PMID- 15489577
TI  - Infliximab for acute, not steroid-refractory ulcerative colitis: a randomized
      pilot study.
AB  - OBJECTIVE: Therapeutic alternatives for patients with acute ulcerative colitis in
      whom steroids would usually be contraindicated are rare. The antibody to tumor
      necrosis factor alpha, infliximab, has shown to be effective in the treatment of
      steroid-refractory ulcerative colitis in pilot studies. We therefore evaluated
      whether infliximab can achieve remission in patients with acute ulcerative
      pancolitis who were not steroid-refractory. METHODS AND DESIGN: Patients were
      eligible if they had acute disease with a modified Truelove and Witts activity
      score of more than 10 for at least 2 weeks and if they were currently not
      receiving immunomodulators or more than 10 mg/day prednisolone. Patients were
      randomly assigned to receive either three intravenous infusions of infliximab at
      5 mg/kg (group A) or high-dose prednisolone (1.5 mg/kg body weight) daily for 2
      weeks, followed by 1 mg/kg for 1 week, followed by a weekly reduction of 5 mg
      (group B). Therapy success was defined as clinical response in terms of a
      decrease of more than 5 points from the baseline score and to less than 10 points
      total after 3 weeks as well as after 13 weeks. RESULTS: Thirteen patients (seven
      women, six men) were randomized (six for group A and seven for group B). The
      median baseline activity scores were 13.5 (12-18) in group A and 14.0 (11-18) in
      group B. Five of six patients in group A and six of seven patients in group B
      showed therapy success after 3 weeks as well as after 13 weeks. CONCLUSIONS:
      Infliximab could be effective in the treatment of acute moderate or severe
      ulcerative colitis. The obtained data call for larger controlled trials.

PMID- 15489578
TI  - The short-term effects of Eudragit-L-coated prednisolone metasulphobenzoate
      (Predocol) on bone formation and bone mineral density in acute ulcerative
      colitis.
AB  - BACKGROUND: The aetiology of bone loss in ulcerative colitis is multifactorial,
      but corticosteroid treatment is an important risk factor. A novel formulation of
      Eudragit-L-coated prednisolone metasulphobenzoate (Predocol) has been developed,
      in order to deliver high mucosal levels of prednisolone within the colon but with
      little systemic absorption. The aim of this study was to investigate its
      efficacy, and short-term effects on bone formation and bone mineral density.
      METHODS: In a 12-week longitudinal study 13 patients with active colitis were
      treated with a reducing dose of Predocol. Disease activity scores were recorded
      and the bone formation marker osteocalcin was measured before, during and after
      treatment, with hip and spine bone mineral density assessed at baseline and after
      treatment. RESULTS: Eleven of the 13 patients completed the study. Compared with
      baseline, disease activity scores improved significantly after 4 weeks
      [difference in means, 6.9; 95% confidence interval (CI), 5.2, 8.7; P < 0.0001]
      and 12 weeks (difference in means, 5.7; 95% CI, 3.3, 8.2; P < 0.0001) of
      treatment. Osteocalcin did not fall compared with baseline [16.91 mg/l (95% CI,
      12.70, 21.12)], after 4 weeks [13.67 mg/l (95% CI, 8.72, 18.60)] (difference in
      means, 3.25; 95% CI, 2.37, 8.87; P = 0.23) or 12 weeks [23.91 mg/l (95% CI,
      16.10, 31.74)] (difference in means, 13.23; 95% CI, 2.45, 16.48; P = 0.13) of
      treatment. Similarly, bone mineral density at the hip [0.99 g/cm (95% CI, 0.90,
      1.09)] did not change after 12 weeks of treatment [1.00 g/cm (95% CI, 0.89,
      1.11)] (difference in means, 0.01; 95% CI, 0.25, 0.34; P = 0.74). Spine bone
      mineral density did not fall from pre-treatment levels [1.20 g/cm (95% CI, 1.11,
      1.30)] after 12 weeks [1.19 g/cm (95% CI, 1.10, 1.29)] (difference in means,
      0.01; 95% CI, 0.004, 0.01; P = 0.26). CONCLUSIONS: These results confirm that
      Predocol is effective treatment for acute ulcerative colitis and short courses of
      the steroid have no adverse effects on bone formation and bone mineral density.
      The encouraging results from this study suggest that Predocol may be a
      significant advance in preventing corticosteroid induced bone loss in ulcerative
      colitis.

PMID- 15489579
TI  - Association of NOD2/CARD15 variants with Crohn's disease in a Greek population.
AB  - OBJECTIVE: Single nucleotide polymorphisms in the NOD2/CARD15 gene have recently
      been shown to be associated with Crohn's disease (CD), but whether this
      susceptibility extends to all ethnic groups and geographic areas remains unknown.
      The aim of the present study was to evaluate the NOD2/CARD15 mutations in Greek
      patients with CD. METHODS: Individuals were genotyped for three NOD2/CARD15
      mutations: R702W, G908R and L1007fsinsC. Blood samples were obtained from 120
      patients with CD, 85 patients with ulcerative colitis, and 100 unrelated healthy
      controls. RESULTS: Mutations in NOD2/CARD15 were observed with significantly
      greater frequency in CD patients (98/120, 81.7%) than in ulcerative colitis
      patients (40/85, 47%) (P < 0.0001) or in healthy individuals (21/100, 21%) (P <
      0.0001). For CD patients, compared with controls, the odds were increased for
      carriage of the R702W (odds ratio, 12.25) and less for the G908R (odds ratio,
      5.2) and L1007fsinsC (odds ratio, 3.9) mutations. The age of onset of CD was
      lower in Greek mutation carriers as compared with non-carriers of Greek origin
      (28.2 +/- 14.6 years versus 34 +/- 12.3 years, respectively; P = 0.036).
      Additionally, the frequency of NOD2/CARD15 mutations was increased in ileitis or
      ileocolitis compared with non-ileal disease. CONCLUSIONS: The NOD2/CARD15
      mutations are risk factors for CD in Greece, they appear to predict an earlier
      age of onset and are associated particularly with ileitis or ileocolitis.

PMID- 15489580
TI  - Histological changes in the gastric mucosa after Helicobacter pylori eradication.
AB  - BACKGROUND AND AIM: Correa described a stepwise model of changes in the gastric
      mucosa after Helicobacter pylori infection, from the normal gastric epithelium to
      chronic gastritis, atrophy, intestinal metaplasia, dysplasia and adenocarcinoma.
      The aim of this study is to assess the reversibility of these mucosal changes
      after H. pylori eradication. METHODS: The study sample consisted of 89 patients
      who underwent at least two gastric biopsies from 1990 to 2000, with a positive
      finding for H. pylori in the first and a negative finding in the second.
      Specimens were evaluated for acute and chronic inflammation, lymphoid aggregates,
      proliferation, mucosal atrophy, intestinal metaplasia, dysplasia, and MUC5AC and
      MUC6 expression using histochemical and immunohistochemical methods. RESULTS: The
      average time between biopsies was 23.15 +/- 26.30 months. There was a significant
      decrease in acute and chronic inflammation scores, from 1.48 +/- 1.10 to 0.23 +/-
      0.63 and from 2.67 +/- 0.68 to 1.44 +/- 1.04, respectively (P < 0.001), and in a
      number of lymphoid follicles, from 42.68% to 21.95% of cases (P < 0.008). The
      number of glands increased from 39.08 +/- 16.67/mm to 48.86 +/- 17.93/mm after
      eradication (P = 0.062). Intestinal metaplasia was found in 17.07% of the cases,
      with no change over time. Dysplasia appeared in one case 2 years after
      eradication. In 27 patients, the Ki67 labeling index decreased significantly
      after eradication, while MUC5AC and MUC6 expression increased. CONCLUSION: Our
      findings, although not conclusive for arrest of the malignant potential, support
      the importance of H. pylori eradication in the prevention of gastric cancer.

PMID- 15489581
TI  - Diagnosis and grading of gastritis by non-invasive optical analysis.
AB  - OBJECTIVES: The precise identification of many diseases of the gastrointestinal
      tract requires the histological analysis of multiple biopsies of the lining
      mucosae, thus preventing an immediate diagnosis and the safe screening of the
      entire organ. To address these limitations, we developed a novel spectroscopic
      procedure for a real-time, non-invasive optical analysis of mucosae. METHODS: We
      have used a fibre-optic probe that monitors light propagation through small
      tissue volumes to evaluate the antral and fundic mucosa of 51 patients that
      underwent gastroscopy for symptoms of dyspepsia. Several optical coefficients
      were computed from the recorded light reflectance, and confronted to the
      diagnosis made by an expert gastroscopist at the time of the clinical
      examination. Both evaluations were then validated by comparison with the
      histological diagnosis of a pathologist who screened biopsies taken at the sites
      of the optical measurements. RESULTS: We report that the optical procedure
      discriminated normal and pathological gastric mucosae with a higher sensitivity
      and specificity than endoscopic diagnosis. We also show that the changes in light
      scattering coefficient, which permitted the optical diagnosis of gastritis
      alterations, were indirectly correlated with the extent of inflammatory
      infiltration of the mucosa and detected mucosal alterations mild enough to escape
      endoscopic detection. CONCLUSIONS: The results show that, in a normal clinical
      setting, the optical in vivo analysis provided by our system detects alterations
      typical of gastritis, and allow for their graded scoring with a specificity and
      sensitivity that compare well with those of standard histology, while avoiding
      the invasiveness of the latter procedure. The method is adaptable to the
      screening of other types of lesions and mucosae and, hence, should prove useful
      in improving available diagnostic approaches.

PMID- 15489582
TI  - In vitro 1H-magnetic resonance spectroscopy of Barrett's esophageal mucosa using
      magic angle spinning techniques.
AB  - OBJECTIVES: In vitro proton magnetic resonance spectroscopy (MRS) allows changes
      in cell membrane lipid structure associated with dysplasia and malignant
      transformation to be investigated. Magic angle spinning (MAS) MRS allows small
      esophageal tissue specimens to be studied directly without the need to extract
      the tissue, but it is not known how intact the tissue architecture remains after
      MAS. We report the first prospective MAS MRS study of Barrett's esophagus using
      endoscopic biopsies with direct histological correlation. METHODS: Biopsies were
      obtained during surveillance esophagoscopy from Barrett's epithelium and adjacent
      normal squamous epithelium in 16 patients (34 samples). High-resolution MAS MRS
      was performed at 500 MHz. Following MRS, the histology was evaluated. A further,
      separate group of 14 biopsies were examined histologically to assess
      architectural damage caused by tissue preservation alone. RESULTS: For squamous
      and Barrett's epithelium, respectively, metabolite ratios of choline-containing
      compounds to creatine plus phosphocreatine (Cho/Cr) were 1.99 and 5.65 (P < 10)
      and methyl lipid to creatine plus phosphocreatine ratios (lipid-CH3/Cr) were 4.07
      and 7.4 (P < 10). There was no significant difference in histological
      preservation between the squamous and Barrett's mucosa without MRS (z = 0.67, P =
      0.61), but significant differences were found post-MAS MRS (z = 4.06, P <
      0.0001). CONCLUSIONS: Squamous and Barrett's epithelium can be distinguished
      metabolically, based on Cho/Cr and lipid-CH3/Cr ratios. Although MAS does affect
      the histological architecture in Barrett's epithelium, compared with squamous
      epithelium, direct histological assessment was possible in the majority of
      samples.

PMID- 15489583
TI  - Recurrent hepatitis C genotype 1b following liver transplantation: treatment with
      combination interferon-ribavirin therapy.
AB  - BACKGROUND: Recurrent hepatitis C is very common leading to graft cirrhosis in a
      significant proportion of patients. Preliminary reports of combination therapy
      with interferon-ribavirin have been promising but generally applied to selected
      patients with chronic mild disease. Little is known, however, about the efficacy
      and risk of adverse effects when it is used in general clinical practice. AIMS:
      To analyse the efficacy (biochemical, virological and histological response) and
      tolerance of combination therapy in patients with recurrent hepatitis C genotype
      1b. METHODS: Twenty-four patients (mean age 54 years; range 37-67 years; 75%
      male) with recurrent hepatitis C virus (histology at baseline: acute hepatitis (n
      = 3); chronic hepatitis (n = 21) with F3 or 4 in 77%) were treated with 12 months
      interferon (1.5-3 MU thrice weekly) + ribavirin (600-1200 mg daily) followed by 6
      months ribavirin (58%), at a median of 427 days (56-2812) after transplantation.
      RESULTS: Seven patients (29%) discontinued therapy due to side effects, mainly
      anaemia, at a median of 3 months since initiation. Dose modifications were
      required in 88% of those completing the whole course of therapy. Overall, the
      sustained virological and biochemical response was 12.5%. This rate was slightly
      higher (18%) if only the 17 patients who finished the whole course of therapy
      were analysed. Histological improvement was achieved in 31.5% of treated
      patients. CONCLUSIONS: Combination therapy has a very limited efficacy in the
      liver transplant setting, although some benefit may be achieved, even in those
      with advanced graft fibrosis. Tolerance, however, remains a matter of concern.

PMID- 15489584
TI  - Correlation of quantitative assay of hepatitis B surface antigen and HBV DNA
      levels in asymptomatic hepatitis B virus carriers.
AB  - OBJECTIVE: This study was to elucidate the correlation between quantity of
      hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA levels in
      asymptomatic carriers. METHODS: Based on the presence of the hepatitis B e
      antigen (HBeAg) and HBV DNA levels, 67 asymptomatic carriers were divided into
      four groups. HBV DNA was determined by hybridization (sensitivity 141 500
      copies/ml) and polymerase chain reaction (PCR, sensitivity < 10 copies/ml). Cases
      of groups I (n = 18), II (n = 17) and III (n = 16) were negative for HBeAg and
      had HBV DNA levels of < 10 (PCR undetectable), 10 to 10 (PCR detectable) and > 10
      copies/ml (hybridization detectable), respectively. Cases of group IV (n = 16)
      were positive for HBeAg and high HBV DNA levels (> 2 x 10 copies/ml). HBsAg was
      determined quantitatively by the ARCHITECT HBsAg assay. RESULTS: Our data showed
      HBsAg levels were correlated with HBV DNA (r = 0.709; P < 0.001) on a log scale.
      The mean log HBsAg (IU/ml) of groups I, II, III and IV were 2.68 +/- 0.8, 2.93 +/
      1.03, 3.22 +/- 0.45, 4.83 +/- 0.19, respectively. That of group IV was
      significantly higher than the mean log HBsAg of any other group (P < 0.001). The
      best cut-off for HBsAg in differentiating group IV from other groups was 15 000
      IU/ml with both sensitivity and specificity of 100%. That of group I was
      significantly lower than those of group III (P = 0.035) and IV (P < 0.001). The
      best cut-off in differentiating group I from the other groups was 1600 IU/ml with
      a sensitivity of 69.4% and a specificity of 66.7%. CONCLUSION: Quantitative
      measurement of HBsAg titres may be an easy and economical reference for HBV
      replication in HBV carriers.

PMID- 15489585
TI  - Histological response in patients treated by interferon plus ribavirin for
      hepatitis C virus-related severe fibrosis.
AB  - BACKGROUND: Studies of viral hepatitis C have suggested that fibrosis can
      regress, at least in patients with sustained virological response. A recent study
      suggested that cirrhosis was reversible in sustained and non-virological
      responders. AIM: To study fibrosis progression rate and cirrhosis reversion in
      patients treated for severe fibrosis with interferon or interferon + ribavirin.
      PATIENTS AND METHODS: Ninety-nine patients were treated with interferon +
      ribavirin and 64 with interferon. The Metavir fibrosis score and the
      semiquantitative fibrosis score (SFS) were used to assess fibrosis. RESULTS: In
      sustained responders, fibrosis progression rate decreased from 0.26 Metavir unit
      (interquartile range: 0.19-0.34) to -0.67 (-0.67 to 0) (P < 0.0001) and from 0.81
      SFS unit (0.48-1.13) to -1.33 (-3.67 to 0) (P < 0.0001). In non-responders,
      fibrosis progression rate decreased from 0.25 Metavir unit (0.17-0.33) before
      treatment to 0 (0-0) during treatment (P = 0.002) and from 0.63 SFS unit (0.49
      1.12) to 0 (-2.67-1.33) (P = 0.18). Six out of 18 (33%) sustained virological
      responders and four of 43 (9%) non-responders regressed from cirrhosis (F4) to
      severe fibrosis (F3) (P = 0.058). No patient with cirrhosis had a decrease of
      Metavir fibrosis score of 2 points. CONCLUSION: Interferon can slow fibrosis
      progression in sustained virological responders with severe fibrosis. In patients
      with a non-virological response and treated for 12 months the fibrosis
      progression rate was nil, meaning that only fibrosis stabilization could be
      obtained in these patients. Then, longer treatment duration (3-4 years) could be
      evaluated in non-virological responders.

PMID- 15489586
TI  - Does cooling Sengstaken-Blakemore tubes aid insertion? An evidence based
      approach.
AB  - OBJECTIVE: To survey current clinical practice concerning the use of Sengstaken
      Blakemore (SB) tubes and to determine whether cooling the tubes alters their
      stiffness. METHODS: A telephone questionnaire was conducted of gastroenterology
      registrars and ITU departments in the North Thames region. The current clinical
      practice for insertion of SB tubes and the basis for this practice were
      determined in each case. The stiffness of the tubes was measured at -10 degrees C
      and 20 degrees C by measuring the extension (in mm) resulting from an applied
      load (in newtons). The time for tube warming from -30 degrees C when in
      stationary air and when in contact with skin was also recorded. RESULTS: Fifty
      registrars were contacted and 20 ITU departments were surveyed. All ITU
      departments involved the gastroenterologists in the management of acute variceal
      bleeds. Eight registrars had never placed an SB tube. The majority of the
      remainder (95%) used a cooled SB tube. All of the registrars based this practice
      upon their clinical teaching, and 75% of these registrars thought cooling aided
      the insertion of the tube. There was no significant difference in the stiffness
      of the tubes at -10 degrees C and 20 degrees C. Upon warming, an SB tube took 30
      s to rise from 0 degrees C to room temperature (20 degrees C) when in skin
      contact and 120 s when placed in stationary air. CONCLUSION: The current clinical
      practice of trainees for the insertion of SB tubes is to cool the tubes in the
      belief that this 'standard' practice aids tube insertion. We found no significant
      change in SB tube stiffness even after cooling to temperatures that would not be
      achieved during routine insertion. Furthermore, the rapid rise in tube
      temperature means that tubes approach room temperature by the time they reach the
      bedside. In the present era of evidence based medicine the current dogma that SB
      tubes should be cooled prior to insertion must be discarded.

PMID- 15489587
TI  - Review of surgical management of cystic hydatid disease in a resource limited
      setting: Turkana, Kenya.
AB  - OBJECTIVE: Cystic hydatid disease is a zoonotic infection of humans caused by
      infection with the larval stage of Echinococcus granulosus. The prevalence rate
      (5-10%) in Turkana, Northern Kenya is among the highest worldwide. With an
      increase in foreign travel and migration of peoples, practitioners need to be
      aware of diseases common in these countries and their rarer manifestations. The
      objective of this study was to review the management of this disease in a poorly
      resourced high-prevalence area. METHODS: The surgical records of Kakuma Mission
      Hospital, Turkana from July 1981 to May 2002 were reviewed. RESULTS: A total of
      710 (female : male, 3 : 2) surgical procedures for hydatid disease were recorded,
      the average age being 27 years (range, 3-65 years). There were 663 patients, and
      therefore 47 patients had repeat procedures. A total of 52.8% (n = 375) had
      hepatic cysts (248 right sided, 30 left sided, 97 site undefined), and 10.1% (n =
      72) had multiple abdominal cysts. Other intra-abdominal sites included 8.16%
      mesenteric (n = 58), 2.9% retroperitoneal (n = 21), 3.5% spleen (n = 25), the
      abdominal wall (n = 4). There was no information on the site of disease in 5.9%
      of cases (n = 42). More unusual sites were retro-orbital, gluteal, zygomatic,
      brachial, parotid, uterine, tibial and foot. The largest volume of cyst fluid was
      7 l. There was one intraoperative death and one postoperative death recorded.
      Endocystectomy +/- a scolicidal was the commonest procedure performed. However,
      165 percutaneous aspiration injection of a scolicidal agent and reaspiration
      procedures were performed, six being on pregnant women. This is one of the
      largest series of surgical hydatid patients from Africa and demonstrates the wide
      diversity in cyst location.

PMID- 15489588
TI  - Combined liver transplantation plus imatinib for unresectable metastases of
      gastrointestinal stromal tumours.
AB  - Therapeutic options for treating unresectable hepatic metastases of
      leiomyosarcomas were scarce until a few years ago. Recent advances in the study
      of the biology of intestinal tumours have radically changed our knowledge of
      their pathogenesis. Many of the tumours previously considered as leiomyosarcomas
      are now identified as gastrointestinal stromal tumours (GISTs). The introduction
      of imatinib (an antineoplasic drug that specifically acts on the pathogenesis of
      these tumours) has shown promising results in patients with advanced GISTs. We
      present three patients with the initial diagnosis of unresectable hepatic
      metastases of leiomyosarcomas. They received liver transplants. All three had
      tumour recurrences after transplantation. Histological re-evaluation identified a
      stromal origin of the tumours, and the patients were treated with imatinib
      therapy (400 mg/day). Recurrence occurred in all patients after a mean of 38.3
      months, but imatinib treatment achieved control of the tumours. The current
      survival times with the combination of transplantation and imatinib are 92, 48
      and 46 months for the three patients. This series is small and inconclusive, but
      imatinib treatment showed promising results. The treatment options for patients
      with unresectable metastases of GISTs must be defined, as in these three patients
      liver transplantation achieved a disease-free status but all had tumour
      recurrences before starting the imatinib treatment.

PMID- 15489589
TI  - Acute pulmonary embolism: a rare complication of a large non-parasitic hepatic
      cyst.
AB  - A 56-year-old patient with a non-parasitic hepatic cyst developed acute dyspnoea.
      Pulmonary embolism was diagnosed. Bleeding into the hepatic cyst, leading to its
      enlargement and compression of the inferior vena cava, was the only likely cause
      of the pulmonary embolism. This complication of a non-parasitic liver cyst has
      not been reported previously. The patient was treated with heparin. Surgical
      evacuation of the cyst using the 'fenestration' technique was also performed.
      There was no recurrent pulmonary embolism or hepatic cyst during a 1-year follow
      up period.

PMID- 15489590
TI  - Critical intestinal ischaemia in a patient with patent mesenteric vasculature.
AB  - We present a case of a 62-year-old man with known coeliac disease who was
      admitted for investigation of abdominal pain and weight loss. He underwent
      multiple biochemical, haematological, radiological and endoscopic investigations
      (which were all normal) and also had a normal laparoscopy. Abdominal computerized
      tomography angiography, however, suggested significant mesenteric stenosis.
      Mesenteric angiography confirmed superior mesenteric artery stenosis and
      reproduced the patient's abdominal pain when the catheter crossed the lesion.
      Balloon angioplasty successfully dilated the stenosis, and since then the patient
      has gained 19 kg in weight (returning his body mass index from 17 to 23) and has
      been symptom free. Symptomatic single vessel mesenteric ischaemia (other than
      coeliac artery stenosis in median arcuate syndrome) is not previously well
      described. The symptom reproduction on catheterization highlights how useful
      angiography can be in diagnosis of disease significance. Symptom resolution after
      angioplasty demonstrated clearly how even single vessel disease can cause
      significant compromise to the mesenteric circulation.

PMID- 15489602
TI  - Muscle up your knowledge of myocarditis.

PMID- 15489606
TI  - Collecting umbilical cord blood.

PMID- 15489607
TI  - Using insulin to prevent hyperglycemia in surgical patients.

PMID- 15489608
TI  - Assessing pain in patients who can't communicate.

PMID- 15489614
TI  - Can my patient breast-feed after surgery?

PMID- 15489621
TI  - Julie's bath.
AB  - Performed with a dose of kindness, a humble nursing task becomes something out of
      the ordinary.

PMID- 15489626
TI  - Keeping catheters clear with low-dose warfarin.

PMID- 15489628
TI  - Myths and facts...about autism.

PMID- 15489629
TI  - Tracheostomy mucus plug.

PMID- 15489630
TI  - The role of the mitochondrion in trauma and shock.
AB  - The mitochondrion of the eukaryotic cell is well known as a "power plant" whose
      energy is made available via the high-energy phosphate bonds of ATP. This
      indispensable and superbly adapted organelle appears to have originated as an
      endosymbiotic bacterium rather than as a eukaryotic creation per se. However,
      under the dangerous conditions of trauma and shock, the mitochondrion can become
      destabilized and harm its host cell in a variety of ways. These contrary traits
      may be, in part, vestiges from the bacterial origins of mitochondria. The
      mitochondrion can respond to the stress of trauma and shock by opening pores that
      leak contents into the host cell's cytoplasm, an event that can trigger
      programmed cell death or necrosis. In addition, the enormous oxygen consumption
      by mitochondria presents a two-edged sword in that a deranged mitochondrion can
      produce reactive oxygen species that damage genes and gene products, inflicting
      considerable harm to the mitochondrion and its host cell. However, although
      trauma and shock can cause the mitochondrion to wreak havoc in many ways, an
      adjuvant intervention with exogenous ATP-MgCl2 after trauma and shock appears
      useful for reducing cell and organ damage under those conditions.

PMID- 15489631
TI  - Increased expression of toll-like receptor-2 and -4 on leukocytes from patients
      with sepsis.
AB  - The reduced responsiveness of monocytes or granulocytes toward endotoxin
      (endotoxin tolerance) during sepsis may depend on Toll-like receptors (TLR). The
      expression of TLR-2 and TLR-4 was measured on neutrophils (PMN) and monocytes
      from patients with sepsis (n = 21) or healthy controls (n = 12). Leukocytes (1 x
      10/mL) were incubated at 37 degrees C with or without a TLR-4 (LPS 1 microg/mL)
      or a TLR-2 ligand (MALP-2 2 nM). Surface expression of TLR-2 and TLR-4 at 0, 4,
      and 16 h was determined in FACS after staining with specific antibodies. The
      release of IL-8 and TNF-alpha was measured by ELISA. Freshly isolated PMN from
      patients with sepsis exhibited significantly (P < 0.05) higher mean fluorescence
      for TLR-2 (78.0 +/- 18.6) and TLR-4 (11.4 +/- 2.3) than controls (12.8 +/- 2.2
      and 2.3 +/- 0.4). Similarly, monocytes from patients exhibited higher TLR-2 and
      TLR-4 expression (300.8 +/- 40.6 and 92.7 +/- 12.1) than cells from controls
      (149.5 +/- 27.1 and 52.2 +/- 7.6). In patients with sepsis, expression of TLR-2
      and TLR-4 on PMN increased during 16 h of incubation (106.2 +/- 22.1 and 34.5 +/-
      5.3), whereas it remained unchanged in controls (19.3 +/- 6.1 and 5.4 +/- 1.9).
      Incubation with LPS or MALP-2 had no effect on TLR-4 or TLR-2 expression in cells
      from either controls or patients. Despite increased TLR expression in cells from
      patients with sepsis, the endotoxin-induced release of TNF-alpha and IL-8 was
      indistinguishable from that in controls. Therefore, the endotoxin tolerance seen
      in patients with sepsis does not depend solely on TLR-2 or TLR-4 expression, and
      other mechanisms must be involved.

PMID- 15489632
TI  - Severity of emergency department hypotension predicts adverse hospital outcome.
AB  - Arterial hypotension often signifies inadequate systemic perfusion. We
      hypothesize that in a heterogeneous emergency department (ED) population with
      clinically suspected circulatory shock, the severity of hypotension on
      presentation predicts in-hospital outcome. We performed a secondary analysis of
      patients with nontraumatic shock enrolled in a noninterventional, randomized,
      controlled trial. The setting was an urban, tertiary ED, census >100,000 visits
      per year. Patients included nontrauma ED patients, aged >17 years, with initial
      ED vital signs consistent with shock (systolic blood pressure <100 mmHg or shock
      index >1.0), and agreement of two independent observers for at least one sign and
      symptom of inadequate tissue perfusion. Measurements included interobserver
      agreement for signs and symptoms of shock, relationship between the depth and
      duration of ED hypotension and adverse hospital outcome (in-hospital mortality,
      need for intensive care unit services, and acute organ failure) and logistic
      regression analysis for independent predictors of adverse hospital outcome. Of
      202 patients who qualified, 190 patients were included; the in-hospital mortality
      rate was 15%. The sign or symptom of shock with the highest interobserver
      agreement was "unresponsive" (kappa = 0.74). The adverse hospital outcomes
      increased with each decile decrease in the lowest ED systolic blood pressure
      (SBP) from 17% if SBP >89 mmHg versus 50% if SBP < 80 mmHg. Forty percent of
      patients with an adverse hospital outcome had sustained hypotension (all ED SBP
      <100 mmHg for > or =60 min). Sustained hypotension was the strongest independent
      predictor of an adverse hospital outcome (odds ratio 3.1; 95% CI 1.5-7.1).
      Mortality among patients who present to the ED with undifferentiated shock is
      high. The depth and duration of systolic blood pressure appears to have a dose
      response relationship to adverse hospital outcome.

PMID- 15489633
TI  - A theoretical simulation of hematopoietic stem cells during oxygen fluctuations:
      prediction of bone marrow responses during hemorrhagic shock.
AB  - The bone marrow (BM) responds to various diseases, including infections and
      hemorrhagic shock, by generating immune and blood cells. These cells are derived
      from a finite number of lymphohematopoietic stem cells (LHSC) close to the
      endosteal region of the BM. This study presumes that studies on LHSC involving
      proteomics, computational biology, and genomics could be aided by mathematical
      models. A theoretical model is developed to predict the responses of
      proliferating (P) nonproliferating (N) BM cells during acute blood loss when the
      Po2 in the BM is decreased. Hematopoietic responses were simulated for otherwise
      healthy individuals who have been subjected to various degrees of blood loss, as
      represented by 3%, 5%, and 20% O2. The model is robust and could predict
      hematopoietic activity in the area close to the endosteum during low Po2 as for
      acute blood loss. Steady-state hematopoiesis at oxygen saturation (80%) in
      healthy individuals could not be simulated with the equations. Functional assays
      tested the model with an in vitro assay of the most primitive LHSC (modified long
      term culture-initiating cell assay, LTC-IC). The LTC-IC assay showed that 1%, 3% 
      5%, and 20% O2 mediate significant increases in the proliferation of the most
      primitive BM progenitors, as compared with 80% O2. Thus, the functional studies
      show that the theoretical model is robust and could be used to gain insights into
      the biology of LHSC during different degrees of blood loss. The utility of such a
      model in surgical trauma is discussed.

PMID- 15489634
TI  - Infection-induced modulation of m1 and m2 phenotypes in circulating monocytes:
      role in immune monitoring and early prognosis of sepsis.
AB  - To monitor and better understand the immunoinflammatory sequelae in sepsis and
      septic shock, systemic and monocyte-related cytokine responses were evaluated in
      baboons with experimental peritonitis induced by an E. coli-laden fibrin clot.
      Despite similar bacterial inocula, considerable interindividual variability in
      clinical manifestation and outcome of infection was observed. Because monocytes
      and macrophages are a key component of innate immunity, we hypothesized that
      early polarization of distinct activation programs in circulating monocytes that
      culminates in the emergence of either classically (M1) or alternatively (M2)
      activated monocytes may underlie the observed susceptibility or resistance to
      infection. To test our hypothesis, we analyzed infection-induced expression of
      cytokine mRNAs in monocytes isolated from surviving and dead animals. Our data
      show that resistance to E. coli sepsis may well be associated with a mixed M1/M2
      activation state of circulating monocytes, whereas M1 phenotype appeared to be
      prevailing in monocytes from animals that died. Together with data on systemic
      cytokine responses, the latter findings indicate that morbidity and mortality of
      animals with gram-negative sepsis may well result from an overwhelming
      proinflammatory response. Collectively, our data contribute to a better
      understanding of cytokine networking in the immunoinflammatory response to
      microbial infection and suggest M1/M2 immunophenotypic profiling of readily
      available circulatory monocytes for early prognosis of severe infections.

PMID- 15489635
TI  - Hyperosmotic-hyperoncotic versus hyperosmotic-hyperviscous: small volume
      resuscitation in hemorrhagic shock.
AB  - The aim of this study was to test the effects of using a high-viscosity fluid
      after small-volume hyperosmotic resuscitation from hemorrhagic shock and to
      compare this to hyperosmotic followed by hyperoncotic resuscitation. Studies were
      made in the awake hamster window chamber preparation with the animals subjected
      to hemorrhage of 50% of blood volume and resuscitated with a small volume of a
      7.5% NaCl solution, which was followed within minutes by infusion of 25% of
      withdrawn volume of either 0.7% or 0.8% alginate solutions (A0.7%, 7.6 cp; and
      A0.8%, 10.2 cp) or 5% hydroxyethyl starch (HES 5%, 2.1 cp). All modalities of
      resuscitation returned blood pressure to near baseline values in 5 min, which
      remained elevated after 90 min with A0.7% and A0.8% but returned to near shock
      values in 15 min with HES 5%. Microvascular flow and functional capillary density
      (FCD) followed the same pattern, being significantly higher for the alginate
      solutions than HES 5% after 90 min. Plasma viscosity 90 min after resuscitation
      was 2.1 and 2.6 cp for A0.7% and A0.8%, respectively, and 1.1 cP for HES 5%.
      There was an apparent directly proportional relationship between the
      concentration of alginate and blood pressure recovery, with blood pressure near
      normal with A0.8%, and approximately 20 mmHg lower with A0.7%. The recovery of
      microvascular flow and FCD, although showing a trend toward being more effective
      with A0.8%, was not significantly different from A0.7% but statistically
      different and improved relative to HES 5%. The high-viscosity fluids provide a
      novel small-volume method of resuscitation that maximizes microvascular perfusion
      for extended periods until surgical control of bleeding is possible. Results show
      that high-plasma-viscosity resuscitation provides a more consistent and prolonged
      resuscitation than hyperoncotic treatment. The increase in viscosity presents a
      gradual recovery in blood pressure and may be used as an alternative for small
      volume hypotensive resuscitation, increasing tissue perfusion while potentially
      limiting hemorrhage in vascular injuries of the major blood vessels.

PMID- 15489636
TI  - Effects of burn serum on myocardial inflammation and function.
AB  - Large cutaneous burns are clearly recognized to produce acute myocardial
      contractile dysfunction. This study used a model of burn serum challenge in
      either primary cardiomyocyte cultures or isolated perfused hearts to examine
      several aspects of burn-serum-related contractile dysfunction as well as
      myocardial inflammatory responses. Despite the absence of detectable LPS in burn
      serum, pretreating isolated cells or perfused hearts with recombinant
      bactericidal permeability-increasing protein (rBPI21) prevented both the
      inflammatory cytokine cascade and the cardiac contractile dysfunction induced by
      burn serum treatment of myocytes or ventricular muscle preparations. Our finding
      that anti-TNF strategies applied to isolated myocytes or hearts before burn serum
      challenge prevented myocardial inflammation and contractile dysfunction suggested
      that LPS or LPS-like factors may require the action of second messengers such as
      TNF-alpha and IL-1beta to mediate LPS-related myocardial depressant effects. Our
      finding that experimental approaches neutralizing circulating LPS provided
      cardioprotection suggested that bacterial endotoxin or LPS-like molecules
      contribute, in part, to burn-related myocardial contractile dysfunction.

PMID- 15489637
TI  - Butyrate suppresses hypoxia-inducible factor-1 activity in intestinal epithelial
      cells under hypoxic conditions.
AB  - Interaction between the products of intestinal bacteria and the intestinal
      epithelial cells is a key event in understanding the biological, physiological,
      and pathological functions of the intestinal epithelium. Here, we examined the
      effect of butyrate, one of the major intestinal bacterial products, on hypoxia
      inducible factor-1 (HIF-1) activity under hypoxic conditions in intestinal
      epithelial cells. HIF-1 activity was assessed by luciferase assay using
      cytoplasmic extracts of intestinal epithelial cells, Caco-2, and IEC-6 cells.
      These cells were transiently transfected with hypoxia response element (HRE)
      luciferase reporter plasmids and cultured under hypoxic conditions in the
      presence or absence of sodium butyrate (NaB). The effect of NaB on HRE DNA
      binding activity in Caco-2 cells under hypoxic conditions was assessed by
      electrophoretic mobility shift assay. Expression of a hypoxia-responsive gene
      encoding intestinal trefoil factor (ITF) in Caco-2 cells after NaB treatment was
      assessed using reverse-transcription PCR. The barrier function of Caco-2 cells
      under hypoxic conditions was also evaluated by transepithelial electrical
      resistance measurement. NaB suppressed up-regulation of HIF-1 transcriptional
      activity under hypoxic conditions in Caco-2 and IEC-6 cells. In parallel, NaB
      reduced HRE DNA binding activity under the same conditions. Furthermore, NaB down
      regulated enhanced transcription of ITF gene. Addition of NaB under hypoxic
      conditions delayed recovery of transepithelial electrical resistance of the
      monolayers after hypoxia-reoxygenation treatment. These findings indicate that
      NaB suppresses HIF-1 transcriptional activity on hypoxia-responsive genes by
      reducing the HRE DNA binding activity under hypoxic conditions in intestinal
      epithelial cells.

PMID- 15489638
TI  - Alpha-melanocyte stimulating hormone protects against H2O2-induced inhibition of
      wound restitution in IEC-6 cells via a Syk kinase- and NF-kappabeta-dependent
      mechanism.
AB  - Epithelial injury and repair are central consequences of ischemia and reperfusion
      of the gut. Intestinal mucosal wounds are repaired in part by epithelial
      restitution. However, the signaling mechanisms regulating restitution remain
      poorly understood, and few therapies to enhance restitution have been described.
      Previously we demonstrated that alpha-melanocyte-stimulating hormone (alpha-MSH)
      protected against postischemic gut injury in the rat. In this report, we tested
      the effects and mechanisms of alpha-MSH on wound restitution of rat small
      intestine (IEC-6) cells subjected to H2O2 stress with or without scrape wounding.
      H2O2 treatment resulted in tyrosine phosphorylation of Syk kinase and its
      downstream target IkappaBalpha, with subsequent NF-kappaB activation. Alpha-MSH
      and the Syk kinase inhibitor piceatannol blocked these processes. In scrape
      wounded cells, H2O2 inhibited wound restitution, and this was partially restored
      by cotreatment with alpha-MSH or piceatannol. In contrast, overexpression of NF
      kappaB p65 or Syk kinase, but not a dominant-negative mutant of Syk kinase,
      aggravated H2O2 inhibition of wound restitution, and inhibitors of c-Src tyrosine
      kinase or phosphatidylinositol-3 kinase were without effect. The results indicate
      an important role for Syk tyrosine kinase and the NF-kappaB pathway in the
      response to oxidant stress and the impairment of epithelial restitution in IEC-6
      cells. The data also disclose that the beneficial effects of alpha-MSH on gut
      ischemia/reperfusion injury may relate to its acceleration of epithelial
      restitution.

PMID- 15489639
TI  - Innate immune response in Th1- and Th2-dominant mouse strains.
AB  - C57BL/6 and BALB/c mice are prototypical Th1- and Th2-type mouse strains,
      respectively. In the present study, we attempted to characterize the innate
      immune response of macrophages from these mouse strains. Macrophages from C57BL/6
      mice produced higher levels of tumor necrosis factor-alpha (TNF-alpha) and
      interleukin (IL)-12 than those from BALB/c mice after stimulation with macrophage
      activating lipopeptide-2 (MALP-2, a synthetic TLR-2 ligand) or lipopolysaccharide
      (LPS, a TLR-4 ligand). The augmented IL-12 production by C57BL/6 macrophages
      increased interferon-gamma and, in contrast, decreased IL-13 production by CD4+ T
      cells. On stimulation with MALP-2 or LPS, C57BL/6 macrophages produced lysosomal
      enzyme and nitric oxide, effector molecules for bacterial killing, whereas BALB/c
      macrophages did not. Bactericidal activity of BALB/c macrophages was impaired
      relative to C57BL/6 macrophages when cells were infected with live bacteria in
      vitro. In a murine model of septic peritonitis induced by cecal ligation and
      puncture (CLP), BALB/c mice failed to facilitate bacterial clearance relative to
      C57BL/6 mice despite an augmented peritoneal leukocyte infiltration that was
      associated with increased peritoneal levels of cytokines/chemokines. BALB/c mice
      exhibited increased plasma and hepatic levels of cytokines/chemokines, resulting
      in an exaggerated systemic inflammation as determined by acute-phase proteins.
      Finally, BALB/c mice were vulnerable to CLP-induced lethality relative to C57BL/6
      mice. Altogether, innate immune response of macrophages is different between
      these mouse strains, which may affect the development of Th1 and Th2 adaptive
      immunity in these strains. Reduced systemic inflammatory response in C57BL/6 mice
      that may result from an eminent local response appears to be beneficial during
      sepsis.

PMID- 15489640
TI  - Pancreatic proteases and inflammatory mediators in peritoneal fluid during
      splanchnic arterial occlusion and reperfusion.
AB  - Pancreatic enzymes in the ischemic intestine are involved in the production of in
      vivo inflammatory mediators. These mediators stimulate cells in the
      cardiovascular system during shock and initiate multiorgan failure. An important
      aspect that controls the extent of the inflammation is the dispersion of these
      mediators from the ischemic intestine. In the past, two pathways for dispersion
      of these inflammatory mediators have been identified, absorption into the
      intestinal venous circulation and uptake into the lymphatics. We hypothesize here
      that the inflammatory mediators produced by pancreatic digestive enzymes in the
      lumen of the intestine may also be released directly into the peritoneal space.
      To assess the presence of inflammatory mediators in the peritoneal cavity in
      response to splanchnic arterial occlusion (90 min) and reperfusion (SAO shock),
      we measured the ability of fluid collected from this cavity to activate naive
      donor granulocytes. After SAO in control rats, peritoneal lavage fluid caused
      activation of naive donor granulocytes when tested in vitro. In contrast, when
      the lumen of the small intestine was flushed with a broad-acting pancreatic
      enzyme inhibitor (6-amidino-2-naphtyl p-guanidinobenzoate dimethanesulfate), the
      fluid no longer caused leukocyte activation. Reduction of the levels of
      inflammatory mediators in the peritoneal fluid was associated with an attenuation
      in the fall of blood pressure after SAO shock. These results indicate that the
      inflammatory mediators, which are produced by pancreatic digestive enzymes, can
      be absorbed directly into the systemic circulation via a transperitoneal route
      and play a part in the development of multiorgan failure.

PMID- 15489641
TI  - Inducible nitric oxide synthase inhibitor reverses exacerbating effects of
      hypertonic saline on lung injury in burn.
AB  - The use of hypertonic saline (HTS) resuscitation in major trauma patients is
      still controversial. The objective of this study is to determine if inhibition of
      inducible nitric oxide synthase (iNOS) to stabilize the endothelial permeability
      and to retain HTS in the vascular space will reverse its exacerbating effect on
      burn-induced lung damage. In Experiment 1, specific pathogen-free (SPF) rats
      underwent 35% total body surface area (TBSA) burn and were resuscitated with 7.5
      mL/kg HTS (7.5% NaCl), 7.5 mL/kg saline, or 50 mL/kg saline (nearly equal sodium
      load as HTS) via femoral veins for 15 min immediately after the burn. In
      Experiment 2, S-methylisothiourea (SMT) (7.5 mg/kg, i.p.) was given immediately
      after the burn to rats from the different groups of Experiment 1. At 8 h after
      the burn, the permeability and myeloperoxidase (MPO) activity of lung tissues
      were determined, and plasma samples were assayed for peroxynitrite levels. Burn
      significantly induced lung MPO activity, lung permeability, and blood
      dihydrorhodamine 123 (DHR 123) oxidation in rats. HTS administration after burn
      significantly increased the blood DHR 123 oxidation level, lung MPO activity,
      lung permeability, and inflammatory cell infiltration in comparison with those of
      burn plus 7.5 mg/kg saline and burn plus 50 mL/kg saline rats. In contrast, burn
      plus SMT rats with HTS injection showed significant 54%, 11%, and 35% decreases
      in blood DHR 123 oxidation level, lung MPO activity, and lung permeability,
      respectively, in comparison with burn plus SMT plus 7.5 mg/kg saline rats. In
      conclusion, restoration of extracellular fluid in early burn shock with HTS
      supplementation significantly exacerbates burn-induced lung neutrophil
      deposition, lung hyperpermeability, and blood peroxynitrite production.
      Inhibition of iNOS before HTS supplementation reverses the deteriorating effects
      of HTS on thermal injury-induced lung damage to beneficial ones. Using HTS in
      thermal injury resuscitation without the inhibition of iNOS is dangerous.

PMID- 15489642
TI  - Role of chemically modified tetracycline on TNF-alpha and mitogen-activated
      protein kinases in sepsis.
AB  - Chemically modified tetracyclines are orally active inhibitors of multiple
      proteases and cytokines. In this study, we focused on the regulation of tumor
      necrosis factor (TNF)-alpha and mitogen-activated protein kinases (MAPKs) in
      sepsis and their reduction by treatment with nonantimicrobial chemically modified
      tetracycline-3 (CMT-3), which retains their antiinflammatory activity. Sepsis was
      induced in rats by cecal ligation and puncture (CLP). At 24 h and 1 h before CLP,
      treated rats received CMT-3 (25 mg/kg), and untreated rats received saline by
      gavage. At 0 h, 0.5 h, 1.5 h, and 24 h after CLP, blood and liver samples were
      collected. TNF-alpha was determined by ELISA, and MAPKs were determined by
      Western blot analysis. A significant activation of p38 MAPK was observed after
      0.5 h and 1.5 h of sepsis that appeared to coincide with the increased
      circulating TNF-alpha level. The activation of p42/44 was increased after 24 h of
      sepsis, whereas that of SAPK/JNK was unaltered throughout the course of sepsis.
      CMT-3 pretreatment inhibited the TNF-alpha level as well as p38 MAPK activation
      seen after 0.5 and 1.5 h of CLP and also suppressed the activation of p42/44
      after 24 h post-CLP. These results indicate increased activity of TNF-alpha and
      MAPK following sepsis and demonstrate the beneficial effect of CMT-3 in
      preventing the increase in TNF-alpha, p38 MAPK, p42/44 MAPK, and the progression
      of septic shock.

PMID- 15489643
TI  - Lung effects during a generalized Shwartzman reaction and therapeutic
      intervention with dexamethasone or vitamin E.
AB  - We investigated if a two-hit shock model, commonly referred to as generalized
      Shwartzman reaction (GSR), can prime for indirect acute respiratory distress
      syndrome (ARDS) in mice. The GSR was provoked in C57BL/6 mice by two consecutive
      i.p. injections of 100 microg lipopolysaccharide (LPS) at t = 0 and t = 20 h.
      These mice demonstrated a dramatic decrease in respiratory capacity and 80%
      mortality after the second injection. No such effect was observed when LPS was
      given as a single 200 microg dose at t = 0. Increased expression of
      proinflammatory cytokines in serum (interleukin-1beta, interleukin-6 and
      interferon-gamma), lung neutrophilia, and edema formation were observed in mice
      injected with one dose of LPS, but notably, mice exposed twice did not further
      increase their inflammatory response. Early treatment 1 h after the first LPS
      injection (t = 1 h) with either dexamethasone (10 mg/kg) or vitamin E (50 mg/kg)
      improved respiratory function and down-modulated the induction of proinflammatory
      cytokines in serum. In conclusion, mice with a generalized Shwartzman reaction
      exhibited features resembling some aspects of the pathophysiology in septic ARDS,
      i.e., neutrophilic inflammation, edema formation, impaired respiratory capacity,
      and mortality. Our data indicate that a systemic cytokine response and lung
      neutrophilia may prime for the GSR but that other mechanisms account for the
      rapid decline in lung function after the second challenge. We suggest that this
      model can be used for studies of pathogenesis and therapeutic prevention of acute
      respiratory failure.

PMID- 15489644
TI  - KSHV-positive solid lymphomas represent an extra-cavitary variant of primary
      effusion lymphoma.
AB  - Primary effusion lymphoma (PEL) is a unique form of non-Hodgkin lymphoma (NHL)
      associated with Kaposi sarcoma-associated herpesvirus (KSHV; HHV-8) that displays
      a distinct constellation of clinical, morphologic, immunologic, and molecular
      characteristics. Rare KSHV-containing immunoblastic lymphomas occurring in solid
      tissues have been described. Whether they represent part of the spectrum of PEL
      has not been determined. The morphologic, immunophenotypic, and molecular
      features of KSHV-positive solid lymphomas occurring in 8 HIV+/AIDS patients were
      systematically investigated and compared with those of 29 similarly analyzed
      PELs. The 8 KSHV-positive solid lymphomas were virtually indistinguishable from
      the 29 PELs based on morphology (immunoblastic/anaplastic), immunophenotype (CD45
      positive; T cell antigen negative; CD30, EMA, CD138 positive; CD10, CD15, BCL6
      negative) and genotype (100% immunoglobulin genes rearranged; no identifiable
      abnormalities in C-MYC, BCL6, BCL1, BCL2; and uniformly EBV positive). The only
      identifiable phenotypic difference was that the KSHV-positive solid lymphomas
      appeared to express B cell-associated antigens (25%) and immunoglobulin (25%)
      slightly more often than the PELs (<5% and 15%, respectively; P = 0.11 and P =
      0.08, respectively). The clinical presentation and course of the patients who
      develop KSHV-positive solid lymphomas were also similar, except for the lack of
      an effusion and somewhat better survival (median 11 months vs. 3 months).
      However, the 3 KSHV-positive solid lymphoma patients alive without disease 11,
      25, and 44 months following initial presentation were recently diagnosed patients
      and, unlike the other patients with KSHV-positive solid lymphomas, received anti
      retroviral therapy. These findings strongly suggest that these decidedly rare
      KSHV-positive solid lymphomas belong to the spectrum of PEL. Therefore, we
      propose that the KSHV-positive solid lymphomas be designated extra-cavitary PELs.

PMID- 15489645
TI  - Pleomorphic hyalinizing angiectatic tumor: analysis of 41 cases supporting
      evolution from a distinctive precursor lesion.
AB  - The pleomorphic hyalinizing angiectatic tumor (PHAT) is a rare, low-grade
      neoplasm that features atypical stromal cells containing hemosiderin, partially
      thrombosed ectatic vessels with circumferential hyalinization, and a variable
      inflammatory infiltrate. Over the years, we have occasionally observed a
      monomorphic partially myxoid spindle cell component (provisionally termed "early
      PHAT") co-existing with classic PHAT. In some instances, this monomorphic lesion
      occurs by itself, suggesting an early stage in the evolution of PHAT. To explore
      this hypothesis and to better define the long-term behavior of PHAT, we have
      reviewed our experience with these lesions. Forty-one cases were identified from
      consultation files. They occurred chiefly in adults (median 51 years, range 10-79
      years) of either sex (23 female, 18 male), ranged from 0.3 to 19.7 cm (median 5.6
      cm), and involved the subcutis of the ankle/foot (N = 15), leg (N = 10), thigh (N
      = 6), and other sites. Thirteen tumors had been present for more than 1 year
      prior to biopsy. Fifteen tumors consisted entirely of typical PHAT. Twelve cases
      conformed to "early PHAT," lacked fully developed features of PHAT, and showed
      instead short fascicles of hemosiderin-stippled spindled cells that infiltrated
      fat and surrounded congeries of small, damaged vessels. With close scrutiny, all
      contained rare pleomorphic cells with intranuclear pseudo-inclusions, as seen in
      typical PHAT. Fourteen cases contained both classic and early PHAT, in variable
      proportions. Follow-up was available in 18 patients (mean 84 months, median 52
      months; range 13-420 months). Six of 18 patients developed recurrences, 1 with
      classic PHAT, 1 with mixed early-classic PHAT, and 4 with early PHAT. Following
      resection, 16 are disease free and 2 have persistent disease. None has developed
      metastasis. Based on the histologic overlap between early and classic PHAT, the
      presence of early PHAT at the periphery of classic PHAT, and the admixture of
      both patterns within the same tumor, we conclude that early PHAT represents a
      precursor lesion for PHAT. It appears essentially identical to the lesion termed
      "hemosiderotic fibrohistiocytic lipomatous lesion," supporting the notion that
      the latter is a neoplastic rather than a reactive lesion. PHAT should be
      considered mesenchymal tumors of intermediate malignancy, given their high rate
      of (sometimes aggressive) local recurrence.

PMID- 15489646
TI  - Cellular angiofibroma: clinicopathologic and immunohistochemical analysis of 51
      cases.
AB  - Cellular angiofibroma is a recently described histologically distinctive benign
      mesenchymal neoplasm composed of 2 principal components, the cellular spindle
      cell component and prominent stromal blood vessels. Cases in males have sometimes
      been called "angiomyofibroblastoma-like tumor." We describe a series of 51 cases
      of cellular angiofibroma to further characterize its clinicopathologic and
      immunohistochemical features. There were 26 women and 25 men, ranging in age from
      22 to 78 years (mean 53.5, median 52 years). Men tended to be older than women.
      Tumor size ranged from 0.6 to 25.0 cm (overall median size 3.9 cm, median in
      women 2.7 cm, median in men 6.7 cm). Most common sites were the vulvovaginal
      region (22 cases) and the inguinoscrotal region (19 cases). Preoperative duration
      (known for 25 patients) ranged from 1 week to 5 years, with presentation as a
      painless mass, except for 1 case each with intermittent genital bleeding and a
      painful mass. Most lesions were located primarily in subcutaneous tissue. Most
      cases were grossly well marginated. Two cases showed foci of hemorrhage and 1
      case showed foci of necrosis. Microscopically, 41 tumors were well circumscribed,
      and 2 tumors infiltrated into the surrounding tissue. All tumors consisted of
      bland, spindle-shaped cells, short bundles of wispy collagen and numerous small-
      to medium-sized thick-walled vessels. Intralesional fat was present in 12 cases
      (6 female and 6 male cases). Mild cytologic atypia (5 cases) and frequent mitoses
      (3 cases) were infrequent; significant nuclear atypia and abnormal mitoses were
      absent. By immunohistochemistry, 29 of 48 tumors (60%) expressed CD34, 10 of 48
      (21%) SMA, 4 of 48 (8%) desmin, but none expressed S-100 protein. Follow-up
      information was available for 40 patients (range 4-168 months; mean 31.2 months)
      and no patient has developed recurrence or metastasis to date.

PMID- 15489647
TI  - Smooth muscle tumors of the ovary: a clinicopathologic study of 54 cases
      emphasizing prognostic criteria, histologic variants, and differential diagnosis.
AB  - We studied 54 ovarian smooth muscle tumors with an emphasis on histologic
      criteria for malignancy. Twenty-two leiomyomas were identified, including 7
      typical, 11 cellular, 2 mitotically active, 1 with bizarre nuclei, and 1 myxoid.
      Follow-up ranging from 12 to 240 months (mean, 77.6 months) was available for 14
      patients; all were alive with no evidence of disease. Of 26 leiomyosarcomas,
      including 2 myxoid leiomyosarcomas, most were readily diagnosed by the presence
      of at least two of the following: moderate or severe cytologic atypia, mitotic
      rate > or =10 mitotic figures per 10 high power fields, and tumor cell necrosis.
      Some cytologically atypical tumors demonstrated lesser mitotic activity of 5 to 9
      mitotic figures per 10 high power fields, in the absence of tumor cell necrosis.
      Sixty percent of these were clinically malignant, supporting a diagnosis of
      leiomyosarcoma in such tumors. Follow-up was available for 21 patients. Seventy
      one percent developed recurrent disease at a mean of 19 months, and 62% died of
      their disease at a mean of 24 months. Four tumors were deemed of uncertain
      malignant potential, and two that were stage II both recurred in the pelvis. One
      case of ovarian intravenous leiomyomatosis had a benign outcome at 42 months, as
      did one case of ovarian leiomyoma with leiomyomatosis peritonealis disseminata at
      180 months. Overall, ovarian smooth muscle tumors encompass the same varied
      histologic spectrum as their uterine counterparts. The main tumors in the
      differential diagnosis are those in the fibroma/thecoma category, spindle cell
      carcinomas, and metastatic gastrointestinal stromal tumors.

PMID- 15489648
TI  - BRAF and KRAS Mutations in hyperplastic polyps and serrated adenomas of the
      colorectum: relationship to histology and CpG island methylation status.
AB  - The aim of this study was to test the hypothesis that mutations of the oncogenes
      BRAF or KRAS are early events in the putative serrated polyp neoplasia pathway
      and more advanced pathology is associated with acquired mutator and suppressor
      gene inactivation by CpG island methylation of promoter regions. We assayed 79
      sporadic hyperplastic polyps (HPs) classified according to the schema of
      Torlakovic et al and 25 serrated adenomas (SAs) for BRAF and KRAS mutations and
      related the findings to histologic characteristics and CpG island methylation
      phenotype (CIMP). Mutations at exon 15, codon 599, of BRAF were assayed using an
      allele-specific PCR (AS-PCR) technique and confirmed in a sample of AS-PCR-
      positive cases by direct sequencing of exon 15. AS-PCR-negative HPs and SAs were
      also sequenced on exon 15 and exon 11 to detect additional mutations. PCR-RFLP
      was used to assay KRAS codon 12 and 13 mutations, and these mutations were
      further validated by direct sequencing of the KRAS gene. BRAF599 mutations were
      identified in a total of 55 HPs (69.6%) and KRAS mutations in a total of 13
      (16.5%). BRAF599 mutations occurred with similar frequencies among microvesicular
      serrated polyp (76.3%) and serrated polyp with abnormal proliferation (82.1%)
      subtypes but less frequently in goblet cell serrated polyps (23.1%). Conversely,
      KRAS mutations were most frequent in goblet cell serrated polyp (46.2%) and less
      frequent in microvesicular serrated polyp (13.2%) and serrated polyp with
      abnormal proliferation (7.1%). BRAF599 and KRAS mutations were present in 15
      (60.0%) and 7 (28.0%) of SAs, respectively. BRAF 599 mutation and KRAS were
      mutually exclusive findings in the polyps studied and one or the other occurred
      in 68 of 79 (86.1%) HPs and 22 of 25 (88.0%) SAs. CpG island methylation
      involving 2 or more genes (CIMP-H) was present in 80.0% of SAs, 75% serrated
      polyp with abnormal proliferations, 47.4% of microvesicular serrated polyps, and
      15.4% of goblet cell serrated polyps. SAs were significantly more likely to be
      CIMP-H than HPs (odds ratio 3.7; 95% confidence interval, 1.27-10.86; P = 0.017).
      A similar high frequency of KRAS or BRAF mutations across the histologic spectrum
      of the serrated polyps assayed suggests that these are early events in the
      serrated polyp neoplasia pathway. In contrast, the association of higher levels
      of CpG island methylation with more advanced histologic changes suggests that CpG
      island methylation plays a role in serrated polyp progression toward colorectal
      carcinoma.

PMID- 15489649
TI  - Villous adenocarcinoma of the colon and rectum: a clinicopathologic study of 36
      cases.
AB  - Some colorectal adenocarcinomas show villous architecture with morphologic
      similarities to tubulovillous or villous adenomas. We reviewed 420 consecutive
      colorectal adenocarcinoma resection specimens and found that 95 tumors (23%)
      showed areas of villous architecture. Thirty-six tumors (8.6%) in 35 patients
      showed more than 50% villous architecture and were designated villous
      adenocarcinomas. Only 42% of the villous adenocarcinomas showed severe atypia and
      only 44% of the available pre-resection biopsies of these tumors were diagnosed
      as adenocarcinoma. Epithelial islands in desmoplastic stroma (EIDS) may be
      helpful in the diagnosis of these tumors. EIDS were found in 97% of the resection
      specimens for villous adenocarcinomas and none of 62 resection specimens for
      tubulovillous or villous adenomas. The presence of EIDS showed a 67% sensitivity,
      100% specificity, and 100% predictive value in the diagnosis of villous
      adenocarcinoma in a blinded review of villous tumors. On review of the pre
      resection biopsies of villous adenocarcinoma without a final diagnosis of
      adenocarcinoma, 40% showed EIDS. Clinical follow-up of the 35 patients with
      villous adenocarcinoma showed that only one died of colorectal adenocarcinoma
      (median follow-up, 46 months). This sole patient dying of colorectal
      adenocarcinoma showed a synchronous advanced stage of nonvillous adenocarcinoma
      at the time of diagnosis. Villous adenocarcinoma is a diagnostically challenging
      subset of colorectal adenocarcinoma, which appears to be associated with a
      favorable prognosis. Classifying these tumors as a special type of colorectal
      cancer may facilitate the development of diagnostic adjuncts and optimal
      treatment protocols.

PMID- 15489650
TI  - Histopathologic aspects of photodynamic therapy for dysplasia and early
      adenocarcinoma arising in Barrett's esophagus.
AB  - The efficacy of photodynamic therapy (PDT) is currently evaluated for the
      treatment of superficial neoplasms arising in Barrett's esophagus (BE). An
      accurate assessment of this technique requires the evaluation of biopsies before
      and after treatment. However, despite the importance of pathology, only a limited
      number of studies have systematically assessed the mucosal changes after PDT. To
      evaluate mucosal changes after PDT, and pathologic variables that may impact on
      the success of this therapy, we analyzed the pre- and post-PDT biopsies of a
      cohort of patients treated by this modality. Thirty-three patients (mean age, 71
      years) with high-grade dysplasia (HGD) and/or intramucosal carcinoma (IMC)
      arising in BE and followed up after PDT using Porfimer sodium form the basis of
      this study. In all patients, a review of all pre- and post-PDT biopsies was
      performed. The variables recorded included the histologic grade and architecture
      of neoplasms, the distribution of neoplasms, and squamous re-epithelialization.
      IMC and HGD coexisted in the pre-PDT biopsies of 18 patients (54.5%). IMC and HGD
      showed a prominent tubular proliferation in 14 patients and displayed a papillary
      pattern (at least partially) in 19 patients. In post-PDT, patches of specialized
      columnar epithelium were buried under squamous epithelium in 17 patients (51.5%),
      and foci of dysplasia/carcinoma covered by squamous epithelium were found in 9
      patients (27.3%). HGD and/or IMC were eradicated in 17 patients (eradicated
      group) and persisted in 16 patients (persistent group). In the persistent group,
      grade and architecture were unchanged after PDT in 62.5% and 87.5% of patients,
      respectively. The persistent group was characterized by: 1) a more frequent
      papillary architecture (P < 0.05), and 2) a diffuse distribution of the neoplasms
      on pre-PDT biopsies (P = 0.05). Singularly, the persistent neoplastic lesions
      were observed in the distal esophagus (P < 0.05). A systematic histopathologic
      evaluation allowed us to draw attention to the fact that distally located and
      papillary-type neoplasia seem resistant to PDT. The higher than expected
      incidence of buried residual neoplastic epithelium should also be emphasized
      since it represents a risk for undetected growth of malignancy.

PMID- 15489651
TI  - Eosinophilic dysplasia of the cervix: a newly recognized variant of cervical
      squamous intraepithelial neoplasia.
AB  - A proportion of cervical squamous intraepithelial lesions encountered in surgical
      pathology practice contain both metaplastic features and some degree of atypia
      [so-called eosinophilic dysplasia (ED)] that defy classification according to
      established criteria. To elucidate the nature of these lesions, we compared 44
      cases of ED to 20 classic high-grade squamous intraepithelial lesions (HSILs) and
      10 squamous metaplasias using a panel of biomarkers and human papillomavirus
      (HPV) testing. EDs were defined as 1) lack of normal maturation; 2) relatively
      abundant eosinophilic cytoplasm and distinct cell borders compared with
      conventional HSIL; 3) mildly to moderately increased nuclear to cytoplasmic
      ratio; and 4) focal dysplastic nuclei showing nuclear enlargement,
      hyperchromasia, variable nuclear membrane irregularities, and appreciable
      nucleoli. Expression of p16 (p16), MIB-1 (Ki-67) labeling index, and HPV DNA
      detection and typing were performed on each case. The majority of EDs showed more
      than three atypical cells in an entire lesion but lack of apparent features of
      HSIL. It was common to find neighboring cervical squamous metaplasia and/or
      conventional SILs (either HSIL or low-grade squamous intraepithelial lesion
      [LSIL]). Among the 44 cases, 18 (45%) ED lesions were found to be associated with
      HSIL, 15 (34%) with LSIL or condylomatous lesions, and 13 (30%) EDs were seen
      without any SILs in the entire specimens. Area of benign squamous metaplasia was
      found in all ED cases. High levels of p16 and MIB-1 expression were seen in 41
      (93%) of 44 ED cases with degrees of immunoreactivity closely resembling those
      seen with HSIL. Of 16 EDs tested, 13 (81%) were positive for HPV DNAs. Among 10
      HPV-positive cases subtyped, 9 (90%) cases contained intermediate- and/or high
      risk HPVs and 1 case contained a novel HPV. In the follow-up of pure ED cases,
      the majority showed presence of dysplastic lesions of either HSIL or LSIL on
      either loop electric excision procedures or Papanicolaou test samples after a 6-
      to 10-week period. Therefore, ED represents an unrecognized and potentially
      clinically significant subgroup of cervical intraepithelial lesions. Based on the
      unique histologic appearance of ED, its association in some cases with HSIL, the
      overall immunohistochemical findings, frequent association of ED with
      intermediate- and/or high-risk HPV infection, and limited follow-up data, we
      believe that ED represents a variant of HSIL (CIN 2). Since ED possesses
      histologic features of both dysplasia and metaplasia, we speculate that it may
      arise from metaplastic cervical squamous epithelium that has subsequently become
      infected with intermediate- or high-risk HPV.

PMID- 15489652
TI  - Immunohistochemical analysis of hSNF5/INI1 distinguishes renal and extra-renal
      malignant rhabdoid tumors from other pediatric soft tissue tumors.
AB  - Malignant rhabdoid tumor (MRT) is a highly aggressive neoplasm that occasionally
      demonstrates phenotypic overlap with other soft tissue malignancies. Molecular
      genetic analysis of MRT frequently demonstrates deletion or mutation of the
      hSNF5/INI1 gene, with corresponding reduced expression at the protein level. INI1
      immunohistochemistry was performed to determine the utility of this method in
      assessing loss of INI1 expression in rhabdoid tumors. Twenty-seven MRTs with
      molecular analysis (19 renal, 8 extra-renal) were evaluated. Seventeen additional
      MRT (10 renal, 7 extra-renal) without INI1 molecular analysis were also analyzed.
      Loss of INI1 expression was observed in the tumor cells in all 44 cases. To
      determine the specificity of this assay, a variety of 45 pediatric soft tissue
      tumors, some of which occasionally display rhabdoid differentiation, were
      investigated. These included Ewing's sarcoma, Wilms' tumor, desmoplastic small
      round cell tumor, clear cell sarcoma, congenital mesoblastic nephroma, synovial
      sarcoma, undifferentiated sarcoma, rhabdomyosarcoma, and epithelioid sarcoma.
      Positive nuclear staining was found in all nonrhabdoid tumors examined. Of
      interest, synovial and epithelioid sarcomas exhibited variable and/or focal
      staining. INI1 antibody immunohistochemistry is useful in confirming the
      histologic diagnosis of renal or extra-renal rhabdoid tumor, especially for cases
      with indeterminate histologic features, equivocal immunophenotypic profiles, or
      uninformative molecular studies.

PMID- 15489653
TI  - Do collision tumors of the gastroesophageal junction exist? A molecular analysis.
AB  - Collision tumors are thought to arise from the accidental meeting of two
      independent tumors. Here we present five gastroesophageal junction tumors
      consisting of two collision tumors and three composite tumors (characterized by
      two divergent lineages originating from the same neoplastic clonal
      proliferation), as diagnosed on histology. In an attempt to prove this
      distinction at a genetic level, we performed TP53 sequence analysis and p53
      immunohistochemistry. In addition, loss of heterozygosity (LOH) analysis using 10
      microsatellite markers was carried out. An identical TP53 mutation and a similar
      pattern of retention and LOH were found in both neoplastic components of the
      presumed collision tumors, suggesting that both components are derived from a
      single precursor cell that undergoes divergent differentiation in the evolution
      of the tumor. In the composite group, 1 case had a genetic basis for the possible
      diagnosis of a collision tumor, with a TP53 mutation in the adenocarcinoma
      component only, and a different pattern of retention and loss of heterozygosity.
      These findings imply that it is not possible to recognize true collision tumors
      from immunohistologic appearance alone and suggest that the long-standing
      histologic criteria for the diagnosis of these neoplasms have no molecular basis.

PMID- 15489654
TI  - The use of cytokeratin 7 and EMA in differentiating ovarian yolk sac tumors from
      endometrioid and clear cell carcinomas.
AB  - Yolk sac tumors (YSTs) have a variety of morphologic patterns, some of which can
      resemble either endometrioid adenocarcinoma (EAC) or clear cell carcinoma (CCC).
      Immunohistochemical staining for alpha-fetoprotein (AFP) is usually only focal
      and thus is not always helpful in the diagnosis of YST, and pancytokeratin (CK)
      is expressed by all three tumors. We studied a battery of immunohistochemical
      markers with specific attention to the utility of cytokeratin 7 (CK7) in
      differentiating YST from EAC and CCC. A total of 46 ovarian tumors were retrieved
      for this study: 16 YST, 19 EAC, and 11 CCC. The three groups were analyzed for
      the expression of CK7, AFP, Leu-M1 (CD15), EMA, and WT1 by immunohistochemistry.
      In addition, CK and c-kit (CD117) were studied in the YSTs. All of the YSTs
      tested (100%) were positive for CK. CK7 was considered negative in all 16 YST
      cases (100%), although a few tumor cells (1%-2%) stained in 4 cases. In contrast,
      17 of 19 EACs and all 11 CCCs had diffuse 3+ to 4+ positivity for CK7; the two
      other EACs showed 2+ positivity for CK7 (40% and 30% of the tumors). AFP was
      positive in 12 of 15 YSTs (80%), but was generally focal with 1+ staining in 10
      cases (67%); only 2 cases were 3+. All of the EACs and CCCs were negative for
      AFP. Leu-M1 was 1+ in 9 of 15 YSTs (60%), while the remaining 6 were considered
      negative. Leu-M1 was positive in 10 of 15 EACs tested (67%), but the staining was
      variable with 1 case 3+, 3 cases 2+, and 6 cases 1+. In the CCCs, 10 cases (91%)
      were 3+ to 4+, and 1 case was 1+. EMA was essentially negative in 15 of 15 YSTs
      (100%), with 3 completely negative and 12 showing very focal (<5%) staining.
      Eight of 12 EACs showed 4+ staining, 3 showed 3+ staining, and 1 showed 2+
      staining. All of the 11 CCCs (100%) showed 4+ staining. WT1 was negative in all
      cases of YST and CCC; 16 of 18 EAC tested (89%) were negative for WT1, but 2
      (11%) were 4+ positive. C-kit was negative in all YSTs. In conclusion, it is
      important for pathologists to be aware that YSTs may mimic EACs and CCCs and that
      this distinction is important for the clinical management of patients with these
      tumors. AFP staining is focal in most YST, so an absence of staining does not
      exclude this diagnosis. CK7 and EMA are essentially negative in YST but are
      diffusely positive in CCC and EAC, making them useful markers for differentiating
      YSTs from both CCCs and EACs. Leu-M1 may also be helpful for distinguishing YSTs
      from CCCs.

PMID- 15489655
TI  - p63 expression in breast cancer: a highly sensitive and specific marker of
      metaplastic carcinoma.
AB  - p63, a member of the p53 gene family, is involved in cellular differentiation and
      is expressed in the nuclei of myoepithelial cells of normal breast ducts and
      lobules. Although p63 has been reported in metaplastic carcinomas of the breast,
      its expression pattern in breast carcinomas and sarcomas has not been fully
      characterized, and its potential diagnostic utility has not been defined. In this
      study, we determined p63 expression in a large number of breast carcinomas,
      including metaplastic carcinomas, and in Phyllodes tumors and sarcomas. We
      examined 189 invasive breast carcinomas, including 15 metaplastic carcinomas, as
      well as 10 Phyllodes tumors, and 5 pure sarcomas of the breast for pattern and
      intensity of p63 staining using an anti-p63 antibody (clone 4A4, Neomarkers). p63
      was strongly expressed in 13 of 15 metaplastic carcinomas (86.7%). p63 was
      positive in all the metaplastic carcinomas with spindle cell and/or squamous
      differentiation (12 of 12), and in 1 of 3 metaplastic carcinomas with cartilage
      foci. In stark contrast, only 1 of 174 (0.6%) nonmetaplastic invasive carcinomas
      was positive for p63. All Phyllodes tumors and sarcomas were consistently
      negative for p63 expression. The sensitivity and specificity of p63 as a
      diagnostic marker for metaplastic carcinoma was 86.7% and 99.4%, respectively. We
      propose the inclusion of p63 as part of the diagnostic workup of challenging
      spindle cell tumors of the breast as a highly specific marker for metaplastic
      carcinomas.

PMID- 15489656
TI  - Penile clear cell carcinoma: a report of 5 cases of a distinct entity.
AB  - We present a series of 5 penile clear cell carcinomas, which arose in middle-aged
      men at the inner side of the foreskin. They were large, exophytic, partly
      ulcerated, and widely invasive tumors with sharp demarcation to the surrounding
      normal skin/mucosa. Histologically, they were composed of large clear cells with
      intracytoplasmic PAS/d-PAS-positive material and showed extensive lymphatic and
      blood vessel invasion. Strong staining with antibodies to Muc-1, EMA, and CEA was
      typical. All carcinomas harbored HPV16 DNA, although only one carcinoma revealed
      HPV-related cytologic cell changes. All 5 patients had extensive, partly cystic
      inguinal lymph node metastases with a striking clear cell differentiation and
      focal dense sclerotic basement membrane material, either at or within several
      months after initial diagnosis. Two patients are alive without disease after 7
      and 10 years. One patient died after 9 months of widespread disease and 2
      patients are presently alive at 7 and 17 months follow-up with widespread
      lymphatic and hematogenous metastases despite adjuvant chemo- and radiation
      therapy. In contrast to squamous cell carcinoma, penile clear cell carcinomas
      show extensive blood and lymph vessel invasion and early metastases to regional
      lymph nodes. Clear cell carcinomas represent a distinct group of penile cancers
      that may have a different clinical behavior than usual penile squamous cell
      carcinomas.

PMID- 15489657
TI  - Cutaneous desmoplastic melanoma: reappraisal of morphologic heterogeneity and
      prognostic factors.
AB  - Desmoplastic melanoma (DM) is a variant of melanoma, which may be confused with
      nonmelanocytic benign or malignant spindle cell proliferations. The histologic
      hallmark of DM is the presence of fusiform melanocytes dispersed in a prominent
      collagenous stroma. Phenotypic heterogeneity of DM is underrecognized.
      Desmoplasia may be prominent throughout the entire tumor ("pure" DM) or represent
      a portion of an otherwise nondesmoplastic melanoma ("combined" DM). We reviewed
      melanomas with desmoplasia from 92 patients seen at a single institution between
      1980 and 2002. Fifty-five of the tumors were pure DM. Thirty-seven were
      classified as combined. Mean follow-up of patients was 46 months for those alive
      at the last follow-up. Univariate analysis of clinical and pathologic parameters
      revealed four significant variables for disease-free survival: Clark level (IV
      vs. V; P = 0.005), DM subtype (pure vs. combined; P = 0.01), tumor mitotic rate
      (<1, 1-4, >4 mitoses/mm; P = 0.01), and tumor thickness (<1 mm, 1-4 mm, >4 mm; P
      = 0.02). Only histologic subtype (P = 0.02) and Clark level (P = 0.05) were
      independently significant by Cox regression analysis. Our results indicate that
      distinguishing pure from combined forms of DM is clinically relevant for
      prognosis (pure forms being associated with longer disease-specific survival).
      Failure to make this distinction may account for conflicting reports in the
      literature on the biologic behavior and prognosis of DM.

PMID- 15489658
TI  - Thymic mucoepidermoid carcinomas: a clinicopathologic study of 10 cases and
      review of the literature.
AB  - BACKGROUND: Primary thymic carcinomas are rare malignant neoplasms, of which at
      least 10 different histologic variants have been described. Among these variants,
      thymic mucoepidermoid carcinomas morphologically similar to the homonymous
      salivary gland counterparts are particularly unusual; only 9 cases for which
      clinicopathologic features were available have been reported. OBJECTIVE: To study
      the clinicopathologic features of primary thymic mucoepidermoid carcinoma in an
      effort to better define their histologic features and biologic behavior. DESIGN:
      The clinical and pathologic features of 10 cases of thymic mucoepidermoid
      carcinoma were reviewed and compared with those of previously reported cases.
      RESULTS: The patients ranged in age from 8 to 84 years (mean 49 years), with 6
      men and 4 women. The initial manifestations included respiratory symptoms and
      weight loss. Some patients were asymptomatic. All tumors were located adjacent to
      residual benign thymic tissue, and 3 cases were associated with multilocular
      thymic cysts. Histologically, the tumors consisted of sheets, lobules and nests
      of squamous, mucinous and intermediate cells in densely fibrotic stroma. There
      were 8 low-grade cases and 2 high-grade cases. The 2 patients with high-grade
      tumors died 1 year after diagnosis, whereas all but 1 patient with low-grade
      tumors in which follow-up was available were found to be alive and well on follow
      up examination. One patient with low-grade tumor but high-stage disease died
      after developing a local recurrence. Among the 9 cases reported in the
      literature, 4 cases resulted in fatal outcomes; 2 cases were high-stage disease
      and 2 were high-grade tumors. CONCLUSIONS: Thymic mucoepidermoid carcinomas are
      predominantly low-grade tumors, and may be associated with multilocular thymic
      cysts. Poor prognosis is related to high-grade histology and high-stage disease.

PMID- 15489659
TI  - The mitosis-specific antibody anti-phosphohistone-H3 (PHH3) facilitates rapid
      reliable grading of meningiomas according to WHO 2000 criteria.
AB  - Mitotic figure (MF) counting is the most objective criterion for grading of
      meningiomas according to the 2000 World Health Organization (WHO) classification.
      However, the search for the area(s) of highest mitotic activity is tedious, and
      there is high interobserver variability in differentiating MF from apoptotic
      cells. We tested the utility of the mitosis-specific marker phosphohistone-H3
      (PHH3) to enhance rapid recognition of MFs and quick reliable grading of
      meningioma. Fifty-four archival meningiomas (26 benign, 20 atypical, 8
      anaplastic) were reclassified according to current WHO criteria. PHH3
      immunostained MFs were counted the same way as in hematoxylin and eosin-stained
      sections. Anti-PHH3-labeled MFs were easily seen and permitted quick
      identification of the area(s) of highest mitotic activity. Count results (mean)
      show a strong correlation between both methods: benign, hematoxylin and eosin
      1.4, PHH3 2.2; atypical, hematoxylin and eosin 9.0, PHH3 15.9; anaplastic,
      hematoxylin and eosin 22.4, PHH3 34.1. PHH3 counting yielded greater sensitivity
      and in 12 cases (22.2%) suggested a change in grade (increased 9; lowered 3). All
      cases in which PHH3 lowered the grade were from older blocks, suggesting a loss
      of antigen preservation. PHH3 immunostaining facilitates the rapid reliable
      grading of meningiomas by focusing attention on the most mitotically active areas
      and by allowing easy and objective differentiation of MFs from apoptotic nuclei.

PMID- 15489660
TI  - Re: Cioc AM, Allen C, Kalmar J, et al. Oral plasmablastic lymphomas in AIDS
      patients are associated with human herpesvirus 8. Am J Surg Pathol. 2004; 25:41
      46.

PMID- 15489661
TI  - Is plasmablastic lymphoma of the oral cavity an HHV-8-associated disease?

PMID- 15489663
TI  - Lung transplantation in a patient with airway-centered fibrosis.

PMID- 15489665
TI  - New guidelines improve treatment of otitis media.

PMID- 15489667
TI  - Personalized prescription pad policies.

PMID- 15489668
TI  - Dysmetabolic syndrome: reducing cardiovascular risk.

PMID- 15489670
TI  - Asthma: helping patients breathe easier.

PMID- 15489672
TI  - Androgen replacement therapy in aging men.

PMID- 15489673
TI  - Care for women choosing medication abortion.

PMID- 15489674
TI  - Are herbal therapies worth the risks?

PMID- 15489823
TI  - Epilepsy: diagnosis and treatment in the 21st century.

PMID- 15489824
TI  - Seizure types, epilepsy syndromes, etiology, and diagnosis.
AB  - The clinical manifestation of epileptic seizures may vary widely from patient to
      patient, depending on the region of the brain involved. Over the centuries, many
      seizure classification systems have been used, and the current most widely used
      classification system is that of the International League Against Epilepsy
      (ILAE). The ILAE system divides seizures into those of partial onset and those of
      generalized onset, depending on whether the initial clinical manifestations
      indicate that one cortical region or both hemispheres are involved at the onset
      of the seizure. Partial seizures are then divided into simple partial seizures,
      in which a fully conscious state is retained, or complex partial seizures, in
      which consciousness is impaired. A more recent classification system based purely
      on symptom features and signs has been proposed, and this system may provide
      advantages for localization, and especially for surgical evaluation. Epilepsy is
      a condition characterized by recurrent unprovoked seizures. Epilepsy may be
      idiopathic, cryptogenic, or symptomatic. Idiopathic epilepsies are generally
      genetic, and while many such syndromes have been described, advances in molecular
      genetics will undoubtedly reveal many more syndromes in the near future.
      Cryptogenic epilepsies are those in which an underlying cause is suspected, but
      the etiology remains undetected. Epilepsies for which there is an underlying
      structural cause or major metabolic derangement are considered symptomatic.
      Common causes and diagnostic evaluation are described in this article.

PMID- 15489825
TI  - Vagus nerve stimulation and Lennox-Gastaut syndrome: a review of the literature
      and data from the VNS patient registry.
AB  - Lennox-Gastaut syndrome (LGS) is a severe form of childhood epilepsy that is
      usually refractory to medical management. When medication fails, alternative
      therapies are considered. Among these are two surgical options: corpus
      callosotomy and vagus nerve stimulation (VNS). Safety and efficacy are two
      important factor to consider when selecting an appropriate treatment. VNS is
      safer than callosotomy, but its efficacy is more difficult to assess. Available
      studies evaluate its effectiveness using a mixed population of patients (some
      with prior epilepsy surgery), a multitude of VNS settings, and variable
      endpoints. To estimate the efficacy of VNS in patients with LGS, a review of the
      medical literature and the VNS Patient Registry was performed. Within the limits
      of this type of study, the results showed that VNS appears to be equally as
      effective as callosotomy. Because VNS has a lower potential for adverse effects,
      these results suggest that VNS should be considered first in appropriately
      selected patients.

PMID- 15489826
TI  - Cognitive difficulties and posttraumatic stress disorder in female victims of
      intimate partner violence.
AB  - Subjective cognitive complaints of women exposed to intimate partner violence
      (IPV) and nonabused women were examined using the Cognitive Difficulties Scale
      (CDS). Cognitive complaints were compared among victims of IPV with a lifetime
      diagnosis of posttraumatic stress disorder (PTSD) (PTSD+; n=20), victims of IPV
      without lifetime PTSD (PTSD-; n=21), and a nonabused comparison group (n=22). The
      results indicated that both the PTSD+ and PTSD- groups had significantly higher
      levels of self-perceived cognitive difficulties than nonabused women.
      Furthermore, PTSD symptom severity was found to be positively correlated with
      self-perceived cognitive difficulties (r=.47). Further research is needed to
      determine whether cognitive complaints are associated with exposure to IPV, with
      the subsequent development of PTSD, or with other not yet understood factors.
      Furthermore, additional work is needed to resolve whether cognitive complaints
      are accompanied by objective evidence of cognitive dysfunction in victims of IPV.

PMID- 15489827
TI  - [First experience of the use of sirolimus covered stents output in the treatment
      of ischemic heart disease].

PMID- 15489828
TI  - [Relationship between psychophysiological personality traits of patients with
      ischemic heart disease, character and severity of coronary vascular bed
      impairement, and biochemical mechanisms of adaptation under conditions of stress
      during surgery].

PMID- 15489829
TI  - [Elevation pressure in morning hours in patients with essential hypertension:
      effect therapy with eprosartan for leading stress tests].

PMID- 15489830
TI  - [Clinical efficacy of noliprel in the treatment of hypertension. Main results of
      ETALON].

PMID- 15489831
TI  - [Novel antithrombotic drugs. From the 19th Congress of the International Society
      on Thrombosis and Haemostasis].

PMID- 15489832
TI  - [Expert consensus document on the use of antiplatelet agents].

PMID- 15489834
TI  - [A polymer-based, paclitaxel-eluting stent in patients with coronary artery
      disease. Results of TAXUS IV].

PMID- 15489835
TI  - [After coronary stenting course of ticlopidine (1 month) compared with that of
      clopidogrel was associated with significantly lower cardiovascular mortality
      during 28 moths follow up].

PMID- 15489836
TI  - [Effects of ranolazine with atenolol, amlodipine, or diltiazem on exercise
      tolerance and angina frequency in patients with severe chronic angina. Results of
      CARISA].

PMID- 15489837
TI  - [Do low risk patients undergoing percutaneous coronary intervention after
      pretreatment with clopidogrel need abciximab infusion? Results of ISAR-REACT
      study].

PMID- 15489838
TI  - [Fibrates: mechanism of action, effect on levels of lipids and risk of coronary
      events. II. Fenofibrate].

PMID- 15489839
TI  - [The use of beta-blockers in patients with hypertension and chronic obstructive
      lung diseases].

PMID- 15489840
TI  - [Ischemic heart disease with low risk of vascular complications -- a novel
      indication for angiotensin converting enzyme inhibitors (results of EUROPA
      trial)].

PMID- 15489841
TI  - [Myocardial infarction in a patient with tetralogy of Fallot].

PMID- 15489842
TI  - [Arterial hypertension and cerebrovascular pathology. Current status of the
      problem].
AB  - In the process of development and progression of arterial hypertension
      hypertensive cerebral angiopathy is formed - that is a complex of intricate
      primarily destructive (acute and recurring) and secondary reparative changes and
      adaptive processes occurring on all structural and functional levels of cerebral
      vascular system. Arterial hypertension in patients with cerebrovascular diseases
      should be treated. Because of heterogeneity of etiology and pathogenetic
      mechanisms of stroke detailed assessment of the state of cerebral vessels, blood
      flow, circulatory and metabolic cerebral reserve is a prerequisite of effective
      and safe antihypertensive therapy, prevention of stroke and other complications.
      This excludes generalized (leveling-off) approach to treatment and prevention of
      various types and subtypes of stroke. A notion that hypertension is a most
      important, independent controllable risk factor of cerebrovascular diseases
      remains definitely valid. However it is far from being a single cause of stroke.

PMID- 15489843
TI  - [Prognostication of coronary atherosclerosis for selection of tactics of
      management of patients with ischemic heart disease].
AB  - AIM: To create an artificial neural network for prognostication of coronary
      atherosclerosis and thus selection of patients requiring invasive interventions.
      METHODS AND RESULTS: Efficacy of prognostication made by a physician and by a
      model was compared basing on probabilistic estimates with consideration of
      individual level of risk. Nineteen clinical and instrumental parameters were
      entered into multifactorial analysis. These parameters included data from
      anamnesis, results of instrumental examination, a priori likelihood of ischemic
      heart disease, and magnitude of individual risk of cardiovascular events. The
      following factors were selected as significant at neural network prognostication
      of coronary atherosclerosis: result of exercise test, typical angina, history of
      myocardial infarction, ECG-signs of left ventricular hypertrophy and a priori
      likelihood of ischemic heart disease. Basing on these data two stage scheme of
      prognostication of coronary atherosclerosis was suggested. CONCLUSION: Thus
      artificial neural network suitable for screening and selection of patients for
      invasive interventions in ambulatory practice was created. Prognosis made with
      the use of artificial neural network was 1.5-3 times more accurate than that made
      by a physician.

PMID- 15489844
TI  - [Clinical efficacy of tianeptine in patients with ischemic heart disease and
      comorbid depression].
AB  - Ischemic heart disease patients (20 men, 20 women, age 36-72 years) with class II
      III effort angina and depression (Beck Depression Inventory -- BDI -- score > or
      = 19) were randomized to standard therapy were treatment of stable ischemic heart
      disease (control group) or standard therapy plus tianeptine 37.5 mg/day. After 6
      weeks 52% decrease of BDI score occurred in tianeptine treated patients (from
      24.9+/-1.2 to 11.9+/-1.5, p<0.001). This was associated with decrease of number
      and severity of cardialgias, better blood pressure control in patients with
      hypertension, lengthening of exercise time during exercise test (by 3.3+/-0.9
      min, p<0.05), and increase of overall index of quality of life (by 2.6+/-0.9
      points, p<0.01). No dynamics of these parameters occurred in control group.

PMID- 15489845
TI  - [Single-photon emission computed tomography in diagnosis of left ventricular post
      infarction aneurysm].
AB  - AIM: To assess value of single-photon emission computed tomography with (99m)Tc
      sestamibi ((99m)Tc MIBI SPECT) for detection of post-infarction left ventricular
      aneurysm in patients with coronary artery disease. MATERIAL: Fifty nine patients
      were operated upon because of coronary heart disease. In 27 patients with post
      infarction left ventricular aneurysm modified Dor operation (aneurysmectomy with
      endoventricular circular patch plasty reconstruction) was performed. In 24
      patients with extended cardiosclerosis direct myocardial revascularization was
      conducted. RESULTS AND CONCLUSION: Comparison of (99m)Tc MIBI SPECT data obtained
      at rest and during dobutamine stress test revealed some diagnostic features
      characteristic of patients with left ventricular post-infarction aneurysm.
      Quantitative and qualitative assessment of viability of myocardium in basal and
      "borderline" zones influenced not only the volume of revascularization, it was
      important for preliminary determination of post-infarction left ventricular
      aneurysm resection level, selection of type of plasty, prognostication of
      complications in immediate and remote postoperative periods.

PMID- 15489846
TI  - [Simple cardiovascular reflex test during hospitalization due to myocardial
      infarction predicts sudden but not non-sudden cardiac death during 2 years follow
      up].
AB  - Prognostic significance of heart rate (HR) response to easy to perform
      provocative maneuvers such as Valsalva maneuver and deep breath requires further
      elucidation. METHODS: Valsalva maneuver with calculation of Valsalva ratio (VR)
      and deep breath test with calculation of difference between average maximal and
      minimal HR during first minute of test (HRD) were performed in 210 patients on
      days 4-11 of myocardial infarction (MI). This analysis included data from 188
      patients (68,1% men, age 34-75 years, 93.6% on beta-blockers during test).
      RESULTS: During period of follow up for 2.1+/-0.8 years there were 9 sudden (SD)
      and 13 non-sudden (non-SD) cardiac deaths. ROC-analysis allowed to determine
      optimal prognostic values of VR (<1.13) and HRD (<3.36) for SD. For non-SD these
      values could not be determined. According to univariate logistic regression
      analysis predictors of SD were as follows: VR<1.13 (OR 7.8, 95% CI 1.6-39.0,
      p=0.012), HRD <3.36 (OR 4.3, 95%CI 1.1-16.9, p=0.034), history of MI, ventricular
      fibrillation during first 24 h of MI, clinical heart failure (NYHA class II-III)
      on the day of tests. At multivariate analysis independent predictors of SD were
      history of MI (OR 8.3, 95% CI 1.5-46.2, p=0.015), ventricular fibrillation during
      first 24 h of MI (OR 72.3, 95% CI 5.1-1032.9, p=0.002) and VR <1.13 (OR 7.36, 95%
      CI 1.3-41.7, p=0.024). Univariate predictors of non-SD included history of MI,
      history of heart failure, HR on admission and postinfarction angina. HR on
      admission >/= 91 bpm was the single independent predictor of non-SD (OR 3.8, 95%
      CI 1.1-13.0, p=0.034). CONCLUSION: Valsalva ratio <1.13 on days 4-11 of MI in
      patients with sinus rhythm and without severe heart failure was associated with
      high risk of SD but not of non-SD during 2 years of follow up.

PMID- 15489847
TI  - [Efficacy and tolerability of felodipine based antihypertensive therapy in
      hospitalized patients with hypertension].
AB  - AIM: To compare efficacy and tolerability of felodipine based antihypertensive
      therapy with those of standard hospital treatment of hypertension. MATERIAL:
      Inhospital patients were randomized 1:2 to standard antihypertensive therapy or
      to therapy which included felodipine (n=50 and 100, 36 and 35% men, mean age
      66.0+/-8.4 and 64.3+/-8.1 years, initial blood pressure 162.4+/-9.3/99.3+/-6.4
      and 163.2+/-10.3/98.2+/-6.5 mm Hg, respectively). Felodipine was used: (1) as
      first drug with subsequent addition of other drugs as required; (2) after
      cessation of previously ineffective therapy; (3) in cases of intolerance to
      previous therapy, (4) as supplementation to previously insufficiently effective
      therapy. Results. At discharge in felodipine group 6, 25, 29 and 40% of patients
      received mono- (felodipine 10 mg/day), 2, 3 and 4 component therapy,
      respectively. In standard treatment group all patients received combination
      therapy with 3 (48%) or 4 (52%) drugs. Felodipine group compared with group of
      standard therapy was characterized by less frequent correction of
      antihypertensive therapy (0.8+/-0.6 and 2.2+/-0.9, p<0.05), smaller number of
      drugs used (3.03+/-0.95 and 3.52+/-0.5, p<0.01), more frequently achievement of
      target blood pressure level (88 and 64%, p=0.0075), less pronounced difference
      between morning and evening self-measured blood pressure. CONCLUSION: The use of
      felodipine in hospitalized patients with hypertension allowed achieving target
      blood pressure with fewer drugs. Felodipine was safe and well tolerated.

PMID- 15489848
TI  - [Levels of sex hormones in obese women with hypertension during various periods
      of reproductive activity].
AB  - AIM: To assess effects of hypertension and obesity on blood plasma levels of sex
      hormones and gonadotropins in fertile and postmenopausal women. MATERIAL: We
      assessed endocrinological status and measured levels of sex hormones and
      gonadotropins in 228 women with grade I-III hypertension (WHO, 1999) and 114
      normotensive women of fertile and postmenopausal ages (17 to 74 years). There was
      a definite relationship between obesity and levels of sex hormones which did not
      depend on blood pressure level. The authors regarded this relationship as an
      endocrinological consequence of obesity. Severity of hypertension was associated
      with elevation of luteinizing and follicle-stimulating hormones and lowering of
      progesterone level in fertile women and with elevated levels of sex hormones in
      blood plasma in menopausal women. The authors interpreted the latter phenomenon
      as a sign of adrenal gland hyperfunction.

PMID- 15489849
TI  - [Decreased ATP-synthesis ability of brain mitochondria in spontaneously
      hypertensive rats].
AB  - It has been shown previously that a decrease of ATP amount and changed balance of
      other macroergic phosphates occurs in different tissues of spontaneously
      hypertensive rats (SHR) compared with control normotensive rats (WKY). AIM: To
      assess the ability of SHR brain isolated mitochondria to synthesize ATP and to
      elucidate its relation to extramitochondrial calcium concentration. RESULTS: The
      present work shows for the first time that SHR brain mitochondria initially
      differ from WKY ones by decreased (by 30%) ATP synthesis rate. When calcium
      concentration is increased up to 20 or 40 micromole/l ATP synthesis rates in WKY
      and SHR mitochondria are about one half compared with the condition when the
      medium does not contain calcium, but the differences between SHR and WKY remain
      the same. CONCLUSION: Decreased ATP synthesis rate in SHR mitochondria may be
      considered as the main cause of cell energy deficiency observed in experimental
      variant of primary arterial hypertension.

PMID- 15489850
TI  - [Stroke and other tromboembolic complications in atrial fibrillation. Part I.
      Prevalence and risk factors].
AB  - In a series of papers the authors discuss problems of epidemiology and drug
      prevention of stroke and other thromboembolic complications in patients with
      atrial fibrillation. Part I contains data on frequency of strokes in different
      categories of patients as well as review of main risk factors and mechanisms of
      development of stroke and other systemic embolic complications in various types
      of atrial fibrillation. Application of transthoracic and transesophageal
      echocardiography for assessment of risk of stroke and other systemic emboli is
      also discussed.

PMID- 15489851
TI  - [The role of insulin resistance in diagnosis of metabolic syndrome].
AB  - Early diagnosis of metabolic syndrome is based on detection of insulin
      resistance, hyperinsulinemia, and clinical presentations of this syndrome.
      Differences in approaches to diagnosis of metabolic syndrome and its multi
      component nature hamper comparison of results of different studies and
      elaboration of generalized guidelines for selection of high risk groups and
      prevention of cardiovascular diseases and type 2 diabetes. Until present there
      are no common criteria of the syndrome and this makes difficult standardization
      of methodology of its investigation. Several organizations (WHO, National
      Cholesterol Education Program, European Group for the Study of Insulin
      Resistance) issued documents in which diagnostic approaches to detection of
      metabolic syndrome and its separate components have been formulated. These
      approaches as well as comparative analysis of direct and calculated methods of
      assessment of insulin resistance are presented in this review.

PMID- 15489852
TI  - Two anterograde intraflagellar transport motors cooperate to build sensory cilia
      on C. elegans neurons.
AB  - Cilia have diverse roles in motility and sensory reception and their dysfunction
      contributes to cilia-related diseases. Assembly and maintenance of cilia depends
      on the intraflagellar transport (IFT) of axoneme, membrane, matrix and signalling
      proteins to appropriate destinations within the organelle. In the current model,
      these diverse cargo proteins bind to multiple sites on macromolecular IFT
      particles, which are moved by a single anterograde IFT motor, kinesin-II, from
      the ciliary base to its distal tip, where cargo-unloading occurs. Here, we
      describe the observation of fluorescent IFT motors and IFT particles moving along
      distinct domains within sensory cilia of wild-type and IFT-motor-mutant
      Caenorhabditis elegans. We show that two anterograde IFT motor holoenzymes,
      kinesin-II and Osm-3-kinesin, cooperate in a surprising way to control two
      pathways of IFT that build distinct parts of cilia. Instead of each motor
      independently moving its own specific cargo to a distinct destination, the two
      motors function redundantly to transport IFT particles along doublet microtubules
      adjacent to the transition zone to form the axoneme middle segment. Next, Osm-3
      kinesin alone transports IFT particles along the distal singlet microtubules to
      stabilize the distal segment. Thus, the subtle coordinate activity of these IFT
      motors creates two sequential transport pathways.

PMID- 15489853
TI  - Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic
      right ventricular cardiomyopathy.
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with
      fibrofatty replacement of cardiac myocytes, ventricular tachyarrhythmias and
      sudden cardiac death. In 32 of 120 unrelated individuals with ARVC, we identified
      heterozygous mutations in PKP2, which encodes plakophilin-2, an essential
      armadillo-repeat protein of the cardiac desmosome. In two kindreds with ARVC,
      disease was incompletely penetrant in most carriers of PKP2 mutations.

PMID- 15489854
TI  - Loss-of-function mutations in LEMD3 result in osteopoikilosis, Buschke-Ollendorff
      syndrome and melorheostosis.
AB  - Osteopoikilosis, Buschke-Ollendorff syndrome (BOS) and melorheostosis are
      disorders characterized by increased bone density. The occurrence of one or more
      of these phenotypes in the same individual or family suggests that these entities
      might be allelic. We collected data from three families in which affected
      individuals had osteopoikilosis with or without manifestations of BOS or
      melorheostosis. A genome-wide linkage analysis in these families, followed by the
      identification of a microdeletion in an unrelated individual with these diseases,
      allowed us to map the gene that is mutated in osteopoikilosis. All the affected
      individuals that we investigated were heterozygous with respect to a loss-of
      function mutation in LEMD3 (also called MAN1), which encodes an inner nuclear
      membrane protein. A somatic mutation in the second allele of LEMD3 could not be
      identified in fibroblasts from affected skin of an individual with BOS and an
      individual with melorheostosis. XMAN1, the Xenopus laevis ortholog, antagonizes
      BMP signaling during embryogenesis. In this study, LEMD3 interacted with BMP and
      activin-TGFbeta receptor-activated Smads and antagonized both signaling pathways
      in human cells.

PMID- 15489855
TI  - Genetic dissection of a behavioral quantitative trait locus shows that Rgs2
      modulates anxiety in mice.
AB  - Here we present a strategy to determine the genetic basis of variance in complex
      phenotypes that arise from natural, as opposed to induced, genetic variation in
      mice. We show that a commercially available strain of outbred mice, MF1, can be
      treated as an ultrafine mosaic of standard inbred strains and accordingly used to
      dissect a known quantitative trait locus influencing anxiety. We also show that
      this locus can be subdivided into three regions, one of which contains Rgs2,
      which encodes a regulator of G protein signaling. We then use quantitative
      complementation to show that Rgs2 is a quantitative trait gene. This combined
      genetic and functional approach should be applicable to the analysis of any
      quantitative trait.

PMID- 15489856
TI  - Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cag
      pathogenicity island.
AB  - Epithelial cells can respond to conserved bacterial products that are
      internalized after either bacterial invasion or liposome treatment of cells. We
      report here that the noninvasive Gram-negative pathogen Helicobacter pylori was
      recognized by epithelial cells via Nod1, an intracellular pathogen-recognition
      molecule with specificity for Gram-negative peptidoglycan. Nod1 detection of H.
      pylori depended on the delivery of peptidoglycan to host cells by a bacterial
      type IV secretion system, encoded by the H. pylori cag pathogenicity island.
      Consistent with involvement of Nod1 in host defense, Nod1-deficient mice were
      more susceptible to infection by cag pathogenicity island-positive H. pylori than
      were wild-type mice. We propose that sensing of H. pylori by Nod1 represents a
      model for host recognition of noninvasive pathogens.

PMID- 15489857
TI  - Identification of an AID-independent pathway for chromosomal translocations
      between the Igh switch region and Myc.
AB  - Chromosomal translocations involving immunoglobulin heavy chain (Igh) switch
      regions and an oncogene such as Myc represent initiating events in the
      development of many B cell malignancies. These translocations are widely thought
      to result from aberrant class-switch recombination. To test this model, we
      measured translocations in mice deficient in activation-induced cytidine
      deaminase (AID) that lack class-switch recombination. We found that AID made no
      measurable contribution to the generation of initial translocations, indicating
      that the intrinsic fragility of the switch regions or a pathway unrelated to AID
      is responsible for these translocations. In contrast, the outgrowth of
      translocation-positive cells was dependent on AID, raising the possibility that
      AID is important in tumor progression, perhaps by virtue of its mutagenic
      properties.

PMID- 15489858
TI  - Heparin prevents antiphospholipid antibody-induced fetal loss by inhibiting
      complement activation.
AB  - The antiphospholipid syndrome (APS) is defined by thrombosis and recurrent
      pregnancy loss in the presence of antiphospholipid (aPL) antibodies and is
      generally treated with anticoagulation therapy. Because complement activation is
      essential and causative in aPL antibody-induced fetal injury, we hypothesized
      that heparin protects pregnant APS patients from complications through inhibition
      of complement. Treatment with heparin (unfractionated or low molecular weight)
      prevented complement activation in vivo and in vitro and protected mice from
      pregnancy complications induced by aPL antibodies. Neither fondaparinux nor
      hirudin, other anticoagulants, inhibited the generation of complement split
      products or prevented pregnancy loss, demonstrating that anticoagulation therapy
      is insufficient protection against APS-associated miscarriage. Our data indicate
      that heparins prevent obstetrical complications in women with APS because they
      block activation of complement induced by aPL antibodies targeted to decidual
      tissues, rather than by their anticoagulant effects.

PMID- 15489859
TI  - S-Glutathiolation by peroxynitrite activates SERCA during arterial relaxation by
      nitric oxide.
AB  - Nitric oxide (NO) physiologically stimulates the sarco/endoplasmic reticulum
      calcium (Ca(2+)) ATPase (SERCA) to decrease intracellular Ca(2+) concentration
      and relax cardiac, skeletal and vascular smooth muscle. Here, we show that NO
      derived peroxynitrite (ONOO(-)) directly increases SERCA activity by S
      glutathiolation and that this modification of SERCA is blocked by irreversible
      oxidation of the relevant cysteine thiols during atherosclerosis. Purified SERCA
      was S-glutathiolated by ONOO(-) and the increase in Ca(2+)-uptake activity of
      SERCA reconstituted in phospholipid vesicles required the presence of
      glutathione. Mutation of the SERCA-reactive Cys674 to serine abolished these
      effects. Because superoxide scavengers decreased S-glutathiolation of SERCA and
      arterial relaxation by NO, ONOO(-) is implicated as the intracellular mediator.
      NO-dependent relaxation as well as S-glutathiolation and activation of SERCA were
      decreased by atherosclerosis and Cys674 was found to be oxidized to sulfonic
      acid. Thus, irreversible oxidation of key thiol(s) in disease impairs NO-induced
      relaxation by preventing reversible S-glutathiolation and activation of SERCA by
      NO/ONOO(-).

PMID- 15489860
TI  - Enhanced insulin sensitivity, energy expenditure and thermogenesis in adipose
      specific Pten suppression in mice.
AB  - Pten is an important phosphatase, suppressing the phosphatidylinositol-3
      kinase/Akt pathway. Here, we generated adipose-specific Pten-deficient (AdipoPten
      KO) mice, using newly generated Acdc promoter-driven Cre transgenic mice.
      AdipoPten-KO mice showed lower body and adipose tissue weights despite
      hyperphagia and enhanced insulin sensitivity with induced phosphorylation of Akt
      in adipose tissue. AdipoPten-KO mice also showed marked hyperthermia and
      increased energy expenditure with induced mitochondriagenesis in adipose tissue,
      associated with marked reduction of p53, inactivation of Rb, phosphorylation of
      cyclic AMP response element binding protein (CREB) and increased expression of
      Ppargc1a, the gene that encodes peroxisome proliferative activated receptor gamma
      coactivator 1 alpha. Physiologically, adipose Pten mRNA decreased with exposure
      to cold and increased with obesity, which were linked to the mRNA alterations of
      mitochondriagenesis. Our results suggest that altered expression of adipose Pten
      could regulate insulin sensitivity and energy expenditure. Suppression of adipose
      Pten may become a beneficial strategy to treat type 2 diabetes and obesity.

PMID- 15489861
TI  - Shape-selective RNA recognition by cysteinyl-tRNA synthetase.
AB  - The crystal structure of Escherichia coli cysteinyl-tRNA synthetase (CysRS) bound
      to tRNA(Cys) at a resolution of 2.3 A reveals base-specific and shape-selective
      interactions across an extensive protein-RNA recognition interface. The complex
      contains a mixed alpha/beta C-terminal domain, which is disordered in the
      unliganded enzyme. This domain makes specific hydrogen bonding interactions with
      all three bases of the GCA anticodon. The tRNA anticodon stem is bent sharply
      toward the enzyme as compared with its conformation when bound to elongation
      factor Tu, providing an essential basis for shape-selective recognition. The
      CysRS structure also reveals interactions of conserved enzyme groups with the
      sugar-phosphate backbone in the D loop, adjacent to an unusual G15.G48 tertiary
      base pair previously implicated in tRNA aminoacylation. A combined mutational
      analysis of enzyme and tRNA groups at G15.G48 supports the notion that contacts
      between CysRS and the sugar-phosphate backbone contribute to recognition by
      indirect readout.

PMID- 15489862
TI  - Regulated interactions of mtHsp70 with Tim44 at the translocon in the
      mitochondrial inner membrane.
AB  - Preproteins synthesized on cytosolic ribosomes, but destined for the
      mitochondrial matrix, pass through the presequence translocase of the inner
      membrane. Translocation is driven by the import motor, having at its core the
      essential chaperone mtHsp70 (Ssc1 in yeast). MtHsp70 is tethered to the
      translocon channel at the matrix side of the inner membrane by the peripheral
      membrane protein Tim44. A key question in mitochondrial import is how the mtHsp70
      Tim44 interaction is regulated. Here we report that Tim44 interacts with both the
      ATPase and peptide-binding domains of mtHsp70. Disruption of these interactions
      upon binding of polypeptide substrates requires concerted conformational changes
      involving both domains of mtHsp70. Our results fit a model in which regulated
      interactions between Tim44 and mtHsp70, controlled by polypeptide binding, are
      required for efficient translocation across the mitochondrial inner membrane in
      vivo.

PMID- 15489863
TI  - Sequential reduced- and full-intensity allografting using same donor in a child
      with chronic granulomatous disease and coexistent, significant comorbidity.

PMID- 15489864
TI  - Fatal West Nile virus encephalitis following autologous peripheral blood stem
      cell transplantation.

PMID- 15489865
TI  - Lenograstim after autologous peripheral blood progenitor cell transplantation:
      results of a double-blind, randomized trial.
AB  - A phase III, randomized, double-blind, placebo-controlled, multi-center trial was
      conducted in order to compare the incidence of microbiologically defined
      infections occurring after high-dose chemotherapy (HDT) and ASCT in 98 patients
      given lenograstim (Granocyte) and 94 patients given placebo after
      transplantation. Hematopoietic recovery, the use of i.v. antibiotics, the numbers
      of red blood cell and platelet transfusions, the days spent in hospital, and the
      days on parenteral nutrition were also compared. The incidence of infections
      until neutrophil recovery was significantly less in patients who received
      lenograstim after HDT and ASCT as compared to patients who received placebo (66
      of 98 vs 86 of 94 patients, P<0.001). Lenograstim also significantly reduced the
      use of i.v. antibiotics (P<0.001) and the median duration of i.v. antibiotic
      treatment (8 days vs 10 days, P=0.04), improved neutrophil recovery (absolute
      neutrophil count >0.5 x 10(9)/l: 11 days vs 15 days, P<0.001) and reduced the
      number of days spent in hospital (15 days vs 17 days, P<0.001). The
      administration of lenograstim after HDT and ASCT significantly reduces the
      incidence of microbiologically defined infections until neutrophil recovery. It
      also leads to less use of antibiotics and earlier discharge from hospital.

PMID- 15489866
TI  - Fludarabine, cyclophosphamide plus thymoglobulin conditioning regimen for
      unrelated bone marrow transplantation in severe aplastic anemia.
AB  - Antithymocyte globulin (ATG) has been used in severe aplastic anemia (SAA) as a
      part of the conditioning regimen. Among the many kinds of ATG preparations,
      thymoglobulin had been found to be more effective in preventing GVHD and
      rejection of organ transplants. As the fludarabine-based conditioning regimens
      without total body irradiation have been reported to be promising for bone marrow
      transplantation (BMT) from alternative donors in SAA, thymoglobulin was added to
      fludarabine and cyclophosphamide conditioning to reduce GVHD and to allow good
      engraftment in unrelated BMT. Five patients underwent BMT with cyclophosphamide
      (50 mg/kg once daily i.v. on days -9, -8, -7 and -6), fludarabine (30 mg/m2 once
      daily i.v. on days -5, -4, -3 and -2) and thymoglobulin (2.5 mg/kg once daily
      i.v. on days -3, -2 and -1) from HLA-matched unrelated donors. Complete donor
      type hematologic recovery was achieved in all patients. No serious complication
      occurred during BMT. Only one patient developed grade I acute GVHD resolved
      spontaneously. Except for one who had rupture of hepatic adenoma 78 days after
      BMT, all the other four patients are still alive with median 566 days.
      Fludarabine, cyclophosphamide plus thymoglobulin conditioning allows for the
      promising results of good engraftment, tolerable toxicity and minimal GVHD.

PMID- 15489867
TI  - Hematopoietic stem cell transplantation in severe congenital neutropenia:
      experience of the French SCN register.
AB  - Our objective was to study the outcome of allogeneic hematopoietic stem cell
      transplantation (HSCT) in patients with severe congenital neutropenia (SCN).
      Among 101 cases of SCN included in the French Severe Chronic Neutropenia
      Registry, nine patients received HSCT between 1993 and 2003, in seven
      institutions. The indications were nonresponse to G-CSF therapy in four cases,
      bone marrow failure in one case, and myelodysplastic syndrome or leukemia in four
      cases. The conditioning regimen consisted of total body irradiation in two cases
      and chemotherapy alone in the other seven cases. Seven patients received stem
      cells from unrelated donors and two from identical siblings. Engraftment occurred
      in all but one of the patients. Three patients died. The respective causes of
      death were graft-versus-host disease, infection, and EBV post-transplant
      lymphoproliferative disease. Six patients are alive and in complete remission,
      with a median follow-up of 3.1 years. These results indicate that HSCT is
      feasible for patients with SCN who do not respond to G-CSF, who have malignant
      transformation, or who are at a high risk of malignant transformation, even if an
      HLA-identical sibling donor is not available.

PMID- 15489868
TI  - Genomic screening and complications of hematopoietic stem cell transplantation:
      has the time come?
AB  - The occurrence of toxic complications following hematopoietic stem cell
      transplantation (HSCT) is highly variable and dependent on a multitude of host,
      donor, and treatment factors. The increasingly broad indications for HSCT and the
      need to provide this treatment option to older and/or more debilitated patients
      emphasizes the importance of refining our methods of predicting and ameliorating
      these toxicities. Late complications (occurring after day 100) also pose a threat
      to quality of life after HSCT. Genetic polymorphisms in key molecular pathways in
      the host are likely to contribute significantly to the observed variability in
      the development HSCT-associated complications. Hepatic veno-occlusive disease and
      acute lung injury, two of the most serious organ toxicities that occur, represent
      useful paradigms for the identification of genetic polymorphisms in enzyme
      systems that modulate local and systemic responses to oxidant stress during
      transplant conditioning therapy. Ongoing studies in this area are providing clues
      to the prevention of adverse clinical outcomes based on the genetic milieu. This
      review of studies in HSCT that explore genetic risk factors for transplant
      complications indicates that significant progress is being made in this rapidly
      evolving area. However, further large-scale clinical and translational studies
      are needed before genomic screening can be widely used to individualize
      treatment.

PMID- 15489869
TI  - Granisetron vs ondansetron for prevention of nausea and vomiting in hematopoietic
      stem cell transplant patients: results of a prospective, double-blind, randomized
      trial.
AB  - The serotonin type-3 (5-HT3) antagonists represent a significant advance in the
      prevention of acute nausea and vomiting (N/V) from highly emetogenic
      chemotherapy. We sought to determine if any differences in efficacy or adverse
      effects exist between two such agents, ondansetron and granisetron, during
      conditioning therapy for hematopoietic stem cell transplantation (HSCT). Patients
      were randomized to receive either ondansetron 0.15 mg/kg intravenously every 8 h
      or granisetron 10 microg/kg intravenously daily. Additionally, all patients
      received scheduled dexamethasone and lorazepam. Prophylaxis was continued until
      24 h after completion of chemotherapy. Nausea and distress were measured
      subjectively with visual analog scales and emetic episodes were quantified. Of
      the 110 randomized patients, 96 were evaluable for efficacy and safety. No
      significant differences in efficacy were observed between the ondansetron- and
      granisetron-treated patients, evaluated by comparing the degree of nausea and
      distress, number of emetic episodes and overall control of emesis. The adverse
      effects were also comparable and no patients were removed from study because of
      severe toxicities. This trial demonstrates that ondansetron and granisetron are
      equally effective at preventing acute N/V associated with conditioning therapy
      frequently used for HSCT. The agent of choice should be based on drug acquisition
      cost or preference.

PMID- 15489870
TI  - CD34+ cell dose, conditioning regimen and prior chemotherapy: factors with
      significant impact on the early kinetics of donor chimerism after allogeneic
      hematopoietic cell transplantation.
AB  - The aim of this study was to define factors that significantly influence the
      early kinetics of donor chimerism after transplantation. In a retrospective
      study, the percentage of donor chimerism in peripheral blood measured with sex
      chromosome-specific probes and fluorescence-in situ hybridization was analyzed in
      184 recipients of allogeneic hematopoietic cells between days 1 and 30. Using a
      generalized linear model for longitudinal observations, the dose of CD34+ cells
      infused had a significant impact on the slope of donor chimerism. In multivariate
      analysis, cell doses of 2-8 x 10(6)/kg (P=0.001) and <2 x 10(6) CD34+ cells/kg
      (P<0.0001) were associated with slower increase of donor chimerism compared to
      >8.0 x 10(6) CD34+ cells/kg. In addition, fludarabine-based reduced-intensity
      conditioning resulted in a significant delay of donor cell increase compared to
      standard conditioning therapy (P=0.0001). The application of chemotherapy before
      the start of conditioning (P=0.0003) and the use of antithymocyte globulin
      (P=0.003) were associated with a faster increase of donor chimerism. The factors
      identified in this study can be used to predict the kinetics of early donor
      chimerism for an individual patient.

PMID- 15489871
TI  - Recurrent nephrotic syndrome associated with graft-versus-host disease.

PMID- 15489872
TI  - Use of leflunomide in an allogeneic bone marrow transplant recipient with
      refractory cytomegalovirus infection.
AB  - Ganciclovir-resistant cytomegalovirus (CMV) infection is an emerging problem in
      transplant recipients. Foscarnet resistance and cidofovir resistance have also
      been described, but no previous reports have suggested treatment regimens for
      patients with CMV refractory to all three of these drugs. Leflunomide, an
      immunosuppressive drug used in rheumatoid arthritis and in rejection in solid
      organ transplantation, has been reported to have novel anti-CMV activity.
      However, its clinical utility in CMV treatment has not been described previously.
      We report an allogeneic bone marrow transplant recipient who developed CMV
      infection refractory to sequential therapy with ganciclovir, foscarnet, and
      cidofovir. The patient was ultimately treated with a combination of leflunomide
      and foscarnet. Both phenotypic and genotypic virologic analysis was performed on
      sequential CMV isolates. The patient's high CMV-DNA viral load became
      undetectable on leflunomide and foscarnet, but the patient, who had severe graft
      versus-host disease (GVHD) of the liver, expired with progressive liver failure
      and other complications. We concluded that leflunomide is a new immunosuppressive
      agent with anti-CMV activity, which may be useful in the treatment of
      multiresistant CMV. However, the toxicity profile of leflunomide in patients with
      underlying GVHD remains to be defined.

PMID- 15489873
TI  - Partial CD8+ T-cell depletion of allogeneic peripheral blood stem cell
      transplantation is insufficient to prevent graft-versus-host disease.
AB  - Prior studies suggest that depletion of CD8+ T cells from donor bone marrow or
      donor lymphocyte infusions can reduce graft-versus-host disease (GVHD) without
      compromising graft-versus-leukemia. We explored CD8 depletion in patients
      undergoing matched related donor (MRD, n=25) and unrelated donor (URD, n=16)
      peripheral blood stem cell transplantation following myeloablative conditioning
      with cyclophosphamide (60 mg/kg/day i.v. x 2) and total body irradiation (200 cGy
      x 7 fractions). Ex vivo incubation of mobilized donor peripheral blood cells with
      anti-CD8 antibody coated high-density microparticles removed 99% of CD8+ cells.
      The median number of CD8+ cells infused was 3.9 x 10(5) cells/kg (2.2 x 10(5) in
      MRD, and 8.1 x 10(5) in URD patients). Post transplant immune suppression
      included tacrolimus in the MRD cohort, and tacrolimus plus mini-methotrexate (5
      mg/m2 days +1, 3, 6, 11) in the URD cohort. All 41 patients engrafted. Grade 2-4
      acute GVHD incidence was 61% (44% MRD, 88% URD). Chronic GVHD incidence was 50%
      (48% MRD, 55% URD). Relapse incidence was 4.9%. Estimated event-free and overall
      survival rates were 65 and 63%, respectively, at 1 year and 56 and 57%,
      respectively, at 2 years. There was no correlation between CD8+ number and GVHD
      or survival. A 2-log depletion of CD8+ cells from PBSC is insufficient to prevent
      GVHD.

PMID- 15489874
TI  - Successful pregnancies after bone marrow transplantation for Fanconi anemia.

PMID- 15489875
TI  - High-dose immune suppression and autologous hematopoietic stem cell
      transplantation in refractory pemphigus foliaceus.

PMID- 15489876
TI  - Long-term immunity to poliovirus after vaccination of allogeneic stem cell
      transplant recipients.
AB  - Revaccination with poliovirus after allogeneic stem cell transplant (SCT) is
      usually effective, but the longevity of this immunity is unknown. Therefore,
      poliovirus immunity was studied in 134 patients having survived at least 5 years
      after vaccination. The median follow-up from vaccination was 8 years (1-19
      years). In all, 21 (15.6%) patients had become seronegative to at least one of
      the poliovirus serotypes during follow-up. The estimated probabilities of
      remaining immune to poliovirus at 5 and 10 years after vaccination were 94 and
      94% for subtype 1, 98 and 94% for subtype 2, and 93 and 90% for subtype 3,
      respectively. In multivariate analysis, the only risk factor for loss of immunity
      was younger patient age (P < 0.01), and there was a strong trend for patients
      with chronic GVHD to lose immunity more rapidly (P = 0.07). A total of 14
      patients received a booster dose of an inactivated poliovirus vaccine and all
      responded. We conclude that poliovirus immunity is retained long term after
      revaccination in most patients after allogeneic SCT.

PMID- 15489877
TI  - Ex vivo expansion of megakaryocyte precursor cells in autologous stem cell
      transplantation for relapsed malignant lymphoma.
AB  - To evaluate the impact of ex vivo expanded megakaryocyte (MK) progenitors on high
      dose chemotherapy-induced thrombocytopenia, we conducted a phase II study in 10
      patients with relapsed lymphoma. Two fractions of peripheral blood progenitor
      cells (PBPC) were cryopreserved, one with enough cells for at least 2 x 10(6)
      CD34+ cells/kg and a second obtained after CD34+ selection. Ten days before
      autologous stem cell transplantation, the CD34+ fraction was cultured with
      MGDF+SCF for 10 days. After BEAM (BCNU, cyclophosphamide, cytarabine, and
      melphalan) chemotherapy, patients were reinfused with standard PBPC and ex vivo
      expanded cells. No toxicity was observed after reinfusion. The mean fold
      expansion was 9.27 for nucleated cells, 2 for CD34+ cells, 676 for CD41+ cells,
      and 627 for CD61+ cells. The median date of platelet transfusion independence was
      day 8 (range: 7-12). All patients received at least one platelet transfusion. In
      conclusion, ex vivo expansion of MK progenitors was feasible and safe, but this
      procedure did not prevent BEAM-induced thrombocytopenia. Future studies will
      determine if expansion of higher numbers of CD34+ cells towards the MK
      differentiation pathway will translate into a functional effect in terms of
      shortening of BEAM-induced thrombocytopenia.

PMID- 15489878
TI  - Bone marrow transplantation in young aspartylglucosaminuria mice: improved
      clearance of lysosomal storage in brain by using wild type as compared to
      heterozygote donors.

PMID- 15489879
TI  - Reduced-intensity conditioning using TBI (8 Gy), fludarabine, cyclophosphamide
      and ATG in elderly CML patients provides excellent results especially when
      performed in the early course of the disease.
AB  - Allogeneic bone marrow or stem cell transplantation is a curative therapeutic
      option for chronic myelogenous leukemia. In order to decrease the toxicity of the
      procedure, the dosage of total body irradiation was reduced from 12 to 8 Gy and
      subsequently the dose of cyclophosphamide from 120 to 80 mg/kg. The purine
      analogue fludarabine, ATG, cyclosporine A and a short course of methotrexate were
      given for immune suppression. So far, 35 elderly CML patients with sibling and
      unrelated donors have been transplanted. Transplant-related mortality at day +
      100 was 11%. After engraftment, all patients achieved a complete cytogenetic
      remission. Relapse occurred in 14% of the patients. The risk of relapse was
      significantly higher in those patients transplanted in second chronic or
      accelerated phase (P = 0.048). After a median follow-up of 30 months (range 12
      62), 63% of the patients are alive. Those patients transplanted within the first
      year from diagnosis had an overall survival of 79% (P = 0.049), emphasizing the
      benefit of early transplantation. Stepwise reduction of conditioning intensity
      resulted in stable engraftment, low relapse rates and encouraging overall
      survival in this high-risk patient group.

PMID- 15489880
TI  - Does haploidentical transplantation in children with primary immunodeficiencies
      have the potential to exploit donor NK cell alloreactivity?
AB  - Donor potential to exert NK cell alloreactivity has been shown to confer survival
      advantage in haploidentical hematopoietic cell transplantation for hematological
      malignancies. We investigated killer immunoglobulin receptor (KIR) ligand
      incompatibility in 40 children receiving haploidentical transplantation for
      primary immunodeficiencies. The conditioning regimen consisted of busulfan and
      cyclophosphamide. T-cell depletion of the graft used complement-dependent lysis
      or CD34+ selection. Two patients died in the first month. The remaining 38
      patients were divided into those with (n=13) and those without (n=25) donor
      potential to exert NK cell alloreactivity. Engraftment was similar in the two
      groups (61.5 and 64%, respectively). The incidence of grade II-IV acute graft
      versus-host disease (GVHD) tended to be lower in the group with donor potential
      to exert NK cell alloreactivity, but the difference was not significant. In
      conclusion, in this series of patients with primary immunodeficiencies, donor
      potential to exert NK cell alloreactivity was not associated with significant
      advantages in engraftment and prevention of acute GVHD.

PMID- 15489881
TI  - Autologous/syngeneic stem cell transplantation to treat refractory GvHD.
AB  - Severe graft-versus-host disease (GvHD) refractory to corticosteroids responds
      poorly to experimental treatment and is often fatal. Attempts have been made to
      'rescue' such patients by transfusing autologous cells in order to ablate the
      lymphoid component of the graft or to introduce regulatory cells capable of
      suppressing the GvHD. Here, we report details of eight patients with severe grade
      III-IV acute GvHD (n=7) or extensive chronic GvHD (n=1) who after failing a
      median of four lines of treatment were then treated with either autologous or
      syngeneic nucleated cell transfusions. Patients received standard conditioning
      (n=3), low intensity (n=2) or no conditioning (n=3) before the rescue procedure.
      In four of the five patients who received some form of conditioning, mixed
      chimerism or complete recipient hematopoiesis was restored. The GvHD resolved in
      four patients, of whom one died subsequently of multiorgan failure and two died
      of leukemia; one is still alive. A fifth patient had transient improvement in
      GvHD, which recurred when the corticosteroids were reduced. Three patients
      obtained no benefit from the procedure. We conclude that 'rescue' by transfusion
      of autologous or syngeneic nucleated cells may be valuable to treat severe
      refractory GvHD; the best approach to conditioning remains to be defined.

PMID- 15489882
TI  - Characteristics and outcome of patients developing endocarditis following
      hematopoietic stem cell transplantation.
AB  - Endocarditis is an uncommon complication of hematopoietic stem cell
      transplantation (HSCT). A retrospective review of 1547 patients who underwent
      HSCT in Vancouver between January 1986 and December 2001 was performed. In all,
      20 cases of endocarditis were identified (1.3% of all patients) with nine
      patients having received cryopreserved autologous stem cells, six stem cells from
      a histocompatible sibling and five patients stem cells from an unrelated donor.
      Five patients had endocarditis diagnosed while alive, a median of 6 months post
      HSCT, by transthoracic (four patients) or transesophageal (one patient)
      echocardiography. The remaining 15 cases of endocarditis were only identified
      post mortem. The mitral valve was the most frequently involved (10 patients)
      followed by the aortic valve (six patients); multivalvular disease was noted in
      five patients. Of the 11 affected allogeneic HSCT patients, 10 had previously
      developed acute graft-versus-host disease (GVHD). Causative organisms were
      identified in 11 patients, while nine additional cases were felt to be thrombotic
      in origin. Of the 20 patients, 19 died with the sole survivor alive 10 years
      following an aortic valve replacement. Endocarditis is an uncommon complication
      of HSCT usually involving the cardiac valves on the left side of the heart and is
      associated with a high mortality rate.

PMID- 15489883
TI  - Stem cell transplantation in follicular lymphoma: progress at last?
AB  - Follicular non-Hodgkin's lymphomas usually present in advanced stage and although
      frequently are chemotherapy-sensitive remain incurable using conventional
      approaches. Treatment options are evolving rapidly and now include targeted
      therapies such as monoclonal antibodies. Recent studies, including the EBMTR
      sponsored 'CUP Trial' (conventional Chemotherapy, Unpurged autograft, Purged
      autograft), demonstrate that for patients under age 60 years with recurrent
      chemotherapy-sensitive disease, autologous stem cell transplantation (ASCT)
      provides a survival benefit over conventional therapy. Allogeneic stem cell
      transplantation (alloSCT) has become a more effective option. Although
      incorporation of TBI into the preparative regimen may increase treatment-related
      mortality (TRM), relapses appear to be reduced compared to a chemotherapy-alone
      regimen. Reduced-intensity alloSCT procedures are now being performed at an
      increasing rate, in part due to a lower risk for TRM. Until more data are
      available, however, reduced-intensity alloSCT should be considered only in cases
      where myeloablative conditioning is contra-indicated. There are no clear means
      for choosing ASCT vs alloSCT, a decision influenced by the amount of residual
      tumor, disease-responsiveness, degree of marrow involvement and extent of prior
      chemotherapy. ASCT or alloSCT in first remission remains an investigational
      procedure. Future considerations include incorporation of novel preparative
      regimens, in vitro purging techniques, antilymphoma vaccines, post transplant
      immunotherapy and ex vivo-manipulated donor lymphocyte infusions.

PMID- 15489884
TI  - Regulation of cyclin expression and cell cycle progression in breast epithelial
      cells by the helix-loop-helix protein Id1.
AB  - The helix-loop-helix protein Id1 has been implicated in regulating mammary
      epithelial cell proliferation and differentiation but the underlying molecular
      mechanisms are not well characterized. Under low serum conditions, ectopic
      expression of Id1, but not Id2, allowed continued proliferation of immortalized
      mammary epithelial cells and breast cancer cells. Conversely, downregulation of
      Id1 impaired proliferation. The effects of short interfering RNA (siRNA)-mediated
      downregulation of Id1 were the same as those following downregulation of c-Myc:
      decreased expression of cyclins D1 and E, reduced phosphorylation of pRb at
      Ser780 (a site targeted by cyclin D1-Cdk4) and reduced cyclin E-Cdk2 activity.
      Decreased cyclin D1 expression was an early response to Id1 antisense
      oligonucleotide treatment. Inhibition of c-Myc function by siRNA, antisense
      oligonucleotides or a dominant repressor resulted in downregulation of Id1, while
      ectopic expression of c-Myc resulted in rapid induction of Id1, suggesting that
      Id1 may be downstream of c-Myc. These data indicate that in mammary epithelial
      cells, Id1 has cell cycle regulatory functions that are similar to those of c
      Myc, and suggest that cyclin D1 may be involved in Id1 regulation of cell cycle
      progression.

PMID- 15489885
TI  - Fatty acid synthase inhibitors are chemopreventive for mammary cancer in neu-N
      transgenic mice.
AB  - High levels of fatty acid synthase (FAS) have been found in cancer precursor
      lesions of the colon, stomach, esophagus, oral cavity, prostate, and breast.
      Inhibition of FAS with C75 has led to a significant antitumor effect in both
      human breast and prostate cancer xenografts. Recently, HER2/neu, which has also
      been identified in preneoplastic breast lesions, has been shown to regulate FAS
      expression through the PI3K/Akt signal transduction pathway rendering them
      susceptible to FAS inhibition. Utilizing the neu-N transgenic mouse model of
      mammary cancer, weekly treatment of the neu-N mice with C75 (30 mg/kg) for 10
      weeks significantly delayed tumor progression. Only 20% of the C75-treated
      transgenic mice developed mammary carcinoma by 220 days, compared to 50% in the
      vehicle control animals. Two C75-treated animals never developed mammary cancer.
      Analysis of mammary tissue following 10 weeks of C75 treatment revealed a
      significant delay in mammary maturation as manifested by a reduction of the
      number and caliber of mammary ducts and budding epithelial structures. Apoptotic
      changes were increased, DNA synthesis was decreased, and the expressions of FAS,
      neu, Akt, phospho-Akt, and p21(waf1) were all decreased when compared to vehicle
      controls and FVB/N mice. Importantly, these effects were restricted to the breast
      epithelial cells that overexpressed neu, not involving other normal duct
      structures in the skin, liver, or kidney. C247, an FAS inhibitor chemically
      distinct from C75, significantly delayed mammary maturation similar to C75. Thus,
      pharmacological inhibition of FAS affects the expression of key oncogenes
      involved in both cancer development and maintenance of the malignant phenotype.
      Moreover, these data identify FAS as a potential novel drug target for breast
      cancer chemoprevention.

PMID- 15489886
TI  - Molecular signature of oncogenic ras-induced senescence.
AB  - Senescence irreversibly arrests the proliferation of cells that have sustained
      significant cellular stress. Replicative senescence, due to the shortening and
      dysfunction of telomeres, appears to provide a barrier to the immortalization of
      cells and development of cancer. In normal human fibroblasts, senescence induced
      by oncogenic H-ras displays a nearly identical cellular phenotype to that of
      replicative senescence, suggesting the activation of a common senescence
      mechanism. In this study, we investigated the gene expression profile of
      oncogenic H-ras-induced senescent human diploid fibroblasts. We found altered
      gene expression of various cell cycle regulators in both oncogenic H-ras-induced
      senescent cells and replicative senescent cells. Similar to replicative senescent
      cells, H-ras-induced senescent cells exhibited specific downregulation of genes
      involved in G2/M checkpoint control and contained tetraploid cells that were
      arrested in a G1 state. This observation suggests that the inactivation of G2/M
      checkpoints may be involved in senescence and may play a role in the generation
      of senescent G1 tetraploid cells. Lastly, we have identified two genes,
      topoisomerase IIalpha and HDAC9, whose expression was specifically altered under
      several conditions associated with senescence, suggesting that these two
      molecules may be novel biomarkers for senescent human fibroblasts.

PMID- 15489887
TI  - Huntingtin interacting protein 14 is an oncogenic human protein: palmitoyl
      acyltransferase.
AB  - Protein palmitoyltransferases (PATs) represent an exciting new target for
      anticancer drug design due to their pivotal roles in the subcellular localization
      of a number of oncogenes. We show that the Huntingtin interacting protein 14
      (HIP14) is a PAT with a preference for the farnesyl-dependent palmitoylation
      motif found in H- and N-RAS. Characterization of HIP14 in mouse cells has
      revealed that it has the ability to induce colony formation in cell culture,
      anchorage-independent growth, and tumors in mice. Activity of the enzyme and its
      ability to transform cells is dependent on critical residues in the active site
      of the enzyme.

PMID- 15489888
TI  - Nonsteroidal anti-inflammatory agents differ in their ability to suppress NF
      kappaB activation, inhibition of expression of cyclooxygenase-2 and cyclin D1,
      and abrogation of tumor cell proliferation.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin have been shown to
      suppress transcription factor NF-kappaB, which controls the expression of genes
      such as cyclooxygenase (COX)-2 and cyclin D1, leading to inhibition of
      proliferation of tumor cells. There is no systematic study as to how these drugs
      differ in their ability to suppress NF-kappaB activation and NF-kappaB-regulated
      gene expression or cell proliferation. In the present study, we investigated the
      effect of almost a dozen different commonly used NSAIDs on tumor necrosis factor
      (TNF)-induced NF-kappaB activation and NF-kappaB-regulated gene products, and on
      cell proliferation. Dexamethasone, an anti-inflammatory steroid, was included for
      comparison with NSAIDs. As indicated by DNA binding, none of the drugs alone
      activated NF-kappaB. All compounds inhibited TNF-induced NF-kappaB activation,
      but with highly variable efficacy. The 50% inhibitory concentration required was
      5.67, 3.49, 3.03, 1.25, 0.94, 0.60, 0.38, 0.084, 0.043, 0.027, 0.024, and 0.010
      mM for aspirin, ibuprofen, sulindac, phenylbutazone, naproxen, indomethacin,
      diclofenac, resveratrol, curcumin, dexamethasone, celecoxib, and tamoxifen,
      respectively. All drugs inhibited IkappaBalpha kinase and suppressed IkappaBalpha
      degradation and NF-kappaB-regulated reporter gene expression. They also
      suppressed NF-kappaB-regulated COX-2 and cyclin D1 protein expression in a dose
      dependent manner. All compounds inhibited the proliferation of tumor cells, with
      50% inhibitory concentrations of 6.09, 1.12, 0.65, 0.49, 1.01, 0.19, 0.36, 0.012,
      0.016, 0.047, 0.013, and 0.008 mM for aspirin, ibuprofen, sulindac,
      phenylbutazone, naproxen, indomethacin, diclofenac, resveratrol, curcumin,
      dexamethasone, celecoxib, and tamoxifen, respectively. Overall these results
      indicate that aspirin and ibuprofen are least potent, while resveratrol,
      curcumin, celecoxib, and tamoxifen are the most potent anti-inflammatory and
      antiproliferative agents of those we studied.

PMID- 15489889
TI  - Molecular analysis integrating different pathways associated with androgen
      independent progression in LuCaP 23.1 xenograft.
AB  - After therapeutic hormone deprivation, most prostate cancer (PrCa) cells develop
      androgen-independent (AI) growth. PrCa is highly heterogeneous and multifocal,
      suggesting that several molecular processes or pathways may be contributing to
      AI. The human LuCaP 23.1 xenograft model retains clinical hallmarks of PrCa,
      including heterogeneous growth, PSA production, androgen-responsiveness and
      progression to AI. In this work, we studied the effect of androgen depletion
      (castration) on the growth of LuCaP 23.1 xenografts. A total of 100 nude mice
      were implanted and analysed for their growth profiles before and after
      castration. By 11 and 15 weeks, tumours were harvested and assessed for molecular
      marker expression specific for PrCa. Prior to castration we found 37 fast growing
      (FG) tumours (948.9+/-76.9 mm(3)) and 63 slow growing (SG) tumours (229.6+/-18.4
      mm(3)), a previously undescribed result for this PrCa model. Quantitative RT-PCR
      showed that in comparison to SGs, FGs contained high HER1, uPA and thymidilate
      synthetase (TS) expression with low levels of 5alpha-reductase 2 mRNA. All FG
      tumours progressed rapidly to AI growth 5 weeks after castration (FG-P). In SG
      castrated tumours, 66% of tumours (SG-P) showed retarded progression (by 12
      weeks) to AI, whereas 34% responded to castration (SG-R). Molecular analysis
      permitted us to define distinct molecular profiles integrating different pathways
      associated with AI progression. FG-P, and a subgroup of SG-P tumours, presented
      significantly high levels of peptidylglycine alpha-amidating monooxygenase (PAM),
      HER1, HER2, TS, and uPA mRNA, all of which correlated with AR expression. The
      second subgroup of SG-P tumours showed overexpression of the antiapoptotic gene
      Bcl-2. A third subgroup of SG-P tumours showed significant expression of hypoxia
      related gene (adrenomedullin) after castration. This work permitted to define
      distinct molecular profiles related to different AI growth in the LuCaP 23.1
      xenograft.

PMID- 15489890
TI  - Role of the BLT2, a leukotriene B4 receptor, in Ras transformation.
AB  - Oncogenic Ras is known to drive both the Rac and Raf-MAP-kinase pathways, which
      act in concert to cause cell transformation. Unlike the Raf-MAP-kinase cascade,
      however, the downstream elements of Rac pathway are not fully understood.
      Previously, we showed that cytosolic phospholipase A2 (cPLA2) and subsequent
      metabolism of arachidonic acid act downstream of Rac to mediate the
      transformation signaling induced by Ha-Ras(V12). In the present study, we
      observed that leukotriene B4 (LTB4) and its synthetic enzymes as well as BLT2,
      the low-affinity LTB4 receptor, are all elevated in Ha-Ras(V12)-transformed
      cells. In addition, the malignant phenotypes of Ras-transformed cells were
      markedly inhibited by BLT2 blockade, as was their tumorigenicity in vivo.
      Finally, in situ hybridization analysis revealed that expression of BLT2 is
      significantly upregulated in a variety of human cancers. Taken together, our
      results suggest that an LTB4-BLT2-linked cascade plays a crucial mediatory role
      in the cell transformation induced by oncogenic Ha-Ras(V12), possibly acting
      downstream of Rac-cPLA2.

PMID- 15489891
TI  - The apoptotic pathway triggered by the Fhit protein in lung cancer cell lines is
      not affected by Bcl-2 or Bcl-x(L) overexpression.
AB  - The expression of the tumour suppressor protein fragile histidine triad (Fhit) is
      often impaired in many human cancers and its restoration in Fhit-negative cancer
      cell lines suppresses tumorigenicity and induces apoptosis. Although the
      proapoptotic function of Fhit is well documented, little is known about its
      precise mechanism of action and further studies are needed in order to elucidate
      the putative therapeutic properties of this protein. To this end, we have
      engineered the lung cancer cell line NCI-H460 in order to express different
      molecules involved in the control of apoptotic pathways. Infection of these cells
      with an adenoviral vector transducing the Fhit gene (Ad-Fhit) revealed that
      complete protection from apoptosis was conferred by the inhibitor of caspases
      Cytokine response modifier A (CrmA) and by a dominant-negative form of the
      adapter protein Fas-associated death domain (FADD) and partial protection by a
      dominant-negative form of caspase-8, while cells over expressing mitochondrial
      mediators of the apoptotic response such as Bcl-2 or Bcl-x(L) that are resistant
      to treatment with cisplatin, remained highly susceptible to cell death triggered
      by Fhit gene transfer. In line to what was observed in H460 cells, Ad-Fhit
      efficacy was not affected by Bcl-2 overexpression also in two other lung cancer
      cell lines (A549 and Calu-1). Analysis of cytochrome c release also confirmed
      that in Bcl-2- or Bcl-x(L)-expressing cells apoptosis could be detected by
      terminal deoxynucleotidyl-transferase mediated dUTP nick-end labelling (TUNEL)
      assay before any evidence of mitochondrial membrane perturbation. In conclusion,
      our analysis indicates that the Fhit protein exerts its oncosuppressor activity
      through induction of an apoptotic mechanism that seems to be FADD dependent,
      caspase-8 mediated and independent from mitochondrial amplification.

PMID- 15489892
TI  - Inhibition of p53-mediated transcriptional responses by mithramycin A.
AB  - In the present work, we show that mithramycin A, a drug that is currently used
      for the treatment of patients with Paget's disease of the bone as well as with
      several forms of cancer, is a strong activator of the tumor suppressor p53
      protein in human hepatoma cells. The time course of p53 activation by mithramycin
      A was similar to the known chemotherapeutic compound 5-fluorouracil (5-FU). Both
      5-FU and mithramycin A induced site-specific phosphorylation of p53 at serine 15.
      However, in contrast to 5-FU, mithramycin A failed to activate p53 target genes
      including the cell cycle inhibitor p21Cip1 gene as well as the proapoptotic genes
      PUMA (p53-upregulated mediator of apotosis) and BAK (bcl2-homologous
      antagonist/killer) and blocked the induction of the above genes by 5-FU. Using
      transactivation assays in Sp1-deficient cells, we showed that mithramycin A
      inhibited the transcriptional activation of the p21Cip1 and PUMA promoters by Sp1
      and p53. Using chromatin immunoprecipitation assays and a novel protein-protein
      interaction assay based on biotinylation in vivo, we established that 5-FU
      enhanced the formation of p53-Sp1 complexes in solution and the subsequent
      recruitment of both factors to the p21Cip1 promoter. Mithramycin A also enhanced
      the recruitment of p53 to the distal p21Cip1 promoter but totally blocked the
      recruitment of Sp1 to the proximal p21Cip1 promoter. Our findings suggest that
      inhibition of Sp1 binding to the promoters of several p53 target genes, such as
      the p21Cip1 gene as well as certain proapoptotic genes, by mithramycin A,
      prevents the transcriptional induction of these genes by p53 and propose a
      mechanism that could account for some of the tumor suppressing and antiapoptotic
      effects of mithramycin A.

PMID- 15489893
TI  - ST18 is a breast cancer tumor suppressor gene at human chromosome 8q11.2.
AB  - We have identified a gene, ST18 (suppression of tumorigenicity 18, breast
      carcinoma, zinc-finger protein), within a frequent imbalanced region of
      chromosome 8q11 as a breast cancer tumor suppressor gene. The ST18 gene encodes a
      zinc-finger DNA-binding protein with six fingers of the C2HC type (configuration
      Cys-X5-Cys-X12-His-X4-Cys) and an SMC domain. ST18 has the potential to act as
      transcriptional regulator. ST18 is expressed in a number of normal tissues
      including mammary epithelial cells although the level of expression is quite low.
      In breast cancer cell lines and the majority of primary breast tumors, ST18 mRNA
      is significantly downregulated. A 160 bp region within the promoter of the ST18
      gene is hypermethylated in about 80% of the breast cancer samples and in the
      majority of breast cancer cell lines. The strong correlation between ST18
      promoter hypermethylation and loss of ST18 expression in tumor cells suggests
      that this epigenetic mechanism is responsible for tumor-specific downregulation.
      We further show that ectopic ST18 expression in MCF-7 breast cancer cells
      strongly inhibits colony formation in soft agar and the formation of tumors in a
      xenograft mouse model.

PMID- 15489894
TI  - Distinct profiles of critically short telomeres are a key determinant of
      different chromosome aberrations in immortalized human cells: whole-genome
      evidence from multiple cell lines.
AB  - Chromosomal aberrations are common in cancers. However, the search for
      chromosomal aberrations leading to development of specific solid tumors has been
      severely hindered because the majority of solid tumors have complex chromosomal
      aberrations that differ within the same tumor types. A similar phenomenon exists
      in immortalized cell lines. The underlying mechanisms driving these diverse
      aberrations are largely unknown. Telomeres play crucial roles in protecting the
      integrity of eucaryotic chromosomes and maintaining genomic stability of human
      cells. Telomere lengths on individual chromosomes in normal human somatic cells
      are heterogeneous and undergo progressive shortening with aging process. In this
      study, for the first time, a molecular cytogenetic method using sequential
      telomere quantitative fluorescence in situ hybridization and spectral karyotyping
      on the same human metaphases was applied successfully to examine the dynamic
      profiles of individual telomere shortening and their relationship to chromosome
      aberrations in multiple human cell lines undergoing immortalization. Human
      ovarian surface epithelial cells and esophageal epithelial cells were
      immortalized by the expression of HPV16 E6 and E7, which drive cells to
      proliferate by inactivating p53 and Rb genes. In these cell lines, we
      consistently detected large-scale differences in telomere signal intensities not
      only among nonhomologous chromosome arms but also between some homologous
      chromosome arms. The cell lines derived from different donors had different
      profiles of critically short telomeres (lacking telomere signals). Strikingly,
      the different profiles of chromosomal structural aberrations in multiple
      immortalized cell lines were highly significantly associated with the distinct
      distributions of critically short telomeres in whole-genome. Since cellular
      immortalization is one of the hallmarks of cancer, our findings suggest that
      distinct profiles of critically short telomeres in different human individuals
      might play an essential role in determining the complex and individual-specific
      chromosomal structural aberrations in human solid tumors.

PMID- 15489895
TI  - Characterization of gene expression in mucinous cystic neoplasms of the pancreas
      using oligonucleotide microarrays.
AB  - Mucinous cystic neoplasms (MCNs) of the pancreas are uncommon neoplasms usually
      located in the body or tail of the pancreas and usually in females (>90% of
      cases). Clinically, they are often misdiagnosed as non-neoplastic pseudocysts
      leading to failed opportunities for curative resection. To better understand the
      biology of MCNs and to identify markers of the disease, we performed global gene
      expression profiling of MCNs using oligonucleotide microarrays. Using laser
      capture microdissection applied to frozen sections, RNA was extracted from the
      neoplastic epithelium of MCNs, from the adjacent 'ovarian-type' stroma of MCNs,
      from histologically normal pancreatic ductal epithelium, from pancreatic acinar
      tissue and from fibrous stroma in pancreata affected by chronic pancreatitis.
      Each RNA sample was subjected to two rounds of linear amplification followed by
      hybridization with U133A gene chips (Affymetrix). The expression patterns of
      selected genes were confirmed by quantitative RT-PCR and by immunohistochemistry
      using tissue microarrays containing 19 resected MCNs. A total of 114 known genes
      were overexpressed in the neoplastic epithelium compared to normal pancreatic
      ductal epithelium (>3-fold) including S100P, PSCA, c-myc, STK6/STK15, cathepsin E
      and pepsinogen C. Activation of the Notch pathway in the epithelial component of
      MCNs was evident by the demonstration of overexpression of Jagged1 and the
      downstream Notch pathway member Hes1. In the 'ovarian-type' stroma, several genes
      involved in estrogen metabolism were overexpressed including STAR and ESR1 genes.
      Some of the genes identified as overexpressed in these neoplasms may be useful as
      markers that can distinguish MCNs from non-neoplastic pancreatic cystic lesions.

PMID- 15489896
TI  - Defining minimum genomic regions of imbalance involved in testicular germ cell
      tumors of adolescents and adults through genome wide microarray analysis of cDNA
      clones.
AB  - Identifying changes in DNA copy number can pinpoint genes that may be involved in
      tumor development. Here we have defined the smallest overlapping regions of
      imbalance (SORI) in testicular germ cell tumors other than the 12p region, which
      has been previously investigated. Definition of the regions was achieved through
      comparative genomic hybridization (CGH) analysis of a 4559 cDNA clone microarray.
      A total of 14 SORI were identified, which involved at least five of the 11
      samples analysed. Many of these refined regions were previously reported using
      chromosomal or allelic imbalance studies. The SORI included gain of material from
      the regions 4q12, 17q21.3, 22q11.23 and Xq22, and loss from 5q33, 11q12.1,
      16q22.3 and 22q11. Comparison with parallel chromosomal CGH data supported
      involvement of most regions. The various SORI span between one and 20 genes and
      highlight potential oncogenes/tumor suppressor genes to be investigated further.

PMID- 15489897
TI  - PKC-eta mediates glioblastoma cell proliferation through the Akt and mTOR
      signaling pathways.
AB  - We previously demonstrated that protein kinase C-eta (PKC-eta) mediates a phorbol
      12-myristate-13-acetate (PMA)-induced proliferative response in human
      glioblastoma (GBM) cells. In this report, we show that PMA-stimulated activation
      of PKC-eta in U-251 GBM cells resulted in activation of both Akt and the
      mammalian target of rapamycin (mTOR) signaling pathways and an increase in cell
      proliferation. Expression of a kinase dead PKC-eta (PKC-etaKR) construct reduced
      the basal and PMA-evoked proliferation of PKC-eta-expressing U-251 GBM cells, as
      well as abrogated the PMA-induced activation of Akt, mTOR, and the mTOR targets
      4E-BP1 and STAT-3. Treatment of cells with the PI-3 kinase inhibitor LY294002 (10
      muM) or the mTOR inhibitor rapamycin (10 nM) also reduced PMA-induced
      proliferation and cell-cycle progression. Expression of a constitutively active
      PKC-eta (PKC-etaDeltaNPS) construct in a GBM cell line with no endogenous PKC-eta
      (U-1242) also provided evidence that PKC-eta targets the Akt and mTOR signaling
      pathways. Moreover, activation of 4E-BP1 and STAT-3 in both PMA-treated U-251 and
      PKC-etaDeltaNPS-expressing U-1242 GBM cells was inhibited by rapamycin. However,
      activation of Akt, but not mTOR was inhibited by the PI-3 kinase inhibitor
      LY294002. This study identifies Akt and mTOR as downstream targets of PKC-eta
      that are involved in GBM cell proliferation.

PMID- 15489898
TI  - Altered regulation of Src upon cell detachment protects human lung adenocarcinoma
      cells from anoikis.
AB  - Src plays an important role in cell proliferation, differentiation, adhesion, and
      migration. Altered Src activity has been strongly implicated in the development,
      growth, progression, and metastasis of human cancers. We have analysed the change
      and regulation of Src upon cell detachment in anoikis-resistant human lung
      adenocarcinoma cells and compared with that of relatively normal and anoikis
      sensitive epithelial cells. We found that Src activity was increased in the
      anoikis-resistant lung tumor cells when they were detached and cultured in
      suspension. The detachment-induced Src activation in the tumor cells compensates
      for the loss of cell survival signals caused by disruption of cell--matrix
      interactions and contributes to anoikis resistance of the tumor cells. Pyk2,
      rather than PI 3K/Akt or Erk, appears to be the key downstream effecter of Src in
      mediating the cell survival signals. The increased Src activity is mainly due to
      the phosphorylation of Tyr-419, rather than the dephosphorylation of Tyr-530 of
      Src protein. PDGFR, not FAK or EGFR, appears to be the upstream protein tyrosine
      kinase responsible for the detachment-induced Src activation in the lung tumor
      cells. The increased Src activity upon cell detachment may contribute to the
      metastasis potential of malignant tumors.

PMID- 15489899
TI  - Regulation of the cyclin A1 protein is associated with its differential
      subcellular localization in hematopoietic and leukemic cells.
AB  - An important role of the cell cycle regulatory protein cyclin A1 in the
      development of acute myeloid leukemia (AML) was previously demonstrated in a
      transgenic mouse model. We have now turned our attention to study specific
      aspects of the activity and subcellular distribution of cyclin A1 using bone
      marrow samples from normal donors and patients with AML, as well as leukemic cell
      lines. We show that the localization of cyclin A1 in normal hematopoietic cells
      is nuclear, whereas in leukemic cells from AML patients and cell lines, it is
      predominantly cytoplasmic. In leukemic cell lines treated with all-trans retinoic
      acid (ATRA), cyclin A1 localized to the nucleus. Further, there was a direct
      interaction between cyclin A1 and cyclin-dependent kinase 1, as well as a major
      ATRA receptor, RARalpha, in ATRA-treated cells but not in untreated leukemic
      cells. Our results indicate that the altered intracellular distribution of cyclin
      A1 in leukemic cells correlates with the status of the leukemic phenotype.

PMID- 15489900
TI  - The N-terminus of a novel isoform of human iASPP is required for its cytoplasmic
      localization.
AB  - ASPP1 and ASPP2 are both proteins that interact with p53 and enhance its ability
      to induce apoptosis by selectively elevating the expression of proapoptotic p53
      responsive genes. iASPP(RAI) is a third member of the family that is the most
      conserved inhibitor of p53-mediated apoptosis. Here, we have described iASPP, a
      longer form of iASPP(RAI), which at 828 amino acids is more than twice the size
      of iASPP(RAI). Using two antibodies that recognize both iASPP and iASPP(RAI), we
      report that this longer form of iASPP is the predominant form of the molecule
      expressed in cells. Like iASPP(RAI), iASPP also binds to p53 and inhibits
      apoptosis induced by p53 overexpression. However, whereas iASPP(RAI) is
      predominantly nuclear, the N-terminus of iASPP is entirely cytoplasmic, and the
      longer iASPP is located in both the cytoplasm and the nucleus. The effect upon
      subcellular localization of the longer N-terminus of iASPP means that this new,
      longer form of the molecule may be subject to greater regulation and provides
      another layer in the control of p53-induced apoptosis.

PMID- 15489901
TI  - Williams-Beuren syndrome critical region-5/non-T-cell activation linker: a novel
      target gene of AML1/ETO.
AB  - The chromosomal translocation t(8;21) fuses the AML1 (RUNX1) gene on chromosome
      21 and the ETO gene on chromosome 8 in human acute myeloid leukemias (AMLs),
      resulting in expression of the chimeric transcription factor AML1/ETO. AML1/ETO
      mediated dysregulation of target genes critical for hematopoietic differentiation
      and proliferation is thought to contribute to the leukemic phenotype. Several
      mechanisms, including recruitment of histone deacetylases (HDACs) to AML1 target
      genes, may be responsible for altered gene expression. We used an ecdysone
      inducible expression system in the human monoblastic U-937 cell line to isolate
      genes that were differentially expressed upon induction of AML1/ETO expression.
      By representational difference analysis (cDNA-RDA), we identified 26 genes whose
      expression levels were significantly modulated following AML1/ETO induction for
      48 h. None of these genes has previously been described as a target of AML1, ETO
      or AML1/ETO. One gene downregulated by AML1/ETO in vitro, Williams Beuren
      syndrome critical region 5 (WBSCR5), was expressed in primary t(8;21)-negative
      AML blasts but not in primary t(8;21)-positive AML blasts, strongly implying a
      role of this gene in the phenotype of t(8;21)-positive AML. Four upregulated and
      four downregulated genes were further studied with all-trans-retinoic acid
      (ATRA), an inducer of differentiation of U-937 cells, and Trichostatin A (TSA),
      an HDAC inhibitor. Three out of eight genes including WBSCR5 were regulated
      during ATRA-induced monocytic differentiation of U-937 cells, however, none of
      them antagonistically, upon both ATRA treatment and AML1/ETO induction. AML1/ETO
      associated dysregulation of gene expression was not mediated by a TSA-sensitive
      mechanism. The identified genes provide a useful model to study the mechanism by
      which the AML1/ETO fusion protein exerts its function in transcriptional
      dysregulation in AML. The possible role of WBSCR5 in normal and malignant
      hematopoiesis warrants further study.

PMID- 15489902
TI  - Prostate cancer is characterized by epigenetic silencing of 14-3-3sigma
      expression.
AB  - In order to identify tumor suppressive genes silenced by CpG methylation in
      prostate carcinoma (PCa), we determined genome-wide expression changes after
      pharmacological reversal of CpG methylation-mediated transcriptional repression
      in three PCa cell lines using microarray analysis. Thereby, epigenetic silencing
      of the 14-3-3sigma gene was detected in the cell line LNCaP. 14-3-3sigma encodes
      a p53-regulated inhibitor of cell cycle progression. Laser microdissection was
      used to isolate different cell types present in diseased prostatic tissue.
      Subsequent methylation-specific PCR analysis showed CpG methylation of 14-3
      3sigma in all 41 primary PCa samples analysed, which was accompanied by a
      decrease or loss of 14-3-3sigma protein expression. In contrast, normal prostate
      epithelial and benign prostate hyperplasia cells showed high levels of 14-3
      3sigma expression. PCa-precursor lesions (prostatic intraepithelial neoplasia)
      also displayed decreased levels of 14-3-3sigma expression in luminal cells, which
      are known to contain shortened telomeres. RNA interference-mediated inactivation
      of 14-3-3sigma compromised a DNA damage-induced G(2)/M arrest in the PCa cell
      line PC3. The generality of CpG methylation and downregulation of 14-3-3sigma
      expression in PCa suggests that it significantly contributes to the formation of
      PCa, potentially by allowing the escape from a DNA damage-induced arrest elicited
      by telomere shortening.

PMID- 15489903
TI  - The interaction of p53 with replication protein A mediates suppression of
      homologous recombination.
AB  - The tumor suppressor protein p53 is emerging as a central regulator of homologous
      recombination (HR) processes and DNA replication. P53 may downregulate HR through
      multiple mechanisms including the reported associations with the Rad51 and Rad54
      recombinases, and the BLM and WRN helicases. Here, we investigated whether the
      interaction of p53 with human replication protein A (RPA) is necessary for the
      regulation of HR. By employing a plasmid-based HR assay in p53-null H1299 lung
      carcinoma cells, we studied the HR-suppressing properties of a panel of p53
      mutants, which varied in their ability to interact with RPA. Both wild-type p53
      and a transactivation-deficient p53 mutant (L22Q/W23S) suppressed HR and
      prevented RPA binding to ssDNA in vitro and in vivo. Conversely, p53 mutations
      that specifically disrupt the RPA-binding domain, while not compromising p53
      transactivation function (D48H/D49H and W53S/F54S), did not affect HR.
      Suppression of HR was also not seen with missense mutations in the p53 core
      domain (His175 and His273), which retained the ability to interact with RPA,
      suggesting that the disruption of additional binding interactions of p53, for
      example, with Rad51 or recombination intermediates, also impacts on HR. We
      hypothesize that sequestration of RPA by p53 at the sites of recombination is one
      means by which p53 can inhibit HR processes. Our data support and extend the
      previously formulated 'dual model' of p53's role as guardian of the genome.

PMID- 15489904
TI  - Deep genomics in shallow times: the finished sequence of human chromosomes 13 and
      19.

PMID- 15489905
TI  - Congenital afibrinogenaemia caused by uniparental isodisomy of chromosome 4
      containing a novel 15-kb deletion involving fibrinogen Aalpha-chain gene.
AB  - Among rare inherited deficiencies of coagulation factors, congenital
      afibrinogenaemia is characterised by the lack of fibrinogen in plasma. In the
      last few years, several genetic defects underlying afibrinogenaemia (mostly point
      mutations) have been described in the fibrinogen gene cluster. In this study, the
      molecular basis responsible for afibrinogenaemia in a Thai proband was defined.
      Point mutation screening was accomplished by directly sequencing the three
      fibrinogen genes. The impossibility to amplify fibrinogen Aalpha-chain gene (FGA)
      exons 5 and 6 suggested the presence of a homozygous deletion. A specific long
      range PCR assay enabled the identification of a novel 15-kb deletion,
      representing the largest afibrinogenaemia-causing deletion described so far.
      Direct sequencing of the deletion junction allowed mapping of the breakpoints in
      FGA intron 4 and in the intergenic region between Aalpha- and Bbeta-chain genes.
      Since the mutation was inherited only from the mother and nonpaternity was ruled
      out, a maternal uniparental disomy (UPD) was hypothesised. UPD test, carried out
      with markers covering the whole chromosome 4, revealed that maternal isodisomy
      was responsible for homozygosity of the 15-kb deletion in the proband. The
      apparently normal phenotype of the proband, except for afibrinogenaemia, suggests
      that UPD for chromosome 4 is clinically silent. This represents the first case of
      a documented complete isodisomy of chromosome 4 causing the phenotypic expression
      of a recessive disorder. In silico analyses of the regions surrounding the
      breakpoints suggested that the 15-kb deletion might have originated from an
      inappropriate repair of a double-strand break by the nonhomologous end joining
      mechanism.

PMID- 15489908
TI  - Src family kinases, key regulators of signal transduction.
AB  - The Src family of protein tyrosine kinases (SFKs) plays key roles in regulating
      signal transduction by a diverse set of cell surface receptors in the context of
      a variety of cellular environments. SFKs have evolved many ingenious molecular
      strategies to couple receptors with the cytoplasmic signaling machinery. The
      contributions to this issue of ONCOGENE describe how this machinery regulates
      fundamental cellular processes, including cell growth, differentiation, cell
      shape, migration and survival, and specialized cell signals. The pleiotropic
      functions of Src and Src family members underscore the importance of these
      kinases and explain why many of the members of this family have been identified
      as cellular oncogenes. In this volume, we have attempted to provide the reader
      with an overview of the current understanding of the function of Src family
      kinases in the regulation of selected cellular signaling pathways.

PMID- 15489909
TI  - The road to Src.
AB  - More than a quarter of a century has elapsed since the identification of the c
      src proto-oncogene. During that period, we have learned that cancer arises as the
      result of mutations in proto-oncogenes and tumor suppressor genes, and we are now
      seeing the first fruits of these discoveries, in the form of targeted therapies
      directed against activated tyrosine kinases such as Bcr-Abl, c-Kit and the EGF
      receptor. But the discovery of the c-src proto-oncogene was in turn based on
      decades of study on an avian RNA tumor virus, Rous sarcoma virus (RSV). Here I
      review the work that led up to the identification of the RSV transforming gene
      and its protein product, and how this information in turn led to the discovery of
      cellular Src.

PMID- 15489910
TI  - Structure and regulation of Src family kinases.
AB  - Src family kinases are prototypical modular signaling proteins. Their conserved
      domain organization includes a myristoylated N-terminal segment followed by SH3,
      SH2, and tyrosine kinase domains, and a short C-terminal tail. Structural
      dissection of Src kinases has elucidated the canonical mechanisms of
      phosphotyrosine recognition by the SH2 domain and proline-motif recognition by
      the SH3 domain. Crystallographic analysis of nearly intact Src kinases in the
      autoinhibited state has shown that these protein interaction motifs turn inward
      and lock the kinase in an inactive conformation via intramolecular interactions.
      The autoinhibited Src kinase structures reveal a mode of domain assembly used by
      other tyrosine kinases outside the Src family, including Abl and likely Tec
      family kinases. Furthermore, they illustrate the underlying regulatory principles
      that have proven to be general among diverse modular signaling proteins. Although
      there is considerable structural information available for the autoinhibited
      conformation of Src kinases, how they may assemble into active signaling
      complexes with substrates and regulators remains largely unexplored.

PMID- 15489911
TI  - The interplay between Src and integrins in normal and tumor biology.
AB  - Src family nonreceptor protein tyrosine kinases transduce signals that control
      normal cellular processes such as cell proliferation, adhesion and motility.
      Normally, cellular Src is held in an inactive state, but in several cancer types,
      abnormal events lead to elevated kinase activity of the protein and cause
      pleiotropic cellular responses inducing transformation and metastasis. A
      prerequisite of the ability of a cancer cell to undergo metastasis into distant
      tissues is to penetrate surrounding extracellular matrices. These processes are
      facilitated by the integrin family of cell adhesion molecules. As is the case
      with Src, altered integrin activity or substrate affinity can contribute to the
      neoplastic phenotype. Therefore, understanding the interplay between Src and
      integrin function has been of intense interest over the past few years. This
      review focuses on the role of Src and integrin signaling in normal cells and how
      this is deregulated in human cancer. We will identify the key players in the
      integrin-mediated signaling pathways involved in cell motility and apoptosis,
      such as FAK, paxillin and p130(CAS), and discuss how Src signaling affects the
      formation of focal adhesions and the extracellular matrix.

PMID- 15489912
TI  - Emerging roles for p120-catenin in cell adhesion and cancer.
AB  - Although originally identified as a Src substrate, p120-catenin (p120) is now
      known to regulate cell-cell adhesion through its interaction with the cytoplasmic
      tail of classical and type II cadherins. New evidence indicates that p120
      regulates cadherin turnover at the cell surface, thereby controlling the amount
      of cadherin available for cell-cell adhesion. This function is necessary but not
      sufficient to promote strong adhesion, which is further controlled by signals
      acting on the amino-terminal p120 regulatory domain. p120 also modulates the
      activities of RhoA, Rac, and Cdc42, suggesting that along with other Src
      substrates, p120 regulates actin dynamics. Thus, p120 is a master regulator of
      cadherin abundance and activity, and likely participates in regulating the
      balance between adhesive and motile cellular phenotypes. This review summarizes
      recent progress in understanding mechanisms of p120 action, and discusses new
      implications with respect to roles for p120 in disease and cancer.

PMID- 15489913
TI  - The interplay between Src family kinases and receptor tyrosine kinases.
AB  - Src family tyrosine kinases (SFKs) are involved in a diverse array of
      physiological processes, as highlighted in this review. An overview of how SFKs
      interact with, and participate in signaling from, receptor tyrosine kinases
      (RTKs) is discussed. And also, how SFKs are activated by RTKs, and how SFKs, in
      turn, can activate RTKs, as well as how SFKs can promote signaling from growth
      factor receptors in a number of ways including participation in signaling
      pathways required for DNA synthesis, control of receptor turnover, actin
      cytoskeleton rearrangements and motility, and survival are discussed.

PMID- 15489914
TI  - Not so strange bedfellows: G-protein-coupled receptors and Src family kinases.
AB  - Src family nonreceptor tyrosine kinases are an integral component of the signal
      transduction apparatus employed by growth factor receptor tyrosine kinases. As
      such, their role in cellular growth control and malignant transformation has been
      the subject of intensive investigation. In contrast, classical G-protein-coupled
      receptor (GPCR) signaling involves activation of second messenger-regulated
      serine/threonine kinases or ion channels, and is primarily involved in
      neurotransmission and the short-term regulation of intermediary metabolism. Over
      the past decade, this strictly dichotomous model of transmembrane signaling has
      been challenged by the discovery that GPCRs also exert control over cellular
      growth, proliferation, and differentiation, and do so by stimulating tyrosine
      phosphorylation cascades. Several mechanisms, from the direct association of Src
      family kinases with GPCRs or receptor-associated proteins, to the transactivation
      of receptor tyrosine kinases and focal adhesion complexes by G-protein-mediated
      signals, permit GPCRs to activate Src family kinases. Conversely, Src activity
      plays a central role in controlling GPCR trafficking and effects on cell
      proliferation and cytoskeletal rearrangement. It is now clear that GPCRs and Src
      family kinases do not belong to separate, exclusive clubs. Rather, these strange
      bedfellows are intimately involved in multilayered forms of crosstalk that
      influence a host of cellular processes.

PMID- 15489915
TI  - Crosstalk between steroid receptors and the c-Src-receptor tyrosine kinase
      pathways: implications for cell proliferation.
AB  - Both steroids and growth factors stimulate proliferation of steroid-dependent
      tumor cells, and interaction between these signaling pathways may occur at
      several levels. Steroid receptors are typically classified as ligand-activated
      transcription factors, and steps by which they bind ligand, dimerize, recruit
      coregulatory molecules, and activate target gene transcription are well
      understood. Several steroid responses are functionally linked to c-Src or
      tyrosine kinase receptors, and the physiological impact and the precise molecular
      pathways involved in these responses are under intensive investigation. Ligand
      independent stimulation of steroid receptor-mediated transcription by growth
      factors is now believed to occur through activated protein kinases that
      phosphorylate the receptors and receptor coregulators. Recently, steroid hormones
      themselves have been shown to rapidly activate intracellular signaling cascades,
      via binding to cognate cytoplasmic or membrane-associated receptors. In some
      contexts, steroid receptors interact directly with c-Src and other cytoplasmic
      signaling molecules, such as Shc, PI3K, and p130 Cas. Crosstalk between growth
      factors and steroids in both the cytoplasm and nucleus could have profound impact
      on complex biological processes such as cell growth, and play a significant role
      in the treatment of steroid-dependent cancers. The potential roles of
      progesterone and estrogen receptors in this crosstalk are discussed in this
      review.

PMID- 15489916
TI  - Function of the Src-family kinases, Lck and Fyn, in T-cell development and
      activation.
AB  - The function of the Src-family kinases (SFKs) Lck and Fyn in T cells has been
      intensively studied over the past 15 years. Animal models and cell line studies
      both indicate a critical role for Lck and Fyn in proximal T-cell antigen receptor
      (TCR) signal transduction. Recruited SFKs phosphorylate TCR ITAMs (immunoreceptor
      tyrosine-based activation motifs) in the CD3 and zeta chains, which then serve as
      docking sites for Syk-family kinases. SFKs then phosphorylate and activate the
      recruited Syk-family kinase. Lck and Fyn are spatially segregated in cell
      membranes due to differential lipid raft localization, and may undergo sequential
      activation. In addition to the CD4 and CD8 coreceptors, a recently described
      adaptor, Unc119, may link SFKs to the TCR. CD45 and Csk provide positive and
      negative regulatory control of SFK functions, respectively, and Csk is
      constitutively bound to the transmembrane adapter protein, PAG/Cbp. TCR-based
      signaling is required at several stages of T-cell development, including at least
      pre-TCR signaling, positive selection, peripheral maintenance of naive T cells,
      and lymphopenia-induced proliferation. SFKs are required for each of these TCR
      based signals, and Lck seems to be the major contributor.

PMID- 15489917
TI  - Src-family kinases in B-cell development and signaling.
AB  - The Src-family protein tyrosine kinases (SFKs) are known to play key roles in
      initiating signal transduction by the B-cell antigen receptor (BCR). In addition,
      numerous studies have shown that this family of molecules also contributes to
      signaling by BCR surrogates during B-lymphocyte lineage development and
      maturation. Paradoxically, ablation of SFKs not only results in obvious defects
      in B-cell development but also in the onset of autoimmunity. Thus SFKs, most
      notably Lyn, play both activating and inhibitory roles in B-cell function.
      Confounding analyses of SFK function in B cells is the varied coexpression of
      family members that mediate redundant as well as unique functions. In this
      review, we will focus mainly on the role of Lyn in mediating positive and
      negative roles in B-cell activation and how these affect immune signaling and
      disease progression.

PMID- 15489918
TI  - Src in synaptic transmission and plasticity.
AB  - In the central nervous system (CNS), Src and other Src family kinases are widely
      expressed and are abundant in neurons. Src has been implicated in proliferation
      and differentiation during the development of the CNS. But Src is highly
      expressed in fully differentiated neurons in the developed CNS, implying
      additional functions of this kinase. Over the past decade, a large body of
      evidence has accumulated showing that a main function of Src is to upregulate the
      activity of N-methyl-D-aspartate (NMDA) receptors and other ion channels. NMDA
      receptors (NMDARs) are a principal subtype of glutamate receptors, which mediate
      fast excitatory transmission at most central synapses. In this review, we focus
      on Src as a regulator of NMDARs and on the role of Src in NMDAR-dependent
      synaptic plasticity. We also describe recent studies that give insights into the
      regulation of Src itself at glutamatergic synapses. By upregulating the function
      of NMDARs, Src gates the production of NMDAR-dependent synaptic potentiation and
      plasticity. Thus, Src may be critical for processes underlying physiological
      plasticity, including learning and memory, and pathological plasticity, such as
      pain and epilepsy.

PMID- 15489919
TI  - Role of STATs as downstream signal transducers in Src family kinase-mediated
      tumorigenesis.
AB  - The signal transducers and activators of transcription (STATs) were originally
      identified in the signaling pathway activated by the nontyrosine kinase
      containing cytokine receptors. The role of these STATs in hematopoietic cell
      signaling has been well described. In the case of cytokine receptors, activation
      of STAT tyrosine phosphorylation occurs through ligand-induced recruitment, and
      activation of the intracellular JAK kinases. However, STATs can also be activated
      by growth factor receptors, particularly the EGFR; as well as by members of the
      Src Family of Kinases (SFKs), particularly c-Src. In many cases, there is a
      differential activation of the STATs by these tyrosine kinases as compared to
      activation by the cytokine receptors. This difference provides for the potential
      of unique actions of STATs in response to growth factor receptor and SFK
      activation. Since there are many cancers in which SFKs and c-Src in particular,
      are co-overexpressed with growth factor receptors, it is not surprising that
      STATs play an important role in the tumorigenesis process induced by c-Src. The
      activation paradigm and role of STATs in these cancers, with particular emphasis
      on breast cancer models, is discussed.

PMID- 15489920
TI  - Molecular interdiction of Src-family kinase signaling in hematopoietic cells.
AB  - The ability of Src-family kinases (SFKs) to mediate signaling from cell surface
      receptors in hematopoietic cells is a function of their catalytic activity,
      location and binding partners. Kinase activity is regulated in the cell by
      kinases and phosphatases that alter the state of phosphorylation of key tyrosine
      residues and by protein binding partners that stabilize the kinase in active or
      inactive conformations or localize the enzyme to specific subcellular or
      submembrane domains. Kinase activity and function can be modulated experimentally
      through the use of small molecule inhibitors designed to directly target
      catalytic or binding domains or regulate the location of the protein by altering
      its state of acylation.

PMID- 15489921
TI  - [Immunoglobulin variable region gene rearrangement and hypermutation in
      paraneoplastic pemphigus associated Castleman's tumor].
AB  - OBJECTIVE: We have studied the role of lymphoproliferative tumors in the
      pathogenesis of autoimmune and the origin of the autoantibodies in paraneoplastic
      pemphigus (PNP) in recent years. A Castleman's tumor from a patient was
      identified to produce autoantibody. To identify the relationship between the
      tumor and pathogenesis of the disease, we analyzed the rearrangement of
      immunoglobulin variable region gene and its hypermutation in B cells of
      Castleman's tumor from a patient who was diagnosed of paraneoplastic pemphigus.
      METHODS: The surface markers of cultured tumor lymphocytes were assessed with
      immunochemistry staining. After total RNA of the tumor cells were isolated, the
      mRNA was reversely transcribed into cDNA. V(H) and V(L) genes were cloned and
      their sequences were analyzed. RESULTS: Immunochemistry staining and flow
      cytometer analysis showed that the tumor cells were CD20, HLA-DR, smIgM, and
      smIgG positive. The cloned IgV(H) and IGHV3-9*01 germ-line gene are homologous
      and so are the Ig V(L) and the IGKV4-1*01 germ-line gene. More nucleotide changes
      in the V(H) or V(L) occurred in CDRs than those in FRs. CONCLUSION: In this
      reported case, a clone of specific B-lymphocyte in the Castleman's tumor carrying
      functional rearranged immunoglobulin heavy and light chain genes was found to
      have experienced switch recombination and was possible to produce IgG
      autoantibody.

PMID- 15489922
TI  - [Detection and identification of Mycobacteria with polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) from patients with
      Mycobacterial skin infections].
AB  - OBJECTIVE: To establish a rapid approach to the detection and identification of
      Mycobacteria from lesions of patients with suspected Mycobacterial infections.
      METHODS: Specimens were obtained from five patients suspected to have
      Mycobacterial infections. DNA extracted from clinical samples was amplified by
      nested PCR. The PCR products were digested with HhaI, MboI, and BstUI restriction
      enzymes and applied to PAGE. The species of Mycobacteria were determined by
      restriction fragment length polymorphism (RFLP) analysis. Identification of
      Mycobacteria culture was also performed in 3 patients. RESULTS: M. marinum was
      found in two patients diagnosed as swimming pool granuloma. M. tuberculosis was
      found in one patient diagnosed as infectious skin granuloma. All these 3
      Mycobacteria were confirmed by Mycobacteria culture. A strain of M. tuberculosis
      and a strain of M. fortuitum were detected in remain two patients. CONCLUSION:
      The results above indicate that PCR-RFLP analysis is rapid and reliable in
      detection and identification of different Mycobacteria species from skin tissues.
      Application of this method will be helpful for early diagnosis and treatment of
      Mycobacteria skin infections.

PMID- 15489923
TI  - [DSRAD gene mutations in three families with dyschromatosis symmetrica
      hereditaria].
AB  - OBJECTIVE: To identify the DSRAD gene; mutations in three Chinese families with
      dyschromatosis symmetrica hereditaria. METHODS: All exons of DSRAD gene were
      analyzed in each person of these families with PCR-DNA sequencing. DNA samples
      from 100 unrelated, normally pigmented adult individuals were also included as
      control. RESULTS: We identified a missense mutation of C3220T (R1074C) in DSRAD
      gene in family A, and another missense mutation of G3325T (D1109Y) in DSRAD gene
      in family B and C. No same mutation was found in unaffected individuals in the
      families and the controls. CONCLUSION: We found two special missense mutations in
      DSRAD gene in three families of dyschromatosis symmetrica hereditaria. These
      mutations may impair DSRAD protein function, and as a consequence, cause skin
      dyschromatosis.

PMID- 15489924
TI  - [Retrospective analysis of 1905 patients with skin cancer from two general
      hospitals in western China from 1981 to 2000].
AB  - OBJECTIVE: To investigate the clinical features and changes in the incidence of
      skin cancer in two hospitals located in western China. METHODS: The patients
      diagnosed pathologically as skin cancer from 1981 to 2000 were retrospectively
      collected from the two hospitals. Clinical data of patients with skin cancer were
      collected and analyzed. RESULTS: (1) Of the 1 905 patients with skin cancer,
      squamous cell carcinoma accounted for 29.4%(560 patients), basal cell carcinoma
      28.0% (534), and cutaneous malignant melanoma(CMM) 16.0% (305). (2) There were
      591 patients with skin cancer diagnosed between 1980 and 1990, and 1 314 between
      1991 and 2000, and accounted for 0.34% and 0.58% of all biopsy cases,
      respectively. The number of total biopsy patients increased 1.6% every year
      during the 20 years. The number of biopsy patients with skin cancer and with CMM
      increased 3.5% and 3.9% every year,respectively. (3) Of the 305 CMM patients,
      63.3% located on the acra. These patients were elder, and have a higher rate of
      trauma and a higher incidence in the male than that in patients with CMM located
      on the other sites. (4) Of the 305 CMM patients, 64 (21%) had history of trauma
      at the primary onset sites, and 47 (15.4%) had history of small congenital nevi
      at the primary sites. CONCLUSION: There are some differences in the clinical
      features such as location and age between the skin cancer patients in our study
      and those in white population. The incidence of skin cancer in the two hospitals
      had been increasing in the 20 years (between 1981 and 2000). Both trauma and
      small congenital nevi are important risk factors of CMM.

PMID- 15489925
TI  - [Modulation of tropoelastin expression in cultured human dermal fibroblasts by
      heat shock].
AB  - OBJECTIVE: To observe the effect of heat shock on tropoelastin mRNA and protein
      expression in cultured human dermal fibroblasts and to elucidate the possible
      role of heat shock in the development of solar elastosis in human skin. METHODS:
      Primary cultured human dermal fibroblasts were incubated in 43 degrees C water
      bath for 30 minutes, then returned to 37 degrees C, 5%(volume fraction) CO(2)
      atmosphere normal culture condition. The cells were harvested at hour 24 and 48
      after heat treatment respectively. Total RNA was extracted from cell lysis and
      tropoelastin mRNA level was measured by Northern blot assay. Tropoelastin protein
      level in cultured supernatant was measured by Western blot assay. RESULTS: At
      hour 24 after heat treatment, the level of tropoelastin mRNA was enhanced to
      (163+/-12)% of control group (P<0.05). It was increased further to (221+/-22)% of
      control group at hour 48 after heat treatment (P<0.05). Similarly, the
      tropoelastin protein level was also increased to (149+/-12)% (P<0.05) at hour 24,
      and to (783+/-10)% (P<0.05) at hour 48 after heat shock as compared with control
      group. CONCLUSION: Heat shock could up-regulate tropoelastin mRNA and protein
      expression in primary cultured human dermal fibroblasts, and the over-expression
      of tropoelastin might play some roles in the development of solar elastosis in
      photoaged skin.

PMID- 15489926
TI  - [Cloning of the Aspergillus fumigatus squalene epoxidase gene].
AB  - OBJECTIVE: To clone Aspergillus fumigatus squalene epoxidase gene and to further
      investigate its role in terbinafine resistance. METHODS: The A.fumigatus genomic
      DNA library was transformed into pyrG-A. fumigatus strain protoplasts with
      polyethylene glycol-mediated transformation protocol. TRB-resistant pyrG+
      transformants were then isolated by being plated on MM-U with TRB (0.625 mg/L)
      plates. After confirmation of terbinafine-resistance by using both disk diffusion
      and NCCLS M38-A microdilution antifungal susceptibility testing, the gene
      conferring terbinafine-resistance was identified. Finally, the gene was cloned
      and retransformed into pyrG-A. fumigatus strain. RESULTS: From a total of 5x10(4)
      transformants, one TRB-resistant pyrG+ transformant was isolated, which showed
      the terbinafine-specific resistance without cross-resistance to any other
      antifungals. A. fumigatus squalene epoxidase gene was further identified to
      confer this terbinafine-resistance. As a result, the complete A. fumigatus
      squalene epoxidase gene was firstly cloned. Finally, the transformants with extra
      copies of A. fumigatus squalene epoxidase gene, again, showed the specific
      resistance to terbinafine. CONCLUSION: Extra copies of A. fumigatus squalene
      epoxidase gene, which was cloned for the first time in this study, could result
      in A. fumigatus resistance to terbinafine. This is a novel mechanism of
      terbinafine-resistance that needs further investigation for its clinical
      significance.

PMID- 15489927
TI  - [Effects of 1alpha,25-dihydroxyvitamin D(3) and UVB on cell proliferation and
      melanin synthesis of cultured human melanocyte].
AB  - OBJECTIVE: To study the effects of 1alpha,25-dihydroxyvitamin D(3) and UVB on
      cell proliferation and melanin synthesis of normal human melanocytes. METHODS:
      Melanocytes of foreskins of healthy men were cultured and treated with various
      concentration of 1alpha,25-dihydroxyvitamin D(3) or UVB (55 mJ/cm(2)),or both.
      Cell proliferation was measured with MTT assay .The synthesis of melanin was
      determined by chromatography. RESULTS: 1alpha,25-dihydroxyvitamin D(3) and UVB
      could promote the proliferation of cultured melanocyte,and 1alpha,25
      dihydroxyvitamin D(3) could promote the melanin synthesis. The significant
      concentration of 1alpha,25-dihydroxyvitamin D(3) ranging from 10(-7) to 10(-10)
      mol/L. CONCLUSION: 1alpha,25-dihydroxyvitamin D(3) and UVB irradiation could
      promote the proliferation of melanocyte,which indicates that they might be
      effective in the treatment of vitiligo.

PMID- 15489928
TI  - [Expression of nuclear factor kappaB and the effect of topical tacrolimus
      ointment on lesional atopic dermatitis skin].
AB  - OBJECTIVE: To investigate the role of nuclear factor kappaB (Rel/NF-kappaB) in
      pathogenesis of atopic dermatitis(AD) and the effect of topical 0.1%(mass
      fraction) or 0.03%(mass fraction) tacrolimus ointment on expression of NF-kappaB
      in lesional AD skin. METHODS: Immunohistochemistry has been employed to study the
      expression of NF-kappaB in normal skin and lesional AD skin before and after
      using topical tacrolimus ointment. RESULTS: The expressions of NF-kappaBp50 and
      NF-kappaBp65 were scattering or negative in normal keratinocytes. NF-kappaBp50
      was overexpressed on nuclear of basal and suprabasal keratinocytes in 9 cases of
      AD, NF-kappaBp65 was overexpressed in cytoplasm and perinuclear of basal and
      suprabasal keratinocytes. After using topical tacrolimus ointment for three weeks
      , nuclear NF-kappaBp50 expressed on basal and suprabasal keratinocytes were lost
      and NF-kappaBp50 was expressed sparsely on basal keratinocytes cytoplasm or
      nuclear. NF-kappaBp65 was expressed sparsely on basal and suprabasal
      keratinocytes cytoplasm. CONCLUSION: These data suggest that increased NF-kappaB
      activity may represent the basis of initiation or maintenance of the skin
      inflammatory response in atopic dermatitis. Topical tacrolimus may directly or
      indirectly inhibit NF-kappaB nuclear expression in keratinocytes and inhibit skin
      innate immuno-inflammatory response in atopic dermatitis that related to NF
      kappaB.

PMID- 15489929
TI  - [Eukaryotic expression and biological activities of anti-p185 erbB2 mouse/human
      chimeric antibody].
AB  - OBJECTIVE: Overexpression of the HER2/neu oncogene is a frequent molecular event
      in multiple human cancers. Being a cancer antigen, p185(erbB2) is an ideal target
      for immunotherapy. In order to decrease the immunogenicity of mouse anti
      p185(erbB2) monoclonal antibody in human cancer therapy, we constructed the
      eukaryotic expression vector of anti-p185(erbB2) chimeric monoclonal antibody and
      verified expression of the chimeric antibody in CHO-dhfr(-) cell. METHODS: The
      variable regions of light chain and heavy chain were amplified with RT-PCR and
      inserted into the chimeric antibody vector pWSD2. After CHO-dhfr(-) cells were
      transfected with recombination plasmid by lipofectAMINE, the chimeric antibody
      expressing level was identified with RT-PCR, indirect-ELISA, and Western blot.
      The specificity of the anti-p185(erbB2) chimeric antibody was testified with
      ELISA assay and immunoprecipitation. Moreover, the effects of chimeric antibody
      on the proliferation of breast cancer cell line SKBR3, which is overexpressing
      p185(erbB2), were measured with MTT assay in vitro. RESULTS: The anti-p185(erbB2)
      chimeric antibody eukaryotic expression vector was constructed successfully and
      the expression of the chimeric antibody in CHO-dhfr(-) was verified by RT-PCR,
      indirect-ELISA, and Western blot. ELISA assay showed that chimeric antibody
      reacted with cells overexpressing p185(erbB2) specifically, but did not react
      with that non-overexpressing p185(erbB2). Immunoprecipitation test confirmed that
      the chimeric antibody could bind to p185(erbB2) specifically. The MTT assay
      demonstrated that the chimeric antibody could inhibit the growth of SKBR3 cells
      overexpressing p185(erbB2) . CONCLUSION: The anti-p185(erbB2) mouse/human
      chimeric antibody that was expressed in CHO-dhfr(-) cells can bind to p185(erbB2)
      specifically and inhibit proliferation of SKBR3 cells overexpressing p185(erbB2)
      . It has a potential application in biotherapy of cancer.

PMID- 15489930
TI  - [Clinical features in 4 Chinese families with cerebral autosomal dominant
      arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)].
AB  - OBJECTIVE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leucoencephalopathy (CADASIL) is an inherited cerebral arteriolar disease in
      adulthood, which is caused by NOTCH3 gene mutation. The main symptoms were
      migraine, cerebral stroke, later with mood disorders and dementia in Caucasian
      patients. Recently, the disease was also recognized in Asian patients, in whom
      the migraine is rarely reported. In order to give the clinical features of
      Chinese patients, we described the clinical symptoms in 4 CADASIL families.
      METHODS: CADASIL was diagnosed by the investigation of ultra-structure changes of
      arteriole in sural nerve and NOTCH3 gene mutation in the 4 index cases. Detailed
      clinical and routine laboratory examinations were performed in these 4 patients,
      including electrocardiography, nerve conduction velocity, serum glycogen, and
      serum homocysteine. Additionally, we also collected the clinical data of the
      other 83 family members through interviews and the available medical records.
      RESULTS: Of the 83 persons, 29 were classified as clinical suspected patients,
      who presented one or more of the disease-related neurological symptoms, such as
      cerebral ischemic events and the cognitive impairment. All of them showed no
      common risk factors for stroke, such as diabetic mellitus, hypertension, and
      heart disease. The clinical suspected patients distributed in every consecutive
      generations and involved both sexes, which was according to the autosomal
      dominant inherited pattern. The onset age of the disease ranged from 28 to 70
      year-old and mainly between the 4th and the 5th decades. The main symptoms were
      recurrent episodic vertigo, with or without hemiplegia. At the same time or a
      little bit later, the cognitive impairment was developed in some patients.
      Compared with the typical presentations of the disease in European patients, none
      of our 29 patients showed migraine,one index case showed mild sensory disturbance
      in extremities. Elevated serum homocysteine level and abnormal of nerve
      conduction study in two index cases (3 and 4) were noticed. CONCLUSION: The onset
      age of the disease of our patients is similar to that of Caucasian patients. The
      main symptoms were stroke and dementia. Involvement of post circulation system
      was the main clinical feature for ischemic events in our patients. Dementia could
      be found in the early stage of disease. Migraine should not be regarded as a
      common clinical feature in our patients. The involvement of the peripheral nerves
      expanded the disease expression outside the central nervous system.

PMID- 15489931
TI  - [The distribution and clinical significance of IgG subclasses of anti-glomerular
      basement membrane antibodies].
AB  - OBJECTIVE: It was reported that major subclasses of anti-glomerular basement
      membrane (GBM) antibody were IgG1 and IgG4. The IgG1 subclass was mainly found in
      male patients and IgG4 subclass in female patients with anti-GBM disease. This
      study investigates the distribution of anti-GBM IgG subclasses and their
      association with clinical characteristics. METHODS: Sera from 50 patients
      diagnosed as anti-GBM disease during 1991-2003 were collected. The anti-GBM
      antibodies with IgG1, IgG2, IgG3, and IgG4 subclasses were detected with purified
      bovine alpha (IV) NC1 as solid phase ligand in ELISA. The association with
      clinical manifestations was further investigated. RESULTS: The positive rates of
      IgG anti-GBM subclasses were IgG1 94%, IgG2 56%, IgG3 12%, IgG4 88%,
      respectively. IgG1 and IgG4 were the main subclasses in anti-GBM IgG subclasses
      (P<0.01). The positive rates of the four subclasses had no significant difference
      between male and female, whereas the average positive percentage of IgG4 anti-GBM
      antibody was much higher in males than that in females (P<0.01). The average ages
      of patients with each subclass had no difference. The distribution of anti-GBM
      subclasses had no association with antineutrophil cytoplasmic antibody (ANCA),
      hematuria, proteinuria,or hemoptysis. The average positive percentage of IgG1 in
      patients with serum creatinine over 600 micromol/L was significantly higher than
      that in patients with serum creatinine less than 600 micromol/L (P<0.05), which
      suggested IgG1 might play an important role in the evolution and development of
      the disease. In the four patients with mild clinical presentations, three had
      IgG4 subclass, and only one patient who retained normal renal function in the
      follow-up exhibited pure IgG4 subclass. This suggested that IgG4 might not be
      inclined to cause severe damage. The average positive percentage of IgG4 subclass
      was higher in smoking patients than that in non-smoking patients (P<0.01).
      CONCLUSION: There is a restrictive distribution among the subclasses of anti-GBM
      antibody, in which IgG1 and IgG4 are the main subclasses. The distribution of
      anti-GBM IgG subclasses was not associated with gender.

PMID- 15489932
TI  - [A twin study of association of beta3AR Trp64Arg polymorphisms with insulin
      sensitivity].
AB  - OBJECTIVE: To investigate the influences of beta3 adrenergic receptor(beta3AR)
      Trp64Arg polymorphism on insulin resistance. METHODS: The insulin sensitivity was
      estimated with logarithm transformed homeostasis model assessment (HOMA). We
      enrolled 88 pairs of dizygotic twins for this study. We performed PCR-RFLP
      analysis to detect the Trp64Arg variants with BstO I digestion. RESULTS: The
      genotypic frequencies of Trp64Trp, Trp64Arg and Arg64Arg were 71.5%, 26.7% and
      1.7%. Those who carried Trp64Arg variant appeared to have lower insulin
      sensitivity compared to the one who didn't, but had no significance(P=0.145).
      Body mass index (BMI) had shown to be weakly positive correlated with lgHOMA. We
      found no significant association between the Trp64Arg variant and BMI.
      CONCLUSION: The presence of the Arg64 allele in beta3AR gene may predispose
      patients to insulin resistance, and further study with larger sample size may
      help to confirm the result.

PMID- 15489933
TI  - [The molecular interaction between P53 and telomeric repeat binding protein 1 in
      vitro].
AB  - OBJECTIVE: Cellular proliferate inhibition, senescence or apoptosis are induced
      by telomere shortening through the activation of P53 pathway, but so far, little
      is known of the mechanism. This study aimed to clarify the molecular regulation
      of P53 through telomere pathway by the investigation of molecular interaction
      between P53 and the main telomere associated protein telomeric repeat binding
      protein 1(TRBP1) in vitro. METHODS: Glutathione S-transferase (GST) alone and 4
      different human P53-GST fusion proteins were expressed in E.coli. and purified
      through glutathione Sepharose (TM)4B by affinity chromatography, P53s were wild
      type P53 (1-393), N terminal truncated form P53 2C (95-393), C terminal truncated
      form P53 N5 (2-293) and single amino acid mutant P53 R175H (175 arginine to
      histidine). Glutathione Sepharose (TM)4B, purified GST alone and P53 fusions were
      mixed with human breast cancer cell line MCF-7 cellular protein extracts through
      in vitro binding assay-pull down, the molecular interaction between P53 and TRBP1
      were detected by Western blot. RESULTS: SDS-PAGE and Coomassie brilliant blue
      staining showed that the molecular weights of all the purified proteins were as
      expected and purities were over 90%. Western blot of TRBP1 showed that both wild
      type P53 and P53 R175H could bind to TRBP1 of MCF-7 cells, and their binding
      capacities are similar, whereas GST alone and Glutathione Sepharose(TM) 4B beads
      could not. Compared with both of them, the interaction between P53 2C and TRBP1
      enhanced dramatically, but between P53 N5 and TRBP1 reduced significantly.
      CONCLUSION: P53 can interact with TRBP1 directly and in vitro, C terminus of P53
      (293-393) is the structural domain of their interaction. This C terminus domain
      dependent interaction between P53 and TRBP1 may be related to the cellular
      activities induced by telomere dynamic changing.

PMID- 15489934
TI  - [Identification of proteins interacting with androgen receptor- associated
      coregulator 267-alpha (ARA267-alpha) with the yeast two-hybrid system].
AB  - OBJECTIVE: To search for proteins interacting with ARA267-alpha with the yeast
      two-hybrid system in order to further investigate the function of ARA267-alpha.
      METHODS: We screened a pretransformed human brain cDNA library with the pGBKT7
      PHD-SET recombinant plasmid as a bait which express four PHD(plant homeodomain)
      and one SET[Su(var)3-9, Enhancer-of-zeste, Trithorax] conserved domains in ARA267
      alpha. The plasmids in positive yeast clones were selectively identified by
      restriction analysis and DNA sequencing. The interactions were retested by yeast
      two-hybrid assay. RESULTS: There were about six hundreds positive yeast clones on
      SD/-Ade/-His/-Leu/-Trp/2.5 mmol/L 3-AT/ X-alpha-Gal high-stringency selection
      plates. The pACT2-cDNA plasmids in sixty-five yeast clones were isolated and
      thirty-five cDNA inserts were sequenced. Sixteen different genes, including
      DR6(death receptor-6), PIAS3 (protein inhibitor of activated STAT3)and RanBPM(Ran
      binding protein in the microtubule-organizing center), were identified after
      BLAST in GenBank. The yeast two-hybrid retest showed that all but RanBPM were
      true interactors of ARA267-alpha-PHD-SET. CONCLUSION: The ARA267-alpha-PHD-SET
      can interact with several distinct proteins. This suggests that ARA267-alpha is a
      protein having multiple functions. RanBPM might be a transcriptional factor.

PMID- 15489935
TI  - [Side effects of glucocorticosteroids in the management of 1291 patients of
      SARS].
AB  - OBJECTIVE: To analysis the relationship between glucocorticosteroids (GCS) usage
      and side effects in the treatment of severe acute respiratory syndrome (SARS).
      METHODS: All clinical records of probable SARS patients in Beijing were collected
      and input into an Epi6 database, in which 1 291 patients had entire information
      and met the clinical criteria of SARS. The usage of GCS and GCS associated side
      effects were analyzed retrospectively. RESULTS: Patients accepted GCS therapy
      were 83.96% (n=1 084), whereas 16.04%(n=207) did not take GCS. The average dosage
      of GCS was 160 mg/d in the first week, and then reduced to 80 mg/d and 40 mg/d in
      the second and the third weeks, respectively. Initial blood glucose, systolic
      pressure (SBP), and diastolic pressure (DBP) were no significant difference
      between GCS group and non-GCS group. The highest blood glucose during the
      treatment in GCS group was markedly higher than that in non-GCS group [(8.68+/
      4.80) mmol/L vs (6.39+/-3.71) mmol/L, P<0.05)]. The highest blood glucose and
      average blood glucose after initiation of GCS therapy were elevated in GCS group.
      The levels of blood glucose were correlated with the initial, maximum, and
      cumulative GCS dosages. Average blood glucose was increased markedly in groups
      with MP(Initial) > or =80 mg/d (Methyprednisonlone), MP(Maximal) > or =160 mg/d,
      or MP(Cumulative) > or = 3000 mg. The blood glucose grew up significantly in the
      first and the second weeks in the treatment with GCS, and then returned to normal
      level gradually. Hyperglycemia duration in the group with MP(Cumulative) > or
      =3000 mg persisted longer than that in the other groups (P< 0.05). The lowest
      serum potassium during the treatment and the duration of hypokalemia in GCS group
      were significantly different from that in non-GCS group [(3.66+/-0.50) mmol/L vs
      (4.01+/-0.51) mmol/L, P< 0.001 ;1(1, 75) days vs 1(1, 9) days, P<0.05,
      respectively]. Average serum potassium and the duration of hypokalemia were
      related to the dosages of GCS. Serum potassium reached its nadir in the first
      week of GCS treatment and then grew up in the second week. In groups with
      MP(Initial) > or =320 mg/d, MP(Maximal) > or =320 mg/d, and MP(Cumulative) > or
      =3000 mg, the level of serum potassium was lower and the duration of hypokalemia
      was longer than that in other groups. They began to returned to normal level in
      the third week. Administration of GCS prolonged the time of hypocalcemia[19 (1,
      74) days in GCS group vs 8 (1, 32) days in non-GCS group, P< 0.05]. The duration
      of hypocalcemia was prolonged according to the increasing of the maximal or the
      cumulative dosage of GCS. However, the duration of hypocalcemia in group with
      MP(Cumulative) <999 mg was similar to that in non-GCS group (P > 0.05). After GCS
      administration, SBP and DBP were increased gradually, and reached their peaks in
      the fourth week [SBP(117.2+/-14.0) mm Hg and DBP (72.5+/-9.1) mm Hg vs SBP
      (120.0+/-12.5) mm Hg and DBP (74.5+/-8.7) mm Hg, P< 0.05, 1 mm Hg=0.133 kPa].
      CONCLUSION: Hyperglycemia and hypokalemia are correlated with GCS dosage and
      duration. Administration with GCS influences SBP, DBP, and duration of
      hypocalcemia. Appropriate low dosage of GCS (MP(Initial) and MP(Maximal) < 159
      mg/d, MP(Cumulative)< 2999 mg) causes few changes of blood glucose, serum
      potassium, and blood calcium. It is important to monitor laboratory findings
      during the treatment with GCS.

PMID- 15489936
TI  - [The killing effect of cytotoxic T lymphocytes on esophageal adenocarcinoma cells
      mediated by gp96-peptide complexes].
AB  - OBJECTIVE: To study the immunotherapeutic effect on the esophageal adenocarcinoma
      mediated by gp96-peptide complexes isolated from the same kind of tumor. METHODS:
      gp96-peptide complexes were purified from nude mice tumors burdened by
      subcutaneous injection of human esophageal adenocarcinoma cell line SEG-1. gp96
      peptide complexes were carried by the dendritic cells(DC) induced from human
      peripheral blood mononuclear cells to prepare gp96-DC vaccine. The proliferation
      of lymphocytes was tested with trypan-blue stain. The quantity of interferon
      gamma(IFN-gamma) released from cytotoxic T lymphocytes (CTL) was detected with
      ELISA method. The killing effect of CTL on target cell SEG-1 was measured with
      MTT. RESULTS: We obtained 120 microg gp96 from 55 g tumor tissue. DC, gp96, and
      gp96-DC all could elicit the proliferation of lymphocytes and make them becoming
      into CTL which released IFN-gamma and showed different degrees of killing effect
      on target cell SEG-1. gp96-DC has the strongest eliciting effect among them. At
      the ratio of E(effect) to T(target) as 40:1,the killing rate was 68%. No
      significant difference between the effects of CTL induced by DC alone and of
      lymphocytes without specific antigen on SEG-1 and K562 cells. CONCLUSION: The
      gp96-peptide complexes from tumors can improve the effect of eliciting lymphocyte
      proliferation of DC and make the lymphocyte becoming into CTL more effectively.
      These CTLs show prominent killing effect on the target tumor cells.

PMID- 15489937
TI  - [Incidence of deep venous thrombosis (DVT) in patients undergoing thoracotomy and
      changes of hemostasis].
AB  - OBJECTIVE: To survey the incidence of deep venous thrombosis (DVT) in high risk
      patients undergoing thoracotomy and observe the changes of hemostatic activity.
      METHODS: Fifty-two consecutive patients (ages that ranged from 35 to 79, 34 men
      and 18 women) with lung or esophagus cancer were enrolled into this prospective
      trial. The patients included underwent major thoracic surgery from February 2003
      to April 2003. Bilateral lower extremity duplex ultrasonography for DVT screening
      was performed 3-10 days post surgery in all 52 patients and 57 matched clinic
      normal controls. Venous blood was collected to determine fibrinogen (FIB), D
      dimer(D-D), plasminogen activator inhibitor (PAI), antithrombin (AT)i thrombin
      antithrombin complex (TAT), prothrombin time (PT), international normalized ratio
      (INR), and activated partial thromboplastin time (APTT) immediately before
      surgery, the third and tenth days postoperatively. No patient had a prior
      thromboembotic history. Risk factors for DVT were evaluated. RESULTS: Of the 52
      patients, 28 (53.8%) had an acute postoperative DVT detected in the calf. One
      patient died of suspected pulmonary embolism postoperatively. Plasma levels of
      FIB and D-D increased significantly up to 7 d after operation. AT level decreased
      significantly 3 d after operation and returned to normal 7 d latter. TAT
      increased significantly 3 d post operation and decreased to normal on day 7. PAI
      level was lowered 3 d after surgery, but increased significantly on day 7
      compared with that on day 3. With the addition of risk factors related to
      thrombosis, the incidence of DVT was increased correspondingly. CONCLUSION: Of
      the patients undergoing major thoracic surgery,53.8% of them had a postoperative
      DVT by postoperative screening duplex ultrasound. In Chinese population,
      incidence of DVT appears to be high without prophylaxis, which is similar to
      other reports of westerners. These patients had a number of risk factors for the
      development of DVT, which include older age, overweight, hypertension, diabetes,
      and history of thromboembolism, etc. Prophylactic measures should be taken
      against postoperative venous thromboembolism in major thoracic surgery with high
      risk, including early mobilization, anticoagulant therapy with heparins, and
      intermittent pneumatic compression (IPC).

PMID- 15489938
TI  - [Assessment of total body water of patients on hemodialysis with urea kinetic
      model].
AB  - OBJECTIVE: To propose a method to evaluate the total body water (TBW) of patients
      on hemodialysis with urea kinetic model (UKM), and compare it with body surface
      bio-impedance spectrum (BIS) analysis. METHODS: We enrolled 24 adult patients
      with end stage renal disease (ESRD) without hyper-catabolism in our dialysis
      center. All of them had been on hemodialysis for more than 3 months. TBW was
      measured with BIS analysis immediately before and after dialysis session, and one
      hour after hemodialysis session. Spent dialysate was collected; blood samples
      were taken before and one hour after hemodialysis session, TBW before
      hemodialysis session were calculated by UKM. RESULTS: Patients were 6 men and 18
      women, the average age was (51.2+/-13.5) years and the average time on dialysis
      was (33.2+/-36.7) months. Causes of ESRD included chronic glomerulonephritis (8
      patients), diabetic nephropathy (1 patients), hypertensive renal damage (1
      patients), interstitial nephritis(two patients), chronic pyelonephritis (two
      patients). The average ultrafiltration volume was (2.7+/-1.0) L (0.5-4.4 L) .
      Plasma urea concentrations were (23.06+/-5.76) mmol/L and (8.15+/-2.06) mmol/L
      before and one hour after hemodialysis session, respectively. There was no
      significant difference between TBW measured immediately after and one hour after
      hemodialysis session with BIS analysis [(29.9+/-8.8) L and (29.8+/-8.6) L,
      respectively; average difference was (0.1+/-0.9)L, P=0.70]. These two
      measurements correlated very well (Pearson r=0.99, P<0.05). There was no
      significant difference between UKM and BIS analysis [(31.4+/-7.3) L and (31.3+/
      8.6) L, respectively; average difference was (0.2+/-4.5) L, P=0.87]. Results of
      these two methods correlated very well (Pearson r=0.86, r(2)=0.73,P< 0.05).
      CONCLUSION: TBW measured with UKM in patients on hemodialysis provides theoretic
      basis for fluid status evaluation and dry body weight assessment.

PMID- 15489939
TI  - [Application of molecular biology techniques in the identification of pathogenic
      fungi and the diagnosis of fungal infection].
AB  - With the increasing incidence and mortality of fungal infection, the requirements
      for strict diagnostic approaches became a very urgent issue. Because of the
      traditional detective techniques, such as culture, gave poor diagnostic outcomes,
      the molecular biological techniques are expected to develop the potential
      diagnostic approaches. During the past decades, we have carried out serial
      studies on the molecular properties of pathogenic fungi, and we would like to
      review as following. Firstly, we applied several molecular tools in
      classification and identification of pathogenic fungi. We performed random
      amplification of polymorphic DNA (RAPD), restriction fragment length polymorphism
      (RFLP) and other techniques in studying the typing, to classify and identify the
      properties of Dermatophytes, Candida spp., Cryptococcus neoformans, Dematiaceous
      fungi, and Aspergillus spp. Interestingly, we found the same T. rubrum strain
      might infect different sites of the host, while a site-specificity displayed in
      T. mentagrophytes. This finding indicated the genetic discrepancies among the
      fungi. Beside, we also found that the E. dermatitis strains with different
      virulences possessed some discrepancies at gene level. We then developed a PCR
      based molecular procedure to identify the novel species in Exophiala spp. As the
      applicable strategy, we also investigated the rDNA sequence properties in several
      fungi. And as a result, we submitted for the first time to GenBank the complete
      sequence of Aspergillus fumigatus rDNA/ITSI/ITSII, which provided the basis for
      designing the species-specific probes and for its further clinical applications.
      Secondly, we have tried to develop the molecular diagnostic approaches based on
      our DNA sequence data which were used for identification studies previously. By
      analyzing the DNA sequence of Aspergillus fumigatus rDNA/ITSI/ITSII, we developed
      a nested PCR method to detect Aspergillus fumigatus genes. Our preliminary
      results indicated that this PCR-based molecular approach has great importance in
      the diagnosis of invasive aspergillosis. We also designed the species-specific
      probes and then established several in situ hybridization procedures. We found
      these hybridization methods could get the positive rate up to 81% (13/16), which
      suggests that these methods have potential diagnostic value for invasive
      candidiasis and aspergillosis. Based on our experiences, we would conclude that
      the molecular biological techniques possess great value to investigate the
      biological properties of pathogenic fungi, and we are looking forward to see more
      and more molecular tools will be used in the pathogenic mechanisms of fungal
      infections and antifungal activity studies.

PMID- 15489940
TI  - [The new development on pathogenesis of autoimmune paraneoplastic pemphigus].
AB  - Paraneoplastic pemphigus (PNP) is an autoimmune mucocutaneous disease first named
      by Anhalt, et al in 1990. The disease is characterized by such distinctive
      clinical symptoms and signs as severe, painful mucosal erosions, polymorphous
      skin lesions, histopathology hallmarks, and immunological findings. The situation
      typically presents in patients with lymphoproliferative diseases and primarily
      malignancies. A main challenge of the study is the relationship between the
      existence of associated tumors and the autoimmune reaction to the skin. Some
      researchers suspected that the possible expression of foreign antigens on the
      tumor can cross react with epidermal antigens inducing the auto-reactive clones
      of T-lymphocytes. Some speculated that the type of tumors associated with PNP may
      produce plakin proteins that result in initiation of the immune response. Other
      reports believed the autoimmune reaction is related to the epitope spreading or
      to the changing of cytokines. We analyzed 12 PNP patients diagnosed in our
      department in the past few years. An intensive study to the B cells in the PNP
      associated with tumors demonstrated that the tumors have structural basis to
      produce antibody. The similar immunoglobulin heavy chain genes of tumor B cells
      in 7 patients strongly suggested that the B cell clones were functional and
      recognized the same antigen epitope. The autoantibodies secreted by the tumor can
      react against specific plakin proteins in epidermis, lead to the impairment of
      cell-cell adhesion, and cause the mucocutaneous lesions. The clinical
      significance of the RESULTS indicates the importances of early finding and total
      resection of the associated tumors, and the usage of IVIG pre or during operation
      to prevent Bronchitis Obliterans. The new finding is also important for the study
      of other antibody mediated autoimmune diseases.

PMID- 15489941
TI  - [Research advances of genodermatosis in China].
AB  - Research in the field of genetic skin disease has grown rapidly over the past two
      decades. Even though the fundamental molecular pathways are still not fully
      understood, there have prominent advances in our understanding of the underlying
      mechanisms involved in the pathogenesis of genodermatosis. Dermatologists in
      China contributed to this field in recent years. They found the causative genes
      involved in primary erythermalgia and familial trichoepithelioma. Different gene
      mutations involved in more than twenty kinds of genodermatosises have been
      detected. This review will synthesize recent findings of the genodermatosises in
      China.

PMID- 15489942
TI  - Group science.

PMID- 15489943
TI  - Reflecting on 80 years of excellence.
AB  - A small group of members of the American Society for Clinical Investigation began
      chatting in 1916 about the possibility of launching a new biomedical research
      journal. By October 1924, they managed to make the idea a reality with the
      publication of the first issue of the Journal of Clinical Investigation. Our 80th
      birthday seems an appropriate time to reflect on the history of biomedical
      science as it has been played out on our pages.

PMID- 15489944
TI  - Blasts from the past.
AB  - With this issue of the JCI, we celebrate the 80th anniversary of the Journal.
      While 80 years is not a century, we still feel it is important to honor what the
      JCI has meant to the biomedical research community for 8 decades. To illustrate
      why the JCI is the leading general-interest translational research journal edited
      by and for biomedical researchers, we have asked former JCI editors-in-chief to
      reflect on some of the major scientific advances reported in the pages of the
      Journal during their tenures.

PMID- 15489945
TI  - Richard Havel, Howard Eder, and the evolution of lipoprotein analysis.
AB  - In 1956, the JCI published a paper by Richard Havel, Howard Eder, and Joseph
      Bragdon on a method using an ultracentrifuge to physically separate plasma
      lipoproteins and chemical methods to analyze their lipid constituents. This paper
      has been much cited (7081 times as of this writing) in part because it represents
      a solid method that, with various modifications, has been applicable for the
      study of lipoproteins for almost half a century.

PMID- 15489946
TI  - Endothelial cell culture: beginnings of modern vascular biology.
AB  - Endothelial cells derived from human umbilical veins were first successfully
      cultured in vitro in 1973. Weibel-Palade bodies and the von Willebrand factor
      antigen were used as morphological, immunohistochemical, and functional markers
      to unequivocally identify the cells. These landmark studies helped initiate the
      growth of modern vascular biology.

PMID- 15489947
TI  - One thing leads to another.
AB  - In 1956, the JCI published an article by Vincent Dole on a method for titrating
      plasma fatty acids that uncovered the importance of fatty acids as a substrate
      for glucose metabolism. When asked to prepare a historical perspective on this
      very popular paper, I paid Dole a visit and we reminisced. His answer to my
      question of how he came to do this work on plasma fatty acids was: "Well, one
      thing leads to another." Let me remind the reader of what "things" were like in
      1956 and how they might have related to Dole's important contribution.

PMID- 15489948
TI  - The birth of clinical body plethysmography: it was a good week.
AB  - Nearly fifty years ago, Arthur B. DuBois, Julius H. Comroe Jr., and their
      colleagues published two papers on the use of body plethysmography to measure
      lung volume and airway resistance. These two articles in the JCI are almost the
      most-cited doublet in the Journal's entire archive. Remarkably, the methods
      described then are still in use today in clinical pulmonary function
      laboratories. Though body plethysmography had been used before, there were
      serious technical problems; it was extraordinary that DuBois managed to solve
      most of these in one week. Times have changed and molecular medicine now
      dominates the JCI, but these articles remind us that biomedical research goes
      beyond the molecular.

PMID- 15489949
TI  - Quantifying cerebral blood flow: regional regulation with global implications.
AB  - In 1948, Seymour S. Kety and Carl F. Schmidt published back-to-back papers in the
      JCI that are widely acknowledged as landmarks. Upon publication, the studies
      resolved a century-old debate, irrefutably demonstrating that cerebral blood flow
      is regionally regulated. The reported findings turned out to be so powerful in
      their implications that they provided the inspirational spark that illuminated a
      brand-new field: functional brain imaging. Thus these papers are landmarks of the
      rarest kind, not only ending a controversy, but also giving birth to one of the
      most exciting fields within modern day neuroscience.

PMID- 15489950
TI  - The legacy of Homer W. Smith: mechanistic insights into renal physiology.
AB  - In 1945, Homer W. Smith published an article in the JCI that clearly demonstrated
      that para-aminohippuric acid is the most suitable agent for the evaluation of
      renal plasma flow in both humans and dogs; in addition, the paper provided
      detailed methodology that is still in use today. This paper is but one of many
      outstanding works performed by Smith and his colleagues that clearly established
      the clearance technique as a powerful noninvasive approach to gain mechanistic
      insights into intrarenal function.

PMID- 15489951
TI  - Berson, Yalow, and the JCI: the agony and the ecstasy.
AB  - The isolation of insulin in 1921 by Banting, Best, Collip, and Macleod stands as
      one of the most dramatic stories in modern medical investigation. Only two years
      passed between the initial experiments in dogs to widespread human application to
      the awarding of the Nobel Prize in 1923. Insulin-related research has also served
      as a focus, at least in part, for the work of three other Nobel Prize recipients:
      determination of the chemical structure of insulin by Frederick Sanger in 1958;
      determination of the three-dimensional structures of insulin and vitamin B12 by
      Dorothy Hodgkin in 1964; and finally, the development of immunoassay by Solomon
      Berson and Rosalyn Yalow in 1959-1960, which led to a Nobel Prize for Yalow in
      1977 (five years after the untimely death of Berson). The history of Yalow and
      Berson's discovery and its impact on the field is an illustration of the adage
      that every story has two sides.

PMID- 15489952
TI  - Superoxide production by phagocytic leukocytes: the scientific legacy of Bernard
      Babior.
AB  - It was 32 years ago that Bernard Babior, Ruby Kipnes, and I submitted a paper to
      the JCI reporting that polymorphonuclear leukocytes produce superoxide (O(2) (-))
      during phagocytosis and that this highly reactive oxygen radical might function
      as a microbicidal agent. The story of how our lab came to this discovery is one
      of a special relationship between a student and his brilliant mentor.

PMID- 15489953
TI  - Atrogin-1/muscle atrophy F-box inhibits calcineurin-dependent cardiac hypertrophy
      by participating in an SCF ubiquitin ligase complex.
AB  - Calcineurin, which binds to the Z-disc in cardiomyocytes via alpha-actinin,
      promotes cardiac hypertrophy in response to numerous pathologic stimuli. However,
      the endogenous mechanisms regulating calcineurin activity in cardiac muscle are
      not well understood. We demonstrate that a muscle-specific F-box protein called
      atrogin-1, or muscle atrophy F-box, directly interacts with calcineurin A and
      alpha-actinin-2 at the Z-disc of cardiomyocytes. Atrogin-1 associates with Skp1,
      Cul1, and Roc1 to assemble an SCF(atrogin-1) complex with ubiquitin ligase
      activity. Expression of atrogin-1 decreases levels of calcineurin A and promotes
      its ubiquitination. Moreover, atrogin-1 attenuates agonist-induced calcineurin
      activity and represses calcineurin-dependent transactivation and NFATc4
      translocation. Conversely, downregulation of atrogin-1 using adenoviral small
      interfering RNA (siRNA) expression enhances agonist-induced calcineurin activity
      and cardiomyocyte hypertrophy. Consistent with these cellular observations,
      overexpression of atrogin-1 in hearts of transgenic mice reduces calcineurin
      protein levels and blunts cardiac hypertrophy after banding of the thoracic
      aorta. These studies indicate that the SCF(atrogin-1) ubiquitin ligase complex
      interacts with and represses calcineurin by targeting calcineurin for ubiquitin
      mediated proteolysis, leading to inhibition of cardiac hypertrophy in response to
      pathologic stimuli.

PMID- 15489954
TI  - Noncleavable poly(ADP-ribose) polymerase-1 regulates the inflammation response in
      mice.
AB  - Poly(ADP-ribosyl)ation is rapidly formed in cells following DNA damage and is
      regulated by poly(ADP-ribose) polymerase-1 (PARP-1). PARP-1 is known to be
      involved in various cellular processes, such as DNA repair, genomic stability,
      transcription, and cell death. During apoptosis, PARP-1 is cleaved by caspases to
      generate 89-kDa and 24-kDa fragments, a hallmark of apoptosis. This cleavage is
      thought to be a regulatory event for cellular death. In order to understand the
      biological significance of PARP-1 cleavage, we generated a PARP-1 knockin (PARP
      1(KI/KI)) mouse model, in which the caspase cleavage site of PARP-1, DEVD(214),
      was mutated to render the protein resistant to caspases during apoptosis. While
      PARP-1(KI/KI) mice developed normally, they were highly resistant to endotoxic
      shock and to intestinal and renal ischemia-reperfusions, which were associated
      with reduced inflammatory responses in the target tissues and cells due to the
      compromised production of specific inflammatory mediators. Despite normal binding
      of NF-kappaB to DNA, NF-kappaB-mediated transcription activity was impaired in
      the presence of caspase-resistant PARP-1. This study provides a novel insight
      into the function of PARP-1 in inflammation and ischemia-related
      pathophysiologies.

PMID- 15489955
TI  - Requirement for sphingosine 1-phosphate receptor-1 in tumor angiogenesis
      demonstrated by in vivo RNA interference.
AB  - Angiogenesis, or new blood vessel formation, is critical for the growth and
      spread of tumors. Multiple phases of this process, namely, migration,
      proliferation, morphogenesis, and vascular stabilization, are needed for optimal
      tumor growth beyond a diffusion-limited size. The sphingosine 1-phosphate (S1P)
      receptor-1 (S1P(1)) is required for stabilization of nascent blood vessels during
      embryonic development. Here we show that S1P(1) expression is strongly induced in
      tumor vessels. We developed a multiplex RNA interference technique to
      downregulate S1P(1) in mice. The small interfering RNA (siRNA) for S1P(1)
      specifically silenced the cognate transcript in endothelial cells and inhibited
      endothelial cell migration in vitro and the growth of neovessels into
      subcutaneous implants of Matrigel in vivo. Local injection of S1P(1) siRNA, but
      not a negative control siRNA, into established tumors inhibited the expression of
      S1P(1) polypeptide on neovessels while concomitantly suppressing vascular
      stabilization and angiogenesis, which resulted in dramatic suppression of tumor
      growth in vivo. These data suggest that S1P(1) is a critical component of the
      tumor angiogenic response and argue for the utility of siRNA technology in
      antiangiogenic therapeutics.

PMID- 15489956
TI  - A new model for dermatitis herpetiformis that uses HLA-DQ8 transgenic NOD mice.
AB  - Dermatitis herpetiformis (DH) is an autoimmune blistering skin disorder that is
      associated with gluten sensitivity. It presents as a papulovesicular rash and is
      often associated with enteropathy. The rash resolves when the patient is placed
      on a gluten-free diet and/or dapsone. DH, as well as celiac disease, is tightly
      associated with DQ2 and DQ8. A novel mouse model for DH is described that
      utilizes the NOD background and the HLA-DQ8 transgene. The addition of DQ8
      contributes sensitivity to gliadin, and the addition of the NOD background
      contributes to autoimmunity and pathogenesis. Fifteen NOD DQ8+ mice of 90 that
      were sensitized to gluten developed blistering pathology similar to that seen in
      DH. Neutrophil infiltration of the dermis, deposition of IgA at the dermal
      epidermal junction, and a complete reversal of the blistering phenomenon with the
      administration of a gluten-free diet with or without dapsone were observed. None
      of the 3 blistering mice examined had small-bowel pathology. This animal model of
      DH will be useful to determine the specificity of the IgA deposits, as well as
      the pathogenic mechanisms that occur in the skin as a result of gluten ingestion.

PMID- 15489957
TI  - Epithelial hypoxia-inducible factor-1 is protective in murine experimental
      colitis.
AB  - Mucosal epithelial cells are uniquely equipped to maintain barrier function even
      under adverse conditions. Previous studies have implicated hypoxia in mucosal
      tissue damage resulting from both acute and chronic inflammation. Given the
      importance of the transcriptional regulator hypoxia-inducible factor-1 (HIF-1)
      for adaptive hypoxia responses, we hypothesized that HIF-1 may serve as a barrier
      protective element during mucosal inflammation. Initial studies of hapten-based
      murine colitis revealed extensive mucosal hypoxia and concomitant HIF-1
      activation during colitis. To study this in more detail, we generated 2 mouse
      lines with intestinal epithelium-targeted expression of either mutant Hif1a
      (inability to form HIF-1) or mutant von Hippel-Lindau gene (Vhlh; constitutively
      active HIF-1). Studies of colitis in these mice revealed that decreased HIF-1
      expression correlated with more severe clinical symptoms (mortality, weight loss,
      colon length), while increased HIF levels were protective in these parameters.
      Furthermore, colons with constitutive activation of HIF displayed increased
      expression levels of HIF-1-regulated barrier-protective genes (multidrug
      resistance gene-1, intestinal trefoil factor, CD73), resulting in attenuated loss
      of barrier during colitis in vivo. Taken together, these studies provide insight
      into tissue microenvironmental changes during model inflammatory bowel disease
      and identify HIF-1 as a critical factor for barrier protection during mucosal
      insult.

PMID- 15489958
TI  - Human mitochondrial peptide deformylase, a new anticancer target of actinonin
      based antibiotics.
AB  - Peptide deformylase activity was thought to be limited to ribosomal protein
      synthesis in prokaryotes, where new peptides are initiated with an N-formylated
      methionine. We describe here a new human peptide deformylase (Homo sapiens PDF,
      or HsPDF) that is localized to the mitochondria. HsPDF is capable of removing
      formyl groups from N-terminal methionines of newly synthesized mitochondrial
      proteins, an activity previously not thought to be necessary in mammalian cells.
      We show that actinonin, a peptidomimetic antibiotic that inhibits HsPDF, also
      inhibits the proliferation of 16 human cancer cell lines. We designed and
      synthesized 33 chemical analogs of actinonin; all of the molecules with potent
      activity against HsPDF also inhibited tumor cell growth, and vice versa,
      confirming target specificity. Small interfering RNA inhibition of HsPDF protein
      expression was also antiproliferative. Actinonin treatment of cells led to a
      tumor-specific mitochondrial membrane depolarization and ATP depletion in a time-
      and dose-dependent manner; removal of actinonin led to a recovery of the membrane
      potential consistent with indirect effects on the electron transport chain. In
      animal models, oral or parenteral actinonin was well tolerated and inhibited
      human prostate cancer and lung cancer growth. We conclude that HsPDF is a new
      human mitochondrial enzyme that may provide a novel selective target for
      anticancer therapy by use of actinonin-based antibiotics.

PMID- 15489959
TI  - Mitochondrial survivin inhibits apoptosis and promotes tumorigenesis.
AB  - Evasion of apoptosis is a hallmark of cancer, but the molecular circuitries of
      this process are not understood. Here we show that survivin, a member of the
      inhibitor of apoptosis gene family that is overexpressed in cancer, exists in a
      novel mitochondrial pool in tumor cells. In response to cell death stimulation,
      mitochondrial survivin is rapidly discharged in the cytosol, where it prevents
      caspase activation and inhibits apoptosis. Selective targeting of survivin to
      mitochondria enhances colony formation in soft agar, accelerates tumor growth in
      immunocompromised animals, and abolishes tumor cell apoptosis in vivo. Therefore,
      mitochondrial survivin orchestrates a novel pathway of apoptosis inhibition,
      which contributes to tumor progression.

PMID- 15489960
TI  - Inhibition of diabetic nephropathy by a decoy peptide corresponding to the
      "handle" region for nonproteolytic activation of prorenin.
AB  - We found that when a site-specific binding protein interacts with the "handle"
      region of the prorenin prosegment, the prorenin molecule undergoes a
      conformational change to its enzymatically active state. This nonproteolytic
      activation is completely blocked by a decoy peptide with the handle region
      structure, which competitively binds to such a binding protein. Given increased
      plasma prorenin in diabetes, we examined the hypothesis that the nonproteolytic
      activation of prorenin plays a significant role in diabetic organ damage.
      Streptozotocin-induced diabetic rats were treated with subcutaneous
      administration of handle region peptide. Metabolic and renal histological changes
      and the renin-Ang system components in the plasma and kidneys were determined at
      8, 16, and 24 weeks following streptozotocin treatment. Kidneys of diabetic rats
      contained increased Ang I and II without any changes in renin, Ang-converting
      enzyme, or angiotensinogen synthesis. Treatment with the handle region peptide
      decreased the renal content of Ang I and II, however, and completely inhibited
      the development of diabetic nephropathy without affecting hyperglycemia. We
      propose that the nonproteolytic activation of prorenin may be a significant
      mechanism of diabetic nephropathy. The mechanism and substances causing
      nonproteolytic activation of prorenin may serve as important therapeutic targets
      for the prevention of diabetic organ damage.

PMID- 15489961
TI  - Effect of fetal hemoglobin on microvascular regulation in sickle transgenic
      knockout mice.
AB  - In sickle cell disease, intravascular sickling and attendant flow abnormalities
      underlie the chronic inflammation and vascular endothelial abnormalities.
      However, the relationship between sickling and vascular tone is not well
      understood. We hypothesized that sickling-induced vaso-occlusive events and
      attendant oxidative stress will affect microvascular regulatory mechanisms. In
      the present studies, we have examined whether microvascular abnormalities
      expressed in sickle transgenic-knockout Berkeley (BERK) mice (which express
      exclusively human alpha- and beta(S)-globins with <1% gamma-globin levels) are
      amenable to correction with increased levels of antisickling fetal hemoglobin
      (HbF). In BERK mice, sickling, increased oxidative stress, and hemolytic anemia
      are accompanied by vasodilation, compensatory increases in eNOS and COX-2, and
      attenuated vascular responses to NO-mediated vasoactive stimuli and
      norepinephrine. The hypotension and vasodilation (required for adequate oxygen
      delivery in the face of chronic anemia) are mediated by non-NO vasodilators
      (i.e., prostacyclin) as evidenced by induction of COX-2. In BERK mice, the
      resistance to NO-mediated vasodilators is associated with increased oxidative
      stress and hemolytic rate, and in BERK + gamma mice (expressing 20% HbF), an
      improved response to these stimuli is associated with reduced oxidative stress
      and hemolytic rate. Furthermore, BERK + gamma mice show normalization of vessel
      diameters, and eNOS and COX-2 expression. These results demonstrate a strong
      relationship between sickling and microvascular function in sickle cell disease.

PMID- 15489962
TI  - Epigenetic regulation of 11 beta-hydroxysteroid dehydrogenase type 2 expression.
AB  - The enzyme 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta HSD2) is
      selectively expressed in aldosterone target tissues, where it confers aldosterone
      selectivity for the mineralocorticoid receptor by inactivating 11 beta
      hydroxyglucocorticoids. Variable activity of 11 beta HSD2 is relevant for blood
      pressure control and hypertension. The present investigation aimed to elucidate
      whether an epigenetic mechanism, DNA methylation, accounts for the rigorous
      control of expression of the gene encoding 11 beta HSD2, HSD11B2. CpG islands
      covering the promoter and exon 1 of HSD11B2 were found to be densely methylated
      in tissues and cell lines with low expression but not those with high expression
      of HSD11B2. Demethylation induced by 5-aza-2'-deoxycytidine and procainamide
      enhanced the transcription and activity of the 11 beta HSD2 enzyme in human cells
      in vitro and in rats in vivo. Methylation of HSD11B2 promoter-luciferase
      constructs decreased transcriptional activity. Methylation of recognition
      sequences of transcription factors, including those for Sp1/Sp3, Arnt, and
      nuclear factor 1 (NF1) diminished their DNA-binding activity. Herein NF1 was
      identified as a strong HSD11B2 stimulatory factor. The effect of NF1 was
      dependent on the position of CpGs and the combination of CpGs methylated. A
      methylated-CpG-binding protein complex 1 transcriptional repression interacted
      directly with the methylated HSD11B2 promoter. These results indicate a role for
      DNA methylation in HSD11B2 gene repression and suggest an epigenetic mechanism
      affecting this gene causally linked with hypertension.

PMID- 15489964
TI  - ASCI Presidential Address: Mentoring and teaching clinical investigation.

PMID- 15489963
TI  - Constitutive activity of the melanocortin-4 receptor is maintained by its N
      terminal domain and plays a role in energy homeostasis in humans.
AB  - The melanocortin-4 receptor (MC4R), a centrally expressed G protein-coupled
      receptor (GPCR), is essential for the maintenance of long-term energy balance in
      humans. Mutations in MC4R are the most common genetic cause of obesity. Since
      activation of this receptor leads to a decrease in food intake, MC4R is also a
      major therapeutic target for the treatment of obesity. Control of MC4R activity
      in vivo is modulated by the opposing effects of the anorexigenic agonist alpha
      melanocyte-stimulating hormone (alpha-MSH) and the orexigenic antagonist agouti
      related protein (AGRP). In addition, experiments in vitro have demonstrated that
      the human MC4R has an intrinsic constitutive activity on which AGRP also acts as
      an inverse agonist. The physiological role of this constitutive activity in the
      control of energy balance as well as the domain of the protein implicated in its
      maintenance are unknown. By systematically studying functional defects in
      naturally occurring MC4R mutations from obese patients, we defined a cluster of N
      terminal mutations that selectively impair the constitutive activity of the
      receptor. Further characterization of this domain demonstrated that it functions
      as a tethered intramolecular ligand that maintains the constitutive activity of
      MC4R and may provide novel avenues for the design of drugs targeting this
      receptor. Our results also suggest that the tonic satiety signal provided by the
      constitutive activity of MC4R may be required for maintaining long-term energy
      homeostasis in humans.

PMID- 15489965
TI  - AAP Presidential Address: The AAP and the transformation of medicine.

PMID- 15489966
TI  - Presentation of the 2004 Kober Medal to K. Frank Austen.

PMID- 15489967
TI  - Acceptance of the Kober Medal: It only gets better.

PMID- 15489968
TI  - Mechanistic analogies amongst carbohydrate modifying enzymes.
AB  - Carbohydrates are known to play essential roles in a myriad of biological
      processes. The enormous complexity of the various oligosaccharide structures
      found in biology is derived from a rational orchestration of the enzymatic
      formation and breakdown of glycosidic linkages achieved by glycosyltransferases,
      glycosidases and phosphorylases. A detailed understanding of the chemical
      mechanisms by which these classes of enzymes function not only provides a
      rational basis for their engineering and application in both the development and
      synthesis of new classes of therapeutic agents, but also provides insight into
      the role of convergence in the natural evolution of enzyme function.

PMID- 15489969
TI  - Light metal hydrides and complex hydrides for hydrogen storage.
AB  - The availability of feasible methods for hydrogen storage is one of the key-maybe
      the key-requirements for the large scale application of PEM fuel cells in cars.
      There are in principle four different approaches, i.e. cryostorage in liquid
      form, high pressure storage, storage in the form of a chemical compound which is
      converted to hydrogen by on-board reforming, or reversible chemical storage in
      different kinds of storage materials. New developments in the field of chemical
      storage make such systems attractive compared to the other options. This review
      will discuss the different possibilities for chemical storage of hydrogen and the
      focus on the presently most advanced system with respect to storage capacity and
      kinetics, i.e. catalyzed alanates, especially NaAlH(4).

PMID- 15489971
TI  - Shuttling through reversible covalent chemistry.
AB  - The first stimuli-responsive molecular shuttle that functions through reversible
      C-C bond formation is reported.

PMID- 15489970
TI  - Rapid cloning and expression of a fungal polyketide synthase gene involved in
      squalestatin biosynthesis.
AB  - PCR primers designed to selectively amplify the unique C-methyltransferase domain
      of fungal polyketide synthases were used to selectively clone a polyketide
      synthase gene involved in the biosynthesis of the squalene synthase inhibitor
      squalestatin S1 , heterologous expression of which led to the biosynthesis of the
      squalestatin side-chain.

PMID- 15489972
TI  - Solvent-mediated self-association of a Horning-crown macrocycle.
AB  - A member of a new class of novel macrocycles possessing both polyether and
      phenolic functionalities, forms dimers in both the solid-state and in solution
      when exposed to chloroform, dichloromethane or toluene, but does not self
      associate in the presence of dimethyl sulfoxide.

PMID- 15489973
TI  - A metallo-capped polyrotaxane containing calix[4]arenes and cyclodextrins and its
      highly selective binding for Ca2+.
AB  - A water-soluble nanometer-scale metallocapped polyrotaxane has been prepared by
      the inclusion complexation of azo-calixarenes with metallo-bridged bis(beta-CD)s,
      displaying highly selective binding for Ca(2+).

PMID- 15489974
TI  - Supramolecular isomerism in spin crossover networks with aurophilic interactions.
AB  - Assembly of Fe(II), 3-cyanopyridine and [Au(CN)2](-) affords, in one-pot
      reaction, three coordination polymers that represent a genuine example of
      supramolecular isomerism with strong influence in the spin crossover regime of
      the Fe(II) ions.

PMID- 15489975
TI  - Molecular tectonics: design of luminescent H-bonded molecular networks.
AB  - Using bis-amidinium dications as tetra H-bond donor tectons and Au(CN)(2)(-)
      anion, neutral 1-D networks based on a bis monohapto mode of H-bonding are
      obtained. Owing to the short metal-metal distance within the network, luminescent
      crystals are obtained. The emission phenomena may be tuned by the nature of the
      spacer connecting the two cyclic amidinium groups.

PMID- 15489976
TI  - Self-oriented pseudoisocyanine J-aggregates in solution.
AB  - Highly oriented fiber-shaped J-aggregates of pseudoisocyanine (PIC) molecules
      were prepared by simply growing the aggregates in a narrow glass cell, which
      allows evaporation of the solution in one direction.

PMID- 15489977
TI  - New high-nuclearity Ni-Pt carbonyl clusters: synthesis and X-ray structure of the
      ordered [HNi24Pt17(CO)46]5- and the substitutionally Ni/Pt disordered
      [Ni32Pt24(CO)56]6- cluster anions.
AB  - Condensation between preformed Ni-Pt and Pt carbonyl clusters leads to the new
      [H(6-n)Ni(24)Pt(17)(CO)(46)](n-)(n= 5, 6) and the substitutionally Ni/Pt
      disordered [Ni(24)(Ni(12-x)Pt(x))Pt(20)(CO)(56)](6-) (x = 4) carbonyl clusters,
      the latter of which represents the highest nuclearity homoleptic carbonyl cluster
      anion so far reported.

PMID- 15489978
TI  - Supramolecular complex composed of a covalently linked zinc porphyrin dimer and
      fulleropyrrolidine bearing two axially coordinating pyridine entities.
AB  - A zinc porphyrin dimer-fullerene supramolecular complex with a large association
      constant is assembled; efficient intramolecular photoinduced electron transfer
      from the singlet excited state of zinc porphyrin to the fullerene is observed.

PMID- 15489980
TI  - Ultrasonic cavitation in microspace.
AB  - Ultrasound was irradiated to a micro-1D and -2D space having a characteristic
      length of 200 microm, and the presence of cavitation was confirmed from video
      images, and the generation of OH radicals, which was quantitatively evaluated
      with fluorometry.

PMID- 15489979
TI  - An enantioselective imprinted receptor for Z-glutamate exhibiting a binding
      induced color change.
AB  - Using 1-(4-styryl)-3-(3-nitrophenyl)urea as host monomer for the imprinting of Z
      (D or L)-Glu, a polymeric receptor exhibiting strong enantioselectivity and a
      change in color intensity upon binding of the guest was obtained.

PMID- 15489981
TI  - Ring-closing metathesis in biphasic BMI.PF6 ionic liquid/toluene medium: a
      powerful recyclable and environmentally friendly process.
AB  - Biphasic BMI[middle dot]PF(6)/toluene solvent is a remarkably suitable and clean
      medium for performing olefin metathesis with a new 2nd generation ionic liquid
      supported-ruthenium catalyst: high levels of recyclability and reusability
      combined with a high reactivity were obtained with a variety of di- or tri
      substituted and/or oxygen-containing dienes, and very low residual ruthenium
      levels were detected (1 to 22 ppm) in the products.

PMID- 15489982
TI  - Mesoporous silica anchored Ru catalysts for highly enantioselective hydrogenation
      of beta-ketoesters.
AB  - Recyclable and reusable mesoporous silica anchored Ru catalysts based on 4,4'
      substituted BINAPs were synthesized and used for the hydrogenation of beta-alkyl
      beta-ketoesters with up to 98.6% e.e. and beta-aryl beta-ketoesters with up to
      95.2% e.e.

PMID- 15489983
TI  - High-efficiency and minimum-waste continuous kinetic resolution of racemic
      alcohols by using lipase in supercritical carbon dioxide.
AB  - A novel continuous-flow scCO(2) process for kinetic resolution of racemic
      alcohols can be performed with an immobilized lipase to lead to a quantitative
      mixture of the corresponding optically active acetates with up to 99% ee and
      unreacted alcohols with up to 99% ee, in which the productivity of the optically
      active compounds was improved by over 400 times compared to the corresponding
      batch reaction using scCO(2).

PMID- 15489984
TI  - Convenient magnesiation of aromatic and heterocyclic rings bearing a hydroxy
      group in presence of LiCl.
AB  - The reaction of various iodophenols with MeMgCl in presence of LiCl followed by
      the addition of i-PrMgCl provides the corresponding magnesiated magnesium
      phenolates as THF soluble reagents; this approach can be extended to heterocyclic
      compounds bearing a hydroxy group like pyridines and quinolines.

PMID- 15489985
TI  - Semi-quantitative estimation by IR of framework, extraframework and defect Al
      species of HBEA zeolites.
AB  - A simple method based on the characterization (composition, Bronsted and Lewis
      acidities) of acid treated HBEA zeolites was developed for estimating the
      concentrations of framework, extraframework and defect Al species.

PMID- 15489986
TI  - A novel, stereoselective and convergent synthesis of aryltetralins.
AB  - A novel one-pot, two-component condensation reaction between readily available
      allylsiloxanes and electron-rich aldehydes generates aryltetralins with complete
      control of stereochemistry.

PMID- 15489987
TI  - Microwave induced preparation of a-axis oriented double-ended needle-shaped ZnO
      microparticles.
AB  - Microwave irradiation of solutions of Zn(NO3)2 and urea provides a
      straightforward route to a-axis oriented crystals of needle-like morphology.

PMID- 15489988
TI  - Novel aggregation of [Ni(thiolato)2(amine)2]-type square planes assisted by
      silver(I) ions.
AB  - Treatment of [Ni(L)][L =((-)SCH(2)CH(2)NH[double bond, length as m-dash]C(CH(3))
      )(2)] with Ag(+) in water gave a pinwheel-like S-bridged Ni(II)(3)Ag(I)(2)
      structure in [Ag(2)[Ni(L)](3)](2+), which further reacted with [Ni(L)] to produce
      a Ni(II)(4)Ag(I)(2) structure in [Ag(2)[Ni(L)](4)](2+) and a Ni(II)(7)Ag(I)(4)
      structure in [Ag(4)[Ni(L)](7)](4+).

PMID- 15489989
TI  - Low-temperature synthetic method for size-controlled CdSe nanocrystals:
      utilization of boron selenide.
AB  - By employing B(2)Se(3) as a selenium source, we demonstrate that at reaction
      temperatures as low as 60 [degree]C, relatively monodisperse, fluorescent CdSe
      nanocrystals can be conveniently prepared in various sizes selected from 2 to 13
      nm.

PMID- 15489990
TI  - Electronic and vibrational properties of a MOF-5 metal-organic framework: ZnO
      quantum dot behaviour.
AB  - UV-Vis DRS and photoluminescence (PL) spectroscopy, combined with excitation
      selective Raman spectroscopy, allow us to understand the main optical and
      vibrational properties of a metal-organic MOF-5 framework. A O(2
      )Zn(2+)[rightward arrow] O(-)Zn(+) ligand to metal charge transfer transition
      (LMCT) at 350 nm, testifies that the Zn(4)O(13) cluster behaves as a ZnO quantum
      dot (QD). The organic part acts as a photon antenna able to efficiently transfer
      the energy to the inorganic ZnO-like QD part, where an intense emission at 525 nm
      occurs.

PMID- 15489991
TI  - LiSr2(NCN)I3: the first empty tetrahedral strontium(II) entity coordinated by
      carbodiimide units but without strontium-strontium bonding.
AB  - LiSr(2)(NCN)I(3), the first extended compound containing empty tetrahedral Sr(4)
      entities, is synthesized using a new flux route, and it exhibits two
      interpenetrating three-dimensional networks made up from Sr tetrahedra capped by
      NCN(2-) anions on their triangular faces and vertex-sharing LiI(6) octahedra.

PMID- 15489992
TI  - H2-O2 atmosphere increases the activity of Pt/TiO2 for benzene photocatalytic
      oxidation by two orders of magnitude.
AB  - Unprecedented photocatalytic activity and durability of Pt/TiO(2) for decomposing
      persistent organic pollutants (e.g. benzene) have been obtained by adding trace
      H(2) into an O(2)-rich photooxidation system.

PMID- 15489993
TI  - Synthesis of monodisperse iron oxide nanocrystals by thermal decomposition of
      iron carboxylate salts.
AB  - Iron oxide (Fe(3)O(4), magnetite) nanocrystals of 6 to 30 nm with narrow size
      distributions (sigma = 5-10%) were prepared by the pyrolysis of iron carboxylate
      salts.

PMID- 15489994
TI  - Stoichiometric and catalytic reductive aldol cyclizations of alkynediones induced
      by Stryker's reagent.
AB  - Conjugate reduction of alkynones by stoichiometric [(Ph(3)P)CuH](6) or catalytic
      [(Ph(3)P)CuH](6) and polymethyl-hydrosiloxane proceeds to cyclization by an aldol
      reaction with tethered ketones to generate [small beta]-hydroxyenones with good
      diastereoselectivity.

PMID- 15489995
TI  - Azobenzene derivatives with a long alkyl chain and aminoxyls.
AB  - A trans-azobenzene derivative with a long alkyl chain and a TEMPO radical showed
      photo-induced isomerization to become the corresponding cis-isomer with a
      significant change of its intermolecular magnetic interaction from a weak
      ferromagnetic one based on the CW model to a relatively strong antiferromagnetic
      one based on the ST model with the J-value of 36.7 K.

PMID- 15489996
TI  - Advanced selective optical sensors based on periodically organized mesoporous
      hybrid silica thin films.
AB  - Mesoporous thin films functionalized with silylated [small beta]-diketone
      compounds with symmetry mesostructure dependent on the probe quantity were used
      as fast uranyl species sensors with high selectivity and sensitivity.

PMID- 15489997
TI  - A regioregular polyalkylthiophene bearing covalently-linked biotin, and its
      interaction with avidin in solution and in thin films.
AB  - A regioregular copolymer of 3-hexylthiophene and 3-(6-hydroxyhex-1-yl)thiophene
      has been functionalised with biotin hydrazide; binding of avidin to the biotin
      moieties causes drastic changes to the absorption spectrum of the polymer in
      solution, and to the electrochemistry and conductivity of the polymer in thin
      films.

PMID- 15489998
TI  - Superhydrophobic silica aerogels by fluorination at the gel stage.
AB  - Superhydrophobic silica aerogels are obtained by surface modification of standard
      silica gels prepared by a two-step process with a heavily fluorinated silyl
      chloride followed by supercritical evacuation of the solvent.

PMID- 15489999
TI  - Mechanistic and stereochemical aspects of the asymmetric cyclocarbonylation of
      1,6-enynes with rhodium catalysts.
AB  - NMR and kinetic investigations of the cyclocarbonylation of 1,6-enynes with
      cationic rhodium(i) catalysts, modified with atropisomeric diphosphines, disprove
      the involvement of carbonyl species for 1,6-enyne activation; low-temperature
      catalysis, with molecular sieves as the carbon monoxide reservoir, is highly
      enantioselective (ee up to 97%).

PMID- 15490000
TI  - Coordination of pertechnetate [TcO4]- to actinides.
AB  - The ability of [TcO(4)](-) to coordinate directly to tetra- and hexa-valent
      actinides in the presence of organic P[double bond, length as m-dash]O ligands is
      confirmed in the crystallographically characterised complexes
      [UO(2)(TcO(4))(2)(Ph(3)PO)(3)] and [Th(TcO(4))(4)((n)Bu(3)PO)(4)].

PMID- 15490001
TI  - The rediscovery of Alfred Werner's second hexol.
AB  - A compound originally prepared by Alfred Werner but structurally misassigned has
      been shown by three independent X-ray structural analyses to be a hexanuclear
      species which can now be regarded as Werner's second hexol, his first being that
      famous for being the first non-carbon containing species to be optically
      resolved.

PMID- 15490002
TI  - Practical highly enantioselective synthesis of terminal propargylamines. An
      expeditious synthesis of (S)-(+)-coniine.
AB  - The one-pot three-component addition reaction of trimethylsilylacetylene,
      aldehydes and dibenzylamine provides in the presence of CuBr/Quinap as catalyst,
      various enantiomerically enriched propargylamines in good yields (up to 99%) and
      excellent enantiomeric excess (up to 98%ee) which can be used as a key
      intermediate in the synthesis of the alkaloid (S)-(+)-coniine.

PMID- 15490003
TI  - Carbon dioxide-expanded liquid substrate phase: an effective medium for selective
      hydrogenation of cinnamaldehyde to cinnamyl alcohol.
AB  - It has been shown that CO(2)-expanded cinnamaldehyde liquid phase is a unique and
      effective medium for cinnamaldehyde hydrogenation to cinnamyl alcohol, due to
      interactions between the C[double bond, length as m-dash]O group of the substrate
      and CO(2) molecules and increased solubility of H(2).

PMID- 15490004
TI  - Energy harvesting star-shaped molecules for electroluminescence applications.
AB  - Novel energy harvesting molecules featuring hexaarylbenzene based triarylamine
      donors and a dithienyl benzothiadiazole acceptor, and that emit red light in
      electroluminescent devices, have been prepared for the first time.

PMID- 15490005
TI  - First asymmetric SmI2-induced cross-coupling of Cr(CO)3 aromatic nitrone
      complexes with carbonyl compounds.
AB  - The SmI(2)-induced cross-coupling of Cr(CO)(3)-complexed nitrones with carbonyl
      compounds is described. This highly chemo- and diastereoselective reaction
      affords enantiopure [small beta]-amino alcohol complexes in excellent yields.

PMID- 15490006
TI  - Penicillins as beta-lactamase-dependent prodrugs: enabling role of a vinyl ester
      exocyclic to the lactam ring.
AB  - Incorporation of a vinyl ester exocyclic to the beta-lactam ring of a penicillin
      nucleus enables this to act as a beta-lactamase-dependent prodrug - rapid release
      of the (unactivated) alkoxy component of the vinyl ester is triggered by enzyme
      catalysed hydrolysis of the beta-lactam ring, whilst buffer-catalysed hydrolysis
      of the structure at neutral pH is particularly slow.

PMID- 15490007
TI  - A new approach to the synthesis of conjugated polymer-nanocrystal composites for
      heterojunction optoelectronics.
AB  - We report a simple one pot process for the preparation of lead sulfide (PbS)
      nanocrystals in the conjugated polymer poly (2-methoxy-5-(2'ethyl-hexyloxy)-p
      phenylene vinylene)(MEH-PPV), and we demonstrate electronic coupling between the
      two components.

PMID- 15490008
TI  - An active ferrocenyl triarylphosphine for palladium-catalyzed Suzuki-Miyaura
      cross-coupling of aryl halides.
AB  - Pd-catalyzed Suzuki-Miyaura reaction of aryl chlorides was accomplished through
      the use of an active ferrocene-based triarylphosphine ligand. This air- and
      moisture-stable ligand was found to be effective for the cross-coupling of aryl
      halides at room temperature to 115 degrees C.

PMID- 15490009
TI  - A novel strategy for the preparation of arylhydroxylamines: chemoselective
      reduction of aromatic nitro compounds using bakers' yeast.
AB  - Using bakers' yeast as a biocatalyst, the chemoselective reduction of aromatic
      nitro compounds bearing electron-withdrawing groups gave the corresponding
      hydroxylamines with good to excellent conversion under mild conditions.

PMID- 15490010
TI  - Oligomer preparation from hexane by radical polyaddition with bis(alpha
      trifluoromethyl-beta,beta-difluorovinyl) terephthalate.
AB  - Polymer preparation from hexane as a starting material by radical polyaddition
      with bis(alpha-trifluoromethyl-beta,beta-difluorovinyl) terephthalate
      [CF(2)=C(CF(3))OCOC(6)H(4)COO-C(CF(3))=CF(2)] was investigated to afford polymers
      bearing a molecular weight of as high as 5.5 x 10(3), and the polyaddition
      mechanism including 1,5-radical shift mechanism was proposed.

PMID- 15490011
TI  - Strongly red-fluorescent novel donor-pi-bridge-acceptor-pi-bridge-donor (D-pi-A
      pi-D) type 2,1,3-benzothiadiazoles with enhanced two-photon absorption cross
      sections.
AB  - Novel donor-pi-bridge-acceptor-pi-bridge-donor (D-pi-A-pi-D) type 2,1,3
      benzothiadiazole fluorescent dyes connected to the N,N-diarylamino terminus via
      various type pi-conjugate spacers exhibits large two-photon absorption cross
      sections and high fluorescent quantum yields in orange-red color.

PMID- 15490012
TI  - Metal-chelating nanoparticles as selective fluorescent sensor for Cu2+.
AB  - A fluorescent sensor for Cu(2+) at the nanomolar level in water has been designed
      by associating a BODIPY fluorophore and a selective ligand (cyclam) in ultrafine
      polymer nanoparticles.

PMID- 15490013
TI  - Structure and protonation of the bis-ethylene adduct [Pt(micro-PBut2)(eta2
      CH2=CH2)]2. Pt-H-P agostic interaction and proton scrambling.
AB  - The bis-ethylene derivative [Pt(micro-PBu(t)(2))(eta(2)-CH(2)=CH(2))](2) was
      prepared and characterized by X-ray diffraction; its protonation affords
      [Pt(2)(micro-PBu(t)(2))(micro-PBu(t)(2)H)(eta(2)-CH(2)=CH(2))(2)](CF(3)SO(3)),
      with a rarely observed P-H-M agostic proton in rapid exchange with those of the
      adjacent ethylene molecule.

PMID- 15490014
TI  - Self-assembly of a 1D heterotrimetallic Cu(II)-Sr(II)-Na(I) propeller-like chiral
      coordination polymer with ferromagnetic interactions.
AB  - Self-assembly of metalloligand [CuL](-)(H(3)L =N-5-bromosalicylaldehydeglycyl-l
      tyrosine) with Sr(2+) and Na(+) results in a 1D micro(2)-carboxylate- and H(2)O
      bridged heterotrimetallic chiral coordination polymer
      [[Na(CuL)(3)Sr(H(2)O)(3)].9H(2)O]](n), which exhibits weak ferromagnetic exchange
      interactions and optical activity.

PMID- 15490015
TI  - Polyaniline superstructures created by a templating effect of organogels.
AB  - The use of organogelators to template chiral and achiral polyaniline
      superstructures via the electrostatic interaction between anionic sulfonated
      polyaniline and a cationic gelator is described.

PMID- 15490016
TI  - Inorganic polymer-derived hollow SiC and filled SiCN sphere assemblies from a
      3DOM carbon template.
AB  - Three-dimensional long range ordered hollow SiC and filled SiCN sphere assemblies
      were prepared for the first time by embedding low molecular weight pre-ceramic
      polymers of polymethylsilane and polysilazane into sacrificial 3DOM carbon
      templates which were subsequently burned out in air after pyrolysis under a
      nitrogen atmosphere.

PMID- 15490017
TI  - Isolation of equatorial conformers of chloro- and bromocyclohexane in a pure
      state as inclusion complexes with a host compound.
AB  - The equatorial conformers of chloro- and bromocyclohexane were isolated in a pure
      state as inclusion complexes with a host compound, and their structures were
      studied by IR spectra and X-ray analysis.

PMID- 15490018
TI  - Spectrophotometric, EPR and kinetic characterisation of the >N-O* radical from 1
      hydroxybenzotriazole, a key reactive species in mediated enzymatic oxidations.
AB  - Characterisation of the aminoxyl (>N-O*) radical BTNO, generated from 1
      hydroxybenzotriazole (HBT) by the one-electron oxidant CAN (a Ce(IV) salt),
      confirms BTNO as the reactive intermediate in oxidations run with the laccase/HBT
      system.

PMID- 15490019
TI  - Irreversible or reversible self-assembly procedures yield robust zirconium (IV)
      porpyrinphosphonate cones or microm-long fibers of monomolecular thickness.
AB  - Stepwise, irreversible self-assembly of porphyrinphosphonates by zirconium(IV)
      produces cones of 20 nm height and similar widths. Side-on growth cannot be
      prevented. Reversible fiber growth without metal ions gave micrometer long fibers
      on mica of 2 nm width, because charge repulsion allowed only for end-on growth.

PMID- 15490020
TI  - Polyaniline nanofibers: chemical synthesis using surfactants.
AB  - Nanofibers of doped polyaniline.HCSA having diameters 1-2 nm are observed in TEM
      images of bath sonicated aqueous dispersions of larger nanofibers (30-50 nm
      diameter) synthesized by surfactant-assisted chemical oxidative polymerization of
      aniline in dilute aqueous organic acids.

PMID- 15490021
TI  - The first palladium-catalyzed 1,4-addition of terminal alkynes to conjugated
      enones.
AB  - The first palladium-catalyzed 1,4-addition of terminal alkynes to conjugated
      enones has been developed in water and in acetone, producing the corresponding
      gamma,delta-alkynyl ketones in high yields.

PMID- 15490023
TI  - Nosocomial bloodstream infection in human immunodeficiency virus-infected
      patients in Taiwan: descriptive epidemiology and risk factors for mortality.
AB  - BACKGROUND AND PURPOSE: Nosocomial bloodstream infection (NBSI) is common in
      patients with human immunodeficiency virus (HIV) infection. This study evaluated
      the incidence, causative pathogens, and outcome of NBSIs in hospitalized HIV
      infected patients at a university hospital in Taiwan. METHODS: The medical
      records of all HIV-infected patients who developed NBSIs from June 1994 to June
      2003 were retrospectively reviewed. A standardized case record form was used to
      collect demographic, clinical, laboratory, and microbiologic data. RESULTS:
      During the study period, 57 episodes of NBSIs occurred in 51 HIV-infected
      patients whose median age was 37 years (range, 23 to 60 years). All of the
      patients were at HIV infection stage C. The incidence of NBSIs was 2.3 per 1000
      person-days of hospitalization (41.4 per 1000 discharges). More than three
      fourths of the 57 episodes (77.2%) were classified as primary NBSIs. Other
      infection foci included respiratory tract (6 episodes), urinary tract (3),
      surgical site (2), and skin (2). Staphylococcus species were the leading
      pathogens (42.1%). The crude and attributable mortality rates in patients with
      NBSIs during the study period were 38.6% and 26.1%, respectively. Multivariate
      analysis using a logistic regression model revealed that shock and
      hypoalbuminemia at the onset of NBSIs were the 2 factors predictive of mortality.
      CONCLUSIONS: NBSIs in hospitalized patients in the late stage of HIV infection
      were associated with a high attributable mortality rate. Staphylococcus species
      were the leading pathogen responsible for NBSIs. Presentations of shock and
      hypoalbuminemia were predictive of mortality.

PMID- 15490024
TI  - Hand-assisted versus total laparoscopic live donor nephrectomy.
AB  - BACKGROUND AND PURPOSE: The optimal minimally invasive procedure to procure live
      donor kidneys for renal transplantation has not been established. This study
      compared the donor outcome of hand-assisted laparoscopic live donor nephrectomy
      (H-LLDN) with total laparoscopic live donor nephrectomy (T-LLDN). METHODS: The
      outcomes of 12 donors undergoing H-LLDN were compared to that of a subsequent
      series of 12 donors undergoing T-LLDN. Body mass index, operation time, warm
      ischemia time, hospital stay, surgical complications, and short-term graft
      function were compared between the 2 groups. RESULTS: LLDN was successfully
      performed in all 24 donors. Both approaches resulted in excellent early graft
      function. The mean operation time in T-LLDN (215 minutes) was slightly shorter
      than that in H-LLDN (258 minutes), suggesting that the skills developed as
      surgeons learned the H-LLDN procedure had transferred to their performance of T
      LLDN. The mean warm ischemia time of the T-LLDN group (4.5 minutes) was longer
      than that of the H-LLDN group (3.8 minutes), although this difference was not
      significant. One minor tear of the lumbar vein occurred in the H-LLDN group and
      the resultant bleeding necessitated blood transfusion. One mechanical failure
      occurred when the renal vein was divided by endoscopic gastrointestinal
      anastomosis in the T-LLDN group. The length of hospital stay, resumption of diet,
      and the use of narcotic analgesics were not different between the 2 groups.
      CONCLUSIONS: Both H-LLDN and T-LLDN are safe and effective approaches for the
      procurement of live donor kidneys. The benefits of the H-LLDN technique include
      direct manual control of the operative field and increased safety margin. The
      development of a hospital LLDN program by starting with a hand-assisted approach
      may reduce the potential bleeding complications and facilitate the safe
      transition to the cosmetically preferable total laparoscopic approach.

PMID- 15490025
TI  - Clinical characteristics and prognostic determinants of infective endocarditis in
      adult intravenous drug users.
AB  - BACKGROUND AND PURPOSE: Infective endocarditis (IE), one of the most serious
      complications of intravenous (IV) drug use, has been increasing in incidence in
      the past decade in Taiwan. The difference in prognostic determinants for IE
      between patients with and without IV drug use is poorly understood. This study
      investigated the clinical profile and prognostic determinants of IE in IV drug
      users. METHODS: The medical records for 157 episodes (30 episodes in IV drug
      users and 127 episodes in non-drug users) of IE in 143 consecutively hospitalized
      patients were retrospectively evaluated. Independent prognostic determinants were
      identified by multiple Cox proportional hazards regression analysis. RESULTS: IV
      drug users were younger with a predominance of males. They also had a higher
      frequency of right-sided IE, underlying disease, and had a larger area of
      vegetation than non-drug users. Staphylococci were the most common causative
      microorganisms in IV drug users while streptococci were more common in non-drug
      users. Septic pulmonary embolism and septic complications were more frequent in
      IV drug users. In-hospital mortality was similar between the 2 groups. Non
      cardiac shock was the only significant prognostic determinant in IV drug users
      (odds ratio [OR] 15.5; 95% confidence interval [CI] 3.0 to 81.5); however, in non
      drug users, non-cardiac shock (OR, 4.4; 95% CI, 2.0 to 9.8), older age (> or = 50
      years), and neurological complications were independent predictors of in-hospital
      mortality. CONCLUSIONS: The clinical characteristics and prognostic determinants
      of IE in IV drug users were significantly different from those of non-drug users.
      IV drug users were less likely to have a benign clinical course and had a higher
      frequency of septic complications. These findings indicate the importance of risk
      stratification and modified treatment strategy in IV drug users who develop IE.

PMID- 15490026
TI  - Necrotizing enterocolitis in infants: clinical outcome and influence on growth
      and neurodevelopment.
AB  - BACKGROUND AND PURPOSE: Necrotizing enterocolitis (NEC) is a gastrointestinal
      emergency in neonates. Whether NEC affects infants' growth and development is
      controversial. The purpose of this study was to explore the clinical
      characteristics and outcome and to assess the effect of NEC on growth and
      neurodevelopment in infants. METHODS: A total of 80 neonates admitted to the
      neonatal intensive care unit from January 1991 to April 2002 with definite,
      advanced NEC, including 48 with modified Bell's stage II and 32 with stage III.
      Sixty six of the patients were premature. Very low birth weight (VLBW) preterm
      infants without NEC were used as matching controls for the 15 infants with VLBW.
      The growth and neurodevelopment of patients and controls were assessed using the
      Bayley Scales of Infant Development-II and compared at 6 and 18 months of
      corrected age. RESULTS: NEC developed an average of 27.7 days after feeding
      began. The most common initial signs were abdominal distension, decreased
      activity, hematochezia, and abdominal tenderness. Thirty four patients (43%)
      required surgical intervention. Three infants developed short bowel syndrome
      after surgical resection. The overall mortality was 24% (19/80) and was mostly
      associated with extensive bowel involvement and NEC-related sepsis or multiple
      organ failure. Of the surviving 61 infants, 12 (20%) developed intestinal
      strictures, 2 in the ileum, 6 in the colon, and 4 in both ileum and colon.
      Compared with controls, the VLBW infants with NEC were shorter and had delayed
      psychomotor development at 18 months of corrected age. Mental development,
      however, did not differ significantly. CONCLUSIONS: Intestinal stricture was the
      most common gastrointestinal complication in this series of infants with NEC.
      Besides the bowel sequelae, VLBW infants who survive NEC are at risk for
      impairment of growth and neurodevelopment.

PMID- 15490027
TI  - Delayed gastric emptying after pylorus-preserving pancreaticoduodenectomy.
AB  - BACKGROUND AND PURPOSE: Pylorus-preserving pancreaticoduodenectomy is associated
      with a high incidence of delayed gastric emptying. The aim of this study was to
      determine the incidence and risk factors for delayed gastric emptying after this
      procedure. METHODS: This retrospective study included 63 consecutive patients who
      received pylorus-preserving pancreaticoduodenectomy from July 1993 to December
      2002. The patients were divided into 2 groups based on the presence of delayed
      gastric emptying. Preoperative indices, postoperative morbidity, nasogastric
      intubation, and hospital stay were compared. The risk factors for delayed gastric
      emptying were analyzed. RESULTS: The postoperative incidence of delayed gastric
      emptying was 44% (28/63 patients). Multivariate analysis revealed that no
      preoperative biliary drainage, no cholestatic change in the liver and blood loss
      > 400 mL were significant risk factors for delayed gastric emptying. CONCLUSIONS:
      Pylorus-preserving pancreaticoduodenectomy is a safe procedure with a high
      incidence of delayed gastric emptying. Delicate surgical dissection to decrease
      blood loss and the extent of perigastric inflammation may be the key factor to
      prevent delayed gastric emptying.

PMID- 15490028
TI  - Psychometric evaluation of the Taiwan version of the Disability of the Arm,
      Shoulder, and Hand (DASH) questionnaire.
AB  - BACKGROUND AND PURPOSE: To adapt the Taiwan version of the Disability of the Arm,
      Shoulder, and Hand (DASH) questionnaire and evaluate its psychometric properties.
      METHODS: The DASH questionnaire was adapted through the process of translation,
      back-translation, and expert review. Eighty two subjects with upper extremity
      disorders were recruited in a medical center and 46 of these patients could be
      followed up to assess retest reliability in less than 10 days. Cronbach alpha and
      intraclass correlation coefficient were used to evaluate the internal consistency
      and test-retest reliability. Principal axis factor analysis was performed to
      assess the factor-construct validity, while concurrent validity was tested with
      the Medical Outcomes Study Short Form-36 (SF-36) Taiwan version questionnaire.
      RESULTS: The internal consistency of the Taiwan version of the DASH questionnaire
      was high (Cronbach alpha = 0.96) and the test-retest reliability was satisfactory
      (intraclass correlation coefficient = 0.9). Principal axis factor analysis
      confirmed the 1-factor model. The Pearson correlation coefficients of the DASH
      questionnaire to the SF-36 showed a correlation with physical component summary
      scores rather than mental component summary scores. Bodily pain, physical
      function and role-physical scores among the SF-36 subscales were most
      significantly correlated with DASH disability/symptom scores. CONCLUSION: The
      Taiwan version of the DASH questionnaire is a valid and reliable measure of
      health status for patients with upper-extremity disorders.

PMID- 15490029
TI  - Exercise-provoked bidirectional ventricular tachycardia in a young woman.
AB  - Exercise-induced ventricular tachycardia (VT) is rare in children and young
      adults without structural heart disease. Catecholaminergic polymorphic VT (CPVT)
      is among the possible causes and carries a poor prognosis. The QRS morphology of
      CPVT can be bidirectional, polymorphic or even ventricular fibrillation. We
      report a case of CPVT initially presenting as sudden collapse in an 18-year-old
      Taiwanese woman. Family history was negative for arrhythmias and sudden death.
      Laboratory analyses, transthoracic echocardiography, magnetic resonance imaging,
      electrophysiological study including procainamide and isoproterenol test were all
      negative. Bidirectional VT was induced by treadmill exercise test. She responded
      well to beta-blocker therapy. Some cases of CPVT are sporadic and some occur in
      patients with a family history. The treatment of choice for this disease is beta
      blocker and implantation of an internal cardioverter defibrillator.

PMID- 15490030
TI  - Primary pulmonary botryomycosis with parietal pleura involvement.
AB  - Botryomycosis is a rare chronic suppurative disease characterized by the presence
      of eosinophilic granules containing the causative bacteria on histological study
      of an abscess specimen. The majority of cases involve the skin and visceral
      involvement is rare. A 54-year-old man with primary pulmonary botryomycosis which
      involved parietal pleura presented with exertional dyspnea for 2 weeks. Echo
      guided aspiration of lung mass yielded viridans streptococci and positive Gram
      stain of the surgical specimen indicated viridians streptococci was the causative
      pathogen. There was no recurrence during 2 years of follow-up after surgery and
      antibiotic treatment. Early differentiation of botryomycosis from lung cancer,
      pulmonary tuberculosis, and actinomycosis is essential.

PMID- 15490031
TI  - Clinicopathology of severe acute respiratory syndrome: an autopsy case report.
AB  - In mid-April 2003, a major outbreak of severe acute respiratory syndrome (SARS)
      developed in Taiwan. During the outbreak, SARS-associated coronavirus (SARS-CoV)
      was documented in 346 patients and 73 of them died. Autopsy was performed in 9 of
      the suspected SARS patients who died during the outbreak, but SARS was the cause
      of death in only 1 of these patients. Here we report the histological features of
      this patient and their clinicopathological correlations. The patient, a 36-year
      old Indonesian woman, was a caretaker working for a Taiwanese family. She stayed
      in Taipei Jen-Chi Hospital from April 10 to April 19 to take care of her elderly
      employer. She developed fever on April 21 and respiratory distress on April 25,
      and received ribavirin, intravenous immunoglobulin, and steroid. The respiratory
      distress persisted and worsened, and intubation was performed on April 27. The
      respiratory condition improved initially after mechanical ventilation, but
      subcutaneous emphysema and pneumomediastinum developed on May 1. Her condition
      deteriorated rapidly and she died on May 2, 11 days after the onset of fever.
      Autopsy was performed on the same day. Histologically, the lungs showed severe
      diffuse alveolar damage and bronchopneumonia, but no viral inclusion. The spleen
      and lymph nodes revealed lymphoid depletion and the liver showed microvesicular
      steatosis. No specific pathological change was seen in the gastrointestinal tract
      and kidneys. SARS-CoV genome was detected in the nasopharyngeal aspirate and the
      autopsy lung specimen.

PMID- 15490032
TI  - Signet-ring cell carcinoma of the ampulla of Vater.
AB  - Carcinomas of the ampulla of Vater are uncommon, and signet-ring cell carcinoma
      is rare. We report a case of signet-ring cell carcinoma of the ampulla of Vater
      with obstructive jaundice in a 53-year-old man. Abdominal ultrasonography and
      abdominal computed tomographic scan revealed dilatation of the common bile duct,
      intrahepatic duct, and main pancreatic duct, with the obstruction level in the
      distal common bile duct near the ampulla of Vater. Duodenoscopy displayed an
      ampullary tumor protruding from the papilla of Vater with an erythematous and
      sloughing surface. Endoscopic biopsy of the tumor showed a signet-ring cell
      carcinoma. The patient received percutaneous transhepatic cholangiographic
      drainage, and the jaundice gradually improved. A Whipple operation including
      pancreatoduodenectomy and hemigastrectomy was performed. Pathological examination
      confirmed signet-ring cell carcinoma of the ampulla of Vater with direct invasion
      of the periampullary duodenum and distal common bile duct. No gastric lesion or
      nodal metastasis was found. The postoperative course was uneventful. The patient
      was alive with no recurrent disease during a follow-up period of 25 months.

PMID- 15490033
TI  - Russell-Silver syndrome: molecular diagnosis of maternal uniparental disomy of
      chromosome 7 using methylation-specific polymerase chain reaction assay and
      single nucleotide polymorphisms genotyping.
AB  - Russell-Silver syndrome (RSS) should be suspected in patients with prenatal and
      postnatal growth retardation. Because there is no clinical feature specific for
      RSS, molecular analysis is necessary to confirm the diagnosis. Recently, maternal
      uniparental disomy of chromosome 7 (mUPD7) has been reported in approximately 10%
      of RSS patients. We describe a 10-year-old Taiwanese RSS girl with prenatal and
      postnatal growth retardation, relative macrocephaly, a triangular face, frontal
      bossing, and mild fifth finger clinodactyly. Molecular diagnosis of mUPD7 was
      confirmed by use of methylation-specific polymerase chain reaction and haplotype
      analysis with single nucleotide polymorphisms (SNPs) genotyping. Analyzing the
      methylation status of the PEG1/MEST gene is a cost-effective screening method for
      mUPD7 molecular diagnosis. However, positive cases should be subsequently
      confirmed by haplotype analysis using SNPs genotyping or short tandem repeat
      markers.

PMID- 15490034
TI  - Acquired aortic regurgitation after coil occlusion of patent ductus arteriosus.
AB  - Some patients with patent ductus arteriosus (PDA) may develop new aortic
      regurgitation (AR) after coil occlusion. This study evaluated the risk factors
      for the development of AR after coil occlusion of PDA. A total of 23 patients
      with PDA were managed with coil embolization over a three-and-a-half-year period.
      Three patients with pre-embolization AR were excluded. A post-occlusion
      transthoracic echocardiogram was performed within 24 hours after the procedure.
      Ten patients developed AR and 10 did not. Gender, age, weight, body surface area
      (BSA), pulmonary artery pressure, and pulmonary vascular resistance did not
      differ significantly between the 2 groups. Both larger PDA size (either corrected
      for weight or BSA, p = 0.008 and 0.002, respectively) and a higher ratio of
      pulmonary to systemic flow (Qp/Qs) [p = 0.013] were significant risk factors for
      the development of AR after coil occlusion. Re-evaluation of the patients at 3
      and 6 months after the procedure revealed 7 patients still had a regurgitant jet.
      The results of this study suggest that the larger the PDA and larger the shunt,
      the greater the likelihood of developing AR after coil occlusion.

PMID- 15490035
TI  - Medical management of intermittent claudication.
AB  - The symptoms of intermittent claudication (IC) lead sufferers to seek medical
      attention, potentially leading to substantial workup and invasive testing.
      However, only a minority of people with IC develop limb-threatening ischemia or
      symptoms of significant lifestyle-limiting claudication. Patients with IC have a
      substantial risk of concomitant cardiovascular and cerebrovascular disease.
      Assessment of co-morbidities and control of risk factors reduce the
      cardiovascular risk of these patients. A multitude of drugs have been developed
      and tested in numerous trials for the symptoms of IC. Although no drug alone
      offers a "cure" to IC, some are used as adjuvant therapy to reduce claudication
      symptoms.

PMID- 15490036
TI  - Most patients with abdominal aortic aneurysm are not suitable for endovascular
      repair using currently approved bifurcated stent-grafts.
AB  - Strict morphologic criteria must be used for patient selection to achieve durable
      success with endovascular aortic aneurysm repair (EVAR). The goal of this study
      was to assess morphologic suitability (MS) of abdominal aortic aneurysms (AAAs)
      for 2 currently approved bifurcated stent grafts and identify reasons for
      exclusion from EVAR. The authors reviewed the electronic charts of 1,795
      consecutive patients who were diagnosed as having AAA between January 1999 and
      July 2001 at their institution. Three hundred and twenty patients had an AAA with
      a diameter of > or = 5.0 cm, measured on computed tomography (CT). The records of
      301 patients, 254 men, 47 women, with a mean age of 74 years were available for
      review, and these patients constituted the study cohort. Criteria used for MS
      included a proximal neck length > or = 15 mm; neck diameter between 18 and 26 mm;
      neck angulation < or = 60 degrees ; common or external iliac artery (CIA or EIA)
      diameters of 7-16 mm and 8-13 mm, respectively, for AneuRx (Medtronic Ave, Santa
      Rosa, CA) and Ancure (Guidant Cardiac and Vascular Division, Menlo Park, CA)
      bifurcated grafts. AAAs were suitable for AneuRx device in 14% of patients (43 of
      301; 95% CI = 11-19%) and for Ancure in 5% (16 of 301; 95% CI = 3.1-9%). The main
      reason for exclusion was an inadequate proximal aortic neck (73%). The neck was
      too short in 49.5%, too wide in 64% and badly angulated in 12% of the patients.
      Iliac artery morphology precluded EVAR with AneuRx and Ancure devices in 52% and
      80%. Both CIAs were too wide for EVAR in 43% and 77%, respectively. When iliac
      artery diameter < or = 20 mm was accepted, iliac suitability for AneuRx increased
      from 49% to 70% and overall suitability increased from 14% to 20%. When more
      permissive criteria were used for MS (neck length > or = 10 mm, neck diameter <
      or = 30 mm, CIA < or = 20), 39% of patients became candidates for EVAR. More than
      three fourths of the patients with an AAA > or = 5.0 cm in size, seen in a
      tertiary referral center, are morphologically not suitable for EVAR using 2
      currently approved bifurcated endografts. The main reasons for exclusion are a
      short or wide proximal aortic neck. Considerable changes in size of the devices
      and in proximal attachment techniques have to occur before most AAAs will be
      suitable for EVAR.

PMID- 15490037
TI  - Initial experience with endovascular aortic aneurysm repair without cardiologists
      or radiologists--do vascular surgeons really need them?
AB  - Endovascular abdominal aortic aneurysm repair (EVAR) has been predominantly
      accomplished by teams of multidisciplinary interventionalists, frequently under
      the primary direction of cardiologists and radiologists. The purpose of this
      paper was to examine the feasibility and safety of an initial experience of EVARs
      performed by vascular surgeons at a single institution without other
      interventionalists. The authors reviewed the first 50 EVARs performed solely by
      vascular surgeons at our hospital, which we believed represented a fair and
      sizable enough learning curve for this new procedure. The operations were
      performed in an endovascular operating room and the surgeons had prior
      endovascular experience. The EVAR protocol included preoperative abdominal
      computed tomography (CT) scans and aortograms, same-day admissions, epidural
      anesthesia, transfer to the ward the day of surgery, and discharge the first
      postoperative day. CT scans were performed on postoperative day 1 and then
      annually, unless duplex ultrasound (DU) suggested an endoleak. DU was performed 1
      week postoperatively, every 3 months for the first year, and then every 6 months
      thereafter. Of the first 23 patients, 3 required immediate conversion to open
      repair because of device malfunction (all in a Phase III FDA trial) and 1
      underwent conversion 3 weeks after initial graft placement during treatment of a
      failing endograft limb as diagnosed by duplex ultrasonography. None of the next
      27 cases required conversion. In 2 (4%) patients, graft limb occlusions occurred
      postoperatively and were treated with femorofemoral crossover grafts. There were
      5 (10%) endoleaks: 2 were treated endovascularly, 1 closed spontaneously, and 2
      were followed. Several advanced adjunctive endovascular procedures were performed
      concomitantly during EVAR including internal iliac artery coil embolization using
      aortic crossover catheters in 16% (8/50) of patients, proximal or distal
      extension cuff placement in 16% (8/50), and graft limb stenting in 50% (25/50).
      The average length of stay for patients who underwent uncomplicated aortic stent
      grafts was 1.9 days (range, 1-4 days) compared to 2.3 days for all patients
      (range 1-13 days). In no case were other interventionalists necessary for
      intraoperative assistance. These results of EVAR performed solely by vascular
      surgeons are comparable to reports by multidisciplinary teams and support the
      premise that vascular surgeons with endovascular skills have the knowledge and
      capability to begin performing EVAR independently of other specialists.

PMID- 15490038
TI  - Management of juxtarenal aortic aneurysms and occlusive disease with preferential
      suprarenal clamping via a midline transperitoneal incision: technique and
      results.
AB  - Surgical management of juxtarenal aortic (JR-Ao) aneurysms and occlusive disease
      may include supraceliac aortic clamping, a retroperitoneal approach, or medial
      visceral rotation. The authors report their results using preferential direct
      suprarenal aortic clamping via a midline transperitoneal incision. Between July
      1, 1992, and July 31, 2001, they treated 58 patients with JR-Ao disease (44
      aneurysmal, 14 occlusive) via a midline incision without medial visceral
      rotation. Preferential suprarenal aortic clamping was used in 53 cases (42
      proximal to both renal arteries, 11 proximal to the left renal artery only) and
      supraceliac or supramesenteric clamping in 5 cases when there was insufficient
      space for an aortic clamp between the superior mesenteric artery and renal
      arteries. This strategy avoided mesenteric ischemia associated with supraceliac
      clamping in the majority of cases and afforded better exposure of the right renal
      artery than obtainable with a left retroperitoneal approach or medial visceral
      rotation. Eleven patients underwent concomitant renal revascularization. Critical
      adjuncts included the following: (1) selective left renal vein (LRV) division if
      the vein stump pressure was < 35 mm Hg (suggesting sufficient renal venous
      collaterals existed), (2) bilateral renal artery occlusion during aortic clamping
      to prevent thromboembolism, (3) flushing of aortic debris before restoring renal
      perfusion, and (4) routine administration of perioperative intravenous mannitol
      and renal-dose dopamine. Patients with type IV thoracoabdominal aneurysms,
      ruptured aneurysms, or JR-Ao disease approached via a retroperitoneal incision
      (severely obese patients, re-do aortic surgery) were excluded. No patients died
      or required dialysis during their hospital stay. The LRV was divided in 12 (21%)
      cases and reanastomosed in 2 cases (elevated stump pressures). The average
      suprarenal clamp time was 26 minutes (range, 10-60). Postoperative serum
      creatinine remained > 0.5 ng/dL above baseline in 3 (5%) patients. These results
      support suprarenal aortic clamping with a midline transperitoneal incision as the
      optimal strategy for treating juxtarenal aortic aneurysms and occlusive disease.
      The authors believe that selective left renal vein division enhances juxtarenal
      aortic exposure, and routine administration of renal protective agents, along
      with occlusion of both renal arteries during suprarenal aortic clamping, are
      critical adjuncts in performing these operations.

PMID- 15490039
TI  - Vascular reconstruction in limbs with malignant tumors.
AB  - Patients with tumors in limbs who undergo surgical treatment may present
      involvement of major vessels. Major arteries must be reconstructed for limb
      salvage. Major veins may be reconstructed to avoid the onset of venous
      hypertension. The objective of this study is to analyze the results from surgical
      treatment of malignant tumors associated with vascular reconstruction in limbs. A
      prospective follow-up was made of 20 patients with malignant tumors involving
      major vessels in limbs who underwent vascular reconstruction. Arterial and venous
      reconstructions were performed in 11 patients, arterial reconstruction in 7, and
      venous reconstruction in 2. The vascular substitutes utilized were: greater
      saphenous vein (21), expanded polytetrafluoroethylene (ePTFE) prosthesis (5), and
      Dacron prosthesis (5). Vascular complications occurred in 9 patients: 1 rupture
      of the arterial graft, 4 occlusions of the venous graft, and worsening of
      previous edema in 4 patients. Nonvascular complications occurred in 6 patients:
      infection (2), neurologic deficit (2), partial necrosis of the flap (1), and
      enteric fistula (1). Four patients presented local recurrence, and 1 of them
      underwent transfemoral amputation. Seven patients presented pulmonary metastases,
      of whom 4 died. Arterial revascularization in association with the resection of
      limb neoplasm is a safe procedure with a low rate of complications. Venous
      revascularization should be performed using an autologous substitute.

PMID- 15490040
TI  - Factor XIII contrasts the effects of metalloproteinases in human dermal
      fibroblast cultured cells.
AB  - Matrix metalloproteinases (MMPs) are overexpressed in venous leg ulcers,
      determining a breakdown of the main extracellular matrix (ECM) components owing
      mainly to collagenase activities, and so playing a crucial role in ulcer
      pathogenesis. The authors studied the effects of coagulation factor XIII (FXIII),
      which cross-links collagen and other ECM components, in human fibroblast cultured
      cells in the presence and in the absence of matrix metalloproteinases from
      Clostridium histolyticum collagenase. Clostridium collagenase at concentrations
      of 2.0, 1.0, and 0.5 mg/mL was added to normal human dermal fibroblasts cultured
      in the presence of 0.0, 1.0, and 5.0 U/mL of FXIII concentrate (Fibrogammin P,
      Aventis Behring). Cell counting and metabolically active fibroblast evaluation in
      the cultures were monitored for 72 hours, by means of trypan-blue dye and MTT
      test, respectively. The MTT test showed that at the highest collagenase
      concentration (2.0 mg/mL), the cell number decreased more than 95% in 72 hours of
      treatment and no significant differences were observed regardless of the FXIII
      concentrations utilized. At lower collagenase concentration (1.0 mg/mL), in
      absence or in presence of FXIII (1.0 U/mL), the cell number decreased by about
      80% in 72 hours. In contrast, in the presence of higher FXIII levels (5.0 U/mL),
      cells suffered globally significantly less collagenase effects (p = 0.011) and
      the gain was appreciable at each time tested. Finally, at 0.5 mg/mL of
      collagenase concentration, in the absence of FXIII, the cell number decreased by
      about 60% in 72 hours, whereas in presence of FXIII 1.0 U/mL and 5.0 U/mL, cells
      decreased significantly less, by about 35% and 20%, respectively (p < 0.025 and p
      < 0.01, respectively). These data were also confirmed by direct cell counting
      utilizing the trypan-blue test. Factor XIII contrasts effectively the detrimental
      action of Clostridium collagenases in human fibroblast cultured cells. These
      results support several in vivo reports about the effectiveness of its topical
      application in order to enhance the venous ulcer healing processes.

PMID- 15490041
TI  - Endoscopic subfascial perforator vein surgery for patients with severe, chronic
      venous insufficiency.
AB  - Before 1985, surgery on incompetent perforator veins in patients with severe,
      chronic, venous insufficiency and venous ulcerations was generally performed
      utilizing long skin incisions through diseased skin and subcutaneous tissues.
      Known as "the Linton operation," wound infections and poor healing complicated
      this procedure. In 1985 G. Hauer demonstrated a new surgical technique for
      identifying and ligating incompetent perforator veins using an endoscopic
      approach in the limbs' subfascial space. This seminal contribution marked the
      advent of subfascial endoscopic perforator surgery (SEPS). From 1996 to 2003 our
      group prospectively collected data on 86 patients with chronic venous
      insufficiency (CVI) who underwent a SEPS procedure. Preoperative assessment
      consisted of color-flow duplex ultrasound scanning and ascending and descending
      phlebography. The patient's ages ranged from 42 to 82 years (mean 60). A total of
      98 limbs underwent the SEPS procedure from the cohort group of 86 patients. The
      CHEAP classification of the limb disease was used: 45 limbs were classified as
      group C5, 53 limbs group C6. Ninety-eight SEPS procedures were performed without
      significant morbidity on 86 patients. Of the 53 limbs in class C6, 41 had ulcer
      healing within 12 weeks. The remaining 12 limbs in class C6 had ulcer healing
      within 6 months. In this latter group, 9 had ulcers greater than 4 cm in widest
      diameter. These patients underwent a split-thickness skin graft at the time the
      SEPS procedure was performed. The grafts have remained intact after 2 years in
      this cohort group. The results of this study demonstrate that the SEPS procedure
      incorporated into the overall treatment plan for patients with CVI produces
      excellent healing with minimal postoperative complications. The study also
      underscores the important role incompetent perforator veins have in the formation
      of venous ulcers.

PMID- 15490042
TI  - Lower extremity deep venous thrombosis: vascular laboratory quality assurance
      without correlation between ultrasound and venography.
AB  - Venography is rarely available for comparison with ultrasonography (US) as a
      means for quality assurance (QA) in the detection of lower extremity venous
      thrombosis. New QA methods must be implemented. We compared results of multiple
      serial studies performed in the same extremity as a QA indicator. From a 3-year
      sample of close to 9,000 venous tests, we obtained a subset of 44 patients who
      had 331 tests in 71 lower extremities throughout the years. A positive or
      negative study preceded or followed by another positive or negative study was
      considered as a confirmed study. A negative or positive study not preceded or
      followed by a negative or positive study was considered as unconfirmed.
      Explanations were then sought to explain unconfirmed results. There were 169
      (51%) and 124 (37%) confirmed positive and negative studies, respectively, and 13
      (4%) and 25 (8%) unconfirmed positive and negative studies, respectively. Of the
      13 unconfirmed positive tests, 2 were preceded by negative tests, 3 were preceded
      and followed by negative tests, and 8 were followed by negative tests. Of these
      13 tests, 4 documented extensive venous thrombosis. Of the 25 unconfirmed
      negative tests, 11 followed treatment for venous thrombosis, 6 had recurrent
      thrombosis with intermittent lysis, and 8 were followed by positive tests.
      Considering the low probability of extensive thrombosis being a false-positive
      test, positive predictive value was 95% (173/182). Excluding 11 negative tests
      following treatment for venous thrombosis, negative predictive value was 90%
      (124/138) and accuracy was 93% (297/320). US versus US and literature US versus
      venography comparisons of these statistics were similar.

PMID- 15490043
TI  - Maturation and failure rates in a large series of arteriovenous dialysis access
      fistulas.
AB  - The objective of this study was to document maturation and failure rates in a
      large homogeneous series of arteriovenous fistulas (AVFs). Between January 1,
      1996, and December 31, 2001 (60 months), a single surgeon (AFS) in 1 academic
      medical center, constructed 374 AVFs. In this series, all AVFs were developed in
      vessels that had not undergone previous vascular access surgery. Recently, a
      retrospective review of these records revealed that 291 subjects had had complete
      follow-up for at least 3 months, and they constitute the material for this study.
      AVFs were considered a failure if an early occlusion/thrombosis occurred, if in 3
      months the AVF had not matured on clinical examination, or if cannulation in the
      dialysis center was not feasible. A total of 91 AVFs did not mature, for an
      overall failure rate of 31%. An evaluation of failure rates indicated rates in
      females were higher than in males (41% versus 27%). Other risk factors, including
      HIV+ status, hypertension, and diabetes, demonstrated minimal failure differences
      (33%, 31%, and 36%, respectively).

PMID- 15490044
TI  - Duplex ultrasound recognition of spontaneous carotid dissection--a case report
      and review of the literature.
AB  - Spontaneous dissection of the internal carotid artery is an uncommon entity with
      a variable clinical presentation. A high index of suspicion is required to make
      the diagnosis, and prompt diagnosis and treatment with anticoagulation are
      essential for improved patient outcomes. Duplex ultrasound provides a safe and
      reliable imaging modality for early diagnosis and follow-up. The authors present
      a case of spontaneous internal carotid artery dissection with duplex ultrasound
      findings and a review of the literature.

PMID- 15490045
TI  - Celiomesenteric trunk compression and absence of collateral vessels in the large
      intestine--a case report.
AB  - The authors report the case of a rare mesenteric anomaly in a 71-year-old man who
      presented with a preexisting abdominal aortic aneurysm (AAA) and a progressive
      history of postprandial abdominal pain and 10-lb weight loss. Aortography
      revealed a common celiomesenteric trunk, an absent middle colic artery, and a
      stenotic inferior mesenteric artery. At operation, neural fibers compressing the
      common celiomesenteric trunk were lysed, the AAA was repaired, and the inferior
      mesenteric artery was subjected to endarterectomy and then reimplanted. The
      patient remains well and free of symptoms 1 year after operation. This rare case
      demonstrates the many different causes of intestinal angina and its surgical
      relief.

PMID- 15490046
TI  - Splenic artery-to-superior mesenteric artery bypass for chronic mesenteric
      ischemia--a case report.
AB  - Chronic mesenteric ischemia (CMI) is a serious vascular condition that if left
      untreated may progress to acute ischemia resulting in bowel necrosis and high
      surgical morbidity/mortality rates. Elective intervention has been shown to
      prevent this progression and relieve symptoms. Current open surgical intervention
      involves arterial bypass using a vein or synthetic graft conduit with the inflow
      originating from the aorta or iliac artery. In some circumstances, the splenic
      artery provides an additional treatment option for revascularization of the
      superior mesenteric artery. In certain cases, the splenic artery has several
      advantages over traditional surgical options. The splenic artery is an arterial
      conduit much like the internal mammary artery used in coronary artery bypass
      grafting. These grafts are known for their long-term patency and in selected
      clinical circumstances are preferred over venous grafts. Because the splenic
      artery has a natural inflow, only a single vascular anastomosis at the outflow
      vessel (the SMA) is necessary. This lessens the risk of anastomotic stenosis by
      decreasing the number of anastomoses created and it makes the procedure shorter
      in duration. The fact that the inflow is provided by the splenic artery makes
      cross-clamping of the aorta unnecessary, thereby lessening the risk of producing
      cardiac ischemia and declamping hypotension. A disadvantage is the risk of
      splenic ischemia with the possible need for splenectomy. The majority of
      individuals will have adequate collateral supply to the spleen via the short
      gastric arteries. The risk to the patient of splenectomy versus the benefits of a
      less complicated arterial reconstruction with avoidance of aortic cross-clamping
      must be weighed on a case-by-case basis. Preventing the progression to acute
      mesenteric ischemia with its increased mortality by timely restoration of
      adequate vascular supply is an important principle in treating patients with CMI.
      Controversy still exists over the best treatment option for these patients,
      whether it be antegrade versus retrograde bypass, single-vessel versus
      multivessel reconstruction, or open surgical repair versus endovascular
      intervention. In selected patients, the use of the splenic artery can be
      considered as an additional option for arterial reconstruction of the SMA.

PMID- 15490047
TI  - Surgical intervention for isolated dissecting aneurysm of the superior mesenteric
      artery--a case report.
AB  - A 44-year-old man with abdominal pain was diagnosed as having a spontaneous
      isolated dissection of the superior mesenteric artery. The patient was
      successfully treated with endoaneurysmorrhaphy 5 months after the onset and has
      been symptom free 15 months after surgery. In view of the excellent surgical
      outcome in the literature, surgical intervention for this rare pathology should
      be considered.

PMID- 15490048
TI  - Endovascular management of traumatic axillary artery dissection--a case report
      and review of the literature.
AB  - A 43-year-old man was admitted to this hospital with a cool, slightly numb, left
      upper extremity after trauma. Physical examination revealed a cool left forearm
      and hand, with no distal pulses. An intraoperative angiogram demonstrated short
      segment dissection and occlusion of the left axillary artery. A 10 mm x 40 mm
      self-expanding stent was placed across the intimal flap to reinstitute peripheral
      flow. Early postoperative duplex scanning showed normal flow through the axillary
      artery.

PMID- 15490049
TI  - Carotid blowout with infection: management with endovascular and open vascular
      approaches--a case report.
AB  - The management of patients with head and neck cancer can be complicated by
      massive carotid artery hemorrhage, often requiring ligation owing to the emergent
      conditions and scarring from previous surgery and radiation. A case of emergent
      endovascular management of carotid artery hemorrhage in a patient treated for
      pharyngeal carcinoma is described. Hemorrhage was controlled, but on follow-up
      the patient developed a carotid-cutaneous fistula with exposure of the coils.
      Further management required the use of autogenous vein to replace the involved
      vessels. This case demonstrates that endovascular control of carotid hemorrhage
      can be successful, but close follow-up is necessary to identify potential
      subsequent complications.

PMID- 15490050
TI  - Detection of asymptomatic differentiated thyroid carcinoma by neck
      ultrasonographic screening for familial nonmedullary thyroid carcinoma.
AB  - Mass screening for the purpose of detecting thyroid cancer at its earliest stage
      may not be recommended at the present time, but screening focused on certain risk
      groups is advocated. Familial nonmedullary thyroid carcinoma (FNMTC) is a
      distinct clinical entity with a high incidence of multifocality and association
      with multiple benign nodules. FNMTC patients have shorter disease-free survival
      than do sporadic disease patients because of frequent locoregional recurrence.
      Screening by neck ultrasonography was performed for symptom-free family members
      of patients with FNMTC. A total of 149 subjects representing 53 FNMTC families
      were examined in this study. The average age of the patients was 41.0+/-19.0
      years (range 3-76 years) with a female/male ratio of 104:45. At least one thyroid
      nodule was found in 77 (51.7%) of the 149 patients. Surgery was performed in 18
      patients, and thyroid cancer was discovered in 15 of them (10.1%; 14 women, 1
      man; 32-61 years of age). Papillary thyroid cancer (PTC) was found in 14 and
      follicular thyroid cancer combined with PTC in 1. The tumors averaged 9.1+/-5.4
      mm (3-21 mm) in greatest diameter. Intraglandular metastases were found in 7
      (47%) of the 15 patients with thyroid cancer. Lymph node metastases were found in
      6 (43%). Ultrasonographic screening for FNMTC family members may enable the
      discovery of asymptomatic thyroid cancer. Because of the high incidence of
      intraglandular and lymph node metastases, we recommend screening with
      ultrasonography for early detection in family members of patients with FNMTC.

PMID- 15490051
TI  - Primary hyperparathyroidism in the young age group: particularities of diagnostic
      and therapeutic schemes.
AB  - Primary hyperparathyroidism (pHPT) is a rare endocrine disease in children and
      young adults. The widespread use of new developments in pHPT surgery (i.e.,
      unilateral and minimally invasive approaches) is based on the assumption that the
      solitary adenoma is the predominant intraoperative finding, but it has not been
      evaluated in the subgroup of young patients. From April 1986 to December 2002, a
      total of 1219 patients with pHPT have been operated on in our institution. The
      records of 64 patients (5.3%) younger than 30 years were extracted and compared
      to those of the older patients. The study group (median age 25 years, range 11-30
      years) had significantly less bone pain, fewer signs of bone demineralization,
      and fewer neuropsychiatric symptoms. Eleven patients had hereditary disease. We
      found a solitary adenoma in only 32 of the 64 juvenile patients (p < 0.001),
      multiple gland disease in 25 patients (p < 0.001), and two suspected carcinomas.
      No adenoma could be identified in five patients. Follow-up of 54 patients after a
      median of 6.1 years revealed 42 normocalcemic patients, 5 hypocalcemic patients,
      and 7 patients with hypercalcemia. Altogether, 16 juvenile patients underwent
      parathyroid reoperations (25%) compared to 105 older patients (9%) (p = 0.003).
      Problems and difficulties with parathyroid surgery are pronounced in younger
      patients. The high rate of multiple gland disease requires bilateral cervical
      exploration as the standard procedure in pHPT patients younger than 30 years of
      age.

PMID- 15490052
TI  - Are there significant benefits of minimally invasive endoscopic thyroidectomy?
AB  - Minimally invasive surgery using endoscopic vision is widely employed for the
      treatment of thyroid diseases. We have performed endoscopic thyroidectomy by the
      axillary approach (axillary approach) and video-assisted thyroidectomy via a 3 cm
      cervical incision (video-assisted approach). In this study, we evaluated the
      efficacy of these two procedures. Each procedure was performed in 20 consecutive
      consenting patients. The degree of invasiveness after surgery was compared using
      postoperative results. The amount of pain and satisfaction with surgery was
      evaluated by grade (1-5) using a patient questionnaire. All thyroidectomies were
      completed successfully. No recurrent laryngeal nerve palsies occurred. Operating
      time for the video-assisted approach was significantly shorter than that for the
      axillary approach (p < 0.01). The amount of pain for the axillary approach on 1,
      3, and 5 days after operation, respectively, was graded 3.2+/-0.7, 2.1+/-0.6, and
      1.6+/-0.7 compared to 2.7+/-1.1, 1.7+/-0.7, and 1.1+/-0.2 for the video-assisted
      approach. The postoperative course was significantly less painful in patients
      undergoing the video-assisted approach on postoperative days 3 and 5 (p < 0.01).
      The degrees of satisfaction for the axillary approach and the video-assisted
      procedure were 1.2+/-0.4 and 2.4+/-1.0, respectively (p < 0.01). The video
      assisted approach is less "invasive" than the axillary approach, but the axillary
      approach may be indicated for patients who are anxious about the visible cosmetic
      results.

PMID- 15490053
TI  - Papillary microcarcinoma of the thyroid: how should it be treated?
AB  - We previously demonstrated that (1) most papillary microcarcinomas can be
      followed without surgical treatment and (2) when surgery is performed, patients
      with lateral lymph node metastasis detected on preoperative ultrasonography (US)
      are more likely to develop recurrence. In this study, we further investigated the
      application of these strategies. To date, we have observed 211 patients (average
      follow-up 47.9 months). In more than 70% of these patients the tumor size did not
      increase during the follow-up period. There were no clinicopathologic features
      linked to tumor enlargement except in tumors > or = 7 mm, which tended to enlarge
      in patients followed for 4 years. To evaluate not only whether observation can
      continue but also how to dissect the lymph nodes optimally at surgery, US
      diagnosis for lateral node metastasis is essential because the presence of US
      diagnosed lateral metastasis is an even stronger predictive marker for recurrence
      than the presence of pathologically confirmed node metastasis. The positive
      predictive value (PPV) was 80.6% for US but reached 100% if fine-needle
      aspiration biopsy (FNAB) of nodes or FNAB-thyroglobulin measurement is added.
      Furthermore, carcinomas occupying the upper region of the thyroid more frequently
      showed US-diagnosed and pathologically confirmed lateral metastasis, and those
      measuring > or = 7 mm were more likely to show pathologically confirmed lateral
      metastasis. These findings suggest that, for papillary microcarcinoma: (1) US
      diagnosed lateral metastasis is a strong marker predicting a worse relapse-free
      survival; (2) FNAB of nodes and FNAB-thyroglobulin measurement are useful tools
      for evaluating lymph node metastasis; and (3) careful US evaluation for lateral
      metastasis is necessary in patients with a tumor measuring > or = 7 mm or that is
      located in the upper region of the thyroid both during observation and
      preoperatively.

PMID- 15490054
TI  - Preoperative neck ultrasonographic mapping for persistent/recurrent papillary
      thyroid cancer.
AB  - Surgical resection of persistent/recurrent (P/R) papillary thyroid cancer (PTC),
      when localized to the neck, is generally recommended; however, its impact on the
      course of the disease is not clear. We introduced a new technique in the form of
      preoperative neck ultrasonographic mapping (US-M) to improve the outcome of the
      surgical resection of P/R PTC. A total of 19 patients had undergone regional
      (central, lateral, or both) neck dissection before introducing the current
      technique (group 1, or G1), and 26 patients (group 2, or G2) had limited lymph
      node resection guided by US-M with findings accurately plotted on a standard
      diagram. All of the operations were performed by a single surgeon. The surgical
      outcomes of the two groups were compared. The resected lesions were positive for
      PTC in 17 patients (89.5%) in G1 and in 25 patients (96.2%) in G2. In G2, the
      intraoperative findings exactly matched the US-M in 23 patients (88.5%).
      Postoperatively, neck US became negative in 50% in G1 and in 83.3% in G2 (p =
      0.02). Thyroglobulin (Tg) became undetectable in 37.5% in G1 and 52.3% in G2 (p =
      0.37). Whole-body iodine scans (WBS) became negative in one of six patients
      (16.7%) in G1, and in three of four patients (75%) in G2, (p = 0.06). After a
      mean follow-up of 23.8+/-7.1 months in G1 and 9.8+/-4.7 months in G2, 6 patients
      (31.6%) in G1 and 15 patients (62.5%) in G2 were in remission (p = 0.04), whereas
      the disease persisted in 13 cases (68.4%) in G1 and 9 (37.5%) in G2 (p = 0.04).
      In conclusion, US-M improved the surgical outcome, as evidenced by the
      postoperative US, Tg, and WBS findings and the higher remission rate for the G2
      patients than for the G1 patients.

PMID- 15490055
TI  - Predictive factors for recurrence from a series of 74 children and adolescents
      with differentiated thyroid cancer.
AB  - The influence of clinical and treatment factors on the risk of recurrence was
      analyzed from a retrospective series of 74 children and adolescents with thyroid
      cancer (55 girls, 19 boys; age 2-20 years). Two groups, comparable in terms of
      age, sex, and previous radiotherapy, were compared according to the presence
      (group 1) or absence (group 2) of cervical lymph nodes identified by palpation or
      ultrasonography. Total thyroidectomy (TT) with lymph node dissection (LND) was
      performed in the 19 group 1 patients, whereas in group 2 patients (n = 55)
      lobectomy was performed in 29, TT in 26, and LND in 7. Pathology studies showed
      papillary thyroid carcinoma in 95% of cases. In group 1, tumors were more
      frequently multifocal (89% vs. 16% in group 2), invasive with extension beyond
      the thyroid capsule (68% vs. 5% in group 2), and of the diffuse sclerosing
      variety (63% vs. 4% in group 2) (p < 0.001). With a median follow-up of 61
      months, lymph node recurrence was seen in 53% of group 1 patients and in no
      patients in group 2. Three group 2 patients (10%) were reoperated for a local
      recurrence after lobectomy. Risk factors for reintervention were young age (< 15
      years) (p < 0.01) and cervical lymph nodes (p < 0.001). Survivals without
      reintervention at 5 and 10 years were, respectively, 58% and 38% for group 1 and
      94% and 90% for group 2 (p < 0.001). At the time of analysis, 68% of group 1
      patients and 98% of group 2 patients were in remission. In conclusion, the
      presence of palpable cervical lymph nodes at diagnosis is associated with more
      invasive forms of malignancy and is a predictive factor of recurrence regardless
      of the extent of the initial surgery.

PMID- 15490056
TI  - Reasons for conversion from laparoscopic to open or hand-assisted adrenalectomy:
      review of 261 laparoscopic adrenalectomies from 1993 to 2003.
AB  - Over the past decade, laparoscopic adrenalectomy has become the operation of
      choice for resecting adrenal tumors. However, few reported data exist regarding
      the reasons for conversion from laparoscopic to open or hand-assisted
      adrenalectomy. We retrospectively reviewed the records of 261 consecutive
      laparoscopic adrenalectomies performed by one surgeon between 1993 and 2003.
      Laparoscopic adrenalectomy could not be completed in 8 of the 261 patients (3%);
      four of the operations were converted to hand-assisted laparoscopic adrenalectomy
      and four to open adrenalectomy. The reasons for the conversion were as follows:
      In three patients the tumor was too adherent to surrounding structures to be
      resected laparoscopically; in three patients the tumor was found to have
      malignant features during laparoscopy, and the operation was converted to achieve
      proper resection margins; in two patients the tumors were too large (15 and 16
      cm, respectively) to be safely removed laparoscopically. The eight resected
      tumors included three pheochromocytomas, one myelolipoma, one angiomyolipoma, one
      solitary fibrous tumor, one liposarcoma, and one metastatic hepatocellular
      carcinoma. There were no cases in which conversion was required emergently for
      bleeding or other intraoperative catastrophes. All eight of the tumors removed
      were at least 5 cm in size (range 5-16 cm). The mean length of hospitalization
      was 4.4 days (range 3-8 days).

PMID- 15490057
TI  - Trends in utilization of adrenalectomy in the United States: have indications
      changed?
AB  - Minimally invasive approaches have dramatically reduced morbidity associated with
      adrenalectomy. There has been concern that an increased frequency of adrenal
      imaging along with the advantages of less morbidity could influence the
      indications for adrenalectomy. We tested the hypothesis that adrenalectomy has
      become more common over time and that benign diseases have been increasingly
      represented among procedural indications. The Nationwide Inpatient Sample (NIS)
      database was utilized to determine the incidence of adrenalectomy and the
      associated surgical indications in the United States between 1988 and 2000. All
      discharged patients were identified whose primary ICD-9-CM procedure code was for
      adrenalectomy, regardless of the specific surgical approach (laparoscopic
      adrenalectomy was not reliably coded). This subset was then queried for
      associated ICD-9-CM diagnostic codes. Linear regression and t-tests were utilized
      to determine the significance of trends. The total number of adrenalectomies
      increased significantly, from 12.9 per 100,000 discharges in 1988 to 18.5 per
      100,000 discharges in 2000 (p = 0.000003). The total number of adrenalectomies
      with a primary ICD-9-CM code for malignant adrenal neoplasm did not increase
      significantly: from 1.2 per 100,000 discharges in 1988 to 1.6 per 100,000
      discharges in 2000 (p = 0.47). The total number of adrenalectomies with a primary
      ICD-9-CM diagnostic code for benign adrenal neoplasm increased significantly,
      from 2.8 per 100,000 discharges in 1988 to 4.8 per 100,000 discharges in 2000 (p
      = 0.00002). The average percentage of adrenalectomies performed for malignant
      neoplasm was significantly higher during the period 1988--1993 when compared to
      1994--2000 (11% vs. 9%; p = 0.002). The average percentage of adrenalectomies
      performed for benign neoplasm was significantly lower during 1988--1993 when
      compared to 1994--2000 (25% vs. 28%; p = 0.015). Adrenalectomy is being performed
      with increasing frequency. This is associated with an increase in the proportion
      of adrenalectomies performed for benign neoplasms. Assuming no significant change
      in disease prevalence during the study period, these data suggest that
      indications for adrenalectomy may have changed somewhat over that period.

PMID- 15490058
TI  - Long-term survival of patients with small intestinal carcinoid tumors.
AB  - Midgut carcinoid tumors are rare and have a markedly better prognosis than
      adenocarcinoma in the small intestine. New diagnostic methods and medical as well
      as surgical therapies have evolved during the last decades, leading to more
      active care of these patients. Patients with small intestinal carcinoids
      diagnosed from 1960 to 2000 in the duodenum (n = 89) and jejunum/ileum (n = 2437)
      were identified in the Swedish Cancer Registry. Cases without histologic
      verification and autopsy cases were excluded. Overall, cause-specific and
      relative survival were calculated. The overall 5-, 10-, and 15 year survivals
      were, respectively, 60%, 46%, and 28% for duodenal tumors and 56%, 36%, and 23%
      for jejunal/ileal tumors. Cause-specific 5-, 10-, and 15-year survival was 94%
      for all three follow-up periods for duodenal tumors and 87%, 80%, and 77% for
      those in the jejunum/ileum. The corresponding relative survivals were,
      respectively, 72%, 67%, and 51% for duodenal tumors and 67%, 54%, and 44% for
      those in the jejunum/ileum. Sex did not influence overall or cause-specific
      survival. The age at diagnosis correlated inversely with overall and cause
      specific survival for tumors in the jejunum/ileum. For tumors in the
      jejunum/ileum, the overall and cause-specific survival correlated with the time
      period of diagnosis, with a more favorable prognosis for those diagnosed in
      recent years. A multivariate Cox proportional hazards model showed similar
      results. We concluded that young age and diagnosis in recent years are positive
      predictors of survival for patients with midgut carcinoids. The divergence
      between cause-specific and relative survival implies the need for a more detailed
      analysis of the causes of death of these patients.

PMID- 15490059
TI  - Risk factors for recurrent nodular goiter after thyroidectomy for benign disease:
      case-control study of 244 patients.
AB  - Surgery for recurrent nodular goiter is associated with a significant risk of
      parathyroid and recurrent laryngeal nerve (RLN) morbidity. Total thyroidectomy
      for benign disease is assessed. The aim of this study was to evaluate the risk
      factors for recurrence and the morbidity associated with reoperation. From 1969
      to 1996 a total of 4334 thyroidectomies were performed, of which 122 were for
      recurrent nodular goiter (group I: 116 women, 6 men). A matched case-control
      study of 122 patients operated on for nonrecurrent multinodular goiter was
      performed (group II: 112 women, 10 men). Age, family history, initial surgery,
      pathology, and morbidity were compared in the two groups by chi2 test, Fisher's
      exact test, and the Mantel-Haenszel test. The mean age was 39.88 years in group I
      and 47.89 years in group II. There was no statistical difference in relation to
      the extent of thyroidectomy or morbidity after initial surgery. Statistical
      differences were identified regarding age (p = 0.000002) and the multinodular
      nature of the initial goiter (p = 0.005). Bilaterality and family history were
      less significant (p = 0.09 andp = 0.08, respectively). Temporary RLN palsy and
      temporary hypoparathyroidism were higher in group I (12.3% vs. 5.7%,p = 0.0737;
      10.6% vs. 1.7%, p = 0.00337). Permanent RLN palsy was found in 0.8% in group I
      and in none in group II (p = 0.5, NS). Young age and multiple nodules at initial
      surgery are risk factors for recurrence. A higher rate of temporary morbidity was
      demonstrated after surgery for recurrent goiter. Total thyroidectomy for
      multinodular goiter is advisable.

PMID- 15490060
TI  - 131I-meta-iodobenzylguanidine in the management of metastatic midgut carcinoid
      tumors.
AB  - The management of metastatic neuroendocrine tumors incorporates multimodal
      therapy with surgery, biotherapy, and chemotherapy. Tumor-targeted therapies
      using radiolabeled octreotide and metaiodobenzylguanidine (mIBG) represent a
      novel treatment approach. The aim of this study was to evaluate the effectiveness
      of 131I-mIBG in the treatment of metastatic midgut carcinoid tumors. survival
      outcomes were assessed for patients treated at two regional cancer centers and
      then compared. One center used 131I-mIBG routinely in the management of
      metastatic carcinoid tumors (center A), and the other did not use this modality
      (center B). Only patients with histologically proven metastatic carcinoid tumor
      shown, or thought most likely, to be of midgut origin were included in the study.
      During the period 1980 to 2002, a series of 58 patients from center A with
      metastatic carcinoid tumor arising from the midgut underwent multimodality
      therapy with the addition of 131I-mIBG. Their median age was 64 years. The median
      dose of 131I-mIBG administered was 6751 MBq, and there was an average of 2.8
      treatments per patient. During the same period, 58 patients with metastatic
      carcinoid were treated at center B with similar multimodality therapy without the
      use of 131I-mIBG therapy. Their median age was 65 years. Survivals at 3 and 5
      years were 77% and 63%, respectively (95% CI 47-75), for group A. The 3- and 5
      year survivals for group B were 56% and 47% (95% CI 34-59), respectively. The
      mean follow-up was 6.6 years for group A and 5.0 years for group B. Although
      retrospective in nature, this study suggests that the addition of 131I-mIBG
      therapy to the treatment protocol of patients with metastatic midgut carcinoid
      tumors prolongs survival.

PMID- 15490061
TI  - Surgical management of amiodarone-associated thyrotoxicosis: Mayo Clinic
      experience.
AB  - Amiodarone-associated thyrotoxicosis (AAT) is often poorly tolerated owing to
      underlying cardiac disease, and it is frequently refractory to conventional
      medical treatment. The goal of this study was to describe the patient
      characteristics, management, and outcomes of all the patients treated surgically
      for AAT at a single institution. We conducted a retrospective chart review of all
      patients managed surgically for AAT (April 1985 through November 2002) at the
      Mayo Clinic in Rochester, Minnesota. Altogether, 29 men and 5 women, ages 39 to
      85 years (median 60 years), treated with amiodarone for 3 to 108 months underwent
      near-total or total thyroidectomy. Frequent symptoms were worsening heart
      failure, fatigue, weight loss, and tremor. Altogether, 12 patients failed medical
      management of their AAT, and 21 received no preoperative medical therapy. One
      patient had been successfully managed medically but required definitive
      treatment. Common indications for operation were the need to remain on
      amiodarone, cardiac decompensation, medically refractory disease, and severe
      symptoms, both hyperthyroid and cardiac, necessitating prompt resolution. The
      median+/-SD American Society of Anesthesiologists (ASA) classification (1 =
      healthy through 5 = moribund) was 3.00+/-0.58. A total of 27 specimens had
      histology consistent with AAT. Complications included death (n = 3),
      rehospitalization (n = 3), symptomatic hypocalcemia (n = 2), pneumonia (n = 2),
      cervical hematoma (n = 1), prolonged ventilatorywean (n = 1), and stroke (n = 1);
      one patient developed hypotension, adult respiratory distress syndrome, and
      sepsis. Of the 31 surviving patients, 25 (80%) remained on amiodarone
      postoperatively. The median follow-up was 29 months, at which time all surviving
      patients were free of hyperthyroid symptoms. Thyroidectomy is an effective
      treatment for AAT but has a high incidence of perioperative morbidity and
      mortality. The cardiovascular co-morbidities and high operative risk in this
      group of patients may account for the increased complication rate.

PMID- 15490062
TI  - Fine needle aspiration and intraparathyroid intact parathyroid hormone
      measurement for reoperative parathyroid surgery.
AB  - Some authors have praised the value of fine needle aspiration (FNA) with
      measurement of intraparathyroid intact parathyroid hormone (iPTH) for
      localization of the hypersecreting gland(s) in recurrent or persistent primary
      hyperparathyroidism (HPT). The aim of the present study was to determinate
      whether FNA for iPTH assay is an effective procedure to distinguish between
      normal and hypersecreting parathyroid glands. We performed a prospective study of
      170 patients who underwent cervicotomy. They were divided into three groups:
      group A, 50 patients with thyroid diseases; group B, 100 patients with primary
      HPT; group C, 20 patients with secondary HPT. We performed intraoperative FNA for
      iPTH measurement from the thyroid, and from the normal and enlarged parathyroid
      glands, and we compared the different intraglandular iPTH assays. In group A, the
      intraparathyroid iPTH level was < 1000 pg/ml in 68% of the patients. In group B,
      in the pathological parathyroid gland iPTH was > 1000 in 88%; conversely, in the
      normal adjacent parathyroid glands it was < 1000 in 79%. In group C,
      intraparathyroid iPTH of enlarged glands was > 1000 in 80%. Intrathyroid iPTH was
      < 100 pg/ml in 96% for the three groups. We conclude that FNA for intraglandular
      iPTH measurement is an effective tool for distinguishing between normal and
      pathological parathyroid glands in the setting of primary HPT (p < 0.05), and
      between thyroid and parathyroid glands in groups A and B. But the procedure
      should be carried out in conjunction with the sestamibi scan and ultrasonography
      before surgical reintervention.

PMID- 15490063
TI  - Bone mineral density in menopausal women with primary hyperparathyroidism before
      and after parathyroidectomy.
AB  - The relationship between osteoporosis and primary hyperparathyroidism (pHPT) has
      not been definitely established because both diseases occur predominantly in
      postmenopausal women, and because PTH has a paradoxical effect on bone. We have
      investigated the prevalence of reduced bone mineral density (BMD) in women with
      pHPT, its relationship with metabolic parameters, and its course after
      parathyroidectomy. A prospective observational study was carried out on
      perimenopausal and postmenopausal women consecutively diagnosed and operated on
      for pHPT. Demographic data were recorded, as well as, PTH, Ca, calciuria/24h, P,
      vitamin D, adenoma weight. The BMD was measured at three sites: femoral neck
      (FN), proximal femur (PF), and lumbar spine (LS). Fifty-two patients were
      included with a mean age of 61+/-12 years. The prevalence of reduced BMD (< or =
      1SD, T-score) was 80%-100% depending on site. Parathyroid hormone was higher in
      patients with osteoporosis (319+/-181 pg/ml) than in those with osteopenia (230+/
      83 pg/ml) or normal BMD (148+/-81 pg/ml;p < 0,04). Twenty-eight patients were
      investigated 1 year after parathyroidectomy. The BMD improved significantly at
      all sites, particularly in patients with osteoporosis. Age correlated inversely
      with BMD increases at the femoral sites (r= -0,47;p = 0,02) but not at the LS. 25
      OHD3 plasma levels correlated inversely with BMD increases at PF (r= -0,76; p <
      0,0001). In pHPT, there is a high prevalence of BMD abnormalities. No metabolic
      variables had a definite influence on BMD values but a tendency was observed for
      lower BMD in severe pHPT. One year after parathyroidectomy, there were
      significant BMD increases that were more marked at femoral sites, in younger
      patients, in patients with preoperative osteoporosis, and in those with lower
      plasma levels of 25-OHD3.

PMID- 15490064
TI  - Clinical analysis of thyroid cancer in adult patients exposed to ionizing
      radiation due to the Chernobyl nuclear accident: 5-year comparative
      investigations based on the results of surgical treatment.
AB  - The aim of study was to compare clinical and pathologic findings of surgically
      removed thyroid tumors in adults with or without history of irradiation due to
      the Chernobyl accident. From 1990 to 2003, 2363 adults with no evidence of
      radiation influence in their history (group A) have undergone operation for
      thyroid nodules. During the same period, 311 patients (born before 1969) with
      strict evidence of Chernobyl irradiation also underwent operation (group B). Both
      groups were similar in age, sex, and preoperative examination. Group B
      represented three of the four official categories of people affected by the
      Chernobyl accident: 1-recovery operation workers; 2-people evacuated from the
      restricted area; 3-inhabitants of contaminated areas. The rate of thyroid
      carcinoma among all cases of thyroid nodules was significantly higher in group B-
      32.8% (102 patients) versus 27.2% (644 patients) in group A (p < 0.05). But a
      more distinct difference was observed in 1 and 2 categories of group B patients
      (the rate of cancer was, correspondingly, 54.8% and 47.8%;p < 0.01). The
      percentage of the invasive form of cancer (T4) was significantly higher in
      irradiated patients-39% versus 23% (p < 0.05) as were regional metastases
      (N1a,1b)--41% versus 19% (p < 0.01) and frequency of multifocality (33% versus
      24%; p < 0.05). The most distinguished features were found in 1 category of group
      B: T4--in 47%, N1a-1b--in 62%, multifocality--in 41%. Our results suggest the
      irradiation as a cause of thyroid cancer in adult victims of Chernobyl and
      confirm the increasing aggressiveness of such tumors.

PMID- 15490065
TI  - Multiple endocrine neoplasia type 1 parathyroid adenoma development over time.
AB  - Multiple gland parathyroid disease is one of the hallmarks of multiple endocrine
      neoplasia (MEN) type 1. Often mislabeled parathyroid hyperplasia, the process is
      actually the development of multiple adenomas. Some clinicians have reported
      results of selective parathyroidectomy in this group, removing only grossly
      enlarged glands. We argue that all the glands are at risk and should be addressed
      at any planned parathyroid intervention. Our hypothesis is that, given sufficient
      time, patients would all develop adenomas in each of the parathyroid glands. Our
      available data to address this issue are the parathyroidectomy results from a
      single institution series. Patients who had initial parathyroid exploration for
      hyperparathyroidism in the setting of MEN-1 were reviewed. This study includes
      those patients who had the weights of the resected glands documented; 23 men and
      21 women met the criteria. The total weight of the parathyroid glands did not
      vary with the age of the patient at operation. However, the number of normal
      glands identified did vary significantly with age (p < 0.02), with older patients
      being less likely to have any normal parathyroid glands. Although total
      parathyroid weight may correlate with development of hypercalcemia and
      indications for operation, the involvement of multiple parathyroid glands in MEN
      1 is a function of time, as independent events in each gland must occur. Given
      time, MEN-1 patients all develop multiple gland disease, and this reality must be
      used in planning operative management for patients with this syndrome.

PMID- 15490066
TI  - Does robotic adrenalectomy improve patient quality of life when compared to
      laparoscopic adrenalectomy?
AB  - The purpose of this study was to evaluate and compare perioperative quality of
      life in patients after laparoscopic versus robotic adrenalectomy. From November
      2000 through August 2003, 33 consecutive patients underwent laparoscopic (n = 14)
      and robotic (n = 19) adrenalectomy. Data were obtained prospectively during
      management and by patient questionnaire (SF36, State-Trait Anxiety Inventory)
      preoperatively and postoperatively, at day 4 and at 6 weeks. Physical
      functioning, role limitations due to physical health problems, and bodily pain
      (Physical SF36 scores) were decreased at day 4 (p = 0.004) in all patients when
      compared to preoperative levels; and became similar to preoperative levels after
      6 weeks. Patients who underwent robotic adrenalectomy had an increased score at 6
      weeks of role limitations due to emotional problems (Mental SF36 score) (p =
      0.03). No other significant difference was observed between patients after
      laparoscopic or robotic adrenalectomy. Although state anxiety was decreased
      postoperatively at day 4 and at 6 weeks (p = 0.01) in all patients, there was no
      significant difference between laparoscopic and robotic adrenalectomy.
      Postoperative pain was similar in both groups but had a tendency to be higher
      when patients underwent a left adrenalectomy (p = 0.07). Similarly, state anxiety
      had a tendency to be higher postoperatively at day 4 in patients after left
      adrenalectomies (p = 0.06). This study provides an evaluation of perioperative
      quality of life in patients after minimally invasive (laparoscopic and/or
      robotic) adrenalectomy. We observed no major difference between patients who
      underwent laparoscopic or robotic adrenalectomy. Thus, patients' perioperative
      quality of life is not a justifiable parameter on which to base promotion of
      robotic adrenalectomies.

PMID- 15490067
TI  - Accuracy of surgeon-performed ultrasound in parathyroid localization.
AB  - Ultrasound is one of the preferred modalities for localization of abnormal
      parathyroids. Accuracy of ultrasound is technician-dependent. This study was
      undertaken to determine the accuracy of surgeon-performed ultrasound (SPU) for
      the localization of parathyroid tumors in comparison to radiology-performed
      ultrasound (RPU) and nuclear scintigraphy (NS). In this series 74 consecutive
      patients with untreated primary hyperparathyroidism underwent SPU at the initial
      clinic visit; 21 of these patients did not undergo surgery and are excluded from
      the analysis. Of the 53 patients remaining, RPU was obtained in 26, and 52
      patients underwent NS. Directed parathyroidectomy was performed with use of the
      intraoperative parathyroid hormone assay (IOPTH). In all, 46 patients had a
      single adenoma as indicated by IOPTH and final pathology. Two patients had double
      gland disease, and 5 patients had multi-gland hyperplasia. The sensitivity of SPU
      was 82% and the specificity was 90% in detecting the diseased glands on the
      correct side (right versus left). The sensitivity for RPU was 42% and the
      specificity was 92% (n = 26). The sensitivity of NS was 44% and the specificity
      was 98% (n = 52). In only one case did RPU or NS detect a gland not found by SPU.
      SPU can be done with accuracy comparable to other ultrasound series in the
      literature, and it may be superior to RPU or NS in some institutions. It is
      important for surgeons to be aware of local institutional expertise when relying
      on RPU and NS during preoperative evaluation prior to directed parathyroidectomy.

PMID- 15490068
TI  - Sestamibi scan-directed parathyroid surgery: potentially high failure rate
      without measurement of intraoperative parathyroid hormone.
AB  - The present study evaluated sestamibi scan-directed parathyroidectomy with
      intraoperative parathyroid hormone (PTH) assessment (ioPTH). The preoperative
      sestamibi scintigraphies were compared with the intraoperative findings for 103
      patients undergoing first exploration for sporadic primary hyperparathyroidism
      (pHPT). Data were collected prospectively. Ninety-nine patients (96%) were cured.
      Patients with persistent pHPT (n = 4) all had an incorrect scintigram as well as
      an insufficient decline of ioPTH. At operation, 90 patients (87%) had solitary
      parathyroid adenoma; 12 patients had multiglandular disease. In one patient no
      enlarged parathyroid gland was found. Overall 77 of 118 abnormal glands (65%)
      were correctly identified by sestamibi scintigraphy. The sensitivity for
      localizing a single parathyroid adenoma was 80%. Patients with incorrect
      scintigrams had a higher proportion of upper pole adenomas than patients with
      correct scans. High glandular weight and high level of serum PTH were important
      factors for detectability. Sestamibi scintigraphy did not predict multiglandular
      disease. However, the use of ioPTH identified 8 of the 9 patients with a positive
      scan (a solitary focus) and multiglandular disease. In contrast, false-negative
      ioPTH led to four unnecessary bilateral explorations in the 63 patients with a
      scan-identified adenoma. With the help of ioPTH, a focused parathyroidectomy was
      accomplished in 43% of scan-negative patients with a solitary adenoma. In
      conclusion, sestamibi scintigraphy is an acceptable method for localizing a
      solitary parathyroid adenoma. However, the technique alone does not reliably
      predict multiglandular disease. Potentially the failure rate in scan-directed
      parathyroidectomy could increase, with up to 10% of patients without ioPTH.

PMID- 15490069
TI  - Focused cervical exploration for primary hyperparathyroidism without
      intraoperative parathyroid hormone monitoring or use of the gamma probe.
AB  - Selected patients with primary hyperparathyroidism (pHPT) who have a positive
      preoperative sestamibi scan can be managed safely and successfully with a focused
      cervical exploration without either adjuvant intraoperative parathyroid hormone
      (PTH) monitoring or use of a gamma probe. This article reports a retrospective
      analysis of a consecutive series of patients surgically treated at a tertiary
      referral center. From August 1998 to August 2002, 100 patients (68 women, 32 men;
      mean age 63 years [range: 29-89 years]) underwent a focused cervical approach
      without intraoperative PTH monitoring or use of the gamma probe after
      perioperative sestamibi injection. The study group comprised 9% of all patients
      (n = 1063) undergoing cervical exploration for pHPT during the study period.
      Ninety patients underwent an initial exploration, and 10 others underwent repeat
      cervical exploration following prior parathyroid (n = 7) or thyroid (n = 3)
      operation. Sestamibi scanning correlated with one enlarged parathyroid gland in
      all patients. Other enlarged glands were, however, not demonstrated in three
      patients (true positive = 97%; false negative = 3%). The single enlarged glands
      excised in all patients had a mean weight of 795 mg (range: 90-3640) and were
      histologically compatible with an adenoma. Postoperatively, 97% of patients were
      eucalcemic. Three patients remained hypercalcemic (3%). Of the three patients
      with persistent hypercalcemia, one underwent successful re-exploration with
      excision of a 500 mg second adenoma, whereas the other two patients (with
      confirmed familial HPT) remained hypercalcemic. Mean hospitalization was 0.5 days
      (range: 0-3 days). There was no operative mortality. No patients had permanent
      hypocalcemia. Postoperative morbidity occurred in three patients: two self
      limiting cervical hematomas and one permanent vocal cord paralysis. Selected
      patients with pHPT due to single-gland disease and an unequivocally positive
      preoperative sestamibi scan can safely and successfully be managed with a focused
      unilateral cervical exploration without either intraoperative PTH monitoring or
      use of the gamma probe. Further experience with this surgical approach seems
      warranted to determine the overall cure rate, operative morbidity, and the
      sensitivity and specificity of preoperative localization studies.

PMID- 15490070
TI  - Optimizing the treatment of AMES high-risk papillary thyroid carcinoma.
AB  - A minority of patients with papillary thyroid carcinoma (PTC) is at high-risk of
      developing recurrent disease and death. Risk group stratification as defined by
      age, metastases to distant site, extrathyroidal invasion, and tumor size (AMES)
      criteria is frequently employed to identify high-risk patients for aggressive
      surgical and adjuvant treatments. The present study aimed at evaluating risk
      factors and the impact of treatment on cause-specific mortality (CSM) in this
      group of high-risk patients. From 1961 to 2000,150 of 499 patients surgically
      treated for PTC were considered as high-risk by AMES criteria. At 10-years CSM
      was significantly higher in high-risk patients (28%) than in low-risk patients
      (2%) (p < 0.0001). The clinicopathologic features, treatment, and outcome of AMES
      high-risk patients were retrospectively studied and risk factors for CSM were
      analyzed. There were 58 men and 92 women with a median age of 62 years (range: 18
      87 years). Bilateral thyroidectomy was performed for 143 (95%) patients and
      concomitant neck dissection was performed for 82 patients (55%). Thirty-six
      patients (24%) underwent incomplete tumor excision with residual disease.
      Radioactive iodine (I131) ablation and external-beam irradiation were
      administered to 102 (68%) and 46 patients (31%), respectively. Over a median
      follow-up of 7.6 years, the overall mortality was 23% and 44%, whereas the CSM
      was 14% and 28% at 5 and 10 years, respectively. Using the Cox proportional
      hazard model, distant metastasis at presentation, incomplete tumor excision, and
      no postoperative I131 treatment were independent prognostic factors of poor
      survival. Patients who underwent an incomplete excision showed improved survival
      after I131 ablation (p = 0.0008), external-beam irradiation (p = 0.02), or both
      forms of treatment (p = 0.04). Within this high-risk AMES group, International
      Union Against Cancer (UICC) pTNM staging and MACIS (Metastasis, Age,
      Completeness, Invasion, Size) scoring correlated significantly with CSM. AMES
      high-risk PTC patients should undergo total thyroidectomy aiming at complete
      tumor resection followed by I131 ablation. External-beam irradiation should be
      added for patients with residual disease after an incomplete excision.

PMID- 15490071
TI  - Recurrent laryngeal nerve palsy in well-differentiated thyroid carcinoma:
      clinicopathologic features and outcome study.
AB  - Involvement of the recurrent laryngeal nerve (RLN) by well-differentiated thyroid
      carcinoma may not invariably lead to unilateral cord palsy, although the presence
      of RLN palsy is associated with locally advanced disease. The present study
      evaluates the clinicopathologic features and outcomes of patients surgically
      treated for well-differentiated thyroid carcinoma with documented nonfunctioning
      RLN at presentation. From 1970 to 2002, 20 of 709 patients undergoing surgical
      treatment for well-differentiated thyroid carcinoma were found to have
      ipsilateral unilateral cord palsy by routine preoperative laryngoscopy. There
      were 5 men and 15 women with a median age of 70 years. Nine patients (45%) did
      not have a clinically palpable thyroid mass, and hoarseness was the primary
      presenting symptom. All patients had histologically confirmed pT4 papillary
      thyroid carcinoma with a median size of 4 cm. Cervical nodal and pulmonary
      metastases were detected in 14 (70%) and 2 (10%) patients, respectively. The
      ipsilateral recurrent nerve was transected in all patients because of gross tumor
      involvement, and 19 patients underwent total or completion total thyroidectomy.
      Resection was incomplete in 15 patients, including 2 who underwent a debulking
      procedure and required reoperation for local control. Postoperative radioactive
      iodine ablation and external-beam irradiation were administered to 18 and 13
      patients, respectively. Over a median follow-up of 4.5 years, 10 patients
      survived without evidence of recurrence, 5 died of disease recurrence, and 5 died
      of unrelated causes. The 5-year and 10-year cause-specific mortality was 17% and
      42%, respectively. Patients developing distant metastasis at presentation or
      during follow-up had a significantly increased cause-specific mortality (p =
      0.002). Preoperative RLN palsy can be the first symptom in patients with locally
      advanced papillary thyroid carcinoma. Despite the adoption of a relatively
      conservative surgical treatment, long-term survival can be achieved in selected
      patients.

PMID- 15490072
TI  - [Long-term effects of 7-year growth hormone substitution on bone metabolism, bone
      density, and bone quality in growth hormone-deficient adults].
AB  - BACKGROUND AND PURPOSE: Subnormal bone mineral density (BMD) and increased
      fracture risk are described in patients with growth hormone deficiency (GHD).
      Growth hormone (GH) has been reported to have beneficial effects on bone in GHD.
      The aim of this study was to investigate the long-term effects of GH replacement
      therapy on bone metabolism, BMD, and bone quality in patients with GHD. PATIENTS
      AND METHODS: 20 adult patients with GHD (eleven male, nine female, mean age 42.5
      years) were included in the study and randomized to either GH or placebo in a
      dose of 0.25 U/kg body weight/week. After 6 months all patients received GH.
      After a 1-year double-blind, placebo-controlled study the patients were followed
      for another 72 months in an open study. The patients were compared to 20 age- und
      sex-matched healthy controls. Bone turnover was determined by ICTP (type I
      collagen carboxyterminal cross-linked telopeptide) as parameter of bone
      resorption and PICP (carboxyterminal propeptide of type I procollagen) as marker
      of bone formation. BMD was measured at the lumbar spine by dual-photon
      absorptiometry (DPA) and at the forearm by single-photon absorptiometry (SPA).
      Apparent phalangeal ultrasound transmission velocity (APU) was assessed as
      parameter of bone quality independent of BMD. RESULTS: At the beginning of the
      study BMD at both measuring sites was lower in patients with GHD than in healthy
      controls. During the 1st year of GH replacement therapy BMD decreased, followed
      by a continuous increase in BMD (about 12%) up to 60 months which remained
      unchanged thereafter, building up a plateau. After 72 months no significant
      difference between the patients and the healthy controls could be detected.
      Concerning parameters of bone turnover, first ICTP as marker of bone resorption
      showed a significant increase, later on the marker of bone formation increased as
      well. APU decreased during the first 6 months of treatment, but had returned to
      its baseline value after 24 months and remained unchanged throughout the rest of
      the study. CONCLUSION: BMD is subnormal in adults with GHD. GH replacement
      therapy stimulates bone turnover in patients with GHD and in the long term such
      stimulation results in an increased BMD. Thereby, GH shows a triphasic action on
      BMD: an initial decrease in BMD during the 1st year, followed by a continuous
      increase in BMD with buildup of a stable plateau after 60 months. The newly
      formed bone seems to have normal bone elasticity.

PMID- 15490073
TI  - [Chronic distress syndrome in patients with Graves' disease].
AB  - PURPOSE: Cross-sectional study to evaluate the psychological distress of patients
      with Graves' disease 5 years after diagnosis. PATIENTS AND METHODS: 45 female
      patients being treated for Graves' disease in a specialized endocrinological
      practice in Wuppertal, Germany, were asked to fill in the Symptom Checklist-90-R
      (SCL-90-R) and the Hospital Anxiety and Depression Scale (HADS). All patients
      were in a euthyroid state for at least 6 months. RESULTS: Patients were found to
      have significantly elevated mean values in the SCL-90-R compared with normal
      values for healthy test candidates. According to the Global Severity Index (GSI)
      more than one third (35.6%) of patients were suffering from psychological
      distress. These patients also showed elevated scores in the anxiety subscale of
      HADS. Almost all patients (95.6%) had elevated scores in the depression subscale
      of HADS. Patients with high levels of psychological distress (GSI > 60) were more
      likely to suffer a relapse than those with normal levels (p < 0.05). Patients in
      latent hyperthyroid state did not show higher levels of psychological distress
      than those with normal thyrotropin (TSH). CONCLUSION: Many patients with a
      history of Graves' disease suffer from chronic psychological distress which
      cannot be explained by the metabolic state of the thyroid gland. Whether this
      finding results from damage to the CNS or reflects a generally increased stress
      vulnerability is unclear. Psychological treatment appears to be indicated in many
      cases of Graves' disease.

PMID- 15490074
TI  - [Concomitant diseases in primary joint hypermobility syndrome].
AB  - The primary joint hypermobility syndrome (pJH) is an overlap disorder of
      connective-tissue dysplasias, which incorporates features seen in the Marfan
      syndromes (MFS), Ehlers-Danlos syndromes (EDS), and osteogenesis imperfecta.
      Patients with pJH usually present arthralgia, back pain, soft-tissue lesions,
      recurrent joint dislocation, or subluxation. Extraarticular features may include,
      e. g., striae cutis, keratoconus, easy bruising, mitral valve prolapse, aortic
      incompetence, aneurysms, pneumothorax, hernia, urinary incontinence, and pelvic
      floor prolapse. Due to the high frequency of critical dissection and rupture, the
      early recognition of rare life-threatening complications such as dilatation of
      the aortic root and aneurysms is important. Therefore, patients (and their family
      members) with pJH should also be examined for life-threatening features seen in
      MFS and EDS.

PMID- 15490075
TI  - [Hepatic encephalopathy].
AB  - Hepatic encephalopathy (HE) may develop within the course of acute or chronic
      liver failure and is characterized by a complex of psychomotor symptoms. In
      addition, HE can be induced by portocaval shunting even in the absence of any
      apparent liver disease. HE is caused by substances, which are either reabsorbed
      from the gut or are a product of the body metabolism. Normally, these substances
      are effectively eliminated during their first passage through the liver. However,
      a decreasing number of functional hepatocytes or the presence of portocaval
      collaterals in liver disease may significantly impair hepatic detoxification.
      Ammonia seems to take a central position in the pathogenesis of HE, although the
      exact cerebral effects of this metabolite are still not known in detail. The
      actual pathogenetic hypotheses are subject of this review. Depending on the
      underlying liver disease, HE is divided into an acute and a chronic form. Chronic
      HE may be present as a persistent or an episodic form, the latter being usually
      induced by defined precipitating factors, such as diet failures, infection and
      gastrointestinal-bleeding. With regard to the psychomotor symptoms and the coma
      depth, the clinical picture is classified into five grades (West Haven criteria).
      Diagnosis is made by clinical examination of the mental status after relevant
      differential diagnoses have been excluded. The only causal therapeutic option in
      the presence of acute or chronic liver failure is liver transplantation.
      Therefore, the indication for transplantation has to be evaluated in all forms of
      HE. Symptomatic treatment has three principal aims: (1) stabilization of
      circulation, oxygen supply, blood sugar and nutrition; (2) identification of the
      precipitating factor and its removal; (3) reduction of ammonia and other
      potential toxins in the circulation. In the case of acute HE, these therapeutic
      aims are complemented by an effective prophylaxis or therapy of brain edema.

PMID- 15490076
TI  - [Intensive care medicine 2004].
AB  - The following survey is supposed to present the most important new therapeutic
      approaches und the current standard of treatment in intensive care medicine
      including pathophysiological and diagnostic aspects of important diseases,
      particularly sepsis, septic and cardiogenic shock. Furthermore, advances in the
      following issues are summarized in detail: ventilation, especially acute
      respiratory distress syndrome (ARDS) and the broad spectrum of non-invasive
      ventilation, new therapeutic options in the field of cardiopulmonary
      resuscitation, and the importance of albumin dialysis in acute liver failure.

PMID- 15490077
TI  - [Drug dosage in renal failure -- traps and aids].

PMID- 15490078
TI  - [70-year-old patient with convulsive syncope].
AB  - BACKGROUND: Syncope is a frequent reason for hospital admissions or emergency
      department visits with a broad differential diagnosis. Convulsive syncope is
      often falsely interpreted as an epileptic disorder. However, due to cerebral
      hypoperfusion, all forms of syncope can be associated with convulsions. In
      elderly patients with coronary heart disease or hypertension, "neurocardiogenic"
      causes, especially the carotid sinus syndrome, should be searched for. In
      general, cardiac pauses > or = 3 s after massage of the carotid sinus are
      required for the diagnosis of inhibitory carotid sinus syndrome. CASE REPORT: In
      the patient presented here, massage of the right carotid sinus provoked sinus
      bradycardia with pauses of 2,2 s and subsequent convulsive syncope. CONCLUSION:
      Additive factors such as coronary heart disease, arteriosclerosis, heart failure,
      and antihypertensive therapy may result in early symptoms of the inhibitory
      carotid sinus syndrome. This underlines the multifactorial pathogenesis of
      syncope, especially in the elderly patient.

PMID- 15490079
TI  - [Arterial hypertension versus hypertensive heart disease].

PMID- 15490081
TI  - [Invasive techniques in emergency medicine. I. Practice-oriented training concept
      to ensure adequately qualified emergency physicians].
AB  - Based on written surveys conducted during the series of workshops entitled
      "Invasive emergency techniques (INTECH)" the aim of this study was to
      characterize defined qualifications of emergency physicians and to discuss by
      examples whether strictly practice-oriented workshops represent a suitable means
      of closing the apparent gaps in training. Our data show clearly that even
      experienced emergency physicians indicated that they lack training in carrying
      out preclinical invasive emergency procedures such as chest tube, cricothyrotomy
      and intraosseous access. Furthermore, they are only very seldom confronted with
      emergency situations in which these procedures could decidedly affect the
      survival of a patient and which, at the same time, put them under extremely high
      emotional pressure. Thus, the didactic concept of continuing education workshops
      that are strictly practice-oriented and that focus in particular on problem areas
      in emergency medicine, can contribute significantly to help close the gaps in
      training and ensure that emergency physicians are highly qualified.

PMID- 15490082
TI  - [Health in today's media society. Institutional health education and television
      entertainment].
AB  - The article sketches concepts of entertaining health education programmes on
      television as discussed in the new sub-discipline of health communication in
      Germany and describes some examples and aspects of cooperation between the
      Federal Center for Health Education (BZgA/FCHE) Cologne as an institutional
      health education agency and German television partners. Specific chances and
      problems of entertaining forms of mass media health education on television are
      discussed. Finally, perspectives for institutional health education in relation
      to television are discussed.

PMID- 15490083
TI  - [Consumer health web service at DIMDI].
AB  - The German Institute of Medical Documentation and Information (DIMDI) extended
      its Internet services targeted at patients in order to meet the rising interest
      of the public for understandable, high-quality medical information. Medical
      terminology is made clear to nonprofessionals by voluminous reference books such
      as the Roche Encyclopedia of Medicine. By using free offers, such as the
      possibilities to search in up-to-date medical literature and studies, laypersons
      can find valuable and quality assured information on their fields of interest.
      Graphic and film material, which is offered in the virtual medical video shop
      (VVFM), covers the en-tire spectrum of specific medical fields and brings the
      areas of prevention, diagnostics, therapy, aftercare as well as nursing care up
      for discussion. It is easy to find physicians, hospitals, and self-help groups.
      Future plans include an extension of the offer to a substantial database
      supported information portal for health-related subjects, which will provide the
      public with simple and speedy access to the health information of the DIM-DI and
      other trustworthy providers under one interface.

PMID- 15490084
TI  - [Patients' competences. What do patients need to know and be able to do?].
AB  - Patients today are rarely patient. More and more they want to be--and should be-
      responsible partners to their doctors and participants in healthcare policy.
      However, even though recent health reforms offered some incentives in this
      direction, the basic requirements are still lacking. One area that is woefully
      neglected is the furthering of the patients' competences. These are described as
      fourfold: competence in dealing with one's own disease and its symptoms;
      relational competence in the interaction between patient and doctor; social
      competence in cooperation with fellow patients, e. g., in self-help groups; and
      democratic competence to participate in formulating healthcare policy. The
      question is asked in which organizations and training measures these competences
      have already been developed. The text concludes with the call for a patient
      academy network operating nationwide.

PMID- 15490085
TI  - [Development and validation of assessment instruments for shared decision
      making].
AB  - The German Ministry for Health and Social Security is funding ten projects to
      introduce shared decision making into clinical practice. The medical problems the
      projects are focussing on were chosen from among various diseases (e. g.
      depression, multiple sclerosis, cancer). The ten projects achieved consensus on a
      core set of instruments for the measurement of process and outcome of the shared
      decision making. Instruments developed in German-speaking countries are currently
      not available. Thus, linguistic and cultural validation had to be performed for
      the core set instruments. The results of the data analysis as well as patient
      interviews demonstrate the need for improving these instruments. Therefore, the
      members of the methodological working group concentrated on the integration of
      these results in a new instrument. In a first step the construct of "shared
      decision making" was defined, followed by a definition of the process elements
      characterising shared decision making. Thereafter, items were developed on the
      basis of the process elements. The new instrument will now be validated for
      different diseases.

PMID- 15490086
TI  - [Development and evaluation of a training program in shared decision making for
      primary care of depressive patients].
AB  - Patient surveys show that many patients want broad information about their
      disease and treatment. Often they are interested to participate in the process of
      medical decision making, which could be realised with the concept of shared
      decision making where patient's values and needs are considered to the same
      extent as the treatment recommendations of evidence-based medicine. In depression
      care, it has been demonstrated so far that the active involvement of patients
      contributes to higher motivation for treatment. For enhancing patient's
      acceptance and motivation to avail themselves of medical treatment, a training
      program for general practitioners was developed and evaluated. It was the aim of
      the training to involve depressive patients in medical decision making. The
      training consists of depression-specific components (e. g. diagnosis, patient
      information, therapy) and general components (communication and shared decision
      making). The training was carried out in five sessions within a 6-month period
      (May to October 2003) embracing 20 h of training. Participants were 20 general
      practitioners in Southwest Germany. Physician's satisfaction with the training
      program is high. Especially in the fields of diagnosis and shared decision making
      the physicians clearly benefited. Transfer of shared decision making into daily
      routine was assessed as possible by the large majority of the trainees.
      Application of the training concept to other diseases and evaluation on the basis
      of daily routine is recommended. The training effects on medical care are
      presently being assessed in a randomised controlled trial.

PMID- 15490087
TI  - [Treatment of acute sinusitis].

PMID- 15490088
TI  - [Clinical application of the endolaryngeal laser measurement technique].
AB  - INTRODUCTION: Laser projection techniques have made morphometric measurement of
      laryngeal structures possible. The clinical application of a new laser
      measurement technique that uses a double reflecting mirror for laser beam
      duplication is discussed. MATERIAL AND METHODS: Endolaryngeal measurement with a
      new two-point laser light projection method was carried out on 25 patients with
      ten different organic lesions of the vocal folds. The laser measurement tool can
      be clipped onto the shaft of a rigid endoscope. A special software program
      enables quick and precise measurements of distances and areas that are in the
      same horizontal plane as the laser spots. FINDINGS: Using this new system, a
      clinical examination of the size of organic lesions of the vocal folds is
      possible, with a precise measurement of endolaryngeal structures being possible
      in all cases. The findings are easily documented, and the examinations can take
      place during routine laryngoscopic investigations. CONCLUSION: Systems for
      endolaryngeal measurements enable morphometric measurements within the larynx.
      Quantitative examinations have become possible in laryngology.

PMID- 15490089
TI  - [Tumour of the maxillary sinus with swelling of the cheek].

PMID- 15490090
TI  - [Organ transplantation in endocrinology. Islet cells and pancreas].
AB  - Pancreas transplantation is a successful and effective procedure resulting in
      tight glucose control. Due to the postoperative morbidity and the need for
      immunosuppression pancreas transplantation should be considered at the time of
      kidney transplantation. Besides this, pancreas transplantation alone should be
      considered for patients with unacceptably poor metabolic control and quality of
      life despite optimal medical treatment. Recently, islet transplantation became a
      less invasive alternative to pancreas transplantation. Due to the lack of long
      term follow-up and due to the need of multiple donor grafts for one recipient,
      islet transplantation should be performed under experimental settings in
      experienced centers. New developments in protecting transplanted islets and in
      the induction of donor-specific tolerance could increase the indication to
      perform the procedure. Therefore alternative sources of beta-cells have to be
      identified.

PMID- 15490091
TI  - DFNA54, a third locus for low-frequency hearing loss.
AB  - Nonsyndromic hereditary hearing impairment (NSHHI) is a highly heterogeneous
      disorder with more than 90 loci mapped, of which nearly one-half of the
      responsible genes are identified. In dominant NSSHI hearing loss is typically
      biased towards the high frequencies while low-frequency hearing loss is unusual.
      Only two NSHHI loci, DFNA1 and DFNA6/14/38, are associated with predominantly low
      frequency loss. We mapped the loci harboring the gene responsible for autosomal
      dominant low-frequency hearing loss in a multigenerational family. The pedigree
      of a Swiss family with low-frequency hearing loss was established. Using genomic
      DNA, DFNA1 and DFNA6/14/38 were excluded by linkage analysis or by direct
      sequencing of the responsible gene. Genome-wide linkage analysis was performed
      using commercially available microsatellite markers. Two-point linkage analysis
      demonstrated linkage to chromosome 5q31, the locus for DFNA15, with a lod score
      of 6.32 at recombination fraction theta=0 for marker D5S436. Critical
      recombinations were seen at markers D5S1972 and D5S410. Sequencing of the
      corresponding gene POU4F3 yielded no pathogenic mutation segregating with the
      affected members. In addition to Wolfram syndrome gene 1 (DFNA6/14/38) and
      diaphanous (DFNA1) there is evidence for a third gene involved in low-frequency
      hearing loss located at DFNA15. Because of the differences in auditory phenotype
      and the absence of pathogenic mutation in the coding region of POU4F3 it is
      likely that there is a second gene in 5q31, designated DFNA54, associated with
      NSHHI.

PMID- 15490092
TI  - The disease that never was.

PMID- 15490093
TI  - Combined use of positive and negative immunomagnetic isolation followed by real
      time RT-PCR for detection of the circulating tumor cells in patients with
      colorectal cancers.
AB  - To establish a novel molecular diagnostic method of detecting circulating tumor
      cells (CTCs) LS174T colon cancer cells were serially diluted with normal blood.
      Additional peripheral blood samples were collected from 25 patients with
      colorectal carcinoma. Mononuclear cells (MNCs) were collected, equally divided
      into four parts, and then cancer cells were enriched by four methods: method A,
      nonimmunobead method; method B, negative immunobead method: CD45 immunomagnetic
      beads were used to deplete the leukocytes; method C, positive immunobead method:
      Ber-EP4 immunomagnetic beads were used to enrich cancer cells; method D, negative
      and-positive immunobead method: CD45 immunomagnetic beads were first used to
      deplete the leukocytes from MNC and then Ber-EP4 immunomagnetic beads were used
      to enrich cancer cells. Finally, real-time quantitative RT-PCR was used to
      monitor mRNA expression of beta2-mircoglobulin (beta2M) and carcinoembryonic
      antigen (CEA). The relative CEA mRNA values were corrected with reference to
      beta2M mRNA, to CEA mRNA/beta2M mRNA ratios according to a CEA mRNA external
      standards prepared with tenfold serial dilutions (1-10(4) IS174T cells) of cDNA
      and beta2M mRNA external standards prepared with tenfold serial dilutions (10(2)
      10(7) leukocytes) of cDNA. In recovery experiments a significant correlation
      between the number of cancer cells and CEA mRNA expression was found when CD45 or
      Ber-EP4 immunomagnetic beads were used alone. A highly significant correlation
      was found when CD45 and Ber-EP4 immunomagnetic beads were used successively. The
      sensitivity of method D was one cancer cell per milliliter of blood. Circulating
      cancer cells were detected in 19 of 25 patients with colorectal cancers. The
      relative CEA mRNA value obtained by method D was the smallest. The positive
      detection rate of circulating cancer cells in patients at Dukes' B, C, and D
      stages were 25.0% (1/4), 83.3% (10/12), and 88.9% (8/9). Combinative use of
      immunomagnetic isolation followed by real-time RT-PCR is a useful technique to
      detect circulating tumor cells in patients with colorectal carcinomas. Applying
      negative and positive immunomagnetic beads successively yields the highest
      correlation with amount of tumor cells.

PMID- 15490094
TI  - Differential-display PCR of peripheral blood for biomarker discovery in chronic
      fatigue syndrome.
AB  - We used differential-display PCR of peripheral blood mononuclear cells (PBMCs) to
      search for candidate biomarkers for chronic fatigue syndrome (CFS). PBMCs were
      collected from a subject with CFS and an age- and sex-matched control before and
      24 h after exercise. RNA expression profiles were generated using 46 primer
      combinations, and the similarity between the individuals was striking.
      Differentially expressed bands were excised, reamplified, and sequenced, yielding
      95 nonredundant sequences, of which 50 matched to known gene transcripts, 38
      matched to genes with unknown functions, and 7 had no similarity to any database
      entry. Most (86%) of the differences between the two subjects were present at
      baseline. Differential expression of ten genes was verified by real-time reverse
      transcription PCR: five (cystatin F, MHC class II, platelet factor 4, fetal brain
      expressed sequence tag, and perforin) were downregulated, and the remaining five
      genes (cathepsin B, DNA polymerase epsilon4, novel EST PBMC191MSt, heparanase
      precursor, and ORF2/L1 element) were upregulated in the subject with CFS. Many of
      these genes have known functions in defense and immunity, thus supporting prior
      suggestions of immune dysregulation in the pathogenesis of CFS. Differential
      display PCR is a powerful tool for identification of candidate biomarkers.
      Investigation of these markers in samples from well-designed epidemiological
      studies of CFS will be required to determine the validity of these candidate
      biomarkers. The real-time reverse-transcription PCR assays that we developed for
      assay of these biomarkers will facilitate high-throughput testing of these
      additional samples.

PMID- 15490095
TI  - European Atlantic: the hottest oil spill hotspot worldwide.
AB  - Oil spills caused by maritime transport of petroleum products are still an
      important source of ocean pollution, especially in main production areas and
      along major transport routes. We here provide a historical and geographic
      analysis of the major oil spills (>700 t) since 1960. Spills were recorded from
      several key marine ecosystems and marine biodiversity hotspots. The past four
      decades have been characterized by an overall decrease in the number of accidents
      and tones of oil spilled in the sea, but this trend was less distinct in the
      European Atlantic area. Recent black tides from the Erika and Prestige vessels
      provided new evidence for the high risk of accidents with serious ecological
      impact in this area, which according to our analysis is historically the most
      important oil spill hotspot worldwide. The English Channel and waters around
      Galicia in Spain were the areas with most accidents. Maritime transport in
      European Atlantic waters has been predicted to continue increasing. Together with
      our own results this suggests that, in addition to measures for increased traffic
      safety, deployment of emergency capacities in the spill hotspot areas may be
      crucial for a sustainable conservation of sea resources and ecosystems.

PMID- 15490096
TI  - Parasitoids and competitors influence colony-level responses in the red imported
      fire ant, Solenopsis invicta.
AB  - Social insect colonies respond to challenges set by a variable environment by re
      allocating work among colony members. In many social insects, such colony-level
      task allocation strategies are achieved through individual decisions that produce
      a self-organized adapting group. We investigated colony responses to parasitoid
      and native ant competitors in the red imported fire ant ( Solenopsis invicta).
      Parasitoid flies affected fire ants by decreasing the proportion of workers
      engaged in foraging. Competitors also altered colony-level behaviours by reducing
      the proportion of foraging ants and by increasing the proportion of roaming
      majors, whose role is colony defence. Interestingly, the presence of both
      parasitism and competition almost always had similar effects on task allocation
      in comparison to each of the biotic factors on its own. Thus, our study uniquely
      demonstrates that the interactive effect of both parasitism and competition is
      not necessarily additive, implying that these biotic factors alter colony
      behaviour in distinct ways. More generally, our work demonstrates the importance
      of studying the dynamics of species interactions in a broader context.

PMID- 15490097
TI  - [Psychosis-induced posttraumatic stress disorder. A rarely diagnosed symptom].
AB  - Patients with severe mental disorders encounter a rather high risk of also
      evolving symptoms of posttraumatic stress disorder (PTSD) as a result of
      psychotic experience. A wide overlap of symptoms makes the differentiation
      between "psychosis-induced PTSD" and "psychotic warning signs" difficult;
      nevertheless, the distinction is important as different therapy strategies must
      be envisaged. A case report of a psychosis-induced PTSD is given.

PMID- 15490098
TI  - Reduced metaphase I associations between the short arms of homologous chromosomes
      in a Hordeum vulgare L. x H. bulbosum L. diploid hybrid influences the frequency
      of recombinant progeny.
AB  - Hordeum vulgare (cultivated barley) x H. bulbosum (bulbous barley grass) hybrids
      have been used to obtain disease-resistant recombinant lines (RLs). The RLs
      contain chromatin transferred from the wild species mostly onto the long arms of
      recipient barley chromosomes. To determine whether differences in meiotic
      metaphase I (MI) associations between the long and short arms of homologous
      chromosomes can account for the preponderance of introgressions on the long arms,
      we carried out fluorescent in situ hybridisation on MI chromosome preparations
      obtained from pollen mother cells of a diploid interspecific hybrid. By using
      various probes, we established that MI associations between the long arms
      occurred more frequently than between the short arms for the five chromosomes
      tested.

PMID- 15490099
TI  - Molecular mapping of Stb1, a potentially durable gene for resistance to septoria
      tritici blotch in wheat.
AB  - Septoria tritici blotch (STB), caused by the ascomycete Mycosphaerella
      graminicola (anamorph Septoria tritici), was the most destructive disease of
      wheat in Indiana and adjacent states before deployment of the resistance gene
      Stb1 during the early 1970s. Since then, Stb1 has provided durable protection
      against STB in widely grown wheat cultivars. However, its chromosomal location
      and allelic relationships to most other STB genes are not known, so the molecular
      mapping of Stb1 is of great interest. Genetic analyses and molecular mapping were
      performed for two mapping populations. A total of 148 F1 plants (mapping
      population I) were derived from a three-way cross between the resistant line
      P881072-75-1 and the susceptible lines P881072-75-2 and Monon, and 106 F6
      recombinant-inbred lines (mapping population II) were developed from a cross
      between the resistant line 72626E2-12-9-1 and the susceptible cultivar Arthur.
      Bulked-segregant analysis with random amplified polymorphic DNA (RAPD), amplified
      fragment length polymorphism (AFLP), and microsatellite or simple-sequence repeat
      (SSR) markers was conducted to identify those that were putatively linked to the
      Stb1 gene. Segregation analyses confirmed that a single dominant gene controls
      the resistance to M. graminicola in each mapping population. Two RAPD markers,
      G7(1200) and H19(520), were tightly linked to Stb1 in wheat line P881072-75-1 at
      distances of less than 0.68 cM and 1.4 cM, respectively. In mapping population
      II, the most closely linked marker was SSR Xbarc74, which was 2.8 cM proximal to
      Stb1 on chromosome 5BL. Microsatellite loci Xgwm335 and Xgwm213 also were
      proximal to Stb1 at distances of 7.4 cM and 8.3 cM, respectively. The flanking
      AFLP marker, EcoRI-AGC/ MseI-CTA-1, was 8.4 cM distal to Stb1. The two RAPD
      markers, G7(1200) and H19(520), and AFLP EcoRI-AGC/ MseI-CTA-1, were cloned and
      sequenced for conversion into sequence-characterized amplified region (SCAR)
      markers. Only RAPD allele H19(520) could be converted successfully, and none of
      the SCAR markers was diagnostic for the Stb1 locus. Analysis of SSR and the
      original RAPD primers on several 5BL deletion stocks positioned the Stb1 locus in
      the region delineated by chromosome breakpoints at fraction lengths 0.59 and
      0.75. The molecular markers tightly linked to Stb1 could be useful for marker
      assisted selection and for pyramiding of Stb1 with other genes for resistance to
      M. graminicola in wheat.

PMID- 15490100
TI  - High-density AFLP map of nonbrittle rachis 1 (btr1) and 2 (btr2) genes in barley
      (Hordeum vulgare L.).
AB  - Wild relatives of barley disperse their seeds at maturity by means of their
      brittle rachis. In cultivated barley, brittleness of the rachis was lost during
      domestication. Nonbrittle rachis of occidental barley lines is controlled by a
      single gene (btr1) on chromosome 3H. However, nonbrittle rachis of oriental
      barley lines is controlled by a major gene (btr2) on chromosome 3H and two
      quantitative trait loci on chromosomes 5HL and 7H. This result suggests multiple
      mutations of the genes involved in the formation of brittle rachis in oriental
      lines. The btr1 and btr2 loci did not recombine in the mapping population
      analyzed. This result agrees with the theory of tight linkage between the two
      loci. A high-density amplified fragment-length polymorphism (AFLP) map of the
      btr1/btr2 region was constructed, providing an average density of 0.08 cM/locus.
      A phylogenetic tree based on the AFLPs showed clear separation of occidental and
      oriental barley lines. Thus, barley consists of at least two lineages as far as
      revealed by molecular markers linked to nonbrittle rachis genes.

PMID- 15490101
TI  - A high-density microsatellite consensus map for bread wheat (Triticum aestivum
      L.).
AB  - A microsatellite consensus map was constructed by joining four independent
      genetic maps of bread wheat. Three of the maps were F(1)-derived, doubled-haploid
      line populations and the fourth population was 'Synthetic' x 'Opata', an F(6)
      derived, recombinant-inbred line population. Microsatellite markers from
      different research groups including the Wheat Microsatellite Consortium, GWM,
      GDM, CFA, CFD, and BARC were used in the mapping. A sufficient number of common
      loci between genetic maps, ranging from 52 to 232 loci, were mapped on different
      populations to facilitate joining the maps. Four genetic maps were developed
      using MapMaker V3.0 and JoinMap V3.0. The software CMap, a comparative map
      viewer, was used to align the four maps and identify potential errors based on
      consensus. JoinMap V3.0 was used to calculate marker order and recombination
      distances based on the consensus of the four maps. A total of 1,235
      microsatellite loci were mapped, covering 2,569 cM, giving an average interval
      distance of 2.2 cM. This consensus map represents the highest-density public
      microsatellite map of wheat and is accompanied by an allele database showing the
      parent allele sizes for every marker mapped. This enables users to predict allele
      sizes in new breeding populations and develop molecular breeding and genomics
      strategies.

PMID- 15490102
TI  - Yield response to water deficit in an upland rice mapping population:
      associations among traits and genetic markers.
AB  - A population of recombinant inbred rice lines from a cross between the upland
      japonica cultivar Azucena and the upland indica cultivar Bala was evaluated in a
      series of upland field experiments. Water stress was imposed during the
      reproductive stage by managed irrigation during the dry season, while control
      treatments were maintained in aerobic, well-irrigated conditions. Water deficit
      resulted in a yield reduction of 17 to 50%. The genetic correlation between
      stress and control yields was quite high when stress was mild, and the
      heritability of yield was similar in stress and control treatments across both
      years of this study. Genetic correlations between secondary traits such as leaf
      rolling and drying and yield under stress varied from high (leaf drying) to
      insignificant (leaf rolling). Lines with superior yield tended to have fewer
      panicles and larger grain size than the high-yielding parent, Bala, even though
      the panicle number was positively correlated with yield and the thousand-grain
      weight was not associated with yield for the population as a whole. Analysis of
      quantitative trait loci (QTLs) for yield and yield components allowed the
      identification of 31 regions associated with growth or yield components. Superior
      alleles came from either parent. Several of the regions identified had also been
      reported for root mass at depth or maximum root length in this population in
      other studies made under controlled environments, and for leaf drying (LD) in
      field studies. However, the direction of the effect of QTLs was not consistent,
      which indicates that there was not necessarily a causal relationship between
      these secondary traits and performance. We conclude that mapping populations can
      provide novel insights on the actual relationships between yield components and
      secondary traits in stress and control environments and can allow identification
      of significant QTLs for yield components under drought stress.

PMID- 15490103
TI  - Rpp1, a dominant gene providing race-specific resistance to rose powdery mildew (
      Podosphaera pannosa): molecular mapping, SCAR development and confirmation of
      disease resistance data.
AB  - We have previously demonstrated that in the diploid rose population 97/9
      resistance to the powdery mildew race 9 is controlled by a major dominant
      resistance gene, Rpp1. In the study reported here, we isolated several molecular
      markers closely linked to Rpp1 via bulked segregant analysis, with the gene being
      tagged in an interval of 5 cM between the two most adjacent markers. It was
      possible to convert the most closely linked amplified fragment length polymorphic
      (AFLP) marker into a sequence-characterised amplified region (SCAR) segregating
      in the same manner. Indirect mapping of Rpp1 in relation to the black spot
      resistance gene Rdr1 revealed no linkage between the two R genes. Furthermore,
      the genetic model based on a single dominant resistance gene was supported by the
      marker data.

PMID- 15490104
TI  - Construction of bacterial artificial chromosome libraries and their application
      in developing PCR-based markers closely linked to a major locus conditioning
      bruchid resistance in mungbean (Vigna radiata L. Wilczek).
AB  - Bacterial artificial chromosome (BAC) libraries have been widely used in
      different aspects of genome research. In this paper we report the construction of
      the first mungbean (Vigna radiata L. Wilczek) BAC libraries. These BAC clones
      were obtained from two ligations and represent an estimated 3.5 genome
      equivalents. This correlated well with the screening of nine random single-copy
      restriction fragment length polymorphism probes, which detected on average three
      BACs each. These mungbean clones were successfully used in the development of two
      PCR-based markers linked closely with a major locus conditioning bruchid
      (Callosobruchus chinesis) resistance. These markers will be invaluable in
      facilitating the introgression of bruchid resistance into breeding programmes as
      well as the further characterisation of the resistance locus.

PMID- 15490105
TI  - The establishment of 'essential derivation' among rose varieties, using AFLP.
AB  - In the International Union for the Protection of New Varieties of Plants Act of
      1991, mutation is mentioned as one of the mechanisms to obtain an 'essentially
      derived' variety (EDV). For the implementation of the EDV concept in the case of
      mutation, it is important that the level of genetic relatedness between an
      initial variety and derived mutant varieties can clearly be distinguished from
      the level of relatedness between arbitrary pairs of varieties without a
      derivation relation. Conditions to be fulfilled for such a distinction include
      enough genetic differentiation in the germplasm pool of interest, sufficiently
      low levels of genomic sampling error and technical laboratory error and high
      reproducibility within and between laboratories. In rose, mutants or 'sports' are
      frequently observed during multiplication, making it a suitable crop for studying
      the possibilities for introduction of the EDV concept in ornamentals. We studied
      genetic similarities among 83 rose varieties, including 13 mutant groups. Twelve
      AFLP primer combinations generated 284 polymorphic markers and 114 monomorphic
      (fixed) bands. Pair-wise Jaccard similarities between original varieties and
      derived mutants were close to 1.0 (>0.96), whereas all similarities between
      original varieties were below 0.80, with 75% of the non-mutant similarities even
      being below 0.50. Values less than 1.0 for similarity among original varieties
      and their mutants were to a major extent due to scoring errors. Error rates in
      automated scoring proved to be lower than those in manually scored and
      transferred data. Experimental errors, even between laboratories, turned out to
      be very small. On the basis of a consistent and large difference between
      similarities, relations between an original variety and its mutants can easily be
      identified and distinguished from relations between original varieties. These
      results open the way for implementing the essential derivation concept in rose.

PMID- 15490106
TI  - Molecular characterization and isolation of the F/f gene for femaleness in
      cucumber ( Cucumis sativus L.).
AB  - The biological processes leading to sex expression in plants are of tremendous
      practical significance for fruit production of many agricultural and
      horticultural crops. Sex-expression studies in cucumber showed that the different
      sex types are determined by three major genes: M/m, F/f and A/a. The M/m gene in
      the dominant condition suppresses stamina development and thus leads to female
      flowers. The F/f gene in the dominant condition shifts the monoecious sex pattern
      downwards and promotes femaleness by causing a higher level of ethylene in the
      plant. To investigate the molecular character of the gene F/f, we used nearly
      isogenic gynoecious ( MMFF) and monoecious ( MMff) lines (NIL) produced by our
      own backcross programme. Our investigations confirmed the result of other groups
      that an additional genomic ACC synthase (key enzyme of ethylene biosynthesis)
      sequence ( CsACS1G) should exist in gynoecious genotypes. A linkage was also
      verified between the F/f locus and the CsACS1G sequence with our plant material.
      After the exploration of different Southern hybridization patterns originating
      from different CsACS1 probes, a restriction map of the CsACS1 locus was
      constructed. By using this restriction map, the duplication of the CsACS1 gene
      and following mutation of the CsACS1G gene could be explained. The promoter
      regions of the genes CsACS1G and CsACS1 were amplified in a splinkerette PCR and
      sequenced. An exclusive amplification of the new isolated sequence ( CsACS1G) in
      gynoecious ( MMFF) and sub-gynoecious ( MMFf) genotypes confirmed that the
      isolated gene is the dominant F allele.

PMID- 15490107
TI  - Detection of quantitative trait loci controlling bud burst and height growth in
      Quercus robur L.
AB  - Genetic variation of bud burst and early growth components was estimated in a
      full-sib family of Quercus robur L. comprising 278 offspring. The full sibs were
      vegetatively propagated, and phenotypic assessments were made in three field
      tests. This two-generation pedigree was also used to construct a genetic linkage
      map (12 linkage groups, 128 markers) and locate quantitative trait loci (QTLs)
      controlling bud burst and growth components. In each field test, the date of bud
      burst extended over a period of 20 days from the earliest to the latest clone.
      Bud burst exhibited higher heritability (0.15-0.51) than growth components (0.04
      0.23) and also higher correlations across field tests. Over the three tests there
      were 32 independent detected QTLs ( P<or=5% at the chromosome level) controlling
      bud burst, which likely represent at least 12 unique genes or chromosomal regions
      controlling this trait. QTLs explained from 3% to 11% of the variance of the
      clonal means. The number of QTLs controlling height growth components was lower
      and varied between two and four. However the contribution of each QTL to the
      variance of the clonal mean was higher (from 4% to 19%). These results indicate
      that the genetic architecture of two important fitness-related traits are quite
      different. On the one hand, bud burst is controlled by several QTLs with rather
      low to moderate effects, but contributing to a high genetic (additive) variance.
      On the other hand, height growth depends on fewer QTLs with moderate to strong
      effects, resulting in lower heritabilities of the trait.

PMID- 15490108
TI  - Hyperglycaemia-induced superoxide production decreases eNOS expression via AP-1
      activation in aortic endothelial cells.
AB  - AIMS/HYPOTHESIS: Hyperglycaemia is a primary cause of vascular complications in
      diabetes. A hallmark of these vascular complications is endothelial cell
      dysfunction, which is partly due to the reduced production of nitric oxide. The
      aim of this study was to investigate the regulation of endothelial nitric oxide
      synthase (eNOS) activity by acute and chronic elevated glucose. METHODS: Human
      aortic endothelial cells were cultured in 5.5 mmol/l (NG) or 25 mmol/l glucose
      (HG) for 4 h, 1 day, 3 days or 7 days. Mouse aortic endothelial cells were
      freshly isolated from C57BL/6J control and diabetic db/db mice. The expression
      and activity of eNOS were measured using quantitative PCR and nitrite
      measurements respectively. The binding of activator protein-1 (AP-1) to DNA in
      nuclear extracts was determined using electrophoretic mobility-shift assays.
      RESULTS: Acute exposure (4 h) of human aortic endothelial cells to 25 mmol/l
      glucose moderately increased eNOS activity and eNOS mRNA and protein expression.
      In contrast, chronic exposure to elevated glucose (25 mmol/l for 7 days) reduced
      total nitrite levels (46% reduction), levels of eNOS mRNA (46% reduction) and
      eNOS protein (65% reduction). In addition, AP-1 DNA binding activity was
      increased in chronic HG-cultured human aortic endothelial cells, and this effect
      was reduced by the specific inhibition of reactive oxygen species production
      through the mitochondrial electron transport chain. Mutation of AP-1 sites in the
      human eNOS promoter reversed the effects of HG. Compared with C57BL/6J control
      mice, eNOS mRNA levels in diabetic db/db mouse aortic endothelial cells were
      reduced by 60%. This decrease was reversed by the overexpression of manganese
      superoxide dismutase using an adenoviral construct. CONCLUSIONS/INTERPRETATION:
      In diabetes, the expression and activity of eNOS is regulated through glucose
      mediated mitochondrial production of reactive oxygen species and activation of
      the oxidative stress transcription factor AP-1.

PMID- 15490110
TI  - Animal models have little to teach us about type 1 diabetes: 1. In support of
      this proposal.

PMID- 15490111
TI  - Renal disease in rats with type 2 diabetes is associated with decreased renal
      nitric oxide production.
AB  - AIMS/HYPOTHESIS: In several other models of chronic renal disease, decreases in
      renal nitric oxide activity and nitric oxide synthase (NOS) protein abundance
      have been demonstrated. Here, we studied diabetic obese Zucker (ZDF Gmi fa/fa)
      rats that develop severe hyperglycaemia and renal disease, together with their
      lean control animals, to determine if renal nitric oxide deficiency also occurs
      in this model. METHODS: Obese Zucker rats aged 10 to 12 weeks were maintained on
      Purina 5008 diet until 4, 8, or 11 months of age and compared with similarly
      maintained, 4- and 11-month-old lean Zucker rats. NOS activity and abundance of
      endothelial NOS (eNOS) and neuronal NOS (nNOS) were measured on homogenates of
      kidney cortex. Blood was analysed for glucose, lipids, creatinine, and blood urea
      nitrogen and kidney tissue was obtained for histology. RESULTS: Obese rats
      exhibited severe hyperglycaemia from 4 months of age and developed increasing
      hyperlipidaemia, proteinuria, and decreasing renal function with age compared to
      lean counterparts. At 4 months cortical NOS activity and nNOS abundance were
      lower in obese rats than in lean ones. At 11 months NOS activity remained
      depressed and nNOS abundance had declined further in obese rats.
      Glomerulosclerosis in the obese rats was mild at 4 months, becoming severe by 11
      months. Lean rats had only mild age-dependent increases in glomerular injury.
      CONCLUSIONS/INTERPRETATION: The chronic renal disease that occurs in
      hyperglycaemic, obese Zucker rats is associated with decreased renal cortical
      nitric oxide production and increasing renal injury, although the changes do not
      resemble those of diabetic nephropathy in man.

PMID- 15490112
TI  - [The surgical management of spastic foot deformities].
AB  - Any surgical treatment of spastic foot deformities must be preceded by an exact
      preoperative analysis of every aspect of the deformity and its functional
      consequences. The goals of surgical treatment are correction of the deformity,
      reestablishment of the stability of the foot and preservation of functionally
      important ranges of motion and muscle strength. These goals can usually be
      achieved only by a package of several simultaneous procedures. The foot must
      never be treated in isolation. Proximal joints have to be considered as well as
      the opposite side, because a plantigrade position of the foot is only possible
      when the leg is straight. Any postoperative evaluation must also take into
      account the proximal joints and the opposite leg in unilateral cases. The mere
      static evaluation of the postoperative results by reporting clinical and
      radiographic values should be supplemented by dynamic measurements which allow
      more insight into the functional results.

PMID- 15490113
TI  - [Orthotics and cerebral palsy. Established treatments and trends in orthopaedic
      devices for patients with cerebral palsy].
AB  - The surgical and pharmacological treatment of cerebral palsy patients is, in many
      cases, complemented by orthopaedic appliances. New knowledge and materials have
      expanded the possibilities for orthotic treatment in the last years, but have
      also led to confusion on the correct technology to use in different cases. This
      paper presents an overview of the current orthotic methods in cerebral palsy
      patients. Initially, we present the different ideas and show the limitations of
      the treatment. Next, we consider the problem of spastic hip dislocation and the
      possibilities of positioning the patients. Beds and splints cut from foam allow
      safe positioning of severely disabled patients without the risk of pressure
      sores. This appliance may prevent spastic hip dislocation in the long-term.
      Results of a patient questionnaire are presented. The third section deals with
      experiences with full contact braces and differences in their construction
      compared to conventional corsets. Our own results from a patient questionnaire
      and clinical cases will be presented. The use of a full contact brace may have a
      positive influence on the development of the spastic scoliosis.

PMID- 15490114
TI  - [New bone formation by extracorporeal shock waves. Dependence of induction on
      energy flux density].
AB  - BACKGROUND: The purpose of this study was to test the hypothesis that shock waves
      can induce new bone formation even without cortical fractures and periosteal
      detachment as suggested in the literature. METHODS: Extracorporeal shock waves
      with energy flux densities between 0 mJ/mm(2) (sham treatment) and 1.2 mJ/mm(2)
      were applied in vivo to the distal femoral region of rabbits (1500 pulses at 1 Hz
      frequency each). Oxytetracycline was injected on days 5-9 and the animals were
      sacrificed on day 10. Sections of both femora of all animals were investigated
      with broadband fluorescence microscopy and contact microradiography for new
      periosteal and endosteal bone, periosteal detachment, cortical fractures, and
      trabecular bone with callus. RESULTS: Shock waves with energy flux densities of
      0.9 mJ/mm(2) and 1.2 mJ/mm(2) resulted in new periosteal bone formation in the
      presence of cortical fractures and periosteal detachment. After application of
      shock waves with energy flux density of 0.5 mJ/mm(2), clearly detectable signs of
      new periosteal bone formation were observed without cortical fractures or
      periosteal detachment. CONCLUSIONS: The results of this study challenge the
      current view in the literature that the creation of cortical fractures and
      periosteal detachment are prerequisites for new bone formation mediated by
      extracorporeal shock waves.

PMID- 15490116
TI  - [ESKA (CUT) endoprosthesis].
AB  - The ESKA femoral neck endoprosthesis (CUT) is a mini endoprosthesis anchored in
      the metaphysis for surgical management of young arthrosis patients with good bone
      quality. The necessary surgical intervention can be considered minimally invasive
      and adequate because only the affected femoral head is removed. The preserved
      femoral neck is used for fixation of the endoprosthesis to obtain proximal
      physiological force transmission and avoid stress shielding. Since the diaphyseal
      marrow cavity is not opened, the procedures entail decidedly less blood loss.
      Should the need arise to change the endoprosthesis, an endoprosthetic stem
      anchored in the diaphysis can easily be implanted after resection of the femoral
      neck near the base.

PMID- 15490115
TI  - [HAC-titanium as an implant for interbody fusion in spinal canal stenosis of the
      cervical spine. Six-year clinical trial].
AB  - A total of 102 patients were operated on in 134 levels because of an isolated
      spondylotic cervical stenosis in 6 years. A titanium implant coated with
      hydroxyapatite ceramic (HAC) was inserted. The average age of the patients was 53
      years. The final clinical and radiological follow-up was performed after 15
      months. The functional outcome was classified as good to excellent (Odoms's
      score) in 83.8% of the patients. Implant-related complications requiring revision
      surgery included two dislocated dowels and one vertebral collapse in a
      bisegmental operation. After 6 weeks beginning of bony growth around the implant
      was seen in 38% of all inserted titanium cages on roentgenograms. A complete
      solid bony incorporation was shown in 91.2% of the fused segments after 6 months
      and in 96% after 12 months or at follow-up, respectively. These results
      illustrate the efficacy of the easy to handle HAC titanium implant, demonstrating
      that this technique achieves good clinical outcome with the same complication
      rate as comparable techniques.

PMID- 15490117
TI  - D-dimer for the diagnosis of pulmonary embolism: a call for sticking to evidence.

PMID- 15490119
TI  - True occult bladder perforation during placement of tension-free vaginal tape.
AB  - Bladder perforation is one of the most common complications of the trans-vaginal
      tape (TVT) procedure, and is generally identified on routine intra-operative
      cystoscopy. We present a case of occult bladder perforation occurring during the
      TVT procedure that could not be identified by cystoscopy. A 57-year-old woman
      underwent TVT placement for treatment of stress urinary incontinence. A bladder
      perforation, suspected because of clear fluid at one of the abdominal incision
      sites, could not be identified with cystoscopy, but was confirmed with bladder
      installation of sterile infant formula. The tape was removed and the bladder was
      drained for 48 h. The patient's recovery was uneventful and she subsequently
      underwent TVT placement without complication. Cystoscopy alone may be inadequate
      for identification of some bladder perforations during the TVT procedure.
      Awareness of alternative methods of identification is essential.

PMID- 15490120
TI  - An estimate of the worldwide prevalence, mortality and disability associated with
      hip fracture.
AB  - The aim of this study was to quantify the global burden of osteoporosis as judged
      by hip fracture and the burden in different socio-economic regions of the world.
      The population mortality in 1990 and the incidence of hip fracture in different
      regions were identified, where possible in 1990. Excess mortality from hip
      fracture used data for Sweden, and disability weights were assigned to survivors
      from hip fracture. In 1990 there were an estimated 1.31 million new hip
      fractures, and the prevalence of hip fractures with disability was 4.48 million.
      There were 740,000 deaths estimated to be associated with hip fracture. There
      were 1.75 million disability adjusted life-years lost, representing 0.1% of the
      global burden of disease world-wide and 1.4% of the burden amongst women from the
      established market economies. We conclude that hip fracture is a significant
      cause of morbidity and mortality worldwide.

PMID- 15490121
TI  - Musculoskeletal and functional muscle-bone analysis in children with rheumatic
      disease using peripheral quantitative computed tomography.
AB  - Bone demineralization is a severe complication of juvenile idiopathic arthritis
      (JIA) and other rheumatic diseases. To identify patients, who are at risk of bone
      disease, musculoskeletal analysis is performed. Furthermore, a more functional
      approach is needed to assess, whether bone strength is adequate for muscle force
      and whether muscle force is adequate for body size. In patients with a chronic
      disease it is most important to differentiate between primary bone problems and
      those that are secondary to low muscle force. To implement this approach, we
      measured musculoskeletal parameters of the radius in 94 patients with juvenile
      idiopathic arthritis of different subtypes and connective tissue disease using
      peripheral quantitative computed tomography. The four groups consisted of
      patients with oligoarticular (n = 31), polyarticular (n = 27), systemic JIA (n =
      20) and connective tissue disease (CTD) (n = 16). All patients with systemic JIA
      and CTD and 56% of the patients with polyarticular JIA were under treatment with
      glucocorticoids. In general, the longer the duration of the disease and the more
      severe the subtype of the rheumatic disease, the shorter the height and the lower
      the bone density and bone strength parameters. Mean height, bone mineral content
      (BMC) and muscle cross-sectional area (CSA) were low for age, but muscle CSA was
      normal for height with the exception of patients with polyarticular disease. In
      the systemic JIA group the ratio of BMC per muscle CSA was decreased by -1.7+/
      2.7 SD (P < 0.05), suggesting that bone strength was not adequately adapted to
      muscle force. This was even more expressed in females than in males (14 versus
      3). These patients need closer follow up and potential specific therapeutic
      intervention.

PMID- 15490122
TI  - Studies on hydrogenase activity and chlorobenzene respiration in Dehalococcoides
      sp. strain CBDB1.
AB  - Hydrogen oxidation and electron transport were studied in the chlorobenzene
      utilizing anaerobe Dehalococcoides sp. strain CBDB1. While Cu(2+) and Hg(2+) ions
      irreversibly inhibited hydrogenase activity in intact cells, Ni(2+) ions
      inhibited reversibly. About 80% of the initial hydrogenase activity was
      inactivated within 30 s when the cells were exposed to air. In contrast,
      hydrogenase was active at a redox potential of +10 mV when this redox potential
      was established anoxically with a redox indicator. Viologen dyes served both as
      electron acceptor for hydrogenase and electron donor for the dehalogenase. A
      menaquinone analogue, 2,3-dimethyl 1,4-naphthoquinone, served neither as electron
      acceptor for the hydrogenase nor as electron donor for the dehalogenase. In
      addition, the menaquinone antagonist 2-n-heptyl-4-hydroxyquinoline-N-oxide had no
      effect on dechlorination catalyzed by cell suspensions or isolated membranes with
      hydrogen as electron donor, lending further support to the notion that
      menaquinone is not involved in electron transport. The ionophores
      tetrachlorosalicylanilide and carbonylcyanide m-chlorophenylhydrazone did not
      inhibit dechlorination by cell suspensions, indicating that strain CBDB1 does not
      require reverse electron transport. The ATP-synthase inhibitor N,N'
      dicyclohexylcarbodiimide inhibited the dechlorination reaction with cell
      suspensions; however, the latter effect was partially relieved by the addition of
      tetrachlorosalicylanilide. 1,2,3,4-tetrachlorobenzene strongly inhibited
      dechlorination of other chlorobenzenes by cell suspensions with hydrogen as
      electron donor, but it did not interfere with either hydrogenase or dehalogenase
      activity.

PMID- 15490124
TI  - Oxaloacetate decarboxylase of Archaeoglobus fulgidus: cloning of genes and
      expression in Escherichia coli.
AB  - Archaeoglobus fulgidus harbors three consecutive and one distantly located gene
      with similarity to the oxaloacetate decarboxylase Na+ pump of Klebsiella
      pneumoniae (KpOadGAB). The water-soluble carboxyl transferase (AfOadA) and the
      biotin protein (AfOadC) were readily synthesized in Escherichia coli, but the
      membrane-bound subunits AfOadB and AfOadG were not. AfOadA was affinity purified
      from inclusion bodies after refolding and AfOadC was affinity purified from the
      cytosol. Isolated AfOadA catalyzed the carboxyl transfer from [4-14C]
      oxaloacetate to the prosthetic biotin group of AfOadC or the corresponding biotin
      domain of KpOadA. Conversely, the carboxyl transferase domain of KpOadA exhibited
      catalytic activity not only with its pertinent biotin domain but also withAfOadC.

PMID- 15490125
TI  - Production of nitric oxide elevates nitrosothiol formation resulting in decreased
      glutathione in macrophages exposed to asbestos or asbestos substitutes.
AB  - The purpose of this study was to investigate the effects of pneumoconiogenic
      particles, such as asbestos, on nitrosothiol formation in macrophages. In
      addition, the effects of man-made mineral fibers (MMMFs) were also evaluated,
      because they have come into heavy use as substitutes for asbestos. RAW264.7 cells
      and J774 cells of murine macrophage cell lines were cultured with chrysotile B
      (CH) asbestos, crocidolite (CR) asbestos, or MMMFs comprised of glass wool (GW),
      rock wool (RW), or ceramic (RF1). All of these fibers significantly increased
      nitric oxide (NO) production in the culture with macrophages. Chrysotile B, CR,
      and GW significantly decreased the level of reduced glutathione (GSH) in RAW264.7
      cells. S-nitrosothiol (RS-NO) formation was increased by both types of cells on
      exposure to every fiber. A large portion of this increased RS-NO may be in the
      form of S-nitrosoglutathione (GS-NO), because GSH is the most abundant thiol
      substance in the cell. Both CH and GW significantly increased superoxide anion in
      the media cultured of RAW264.7 cells. These results indicate that macrophages
      exposed to asbestos or MMMFs are subject to oxidative stress, not only through
      the generation of reactive oxygen and nitrogen species, but also through
      decreases in the level of the cellular antioxidant, GSH, by GS-NO formation. The
      increase of RS-NO in macrophages exposed to asbestos or MMMFs may deserve more
      attention as the indicator of continuous oxidative stress by NO on cells and
      tissues, which causes inflammation and involves the development of asbestos
      induced diseases.

PMID- 15490126
TI  - Effects of dioxane on cytochrome P450 enzymes in liver, kidney, lung and nasal
      mucosa of rat.
AB  - The effect of acute and chronic dioxane administration on hepatic, renal,
      pulmonary and nasal mucosa P450 enzymes and liver toxicity were investigated in
      male rats. The acute treatment consisted of two doses (2 g/kg) of dioxane given
      for 2 days by gavage, whereas the chronic treatment consisted of 1.5% of dioxane
      in drinking water for 10 days. Both the acute and chronic dioxane treatments
      induced cytochrome P450 2B1/2- and P450 2E1-dependent microsomal monooxygenase
      activities (pentoxyresorufin O-depentylase and p-nitrophenol hydroxylase) in the
      liver, whereas in the kidney and nasal mucosa, only the 2E1 marker activities
      were enhanced. In addition in the liver, an induction of 2alpha-testosterone
      hydroxylase (associated with the constitutive and hormone-dependent P450 2C11)
      was also revealed, whereas the hepatic P450 4A-dependent omega-lauric acid
      hydroxylase was not enhanced by any dioxane treatment. These inductions were
      mostly confirmed by western blot analysis of liver, kidney and nasal mucosa
      microsomes. In the lung, no alteration of P450 activities was observed. To assess
      the mechanism of 2E1 induction, the hepatic, renal and nasal mucosa 2E1 mRNA
      levels were also examined. Following two kinds of dioxane administration, in the
      liver the 2E1 induction was not accompanied by a significant alteration of 2E1
      mRNA levels, while both in the kidney and nasal mucosa the 2E1 mRNA increased
      about 2- to 3-fold, indicating an organ-specific regulation of this P450 isoform.
      Furthermore, dioxane was unable to alter the plasma alanine aminotransferase
      activity and hepatic glutathione (GSH) content, examined as an index of toxicity,
      when it was administered into rats with P450 2B1/2 and 2E1 preinduced by
      phenobarbital or fasting pretreatment. These results support the lack of or a
      poor formation of reactive and toxic intermediates during the biotrasformation of
      this solvent, even when its metabolism was enhanced by P450 inducers. The chronic
      administration of dioxane was also unable to induce the palmitoyl CoA oxidase, a
      marker of peroxisome proliferation, excluding this as a way to explain its
      toxicity. Thus, although the mechanism of dioxane carcinogenicity remains
      unclear, the present results suggest that the induction of 2E1 following a
      prolonged administration of dioxane might provide oxygen radical species, and
      thereby contribute to its organ-specific toxicity.

PMID- 15490130
TI  - Simultaneous determination of multiple constituents in real beer samples of
      different origins by capillary zone electrophoresis.
AB  - Simultaneous determination of alcohols, amines, amino acids, flavonoids, and
      purine and pyrimidine bases in bottled beer samples directly without any pre
      treatment was carried out by capillary zone electrophoresis with diode-array
      detection. Electrolyte conditions such as pH, composition and concentration of
      the buffer, working voltage and type and time of injection were checked. The best
      separation of the cited analytes was achieved in 70 mM sodium borate solution and
      pH 10.25. The detection limits were from 2.1 to 5.6 mg L(-1) for the 18 compounds
      studied. The developed method is rapid, sensitive and quantitative and has been
      applied to seven types of international bottled beers of different origins bought
      locally.

PMID- 15490131
TI  - Morphological basis for coordination of growth and reproduction processes in the
      CNS of two terrestrial snails.
AB  - The morphology of cells immunoreactive to an antibody against molluscan insulin
      related peptide (MIP-IR) was studied in two species of terrestrial snail: Helix
      lucorum L. and Eobania vermiculata L. Immunocytochemical staining with this
      antibody to MIP revealed 100-130 cells in the postcerebrum, located in two
      clusters with common pathways in the dorsal body nerve and the cerebral artery
      nerve. About 75% of the MIP-IR cells were labeled by backfilling of the dorsal
      body nerve in Helix and Eobania; the corresponding figures for labeling by
      backfilling of the cerebral artery nerve were about 60% in Helix and 30% in
      Eobania. Upon intracellular staining of neurons of the dorsomedial postcerebrum,
      where most of the MIP-IR cells were located, it was found that they projected
      either in the dorsal body nerve or in the cerebral artery nerve or in both. The
      obtained data suggest that growth and reproduction processes (both functions were
      attributed to the insulin-related peptide-containing neurons) are regulated by
      the two, partially coinciding subsets of postcerebral MIP-IR neurons with
      different types of branching.

PMID- 15490132
TI  - Human 3-D aVOR with and without otolith stimulation.
AB  - We describe in detail the frequency response of the human three-dimensional
      angular vestibulo-ocular response (3-D aVOR) over a frequency range of 0.05-1 Hz.
      Gain and phase of the human aVOR were determined for passive head rotations in
      the dark, with the rotation axis either aligned with or perpendicular to the
      direction of gravity (earth-vertical or earth-horizontal). In the latter case,
      the oscillations dynamically stimulated both the otolith organs and the semi
      circular canals. We conducted experiments in pitch and yaw, and compared the
      results with previously-published roll data. Regardless of the axis of rotation
      and the orientation of the subject, the gain in aVOR increased with frequency to
      about 0.3 Hz, and was approximately constant from 0.3 to 1 Hz. The aVOR gain
      during pitch and yaw rotations was larger than during roll rotations. Otolith and
      canal cues combined differently depending upon the axis of rotation: for
      torsional and pitch rotations, aVOR gain was higher with otolith input; for yaw
      rotations the aVOR was not affected by otolith stimulation. There was a phase
      lead in all three dimensions for frequencies below 0.3 Hz when only the canals
      were stimulated. For roll and pitch rotations this phase lead vanished with
      dynamic otolith stimulation. In contrast, the horizontal phase showed no
      improvement with additional otolith input during yaw rotations. The lack of a
      significant otolith contribution to the yaw aVOR was observed when subjects were
      supine, prone or lying on their sides. Our results confirm studies with less
      natural stimuli (off-vertical axis rotation) that the otoliths contribute a head
      rotation signal to the aVOR. However, the magnitude of the contribution depends
      on the axis of rotation, with the gain in otolith-canal cross-coupling being
      smallest for yaw axis rotations. This could be because, in humans, typical yaw
      head movements will stimulate the otoliths to a much lesser extent then typical
      pitch and roll head movements.

PMID- 15490133
TI  - Glycine-induced neurotoxicity in organotypic hippocampal slice cultures.
AB  - The role of the neutral amino acid glycine in excitotoxic neuronal injury is
      unclear. Glycine coactivates glutamate N-methyl-D-aspartate (NMDA) receptors by
      binding to a distinct recognition site on the NR1 subunit. Purely excitatory
      glycine receptors composed of NR1 and NR3/NR4 NMDA receptor subunits have
      recently been described, raising the possibility of excitotoxic effects mediated
      by glycine alone. We have previously shown that exposure to high concentrations
      of glycine causes extensive neurotoxicity in organotypic hippocampal slice
      cultures by activation of NMDA receptors. In the present study, we investigated
      further properties of in vitro glycine-mediated toxicity. Agonists of the glycine
      recognition site of NMDA receptors (D-serine and D-alanine) did not have any
      toxic effect in hippocampal cultures, whereas competitive blockade of the glycine
      site by 7-chlorokynurenic acid was neuroprotective. Stimulation (taurine, beta
      alanine) or inhibition (strychnine) of the inhibitory strychnine-sensitive
      glycine receptors did not produce any neurotoxicity. The toxic effects of high
      dose glycine were comparable in extent to those produced by the excitatory amino
      acid glutamate in our model. When combined with sublethal hypoxia/hypoglycemia,
      the threshold of glycine toxicity was decreased to less than 1 mM, which
      corresponds to the range of concentrations of excitatory amino acids measured
      during in vivo cerebral ischemia. Taken together, these results further support
      the assumption of an active role of glycine in excitotoxic neuronal injury.

PMID- 15490134
TI  - Visual acceleration and spatial distortion in right brain-damaged patients.
AB  - A subset of right brain-damaged patients shows leftward overextension in the line
      extension task. It has been argued that this deficit can be attributed to a
      distortion of the metric structure of perceived space (spatial anisometry). We
      investigated whether spatial distortion of static stimuli is associated with a
      corresponding misperception of perceived acceleration of moving stimuli. Seven
      right brain-damaged patients with spatial anisometry and two control groups were
      presented with stimuli moving leftwards or rightwards along the horizontal axis
      at different rates of acceleration. They were asked to estimate whether the
      target accelerated or decelerated. The anisometric group judged the perceived
      acceleration of leftward motions as less than that of rightward motions. The
      magnitude of the misperception of acceleration correlated positively with
      relative left overextension in the line extension task and with rightward
      displacement error in the line bisection task. This directional difference is in
      line with the predictions of the spatial anisometry hypothesis.

PMID- 15490135
TI  - Visual, haptic and crossmodal recognition of scenes.
AB  - Real-world scene perception can often involve more than one sensory modality.
      Here we investigated the visual, haptic and crossmodal recognition of scenes of
      familiar objects. In three experiments participants first learned a scene of
      objects arranged in random positions on a platform. After learning, the
      experimenter swapped the position of two objects in the scene and the task for
      the participant was to identify the two swapped objects. In experiment 1, we
      found a cost in scene recognition performance when there was a change in sensory
      modality and scene orientation between learning and test. The cost in crossmodal
      performance was not due to the participants verbally encoding the objects
      (experiment 2) or by differences between serial and parallel encoding of the
      objects during haptic and visual learning, respectively (experiment 3). Instead,
      our findings suggest that differences between visual and haptic representations
      of space may affect the recognition of scenes of objects across these modalities.

PMID- 15490136
TI  - Movement related potentials in acutely induced weakness and stroke.
AB  - Weakness is a common symptom of neurological illness, and recovery may occur via
      restorative or compensatory mechanisms. Functional imaging studies have shown
      varied patterns of activity in motor areas following recovery from stroke.
      Movement related potentials (MRP) reflect the activity in primary and non-primary
      motor areas. We recorded MRPs in association with index finger abduction in six
      normal volunteers before and after induced weakness of a hand muscle and in six
      stroke patients with subcortical lesions and weakness affecting the arm. In both
      groups of subjects the greatest change was observed in the motor potential
      component of the MRP. On average, the motor potential had its greatest amplitude
      and duration at the time of the greatest weakness and became smaller with
      recovery. In artificially-induced weakness, the MRP had an earlier onset latency
      (P=0.042) and a greater early BP component (P=0.05) for the weakened finger. For
      the stroke subjects overall, the peak and NS' amplitudes were largest for the
      initial study and declined thereafter. Similar but smaller changes were present
      for movements of the clinically unaffected side. The increased motor potential is
      therefore consistent with increased activity in the motor cortex, and this may
      occur as compensation for weakness in both normals and after stroke.

PMID- 15490137
TI  - Testing hypotheses and the advancement of science: recent attempts to falsify the
      equilibrium point hypothesis.
AB  - Criticisms of the equilibrium point (EP) hypothesis have recently appeared that
      are based on misunderstandings of some of its central notions. Starting from such
      interpretations of the hypothesis, incorrect predictions are made and tested.
      When the incorrect predictions prove false, the hypothesis is claimed to be
      falsified. In particular, the hypothesis has been rejected based on the wrong
      assumptions that it conflicts with empirically defined joint stiffness values or
      that it is incompatible with violations of equifinality under certain velocity
      dependent perturbations. Typically, such attempts use notions describing the
      control of movements of artificial systems in place of physiologically relevant
      ones. While appreciating constructive criticisms of the EP hypothesis, we feel
      that incorrect interpretations have to be clarified by reiterating what the EP
      hypothesis does and does not predict. We conclude that the recent claims of
      falsifying the EP hypothesis and the calls for its replacement by EMG-force
      control hypothesis are unsubstantiated. The EP hypothesis goes far beyond the EMG
      force control view. In particular, the former offers a resolution for the famous
      posture-movement paradox while the latter fails to resolve it.

PMID- 15490138
TI  - Accelerated recognition of left oblique views of faces.
AB  - Because faces in portraits are depicted more frequently in a left rather than a
      right oblique (half-profile or 3/4) view, we addressed the question of whether
      people find it easier to recognize the left or right 3/4 view of a familiar
      person's face. We examined the ability of 13 subjects to match familiar faces
      that were presented in either the left or right 3/4 view, with names that were
      presented either before or after the faces (face-name and name-face matching
      tasks, respectively). In both tasks, the subjects responded more rapidly to a
      left than to a right 3/4 view of the same face. This suggests that during face
      recognition the processing of information from faces that are presented in the
      left 3/4 view is dominant over the processing of right 3/4 views of familiar
      faces.

PMID- 15490139
TI  - Thyroid hormone responsive protein (THRP) mediates thyroid hormone-induced
      cytotoxicity in primary neuronal cultures.
AB  - The thyroid hormone responsive protein (THRP) is a novel gene product that
      remains responsive to thyroid hormone (TH) in the cerebral cortex of adult rats.
      To study the effects of THRP on neuronal cell survival, primary neurons cultured
      from rats at embryonic day 19 were treated with either 10(-7) mol L(-1) 3,5,3'
      triiodothyronine (T(3)), or 10(-7) mol L(-1) L: -thyroxine (T(4)). This resulted
      in decreasing neuronal cell number starting 48 h after treatment. T(3) -related
      cytotoxicity was also documented by measurement of lactate dehydrogenase release
      into the medium and by propidium iodide staining. Treatment of cells with 10(-7)
      mol L(-1) T(3) resulted in a significant increase in THRP mRNA levels as early as
      24 h of treatment in a concentration-dependent manner. T(3) treatment did not
      alter glyceraldehyde 3-phosphate dehydrogenase (G3PDH) mRNA levels. Exogenous
      expression of THRP by transfecting cells with a THRP expression construct (pSVL
      THRP) was associated with a significant increase in cell death as measured by the
      increased number of propidium iodide staining cells (18.0+/-2.1 cells per field)
      compared with mock-transfected cells (3.3+/-0.2), P<0.002. To further document
      THRP-induced cytotoxicity, the cells were either transfected with pSVL (empty
      vector)+pSV2neo (neomycin resistance vector for cell labeling), pSVL
      THRP+pSV2neo, or pSVL-THRP+pc-Abl (cAbl tyrosine kinase expressing
      vector)+pSV2neo. After 24 h the cells were treated with 500 microg mL(-1) G418 (a
      congener of neomycin) to eliminate the non-transfected cells. Transfection with
      pSVL-THRP reduced neuronal survival relative to cells transfected with pSVL
      (356+/-15.6 compared with 145+/-16.9, P<0.05). Co-transfection of THRP with wild
      type c-Abl did not alter the effect of THRP on cell survival. It is concluded
      that THRP is an important factor in TH-induced neuronal cell death.

PMID- 15490140
TI  - Atorvastatin effect on high-density lipoprotein-associated paraoxonase activity
      and oxidative DNA damage.
AB  - OBJECTIVE: High-density lipoprotein (HDL)-associated antioxidant paraoxonase
      (PON) may reduce low-density lipoprotein (LDL) oxidation and prevent
      atherosclerosis. The aim of this present study was to investigate the effect of
      the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor
      atorvastatin on hydrogen-peroxide-induced DNA damage by comet assay and the
      correlation between oxidative DNA damage and antioxidant PON activity. METHODS:
      Thirteen type-II/a hyperlipidemic patients were enrolled in the study. We
      examined the effect of 10 mg/day atorvastatin treatment on lipid levels and the
      degree of DNA damage in lymphocytes separated from hyperlipidemic patients,
      nitric oxide (NO), thiobarbituric acid-reactive substances (TBARS), PON levels
      and activity. RESULTS: After 6 months, atorvastatin treatment significantly
      decreased serum cholesterol and LDL-cholesterol levels. The triglyceride level
      did not change, and there was no significant change in the HDL cholesterol level.
      The visual score characteristic to the degree of DNA damage in comet assay was
      significantly decreased, as well as the TBARS level, while the level of NO was
      non-significantly increased. PON activity and the PON/HDL ratio were
      significantly increased after atorvastatin treatment. There was a negative
      correlation between DNA damage and PON activity, as well as between DNA damage
      and the PON/HDL ratio before and after atorvastatin treatment. CONCLUSION: These
      findings show that atorvastatin treatment favorably affected the lipid profile,
      increasing the activity of HDL-associated PON and decreasing the cytotoxic effect
      of oxidative stress.

PMID- 15490143
TI  - Clinical features determining the fate of a long-term, indwelling, forgotten
      double J stents.
AB  - We review our experiences with forgotten stents and investigate the potential
      factors determining the degree of encrustation. Our series consists of nine cases
      of forgotten stent that had remained indwelling for more than 1 year (mean 36.1
      months). We describe and compare their various clinical parameters in terms of
      encrustation. In addition, we briefly summarize our management schemes. All
      patients showed few stent related irritative symptoms. Six cases showing minimal
      or no encrustation shared the common feature of urine hypotonicity. Cystoscopic
      pullout was possible in these cases. The remaining three cases showed moderate to
      severe encrustation around the stent which required multiple procedures. Pyuria
      was observed in all cases and two patients had a history of urolithiasis.
      Finally, all cases were rendered stent and stone free. The fate of forgotten
      stents was dependent on the amount of encrustation around the stent. In our
      study, lithogenic history and presence of pyuria were associated with moderate to
      severe encrustation. Interestingly, patients showing urine hypotonicity tended to
      have a minimal encrustation on their stents and the stents were easily removed.
      Therefore, in patients with an impaired renal concentrating ability and a poor
      medical condition, the duration of indwelling stents might be safely prolonged if
      the patient has no risk factor for encrustation. As patients with forgotten
      stents are less likely to complain of stent related symptoms, thorough education
      of patients is important to prevent stent related complications.

PMID- 15490144
TI  - Primary alveolar capillary dysplasia (acinar dysplasia) and surfactant protein B
      deficiency: a clinical, radiological and pathological study.
AB  - BACKGROUND: Full-term infants with severe and prolonged respiratory distress
      represent a diagnostic challenge. Plain radiographic findings may be nonspecific
      or similar to classic surfactant deficiency disease for infants with surfactant
      protein B deficiency and acinar dysplasia. OBJECTIVES: To describe the similar
      clinical-radiolgical patterns of two rare neonatal conditions. MATERIALS AND
      METHODS: Six newborn babies with severe respiratory distress at birth
      demonstrated clinical and radiographically prolonged and progressive diffuse
      pulmonary opacification. RESULTS: All infants demonstrated hyperinflation of the
      lungs. The diffuse hazy opacification, which varied from mild (n=3) to moderate
      (n=3), progressed to severe diffuse opacification preceding death, which occurred
      at 12-36 days of life. Open lung biopsy confirmed the diagnosis of primary
      alveolar acinar dysplasia (AD) in four infants and surfactant protein B
      deficiency (SPBD) in two infants. CONCLUSIONS: In full-term babies with
      unexplained progressive respiratory distress from birth and progress of
      radiological changes, both AD and SPBD should be considered.

PMID- 15490145
TI  - Comparative imaging of differential pulmonary blood flow in patients with
      congenital heart disease: magnetic resonance imaging versus lung perfusion
      scintigraphy.
AB  - BACKGROUND: Lung perfusion scintigraphy is considered the gold standard to assess
      differential pulmonary blood flow while magnetic resonance (MR) has been shown to
      be an accurate alternative in some studies. OBJECTIVE: The purpose of the study
      was to assess the accuracy of phase contrast magnetic resonance (PC-MR) in
      measuring pulmonary blood flow ratio compared with lung perfusion scintigraphy in
      patients with complex pulmonary artery anatomy or pulmonary hypertension and to
      document reasons for discrepant results. MATERIALS AND METHODS: We identified 25
      cases of congenital heart disease between January 2000 and 2003, in whom both
      techniques of assessing pulmonary blood flow were performed within a 6-month
      period without an interim surgical or transcatheter intervention. The study group
      included cases with branch pulmonary artery stenosis, intracardiac shunts, single
      ventricle circulation, pulmonary venous anomalies and conotruncal defects. The
      mean age at study was 5.7 years (range 0.33-12) with a mean weight of 20.3 kg
      (range 6.5-53.6). The two methods were compared using a Bland-Altman analysis,
      and the Pearson correlation coefficient was calculated using the lung scan as the
      gold standard. Discrepant results were examined by reviewing the source images to
      elucidate reasons for error by MR. RESULTS: Bland-Altman analysis comparing right
      pulmonary artery (RPA) blood flow percentage, as measured by each modality,
      showed a mean difference of 1.43+/-9.8 (95% limits of agreement: -17.8, 20.6)
      with a correlation coefficient of r=0.84, P<0.0001. In six (24%) cases a large
      difference (>10%) was found with a mean difference between techniques of 17.9%.
      The reasons for discrepant results included MR artifacts, dephasing owing to
      turbulent flow, site of data acquisition and lobar lung collapse. CONCLUSION:
      When using PC-MR to assess pulmonary blood flow ratio, important technical errors
      occur in a significant proportion of patients who have abnormal pulmonary artery
      anatomy or pulmonary hypertension. If these technical errors are avoided, PC-MR
      is able to supply both anatomic and quantitative functional information in this
      patient population.

PMID- 15490146
TI  - Pre- and post-operative hydromyelia in spinal dysraphism.
AB  - BACKGROUND AND PURPOSE: There has been limited description of hydromyelia after
      surgery for spinal dysraphism. The opportunity to compare pre- and post-operative
      hydromyelia in patients with spinal dysraphism has been possible in two groups of
      patients using MRI. Post-operative assessment and possible relationship of
      hydromyelia to clinical findings has been made during a 7- to 14-year period.
      METHODS: A total of 38 patients with congenital lumbar or sacral lipomas and 20
      with diastematomyelia were studied pre-operatively with a 1.5-T MRI. Most
      patients in each group were examined with surveillance MRI (1.5 T) post
      operatively. Clinical correlations were carried out with each examination.
      RESULTS: Of the 38 dorsal or terminal lipoma post-operative patients, hydromyelia
      increased in 3 and was a new finding in 4. One symptomatic patient in the latter
      group had extensive septated lumbar hydromyelia. In 8 of 20 diastematomyelia
      patients, pre-operative hydromyelia was unchanged post-operatively. Hemicord
      hydromyelia developed in 1. CONCLUSION: Hydromyelia of varying degree was found
      in almost one-third of post-operative dorsal or terminal lipoma patients and
      nearly one-half of diastematomyelia patients. In five post-operative lipoma and
      two diastematomyelia patients, significant neurological findings remained. One of
      the six post-operative lipomas had new extensive lumbar hydromyelia that may have
      been responsible for the patient's symptoms. In the remaining symptomatic
      patients, hydromyelia was absent or modest.

PMID- 15490147
TI  - Morphometry of the corpus callosum in Chinese children: relationship with gender
      and academic performance.
AB  - BACKGROUND: The corpus callosum has been widely studied, but no study has
      demonstrated whether its size and shape have any relationship with language and
      calculation performance. OBJECTIVE: To examine the morphometry of the corpus
      callosum of normal Chinese children and its relationship with gender and academic
      performance. MATERIALS AND METHODS: One hundred primary school children (63 boys,
      37 girls; age 6.5-10 years) were randomly selected and the standardized academic
      performance for each was ascertained. On the mid-sagittal section of a brain MRI,
      the length, height and total area of the corpus callosum and its thickness at
      different sites were measured. These were correlated with sex and academic
      performance. RESULTS: Apart from the normal average dimension of the different
      parts of the corpus callosum, thickness at the body-splenium junction in the
      average-to-good performance group was significantly greater than the below
      average performance group in Chinese language (P=0.005), English language
      (P=0.02) and mathematics (P=0.01). The remainder of the callosal thickness showed
      no significant relationship with academic performance. There was no significant
      sex difference in the thickness of any part of the corpus callosum. CONCLUSIONS:
      These findings raise the suggestion that language and mathematics proficiency may
      be related to the morphometry of the fibre connections in the posterior parietal
      lobes.

PMID- 15490148
TI  - Can MRI replace DMSA in the detection of renal parenchymal defects in children
      with urinary tract infections?
AB  - BACKGROUND: Renal parenchymal defects may be a consequence of urinary tract
      infections (UTI) in childhood. MRI is a non-radiation imaging modality compared
      with DMSA scanning. OBJECTIVE: To compare DMSA with MRI for the detection of
      renal parenchymal defects in children presenting for radiological investigation
      after a first UTI. MATERIALS AND METHODS: Both DMSA and MRI were performed at the
      same appointment in 37 children (aged 4 months-13 years; mean 4.5 years) with a
      history of UTI. Both planar and SPECT DMSA were performed. MRI of the kidneys
      employed axial and coronal T1-, T2- and fat-saturated T1-weighted (T1-W)
      sequences. Some children had imaging after IV contrast medium. RESULTS: The
      coronal fat-saturated T1-W sequence was the best sequence and it detected all the
      findings on MRI. MRI had a sensitivity of 77% and a specificity of 87% for the
      detection of a scarred kidney using DMSA as the gold standard. MRI diagnosed
      pyelonephritis in two children that had been interpreted as scarring on DMSA.
      CONCLUSIONS: Renal MRI using a single, coronal, fat-saturated T1-W sequence is a
      rapid, accurate and minimally invasive technique for the detection of renal
      scarring that does not employ ionizing radiation.

PMID- 15490149
TI  - Gastrointestinal and renal abnormalities in cardio-facio-cutaneous syndrome.
AB  - Cardio-facio-cutaneous syndrome (CFC) is an uncommon autosomal recessive
      condition recently distinguished from Noonan syndrome but with more marked growth
      failure and ectodermal dysplasia. Abdominal symptoms are frequently described but
      anatomic lesions in CFC have rarely been described. We have found significant
      anatomic abnormalities in CFC patients including antral foveolar hyperplasia,
      severe constipation with fecal impaction, nephrocalcinosis and renal cysts.

PMID- 15490150
TI  - In vivo MRI measurement of blood oxygen saturation in children with congenital
      heart disease.
AB  - OBJECTIVE: The purpose of this prospective study was to measure in vivo blood
      oxygen saturation (%O2) by MRI in children with congenital heart disease (CHD)
      using population-based values for T2O (T2 signal decay of fully oxygenated blood)
      and K (a parameter representing the deoxyhemoglobin effect) and compare the %O2
      with direct cardiac catheterization measurements. BACKGROUND: MRI can determine
      %O2 using in vivo measurement of signal decay (T2) and an in vitro calibration
      curve relating T2 and %O2, based on the equation: 1/T2 = 1/T2O + K(1-%O2/100)2.
      Recent studies have correlated the T2/%O2 in children with CHD with the adult
      calibration statistics. METHODS: A total of ten children (five male, five female)
      with single ventricle CHD (median age 4.8 months, range 2 months to 4.4 years)
      undergoing cardiac catheterization were included in the study. The blood T2
      measurements for each patient were performed in a 1.5 T GE CV scanner. The %O2
      was then calculated based on the equation using values of T2O determined from
      individual hematocrits, and a population average value of K derived for children.
      The %O2 values were compared with direct %O2 measurements from cardiac
      catheterization. RESULTS: The %O2 values by MRI were strongly correlated with
      direct cardiac catheterization measurements (R = 0.825; P < 0.001). CONCLUSION:
      The study indicates that the noninvasive measurement of %O2 by MRI can accurately
      measure oxygen saturation in children with complex CHD.

PMID- 15490151
TI  - Gastrointestinal stromal tumour of the duodenum in a 7-year-old boy.
AB  - We report a 7-year-old boy presenting with an acute upper gastrointestinal (GI)
      haemorrhage subsequently diagnosed to have a very rare duodenal gastrointestinal
      stromal tumour (GIST). Endoscopy, pertechnetate and red cell scans were negative.
      Abdominal US detected a 17-mm mass lesion of the third part of the duodenum. This
      was confirmed on CT and shown to be hypervascular on selective angiography. At
      laparotomy, a 20-mm submucosal duodenal lesion was found associated with mucosal
      ulceration. Immunohistochemical analysis revealed it to be positive for CD117 (c
      KIT protein) consistent with a GIST. We emphasize the importance of a thorough
      abdominal US examination in children with GI haemorrhage and the consideration of
      GIST in the diagnosis after the common causes have been excluded.

PMID- 15490152
TI  - MRI reveals fetus in fetu in the mediastinum.
AB  - Fetus in fetu is an extremely rare condition in which a fetiform calcified mass
      is contained within the newborn or infant, often in the retroperitoneal cavity.
      We report a case of a fetus in fetu in the posterior mediastinum of a newborn.
      The prospective diagnosis was made by fetal US and MRI and confirmed by postnatal
      plain radiograph, CT and MRI.

PMID- 15490153
TI  - MICA response to gliadin in intestinal mucosa from celiac patients.
AB  - MHC class I chain-related gene A (MICA), a putative independent susceptibility
      gene in autoimmune diseases, encodes a surface protein present in epithelial
      cells that binds to NKG2D, an activating receptor of NK, alphabeta and gammadelta
      T cells, and could function as a stress-inducible activator of the innate immune
      response. There is no evidence of a long-term implication of MICA in the celiac
      autoimmune process. However, it could be that gliadin activation of MICA occurs
      only during the initial stages of the disease. In order to determine whether MICA
      is activated in response to gliadin in patients with celiac disease (CD), small
      intestinal mucosa biopsy samples from ten long-standing celiac patients on a
      gluten-free diet and from five non-celiac individuals were incubated with and
      without gliadin for 4 h. Total RNA was purified and MICA, IFNG and NKG2D mRNA
      were quantified by fluorescent real-time RT-PCR. Expression levels were
      calculated relative to GAPDH. MICA expression was detected in both patients and
      controls, but incubation with gliadin induced a strong increase in samples from
      the treated CD group compared with the non-CD controls (P=0.028), while no
      differences were observed for IFNG or NKG2D mRNA levels. The gliadin-provoked
      over-expression of MICA in "normalized" tissues from CD patients suggests a role
      for this stress-induced activator of the immune response in the early stages of
      organ-specific autoimmune destruction, probably preceding the onset of
      inflammation.

PMID- 15490155
TI  - Using Lactococcus lactis for glutathione overproduction.
AB  - Glutathione and gamma-glutamylcysteine were produced in Lactococcus lactis using
      a controlled expression system and the genes gshA and gshB from Escherichia coli
      encoding the enzymes gamma-glutamylcysteine synthetase and glutathione
      synthetase. High levels of gamma-glutamylcysteine were found in strains growing
      on chemically defined medium and expressing either gshA alone or both gshA and
      gshB. As anticipated, glutathione was found in a strain expressing gshA and gshB.
      The level of glutathione production could be increased by addition of the
      precursor amino acid cysteine to the medium. The addition of cysteine led to an
      increased activity of glutathione synthetase, which is remarkable because the
      amino acid is not a substrate of this enzyme. The final intracellular glutathione
      concentration attained was 358 nmol mg(-1) protein, which is the highest
      concentration reported for a bacterium, demonstrating the suitability of
      engineered L. lactis for fine-chemical production and as a model for studies of
      the impact of glutathione on flavour formation and other properties of food.

PMID- 15490154
TI  - Sequence and expression of C-type lectin receptors in Atlantic salmon (Salmo
      salar).
AB  - The diverse receptors of the C-type lectin superfamily play key roles in innate
      immunity. In mammals, cell surface receptors with C-type lectin domains are
      involved in pathogen recognition and in immune response, and in some cases are
      exploited by pathogens to gain entry into cells. This study reports on sequence
      and expression analysis of three paralogous group II C-type lectins from the
      teleost fish Atlantic salmon (Salmo salar). Each of the receptors showed
      similarity to immune-relevant mammalian receptors in terms of amino acid sequence
      and overall organization within the C-type lectin-like domain (CTLD). Two of the
      three have cytoplasmic motifs consistent with the immunoreceptor tyrosine-based
      activation motifs (ITAM), which are known to modulate downstream functions in
      leukocytes. All three C-type lectin receptors were expressed in multiple tissues
      of healthy fish, including peripheral blood leukocytes and salmon head kidney
      cells (SHK-1). Each receptor was up-regulated in salmon liver in response to
      infection by Aeromonas salmonicida and one receptor was substantially up
      regulated in cultured SHK-1 cells in response to lipopolysaccharide (LPS).
      Putative binding sites for the CAAT-enhancer-binding protein (C/EBP) family of
      transcription factors in the regulatory regions of these C-type lectin genes may
      mediate their response to bacteria and LPS in salmon leukocytes. The
      identification of these types of receptors in distinct populations of cells
      within the immune system will provide important markers for identifying and
      categorizing the state of differentiation or activation of these cells and lead
      to further understanding of the interaction between the salmon host and multiple
      pathogens.

PMID- 15490156
TI  - Cloning, expression, and characterization of a glycoside hydrolase family 86 beta
      agarase from a deep-sea Microbulbifer-like isolate.
AB  - The gene for a novel beta-agarase from a deep-sea Microbulbifer-like isolate was
      cloned and sequenced. It encoded a mature protein of 126,921 Da (1146 amino
      acids), which was a modular protein including two tandem carbohydrate-binding
      module (CBM)-like sequences and a catalytic module. The catalytic module
      resembled a glycoside hydrolase family 86 beta-agarase, AgrA, from
      Pseudoalteromonas atlantica T6c with 31% amino acid identity. Its recombinant
      agarase was hyper-produced extracellularly using Bacillus subtilis as the host
      and purified to homogeneity. The activity and stability were strongly enhanced by
      CaCl2. The maximal enzyme activity was observed at 45 degrees C and pH 7.5 in the
      presence of 10 mM CaCl2. The enzyme was an endo-type beta-agarase and degraded
      agarose and agarose oligosaccharides more polymerized than hexamers to yield
      neoagarohexaose as the main product. This is the first glycoside hydrolase family
      86 enzyme to be homogeneously purified and characterized.

PMID- 15490158
TI  - Reductive transformation of TNT by Escherichia coli: pathway description.
AB  - The reductive transformation of 2,4,6-trinitrotoluene (TNT) was studied using
      aerobically grown Escherichia coli cultures. In the absence of an external carbon
      or energy source, E. coli resting cells transformed TNT to
      hydroxylaminodinitrotoluenes (2HADNT, 4HADNT, with 4HADNT as the dominant
      isomer), aminodinitrotoluenes (4ADNT, with sporadic detection of 2ADNT), 2,4
      di(hydroxylamino)-6-nitrotoluene (24D(HA)6NT), 2,4-diamino-6-nitrotoluene
      (24DA6NT), and an additional compound which was tentatively identified as a
      (hydroxylamino)aminonitrotoluene isomer via gas chromatography/mass spectroscopy
      and spectral analysis. The resting cell assay, performed in an oxygen-free
      atmosphere, avoided formation of azoxy dimers and provided good mass balances.
      Significant preference for reduction in the para versus ortho position was
      detected. The formation of 24D(HA)6NT, but not ADNT, appeared inhibited by the
      presence of TNT. The rate and extent of TNT reduction were significantly enhanced
      at higher cell densities, or by supplying an exogenous reducing power source,
      revealing the importance of enzyme concentration and reducing power. Whether the
      oxygen-insensitive E. coli nitroreductases, encoded by nfsA and nfsB, directly
      catalyze the TNT reduction or account for the complete TNT transformation
      pathway, remains to be determined.

PMID- 15490159
TI  - Giant fatty Schmorl's nodes: CT findings in four patients.
AB  - OBJECTIVE: To describe the CT features of an unusual type of lumbar Schmorl's
      node (SN) appearing as giant fatty lesion of the vertebral bodies. DESIGN AND
      PATIENTS: >Four patients (4 men; mean age 48.5 years) collected during a 9-month
      period were examined with MDCT for unremarkable lumbar symptoms; none had
      relevant history of specific trauma during the last years preceding the CT.
      RESULTS AND CONCLUSIONS: The CT findings had a similar showing: a central or para
      central osteolytic lesion in contact with the upper end plate of the vertebra,
      occupying about two-thirds to three-quarters of the body height and being
      surrounded by a thin and well-delineated bony rim. There was a clear interruption
      of the superior vertebral end plate above the lesion and an almost normal height
      of the adjacent vertebral disk. The CT appearance suggested a uniform fat content
      which was confirmed by density measurements ranging from -20 to -30 HU. The
      origin remains unknown, but a parallel is drawn between giant fatty SNs and giant
      cystic SNs. Intravertebral disk herniation is likely to be the initial
      phenomenon, with a preponderant responsibility of the "secondary induced
      intramedullar tissular disorders" to constitute the final size of the lesion. One
      hypothesis could be a fracture of trabecular bone with secondary hemorrhage and
      cystic or fatty degeneration. Alternatively, intramedullary vascular disturbances
      may lead to foci of bone necrosis that heal by fibroblastic proliferation
      followed by mucoid or fatty degeneration. It is also possible that giant fatty
      SNs could represent end stage of giant cystic SNs.

PMID- 15490160
TI  - Magnetic resonance imaging of the wrist in rheumatoid arthritis: demonstration of
      progression between 1 and 6 years.
AB  - OBJECTIVE: To describe the changes seen in the wrist in rheumatoid arthritis (RA)
      on magnetic resonance (MR) imaging obtained at 1 year and 6 years. DESIGN: A
      cohort of patients with RA has been studied prospectively from symptom onset.
      PATIENTS: MR scans of the dominant wrist in 31 patients obtained at 1 year and 6
      years were compared for bone erosions, marrow signal change (oedema), synovial
      thickness and tenosynovitis. RESULTS: Twenty-two patients had an increase in
      erosion score in the interval and three patients showed a decrease in erosion
      score suggesting erosion healing. Fourteen patients had an increase in oedema
      score in the interval and eight patients had a decrease in oedema score. Synovial
      thickness increased in 13 patients and decreased in eight. Tenosynovitis
      increased in 15 patients and decreased in five. Bone erosions developed
      immediately adjacent to the tenosynovitis in two patients. CONCLUSIONS: MR
      imaging is useful in following the progress of bone erosions, marrow oedema,
      synovitis and tenosynovitis in RA.

PMID- 15490162
TI  - Radiographic evaluation of the Duraloc cup after 4 years.
AB  - We implanted 71 metal-backed, porous-coated, hemispheric, press-fit Duraloc-100
      cups in 68 consecutive patients. In 61 patients, the femoral stem was a
      cementless Spotorno and in ten a cemented Lubinus SP II. A 28-mm Biolox ceramic
      head was used with both stems. After an average follow-up of 4 (3.7-5.9) years,
      we examined 67 hips. Radiolucencies were described in three zones according to
      DeLee and Charnley, and migration was measured on serial radiographs using the
      computer-assisted EBRA method. Total migration of more than 1 mm within the first
      2 years occurred in 22/62 cups. Nine cups showed more than 1.5 mm total migration
      within the first 2 years and more than 2 mm within the whole period. The presence
      of post-operative radiolucencies correlated significantly with a total migration
      value of more than 2 mm within the first 2 years (p=0.02). Post-operative
      radiolucencies in zone 1 correlated with a total migration value of more than 2
      mm within the first 2 years (p=0.027) and more than 2.5 mm within the whole
      period (p=0.051). These correlation values might reflect the quality of operative
      technique, particularly reaming, and implant selection.

PMID- 15490163
TI  - Osteomyelitis in Polynesian children.
AB  - Polynesians, including New Zealand Maori, are known to be prone to bacterial
      infections. We studied 85 New Zealand children with osteomyelitis requiring
      admission in a tertiary care hospital in a 2-year period in order to attain
      information regarding incidence and relative risk. During the observation period,
      the hospital was responsible for the healthcare of a total population of 103,900
      children per annum. An increased relative risk of Polynesian and Maori children
      to suffer from osteomyelitis was calculated to be 3.84. The major pathogenic
      organism was Staphylococcus aureus. Complications such as extension to adjacent
      joints or sepsis were a rather rare occurrence. Further research is required to
      identify whether genetic predisposition or social and environmental circumstances
      are involved in this phenomenon.

PMID- 15490164
TI  - Comparison of traditional and intrafascial iliac crest bone-graft harvesting in
      lumbar spinal surgery.
AB  - We studied 117 adult patients undergoing posterior lumbar spinal fusion and
      instrumentation using bone grafts from the iliac crest between February 1999 and
      January 2001. All patients had degenerative disease of the lumbar spine, and all
      were operated upon by the same surgeon. Patients were randomized to have the
      iliac bone graft harvested either through a separate incision (traditional
      approach) or utilizing the same midline incision as used for the spinal surgery
      (intrafascial approach). Total volume of harvested graft, blood loss, pain,
      complications, and patient satisfaction were evaluated with a minimum of 2-year
      follow-up. There were no infections. The average volume of harvested bone was
      17.2 cc versus 14.7 cc; total blood loss was 168 cc versus 96 cc; total
      complication rate was 20% versus 8%, and overall satisfaction rate was 81% versus
      96%, respectively. The intrafascial graft harvesting technique minimizes
      morbidity and increases patient satisfaction compared with the traditional bone
      harvesting technique.

PMID- 15490165
TI  - Inhibition of HUVEC tubulogenesis by hederacolchiside-A1 is associated with
      plasma membrane cholesterol sequestration and activation of the Ha-Ras/MEK/ERK
      cascade.
AB  - PURPOSE: Neoangiogenesis is critical to cancer proliferation and metastasis and
      constitutes an attractive target for cancer therapy. It has previously been
      demonstrated that hederacolchiside-A1 (HCol-A1), a triterpenoid saponin from
      Hedera colchica Koch, has antimelanoma potential. The goal of this study was to
      evaluate, in vitro, if in addition to its tumoricidal effect on melanoma cells,
      HCol-A1 might affect endothelial cell network formation. METHODS: We investigated
      whether HCol-A1 affects matrigel-induced tubulogenesis and inhibits the viability
      (WST-1 assay) of human umbilical vein endothelial cells (HUVECs). To provide
      structure-activity relationships (SAR), studies were conducted on HCol-A1,
      oleanolic acid and hederacolchiside A (HCol-A), a triterpenoid saponin which
      possess the same sugar sequence as Hcol-A1. Plasma membrane cholesterol
      sequestration was studied by labelling with [3H]cholesterol and assayed with HCol
      A1-cholesterol complexes. HCol-A1 signalling was investigated using immunoassays.
      RESULTS: In contrast to HCol-A and oleanolic acid, HCol-A1 inhibited matrigel
      induced angiogenesis at micromolar concentration. Plasma membrane cholesterol
      sequestration was found to be critical for this activity. Activation of the
      Ras/MEK/ERK cascade appears to be one of the mechanisms by which Hcol-A1 affects
      HUVEC network formation. The predominant activation of the Ha-Ras isoform, which
      decreases HUVEC-tolerance to apoptosis, might contribute to the high
      susceptibility of this cell line to HCol-A1. CONCLUSION: Since cholesterol
      sequestration affects cell confluence-dependent remodelling of endothelial
      membranes and vascular endothelial growth factor receptor-2 activity, these
      results raise the possibility that Hcol-A1 might slow-down cancer proliferation
      and metastasis in vivo by inhibiting critical aspects of neoangiogenesis. Further
      in vivo studies are needed to verify this hypothesis.

PMID- 15490166
TI  - Improved potency of cisplatin by hydrophobic ion pairing.
AB  - Cisplatin is one of the most widely used and effective chemotherapeutic drugs
      ever discovered against certain forms of cancer. However, its use is limited by
      toxicity. A more potent form might allow lower doses to be used and would
      diminish the toxicity. A new analog of cisplatin has been synthesized by
      stoichiometric replacement of the chloride ligands with the anionic surfactant,
      Aerosol OT (AOT). The new compound has a very low aqueous solubility (about 2
      mg/l) and a log P value of 2.17, which is more than 4 log units higher than
      cisplatin itself, indicating a dramatic increase in hydrophobicity. While
      hydrophobic cisplatin analogs have been synthesized previously, this is the first
      one with readily dissociable ligands replacing the chlorides. The resultant AOT
      complex is able to penetrate cellular membranes more efficiently, resulting in a
      threefold to fivefold increase in intracellular platinum levels. These increased
      intracellular concentrations correlate with lower IC50 values in a number of
      cancer and normal cell lines. These findings suggest that further development of
      the AOT complex as a chemotherapeutic agent is warranted, given its marked
      increase in potency over the parent compound.

PMID- 15490171
TI  - [The 11th Baltic-German Symposium in Tallin, Estonia].

PMID- 15490172
TI  - [Schistosomiasis in a leiomyoma of the uterus].
AB  - This case report deals with an, in our regions, unusual diagnosis of coincidence
      of a genital schistosomiasis of a 30-year-old woman, coming from Africa. The
      female patient presented herself by a specialist because of longer lasting
      hypermenorrhoe. After clinical examination the patient underwent an operation
      because of an uterus myomatosus. The histopathological evaluation showed beside a
      leimyoma an expanded infestation with schistosomiasis haematobium. After
      pathological diagnosis the patient underwent the standard therapy with a single
      injection of praziquantel. We report about the clinic, epidemiology, morphology
      and diagnostic.

PMID- 15490174
TI  - Questions on the superiority of alfacalcidol over plain vitamin D in the
      treatment of glucocorticoid-induced osteoporosis.

PMID- 15490173
TI  - Activity of the yeast Tat2p tryptophan permease is sensitive to the anti-tumor
      agent 4-phenylbutyrate.
AB  - 4-Phenylbutyrate (PB) induces differentiation and is being intensively studied as
      a treatment for brain, prostate, breast, and hematopoietic cancer. While many
      different primary targets for PB have been proposed, the mechanism by which it
      causes cellular differentiation remains unknown. To identify the primary cellular
      target, we investigated its effects on Saccharomyces cerevisiae and showed that
      it inhibits tryptophan transport. We show here that PB and sorbic acid induce an
      ubiquitin-dependent turnover of the tryptophan permease Tat2p. However, the
      inhibition of transport is not a consequence of the loss of Tat2p, since it also
      occurs when turnover is prevented by deleting the Tat2p ubiquitination sites.
      When we tested the effects of PB and other growth inhibitory agents on the growth
      of amino acid auxotrophs, we found that several auxotrophs are hypersensitive to
      a number of chemically unrelated agents, including PB and some, but not all, weak
      acids; and this sensitivity is due to the inhibition of amino acid transport. For
      the inhibitory weak acids, inhibition is not confined to aromatic amino acid
      auxotrophs, nor is it a general weak acid stress response, since the degree of
      inhibition is independent of weak acid hydrophobicity and p Ka. Our results show
      that diverse agents affect the activity of the Tat2p permease rather than its
      stability and suggest the hypothesis that the anti-neoplastic action of PB is due
      to a decrease in the activity of surface receptors or other membrane proteins
      needed to maintain the transformed state.

PMID- 15490175
TI  - Unusual presentation of lupus nephritis.
AB  - We report a male patient who presented with pyrexia, generalized lymphadenopathy,
      hepatosplenomegaly, and pleural effusion with no cutaneous or musculoskeletal
      symptoms. Despite extensive investigation, no cause was detected. His initial
      serology was also negative for autoantibodies. The patient was placed on a trial
      of antitubercular treatment in view of a positive Mantoux test. His disease
      evolved into the full clinical picture of systemic lupus erythematosus with
      nephritis (World Health Organisation class IV) and strongly positive antinuclear
      antibody and dsDNA over a period of months. He was treated successfully with
      intravenous cyclophosphamide pulses along with oral prednisolone, and the disease
      was still in remission after 3 years of follow-up.

PMID- 15490176
TI  - Visualisation of non-invasive coronary bypass imaging: 4-row vs. 16-row
      multidetector computed tomography.
AB  - The purpose of this study was to investigate the image quality of coronary artery
      bypass graft visualization in 4- and 16-row multidetector CT using multiple
      imaging reformations. MATERIAL AND METHODS: One hundred sixteen patients
      underwent CT examination of the heart after receiving CABG. Group A (n=58)
      received 4-row MDCT; group B (n=58) received 16-row MDCT. Various bypass types
      such as LITA to LAD and venous grafts to the RCA and RCX were included in the
      study. A five-point Likert scale was used to grade image quality. Each bypass was
      reviewed under different imaging reformations: thin slap maximum intensity
      projection (MIP thin), multiplanar reformation (MPR) and volume rendering
      technique (VRT). Special attention was paid to the delineation of the distal
      anastomosis. Interobserver correlation was determined. RESULTS: From 289 bypass
      grafts examined, 279 (96.54%) were classified as patent and 10 (3.46%) as not
      patent. Except for the distal anastomosis, 16-row MDCT showed significantly
      better results for all segments of bypasses. Comparison of reformations within
      group A and B showed that MIP thin (P<0.05) and VRT (P<0.05) displayed better
      visualization as compared to MPR. CONCLUSION: Significantly better imaging of all
      bypass types is possible using 16-row MDCT as compared to 4-row MDCT. Assessment
      of the distal anastomosis yields no difference between 4- and 16-row technology.

PMID- 15490177
TI  - Imaging of the complications of laparoscopic cholecystectomy.
AB  - Laparoscopic cholecystectomy has, in recent years, emerged as the gold standard
      therapeutic option for the management of uncomplicated symptomatic
      cholelithiasis. Each year, up to 700,000 of these procedures are performed in the
      United States alone. While the relative rate of post-procedural complications is
      low, the popularity of this method of gallbladder removal is such that this
      entity is not uncommonly clinically encountered, and therefore must be borne in
      mind by the investigating physician. By way of pictorial review, we explore the
      radiological appearances of a variety of potential complications of laparoscopic
      cholecystectomy. The radiological appearances of each shall be illustrated in
      turn using several imaging modalities, including ultrasound, computed tomography,
      MR cholangiography and radio-isotope scintigraphy. From calculus retention to
      portal vein laceration, bile duct injury to infected dropped calculi, we
      illustrate numerous potential complications of this procedure, as well as
      indicating the most suitable imaging modalities available for the detection of
      these adverse outcomes. As one of the most commonly performed intra-abdominal
      surgeries, laparoscopic cholecystectomy and the complications thereof are not
      uncommonly encountered. Awareness of the possible presence of these numerous
      complications, including their radiological appearances, makes early detection
      more likely, with resultant improved patient outcome.

PMID- 15490178
TI  - Automated mass detection in contrast-enhanced CT colonography: an approach based
      on contrast and volume.
AB  - The purpose of this feasibility study was to design and test an algorithm for
      automating mass detection in contrast-enhanced CT colonography (CTC). Five
      patients with known colorectal masses underwent a pre-surgical contrast-enhanced
      (120 ml volume 1.6 g iodine/s injection rate, 60 s scan delay) CTC in high
      spatial resolution (16-slice CT: collimation: 16x0.75 mm, tablefeed: 24 mm/0.5 s,
      reconstruction increment: 0.5 mm). A CT-density- and volume-based algorithm
      searched for masses in the colonic wall, which was extracted before by segmenting
      and dilating the colonic air lumen and subtracting the inner air. A radiologist
      analyzed the detections and causes of false positives. All masses were detected,
      and false positives were easy to identify. Combining CT density with volume as a
      cut-off is a promising approach for automating mass detection that should be
      further refined and also tested in contrast-enhanced MR colonography. More
      information under http://www.screening.info.

PMID- 15490179
TI  - Multislice CT imaging of anomalous coronary arteries.
AB  - The purpose of the present study was to evaluate the role of 16 multislice
      computed tomography (MSCT) to identify the origin of anomalous coronary arteries
      and to confirm their anatomic course in relation to the great vessels. Accuracy
      of coronary artery disease (CAD) detection was a secondary aim and was tested
      with conventional angiograms (CA) serving as standard of reference. Two hundred
      and forty-two consecutive patients referred for noninvasive coronary CT imaging
      were reviewed for the study. Sixteen patients (6.6%) with anomalous coronary
      arteries were detected and included as the study group. MSCT and CA images were
      analyzed in a blinded fashion for accuracy of anomalous artery origin and path
      detection. Results were compared in a secondary consensus evaluation. Accuracy
      ratios to detect CAD with MSCT in all vessels were calculated. Coronary anomalies
      for all 16 patients were correctly displayed on MSCT. CA alone achieved correct
      identification of the abnormality in only 53% (P=0.016). Sensitivity and
      specificity of MSCT to detect significantly stenosed vessels was 90 and 92%. 16
      MSCT is accurate to delineate abnormally branching coronary arteries and allows
      sufficiently accurate detection of obstructive coronary artery disease in distal
      branches. It should therefore be considered as a prime non-invasive imaging tool
      for suspected coronary anomalies.

PMID- 15490180
TI  - Detection of dysbaric osteonecrosis in military divers using magnetic resonance
      imaging.
AB  - This was a controlled cross-sectional study to investigate the prevalence of
      dysbaric osteonecrosis (DON) in military divers. MRI examinations of the large
      joints and adjacent bones were performed in a cross-sectional group of 32 highly
      experienced military divers and 28 non-divers matched for age and anthropometric
      data. Additional plain radiographs and follow-up controls were performed in all
      persons with signs certain or suspicious of DON. In two subject groups (one of
      divers and one of non-divers), lesions characteristic of DON were detected. From
      this controlled study, it may be concluded that MRI is a highly sensitive method
      to detect signs of osteonecrosis. It could be shown that the prevalence of bone
      lesions characteristic of osteonecrosis in highly experienced military divers is
      not higher than in non-diving subjects of comparable age. The outcome of this
      comparably small study group fits to the results of previous extensive studies
      performed with radiographs. The detected low incidence of DON in this collective
      may be due to the fact that military divers follow stricter selection criteria,
      decompression schemes and medical surveillance than commercial divers.

PMID- 15490181
TI  - High-flow priapism: colour-Doppler ultrasound-guided supraselective embolization
      therapy.
AB  - High flow priapism is mainly caused by traumatic arteriocavernous fistulas. The
      standard therapy is a transcatheter embolization of the fistula. This study
      analyzes the combined approach of arteriography and color Doppler ultrasound
      during the embolization procedure. During the arteriography procedure, a perineal
      color Doppler ultrasound examination of the fistula was performed to achieve an
      optimal positioning of the catheter tip in the fistula with a minimum of
      radiation exposure. To visualize the correct localization, ultrasound contrast
      medium or saline solution was injected through the catheter. The flow-pattern of
      the contrast medium allowed evaluation of the successful occlusion of the fistula
      and preservation of the unaffected penile arteries. In six patients (unilateral
      fistula: three, bilateral fistulas: three) with a posttraumatic high-flow
      priapism, this technique was performed for embolization of the fistulas. A total
      of nine embolization sessions were performed. Only one case required a second
      session due to dislocation of a microcoil. In all cases, the priapism disappeared
      immediately after the final session while erectile function was restored within 4
      weeks after embolization. The combined approach of x-ray and ultrasound imaging
      facilitates the supraselective embolization of the arteriocavernous fistula,
      leading to an optimal success rate, while reducing the radiation exposure and the
      applied dose of contrast medium.

PMID- 15490182
TI  - [Patient characteristics in a tertiary glaucoma center. Circumstances of
      treatment and attitudes of patients].
AB  - BACKGROUND: In order to look for conceptual improvements in the practical
      management of patients sent to our glaucoma department, we analyzed the
      structures, behaviour, and knowledge about the disease in this patient group.
      METHODS: Glaucoma patients who were sent for the first time to our department
      were included prospectively. Before being examined 129 patients were asked to
      answer a questionnaire concerning their individual characteristics, their
      behaviour, and patterns of treatment. RESULTS: Of the patients 74% had open-angle
      glaucoma (including normal tension, exfoliative, and pigment glaucoma), 22% had
      secondary glaucoma (including neovascular, congenital, and chronic closed-angle
      glaucoma), and 4% had suspected glaucoma. Written documentation of previously
      performed intraocular pressure measurements was not available for 84% of the
      patients. Younger patients had significantly more knowledge about glaucoma and
      used more possibilities to get information about the disease than elder patients.
      CONCLUSION: Education about glaucoma disease should be optimized especially for
      elder glaucoma patients. Documentation of intraocular pressure measurements is
      insufficient in our patient group.

PMID- 15490183
TI  - [Ischemia and hypoxia. An attempt to explain the different rates of retinal
      ganglion cell death in glaucoma].
AB  - In hypoxic or ischemic states, the receptors of the ganglion cells are
      overstimulated by release of neurotransmitters. Glutamate and GABA (gamma
      aminobutyric acid) are the decisive neurotransmitters in the retina. It is
      presumed that the extent of cell death depends on the degree of depolarization,
      which in turn is determined by the amount of excitatory (glutamate) or inhibitory
      (GABA) receptors of the corresponding ganglion cell. The assumption is that the
      receptor profile of the individual ganglion cells determines the sensitivity of
      these cells to hypoxia or ischemia, i.e., the time up to cell death, and thus
      represents the underlying cause of the different rates of cell death in primary
      chronic open-angle glaucoma. Research on this receptor profile could be of
      pivotal importance for the approach to neuroprotective treatment of primary
      chronic open-angle glaucoma.

PMID- 15490184
TI  - [Mechanisms of neuroprotection against glaucoma].
AB  - The goal of neuroprotection in glaucoma treatment is to employ agents that
      prevent or delay apoptosis of retinal ganglion cells (RGC) and facilitate
      regeneration of already damaged calls. The following contribution discusses the
      mechanisms of RGC death and current status of neuroprotective in vivo studies and
      investigations on cell cultures and animal models. Discussions on the
      etiopathogenesis of PCOAG center on elevated IOP and ocular disorders of vascular
      function. The mechanisms of axonal damage induced by ischemia are explained and
      the resultant possible neuroprotective effect mechanisms are discussed (Na(+) or
      Ca(2+) channel blockers, role of reactive astrocytes). Substitution of axonal
      survival factors and especially the role of BDNF are described. Glutamate
      excitotoxicity also plays a role in glaucomatous antegrade RGC death. Relevant
      questions and possible therapeutic approaches are discussed. The three phases of
      apoptosis cascade and the key role of mitochondria in the insult-induced
      apoptosis are considered as well as the still relatively unexplored possibilities
      of RGC regeneration. Finally, perspectives of neuroprotective treatment of PCOAG
      are presented.

PMID- 15490185
TI  - [Neuroprotection against glaucoma remains a concept].
AB  - According to estimates made by WHO, approximately 105 million people are affected
      worldwide by glaucoma. This can be defined as progressive optic neuropathy with
      structural damage of the optic nerve head and death of retinal ganglion cells.
      Although elevated IOP is considered responsible for glaucoma, lowering the
      pressure often does not result in improvement. For this reason, other etiological
      factors are presumed, which are presented in the following contribution. The role
      of neuroprotective agents in the treatment of glaucoma is discussed. The pattern
      of ganglion cell death specific to glaucoma seems to suggest that certain
      ganglion cells could be more sensitive than others. The theory of "cumulative
      damage" in this case includes the hypothesis that the delayed onset of many
      neurodegenerative diseases such as glaucoma, Alzheimer's disease, or Parkinson's
      disease can be attributed to the age-related accumulation of toxic substances in
      the ganglion cells. On the contrary, the theory of "singular damage" is based on
      the assumption that certain ganglion cells are in a state of reduced homeostasis
      caused by the expression of so-called mutant response genes. Therapeutic
      approaches worthy of consideration based on their side effect profile and
      efficacy in animal trials, are presented.

PMID- 15490186
TI  - [Acute visual deterioration after "alternative therapy" in Russia].

PMID- 15490187
TI  - [Frankfurt-Freiburg Contrast and Acuity Test System (FF-CATS). A new test to
      determine contrast sensitivity under variable ambient and glare luminance
      levels].
AB  - BACKGROUND: The purpose of the present study was to evaluate a computerized test
      for measurement of contrast sensitivity thresholds under variable ambient and
      glare luminance levels. METHODS: A total of 40 eyes of 40 healthy subjects were
      examined with the FF-CATS and the Functional Acuity Contrast Test (FACT) at 0.167
      cd/m(-2) (mesopic) and 167 cd/m(-2) (photopic). Measurements were performed twice
      with and without glare in a randomized fashion. Tests were evaluated according to
      three criteria: (1) repeatability, (2) discriminative ability, and (3) validity.
      RESULTS: The FF-CATS showed a higher discriminative ability between the two
      groups compared to the FACT charts. Under photopic conditions, the COR value was
      0.39 for the FF-CATS and 0.26 for the FACT charts; under mesopic illumination,
      the COR value for the FF-CATS was 0.46 and 0.36 for the FACT charts. CONCLUSION:
      The FF-CATS is a reliable, sensitive, valid, and flexible test system for the
      determination of visual acuity and contrast sensitivity thresholds under variable
      ambient and glare luminance conditions.

PMID- 15490188
TI  - [cSLO digital fundus autofluorescence imaging].
AB  - BACKGROUND: Fundus autofluorescence (FAF) originates from age- and disease
      dependent accumulation of lipofuscin in the lysosomal compartment of the retinal
      pigment epithelium (RPE). FAF imaging is a noninvasive method to detect intrinsic
      RPE fluorescence in vivo. We describe features of a novel confocal scanning laser
      ophthalmoscope (cSLO) for FAF imaging and compare images to the previous cSLO
      system. METHODS: FAF images were obtained with a cSLO using an optically pumped
      solid state laser (OPSL) instead of an argon laser for generation of excitation
      light at 488 nm. For detection of emitted FAF signals >500 nm a barrier filter
      was used. RESULTS: The novel cSLO allows FAF imaging with a resolution of up to 5
      microm/pixel to delineate normal and pathological features in various retinal
      pathologies including early-stage and advanced atrophic or neovascular age
      related macular degeneration, macular edema, and retinal dystrophies. Further
      technical improvements include an internal fixation target and an enlarged
      optical focus adaption range. CONCLUSIONS: Improved image quality using the novel
      cSLO for FAF imaging is of clinical relevance for diagnosis and precise
      phenotyping of retinal diseases. This method may also be useful to monitor
      therapeutic effects targeting RPE lipofuscin accumulation as a common
      pathogenetic pathway in various degenerative and hereditary retinal diseases.

PMID- 15490189
TI  - [Acute monocular vision reduction in a pregnant patient].

PMID- 15490190
TI  - Nature as a model for technical sensors.
AB  - Nature has developed a stunning diversity of sensory systems. Humans and many
      animals mainly rely on visual information. In addition, they may use acoustic,
      olfactory, and tactile cues for object detection and spatial orientation. Beyond
      these sensory systems a large variety of highly specialized sensors have evolved.
      For instance, some buprestid beetles use infrared organs for the detection of
      forest fires. The infrared sensors of boid and crotalid snakes are used for prey
      detection at night. For object detection and spatial orientation many species of
      nocturnal fish employ active electrolocation. This review describes certain
      aspects of the detection and processing of infrared and electrosensory
      information. We show that the study of natural exotic sensory systems can lead to
      discoveries that are useful for the construction of technical sensors and
      artificial control systems. Comparative studies of animal sensory systems have
      the power to uncover at least a small fraction of the gigantic untapped reservoir
      of natural solutions for perceptive problems.

PMID- 15490191
TI  - MRI for the management of neonatal cerebral infarctions: importance of timing.
AB  - PURPOSE: Focal ischemic stroke in neonates is a rare occurrence. Diagnosis with
      most imaging modalities is difficult, but necessary for initiating an
      anticoagulatory treatment. The purpose of this study was to evaluate the
      sensitivity of MRI sequences within the first 14 days of birth. PATIENTS AND
      METHODS: Four patients with neonatal stroke presenting as seizures were examined
      using a standard MRI protocol including diffusion-weighted images (DWI) and
      magnetic resonance angiography (MRA) within 72 h of birth. The time between the
      onset of symptoms and MRI ranged from 6 h to 48 h. Follow-up examinations were
      performed on days 5 ( n=1), 7 ( n=2), and 14 ( n=1) for the control of a
      treatment with low-molecular heparin. RESULTS: Eight infarctions were detected in
      the four patients, 5 in the middle cerebral artery (MCA), three in the posterior
      cerebral artery (PCA) territory. All lesions were visible using DWI, four on T2
      weighted images. Whereas in two patients small lesions contralateral to a large
      stroke were missed on T2-weighted images, the diagnosis would have been missed
      altogether without DWI in one patient. On follow-up, the visibility of the
      infarctions had declined using DWI after 5 days and the lesions were invisible
      after 1 week. Fourteen days after the stroke, an increased diffusion was detected
      in the infarcted brain tissue. By this time, all lesions were visible on T2
      weighted images. CONCLUSION: In neonates, infarcted brain tissue can be detected
      using DWI with high sensitivity during the first 2 days after stroke and before
      other sequences are diagnostic. However, the diffusion restriction does not
      persist beyond 1 week. After 5 days, diagnosis has to rest mainly on T2-weighted
      images.

PMID- 15490192
TI  - Sinus pericranii: from gross and neuroimaging findings to different
      pathophysiological changes.
AB  - CASE REPORTS: We report two girls with a typical presentation of sinus
      pericranii. Both patients received total excision of the subgaleal masses with
      complete obliteration of the communications to the intracranial portion. However,
      different gross appearances, neuroimaging findings and intraoperative findings
      were found. It took more time and attention to control the bleeding due to the
      large communication between the extracranial and intracranial components in the
      second case. DISCUSSION: Sinus pericranii is composed of abnormal extracranial
      vascular tissues that communicate directly with intracranial dural sinuses or
      veins. A review of the literature showed that 13 out of 31 patients with sinus
      pericranii had a high-flow pattern. Detailed physical examination and imaging
      studies to detect dilated scalp veins and a large bony defect should remind
      surgeons of the presence of large venous communications. Meticulous treatment of
      the large communication during surgery can avoid massive bleeding.

PMID- 15490193
TI  - Informed consent and choice in cholecystectomy.
AB  - As patients and parents seek more information and the threat of litigation
      increases, the process of informed consent has assumed greater importance. Data
      from large adult experiences indicate that the risk of bile duct injury, although
      small, is greater with laparoscopic cholecystectomy (LC) than open
      cholecystectomy. This complication has not yet been documented in pediatric
      practice, where cholecystectomy is relatively uncommon. What method do parents
      and patients choose if consent is truly informed? Of 57 consecutive children
      undergoing cholecystectomy, an open procedure was specifically indicated in 20
      (previous major gastrointestinal surgery in 11, concomitant major abdominal
      operation in four, and complex biliary tract disease in five) and LC in two
      (cystic fibrosis, severe autism). The remaining 35 patients were counseled in a
      standard manner about the relative merits of LC versus mini-cholecystectomy (MC)
      and allowed to choose. Specifically, they were informed that LC offers better
      cosmesis, less postoperative discomfort, and a shorter hospital stay, but in
      adults is associated with a slightly increased rate of bile duct injury (0.3-0.5%
      vs. 0.2%). All MCs were performed through a 4-cm incision. Parents chose LC in 23
      cases and MC in 12. The median age of both groups was similar. No surgical
      complications occurred, and there were no conversions in the LC group. No patient
      had retained stones. LC patients were discharged home after a mean of 1.7 days
      and MC patients after 2.3 days (0.1 > p > 0.05). If an open or laparoscopic
      technique is not specifically indicated and if parents/patients are fully
      informed, a significant minority may opt for mini-cholecystectomy.

PMID- 15490194
TI  - Mortality due to constipation and short-segment Hirschsprung's disease.
AB  - We report a case of mortality secondary to constipation. A 12-year-old child with
      a history of constipation from the age of 9 years presented in moribund condition
      with intestinal obstruction secondary to idiopathic constipation. He underwent
      laparotomy and died within 24 h of operation. At postmortem there was no evidence
      of abnormalities of the enteric nervous system. A 2nd case of early neonatal
      death from Hirschsprung's disease is presented to demonstrate that short-segment
      aganglionosis can be detected at postmortem. Enterocolitis can rapidly progress
      and be fatal in short-segment Hirschsprung's disease.

PMID- 15490195
TI  - A case of colorectal carcinoma in adenoma analyzed by a cDNA array.
AB  - PATIENT AND METHODS: A 68-year-old woman presenting with bloody stools and anemia
      was referred to our hospital. Colonoscopy showed a Is-type tumor of 45 mm in
      diameter in the cecum and three Is-type tumors in the ascending colon. Ileocecal
      resection with regional lymph node dissection was performed. Microscopically, the
      large tumor consisted of a well-differentiated adenocarcinoma with a
      tubulovillous adenoma (TVA) component (carcinoma in adenoma). Some carcinoma (CA)
      cells had invaded the submucosal layer, but the lymph nodes were negative for
      malignancy. The other three polyps were diagnosed as TVAs. Because her family
      history fulfilled the Amsterdam criteria II for hereditary non-polyposis
      colorectal cancer (HNPCC), genetic analysis was performed. All of the four tumor
      tissues were classified as microsatellite stable (MSS) according to the National
      Cancer Institute guideline for analysis of microsatellite instability (MSI). K
      ras mutation was detected in both CA and TVA lesions of the carcinoma in adenoma.
      To clarify relevant alterations of gene expression associated with adenoma
      carcinoma progression, the gene expression profiles of these tumor tissues were
      analyzed by a cDNA array. RESULTS: Although the gene expression profiles were
      similar, insulin-like growth factor-II (IGF-II) was expressed most differentially
      in CA and TVA tissues. The results were further substantiated by comparison of
      the gene expression profiles of CA and TVA lesions of the carcinoma in adenoma.
      CONCLUSION: The results suggest that overexpression of IGF-II played an important
      role in the progression of adenoma to carcinoma in this patient.

PMID- 15490197
TI  - Surgical management of combined rectal and genital prolapse in young patients:
      transabdominal approach.
AB  - BACKGROUND: The aim of this study was to determine the anatomical and functional
      outcomes of the simultaneous treatment of combined rectal and genital prolapse in
      young patients. METHODS: Between March 2001 and June 2002, eight female patients
      with symptomatic rectal and genital prolapse were enrolled in this study. The
      median age at the time of presentation was 44 years (range 34-53). All patients
      underwent simultaneous transabdominal treatment of their combined prolapse.
      Genital prolapse was treated by colpohysteropexy. Rectal prolapse was treated by
      mesh rectopexy or sutured rectopexy associated with sigmoid resection. The end
      evaluation to assess long-term results was performed after a median duration of
      follow-up of 17 months (range 10-24). Patients were asked about current problems
      with constipation, use of laxatives, incontinence and recurrence. RESULTS: The
      postoperative course was uneventful in 7 out of 8 cases. None of the patients had
      recurrence. Three patients out of 6 remained constipated postoperatively. One
      patient had a new onset of constipation postoperatively. None of the patients
      became faecally incontinent. Seven patients (87%) stated that they had improved
      overall after surgery. CONCLUSION: Combined rectal and genital prolapse in young
      women can be safely treated simultaneously using an abdominal approach. The
      genital prolapse should be treated by colpohysteropexy. The rectal prolapse
      should be treated by mesh rectopexy in patients who are not constipated, and by
      sutured rectopexy plus sigmoid resection in patients who are constipated
      preoperatively.

PMID- 15490199
TI  - Diet composition and age determine the effects of inulin-type fructans on
      intestinal calcium absorption in rat.
AB  - BACKGROUND: Although several studies in animals and humans have established that
      inulintype fructans (inulin, oligofructose, fructooligosaccharides) enhance
      intestinal Ca absorption, there are also reports that failed to demonstrate any
      effects of added fructans on Ca absorption. AIM OF THE STUDY: We investigated in
      a rat model what variables determine inulin actions on mineral absorption with
      special focus on the basic diet. METHODS: To determine apparent intestinal
      mineral absorption, whole body retention and mineral accumulation in bone, we
      performed feeding experiments with a balance technique by which mineral intake,
      faecal and urinary output are determined. RESULTS: In a first study we compared
      the effects of an inulin oligofructose mixture (0 and 10%,respectively) when
      added either to a standard diet or a semi-synthetic diet. Rats fed the semi
      synthetic diet were younger (adolescent) than rats on standard diet (young
      adult). We observed that the apparent Ca absorption ratio was significantly
      increased by inulin and oligofructose only when provided in the semisynthetic
      diet and not in the standard diet that intrinsically already contained some
      fructans from wheat. In our second study with a semi-synthetic diet fed to
      growing (adolescent) rats, inulin and oligofructose increased not only Ca but
      also Mg and Zn absorption, whole body mineral retention and femur mineral
      content. CONCLUSION: Inulin-type fructans at dietary levels of 10 % (w/w) do
      increase mineral absorption, retention and accumulation in bone in the case of
      Ca, Mg and Zn, but only when the basic diet for the control group contains no
      intrinsic fructans and when the mineral demand is particularly high as during
      growth.

PMID- 15490200
TI  - Lack of oxidative stress in a selenium deficient area in Ivory Coast--potential
      nutritional antioxidant role of crude palm oil.
AB  - BACKGROUND: Previous studies have described an important selenium deficiency in a
      mountain region (Glanle) in the west of Ivory Coast. AIM OF THE STUDY: To assess
      the antioxidant capacity of subjects from a selenium deficient area in Ivory
      Coast (Glanle region). METHODS: This study involved 57 subjects, 18 to 69 years
      old, living in the Glanle region and 56 healthy controls living in the southern
      coastal region (Bodou). In the Glanle region families consume basically a
      vegetarian and crude palm oil diet, whereas in the Bodou region, families eat a
      fish-based diet with principally refined palm oil. Fasting blood samples were
      collected to assess the following parameters: lipid status (plasma total lipids;
      total-, HDL and LDL-cholesterol; triglycerides; phospholipids; fatty acid
      composition), plasma protein status (total protein, albumin, transthyretin,
      orosomucoid, CRP, transferrin), antioxidant capacity (plasma selenium, uric acid,
      retinol, alpha-tocopherol and tocotrienols levels, plasma seleno-glutathione
      peroxidase (GSHPx) activity) and oxidative stress markers (malondialdehyde (MDA)
      and advanced oxidation protein products (AOPP)). RESULTS: The mountain region
      samples (Glanle) were characterized by significantly lower plasma albumin, total
      , HDL- and LDL-cholesterol, retinol and selenium levels, plasma PUFA content and
      GSHPx activity, but significantly higher alpha-tocopherol index and total
      tocotrienol level, than controls from the coastal area (Bodou). These results
      suggest a higher exposure risk to oxidative stress for the mountain region
      subjects. However, the absence of oxidative damage in this group provides
      evidence of a selenium independent protection mechanism against oxidative stress.
      This protection is related to lower plasma LDL cholesterol and PUFA content, and
      to higher alpha-tocopherol index, delta and total tocotrienols. CONCLUSION: The
      long-term consumption of crude palm oil could be considered as an effective
      protective factor against oxidative stress.

PMID- 15490201
TI  - Are QT measurements on body surface ECG indicative of ventricular refractory
      patterns?
AB  - OBJECTIVE: Increased dispersion (DISP) of refractoriness (ERP) facilitates the
      induction of malignant ventricular arrhythmias. Accordingly, QT DISP on surface
      ECG, supposedly reflecting ERP DISP, has been proposed as a noninvasive marker
      for risk stratification. However, a comparative analysis of local ERPs and QT
      measurements is not available so far. METHODS AND RESULTS: In 19 healthy dogs,
      standard 12 lead surface ECGs were recorded to measure QT and RR intervals. Based
      on these measurements, corrected QT intervals (QTc, Bazett formula) and DISP
      (maximum difference) of both QT and QTc intervals (QT-DISP and QTc-DISP,
      respectively) were calculated. Subsequently, 60 custom-made needle electrodes (12
      mm long, 4 bipolar electrodes per needle, interelectrode distance 2.5 mm) were
      inserted into the left (LV) and right ventricle (RV). At each bipole of 14
      randomly selected needle electrodes (8 LV, 6 RV) local ERPs were determined
      (extrastimulus technique, basic cycle length 1000 ms). Interventricular DISP of
      ERP (LV-RV-DISP) was defined as the difference between the longest and shortest
      ERP within both ventricles. Respective values were calculated for each ventricle
      (LV-DISP; RV-DISP). Scatter plots and correlation analysis did not reveal a
      significant correlation between QT, QTc, QT-DISP, QTc-DISP and any of the ERP
      measurements or calculations. Although not statistically significant, the closest
      correlation was found between QTc and mean ERP and between QTc-DISP and LV-RV
      DISP. CONCLUSION: QT measurements on surface ECG are poorly correlated with local
      ERPs. If anything, QT- or QTc-DISP might provide a rough estimate of
      interventricular, that is, global DISP of ERP. Local or even intraventricular
      DISP of ERP is definitely not reflected by these QT measurements.

PMID- 15490202
TI  - The angiotensin II type 1 receptor blocker valsartan attenuates graft
      vasculopathy.
AB  - OBJECTIVE: Transplant arteriosclerosis remains the major cause of graft failure
      after cardiac transplantation. Here, we investigated the effects of the
      angiotensin II type 1 receptor blocker valsartan on the development of transplant
      arteriosclerosis in a murine model of cardiac transplantation. METHODS: Hearts
      from DBA/2 (H-2(d)) mice were heterotopically transplanted into B10.D2 (H-2(d))
      mice. Recipients were treated with oral administration of valsartan (10
      mg/kg/day) or vehicle. RESULTS: Morphometrical analysis of the cardiac allografts
      harvested at 30 days revealed that valsartan significantly reduced the
      development of coronary atherosclerosis (intima/media ratio: 0.39 +/- 0.05 vs.
      0.66 +/- 0.08, P < 0.01). At two weeks after transplantation, there was no
      significant difference between the two groups in expression of adhesion molecules
      and cytokines. Valsartan significantly reduced the number of peripheral
      mononuclear cells that differentiated into smooth muscle-like cells in the
      presence of basic fibroblast growth factor and platelet-derived growth factor BB
      (18.0 +/- 1.5 vs. 30.3 +/- 4.4 cells/HPF, P = 0.01). CONCLUSIONS: These results
      suggest that angiotensin II plays a role in the pathogenesis of transplant
      arteriosclerosis and that blockade of angiotensin II type 1 receptor might be
      effective as a prophylactic therapy for transplant arteriosclerosis along with
      conventional immunosuppressive drugs.

PMID- 15490203
TI  - Ablation of Ca(v)2.3 / E-type voltage-gated calcium channel results in cardiac
      arrhythmia and altered autonomic control within the murine cardiovascular system.
AB  - Voltage-gated calcium channels are key components in cardiac electrophysiology.
      We demonstrate that Ca(v)2.3 is expressed in mouse and human heart and that mice
      lacking the Ca(v)2.3 voltage-gated calcium channel exhibit severe alterations in
      cardiac function. Amplified cDNA fragments from murine heart and single
      cardiomyocytes reveal the expression of three different Ca(v)2.3 splice variants.
      The ablation of Ca(v)2.3 was found to be accompanied by a compensatory
      upregulation of the Ca(v)3.1 T-type calcium channel, while other voltage-gated
      calcium channels remained unaffected. Telemetric ECG recordings from Ca(v)2.3
      deficient mice displayed subsidiary escape rhythm, altered atrial activation
      patterns, atrioventricular conduction disturbances and alteration in QRS
      morphology. Furthermore, time domain analysis of heart rate variability (HRV) in
      Ca(v)2.3(-/-) mice exhibited a significant increase in heart rate as well as in
      the coefficient of variance (CV) compared to control mice. Administration of
      atropin/propranolol revealed that increased heart rate was due to enhanced
      sympathetic tonus and that partial decrease of CV in Ca(v)2.3(-/-) mice after
      autonomic block was in accordance with a complete abolishment of 2(nd) degree
      atrioventricular block. However, escape rhythms, atrial activation disturbances
      and QRS-dysmorphology remained unaffected, indicating that these are intrinsic
      cardiac features in Ca(v)2.3(-/-) mice. We conclude that the expression of
      Ca(v)2.3 is essential for normal impulse generation and conduction in murine
      heart.

PMID- 15490204
TI  - Diastolic left ventricular function Experimental study of the early filling
      period using the Voigt model.
AB  - BACKGROUND: The left ventricular (LV) diastolic function is usually described by
      the diastolic part of the LV pressure-volume relationship (PVR). The mathematical
      analysis of the PVR provides parameters of diastolic LV as well as myocardial
      function. Up to now, all approaches assume the myocardium as a passive elastic
      medium. This implies that each increase in LV volume is associated with a
      corresponding increase in LV pressure. Obviously this does not agree with actual
      PVR's during the LV early filling phase, where a decrease of pressure (due to
      relaxation) can be observed. Therefore, we analysed the LV diastolic PVR using
      the Voigt model to provide a better understanding of the concomitant processes of
      relaxation and filling especially during the early diastole. METHODS AND RESULTS:
      LV volumes and pressures were measured in an experimental study (6 pigs) using
      biplane cineangiography (100 frames/s) and simultaneous pressure measurements
      (catheter tip manometer). LV volumes were determined from all cine frames of
      total cardiac cycles. Instantaneous (beat to beat) changes in duration
      (Deltat(f)) of the LV filling period were achieved by atrial stimulation and by
      releasing post-extrasystolic beats. A total of 26 PVR's with different Deltat(f)
      were evaluated. According to the Voigt model the compliance (product of the
      resting volume V(0) and the elastic coefficients) of the total muscle fibre
      (V(0).K(tot)) and of the serial elastic element (V(0).K(se)) were calculated
      (average: V(0).K(tot) = 3.43 ml/ mmHg; V(0).K(se) = 5.07 ml/mmHg; n = 26). The
      interindividual differences between the compliances were in some individuals
      significant (V(0).K(tot): p < 5% in 6 of 15 Wilcoxon tests ; V(0).K(se): p < 5%
      in 3 of 15 Wilcoxon tests) but the intraindividual range of these parameters (due
      to different Deltat(f)) were in some cases as pronounced as the interindividual
      differences. CONCLUSIONS: As in 22 of 26 measurements V(0).K(tot) is less than
      V(0).K(se) it must be concluded that the early diastolic PVR cannot be described
      by passive elasticity and the laws of elastomechanics only. These inconsistencies
      can be explained by the early diastolic LV suction (untwisting) as well as by
      recent findings regarding the titin filament. Both mechanisms augment LV
      diastolic filling even in unfavourable working conditions (shortened filling)
      such as exercise.

PMID- 15490209
TI  - High-resolution magic angle spinning 1H NMR spectroscopy of metabolic changes in
      rabbit lens after treatment with dexamethasone combined with UVB exposure.
AB  - BACKGROUND: Long-term steroid treatment and UVB exposure are well-known
      cataractogenic factors. The purpose of this study was to investigate metabolic
      changes in the rabbit lens after long-term dexamethasone treatment in combination
      with UVB exposure, using high-resolution magic angle spinning proton nuclear
      magnetic resonance (HR-MAS (1)H NMR) spectroscopy to analyse intact lens tissues.
      METHODS: Rabbits received topical doses of 0.1% dexamethasone or 0.9% saline (50
      microl) four times daily for 36 days. On day 37, the eyes were exposed to UVB
      radiation (2.05 J/cm(2)). Twenty-four hours later the animals were killed, and HR
      MAS (1)H NMR spectra of lens tissues were obtained. RESULTS: More than 15 major
      metabolites were assigned in NMR spectra of rabbit lenses. The combined treatment
      with dexamethasone and UVB induced large reductions in the concentration of
      reduced glutathione, inositols, taurine and lactate compared with normal lenses.
      Concurrently, the levels of glucose, sorbitol and sorbitol-3-phosphate were
      increased. After exposure to UVB radiation only, the most significant finding was
      a decrease in the concentration of lactate. No lens opacities were detected.
      CONCLUSIONS: HR-MAS (1)H NMR spectroscopy was found to be an efficient tool for
      analysis of intact lens tissues. High-resolution NMR spectra of intact lens
      tissue enabled metabolic changes to be quantified. Long-term treatment with
      dexamethasone combined with UVB exposure induced substantial metabolic changes,
      dominated by osmolytic regulation processes and loss of glutathione.

PMID- 15490217
TI  - Optical coherence tomographic findings in pregnancy-associated central serous
      chorioretinopathy.
AB  - PURPOSE: To report the presence and disappearance of subretinal fibrinous exudate
      in pregnancy-induced central serous chorioretinopathy studied with optical
      coherence tomography (OCT). METHODS: Case report. A 32-year-old woman was
      referred for ophthalmoscopic evaluation in her 32nd week of pregnancy,
      complaining of reduced vision in her right eye. RESULTS: The funduscopic
      examination revealed a serous detachment of the macula with subretinal exudative
      deposits in the right eye and a peripapillary serous detachment in the left eye.
      OCT sections through the right macula demonstrated serous elevation of the retina
      and the presence of highly reflective material in the subretinal space. Two weeks
      after delivery, OCT showed resolution of subretinal fluid and the disappearance
      of submacular exudate in the right eye. CONCLUSION: During pregnancy and
      immediately after delivery, OCT may provide information reflecting the
      relationship between the retina, subretinal space, and retinal pigment epithelium
      without any known adverse effects to the infant. In a patient with pregnancy
      associated central serous chorioretinopathy, a highly reflective material,
      presumably fibrin, was detected spanning the subretinal space that was
      subsequently shown to disappear. This information may help us better understand
      the pathological retinal changes that may occur during pregnancy.

PMID- 15490218
TI  - Immunocytochemical distribution of somatotrophs in porcine anterior pituitary.
AB  - The objective of this immunohistochemical study was to identify the spatial
      distribution patterns of growth hormone (GH) secreting cells (somatotrophs) in
      the newborn and prepubertal porcine pituitary. No differences were observed among
      the total somatotrophs per unit area across the three ages. There were, however,
      changes in spatial distribution of somatotrophs in porcine pituitary with
      developmental age. Distinctive characteristics of the pattern included a high
      population of somatotrophs (44 +/- 1.2; mean +/- standard error of the mean per
      30,495 microm(2)) in regions 1 and 5 and a low population (22 +/- 1.4) in regions
      2 and 4 at each level (P < 0.05). Somatotrophs increased 55% in region 3 from
      proximal to distal levels at all ages. With increasing age, however, somatotrophs
      in region 3 at the proximal level decreased 33%. From these results, we suggest
      that there may be regional specificity of cellular differentiation and
      transformation to facilitate GH secretion to meet the need for endocrine
      regulation as the animal ages.

PMID- 15490219
TI  - Intense training: mucosal immunity and incidence of respiratory infections.
AB  - This investigation examined the impact of a multistressor situation on salivary
      immunoglobulin A (sIgA) levels, and incidence of upper respiratory tract
      infection (URTI) during the French commando training (3 weeks of training
      followed by a 5-day combat course). For the URTI, the types of symptoms were
      classified according to the anatomical location of the infection. Saliva samples
      were collected (8 a.m.) from 21 males [21 (2) years] before entry into the
      commando training, the morning following the 3 weeks of training, after the 5-day
      combat course, and after 1 week of recovery. sIgA, protein and cortisol
      concentrations were measured. Symptoms of URTI were recorded during the study
      from health logs and medical examinations. After the 3 weeks of training, the
      sIgA concentration was not changed, although it was reduced after the 5-day
      course [from 120 (14) mg l(-1) to 71 (9) mg l(-1), P<0.01]. It returned to pre
      training levels within a week of recovery. The incidence of URTI increased during
      the trial (chi(2)=53.48; P<0.01), but was not related to sIgA. Among the 30
      episodes of URTI reported, there were 12 rhino-pharyngitis, 6 bronchitis, 5
      tonsillitis, 4 sinusitis and 3 otitis. Cortisol levels were raised after the 3
      week training (P<0.01), dropping below baseline after the combat course (P<0.01).
      Stressful situations have an adverse effect on mucosal immunity and incidence of
      URTI. However, the relationship between sIgA and illness remained unclear. The
      large proportion of rhino-pharyngitis indicated that the nasopharyngeal cavity is
      at a higher risk of infection.

PMID- 15490220
TI  - Neural activation of the triceps surae is impaired following 2 weeks of
      immobilization.
AB  - The purpose of this study was to investigate the effect of 2 weeks of ankle joint
      immobilization on triceps surae neural activation, with particular emphasis on
      the potential differences between the monoarticular soleus and the biarticular
      gastrocnemius muscles. Seventeen male volunteers were divided into the
      immobilized group (IG, n = 8) and the control group (CG, n = 9). Elastic adhesive
      bandages and an ankle stabilization orthosis were used to immobilize the ankle
      joint only. The plantar flexor torque obtained during maximal voluntary
      contractions (MVC) and after single, paired and tetanic stimuli applied at rest
      was measured. The associated EMG activity from the soleus and gastrocnemius
      muscles was also recorded, and their activation levels were estimated by means of
      the twitch interpolation technique. After immobilization, triceps surae maximal
      voluntary torque significantly decreased by 17% (P < 0.001). Strength losses were
      accompanied by a decrement in activation level (-6%, average of the three
      techniques used) and in maximal 100 Hz tetanic force (-11%). A significant
      decrease in the soleus (-22%, P < 0.05) but not in the gastrocnemius EMG
      activity, normalized to respective M-waves, was also found. It was concluded that
      the reduced voluntary torque output after immobilization could be attributed to
      both muscular and neural alterations. These latter selectively involved the
      monoarticular soleus muscle, while neural drive to the biarticular gastrocnemii,
      which had not been immobilized in their function as knee flexors, was preserved.

PMID- 15490221
TI  - Absence of long-term modulation of ventilation by dead-space loading during
      moderate exercise in humans.
AB  - The stability of arterial PCO(2) (P(a)CO(2)) during moderate exercise in humans
      suggests a CO(2)-linked control that matches ventilation (V(E)) to pulmonary
      CO(2) clearance (VCO(2)). An alternative view is that V(E) is subject to long
      term modulation (LTM) induced by "hyperpnoeic history". LTM has been reported
      with associative conditioning via dead-space (V(D)) loading in exercising goats
      (Martin and Mitchell 1993). Whether this prevails in humans is less clear, which
      may reflect differences in study design (e.g. subject familiarisation; V(D) load;
      whether or not V(E) is expressed relative to VCO(2); choice of P(a)CO(2)
      estimator). After familiarisation, nine healthy males performed moderate constant
      load cycle-ergometry (20 W-80 W-20 W; <lactate threshold, theta;(L)): day 1, pre
      conditioning, n=3; day 2, conditioning (V(D)=1.59 l, doubling V(E) at 20 W and 80
      W), n=8 with 10 min rest between tests; and, after 1 h rest, post-conditioning,
      n=3. Gas exchange was determined breath-by-breath. Post-conditioning, neither the
      transient [phase 1, phase 2 (capital EF, Cyrillic1, capital EF, Cyrillic2)] nor
      steady-state V(E) exercise responses, nor their proportionality to VCO(2),
      differed from pre-conditioning. For post-conditioning trial 1, steady-state V(E)
      was 28.1 (4.7) l min(-1) versus 29.1 (3.8) l min(-1) pre-conditioning, and mean
      alveolar PCO(2) (a validated P(a)CO(2) estimator) was 5.53 (0.48) kPa [41.5 (3.6)
      mmHg] versus 5.59 (0.49) kPa [41.9 (3.7) mmHg]; the capital EF, Cyrillic1 V(E)
      increment was 4.2 (2.9) l min(-1) versus 5.2 (1.9) l min(-1); the capital EF,
      Cyrillic2 V(E) time-constant (tau) was 64.4 (24.1) s versus 64.1 (25.3) s;
      tauV(E)/tauVCO(2) was 1.12 (0.04) versus 1.10 (0.04); and the V(E)-VCO(2) slope
      was 21.7 (3.4) versus 21.2 (3.2). In conclusion, we could find no evidence to
      support ventilatory control during moderate exercise being influenced by
      hyperpnoeic history associated with dead-space loading in humans.

PMID- 15490222
TI  - Effects of exercise training and detraining on cutaneous microvascular function
      in man: the regulatory role of endothelium-dependent dilation in skin
      vasculature.
AB  - This study investigated how exercise training and detraining affect the cutaneous
      microvascular function and the regulatory role of endothelium-dependent dilation
      in skin vasculature. Ten healthy sedentary subjects cycled on an ergometer at 50%
      of maximal oxygen uptake (VO(2max)) for 30 min daily, 5 days a week, for 8 weeks,
      and then detrained for 8 weeks. Plasma nitric oxide (NO) metabolites (nitrite
      plus nitrate) were measured by a microplate fluorometer. The cutaneous
      microvascular perfusion responses to six graded levels of iontophoretically
      applied 1% acetylcholine (ACh) and 1% sodium nitroprusside (SNP) in the forearm
      skin were determined by laser Doppler. After training, (1) resting heart rate and
      blood pressure were reduced, whereas VO(2max), skin blood flow and cutaneous
      vascular conductance to acute exercise were enhanced; (2) plasma NO metabolite
      levels and ACh-induced cutaneous perfusion were increased; (3) skin vascular
      responses to SNP did not change significantly. However, detraining reversed these
      effects on cutaneous microvascular function and plasma NO metabolite levels. The
      results suggest that endothelium-dependent dilation in skin vasculature is
      enhanced by moderate exercise training and reversed to the pretraining state with
      detraining.

PMID- 15490223
TI  - Nondirectional motion may underlie insect behavioral dependence on image speed.
AB  - Behavioral experiments suggest that insects make use of the apparent image speed
      on their compound eyes to navigate through obstacles, control flight speed, land
      smoothly, and measure the distance they have flown. However, the vast majority of
      electrophysiological recordings from motion-sensitive insect neurons show
      responses which are tuned in spatial and temporal frequency and are thus unable
      to unambiguously represent image speed. We suggest that this contradiction may be
      resolved at an early stage of visual motion processing using nondirectional
      motion sensors that respond proportionally to image speed until their peak
      response. We describe and characterize a computational model of these sensors and
      propose a model by which a spatial collation of such sensors could be used to
      generate speed-dependent behavior.

PMID- 15490224
TI  - Neural network model of selective visual attention using Hodgkin-Huxley equation.
AB  - We propose a mathematical model of selective visual attention using a two-layered
      neural network with neurons described by the Hodgkin-Huxley equation in order to
      investigate part of the assumption proposed by Desimone and Duncan. The neural
      network consists of a layer of hippocampal formation and of visual cortex. A
      frequency of firing and a firing time for each neuron and also a correlation of
      the firing times between neurons are calculated numerically to clarify an
      attention state, a nonattention state, and an attention shift. We find that
      synchronous phenomena occur not only for the frequency but also for the firing
      time between the neurons in the hippocampal formation and those in a part of the
      visual cortex in our model. It also turns out that the attention shift is
      performed quickly in our model.

PMID- 15490226
TI  - In vivo heat shock preconditioning mitigates calcium overload during
      ischaemia/reperfusion in the isolated, perfused rat heart.
AB  - Heat shock (HS) pretreatment of the heart is effective in mitigating the
      deleterious effects of ischaemia/reperfusion. The main objective of this study
      was to determine whether the beneficial effect of HS is associated with the
      preservation of intracellular Ca2+ handling in the ischaemic/reperfused, isolated
      rat heart. Twenty-four hours after raising body core temperature to 42 degrees C
      for 15 min, rat hearts were perfused according to Langendorff and subjected to 30
      min ischaemia followed by 20 min reperfusion. Cyclic changes of cytoplasmic
      calcium ion [Ca2+i] levels were measured by surface fluorometry using Indo-1 AM.
      Reperfused HS hearts showed improved recovery of contractile function compared
      with control hearts: end-diastolic pressure: 45+/-11 vs. 64+/-22 mmHg; developed
      pressure: 72+/-12 vs. 41+/-20 mmHg; maximum rate of pressure increase
      (+dP/dtmax): 1,513+/-305 vs. 938+/-500 mmHg/s; maximum rate of pressure decrease
      (-dP/dtmax): -1,354+/-304 vs. -806+/-403 mmHg/s. HS hearts displayed a
      significantly lower end-diastolic cytosolic [Ca2+] ([Ca2+]i) after reinstallation
      of flow. The dynamic parameters of the Ca2+i transients, i.e. the maximum rate of
      increase/decrease (+/-dCa2+i/dtmax) and amplitude, did not differ between
      reperfused control and HS hearts. The novel finding of this study is that
      improved performance of the HS-preconditioned heart after an ischaemic insult is
      associated with a reduced end-diastolic Ca2+i load, and most likely, preserved
      Ca2+ sensitivity of the myocardial contractile machinery.

PMID- 15490227
TI  - Effects of vanadate, phosphate and 2,3-butanedione monoxime (BDM) on skinned
      molluscan catch muscle.
AB  - The effects of orthovanadate (V(i)), inorganic phosphate (P(i)) and 2,3
      butanedione monoxime (BDM) on tension, force transients and the catch state
      (passive tension maintenance) were investigated in saponin-skinned fibre bundles
      of the anterior byssus retractor muscle (ABRM) of the bivalve mollusc Mytilus
      edulis at pH 6.7. During maximal Ca(2+) activation isometric force was depressed
      by V(i) (0.03-10 mM), P(i) (10 mM) and BDM (50 mM). Force transients following
      quick stretches (0.1-0.3% of fibre length) were accelerated substantially by 1 mM
      V(i), 10 mM P(i) or 50 mM BDM. These compounds also accelerated force responses
      in experiments in which ATP was released rapidly from caged ATP by flash
      photolysis at both pCa 4.7 (force rise) and at pCa>8 (force decline). The effects
      on the catch state were investigated in two types of experiments: (1) Ca(2+)
      removal after maximal Ca(2+) activation and (2) rapid ATP release during high
      force rigor at pCa>8. In both cases rapid relaxation was followed by slow
      relaxation (slower than 2% of initial force per min). This later slow relaxation
      (catch) was insensitive to V(i) (1-10 mM), P(i) (10 mM) and BDM (50 mM) but was
      accelerated by 0.12 mM cAMP. Complete relaxation to almost zero force was
      attained by changing pH from 6.7 to 7.7 (pCa>8). We conclude that catch depends
      on cAMP- and pH-sensitive structures linking the myofilaments and not on the
      force-generating actomyosin cross-bridges that are sensitive to V(i), P(i) and
      BDM.

PMID- 15490228
TI  - An agglutinating chitinase with two chitin-binding domains confers fungal
      protection in transgenic potato.
AB  - Brassica juncea BjCHI1 is a unique chitinase with two chitin-binding domains.
      Here, we show that, unlike other chitinases, potato-expressed BjCHI1 shows
      hemagglutination ability. BjCHI1 expression in B. juncea seedlings is induced by
      Rhizoctonia solani infection, suggesting its protective role against this fungus.
      To verify this, transgenic potato (Solanum tuberosum L. cv. Desiree) plants
      expressing BjCHI1 generated by Agrobacterium-mediated transformation were
      challenged with R. solani. We also transformed potato with a cDNA encoding Hevea
      brasiliensis beta-1,3-glucanase, designated HbGLU, and a pBI121-derivative that
      contains cDNAs encoding both BjCHI1 and HbGLU. In vitro fungal bioassays using
      Trichoderma viride showed that extracts from transgenic potato lines co
      expressing BjCHI1 and HbGLU inhibited fungal growth better than extracts from
      transgenic potato expressing either BjCHI1 or HbGLU, suggesting a synergistic
      effect. Consistently, in vivo fungal bioassays with soil-borne R. solani on young
      transgenic potato plants indicated that the co-expressing plants showed healthier
      root development than untransformed plants or those that expressed either BjCHI1
      or HbGLU. Light microscopy and transmission electron microscopy revealed abundant
      intact R. solani hyphae and monilioid cells in untransformed roots and
      disintegrated fungus in the BjCHI1-expressing and the BjCHI1 and HbGLU co
      expressing plants. Observations of collapsed epidermal cells in the co-expressing
      potato roots suggest that these proteins effectively degrade the fungal cell
      wall, producing elicitors that initiate other defense responses causing epidermal
      cell collapse that ultimately restricts further fungal penetration.

PMID- 15490230
TI  - Spatio-temporal expression of a DAZ-like gene in the Japanese newt Cynops
      pyrrhogaster that has no germ plasm.
AB  - To investigate the germ cell specification in urodeles, we cloned a DAZ-like
      sequence from the Japanese newt Cynops pyrrhogaster, Cydazl, and raised
      antibodies specific to Cydazl. Cydazl is a homologue of the human DAZ (deleted in
      azoospermia), DAZL, and Xenopus dazl genes, which are involved in gametogenesis
      or germ cell specification. During gametogenesis, expression of Cydazl mRNA and
      Cydazl protein was detected at first in the small previtellogenic oocytes in
      females but was not localized as seen in Xenopus and was restricted to secondary
      spermatogonia prior to meiosis in males. During early embryogenesis, maternal
      stores of the Cydazl transcript and protein were present in the entire embryos,
      not localized in any specific region. The zygotic expression was detected in
      hatching larvae (stage 50) by RT-PCR analysis whereas specific cells expressing
      Cydazl could not be determined by in situ hybridization at this stage. Strong
      expression of Cydazl and Cydazl were detected in primordial germ cells (PGCs)
      that had entered the gonadal rudiment at late stage 59. These results suggest
      that Cydazl does not function early in development, for the specification of germ
      cells, but functions later for differentiation of germ cells in the developing
      gonads during embryogenesis and for meiotic regulation, supporting the previous
      idea of an intermediate germ cell formation mode in urodeles.

PMID- 15490231
TI  - Organization of the Hox gene cluster of the silkworm, Bombyx mori: a split of the
      Hox cluster in a non-Drosophila insect.
AB  - A bacterial artificial chromosome (BAC) contig was constructed by chromosome
      walking, starting from the Hox genes of the silkworm, Bombyx mori. Bombyx
      orthologues of the labial (lab) and zerknult (zen) genes were newly identified.
      The size of the BAC contig containing the Hox gene cluster-except the lab and Hox
      2 genes-was estimated to be more than 2 Mb. The Bombyx Hox cluster was mapped to
      linkage group (LG) 6. The lab gene was mapped on the same LG, but far apart from
      the cluster. Fluorescence in situ hybridization analysis confirmed that the major
      Hox gene cluster and lab were at different locations on the same chromosome in B.
      mori.

PMID- 15490233
TI  - Extensive necrotising fasciitis caused by Pseudomonas aeruginosa in a child with
      acute myeloid leukaemia: case report and literature review.

PMID- 15490234
TI  - Alterations in gene expression associated with the overexpression of a splice
      variant of DNA methyltransferase 3b, DNMT3b4, during human hepatocarcinogenesis.
AB  - PURPOSE: Overexpression of a splice variant of DNA methyltransferase 3b, DNMT3b4,
      correlates significantly with DNA hypomethylation in pericentromeric satellite
      regions, which is known to result in centromeric decondensation and enhanced
      chromosomal recombination in precancerous conditions and hepatocellular
      carcinomas (HCCs). We aimed to elucidate further the significance of DNMT3b4
      during human hepatocarcinogenesis. METHODS: DNMT3b4-transfected human epithelial
      293 cells were characterized using growth rate measurements, gene expression
      microarray, and quantitative reverse transcription-polymerase chain reaction (RT
      PCR) analyses. RT-PCR was also performed on eight normal liver specimens, 45
      noncancerous liver specimens showing chronic hepatitis or cirrhosis, which are
      considered to be precancerous conditions, and 56 HCCs. RESULTS: The growth rate
      of the DNMT3b4 transfectants was about double that of mock-transfectants.
      Induction of signal transducer and activator of transcription 1 (STAT1), an
      effector of interferon signaling, and of a set of downstream genes implicated in
      such signaling, was observed in the DNMT3b4 transfectants. There was significant
      correlation between the mRNA expression levels of DNMT3b4 and STAT1 in HCCs. mRNA
      expression levels of STAT1 and the three downstream genes examined were all
      significantly elevated in the chronic hepatitis and cirrhosis specimens compared
      with the normal liver specimens. Among the HCCs, the mRNA expression levels of
      STAT1 and the downstream genes were higher in tumors without portal vein
      involvement than in more malignant HCCs with portal vein involvement. Significant
      correlations between the mRNA expression levels of STAT1 and each of the
      downstream genes were observed in the tissue samples. CONCLUSIONS: Overexpression
      of DNMT3b4 is involved in human hepatocarcinogenesis, even at the precancerous
      stages, not only by inducing chromosomal instability but also by affecting the
      expression of specific genes.

PMID- 15490235
TI  - A hybrid protein of the amino-terminal fragment of urokinase and mutant
      plasminogen activator inhibitor-2 efficiently inhibits tumor cell invasion and
      metastasis.
AB  - The urokinase plasminogen activator(uPA) system plays important roles in tumor
      cell invasion and metastasis. In the present study, we evaluated the effects of
      ATF-PAI2CD, a hybrid protein of the amino-terminal fragment of urokinase and
      mutant plasminogen activator inhibitor-2, on 95D cells in vitro and in vivo.
      Furthermore, our results support a current hypothesis that fusion protein blocks
      tumor invasion and motility by inhibiting localized pericellular proteolysis.
      Treatment of 95D cells with ATF-PAI2CD resulted in a dose-dependent decrease in
      tumor-cell invasion through matrigel, and ATF-PAI2CD was much more effective than
      PAI-2CD. In addition, extracellular regular protein kinase (ERK1/2) expression
      was downregulated and the adhesion ability to fibronectin was increased in 95D
      cells treated with the fusion protein, which was confirmed by cell adhesion
      assay. A high-concentration of ATF-PAI2CD caused a significant reduction in tumor
      volume and weight in BALB/c (nu/nu) mice female inoculated with human 95D cells
      (5 x 10(6)); the antitumor effects were significant, which demonstrated a 67.9+/
      4.2% reduction in tumor growth compared with control mice. The number of
      lymphatic metastasis was significantly reduced in mice treated with high- and
      middle- concentrations of ATF-PAI2CD, whereas a low-concentration of ATF-PAI2CD
      failed to exhibit any antimetastatic effects. In conclusion, the results
      suggested that the hybrid protein has therapeutic potential for lung carcinoma
      and other tumors to inhibit tumor invasion and metastasis.

PMID- 15490236
TI  - Enhanced expression of transforming growth factor-beta1 in inflammatory cells and
      secretory granules in Paneth cells in the small intestine of mice infected with
      Toxocara canis.
AB  - The small intestine is the initial organ which Toxocara canis larvae invade.
      Information on intestinal pathological changes associated with transforming
      growth factor-beta1 (TGF-beta1) and secretory granules (SG) in Paneth cells (PCs)
      caused by T. canis is unclear. Mice orally inoculated with 250 T. canis infective
      eggs were evaluated by pathological and immunohistochemical assessments with a
      294-day investigation. Pathologically, the inflammatory reactions with or without
      trapped larvae in the submucosa were observed only within the first 28 days post
      infection (DPI), with inflammatory injury ranging from severe during 2 DPI to
      mild between 7 and 28 DPI. The crypts of Leiberkuhn were major larval penetration
      sites. Enhanced expression of SG in PCs appeared earlier than those of TGF-beta1
      in infiltrating cells. The significance of both effectors might be related to the
      host's defense against larval invasion in the intestinal phase of toxocaral
      infection.

PMID- 15490237
TI  - Distribution of sandfly species in relation to canine leishmaniasis from the Ebro
      Valley to Valencia, northeastern Spain.
AB  - In Spain, only two of the 12 recorded species of sandflies, Phlebotomus
      (Larroussius) ariasi Tonnoir and P. (L.) perniciosus Newstead, are proven vectors
      of Leishmania infantum Nicolle, the causative agent of endemic leishmaniasis.
      Studies of the distributions of phlebotomine sandflies are important for
      evaluating the possible effects of climate warming on any northward or
      altitudinal range shifts of leishmaniasis or the other diseases they transmit. We
      describe a recent sandfly survey in Spain, starting in the northern Ebro Valley
      and continuing southeast into the Levante region of the Mediterranean coast.
      Sandflies (P. ariasi only) were found for the first time in the northern province
      of Alava, in the upper Ebro Valley, where cases of canine leishmaniasis have been
      described during the last decade. Throughout the provinces sampled, P. ariasi
      predominated over P. perniciosus in cooler bioclimatic zones, and this
      statistically significant pattern was more marked than that with higher
      altitudes.

PMID- 15490238
TI  - Molecular genetic characterization and subcellular localization of a putative
      Theileria annulata membrane protein.
AB  - A Theileria annulata protein (TaD) exhibiting an N-terminal signal sequence for
      endoplasmic reticulum membrane translocation and a conserved cysteine-rich region
      was isolated by screening the mRNA of a T. annulata-infected bovine
      lymphoblastoid cell line with degenerated primers directed against T. annulata
      targeting sequences. The TaD-coding sequence was found to be most closely related
      to the genomic DNA sequence of T. parva (TIGR database, 72%) and the amino acid
      sequence of Plasmodium falciparum (41%), P. yoelii yoelii (38%) and
      Cryptosporidium parvum (36%). The TaD mRNA is expressed within the sporozoite,
      schizont and merozoite stages of the parasite, implying that it is constitutively
      transcribed throughout the parasite's life cycle. Allelic variants were found
      between isolates originating from different geographical regions, however not
      affecting conserved cysteines. The open reading frame encoded a protein of 19.5
      kDa and non-reducing SDS-PAGE analysis demonstrated a homodimeric protein. Using
      confocal microscopy, the protein was found to be both located in the parasite
      cytoplasm and to colocalize with a transmembrane protein of the schizonts within
      infected cells.

PMID- 15490241
TI  - Adipose tissue in Walker 256 tumour-induced cachexia: possible association
      between decreased leptin concentration and mononuclear cell infiltration.
AB  - The adipose tissue (AT) is severely affected by cachexia, a paraneoplastic
      syndrome, which increases the morbidity and mortality of cancer. There is,
      however, a heterogeneous response to the condition, according to the AT depot. As
      plasma leptin concentration has been often reported to vary in cachexia, we have
      measured (species specific radioimmunoassay) the local concentration of leptin in
      three AT depots: retroperitoneal (RPAT), epididymal (EAT) and mesenteric (MES) of
      Walker 256 tumour-bearing rats. A reduced concentration of leptin ( P<0.0001) was
      found in all the depots and in the plasma of the cachectic rats, compared with
      controls already from day 4 after tumour cell injection. The presence of a cell
      infiltrate was observed in all AT obtained from the tumour-bearing animals.
      Ultrastructural analysis, along with immunocytochemistry for RT1B (indicating the
      presence of MHCII) and using antibody against mononuclear phagocytes, showed the
      cells to be macrophages. The profile of TNFalpha and PGE2 secretion by the
      infiltrate was investigated (commercial kits). There was increased production of
      both factors by the cells of all AT ( P<0.05) compared with peritoneal
      macrophages obtained from the cachectic rats, while the cells isolated from MES
      showed the highest synthesis of TNFalpha. The results suggest a possible
      modulation of the chronic locally produced TNFalpha and PGE2 upon leptin
      synthesis by the AT of the cachectic rats.

PMID- 15490240
TI  - The CLCA gene locus as a modulator of the gastrointestinal basic defect in cystic
      fibrosis.
AB  - To determine whether the CLCA gene family of calcium-activated chloride channels
      is a modulator of the basic defect of cystic fibrosis (CF), an association study
      was performed with polymorphic microsatellite markers covering a 40-Mbp region
      spanning the CLCA gene locus on human chromosome 1p in CF patients displaying CF
      transmembrane conductance regulator (CFTR)-independent residual chloride
      conductance in gastrointestinal epithelia. Statistically significant association
      of the electrophysiological phenotype with the allele distribution of markers 5'
      of and within the CLCA locus was observed. Transmission disequilibrium and the
      significance of the association decreased within the locus from hCLCA2 towards
      hCLCA4. Expression of hCLCA1 and hCLCA4 in human rectal mucosa was proven by
      microarray analysis. The CLCA gene region was identified to encode mediators of
      DIDS-sensitive anion conductance in the human gastrointestinal tract that
      modulate the CF basic defect.

PMID- 15490242
TI  - Normal but not altered mucins activate neutrophils.
AB  - Interactions between leucocytes and their surroundings are mediated through
      oligosaccharide epitopes, some of which are also expressed on ocular mucins.
      Neutrophils represent the majority of immune cells in the proinflammatory
      environment of the ocular surface during sleep. We have tested whether changes in
      mucin glycosylation, as occur in dry eyes, influence the phenotype and activation
      of neutrophils. Peripheral blood leucocytes were circulated over equal
      concentration mats of ocular surface mucins purified from normal volunteers and
      dry-eye patients, and in sequence over normal and pathological mucins in all
      combinations. Non-adherent cells were tagged with monoclonal fluorescent
      antibodies to leucocyte determinants and analysed by flow cytometry. Oxidative
      burst, assessed with dihydrorhodamine, was followed in cells and supernatant. At
      a speed similar to that of leucocyte traffic in the retina, normal mucins caused
      a decrease in neutrophil cathepsin G fluorescence, a decrease that was not
      observed with mucins from patients with Meibomian gland disease or Sjogren
      syndrome. No effect was detected at a higher flow. Supernatant and cells
      collected after circulation over normal mucin showed increased rhodamine
      fluorescence, indicative of oxidative burst. Fluorescence could also be observed
      in intact cells adherent to dry-eye mucins. Non-adherent cells could be activated
      with phorbol 12-myristate 13-acetate after flow over any mucin or combination of
      mucins. Differences in neutrophil activation after exposure to normal and
      pathological mucins highlight reciprocal influences at the interface between
      local and systemic immunity.

PMID- 15490243
TI  - Ultrastructure of the abdominal sense organ of the scallop Mizuchopecten
      yessoensis (Jay).
AB  - The sensory epithelium of the abdominal sense organ (ASO) of the scallop
      Mizuchopecten yessoensis is composed of three cell types, sensory cells, mucous
      cells, and multiciliated cells. Sensory cells bear a single long (up to 250
      microm) cilium surrounded by an inner ring of nine modified microvilli and an
      outer ring of ordinary microvilli paired with modified microvilli. Sensory cells
      make up about 90% of the total number of cells in the sensory epithelium. Mucous
      cells, which are much wider than sensory cells, bear only ordinary microvilli on
      their apical surface. Rare multiciliated cells with short (4-6 microm) cilia are
      scattered in the periphery of the sensory epithelium sheet. All hairs, cilium,
      and microvilli of each sensory cell are interconnected by a fibrous network. Nine
      modified microvilli of a single cell are interconnected by prominent laterally
      running fibrous links. Membrane-associated electron-dense material of modified
      microvilli is connected to the ciliary membrane-associated electron-dense
      material by fine string-like links. These links mechanically bridge the space
      between the cilium and modified microvilli, as do mechanical links, described for
      the stereocilia and kinocilium of vertebrate vestibular and cochlear hair cells.
      The proximal portion of a sensory cilium is about 100 microm long and has a
      typical 9 x 2+2 axoneme arrangement. The distal portion of a cilium is
      approximately 2 times thinner than the proximal one and is filled with
      homogeneous electron-dense material. Along the distal portion, diffuse material
      associated with the external surface of the membrane is found. The rigidity of
      distal portion of a cilium is much less than that of the proximal one.

PMID- 15490244
TI  - The response of carabids to landscape simplification differs between trophic
      groups.
AB  - We studied the response of carabid species richness and density to landscape
      simplification (measured as percentage cover of non-crop habitat surrounding each
      study site) in 36 wheat fields using pitfall traps. Carabids were divided to
      trophic groups following the literature. The number of species from different
      trophic groups declined with increasing landscape simplification in the order:
      carnivores > phytophages > omnivores. Density compensation of both carnivores and
      phytophages suggests that species decline is caused by the loss of specific
      resources rather than by an overall reduction in food availability. Increasing
      evenness indicates that a greater share of phytophagous species contributes to
      density compensation at poorer sites. A comparison with data from complementing
      studies shows that marked differences in species numbers (carnivores > omnivores
      > phytophages) are due to a different sensitivity of trophic groups to
      agricultural management. Since our findings seem to be partly due to increasing
      sensitivity to landscape changes with trophic rank, and partly to decreasing
      sensitivity of depauperate communities to local environmental stress, species
      loss can best be explained by the co-action of factors at local and regional
      scales. Species richness decline might significantly alter the role of carabids
      as biocontrol agents.

PMID- 15490245
TI  - Microbial dynamics and carbon and nitrogen cycling following re-wetting of soils
      beneath two semi-arid plant species.
AB  - Sporadic summer rainfall in semi-arid ecosystems can provide enough soil moisture
      to drastically increase CO(2) efflux and rates of soil N cycling. The magnitudes
      of C and N pulses are highly variable, however, and the factors regulating these
      pulses are poorly understood. We examined changes in soil respiration, bacterial,
      fungal and microfaunal populations, and gross rates of N mineralization,
      nitrification, and NH(4) (+) and NO(3) (-) immobilization during the 10 days
      following wetting of dry soils collected from stands of big sagebrush (Artemisia
      tridentata) and cheatgrass (Bromus tectorum) in central Utah. Soil CO(2)
      production increased more than tenfold during the 17 h immediately following
      wetting. The labile organic C pool released by wetting was almost completely
      respired within 2-3 days, and was nearly three times as large in sagebrush soil
      as in cheatgrass. In spite of larger labile C pools beneath sagebrush, microbial
      and microfaunal populations were nearly equal in the two soils. Bacterial and
      fungal growth coincided with depletion of labile C, and populations peaked in
      both soils 2 days after wetting. Protozoan populations, whose biomass was nearly
      3,000-fold lower than bacteria and fungi, peaked after 2-4 days. Gross N
      mineralization and nitrification rates were both faster in cheatgrass soil than
      in sagebrush, and caused greater nitrate accumulation in cheatgrass soil. Grazing
      of bacteria and fungi by protozoans and nematodes could explain neither temporal
      trends in N mineralization rates nor differences between soil types. However, a
      mass balance model indicated that the initial N pulse was associated with
      degradation of microbial substrates that were rich in N (C:N <8.3), and that
      microbes had shifted to substrates with lower N contents (C:N =15-25) by day 7 of
      the incubation. The model also suggested that the labile organic matter in
      cheatgrass soil had a lower C:N ratio than in sagebrush, and this promoted faster
      N cycling rates and greater N availability. This study provides evidence that the
      high N availability often associated with wetting of cheatgrass soils is a result
      of cheatgrass supplying substrates to microbes that are of high decomposability
      and N content.

PMID- 15490246
TI  - Mosses and the struggle for light in a nitrogen-polluted world.
AB  - The impact of reduced light conditions as an indirect effect of nitrogen (N)
      deposition was determined on three mosses in a montane ecosystem, where sedge and
      grass cover increase due to N enrichment. Additionally, in the greenhouse we
      established the importance of low light to moss growth as an indirect N
      deposition effect relative to the direct toxic effects of N. The amount of light
      reaching the moss layer was strongly and negatively related to graminoid
      abundance. Mosses showed differing sensitivities to reduced light in the field.
      Racomitrium lanuginosum biomass was found to be highest under high-light
      conditions, Polytrichum alpinum at intermediate light levels, whilst that of
      Dicranum fuscescens was unrelated to light availability. Moreover, Racomitrium
      biomass decreased with increasing amounts of graminoid litter, whereas the other
      species were little affected. All three mosses responded differently to the
      combination of elevated N (20 vs 10 kg N ha(-1) year(-1)) and reduced light (60
      and 80% reduction) in the greenhouse. Racomitrium growth was strongly influenced
      by both light reduction and elevated N, in combination reducing shoot biomass up
      to 76%. There was a tendency for Dicranum growth to be modestly reduced by
      elevated N when shaded, causing up to 19% growth reduction. Polytrichum growth
      was not influenced by elevated N but was reduced up to 40% by shading. We
      conclude that competition for light, induced by vascular plants, can strongly
      influence moss performance even in unproductive low biomass ecosystems. The
      effects of reduced light arising from N pollution can be as important to mosses
      as direct toxicity from N deposition. Yet, different sensitivities of mosses to
      both toxic and shading effects of elevated N prevent generalisation and can lead
      to competitive species replacement within moss communities. This study
      demonstrates the importance of understanding moss-vascular plant interactions to
      allow interpretation and prediction of ecosystem responses to anthropogenic
      drivers such as atmospheric N deposition or climate change.

PMID- 15490248
TI  - Hypophosphatemia in meningococcal sepsis.

PMID- 15490249
TI  - Acceptability of a reformulated renal-specific micronutrient supplement.

PMID- 15490250
TI  - Low nephron number--a new cardiovascular risk factor in children?
AB  - There is increasing evidence that primary hypertension, coronary heart disease,
      and other aspects of the so-called metabolic syndrome that develop in adulthood
      are primed in fetal life or early postnatally. The identification of this
      phenomenon, also known as prenatal or fetal programming, and the detailed
      characterization of the underlying pathomechanisms will greatly influence the
      understanding of these diseases. The present paper reviews recent experimental
      and clinical evidence that low nephron number, found in patients with renal
      dysplasia and low birth weight, is a risk factor for cardiovascular disease in
      later life. Therefore, it is important to identify children at risk as early as
      possible in order to treat them early and to prevent the development of end-organ
      damage. This could be an important goal for pediatrics in the near future.

PMID- 15490251
TI  - Platelet-derived growth factor and platelet profiles in childhood nephrotic
      syndrome.
AB  - The aim of the study was to investigate (1) whether there are any changes in
      release of platelet-derived growth factor AA (PDGF AA) in children with nephrotic
      syndrome without clinical thromboembolic symptoms 2; (2) whether serum PDGF AA
      correlates with the platelet count (PLT) and platelet indices; (3) whether
      prednisone therapy affects the serum PDGF AA and the PLT; (4) whether PDGF AA is
      a useful predictor of disease activity. The study involved two groups of
      children: 33 with nephrotic syndrome (I) who were evaluated twice (A during
      relapse and B after 2 weeks of prednisone treatment) and 34 healthy children
      (II). The serum concentration of PDGF was measured by ELISA. In group I/A the PLT
      (P<0.01) and platelet distribution width (P<0.05) were elevated, the mean
      platelet volume (MPV) (P<0.05) was decreased and the plateletcrit (P>0.05) was
      normal. In group I/B, the PLT was decreased and MPV increased. The concentration
      of PDGF AA was still increased and correlated negatively with the albumin
      concentration. Hence in children with nephrotic syndrome an increase in PLT, a
      decrease in MPV, and a higher concentration of PDGF were observed. Treatment of
      nephrotic syndrome with prednisone for 2 weeks is not sufficient to normalize
      platelet parameters. Further studies are necessary to confirm the role of PDGF AA
      in the hypercoagulation state in children with nephrotic syndrome.

PMID- 15490252
TI  - Transforming growth factor-beta1 in nephrotic syndrome treated with cyclosporine
      and ACE inhibitors.
AB  - The aim of the study was to assess urinary transforming growth factor (TGF)-beta1
      in children with steroid-dependent nephrotic syndrome (SDNS) treated with
      cyclosporine A (CyA) and ACE inhibitors (ACEI). The study involved 24 children
      (14 boys and 10 girls) with SDNS and signs of focal segmental glomerulosclerosis.
      The children were treated with prednisone, CyA, and ACEI. All children were
      examined four times: A during relapse of proteinuria, before treatment with CyA
      and ACEI, and B after 3 months, C 6 months, and D 12 months of treatment. The
      control group consisted of 20 healthy children of the same age. The urinary TGF
      beta1 level was determined by ELISA (R and D Quantikine). The serum CyA level was
      measured by monoclonal antibody fluorescence polarization immunoassay. Prior to
      CyA treatment, the urinary TGF-beta1 level was the highest (135.61+/-38.31 pg/mg
      creatinine). During CyA treatment, TGF-beta1 was reduced to 117.96+/-81.57 after
      3 months, to 80.26+/-49.52 after 6 months, and to 44.00+/-31.83 pg/mg creatinine
      after 12 months, but it was still higher than in the control group. At 3 months
      there was a positive linear correlation between urinary TGF-beta1 and proteinuria
      (r=0.654, P<0.01). These results indicate that the urinary TGF-beta1 level
      increases in proportion to proteinuria during relapse of NS. Treatment with CyA
      and ACEI also influences urinary TGF-beta1, which is still higher after 12 months
      of treatment than in healthy children.

PMID- 15490253
TI  - Adequacy of urinary tract infection management among minority underserved
      children.
AB  - Urinary tract infection (UTI) is one of the common bacterial infections in
      children and may lead to substantial morbidity. This study examines (1) the
      frequency of the performance of follow-up urine cultures and imaging studies for
      children diagnosed with UTI and (2) the relationship of the demographic and
      insurance status of patients with the management and follow-up of UTI. We
      conducted a retrospective chart review of children with first-time documented UTI
      at six different county medical center satellite outpatient clinics and hospital
      based pediatric outpatient walk-in clinics, serving an indigent minority
      community, from January 1998 to December 2000. We identified 144 children with
      confirmed UTI. Of 144 subjects in our study, 44% had follow-up urine cultures and
      43% of these children showed continued infection after a full course of
      antibiotics. Renal ultrasonography and voiding cystourethrogram were performed in
      53% and 39% of children, respectively. Of those patients who did not receive
      follow-up imaging, 67% had no documentation for follow-up appointments. However,
      in 29% of cases attempts had been made to contact patients who were scheduled for
      follow-up, but they did not return for the studies. These data suggest there is a
      significant failure rate for the follow-up of pediatric UTI. There is need for
      educational intervention among pediatricians who provide medical care to
      ethnically diverse underserved, often uninsured, minority children. This
      intervention should reinforce compliance with the standard recommendations for
      appropriate UTI follow-up studies and imaging and provide realistic strategies
      for achieving recommended outcomes in these high-risk populations.

PMID- 15490255
TI  - Structural features of mycorrhizal associations in two members of the
      Monotropoideae, Monotropa uniflora and Pterospora andromedea.
AB  - Species in the subfamily Monotropoideae (family Ericaceae) are achlorophyllous
      and myco-heterotrophic. They have become highly specialized in that each plant
      species is associated with a limited number of fungal species which in turn are
      linked to autotrophic plants. This study provides an updated and comprehensive
      examination of the anatomical features of two species that have recently received
      attention with respect to their host-fungal specificity. Root systems of
      Monotropa uniflora and Pterospora andromedea collected from the field were
      characterized by light microscopy and scanning electron microscopy. All roots of
      both species were associated with fungi, each root having a well-developed
      mantle, paraepidermal Hartig net, and intracellular "fungal pegs" within
      epidermal cells. The mantle of M. uniflora was multi-layered and numerous outer
      mantle hyphae developed into cystidia of two distinct morphologies. Large calcium
      oxalate crystals were present, primarily on the mantle surface. The outer mantle
      of P. andromedea was more loosely organized, lacked cystidia, and had smaller
      plate-like as well as cylindrical crystals on the surface and between outer
      mantle hyphae. Fungal pegs in M. uniflora originated from inner mantle hyphae
      that penetrated the outer tangential wall of epidermal cells; in P. andromedea,
      these structures were initiated either from inner mantle hyphae or Hartig net
      hyphae and penetrated radial walls of epidermal cells. With respect to function,
      fungal pegs occurred frequently in both host species and, although presumed to be
      the sites of active nutrient exchange, no direct evidence exists to support this.
      Differences between these two monotropoid hosts, resulting from the mycorrhizal
      fungi with which each associates, are discussed.

PMID- 15490257
TI  - The 23rd Annual Working Group in Interventional Neuroradiology (WIN) - Val
      D'Isere, France, January 13th-16th 2004.

PMID- 15490256
TI  - Functional results and the risk factors of reoperations after lumbar disc
      surgery.
AB  - Factors such as driving motor vehicles, sedentary occupations, vibration,
      smoking, previous full-term pregnancies, physical inactivity, increased body mass
      index (BMI), and a tall stature are associated with symptomatic disc herniations.
      Fitness and strength is postulated to protect an individual from disc rupture.
      The objective of our study was to determine the pain levels and differences of
      functional and economic situations of patients who had undergone one or more than
      one operation due to lumbar disc herniation and to put forward the effect of risk
      factors that may be potential, especially from the aspect of undergoing
      reoperation. Patients who had undergone one (n=46) or more than one operation
      (n=34) due to lumbar disc herniation were included in the study. It was a
      prospective study with evaluation on the day the patients were discharged and at
      second and sixth months after lumbar disc operation. The Oswestry Disability
      Index (ODI) was used in determining the functional disability associated with
      back pain; the Prolo Functional Economic Rating Scale (Prolo scale) was used in
      determining the effect of back pain on functional and economic situations. In the
      ODI measurements made in the postoperative second and sixth months, significant
      differences appeared in favor of patients who had undergone one operation
      (p<0.05). According to the Prolo scale, it was found that the economic situation
      was better in the sixth month and the functional situation was better in the
      second and sixth months in patients having undergone one operation (p<0.05). The
      logistic regression analysis demonstrated that the lack of regular physical
      exercise was a significant predictor for reoperation (OR, 4.595; CI, 1.38-15.28),
      whereas gender, age, BMI, occupation, or smoking did not indicate so much
      significance as regular exercise.

PMID- 15490259
TI  - Polyamines biosynthesis and oxidation in free-living amoebae.
AB  - In this paper we describe the polyamine biosynthesis and oxidation processes,
      giving an overview about recent results in free-living Amoebae. The protozoa
      polyamine levels are different in comparison with mammalian cells. Also, the
      polyamine levels in protozoa cells change if these species are pathological or
      not for the human beings. All the amoeba strains show high concentrations of 1,3
      diaminopropane (DAP), spermidine and acetylspermidine while spermine is absent.
      In these amoeba a considerable polyamine oxidase activity has been found, which
      acts on N8-acetylspermidine, but not on free polyamines. This enzyme is
      responsible, together with polyamine acetylase, of DAP synthesis whose function
      is not well known.

PMID- 15490260
TI  - Evolution of understanding of genetics of Paget's disease of bone and related
      diseases.

PMID- 15490261
TI  - Osteocytic osteolysis observed in rats to which parathyroid hormone was
      continuously administered.
AB  - In order to prove osteocytic osteolysis in vivo, human parathyroid hormone (hPTH
      (1-34), 749 ng/h), or only solvent of the same volume, was continuously
      administered to 8-month-old rats by an infusion pump for 4 weeks, and then
      structural changes in osteocytes in the cortical bones of the tibiae were
      analyzed morphometrically, histologically, and histochemically. Based on contact
      microradiography (CMR) observations, the osteocyte lacunae in the PTH group
      tended to be enlarged, compared with those of the control, while the average
      lacuna area was 137.0 microm2 in the PTH group versus 93.9 microm2 in the
      control, suggesting evidence of osteocytic osteolysis. Acid phosphatase enzyme
      histochemical localization was observed in some osteocytes in the PTH group;
      therefore, lysosome systems may participate in the osteolytic mechanisms. On
      histological samples stained with hematoxylin-eosin or toluidine blue, the
      lacunae of the controls were surrounded by narrow areas of matrices both positive
      for hematoxylin and metachromatic for toluidine blue, while belt-like areas
      positive for hematoxylin were observed around the PTH-group lacunae. These
      findings suggested that, after osteocytic osteolysis, regenerated bone matrices
      may be added to the walls of osteocytes that possess enlarged lacunae.

PMID- 15490262
TI  - Human parathyroid hormone (1-34) increases mass and structure of the cortical
      shell, with resultant increase in lumbar bone strength, in ovariectomized rats.
AB  - Estrogen deficiency causes reduction of bone mass and abnormal bone
      microarchitecture, consequently reducing bone strength. Human parathyroid hormone
      (hPTH) (1-34) increases bone mass and strength. To clarify the factors that
      determine the recovery of bone strength in the lumbar vertebrae of ovariectomized
      rats by intermittent hPTH administration, we analyzed the relationship between
      skeletal measurements and bone strength. Human PTH (1-34) administration resulted
      in recovery of cortical bone mineral content (BMC) and cortical bone area to sham
      the levels, but in resulted in a less pronounced recovery of trabecular BMC and
      no increase in the total cross-sectional area of the vertebral body. Of the three
      dimensional (3D) trabecular bone parameters, hPTH (1-34) increased trabecular
      thickness (Tb.Th). The cortical shell area of L4, determined by histomorphometry,
      was also increased. In hPTH-treated rats, the only determinant of the compressive
      load of L5 was the cortical shell BMC, in the early recovery period (days 42-84).
      Our data suggest that increased cortical bone mass contributes more than
      trabecular bone mass and structure to the recovery of bone strength in response
      to hPTH therapy in the rat lumbar vertebral body after ovariectomy.

PMID- 15490263
TI  - Local injection of 1,25-dihydroxyvitamin D3 enhanced bone formation for tooth
      stabilization after experimental tooth movement in rats.
AB  - The present investigation evaluated the effect of 1,25-dihydroxyvitamin D3
      (1,25(OH)2D3) on alveolar bone formation during tooth movement in rats.
      Orthodontic elastics were inserted between the maxillary first and second molars
      on bilateral sides in male rats. 1,25(OH)2D3 was injected locally, at the
      concentration of 10(-10) M, once every 3 days in the submucosal palatal area of
      the root bifurcation of the molar on the right side. Histomorphometric analysis
      revealed that tooth movement without application of 1,25(OH)2D3 decreased the
      mineral appositional rate (MAR) on the compression area at 7 days. Repeated
      injections of 1,25(OH)2D3 in the orthodontically treated animals distinctly
      stimulated alveolar bone formation on the mesial side at 14 days. There was a
      significant increase in MAR associated with elevated osteoblast surface (Ob.S/BS)
      value on the tension surface. These findings suggest that local application of
      1,25(OH)2D3 enhances the reestablishment of supporting tissue, especially
      alveolar bone of teeth, after orthodontic treatment.

PMID- 15490264
TI  - Assessment of effectiveness of oral administration of collagen peptide on bone
      metabolism in growing and mature rats.
AB  - The purpose of this study was to examine the effectiveness of collagen peptide
      intake on bone metabolism in growing (G) and calcium-deficient mature (M) rats.
      As for the dosages used, they were amounts equal to the recommended supplements
      for humans (0.166 g/kg body weight (BW) per day: Coll-1G and Coll-1M groups), 10
      fold higher (1.66 g/kg BW per day: Coll-10G and Coll-10M groups), and 100-fold
      higher (16.6 g/kg BW per day: Coll-100G group). In growing male rats, bone
      mineral density (BMD) of the femur in the Coll-100G group was significantly
      higher than that in the other groups after the 4-week experimental period. On the
      other hand, kidneys in the rats from the Coll-100G group exhibited hypertrophy.
      To examine the effects of collagen peptide on bone metabolism in a calcium
      deficient status, mature female rats were fed a 0.01% Ca diet for 9 weeks and
      then fed a diet with 0.2% calcium with or without collagen peptide (control, Coll
      1M, and Coll-10M groups) or a 0.5% calcium diet (normal Ca) for 8 weeks. BMD of
      the whole femur in the Coll-10M group was significantly higher than that in the
      control and Coll-1M groups, and the level was similar to that in the normal Ca
      group. BMD of the lumbar spine in the Coll-10M group was significantly higher
      than their baseline value, as well as being significantly higher than that in the
      control and Coll-1M groups. These results suggest that orally administered
      collagen peptide may provide beneficial effects on bone metabolism, especially in
      the calcium-deficient condition, without obvious undesirable effects.

PMID- 15490265
TI  - Regulation of bone metabolism in immunosuppressant (FK506)-treated rats.
AB  - After organ transplantation, severe osteoporosis is occasionally seen, and the
      use of immunosuppressants is thought to be one of the causes of such
      osteoporosis. In the present study, we investigated the effects of FK506
      monotherapy on bones and determined the mechanism of onset of osteoporosis, both
      by assessing chronological changes in bone metabolism and by identifying factors
      that facilitate bone resorption. In 8-week-old male Sprague-Dawley rats, FK506 (1
      mg/kg) was injected intraperitoneally every day for 5 weeks (FK506-treated
      group), and for comparison, physiological saline was administered in the same
      manner in a control group of rats. Serum and urine samples were collected at
      weeks 0, 1, 3, and 5 of administration. The femur and tibia were collected within
      24 h of the final administration. When compared to the control group, findings on
      three-dimensional micro-computed tomography of the femur for the FK506-treated
      group showed a significant decrease in trabecular bone volume. The level of serum
      osteocalcin in the FK506-treated group at week 1 of administration was
      significantly higher than the control. Throughout the administration period, the
      sum of urinary pyridinoline (PYD) and deoxypyridinoline (Dpd) was significantly
      higher in the FK506-treated group. Of the various bone resorption factors tested,
      the level of serum parathyroid hormone (PTH) in the FK506-treated group was
      significantly higher than the control at week 3 of administration. The results of
      the present study confirmed that FK506 monotherapy in rats induced high-turnover
      osteoporosis. Soon after the start of FK506 administration, bone formation and
      resorption were elevated, and PTH appeared to have been involved in the
      maintenance of the elevated bone resorption.

PMID- 15490266
TI  - Effect of dietary-induced metabolic acidosis and ovariectomy on bone mineral
      density and markers of bone turnover.
AB  - Dietary-induced metabolic acidosis (DIMA) has been implicated as a significant
      confounder in the development of osteoporosis. Twenty-four mature ewes were
      randomly assigned to four groups of six sheep. Group 1 consumed a control diet
      (ND); group 2 consumed a normal diet (ND) and had ovariectomy (OVX), group 3
      consumed a diet that induced metabolic acidosis (MA), without OVX, and group 4
      consumed a diet that induced MA, with OVX. The study was conducted over 180 days
      and the sheep were maintained on the assigned diet throughout. Sheep were weighed
      and bone mineral density (BMD) was measured, using dual-energy X-ray
      absorptiometry (DEXA), on days 0 and 180. Serum bone alkaline phosphatase (BAP),
      urine deoxypyridinoline (DPD), and fractional excretions (FE) of Ca and P were
      determined on days 0, 90, and 180. Arterial blood pH was determined on day 180.
      Analysis consisted of a two-way analysis of variance for repeated measures with
      significance set at P < or = 0.05. Body weights, serum BAP, and urine DPD were
      not influenced by either diet or OVX status. DIMA did significantly increase
      urinary FE of Ca and P and significantly decreased lumbar BMD and arterial pH.
      Arterial pH remained within physiologic normal limits. DIMA was a more potent
      cause of calcium wasting than OVX over the time frame of this study. Sheep appear
      to be sensitive to DIMA and will therefore be a useful animal model to study the
      influence of diet on the development of osteoporosis. The specific mechanisms
      through which DIMA exerts its influence are still unknown and are the subject of
      ongoing studies.

PMID- 15490267
TI  - Effect and safety of intermittent weekly administration of human parathyroid
      hormone 1-34 in patients with primary osteoporosis evaluated by histomorphometry
      and microstructural analysis of iliac trabecular bone before and after 1 year of
      treatment.
AB  - In order to evaluate the efficacy and safety of intermittent subcutaneous
      administration of 1-34 N-terminal peptide of human parathyroid hormone (hPTH 1
      34), 100 units of hPTH 1-34 was subcutaneously injected once a week for 1 year in
      ten patients with primary osteoporsis (one male and nine females) with no
      qualitative abnormality of the bone according to the results of iliac crest
      biopsy performed previously, followed by a second biopsy after the end of the 1
      year administration. Written consent of the patients for participation in the
      study was obtained. The mean lumbar bone mineral density (LBMD) definitely
      increased, by 1.8%, 3.4%, and 4.6% after 12, 24, and 48 weeks of hPTH
      administration, in accordance with previous clinical studies. Histomorphometric
      analysis after double-tetracycline labeling was completed in six patients (one
      male and five females) after the exclusion of those who dropped out because of
      adverse events unrelated to the test drug, or refusal of continuation.
      Examination of thin hard-tissue sections revealed no qualitative abnormalities of
      bone tissue or bone marrow cavity, such as osteomalacia, woven bone, or osteitis
      fibrosa, precluding the contribution of qualitatively abnormal tissue elements to
      any changes of LBMD in response to hPTH 1-34 administration. Histomorphometric
      measurement in the second biopsy revealed a tendency for an increase of bone
      volume, a significant increase of osteoid surface, and a tendency for an increase
      in other parameters of bone formation, compared with values obtained in the
      preadministration biopsy. Indices of two-dimensional microstructure obtained by
      microfocus computed tomography (CT) and results of node-strut analysis indicated
      improvement of trabecular continuity. In five patients in whom three-dimensional
      reconstruction images were analyzed, there were significant increases of bone
      volume and trabecular thickness, and a significant decrease in the trabecular
      bone pattern factor, a parameter related to the continuity, suggesting an
      improvement of the three-dimensional trabcular microstructure. Intermittent
      weekly subcutaneous injections of hPTH (1-34) for 48 weeks increased trabecular
      bone volume and improved microstructure, without causing the appearance of
      abnormal bone elements in primary osteoporosis.

PMID- 15490268
TI  - Alendronate reduces serum TNFalpha and IL-1beta, increases neutrophil counts, and
      improves bone mineral density and bone metabolism indices in patients with
      chronic idiopathic neutropenia (CIN)-associated osteopenia/osteoporosis.
AB  - The current study was undertaken to investigate the effect of alendronate on bone
      mineral density (BMD), bone metabolism markers, and serum bone-resorbing
      cytokines in patients with chronic idiopathic neutropenia (CIN)-associated
      osteopenia/osteoporosis. Sixteen randomly selected women, 7 with CIN-associated
      osteoporosis and 9 with CIN-associated osteopenia, and 14 age- and menopausal
      status-matched healthy volunteers, were enrolled in the study. Patients received
      10 mg alendronate daily per os for 360 days and studies were done before
      treatment (day 0) and at varying time points during the study. We found that
      patients' BMD measurements increased by 5.32% after treatment, and that the
      elevated serum osteocalcin (OC), a bone formation marker, decreased by day 30,
      normalized by day 90, and increased again by day 270 of treatment. Elevated
      values of patients' urine deoxypyridinoline (Dpd) and N-telopeptide of type I of
      collagen (NTx), two bone resorption markers, returned to the control range by day
      30 and decreased thereafter. Increased levels of patients' serum tumor necrosis
      factor-alpha (TNFalpha) and interleukin-1beta (IL-1beta), two bone resorbing
      cytokines, returned to the control range by day 30 and decreased thereafter.
      Peripheral blood neutrophil counts increased by day 30 and continued to rise
      thereafter, reaching a mean value higher than 2650 neutrophils per microl of
      blood on day 360. Interestingly, alendronate-induced changes in the levels of
      both cytokines correlated inversely with the respective changes in neutrophil
      counts and BMD measurements, and positively with the changes in the respective
      means of urine NTx and Dpd values. All these findings indicate that alendronate
      is effective in treating CIN-associated osteopenia/osteoporosis, and that the
      beneficial effect of the compound may lie, at least in part, in its property to
      inhibit the production of TNFalpha and IL-1beta by cells of the
      monocyte/macrophage system, in which osteoclasts are included.

PMID- 15490269
TI  - Precision control and seasonal variations in quantitative ultrasound measurement
      of the calcaneus.
AB  - To assess the dependence of calcaneal quantitative ultrasound (QUS) indices
      (speed of sound [SOS] and broadband ultrasound attenuation [BUA]) on foot
      temperature and season, we measured these indices monthly, from August to
      February of the next year, in five healthy Japanese adults (three men and two
      women, aged 31-52 years), using a dry-type QUS device (Sahara; Hologic). The
      monthly QUS measurement was performed three consecutive times after the start, at
      30, 60, and 120 min from the start, in a test room where the temperature was kept
      at 25 +/- 2 degrees C. Skin temperature was monitored at the dorsum pedis
      throughout the measurements. A significant seasonal trend in the monthly mean Z
      scores of QUS indices was observed (P < 0.001). QUS indices were higher during
      the winter than summer, while skin temperatures were lower during the winter. SOS
      showed a significant inverse association with skin temperature (r = -0.64), while
      BUA did not (r = 0.09). Skin temperature at the dorsum pedis slowly declined and
      SOS increased during the experiment. BUA decreased by 60 min from the start of
      the experiment and then increased slightly. The coefficient of variation (CV) of
      both QUS indices showed the smallest values at 60 min from the start. In
      conclusion, there are seasonal variations in the QUS indices, and SOS
      particularly depends on skin temperature. When a subject is followed up for
      years, the QUS measurements should be conducted in the same season. In a setting
      of community-based medical checkups using QUS devices, health professionals
      should measure the QUS indices of a subject after 60 min of rest in the
      examination room.

PMID- 15490270
TI  - The serum level of bone-specific alkaline phosphatase activity is associated with
      aortic calcification in osteoporosis patients.
AB  - It has been suggested that there are several possible linkages between vascular
      calcification and osteoporosis. In addition, the processes of vascular
      calcification may have a common etiology with bone formation. Thus, we
      hypothesized that the serum levels of bone metabolic markers would be different
      between osteoporosis patients with and without vascular calcification. In this
      study, we showed that the serum level of bone-specific alkaline phosphatase
      activity in osteoporosis patients with abdominal aortic calcification had a
      higher value than in those without the calcification. On the other hand, there
      were no significant differences in the urine levels of type I collagen cross
      linked N-telopeptides (a bone resorption marker), or in the serum levels of
      intact osteocalcin, Ca, and P. Bone-specific alkaline phosphatase is the most
      important marker for osteoblast differentiation; furthermore, the serum level of
      its activity may reflect the process of calcification of the aorta in
      osteoporosis patients.

PMID- 15490271
TI  - Bone density changes with enzyme therapy for Gaucher disease.
AB  - Gaucher disease is the most common lysosomal storage disease. Enzyme replacement
      therapy engenders improvement in hematological and visceral parameters; however,
      improvement in bone density (BMD) with treatment has not been confirmed. This
      study presents follow-up of BMD in the first ten patients in Israel treated with
      low-dose recombinant enzyme for up to 108 months. BMD at femoral neck and lumbar
      spine was determined by dual-energy X-ray absorptiometry (DEXA) at the start of
      the trial, after 3-6 months, after 18-24 months, and at the most recent follow
      up. BMD in all patients was very low at onset and never normalized. There was a
      decrease in BMD in all patients at 3-6 months. Older patients (four women, two
      men; >30 years of age) showed some improvement in BMD during treatment. Younger
      patients (four females; 18-23 years of age) did not show a statistically
      significant improvement. These findings might reflect the failure of patients
      with Gaucher disease to achieve expected peak bone density at appropriate
      chronological milestones despite treatment. Nonetheless, the z-scores of the
      older patients were better than those of the younger patients, implying some
      catch-up period. Yet, some patients with Gaucher disease evince rapid onset of
      osteoporosis in early adulthood. Enzyme treatment per se, as well as attendant
      improved well-being and increased physical activity, may induce amelioration in
      BMD at this later stage. One may consider adding anti-osteoporosis therapy in
      young adults to induce earlier "catch up" to peak bone mass, and then enzyme
      replacement in later adulthood to prevent decrements in bone mass related to
      Gaucher cell infiltration.

PMID- 15490272
TI  - Randomized controlled trial of exercise intervention for the prevention of falls
      in community-dwelling elderly Japanese women.
AB  - Falls are common in elderly people. Possible consequences include serious
      injuries and the post-fall syndrome, with functional decline and limitation of
      physical activity. The present randomized controlled study sought to clarify the
      benefits of a combined long-term and home-based fall prevention program for
      elderly Japanese women. The subjects were individuals aged over 73 years, living
      at home in a western suburb of Tokyo, who had attended a comprehensive geriatric
      health check. Persons with a marked decline in the basic activities of daily
      living (ADL), hemiplegia, or those missing baseline data were excluded. Fifty-two
      subjects who expressed a wish to participate in the trial were randomized, 28 to
      an exercise-intervention group and 24 to a control group. Baseline data for age,
      handgrip force, walking speed, total serum cholesterol, serum albumin, basic ADL,
      visual and auditory impairments, self-rated health, and experience of falls did
      not differ significantly between the two groups. Beginning from June 2000, the
      intervention group attended a 6-month program of fall-prevention exercise classes
      aimed at improving leg strength, balance, and walking ability; this was
      supplemented by a home-based exercise program that focused on leg strength. The
      control group received only a pamphlet and advice on fall prevention. The average
      rate of attendance at exercise class was 75.3% (range, 64% to 86%). Participants
      showed significant improvements in tandem walk and functional reach after the
      intervention program, with enhanced self confidence. At the 8-month follow-up,
      the proportion of women with falls was 13.6% (3/22) in the intervention group and
      40.9% (9/22) in the control group. At 20 months, the proportion remained
      unchanged, at 13.6% in the intervention group, but had increased to 54.5% (12/22)
      in the control group, which showed a statistically significant difference between
      the two groups (Fisher's exact test; P = 0.0097). The total number of falls
      during the 20-month follow-up period was 6 in the intervention group and 17 in
      the control group. We conclude that a moderate exercise intervention program plus
      a home-based program significantly decreases the incidence of falls in both the
      short and the long term, contributing to improved health and quality of life in
      the elderly.

PMID- 15490273
TI  - Dietary habits and risk of ossification of the posterior longitudinal ligaments
      of the spine (OPLL); findings from a case-control study in Japan.
AB  - The relation between dietary habits and the risk of ossification of the posterior
      longitudinal ligaments of the spine (OPLL) was investigated in a case-control
      study conducted in Japan from 1998 to 2001. Prevalent OPLL cases (n = 69) were
      identified and individually matched by age and sex with community controls (n =
      138) randomly selected from the general population in Hokkaido. A self
      administered food-frequency questionnaire was used to assess habitual dietary
      intake. The odds ratio (OR) and its 95% confidence interval (CI) were estimated,
      using conditional logistic regression models to compute the OR adjusted for a
      history of diabetes mellitus. We found that frequent consumption of pickles
      (salted products) was significantly associated with an increased risk of OPLL,
      with an adjusted OR of 1.6 (95% CI, 1.1 to 2.2). The adjusted OR for nondaily
      consumers of rice was 3.0 (95% CI, 2.4 to 3.7). Frequent consumption of chicken
      (adjusted OR, 0.5; 95% CI, 0.3 to 0.98) and soy foods (adjusted OR, 0.4; 95% CI,
      0.2 to 0.7) was significantly associated with a decreased risk of OPLL. Our
      findings suggest that dietary habits may constitute independent risk factors for
      OPLL. Further studies will be needed to prospectively determine the relationship
      between dietary habits and OPLL risk.

PMID- 15490274
TI  - Changes in biochemical markers of bone in patients with insufficiency fractures.
AB  - Twelve patients presented at our department with low back or buttock pain and
      were diagnosed as suffering from insufficiency fracture. All patients were
      evaluated with plain radiographs, magnetic resonance imaging, and/or bone
      scintigraphy. We also measured biochemical markers of bone turnover in these
      patients. Bone scintigraphy revealed a high uptake in the fracture site in all
      patients with insufficiency fracture. Biochemical markers of bone turnover were
      significantly increased in all patients, but decreased after the fracture healed
      and the pain was resolved. In those patients who complained of pain again, the
      biochemical markers of bone turnover had increased once more, and bone
      scintigraphy showed a new fracture at a different site. Because the changes in
      bone turnover markers were closely related to clinical symptoms of insufficiency
      fracture, we speculated that repeated measurements of bone turnover markers may
      be informative for discriminating insufficiency fracture from bone metastasis.

PMID- 15490276
TI  - Risk factors for eating disorders in adolescents. A Spanish community-based
      longitudinal study.
AB  - OBJECTIVE: The aim of this study was to identify psychopathological, social and
      family variables that, measured at the age of 13, might predict the development
      of eating disorders 2 years later, using a standardized interview and controlling
      the effect of initially abnormal eating behavior. METHOD: At age 13 and 15, 1076
      adolescents completed questionnaires for the screening of psychiatric morbidity,
      abnormal eating attitudes and family dysfunction. Probable cases of eating
      disorders [159] and 150 controls were assessed with standardized interviews
      (SCAN). RESULTS: Controlling the effect of previous eating psychopathology,
      pathological body dissatisfaction, measured with the Body Shape Questionnaire
      (BSQ), and a negative perception of parental attitudes were predictors of eating
      disorders 2 years later. Self-esteem was a protective factor for body
      dissatisfaction. CONCLUSIONS: Preventive actions should focus on self-esteem as a
      protective factor for body dissatisfaction, a strong predictor for eating
      disorders. The significance of family perception should be explored more in
      detail in future research.

PMID- 15490275
TI  - Global assessment of psychosocial functioning in child and adolescent psychiatry.
      A review of three unidimensional scales (CGAS, GAF, GAPD).
AB  - Global assessment of functioning represents an important aspect of assessment in
      clinical practice and research. It can help identify persons in need of
      psychiatric treatment, have predictive value and measure change over time,
      including treatment effects. This review examines publications concerning
      development, psychometric properties and usefulness of three scales for children:
      Axis-VI in ICD-10 Global Assessment of Psychosocial Disability (GAPD), Children's
      Global Assessment Scale (CGAS) and Axis-V in DSM-IV Global Assessment of
      Functioning Scale (GAF). It is based on literature searches in PubMed and
      PsycInfo (1977-2003), and screening of Scandinavian and English textbooks on
      child psychiatry. The three scales differ in theoretical guidelines, descriptions
      of codes/anchor points and psychometric aspects. CGAS has been evaluated in 69
      papers and 33 have been published on GAF used for children. The one paper
      comparing GAPD and CGAS found both scales sufficiently reliable for clinical
      practice. Reliability of CGAS and GAF has been found to vary from fair to
      substantial, depending on raters, training and diagnostic groups. International
      consensus for the use of one scale for global assessment of functioning for
      children 4-18 years would improve reliability in clinical practice and ease
      comparisons of studies across countries. A training programme would assist in
      this.

PMID- 15490277
TI  - Good outcome of adolescent onset anorexia nervosa after systematic treatment.
      Intermediate to long-term follow-up of a representative county-sample.
AB  - We studied the intermediate to long-term outcome of childhood and adolescent
      onset anorexia nervosa (AN), in a sample that had received systematic treatment
      based on close cooperation between parents, paediatric department and child and
      adolescent psychiatry. Of 55 female AN-patients, 51 were examined 3.5-14.5 years
      after treatment start. The material includes all AN-patients under 18 years in
      one county that received inpatient treatment and almost all that received
      outpatient treatment, during the time period 1986-1998. Forty-two (82%) subjects
      had no eating disorder (ED) at follow-up, one (2%) had AN, one (2%) bulimia
      nervosa (BN) and seven (14%) had less severe ED (EDNOS). Except the one with BN,
      none had bulimic symptoms. There was no mortality. Twenty (41%) had one or more
      other axis-1 psychiatric diagnoses at follow-up. Depression and anxiety disorders
      were most frequent. Psychosocial functioning assessed by Global Assessment of
      Functioning (GAF) was fairly good; mean 73+/-SD14 for symptoms and mean 77+/-SD13
      for functioning. Only 48% were satisfied with life, compared to 83% in a normal
      population sample. Our conclusion is that the eating disorder outcome was good.
      However, in accordance with other studies, many subjects had other psychiatric
      problems at follow-up.

PMID- 15490278
TI  - The clinical necessity for assessing Attention Deficit/Hyperactivity Disorder
      (AD/HD) symptoms in children with high-functioning Pervasive Developmental
      Disorder (PDD).
AB  - Although the DSM-IV diagnostic criteria for Attention Deficit/Hyperactivity
      Disorder (AD/HD) exclude Pervasive Developmental Disorder (PDD), some clinicians
      find that the two disorders can be comorbid and, in fact, make a dual diagnosis.
      Nevertheless, few empirical studies have investigated the clinical necessity for
      this practice. In the first of our two studies, children with high-functioning
      PDD were selected from among 520 outpatients. Of these, children also meeting the
      DSM-IV criteria for AD/HD were identified through a psychologist's observation,
      the completion of the ADHD-Rating Scale by parents and/or teachers, and a child
      psychiatrist's examination. We then examined the impact of PDD subtype and age on
      the co-occurrence rate. Study 2 analyzed comorbidity in two cases taken from
      Study 1. Of the 53 subjects in Study 1, 36 children also met the DSM-IV criteria
      for AD/HD. The co-occurrence rate for Asperger's Disorder (AS)/Pervasive
      Developmental Disorder, Not Otherwise Specified (PDDNOS) (85%) was significantly
      higher than for Autistic Disorder (57.6 %), and AD/HD symptoms were more common
      in younger children. Study 2 demonstrated the existence of comorbidity of PDD and
      AD/HD as separate disorders. We conclude not only that AD/HD symptoms occur
      frequently in children with PDD, but also that in some cases a dual diagnosis is
      essential to the implementation of effective treatment.

PMID- 15490279
TI  - Attention-deficit/hyperactivity disorder (ADHD): parents' judgment about school,
      teachers' judgment about home.
AB  - OBJECTIVE: The aim of this study was to separate sources of observer and
      situational variance in reporting attention-deficit/hyperactivity disorder (ADHD)
      symptomatology. METHOD: In a sample of 30 children diagnosed with ADHD, ADHD
      symptomatology was assessed with the Diagnostic Interview Schedule for Children
      Parent Version (DISC-P), with parents and teachers as informants. Both parents
      and teachers reported about the child's ADHD symptomatology at home as well as at
      school. RESULTS: Parents and teachers showed high within-observer cross
      situational presence of ADHD symptoms. However, the between-observer agreement on
      the presence of ADHD symptoms within the same situation (home or school) was low.
      This pattern held equally true for attention/concentration and
      hyperactivity/impulsivity symptom scores. CONCLUSIONS: In evaluating ADHD
      symptomatology, it is important to obtain independent reports about the child's
      behaviour at school from the teacher and about the child's behaviour at home from
      the parents.

PMID- 15490280
TI  - Trends in adolescent suicide mortality in the WHO European Region.
AB  - Trends in adolescent suicide rates (15-19 years) from 1979 to 1996 were compared
      with suicide trends in individuals of 20 years and over in 30 countries and with
      trends in rates of deaths due to undetermined causes in adolescents in 17
      countries of the WHO European Region. In 21 of the 30 studied countries, male
      adolescent suicide rates increased during the study period (highest increases in
      Belarus, Kazakstan and Ireland) accompanied by far less increases or decreases in
      suicide rates of males of 20 years and over. Part of the observed increases in
      Sweden, Ireland and Greece can be attributed to improved suicide statistics,
      while increases in Finland, Belgium, Bulgaria and the United Kingdom can be even
      higher due to the rising classification of deaths as "undetermined". In Portugal,
      decreasing suicide trends seem to be misinterpreted by ignoring the vast
      increases in rates of undetermined deaths. Female adolescent suicide rates rose
      less markedly than in males in 18 countries, with the exception of strong
      increases in Norway, Ireland. Increases in female adolescent suicide rates were
      marginally affected by changes in classification practices and were accompanied
      primarily by declining suicide rates in females of 20 years and over.

PMID- 15490281
TI  - SAMe use in children and adolescents.

PMID- 15490283
TI  - Distinctions in adenylate metabolism among organisms inhabiting temperature
      extremes.
AB  - Microbiota from multiple kingdoms (e.g., Eubacteria, Fungi, Protista) thrive at
      temperature optima ranging from 0-20 degrees C (psychrophiles) to 40-85 degrees C
      (thermophiles). In this study, we have monitored changes in adenylate levels and
      growth rate as a function of temperature in disparate thermally adapted
      organisms. Our data indicate that growth rate and adenylate levels increase with
      temperature in mesophilic and thermophilic species, but rapid losses of adenosine
      5'-triphosphate (ATP) occur upon cold or heat shock. By contrast, psychrophilic
      species decrease adenylate levels but increase growth rate as temperatures rise
      within their viable range. Moreover, psychrophilic ATP levels fell rapidly upon
      heat shock, but dramatic gains in ATP (approximately 20-50%) were observed upon
      cold shock, even at sub-zero temperatures. These results suggest that energy
      metabolism in thermophiles resembles that in mesophiles, but that elevated
      adenylate nucleotides in psychrophiles may constitute a compensatory strategy for
      maintaining biochemical processes at low temperature.

PMID- 15490284
TI  - Comparative analysis of surface electrostatic potentials of carbon,
      boron/nitrogen and carbon/boron/nitrogen model nanotubes.
AB  - We have extended an earlier study, in which we characterized in detail the
      electrostatic potentials on the inner and outer surfaces of a group of carbon and
      B(x)N(x) model nanotubes, to include several additional ones with smaller
      diameters plus a new category, C(2x)B(x)N(x). The statistical features of the
      surface potentials are presented and analyzed for a total of 19 tubes as well as
      fullerene and a small model graphene. The potentials on the surfaces of the
      carbon systems are relatively weak and rather bland; they are much stronger and
      more variable for the B(x)N(x) and C(2x)B(x)N(x). A qualitative correlation with
      free energies of solvation indicates that the latter two categories should have
      considerably greater water solubilities. The inner surfaces are generally more
      positive than the corresponding outer ones, while both positive and negative
      potentials are strengthened by increasing curvature. The outsides of B(x)N(x)
      tubes have characteristic patterns of alternating positive and negative regions,
      while the insides are strongly positive. In the closed C(2x)B(x)N(x) systems,
      half of the C-C bonds are double-bond-like and have negative potentials above
      them; the adjacent rows of boron and nitrogens show the usual B(x)N(x) pattern.
      When the C(2x)B(x)N(x) tubes are open, with hydrogens at the ends, the surface
      potentials are dominated by the B+-H- and N(-)-H+ linkages.

PMID- 15490285
TI  - Genome-wide linkage analysis of type 2 diabetes mellitus reconfirms the
      susceptibility locus on 11p13-p12 in Japanese.
AB  - Type 2 diabetes mellitus is a heterogeneous disorder, and the development of type
      2 diabetes mellitus is associated with both insulin secretion defect and insulin
      resistance. The primary metabolic defect leading to type 2 diabetes mellitus has
      been thought to be varied among populations, especially in Japanese and
      Caucasians. Here, we have done the genome-wide scan for type 2 diabetes mellitus
      using 102 affected Japanese sib-pairs to identify the genetic factors
      predisposing to type 2 diabetes mellitus. Nonparametric linkage analysis showed
      one suggestive evidence for linkage to 11p13-p12 [D11S905: two-point maximum LOD
      score (MLS) of 2.89 and multipoint MLS of 2.32] and one nominally significant
      evidence for linkage to 6q15-q16 (D6S462: two-point MLS of 2.02). Interestingly,
      the 11p13-p12 region was reported to be a susceptibility locus for Japanese type
      2 diabetes mellitus with suggestive evidence of linkage, and D11S905 was within 5
      cM to D11S935 with the highest MLS in the previous linkage analysis reported. The
      only overlapped susceptibility region with suggestive evidence of linkage for
      Japanese type 2 diabetes mellitus was D11S935-D11S905 among the three reports
      including this study. These results taken together suggest that a susceptibility
      gene for type 2 diabetes mellitus in Japanese will reside in 11p13-p12.

PMID- 15490286
TI  - Convulsive disorder and genetic polymorphism. Association of idiopathic
      generalized epilepsy with haptoglobin polymorphism.
AB  - Haptoglobin is a polymorphic protein that is well known for its hemoglobin (Hb)
      binding property. The protein shows gross differences in molecular size among
      genotypes, resulting in different degrees of diffusion in central nervous system
      tissue. Since the breakdown of erythrocytes in the intracerebral fluid results in
      Hb-mediated free OH radical formation, lipid peroxidation, and increased neuronal
      excitability, a differential diffusion of haptoglobin phenotypes in the
      intracerebral fluid might result in a different degree of protection from
      oxidative damage. We have studied two samples of children with idiopathic
      generalized epilepsy from two different Italian populations. In both samples the
      haptoglobin *1/*1 genotype is much less represented in epileptic children than in
      controls. These observations suggest that subjects carrying the Hp*1/*1 genotype,
      that has the lowest molecular size and diffuses more readily in the interstitial
      cerebral fluid, are more protected against idiopathic generalized epilepsy than
      those with other haptoglobin genotypes.

PMID- 15490287
TI  - Dementia with Lewy bodies: no association of polymorphisms in the human synphilin
      gene.

PMID- 15490288
TI  - Seronegative rheumatoid arthritis and gout.

PMID- 15490289
TI  - Song copying by humpback whales: themes and variations.
AB  - Male humpback whales (Megaptera novaeangliae) produce long, structured sequences
      of sound underwater, commonly called "songs." Humpbacks progressively modify
      their songs over time in ways that suggest that individuals are copying song
      elements that they hear being used by other singers. Little is known about the
      factors that determine how whales learn from their auditory experiences. Song
      learning in birds is better understood and appears to be constrained by stable
      core attributes such as species-specific sound repertoires and song syntax. To
      clarify whether similar constraints exist for song learning by humpbacks, we
      analyzed changes over 14 years in the sounds used by humpback whales singing in
      Hawaiian waters. We found that although the properties of individual sounds
      within songs are quite variable over time, the overall distribution of certain
      acoustic features within the repertoire appears to be stable. In particular, our
      findings suggest that species-specific constraints on temporal features of song
      sounds determine song form, whereas spectral variability allows whales to
      flexibly adapt song elements.

PMID- 15490290
TI  - Copying results and copying actions in the process of social learning:
      chimpanzees (Pan troglodytes) and human children (Homo sapiens).
AB  - There is currently much debate about the nature of social learning in
      chimpanzees. The main question is whether they can copy others' actions, as
      opposed to reproducing the environmental effects of these actions using their own
      preexisting behavioral strategies. In the current study, chimpanzees (Pan
      troglodytes) and human children (Homo sapiens) were shown different
      demonstrations of how to open a tube-in both cases by a conspecific. In different
      experimental conditions, demonstrations consisted of (1) action only (the actions
      necessary to open the tube without actually opening it); (2) end state only (the
      open tube, without showing any actions); (3) both of these components (in a full
      demonstration); or (4) neither of these components (in a baseline condition). In
      the first three conditions subjects saw one of two different ways that the tube
      could open (break in middle; caps off ends). Subjects' behavior in each condition
      was assessed for how often they opened the tube, how often they opened it in the
      same location as the demonstrator, and how often they copied the demonstrator's
      actions or style of opening the tube. Whereas chimpanzees reproduced mainly the
      environmental results of the demonstrations (emulation), human children often
      reproduced the demonstrator's actions (imitation). Because the procedure used was
      similar in many ways to the procedure that Meltzoff (Dev Psych 31:1, 1995) used
      to study the understanding of others' unfulfilled intentions, the implications of
      these findings with regard to chimpanzees' understanding of others' intentions
      are also discussed.

PMID- 15490291
TI  - Do chickens (Gallus gallus f. domestica) decompose visual figures?
AB  - To investigate whether learning to discriminate between visual compound stimuli
      depends on decomposing them into constituting features, hens were first trained
      to discriminate four features (red, green, horizontal, vertical) from two
      dimensions (colour, line orientation). After acquisition, hens were trained with
      compound stimuli made up from these dimensions in two ways: a separable (line on
      a coloured background) stimulus and an integral one (coloured line). This
      compound training included a reversal of reinforcement of only one of the two
      dimensions (half-reversal). After having achieved the compound stimulus
      discrimination, a second dimensional training identical to the first was
      performed. Finally, in the second compound training the other dimension was
      reversed. Two major results were found: (1) an interaction between the dimension
      reversed and the type of compound stimulus: in compound training with colour
      reversal, separable compound stimuli were discriminated worse than integral
      compounds and vice versa in compound training with line orientation reversed. (2)
      Performance in the second compound training was worse than in the first one. The
      first result points to a similar mode of processing for separable and integral
      compounds, whereas the second result shows that the whole stimulus is
      psychologically superior to its constituting features. Experiment 2 repeated
      experiment 1 using line orientation stimuli of reversed line and background
      brightness. Nevertheless, the results were similar to experiment 1. Results are
      discussed in the framework of a configural exemplar theory of discrimination that
      assumes the representation of the whole stimulus situation combined with transfer
      based on a measure of overall similarity.

PMID- 15490292
TI  - Comments on use of a disk diffusion method with cefoxitin (30 microg) to detect
      methicillin-resistant Staphylococcus aureus.

PMID- 15490293
TI  - Identification and immunoreactivity of proteins released from Streptococcus
      agalactiae.
AB  - The aim of the present study was to identify released proteins of Streptococcus
      agalactiae and to investigate their immunoreactivity with human sera to determine
      whether such proteins might be viable as carrier proteins in conjugate vaccines.
      Infections with S. agalactiae are the leading cause of sepsis and meningitis in
      neonates. Vaccination of women of childbearing age would be a desirable
      alternative to intrapartum antibiotic prophylaxis, but factors that mediate S.
      agalactiae invasive disease and virulence are poorly defined. Capsule-based
      vaccines have shown only low immunogenicity to date, and interest has shifted
      towards S. agalactiae proteins, either as candidate vaccine antigens or as
      carrier proteins for serotype-specific S. agalactiae polysaccharides. In this
      study, some major released proteins of S. agalactiae could be identified,
      including molecules known to be present on the surface of bacterial cells but not
      previously described as released proteins, such as CAMP factor, a phosphocarrier
      protein, aldolase, enolase, PcsB, and heat-shock protein 70. Serotype-specific
      differences in the protein patterns of extracellular products and
      immunoreactivity with human sera could be detected by SDS-PAGE and Western blot.
      The identification of unexpected released proteins may indicate secondary
      functions for these proteins. In addition, the widespread immunoreactivity of
      these proteins with human sera as shown by Western blot indicates that released
      proteins may be promising candidates as carrier proteins in conjugate vaccines.

PMID- 15490294
TI  - Pharmacokinetics/pharmacodynamics of echinocandins.
AB  - The novel class of echinocandins represents a milestone in antifungal drug
      research that has further expanded our therapeutic options. The favorable
      pharmacokinetic profile of the echinocandins has been elucidated in animal and
      human studies. The echinocandins are targeted for once-daily dosing and are not
      metabolized through the cytochrome P450 enzyme system, and they are generally
      well tolerated due to lack of mechanism-based toxicity. Little is known, however,
      about the disposition of these compounds in tissues and body fluids and the
      relationships between dosage, concentrations in the body, and antifungal efficacy
      in vivo. Many unanswered questions remain, including the importance of the high
      protein binding and the concentrations of free antifungal agents at target sites.
      Although recent attempts have been made to ensure the reproducibility of in vitro
      tests, the clinical usefulness of these tests is still unreliable and their
      relevance remains controversial. In vitro activity must be correlated with
      achievable concentrations at the site of infection. As little is known about the
      relationship between the pharmacokinetics and the pharmacodynamics of the
      echinocandins, increased incorporation of these principles in experimental and
      clinical studies is an important objective that will benefit the treatment and
      prophylaxis of life-threatening invasive fungal infections in immunocompromised
      patients.

PMID- 15490295
TI  - High-coverage profiling analysis of genes expressed during rice seed development,
      using an improved amplified fragment length polymorphism technique.
AB  - A novel method, based on quantitative PCR and amplified fragment length
      polymorphism was applied to the analysis of high-coverage gene expression
      profiles during the development of rice seeds. This represents the first report
      of the application of this method to plants, which permitted the detection and
      analysis of approximately 70% of all the genes that are expressed in rice. The
      method was used to compare gene expression at different developmental stages,
      subspecies or cultivars, and phyletic lines to identify genes of interest through
      differences in their level of expression. Using this approach, even novel
      anonymous genes could be detected. Examples of these include the soluble starch
      synthase (SS) II-I and the rice branching enzyme 4 (rbe4) genes in the starch
      synthesis pathway. A profiling database was compiled and the results compared
      with public data on full-length cDNA sequences of rice. The method enables
      candidate novel genes to be immediately identified among the large numbers of
      genes that are expressed during the development of rice seeds. Our results will
      contribute to a better understanding of comparative transcriptomics in all plant
      species.

PMID- 15490298
TI  - Tobacco smoking and chronic destructive periodontal disease.
AB  - Tobacco smoking is the main risk factor associated with chronic destructive
      periodontal disease. No other known factor can match the strength of smoking in
      causing harm to the periodontium. The harmful effects manifest themselves by
      interfering with vascular and immunologic reactions, as well as by undermining
      the supportive functions of the periodontal tissues. The typical characteristic
      of smoking-associated periodontal disease is the destruction of the supporting
      tissues of the teeth, with the ensuing clinical symptoms of bone loss, attachment
      loss, pocket formation, and eventually tooth loss. A review of the international
      literature that has accumulated over the past 20 years offers convincing evidence
      that smokers exhibit greater bone loss and attachment loss, as well as more
      pronounced frequencies of periodontal pockets, than non-smokers do. In addition,
      tooth loss is more extensive in smokers. Smoking, thus, considerably increases
      the risk for destructive periodontal disease. Depending on the definition of
      disease and the exposure to smoking, the risk is 5- to 20-fold elevated for a
      smoker compared to a never-smoker. For a smoker exposed to heavy long-life
      smoking, the risk of attracting destructive periodontal disease is equivalent to
      that of attracting lung cancer. The outcome of periodontal treatment is less
      favorable or even unfavorable in smokers. Although long-term studies are rare,
      available studies unanimously agree that treatment failures and relapse of
      disease are predominantly seen in smokers. This contention is valid irrespective
      of treatment modality, suggesting that smoking will interfere with an expected
      normal outcome following commonplace periodontal therapies. The majority of
      available studies agree that the subgingival microflora of smokers and non
      smokers are no different given other conditions. As a consequence, the elevated
      morbidity in smokers does not depend on particular microflora. The mechanisms
      behind the destructive effects of smoking on the periodontal tissues, however,
      are not well understood. It has been speculated that interference with vascular
      and inflammatory phenomena may be one potential mechanism. Nicotine and carbon
      monoxide in tobacco smoke negatively influence wound healing. Smoking research
      over the past two decades has brought new knowledge into the domains of
      periodontology. Even more so, it has called into question the prevailing paradigm
      that the disease is primarily related to intraoral factors such as supra- and
      subgingival infection. Smoking research has revealed that environmental and
      lifestyle factors are involved in the onset and progression of the disease. Being
      the result of smoking, destructive periodontal disease shares a common feature
      with some 40 other diseases or disorders. As a consequence, periodontal disease
      should be regarded as a systemic disease in the same way as heart disease or lung
      disease. Thus, chronic destructive periodontal disease in smokers is initiated
      and driven by smoking. Its progression may or may not be amplified by unavoidable
      microbial colonization.

PMID- 15490296
TI  - Behavior of adhesive boundary lubricated surfaces under shear: effect of grafted
      diblock copolymers.
AB  - The shear behavior and the normal interaction between mica surfaces covered by
      surfactant or surfactant-polymer mixtures were studied with a Surface Forces
      Apparatus (SFA) nanotribometer. If the surfaces are compressed while fully
      immersed in an aqueous surfactant solution that adsorbs in the form of flat
      bilayers, hemifusion can be induced. When the hemifused surfaces are subject to
      shear, at least five different dynamic regimes can be recognized. The general
      behavior may be described by a model based on the kinetics of formation and
      rupture of adhesive bonds between the shearing surfaces, with an additional
      viscous term. Once the adsorbed surfactant layer is decorated with physigrafted
      copolymers, the number of sliding regimes may be reduced to only one, in which
      the shear stress increases sublinearly with the driving velocity. The adhesion
      energy and the resistance to hemifusion of the adsorbed surfactant-polymer layers
      are also strongly modified as the grafting density increases.

PMID- 15490299
TI  - Stimulation of guanylate cyclase in rat parotid membranes by phosphate.
AB  - The natriuretic peptide receptor guanylate cyclases are members of the membrane
      bound guanylate cyclase family. Atrial natriuretic pepticle (ANP) stimulates
      guanylate cyclase A, which is predominantly expressed in the rat parotid gland.
      ATP is well known to increase ANP-stimulated guanylate cyclase, with Mg2+ as a
      cofactor. We investigated the regulation of guanylate cyclase activity in rat
      parotid membranes with Mn2+ as a cofactor, because enzyme activity was much
      higher with Mn2+ than with Mg2+. ANP (10(-7)M) stimulated guanylate cyclase
      activity to 120%-130% of the control level, and ATP (0.1-1.0 mM) depressed its
      activity, with or without ANP, to 70%-80% of the control. Enzyme activity was
      increased by the addition of phosphate (5-20 mM). In the presence of phosphate (5
      mM), guanylate cyclase with and without ANP was maximally stimulated to 5- and
      6.6-fold of the control, respectively. The net stimulation of guanylate cyclase
      by ANP was increased at ATP concentrations between 0.2 and 0.5 mM in the presence
      of phosphate (5 mM or 10 mM), but no change was observed in the absence of
      phosphate. Phosphate not only stimulated guanylate cyclase in the absence of ATP
      but altered the ATP regulation of ANP-stimulated guanylate cyclase. The
      stimulation of guanylate cyclase by phosphate may depend on a peculiarity of rat
      parotid membranes.

PMID- 15490300
TI  - Radioprotection of the murine submandibular gland by isoproterenol:
      autoradiography study with 3H-leucine.
AB  - Irradiation of the salivary glands results in the generation of free radicals
      from metal ions present in the secretory granules of acinar cells, a process that
      is believed to exacerbate radiation damage to the salivary glands. We therefore
      conducted a comparative investigation of radiation damage to the acinar cells of
      murine submaxillary glands in which granule secretion had been induced, and used
      autoradiography to visualize the pathological changes. Male BALB/c mice, at 8
      weeks of age, were divided into four groups: a no-isoproterenol (IPR) and no
      irradiation group (group I), a no-IPR, irradiated group (group II), an IPR, no
      irradiation group (group III), and an IPR, irradiated group (group IV).
      Intraperitoneal injections of IPR were used, and 3 h later, the submaxillary
      region was irradiated with X-rays at a dose of 10 Gy. Three days after the
      irradiation, 3H-leucine was administered, and submaxillary glands were removed at
      predetermined times. Thin sections were prepared, and light- and electron
      microscope autoradiography was performed. The number of reduced silver particles
      per unit acinar cell area was determined by light-microscopic autoradiography,
      and the proportion of reduced silver particles in the rough endoplasmic
      reticulum, the Golgi apparatus, and secretion granules was determined by electron
      microscopic autoradiography. The result indicated that the effects of the
      radiation on the secretory potential of the submaxillary glands were diminished
      in acinar cells with a higher secretory granule content.

PMID- 15490301
TI  - Regulation of tenascin expression in cultured rat dental pulp cells.
AB  - Tenascin (TN) is a glycoprotein of extracellular matrix abundantly present in
      embryonic mesenchymal tissues. Transforming growth factor-beta1 (TGF-beta1),
      basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), hepatocyte
      growth factor (HGF), and retinoic acid (RA) are important regulators of
      dentinogenesis. Dental pulp cells have the capacity to differentiate into
      odontoblast-like cells. In this study, we investigated the effects of growth
      factors on TN expression and adhesive function using rat clonal dental pulp
      cells, RPC-C2A. Analyses of reverse transcription-polymerase chain reaction (RT
      PCR) and Western blotting revealed that RPC-C2A cells expressed TN molecules and
      that TGF-beta1, HGF, and RA increased expression of TN at the mRNA and protein
      level, while bFGF and EGF showed a weak effect. An adhesion assay revealed that
      treatment with TGF-beta1, HGF, and RA induced a marked reduction of cell
      attachment to fibronectin (FN)-coated surfaces, whereas there was no change with
      bFGF and EGF. Functional blocking of growth factor-stimulated TN protein by
      pretreating cells with anti-TN antibodies restored cell attachment to control
      levels. These findings suggest that TGF-beta1, HGF, and RA may regulate pulpal
      cell adhesion to FN-coated surfaces and that this effect is mediated by TN.

PMID- 15490302
TI  - Heat curing of UTMA-based hybrid resin: effects on the degree of conversion and
      cytotoxicity.
AB  - This study was designed to determine the effects of the heat curing time on a
      urethane tetramethacrylate (UTMA)-based hybrid resin and specifically on the
      degree of conversion (DC) and cytotoxicity. The materials used in this study were
      Estenia, a new-generation hybrid resin, and an experimental fiber reinforcement,
      Br-100. The DC values of the hybrid resin samples were measured using a Fourier
      transform infrared (FTIR) spectrophotometer after 180 s of light curing followed
      by heat curing (0, 15, 30, and 60 min). A method comparing intensities of C=C and
      N-H vibrations of the sample was used to calculate the final DC values. FTIR
      spectra were measured both inside and on the surface of the sample. The
      calculated DC values increased by increasing the heat curing times. After light
      curing only and after 15-min heat curing, the DC values inside the samples were
      smaller than the corresponding DC values at the surfaces of the samples. After 60
      min of heat curing, the samples achieved homogeneous polymerization (DC% = 65).
      The cytotoxicity of the material was studied from the glass fiber-reinforced
      hybrid resin samples, which were first light cured and then heat cured (15, 30,
      and 60 min). Cytotoxicity was tested using both direct contact and extract
      methods. For the extract tests, the test specimens were incubated in a cell
      culture media at 37 degrees , 54 degrees , or 72 degrees C for 24 h. The heat
      curing times used had no effect on cytotoxicity. The incubation temperature,
      however, did have a significant effect. The extract obtained from 72 degrees C
      incubation showed a cytotoxic effect whereas the others did not. The direct
      contact test did not show cytotoxicity.

PMID- 15490303
TI  - Lymphocyte changes in peripheral blood, spleen, and liver in DMBA-induced
      squamous cell carcinoma of mouse cheek skin.
AB  - The peripheral blood, spleen, and liver lymphocyte subsets of mice with
      experimental cheek skin carcinoma were determined. The carcinoma was induced by
      the topical application of 2% (w/v) 9,10-dimethyl-1,2-benzanthracene (DMBA) to
      cheek skin twice a week for 12 weeks, and it was examined macroscopically and
      histopathologically. The composition of lymphocyte subsets (T cells, B cells,
      CD4+ single-positive [SP] T cells, and CD8+SP T cells) in peripheral blood,
      spleen, and liver was determined by flow cytometry at 3-week intervals for up to
      24 weeks. Spleens and livers were assessed by determining their content of
      natural killer (NK)T cells. The results showed histopathological progression of
      the skin lesions from papilloma to squamous cell carcinoma at week 12. Body
      weight was significantly reduced from weeks 15 to 24, and spleen weight was
      significantly increased at weeks 21 and 24, but liver weight was not
      significantly different from the control. The lymphocyte subset composition of
      peripheral blood showed significant elevation of T cells at weeks 6 and 9,
      followed by reduced levels at weeks 21 and 24, with significant reduction of B
      cells at weeks 6 and 9, followed by elevation at weeks 21 and 24. CD4+SP T-cell
      content was elevated at weeks 6, 9, and 12, and reduced at weeks 21 and 24.
      CD8+SP T-cell content was significantly reduced at weeks 6, 9, and 12, and
      elevated at weeks 21 and 24. The composition of the lymphocyte subsets in the
      spleen was similar to their composition in peripheral blood. The composition of
      both T and B cells in the liver was significantly different from that in the
      corresponding control group, but no significant differences were found in either
      CD4+SP or CD8+SP T cells. These findings revealed that the DMBA-induced cheek
      skin carcinoma in mice affected not only the lymphocyte subsets in peripheral
      blood, but the cells in the spleen and liver as well.

PMID- 15490304
TI  - Large-scale investigation of genomic markers for severe periodontitis.
AB  - The purpose of the present study was to investigate the genomic markers for
      periodontitis, using large-scale single-nucleotide polymorphism (SNP) association
      studies comparing healthy volunteers and patients with periodontitis. Genomic DNA
      was obtained from 19 healthy volunteers and 22 patients with severe
      periodontitis, all of whom were Japanese. The subjects were genotyped at 637 SNPs
      in 244 genes on a large scale, using the TaqMan polymerase chain reaction (PCR)
      system. Statistically significant differences in allele and genotype frequencies
      were analyzed with Fisher's exact test. We found statistically significant
      differences (P < 0.01) between the healthy volunteers and patients with severe
      periodontitis in the following genes; gonadotropin-releasing hormone 1 (GNRH1),
      phosphatidylinositol 3-kinase regulatory 1 (PIK3R1), dipeptidylpeptidase 4
      (DPP4), fibrinogen-like 2 (FGL2), and calcitonin receptor (CALCR). These results
      suggest that SNPs in the GNRH1, PIK3R1, DPP4, FGL2, and CALCR genes are genomic
      markers for severe periodontitis. Our findings indicate the necessity of
      analyzing SNPs in genes on a large scale (i.e., genome-wide approach), to
      identify genomic markers for periodontitis.

PMID- 15490305
TI  - Association of advanced hypodontia and craniofacial morphology in Japanese
      orthodontic patients.
AB  - The purpose of this study was to examine the effects of advanced hypodontia on
      craniofacial morphology in Japanese patients. We defined advanced hypodontia as a
      congenital absence of four or more permanent teeth, excluding the third molars.
      Lateral cephalometric radiographs of 20 female orthodontic patients (age range,
      8.5 to 19 years; mean age, 13.9 years) were examined. Twenty-eight angular and 37
      linear measurements were taken from each cephalogram, and these cephalometric
      data were statistically analyzed and compared with the Japanese cephalometric
      standards. The most frequently missing teeth were the mandibular and maxillary
      second premolars, followed by the maxillary first premolars and the maxillary
      first molars, in that order. Compared with the Japanese standards, a smaller
      cranial base length and angle, a shorter maxillary length, a slightly prognathic
      and upward-rotated mandible, and retroclination of the upper and lower incisors
      were found in the patients studied. These craniofacial anomalies should be taken
      into consideration in treatment planning and mechanotherapy.

PMID- 15490306
TI  - Effects of sounds generated by a dental turbine and a stream on regional cerebral
      blood flow and cardiovascular responses.
AB  - Effects of sound generated by a dental turbine and a small stream (murmur) and
      the effects of no sound (null, control) on heart rate, systolic and diastolic
      blood pressure, and hemodynamic changes (oxygenated, deoxygenated, and total
      hemoglobin concentrations) in the frontal cortex were measured in 18 young
      volunteers. Questionnaires completed by the volunteers were also evaluated. Near
      infrared spectroscopy and the Finapres technique were employed to measure
      hemodynamic and vascular responses, respectively. The subjects assessed the
      murmur, null, and turbine sounds as "pleasant," "natural," and "unpleasant,"
      respectively. Blood pressures changed in response to the murmur, null, and
      turbine sound stimuli as expected: lower than the control level, unchanged, and
      higher than the control level, respectively. Mean blood pressure values tended to
      increase gradually over the recording time even during the null sound
      stimulation, possibly because of the recording environment. Oxygenated hemoglobin
      concentrations decreased drastically in response to the dental turbine sound,
      while deoxygenated hemoglobin concentrations remained unchanged and thus total
      hemoglobin concentrations decreased (due to the decreased oxygenated hemoglobin
      concentrations). Hemodynamic responses to the murmuring sound and the null sound
      were slight or unchanged, respectively. Surprisingly, heart rate measurements
      remained fairly stable in response to the stimulatory noises. In conclusion, we
      demonstrate here that sound generated by a dental turbine may affect cerebral
      blood flow and metabolism as well as autonomic responses.

PMID- 15490307
TI  - Three-dimensional analysis of dentist's eye movements.
AB  - We measured the eye movements of a dentist while a pediatric patient walked
      toward a dental chair. Bilateral eye movements were measured and analyzed three
      dimensionally based on the angle of convergence. The frequency of fixation points
      registered in each test ranged from 2 to 11, with an average of 6.6. No
      significant differences were observed when the experiments were grouped according
      to the age of the observed child. In 13 out of 74 experiments, the calculated
      distances between the observer and the fixation points corresponded to the actual
      distances. According to the patterns of where the fixation points occurred, 13
      experiments had an "inside-outside" pattern and 61 had an "outside-only" pattern.
      None of the experiments had an "inside-only" pattern. The "outside-only" group
      was further subclassified into 50 "behind-only" patterns, 5 "in front-only"
      patterns, and 6 "in-front-and-behind" patterns. As far as depth perception is
      concerned, the angle of convergence determined by the eye movements would rarely
      correspond to the actual distance between the observer and the fixation point.

PMID- 15490308
TI  - Mandibular lesions of vasoocclusive origin in sickle cell hemoglobinopathy.
AB  - Sickle cell hemoglobinopathy is an inherited disorder characterized by
      vasoocclusive crises. Involvement of the maxillofacial skeleton leading to
      radiopaque lesions that correspond to bone infarcts has rarely been reported in
      the literature. Forty-two adult patients suffering from sickle cell anemia were
      examined radiographically for radiopaque lesions situated in the course of a
      known vessel or in the apical region of the teeth. In 6 cases, such lesions were
      combined with facial pain during sickle cell crisis and absence of dental
      pathology and were considered to be of possible vasoocclusive origin. In
      conclusion, vasoocclusive involvement should be taken into consideration when
      assessing painful episodes or neurological symptoms in the maxillofacial region
      in this patient population.

PMID- 15490309
TI  - Immunocytochemical localization of mK1, a true tissue kallikrein, in the mouse
      parotid gland: sexual dimorphism and effects of castration and hypophysectomy.
AB  - In the normal parotid glands of mice at 12 weeks of age, mK1, a true tissue
      kallikrein, was detected at the apical rim of the striated ducts (SDs). Sexual
      dimorphism in the immunostaining intensity in parotid glands was seen, i.e.,
      immunostaining was more intense in males than in females. Under electron
      microscopy, secretory granules, being small in size, and condensed at the
      subluminal cytoplasm, were labeled with immunogold particles showing the presence
      of mK1. These secretory granules were rather abundant and large in males.
      Castration in males reduced the immunoreactivity of mK1 in the SD cells because
      of a decrease in the number and size of secretory granules as revealed by
      electron microscopy. Hypophysectomy in male mice resulted in considerable loss of
      immunoreactivity for mK1, which was characterized under electron microscopy by
      complete disappearance or significant reduction of secretory granules in many SD
      cells. These results suggest that mK1 expression in the SD cells of murine
      parotid glands is regulated by pituitary-dependent hormones, and sexual
      dimorphism of mK1 expression is regulated by androgens.

PMID- 15490310
TI  - Magnetic resonance imaging findings of nodular fasciitis in the mental region.
AB  - Nodular fasciitis (NF) is a benign reactive lesion of the soft tissues related to
      the fascia and characterized by fibroblastic proliferation. The most common site
      is the upper extremities (46%), followed by the head and neck region (20%). In
      the orofacial region, the lesion typically develops within the subcutaneous
      structures overlying the angle and inferior border of the mandible and the
      zygoma. Magnetic resonance imaging (MRI) findings of NF in the orofacial region
      are almost unreported in the literature. In the present case report, we describe
      MRI findings of mental NF in a 19-year-old woman. MRI revealed a well-defined,
      round soft-tissue mass lying on the mentum. On T1-weighted MRI, the lesion was
      isointense to skeletal muscle; it was hyperintense to skeletal muscle on T2
      weighted MRI, and was enhanced by Gd-diethylenetriamine pentaacetic acid (DTPA).
      Histologic examination revealed abundant myxoid degeneration dispersed in the
      lesion. The T2-weighted higher heterogeneous signal intensity was likely due to
      abundant myxoid degeneration or the cellular component of the lesion. A strong
      bright signal intensity belt appeared in the periphery of the lesion on Gd-DTPA
      enhancement. This rim enhancement appeared to represent small arterioles and
      venules that were visible in the peripheral area on histologic examination.

PMID- 15490312
TI  - Prenylated indole alkaloids from Flustra foliacea with subtype specific binding
      on NAChRs.
AB  - Several brominated indole alkaloids and a diterpene (1-7) were isolated from the
      dichloromethane extract of the North Sea Bryozoan Flustra foliacea. Alkaloid 4 is
      a new natural product, whose structure was elucidated by interpretation of
      spectroscopic data (NMR, mass, UV, and IR). All compounds were tested for their
      in vitro affinity towards the alpha4beta2* and alpha7* subtype of the neuronal
      nicotinic acetylcholine receptor (nAChR) using radioligand binding assays.
      Deformylflustrabromine (3) and deformylflustrabromine B (4) were shown to have
      affinities in the lower micromolar range for nAChRs, differing in their subtype
      preference.

PMID- 15490313
TI  - An ex-vivo angiogenesis assay as a screening method for natural compounds and
      herbal drug preparations.
AB  - Angiogenesis is a fundamental component of complex biological processes,
      including oncogenesis. The aim of this work was to optimise and validate an ex
      vivo angiogenesis assay as a quantitative (PC image) biological method for
      testing promising natural compounds and herbal drug preparations for their pro
      /anti-angiogenic activity. The bioassay is based on the principle of wound
      healing and quantifies the effect of angiogenic agents on neovessel outgrowth of
      human placental vessels embedded in a three-dimensional fibrin matrix. The assay
      was validated by using known, well characterised pro- and anti-angiogenic
      effectors (basic fibroblast growth factor and carboxyamidotriazole,
      respectively), and an angiogenesis inhibitor of plant origin (green tea leaves
      extract) was used as a reference product to demonstrate the applicability of the
      assay for plant extracts. Other standardised plant extracts prepared from olive
      tree leaves and horse chestnut seeds were tested for their angiogenic potential,
      but showed only slight inhibitory or no activity, respectively. The results
      presented here indicate that this human ex-vivo angiogenic assay is "ready to
      use" for screening of herbal drug preparations and pure compounds.

PMID- 15490314
TI  - Constituents of the seeds of Hernandia ovigera with inhibitory activity against
      cyclooxygenase-2.
AB  - A new dibenzylbutyrolactone lignan, (2 R,3 R)-5'-methoxyguayarol (1), was
      isolated from an EtOAc-soluble extract of the seeds of Hernandia ovigera using an
      in vitro activity-guided fractionation procedure based on the inhibition of
      cyclooxygenase-2. Also obtained were three known fatty acid derivatives, (S)
      coriolic acid, (+/-)-12,13-epoxyoleic acid, and (+/-)-glycerol 1-monolinolate,
      and seven known lignans, epiashantin, dehydrodesoxypodophyllotoxin,
      dehydropodophyllotoxin, (-)-hernolactone, (-)-pinoresinol, (-)-syringaresinol,
      and (-)-yatein. The structure, including absolute stereochemistry, of compound 1
      was determined using spectroscopic methods. All isolates were tested for their
      inhibitory effects against both cyclooxygenases-1 and -2, with (S)-coriolic acid
      and (+/-)-glycerol 1-monolinolate shown to have selective inhibitory activity
      with cyclooxygenase-2.

PMID- 15490315
TI  - Skin penetration studies of Arnica preparations and of their sesquiterpene
      lactones.
AB  - Alcoholic preparations of Arnica montana are widely used for the topical
      treatment of various inflammatory diseases. Sesquiterpene lactones (SLs) are
      mainly responsible for their anti-inflammatory activity. Here we have studied the
      penetration kinetics of Arnica tinctures prepared from dried Arnica flowers
      originating from different chemotypes as well as of their respective dominating
      SLs, helenalin isobutyrate and 11alpha,13-dihydrohelenalin acetate. Some
      alcoholic preparations of fresh Arnica flowers and an Arnica fresh plant gel were
      also included in the study. We used the stripping method with adhesive tape and
      pig skin as a model and determined the quantity of SLs in the stripped layers of
      the stratum corneum (SC). Thus, we observed the penetration into and permeation
      through this uppermost part of the skin. Whereas isolated SLs permeate through
      the SC only in a very small amount, permeation of SLs was much higher when they
      were present in the tinctures. Furthermore, differences of permeation were
      observed between helenalin and dihydrohelenalin derivatives. Permeation through
      the SC could be determined for the tested Arnica preparations of fresh Arnica
      flowers with two preparations showing the best penetration behaviour of all the
      tested substances. Moreover, the effects of incubation time as well as of
      repeated applications were investigated with one preparation. Altogether, this
      study shows that a sufficient amount of SLs might permeate the skin barrier by
      using Arnica preparations to exert anti-inflammatory effects and that the topical
      use of plant preparations may be advantageous compared to the isolated compounds.

PMID- 15490316
TI  - Inhibition of leukotriene biosynthesis by quinolone alkaloids from the fruits of
      Evodia rutaecarpa.
AB  - The n-hexane extract of the fruits of Evodia rutaecarpa showed a considerable
      inhibiting effect on leukotriene biosynthesis in human granulocytes. Bioassay
      guided fractionation of the extract led to the isolation of the 5 quinolone
      alkaloids: 1-methyl-2-nonyl-4(1H)-quinolinone, 1-methyl-2-(6Z)-6-undecenyl-4(1H)
      quinolinone, 1-methyl-2-(4Z,7Z)-4,7-tridecadienyl-4(1H)-quinolinone, evocarpine
      and 1-methyl-2-(6Z,9Z)-6,9-pentadecadienyl-4(1H)-quinolinone. The compounds
      exhibited inhibitory activity on leukotriene biosynthesis in a bioassay using
      human polymorphonuclear granulocytes, with IC50 values of 12.1, 10.0, 10.1, 14,6
      and 12.3 microM, respectively. Structure elucidation of the compounds was
      achieved by 1D and 2D NMR experiments and comparison of spectral data with
      literature data.

PMID- 15490317
TI  - HPLC-based activity profiling of Salvia miltiorrhiza for MAO A and iNOS
      inhibitory activities.
AB  - In the course of a screening of plant extracts for potential CNS and anti
      inflammatory activities, a dichloromethane extract of Salvia miltiorrhiza showed
      a pronounced inhibitory effect on recombinant monoamine oxidase A (MAO A) and on
      inducible NO synthase (iNOS) induction in Raw 267.4 cells. With the aid of HPLC
      based profiling techniques, activities could be linked, to a significant extent,
      to peaks of tanshinone-type diterpenoids, four of which were subsequently
      isolated. The IC50 of the most active compound, 15,16-dihydrotanshinone I, on
      human recombinant MAO A was at 23 microM, and 2.4 microM on lipopolysaccharide
      mediated iNOS induction in Raw 267.4 cells.

PMID- 15490318
TI  - Phenylpropanoid NF-kappaB inhibitors from Bupleurum fruticosum.
AB  - Two phenylpropanoids from Bupleurum fruticosum (Apiaceae/Umbelliferae) were shown
      to inhibit the transcriptional activity induced by PMA or TNFalpha of an NF
      kappaB-controlled reporter gene. Western blot experiments indicated that the
      phenylpropanoids did not prevent IkappaBalpha degradation, suggesting that their
      molecular target is at a post-IKB degradation level. Both compounds prevented
      cytokine (IL-1, IL-6, TNF, IL-8) release and prostaglandin E2 synthesis.

PMID- 15490319
TI  - Compounds from Epilobium angustifolium inhibit the specific metallopeptidases
      ACE, NEP and APN.
AB  - Willow herb (Epilobium angustifolium L.) extracts showed inhibitory activity
      against the metallopeptidases: neutral endopeptidase (NEP), angiotensin
      converting enzyme (ACE), and aminopeptidase N (APN). A bioassay-guided
      fractionation led to the isolation of several flavonoids and phenolic acids and
      an ellagitannin. The dimeric macrocyclic ellagitannin oenothein B inhibited the
      neutral endopeptidases in a dose-dependent manner with IC50 = 20 microM. Other
      polyphenols showed weaker activity but their synergistic activity cannot be
      excluded. Taking into account the role of these peptidases in prostate diseases,
      the results may partly support and explain the use of Epilobium extracts in folk
      medicine.

PMID- 15490320
TI  - Gene expression profiles of inducible nitric oxide synthase and cytokines in
      Leishmania major-infected macrophage-like RAW 264.7 cells treated with gallic
      acid.
AB  - The effects of gallic acid on the gene expressions of inducible nitric oxide
      synthase (iNOS) and the cytokines interleukin (IL)-1, IL-10, IL-12, IL-18, TNF
      alpha, and interferon (IFN)-gamma were investigated by reverse-transcription
      polymerase chain reaction (RT-PCR). The experiments were performed in parallel in
      non-infected and in L. major-infected RAW 264.7 cells and the expression profiles
      were compared with those mediated by IFN-gamma plus lipopolysaccharide (LPS). The
      infection per se induced the expression first of IL-1 and TNF-alpha mRNA, later
      that of IL-10 mRNA. Gallic acid induced low and transient levels of TNF-alpha and
      IL-10 in non-infected cells, and it clearly enhanced and prolonged iNOS and
      cytokine mRNA expressions in Leishmania-parasitised cells. Interestingly, and in
      contrast to activation by IFN-gamma/LPS, gallic acid also stimulated Leishmania
      infected cells to produce IFN-gamma mRNA. For IFN-alpha, a sandwich immunoassay
      was performed to determine its amount present in the supernatant of gallic acid
      stimulated RAW 264.7 cells. In showing predominant stimulation of infected cells
      and the induction especially of IFN-gamma, a cytokine that plays a central role
      in antimicrobial macrophage and T cell regulation, these data provide the basis
      for an immunological concept of gallic acid and possibly other plant polyphenols
      for their beneficial effects in various infectious conditions.

PMID- 15490321
TI  - Genetic profiling of Hypericum (St. John's Wort) species by nuclear ribosomal ITS
      sequence analysis.
AB  - A PCR-based DNA amplification method was applied to genetically distinguish the
      popular dietary supplement Hypericum perforatum L. (common St. John's Wort) from
      other related Hypericum species. Nuclear ribosomal gene sequences of the internal
      transcribed spacer (ITS) region were analyzed for 50 Hypericum taxa native to the
      Old and New Worlds, representing 11 of the 36 currently accepted taxonomic
      sections. This study provides a genetic method for authentication of commercial
      H. perforatum preparations. In addition, these data allow a preliminary
      assessment of phylogenetic relationships within the genus, revealing three
      strongly supported monophyletic clades, plus several secondary monophyletic
      groupings. Using ITS gene sequences, we were able to distinguish H. perforatum
      from all other species of Hypericum included in this study.

PMID- 15490322
TI  - Anatalline and other methyl jasmonate-inducible nicotine alkaloids from Nicotiana
      tabacum cv. By-2 cell cultures.
AB  - Anatalline [2,4-di(3-pyridyl)piperidine] accumulation was shown to be induced by
      methyl jasmonate in Nicotiana tabacum cv. BY-2 cell cultures. Beside anatabine,
      anatalline represented the most abundant alkaloid, moreover, it was always
      present in two isomeric forms occurring always in similar concentrations. Both
      isomers could be completely separated by GC-MS. For structural analysis, the
      isolation of both isomers was performed using a semi-preparative HPLC system. The
      structures of anatalline [cis-2,4-di(3-pyridyl)piperidine] and its stereoisomer
      trans-2,4-di(3-pyridyl)piperidine were confirmed by MS and 1D and 2D NMR spectral
      data. The biosynthetic origin of anatalline was studied by feeding alkaloid
      precursors to BY-2 cell cultures.

PMID- 15490323
TI  - Isolation and characterisation of a cysteine protease (phytolacain G), from
      Phytolacca americana roots.
AB  - Protein extracts obtained from dried and fresh roots of Phytolacca americana L.
      (Phytolaccaceae) were examined in order to identify and characterise individual
      proteins. The extracts were compared with a commercial pokeweed mitogen standard
      using SDS polyacrylamide gel electrophoresis (SDS-PAGE). A dominant protein,
      present in both the extracts and the pokeweed mitogen standard, was isolated by
      subsequent ammonium sulphate fractionation, anion exchange chromatography, gel
      filtration and SDS-PAGE. In this way it was purified 140-fold with about 20 %
      yield and 70-fold with about 13 % yield from dried and fresh roots, respectively.
      Its molecular mass as determined by gel filtration and SDS-PAGE was estimated to
      be about 25 kDa. Subsequent isoelectric focussing revealed one single protein
      band at pH 6.0. LysC digestion of the 25 kDa protein yielded several peptides
      which were subjected to micro-sequencing. Comparison with published sequences
      revealed that the protein isolated was phytolacain G, a cysteine protease
      previously isolated from unripe fruits of P. americana L. The enzyme showed a
      high affinity towards the oxidised insulin B-chain and was completely inhibited
      by trans-epoxysuccinyl- L-leucylamido(4-guanidino)-butane (E64). The purified
      phytolacain G showed "lectin-like" activities such as haemagglutination and
      mitogenic effects towards human lymphocytes.

PMID- 15490325
TI  - Cytotoxic saponins from Schefflera rotundifolia.
AB  - Eight new oleanane and lupane saponins (1-8) as well as two new benzyl glycosides
      (9 and 10) were isolated from the aerial parts of Schefflera rotundifolia (Ten)
      Frodin (Araliaceae) together with two known benzyl glycosides. Their structures
      were established using 1D- and 2D-NMR spectroscopy and mass spectrometry. The
      antiproliferative activity of all compounds was evaluated using three continuous
      murine and human culture cell lines J774.A1, HEK-293, and WEHI-164. Compounds 7
      and 8, having betulinic acid as aglycone, were the most active constituents.

PMID- 15490324
TI  - Nine new cytotoxic monotetrahydrofuranic Annonaceous acetogenins from Annona
      montana.
AB  - Nine monotetrahydrofuranic Annonaceous acetogenins, montalicins A-E (1-5), cis
      annoreticuin (6), montalicins F (7), I (8), and J (9), along with eight known
      acetogenins 10-17, were isolated from the seeds of Annona montana by a high
      performance liquid chromatographic (HPLC) method. The structures of all new
      isolates were elucidated and characterized by spectroscopic and chemical methods.
      These monotetrahydrofuranic Annonaceous acetogenins showed selectively potent
      cytotoxicity against two human cancer cell lines, 1A9 and Hep G2.

PMID- 15490326
TI  - New triterpene esters from flowerheads of Arnica lonchophylla.
AB  - From the flowerheads of Arnica lonchophylla Greene ssp. lonchophylla Maguire
      (Asteraceae), a variety of mono-, di- and trihydroxytriterpenes of the oleanane,
      ursane, lupane and dammarane types were isolated and their structures elucidated
      by EI and CI mass spectrometry and extensive NMR spectroscopic analysis. Most of
      the compounds are esterified at position 3 with lauric, myristic, palmitic and
      stearic acids. Several ester derivatives of known triterpenes represent new
      natural products. The triterpenetriols 20(30)-taraxasten-3beta,16beta,21alpha
      triol (arnitriol A) and lupane-3beta,16beta,20-triol, both isolated in the form
      of their C3-fatty acid ester derivatives, possess hydroxylation patterns which
      have not been described previously. Besides small amounts of triterpenetriol
      esters, the lauric, myristic, palmitic and stearic acid esters of arnidiol,
      faradiol, maniladiol and calenduladiol were also identified in the flowerheads of
      A. montana (Arnicae flos Ph. Eur.), A. chamissonis ssp. foliosa and A.
      angustifolia ssp. attenuata. A search for sesquiterpene lactones in the flowers
      of A. lonchophylla resulted in the identification of small amounts of helenalin
      and 11alpha,13-dihydrohelenalin.

PMID- 15490327
TI  - New constituents of Leontopodium alpinum and their in vitro leukotriene
      biosynthesis inhibitory activity.
AB  - Phytochemical investigations of the roots of Leontopodium alpinum Cass. resulted
      in the isolation and structure elucidation of six novel compounds and two known
      compounds. Novel constituents could be identified as the polyacetylenes 1-acetoxy
      3-angeloyloxy-(4 E,6 E)-tetradeca-4,6-diene-8,10,12-triyne and its (6 Z)-isomer,
      the kaurenic acid derivative methyl ent-7alpha,9alpha-dihydroxy-15beta-[(2 Z)-2
      methyl-but-2-enoyloxy]kaur-16-en-19-oate, the bisabolane derivative (1 R*,3 S*,4
      R*,6 S*)-9-(acetoxy)-4-hydroxy-1-[(2Z)-2-methylbut-2-enoyloxy]bisabol-10(11)-ene
      and the lignans [(2 S,3 R,4 R)-4-(3,4-dimethoxybenzyl)-2-(3,4,5-trimethoxyphenyl)
      tetrahydrofuran-3-yl]-methyl-(2 Z)-2-methylbut-2-enoate and its 3,4,5
      trimethoxybenzyl derivative. Known compounds, reported here for the first time
      for the genus Leontopodium, were identified as ent-kaur-16-en-19-oic acid and T
      cadinol. The obtained compounds were tested together with 15 previously described
      compounds of L. alpinum in an ex vivo leukotriene biosynthesis inhibition assay.
      The highest activities were determined for the bisabolane derivates (IC50: 7.7 to
      11.4 microM), one lignan (IC50: 10.7 microM) and the ent-kaurenoate (IC50: 10.4
      microM).

PMID- 15490328
TI  - Generation and characterisation of monoclonal antibodies to oleanolic acid.
AB  - Monoclonal antibodies to oleanolic acid, a pentacyclic triterpene, were generated
      using the hybridoma fusion method described by Kohler and Milstein . Protein
      conjugates of the target molecule for immunisation were prepared either by
      directly linking the isoprenoid to different protein carriers via the carboxylic
      function or after introduction of a succinic spacer between the protein carrier
      and position 3 of the target molecule. Antibodies of three different cell lines
      were further analysed by competitive ELISA and were shown to be directed either
      against both rings A and B or to ring E of the pentacyclic system. Thus these
      antibodies can be used in the specific detection of oleanolic acid itself or of a
      broad range of oleanolic acid derivatives sharing a specific structural moiety.
      Therefore these antibodies may be interesting tools for the screening of putative
      terpenoid-containing plants.

PMID- 15490329
TI  - Morphological, chemical and functional analysis of catuaba preparations.
AB  - Fourteen commercial samples of the popular Brazilian aphrodisiac Catuaba
      specified as bark drugs of Anemopaegma, Erythroxylum and Trichilia species were
      examined for identity and purity. Only a minority of the examined Catuaba samples
      contained the crude drugs claimed on the labels. More than half of the products
      were adulterated with different crude drugs. The majority of the samples
      contained a bark originating from Trichilia catigua. The TLC fingerprints
      confirmed the heterogeneity, in 50% of the samples tropane alkaloids of various
      concentrations were detected. TLC and HPLC methods for separation and
      identification of the tropane alkaloids were developed and their analytical data
      (RF values, retention times, ESI-MS) given. The structure elucidation of the two
      main alkaloids, catuabine D and its hydroxymethyl derivative, is presented. The
      1H- and 13C-NMR assignments of these alkaloids are discussed with regard to
      literature data. Neither aqueous nor methanolic extracts of the Trichilia catigua
      reference material nor alkaloid-enriched fractions of commercial samples showed
      any effect on the rabbit corpus cavernosum in an in vitro test.

PMID- 15490330
TI  - Cyclopentanoid cyanohydrin glucosides and amides of Lindackeria dentata.
AB  - A mixture of cyanogenic glucosides epivolkenin and taraktophyllin, 1,4-dihydroxy
      2-cyclopentenecarboxamide, and uridine were isolated from leaves of Lindackeria
      dentata (Flacourtiaceae). Another cyclopentanoid amide, (1 R,4 S,5 R)-1,4,5
      trihydroxy-2-cyclopentenecarboxamide, was synthesized in two steps from
      gynocardin, and shown to have the same relative configuration as a partially
      identified amide previously isolated from L. dentata bark.

PMID- 15490331
TI  - Red clover extracts stimulate differentiation of human osteoblastic osteosarcoma
      HOS58 cells.
AB  - Different extracts from red clover (Trifolium pratense L.) were tested for their
      ability to stimulate the activity of osteoblastic osteosarcoma cells (HOS58). As
      a key marker of osteoblasticity we chose the activity of alkaline phosphatase
      (ALP). Whereas butanol and methanol extracts had no influence on either ALP or
      cellular protein production, enzyme activity was increased significantly on
      incubation with chloroform extracts. All extracts were analysed for isoflavone
      content. The data clearly suggest a role for red clover isoflavonoids in the
      stimulation of osteoblastic cell activity.

PMID- 15490332
TI  - Inhibition of matrix metalloproteinase-2 and -9 activities by selected
      flavonoids.
AB  - Matrix metalloproteinases (MMPs) play an important role in physiological and
      pathological matrix degradation. Here, we report that flavonoids, at
      physiologically relevant concentrations, inhibit two members of this enzyme
      family, namely MMP-2 and -9. Eight flavonoids with increasing number of hydroxy
      groups and other modifications were compared for their capacity to inhibit
      recombinant catalytic domains of these proteases. EC50 values ranged from 59 and
      70 microM (primuletin/5-hydroxyflavone) to 9 and 4 microM (luteolin 7- O
      glucoside) for MMP-2 and -9, respectively. Interestingly, the latter glucoside
      was an equal (MMP-2) or even stronger (MMP-9) inhibitor than its aglycone,
      luteolin. For luteolin, one of the strongest flavonoids tested, kinetic analysis
      revealed a non-competitive type of inhibition. Our results add a novel function
      to the long list of biological effects of these ubiquitous plant constituents
      that may contribute to and enhance their modulating influence on extracellular
      matrix degradation and remodelling.

PMID- 15490333
TI  - Flavonoids of St. John's Wort reduce HPA axis function in the rat.
AB  - A common biological alteration in patients with major depression is the
      activation of the hypothalamic-pituitary-adrenal (HPA) axis, manifested as
      hypersecretion of adrenocorticotropic hormone (ACTH) and cortisol. The
      hyperactivity of the HPA axis in depressed patients can be corrected during
      clinically effective therapy with standard antidepressant drugs such as
      imipramine, indicating that the HPA axis may be an important target for
      antidepressant action. We previously showed that a methanolic extract of St.
      John's Wort (SJW) and hypericin, one of its active constituents, both have
      delayed effects on the expression of genes that are involved in the regulation of
      the hypothalamic-pituitary-adrenal (HPA) axis , whereas the phloroglucinol
      derivative hyperforin was inactive in the same model . Since flavonoids of SJW
      are also discussed as active constituents it was of interest to determine whether
      these compounds can modulate HPA axis function. Imipramine (15 mg/kg), hypericin
      (0.2 mg/kg), hyperoside (0.6 mg/kg), isoquercitrin (0.6 mg/kg) and miquelianin
      (0.6 mg/kg) given daily by gavage for two weeks significantly down-regulated
      circulating plasma levels of ACTH and corticosterone by 40 - 70 %. However, none
      of the compounds tested had an effect on plasma ACTH and corticosterone levels
      after chronic treatment (daily gavage for 8 weeks). Our data suggest that besides
      hypericin, flavonoids of SJW play an important role in the modulation of HPA axis
      function. Furthermore, the results support the hypothesis that flavonoids are
      involved in the antidepressant effects of SJW.

PMID- 15490334
TI  - Xanthones from Gentiana campestris as new acetylcholinesterase inhibitors.
AB  - In order to discover new acetylcholinesterase (AChE) inhibitors, different plant
      extracts were screened by a previously established TLC bioautographic method. The
      methanol extract of Gentiana campestris leaves exhibited significant inhibition
      of AChE activity. A bioactivity-guided fractionation approach was undertaken to
      isolate the active components. Four xanthones, bellidin, bellidifolin, bellidin 8
      O-beta-glucopyranoside (norswertianolin), and bellidifolin 8-O-beta
      glucopyranoside (swertianolin), were found to be responsible for the anti-AChE
      activity effects. Bellidifolin showed similar activity to galanthamine in this
      enzyme assay.

PMID- 15490336
TI  - [The situation in the year 1902].

PMID- 15490337
TI  - [How did the earth's oxygen atmosphere originate?].
AB  - The planet earth did not carry an oxygen atmosphere from the beginning. Though
      oxygen could arise from radiation mediated water splitting, these processes were
      not efficient enough to create a global gas atmosphere. Oxygen in the latter is a
      product of the photosynthetic activity of early green organisms. Only after
      biological mass-formation of oxygen the UV-protective ozone layer could develop,
      then enabeling life to move from water onto land. This took billions of years.
      The basics of the processes of biological oxygen liberation and utilization are
      described in the following as well as the importance of their steady state
      equilibrium. Also a hint is given to oxygen as a toxic compound though being a
      chemical prerequisite for aerobic life on earth.

PMID- 15490338
TI  - [Pulmonary gas exchange: classical and modern findings].
AB  - The functional anatomy of the pulmonary gas exchanger enables an adequate
      oxygenation even in extreme situations, e. g. high altitude. An important
      mechanism is the distribution of ventilation and pulmonary perfusion. With
      induction of anaesthesia a relevant ventilation-perfusion mismatch results in
      oxygenation impairment, which can be prevented by specific anaesthetic
      techniques.

PMID- 15490339
TI  - [Normoxia ?].
AB  - Under the aspect of tissue O (2)-supply anatomical and functional features within
      the range of the microcirculation are described. With regard to "Normoxia?" the
      term "critical pO (2)" is introduced, its functional role discussed and data from
      earlier studies are presented. Recent investigations on the dependence of the
      accumulation of HIF's (Hypoxia inducible factors) which increase tissue O (2)
      supply and lower O (2)-demand, have shown that HIF-accumulation increases steeply
      below a tissue pO (2) of 20 mm Hg, thus in a pO (2) range where earlier
      investigators determined their pO (2)(crit.) data. Apparently, the the pO
      (2)(crit.) of a tissue marks the boundary between Hypoxia and Normoxia. Under
      normoxic conditions O (2)-consumption is limited by tissue O (2)-demand, under
      hypoxic conditions consumption is limited by O (2)-supply.

PMID- 15490340
TI  - [Oxygen homeostasis in tissues and cells: how hypoxia regulates gene expression].
AB  - Every cell of the body is capable of measuring the environmental oxygen
      concentration. When oxygen supply falls below oxygen demand of the cell
      (hypoxia), a series of genes will be activated whose products help the cell, the
      tissue as well as the whole organism in adapting to these altered oxygen
      concentrations. The discovery of hypoxia-inducible transcription factors (HIFs)
      allowed the molecular understanding of these processes.

PMID- 15490341
TI  - [Performance of anesthesia systems in the future, O(2) delivery and O(2)
      measurement as example].
AB  - Closed loops will help to simplify the operation of anesthesia devices in the
      future. The technical prerequisites for the closed loop controlled delivery of
      oxygen are a electronically controlled dosage system, a fast and redundant O (2)
      measurement and the right algorithms. Benefits from this closed loop control are
      a steady quality of oxygenation, the O (2) uptake and consumption data.

PMID- 15490342
TI  - [100 years of Draeger Medical Technology (1902 - 2002) -- working for the
      applicability of oxygen].
AB  - This survey analyses the history of 100 years of Draeger Medical Technology.
      Between 1889 and 1902 a number of inventions on the field of pressure gas
      technology allowed to solve application problems, which until then proved major
      obstacles to the safe and efficient use of compressed gases such as oxygen,
      nitrous oxide or carbon dioxide for medical and industrial purposes. A special
      significance is to be awarded here to pressure reducing valves, but also reliable
      manometers, nozzles and valves for pressure tanks were not generally available
      until then. These were first successfully and on a really significant scale
      introduced into international medical and non-medical pressure-gas technology by
      Draeger Inc. (Luebeck/Germany), and proved particularly successful in anaesthesia
      and rescue-devices (e. g. in the "Roth-Draeger Anaesthesia Apparatus" (1902).
      Consequently, starting in 1902, Draeger Inc. increasingly put an emphasis on
      developing medical and rescue technology and -- by doing so -- gained an
      important influence on the history of the implementation of modern oxygen therapy
      and of inhalative anaesthesia. A survey of the historically most important
      Draeger-Developments is provided.

PMID- 15490343
TI  - [Oxcarbazepine in monotherapy in 324 patients with partial seizures (TRINOVA
      study)].
AB  - AIMS: The purpose of this study was to evaluate the effectiveness and
      tolerability of oxcarbazepine (OXC) administered as monotherapy in patients with
      partial seizures as a first therapeutic alternative or after the failure of other
      monotherapies. PATIENTS AND METHODS: A prospective, open, multicentre trial based
      on observation involving 324 patients between 6 and 87 years of age with partial
      seizures who had not received prior treatment with antiepileptic drugs (AED) (n =
      114) or in whom other monotherapies had failed (n = 210). These patients were
      administered OXC in the conditions usually found in clinical practice over a
      period of 52 weeks; effectiveness was evaluated by the reduction in the frequency
      of the seizures, tolerability was measured through the side effects related to
      the drug and quality of life was assessed by means of the changes reflected in
      the CAVE questionnaires, in the case of children, and the QOLIE-31 for adults.
      RESULTS: At the end of the study, total control over the seizures was 73.7% in
      patients who had not been treated previously and 43.8% in those in whom other
      monotherapies had failed; at the same time there was an improvement in the
      quality of life parameters. 42.9% reported side effects, which were usually
      tolerable or transient since they led to the withdrawal of OXC in only 9.6% of
      the patients. CONCLUSIONS: OXC is a very effective AED and is well tolerated as
      monotherapy in patients of all ages with partial seizures, either as the first
      choice therapy or as a substitution for other ineffective or poorly tolerated
      drugs.

PMID- 15490344
TI  - [Ambulatory neurological care in the Marina Baixa area, Alicante].
AB  - INTRODUCTION: The demand for neurological care depends on the type of population
      to be attended, among other variables. The Marina Baixa area, which includes
      towns such as Altea and Benidorm, has its own peculiar characteristics due to its
      being one of the places that is often chosen by pensioners from northern and
      central Spain and Europe to set up residence. AIM: The aim of this study was to
      determine the characteristics of the ambulatory neurological care in our health
      area. PATIENTS AND METHODS: Data on 1,000 patients attended in the Neurological
      Clinic at the Specialty Centre in Benidorm (age, sex, reason for visit, tests
      requested and destination on discharge) were recorded prospectively and
      consecutively. RESULTS: The mean age was 58.04 years (range 14-94) and 56.4% were
      females. 25% of the patients attended were over 75 years old. The main reasons
      for visiting were headache (28.2%) and cognitive impairment (21%). 26.5% were
      first-time visits, with a mean age of 55.02 years, which is significantly lower
      than that of the review patients (59.12 years; p = 0.003). 15.6% of the patients
      were discharged from hospital. A prolonged follow-up was foreseen for over 50% of
      them. The demand for care in 2003 was 27.5 per 1,000 inhabitants/year in the
      population above the age of 14 years. CONCLUSIONS: The higher the mean age of the
      population is, the greater the prevalence of neurodegenerative diseases will
      become and the more demand there will be for ambulatory care. Resources must be
      adjusted to this new situation and there is also a need to adopt the most
      suitable model of health care for chronic neurological patients.

PMID- 15490345
TI  - [Corticospinal dysfunction in patients with primary and amyotrophic lateral
      sclerosis].
AB  - INTRODUCTION: Corticoespinal dysfunction is a common finding in primary and
      amyotrophic lateral sclerosis (PLS and ALS). AIM. To compare the behaviour of
      motor evoked potentials (MEP) with transcranial magnetic stimulation (TMS) in
      patients with ALS and PLS. PATIENTS AND METHODS: It was performed a retrospective
      analysis of MEP recordings of 11 patients with PLS and 10 patients with sporadic
      ALS. Central motor conduction time and amplitude ratio were the selected
      variables for the statistical analysis of MEP from abductor pollicis brevis and
      tibialis anterior muscle from the four limbs, using non-parametric methods.
      RESULTS: As a general observation there was a high incidence of abnormal
      recordings in both groups of patients; in 30% of recording from ALS patients
      response to TMS was absent, but only the 4.5% in the group of PLS had the same
      characteristic. In PLS patients abnormal central motor conduction time was the
      most frequent finding, as it was the low amplitude ratio in ALS patients; both
      variables showed statistically significant differences between groups (Kruskall
      Wallis, H = 6.32, p = 0.011; and Kruskall-Wallis, H = 5.777, p = 0.0163,
      respectively). CONCLUSION: Corticoespinal dysfunction has different
      characteristics in ALS and PLS patients, and the analysis of MEP could add useful
      information for differential diagnosis of these diseases.

PMID- 15490346
TI  - [Mitochondrial encephalomyopathies and West's syndrome: a frequently
      underdiagnosed association].
AB  - INTRODUCTION: West's syndrome is known to have symptomatic, cryptogenetic and
      idiopathic forms. Greater knowledge of the different pathologies and the
      development of new diagnostic techniques have allowed the list of symptomatic
      forms to be extended and congenital disorders of the metabolism account for a
      significant percentage as an aetiopathogenic factor. Yet, although it is known
      that mitochondrial cytopathies can trigger the development of West's syndrome,
      few reports exist concerning their association. AIMS: Our aim in this paper is to
      report on four cases of West's syndrome in which a mitochondrial cytopathy was
      shown to be an aetiopathogenic factor. CASE REPORTS: Two females and two males
      aged between 2 and 10 months, who were suffering from West's syndrome.
      Biochemical and neuroimaging findings suggested a possible mitochondrial
      cytopathy, which was later confirmed in the four cases on observing a partial
      deficiency of some of the complexes of the mitochondrial respiratory chain in
      muscles; this was found to be simple in the first three (complexes III, I and IV,
      respectively) and combined in the fourth (complexes I and IV). CONCLUSIONS:
      Infantile spasms should be considered as one of the ways mitochondrial
      encephalomyopathies manifest themselves. As part of the process of diagnosing
      West's syndrome, we recommend tests be carried out to determine the levels of
      lactic and pyruvic acid, carnitine and amino acids in plasma, and possibly in the
      cerebrospinal fluid, as well as those of amino acids and organic acids in urine.
      A muscular biopsy must also be carried out in patients who are strongly suspected
      of having a mitochondrial cytopathy, as well as the corresponding molecular
      genetic study.

PMID- 15490347
TI  - [Opercular syndrome after bilateral cerebral surgery: presentation of a case
      report].
AB  - AIM: To present a case of bilateral opercular syndrome after surgery on both
      cerebral hemispheres. CASE REPORT: A girl was studied at 3 years of age because
      of a benign intracranial tumor in the middle region of the brain. At the age of 5
      years, the tumor was partially removed through the right hemisphere. Three years
      latter, the patient was operated through the left hemisphere because of growth in
      the tumor to the left side of the brain. After the second operation, the patient
      showed the complete symptomatology of the bilateral opercular syndrome, which did
      not change during this year. CONCLUSION: This is a case which the presence of a
      bilateral opercular syndrome seems to be caused by the surgical lesions of both
      opercular zones.

PMID- 15490348
TI  - [The mechanisms behind the generation of the slow oscillations found in EEG
      recordings during sleep].
AB  - INTRODUCTION: Electroencephalogram (EEG) recordings reflect different oscillatory
      activities during slow wave sleep (stages 2 and 3-4 of the sleep-waking cycle),
      namely d oscillations (< 4 Hz), sleep spindles and K complexes. These activities
      are essentially generated by the activity of the thalamo-cortical relay neurons,
      the neurons of the thalamic reticular nucleus and by the neurons in the cerebral
      cortex. DEVELOPMENT: The combination of the intrinsic electrophysiological
      properties of the thalamic and cortical neurons, together with their synaptic
      connections, are responsible for the generation of these oscillations. Extra or
      intracellular recordings of these neurons during spontaneous or anaesthetic
      induced sleep show how these neurons change their electrical activity during slow
      sleep due to the hyperpolarization of their membrane potential. Thus, the
      thalamic neurons lower their response to sensory stimuli and filter this
      information towards the cerebral cortex. Glial cells also contribute to the
      generation of the d waves seen in the EEG and oscillate synchronously with the
      cortical neurons. In addition, the oscillations of this neuronal and glial
      network is linked to important changes in the concentration of certain ions in
      the extracellular space; for instance, the K+ and Ca2+ concentration oscillates
      synchronously with the neuronal and the glial activity. CONCLUSIONS: The
      oscillations in the EEG, which are slower than those observed in the waking state
      or in paradoxical sleep, play a fundamental role in processing the information
      handled by the central nervous system and filter the irrelevant information
      towards the cerebral cortex.

PMID- 15490350
TI  - [The pathophysiological foundations of the psychiatric disorders in Parkinson's
      disease].
AB  - INTRODUCTION: In recent years, the non-motor symptoms of Parkinson's disease,
      including those of a psychiatric nature, have been receiving greater attention
      from the scientific community. DEVELOPMENT: In this paper we analyse the
      pathophysiological bases underlying the different psychiatric symptoms, examining
      the dopaminergic and non-dopaminergic mechanisms involved, as well as the
      importance of the extranigral disorders that are produced from the onset of the
      disease.

PMID- 15490351
TI  - [Neuropsychological disorders in Parkinson's disease: evaluating them and their
      impact on the caregiver].
AB  - INTRODUCTION: There are no specific scales for evaluating the broad profile of
      potentially relevant neuropsychological disorders associated to Parkinson's
      disease. Moreover, the information about their impact on the quality of life of
      caregivers (QLC) is scarce. OBJECTIVES: This study outlines a model of a
      practical questionnaire developed to evaluate the neuropsychological disorders in
      Parkinson's disease and how to apply it to determine the effect they have on the
      QLC. PATIENTS AND METHODS: A study was performed in two phases: 1. The
      application of a list of items from several scales used for neuropsychological
      disorders; 2. After selecting and reducing the number of items by means of
      psychometric methods, they were applied to a sample of patients. At the same
      time, using the data obtained from the above mentioned procedure, the impact of
      the neuropsychological disorders on the QLC was evaluated with the Glozman scale.
      RESULT: In Parkinson's disease some neuropsychological disorders are relatively
      frequent, unlike those observed in a control group (either because of their
      frequency or their intensity) and are significantly associated to other aspects
      of the disease. There was an overall deterioration of the QLC and this worsened
      significantly as PD progressed and the disability of the patient increased. With
      respect to the neuropsychological disorders, verbal communication (rS = -0.59),
      cognitive behavioural mental status (rS = -0.54) and depression (rS = -0.41) (p <
      0.001) were the domains significantly linked to deterioration of the QLC.
      CONCLUSIONS: The QLC of patients with Parkinson's disease is decreased and is
      correlated with the extent of the patient's motor disorders, functional status
      and neuropsychological disorders.

PMID- 15490352
TI  - [Psychiatric complications of Parkinson's disease: their symptoms and treatment].
AB  - INTRODUCTION AND DEVELOPMENT: Psychiatric symptoms in Parkinson's disease are
      relatively frequent, with a variation between 10 and 50%, according to different
      publications. They generally occur after several years of treatment. They may be
      symptoms derived from the disease itself or linked to the treatment used. These
      complications vary and include anxiety, affective and psychotic (hallucinations,
      delirium) disorders, as well as other alterations such as sexual, sleep and
      cognitive problems. CONCLUSIONS: Treatment must always be tailor-made to suit
      each individual and in many cases we have to resort to lowering or withdrawing
      the dopaminergic medication while, in others, treatment with benzodiazepines,
      antidepressants and atypical neuroleptic drugs is indicated.

PMID- 15490353
TI  - [Psychiatric symptoms of Parkinson's disease following deep brain stimulation
      surgery on the subthalamic nucleus].
AB  - AIM: To review the increasing number of papers that report diverse
      neuropsychiatric disorders that happen in patients diagnosed of Parkinson's
      disease submitted to brain deep stimulation of subthalamic nuclei with high
      frequency current. DEVELOPMENT: It is a fact the need to evaluate carefully all
      the patients who have to submit to this surgical procedure analyzing previous
      psychiatric history, and the possible appearance of psychiatric sphere symptoms
      after surgery. The acute depression and the euphoric moods (than can occur
      immediately after surgery) and major depression, obsession, widespread anxiety
      and substance abuse (among those of more delayed appearance) constitute examples
      of this pathology. The treatment of previous psychiatric disorders is forced in
      all cases and specially relevant in the major depression when suicide ideas
      coexist. CONCLUSIONS: Information that allow to predict the risk of developing
      depressive disorders in the postoperative period does not exist at present time,
      though it is more predictable that it happens in those patients with previous
      severe depressive history. In general, euphoric moods, apathy and depression,
      usually are transient and of multifactorial origin that includes the existence of
      endogenous predisposition, the change to an independence pattern after surgery,
      the psychotropic effect of levodopa, and the high frequency current stimulation
      effect on the non motor structures target and in the adjacent regions. It must be
      outlined that it is possible the appearance of psychotic symptoms after brain
      deep stimulation of subthalamic nuclei in patients with ideal results on motor
      disability.

PMID- 15490354
TI  - [Clozapine and olanzapine in the treatment of the psychotic disorders in
      Parkinson's disease].
AB  - AIMS: The most important and serious neuropsychiatric disorders in Parkinson's
      disease (PD) are the medication-induced psychoses. They are remarkably frequent
      and are linked to a dopaminergic over-stimulation caused by the drugs
      administered over a long period of time. This complication increases the
      morbidity and mortality rates in PD and in the past it was very difficult to
      treat. Yet, the atypical antipsychotics have transformed its prognosis.
      DEVELOPMENT: We review the general pharmacology of the atypical antipsychotics,
      in particular clozapine and olanzapine, which we have wide experience with. We
      present two series in which these drugs were used with the psychosis in PD. Our
      studies were performed using a strict prospective methodology, with scales that
      are valid for psychosis, and the patients' motor signs. Both atypical
      antipsychotics were seen to improve the positive and negative symptoms of the
      patients, giving rise to no or scarce improvement of the motor signs of PD. The
      side effects of the two drugs were not important. Our two series are compared
      with others from the literature, with similar results as regards the improvements
      in the psychoses and the absence or only slight deterioration of Parkinson's
      disease. CONCLUSIONS: The psychoses induced by medication in PD are frequent and
      severe. The appearance of the atypical antipsychotics has come as a true
      'revolution' in their treatment, owing to the good results obtained in the
      treatment of the psychoses and the scant deterioration of the motor signs of PD.

PMID- 15490355
TI  - [Quetiapine and ziprasidone in the treatment of the psychotic disorders in
      Parkinson's disease].
AB  - INTRODUCTION: As neurologists we often find it necessary to use antipsychotics in
      our clinical practice. They are not only used in the treatment of the behavioural
      disorders accompanying dementias, but also in the psychotic symptoms that
      frequently appear or complicate the clinical progress of our patients suffering
      from Parkinson. PATIENTS AND METHODS: Taking into account the numerous side
      effects of the typical antipsychotic drugs, we began a prospective study on the
      use of a new antipsychotic agent, quetiapine, in the treatment of 134 patients
      with Parkinson's disease who presented signs or symptoms of parkinsonian
      psychosis at some time during the course of their clinical progression; results
      were analysed at three and six months. At the same time, we review the efficacy
      of another antipsychotic agent, ziprasidone, which from the chemical point of
      view fulfils a profile that suits the needs of our patients. At the time of
      writing this paper we have recorded 43 cases of patients with Parkinson's disease
      and concomitant parkinsonian psychoses, which responded adequately to treatment
      without any kind of side effects. RESULTS: The administration of quetiapine in
      doses of 25-50 mg/day brought about an important improvement in the control over
      the signs of parkinsonian psychoses in our patients. The same occurred with the
      administration of 20-40 mg/day of ziprasidone. Both drugs were found to be
      extremely well tolerated and of great clinical value in the treatment of this
      clinical entity. CONCLUSIONS: Both quetiapine and ziprasidone are drugs that can
      be of great value in the treatment of parkinsonian psychoses. In addition to
      their high degree of clinical effectiveness, they also have a broad safety
      profile and no side effects.

PMID- 15490356
TI  - [A historical introduction to the neuropsychological model].
AB  - INTRODUCTION: In this work we outline the different approaches and doctrines that
      have been successively developed throughout the history of western medicine with
      the intention of offering an overall view of the matter. DEVELOPMENT: The author
      believes that the most important facts from a conceptual point of view are
      centred around F. Gall's notion of the cerebral localisation of the psychic
      functions; the development of the notion of nerve centres put forward by Fritsch
      and Hitzig, which was the foundation for the splendid work of D. Ferrier, the
      true father of scientific neuropsychology; the work of Klest, which gave rise to
      a new neogallism in the sense that it represented a real effort to locate the
      higher psychic functions; the fundamental work of J.H. Jackson, especially in
      relation to the subject we are studying, and his ideas about the levels of
      functioning and integration of the nervous system, which enabled later
      developments to be carried out, such as that of MacLean, whose concept of the
      limbic system is a core matter in this area. Other milestones were W.H. Hess's
      critique of the notion of nerve centre and that of function by A.R. Luria, which
      is necessary to be able to understand the modern-day neuropsychological models,
      and finally the development of the ideas about the specialisation of the nervous
      system.

PMID- 15490358
TI  - [Intracranial abscess secondary to chronic frontal sinusitis].

PMID- 15490360
TI  - [Tonic spasms as the initial symptom of multiple sclerosis].

PMID- 15490359
TI  - [Generalised clonic tonic seizures triggered by anaesthesia with propofol and
      sevoflurane].

PMID- 15490361
TI  - [Primary central nervous system lymphoma and Creutzfeldt-Jakob disease].

PMID- 15490363
TI  - [The efficacy of a formula for estimating premorbid intelligence in the Spanish
      population].

PMID- 15490364
TI  - [The thalamus and nociception in the head].

PMID- 15490365
TI  - [The Examination of Men's Wits by Juan Huarte de San Juan, and the dawn of the
      neurobiology of intelligence in the Spanish renaissance].

PMID- 15490367
TI  - Targeting Breast Cancer with Care. Proceedings of a meeting. Prague, Czech
      Republic, February 2004.

PMID- 15490369
TI  - Molecular approach to breast cancer treatment.
AB  - The tumor biology of the individual patients' disease is increasingly becoming an
      important factor to consider when choosing a treatment for breast cancer.
      Equally, there is now more emphasis on understanding the mechanisms of
      carcinogenesis and how these can be exploited when designing new therapeutic
      agents. Tumorigenesis in humans is a multistep process involving genetic
      alterations that drive the progressive transformation of normal cells into
      malignant types. Dysregulated processes involved in tumorigenesis, such as
      regulation of cell cycle progression, angiogenesis, and apoptosis provide
      rational targets for novel therapies. The family of human epidermal growth factor
      receptors (HER) is well characterized and its role in normal cell growth and
      tumorigenesis has been extensively researched. Trastuzumab (Herceptin; F.
      Hoffmann-La Roche, Basel, Switzerland), an anti-HER2 monoclonal antibody (MAb),
      was one of the first rationally developed and clinically available targeted
      agents, setting the precedent for providing specific therapy for HER-dysregulated
      cancer. This and other targeted agents show how research in tumor biology can be
      used to develop improved cancer therapies. Capecitabine (Xeloda; F. Hoffmann-La
      Roche) is an example of a rationally designed cytotoxic treatment. It is designed
      to generate 5-fluorouracil preferentially in tumor cells by exploiting the higher
      activity of the activating enzyme thymidine phosphorylase in tumors compared with
      healthy tissues. Tumor-specific activation has the potential to enhance efficacy
      and minimize toxicity. Proof of this principle is provided by clinical trial
      results showing that capecitabine is effective and has a favorable safety profile
      in the treatment of metastatic breast cancer. In summary, we are now at the stage
      where breast cancer treatment will be determined by tumor biology as well as
      patient characteristics. Improved molecular characterization and greater
      understanding of tumorigenesis will enable more individualized treatment.

PMID- 15490371
TI  - Optimizing the management of HER2-negative metastatic breast cancer with
      capecitabine (Xeloda).
AB  - Patients with metastatic breast cancer (MBC) require chemotherapy that improves
      outcomes without compromising quality of life. To achieve optimal outcomes with
      chemotherapy, treatment choices should be influenced by patient and disease
      characteristics, as well as patient preferences. Capecitabine (Xeloda; F.
      Hoffmann-La Roche, Basel, Switzerland) combined with docetaxel achieves
      significantly superior response rates, time to progression, and overall survival
      compared with single-agent docetaxel. With a manageable safety profile,
      capecitabine/docetaxel is a particularly appropriate option for younger, fitter
      patients with rapidly progressing disease and/or visceral metastases. In
      addition, studies show that dosing flexibility with capecitabine/docetaxel allows
      management of side effects without compromising efficacy. However, for older
      patients and those with comorbidities or more indolent disease, single-agent
      capecitabine may be more appropriate. Studies show that front-line capecitabine
      is a highly effective and well-tolerated alternative to standard intravenous
      treatments. The activity of capecitabine in the first-line treatment of MBC is
      underpinned by its consistently high activity in MBC. As an oral agent that
      causes minimal alopecia and myelosuppression, capecitabine has the potential to
      significantly improve patient quality of life and convenience. In summary, the
      treatment of MBC will always need to be individualized, but a large body of
      evidence indicates that capecitabine, whether alone or in combination, can be
      offered to women early in the disease course.

PMID- 15490370
TI  - Improving patient care through molecular diagnostics.
AB  - Traditional cancer diagnostic techniques include assessment of histologic
      appearance, identification of specific tumor subtypes, tumor grading, assessment
      of lymph node status, and presence of metastasis. These are useful for initial
      evaluation, but are limited in their ability to predict response to treatment
      and/or risk of experiencing adverse events to particular treatments. Recently,
      there has been considerable progress in molecular diagnostics in this area. Using
      molecular-based technologies, it is now possible to identify some patients with
      an inherited risk of developing breast cancer, and to more accurately assess the
      prognosis of those who already have developed the disease. Various techniques are
      also available or under investigation to help select patients who are most likely
      to respond to certain types of treatment. At present, this includes diagnostic
      tests to identify single tumor markers for which specific therapies are
      available, such as estrogen receptor and HER2. Diagnostic systems that allow
      simultaneous assessment of multiple markers, such as DNA microarrays and
      proteomics, are currently being validated. The use of these systems will allow
      further development of customized therapies directed toward the particular
      molecular defects in a given cancer.

PMID- 15490372
TI  - Optimizing treatment of HER2-positive metastatic breast cancer.
AB  - The primary goal of therapy for metastatic breast cancer is to improve the
      outcome for patients. Ideally, this should be achieved with minimal short-term
      side effects and without long-term irreversible toxicity. Trastuzumab (Herceptin;
      F. Hoffmann-La Roche, Basel, Switzerland) is proven to be efficacious in women
      with metastatic breast cancer who have HER2-positive disease. Data from pivotal
      clinical trials and postmarketing surveillance in women with metastatic breast
      cancer confirm that trastuzumab is also well tolerated with a low incidence of
      conventional chemotherapeutic side effects. Severe adverse events are confined to
      serious infusion-related reactions and cardiac issues, which are infrequent and
      readily managed. Patients at risk of these severe events can be identified before
      starting trastuzumab therapy. Ideally, treatment should also be convenient for
      the patient. This can be achieved through less frequent dosing. A 3-weekly
      trastuzumab schedule, with higher individual loading and maintenance doses than
      the conventional weekly schedule, has been investigated. This has similar
      efficacy, tolerability, and pharmacokinetics (exposure) to the weekly regimen,
      providing a convenient schedule.

PMID- 15490373
TI  - Maximizing clinical benefit with trastuzumab.
AB  - To optimize patient management in breast cancer a number of factors are
      considered, including hormone receptor and HER2 status. A feasible approach for
      women with less aggressive, estrogen receptor/HER2-positive metastatic breast
      cancer is to consider trastuzumab (Herceptin; F. Hoffmann-La Roche, Basel,
      Switzerland) combined with endocrine therapy. Randomized clinical trials are
      ongoing to assess the combination of trastuzumab with aromatase inhibitors. In
      patients with aggressive HER2-positive metastatic breast cancer,
      trastuzumab/chemotherapy combination regimens are warranted. When administered
      first line in combination with a taxane, trastuzumab improves all clinical
      outcome parameters, including survival, in such patients. Trastuzumab adds little
      to the toxicity profile of taxanes, and trastuzumab combination therapy is
      associated with improvements in quality of life when compared with chemotherapy
      alone. There is encouraging evidence of improved efficacy when trastuzumab is
      combined with other cytotoxic agents with proven single-agent activity in breast
      cancer, including capecitabine (Xeloda; F. Hoffmann-La Roche), gemcitabine, and
      vinorelbine. Trastuzumab is also being investigated as part of triplet drug
      regimens. Trastuzumab has good single-agent activity in first-line therapy. This
      is of relevance to women with HER2-positive disease who are not suitable for, or
      do not wish to receive, cytotoxic chemotherapy. The benefits noted with
      trastuzumab-containing regimens were documented in clinical trials where
      trastuzumab was given until disease progression. A further rationale exists to
      continue trastuzumab beyond progression. Data from retrospective reviews indicate
      that this strategy is feasible.

PMID- 15490374
TI  - Future options with capecitabine (Xeloda) in (neo)adjuvant treatment of breast
      cancer.
AB  - As an active and well-tolerated agent in the treatment of metastatic breast
      cancer, capecitabine (Xeloda, F. Hoffmann-La Roche, Basel, Switzerland) has the
      potential to confer significant clinical benefits in the primary treatment of
      breast cancer. The minimal myelosuppression and alopecia associated with
      capecitabine, together with its potential for synergistic activity with a range
      of other anticancer therapies, lend support to its use in combination regimens
      with other commonly used cytotoxic agents. Trials to date show that capecitabine
      combinations incorporating taxanes, vinorelbine, anthracyclines, and cisplatin
      are active and well tolerated in the metastatic setting. To more fully explore
      the clinical utility of capecitabine in early breast cancer, an extensive,
      worldwide phase II/III program is evaluating capecitabine as a component of
      adjuvant and neoadjuvant therapy. Results presented to date of the large adjuvant
      and neoadjuvant trials incorporating capecitabine are encouraging and suggest
      that women with breast cancer might benefit from the activity of capecitabine
      early in the disease course.

PMID- 15490375
TI  - Future options with trastuzumab for primary systemic and adjuvant therapy.
AB  - HER2 positivity can be detected early in breast cancer development and is
      associated with a poor outcome. Primary systemic therapy with trastuzumab
      (Herceptin; F. Hoffmann-La Roche, Basel, Switzerland) in combination with taxanes
      and other cytotoxic agents has been studied in phase II clinical trials in women
      with HER2-positive breast cancer. These combinations have achieved pathologic
      complete response rates of 12% to 42% and clinical complete response rates of 30%
      to 67%. These results compare favorably with those of primary systemic therapy
      using standard combinations in patients with unselected (HER2-positive or 
      negative) breast cancer. Consequently, larger studies are in progress in which
      trastuzumab is administered before surgery in combination with chemotherapy.
      Trastuzumab is continued as monotherapy afterward to complete 1 year of treatment
      or until disease progression. These studies aim to provide further proof of the
      clinical benefits associated with trastuzumab as primary systemic therapy. They
      will also investigate the molecular determinants of sensitivity and resistance.
      In addition, four major randomized trials, in more than 13,500 patients, are
      investigating the impact of adding trastuzumab to standard adjuvant therapy.
      Planned interim cardiac safety analyses have been passed without concerns.
      Recruitment to these studies has either recently been completed or continues as
      planned. Together, this extensive program, which includes analysis of predictive
      molecular and pathologic makers, will establish the efficacy, safety, and role of
      trastuzumab in early breast cancer.

PMID- 15490377
TI  - Bisphosphonates in the treatment of skeletal metastases.
AB  - Metastatic bone disease puts an enormous burden on patients and health care
      resources. Disruption of normal bone homeostasis by bone metastases leads to
      troublesome skeletal complications, such as bone pain, pathologic fractures,
      hypercalcemia of malignancy, and spinal cord compression. Bisphosphonates are an
      effective treatment for skeletal complications. These agents act primarily by
      initiating biochemical processes that ultimately result in apoptosis of
      osteoclasts, but they also have a number of other antitumor functions (eg,
      inhibition of angiogenesis). At present, the most widely used bisphosphonates are
      oral clodronate and intravenous pamidronate and zoledronic acid. Although these
      agents are effective in reducing skeletal complications, they are associated with
      varying safety and convenience issues. More recently, the availability of
      ibandronate as intravenous and oral formulations represents a new alternative for
      the treatment of metastatic bone disease. Further studies are necessary to
      establish the comparative benefits of bisphosphonates in metastatic bone disease.

PMID- 15490378
TI  - Ibandronate reduces skeletal morbidity in patients with breast cancer.
AB  - Three phase III studies have assessed the efficacy of intravenous (IV) and oral
      ibandronate over 96 weeks for metastatic bone disease in patients with breast
      cancer. The primary endpoint for each trial was the skeletal morbidity period
      rate, defined as the number of 12-week periods with new bone complications,
      adjusted for the time spent on study. Both IV ibandronate 6 mg every 3 to 4 weeks
      and oral ibandronate 50 mg once daily significantly reduced the skeletal
      morbidity period rate compared with placebo ( P = .004 in each case). The studies
      were not powered to detect statistical significance on individual components of
      the skeletal morbidity period rate. Nevertheless, IV ibandronate significantly
      reduced vertebral fractures and the need for radiotherapy, while oral ibandronate
      led to significantly fewer bone events needing radiotherapy or surgery than
      placebo. Using a multivariate Poisson regression model, the mean reduction in the
      relative risk of new bone events compared with placebo was 40% with IV
      ibandronate 6 mg ( P = .0033), and 38% with oral ibandronate 50 mg ( P <.001).
      The clinical equivalence of IV and oral ibandronate was confirmed by a post-hoc
      Anderson-Gill analysis of time to multiple skeletal events. These results show
      that IV and oral ibandronate effectively reduce skeletal morbidity in breast
      cancer patients with bone metastases.

PMID- 15490379
TI  - Ibandronate in metastatic bone pain.
AB  - Bone pain is a frequent complication of metastatic bone disease, with severe
      consequences for patient mobility and quality of life. Bisphosphonates can reduce
      bone pain and augment palliative radiotherapy, although relief is often for a
      relatively short period of time. Ibandronate is the first bisphosphonate to
      provide sustained bone pain relief over 2 years and, unlike other
      bisphosphonates, has shown improvements in quality of life. In phase III studies
      of patients with bone disease from breast cancer, intravenous ibandronate 6 mg
      and oral ibandronate 50 mg reduced bone pain below baseline levels within 6
      weeks. Significant reductions were maintained throughout the 96-week study phase
      compared with placebo ( P < or =.001). Two open, nonrandomized studies examined
      the effect of intensive, high-dose intravenous ibandronate (4 mg on 4 consecutive
      days, or 6 mg on 3 consecutive days) in patients with breast cancer or other
      tumor types with opioid-resistant bone pain and in patients with urologic cancer.
      In each study, ibandronate rapidly relieved moderate-to-severe metastatic bone
      pain, improving quality of life and patient functioning. Both intravenous and
      oral ibandronate provide effective long-term relief from metastatic bone pain.
      This clinical benefit may reduce the burden of metastatic bone disease on health
      care resources by limiting the need for analgesics and radiotherapy to the bone.

PMID- 15490380
TI  - Profiling the safety and tolerability of bisphosphonates.
AB  - Because patients with metastatic bone disease suffer a significant burden from
      their illness and from anticancer treatments, it is therefore important to
      minimize the side effects of bisphosphonates. The intravenous bisphosphonates,
      zoledronic acid and pamidronate, have tolerability issues that include a flu-like
      syndrome, injection-site reactions, and occasional renal toxicity. Because of the
      potentially severe nature of the renal toxicity, renal monitoring is required
      before each dose, with drug withdrawal if the patients' renal function
      deteriorates. Oral clodronate often causes gastrointestinal disturbances,
      particularly diarrhea; compliance is often poor because of the large tablet size
      and multiple daily dosing. Long-term data have shown that the bisphosphonate
      ibandronate is well tolerated either intravenously or orally, with a renal safety
      profile similar to placebo and no evidence of cumulative renal damage. Studies
      investigating the effects of 15-minute infusions and intensive dosing indicate
      that intravenous ibandronate given rapidly or at high doses is also well
      tolerated with no renal safety concerns. Taken together, these results suggest
      that the favorable safety profile of ibandronate provides an important
      alternative to existing bisphosphonate options for metastatic bone disease. Using
      ibandronate could improve patient acceptability and simplify management, with
      reductions in the need for safety monitoring and management of adverse events.

PMID- 15490381
TI  - Patient management issues in metastatic bone disease.
AB  - The main goals of bisphosphonate therapy are to prevent and treat skeletal
      events, minimize disability, and relieve pain without increasing the overall
      burden that bone metastases (and their treatment) place on patients. The ease and
      convenience of treatment are important to patients, and there are data suggesting
      that patients prefer oral therapy over intravenous drugs to help them maintain a
      normal life. Intravenous therapy with zoledronic acid and pamidronate is
      currently time-consuming; preparation, renal monitoring, infusion, and follow-up
      use valuable health care resources. Intravenous ibandronate could help alleviate
      this burden because of its good renal safety profile. Although efficacious, oral
      clodronate has compliance problems because of multiple dosing, large tablet size,
      and gastrointestinal tolerability issues. Recent phase III trials of oral
      ibandronate have shown efficacy similar to that of intravenous ibandronate, with
      no compliance or tolerability concerns. Ibandronate appears to have several
      advantages over current therapies that could improve treatment acceptability and
      reduce the burden of disease on the health care system. Research continues into
      the efficacy, safety, and pharmacoeconomics of ibandronate.

PMID- 15490382
TI  - Managing metastatic bone disease: three case studies.
AB  - Metastatic bone disease constitutes a major clinical problem. Skeletal
      complications are common and lead to significant morbidity, and patients live
      with metastatic bone disease for several years, increasing the prevalence of this
      problem. Effective management aims to reduce the incidence of skeletal
      complications and relieve symptoms, such as severe bone pain, which adversely
      affect patient mobility and quality of life. This article describes and discusses
      strategies for managing metastatic bone disease, with particularly emphasis on
      the role of the bisphosphonate ibandronate. Two case histories show the long-term
      efficacy and tolerability of oral ibandronate in the treatment of metastatic
      breast cancer. The third case history illustrates the benefits of rapid pain
      relief from an intensive, high-dose regimen of intravenous ibandronate in
      metastatic prostate cancer.

PMID- 15490383
TI  - Perspectives on the future of bisphosphonate use in breast cancer patients.
AB  - Bisphosphonates are effective for reducing the skeletal complications of
      metastatic breast cancer. Current treatment guidelines tend to recommend starting
      bisphosphonates at the time of diagnosis of bone metastases and continuing
      indefinitely or until the patients' performance status declines substantially.
      While meta-analyses of clinical trials have suggested that treatment should
      continue for at least 6 months to reduce skeletal-related events, few data exist
      on alternative strategies to optimize therapy. Other indications for
      bisphosphonates in the management of breast cancer include managing reduced bone
      mineral density in patients with early stage disease. In addition, because of
      considerable preclinical and clinical evidence that they may have direct
      antitumor actions, bisphosphonates are being tested as adjuvant therapy for early
      stage breast cancer in a number of large clinical trials.

PMID- 15490384
TI  - 2003 annual report of the American Association of Poison Control Centers Toxic
      Exposure Surveillance System.

PMID- 15490385
TI  - Trauma: an annotated bibliography of the recent literature-2003.

PMID- 15490386
TI  - Acute intussusception 15 years postgastrectomy.

PMID- 15490387
TI  - Meningovascular syphilis and improvement with tissue-plasminogen activator (T
      PA).

PMID- 15490388
TI  - Sudden death after IV metoprolol administration in a patient with cardiomyopathy.

PMID- 15490389
TI  - Malignant ascites presenting as abdominal compartment syndrome.

PMID- 15490390
TI  - Spontaneous basilica vein rupture.

PMID- 15490391
TI  - Laryngeal edema and anaphalactic shock after topical propolis use for acute
      pharyngitis.

PMID- 15490392
TI  - Aortic intramural hematoma presenting as acute inferior wall MI with cardiogenic
      shock.

PMID- 15490393
TI  - Benzodiazepines versus NTG treatment of cocaine coronary syndromes.

PMID- 15490394
TI  - Pyopneumothorax after blunt trauma.

PMID- 15490395
TI  - An unusual presentation of renal infarction.

PMID- 15490396
TI  - Proceedings of the Third International Congress on Uremia Research. September 17
      20, 2003. Taormina-Messina, Italy.

PMID- 15490397
TI  - Factors for increased morbidity and mortality in uremia: hyperphosphatemia.
AB  - Hyperphosphatemia is a metabolic abnormality present in the majority of patients
      treated by dialysis. Inorganic phosphorus (iP) can be categorized as a true
      uremic toxin given its known in vivo and in vitro effects and the ability to
      reduce these effects by normalizing iP levels. However, despite regular and
      adequate dialysis treatment, the goal of normalization of phosphorus levels
      rarely is achieved. This article briefly evaluates the significance of
      hyperphosphatemia in hemodialysis patients, current therapeutic approaches, and
      describes a new model for evaluating the dialysis prescription for iP balance.

PMID- 15490398
TI  - Mechanisms of vascular calcification in uremia.
AB  - Vascular calcification and cardiovascular disease mortality are highly correlated
      with increased serum phosphate levels in end-stage renal disease patients.
      Mechanistic studies in cultured human smooth muscle cells (SMCs) indicate that
      increased phosphate levels induces both calcification and phenotypic transition
      through a pathway requiring a sodium-dependent phosphate cotransporter. Thus, in
      addition to contributing to increased calcium x phosphate product (Ca x P),
      hyperphosphatemia may have direct effects on SMCs that predispose these cells to
      calcium deposition in end-stage renal disease patients.

PMID- 15490399
TI  - Arterial calcification in chronic kidney disease.
AB  - Hyperphosphatemia is associated with soft-tissue calcification and bone disease.
      Nephrologists prescribe phosphate binders to decrease dietary phosphate
      absorption, reduce serum phosphorus concentrations, and minimize the risk for
      soft-tissue calcification and bone disease. Recent data suggest that the dose of
      calcium used as a phosphate binder may contribute to the risk for cardiovascular
      calcification. Chronic positive calcium balance from diet, dialysis, and calcium
      based phosphate binders or intermittent hypercalcemia may favor precipitation of
      calcium and phosphate into tissues. Calcium suppresses parathyroid hormone (PTH)
      secretion and bone turnover, limiting the ability of bone to incorporate calcium
      and phosphorus. Sevelamer, a non-absorbed polymer, allows physicians to bind
      dietary phosphate and decrease serum phosphorus without unwanted absorption of
      metals or calcium or over-suppression of PTH. In a comparative trial, calcium
      based phosphate binders were associated with progressive coronary artery and
      aortic calcification that was attenuated by sevelamer. The optimal phosphate
      binder is one that controls hyperphosphatemia prevents soft-tissue calcification
      and preserves bone health.

PMID- 15490400
TI  - C-reactive protein is a significant predictor of vascular calcification of both
      aorta and hand arteries.
AB  - Although evidence has accumulated indicating a close relationship between
      inflammation and atherosclerosis, the relationship between inflammation and
      vascular calcification in patients with chronic renal failure is unclear. In the
      present study, the relationship between C-reactive protein (CRP) and vascular
      calcification in dialysis patients was examined. Vascular calcification of the
      aorta and hand arteries of 512 hemodialysis patients without significant
      infection (age 58.8 +/- 10.1 y; 305 men, 207 women) were examined by
      roentgenography of the lateral abdomen and hands, respectively. Patients with a
      mean CRP level greater than 1.0 mg/L (n = 254) were older than those with a CRP
      level less than or equal to 1.0 mg/L (n = 258) and had a longer duration of
      dialysis, lower serum albumin level, and higher phosphate level ( P < .01, P <
      .05, P < .001, and P < .01, respectively). Prevalence of vascular calcification
      of aorta and hand arteries in the former group was significantly higher than in
      the latter (65.0% versus 43.8% for aorta, P < .0001; and 25.0% versus 14.7% for
      hand arteries, P < .01). In a multivariate logistic regression analysis adjusted
      for age, hemodialysis duration, sex, levels of calcium and phosphate, and
      presence of diabetes, CRP level was a significant predictor for the presence of
      aortic calcification (odds ratio for highest versus lowest quartile, 2.669; 95%
      confidence interval, 1.539-5.421, P = .0010) and of calcification of hand
      arteries (odds ratio, 2.243; 95% confidence interval, 1.039-4.841; P = .0395). In
      conclusion, the present study shows that increased levels of CRP are
      significantly associated with the presence of vascular calcification in both
      aorta and hand arteries (ie, with both atheromatous and medial forms of
      calcification), indicating evidence for a relationship between inflammation and
      vascular calcification in hemodialysis patients.

PMID- 15490401
TI  - Uremic vasculopathy.
AB  - Recent evidence suggests that uremic vascular calcification is an active cell
      mediated process resembling osteogenesis in bone rather than passive
      precipitation. We have identified increased expression of bone-associated
      proteins (osteopontin, bone sialoprotein, alkaline phosphatase, type I collagen),
      and the bone-specific transcription factor core-binding factor alpha-1 (Cbfa1) in
      histologic sections of inferior epigastric arteries obtained from patients with
      end-stage renal disease (ESRD) or calcific uremic arteriolopathy. In in vitro
      experiments, the addition of uremic serum to cultured vascular smooth muscle
      cells up-regulated osteopontin and Cbfa1 expression and accelerated
      mineralization. This implies that the uremic milieu may lead to dedifferentiation
      of vascular smooth muscle cells with subsequent mineralization. Further
      understanding of the pathophysiology of uremic vascular calcification is needed
      to design effective therapeutic strategies to intervene with this devastating
      condition in ESRD patients.

PMID- 15490402
TI  - Epidemiology and prevention of cardiovascular complication in chronic kidney
      disease patients.
AB  - The risk for cardiovascular disease is significantly higher among patients with
      chronic kidney disease (CKD) than among the general population, considering that
      cardiovascular disease is the prominent cause of both morbidity and mortality in
      dialysis patients. This is explained mainly by the considerable prevalence of
      cardiovascular risk factors among CKD patients since the earliest stages of renal
      impairment, which include not only the so-called traditional risk factors, but
      also a number of additional risk factors that are specific to CKD and to the
      dialytic treatment itself. Considering the multiplicity of cardiovascular risk
      factors operating in CKD patients, as well as the crucial impact of their
      cardiovascular condition on long-term outcome, it is mandatory that all the
      available interventions aimed at the correction of all the modifiable risk
      factors for cardiovascular disease are performed as early as possible in the
      progression of the disease. In particular, the results of several controlled
      clinical trials have shown that a timely correction of anemia and of calcium
      phosphate disorders leads to a significant improvement in the cardiovascular
      conditions of CKD patients. Evidence also is growing regarding the benefits of
      intervention of newly recognized risk factors for cardiovascular disease such as
      inflammation and oxidant stress.

PMID- 15490403
TI  - Roles of metabolic and endocrinological alterations in atherosclerosis and
      cardiovascular disease in renal failure: another form of metabolic syndrome.
AB  - Patients with end-stage renal disease have markedly increased risk for death from
      cardiovascular disease. Renal failure is associated with multiple metabolic and
      endocrinologic abnormalities, and these alterations are involved in advanced
      atherosclerosis and high cardiovascular risk. Increased insulin resistance index
      by homeostasis model assessment (HOMA-IR), a simple index of insulin resistance,
      was an independent predictor of cardiovascular mortality in nondiabetic patients
      on maintenance hemodialysis. Renal failure impairs lipoprotein metabolism leading
      to the atherogenic lipoprotein profile characterized by increased triglyceride
      rich remnant lipoproteins such as intermediate-density lipoprotein, an
      independent factor of increased aortic stiffness. Non-high-density lipoprotein
      cholesterol, the sum of cholesterol of intermediate-density lipoprotein and other
      apoB-containing lipoproteins, is an independent factor associated with increased
      arterial thickness and a predictor of cardiovascular death in hemodialysis
      patients. The risk for cardiovascular death in hemodialysis patients is
      associated closely with hypertension and malnutrition, but not with obesity. The
      constellation of insulin resistance, dyslipidemia, hypertension, and malnutrition
      in renal failure suggests the presence of another type of metabolic syndrome
      promoting cardiovascular disease. In addition, vitamin D deficiency and
      abnormalities in calcium, phosphate, and parathyroid hormone levels increase the
      death risk from cardiovascular disease in renal failure. It is expected that
      treatment of these metabolic and endocrinologic alterations would improve the
      survival of patients with renal failure.

PMID- 15490404
TI  - Hyperhomocysteinemia and cardiovascular disease in uremia: the newest evidence in
      epidemiology and mechanisms of action.
AB  - In the general population, hyperhomocysteinemia is an independent risk factor for
      cardiovascular disease (ischemic disease, such as stroke and myocardial
      infarction, and arterial and venous thrombosis). We can presume that the
      association is causal, based on the example of homocystinuria, and on the
      evidence put forward by several basic science and epidemiologic studies. However,
      the results of large intervention trials, which may grant further support to this
      hypothesis, are not yet available. In chronic renal failure and in uremia, the
      evidence that is offered by carefully performed prospective studies also indicate
      the presence of an association, although some studies suggest reverse
      epidemiology. The mechanisms underlying the association, and able to explain the
      several toxic effects of homocysteine, related or not to cardiovascular disease,
      are unclear. Oxidation, nitrosylation, and hypomethylation are among the
      postulated mechanisms. In uremia, protein hypomethylation interferes with protein
      repair; DNA hypomethylation impairs regulation of gene expression, whereas folate
      treatment reverts such alterations. Acylation, another structural modification
      able to impair protein function, is a possible mediator of homocysteine toxicity.

PMID- 15490405
TI  - Inflammation: cause of vascular disease and malnutrition in dialysis patients.
AB  - Inflammation occurs in response to tissue injury or the presence of foreign
      antigens and is important in the mobilization of specific immunologic and
      nonimmunologic defenses against injury. The vascular endothelium is altered to
      allow immune competent cells to access the interstitial space. Muscle and
      visceral proteins are catabolized and the amino acids are used either to supply
      energy or as substrates for the production of acute-phase proteins that play a
      role in defense. Restoration of muscle mass is impaired while inflammation is on
      going. Lipids are mobilized. Although serving a vital role in allowing host
      survival from acute injury or infection, if unimpeded, or if triggered
      inappropriately, the acute-phase response may instead lead to increased vascular
      injury and progressive loss of muscle and visceral protein pools causing
      malnutrition. Markers of inflammation (C reactive protein [CRP] or interleukin-6
      [IL-6] levels) are associated with cardiovascular risk in the general population
      and in dialysis patients. Hypoalbuminemia also is associated with cardiovascular
      risk in dialysis patients. Although albumin is considered a marker of nutrition,
      changes in albumin levels are associated with increased levels of acute-phase
      proteins. Persistent changes in albumin levels are caused by reduced albumin
      synthesis associated with inflammation and not decreased normalized protein
      catabolic rate. The cause(s) of inflammation must be identified and treated to
      resolve malnutrition and reduce cardiovascular risk.

PMID- 15490406
TI  - New cellular and molecular approaches for the treatment of cardiac disease.
AB  - Similar to the kidney in uremia, end-stage cardiac failure is an outcome common
      to many disparate disease processes including hypertension, various inflammatory
      pathologies, as well as ischemic loss of tissue. In regard to the heart, cellular
      and molecular mechanisms responsible for heart failure have been investigated
      with renewed intensity over the past several years with newer techniques of
      molecular genetics, genomic analysis, and cell biology. Although this article
      reviews some recent advances made in our understanding of molecular and cellular
      events in the heart leading to heart failure and explores possible new targets
      for therapeutics, the main point is to stress the importance of investigative
      interactions between organ physiologists and molecular and cellular biologists.
      These interactions between organ physiologists and molecular geneticists is
      stressed and supported as a mechanism for rapid advancement for both
      understanding the underlying pathophysiology of human disease and the development
      of therapeutic strategies.

PMID- 15490407
TI  - Chronic systemic inflammation in uremia: potential therapeutic approaches.
AB  - Systemic inflammation characterizes several chronic diseases including uremia.
      Inflammation may contribute to morbidity and mortality by enhancing protein
      calorie malnutrition, infectious complications, and atherosclerosis and
      cardiovascular disease. Although inflammation in renal disease can be caused, at
      least in part, by reduced renal clearance of proinflammatory mediators (tumor
      necrosis factor [TNF]-alpha, interleukin [IL]-6), several pathogenetic mechanisms
      are likely to contribute to direct activation of the inflammatory process under
      these conditions. These mechanisms include accumulation of advance glycoxidation
      end products, production of reactive oxygen species and oxidative damage, and
      chronic infection. Support for direct activation of systemic inflammation
      provides a strong rationale for use of anti-inflammatory treatments in uremia.
      The current article describes the association between uremia and inflammation,
      provides evidence for activation of inflammatory process, and provides potential
      therapeutic approaches.

PMID- 15490408
TI  - Management of calcium and bone abnormalities in hemodialysis patients.
AB  - In chronic renal failure, hyperphosphatemia, hypocalcemia, hyperparathyroidism,
      reduced activation of vitamin D, decreased level of calcium-sensing receptor,
      osteitis fibrosa, and osteomalacia are features related to calcium abnormalities.
      Hyperparathyroidism is a risk factor for survival of hemodialysis patients as
      well as hypoparathyroidism, which is another feature in hemodialysis patients.
      Treatment of these abnormalities includes control of parathyroid hormone (PTH)
      secretion, counteracting hyperphosphatemia, correction of hypocalcemia, and
      others. Various kinds of vitamin D analogs have been introduced recently in
      addition to calcitriol and alfacalcidol, which have a rather long history (eg,
      maxacalcitol and falecalcitriol). Sevelamer is a newly developed phosphate binder
      to treat soft-tissue calcification.

PMID- 15490409
TI  - Sagliker syndrome: uglifying human face appearance in late and severe secondary
      hyperparathyroidism in chronic renal failure.
AB  - Almost every patient with chronic renal failure (CRF) eventually develops
      secondary hyperparathyroidism (SH) unless they are treated with proper and novel
      medications in advanced medical centers by skilled medical personnel. Every kind
      of bone abnormality including skull deformities has been described in detail by
      almost every concerned researcher and textbook, but descriptions of this
      phenomenon are limited in the medical literature to the years from 1973 to 1977.
      To our knowledge, extensive data regarding uglifying human face appearances have
      not been defined so far in the literature. We are therefore making this addition
      to the clinical nephrology field by accumulating such data. After we found 2
      consecutive peculiar and unique patients with uglifying human face appearances in
      2000, we attempted to inform and draw attention to this new entity to all
      hemodialysis (HD) centers in Turkey, as well as in other developing countries
      around the world to collect data on this phenomenon. Accordingly, we visited
      dialysis centers and patients' houses to collect detailed information, including
      medical clinical histories, physical examinations, laboratory data, biographies,
      current medications, and so forth. We found 25 patients who had CRF, SH, short
      stature, extremely severe skull changes, maxillary and mandibular bone changes,
      teeth/dental abnormalities, and soft and innocuous tumoral tissues in the mouth
      (hence, uglifying the appearance of the face), fingertip changes, severe
      psychologic problems, and depression. It appears that patients with CRF may have
      a new syndrome of bone deformities that have long been neglected, ignored, and
      forgotten since the mid-1970s when they were first described. This is vital and
      critical information for the clinical status of patients who suffered from the
      syndrome that we have named Sagliker syndrome (SS), and we believe there are many
      more patients in the world who are suffering from it.

PMID- 15490410
TI  - Vitamin D analogs: actions and role in the treatment of secondary
      hyperparathyroidism.
AB  - Although calcitriol has been shown to have an important role in the pathogenesis
      of hyperparathyroidism, its use as a therapeutic agent often has been limited by
      calcemic and phosphatemic toxicity. Vitamin D analogs and the synthetic
      prohormones, with the potential to have lesser effects on calcium and phosphorus,
      have been introduced and shown to be effective therapeutic agents. Paricalcitol
      is used widely in the United States and may be associated with improved clinical
      outcomes. Further studies on the effects of these vitamin D sterols on the
      skeleton and further studies of potential differential effects on calcification
      processes will be forthcoming, and as the mechanisms of their lesser toxicity
      become understood, perhaps this will pave the way for a future generation of
      vitamin D analogs with even greater specificity for the suppression of
      hyperparathyroidism with lesser toxicity.

PMID- 15490411
TI  - Calcimimetic agents for the treatment of secondary hyperparathyroidism.
AB  - Calcimimetic agents function as allosteric activators of the calcium-sensing
      receptor (CaSR). In parathyroid tissue, they decrease the threshold for CaSR
      activation by extracellular calcium ions and diminish parathyroid hormone (PTH)
      secretion directly. Results from small clinical studies in hemodialysis patients
      with secondary hyperparathyroidism have shown that single oral doses of
      calcimimetic compounds abruptly decrease plasma PTH levels within 1 to 2 hours in
      a dose-dependent manner. Sustained decreases in plasma PTH levels can be achieved
      when daily oral doses are given for as long as 18 weeks. Decreases in plasma PTH
      levels often are associated with modest decreases in serum calcium and phosphorus
      levels, but symptomatic hypocalcemia is uncommon. Data gathered during larger
      more recent clinical trials lasting 12 to 24 months again indicate that plasma
      PTH levels can be decreased effectively with persistent and favorable decreases
      in serum phosphorus levels and in values for the calcium-phosphorus ion product
      in serum. Calcimimetic agents thus offer a novel treatment for secondary
      hyperparathyroidism in patients with chronic kidney disease stage 5, who are
      managed with dialysis. Unlike the vitamin D sterols, calcimimetic compounds
      effectively decrease plasma PTH levels without aggravating disturbances in
      mineral metabolism that have been associated with adverse clinical outcomes.

PMID- 15490412
TI  - Carnitine system in uremic patients: molecular and clinical aspects.
AB  - Carnitine is a small water-soluble molecule that is present in almost all animal
      species. It plays an indispensable role in fatty acid metabolism, where it is
      involved in the transport of activated fatty acids between different cellular
      compartments. Uremic patients, as well as patients with chronic renal failure,
      appear to have abnormal renal handling of carnitine leading to dyslipidemia,
      lethargy, muscular weakness, hypotension, cardiac dysfunction and arrhythmias,
      and recurrent cramps. It often is difficult to distinguish these symptoms from
      similar ones related to uremia and dialysis. Many investigators have advocated L
      carnitine supplementation in an attempt to alleviate carnitine deficiencies, and
      good results from this therapy have been reported. Moreover, several studies have
      shown that L-carnitine supplementation improves the response to erythropoietin.
      Chronic inflammation is another particular aspect affecting these patients. Anti
      inflammatory properties of L-carnitine in hemodialysis patients have been shown
      by our group. Treatment with L-carnitine (20 mg/kg, given intravenously at the
      end of each dialysis session for 6 mo), significantly decreased serum C-reactive
      protein (CRP) levels, a proinflammatory cytokine known to inhibit erythropoiesis.
      Moreover, data from published literature are indicative of L-carnitine modulation
      of the immune system by the activation of glucocorticoid receptors and the
      modulation of the transcription of glucocorticoid-responsive genes. Our study
      showed that in these patients, treatment with L-carnitine has been able to
      improve their body mass index, likely by promoting a positive protein balance.
      This aspect is strictly correlated with the status of insulin resistance, which
      is well described in patients with renal diseases. Many studies showed that
      carnitine allowed mitochondrial fatty acid usage to link to the rate of glucose
      usage, thus improving insulin resistance. In conclusion, clinical beneficial
      effects of L-carnitine treatment on patients suffering from renal diseases are
      supported by molecular evidence involving both inflammatory and metabolic aspects
      of the disease.

PMID- 15490413
TI  - Oxidative stress in uremia: nature, mechanisms, and potential consequences.
AB  - Oxidative stress has emerged as a constant feature of chronic renal failure
      (CRF). The presence of oxidative stress in CRF is evidenced by an overabundance
      of lipid, carbohydrate, and protein oxidation products in the plasma and tissues
      of uremic patients and animals. We recently have shown that oxidative stress in
      CRF animals is associated with and, in part, owing to up-regulation of superoxide
      producing enzyme, nicotinamide-adenine dinucleotide phosphate (NAD(P)H) oxidase,
      and down-regulation of superoxide dismutase (SOD). The functional significance of
      these findings was confirmed by favorable response to administration of the cell
      permeable SOD-mimetic agent, tempol, in CRF rats. Oxidative stress in CRF plays
      an important role in the pathogenesis of the associated hypertension (oxidation
      of NO and arachidonic acid and vascular remodeling), cardiovascular disease
      (oxidation of lipoproteins, atherogenesis), neurologic disorders (nitration of
      brain proteins, oxidation of myelin), anemia (reduction of erythrocyte lifespan),
      inflammation (nuclear factor kappa B activation), fibrosis, apoptosis, and
      accelerated aging. The CRF-induced oxidative stress is aggravated by diabetes,
      uncontrolled hypertension, and autoimmune diseases, which independently increase
      production of reactive oxygen intermediates, and frequently are associated with
      CRF. In addition, dialysis treatment (blood interaction with dialyzer membrane
      and dialysate impurities), acute and chronic infections (blood access infection,
      hepatitis, and so forth), and excessive parenteral iron administration intensify
      CRF-associated oxidative stress and its adverse consequences in patients with end
      stage renal disease. The problem is compounded by limited intake of fresh fruits
      and vegetables (K(+) restriction), which contain numerous natural phytochemicals
      and antioxidant vitamins.

PMID- 15490414
TI  - Genomic damage in end-stage renal failure: potential involvement of advanced
      glycation end products and carbonyl stress.
AB  - In patients with chronic renal failure, genomic damage has been shown by numerous
      biomarkers, such as micronuclei frequency and comet assay (single-cell gel
      electrophoresis) in peripheral lymphocytes, 8-hydroxy 2'-deoxyguanosine (8-OH-dG)
      content in leukocytes, mitochondrial DNA deletions in skeletal muscle tissue and
      hair follicles, as well as in DNA repair mechanisms in freshly isolated
      lymphocytes after ultraviolet light exposure. In the pathogenesis of DNA damage-
      besides genetic influences, enhanced reactive oxygen species (ROS), and lipid
      peroxidation-the genotoxic potential of advanced glycation end products (AGEs)
      and reactive carbonyl compounds deserve special attention. In fact, reactions of
      glucose with DNA can lead to mutagenic DNA AGEs. In vitro, incubation of tubulus
      cells with various AGEs and methylglyoxal induces DNA damage, which is suppressed
      by antioxidants. This underlines the role played by oxidative stress in DNA
      damage.

PMID- 15490416
TI  - Cellular mechanisms causing loss of muscle mass in kidney disease.
AB  - In stable adults or patients with kidney disease, the daily turnover of cellular
      proteins is very large, amounting to the quantity of protein in 1 to 1.5 kg of
      muscle. Consequently, even a small but persistent increase in protein degradation
      or decrease in protein synthesis leads to a substantial loss of muscle mass. In
      chronic kidney disease, the pathway that degrades muscle protein is the ubiquitin
      proteasome system. We tested whether either of two complications of chronic
      kidney disease, metabolic acidosis or insulin resistance accelerates the loss of
      muscle protein. Metabolic acidosis activates the ubiquitin-proteasome system and
      this can explain an large number of clinical conditions in which metabolic
      acidosis also causes loss of muscle protein. Insulin deficiency as a model of
      insulin resistance also activates the ubiquitin-proteasome system. Both
      complications also activate caspase-3 and we found that this protease performs a
      critical initial step in breaking down the complex structure of muscle to provide
      actin, myosin and fragments of these proteins as substrates for the ubiquitin
      proteasome system. Defects in insulin signalling processes can activate both
      caspase-3 and the ubiquitin-proteasome system to degrade muscle protein.
      Understanding mechanisms that activate protein breakdown will lead to therapies
      that successfully prevent the loss of muscle mass in patients with kidney
      disease.

PMID- 15490415
TI  - Disturbances of purine nucleotide metabolism in uremia.
AB  - The increased concentration of adenosine triphosphate (ATP) in erythrocytes from
      patients with chronic renal failure (CRF) has been observed in many studies but
      the mechanism leading to these abnormalities still is controversial. It is
      believed that hyperphosphatemia and metabolic acidosis triggering enhanced
      reutilization of purine bases are the factors responsible for changes in
      erythrocyte nucleotide concentration. During the past decade we have performed
      several studies. A summary of the obtained results is presented. A high
      performance liquid chromatography technique was used for the determination of
      plasma and intraerythrocyte nucleotide concentrations. Labeled adenine and
      adenosine were used for measuring adenine incorporation. In CRF patients treated
      conservatively increased concentrations of ATP levels and other nucleotides such
      as adenosine diphosphate were found. Adenosine monophosphate and hypoxanthine
      levels were lower than in controls. In hemodialyzed patients both ATP and
      adenosine monophosphate intraerythrocyte concentrations were higher than in
      controls. At the same time, adenosine monophosphate and hypoxantine level were
      comparable with levels in healthy people. The main pattern of nucleotides during
      hemodialysis remained unchanged, independent from the mode of therapy. The only
      exception was a decreased level of hypoxantine. Results of a consecutive study
      have suggested that the increased rate of adenine incorporation into the adenine
      nucleotide pool could be partially responsible for the increased ATP
      concentration in uremic erythrocytes. Last but not least, trying to elucidate the
      pathomechanism of adenine nucleotide disturbances in uremia, we have found that
      the concentration of N-methyl-2-pyridone-5-carboxamide (2PY), one of the end
      products of nicotinamide-adenine dinucleotide degradation, were enhanced in CRF
      patients to values that are potentially toxic. Our findings suggest that 2PY
      could be a novel uremic toxin. Disturbances of nucleotide metabolism are one of
      the important components of uremic syndrome.

PMID- 15490417
TI  - Ultrastructural changes of corpora cavernosa in men with erectile dysfunction and
      chronic renal failure.
AB  - Erectile dysfunction (ED) is a common and often distressing side effect of renal
      failure. Uremic men of different ages report a high variety of sexual problems,
      including sexual hormonal pattern alterations, reduced or loss of libido,
      infertility, and impotence, thereby influencing their well-being. The pathogenic
      mechanisms include physiologic, psychologic, and organic causes. To determine the
      contribution of morphologic factors to impotence we studied the ultrastructure of
      the corpora cavernosa in 20 patients with end-stage renal disease who were
      treated with chronic dialysis and compared the findings with 6 individuals with
      no clinical history of impotence. Our results indicated that in male uremic
      patients with sexual disturbances there were major changes in smooth muscle
      cells. This was characterized by reduction of dense bodies in the cytoplasm,
      thick basement membranes, and increased interstitial collagen fibers with
      resultant reduction of cell-to-cell contact. In addition, there was thickening
      and lamination of basement membranes of endothelial cells and increased
      accumulation of collagen between nerve fibers. These alterations were more
      evident in patients with longer time on dialysis and were independent of type of
      primary renal disease. We hypothesize that ED in dialysis patients is not related
      to the primary disease but to the uremic state.

PMID- 15490418
TI  - The role of interleukin-6 and of its soluble receptors in the biocompatibility of
      dialysis treatment.
AB  - Proinflammatory cytokines, in addition to their role in host defence, may be
      considered mediators of disease; a reduction of cytokine synthesis or effects is,
      therefore, becoming a target of many diseases. IL-6 is a pro-inflammatory
      cytokine that may play a role in several clinical problems related to dialysis
      treatment. An enhanced spontaneous production of IL-6 by Peripheral Blood
      Mononuclear Cells (PBMC) harvested from ESRD patients dialyzed with a poor
      biocompatible membrane has been first demonstrated by our group. These results
      were also obtained in patients undergoing continuous peritoneal dialysis, in
      absence of peritonitis. We have also demonstrated that IL-6 release was inversely
      correlated with serum albumin changes. Biological activities of IL-6 may be
      modulated by two soluble circulating receptors, namely sIL-6R and sgp130. sIL-6R
      may enhance the inflammatory effects of IL-6 and is, therefore, an
      "agonistically" acting molecule. We have recently studied sIL-6R production in
      ESRD patients dialyzed with different membranes; the conclusion was that poor
      biocompatible membranes, via the sIL-6R, might further increase the inflammatory
      effects of IL-6. On the contrary, sgp130 can efficiently bind the IL-6/sIL-6R
      complex with "antagonistic" effects. We have evaluated plasma levels of sgp130 in
      18 ESRD patients regularly dialyzed with hemophan membranes (HE) and in 15
      patients dialyzed with more biocompatible synthetic membranes (BIO). Our results
      demonstrate that plasma levels of sgp130 in HE are 33% higher than in both
      healthy controls and BIO. Circulating levels of sgp130 were correlated positively
      with C-reactive protein (r: 0.338, p<0.05) and negatively with serum albumin (r: 
      0.334, p<0.05). These results suggest that higher circulating levels of sgp130
      are likely associated with higher IL-6 levels. These higher amounts are probably
      insufficient to control the activity of IL-6 and may be considered only as a
      marker of PBMC activation.

PMID- 15490419
TI  - Plasma levels of plasminogen activator inhibitor type 1, factor VIII, prothrombin
      activation fragment 1+2, anticardiolipin, and antiprothrombin antibodies are risk
      factors for thrombosis in hemodialysis patients.
AB  - Patients with end-stage renal disease are prone to hemorrhagic complications and
      simultaneously are at risk for a variety of thrombotic complications such as
      thrombosis of dialysis blood access, the subclavian vein, coronary arteries,
      cerebral vessel, and retinal veins, as well as priapism. The study was devised
      for the following purposes: (1) to identify the markers of thrombophilia in
      hemodialyzed patients, (2) to establish a role for antiphospholipid antibodies in
      thrombosis of the vascular access, (3) to characterize phospholipid antibodies in
      hemodialysis patients, and (4) to study the effects of dialysis on coagulation
      cascade. A group of 20 hemodialysis patients with no thrombotic complications
      (NTC) and 20 hemodialysis patients with thrombotic complications (TC) were
      studied along with 400 volunteer blood donors. Patients with systemic lupus
      erythematosus and those with nephrotic syndrome were excluded. All patients
      underwent a screening prothrombin time, activated partial thromboplastin time,
      fibrinogen (Fg), coagulation factors of the intrinsic and extrinsic pathways,
      antithrombin III (AT-III), protein C (PC), protein S (PS), resistance to
      activated protein C, prothrombin activation fragment 1+2 (F1+2), plasminogen,
      tissue type plasminogen activator (t-PA), plasminogen tissue activator inhibitor
      type-1 (PAI-1), anticardiolipin antibodies type M and G (ACA-IgM and ACA-IgG),
      lupus anticoagulant antibodies, and antiprothrombin antibodies type M and G (aPT
      IgM and aPT-IgG). The study showed that PAI-1, F 1+2, factor VIII, ACA-IgM, and
      aPT-IgM levels were increased significantly over controls both in TC and NTC,
      however, they could distinguish patients with thrombotic complications from those
      without, being increased maximally in the former group. The novelty of the study
      is represented by the significant aPT increase that was observed in non-systemic
      lupus erythematosus hemodialysis patients, and particularly in those with
      thrombotic events. In addition, there was a reduction of factor XII during the
      treatment. It is possible to assume in the TC group and, to a lesser extent, also
      in the NTC group that endothelial cells liberate PAI-1 in the vascular lumen,
      which causes hypofibrinolysis. In addition, an excess of factor VIII is activated
      by endothelial dysfunction with subsequent activation of the coagulation cascade
      as shown by increased F1+2 and fibrinogen. ACA-IgM, in turn, is capable of
      interfering with the system of protein C, a potent anticoagulant factor that
      inactivates cofactors Va and VIIIa. They also induce the expression of
      procoagulant factors on the surface of the endothelial cells. In conclusion, the
      hypercoagulable state caused by alterations of coagulation and fibrinolytic
      factors is a cause of vascular access dysfunction and thrombosis of other
      vessels.

PMID- 15490420
TI  - Advanced glycation end-products and peritoneal sclerosis.
AB  - Long-term continuous ambulatory peritoneal dialysis (CAPD) often causes
      peritoneal fibrosis and sclerosis with a loss of function, and some CAPD patients
      develop sclerosing encapsulating peritonitis. Glucose-based peritoneal dialysis
      fluids readily produce glucose degradation products by heat sterilization, and
      glucose degradation products accelerate the formation of advanced glycation end
      products (AGE) in the peritoneal cavity. The accumulation of AGE is observed in
      peritoneal mesothelial and submesothelial layers in CAPD patients, accompanied by
      enhanced expression of various growth factors and peritoneal thickening. The
      expression of transforming growth factor-beta1 (TGF-beta1), macrophage-colony
      stimulating factor, and vascular endothelial growth factor (VEGF) is distributed
      in the peritoneum similarly to that of AGE. In CAPD patients with low
      ultrafiltration (UF) capacity, peritoneal membrane is thickened owing to an
      increase in the number of cells such as fibroblasts and macrophages and collagen
      in the submesothelial layer. AGE is detected in the fibroblasts and macrophages
      as well as degenerated collagen. These cells in the submucosal layer are almost
      positive for the receptor for AGE (RAGE) and uptake AGE. The intensity of AGE
      accumulation and the expression of growth factors are associated with the
      severity of UF impairment. In fact, the accumulation of AGE and the expression of
      growth factors are recognized most markedly in the peritoneum of CAPD patients
      with low UF and sclerosing encapsulating peritonitis. In conclusion, long-time
      CAPD with heat-sterilized peritoneal dialysis fluid promotes AGE accumulation in
      the peritoneal membrane and alteration in peritoneal cell function and dialysis
      quality, followed by peritoneal sclerosis, and, finally, sclerosing encapsulating
      peritonitis.

PMID- 15490421
TI  - Continuum of therapy in progressive renal diseases (from predialysis to
      transplantation): analysis of a new organizational model.
AB  - In the aging of Western populations, decreased mortality is counterbalanced by an
      increase in morbidity, particularly involving chronic diseases such as most renal
      diseases. The price of the successful care of chronic conditions, such as
      cardiovascular diseases or diabetes, is a continuous increase in new dialysis
      patients. However, the increased survival of patients on chronic renal
      replacement therapies poses new challenges to nephrologists and calls for new
      models of care. Since its split from internal medicine, nephrology has seen a
      progressive trend toward super specialization and the differentiation into at
      least 3 major branches (nephrology, dialysis, and transplantation), following a
      path common to several other fields of internal medicine. The success in the care
      of chronic patients is owed not only to a careful technical prescription, but
      also to the ability to teach self-care and attain compliance; this requires good
      medical practice and a sound patient-physician relationship. In this context, the
      usual models of care may fail to provide adequate coordination and, despite
      valuable single elements, could end up as an orchestra without a conductor. We
      propose an integrated model of care oriented to the type of patient (tested in
      our area especially for diabetic patients): the patient is followed-up by the
      same team from the first signs of renal disease to eventual dialysis or
      transplantation. This model offers an interesting alternative both for patients,
      who usually seek continuity of care, and for nephrologists who prefer a holistic
      and integrated patient-physician approach.

PMID- 15490422
TI  - Vitamin E-coated dialyzer and antioxidant defense parameters: three-month study.
AB  - Atherosclerotic cardiovascular disease is the most frequent cause of death in
      patients with end-stage renal disease who have undergone dialysis treatment.
      Oxidative stress, increased lipid peroxidation, and impaired function of
      antioxidant systems may contribute to the accelerated development of
      atherosclerosis in chronic renal failure patients during renal replacement
      therapy. The aim of this study was to investigate the influence of a vitamin E
      coated dialyzer on antioxidant defense parameters in hemodialysis (HD) patients.
      In 14 HD patients, hemodialysis was performed using a vitamin E-coated dialyzer
      (Terumo CL-E15NL; Terumo Corporation, Tokyo, Japan) during a 3-month study. In
      these patients, erythrocyte (ER) antioxidant enzymes, superoxide dismutase (SOD),
      glutathione peroxidase (GPX), glutathione reductase (GR) and catalase (CAT),
      plasma total antioxidant capacity (TAC), RBC glutathione (GSH), plasma
      malondialdehyde (MDA), plasma, and RBC vitamin E were investigated. Each
      parameter was measured at the beginning of the study, after the 1st, 2nd, and 3rd
      month of the study, and 10 weeks after the interruption of the use of vitamin E
      coated dialyzer. All HD patients were treated by erythropoietin (EPO) and
      received vitamin C 50 mg/d, pyridoxine 20 mg/d, and folic acid 5 mg/wk during the
      entire study. The 3-month treatment with the vitamin E-coated dialyzer led to a
      significant decrease of plasma MDA level (from 2.85 +/- 0.44 to 2.25 +/- 0.37
      micromol/L) and to an increase of plasma TAC, RBC, GSH, and the vitamin E levels
      both in plasma (from 25.9 +/- 2.8 to 33.6 +/- 3.8 micromol/L) and in the RBCs
      (from 6.7 +/- 0.8 to 7.4 +/- 0.7 micromol/L) by 30% and 10.5%, respectively. Ten
      week interruption of the use of the vitamin E-coated dialyzer led to near initial
      values of MDA (2.90 +/- 0.28 micromol/L), plasma (28.6 +/- 3.5 micromol/L), and
      RBC (6.9 +/- 0.7 micromol/L) vitamin E and of other investigated parameters.
      Statistical analysis of results was performed by conventional methods and
      analysis of variance. The findings of the current study confirm the beneficial
      effect of the vitamin E-coated dialyzer against oxidative stress in HD patients.

PMID- 15490423
TI  - Chronic renal failure, dialysis, and renal transplantation in Anderson-Fabry
      disease.
AB  - Anderson-Fabry disease (AFd) is a rare, inherited, x-linked disease characterized
      by the deficiency of the lysosomal enzymatic alpha-galactosidase A activity
      (alpha-Gal-A). The enzyme defect leads to progressive accumulation of
      glycosphingolipids (GL) in all kinds of cells, tissues, organs, and body fluids.
      The clinical manifestations are very protean, the residual activity of alpha-Gal
      A and/or different gene mutations might explain different phenotypes, but as yet
      these concepts have not been proven. Usually, patients with AFd show 3 clinical
      phases, more evident in men than in heterozygous women. The first phase
      (childhood and adolescence) is characterized by myalgia, arthralgia,
      acroparesthesia, fever, cutaneous angiokeratomas, and corneal opacities. The
      second phase is characterized mainly by renal involvement. In the third phase,
      severe renal impairment and involvement of cerebrovascular and cardiovascular
      systems are present. The progression to end-stage renal disease (ESRD) is common
      in hemizygous males (3rd-5th decade of life); usually, death occurs because of
      cerebral and/or cardiovascular complications in patients undergoing chronic
      dialysis therapies. The survival of patients with AFd in dialysis is better than
      in diabetic patients, but it clearly is decreased compared with uremic patients
      with other nephropathies, despite a lower mean age of uremia (50 versus 60 y).
      The outcome of kidney transplantation is similar to that found in other patients
      with ESRD, despite controversial issues published in the past. The use of a
      kidney donor with normal alpha-Gal-A activity in the control of the metabolic
      systemic disease is unproven. The recurrence of GL deposits in the kidney graft
      has been documented rarely. The definitive treatment for AFd is enzyme
      replacement therapy with purified alpha-Gal-A produced by a genetically
      engineered human cell line or Chinese hamster oocytes: relatively short-term
      studies have shown a significant treatment effect on clinical outcome measures.

PMID- 15490424
TI  - Residual analysis in linear regression models with an interval-censored
      covariate.
AB  - Residual analysis is a useful class of techniques for the evaluation of the
      goodness of a fitted model. Checking the underlying assumptions is important
      since most linear regression estimators require a correctly specified regression
      function and independent and identically distributed errors to be consistent. For
      uncensored data, the examination of the residuals of the fitted model is a
      standard tool for checking whether or not the underlying model assumptions hold.
      Such analysis has not been widely developed for censored data. Hillis (Statistics
      in Medicine 1995; 14:2023-2036) developed a residual plot for model checking when
      the response variable of a linear model is right-censored, and Gomez et al.
      (Statistics in Medicine 2003; 22:409-425) proposed residuals in models with
      interval-censored covariates. In this paper, we propose a new definition of
      residuals for linear models that incorporate interval-censored covariates. This
      definition can be also applied when the response variable is interval-censored.
      These new residuals are shown to perform better in model checking than other
      types of residuals in this context. We illustrate them with a data set from an
      AIDS clinical trial study.

PMID- 15490425
TI  - Sample size formula for proportional hazards modelling of competing risks.
AB  - To test the effect of a therapeutic or prognostic factor on the occurrence of a
      particular cause of failure in the presence of other causes, the interest has
      shifted in some studies from the modelling of the cause-specific hazard to that
      of the subdistribution hazard. We present approximate sample size formulas for
      the proportional hazards modelling of competing risk subdistribution, considering
      either independent or correlated covariates. The validity of these approximate
      formulas is investigated through numerical simulations. Two illustrations are
      provided, a randomized clinical trial, and a prospective prognostic study.

PMID- 15490426
TI  - Adjusting the generalized ROC curve for covariates.
AB  - Receiver operating characteristic (ROC) curves and in particular the area under
      the curve (AUC), are widely used to examine the effectiveness of diagnostic
      markers. Diagnostic markers and their corresponding ROC curves can be strongly
      influenced by covariate variables. When several diagnostic markers are available,
      they can be combined by a best linear combination such that the area under the
      ROC curve of the combination is maximized among all possible linear combinations.
      In this paper we discuss covariate effects on this linear combination assuming
      that the multiple markers, possibly transformed, follow a multivariate normal
      distribution. The ROC curve of this linear combination when markers are adjusted
      for covariates is estimated and approximate confidence intervals for the
      corresponding AUC are derived. An example of two biomarkers of coronary heart
      disease for which covariate information on age and gender is available is used to
      illustrate this methodology.

PMID- 15490427
TI  - Placebo-free designs for evaluating new mental health treatments: the use of
      adaptive treatment strategies.
AB  - The dominant pre-marketing clinical trial in psychopharmacology is a non
      equivalence design that randomizes patients to one of three treatments: an
      accepted standard, the innovation (new drug), or placebo, with the main efficacy
      comparison being innovation vs placebo. The reasons behind the choice of placebo
      control in new drug development include anticipated small effect size for active
      controlled comparisons and the sufficiency of demonstrated treatment effect (new
      drug vs placebo) for regulatory approval. These reasons have led to great
      reliance on placebo control in drug evaluation studies, despite the ethical
      controversy over the use of placebo when there are known effective standard
      treatments. While the use of placebo controls has been widely debated, a less
      considered aspect of the usual placebo-controlled non-equivalence design is the
      disparity between the decisions that it supports and those that pervade clinical
      practice. We propose an alternative approach that randomizes one group of
      patients to an adaptive treatment strategy that exemplifies the adaptive nature
      of clinical decision-making in the treatment of ongoing mental health disorders.
      The basic idea is to compare the adaptive strategy, which uses a patient's
      outcomes to date to determine when to switch from an initial treatment (e.g. an
      accepted standard) to an alternative (e.g. the new) treatment, to fixed trials of
      either treatment option. We state the conditions under which the adaptive
      treatment RCT is attractive to implement and the requirements for doing so.

PMID- 15490428
TI  - The role of cancer worry in cancer screening: a theoretical and empirical review
      of the literature.
AB  - This paper reviews findings regarding the influence of cancer worry on cancer
      screening behaviors. The role of cancer worry in motivating cancer screening has
      been pursued for over 30 years. Recent concerns that high levels of cancer worry
      may impede the screening behavior of high-risk individuals have further
      prioritized this area of research. Despite heavy attention in the literature,
      there is currently no theoretical or empirical consensus concerning whether
      cancer worry motivates or inhibits cancer screening behaviors. We focus the
      review on four questions: (1) What is cancer worry? (2) To what extent are people
      worried about cancer? (3) What are the predominant theoretical approaches to
      understanding the role of cancer worry in cancer screening behaviors? (4) What is
      the empirical evidence for the role of cancer worry in cancer screening
      behaviors? We identify factors that have hampered theoretical and empirical
      advancement, including divergent definitions and measurement strategies for
      cancer worry, low to moderate levels of cancer worry even among those at high
      risk, and a reliance on cross-sectional research designs. The review clarifies
      the current state of this literature, and proposes future research strategies,
      including an expanded emphasis on cancer worry and cancer screening among men and
      diverse racial/ethnic groups.

PMID- 15490430
TI  - Bootstrap confidence intervals for medical costs with censored observations.
AB  - Medical costs data with administratively censored observations often arise in
      cost-effectiveness studies of treatments for life-threatening diseases. Mean of
      medical costs incurred from the start of a treatment until death or a certain
      time point after the implementation of treatment is frequently of interest. In
      many situations, due to the skewed nature of the cost distribution and non
      uniform rate of cost accumulation over time, the currently available normal
      approximation confidence interval has poor coverage accuracy. In this paper, we
      propose a bootstrap confidence interval for the mean of medical costs with
      censored observations. In simulation studies, we show that the proposed bootstrap
      confidence interval had much better coverage accuracy than the normal
      approximation one when medical costs had a skewed distribution. When there is
      light censoring on medical costs (< or =25 per cent), we found that the bootstrap
      confidence interval based on the simple weighted estimator is preferred due to
      its simplicity and good coverage accuracy. For heavily censored cost data
      (censoring rate > or =30 per cent) with larger sample sizes (n > or =200), the
      bootstrap confidence intervals based on the partitioned estimator has superior
      performance in terms of both efficiency and coverage accuracy. We also illustrate
      the use of our methods in a real example.

PMID- 15490431
TI  - Enhanced specificity of bacterial spore identification by oxidation and mass
      spectrometry.
AB  - Addition of an oxidizing agent (e.g., hydrogen peroxide) to intact spores
      selectively and completely oxidizes Met-containing biomarker proteins by
      formation of Met sulfoxides. This reaction increases the masses of the biomarker
      proteins observed in matrix-assisted laser desorption/ionization mass
      spectrometry (MALDI-MS) of Bacillus spores by Deltam = (16 x n) Da, where n is
      the number of Met residues in the sequence of each individual protein. The
      procedure is very rapid, and can be performed in situ (i.e., on the MALDI
      target). It confirms the identity of individual biomarkers by comparing the
      number of Met amino acids from the experimentally determined mass shifts with
      predictions for n from the tentative amino acid sequence for each protein. In
      turn, accurate determination of n for several biomarkers allows rapid validation
      of the initial spore identification by MALDI-MS.

PMID- 15490432
TI  - The analysis of repeated 'direct' measures of change illustrated with an
      application in longitudinal imaging.
AB  - The use of repeated measures of an outcome variable to improve statistical power
      and precision in randomized clinical trials and cohort studies is well
      documented. Linear mixed models have great utility in the analysis of such
      studies in many medical applications including imaging. However, in imaging
      studies and other applications the basic outcome can be a 'direct' measure of
      change in a variable, as opposed to a difference calculated by subtraction of one
      measured value from another. The correlation structure of such repeated measures
      of 'direct' change, in particular the non-independence of within-person
      consecutive measures, adds complexity to the analysis. In this paper, we present
      a family of hierarchical mixed models for the analysis of such data and explain
      how to implement them using standard statistical software. We illustrate the use
      of our models with data from a cohort of patients with Alzheimer's disease.

PMID- 15490433
TI  - Power and sample size determination when assessing the clinical relevance of
      trial results by 'responder analyses'.
AB  - A fundamental issue in regulatory decision making is the assessment of the
      benefit/risk profile of a compound. In order to do this, establishing the
      existence of a treatment effect by a significance test is not sufficient, but the
      clinical relevance of a potential benefit must also be taken into account. A
      number of regulatory guidelines propose that clinical relevance should be
      assessed by considering the rate of responders, i.e. the proportion of patients
      who are observed to achieve an apparently meaningful benefit. In this paper, we
      present methods for planning clinical trials that aim at demonstrating both
      statistical and clinical significance in superiority trials. Procedures based on
      analytical calculations are derived for normally distributed data and the case of
      a single endpoint as well as multiple primary outcomes. A bootstrap procedure is
      proposed that can be applied to non-normal data. Application is illustrated by a
      clinical trial in Alzheimer's disease.

PMID- 15490434
TI  - Spectrophotometric determination of deacetylation degree of chitinous materials
      dissolved in phosphoric acid.
AB  - A simple spectrophotometric method is proposed for determining deacetylation
      degrees (DD) of chitinous materials using phosphoric acid as the UV-transparent
      solvent system. Calibrating by the extinction coefficients (A(210)) of D
      glucosamine and N-acetyl-D-glucosamine, DD values (24-88%) were computed
      numerically. The results correlated well (R(2) = 0.9805, n = 50) with those
      obtained by solid-state (13)C NMR. Comparison of the results obtained by the
      proposed UV method and solid-state (13)C NMR.

PMID- 15490435
TI  - Enantiomer discrimination of peptides by tandem mass spectrometry: influence of
      the peptide sequence on chiral recognition.
AB  - The enantiomer discrimination of peptides by electrospray ionization tandem mass
      spectrometry is described. A cinchona alkaloid derivative, tert
      butylcarbamoylquinine, is used as chiral selector. The chiral selector forms
      diastereomeric complexes with the peptide enantiomers in the liquid phase
      (methanolic solution), which are then transferred to the gas phase, where their
      dissociation behaviour is studied in an ion-trap mass spectrometer. Different
      degrees of dissociation of the diastereomeric complexes allow for the
      discrimination of the peptide enantiomers. The influence of the peptide sequence
      on enantiomer discrimination is discussed and molecular recognition information
      is derived by comparing the results obtained for related peptides. For
      dipeptides, small amino acid residues at the N-terminus and bulky side chains at
      the C-terminus were found to enhance chiral recognition, while for tripeptides
      the effects were rather irregular.

PMID- 15490436
TI  - Comparing regression methods for the two-stage clonal expansion model of
      carcinogenesis.
AB  - In the statistical analysis of cohort data with risk estimation models, both
      Poisson and individual likelihood regressions are widely used methods of
      parameter estimation. In this paper, their performance has been tested with the
      biologically motivated two-stage clonal expansion (TSCE) model of carcinogenesis.
      To exclude inevitable uncertainties of existing data, cohorts with simple
      individual exposure history have been created by Monte Carlo simulation. To
      generate some similar properties of atomic bomb survivors and radon-exposed mine
      workers, both acute and protracted exposure patterns have been generated. Then
      the capacity of the two regression methods has been compared to retrieve a priori
      known model parameters from the simulated cohort data. For simple models with
      smooth hazard functions, the parameter estimates from both methods come close to
      their true values. However, for models with strongly discontinuous functions
      which are generated by the cell mutation process of transformation, the Poisson
      regression method fails to produce reliable estimates. This behaviour is
      explained by the construction of class averages during data stratification.
      Thereby, some indispensable information on the individual exposure history was
      destroyed. It could not be repaired by countermeasures such as the refinement of
      Poisson classes or a more adequate choice of Poisson groups. Although this choice
      might still exist we were unable to discover it. In contrast to this, the
      individual likelihood regression technique was found to work reliably for all
      considered versions of the TSCE model.

PMID- 15490437
TI  - Transformation of biodegradable polyesters into cyclic oligomers under continuous
      flow using an enzyme-packed column.
AB  - The enzymatic degradation of typical chemically synthesized biodegradable
      plastics, such as poly(butylene adipate) and poly(epsilon-caprolactone), to a
      repolymerizable cyclic oligomer under continuous flow using an enzyme column was
      studied, directed towards green chemical recycling. It was confirmed that both
      polymers were quantitatively transformed into the corresponding cyclic oligomers
      by passage through the column packed with immobilized lipase from Candida
      antarctica (Novozym 435) at 40 degrees C using a toluene solution. Compared to
      the batch treatment in a flask, a short reaction time and a low reaction
      temperature occurred for complete transformations of the polyesters by continuous
      flow through the enzyme column. The degradation activity of the enzyme column was
      maintained for at least six months at 40 degrees C. Conceptual scheme of the
      continuous degradation equipment using the enzyme column.

PMID- 15490438
TI  - Electrochemical detector based on sol-gel-derived carbon composite material for
      capillary electrophoresis microchips.
AB  - An on-chip disk electrode based on sol-gel-derived carbon composite material
      could be easily and reproducibly fabricated. Unlike other carbon-based electrodes
      reported previously, this detector is rigid, convenient to fabricate, and
      amenable to chemical modifications. Based on the stable and reproducible
      characters of this detector, a copper particle-modified detector was developed
      for the detection of carbohydrates which extends the application of the carbon
      based electrode. In our experiments, the performance of the new integrated
      detector for rapid on-chip measurement of epinephrine and glucose was
      illustrated. Experimental procedures including the fabrication of this detector,
      the configuration of separation channel outlet and electrode verge, and the
      performance characteristics of this new electrochemical detector were
      investigated.

PMID- 15490439
TI  - Capillary isoelectric focusing-mass spectrometry for shotgun approach in
      proteomics.
AB  - We report on capillary isoelectric focusing-mass spectrometry (CIEF-MS) of
      complex peptide mixtures in the absence of carrier ampholytes. Furthermore, the
      use of low concentrations of carrier ampholytes as mere spacers is investigated.
      Carrier ampholytes are complex mixtures of amphoteric compounds with high
      buffering capacity. Since all peptides are amphoteric compounds by themselves,
      the use of carrier ampholytes may be superfluous to establish a stable pH
      gradient in CIEF analysis of protein digests. Our research showed that when
      carrier ampholytes are omitted, the analyte ions are not focused at their
      isoelectric point. The analytes are charged, leading to electrophoretic mobility
      uncharacteristic for CIEF. The method was tested for a five-protein-mixture at
      0.02 mg/mL per protein and 0.05 mg/mL per protein. At the lower concentration,
      the analytes were stacked during the focusing process in only a limited length of
      the capillary. Therefore, the higher concentration led to better separation
      efficiency. It was found that at low concentration (0.20%) the carrier ampholytes
      could work as spacers. Though it led to sensitivity losses of 15-45%, this was
      compensated by the higher separation efficiencies seen. The method was evaluated
      with an eight-protein-mixture, of which all could be identified after performing
      MS/MS.

PMID- 15490440
TI  - Membrane proteome analysis of the green-sulfur bacterium Chlorobium tepidum.
AB  - An extensive proteomic approach relies on the possibility to visualize and
      analyze various types of proteins, including membrane proteins, which are rarely
      detectable on two-dimensional electrophoresis gels. In this study, different
      methods were employed for the enrichment of membrane proteins from Chlorobium
      tepidum prior to analysis with two-dimensional electrophoresis (2-DE). Isolated
      membranes were solubilized with Triton X-100 and from the supernatant we
      identified 58 unique proteins. The use of ionic sodium dodecyl sulfate (SDS) for
      protein solubilization, combined with acetone precipitation, resulted in an
      improved 2-DE pattern and the total number of the identified proteins was
      increased to 117. The use of acetone for protein precipitation improved the
      results by extracting compounds potentially deleterious to the resolution of 2
      DE. However, the additional proteins detected by the use of SDS are in the
      majority more difficult to solubilize than less hydrophobic proteins. Further our
      attempts for selective extraction of the outer membrane proteins using the acid
      glycine method allowed the identification of 37 proteins of which 14 were
      predicted to have a signal sequence indicating their localization in the
      periplasmic space or in the outer membrane.

PMID- 15490442
TI  - Asymmetric ABC-triblock copolymer membranes induce a directed insertion of
      membrane proteins.
AB  - Asymmetric molecules and materials provide an important basis for the
      organization and function of biological systems. It is well known that, for
      example, the inner and outer leaflets of biological membranes are strictly
      asymmetric with respect to lipid composition and distribution. This plays a
      crucial role for many membrane-related processes like carrier-mediated transport
      or insertion and orientation of integral membrane proteins. Most artificial
      membrane systems are, however, symmetric with respect to their midplane and
      membrane proteins are incorporated with random orientation. Here we describe a
      new approach to induce a directed insertion of membrane proteins into asymmetric
      membranes formed by amphiphilic ABC triblock copolymers with two chemically
      different water-soluble blocks A and C. In a comparative study we have
      reconstituted His-tag labeled Aquaporin 0 in lipid, ABA block copolymer, and ABC
      block copolymer vesicles. Immunolabeling, colorimetric, and fluorescence studies
      clearly show that a preferential orientation of the protein is only observed in
      the asymmetric ABC triblock copolymer membranes.

PMID- 15490443
TI  - High-speed DNA sequencing by tube-based capillary electrophoresis.
AB  - We assessed the feasibility of high-speed DNA sequencing by tube-based capillary
      electrophoresis (TCE) with electrokinetic sample injections. We developed a water
      circulated TCE system to control the capillary temperature precisely. Using this
      system and a ready-made sieving matrix at 50 degrees C, single-stranded DNA size
      marker fragments were separated at various pairs of the electric field strength,
      E, of 128-480 V/cm and the capillary effective length, L, of 100-360 mm. Assuming
      the read length (RL) is the fragment size at which the peak width equals the peak
      interval per base in obtained electropherograms, we estimated the values of RL
      (E, L), the RL at the pair (E, L). The points in ELz-space, (E, L, RL(E, L)),
      form a curved surface expressed by z = RL(E, L). Analyzing the contour lines of
      this curved surface, we determined the pairs of E and L providing target RLs of
      300-500 bases within a minimum time. At a pair optimized for a 500-base RL (330
      V/cm, 200 mm), one-color sequencing fragments were successfully separated up to
      529 bases within 9.6 min. These results demonstrate that high-speed DNA
      sequencing comparable with that obtained by microfabricated chip-based capillary
      electrophoresis (MCE) can be achieved with TCE, which is more suitable in
      automation than MCE.

PMID- 15490444
TI  - Fundamental aspects of contactless conductivity detection for capillary
      electrophoresis. Part I: Frequency behavior and cell geometry.
AB  - A better understanding of the characteristics of the axial contactless
      conductivity cell could be obtained by carefully studying the effect of the cell
      geometry on its frequency behavior. A good fit between theoretical and
      experimental results shows that the axial contactless conductometric detector can
      effectively be described by the simplest possible equivalent circuitry consisting
      of a capacitor, resistor, and a second capacitor. The cell constant is largely
      defined by the length of the gap between the electrodes. The effective electrode
      size is thus not related to the dimensions of the real electrodes but more
      closely to the cross-sectional area of the internal diameter of the capillary.
      Typical experimental values of 20 MOmega and 0.1 pF were obtained for the
      resistance and capacitances, respectively, of a cell formed by a 2 mm gap between
      two 4 mm long electrodes fitted with a capillary of 50 microm ID. It could be
      shown that the diameter of the electrode is not critical and tight coupling of
      the electrodes to the outer wall of the capillary is not needed. The peak
      overshoot phenomenon, which has frequently been reported, is an artefact that can
      be minimized by optimizing the frequency for cell excitation. The frequency
      setting has to be optimized for each cell design, operational amplifier,
      electrolyte solution and capillary.

PMID- 15490445
TI  - Fundamental aspects of contactless conductivity detection for capillary
      electrophoresis. Part II: Signal-to-noise ratio and stray capacitance.
AB  - The signal-to-noise ratio of a contactless conductivity detector for capillary
      electrophoresis was examined for different cell arrangements and operating
      parameters. The best signal-to-noise ratios, and hence the best detection limits,
      are obtained for frequencies which give highest sensitivity. Comparative
      experiments for three different excitation voltages (20, 100, and 200 V(pp))
      showed that the best signal-to-noise ratios were achieved for the highest
      excitation voltage of 200 V(pp). Low conductivity of the background electrolyte
      solution is mandatory to obtain lowest noise levels, and also the improvement on
      applying high excitation voltages was best for the electrolyte solution with
      lowest conductivity. The diameter of the electrodes was found to have only a
      negligible effect, so that a tight fitting of the electrodes to the external
      diameter of the capillary is not necessary. A cell without shielding between the
      two electrodes showed significant direct coupling (stray capacitance) and lower
      signal-to-noise ratios for all experimental conditions used. A serious distortion
      of the peak shapes was also observed for this cell arrangement.

PMID- 15490446
TI  - Importance of the counterion in optimization of a borate electrolyte system for
      analyses of anions in samples with complex matrices performed by capillary zone
      electrophoresis.
AB  - Borate buffers are common background electrolytes for analyses of anions in
      capillary zone electrophoresis. Usually, sodium borate at a given pH is used and
      this specification seems to be sufficient for a successful analysis. In this
      paper, we show that free migration of OH(-) may deteriorate the analysis of a
      typical anionic analysis of clinical samples due to uncontrolled migration of OH(
      ) throughout the systems of analyzed zones and may damage the stacking of anionic
      analytes of interest. We have proven that the use of ammonium borate may remedy
      the situation where the presence of ammonium may selectively stop the free
      migration of OH(-) ions, slow down their effective mobility and bring their safe
      behavior resulting in reproducible stacking of clinically important anions.
      Results of real analyses of human serum samples confirmed the proposed method and
      proved that substitution of sodium for ammonium in borate buffers offers reliable
      analyses of clinical samples having chloride as the bulk component. The
      experimental results given in this paper are supported also by computer
      simulation, which can not only support the positive results but also show the
      dynamics of the separation that is otherwise hidden to any detection
      possibilities.

PMID- 15490447
TI  - Quantitative measurement of collagen methylation by capillary electrophoresis.
AB  - Collagen methylation has been exploited in various applications involving living
      cells. We have observed correlation between the collagen methylation with the
      rate of cell proliferation in three-dimensional (3-D) microenvironment. To
      quantify the degree of collagen methylation, we have developed a capillary zone
      electrophoresis method. Using a polyvinyl alcohol-coated fused-silica capillary
      and UV detection at 200 nm, we have optimized pH and separated the native
      collagen into three major bands in phosphate buffer (50 mM, pH 2.5) with 0.05%
      hydroxypropylmethylcellulose. Under these conditions, the methylated collagens
      were separated into four major bands, which changed with different methylation
      reaction conditions. We propose an index to quantify the degree of collagen
      methylation that also correlates with their effects on cell proliferation.

PMID- 15490448
TI  - Drug-human serum albumin binding studied by capillary electrophoresis with
      electrochemiluminescence detection.
AB  - A new technique for investigating drug-protein binding was developed employing
      capillary electrophoresis (CE) coupled with tris(2,2'-bipyridyl) ruthenium(II)
      [Ru(bpy)(3) (2+)] electrochemiluminescence (ECL) (CE-ECL) detection after
      equilibrium dialysis. Three basic drugs, namely pridinol, procyclidine and its
      analogue trihexyphenidyl, were successfully separated by capillary zone
      electrophoresis with end-column Ru(bpy)(3) (2+) ECL detection. The relative drug
      binding to human serum albumin (HSA) for each single drug as well as for the
      three drugs binding simultaneously was calculated. It was found that the three
      antiparkinsonian drugs compete for the same binding site on HSA. This work
      demonstrated that Ru(bpy)(3) (2+) CE-ECL can be a suitable technique for studying
      drug-protein binding.

PMID- 15490449
TI  - Direct automatic determination of biogenic amines in wine by flow injection
      capillary electrophoresis-mass spectrometry.
AB  - A capillary electrophoresis-electrospray mass spectrometry (CE-ESI-MS) method for
      the separation and determination of nine biogenic amines is proposed. Operational
      variables, such as the voltage, temperature, sheath liquid composition, flow
      rate, and MS parameters, were optimized. Samples are injected in the hydrodynamic
      mode into a 75 cm x 50 microm ID coated capillary and separated by using 25 mM
      citric acid at pH 2.0. Heptylamine is used as internal standard. The experimental
      setup includes a flow manifold coupled to the CE system for automatic insertion
      of samples into the CE vials. The proposed method allows amines to be determined
      with limits of detection from 0.018 to 0.09 microg x mL(-1) and relative standard
      deviation (RSD) values from 2.4% to 5.0% (except 6.8% for histamine). The method
      was successfully used to determine biogenic amines in red and white wines.

PMID- 15490450
TI  - Chemical analysis of raw, dry-roasted, and honey-roasted licorice by capillary
      electrophoresis.
AB  - In herbal medicine, licorice is usually processed using a roasting procedure
      which might modify the chemical compositions in licorice. To test this
      hypothesis, licorice root samples were roasted under various conditions (with or
      without honey) and subsequently extracted by refluxing with 95% ethanol. The
      analysis of chemical compositions of licorice root extracts was achieved by
      capillary electrophoresis. The running buffer has been optimized to be 50 mM
      sodium tetraborate (pH 9.01) containing 5 mM beta-cyclodextrin. Thermal
      decomposition of glycyrrhizin, which was a major ingredient in licorice, was
      first studied in detail, indicating the conversion of glycyrrhizin to
      glycyrrhetinic acid. The licorice extracts were then analyzed to indicate the
      above thermal conversion did occur in the licorice samples. This finding may shed
      some light on understanding the differences in the therapeutic values of raw
      versus roasted licorice in herbal medicine.

PMID- 15490451
TI  - Determination of some acidic drugs in surface and sewage treatment plant waters
      by capillary electrophoresis-electrospray ionization-mass spectrometry.
AB  - We describe an analytical method involving solid-phase extraction (SPE) and
      capillary zone electrophoresis-electrospray ionization-mass spectrometry (CZE-ESI
      MS) for determining some pharmaceutical compounds - naproxen, clofibric acid and
      bezafibrate - in real water samples. The electrospray parameters were optimized
      to maximize sensitivity. When a mixed aqueous-organic solvent and CZE-ESI-MS were
      used to analyze these drugs in water samples, the capillary was coated with
      hexadimethrin bromide (HDB) to permanently reverse the EOF. The method was
      developed from off-line SPE-CZE-MS and was validated with surface water. The
      detection limits were 100 ng.L(-1) for all analytes. The method was applied to
      analyze water samples from the influent and effluent of a sewage treatment plant.
      A liquid-liquid extraction step was required before SPE, and the compounds
      studied were found, some of them between detection and quantification limits.

PMID- 15490452
TI  - Capillary electrophoretic separation of cationic constituents of imidazolium
      ionic liquids.
AB  - A capillary electrophoretic method for resolving selected imidazolium ionic
      liquid cations is reported. The method, in which citric buffer is used as the
      running electrolyte, is simple and reproducible. The separation of a standard
      mixture is in linear accordance with the relative molecular mass (M(r)) of
      solutes regardless of the type of substitution (alkyl or aryl). The theoretical
      prediction of compounds as yet not analyzed is therefore possible; however,
      cations with identical molecular masses are inseparable with this method.
      Nevertheless, the method's quantitative analytical performance was excellent. The
      paper also discusses the applicability of a method for tracking the
      photodegradation kinetics of an exemplary ionic liquid.

PMID- 15490454
TI  - High-buffering capacity, hydrolytically stable, low-pI isoelectric membranes for
      isoelectric trapping separations.
AB  - Hydrolytically stable, low-pI isoelectric membranes have been synthesized from
      low-pI ampholytic components, poly(vinyl alcohol), and a bifunctional cross
      linker, glycerol-1,3-diglycidyl ether. The low-pI ampholytic components used
      contain one amino group and at least two weakly acidic functional groups. The
      acidic functional groups are selected such that the pI value of the ampholytic
      component is determined by the pK(a) values of the acidic functional groups. When
      the concentration of the ampholytic component incorporated into the membrane is
      higher than a required minimum value, the pI of the membrane becomes independent
      of variations in the actual incorporation rate of the ampholytic compound. The
      new, low-pI isoelectric membranes have been successfully used as anodic membranes
      in isoelectric trapping separations with pH < 1.5 anolytes and replaced the
      hydrolytically less stable polyacrylamide-based isoelectric membranes. The new
      low-pI isoelectric membranes have excellent mechanical stability, low electric
      resistance, good buffering capacity, and long life time, even when used with as
      much as 50 W power and current densities as high as 33 mA/cm(2) during the
      isoelectric trapping separations.

PMID- 15490455
TI  - Catching protein antigens by antibody affinity electrophoresis.
AB  - A new kind of affinity electrophoresis called antibody affinity electrophoresis
      is a technique used to capture protein antigens based on their interactions with
      specific monoclonal or polyclonal antibodies incorporated in the polyacrylamide
      gel. Polyclonal anti-glutathione-S-transferase (anti-GST), monoclonal anti-bovine
      serum albumin (anti-BSA), and polyclonal anti-human alpha-lactalbumin are
      embedded in distinct areas of a 7.5% native polyacrylamide gel. Some of the
      embedded antibodies get covalently and/or noncovalently incorporated into the gel
      matrix network. Under electrophoresis conditions, these antibodies do not show
      significant electrophoretic mobility, as compared to their specific protein
      antigen analytes. We observed that electrophoretic migration of GST, BSA, and
      protein G ceases when they encounter anti-GST, anti-BSA, and immunoglobulin G,
      respectively.

PMID- 15490456
TI  - Electrophoretic separation of amyloid beta peptides in plasma.
AB  - In this prospective study, for the first time we have separated and quantified
      amyloid beta (Abeta) peptides in the plasma of patients with Alzheimer's disease
      (AD, n = 8) and age- and environment-matched healthy controls (n = 9) with urea
      based Abeta-sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE)/immunoblot. In addition to the Abeta peptides 1-37/38/39/40/42, which we
      recently identified as regular constituents of human cerebrospinal fluid (CSF),
      we have observed a novel electrophoretic band migrating slightly cathodically to
      Abeta1-42. Since a standard peptide with the amino acid sequence Abeta2-40
      migrates in the same position, we hypothesize that this plasma-specific band may
      correspond to Abeta2-40. The concentration of Abeta peptides in the plasma has
      been approximately 100-fold lower compared to the CSF. Interestingly, the
      concentration of the two shortest peptides and the longest one of these
      considered here (i.e., Abeta1-37/38/42) have increased significantly when the
      samples have been frozen at -80 degrees C before immunoprecipitation, while the
      'middle-length' peptides (i.e., Abeta1-39/40) have not been affected by this
      procedure. We have not observed significant differences of the Abeta peptides
      concentrations between AD and control subjects. Our method can be used to
      investigate the significance of plasma Abeta peptides in neurodegenerative
      disorders, and to monitor the efficiency of drugs with beta/gamma-secretase
      inhibitory potency.

PMID- 15490457
TI  - Haplotype studies support slippage as the mechanism of germline mutations in
      short tandem repeats.
AB  - Germline mutations of human short tandem repeat (STR) loci are expansions or
      contractions of repeat arrays which are not well understood in terms of the
      mechanism(s) underlying such mutations. Although polymerase slippage is generally
      accepted as a mechanism capable to explain most features of such mutations, it is
      still possible that unequal crossing over plays some role in those events, as
      most studies in humans could not exclude unequal crossing over (UCO). Crossing
      over can be studied by analyzing haplotypes using flanking markers. To check for
      UCO in mutations, we have analyzed 150 paternity cases for which more than the
      usual trio (mother, child, and father) were available for testing by analyzing 16
      STR loci. In a total of 4900 parent-child allele transfers four mutations were
      observed at different loci (D8S1179, D18S51, D21S11, and SE33/ACTBP2). To
      identify the mutated allele and to check for UCO, we typed at least four
      informative loci flanking the mutated locus and used the pedigree data to
      establish haplotypes. By doing so we were able to exclude UCO in each case.
      Moreover, we were able to identify the mutations as one-repeat
      contractions/expansions. Our data thus support slippage as the mechanism of
      germline mutations in STRs.

PMID- 15490458
TI  - Systematic multiplex polymerase chain reaction and reverse transcription
      polymerase chain reaction analyses of changes in copy number and expression of
      proto-oncogenes and tumor suppressor genes in cancer tissues and cell lines.
AB  - Systematic multiplex reverse transcription-polymerase chain reaction (SM RT-PCR)
      is distinguishable from other multiplex RT-PCR methods by (i) utilization of
      primers that amplify sequences that fall within a single exon of the genes, (ii)
      utilization of genomic DNA as a calibration standard, and (iii) optimized PCR
      conditions that allow amplification of bands of similar intensity using genomic
      DNA template. We previously developed the human experimental systems of 68
      glycosyltransferase genes, 39 Hox genes, and 26 integrin subunit genes, and
      analyzed the expression of those genes in human adult tissues. Here we report the
      establishment of an SM RT-PCR system of proto-oncogenes and tumor suppressor
      genes and the analysis of gene expression in human cancer tissues and cell lines.
      We also demonstrate that the SM RT-PCR system, which was developed for cDNA
      expression analysis, could also be used successfully for more exquisite analysis
      of copy number changes in genomic DNA. We observed a decrease in band intensity
      of HRAS, TP73, CDKN2A, and CDKN2B genes in most of the breast and prostate cancer
      cell lines examined. The decrease in copy number of HRAS proto-oncogene leads us
      to suspect the presence of tumor suppressor genes in the vicinity of this gene on
      chromosome 11p15.5.

PMID- 15490459
TI  - Nonisotopic single-strand conformation polymorphism analysis of sequence
      variability in ribosomal DNA expansion segments within the genus Trichinella
      (Nematoda: Adenophorea).
AB  - A nonisotopic single-strand conformation polymorphism (SSCP) approach was
      employed to 'fingerprint' sequence variability in the expansion segment 5 (ES5)
      of domain IV and the D3 domain of nuclear ribosomal DNA within and/or among
      isolates and individual muscle (first-stage) larvae representing all currently
      recognized species/genotypes of Trichinella. In addition, phylogenetic analyses
      of the D3 sequence data set, employing three different tree-building algorithms,
      examined the relationships among all of them. These analyses showed strong
      support that the encapsulated species T. spiralis and T. nelsoni formed a group
      to the exclusion of the other encapsulated species T. britovi and its related
      genotypes Trichinella T8 and T9 and T. murrelli, and T. nativa and Trichinella
      T6, and strong support that T. nativa and Trichinella T6 grouped together. Also,
      these eight encapsulated members grouped to the exclusion of the nonencapsulated
      species T. papuae and T. zimbabwensis and the three representatives of T.
      pseudospiralis investigated. The findings showed that nonencapsulated species
      constitute a complex group which is distinct from the encapsulated species and
      supported the current hypothesis that encapsulated Trichinella group external to
      the nonencapsulated forms, in accordance with independent biological and
      biochemical data sets.

PMID- 15490460
TI  - Description of an ultrathin multiwire proportional chamber-based detector and
      application to the characterization of the Spraguea lophii (Microspora) two
      dimensional genome fingerprint.
AB  - Multiwire proportional chamber is a useful technology to build detectors that
      supersede the lack of interactivity of autoradiography in molecular biology
      experiments. Some drawbacks still limited the diffusion of existing instruments
      in biological laboratories. The major competitors are storage phosphor imaging
      systems. The simplified description of a radio-chromato-imager prototype (RCI)
      based on an original ultrathin multiwire proportional chamber is presented. It
      combines the advantage of the different existing technologies to present
      competitive properties in terms of efficiency, spatial resolution, robustness,
      manipulation easiness and production cost. Application of the RCI detector to
      molecular biology was performed by the analysis of karyotype and restriction
      display two-dimensional pulsed-field gel electrophoresis (KARD 2-D PFGE) data
      which are used to describe small eukaryotic genome structures. The comparative
      analysis with autoradiography was performed with the PDQuest software on Spraguea
      lophii (Microspora) genome fingerprints. The spot detection procedure applied to
      the different images leads to a similar conclusion considering the genome
      structure of S. lophii which appeared to be composed of 15 chromosomes for 13
      karyotypic bands (200-880 kbp).

PMID- 15490461
TI  - Multiple small doses of levodopa plus entacapone produce continuous dopaminergic
      stimulation and reduce dyskinesia induction in MPTP-treated drug-naive primates.
AB  - Long-acting dopamine agonist drugs induce a lower incidence of dyskinesia in MPTP
      treated primates and patients with Parkinson's disease compared to pulsatile
      treatment with levodopa, supporting the concept of continuous dopaminergic
      stimulation as a means of dyskinesia avoidance. We examined the effects of L-dopa
      administered with or without the COMT inhibitor entacapone on dyskinesia
      induction in previously untreated MPTP-treated common marmosets. Administration
      of L-dopa (12.5 mg/kg p.o.) plus carbidopa twice daily produced fluctuating
      improvement in motor behavior coupled with dyskinesia. Coadministration with
      entacapone produced similar patterns of motor improvement and dyskinesia that
      were not different from that produced by L-dopa alone. Treatment with L-dopa
      (6.25 mg/kg p.o.) plus carbidopa four times daily reversed motor disability and
      induced dyskinesia in a manner that was not different from the twice-daily
      treatment regimens. However, coadministration with entacapone produced more
      continuous improvement in locomotor activity with less dyskinesia than animals
      treated with L-dopa four times daily alone. These data support the notion that
      pulsatile stimulation contributes to the development of dyskinesia and suggests
      that more frequent dosing of L-dopa plus entacapone may be a useful treatment
      strategy for patients in the early stages of Parkinson's disease.

PMID- 15490462
TI  - Conceptual and perceptual novelty effects in human medial temporal cortex.
AB  - Medial temporal lobe (MTL) structures often respond to stimulus repetition with a
      reduction in neural activity. Such novelty/familiarity responses reflect the
      mnemonic consequences of initial stimulus encounter, although the aspects of
      initial processing that lead to novelty/familiarity responses remain unspecified.
      The current functional magnetic resonance imaging (fMRI) experiment examined the
      sensitivity of MTL to changes in the semantic representations/processes engaged
      across stimulus repetitions. During initial study blocks, words were visually
      presented, and participants made size, shape, or composition judgments about the
      named referents. During repeated study blocks, the initial words were visually re
      presented along with novel words, and participants made size judgments for all
      items. Behaviorally, responses were faster to repeated words in which the same
      task was performed at initial and repeated exposure (i.e., size-->size) relative
      to repeated words in which the tasks differed (i.e., composition-->size and shape
      ->size). fMRI measures revealed activation reductions in left parahippocampal
      cortex following same-task and different-task repetition; numerically, the effect
      was larger in the same-task condition. Accordingly, left parahippocampal cortex
      demonstrates sensitivity to perceptual novelty/familiarity, and it remains
      unclear whether this region also is sensitive to novelty/familiarity in the
      conceptual domain. In left perirhinal cortex, a novelty/familiarity effect was
      observed in the same-task condition but not in the different-task condition, thus
      revealing sensitivity to the degree of semantic overlap across exposures but
      insensitivity to perceptual repetition of the visual word form. Perirhinal
      sensitivity to semantic repetition and insensitivity to perceptual repetition
      suggests that human perirhinal cortex receives conceptual inputs, with perirhinal
      contributions to declarative memory perhaps partially stemming from its role in
      processing semantic aspects of experiences.

PMID- 15490463
TI  - Effect of growth factors on proliferation and phenotypic differentiation of human
      fetal neural stem cells.
AB  - Human fetal neural stem cells (hNSCs) can be expanded in vitro by mitogens or
      growth factors, such as basic fibroblast growth factor (bFGF), epidermal growth
      factor (EGF), and/or leukemia inhibitory factor (LIF). Their effects on
      proliferation rate and differentiation pattern of hNSCs, however, have not been
      fully characterized. In this study, we cultured hNSCs in seven regimens,
      including bFGF, EGF, and LIF, either alone or in combinations. Cells were
      maintained as neurospheres in treatment media for various periods, up to six
      passages. A combination of bFGF, EGF, and LIF expanded hNSCs more efficiently
      than any other treatment as determined by counting total cell numbers using a
      trypan blue exclusion assay, a WST-1 cell viability assay, and a
      bromodeoxyuridine incorporation flow cytometric analysis. Differentiation
      patterns of hNSCs expanded under different conditions were also analyzed. We
      reported previously that hNSCs primed in vitro with a combination of bFGF,
      heparin, and laminin (FHL) induced neuronal differentiation toward a cholinergic
      phenotype. In this study, we show that the FHL priming increases neuronal
      differentiation while decreasing astroglial generation in all treatment groups as
      determined by immunostaining. However, cells proliferated under different growth
      factor conditions do vary in their phenotypic differentiation patterns.
      Particularly, significant generation of cholinergic cells was observed only in
      hNSCs expanded with EGF/bFGF or EGF/bFGF/LIF, but not with other treatment
      regimens, even when they are exposed to the same priming procedure. Our results
      indicate that hNSCs are highly plastic, with their proliferation and
      differentiation potential dependent on different growth factor treatments.

PMID- 15490464
TI  - Analysis and comparison of morphological reconstructions of hippocampal field CA1
      pyramidal cells.
AB  - Morphological reconstructions have become a routine and valuable tool for
      neuroscientists. The accuracy of reconstructions is a matter of considerable
      interest given that they are widely used in computational studies of neural
      function. Despite their wide usage, comparisons of reconstructions obtained using
      various methodologies are lacking. We reviewed reconstructions of hippocampal CA1
      pyramidal cells from five published studies and found marked differences in some
      of the most basic measurements. For four of the five studies means of total cell
      length clustered in the 11,479-13,417-microm range. The remaining study had a
      significantly larger value for this index at 16,992+/-5,788 microm. Surface area
      means varied more than 4-fold from 16,074 to 67,102 microm2. Volume means varied
      more than 8-fold from 3,828 to 30,384 microm3. Simulated passive input resistance
      means varied from 38.0 to 172.1 MOmega, reflecting the variability in cell
      dimensions. Estimates of the electrotonic length varied from 1.26 to 1.56. In two
      reconstructions used in previously published studies, simulated somatic
      excitatory postsynaptic potentials (EPSPs) varied 2-4-fold in amplitude, time to
      peak and half-width, for synaptic inputs at similar locations. Substantial jitter
      on the z-axis was identified as one likely source of the discrepancy in total
      cell length, while substantial differences in diameter measurements across
      studies, and sometimes within the same study, accounted for the variability in
      surface area and volume. While some part of the observed variability is surely
      due to the diversity of CA1 pyramidal cells, our analysis suggests that a
      substantial portion stemmed from methodological inconsistencies and from
      technological limitations. Suggestions are made for improving the quality and
      usefulness of morphological reconstructions. We conclude that reconstructions
      across studies have substantial variability in measures that are very relevant to
      neuronal function. Consequently, modelers are advised to use more than just one
      reconstructed cell in their simulations of neural function.

PMID- 15490465
TI  - Olfactory learning-related NCAM expression is state, time, and location specific
      and is correlated with individual learning capabilities.
AB  - The notion that long-term synaptic plasticity is generated by activity-induced
      molecular modifications is widely accepted. It is well established that neural
      cell adhesion molecule (NCAM) is one of the prominent modulators of synaptic
      plasticity. NCAM can be polysialylated (PSA-NCAM), a reaction that provides it
      with anti-adhesion properties. In this study we have focused on NCAM and on its
      polysialylated state, and their relation to learning of an olfactory
      discrimination task, which depends on both the piriform (olfactory) cortex and
      hippocampus. We trained rats to distinguish between pairs of odors until rule
      learning was achieved, a process that normally lasts 6-8 days. At four time
      points, during training and after training completion, synaptic NCAM and PSA-NCAM
      expression were assessed in the piriform cortex and hippocampus. We report that
      NCAM modulation is specific to PSA-NCAM, which is upregulated in the hippocampus
      one day after training completion. We also report a correlation between the
      performance of individual rats in an early training stage and their NCAM
      expression, both in the piriform cortex and hippocampus. Since individual early
      performance in our odor discrimination task is correlated with the performance
      throughout the training period, we conclude that early NCAM expression is
      associated with odor learning capability. We therefore suggest that early
      synaptic NCAM expression may be one of the factors determining the capability of
      rats to learn.

PMID- 15490466
TI  - Cancer mortality and incidence among a cohort of benzidine and dichlorobenzidine
      dye manufacturing workers.
AB  - BACKGROUND: Benzidine is classified as a definite human carcinogen and
      dichlorobenzidine as a probable human carcinogen. METHODS: A cohort study of 538
      workers potentially exposed to benzidine and/or dichlorobenzidine from a single
      chemical manufacturing facility was conducted. Social Security records were used
      to identify all employees who worked at the facility from 1960 to 1977. Vital
      status was determined through 2001 and cancer incidence through 2002. RESULTS: A
      total of 22 bladder cancer cases were identified. For three individuals, bladder
      cancer was the underlying cause of death. Increased standardized mortality ratios
      (SMRs) were found for all cancer 1.54 (95% CI 1.04-2.19), bladder cancer 8.34
      (95% CI 1.72-24.78), and lymphohematopoietic cancer 2.84 (95% CI 1.04-6.18). The
      standardized incidence ratio (SIR) for bladder cancer was 6.85 (95% CI 4.30
      10.4). Only one case of bladder cancer was identified among the workers who were
      exposed to dichlorobenzidine only. However, an increased risk for
      lymphohematopoietic cancer was found among these dichlorobenzidine only workers
      (SMR 6.62 (95% CI 1.37-19.36)). CONCLUSIONS: This study confirms the high risk of
      bladder cancer among benzidine exposed workers even years after exposure has
      ceased, and raises suggestive evidence of increased risk to lymphohematopoietic
      cancer from exposure to benzidine or dichlorobenzidine.

PMID- 15490467
TI  - Occupational exposures and inpatient hospital care for lumbar intervertebral disc
      disorders among Finns.
AB  - BACKGROUND: Low back disorders are among the most common health problems in
      industrialized societies. We examined the relationship between occupational
      exposures and severe lumbar intervertebral disc disorders (LIDD). METHODS:
      Information on inpatient care for LIDD (ICD-10: M51.1-51.9) in Finnish hospitals
      during 1996 was linked with the 1995 Population Census, and based on occupational
      title with the Finnish Job Exposure Matrix and the Occupational Lifestyle Matrix.
      There were 3,863 individuals hospitalized due to LIDD among occupationally active
      Finns. Poisson regression analyses were made with the total occupationally active
      population as reference. RESULTS: In a multivariate analysis in women, accident
      risk, job control, and three-shift work were associated with hospitalization,
      together with age, education, personal income, and average body mass index (BMI)
      by occupation. In men, accident risk and job control were associated with
      hospital admissions, allowing for age, education, and income. CONCLUSIONS:
      Accident risk and job control increased the risk of hospitalization for LIDD in
      both sexes. Three-shift work and BMI were also predictive of hospital admission
      among women.

PMID- 15490468
TI  - The beryllium lymphocyte proliferation test: Relevant issues in beryllium health
      surveillance.
AB  - BACKGROUND: The beryllium lymphocyte proliferation test (Be-LPT) measures
      beryllium-specific cellular immune response, and is useful in medical
      surveillance of beryllium sensitivity and chronic beryllium disease (CBD).
      METHODS: Current and former employees (n = 12,194) of 18 United States Department
      of Energy (DOE) sites were tested for beryllium sensitization at four
      laboratories with Be-LPT expertise. Beryllium sensitized individuals were offered
      evaluations for CBD. The sensitivity, specificity, and positive predictive value
      (PPV) of the Be-LPT were determined, as was inter- and intra-laboratory
      agreement. RESULTS: False positives were calculated to be 1.09%, with a
      laboratory range of 0.00-3.35% for the 10-year investigation. Be-LPTs performed
      on inter-laboratory split blood specimens from sensitized individuals showed a
      false negative rate of 31.7%. The intra-laboratory repeatability of abnormal Be
      LPT results ranged from 80.4-91.9%. The sensitivity of the Be-LPT was determined
      to be 0.683, with a specificity of 0.969. The PPV of one abnormal Be-LPT was
      0.253. CONCLUSIONS: The Be-LPT is efficacious in medical surveillance of
      beryllium-exposed individuals. The PPV of the Be-LPT is comparable to other
      widely accepted medical tests. Confirmation of an abnormal result is recommended
      to assure appropriate referral for CBD medical evaluation.

PMID- 15490469
TI  - Mechanical resistance of a new biomaterial, ostrich pericardium, and a new method
      of joining tissues combining suturing and a biological adhesive.
AB  - We studied the mechanical behavior in response to tensile stress of samples of
      ostrich pericardium bonded with a cyanoacrylate glue or sewn with a rectangular,
      overlapping suture that was subsequently sealed with the same bioadhesive.
      Seventy-two trials were performed in three series of 24 samples each: series AG,
      glued with an overlap of 1 cm2; series ASG, sewn with a rectangular, overlapping
      suture and sealed; and series AC, control samples that were left intact. The mean
      stress at rupture in series AG (glued) was 0.1 MPa, much lower than the working
      stress of a human valve leaflet, which is approximately 0.25 MPa. In the control
      series, this stress was 26.28 MPa. At rupture in series ASG (sutured/glued), the
      suture material was being subjected to a stress of 64.91 MPa, thus confirming the
      existence of an interaction between the suture and the shear stress exerted by
      the suture on the samples of pericardium. In series ASG, the mean value for the
      resistance to rupture when measured in machine kg was 8.83 kg, lower than but
      similar to that recorded in the control series AC (10.26 kg). The percentages of
      reversible deformation, or elongation, once the samples were torn were similar in
      series AC (19.15%) and ASG (21.93%). This phenomenon can only be explained by the
      damage to the collagen fibers in the area around the rupture, while other more
      distant regions work at a lower load within the elastic limit. We conclude that
      cyanocrylate adhesives alone are not suitable as bonding materials in cardiac
      bioprostheses. The results with the rectangular, overlapping suture, when
      subsequently sealed with an adhesive, can be considered good because, although
      this approach does not impede shear stress, it does maintain an excellent degree
      of resistance to rupture of the samples thus joined. We stress the need to take
      into account the concentration of the load in the design of bioprostheses.

PMID- 15490470
TI  - Worker training for new threats: a proposed framework.
AB  - BACKGROUND: In an effort to identify health and safety training needs for various
      groups of workers related to weapons of mass destruction, including chemical,
      biological, radiological, and nuclear weapons and high yield explosives (CBRNE),
      a conference, "Worker Training in a New Era: Responding to New Threats," was held
      at the Johns Hopkins Bloomberg School of Public Health in October 2002. METHODS:
      Two questions were addressed: Which general skills and knowledge are common to
      all workers who might be exposed to terrorist threats from CBRNE weapons? What
      are the particular skills and knowledge relevant to these threats that are
      specific to workers in different sectors? RESULTS: Thirteen core components for
      pre- and post-event training were identified. Pre-event training applies to all
      workers. Post-event training applies to selected personnel including first
      responders, skilled support personnel, and other workers involved in these
      operations. Recommendations to improve worker safety training related to
      preparedness include: identify specific competencies for worker pre- and post
      event training; coordinate Federal policy on worker training for CBRNE hazards;
      adopt federal guidelines or standards on worker training for new CBRNE threats,
      based on the competencies and coordinated Federal policy; conduct an inventory of
      training programs and other resources that could be used or adapted for use for
      new threats; and develop new training content and methods for pre- and post-event
      training to address specific competencies. CONCLUSIONS: Given the possibility for
      the introduction of CBRNE threats into the workplace, all workers need some
      training in the potential hazards involved: the individual worker's specific role
      in an emergency; incident command; activation of the emergency notification
      system; use of personal protective equipment (PPE); and safe evacuation of the
      workplace. While some occupational sectors have developed effective training
      related to these new threats, there is a need to develop, implement, and evaluate
      training programs across many different sectors of the workforce.

PMID- 15490471
TI  - Hospital response to chemical terrorism: personal protective equipment, training,
      and operations planning.
AB  - BACKGROUND: Hospitals distant from the immediate site of an incident involving a
      hazardous materials (HAZMATs) release which could include chemical warfare
      agents, must develop emergency response plans (ERPs) to protect healthcare
      professionals if they receive potentially contaminated victims. The ERP must
      address OSHA, EPA, and JCAHO requirements. METHODS: The VHA convened groups to
      develop a hazard and exposure assessment, identify actions for compliance with
      existing regulatory standards, and review site and operational planning issues.
      Exposure modeling results were used to derive relationships between operational
      parameters (time and distance from sites/sources) and potential exposure for
      healthcare workers. RESULTS: According to exposure modeling, level C personal
      protective equipment is adequate to protect hospital staff distant from the
      chemical release site. Decontamination runoff and contaminated clothing should
      also be controlled to limit exposure. CONCLUSIONS: Development and coordination
      of ERPs must include the local emergency planning committee, with clear
      assignment of tasks, locations, and training in order to prevent exposures to
      healthcare workers.

PMID- 15490472
TI  - Elbow and wrist/hand symptoms among 6,943 computer operators: a 1-year follow-up
      study (the NUDATA study).
AB  - BACKGROUND: The aim of this study was to examine relations between computer work
      aspects and elbow and wrist/hand pain conditions and disorders. METHODS: In a 1
      year follow-up study among 6,943 technical assistants and machine technicians
      self-reported active mouse and keyboard time, ergonomic exposures and
      associations with elbow and wrist/hand pain were determined. Standardized
      clinical examinations were performed among symptomatic participants at baseline
      and at follow-up. RESULTS: For continuous duration of mouse time adjusted linear
      effects were statistically significant for all investigated pain conditions. For
      continuous duration of keyboard time the corresponding effects were statistically
      significant for wrist/hand pain conditions except incident 'severe' wrist/hand
      pain. There were no threshold effects above 0 hr per week (hr/w) of mouse
      exposure in association with pain conditions, while keyboard exposure showed a
      threshold effect with 12-month wrist/hand pain at follow-up. Clinical diagnoses
      were not associated with exposure. CONCLUSIONS: Detailed examination of self
      reported exposures showed that mouse and keyboard time predicted elbow and
      wrist/hand pain from low exposure levels without a threshold effect, but mouse
      and keyboard time were not predictors of clinical conditions.

PMID- 15490473
TI  - The British approach to asbestos standard setting: 1898-2000.
AB  - BACKGROUND: The asbestos industry started in the late 1870s, and the first
      accounts of severe respiratory disease in its workers were published in England
      (1898, 1906), France (1907), and Italy (1908). For a hundred years, a series of
      increasingly lower standards were set for asbestos in Britain: initially they
      purported to prevent asbestosis, and latterly to reduce asbestosis and
      malignancies to acceptable levels. METHODS: Published accounts of how British
      asbestos exposure standards came to be derived are reviewed in the light of
      archival materials originated by industry and government. RESULTS: The earliest
      standard, of necessity, was not evidence based and while subsequent standards
      purported to relate doses to effects, the indifferent quality of the measurement
      of dose, and the poor discrimination of effects, militated against arriving at a
      standard in which trust should be placed. Each successive standard that was
      accepted, conformed to what could be achieved in production processes, as far as
      it was reasonably practicable on technological and economic grounds. CONCLUSIONS:
      For the better part of a hundred years, confidence was misplaced in the ability
      of process engineers and physicians to protect workers against asbestos. Finally,
      deciding that asbestos was neither technologically nor economically essential,
      and was unsafe in use, Europe issued a Directive, to which Britain will conform,
      that will virtually ban it use throughout the Community by 2006.

PMID- 15490474
TI  - Polyisocyanates in occupational environments: a critical review of exposure
      limits and metrics.
AB  - BACKGROUND: Determination of polyisocyanates is important because they are a
      major contributor of exposure to the isocyanate functional group in many
      workplace environments and are capable of inducing sensitization and asthma.
      However, with multiple different measurement metrics in use, comparison of
      isocyanate exposure data between studies and development of occupational exposure
      limits (OELs) for polyisocyanates is difficult. METHODS: An analysis of existing
      problems in the measurement and regulation of isocyanates is presented based on
      the published analytical, toxicological, and regulatory literature, and the
      authors' own analytical data and experience with isocyanates. RESULTS: This
      analysis supports a need for standardization of isocyanate measurement metrics
      and provides a framework for the development of an OEL for polyisocyanates.
      CONCLUSIONS: The total isocyanate group (microg NCO/m(3)) is recommended as the
      most feasible and practical metric (unit) by which to express polyisocyanate
      exposures for research, control, and regulatory purposes. The establishment of a
      comprehensive isocyanate OEL that simplifies the current agent-by-agent approach
      and expands coverage to polyisocyanates is also recommended.

PMID- 15490475
TI  - Surveillance of occupational noise exposures using OSHA's Integrated Management
      Information System.
AB  - BACKGROUND: Exposure to noise has long been known to cause hearing loss, and is
      an ubiquitous problem in workplaces. Occupational noise exposures for industries
      stored in the Occupational Safety and Health Administration's (OSHA) Integrated
      Management Information System (IMIS) can be used to identify temporal and
      industrial trends of noise exposure to anticipate changes in rates of hearing
      loss. METHODS: The noise records in OSHA's IMIS database for 1979-1999 were
      extracted by major industry division and measurement criteria. The noise
      exposures were summarized by year, industry, and employment size. RESULTS: The
      majority of records are from Manufacturing and Services. Exposures in
      Manufacturing and Services have decreased during the period, except that PEL
      exposures measured by federal enforcement increased from 1995 to 1999.
      CONCLUSIONS: Noise exposures in manufacturing have been reduced since the late
      1970s, except those documented by federal enforcement. Noise exposure data
      outside manufacturing is not well represented in IMIS.

PMID- 15490476
TI  - Healthcare and the long haul: Long distance truck drivers--a medically
      underserved population.
AB  - BACKGROUND: Long distance trucking is associated with significant health risks.
      However, to our knowledge no published data exist regarding healthcare service
      access by the estimated two million long-haul truckers in the United States.
      METHODS: A cross-sectional study was designed to assess access to healthcare
      among these workers. Five hundred-twenty-one anonymous self-administered surveys
      were completed at 16 truck stops in 14 states from July through August 2002.
      RESULTS: Forty-seven percent of those surveyed lack a regular healthcare
      provider, 20% frequent emergency rooms and urgent care centers, 32% were unable
      to receive needed healthcare within the last year, and 56% had difficulty
      utilizing healthcare services at home. Individuals lacking health insurance (31%)
      experienced more difficulty with healthcare access than the insured within the
      last year, were more often without a regular provider (P = 0.002 and P < 0.001),
      and utilized urgent care centers and emergency rooms more often than the insured
      (25 vs. 17%). CONCLUSIONS: Long distance truck drivers are at risk for poor
      health outcomes and experience significant difficulty accessing healthcare
      services. Further studies concerning how to best provide healthcare to this
      vulnerable, underserved population are needed.

PMID- 15490477
TI  - Respiratory findings in pharmaceutical workers.
AB  - BACKGROUND: Pharmaceutical workers may be at risk for the development of
      respiratory problems as a result of their work environment. METHODS: This study
      investigated 163 female and 35 male workers, employed in a pharmaceutical plant
      processing different types of medication, primarily antibiotics, in order to
      characterize the risk of this environment. Chronic respiratory symptoms were
      recorded by using the British Medical Research Council questionnaire. Acute
      symptoms, which developed during the work shift, were also recorded. Ventilatory
      capacity was measured by recording maximum expiratory flow-volume (MEFV) curves
      on which FVC, FEV1, FEF50, and FEF25 were measured. Controls (113) were selected
      from a food packing facility. RESULTS: A significantly higher prevalence of
      chronic respiratory symptoms was recorded among workers (compared to controls),
      the highest being for sinusitis, nasal catarrh, and dyspnea. There was also a
      high prevalence of acute symptoms recorded during the workshift. Odds ratio
      showed that the most significant risk factors for these respiratory findings were
      smoking and length of time worked in the pharmaceutical industry, particularly in
      men. Pulmonary function testing demonstrated significantly decreased measured
      values in comparison to predicted European pulmonary function measurements (P <
      0.01). This was particularly pronounced for FEF50 and FEF25, suggesting
      obstructive changes in smaller airways. CONCLUSIONS: Our data suggest that
      workers employed in the pharmaceutical industry may develop respiratory symptoms
      accompanied by ventilatory impairment.

PMID- 15490478
TI  - Emergency management program operational responses to weapons of mass
      destruction: Veterans Health Administration, 2001-2004.
AB  - BACKGROUND: Despite the recognition of chemical emergencies, terrorist events,
      and ongoing threats, little practical guidance exists for healthcare facilities.
      METHODS: An approach and materials developed by the Veterans Health
      Administration in a five-element program over the last 2 years to enhance the
      existing emergency management program is outlined. Nine steps to the development
      of a comprehensive all-hazards, emergency plan and program, with auditing and
      improvement tools are offered. RESULTS: Cognitive aids for clinical use are
      available on-line and in hard copy. A hazard assessment modeled patients as
      emission sources documenting the operations strategies under which level C
      personal protective equipment will protect healthcare workers. The development of
      this response program appears to support a broader, long-standing VHA approach to
      problem solving. This involves bringing together individual talented field staff,
      representing specific skills, geographic regions, and work styles; investing in
      face-to-face consensus development; and developing programs with extensive
      internal peer-review ("field-based," "bottom-up and top-down," and external
      reviews). CONCLUSIONS: Comprehensive and effective programs can be constructed at
      low cost with reasonable speed within large systems with a public mandate,
      leading to responsible use of public funds internally, and as models for private
      sector programs. It is the long-term operational cost implications, under budget
      constraints in health care, which often present the true challenge.

PMID- 15490479
TI  - Population density regulates Drosophila synaptic morphology in a Fasciclin-II
      dependent manner.
AB  - Genetic analysis of the Drosophila larval neuromuscular junction has identified
      some of the key molecules that regulate synaptic plasticity. Among these
      molecules, the expression level of Fasciclin II (FasII), a homophilic cell
      adhesion molecule, is critically important for determining the final form of the
      neuromuscular junction. Genetic reduction of FasII expression by 50% yields more
      elaborate nerve terminals, while a greater reduction in expression, to 10% of
      wild-type, yields a substantial reduction in the nerve terminal morphology.
      Importantly, regulation of FasII expression seems to be the final output for
      several genetic manipulations that transform NMJ morphology. In an effort to
      understand the importance of this regulatory pathway in the normal animal, we
      have undertaken studies to identify environmental cues that might be important
      for initiating FasII-dependent changes in synaptic plasticity. Here we report on
      the relationship between larval population density and synaptic morphology,
      synaptic strength, and FasII levels. We raised Drosophila larvae under conditions
      of increasing population density and found an inverse exponential relationship
      between population density and the number of synaptic boutons, the number of
      branches, and the length of branches. We also observed population-dependent
      alteration in FasII levels, with lower densities having less FasII at the
      synapse. The correlation between density and morphological change was abrogated
      in larvae constitutively expressing FasII, and in wild-type larvae grown on soft
      culture medium. Together these data show that environmental cues can induce
      regulation of FasII. Interestingly, however, the quantal content of synaptic
      transmission was not different among the different population densities,
      suggesting that other factors contribute to maintaining synaptic strength at a
      defined level.

PMID- 15490480
TI  - Enzymatic stabilization of gelatin-based scaffolds.
AB  - The definitive goal of this research is to develop protein-based scaffolds for
      use in soft tissue regeneration, particularly in the field of dermal healing. The
      premise of this investigation was to characterize the mechanical properties of
      gelatin cross-linked with microbial transglutaminase (mTGase) and to investigate
      the cytocompatibility of mTGase cross-linked gelatin. Dynamic rheological
      analysis revealed a significant increase in the storage modulus and thermal
      stability of gelatin after cross-linking with mTGase. Static, unconfined
      compression tests showed an increase in Young's modulus of gelatin gels after
      mTGase cross-linking. A comparable increase in gel strength was observed with
      0.03% mTGase and 0.25% glutaraldehyde cross-linked gelatin gels. In vitro studies
      using 3T3 fibroblasts indicated cytotoxicity at a concentration of 0.05% mTGase
      after 72 h. However, no significant inhibition of cell proliferation was seen
      with cells grown on lower concentrations of mTGase cross-linked gelatin
      substrates. The mechanical improvement and cytocompatibility of mTGase cross
      linked gelatin suggests mTGase has potential for use in stabilizing gelatin gels
      for tissue-engineering applications.

PMID- 15490482
TI  - Effects of sodium hypochlorite gel and sodium hypochlorite solution on dentin
      bond strength.
AB  - The aim of this study was to determine the effect of 10% NaOCl gel and 10% NaOCl
      solution on dentin bond strengths of four adhesive systems. One hundred eighty
      bovine incisors were ground to achieve a flat polished surface, then divided into
      12 groups: Gluma One Bond [G1-control; G2-NaOCl solution; G3-NaOCl gel]; Prime &
      Bond 2.1 [G4-control; G5-NaOCl solution; G6-NaOCl gel]; Single Bond [G7-control;
      G8-NaOCl solution; G9-NaOCl gel]; Prime & Bond NT [G10-control; G11-NaOCl
      solution; G12-NaOCl gel]. Dentin was etched, rinsed, and blot dried. For the
      experimental groups, after acid etching, 10% NaOCl solution or 10% NaOCl gel was
      applied for 60 s, rinsed, and blot dried. Composite resin was inserted and light
      cured. Shear bond strengths were tested with a crosshead speed of 0.5 mm/min. The
      mean values MPa (SD) were analyzed with two-way ANOVA and Tukey's tests (alpha <
      0.01). Ten percent NaOCl solution significantly increased Gluma One Bond
      strength. No effect was observed for the other adhesives. The 10% NaOCl gel did
      not affect bond strengths. Ten percent NaOCl gel was less effective on collagen
      removal as compared to 10% NaOCl solution. The influence of collagen removal on
      bond strength is dependent on adhesive system, where both the solvent and the
      monomer can influence the results.

PMID- 15490481
TI  - An oxidative stress mechanism mediates chelerythrine-induced heparin-binding EGF
      like growth factor ectodomain shedding.
AB  - Regulated shedding of cell surface proteins is a mechanism for rapid activation
      of autocrine and paracrine signaling. Here we report that chelerythrine, a
      protein kinase C (PKC) inhibitor that possesses a variety of biological
      functions, is a potent inducer of heparin-binding epidermal growth factor-like
      growth factor (HB-EGF) shedding from the cell surface. Chelerythrine induced a
      time- and dose-dependent shedding of an HB-EGF-alkaline phosphatase (HB-EGF-AP)
      fusion protein expressed in MC2 rat prostate epithelial cells. The soluble form
      of HB-EGF-AP bound to heparin and exhibited potent biological activity as
      measured by DNA synthesis assay. Chelerythrine-induced HB-EGF shedding was
      metalloproteinase-(MMP-) mediated because specific MMP antagonists inhibited
      shedding by > or =60%. Chelerythrine stimulated production of reactive oxygen
      species, and antioxidants prevented chelerythrine-induced HB-EGF shedding,
      suggesting that the production of intracellular peroxides is necessary for this
      event. Consistent with this possibility, antioxidant- and MMP-inhibitable
      shedding was also demonstrated when hydrogen peroxide was used as an inducer.
      Although JNK/SAPK and p38 MAPK pathways were activated by chelerythine, these
      signaling mechanisms were not required to mediate the shedding event. However,
      JNK signaling was involved in chelerythrine-stimulated apoptosis. Our results
      suggest that HB-EGF shedding induced by chelerythrine is mediated predominantly
      via the production of reactive oxygen species.

PMID- 15490483
TI  - Acute neuropathy mimicking porphyria induced by aminolevulinic acid during
      photodynamic therapy.
AB  - An 82-year-old man developed severe, acute, predominantly motor polyneuropathy,
      signs of autonomic involvement, and skin changes following aminolevulinic acid
      (ALA) administration. The compound was used as a prodrug for photodynamic therapy
      of Barrett's esophagitis. Changes were observed in various parameters of the heme
      pathway. The case reported represents a rare response to ALA treatment,
      resembling an acute attack of hepatic porphyria with neurological features.

PMID- 15490484
TI  - Fate of constitutive endocytic vesicles formed in the growth cone: transport of
      vesicles from one growth cone to another in the same neuron.
AB  - A developing neuron must have multiple paths of communication coordinating events
      among all its parts. One of these is the transport to the cell body of endocytic
      vesicles formed in growth cones. In order to observe this at single cell
      resolution, we developed a technique in which the fluorescent dye FM1-43 was
      applied to a single growth cone and newly formed constitutive endocytic vesicles
      were labeled. Using low light, time-lapse microscopy we were able to follow the
      movement of these vesicles throughout the neuron. The vast majority of the
      transported vesicles went to the cell body. However, many were observed to enter
      secondary neurites and to be transported to other growth cones. These new, more
      direct paths of transport that link the multiple growth cones of a neuron may
      play a role in several important developmental events involving interactions
      between the multiple neurites of a single neuron.

PMID- 15490485
TI  - Effects of alcohol on skeletal and cardiac muscle.
AB  - The acute and chronic toxic effects of alcohol on skeletal and cardiac muscle are
      clinically important. Muscle weakness and atrophy are the main manifestations of
      skeletal myopathy, and arrhythmias and progressive left-ventricular dysfunction
      are those of cardiomyopathy. Most patients remain asymptomatic from these effects
      for a long time. Myocyte atrophy and death are the main pathological findings. A
      clear dose-related effect has been established with ethanol consumption, with
      gender and some specific gene polymorphisms being factors of increased
      susceptibility to alcohol-induced muscle damage. Pathogenic mechanisms are
      pleiotropic, the most relevant being disturbances in carbohydrate, protein, and
      energy cell turnover, signal transduction, and induction of apoptosis and gene
      dysregulation. Ethanol abstinence is the only effective treatment, although
      controlled drinking is useful in patients who do not achieve abstinence.
      Persistent high-dose consumption results in deterioration of muscle and heart
      function, with a high mortality due to arrhythmias and progression of heart
      failure.

PMID- 15490486
TI  - Changes in voluntary torque and electromyographic activity following oral
      baclofen.
AB  - The consequences of baclofen intake on voluntary motor behaviors remain unclear.
      We studied the effects of single oral doses of baclofen on voluntary, isometric
      knee extension torques and surface and single motor unit (MU) electromyographic
      (EMG) activity from the vastus lateralis in 11 individuals without neurological
      injury. Examination of submaximal to maximal contractions of varying duration
      performed pre- and post-baclofen ingestion revealed significant decreases in
      maximal knee torques and EMG magnitude, accompanied by an increase in slope of
      the torque-EMG relation. A decreased slope of the torque-MU firing rate relation
      was also demonstrated post-baclofen, but without changes in minimal firing rates
      or recruitment forces. During sustained contractions at < or =25% of maximal
      voluntary torque elicited after baclofen ingestion, increased EMG activity was
      observed without significant differences in MU firing rates. Our results
      demonstrate a clear reduction in the maximal torque-generating ability following
      baclofen. Specific changes in MU firing patterns indicate that weakness may be
      due partly to reduced motoneuronal excitability, although use of MU discharge
      patterns to assess these effects is limited in its sensitivity.

PMID- 15490487
TI  - Tumor response and toxicity with multiple infusions of high dose 131I-MIBG for
      refractory neuroblastoma.
AB  - BACKGROUND: (131)I Metaiodobenzylguanidine ((131)I-MIBG) is an effective targeted
      radiotherapeutic for neuroblastoma with response rates greater than 30% in
      refractory disease. Toxicity is mainly limited to myelosuppression. The aim of
      this study was to determine the response rate and hematologic toxicity of
      multiple infusions of (131)I-MIBG. PROCEDURE: Patients received two to four
      infusions of (131)I-MIBG at activity levels of 3-19 mCi/kg per infusion. Criteria
      for subsequent infusions were neutrophil recovery without stem cell support and
      lack of disease progression after the first infusion. RESULTS: Sixty-two
      infusions were administered to 28 patients, with 24 patients receiving two
      infusions, two patients receiving three infusions, and two patients receiving
      four infusions. All patients were heavily pre-treated, including 16 with prior
      myeloablative therapy. Eleven patients (39%) had overall disease response to
      multiple therapies, including eight patients with measurable responses to each of
      two or three infusions, and three with a partial response (PR) after the first
      infusion and stable disease after the second. The main toxicity was
      myelosuppression, with 78% and 82% of patients requiring platelet transfusion
      support after the first and second infusion, respectively, while only 50% had
      grade 4 neutropenia, usually transient. Thirteen patients did not recover
      platelet transfusion independence after their final MIBG infusion; stem cell
      support was given in ten patients. CONCLUSIONS: Multiple therapies with (131)I
      MIBG achieved increasing responses, but hematologic toxicity, especially to
      platelets, was dose limiting. More effective therapy might be given using
      consecutive doses in rapid succession with early stem cell support.

PMID- 15490488
TI  - Pediatric ovarian tumors: a review of 67 cases.
AB  - BACKGROUND: Ovarian tumors are uncommon but important childhood neoplasms.
      PROCEDURE: We reviewed records of 67 pediatric patients presenting to three
      pediatric referral centers from 1980 to 2003. RESULTS: Thirty patients had benign
      tumors. Thirty-seven patients had malignant tumors: 11 immature teratomas, seven
      malignant mixed germ cell tumors, seven juvenile granulosa cell tumors, five
      dysgerminomas, two endodermal sinus tumors, two serous papillary
      cystadenocarcinomas, one small cell carcinoma, one anaplastic sex-cord tumor, and
      one undifferentiated sarcoma. More than half presented with abdominal pain. Forty
      six percent had an abdominal mass at the time of presentation. Other signs and
      symptoms included poor appetite (15%), urinary symptoms/urinary infection (9%),
      menstrual changes (9%), and weight loss (6%). Precocious puberty was noted in
      seven patients. Torsion was seen more often in patients with benign tumors (23
      vs. 8%); two patients had both torsion and acute appendicitis. The neoplasm was
      an incidental finding in 12 patients. CONCLUSIONS: Fifty-five percent of the 67
      ovarian tumors presenting to our centers were malignant. Pain was the most common
      symptom, although presence of an abdominal mass was frequent, and other symptoms
      non-specific. Almost all neoplasms presented as unilateral masses and rarely were
      metastatic at diagnosis. Ovarian tumors must be considered in the differential
      diagnosis of young girls with abdominal pain, mass, or other non-specific
      symptoms.

PMID- 15490489
TI  - Cetirizine from topical phosphatidylcholine liposomes: evaluation of peripheral
      antihistaminic activity and systemic absorption in a rabbit model.
AB  - This study was performed to assess the peripheral H(1)-antihistaminic activity
      and extent of systemic absorption of cetirizine from liposomes applied to the
      skin. Cetirizine was incorporated into small unilamellar vesicles (SUV) and
      multilamellar vesicles (MLV) prepared using L-alpha-phosphatidylcholine, and into
      Glaxal Base (GB), used as the control. In a randomized, cross-over study, each
      formulation, containing 10 mg of cetirizine, was applied to depilated areas on
      the backs of six rabbits (3.08+/-0.05 kg). Histamine-induced wheal tests and
      blood sampling were performed before cetirizine application and at designated
      times for up to 24 h. Compared with the baseline, histamine-induced wheal
      formation was suppressed by cetirizine in SUV and MLV from 0.5-24 h and by
      cetirizine in GB from 0.5-8 h, p</=0.05. Maximum wheal suppression by cetirizine
      in SUV and MLV ranged from 90.6%+/-4.9% to 89.0%+/-3.8% and 98.0%+/-1.3% to
      94.0%+/-2.3%, respectively, from 6 to 8 h. The plasma cetirizine AUC of 201+/
      24.2 ng.h/ml from SUV was lower than from PC-MLV, 334.6+/-65.1 ng.h/ml and from
      GB, 248.3+/-34.6 ng.h/ml. After 24 h, the percent of the cetirizine dose
      remaining on the backs of the rabbits from SUV was lower than from both MLV and
      GB, p</=0.05. In this model, cetirizine from both SUV and MLV had excellent
      topical H(1)-antihistaminic effects, while systemic exposure to cetirizine from
      SUV was reduced.

PMID- 15490490
TI  - Osteosarcoma: is big always worse?

PMID- 15490491
TI  - Increasing value for money in health systems.

PMID- 15490492
TI  - Ethics of embryonic stem cells.

PMID- 15490493
TI  - Ethics of embryonic stem cells.

PMID- 15490494
TI  - Ethics of embryonic stem cells.

PMID- 15490495
TI  - Ethics of embryonic stem cells.

PMID- 15490496
TI  - Ethics of embryonic stem cells.

PMID- 15490497
TI  - Bevacizumab in colorectal cancer.

PMID- 15490498
TI  - Neuropathic diabetic foot ulcers.

PMID- 15490499
TI  - Importance of training and expertise to assess "what works for individuals with
      intellectual disabilities.

PMID- 15490500
TI  - Fiscal year 2003 expenditures for Medicaid long-term services and supports:
      noticeable but limited effects of state budget crisis.

PMID- 15490501
TI  - Ongoing controversy over Romanov remains.

PMID- 15490502
TI  - Ongoing controversy over Romanov remains.

PMID- 15490504
TI  - Growing AIDS problem in Europe.

PMID- 15490505
TI  - IAVI begins trials of AIDS vaccine.

PMID- 15490503
TI  - Pegylated interferon-alpha2a and ribavirin in HIV-hepatitis C coinfected
      patients.

PMID- 15490506
TI  - Brain damage seen in patients on antiretroviral therapy.

PMID- 15490507
TI  - Healthy eating. Fall fruits. The bounty continues.

PMID- 15490508
TI  - Your healthy heart. Making changes. What does it take?

PMID- 15490509
TI  - Hypertension. Management in adults with diabetes.

PMID- 15490510
TI  - Counterfeit drugs. Are you at risk?

PMID- 15490511
TI  - Depression--a different kind of low.

PMID- 15490512
TI  - Reaching for the sunshine. Nothing motivated him; nothing mattered to him until
      Jerry Potts realized that he had sunk into a depression and needed help.

PMID- 15490513
TI  - The hottest diabetes research.

PMID- 15490514
TI  - Chicken any way you like it. Chicken is the perfect choice for a low-carb, low
      fat, high-flavor meal.

PMID- 15490515
TI  - A major advance in the treatment of spinal cord compression.

PMID- 15490517
TI  - Clinical trials report. Asymmetric dimethylarginine, blood pressure, and renal
      perfusion in elderly subjects.

PMID- 15490518
TI  - Leslie Bradley: an appreciation.

PMID- 15490519
TI  - War and demography in twentieth-century Britain.

PMID- 15490520
TI  - Pragmatism, patronage and politics in English biology: the rise and fall of
      economic biology 1904-1920.
AB  - The rise of applied biology was one of the most striking feature of the
      biological sciences in the early 20th century. Strongly oriented toward
      agriculture, this was closely associated with the growth of a number of
      disciplines, notably, entomology and mycology. This period also saw a market
      expansion of the English University system, and biology departments in the newly
      inaugurated civic universities took an early and leading role in the development
      of applied biology through their support of Economic Biology. This sought
      explicitly to promote the application of biological knowledge to economically
      important problems and especially to agriculture. The impact of Economic Biology
      was felt most strongly within Zoology, where it became synonymous with
      entomology. The transience of Economic Biology belies its significance, for
      example, in providing a means for the expansion of biology at the civic
      universities. More broadly, it opened up new research and employment
      opportunities within the life sciences. In late Edwardian Britain, newly
      available state funds for agriculturally relevant biological disciplines
      transformed the life sciences. This paper examines the impact of these funds -
      mobilized either under the 1909 Development Act, or under the auspices of
      colonial interests - on Economic Biology and the institutionalization of applied
      biology. The rise and fall of Economic Biology casts new light on the way in
      which institutional and political alignments profoundly shaped the development of
      British biology.

PMID- 15490521
TI  - X-ray safety in veterinary practice.

PMID- 15490523
TI  - How to balance humane endpoints, scientific data collection and appropriate
      veterinary interventions in animal studies.

PMID- 15490522
TI  - From virus research to molecular biology: Tobacco mosaic virus in Germany, 1936
      1956.
AB  - In 1937, a group of researchers in Nazi Germany began investigating tobacco
      mosaic virus (TMV) with the hope of using the virus as a model system for
      understanding gene behavior in higher organisms. They soon developed a creative
      and interdisciplinary work style and were able to continue their research in the
      postwar era, when they made significant contributions to the history of molecular
      biology. This group is significant for two major reasons. First, it provides an
      example of how researchers were able to produce excellent scientific research in
      the midst of dictatorship and war. Coupled with the group's ongoing success in
      postwar Germany, the German TMV investigators provide a dramatic example of how
      scientific communities deal with adversity as well as rapid political and social
      change. Second, since the researchers focused heavily (though no exclusively) on
      TMV, their story allows us to analyze how an experimental system other than phage
      contributed to the emergence of molecular biology.

PMID- 15490524
TI  - Designing your new animal facility part II: integration of engineering controls
      in animal facility design.

PMID- 15490525
TI  - The architecture of scientific research.

PMID- 15490526
TI  - A behavioural-oriented graded activity program reduced the number of days absent
      from work because of low back pain.

PMID- 15490527
TI  - Taping reduces pain and disability in patients with knee osteoarthritis.

PMID- 15490528
TI  - World will be free of human SARS cases in a few weeks says WHO.

PMID- 15490529
TI  - Awareness campaigns and surveillance systems to prevent further outbreaks of West
      Nile virus.

PMID- 15490530
TI  - Monkeypox confirmed in rodents.

PMID- 15490532
TI  - [No.116: clinico-pathological discussions: fever, anorexia, cardiac murmur and a
      lump on the back].

PMID- 15490531
TI  - Newer bugs causing gastro-intestinal infections.

PMID- 15490533
TI  - Captain Francis Crozier and the last Franklin Expedition.

PMID- 15490534
TI  - Plaques of Sir Alexander Fleming.

PMID- 15490535
TI  - Dr Robert Goodsir.

PMID- 15490536
TI  - Rappaport furrows on our minds: the ASCB Cytokinesis Meeting Burlington, VT July
      22-25, 2004.

PMID- 15490537
TI  - A synthesis of research on effective interventions for building reading fluency
      with elementary students with learning disabilities.
AB  - Fluent reading, often defined as speed and accuracy, is an important skill for
      all readers to develop. Students with learning disabilities (LD) often struggle
      to read fluently, leading to difficulties in reading comprehension. Despite
      recent attention to reading fluency and ways to improve fluency, it is not clear
      which features of interventions that are designed to enhance fluency are
      beneficial for the most struggling readers. The purpose of this study is to
      synthesize research on interventions that are designed primarily to build reading
      fluency for students with LD. The search yielded 24 published and unpublished
      studies that reported findings on intervention features, including repeated
      reading with and without a model, sustained reading, number of repetitions, text
      difficulty, and specific improvement criteria. Our findings suggest that
      effective interventions for building fluency include an explicit model of fluent
      reading, multiple opportunities to repeatedly read familiar text independently
      and with corrective feedback, and established performance criteria for increasing
      text difficulty.

PMID- 15490538
TI  - Exploring hypotheses about phonological awareness, memory, and reading
      achievement.
AB  - Reading-related skills were tested in adults with and without reading
      disabilities (RD) and adults with profound hearing impairment (PHI) who did not
      differ on average Performance IQ. The RD group and the PHI group both
      demonstrated levels of phonological awareness lower than the control group's, but
      only the RD group also exhibited deficits in other skills, including verbal short
      term memory, morphological awareness, speeded written naming, and reading
      comprehension. The average reading level of the PHI group was significantly
      higher than that of the RD group. Three control group members also demonstrated
      limited phonological awareness without other deficits in a pilot study,
      performing similarly to the PHI group. The results support other studies
      suggesting that processes dependent on memory, not solely phonological awareness,
      may contribute to determining reading achievement.

PMID- 15490539
TI  - Separating genuine cases of reading disability from reading deficits caused by
      predominantly inattentive ADHD behavior.
AB  - Conventional methods of differentiating reading disability (RD) caused by
      deficits in decoding skills or comprehension from poor reading performance caused
      by inconsistent attention associated with attention-deficit/hyperactivity
      disorder (ADHD) have produced equivocal results. This study presents a model of
      differential diagnosis of attentional problems and RD that differs from these
      conventional approaches. The new diagnostic procedure uses intraindividual
      differences seen in the performance of at-risk learners on tasks related to
      reading that vary in their sensitivity to the sustained attention required for
      successful performance. The hypothesis is that children with inconsistent
      attention would perform more poorly on tests that require sustained attention,
      such as listening comprehension, than on tests that are more tolerant of
      inattention, such as reading comprehension. Such differences would not be seen in
      the test scores of children who have only RD, because their performance is
      determined more by the difficulty level of the reading tests than by the degree
      of sensitivity of the task to attention. The validity of this new model was
      evaluated by determining the capability of the differences seen in the scores of
      tests that differ in their sensitivity to sustained attention to predict the
      degree of inconsistency in sustained attention as measured by a continuous
      performance test. The data obtained from 39 children who are at risk for RD
      suggest that this is a viable model.

PMID- 15490540
TI  - The use of think-aloud protocols to compare inferencing abilities in average and
      below-average readers.
AB  - In this study, we examined whether think-aloud procedures would uncover
      differences in the kinds of inferences generated by average and below-average
      readers. Participants were 40 third-grade children who were divided into groups
      of average and below-average readers. All participants completed measures of
      nonverbal IQ, reading, language, and working memory, and a story comprehension
      task that consisted of two conditions: listen through and think aloud. The major
      findings in this study were that (a) average readers generated significantly more
      explanatory inferences than below-average readers, and (b) comprehension
      performance as measured by story recall was significantly better for both groups
      in the think-aloud condition than in the listen-through condition. The discussion
      addresses the implications of these findings.

PMID- 15490541
TI  - Information processing deficits in children with attention-deficit/hyperactivity
      disorder, inattentive type, and children with reading disability.
AB  - We examined the information processing capabilities of children diagnosed with
      the inattentive subtype of attention-deficit/hyperactivity disorder (ADHD) who
      had been characterized as having a sluggish cognitive tempo. Children referred
      for school-related problems (n = 81) and nonreferred community controls (n = 149)
      participated. Of the referred children, 24 met criteria for ADHD, 42 met criteria
      for reading disability (RD), and 9 of these were comorbid for RD and ADHD.
      Children with ADHD differed from those without ADHD on a visual search task but
      not on an auditory processing task; the reverse was true for children with RD.
      Decomposition of the visual search task into component operations demonstrated
      that children in the ADHD group had a slow processing rate that was not
      attributable to inattention. The children with ADHD were not globally poor at
      information processing or inattentive, but they demonstrated diminished speed of
      visual processing.

PMID- 15490542
TI  - The transition from high school to postsecondary education for students with
      learning disabilities: a survey of college service coordinators.
AB  - Federal legislation requires that students with disabilities receive services to
      assist them in the transition from high school to post-secondary life. Transition
      services must address students' understanding of their disability, learning
      strengths and weaknesses, career decision-making skills, and preparation for the
      increased demands of postsecondary education. This study surveyed coordinators of
      special services for students with disabilities at 74 colleges and universities
      in New York state. Respondents provided their perceptions of how well the
      students they served had been prepared by the transition services they had
      received in high school. Overall, little satisfaction with transition services
      was expressed. Respondents were most satisfied with high schools' provision of
      updated evaluations for students prior to enrollment in college, and they rated
      students' preparation for self-advocacy as the greatest weakness of current
      transition services.

PMID- 15490543
TI  - IDEA and collaboration: a Bakhtinian perspective on parent and professional
      discourse.
AB  - In accordance with the Bakhtinian framework of this article, the text represents
      a dialogue between practices documented in the literature; the first author's
      perspective as a teacher, evaluator, and consultant; Bakhtin's theories of
      language; and the lived experiences of the second author, a parent whose child
      has been labeled as having a language learning disability. Although the
      Individuals with Disabilities Education Act (IDEA) grants parents the right to be
      involved in educational decisions about their children, we argue that the routine
      disqualification of parents' voices by school professionals is a major obstacle
      to authentic collaboration. Bakhtin's theories of language serve to illuminate
      the discourse between parents and professionals in special education committee
      meetings. We conclude with our vision for a mutual dialogic exchange between
      parents and professionals.

PMID- 15490544
TI  - Maintenance of certification in the United States: a progress report.
AB  - The American Board of Medical Specialties (ABMS) is working closely with its 24
      member boards to implement the four components of a Maintenance of Certification
      (MOC) program. Those components include evidence of professional standing,
      lifelong learning and self-assessment, cognitive expertise, and evaluation of
      performance in practice. The new MOC program of the ABMS represents a dramatic
      shift from how graduate medical education, initial certification in the medical
      specialties, and recertification in the medical specialties are being conducted.
      This article updates how specialty boards are implementing the four components.

PMID- 15490545
TI  - A new metric for continuing medical education credit.
AB  - The two major continuing medical education (CME) credit systems for allopathic
      physicians in the United States are administered by the American Medical
      Association (AMA) and the American Academy of Family Physicians (AAFP). This
      article explores the history of AMA and AAFP CME credit and its value to
      physicians and the patients they serve. Historically, CME credit has been awarded
      as hours for participation, but this approach is inadequate as a measure of CME
      and its impact on improving physician practice. New credit systems are needed to
      measure a CME activity by its value in bettering the physician's knowledge base,
      competence, and performance in practice.

PMID- 15490546
TI  - Hidden curriculum in continuing medical education.
AB  - In developing curricula for undergraduate and graduate medical education,
      educators have become increasingly aware of an interweaving of the formal,
      informal, and hidden curricula and their influences on the outcomes of teaching
      and learning. But, to date, there is little in the literature about the hidden
      curriculum of medical practice, which takes place after graduation and
      certification. This article initiates that discussion with influences of the
      hidden curriculum on the actions physicians take or do not take in caring for
      patients. Hafferty's framework of institutional policies, evaluation activities,
      resource-allocation decisions, and institutional slang, along with our knowledge
      of health services research and the continuing medical education (CME) research
      literature, suggests that there is a hidden and powerful curriculum that affects
      physician performance. Determining whether the hidden curriculum conflicts with
      the messages that we are delivering through formal CME (courses, clinical
      practice guidelines, peer review journals) may contribute to improving our impact
      on physician performance.

PMID- 15490547
TI  - Commitment to change instrument enhances program planning, implementation, and
      evaluation.
AB  - INTRODUCTION: This study investigates the use of a commitment to change (CTC)
      instrument as an integral approach to continuing medical education (CME)
      planning, implementation, and evaluation and as a means of facilitating physician
      behavior change. METHODS: Descriptive statistics and grounded theory methods were
      employed. Data were collected from 20 consecutive CME programs. Physicians were
      asked to list up to three things they intended to change in their clinical
      practice as a result of the program. A copy was sent 3 weeks later as a reminder.
      Six months later, a summary of peer-intended changes was sent to reinforce
      intended behavior change. RESULTS: Of 602 participants, 291 (48%) completed CTC
      forms, resulting in 803 citations. Responses were congruent with the educational
      objectives and intentions of the program planners. Using the constant comparative
      method of analysis, a framework was identified for interpreting physician
      learning strategies. It included change strategies and motivation, learning
      issues, better doctoring, changes to clinic practice, and diffusion. DISCUSSION:
      CTC was useful as a multipurpose tool providing planners with meaningful feedback
      to (1) assess congruence of intended changes in physician behavior with program
      objectives, (2) document unanticipated learning outcomes, and (3) enable and
      reinforce intended behavior change.

PMID- 15490548
TI  - Barriers facing physicians practicing evidence-based medicine in Saudi Arabia.
AB  - INTRODUCTION: Tremendous advances in health care have been made through the
      development of evidence-based medicine (EBM). Studies show that physicians face
      barriers in practice, preventing the effective use of the best evidence
      available. Insight into these barriers should pave the way for an action plan to
      remove them. The aim of this study was to explore the major barriers to the
      practice of EBM by physicians in primary health care centers (PHCCs) and
      hospitals. METHOD: This cross-sectional study was conducted on physicians in
      PHCCs and Ministry of Health hospitals in the Dammam area (Dammam, Alkhobar, and
      Alqatief) of Saudi Arabia. A sample size of 409 physicians was chosen. Barriers
      to the practice of EBM and the reasons for not giving patients effective health
      care were investigated through questionnaires. RESULTS: The response rate was 66.
      7%. The main barriers to practicing EBM stated by physicians were the lack of
      training in EBM (72.9%), facilities (34.4%), and time (29.2%). The least
      mentioned barriers were the lack of relevant evidence and the negative impact on
      medical skills (10.4% each). DISCUSSION: Rather than skepticism about the
      concept, the main barriers to the use of EBM by physicians appeared to be a lack
      of knowledge and basic skills. Therefore, targeted education in EBM and a system
      that quickly delivers high-quality evidence are needed. This includes the
      allocation of an adequate infrastructure and time and the availability of
      relevant evidence.

PMID- 15490549
TI  - Internet continuing education for health care professionals: an integrative
      review.
AB  - INTRODUCTION: The objective was to review key articles and research studies on
      practices, preferences, and evaluation of on-line continuing education used by
      health care professionals. METHODS: Data sources included searches of the
      MEDLINE, CINAHL, and ERIC databases (January 1990 to June 2004) and manual
      searches of the Journal of Continuing Education in the Health Professions and the
      Journal of Continuing Education in Nursing. Articles included reviews and
      research studies focusing on the use of Internet CE by health care professionals.
      The articles were categorized according to intervention, subjects, study design,
      and key findings. RESULTS: Seventeen articles were eligible and were reviewed.
      Although in-person CE remains the most frequent and most preferred format,
      Internet CE is gaining in popularity. Most participants who engage in on-line CE
      are satisfied with the experience and find it to be an effective learning format.
      Barriers to on-line CE include technical difficulties and lack of computer
      knowledge. DISCUSSION: Although the Internet is an effective and satisfactory
      educational format, barriers to use of the Internet for CE still exist.
      Additional studies are needed to measure the impact of Internet CE on practice
      performance, reduce barriers to on-line CE, and identify appropriate theoretical
      frameworks for on-line learning.

PMID- 15490550
TI  - An academic writing needs assessment of English-as-a-second-language clinical
      investigators.
AB  - INTRODUCTION: Academic writing for publication is competitive and demanding for
      researchers. For the novice English-as-a-second-language (ESL) researcher, the
      pressure to publish compounds the difficulties of mastering the English language.
      Very few studies have used ESL graduate and post-graduate students as academic
      writing research subjects. The purpose of this project was to assess the learning
      needs of ESL clinical investigators regarding academic writing for English
      scholarly publication. METHOD: A qualitative evaluation approach was used to
      examine the gap between the current and desired proficiency level for the
      academic writing of ESL clinical investigators. We considered the perspectives of
      seven ESL clinical investigators plus three mentors and three writing
      instructors. Semi-structured questions were asked. Field notes were organized
      using a field-work recording system. They were analyzed using the constant
      comparative method. RESULTS: ESL clinical investigators do not accurately
      perceive their writing deficiencies. They have little knowledge of criteria for
      academic writing and they are influenced by their prior English learning
      experiences in their home culture, which engender passive attitudes toward
      seeking appropriate writing resources. Adequate time is especially needed to
      develop successful writing skills. DISCUSSION: Four basic steps are recommended
      to guide program planners in developing ESL writing activities for professional
      learning: (1) recognize discrepancies, (2) establish clear standards and
      performance criteria for scholarly writing, (3) develop individual plans, and (4)
      organize long-term writing assistance.

PMID- 15490551
TI  - Rhodovarius lipocyclicus gen. nov. sp. nov., a new genus of the alpha-1 subclass
      of the Proteobacteria.
AB  - A bacterial strain (CCUG 44693T) was recovered during an industrial hygiene
      control. Phylogenetic analyses using the 16S rRNA gene sequence of the isolate
      indicated that it represents a new lineage in the alpha-1 subclass of the
      Proteobacteria, with the highest sequence similarity of 93.3% to the type strain
      of Muricoccus roseus. In the polyamine pattern spermidine was the predominant
      compound. The polar lipid profile consisted of the major lipids phosphatidyl
      ethanolamine, phosphatidyl dimethylethanolamine, phosphatidyl glycerol,
      phosphatidyl cholin and an unknown amino lipid. The major respiratory quinone was
      a ubiquinone Q-10 and the major whole cell fatty acids were 19:0 cyclo omega8c
      and 18:1 omega7c. The isolate also contained 18:1 2-OH and other fatty acids
      typical for members of the alpha-1 subclass of the Proteobacteria in addition to
      10:0 2-OH in low amounts, not detected in members of closely related genera. The
      strain grew heterotrophically and strictly aerobically and formed red-colored
      colonies on tryptone soy agar. Bacteriochlorophyll a could not be detected by
      direct spectrophotometric analyses of aerobically grown cells. On the basis of
      the phylogenetic analyses, chemotaxonomic and biochemical characteristics, we
      propose that strain CCUG 44693T (CIP 108310T) represents a new genus of the alpha
      1 subclass of the Proteobacteria for which we propose the name Rhodovarius
      lipocyclicus gen. nov. sp. nov.

PMID- 15490552
TI  - Polyphasic characterisation of Burkholderia cepacia-like isolates leading to the
      emended description of Burkholderia pyrrocinia.
AB  - Twenty-five Burkholderia cepacia-like isolates of human and environmental origin,
      comprising five different recA RFLP types, were examined by using a polyphasic
      taxonomic approach, including recA gene sequence analysis, 16S rRNA gene sequence
      analysis, DNA:DNA hybridisation studies, tDNA-PCR, fatty acid analysis and
      biochemical analysis. The results of the present study demonstrated that twenty
      three of these strains belong to Burkholderia pyrrocinia, a B. cepacia complex
      species thus far comprising one single soil isolate only. An emended description
      of Burkholderia pyrrocinia is proposed. The taxonomic status of the remaining two
      isolates requires further analysis.

PMID- 15490553
TI  - Vibrio neonatus sp. nov. and Vibrio ezurae sp. nov. isolated from the gut of
      Japanese abalones.
AB  - Five alginolytic, facultative anaerobic, non-motile bacteria were isolated from
      the gut of Japanese abalones (Haliotis discus discus, H. diversicolor
      diversicolor and H. diversicolor aquatilis). Phylogenetic analyses based on 16S
      rRNA gene and gap gene sequences indicated that these strains are closely related
      to V. halioticoli. DNA-DNA hybridizations, FAFLP fingerprintings, and phylogenies
      of gap and 16S rRNA gene sequences showed that the five strains represent two
      species different from all currently described vibrios. The names Vibrio neonatus
      sp. nov. (IAM 15060T = LMG 19973T = HDD3-1T; mol% G+C of DNA is 42.1-43.9), and
      Vibrio ezurae sp. nov. (IAM 15061T = LMG 19970T = HDS1-1T; mol% G+C of DNA is
      43.6-44.8) are proposed to encompass these new taxa. The two new species can be
      differentiated from V. halioticoli on the basis of several features, including
      beta-galactosidase activity, assimilation of glycerol, D-mannose and D-gluconate.

PMID- 15490554
TI  - Vibrio ponticus sp. nov., a neighbour of V fluvialis-V. furnissii clade, isolated
      from gilthead sea bream, mussels and seawater.
AB  - A new Vibrio species, Vibrio ponticus, is proposed to accommodate four marine
      bacteria isolated from sea water, mussels and diseased sea bream (Sparus aurata),
      at the Mediterranean coast of Spain. Strains are Gram negative, slightly
      halophilic bacteria that require Na+ ion for growth, oxidase and catalase
      positive, negative for arginine dihydrolase and ornithine decarboxylase but
      positive for lysine decarboxylase and indole, and utilize beta-hydroxybutyrate as
      a sole carbon source. Phylogenetic analysis locate these marine bacteria in the
      vicinity of the V. fluvialis-V. furnissii clade, sharing with these two species
      16S rDNA sequence similarities slightly above 97% (97.1 and 97.3%, respectively).
      DNA-DNA hybridisation values confirm that the four strains form a genospecies and
      represent a new species in the genus Vibrio. We propose strain 369T (CECT 5869T,
      DSM 16217T) as the type strain.

PMID- 15490556
TI  - Restriction fragment length polymorphism of 16S-23S rDNA intergenic spacer of
      Aeromonas spp.
AB  - We analyzed restriction fragment length polymorphism (RFLP) of 16S-23S rDNA
      intergenic spacer region (ISR) of Aeromonas species. A total of 69 isolates
      belonging to 18 DNA hybridization groups (HG; equivalent of genomic species) were
      used in this study. ISRs were amplified by PCR and the products were digested
      with four restriction endonucleases: Hin6I, Csp6I, TaqI, and TasI. The RFLP
      patterns obtained after digesting by particular enzymes revealed ISR polymorphism
      of isolates allocated to individual genomic species. The combined Hin6I, Csp6I,
      TaqI, and TasI restriction profiles were examined by Dice coefficient (SD) and
      unweighted pair group method of clustering (UPGMA). The isolates were allocated
      into 15 groups, three strains were unclustered. The strains belonging to the
      following genomic species: A. hydrophila, A. bestiarum, A. salmonicida, A.
      caviae, A. media, A. schubertii, A. allosaccharophila, A. popoffii, and A.
      culicicola formed distinct clusters. Strains belonging to HG 6, HG 7, HG 11, and
      HG 16 revealed similar combined RFLP patterns and constituted one group.
      Similarly, the strains of A. jandaei (HG 9) and the type strain of A. trota were
      allocated into one cluster. Two isolates of HG 14 formed distinct cluster. We
      noticed a genetic diversity among A. veronii isolates, the strains were clustered
      in two groups. Our study showed that combined ISR-RFLP analysis may be used for
      identification of some species of Aeromonas.

PMID- 15490555
TI  - Isolation of sulfate-reducing bacteria from the terrestrial deep subsurface and
      description of Desulfovibrio cavernae sp. nov.
AB  - Deep subsurface sandstones in the area of Berlin (Germany) located 600 to 1060 m
      below the surface were examined for the presence of viable microorganisms. The in
      situ temperatures at the sampling sites ranged from 37 to 45 degrees C.
      Investigations focussed on sulfate-reducing bacteria able to grow on methanol and
      triethylene glycol, which are added as chemicals to facilitate the long-term
      underground storage of natural gas. Seven strains were isolated from porewater
      brines in the porous sandstone. Three of them were obtained with methanol
      (strains H1M, H3M, and B1M), three strains with triethylene glycol (strains H1T,
      B1T, and B2T) and one strain with a mixture of lactate, acetate and butyrate
      (strain H1-13). Due to phenotypic properties six isolates could be identified as
      members of the genus Desulfovibrio, and strain B2T as a Desulfotomaculum. The
      salt tolerance and temperature range for growth indicated that the isolates
      originated from the indigenous deep subsurface sandstones. They grew in mineral
      media reflecting the in situ ionic composition of the different brines, which
      contained 1.5 to 190 g NaCl x l(-1) and high calcium and magnesium
      concentrations. The Desulfovibrio strains grew at temperatures between 20 and 50
      degrees C, while the Desulfotomaculum strain was thermophilic and grew between 30
      and 65 degrees C. The strains utilized a broad spectrum of electron donors and
      acceptors. They grew with carbon compounds like lactate, pyruvate, formate, n
      alcohols (C1-C5), glycerol, ethylene glycol, malate, succinate, and fumarate.
      Some strains even utilized glucose as electron donor and carbon source. All
      strains were able to use sulfate, sulfite and nitrate as electron acceptors.
      Additionally, three Desulfovibrio strains reduced manganese oxide, the
      Desulfotomaculum strain reduced manganese oxide, iron oxide, and elemental
      sulfur. The 16S rRNA analysis revealed that the isolates belong to three
      different species. The strains H1T, H3M and B1M could be identified as
      Desulfovibrio indonesiensis, and strain B2T as Desulfotomaculum geothermicum. The
      other Desulfovibrio strains (H1M, H1-13, and B1T) showed identical 16S rDNA
      sequences and similarities as low as 93% to their closest relative, Desulfovibrio
      aminophilusT. Therefore, these isolates were assigned to a new species,
      Desulfovibrio cavernae sp. nov., with strain H1M as the type strain.

PMID- 15490557
TI  - Two new ballistoconidium-forming yeast species, Bullera melastomae and Bullera
      formosana, found in Taiwan.
AB  - Two yeast strains, the cells of which contained xylose and Q-10 as the major
      ubiquinone, were isolated from a plant leaf collected in Taiwan. These yeasts
      were found to represent two new species of the genus Bullera in the
      Hymenomycetes. Identification was based on the sequence analysis of the 18S rDNA,
      the internal transcribed spacer (ITS) regions and the D1/D2 domain of 26S rDNA.
      The yeasts are named Bullera melastomae sp. nov. and Bullera formosana sp. nov.
      In the phylogenetic trees based on 18S rDNA and D1/D2 domain of 26S rDNA
      sequences, these two species constitute a cluster connected with Dioszegia
      cluster in the Cryptococcus luteolus lineage.

PMID- 15490558
TI  - The effect of nucleobase-specific fluorescence quenching on in situ hybridization
      with rRNA-targeted oligonucleotide probes.
AB  - Oligonucleotide probes labeled with fluorescent dyes are used in a variety of in
      situ applications to detect specific DNA or RNA molecules. It has been described
      that probe fluorescence might be quenched upon hybridization in a sequence
      specific way. Here, a set of 17 oligonuleotides labeled with 6-carboxyfluorescein
      was used to examine the relevance of nucleotide specific quenching for
      fluorescence in situ hybridization (FISH) to whole fixed bacterial cells. Probes
      quenched upon hybridization to a guanine-rich region of purified RNA in solution
      were not quenched upon FISH. Among other factors the high protein concentration
      within cells may prevent quenching of probe fluorescence in situ.

PMID- 15490559
TI  - Comparative sequence analysis and oligonucleotide probe design based on 23S rRNA
      genes of Alphaproteobacteria from North Sea bacterioplankton.
AB  - Almost complete 23S rRNA gene sequences were obtained from 11 Alphaproteobacteria
      isolated from marine surface water of the German Bight. Five of the strains
      belong to the "marine alpha" group, a phylogenetic cluster which encompasses
      members of the genus Roseobacter and closely related bacteria. Phylogenetic
      sequence analysis based on 52 published as well as unpublished complete 23S rDNA
      sequences from Alphaproteobacteria including the newly obtained was in general
      consistent with the 16S rRNA gene sequence-derived phylogeny. 16S and 23S rRNA
      based phylogenies both showed a distinct cluster for strains associated with the
      "marine alpha" group. The suitability of both markers for the design of
      oligonucleotide probes targeting selected groups of Alphaproteobacteria was
      systematically evaluated and compared in silico. Six clusters of sequences
      covering different phylogenetic levels as well as two strains were selected in a
      case study. To compensate for the quantitative difference in the two data sets,
      the 16S rRNA dataset was truncated to sequences with an equivalent in the 23S
      rRNA data set. Our results show, that the overall number of phylogenetically
      redundant probes available could be more than doubled by extending probe design
      to the 23S rRNA. For small clusters of high sequence similarity and single
      strains, up to 8 times more discriminating binding sites were provided by the 23S
      rRNA.

PMID- 15490560
TI  - In silico evaluation of molecular probes for detection and identification of
      Ralstonia solanacearum and Clavibacter michiganensis subsp. sepedonicus.
AB  - Ralstonia solanacerum and Clavibacter michiganensis subsp. sepedonicus are the
      two most relevant bacterial pathogens of potato for which a large number of
      molecular diagnostic methods using specific DNA sequences have been developed.
      About one hundred oligonucleotides have been described and thoroughly tested
      experimentally. After having compiled and evaluated all these primers and probes
      in silico to check their specificity, many discrepancies were found. A detailed
      analysis permitted the recognition of different possible reasons for such
      discrepancies: sequencing errors in public sequences, wrong supposed specificity
      (sometimes due to more recent sequences than the oligonucleotides being
      evaluated) or even typing errors in the oligonucleotides. Although this study is
      an exercise about in silico evaluation using two potato bacterial pathogens as a
      model, the conclusions reflect not only information useful for phytopathologists
      but, in a broader scope, draw the main situations that can be found during an
      evaluation of probes, which can be surely found in other scenarios.

PMID- 15490561
TI  - Distribution of microcystin-producing and non-microcystin-producing Microcystis
      sp. in European freshwater bodies: detection of microcystins and microcystin
      genes in individual colonies.
AB  - Microcystis is a well-known cyanobacterial genus frequently producing
      hepatotoxins named microcystins. Toxin production is encoded by microcystin genes
      (mcy). This study aims (i) to relate the mcy occurrence in individual colonies to
      the presence of microcystin, (ii) to assess whether morphological characteristics
      (morphospecies) are related to the occurrence of mcy genes, and (iii) to test
      whether there are geographical variations in morphospecies specificity and
      abundance of mcy genes. Individual colonies of nine different European countries
      were analysed by (1) morphological characteristics, (2) PCR to amplify a gene
      region within mcyA and mcyB indicative for microcystin biosynthesis, (3) matrix
      assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF
      MS) to detect microcystins. Almost one hundred percent of the colonies predicted
      to produce microcystins by PCR analysis were found to contain microcystins. A
      high similarity in microcystin variants in the different colonies selected from
      lakes across Europe was demonstrated. The different morphospecies varied in the
      frequency with which they contained mcy genes. Most colonies (>75%) of M.
      aeruginosa and M. botrys contained the mcy genes, whereas < or = 20% of the
      colonies identified as M. ichthyoblabe and M. viridis gave a PCR product of the
      mcy genes. No colonies of M. wesenbergii gave a PCR product of either mcy gene.
      In addition, a positive relationship was found between the size of the colony and
      the frequency of those containing the mcy genes. It is concluded that the
      analysis of morphospecies is indicative for microcystin production, although the
      quantitative analysis of microcystin concentrations in water remains
      indispensable for hazard control.

PMID- 15490562
TI  - Metabolic and genomic diversity of rhizobia isolated from field standing native
      and exotic woody legumes in southern Ethiopia.
AB  - Eighty-seven rhizobial strains isolated from root nodules of field standing
      native and exotic woody legumes in southern Ethiopia were characterized using the
      Biolog method and AFLP fingerprinting technique. Cluster analysis of the
      metabolic and genomic fingerprints revealed 18 and 25 groups, respectively,
      demonstrating considerable diversity in rhizobial population indigenous to
      Ethiopian soils. While 25 strains (29%) were linked to members of Agrobacterium,
      Bradyrhizobium, Mesorhizobium, Rhizobium or Sinorhizobium, the bulk of the
      strains formed several distinct groups in both methods and did not relate to
      reference species included in the study. In contrast to exotic species which
      formed symbiosis with strains of only one specific genomic group, indigenous host
      species nodulated by metabolically and genomically diverse groups. The results in
      this study support the view, that long-term association between the symbionts
      allows gradual differentiation and diversity in compatible rhizobial population
      resident in native soils. Lack of significant metabolic and genomic relatedness
      to the reference strains in our results suggested that test strains in our
      collection probably included 'unique' types, which belong to several yet
      undefined rhizobial species.

PMID- 15490563
TI  - Molecular characterisation of bacterial contamination in semi-final gelatine
      extracts, using denaturing gradient gel electrophoresis.
AB  - Contamination of gelatine may affect the safety and/or quality of its
      applications. Characterisation of bacterial isolates from semi-final gelatine
      batches revealed thermotolerant, aerobic, endosporeforming contaminants. In this
      paper, bacterial contamination in gelatine batches is analysed without previous
      isolation, by means of denaturing gradient gel electrophoresis (DGGE) of PCR
      amplified 16S rDNA sequences. V9 and V6-V8 regions of the 16S rDNA gene were
      found more suitable for this purpose than V1 or V3 regions. Bacillus fumarioli,
      Bacillus licheniformis, members of the 'Bacillus cereus group', Bacillus
      subtilis, Bacillus shackletonii, Brevibacillus borstelensis and Brevibacillus
      agri were detected.

PMID- 15490564
TI  - Possible involvement of nitric oxide and peroxynitrite in nasal polyposis.
AB  - BACKGROUND: Nitric oxide (NO) is implicated in inflammation. Its role in the
      pathogenesis of nasal polyposis is not clear. METHODS: The expression of
      inducible NO synthase (iNOS), and the production of peroxynitrite represented by
      the formation of 3-nitrotyrosine (3-NT) were examined by immunohistochemistry in
      nasal polyps. The contents of superoxide dismutases (SODs) in nasal polyps and
      nasal mucosa were assessed by Western blot analyses. RESULTS: iNOS expression and
      3-NT accumulation were noted in mucosal epithelium, vascular endothelium, and
      interstitial cells of nasal polyps. In comparison with our previous study on the
      nasal mucosa from patients with rhinitis, the stromal cells of the nasal polyp
      had higher labeling intensity for both iNOS and 3-NT. The polyp showed similar
      levels of CuZnSOD and MnSOD as those of nasal mucosa. CONCLUSIONS: The iNOS/NO
      system may be important in the pathophysiology of nasal polyposis. The increased
      peroxynitrite may result from increased iNOS expression but is not related to
      decreased SODs.

PMID- 15490565
TI  - Evaluation of telomerase activity in nasal polyps.
AB  - BACKGROUND: The objective of this study was to assess if nasal polyps express
      telomerase activity and whether a difference could be found between the polyp and
      the surrounding mucosa of the middle meatus and between different portions of the
      polyp itself METHODS: Nine patients affected by nasal polyposis were included in
      this study; four of these patients had recurring polyposis. Telomerase activity
      was measured by telomeric repeat amplification protocol assay. In six patients,
      the telomeric repeat amplification protocol assay was performed on the polyp and
      on the mucosa from the ipsilateral middle meatus. In a polyp, we were able to
      investigate telomerase activity of its different portions, corresponding to
      pedicle and fundus. RESULTS: Telomerase activity observed in nasal polyps was
      higher than that observed in samples from the ipsilateral middle meatus mucosa.
      High or intermediate telomerase activity was found to be related to predominant
      recurring polyposis. CONCLUSIONS: Therefore, it could be postulated that
      telomerase activity could be related with the tendency of polyps to recur.

PMID- 15490566
TI  - Software-enabled computed tomography analysis of the carotid artery and sphenoid
      sinus pneumatization patterns.
AB  - BACKGROUND: The critical relationship of the carotid artery with the sphenoid
      sinus has been long established. Sophisticated imaging software in conjunction
      with three-dimensional high-resolution computed tomography (CT) imaging now
      facilitates detailed analysis of these anatomic relationships. METHODS: Siemens
      VolumeZoom CT scanner was used to obtain high-resolution computed tomography data
      that was subsequently transferred to the CBYON Suite Doctor Station version 2.6
      for analysis. Various surgical planning tools were used for evaluating the CT
      scans. The relationship of the carotid artery with the sphenoid sinus was
      delineated. RESULTS: One-hundred twenty-eight sides in 64 cadaveric specimens
      were reviewed. Pneumatization of the sphenoid sinus was classified into four
      categories: conchal, presellar, sellar, and postsellar. The incidence of these
      four types was 4.7, 4.7, 25, and 65%, respectively. Carotid artery exposure was
      categorized as follows: no exposure, <90 degrees, >90 to <180 degrees, and >180
      degrees. The incidence of the carotid exposure was 12.5, 32.8, 50, and 4.7%,
      respectively. Septal insertions onto the carotid artery were noted in 37.5% and
      dehiscences in 19.5% of the specimens. CONCLUSION: Computer-aided CT analysis
      allows for a detailed study of the critical relationship of sphenoid
      pneumatization and carotid artery position. Such technology can be invaluable in
      surgical planning and navigation during endoscopic sinus surgery. In lieu of
      these findings, sinus surgeons must exercise extreme caution when operating in
      this region to prevent unintentional injury to the carotid artery.

PMID- 15490567
TI  - Midline necrotizing nasal lesions: analysis of 18 cases emphasizing radiological
      and serological findings with algorithms for diagnosis and management.
AB  - BACKGROUND: The aim of this study was to assess the principal signs and symptoms
      for severe necrotizing midline nasal lesions and give diagnostic and management
      algorithms. METHODS: Literature review and retrospective chart review were
      performed. Three patients with Wegener's granulomatosis (WG), six patients with
      sarcoid, eight patients with cocaine abuse, and one lymphoma patient were
      analyzed with respect to symptom complexes, laboratory results, and radiographic
      findings. Based on computed tomography findings, a nasal destruction score was
      tabulated for each patient. RESULTS: All diseases essentially had similar signs
      and symptoms within the head and neck but several extranasal sites were
      suggestive of specific etiologies. Serological laboratory testing was diagnostic
      in only two of the six sarcoid patients and two of the three WG patients. There
      were no specific tests associated with lymphoma or cocaine abuse, although
      erythrocyte sedimentation rate was consistently and significantly elevated in the
      latter group. Biopsy confirmed disease was found in one of the three sarcoid
      patients, in one of the three WG patients, and in one out of one of the lymphoma
      patients. Nasal destruction scores were highest in WG and lymphoma patients,
      intermediate in cocaine abuse patients, and lowest in patients with sarcoidosis.
      Two of the three WG patients had extensive neoosteogenesis. One out of one
      lymphoma and five of the eight cocaine abuse patients had oronasal or oroantral
      fistulas. CONCLUSION: Laboratory tests and biopsies were consistently unreliable
      in all diseases. Repeat studies should be performed in all cases of negative
      results if clinical suspicion is high. Neo-osteogenesis and mastoid disease were
      associated with WG when compared with patients with similar levels of nasal
      destruction due to other etiologies. Laryngeal and dermatologic changes without
      significant nasal bony abnormalities raised suspicion for sarcoidosis. Hard and
      soft palate defects were associated with cocaine abuse and extranodal nasal
      lymphoma.

PMID- 15490568
TI  - Chronic invasive fungal rhinosinusitis: two new cases and review of the
      literature.
AB  - BACKGROUND: Chronic invasive fungal rhinosinusitis is rare in the immunocompetent
      patient. Few cases have been published except for in a specific geographic area
      (Sudan, India). METHODS AND RESULTS: We reported two new cases of chronic
      invasive fungal rhinosinusitis due to Aspergillus, which was successfully
      treated, to analyze the different clinical, radiological, and mycological
      criteria. CONCLUSION: Through these two new clinical cases and the analysis of
      the literature, we suggested, in the absence of general agreement on the surgical
      and medical management, the current strategies available for this rare pathology.
      New antifungal drugs seem to be an efficient alternative to classic antifungal
      agents, especially those that require an extended course of oral therapy for the
      chronic invasive form.

PMID- 15490569
TI  - Pulmonary arterial pressure in children with allergic rhinitis.
AB  - BACKGROUND: Chronic upper airway obstruction may lead to increased pulmonary
      arterial pressure in childhood. Allergic rhinitis is one of the frequent causes
      of upper airway obstruction by nasal blockage. The aims of the study were to
      evaluate the pulmonary arterial pressures in children with allergic rhinitis and
      the effect of topical corticosteroid therapy. METHODS: Forty-nine children
      composed of 27 subjects with seasonal and 22 subjects with perennial allergic
      rhinitis were enrolled in this study. The pulmonary arterial pressures were
      measured by using Doppler echocardiography. RESULTS: The pretreatment pulmonary
      arterial systolic, mean, and diastolic pressures of study group were
      significantly higher than in healthy controls (p < 0.05). The pulmonary arterial
      systolic and mean pressures of the patient group significantly decreased at the
      end of study (p < 0.05), whereas the decrease of the diastolic pressure was not
      statistically significant (p > 0.05) after the treatment of a topical
      corticosteroid, mometasone furoate (100 microg per day), for 8 weeks. CONCLUSION:
      Our results showed that children with allergic rhinitis have higher pulmonary
      arterial pressure levels compared with healthy controls and that increased
      pulmonary arterial pressure levels due to allergic rhinitis are reversible by
      using nasal topical corticosteroids. Further studies are needed to determine the
      clinical aspect of increased pulmonary arterial pressure.

PMID- 15490570
TI  - Prognostic factors of maxillary sinus malignancies.
AB  - BACKGROUND: Analysis of a series of tumors of the maxillary sinus show
      contradictory outcome data. The purpose of this article was to study the
      prognostic factors that may have implications for patient management. METHODS: We
      present a retrospective review of 57 patients who underwent a maxillectomy over a
      20-year period. RESULTS: At the time of presentation, 86% of patients had
      advanced local disease (T3-T4). The 5-year disease-specific survival rate of this
      series was 39%. No significant differences on survival were observed according
      the histology of the tumor (p = 0.213), extension to the infratemporal fossa (p =
      0.314), and postoperative radiotherapy (p = 0.723). Factors that revealed a
      significant reduction of survival were skull base involvement (p = 0.013),
      involvement of the orbit (p = 0.043), and recurrent disease (p = 0.048).
      Multivariate analysis confirmed that the skull base and orbital involvement were
      significantly associated with disease-specific survival. CONCLUSION: Advanced T
      stage, base of skull involvement, orbital extension, and local recurrence are
      highly predictive of poor survival.

PMID- 15490571
TI  - Endoscopic resection of sinonasal malignancies: a preliminary report.
AB  - BACKGROUND: A minimally invasive endoscopic approach for the management of
      sinonasal malignancy offers several advantages including excellent illumination,
      maximal preservation of uninvolved vital structures, and sparing of facial
      incisions. The purpose of this study was to evaluate the outcome and morbidity of
      endoscopic resection with or without combined radiotherapy and/or chemotherapy.
      METHODS: Forty-seven patients with sinonasal malignancy were diagnosed and/or
      treated with an endoscopic approach at The Cleveland Clinic Foundation and The
      University of Pennsylvania Medical Center from 1996 to 2003. Nineteen patients
      fulfilled the study criteria and had a minimally invasive endoscopic resection.
      Fifteen patients were treated with curative intent and four patients underwent
      palliative resection. RESULTS: The mean age was 56.9 (9-78 years) years and the
      mean follow-up period was 26.4 months. Combined radiation with or without
      chemotherapy pre- or postoperatively was given to 15 of 19 (78.9%) patients.
      Thirteen patients were resected strictly with an endoscopic approach and six
      patients were resected in combination with neurosurgery. There were no peri- and
      postoperative deaths. The local recurrence (LR) rate was 26.3% (5/19) and the
      distant metastasis rate was 15.8% (3/19). Overall survival rate (OS) was 78.9%
      (15/19) at a mean follow-up duration of 32.1 (4-74 months) months. The disease
      free survival (DFS) rate was 68.4% (13/19) by clinical, endoscopic, and
      radiographic surveillance at a mean follow-up duration of 33.1 months. Patients
      treated with curative intent had LR, OS, and DFS rates of 21.4, 85.7, and 85.7%,
      respectively, and the patients treated for palliation had LR, OS, and DFS rates
      of 40, 60, and 15%, respectively. CONCLUSION: Minimally invasive endoscopic
      resection of sinonasal malignancy in combination with adjunctive therapies
      reduces treatment morbidity and yields LR, OS, and DFS rates that are comparable
      with traditional anterior craniofacial approaches.

PMID- 15490572
TI  - Outcomes of frontal mucocele marsupialization: endonasal and external approaches.
AB  - BACKGROUND: Frontal sinus mucoceles are known to undergo repeated recurrences,
      and the management of this disease constitutes a challenge regarding the ideal
      treatment. The aim of this study was to evaluate the postoperative results of the
      endoscopic ventilation approach in the treatment of frontal mucoceles. METHODS:
      We retrospectively reviewed the charts of 24 subjects with mucocele who underwent
      endoscopic marsupialization. The preoperative characteristics of the frontal
      sinus on computed tomography scans were compared with the postoperative results.
      RESULTS: Postoperative endoscopic examination revealed in 15 nasal sides wide
      patency of the frontal outflow tract. The ostium was patent but had become
      slightly narrowed in nine nasal sides. Restenosis of the ostium was found in six
      cases. CONCLUSION: A membranous type of obstruction in the region of the frontal
      outflow tract was related to a better outcome.

PMID- 15490573
TI  - Endoscopic sinus surgery in patients with chronic hepatic failure awaiting liver
      transplant.
AB  - BACKGROUND: Because of the need for posttransplant immunosuppression, patients
      with chronic liver failure requiring transplantation must be free of infection to
      maintain an active status on the transplant list. These patients present
      significant surgical risks due to coagulopathy. Here, we present our experience
      with endoscopic sinus surgery for medically refractory sinusitis in this patient
      population. METHODS: We created a prospective case series of seven patients
      undergoing 10 surgeries. RESULTS: All patients were given preoperative blood
      product infusions. Operative blood loss ranged from 150 to 1500 cc with an
      average of 495 cc. Two cases had to be stopped before completion because of
      bleeding obscuring visualization. The two cases with the greatest blood loss were
      in patients with the most severe liver disease (highest mathematical model for
      end-stage liver disease scores), lowest albumin, and most extensive sinus
      disease. All patients were returned to active status on the liver transplant list
      and four patients have undergone liver transplantation. CONCLUSION: Patients with
      chronic hepatic disease awaiting liver transplant can be treated successfully
      with endoscopic sinus surgery, but significant perioperative bleeding may not be
      avoidable. Preoperative use of fresh frozen plasma, platelets, and sometimes
      albumin are necessary, and postoperative blood products may be required with more
      significant sinus and liver disease. NovoSeven (recombinant factor Vlla) was used
      on two occasions in one patient, with maximal correction of the patient's
      coagulopathy. Patients should be counseled on the possible need for additional
      procedures to adequately clear disease.

PMID- 15490574
TI  - The learning curve in minimally invasive pituitary surgery.
AB  - BACKGROUND: Minimally invasive pituitary surgery (MIPS) is performed via an
      endoscopic transnasal transsphenoidal approach. This provides excellent
      illumination, visualization, and magnification of the operative field, in
      addition to avoiding complications associated with other approaches. In this
      study we examined the first 45 cases of MIPS to determine if a learning curve
      exists for this technique. METHODS: A retrospective chart review was performed of
      the first 45 cases of MIPS at a major academic medical center. Cases were divided
      into three groups of 15 patients each. Group characteristics including age, sex,
      and revision surgery were compared. Complication rates investigated included
      death, intracerebral hemorrhage, intraoperative cerebrospinal fluid leak,
      postoperative cerebrospinal fluid leak, use of lumbar drain, meningitis,
      postoperative epistaxis, ophthalmoplegia, visual impairment, and diabetes
      insipidus. Other factors examined included intraoperative blood loss, length of
      stay, and tumor histology. One way analysis of variance statistical analysis was
      used to determine the significance of differences between groups. RESULTS: Groups
      were comparable in respect to characteristics studied. Statistically significant
      (p < 0.05) differences in complication rates and other factors between groups
      were not shown. Complication rates are low. CONCLUSION: This study does not
      establish a learning curve for our first 45 cases of MIPS. This finding supports
      the concept that an otolaryngology/neurosurgery team skilled in endoscopic
      techniques and pituitary surgery can safely transition from open approaches to an
      endoscopic approach in pituitary surgery.

PMID- 15490575
TI  - [Academician Ivan Ivanovich Shmalgauzen].

PMID- 15490576
TI  - [Molecular markers and modern phylogenetics of mammals].
AB  - Application of modern molecular techniques such as molecular cloning, sequences
      and polymerase chain reaction of DNA resulted in the increasing of resolution of
      the phylogenetic analysis and enhanced the role of molecular markers in the
      evolutionary and taxonomic studies. However, certain properties of the molecular
      markers are to be taken into consideration when results of the molecular
      phylogenetic analyses are discussed. This survey reviews the advantages and
      shortages of different molecular markers (mtDNA and nDNA genes, satellite
      sequences, long and short retroposons) at the various taxonomic levels. The most
      part of new phylogenetic reconstructions are established on the results of mtDNA
      analysis and must be interpreted cautiously because of non-mendelian inheritance
      of mitochondrial genome. The extremely rapid rate of nucleotide change in mtDNA
      as compared with nDNA reinforces the saturation in nucleotide sequence and
      screens the phylogenetic signal. The analysis of nuclear genomes in constrained
      by that only truly orthologous genes are suitable for the phylogeny
      reconstruction. So there is a problem to distinguish genes from pseudogenes.
      Besides, there are some general problems of gene reconstruction such as
      nucleotide and amino acid compositional shift, long branch attraction and the
      choice of outgroup. Short interspersed nuclear elements (SINEs) may provide the
      most valuable phylogenetic information. The markers of multilocus DNA analysis
      (RAPD-PCR, IS-PCR, RELP, ISSR-PCR), their advantages and shortages are also
      discussed. A brief survey of the recent studies of molecular phylogeny of mammals
      for the period of about ten years is presented. The results based on the combined
      analysis of the mitochondrial and nuclear genes reject the reliability of some
      previously recognized supraordinal Eutherian taxa in favour of independent range
      of four main super-order clades: Afrotheria, Xenarthra, Euarchontoglires, and
      Laurasiatheria. Within these clades, monophyly of some of traditionally
      recognized orders was proved by molecular data. The recent advances of molecular
      phylogenetics are very encouraging. However, its future developments are full off
      serious difficulties. The problem of accumulation of the data turns into the
      problem of their correct analysis that is more difficult from the methodological
      point of view. The careful analysis of the conformities and contradictions
      between different data sets and looking for congruent conclusions deduced from
      different characters are the most fruitful way of further phylogenetic
      development.

PMID- 15490577
TI  - [Pseudogenes: structure conservation, expression, and functions].
AB  - Pseudogenes have been defined as nonfunctional sequences of genomic DNA (junk
      DNA) originally derived from functional genes. It is therefore assumed that
      pseudogenes are not subject to natural selection and consequently pseudogene
      mutations are selectively neutral and have equal probability to become fixed in
      the population. We describe some unexpected features of pseudogenes in diverse
      organisms that are inconsistent with this widely accepted point of view.
      Pseudogenes are often evolutionary conserved and transcriptionally active.
      Moreover, pseudogenes that have been suitably investigated often exhibit
      functional roles, such as gene regulation, generation of genetic diversity, and
      other features that are expected in genes or DNA sequences that have functional
      roles. A review of the evidence leads to the conclusion that pseudogenes are
      important components of genomes, representing a repertoire of sequences available
      for functional evolution and subject to non-neutral evolutionary changes.
      Pseudogenes might be considered as potogenes, i.e. DNA sequences with a
      potentiality for becoming new genes or acquire new functions. Furthermore we
      conjecture that some pseudogenes along with their parental sequences may
      constitute sets of indivisible functionally interacting entities (intergenic
      complexes or "intergenes"), in which all the component elements are required in
      order to fulfill a collective functional role.

PMID- 15490578
TI  - [Animal ontogenetic cell signaling pathways by the example of Notch cascade of
      Drosophila melanogaster].
AB  - Intercellular communications are coordinated in developing vertebrates and
      invertebrates embryos by a few signaling pathways. Structural and functional
      components of the pathways are encoded by cascade of genes. The signal
      transduction from cell surface to the nucleus is the common feature of these
      pathways. It is initiated by interaction of secreted ligand (signal) with the
      outer segment of transmembrane receptor. Then, activation of the intracellular
      segment of receptor provides modification of signal transducers in cytoplasm
      including transcription factors that regulates expression of target genes. Cell
      signal transduction development is conserved between species. In individual
      organism signal pathways provide various responses due to a time or spatial
      disjunction of gene expression. Morphogenetic features, genetic structure and
      signal transduction sequence of events are considered by the example of Notch
      cascade of Drosophila melanogaster.

PMID- 15490579
TI  - [Foundations of the new phylogenetics].
AB  - Evolutionary idea is the core of the modern biology. Due to this, phylogenetics
      dealing with historical reconstructions in biology takes a priority position
      among biological disciplines. The second half of the 20th century witnessed
      growth of a great interest to phylogenetic reconstructions at macrotaxonomic
      level which replaced microevolutionary studies dominating during the 30s-60s.
      This meant shift from population thinking to phylogenetic one but it was not
      revival of the classical phylogenetics; rather, a new approach emerged that was
      baptized The New Phylogenetics. It arose as a result of merging of three
      disciplines which were developing independently during 60s-70s, namely
      cladistics, numerical phyletics, and molecular phylogenetics (now basically
      genophyletics). Thus, the new phylogenetics could be defined as a branch of
      evolutionary biology aimed at elaboration of "parsimonious" cladistic hypotheses
      by means of numerical methods on the basis of mostly molecular data. Classical
      phylogenetics, as a historical predecessor of the new one, emerged on the basis
      of the naturphilosophical worldview which included a superorganismal idea of
      biota. Accordingly to that view, historical development (the phylogeny) was
      thought an analogy of individual one (the ontogeny) so its most basical features
      were progressive parallel developments of "parts" (taxa), supplemented with
      Darwinian concept of monophyly. Two predominating traditions were diverged within
      classical phylogenetics according to a particular interpretation of relation
      between these concepts. One of them (Cope, Severtzow) belittled monophyly and
      paid most attention to progressive parallel developments of morphological traits.
      Such an attitude turned this kind of phylogenetics to be rather the semogenetics
      dealing primarily with evolution of structures and not of taxa. Another tradition
      (Haeckel) considered both monophyletic and parallel origins of taxa jointly: in
      the middle of 20th century it was split into phylistics (Rasnitsyn's term; close
      to Simpsonian evolutionary taxonomy) belonging rather to the classical realm, and
      Hennigian cladistics that pays attention to origin of monophyletic taxa
      exclusively. In early of the 20th century, microevolutionary doctrine became
      predominating in evolutionary studies. Its core is the population thinking
      accompanied by the phenetic one based on equation of kinship to overall
      similarity. They were connected to positivist philosophy and hence were
      characterized by reductionism at both ontological and epistemological levels. It
      led to fall of classical phylogenetics but created the prerequisites for the new
      phylogenetics which also appeared to be full of reductionism. The new rise of
      phylogenetic (rather than tree) thinking during the last third of the 20th
      century was caused by lost of explanatory power of population one and by
      development of the new worldview and new epistemological premises. That new
      worldview is based on the synergetic (Prigoginian) model of development of non
      equilibrium systems: evolution of the biota, a part of which is phylogeny, is
      considered as such a development. At epistemological level, the principal premise
      appeared to be fall of positivism which was replaced by post-positivism
      argumentation schemes. Input of cladistics into new phylogenetics is twofold. On
      the one hand, it reduced phylogeny to cladistic history lacking any adaptivist
      interpretation and presuming minimal evolution model. From this it followed
      reduction of kinship relation to sister-group relation lacking any reference to
      real time scale and to ancestor-descendant relation. On the other hand,
      cladistics elaborated methodology of phylogenetic reconstructions based on the
      synapomorphy principle, the outgroup concept became its part. The both inputs
      served as premises of incorporation of both numerical techniques and molecular
      data into phylogenetic reconstruction. Numerical phyletics provided the new
      phylogenetics with easily manipulated algorithms of cladogram construing and thus
      made phylogenetic reconstructions operational and repetitive. The above phenetic
      formula "kinship = similarity" appeared to be a keystone for development of the
      genophyletics. Within numerical phyletics, a lot of computer programs were
      elaborated which allow to manipulate with evolutionary scenario during
      phylogenetic reconstructions. They make it possible to reconstruct both clado-
      and semogeneses based on the same formalized methods. Multiplicity of numerical
      approaches indicates that, just as in the case of numerical phenetics, choice of
      adequate method(s) should be based on biologically sound theory. The main input
      of genophyletics (= molecular phylogenetics) into the new phylogenetics was due
      to completely new factology which makes it possible to compare directly such far
      distant taxa as prokaryotes and higher eukaryotes. Genophyletics is based on the
      theory of neutral evolution borrowed from microevolutionary theory and on the
      molecular clock hypothesis which is now considered largely inadequate. The future
      developments of genophyletics will be aimed at clarification of such fundamental
      (and "classical" by origin) problems as application of character and homology
      concepts to molecular structures. The new phylogenetics itself is differentiated
      into several schools caused basically by diversity of various approaches existing
      within each of its "roots". Cladistics makes new phylogenetics splitted into
      evolutionary and parsimonious ontological viewpoints. Numerical phyletics divides
      it into statistical and (again) parsimonious methodologies. Molecular
      phylogenetics is opposite by its factological basis to morphological one. The new
      phylogenetics has significance impact onto the "newest" systematics. From one
      side, it gives ontological status back to macrotaxa they have lost due to "new"
      systematics based on population thinking. From another side, it rejects some
      basical principles of classical phylogenetic (originally Linnean) taxonomy such
      as recognitions of fixed taxonomic ranks designated by respective terms and
      definition of taxic names not by the diagnostic characters but by reference to
      the ancestor. The latter makes the PhyloCode overburdened ideologically and the
      "newest" systematics self-controversial, as concept of ancestor has been
      acknowledged non-operational from the very beginning of cladistics. Relation
      between classical and new phylogenetics is twofold. At the one hand, general
      phylogenetic hypothesis (in its classical sense) can be treated as a combination
      of cladogenetic and semogenetic reconstructions. Such a consideration is bound to
      pay close attention to the uncertainty relation principle which, in case of the
      phylogenetics, means that the general phylogenetic hypothesis cannot be more
      certain than any of initial cladogenetic or semogenetic hypotheses. From this
      standpoint, the new phylogenetics makes it possible to reconstruct phylogeny
      following epistemological principle "from simple to complex". It elaborates a
      kind of null hypotheses about evolutionary history which are more easy to test as
      compared to classical hypotheses. Afterward, such hypotheses are possible to be
      completed toward the classical, more content-wise ones by adding anagenetic
      information to the cladogenetic one. At another hand, reconstructions elaborated
      within the new phylogenetics could be considered as specific null hypotheses
      about both clado- and semogeneses. They are to be tested subsequently by mean of
      various models, including those borrowed from "classical" morphology. The future
      development of the new phylogenetics is supposed to be connected with getting out
      of plethora of reductionism inherited by it from population thinking and
      specification of object domain of the phylogenetics. As the latter is a part of
      an evolutionary theory, its future developments will be adjusted with the latter.
      Lately predominating neodarwinism is now being replaced by the epigenetic
      evolutionary theory to which phylistics (one of the modern versions of classical
      phylogenetics) seems to be more correspondent.

PMID- 15490580
TI  - [The 100-years anniversary of Ernst Mayr].

PMID- 15490581
TI  - MNA executive director Betty Dickson retires after 16 years with MNA.

PMID- 15490582
TI  - Holes in the health insurance system--who lacks coverage and why.

PMID- 15490583
TI  - The consequences of uninsurance for individuals, families, communities, and the
      nation.

PMID- 15490584
TI  - The current state of employment-based health coverage.

PMID- 15490585
TI  - The struggle for the soul of Medicare.

PMID- 15490586
TI  - Attending to Medicaid.

PMID- 15490587
TI  - Health reform and the safety net: big opportunities; major risks.

PMID- 15490588
TI  - Why can't we do what they do? National health reform abroad.

PMID- 15490589
TI  - Where do we go from here: is there any hope for real health care reform?

PMID- 15490590
TI  - Numbers matter: a guide to cost and coverage estimates in health reform debates.

PMID- 15490591
TI  - In the shadow of 9/11: health care reform in the 2004 presidential election.

PMID- 15490592
TI  - Crowd-out and the politics of health reform.

PMID- 15490593
TI  - Conflict and compromise over tradeoffs in universal health insurance plans.

PMID- 15490594
TI  - Litigation in clinical research: malpractice doctrines versus research realities.

PMID- 15490595
TI  - "Underground euthanasia" and the harm minimization debate.

PMID- 15490596
TI  - Conserving scarce resources: willingness of health insurance enrollees to choose
      cheaper options.

PMID- 15490597
TI  - Governing the globalization of public health.

PMID- 15490598
TI  - Health of the people: the highest law?

PMID- 15490599
TI  - Tobacco control legislation: tools for public health improvement.

PMID- 15490600
TI  - The United State Supreme Court and health law: the year in review. The Supreme
      Court federalizes managed care liability.

PMID- 15490601
TI  - Recent developments in health law. UCLA Willed Body Program comes under scrutiny
      as companies sued for the purchase of body parts.

PMID- 15490602
TI  - Currents in contemporary ethics. Discerning minimal risk in research involving
      prisoners as human subjects.

PMID- 15490603
TI  - Hedging their bets. Strong market performance is delivering pleasantly surprising
      results for investments made by not-for-profits.
AB  - CFOs aren't partying like it's the 1990s, but healthcare portfolios did deliver
      double-digit increases in 2003, a Commonfund Institute survey said. Executives,
      seeking to avoid losses, have invested in controversial hedge funds, which have
      become a little too popular, says the institute's executive director, John
      Griswold, left.

PMID- 15490604
TI  - No more Mr. Nice Guys. Proposed restrictions force GPOs to pull out big guns.

PMID- 15490605
TI  - Poor performance. AHA suffers year-end loss for second year in a row.

PMID- 15490606
TI  - California healing. State survey shows waning patient satisfaction.

PMID- 15490607
TI  - In Ivan's wake. All four Pensacola hospitals rely on generators.

PMID- 15490608
TI  - Making its mark. PacifiCare buys American Medical, expands market.

PMID- 15490609
TI  - Switch, don't fight. GPOs would do well to work with federal officials before the
      hammer falls.

PMID- 15490610
TI  - Priority dichotomy. Healthcare is central to Kerry's campaign, while Bush keeps
      focus on security.

PMID- 15490611
TI  - 2004 Up & Comers. Meet this year's class of rising young stars in healthcare
      management.

PMID- 15490612
TI  - By the numbers. Top retained executive search consulting firms.

PMID- 15490613
TI  - [The MMP makes a study...].

PMID- 15490614
TI  - [Cetuximab. A monoclonal antibody against the EGF receptor].

PMID- 15490615
TI  - [Urticaria-eczema-psoriasis. Diagnosis, etiology and therapy].

PMID- 15490616
TI  - [What is a cost-effectiveness analysis?].

PMID- 15490617
TI  - [Nausea and vomiting in pregnancy].

PMID- 15490618
TI  - [Cold preparations in pregnancy?].

PMID- 15490619
TI  - [Nasal spray for earache?].

PMID- 15490620
TI  - [New approaches to prophylaxis of oncologic morbidity associated with
      environmental chemical hazards].
AB  - The author suggested a new algorithm of State Sanitary Epidemiologic Supervision
      activities on oncologic morbidity prophylaxis. The algorithm takes into account
      environmental content not only of chemical carcinogens, but also of so-called
      modifiers--nonspecific chemical pollutants that lower threshold of human
      sensitivity to carcinogenic effects and intensify carcinogenesis.

PMID- 15490621
TI  - [Features of heart function and morphology in chronic organic solvents
      intoxication].
AB  - Patients with chronic organic solvents intoxication are characterized by left
      ventricle hyperfunction mostly isometric type, with left ventricle diastole
      disordered due to impaired both passive filling and active relaxation, given the
      chamber geometry is normal and hypokinetictype hemodynamics is prevalent. Phase
      analysis of left heart mechanic activity in patients with chronic organic
      solvents intoxication demonstrated I degree hypodinamia syndrome and left
      ventricle outlet stenosis.

PMID- 15490622
TI  - [Role of environmental pollution with heavy metals in chronic pulmonary diseases
      pathogenesis in North regions].
AB  - Accumulation of Cu, Zn, Mn, Ni, Pb, Cd in biologic materials causes microelements
      imbalance and metabolic disorders affecting also redox reactions, immune system
      and respiratory organs and functions, therefore leading to chronic pulmonary
      diseases. The authors suggested a hypothesis on links between environmental
      pollution, disorders of microelements metabolism and chronic pulmonary diseases
      pathogenesis in North region dwellers.

PMID- 15490623
TI  - [Biologic markers and occupational monitoring of human exposure to exhaust gases
      of diesel engines].
AB  - The article presents results of studies covering changes in porphyrin and heme
      synthesis in lymphocytes of miners exposed to exhaust gases of diesel engines.

PMID- 15490624
TI  - [Relationships between centers in brain cortex under chronic exposure to
      occupational hazards].
AB  - The authors conclude that breakdown of long-term cerebral adaptation to prolonged
      occupational hazards manifests itself as various types of disordered
      relationships between brain hemispheres. Evidence is that value and direction of
      changes in coherence (interrelationship) of EEG rhythms between symmetrical zones
      of brain cortex, spatial distribution of these changes, although lacking strict
      specificity, reflect stress phenomena in higher divisions of CNS and are
      interesting for solving problems of occupational conditionality of general
      unfavorable reactions in the system.

PMID- 15490625
TI  - [Prevalence of skin diseases in certain occupational groups on motor transport
      enterprises].
AB  - The article covers results of studies concerning prevalence of skin diseases
      among drivers, repair and service workers, managers of motor transport
      enterprises.

PMID- 15490626
TI  - [Some features of cardiovascular diseases caused by exposure to lead and copper
      compounds].
AB  - Lead and copper induce a certain reaction of cardiovascular system, different
      from reactions to individual metals, as shown in metallurgic alloys production
      workers. The reaction is not equal to the reactions sum and could be considered
      as a subadditive property or as a variant of toxicologic antagonism. Experimental
      studies of animals exposed to technologic compositions of lead and copper support
      the thesis including also lead gonadotoxicity.

PMID- 15490627
TI  - [Evaluating individual carcinogenic risk in contact with lubricating-freezing
      technologic substances].

PMID- 15490628
TI  - [Contemporary medical and biologic problems of organization and performance of
      fire fighting service].

PMID- 15490629
TI  - [Hepatobiliary system in workers exposed to hepatotropic chemicals].

PMID- 15490630
TI  - [Renal function in rats facing water and salt load under exposure to cadmium
      dichloride].

PMID- 15490631
TI  - [Surgical treatment for asymptomatic non-ruptured intracranial aneurysms].
AB  - The study was undertaken to analyze the outcomes of treatment in 37 patients with
      44 non-ruptured aneurysms (NRA) at different sites. The paper presents a detailed
      classification of NRA, identifies individuals at risk for aneurysmal disease in
      whom an active search for aneurysms until they rupture is recommended to prevent
      aneurysmal subarachnoidal hemorrhages and their sequels. Total aneurysmal
      exclusion was achieved in 93.2% of the cases; the aneurysmal walls were
      consolidated with surgical gauze in 7.2%. There were no fatal cases.
      Postoperative progression of focal neurological symptoms was noted in 4 patients.
      In 3 patients, these symptoms were entirely reversible. All NRAs should be
      operated on irrespective of their size particularly in young and middle-aged
      patients since this is technically possible and there are no concomitant diseases
      that make surgery contraindicated. It is expedient to perform computed or
      magnetic resonance imaging in combination with angiography in risk-group patients
      in order to reveal or exclude aneurysm.

PMID- 15490632
TI  - [A follow-up of patients operated on for acute arterial aneurysmal rupture].
AB  - The paper analyzes the long-term results of treatment and assesses the quality of
      life in patients admitted to the N. N. Burdenko Research Institute of
      Neurosurgery, Academy of Medical Sciences, for acute subarachnoidal hemorrhage
      (ASH) from arterial aneurysms. The study was based on the questioning survey of
      168 patients and/or their relatives in the periods of 1 to 7 years after ASH and
      surgery. The findings have indicated that the pattern of outcomes in the late
      periods after ASH and surgery differs from that in the early periods after the
      onset of the disease. These differences concern all types of outcome. Recovery of
      cerebral functions continues for a long period of time. As the rehabilitative
      period passes, neurological disorders are absent or mild in 55% of the patients.
      The patients with significant neurological defects reduced in number by three
      times as compared with that on discharge and accounted for 9.7%. At the same time
      the death caused by the underlying disease occurred in the late postoperative
      periods in 7 cases. In this connection, the outcomes of the disease should be
      finally assessed in the periods of not earlier than half a year after surgery.
      80.7% of the patients operated on are completely adapted in everyday life; 9%
      need an occasional aid; 7.1% entirely depend on other people; 42% of the patients
      work; however, only 27.1% of the patients returned to their former work and 23.2%
      cannot work due to their prior disease. The highest disability rates and hence a
      low life quality are observed in patients operated on at Hunt-Hess stages IV-V.
      The findings suggest that the brain is highly plastic and that efforts and
      material costs on the nursing and rehabilitation of patients with ASH yield good
      results.

PMID- 15490633
TI  - [Comparative assessment of the results of different surgical treatments in
      patients with pituitary adenomas infiltrating the cavernous sinus].
AB  - Benign pituitary tumors or adenomas are highly common, occasionally inclined to
      infiltrate the adjacent structures, the cavernous sinus in particular. Despite
      the fact that drug and radiation therapy are at present widely used treatments,
      surgical procedures remain highly topical. Different modifications of two basic
      surgical methods (transcranial intradural and transsphenoidal) that fail to
      completely remove a tumor from the cavernous sinus in most cases are mostly
      frequently used as before. Attempts to improve surgical procedures and
      introduction of current technologies have led to the emergence of an extradural
      method for tumor removal from the cavernous sinus and to the introduction of
      endoscopic monitoring during transsphenoidal operations. A strategy of two-stage
      removal of pituitary tumors has simultaneously been developed. The paper presents
      the results of surgical treatment of 297 patients with pituitary adenomas growing
      into the cavernous sinus, by using currently available procedures:
      transsphenoidal, transcranial intradural, and intra-extradural, and two-stage
      ones. The findings have confirmed that transsphenoidal removal of pituitary
      adenomas is the safest method. However, this method has a number of limitations
      in cases with tumor being grown into the cavernous sinus especially when there is
      a medial displacement of the intracavernous segment of the internal carotid
      artery. Moreover, secondary tumor nodes that may be removed by transcranial
      intradural access are a contraindication to its use. With this, attempts to
      remove a tumor from the cavernous sinus fail to ensure the desired completeness
      of removal from the cavernous sinus. The application of an intra-extradural
      access is the most adequate procedure for tumor removal from the cavernous sinus.
      The two-stage removal is the most adequate procedure in cases of simultaneously
      significant spread of a tumor intracranially and into the structures of the base
      of the skull.

PMID- 15490634
TI  - [Basilar skull fractures: clinical and prognostic aspects].
AB  - The incidence of basilar skull fractures and their clinical and prognostic
      aspects were studied in victims with varying severity of brain injury. Of 947
      cases, 449 (46%) patients were diagnosed as having basilar skull fracture and 181
      (18.6%) had basal spinal fluid leakage. The frequency of fractures and basal
      spinal fluid leakage increased in proportion to the severity of brain injury. The
      above 14-day history of spinal fluid leakage was an absolute indication for
      surgical fistula closure.

PMID- 15490635
TI  - [Meningiomas of the wings of the basilar bone in patients undergone a course of
      radiation therapy for retinoblastoma in infancy (analysis of 3 cases)].
AB  - The paper presents 3 cases of radio-induced meningiomas in patients who underwent
      irradiation for retinoblastoma in infancy. Meningiomas of the middle cranial
      fossa were diagnosed in women aged 16, 34, and 47 years. Radiation therapy was in
      the complex treatment of retinoblastoma in all patients in infancy (4 months to 3
      years). The latent period between the irradiation and diagnosis of meningioma was
      15 to 44 years. The location of detected meningiomas (the wings of the basilar
      bone on the side of exenteration or enucleation) corresponded to the irradiation
      fields. Surgical treatment yielded good results. Histological study has indicated
      that meningiomas were fibroblastic in the former two cases and atypical
      meningioma was verified in the third case when the tumor infitratively spread.
      Our observations support the fact that there may be radio-induced meningiomas in
      the area exposed to irradiation.

PMID- 15490636
TI  - [Combined surgical treatment for carotid paraganglioma].
AB  - The paper gives a clinical example of embolization of the vascular network of
      carotid paraganglioma with subsequent en-block tumor removal with bifurcation of
      the common carotid artery and with recovery of great blood flow along the
      internal carotid artery through alloprosthesis of the latter. The positive
      effects of a combination of endovascular embolization of the vascular network of
      the tumor with its subsequent removal are noted. Indications for endovascular
      embolization and its procedure, intraoperative evaluation of cerebral collateral
      circulation are discussed. Those for carotid repair during en-block removal of
      carotid paraganglioma with bifurcation of the common carotid artery are
      considered.

PMID- 15490637
TI  - [Aspergillosis of the central nervous system (clinical observation and review of
      literature)].
AB  - Aspergillosis of the central nervous system presents a challenge faced with the
      problems arising from the establishing the diagnosis, the low efficiency of
      treatment, and high mortality rates (about 95% as shown by some data). This paper
      presents a clinical case of a patient with aspergillosis-induced central nervous
      system lesion verified by autopsy. Possible errors in the diagnosis and treatment
      of the patient are analyzed. The literature data including clinical cases,
      etiopathogenesis, and clinical manifestations and its possible complications are
      presented. Groups of patients at risk for invasive aspergillosis are considered.
      The paper gives the data available in the foreign literature on the methods and
      efficiency of treatment and mortality rates in different groups of patients. The
      urgency of the problem in the diagnosis and treatment of cerebral aspergillosis
      rises with the increased number of patients with immunological disorders due to
      infectious diseases (HIV), social (drug addiction, alcoholism), environmental,
      and other factors.

PMID- 15490638
TI  - [Water-electrolyte and endocrine disorders after craniopharyngomectomy in a
      child].
AB  - The paper considers a type of three-phase course of diabetes insipidus with the
      development of the syndrome of inadequate secretion of antidiuretic hormone
      (SIADH) in a child after radical removal of endosupracellar craniopharyngoma. The
      parameters of cerebral blood flow, homeostatic fluctuations, the blood levels of
      thyroid hormones were compared with the time course of changes in the patient's
      clinical status. SIADH was accompanied by impaired consciousness, convulsion,
      developed common edematous syndrome, including interstitial edema of the lung,
      progressive suprarenal and thyroid insufficiency. The concurrence of SIADH with
      polyhormonal deficiency and the edematous syndrome determined the lines of
      intensive care.

PMID- 15490639
TI  - [The specific features of infusion therapy in patients with acute aneurysmal
      subarachnoidal hemorrhage].

PMID- 15490640
TI  - [Improvement of care to victims with combined skull-brain injury].

PMID- 15490641
TI  - Generational issues in nursing.

PMID- 15490642
TI  - Preventing back injuries: safe patient handling and movement.

PMID- 15490644
TI  - Insurance coverage for nurses.

PMID- 15490645
TI  - A nurse's story of hurricane Charley.

PMID- 15490646
TI  - Clinical excellence exemplar: "What if it was me"?

PMID- 15490649
TI  - Nursing value: connectedness.

PMID- 15490650
TI  - [The dynamic rate of morbidity among the residents in a number of Russia's
      northern regions].
AB  - Discussed in the paper are the peculiarities related with the morbidity observed
      in a number of Russia's northern regions; a conclusion is made on that it is
      necessary to take account of the above specific features while rendering the
      medical care.

PMID- 15490651
TI  - [A comparative evaluation of the health of children based on the results of
      medical check-ups and questionnaires].
AB  - Objective evaluations of population's health belong to the most important tasks
      of the public-health science. Such evaluations made in respect to children are of
      extra importance. One must comprehensively understand the potentialities and
      abilities of the methods used for the purpose. A comparative evaluation of 387
      children, aged 10, was based on the findings of medical check-ups and on
      questionnaires of their parents. 37.7% of children, who were evaluated by their
      mothers as having good health, were diagnosed by doctors as having a chronic
      disease, i.e. the diagnosis did not entail any life limitations for such
      children. 40% of those children, who were referred to by their parents as sick
      (poor health), were classified by doctors as belonging not to category 3 (chronic
      pathology) but to a category of healthier children (category 2). Below 10% of
      children, who were describe by their parents as having poor health, were among
      those who were put by doctors on the list of group 3 on the basis of medical
      check-ups. As for those children who had an actively displayed chronic disease
      with a pronounced clinical course, like bronchial asthma, ulcer etc., the
      opinions of doctors and of their parents coincided in a majority of cases. The
      comparative evaluations of children' health based on questionnaires of their
      parents and on medical check-ups exposed a certain coincidence and specificity of
      such evaluations since they are based on different approaches.

PMID- 15490652
TI  - [An analysis of the medico-social situation in regions (on the basic of
      sociological research)].

PMID- 15490653
TI  - [A complex evaluation of the physical health of children, teenagers and youth in
      Eastern Siberia].

PMID- 15490654
TI  - [Occupational morbidity of coal miners].
AB  - The legal basis and occupational morbidity of coal miners are discussed for
      different Russia's regions under the conditions of the market reform. The legal
      basis was shown as not ensuring the regulated mutual assistance between employee
      and employer in cases, when the initial signs of an occupational disease are
      detected.

PMID- 15490655
TI  - [Topical issues related with promoting the healthcare in subjects of the Russian
      Federation].

PMID- 15490656
TI  - [The progress of psychotherapy in Russia].

PMID- 15490657
TI  - [Regular medical check-ups of industrial workers in the city of Kazan].
AB  - The organization of preliminary medical check-ups (PMC) and regular medical check
      ups (RMC) of industrial workers is discussed under the conditions of the reform
      of the medical preventive care in the city of Kazan (at the stabilization stage).
      Data are presented on advancing and enhancing the efficiency of PMC and RMC in
      the major industrial city of the Tatar Republic.

PMID- 15490658
TI  - [The specificity of organization of the consultative-and-diagnostic service for
      the adult population in a big city].
AB  - The volume and structure of the diagnostic services and of the medical aid
      appealability were analyzed for the Eastern Administrative District of Moscow by
      the example of a stage-2 diagnostic-and-consultative center. The analysis was
      made on the basis of 80233 receipts of patients for the period of January-April
      2003. Three types of patients' flow were defined with respect to the purpose of
      visit: consultative aid (CA, 17.3%), consultative-and-diagnostic aid (CDA, 16.2%)
      and diagnostics (D, 66.5%). Differences are shown in the structure of
      appealability by the classes of diseases (nosological forms of diseases) and
      according to groups of patients. Consultations are mostly provided in cases of
      diseases of the endocrine system (20.9%), digestive system (20.2%) blood
      circulation system (18.0%) and urogenital system (14.6%). Patients with
      urogenital disease (31.1%) and with blood-circulation lesions (13.5%) were found
      to be predominant in the CDA group. The structure of appealability is defined for
      the classes of diseases, their nosological forms and for medical specialties. It
      is pointed out that 52.1% of patients visited their general practitioners.
      Patients visited most often the doctors of the below specialties: oncology-
      16.1%, endocrinology and cardiology 12.3%, general practitioner--11.5% and
      gastroenterology--78%. The rate of visits was evaluated for the classes of
      diseases and medical fields; the estimated distribution of appealability was
      estimated with respect to the rate of visits. The structure of diagnostic
      examinations was analyzed by types, purpose, and classes of diseases (nosological
      forms).

PMID- 15490660
TI  - [Positioning of medical-sanitary units in the medical-care market].

PMID- 15490659
TI  - [Regulation of medical activity and personnel policy at a prevention and patient
      care facility].

PMID- 15490661
TI  - [Health of retired and homeless persons in Ukhta].

PMID- 15490662
TI  - [The logistics of population health protection].
AB  - The health protection of population is a subsystem of a macrosystem, i.e. of
      social sphere. The social sphere, in its turn, is a logistic macrosystem,
      therefore, the logistical principles can be applied to its subsystems. The system
      of population health protection is regarded from such standpoint in the paper;
      the dynamics of human resources are described in detail including an independent
      author's classification of it. A scheme is presented of how to manage the human
      resources evolution; effects exerted by the subsystem through the infrastructure
      on human resources are elucidated.

PMID- 15490663
TI  - [The dynamic morbidity with ischemic heart disease in the Republic of
      Kazakhstan].
AB  - A study of statistic data on the prevalence of ischemic heart disease (IHD) in
      1998-2002 in the Republic of Kazakhstan showed an uptrend. Therefore, there is a
      need in defining actual prevention measures to cut the number of primary IHD
      cases.

PMID- 15490664
TI  - [Prognostication and prevention of diseases of the nervous system in perinatal
      children].

PMID- 15490665
TI  - [Organizational aspects in the activity of diocesan orthodox hospital].

PMID- 15490666
TI  - [The 10th anniversary of obligatory medical medical insurance in Russia].

PMID- 15490667
TI  - [Moscow clinical schools of Zakhariyn and Ostroumov: succession, cooperation or
      competition?].

PMID- 15490668
TI  - [The activity of "The society of competition of the medical and physical
      sciences" during the first 20 years of its existence].

PMID- 15490669
TI  - [A rare breastplate of the first five-year plans].

PMID- 15490670
TI  - Where does health care compliance stand one year after HIPAA?

PMID- 15490671
TI  - Is security compliance just IT's problem?

PMID- 15490672
TI  - Accounting for disclosures of PHI: will we see changes?

PMID- 15490673
TI  - Pfizer: DM did not fizzle in Florida Medicaid ruckus.

PMID- 15490674
TI  - Cost-related underuse of heart meds leads to cardiac complications.

PMID- 15490675
TI  - Four physician specialties report double-digit gains.

PMID- 15490676
TI  - Managed care at the crossroads.

PMID- 15490677
TI  - O'Kane gives the ok to focus more on providers.

PMID- 15490678
TI  - CAM offerings really can enhance quality of care for some patients.

PMID- 15490679
TI  - Can physician and health plan get together over guidelines?

PMID- 15490680
TI  - Improving physician attendance at educational seminars sponsored by Managed Care
      Organizations.
AB  - PURPOSE: To enhance primary care provider participation in a multi-faceted
      interactive asthma teaching program sponsored by managed care organizations.
      DESIGN: Case series of six MCO-sponsored continuing medical education (CME)
      sessions. METHODOLOGY: MCOs were provided with a standard set of recruitment
      materials. The MCO disease management divisions invited pediatric primary care
      providers of several types to attend the asthma teaching sessions and tracked the
      type of contacts employed and the success rate. Participants were awarded CME and
      were provided with a meal to encourage attendance. The faculty included a local
      physician-leader and a regional asthma expert. The sessions were scheduled by the
      MCO, but were given by the study group using a previously developed curriculum
      that emphasized material endorsed by the National Heart Lung and Blood Institute.
      Direct costs were tracked. PRINCIPAL FINDINGS: Overall, 53 of 299 (18 percent)
      providers participated in the two-part asthma CME sessions. Recruitment was
      significantly more successful when a physician leader participated in
      solicitation of providers (P < .01). Successful recruitment generally
      necessitated two points of contact, and phone contact appeared to yield greater
      success than e-mail. Scheduling conflicts and inconvenient location were the most
      common reasons given for not attending the seminars. Ninety percent of providers
      who attended the first session completed the program. The average direct cost per
      provider was dollar 370. CONCLUSION: Even when offering primary care providers a
      multifaceted interactive asthma-teaching program, physician recruitment
      necessitates personal and multiple contacts, and careful planning in terms of
      seminar location, time, and content. Interactive physician education seminars
      necessitate a large investment of resources but may be cost-effective if care is
      improved.

PMID- 15490681
TI  - Employers take stock of illness on the clock.

PMID- 15490682
TI  - Orphan Drug Act treatments deserve full insurance coverage.

PMID- 15490683
TI  - Employers offer 'consumer' plans with trepidation.

PMID- 15490684
TI  - [Digital echocardiography laboratory].
AB  - The implementation of a digital echocardiography laboratory exists today using
      the DICOM (Digital Imaging Communication in Medicine) standard to acquire, store
      and transfer echocardiographic digital images. The components of a laboratory
      include: 1) digital echocardiography machines with DICOM output, 2) a switched
      high-speed local area network, 3) a DICOM server with abundant local storage, and
      4) a software to manage image and measurement information. The aim of this
      article was to describe the critical components of a digital echocardiography
      laboratory, discuss strategies for implementation, and describe some of the
      pitfalls that we encountered in our own implementation of the digital third level
      echocardiography laboratory.

PMID- 15490685
TI  - [Evaluation of BLS-D training in lay people].
AB  - BACKGROUND: The possibility of saving persons with sudden cardiac arrest (SCA)
      lowers of 10% every minute since the beginning of the event. The early
      defibrillation (within 4 min) of a person with SCA performed by first responders
      suitably trained increases the survival rate up to 50%. The basic aim is that
      early defibrillation is performed as soon as possible by the first responder.
      METHODS: Within the Public Access Defibrillation (PAD) "Napoli Cuore" Project,
      220 highway patrol agents of the Campania Region district were trained through
      theoretical and practical courses to acquire suitable psychomotor skills to
      perform the first aid. The learning evaluation was performed with a written exam
      and a practical test to assess how much every agent had learned about basic life
      support-defibrillation (BLS-D) schemes. RESULTS: 98.5% of the participants passed
      the exams and obtained the BLS-D rescuer license, and 15.5% of them obtained the
      highest score. The analysis of the report cards showed that most of the
      participants expressed an excellent opinion about this experience. CONCLUSIONS:
      To implement a PAD project it is necessary to awaken all the structures involved
      in the campaign against SCA. Hence, it is important that all emergency
      specialists, public institutions and police departments work all together to make
      everyone feels safe.

PMID- 15490686
TI  - [Cardiac events after carotid endarterectomy: long-term results].
AB  - BACKGROUND: The aim of this study was to evaluate the incidence of late cardiac
      events in patients submitted to carotid endarterectomy (CEA), asymptomatic for
      coronary artery disease during the carotid surgical procedure. METHODS: During a
      period of 11 years, 162 patients (122 males, 40 females, mean age 68 +/- 12
      years), asymptomatic for coronary artery disease and/or without sings of coronary
      artery disease at the cardiological screening, were submitted to CEA for
      symptomatic or severe (> or = 70%) carotid stenoses. Clinical follow-up was
      performed on 151 patients (93%), to identify the incidence of cardiac and
      neurological events and freedom from late death. The results of this group of
      patients (group A) were compared to those obtained during follow-up of 147
      patients (133 males, 14 females, mean age 69 +/- 15 years) (group B) affected by
      coronary artery disease and submitted to combined CEA and coronary artery bypass
      grafting (CABG). RESULTS: During follow-up, in group A freedom from late death,
      cardiac death and adverse neurological events were 77 +/- 4.8, 86 +/- 4.4 and
      87.3 +/- 4.5% at 9 years, respectively. Freedom from adverse neurological events
      in group A was similar to that registered in group B (86.4 +/- 5.6%, p = NS). The
      incidence of cumulative cardiac events and fatal cardiac events (myocardial
      infarction, sudden death, congestive heart failure) on the contrary, was higher
      in group A than in group B (13.2 vs 6.8%, p = 0.0424, and 7.9 vs 3.4%, p =
      0.0446, respectively). CONCLUSIONS: In patients submitted to isolated CEA,
      although without symptoms or signs of coronary artery disease at the timing of
      the carotid procedure, the possibility of a severe coronary disease development
      during follow-up is not negligible: the incidence of late cardiac events may be
      higher than in patients with coronary artery disease corrected at the same time
      of the CEA procedure. These data suggest the opportunity of a systematic
      cardiological screening during follow-up in patients submitted to isolated CEA,
      although clinically asymptomatic for coronary artery disease at the timing of the
      vascular procedure, to improve the long-term survival.

PMID- 15490687
TI  - [Echocardiographic features in a case of tuberculous lymphadenitis].
AB  - Tuberculosis can secondarily affect the heart, mainly the pericardium and less
      frequently the endocardium and coronary vessels. Tuberculous myocarditis usually
      is a post-mortem diagnosis, and affects the right atrium and left ventricle
      presenting as miliary granulomas with or without caseating necrosis, or as
      diffuse cellular infiltration. We report the case of a 65-year-old man, affected
      by tuberculous lymphadenitis, with a history of hyperkinetic atrial and
      ventricular arrhythmias. Magnetic resonance, transthoracic and transesophageal
      echocardiography showed a peculiar cardiac involvement, characterized by right
      ventricular and left atrial infiltration. As the patient refused myocardial
      biopsy, the diagnosis of tuberculous myocarditis was stated ex-adjuvantibus,
      after specific multidrug chemotherapy with complete remission of all
      echocardiographic abnormalities. Echocardiography represents a useful diagnostic
      tool in patients presenting with clinical and electrocardiographic features, that
      even not specific could be suggestive of tuberculous myocarditis, whose incidence
      could be greater than reported in the literature.

PMID- 15490688
TI  - [Two cardiac tumors with left ventricular location: myxoma and papillary
      fibroelastoma].
AB  - We report 2 clinical cases of cardiac tumors, myxoma and papillary fibroelastoma,
      with unusual ventricular location. The clinical manifestations of these entities
      are not well described. Usually the patients are asymptomatic even if they have a
      high risk for cardiac and systemic embolic events so that these neoplasms are
      recognized during life more often in patients evaluated for embolic events of
      unclear pathology. The routine use of echocardiography has increased the
      detection of these tumors in living patients. In the surgical treatment, the
      approach should allow minimal manipulation of the tumors, inspection of all four
      cardiac chambers to overlook if tumors are multifocal and provide adequate
      exposure for complete resection. In our experience, we used two surgical
      approaches, via the left ventricle and via the aortic valve.

PMID- 15490689
TI  - [Guidelines on prevention, diagnosis and treatment of infective endocarditis].

PMID- 15490690
TI  - Listening to children.

PMID- 15490691
TI  - Blueprint for children.

PMID- 15490692
TI  - Still happy after all of these years.

PMID- 15490693
TI  - Brave new world.

PMID- 15490694
TI  - Look and learn.

PMID- 15490695
TI  - Careless whispers.

PMID- 15490696
TI  - Magic touch.

PMID- 15490697
TI  - Issues affecting the growth of independent prescribing.
AB  - AIM: To investigate factors that have influenced A&E departments, minor injury
      units (MIUs) and walk-in centres (WICs) on whether or not to send nurse
      practitioners on extended nurse prescribing courses. Also, to examine the extent
      to which nurses who have completed an extended course are independently
      prescribing in their everyday practice. METHOD: A pilot study was undertaken in
      20 randomly selected units, and following minor changes the main study was
      carried out by sending a questionnaire with a stamped addressed envelope to all
      nurse managers in 307 units. The response rate was 62 per cent (n=192). RESULTS:
      The study found that 71 per cent (n=20) of WICs, 30 per cent (n=33) of A&E
      departments and 20 per cent (n=11) of MIUs have sent nurses on extended nurse
      prescribing courses. The most striking result was that 44 per cent (n=28) of
      nurses were still not prescribing even after completing the course. Patient Group
      Directions (PGDs) are the most common method for nurse practitioners to obtain
      medication for patients and 81 per cent (n=52) of nurses who have completed the
      course would continue to work under PGDs to supplement the formulary. CONCLUSION:
      It was surprising and worrying to find that less than half (n=28, 44 per cent) of
      nurse prescribers do not prescribe after completing the course. The reasons for
      this are unclear but could include: inappropriate selection of staff and problems
      accessing prescription pads, lack of peer supervision and inadequate knowledge of
      pharmacology. More studies are needed to understand the reasons and to help
      ensure government targets on increasing the numbers of nurse prescribers are met.

PMID- 15490698
TI  - Expanding student learning using patient pathways.
AB  - This article examines the first stages of a project to address problems in the
      quality of students' clinical experience after consultation with senior nurses at
      a large district general hospital. The term 'placement pathway' is defined and
      the use of these pathways is discussed. Several examples are given to demonstrate
      ways in which students can gain a wider understanding of the care of the patient
      throughout their stay and still achieve competence.

PMID- 15490699
TI  - Leg ulceration part 2: patient assessment.

PMID- 15490700
TI  - Return to the future.

PMID- 15490701
TI  - Crack down on fractures.

PMID- 15490702
TI  - Issues involved in pre-operative consent.

PMID- 15490703
TI  - Current practices and medico-legal aspects of pre-operative consent.
AB  - BACKGROUND: Written informed consent is a pre requisite for surgical intervention
      as it provides the forum for the patient to appreciate implications of the
      procedure and the doctor to explain details and effects of the surgery.
      OBJECTIVES: To evaluate the practice of obtaining informed consent pre
      operatively by surgeons in Benin City and proffer solutions that would enhance
      its practice. DESIGN: Cross-sectional study involving surgical patients or their
      relations or gurdian (in cases involving minors and unconscious patients) who
      were interviewed with structured ended questionnaires. SETTING: Study was carried
      out at the University of Benin Teaching Hospital, Benin City, between 5th July
      and 6th September 2002. RESULTS: One hundred and thirty-three respondents;
      53(39.2%) males and 80(60.2%) females were interviewed. Documentations regarding
      consent were noted in 118(88.7%) cases. Of these, 74.6% felt they had enough time
      to reflect on the consent obtained while 48(36.1%) respondents were meeting the
      individual who obtained their consent for the first time. The content of
      information offered patients prior to obtaining consent was found to be
      significantly related to the levels of education (X2= 31.44; P<0.001). Over a
      hundred respondents were not informed of risk of procedure. Nonetheless over 50%
      of respondents felt satisfied with information supplied. CONCLUSION: The quality
      of consent obtained from the average patient fell below expected standard. There
      is need for greater awareness amongst administrators of consent on the essence of
      improving quality of information given and mode of obtaining consent from
      patients.

PMID- 15490704
TI  - Hysteroscopic surgery at the Aga Khan Hospital, Nairobi.
AB  - OBJECTIVES: To determine the experience, acceptability and outcome of
      hysteroscopic surgery at the Aga Khan Hospital, Nairobi. DESIGN: A retrospective
      study. SETTING: Aga Khan Hospital, Nairobi. PATIENTS: Between May 2000 and April,
      2003, 463 cases of hysteroscopy were undertaken at the Aga Khan Hospital,
      Nairobi, of these 54 patients (11.7%) underwent various hysteroscopic surgical
      procedures. A review of these cases and their outcomes are analysed and
      presented. RESULTS: In a thirty six month period 463 cases of Hysteroscopy were
      done at the Aga Khan Hospital, Nairobi. Of these 54 cases had operative
      intervention (11.7%). The case load of diagnostic hysteroscopy increased from 50
      in the year 2000, to 206 and 159 respectively in the years 2001 and 2002. By this
      time, some consultants were performing diagnostic hysteroscopies on their own.
      The surgical procedures performed included hysterscopic retrieval of "lost"
      IUCD's, and intrauterine bone spicules and hysteroscopic resection of submucous
      fibroids (25.9% of the cases), resection of endometrial polyps (25.9%)
      hysteroscopic synechiolysis, (16.6%) and endometrial resection or ablation
      (cauterisation) (7.4%). All the patients were reviewed by the consultant pool
      after one week. Three cases of complications were encountered, two cases of
      uterine perforation and one case of fluid overload (TURP syndrome) following a
      resection of a submucous fibroid. CONCLUSION: Hysteroscopy and hysteroscopic
      surgery are the established gold standards for the management of intrauterine
      pathology. The procedures were well accepted amongst patients who had undergone
      these procedures. RECOMMENDATIONS: In Kenya, gynaecologists still have to embrace
      change and undergo adequate and sustained training in the various aspects of
      hysteroscopy, so as to make the proecdures acceptable and accessable to more
      patients.

PMID- 15490705
TI  - Quality of-life in male cancer patients at Kenyatta National Hospital, Nairobi.
AB  - BACKGROUND: The quality of life of cancer patients is likely to be influenced by
      psychological reactions of the cancer patients yet there are no documented issues
      related to quality of life in cancer patients in Kenyan hospitals. OBJECTIVE: To
      investigate issues which affect the quality of life in male cancer patients.
      DESIGN: Prospective cross sectional study. SETTING: Kenyatta National Hospital,
      Nairobi, Kenya. METHODS AND SUBJECTS: Cancer patients above 12 years of age were
      interviewed during the course of their stay in the hospital, specifically to
      gather information on; semi structured questions and a modified Beck's 24 item
      depression inventory with a view to solicit for their reaction on issues which
      pertains to quality of life. MAIN OUTCOME MEASURES: Age group, level of
      education, tribe, geographical place (province) of birth, chief complains, main
      concerns, views on doctors, contact with psychiatrist and psychologist, the
      anatomic site of cancer, treatment given and responses on modified Beck's
      depression inventory. RESULTS: Forty two patients were studied, their age range
      13-72 years, mean 43.2 and peak 13-26 years. Forty seven per cent of cases had no
      formal education. The cancers were gastrointestinal tract 33%, blood and lymphoid
      tissue (26%), bone and muscle (11.9%), skin (9.4%) and genitourinary tract
      (4.8%). Treatment given was chemotherapy, radiotherapy and surgery. Ninety three
      per cent were unable to cope. Chief complaints were pain, inability to work,
      feeling miserable and concerns were families, health and work retardation.
      Modified Beck's depression score was 20%, with major issues being; work
      retardation, insomnia, weight loss, and anorexia. Most affected were, age group
      27-35 years (and least 13-26 years), uneducated, living in Nairobi (city), having
      carcinomas, treatment with combined surgery and radiotherapy. Low education level
      and residence in Nairobi coped poorly. Radiation therapy group appeared to cope
      better than other modalities. CONCLUSION: The issues affecting the quality of
      life of male cancer patients stated were pain, inability to work, poor coping
      with cancer and psychological reactions of work retardation, insomnia, weight
      loss, fatigability and depression. Gambling, suicidal ideas and social withdrawal
      were minimal. Other concerns were families, health and work.

PMID- 15490706
TI  - Atraumatic intracutaneous skin closure with self-made fishing line suture
      compared to commercial thread.
AB  - OBJECTIVE: The aim of this study was to prove, whether the intracutaneous skin
      closure with self made fishing line suture is equivalent to commercial sutures.
      DESIGN: It was a randomised blinded animal study. SETTING: The study was
      performed in December 2002 at the Muhimbili University College of Health Sciences
      in Dar-es-salaam. SUBJECTS: Both German surgeons from Mannheim, and Tanzanian
      surgeons from Dar es salaam operated on nine one year old Tanzanian domestic
      sheep. INTERVENTIONS: 108 standardised cutaneous wounds on the backs of the
      animals were closed by intracutaneous sutures either with self produced fishing
      line suture or a commercial nylon suture (Ethilon). MAIN OUTCOME MEASURES: The
      clinical and histological outcomes, as well as the costs of this self-made
      fishing line suture, with a commercial nylon thread were evaluated and compared.
      RESULTS: There are no significant differences between the two sutures in
      histological or clinical findings, or in the reported ease of use by the
      surgeons. The cost of a self-produced atraumatic thread is US$ 0.12, less than
      one-twentieth of the cost of the commercial thread. CONCLUSION: Self-made fishing
      nylon suture has characteristics and properties in sheep skin wounds comparable
      to commercial nylon suture. The advantage of the commercial thread is the
      guaranteed quality assurance. It is discussed whether this quality assurance
      justifies the large price difference, and whether the self-produced thread should
      be recommended to surgeons in countries where the costs of surgical material
      often remains an obstacle for life saving operations.

PMID- 15490707
TI  - Prevalence of pathogenic Escherichia coli and parasites in infants with diarrhoea
      in Kumasi, Ghana.
AB  - OBJECTIVES: To determine the relative frequencies and prevalence rates of
      pathogenic Escherichia coli and intestinal parasites in hospitalised infants (0-5
      years) in Kumasi. DESIGN: A prospective descriptive study of screening 162 (83
      males and 79 females) infants with diarrhoea and 122(64 males and 58 females) non
      diarrhoeal infants controls for pathogens (E. coli and intestinal parasites) by
      standard microbiological methods. SETTING: Komfo Anokye Teaching Hospital and
      Maternal and Child Hospital, Kumasi, Ghana. RESULTS: From the 162 in the
      diarrhoeal group 96(59.6%) pathogens, and from the 122 in the control group,
      eight (6.6%) pathogens were isolated. Enteropathogenic E. coli (EPEC) was the
      most frequently detected pathogen, accounting for 24(14.8%) of the findings in
      the diarrhoeal group, five (4.1%) in the non-diarrhoeal control group. Of the 26
      EPEC isolates, there were nine serotypes with the three dominant ones being 0125
      (6), 0119 (5), and 026 (15). Other agents isolated included Ascaris lumbricoides
      18(11.1%) and two (1.6%), Cryptosporidium 13(8.0%) and one (0.8%) for diarrhoeal
      and non-diarrhoeal infants respectively. The following were detected only in
      diarrhoeal stools. Giardia lamblia, six (3.7%); Trichomonas hominis, three
      (1.9%); Trichuris trichiura one (0.6%) and hookworm, one (0.6%). CONCLUSION: From
      this study, EPEC and Cryptosporidium may be considered as important
      diarrhoeagenic pathogens and it is hoped that provision of potable water and good
      sanitation may decrease diarrhoeas in infants caused by these agents.

PMID- 15490708
TI  - Salmonellae carrier status of food vendors in Kumasi, Ghana.
AB  - OBJECTIVE: To determine the prevalence of chronic typhoidal salmonellae amongst
      food vendors in Kumasi Ghana. DESIGN: A prospective study. SETTING: Sitting and
      itinerant food vendors in Kumasi. METHODS: Screening of 258 (230 females of 28
      males) healthy food vendors for Salmonella typhi, and S. paratyphi A, B, and C,
      using stool culture, the widal test, and standard microbiological identification
      methods. MAIN OUTCOME MEASURES: Prevalence of chronic typhoidal Salmonellae
      carriers among food vendors in Kumasi. RESULTS: Typhoidal Salmonellae were
      isolated from six people, giving a carriage rate of 2.3%. Three of the
      Salmonellae isolated were S. typhi, and they had significant Widal agglutinin
      titres of > or = 1/160 and > or = 1/320 for 0 and H antigens, respectively. The
      other three were non-typhoidal Salmonellae. The three had S. typhi and the other
      three had titres of 1/80 or less for both 0 and H antigens, respectively. We have
      discussed the implications of this high carriage rate, and we have suggested the
      inclusion of screening for Salmonellae of the regular health screening exercise
      undertaken by food handlers to detect and monitor chronic carriers in the food
      industry, to help control salmonella diseases in the community. CONCLUSION: From
      our study, food handlers consitute a significant risk in the spread of enteric
      fever in Kumasi. We therefore, suggest the inclusion of screening for Salmonellae
      in the regular obligatory six-monthly examination required of food handlers and
      to monitor those found to be infected.

PMID- 15490709
TI  - Post traumatic stress disorder among motor vehicle accident survivors attending
      the orthopaedic and trauma clinic at Kenyatta National Hospital, Nairobi.
AB  - OBJECTIVES: To determine the prevalence rate of post traumatic stress disorder
      (PTSD) and associated risk factors among motor vehicle accident (MVA) survivors
      attending the orthopaedic and trauma clinic at Kenyatta National Hospital,
      Nairobi. DESIGN: A cross-sectional study. SETTING: Kenyatta National Hospital,
      Nairobi. SUBJECTS: One hundred and ninety seven adult males and sixty seven
      female patients. METHOD: The 264 patients were interviewed using a questionnaire
      to collect the socio-demographic data, the Self Rating Questionnaire (SRQ) and
      the Impact of Event Scale-Revised (IES-R). Diagnosis was made using the
      Diagnostic and Statistical Manual (DSM-IV). RESULTS: The mean age was 34.63+/
      12.71 years (range 18-65). Overall, the prevalence rate of PTSD was 13.3%. None
      of the cases had been previously diagnosed as having PTSD. Females had a higher
      rate of 17.9% (n = 67), compared to the males 11.7% (n=197). The majority of
      those with PTSD (42.9%) were young, 20 - 29 years. Other risk factors were having
      post-primary education (62.9%), experiencing the first motor vehicle accident
      (14.1%), previous psychiatric illness, and other medical illnesses. The type of
      accident, role/status and immediate reactions to the accident were not
      significant. CONCLUSIONS: PTSD following motor vehicle accidents is common.
      Although the MVA survivors do develop significant rates of PTSD, it is not easy
      to identify those at risk but some of the parameters documented in this study may
      help. A multi disciplinary approach is therefore essential in the management of
      the RTA survivors at the orthopaedic and trauma clinics if their physical and
      psychological needs are to be adequately addressed

PMID- 15490710
TI  - Morbidity and mortality of low birth weight infants in the new born unit of
      Kenyatta National Hospital, Nairobi.
AB  - BACKGROUND: Morbidity and mortality of low birth weight (LBW) infants at Kenyatta
      National Hospital (KNH) has previously been found to be high. Other centres have
      shown that even with lack of neonatal intensive care facilities, selective
      interventions can be implemented that improve neonatal survival rates. It is
      important to identify those factors at KNH that when selectively modified, will
      improve the quality of care hence survival rates. OBJECTIVE: To quantify the
      morbidity and mortality of LBW infants in KNH. To audit the quality of care and
      identify factors that can be selectively modified to improve the quality of care
      and improve the currently low survival rates. DESIGN: Retrospective study
      utilising case notes. SETTING: New born unit, Kenyatta National Hospital,
      Nairobi. SUBJECTS: All LBW infants admitted to the NBU at KNH from January to
      December 2000. RESULTS: Out of an expected 694 files, 533 (77%) were studied. The
      male to female ratio and LBW to VLBW ratio was 1:1 respectively. Small for
      gestational age (SGA) accounted for 11.6%. Overall mortality was 57.4% (574/1000
      admissions) while mortality for SGA was 37%. Infants born out of KNH had
      significantly higher mortality (p=0.0047). Compared to Caeserian delivery,
      infants born via spontaneous vertex delivery had higher mortality (p=0.0087). The
      leading diagnoses on admission or death were respiratory distress(69%), apnoeic
      attacks (42%) suspected sepsis and jaundice (37% each), hypothermia(27%) and
      anaemia(17%). By time of death or discharge, 43% had no laboratory investigations
      done. While 37% had suspected sepsis, only 14% had blood culture done.
      Antibiotics were started in 460 (86%) of infants yet only 37% had diagnosis of
      suspected sepsis. Change of antibiotics was guided by culture and sensitivity
      reports in only 62(13.5%). Apnoeic spells were managed with rectal aminophyline
      in 156(29%) infants of whom 19(12%) survived. The terminal events for the dead
      infants included recurrent apnoeic spells. The only mode of nutrition was enteric
      feeding in 59% with breast milk, formula or pasteurized cows milk by nasogastric
      tube, breast feeding or cup feeding. Except for dextrose water, parenteral
      nutrition was not utilised. Of 63 infants dying with associated anaemia, 43(68%)
      were not transfused due to lack of reliable blood supply. CONCLUSION: Compared to
      previous studies, mortality of LBW infants in KNH- NBU has increased over the
      years. Improvement in supportive care as regards nutrition, temperature
      regulation, laboratory back up and respiratory support is recommended. There is a
      place for trial of kangaroo mother care and simple continous positive airways
      pressure administration methods. There is a need to ascertain the efficacy of the
      method of aminophyline administration.

PMID- 15490711
TI  - Primary breast sarcoma: case report.
AB  - Primary breast sarcoma is a rare entity occurring in 0.5% of women with breast
      malignancy. Like in breast carcinoma, delay in its diagnosis has important
      clinical and treatment implications. The subject of this report presented at our
      breast unit with advanced breast lesion months after she noticed a small lump in
      her right breast. She had no clear diagnosis despite several consultations, in
      patient treatments at two facilities in the city, breast ultrasonography, breast
      mammography and three fine needle aspiration cytology (FNAC) examinations. The
      patient needed multiple blood transfusions. A final FNAC showed ductal carcinoma.
      Histology following wide excision confirmed high-grade primary stromal breast
      sarcoma. She required adjuvant combination chemotherapy. A combination of
      diagnostic failures and patient fault caused delay in subject's treatment. Lesion
      progression during delay which influenced the pattern of physical morbidity,
      tumour prognosis and need for adjuvant treatment. Embracing the concept of breast
      care in dedicated breast units may minimise such treatment delays.

PMID- 15490712
TI  - Primary thyroid lymphoma: report of two cases.
AB  - Primary thyroid lymphoma is a rare disease. Most of the patients have a history
      of Hashimoto's thyroiditis. Main histopathologic subtypes are either mucosa
      associated lymphoid tissue (MALT) or diffuse large cell lymphomas. Treatment
      options are surgical resection in localised, low-grade MALT lymphomas or systemic
      chemotherapy in aggressive, diffuse large cell lymphomas. But, sometimes other
      histopathologic subtypes can be seen and therapeutic approaches must be done. We
      report two patients who have primary thyroid lymphoma. There was no history of
      Hashimoto's thyroiditis in either case, and neither of them had MALT histologic
      subtype. First patient a sixty four year old woman, admitted to hospital because
      of bilateral thyroid nodules. Histological subtype was B cell follicular
      lymphoma. Subtotal thyroidectomy was performed and radiotherapy was administered
      to the entire neck region. Second patient, a 50 year old man, presented with
      complaints of a left thyroid mass and dyspnoea. Total thyroidectomy was carried
      out and chemotherapy was given. Histological diagnosis was diffuse large B cell
      lymphoma. Thyroid lymphomas had heterogenous histological and clinical
      characteristics. In localised, non-aggressive subtypes, surgical treatment must
      be considered. Postoperative chemotherapy or radiotherapy may be necessary in
      some patients.

PMID- 15490713
TI  - Metabolic syndrome disorders in urban black Zimbabweans with type 2 Diabetes
      mellitus.
AB  - OBJECTIVE: The main aim of the study was to determine the prevalence of metabolic
      syndrome disorders and their interrelations in black Zimbabwean type 2 diabetic
      patients. STUDY DESIGN: Prospective cross sectional study. SETTING: Outpatient
      diabetic clinics at Harare and Parirenyatwa tertiary hospitals. MAIN OUTCOME
      MEASURES: We recruited 109 adult diabetic subjects attending a tertiary hospital
      Diabetic Clinic. Anthropometric and metabolic parameters were measured by
      standard methods. Eighty percent of the patients were hypertensive, 32%
      dyslipidaemic, 32% obese, 50% hyperinsulinaemic, 61% had poor glycaemic control
      and 43% of the participants had the metabolic syndrome. The means of BMI and
      triglycerides were significantly different in hyperinsulinaemic versus non
      hyperinsulinaemic patients (p < 0.001 and 0.041 respectively), and diastolic
      blood pressure was significantly raised in the obese group (p = 0.043). The
      following significant associations were observed, hyperinsulinaemia with the
      metabolic syndrome (odds ratio = 3.9, p < 0.001) as well with obesity (odds ratio
      = 4.8, p < 0.001), however, only a weak association was observed between
      hypertension and hyperinsulinaemia (odds ratio = 2.5, p = 0.064). Patients
      exhibiting three metabolic disorders (dyslipidaemia, hypertension and obesity)
      were five times more likely to be hyperinsulinaemic (p = 0.025) and hypertensive
      patients were almost three times more likely to be hyperinsulinaemic. CONCLUSION:
      In comparison to their counterparts from certain ethnic groups, this urban
      diabetic population is also burdened with a variety of metabolic disorders which
      are risk factors for coronary artery disease. In this population,
      hyperinsulinaemia has a relatively weak association with hypertension and the
      relationship between obesity versus diastolic blood pressure as well as
      hypertriglyceridaemia versus serum insulin levels requires further investigation.

PMID- 15490714
TI  - Knowledge and perceptions of antenatal women towards prevention of mother to
      child transmission of HIV/AIDS in Blantyre, Malawi.
AB  - OBJECTIVES: To determine antenatal attendees' knowledge and perceptions towards
      selected aspects of prevention of mother to child transmission of HIV. SETTING:
      Five rural and six urban public health centers in Blantyre District, Malawi.
      SUBJECTS: 126 consecutive pregnant women attending antenatal clinics. DESIGN:
      Cross sectional qualitative study utilizing focus group discussions (FGDs).
      Analysis was based on content analysis. RESULTS: Knowledge about HIV/AIDS
      especially regarding causative agents of AIDS, transmission and prevention was
      generally high in all FGDs. One individual though, suggested that HIV was
      transmitted by mosquito bites and another that HIV was transmitted by being
      exposed to persistent coughing. The majority of 126 women identified HIV testing
      of pregnant women as of potential benefit and necessary for the prevention and
      control of HIV/AIDS. In most cases, the benefit mentioned for HIV testing was
      that it was good to know about one's HIV status rather than being ignorant. Other
      suggested benefits of HIV testing of pregnant women were: future family planning,
      as an incentive to reduce the number of sexual partners and to know the cause of
      the problem in case a child is failing to thrive rather than blame witchcraft.
      Male spouses were identified as both potential supporters and limiting agents
      towards pregnant women's acceptability of HIV testing. CONCLUSION: HIV testing
      among pregnant women to ensure prevention of mother to child transmission of HIV
      is a complex issue. Women consider various factors before making decisions.
      Programme planners and implementing agencies need to be aware of these issues and
      work together with women and other stakeholders in order to overcome such
      limitations.

PMID- 15490715
TI  - Production, distribution and problems experienced with health education materials
      in two districts of Mashonaland East Province, Zimbabwe.
AB  - OBJECTIVE: To identify the production, distribution and problems experienced with
      health education (HE) materials in two districts of Mashonaland East (Mash East)
      province of Zimbabwe. DESIGN: A descriptive survey conducted in the rural
      districts of Mutoko and Murewa within the Province. METHODS: The researcher
      interviewed four doctors, 30 nurses and 10 allied health workers who had been
      conveniently sampled. MAIN OUTCOMES MEASURES: The types of health education
      materials available, whether field-testing and distribution of materials had been
      done locally, the problems experienced and unmet needs. RESULTS: It was found
      that most of the HE materials were printed on paper, and that 93.2% of the health
      workers indicated that the materials had not been field-tested in their local
      areas and did not address local problems. While all the respondents commented
      that the materials were always few, 77.3% noted that the materials were in
      English. Most of the health workers (90.9%) indicated that they needed print
      materials, radio and video cassettes. All of them desired to have materials in
      the local languages and addressing local problems. It was also noted that in
      almost 73% of the health facilities, the materials were being kept in the
      storerooms. The majority of the HE materials in the two districts were print
      materials that had not been field-tested in the local areas, were not in the
      local languages, did not address the local problems and were kept in storerooms.
      Material production protocols need to be followed and the management should
      ensure that HE materials reach the intended audience.

PMID- 15490716
TI  - HIV and AIDS education in Zimbabwe: the missing ingredients in combating HIV and
      AIDS.

PMID- 15490717
TI  - Survival pattern among infants born to human immunodeficiency virus type-1
      infected mothers and uninfected mothers in Harare, Zimbabwe.
AB  - OBJECTIVES: To determine the mother-to-child transmission (MTCT) rate of HIV-1
      and to compare the survival patterns among infants born to HIV-1 infected and
      seronegative mothers. DESIGN: A two year prospective study from 1991 to 1995.
      METHODS: 345 HIV-1 infected mothers and 351 seronegative mothers and their
      infants were examined at regular intervals up to 24 months of age. RESULTS: The
      intermediate estimate of MTCT rate of HIV-1 was found to be 31.9%; (95%
      confidence interval (CI) 26.9 to 37.1). Of infants born to HIV-1 infected mothers
      17% died compared with 2% of infants born to seronegative mothers. Forty six
      (43%) of the 107 HIV-1 infected infants died compared with 16 (219%) of the 559
      uninfected infants. In a multivariate analysis, risk factors independently
      associated with infant mortality were low birth weight (hazard ratio (HR) 2.80;
      CI 1.52 to 5.13), HIV infected infant (HR 10.50; CI 5.48 to 20.15), HIV infected
      mother (HR 3.23; CI 3.17 to 15.85) and maternal death (HR 2.77; CI (1.09 to
      7.06). CONCLUSION: The estimated MTCT rate of HIV-1 is comparable with rates of
      25% to 45% reported from the African region. The poor survival of HIV-1 infected
      infants indicates the necessity for effective and comprehensive HIV/AIDS control
      strategies in Zimbabwe.

PMID- 15490718
TI  - Prescribing patterns of antimicrobial agents in private practice in Umtata,
      Eastern Cape, South Africa.
AB  - OBJECTIVE: To describe the prescription patterns of antimicrobial drugs in the
      private sector in Umtata. DESIGN: Descriptive, retrospective study. SETTING:
      Umtata Pharmacy, Umtata (a town in the Eastern Cape). MAIN OUTCOME MEASURES:
      Prescription patterns and quality of prescription indicators. METHODS:
      Retrospective analysis of all prescriptions for antimicrobial drugs between 1
      January and 31 December 2000, noting the method of payment, number of drugs, use
      of generic or brand name, and also whether or not the following were stated:
      diagnosis, dose, dosage form, dosing interval and duration of treatment. RESULTS:
      There were 2352 prescriptions, of which 57.7% were paid through medical aid;
      41.7% by cash, while 0.6% of the prescriptions had no form of payment stated.
      Only 10.4% of prescriptions used generic names exclusively; 83.2% used brand
      names alone and 6.4% had both generic and brand names. The form of payment
      apparently influenced the number of items per prescription, with the average
      number for medical aid prescriptions higher than for those paid for in cash (2.71
      vs. 2.11; p < 0.001). Of the prescriptions 12.5% had five or more drugs. The
      diagnosis was not stated in 94.3% of prescriptions, the dose and duration of
      treatment were not properly stated in 53.3% and 59.6% of prescriptions
      respectively. The dosage forms and dosing intervals were stated in 99% and 85% of
      prescriptions, respectively. The most commonly prescribed antimicrobials were
      amoxycillin, metronidazole and ketoconazole. CONCLUSION: The low rate of generic
      prescribing and the incomplete nature of many prescriptions are a cause for
      concern. Their cost implications and possible effect on the effective use of
      antimicrobial agents are discussed.

PMID- 15490719
TI  - Predictors and reference values of CD4 and CD8 T lymphocyte counts in pregnancy:
      a cross sectional study among HIV negative women in Zimbabwe.
AB  - OBJECTIVE: To identify predictors and define reference values for T lymphocyte
      subsets in HIV negative pregnant black women. DESIGN: Cross sectional study.
      SETTING: Edith Opperman Martenity Hospital, Harare, Zimbabwe. STUDY POPULATION:
      1113 HIV negative women 22 to 35 weeks pregnant registering for routine antenatal
      care. METHODS: A questionnaire was used to collect demographic and obstetric
      data. CD4 and CD8 T lymphocyte counts were determined by manual
      immunocytochemistry. Concentrations in serum, of retinol, beta-carotene,
      ferritin, folate and 1-antichymotrypsin were also measured. Multiple linear
      regression analysis was employed to identify and estimate effects of potential
      predictors. MAIN OUTCOME MEASURES: CD4 and CD8 T lymphocyte levels, demographic,
      obstetric data and micronutrient status. RESULTS: Predictors of CD4 counts were
      gestational age, serum retinol and season. CD4 counts declined by 25 (95%
      confidence interval [CI]; 11 to 40; p = 0.001) cells/L for each week's increase
      in gestation among women with low serum retinol, while low serum retinol was
      independently associated with lower CD4 counts (-127; 95% CI, -233 to 20 cells/L;
      p = 0.02) at 35 weeks gestation. The late rainy season was associated with higher
      CD4 counts (137; 95% CI, 67 to 207 cells/L; p < 0.001). CD8 counts were higher in
      women with low serum folate (87; 95% CI, 6 to 166 cells/L; p = 0.036) and were
      slightly higher in gravida 4+ compared to gravida one to three. Reference values
      of CD4 but not CD8 count and percentage markedly differed from flow cytometry
      values of pregnant and non-pregnant women in developed and developing countries
      reported in the literature, even after controlling for the differences in methods
      of T lymphocyte subset immunophenotyping. CONCLUSION: Gestational age, gravidity,
      micronutrient status and season influence T lymphocyte subset levels and need to
      be considered when designing clinical management and intervention strategies for
      pregnant women. The data underscores the need for local reference values.

PMID- 15490720
TI  - Beta-2-microglobulin in multiple myeloma.

PMID- 15490721
TI  - [Successes and problems gerontological system services of social protection of
      the population].
AB  - In analytical review is presented activity gerontological service of social
      protection of the population (social-gerontological service), on condition on
      01.01.2003, and track record of her development for 1991-2002. It Is given
      detailed feature to activity each of structures, forming this service (stationary
      institutions of the social service, social care centres, branches home service,
      day-time branches for the aged, branches acute care and others), as on country as
      a whole, so and in cut separate regions and federal areas. The reflected main
      successes and trends of the development social-gerontological service, as well as
      problems, which permit depends on relations state to senior generation.

PMID- 15490722
TI  - [Ageing and necrotic form of "unwanted" cells].
AB  - Collecting experimental data testify that cellular necrosis is the same component
      of "unwanted" cell system elimination in a metaphyte, as well as apoptosis. The
      essential role of the last in definition of rates of ageing is expressed, in
      particular, in secretion by phagocytes of the factors overwhelming inflammatory
      reactions which are rather characteristic for such illnesses as an
      atherosclerosis, a diabetes and others. Apparently, infringement of balance
      between necrotic and apoptotic forms "unwanted" cell elimination from an organism
      can be the important factor of ageing and the reason of reduction of life
      expectancy as a result of supression of renewal processes in an organism,
      occurrence and weights of development of some senile illness.

PMID- 15490723
TI  - [Evolutionary predecessors of oncogenesis and old age involution].
AB  - A hypothesis is stated explaining emergence of mechanisms of oncogenesis and old
      age involution. According to the hypothesis the destructive and proliverative
      phenomena, observed in the course of these pathological processes, emerged on the
      basis of the destructive and proliverative phenomena, assotiated with asexual
      reproduction in the Precambrian Metazoa. The evolutionary predecessor of the
      oncogenesis was semelparous asexual reproduction, and the evolutionary
      predecessor of the old age involution was desintegration of tissues associated
      with iteroparous asexual reproduction. The oncogenesis and old age involution in
      different lines of the Metazoa originated independently. Processes of the normal
      ontogenesis in the contempory primitive Invertebrates are pointed out. These are
      the evolutionary predecessors of regression of tumors and haemoblastosis. The
      importance of regressive development is discussed.

PMID- 15490724
TI  - [Functional morphology of skin ageing].
AB  - Cutaneous aging is a complex biological phenemenon, which consist of two distinct
      components--the instrinic genetically determined degenerative process and
      extrinic ageing due to exposure to the environment. Prolonged exposure to
      ultraviolet irradiation, primary exogeneous factor, resulting in the clinical and
      morphological changes known as photoageing. Alterations of the components of
      epidermis and connective tissue of the skin, associated with chronological and
      photoageing, are reviewed in the present article.

PMID- 15490725
TI  - [The role of free radicals oxidation in the deterioration of haemovascular
      homeostasis in aging].
AB  - Torty-two practically healthy subjects aged 60-80 and twenty-seven their younger
      counterparts aged 20-29 were investigated. The study involved investigation of
      interrelation between functional state of the endothelium, erythrocytes,
      platelets, and the state of free radicals oxidation indices. The results obtained
      showed the activation of free radicals oxidation processes in the group of older
      and old subjects in the decrease of antioxidant defence activity, this fact being
      corroborated by a statistically significant increase in the content of plasma
      malone dialdehyde, low level of superoxide dismutase, and the lack of adequate
      increment in catalase and glutathione in response to the increase in peroxidation
      processes. Moreover in the group of healthy older and old people, a deterioration
      of vasomotor function of the endothelium, a rise in erythrocytes and platelets
      aggregation activity, an increase in blood viscosity at various shift velocities
      were detected. The results of correlative analysis testify to the existance of
      interrelation between the deterioration of the indices of functional state of
      haemovascular homeustasis and uncompensated free radicals oxidation activity.

PMID- 15490726
TI  - [Does the liver ability to regeneration decrease with age? The dynamics of
      functional activity of mitochondria in process of the liver regeneration].
AB  - The ability of liver of 1-, 3-, 12- and 24-month rats to mass restoration, mass
      gain and activity of cell energy system from 1 to 30 days after ectomy of liver
      medial and left lateral lowels were investigated. It was shown that the old
      animals did not rebate to young ones in respect of regenerant gain and exceeded
      them with mitochondria functional activity at the early stages of regeneration (2
      24 h after operation). We detected a little lag in old rats (12 and 24 monthes)
      in comparison with 1-3 ones in rate of liver mass reset to corresponding age
      groups control level. It may be explained by the difference between young and old
      animals in strategy of organism homeostasis after ectomy of 2/3 liver mass. The
      rhythmic character of activities for the most of indices of mitochondria
      functional activity in liver regenerating up to 24 h with maximum at 2-3 h and 12
      18 h after operation was detected. The detected rhythm was typical mostly to
      mitochondria of the old animals. The high functional activity of mitochondria of
      the old animals and on the late stages of liver regeneration was shown.

PMID- 15490727
TI  - [Information conception of the control at aging].
AB  - The exchange of energy between organism and environment perhaps may be to
      describe with help "entropia"--notion of thermodynamics. Point of view
      information technologies authors suggest to use "factor of controls", which work
      with help principle of reverse biological connection. This principle may be to
      use for control aging, when complicated modulated electromagnetic (information)
      field has regulationing negative entropic component. There are three principles
      of information control. All principles have on the basis of utilization by
      quantitative exponents of functional asymmetry.

PMID- 15490728
TI  - [Gerontology and physico-chemical dietology].
AB  - The thermodynamic theory of biological evolution and aging of living beings makes
      it possible to propose the individual anti-aging diets on the basis of physical
      chemical estimations. In some cases it is possible to recommend the special drugs
      and dietary supplements against the different diseases too.

PMID- 15490729
TI  - [The pineal gland's peptides factors and the rhythms of functions of the thymus
      and bone marrow in animals during aging].
AB  - It was investigated the influence of pineal peptides on the aging changes both
      circadian rhythm of thymic serum factor (FTS) titer in male rats Wistar and
      circannual rhythms of FTS, the amount of stromal cells-precurcors (CFC-F),
      granulocyte-macrophage cells-precurcors (CFC-GM), CD4+, Mac-1+ and CD19+-cells in
      bone marrow of male mice CBA. Epithalamin was injected chronically beginning from
      6 month in rats and 4 month in mice. In old animals the rhythmical disturbancers
      of the indices characterized by loss of fluctuations, displacement of seasonal
      acrophase, increased or diminished amplitude, inversion of rhythm and
      desynchronization. After epithalamin injections in rats of 11, 17, 27 months the
      FTS titer at night increased and in old mice of 23-24 months appeared the peak of
      hormone level in summer-autumn, restored the difference between the amount of
      CD4+, Mac-1+-cells in bone marrow in spring and autumn, increased CFC-GM amount
      in spring, diminished CFC-F in autumn and increased this indice in winter.
      Epithalon also diminished of CFC-GM and CFC-F amount in old mice in autumn. The
      retarding age-related disturbances of suprachiasmaticus nucleus of hypothalamus
      structure, the diminishing corticosterone and testosterone levels at night, the
      increasing hormones level in summer and the falling in winter plays role in the
      improvement of thymus and bone marrow rhythmical function in old animals,
      reseaved epithalamin. The rhythms of most indices rhythms in old animals showed a
      pattern of adult.

PMID- 15490730
TI  - [Effect of epitalon on the immunity and hemostasis in hypophysectomized chicken
      and old hens].
AB  - Neonatal hypophysectomy in chicken, as well as that in old hen has been
      established to entail in 1,5 months after surgery cellular and humoral immunity
      disturbances, pronounced hypercoagulation and fibrinolysis depression.
      Administration of Epitalon (Ala-Glu-Asp-Gly) to a large extent eliminates
      revealed shifts. This effect appeared to be stronger in neonatally
      hypophysectomized chicken than in old hens.

PMID- 15490731
TI  - [Dementia and psychotic disorders in parkinsonism: common origin and new
      perspectives in therapy].
AB  - In this article, we reviewed and analysed the literature of mechanism of
      cognitive and psychotic disorders in schizophrenia, dementia and Parkinson's
      disease. Despite of opposite neurotransmitter disturbances in schizophrenia and
      Parkinson's disease, there is common origin in development of psychotic symptoms.
      The main risk factors in producing psychotic symptoms are age, cognitive
      impairment and general disease severity. The key neurotransmitter disturbance of
      dementia is hypofunction of glutamatergic and cholinergic transmitter systems. An
      hypofunction of the NMDA glutamate receptors can produce excessively stimulation
      corticolimbic dopaminergic and serotonergic neurons and appearance of psychosis.
      We suggest glutamate NMDA receptors can modulate activity of dopaminergic,
      serotonergic and cholinergic transmitter systems. Successful pharmacological
      approaches in therapy of cognitive and psychotic disorders in Parkinson's disease
      may be normalization conditions of glutamatergic and cholinergic transmitter
      systems.

PMID- 15490732
TI  - [Severe bronchial asthma in elderly patients].
AB  - Cytological and oxidative characteristics of bronchial inflammation before and
      after treatment were studied in 35 elderly patients with severe bronchial asthma
      (BA). Revealed cytooxidative particularities may be used as additional diagnostic
      and treatment efficacy markers in elderly patients with severe BA.

PMID- 15490733
TI  - [Arterial hypertension intraoperative management in aged patients by different
      premedication variants].
AB  - Problem of clofellinum (clonidine) usage in premedication in aged persons with
      arterial hypertension is discussed. Clofellinum usage may be effective of
      prevention of intraoperative hypertensive reactions in abdominal surgery.
      Clofellinum is usefull component of premedication especially in patients with non
      cared arterial hypertension and in the case of its usage as permanent non
      hypertensive drug. The patients with good-controlled arterial hypertension are
      needed in prolonged hypotensive therapy during preoperative period.

PMID- 15490734
TI  - [Peculiarities of diurnal profile of arterial blood pressure in clinically
      healthy elderly persons].
AB  - The diurnal profile peculiarities in normotensive elderly persons have been
      shown. The variability ranges of systolic arterial blood pressure are discussed.

PMID- 15490735
TI  - [Partial revascularization of the myocardium in geriatric patients with different
      forms of coronary artery disease].
AB  - Coronary artery disease (CAD) is one of the most frequent diseases of geriatric
      patients, which substantially deteriorates the quality of life and leads to
      lethal outcomes. Coronary angioplasty (CA) is an effective method of CAD
      treatment in this group of patients. CA is the method of choice for geriatric
      patients with contraindications for surgical revascularization. No consensus
      about revascularization volume in multivessel disease has been reached in the
      worldwide practice. Peculiarities of myocardial blood supply in elderly patients
      allow partial revascularization with good periprocedural and long-term results.

PMID- 15490736
TI  - [The study of peptide effect in the mechanisms of angiogenesis and forming of
      microenvironment of the tumors in old rats].
AB  - The experiments were performed in rats with transplanted sarkoma M-1. The
      injections of synthetic peptide vilon at the doses 0.5 mcg sigificantly increased
      the apoptosis of tumor cells in the experiment as compared to the control group.
      So vilon has possessed the oncomodulating action on the transplanted carcinoma.
      The injections of epigene lead to the inhibition of the sarcoma growth due to the
      development of the hemorragic necrosis and apoptosis increased. The results
      obtained suggested that vilon and epigene are the perspective preparates in the
      cancer therapy.

PMID- 15490737
TI  - [SAM (Senescence Accelerated Mice) as a model for studying the ageing and age
      associated diseases (from II Int. Meeting "Modern Problems of Gerontology and SAM
      as an aging model", July 21-23, 2003, Sapporo, Japan)].
AB  - Among several models of aging and age-associated diseases SAM is one of the most
      appropriate one, which provides studying the mechanisms of aging being not
      interfered with adaptation processes. SAM model was created by T. Takeda et al.
      around 80th of the previous century by brother/sister mating. The line is
      characterized by sufficiently shortened life-span (till 1 year) and several aging
      features like osteoporosis (SAMP6), memory and learning deficit (SAMP10),
      neurodegenerating diseases (SAMP3). All these defects are based on the
      disordering of oxidative metabolism, disturbing to some extent their metabolism.
      In short review possible reasons of such deviations in SAM metabolism are
      discussed focused during II International Meeting on modern problems of
      gerontology being hold on Sapporo between July 21-23, 2003.

PMID- 15490738
TI  - Diagnostic utility of the Learning Disability Index.
AB  - The Learning Disability Index (LDI) is one of many diagnostic indicators proposed
      for the identification of students with learning disabilities that relies on
      patterns of performance on cognitive tests. The LDI is hypothesized to relate to
      students' specific neuropsychological deficits. The present study investigated
      the diagnostic utility of the LDI with the third edition of the Wechsler
      Intelligence Scale for Children by comparing students previously diagnosed with
      learning disabilities (n = 2,053) to students without learning disabilities (n =
      2,200). Subsamples of youth with specific reading (n = 445) and math (n = 168)
      disabilities permitted further assessment of the efficacy of the LDI. Receiver
      operating characteristic (ROC) curves revealed that the LDI resulted in a correct
      diagnostic decision only 55% to 64% of the time. These results demonstrate that
      the LDI is not a valid diagnostic indicator of learning disabilities.

PMID- 15490739
TI  - Parent-, teacher-, and self-rated motivational styles in ADHD subtypes.
AB  - The motivational styles of 25 children with attention-deficit/hyperactivity
      disorder, combined type (ADHD/C), 13 children with ADHD, inattentive type
      (ADHD/IA), and 25 nondiagnosed controls (NC) were compared using parent, teacher,
      and self-ratings. Both ADHD subtypes demonstrated motivational impairment
      characterized by a preference for easy work, less enjoyment of learning, less
      persistence, and a greater reliance on external than on internal standards to
      judge their performance relative to NC. Some motivational style differences
      between ADHD subtypes were also revealed, with the ADHD/C group more motivated by
      competitiveness and a desire to be perceived as superior to others and the
      ADHD/IA group less uncooperative and possibly more passive in their learning
      styles. When IQ was statistically controlled, these results were generally
      unchanged. The contributing role of motivational deficits to the generally poor
      academic functioning of children with ADHD is discussed, along with potential
      intervention implications of the divergent motivational styles of different ADHD
      subtypes.

PMID- 15490740
TI  - The relationship between intelligence and performance on the test of variables of
      attention (TOVA).
AB  - The present study explored the relationship between the intelligence of young
      adults and their performance on the Test of Variables of Attention (TOVA). The
      study also examined whether significant differences existed between adults with
      and without attention-deficit/ hyperactivity disorder (ADHD) on TOVA errors of
      omission, errors of commission, mean correct response time, and variability, as
      well as on performance on the freedom from distractibility (FD) factor on the
      Wechsler Adult Intelligence Scale-Revised (WAIS-R). Seventy-nine adults
      participated in the study, including 17 with ADHD and 62 college students without
      ADHD. Pearson product-moment correlations indicated that none of the correlations
      between Full Scale IQ (FSIQ) and TOVA variables were significant. Analysis of
      variance results revealed that adults with ADHD made more errors of omission on
      the TOVA than did controls. Between-group differences were not found on the
      remaining dependent variables.

PMID- 15490741
TI  - Using semantics, grammar, phonology, and rapid naming tasks to predict word
      identification.
AB  - This study investigated the relative importance of semantic, grammatical,
      phonological, and rapid naming abilities in predicting word identification in a
      large, representative sample of children enrolled in first through sixth grade,
      using correlation, factor analysis, multiple regression, and predictive outcome
      analysis techniques. Composite measures of these abilities were found to
      correlate significantly with word identification, even after controlling for the
      effects of nonverbal intelligence. Factor analysis indicated that the spoken
      language composites and the word identification composite loaded on one factor,
      whereas the perceptual speed composites loaded on a second factor. Multiple
      regression analyses showed that among younger children in the early stages of
      learning to read and children whose word identifying skills were below average,
      the phonology and rapid naming composites accounted for the most variance in
      predicting word identification skills. Among older children and children who were
      proficient in word identification, the semantics composite accounted for the most
      variance. The most important analyses in this study (i.e., the calculations of
      the sensitivity indexes, the specificity indexes, and the positive predictive
      values) evaluated the practical value of using the composites to predict poor
      word identification skills in children. To be considered practically useful, all
      predictive outcome values had to be .75 or greater. None of the composites
      studied, including an application of the double-deficit hypothesis, met this
      criterion. The results from this study question the accuracy and utility of using
      any of the abilities studied to predict which students are at risk for or have
      poor word identification skills.

PMID- 15490742
TI  - Sound-symbol learning in children with dyslexia.
AB  - This study evaluated the effect of sound-symbol association training on visual
      and phonological memory in children with a history of dyslexia. Pretests of
      phonological and visual memory, a sound-symbol training procedure, and
      phonological and visual memory posttests were administered to children with
      dyslexia, to children whose dyslexia had been compensated through remedial
      training, and to age- and reading level-matched comparison groups. Deficits in
      visual and phonological memory and memory for sound-symbol associations were
      demonstrated in the dyslexia group. For children with dyslexia and children whose
      dyslexia had been remediated, the sound-symbol training scores were significantly
      associated with word and pseudoword reading scores and were significantly lower
      than those of the comparison groups. Children with dyslexia and children whose
      dyslexia had been compensated showed significantly less facilitation of
      phonological memory following the training than did typical readers. Skilled
      readers showed some reduction in accuracy of visual memory following the
      training, which may be the result of interference of verbalization with a
      predominantly visual task. A parallel decrease was not observed in the children
      with dyslexia, possibly because these children did not use the verbal cues.
      Children with dyslexia and children whose dyslexia had been compensated seemed to
      have difficulty encoding the novel sounds in memory. As a result, they derived
      less phonological memory advantage and less visual memory interference from the
      training than did typical readers. Children in the compensated dyslexia group
      scored lower on sound-symbol training than their age peers. In other respects,
      the scores of these children were equivalent to those of the typically reading
      comparison groups. Children in the compensated dyslexia group exhibited higher
      phonological rehearsal, iconic memory, and associative memory scores than
      children in the dyslexia group. Implications for the remediation of dyslexia are
      discussed.

PMID- 15490743
TI  - Understanding the relations between RAN letter subtest components and word
      reading in first-grade students.
AB  - First-grade students (N = 221) were individually tested on a battery of cognitive
      and achievement measures of verbal fluency, visual attention, phonological
      awareness, orthographic recognition, rapid automatized naming (RAN) of letters
      and objects, and reading. All tests were subjected to postacquisition scoring,
      and all RAN measures were segregated into measures of articulation time, pause
      time, and consistency of the pause time. Structural equation modeling
      demonstrated that word reading was directly and significantly predicted by RAN
      letter naming and general RAN cognitive processing time of objects. Moreover, RAN
      letter reading constructs were significantly and directly predicted by the latent
      variables of phonological awareness, orthographic recognition, and general RAN
      object articulation and cognitive processing times. RAN letter naming constructs
      were also significantly and indirectly predicted by visual attention. The reading
      model was found to be consistent with a total mediation of the relation of
      phonological awareness and reading through RAN letter naming and supported the
      validity of the RAN letter naming subtest as a basic letter reading test. These
      findings supported the double-deficit hypothesis for letter reading. We suggest
      that phonological memory is a basic factor underlying general RAN cognitive
      processing time of objects and domain-specific information associated with
      phonemes and their graphic representations.

PMID- 15490744
TI  - Wage differentials between college graduates with and without learning
      disabilities.
AB  - Wage differential studies examining legally protected groups typically focus on
      gender or racial differences. Legislation also fully protects individuals with
      learning disabilities (LD). This article is the first to decompose wage
      differentials between adults with and without LD. An original data set of college
      graduates with documented LD was constructed, and these individuals were compared
      to a control group from the National Longitudinal Survey of Youth (NLSY). Our
      results show that much of the observed lower wages for individuals with LD is due
      to differences in productivity characteristics. However, there is an unexplained
      portion of the wage gap that could possibly be considered wage discrimination
      against individuals with LD. This possibility seems smaller due to the fact that
      the subsample of the employers who knew of the employee's learning disabilities
      did not appear to pay significantly lower wages to these individuals. Alternative
      hypotheses are discussed, as are sample-specific issues.

PMID- 15490745
TI  - Depressive symptoms in and type of classroom placement for adolescents with LD.
AB  - This study investigated the relationship of depressive symptomatology to type of
      classroom placement in a sample of adolescents with learning disabilities who
      attended an urban public high school. Fifty-two students, half of whom were in
      self-contained classrooms and half of whom were in general education classrooms
      with resource room, self-rated their depressive symptoms. Their guidance
      counselors also rated these students' depressive symptoms. Self-ratings of
      depression did not differ depending on classroom placement. Guidance counselors
      rated students with learning disabilities who were in general education
      classrooms as more depressed than students placed in self-contained classes.

PMID- 15490746
TI  - Myxobolus goensis n. sp. (Myxozoa, Myxosporea, Myxobolidae), a parasite of the
      gills of Mugil cephalus (Osteichthyes, Mugilidae) from Goa, India.
AB  - Two species of Myxobolus are reported from the gills of Mugil cephalus collected
      at Goa, India: M. goensis n. sp. and M. parvus Shulman, 1962. Myxobolus goensis
      n. sp. forms digitiform or rounded plasmodia between the gill rakers. Their
      spores are oval in frontal view, with tapered anterior extremity, and lemon
      shaped in lateral view, measuring 9.7 (9.5-10.5) microm in length, 6.6 (6-7.5)
      microm in width, and 5.2 (5-6) microm in thickness. The polar capsules are
      pyriform and unequal in size. The larger ones are 5.3 (4.5-6) microm long and 2.4
      (2-3) microm wide; the smaller ones are 2.4 (2-3) microm long and 1.8 (1.5-2)
      microm wide. The polar filament forms five turns aligned perpendicularly to the
      longitudinal axis of the larger polar capsules. Within the smaller polar capsules
      the polar filament is difficult to observe and, apparently, forms three coils.
      The spores are distinctly different from other Myxobolus species infecting M.
      cephalus and other Mugil spp. Furthermore, the present material is also different
      from 204 Myxobolus species presenting differently sized polar capsules,
      representing nearly all the known species with this characteristic. The fact that
      only the M. cephalus specimens were infected among a sample of 206 fish
      specimens, comprising 27 different species, strongly suggests that this parasite
      is specific to M. cephalus.

PMID- 15490747
TI  - [Two new species of fleas from Chile and Argentina(Insecta-Siphonaptera:
      Stephanocircidae and Rhopalopsyllidae) and raising of a new sub-genus of
      Plocopsylla Jordan, 1931].
AB  - A new subgenus of Plocopsylla is raised, Schrammapsylla Beaucournu and Menier
      from the entire group B of Schramm & Lewis, 1988 and two new fleas from Chile and
      Argentina are described: Plocopsylla (S.) muruai n. sp. Beaucournu and Gallardo
      and Ectinorus (E.) mimacydis n. sp. Beaucournu and Gallardo. These two taxa are
      only known by the male sex.

PMID- 15490748
TI  - [Description of three new species of Paractenopsyllus genus (Siphonaptera:
      Leptopsyllinae) from Madagascar].
AB  - The males of three new and rare species of the Malagasy endemic genus
      Paractenopsyllus Wagner, 1938 are described. Paractenopsyllus beaucournui, P.
      oconnori and P. raxworthyi have been collected on endemic small mammals and the
      black rat. As for others species of the genus, biotopes are rain-forests of the
      central highlands or the northern mountains of Madagascar. Two of the described
      species were collected at elevations lower than typical for the genus and below
      the limits of the highland bioclimatic zone. Morphological affinities between
      these new species and those already described provide taxonomic framework for the
      genus. An updated identification key is provided for the diagnosis of all the 20
      Malagasy species of Leptopsyllinae.

PMID- 15490749
TI  - [Phlebotomus from Madagascar (Diptera: Psychodidae). III--Description of
      Phlebotomus (Anaphlebotomus) fontenillei n. sp].
AB  - The male of Phlebotomus (Anaphlebotomus) fontenillei n. sp. is described from
      Namoroka area (Madagascar). Its belongs to the subgenus Anaphlebotomus: style
      with four spines, coxite without basal process and paramere with two branches. It
      shares with P. berentiensis an original and exclusive antennal formula: 2/III-XII
      which distinguishes them from P. fertei. P. fontenillei n. sp. differs mainly
      from P. berentiensis by about 40 setae in tuft on the ventral face of the coxite,
      the length of the genital ducts and the position of the spines on the style.
      Sequence of the second internal transcribed spacer (ITS2) of the ribosomal DNA
      (rDNA) is very informative: the male of P. fontenillei n. sp. cannot be linked to
      the female of P. huberti (male unknown) regarding the size of amplified DNA
      fragment (459 bp versus 600 respectively) and the high degree of variability.
      There are few differences (10 mutations) between the sequences of P. fontenillei
      n. sp. and P. berentiensis which are closely related species.

PMID- 15490750
TI  - North Spain (Burgos) wild mammals ectoparasites.
AB  - Twenty-seven species of arthropods were collected from 105 wild mammals, six
      wolves Canis lupus (Linnaeus, 1758) included. A total of 87 animals (82.8%)
      harboured some ectoparasites. Ticks were found in 60% of the samples, fleas in
      51.4%, chewing-lice in 3.8%, and others (Mesostigmata and hippoboscids) in 3.8%.
      Moreover, 42.5% were single infestation and 57.5% mixed. Some of the species were
      new records for a host in spanish country such as Trichodectes canis (De Geer,
      1778), Ixodes trianguliceps (Birula, 1895), Ceratophyllus (Monopsyllus) S.
      sciurorum (Schrank, 1803) and Paraceras melis melis (Walker, 1856) on several
      mammals. Two species were new records for Spain: Chaetopsylla matina (Jordan,
      1925) and Archaeopsylla erinacei erinacei (Bouche, 1835).

PMID- 15490751
TI  - Activity of Lutzomyia pseudolongipalpis and L. longipalpis s.l. (Diptera:
      Psychodidae) in Venezuela.
AB  - The nocturnal activity of the phlebotomine sandfly Lutzomyia pseudolongipalpis
      and two populations of L. longipalpis s.l. from different American visceral
      leishmaniasis foci in Venezuela was studied using collection bottle rotator
      traps. The activity of L. pseudolongipalpis from Lara State was continuous
      throughout the night, while that of L. longipalpis s.l. from El Layero, Guarico
      State and from Santa Ana del Valle, Margarita Island, was greatest before 23:00
      h. The activity of sandflies of both populations and sexes steadily decreased
      thereafter. These different patterns seem to correlate with genetic data that
      indicate the presence in Venezuela of at least two sibling species in the L.
      longipalpis complex. The advantages of the bottle rotator trap for this type of
      study are discussed.

PMID- 15490752
TI  - About the presence of Phlebotomus sergenti Parrot, 1917 (Diptera: Psychodidae) in
      Eastern Sicily, Italy.
AB  - The note reports the data of a three-year sand fly investigation (1997-99)
      carried out in Eastern Sicily (Italy) with the aim to study the distribution of
      Phlebotomus sergenti. The survey involved a densely inhabited area at the foot of
      Mount Etna and the area of Iblei mounts. A total of 9,095 sand flies, of which
      63.4% males, were captured. Five species belonging to the genus Phlebotomus (P.
      perniciosus, P. perfiliewi, P. neglectus, P. sergenti and P. papatasi) and one to
      the genus Sergentomyia (S. minuta) were identified. Both the prevalence and
      distribution of the species were different within the two areas studied. In Mount
      Etna area, P. perniciosus (77.7%) was the prevalent species followed by S. minuta
      (19.8%), P. sergenti (2.0%), P. neglectus (0.3%) and P. papatasi (0.2%). While in
      Iblei mounts region S. minuta (84.5%) showed the highest prevalence, followed by
      P. perniciosus (14.4%), P. perfiliewi (0.9%) and P. neglectus (0.1%). Here, P.
      sergenti was a very rare species (< 0.02). P. sergenti was mostly associated to
      domestic habitats of peri-urban and urban zones located between two and 750 m
      a.s.l. The density values of P. sergenti, expressed as number of specimens/m2 of
      sticky trap, were between 0.3 and 5.5 with the highest value in the hilly
      collecting sites. The low observed abundance of P. sergenti does not allow to
      draw any prediction on the role that the species could play in the transmission
      of leishmaniasis in Sicily.

PMID- 15490753
TI  - Zoonotic onchocerciasis caused by a parasite from wild boar in Oita, Japan. A
      comprehensive analysis of morphological characteristics of the worms for its
      diagnosis.
AB  - Histological examination of a nodule removed from the back of the hand of a 58
      year-old woman from Oita, Kyushu, Japan showed an Onchocerca female sectioned
      through the posterior region of the worm (ovaries identifiable) and young (thin
      cuticle). Six Onchocerca species are enzootic in that area: O. gutturosa and O.
      lienalis in cattle, O. suzukii in serows (Capricornis crispus), O. skrjabini and
      an Onchocerca sp. in Cervus nippon nippon, and O. dewittei japonica in wild boar
      (Sus scrofa leucomystax). Diagnostic characters of female Onchocerca species,
      such as the cuticle and its ridges, change along the body length. Tables of the
      histologic morphology of the mid- and posterior body-regions of the local species
      are presented. In addition, it was observed that transverse ridges arose and
      thickened during the adult stage (examination of fourth stage and juvenile
      females of O. volvulus). The specimen described in this report, with its
      prominent and widely spaced ridges, was identified as O. d. japonica. Four of the
      10 zoonotic cases of onchocerciasis reported worldwide were from Oita, three of
      them being caused by O. d. japonica, the prevalence of which in local wild boar
      was 22 of 24 (92%).

PMID- 15490754
TI  - The effects of concurrent experimental infections of sheep with Trichostrongylus
      colubriformis and T. vitrinus on nematode distributions, numbers and on
      pathological changes.
AB  - Simultaneous infections of Trichostrongylus colubriformis and T. vitrinus in the
      small intestine of the sheep were examined by comparing the numbers of worms
      which established and their distribution within the intestine in both
      monospecific infections and mixed infections. The results differed depending upon
      the species and number of parasites. The establishment of T. colubriformis was
      reduced and the distribution of the nematode population was displaced posteriorly
      within the intestine when 30,000 larvae of both species were administered,
      compared with pure infections of T. colubriformis. The reduced establishment was
      less marked with infections of 15,000 larvae of both species and there was only a
      slight posterior displacement of T. colubriformis. Neither effect was evident
      with infections of 7,500 larvae of both species. The rate of establishment and
      distribution of T. vitrinus were unaffected by the presence of T. colubriformis
      at all three rates of infection. Atrophy of villi and hypertrophy of crypts
      occurred at the main site of infection in the anterior duodenum. The severity of
      villus atrophy was related to the number of infective larvae administered and/or
      the worm burden. In the ileum, beyond the main site of infection, hypertrophy of
      villi was only found in sheep receiving the greatest number of infective larvae.

PMID- 15490755
TI  - Frenkelia parasites in a small mammal community. Dynamics of infection and effect
      on the host.
AB  - A community of small mammals, Clethrionomys glareolus, Arvicola terrestris,
      Microtus arvalis, M. agrestis, M. subterraneus, Apodemus spp. and Sorex spp., was
      studied as hosts of Frenkelia glareoli and F. microti in Fronche-Comte (France).
      They were monitored in spring, summer and autumn on an area of about 1,350 ha
      comprising open field, hedgerow network and forest. Among 1,714 small mammals
      examined between July 1992 and October 1993, 47% (178/376) of C. glareolus, 9.9%
      (14/139) of A. terrestris and 1.3% (4/311) of Apodemus spp. were infected by F.
      glareoli. The prevalence of infection with F. microti was 9.2% (66/716) in M.
      arvalis and 8.2% (6/73) in M. agrestis. M. subterraneus and Sorex spp. were not
      infected. The maintenance of each parasite in a rural landscape is assured both
      by a forest and a grassland host. Multiple logistic regression showed that
      prevalence was highly age-dependent, with an apparent seasonal pattern.
      Prevalence varied between 30% in summer and 60% in early spring for F. glareoli
      in C. glareolus and between 3% in autumn to 30% in early spring for F. microti in
      M. arvalis. The year, habitat, host sex, relative density had no impact on
      prevalence. In M. arvalis only, sexually active voles were preferentially
      uninfected, indicating a possible impact of this parasitism on fertility.

PMID- 15490756
TI  - Parasites of Columba livia (Aves: Columbiformes) in Tenerife (Canary Islands) and
      their role in the conservation biology of the laurel pigeons.
AB  - The prevalence and intensity of the parasites from 50 wild doves (Columba livia)
      from the city of Santa Cruz de Tenerife, in the island of Tenerife (Canary
      Archipelago), were studied. The following ectoparasites were found in apparently
      healthy pigeons (prevalences are shown in percentage (%) and mean intensities
      with their standard deviations): the acari Dermanyssus gallinae (De Geer, 1778)
      (6, 241.0 +/- 138.9) and Tinaminyssus melloi Fain, 1962 (10%, 218.3 +/- 117.3);
      the louses, Columbicola columbae Linnaeus, 1758 (100%, 111.4 +/- 76.8) and
      Campanulotes bidentatus Scopoli, 1763 (94%, 48.4 +/- 26.6); and the pigeon fly,
      Pseudolynchia canariensis Macquart, 1839 (36%, 6.2 +/- 1.6). The endoparasites we
      found were: a haemoprotozoan species, Haemoproteus columbae Kruze, 1890 (82%,
      14.8 +/- 10.3 per 1000); coccidian oocysts, Eimeria sp. (50%, 0.2 x 10(3) +/- 1.7
      x 10(3) per gr); a cestode species Raillietina micracantha (Fuhrmann, 1909) Lopez
      Neyra, 1947 (44%, 12.3 +/- 9.4); and four nematode species, Tetrameres
      (Tetrameres) fissispina (Diesing, 1861) Travassos, 1915 (4%, 99.5 +/- 34.1),
      Synhimantus (Dispharynx) spiralis (Molin, 1858) (8%, 46.8 +/- 11.6), Ascaridia
      columbae (Gmelin, 1790) Travassos, 1913 (40%, 8.4 +/- 8.8) and Aonchotheca sp.
      (18%, 6.0 +/- 3.1). Several species detected in our study can be pathogens for C.
      bollii and C. junoniae, which are endemic pigeons of the Canary Islands,
      considered endangered species. Parasites (ectoparasites, protozoa and helminths)
      of C. livia found in Tenerife and others from wild and farm birds in the island
      were considered as healthy controls.

PMID- 15490757
TI  - Plasmodium falciparum hyperparasitaemia in children. Risk factors, treatment
      outcomes, and gametocytaemia following treatment.
AB  - The risk factors associated with hyperparasitemia at presentation and after
      treatment with different antimalarial drug regimens were evaluated in 1,048
      children enrolled prospectively in seven antimalarial drug trials between July
      1996 and September 2003 in a hyperendemic area of southwestern Nigeria. The
      outcomes of treatment of hyperparasitaemia, and gametocyte carriage following
      treatment were also evaluated. The children were assigned to one of seven
      treatment groups: chloroquine (CQ) only; pyrimethamine-sulfadoxine (PS) only;
      amodiaquine (AQ) only; CQ plus chlorpheniramine (CQCP); PS combined with CQ or AQ
      (COM); PS combined with probenecid (PPS); and halofantrine (HF).
      Hyperparasitaemia was found in 100 (9.5%) of the 1,048 children at enrolment (day
      0). Following oral therapy, 1.2% of all patients (i.e. 13 patients) became
      hyperparasitaemic, which developed in all patients by day 1 of follow-up. In a
      multiple regression model, age < or = 5 years, and a core temperature (oral or
      rectal) > or = 39.5 degrees C were found to be independent risk factors for
      hyperparasitaemia at enrolment. Following therapy, the cure rate on day 14 was
      significantly lower in those treated with CQ compared to other treatment groups.
      Severe resistance (RIII) response to treatment occurred significantly more
      frequently in those with hyperparasitaemia at enrolment than in those without,
      and was seen in five and one child with hyperparasitaemia who were treated with
      CQ and CQCP, respectively. Gametocyte carriage was insignificantly lower at
      enrolment and at all times following treatment in children with hyperparasitaemia
      than in age- and gender-matched children without hyperparasitaemia who received
      the same treatment. The results are discussed in the light of management of
      uncomplicated hyperparasitaemia in children in endemic settings.

PMID- 15490758
TI  - Efficacy of artemether-lumefantrine treatment in patients with acute
      uncomplicated Falciparum malaria in Mayotte, a French collectivity of the Comoros
      Archipelago.
AB  - Mayotte is a French island located in the Comoros archipelago in the Indian
      Ocean. Due to the high level of resistance to chloroquine and sulfadoxine
      pyrimethamine in this area, new therapeutic strategies are required. The aim was
      to assess and to document the efficacy of artemether-lumefantrine (AL)
      combination in four oral dosages. The follow-up was carried out during 21 days to
      monitor the antimalarial drug efficacy in an open trial in April-May, 2002.
      Results were obtained from 51 patients, aged from three to 46 years (12% less
      than five years). No case of therapeutic failure was observed. At day 2 after
      treatment, all the patients were apyretic and none of them had parasitaemia until
      day 21. This first therapeutic trial of the AL combination in the Indian Ocean
      sub-region shows that this association is safe, effective and rapid. AL should be
      an alternative treatment of uncomplicated malaria attacks in Comoros Archipelago,
      and will be of help to manage imported chloroquine-resistant falciparum malaria
      strains in Madagascar.

PMID- 15490759
TI  - [A new morphological character for the identification of Stomoxys calcitrans and
      S. niger (Diptera: Muscidae). Comparison of La Reunion island populations].
AB  - On La Reunion Island (France), two morphological closely related species of
      stable flies (Diptera: Muscidae), living in the same environment, Stomoxys
      calcitrans and S. niger, are involved in the transmission of blood parasites to
      the livestock. To facilitate a rapid identification of both species in the field
      conditions, we highlighted a diagnostic morphological character not yet
      described: the length of the maxillary palpus. The study of three populations of
      S. calcitrans and two populations of S. niger, collected at various elevations,
      showed that the maxillary palpi of S. niger were significantly longer than in S.
      calcitrans, independent of sex. This character, easily visible in the field with
      a simple magnifying glass, has been confirmed on individuals of both species from
      West Africa.

PMID- 15490761
TI  - [Psychotherapeutic medicine].

PMID- 15490760
TI  - Early events in the life cycle of the mouse coccidium Eimeria falciformis (Eimer,
      1870) Schneider, 1875 in naive and immune hosts.
AB  - The initial phases of invasion of mammalian coccidia of the genus Eimeria into
      host tissue are still poorly known. This process, including the passage of
      oocysts through the intestinal lumen, excystation of sporozoites, their
      penetration into epithelial cells and migration to the target site was studied in
      both naive and immune mice infected with Eimeria falciformis. After oral
      infection, the intact oocysts were transported with enteral contents to the large
      intestine, where the excystation of sporozoites and their penetration into
      superficial epithelium took place. The sporozoites subsequently migrated into the
      epithelium of crypts, which is the specific site of asexual multiplication. The
      immune status of the hosts did not affect the passage of oocysts, excystation and
      penetration of sporozoites. However, the migration of sporozoites towards their
      target site (crypts) was impeded in immune mice and sporozoites tended to remain
      in superficial mucosa rather than migrate to the crypts.

PMID- 15490762
TI  - [Psychosomatics, psychotherapy and neuronal plasticity--how words change our
      mind].
AB  - Certain psychosomatic disorders such as chronic psychosomatic pain, phobias and
      other anxiety disorders as well as depression are often stress-related but may
      also be acquired by learning associated with traumatic experience. As learning is
      based on changes in neuronal networks, the brain will be altered in these
      diseases. In turn, brain structure and function may also be influenced and even
      changed by effective psychotherapy as well as by other (behavioural) cognitive
      interventions--words and thoughts--when leading to cognitive restructuring. Due
      to their neuronal plasticity our brains are capable of constantly rewiring
      themselves so that we can--in Andreasen's words--"literally change our mind".

PMID- 15490763
TI  - [The old person--a trouble patient?].
AB  - Persons well advanced in years suffer from constantly increasing polypathia, loss
      of performance and loss of functions. At the same time the demands of an ever
      more quickly changing society grow. Society hardly cares for the elderly, the
      handicapped and disabled. Often, these people are regarded as a burden, a fact
      that they are very well aware of. When the usual patterns of communication fail,
      physicians may become impatient and are, as a consequence, perceived as
      intimidating and indifferent by the patient. In this way the physician initiates
      a vicious circle, which often leads to a complete failure in communication. This
      is by no means surprising, as the art of communication and its fundamental
      significance for the physicians and their work have still not found entry into
      medical curricula. As long as physicians define their very old patients
      exclusively in terms of their increasing physical weaknesses, their task can only
      be restricted to improving patients' weakened condition to a very limited extent.
      The patient well advanced in years is thus not recognized as an individual person
      with feelings, worries and desire desire to find a meaning in life.

PMID- 15490764
TI  - [How dangerous are patients with mental disorders?].
AB  - The question of potential violence on the part of people with a mental disease
      has caused considerable controversy in recent decades. While in the eighties the
      prevailing opinion was that they have no increased risk of aggression, recent
      studies, especially from Scandinavia and Canada, show a moderate but reliable
      coherence between violent crime and paranoid and schizophrenic diseases. The
      danger of people with a mental disease is assessed essentially through the
      following five study-approaches: Studies to assess the criminal rate of
      hospitalised patients, the prevalence of mental disorder, studies on prisoners
      who are committed to a psychiatric facility, and long-term analyses of cohorts.
      Special emphasis is attached to investigations on homicides. Other investigative
      questions are concerned with the influence of psychopathological symptoms, the
      importance of comorbid disturbances and sociological aspects. The studies agree
      that the risk of violence is decisively increased in people who suffer from
      schizophrenia, through additional substance abuse, comorbidity with personality
      disorders, absence of treatment and social desintegration. An unprejudiced
      approach to this sensitive theme of aggression in people with schizophrenia with
      regard to further effective prevention and therapy is required.

PMID- 15490765
TI  - [Sexuality--psychosomatic representation of the relationship].
AB  - A salutogenic understanding of sexuality as a means of non-verbal communication
      embodiing essential basic needs, e.g. for acceptance, closeness, warmth,
      security, as they are sought in all relationships, is explicated from the point
      of view of sex therapy. Hence, a relation-oriented or syndyastic sex therapy
      focuses on the fulfillment of these basic needs and desires in general as well as
      by sexual commmunication in particular and thus creates favourable conditions for
      relieving sexual dysfunctions. Couples learn to relate sexuality with basic needs
      and connect it to lust, thus enhancing quality of life as well as psychosomatic
      well-being and health.

PMID- 15490766
TI  - [Forms of pathological gambling: empirical research on consumers behaviour of
      sport betting and lottery participants].
AB  - Gambling is one of the favourite leisure activities. 70-90 % of the grown-up
      population have gambled at least once in their life. Over the last few years,
      however, the variety of opportunities to gamble has changed. Decreasing numbers
      of casino visitors can be seen against an ever-increasing number of people using
      slot machines, and taking part in national lotteries and sport betting.
      Comprehensive empirical research regarding consumer behaviour and addiction
      potential involved in sport betting has been non-existent and only a few studies
      have dealt with lottery. In the present study, 108 subjects were questioned in
      Austrian betting offices. 33.3 % of the sample fulfilled the diagnostic criteria
      for pathological sport betting. Of the sport betting subjects who additionally
      play lottery, 22.92 % were diagnosed as being pathological lottery gamblers.
      Based on the criteria of substance addiction, the data demonstrate that sport
      betting and lottery have addiction potential and can therefore be seen as non
      substance-related addiction.

PMID- 15490767
TI  - [Inpatient treatment of woman with depressive disorders due to stress--does
      inclusion of the partner in treatment influence outcome? A randomized,
      controlled, prospective study].
AB  - BACKGROUND: The incorporation of couple therapy into the treatment concepts of
      inpatient psychotherapy has been intensified in recent years. However, no
      controlled studies on its efficacy have as yet been undertaken. The aim of this
      study was to examine this question in the case of women with depressive
      symptomology related to overstress. METHODS: In a prospective, randomized and
      controlled study, the monitored results of 31 female inpatients (15 for whom the
      partner was incorporated into the therapy and 16 without additional partner
      therapy) were compared with each other (response rate 91.2 %). The period of
      observation amounted to six weeks. The Beck Depression Inventory (BDI) and the
      Questionnaire on Changes in Experience and Behavior) (VEV) were employed as
      instruments of assessment. RESULTS: VEV assessment after six weeks resulted in a
      significant difference between patients who received regular sessions in couple
      therapy in an inpatient treatment setting and those who were treated without
      inclusion of the partner (p < 0.01). The Beck Depression Inventory likewise
      yielded a statistically significant difference between the results for both
      groups (p < 0.05). CONCLUSIONS: There are indications that female patients with
      depressive symptomology related to overstress, who are treated in an inpatient
      setting with additional, consistent couple therapy, achieve significantly better
      treatment results than those who are treated without the inclusion of their
      partners.

PMID- 15490768
TI  - [Acamprosate--new preclinical research aspects].
AB  - Acamprosate has been shown to be effective and safe in relapse prevention of
      alcoholism. The effect of acamprosate is explained by a functional antagonistic
      action on the N-methyl-D-aspartate (NMDA) receptor. Under normal physiological
      conditions acamprosate augments the functionality of the NDMA receptor, but it
      inhibits the overactivity of that receptor triggered by alcohol abuse and
      withdrawal. In addition, conditioned withdrawal phenomena that can lead to a
      relapse, are also reduced. The substance is not a substitution drug, nor does it
      have addictive potential. Moreover, it also has a neuroprotective action. Whether
      acamprosate has a role as a neuroprotective agent in humans needs to be
      investigated.

PMID- 15490769
TI  - [Advances in the treatment of alcohol dependence: pharmacological relapse
      prevention].
AB  - The development and successful clinical examination of relapse preventing
      medications (so-called anti-craving substances) opens up completely new
      perspectives in the treatment of alcohol-dependent patients. This is especially
      important for the general practitioners since despite of improved psychosocial
      treatment of alcohol-dependent patients relapse rates after detoxification remain
      high. Since a few years, new medications reducing the relapse risk are available.
      In Germany acamprosate presently is the most important medication used for this
      indication. Compared with placebo treatment, approximatly twice as many patients
      remain abstinent under acamprosate one year after detoxification. The
      administration of the medication starts immediately after detoxification and
      supports the patient during the first months, when the relapse risk is especially
      high. The medical treatment, however, is not a replacement for a psychosocial
      treatment of the alcohol dependence, but should be accompanied by counselling and
      the attendance in self help groups.

PMID- 15490770
TI  - [Controlled-release oxycodone--a therapeutic option for severe neuropathic pain.
      Two multicenter observational studies].
AB  - Two postmarketing studies (PMS) involving 603 patients with neuropathic pain
      treated with controlled-release oxycodone were performed. Pain intensity and
      impairment of performance were evaluated using a numeric rating scale (NRS)
      ranging from 0 to 10 (0 = no pain/impairment, 10 = most severe pain/impairment)
      measured at the start of the study, and at one week and some three weeks into the
      study. Mean pain intensity decreased from more than 6 at the start of the PMS to
      about 4 after one week, and under 3 after three weeks, of treatment. The mean
      dose of oxycodone after three weeks was slightly more than 40 mg per day.
      Impairment, quality of life and performance (daily activities, mood, sleep
      quality and joie de vivre) improved substantially.

PMID- 15490771
TI  - [Blood pressure lowering by the ACE-inhibitor spirapril. "24-hour efficacy of
      real once daily application of spirapril (HERAS study)"].
AB  - AIM, PATIENTS AND METHODS: In this open multicentre study, the effect of the ACE
      inhibitor spirapril on office blood pressure and 24-hour blood pressure
      regulation was investigated. A total of 845 general practices recruited 2,491
      patients to the 12-week study. Included were patients with newly diagnosed
      hypertension receiving spirapril alone, and patients who had already been taking
      antihypertensive agents and who were changed over to monotherapy with spirapril.
      Also included was a group of patients receiving spirapril in addition to other
      antihypertensives. Data were collected separately both from the group as a whole
      and also from a subgroup of patients receiving spirapril (6 mg/day) for whom 24
      hour blood pressure records were available at the start and termination of the
      study (n=606). RESULTS: The 24-hour blood pressure measurements showed a decrease
      of the mean diurnal systolic blood pressure from 150.9 mmHg to 134.7 mmHg, and of
      the mean nocturnal blood pressure from 138.1 mmHg to 123.2 mmHg. The
      corresponding mean diurnal diastolic blood pressure decreased from 88.8 mmHgto
      81.4 mmHg, and the mean nocturnal pressure from 79.6 mmHg to 72.2 mmHg. The
      toterability of spirapril proved to be very good with a side effect rate of 1.3
      %. No serious adverse reactions were observed. CONCLUSION: The results show that
      in general practice use spirapril effectively lowers blood pressure, and is very
      well tolerated. The blood pressure decrease is maintained over the entire 24
      hours and is still clearly evident towards the end of the period, that is, in the
      critical early morning hours.

PMID- 15490772
TI  - [IRMA-pRAcs: irbesartan in the treatment of microalbuminuria and proteinuria in
      patients with type 2 diabetes and hypertension-prospective observational study
      involving 38,016 patients in the general practice setting].
AB  - BACKGROUND AND AIMS: In daily practice, nephropathy is diagnosed in a high
      percentage of type 2 diabetics, including those in whom blood pressure is well
      controlled. The aim of the present study was to reduce albuminuria in these
      patients by changing over antihypertensive treatment to the AT, blocker
      irbesartan. 9,838 general practitioners recruited a total of 38,016 type 2
      diabetics aged at least 18 years to an open observational study: In the majority
      of cases, current antihyprertensive treatment was discontinued and patients given
      300 mg (a small percentage received 150 mg or 75 mg) irbesartan, either as
      monotherapy or in combination with 12.5 mg hydrochlorothiazide (HCT). The primary
      target outcome for efficacy was the 6-months normalization rate in patients with
      microalbuminuria or proteinuria; secondary target parameters included the change
      in protein excretion (grades: negative, 20 mg, 50 mg, 100 mg), normalisation of
      the systolic or diastolic blood pressure, and responder and blood pressure
      normalization rates. The target criterion for tolerability was the number of
      patients with adverse events (AE). RESULTS: 46% of the patients were controlled
      with 300 mg irbesartan alone, and 40% with irbesartan in combination with HCT.
      Albumin excretion normalized in 60.5% of the patients, improved by at least one
      grade in 81.9%, remained unchanged in 17.5%, and increased in 0.7% of the cases.
      The beneficial response was found to be independent ofthe type of prior
      antihypertensive treatment (including ACE-inhibitors) and was also seen in
      normotensive patients. Only 0.4 % of the patients reported AEs. CONCLUSION: In
      type 2 diabetics, treatment with 300 mg irbesartan administered alone or in
      combination with 12.5 mg HCT produced a pronounced nephroprotective effect.

PMID- 15490773
TI  - [Treatment of behavioral disorders in dementia with risperidone in
      psychogeriatric out-patients].
AB  - BACKGROUND: The atypical neuroleptic drug risperidone has been approved for the
      treatment of behavioural and psychological symptoms of dementia for more than
      three years in Germany. To assess the efficacy and tolerability of risperidone in
      general practice two open-label prospective studies were performed. PATIENTS AND
      METHOD: In 7142 patients with dementia the treatment course with risperidone was
      examined over 6 resp. 8 weeks. Efficacy was evaluated by assessing the target
      symptoms agitation, aggression, sleep-wake-cycle disturbances, social withdrawal,
      suspiciousness, and delusion. Furthermore, the global impression was rated by the
      physician and the caregiver at the end of the study. The tolerability of
      risperidone was documented by monitoring blood pressure, heart rate, bodyweight,
      and adverse events. RESULTS: 6170 patients complied with the inclusion criteria
      for analysis. Risperidone achieved statistically significant improvements of
      behavioural symptoms at an average dose of 1,5 mg/d (90% of patients received <
      or = 2 mg/d). 92% of the patients showed a favourable treatment response as
      defined by a > or = 30% improvement of the total score of the target symptoms.
      This improvement was already apparent 2 and 3 weeks after the start of treatment,
      respectively. A subgroup analysis demonstrated statistically significant
      improvements of target symptoms with risperidone also in patients who had been
      pre-treated with other neuroleptics. The global impression of physician and
      caregiver was positive in over 90% of patients. Adverse events were seen in 309
      of 6170 patients (5,7%). CONCLUSION: Risperidone was highly effective and well
      tolerated in the treatment of behavioural disturbances in dementia under routine
      conditions of general practice.

PMID- 15490774
TI  - [Consensus of the German and Austrian societies for wound healing and wound
      management on vacuum closure and the VAC treatment unit].
AB  - Within the framework of the Three-Country Congress on VAC Treatment (Vacuum
      Assisted Closure Treatment) held on May 16/17 2003 in Salzburg, a Consensus
      Conference involving members of the Committees of the German and Austrian
      Societies for Wound Management was convened. In view of the divergence of opinion
      on the effectiveness of the treatment among the cost carriers, it appeared
      appropriate for the two Societies for Wound Healing in Germany and Austria to
      arrive at a consensus on the importance of and the indications for the management
      of wounds with the vacuum closure method. Since the first clinical applications
      in the nineteen-forties, both the indication spectrum and the number of
      applications have increased continually. In addition to diverse vacuum closure
      systems, there is patented computer-controlled system technology available that
      is established VAC treatment. Although this is a hospital-based system, it can
      also be used on an outpatient basis by appropriately trained physicians and
      nursing staff and in instructed patients. For some indications, vacuum closure
      and VAC management is considered the treatment of choice, since no equivalent
      alternative methods are available. A cost-benefit analysis shows that vacuum
      closure and VAC treatment is cost effective.

PMID- 15490775
TI  - Science and dentistry.

PMID- 15490776
TI  - Correlation between cervical spine and temporomandibular disorders.
AB  - Neuroanatomical interconnections and neurophysiological relationships between the
      orofacial area and the cervical spine have been documented earlier. The present
      single-blind study was aimed at screening possible correlations between clinical
      signs of temporomandibular disorders (TMD) and cervical spine disorders. Thirty
      one consecutive patients with symptoms of TMD and 30 controls underwent a
      standardised clinical examination of the masticatory system, evaluating range of
      motion of the mandible, temporomandibular joint (TMJ) function and pain of the
      TMJ and masticatory muscles. Afterwards subjects were referred for clinical
      examination of the cervical spine, evaluating segmental limitations, tender
      points upon palpation of the muscles, hyperalgesia and hypermobility. The results
      indicated that segmental limitations (especially at the C0-C3 levels) and tender
      points (especially in the m. sternocleidomastoideus and m. trapezius) are
      significantly more present in patients than in controls. Hyperalgesia was present
      only in the patient group (12-16%).

PMID- 15490777
TI  - Clinical evaluation of different adhesive systems for restoring teeth with
      erosion lesions.
AB  - This investigation evaluated the performance of a resin-modified glass ionomer, a
      compomer, and a bonding system/composite combination for the restoration of
      cervical erosion lesions without cavity preparation. Forty-eight lesions (11
      patients) were restored with a bonding agent/composite combination [Prime & Bond
      2.1/PrismaTPH (P & B/TPH); DeTrey/Dentsply], a compomer (Dyract;
      DeTrey/Dentsply), or a light-curing glass ionomer (Fuji II LC; Fuji). The
      materials were randomly assigned to the patients in triplets. No cavity
      preparation was performed. The procedures strictly followed the manufacturers'
      instructions. The restorations were evaluated clinically, using modified USPHS
      criteria, and by quantitative scanning electron microscope (SEM) analysis, at
      baseline and 12 months. The clinical data were statistically evaluated with the
      Pearson chi-square test, the SEM data (criterion gap formation) were analyzed
      with the Mann-Whitney U-test and error rates method. Clinically, two restorations
      could not be evaluated. One Dyract restoration failed. With respect to marginal
      discoloration, recurrent caries and contour, no significant differences could be
      found between the materials. The surface texture of P & B/TPH and Dyract was
      significantly better than that of Fuji II LC at baseline and 12 months. Compared
      to P & B/TPH and Fuji II LC, Dyract revealed a significant decrease in marginal
      integrity between baseline and 12 months. In SEM analysis, gap formation was
      determined as follows: baseline, enamel interface: 4% Dyract= 4% Fuji >2% P &
      B/TPH and dentin interface: 11% Dyract >9% P & B/TPH >2% Fuji; 12 months, enamel
      interface: 15% Dyract >4% Fuji >3% P & B/TPH and dentin interface: 11% P & B/TPH
      >6% Fuji >5% Dyract. The error rates method revealed no significant differences,
      in general, between the three materials with regard to gap formation. In
      conclusion, the restorations of erosion lesions with different classes of
      adhesive materials were well retained after 12 months. None of the materials
      studied revealed superiority over the other materials. All materials revealed
      shortcomings with respect to either surface texture, marginal integrity or color
      stability clinically and for all materials gap formation was recorded in the SEM
      evaluation.

PMID- 15490778
TI  - Prevalence and quality of root canal fillings in a German adult population. A
      survey of orthopantomograms taken in 1983 and 1992.
AB  - The few studies in which prevalence, technical quality, and success rates of root
      canal fillings performed in daily practice have been assessed demonstrated a high
      proportion of inappropriate root fillings and a great variety of periapical
      radiolucencies (25-60%). The aim of the present retrospective radiographic study
      was to determine if changes in prevalence, technical quality, and success of root
      canal fillings had occurred within a decade. To achieve this goal,
      orthopantomograms taken in patients who attended a University Dental Clinic for
      the first time in 1983 (group A) and in 1992 (group B) were evaluated by a
      calibrated examiner. The following criteria were applied to assess the root
      filled teeth: length and homogeneity of the root fillings and the periapical
      state. The prevalence of root-filled teeth increased significantly from an
      average 0.5 per person in 1983 to 0.8 per person in 1992. The increase was
      proportionally greater in older patients. In group A, 55.2% of the root fillings
      ended 0-2 mm before the radiographic apex and in group B this percentage was
      56.8. Insufficient homogeneity was found in 25.0% (group A) and 21.9% (group B)
      of the root fillings. The prevalence of root-filled teeth without periapical
      destructions was 76.1% (group A) and 74.1% (group B). It is concluded that, in
      the future, endodontic treatment need will increase because of the steadily
      growing number of older people. Further efforts in research and dental education
      should focus on the treatment of curved root canals.

PMID- 15490779
TI  - Treatment of injuries to the inferior alveolar nerve after endodontic procedures.
AB  - Overextension of filling material into the mandibular canal after root treatment
      in the lower jaw is a rare but serious complication. Mechanical compression,
      chemical neurotoxicity and local infection may cause irreversible nerve damage. A
      report on 11 patients with neurological complaints of the inferior alveolar nerve
      after endodontic treatment is summarised. The neurological findings are dominated
      by hypaesthesia and dysaesthesia. Half of the patients reported pain.
      Hyperaesthesia is found much more rarely. Nearly all the patients had a
      combination of one or more symptoms. Initial X-rays showed root filling material
      in the area of the mandibular canal. Nine cases were treated with apicectomy and
      decompression of the nerve; in two cases, extraction of the tooth was necessary.
      Only one patient reported persistent pain after surgery. If neurological
      complaints appear after root filling in the lower jaw, a nerve injury due to root
      filling material should be ruled out. In cases of overfilling, immediate
      apicectomy and decompression of the nerve with conservation of the tooth is often
      the treatment of choice; the tooth may be preserved and the best chance of
      avoiding permanent nerve damage is provided.

PMID- 15490780
TI  - The effect of glass ionomer cement or composite resin bases on restoration of
      cuspal stiffness of endodontically treated premolars in vitro.
AB  - The purpose of the present study was to decide whether composite resin or
      conventional glass ionomer cement should be preferred as a base material in
      endodontically treated premolars. Twelve extracted human maxillary premolars were
      mounted in a universal testing machine at a 35 degrees angle. Cuspal stiffness
      was determined by applying a load of 75 N to the buccal cusp and recording the
      displacement of the cusp using inductive displacement transducers. In the same
      teeth, different cavity preparations and restorations were performed
      sequentially. Standard MOD cavities were enlarged to allow endodontic access. In
      addition, the cusps were undermined. Half of the teeth were restored to the level
      of the previous shallow cavities using conventional glass ionomer cement (Ketac
      Fil), in the rest of the teeth dentine bonding agent (Syntac) and composite resin
      (Tetric) were used instead. Finally, composite resin fillings (Tetric) were
      placed. All restorations were removed and the experiments were repeated twice.
      For each replication, the assignment of the base materials to the experimental
      groups was reversed, and ceramic inlays (Empress) were used as final restorations
      for the last replication. Improvement of cuspal stiffness achieved by
      conventional glass ionomer bases was very small, whereas composite resin bases
      increased cuspal stability by more than a factor of two. After placement of the
      final restorations, however, there was no longer a difference between teeth with
      different base materials. Nevertheless, composite resin bases might be preferred
      for two reasons. Firstly, deterioration of adhesive restorations will probably
      start at the cavosurface margins. The incidence of margin gaps, however, will not
      only compromise marginal seal but also the stabilizing effect of the restoration.
      In this situation, the resin base may still stabilize the tooth. Moreover, resin
      bases may reduce the risk of cusp fracture during the time between cavity
      preparation and the insertion of adhesive inlays.

PMID- 15490781
TI  - The efficacy of a single pocket irrigation on subgingival microbial vitality.
AB  - The object of this study was to monitor the proportion of vital bacteria
      (microbial vitality: VF in %) present in subgingival dental plaque following one
      single subgingival irrigation with saline (S), chlorhexidine (CHX) or povidone
      iodine (I2), but without any subgingival instrumentation. Its effect on the main
      composition of the microflora was also assessed. Seventeen patients with adult
      periodontitis took part in this investigation. In each patient four initially
      untreated pockets (pocket depth 5-11 mm) associated with bleeding were selected
      for the standardised pocket irrigation and plaque sampling at baseline (0 h) and
      after the following 1 h, 24 h, 7 days and 31 days. The subgingival irrigation was
      only performed once (0 h). One pocket per quadrant was irrigated using 0.9%
      prereduced S, 0.2% CHX or 0.05% I2 (Iso-Betadine Buccale). The remaining
      untreated pocket without any irrigation served as an additional control (C).
      Using an acrylic splint as a guide, paperpoints were inserted into the pocket
      precisely at the same site to collect subgingival plaque. The bleeding on
      sampling (BOS) was thereafter noted. The proportions of bacterial morphotypes
      were examined by darkfield microscopy. VF was evaluated using a vital
      fluorescence staining. The undisturbed subgingival dental plaque was composed of
      86% (median value) vital bacteria. The sampling procedure alone and the saline
      irrigation led to a decrease in the number of spirochetes but had no influence on
      the vitality of the flora. Large variations in VF could be observed in the short
      term (1 h, 24 h) irrigation effect of CHX and I2. The reduction of VF was still
      significant after 7 days (VF(CHX) 30-80%, VF(I2) 35-80%) but persisted up to 31
      days only after I2 irrigation (VF(I2) 12-90%). The findings indicated that all
      single subgingival irrigations resulted in a temporary change of the subgingival
      microflora while povidone iodine produced the longest lasting antimicrobial
      effect. Any clinical advantage of this situation should be further investigated.

PMID- 15490782
TI  - Effect of air polishing on the fluoride release of (resin-modified) glass ionomer
      cements and of a polyacid-modified composite resin.
AB  - Eight different conventional and resin-modified glass ionomers as well as a
      polyacid-modified composite were air polished and their fluoride release was
      determined in comparison to untreated controls. The air polishing was done with
      two different devices at medium and maximum setting for powder and water. Ninety
      discs of 1.5 mm thickness and 7.0 mm diameter were produced from each cement.
      These discs were stored in 5 ml deionized water at 37 degrees C. After 1 day and
      1, 4, 8, 12, and 16 weeks, the specimens were transferred into new vials with
      fresh deionized water. From the 4th week onward, the specimens (except for the
      untreated controls) were air polished on half of their upper and lower surfaces
      for 2 s each before being put into a new vial. After 20 weeks the fluoride
      released during the previous 4 weeks was determined with a fluoride ion-sensitive
      electrode. With the exception of Ketac-Cem, all cements released significantly
      more fluoride ions after air polishing, irrespective of the devices' settings.
      The differences in the amount of fluoride released among the investigated
      materials were greater than the changes in fluoride release patterns caused by
      air polishing. Air polishing increased the fluoride release by 20-60% in most of
      the materials investigated.

PMID- 15490783
TI  - Onset, development and arrest of dental caries in Brazilian pre-school children.
AB  - The aim of this study was to describe the onset, development and arrest of dental
      caries in Brazilian 1- to 5-year-old children with limited access to dental care.
      The sample represented 40% of all children in these age groups attending public
      nursery school in the Federal District of Brazil. A total of 1465 children who
      benefited from fluoridated water soon after birth were examined for caries. For
      all teeth and tooth surfaces, the examination recorded whether they were sound,
      showing active or arrested lesions (non-cavitated or cavitated), filled or
      indicated for extraction. The onset of dental caries was identified at an early
      age; 89% of children were free of caries at the age of 1 year, decreasing to 28%
      at the age of 5 years. Non-cavitated lesions (active and arrested) accounted for
      71% (<2 years), 58% (3 years), 47% (4 years) and 40% (5 years) of the total
      number of surfaces showing caries experience. The corresponding values for
      cavities were 28%, 38%, 47% and 47%, respectively. Maxillary incisors and molars
      disclosed the highest caries experience in all ages. For children older than 1
      year, both mean deft and defs scores not including non-cavitated lesions were
      significantly different from those for which non-cavitated lesions were taken
      into account (t-test, P < 0.0001). At the age of 5 years, defs scores were 5.5
      and 8.8, respectively. This study documented that the onset and development of
      dental disease started at an early age in the population studied, leading to a
      considerable need for dental care.

PMID- 15490784
TI  - Cancer control in Africa: a call for action.
AB  - Cancer is an emerging public health problem in Africa especially with increasing
      frequency of HIV-associated malignancies and exposure to environmental
      carcinogens. This review attempts to highlight steps that can be taken to achieve
      effective control programmes in low-resource areas of Africa. The author reviews
      the areas of importance in cancer control programmes based on local experience.
      To implement cancer control programmes, steps must be taken to improve the data
      collection on incidence and trends of common cancers with the establishment of
      local cancer registries. There is the necessity to increase the level of
      awareness of the population about common cancers, to dispel the cultural taboos
      and myths, and teach basic preventive health measures. These can be achieved by
      well-organized sustained educational programmes extended to the grass-roots with
      community participation. The training of personnel at community level to
      recognize the early signs and symptoms coupled with provision of primary health
      care facilities and basic sustained well-planned referral system will be
      necessary to accommodate the fall-out of educational programmes and anti-cancer
      campaign. The integration of cancer control activities into the existing health
      care structure would make it easier to sustain these programmes. The cost
      effectiveness of prevention and early diagnosis of cancer cannot be over
      emphasized in Africa. With government investment in national health and provision
      of facilities for early diagnosis and treatment, effective cancer control can be
      achieved.

PMID- 15490785
TI  - The effect of histamine iontophoresis on the heart rate and blood pressure of
      female subjects.
AB  - The main purpose of this study was to determine the effect of histamine
      iontophoresis on the Blood Pressure (BP), and heart rate (HR) of female subjects.
      Twenty apparently healthy female undergraduates of Obafemi Awolowo University,
      Ile-Ife (average age 24.2 +/- 2.9) participated in the study. An automated
      electronic sphygmo-manometer that monitors both BP and HR was used to measure the
      Systolic Blood Pressure(SBP) and diastolic Blood Pressure (DBP) over the left
      brachial artery. The histamine gel used in this study contained 1 percent
      histamine dihydro-chloride. The gel was applied to the right biceps brachii and
      active was applied below the cubital fossa. The current intensity Interrupted
      Direct Current (IDC) was gradually increased and subjects were instructed to
      indicate immediately they experienced tingling sensation under the electrode. The
      same procedure was carried out the second time on the subjects with the same
      intensity of IDC current but without histamine for each subject. The treatments
      were administered on different days but within a two-week interval. The
      cardiovascular response was monitored five minutes before the administration,
      twenty minutes during the administration and five minutes after the termination
      of each treatment. Blood Pressure and heart rate did not change significantly
      from the baseline during the histamine iontophoresis and direct currents
      treatments (P > 0.05). The findings suggest that the subjects' BP and HR were not
      affected by histamine iontophoresis during the twenty minutes treatment. It was
      concluded that local administration of 1 percent histamine dihydrochloride into
      the subcutaneous tissue of females' right upper arm with the aid of direct
      current did not appreciably affect the blood pressure and heart rate after 20
      minutes of treatment.

PMID- 15490786
TI  - Prolongation of electrocardiographic intervals in women on Norplant
      contraceptive: what dangers?
AB  - This study used electrocardiography to determine any inherent cardiovascular
      dangers with the use of Norplant, an implant contraceptive among Nigerian females
      using the device. As part of a major study of metabolic, physical and
      cardiovascular changes consequent upon the use of Norplant implant contraceptive,
      all subjects underwent serial electrocardiograms at pre-insertion, 3, 6, and 12
      months of use. Given the observed prolongation ofelectrocardiographic intervals,
      the ECG of all the study subjects were secondarily analysed for QT and corrected
      QT (QTc) dispersions. QT intervals was measured from the ECG of each of the 21
      subjects who were available at pre-insertion and 12 months post-insertion; from
      the onset of QRS to the end of T wave or nadir of the curve between T and U waves
      as the case may be. Corrected QT intervals was calculated by determining the RR
      interval and using the Bazett's formula. The difference of the lowest and highest
      QT intervals and QTc intervals over the 12 leads determined their respective
      dispersions. These were then analysed. The subjects whose ages ranged from 25-45
      years weighed between 43 and 87.2 kg. The mean QT dispersion increased with time
      but did not reach statistical significance by the twelve month visit (ANOVA - QT
      dispersion 0 month vs 12 months: F=0.98, p=0.48). However the mean QTc dispersion
      increased and reached statistical significance by 12 months (0 month vs 12
      months: F=5.49, p=0.006). QT and QTc dispersion increases are known to predict
      cardiovascular death in health and disease. With the use of this device, these
      indices rose gradually with time reaching statistical significance by 12 months
      only with the QTc dispersion. The use of this device may increase the tendency to
      cardiovascular morbidity and mortality. Whether this translates into real risk
      will require a long-term study to determine. For now, application of the device
      on patients with cardiovascular disease or tendency thereof should still attract
      caution.

PMID- 15490787
TI  - Malaria diagnosis: false negative parasight-F tests in falciparum malaria
      patients in Nigeria.
AB  - This study was designed to assess the relative reliability of microscopy, the
      dipstick technique based on the detection of Plasmodium falciparum-specific
      histidine rich protein II (HRPII) (Parasight-F) and PCR assays in diagnosing
      falciparum malaria infections in Nigerian children. The prevalence of P.
      falciparum infections in enrolled patients was 100% by microscopy. Parasite
      density ranged from 329 to 81,194 parasites/microL of blood, with a geometric
      mean parasite density of 5168 parasites/microL of blood. The sensitivity of the
      HRPII based dipstick, PCR and microscopy were 80%, 92% and 100% respectively. A
      false negative rate of 20% was observed with Parasight-F as compared with
      microscopy. The parasitemia in patients with false negative Parasight-F tests
      ranged from 319 to 54,680 parasites/microL of blood. Detailed PCR analysis of
      Isolates obtained from five out of the eight patients who exhibited a negative
      Parasight-F test, showed that the average numbers of P. falciparum clones in
      these five isolates were: 1.7 +/- 1.02 with MSPI, 3.2 +/- 1.3 with MSP2 and 1.4
      +/- 1.72 with GLURP. Comparison of microscopy and HRPII results showed a
      significant (p=0.009) difference as opposed to microscopy and PCR (p=0.239). This
      study showed that caution should be exercised when excluding P. falciparum
      infections on the basis of HRPII based dipstick results alone. Microscopy or PCR
      diagnosis where possible, should be carried out in order to confirm negative P.
      falciparum HRPII-based dipstick tests.

PMID- 15490788
TI  - Prevalence of microalbuminuria in newly diagnosed type 2 diabetic patients in Jos
      Nigeria.
AB  - Diabetic nephropathy contributes significantly to end-stage renal disease in
      Nigeria. The earliest clinically detectable stage is that of microalbuminuria
      when interventions could halt or retard the progression to end-stage renal
      disease. To investigate the prevalence of microalbuminuria in newly diagnosed
      type 2 diabetic patients and its clinical correlates in Jos, consecutive patients
      with newly diagnosed type 2 diabetes attending two large hospitals in Jos were
      evaluated at three different occasions of monthly intervals for microalbuminuria
      using Micral test strips 11. Patients with proteinuria, positive nitrite test/
      urine microbial culture, acute illnesses or cardiac decompensation were excluded.
      Out of a total of 99 patients recruited, only 65 completed the study.
      Microalbuminuria was present in 32(49.2%) of the patients, and was significantly
      associated with mean arterial pressure, systemic hypertension and diabetic
      retinopathy (P < 0.05). Microalbuminuria is common in newly diagnosed patients
      with type 2 diabetes mellitus. Our finding supports routine screening for
      microalbuminuria as part of the initial evaluation of these patients.

PMID- 15490789
TI  - Wound healing activities of methanolic extracts Ocimum gratissimum leaf in Wistar
      rats - a preliminary study.
AB  - The wound healing effect of leaf extracts of Ocimum gratissimum was investigated
      in adult male Wistar rats. Two groups of adult male Wistar rats, average body
      weight 170g, had a 2cm by 2cm square wound inflicted on the dorsolateral aspect
      of their trunk with Paniculus Carnosus removed. Experimental group had their
      wound dressed with methanolic leaf extracts of Ocimum gratissimum while control
      group had their wounds dressed with normal saline dressing. All animals had wound
      dressing done every five days; wound dimension measured and, wound morphometry
      assessed. Wound biopsy was done by random selection in each group on day 10 and
      the day of complete re-epithelisation. Routine paraffin wax processing was done,
      slides stained with haematoxylene and eosin for histological assessment of
      fibroblast count, neovascularisation and granulation tissue profile. The result
      revealed significant wound contraction (P<0.05) on day 10 in the experimental
      group (mean 73.40 +/- 3.30)cm2 compared with the control group (mean 53.50 +/-
      4.32)cm2. Histology of the healed scar showed non-significant (P>0.05) decrease
      in the mean fibroblast count forthe experimental group (83.80 +/- 5.70) relative
      to fibroblast count of 90.20 +/- 17.90 in the control group. The mean blood
      vessel count was also non-significantly lowered (P>0.05) in the experimental
      group (9.20 +/- 1.20) relative to the control group (13.40 +/- 2.40). Granulation
      tissue histology on day 10 showed denser inflammatory infiltrate as reflected by
      increased cellularity in the control group relative to that of the experimental
      group which though appeared adequate was not as dense as the control group. Thus
      we suggest that the methanolic extracts of O. gratissimum could be a potential
      wound healing agent due to its ability to enhance wound contraction.

PMID- 15490790
TI  - The pattern of malignant tumours of the liver in a tertiary health institution in
      Nigeria.
AB  - This study aims at establishing the histopathological pattern of liver cancers
      reported in the Department of Pathology, University of Ilorin Teaching Hospital
      between January 1979 and December 1996. Histopathological slides and duplicate
      copies of reports were retrieved and re-examined while fresh sections were
      processed from original paraffin blocks when necessary. Liver cancers constituted
      56.6% of all liver biopsies. Hepatocellular carcinoma, which was commonest in the
      fifth decade, occurred in 64.1%, while metastatic tumours, which were commonest
      in the sixth decade, accounted for 24.7%. Primary sites could only be determined
      in 5 out of the 35 metastatic tumours. The age range of patients with Burkitt's
      lymphoma was 6-17 years with an average of 10.8 years and a male/female ratio of
      3:2. Overall, there was preponderance of hepatocellular carcinoma in males while
      metastatic tumours were commoner in females. The pattern of Burkitt's lymphoma
      demonstrated in this study agrees with what generally obtains for endemic
      Burkitt's lymphoma in this environment.

PMID- 15490791
TI  - Endemicity of onchocerciasis in some local government areas of Niger state.
AB  - The established method of justifying the need for ivermectin delivery to a
      community is the use of Rapid Assessment Method (RAM). This method involves the
      clinical examination of 50 adult males, who have been resident in the community
      for at least five years, for onchocercal nodules and leopard skin. The values
      obtained for these indices will guide the classification of such a community as
      being hypoendemic, mesoendemic or hyperendemic. Those that fall within
      mesoendemic and hyperendemic category onchocerciasis qualify for ivermectin
      delivery. This study was carried out to determine the endemicity level of
      onchocerciasis in 74 communities of 8 Local Government Areas (LGAs) of Niger
      state to justify their inclusion or otherwise in the ongoing state wide mass
      treatment for onchocerciasis using ivermectin. The communities were selected
      using the Geographical Information System (GIS) data and following the World
      Health Organization (WHO) guideline for RAM. A total of 3000 subjects were
      examined comprising of 2395 (79.8%) males and 605 (20.2%) females. None of the
      LGAs, based on overall prevalence for nodules qualify for mass treatment with
      ivermectin. However the study identified communities within some of these LGAs
      that were mesoendemic for onchocerciasis and thus qualified for mass treatment
      with ivermectin.

PMID- 15490792
TI  - Trends of ear syringing at Ibadan, Nigeria.
AB  - Ear syringing is a procedure by which the external auditory canal is irrigated
      with a normal saline at body temperature. It is a procedure which every doctor or
      nurse should be able to perform proficiently. A study of 622 patients that needed
      ear syringing was done between December 1999 and June 2001 to determine its
      trend. There were 341(55%) males and 281(45%) females with age ranged from
      3.5months to 89 years: 44.4% were in the first decade of life. Cerumen auris 99%
      remained the commonest indication for syringing in this study with bilateral
      cerumen auris constituting 53.1% while right and left cerumen auris constituted
      24.4% and 21.5% respectively. Cerumen auris constituted 66% of total 933 Otologic
      cases seen during the study period. Other indications were otitis externa 0.7%
      (otomycosis 0.5%; bacterial 0.2%) and foreign body 0.3%. The majority of patients
      (86%) required between 500mls and 1000mls of fluid for irrigation and 94.9%
      required not more than one attempt at syringing. The complications recorded were
      mainly vertigo 0.2% and tympanic membrane perforation 0.2% respectively. Thus ear
      syringing, though simple and sometimes taken for granted may be fraught with
      dangers; it is a very safe procedure in trained hands and that after at least
      three attempts of ear syringing for cerumen auris and if it persists despite
      effective applications of cerumenolytic agents prior to irrigation, the procedure
      should be discontinued and other methods of imparted cerumen auris removal should
      be employed.

PMID- 15490793
TI  - Psychosocial and seizure factors related to depression and neurotic-disorders
      among patients with chronic epilepsy in Nigeria.
AB  - To establish the effect of psychosocial and seizure factors on Depression and
      Neurotic Disorders among clinically diagnosed Nigerian patients, with epilepsy.
      This study utilized the multivariate statistical design to evaluate the
      associations between some psychosocial and seizure factors on increase depression
      and neurotic disorders. The Neurology outpatient clinics of two tertiary
      facilities in Nigeria: Aro Neuro-psychiatric Hospital/World Health Organization
      Collaborating Centre, Abeokuta and the University College Hospital Ibadan, were
      used for the study. Two hundred and sixty four (264) consecutive clinic attendees
      with a clinical diagnosis of epilepsy participated in the study. Perceived Stigma
      Scale (PSS); Washington Psychosocial Seizure Inventory (WPSI-Modified): Becks
      Depression Inventory (BDI) and Crown-Crisp Experiential Index (CCEI). Significant
      main effect for seizure control, stigma, emotional adjustment, vocational
      adjustment, interpersonal adjustment, adjustment to seizures but not for age at
      onset of epilepsy, financial adjustment and gender, were recorded on depression.
      Similarly significant main effect for seizure control, stigma, emotional
      adjustment, adjustment to seizures but not for age at onset of epilepsy, gender,
      vocational adjustment, financial adjustment and interpersonal adjustment were
      recorded for neurotic disorders. The study highlights some of the factors, which
      may contribute to the understanding of epilepsy-related psychopathologies and
      implication for psychotherapeutic intervention among individuals with epilepsy in
      Nigeria.

PMID- 15490794
TI  - HIV: knowledge and sexual practices amongst students of a school of communnity
      health in Lagos, Nigeria.
AB  - A cross sectional study was conducted amongst students of a school of health
      technology in Yaba. Lagos. Nigeria to determine their knowledge about HIV/AIDS
      and their sexual practices. A self-administered questionnaire was used to collect
      data. Two hundred and thirty-six students out of 250 participated in the study
      (94% response rate). The mean age was 24.7+5.2 years, 167 (71%) respondents were
      females while 69 (29%) were males. One hundred and seventy-seven (75%) students
      were single and 59 (25%) were married. Knowledge on HIV was graded using twenty
      nine items on the questionnaire, each scored one mark. A maximum score of 29 was
      obtainable and respondents with scores greater than 50% were classified as having
      a satisfactory level of knowledge. Ninety-nine percent had heard about HIV/AIDS
      through several sources. Knowledge of symptoms, methods of transmission and
      prevention were generally satisfactory. One hundred and seventy one (72%)
      students were sexually active, 48% engaged in casual sex and 9% had multiple
      partners. Of the 171 who were in sexual relationship with a primary partner, 49
      (29%) used condoms all the time. One hundred and fourteen (48%) admitted to
      having casual sex but 60 (53%) used condoms all the time during casual sex.
      Partner and personal dislike as well as reduction in sexual pleasure were reasons
      for non-use of condoms. A significantly higher proportion of students in the
      higher classes (74/94, 79%) possessed a higher level of knowledge than those in
      the lower class (78/142, 55%, p=0.0003). One hundred and fifty-two (64%) students
      possessed a satisfactory level of knowledge on the subject, but many engaged in
      risky behaviour.

PMID- 15490795
TI  - Substrate profile variation and drug resistance patterns of a - lactamase
      producing Shigella species isolated from diarrhoeal patients in Lagos, Nigeria.
AB  - The number and trend of antibiotic resistance by Shigella species recovered from
      food and diarrhoeal stools are on the increase in Nigeria and has resulted in a
      high frequency of hospitalisation. Increased cost of disease management, and
      higher mortality in children. This study exposes 51 a-lactamase producing
      Shigella isolates from Lagos to some newly introduced drugs in the country. The
      drugs include a-lactam - a-actamase inhibitor antibiotics. a-lctam substrate
      hydrolysis and inhibitory effects of clavulanate were also investigated in-vitro.
      Results obtained revealed that all the isolates showed high level resistance to
      tetracycline, ampicillin, streptomycin, co-trimoxazole and amoxicillin with an
      MIC range of 128 - 1024 microg/ml. The isolates were susceptible to piperacillin,
      tobramycin, aztreonam and ofloxacin (0.03 - 8 microg/ ml). 18.2 - 40.9% of S.
      flexneri and S. dysenteriae showed low level resistance to cefuroxime and
      cefotaxime (MIC = 4 - 16 microg/ ml). Among the a-lactam - a- lctamase inhibitors
      tested, only piperacillin-tazobactam showed 100% resistance. Hydrolysis of a 
      lctam substrate was found to be species dependent in decreasing order of S.
      flexneri, S. dysenteriae, S. sonnei and S.boydii. An IC50 range of 0.8-2.4 mM was
      also observed in these isolates. Our data indicate that the incidence of
      multidrug resistance is high among a-lactamase producing Shigella isolates in
      Lagos, Nigeria. While the third generation cephalosporins should be used with
      cautions, some of the newly introduced drugs have the prospects of being used in
      the future control and management of shigellosis in the country.

PMID- 15490796
TI  - Clinical manifestations and immune response to MSP 1(19) in severe paediatric
      malaria in Adeoyo state maternity hospital, Ibadan.
AB  - A 10-week cross-sectional study was carried out at the Adeoyo State Maternity
      Hospital (Beere, Ibadan), Southwestern Nigeria in order to determine (a) the
      prevalence of severe malaria, (b) identify the predominant clinical presentations
      that characterise the disease in children below 5 years and the pattern of
      antibody responses to MSP 19 elicited in severe malaria complications. Three
      thousand, one hundred and thirty-one cases reported to the Out Patients'
      Department; of these, 372 (11.8%) subjects were recruited on the basis of
      doctors' diagnosis of severe malaria, malaria and other complications. Six per
      cent (188/3131) ofthe patients were admitted. Serum samples for 320 ofthe 372
      subjects were analysed for antibodies specific to MSP 1(19) by ELISA. The highest
      antibody responses occurred in the age group 2-5 years. Parasite prevalence was
      77.9% (290 of 372 subjects) and parasite density ranged from 80 to >100000
      parasites/microL blood. Fever (an average temperature of 38.6 +/- 0.4 degrees C
      and peak at 41 degrees C) and severe malaria were the major clinical
      manifestations of malaria amongst the study population. Severe malaria was found
      to be associated with other features such as cough, vomiting and diarrhoea.

PMID- 15490797
TI  - Stomal recurrence post laryngectomy in University College Hospital, Ibadan.
AB  - The outcome of laryngeal carcinoma is favourable and cure rate high if detected
      early. A major complication experienced post surgery for advanced laryngeal
      carcinoma is recurrence especially at the tracheostome. This study aimed at
      evaluating the incidence of stomal recurrence post total laryngectomy with
      respect to the risk factors. This is a retrospective review of eighteen patients
      (14 males and 4 females) that had total laryngectomy for histologically confirmed
      laryngeal carcinoma from 1990 - 2002. Seven patients (38.9%) had stomal
      recurrence. Seven patients (38.9%) had palpable deep cervical nodes at
      presentation. Fourteen (77.8%) and four (22.2%) patients had emergency and
      elective tracheostomy procedures respectively. Twelve patients (66.67%) had neck
      node dissection during surgery. Post-operatively, twelve patients (66.7%) had
      only radical radiotherapy; four (22.2%) had both radio-/ chemotherapy while two
      had preoperative and additional postoperative radiotherapy. The mean duration
      between the preoperative tracheostomy and total laryngectomy was 62.19 +/- 64.56
      days while the mean duration between total laryngectomy and development of stomal
      recurrence was 7.79 +/- 8.57 months. Ten patients (55.6%) died, (seven with and
      three without stomal recurrence but who died of distant metastases to the lungs
      and thoracolumbar vertebral bodies). Stomal recurrence post laryngectomy has a
      grave prognosis. This present study also showed that advanced stage 3 and 4
      tumour, transglottic involvement and the presence of preoperative tracheostomy
      are the likely risk factors that could be associated with recurrence in our
      environment. There is therefore the need to reevaluate these preventive measures
      in a prospective study in order to improve the final outcome in our environment.

PMID- 15490798
TI  - Changing patterns in sensitivity of causative organisms of septicaemia in
      children: the need for quinolones.
AB  - A review of the pattern, and antibiotic sensitivities of blood culture isolates
      over a 3 year period in children presenting to the Paediatric Unit of Ahmadu
      Bello University Teaching Hospital, Kaduna is reported. Positive blood culture
      isolates were obtained in 26.9% of 1,982 children. The most prevalent isolates
      were Staphylococcus aureus (59.9%), Escherichia coli (16.9%) and Klebsiella
      (16.3%). There was a striking paucity of isolation of Salmonella typhi (1.3%) and
      Streptococcus. Sensitivity to commonly used drugs like ampicillin/cloxacillin,
      genticin, ceftazidime and chloramphenicol was low (8.0-50.0%), with a
      corresponding delayed fever resolution and prolonged hospital stay. 31.0-83.3% of
      the isolates were highly sensitive to pefloxacin, norfloxacin and ofloxacin,
      which were not generally recommended for use in paediatric patients. In two
      patients with no response to commonly used antibiotics, use of quinolones lysed
      their fever within 48 hours. This change of antibiotic sensitivity patterns calls
      for a thorough investigation into the potential role of these quinolones in
      paediatric chemotherapeutics either singly or in appropriate combinations with
      existing antibiotics.

PMID- 15490799
TI  - In vitro and in vivo antimalarial studies of Striga hermonthica and Tapinanthus
      sessilifolius extracts.
AB  - The antimalarial activities of the methanol extracts of Striga hermonthica (whole
      plant) and Tapinanthus sessilifolius (leaves), commonly used in Northern Nigeria
      for the treatment of malaria, were evaluated. In the in vitro antiplasmodial
      analysis, the extracts of T. sessilifolius and S. hermonthica utilized in the
      study, displayed mild to weak activities with IC50 values of 200.5 and 274.8
      microg/ml respectively. This was investigated, using the multidrug resistant
      Plasmodium falciparum, K1 strain, in the parasite lactate dehydrogenase assay.
      The murine model in vivo antimalarial activity of the tested extracts, using
      chloroquine-sensitive Plasmodium berghei (ANKA P1), in the 4-day suppressive
      test, showed that both plants had intrinsic antimalarial properties, that were
      dose-dependent. At a dose of 400mg/kg weight of mice, extract of S. hermonthica
      exhibited a higher intrinsic antimalarial activity (68.5 % suppression) than that
      of T. sessilifolius (51.3 %). Chloroquine, the standard reference drug, had an
      average suppression of 78.0 % at a dose of 10 mg/kg weight of mice while normal
      saline was used as control. Preliminary phytochemical screening of the extracts
      indicated the presence ofsaponins, tannins, flavonoids, volatile oils and cardiac
      glycosides.

PMID- 15490801
TI  - Hypopharyngeal paraganglioma: a case report.
AB  - Paragangliomas are neuroendocrine neoplasms that primarily afflict patients
      during the fourth and fifth decades of life. The majority of extra-adrenal
      paragangliomas arise in the head and neck region, notably from the carotid and
      aortic bodies, jugular bulb and tympanic plexus. Although one-fifth of all
      parapharyngeal neoplasms are paragangliomas, primary hypopharyngeal paraganglioma
      is relatively uncommon, only one other case having previously been documented by
      Filippin et al. (1989). We report a second case of hypopharyngeal paraganglioma
      in an 18-year-old male as seen in our center.

PMID- 15490800
TI  - Plasmodium berghei: efficacy and safety of combinations of chloroquine and
      promethazine in chloroquine resistant infections in gravid mice.
AB  - Efficacy and safety of combinations ofChloroquine (CQ) and doses of Promethazine
      (PR) against CQ resistant Plasmodium berghei infections in gravid mice was
      evaluated. Parasites were cleared faster in mice treated with CQ combined with
      doses of PR ranging from 20mg/kg to 50mg/kg (3.4 +/- 0.5 to 2.7 +/- 0.7) compared
      with CQ alone (4.7 +/- 0.8) (P<0.5). Parturition resulting in live pups in
      animals treated with CQ and 20mg/ kg and 30mg/kg of PR (81%) was significantly
      higher than in animals treated with CQ alone (44%) or saline (13%). Mean birth
      weight of pups delivered by infected gravid animals treated with CQ and 30mg/kg
      or 40mg/kg of PR (1.51 +/- 0.16 or 1.56 +/- 0.16) was significantly higher than
      animals treated with CQ alone (1.33 +/- 0.13) (P=0.00004, 0.0014 respectively).
      No gross malformations were observed in pups delivered by infected or non
      infected animals treated with the combinations of chloroquine and Promethazine.

PMID- 15490802
TI  - Cancer clinical trials, UK research networks and the shape of things to come.

PMID- 15490803
TI  - The RIB trial.

PMID- 15490804
TI  - PRIME II breast cancer trial.

PMID- 15490805
TI  - Conformal rotation therapy with central axis beam block is a feasible alternative
      to intensity-modulated radiotherapy for chordomas of the cervical spine.
AB  - AIMS: Paraspinal tumours, such as chordoma, represent a treatment challenge for
      oncologists, requiring high dose to the target volume without exceeding the
      tolerance dose of the spinal cord. Intensity-modulated radiotherapy (IMRT) is
      helpful in achieving sharp dose gradients and conformation of dose to the target
      volume. We present a simpler technique--conformal rotation therapy with a central
      axis beam block (CRT + BB), which can provide similar dose distributions.
      MATERIALS AND METHODS: A patient with a cervical chordoma developed postoperative
      recurrence and was treated with high-dose palliative radiotherapy. Treatment was
      delivered using CRT + BB, with three fixed beams and three coplanar arcs. A dose
      of 62 Gy in 31 fractions was delivered to the 100% isodose, giving a maximum
      spinal cord dose of 49.6 Gy. The patient relapsed 2 years later, and was re
      treated using the same technique to a dose of 57 Gy in 30 fractions. Estimates of
      spinal cord repair rates in primates were used to determine the tolerance dose of
      the spinal cord for re-treatment. The patient remained well for a further 25
      months before developing local recurrence, which was treated with palliative
      chemotherapy. RESULTS: Re-treatment plans using CRT + BB and IMRT were compared.
      Dose-volume histograms show equivalence of dose to the spinal cord, although the
      IMRT plan delivered a slightly higher dose to tumour and lower dose to
      surrounding soft tissues. CONCLUSION: Treatment using CRT + BB requires careful
      planning and discussion with neurosurgeons before surgery. The normal curvature
      of the cervical spine must be eliminated if possible, and the patient must be
      immobilised with the neck horizontal. If these geometric constraints can be
      satisfied, then CRT + BB can be used as a safe and effective alternative
      treatment to IMRT for tumours at this site.

PMID- 15490806
TI  - A novel technique using customised templates for the application of fractionated
      interstitial HDR brachytherapy to the tumour bed in soft-tissue sarcomas located
      in the extremities.
AB  - AIMS: Postoperative interstitial brachytherapy of limbs is challenging, because
      it is difficult to deliver a conformal dose to the tumour bed. We developed and
      assessed a new surgical fixation system for positioning guiding tubes in
      interstitial brachytherapy in order to achieve favourable geometry. MATERIALS AND
      METHODS: A 28-year-old patient was treated with postoperative interstitial
      brachytherapy boost followed by external radiotherapy after the 11th recurrence
      of a desmoid tumour in the forearm. On the basis of preoperative imaging data,
      customised resorbable templates made of polydioxanone (PDS) were cut to fit in
      the space left by the resected tumour. These were strategically positioned in the
      tumour bed during surgery. In order to hold the brachytherapy-guiding tubes
      parallel for the duration of treatment, they were passed through a series of
      holes bored into the templates. RESULTS: Fixing the guiding tubes with PDS
      templates resulted in a fixed geometry, and thus in an optimal dose distribution
      with only little additional dose optimisation needed by the brachytherapy
      treatment planning system. An optimised dose to the tumour bed, and a reduction
      of dose to critical normal tissues, is achievable with this template system for
      sarcomas located between osseous structures. CONCLUSION: The PDS templates offer
      a more rigid fixation of the guiding tubes in relation to the surrounding anatomy
      even after the operation cavity has been closed. A tailored dose distribution can
      be achieved, thus reducing possible side-effects. Additionally, because of the
      self-resorbable nature of the material, a re-operation for template removal is
      not necessary. The potential advantages of this method are being further
      investigated.

PMID- 15490807
TI  - Virtual simulation in palliative lung radiotherapy.
AB  - AIMS: To study the accuracy of tumour-volume localisation in a comparison of
      conventional and virtual simulation for palliative lung radiotherapy. To assess
      if three-dimensional tumour outlining is necessary for the virtual simulation
      process. MATERIALS AND METHODS: Ten consecutive patients with non-small cell lung
      cancer underwent target localisation for palliative lung radiotherapy using
      conventional and virtual simulation. The treatment fields were initially marked
      with a conventional simulator using fluoroscopy, plain X-ray film and available
      diagnostic imaging. Each patient then had a computed tomography (CT), and these
      simulated treatment fields were reproduced within the virtual simulation planning
      system. Two clinicians then independently defined treatment fields using virtual
      simulation alone. The virtual simulation was achieved without outlining the
      tumour in three dimensions. The coverage of an 'ideal' CT-defined planning-target
      volume (PTV) was then calculated for each of the virtually and conventionally
      simulated fields. In addition, the amount of irradiated normal lung was measured
      using dose-volume histograms (DVH). Field sizes and differences in tumour volume
      coverage were compared. RESULTS: There was significantly greater tumour volume
      coverage using virtual simulation compared with conventional simulation (P <
      0.03). This advantage was more pronounced in tumours that were larger and those
      that were closer to the patient's midline. There was no statistically significant
      difference in the volume of uninvolved lung irradiated between the two methods.
      CONCLUSION: In this small sample of patients, we have demonstrated improved
      tumour volume coverage using virtual simulation, without increasing the volume of
      uninvolved lung treated. A simple but consistent method of virtual simulation for
      this patient group is offered as an alternative to both PTV-defined CT simulation
      and fluoroscopy-based conventional simulation.

PMID- 15490808
TI  - Small-bowel displacement system for the sparing of small bowel in three
      dimensional conformal radiotherapy for cervical cancer.
AB  - AIMS: The efficacy of the small-bowel displacement system (SBDS) in three
      dimensional conformal radiotherapy (3-D CRT) planning for sparing the volume of
      small bowel is presented for cervical cancer. MATERIALS AND METHODS: Ten
      consecutive patients, who received pelvic radiation therapy for uterine cervical
      cancer with the SBDS from January to March 2003, were included in this study. The
      SBDS consists of a customised Styrofoam compression device, which can displace
      the small bowel out of the radiation fields, and an individualised immobilisation
      board. With oral contrast before scanning, computed tomography was taken in the
      prone position with and without the SBDS. 3-D conformal planning was carried out,
      and dose distribution was compared in the target volumes and in the organs-at
      risk with and without the SBDS. RESULTS: In all patients, the SBDS significantly
      reduced the small-bowel volume within radiation fields. The median small-bowel
      volume with SBDS was reduced by 56.4% compared with the small-bowel volume
      without SBDS (from 491 to 214 cm3; P = 0.004). Among the 10 patients, the highest
      small-bowel volume reduction was 70.2% (from 544 to 62 cm3). At the prescription
      dose, the median volume of small bowel irradiated was reduced significantly with
      SBDS (9.8% vs 1.2%; P = 0.005). Differences in the dose-volume histogram for the
      rectum and the bladder between the 3-D CRT plans with and without SBDS were not
      statistically significant (P > 0.1). All patients completed radiotherapy without
      a break in treatment. CONCLUSION: The SBDS is a novel method that can be used to
      displace the small bowel away from the 3-D CRT fields effectively, and reduce
      radiation therapy morbidity.

PMID- 15490809
TI  - The opinion of general practitioners on the treatment of prostate and breast
      cancer in elderly people: results of a survey based on clinical models.
AB  - AIMS: Several publications have reported age-related differences in the
      management of people with cancer. Most data have been derived retrospectively
      from hospital or cancer-centre databases. The aim of the present study was to
      identify major decisional factors observed in general practitioner (GP)
      practices, outside the hospital setting, regarding the clinical management of
      patients with prostate and breast cancer. MATERIALS AND METHODS: During three
      national GP meetings in Belgium, questionnaires presenting two simulated patient
      cases were presented to GPs who were asked two questions: one regarding further
      staging and referral of the case and the second regarding the treatment of the
      case. A total of 678 questionnaires were distributed. GPs received two randomly
      selected cases each: a breast cancer history and a prostate cancer history. Three
      variables were assessed simultaneously: age, performance status and medical
      history (comorbidity). RESULTS: The analysis indicated that elderly patients were
      more likely to be referred for non-curative treatment (OR 13.71; 95% CI 5.67
      33.12; P < 0.0001 for prostate cancer and OR 17.67; 95% CI 4.04-77.31; P < 0.0001
      for breast cancer). The other variables (performance status and medical history)
      did not affect treatment orientation. However, GPs were prepared to seek
      assistance from oncologists in both cases, irrespective of the patient's age.
      CONCLUSION: Age seems to be more important among GPs in deciding how to manage
      cancer patients than performance status and comorbidity. This is a very common
      prejudice. They are, nevertheless, inclined to refer people with cancer to
      oncologists independently of the patient's age.

PMID- 15490810
TI  - Information given to patients about adverse effects of radiotherapy: a survey of
      patients' views.
AB  - AIMS: In practice, clinicians vary markedly in the amount of information they
      give to patients before consent for investigation or treatment is obtained. We
      present a study to evaluate the amount of information patients feel that they
      should be given. MATERIALS AND METHODS: Between October 2001 and February 2002,
      82 adults were enrolled into the study before commencing treatment with
      radiotherapy. Participants were interviewed with the aid of a questionnaire, and
      responses were analysed to detect differences related to age, sex, disease site,
      treatment intent and social class. RESULTS: The distribution of responses to the
      interview was large. For a mild side-effect, 23 patients (28%) wanted to be
      informed if the risk of the side-effect was as small as 0.1%, whereas 25 patients
      (31%) would only want to be informed if there was either a 50% or a 100% chance
      of it occurring. For severe side-effects, 36 (44%) wanted to be informed of a
      0.1% risk, whereas 13 (16%) only wanted to be informed if the risk was either 50%
      or 100%. There was no association with sex, treatment intent (radical or
      palliative), social class or disease site. Information requirements tended to be
      greater in people under 60 years. This reached statistical significance (P =
      0.007) for severe side-effects, where younger patients were more likely to want
      to be informed of a side-effect if there was a 10% or less chance of it
      occurring. CONCLUSIONS: Information needs varied widely within our survey
      population. It is difficult to predict how much information patients feel they
      need before giving informed consent. Therefore, a patient-centred approach must
      involve tailoring information to individual patient requirements.

PMID- 15490812
TI  - How should we introduce clinical positron emission tomography in the UK?
      Oncologists need to have a (clearer) view.

PMID- 15490811
TI  - Giving patients a choice improves quality of life: a multi-centre, investigator
      blind, randomised, crossover study comparing letrozole with anastrozole.
AB  - AIMS: Although the third-generation aromatase inhibitors are generally well
      tolerated, side-effects still occur in up to 40% of women. As more women are
      taking these drugs for longer, the issue as to which version is better tolerated
      is now a significant patient concern. This study aimed to assess whether
      tolerance for either letrozole or anastrozole can differ for each individual in
      terms of early quality of life (QoL), whether patients welcome being given a
      preference and whether this correlated with formal toxicity scoring. MATERIALS
      AND METHODS: A single-blind, crossover trial, with 72 women with breast cancer
      who had experienced tamoxifen failure. Randomised to either letrozole 2.5 mg or
      anastrozole 1 mg, for 4 weeks, 1 week off, then crossover for 4 weeks. RESULTS:
      Patients were confidently able to choose which drug suited them best (letrozole
      68%, anastrozole 32%; P < 0.01). Fewer patients, when taking letrozole,
      experienced adverse events than when taking anastrozole (43% vs 65%; P = 0.0028).
      QoL was better when patients were taking letrozole than when they took
      anastrozole (P = 0.02). CONCLUSIONS: As toxicity and QoL strongly correlated with
      patient preference for either drug, albeit with a tendency towards letrozole,
      this suggests that patient preference is now a legitimate and useful end point
      for future crossover studies. In routine practice, women would warmly welcome
      extra involvement in the decision-making process via a crossover manoeuvre if
      side-effects develop, whichever aromatase inhibitor is prescribed initially.

PMID- 15490813
TI  - Postoperative residual tumour imaged by contrast-enhanced computed tomography and
      201Tl single photon emission tomography: can they predict progression-free
      survival in high-grade gliomas?
AB  - AIMS: To evaluate if postoperative residual tumour imaged by either computed
      tomography or 201Tl single photon emission tomography (SPECT) carried out
      postoperatively could predict progression-free survival (PFS) in high-grade
      malignant gliomas. MATERIALS AND METHODS: Thirty-three patients with high-grade
      malignant gliomas underwent both contrast-enhanced CT scan and 201Tl-SPECT
      postoperatively before receiving radiotherapy. The PFS was evaluated against the
      individual reports of the above two imaging studies by univariate analysis.
      RESULTS: CT and 201Tl-SPECT were carried out within a median interval of 17 days
      after surgery. Of the 33 patients, CT and 201Tl-SPECT were reported as positive
      for residual tumours in 23 (69.7%) and 30 (91%) patients, respectively.
      Sensitivity, specificity and overall accuracy were 71.4%, 40% and 66.6% for CT,
      and 96.4%, 40% and 87.8% for 201Tl-SPECT, respectively, and were based on their
      last follow-up status (P = 0.627 for CT; P = 0.053 for 201Tl-SPECT). The median
      PFS for patients reported to be positive or negative on CT scan was 4 and 5
      months, respectively (P = 0.202). With 201Tl-SPECT, although the median PFS for
      patients with a positive 201Tl uptake was also 4 months, it had not even reached
      for those reported having a negative 201Tl uptake (cumulative survival 66.7% at
      last follow-up) (P = 0.198). However, Karnofsky performance status (KPS) was the
      only significant predictor on univariate analysis (KPS: < 80 vs. > or = 80; P <
      0.001) for PFS. CONCLUSIONS: Although both the imaging modalities have a poor
      specificity, postoperative 201Tl-SPECT had a significantly better accuracy to
      predict the status at last follow-up than contrast-enhanced CT. Nevertheless, KPS
      remained the most significant outcome predictor for PFS in high-grade malignant
      gliomas.

PMID- 15490814
TI  - Early onset of prostate cancer in a patient with common variable
      immunodeficiency.

PMID- 15490815
TI  - Distant cutaneous metastasis after laparoscopic cholecystectomy in a case of
      unsuspected gallbladder cancer.

PMID- 15490816
TI  - Traumatic neuroma: unusual benign lesion occurring in the mastectomy scar.

PMID- 15490817
TI  - Patterns of thermal deposition in the skull during transcranial focused
      ultrasound surgery.
AB  - The induction of temperature elevation by focused ultrasound is a noninvasive
      surgical technique for destroying tissue. This technique has been used clinically
      in soft tissues such as liver, prostate and breast. It has long been desired to
      extend this technique to noninvasive treatment of brain tumors. Although the
      skull was once thought to be an unsurpassable barrier to focused ultrasound
      treatment, it has been shown that the distortion caused by the skull can be
      corrected to produce a useful intracranial focus. However, the attenuation
      experienced by the ultrasound in passing through cranial bone is large, and
      consequently the skull is subject to the deposition of acoustic energy as heat.
      The nature and extent of this heating process has been difficult to characterize
      empirically. It is practically difficult to implant a sufficient number of
      thermocouples to obtain detailed temperature data directly, and bone is an
      unsuitable medium in which to perform noninvasive thermometry using proton
      chemical shift magnetic resonance imaging. Furthermore, skull specimens used
      experimentally lack active blood perfusion of the skull and the overlying scalp.
      This paper describes the use of large-scale acoustic and thermal simulations to
      calculate the distribution of temperature within the skull and brain that can be
      expected to occur during therapeutically useful focused ultrasound sonications of
      the brain. The results demonstrate that standing waves may be formed within the
      skull during transcranial sonication leading to nonuniform skull heating.
      However, the results also show that these effects can be sufficiently controlled
      to allow therapeutic ultrasound to be focused in the cranial base region of the
      brain without causing thermal damage to the scalp, skull or outer surface of the
      brain.

PMID- 15490818
TI  - Force modeling for needle insertion into soft tissue.
AB  - The modeling of forces during needle insertion into soft tissue is important for
      accurate surgical simulation, preoperative planning, and intelligent robotic
      assistance for percutaneous therapies. We present a force model for needle
      insertion and experimental procedures for acquiring data from ex vivo tissue to
      populate that model. Data were collected from bovine livers using a one-degree-of
      freedom robot equipped with a load cell and needle attachment. computed
      tomography imaging was used to segment the needle insertion process into phases
      identifying different relative velocities between the needle and tissue. The data
      were measured and modeled in three parts: 1) capsule stiffness, a nonlinear
      spring model; 2) friction, a modified Karnopp model; and 3) cutting, a constant
      for a given tissue. In addition, we characterized the effects of needle diameter
      and tip type on insertion force using a silicone rubber phantom. In comparison to
      triangular and diamond tips, a bevel tip causes more needle bending and is more
      easily affected by tissue density variations. Forces for larger diameter needles
      are higher due to increased cutting and friction forces.

PMID- 15490819
TI  - Automated ischemic beat classification using genetic algorithms and multicriteria
      decision analysis.
AB  - Cardiac beat classification is a key process in the detection of myocardial
      ischemic episodes in the electrocardiographic signal. In the present study, we
      propose a multicriteria sorting method for classifying the cardiac beats as
      ischemic or not. Through a supervised learning procedure, each beat is compared
      to preclassified category prototypes under five criteria. These criteria refer to
      ST segment changes, T wave alterations, and the patient's age. The difficulty in
      applying the above criteria is the determination of the required method
      parameters, namely the thresholds and weight values. To overcome this problem, we
      employed a genetic algorithm, which, after proper training, automatically
      calculates the optimum values for the above parameters. A task-specific cardiac
      beat database was developed for training and testing the proposed method using
      data from the European Society of Cardiology ST-T database. Various experimental
      tests were carried out in order to adjust each module of the classification
      system. The obtained performance was 91% in terms of both sensitivity and
      specificity and compares favorably to other beat classification approaches
      proposed in the literature.

PMID- 15490820
TI  - Asymptotic SNR of scalar and vector minimum-variance beamformers for
      neuromagnetic source reconstruction.
AB  - To reconstruct neuromagnetic sources, the minimum-variance beamformer has been
      extended to incorporate the three-dimensional vector nature of the sources, and
      two types of extensions-the scalar- and vector-type extensions-have been
      proposed. This paper discusses the asymptotic signal-to-noise ratio (SNR) of the
      outputs of these two types of beamformers. We first show that these two types of
      beamformers give exactly the same output power and output SNR if the beamformer
      pointing direction is optimized. We then compare the output SNR of the beamformer
      with optimum direction to that of the conventional vector beamformer formulation
      where the beamformer pointing direction is not optimized. The comparison shows
      that the beamformer with optimum direction gives an output SNR superior to that
      of the conventional vector beamformer. Numerical examples validating the results
      of the analysis are presented.

PMID- 15490821
TI  - Noncontact method for sleep stage estimation.
AB  - This paper describes a novel method to estimate sleep stage through noninvasive
      and unrestrained means. The Rechtschaffen and Kales (R-K) method is a standard to
      estimate sleep stage. However, it involves restraining the examinee and, thus,
      induces psychological stress. Furthermore, it requires specialists with a high
      degree of technical expertise and the use of an expensive polygraph. The sleep
      estimation method presented here is based on the noninvasive and unrestrained
      pneumatic biomeasurement method presented by the authors. Sleep stage transition
      in overnight sleep and the relationship between sleep stage and biosignals
      measured using the pneumatic method was analyzed and from the results, a
      mathematical model of sleep was created. Based on this model, a sleep stage
      estimator, including a sleep stage classifier and observer, was designed. The
      sleep state transition equation was the basis for the design of this observer,
      while the observed relationships were the basis for designing a classifier.
      Agreement of the estimated sleep stages with those obtained using the R-K method
      for the non-REM stage was 82.6%, for the REM stage was 38.3 % and for Wake was
      70.5 %, including disagreement. However, the new method might ultimately result
      in better estimation of sleep stage due to the fact that it does not physically
      restrain the patient and does not induce psychological stress.

PMID- 15490822
TI  - Temporal and spatial phase analyses of the electrocardiogram stratify intra
      atrial and intra-ventricular organization.
AB  - We hypothesized that electrocardiogram (ECG) spatial phase analysis would define
      a spectrum of intracardiac organization from atrial fibrillation (AF), nonisthmus
      dependent and isthmus-dependent atrial flutter (AFL) to supraventricular
      tachycardias (SVT), and similarly for ventricular arrhythmias. We analyzed
      arrhythmia ECGs of 33 patients with isthmus (n = 9) and nonisthmus (n = 5)
      dependent AFL and SVT: atrial (n = 3), atrioventricular nodal (n = 3), and
      orthodromic reciprocating (n = 3) tachycardias, as well as AF (n = 5),
      ventricular tachycardia (monomorphic, VT-MM; n = 7), and fibrillation (VF; n =
      3). ECG spatial phase was considered coherent when the correlation coefficient of
      an atrial (or ventricular) template to its ECG over time maintained a constant
      relationship in XY, XZ, and YZ planes. Regularity was quantified spectrally from
      ECG and correlation series. Spatial coherence occurred in 9/9 cases of isthmus-
      but only 1/5 of cases of nonisthmus-dependent AFL (p < 0.01; chi2). All showed
      one dominant spectral peak (temporal coherence). In AF, spatial phase was
      inconsistent in all planes and spectra were broad band. Temporal and spatial
      coherence occurred in other SVT. VT-MM maintained spatial phase and a single
      spectral peak, while VF displayed neither. Our conclusions are that temporal and
      spatial phase analysis from the ECG stratifies intra-atrial and intra-ventricular
      organization and reveals subtle variability lost on visual inspection.

PMID- 15490823
TI  - A new methodology for determining point-of-gaze in head-mounted eye tracking
      systems.
AB  - The ability to determine point-of-gaze with respect to an observed scene provides
      significant insight into human cognitive processes, since shifts in gaze position
      are generally guided by shifts in attentional focus. Using a head-mounted eye
      tracking system, a new methodology based on four or more point correspondences in
      two views was developed to reconstruct the subject's point-of-gaze. For exact
      point correspondences, 95% of the reconstruction errors are less than 0.32
      degrees when the homography algorithm with distortion compensation is used to
      determine gaze position. In a typical visual scanning experiment, 95% of the
      reconstruction errors are less than 0.90 degrees. Analysis of normalization
      techniques that reduce the sensitivity of the homography algorithm to input
      errors suggests that the point correspondences should be arranged in a radially
      symmetric distribution around the area to be scanned. The new methodology was
      used in a clinical study on visual selective attention and mood disorders; this
      study showed that depressed subjects spent significantly more time looking at
      images with dysphoric themes than normal control subjects.

PMID- 15490824
TI  - Bicoherence analysis of new cardiovascular spectral components observed in heart
      transplant patients: statistical approach for bicoherence thresholding.
AB  - Following heart transplant (HT), the patient's heart functions under complete
      cardiac denervation. As a result, the variability in physiologic signals is
      extremely reduced. We have previously reported that in addition to the typical
      spectral components (of very low amplitude), part of the HT patients (above 50%)
      demonstrated unexpected additional peaks in their heart rate and blood pressure
      spectra. These peaks may be a result of the development of compensatory mechanism
      induced by loss of parasympathetic control, or of increased importance of
      nonlinear control interactions. It is important to quantify these strange,
      unexpected very-high frequency (VHF) peaks, to understand their origin and their
      contribution to cardiac control in transplant patients. In this paper, we chose
      to examine these VHF peaks by applying the bicoherence approach. The reduced
      signal to noise ratio, occurring in these patients, results, however, in an
      extremely noisy bicoherence. We, therefore, developed several statistical tools
      in order to distinguish between "true" bicoherence peaks (reflecting true phase
      coupling) and spurious peaks. The outcome of these methods was an efficient and
      sensitive bicoherence thresholding procedure, able to identify most of the
      spurious peaks. Applying these tools to the bicoherence of cardiovascular signals
      which display VHF peaks, revealed several significant bicoherence peaks.
      Interestingly, these peaks consisted of two different types. The first type of
      VHF peaks simply reflects nonlinear cardiac-respiratory coupling, imposed by
      nonsinusoidal breathing. The second type, however, is clearly not induced by the
      respiratory system. We believe that these type-2 VHF peaks reflect the evolution
      of a new, yet unexplained, compensatory mechanism.

PMID- 15490825
TI  - Detection of skin cancer by classification of Raman spectra.
AB  - Skin lesion classification based on in vitro Raman spectroscopy is approached
      using a nonlinear neural network classifier. The classification framework is
      probabilistic and highly automated. The framework includes a feature extraction
      for Raman spectra and a fully adaptive and robust feedforward neural network
      classifier. Moreover, classification rules learned by the neural network may be
      extracted and evaluated for reproducibility, making it possible to explain the
      class assignment. The classification performance for the present data set,
      involving 222 cases and five lesion types, was 80.5%+/-5.3% correct
      classification of malignant melanoma, which is similar to that of trained
      dermatologists based on visual inspection. The skin cancer basal cell carcinoma
      has a classification rate of 95.8%+/-2.7%, which is excellent. The overall
      classification rate of skin lesions is 94.8%+/-3.0%. Spectral regions, which are
      important for network classification, are demonstrated to reproduce. Small
      distinctive bands in the spectrum, corresponding to specific lipids and proteins,
      are shown to hold the discriminating information which the network uses to
      diagnose skin lesions.

PMID- 15490826
TI  - A recursive algorithm for the three-dimensional imaging of brain electric
      activity: Shrinking LORETA-FOCUSS.
AB  - Estimation of intracranial electric activity from the scalp electroencephalogram
      (EEG) requires a solution to the EEG inverse problem, which is known as an ill
      conditioned problem. In order to yield a unique solution, weighted minimum norm
      least square (MNLS) inverse methods are generally used. This paper proposes a
      recursive algorithm, termed Shrinking LORETA-FOCUSS, which combines and expands
      upon the central features of two well-known weighted MNLS methods: LORETA and
      FOCUSS. This recursive algorithm makes iterative adjustments to the solution
      space as well as the weighting matrix, thereby dramatically reducing the
      computation load, and increasing local source resolution. Simulations are
      conducted on a 3-shell spherical head model registered to the Talairach human
      brain atlas. A comparative study of four different inverse methods, standard
      Weighted Minimum Norm, L1-norm, LORETA-FOCUSS and Shrinking LORETA-FOCUSS are
      presented. The results demonstrate that Shrinking LORETA-FOCUSS is able to
      reconstruct a three-dimensional source distribution with smaller localization and
      energy errors compared to the other methods.

PMID- 15490827
TI  - Computerized tongue diagnosis based on Bayesian networks.
AB  - Tongue diagnosis is an important diagnostic method in traditional Chinese
      medicine (TCM). However, due to its qualitative, subjective and experience-based
      nature, traditional tongue diagnosis has a very limited-application in clinical
      medicine. Moreover, traditional tongue diagnosis is always concerned with the
      identification of syndromes rather than with the connection between tongue
      abnormal appearances and diseases. This is not well understood in Western
      medicine, thus greatly obstruct its wider use in the world. In this paper, we
      present a novel computerized tongue inspection method aiming to address these
      problems. First, two kinds of quantitative features, chromatic and textural
      measures, are extracted from tongue images by using popular digital image
      processing techniques. Then, Bayesian networks are employed to model the
      relationship between these quantitative features and diseases. The effectiveness
      of the method is tested on a group of 455 patients affected by 13 common diseases
      as well as other 70 healthy volunteers, and the diagnostic results predicted by
      the previously trained Bayesian network classifiers are reported.

PMID- 15490828
TI  - Automatic tracking, feature extraction and classification of C elegans
      phenotypes.
AB  - This paper presents a method for automatic tracking of the head, tail, and entire
      body movement of the nematode Caenorhabditis elegans (C. elegans) using computer
      vision and digital image analysis techniques. The characteristics of the worm's
      movement, posture and texture information were extracted from a 5-min image
      sequence. A Random Forests classifier was then used to identify the worm type,
      and the features that best describe the data. A total of 1597 individual worm
      video sequences, representing wild type and 15 different mutant types, were
      analyzed. The average correct classification ratio, measured by out-of-bag (OOB)
      error rate, was 90.9%. The features that have most discrimination ability were
      also studied. The algorithm developed will be an essential part of a completely
      automated C. elegans tracking and identification system.

PMID- 15490829
TI  - Combining strings and necklaces for interactive three-dimensional segmentation of
      spinal images using an integral deformable spine model.
AB  - Segmentation of the spine directly from three-dimensional (3-D) image data is
      desirable to accurately capture its morphological properties. We describe a
      method that allows true 3-D spinal image segmentation using a deformable integral
      spine model. The method learns the appearance of vertebrae from multiple
      continuous features recorded along vertebra boundaries in a given training set of
      images. Important summarizing statistics are encoded into a necklace model on
      which landmarks are differentiated on their free dimensions. The landmarks are
      used within a priority segmentation scheme to reduce the complexity of the
      segmentation problem. Necklace models are coupled by string models. The string
      models describe in detail the biological variability in the appearance of spinal
      curvatures from multiple continuous features recorded in the training set. In the
      segmentation phase, the necklace and string models are used to interactively
      detect vertebral structures in new image data via elastic deformation reminiscent
      of a marionette with strings allowing for movement between interrelated
      structures. Strings constrain the deformation of the spine model within feasible
      solutions. The driving application in this work is analysis of computed
      tomography scans of the human lumbar spine. An illustration of the segmentation
      process shows that the method is promising for segmentation of the spine and for
      assessment of its morphological properties.

PMID- 15490830
TI  - Multislice tomographic imaging and analysis of human breast-equivalent phantoms
      and biological tissues.
AB  - A laser transillumination tomographic system, consisting of electrical, optical,
      mechanical, and software components, to obtain multislice images of tissue
      equivalent breast phantoms and biological tissues, is developed. The tissue
      equivalent phantoms are prepared from paraffin wax mixed with wax color pigments
      by matching their surface backscattered profiles as measured by multiprobe laser
      reflectometer, with that of respective tissues. The optical parameters of these
      phantoms are determined by matching their reflectance profiles with that as
      obtained by Monte Carlo simulation of optical scattering. For multislice
      tomographic analysis conical breast phantoms of height 80.0 mm and 80.0 mm base
      diameter with inclusions of different optical properties and dimensions are
      developed. The resolution of the inclusions in the tomograms depends on their
      sizes and optical parameters. The minimum size of the inclusion as detected by
      this procedure in a slice of diameter 50.0 mm is 3.0 mm. The structural variation
      as observed in the tomograms of phantoms of combination of biological tissues
      indicates its possible applications in detecting the abnormalities developing in
      human healthy soft tissues.

PMID- 15490831
TI  - A probe for organ impedance measurement.
AB  - In this paper, we describe the theory and practical implementation of an
      electrical impedance probe for making in vivo measurements of the electrical
      admittance of living tissue. The probe uses concentric annular electrodes and is
      shown to sample a more localized, yet greater, volume of tissue than the standard
      four-electrode probe. We have developed a mathematical model for the conduction
      of current between the probe electrodes assuming that we are investigating a
      uniform, isotropic, semi-infinite region and taking into account the contact
      impedance between the electrodes and the organ. The electric fields produced by
      the probe have been calculated by solving a weakly singular Fredholm integral
      equation of the second kind. The size and position of the probe electrodes have
      been optimized to maximize both the accuracy in the admittance measurement and
      insensitivity to contact impedance. A probe and driving hardware have been
      constructed and experimental results are provided showing the accuracy of
      admittance measurements at 50 and 640 KHz.

PMID- 15490833
TI  - Modeling of elastic modulus evolution of cirrhotic human liver.
AB  - A micromechanics-based composite model is developed for the elastic behavior and
      its modulus evolution of cirrhotic human liver correlated with different
      pathological stages. Microstructurally, the cirrhotic liver is hypothesized to be
      pathologically elastic nodules embedded in the soft tissue matrix whose
      hyperelastic behavior is controlled by the Veronda-Westmann model. Under finite
      deformation, the total strain energy of the liver is collected through the
      combination of that in nodule particles and that in the tissue matrix. The
      overall constitutive relation of the pathological liver can further be
      established through the nonlinear hyperelasticity theory. Predictions of the
      elastic modulus and its pathological evolution are compared with available
      experimental data.

PMID- 15490832
TI  - A microelectrode/microelectronic hybrid device for brain implantable
      neuroprosthesis applications.
AB  - We have designed, fabricated, and characterized a microminiaturized "neuroport"
      for brain implantable neuroprosthesis applications, using an analog CMOS
      integrated circuit and a silicon based microelectrode array. An ultra-low power,
      low-noise CMOS preamplifier array with integral multiplexing was designed to
      accommodate stringent thermal and electrophysiological requirements for
      implantation in the brain, and a hybrid integration approach was developed to
      fabricate a functional microminiaturized neuroprobe device. Measurements showed
      that our fully scalable 16-channel CMOS amplifier chip had an average gain of 44
      dB, bandwidth from 10 Hz to 7.3 kHz, and an equivalent input noise of
      approximately 9 microVrms with an average power consumption per preamplifier of
      52 microW, which is consistent with simulation results. As a proof-of-concept
      demonstration, we have measured local field potentials from thalamocortical brain
      slices of rats, showing oscillatory behavior with an amplitude about 0.5 mV and a
      period ranging 80-120 ms. The results suggest that the hybrid integrated
      neuroport can form a prime platform for the development of a next level
      microminiaturized neural interface to the brain in a single implantable unit.

PMID- 15490834
TI  - Control of state transitions in an in silico model of epilepsy using small
      perturbations.
AB  - We propose the use of artificial neural networks in an in silico epilepsy model
      of biological neural networks: 1) to predict the onset of state transitions from
      higher complexities, possibly chaotic to lower complexity possibly rhythmic
      activities; and 2) to restore the original higher complexity activity. A coupled
      nonlinear oscillators model (Bardakjian and Diamant, 1994) was used to represent
      the spontaneous seizure-like oscillations of CA3 hippocampal neurons (Bardakjian
      and Aschebrenner-Scheibe, 1995) to illustrate the prediction and control schemes
      of these state transition onsets. Our prediction scheme consists of a recurrent
      neural network having Gaussian nonlinearities. When the onset of lower complexity
      activity is predicted in the in silico model, then our control scheme consists of
      applying a small perturbation to a system variable (i.e., the transmembrane
      voltage) when it is sufficiently close to the unstable higher complexity
      manifold. The system state can be restored back to its higher complexity mode
      utilizing the forces of the system's vector field.

PMID- 15490835
TI  - Lesion size estimator of cardiac radiofrequency ablation at different common
      locations with different tip temperatures.
AB  - Finite element method (FEM) analysis has become a common method to analyze the
      lesion formation during temperature-controlled radiofrequency (RF) cardiac
      ablation. We present a process of FEM modeling a system including blood,
      myocardium, and an ablation catheter with a thermistor embedded at the tip. The
      simulation used a simple proportional-integral (PI) controller to control the
      entire process operated in temperature-controlled mode. Several factors affect
      the lesion size such as target temperature, blood flow rate, and application
      time. We simulated the time response of RF ablation at different locations by
      using different target temperatures. The applied sites were divided into two
      groups each with a different convective heat transfer coefficient. The first
      group was high-flow such as the atrioventricular (AV) node and the atrial aspect
      of the AV annulus, and the other was low-flow such as beneath the valve or inside
      the coronary sinus. Results showed the change of lesion depth and lesion width
      with time, under different conditions. We collected data for all conditions and
      used it to create a database. We implemented a user-interface, the lesion size
      estimator, where the user enters set temperature and location. Based on the
      database, the software estimated lesion dimensions during different applied
      durations. This software could be used as a first-step predictor to help the
      electrophysiologist choose treatment parameters.

PMID- 15490836
TI  - [Salmonella enterica serotypes and Salmonella infections: a multicenter study
      covering ten provinces in Turkey].
AB  - In order to find the distinctive features of Salmonellae and Salmonella
      infections in Turkey, 620 Salmonellae strains, isolated from various clinical
      samples (481 stool, 108 blood, 12 urine, 3 bone marrow, 3 cerebrospinal fluid, 9
      pus, and one from each of the bile, pleural fluid, wound, catheter samples) in 13
      clinical microbiology laboratories of 10 provinces in Turkey (Ankara, Antalya,
      Bursa, Edirne, Eskisehir, Istanbul, Izmir, Kayseri, Konya and Trabzon) between
      July 1, 2000 and June 30, 2002, were serotyped. Among the patients 43% were
      female, 57% were male, 63.2% were from outpatient clinics and 36.8% were
      hospitalized patients. Seventy eight percent of the patients had gastroenteritis,
      10.7% had septicemia/local infection, 9.8% had typhoid/paratyphoid fever and 1.5%
      were carriers. Incidence of gastroenteritis was higher in 0-5 years age group
      (p<0.001). Of the 620 Salmonella enterica isolates, 47.7% were S. Enteritidis,
      34.7% S. Typhimurium, 6% S. Paratyphi B, 2.9% S. Typhi, 0.2% S. paratyphi A, 6.1%
      serogroup C1, and 2.4% serogroup C2. S. Enteritidis was the most common serotype
      in all provinces except for Kayseri, where S. Typhimurium was found to be the
      most common serotype (68.2%). Overall, the most frequently isolated serotype was
      S. Enteritidis, also being the most common serotype in stool and blood cultures.
      During the surveillance period two outbreaks have occurred, the first one by S.
      Enteritidis strains in Edirne, and the second one by S. Typhimurium strains in
      Kayseri. As a result, Salmonella infections are still a common health problem in
      Turkey, and active surveillance of Salmonella infections has vital importance.

PMID- 15490837
TI  - [Species and biovar distribution of Brucella isolates in Trakya University
      Hospital between 1997-2002].
AB  - The aim of this study was to evaluate the species and biovar distribution of
      Brucella spp. isolated from blood cultures in Clinical Microbiology Laboratory of
      Trakya University Hospital, between 1997-2002. A total of 48 Brucella spp. have
      been isolated from 14.815 patients (0.3%), and the strains were identified
      according to CO2 requirement, H2S production, basic fuchsin and thionin
      sensitivity, lysis by Tbilisi phages, and presence of agglutination with
      monospecific A and M antisera. As a result, 47 (97.9%) isolates were identified
      as B. melitensis, and one as B. abortus (2.1%). Forty two (89.4%) of B.
      melitensis isolates were biovar 3, and five (10.6%) were biovar 1, while the
      single isolate of B. abortus was identified as an atypical strain.

PMID- 15490838
TI  - [Comparison of Cobas Amplicor system and microscopic examination with bactec
      radiometric method for the detection of Mycobacterium tuberculosis in clinical
      samples].
AB  - Tuberculosis is still a major health problem all around the world. Since the
      patients with tuberculosis spread the infection by means of aerosols containing
      tuberculosis bacilli, it is critically important to detect these patients and
      start the treatment as soon as possible. Therefore there is a need for highly
      sensitive and specific reliable diagnostic methods. In this study, Ehrlich-Ziehl
      Neelsen (EZN) staining method and Cobas Amplicor system were evaluated for the
      diagnosis of tuberculosis in comparison with the standard reference Bactec
      radiometric method. A total of 2098 clinical samples collected between July 2002
      and February 2004 in Clinical Microbiology Laboratory of Hacettepe University
      Adult Hospital, were studied by Bactec radiometric system for diagnosis of
      tuberculosis and M. tuberculosis was detected in 107 (5.1%) samples. The
      specificity, sensitivity, positive and negative predictive values of EZN staining
      method were found to be 98.5%, 42.9%, 62.1% and 96.9%, respectively. The
      specificity, sensitivity, positive and negative predictive values of Cobas
      Amplicor system were detected as 99.3%, 67.3%, 83.5% and 98.4%, respectively.
      These results were in concordance with the results of previous studies. In
      conclusion, microscopic examination and nucleic acid amplification methods should
      always be used together with culture methods for the laboratory diagnosis of
      tuberculosis.

PMID- 15490839
TI  - [The resistance rates of Mycobacterium tuberculosis strains to antituberculosis
      drugs: evaluation of two years' data in Aegean region, Turkey].
AB  - The aim of this study was to determine the primary, secondary and total
      resistance rates of Mycobacterium tuberculosis strains in the Aegean Region,
      Turkey, between November 1st 1999 and November 30th 2001. A total of 490 M.
      tuberculosis strains isolated from patients admitted to 27 different tuberculosis
      dispensaries, were evaluated. The isolates have been identified as Mycobacterium
      tuberculosis with the colony morphology, growth rate and standard biochemical
      tests, and their sensitivities to isoniazid, rifampicin and ethambutol were
      tested by using indirect proportion method. H37Rv, ATCC 35838 and ATCC 35825 were
      used as standard control strains. Clinical information could be obtained about
      474 patients and it has been detected that 387 (81.6%) of them received no prior
      antituberculous therapy, while 87 of them (18.4%) received antituberculous
      therapy longer than one month. Primary, secondary and total resistance rates to
      one or more drugs was found as 18.4%, 32.2% and 20.9%, respectively. Primary,
      secondary and total resistance rates for isoniazid (INH) and rifampicin (R) were
      found as follows, respectively; 12.4%, 26.4%, 14.9% and 5.7%, 19.5%, 8.2%.
      Primary resistance rate against INH+R were found 4.4%, secondary resistance rate
      were 17.2% and total resistance rate were 6.8%, in the multi-drug resistant
      isolates. According to these results it could be concluded that, drug resistance
      which requires immediate solution, continues to be a major problem in our region.

PMID- 15490840
TI  - [The presence of Chlamydophila pneumoniae, Helicobacter pylori and
      cytomegalovirus in human atherosclerosis detected by molecular and serological
      methods].
AB  - Persistant infections due to Chlamydophila pneumoniae, Helicobacter pylori, and
      Cytomegalovirus are suggested to contribute to the development of
      atherosclerosis. In this study, the presence of these agents was investigated by
      polymerase chain reaction (PCR) and serological tests in atherosclerotic plaques
      and non-atherosclerotic vessel samples. Thirty-three specimens from the
      atherosclerotic plaques (lesion group), 45 specimens from the healthy left
      internal mammarian arteries and ascending aortas of the atherosclerotic patients
      (non-lesion group), and 15 specimens from the aortas of non-atherosclerotic
      patients as determined by angiography (control group), were included to the
      study. Serum samples were also collected from all study subjects for the
      serological investigation. PCR and ELISA were used in order to determine the
      nucleic acid positivity and IgG titers, respectively. C. pneumoniae and H. pylori
      DNA were found in 6 (18.1%) and 14 (42.4%) of the lesion group, 2 (4.4%) and 9
      (20%) of the non-lesion group, respectively. CMV DNA was not found in either
      groups. All of the PCR results of control group were negative. C. pneumoniae IgG
      was found positive in one case of the lesion group (3%) and three cases of the
      non-lesion group (6.7%). H. pylori IgG were positive in all the subjects except
      for three patients who were in the non-lesion group. The presence of C.
      pneumoniae and H. pylori DNA in a considerable number of lesion and non-lesion
      groups' specimens, but absence in control group specimens supports the hypothesis
      that these agents have an association with atherosclerosis.

PMID- 15490842
TI  - [Investigation of herpes simplex virus DNA by real-time polymerase chain reaction
      in the clinical samples].
AB  - The aim of this study was to investigate the presence of Herpes simplex virus
      (HSV) type 1 and type 2 DNA from the clinical samples sent to our routine
      laboratory, by real-time polymerase chain reaction (PCR). A total of 328 samples
      collected from 306 female and 7 male patients who were admitted to different
      outpatient clinics were included in the study. The samples included 235 cervical
      swab samples (of which 150 were from pregnant women), 77 amniotic fluid, 8 blood,
      6 cerebrospinal fluid (CSF), one pericardial fluid and one cervical biopsy. DNA
      extraction were performed with High Pure Viral Nucleic Acid Kit (Roche, Germany)
      and amplified in Light Cycler (Roche, Germany) with a commercial amplification
      mix (Metis Biotechnology, Ankara). HSV-DNA positivity were found in 2.1% of the
      cervical samples (three of 150 pregnant and two of 85 non-pregnant women), two of
      the blood samples and one of the CSF sample, while there were no positive result
      for the other clinical specimens. It can be concluded that, real-time PCR would
      be preferred in conditions requiring rapid diagnosis such as HSV infections of
      central nervous system and HSV suspected infections of immunosupressed patients,
      as a rapid and practical method.

PMID- 15490841
TI  - [Investigation of human papillomavirus DNA in cervical specimens by hybrid
      capture assay].
AB  - The aim of this study was to investigate the presence of human papillomavirus DNA
      (HPV-DNA) in cervical specimens of those randomly selected women, age between 18
      62 years and applied to Gynecology and Obstetric Clinics in a six months period.
      Two hundred and six women were enrolled during the study. HPV-DNA in the cervical
      specimens were investigated with Hybrid Capture System (Digene Hybrid Capture
      System, UK) and also the cytologic specimens were examined simultaneously. HPV
      DNA positivity was 4.9% overall. HPV-DNA positivity was found to be higher among
      younger population (30-39 age group: 7.3%), women with lower education level (6.9
      %) and with lower income level (11.8%). Additionally, HPV-DNA positivity rate was
      found higher among women who experienced their first sexual intercourse at lower
      ages (15-19 age group: 6.3%) and who use oral contraceptives (7.7%). HPV-DNA
      positivity was found to be 2.1% in women with normal cervical cytology and 42.9%
      in women with epithelial cell abnormalities, and this difference was
      statistically significant (p=0.000). The presence of HPV together with high rates
      of epithelial cell abnormalities leading to cervical cancer, supported the
      association between HPV and malignancy. Thus, HPV-DNA testing should be included
      in the cervical cancer screening programmes.

PMID- 15490843
TI  - [A novel T-cloning vector system].
AB  - The use of cloning vectors has revolutionized molecular biology. Any vector with
      appropriate cloning sites can be used to clone a section of DNA and polymerase
      chain reaction (PCR) is a useful method for producing DNA fragments that are
      intended to be cloned. When Taq polymerase is used in PCR for polymerization, the
      enzyme adds an extra adenosyl (A) nucleotide to the 3' end of the extended
      strand, in a template independent manner. T-cloning vectors are created by adding
      a thymidine (T) residue to the ends of the cloning site. This aids ligation with
      PCR products possessing A-T. In this study, we prepared a T-cloning vector
      system, which guarantees insertion of open reading frames to the right position
      for expression. This method provides an easy way of cloning PCR products assuring
      at the same time in frame insertion.

PMID- 15490845
TI  - [Case report: subdural hemorrhage in neurobrucellosis].
AB  - In this report, a 49-year-old female patient who were diagnosed as
      neurobrucellosis by the clinical, bacteriologic and serologic findings, has been
      presented. The case deserved presentation and discussion since it presented with
      subdural hemorrhage which is a rare complication of neurobrucellosis.

PMID- 15490844
TI  - [Application of in-house enzyme immunoassay and indirect hemagglutination methods
      for the serologic diagnosis of cystic echinococcosis].
AB  - It is necessary to use methods that are not only fast and easily applicable, but
      also safe in the diagnosis of cystic echinococcosis (CE) and monitoring the
      treatment. In the present study, we investigated the presence of specific
      Echinococcus granulosus antibodies by in-house enzyme immunoassay (ELISA) and
      indirect hemagglutination (IHA) tests in the sera of 64 patients who were
      surgically confirmed to have CE, 10 patients with various lung and liver
      malignancies and 20 patients with Hymenolepis nana infections. Of the 64 CE
      patients, 52 (81.2%) were found to be positive with IHA and 49 (76.5%) were found
      to be positive with ELISA (in both of the tests, > or =1/64 titers were accepted
      as positive), while none of the other patient groups yielded positive results. As
      a result, the sensitivities of in-house IHA and ELISA methods were determined to
      be 81.2% and 76.5%, respectively, whereas the specificities were 100% for both of
      the tests. There was no statistically significant difference between the methods
      for the detection of E. granulosus antibodies (p>0.05). It can be concluded that,
      the agreement between the methods could make a considerable contribution in the
      diagnosis and postoperative follow-up of the CE patients.

PMID- 15490846
TI  - [Case report: nosocomial Ralstonia pickettii infection in neonatal intensive care
      unit].
AB  - Although Ralstonia pickettii was known as a saprophytic species, it has been
      isolated in nosocomial infections in recent years. In this case report, R.
      pickettii infection of a neonate in the neonatal intensive care unit (ICU) was
      presented. R. pickettii was isolated from the blood cultures of the neonate and
      also from the incubator and distilled water of the incubator. The isolates
      revealed identical biochemical and physiological characteristics. The strains
      were identified by conventional tests and by API ID32 GN system. There was no
      other newborn infected by R. pickettii in the ICU during the same period. In
      conclusion, R. picketti should be taken into consideration as an etiologic agent
      especially in ICU infections. To prevent outbreaks, sterile solutions used for
      patient care and other possible sources must be investigated regularly.

PMID- 15490847
TI  - [Meningitis due to Pseudomonas stutzeri: a case report].
AB  - Pseudomonas stutzeri is a saprophytic microorganism that rarely causes severe
      infections. In this report, a 28 days old male patient with meningomyelocele at
      birth was presented. The patient was admitted to the hospital with fever, and
      diagnosed as meningitis on the basis of physical examination and leukocytosis
      (blood: 16.380/mm3, cerebrospinal fluid (CSF): 130/mm3; 90% PMNL). Following
      diagnosis ceftriaxone therapy was started led to improvement in clinical and
      laboratory findings. However on the 20th day, the clinical signs and symptoms
      became worse, and the patient was diagnosed to develop a second meningitis attack
      by laboratory examination of CSF. P. stutzeri was isolated from the CSF culture,
      and the isolate was found to be resistant to ceftriaxone. Upon this result the
      therapy has changed to meropenem. On the 5th day of the therapy, the patient has
      slightly improved and he was discharged due to the wishes of his parents, however
      he died two days after discharge. This first case of P. stutzeri meningitis in
      neonates was presented to withdraw attention to this clinical entity.

PMID- 15490849
TI  - [Bacterial communication: quorum-sensing].
AB  - The interaction between the host and a pathogenic bacterium is mainly controlled
      by the bacterial population size. An individual bacterial cell is able to sense
      other members of the same species and in response, differentially expresses
      specific genes. Such cell to cell communication is called quorum sensing (QS) and
      involves the direct or indirect activation of a response regulator by a signal
      molecule. The major QS signal molecules are N-acyl homoserine lactones in Gram
      negative bacteria and post-translationally modified peptides in Gram positive
      bacteria. QS system is used by a wide variety of bacteria including human
      pathogens. QS genes are important for the pathogenic potential of Pseudomonas
      aeruginosa and Staphylococcus aureus, as well as other invasive bacteria. Thus QS
      interfering molecules promise new therapeutic strategies or prophylactic measures
      in infectious diseases. In this review article, the role of QS system on
      bacterial virulence, its effects on the host immune response and QS inhibitors
      for prophylaxis and therapy are discussed.

PMID- 15490848
TI  - [Case report: a Fusarium fungaemia].
AB  - In this report, a case of Fusarium fungaemia developed in an acute lymphoblastic
      leukemia (ALL) patient was presented. A seven year old girl who had weakness,
      loss of appetite, paleness and ecchymosis on legs applied to Pediatric Hematology
      Service and cytotoxic chemotherapy was started after she had been diagnosed as
      ALL-L1. Her chemotherapy was stopped because of increase in fever, leukopenia and
      neutropenia. Central venous catheter and peripheral blood cultures were obtained.
      Fusarium thapsinum was recovered from blood cultures, obtained in two consecutive
      days. Thereupon central venous catheter of the patient was removed and
      intravenous amphotericin B was added to the therapy. On the fifth day of febrile
      neutropenia attack, her fever was decreased after the onset of antifungal
      therapy. Radiological examinations were normal and no fungal growth was observed
      in the later blood cultures. On the 21st day of amphotericin B therapy,
      chemotherapy was started again and amphotericin B was changed to peroral
      itraconazole (200 mg/day) at the fifth week. The patient whose itraconazole
      therapy was stopped after three months, was still in remission and continued
      receiving her prolonged therapy. In conclusion, Fusarium infections which
      manifest with fungaemia and fever as the only symptoms, should be taken into
      consideration in neutropenic patients receiving immunosuppressive therapy.

PMID- 15490850
TI  - [RNA interference: mechanism and applications].
AB  - Gene expression in eukaryotes is controlled at transcriptional and post
      transcriptional levels by RNA dependent mechanism called as "RNA Interference" or
      "RNA Inhibition". Small inhibitory RNAs (siRNAs) formed by the cleavage of double
      stranded RNAs activate the mechanisms which control cellular activities in
      organisms as diverse as protozoa, fungi, plants and primates. RNA interference
      participates in cellular functions such as heterochromatin formation, controlled
      DNA elimination, defence against foreign nucleic acids, maintenance of expression
      patterns via conserved proteins. Its effect is also generalized and amplified in
      some organisms. RNA interference is widely used as a biotechnological method for
      gene function studies and can also be potentially employed as a gene therapy
      approach for certain autoimmune, neoplastic and infectious diseases. In this
      review, the mechanism of RNA interference and its therapeutic applications have
      been discussed, focusing on viral diseases.

PMID- 15490851
TI  - [Immunopathogenesis of Legionnaires' disease].
AB  - Legionella pneumophila, the causative agent of Legionnaires' disease, is a
      facultative intracellular pathogen of alveolar macrophages, alveolar epithelial
      cells and, blood monocytes. Infection begins with the inhalation of the
      L.pneumophila. Once the bacteria reach to alveolar spaces, they come in contact
      with the alveolar macrophages, phagocyted and the macrophage takes the bacteria
      into a phagosome. Inside the cell, Legionella inhibits the lysosome-phagosome
      fusion, resulting in multiplication and lysis of the cell. The newly formed
      bacteria infect the other cells. In-vitro studies have shown that the presence of
      antibody and complement do not enhance intracellular killing. Cellular immunity
      is more important than humoral immunity for resolution of Legionella infections.
      In this review article, immunopathogenesis of Legionella infections have been
      discussed under the light of literature.

PMID- 15490852
TI  - [Integrons].
AB  - The development of antimicrobial resistance has led to the discovery of many
      natural mobile elements like transposons and conjugative plasmids. Integrons are
      carried on plasmids and transposons that potentially increase the dissemination
      of antibiotic resistance genes among bacterial species. Integrons are genetic
      elements containing the determinants of a site-specific recombination system.
      These DNA elements mediate the integration of antibiotic resistance genes into
      bacteria through the site-specific recombination. Integrons consist of an
      integrase gene (intl), a recombination site (attl), and one or two promoters
      responsible for expression of the inserted gene cassettes. Class 1 integrons are
      the most commonly studied and largely implicated type in the dissemination of
      antibiotic resistance among clinical isolates. In the last few years, a variety
      of new gene cassettes coding antibiotic resistance have been described. Having
      the ability of horizontal transfer of antibiotic resistance genes between
      interspecies of bacteria, integrons play a dominant role in the development of
      multiresistance in Enterobacteriaceae. In this review article, classification,
      structure and expression, epidemiology and clinical importance of integrons, has
      been discussed.

PMID- 15490853
TI  - [Morphologic structures and identification of dark (dematiaceous) fungi].
AB  - Dematiaceous fungi are dark brown, olivaceous or black pigmented groups of fungi.
      As only and shared characteristic, they belong to the class of Deuteromycetes,
      order Moniliales, genus Hyphomycetes, and they produce melanin or
      dihydroxinaphtalene-melanin. Their identification is mainly based on their
      morphological structure. In this review article, some microscopic properties and
      differentiation criteria have been discussed for the morphological identification
      of these fungi.

PMID- 15490854
TI  - [Laboratory acquired brucellosis].

PMID- 15490855
TI  - The crazy aunt in the attic.

PMID- 15490856
TI  - Sara Reed Stinchcomb, MD.

PMID- 15490857
TI  - Mucoid degeneration of the anterior cruciate ligament: a case report.
AB  - Mucoid degeneration of the ACL is an unusual entity that has only been recently
      described. The imaging features of this entity have been described to a
      sufficient degree to provide diagnostic criteria, and its appearance can be
      characteristic. It is important to recognize this entity as a chronic process as
      its presentation and appearance can mimic a tear of the ACL. The etiology of
      mucoid degeneration of the ACL is unclear, but it may represent part of a
      continuum between early degeneration of the collagen fibrils of the ACL and frank
      formation of a ganglion cyst. The mucoid degeneration usually produces symptoms
      similar to those of an intra-articular mass, but pain may also be associated with
      this process. Treatment may require partial or complete resection of the ACL, but
      percutaneous aspiration of the fluid components of the affected ACL may also be
      effective at alleviating the associated symptoms.

PMID- 15490858
TI  - Smoking in bars and restaurants.

PMID- 15490859
TI  - Basilar artery thrombosis.

PMID- 15490860
TI  - In Oklahoma, a good deed will go unpunished: new protection for volunteers.

PMID- 15490861
TI  - Money is often the motivator.

PMID- 15490862
TI  - H.B. 2661: is it going to divide us or unite us?

PMID- 15490863
TI  - Patient safety and voluntary incident reporting in pediatric oncology.

PMID- 15490864
TI  - Improving pediatric chemotherapy safety through voluntary incident reporting:
      lessons from the field.
AB  - BACKGROUND: A multidisciplinary team within Vanderbilt Children's Hospital (VCH)
      designed, developed, and implemented a pediatric chemotherapy incident reporting
      and improvement system (CIRIS) for pediatric oncology nurse and pharmacists. The
      aim of this collaboration was to improve pediatric chemotherapy by translating
      recommendations made by the Institute of Medicine into an operational safety
      improvement system that is embedded into daily care processes. METHODS: CIRIS
      improves chemotherapy safety by linking two distinct components: (a) a technical
      component that uses desktop, laptop, and portable wireless handheld computers to
      interface the Web-based software application for point-of-care incident reporting
      and on-demand retrieval of patient support information, and (b) a human component
      that performs process analysis, data reporting, and clinical improvement. This
      integrated system facilitates and supports a blame-free culture for reporting of
      near misses and preventable adverse drug events. RESULTS: Between February 8,
      2002, and March 9, 2003, pediatric oncology nurses and chemotherapy pharmacists
      electronically reported 97 chemotherapy-related incidents associated with 96
      unique patients. Ordering errors were the most commonly reported incidents. CIRIS
      improved reporting performance demonstrated using the conventional paper-based
      reporting system.

PMID- 15490865
TI  - Quality of life among children with sickle cell disease receiving chronic
      transfusion therapy.
AB  - Sickle cell disease (SCD) is a genetic disorder that is most prevalent among
      those of African American and Mediterranean descent. Hemoglobin SS is the most
      severe form of SCD and carries an increased risk for stroke. Although the initial
      treatment for stroke is an exchange transfusion, the use of routine, chronic
      transfusion therapy (CTT) has been shown to help prevent this neurological
      injury. The treatment plan is rigorous and time consuming, both of which impact
      one's quality of life (QoL). The purpose of this study was to explore QoL, from
      the child's perspective, as it is affected by CTT Semistructured interviews were
      performed on 10 children undergoing CIT: Five themes emerged from the data: (a)
      pain, (b) school issues, (c) disease knowledge, (d) transfusion therapy, and (e)
      having a stroke. Data from this study reveal that CTT does have an impact on QoL.
      This information is important to share with those making CTT treatment decisions.

PMID- 15490866
TI  - A survey of self-care and dependent-care advice given by pediatric oncology
      nurses.
AB  - This article reports a survey of the current practices of pediatric oncology
      nurses in advising patients and families about symptom reporting and self-care
      interventions. A questionnaire was mailed to 1000 pediatric oncology nurses
      requesting information about age, years of experience in nursing and pediatric
      oncology nursing, current work setting, and professional position. Recipients
      were asked about their practices for advising patients and their families about
      self-care measures and reporting of adverse symptoms. Analysis of 135 valid
      responses showed evidence of both consensus and variability in nursing practice,
      with variability being partly attributable to differences in nurses'work settings
      (inpatient vs. outpatient) and differences in experience level. There was good
      consensus on nurses' recommending of several self-care interventions for eight
      common adverse symptoms and for advice that patients should promptly report to
      health providers certain symptoms or events.

PMID- 15490867
TI  - A comparison of calorie and protein intake in hospitalized pediatric oncology
      patients dining with a caregiver versus patients dining alone: a randomized,
      prospective clinical trial.
AB  - Hospitalization and cancer therapy can contribute to decreased food intake in
      children and adolescents with cancer, making it a challenge to meet their
      nutritional needs. The affect of hospitalization and the eating environment for
      pediatric oncology patients has not been studied very well, and the effect of
      altering the social aspect of mealtime for hospitalized pediatric oncology
      patients has not been studied at all. The authors conducted a randomized,
      prospective clinical trial to determine if hospitalized pediatric oncology
      patients consume more protein and calories when eating with a family member or
      when eating alone in their room at mealtime. All food and beverage intake was
      recorded for 3 consecutive days, and a food service satisfaction survey was
      completed on Day 3. Food records were analyzed for calorie and protein intake,
      and surveys were analyzed for patient/parent satisfaction. The study was
      completed by 200 hospitalized patients and their parent/caregiver. Overall,
      neither calorie nor protein intake differed significantly between the two groups,
      but patient/parent satisfaction was significantly higher in the group of patients
      who dined with their caregiver. By using analysis of variance, the authors found
      that ideal body weight and years of sickness were significantly associated with
      calorie and protein intake.

PMID- 15490868
TI  - Psychosocial adjustment of adolescent siblings of hematopoietic stem cell
      transplant patients.
AB  - Hematopoietic stem cell transplantation (HSCT) is a widely practiced therapy for
      many life-threatening childhood disorders. The authors investigated the
      psychosocial effects of HSCT on siblings of pediatric HSCT patients (n = 44; 21
      donors, 23 nondonors, ages 6 to 18 years). Donor siblings reported significantly
      more anxiety and lower self-esteem than did nondonors. Nondonors showed
      significantly more school problems. Approximately one third of all siblings
      reported moderate to severe posttraumatic stress. The study drew on the
      developmental theory of Erik Erikson and the psychosocial model of posttraumatic
      stress. As part of the study, the authors used the Measures of Psychosocial
      Development (MPD), a self-report measure based on Eriksonian constructs. The MPD
      was used to assess the psychosocial adjustment of 12 siblings who were
      adolescents (> or =13 years) at the time the study was conducted. In this
      article, findings are presented from the MPD as well as salient findings from the
      larger study.

PMID- 15490869
TI  - [Comparative genomic hybridization analysis of laryngeal carcinoma].
AB  - In order to find out the genes involved in the tumorigenesis of laryngeal
      carcinoma, we analyzed 18 laryngeal carcinoma with comparative genomic
      hybridization. Results show that each one has different degree of variances,
      included gains and losses of partial and whole chromosome. Each case has 12.9
      abnormal regions averagely; losses are more than gains, equal to 7.2 and 5.7 per
      case respectively. Main regions are gains in chromosomes 3q (78%), 5p (61%), 11q
      (56%), 1q (50%), 8p (44%), 8q (39%) and 15q (39%), and losses of 3p (70%), 5q
      (78%), 9p (67%), 13q (50%), 1p (44%) and 14q (39%). There are many specific gains
      and losses in several chromosomes,especially the increase of copy number
      karyotype in 1p13-21(8/18), 3p21-23 (14/18), 5p21-22 (14/18), 9p12-pter (10/18)
      and 13q21-31 (8/18), while the decrease in 1q11-21 (11/18), 3q15-21 (12/18), 8p22
      24 (6/18), 11q12-13 (8/18), 15q21-23 (7/18), 18p11 (8/18) are the characteristic
      varieties. These results suggest that there are oncogene, tumor suppressor gene
      and other associated genes involved in the tumorigenesis.

PMID- 15490870
TI  - [Molecular cloning and expression analysis of a novel human testis-specific
      gene].
AB  - Digital Differential Display (DDD) of the National Center for Biotechnology
      Information (NCBI) is a quantitative method that enables the user to determine
      the fold differences between the libraries being compaired, using a statistical
      method to quantitate the transcript levels. In this study, DDD program was
      performed between nine testis libraries ('tester') and seventy-six libraries
      derived from other tissues ('driver'). We identified a new contig of expression
      sequence tags (ESTs) HS. 129794 which were from testis libraries. To validate the
      use of bioinformatics approaches in gene discovery, the ESTs HS. 129794, which
      was predicted to be testis -specific, was chosen for further study. Reverse
      transcriptase polymerase chain reaction (RT-PCR) analysis of mRNA from different
      normal tissues indicated that HS. 129794 was specifically expressed in human
      testis. By querying EST and Unigene datagases, a full-length cDNA sequence of
      novel gene in human were identified, it was 2 430 bp in length, located in
      chromosome 3p21.1. The sequence of the open reading frame was 676 approximately 1
      248 bp, as was confirmed by RT-PCR and sequencing in human testis. The cDNA
      encodes a novel protein of 190 amino acids with a theoretical molecular weight of
      20 417.8 and isoelectric point of 5.23. The sequence shares no significant
      homology with any known protein in databases. Semi-quantitative RT-PCR analysis
      of multiple tissues further showed that the novel gene is expressed significantly
      in different stage of human testis and sperm. We hypothensize that its functions
      as a testis-specific and spermatogenesis related gene that plays some roles in
      spermatogenesis, and named it SRG5 (Testis Spermatogenesis Related Gene 5, SRG5)
      (GeneBank accession number: AY221117). Identification of SRG5 using DDD
      approaches validates gene discovery using computational approaches.

PMID- 15490871
TI  - Constitutive expression of human angiostatin in Pichia pastoris using the GAP
      promoter.
AB  - The GAP gene promoter was amplified from P. pastoris GS115 and used to replace
      the AOX1 promoter (P(AOX1)) on pPIC9K resulting in plasmid pGAP9K. The
      recombinant expression vector pGAP9K-AS was constructed by inserting the
      angiostatin gene(AS) into pGAP9K. pGAP9K-AS was then transformed into P. pastoris
      GS115. The multi-copy integration transformant P. pastoris GS115 (pGAP9K-AS) was
      used to investigate the constitutive expression of angiostatin in P. pastoris.
      The expression of angiostatin reached its peak after 4 d of culture in P.
      pastoris GS115 (pGAP9K-AS) while the angiostatin expressed in P. pastoris GS115
      (pPIC9K-AS) after 4 d of induction or 5 d of culture is only 70% of that
      expressed by P. pastoris GS115 (pGAP9K-AS). The AS expression in inducible system
      reached the peak after 6 d of induction but the expressed AS was only 86% of that
      from constitutive system. The results of anti-angiogenic and antitumor activity
      assay showed that AS expressed from both constitutive and inducible system
      inhibited the CAM angiogenesis and suppressed B16 melanoma in C57BL/6J mouse and
      that the tumor inhibition rates reached 90.63% and 90.54%, respectively. The
      above data indicates that the constitutive promoter P(GAP) can served as an
      effective alternative to the inductive promoter P(AOX1) to express AS and other
      proteins in P. pastoris.

PMID- 15490872
TI  - [Study on a human tissue-type plasminogen activator mutant cDNA knocked-in the
      beta-casein gene site of murine ES cells].
AB  - A murine beta-casein gene targeting vector was constructed using the cloned
      genomic sequence. The short arm was 2.7 kb including mouse beta-casein gene 5'
      flanking sequence, exon1, intron1 and partial exon2. The long arm is a 3.4 kb
      fragment including partial intron2, exon3 approximately 7, intron3 approximately
      6 and partial intron7. The human t-PA mutant cDNA was subcloned in the exon2 and
      fused with the mice beta-casein signal peptide sequence. The positive selective
      marker neo was placed in the middle of intron2. A tk negative selective marker
      was just outside the short arm. TC-1 ES cells were cultured and amplified on G418
      resistant feeder layer. The linearized targeting construct DNAs of 45 microg were
      introduced into 2 x 10(7) ES cells by electroporation. Totally 192 ES clones were
      picked up after cultured in G418 and Gancyclovir for 7 days. The colonies were
      amplified and subjected to genomic DNA preparation. The genomic DNAs were
      digested with EcoR I and used for Southern blot analysis. A probe inside the 5'
      homologous arm was used for hybridization. A 9.8 kb band was found in wild type,
      but the band was shift down from 9.8 kb to 6.6 kb in the beta-casein gene
      targeted allele because a new EcoR I site was introduced into the exon2 along
      with the human t-PA mutant gene. There were 9.8 kb and 6.6 kb bands in targeted
      ES cells. One clone of targeted ES cells with correct homologous recombination
      events was obtained among 78 analyzed clones. It lays foundation for gene
      targeted mice making.

PMID- 15490873
TI  - [Analysis of gene expression profiles in heart tissues from two breeds of pigs].
AB  - To study the expression profiles in the heart tissues of domestic pigs,five un
      normalized cDNA libraries from Danish adult female Landrace heart, biceps
      femoris, aorta, left ventricle tissues and Chinese adult female Erhualian heart
      tissue were constructed. Totally 35 180 expressed sequence tags (ESTs) were
      randomly sequenced. Using functional clustering and statistic methods, three gene
      clusters and 47 genes highly expressed in Landrace heart tissue were found. These
      genes are corresponding to the chaperone activity, motor activity and physiology
      process, implying the functional importance of the protection and movement
      process in heart. Between the two pig breeds, most of the differentially
      expressed genes are related with energy metabolism and catalytic activity, of
      which the majority are highly expressed in Landrace. The results indicate that
      the physiological activities of Landrace heart are more active and effective than
      Erhualian heart.

PMID- 15490874
TI  - [Transgenic mice produced by exchromosomal homologous recombination combined with
      cytoplasmic injection].
AB  - An expression construct specified in mammary gland with double cistrons of human
      G-CSF gene and IRES-EGFP gene under control of ovine beta-lactoglobulin gene
      flanking sequence, has been constructed in two parts (named fragment I and
      fragment II) that share an overlapping region of 2.2 kb sequence. Two sites of
      loxp and lox2272 for homologous recombination were inserted into both flanking
      regions of G-CSF. The lengths of fragment I and fragment II are 5.9 kb and 5.6
      kb, respectively. The whole length of the expression vector (beta-LG-hG-CSF-IRES
      EGFP) is 9.3 kb. The two DNA fragments mixed with nuclear locating sequence DNA
      (NLS) fragment were coinjected into murine zygote cytoplasm. The resulting mice
      were analyzed for the transgene integration and expression. A total of 138
      founders were born. 62.3% (86/138) of them was integrated with fragment I
      sequence, and 54.3% (75/138) of them contained fragment II, whereas 62 of them
      contained both fragment I and II, of whom 80. 6% (50/62) were integrated by the
      whole reconstituted gene construct (result of ex-chromosomal homologous
      recombination, ECR). By RT-PCR analysis, it was shown that 90% of the ECR mice
      (9/10) expressed human G-CSF gene and 100% expressed EGFP gene. EGFP expression
      was also detected by absorption spectrum scanning from 400 nm to 700 nm, and 50%
      (5/10) of the ECR mice expressed EGFP protein. The high frequency and accuracy of
      homologous recombination in murine zygotes reported here suggests that some large
      transgenes could be constructed by ECR pathway. This method does not need to
      construct a long complex DNA vector directly and to do nucleus-injection, and is
      easier than traditional method.

PMID- 15490875
TI  - [Comparison of different models for estimating genetic parameters of early growth
      traits in cashmere goat].
AB  - Using data on early growth traits (including birth weight, weaning weight, daily
      gain, and yearling weight) of cashmere goat from the Aerbasi White Cashmere Goat
      Breeding Farm in Inner Mongolia, four different animal models for estimating
      genetic parameters were compared. The four models differ in the way of handling
      maternal genetic effect and maternal environmental effect: in model I both
      maternal genetic and environmental effect were excluded, in model II only
      maternal genetic effect was included, in model III only maternal environmental
      effect was included, and in model IV both maternal genetic and environmental
      effect were included. The variance components under different models were
      estimated with derivative-free restricted maximum likelihood (DFREML) method
      using the MTDFREML program. The differences between different models were tested
      by likelihood ratio test. The results show that both maternal genetic and
      environmental effect have highly significant effect on birth weight. For weaning
      weight and daily gain the maternal genetic effect is not significant while the
      maternal environmental effect is highly significant; for yearling weight the
      maternal genetic effect is significant while the maternal environmental effect is
      not.

PMID- 15490876
TI  - [Polymorphism in intron 2 of crucian carp GH I gene].
AB  - High length and nucleotide polymorphisms in intron2 of GH I gene were detected in
      162 individuals,which were from seven wild crucian carp colonies, two goldfish
      colonies and one Fangzheng crucian carp colony. Using denaturating polyareylamide
      gel electrophoresis (DPAGE) and single-strand conformation polymorphism (SSCP),
      seven length variants and 15 haplotypes were identified in these fishes. The
      length types and haplotypes diversity was 4.32% and 9.26%, respectively. Sequence
      analysis of the 15 haplotypes indicated the following results: (1) The size of
      intron2 varied from 243 to 263 bp. In the 15 haplotypes,the average percentages
      of the four bases (A,T,G and C) were 34.13%, 37.36%, 15.13% and 13.38%,
      respectively; the frequency of G + C(28.51%) was much lower than that of A + T
      (71.49%). The GT/AG domain was found in exon-intron junctions,which was the 5'
      and 3' splice donor and acceptor sites in higher eukaryotic gene introns. The
      similarity sequence of GTAAGTA was located on the junction between exon2 and
      intron2. And there existed a richer pyrimidine region (TTTGCCTTTTGTTATC) near the
      3' end of intron2. (2) The seven length variants (A, B, C, D, E, F and G) were
      determined to be 189, 196, 204, 205, 206, 207 and 209 bp, respectively. The
      polymorphism resulted from the variable repeat number of T (N = 0, 8, 9, 10, 11
      and 13) and the difference in one or two motifs deletions of TGAAAAC, TT and
      GAGTG. (3) Compared the sequences of the 15 haplotypes, 17 substitution sites
      were observed, of which two were of transversion sites and 15 were of transition
      sites. Obviously, the transition mutations (88.24%) were more frequent than
      transversion mutations (11.76%). Analysis of the distributions of the length
      types, haplotypes and composite genotypes suggested that genetic diversity was
      varied in different colonies. In the goldfish colonies, only one length type (A),
      two haplotypes (A1 and A2) and one composite genotype (A1A2) were observed. Two
      length types (C and D), four haplotypes (C1, C2, D2 and D5) and one composite
      genotype (C1C2D2D5) presented in the Fangzheng crucian carp colonies. The highest
      level of genetic diversity was exhibited in the seven wild crucian carp colonies:
      seven length types (A, B, C, D, E, F and G), 14 haplotypes (A1, A2, A3, B, C1,
      C2, D1, D2, D3, D4, E1, E2, F and G) and 14 composite genotypes (A1A2A3, A1A2A3B,
      A1C1C2D1D2D3, A1C1C2D2, A1C1C2D2D3, A1C1C2D3E2, BC1C2D2, BC1C2D3D4, C1C2D2,
      C1C2D2D3, C1C2D3D4, C1C2D3D4F, C1C2D4, D2E1G) were shared by the seven wild
      colonies. The numbers of observed length types, haplotypes and genotypes within
      the wild colonies ranged from 3 to 6, 6 to 10 and 2 to 6, respectively. Whether
      the length and nucleotide polymorphisms in the intron2 of crucian carp GH I gene
      were associated with gene expression and gene regulation remained unsolved and
      required further investigations.

PMID- 15490877
TI  - [Conservation efficiency of local chicken breeds in different farms as revealed
      by microsatellite markers].
AB  - Twenty-eight microsatellite markers were used to analyze the conservation
      efficiency of two local chicken breeds (Dagu Chicken and Beijing Fatty Chicken)
      in different farms. Genotypes were detected in 125 samples. The genetic
      variations among and within the populations were calculated by the number of
      alleles, gene frequency, genetic heterozygosity (H), PIC, F-statistics, Nei's
      genetic distance and UPGMA. High polymorphism was found in the four populations,
      and H and PIC values of each population were more than 0. 5. All loci detected in
      the study showed polymorphism and the number of alleles ranged from 2 to 22 in
      total population. Most of these loci were at Hardy-Weinberg equilibrium except
      two loci (LE110194, MCW0032). The four conservation farms for the two breeds were
      shown to have retained substantial biodiversity, indicating that the conservation
      programs are efficient. However, differences between the farms of the same breeds
      were observed.

PMID- 15490878
TI  - Identification of chromosome regions associated with seedling vigor in rice.
AB  - Seedling vigor is important for optimum stand establishment in rice cropping. In
      this paper,a set of 264 F12 recombinant inbred lines (RILs) derived by single
      seed descent from a cross between Lemont (japonica) and Teqing (indica) was
      phenotyped for three seedling vigor related traits, including seed germination
      rate (GR), seedling shoot length and dry weight by the rolled paper towel tests.
      The phenotype data and a linkage map consisting of 198 DNA markers were combined
      to map quantitative trait loci (QTL) for seedling vigor by using a computer
      program QTLMapper1.0. A total of 13 putative main-effect QTL were detected. All
      of these QTL had much smaller effects on the traits with a mean R2 of 6.2%,
      ranging from 2.9% to 12.7%. As for digenic interaction, 18 pairs of epistatic
      loci with R2 > or = 5% were resolved with a mean R2 of 6.9% ,ranging from 5.1% to
      11.8%, which was slightly larger than that of the main-effect QTL identified for
      the traits. The majority of the main-effect and epistatic loci detected for
      seedling vigor related traits were clustered in a few chromosome regions.
      Together, seven such chromosome regions (CRs), each with three or more seedling
      vigor main-effect and epistatic loci, were found to be highly associated with
      seedling vigor. These CRs can be classified into three types, i.e. M-CRs, E-CRs
      and ME-CRs. For some CRs just like CR(SV-6), the QTL within one CR were found to
      interact simultaneously with QTL within more than one other CRs to affect
      different seedling vigor related traits. The above results revealed that seedling
      vigor in rice is controlled by many loci, most of which have relatively small
      effects. Comparatively, epistasis as a genetic factor would be more important
      than main-effects of QTL for seedling vigor in rice. Nevertheless, the effects of
      the QTL are still large enough to be detected and in fact several chromosome
      regions were found to be highly associated with seedling vigor in very different
      populations as compared with previous studies. Molecular tagging of favorable
      alleles and marker-aided selection strategy may, therefore, be a promising
      approach to the improvement of rice seedling vigor.

PMID- 15490879
TI  - [Identification and analysis of F2 stable population derived from the cross of
      triploid x diploid in rice].
AB  - Polyploid strain 149-B, that was generated naturally from a rice twin-seedling
      population SAR-2, has been determined as triploid (2n = 36). It was then used as
      the female parent crossing with a normal diploid variety SH R363. From its F2
      generation we obtained a genetic-stable population. To prove the uniformity of
      such a population, SSR markers were used to survey the F2 individual plants. The
      results showed that F2 individuals carried only one parental molecular marker at
      each polymorphic locus, and their genotypes were identical with F1 progeny. Based
      on the above experiments, we consider that this F2 population is definitely an
      early-generation stable population. Meanwhile, we discussed the possible
      mechanism of the special phenomenon as well.

PMID- 15490880
TI  - [Relationship between genetic lineage and pathotype of Pyricularia grisea in
      Yunnan Plateau].
AB  - Rice blast caused by Pyricularia grisea is the most destructive disease in Yunnan
      Plateau, China. In order to elucidate the relationship between genetic lineage
      and pathotype of P. grisea of Yunnan Plateau as well as the variability of the
      fungus at DNA level,the repetitive element-based PCR (rep-PCR) of Pot2, an
      element found in approximately 100 copies in the fungus genome,was exploited. Two
      hundred and thirty-six isolates of P. grisea collected from 15 main rice-growing
      counties of Yunnan Plateau were fingerprinted by using rep-PCR. A linkage graph
      of the rep-PCR fingerprints from 134 representative isolates was generated using
      an unweighted pair-grouped average program (UPGMA) of the STATISTICAL 5.0
      software. The isolates were classified into 8 genetic lineages (G1 approximately
      G8) at the level of 1.75 genetic linkage distance, of which the G1, G2 and G4
      were the dominant lineages. The isolates in a certain area generally belonged to
      one correspondent genetic lineage and the isolates from the same plot and host
      rice variety mostly shared one linkage group though different genetic lineages
      within one lesion. Furthermore, 29 isolates representing the eight genetic
      lineages were inoculated on 33 rice cultivars of Yunnan at the stage of 3
      approximately 4 leaves in greenhouse. The isolates were divided into 6 pathotype
      groups (P1 approximately P6) according to its compatibility, which demonstrated
      that some isolates of one genetic lineage sharing two or three pathotype groups,
      alternatively, one or four pathotype groups. The isolates from each genetic
      lineage, however, may share one pathotype group such as P2. The preliminary
      results implicated that the relationship between genetic lineages and pathotype
      groups of P. grisea in Yunnan Plateau was complicated rather than simple. On the
      other hand,2 rice cultivars including HeXi 16 and JingGuo 92 were resistant to
      the 29 isolates but YunJing 20 and HeXi 30 both susceptible to all of them, which
      was helpful for deploying the blast-resistant genes in rice production of Yunnan
      Plateau. Therefore, the rice blast-resistance spectrum of the tentative new rice
      cultivars should be evaluated before its release considering the blast-resistant
      rice breeding and the practice of rice production in Yunnan Plateau.

PMID- 15490881
TI  - Cloning and expression analysis of a bZIP cDNA in Gossypium hirsutum L.
AB  - A new full-length cDNA clone was isolated from the fiber cDNA library of
      Gossypium hirsutum L. The cDNA, designated GhbZIP,encoded a polypeptide of 645
      amino acids. GhbZIP protein had the structure characteristics of plant bZIP
      proteins, including two conserved domains, DUF630 and DUF632 with unknown
      functions, a proline-rich domain and a phenylalanine-rich domain. Meanwhile, the
      protein contained a leucine zipper-like motif in DUF632. The hydropathy analysis
      showed that the GhbZIP was a membrane protein. GhbZIP gene was preferentially
      expressed in ovule and fiber cells since three days post-anthesis, as indicated
      it might be involved in the transcription regulation of genes during cotton fiber
      elongation.

PMID- 15490882
TI  - [Evaluation of application of a new molecular marker SRAP on analysis of F2
      segregation population and genetic diversity in cotton].
AB  - SRAP (Sequence-related Amplified Polymorphism), a new marker system, was applied
      in cotton genome analysis. We developed an efficient PCR reaction system for
      detecting SRAP that showed reliable, effective and reproductive. SRAP marker was
      used to detect the polymorphisms between 'Pima90' (G. barbodense) and '
      Handan208' (G. hirsutum) and showed comparatively high polymorphism. Among the 30
      primer pairs, 29 pairs generated 149 polymorphic bands with an average of 5.14
      polymorphic bands per primer pair. The primer pair showing most polymorphism was
      the combination of me3 and em2, which produced 13 polymorphic bands. The SRAP
      marker was also tested among 11 upland cotton cultivars, 15 of the tested 30
      primer pairs showed polymorphism yielding 22 polymorphic genetic loci, which is
      relatively high among upland cotton cultivars. The results showed that SRAP
      marker could be widely used in molecular genetic map construction and germplasm
      evaluation of cotton.

PMID- 15490883
TI  - [Bioinformatics studies on photosynthetic system genes in cyanobacteria and
      chloroplasts].
AB  - This study compared homology of base sequences in genes encoding photosynthetic
      system proteins of cyanobacteria (Synechocystics sp. PCC6803, Nostoc sp. PCC7120)
      with these of chloroplasts (from Marchantia Polymorpha, Nicotiana tobacum, Oryza
      sativ, Euglena gracilis, Pinus thunbergii, Zea mays, Odentella sinesis,
      Cyanophora paradoxa, Porphyra purpurea and Arabidopsis thaliana) by BLAST method.
      While the gene sequence of Synechocystics sp. PCC6803 was considered as the
      criterion (100%) the homology of others were compared with it. Among the genes
      for photosystem I, psaC homology was the highest (90.14%) and the lowest was psaJ
      (52.24%). The highest ones were psbD (83.71%) for photosystem II, atpB (79.58%)
      for ATP synthase and petB (81.66%) for cytochrome b6/f complex. The lowest ones
      were psbN (49.70%) for photosystem II, atpF (26.69%) for ATP synthase and petA
      (55.27%) for cytochrome b6/f complex. Also, this paper discussed why the homology
      of gene sequences was the highest or the lowest. No report has been published and
      this bioinformatics research may provide some evidences for the origin and
      evolution of chloroplasts.

PMID- 15490884
TI  - [Genetic variation analysis of SARS coronavirus].
AB  - Severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) has
      been verified as the causative agent of a worldwide outbreak of SARS. Since the
      observed per-base replication error-rate of RNA polymerase is about 3 x 10(-5),
      RNA virus populations typically contain genetic variants that form a
      heterogeneous virus pool. This feature confers great adaptability on viruses and
      is partly responsible for current difficulties of viral disease prevention and
      control, such as of HIV and HCV infections. SARS-CoV, a newly-identified single
      strand RNA virus, has been identified with common variable property of RNA
      viruses. In this study, genetic variation of SARS-CoV is analyzed based on
      available documented data and our study. It suggests that SARS-CoV is of similar
      mutation frequency and dynamic mutant distributions like other RNA viruses,
      though relatively less identified variation number than those causing chronic
      infections. In contrast, the viral spike (S) gene exhibits high variation, while
      nucleocapsid (N) gene shows relative sequence conservation. No obvious
      correlation is observed between viral variation and clinical disease
      manifestation from present analyzed data.

PMID- 15490885
TI  - [Nuclear reprogramming of somatic nuclear transfer embryos].
AB  - Although the cloned animals have been successfully generated in a number of
      mammalian species, there are still many problems about this technology. The
      developmental aberrancies include a high rate of abortion during early gestation
      and high rate of perinatal death. The main cause of these problems may be
      attributed to the epigenetic reprogramming of somatic donor genome. During
      mammalian embryonic development, DNA methylation is an essential process in the
      regulation of transcription. There are many aberrant methylation in various
      genomic regions of cloned embryos. The gene imprinting of cloned embryos are also
      abnormal.

PMID- 15490886
TI  - IQ-discrepancy definitions and the diagnosis of LD: introduction to the special
      issue.

PMID- 15490887
TI  - Gender bias in IQ-discrepancy and post-discrepancy definitions of reading
      disability.
AB  - The present study investigated the hypothesis that the higher prevalence of
      reading disability (RD) often observed among boys is partly an artifact of gender
      bias in the prediction of reading from IQ. The relevant regression statistics
      derived from a sample of more than 900 children revealed a statistically
      significant intercept bias. Predicted reading scores for boys were systematically
      overestimated, thereby inflating IQ-reading discrepancies; the converse was found
      for girls. When defined separately for girls and boys, severe underachievement in
      reading was found to be equally prevalent in both genders and, furthermore, was
      associated with qualitatively and quantitatively similar patterns of deficits.
      Because the bias arose from general differences between boys and girls in reading
      score distributions (a lower mean and greater variance for boys) rather than from
      differences in IQ scores, gender bias poses a potential threat not only to
      traditional IQ-discrepancy definitions but also to post-discrepancy definitions
      that are based solely on reading score cutoffs. Future classification criteria
      for RD need to take heed of the possibility that when the distributions of
      reading scores for boys and girls are not identical, performance cutoffs
      designating low achievement that are based on data pooled from both genders are
      likely to result in the overidentification of boys with RD and the
      underidentification of girls with RD.

PMID- 15490888
TI  - The relationship between IQ and reading disabilities in English-speaking Canadian
      and Spanish children.
AB  - This study was designed to examine the role of intelligence (IQ) in the
      definition of reading disabilities (RD) in languages with different orthographic
      systems. A sample of 94 Spanish children and 157 English-speaking Canadian
      children with RD was classified into four groups on the basis of IQ scores from
      the Wechsler Intelligence Scale for Children-Revised (< 80; 81-90; 91-109; 110
      140). We examined the reading and spelling skills of Canadian and Spanish
      children as a function of Full Scale, Verbal, and Performance IQ scores.
      Significant differences between the languages were found when reading performance
      was analyzed as a function of Verbal IQ scores, in that there were some
      differences between the groups of Canadian children with RD but not between the
      groups of Spanish children. The Canadian children with Verbal IQ scores < 80
      demonstrated relatively lower performance in reading and spelling skills than the
      Canadian groups with higher IQ scores. There were differences in reading tasks as
      a function of Performance IQ in English but not in Spanish. The differences in
      the role of IQ as a function of orthographic systems may relate to the greater
      significance of visual-orthographic as opposed to phonological processing in
      English.

PMID- 15490889
TI  - Predicting response to early reading intervention from verbal IQ, reading-related
      language abilities, attention ratings, and verbal IQ-word reading discrepancy:
      failure to validate discrepancy method.
AB  - Additional analyses of a previously published study addressed three questions
      about growth in word reading during early reading intervention: (1) How well do
      Verbal IQ, reading-related language abilities (phonological, rapid naming, and
      orthographic), and attention ratings predict reading growth? (2) How well do
      language deficits predict reading growth? and (3) How well does Verbal IQ-word
      reading discrepancy predict reading growth? Univariate analyses showed that
      Verbal IQ, phonological skills, orthographic skills, rapid automatized naming
      (RAN), and attention ratings predicted the response to early intervention, but
      multivariate analyses based on a combination of predictors for real-word reading
      and pseudoword reading showed that Verbal IQ was not the best unique predictor.
      Students with double or triple deficits in language skills (RAN, phonological,
      and orthographic processing) responded more slowly to early intervention than
      students without language deficits. Verbal IQ-word reading discrepancy did not
      predict the response to early intervention in reading. Overall results supported
      the use of reading-related language and attention measures rather than IQ
      achievement discrepancy in identifying candidates for early reading intervention.

PMID- 15490890
TI  - Do the effects of computer-assisted practice differ for children with reading
      disabilities with and without IQ-achievement discrepancy?
AB  - This study was designed to assess whether the effects of computer-assisted
      practice on visual word recognition differed for children with reading
      disabilities (RD) with or without aptitude-achievement discrepancy. A sample of
      73 Spanish children with low reading performance was selected using the
      discrepancy method, based on a standard score comparison (i.e., the difference
      between IQ and achievement standard scores). The sample was classified into three
      groups: (1) a group of 14 children with dyslexia (age M = 103.85 months; SD =
      8.45) who received computer-based reading practice; (2) a group of 31 "garden
      variety" (GV) poor readers (age M = 107.06 months; SD = 6.75) who received the
      same type of instruction; and (3) a group of 28 children with low reading
      performance (age M = 103.33 months; SD = 9.04) who did not receive computer
      assisted practice. Children were pre- and posttested in word recognition, reading
      comprehension, phonological awareness, and visual and phonological tasks. The
      results indicated that both computer-assisted intervention groups showed improved
      word recognition compared to the control group. Nevertheless, children with
      dyslexia had more difficulties than GV poor readers during computer-based word
      reading under conditions that required extensive phonological computation,
      because their performance was more affected by low-frequency words and long
      words. In conclusion, we did not find empirical evidence in favor of the IQ
      achievement discrepancy definition of reading disability, because IQ did not
      differentially predict treatment outcomes.

PMID- 15490892
TI  - The role of environment in the development of reading skills: a longitudinal
      study of preschool and school-age measures.
AB  - The purpose of this study was to extend previous studies on the influence of
      environmental measures on intelligence scores by examining how proximal and
      distal measures of children's environments in the preschool period and in the
      primary-grade period are related to their performance on reading achievement
      tests. Reading performance was explored using two approaches. The first approach
      involved the identification of children within a longitudinal sample who had poor
      reading skills at 8 years of age. The second approach used the full range of
      reading scores to explore whether factors influencing poor reading were different
      from those influencing good reading. Participants were 113 children, including 35
      children with poor reading skills, who were part of a longitudinal study of
      cognitive development. Socioeconomic status (SES), Home Observation for
      Measurement of the Environment (HOME) scores at 3 and 10 years of age, and school
      administered and individually administered reading achievement scores were
      obtained. Both SES and HOME scores were found to be related to reading abilities,
      but preschool environment measures were more strongly and consistently related to
      and predictive of reading scores. Differences in the patterns of correlations and
      the results of the predictive models were found between the full sample and the
      poor readers. Variables other than proximal and distal measures of the
      environment are involved in the development of reading skills.

PMID- 15490891
TI  - Cognitive functioning as measured by the WISC-R: do children with learning
      disabilities have distinctive patterns of performance?
AB  - Patterns of performance on the Wechsler Intelligence Scale for Children-Revised
      (WISC-R) have been proposed as useful tools for the identification of children
      with learning disabilities (LD). However, most of the studies of WISC-R patterns
      in children with LD have been plagued by the lack of a typically achieving
      comparison group, by failure to measure individual patterns, and by the lack of a
      precise definition of LD. In an attempt to address these flaws and to assess the
      presence of patterns of performance on the WISC-R, we examined data from 121
      children with typical achievement (TA), 143 children with reading disabilities
      (RD), and 100 children with a specific arithmetic disability (AD), ages 6 to 16
      years. The results indicated that the RD and AD groups had significantly lower
      scores than the TA group on all the Verbal IQ subtests. Many of the children with
      AD and RD showed a significant difference between Verbal and Performance IQ
      scores, but so did many of the typically achieving children. Although there were
      some children with LD who showed the predicted patterns, typically, 65% or more
      of the children with LD did not. Furthermore, a proportion of the TA group
      generally not significantly smaller than that of the RD and AD groups-showed
      discrepancy patterns as well. Our results indicate that the patterns of
      performance on intelligence tests are not reliable enough for the diagnosis of LD
      in individual children. Therefore, it might be more profitable to base the
      detection of an individual's LD on patterns of achievement test scores.

PMID- 15490893
TI  - Impaired visual attention in children with dyslexia.
AB  - Reading involves the correct and rapid identification of visual stimuli with
      letters and words. The processing of visual stimuli depends not only on the
      integrity of the peripheral and central visual system but also on the attentional
      systems involved. In the present study, a cue-target visual attention task was
      administered to a population-based sample of 25 children with dyslexia from 10 to
      12 years of age. A control group matched for group size, age, and gender was
      obtained from the same general population. A two-stage screening process involved
      a spelling task of regular words followed by a battery of five single-word
      reading tasks. The cue-target task involved both a computer-controlled stimulus
      presentation and a computer-controlled measurement of reaction time. The data
      were analyzed by visual field, cue condition (valid, invalid, and no cue), and
      cue-target interval (CTI). The results showed a general pattern of slower
      responses in the dyslexia group compared to the control group. The dyslexia group
      also had longer reaction times in the short CTI condition (covert shift of
      attention) and in the long CTI condition (overt shift of attention). The findings
      may reflect a general attentional deficit to visual stimuli in dyslexia, possibly
      related to problems with the recruitment of necessary cognitive resources for the
      performance of complex reaction time tasks and for fluent reading.

PMID- 15490894
TI  - The play and language behavior of mothers with and without dyslexia and its
      association to their toddlers' language development.
AB  - The play and language behavior of mothers with (n = 49) and without (n = 49)
      specific reading disabilities (RD) was investigated during play with their 14
      month-old children. The contribution of maternal behavior to the language
      development of their children was examined. The children's receptive and
      expressive language skills were assessed longitudinally at 14, 18, and 30 months,
      using the MacArthur Communicative Development Inventories and the Reynell
      Developmental Language Scales. Children with and without familial risk for RD did
      not differ from each other in any play or language measures at these ages. No
      group differences were found for mothers' manifestations of nonsymbolic play and
      language. However, the typically reading (TR) mothers produced significantly more
      symbolic play and language in play interactions with their child than did the
      mothers with RD. The correspondence between mother-child symbolic play and
      maternal play-related language was also higher for the TR group than it was for
      the RD group. The mothers' symbolic play did not show any relation to their
      children's language development, but their expressions of symbolic language did
      show a relationship. The mothers' child-directed symbolic language contributed
      significantly toward the comprehension skills of 14- and 18-month-olds in the RD
      group. This association, however, was lower at 30 months, at which point it was
      reliably present for the first time in the TR group.

PMID- 15490895
TI  - Clinical importance of parent ratings of everyday cognitive abilities in children
      with learning and attention problems.
AB  - This study addressed two issues: first, whether parental reports contribute
      information over and above a standardized psychometric assessment, and second,
      whether parental reports of everyday cognitive functioning might be useful in
      distinguishing between children with reading disabilities (RD), attention
      deficit/hyperactivity disorder (ADHD), and combined ADHD + RD. Parent-reported
      information on 159 children with learning or attention problems was obtained
      using a questionnaire called the Parent Ratings of Everyday Cognitive and
      Academic Abilities (PRECAA). Psychometric information used for comparison
      included the Woodcock-Johnson Psychoeducational Battery-Revised, the Bruininks
      Oseretsky Test of Motor Proficiency-Short Form, the Vocabulary and Block Design
      subtests of the Wechsler Intelligence Scale for Children, 3rd edition, and the
      Developmental Test of Visual-Motor Integration. The PRECAA was found to be
      sensitive to group differences between children with RD and children with ADHD
      and combined ADHD + RD. Its inclusion resulted in a significant increase in the
      number of children correctly classified compared to the use of psychometric
      measures alone. The PRECAA correctly classified more children (66%) than did the
      standard psychometric measures (50%). In fact, a very high percentage of children
      with ADHD (81%) were correctly classified using the PRECAA. These findings
      suggest that the PRECAA may be a useful aid to clinicians in the identification
      of children with learning and attention problems.

PMID- 15490896
TI  - The language of written language: an introduction to the special issue.
AB  - This special issue includes five articles dealing with selected aspects of
      writing disorders, crafted by key contributors to the literature on written
      language. Articles addressing definitional issues and diagnostic questions,
      assessment strategies, selected neurodevelopmental components of written
      expression, the manifestation of writing problems in children and young adults,
      direct intervention, training for elementary teachers in the early grades in the
      area of literacy, and brain-behavior linkages are presented. This introduction
      provides an overview of these articles tied to specific issues confronting the
      field of written language. Some thoughts and directions for the future are
      articulated.

PMID- 15490897
TI  - School is fun at recess: informal analyses of written language for students with
      learning disabilities.
AB  - The purpose of an informal analysis of written language is to identify what
      writers can do as well as what they find difficult about writing. This article
      reviews the varied components of written language, suggests informal means for
      assessment, and summarizes the cognitive and linguistic factors that influence
      varied aspects of writing performance. Two informal evaluation scales are
      presented that stress the interconnection between oral and written language
      processes.

PMID- 15490898
TI  - Discourse complexity of college writers with and without disabilities: a
      multidimensional analysis.
AB  - The purpose of this study was to examine specific word- and sentence-level
      features most frequently used in the expository writing of four groups of college
      writers. Three groups were writers who demonstrated disabilities. Group 1
      students (n = 87) demonstrated learning disabilities (LD); Group 2 (n = 50),
      attention-deficit/hyperactivity disorder (ADHD); and Group 3 (n = 58), combined
      LD and ADHD. Group 4 consisted of writers with no history of a documented
      disability (n = 92). Computer-based analysis and structural equation modeling
      were used to group specific linguistic features identified in the expository
      essays across all four groups. The frequency of linguistic features, not errors,
      was analyzed. Four communication dimensions (factors) were identified for the
      four groups of writers, but the factor loadings and correlations were
      significantly different across groups. Furthermore, the relationships of specific
      linguistic features were studied as to their impact on the verbosity, quality,
      and lexical complexity of students' expository essays. It is interesting to note
      that very high correlations were found between verbosity, quality, and lexical
      complexity, suggesting that these constructs are not as separate in their
      functioning as might be supposed. Implications for assessment and instruction are
      provided.

PMID- 15490899
TI  - Writing and reading: connections between language by hand and language by eye.
AB  - Four approaches to the investigation of connections between language by hand and
      language by eye are described and illustrated with studies from a decade-long
      research program. In the first approach, multigroup structural equation modeling
      is applied to reading and writing measures given to typically developing writers
      to examine unidirectional and bidirectional relationships between specific
      components of the reading and writing systems. In the second approach, structural
      equation modeling is applied to a multivariate set of language measures given to
      children and adults with reading and writing disabilities to examine how the same
      set of language processes is orchestrated differently to accomplish specific
      reading or writing goals, and correlations between factors are evaluated to
      examine the level at which the language-by-hand system and the language-by-eye
      system communicate most easily. In the third approach, mode of instruction and
      mode of response are systematically varied in evaluating effectiveness of
      treating reading disability with and without a writing component. In the fourth
      approach, functional brain imaging is used to investigate residual spelling
      problems in students whose problems with word decoding have been remediated. The
      four approaches support a model in which language by hand and language by eye are
      separate systems that interact in predictable ways.

PMID- 15490900
TI  - Executive functions in elementary school children with and without problems in
      written expression.
AB  - This study examined the executive functioning of 55 elementary school children
      with and without problems in written expression. Two groups reflecting children
      with and without significant writing problems were defined by an average primary
      trait rating across two separate narratives. The groups did not differ in terms
      of chronological age, ethnicity, gender, socioeconomic status, special education
      status, or presence of attention problems or receptive vocabulary capabilities;
      however, they did differ in reading decoding ability, and this variable was
      controlled for in all analyses. Dependent measures included tasks tapping an
      array of executive functions grouped conceptually in accordance with a model of
      executive functioning reflecting the following domains: initiate, sustain, set
      shifting, and inhibition/stopping. Analysis of covariance (ANCOVA) procedures
      revealed statistically significant group differences on the initiation and set
      shift domains, with the sustaining domain approaching significance. Children with
      writing problems performed more poorly in each of these domains, although the
      effect sizes were small. A multiple regression that employed these four factors
      and the reading decoding variable to predict the primary trait score from the
      written narratives revealed a statistically significant regression function;
      however, reading decoding contributed most of the unique variance to the writing
      outcome. These findings point out the importance of executive functions in the
      written language process for elementary school students, but highlight the need
      to examine other variables when studying elementary school-age children with
      written expression problems.

PMID- 15490901
TI  - Beginning literacy: links among teacher knowledge, teacher practice, and student
      learning.
AB  - Although the importance of phonological awareness has been discussed widely in
      the research literature, the concept is not well understood by many classroom
      teachers. In the study described here, we worked with groups of kindergarten and
      first-grade teachers (the experimental group) during a 2-week summer institute
      and throughout the school year. We shared with them research about learning
      disabilities and effective instruction, stressing the importance of explicit
      instruction in phonological and orthographic awareness. We followed the
      experimental group and a control group into their classrooms for a year,
      assessing teachers' classroom practices and their students' (n = 779) learning.
      The study yielded three major findings: We can deepen teachers' own knowledge of
      the role of phonological and orthographic information in literacy instruction;
      teachers can use that knowledge to change classroom practice; and changes in
      teacher knowledge and classroom practice can improve student learning.

PMID- 15490902
TI  - The socioemotional adjustment of adolescents with LD in the kibbutz during high
      school transition periods.
AB  - This study examined several aspects of the socioemotional experiences (i.e.,
      loneliness, social skills, reciprocal friendship, reciprocal rejection, and
      social status) of adolescents with and without learning disabilities in an
      Israeli kibbutz environment during school transition periods. The sample
      consisted of 106 students with learning disabilities (LD; 74 boys and 32 girls)
      and 101 students without learning disabilities (NLD; 62 boys and 39 girls) drawn
      from seventh grade (i.e., early adolescence) and ninth grade (i.e., middle
      adolescence). The results revealed that seventh- and ninth-grade adolescents with
      LD received more social peer rejection than did NLD group adolescents, and
      students with LD were judged by their teachers to exhibit lower social skills and
      higher behavioral problems than their classmates. No significant group
      differences were found on loneliness, but an age-related increase in loneliness
      feelings was noted, which was independent from group membership and gender.
      Gender differences on self-report, peer ratings, and teachers' ratings on social
      measures in favor of girls were demonstrated. The discussion focuses on the
      potential impact of school transitions and of the developmental environment
      provided in the kibbutz on adolescents' socioemotional functioning and
      adjustment.

PMID- 15490903
TI  - A rapid screening measure for the identification of visuospatial learning
      disability in schools.
AB  - Verbal and nonverbal forms of developmental learning disabilities have been
      reported. Whereas there are several instruments for evaluating children for the
      presence of verbal learning disabilities at school, no screening tool is
      available to identify children who have nonverbal learning disabilities. This
      study aimed at devising and validating a short screening questionnaire that can
      be used by teachers in primary schools to identify those children who need to be
      referred for clinical services because they have a visuospatial learning
      disability (VSLD). An 18-item Shortened Visuospatial Questionnaire (SVS) was
      derived from an earlier, longer version. Its validation procedure was twofold and
      was achieved by (a) verifying that children who had been identified with the SVS
      questionnaire as having a VSLD actually showed visuospatial deficits on
      psychometric evaluation and by (b) rating with the SVS a clinically identified
      population of children with VSLD. The results of the validation procedure showed
      that the SVS is a quick, reliable, and valid instrument that may be helpful in
      identifying children with VSLD in primary school.

PMID- 15490904
TI  - Dyslexia and dysgraphia: more than written language difficulties in common.
AB  - A dual-task paradigm involving concurrent finger tapping and line orientation
      judgment was used to investigate brain processing differences in early adolescent
      good readers/poor spellers (dysgraphia), poor readers/poor spellers (dyslexia)
      and good readers/good spellers. Whereas all groups were similarly affected during
      the left-hand tapping condition, in the right-hand tapping condition the good
      spelling group displayed significantly less tapping disruption than both poor
      spelling groups, who did not differ significantly from each other. From these
      results, it can be inferred that individuals with dyslexia and dysgraphia share a
      left-hemisphere processing limitation that is not confined to written language.
      In light of other relevant research findings, I suggest that this limitation is
      due to the absence of a disembedding scanning mechanism for converting spatial
      arrays (e.g., spelling patterns) to temporal form-an impairment putatively caused
      by attempting to teach written language to children who are late in establishing
      left-hemisphere motor dominance.

PMID- 15490905
TI  - Children at risk for learning disorders: multiple perspectives.
AB  - This study examined the contribution of a multidimensional model of risk factors
      in explaining adaptive functioning among 5- to 6.5-year-old kindergartners with
      mild developmental delays who were considered at risk for developing learning
      disorders. Risk factors included (a) child characteristics, (b) maternal and
      familial ecological variables, and (c) the child's attachment style as perceived
      by the mother. The sample included 145 Israeli mother-child dyads: 70 mothers and
      their children at risk for developing learning disorders (51 boys, 19 girls) and
      75 mothers and their typically developing children (46 boys, 29 girls) from the
      same general education kindergartens. Data were collected from children's self
      reports, mothers' narratives, and teachers' ratings. Path analysis examined the
      multidimensional risk model for the two groups. The study indicated a high fit
      between the theoretical model and the empirical findings and showed a different
      pattern of relations between the model's components for the two populations
      studied.

PMID- 15490906
TI  - Learning disabilities and bullying: double jeopardy.
AB  - Independently, learning disabilities (LD) and involvement in bullying each pose a
      risk for social, emotional, and behavioral problems. Based on the research to
      date and on the characteristics common to children with LD and children who are
      bullied, there is reason to believe that children with LD are at increased risk
      of victimization. However, there is little research on the relationship between
      LD and bullying. This article presents factors and characteristics that make
      children and youth with LD vulnerable to bullying. Risk factors and effects of
      bullying are reviewed. Implications for practice and research are discussed.

PMID- 15490907
TI  - Students classified as LD who petitioned for or fulfilled the college foreign
      language requirement-are they different? A replication study.
AB  - This replication study compared 86 petition students who received course
      substitutions for the college foreign language (FL) requirement with 40
      nonpetition students who fulfilled the FL requirement by passing FL courses on
      cognitive and academic achievement measures and graduating grade point average.
      The results showed significant differences between the two groups, favoring the
      nonpetition group on one measure, the American College Testing (ACT) score, when
      IQ was used as a covariate; however, no significant group differences remained
      when ACT score was used as a covariate. More than half of the 126 petition and
      nonpetition students did not meet a minimum criterion for classification as
      learning disabled (LD), and more than half of both groups (54% and 63%,
      respectively) were not classified as LD before enrolling in college. Sixty
      percent of the petition students either had not taken an FL course in college or
      had achieved only grades of withdrawal before petitioning for substitution of the
      FL requirement. Implications addressed include petition students' persistence in
      fulfilling the FL requirement, students' use of instructional accommodations and
      services, criteria used to classify students as LD, use of the Modern Language
      Aptitude Test (MLAT), and why some students classified as LD pass FL courses and
      other students classified as LD do not.

PMID- 15490908
TI  - Dyslexia and the life course.
AB  - The life stories of adults diagnosed with dyslexia as children were examined,
      with emphasis on the related emotional experiences. The life story method of
      narrative analysis was used to compare and analyze the accounts of 12
      participants who were interviewed extensively. The findings indicated that self
      esteem problems may emerge by early childhood as individuals contend with aspects
      of their learning disabilities that interfere with typical development. By school
      age, all participants noted self-esteem problems when they experienced struggles
      or failures in school, which could feel traumatic. Testing and diagnosis improved
      self-esteem when conducted in a relevant manner that led to adaptation. The
      central plots of the participants' lives were characterized by the interplay
      between the functional challenges of their learning disabilities and the related
      self-esteem issues. Compensation involved the individual's areas of competence
      and the resources within the environment. Niches in late adolescence and young
      adulthood held potential to dramatically improve compensation. Participants
      generally exhibited four ways of life in adulthood and an added sense of
      emotional insecurity. Each attempted to integrate lifelong emotional experiences
      related to living with diagnosed dyslexia.

PMID- 15490909
TI  - The internal restlessness scale: performance of college students with and without
      ADHD.
AB  - Attention-deficit/hyperactivity disorder (ADHD) was previously believed to be a
      disorder of childhood, with symptoms attenuating at the onset of puberty. Follow
      up studies, however, suggest that the majority of children with ADHD continue to
      manifest symptoms into adulthood. Although the inattention components associated
      with ADHD persist into adulthood, the nature of the hyperactivity component is
      less well understood. For example, according to criteria established by the
      Diagnostic and Statistical Manual of Mental Disorders, fourth edition,
      hyperactivity in adolescents and adults may be limited to subjective feelings of
      restlessness. Recent studies with adults with ADHD have also reported that mental
      restlessness is commonly reported by individuals with the disorder. To better
      understand this characteristic of ADHD, the Internal Restlessness Scale (IRS) was
      developed. The results of the IRS suggest that (a) college students with ADHD
      report significantly higher ratings of internal restlessness than college
      students without ADHD, and (b) the IRS appears to have adequate test-retest
      reliability and a four-factor structure. Implications and suggestions for future
      research are discussed.

PMID- 15490910
TI  - Gaps and disparities in neonatal nursing care.

PMID- 15490911
TI  - Jarcho-Levin syndrome: a case study.
AB  - Jarcho-Levin syndrome is a rare genetic disorder characterized by multiple
      vertebral and rib anomalies. There are two types of Jarcho-Levin syndrome,
      spondylothoracic dysplasia and spondylocostal dysostosis. Spondylothoracic
      dysplasia has a grimmer prognosis than spondylocostal dysostosis. Many of the
      infants born with this disorder succumb to respiratory failure. With new advances
      in medical care, even the more severely affected children have an improved chance
      of survival. This is a case presentation of one child with spondylothoracic
      dysplasia and a brief history of the disease process.

PMID- 15490912
TI  - Intrauterine infections.

PMID- 15490913
TI  - NRP 2006: how revised guidelines develop.

PMID- 15490914
TI  - Comfort care of neonates at the end of life.
AB  - Most neonatal intensive care units have approaches to manage patients at the end
      of their lives. Published guidelines to help direct practitioners are lacking,
      and these management approaches, commonly referred to as comfort care, are often
      based on tradition. Recently, our neonatal staff experienced a unique situation
      that involved giving comfort care to a previable neonate who lived much longer
      than anticipated. Our staff identified the need for an evidence-based practice
      guideline to focus on four key care issues: provision of warmth, close physical
      contact, nutritional support, and sedation and pain management. The purpose of
      this article is to supply health care providers with evidence-based comfort care
      guidelines for neonates at the end of who either are previable of have had life
      support withdrawn. The process used for developing the guidelines is included.

PMID- 15490915
TI  - Kangaroo care: is it for everyone?
AB  - PURPOSE: In spite of the benefits reported for kangaroo holding, many mothers of
      preterm infants requiring intensive care do not choose to hold kangaroo style.
      The purpose of this study is to describe factors that influence mothers healthy
      preterm infants to choose kangaroo holding compared to the standard care method
      of blanket holding. SAMPLE: Twenty-four primiparous mother of healthy infants
      born at 30-34 weeks gestational age. DESIGN: In this naturalistic inquiry,
      mothers were interviewed twice: once while the infant was hospitalized and again
      after the infant was discharged home. RESULTS: Mothers' holding practices divided
      them into three groups: (1) kangaroo holding in hospital and home, (2) blanket
      holding in hospital and home, and (3) holding practice switched from hospital to
      home. Three themes emerged from the interview data: (1) emotional state, (2)
      holding environment, and (3) benefits of close contact with the infant.

PMID- 15490916
TI  - Swimming with sharks: ten tips for surviving a deposition.

PMID- 15490917
TI  - Selecting and using research instruments.
AB  - Many factors must be considered in planning and implementing research. Scientific
      reasons for decisions are important, but so are practical considerations. The
      suggestions made throughout this column are based on experience and may seem to
      some to be simply "common sense." However, the importance of these practical,
      common sense considerations cannot be minimized. These practical suggestions are
      intended to bring into focus the fact that the research process is not that
      different from other decision-making processes: In research as in life, there are
      multiple ways to get from point A to point B, and none of them is inherently
      right or wrong. The choices the researcher makes in designing and implementing a
      study must be clearly described and must be based on the research goals, the
      theoretical framework used, and the resources available. Potential nurse
      researchers should not be intimidated by the task at hand. Rather, they should be
      comforted by the fact that the same processes they use in making decisions about
      clinical practice can be employed in designing and implementing research studies.

PMID- 15490918
TI  - Smooth waters ahead?

PMID- 15490919
TI  - Walking the talk: an opportunity and a challenge.

PMID- 15490920
TI  - Lone motherhood and risk for cardiovascular disease: the National Population
      Health Survey (NPHS), 1998-99.
AB  - PURPOSE: To examine whether lone parenthood among Canadian women is associated
      with risk factors for cardiovascular disease (CVD). METHODS: The sample was from
      the National Population Health Survey (NPHS) and it included 2,184 mothers (women
      with dependent children < 18 years of age) of whom 478 were lone (22%) and 1,706
      (78%) were partnered mothers. Descriptive statistics and multiple logistic
      regression were undertaken with weighted data. RESULTS: Compared to partnered
      mothers, lone mothers were significantly younger, and reported lower levels of
      education and income. Lone mothers reported significantly lower levels of health,
      less social support, and more distress and depression than partnered mothers.
      Further, lone mothers were significantly more likely to be smokers than partnered
      mothers. Odds ratios for being a lone mother and current smoker on social
      assistance in this analysis was 4.15 (95% CI 2.27-7.60), and for those reporting
      low or mid/high incomes respectively, were 2.99 (1.51-5.90) and 3.01 (1.93-4.70).
      There were no significant differences between the two groups for obesity or
      physical activity. CONCLUSIONS: Smoking is a significant CVD lifestyle risk for
      lone mothers. Smoking occurred in the context of considerable life stress,
      depression, and distress pointing to links between health behaviour, psychosocial
      factors, and CVD health. These results suggest that lone mothers are a key target
      group for primary prevention in the CVD field. Programs and policies that support
      lone mothers in their goals of attaining healthier lifestyles have the potential
      to contribute to the prevention of cardiovascular disease in Canadian women.

PMID- 15490921
TI  - Declining use of mastectomy for invasive breast cancer in Canada, 1981-2000.
AB  - OBJECTIVE: To evaluate the rate and magnitude of change in surgical practice for
      breast cancer in Canada in relation to publication dates of clinical trials and
      consensus conferences. METHODS: Hospital separations with a diagnosis of invasive
      breast cancer were extracted from the Hospital Morbidity File from 1981 to 2000.
      Age-standardized rates of in-patient procedures for breast-conserving surgery and
      mastectomy were analyzed by province and age group and by geographic region.
      RESULTS: In Canada, mastectomy rates decreased from 62.2 to 37.9 per 100,000
      between 1981 and 2000; declines were largest between 1984 and 1985, following
      publication of the NSABP B-06 clinical trial in March 1985, and between 1991 and
      1993, after the US NIH Consensus Conference in February 1991. Mastectomy rates
      plateaued between 1985 and 1991, and from 1993 to 2000; the transitory peak in
      1988 corresponded to publicity surrounding Nancy Reagan's choice of mastectomy in
      1987. Regional variations from the main pattern led to increasingly divergent
      mastectomy rates over time. Women aged 80+ were less likely to be treated by any
      surgery. INTERPRETATION: Publication of clinical trial results and consensus
      conferences were associated with changes in surgical treatment for breast cancer
      in Canada. However, divergent mastectomy rates among Canadian regions point to
      inconsistent adoption of less invasive therapy despite a publicly-funded health
      care system and national consensus guidelines.

PMID- 15490922
TI  - Waiting time for breast cancer treatment in Alberta.
AB  - BACKGROUND: The present study had two research questions. First, what is the
      average waiting time between diagnosis and treatment for Alberta women with
      breast cancer relative to Canadian Society for Surgical Oncology (CSSO)
      recommendations? Second, does patient age, cancer stage, patient community size,
      and year of diagnosis have a significant relationship to waiting time? METHODS:
      The sample consisted of all Alberta women diagnosed with breast cancer between
      1997 and 2000. Waiting time was defined as number of days between definitive
      diagnosis and treatment initiation. Multiple regression examined the relative
      influence of the predictor variables on waiting time. RESULTS: There were 6,418
      cases of breast cancer between 1997 and 2000. Mean waiting time was 20.2 days (SD
      21.6) and median waiting time was 17 days. Longer waiting time was significantly
      associated with year of diagnosis (progressively longer from 1997 to 2000),
      patients younger than 70, and Stage 1 cancer. Waiting time increase from 1997 to
      2000 appears to be due to increased demand for services without corresponding
      increases in resources. Less treatment delay for women older than 70 is due to
      more of these women being treated the same day they received their diagnosis.
      CONCLUSION: Only 44% of women had a waiting time of 14 days or less as
      recommended by the CSSO. The number of women who will have to wait longer than
      recommended for treatment will likely increase without a significant increase in
      oncological resources. The basis for differences in waiting times as a function
      of age needs to be further investigated to ensure equitable access to care.

PMID- 15490923
TI  - Access to colposcopy services for high-risk Canadian women: can we do better?
AB  - BACKGROUND: Despite overall decreasing mortality from cervical cancer, selected
      groups of Canadian women continue to have suboptimal access to diagnostic and
      treatment interventions for cervical cancer. In this paper, we present an
      evaluation of a colposcopy program developed to improve attendance for colposcopy
      in a lower socio-economic and immigrant population. METHODS: All women attending
      the North Hamilton Community Health Centre (CHC) who required colposcopic
      assessment and were referred to a newly developed colposcopy program based at the
      CHC were evaluated. Attendance rates for consultation, follow up and treatment in
      women referred for colposcopy were compared retrospectively for the CHC-based
      colposcopy program and concurrently with the regional colposcopy clinic (RCC).
      RESULTS: Women referred to the CHC colposcopy program had a significant reduction
      in their no-show rate after the introduction of the locally based colposcopy
      program (17.2% vs. 1.3%, p<0.01). Comparing the same time periods, there was no
      significant reduction in the default rate at the RCC (2.5% vs. 3.3%, p=0.21).
      Despite serving a population of women who were at higher risk for non-attendance,
      patients at the CHC had a default rate for appointments similar to that of the
      RCC (1.3% vs. 3.3%, p=0.55) after the introduction of the local colposcopy
      program. CONCLUSIONS: Lower socio-economic status and immigrant women receiving
      care from a CHC-based colposcopy program had a significant decrease in their no
      show rate for colposcopic evaluation after the introduction of the on-site
      program. Consideration must be given to locating diagnostic colposcopy programs
      in settings more accessible to women who require these services the most.

PMID- 15490924
TI  - Youth at risk of homelessness in an affluent Toronto suburb.
AB  - BACKGROUND: This study examines the characteristics and needs of 69 youth who are
      homeless, or at risk of homelessness at Pathway's Home Base Youth Drop-In Centre
      in the affluent suburb of Richmond Hill, Ontario, Canada. METHODS: A semi
      structured interview examined demographics, characteristics, living arrangements,
      family characteristics, substance use, mental health, criminal activity and
      educational experiences of the youth in this sample. RESULTS: The majority of
      youth came from economically advantaged families and were currently residing with
      their parents, but were substantially more at risk than their mainstream peers in
      measures related to youth homelessness. The majority of Home Base youth had left
      home and school prematurely, been arrested in their lifetime, and used at least
      one illicit drug in the past 12 months. A substantial number of youth had been
      imprisoned, experienced physical abuse, and exhibited depressive symptomatology
      and suicidal ideation. CONCLUSION: Although living mainly at home and in a
      relatively affluent suburb, these youth have many attributes related to
      homelessness and may progress to homelessness without intervention.

PMID- 15490925
TI  - Adolescent suicide in Quebec and prior utilization of medical services.
AB  - BACKGROUND: Psychopathology is the main risk factor for adolescent suicide but
      several studies have shown that only a small proportion of suicide victims
      receive mental health care during the months preceding their suicide. The goal of
      this study is to describe the utilization of medical services by Quebec
      adolescent suicide victims during the year preceding their suicide. METHODS: All
      suicides of persons aged 19 or less that occurred during a five-year period were
      retrieved from the Quebec Coroner's database. Corresponding medical services
      utilization data were retrieved from the Quebec physician payment database (RAMQ)
      and the Quebec hospitalization database (MED-ECHO). Data were analyzed in terms
      of types and intensity of medical services (physical or psychiatric), types of
      providers (general practitioners, psychiatrists, and other medical specialists),
      and timing of interventions relative to the date of suicide. RESULTS: 78% of all
      Quebec adolescent suicide victims utilized medical services during the year
      before their suicide. However, only 12% of all victims received medical attention
      for psychiatric problems, and only 9.9% met with a psychiatrist during that same
      period of time. General practitioners and non-psychiatric medical specialists
      provided medical attention for psychiatric problems to only 5.6% and 0.7% of
      those future suicide victims with whom they met in outpatient settings, and the
      intensity of their interventions was low. INTERPRETATION: These results suggest
      that the level of recognition and treatment of psychopathology in Quebec
      adolescents who later commit suicide is low, despite the fact that a large
      proportion of them meet with physicians during the year preceding their suicide.
      This suggests that information and training programs pertaining to adolescent
      suicide and psychopathology should be implemented for GPs and non-psychiatric
      medical specialists as well.

PMID- 15490927
TI  - Identifying and addressing the social determinants of the incidence and
      successful management of type 2 diabetes mellitus in Canada.

PMID- 15490926
TI  - Traumatic experiences in childhood and the risk of arthritis: a prospective
      cohort study.
AB  - BACKGROUND: Recent data suggest that psychosocial factors, including childhood
      and adulthood stressors, may play a significant role in the development of
      chronic musculoskeletal pain and other symptoms. The purpose of this study was to
      determine if traumatic experiences in childhood are associated with an increased
      risk of self-reported arthritis later in life. METHODS: We used longitudinal data
      (N=9,159) from the first 3 cycles of the National Population Health Survey (NPHS)
      in Canada. New cases of arthritis were identified using an interviewer
      administered questionnaire. Psychological trauma in childhood or adolescence was
      measured by a 7-item questionnaire asking about physical abuse, fearful
      experiences, hospitalization, being sent away from home, and 3 types of parental
      disturbance. The effects of trauma were examined in a multivariable discrete-time
      proportional hazards model. RESULTS: The incidence of self-reported arthritis was
      27.1 per 1,000 person-years. We found a relative risk of 1.17 (95% CI=0.92, 1.48)
      for one traumatic event and 1.27 (95% CI=0.99, 1.62) for two or more traumatic
      events. Independent effects were observed for prolonged hospitalization (HR=1.33,
      95% CI=1.05, 1.68) and being very scared (HR=1.29, 95% CI=1.02, 1.62). In
      subgroup analyses, no significant interactions were found between trauma and sex,
      socio-economic status, or baseline health. CONCLUSIONS: In this large prospective
      study, we found a moderate increase in the risk of arthritis among persons
      reporting multiple traumatic experiences in childhood.

PMID- 15490928
TI  - Morbidity and mortality rates in a NOVA SCOTIA First Nations Community, 1996
      1999.
AB  - BACKGROUND: Despite an abundance of data and analysis of First Nations morbidity
      and mortality rates, accurate data have not been available to serve the First
      Nations community in Eastern Canada. METHODS: Data for Eskasoni, the largest
      Mi'kmaq community, were obtained for 1996 through 1999 and Cape Breton and Nova
      Scotia were used as regional and provincial reference populations respectively.
      Age-adjusted relative risks (AARR) were calculated for overall mortality and
      disease-specific hospital admissions. RESULTS: Eskasoni's mortality AARR was
      greater than 1.0 in 3 of the 4 years studied, although the data may understate
      Eskasoni's mortality rates. Eskasoni's total admission AARRs were significantly
      greater than the two reference populations. Neoplasm admission rates were
      generally lower, while circulatory disease admission AARRs were significantly
      higher. A rise in diabetic admission rates was noted with the AARR reaching
      statistical significance in the final years of the study. Respiratory disease was
      the leading cause of hospitalization with significantly greater rates of
      admission than regional or provincial rates. Pneumonia and influenza accounted
      for more than one half of respiratory admissions. Infectious disease admissions
      were more prevalent in Eskasoni while rates of liver disease were generally low.
      CONCLUSION: Results suggest that members of the largest Mi'kmaq band are at
      greater risk for a number of disease categories and health promotion should be
      targeted toward respiratory ailments, circulatory disease and diabetic
      management. Further analysis, however, remains an important priority.

PMID- 15490929
TI  - Public nutrition: an emerging paradigm.

PMID- 15490930
TI  - [Influenza prevention, surveillance, and control in long term care facilities].
AB  - OBJECTIVE: Describe the implementation of various activities suggested in the
      guide entitled Prevention, surveillance et controle de l'influenza en milieu
      d'hebergement et de soins de longue duree (CHSLD) au Quebec, distributed in 2000
      to Montreal-area CHSLD. METHOD: The study was conducted in 2001 among 57 CHSLDs
      (39 public institutions and 18 private institutions under agreement) in Montreal.
      A self-administered questionnaire collected data on the characteristics of the
      centres and main activities recommended in the guide. The principal activities
      recommended were grouped into three components: influenza prevention,
      surveillance and control. Data were entered and analyzed using SPSS 10.0. A
      descriptive analysis was performed. RESULTS: The overall rate of response was 81%
      (46/57). The proportion of centres that had carried out the various components
      was 35% (16/46) for prevention and 41% (19/46) for surveillance; only 2 centres
      had applied the influenza control component. CONCLUSION: Over half of CHSLDs in
      Montreal did not implement the influenza prevention, surveillance and control
      components. Gaps were noted, especially related to vaccine coverage of staff and
      rapid access to chemoprophylaxis. Several additional control measures recommended
      were also considered to be inapplicable. We must review our strategies to
      identify the barriers to optimal implementation of these measures.

PMID- 15490931
TI  - Long-term-care residents: concerns identified by population and care trends.
AB  - OBJECTIVE: Despite rising concern over population aging, few descriptions exist
      of long-term-care (LTC) residents, the people who are normally the oldest and the
      most dependent persons. This study sought to describe a LTC resident population
      and trends in this population. METHODS: A descriptive-comparative quantitative
      analysis of all data (1988-1999) from a provincial (Alberta) LTC resident
      database was undertaken. FINDINGS: Over the 10-year period, there was a
      significant increase in care needs. In the 1988, the mean Requirement Score was a
      "C" (indicating low to medium level care was required); by the 1999, the mean
      score was "E" (medium to high level care). There were both a substantial
      reduction in residents with low care needs and an increase in residents with high
      care needs. Although the mean age of LTC residents increased from 80.5 to 82.5,
      residents under age 65 had higher care needs. General linear modelling also
      revealed younger age was a significant influence in regard to higher care needs,
      along with larger (versus smaller) LTC admission to death also declined
      significantly from 6.9 to 3.4 years. Although this study may only confirm what is
      suspected about LTC residents, it should raise discussion over the impact of
      limited LTC beds on families, community-based health services, and acute care
      hospitals; and the implications of more dependent residents on LTC facility and
      personnel planning [corrected]

PMID- 15490932
TI  - Stability of normative data for the SF-36: results of a three-year prospective
      study in middle-aged Canadians.
AB  - BACKGROUND: The SF-36 is widely used to assess health-related quality of life
      (HRQOL), but with few longitudinal studies in healthy populations, it is
      difficult to quantify its natural history. This is important because any measure
      of change following an intervention may be confounded by natural changes in
      HRQOL. This paper assesses mean changes in SF-36 scores over a 3-year period in
      men and women between the ages of 40 and 59 years at baseline. METHODS: Subjects
      were randomly selected from nine Canadian cities. Mean SF-36 changes over a 3
      year period (1996/1997-1999/2000) were calculated for each gender within 5-year
      age categories. Multiple imputation was used to correct for potential bias due to
      missing data. RESULTS: The baseline cohort included 1,974 women and 975 men
      between 40 and 59 years. Mean changes in HRQOL tended to be small. Women
      demonstrated small average declines in 22 of the 32 age and domain groupings (4
      age groups, 8 SF-36 domains) while men showed declines in 14/32. Most
      participants stayed within 10 points of their original baseline score.
      INTERPRETATION: Mean SF-36 scores change only slightly over three years in middle
      aged Canadians, although there is much individual variation. It may be necessary
      to adjust for the natural evolution of SF-36 scores when interpreting results
      from longitudinal studies.

PMID- 15490933
TI  - Advancing the population health agenda: encouraging the integration of social
      theory into population health research and practice.

PMID- 15490934
TI  - [Clinical peculiarities of optic neuritis and alterations of local immune
      response in patients with multiple sclerosis].
AB  - Multiple sclerosis (MS) is a severe organic disease of the central nervous system
      (CNS) affecting mostly young people. Optic neuritis (ON) is one of the first
      manifestations of the disease in approximately 75% of cases. The autoimmune
      reactions to myelin antigens play a key role in ON pathogenesis of MS. The pro-
      and anti-inflammatory unbalance is the most important factor of the origin,
      development and stabilization of CNS changes. Presented are the data on
      alterations of the levels of pro- and anti-inflammatory cytokines TNF-alpha, IF
      gamma and antibodies to MBP and anti DNA in patient's tears. The clinical
      peculiarities of ON in MS correlating with immunological alterations are
      established.

PMID- 15490935
TI  - [The background for development of refusal reactions in schizophrenics].
AB  - Eighty-five patients (52 male, 33 female, mean age 28.9 years) with slowly
      progressive schizophrenia with predominantly positive (pseudopsychopathic type,
      ICD-10 item F21.4)--79 patients and/or predominantly negative ("poor symptoms"
      schizophrenia, F20.6)--6 patients symptoms, were studied. All patients referred
      to the psychiatric clinic with refusal reactions. Depending on the psychological
      and behavioral mechanisms developing on the base of negative changes the refusal
      reactions have been divided into capitulation, avoidance and absenteeism
      subtypes. Their clinical heterogeneity was determined by the ratio of structure
      of schizophrenia-related personality disorders and cognitive deficit. Negative
      disorders in capitulation refusal reaction manifest in patients as "psychosthenic
      like" personality with accentuation of dependent personality features and
      operational cognitive deficit. Avoidance subtype was observed in patients with
      schizoid (autistic or eccentric) personality changes and predominantly dynamic
      cognitive deficit. Absenteeism subtype was found in weak-will individuals and
      mainly motivational cognitive deficit.

PMID- 15490936
TI  - [Clinico-neurophysiologic and experimental study of the peculiarities of
      adamantan-sulphate treatment in Parkinson's disease].
AB  - An experimental investigation of parkinsonism in rats and patients with initial
      forms of Parkinson's disease was performed by using methods of electromyography
      and electroneuromyography. Neurophysiologic peculiarities of reorganization of
      peripheral neuromotor apparatus and criteria for treatment efficacy were
      detected. The results obtained in the study allowed evaluating of an adequacy of
      adamantan-sulphate therapy either in the animal experiments and in patients with
      Parkinson's disease.

PMID- 15490937
TI  - [Interferon-beta treatment in patients with childhood-onset and juvenile multiple
      sclerosis].
AB  - Prospectively observed natural history in 10 cases of pediatric multiple
      sclerosis (MS), with respect to prognosis comparing to that of adult-onset MS
      (n=100) is presented. Poor-prognosis with severe disability was found in juvenile
      MS (age at onset 10-16 years old) with high annual rate of relapses in 2 years
      after the disease onset. The results of the long-term (2.0 to 3.5 years) beta
      interferon treatment in patients with juvenile MS and the factors affecting these
      results are analyzed. Based on these data, together with those of published
      controlled clinical trials in adult-onset MS, indications for beta-interferon
      therapy and peculiarities of the treatment are discussed.

PMID- 15490938
TI  - [Preventive efficacy of tianeptine in recurrent depression with frequent
      exacerbations].
AB  - The results of the studies of 4 Russian research centers are summarized.
      Tianeptine (coaxil) was used in the treatment of 55 patients with ICD-10
      diagnosis of recurrent depressive disorder (F32.1), 50 patients have completely
      finished the treatment. Tianeptine was assigned in dosage of 12.5 mg 3 times
      daily (patients over 65 years old received 25.0 mg daily) during 12 months. The
      drug was shown to have a high preventive efficacy for the disorder. Sixty-one
      percent of patients were full-responders. Taken together with partial responders
      (13%), an improvement was observed in 74% patients. The drug demonstrated a well
      tolerability with a rare and mild expression of side-effects.

PMID- 15490939
TI  - [Use of cypramil in the treatment of depression in patients with gastrointestinal
      cancer].
AB  - Depressive state in cancer patients is known to meet the criteria of mild
      depressive episode (F33.0) according to ICD-10. In the earlier stages of the
      disease and after successful treatment, depressive symptoms are usually combined
      with anxiety and obsessive fear, moderate appearances of ideator and motor
      inhibition, with permanent presence of asthenic symptoms. Once the disease is
      getting severer and the treatment is less successful, asthenia acquires
      hyposthenic features, with symptoms of apathy and dysphoria being attached.
      Cypramil was shown to be an effective medication in the treatment of depression
      in patients with malignant tumors of gastric-intestinal tract. The most efficient
      was the treatment conducted on the earlier stages of the cancer process and in
      cases of successful surgery and chemotherapy, in combination of depression with
      anxiety, anxious hypochondria, asthenia. Antidepressants must be used together
      with psychotherapy.

PMID- 15490940
TI  - [Theatre systems as a basis for developing medical and rehabilitation methods in
      psychiatry].
AB  - On the basis of existing and widely used in theatrical practice systems, a new
      direction in medical and rehabilitation psychiatry, namely transdramatherapy, was
      developed. The approach is illustrated by the original psychotherapeutic method
      of epos therapy directed to treatment of neurotic disorders, which has been
      already created and approbated.

PMID- 15490941
TI  - [Immunological indices in schizoaffective and affective psychoses].
AB  - Proliferative activity of peripheral blood lymphocytes has been studied in
      patients with schizoaffective (18) and affective (24) psychoses in 4 experimental
      variants: cultivation of blood lymphocytes isolated by centrifuging in the
      density gradient with fetal (1st variant) or autologic serum (2nd variant);
      cultivation of lymphocyte obtained in plasma sedimentation with fetal (3rd
      variant) and autologic serum (4th variant). A level of functional lymphocyte
      activity was significantly decreased in patients. The data obtained suggest that
      different mechanisms underlie this decrease. In schizoaffective psychosis, a
      disturbance of cell cooperative interaction in immune response was observed. In
      affective psychosis, the determining factors were a decrease of the ability of
      lymphocytes to respond to mytogenic stimulation and a presence of the factor
      inhibiting a functional activity of lymphoid cells in patient's blood. Besides,
      it was shown that in patients with schizoaffective psychosis, lymphocyte
      proliferative activity inversely correlates with the disease duration and in
      affective patients the direct correlation between these indices was detected.

PMID- 15490942
TI  - [Betaserc in the treatment of vestibular disorders in syndrome of vegetative
      dystonia].

PMID- 15490943
TI  - [Karl Leongard (to 100th anniversary of birth)].

PMID- 15490944
TI  - [A case of spinal muscle atrophy with lesions of hand and thigh muscles].

PMID- 15490945
TI  - [A case of severe vomitomania in a female patient with anorexia nervosa].

PMID- 15490946
TI  - [Serotonin metabolism dysfunction in pathogenesis of nervous system disorders].

PMID- 15490947
TI  - [Family as a field of interaction of the risk and protection factors in
      psychoactive compounds addiction by adolescents].

PMID- 15490948
TI  - What about expert witnesses?

PMID- 15490949
TI  - Kenneth Lynch and asbestos.

PMID- 15490950
TI  - An update on the medical workforce in South Carolina: its current status and
      another look to the future.

PMID- 15490951
TI  - Prophylactic beta-blocker use to prevent perioperative morbidity and mortality.
AB  - Cardiovascular disease continues to be a major health concern and leads to
      significant perioperative morbidity and mortality. Evidence for prophylactic use
      of beta-blockade to decrease these complications continues to grow. Not all
      patients benefit from perioperative beta-blockade, thus a thorough preoperative
      cardiac assessment should be performed with every patient undergoing surgery.
      Although physicians may have doubts with this new strategy, the literature
      overwhelmingly supports prophylactic beta-blockade use as a safe, efficacious,
      and cost effective new therapy in patients at risk for cardiac complications.

PMID- 15490952
TI  - The symbols used to represent the field and practice of medicine.

PMID- 15490953
TI  - The effect of Medicaid cuts on South Carolina's economy: a study of federal
      funds.

PMID- 15490954
TI  - Advancing medical professionalism. III. Bearding the evils of specialization.

PMID- 15490955
TI  - Health maintenance organization (HMO) performance and consumer complaints: an
      empirical study of frustrating HMO activities.
AB  - Growing public interest in the operations of managed care plans has fueled a
      variety of activities to collect and analyze their performance. These activities
      include studies of financial performance, analysis of enrollment decisions, and,
      more recently, the development of systems for measuring healthcare quality to
      improve accountability to consumers. In this study, the authors focus on the
      activities of managed care plans that may frustrate patients and providers and,
      subsequently, motivate patients to file complaints. Using data from three
      sources, they evaluate the relationships between complaints against managed care
      plans and two metrics of performance: (a) the financial performance of the plan,
      and (b) the quality of care provided. Their findings indicate that complaints
      against health maintenance organizations are significantly related to the plans'
      levels of quality and to actions that may impede access to care.

PMID- 15490956
TI  - Value-chain analysis of a rural health program: toward understanding the cost
      benefit of telemedicine applications.
AB  - While telemedicine's clinical effectiveness and educational benefits are
      accepted, its cost-effectiveness is controversial. This study focuses on
      telemedicine's cost-effectiveness from a provider's perspective. Reviews of the
      cost-effectiveness literature in telemedicine are critical of past studies' (a)
      methodological and analytical weaknesses; (b) focus on answering "Can we do
      this?" rather than "Should we do this?"; and (c) emphasis on patient benefits.
      Value chain analysis examines structural and executional cost drivers; a self
      sustaining business model balances the cost and value associated with each
      telemedicine activity. We illustrate this analysis in a rural health program,
      examining teleradiography and telerehabilitation.

PMID- 15490957
TI  - CEO's perceptions of hospitalists: diffusion of the strategy.
AB  - Many hospitals have initiated a strategy to reduce costs and improve quality of
      care by using physicians as "hospitalists." A hospitalist specializes in
      inpatient care. This article reports the findings of survey research examining
      CEO perceptions of the hospitalist model, with particular interest in diffusion
      of the strategy in rural and low managed care hospital markets. Findings indicate
      there is less diffusion of the hospitalist model to rural areas because of lack
      of information about the cost effectiveness of the program and medical staff
      resistance. Recommendations to increase adoption of the hospitalist strategy
      include educating about the benefits of the strategy and paying attention to
      areas of concern by the medical staff.

PMID- 15490958
TI  - One more time: improve your board through self-assessment.
AB  - Evaluating board effectiveness is a highly subjective, individualized, and
      potentially powerful undertaking if pursued with the proper motivation and with
      the ownership of the board. In this article, the authors describe one successful
      approach to board self-evaluation pursued by the Albert Lea Medical Center, Mayo
      Health System, Minnesota. The authors share evaluation methodology as well as
      process and outcomes. Recommendations directed toward organizations considering
      the self-evaluation process are formed around three themes. First, engage your
      board and have them own the process. Second, engage your board in developing the
      evaluation methodology. Third, ensure accountability in the board and the senior
      organization leadership for action on self-assessment outcomes. Finally, the
      authors discuss board development as a functional responsibility of the board. In
      that context, they present self-evaluation as one opportunity for a board to
      tangibly embrace its education and development responsibilities.

PMID- 15490959
TI  - Going, going,... all but gone.

PMID- 15490960
TI  - Hospitals' movements toward the electronic medical record: implications for
      nurses.

PMID- 15490961
TI  - Verbal abilities in low and highly proficient bilinguals.
AB  - The study investigated native language verbal skills among low and highly
      proficient bilinguals, using the WISC III verbal subtests. Highly proficient
      bilinguals showed a superiority for almost all verbal subtests. This finding
      lends support to Threshold Theory which maintains that bilinguals need to achieve
      high levels of linguistic proficiency before bilingualism can promote cognitive
      development. Our study also shows that verbal ability underlying proficiency in
      the native language can be generalized to a foreign language, revealing a causal
      connection between native and foreign language learning.

PMID- 15490962
TI  - Stem complexity and inflectional encoding in language production.
AB  - Three experiments are reported that examined whether stem complexity plays a role
      in inflecting polymorphemic words in language production. Experiment 1 showed
      that preparation effects for words with polymorphemic stems are larger when they
      are produced among words with constant inflectional structures compared to words
      with variable inflectional structures and simple stems. This replicates earlier
      findings for words with monomorphemic stems (Janssen et al., 2002). Experiments 2
      and 3 showed that when inflectional structure is held constant, the preparation
      effects are equally large with simple and compound stems, and with compound and
      complex adjectival stems. These results indicate that inflectional encoding is
      blind to the complexity of the stem, which suggests that specific inflectional
      rather than generic morphological frames guide the generation of inflected forms
      in speaking words.

PMID- 15490963
TI  - A time course view of sentence priming effects.
AB  - Meaning activation was estimated during (standard naming) and after (delayed
      naming) target presentation to chart the time course of priming effects during
      reading comprehension. Using sentences biasing homographs toward their dominant
      and subordinate meanings, two experiments evaluated context effects across three
      naming-cue delays: immediate, baseline, baseline + 600ms all at a 0-ms
      interstimulus interval. When participants named a target immediately as it was
      presented, results converged with previous findings demonstrating initial context
      sensitive meaning activation. The delayed naming conditions revealed little post
      access influences for dominant contexts. Subordinate contexts, however, provided
      the strongest evidence of continued (or sustained) processing. It was concluded
      that context has immediate and automatic effects on initial meaning activation,
      after which, strategies are invoked for fine-tuning an interpretation of a
      sentence and integrating it with new information.

PMID- 15490964
TI  - Describing the acquisition of determiners in English: a growth modeling approach.
AB  - This paper, based on naturalistic data, describes the acquisitional course and
      use of the articles a and the in young English-speaking children (18-61 months),
      with special emphasis on the role of individual variation. A growth modeling
      approach to the data reveals that children's individual acquisition schedules are
      similar in trend, but vary in the rate at which they omit determiners at a given
      point of time. This picture suggests that an analysis that presumes homogeneous
      development will seriously misrepresent the fluctuations between and within
      individuals. Interestingly, this variation does not reflect a variation in
      children's abilities to use determiners correctly-irrespective of the rate in
      which they used determiners, children seldom used determiners incorrectly. The
      analysis also reveals that children's optional omission of determiners in
      obligatory contexts, beginning at 18 months of age, gradually decreases on
      average by 3-4% a month until 36 months of age, and thereafter plunges by a
      factor of 10 to an average of 0.3% per month. At 36 month of age the majority of
      children use determiners at a near-mastery level (Brown, 1973). These findings
      provide a useful framework for theorizing about possible mechanisms underlying
      the nature of early language development pre- and post-36 months of age.

PMID- 15490965
TI  - Borderline science: expert testimony and the Red River boundary dispute.
AB  - The 1918 discovery of oil in the bed of the Red River, which forms the border
      between Texas and Oklahoma, led to a U.S. Supreme Court case that involved the
      extensive use of expert witnesses in fields such as geology, geography, and
      ecology. What began as a dispute between the two states soon became a multisided
      controversy involving those states, the federal government, Native Americans, and
      individual placer-mining claimants. After the federal attorneys introduced
      scientific experts into the dispute, including the plant ecologist Henry Chandler
      Cowles and the geographer Isaiah Bowman, fresh from negotiations at the Paris
      Peace Conference, Texas attorneys fielded their own team of opposing experts.
      Charged with the task of determining the location of the border, defined as the
      south bank of the river at the time of the 1819 treaty with Spain, the scientific
      experts presented the court with volumes of evidence and elaborate arguments,
      much of it contradictory and involving creative interpretations of existing
      theories. The case exhibited all the now-familiar features of a trial using
      expert witnesses, for which it represents an early, overlooked, and particularly
      complex example.

PMID- 15490966
TI  - Ancient scientific basis of the "great serpent" from historical evidence.
AB  - Zoological data and a growing mythology contributed to ancient Western knowledge
      about large serpents. Yet little modern attention has been paid to the sources,
      transmission, and receipt in the early Middle Ages of the ancients' information
      concerning "dragons" and "sea serpents." Real animals--primarily pythons and
      whales--lie behind the ancient stories. Other animals, conflations of different
      animals, simple misunderstandings, and willful exaggerations are found to account
      for the fanciful embellishments, but primitive myths played no significant role
      in this process during classical times. The expedition of Alexander the Great
      into India (327-325 B.C.) and the Bagradas River incident in North Africa (256
      B.C.) had enormous repercussions on the development of serpent lore. Credible
      evidence is found for the presence of ancient populations of pythons living along
      the North African coast west of Egypt and along the coast of the Arabian Sea
      between the Indus River and the Strait of Hormuz--places where they no longer
      exist today. The maximum sizes of ancient pythons may have been greater than
      those of today's specimens.

PMID- 15490967
TI  - Chrysophiles versus chrysophobes: the white asbestos controversy, 1950s-2004.
AB  - In the first half of the twentieth century, asbestos was a controversial mineral
      because of its association with asbestosis and asbestos-related lung cancer. It
      has proved no less so since the 1960s, when another asbestos cancer,
      mesothelioma, was identified. Mesothelioma appeared to be more strongly linked
      with blue asbestos (crocidolite) than with the other asbestos varieties, brown
      (amosite) and white (chrysotile). This finding triggered a fierce debate between
      "chrysophiles" (those who declared chrysotile innocuous) and "chrysophobes"
      (those who believed it was a mortal hazard). This essay attempts the first
      history of the chrysotile controversy, which shows that a scientific consensus on
      the safety of white asbestos was very slow to emerge. This was only partly due to
      the complexities of scientific research. Political, economic, and social factors
      have militated against a speedy resolution of the debate, facilitating the
      continued production and use of asbestos in the developing world.

PMID- 15490968
TI  - Molecular biology and DNA microarray technology for microbial quality monitoring
      of water.
AB  - Public concern over polluted water is a major environmental issue worldwide.
      Microbial contamination of water arguably represents the most significant risk to
      human health on a global scale. An important challenge in modern water microbial
      quality monitoring is the rapid, specific, and sensitive detection of microbial
      indicators and waterborne pathogens. Presently, microbial tests are based
      essentially on time-consuming culture methods. Rapid microbiological analyses and
      detection of rare events in water systems are important challenges in water
      safety assessment since culture methods present serious limitations from both
      quantitative and qualitative points of view. To circumvent lengthy culture
      methods, newer enzymatic, immunological, and genetic methods are being developed
      as an alternative. DNA microarray technology is a new and promising tool that
      allows the detection of several hundred or even thousands DNA sequences
      simultaneously. Recent advances in sample processing and DNA microarray
      technologies provide new perspectives to assess microbial water quality. The aims
      of this review are to (1) summarize what is currently known about microbial
      indicators, (2) describe the most important waterborne pathogens, (3) present
      molecular methods used to monitor the presence of pathogens in water, and (4)
      show the potential of DNA microarrays in water quality monitoring.

PMID- 15490969
TI  - The physiological role of ferritin-like compounds in bacteria.
AB  - Iron, as the ferrous or ferric ion, is essential for the life processes of all
      eukaryotes and most prokaryotes; however, the element is toxic when in excess of
      that needed for cellular homeostasis. Ferrous ions can react with metabolically
      generated hydrogen peroxide to yield toxic hydroxyl radicals that in turn degrade
      lipids, DNA, and other cellular biomolecules. Mechanisms have evolved in living
      systems for iron detoxification and for the removal of excess ferrous ions from
      the cytosol. These detoxification mechanisms involve the oxidation of excess
      ferrous ions to the ferric state and storage of the ferric ions in ferritin-like
      proteins. There are at least three types of ferritin-like proteins in bacteria:
      bacterial ferritin, bacterioferritin, and dodecameric ferritin. These bacterial
      proteins are related to the ferritins found in eukaryotes. The structure and
      physical characteristics of the ferritin-like compounds have been elucidated in
      several bacteria. Unfortunately, the physiological roles of the bacterial
      ferritin-like compounds have been less thoroughly studied. A few studies
      conducted with mutants indicated that ferritin-like compounds can protect
      bacterial cells from iron overload, serve as an iron source when iron is limited,
      protect the bacterial cells against oxidative stress and/or protect DNA against
      enzymatic or oxidative attack. There is very little information available
      concerning the roles that ferritin-like compounds might play in the survival of
      bacteria in food, water, soil, or eukaryotic host environments.

PMID- 15490970
TI  - The adenylate cyclase toxins.
AB  - Cyclic AMP is a ubiquitous messenger that integrates many processes of the cell.
      Diverse families of adenylate cyclases and phosphodiesterases stringently
      regulate the intracellular concentration of cAMP. Any alteration in the cytosolic
      concentration of cAMP has a profound effect on the various processes of the cell.
      Disruption of these cellular processes in vivo is often the most critical event
      in the pathogenesis of infectious diseases for animals and humans. Many
      pathogenic bacteria secrete toxins to alter the intracellular concentration of
      cAMP. These toxins either disrupt the normal regulation of the host cell's
      adenylate cyclases/phosphodiesterases or they themselves catalyze the synthesis
      of cAMP in the host cell. The latter are known as the adenylate cyclase toxins.
      Four such toxins have been identified: the invasive adenylate cyclase of
      Bordetella pertussis, the edema factor of Bacillus anthracis, ExoY of Pseudomonas
      aeruginosa, and the adenylate cyclase of Yersinia pestis. These adenylate cyclase
      toxins enter the eukaryotic host cells and get activated by eukaryotic cofactors,
      like calmodulin, to trigger the synthesis of cAMP in these cells. By accumulating
      cAMP in the target cells, these toxins either modulate the cellular function or
      completely deactivate the cell for further function. The immune effector cells
      appear to be the primary target of these adenylate cyclase toxins. By
      accumulating cAMP in the immune effector cells, these adenylate cyclase toxins
      poison the immune system and thus facilitate the survival of the bacteria in the
      host.

PMID- 15490971
TI  - Decontamination techniques of pathogen bacteria in meat and poultry.
AB  - Means of controlling or even improving the safety of food products is to
      decontaminate the carcasses or products during or at the end of the production
      line. The decontamination of meat and poultry can help to reduce human foodborne
      infections. However, process hygiene to prevent contamination should never be
      neglected. Some techniques of decontaminating raw meat and poultry meat products
      are discussed in this review.

PMID- 15490972
TI  - 4-[3,5-Bis(trimethylsilyl)benzamido] benzoic acid inhibits angiogenesis in colon
      cancer through reduced expression of vascular endothelial growth factor.
AB  - 4-[3,5-bis(trimethylsilyl)benzamido] Benzoic acid (TAC-101) has potent
      antiproliferative, antiangiogenic, and antitumor effects in vitro and in vivo.
      These effects might be due to TAC-101 binding to retinoic acid receptor alpha
      (RAR-alpha) and interfering with the binding of activator protein-1 (AP-1) to
      DNA. However, little is known about the detailed mechanism of TAC-101 function.
      We investigated the mechanism of the antiangiogenic effect of TAC-101 using a rat
      hepatic metastatic model in vivo and DLD-1 human colon cancer cells in vitro.
      Liver metastases were induced by portal injection of RCN-9 rat colonic cancer
      cells into F344 rats. TAC-101 (8 mg/kg) was orally administered 5 days per week
      for 4 weeks and then hepatic tumors were immunohistochemically evaluated for
      microvessel density (MVD) and vascular endothelial growth factor (VEGF). TAC-101
      significantly reduced both MVD and VEGF expression. Northern blot analysis and
      ELISA indicated that TAC-101 efficiently inhibited production of VEGF mRNA and
      protein in DLD-1 cells in a time- and dose-dependent manner. These findings
      suggest that TAC-101 may inhibit progression and metastasis in colon cancer by
      interfering with tumor production of VEGF.

PMID- 15490973
TI  - Resveratrol and propolis as necrosis or apoptosis inducers in human prostate
      carcinoma cells.
AB  - Vegetables and fruit help the prevention and the therapy of several kinds of
      cancer because they contain micronutrients, a class of substances that have been
      shown to exhibit chemopreventive and chemotherapeutic activities. In the present
      study the effects of resveratrol (100 and 200 microM), a phytoalexin found in
      grapes, and of the ethanolic extract of propolis (50 and 100 microg/ml), a
      natural honeybee hive product, were tested in androgen-resistant prostate cancer
      cells (DU145), a cell line resembling the last stage of prostate carcinoma. A
      comparison between the activity of these micronutrients and vinorelbine
      bitartrate (Navelbine), a semi-synthetic drug normally used in the therapy of
      prostate cancer, was conducted. Several biochemical parameters were tested, such
      as cell viability (MTT assay), cell membrane integrity (lactate dehydrogenase
      release), cell redox status (nitric oxide formation, reactive oxygen species
      production, reduced glutathione levels), genomic DNA fragmentation (COMET assay)
      with special attention on the presence of apoptotic DNA damage (TUNEL test), and
      possible mitochondrial transmembrane potential alteration (deltapsi). Our results
      point out the anticancer activity of resveratrol and propolis extract in human
      prostate cancer, exerting their cytotoxicity through two different types of cell
      death: necrosis and apoptosis, respectively. The data obtained suggest the
      possible use of these micronutrients both in alternative to classic chemotherapy,
      and in combination with very low dosage of vinorelbine (5 microM).

PMID- 15490974
TI  - Modulation of Wnt-specific colon cancer cell kill by butyrate and lithium.
AB  - Colorectal cancer (CRC) may be particularly amenable to gene therapy because CRCs
      exhibit constitutive upregulation of Wnt signaling. We have previously
      demonstrated that butyrate, found in the colonic lumen, modulates Wnt signaling
      and nonspecifically upregulates transcription from minimal promoters. Because
      both of these actions may influence the efficiency and specificity of Wnt
      targeted expression, the effects of butyrate on Wnt-targeted gene therapy were
      determined. Lithium is another agent known to upregulate Wnt activity in HCT-116
      CRC cells and therefore may induce Wnt-targeted CRC cell kill. CRC cells were
      cotransfected with an expression vector for green fluorescent protein (GFP) and
      different versions of vectors coupling Wnt-sensitive promoters to FADD or
      diphtheria toxin A-chain (DT) effector genes. Cells were treated with butyrate
      and/or lithium chloride and flow cytometry was used to determine the percentage
      of remaining transfected (GFP-positive) cells. We demonstrate that promoter and
      cell type-specific differences occur in Wnt-specific cell kill induced by FADD
      and DT. A Wnt-sensitive version of the CMV promoter (TcfCMV) exhibited the
      optimum combination of efficient SW620 CRC cell kill and Wnt specificity; in
      addition, treatment with a physiologically relevant concentration of butyrate
      enhanced cell kill induced by TcfCMV-FADD while maintaining specificity. In HCT
      116 CRC cells, optimum results were achieved utilizing TcfFos-DT constructs and
      cotreatment with both butyrate and lithium. The findings suggest that effective
      CRC cell kill can be achieved by gene therapy through modulation of Wnt signaling
      by butyrate and/or lithium.

PMID- 15490975
TI  - Cell-free DNA and RNA in plasma as a new molecular marker for prostate cancer.
AB  - Extracellular nucleic acids could serve as molecular markers in the early
      detection of cancer and in the prediction of disease outcome. In this study we
      examined six molecular markers, such as: variations in the quantity of DNA in
      plasma, glutathione-S-transferase P1 (GSTP1) gene methylation status in plasma,
      carcinoembryonic antigen (CEA) and prostate-specific membrane antigen (PSMA) mRNA
      in peripheral blood mononuclear cells (PBMC), and plasma samples from prostate
      cancer patients in different stages. The combination of DNA load and GSTP1
      promoter methylation status identified 83% (10/12) of the prostate cancer
      patients before therapy. This study shows that free circulating DNA can be
      detected in patients with prostate cancer compared with disease-free individuals,
      and suggests a new, noninvasive approach for early detection of prostate cancer.

PMID- 15490976
TI  - Radiosensitization of colon cancer cell lines by docetaxel: mechanisms of action.
AB  - The radiation-modifying action of docetaxel in experimental systems is well
      established. Docetaxel is also an increasingly important drug for the treatment
      of cancer in concurrent radiotherapy protocols. However, the mechanisms of
      docetaxel radiosensitization are not fully understood. We have investigated the
      magnitude and mechanisms of docetaxel radiosensitization in vitro in four human
      colorectal cancer cell lines (SW480, SW707, SW48, and HT29) with widely differing
      radiosensitivities. Cell survival curves were generated for a range of docetaxel
      concentrations (5-20 nM) alone and for X-rays (1-5 Gy) +/- 10 or 20 nM docetaxel
      (for 24 h before irradiation). Cell cycle distributions and apoptotic frequencies
      were measured during the treatments. Sensitivity to docetaxel alone was similar
      in all cell lines and could be attributed to massive induction of apoptosis (60
      80% by 24 h). Radiosensitivity varied widely; the surviving fractions at 2 Gy in
      the most resistant (HT29) and most sensitive (SW28) lines were 0.81 and 0.13,
      respectively. Exposure to 10 nM docetaxel induced a progressive accumulation of
      SW480, SW707, and SW48 cells in G2/M. After 24 h, 55-70% of the cells were in
      G2/M. It is likely, therefore, that accumulation in this radiosensitive phase of
      the cell cycle contributes significantly to radiosensitization by the drug.

PMID- 15490978
TI  - The changing face of peritonitis.

PMID- 15490977
TI  - PEG prodrugs of 6-mercaptopurine for parenteral administration using benzyl
      elimination of thiols.
AB  - 6-Mercaptopurine (6-MP) is an orally administered, water-insoluble purine analog
      that is effective against acute lymphatic leukemia. Oral absorption of 6-MP,
      however, is quite erratic, with only 16-50% of the administered dose reaching the
      blood. In this report, water-soluble parenterally administered poly(ethylene
      glycol) (PEG) prodrugs of 6-MP were synthesized using several chemical approaches
      that enabled the protection of the thiol group through a modification of the
      benzyl elimination (BE) system. In our earlier work on antimetabolites, it was
      found that branching of the PEG allowed greater loading of the active drug. This
      approach was also utilized within this work to give multiloaded systems. The
      resulting conjugates were stable in pH 7.4 PBS buffer as well as in rat plasma
      for extended periods. However, these conjugates did act as prodrugs in vivo and a
      number of PEG-6-MP constructs had significant (P < 0.05) activity in murine
      leukemia, as well as certain solid tumors, compared with unconjugated 6-MP in a
      solubilizing vehicle. The fact that some PEG-6-MP conjugates were stable during
      in vitro plasma dissociation assays, but demonstrated in vivo anticancer
      activity, suggests extravascular cleavage of the linking group. This work
      demonstrates that PEG conjugation is an effective means of solubilizing 6-MP for
      parenteral administration.

PMID- 15490979
TI  - Empirical treatment of CAPD peritonitis: to each his own?

PMID- 15490980
TI  - The law of diminishing returns: it is not always ultrafiltration failure.

PMID- 15490981
TI  - Changes in causative organisms and their antimicrobial susceptibilities in CAPD
      peritonitis: a single center's experience over one decade.
AB  - BACKGROUND: In recent years, the rate of peritonitis during continuous ambulatory
      peritoneal dialysis (CAPD) has been significantly reduced. However, peritonitis
      remains a major complication of CAPD, accounting for considerable mortality and
      hospitalization among CAPD patients. OBJECTIVE: To generate a "center tailored"
      treatment protocol for CAPD peritonitis by examining the changes of causative
      organisms and their susceptibilities to antimicrobial agents over the past 10
      years. METHOD: Retrospective review of the medical records of 1015 CAPD patients
      (1108 episodes of peritonitis) who were followed up from 1992 through 2001.
      RESULTS: The overall incidence of peritonitis was 0.40 episodes/patient-year. The
      annual rate of peritonitis and the incidence of peritonitis caused by a single
      gram-positive organism were significantly higher in 1992 and 1993 compared with
      those in the rest of the years (p < 0.05). The incidence of peritonitis due to
      coagulase-negative staphylococcus (CoNS) decreased significantly over time,
      whereas there was no significant change in the incidence of Staphylococcus aureus
      (SA)-induced peritonitis. Among CoNS, resistance to methicillin increased from
      18.4% in 1992-1993 to 41.7% in 2000-2001 (p < 0.05). In contrast, the incidence
      of methicillin-resistant SA was not different according to the calendar year.
      Catheter removal rates were significantly higher in peritonitis due to a single
      gram-negative organism (16.6%) compared with gram-positive peritonitis (4.8%, p <
      0.005). The mortality associated with peritonitis was also higher in gram
      negative (3.7%) compared with gram-positive peritonitis (1.4%), but there was no
      statistical significance. Among single gram-positive organism-induced
      peritonitis, catheter removal rates were significantly higher in SA (9.3%) than
      those in CoNS (2.9%, p < 0.01) and other gram-positive organisms (2.9%, p <
      0.05). In peritonitis caused by CoNS, the methicillin-resistant group showed
      significantly higher removal rates than the methicillin-susceptible group (8.2%
      vs 1.0%, p < 0.01). CONCLUSION: The incidence of peritonitis for 2001 decreased
      to less than half that for 1992, due mainly to a significant decrease in CoNS
      induced peritonitis, whereas the proportions of peritonitis due to a single gram
      negative organism and methicillin-resistant CoNS increased. These findings
      suggest that it is necessary to prepare new center-based guidelines for the
      initial empirical treatment of CAPD peritonitis.

PMID- 15490982
TI  - Vancomycin and ciprofloxacin: systemic antibiotic administration for peritoneal
      dialysis-associated peritonitis.
AB  - OBJECTIVES: Peritonitis due to peritoneal dialysis (PD) is best treated
      empirically while waiting for the results of the dialysate culture. Thus,
      antibiotic therapy must cover both gram-positive and gram-negative micro
      organisms. First, over a period of 9 years in a multicenter study we evaluated
      the efficiency of a vancomycin and ciprofloxacin combination given as the first
      line treatment protocol for PD peritonitis. Second, we evaluated whether a
      systemic route of administration of the antibiotics could be an interesting
      alternative to the usual cumbersome intraperitoneal drug administration. METHODS:
      Vancomycin 15 mg/kg body weight, intravenous, and oral ciprofloxacin 250 mg two
      times per day (500 mg twice per day if residual creatinine clearance was above 3
      mL/minute) were prescribed at diagnosis of peritonitis. Vancomycin injections
      were repeated (when blood trough level was expected to be below 12 microg/mL) in
      cases of gram-positive organisms for a total duration of 3 weeks. Ciprofloxacin
      was given for a total of 3 weeks in cases of gram-negative and a total of 10 days
      for susceptible gram-positive infections. RESULTS: A total of 129 episodes of
      peritonitis occurred; 28 of them were not included in the study because of
      protocol violation (n = 15) or fungal (n = 7) or fecal (n = 6) peritonitis,
      leaving 101 peritonitis episodes for analysis. 52 (51.5%) gram-positive and 28
      (27.7%) gram-negative organisms were grown; 38 gram-positive organisms were
      coagulase-negative staphylococci. No organism was identified in 8 peritonitis
      episodes, whereas 13 peritonitis episodes were caused by more than 1 organism.
      35% of the coagulase-negative staphylococci were resistant to first-generation
      cephalosporin and methicillin, whereas all were susceptible to vancomycin. For
      gram-negative bacilli, the susceptibility rate was 96% and 95% for ciprofloxacin
      and ceftazidime respectively. The overall treatment success rate was 77.2% (78 of
      the 101 peritonitis episodes): 61.4% at first intention and 15.8% after
      optimization of the antibiotic therapy (second intention). The protocol failed in
      22.8% of the peritonitis episodes. Hospitalization was required in 52% of the
      peritonitis episodes; average hospitalization was 11 (range 1-45) days.
      CONCLUSION: Systemic vancomycin and ciprofloxacin administration is a simple and
      efficient first-line protocol antibiotic therapy for PD peritonitis. In our
      opinion, vancomycin should still be used for gram-positive infections because of
      its high susceptibility rate compared with first-generation cephalosporins,
      providing a close monitoring of the local epidemiology. Oral ciprofloxacin
      provides satisfactory results in gram-negative infections, comparable to those
      obtained with intraperitoneal ceftazidime or aminoglycosides.

PMID- 15490983
TI  - Cefazolin plus ceftazidime versus imipenem/cilastatin monotherapy for treatment
      of CAPD peritonitis--a randomized controlled trial.
AB  - BACKGROUND: Peritonitis is a serious complication of peritoneal dialysis (PD). We
      studied the efficacy of imipenem/cilastatin monotherapy in the treatment of PD
      related peritonitis. METHODS: We performed an open-label, randomized control
      study comparing imipenem/cilastatin monotherapy (treatment group) versus
      cefazolin plus ceftazidime (control group) in the treatment of PD peritonitis.
      The result was further compared to a historic group treated with cefazolin plus
      netilmycin. Outcome measures were primary response rate at day 10 and complete
      cure rate. RESULTS: We enrolled 51 patients in the treatment group, 51 in the
      control group, and identified 96 in the historic group. The primary response rate
      to the assigned antibiotics was 49.0%, 51.0%, and 49.0% for the treatment,
      control, and historic groups, respectively (p = 0.97). The primary response rate
      allowing for change in antibiotic was 82.4%, 90.2%, and 82.3%, respectively, for
      the three groups (p = 0.41). The complete cure rate was 72.5%, 80.4%, and 82.3%,
      respectively (p = 0.60). Tenckhoff catheter removal was needed in 6 cases in the
      treatment group, 6 cases in the control group, and 13 cases in the historic group
      (p = 0.90). CONCLUSIONS: We concluded that monotherapy of imipenem/cilastatin has
      similar efficacy compared to the two standard regimens of cefazolin plus
      ceftazidime or netilmycin in the treatment of PD peritonitis.

PMID- 15490984
TI  - Pharmacokinetics of oral ciprofloxacin in continuous cycling peritoneal dialysis.
AB  - BACKGROUND: In order to avoid aminoglycosides, the International Society for
      Peritoneal Dialysis recommends cefazolin and ceftazidime for empirical treatment
      of peritonitis. Ciprofloxacin covers relevant gram-negative pathogens without the
      resistance associated with ceftazidime. However, ciprofloxacin pharmacokinetic
      data in patients on continuous cycling peritoneal dialysis (CCPD) are lacking.
      OBJECTIVES: (1) To determine the pharmacokinetics of oral ciprofloxacin in CCPD
      patients, (2) to compare serum and dialysate ciprofloxacin concentrations with
      minimum inhibitory concentrations (MIC) of the gram-negative bacteria associated
      with peritonitis, and (3) to establish oral ciprofloxacin dosing guidelines for
      the empirical treatment of peritonitis in patients receiving CCPD. METHODS:
      Eligible CCPD patients received 2 doses of ciprofloxacin: 750 mg orally every 12
      hours. Serial blood and end-of-dwell dialysate samples were collected during the
      first 12-hour interval; an end-of-dwell dialysate sample from the overnight dwell
      and a final blood sample were collected at the end of the second 12-hour
      interval. Ciprofloxacin concentrations were determined using a liquid
      chromatographic (HPLC)-fluorescence method. Pharmacokinetic calculations were
      completed assuming a one-compartment model. RESULTS: Eight patients completed the
      study. The pharmacokinetic parameters determined for ciprofloxacin were (mean +/-
      SEM) serum half-life 10.1 +/- 1.2 hours, maximum serum concentration 2.7 +/- 0.5
      mg/L, time to maximum serum concentration 1.6 +/- 0.1 hours after the first dose,
      and peritoneal clearance 1.2% +/- 0.1% of the mean calculated total body
      clearance. While all patients achieved serum area under the concentration-time
      curve:MIC > 125 for Escherichia coli and Klebsiella species after the first dose,
      only 2 patients achieved this goal for Pseudomonas aeruginosa. End-of-dwell
      dialysate concentrations were above the MIC for E. coli, Klebsiella spp, and P.
      aeruginosa after the second dose. CONCLUSION: Ciprofloxacin 750 mg orally every
      12 hours in CCPD patients may be useful for empirical gram-negative coverage of
      CCPD peritonitis and for treatment of documented peritonitis caused by sensitive
      E. coli or Klebsiella species. While ceftazidime may be required for documented
      pseudomonal peritonitis, the oral ciprofloxacin regimen achieved adequate serum
      concentrations to treat systemic gram-negative infections caused by sensitive E.
      coli or Klebsiella species.

PMID- 15490985
TI  - Exit-site infections by non-diphtheria corynebacteria in CAPD.
AB  - Non-diphtheria corynebacteria species cause disease in risk populations such as
      immunocompromised patients and patients with indwelling medical devices. Despite
      reports of exit-site infection and peritonitis caused by non-diphtheria
      corynebacteria, these organisms are frequently dismissed as contaminants. During
      a 10-year observation period, we prospectively identified 8 cases of exit
      site/tunnel infections caused by 2 different species of corynebacteria
      (Corynebacterium striatum in 5 and C. jeikeium in 3 cases). Four patients
      experienced a second episode of exit-site infection 3 months (2 cases), 25
      months, and 40 months, respectively, after termination of an oral cephalosporin
      therapy of 4 to 6 weeks' duration. Non-diphtheria corynebacteria accounted for 9%
      of all exit-site infections during the study period. All catheter-related
      infections healed; no catheter had to be removed. The diagnosis of catheter
      related non-diphtheria corynebacteria infection may be suspected when Gram stain
      shows gram-positive rods and with colony morphology and commercial biochemical
      identification systems. Susceptibility of non-diphtheria corynebacteria to
      antibiotics may vary, especially in C. jeikeium. Virtually all Corynebacterium
      species are sensitive to vancomycin. Empirical antibiotic therapy with vancomycin
      should be initiated while antibiotic susceptibility testing is being carried out.
      Oral cephalosporin may be an alternative treatment regimen for exit-site
      infections if sensitive. This study highlights the importance of non-diphtheria
      corynebacteria as emerging nosocomial pathogens in the population of end-stage
      renal disease patients on on continuous ambulatory peritoneal dialysis.

PMID- 15490986
TI  - A comparison of peritoneal equilibration tests performed 1 and 4 weeks after PD
      commencement.
AB  - OBJECTIVE: The aim of this study was to prospectively evaluate the ability of a
      peritoneal equilibration test (PET) performed in the first week of peritoneal
      dialysis (PD) to predict subsequent transport status, as determined by a PET at 4
      weeks and >1 year after PD commencement. DESIGN: Prospective observational study
      of an incident PD cohort at a single center. SETTING: Tertiary-care institutional
      dialysis center. PARTICIPANTS: The study included 50 consecutive patients
      commencing PD at the Princess Alexandra Hospital between 25/2/2001 and 14/5/2003
      (mean age 60.9 +/- 12.2 years, 54% male, 92% Caucasian, 38% diabetic). All
      patients were initially prescribed continuous ambulatory PD. MAIN MEASUREMENTS:
      Measurements performed during paired PETs included dialysate-to-plasma ratios of
      urea (D/P urea) and creatinine (D/P creatinine) at 4 hours, the ratio of
      dialysate glucose concentrations at 0 and 4 hours (D/D0 glucose), and drain
      volumes at 4 hours. RESULTS: When paired 1-week and 1-month PET data were
      analyzed, significant changes were observed in measured D/P urea (0.91 +/- 0.07
      vs 0.94 +/- 0.07 respectively; p < 0.05), D/P creatinine (0.55 +/- 0.12 vs 0.66
      +/- 0.11, p < 0.001), and D/D0 glucose (0.38 +/- 0.08 vs 0.36 +/- 0.10, p <
      0.05). Using Bland-Altman analysis, the repeatability coefficients were 0.17,
      0.20, and 0.13, respectively. Agreement between 1-week and 1-month PET
      measurements with respect to peritoneal transport category was moderate for D/D0
      glucose (weighted kappa 0.52), but poor for D/P urea (0.30), D/P creatinine
      (0.35), and drain volumes (0.20). The PET measurements performed more than 1 year
      following PD commencement (n = 28) generally agreed closely with 1-month
      measurements, and poorly with 1-week measurements. CONCLUSIONS: Peritoneal
      transport characteristics change significantly within the first month of PD. PETs
      carried out during this time should be considered preliminary and should be
      confirmed by a PET 4 weeks later. Nevertheless, performing an early D/D0 glucose
      measurement at 1 week predicted ultimate transport status sufficiently well to
      facilitate early clinical decision-making about optimal PD modality while
      patients were still receiving PD training. On the other hand, the widespread
      practice of using measured drain volumes in the first week to predict ultimate
      transport category is highly inaccurate and not recommended.

PMID- 15490987
TI  - Retroperitoneal leakage as a cause of ultrafiltration failure.
AB  - We report 3 patients on continuous ambulatory peritoneal dialysis (CAPD) who
      developed reversible ultrafiltration failure secondary to retroperitoneal
      leakage. The patients presented with pulmonary edema and fluid overload following
      a sudden onset of ultrafiltration failure on maintenance CAPD. There was no
      localized edema, suggesting peritoneal leakage in the abdominal wall or the
      perineum. Radiological examination showed no migration of the Tenckhoff catheter.
      Leakage of dialysate into the retroperitoneal space was only revealed by computed
      tomographic (CT) peritoneography. These patients were then treated with
      intermittent peritoneal dialysis twice weekly. After repeated CT peritoneography
      showing complete resolution of the leakage, they successfully resumed CAPD
      treatment 2 months later, without ultrafiltration problems. Our finding suggests
      that retroperitoneal leakage could be one of the uncommon, yet reversible, causes
      of acute ultrafiltration failure that can be diagnosed with CT peritoneography.

PMID- 15490989
TI  - Bleeding complications associated with peritoneal dialysis catheter insertion.
AB  - OBJECTIVE: To identify the incidence of bleeding complications associated with
      peritoneal dialysis catheter insertion. DESIGN: Retrospective review at a
      tertiary-care center of all double-cuffed Tenckhoff catheters placed surgically
      from 1 January 1992 to 1 October 2003 to identify the incidence of major bleeding
      complications occurring with catheter insertion. Major bleeding episodes were
      defined as > or = 3% decline in hematocrit, or the need for surgical intervention
      or blood transfusion within 2 weeks of insertion. RESULTS: 292 catheters had been
      inserted in 263 patients. Six patients satisfied the criteria for a major
      bleeding event, for a major bleeding complication rate of 2%. Bleeding was
      associated with perioperative anticoagulation in 3 patients, uremia and
      thrombocytopenia in 1 patient, aspirin use and thrombocytopenia in 1 patient, and
      1 patient experienced intraoperative bleeding. Coagulation parameters were not
      obtained prior to the procedure in 2 of the 6 patients. CONCLUSION: The rate of
      serious bleeding complications related to catheter insertion is low and usually
      associated with anticoagulation. Holding anticoagulation therapy for a minimum of
      24 hours during the postoperative period should eliminate much of the risk.
      Coagulation parameters should also be obtained and corrected preoperatively.

PMID- 15490988
TI  - Ossification of the peritoneal membrane.
AB  - BACKGROUND: Peritoneal dialysis (PD) patients rarely develop sclerosing
      peritonitis (SP), a severe, life-threatening condition of unknown pathogenesis.
      Ossification of the peritoneum (PO) is a rare occurrence, which has, however,
      been reported in PD patients with SP. OBJECTIVE: To investigate etiopathogenetic
      correlations between PO and SP by histopathological examination. METHOD: We
      examined biopsy specimens, obtained by laparoscopy or during surgery from 36
      patients with SP, from all parts of Italy in the past 8 years for evidence of
      peritoneal calcification or ossification. Other studies were performed on a
      sample of dense white material found under the parietal peritoneum of 1 patient
      during laparoscopy. RESULTS: Ossification of the peritoneum was found in 4/16
      patients with calcifications. In addition to PO, we also found bone marrow in two
      specimens and arterial ossification in one case. In specimens with
      calcifications, and especially those with ossification, there was evidence of
      peritoneal inflammation with infiltration of lymphocytes, multinuclear giant
      cells, macrophages, and mast cells. The chemical composition of the whitish
      material was 85% calcium chloride and 15% hydroxyapatite. CONCLUSIONS:
      Calcifications alone were found in 33% (12/36) of cases of SP; 11% of SP cases
      were complicated by both peritoneal calcification and ossification (4/36), which
      indicates great availability of calcium under conditions of inflammation. Where
      does this calcium come from? In 1 patient with PO, the quantity of calcium was
      enormous and its unusual composition suggested a link with the calcium contained
      in dialysis solution.

PMID- 15490990
TI  - Chronic peritoneal dialysis catheters in children: a fifteen-year experience of
      the Italian Registry of Pediatric Chronic Peritoneal Dialysis.
AB  - OBJECTIVE: To analyze data on 503 chronic peritoneal dialysis (CPD) catheters
      implanted between 1986 and 2000 in pediatric patients enrolled in the Italian
      Registry of Pediatric Chronic Peritoneal Dialysis (the Registry), comparing three
      different time periods: 1986-1990, 1991-1995, and 1996-2000. DESIGN:
      Retrospective study. SETTING: 23 dialysis centers participating in the Registry.
      METHODS: Data were collected from questionnaires filled in every year. The
      information for each peritoneal catheter included type, site and technique of
      insertion, exit-site orientation, exit-site care, complications, survival, and
      reason for removal. PATIENTS: 503 catheters were implanted in 363 pediatric
      patients aged younger than 15 years at the start of CPD: 97 catheters in patients
      under 2 years of age, 67 in patients aged 2-5 years, and 339 in patients over 5
      years of age. Mean patient age at onset of CPD was 8.0 +/- 5.1 years. All
      catheters were surgically implanted and omentectomy was performed in 82.4% of
      cases. The catheters used were Tenckhoff [468 (93.0%): 443 double cuff, 25 single
      cuff] and double-cuffed Valli [35 (7.0%)]. The entry site was in the midline in
      153 cases (30.4%) and paramedian in 350 (69.6%). RESULTS: During 9048 dialysis
      months we observed 451 catheter-related complications, yielding an incidence of 1
      episode/20.1 CPD-months: 330 catheter infections (exit-site and/or tunnel
      infections), 26 leakages, 26 dislocations, 24 obstructions, 22 cuff extrusions, 6
      hemoperitoneums, 17 others. 171 catheters were removed due to catheter-related
      causes; exit-site and/or tunnel infections were the main cause for removal
      (75.4%), followed by obstruction, dislocation, outer-cuff extrusion, and leakage.
      Younger children (< 2 years) had a higher risk of infectious causes of catheter
      removal compared to children aged 2-5 years (p = 0.004) and over 5 years of age
      (p = 0.002). During the 15-year observation period, a significant reduction in
      the incidence of leakage was observed and risk of leakage was lower in catheters
      with paramedian entry site compared to catheters with midline entry site. Removal
      and replacement of peritoneal catheters during the same surgical operation was
      performed in 76.3% of catheter removals. Catheter survival rate was 78.1% at 12
      months, 58.5% at 24 months, 43.8% at 36 months, and 34.6% at 48 months. No
      difference in catheter survival was observed in younger children (< 2 years)
      compared with the two other age groups: < 2 years versus 2-5 years hazard ratio
      0.7, 95% confidence interval (95%CI) 0.4-1.2; < 2 years versus > 5 years hazard
      ratio 0.8, 95%CI 0.5-1.1. CONCLUSIONS: In this survey, we observed better
      catheter survival in comparison with data reported by the Registry in 1998.
      Catheter survival improved especially in younger children (< 2 years), a group
      that previously had a decreased catheter survival rate compared to older age
      groups. In addition to the progressive increase in experience acquired by
      dialysis centers, this upward trend may also be related to greater use of double
      cuffed catheters, with paramedian exit site, and a higher frequency of
      omentectomy.

PMID- 15490991
TI  - Ciprofloxacin as adjunctive agent in treating cryptococcal peritonitis.

PMID- 15490992
TI  - Bacillus circulans peritonitis in a patient treated with CAPD.

PMID- 15490993
TI  - Pregnant doctors need better working conditions.

PMID- 15490994
TI  - Infant feeding: factors affecting initiation, exclusivity and duration.
AB  - The study objective was to determine the initiation rate, duration and
      exclusiveness of breastfeeding, in women resident in the North Eastern Health
      Board (NEHB) region. An additional aim was to identify determinants that
      influence the initiation and duration of all types of breastfeeding. All eligible
      mothers completed a self-administered questionnaire. For breastfeeding mothers
      there was additional follow-up, by telephone, at six and fourteen weeks
      postnatal. In total, 127 (51.4%) mothers initiated breastfeeding. This gradually
      declined to 52 (21.1%) at 14 weeks postnatal. Mothers' attributes significantly
      associated with initiating breastfeeding included: having previously breastfed,
      completed third level education, decision to breastfeed made early in pregnancy,
      being a non-smoker, having a mother who also breastfed, belonging to higher
      social class and age 24 years or older. However, after controlling for all of
      these variables in a regression model, only the following factors remained
      significant: having previously breastfed, completed third level education and the
      decision to breastfeed made early in pregnancy. Therefore, as decisions on infant
      feeding method are made prior to or early in pregnancy, efforts to increase
      breastfeeding rates will have to occur at societal level. Health sector
      initiatives can only have limited effect. In addition, creative methods must be
      developed and employed to encourage women from lower socio-economic groups to
      breastfeed.

PMID- 15490995
TI  - Population based study of the cost of inpatient care for HIV-lnfected individuals
      in an Irish teaching hospital.
AB  - A microcosting evaluation of the cost of inpatient care of 69 HIV-infected
      patients in an Irish teaching hospital was conducted from the hospital
      perspective. The median cost per admission was 6220 Euros and median cost per
      inpatient day was 557 Euros. HIV related admissions were associated with a
      greater cost per admission than non-HIV related admissions. There was an inverse
      relationship between inpatient costs and CD4 count. Ward costs accounted for the
      majority of inpatient expenditure. This is the first detailed study of the cost
      of inpatient care for HIV-infected individuals in Ireland. This study provides
      the data necessary to estimate the burden of HIV disease in Ireland and to
      evaluate the cost-effectiveness of antiretroviral and other strategies to manage
      HIV infection in the Irish context.

PMID- 15490996
TI  - Work-related stress among paediatric non-consultant hospital doctors.
AB  - There have been many reports of Non-Consultant Hospital Doctors (NCHDs) deciding
      to leave hospital medicine in pursuit of a career with better hours and lifestyle
      such as general practice. It is not known, however, how widespread feelings of
      dissatisfaction are in paediatrics and whether work-related stress is a
      contributing factor. A postal survey of NCHDs in paediatric posts throughout the
      country was conducted in November 2000. Data collected included demographic and
      personal details. NCHDs were also asked their level of stress in relation to
      their daily work, patient-care, hospital environment and dealing with other staff
      members using an incremental scale from 1 to 5 (5 most stressed). 69% (71/103) of
      the questionnaires were returned. Equal numbers of males and females responded
      (48% vs 52%). 51% (36/71) of the NCHDs were registrars; 51% (36/71) were working
      within Dublin. More than three-quarters had graduated from a European Union (EU)
      medical school (77%, 55/71). While the majority (79%, 56/71) were either
      satisfied or very satisfied with paediatrics as their chosen specialty, 79%
      (56/71) admitted to work-related stress causing job dissatisfaction with 71%
      (50/71) having experienced 3 or more stressful situations in the previous week.
      56% (41/71) graded their occupational stress level at 4 or 5. Routine non-medical
      work and poor job prospects were the main factors causing job dissatisfaction.
      With regard to daily duties, the situations causing stress were acute emergency
      situations (51%, 36/71), being solely responsible for patients when on-call (52%,
      19/36) and making decisions after a night on-call (76%, 50/67). The general
      attitudes of nursing staff were stressful to 40% (28/71) with 39% (27/71) stating
      having a difference of opinion with a nurse at least once every week. Relating to
      consultants was moderately stressful to 26% (19/71) and very stressful to 4%
      (3/71). Uncomfortable sleeping quarters and having insufficient time for meals
      were noted to be at least moderately stressful (stress levels 3 to 5) for 70%
      (50/71) and 92% (65/71) respectively. 59% (42/71) felt that their social life was
      greatly affected by their work. 68% (48/71) have considered leaving paediatrics
      with almost half (48%, 23/48) considering this seriously or very seriously. More
      than half stated that their alternative career choice would be general practice
      (61%, 29/48). The results of our survey show that work-related stress is common
      among paediatric NCHDs and is associated mainly with long working hours, sub
      optimal on-call conditions, and dealing with very ill patients.

PMID- 15490997
TI  - Is there a relationship between the structure of Irish psychiatric
      multidisciplinary teams and patient outcome?
AB  - This study evaluated the structure of psychiatric multidisciplinary teams within
      eight Irish Health Boards over a two year period (1997 and 1998). Furthermore, it
      assessed the relationship between team structure and three measures of
      psychiatric outcome within individual Health Board areas. The findings suggest a
      significant variation between Health Boards in relation to the staffing of
      psychiatric multidisciplinary teams. Although there was no evidence that the
      structure of multidisciplinary teams influenced suicide rates or duration of
      hospitalization, it had a significant independent effect on admission rates to
      psychiatric units.

PMID- 15490998
TI  - Customer needs, expectations, and satisfaction with clinical neurophysiology
      services in Ireland: a case for tele-neurophysiology development.
AB  - Although equitable access to services should be based on need, geographical
      location of patients and their clinicians can give rise to inequalities in
      healthcare delivery. Development of tele-medicine services can improve equity of
      access. The specialty of Clinical Neurophysiology (CN), currently under-developed
      in Ireland provides an example of such potential. This study aimed to determine
      the needs, expectations, and satisfaction of CN customers, namely patients and
      referring clinicians. The goal was to examine geographical impediments to access
      that might be addressed by the introduction of tele-neurophysiology. Two customer
      surveys were conducted: CN referring clinicians and CN patients. Thirty-one North
      Western Health Board (NWHB) consultant clinicians responded to a postal survey.
      Distance and delays caused by long waiting lists were felt to deter or make CN
      referral irrelevant. Ninety-seven percent believed the lack of a local service
      negatively impacts on patient management and 93% would welcome the introduction
      of a tele-neurophysiology service. The geographical location of patient's
      residence and/or the location of the referring clinician's practice influenced
      waiting lists for CN. Fifty-eight (105/182) percent of patients living in a
      region with a CN service compared to 39% (50/128) of those living in a region
      with no service received an appointment within one month. In addition to the
      current insufficient CN service capacity in Ireland, these surveys highlighted
      geographical inequities. Tele-neurophysiology has the potential to speed-up
      diagnosis, result in more patients being appropriately investigated and be fairer
      to patients.

PMID- 15490999
TI  - Acute medical take or subacute-on-chronic medical take?
AB  - INTRODUCTION: Older people are a significant source of emergency admissions to
      general hospitals relative to their proportion of the population. Little is known
      of the acuity of these admissions, aspects of which this study aims to determine.
      METHODOLOGY: A prospective survey of 1 in 10 acute general takes in a university
      teaching hospital over 11 months. Age, sex, acuity of presentation, premorbid
      functional status and cognitive impairment were recorded. RESULTS: Of 332
      admissions, 127 (38%) patients were aged 65 years or over and 205 under 65. Of >
      or =65's, 53 (42 ) presented <2 days of symptoms compared to 117 (57%) <65's.
      Mean delay between onset of primary symptom and presentation was 8.76 days (> or
      =65's) and 6.77 days (<65's). Previous functional loss was present in 42% of > or
      =65's. On admission, 36% of > or =65's were deemed cognitively impaired.
      CONCLUSION: Acute on chronic illness represents a significant proportion of
      'acute general take'. Older patients admitted in this fashion also tend to
      present to hospital later after the onset of their symptoms and with more
      physical and cognitive impairment than younger counterparts. These findings are
      supportive of the development of better models for managing chronic disease, such
      as acute geriatric medicine, stroke units, admission avoidance strategies and
      focussed community supports.

PMID- 15491000
TI  - Randomised controlled trials in Irish general practice.
AB  - There have been a limited number of randomised controlled trials carried out in
      Irish general practice. This paper presents an overview of the particular issues
      involved, based on a recently completed randomised controlled trial of diabetes
      shared care. Study design, ethical considerations, practice and patient related
      factors including recruitment and barriers to participation and the role of
      parallel economic and qualitative analyses are considered with a view to
      informing future study design.

PMID- 15491001
TI  - Early pregnancy loss: how do men feel?
AB  - One in five pregnancies (20%) end in miscarriage. A specialized early pregnancy
      loss clinic to provide dedicated medical advice and support was established at
      the Rotunda Hospital in July 2002. A qualitative pilot study was conducted in
      July 2002 to assess the emotional response of male partners and also to establish
      if sufficient support services are provided for them. Ten consecutive couples
      attending the clinic 6-8 weeks following early pregnancy loss were included in
      the study. The partners were asked to complete a questionnaire with open and
      closed questions and return in the envelope provided. Nine questionnaires were
      returned. The average age of men attended was 28.6 years (range 20-39). The
      feelings described by men were typical of the grief and bereavement process. All
      wanted more time for discussion with doctors. They felt marginalized and although
      they felt support services for their partner were adequate, they felt that more
      support services for male partners should be provided. Based on these research
      findings, the specialized early pregnancy loss clinic is being developed to
      partner's needs and expectations. The appointment letter sent to the women now
      specifically states that the partner is welcome to attend. Partners are now
      included in the consultation.

PMID- 15491002
TI  - Demographic profile of the elderly population in Dublin accident and emergency
      hospital catchment areas.

PMID- 15491003
TI  - Transpupillary thermotherapy--introduction.

PMID- 15491004
TI  - Transpupillary thermotherapy for age-related macular degeneration: principles and
      techniques.
AB  - Transpupillary thermotherapy (TTT) is a subthreshold, low irradiance, long
      exposure duration, large spot size, infrared diode laser protocol. Retinal
      temperature increases in TTT for choroidal neovascularization (CNV) are
      substantially lower than those in conventional short-pulse photocoagulation, but
      they are maintained for 60 seconds to achieve therapeutic results. Treatment
      power is adjusted for retinal lesion size, chorioretinal pigmentation, macular
      elevation and media clarity. TTT uses 810-nm diode laser infrared radiation,
      which has no significant retinal phototoxicity. A parfocal laser delivery system
      is required to assure uniformity of irradiance across large diameter treatment
      spots. Relative contraindications for TTT include dense subretinal hemorrhage,
      prior focal photocoagulation and serous RPE detachment. Adverse events are rare,
      and include decreased vision and retinal arteriole occlusion. Randomized,
      prospective multi-center trials are underway to compare the results of TTT for
      occult CNV in age-related macular degeneration to the natural history of the
      disorder. Imaging, electrophysiologic or thermometric techniques may ultimately
      provide intra-operative or post-operative monitoring to assure the adequacy of
      TTT for CNV, despite the absence of ophthalmoscopically visible lesions.

PMID- 15491005
TI  - Ophthalmoscopic contact lenses for transpupillary thermotherapy.
AB  - Ophthalmoscopic contact lenses for transpupillary thermotherapy (TTT) must
      provide effective visualization of retinal treatment sites and transmission of
      infrared diode laser radiation. Selection and proper use of retinal laser lenses
      requires knowledge of their lateral magnification, laser beam magnification
      factor, field of view and resolution. Optical performance is analyzed for
      Goldmann-type lenses and a series of inverted image lenses of differing
      magnification. Goldmann lenses have the highest resolution, but inverted image
      lenses of comparable magnification have 2.5 times or more their field of view.
      Inverted image lenses of similar magnification can differ in resolution. They
      require 2-4% more incident laser power to produce the same retinal irradiance as
      a Goldmann lens, but this difference is small in comparison to other clinical
      variables. Tilting an ophthalmoscopic contact lens up to 15 degrees causes little
      distortion in the circularity of the retinal spot formed by a laser beam or
      difference in retinal irradiance across the spot. Inverted image lenses produce
      higher anterior segment irradiances than Goldmann-type lenses, but anterior
      segment injuries are less likely in TTT than conventional visible light, short
      pulse retinal photocoagulation because of the comparatively low irradiances used
      in TTT and the decreased absorption of diode laser infrared radiation in ocular
      media and melanin.

PMID- 15491006
TI  - Transpupillary thermotherapy (TTT) of occult choroidal neovascularization: a
      retrospective, noncomparative case series of fifty-seven eyes.
AB  - PURPOSE: To evaluate the efficacy of transpupillary thermotherapy (TTT) for the
      treatment of occult choroidal neovascularization. METHODS: A retrospective,
      noncomparative case series of 57 eyes of 52 patients who presented with occult
      subfoveal CNV and were treated with TTT. RESULTS: 83% of eyes were either stable
      (+/- one line) or showed improvement in visual acuity. 83% of eyes showed
      stabilization of their exudative process after one TTT treatment as evidenced by
      resorption of subretinal and/or intraretinal exudate or hemorrhage. Nine percent
      of eyes developed classic CNV during the mean follow-up time of ten months.
      CONCLUSIONS: TTT appears to stabilize the exudative process in eyes with occult
      CNV. A prospective, sham-controlled, randomized study (TTT4CNV Clinical Trial) is
      currently underway to directly compare TTT to the natural history of occult CNV.

PMID- 15491007
TI  - Transpupillary thermotherapy (TTT) for age-related macular degeneration.
AB  - PURPOSE: To review the results of transpupillary thermotherapy (TTT) on choroidal
      neovascular membranes associated with age-related macular degeneration (AMD).
      MATERIALS AND METHODS: 35 eyes of 35 patients with AMD and choroidal
      neovascularization and exudation were treated with TTT and had fundus photographs
      and fluorescein angiography (FA) before and at least six months after TTT. 28
      eyes had predominantly occult lesions as seen on FA, while 7 demonstrated
      primarily classic lesions. All were treated with 650mw power or less using the
      810 nm diode laser (3000 micron spot, duration of 60 seconds). Visual acuity,
      lesion size, and amount of subretinal fluid were determined by results of
      examination and review of photographs and fluorescein angiograms. RESULTS: A 50%
      reduction in subretinal fluid was achieved in 67% of treated eyes overall, with
      stabilization of vision (less than three lines of visual acuity lost) in 86%.
      Complications from treatment were infrequent (9%) and involved hemorrhage noted
      in the region of treatment upon follow-up. CONCLUSION: TTT promotes resolution of
      subretinal fluid and appears to stabilize visual acuity in patients with
      exudative AMD.

PMID- 15491008
TI  - Efficacy of transpupillary thermotherapy (TTT) in the treatment of occult
      subfoveal choroidal neovascularization in age-related macular degeneration.
AB  - PURPOSE: To determine the efficacy of transpupillary thermotherapy (TTT) in the
      treatment of occult subfoveal choroidal neovascularization in patients with age
      related macular degeneration (ARMD). METHODS: We conducted a retrospective review
      of patients with ARMD treated with TTT from June, 1999 through July, 2000 at a
      retina referral practice. TTT was delivered through a slit-lamp using a modified
      diode laser at 810 nm wavelength and a spot size of 3 mm delivered at one
      location for a minimum of 60 seconds duration. Re-treatment was performed at 2
      month intervals if indicated. RESULTS: 81 eyes of 77 patients were included in
      the study. Vision improved greater than one line Snellen in 18 eyes (22%), vision
      was stable within one line Snellen in 38 (47%), and worsened greater than one
      line Snellen in 25 (31%). Patients had a mean follow-up of 9 months. The average
      number of treatments was 1.37 (range 1 to 4). Pretreatment vision was less than
      or equal to 20/200 in 54% of eyes. CONCLUSIONS: Transpupillary thermotherapy may
      stabilize visual acuity in a majority of patients with occult subfoveal choroidal
      neovascularization secondary to ARMD. Proof of therapeutic benefit is best
      determined by a randomized clinical trial that is currently underway (TTT4CNV).

PMID- 15491010
TI  - Transpupillary thermotherapy of occult CNV with no or minimally classic CNV in
      age-related macular degeneration.
AB  - Transpupillary thermotherapy (TTT) has been suggested as a putative treatment for
      choroidal neovascularization (CNV) in age-related macular degeneration (AMD).
      This prospective study comprised 66 consecutive patients referred for exudative
      AMD with predominantly occult subfoveal CNV. Based on fluorescein angiography,
      there were 38 cases with occult CNV only, and 28 eyes with minimally classic CNV
      as well. Visual acuity was determined using the logarithmic ETDRS chart. For TTT
      a diode laser (810nm) with a power of 800 mW or 500-600 mW for a 3.0 mm spot was
      used (duration 60 sec.). Follow-up included clinical examination with
      biomicroscopy and fluorescein angiography at 2-3 months and 6 months in all
      cases. In the entire case material (n = 66), the mean visual acuity was
      preoperatively 20/125 (47.4 letters) and postoperatively 20/160 (41.8 letters)
      yielding a decay of 5.6 letters ("one line"). Visual acuity improved in 8 cases
      (12.1%), deteriorated in 17 (25.8%), and remained stable in 74.2%. In purely
      occult CNV visual acuity remained stable in 81.6% as compared to 64.3% in occult
      & minimally classic CNV; the former subgroup lost on the average 3.6 letters, the
      latter 8.3 letters (close to "two lines") over 6 months. The proportion of eyes
      losing at least 15 letters was 13.2% in purely occult CNV versus 35.7% in the
      occult & minimally classic subgroup. In 39 of 66 cases (59.1%) fluorescein
      leakage regressed to staining only concomitant with absorption of subretinal
      fluid. Complications associated with deterioration of visual acuity (17 cases)
      included postoperative hemorrhage, increase of exudation on angiography, and
      progressive fibrosis. The results indicate that TTT stabilizes visual acuity
      concomitant with regression of exudation and resorption of subretinal fluid in
      the majority of cases with predominantly occult CNV Cases with occult CNV only
      seem to do better than those with minimally classic CNV as well. The safety and
      complication rate appear to be acceptable. A randomized controlled trial is in
      progress.

PMID- 15491009
TI  - Transpupillary thermotherapy of occult choroidal neovascularization in age
      related macular degeneration.
AB  - PURPOSE: To evaluate the efficacy of transpupillary thermotherapy (TTT) in
      management of occult subfoveal choroidal neovascularization (CNV) in exudative
      age-related macular degeneration (AMD). METHODS: Retrospective chart review of
      eyes that were treated with TTT and had at least 12 weeks of follow-up. Base-line
      and final ETDRS visual acuity and fluorescein angiography (FA) were compared.
      RESULTS: For the 48 eyes which met inclusion criteria, mean pre-operative visual
      acuity was 20/128 (range: 20/50-20/500). Average follow-up was 27 weeks (range:
      12 weeks-55 weeks). At 3 months after treatment, 12 eyes (25%) improved 2 lines
      or more, 18 eyes (37.5%) had no change or 1 line of visual improvement, and 18
      eyes (37.5%) worsened 1 or more lines. No significant adverse event was noted
      during treatment. Three eyes developed large submacular hemorrhage within 2
      months of treatment. Based on clinical examination and FA, 61% of the eyes
      appeared to have reduction of subretinal fluid compared to pre-operative
      evaluations. CONCLUSION: Visual acuity was stable or improved in 62.5% of eyes in
      our series and the treatment was well tolerated. Longer follow up and larger
      number of patients would be required to evaluate the ultimate benefit of TTT in
      management of occult CNV due to AMD.

PMID- 15491011
TI  - Optical coherence tomography of subfoveal choroidal neovascularization treated
      with transpupillary thermotherapy.
AB  - Transpupillary thermotherapy (TTT) has been proposed as a new treatment modality
      for choroidal neovascularization (CNV). Most studies conducted show decreased
      exudation due to CNV and reduction of subretinal elevation. Optical coherence
      tomography (OCT) shows a dynamic sequence of changes early after treatment.
      Within 1 hour after TTT, OCT shows increased retinal thickness and intraretinal
      fluid with retinal elevation. One week after treatment, OCT shows decreased
      subretinal and intraretinal fluid and diminished retinal elevation. OCT can be a
      valuable method to assess the early effect of TTT. A placebo-controlled, multi
      center trial (TTT4CNV) evaluating the long-term efficacy and visual implications
      of TTT in occult CNV is underway.

PMID- 15491012
TI  - Fluorescein and indocyanine green angiography after transpupillary thermotherapy
      of choroidal neovascularization. Early vascular changes.
AB  - Transpupillary thermotherapy (TTT) is currently being evaluated in clinical
      trials for the treatment of choroidal neovascularization (CNV). Preliminary
      results show that TTT achieves closure of CNV and reduction in subretinal
      exudation while preserving visual acuity. Fluorescein and indocyanine green
      angiography reveal increased leakage activity from CNV and collateral choroid
      within 1 hour after TTT and absence of dye leakage from CNV at 1 week after
      treatment. Optical coherence tomography confirms the angiographic findings. The
      early vascular changes after TTT of CNV are similar to those observed after PDT
      of CNV. Transpupillary thermotherapy and PDT might share common mechanisms of
      action. A placebo-controlled, multi-center trial (TTT4CNV) evaluating the long
      term efficacy and visual implications of TTT in occult CNV is underway.

PMID- 15491013
TI  - FAQs: breast pain and fibroadenosis.

PMID- 15491014
TI  - Emergency contraception in practice.

PMID- 15491015
TI  - Hypertension in pregnancy.
AB  - Formal assessment of the risk of pre-eclampsia should be made early in pregnancy
      and antenatal care planned accordingly. Recommendations will emerge by the end of
      this year in a consensus statement (PRECOG guidelines) prepared by clinicians and
      the lay organisation Action on Pre-eclampsia (APEC) www.apec.org.uk. Some
      hospitals complement clinical risk assessment with Doppler screening of uterine
      artery waveforms in mid-pregnancy. Severe pre-eclampsia often takes an explosive
      course, evolving over a period of hours. Recognition may, therefore, not be
      amenable to intermittent blood pressure recording and urine testing, but requires
      women reporting relevant symptoms and GPs being sensitive to the possible
      significance of complaints such as vomiting and epigastric pain. Severe
      hypertension demands urgent antihypertensive treatment in hospital. Magnesium
      sulphate now has an accepted role in the prevention of eclampsia. Possible
      prevention of pre-eclampsia by antioxidant therapy is the subject of a clinical
      trial. Low-dose aspirin has a modest but beneficial effect in high-risk women.
      Delivery remains the definitive treatment for pre-eclampsia, but there may be
      initial deterioration after birth, especially in the HELLP syndrome.

PMID- 15491016
TI  - The GP's role in pelvic chronic pain.

PMID- 15491017
TI  - Managing the subfertile couple.

PMID- 15491018
TI  - Managing osteoporosis.

PMID- 15491019
TI  - How to succeed in the MRCGP.

PMID- 15491021
TI  - Laser treatment for skin problems.
AB  - Lasers and related 'intense pulsed light' (IPL) devices are increasingly being
      used to treat people with skin conditions in NHS dermatology and plastic surgery
      units, private hospitals and clinics, and cosmetic salons. Typical targets for
      such treatments include conditions involving excessive blood vessels (e.g. port
      wine stains), pigment (e.g. tattoos), inflammatory lesions (e.g. psoriasis),
      scars, excess hair, tumours and wrinkles. This broad and expanding range of uses
      raises questions about the effectiveness, safety and appropriateness of laser and
      IPL treatment. Here we consider these and other key issues in the use of these
      techniques to treat patients with skin problems.

PMID- 15491022
TI  - Update on insulin analogues.
AB  - Four recombinant human insulin analogues are currently available in the UK. In
      reviewingthefirst of these, insulin lispro, in 1997, we concluded that "it has a
      more rapid onset, time to peak and shorter duration of action than soluble human
      insulin" but "does not appear to alter overall control (haemoglobin A1c levels)
      and it is not clear whether it reduces the occurrence of hypoglycaemia compared
      with soluble human insulin". Recombinant analogues marketed in the UK since then
      include another short-acting analogue, [symbol: see text]insulin aspart
      (NovoRapid--Novo Nordisk), and two longer-acting analogues, [symbol: see
      text]insulin glargine (Lantus--Aventis Pharma) and [symbol: see text]insulin
      detemir (Levemir--Novo Nordisk). In addition, there are two biphasic formulations
      that contain both a short-acting analogue and a longer-acting protamine
      suspension of that analogue: biphasic insulin lispro (Humalog Mix25, Humalog
      Mix50--Lilly) and biphasic [symbol: see text]insulin aspart (NovoMix 30--Novo
      Nordisk). Here we review insulin analogues and consider what advantages, if any,
      they offer over conventional human insulin preparations.

PMID- 15491023
TI  - The art and science of cancer nursing in the genomic era.

PMID- 15491024
TI  - The biology of cancer genetics.
AB  - OBJECTIVES: To review cancer biology and associated genetic change. DATA SOURCES:
      Professional journals, texts, monographs, and Internet websites. CONCLUSION:
      Several types of genetic damage occur in cancer cells: activation of
      protooncogenes into oncogenes that give cells an abnormal growth advantage;
      inactivation of tumor suppressor genes that would normally slow or stop abnormal
      cell growth; the bypass of genes that cause aberrant cells to die by apoptosis;
      the ability to establish vasculature, and the ability to override genes that
      regulate cell senescence. The end result of accumulated genetic errors is cells
      that can reproduce without restriction, invade local tissues, and ultimately,
      establish distant metastases. IMPLICATIONS FOR NURSING PRACTICE: Identification
      of the genetic changes in cancer cells and of the proteins that these changes
      affect promises to provide diagnostic and prognostic markers as well as molecular
      targets for therapeutic intervention. It is critical that nurses have a basic
      understanding of cell biology and genetics so they may better comprehend the
      unfolding changes in medicine to best serve patients and families.

PMID- 15491025
TI  - Clinical applications of genetics in sporadic cancers.
AB  - OBJECTIVES: To describe how genetic information shapes our understanding of
      carcinogenesis; how genetic information influences recommendations for cancer
      screening, prevention, diagnosis, and treatment; and how genetic information may
      affect the prognosis of patients with cancer and the monitoring of anticancer
      treatment. DATA SOURCES: Medical and nursing literature, textbooks, Internet
      websites. CONCLUSION: The Human Genome Project has taken oncology one step
      further toward accurate diagnosis and treatment of many forms of cancer. There
      are many genetic traits that can be associated with increased cancer risk,
      diagnosis, and selection of treatments. IMPLICATIONS FOR NURSING PRACTICE:
      Oncology nursing practice is directly affected by the developments of medical
      genetics. The information gained can be used by nurses at all stages of the
      cancer continuum when administering these new therapies.

PMID- 15491026
TI  - Common hereditary cancer syndromes.
AB  - OBJECTIVES: To review cancer risk assessment and counseling, hereditary cancer
      syndrome risk factors, indicators for cancer predisposition testing, and
      interpretation of genetic test results. DATA SOURCES: Research studies, review
      articles, and authors' experience. CONCLUSION: Approximately 10% of those with a
      diagnosis of cancer may have a hereditary predisposition. In many cases genetic
      testing for susceptibility genes may be available. Knowledge of the results of
      genetic testing can be helpful when developing a plan for cancer prevention and
      early detection, and addressing concerns associated with genetic testing with the
      individual and family. IMPLICATIONS FOR NURSING PRACTICE: Nurses need to know how
      to access genetic resources and to identify, evaluate, and care for patients and
      families at risk of or diagnosed with common hereditary cancer syndromes.

PMID- 15491027
TI  - Genetics and oncology nursing.
AB  - OBJECTIVES: To review oncology nursing practice in the genetic era, how genetic
      information is used across the cancer care continuum, practice guidelines, and
      opportunities for genetic nursing education. DATA SOURCES: Published articles.
      CONCLUSION: Genetic information in oncology health care is used not only to
      predict risk but to elucidate disease biology, explain individual variation in
      vulnerability to environmental carcinogens, diagnose and characterize
      malignancies, design treatment regimens specific to a cancer's genetic
      fingerprint, develop new, therapeutic modalities, and clarify modulators of drug
      metabolism, efficacy, and interactions. IMPLICATIONS FOR NURSING PRACTICE: With
      current and emerging genetic discoveries, all oncology nurses will use genetic
      information in their practice.

PMID- 15491028
TI  - Psychosocial aspects of genetic counseling and testing.
AB  - OBJECTIVES: To highlight areas where persons who undergo BRCA1/2 mutation testing
      may benefit from psychosocial or behavioral support and intervention. DATA
      SOURCES: Published scientific literature, cal, and research experiences.
      CONCLUSION: Key psychosocial areas that deserve attention by clinicians and
      researchers include: indeterminate or inconclusive test results, selection of
      risk management strategies in unaffected BRCA1/2 mutation carriers, and genetic
      testing in minority communities. IMPLICATIONS FOR NURSING PRACTICE: By addressing
      the psychosocial issues faced by patients undergoing genetic testing for cancer,
      nurses have the potential to maximize opportunities for prevention, early
      detection, and healthy coping.

PMID- 15491029
TI  - A model of survivorship in cancer genetic care.
AB  - OBJECTIVES: To propose a shift in the paradigm of survivorship in genetic cancer
      care. DATA SOURCES: Published articles and, studies. CONCLUSION: Previous models
      of survivorship are insufficient to address the evolving needs of patients and
      families with heritable cancers. The construction of a new model of survivorship
      is needed to address the unique concerns of individuals who have undergone
      hereditary cancer risk assessment and counseling. IMPLICATIONS FOR NURSING
      PRACTICE: Health care providers must be familiar with the recommendations for
      treatment, surveillance, and follow-up care for individuals and families with
      heritable cancers to maximize their quantity and quality of life.

PMID- 15491030
TI  - Legal and ethical issues in cancer genetics nursing.
AB  - OBJECTIVES: This article will set forth major interests at stake for patients
      considering predictive genetic testing, some legal bases for protecting patients,
      and general ethical principles that can guide cancer genetic nurses in their
      practice. DATA SOURCES: Review of health, ethical, and legal literature
      CONCLUSION: There are many potential interests at stake for patients considering
      genetic testing for susceptibility to cancer and a number of legal protections
      for patients against genetic discrimination. Nurses and physicians who offer
      genetic testing should be aware of applicable laws in their states, and remain
      cognizant of evolving ethical principles that can guide the practice IMPLICATIONS
      FOR NURSING PRACTICE: Ethical and legal questions surrounding genetic testing
      linger--particularly for nurses and physicians whose primary concern is the best
      interests of the patient.

PMID- 15491031
TI  - Genomics: offering hope for oncology care.

PMID- 15491032
TI  - High school math helps explain observations during 25-gauge vitrectomy surgery.

PMID- 15491033
TI  - Retinal toxicity of intravitreal ganciclovir in rabbit eyes following vitrectomy
      and insertion of silicone oil.
AB  - BACKGROUND: Although intravitreal ganciclovir dosages up to 500 microg have been
      demonstrated to be safe in some studies, other studies have shown toxic retinal
      effects in rabbit eyes without silicone oil at lower dosages. In current clinical
      practice, the same dosage of intravitreal antiviral agent is given regardless of
      whether there has been retinal detachment repair with silicone oil. We performed
      a study to investigate, in rabbit eyes following vitrectomy and silicone oil
      insertion, the retinal toxicity of serial intravitreal injections of ganciclovir,
      using dosages previously found not to produce significant toxic effects in
      nonvitrectomized eyes. METHODS: Twenty-eight eyes of 14 New Zealand pigmented
      rabbits underwent pars plana vitrectomy and silicone oil insertion. One eye of
      each animal received an intravitreal ganciclovir injection twice weekly for 2
      weeks. The other eye received 0.1 mL of normal saline as a control. Three dosages
      of ganciclovir (50, 100 or 200 microg/0.1 mL) were used in three groups of three
      to six animals. Scotopic electroretinography and histologic examination were
      performed 2 weeks postoperatively. RESULTS: No differences in scotopic b-wave
      threshold (p = 0.23, 0.78 and 0.50 for ganciclovir dosages of 50, 100 and 200
      microg/0.1 mL respectively, Mann-Whitney U test) or in light microscopy findings
      were noted between the treatment and control eyes at any dosage of ganciclovir.
      Surgical complications were observed in eight eyes; the data for these eyes were
      not used for analysis. INTERPRETATION: Ganciclovir dosages of up to 200
      microg/0.1 mL appear to be safe for serial intravitreal injection in rabbit eyes
      following vitrectomy and silicone oil insertion.

PMID- 15491034
TI  - Assessment of retinal hemodynamics with the Canon laser blood flowmeter after a
      single dose of 2% dorzolamide hydrochloride eyedrops.
AB  - BACKGROUND: Dorzolamide hydrochloride is a carbonic anhydrase inhibitor that
      reduces intraocular pressure (IOP) by decreasing the production of aqueous humour
      in the ciliary body. Theoretically, topical use of this agent has the potential
      to directly affect retinal vasculature through local induced acidosis. We
      performed a study to determine whether there are changes in retinal arteriole
      hemodynamics, as assessed with the Canon laser blood flowmeter, in healthy
      subjects following topical administration of dorzolamide. METHODS: We recruited
      17 healthy volunteers, nine men and eight women aged 25 to 55 years (mean 31.4
      [standard deviation (SD) 9.88] years). The inclusion criteria were Snellen visual
      acuity of 20/30 or better, normal anterior eye examination, IOP of 21 mm Hg or
      less, and a normal fundus appearance. One eye of each subject was randomly
      assigned to receive a drop of 2% dorzolamide. The contralateral eye of 10 of the
      subjects received a placebo drop (artificial tears). Before and 1 hour after drop
      administration, we obtained blood flow measurements from an inferotemporal
      arteriole approximately 1 disc diameter from the optic nerve head rim using the
      Canon laser blood flowmeter, model 100. The IOP was measured by means of Goldmann
      applanation tonometry before and 1 hour after drop administration. RESULTS: The
      mean IOP was significantly reduced in the dorzolamide-treated eyes, from 14.4 mm
      Hg (SD 2.94 mm Hg) to 11.7 mm Hg (SD 2.50 mm Hg) (p < 0.001). The IOP was also
      reduced in the placebo group (15.6 mm Hg [SD 3.41 mm Hg] vs. 14.6 mm Hg [SD 3.28
      mm Hg]), but the difference was not significant. There was no significant
      difference in mean arteriole diameter, mean blood velocity or mean blood flow
      after drug administration in the dorzolamide-treated eyes. INTERPRETATION: Our
      results indicate that a single topical application of dorzolamide in healthy
      subjects has no effect on retinal arteriole diameter, blood velocity or blood
      flow, as measured with the Canon laser blood flowmeter. Longer-term studies of
      retinal hemodynamics in patients with glaucoma are warranted as evolving
      treatments aim to improve ocular blood flow as well as reduce IOP.

PMID- 15491035
TI  - Contact diode laser transscleral cyclophotocoagulation for refractory glaucoma:
      comparison of two treatment protocols.
AB  - BACKGROUND: Diode laser transscleral cyclophotocoagulation has shown promising
      results in the treatment of refractory glaucoma. Treatment with a lower energy
      level per pulse and lower total energy is safer but may be less effective. We
      performed a study to evaluate the clinical effectiveness and safety of contact
      transscleral cyclophotocoagulation using two different protocols in the treatment
      of Chinese patients with refractory glaucoma. METHODS: Review of the records of
      129 patients with refractory glaucoma who underwent contact transscleral
      cyclophotocoagulation for the first time performed by two different surgeons. In
      group 1 (73 eyes) the output was 2.5 W and the exposure time 2 seconds; in group
      2 (56 eyes) the corresponding values were 2.0 W and 1.5 seconds. We recorded the
      number of antiglaucoma medications used, Snellen visual acuity, slit-lamp
      biomicroscopic findings, intraocular pressure (IOP) and findings on
      ophthalmoscopy with pupil dilation before and 1 day, 1 week, 1 month, 3 months
      and 6 months after treatment. RESULTS: The mean age of the patients was 56.4
      years (standard deviation [SD] 18.3 years) in group 1 and 53.5 (SD 18.0) years in
      group 2. The most frequent diagnoses were neovascular glaucoma secondary to
      proliferative diabetic retinopathy or central retinal vein occlusion, and
      glaucoma associated with penetrating keratoplasty. The mean number of laser pulse
      applications per patient was 27 (SD 5.1) (range 10-36) in group 1 and 55 (SD 6.1)
      (range 40-60) in group 2. One month after treatment, the mean reduction in IOP
      was 20.2 mm Hg (SD 14.2 mm Hg) in group 1 and 13.7 mm Hg (SD 15.8 mm Hg) in group
      2, a significant difference (p = 0.035). There was no difference between the two
      groups in the mean reduction in IOP at 6 months (19.1 mm Hg [SD 15.1 mm Hg] vs.
      14.2 mm Hg [SD 16.3 mm Hg]). The mean reduction in the number of antiglaucoma
      medications was 1.2 (SD 1.1) in group 1 and 0.6 (SD 1.0) in group 2 (p = 0.003).
      The incidence rates of transient hyphema in the anterior chamber (23.3% vs. 7.1%)
      and of transient exudate in the anterior chamber (8.2% vs. 0.0%) were
      significantly higher in group 1 than in group 2 (p < 0.005). INTERPRETATION: To
      achieve greater IOP reduction with diode laser transscleral
      cyclophotocoagulation, an increase in energy per pulse may be more effective than
      an increase in total applications.

PMID- 15491036
TI  - Identification of fixation location with retinal photography in macular
      degeneration.
AB  - BACKGROUND: Identification of fixation location is an integral part of low vision
      assessment and subsequent rehabilitation. We performed a study to determine
      whether retinal photography is able to identify fixation location in eyes with
      age-related macular degeneration (AMD). METHODS: In a prospective, observational
      case series, consecutive patients with AMD attending a low-vision clinic
      underwent monocular fixation attempts at a fixation target of a standard
      ophthalmic fundus camera. Inclusion criteria included AMD with documented macular
      disease, low vision in both eyes and best-corrected visual acuity of 20/50 to
      20/200 in the tested eye. Retinal photography was used to document retinal
      location of attempted fixation. Macular perimetry was used to confirm acceptable
      fixation maintenance behaviour. Outcome measures included acceptable fixation
      maintenance during retinal photography and retinal location of fixation pattern.
      RESULTS: Twenty-one patients (14 women and 7 men with an average age of 78 [range
      53 to 86] years) met the inclusion criteria. In nine cases both eyes met the
      study criteria, for a total of 30 eyes. Of the 30 eyes, 24 (80%) had acceptable
      fixation maintenance with retinal photography (p = 0.939). In 17 (71%) of the 24
      eyes the retinal fixation location was superior to the macular scar.
      INTERPRETATION: The results suggest that retinal photography may provide a
      reliable method to identify retinal location of fixation in eyes with AMD.

PMID- 15491037
TI  - Myopia and astigmatism in retinopathy of prematurity after treatment with
      cryotherapy or laser photocoagulation.
AB  - BACKGROUND: Visual outcome studies have shown that laser photocoagulation may
      result in more favourable clinical outcomes than cryotherapy in threshold
      retinopathy of prematurity (ROP). Comparative refractive outcome studies have
      shown that patients treated with laser photocoagulation have less myopia than
      those treated with cryotherapy. We carried out a study to determine whether a
      difference in visual outcome or refraction exists in patients with threshold ROP
      who have been treated with cryotherapy vs. laser photocoagulation. METHODS: A
      retrospective cohort study was conducted comparing treatment results after at
      least 3 years of follow-up in patients with threshold ROP treated with
      cryotherapy or laser photocoagulation at a tertiary care children's hospital.
      Visual acuity and refraction were the outcomes studied. Covariates measured were
      sex, gestational age and birth weight. Analysis was performed with both bivariate
      analysis and multivariate models. RESULTS: Seventy-one eyes of 37 patients with
      threshold ROP were included in the study. Thirty-seven eyes received cryotherapy,
      and 34 eyes received laser photocoagulation. The mean spherical equivalent
      refraction was significantly lower in the cryotherapy group than in the laser
      photocoagulation group (-9.21 dioptres vs. -1.80 dioptres, p = 0.001). Patients
      in the cryotherapy group were more likely than those in the laser
      photocoagulation group to have against-the-rule astigmatism (odds ratio 6.86, p =
      0.004). Laser photocoagulation did not significantly lower the frequency of an
      unfavourable visual outcome (visual acuity worse than 20/200) (p = 0.09).
      INTERPRETATION: Eyes with threshold ROP treated with laser photocoagulation were
      significantly less myopic and less likely to have against-the-rule astigmatism
      than those treated with cryotherapy.

PMID- 15491038
TI  - Ocular surface disorders and tear function changes in patients with chronic renal
      failure.
AB  - BACKGROUND: Ocular surface changes, mainly squamous metaplasia of the
      conjunctival epithelium and corneoconjunctival calcification of unknown etiology,
      may develop in patients with chronic renal failure undergoing hemodialysis. An
      association between squamous metaplasia and corneoconjunctival calcification has
      been suggested. The purpose of this study was to investigate the relation between
      ocular surface disorders and tear function changes in patients with chronic renal
      failure undergoing hemodialysis. METHODS: In this prospective case-control study,
      42 patients with chronic renal failure and 20 age- and sex-matched control
      subjects underwent full ophthalmologic examination, tear function tests
      (including Schirmer's test, tear film break-up time [BUT] test and rose bengal
      staining) and impression cytology to determine the degree of conjunctival
      squamous metaplasia. They also responded to a questionnaire regarding subjective
      ocular complaints. Corneoconjunctival calcification was graded on a scale of 0 to
      5 according to the system proposed by Porter and Crombie. Impression cytology
      samples were graded on scale of 0 to 3 according to the Nelson classification.
      The relation between ocular surface disorders and tear function changes was
      evaluated. RESULTS: Of the 42 patients, 12 (28%) had grade 0 calcification, 10
      (24%) had grade 1, 14 (33%) had grade 2, and 6 (14%) had grade 3 or higher. Four
      patients (10%) had grade 0 squamous metaplasia, 22 (52%) had grade 1, 12 (28%)
      had grade 2, and 4 (10%) had grade 3. The difference between the patient and
      control subjects in squamous metaplasia grades and corneoconjunctival
      calcification grades was statistically significant (p < 0.001 and p = 0.022
      respectively). Abnormal tear film BUT (p = 0.002) and abnormal rose bengal
      staining (p = 0.023) were significantly more frequent in the patient group than
      in the control group. The grade of conjunctival squamous metaplasia was
      correlated with abnormal rose bengal staining (tau = 0.79, p < 0.001) and with
      the existence of subjective ocular complaints (tau = 0.32, p = 0.026). There was
      no correlation between corneoconjunctival calcification and tear function
      changes. INTERPRETATION: Abnormal rose bengal staining and the presence of
      subjective ocular complaints may be used as follow-up criteria for ocular surface
      disorders in patients with chronic renal failure regularly undergoing
      hemodialysis.

PMID- 15491039
TI  - Identification of retained intracanalicular plugs with ultrasound biomicroscopy.
AB  - BACKGROUND: Punctal plugs may be associated with complications, the most common
      being secondary epiphora due to canalicular obstruction. Simple lacrimal
      irrigation will diagnose an obstruction within the canaliculus but will not
      determine whether the plug is still present at the site of the obstruction. We
      performed a study to determine the feasibility of imaging retained
      intracanalicular plugs with ultrasound biomicroscopy (UBM). METHODS: We performed
      in vitro evaluation of an EagleVision punctal plug and a Herrick intracanalicular
      plug to obtain information about the UBM characteristics of the two plugs. We
      then performed UBM in two patients with suspected intracanalicular plugs, one
      with prolapse of an EagleVision punctal plug into the canaliculus and one with
      bilateral epiphora secondary to inserted intracanalicular Herrick plugs. RESULTS:
      In both cases, UBM enabled location of the plugs within the canalicular system at
      the level of obstruction. INTERPRETATION: UBM is a useful diagnostic tool in
      determining the presence and location of a presumed retained intracanalicular
      plug, either placed directly within the canaliculus or prolapsed into the
      canaliculus from a punctal position.

PMID- 15491040
TI  - Giant annular posttraumatic choroidal rupture.

PMID- 15491041
TI  - Congenital fibrosis of the extraocular muscles with brain-stem abnormalities: a
      novel finding.

PMID- 15491042
TI  - Bilateral symmetric semiannular outer retinopathy.

PMID- 15491043
TI  - Corneal bee sting: full-thickness penetration in a patient wearing a contact
      lens.

PMID- 15491044
TI  - Alveolar soft-part sarcoma of the orbit: report of three cases.

PMID- 15491045
TI  - Orbital extramedullary plasmacytoma leading to exenteration.

PMID- 15491046
TI  - Capillary hemangioma of the caruncle.

PMID- 15491047
TI  - Stable amorphous danazol nanostructured powders with rapid dissolution rates
      produced by spray freezing into liquid.
AB  - The objective of this study was to produce, by spray freezing into liquid (SFL)
      technology, high-potency, high glass transition temperature (Tg) danazol/polymer
      powders that remain amorphous and exhibit high dissolution rates after 6 months.
      Three polymers were investigated, including polyvinylpyrrolidone (PVP) K-15,
      poloxamer 407, and PEG 8000. The physicochemical properties of SFL powders were
      characterized by X-ray diffraction (XRD), scanning electron microscopy, particle
      size distribution, surface area analysis, moisture content, and dissolution rate.
      The influence of moisture content, drug potency, and excipient type on Tg of SFL
      powders was investigated using modulated differential scanning calorimetry
      (mDSC). XRD results indicated that danazol was amorphous for each added
      excipient. The surface area of danazol/PVP K-15 powders (89.8 m2/g) was higher
      than that of danazol/PEG 8000 (12.0 m2/g) and danazol/poloxamer 407 (5.49 m2/g).
      The SFL powders with the various excipient types exhibited similar and
      significantly enhanced dissolution rates relative to micronized bulk danazol. As
      the potency of danazol in the SFL danazol/PVP K-15 powders was increased from 33%
      to 91%, the Tg decreased from 126 degrees C to 104 degrees C. The SFL powders,
      which were packaged in sealed 30-mL glass vials with a desiccant, were physically
      stable when stored at 25 degrees C for 6 months, based on dissolution rates and
      mDSC and XRD measurements. SFL danazol/PVP K-15 powders with high surface areas
      and high glass transition temperatures remain amorphous and exhibit rapid
      dissolution rates after 6 months' storage.

PMID- 15491048
TI  - Influence of the size of micronized active pharmaceutical ingredient on the
      aerodynamic particle size and stability of a metered dose inhaler.
AB  - Pharmaceutical inhalers are often used to treat pulmonary diseases. Only active
      pharmaceutical ingredient (API) particles from these inhalers that are less than
      approximately 5 microm are likely to reach the lung and be efficacious. This
      study was designed to investigate the impact of micronized API particle size on
      the aerodynamic particle size distribution (PSD) profile and the particle size
      stability of a suspension metered dose inhaler (MDI) containing propellant HFA
      227 (1,1,1,2,3,3,3 heptafluoropropane) and a corticosteroid. The median API
      particle size ranged from 1.1 microm to 1.8 microm (97% to 70% of particles <3
      microm, respectively). This study showed that increasing the particle size of the
      API used to manufacture a suspension MDI product increased the aerodynamic PSD of
      the MDI product. Furthermore, upon storage of the MDI product under temperature
      cycling conditions, samples containing larger-size API particles were less stable
      with respect to their aerodynamic PSD than those with smaller-size API particles.
      It was found that size-dependent particle growth and/or aggregation of the
      suspended API may be occurring as a result of temperature cycling. In conclusion,
      this study has shown that the particle size of the raw API impacts the properties
      and stability of the emitted aerosol spray. Based on the findings from this
      study, it is recommended that the API particle size be carefully controlled in
      order to meet specifications set for the finished MDI product.

PMID- 15491049
TI  - The acidic complexation of tetracycline with sucralfate for its mucoadhesive
      preparation.
AB  - The complex of antibiotics with sucralfate (SF) was prepared with acid. The
      mechanism of the complexation and some factors concerning the preparation, which
      influence the mucoadhering property, were studied. The complexation was confirmed
      by the change in color and instrumental analysis. The acidic complex appeared to
      be produced by reagglomeration of SF preliminary particles. It was suggested that
      the amide or amine groups of tetracycline (TC) and aluminum moieties of SF serve
      as the binding sites. The potential of multiple binding sites and a priority in
      them were suggested by the Scatchard plot analysis. The additional amounts of
      acid and the increase in the surface area increased the number of sites. The
      amount of the additional acid appeared to be the most important factor during the
      preparation of the acidic complex. The appropriate amount of acid added appeared
      to produce a complex rich in TC. However, an excess amount might cause the excess
      dissociation of aluminum moieties, which destroys the mucoadhesive paste-forming
      property.

PMID- 15491050
TI  - Determining the critical micelle concentration of a novel lipid-lowering agent,
      disodium ascorbyl phytostanyl phosphate (FM-VP4), using a fluorescence
      depolarization procedure.
AB  - The objective of this study was to determine the critical micelle concentration
      (CMC) of a novel water-soluble plant sterol derivative (FM-VP4) using a
      fluorescence depolarization method. The CMC was determined by 1,6-diphenyl-1,3,5
      hexatriene (DPH) fluorescence depolarization. Test solutions of various
      concentrations of sodium dodecylsulphate (SDS) as a positive control or FM-VP4 in
      water were spiked with 2 microL of 4 mM DPH in tetrahydrofuran (THF) and left
      overnight to equilibrate in a dark chamber. Fluorescence of each solution was
      measured at room temperature using a Perseptive Biosystems Cytofluor Series 4000
      multi-well plate reader. Fluorescence intensity increases as DPH is incorporated
      into the hydrophobic core of micelles. Thus, the CMC is the value at which an
      abrupt increase in intensity is observed. These points were observed at 8 mM and
      0.014 mM for SDS and FM-VP4, respectively. Sodium dodecylsulphate was used as a
      positive control and supports the validity of our results, as the literature
      values of SDS are reported to be between 8-8.3 mM. The CMC of FM-VP4 is reported
      to be 0.014 mM.

PMID- 15491051
TI  - Heat-induced formulation inhomogeneity of a three-component suspension.
AB  - A suspension formulation containing sarafloxacin HCl, triamcinolone acetonide,
      and clotrimazole was developed for the treatment of otitis externa in dogs. The
      potency for the three active ingredients in this suspension was monitored at 25
      degrees C and 40 degrees C for up to 3 months. The potencies of triamcinolone and
      clotrimazole were found unchanged, but the potency of sarafloxacin HCl in the
      samples stored at 40 degrees C for 1 month varied significantly between samples.
      However, assay inconsistency for sarafloxacin HCl was not seen in samples stored
      at 25 degrees C. Under an optical microscope, large crystals were found in the 40
      degrees C stability samples but not in the 25 degrees C samples. The large
      crystals in 40 degrees C samples were identified as sarafloxacin by high
      performance liquid chromatography (HPLC). This finding suggests that crystal
      growth of sarafloxacin took place at 40 degrees C during storage, leading to the
      formation of larger crystals and the consequent sampling nonuniformity and assay
      inconsistency. The solid-state properties of these crystals were further
      evaluated using hot-stage microscopy and Fourier transform infrared (FTIR)
      analysis. The results indicate that the crystal growth of sarafloxacin was most
      likely attributed to a change in the hydration form of sarafloxacin.

PMID- 15491052
TI  - Development and characterization of liposomal disodium ascorbyl phytostanyl
      phosphates (FM-VP4).
AB  - The specific objectives of this project were (1) to develop liposomal disodium
      ascorbyl phytostanyl phosphate (FM-VP4) formulations, (2) to develop a liquid
      chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) assay for
      quantification of FM-VP4 in liposomal formulations and plasma sample, and (3) to
      characterize liposomal FM-VP4 formulations by finding optimal drug-to-lipid
      ratios and determining the degradation of FM-VP4 in liposomes. Section 2
      describes an LC/MS/MS assay developed for the identification and quantification
      of FM-VP4 in liposomal formulations to provide estimates of drug concentrations
      and encapsulation efficiency. The extra step of removing plasma proteins prior to
      LC/MS/MS assay yields an analysis of FM-VP4 in plasma samples. Section 3
      describes experiments designed to find the optimal drug-to-lipid ratio for
      liposomal FM-VP4 formulations by comparing encapsulation efficiencies and varying
      the lipid compositions. Additionally, this section details our degradation
      studies to determine if liposomes have any protective effects on FM-VP4; these
      studies tested various lipid compositions at 37 degrees C in rabbit plasma. The
      mechanism of how FM-VP4 lowers low-density lipoprotein (LDL) cholesterol and
      total cholesterol levels in various animal models is presently unknown. However,
      before the mechanism of action could be studied, FM-VP4 first had to be delivered
      efficiently into plasma or cultured cell. The low systemic bioavailability and
      cellular uptake of FM-VP4 further suggested the importance of finding an
      efficient delivery vehicle for this drug. This project proposed a framework for
      such delivery and paves the way for further investigation into how FM-VP4 works
      in vivo and in vitro.

PMID- 15491053
TI  - Tableting of Eudragit RS and propranolol hydrochloride solid dispersion: effect
      of particle size, compaction force, and plasticizer addition on drug release.
AB  - The application of a solid dispersion (SD) system of propranolol HCl and Eudragit
      RS was evaluated in the preparation of prolonged release tablets. The effects of
      SD size fraction, compaction force, and inclusion of plasticizers [namely
      diethylphtalate (DEP) and triethylcitrate (TEC)] on crushing strengths of
      matrices and release profile of drug were also investigated. The results showed
      that when compressed as a tablet, the SD system was more efficient in prolonging
      drug release than physical mixture. This effect was due to formation of much
      harder tablets of the SD system (crushing strength 8.5 kg) compared with those of
      physical mixtures (crushing strength 2.7 kg). All matrices of the SD system
      showed release rate patterns that were best described by the Higuchi equation. It
      was also shown that the rate of drug release decreased from 19.8% to 9.13% min(
      1/2) as the SD size fraction decreased from 300-350 to 125-250 microm. However,
      further reduction of size fraction did not significantly affect tablet crushing
      strength and drug release rate. Increase in compaction force from 5 to 30 kN
      increased the crushing strength of matrices from 2.9 to 13.6 kg. However, the
      rate of drug release remained nearly unchanged beyond compaction pressure of 10
      kN, indicating that crushing strength of matrices in the range of 8.5-13.6 kg did
      not affect drug release rate. The addition of 5% or 10% of either plasticizer
      (DEP or TEC) led to an increase in crushing strength of matrices and more
      retardation of drug release. This effect was more pronounced for higher
      concentrations of plasticizers. This effect was probably due to more plastic
      deformation of matrices under the compaction force, which helped matrices to
      retain their shape throughout the dissolution test.

PMID- 15491054
TI  - Potential mechanisms by which Peceol increases the gastrointestinal absorption of
      amphotericin B.
AB  - PURPOSE: The purpose of this study was to ascertain how the incorporation of AmpB
      into a glyceride-rich excipient Peceol significantly increased Amphotericin B's
      (AmpB) gastrointestinal absorption in white male Sprague-Dawley rats. Based on
      preliminary studies, our working hypothesis was that incorporation of AmpB into
      mixed micelles composed of Peceol would significantly enhance gastro-intestinal
      (GI) tract absorption by increasing lymphatic drug transport and decreasing P
      glycoprotein (PGP)-mediated drug efflux. METHODS: I. Lymphatic Transport STUDIES:
      Following an overnight fast (12-16 hr) and 48 hr postsurgery, rats were divided
      into two treatment groups and received a single-dose oral gavage (1 mL total
      volume) at 0700 h of either desoxycholate (DOC)-AmpB (5 mg AmpB/kg; n = 6 at each
      time point) or AmpB incorporated into 100% Peceol (Peceol-AmpB; 5 mg AmpB/kg; n =
      6 at each time point). Mesenteric lymph samples were obtained prior to and at 0-4
      hr, 4-6-hr, and 6-8-hr intervals post oral gavage. An equal volume of normal
      saline (1 mL) was administered intravenously to the animal following each blood
      draw to prevent fluid depletion throughout the duration of the study. Lymph was
      immediately harvested by centrifugation and analyzed for drug by high-performance
      liquid chromatography (HPLC). II. Multidrug Resistance 1 (mdr-1) STUDIES: Caco-2
      cells were seeded at 10,000 cells/cm2 in T-75 flasks. When the cells reached 80%
      confluency, they were treated for 1 day and 7 days with 0.1% to 1.0% (v/v) Peceol
      or media alone (control). Following treatment, total RNA was isolated using
      TRIzol reagent, followed by reverse transcription into single-stranded cDNA.
      Polymerase chain reactions (PCR) were performed with specific primers for mdr-1.
      The PGP protein was determined by Western Blot Analysis. RESULTS: Mean weight of
      rats was not significantly different prior to and following drug administration.
      Similarly, kidney, liver, lung, spleen, and heart weights were not different
      between DOC-AmpB and Peceol-AmpB treatment group. A significantly greater amount
      of AmpB was transported through the mesenteric lymph duct for all the time
      intervals used following the administration of Peceol-AmpB treatment group
      compared to the administration of DOC-AmpB (suspension). A significant lower mdr
      1 mRNA and PGP protein expression within Caco-2 cells was observed following 1
      and 7 days treatment with Peceol 0.1% to 1.0% (v/v) compared to nontreated
      controls. CONCLUSIONS: Taken together, these findings suggest that Peceol
      increases the gastrointestinal absorption of AmpB by increasing the amount of
      drug that is transported through the mesenteric lymph duct and by decreasing mdr
      1 mRNA and PGP protein expression, resulting in lower PGP-mediated AmpB efflux.

PMID- 15491055
TI  - Development and manufacture of diacetylmorphine/caffeine sachets for inhalation
      via 'chasing the dragon' by heroin addicts.
AB  - In 1998, two clinical trials were started in The Netherlands to evaluate the
      effect of coprescription of heroin and methadone on the mental and physical
      health and social functioning of chronic, treatment-resistant, heroin-dependent
      patients. Since 75-85% of the heroin addicts in The Netherlands use their heroin
      by "chasing the dragon," one of the two study arms concerned the coprescription
      of inhalable heroin. A pharmaceutical dosage form for inhalable heroin was
      developed for this trial, consisting of a 3:1 powder mixture of diacetylmorphine
      base and caffeine anhydrate. We describe the manufacturing process that was
      developed for filling sachets with this mixture in four dosages using a micro
      dose auger filler. In order to control product quality, in-process controls were
      developed to monitor the filling process and quality control tests were performed
      on the finished product. In-process control results have shown the filling
      process to be accurate and precise. The diacetylmorphine/caffeine sachets were
      shown to comply with the specifications for content and uniformity of mass. The
      finished product was found to be stable for 2 years when stored at 25 degrees C,
      60% relative humidity and for 6 months when stored at 40 degrees C, 75% relative
      humidity.

PMID- 15491056
TI  - Flowability measurements of pharmaceutical powder mixtures with poor flow using
      five different techniques.
AB  - Four different tablet formulations for direct compression with poor flow
      properties were tested regarding flowability using five different techniques:
      Hausner ratio, avalanching behavior, powder rheometer, uniaxial tester, and
      Jenike tester. In addition, the behavior of three of the formulations during
      emptying of the mixer and tableting was observed and compared to the results of
      the flowability measurements. The rank order correlation of the formulations was
      generally the same with all techniques. The flow properties measured by the
      different techniques reflected the behavior during processing of the powder
      mixtures.

PMID- 15491057
TI  - Tota mulier in mamma (the whole woman is her breast).

PMID- 15491058
TI  - Fetal cell/tissue therapy in adult disease: a new horizon in regenerative
      medicine.
AB  - Fetal tissue is the richest source of primordial stem cells and has several
      properties that make it particularly useful for transplantation. It is superior
      to adult (mature) tissue in certain respects. First, fetal cells are capable of
      proliferating faster and more often than mature, fully differentiated cells. This
      means that these donor cells are able to quickly reverse the lost function of the
      host. In addition, these fetal cells can often differentiate in response to the
      environmental cues around them. This is because of their location--they can grow,
      elongate, migrate, and establish functional connections with other cells around
      them in the host. It has been found that fetal tissue is not easily rejected by
      the recipient due to the low levels of histocompatibility antigens in the fetal
      tissue. At the same time, angiogenic and trophic factors are at high levels,
      enhancing their ability to grow once they are transplanted. Since early fetal
      hematopoietic tissue lacks lymphocytes, graft vs host reactions are minimized.
      Fetal cells tend to survive excision, dissection, and grafting better because
      they generally do not have long extensions or strong intercellular connections.
      Finally, fetal tissue can survive at lower oxygen levels than mature cells. This
      would make them more resistant to the ischemic conditions found during
      transplantation or in vitro situations. Studies on fetal cell/tissue transplant
      have been encouraging. Fetal tissue can be used in different indications, for
      instance, fetal liver transplants may be used in combating aplastic anemia,
      placental umbilical cord whole blood transfusion can serve as an emergency
      alternative to adult whole blood transfusion, fetal adrenal transplant has been
      tried in combating intractable pain in arthritis, and fetal thymic transplant in
      combating leucopenia in non-Hodgkin's lymhoma and other immunodeficiency
      conditions like DiGeorge Syndrome, only to name a few. Fetal brain tissue
      transplant has also been done in a heterotopic site and the proliferation of the
      tissue has been observed. Neurotransplantation with fetal tissue in Parkinsonism
      shows positive results in some globally accepted studies. There are futuristic
      potential uses of fetal tissue in bioengineering through coating/seedling of
      fetal tissue on implants, stents and other artificial surgical life-saving
      devices to improve their functioning, and it may also extend the life of these
      costly gadgets. By properly using pre-HLA fetal tissue seedling in orthopedic,
      thoracic and also neurosurgical appliances, there could be a reduction of long
      term irritation sequelae of the implant and the host interphase, and thus, a
      better device, i.e., a more biofriendly interphase could be developed. This may
      help in the reduction of pseudomembrane formation, loss of patency and other
      resultant TH2 reactions of the host system.

PMID- 15491059
TI  - Infections of the lower female genital tract during childhood and adolescence.
AB  - PURPOSE: To review the pathogenesis, clinical presentation, diagnosis and
      treatment of lower female genital tract infections at a young age. METHODS:
      Review study. CONCLUSIONS: Lower female genital tract infections at a young age
      may involve the vulva, the vagina and, less frequently, the fallopian tubes. Good
      knowledge of the physiology and anatomy of the respective areas plays an
      important role in the diagnosis and treatment of vulvovaginitis. Candida albicans
      is the most frequent cause of infection, while Gardnerella vaginalis, Chlamydia
      trachomatis, Mycoplasma, and Trichomonas vaginalis are rarer ones. The clinical
      presentation includes a variety of symptoms and signs, with vaginal discharge
      being the prominent one. Treatment should be causative after careful
      investigation while preventive advice is mandatory.

PMID- 15491060
TI  - A comparison in concentration of heat shock proteins (HSP) 70 and 90 on chorionic
      villi of human placenta in normal pregnancies and in missed miscarriages.
AB  - PURPOSE: To investigate the role of heat shock protein (HSP) on the chorionic
      villi of human placental cells and to compare the concentration of placental
      HSP70 & 90 in term deliveries and in missed miscarriages. MATERIALS AND METHODS:
      Fifty products of conception from women who experienced first trimester missed
      miscarriage and 50 placentas from women who gave birth at term were studied. An
      immunohistochemical investigation was carried out with which we marked the
      localization of heat shock proteins 70 and 90 on the syncytiotrophoblastic,
      cytotrophoblastic, stromal and blood vessel cells, using specific antibodies
      which can detect the presence of those proteins on light microscopy. We compared
      their expression with the normal placental tissue of term pregnancies and with
      material acquired from first trimester missed miscarriages. An indirect
      immunoperoxidase method was applied using polyclonal antibodies against HSP70 and
      HSP90 on formalin-fixed paraffin-embedded tissues. RESULTS: Expression of HSP90B
      was increased in chorionic villi of first trimester missed miscarriages
      concerning syncytiotrophoblasts, cytotrophoblasts, vessel and stroma cells
      compared to full-term placentas. There was a statistically significant increase
      of HSP90A expression in chorionic villi of first trimester missed miscarriages,
      concerning only the cytotrophoblast cells, compared to full-term placentas.
      Expression of HSP70 cognate protein was significantly increased in chorionic
      villi of first trimester missed miscarriages, concerning syncytiotrophoblastic
      cells only, compared to full-term placentas. Finally, HSP70 inducible protein was
      significantly increased in chorionic villi of first trimester missed miscarriages
      concerning syncytiotrophoblasts, cytotrophoblasts, vessel and stroma cells
      compared to full-term placentas. CONCLUSIONS: The results of the present study
      have sufficiently shown that there is an increase of HSP70 & 90 expression in
      chorionic villi of first trimester missed miscarriages compared to full-term
      placentas and this increase may have an important implication on the miscarriage
      process.

PMID- 15491062
TI  - Urodynamic alterations after pelvic floor exercises for treatment of stress
      urinary incontinence in women.
AB  - The following study improves the effectiveness of pelvic floor exercise in women
      with stress urinary incontinence. A group of 27 women with stress urinary
      incontinence performed specific pelvic floor exercises twice a week for 45
      minutes under a therapist's supervision for a period of 12 weeks. This group had
      urodynamic and urethral pressure profile studies and filled in a daily diary. The
      patients self-evaluated their symptoms. After the therapy, the urodynamic and
      urethreal pressure profile studies were repeated and the results were: 66.7%
      patients were self-evaluated as cured; 14.8% improved and 18.5% unchanged. The
      urodynamic results showed that 48.2 % of the patients did not have urinary loss,
      however, 51,8% of the patients that had a loss showed an increase in vesicle
      volume, and only 7.3% remained unchanged. The results show that pelvic floor
      exercises are an effective and low cost treatment for stress urinary incontinence
      rehabilitation.

PMID- 15491061
TI  - Fine needle aspiration cytology of the ovary: is it reliable?
AB  - PURPOSE OF INVESTIGATION: The purpose of this study was to evaluate the cytologic
      findings from the fluid of ovarian cysts in comparison with the histologic
      diagnosis. METHODS: Over a four-year period all women with single ovarian cysts
      and no evidence of malignancy from ultrasound examination and tumour marker
      levels were included in the study. Prior to removal of the cyst, fluid was
      aspirated from the cyst and prepared for cytologic examination. Subsequently the
      ovarian cyst wall and biopsy from the ovary were sent for histologic examination.
      The cytologic findings were compared to the histologic diagnosis. RESULTS: The
      material of the study was 120 ovarian specimens from 107 women. Twenty-four (20%)
      of the specimens submitted for cytology were non diagnostic and a comparison
      between cytologic and histologic findings was possible in 96 cases. The
      sensitivity and the specificity of fine needle aspiration (FNA) cytology of the
      ovary was 25% and 97%, respectively. CONCLUSIONS: FNA cytology of the ovary is an
      accurate method for predicting benign ovarian histologic findings in carefully
      selected populations.

PMID- 15491063
TI  - Indication of myomectomy during pregnancy from Doppler ultrasonography.
AB  - Myomas during pregnancy must be evaluated carefully, especially in relation to
      possible premature delivery or spontaneous miscarriage. We wanted to find out
      whether the addition of Doppler assessment could help in the management of these
      cases. We found that from all cases of myomas during pregnancy, the most common
      association with impairment of the fetoplacental unit flow was found in the cases
      with submucous myomas and the subgroup of those with intramural myomes which show
      etc. growth during pregnancy. However myomectomy is generally not considered to
      be indicated to prevent pregnancy complications except for women with a history
      of myoma-related complications. In pregnancies with myomas, preserving the
      pregnancy is one goal but different risk factors have to be taken into account at
      the same time.

PMID- 15491064
TI  - Venous thromboembolism in pregnancy. A case report of deep venous thrombosis
      (DVT) in puerperium.
AB  - The authors describe a case of DVT during pregnancy in a 41-year-old woman who
      had a normal haemocoagulative picture during pregnancy and in puerperium (PT,
      PTT, S protein, C protein, ATIII, xdp and fibrinogenous). All the
      haemocoagulative dosages were within the norm and compatible with the gestation
      period. Both homocysteine and antiphospholipid antibodies (mostly in puerperium)
      were always within normal limits. The authors believe that DVT occurs
      infrequently but it is also unforeseeable. Systematic heparin prophylaxis for
      seven to ten days, ante- and postpartum, can prevent this problem.

PMID- 15491065
TI  - Tamoxifen down-regulates CaMKII messenger RNA levels in normal human breast
      tissue.
AB  - Tamoxifen was proven to reduce the incidence of breast cancer by 49% in women at
      increased risk of the disease in the Breast Cancer Prevention Trial. In order to
      identify potential candidates to explain the preventive effect induced by
      tamoxifen on breast cancer, normal breast tissue obtained from 42 fibroadenoma
      patients, randomly assigned to receive placebo or tamoxifen, was analyzed by the
      reverse Northern blot and RT-PCR techniques. The cDNA fragments used on Northern
      blot membranes were generated by the Human Cancer Genome Project funded by the
      Ludwig Institute for Cancer Research and FAPESP (Fundacao de Amparo a Pesquisa do
      Estado de Sao Paulo, Brazil). Total RNA was obtained from normal breast tissue
      from patients with clinical, cytological and ultrasound diagnosis of
      fibroadenoma. After a 50-day treatment with tamoxifen (10 or 20 mg/day) or
      placebo, normal breast tissue adjacent to the tumor was collected during
      lumpectomy with local anesthesia. One differentially expressed gene,
      Calcium/calmodulin-dependent protein kinase II (CaMKII), was found to be down
      regulated during TAM treatment. CaMKII is an ubiquitous serine/threonine protein
      kinase that has been implicated in the diverse effects of hormones utilizing Ca2+
      as a second messenger as well as in c-fos activation. These results indicate that
      the down-regulation of CaMKII induced by TAM might represent alternative or
      additional mechanisms of the action of this drug on cell cycle control and
      response to hormones in normal human breast tissue.

PMID- 15491066
TI  - Plasma albumin level as an indicator of severity of preeclampsia.
AB  - We propose that hypoalbuminemia in preeclampsia is the result of reduced hepatic
      blood flow which is secondary to hypovolemia created by higher filtration
      pressure in the capillaries. Thus, hypoalbuminemia can be identified as an early
      sign in developing preeclampsia. We reviewed the medical records of 60 patients,
      aged 22-28, admitted with a diagnosis of preeclampsia during the third trimester
      of pregnancy. Normotensive patients served as a control group. Albumin levels
      were correlated with severity of the disorder. Levels between 3.0-3.5 g/dl were
      seen in both groups. All patients with severe preeclampsia had values below 3.0
      gm/dl. Serum albumin levels may serve as an indicator of the severity of
      preeclampsia.

PMID- 15491067
TI  - Leptin concentration during different stages of pregnancy.
AB  - OBJECTIVES: To determine the levels of leptin in pregnant females during
      different stages of pregnancy and to correlate these levels to maternal weight,
      body mass index (BMI), neonate weight and neonate BMI. MATERIAL & METHODS: A case
      control study was carried out in which 60 pregnant females were enrolled, but
      only 36 completed the study and 30 non-pregnant females were used as controls.
      Blood samples were collected at the 1st trimester, 2nd trimester and 3rd
      trimester, and after delivery. Serum was used for the estimation of leptin (by
      radioimmunoassay). RESULTS: The results showed that the levels of leptin were
      significantly higher in pregnant females compared to non-pregnant females, but
      significantly decreased after delivery. In pregnant females with gestational
      diabetes the leptin level was insignificantly higher. CONCLUSION: The increase of
      leptin levels may be due to the stimulatory effect of insulin on leptin secretion
      from adipose tissue.

PMID- 15491068
TI  - Retrospective study of a pioneer antenatal screening program with 8,477 pregnant
      women in Brazil.
AB  - PURPOSE OF INVESTIGATION: To analyze the results of a statewide screening program
      inaugurated in 2002 in Mato Grosso do Sul, METHODS: Retrospective audit of the
      screening results of 8,477 pregnant women for 11 diseases in 19 tests. Local
      health centers of the Brazilian Unified System of Health/State Program of
      Pregnant Protection (SUS/PEPG) and central reference processing laboratories,
      both in and out of state were involved. Pregnant women were referred to the
      program by medical staff principally at local health centers, between November
      2002 and February 2003. Primary screening with filter-paper blood samples was
      carried out with positives being resampled and sera appropriately tested.
      RESULTS: The detailed test results are given below; the most frequent diseases
      serodiagnosed were hepatitis B, syphilis, HIV and Chagas' disease. One case of
      maternal phenylketonouria (PKU) was encountered. CONCLUSION: The diagnosis of 11
      diseases of importance for mothers and their offspring provides an
      epidemiological profile of Brazil, but must be matched by opportunities to
      elaborate new control strategies and improve health care during pregnancy.

PMID- 15491069
TI  - Long-term acetaminophen (paracetamol) treatment causes liver and kidney ultra
      structural changes during rat pregnancy.
AB  - Acetaminophen (paracetamol) is an analgesic-antipyretic drug virtually devoid of
      typical anti-inflammatory activity and hence free of some of the side-effects of
      aspirin and related agents (e.g. gastric erosion and bleeding complications). The
      worldwide use of paracetamol as a household analgesic, including during
      pregnancy, prompted us to investigate its potentially deleterious effects in that
      setting. Pregnant rats were treated with paracetamol (150, 500 or 1,500 mg/kg,
      once a day by gavage) from the first day up to term pregnancy. In the group
      treated with the lowest doses, no histological changes were noticed in maternal
      and fetal livers or kidneys when examined under light or electron microscopy.
      With the higher doses, however, various dose-dependent effects of paracetamol
      were observed, namely necrotic areas of the liver seen with light microscope and
      further confirmed by electron microscopy. The kidneys revealed degeneration and
      necrotic foci under light microscopy with ultrastructural derangements.
      Electronmicrographs of the liver revealed hepatocytes bearing translucent bodies
      as a consequence of a dilated smooth endoplasmic reticulum. There were signs of
      necrosis both in the hepatocytes (lysis of mitochondria and presence of lipid
      droplets) and renal tissue (mitochondrial cytolysis in convoluted tubules). Our
      data point out the fact that both maternal and fetal tissues can be adversely
      affected by paracetamol.

PMID- 15491070
TI  - Morphological and morphometric changes in the cervix uteri of the rat at term
      pregnancy induced by hyaluronidase.
AB  - Intracervix injection of hyaluronidase during pregnancy has been proposed to
      accelerate cervix ripening. We evaluated the morphological and morphometric
      changes of the uterine cervix of pregnant rats, caused by the action of this
      enzyme. Ten female rats were equally divided between an experimental group (G II)
      and a control group (G I). On the 20th day of pregnancy, under light microscopy,
      a greater thinning of the superficial muciferous epithelium, with lamina propria
      rich in blood vessels and in eosinophils was found in G II. The histometric count
      of G II showed a smaller number of collagen fibers (average 248 vs 552 in the
      control group) and a greater concentration of eosinophils (average 18.20 vs 9.20
      in the control group). The Student's t-test showed a significant difference in
      collagen fibers (p < 0.0001) and in eosinophils (p < 0.0007). The action of this
      enzyme caused a predominance of flaccid connective tissue, a lower concentration
      of collagen fibers and an increased concentration of eosinophils, confirming its
      utilization in cervix ripening.

PMID- 15491071
TI  - Effect of chronic ritonavir administration on pregnant rats and their fetuses.
AB  - In view of the very important role played by ritonavir in the prevention of
      maternal-fetal HIV-vertical transmission, the aim of this experimental study was
      to evaluate its possible effects on several important obstetric parameters.
      Ritonavir was administered daily to three groups of pregnant rats (E1 = 20 mg/kg;
      E2 = 60 mg/kg; E3 = 180 mg/kg; n = 10 in every group) from 'zero' up to the 20th
      day of pregnancy. Controls (n = 10) were injected with the drug vehicle
      (propyleneglycol) in the same schedule. We evaluated the effects on fetal and
      maternal weight gain, placental weight, number of implantations and resorptions,
      malformations, fertility rate, and maternal and fetal death rates. Body weight
      gain of the E3 group was significantly lower than that of the other groups, most
      likely due to a toxic effect of the highest dose of ritonavir. Ritonavir did not
      affect the number of implantations. Group E3 had five resorptions and some
      reduction in fertility. The mortality rate was significantly affected by
      ritonavir (2/10 maternal deaths in E2 and 4/10 in E3). On the other hand, no
      alterations were observed in the fetuses, a finding which could be due at least
      in part to the protective action of placental P-glycoprotein.

PMID- 15491072
TI  - Resuscitation with modified gelatin causes higher bacterial translocation in
      experimental sublethal hemorrhagic shock.
AB  - The effect of colloidal solutions on bacterial translocation was studied.
      Sublethal hemorrhagic shock was established by blood withdrawal until the mean
      arterial pressure fell to 40 mmHg within 15 min on 36 adult Wistar Albino rats.
      Resuscitation was performed using four different solutions with the same amount
      of blood. Group I (n = 9) 0.9% NaCl, Group II (n = 9) 10% dextran 40, Group III
      (n = 9) 6% hydroxyethyl starch, Group IV (n = 9) 4% modified fluid gelatin.
      Before resuscitation and after anesthesia blood samples were drawn to analyze pH,
      PCO2, PO2, SaO2, HCO3 and ABE values. Twenty-four hours after anesthesia
      laparotomy was performed to obtain tissue samples of the liver, spleen and
      mesenteric lymph nodes. Samples were cultured on EMB and blood agar media.
      Results were analyzed with the one-way ANOVA and Post-hoc test (Tukey's HSD). The
      translocated bacteria were mainly Eschericia coli and three grew in Group I, two
      in Group II, three in Group III and six in Group IV. Although there was a trend
      in difference in bacterial translocation rates among groups, statistical analyses
      revealed no difference among groups (p < 0.05). It can be concluded that
      resuscitation with modified gelatin causes higher bacterial translocation in an
      experimental sublethal hemorrhagic shock model.

PMID- 15491073
TI  - Isolated torsion of the fallopian tube: a case report and review of the
      literature.
AB  - INTRODUCTION: Isolated torsion of the fallopian tube is a very rare condition. It
      occurs without ipsilateral ovarian involvement associated with pregnancy,
      haemosalpinx, hydrosalpinx, ovarian or paraovarian cysts and other adnexal
      alterations or even with an otherwise normal fallopian tube. We document a case
      of isolated torsion of the right fallopian tube associated with hydrosalpinx.
      CASE: The patient was a 39-year-old female, para 2, gravida 4, who was presented
      with acute pelvic pain, nausea and vomiting. Her medical history included an
      appendectomy and right hydrosalpinx diagnosed five months before admission by
      hysterosalpingography because of investigation for secondary infertility. The
      urinary pregnancy test was negative. Pelvic ultrasonography showed a dilated
      folded right tubular structure measuring 7.8 x 2.7 cm with thickened echogenic
      walls and mucosal folds protruding into the lumen; the ovaries and uterus were
      unremarkable. No free fluid in the cul-de-sac was noted. Preoperatively, a
      diagnosis of twisted right fallopian tube was suspected and an exploratory
      laparotomy confirmed the diagnosis of isolated torsion of the oviduct. The
      ipsilateral ovary appeared normal, but the fallopian tube was gangrenous and
      right salpingectomy was performed. The patient became pregnant three months after
      surgery. CONCLUSION: Isolated torsion of the fallopian tube should be considered
      in the differential diagnosis of patients with acute abdomen and previous medical
      history of hydrosalpinx.

PMID- 15491074
TI  - Spontaneous uterine rupture at an unusual site due to placenta percreta in a 21
      week twin pregnancy with previous cesarean section.
AB  - Spontaneous uterine rupture is a rare, but serious complication of placenta
      percreta. This case report is about a spontaneous uterine rupture at an unusual
      site due to placenta percreta in a 21-week twin pregnancy with previous cesarean
      section. A 30-year-old, G3, P2 woman was referred to our unit in the 21st week of
      a twin pregnancy with acute abdomen. An emergency laparotomy was performed with
      the diagnosis of uterine rupture and intra-abdominal hemorrhage. A significant
      hemoperitoneum was found, with both fetuses freely floating in the peritoneal
      cavity. A large transverse rupture at the posterior isthmus wall was detected.
      Subtotal hysterectomy with preservation of both ovaries was performed.
      Pathological investigation of the uterus revealed placenta percreta.

PMID- 15491075
TI  - Medical management of ectopic pregnancy with extremely high beta-HCG levels: a
      case report.
AB  - We report the successful treatment of an unruptured ectopic pregnancy in a
      patient with extremely high beta-human chorionic gonadotropin concentrations. A
      33-year-old woman, gravida 2, para 0, abortus 1, presented to our department due
      to menstrual delay. On transvaginal ultrasonography, she had an unruptured
      ectopic pregnancy (3.5 x 4.5 cm). Her initial beta-HCG concentration was 38,270
      mIU/ml. The administration of methotrexate (50 mg/m2) was performed
      intramuscularly. Serum beta-HCG levels decreased > 15% between post-therapy days
      4 (31,324 mIU/ml) and 7 (13,108 mIU/ml), and did not rise during the subsequent
      weekly controls. In selected cases with unruptured ectopic pregnancy and
      extremely high initial beta-HCG levels, medical management with a single-dose
      methotrexate regimen may be successful.

PMID- 15491076
TI  - [Coexistent diseases in allergic asthmatic patients. A study of 100 cases].
AB  - BACKGROUND: The prevalence of asthma in Mexico is of 12% in the general
      population. Allergic illnesses diminish the quality of life and increase the
      costs of health services. In our country there is a lack of information about
      asthma and the concomitant presence of other allergic diseases in adults.
      OBJECTIVE: To identify the association of asthma with other allergic illnesses in
      adults. MATERIAL AND METHODS: Patients of the Allergy and Clinical Immunology
      Service diagnosed with allergic asthma, according to GINA, were included. The
      studied variables were: age, sex, and the presence of concomitant illnesses,
      doing a descriptive statistic analysis. RESULTS: 100 allergic asthmatic patients
      were included, 69% corresponded to female and 31% to male. The association with
      allergic illnesses was as follows: rhinitis 92%, conjunctivitis 33% and atopic
      dermatitis 5%. In 13% it was associated to sinusitis, which is considered an
      infectious illness. CONCLUSIONS: Asthma has an important association with
      allergic diseases, especially rhinitis. The female group, as well as the age
      group between the third and fourth decades of the life, were the most affected.
      It is important to identify the relationship between asthma and other allergenic
      entities in order to establish a specific treatment, to diminish medical
      attention costs and to improve the quality of life of the patients.

PMID- 15491077
TI  - [Direct cost of care for acute asthmatic crisis at a pediatric emergency
      service].
AB  - BACKGROUND: The acute asthma crisis in emergency services of second level
      hospitals represents one of the highest levels of intake, generating a high
      number of hospitalizations. OBJECTIVE: To determine, in emergency service medical
      attention, the frequency and direct cost related generated by the hospitalization
      of pediatric patients with acute asthma crisis in second level attention of
      Social Security Service (Instituto Mexicano del Seguro Social, IMSS). MATERIALS
      AND METHOD: In 2000, a cohort study was done on pediatric patients with acute
      asthma crisis in a second level hospital. RESULTS: In the cohort of 2,277
      patients, the response to treatment was adequate in 94% (2,141) of the cases, the
      consultation predominated in September (13.6%) and October (12%). The average
      patient was 3 years old and the patients were predominantly male (63.4%). The
      direct cost generated from attending these patients totaled to 342,989.80 USD,
      the monthly cost average was of 28,582.48 USD. DISCUSSION: The use of health
      services is an indirect indicator of morbidity, also referred to as the increase
      of hospitalization and rehospitalization in children between 0 and 4 years old.
      The knowledge of leading factors, the education on long term control, and the
      handling of initial rescue in asthmatic patients are modifiable factors that can
      help reduce the costs generated by the hospitalization of acute cases of this
      disease.

PMID- 15491078
TI  - [Determination of interleukins and IgG4 in patients with allergic rhinitis with
      and without immunotherapy].
AB  - BACKGROUND: Allergic rhinitis is the most common atopic reaction to allergens and
      may persist for many years if not treated. It is never lethal, though it may
      cause morbidity. The IgE synthesis is regulated by inheritance, antigen
      exposition and cytokines; specially Th2 cells, through secretions of the IL4 e
      IL5 that favor IgE production and inflammation rich in eosinophils. OBJECTIVE: To
      determine the difference of IgG4 serum levels, gamma interferon, and interleukins
      of patients with allergic rhinitis, with and without immunotherapy, and healthy
      patients. MATERIAL AND METHODS: In an observational, transversal, prospective,
      comparative and open study 82 (100%) patients were recruited and divided into
      three groups. Group 1 included 15 patients with allergic rhinitis diagnosis and
      positive skin tests without immunotherapy; group 2, 15 patients with allergic
      rhinitis diagnosis and positive skin tests with immunotherapy; group 3, 52
      healthy patients. RESULTS: IL-4, IL-5, IL-6 and IL-12 values were higher in both
      groups of allergic rhinitis, compared with healthy group. There were differences
      in the IL-5 concentrations that were less in patients with allergic rhinitis and
      vaccine than in those without vaccine. The values of IgG4 and gamma interferon
      did not vary and were not found in the studied groups. CONCLUSION: The present
      study proved the existence of significant differences, showed increments in the
      interleukin values among healthy and allergic patients, despite allergic rhinitis
      is a local phenomenon. It is probable that the above is related to the genetic
      tendency to produce a Th2 cytokines pattern which is a characteristic of allergy.
      Allergen immunotherapy modified significantly the IL-5 levels as well as the
      other studied interleukins.

PMID- 15491079
TI  - [Most common allergens in allergic patients admitted into a third-level
      hospital].
AB  - BACKGROUND: Since year 3000 BC, pollenology (science that studies allergens) was
      already known. In the year 49 BC, Herodotus recognized the first case of hay
      fever, Jacob Constant (17th century) described the first case of allergic
      rhinitis and related it to "something" (allergens) that roses emitted. Charles
      Backley (1873) proved the ability of the skin to determine allergic reactions to
      allergens. Today, it is well-known that allergens are able to react with
      environmental exposure, plants and pollens. OBJECTIVE: To know the most common
      allergens in allergic patients who are admitted into a tertiary care hospital.
      MATERIAL AND METHODS: 3,172 electronic expedients of registered allergic patients
      were examined. Only 356 fulfilled the inclusion criteria. Five groups of
      allergens were studied: group 1 (pollens), 2 (fungus), 3 (inhaled allergens), 4
      (food) and 5 (other allergens), the value of seric IgE was registered too.
      RESULTS: The main allergens that were found are: 156 (43.8%) Amaranthus palmeri,
      163 (45.5%) Candida albicans, 262 (73.6%) dust mite, 33 (9.3%) chicken and 4
      (1.2%) apple/pineapple. The main diseases were: 254 (71.3%) allergic rhinitis, 52
      (14.6%) asthma-rhinitis, 39 (11%) asthma and 63 (17.6%) others, the value of
      seric IgE was minimum of 1 and maximum of 9,620 Ul/dL. CONCLUSIONS: Allergens
      affecting patients are not different of what is reported in world-wide
      literature; however, it is of great significance to know this and take it as a
      guideline to achieve clinical improvement with the use of an appropriate
      immunotherapy.

PMID- 15491080
TI  - [Inflammatory mediators in patients with atopic dermatitis after treatment with
      transfer factor].
AB  - BACKGROUND: Atopic dermatitis is a skin inflammatory disease, which is associated
      to high levels of IgE, eosinophiles and change of T lymphocytes. OBJECTIVE: To
      determine if the treatment with transfer factor for moderate atopic dermatitis
      decreases the number of inflammatory cells in the peripheral blood. MATERIAL AND
      METHODS: We selected twenty patients with diagnosis of moderate atopic
      dermatitis. The age range of the patients was between 5 and 45 years old.
      Patients were assigned to one of three groups: group A included patients with
      atopic dermatitis treated with transfer factor: one unit a day for five days, two
      units a week, one unit a week, one unit every fifteen days and one unit a month.
      Group B included ten patients with atopic dermatitis who received conventional
      treatment (hydroxyzine 10 mg/24 h) and the group C was conformed by healthy
      controls. All patients were submitted to basal and final determination of IgE,
      peripheral blood eosinophils, and underpopulation of lymphocytes by flow
      cytometry. Study period was of ten weeks. RESULTS: Levels of IgE were reduced
      respect to the basal value. In the patients of group A there was an increase in
      neutrophils and leukocytes after treatment; however, it was not significant (p =
      0.46). Eosinophils were significantly reduced (p = 0.01). After comparing group A
      to group C the p value was of 0.035. CONCLUSION: In patients with atopic
      dermatitis, after 10 weeks of treatment with transfer factor, the level of IgE
      and peripheral eosinophils was reduced.

PMID- 15491081
TI  - [Renal disease in diabetics. Immunological bases of tubule-interstitial fibrosis
      and glomeruloesclerosis. Current therapeutic approach].
AB  - Susceptibility of kidney to become target of the immunological aggression is
      easily recognizable when we consider the high number of diseases that, with a
      pathogenesis explained by autoimmunity mechanisms, have the kidney as a target
      organ. In diabetes mellitus, hyperglycemic state stimulates different molecular
      factors conditioning tubule-interstitial fibrosis and glomerulosclerosis, among
      them the most important are: formation of products of advanced glycation;
      activation of protein kinase C, activation of the angiotensin II and the
      activation of the nuclear factor kappaB. These factors are closely related to the
      production of inflammatory cytokines and to the progression of renal damage. This
      paper reviews the role of these factors in the renal damage of diabetic patients
      and the effect of some drugs on the progression of the immunological damage.

PMID- 15491082
TI  - Caries vaccine: prospects and proposals.

PMID- 15491083
TI  - A clinical assessment of the effectiveness of mouthwashes in comparison to
      toothbrushing in children.
AB  - The study compared the efficacy of unsupervised tooth-brushing done once a day
      before breakfast (phase 1), with twice daily mouthrinsing with the three
      different commercially available mouthwashes containing 0.2% sodium fluoride
      (phase 2), a combination of 0.03% triclosan and 0.05% sodium fluoride (phase 3),
      and 0.2% chlorhexidine (phase 4) in 20 children aged 13-14 year, in reducing
      dental plaque formation. The results showed that there was a statistically
      significant difference in plaque reduction between phases 1 & 2; 1 & 3; 2 & 4 and
      3 & 4. The mandibular arch harboured more plaque than the maxillary arch in phase
      1 (p<0.05). Irrespective of the mouthwash used, the lingual/palatal surfaces had
      less plaque than the facial surfaces (p<0.05). The mean cumulative plaque scores
      of the mandibular lingual surfaces was more in comparison to the maxillary
      palatal surfaces in phases 1, 2 and 3 (p<0.05). It was therefore, concluded that
      0.2% chlorhexidine was comparable to tooth brushing done once a day, before
      breakfast.

PMID- 15491084
TI  - Inverted central incisor--a case report.
AB  - An unusual case of inverted central incisor in a nine year old girl is reported
      here. The case was diagnosed as an infected dentigerous cyst. The unerupted
      central incisor was placed inverted almost near the ethmoid bone. The cyst was
      enucleated successfully.

PMID- 15491085
TI  - Prevalence of DMFT and fluorosis in the students of Dayer city (Iran).
AB  - The survey was performed using the cross-sectional method on 506 students
      selected using multi-stage random sampling. The fluorosis level according to
      Deans classification and DMFT with its standard method were surveyed. The water
      fluoride level was estimated in 6 town sources twice, using Alizarin chemical
      method. The fluorosis and DMFT prevalence in the samples was determined. A total
      number of 506 students (55.6% boys and 44.4% girls) aged 13 +/- 3 years were
      examined. The water fluoride level was 2.43 +/- 0.23 ppm and in all the samples,
      which was more than normal. 19.9% of the subjects being surveyed were healthy
      43.6% had mild, 25% moderate and 11.5% had severe fluorosis. Severe fluorosis was
      found in 65.8% of girls and 34.2% of boys (p < 0.05). The mean DMFT value was 1.8
      +/- 1.73 and was higher in girls in comparison with boys (p < 0.05).

PMID- 15491086
TI  - Reattachment of fractured fragments of maxillary central incisors--report of a
      case.
AB  - Reattachment of the original tooth fragment to the fractured tooth helps in
      maintaining the tooth's colour, wear resistance, morphology and translucency in
      the restoration. This paper describes the reattachment of fractured fragments
      using metallic post and core in case of a 12 year old patients who suffered a
      complicated facture of maxillary central incisors.

PMID- 15491087
TI  - Comparative evaluation of glass ionomer and resin based fissure sealant using
      noninvasive and invasive techniques--a SEM and microleakage study.
AB  - The efficacy of using invasive and non-invasive techniques was assessed by
      Scanning electron microscopy, and by microleakage of Glass ionomer (GC VII, Fuji)
      and Resin based sealant (Helioseal-F, Ivoclar Vivadent). 100 young premolars were
      used for this study, and they were divided into four groups: Group I: non
      invasive technique GC VII, Group II: Invasive GC VII, Group III: Non-Invasive
      Helioseal-F, Group IV: Invasive, Helioseal-F. 5 teeth from each group were
      evaluated under SEM. It was seen that the flow and adaptation of GC VII was
      slightly better than Helioseal F, and the invasive technique provided the best
      flow and adaptation. For microleakage analysis 5% methylene blue was used. It was
      seen that minimal microleakage was seen in Group IV (P<0.01). Considering the
      recent controversies using resin based sealants, it can be said that GC VII can
      be a viable alternative for pit and fissure sealants.

PMID- 15491088
TI  - Congenital granular cell lesion "congenital epulis"--report of a case.
AB  - Congenital granular cell lesion (CGCL) or "congenital epulis" is a rare lesion of
      newborn also known as Neuman's Tumor, which is benign in nature, mostly occurs as
      a single tumour but rarely as multiple. The histogenesis and natural clinical
      history of the lesion remains obscure. Even with the advent of modem
      histopathological techniques, it has not been possible to depict specific
      cellular features unique to this lesion. This lesion arises from mucosa of
      gingiva either from maxillary or mandibular alveolar ridge. The appearance of the
      lesion is most common in maxillary alveolar ridge than mandibular with
      predominance in females than in the males. The present report describes a case of
      congenital granular cell lesion (CGCL) in the incisor region of mandibular
      alveolar ridge. This lesion was causing feeding problem and was excised under
      local anaesthesia.

PMID- 15491089
TI  - Comparative evaluation of clinical efficacy of gallium and amalgam alloys in
      primary molars.
AB  - The present study was conducted to compare the clinical efficacy (marginal
      integrity and bulk fracture) of two alloys--Galloy (gallium based) and Aristaloy
      (amalgam based) in primary molars. 90 primary molars with initial caries
      formation were selected. 45 were restored with Galloy and 45 with Aristaloy in
      Class I and II preparations. They were evaluated at two-month intervals for 6
      months. The results showed that Galloy performed at par with Aristaloy with
      regards to marginal integrity and bulk fracture. Hence Galloy can be considered
      as an interesting substitute in Pedodontic practice.

PMID- 15491090
TI  - Oral melanotic macule--a case report.
AB  - A melanotic macule is a benign pigmented lesion of oral cavity characterised by
      increase in melanin pigmentation. Presented here is a case report of 12 year old
      girl with black pigmented area on right buccal mucosa. An excision biopsy was
      done which confirmed the diagnosis by as melanotic macule.

PMID- 15491091
TI  - Leach out of inorganic and trace elements at the time of etching.
AB  - The enamel is the hardest biological structure made up of inorganic ions, organic
      substances, trace elements and water and it covers the coronal part of dentin.
      Acid etching causes leaching out of inorganic and trace elements from the enamel
      surface. In the present study leach out pattern of 11 elements from the enamel
      surface during etching was studied.

PMID- 15491092
TI  - Folic acid and phenytoin induced gingival overgrowth--is there a preventive
      effect.
AB  - The role of folic acid (5mg/day) in combination with oral hygiene measures (group
      II) vis-a-vis oral hygiene measures alone (group I) in prevention of phenytoin
      induced gingival overgrowth was investigated in a one-year follow-up study on
      sixty, 8-13-year-old epileptic children receiving phenytoin. The allocation of
      the children to the two groups was done alternately. In these children, at
      baseline, plaque (Silness & Loe), gingivitis (Loe & Silness) and probing depths
      of gingival sulcus were recorded. These parameters were re-evaluated at 3-monthly
      intervals when gingival overgrowth was also recorded (Modified Harris & Ewalt
      Index). It was seen that, after a period of one year, gingival overgrowth
      occurred in 60 and 50 percent children of groups I & II respectively and its
      development, too, was delayed in group II. More cases (93 percent) in group II
      exhibited minimal overgrowth as against 78 percent in group I. The study
      concluded that systemic folic acid prescribed along with phenytoin delays the
      onset and reduces the incidence and severity of gingival overgrowth induced by
      phenytoin.

PMID- 15491093
TI  - [Protective effect of procyanidins from the seedpod of the lotus on myocardial
      ischemia and reperfusion injury in rat].
AB  - AIM: To study the protective effect of procyanidins from the seedpod of the lotus
      (LSPC) on myocardial ischemia and reperfusion in rats. METHODS: Myocardial injury
      model was made by ligating the coronary artery for 30 min followed by reperfusion
      for 45 min in anesthetized rat and 30 min of ischemia followed by 30 min of
      reperfusion in the isolated rat heart. All animals were given the medicine or
      normal saline before the experiment. ET, Ang I, Ang II in the serum, the MDA
      content, SOD activity, NO level, the recovery rate of coronary flow (CF) and
      heart rate (HR) after reperfusion and CK, XO from the myocardial cells were
      observed. RESULTS: LSPC was shown to inhibit the release of ET, Ang II (P < 0.05)
      , and the increase of MDA content (P < 0.05). It was also found to increase the
      SOD activity (P < 0.05) and NO level (P < 0.01). LSPC was found to increase the
      recovery rate of the coronary flow (CF) and heart rate (HR) after reperfusion (P
      < 0.05 or P < 0.01), decrease the release of CK from the myocardial cells (P <
      0.01), depress the XO activity of myocardial tissue (P < 0.05), as well as
      improve the myocyte ultrastructural pathological injury. CONCLUSION: The anti
      ischemia effect of LSPC was related to the mechanism of scavenging the oxygen
      free radicals directly, cutting off the source of free radicals, reducing tissue
      peroxidation, stabilizing the cells membrane, depressing the production of EDCF
      and increasing the NO level as well.

PMID- 15491094
TI  - [Expression of VEGF in endothelial cells and the effects of 2, 3, 5, 4'
      tetrahydroxystilbene-2-O-beta-D-glucoside].
AB  - AIM: To determine the effect of lysophosphatidylcholine (LPC) on the expression
      of vascular endothelial growth factor (VEGF) in human umbilical veins endothelial
      cell line (ECV304) and the inhibitory effect of 2, 3, 5, 4'-tetrahydroxystilbene
      2-O-beta-D-glucoside (ST I) in vitro. METHODS: Exposure to 2.5 mg x L(-1) LPC or
      LPC + ST I for 24 hours, VEGF protein was determined by enzyme-linked
      immunosorbent assay (ELISA). Meanwhile, VEGF mRNA expression in ECV304 was
      examined by in situ hybridization. VEGF165 mRNA was examined by RT-PCR and
      Realtime RT-PCR. RESULTS: LPC upregulated VEGF protein and VEGF mRNA expression
      in the ECV304 cells. ST I was shown to markedly inhibit the LPC-induced increase
      of VEGF protein and VEGF165 mRNA (P < 0.001). CONCLUSION: LPC can induce a strong
      expression of VEGF in ECV304 cells and ST I can inhibit it.

PMID- 15491095
TI  - [Effect of oxyphenamone on sodium and calcium channels of guinea pig myocardial
      cells].
AB  - AIM: To investigate the mechanism of the positive inotropic effect of
      oxyphenamone. METHODS: With the patch clamp technique and whole cell recording,
      the sodium and L type calcium currents of myocytes isolated from ventricular
      myocardium of adult guinea pigs were studied. RESULTS: 5 - 50 micromol x L(-1)
      oxyphenamone not only significantly inhibited Na+ current, but also promoted the
      process of inactivation and prolonged the recovery time of the inactivation. The
      action of oxyphenamone on L type calcium channel was dual. The inward calcium
      current was increased with 2 - 10 micromol x L(-1) oxyphenamone but decreased
      when the concentration of the drug was elevated to 20 - 50 micromol x L(-1).
      CONCLUSION: The mechanism of the positive inotropic effect of oxyphenamone is
      neither due to the activation of sodium channel nor entirely depending upon the
      activation of L type calcium channel. The effects of inhibiting sodium current
      and, at a high concentration, blocking L type calcium current suggest that
      oxyphenamone may have an antiarrhythemia action.

PMID- 15491096
TI  - [Effects of ginkgolide B on lipopolysaccharide-induced TNFalpha production in
      mouse peritoneal macrophages and NF-kappaB activation in rat pleural
      polymorphonuclear leukocytes].
AB  - AIM: To study the effects of ginkgolide B on lipopolysaccharide (LPS)--induced
      TNFalpha production in mouse peritoneal macrophages and NF-kappaB activation in
      rat pleural polymorphonuclear leukocytes. METHODS: L929 crystal violet staining
      assay was used to show the level of TNFalpha released from mouse peritoneal
      macrophages induced by LPS. Electrophoretic mobility shift assay (EMSA) was used
      to determine NF-kappaB binding activities. RESULTS: Ginkgolide B (1, 10 micromol
      x L(-1)) was shown to significantly inhibit LPS (10 mg x L(-1))-induced TNFalpha
      production in mouse peritoneal macrophages, the IC50 was 0.26 micromol x L(-1);
      LPS (1 mg x L(-1)) and PAF (1 nmol , L(-1)) were shown to increase the NF-kappaB
      binding activities in rat pleural polymorphonuclear leukocytes; ginkgolide B (10
      micromol x L(-1)) was found to inhibit LPS (1 mg x L(-1))-induced NF-kappaB
      activation in rat pleural polymorphonuclear leukocytes; ginkgolide B (1, 10
      micromol x L(-1)) was shown to inhibit PAF (1 nmol x L(-1))-induced NF-kappaB
      activation in rat pleural polymorphonuclear leukocytes. CONCLUSION: The
      inhibition of NF-kappaB activation and TNFalpha production might be considered to
      be part of the mechanisms underlying the antiinflammatory action of ginkgolide B;
      PAF is involved in activation of the NF-kappaB pathway stimulated with LPS.

PMID- 15491097
TI  - Protective effects of sodium beta-aescin on ischemia-reperfusion injury in rat
      brain.
AB  - AIM: To investigate the protective effects of sodium beta-aescin on cerebral
      ischemia-reperfusion injury in rats. METHODS: Rats were pretreated with sodium
      beta-aesein for 7 d and then subjected to cerebral ischemia-reperfusion injury
      induced by a middle cerebral artery occlusion (MCAO). The neurological outcome
      was evaluated by the Longa's method; The infarct volume was assessed by
      hemmatoxylin-Eosin staining and the cerebral water content was measured by dry
      weight method. The activities of SOD, GSH-Px, CAT, Na+ -K+ -ATPase and the MDA
      content were measured in the cortex and hippocampus of ischemic and non-ischemic
      hemisphere. RESULTS: Sodium beta-aescin significantly reduced the volume of
      cerebral infarct and water content, and ameliorated the neurological deficit (P <
      0.05). In vehicle-treated rats, the activities of SOD, GSH-Px and Na+ -K+ -ATPase
      in the cortex and hippocampus of ischemic hemisphere were all decreased (P <
      0.01) , while the CAT activity was slightly elevated and the MDA of content was
      significantly increased (P < 0.01) compared with the sham-operated group. After
      treated with sodium beta-aescin, the effects on recovery of SOD, GSH-Px, Na+ -K+ 
      ATPase activities were observed (P < 0.05), and the MDA content was reduced (P <
      0.05). CONCLUSION: These results showed that pretreatment with sodium beta-aescin
      can attenuate brain injury and its antioxidant activity on rats which encountered
      cerebral ischemia-reperfusion.

PMID- 15491098
TI  - [Effect of catechin on bone marrow cell cycle and gene expression of
      hematopoietic growth factors].
AB  - AIM: To study the effect of catechin, the active component of Spatholobus
      suberectus Dunn, on bone marrow cell cycle and the expression of IL-6 and GM-CSF
      mRNA in spleen cells of normal and marrow-depressed mice in order to clarify the
      mechanism of hematopoietic-supportive effect of catechin. METHODS: Flow cytometry
      was adopted to investigate the influence of catechin on bone marrow cell cycle in
      mice and the expression of IL-6 and GM-CSF mRNA induced by catechin in spleen
      cells was detected by RT-PCR technique simultaneously. RESULTS: The cell
      proportion of normal and marrow-depressed mice in G0/G1 phase was reduced
      significantly, while that in S + G2/M phase increased significantly. Being
      induced by catechin, IL-6 mRNA and GM-CSF mRNA in spleen cells were markedly up
      regulated. CONCLUSION: Catechin (2 g x L(-1), intraperitoneally injected to mice
      daily immediately after irradiation for 7 consecutive days) was shown to promote
      the expression of IL-6 mRNA and GM-CSF mRNA in spleen cells of mice, through
      which it can accelerate bone marrow cells of normal mice into cell cycle and help
      those of marrow-depressed mice to get out of "G1-phase-block", enter into cell
      cycle and radically accelerate the proliferation and differentiation of
      hematopoietic stem cell/hematopoietic progenitor cell (HSC/HPC).

PMID- 15491099
TI  - [Studies on the synthesis and antitumor activity of the derivatives of
      cephalotaxine alkaloid esters].
AB  - AIM: To design and synthesize some cephalotaxine and drupacine derivatives with
      different substituentes on C3'-N of taxol side chain. METHODS: Protective side
      chain acid VI (4'S,5'R) was prepared from optically active (2'R,3'S) methyl beta
      phenyl glycidate I in five steps. The desired acids were coupled with
      cephlotaxine and drupacine respectively in the presence of 2-DPC/DMAP, followed
      by acidic hydrolysis and acylating to give novel alkloid esters with different
      substitutes on C3'-N. RESULTS: The seven new esters were studied for antitumor
      activity, the results showed that the antitumor activity was influenced by the
      substituentes on C3'-N. CONCLUSION: It might provide some rational basis for
      further structral modification.

PMID- 15491100
TI  - [Structural modification and bioactivity of cyclovirobuxine D].
AB  - AIM: To search for new compounds for the treatment of cardiovascular diseases by
      structural modification of cyclovirobuxine D. METHODS: According to rational drug
      design principle, a series of cyclovirobuxine D analogues were prepared, and
      their bioactivities were tested. RESULTS: Ten new compounds were syntheized and
      confirmed by spectra. CONCLUSION: Endurance lacking oxygen activity and
      antiarrhythmia effects of some analogues of cyclovirobuxine D were tested. Some
      compounds showed better activity than cyclovirobuxine D.

PMID- 15491101
TI  - [Studies on the chemical constituents of Knoxia corymbosa].
AB  - AIM: To study the chemical constituents of Knoxia corymbosa Willd. METHODS:
      Chromatography was used to isolate and purify the chemical constituents, their
      structures were identified by spectral analysis. RESULTS: Four flavonol
      glycosides were identified as quercetin-7-O-alpha-L-arabinosyl-3-O-beta-D-6"
      acetylglucopyranoside (1), kaempferol-7-O-alpha-L-arabinosyl-3-O-beta-D
      glucopyranoside (2), quercetin-3-O-beta-D-glucopyranoside (3), quercetin-3-O-beta
      D-6"-acetylglucopyranoside (4). CONCLUSION: Compound 1 is a new flavonol
      glycoside. The other flavonol glycosides were isolated from Knoxia corymbosa
      Willd for the first time.

PMID- 15491102
TI  - [Two new flavonoids from the flower of Castanea mollissima Blume].
AB  - AIM: To study the bioactive constituents from the flower of Castanea mollissima
      Blume. METHODS: Compounds were isolated and purified by column chromatography on
      silica gel and polyamide. Structures were determined by various spectroscopic
      data,including UV, IR, 1H and 13CNMR, EIMS and FABMS, 1H-13C-COSY and HMBC.
      RESULTS: Two compounds were isolated from the ethyl acetate fraction of 95%
      ethanol extract and the structures were elucidated as kaempferol-3-O-[6"-(E)-p
      coumaroyl]-alpha-D-mannopyranoside (1) and kaempferol-3-O-[6", 4"-di-(E)-p
      coumaroyl]-alpha-D-mannopyranoside (2). CONCLUSION: Compounds 1 and 2 are new
      compounds, named castanoside A and B respectirely.

PMID- 15491103
TI  - [Biotransformation of dehydroepiandrosterone by hairy root cultures of Anisodus
      tanguticus].
AB  - AIM: To modify the structure of dehydroepiandrosterone (DHEA). METHODS: Using
      hairy root cultures of Anisodus tanguticus to perform biotransformation of DHEA,
      using chromatographic and spectral techniques to isolate and identify the
      products. RESULTS: (1) The MS medium without plant hormone was suitable for the
      growth of the hairy root. (2) DHEA was converted into five products: androst-4
      ene-3, 17-dione (I); 6alpha-hydroxyandrost-4-ene-3, 17-dione (II); 6alpha, 17beta
      dihydroxyandrost-4-ene-3-one (III); androst-4-ene-3, 6, 17-trione (IV) and 17beta
      hydroxyandrost-4-ene-3-one (V). CONCLUSION: It is the first time to use hairy
      root cultures of Anisodus tanguticus for the biotransformation of DHEA and five
      DHEA-related compounds were obtained.

PMID- 15491104
TI  - [Determination of dextrorphan in human plasma and pharmacokinetic study].
AB  - AIM: To develop a sensitive and specific LC/MS/MS method for direct determination
      of dextrorphan in human plasma and to study the pharmacokinetics of dextrorphan.
      METHODS: After a single oral dose of 60 mg dextromethorphan hydrobromide to 18
      healthy Chinese male volunteers, the plasma concentration of dextrorphan, an
      active metabolite of dextromethorphan, was determined. Dextrorphan and internal
      standard chlorpheniramine were extracted from plasma using liquid-liquid
      extraction, then separated on a Zorbax Extend C18 column. The mobile phase
      consisted of methanol-water-formic acid (70:30:1), at a flow-rate of 0.5 mL x
      min(-1). A Finnigan TSQ tandem mass spectrometer equipped with electrospray
      ionization source was used as detector and was operated in the positive ion mode.
      Selected reaction monitoring (SRM) using the precursor to product ion
      combinations of m/z 258 to 157 and m/z 275 to 230 was performed to quantify
      dextrorphan. The pharmacokinetic parameters of dextrorphan were calculated by non
      compartment model statistics. RESULTS: The linear calibration curves were
      obtained in the concentration range of 0.2 - 80 microg x L(-1) Each plasma sample
      was chromatographed within 3.0 min. The intra- and inter-day relative standard
      deviation (RSD) across three validation runs over the entire concentration range
      was less than 8%. Accuracy determined at three concentrations (0.5, 6.0 and 70
      microg x L(-1) for dextrorphan) ranged from 98.8% to 100.6%. Pharmacokinetic
      parameters of dextrorphan was obtained as follows: Tmax was (2.1 +/- 0.7) h, Cmax
      was (14 +/- 8) microg x L(-1), T1/2 was (3.8 +/- 1.8) h, AUC0-t was (60 +/- 37)
      microg x h x L(-1). CONCLUSION: Plasma concentration of the active metablite
      dextrorphan was directly determined. The method is sensitive and convenient, and
      is proved to be suitable for clinical investigation of dextrorphan
      pharmacokinetics and bioequivalence evaluation of formulations containing
      dextromethorphan.

PMID- 15491105
TI  - [Superoxide dismutase biosensor for screening substances possessing scavenging
      superoxide anion activity].
AB  - AIM: To establish a method for screening active substance with scavenging effects
      on superoxide anion in vitro by designed superoxide dismutase biosensor. METHODS:
      The enzyme sensor was built by connecting the immobilized CuZnSOD with optical
      oxygen sensor through a special way. Superoxide anions were generated by auto
      oxidation of pyrogallol. The auto-oxidation speed was examined before and after
      adding samples into the system, and the Vit C having the scavenging radical
      activities was served as a positive control. RESULTS: The limit of biosensor
      detection was 7.0 U in activity, and lifetime of the immobilized enzyme in the
      reaction-cell was above 2 weeks. The scavenging effects on superoxide radicals of
      fifteen active substance were studied in vitro by the sensor, and some of them
      presented scavenging activities. CONCLUSION: The signal from biosensor is stable,
      easy to be determined, and the kinetic information on scavenging superoxide
      radicals could be obtained directly. The biosensor system can be used for
      screening drugs simply and rapidly.

PMID- 15491106
TI  - [Determination of tramadol and its active metabolite O-desmethyltramadol in
      plasma and amniotic fluid using LC/MS/MS].
AB  - AIM: To determinate tramadol and O-desmethyltramadol in human plasma and amniotic
      fluid by LC/MS/MS, and distribution of tramadol and O-desmethyltramadol in
      maternity and fetus were studied. METHODS: Samples containing tramadol, O
      desmethyltramadol and diphenhydramine (internal standard, IS ) were extracted
      using liquid-liquid extraction, followed by liquid chromatographic separation and
      on-line MS/MS using atmospheric pressure chemical ionization as an interface
      detection. The analytes were detected in the selected reaction monitoring mode.
      RESULTS: The calibration curves for tramadol and O-desmethytramadol in plasma and
      amniotic fluid were linear in the range from 8.0 to 800.0 microg x L(-1) (plasma)
      and 1.0 to 400.0 microg x L(-1) (amniotic fluid). The method was applied to the
      measurement of tramadol and O-desmethytramadol concentrations in maternal vein,
      umbilical vein, umbilical artery and amniotic fluid. Following intramuscular pre
      operative administration 1.5 mg x kg(-1) doses of tramadol to parturients, plasma
      concentrations of tramadol were significantly higher than those in amniotic
      fluid. The concentrations of O-desmethyltramadol in plasma were lower, and were
      not detected in amniotic fluid. CONCLUSION: The method is shown to be accurate,
      robust and convenient, and suitable for clinical pharmacokinetics studies of
      tramadol and O-desmethyltramadol.

PMID- 15491107
TI  - [Relative bioavailability of cyclosporine A-loaded hydroxypropyl methylcellulose
      phthalate nanoparticles for oral administration in rats].
AB  - AIM: To study the preparation of hydroxypropyl methylcellulose phthalate (HPMCP)
      nanoparticles and compare its pharmacokinetic characteristics with Neoral.
      METHODS: HPMCP nanoparticles loaded cyclosporine A were prepared by solvent
      nonsolvent method. CyA-HP50 nanoparticles, CyA-HP55 nanoparticles and Neoral were
      orally administered at the dosage of 15 mg x kg(-1) to rats. The CyA
      concentration in blood were determined by HPLC. Pharmacokinetic parameters were
      calculated by 3P97 program. RESULTS: The concentration-time data of the three
      preparations were best fit by two compartment model. The relative bioavailability
      of CyA-HP50 and CyA-HP55 nanoparticles calculated by the AUC0-72 were 82.3% and
      119.6%, bioequivalent to the reference of Neoral. The relative bioavailability of
      CyA-HP55 nanoparticles was 145.3% of CyA-HP50 nanoparticles. CONCLUSION: CyA
      HPMCP nanoparticles could be prepared easily and reproducibly. It was found that
      the oral absorption of CyA can be increased by using the HPMCP nanoparticles.

PMID- 15491108
TI  - [Preparation and characterization of stearic acid-grafted chitosan
      oligosaccharide polymeric micelles].
AB  - AIM: To prepare the micelles of stearic acid-grafted chitosan oligosaccharide and
      investigate the drug release from micelles. METHODS: Mediated by a 1-ethyl-3-(3
      dimethylaminopropyl) carbodiimide (EDC), stearic acid (SA) was covalently
      attached to chitosan oligosaccharide (CSO), and the graft polymer (CSO-SA) was
      obtained. The critical aggregation concentration (CAC) of the CSO-SA was
      determined by measuring the fluorescence intensity of pyrene as a fluorescent
      probe. The effect of various pH dispersed media and concentration of
      tripolyphosphate sodium (TPP) on the micellar size distribution and zeta
      potential measured by light scattering and electrophoretic mobility, was
      investigated. In buffers of different pH, the release profiles of methotrexate
      (MTX) from micelles were evaluated. RESULTS: The CAC value of CSO-SA in deionized
      water was 0.05 g x L(-1). The mean diameter of CSO-SA micelles was 26.7 nm and
      the zeta potential was (55.9 +/- 0.1) mV. With the increase of TPP concentration,
      the size and MTX encapsulation of CSO-SA micelles increased, while the zeta
      potential decreased. With the decrease of pH value of dispersed media, the size
      and zeta-potential of CSO-SA micelles increased, and the MTX encapsulation in CSO
      SA micelles decreased. While the enhancement of drug release from the micelles
      was observed. CONCLUSION: The graft polymer of CSO-SA provides polymeric
      micelles, which possessed a low CAC value in aqueous media. The drug release in
      vitro from CSO-SA micelles was affected by the pH of delivery media.

PMID- 15491109
TI  - [Studies on combined release behaviors of versatile mini-tablets in capsule
      systems and fittings of their mathematical model].
AB  - AIM: To prepare nifedipine (NP) rapid release mini-tablet, sustained release mini
      tablets, pulsed release mini-tablets and delayed-onset sustained release mini
      tablets and develop multiplied pulsed drug delivery system (DDS), site-specific
      DDS, zero-order DDS and quick/slow DDS by various ways. METHODS: Velocity-time (v
      t) equation of each mini-tablet was deduced by non-linear least square model fit.
      The difference of combinations in v-t profiles between theoretical value and test
      value was compared. RESULTS: According to the v-t equations, the combined release
      behaviors were observed directly from v-t profiles and the test values coincided
      with the theoretical profiles. CONCLUSION: The programmed DDS, which consist of a
      variety of mini-tablets with different dosages and combinations in capsules,
      could be predicted by summing up the v-t equation of each tablet.

PMID- 15491110
TI  - Immunocolloidal gold microscopic study on the mechanism of sodium cholate in
      enhancing insulin colonic absorption.

PMID- 15491111
TI  - [Advances in the study of primary auditory cortex. Demostration of its activation
      by functional magnetic resonance imaging].
AB  - PURPOSE: The purpose of this preliminary study has been to demonstrate and
      investigate the activation patterns of the primary auditory cortex (Heschl's
      gyrus = HG) using functional magnetic resonance imaging (fMRI). MATERIAL AND
      METHODS: A 2500 Hz tone stimulus was delivered monoaurally to the right and left
      ear of 15 normal-hearing right-handed volunteers in 20-second on-off cycles. FMRI
      data were obtained using a 1.5-Tesla scanner and processed with SPM2. RESULTS:
      Activated pixels were identified in the transverse temporal gyrus (Heschl's
      gyrus) of both hemispheres in response to pure tone stimuli using cross
      correlation analysis (P < 0.001). Bilateral hemispheric activation was observed
      in all subjects and there was a trend towards contralateral HG activation to the
      stimulated ear. CONCLUSION: These results demonstrate directly that fMRI is a new
      and useful imaging technique to study the complex auditory cortex and it will
      have potential clinical applications in the next future.

PMID- 15491112
TI  - [Hypoacusis-deafness related to perinatal adverse conditions. According to the
      register available in a specialized unit of Ciudad de Mexico. Analysis according
      to birth weight].
AB  - OBJECTIVE: To analyse perinatal adverse conditions related with birth weight in
      160 children with hearing impairment-deafness (prelingual sensorineural hearing
      loss) according to medical data of a specialized medical unit in Mexico City.
      RESULTS: The average age of children was 4 years old +/- 1.7; 61% were male.
      47.5% of the cases had a birthweight between 1,500 and 2,900 g. 90 cases (56%)
      had an abnormal delivery and 68 (42.5%) were first pregnancy cases. A high number
      of cases had delayed breathing, cyanosis, jaundice or respiratory failure. 104
      cases (65%) had deafness and 56 (35%) presented. hearing loss. Only 11% of the
      children had a birth-weight under 1,500 g. 58% of all cases had a birth weight
      lower than 3,000 g. CONCLUSION: The quality of medical assistance provided during
      the perinatal period has a very important role in origin of hearing impairment-
      deafness in this group of children. It is important to increase our knowledge
      about the perinatal adverse conditions in order to establish preventive programs.

PMID- 15491113
TI  - [Determination of postural behaviour patterns in the Spanish healthy population].
AB  - INTRODUCTION: Postural control in a standing position is externally reflected by
      the displacement of the centre of pressure (COP). It is necessary to determine
      COP movement normal patterns in order to obtain an accurate balance assessment.
      MATERIALS AND METHODOLOGY: A non pathological subject group was studied using
      NED/IBV s. v. e. evaluation equipment. Static trials based on Romberg's test were
      undertaken in addition to the analysis trials of voluntary postural control.
      RESULTS: Normal patterns have been obtained for the COP displacement and for the
      maximum forces produced in the anteroposterior and midlateral axes. CONCLUSIONS:
      COP movement comparative analysis, related to postural behaviour patterns of non
      pathological persons, represents an accurate method to assess postural balance in
      a standing position. This information enables the design of individual and
      customised rehabilitation strategies in order to reduce the risk of falling.

PMID- 15491114
TI  - [Intratympanic gentamicin in patients with Meniere's disease: analysis of our
      protocol].
AB  - OBJECTIVE: The aim of this paper is to analyze the peculiarities of a protocol
      for treatment with intratympanic gentamicin in patients with Meniere's disease.
      MATERIAL AND METHODS: 71 patients with unilateral disabling Meniere's disease
      were followed for a period longer than two years after concluding the treatment.
      AAO-HNS criteria for reporting treatment results was followed. Gentamicin was
      applied weekly until of symptoms or signs of vestibular hypofunction were
      noticed. RESULTS: Control of vertigo was obtained in 83% of the patients while in
      24% a second course was needed beacuse of vertigo recurrence. 66% of the patients
      developed a typical syndrome of unilateral vestibular hypofunction in the ear
      treated. CONCLUSIONS: Ending weekly injections of gentamicin for the treatment of
      patients with Meniere's disease when signs of vestibular hypofunction appear
      warrants a control of vertigo similar to that obtained in other series.

PMID- 15491115
TI  - [Surgical treatment of inferior turbinate hypertrophy with argon plasma: a long
      term follow-up in 157 patients].
AB  - Surgical treatment of the inferior turbinate in patients with chronic
      hypertrophic rhinitis that does not respond to medical treatment is a well
      established procedure. CO2 laser, YAG laser, KTP laser, conventional
      electrocautery, cryotherapy, chemosurgery and turbinectomy or submucosal
      turbinectomy have been performed for the removal of nasal obstruction. Argon
      Plasma Coagulation (APC) is a new, innovative technique in Otorhinolaryngology
      which is based on high-frequency electrocoagulation with an argon-gas source. The
      shorter surgical times, the absence of hemorrhagic complications and, in
      rhinosurgery, not requiring any kind of nasal packing are remarkable. Between
      March and November 2000, a group of 157 patients with symptoms of nasal
      obstruction due to hypertrophic inferior turbinates were treated using APC, at
      the Otorhinolaryngology Surgical Department of the Hospital of Dolo (Venice). The
      follow-up period was 24 months. Rhinomanometry was performed to objectively
      measure the nasal obstruction and to verify the postoperative improvement. The
      Student t-test was used for statistical data. After 24 months, 87% (p < 0.001) of
      patients reported to have a better nasal airflow than before the operation. None
      of the patients needed a nasal packing after APC surgery. We review and discus
      the indication, advantages, complications, controversies and long-term results of
      the treatment with APC in rhinosurgery.

PMID- 15491116
TI  - [Perceptual evaluation of dysphonia: correlation with acoustic parameters and
      reliability].
AB  - The perceptual GRBAS scale for analysis of voice quality is quite important
      clinically in voices that cannot be effectively analyzed with a voicing parameter
      method like vocalizations with strong subharmonics and modulations and in chaotic
      or random voices. In the present study, two experiments were performed: Firstly,
      GRBAS/acoustical correlations were investigated in 107 pathological voices.
      Secondly, the GRBAS interrater and intrarater agreement. The severity of
      dysphonia was assesed better by breath related parameters and low fundamental
      frequencies. The presence of subharmonics in the power spectrum had not a
      significant relationship with the degree of roughness. A (asthenic) and S
      (strain) scales. The results of this study show that GRBAS test-retest
      reliability and intrerrater agreement is high.

PMID- 15491117
TI  - [Surgical treatment of primary hyperparathyroidism. A descriptive analysis].
AB  - In the last decades the primary hyperparthyroidism has become a common disease,
      often diagnosed by biochemical chance. The Elche General Hospital Department of
      Otorhinolaryngology has performed 55 parathyroidectomies between November 1996
      and March 2003. Thirty-six cases (65.4%) were diagnosed as primary
      hyperparathyroidism. This disease usually has few symptoms. Since February 2000,
      Elche Hospital has available a device for quick appraisal of parathormone rate,
      allowing us in a few minutes to determine it and with the patient still in the
      operating theatre. The surgery results were: 25 solitary adenomas, 6 double
      adenomas and 5 hyperplasic. All patients became normocalcemic, and there were no
      major complications in this series.

PMID- 15491118
TI  - [Burkitt's nasopharyngeal lymphoma in pediatric age].
AB  - The Burkitt's lymphoma is a haematological neoplasia typical of early ages. In
      our country, the lymphatic nodes affectation is the most usual. We present a case
      report with a 12 year-old boy who consults for a asymptomatic cervical mass. The
      ultimate diagnosic was a nasopharyngeal Burkitt's lymphoma with neck extension.

PMID- 15491119
TI  - [Cervical foreign body. An unusual case].
AB  - Treatment for penetrating neck injuries remains highly controversial. Surgical
      intervention is mandatory in case of a patent wound or if unable to stabilize the
      patient. Otherwise, a selective approach is not an accepted option, although this
      criterion is becoming more popular due to its low morbidity and the likelihood to
      cure some unidentified injuries. We present a patient with a neck trauma caused
      by a metallic rod in a labour accident without any symptoms. The rod penetrated
      into his jugular vein and reached the heart area where it has remained imbedded
      for 5 years.

PMID- 15491120
TI  - Directly linked porphyrin arrays with tunable excitonic interactions.
AB  - On the basis of the Ag(I)-promoted coupling reaction of Zn(II) 5,15-diaryl
      porphyrin that gave a meso-meso-linked diporphyrin, we developed a variety of
      directly linked porphyrin arrays including linear, windmill, gridlike, cyclic,
      and box architectures. Electronic and excitonic interactions are thus fine tuned
      by placing porphyrin chromophores in well-defined arrangements. Photoexcited
      state dynamics of these porphyrin arrays, as revealed by various ultrafast laser
      based measurements, are pertinent to photosynthetic light-harvesting antenna in
      terms of very efficient excitation energy hopping over many porphyrins and lack
      of a defect that acts as energy sink. The conformational flexibility of a meso
      meso-linked diporphyrin has also been used for the fine tuning of excitonic
      interactions as demonstrated by strapped meso-meso diporphyrins and reversible
      switching of energy transfer in a triporphyrin. Triply linked porphyrin arrays
      have also been explored, which exhibit an exceptionally low HOMO-LUMO gap as a
      result of a fully conjugated pi electronic system over a coplanar platform.

PMID- 15491121
TI  - Phosphoryl transfer enzymes and hypervalent phosphorus chemistry.
AB  - The coordination tendencies of phosphorus to form a hexacoordinated state from a
      pentacoordinated state, which might assist in describing the mechanistic action
      of phosphoryl transfer enzymes, are delineated. The factors discussed include
      substrate and transition or intermediate state anionicity, hydrogen bonding,
      packing effects, that is, van der Waals forces, the ease of formation of
      hexacoordinate phosphorus from lower coordinate states, and the pseudorotation
      problem common to nonrigid pentacoordinate phosphorus. In view of the work
      reported in this Account and recent work on enzyme promiscuity and moonlighting
      activities, it is suggested that donor action should play a role in determining
      active site interactions in phosphoryl transfer enzyme mechanisms.

PMID- 15491122
TI  - Metal-assembled modular proteins: toward functional protein design.
AB  - Metal-assembled parallel helix-bundle proteins have been used to investigate
      electron transfer through alpha-helical structures. Fermi Golden Rule distance
      dependence of electron transfer rates was established in a family of designed
      metalloproteins, and the contribution of intrahelical hydrogen bonding to the
      matrix tunneling element was explored. The first steps toward the design of
      functional proteins using dynamic combinatorial assembly of alpha-helical
      structural elements are described.

PMID- 15491123
TI  - Transformations of molecules and secondary building units to materials: a bottom
      up approach.
AB  - A variety of complex inorganic solids with open-framework and other fascinating
      architectures, involving silicate, phosphate, and other anions, have been
      synthesized under hydrothermal conditions. The past few years have also seen the
      successful synthesis and characterization of several molecular compounds that can
      act as precursors to form open-framework and other materials, some of them
      resembling secondary building units (SBUs). Transformations of rationally
      synthesized molecular compounds to materials constitute an important new
      direction in both structural inorganic chemistry and materials chemistry and
      enable possible pathways for the rational design of materials. In this article,
      we indicate the potential of such a bottom-up approach, by briefly examining the
      transformations of molecular silicates and phosphates. We discuss stable
      organosilanols and silicate secondary building units, phosphorous acids and
      phosphate secondary building units, di- and triesters of phosphoric acids, and
      molecular phosphate clusters and polymers. We also examine the transformations of
      metal dialkyl phosphates and molecular metal phosphates.

PMID- 15491124
TI  - Unraveling the structure and mechanism of acetyl-coenzyme A synthase.
AB  - The bifunctional enzyme carbon monoxide dehydrogenase/acetyl-coenzyme A (CoA)
      synthase (CODH/ACS) is a key enzyme in the Wood-Ljungdahl pathway of carbon
      fixation. Carbon monoxide is combined with a methyl group and ultimately
      converted to acetyl-CoA at a unique Ni-containing bimetallic site in the A
      cluster of this enzyme. Despite years of extensive biochemical and spectroscopic
      studies and the recent report of three separate crystal structures, the mechanism
      by which acetyl-CoA is synthesized is still unknown. Over the past two years
      there have been a number of significant developments regarding ACS. This Account
      critically examines these recent developments and especially focuses on those
      areas that are still a matter of debate.

PMID- 15491125
TI  - Understanding nucleic acids using synthetic chemistry.
AB  - This Account describes work done in these laboratories that has used synthetic,
      physical organic, and biological chemistry to understand the roles played by the
      nucleobases, sugars, and phosphates of DNA in the molecular recognition processes
      central to genetics. The number of nucleobases has been increased from 4 to 12,
      generating an artificially expanded genetic information system. This system is
      used today in the clinic to monitor the levels of HIV and hepatitis C viruses in
      patients, helping to manage patient care. Work with uncharged phosphate
      replacements suggests that a repeating charge is a universal feature of genetic
      molecules operating in water and will be found in extraterrestrial life (if it is
      ever encountered). The use of ribose may reflect prebiotic processes in the
      presence of borate-containing minerals, which stabilize ribose formed from simple
      organic precursors. A new field, synthetic biology, is emerging on the basis of
      these experiments, where chemistry mimics biological processes as complicated as
      Darwinian evolution.

PMID- 15491126
TI  - Exploiting the synergy between coordination chemistry and molecular imprinting in
      the quest for new catalysts.
AB  - The synthesis of transition metal active sites by the molecular imprinting of
      polymerizable metal complexes into highly cross-linked organic polymers is
      described. The emphasis of this Account is on the synergy between the long-term
      goals associated with new catalyst development and the more short-term goal of
      addressing fundamental questions in coordination chemistry, particularly
      emphasizing stereochemistry and structure. An argument is presented that the
      latter is necessary for ultimately achieving the more difficult but more
      important goal of designer catalysts that achieve reaction selectivities and
      reactivities not obtainable with traditional homo- or heterogeneous catalysts.

PMID- 15491127
TI  - The virtue of the multifunctional triazene linkers in the efficient solid-phase
      synthesis of heterocycle libraries.
AB  - With the implementation of combinatorial chemistry into the modern drug discovery
      process, the approach to novel diverse heterocycle libraries is an indispensable
      requirement. Triazenes, which are concealed diazonium salts, can be used to link
      functionalized arenes and amines to generate various heterocyclic structures,
      namely, benzoannelated nitrogen heterocycles, upon cleavage from the resin. Since
      triazene anchors are stable toward various reagents and perform well under a
      range of reaction conditions, these multifunctional linkers are well suited for
      automated solid-phase syntheses and the syntheses of complex organic molecules,
      such as natural products, on solid supports.

PMID- 15491128
TI  - Allylsilanes and vinylsilanes from silylcupration of carbon-carbon multiple
      bonds: scope and synthetic applications.
AB  - Silylcupration of multiple bonds (allenes, acetylenes, dienes, and styrenes) has
      become one of the most efficient procedures for the synthesis of vinyl- and
      allylsilanes. These substrates are useful building blocks in organic synthesis
      since they undergo a great variety of silicon-assisted transformations. The
      methodology reported has been widely used in the synthesis of different natural
      products, as well as in the construction of carbo- and heterocycles. In this
      Account, we wish to illustrate our contribution to this field, as well as to
      highlight the contributions of others.

PMID- 15491130
TI  - LNA (locked nucleic acid): high-affinity targeting of complementary RNA and DNA.
AB  - Locked nucleic acid (LNA) is a nucleic acid analogue containing one or more LNA
      nucleotide monomers with a bicyclic furanose unit locked in an RNA mimicking
      sugar conformation. LNA oligonucleotides display unprecedented hybridization
      affinity toward complementary single-stranded RNA and complementary single- or
      double-stranded DNA. Structural studies have shown that LNA oligonucleotides
      induce A-type (RNA-like) duplex conformations. The wide applicability of LNA
      oligonucleotides for gene silencing and their use for research and diagnostic
      purposes are documented in a number of recent reports, some of which are
      described herein.

PMID- 15491131
TI  - Conserved gating hinge in ligand- and voltage-dependent K+ channels.
AB  - Ion channels open and close their pore in a process called gating. On the basis
      of crystal structures of two voltage-independent K(+) channels, KcsA and MthK, a
      conformational change for gating has been proposed whereby the inner helix bends
      at a glycine hinge point (gating hinge) to open the pore and straightens to close
      it. Here we ask if a similar gating hinge conformational change underlies the
      mechanics of pore opening of two eukaryotic voltage-dependent K(+) channels,
      Shaker and BK channels. In the Shaker channel, substitution of the gating hinge
      glycine with alanine and several other amino acids prevents pore opening, but the
      ability to open is recovered if a secondary glycine is introduced at an adjacent
      position. A proline at the gating hinge favors the open state of the Shaker
      channel as if by preventing inner helix straightening. In BK channels, which have
      two adjacent glycine residues, opening is significantly hindered in a graded
      manner with single and double mutations to alanine. These results suggest that
      K(+) channels, whether ligand- or voltage-dependent, open when the inner helix
      bends at a conserved glycine gating hinge.

PMID- 15491132
TI  - Conformational analysis of chirally deuterated tunicamycin as an active site
      probe of UDP-N-acetylhexosamine:polyprenol-P N-acetylhexosamine-1-P translocases.
AB  - Tunicamycins are potent inhibitors of UDP-N-acetyl-D-hexosamine:polyprenol
      phosphate N-acetylhexosamine-1-phosphate translocases (D-HexNAc-1-P
      translocases), a family of enzymes involved in bacterial cell wall synthesis and
      eukaryotic protein N-glycosylation. Structurally, tunicamycins consist of an 11
      carbon dialdose core sugar called tunicamine that is N-linked at C-1' to uracil
      and O-linked at C-11' to N-acetylglucosamine (GlcNAc). The C-11' O-glycosidic
      linkage is highly unusual because it forms an alpha/beta anomeric-to-anomeric
      linkage to the 1-position of the GlcNAc residue. We have assigned the (1)H and
      (13)C NMR spectra of tunicamycin and have undertaken a conformational analysis
      from rotating angle nuclear Overhauser effect (ROESY) data. In addition, chirally
      deuterated tunicamycins produced by fermentation of Streptomyces chartreusis on
      chemically synthesized, monodeuterated (S-6)-[(2)H(1)]glucose have been used to
      assign the geminal H-6'a, H-6'b methylene bridge of the 11-carbon dialdose sugar,
      tunicamine. The tunicamine residue is shown to assume pseudo-D-ribofuranose and
      (4)C(1) pseudo-D-galactopyranosaminyl ring conformers. Conformation about the C
      6' methylene bridge determines the relative orientation of these rings. The model
      predicts that tunicamycin forms a right-handed cupped structure, with the
      potential for divalent metal ion coordination at 5'-OH, 8'-OH, and the
      pseudogalactopyranosyl 7'-O ring oxygen. The formation of tunicamycin complexes
      with various divalent metal ions was confirmed experimentally by MALDI-TOF mass
      spectrometry. Our data support the hypothesis that tunicamycin is a structural
      analogue of the UDP-D-HexNAc substrate and is reversibly coordinated to the
      divalent metal cofactor in the D-HexNAc-1-P translocase active site.

PMID- 15491133
TI  - Ca2+ binding in the active site of HincII: implications for the catalytic
      mechanism.
AB  - The 2.8 A crystal structure of the type II restriction endonuclease HincII bound
      to Ca(2+) and cognate DNA containing GTCGAC is presented. The DNA is uncleaved,
      and one calcium ion is bound per active site, in a position previously described
      as site I in the related blunt cutting type II restriction endonuclease EcoRV
      [Horton, N. C., Newberry, K. J., and Perona, J. J. (1998) Proc. Natl. Acad. Sci.
      U.S.A. 95 (23), 13489-13494], as well as that found in other related enzymes.
      Unlike the site I metal in EcoRV, but similar to that of PvuII, NgoMIV, BamHI,
      BglII, and BglI, the observed calcium cation is directly ligated to the pro-S(p)
      oxygen of the scissile phosphate. A calcium ion-ligated water molecule is well
      positioned to act as the nucleophile in the phosphodiester bond cleavage
      reaction, and is within hydrogen bonding distance of the conserved active site
      lysine (Lys 129), as well as the pro-R(p) oxygen of the phosphate group 3' of the
      scissile phosphate, suggesting possible roles for these groups in the catalytic
      mechanism. Kinetic data consistent with an important role for the 3'-phosphate
      group in DNA cleavage by HincII are presented. The previously observed sodium ion
      [Horton, N. C., Dorner, L. F., and Perona, J. J. (2002) Nat. Struct. Biol. 9, 42
      47] persists in the active sites of the Ca(2+)-bound structure; however, kinetic
      data show little effect on the single-turnover rate of DNA cleavage in the
      absence of Na(+) ions.

PMID- 15491135
TI  - Polarized ATR-FTIR spectroscopy of the membrane-embedded domains of the
      particulate methane monooxygenase.
AB  - The particulate methane monooxygenase (pMMO) of Methylococcus capsulatus (Bath)
      is an integral membrane protein that catalyzes the conversion of methane to
      methanol. To gain some insight into the structure-reactivity pattern of this
      protein, we have applied attenuated total reflection Fourier transform infrared
      (ATR-FTIR) spectroscopy to investigate the secondary structure of the pMMO. The
      results showed that ca. 60% of the amino acid residues were structured as alpha
      helices. About 80% of the peptide residues were estimated to be protected from
      the amide (1)H/(2)H exchange during a 21 h exposure to (2)H(2)O. In addition, a
      significant portion of the protein was shown to be sequestered within the bilayer
      membrane, protected from trypsin proteolysis. The ATR-FTIR difference spectrum
      between the intact and the proteolyzed pMMO-enriched membranes revealed
      absorption peaks only in the spectral regions characteristic for unordered and
      beta-structures. These observations were corroborated by amino acid sequence
      analysis of the pMMO subunits using the program TransMembrane topology with a
      Hidden Markov Model: 15 putative transmembrane alpha-helices were predicted.
      Finally, an attempt was also made to model the three-dimensional folding of the
      protein subunits from the sequence using the Protein Fold Recognition Server
      based on the 3D Position Specific Scoring Matrix Method. The C-terminal solvent
      exposed sequence (N255-M414) of the pMMO 45 kDa subunit was shown to match the
      beta-sheet structure of the multidomain cupredoxins. We conclude on the basis of
      this ATR-FTIR study that pMMO is an alpha-helical bundle with ca. 15
      transmembrane alpha-helices embedded in the bilayer membrane, together with a
      water-exposed domain comprised mostly of beta-sheet structures similar to the
      cupredoxins.

PMID- 15491134
TI  - Orientation of calcium in the Mn4Ca cluster of the oxygen-evolving complex
      determined using polarized strontium EXAFS of photosystem II membranes.
AB  - The oxygen-evolving complex of photosystem II (PS II) in green plants and algae
      contains a cluster of four Mn atoms in the active site, which catalyzes the
      photoinduced oxidation of water to dioxygen. Along with Mn, calcium and chloride
      ions are necessary cofactors for proper functioning of the complex. The current
      study using polarized Sr EXAFS on oriented Sr-reactivated samples shows that
      Fourier peak II, which fits best to Mn at 3.5 A rather than lighter atoms (C, N,
      O, or Cl), is dichroic, with a larger magnitude at 10 degrees (angle between the
      PS II membrane normal and the X-ray electric field vector) and a smaller
      magnitude at 80 degrees . Analysis of the dichroism of the Sr EXAFS yields a
      lower and upper limit of 0 degrees and 23 degrees for the average angle between
      the Sr-Mn vectors and the membrane normal and an isotropic coordination number
      (number of Mn neighbors to Sr) of 1 or 2 for these layered PS II samples. The
      results confirm the contention that Ca (Sr) is proximal to the Mn cluster and
      lead to refined working models of the heteronuclear Mn(4)Ca cluster of the oxygen
      evolving complex in PS II.

PMID- 15491136
TI  - Interfacial binding of bee venom secreted phospholipase A2 to membranes occurs
      predominantly by a nonelectrostatic mechanism.
AB  - The secreted phospholipase A(2) from bee venom (bvPLA(2)) contains a membrane
      binding surface composed mainly of hydrophobic residues and two basic residues
      that come in close contact with the membrane. Previous studies have shown that
      the mutant in which these two basic residues (K14 and R23) as well as three other
      nearby basic residues were collectively changed to glutamate (charge reversal),
      like wild-type enzyme, binds with high affinity to anionic phospholipid vesicles.
      In the present study, we have measured the equilibrium constants for the
      interaction of wild-type bvPLA(2), the charge-reversal mutant (bvPLA(2)-E5), and
      the mutant in which the five basic residues were changed to neutral glutamine
      (bvPLA(2)-Q5) with phosphatidylcholine (PC) vesicles containing various amounts
      of the anionic phosphatidylserine (PS). Remarkably, bvPLA(2)-E5 with an anionic
      membrane binding surface binds more tightly to vesicles as the mole percent of PS
      is increased. Computational studies predict that this is due to a significant
      upward shift in the pK(a) of E14 (and to some extent E23) when the enzyme binds
      to PC/PS vesicles such that the carboxylate of the glutamate side chain near the
      membrane surface undergoes protonation. The experimental pH dependence of vesicle
      binding supports this prediction. bvPLA(2)-E5 binds more weakly to PS/PC vesicles
      than does wild-type enzyme due to electrostatic protein-vesicle repulsion coupled
      with the similar energetics of desolvation of basic residues and glutamates that
      accompanies enzyme-vesicle contact. Studies with bvPLA(2)-Q5 show that only a
      small fraction of the total bvPLA(2) interfacial binding energy ( approximately
      10%) is due to electrostatics.

PMID- 15491137
TI  - Thermodynamics of mRNA 5' cap binding by eukaryotic translation initiation factor
      eIF4E.
AB  - Translation of mRNA in eukaryotes begins with specific recognition of the 5' cap
      structure by the highly conserved protein, eIF4E. The thermodynamics of eIF4E
      interaction with nine chemical cap analogues has been studied by means of
      emission spectroscopy. High-sensitivity measurements of intrinsic protein
      fluorescence quenching upon cap binding provided equilibrium association
      constants in the temperature range of 279 to 314 K. A van't Hoff analysis yielded
      the negative binding enthalpies for the entire cap analogue series, -16.6 to -81
      kJ mol(-1), and the entropies covering the range of +40.3 to -136 J mol(-1) K(-1)
      at 293 K. The main enthalpic contributions come from interactions of the
      phosphate chains and positively charged amino acids and the cation-pi stacking of
      7-methylguanine with tryptophans. A nontrivial, statistically important
      isothermal enthalpy-entropy compensation has been detected (T(c) = 399 +/- 24 K),
      which points to significant fluctuations of apo-eIF4E and indicates that the cap
      binding microstate lies 9.66 +/- 1.7 kJ mol(-1) below the mean energy of all
      available conformational states. For five cap analogues, large and positive heat
      capacity changes have been found. The values of DeltaC(p) degrees correlate with
      the free energies of eIF4E binding due to stiffening of the protein upon
      interaction with cap analogues. At biological temperatures, binding of the
      natural caps has both favorable enthalpy and favorable entropy. Thermodynamic
      coupling of cap-eIF4E association to intramolecular self-stacking of dinucleotide
      cap analogues strongly influences the enthalpies and entropies of the binding,
      but has a negligible effect on the resultant DeltaG degrees and DeltaC(p) degrees
      values.

PMID- 15491138
TI  - Structural studies on a protein-binding zinc-finger domain of Eos reveal both
      similarities and differences to classical zinc fingers.
AB  - The oligomerization domain that is present at the C terminus of Ikaros-family
      proteins and the protein Trps-1 is important for the proper regulation of
      developmental processes such as hematopoiesis. Remarkably, this domain is
      predicted to contain two classical zinc fingers (ZnFs), domains normally
      associated with the recognition of nucleic acids. The preference for protein
      binding by these predicted ZnFs is not well-understood. We have used a range of
      methods to gain insight into the structure of this domain. Circular dichroism, UV
      vis, and NMR experiments carried out on the C-terminal domain of Eos (EosC)
      revealed that the two putative ZnFs (C1 and C2) are separable, i.e., capable of
      folding independently in the presence of Zn(II). We next determined the structure
      of EosC2 using NMR spectroscopy, revealing that, although the overall fold of
      EosC2 is similar to other classical ZnFs, a number of differences exist. For
      example, the conformation of the C terminus of EosC2 appears to be flexible and
      may result in a major rearrangement of the zinc ligands. Finally, alanine
      scanning mutagenesis was used to identify the residues that are involved in the
      homo- and hetero-oligomerization of Eos, and these results are discussed in the
      context of the structure of EosC. These studies provide the first structural
      insights into how EosC mediates protein-protein interactions and contributes to
      our understanding of why it does not exhibit high-affinity DNA binding.

PMID- 15491139
TI  - Structural analysis of Pseudomonas 1-aminocyclopropane-1-carboxylate deaminase
      complexes: insight into the mechanism of a unique pyridoxal-5'-phosphate
      dependent cyclopropane ring-opening reaction.
AB  - 1-Aminocyclopropane-1-carboxylate (ACC) deaminase is a pyridoxal 5'-phosphate
      (PLP) dependent enzyme catalyzing the opening of the cyclopropane ring of ACC to
      give alpha-ketobutyric acid and ammonia as the products. This ring cleavage
      reaction is unusual because the substrate, ACC, contains no abstractable alpha
      proton and the carboxyl group is retained in the product. How the reaction is
      initiated to generate an alpha-carbanionic intermediate, which is the common
      entry for most PLP-dependent reactions, is not obvious. To gain insight into this
      unusual ring-opening reaction, we have solved the crystal structures of ACC
      deaminase from Pseudomonas sp. ACP in complex with substrate ACC, an inhibitor, 1
      aminocyclopropane-1-phosphonate (ACP), the product alpha-ketobutyrate, and two d
      amino acids. Several notable observations of these structural studies include the
      following: (1) a typically elusive gem-diamine intermediate is trapped in the
      enzyme complex with ACC or ACP; (2) Tyr294 is in close proximity (3.0 A) to the
      pro-S methylene carbon of ACC in the gem-diamine complexes, implicating a direct
      role of this residue in the ring-opening reaction; (3) Tyr294 may also be
      responsible for the abstraction of the alpha-proton from d-amino acids, a prelude
      to the subsequent deamination reaction; (4) the steric hindrance precludes
      accessibility of active site functional groups to the l-amino acid substrates and
      may account for the stereospecificity of this enzyme toward d-amino acids. These
      structural data provide evidence favoring a mechanism in which the ring cleavage
      is induced by a nucleophilic attack at the pro-S beta-methylene carbon of ACC,
      with Tyr294 as the nucleophile. However, these observations are also consistent
      with an alternative mechanistic possibility in which the ring opening is acid
      catalyzed and may be facilitated by charge relay through PLP, where Tyr294
      functions as a general acid. The results of mutagenesis studies corroborated the
      assigned critical role for Tyr294 in the catalysis.

PMID- 15491140
TI  - Molecular cloning of bovine cardiac muscle heat-shock protein 70 kDa and its
      phosphorylation by cAMP-dependent protein kinase in vitro.
AB  - The 70-kDa heat-shock protein (Hsp70) has been cloned and sequenced from bovine
      cardiac muscle. On the basis of sequence features, the gene corresponds to the
      cytoplasmic form of Hsp70. This cardiac Hsp70 cDNA clone has an open reading
      frame of 1926 bp coding for 641 amino acids and a predicted molecular mass of
      70.25 kDa. Comparison of the amino acid sequence revealed an extensive sequence
      identity with other species of Hsp70. Escherichia coli expressed cardiac Hsp70
      stimulated a 2-fold increase in calcineurin (CaN) activity. Notably, we observed
      that Hsp70 directly interacts with CaN using a pull-down assay. Furthermore,
      expressed cardiac-specific Hsp70 was phosphorylated in vitro by cAMP-dependent
      protein kinase. Phosphorylation resulted in the incorporation of 0.1 mol of
      phosphate per mol of Hsp70. The phosphorylated Hsp70 was unable to activate the
      phosphatase activity of CaN. This is the first demonstration that Hsp70 is
      phosphorylated by cAMP-dependent protein kinase and provides an on/off switch for
      the regulation of CaN signaling by Hsp70.

PMID- 15491141
TI  - Lipidic carriers of siRNA: differences in the formulation, cellular uptake, and
      delivery with plasmid DNA.
AB  - RNA interference (RNAi) has become a popular tool for downregulating specific
      gene expression in many species, including mammalian cells [Novina, C. D., and
      Sharp, P. A. (2004) The RNAi revolution, Nature 430, 161-164]. Synthetic double
      stranded RNA sequences (siRNA) of 21-23 nucleotides have been shown in particular
      to have the potential to silence specifically gene function in cultured mammalian
      cells. As a result, there has been a significant surge of interest in the
      application of siRNA in functional genomics programs as a means of deciphering
      specific gene function. However, for siRNA functional genomics studies to be
      valuable and effective, specific silencing of any given target gene is essential,
      devoid of nonspecific knockdown and toxic side effects. For this reason, we
      became interested in investigating cationic liposome/lipid-mediated siRNA
      delivery (siFection) as a meaningful and potentially potent way to facilitate
      effective functional genomics studies. Accordingly, a number of cationic
      liposome/lipid-based systems were selected, and their formulation with siRNA was
      studied, with particular emphasis on formulation parameters most beneficial for
      siRNA use in functional genomics studies. Cationic liposome/lipid-based systems
      were selected from a number of commercially available products, including
      lipofectAMINE2000 and a range of CDAN/DOPE systems formulated from different
      molar ratios of the cationic cholesterol-based polyamine lipid N(1)
      cholesteryloxycarbonyl-3,7-diazanonane-1,9-diamine (CDAN) and the neutral helper
      lipid dioleoyl-L-alpha-phosphatidylethanolamine (DOPE). Parameters that were been
      investigated included the lipid:nucleic acid ratio of mixing, the extent of
      cationic liposome/lipid-nucleic acid complex (lipoplex) formation plus medium
      used, the lipoplex particle size, the mode of delivery, and dose-response
      effects. Results suggest that concentrations during siRNA lipoplex (LsiR)
      formation are crucial for maximum knockdown, but the efficacy of gene silencing
      is not influenced by the size of LsiR particles. Most significantly, results show
      that most commercially available cationic liposome/lipid-based systems
      investigated here mediate a significant nonspecific downregulation of the total
      cellular protein content at optimal doses for maximal specific gene silencing and
      knockdown. Furthermore, one pivotal aspect of using siRNA for functional genomics
      studies is the need for at least minimal cellular toxicity. Results demonstrate
      that CDAN and DOPE with and without siRNA confer low toxicity to mammalian cells,
      whereas lipofectAMINE2000 is clearly toxic both as a reagent and after
      formulation into LsiR particles. Interestingly, LsiR particles formulated from
      CDAN and DOPE (45:55, m/m; siFECTamine) seem to exhibit a slower cellular uptake
      than LsiR particles formulated from lipofectAMINE2000. Intracellularly, LsiR
      particles formulated from CDAN and DOPE systems also appear to behave
      differently, amassing in distinct but diffuse small nonlysosomal compartments for
      at least 5 h after siFection. By contrast, LsiR particles formulated from
      lipofectAMINE2000 accumulate in fewer larger intracellular vesicles.

PMID- 15491142
TI  - Thermodynamics of denaturant-induced unfolding of a protein that exhibits
      variable two-state denaturation.
AB  - Free energy changes (DeltaG(degrees)(N-->D)) obtained by denaturant-induced
      unfolding using the linear extrapolation method (LEM) are presumed to reflect the
      stability differences between native (N) and denatured (D) species in the absence
      of denaturant. It has been shown that with urea and guanidine hydrochloride
      (GdnHCl) some proteins exhibit denaturant-independent (DeltaG(degrees)(N-->D)).
      But with several other proteins urea and GdnHCl give different (DeltaG(degrees)(N
      ->D)) values for the same protein, meaning that the free energy difference
      between N and D is not the only contribution to one or both (DeltaG(degrees)(N-
      >D)) values. Using beta1, a mutant form of the protein G B1 domain, we show that
      both urea- and GdnHCl-induced denaturations are two-state and reversible but that
      the denaturants give different values for (DeltaG(degrees)(N-->D)). While
      spectral observables are sensitive to the shift between N and D states (between
      states effect), they are not sensitive to denaturant-induced changes that occur
      within the individual N and D states (within state effect). By contrast,
      nonspectral observables such as Stokes radius and thermodynamic observables such
      as proton uptake/release are often sensitive to both "between states" and "within
      state" effects. These observables, along with spectral measurements, provide
      descriptions of urea- and GdnHCl-induced denaturation of beta1. Our results
      suggest that in the predenaturation concentration range GdnHCl changes the free
      energy of the native ensemble in a nonlinear manner but that urea does not. As
      with RNase A and beta-lactoglobulin, beta1 exhibits variable two-state behavior
      with GdnHCl-induced denaturation in that the free energy of the native ensemble
      in the predenaturation zone changes (varies) with GdnHCl concentration in a
      nonlinear manner.

PMID- 15491144
TI  - Role of inhibitor aliphatic chain in the thermodynamics of inhibitor binding to
      Escherichia coli enoyl-ACP reductase and the Phe203Leu mutant: a proposed
      mechanism for drug resistance.
AB  - The antibacterial target enoyl-acyl carrier protein (ACP) reductase is a
      homotetrameric enzyme that catalyzes the last reductive step of fatty acid
      biosynthesis. In the present paper, four 2-(2-hydroxyphenoxy)phenol inhibitors,
      wherein the 4-position substituent varied from H to n-propyl, were studied to
      determine the contribution of the aliphatic chain to the binding to the wild-type
      (wt) enoyl-ACP reductase from Escherichia coli (FabI) and a drug-resistant
      mutant, (F203L)FabI, in which phenylalanine 203 is mutated to leucine.
      Thermodynamic parameters of ternary complex formation (enzyme-NAD(+)-inhibitor)
      were determined by isothermal titration calorimetry. The inhibitor affinity to wt
      FabI and (F203L)FabI increases with increasing aliphatic chain length, although
      the corresponding affinity for (F203L)FabI is lower, and also, it shows no
      detectable binding to the 4-H inhibitor. A distinguishing feature of inhibitor
      binding to either binary enzyme-NAD(+) complex is the apparent negative
      cooperativity for binding to the tetramer with half-site occupancy. For both
      enzymes, binding is enthalpy, DeltaH, driven. However, binding DeltaH becomes
      less favorable with increasing aliphatic chain length. Increases in affinity are
      found to be exclusively due to favorable changes in solvation entropy.
      Incremental changes in thermodynamic parameters within the series of inhibitors
      binding to wt FabI and (F203L)FabI are approximately the same. However, absolute
      differences between the two enzymes for binding to a given inhibitor are
      significant, suggesting different binding modes. This finding, coupled with a
      binding site conformation that is likely to be more rigid in the mutant, appears
      to result in the drug resistance of (F203L)FabI.

PMID- 15491143
TI  - Crystal structure of Escherichia coli ArnA (PmrI) decarboxylase domain. A key
      enzyme for lipid A modification with 4-amino-4-deoxy-L-arabinose and polymyxin
      resistance.
AB  - Gram-negative bacteria including Escherichia coli, Salmonella typhimurium, and
      Pseudomonas aeruginosa can modify the structure of lipid A in their outer
      membrane with 4-amino-4-deoxy-l-arabinose (Ara4N). Such modification results in
      resistance to cationic antimicrobial peptides of the innate immune system and
      antibiotics such as polymyxin. ArnA is a key enzyme in the lipid A modification
      pathway, and its deletion abolishes both the Ara4N-lipid A modification and
      polymyxin resistance. ArnA is a bifunctional enzyme. It can catalyze (i) the
      NAD(+)-dependent decarboxylation of UDP-glucuronic acid to UDP-4-keto-arabinose
      and (ii) the N-10-formyltetrahydrofolate-dependent formylation of UDP-4-amino-4
      deoxy-l-arabinose. We show that the NAD(+)-dependent decarboxylating activity is
      contained in the 360 amino acid C-terminal domain of ArnA. This domain is
      separable from the N-terminal fragment, and its activity is identical to that of
      the full-length enzyme. The crystal structure of the ArnA decarboxylase domain
      from E. coli is presented here. The structure confirms that the enzyme belongs to
      the short-chain dehydrogenase/reductase (SDR) family. On the basis of sequence
      and structure comparisons of the ArnA decarboxylase domain with other members of
      the short-chain dehydrogenase/reductase (SDR) family, we propose a binding model
      for NAD(+) and UDP-glucuronic acid and the involvement of residues T(432),
      Y(463), K(467), R(619), and S(433) in the mechanism of NAD(+)-dependent oxidation
      of the 4''-OH of the UDP-glucuronic acid and decarboxylation of the UDP-4-keto
      glucuronic acid intermediate.

PMID- 15491145
TI  - Acid-base catalysis in the extradiol catechol dioxygenase reaction mechanism:
      site-directed mutagenesis of His-115 and His-179 in Escherichia coli 2,3
      dihydroxyphenylpropionate 1,2-dioxygenase (MhpB).
AB  - The extradiol catechol dioxygenases catalyze the non-heme iron(II)-dependent
      oxidative cleavage of catechols to 2-hydroxymuconaldehyde products. Previous
      studies of a biomimetic model reaction for extradiol cleavage have highlighted
      the importance of acid-base catalysis for this reaction. Two conserved histidine
      residues were identified in the active site of the class III extradiol
      dioxygenases, positioned within 4-5 A of the iron(II) cofactor. His-115 and His
      179 in Escherichia coli 2,3-dihydroxyphenylpropionate 1,2-dioxygenase (MhpB) were
      replaced by glutamine, alanine, and tyrosine. Each mutant enzyme was
      catalytically inactive for extradiol cleavage, indicating the essential nature of
      these acid-base residues. Replacement of neighboring residues Asp-114 and Pro-181
      gave D114N, P181A, and P181H mutant enzymes with reduced catalytic activity and
      altered pH/rate profiles, indicating the role of His-179 as a base and His-115 as
      an acid. Mutant H179Q was catalytically active for the lactone hydrolysis half
      reaction, whereas mutant H115Q was inactive, implying a role for His-115 in
      lactone hydrolysis. A catalytic mechanism involving His-179 and His-115 as acid
      base catalytic residues is proposed.

PMID- 15491146
TI  - Probing the configurations of formamidopyrimidine lesions Fapy.dA and Fapy.dG in
      DNA using endonuclease IV.
AB  - The formamidopyrimidines Fapy.dA and Fapy.dG are produced in DNA as a result of
      oxidative stress. These lesions readily epimerize in water, an unusual property
      for nucleosides. The equilibrium mixture slightly favors the beta-anomer, but the
      configurational status in DNA is unknown. The ability of endonuclease IV (Endo
      IV) to efficiently incise alpha-deoxyadenosine was used as a tool to determine
      the configuration of Fapy.dA and Fapy.dG in DNA. Endo IV incision of the C
      nucleoside analogues of Fapy.dA was used to establish selectivity for the alpha
      anomer. Incision of alpha-C-Fapy.dA follows Michaelis-Menten kinetics (K(m) =
      144.0 +/- 7.5 nM, k(cat) = 0.58 +/- 0.21 min(-1)), but the beta-isomer is a poor
      substrate. Fapy.dA incision is considerably slower than that of alpha-C-Fapy.dA,
      and does not proceed to completion. Endo IV incision of Fapy.dA proceeds further
      upon rehybridization, suggesting that the lesion reequilibrates and that the
      enzyme preferentially cleaves duplex DNA containing alpha-Fapy.dA. The extent of
      Fapy.dA incision suggests that the lesion exists predominantly ( approximately
      90%) as the beta-anomer in DNA. Endo IV incises Fapy.dG to less than 5% under
      comparable reaction conditions, suggesting that the lesion exists almost
      exclusively as its beta-anomer in DNA.

PMID- 15491147
TI  - Global and local dynamics of the U1A polyadenylation inhibition element (PIE) RNA
      and PIE RNA-U1A complexes.
AB  - The structure and dynamics of the polyadenylation inhibition element (PIE) RNA,
      free and bound to the U1A protein, have been examined using time-resolved FRET
      and 2-aminopurine (2AP) fluorescence. This regulatory RNA, located at the 3' end
      of the U1A pre-mRNA, adopts a U-shaped structure, with binding sites for a single
      U1A protein at each bend (box 1 and box 2). The distance between the termini of
      the arms of the RNA is sensitive to its three-dimensional structure. Using
      Cy3/Cy5 FRET efficiency to monitor binding of Mg(2+), we show that the PIE RNA
      binds two Mg(2+) ions, which results in a restriction of its distance
      distribution of conformations. Local RNA structure probing using 2AP fluorescence
      shows that the structure of box 2 changes in response to Mg(2+) binding, thus
      tentatively locating the ion binding sites. Steady-state FRET data show that the
      distance R between the termini of the PIE RNA stems decreases from 66 A in the
      free RNA, to 58 A when N-terminal RNA binding domains (RBD1) of U1A are bound,
      and to 53 A when U1A proteins bind. However, anisotropy measurements indicate
      that both Cy3 and Cy5 stack on the ends of the RNA. To examine the consequences
      of the restricted motion of the fluorophores, FRET data are analyzed using two
      different models of motion and then compared to analogous data from the
      Cy3/fluorescein FRET pair. We conclude that the error introduced into distance
      calculations by stacking of the dyes is within the error of our measurements.
      Distance distributions of the RNA structures show that the intramolecular
      distance between the arms of the PIE RNA varies on the time scale of the
      fluorescence measurements; the mean distance is dependent on protein binding, but
      the breadth of the distributions indicates that the RNA retains structural
      heterogeneity.

PMID- 15491148
TI  - DNA ligation catalyzed by human topoisomerase II alpha.
AB  - The DNA ligation reaction of topoisomerase II is essential for genomic integrity.
      However, it has been impossible to examine many fundamental aspects of this
      reaction because ligation assays historically required the enzyme to cleave a DNA
      substrate before sealing the nucleic acid break. Recently, a cleavage-independent
      DNA ligation assay was developed for human topoisomerase IIalpha [Bromberg, K.
      D., Hendricks, C., Burgin, A. B., and Osheroff, N. (2002) J. Biol. Chem. 277,
      31201-31206]. This assay overcomes the requirement for DNA cleavage by monitoring
      the ability of the enzyme to ligate a nicked oligonucleotide in which the 5'
      terminal phosphate at the nick has been activated by covalent attachment to the
      tyrosine mimic, p-nitrophenol. The cleavage-independent ligation assay was used
      to more fully characterize the DNA ligation activity of human topoisomerase
      IIalpha. Results suggest that the active site tyrosine contributes little to the
      catalysis of DNA ligation beyond its primary role as an activating/leaving group.
      Although arginine 804 (the residue immediately N-terminal to the active site
      tyrosine) has been proposed to help anchor the 5'-DNA terminus during cleavage,
      conversion of this residue to alanine had only a modest effect on DNA ligation.
      Thus, it appears that arginine 804 does not play an essential role in DNA strand
      joining. In contrast, disruption of base pairing at the 5'-DNA terminus abrogated
      DNA ligation in the absence of a covalent enzyme-DNA bond. Therefore, it is
      proposed that base pairing represents a secondary mechanism for aligning the 5'
      DNA termini for ligation. Finally, the human enzyme appears to ligate the two
      scissile bonds of a cleavage site in a nonconcerted fashion.

PMID- 15491149
TI  - Testis brain ribonucleic acid-binding protein/translin possesses both single
      stranded and double-stranded ribonuclease activities.
AB  - RNA interference (RNAi) is a biological process in which animal and plant cells
      destroy double-stranded RNA (dsRNA) and consequently the mRNA that shares
      sequence homology to the dsRNA. Although it is known that the enzyme Dicer is
      responsible for the digestion of dsRNA into approximately 22 bp fragments, the
      mechanism through which these fragments are associated with the RNA-induced
      silencing complex (RISC) is mostly unknown. To find protein components in RISC
      that interact with the approximately 22 bp fragment, we synthesized a (32)P- and
      photoaffinity moiety-labeled 22 bp dsRNA fragment and used it as bait to fish out
      protein(s) directly interacting with the dsRNA fragment. One of the proteins that
      we discovered by mass spectrometric analysis was TB-RBP/translin. Further
      analysis of this DNA/RNA binding protein showed that it possesses both ssRNase
      and dsRNase activities but not DNase activity. The protein processes long dsRNA
      mainly into approximately 25 bp fragments by binding to the open ends of dsRNA
      and cutting it with almost no turnover due to its high affinity toward the
      products. The activity requires physiological ionic strength. However, with
      single-stranded RNA as substrate, the digestion appeared to be more complete.
      Both ssRNase and dsRNase activities are inhibited by high levels of common RNase
      inhibitors. Interestingly, both activities can be enhanced greatly by EDTA.

PMID- 15491150
TI  - Pyruvate dehydrogenase kinase isoform 2 activity limited and further inhibited by
      slowing down the rate of dissociation of ADP.
AB  - Pyruvate dehydrogenase kinase 2 (PDK2) activity is enhanced by the dihydrolipoyl
      acetyltransferase core (E2 60mer) that binds PDK2 and a large number of its
      pyruvate dehydrogenase (E1) substrate. With E2-activated PDK2, K(+) at
      approximately 90 mM and Cl(-) at approximately 60 mM decreased the K(m) of PDK2
      for ATP and competitive K(i) for ADP by approximately 3-fold and enhanced
      pyruvate inhibition. Comparing PDK2 catalysis +/- E2, E2 increased the K(m) of
      PDK2 for ATP by nearly 8-fold (from 5 to 39 microM), increased k(cat) by
      approximately 4-fold, and decreased the requirement for E1 by at least 400-fold.
      ATP binding, measured by a cold-trapping technique, occurred at two active sites
      with a K(d) of 5 microM, which equals the K(m) and K(d) of PDK2 for ATP measured
      in the absence of E2. During E2-aided catalysis, PDK2 had approximately 3 times
      more ADP than ATP bound at its active site, and the pyruvate analogue,
      dichloroacetate, led to 16-fold more ADP than ATP being bound (no added ADP).
      Pyruvate functioned as an uncompetitive inhibitor versus ATP, and inclusion of
      ADP transformed pyruvate inhibition to noncompetitive. At high pyruvate levels,
      pyruvate was a partial inhibitor but also induced substrate inhibition at high
      ATP levels. Our results indicate that, at physiological salt levels, ADP
      dissociation is a limiting step in E2-activated PDK2 catalysis, that PDK2.[ADP or
      ATP].pyruvate complexes form, and that PDK2.ATP.pyruvate.E1 reacts with
      PDK2.ADP.pyruvate accumulating.

PMID- 15491151
TI  - Pyruvate dehydrogenase kinase isoform 2 activity stimulated by speeding up the
      rate of dissociation of ADP.
AB  - Pyruvate dehydrogenase kinase 2 (PDK2) activity is stimulated by NADH and NADH
      plus acetyl-CoA via the reduction and reductive acetylation of the lipoyl groups
      of the dihydrolipoyl acetyltransferase (E2) component. Elevated K(+) and Cl(-)
      were needed for significant stimulation. Stimulation substantially increased both
      k(cat) and the K(m) for ATP; the fractional stimulation increased with the level
      of ATP. With an E2 structure lacking the pyruvate dehydrogenase (E1) binding
      domain, stimulation of PDK2 was retained, the K(m) for E1 decreased, and the
      equilibrium dissociation constant for ATP increased but remained much lower than
      the K(m) for ATP. Stimulation of PDK2 activity greatly reduced the fraction of
      bound ADP. These results fit an ordered reaction mechanism with ATP binding
      before E1 and stimulation increasing the rate of dissociation of ADP. Conversion
      of all of the lipoyl groups in the E2 60mer to the oxidized form (E2(ox)) greatly
      reduced k(cat) and the K(m) of PDK2 for ATP. Retention over an extended period of
      time of a low portion of reduced lipoyl groups maintains E2 in a state that
      supported much higher PDK2 activity than short-term (5 min) reduction of a large
      portion of lipoyl groups of E2(ox), but reduction of E2(ox) produced a larger
      fold stimulation. Reduction and to a greater extent reductive acetylation
      increased PDK2 binding to E2; conversion to E2(ox) did not significantly hinder
      binding. We suggest that passing even limited reducing equivalents among lipoyl
      groups maintains E2 lipoyl domains in a conformation that aids kinase function.

PMID- 15491153
TI  - Very efficient template/primer-independent DNA synthesis by thermophilic DNA
      polymerase in the presence of a thermophilic restriction endonuclease.
AB  - We have found that, in the presence of a thermophilic restriction endonuclease,
      thermophilic DNA polymerase efficiently synthesizes and amplifies DNA in the
      absence of any added template and primer nucleic acid under isothermal
      conditions. More than 10 microg of DNA can be synthesized by 1 unit of DNA
      polymerase in 1 h, and the reaction proceeds until available dNTPs are consumed.
      We used mostly the Tsp509I restriction endonuclease (recognition sequence:
      decreasing AATT), the TspRI restriction endonuclease (recognition sequence:
      NNCA(G/C)TGNN decreasing), and Vent (exo(-)) and Vent DNA polymerase. The
      synthesized double-stranded DNA has a highly repetitive palindromic sequence,
      e.g. (AAAAATTTTT)(n) and (ATACACTGTATATACAGTGTAT)(n). In every repeating unit,
      there are one or two recognition sites for the restriction enzyme. Our data show
      that the high efficiency of the restriction-endonuclease-DNA-polymerase (RE-pol)
      DNA synthesis results from an efficient exponential amplification involving
      digestion-elongation cycles: a longer DNA with numerous recognition sites for the
      restriction enzyme is digested to short fragments, and the short fragments are
      used as seeds for elongation to synthesize longer DNA. A possible role of RE-pol
      DNA synthesis in the evolutionary development of genetic materials is briefly
      discussed.

PMID- 15491152
TI  - Inhibition of human telomerase activity by an engineered zinc finger protein that
      binds G-quadruplexes.
AB  - The G-quadruplex nucleic acid structural motif is a target for designing
      molecules that could potentially modulate telomere length or have anticancer
      properties. We have recently described an engineered zinc finger protein (Gq1)
      that binds with specificity to the intramolecular G-quadruplex formed by the
      human telomeric sequence 5'-(GGTTAG)(5)-3' (Isalan et al. (2001) Biochemistry 40,
      830-836). Here, we report that Gq1 is able to arrest the action of a DNA
      polymerase on a template-containing telomeric sequence. Inhibition occurs in a
      concentration-dependent manner, probably by forming a stabilized G
      quadruplex.protein complex. Furthermore, Gq1 inhibits the apparent activity of
      the enzyme telomerase in vitro, with an IC(50) value of 74.3 +/- 11.1 nM.
      Possible molecular mechanisms of inhibition are discussed, together with the
      potential for using engineered zinc fingers to interfere with the cellular
      processes associated with telomere function.

PMID- 15491154
TI  - NiFe hydrogenase active site biosynthesis: identification of Hyp protein
      complexes in Ralstonia eutropha.
AB  - Biosynthesis of the NiFe hydrogenase active site is a complex process involving
      the action of the Hyp proteins: HypA-HypF. Here we investigate the mechanism of
      NiFe site biosynthesis in Ralstonia eutropha by examining the interactions
      between HypC, HypD, HypE, and HypF1. Using an affinity purification procedure
      based on the Strep-tag II, we purified HypC and HypE from different genetic
      backgrounds as complexes with other hydrogenase-related proteins and
      characterized them using immunological analysis. Copurification of HypC and HoxH,
      the active site-containing subunit of the soluble hydrogenase in R. eutropha,
      from several different genetic backgrounds suggests that this complex forms early
      in the maturation process. With respect to the Hyp proteins, it is shown that
      HypE and HypF1 formed a stable complex both in vivo and in vitro. Furthermore,
      HypC and HypD functioned as a unit. Together, they were able to interact with
      HypE to form a range of complexes probably varying in stoichiometry. The
      HypC/HypD/HypE complexes did not involve HypF1 but appeared to be more stable
      when HypF1 was also present in the cells. We hypothesize that HypF1 is able to
      modify some component of the HypC/HypD/HypE complex. Since we have also seen that
      HypF1 and HypE form a complex, it is likely that HypF1 modifies HypE. On the
      basis of these results, we propose a complete catalytic cycle for HypE. First, it
      is modified by HypF1, and then it can form a complex with HypC/HypD. This
      activated HypE/HypC/HypD complex could then decompose by donating active site
      components to the immature hydrogenase and regenerate unmodified HypE.

PMID- 15491155
TI  - Properties of the cysteine residues and iron-sulfur cluster of the assimilatory
      5'-adenylyl sulfate reductase from Pseudomonas aeruginosa.
AB  - APS reductase from Pseudomonas aeruginosa has been shown to contain a [4Fe-4S]
      cluster. Thiol determinations and site-directed mutagenesis studies indicate that
      the single [4Fe-4S] cluster contains only three cysteine ligands, instead of the
      more typical arrangement in which clusters are bound to the protein by four
      cysteines. Resonance Raman studies in the Fe-S stretching region are also
      consistent with the presence of a redox-inert [4Fe-4S](2+) cluster with three
      cysteinate ligands and indicate that the fourth ligand is likely to be an oxygen
      containing species. This conclusion is supported by resonance Raman and electron
      paramagnetic resonance (EPR) evidence for near stoichiometric conversion of the
      cluster to a [3Fe-4S](+) form by treatment with a 3-fold excess of ferricyanide.
      Site-directed mutagenesis experiments have identified Cys139, Cys228, and Cys231
      as ligands to the cluster. The remaining two cysteines present in the enzyme,
      Cys140 and Cys256, form a redox-active disulfide/dithiol couple (E(m) = -300 mV
      at pH 7.0) that appears to play a role in the catalytic mechanism of the enzyme.

PMID- 15491156
TI  - NO reductase from Bacillus azotoformans is a bifunctional enzyme accepting
      electrons from menaquinol and a specific endogenous membrane-bound cytochrome
      c551.
AB  - Bacillus azotoformans is a Gram-positive denitrifying soil bacterium, which is
      capable of respiring nitrate, nitrite, nitric oxide, and nitrous oxide under
      anaerobic conditions. It contains a unique menaquinol-dependent nitric oxide
      reductase (qCu(A)NOR) with a Cu(A) center in its small subunit. The qCu(A)NOR
      exhibits menaquinol-dependent NO reductase activity, whereas reduced horse heart
      cytochrome c was inactive. Here we describe the purification of three membrane
      bound c cytochromes from B. azotoformans. Their apparent molecular masses on SDS
      PAGE are approximately 11 kDa. At neutral pH, these c cytochromes are negatively
      charged and the E(m) for all is close to 150 mV. Only one of these c cytochromes,
      which exhibits an alpha-band maximum at 551 nm, acts as a direct electron donor
      to qCu(A)NOR. Further investigation demonstrated that this cytochrome c(551)
      possesses two lipoyl moieties, which presumably function to anchor it to the
      membrane. Steady-state kinetic studies reveal that cytochrome c(551) is a
      noncompetitive inhibitor of NO reduction when menaquinol is used as an electron
      donor. This finding points to the presence of two different electron donation
      pathways in qCu(A)NOR. The ability of qCu(A)NOR to accept electrons from both
      menaquinol and cytochrome c(551) might be related to the regulation of the rate
      of NO reduction especially as a defense mechanism of B. azotoformans against the
      toxicity of NO. Growth experiments in batch culture indeed show that B.
      azotoformans is highly NO tolerant, in contrast to, for example, Paracoccus
      denitrificans that has a monofunctional cytochrome c-dependent NOR. We propose
      that the menaquinol pathway, which has a 4-fold greater maximal activity than the
      pathway via cytochrome c(551), is used for NO detoxification, whereas electron
      donation via the endogenous cytochrome c involves the cytochrome b(6)f complex
      serving the bioenergetic needs of the organism.

PMID- 15491157
TI  - Insight into the polar reactivity of the onium chalcogen analogues of S-adenosyl
      L-methionine.
AB  - S-Adenosyl-L-methionine (AdoMet) is one of Nature's most diverse metabolites,
      used not only in a large number of biological reactions but amenable to several
      different modes of reactivity. The types of transformations in which it is
      involved include decarboxylation, electrophilic addition to any of the three
      carbons bonded to the central sulfur atom, proton removal at carbons adjacent to
      the sulfonium, and reductive cleavage to generate 5'-deoxyadenosyl 5'-radical
      intermediates. At physiological pH and temperature, AdoMet is subject to three
      spontaneous degradation pathways, the first of which is racemization of the
      chiral sulfonium group, which takes place in a pH-independent manner. The two
      remaining pathways are pH-dependent and include (1) intramolecular attack of the
      alpha-carboxylate group onto the gamma-carbon, affording L-homoserine lactone
      (HSL) and 5'-methylthioadenosine (MTA), and (2) deprotonation at C-5', initiating
      a cascade that results in formation of adenine and S-ribosylmethionine. Herein,
      we describe pH-dependent stability studies of AdoMet and its selenium and
      tellurium analogues, Se-adenosyl-L-selenomethionine and Te-adenosyl-L
      telluromethionine (SeAdoMet and TeAdoMet, respectively), at 37 degrees C and
      constant ionic strength, which we use as a probe of their relative intrinsic
      reactivities. We find that with AdoMet intramolecular nucleophilic attack to
      afford HSL and MTA exhibits a pH-rate profile having two titratable groups with
      apparent pK(a) values of 1.2 +/- 0.4 and 8.2 +/- 0.05 and displaying first-order
      rate constants of <0.7 x 10(-6) s(-1) at pH values less than 0.5, approximately 3
      x 10(-6) s(-1) at pH values between 2 and 7, and approximately 15 x 10(-6) s(-1)
      at pH values greater than 9. Degradation via deprotonation at C-5' follows a pH
      rate profile having one titratable group with an apparent pK(a) value of
      approximately 11.5. The selenium analogue decays significantly faster via
      intramolecular nucleophilic attack, also exhibiting a pH-rate profile with two
      titratable groups with pK(a) values of approximately 0.86 and 8.0 +/- 0.1 with
      first-order rate constants of <7 x 10(-6) s(-1) at pH values less than 0.9,
      approximately 32 x 10(-6) s(-1) at pH values between 2 and 7, and approximately
      170 x 10(-6) s(-1) at pH values greater than 9. Degradation via deprotonation at
      C-5' proceeds with one titratable group displaying an apparent pK(a) value of
      approximately 14.1. Unexpectedly, TeAdoMet did not decay at an observable rate
      via either of these two pathways. Last, enzymatically synthesized AdoMet was
      found to racemize at rates that were consistent with earlier studies (Hoffman, J.
      L. (1986) Biochemistry 25, 4444-4449); however, SeAdoMet and TeAdoMet did not
      racemize at detectable rates. In the accompanying paper, we use the information
      obtained in these model studies to probe the mechanism of cyclopropane fatty acid
      synthase via use of the onium chalcogens of AdoMet as methyl donors.

PMID- 15491158
TI  - Isotope and elemental effects indicate a rate-limiting methyl transfer as the
      initial step in the reaction catalyzed by Escherichia coli cyclopropane fatty
      acid synthase.
AB  - Cyclopropane fatty acid (CFA) synthases catalyze the formation of cyclopropane
      rings on unsaturated fatty acids (UFAs) that are natural components of membrane
      phospholipids. The methylene carbon of the cyclopropane ring derives from the
      activated methyl group of S-adenosyl-L-methionine (AdoMet), affording S-adenosyl
      L-homocysteine (AdoHcys) and a proton as the remaining products. This reaction is
      unique among AdoMet-dependent enzymes, because the olefin of the UFA substrate is
      isolated and unactivated toward nucleophilic or electrophilic addition, raising
      the question as to the timing and mechanism of proton loss from the activated
      methyl group of AdoMet. Two distinct reaction schemes have been proposed for this
      transformation; however, neither was based on detailed in vitro mechanistic
      analysis of the enzyme. In the preceding paper [Iwig, D. F. and Booker, S. J.
      (2004) Biochemistry 43, http://dx.doi.org/10.1021/bi048693+], we described the
      synthesis of two analogues of AdoMet, Se-adenosyl-L-selenomethionine (SeAdoMet)
      and Te-adenosyl-L-telluromethionine (TeAdoMet), and their intrinsic reactivity
      toward polar chemistry in which AdoMet is known to be involved. We found that the
      electrophilicity of AdoMet and its onium congeners followed the series SeAdoMet >
      AdoMet > TeAdoMet, while the acidity of the carbons adjacent to the relevant
      heteroatom followed the series AdoMet > SeAdoMet > TeAdoMet. When each of these
      compounds was used as the methylene donor in the CFA synthase reaction, the
      kinetic parameters of the reaction, k(cat) and k(cat) K(M)(-1), followed the
      series SeAdoMet > AdoMet > TeAdoMet, suggesting that the reaction takes place via
      methyl transfer followed by proton loss, rather than by processes that are
      initiated by proton abstraction from AdoMet. Use of S-adenosyl-L-[methyl
      d(3)]methionine as the methylene donor resulted in an inverse isotope effect of
      0.87 +/- 0.083, supporting this conclusion and also indicating that the methyl
      transfer takes place via a tight s(N)2 transition state.

PMID- 15491159
TI  - The tetrameric molecule of conventional kinesin contains identical light chains.
AB  - Conventional kinesin is a multifunctional motor protein that transports numerous
      organelles along microtubules. The specificity of kinesin-cargo binding is
      thought to depend on the type(s) of light chains that a kinesin molecule
      contains. We have shown previously that different isoforms of kinesin light
      chains are associated with different types of cargo, mitochondria and membranes
      of the Golgi complex. Here, we provide evidence that the two light chains present
      within each kinesin molecule are always of the same type. Further, we demonstrate
      that kinesin heavy chains interact with nascent light-chain polypeptides on
      ribosomes. These data suggest that incorporation of the two identical light
      chains into a single kinesin molecule most likely occurs cotranslationally.

PMID- 15491160
TI  - Truncated carboxyl-terminal fragments of beta-amyloid precursor protein are
      processed to amyloid beta-proteins 40 and 42.
AB  - We previously showed that beta-amyloid precursor protein (APP) is cleaved not
      only in the middle of the membrane (gamma-cleavage) but also at novel cleavage
      sites close to the membrane/cytoplasmic boundary (epsilon-cleavage), releasing
      APP intracellular domains (AICDs) 49-99 and 50-99. To learn more about the
      relationship between gamma- and epsilon-cleavage, C-terminally truncated carboxyl
      terminal fragments (CTFs) of APP, especially CTFs1-48 and 1-49 (the postulated
      products that are generated by epsilon-cleavage), were transiently expressed in
      CHO cells. Most importantly, the cells expressing CTF1-49 secreted predominantly
      amyloid beta-protein (Abeta) 40, while those expressing CTF1-48 secreted
      preferentially Abeta42. This supports our assumption that epsilon-cleavage
      precedes Alphabeta production and that preceding epsilon-cleavage determines the
      preference for the final Abeta species. The gamma-secretase inhibitors, L-685,458
      and DAPT, suppressed Abeta production from CTF1-49. Regarding Abeta production
      from CTF1-48, L-685,458 suppressed it, but DAPT failed to do so. A dominant
      negative mutant of presenilin 1 suppressed the production of Abeta40 and 42 from
      both CTFs1-48 and 1-49. These data should shed significant light into the
      mechanism of Abeta production.

PMID- 15491161
TI  - Heme O synthase and heme A synthase from Bacillus subtilis and Rhodobacter
      sphaeroides interact in Escherichia coli.
AB  - Cytochrome c oxidase requires multiple heme and copper cofactors to catalyze the
      reduction of molecular oxygen to water. Although significant progress has been
      made in understanding the transport and incorporation of the copper ions,
      considerably less is known about the trafficking and insertion of the heme
      cofactors. Heme O synthase (HOS) and heme A synthase (HAS) from Rhodobacter
      sphaeroides (Cox10 and Cox15, respectively) and Bacillus subtilis (CtaB and CtaA,
      respectively) have been cloned and expressed in Escherichia coli. Our results
      demonstrate that HOS copurifies with HAS and that HAS copurifies with HOS,
      indicating that HOS and HAS interact and may form a physiologically relevant
      complex in vivo. Consistent with this hypothesis, the presence of HAS alters the
      total level of farnesylated hemes, providing further evidence that HOS and HAS
      interact. Our current working model is that HOS and HAS form a complex and that
      heme O is transferred directly from HOS to HAS. Because of the strong sequence
      similarity and evolutionary relationship between R. sphaeroides and mitochondria,
      our data suggest that this complex may form in eukaryotes as well.

PMID- 15491162
TI  - Site-directed mutagenesis of Thermosynechococcus elongatus photosystem II: the O2
      evolving enzyme lacking the redox-active tyrosine D.
AB  - Site-directed mutagenesis in the photosystem II (PSII) oxygen-evolving enzyme was
      achieved in the thermophilic cyanobacterium Thermosynechococcus elongatus. PSII
      from this species is the focus of attention because its robustness makes it
      suitable for enzymological and biophysical studies. PSII, which lacks the redox
      active tyrosine Tyr(D), was engineered by substituting a phenylalanine for
      tyrosine 160 of the D2 protein. An aim of this work was to engineer a mutant for
      spectroscopy, in particular, for EPR, on the active enzyme. The Tyr(D)(*) EPR
      signal was monitored in whole cells (i) to control the expression level of the
      two genes (psbD(1) and psbD(2)) encoding D2 and (ii) to assess the success of the
      mutagenesis. Both psbD(1) and psbD(2) could be expressed, and recombination
      occurred between them. The D2-Y160F mutation was introduced into psbD(1) after
      psbD(2) was deleted and a His-tag was attached to the CP43 protein. The effects
      of the Y160F mutation were characterized in cells, thylakoids, and isolated PSII.
      The efficiency of enzyme function under the conditions tested was unaffected. The
      distribution and lifetime of the redox states (S(n)() states) of the enzyme cycle
      were modified, with more S(0) in the dark and no rapid decay phase of S(3).
      Although not previously reported, these effects were expected because Tyr(D)(*)
      is able to oxidize S(0) and Tyr(D) is able to reduce S(2) and S(3). Slight
      changes in the difference spectra in the visible and infrared recorded upon the
      formation and reduction of the chlorophyll cation P(680)(+) and kinetic
      measurements of P(680)(+) reduction indicated minor structural perturbations,
      perhaps in the hydrogen-bonding network linking Tyr(D) and P(680), rather than
      electrostatic changes associated with the loss of a charge from Tyr(D)(*)(H(+)).
      We show here that this fully active preparation can provide spectra from the
      Mn(4)CaO(4) complex and associated radical species uncontaminated by Tyr(D)(*).

PMID- 15491163
TI  - A fluorescent alpha-factor analogue exhibits multiple steps on binding to its G
      protein coupled receptor in yeast.
AB  - The yeast alpha-factor receptor encoded by the STE2 gene is a member of the
      extended family of G protein coupled receptors (GPCRs) involved in a wide variety
      of signal transduction pathways. We report here the use of a fluorescent alpha
      factor analogue [K(7)(NBD), Nle(12)] alpha-factor (Lys(7) (7-nitrobenz-2-oxa-1,3
      diazol-4-yl), norleucine(12) alpha-factor) in conjunction with flow cytometry and
      fluorescence microscopy to study binding of ligand to the receptor.
      Internalization of the fluorescent ligand following receptor binding can be
      monitored by fluorescence microscopy. The use of flow cytometry to detect binding
      of the fluorescent ligand to intact yeast cells provides a sensitive and
      reproducible assay that can be conducted at low cell densities and is relatively
      insensitive to fluorescence of unbound and nonspecifically bound ligand. Using
      this assay, we determined that some receptor alleles expressed in cells lacking
      the G protein alpha subunit exhibit a higher equilibrium binding affinity for
      ligand than the same alleles expressed in isogenic cells containing the normal
      complement of G protein subunits. On the basis of time-dependent changes in the
      intensity and shape of the emission spectrum of [K(7)(NBD),Nle(12)] alpha-factor
      during binding, we infer that the ligand associates with receptors via a two-step
      process involving an initial interaction that places the fluorophore in a
      hydrophobic environment, followed by a conversion to a state in which the
      fluorophore moves to a more polar environment.

PMID- 15491164
TI  - Recombinant EWS-FLI1 oncoprotein activates transcription.
AB  - The Ewing's sarcoma family of tumors (ESFT) contains a characteristic
      translocation the chimeric transcript of which is translated to become the EWS
      FLI1 fusion protein. EWS-FLI1 regulates transcription and posttranscriptional
      splicing. Elimination of EWS-FLI1 protein from ESFT cells induces apoptosis and
      reduces xenograft tumor growth. Therefore the production of a biologically active
      recombinant EWS-FLI1 could lead to discoveries that would enhance our mechanistic
      understanding of ESFT. We have cloned, expressed, and purified a biologically
      active recombinant EWS-FLI1 in Escherichia coli using affinity column
      chromatography. A refolding procedure was required to render the recombinant EWS
      FLI1 soluble in relatively native conditions. The structural alterations induced
      by the refolding procedure were monitored by SDS-gel electrophoresis, circular
      dichroism, and steady-state fluorescence spectroscopy. Recombinant EWS-FLI1 under
      native conditions approaches a largely unfolded conformation. Recombinant EWS
      FLI1 protein under native conditions specifically binds to DNA and transcribes
      RNA. Our biologically active recombinant EWS-FLI1 oncoprotein will be useful to
      identify functional molecular partners and inhibitors.

PMID- 15491165
TI  - Cyclic peptides from the loop region of the laminin alpha 4 chain LG4 module show
      enhanced biological activity over linear peptides.
AB  - Laminins, heterotrimeric glycoproteins in the basement membrane, are involved in
      diverse biological activities. So far, five alpha, three beta, and three gamma
      chains have been identified, and at least 15 laminin isoforms exist composed of
      various combinations of the different three chains. The major cell-surface
      receptors for laminins are integrins and proteoglycans, such as dystroglycans and
      syndecans. Previously, we reported that synthetic peptide A4G82 (TLFLAHGRLVFM,
      mouse laminin alpha4 chain residues 1514-1525) showed strong cell attachment and
      syndecan binding activities. On the basis of the crystal structure of the LG
      module and sequence alignment, A4G82 is located in the connecting loop region
      between beta-strands E and F in the laminin alpha4 chain LG4 module. Here, we
      have focused on the structural importance of this E-F loop region for the
      biological activity of the alpha4 chain LG4 module. To determine the importance
      of the loop structure, we synthesized peptide A4G82X (cyclo-A4G82X, Cys
      TLFLAHGRLVFX-Cys, X= norleucine), which was cyclized via disulfide bridges at
      both the N- and C-termini. The cyclic peptides derived from A4G82X inhibited the
      heparin binding activity of the alpha4 chain G domain and promoted HT-1080 cell
      attachment better than the corresponding linear peptides. We determined
      FLAHGRLVFX as a minimal sequence of cyclo-A4G82X important for cell adhesion and
      heparin binding using a series of truncated peptides. Moreover, HT-1080 cell
      attachment to the cyclic peptides was more efficiently blocked by heparin than
      cell attachment to the linear peptides. Furthermore, the cyclic peptides showed
      significantly enhanced syndecan-2-mediated cell attachment activity. These
      results indicate that the activity of A4G82 is highly conformation-dependent,
      suggesting that the E-F loop structure is crucial for its biological activity.

PMID- 15491166
TI  - Traditional GFP-type cyclization and unexpected fragmentation site in a purple
      chromoprotein from Anemonia sulcata, asFP595.
AB  - The purple chromoprotein (asFP595) from Anemonia sulcata belongs to the family of
      green fluorescent protein (GFP). Absorption and emission spectra of asFP595 are
      similar to those of a number of recently cloned GFP-like red proteins of the
      DsRed subfamily. The earlier proposed asFP595 chromophore structure [Martynov, V.
      I.; et al. (2001) J. Biol. Chem. 276, 21012-21016] was postulated to result from
      an "alternative cyclization" giving rise to a pyrazine-type six-membered
      heterocycle. Here we report that the asFP595 chromophore is actually very close
      in chemical structure to that of zFP538, a yellow fluorescent protein
      [Zagranichny, V. E.; et al. (2004) Biochemistry 43, 4764-4772]. NMR spectroscopic
      studies of four chromophore-containing peptides (chromopeptides) isolated under
      mild conditions from enzymatic digests of asFP595 and one chromopeptide obtained
      from DsRed revealed that all of them contain a p-hydroxybenzylideneimidazolinone
      moiety formed by Met-65/Gln-66, Tyr-66/67, and Gly-67/68 of asFP595/DsRed,
      respectively. Two asFP595 chromopeptides are proteolysis products of an isolated
      full-length polypeptide containing a GFP-type chromophore already formed and
      arrested at an earlier stage of maturation. The two other asFP595 chromopeptides
      were isolated as proteolysis products of the purified chromophore-containing C
      terminal fragment. One of these has an oxo group at Met-65 C(alpha) and is a
      hydrolysis product of another one, with the imino group at Met-65 C(alpha). The N
      unsubstituted imino moiety of the latter is generated by spontaneous polypeptide
      chain cleavage at a very unexpected site, the former peptide bond between Cys-64
      C' and Met-65 N(alpha). Our data strongly suggest that both zFP538 and asFP595
      could be attributed to the DsRed subfamily of GFP-like proteins.

PMID- 15491167
TI  - Primary structure elements of spider dragline silks and their contribution to
      protein solubility.
AB  - Spider silk proteins have mainly been investigated with regard to their
      contribution to mechanical properties of the silk thread. However, little is
      known about the molecular mechanisms of silk assembly. As a first step toward
      characterizing this process, we aimed to identify primary structure elements of
      the garden spider's (Araneus diadematus) major dragline silk proteins ADF-3 and
      ADF-4 that determine protein solubility. In addition, we investigated the
      influence of conditions involved in mediating natural thread assembly on protein
      aggregation. Genes encoding spider silk-like proteins were generated using a
      cloning strategy, which is based on a combination of synthetic DNA modules and
      PCR-amplified authentic gene sequences. Comparing secondary structure,
      solubility, and aggregation properties of the synthesized proteins revealed that
      single primary structure elements have diverse influences on protein
      characteristics. Repetitive regions representing the largest part of dragline
      silk proteins determined the solubility of the synthetic proteins, which differed
      greatly between constructs derived from ADF-3 and ADF-4. Factors, such as
      acidification and increases in phosphate concentration, which promote silk
      assembly in vivo generally decreased silk protein solubility in vitro.
      Strikingly, this effect was pronounced in engineered proteins comprising the
      carboxyl-terminal nonrepetitive regions of ADF-3 or ADF-4, indicating that these
      regions might play an important role in initiating assembly of spider silk
      proteins.

PMID- 15491168
TI  - Anionic contribution for fibrous maturation of protofibrillar assemblies of the
      human tau repeat domain in a fluoroalcohol solution.
AB  - Tau protein forms fibrous aggregates in the brain of patients with Alzheimer's
      disease. This type of aggregation in vitro is promoted efficiently by polyanions
      and anionic micelles. Here, we report another cosolvent system that induces the
      fibrous aggregation of human tau four-repeat domain (tau4RD). The protein
      aggregation was primarily achieved by a nonanionic agent 1,1,1,3,3,3-hexafluoro-2
      propanol (HFIP), while the ionic condition was modified by inorganic salts. The
      aggregation analysis by three spectroscopic methods revealed a two-phase kinetics
      of the aggregation of tau4RD in the presence of HFIP at approximately 4-6%. Large
      increases in the light-scattering, the thioflavin-binding, and the secondary
      structure content of tau4RD have progressed within a few minutes at 37 degrees C,
      which was followed by another slower aggregation phase. Electron microscopic
      analysis demonstrated that the amorphous granules are formed in the faster step,
      which acquired a fibrous shape in the slower step in the solution containing
      NaCl. In the absence of the salt, however, the fibrous maturation was inhibited.
      Examination of various salt species in place of NaCl demonstrated that binding of
      anions to the precursor aggregates was essential for the fibrous maturation. On
      the basis of the results, we proposed an aggregation scheme of tau in which the
      formation of a thioflavin-binding intermediate occurred ahead of its fibrous
      maturation. The anionic environment was suggested to play a crucial role in the
      fibrous maturation and, therefore, could be an in vivo determinant of the
      morphology of the aggregates of tau.

PMID- 15491169
TI  - Surface behavior of amphiphilic heteroarm star-block copolymers with asymmetric
      architecture.
AB  - We study the surface behavior of the asymmetric amphiphilic heteroarm
      poly(ethylene oxide) (PEO)/polystyrene (PS) star polymer on solid substrate.
      These star polymers differ in both architecture (four- and three-arm molecules,
      PEO-b-PS(3) and PEO-b-PS(2)) and in the length of PS chains (molecular weight
      from about 10 000 up to 24 000). We observed that, for a given chemical
      composition with a predominant content of hydrophobic blocks, the compression
      behavior of the PS domain structure controls the surface behavior and the final
      morphology of the monolayers. New features of the surface behavior of star-block
      copolymers are high stretching of the PS arms from the interface and enhanced
      stability of the circular PS domain structure, even at high compression. We
      suggest that for asymmetric star-block copolymers both architecture and chemical
      composition heavily favor the formation of highly curved interfaces and, thus,
      more stable circular domain structure with stretched PS arms.

PMID- 15491170
TI  - Topographical parameters for specifying a three-dimensional surface.
AB  - The importance of different surface geometries and thereby the need for versatile
      surface identification by describing a number of different surface features is
      emphasized. A set of topographical parameters for the description of the
      amplitude and spatial and hybrid properties of surfaces was utilized for a
      versatile three-dimensional surface characterization of sol-gel samples with
      different topographies. The image data were measured by atomic force microscopy.
      The results demonstrate the power of the roughness parameters to identify
      surfaces according to their specific characteristics. An example is also given
      about how certain surface topographical properties may control the material
      reactivity.

PMID- 15491171
TI  - A two-state model for the multilamellar structure of a DNA/cationic lipid complex
      in the bulk.
AB  - Polyanionic DNA can bind electrostatically with cationic lipids to form a complex
      used for gene delivery and nanostructure construction. Here, we reveal two
      multilamellar phases, L(I) and L(II), characterized by distinct states of lipid
      packing and DNA conformation in a DNA/cationic lipid complex in the bulk state.
      The L(II) phase, formed when the lipids are in excess of DNA in terms of overall
      ionic charge, is composed of B-DNA confined between the bilayers with the lipid
      tails aligning normal to the lamellar interface. When DNA becomes in excess of
      the lipids, the L(I) phase in which the DNA is bound with the tilted lipid chains
      adopting the A conformation is favored because this configuration offers more
      economical electrostatic binding between these two components.

PMID- 15491172
TI  - Fast initiation of chemical reactions with laser-induced breakdown of a nanoscale
      partition.
AB  - This letter describes a new strategy for initiating a chemical reaction that is
      based on the laser-induced breakdown of a nanoscopic barrier, which physically
      separates the reactants in space. Because the breakdown of the barrier is fast (
      approximately 0.3 micros) and owing to the nanometer dimension of the barrier,
      the reactants can be brought together and the reaction can be initiated rapidly.
      The time scale most suited for this method (from microseconds to tens of
      milliseconds) bridges nicely between the faster time scales that are accessible
      mostly with laser-based triggering experiments and the slower time scales that
      are studied most frequently with flow-based devices.

PMID- 15491173
TI  - Direct observation of the one-electron reduction of methyl viologen mediated by
      the CO2 radical anion during TiO2 photocatalytic reactions.
AB  - The one-electron reduction of methyl viologen (MV(2+)) mediated by the carbon
      dioxide radical anion (CO(2)(*-)) during photocatalytic reactions in a colloidal
      TiO(2) aqueous solution (pH 2) has been investigated by time-resolved absorption
      spectroscopy. The formation of MV(*+) generated from the one-electron reduction
      reaction with CO(2)(*-), which is generated from the one-electron oxidation
      reactions with the photogenerated holes (h(+)), was directly observed. The
      spectral features of the photogenerated charge carriers and the kinetic analysis
      of the formation process of MV(*+) revealed that the CO(2)(*-), desorbed from the
      surface, reacts with MV(2+) via a homogeneous electron-transfer process in the
      bulk solution.

PMID- 15491174
TI  - About the role of water in surface-grafted poly(ethylene glycol) layers.
AB  - We focus on the role of water in a protein-resistant poly(ethylene glycol) (PEG)
      layer. Using the combination of two experimental techniques, namely, the extended
      surface forces apparatus and the quartz crystal microbalance, we demonstrate that
      the water content inside these surface-grafted layers is over 80 vol % while the
      conformational space of the PEG chains is significantly modulated in water.
      Discrete and reversible film thickness transitions of 1.25 A size are shown to
      occur when the film is compressed, a finding that suggests a high degree of
      organization in the PEG/water complex. The results are discussed in terms of the
      excellent protein resistance properties of this type of surface.

PMID- 15491175
TI  - Gelatin microemulsion-based gels with the cationic surfactant
      cetyltrimethylammonium bromide: a self-diffusion and conductivity study.
AB  - In this contribution we demonstrate that gelatin can jellify also water-in-oil
      microemulsions based on the cationic surfactant cetyltrimethylammonium bromide
      (CTAB). The partial stability diagram of the system CTAB + 1-pentanol + water +
      hexane + gelatin was determined. The resulting microemulsion-based gels (MBGs)
      were characterized by means of conductivity and pulsed gradient spin-echo NMR.
      For the first time the water self-diffusion coefficient was measured in gelatin
      MBGs, and the results were successfully analyzed in terms of diffusion in an
      interconnected network of aqueous channels.

PMID- 15491176
TI  - Redox chemistry of Cu colloids probed by adsorbed CO: an in situ attenuated total
      reflection Fourier transform infrared study.
AB  - The IR spectroscopic investigation of both the adsorption of carbon monoxide and
      the interaction of oxygen and CO on the surface of copper colloids is described
      for the first time. The copper colloids were produced by pyrolysis of
      [Cu(OCH(Me)CH(2)NMe(2))(2)] in hot n-hexadecylamine. Upon contact to synthetic
      air Cu/Cu(x)O core-shell particles are formed. The treatment of these particles
      with CO results in the reestablishment of pure Cu(0) particles. These results
      demonstrate that small molecules penetrate the ligand shell of the nanoparticles
      and reversibly adsorb at the surface without affecting the particle morphology
      and size distribution.

PMID- 15491177
TI  - Zirconium hydrocarbyl chemisorption on sulfated metal oxides: new supports,
      chemisorption pathways, and implications for catalysis.
AB  - The sulfated metal oxides (SMOs) sulfated stannia (SnS), sulfated iron oxide
      (FeS), and sulfated titanium dioxide (TiS) have been synthesized and examined as
      support materials/cocatalysts/activators for molecule-based olefin polymerization
      and hydrogenation catalysis. (13)C CPMAS NMR spectroscopic analysis of
      Cp(2)Zr((13)CH(3))(2)/SMO chemisorption shows that cationic zirconocenium species
      are formed along with varying amounts of catalytically inactive micro-oxo
      (Cp(2)Zr(CH(3))O-surface) species, depending on the support material. Ethylene
      polymerization data with the supported catalysts show that polymerization
      activity is dependent on both precursor ligation [Zr(CH(2)Ph)(4) >
      (Me(5)Cp)ZrMe(3)] and the nature of the support (SnS > FeS > TiS). Poisoning
      studies were performed in conjunction with ethylene polymerization, mediated by
      (Me(5)Cp)ZrMe(3) supported on each SMO, and reveal that, for
      (Me(5)Cp)ZrMe(3)/SnS, 61 +/- 5% of the Zr sites are catalytically significant,
      while, for (Me(5)Cp)ZrMe(3)/FeS, this quantity is 22 +/- 2%, and for
      (Me(5)Cp)ZrMe(3)/TiS, 63 +/- 9%. These catalysts are also active for benzene
      hydrogenation and are separable from liquid-phase products using physical or, in
      the case of FeS, magnetic techniques.

PMID- 15491178
TI  - Mechanisms of foam destruction by oil-based antifoams.
AB  - Oils and mixtures of oils with hydrophobic particles are widely used in various
      technologies and consumer products to control foaminess and foam stability. The
      aim of this review is to summarize our current understanding of the mechanisms of
      foam destruction by such substances, which are usually called antifoams or
      defoamers. The experimental results show that two types of antifoam can be
      distinguished (called for brevity "fast" and "slow") which differ in the modes of
      their action. Fast antifoams are able to rupture the foam films at the early
      stages of film thinning. As a result, fast antifoams destroy completely the foam
      in less than a minute, in a typical foam-stability test. Microscopic observations
      have shown that the fast antifoams rupture the foam films by the so-called
      "bridging" mechanisms, which involve the formation of oil bridges between the two
      surfaces of the foam film. The stability/instability of these oil bridges is
      explained by using the theory of capillarity. In contrast, the oily globules of
      the slow antifoams are unable to enter the surfaces of the foam films and are
      first expelled into the Plateau borders (PBs). Only after being compressed by the
      narrowing walls of the PBs (due to water drainage from the foam), are the
      globules of the slow antifoams able to enter the solution surface and to destroy
      the adjacent foam films. Typically, the process of foam destruction by slow
      antifoams requires much longer time, minutes or tens of minutes, and a residual
      foam of well-defined height is observed in the foam tests. The experiments show
      that there is no direct relation between the magnitudes of the entry, E,
      spreading, S, and bridging, B, coefficients, on one side, and the antifoam
      efficiency, on the other side. The only requirement for having active antifoam,
      with respect to the bridging mechanisms, is that B should be positive. On the
      other hand, the barrier preventing the emergence of pre-emulsified antifoam
      globules on the solution surface (so-called "entry barrier") is of crucial
      importance for the mode of foam destruction and for the antifoam efficiency.
      Measurements of the entry barrier with recently developed film trapping technique
      (FTT) showed that antifoams possessing low entry barriers act as fast antifoams,
      whereas high barriers correspond to slow or inactive antifoams, although E, S,
      and B coefficients could be strongly positive in the latter case. A good
      agreement between the magnitude of the entry barrier, measured by FTT, and the
      height of the residual foam, in the presence of slow antifoams, was
      experimentally established and theoretically explained. The importance of various
      factors, such as the size of antifoam globules, oil spreading, kinetics of
      surfactant adsorption, hydrophobicity of solid particles in mixed oil-solid
      antifoams, and the presence of amphiphilic additives (foam boosters), is
      discussed from the viewpoint of the mechanisms of antifoaming. The main
      experimental methods, used for studying the modes of antifoam action, are briefly
      described.

PMID- 15491179
TI  - Calorimetric study on the temperature dependence of the formation of mixed
      ionic/nonionic micelles.
AB  - The differential excess enthalpy of mixed micelle formation was measured at
      different temperatures by mixing nonionic hexa(ethylene glycol) mono n-dodecyl
      ether with anionic sodium dodecyl sulfate or cationic dodecylpyridinium chloride.
      The experimental data were obtained calorimetrically by titrating a concentrated
      surfactant solution into a micellar solution of nonionic surfactant. The
      composition and the size of the mixed nonionic/ionic micelles at different
      surfactant concentrations were also determined. Pronounced differences in both
      composition and excess enthalpy were found between the anionic and the cationic
      mixed system. For both systems, the excess enthalpies become more exothermic with
      increasing temperature, but for the anionic mixed system an additional exothermic
      contribution was found which was much less temperature dependent. Temperature
      dependence of the excess enthalpy was attributed to the effect of the ionic
      headgroup on the hydration of the ethylene oxide (EO) groups in the mixed corona.
      Ionic headgroups located in the ethylene oxide layer cause the dehydration of the
      EO chains resulting in an additional hydrophobic contribution to the enthalpy of
      mixing. A high affinity of sodium dodecyl sulfate for nonionic micelles and an
      extra exothermic and less temperature dependent contribution to the excess
      enthalpy found for the SDS-C(12)E(6) system might be attributed to specific
      interactions (hydrogen bonds) between the sulfate headgroup and the partly
      dehydrated EO chain.

PMID- 15491180
TI  - Molecular aggregation of disklike benzenetricarboxamides containing diacetylenic
      groups in bulk and organic solvents.
AB  - We prepared disklike tris(4-alkylbutadiynylphenyl)-1,3,5-benzenetricarboxamide
      and tris[4-(4-alkyloxyphenyl)butadiynylphenyl]-1,3,5-benzenetricarboxamide, where
      three phenyl diacetylenic and diphenyl diacetylenic groups are connected to a
      benzene ring through amide linkages, respectively. The structures of self
      assembled substances were investigated by using transmission electron microscopy,
      scanning electron microscopy, and X-ray diffraction techniques. All the compounds
      were highly viscous in melt states, and only compound 9 having three phenyl
      diacetylenic groups and hexyl tails showed a thermotropic mesophase on cooling.
      The compound with three diphenyl diacetylenic groups and dodecyloxy tails (13)
      formed a stable gel in THF/cyclohexane. The IR and X-ray analyses showed that in
      the gel state molecules were assembled into a rectangular columnar lattice and
      held each other by hydrogen bondings between amide groups. The compound with
      tetradecyloxy tails (14) formed stable colloidal particles in cyclohexane. The UV
      irradiation of 13 in a gel and 14 in a colloidal particle did not result in a
      long conjugated polymer because of the inappropriate alignment of diacetylenic
      groups for the topochemical polymerization.

PMID- 15491181
TI  - Crust effect on multiscale pattern formations in drying micelle solution drops on
      solid substrates.
AB  - Spherical micelles of a polystyrene-b-poly(dimethylsiloxane) (PS-b-PDMS) diblock
      copolymer with the number-average molecular weight of 193 000 g/mol for PS and 39
      000 g/mol for PDMS were obtained by using n-dodecane or n-octane as the selective
      solvent for the PDMS block. The drying process of micelle solution drops with
      relatively high polymer concentration on solid substrates and the resultant
      drying patterns were studied using optical microscopy and atomic force
      microscopy. The drying drops exhibited an inner solution "cap" connecting with an
      outer gelled "foot" through a transition zone. A crust was first formed on the
      surface of the transition zone and remained on the top of the foot region. An
      inhomogeneous stress perpendicular to the radial direction within the crust,
      which was due to the solvent evaporation accompanied by the receding of the
      solution cap, induced regular 45 degrees -tilted stripes (pleats) in the
      transition zone and main radial cracks in the foot region. The stripes and cracks
      have periods of a few and tens of microns, respectively. Concave micelle "bricks"
      were also observed between cracks. In addition to micelle close packing, these
      patterns demonstrate that drying micelle solution drops may provide a potential
      means to manipulate fine and multiscale structures for technological
      applications.

PMID- 15491182
TI  - Shape changes and vesicle fission of giant unilamellar vesicles of liquid-ordered
      phase membrane induced by lysophosphatidylcholine.
AB  - Liquid-ordered phase (lo phase) of lipid membranes has properties that are
      intermediate between those of liquid-crystalline phase and those of gel phase and
      has attracted much attention in both biological and biophysical aspects. Rafts in
      the lo phase in biomembranes play important roles in cell function of mammalian
      cells such as signal transduction. In this report, we have prepared giant
      unilamellar vesicles (GUVs) of lipid membranes in the lo phase and investigated
      their physical properties using phase-contrast microscopy and fluorescence
      microscopy. GUVs of dipalmitoyl-phosphatidylcholine (DPPC)/cholesterol membranes
      and also GUVs of sphingomyelin (SM)/cholesterol membranes in the lo phase in
      water were formed at 20-37 degrees C successfully, when these membranes contained
      >/=30 mol % cholesterol. The diameters of GUVs of DPPC/cholesterol and
      SM/cholesterol membranes did not change from 50 to 28 degrees C, supporting that
      the membranes of these GUVs were in the lo phase. To elucidate the interaction of
      a substance with a long hydrocarbon chain with the lo phase membrane, we
      investigated the interaction of low concentrations (less than critical micelle
      concentration) of lysophosphatidylcholine (lyso-PC) with DPPC/cholesterol GUVs
      and SM/cholesterol GUVs in the lo phase. We found that lyso-PC induced several
      shape changes and vesicle fission of these GUVs above their threshold
      concentrations in water. The analysis of these shape changes indicates that lyso
      PC can be partitioned into the external monolayer in the lo phase of the GUV from
      the aqueous solution. Threshold concentrations of lyso-PC in water to induce the
      shape changes and vesicle fission increased greatly with a decrease in chain
      length of lyso-PC. Thermodynamic analysis of this result indicates that shape
      changes and vesicle fission occur at threshold concentrations of lyso-PC in the
      membrane. These new findings on GUVs of the lo phase membranes indicate that
      substances with a long hydrocarbon chain such as lyso-PC can enter into the lo
      phase membrane and also the raft in the cell membrane. We have also proposed a
      mechanism for the lyso-PC-induced vesicle fission of GUVs.

PMID- 15491183
TI  - Colloid stability of lipid/polyelectrolyte decorated latex.
AB  - The colloid stability of supramolecular assemblies composed of the synthetic
      cationic lipid dioctadecyldimethylammonium bromide (DODAB) on carboxymethyl
      cellulose (CMC) supported on polystyrene amidine (PSA) microspheres was evaluated
      via turbidimetry kinetics, dynamic light scattering for particle sizing, zeta
      potential analysis, and determination of DODAB adsorption on CMC-covered
      particles. At 0.1 g L(-1) CMC and 2 x 10(11) PSA particles/mL, CMC did not induce
      significant particle flocculation, and a vast majority of CMC-covered single
      particles were present in the dispersion so that this was the condition chosen
      for determining DODAB concentration (C) effects on particle size and zeta
      potentials. At 0.35 mM DODAB, charge neutralization, maximal size, and visible
      precipitation indicated extensive flocculation and minimal colloid stability for
      the DODAB/CMC/PSA assembly. At 0.1 g L(-1) CMC, isotherms of high affinity for
      DODAB adsorption on CMC-covered particles presented a plateau at a limiting
      adsorption of 700 x 10(17) DODAB molecules adsorbed per square meter PSA which
      was well above bilayer deposition on a smooth particle surface. The
      polyelectrolyte layer on hydrophobic particles was swelled and fluffy (ca. 11-nm
      hydrodynamic thickness), and maximal adsorption of DODAB lipid onto this layer
      produced a compressed composite cationic film with 20 mV of zeta potential and
      about 10-nm mean thickness. The assembly of cationic lipid/CMC layer/polymeric
      particle was stable only well above charge neutralization of the polyelectrolyte
      by the cationic lipid, at relatively large lipid concentrations (at and above 1
      mM DODAB) with charge neutralization leading to extensive particle aggregation.

PMID- 15491184
TI  - Growth and scission energy of wormlike micelles formed by a cationic surfactant
      with long unsaturated tails.
AB  - The structural and dynamic properties of micellar solutions of erucyl
      bis(hydroxyethyl)methylammonium chloride blended with 2-propanol, in the presence
      of KCl, have been investigated by means of light scattering and rheological
      experiments. In the dilute regime, the micellar growth is larger than expected
      from mean-field or scaling models. The results obtained in the vicinity of the
      overlap concentration suggest the presence of large aggregates, with size >100
      nm, possibly micellar rings or microgels. In the semidilute regime, the
      relationship between the zero shear viscosity and the surfactant concentration is
      described by a power law with an exponent in agreement with the mean-field model
      of linear micelles. The methods based on the analysis of the temperature
      dependence of the complex shear modulus to provide a measure of the scission
      energy are discussed.

PMID- 15491185
TI  - Thermodynamics of micellization of benzyl(2-acylaminoethyl)dimethylammonium
      chloride surfactants in aqueous solutions: a conductivity and titration
      calorimetry study.
AB  - The enthalpies of micellization of the surfactant series benzyl(2
      acylaminoethyl)dimethylammonium chlorides, RABzMe(2)Cl, have been determined by
      calorimetry and conductivity measurements in the temperature range 15-75 degrees
      C. Here R stands for an acyl group containing 10-16 carbon atoms and A, Bz, and
      Me stand for NH(CH(2))(2)N(+), benzyl, and methyl groups, respectively. The
      enthalpy of micellization, DeltaH(mic) degrees , and the critical micelle
      concentration, cmc, were calculated directly from calorimetric data. The free
      energy of micellization, DeltaG(mic) degrees , was obtained from the cmc and the
      conductance-based degree of counterion dissociation. There is an excellent
      agreement between DeltaG(mic) degrees calculated from the data of both
      techniques, but the DeltaH(mic) degrees , the entropy of micellization, values
      differ. The dependence of the thermodynamic parameters of micellization on the
      chain length of the hydrophobic group and on the temperature has been analyzed by
      considering the delicate balance between the factors that contribute to micelle
      formation, including transfer of the surfactant hydrocarbon chain from the
      aqueous environment to the micelle, with concomitant release of the solvating
      water molecules, and the effect of temperature on the structure of water.
      DeltaG(mic) degrees is more negative, that is, more favorable for RABzMe(2)Cl
      than for the structurally related alkylbenzyldimethylammonium chlorides. This is
      attributed to direct and water-mediated H bonding between the amide groups of
      molecules of the former series.

PMID- 15491186
TI  - Diffusion of molecules confined in semipenetrable nanoscale carriers probed by
      pulsed field gradient NMR.
AB  - Diffusion of three low-molecular-weight compounds cyclohexane (CX), benzene (BZ),
      and chloroform (CL) preferentially confined in the cores of nanoscale carriers
      was probed by pulsed field gradient (PFG) NMR methods. The carriers were
      monolayer micelles of sodium dodecyl sulfate (SDS), bilayer micelles of
      poly(hexyl methacrylate)-block-(acrylic acid) (M2), and trilayer micelles of
      poly(2-ethylhexyl methacrylate)-block-(methyl methacrylate)-block-(acrylic acid)
      (M3) in D(2)O at 300 K. Although the radius of the confinement space was 10(-)(8)
      m or lower, the course of the PFG signal attenuation in pulsed gradient spin-echo
      or stimulated echo experiments under varied diffusion time corresponds to
      apparently unrestricted diffusion, which is slowed down compared to that of the
      compound dissolved in D(2)O. Analysis using approximate relations reveals that
      the response of the system to PFG NMR consists of three independent components,
      namely (i) diffusion of the carrier as a whole, (ii) hindered escape of a
      confined molecule and its diffusion in the medium, and (iii) diffusion of the
      molecules dissolved in the medium. If process ii is fast enough, exchange of the
      compound between the carrier and the medium includes the influence of iii as a
      component of a monoexponential PFG decay; otherwise, two sets of signals are
      observed with different diffusion responses, or biexponential PFG is observed.
      According to the results of this study, the only barrier of the diffusion of the
      inspected compounds CX, BZ, and CL out of their confinement in the carriers SDS
      or M2 is a thermodynamic one, that is, the resistance of the saturated solution
      to accept surplus molecules of the solute. In a three-layer micelle M3, the
      additional polymer sheet around the confinement area forms an additional
      diffusion barrier for CX, however. The study shows that PFG NMR, though unable to
      observe directly restricted diffusion on the nanoscale, can be useful in studying
      systems designed, for example, for a controlled release of low-molecular-weight
      substances.

PMID- 15491187
TI  - Influence of iota-carrageenan on droplet flocculation of beta-lactoglobulin
      stabilized oil-in-water emulsions during thermal processing.
AB  - The influence of thermal processing on droplet flocculation in oil-in-water
      emulsions stabilized by either beta-lactoglobulin (primary emulsions) or beta
      lactoglobulin-iota-carrageenan (secondary emulsions) at pH 6 has been
      investigated. In the absence of salt, the zeta-potential of the primary emulsion
      was less negative (-40 mV) than that of the secondary emulsion (-55 mV) due to
      adsorption of anionic iota-carrageenan to the anionic beta-Lg-coated droplet
      surfaces. The zeta-potential and mean diameter (d(43) approximately 0.3 microm)
      of droplets in primary and secondary emulsions did not change after storage at
      temperatures ranging from 30 to 90 degrees C. In the presence of 150 mM NaCl, the
      zeta-potential of the primary emulsion was much less negative (-27 mV) than that
      of the secondary emulsion (-50 mV), suggesting that the latter was less
      influenced by electrostatic screening effects. The zeta-potential of the primary
      emulsions did not change after storage at elevated temperatures (30-90 degrees
      C). The zeta-potential of the secondary emulsions became less negative, and the
      aqueous phase iota-carrageenan concentration increased at storage temperatures
      exceeding 50 degrees C, indicating iota-carrageenan desorbed from the beta-Lg
      coated droplets. In the primary emulsions, appreciable droplet flocculation
      (d(43) approximately 8 microm) occurred at temperatures below the thermal
      denaturation temperature (T(m)) of the adsorbed proteins due to surface
      denaturation, while more extensive flocculation (d(43) > 20 microm) occurred
      above T(m) due to thermal denaturation. In the secondary emulsions, the extent of
      droplet flocculation below T(m) was reduced substantially (d(43) approximately
      0.8 microm), which was attributed to the ability of adsorbed carrageenan to
      increase droplet-droplet repulsion. However, extensive droplet flocculation was
      observed above T(m) because carrageenan desorbed from the droplet surfaces.
      Differential scanning calorimetry showed that iota-carrageenan and beta-Lg
      interacted strongly in aqueous solutions containing 0 mM NaCl, but not in those
      containing 150 mM NaCl, presumably because salt weakened the electrostatic
      attraction between the molecules.

PMID- 15491188
TI  - Use of the JKR model for calculating adhesion between rough surfaces.
AB  - A simple method for using the JKR model to determine interfacial adhesion between
      two ideal rough surfaces is demonstrated for individual asperity-asperity and
      asperity-flat contacts both in air and in water. The model takes into account the
      effect of a modified contact area at separation due to viscoelastic effects. The
      equilibrium version of the model significantly underestimates the measured
      adhesion, whereas the viscoelastic version of the model is much closer to the
      measured data. The asperity-flat geometry used with the viscoelastic version of
      the model seems to fit the experimental results best. This was thought to be due
      to the unlikely occurrence of direct asperity-asperity contacts. Instead, it
      would seem that the asperities have a far higher chance of fitting between each
      other on opposing surfaces, leading to correspondingly higher pull-off forces
      measured on separation. Many possible extensions to the roughness model described
      here may be made, allowing a much-improved understanding of the contact mechanics
      between two rough surfaces.

PMID- 15491189
TI  - 13C NMR characterization of the organic constituents in ligand-modified hexagonal
      mesoporous silicas: media for the synthesis of small, uniform-size gold
      nanoparticles.
AB  - This paper reports the (13)C NMR characterization of functionalized MCM-41's and
      describes the chemistry that occurs in the pores of these materials in the
      process of forming gold nanoparticles. Nanoparticles formed on hexagonal
      mesoporous silica (MCM-41) by hydrogen reduction of chloroauric acid have little
      affinity for pure silica surfaces. The gold can be removed from the support with
      very mild treatment, for example, solvent extraction. The loss of gold from the
      substrate can be prevented using a pore functionalization methodology that
      entails synthesis of the silica containing polydentate amine functionality
      chemically bound in the mesopores. The synthetic scheme introduces solvents and
      templating reagents (surfactants) into the mesopores that are chemically reactive
      under the conditions required for gold particle formation. Extensive base
      catalyzed elimination and nucleophilic substitution reactions involving the
      tetraalkylammonium surfactant occur during the reduction of chloroauric acid to
      gold.

PMID- 15491190
TI  - Adsorption of cadmium on anatase nanoparticles-effect of crystal size and pH.
AB  - The adsorption and desorption of Cd(2+) to large and nanometer-scale anatase
      crystals have been studied to determine the relationship between heavy metal
      adsorption properties and anatase particle size. A solvothermal method was used
      to synthesize very fine anatase nanocrystals with average grain sizes ranging
      from 8 to 20 nm. On a surface area basis, it was found that large and nanometer
      scale anatase particles had similar maximum Cd(2+) adsorption capacities, while
      their adsorption slopes differed by more than 1 order of magnitude. The particle
      size effect on adsorption is constant over a pH range of 4-7.5. The desorption of
      Cd(2+) from both particle sizes is completely reversible. The adsorption data
      have been modeled by the Basic Stern model using three monodentate surface
      complexes. It is proposed that intraparticle electrostatic repulsion may reduce
      the adsorption free energy significantly for nanometer-sized particles.

PMID- 15491191
TI  - Contact angles of colloid silica and gold particles at air-water and oil-water
      interfaces determined with the gel trapping technique.
AB  - We have used the recently developed gel trapping technique (GTT) to determine the
      three-phase contact angles of submicrometer silica particles partially coated
      with octadecyl groups. The particles were spread at air-water and decane-water
      surfaces, and the aqueous phase was subsequently gelled with a nonadsorbing
      polysaccharide. The particles trapped at the surface of the aqueous gel were
      lifted by molding with curable poly(dimethylsiloxane) and imaged with scanning
      electron microscopy (SEM) to determine the particle contact line diameter which
      allows their contact angle at the original air-water or oil-water interface to be
      estimated. We report for the first time the use of the GTT for characterizing the
      contact angle of individual submicrometer particles adsorbed at liquid
      interfaces. The SEM images also reveal the structure of the particle monolayer at
      the interface and the structure of adsorbed particle aggregates. We have also
      determined the contact angles of agglomerated gold powder microparticles at the
      air-water and the decane-water interfaces. It was found that agglomerated gold
      particles demonstrate considerably higher contact angles than those on flat gold
      coated surfaces.

PMID- 15491192
TI  - Multilayer assembly and patterning of poly(p-phenylenevinylene)s via covalent
      coupling reactions.
AB  - Poly(p-phenylenevinylene)s with amines and pentafluorophenyl esters on side
      chains were synthesized and assembled on solid substrates by sequential layer-by
      layer (LBL) deposition. This approach enables the creation of robust multilayer
      thin films via in-situ covalent coupling reactions between successive layers. The
      buildup of the multilayers was followed by UV/vis absorption spectroscopy and
      ellipsometry. The observed complex assembly behavior suggests that both covalent
      and hydrogen-bonding interactions are involved in the formation of multilayer
      films. The organized structure and surface morphology of resultant multilayers
      were investigated by reflectance Fourier transform infrared spectroscopy, X-ray
      photoelectron spectroscopy, and atomic force microscopy. This covalent LBL method
      was further applied to generate conjugated polymer micropatterns using
      microstamped self-assembled monolayers as templates.

PMID- 15491193
TI  - A simple approach to micropatterning and surface modification of
      poly(dimethylsiloxane).
AB  - Ozone treatment is an efficient economical, alternative method for surface
      activation of poly(dimethylsiloxane) (PDMS). This is illustrated by the
      derivatization of a PDMS surface with (3-aminopropyl)triethoxysilane (APTES). The
      apparent surface concentration of amino groups was found to be ca. 10(-8) mol/cm2
      using UV/visible spectroscopy of the product from the reaction of the amino
      groups and fluorescamine. Potential application for micropatterning of
      biologically active interfaces was demonstrated by the covalent immobilization of
      oligonucleotides. A simple process for photolithographic patterning on PDMS
      surfaces has been developed.

PMID- 15491194
TI  - High-pressure adsorption capacity and structure of CO2 in carbon slit pores:
      theory and simulation.
AB  - We present new simulation results for the packing of single-center and three
      center models of carbon dioxide at high pressure in carbon slit pores. The former
      shows a series of packing transitions that are well described by our density
      functional theory model developed earlier. In contrast, these transitions are
      absent for the three-center model. Analysis of the simulation results shows that
      alternations of flat-lying molecules and rotated molecules can occur as the pore
      width is increased. The presence or absence of quadrupoles has negligible effect
      on these high-density structures.

PMID- 15491195
TI  - X-ray photoelectron spectroscopy and differential capacitance study of thiol
      functional polysiloxane films on gold supports.
AB  - Polymeric molecules containing multiple thiol groups (polythiols) provide
      tenacious attachment to metal surfaces such as gold. Polythiol films are also
      well suited for subsequent derivatization with biomacromolecules through remnant
      free thiol groups of the film. In this study, 1-3 nm thick layers of a commercial
      polythiol, poly((mercaptopropyl)methylsiloxane) (PMPMS), are investigated with X
      ray photoelectron spectroscopy (XPS) and electrochemical impedance spectroscopy.
      XPS is used to reveal the surface coverage of thiolate-Au bonds between the
      polythiol and the metal support, which is found to be approximately 30% lower
      than that in alkanethiol self-assembled monolayers. The surface density of
      thiolate-Au bonds did not depend on film thickness provided sufficient PMPMS
      material was present. Differential capacitance measurements show that the
      effective dielectric barrier presented by PMPMS films under aqueous environments
      corresponds closely to their physical thickness, with even approximately 1 nm
      films remaining impermeable to electrolyte species. Modification of the films
      with an oligoethylene glycol compound was also examined, in anticipation of
      future applications in label-free, impedance-based biomolecular diagnostics.

PMID- 15491196
TI  - A nanoscale view of supramolecular stereochemistry in self-assembled monolayers
      of enantiomers and racemates.
AB  - The effect that molecular chirality has on the formation of monolayer structures
      by pure enantiomers and their racemates at the liquid/solid interface has been
      investigated for two chiral compounds (1 and 2) which differ from each other by
      the presence or absence of an ester function in their respective molecular
      structures. 1 shows pseudoracemate formation when the achiral graphite support is
      exposed to a solution containing a racemate while 2 shows racemic conglomerate
      formation. This difference is rationalized in terms of the orientation of the
      pure enantiomers with respect to the graphite substrate and highlights the
      importance of molecular structure and its influence on balancing the interplay
      between molecular conformation and molecular packing on the surface. For 1,
      nonstoichiometric mixtures of both enantiomers have been investigated, and the
      results are discussed in the framework of the sergeant and soldiers principle.
      These results are important for the understanding and prediction of spontaneous
      resolution in monolayer systems.

PMID- 15491197
TI  - Oxidation of alkylsilane-based monolayers on gold.
AB  - The oxidation of alkylsilane monolayers on Au has been studied by X-ray
      photoelectron spectroscopy, reflection-absorption infrared spectroscopy, contact
      angle measurements, and scanning tunneling microscopy. Exposure of the monolayers
      at 298 K to pure O(2) or H(2)O (>5 x 10(-5) Torr and >150 000 L) does not cause
      oxidation. Ambient atmosphere only causes oxidation if direct sight lines are
      maintained to the sample. Ozone exposure results in rapid monolayer oxidation.
      Oxidation initially occurs only at the Si atom, resulting in formation of a cross
      linked siloxane monolayer that retains alkyl surface termination. Prolonged ozone
      exposures result in the oxidation and subsequent loss of the alkyl chain.

PMID- 15491198
TI  - Single and multicomponent equilibrium studies for the adsorption of acidic dyes
      on carbon from effluents.
AB  - The ability of activated carbon to adsorb three acidic dyes, namely, Acid Blue 80
      (AB80), Acid Red 114 (AR114), and Acid Yellow (AY117), from wastewater has been
      studied at 20 degrees C. The three single-component systems and the three binary
      equilibrium systems have been measured experimentally. The three single-component
      isotherms were analyzed using the Langmuir, Freundlich, Redlich-Peterson, and
      Sips equations. The Redlich-Peterson equation gave the lowest errors using the
      sum of the squares of the errors closely followed by the Sips and Langmuir
      equations; the Freundlich fits were significantly worse. The three bisolute
      experimental equilibrium sets of data were analyzed by incorporating the previous
      four single-component isotherm equations into the ideal adsorbed solution theory
      (IAST). The solution methods for each of the four isotherm equations are
      presented in the paper, and the predicted results for the three bisolute systems,
      using the four isotherm equations, are compared. For the three bisolute systems
      (AB80 + AR114, AB80 + AY117, and AR114 + AY117), the Redlich-Peterson isotherm
      gives the best correlation with the experimental isotherm data.

PMID- 15491199
TI  - Effect of surfactants on wetting of super-hydrophobic surfaces.
AB  - The effect of surfactants on wetting behavior of super-hydrophobic surfaces was
      investigated. Super-hydrophobic surfaces were prepared of alkylketene dimer (AKD)
      by casting the AKD melt in a specially designed mold. Time-dependent studies were
      carried out, using the axisymmetric drop shape analysis method for contact angle
      measurement of pure water on AKD surfaces. The results show that both advancing
      and receding contact angles of water on the AKD surfaces increase over time (
      approximately 3 days) and reach the values of about 164 and 147 degrees ,
      respectively. The increase of contact angles is due to the development of a
      prickly structure on the surface (verified by scanning electron microscopy),
      which is responsible for its super-hydrophobicity. Aqueous solutions of sodium
      acetate, sodium dodecyl sulfate, hexadecyltrimethylammonium bromide, and n
      decanoyl-n-methylglucamine were used to investigate the wetting of AKD surfaces.
      Advancing and receding contact angles for various concentrations of different
      surfactant solutions were measured. The contact angle results were compared to
      those of a number of pure liquids with surface tensions similar to those of
      surfactant solutions. It was found that although the surface tensions of pure
      liquids and surfactant solutions at high concentrations are similar, the contact
      angles are very different. Furthermore, the usual behavior of super-hydrophobic
      surfaces that turn super-hydrophilic when the intrinsic contact angle of liquid
      on a smooth surface (of identical material) is below 90 degrees was not observed
      in the presence of surfactants. The difference in the results for pure liquids
      and surfactant solutions is explained using an adsorption hypothesis.

PMID- 15491200
TI  - Nanomechanics of the formation of DNA self-assembled monolayers and hybridization
      on microcantilevers.
AB  - Biomolecular interactions over the surface of a microcantilever can produce its
      bending motion via changes of the surface stress, which is referred to
      nanomechanical response. Here, we have studied the interaction forces responsible
      for the bending motion during the formation of a self-assembled monolayer of
      thiolated 27-mer single-stranded DNA on the gold-coated side of a microcantilever
      and during the subsequent hybridization with the complementary nucleic acid. The
      immobilization of the single-stranded DNA probe gives a mean surface stress of 25
      mN/m and a mean bending of 23 nm for microcantilevers with a length and thickness
      of about 200 microm and 0.8 microm, respectively. The hybridization with the
      complementary sequence could not be inferred from the nanomechanical response.
      The nanomechanical response was compared with data from well-established
      techniques such as surface plasmon resonance and radiolabeling, to determine the
      surface coverage and study the intermolecular forces between neighboring DNA
      molecules anchored to the microcantilever surface. From both techniques, an
      immobilization surface density of 3 x 10(12) molecules/cm(2) and a hybridization
      efficiency of 40% were determined. More importantly, label-free hybridization was
      clearly detected in the same conditions with a conventional sensor based on
      surface plasmon resonance. The results imply that the nanomechanical signal
      during the immobilization process arises mainly from the covalent attachment to
      the gold surface, and the interchain interactions between neighboring DNA
      molecules are weak, producing an undetectable surface stress. We conclude that
      detection of nucleic acid hybridization with nanomechanical sensors requires
      reference cantilevers to remove nonspecific signals, more sensitive
      microcantilever geometries, and immobilization chemistries specially addressed to
      enhance the surface stress variations.

PMID- 15491201
TI  - Dynamic surface properties of poly(N-isopropylacrylamide) solutions.
AB  - The dynamic surface elasticity of aqueous solutions of poly(N
      isopropylacrylamide) (pNIPAM) has been measured by the oscillating barrier and
      capillary wave methods as a function of time and concentration. While the real
      and imaginary parts of the surface elasticity almost did not change with the
      concentration, their kinetic dependencies proved to be nonmonotonic. Simultaneous
      measurements of the film thickness and adsorbed amount by null-ellipsometry
      showed that the pNIPAM adsorption can be divided into two steps corresponding to
      the formation of a concentrated narrow region close to the air phase and a region
      of tails and loops protruding into the bulk liquid. The local maximum of the
      elasticity can be observed in the course of the first step when the adsorbed
      macromolecules do not form long loops and tails. The results are in agreement
      with recent data on the nonequilibrium surface properties of solutions of other
      nonionic homopolymers and the theory of dilational surface viscoelasticity.

PMID- 15491202
TI  - Release of a dye from hydrogen-bonded and electrostatically assembled polymer
      films triggered by adsorption of a polyelectrolyte.
AB  - The absorption of dyes within hydrogen-bonded and electrostatically assembled
      multilayers and subsequent release of the dyes from the films were studied in
      situ using FTIR-ATR. Multilayers were composed of poly(methacrylic acid), PMAA,
      and poly(ethylene oxide), PEO (hydrogen-bonded multilayers), or of PMAA and 22%
      quarternized copolymer of N-ethyl-4-vinylpyridium bromide and 4-vinylpyridine,
      Q22 (electrostatically stabilized multilayers). After multilayer deposition, the
      solution pH was changed to produce excess charge within the films. Dyes with
      charge opposite to the excess charge of the film (Rhodamine 6G for hydrogen
      bonded films or Bromophenol Blue for electrostatically assembled multilayers)
      were then allowed to absorb within multilayers. In both systems, the dyes were
      uniformly included within the films. The top layers largely affected the loading
      capacity of the multilayers, suggesting weaker binding of the dyes with the top
      layers. Dye release into a 0.01 M phosphate buffer was significantly smaller as
      compared to release in the presence of 0.05-0.5 mg/mL solutions of adsorbing
      polymers whose charge was the same as the excess charge within the films. We
      found that with the PMAA/PEO films, dye release did not depend on the
      concentration of polymer in solution, but was largely controlled by the amount of
      charge accumulated within the adsorbing polymer layer on the top of the film. For
      electrostatically stabilized PMAA/Q22 systems, dye release increased with
      increasing concentration of Q22 in solution, suggesting a significant
      contribution of the competition of solution species in the release mechanism. Our
      findings contribute to the understanding of interactions of small molecules with
      polymer multilayers and might have ramifications for novel applications of
      multilayer films as new materials for the controlled delivery of chemicals.

PMID- 15491203
TI  - Dimethyl methylphosphonate decomposition on Cu surfaces: supported Cu
      nanoclusters and films on TiO2(110).
AB  - The thermal decomposition of dimethyl methylphosphonate (DMMP), which is a
      simulant molecule for organophosphorus nerve agents, has been investigated on Cu
      clusters as well as on Cu films deposited on a TiO(2)(110) surface. Scanning
      tunneling microscopy studies were conducted to characterize the cluster sizes and
      surface morphologies of the deposited Cu clusters and films. Temperature
      programmed desorption experiments demonstrated that the surface chemistry of DMMP
      is not sensitive to the size of the Cu clusters over the range studied in this
      work. DMMP reaction on an annealed 40 monolayer Cu film resulted in the
      desorption of H(2), methane, methyl, formaldehyde, methanol, and molecular DMMP,
      and reaction on the small (4.4 +/- 0.9 nm diameter, 1.8 +/- 0.6 nm height) and
      large (10.7 +/- 1.9 nm diameter, 4.8 +/- 1.0 nm height) Cu clusters generated
      similar products. Formaldehyde and methane production is believed to occur via a
      methoxy intermediate on the Cu surface. These products are favored on the higher
      coverage Cu films that completely cover the TiO(2) surface since competing
      reaction pathways on TiO(2) are suppressed. X-ray photoelectron spectroscopy
      studies showed that DMMP begins to decompose on the Cu clusters upon adsorption
      at room temperature and that atomic carbon, atomic phosphorus, and PO(x) remain
      on the surface after DMMP decomposition.

PMID- 15491204
TI  - Effect of the iridium oxide thin film on the electrochemical activity of platinum
      nanoparticles.
AB  - The influence of the iridium oxide thin film on the electrocatalytic properties
      of platinum nanoparticles was investigated using the electro-oxidation of
      methanol and CO as a probe. The presence of the IrO(2) thin film leads to the
      homogeneous dispersion of Pt nanoparticles. For comparison, polycrystalline
      platinum and Pt nanoparticles dispersed on a Ti substrate in the absence of an
      IrO(2) layer (Ti/Pt) were also investigated in this study. Inverted and enhanced
      CO bipolar peaks were observed using an in situ electrochemical Fourier transform
      infrared technique during the methanol oxidation on the Pt nanoparticles
      dispersed on a Ti substrate. Electrochemical impedance studies showed that the
      charge transfer resistance was significantly lower for the Ti/IrO(2)/Pt electrode
      compared with that of the massive Pt and Ti/Pt nanoparticles. The presence of the
      IrO(2) thin film not only greatly increases the active surface area but also
      promotes CO oxidation at a much lower electrode potential, thus, significantly
      enhancing the electrocatalytic activity of Pt nanoparticles toward methanol
      electro-oxidation.

PMID- 15491205
TI  - Adsorption of charged macromolecules at a gold electrode.
AB  - Using an optical reflectometer with impinging-jet system, the adsorption from
      aqueous solution onto gold of three charged macromolecules has been studied: the
      strong linear-chain polyelectrolyte polyvinyl pyridine (PVP(+)), the fifth
      generation poly(propylene imine) dendrimer DAB-64, which has a pH-dependent
      charge and a relatively fixed shape, and the protein lysozyme, of which both the
      charge and the structure-stability are dependent on solution composition.
      Experimental conditions that have been varied include the adsorbate
      concentration, electrolyte concentration, pH, and externally applied potential
      across the gold/solution interface. Making use of the earlier established
      dependency of the double layer potential of the gold substrate on solution
      conditions and externally applied potential, the results of measurements as a
      function of pH and as a function of external potential control are compared. The
      total set of results enables us to draw conclusions with respect to the relative
      importance of electrostatic interactions for the adsorption process. PVP(+)
      adsorption follows the electric potential of the gold/solution interface and is
      further determined by a rather strong nonelectrostatic affinity between segments
      and surface. The adsorption behavior of DAB-64 is not quite understood, but
      electrostatic interactions with the gold surface seem to play a minor role. For
      lysozyme, surface-induced conformational changes dominate the adsorption process.
      The extent of spreading of the molecules decreases with increasing polarity of
      the surface, resulting in a minimum in adsorbed amount around the point of zero
      potential of the gold.

PMID- 15491206
TI  - Magnetoswitchable controlled hydrophilicity/hydrophobicity of electrode surfaces
      using alkyl-chain-functionalized magnetic particles: application for switchable
      electrochemistry.
AB  - Magnetic nanoparticles consisting of undecanoate-capped magnetite (average
      diameter approximately 4.5 nm; saturated magnetization, M(s), 38.5 emu g(-1)) are
      used to control and switch the hydrophobic or hydrophilic properties of the
      electrode surface. A two-phase system consisting of an aqueous buffer solution
      and a toluene phase that includes the suspended capped magnetic nanoparticles is
      used to control the interfacial properties of the electrode surface. The magnetic
      attraction of the functionalized particles to the electrode by means of an
      external magnet yields a hydrophobic interface that acts as an insulating layer,
      prohibiting interfacial electron transfer. The retraction of the magnetic
      particles from the electrode to the upper toluene phase by means of the external
      magnet generates a hydrophilic electrode that reveals effective interfacial
      electron transfer. The electron-transfer resistance and double-layer capacitance
      of the electrode surface upon the attraction and retraction of the functionalized
      magnetic particles to and from the electrode, respectively, by means of the
      external magnet were probed by Faradaic impedance spectroscopy (R(et) = 170 Omega
      and C(dl) = 40 microF sm(-2) in the hydrophilic state of the electrode and R(et)
      = 22 k Omega and C(dl) = 0.5 microF sm(-2) in the hydrophobic state of the
      interface). The magnetoswitchable control of the interface enables magnetic
      switching of the bioelectrocatalytic oxidation of glucose in the presence of
      glucose oxidase and ferrocene dicarboxylic acid to "ON" and "OFF" states.

PMID- 15491207
TI  - Structure of spin-coated lipid films and domain formation in supported membranes
      formed by hydration.
AB  - An atomic force and fluorescence microscopy investigation of the structure of
      spin-coated lipid films is presented. In the surface of the dry film, lipids are
      found to orient in a conformation where acyl chains are pointing outward while
      laterally the individual layers of the multilamellar film exhibit a dewetting
      pattern similar to what is found in polymer thin films. Hydration of the film in
      liquid water promotes detachment of bilayers from the surface while a single
      membrane remains on the mica substrate. This supported membrane is highly uniform
      and defect-free as compared to supported membranes prepared by conventional
      methods. It is further demonstrated that supported membranes of binary lipid
      mixtures prepared by this method exhibit gel-fluid domain coexistence in
      accordance with expectations from the phase diagrams.

PMID- 15491208
TI  - Influence of surfactants and antibody immobilization strategy on reducing
      nonspecific protein interactions for molecular recognition force microscopy.
AB  - Specific and nonspecific interactions between antibody-modified probes and
      substrate-immobilized proteins were monitored by atomic force microscopy (AFM).
      Probes were modified with anti-ovalbumin IgG antibodies immobilized in either an
      oriented or a random manner. The oriented immobilization of whole IgG was
      accomplished through the use of Protein A, and random immobilization was carried
      out with glutaraldehyde. Nonspecific interactions may lead to false detection of
      antibody-antigen binding events even when the antigen binding sites are properly
      positioned by an oriented immobilization strategy. Thus, nonionic and
      zwitterionic surfactants, including Tween 20, Tween 80, Triton X-100, and CHAPS,
      were evaluated to determine if nonspecific binding events could be reduced
      without compromising the desired specific antibody-antigen binding. Enzyme-linked
      immunosorbent assay and surface plasmon resonance assays were also employed to
      study antibody-antigen binding as a function of immobilization strategy and
      surfactant concentration. The data from these studies indicate that Protein A can
      be used to immobilize whole IgG onto AFM probes for force measurement experiments
      and that a surfactant is useful for improving the selectivity for such
      measurements.

PMID- 15491209
TI  - Morphology of dry lignins and size and shape of dissolved kraft lignin particles
      by X-ray scattering.
AB  - Lignin is a highly branched polymer consisting of phenylpropane units, and it is
      one of the ingredients of the supporting matrix in plant cell walls. The
      morphology of several lignins extracted from plant cell walls using different
      methods was studied by small-angle and ultra-small-angle X-ray scattering. A
      power-law type intensity was observed for the dry lignins, but on the basis of
      the power-law exponent the fractal approach often applied to lignins is not fully
      justified. However, the intensity of kraft lignin did show a power law with
      surface fractal dimension D(s) = 2.7 +/- 0.1. The specific surface area of the
      lignins ranged from about 0.5 to 60 m(2)/g with 20% relative accuracy. The radius
      of gyration was determined from small-angle X-ray scattering data for aqueous
      solutions of kraft lignin. The shape of the particles in NaCl and NaOH solutions
      was found to be elongated. The particles were about 1-3 nm thick, while the
      length (5-9 nm) depended on the solvent and on the lignin concentration. The size
      of these primary particles was approximately the same as the size of the pores in
      the fractal aggregates of the dry kraft lignin. Their size was determined to be
      about 3.5 nm.

PMID- 15491210
TI  - Human serum albumin adsorption on TiO2 from single protein solutions and from
      plasma.
AB  - In the present work, the adsorption of human serum albumin (HSA) on commercially
      pure titanium with a titanium oxide layer formed in a H(2)O(2) solution (TiO(2)
      cp) and on TiO(2) sputtered on Si (TiO(2) sp) was analyzed. Adsorption isotherms,
      kinetic studies, and work of adhesion determinations were carried out. HSA
      exchangeability was also evaluated. Surface characterization was performed by
      atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), and
      wettability studies. The two TiO(2) surfaces have very distinct roughnesses, the
      TiO(2) sp having a mean R(a) value 14 times smaller than the one of TiO(2) cp.
      XPS analysis revealed consistent peaks representative of TiO(2) on sputtered
      samples as well as on Ti cp substrate after 48 h of H(2)O(2) immersion. Nitrogen
      was observed as soon as protein was present, while sulfur, present in disulfide
      bonds in HSA, was observed for concentrations of protein higher than 0.30 mg/mL.
      The work of adhesion was determined from contact angle measurements. As expected
      from the surface free energy values, the work of adhesion of HSA solution is
      higher for the TiO(2) cp substrate, the more hydrophilic one, and lower for the
      TiO(2) sp substrate, the more hydrophobic one. The work of adhesion between
      plasma and the substrates assumed even higher values for the TiO(2) cp surface,
      indicating a greater interaction between the surface and the complex protein
      solutions. Adsorption studies by radiolabeling of albumin ((125)I-HSA) suggest
      that rapid HSA adsorption takes place on both surfaces, reaching a maximum value
      after approximately 60 min of incubation. For the higher HSA concentrations in
      solution, a multilayer coverage was observed on both substrates. After the
      adsorption step from single HSA solutions, the exchangeability of adsorbed HSA
      molecules by HSA in solution was evaluated. The HSA molecules adsorbed on TiO(2)
      sp seem to be more easily exchanged by HSA itself than those adsorbed on TiO(2)
      cp after 24 h. In contrast, after 72 h, nearly all the adsorbed albumin molecules
      effectively exchange with other albumin molecules.

PMID- 15491211
TI  - Adhesion of polyether-modified poly(acrylic acid) to mucin.
AB  - Pluronic-PAA, a thermogelling copolymer composed of side chains of poly(acrylic
      acid) (PAA) grafted onto a backbone of Pluronic copolymer, is of interest as a
      vehicle for the controlled release of compounds. An important feature of such a
      vehicle is its bioadhesive/mucoadhesive properties, which in the case of Pluronic
      PAA are significant due to the presence of the PAA side chains. An atomic force
      microscopy (AFM) method has been developed and utilized to investigate the
      interactions between a Pluronic-PAA-modified microsphere and mucous substrates.
      The bioadhesive force was successfully measured, and trends were observed under
      conditions of varying pH and ionic strength. Pluronic-PAA exhibits significant
      mucoadhesion over a range of pH values, with mucoadhesion being optimal at pH 4-5
      (adhesive force approximately 80 mN/cm(2)) and dropping sharply at higher pH, to
      a value of approximately 20 mN/cm(2) at pH 8. The mucoadhesive force decreased
      with increasing ionic strength, from a value of approximately 80 mN/cm(2) in
      0.025 M NaCl to approximately 25 mN/cm(2) in 1.0 M NaCl. These results have been
      interpreted in terms of the effect of changing pH and ionic strength on
      electrostatic interactions and swelling of the polymer and mucin layers.
      Tensiometric force measurements indicated that hydrophobic interactions, as well
      as hydrogen bonding and electrostatic interactions, were significant in the
      mucoadhesion of Pluronic-PAA copolymers. Experiments with a range of Pluronic-PAA
      copolymers with varying PPO contents in the Pluronic segments showed that
      increasing the overall PPO content increased the hydrophobicity of the polymer
      solutions. This was reflected in the increases in the advancing contact angles
      with the mucin layer, indicating that hydrophobic interactions play a role in the
      adhesion of Pluronic-PAA to mucin.

PMID- 15491212
TI  - Adhesion between giant vesicles and supported bilayers decorated with chelated E
      cadherin fragments.
AB  - Here, we present a study of adhesion between cadherin fragments using giant
      unilamellar vesicles and supported bilayers. These objects are partially made of
      nickel chelating lipids and are subsequently decorated with proteins bearing a
      6His tag. Initially, we observed their fixation and correct orientation by using
      a fluorescent protein, the green fluorescent protein (GFP)-6His. The adhesive
      behavior of E-cadherin functionalized giant vesicles and supported bilayers was
      studied as a function of the calcium concentration and of the protein
      functionality by reflection interference microscopy. We show that such a system
      retains specific cadherin-mediated adhesion and could be used to study the
      statics and dynamics of adhesive plaques as well as to gain insight into the
      fundamental mechanisms of cellular adhesion at the mesoscopic scale.

PMID- 15491213
TI  - Fabrication of microarrays on fused silica plates using the laser-induced
      backside wet etching method.
AB  - A novel approach in the fabrication of microarrays of dye and protein on fused
      silica plates using the laser-induced backside wet etching (LIBWE) technique is
      described. The surface of fused silica plates was initially precoated using
      trimethoxysilane self-assembled monolayers (SAMs) and then etched using the LIBWE
      method to obtain the desired microstructures on the plate surface. Using this
      technique, the SAMs on the nonirradiated areas were able to survive the LIBWE
      process and were used as templates for the subsequent deposition of dye molecules
      or proteins via chemical bonding or physical adsorption. In the case of fused
      silica plates precoated with fluorinated SAMs, the LIBWE method is used to remove
      the SAMs to expose the etched silica surfaces, on which a thin layer of pyranine
      molecules can be site-selectively deposited using an aqueous solution of
      pyranine. In another application, an ethanol solution of rhodamine 6G was
      preferentially deposited onto the nonirradiated areas. In yet another
      application, bovine serum albumin was preferentially deposited onto the laser
      irradiated areas; in this case, the fused silica plates were precoated with
      poly(ethylene oxide) SAMs. Interestingly, when an aqueous suspension of
      polystyrene (PS) microbeads was cast onto the fused silica precoated with the
      fluorinated SAMs, hexagonally close-packed PS microbeads were deposited into the
      etched cavities. Depositions of the dye, protein, and microbeads were confirmed
      by visualization using a fluorescence microscope and scanning electron
      microscope.

PMID- 15491214
TI  - Formation and photoluminescence of silver nanoparticles stabilized by a two-armed
      polymer with a crown ether core.
AB  - Silver nanoparticles were synthesized by the use of a two-armed polymer with a
      crown ether core [poly(styrene)]-dibenzo-18-crown-6-[poly(styrene)] based on the
      flexibility of the polymer chains and the complex effect of crown ether with
      Ag(+) and Ag. The size of silver nanoparticles could be tailored by controlling
      the initial concentrations of the polymer and Ag(+), and the molecular weight of
      the polymer. The emission of silver nanoparticles was blue-shifted, and the
      intensity of the photoluminescence of silver nanoparticles stabilized by the
      polymer was significantly increased due to the complex effect between the crown
      ether embedded in the polymer and the silver nanoparticles.

PMID- 15491215
TI  - Self-generation of tiered surfactant superstructures for one-pot synthesis of
      Co3O4 nanocubes and their close- and non-close-packed organizations.
AB  - Self-generation of ionic organic capping from nonionic surfactant polyoxyethylene
      (20) sorbitan trioleate (Tween-85) has been realized for the controlled synthesis
      of single crystalline Co(3)O(4) quantum dots (3.0-5.7 nm) in cubic morphology
      from related layered hydroxide precursors at 80-95 degrees C. With chemical
      modification of hydrophobic functional groups on the surface of Co(3)O(4)
      nanocubes; furthermore, various nanocube-containing micellar superstructures can
      be further assembled through hydrophobic interactions between Tween-85 molecules
      and the surface coating under "one-pot" conditions. In particular, square
      arrangements, spherical domains, and line-assemblies of the prepared Co(3)O(4)
      nanocubes and their inter-transformations have been attained for the first time
      by manipulating intersurfactant-interactions. Hydrolysis of Tween-85 and the
      resultant tiered surfactant superstructures have been investigated with FTIR/UV
      vis/EA/TGA/DTA/XPS methods, and the capping species has been identified to be
      alkylated oleic carboxylate anions derived from Tween-85. Pronounced quantum
      confinement effects have been observed with the prepared Co(3)O(4) nanocubes, and
      the optical band gap energies determined are 3.95 and 2.13 eV, respectively, for
      O(2-)--> Co(2+) and O(2-)--> Co(3+) charge-transfer processes.

PMID- 15491216
TI  - Novel solid-state polymer electrolyte consisting of a porous layer-by-layer
      polyelectrolyte thin film and oligoethylene glycol.
AB  - A novel solid-state polymer electrolyte was constructed using layer-by-layer
      (LbL) polyelectrolyte assembly of linear poly(ethylenimine) (LPEI) and
      poly(acrylic acid) (PAA), combined with a plasticization step using oligoethylene
      glycol dicarboxylic acid (OEGDA). This composite film exhibits a relatively high
      ionic conductivity of 9.5 x 10(-5) S/cm at 25 degrees C and 22% relative
      humidity. Detailed characterization of the composite was undertaken using grazing
      angle Fourier transform infrared (GA-FTIR), atomic force microscopy (AFM),
      scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and
      impedance spectroscopy. After immersing the LPEI/PAA films into OEGDA aqueous
      solutions, the films exhibited a swelling behavior and increased surface
      roughness indicative of porosity induced by reorganization of ionic interactions
      between LPEI and PAA in acidic solution. This internal porous structure allows
      inclusion of OEGDA within the multilayer and increased ionic conductivity under
      ambient conditions due to the combined effects of plasticization of the LbL
      matrix by atmospheric water as well as the added mobility of ions in molten OEGDA
      within the composite.

PMID- 15491217
TI  - Preparation of nanostructured materials by heterocoagulation-interaction of
      montmorillonite with synthetic hematite particles.
AB  - A nanostructured, porous material was prepared by heterocoagulation of negatively
      charged montmorillonite with positively charged synthetic spherical hematite
      particles. The process of heterocoagulation of such particles was monitored by
      turbidimetric titrations over the pH range 2.5-7.5. On the basis of the results
      of turbidimetric measurements, a series of solid materials were prepared for
      further characterization using ESEM, BET, XRD, and FTIR techniques. Environmental
      scanning electron microscopy detected isolated hematite particles or small
      hematite aggregates on montmorillonite surfaces (mass ratios 8:1 and 4:1). At a
      mass ratio of 1:1, exfoliated montmorillonite layers, covering the hematite
      particles as semi-transparent blankets were seen. A low mass ratio led to compact
      hematite particle aggregates covering the montmorillonite surfaces. Nitrogen-gas
      adsorption isotherms revealed the sorption properties to be gradually dependent
      upon mass ratios. Pore volume distributions showed that mesopores with diameter
      of about 10-20 nm were produced in the heterocoagulates with mass ratios of 4:1,
      1:1, and 1:8. The sample prepared with a 4:1 mass ratio showed the greatest BET
      surface area, which decreased slightly upon sample calcination at 500 degrees C.
      X-ray diffraction measurements were used to investigate layer stacking, by
      comparing the integral intensities of d(001) reflection. For this purpose,
      samples with 4:1 mass ratios, prepared both by heterocoagulation and mechanical
      grinding, were used. It was found that heterocoagulation effectively diminished
      the stacking of the layers to about 85%; hence, a significant amount of
      fundamental, 1 nm thick montmorillonite layers was achieved in this sample.

PMID- 15491218
TI  - Incorporation of functionalized single-wall carbon nanotubes in dye-sensitized
      TiO2 solar cells.
AB  - Effects of incorporation of acid-treated single-wall carbon nanotubes (a-SWCNs)
      in TiO(2) film and of anchorage of dye-linked, a-SWCNs (hereafter dye-SWCNs) to
      the TiO(2)/electrolyte interface on photocurrent-voltage characteristics of dye
      sensitized solar cells were studied. Compared with an unmodified cell, the
      modified cell with the a-SWCNs in TiO(2) film showed a 25% increase in short
      circuit photocurrent (J(sc)). The J(sc) increase is correlated with improved
      connectivity between the a-SWCNs and the TiO(2) particles and with enhanced light
      scattering by TiO(2) clusters formed in the presence of the a-SWCNs. In the case
      of anchoring dye-SWCNs to the TiO(2)/electrolyte interface, the open-circuit
      voltage (V(oc)) increased by as much as 0.1 V, possibly due to the basicity of
      the TiO(2) surface from NH groups of ethylenediamine moieties of the anchored dye
      SWCNs.

PMID- 15491219
TI  - Characterization of self-assembled lamellar thermoresponsive silica-hydrogel
      nanocomposite films.
AB  - Mesostructured lamellar nanocomposite films with alternating silica and organic
      layers containing poly(N-isopropropyl acrylamide) (PNIPAM) were prepared using
      evaporation-induced self-assembly. A suitable theoretical approach to analyze the
      small-angle X-ray scattering (SAXS) patterns of oriented lamellar two-phase
      systems was applied to the SAXS data of films of varying composition, providing
      details on the self-assembly process, the composition, and the polymerization. In
      particular, this approach allowed an accurate determination of the thickness of
      the silica and the organic layer. The applicability of the SAXS approach was
      carefully tested with simulated data and verified by thermogravimetric analysis
      (TGA). TGA and (13)C NMR were used to study the polymerization and linkage to the
      silica matrix. SAXS and time-resolved grazing incidence SAXS revealed that the
      phase transition of PNIPAM at ca. 32 degrees C leads to a reversible
      expansion/contraction perpendicular to the layers on a time scale of ca. 30 min.

PMID- 15491220
TI  - Ta3N5 nanoparticles with enhanced photocatalytic efficiency under visible light
      irradiation.
AB  - Nanocrystalline Ta(3)N(5) particles with a surface area of more than 33 m(2)/g
      were synthesized by nitridation of nanosized Ta(2)O(5) particles using NH(3) as
      the reactant gas. It was found that nanocrystalline Ta(2)O(5) was converted into
      Ta(3)N(5) completely (by X-ray diffraction, XRD) at 700 degrees C within 5.0 h,
      which was much lower than the temperature 900 degrees C for the complete
      nitridation of micrometer-sized Ta(2)O(5) powder. The oxide precursor and the
      resulting nitride were characterized by XRD analysis, transmission electron
      microscopy, UV-vis diffuse reflectance spectra, and BET surface area techniques.
      The nitrogen contents in the prepared Ta(3)N(5) powders were quantitatively
      determined with a CHN elemental analyzer. Nanocrystalline Ta(3)N(5) showed an
      absorption edge of around 600 nm, and Ta(3)N(5) in the size of about 26 nm
      exhibited a blue shift of 15 nm in the adsorption edge. The photocatalytic
      activity of the prepared Ta(3)N(5) under UV-vis and visible light irradiation was
      compared to that of nanocrystalline TiO(2-x)N(x) using the photocatalytic
      degradation of methylene blue (MB) as a model reaction. The Ta(3)N(5)
      nanoparticles showed the significantly enhanced photocatalytic activity for the
      degradation of MB in comparison with the larger-sized Ta(3)N(5). Moreover, the
      nanocrystalline Ta(3)N(5) showed much higher photocatalytic activity under
      visible light irradiation compared with TiO(2-x)N(x) in the same size.

PMID- 15491221
TI  - Solid-state NMR study of intercalated species in poly(epsilon-caprolactone)/clay
      nanocomposites.
AB  - The structure and dynamics of surfactant and polymer chains in intercalated
      poly(epsilon-caprolactone)/clay nanocomposites are characterized by (31)P magic
      angle spinning (MAS) and (13)C cross-polarization MAS NMR techniques. To obtain
      hybrid materials with the low polymer content required for this study, in situ
      intercalative polymerization was performed by adapting a published procedure.
      After nanocomposite formation, the chain motion of the surfactant is enhanced in
      the saponite-based materials but reduced in the Laponite ones. Compared to the
      starting clay, the trans conformer population of the surfactant hydrocarbon chain
      in the nanocomposite decreases for the saponite systems. Mobility of the polymer
      chain is higher in the nanocomposites than in the bulk phase. The charge of the
      modified saponite does not significantly influence chain mobility in the
      nanocomposites.

PMID- 15491222
TI  - Synthesis of NiGa layered double hydroxides. A combined EXAFS, SAXS, and TEM
      study. 2. Hydrolysis of a Ni2+/Ga3+ solution.
AB  - Takovites are nickel-based layered double hydroxides (LDH) with a general formula
      that can be written as Ni(1-x)Al(x)(OH)2, A(z-)(x/z), yH(2)O, where A is a
      compensating interlayer anion. As in some other LDH samples, the positive charge
      of the layer can be adjusted upon synthesis and various anions can be exchanged
      in the interlayer region. It is then important to understand the synthesis
      pathway of these materials. We then undertook a study on the hydrolytic behavior
      of pure Ni salts and mixtures of Ni and Ga salts. This paper focuses on the
      hydrolysis of Ni(2+) and Ga(3+) ions, together in solution, carried out by base
      addition. The samples will be defined by their hydrolysis ratio R = [OH(
      )]/([Ni(2+)] + [Ga(3+)]). Small-angle X-ray scattering (SAXS) and transmission
      electron microscopy (TEM) were used to obtain information on the colloidal
      species size and shape on a large scale. Each hydrolyzed sample was also studied
      by Ni K-edge and Ga K-edge extended X-ray absorption fine structure (EXAFS) to
      obtain information on the local structure of the species in suspension. SAXS
      curves reveal the presence of bidimensional objects whatever the R values. The
      platelets formed for R values >/=1.1 are slightly thicker and smaller in size,
      which may be linked to their different natures. Complementary information is
      provided by TEM analysis: the first colloids formed have a structure very close
      to that of alpha-GaOOH, as shown by electronic diffraction. Those structures are
      progressively replaced by Ni-Ga LDH platelets with increasing hydrolysis ratio,
      which are the only species in suspension for R = 2.0, as shown by XRD. EXAFS
      results confirm the complete hydrolysis of gallium before the formation of Ni-Ga
      LDH phases.

PMID- 15491223
TI  - Selective Ni-P electroless plating on photopatterned cationic adsorption films
      influenced by alkyl chain lengths of polyelectrolyte adsorbates and additive
      surfactants.
AB  - We demonstrated that the photopatterned single-layer adsorption film of poly(1
      dodecyl-4-pyridinium bromide) on a silica surface was available for a template of
      nickel-phosphorus (Ni-P) electroless plating through sensitization with a SnCl(2)
      aqueous solution and activation with a PdCl(2) aqueous solution. Four kinds of
      poly(1-alkyl-4-vinylpyridinium halide)s bearing methyl, propyl, hexyl, and
      dodecyl groups were prepared. The cationic polymers were adsorbed by a negatively
      charged silica surface from their solutions, to form single-layer adsorption
      films exhibiting desorption-resistance toward deionized water and ethanol. The
      organic adsorption films could be decomposed completely by exposure to 172 nm
      deep-UV light. The formation and decomposition of the single-layer films were
      confirmed by deep-UV absorption spectral measurement and zeta-potential
      measurement. Ni-P electroless plating was carried out on the photopatterned
      adsorption films, using three types of SnO(x) colloidal materials without and
      with cationic or anionic surfactant as catalyst precursors in the sensitization
      step. In the case of the negatively charged SnO(x) colloids surrounded by anionic
      surfactant, Ni-deposition took place preferentially on the cationic adsorption
      films remaining in unexposed regions. The Ni-deposition was accelerated
      significantly on the cationic adsorption film bearing dodecyl groups. It was
      obvious by ICP-AES analyses that the hydrophobic long-chain dodecyl groups in the
      adsorption film could promote the adsorption of the negative SnO(x) colloids on
      the film surface, followed by much nucleus formation of zerovalent Pd catalysts
      useful for the electroless plating. The result of our experiment clearly showed
      that, in addition to electrostatic interaction, van der Waals interaction
      generating between the hydrophobic long-chain hydrocarbons of the adsorption film
      and the surfactant improved significantly the adsorption stability of the SnO(x)
      colloids, resulting in highly selective Ni-deposition in accord with the
      photopattern shape of the cationic single-layer adsorption film.

PMID- 15491224
TI  - Single-walled carbon nanotubes embedded in oriented polymeric nanofibers by
      electrospinning.
AB  - The electrospinning process was used successfully to embed single-walled carbon
      nanotubes (SWCNTs) in a poly(ethylene oxide) (PEO) matrix, forming composite
      nanofibers. Initial dispersion of SWCNTs in water was achieved by the use of an
      amphiphilic alternating copolymer of styrene and sodium maleate. The resulting
      dispersions were stable, having a dark, smooth, ink-like appearance. For
      electrospinning, the dispersions were mixed with PEO solution in an ethanol/water
      mixture. The distribution and conformation of the nanotubes in the nanofibers
      were studied by transmission electron microscopy (TEM). Oxygen plasma etching was
      used to expose the nanotubes within the nanofibers to facilitate direct
      observation. Nanotube alignment within the nanofibers was shown to depend
      strongly on the quality of the initial dispersions. Well-dispersed and separated
      nanotubes were embedded in a straight and aligned form, while entangled
      nonseparated nanotubes were incorporated as dense aggregates. X-ray diffraction
      demonstrated a high degree of orientation of the PEO crystals in the electrospun
      nanofibers with embedded SWCNTs. This result is in pronounced distinction to the
      detrimental effect of incorporation of multiwalled carbon nanotubes on polymer
      orientation in electrospun nanofibers, as reported previously.

PMID- 15491225
TI  - Structure of the mesoporous silica SBA-2, determined by a percolation analysis of
      adsorption.
AB  - We have carried out a percolation analysis of the adsorption of ethane and
      nitrogen in SBA-2, a structured mesoporous silica consisting of a hexagonal close
      packed (hcp) array of spherical cavities connected by cylindrical channels. Our
      analysis explains the different uptakes of nitrogen and ethane in terms of the
      greater accessibility of the network to the smaller nitrogen molecule. The
      analysis also allows us to quantify the connectivity of the SBA-2 pore network.
      The effective coordination number of the cavities, defined as the average number
      of channels per cavity that are large enough to allow nitrogen to pass, is 4.9,
      much less than the theoretical maximum value of 12. Taking into account only the
      smaller set of channels large enough to admit ethane, the effective coordination
      number is 1.8, just above the percolation threshold of the network.

PMID- 15491226
TI  - Colloidal aggregation induced by long range attractions.
AB  - The structure of colloidal clusters formed by long-range attractive interactions
      under diluted conditions is studied by means of Monte Carlo simulations. For a
      not-too-long attraction range, clusters show self-similar internal structure with
      lower density than that typical for diffusive aggregation. For long-range
      interactions, low kappa, nonfractal clusters are formed (dense at short scales
      but open at long ones). The dependence on the volume fraction shows that more
      compact clusters are grown the higher the colloidal density for diffusive
      aggregation and attraction-driven aggregation in the fractal regime. The whole
      trend is explained in terms of the interpenetration among aggregates. In
      attraction-driven aggregations, the interpenetration of clusters competes with
      aggregation in the tips of the clusters, causing low-density clusters.

PMID- 15491227
TI  - CFD simulation and analysis of emulsion droplet formation from straight-through
      microchannels.
AB  - We recently proposed a technique for preparing monodisperse emulsions with a
      coefficient of variation below 5% from a silicon array of micrometer-sized
      channels perpendicular to the plate surface, named a straight-through
      microchannel (MC). This study involved three-dimensional computational fluid
      dynamics (CFD) simulations to calculate the formation of an oil-in-water (O/W)
      emulsion droplet from straight-through MCs with circular and elliptic cross
      sections. The CFD results demonstrated that the oil phase that passed through the
      elliptic MCs exceeding a threshold aspect ratio between 3 and 3.5 was cut off
      spontaneously into a small droplet with a diameter of approximately 40 microm.
      Sufficient space for water at the channel exit had to be maintained for
      successful droplet formation. The formation and shrinkage of a neck inside the
      channel caused an increased pressure difference inside the channel and an
      increased velocity value near the neck. The pressure and velocity values at the
      neck drastically changed, and the neck was cut off instantaneously just before
      the completion of droplet formation. This process was triggered by a gradually
      increased pressure difference between the circular neck and inflating oil phase.
      The findings obtained in this paper provide useful numerical and visual
      information about the droplet formation phenomena from the straight-through MCs.
      The CFD results were verified by the experimental results, showing that the CFD
      approach can help design a suitable channel structure.

PMID- 15491228
TI  - Coupled hydrophilic and charge-transfer interactions between polychlorinated
      methanes, ethanes, and ethenes and redox-manipulated smectite clay minerals.

PMID- 15491229
TI  - Solvent-induced large compound vesicle of [60]fullerene containing poly(tert
      butyl methacrylate).

PMID- 15491230
TI  - Drug combinations for bipolar spectrum disorders: evidence-based prescribing or
      prescribing-based evidence?

PMID- 15491232
TI  - A clinical perspective of attention-deficit/hyperactivity disorder into
      adulthood.
AB  - OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is a common
      psychiatric disorder that affects all age groups. Recent data on the clinical
      presentation, comorbidity, neurobiology, and treatment are reviewed. METHOD:
      Using the search term ADHD, a selective PubMed review of the clinical literature
      was undertaken to evaluate recent data relevant to ADHD with attention to a life
      span perspective of the disorder. RESULTS: A growing literature indicates that
      ADHD is more persistent than previously thought and has a developmental
      variability in its presentation. The disorder impairs academic, social, and
      occupational functioning and is often associated with comorbidity, including
      cigarette smoking and substance abuse. Considerable evidence suggests that the
      disorder has a strong genetic component and a biological underpinning; the
      pathophysiology includes dysfunction in both noradrenergic and dopaminergic
      systems. Both psychosocial therapy and pharmacotherapy have been shown effective
      in the treatment of the disorder throughout the life span. The therapeutic
      effectiveness of pharmacologic agents in the treatment of ADHD has been
      attributed to noradrenergic and/or dopaminergic effects. CONCLUSION: ADHD is
      associated with impairment and comorbidity throughout the life span. Growing
      evidence suggests the importance of short- and long-term management of the
      disorder. While the long-term treatment of ADHD is expected to lessen the
      individual's impairment, the outcome for adults who have received treatment since
      childhood requires further study.

PMID- 15491233
TI  - Risk factors for premenstrual dysphoric disorder in a community sample of young
      women: the role of traumatic events and posttraumatic stress disorder.
AB  - BACKGROUND: There is some evidence that the onset and course of premenstrual
      syndrome is related to stress; however, few studies have explored the role of
      traumatic events and post-traumatic stress disorder (PTSD) as risk factors for
      the development of premenstrual dysphoric disorder (PMDD). METHOD: A community
      cohort of 1488 women (aged 14-24 years at baseline) were prospectively and
      longitudinally evaluated up to 3 times over a period of about 42 months from 1995
      to 1999. The DSM-IV version of the Munich-Composite International Diagnostic
      Interview was used to establish PMDD and PTSD diagnostic status; stressful life
      events and conditions were assessed with the Munich Events List and the Daily
      Hassles Scale. Prevalence and incidence of either threshold or subthreshold PMDD
      from baseline to the second follow-up were calculated. Risk factors, including
      prior comorbid mental disorders and traumatic events, were examined using
      logistic regression analysis. RESULTS: The incidence of threshold PMDD was 3.0%.
      The most powerful predictors were subthreshold PMDD at baseline (OR = 11.0, 95%
      CI = 4.7 to 25.9). Traumatic events greatly increased the odds of developing PMDD
      at follow-up (OR = 4.2, 95% CI = 1.2 to 12.0). Other predictors were a history of
      anxiety disorder (OR = 2.5, 95% CI = 1.1 to 5.5) and elevated daily hassles
      scores (OR = 1.6, 95% CI = 1.1 to 2.3). Both were also associated with the risk
      of developing subthreshold PMDD, although the association was less robust.
      CONCLUSIONS: Traumatic events and pre-existing anxiety disorders are risk factors
      for the development of PMDD. The underlying mechanisms are unknown, making
      further investigation necessary.

PMID- 15491234
TI  - A 3-month, follow-up, randomized, placebo-controlled study of repetitive
      transcranial magnetic stimulation in depression.
AB  - BACKGROUND/OBJECTIVE: There is evidence for an antidepressant effect of
      repetitive transcranial magnetic stimulation (rTMS), but little is known about
      posttreatment course. Therefore, we conducted a placebo-controlled, double-blind
      study in depressed patients in order to investigate the effect of rTMS on
      depression over 12 weeks after completion of the 2-week stimulation period.
      METHOD: 55 patients with a moderate or severe DSM-IV major depressive episode
      were randomly assigned to rTMS or sham treatment. rTMS was given daily for 10
      days over the left dorsolateral prefrontal cortex with the following treatment
      parameters: 20 Hz, 20 trains of 2 seconds, 30 seconds between trains, and 80%
      motor threshold. The effect of rTMS on depression was rated repeatedly with the
      17-item Hamilton Rating Scale for Depression (HAM-D) during the 2-week period of
      stimulation and the 12-week follow-up period conducted from 1997 to 2001.
      RESULTS: We found a modest, clinically nonrelevant decrease in HAM-D scores in
      both rTMS and sham patients over 2 weeks of treatment. However, over the
      subsequent 12-week follow-up, the rTMS group continued to improve significantly
      compared with the placebo group. CONCLUSION: Decrease of depressive symptoms may
      continue after the cessation of rTMS stimulation.

PMID- 15491235
TI  - Behavioral and psychological symptoms in patients with dementia as a target for
      pharmacotherapy with risperidone.
AB  - OBJECTIVE: To examine the effect of risperidone on specific behavioral and
      psychological symptoms of dementia (BPSD). METHOD: We conducted a post hoc
      exploratory analysis of an integrated database from 3 randomized, controlled
      trials of risperidone versus placebo in treating 1150 nursing home residents with
      BPSD. Changes in scores were measured for items on the Cohen-Mansfield Agitation
      Inventory (CMAI) and Behavioral Pathology in Alzheimer's Disease Rating Scale
      (BEHAVE-AD). RESULTS: On the CMAI, risperidone was significantly more effective
      in treating hitting (p = .000), hurt self or other (p = .005), cursing or verbal
      aggression (p = .000), repetitive sentences or questions (p = .001), scratching
      (p = .041), general restlessness (p = .001), grabbing onto people (p = .028),
      constant request for attention (p = .041), pacing and aimless wandering (p =
      .013), and performing repetitious mannerisms (p = .045). On the BEHAVE-AD,
      risperidone was significantly more effective in treating physical threats and/or
      violence (p = .000), verbal outbursts (p = .000), other anxieties (p = .01),
      agitation (p = .000), tearfulness (p = .03), and nonparanoid delusions (p = .02).
      CONCLUSIONS: The items from the BEHAVE-AD and CMAI that were improved with
      risperidone included psychotic, agitated, and aggressive symptoms. These data
      suggest that risperidone is more effective than placebo in treating a variety of
      symptoms associated with dementia.

PMID- 15491236
TI  - Insulin resistance and increased leptin concentrations in noncompliant
      schizophrenia patients but not in antipsychotic-naive first-episode schizophrenia
      patients.
AB  - BACKGROUND: The onset of diabetes and impaired glucose metabolism among
      schizophrenic patients has been the topic of numerous recently published
      articles, with research implicating weight gain, the use of antipsychotic
      medication, history of diabetes mellitus in family members, and the diagnosis of
      schizophrenia itself as risk factors. Therefore, it was the aim of this study to
      determine the glucose metabolism parameters in noncompliant unmedicated
      schizophrenic patients (antipsychotic-free) and first-episode antipsychotic-naive
      schizophrenic patients to investigate whether there is a preexisting impairment
      of glucose metabolism in never-medicated schizophrenic patients. METHOD: Plasma
      glucose, insulin, C-peptide, and leptin concentrations were determined in 50
      antipsychotic-free and 50 antipsychotic-naive DSM-IV schizophrenia patients and
      50 healthy control subjects. Insulin resistance was calculated through the
      homeostatic model assessment (HOMA). The General Linear Model (univariate)
      procedure was used to perform analysis of covariance. Patients were recruited
      from July 2001 to December 2002. RESULTS: Antipsychotic-free patients showed
      significantly increased insulin (p = .001) and C-peptide (p = .02) concentrations
      and a significantly higher degree of insulin resistance (p = .003), as measured
      with the HOMA index, in comparison with the antipsychotic-naive patients and the
      control group. Significantly increased leptin concentrations (p = .000) were also
      noted in the antipsychotic-free patients and were attributed to the effects of
      body mass index (p = .000) and sex (p = .000). CONCLUSIONS: The results reported
      in this study suggest the effect of previous antipsychotic treatment on glucose
      metabolism parameters and weight-related hormones such as leptin, while ruling
      out a preexisting impairment of glucose metabolism in never-medicated first
      episode schizophrenic patients.

PMID- 15491237
TI  - Computer-assisted self-assessment in persons with severe mental illness.
AB  - BACKGROUND: It has been difficult to improve care for severe mental illness (SMI)
      in usual care settings because clinical information is not reliably and
      efficiently managed. Methods are needed for efficiently collecting this
      information to evaluate and improve health care quality. Audio computer-assisted
      self-interviewing (ACASI) can facilitate this data collection and has improved
      outcomes for a number of disorders, suggesting the need to test its accuracy and
      reliability in people with SMI. METHOD: Ninety patients with DSM-IV schizophrenia
      or schizoaffective disorder (N = 45) or bipolar disorder (N = 45) recruited
      between Oct. 15, 2002, and July 1, 2003, were randomly assigned to 1 of 2 study
      groups and completed 2 standardized symptom surveys (Revised Behavior and Symptom
      Identification Scale and the symptom severity scale of the Schizophrenia Outcomes
      Module 2) 20 minutes apart in a crossover study design. Half of the patients
      first completed the scales via an in-person interview, and the other half first
      completed the scales via an ACASI survey self-administered through an Internet
      browser using a touchscreen developed to meet the cognitive needs of people with
      SMI. We evaluated attitudes toward ACASI, understanding of the ACASI survey,
      internal consistency, correlations between the ACASI and interview modes,
      concurrent validity, and a possible administration mode bias. RESULTS: All ACASI
      and in-person interview scales had similar internal reliability, high
      correlations (r = 0.78-1.00), and mean scores similar enough as not to be
      different at p < .05. A large majority rated the ACASI survey as easier, more
      enjoyable, more preferable if monthly completion of a survey were required, and
      more private, and 97% to 99% perfectly answered questions about how to use it.
      CONCLUSION: ACASI data collection is reliable among people with bipolar disorder
      and schizophrenia and could be a valuable tool to improve their care.

PMID- 15491238
TI  - The effect of clozapine on factors controlling glucose homeostasis.
AB  - BACKGROUND: This prospective study examines the effect of clozapine on factors
      determining glucose homeostasis. METHOD: The sample consisted of all patients
      meeting DSM-IV criteria for schizophrenia who commenced clozapine treatment
      within the South London and Maudsley hospitals during 1 year (2000-2001). Growth
      hormone (GH), insulin-like growth factor-1 (IGF-1), and IGF binding protein-1
      (IGFBP-1) were measured in 19 patients (10 female; mean age = 31.1 years [SD =
      5.8]; 9 black British/African, 10 white British) before and after a mean of 2.5
      (SD = 0.9) months of clozapine treatment. RESULTS: Baseline IGFBP-1 was low.
      IGFBP-1, GH, and IGF-1 were not significantly changed by clozapine treatment.
      CONCLUSIONS: Clozapine does not alter GH, IGF-1, or IGFBP-1 within 3 months of
      commencing treatment, indicating that alteration in glucose tolerance associated
      with clozapine treatment involves other mechanisms yet to be elucidated. Baseline
      abnormalities in IGFBP-1 indicate a preexisting susceptibility to glucoregulatory
      dysfunction.

PMID- 15491239
TI  - Effectiveness of low doses of paroxetine controlled release in the treatment of
      major depressive disorder.
AB  - CONTEXT: Paroxetine controlled release (CR) is approved for the treatment of
      major depressive disorder (MDD) in the dosage range of 25 to 62.5 mg daily.
      However, lower daily doses (12.5 mg and 25 mg) of this formulation have not been
      investigated in the treatment of MDD. If the 12.5-mg and 25-mg doses are found to
      be efficacious, these lower doses may well convey a superior tolerability profile
      for paroxetine CR in the treatment of MDD. OBJECTIVE: To evaluate the
      antidepressant efficacy and tolerability profile of daily doses of paroxetine CR
      12.5 mg and 25 mg versus placebo in the treatment of MDD. DESIGN AND SETTING:
      Randomized, double-blind, placebo-controlled clinical trial conducted in 40
      clinical investigation centers in the United States. PARTICIPANTS: 447 adult (>
      or = 18 years of age) outpatients who met DSM-IV criteria for MDD and with a
      baseline 17-item Hamilton Rating Scale for Depression (HAM-D) score of at least
      20 comprised the intent-to-treat study population (mean age = 38.8 years; 58.4%
      female; 75.6% white). INTERVENTION: Eligible patients completing a 1-week single
      blind placebo run-in period were randomly assigned to receive once-a-day study
      medication (paroxetine CR 12.5 mg [N = 156], paroxetine CR 25 mg [N = 154], or
      placebo [N = 149]) in an 8-week, double-blind, parallel cell comparison. MAIN
      OUTCOME MEASURES: The primary efficacy measure was the change from baseline to
      study endpoint (week 8) as measured by the HAM-D. Secondary efficacy measures
      included change from baseline to study endpoint as assessed by both the depressed
      mood item on the HAM-D and the Clinical Global Impressions (CGI) Severity of
      Illness scale (CGI-S). The proportion of patients considered at study endpoint to
      be in response (CGI-Improvement score of 1 or 2) or in remission (HAM-D < or = 7)
      in the 3 treatment groups was also compared. Quality of life was assessed by the
      change from baseline in total score of the short form of the Quality of Life
      Enjoyment and Satisfaction Questionnaire (Q-LES-Q). Safety observations were made
      by assessing the proportion of patients who had adverse experiences, including
      laboratory and electrocardiographic abnormalities, during the treatment period.
      RESULTS: The primary efficacy analysis revealed that both the 12.5-mg and the 25
      mg paroxetine CR treatment groups were associated with significant therapeutic
      effects (change in HAM-D score) from baseline to study endpoint (LOCF: p = .038,
      95% CI = -3.38 to -0.09 and p = .005, 95% CI = -4.06 to -0.74, respectively).
      Results from the Wilcoxon rank sum test of the depressed mood item of the HAM-D
      (p = .011, 95% CI = -0.57 to -0.07) demonstrated significant efficacy in the 25
      mg treatment group but not in the 12.5-mg group. However, LOCF analysis of the
      CGI-S revealed significant therapeutic effects for both the 12.5-mg (p = .018,
      95% CI = -0.61 to -0.06) and 25-mg (p < .001, 95% CI = -0.78 to -0.22) treatment
      groups. Significantly more patients in the 25-mg paroxetine CR-treated group than
      in the placebo-treated group met criteria for response (CGI-Improvement score of
      1 or 2, p = .035, OR = 1.68, 95% CI = 1.04 to 2.73) as well as for remission (HAM
      D score </= 7, p = .013, OR = 1.96, 95% CI = 1.15 to 3.33). Neither HAM-D
      remission analysis nor CGI responder analysis showed statistical separation from
      placebo for paroxetine CR 12.5-mg treatment. Quality of life improvements were
      statistically significant for the 25-mg treatment (p = .041, 95% CI = 0.17 to
      8.03) on the Q-LES-Q total score. Post hoc LOCF analyses of HAM-D sleep
      disturbance, psychic anxiety, and anxiety/somatization factors revealed
      significant improvements from baseline in the paroxetine CR 25-mg and 12.5-mg
      treatment groups. The types of adverse events reported in the 12.5-mg and 25-mg
      groups were similar to those reported with paroxetine CR at the customary 25-mg
      to 62.5-mg range; however, the lower doses of paroxetine CR were associated with
      a relatively reduced incident rate of these adverse events and an overall
      improved tolerability compared with the incident rate and tolerability profile
      associated with the customary dose range of paroxetine CR (25 to 62.5 mg).
      CONCLUSION: Paroxetine CR, at 12.5 mg/day and 25 mg/day, demonstrated significant
      antidepressant effects.

PMID- 15491240
TI  - Weight gain during long-term treatment of obsessive-compulsive disorder: a
      prospective comparison between serotonin reuptake inhibitors.
AB  - BACKGROUND: The effect of extended anti-depressant treatment on weight has been
      poorly investigated. Also unknown is whether different compounds have
      differential effects. The aim of the present study was to assess changes in
      weight in obsessive-compulsive disorder (OCD) patients treated for 2.5 years with
      clomipramine or selective serotonin reuptake inhibitors. METHOD: 138 DSM-IV OCD
      patients who responded to 6-month acute treatment at the Mood and Anxiety
      Disorders Unit, Department of Neuroscience, University of Turin, Italy, were
      followed-up for 2 years while receiving open-label clomipramine, citalopram,
      fluoxetine, fluvoxamine, paroxetine, or sertraline. Patients were consecutively
      recruited and followed from May 1998 to March 2003. The mean percentage change in
      weight was compared for each group, as was the proportion of patients who had a >
      or = 7% weight increase from baseline. RESULTS: At the end of the 2.5-year study
      period, patients had gained a mean of 2.5% of their body weight with respect to
      baseline (1.58 kg); 14.5% of the total sample experienced a significant (> or =
      7%) weight increase. Within each but the fluoxetine treatment group, paired t
      tests showed a significant increase in weight from baseline to final visit.
      Analysis of variance showed a significant difference between treatment groups (p
      = .009), with clomipramine being associated with the highest weight increase and
      fluoxetine and sertraline with the lowest. A higher proportion of clomipramine
      treated patients (34.8%) gained > or = 7% in weight as compared with sertraline
      and fluoxetine, which accounted for the lowest percentage of patients with a
      significant weight gain (4.5% and 8.7%, respectively), although this difference
      was not statistically significant. CONCLUSION: Risk of weight gain during
      extended serotonin reuptake inhibitor treatment for OCD differs depending on
      which compound is used. The differences among antiobsessive drugs may affect
      compliance with medication and health risks.

PMID- 15491241
TI  - Attitudes of schizophrenia outpatients toward psychiatric medications:
      relationship to clinical variables and insight.
AB  - BACKGROUND: Attitude toward medications is important for medication adherence. A
      patient's drug attitude probably reflects a weighing of benefits against
      experienced or anticipated side effects or risks associated with the medication.
      We predicted (1) that drug attitudes would be more positive among schizophrenia
      patients taking second-generation compared to first-generation antipsychotics
      because of their greater tolerability and efficacy; and (2) that greater insight
      into illness, fewer extrapyramidal symptoms, and better social functioning would
      be associated with better attitudes toward psychiatric medication. METHOD: In a
      cross-sectional study of 81 DSM-IV-diagnosed schizophrenia outpatients, we used
      multivariate analysis to determine clinical and demographic predictors of drug
      attitude. Drug attitude was assessed with the 10-item Drug Attitude Inventory
      (DAI). The relationship between the DAI and psychopathology, insight,
      extrapyramidal symptoms, level of functioning, and type of antipsychotic (first
      generation versus second-generation versus clozapine) was examined. RESULTS: Less
      awareness of current symptoms, presence of deficit symptoms, and employment
      predicted a negative attitude toward psychiatric medications. Extrapyramidal
      symptoms did not predict drug attitude. Drug attitudes were no different between
      patients taking first- or second-generation antipsychotics or clozapine.
      CONCLUSION: Patients may not favor second-generation over first-generation
      antipsychotics, and extrapyramidal symptoms may not be a primary factor
      determining attitudes. While attitudes may be more positive in patients who
      recognize therapeutic drug effects, patients who work may view medications
      particularly negatively, possibly due to a sense of stigma. Because drug
      attitudes may reflect compliance and are difficult to predict, clinicians should
      inquire directly.

PMID- 15491242
TI  - Prevalence, trends, and factors associated with antipsychotic polypharmacy among
      Medicaid-eligible schizophrenia patients, 1998-2000.
AB  - OBJECTIVE: To determine the prevalence, trends, and factors associated with
      antipsychotic polypharmacy categorized according to type of antipsychotic and
      duration of use and to contrast usage patterns with published treatment
      guidelines. METHOD: A retrospective cohort study was designed, and Medicaid
      recipients > or = 16 years of age with a schizophrenia diagnosis (ICD-9-CM =
      295.xx) between 1998 and 2000 were identified from the California (20% random
      sample) and Georgia Medicaid claims databases. Use of anti-psychotic polypharmacy
      was categorized based on duration (long-term polypharmacy was defined as lasting
      > 2 months), and long-term use was further categorized based on type of
      antipsychotic combinations (clozapine, conventional, and atypical). The
      prevalence, mean duration, and frequency of and yearwise trends in antipsychotic
      polypharmacy were estimated. A stepwise logistic variable selection procedure was
      used to identify factors associated with long-term antipsychotic polypharmacy.
      RESULTS: Of a total of 31,435 persons with schizophrenia, the 1998-2000
      prevalence of anti-psychotic polypharmacy was 40% (N = 12,549; mean age = 43
      years; white, 47%; female, 48%; mean duration of polypharmacy = 149 days), and
      long-term antipsychotic polypharmacy prevalence was 23% (N = 7222, mean duration
      = 236 days). The prevalence of atypical antipsychotic poly-pharmacy increased
      between 1998 and 2000 (p < .0001). Use of newer atypicals such as quetiapine (OR
      = 18.32) and older conventionals such as chlorpromazine (OR = 28.87) was strongly
      associated with long-term antipsychotic polypharmacy. CONCLUSION: Antipsychotic
      polypharmacy is widely prevalent, is prescribed for long durations, and is an
      increasing phenomenon among Medicaid-eligible schizophrenia patients, indicating
      a significant discrepancy with treatment guidelines (which do not advocate the
      use of any poly-pharmacy except for short-term periods when transitioning
      patients to new antipsychotics). Further research evaluating the effects of
      antipsychotic polypharmacy in schizophrenia patients may assist in defining the
      scope and potential of such use.

PMID- 15491243
TI  - Seasonality of birth in seasonal affective disorder.
AB  - BACKGROUND: Season of birth or seasonal changes in putative etiologic factors are
      thought to influence the development of several psychiatric illnesses. The aim of
      this investigation was to examine seasonal differences in the frequency of birth
      in a clinical sample of patients with seasonal affective disorder (SAD). METHOD:
      553 outpatients suffering from SAD-DSM-IV-defined depressive disorder with winter
      type seasonal pattern-who had been diagnosed and treated at the Department of
      General Psychiatry (University of Vienna, Austria) between 1994 and 2003, were
      included in this evaluation. We compared the observed number of births in our
      sample with expected values calculated from the general population. RESULTS:
      There was a significant deviation of the observed number of births from the
      expected values calculated on a monthly basis (p = .009). When comparing quarters
      (periods of 3 months), we found fewer births than expected in the first quarter
      of the year and a slight excess of births in the second and third quarters (p =
      .034). There were also more births in the spring/summer season and fewer than
      expected in fall and winter (p = .029). Interestingly, patients with melancholic
      depression were more frequently born in fall/winter and less often in
      spring/summer compared with patients with atypical depression (p = .008).
      CONCLUSION: Besides genetic factors, season of birth or seasonal changes in
      environmental factors also could influence the development of SAD. In addition,
      birth effects seem to be dependent on the symptom profile of the patients, but
      further studies are needed to elucidate the underlying mechanisms of these
      observations.

PMID- 15491244
TI  - Response acceleration with mirtazapine augmentation of citalopram in obsessive
      compulsive disorder patients without comorbid depression: a pilot study.
AB  - BACKGROUND: Therapeutic action of selective serotonin reuptake inhibitors (SSRIs)
      is delayed from 8 to 12 weeks in patients with obsessive-compulsive disorder
      (OCD). Several different agents have been tested to reduce the SSRI therapeutic
      latency time. Mirtazapine, an antagonist at alpha2-adrenoceptors, does not
      enhance serotonin (5-HT) neurotransmission directly but disinhibits the
      norepinephrine activation of 5-HT neurons and thereby increases 5-HT
      neurotransmission by a mechanism that may not require a time-dependent
      desensitization of receptors. The present study was undertaken to determine
      whether the mirtazapine-citalopram combination could induce an earlier and/or
      greater effect on the 5-HT system in OCD subjects than citalopram alone. METHOD:
      Forty-nine patients with OCD (DSM-IV) without comorbid depression were randomly
      assigned to a 2-tailed, single-blind, 12-week clinical trial with citalopram (20
      80 mg/day) plus placebo or citalopram plus mirtazapine (15-30 mg/day).
      Assessments were performed weekly with the Yale-Brown Obsessive Compulsive Scale
      (YBOCS), the Hamilton Rating Scale for Depression, and the Clinical Global
      Impressions scale. Data were collected from November 2001 to July 2003. RESULTS:
      The citalopram plus mirtazapine group achieved a reduction of at least 35% in
      YBOCS score and a "much improved" or "very much improved" rating on the Clinical
      Global Impressions-Improvement scale from the fourth week, while the citalopram
      plus placebo group obtained these results only from the eighth week. The number
      of responders was higher in the citalopram plus mirtazapine group at the fourth
      week of treatment, while no difference between groups in the response rate was
      noted at the eighth and twelfth weeks of treatment. CONCLUSIONS: We found an
      earlier onset of response action in OCD symptoms and reduced undesired side
      effects when mirtazapine was added to citalopram. This augmentation strategy
      deserves clinical and research consideration through further double-blind,
      placebo-controlled studies.

PMID- 15491245
TI  - On the threshold of disorder: a study of the impact of the DSM-IV clinical
      significance criterion on diagnosing depressive and anxiety disorders in clinical
      practice.
AB  - BACKGROUND: Two recent reanalyses of epidemiologic studies found that adding a
      clinical significance criterion reduced disorder prevalence. Patients presenting
      for clinical care are usually distressed or impaired by their symptoms; thus, the
      DSM-IV clinical significance criterion might have little impact on diagnosis in
      clinical practice. In the present report from the Rhode Island Methods to Improve
      Diagnostic Assessment and Services (MIDAS) project, we examine the impact of the
      DSM-IV clinical significance criterion on diagnostic frequencies of depressive
      and anxiety disorders in psychiatric outpatients. METHOD: 1500 psychiatric
      outpatients were evaluated with the Structured Clinical Interview for DSM-IV. We
      determined the percentage of patients who met symptom criteria but did not meet
      the DSM-IV clinical significance criterion for major depressive disorder,
      posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), social
      phobia, specific phobia, panic disorder, and obsessive-compulsive disorder.
      RESULTS: No patient who met the symptom criteria for current major depressive
      disorder or PTSD failed to meet the clinical significance criterion. Less than 2%
      of patients meeting the symptom criteria for current GAD did not meet the
      clinical significance criterion. There was variability among the remaining
      anxiety disorders in the percentage of symptomatic patients who met the clinical
      significance criterion. CONCLUSION: In psychiatric patients, the clinical
      significance criterion had little impact on diagnosing major depressive disorder,
      GAD, and PTSD, disorders that are defined, in part, by disruptions of daily
      regulatory domains such as sleep, appetite, energy, and concentration. In
      contrast, the clinical significance criterion had a greater impact in determining
      whether phobic fears, obsessive thoughts, and panic attacks were sufficiently
      distressing or impairing to qualify for disorder status.

PMID- 15491246
TI  - Combination treatment with nefazodone and cognitive-behavioral therapy for
      relapse prevention in alcohol-dependent men: a randomized controlled study.
AB  - BACKGROUND: This study evaluated the serotonergic antidepressant nefazodone
      versus placebo and specific cognitive-behavioral therapy (CBT) versus
      nondirective group counseling (GC) for relapse prevention in alcohol dependence
      in a large prospective, randomized, and placebo-controlled double-blind study at
      3 German university centers. METHOD: 242 male patients fulfilling at least 5
      criteria for alcohol dependence according to DSM-IV and ICD-10 were eligible,
      after detoxification, for one of the following treatment combinations: nefazodone
      + CBT, nefazodone + GC, placebo + CBT, and placebo + GC. Either nefazodone or
      placebo was administered throughout the evaluation period of 15 months. Either
      CBT or GC was applied during the first 12 weeks as group therapy according to
      operationalized manuals. The main outcome measures (assessed at 3 and 12 months
      of treatment) were the cumulative number of abstinent days, the amount of ethanol
      consumed during specified evaluation periods of 3 and 12 months, the number of
      relapses, and the duration of time until first relapse. RESULTS: After 12 weeks
      of treatment, no statistically significant differences were observed between the
      4 treatment combinations in any outcome measure. After 52 weeks, the only
      significant difference was observed in the amount of ethanol consumed, with the
      nefazodone + GC group showing higher alcohol intake than the other 3 groups.
      CONCLUSIONS: The results from this carefully designed clinical trial suggest that
      the 4 treatment combinations do not differ substantially in their efficacy for
      relapse prevention in nondepressed, severely alcohol-dependent patients.
      Nefazodone might even increase the risk of consuming a larger amount of ethanol
      per relapse in a subset of patients. CBT as performed in this study was
      associated with little additional benefit compared with structured GC.

PMID- 15491247
TI  - Clonidine in acute aversive inner tension and self-injurious behavior in female
      patients with borderline personality disorder.
AB  - BACKGROUND: States of strong aversive inner tension and dissociative symptoms are
      clinical hallmarks of borderline personality disorder and major reasons for self
      injurious behavior, a severe clinical condition for which there are no
      established pharmacologic treatment options. METHOD: The acute effect of 75 and
      150 microg of clonidine administered orally in acute states of strong aversive
      inner tension and urge to commit self-injurious behavior was examined in 14
      female patients meeting DSM-IV criteria for borderline personality disorder.
      Before and 30, 60, and 120 minutes after administration of clonidine, aversive
      inner tension and dissociative symptoms were assessed using a self-rating
      instrument for aversive inner tension and dissociation (Dissociation-Tension
      Scale acute), and the urge to commit self-injurious behavior and suicidal
      ideations were assessed using self-rating Likert scales. Blood pressure and heart
      rate were monitored during the trial. RESULTS: Aversive inner tension and urge to
      commit self-injurious behavior before administration of clonidine were strong.
      After administration of clonidine in both doses, aversive inner tension,
      dissociative symptoms, urge to commit self-injurious behavior, and suicidal
      ideations significantly decreased. The strongest effects were seen between 30 and
      60 minutes after drug intake and correspond to the pharmacokinetics of clonidine
      with maximum plasma concentrations after 1 hour. Blood pressure and aversive
      inner tension and dissociative symptoms were positively correlated before and
      after administration of clonidine. CONCLUSION: Orally given clonidine may be
      effective for treatment of acute states of aversive inner tension, dissociative
      symptoms, and urge to commit self-injurious behavior in female patients with
      borderline personality disorder. Further placebo-controlled studies with larger
      populations are needed to confirm this finding.

PMID- 15491248
TI  - Comparison of rapid-cycling and non-rapid-cycling bipolar I manic patients during
      treatment with olanzapine: analysis of pooled data.
AB  - INTRODUCTION: Rapid-cycling (RC) bipolar disorder patients experience high levels
      of morbidity, typically respond unsatisfactorily to available treatments, and,
      so, require additional studies of novel treatments. We report on the first
      controlled study comparing acute and continuous clinical outcomes in RC and non
      RC manic patients treated with olanzapine. METHOD: We analyzed data pooled from 2
      placebo-controlled, double-blind, 3- to 4-week trials of olanzapine in mania (N =
      254), 1 with an open-label extension up to 1 year (N = 113) and controlled
      supplementation with lithium or fluoxetine as needed, to compare demographic,
      clinical, and outcome measures between RC and non-RC subgroups of 254 DSM-IV
      bipolar I manic subjects. RESULTS: RC (N = 90, 35%) versus non-RC subjects (N =
      164, 65%) were younger at intake (p = .02), less often psychotic (p < .0001), and
      more likely to have familial bipolar disorder (p < .0001), abused substances (p =
      .01), more previous hospitalizations (p = .004), and many more illness episodes
      (p < .001). In initial blinded trial outcomes, relative responses (> or = 50%
      improvement of mania) to olanzapine/placebo were similar in RC and non-RC
      subjects, though early responses to olanzapine favored RC over non-RC subjects (p
      = .003), and long-term outcomes favored non-RC subjects (p = .05). Fewer RC
      subjects achieved strictly defined initial symptomatic remission (p = .014)
      within a year; RC subjects were more likely to experience recurrences (p = .002),
      especially of depressive illness (< .001), and had more rehospitalizations (p =
      .01) and suicide attempts (p = .03). CONCLUSIONS: RC bipolar I patients showed
      major initial differences and more rapid initial clinical changes, especially
      toward depression, with less favorable long-term outcomes than non-RC cases
      during treatment with olanzapine. Inclusion of RC bipolar disorder patients can
      complicate therapeutic trials, but these patients require further study for
      differential responsiveness to innovative treatments with methods of assessing
      clinical response that take their mood instability into account.

PMID- 15491249
TI  - Cardiopulmonary complications of ergot-derivative dopamine agonists.

PMID- 15491250
TI  - A relapse in pedophilic sex offending and subsequent suicide attempt during
      luteinizing hormone-releasing hormone treatment.

PMID- 15491252
TI  - A possible case of venlafaxine-induced Stevens-Johnson syndrome.

PMID- 15491253
TI  - A case of prolonged peyote-induced psychosis resolved by sleep.

PMID- 15491254
TI  - Personalizing politics: a congruency model of political preference.
AB  - Modern politics become personalized as individual characteristics of voters and
      candidates assume greater importance in political discourse. Although
      personalities of candidates capture center stage and become the focus of voters'
      preferences, individual characteristics of voters, such as their traits and
      values, become decisive for political choice. The authors' findings reveal that
      people vote for candidates whose personality traits are in accordance with the
      ideology of their preferred political party. They also select politicians whose
      traits match their own traits. Moreover, voters' traits match their own values.
      The authors outline a congruency model of political preference that highlights
      the interacting congruencies among voters' self-reported traits and values,
      voters' perceptions of leaders' personalities, politicians' self-reported traits,
      and programs of favored political coalitions.

PMID- 15491255
TI  - When clinical description becomes statistical prediction.
AB  - This article reconsiders the issue of clinical versus statistical prediction. The
      term clinical is widely used to denote 1 pole of 2 independent axes: the observer
      whose data are being aggregated (clinician/expert vs. lay) and the method of
      aggregating those data (impressionistic vs. statistical). Fifty years of research
      suggests that when formulas are available, statistical aggregation outperforms
      informal, subjective aggregation much of the time. However, these data have
      little bearing on the question of whether, or under what conditions, clinicians
      can make reliable and valid observations and inferences at a level of generality
      relevant to practice or useful as data to be aggregated statistically. An
      emerging body of research suggests that clinical observations, just like lay
      observations, can be quantified using standard psychometric procedures, so that
      clinical description becomes statistical prediction.

PMID- 15491256
TI  - How stigma interferes with mental health care.
AB  - Many people who would benefit from mental health services opt not to pursue them
      or fail to fully participate once they have begun. One of the reasons for this
      disconnect is stigma; namely, to avoid the label of mental illness and the harm
      it brings, people decide not to seek or fully participate in care. Stigma yields
      2 kinds of harm that may impede treatment participation: It diminishes self
      esteem and robs people of social opportunities. Given the existing literature in
      this area, recommendations are reviewed for ongoing research that will more
      comprehensively expand understanding of the stigma-care seeking link.
      Implications for the development of antistigma programs that might promote care
      seeking and participation are also reviewed.

PMID- 15491257
TI  - Attitudes in the fiber of everyday life: the discourse of racial evaluation and
      the lived experience of desegregation.
AB  - This article critically reviews the social-psychological literature on race
      attitudes, which has assumed that the prejudicial status of any expression is
      determined by the underlying psychological attitude that motivated it. Variation
      and inconsistency in individuals' attitudinal expressions and disagreement over
      how to measure prejudice have bedeviled attitude research. Contemporary theories
      of racial attitudes (symbolic racism, self-presentation, aversive racism) have
      responded to this problem by explaining how, when, and why attitudes vary and by
      proposing research paradigms for isolating prejudiced from nonprejudiced
      expressions. The authors argue that research in this area may be enhanced by the
      use of qualitative methods that place fewer constraints on the expression of
      racial attitudes and variability than quantitative methods do. Using empirical
      materials from a South African case study, the authors show that a focus on
      attitudinal discourse and the lived experience of desegregation allow researchers
      to investigate attitudes as social practices.

PMID- 15491264
TI  - Saving our psychosocial souls.

PMID- 15491265
TI  - Intended consequences.

PMID- 15491266
TI  - Facilitating objectivity when orchestrating the interaction between
      pharmacotherapy and psychotherapy.

PMID- 15491267
TI  - Concerns about professional schools.

PMID- 15491268
TI  - On the differences between academic research departments and professional
      schools.

PMID- 15491269
TI  - Evidence-based and intuition-based self-knowledge: an FMRI study.
AB  - Behavioral and neuropsychological studies have suggested multiple self-knowledge
      systems may exist (i.e., evidence-based and intuition-based self-knowledge);
      however, little is known about the nature of intuition-based self-knowledge. In a
      functional magnetic resonance imaging study, the neural correlates of intuition
      based and evidence-based self-knowledge were investigated. Participants with high
      and low experience in different domains (soccer and acting) made self
      descriptiveness judgments about words from each domain while being scanned. High
      experience domain judgments produced activation in a network of neural structures
      called the X-system, involved in automatic social cognition, whereas low
      experience domain judgments produced activations in a network called the C
      system, involved in effortful social cognition and propositional thought. The
      affective and slow-changing nature of intuition-based self-knowledge is
      discussed.

PMID- 15491270
TI  - A dual-process model of reactions to perceived stigma.
AB  - The authors propose a theoretical model of individual psychological reactions to
      perceived stigma. This model suggests that 2 psychological systems may be
      involved in reactions to stigma across a variety of social contexts. One system
      is primarily reflexive, or associative, whereas the other is rule based, or
      reflective. This model assumes a temporal pattern of reactions to the
      stigmatized, such that initial reactions are governed by the reflexive system,
      whereas subsequent reactions or "adjustments" are governed by the rule-based
      system. Support for this model was found in 2 studies. Both studies examined
      participants' moment-by-moment approach-avoidance reactions to the stigmatized.
      The 1st involved participants' reactions to persons with HIV/AIDS, and the 2nd,
      participants' reactions to 15 different stigmatizing conditions.

PMID- 15491271
TI  - Pseudocontingencies.
AB  - In 3 experiments, the authors explored a contingency illusion termed
      pseudocontingency (PC) that produces logically unwarranted but potentially useful
      inferences. PCs arise when bivariate contingencies are inferred from univariate
      distributions via heuristic alignment processes. For example, in the absence of
      information about the co-occurrence of TV habits and aggressive behavior within a
      school class, when the prevalence of both attributes is high, a teacher may infer
      a positive PC as if students who often watch TV were highly aggressive.
      Throughout 3 experiments, predictions of the level of 1 variable from the level
      of another served as a measure of PCs. The illusion could be evoked reliably
      whether information about target attributes was presented successively or
      simultaneously, whether common-cause or common-effect models were activated, and
      whether attributes involved 2 or more levels. The discussion centers on the
      cognitive processes underlying PCs and their origin and adaptive value.

PMID- 15491272
TI  - From seeing to being: subliminal social comparisons affect implicit and explicit
      self-evaluations.
AB  - The authors hypothesize that social comparisons can have automatic influences on
      self-perceptions. This was tested by determining whether subliminal exposure to
      comparison information influences implicit and explicit self-evaluation. Study 1
      showed that subliminal exposure to social comparison information increased the
      accessibility of the self. Study 2 revealed that subliminal exposure to social
      comparison information resulted in a contrast effect on explicit self-evaluation.
      Study 3 showed that subliminal exposure to social comparison information affects
      self-evaluations more easily than it affects mood or evaluations of other people.
      Studies 4 and 5 replicated these self-evaluation effects and extended them to
      implicit measures. Study 6 showed that automatic comparisons are responsive to a
      person's perceptual needs, such that they only occur when people are uncertain
      about themselves. Implications for theories of social cognition, judgment, and
      comparison are discussed.

PMID- 15491273
TI  - The person reference process in spontaneous trait inferences.
AB  - Five studies examined whether spontaneous trait inferences uniquely reference the
      person who performed a trait-implying behavior. On each study trial in 5 studies,
      participants saw 2 faces and a behavioral sentence referring to one of them.
      Later, participants saw face-trait pairs and indicated whether they had seen the
      trait word in the sentence presented with the face. Participants falsely
      recognized implied traits more when these traits were paired with actors' faces
      than with control faces. This effect was replicated for a large set effaces
      (120), after a week delay between study and recognition test, when equal
      attention was paid to each face, and when the orientation of the face at
      recognition was different from the orientation at encoding.

PMID- 15491274
TI  - Gender differences in automatic in-group bias: why do women like women more than
      men like men?
AB  - Four experiments confirmed that women's automatic in-group bias is remarkably
      stronger than men's and investigated explanations for this sex difference,
      derived from potential sources of implicit attitudes (L. A. Rudman, 2004). In
      Experiment 1, only women (not men) showed cognitive balance among in-group bias,
      identity, and self-esteem (A. G. Greenwald et al., 2002), revealing that men lack
      a mechanism that bolsters automatic own group preference. Experiments 2 and 3
      found pro-female bias to the extent that participants automatically favored their
      mothers over their fathers or associated male gender with violence, suggesting
      that maternal bonding and male intimidation influence gender attitudes.
      Experiment 4 showed that for sexually experienced men, the more positive their
      attitude was toward sex, the more they implicitly favored women. In concert, the
      findings help to explain sex differences in automatic in-group bias and
      underscore the uniqueness of gender for intergroup relations theorists.

PMID- 15491275
TI  - The interpersonal effects of emotions in negotiations: a motivated information
      processing approach.
AB  - Three experiments tested a motivated information processing account of the
      interpersonal effects of anger and happiness in negotiations. In Experiment 1,
      participants received information about the opponent's emotion (anger, happiness,
      or none) in a computer-mediated negotiation. As predicted, they conceded more to
      an angry opponent than to a happy one (controls falling in between), but only
      when they had a low (rather than a high) need for cognitive closure. Experiment 2
      similarly showed that participants were only affected by the other's emotion
      under low rather than high time pressure, because time pressure reduced their
      degree of information processing. Finally, Experiment 3 showed that negotiators
      were only influenced by their opponent's emotion if they had low (rather than
      high) power. These results support the motivated information processing model by
      showing that negotiators are only affected by their opponent's emotions if they
      are motivated to consider them.

PMID- 15491276
TI  - The relationship among expressions, labels, and descriptions of contempt.
AB  - This article reports 4 studies that demonstrate that the contempt expression is
      reliably associated with situations that elicit contempt and that the inability
      to label the contempt expression reflects a problem with its label or concept and
      not with the relationship between its expression and emotion. In Study I, the
      labeling of contempt in fixed-choice judgment tasks did not occur because of a
      process of elimination. In Studies 2 and 3, the contempt expression was
      associated with situations that elicit contempt, but participants did not label
      the situations in an open-ended response. In Study 3, participants also more
      reliably labeled the contempt expression with situations rather than with labels
      and did not generate contempt situations from labels. In Study 4, participants
      reported using, hearing, and reading about contempt the least among 7 emotions
      tested.

PMID- 15491277
TI  - Goal and personality trait development in emerging adulthood.
AB  - The present research examined continuity and change in the importance of major
      life goals and the relation between change in goals and change in personality
      traits over the course of college (N = 298). Participants rated the importance of
      their life goals 6 times over a 4-year period and completed a measure of the Big
      Five personality traits at the beginning and end of college. Like personality
      traits, life goals demonstrated high levels of rank-order stability. Unlike
      personality traits assessed during the same period and in the same sample, the
      mean importance of most life goals decreased over time. Moreover, each goal
      domain was marked by significant individual differences in change, and these
      individual differences were related to changes in personality traits. These
      findings provide insights into the relatively unstudied question of how life
      goals change during emerging adulthood.

PMID- 15491278
TI  - Essential role of ATF-1 in induction of NOX1, a catalytic subunit of NADPH
      oxidase: involvement of mitochondrial respiratory chain.
AB  - NADPH oxidase is the major source of superoxide production in cardiovascular
      tissues. We and others reported that PG (prostaglandin) F2alpha, PDGF (platelet
      derived growth factor) and angiotensin II cause hypertrophy of vascular smooth
      muscle cells by induction of NOX1 (NADPH oxidase 1), a catalytic subunit of NADPH
      oxidase. We found DPI (diphenylene iodonium), an inhibitor of flavoproteins,
      including NADPH oxidase itself, almost completely suppressed induction of NOX1
      mRNA by PGF2alpha or PDGF in a rat vascular smooth muscle cell line, A7r5.
      Exploration into the site of action of DPI using various inhibitors suggested the
      involvement of mitochondrial oxidative phosphorylation in PGF2alpha- or PDGF
      induced increase in NOX1 mRNA. In a luciferase reporter assay, activation of the
      CRE (cAMP-response element)-dependent gene transcription by PGF2alpha was
      attenuated by oligomycin, an inhibitor of mitochondrial F(o)F1-ATPase. Oligomycin
      and other mitochondrial inhibitors also suppressed PGF2alpha-induced
      phosphorylation of ATF (activating transcription factor)-1, a transcription
      factor of the CREB (CRE-binding protein)/ATF family. Silencing of the ATF-1 gene
      by RNA interference significantly reduced the induction of NOX1 by PGF2alpha or
      PDGF, while overexpression of ATF-1 recovered NOX1 induction suppressed by
      oligomycin. Taken together, ATF-1 may play a pivotal role in the up-regulation of
      NOX1 in rat vascular smooth muscle cells.

PMID- 15491279
TI  - Cephalopod vision involves dicarboxylic amino acids: D-aspartate, L-aspartate and
      L-glutamate.
AB  - In the present study, we report the finding of high concentrations of D-Asp (D
      aspartate) in the retina of the cephalopods Sepia officinalis, Loligo vulgaris
      and Octopus vulgaris. D-Asp increases in concentration in the retina and optic
      lobes as the animal develops. In neonatal S. officinalis, the concentration of D
      Asp in the retina is 1.8+/-0.2 micromol/g of tissue, and in the optic lobes it is
      5.5+/-0.4 micromol/g of tissue. In adult animals, D-Asp is found at a
      concentration of 3.5+/-0.4 micromol/g in retina and 16.2+/-1.5 micromol/g in
      optic lobes (1.9-fold increased in the retina, and 2.9-fold increased in the
      optic lobes). In the retina and optic lobes of S. officinalis, the concentration
      of D-Asp, L-Asp (L-aspartate) and L-Glu (L-glutamate) is significantly influenced
      by the light/dark environment. In adult animals left in the dark, these three
      amino acids fall significantly in concentration in both retina (approx. 25% less)
      and optic lobes (approx. 20% less) compared with the control animals (animals
      left in a diurnal/nocturnal physiological cycle). The reduction in concentration
      is in all cases statistically significant (P=0.01-0.05). Experiments conducted in
      S. officinalis by using D-[2,3-3H]Asp have shown that D-Asp is synthesized in the
      optic lobes and is then transported actively into the retina. D-aspartate
      racemase, an enzyme which converts L-Asp into D-Asp, is also present in these
      tissues, and it is significantly decreased in concentration in animals left for 5
      days in the dark compared with control animals. Our hypothesis is that the
      dicarboxylic amino acids, D-Asp, L-Asp and L-Glu, play important roles in vision.

PMID- 15491281
TI  - Abstracts of the 13th Congress of the European Academy of Dermatology and
      Venereology, 17-21 November 2004, Florence, Italy.

PMID- 15491282
TI  - A case of systemic histoplasmosis diagnosed in a peripheral blood smear.

PMID- 15491280
TI  - Distinctive activation mechanisms and functions for protein kinase Cdelta.
AB  - PKCdelta (protein kinase Cdelta) is a serine/threonine kinase that plays a key
      role in growth regulation and tissue remodelling. Traditional models of PKC
      activation have focused on lipid cofactors and anchoring proteins that localize
      the active conformation of PKCdelta to membranes, in close proximity with its
      target substrates. However, recent studies identify a distinct mode for PKCdelta
      activation involving tyrosine phosphorylation by Src family kinases. The tyrosine
      phosphorylated form of PKCdelta (which accumulates in the soluble fraction of
      cells exposed to oxidant stress) displays lipid-independent kinase activity and
      is uniquely positioned to phosphorylate target substrates throughout the cell
      (not just on lipid membranes). This review summarizes (1) recent progress towards
      understanding structure-activity relationships for PKCdelta, with a particular
      focus on the stimuli that induce (and the distinct functional consequences that
      result from) tyrosine phosphorylation events in PKCdelta's regulatory, hinge and
      catalytic domains; (2) current concepts regarding the role of tyrosine
      phosphorylation as a mechanism to regulate PKCdelta localization and actions in
      mitochondrial and nuclear compartments; and (3) recent literature delineating
      distinct roles for PKCdelta (relative to other PKC isoforms) in transcriptional
      regulation, cell cycle progression and programmed cell death (including studies
      in PKCdelta-/- mice that implicate PKCdelta in immune function and cardiovascular
      remodelling). Collectively, these studies argue that the conventional model for
      PKCdelta activation must be broadened to allow for stimulus-specific differences
      in PKCdelta signalling during growth factor stimulation and oxidant stress.

PMID- 15491283
TI  - Bone marrow granulomas in Salmonella paratyphi A infection.

PMID- 15491284
TI  - An infectious aetiology for childhood acute leukaemia: a review of the evidence.
AB  - There are three current hypotheses concerning infectious mechanisms in the
      aetiology of childhood leukaemia: exposure in utero or around the time of birth,
      delayed exposure beyond the first year of life to common infections and unusual
      population mixing. No specific virus has been definitively linked with childhood
      leukaemia and there is no evidence to date of viral genomic inclusions within
      leukaemic cells. The case-control and cohort studies have revealed equivocal
      results. Maternal infection during pregnancy has been linked with increased risk
      whilst breast feeding and day care attendance in the first year of life appear to
      be protective. There is inconclusive evidence from studies on early childhood
      infectious exposures, vaccination and social mixing. Some supportive evidence for
      an infectious aetiology is provided by the findings of space-time clustering and
      seasonal variation. Spatial clustering suggests that higher incidence is confined
      to specific areas with increased levels of population mixing, particularly in
      previously isolated populations. Ecological studies have also shown excess
      incidence with higher population mixing. The marked childhood peak in resource
      rich countries and an increased incidence of the childhood peak in acute
      lymphoblastic leukaemia (ALL) (occurring at ages 2-6 years predominantly with
      precursor B-cell ALL) is supportive of the concept that reduced early infection
      may play a role. Genetically determined individual response to infection may be
      critical in the proliferation of preleukaemic clones as evidenced by the human
      leucocyte antigen class II polymorphic variant association with precursor B-cell
      and T-cell ALL.

PMID- 15491285
TI  - Possibilities for tailored and targeted therapy in paediatric acute myeloid
      leukaemia.
AB  - The clinical outcome of acute myeloid leukaemia (AML) in children has improved
      considerably using intensive chemotherapy and/or stem cell transplantation. This
      leads to cure in 50-70% of patients, and also results in significant morbidity
      and mortality. Hence, we need other ways to improve the cure rate. This review
      discusses possibilities for tailored therapy, reviewing in vitro cellular drug
      sensitivity data. The results provide suggestions regarding the adaptation of
      clinical protocols in certain AML subgroups, although further clinical studies
      will show whether this is effective. Secondly, we review type 1 genetic
      abnormalities (such as receptor tyrosine kinase mutations) that result in
      enhanced survival and proliferation of leukaemic cells, which can be detected in
      approximately 50% of paediatric AML samples, and are non-randomly associated with
      French-American-British type and cytogenetic subgroups. FLT3 internal tandem
      duplication is associated with poor clinical outcome, and may be used for risk
      group stratification. The first results with small molecule inhibitors in adult
      AML do not suggest their use in children as yet. International collaboration is
      needed to further improve outcome by developing treatment protocols for subgroups
      of paediatric AML.

PMID- 15491286
TI  - Multiple myeloma involving central nervous system: high frequency of chromosome
      17p13.1 (p53) deletions.
AB  - Central nervous system (CNS) involvement is an unusual manifestation in multiple
      myeloma (MM). The molecular basis of CNS myeloma is poorly understood. MM is
      characterized by translocations involving the immunoglobulin heavy chain (IgH)
      locus and frequent 13q deletions. Alterations of p53 or c-myc in MM may represent
      secondary changes associated with disease progression. We investigated nine
      patients with CNS MM using interphase fluorescence in situ hybridization (FISH)
      combined with immunofluorescence detection of the cytoplasmic light chain (cIg
      FISH) for the presence of above genomic aberrations. Of nine patients studied,
      eight cases had hemizygous p53 deletion and 4 had 13q deletions. Of the patients
      with 13q deletions, two had IgH translocations, one involving 4p16.3 (FGFR3), the
      other involving 16q23 (c-maf). The high incidence of p53 deletions detected by
      cIg-FISH in CNS myeloma may be a marker for chromosomal instability, and may be
      associated with metastatic features of myeloma cells.

PMID- 15491287
TI  - Effects of PRIMA-1 on chronic lymphocytic leukaemia cells with and without
      hemizygous p53 deletion.
AB  - The tumour suppressor gene p53 is the most commonly mutated gene in solid
      tumours. Although less common in haematological malignancies, 10-15% of B-cell
      chronic lymphocytic leukaemia (B-CLL) cases carry a p53 mutation. Recently, the
      compound P53-dependent reactivation and induction of massive apoptosis (PRIMA-1)
      has been shown to induce cytotoxic effects and apoptosis in human tumour cells by
      restoration of the transcriptional activity of mutated p53. This is believed to
      be mediated by a change in the conformation of mutated p53 protein, restoring DNA
      binding and activation of p53 target genes. We studied the effects of PRIMA-1 and
      commonly used anti-leukaemic drugs on B-CLL cells from 14 patients with and
      without hemizygous p53 deletion. Cells obtained from peripheral blood or bone
      marrow were exposed to PRIMA-1 and fludarabine alone or in combination. PRIMA-1
      showed cytotoxic effects on B-CLL cells from samples with and without hemizygous
      p53 deletion. Furthermore, conventional B-CLL drugs were less effective in cell
      samples with hemizygous p53 deletion and the response depended on the size of the
      p53 deleted clone. Finally, we found evidence for synergistic and additive
      effects of PRIMA-1 in combination with fludarabine.

PMID- 15491288
TI  - Expression of protein gene product 9.5 (PGP9.5)/ubiquitin-C-terminal hydrolase 1
      (UCHL-1) in human myeloma cells.
AB  - The neuron cytoplasmic protein gene product 9.5 (PGP9.5)/ubiquitin-C-terminal
      hydrolase 1 (UCHL-1) protein is a thiol protease that recognizes and hydrolyzes a
      peptide bond at the C-terminal of ubiquitin, and is involved in the processing of
      ubiquitin precursors and ubiquinated proteins. Although this molecule is known as
      a specific tissue marker for the neuroendocrine system, many reports have
      indicated that PGP9.5 is a marker for certain tumour types, such as cancer of the
      lung, colon, and pancreas. The expression of PGP9.5 in myeloma cells was
      examined. PGP9.5 seemed to be expressed specifically in myeloma cells as compared
      with other haematological malignant cells. In addition, in myeloma cells
      subjected to growth-factor starvation, the upregulation of PGP9.5 was observed in
      association with that of p27(Kip1), a cyclin-dependent-kinase inhibitor, although
      the upregulation caused by irradiation was milder. In contrast, the hypoxic
      culture of myeloma cells induced down-regulation of PGP9.5. These results
      suggested that PGP9.5 may be a good marker for myeloma among haematological
      malignancies. In addition, it may indicate certain cellular features of myeloma
      cells, such as sensitivity to proteasome inhibitors.

PMID- 15491289
TI  - A population study to define the incidence and survival of multiple myeloma in a
      National Health Service Region in UK.
AB  - Epidemiology data on multiple myeloma (MM) occurrence and outcome is inconsistent
      whilst a major limitation of randomized controlled trials is selection bias. We
      present a population-based analysis of patients diagnosed with MM in the South
      Thames area, which comprises 5.4 million adult inhabitants. A total of 855 cases
      of MM were ascertained between 1999 and 2000 in a collaborative project involving
      haematologists and the Thames Cancer Registry. The age-standardized rate was 3.29
      per 100 000 and 4.82 cases per 100 000 (World Standard and European Population
      respectively). The median age was 73 years. The median survival for the whole
      group was 24 months whist it was 42 and 18 months in those aged less than 65
      years and greater than 65 years respectively (P < 0.001). This population study
      has shown a higher incidence than previously reported in the UK and Europe and
      provides a benchmark for future studies. If survival is to be improved, future
      clinical trials and health care planning should consider patients over 65 years
      of age.

PMID- 15491290
TI  - Prognostic significance of hepatocyte growth factor and c-MET expression in
      patients with diffuse large B-cell lymphoma.
AB  - The expression and prognostic significance of hepatocyte growth factor (HGF) and
      its receptor c-MET (MET proto-oncogene) was analysed in 96 cases of diffuse large
      B-cell lymphoma (DLBCL). Tissue sections were immunohistochemically stained for
      HGF and c-Met. The prognosis of HGF-positive and c-Met-positive cases was
      significantly worse than negative cases (HGF: P = 0.0036; c-Met: P = 0.0002). In
      addition, in the low-risk international prognostic index group, HGF-negative and
      c-Met-negative cases had a significantly better prognosis than positive cases
      (HGF: P = 0.0009; c-Met: P < 0.0001). Our results suggest that HGF/c-MET is a
      useful clinical marker of prognosis for patients with DLBCL.

PMID- 15491291
TI  - Presence of monoclonal free light chains in the serum predicts risk of
      progression in monoclonal gammopathy of undetermined significance.
AB  - We hypothesized that the presence of monoclonal free light chains (FLC) in the
      serum of patients with monoclonal gammopathy of undetermined significance (MGUS)
      is a marker of clonal evolution and a risk factor for progression. Forty-seven
      patients with MGUS and documented progression to myeloma or related malignancy
      were compared with 50 age- and gender-matched patients with MGUS and no evidence
      of progression after 5 or more years of follow-up. The presence of an abnormal
      kappa/lambda FLC ratio in the serum was associated with a higher risk of MGUS
      progression (relative risk 2.5; 95% confidence interval: 1.6-4.0; P < 0.001).

PMID- 15491292
TI  - Long-term disease-free survival of patients with advanced follicular lymphoma
      after allogeneic bone marrow transplantation.
AB  - Myeloablative allogeneic bone marrow transplantation (BMT) may be curative in
      patients with follicular non-Hodgkin's lymphoma, however, the impact of this
      therapy on long-term survival, disease progression and functional status is less
      clear. Twenty-nine patients (median age 42 years, range: 20-53) with advanced
      stage follicular lymphoma proceeded to allogeneic BMT a median of 25 (range: 8
      154) months postdiagnosis, between 1985 and 2001, and have been followed for a
      minimum of 2 years. Eleven of 29 (38%) had refractory disease (n = 5 induction
      failure, n = 6 resistant relapse). Most (27 of 29, 93%) received total body
      irradiation-based conditioning; stem cell source was marrow from a related donor
      (n = 20) or unrelated donor (n = 9). Seventeen of 29 patients (59%) were alive a
      median of 5 years (range: 2-11) post-BMT with a median Karnofsky Performance
      Score of 100%. Death occurred because of transplant complications in seven
      patients (cumulative incidence of non-relapse mortality 24%), and progressive
      lymphoma in five patients (cumulative incidence of refractory/recurrent lymphoma
      23%). The 5-year probability of overall and event-free survival was 58% and 53%
      respectively. Allogeneic BMT has resulted in long-term disease-free survival for
      approximately 50% of this cohort of patients with advanced follicular lymphoma
      and most of them now enjoy robust health.

PMID- 15491293
TI  - Measuring T cell immunity to influenza vaccination in children after haemopoietic
      stem cell transplantation.
AB  - Quantitative assessment of immunogen-specific T cell responses may provide a
      meaningful surrogate marker of functional immunity in patients following
      haemopoietic stem cell transplantation (HSCT). We developed a flow-cytometric
      assay to quantify antigen-specific T cell immunity to influenza-A and studied the
      T cell response to influenza vaccination in five children, 3-21 months post-HSCT.
      All patients showed an increase in influenza-A-specific CD4(+) immunity following
      vaccination while none had a detectable IgG response to the vaccine. This assay
      proved sufficiently sensitive to evaluate changes in T cell memory in
      immunocompromised individuals and could be used to better characterize post-HSCT
      immune reconstitution.

PMID- 15491295
TI  - Differential damage and recovery of human mesenchymal stem cells after exposure
      to chemotherapeutic agents.
AB  - Mesenchymal stem cells (MSCs) are an important cellular component of the bone
      marrow microenvironment for supporting haemopoiesis. However, their response to
      high-dose chemotherapy remains unknown. We assessed the acute direct effects of
      individual chemotherapeutic agents on human MSCs (hMSCs). Using an in vitro
      culture system, the chemosensitivity of hMSCs was determined by XTT (2,3-bis(2
      methoxy-4-nitro-5-sulphophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium
      hydroxide) assay in comparison with that of NB-4 cells, a leukaemic cell line,
      and normal peripheral blood mononuclear cells. The recovery of cell numbers
      following exposure to chemotherapeutic agents and chemotherapy-induced apoptosis
      of hMSCs were evaluated. Human MSCs were resistant to chemotherapeutic agents
      commonly used in bone marrow transplantation (BMT) (i.e. busulphan,
      cyclophosphamide and methotrexate). However, they were relatively sensitive to a
      panel of cytotoxic agents, such as paclitaxel, vincristine, etoposide and
      cytarabine. Furthermore, different recovery patterns were noted. There was
      sustained suppression in hMSCs following 3 d exposure to paclitaxel, cytarabine
      and etoposide. In contrast, significant recovery was seen in hMSCs treated with
      dexamethasone and vincristine respectively. Human MSCs have different patterns of
      response to a panel of chemotherapeutic agents commonly used in BMT or cancer
      therapy. Understanding this variation is important in optimizing conditioning
      regimens for BMT.

PMID- 15491294
TI  - Aberrant somatic hypermutation in post-transplant lymphoproliferative disorders.

PMID- 15491296
TI  - Expression pattern of FCRL (FREB, FcRX) in normal and neoplastic human B cells.
AB  - FCRL (also known as FREB and FcRX) is a recently described member of the family
      of Fc receptors for immunoglobulin G (IgG). In the present study we analysed its
      expression in normal and neoplastic lymphoid tissue using immunohistochemical
      techniques. FCRL was preferentially expressed in a proportion of germinal centre
      cells and, more weakly, in mantle zone B cells. In addition, strong labelling was
      observed in marginal zone B cells in the spleen, representing one of the few
      markers for this cell type. The majority of cases of small B-cell lymphoma,
      diffuse large B-cell lymphoma and lymphocyte predominance Hodgkin's disease were
      positive for FCRL. However, the number of positive cells varied widely, and in
      consequence we could not define a cut-off that distinguished subsets of diffuse
      large B-cell lymphoma. Our results also showed that FCRL tended to be negative in
      T-cell-rich B-cell lymphoma and in classical Hodgkin's disease. FCRL may
      therefore represent a novel marker for normal B cells (e.g. splenic marginal zone
      cells) and may also be useful as a potential marker of B-cell neoplasms.

PMID- 15491297
TI  - Human bone marrow adipocytes support complete myeloid and lymphoid
      differentiation from human CD34 cells.
AB  - In humans, the role of bone marrow (BM) adipocytes in supporting haematopoiesis
      has been questioned. A co-culture system of CD34(+) cells seeded onto either BM
      undifferentiated mesenchymal stem cells or differentiated adipocytes showed that
      BM adipocytes did not support the maintenance of immature progenitors but enabled
      their complete differentiation along the myeloid and lymphoid pathways. These
      properties appear to be opposite to those of osteoblasts, although both cell
      types share a common mesenchymal progenitor. These results suggest that stromal
      cells play a variety of roles in the haematopoietic microenvironment, which could
      be significant in situations such as osteoporosis or ageing.

PMID- 15491298
TI  - Myocardial iron clearance during reversal of siderotic cardiomyopathy with
      intravenous desferrioxamine: a prospective study using T2* cardiovascular
      magnetic resonance.
AB  - Heart failure from iron overload causes 71% of deaths in thalassaemia major, yet
      reversal of siderotic cardiomyopathy has been reported. In order to determine the
      changes in myocardial iron during treatment, we prospectively followed
      thalassaemia patients commencing intravenous desferrioxamine for iron-induced
      cardiomyopathy during a 12-month period. Cardiovascular magnetic resonance
      assessments were performed at baseline, 3, 6 and 12 months of treatment, and
      included left ventricular (LV) function and myocardial and liver T2*, which is
      inversely related to iron concentration. One patient died. The six survivors
      showed progressive improvements in myocardial T2* (5.1 +/- 1.9 to 8.1 +/- 2.8 ms,
      P = 0.003), liver iron (9.6 +/- 4.3 to 2.1 +/- 1.5 mg/g, P = 0.001), LV ejection
      fraction (52 +/- 7.1% to 63 +/- 6.4%, P = 0.03), LV volumes (end diastolic volume
      index 115 +/- 17 to 96 +/- 3 ml, P = 0.03; end systolic volume index 55 +/- 16 to
      36 +/- 6 ml, P = 0.01) and LV mass index (106 +/- 14 to 95 +/- 13, P = 0.01).
      Iron cleared more slowly from myocardium than liver (5.0 +/- 3.3% vs. 39 +/- 23%
      per month, P = 0.02). These prospective data confirm that siderotic heart failure
      is often reversible with intravenous iron chelation with desferrioxamine.
      Myocardial T2* improves in concert with LV volumes and function during recovery,
      but iron clearance from the heart is considerably slower than from the liver.

PMID- 15491299
TI  - Development of Duffy transgenic mouse: in vivo expression of human Duffy gene
      with -33T-->C promoter mutation in non-erythroid tissues.
AB  - Blood group Duffy gene (FY) promoter in Duffy-negative individuals contains a
      point mutation in the GATA1 protein-binding motif, which was suggested to be
      responsible for erythroid suppression of FY. We developed two transgenic mouse
      lines with FY from both Duffy phenotypes. Transgenic mice with FY from Duffy
      positive phenotype expressed Duffy protein both in red blood cells (RBCs) and non
      erythroid tissues. Transgenic mice with FY from Duffy-negative phenotype did not
      express Duffy protein in RBCs, but it was expressed in non-erythroid tissues.
      This is the first in vivo experimental evidence showing the effect of -33T-->C
      promoter mutation on FY expression.

PMID- 15491300
TI  - Prophylactic use of deferiprone (L1) and magnetic resonance imaging T2* or T2 for
      preventing heart disease in thalassaemia.

PMID- 15491302
TI  - PK Aarau: first homozygous nonsense mutation causing pyruvate kinase deficiency.

PMID- 15491303
TI  - Pain from myelofibrosis treated with regular pamidronate.

PMID- 15491304
TI  - Clonal karyotypic abnormalities in Philadelphia negative cells of CML patients
      treated with imatinib: is it under-reported and does it have any clinical
      significance?

PMID- 15491305
TI  - Prognostic factors for alveolar regeneration: bone formation at teeth and
      titanium implants.
AB  - OBJECTIVES: There is a limited understanding of the effect of defect
      characteristics on alveolar bone healing. The objectives of this study were to
      assess the effect of alveolar bone width and space provision on bone regeneration
      at teeth and titanium implants, and to test the hypothesis that the regenerative
      potentials at teeth and implants are not significantly different. METHODS:
      Critical size, 5-6-mm, supra-alveolar, periodontal defects were surgically
      created in 10 young adult dogs. Similarly, critical size, 5-mm, supra-alveolar,
      peri-implant defects were created in four dogs. A space-providing expanded
      polytetrafluoroethylene device was implanted for guided tissue
      regeneration/guided bone regeneration. The animals were euthanized at 8 weeks
      postsurgery. Histometric analysis assessed alveolar bone regeneration (height)
      relative to space provision by the device and the width of the alveolar crest at
      the base of the defect. Statistical analysis used the linear mixed models.
      RESULTS: A significant correlation was found between bone width and wound area
      (r=0.55892, p<0.0001). Generally, bone width and wound area had statistically
      significant effects on the extent of bone regeneration (p<0.0005 and p<0.0001,
      respectively). Bone regeneration was linearly correlated with the bone width at
      periodontal (p<0.001) and implant (p=0.04) sites, and with the wound area at
      periodontal (p<0.0001) and implant (p=0.03) sites. The relationships of bone
      regeneration with these two variables were not significantly different between
      teeth and implants (bone width: p=0.83; wound area: p=0.09). When adjusted for
      wound area, bone regeneration was significantly greater at periodontal than at
      implant sites (p=0.047). CONCLUSIONS: The horizontal dimension of the alveolar
      bone influences space provision. Space provision and horizontal dimension of the
      alveolar bone appear to be important determinants of bone regeneration at teeth
      and implants. The extent of alveolar bone formation at implant sites is limited
      compared with that at periodontal sites.

PMID- 15491306
TI  - Periodontal treatment of patients with Papillon-Lefevre syndrome: a 3-year follow
      up.
AB  - BACKGROUND/AIM: Conventional mechanical periodontal treatment of Papillon-Lefevre
      syndrome (PLS) has often been reported to fail. This study describes the outcome
      of a non-surgical periodontal therapy including antimicrobial treatment of nine
      patients diagnosed with PLS. The patients originate from a total of 15 children
      and adolescents with PLS for which clinical characteristics are presented.
      METHODS: Clinical examination including conventional periodontal measurements.
      Initial treatment including oral hygiene instruction, scaling and root planing
      and systemic amoxicillin-metronidazole therapy for 6 weeks. After that the
      patients were enrolled in a 3-month recall maintenance program. In addition to
      this mechanical supportive maintenance treatment, tetracycline was prescribed and
      used continuously for 1.5 years. RESULTS/CONCLUSION: On five patients who were
      showing acceptable standard of oral hygiene and also compliance with the
      antibiotic medication, development of periodontitis on erupting teeth was
      prevented and disease activity on the previously periodontally involved teeth
      controlled during a 3-year period. Poor results of treatment were observed for
      three patients, all siblings. These patients failed to comply with the medication
      and also failed to improve their oral hygiene.

PMID- 15491307
TI  - Long-term stability of periodontal conditions achieved following guided tissue
      regeneration with bioresorbable membranes: case series results after 6-7 years.
AB  - OBJECTIVES: To evaluate the results of guided tissue regeneration (GTR) treatment
      of intrabony defects with bioresorbable membranes after 6-7 years, and to
      disclose factors that may influence the long-term outcome of the treatment.
      METHODS: Twenty-five defects in 19 patients were treated by means of polylactic
      acid/citric acid ester copolymer bioresorbable membranes. At baseline and after 1
      and 6-7 years, the following parameters were recorded: (1) probing pocket depth
      (PPD), (2) gingival recession (REC), (3) probing attachment level (PAL)=PPD+REC,
      (4) presence/absence of plaque (PI), (5) presence/absence of bleeding on probing
      (BOP). Smoking habits and frequency of dental-control visits were also recorded.
      Significance of differences between categorical variables was evaluated with
      McNemar's test, and between numerical variables with the t-test for paired
      observations. Generalized linear models were constructed to evaluate the
      influence of various factors on PAL gain and PPD changes from 1 to 6-7 years.
      Association of smoking, frequency of dental controls, oral hygiene, and BOP with
      sites losing > or =2 mm in PAL was evaluated with Fisher's exact test. RESULTS:
      At baseline, a mean PPD of 8.7+/-1.1 mm and a mean PAL of 9.8+/-1.5 mm was
      recorded. Statistically significant clinical improvements were observed at 1 and
      6-7 years after GTR treatment. An average residual PPD of 3.8+/-1.1 mm and a mean
      PAL gain of 3.8+/-1.4 mm were observed after 1 year. After 6-7 years the
      corresponding values were 4.7+/-1.3 and 3.6+/-1.4 mm, respectively. There were no
      statistically significant differences between the 1- and the 6-7-year values. At
      the 6-7-year control, only 16% of the sites had lost > or =2 mm (maximum 3 mm),
      of the PAL gain obtained 1 year after GTR treatment. None of the sites had lost
      all of the attachment gained 1 year after treatment. Smoking, frequency of dental
      controls, oral hygiene, and BOP did not seem to influence the change of PPD and
      PAL gain, or the stability of PAL gain (i.e. losing PAL or not) from 1 to 6-7
      years from treatment. CONCLUSION: Clinical improvements achieved by GTR treatment
      of intrabony defects by means of bioresorbable membranes can be maintained on a
      long-term basis.

PMID- 15491308
TI  - Smoking affects the outcome of guided tissue regeneration with bioresorbable
      membranes: a retrospective analysis of intrabony defects.
AB  - OBJECTIVES: To disclose factors that may influence the results of guided tissue
      regeneration (GTR) treatment in intrabony defects with bioresorbable membranes.
      METHODS: Forty-seven intrabony defects in 32 patients were treated by means of
      polylactic acid/citric acid ester copolymer bioresorbable membranes. At baseline
      and after 1 year, the following parameters were recorded: (1) probing pocket
      depth (PPD), (2) gingival recession (REC), (3) probing attachment level
      (PAL)=PPD+REC, (4) presence/absence of plaque (PI), (5) presence/absence of
      bleeding on probing (BOP) and (6) intrabony component (IC) configuration (i.e.
      primarily presence of one, two, or three bone walls). Occurrence of membrane
      exposure and smoking habits were also recorded. Significance of differences
      between categorical variables was evaluated with McNemar's test, and between
      numerical variables with the t-test for paired observations. Generalized linear
      models were constructed to evaluate the influence of various factors on PAL gain
      and PPD after 1 year, including in the analysis only one defect per patient (i.e.
      32 defects) chosen at random. Odds ratios were calculated using the Mantel
      Haenszel method. Differences between smokers and non-smokers were evaluated by
      means of Pearson's chi2 and Student's t-test for non-paired observations.
      RESULTS: At baseline, a mean PPD of 8.6+/-1.1 mm and a mean PAL of 9.8+/-1.6 mm
      was recorded. Statistically significant clinical improvements were observed 1
      year after GTR treatment. An average residual PPD of 3.7+/-1.1 mm and a mean PAL
      gain of 3.8+/-1.5 mm were recorded. IC configuration and exposure of the membrane
      did not seem to influence the results, while a negative effect of smoking on the
      clinical parameters was observed. Smokers gained approximately 1 mm less in PAL
      than non-smokers (3.2+/-1.4 versus 4.3+/-1.3, respectively; p=0.03) and had
      approximately seven times less chances to gain 4 mm in PAL as compared with
      patients who did not smoke (odds ratio: 0.15). PPD reduction was less pronounced
      in smokers than in non-smokers (4.5+/-0.7 versus 5.5+/-0.7, respectively;
      p<0.01), resulting in somewhat deeper residual PPD in smokers than in non-smokers
      (3.6+/-1.0 versus 3.4+/-1.1; p>0.05). CONCLUSION: Smoking impairs the healing
      outcome of GTR treatment of intrabony defects with bioresorbable membranes.

PMID- 15491309
TI  - Periodontal attachment loss attributable to cigarette smoking in an urban
      Brazilian population.
AB  - AIMS: The present study estimated the percentages of cases with severe
      periodontal attachment loss (PAL) attributable to cigarette smoking in a
      representative adult urban population in southern Brazil. METHODS: A
      representative sample comprising 853 dentate individuals (age: 30-103 years) was
      selected by a multistage, probability sampling method. A full-mouth clinical
      examination of six sites per tooth was performed and an interview using a
      structured written questionnaire was undertaken. Cases were defined as
      individuals with > or =30% teeth with PAL > or =5 mm. A multivariate logistic
      regression analysis for complex surveys was performed, and adjusted for age,
      gender, race, socioeconomic status and dental calculus. RESULTS: The prevalence
      of cases in this population was 49.7%, or 739,000 subjects. Overall, 50.9% of
      this adult population, or approximately 757,000 subjects have had a lifetime
      exposure to cigarette smoking. Multivariate analysis showed that heavy and
      moderate smokers had a significantly higher risk for PAL > or =5 mm than non
      smokers (odds ratio=3.6, 2.0, respectively) after adjusting for the above
      covariates. We estimated that the number of moderate and heavy smokers with > or
      =30% teeth with PAL > or =5 mm might be reduced by approximately 28% and 48%,
      respectively, had they not smoked cigarettes. We project that a smoking cessation
      program could result in a reduction in the number of cases by up to 12% in this
      population, or approximately 90,000 potential cases. CONCLUSION: Cigarette
      smoking was strongly associated with severe attachment loss in this population. A
      significant percentage of cases may have been prevented if smoking cessation
      interventions had been implemented. The results support the implementation of
      population-based smoking cessation programs to reduce the prevalence of severe
      attachment loss in populations with high level of smoking exposure.

PMID- 15491310
TI  - Polymorphisms in genes coding for enzymes metabolizing smoking-derived substances
      and the risk of periodontitis.
AB  - OBJECTIVES: Although the direct cause for periodontitis is oral bacterial
      infection, its progression depends upon genetic and environmental factors.
      Smoking, one of the environmental factors, is a risk factor for the development
      and severity of periodontitis. Therefore, individual susceptibility to
      periodontitis may be influenced by the polymorphisms of genes coding for enzymes
      metabolizing tobacco-derived substances. The object of this study is to
      investigate roles of genetic polymorphisms of these metabolizing enzymes in the
      risk for periodontitis. MATERIAL AND METHODS: We investigated three important
      enzymes: cytochrome P450 (CYP) 1A1, CYP2E1 and glutathione S-transferase (GST)
      M1, involved in the metabolic activation and detoxification of tobacco-derived
      substances. The prevalence of the polymorphisms of these genes was examined in
      115 patients with periodontitis as well as in 126 control subjects. RESULTS:
      Significantly increased risk for periodontitis was observed for subjects with the
      polymorphic CYP1A1 m2 allele (odds ratio (OR)=2.3, 95% confidence interval
      (CI)=1.2-4.4). A significant risk increase for periodontitis associated with the
      GSTM1 allele was observed (OR=2.1, 95% CI=1.3-3.6). However, no association was
      observed between the CYP2E1 Pst1 polymorphism and risk for periodontitis (OR=1.3,
      95% CI=0.6-2.5). CONCLUSION: These results suggest that the GSTM1 and CYP1A1
      polymorphisms may play an important role in risk for periodontitis.

PMID- 15491311
TI  - Amine fluoride/stannous fluoride and incidence of root caries in periodontal
      maintenance patients. A 2 year evaluation.
AB  - AIM: The purpose of the present study was to evaluate in a group of periodontal
      maintenance patients, the effect of using a dentifrice and mouthrinse containing
      amine fluoride (AmF) and stannous fluoride (SnF2) as compared with a dentifrice
      and mouthrinse both containing sodium fluoride (NaF) with regard to their root
      caries experience. MATERIAL: In total, 80 patients who had been treated for
      moderate-to-severe periodontitis agreed to participate in this study. Subjects
      received supportive periodontal therapy at regular intervals of 3-4 months for at
      least a period of 1 year. The patients were randomly divided into two groups: (1)
      the test group used an AmF/SnF2 dentifrice and mouthrinse and (2) the control
      group used an NaF-containing dentifrice and mouthrinse. Root caries was recorded
      at four sites per tooth at baseline and 24 months. RESULTS: An increase in number
      of the exposed root surfaces was noted for both groups during the experimental
      period (p<0.05). The mean number of active caries lesions at baseline was 2.1 and
      1.8 for the test group and control group, respectively. At 24 months, the
      corresponding values were 1.8 for the test and 2.2 for the control group. An
      increase of the mean number of restored surfaces was noted for the AmF/SnF2 group
      (from 7.3 to 13.4) and the control group (from 7.9 to 14.7) during the course of
      the study. This increase was found to be statistically significant for both
      groups in comparison with the baseline values (p< or =0.01). No statistically
      significant differences were noted between groups. Further analysis of the
      restored surfaces revealed that the major increase in number of the restorations
      was associated with restorations involving three to four root surfaces in the
      same tooth. Molars and premolars were the teeth receiving most new restorations.
      CONCLUSION: The present study did not detect a difference in terms of root caries
      development between the two groups. Root caries development is a common finding
      associated with surfaces developing recession in patients once treated for
      periodontal problems.

PMID- 15491312
TI  - The effect of periodontal treatment on the salivary bacterial load and early
      plaque formation.
AB  - AIM: The purpose of the present study was to investigate in periodontitis
      patients the relationship between the number of bacteria in the saliva and the
      amount of de novo plaque formation before and after treatment. METHODS: At
      baseline, before any treatment was provided, patients rinsed with 10 ml sterile
      saline. After professional tooth cleaning the patients were instructed to abolish
      all tooth cleaning procedures for the subsequent 24 h. After this period, the
      rinsing procedure was repeated and the amount of de novo plaque was assessed.
      Three months after the initial periodontal therapy was completed the experiment
      was repeated. The microbiological evaluation of the rinsing samples was carried
      out by means of phase contrast microscopy and anaerobic culturing. RESULTS: After
      treatment the amount of de novo plaque was less compared to before treatment,
      0.40 and 0.65 respectively. Both before and after treatment more de novo plaque
      was present at sites with inflammation than at healthy sites. In order to
      evaluate the contribution of the numbers of salivary bacteria to the amount of de
      novo plaque formation an analysis was carried out for healthy sites. This
      analysis included only healthy sites as determined before treatment and the same
      sites after treatment. The results showed a significant reduction in the de novo
      plaque formation after treatment (0.49 before and 0.22 after treatment). Phase
      contrast microscopic evaluation showed that the number of bacteria in the rinsing
      samples after treatment was less than before treatment. After treatment also a
      reduction was found in the prevalence of Prevotella intermedia, Tannerella
      forsythensis and Peptostreptococcus micros in the rinsing samples. CONCLUSION:
      The present study confirms the observation in the literature that the periodontal
      condition is of major importance in the rate of de novo plaque formation. In
      addition, the results suggest that the number of bacteria in the saliva may play
      a role.

PMID- 15491313
TI  - Myeloid-related protein (MRP)8/14 (calprotectin) and its subunits MRP8 and MRP14
      in plaque-induced early gingival inflammation.
AB  - BACKGROUND: The inflammatory myeloid-related protein, MRP8/14, also called
      calprotectin, and its subunits MRP8 and MRP14 have been detected and identified
      recently in gingival crevicular fluid (GCF). It has been suggested that the type
      and phase of inflammation can be discriminated on the basis of differences in the
      expression of calprotectin and its subunits, released during activation and/or
      death of granulocytes and monocytes. The purpose of this study was to quantify
      calprotectin and its subunits (MRPs) simultaneously in the GCF during the initial
      phase of experimentally induced gingivitis, and to examine their inter- and intra
      individual variations. MATERIAL AND METHODS: Fifteen healthy non-smoking
      subjects, aged 18-30, were involved in this study. An initial hygiene phase (days
      -11 to 0) was followed by 10 days of undisturbed plaque accumulation. At days 
      11, -3, 0, 10, 11, clinical parameters were recorded and GCF samples collected
      with Durapore strips from 12 sites in each subject. Quantitative analyses of
      total proteins, MRP8/14, MRP14 and MRP8 were performed by ELISA procedures.
      RESULTS: During the experimental phase with no oral hygiene (days 0-10), the
      clinical parameters Plaque Index, Gingival Index (GI) and bleeding on probing
      increased as expected, confirming that plaque accumulation leads to gingival
      inflammation. Levels of the MRPs were individually variable. They increased with
      plaque accumulation in one-half of the subjects, and decreased in the other
      subjects. The levels of MRP8/14 and MRP14 at subject recruitment (day -11) could
      predict a significant part of the GI at day 10. Only minute amounts of the
      subunits MRP8 and MRP14 were detected in comparison with the complex MRP8/14
      throughout the experiment. Considerable variations were noted among sites within
      subjects. CONCLUSION: The expression of calprotectin in the early phase of
      experimental gingivitis is variable between subjects, and two groups of subjects
      can be differentiated according to their response patterns. Clinical parameters
      at the very first visit (day -11) seemed to be different in the two response
      groups. The results of the present investigation indicate that the inflammatory
      response to plaque accumulation depends on the initial status of the subjects,
      which may not be leveled out by the introduction of perfect oral hygiene. Whether
      these patterns reflect a different susceptibility to periodontal diseases remains
      to be determined.

PMID- 15491314
TI  - Longitudinal stability of serum immunoglobulin G responses to periodontal
      bacteria.
AB  - BACKGROUND: The value of seroepidemiology in the study of periodontal infections
      has not been adequately explored. This study examined serum immunoglobulin (IgG)
      responses to periodontal bacteria in patients with periodontitis and
      periodontitis-free individuals over a 30-month period. METHODS: Eighty-nine
      patients with chronic periodontitis and 42 control subjects with no deep
      periodontal pockets and no or minimal attachment loss (30-72 years old, 43% men)
      were included. Patients were examined at baseline, after completed periodontal
      therapy 4 months post-baseline, and at 30 months, and controls, at baseline and
      30 months. IgG antibodies to 19 periodontal species were determined by
      checkerboard immunoblotting. RESULTS: On average, patients displayed at baseline
      up to 800-fold higher titers than controls to all but three species. Over the 30
      month period, titers remained stable at low levels in controls. In patients,
      periodontal conditions improved from a baseline mean probing depth of 3.6 mm,
      bleeding on probing of 62% and an average of 21.5 pockets of=6 mm/person, to 2.5
      mm mean pocket depth, 30% bleeding on probing, and 1.2 deep pockets, at 30
      months. Over time, antibody titers showed a modest decline in patients, but
      remained significantly elevated at 30 months in comparison with controls.
      Antibody-level changes over time were not significantly different between
      subjects that did and did not receive adjunctive systemic antibiotics.
      CONCLUSIONS: Conspicuous differences in IgG titers to periodontal bacteria exist
      between periodontitis patients and periodontally healthy controls. Despite
      successful periodontal therapy, titers remained elevated over a 30-month period,
      suggesting that serology may mark the history of past periodontal infection.

PMID- 15491315
TI  - The CD14 -159C-to-T promoter polymorphism in periodontal disease.
AB  - BACKGROUND: A single-nucleotide promoter polymorphism in the CD14 gene was
      associated with various inflammatory conditions. The present study sought to
      determine the frequency of the CD14 -159C-to-T polymorphism among subjects with
      periodontitis and healthy control individuals. METHODS: A total of 70 patients
      with periodontal disease and 75 healthy controls were genotyped for the CD14 
      159C-to-T polymorphism. Genotyping was performed by polymerase chain reaction and
      restriction fragment length polymorphism analysis. The allele frequencies and
      distribution of genotypes within both study groups were compared using Fisher's
      exact test at a level of significance of 5% (p<0.05). RESULTS: Overall, the
      frequency for the CD14 -159T allele in patients with periodontitis was 39.3%
      (55/140) and 48.0% (72/150) for the controls (p=0.135). The CD14 -159C allele was
      significantly more prevalent (p=0.013) among females with periodontitis (33.3%;
      24/72) as compared with healthy control subjects (55.6%; 30/54). In contrast, the
      distribution of the CD14 -159C-to-T polymorphism showed no significant difference
      among males with and without periodontitis (p=0.816). CONCLUSION: Herein, the C 
      159T promoter polymorphism of the CD14 gene was associated in female but not in
      male patients with periodontal disease.

PMID- 15491316
TI  - Subgingival microbiota of chronic periodontitis subjects from different
      geographic locations.
AB  - BACKGROUND: Most clinical studies assume that the subgingival microbiota is
      similar from one geographic location to another. The purpose of the present
      investigation was to examine the composition of the subgingival microbiota in
      chronic periodontitis subjects from four countries. METHOD: Subjects with chronic
      periodontitis (N, Sweden=101; USA=115; Brazil=58; Chile=26) were recruited.
      Subjects were measured at baseline for plaque, gingivitis, bleeding on probing
      (BOP), suppuration, pocket depth (PD) and attachment level (AL) at six sites per
      tooth. Subgingival plaque samples taken from the mesial aspect of each tooth at
      baseline were individually analyzed for their content of 40 bacterial species
      using checkerboard DNA-DNA hybridization (total samples=6036). % DNA probe counts
      comprised by each species was determined for each site and averaged across sites
      in each subject. Significance of differences in proportions of each species among
      countries was determined using ancova adjusting for age, mean pocket depth,
      gender and smoking status. p-Values were adjusted for multiple comparisons.
      RESULTS: On average, all species were detected in samples from subjects in the
      four countries. Thirteen species differed significantly in adjusted mean
      proportions among countries even after adjusting for multiple comparisons.
      Porphyromonas gingivalis, one species that differed in proportions among
      countries, comprised adjusted means of 7.5, 11.9, 1.6 and 6.6% of the microbiota
      in subjects from Brazil, Chile, Sweden and USA (p<0.001), while mean proportions
      of Treponema denticola were 6.7, 4.2, 0.8 and 2.3, respectively (p<0.001). In
      contrast, a key periodontal pathogen, Tannerella forsythensis, exhibited mean
      proportions ranging from 6.2-8.5% and did not differ significantly among
      countries. Besides these species, prominent species in Brazil were Actinomyces
      naeslundii genospecies 1 and 2 (8.4%, 7.2%) and Prevotella intermedia (6.5%); in
      Chile, Prevotella melaninogenica (6.4%) and Neisseria mucosa (5.3%); in Sweden A.
      naeslundii genospecies 2 (8.4%), Capnocytophaga gingivalis (7.1%) and
      Peptostreptococcus micros (5.0%); in USA A. naeslundii genospecies 2 (7.5%), P.
      intermedia (6.8%) and C. gingivalis (6.1%). CONCLUSIONS: The microbial profiles
      of subgingival plaque samples from chronic periodontitis subjects in four
      countries showed surprisingly marked differences. These differences persisted
      after adjusting for age, mean pocket depth, gender and smoking status.

PMID- 15491317
TI  - Significant influence of scaler tip design on root substance loss resulting from
      ultrasonic scaling: a laserprofilometric in vitro study.
AB  - OBJECTIVES: Ultrasonic scalers have become increasingly popular for subgingival
      debridement. The aim of the present study was to investigate the influence of
      different working tip designs (narrow versus wide) on root substance loss caused
      by either magnetostrictive or piezoelectric ultrasonic devices. METHODS: In this
      in vitro study, a magnetostrictive ultrasonic system with either Slimline or TFI
      10 inserts and a piezoelectric ultrasonic system with either Perioprobe or Type-A
      inserts were compared at different application forces. Loss of root dentin was
      determined by defect width, defect depth and defect volume resulting from
      standardized instrumentation using laser profilometry. RESULTS: There were
      consistent and statistically significant differences between all groups. The mean
      observed dentin alterations for the magnetostrictive ultrasonic device operating
      a Slimline insert at a lateral force of 0.3 N were 254.4 microm, 6.3 microm and
      22.5 microm3 and for the TFI-10 tip 759.0 microm, 23.5 microm and 160.2 microm3
      for the parameters defect width, depth and volume, respectively. For the
      piezoelectric ultrasonic system operating a Perioprobe insert, the corresponding
      mean values were 352.0 microm/12.1 microm/56.4 microm3 and for the universal Type
      A insert they were 402.4 microm/14.0 microm/133.4 microm3. With application
      forces of 0.7 N, root substance removal increased up to twofold. CONCLUSION: The
      present investigation could demonstrate that the aggressiveness of
      magnetostrictive and piezoelectric ultrasonic devices to root substance was
      significantly influenced by the scaler tip designs, increasing for wider scaler
      tips as compared with narrow, probe-shaped inserts.

PMID- 15491318
TI  - Efficacy of plaque removal of the Sonicare Elite versus the Sonicare Advance from
      hard-to-reach sites.
AB  - OBJECTIVE: To compare the Sonicare Elite with the Sonicare Advance in terms of
      the reduction in supragingival plaque in the posterior, hard-to-reach areas of
      the mouth. METHOD: This was a single-cohort, 6-week, two-treatment, single-blind,
      cross-over clinical trial that recruited 45 subjects. Plaque scores were recorded
      throughout the study using a modification of the Quigley and Hein plaque index
      (PI). All subjects had a minimum pre-brushing PI of 1.8 at screening following 24
      h abstention from tooth cleaning. Subjects then used a Sonicare Advance powered
      toothbrush at home for 4 weeks for familiarisation purposes. At the next visit
      (2), subjects were given either the Sonicare Elite or the Sonicare Advance
      powered toothbrush for a further 2 weeks of home use. Twenty-four hours prior to
      visit 3, subjects abstained again from tooth cleaning. At visit 3, the PI was
      recorded pre- and post-tooth brushing and then all remaining "mature" plaque was
      removed professionally with a dental prophylaxis. After a further period of 24 h
      (to accumulate new plaque) without tooth brushing the subjects returned for visit
      4 at which PIs were again recorded pre- and post-tooth brushing. The subjects
      were then given the second toothbrush in the cross-over sequence and attended for
      visits 5 and 6 at which the protocol for visits 3 and 4 was repeated. RESULTS:
      The Sonicare Elite powered toothbrush was more effective than the Sonicare
      Advance model in removing both mature and newly formed plaque. The magnitude of
      the differences between the toothbrushes for all posterior sites, interproximal
      and smooth surfaces, respectively, was 0.35 U (p<0.001), 0.39 U (p<0.001) and
      0.32 U (p<0.001) of the modified Quigley and Hein PI. There was no evidence of a
      significant period effect comparing data from visits 5 and 6 against those from
      visits 3 and 4. There was, however, a significant visit effect with full-mouth
      (p<0.01), interproximal (p<0.001) and smooth surface (p<0.01) post-brushing
      plaque scores being significantly lower at visits 4 and 6 than at visits 3 and 5.
      CONCLUSION: The data support the observation that the Sonicare Elite toothbrush
      is more effective than the Sonicare Advance model in removing both newly formed
      and mature plaque from all posterior, interproximal and smooth tooth surfaces.

PMID- 15491319
TI  - Effects of post-surgical cleansing protocols on early plaque control in
      periodontal and/or periimplant wound healing.
AB  - OBJECTIVE: The aim of this RCT was to evaluate early wound healing following
      specific post-surgical care protocols. MATERIAL AND METHODS: Following
      periodontal flap surgery, 60 patients were randomly assigned to follow one of two
      post-surgical protocols. Subjects smoking >20 cigarettes per day were excluded.
      Patients following the control protocol rinsed twice daily for 1 min with 0.1% of
      chlorhexidine (CHX) for 4 weeks. In addition to CHX rinsing, patients assigned to
      the test protocol applied CHX locally using a special very soft surgical
      toothbrush (Chirugia) from days 3 to 14, and a soft toothbrush (Ultrasuave) from
      days 14 to 28, twice daily. Baseline measurements included gingival crevicular
      fluid (GCF) flow rate, probing depth, probing attachment level, presence of
      bleeding on probing and full-mouth plaque score. Measurements were repeated at 1,
      2 and 4 weeks after surgery. RESULTS: Both post-surgical protocols resulted in
      successful wound healing and optimal wound closure at 4 weeks. There were no
      statistical differences in the GCF flow rate between test and control protocols.
      There was a lower incidence of recession of > or =2 mm following the test
      protocol. CONCLUSION: The use of specific post-surgical cleansing protocols
      including the introduction of mechanical cleansing at day 3, using local
      application of CHX in addition to daily rinsing with CHX may be recommended.

PMID- 15491320
TI  - Life-threatening thrombotic thrombocytopenic purpura associated with dental foci.
      Report of two cases.
AB  - OBJECTIVES: Thrombotic thrombocytopenic purpura (TTP) is a rare haematological
      disease of unknown aetiology. This thrombotic microangiopathy is characterized by
      microvascular lesions with platelet aggregation. It is found in adults and can be
      associated with pregnancy, cancer, autoimmune diseases, bone marrow
      transplantation, drugs and bacterial as well as viral infections. The therapy
      requires a multi-disciplinary team approach involving dentistry. Even if TTP is
      immediately treated in an adequate manner, it still shows a mortality of up to
      20%. AIM: To define a specific treatment concept for periodontal disease and
      decayed teeth in patients suffering from TTP based on the experiences gained from
      two cases. CONCLUSION: The two patient cases revealed a possible association of
      TTP with dental foci. Because of the severity and mortality of this disease, both
      prognosis evaluation and treatment standards of periodontologically compromised
      or decayed teeth have to be strictly followed in patients suffering from TTP. In
      order to avoid recurrence of TTP, it seems important to remove radically teeth of
      questionable prognosis.

PMID- 15491321
TI  - Long-term vertical changes of the anterior maxillary teeth adjacent to single
      implants in young and mature adults. A retrospective study.
AB  - AIM: To evaluate the effects of the tooth eruption process on the position of
      teeth adjacent to implant-borne restorations in adult patients compared to
      patients in their late adolescence. SUBJECT AND METHODS: The sample included 28
      patients divided into two groups. A "young adult" group consisting of 14
      patients, aged from 15.5 to 21 years, and a "mature adult" group consisting of 14
      patients, aged from 40 to 55 years. All patients presented missing anterior
      teeth, requiring insertion of 40 implant fixtures (16 central incisors, 12
      lateral incisors, 12 canines). The implants were of the Straumann Dental Implant
      System, clinically and radiologically re-evaluated 1 year or more after the
      surgical procedure (mean interval=4.2 years). Assessment of the eruption of the
      adjacent teeth was performed using the implant as a stable point of reference:
      measurements of the different reference points were compared after implant
      placement and at follow-up examination. RESULTS: In the "young adult" group, all
      patients showed infra-occlusion of the implant-supported crowns: the vertical
      step measured on radiographs varied between 0.1 and 1.65 mm. In the "mature
      adult" group, all patients showed a vertical difference between the teeth
      adjacent to the implant-supported crown and the implant: the measured step ranged
      from 0.12 to 1.86 mm. No difference was found in the amount of vertical eruption
      between male and female patients, nor according to localization of the implant.
      CONCLUSION: Mature adults can exhibit major vertical steps after anterior
      restorations with osseointegrated fixtures to the same extent as adolescents or
      "young adult" individuals with residuous growth potential.

PMID- 15491322
TI  - Skp2 and p27kip1 expression in melanocytic nevi and melanoma: an inverse
      relationship.
AB  - BACKGROUND: S-phase kinase associated protein-2 (Skp2) ubiquitin ligase p45(SKP2)
      is important in the degradation of p27kip1 (a cyclin dependent kinase inhibitor)
      and progression through the G1-S cell-cycle checkpoint. Low levels of p27 and
      high levels of Skp2 are related to poor prognosis in some cancers. METHODS:
      Clinicopathologic features and immunohistochemical expression of Skp2 and p27kip1
      were investigated in 198 melanocytic proliferations: 21 melanocytic nevi, 23
      melanoma in situ, 119 primary melanoma, and 35 metastatic melanoma samples.
      Comparative and survival analyses were performed. RESULTS: Progressive and
      significant increases and decreases in the nuclear expression of Skp2 and
      p27kip1, respectively, was identified moving from melanocytic nevi (0.05 +/-
      0.2/85 +/- 15) to melanoma in situ (3 +/- 2/45 +/- 20) to primary cutaneous
      melanoma (12 +/- 9/30 +/- 25) to metastatic melanoma (25 +/- 15/15 +/- 20) (p <
      or = 0.006). Expression of these proteins also significantly correlated with
      increasing American Joint Committee on Cancer (AJCC) T (tumor) classification and
      AJCC stage (p < or = 0.01). Moreover, the level of these two proteins exhibited a
      significant inverse relationship (r = -0.4, p = 0.0001). Skp2 cytoplasmic
      labeling index of >20% predicted worse 10-year overall survival (38% vs. 86%, p =
      0.04) in primary melanoma. Neither p27 nor Skp2 nuclear expression impacted
      significantly on prognosis. CONCLUSIONS: Gain of Skp2 and loss of p27kip1 protein
      expression are implicated in melanoma progression where the level of p27kip1 may
      be regulated by targeted proteolysis via Skp2. Cytoplasmic expression of Skp2
      defines a subset of aggressive melanomas and could represent another pathway of
      deregulation of the cell cycle.

PMID- 15491323
TI  - Analysis of p53 and bcl-2 protein expression in the non-tumorigenic,
      pretumorigenic, and tumorigenic keratinocytic hyperproliferative lesions.
AB  - BACKGROUND: The hyperproliferative keratinocytic lesions encompass a wide range
      of non-tumorigenic, pretumorigenic, and tumorigenic conditions. The aim of this
      work was to examine the expression patterns of apoptosis-linked molecules (bcl-2
      and p53) in these lesions. METHODS: Immunoperoxidase staining methods were
      applied to analyze p53 and bcl-2 protein expression in a total of 66 cases,
      including 12 squamous cell carcinomas (both in situ and invasive SCC), 11 actinic
      keratoses (AK), 13 psoriasis vulgaris (PV), eight verruca vulgaris (VV), six
      chronic dermatitis (CD), five seborrheic keratosis (SK), four lichen planus (LP),
      three epidermodysplasia verruciformis (EDV), two condyloma acuminata (CA), two
      lichen simplex chronicus (LSC), and 10 specimens from normal skin. RESULTS: As
      compared to normal skin (0.70 +/- 0.26), the bcl-2 average weighted scores in the
      non-tumorigenic (0.76 +/- 0.16), pretumorigenic (1.45 +/- 0.28), and tumorigenic
      lesions (2.83 +/- 0.50 and 2.92 +/- 0.50 for in situ and invasive SCC,
      respectively) showed significant up-regulation (p = 0.001). In the non
      tumorigenic lesions, the bcl-2 expression values decreased in the following
      order: SK > EDV > CD > LP > CA > PV > VV (1.40 +/- 0.24 > 1.33 +/- 0.67 > 0.83 +/
      0.40 > 0.67 +/- 0.21 > 0.50 +/- 0.20 > 0.46 +/- 0.22 > 0.13 +/- 0.01,
      respectively). As compared to normal skin (1.10 +/- 0.23), the p53 average
      weighted scores in the non-tumorigenic (1.86 +/- 0.18), pretumorigenic (3.64 +/-
      0.53), and tumorigenic lesions (5.00 +/- 1.00 and 5.08 +/- 0.86 for in situ and
      invasive SCC, respectively) showed significant up-regulation (p = 0.021). In the
      non-tumorigenic lesions, p53 average weighted scores decreased in the following
      order: SK > PV > CA > LP > CD > VV > EDV (3.20 +/- 0.49 > 2.38 +/- 0.27 > 2.0 +/-
      0.0 > 1.83 +/- 0.48 > 1.0 +/- 0.37 > 1.0 +/- 0.33 > 1.0 +/- 0.0, respectively).
      There was a positive correlation between bcl-2 and p53 protein expression in
      normal skin (r = 0.966, p = 0.0001), non-tumorigenic (r = 0.775, p = 0.0001),
      pretumorigenic (r = 0.830, p = 0.001), and tumorigenic lesions (r = 0.757, p =
      0.003). CONCLUSIONS: Bcl-2 and p53 proteins are altered in the keratinocytic
      hyperproliferative lesions. Determination of whether these alterations reflect
      underlying gene mutations will require further investigations.

PMID- 15491324
TI  - Evaluation of anti-thrombomodulin antibody as a tumor marker for vascular
      neoplasms.
AB  - BACKGROUND: Various endothelial markers are available for the evaluation of
      vascular tumors and malformations, including anti CD34, anti-CD31, von Willebrand
      factor (vWF), and anti-thrombomodulin (anti-TM) antibodies. All have their
      limitations, and we sought to compare the utility of anti-TM antibody as a marker
      for several types of vascular neoplasms vs. previously established endothelial
      markers. METHODS: We examined immunostaining profiles of 30 capillary
      hemangiomas, 10 pyogenic granulomas, five tufted angiomas, 17 Kaposi's sarcomas,
      and nine angiosarcomas. Immunostains for TM, CD34, and vWF were carried out using
      a labeled streptavidin-biotin peroxidase detection system. RESULTS: Anti-TM
      antibody showed moderately intense immunostaining in 89% of benign and malignant
      vascular neoplasms. Anti-CD34 antibody showed moderate to diffuse immunostaining
      in 98% of vascular neoplasms, and vWF showed weak focal staining in 84% of all
      vascular neoplasms examined. CONCLUSION: Anti-TM antibody proved to be a
      sensitive marker for both benign and malignant vascular neoplasms. While not as
      sensitive as anti-CD34, it may have some advantages in specificity that would
      make it a more reliable vascular tumor marker in certain situations.

PMID- 15491325
TI  - Gene expression profiling of porokeratosis demonstrates similarities with
      psoriasis.
AB  - BACKGROUND: Porokeratosis (PK) is a clinically heterogeneous entity associated
      with sharply demarcated, annular, or serpiginous lesions with a hyperkeratotic
      ridge. This disorder is associated with aberrant keratinocyte differentiation
      that histologically manifests as a stack of parakeratin termed the cornoid
      lamella; this structure represents the peripheral hyperkeratotic ridge of
      clinical lesions. Histologically, the keratinocytes forming the cornoid lamella
      demonstrate an altered differentiation program. However, the molecular basis of
      PK remains incompletely understood. METHODS: As a first step in characterizing PK
      at the molecular level, gene expression profiling was performed on a cornoid
      lamella isolated from a large, Mibelli-type porokeratotic lesion. As a control,
      gene expression profiling of peripheral uninvolved epidermis was also performed.
      The gene expression profile of cornoid lamellar keratinocytes was compared with
      similar profiles obtained from a psoriatic plaque and cutaneous squamous cell
      carcinoma. RESULTS: Our study demonstrates a striking similarity between the gene
      expression profiles of PK and psoriasis. In addition, novel markers of the
      porokeratotic keratinocytes were identified, including keratin 16, S-100 A8 and
      A9, and connexin 26. CONCLUSIONS: This study supports the hypothesis that PK is a
      disorder of hyperproliferative keratinocytes exhibiting similarity at the
      molecular level to psoriasis. Consequently, some therapeutic modalities
      efficacious for psoriasis may be of benefit in PK.

PMID- 15491326
TI  - Heat shock protein 27 is expressed in normal and malignant human melanocytes in
      vivo.
AB  - BACKGROUND: Heat shock proteins (HSPs) are a family of highly conserved proteins
      found ubiquitously in mammalian cells, believed to be regulators of normal cell
      physiology and the cellular stress response. In addition, the small 27-kDa heat
      shock protein (HSP27) has previously been found to be a differentiation marker
      for keratinocytes and a prognostic marker associated with increased survival in
      certain cancerous tumors. METHODS: Using immunohistochemistry on routinely
      processed paraffin sections, we examined skin biopsies from 15 invasive
      melanomas, 13 intradermal nevi, and two compound nevi immunostained with a mouse
      monoclonal antibody to HSP27. In addition, cultured melanocytes were heat
      stressed at 45 degrees C for 1 h and then fixed and immunostained in order to
      localize HSP27 expression intracellularly. RESULTS: We found cytoplasmic and
      strong perinuclear staining of HSP27 in melanocytes in normal skin, in melanomas,
      and in nevi. Nuclear reactivity was absent. In addition, in cultured non
      malignant melanocytes, HSP27 expression relocated from the cytoplasm to the
      nucleus with heat stress. CONCLUSIONS: To our knowledge, this investigation is
      the first to demonstrate that HSP27 is expressed in melanocytes in normal skin,
      in nevi, and in non-malignant cultured melanocytes.

PMID- 15491327
TI  - Lymphatic vessel density is significantly increased in melanoma.
AB  - BACKGROUND: Melanoma is well known for its ability to involve regional lymph
      nodes in the early stage. However, the presence of lymphangiogenesis in melanoma
      is still controversial due to lack of lymphatic-specific markers. The purpose of
      this study was to determine the intra- and peritumoral lymphatic vessel density
      (LVD) using a novel lymphatic vessel-specific marker D2-40 and compare it to
      general vessel density (GVD) as determined by CD31 immunostaining in a series of
      melanocytic lesions. METHODS: The intra- and peritumoral GVD and LVD were
      examined by immunohistochemistry using D2-40 and CD31 antibodies in a series of
      melanocytic lesions. RESULTS: We found significantly higher intratumoral LVD in
      melanomas as compared to either common acquired or dysplastic nevi (p < 0.01).
      Although peritumoral LVD in melanoma and malignant melanoma in situ was higher
      compared to nevi, the difference did not reach statistical significance (p =
      0.059). There was no significant difference in GVD among the various groups of
      melanocytic lesions. CONCLUSIONS: Our results show that intratumoral LVD is
      significantly increased in melanomas compared to benign nevi. The higher
      intratumoral lymphatic density in invasive melanomas suggests that melanoma cells
      might promote lymphangiogenesis. In addition, assessment of intratumoral LVD may
      be potentially useful in the differential diagnosis of melanocytic lesions.

PMID- 15491328
TI  - Primary sweat gland carcinosarcoma of the scrotal skin.
AB  - BACKGROUND: Carcinosarcoma is a biphasic tumor composed of malignant epithelial
      and mesenchymal elements. Although the tumors have been reported in different
      locations, they rarely occur in the skin and have not been reported in the skin
      of external genitalia. CASE REPORT: We present such a case in a 71-year-old
      Taiwanese man. He had had a long-term indolent nodule on scrotal skin, but it
      enlarged rapidly in 2 weeks. Wide excision of the tumor was performed. RESULTS
      AND DISCUSSION: The pathologic examination revealed a sweat gland carcinosarcoma
      consisting of admixed mucin-producing adenocarcinoma and solid spindle cell
      sarcoma. The two components exhibited contrasting immunohistochemical profiles
      with the epithelial component diffusely positive for epithelial markers and S-100
      protein, while the sarcomatous component positive for vimentin and smooth muscle
      actin but negative for epithelial markers and S-100 protein. The immunoreactivity
      for S-100 protein in the epithelial component supports sweat gland origin. The
      tumor behaved aggressively. Local recurrence and distant metastases to lungs and
      brain occurred 6 months and 18 months later. The patient died of the disease 20
      months after the initial diagnosis.

PMID- 15491330
TI  - Polymer-based paclitaxel-eluting stents in percutaneous coronary intervention: a
      review of the TAXUS trials.
AB  - Drug-eluting stents have altered the practice of interventional cardiology by
      dramatically reducing the risk of angiographic and clinical restenosis following
      percutaneous coronary intervention. Based on extensive preclinical study and
      clinical trial data, the polymer-based, slow rate-release paclitaxel-eluting
      TAXUS stent has recently received Food and Drug Administration approval for sale
      in the United States. In the current article, we review the available data from
      the TAXUS trials that have demonstrated that implantation of the slow rate
      release TAXUS stent is safe and, in terms of restenosis, markedly superior to
      bare metal stenting for the treatment of de novo lesions <28 mm in length in
      arteries 2.5-3.75 mm in diameter. Additional trials in the TAXUS program are
      currently examining the role of slow and moderate rate-release polymer-based,
      paclitaxel-eluting stents in a broader range of clinical settings and lesion
      subsets.

PMID- 15491331
TI  - The current and future role of percutaneous coronary intervention in patients
      with coronary artery disease.
AB  - With increasing research on vulnerable plaques and uncertainty regarding which
      lesions require revascularization, the goal of this review is to clarify the
      indications for percutaneous coronary intervention and discuss which lesions do
      not warrant treatment by intervention. This paper also briefly reviews the
      potential advantages and limitations of technology that may enable detection of
      atherosclerotic plaques that are prone to rupture and discusses the future
      utility of these technologies in prevention of acute coronary syndromes.
      Providing an evidence-based understanding of lesion morphology and clinical
      variables that influence outcome enables the interventional cardiologist to
      determine which atherosclerotic plaques require PCI.

PMID- 15491332
TI  - Hydrocortisone reduces restenosis after stenting of small coronary arteries.
AB  - Stenting of small coronary arteries has been limited by high rates of restenosis,
      and restenosis after stenting has chiefly been attributed to inflammatory
      reactions resulting in cell proliferation and intimal hyperplasia. In order to
      suppress this inflammatory process, we examined the effects of hydrocortisone, an
      antiinflammatory agent, on restenosis after stenting in a nonrandomized
      retrospective registry. The study population consisted of 193 patients treated at
      two hospitals, who underwent stent implantations in coronary arteries of
      reference diameter <3 mm between February 1999 and September 2001. Target lesions
      included complex, restenotic, diabetic, or chronic total lesions and types of
      implanted stents were Multi-Link, S-series, and gfx stents. Effect of intravenous
      administration of hydrocortisone (200 mg) before stenting was compared to control
      patients who did not receive this treatment. There was no significant difference
      of early outcomes between the hydrocortisone group and the control group. On
      angiographic follow-up at 6 months after stenting, the rate of restenosis was
      significantly lower in patients treated with hydrocortisone as compared with
      control group (22.8% vs 37%, respectively; P < 0.05). The revascularization rate
      of target lesion at 6 months was also significantly lower in the treated group
      (16.5% vs 29%, respectively; P < 0.05). These results suggest that preprocedural
      intravenous administration of hydrocortisone reduces restenosis after stenting of
      small coronary arteries. Prospectively controlled trials will be necessary to
      confirm this preventive effect of hydrocortisone on coronary in-stent restenosis.

PMID- 15491333
TI  - Restenosis after successful ostial stent implantation: the role of statins
      compared with conventional treatment.
AB  - Despite the introduction of coronary stents and effective anticoagulation
      regimens, the treatment of ostial lesions is limited by high restenosis rates.
      Initial results have been published asserting that statin therapy is associated
      with a significant reduction in restenosis after stent deployment. However, no
      information is available about the effect of statins after ostial stenting.
      Between 1993 and 2000, 122 patients required ostial placement of coronary stents
      at the Royal Brompton Hospital in London, United Kingdom. Statin treatment was
      continued or begun in 52 patients with a documentated hypercholesterolemia.
      Follow-up was feasible in 97 patients undergoing successful stent implantation.
      Restenosis rate was lower in patients receiving statins, but did not differ
      significantly from the nonstatin group (34.6% as against 42.2%, P = 0.531).

PMID- 15491334
TI  - Monitoring of enoxaparin level using citrated clotting time during percutaneous
      coronary intervention.
AB  - OBJECTIVES: To evaluate the use of citrated clotting time (CCT) during
      percutaneous coronary intervention (PCI) in both emergent and elective scenarios
      and using intravenous (IV) or subcutaneous (SC) dosing. BACKGROUND: Monitoring of
      enoxaparin during PCI had limitations in the past due to lack of point-of-care
      testing. Introduction of the CCT enables the determination of the degree of
      anticoagulation by enoxaparin. METHODS AND RESULTS: An analysis on 51 consecutive
      patients revealed that after three SC doses (1 mg/kg twice a day) or a single IV
      bolus (1 mg/kg) of enoxaparin, the CCT was consistently in the therapeutic range
      of > or =260 seconds (475 +/- 105 and 565 +/- 151 sec, respectively). Patients
      who received < 3 SC doses of enoxaparin were subtherapeutic for PCI. A
      supplemental IV bolus of 0.3 mg/kg was found always to raise the CCT to
      therapeutic level (499 +/- 178 sec). CONCLUSIONS: Enoxaparin was found to be
      effective and safe during PCI with low vascular complication rate (9.3%).
      Patients who received < 3 SC doses of enoxaparin benefit most from using CCT
      monitoring. IV dosing consistently achieved adequate anticoagulation.

PMID- 15491335
TI  - Same-day discharge after coronary stenting: a feasibility study using a
      hemostatic femoral puncture closure device.
AB  - A major limiting factor for percutaneous coronary interventions carried out via
      the femoral route is the time it takes to achieve femoral artery hemostasis and
      subsequent mobilization. Discharge from hospital usually occurs the following
      day. In this pilot study, we assessed the feasibility of mobilization at 4 hours
      and same-day discharge from hospital of selected elective patients undergoing
      intracoronary stenting using the Angio-Seal Vascular Closure device. Seventy-five
      patients (56 +/- 10 years) with stable single-vessel coronary disease scheduled
      for elective coronary stenting were enrolled. All patients were mobilized at 4
      hours and assessed at 10 hours postprocedure as to their suitability for hospital
      discharge. The first 50 patients remained in hospital overnight. The next 25
      patients followed the same procedures but were discharged at 10 hours. The
      subjects were followed up at 48 hours and 30 days. Hemostasis was achieved in all
      patients following sheath removal and deployment of the Angio-Seal device. Twenty
      patients (27%) had minor groin oozing and two developed small hematoma. There
      were no major bleeding complications, pseudoaneurysm, vascular surgery, or groin
      infection. Groin oozing resulted in the delay of ambulation for 13 subjects but
      discharge was not delayed in any patient. All patients were reported to be
      suitable for hospital discharge at 10 hours postprocedure. There were no further
      complications at 30 days. The present study demonstrated that early mobilization
      and same-day discharge after coronary stenting using the Angio-Seal device is
      feasible in selected patients. Further studies are needed to determine the
      patient selection criteria and the potential cost-saving implications of this
      strategy.

PMID- 15491336
TI  - The EchoMap System: online integration of intracoronary ultrasound and Doppler
      images into angiographic images during cardiac catheterization. Influence on
      radiation exposure and procedure parameters.
AB  - The EchoMap system allows online integration of intravascular ultrasound (IVUS)
      and intracoronary Doppler (ICD) images into angiographic images during
      catheterization, providing exact localization of the IVUS transducer and the ICD
      wire tip position. Although this is a major advance, the use of the system could
      lead to more angiographic documentation sequences and enhanced radiation
      exposure. We investigated the influence of system use on radiation and procedure
      parameters. During a 22-month period, 794 patients underwent coronary angiography
      with simultaneous performance of IVUS and/or ICD. The EchoMap system was applied
      in 392 patients ("EchoMap group"), the remaining 402 patients formed the "No
      EchoMap group." Multivariate regression analysis showed no independent
      association between the use of EchoMap and fluoroscopy time (14.7 +/- 8.5 minutes
      in the EchoMap group vs 14.5 +/- 10 minutes in the No-EchoMap group, P = NS) or
      dose area product (7589 +/- 4916 in the EchoMap group vs 7031 +/- 5434 cGy x
      cm(2), P = NS). EchoMap use was significantly associated with a moderate increase
      in contrast media amount (392 +/- 162 in the EchoMap vs 356 +/- 155 mL in the No
      EchoMap group, P = 0.001). In conclusion, the use of the EchoMap system had no
      significant influence on radiation exposure during cardiac catheterization,
      whereas it was associated with a moderate increase in contrast media amount.

PMID- 15491337
TI  - A novel use of atrial septostomy and stent implantation in a patient with complex
      cyanotic congenital heart disease and severe pulmonary hypertension.
AB  - Patients with unpalliated complex cyanotic congenital heart may have significant
      morbidity resulting from severe pulmonary hypertension. In late stages, medical
      management is often difficult, and worsening right heart failure is resistant to
      medication. The risk of complications and early death can be averted by detailed
      evaluation and prompt intervention to identify the reversible elements that
      compound their physiology. It is vital to address any treatable issue to improve
      a patient's quality of life while awaiting heart-lung transplantation. Our case
      is a good example of such an approach, where the identification and treatment of
      reversible pulmonary venous hypertension in the background of irreversible
      pulmonary arterial hypertension, by offloading the left atrium by atrial
      septostomy and stent implantation, resulted in significant improvement in the
      quality of life for the patient.

PMID- 15491338
TI  - The influence of obstructive sleep apnea on FFR measurements for coronary lesion
      assessment.
AB  - Fractional flow reserve (FFR) determinations have been demonstrated to be largely
      independent of changes in systemic hemodynamic changes. Herein, we describe a
      case of obstructive sleep apnea cyclically altering FFR measurements from normal
      to abnormal in a patient with an intermediately severe coronary narrowing
      following treatment for an acute coronary syndrome. To eliminate uncertainty, FFR
      measurements should be made if possible during suspended respiration.

PMID- 15491339
TI  - Approach to the patient with prior bypass surgery.

PMID- 15491340
TI  - Use of water 'softening and conditioning systems' significantly increases the
      risk of periodontitis: smoking considerations.
AB  - BACKGROUND: The role of water in the etiology of periodontal disease is poorly
      understood. OBJECTIVES: The objective of this study was to examine the
      association amongst water softness, risk for periodontitis, and smoking status.
      METHODS: We examined the association between use of water 'softening and
      conditioning systems' and the risk for periodontal disease in smokers and non
      smokers, using adult participants (18+ years), from the third National Health and
      Nutrition Examination Survey (NHANES III) data. Zero to 33 per cent (0-33%) of
      sites with periodontal attachment loss > or = 3 mm was considered a healthy
      periodontium, and > 33% of sites with periodontal attachment loss > or = 3 mm was
      defined as periodontitis. Soft water users were divided into 'yes' or 'no' using
      the question, 'Does your home have a "softening or conditioning system?".'
      Smoking subjects were divided into groups as follows: current smokers (had smoked
      > or = 100 cigarettes in their lifetime and currently smoked), former smokers
      (had smoked > or = 100 cigarettes in their lifetime, not currently smoking), or
      never smokers (had not smoked > or = 100 cigarettes in their lifetime). Data was
      analyzed by univariate analyses using SPSS. The 5% level of statistical
      significance was adopted throughout. RESULTS: Subjects that answered the question
      'yes' to soft water use had a significantly higher risk of periodontitis (p <
      0.05), adjusting for confounders. When mineral intake from foods was added to the
      model, the significance of periodontitis risk remained the same for the non
      smoking, soft water-using subjects, whereas for the smoking, soft water-using
      subjects the risk for periodontitis increased significantly (p < 0.05) in most
      cases. CONCLUSIONS: Thus, use of water 'softening and conditioning systems'
      significantly increased the risk for periodontitis, and smoking increased this
      risk.

PMID- 15491341
TI  - Behavior of human periodontal ligament cells on CO2 laser irradiated dentinal
      root surfaces: an in vitro study.
AB  - OBJECTIVE: The aim of this study was to investigate the in vitro attachment
      behavior of human periodontal ligament fibroblasts on periodontally involved root
      surface after conditioning with CO2 laser and to compare its efficacy with
      chemical conditioning agents, namely tetracycline hydrochloride, citric acid,
      hydrogen peroxide (H2O2) and EDTA, using scanning electron microscopy. METHODS: A
      total of 84 scaled and root-planed specimens from periodontally involved single
      rooted human teeth showing hopeless prognosis were selected and assigned to two
      groups. One group was lased with a CO2 laser (from 5 cm at 3 W for 0.8, 1.0 and
      1.2 s), and the other group was treated with either tetracycline hydrochloride
      (2.5%), citric acid (saturated solution, pH 1), H2O2 (6%) or EDTA (5%; pH 7.4)
      for 3 min. The specimens were then seeded with human periodontal ligament
      fibroblasts, incubated for either 12 h or 24 h, and then the cell attachment
      behavior was observed. RESULTS: CO2 laser irradiation for 1.0 s was found to be
      the most efficient, showing consistently good cell attachment with the highest
      mean value (15.00 +/- 3.41 cells/10,000 microm2 after incubation for 12 h and
      29.17 +/- 2.04 cells/10,000 microm2 after 24 h), followed by irradiation for 0.8
      s (13.11 +/- 3.04 cells/10,000 microm2 after incubation for 12 h and 22.91 +/-
      7.10 cells/10,000 microm2 after 24 h). Charring was observed following
      irradiation for 1.2 s. Amongst chemical conditioning agents, citric acid was
      found to be the most efficient, with a mean cell attachment of 17.82 +/- 2.16
      cells/10,000 microm2 after incubation for 12 h and 23.62 +/- 1.94 cells/10,000
      microm2 after 24 h. EDTA and H2O2 did not do well in the study. CONCLUSION: The
      results suggest that CO2 laser irradiation for 1.0 s may promote comparatively
      better attachment of periodontal ligament fibroblast on dentinal root surfaces
      than the conventional chemical conditioning agents used in the study.

PMID- 15491342
TI  - Epidermal growth factor stimulates urokinase-type plasminogen activator
      expression in human gingival fibroblasts. Possible modulation by genistein and
      curcumin.
AB  - BACKGROUND: Regulation of the extracellular matrix turnover is a crucial process
      in wound healing and the progress of periodontal disease. It has been proposed
      that urokinase-type plasminogen activator (uPA), under the control of growth
      factors or cytokines, provides the proteolytic potential to the accomplishment of
      these cellular events. Epidermal growth factor (EGF) is one of the growth factors
      that has been shown to be active in uPA regulation. METHODS: In this study, we
      have assessed the effect of EGF on uPA expression in primary cultures of human
      gingival fibroblasts. We also studied the signaling pathways involved in this
      process and the role of the dietary phytoestrogens curcumin and genistein as
      potential modulators of this response. RESULTS: Human gingival fibroblasts
      expressed a basal uPA activity, which was inhibited by genistein, but not by
      curcumin. After treatment with 10 ng/ml EGF, uPA production was strongly
      stimulated. Exposure to genistein and curcumin inhibited EGF-stimulated urokinase
      production, although only genistein showed a statistically significant inhibitory
      response. Using more specific inhibitors, we found that the mitogen-activated
      extracellular kinase and c-Jun N-terminal kinase (JNK) inhibitors PD98059 and
      SP600125 also blocked the EGF-dependent stimulatory effect. On the other hand,
      SB203580, inhibitor of the p38 member of mitogen-activated protein kinase family,
      did not alter this response. In accordance to these findings, EGF stimulated a
      potent activation of JNK and a mild activation of extracellular signal-regulated
      kinases 1/2. Finally, EGF stimulated the phosphorylation of its receptor and
      tyrphostin (AG1478), curcumin and genistein were able to inhibit this stimulatory
      effect. CONCLUSIONS: These results indicate that EGF constitutes a strong stimuli
      on uPA expression in human gingival fibroblasts. Our data also shows that EGF
      stimulated uPA production involves the activation of the extracellular signal
      regulated kinases 1/2 and JNK signaling pathways and might be modulated by the
      natural phytoestrogens curcumin and genistein.

PMID- 15491343
TI  - The involvement of platelet-derived growth factor receptors and insulin-like
      growth factor-I receptors signaling during mineralized nodule formation by human
      periodontal ligament cells.
AB  - BACKGROUND AND OBJECTIVE: Periodontal ligament cells are regarded to have the
      capacity to differentiate into cementoblasts or osteoblasts, and are capable of
      forming a mineralized nodule in vitro. However, the precise mechanisms are
      unclear. Here we evaluated the possible involvement of growth factor receptors,
      such as the platelet-derived growth factor receptor (PDGFR), insulin-like growth
      factor-I receptor (IGF-IR), and epidermal growth factor receptor (EGFR) on
      periodontal ligament cells and their ligands during periodontal ligament cells
      differentiation in vitro. METHODS: Human periodontal ligament cells were
      differentiated via culturing in the presence of dexamethasone, ascorbic acid, and
      beta-glycerophosphate for mineralized nodule formation, characterized by von
      Kossa staining. Expressions of receptors and their ligands were analyzed by flow
      cytometry/reverse transcription-polymerase chain reaction. RESULTS: During the
      differentiation, PDGFR-alpha was held at a lower level compared with the control.
      PDGFR-beta, however, was maintained at a slightly higher level that was reversed
      to the control level when mineralized nodules formed. In contrast, IGF-IR and
      EGFR were not substantially different from the control. The mineralized nodule
      formation was strongly inhibited by a PDGFR kinase blocker (AG1295 and AG1296),
      partially inhibited by an IGF-IR kinase blocker (I-Ome-AG538 and AG1024), and not
      inhibited by an EGFR kinase blocker (AG99). PDGF-A, PDGF-C, PDGF-D, IGF-I, and
      IGF-II, but not PDGF-B, were expressed on the control as well as
      dexamethasone/ascorbic acid-treated periodontal ligament cells during mineralized
      nodule formation; however, the pattern of their expressions was quite different.
      CONCLUSION: These findings suggest that a pathway of PDGFs/PDGFR and IGFs/IGF-IR
      on periodontal ligament cells are involved during mineralized nodule formation,
      and that PDGFs and IGFs expressed by periodontal ligament cells may contribute to
      the formation.

PMID- 15491344
TI  - The distribution of periodontopathic bacteria among Japanese children and their
      parents.
AB  - OBJECTIVE AND BACKGROUND: It is not well known how periodontopathic bacteria
      colonize in the oral cavity during childhood. The purpose of this study was to
      investigate the distribution of periodontopathic bacteria in oral cavities of
      children and their parents and the relationship between the bacterial findings
      and clinical parameters. METHODS: Fifty-six children (mean age: 8.3 +/- 3.5,
      range: 1-15 years), including 15 with deciduous dentition, 26 with mixed
      dentition and 15 with permanent dentition, and their parents participated in this
      study. Whole saliva and dental plaque of the children and whole saliva of their
      parents were collected for detection of seven species of periodontopathic
      bacteria (Actinobacillus actinomycetemcomitans, Tannerella forsythensis
      (Bacteroides forsythus), Campylobacter rectus, Porphyromonas gingivalis,
      Prevotella intermedia, Prevotella nigrescens and Treponema denticola) using the
      polymerase chain reaction method. Clinical parameters including simplified Oral
      Hygiene Index and Papillary-Marginal-Attachment Index were recorded for the
      children and their accompanied parents. RESULTS: The detection frequencies of T.
      forsythensis, C. rectus, P. nigrescens, T. denticola, A. actinomycetemcomitans
      and P. gingivalis in the oral cavities of children were 42.9%, 94.6%, 42.9%,
      48.2%, 1.8% and 8.9%, respectively. T. forsythensis, P. gingivalis and T.
      denticola were detected more frequently in the saliva of parents (54.8%, 54.8%,
      88.1%, respectively) than in the saliva of children (25.5%, 7.3%, 41.8%,
      respectively). Different detection frequencies of P. nigrescens were found among
      the oral cavities of children with deciduous, mixed and permanent dentitions. In
      mixed dentition, females harbored T. forsythensis more frequently than males did.
      Children who harbored T. forsythensis, P. intermedia, P. nigrescens and T.
      denticola showed high scores for oral debris measurement by simplified Oral
      Hygiene Index. T. forsythensis, P. intermedia and P. nigrescens were detected
      more frequently in children whose parents were positive for these pathogens than
      in children whose parents were negative. CONCLUSIONS: High plaque retention seems
      to promote the colonization of periodontal pathogens in the oral cavities of
      children. T. forsythensis, P. intermedia and P. nigrescens were detected more
      frequently in the oral cavities of children whose parents already harbored these
      bacteria. Familial transmission of these bacteria is suggested.

PMID- 15491345
TI  - Effects of alendronate on restoration of biomechanical properties of periodontium
      in replanted rat molars.
AB  - OBJECTIVE: We examined the effect of the pretreatment of roots with alendronate
      on the restoration of the support function of the healing periodontal ligament in
      replanted rat molars. METHODS: The left maxillary first molars were extracted,
      placed in 0.9% NaCl containing 1 mm alendronate (alendronate group) or 0.9% NaCl
      (control group) for 5 min, and were replanted into their sockets. Groups of
      animals were killed at 7, 14, and 21 days after replantation. Normal control rats
      were also killed on the same days. The force required to extract the replanted or
      normal tooth from its socket was measured, and a load-deformation curve was
      developed and analyzed. Micro-computed tomography and histologic analyses were
      also made. RESULTS: The mechanical properties of the healing periodontal ligament
      in the alendronate group were gradually restored from 7 to 21 days. However,
      fractures of the roots and bones during mechanical testing occurred in most of
      the replanted teeth in the control group at 21 days. The rates of restoration of
      the mechanical strength, extensibility, stiffness, and toughness for the
      alendronate group at 21 days were 67, 98, 74, and 68% of the normal controls,
      respectively. Micro-computed tomography and histologic observations revealed that
      bone-like structures within the pulp and ankylosis between the roots and socket
      bones occurred commonly in the control group, but were uncommon in the
      alendronate group. CONCLUSIONS: Our findings suggest that the pretreatment with
      alendronate inhibits the formation of abnormal mineralized tissues and results in
      better restoration of the support function of the healing periodontal ligament in
      replanted teeth.

PMID- 15491346
TI  - Pre-exposure to high glucose augments lipopolysaccharide-stimulated matrix
      metalloproteinase-1 expression by human U937 histiocytes.
AB  - BACKGROUND AND OBJECTIVES: It has been well established that patients with
      diabetes have increased prevalence and severity of periodontal diseases. However,
      the underlying mechanisms are not well understood. Given that bacterial infection
      is the primary cause of periodontal disease, we postulated that hyperglycemia may
      interplay with bacterial virulence factors such as lipopolysaccharide to up
      regulate matrix metalloproteinase (MMP), leading to increased periodontal tissue
      destruction. METHODS AND RESULTS: We showed that prolonged pre-exposure of U937
      histiocytes to high glucose markedly increased lipopolysaccharide-stimulated MMP
      1 secretion and mRNA expression. Our results also showed that the effect of high
      glucose on lipopolysaccharide-induced MMP-1 expression is cell type-specific
      because no similar response was observed in human gingival fibroblasts. In
      addition to MMP-1, high glucose also augments lipopolysaccharide-stimulated MMP
      7, -8, and -9 mRNA expression. In the investigation of the signaling pathways
      involved in the enhancement of lipopolysaccharide-induced MMP-1 expression by
      high glucose, we found that both high glucose and lipopolysaccharide regulate MMP
      1 expression through the nuclear factor kappaB (NFkappaB) and mitogen-activated
      protein kinase (MAPK) cascades. CONCLUSIONS: The present study has shown that pre
      exposure to high glucose and subsequent lipopolysaccharide treatment
      synergistically stimulates MMP-1 expression by mononuclear phagocytes through the
      NFkappaB and MAPK signaling pathways. This study has thus delineated a pathogenic
      mechanism that may be involved in the exacerbated periodontal disease in diabetic
      patients.

PMID- 15491347
TI  - Prevotella intermedia lipopolysaccharide stimulates release of nitric oxide by
      inducing expression of inducible nitric oxide synthase.
AB  - OBJECTIVES: The purpose of this study was to examine the effects of
      lipopolysaccharide from Prevotella intermedia, a major cause of inflammatory
      periodontal disease, on the production of nitric oxide (NO) and expression of
      inducible nitric oxide synthase (iNOS) in the murine macrophage cell line
      RAW264.7. We also attempted to throw light on the signaling mechanisms involved
      in P. intermedia lipopolysaccharide-induced NO production. MATERIAL AND METHODS:
      Lipopolysaccharide from P. intermedia ATCC 25611 was prepared by the standard hot
      phenol-water method. NO production was assayed by measuring the accumulation of
      nitrite in culture supernatants. Western blot analysis of iNOS and analysis of
      reverse transcription-polymerase chain reaction (RT-PCR) products were carried
      out. RESULTS: We found that P. intermedia lipopolysaccharide can induce iNOS
      expression and stimulate the release of NO without additional stimuli and
      demonstrated an important role of the transcription factor nuclear factor-kappaB
      (NF-kappaB) and microtubule polymerization in NO production. The production of NO
      required l-arginine but not activation of protein kinase C or protein tyrosine
      kinase. CONCLUSIONS: The present study clearly shows that P. intermedia
      lipopolysaccharide fully induced iNOS expression and NO production in RAW264.7
      cells in the absence of other stimuli. The ability of P. intermedia
      lipopolysaccharide to promote the production of NO may be important in the
      pathogenesis of inflammatory periodontal disease.

PMID- 15491348
TI  - The interleukin-10 knockout mouse is highly susceptible to Porphyromonas
      gingivalis-induced alveolar bone loss.
AB  - OBJECTIVE: Interleukin-10 is an anti-inflammatory cytokine that reduces
      periapical bone loss, but its role in periodontal bone loss is unclear. In the
      present study, we tested the hypothesis that endogenous interleukin-10 is a
      potent suppressor of Porphyromonas gingivalis-induced alveolar bone loss in vivo.
      METHODS: Interleukin-10 knockout (-/-) and wild-type mice were inoculated
      intraorally with P. gingivalis. Non-infected animals served as negative controls.
      Alveolar bone loss, gingival cytokine levels, and gingival gene expression were
      assessed using morphometric analysis, enzyme-linked immunosorbent assay (ELISA),
      and semiquantitative reverse transcription polymerase chain reaction (RT-PCR),
      respectively. RESULTS: P. gingivalis-infected interleukin-10(-/-) mice exhibited
      severe alveolar bone loss compared to non-infected interleukin-10(-/-) and wild
      type mice by day 42. Surprisingly, bone resorptive cytokines interleukin-1alpha
      and tumor necrosis factor alpha (TNF-alpha) were not up-regulated in gingival
      tissues by P. gingivalis-infection. Although interleukin-1beta was marginally
      increased, blockade of both interleukin-1 isoforms or interleukin-1 receptor type
      I with neutralizing antisera failed to reduce alveolar bone loss in interleukin
      10(-/-) mice, indicating the operation of an interleukin-1-independent mechanism.
      No strong correlations between bone loss and other cytokines was observed,
      although interferon gamma (IFNgamma), interleukin-6, interleukin-4, and
      prostaglandin E2 were modestly up-regulated in infected interleukin-10(-/-) mice.
      P. gingivalis infection reduced the expression of cell markers in gingival tissue
      on days 7 and 14 in both interleukin-10(-/-) and wild-type animals, suggestive of
      bacteria-induced cytotoxicity or apoptosis. This was followed by up-regulated
      expression of receptor activator of nuclear factor kappa B ligand (RANKL) and
      CD40 ligand (CD40L on days 28 and 70 in infected interleukin-10(-/-) mice only.
      CONCLUSION: The interleukin-10(-/-) mouse is highly susceptible to bone loss
      induced by the periodontal pathogen P. gingivalis, which is mediated via an
      interleukin-1-independent pathway.

PMID- 15491350
TI  - Factor XIIIa+ dendritic cells and S-100 protein+ Langerhans' cells in adult
      periodontitis.
AB  - OBJECTIVE: The purpose of this study was to evaluate the presence of factor
      XIIIa+ dendritic cells and S-100 protein+ Langerhans' cells in the gingival
      epithelium and connective tissue of periodontal pockets, before and after non
      surgical periodontal therapy. BACKGROUND: The microbial flora in periodontal
      pockets provokes complex immune reactions. Dendritic cells play a critical role
      in primary and secondary immune responses and are considered as antigen
      presenting cells. Factor XIIIa positive dendritic cells and S-100 protein
      positive Langerhans' cells identified by immunoreactivity against factor XIIIa
      antigen and S-100 protein, respectively, are two distinct subpopulations of
      dendritic cells. METHODS: Fifty-four gingival tissue samples were obtained from
      periodontal pockets of initial depth 4-5 mm and > or = 6 mm. Each group was
      subdivided in to three subgroups. The first subgroup consisted of samples taken
      on baseline day and used as control. The second and third subgroups included
      those obtained 1 month after plaque and calculus removal, and 1 month after
      scaling and root planing, respectively, additionally to oral hygiene
      instructions. The tissues were removed from the palatal gingiva under local
      anaesthesia during routine periodontal surgery. Immunohistochemical staining with
      antibodies against factor XIIIa and S-100 protein was performed to identify
      dendritic cells positive and Langerhans' cells positive, respectively. RESULTS:
      Factor XIIIa+ dendritic cell numbers decreased compared to controls after plaque
      and calculus removal, oral hygiene instructions and scaling and root planing in
      periodontal pockets of 4-5 mm, but not in those of > or = 6 mm depth. S-100+
      Langerhans' cell numbers decreased after periodontal treatment in the periodontal
      pockets > or = 6 mm. CONCLUSION: These results may reflect a tendency for
      reduction of these two distinctive subpopulations of dendritic cells after non
      surgical periodontal therapy.

PMID- 15491349
TI  - Periodontal pathogens in atheromatous plaques. A controlled clinical and
      laboratory trial.
AB  - OBJECTIVE: A possible relationship between periodontitis and cardiovascular
      disease has been suggested. The aims of this controlled clinical study were: (i)
      to ascertain the presence of periodontal bacteria DNA [Actinobacillus
      actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas gingivalis,
      Prevotella intermedia, Tannerella forsythensis (formerly Bacteroides forsythus)]
      in carotid atheromatous plaques and (ii) to assess the concomitant presence of
      the same periodontal bacteria DNA, if any, in periodontal pockets and in carotid
      atheroma in the same patient. METHODS: A total of 52 patients scheduled for
      carotid endarderectomy were enrolled in this study. The test group consisted of
      26 dentate patients; the control group included 26 edentulous patients. A
      complete periodontal examination, including radiographic orthopanoramic and
      subgingival plaque sample, was performed in the test population. Oral and X-ray
      examinations were performed in the control group. Atheromatous plaques were
      harvested during surgical procedure for each dentate and edentulous patient and
      then sent to the microbiological laboratory. Subgingival plaque samples and
      carotid specimens were examined using the polymerase chain reaction (PCR)
      technique by means of specific primers for periodontal bacteria. Amplification of
      extracted DNA was tested using human beta-globin specific-primers. RESULTS: Out
      of 52 endarterectomy samples, 12 (seven dentate, five edentulous patients) were
      excluded as negative to DNA amplification. In subgingival plaque samples of 19
      test patients, T. forsythensis (79%), F. nucleatum (63%), P. intermedia (53%), P.
      gingivalis (37%) and A. actinomycetemcomitans (5%) were found. No periodontal
      bacteria DNA was detected by PCR in any of the carotid samples in either patient
      group. CONCLUSION: The presence of periodontal bacteria DNA in atheromatous
      plaques could not be confirmed by this study and thus no correlation could be
      established between species associated with periodontal disease and putative
      bacteria contributing to atheromatous plaques.

PMID- 15491351
TI  - Molecular approaches to malaria.
AB  - Malaria is a serious health problem in developing countries. With the complete
      sequencing of the genomes of the parasite and of the mosquito vector, malaria
      research has entered the post-genome era. In this report we summarize the results
      and new research avenues presented at a recent meeting held with the aim of
      developing interdisciplinary approaches to combat this disease.

PMID- 15491352
TI  - Bacterial cell division and the septal ring.
AB  - Cell division in bacteria is mediated by the septal ring, a collection of about a
      dozen (known) proteins that localize to the division site, where they direct
      assembly of the division septum. The foundation of the septal ring is a polymer
      of the tubulin-like protein FtsZ. Recently, experiments using fluorescence
      recovery after photobleaching have revealed that the Z ring is extremely dynamic.
      FtsZ subunits exchange in and out of the ring on a time scale of seconds even
      while the overall morphology of the ring appears static. These findings, together
      with in vitro studies of purified FtsZ, suggest that the rate-limiting step in
      turnover of FtsZ polymers is GTP hydrolysis. Another component of the septal
      ring, FtsK, is involved in coordinating chromosome segregation with cell
      division. Recent studies have revealed that FtsK is a DNA translocase that
      facilitates decatenation of sister chromosomes by TopIV and resolution of
      chromosome dimers by the XerCD recombinase. Finally, two murein hydrolases, AmiC
      and EnvC, have been shown to localize to the septal ring of Escherichia coli,
      where they play an important role in separation of daughter cells.

PMID- 15491353
TI  - Why is transcription coupled to translation in bacteria?
AB  - Active mechanisms exist to prevent transcription that is uncoupled from
      translation in the protein-coding genes of bacteria, as exemplified by the
      phenomenon of nonsense polarity. Bacterial transcription-translation coupling may
      be viewed as one among several co-transcriptional processes, including those for
      mRNA processing and export in the eukaryotes, that operate in the various life
      forms to render the nascent transcript unavailable for formation of otherwise
      deleterious R-loops in the genome.

PMID- 15491354
TI  - SsaM and SpiC interact and regulate secretion of Salmonella pathogenicity island
      2 type III secretion system effectors and translocators.
AB  - The type III secretion system (TTSS) encoded by Salmonella Pathogenicity Island 2
      (SPI-2) is required for systemic infection and intracellular replication of
      Salmonella enterica serovar Typhimurium. The SPI-2 TTSS is activated after
      internalization of bacteria by host cells, and translocates effector proteins
      into and across the vacuolar membrane, where they interfere with several host
      cell functions. Here, we investigated the function of SsaM, a small protein
      encoded within SPI-2. An ssaM deletion mutant had virulence and intracellular
      replication defects comparable to those of a SPI-2 TTSS null mutant. Although the
      ssaM mutant was able to secrete the effector protein SseJ in vitro, it failed to
      translocate SseJ into host cells, and to secrete the translocon proteins SseB,
      SseC and SseD in vitro. This phenotype is similar to that of a strain carrying a
      mutation in the SPI-2 gene spiC, whose product is reported to be an effector
      involved in trafficking of the Salmonella vacuole in macrophages. Both ssaM and
      spiC mutants were found to oversecrete the SPI-2 effector proteins SseJ and PipB
      in vitro. Fractionation assays and immunofluorescence microscopy were used to
      investigate the localization of SsaM and SpiC in macrophages. No evidence for
      translocation of these proteins was obtained. The similar phenotypes of the ssaM
      and spiC mutants suggested that they might be involved in the same function. Pull
      down and co-immune precipitation experiments showed that SpiC and SsaM interact
      within the bacterial cell. We propose that a complex involving SsaM and SpiC
      distinguishes between translocators and effector proteins, and controls their
      ordered secretion through the SPI-2 TTSS.

PMID- 15491355
TI  - Genetic evidence for functional interactions between TolC and AcrA proteins of a
      major antibiotic efflux pump of Escherichia coli.
AB  - Genetic data have suggested that TolC, AcrA and AcrB constitute a major
      antibiotic efflux system in Escherichia coli. Through reversion analysis of an
      unstable and antibiotic-sensitive TolC mutant (TolCP246R,S350C), we isolated
      extragenic suppressors that mapped within the acrRAB loci. DNA sequence analysis
      revealed that 18 isolates contained 10 different missense mutations within the
      acrA gene, whereas a single isolate had a missense mutation within the acrR gene,
      which codes for the acrAB repressor. Besides reversing the hypersensitivity
      phenotype of TolCP246R,S350C, AcrA and AcrR alterations elevated the mutant TolC
      protein level, thus indicating that the mechanism of suppression involves the
      stabilization of an unstable mutant TolC protein. Eight of the 10 AcrA
      alterations were clustered in the 202-265 region of the mature protein, whereas
      the other two suppressors affected residues 30 and 146. Based on the recently
      solved crystal structure of MexA, an AcrA counterpart from Pseudomonas
      aeruginosa, the regions encompassing residues 30 and 202-265 constitute the
      alpha+beta-domain of AcrA (MexA), whereas that of 146 form the alpha-domain. The
      data suggest that residues of these two AcrA domains either directly or
      indirectly influence interactions with TolC. Curiously, the stability of three
      mutant AcrA proteins, bearing an L222Q, L222R or P265R substitution, became
      dependent on the presence of either wild-type or mutant TolC. This dependence of
      the mutant AcrA proteins on TolC further supported the notion of a direct
      physical interaction between these two proteins. Because a mutation in acrR or
      acrAB expression from a multicopy plasmid also suppressed the TolCP246R,S350C
      defects, it indicated that wild-type AcrA when produced in high levels presumably
      establishes similar interactions with the mutant TolC protein as do the
      suppressor forms of AcrA produced from the chromosomal copy. The AcrA-mediated
      suppression of mutant TolC phenotypes and the stabilization of mutant TolC
      protein were dependent on AcrB, reflecting the existence of a functional complex
      between TolC and AcrAB in vivo.

PMID- 15491356
TI  - Characterization of an ABCA-like transporter involved in vesicular trafficking in
      the protozoan parasite Trypanosoma cruzi.
AB  - Protozoan parasites are responsible of important healthy problems, among others
      malaria, leishmaniasis and trypanosomiasis. The present work reports the
      characterization of the first mammalian ATP-binding cassette transporter,
      subfamily A (ABCA)-like in Trypanosoma cruzi. TcABC1 is a single copy gene
      differentially expressed along the life cycle of the parasite, being absent in
      its infective form. TcABC1 localizes to the plasma membrane, flagellar pocket and
      intracellular vesicles. Functional studies of TcABC1 in transfected parasites
      suggest that the protein is implicated in intracellular trafficking, as
      determined by the analysis of endocytosis and exocytosis events. The accumulation
      of the endocytic markers FM4-64 and NBD-SM is increased in transfected parasites.
      Similarly, ectophosphatase and ectoATPase activities are increased in TcABC1
      overproducers. Indeed, transmission electronic microscopy analysis showed a
      higher number of intracellular vesicles in TcABC1 transfectants. Taken together,
      these results suggest that the protein is involved in the endocytic and exocytic
      pathways of T. cruzi.

PMID- 15491357
TI  - Structure and assembly of the pseudopilin PulG.
AB  - The pseudopilin PulG is one of several essential components of the type II
      pullulanase secretion machinery (the Pul secreton) of the Gram-negative bacterium
      Klebsiella oxytoca. The sequence of the N-terminal 25 amino acids of the PulG
      precursor is hydrophobic and very similar to the corresponding region of type IV
      pilins. The structure of a truncated PulG (lacking the homologous region), as
      determined by X-ray crystallography, was found to include part of the long N
      terminal alpha-helix and the four internal anti-parallel beta-strands that
      characterize type IV pilins, but PulG lacks the highly variable loop region with
      a disulphide bond that is found in the latter. When overproduced, PulG forms
      flexible pili whose structural features, as visualized by electron microscopy,
      are similar to those of bacterial type IV pili. The average helical repeat
      comprises 17 PulG subunits and four helical turns. Electron microscopy and
      molecular modelling show that PulG probably assembles into left-handed helical
      pili with the long N-terminal alpha-helix tightly packed in the centre of the
      pilus. As in the type IV pilins, the hydrophobic N-terminal part of the PulG
      alpha-helix is necessary for its assembly. Subtle sequence variations within this
      highly conserved segment seem to determine whether or not a type IV pilin can be
      assembled into pili by the Pul secreton.

PMID- 15491358
TI  - Intestinal barrier dysfunction by enteropathogenic Escherichia coli is mediated
      by two effector molecules and a bacterial surface protein.
AB  - The human intestinal pathogen, enteropathogenic Escherichia coli (EPEC), causes
      diarrhoeal disease by a mechanism that is dependent on the injection of effector
      proteins into the host cell. One effector, EspF, is reported to be required for
      EPEC to disrupt tight junction integrity of intestinal cells and increase the
      paracellular movement of molecules, which is likely to contribute to diarrhoea.
      Here, we show that not one but three EPEC-encoded factors play important roles in
      this process. Thus, the Map (Mitochondria-associated protein) effector is shown
      to: (i) be as essential as EspF for disrupting intestinal barrier function, (ii)
      be able to function independently of EspF, (iii) alter tight junction structure
      and (iv) mediate these effects in the absence of mitochondrial targeting.
      Additionally, the outer membrane protein Intimin is shown to be crucial for EspF
      and Map to disrupt the intestinal barrier function. This function of Intimin is
      completely independent of its interaction with its known receptor Tir, revealing
      a physiologically relevant requirement for Intimin interaction with alternative
      receptor(s). This work demonstrates that EPEC uses multiple multifunctional
      proteins to elicit specific responses in intestinal cells and that EPEC can
      control the activity of its injected effector molecules from its extracellular
      location.

PMID- 15491359
TI  - Export of Plasmodium falciparum calcium-dependent protein kinase 1 to the
      parasitophorous vacuole is dependent on three N-terminal membrane anchor motifs.
AB  - Calcium-dependent protein kinases play a pivotal role in calcium signalling in
      plants and some protozoa, including the malaria parasites. They are found in
      various subcellular locations, suggesting an involvement in multiple signal
      transduction pathways. Recently, Plasmodium falciparum calcium-dependent protein
      kinase 1 (PfCDPK1) has been found in the membrane and organelle fraction of the
      parasite. The kinase contains three motifs for membrane binding at its N
      terminus, a consensus sequence for myristoylation, a putative palmitoylation site
      and a basic motif. Endogenous PfCDPK1 and the in vitro translated kinase were
      both shown to be myristoylated. The supposed membrane attachment function of the
      basic cluster was experimentally verified and shown to participate together with
      N-myristoylation in membrane anchoring of the kinase. Using immunogold electron
      microscopy, the protein was detected in the parasitophorous vacuole and the
      tubovesicular system of the parasite. Mutagenesis of the predicted acylated
      residues and the basic motif confirmed that dual acylation and the basic cluster
      are required for correct targeting of Aequorea victoria green fluorescent protein
      to the parasitophorous vacuole, suggesting that PfCDPK1 as the leishmanial
      hydrophilic acylated surface protein B is a representative of a novel class of
      proteins whose export is dependent on a 'non-classical' pathway involving N
      myristoylation/palmitoylation.

PMID- 15491360
TI  - Axiom of determining transcription start points by RNA polymerase in Escherichia
      coli.
AB  - To investigate the determining factors in the selection of the transcription
      start points (tsp) by RNA polymerase of Escherichia coli, we systematically
      deleted or substituted single base pairs (bps) at 25 putative critical positions
      in the two extended -10 promoters, P1 and P2, of the gal operon. These changes
      extend downstream from -24 to +1 of the P1 promoter. In vitro transcription
      assays using supercoiled DNA templates revealed a preference for a purine in the
      non-template strand for tsp in both promoters. The optimal tsp is the 11th bp
      counting downstream from the -10 position. A single bp deletion anywhere from -10
      to +1 switched the tsp to the next available purine 2-3 bp downstream on the non
      template strand whereas deleting a single bp at position from -24 to -11 did not
      affect the tsp. The nature of the 10 bp sequence of the -10 to -1 region, while
      affecting promoter strength, did not influence tsp. The cAMP-CRP complex, which
      stimulates P1 and represses P2, did not affect the tsp selection process. The
      rules of tsp selection by RNA polymerase containing sigma70 in gal and pyr
      promoters discussed here may be applicable to others.

PMID- 15491361
TI  - Metabolic differentiation in actively swarming Salmonella.
AB  - Most current paradigms of microbial metabolism have been derived from studying
      cells grown under a variety of nutrient compositions in aqueous environments.
      With recent advances in genomics and experimental techniques, alternative forms
      of bacterial growth are increasingly being explored. When propagated on nutrient
      rich semi-solid media, several species of bacteria undergo a morphological
      differentiation into swarmers that are capable of migrating on surfaces. Recent
      studies indicate that swarmer differentiation represents much more than a
      motility phenotype, as several clinically important attributes are also co
      regulated. We demonstrate that migrating swarmer cells of Salmonella are
      metabolically differentiated compared to the vegetative swimmer cells grown in
      the same nutrient environment. Furthermore, once the cells have differentiated,
      the swarmers remain in this physiological state under conditions that do not
      promote the initial differentiation. The bacterium's capacity to override some of
      the classic paradigms of metabolic regulation established in aqueous environments
      represents a unique physiological response by the pathogen that may be
      advantageous in polymicrobial environments such as the host.

PMID- 15491362
TI  - Regulation of FlbD activity by flagellum assembly is accomplished through direct
      interaction with the trans-acting factor, FliX.
AB  - The temporal and spatial transcription of late flagellar genes in Caulobacter
      crescentus is regulated by the sigma54 transcriptional activator, FlbD. One
      requirement for FlbD activity is the assembly of a structure encoded by early,
      class II flagellar genes. In this report, we show that the trans-acting factor
      FliX predominantly functions as a negative regulator of FlbD activity in the
      absence of the class II-encoded flagellar structure. In contrast, a mutant FliX
      that bypasses the transcriptional requirement for early flagellar assembly is
      incapable of repressing FlbD in a class II flagellar mutant. Expression of this
      mutant allele, fliX1, does not alter the temporal pattern of FlbD-dependent
      transcription. Remarkably, this mutation confers the correct cell cycle timing of
      hook operon transcription in a strain that cannot assemble the flagellum,
      indicating that the progression of flagellar assembly is a minor influence on
      temporal gene expression. Using a two-hybrid assay, we present evidence that FliX
      regulates FlbD through a direct interaction, a novel mechanism for this class of
      sigma54 transcriptional activator. Furthermore, increasing the cellular levels of
      FliX results in an increase in the concentration of FlbD, and a corresponding
      increase in FlbD-activated transcription, suggesting that FliX and FlbD form a
      stable complex in Caulobacter. FliX and FlbD homologues are present in several
      polar-flagellated bacteria, indicating that these proteins constitute an
      evolutionarily conserved regulatory pair in organisms where flagellar biogenesis
      is likely to be under control of the cell division cycle.

PMID- 15491363
TI  - Modulation of the mtrCDE-encoded efflux pump gene complex of Neisseria
      meningitidis due to a Correia element insertion sequence.
AB  - The mtr (multiple transferable resistance) gene complex in Neisseria gonorrhoeae
      encodes an energy-dependent efflux pump system that is responsible for export of
      anti-bacterial hydrophobic agents. Expression of the mtrCDE operon in gonococci
      is negatively regulated by the MtrR protein. Hydrophobic agent resistance
      mediated by the mtr system is also inducible, which results from an AraC-like
      protein termed MtrA. In this work, we identified and characterized a pump similar
      to the gonococcal mtr system in various strains of Neisseria meningitidis. Unlike
      the situation with gonococci, the mtr system in meningococci is not subject to
      the MtrR or MtrA regulatory schemes. An analysis of the promoter region of the
      mtrCDE operon in a panel of meningococcal strains revealed the presence of one or
      two classes of insertion sequence elements. A 155-159 bp insertion sequence
      element known as the Correia element, previously identified elsewhere in the
      gonococcal and meningococcal genomes, was present in the mtrCDE promoter region
      of all meningococcal strains tested. In addition to the Correia element, a
      minority of strains had a tandemly linked, intact copy of IS1301. As described
      previously, a binding site for the integration host factor (IHF) was present at
      the centre of the Correia element upstream of mtrCDE genes. IHF was found to bind
      specifically to this site and deletion of the IHF binding site enhanced mtrC
      transcription. We also identified a post-transcriptional regulation of the mtrCDE
      transcript by cleavage in the inverted repeat of the Correia element, as
      previously described by Mazzone et al. [Gene278: 211-222 (2001)] and De Gregorio
      et al. [Biochim Biophys Acta 1576: 39-44 (2002)]for other Correia element. We
      conclude that the mtr efflux system in meningococci is subject to transcriptional
      regulation by IHF and post-transcriptional regulation by cleavage in the inverted
      repeat of the Correia element.

PMID- 15491364
TI  - A proline tRNA(CGG) gene encompassing the attachment site of temperate phage 16-3
      is functional and convertible to suppressor tRNA.
AB  - Several temperate bacteriophage utilize chromosomal sequences encoding putative
      tRNA genes for phage attachment. However, whether these sequences belong to genes
      which are functional as tRNA is generally not known. In this article, we
      demonstrate that the attachment site of temperate phage 16-3 (attB) nests within
      an active proline tRNA gene in Rhizobium meliloti 41. A loss-of-function mutation
      in this tRNA gene leads to significant delay in switching from lag to exponential
      growth phase. We converted the putative Rhizobium gene to an active amber
      suppressor gene which suppressed amber mutant alleles of genes of 16-3 phage and
      of Escherichia coli origin in R. meliloti 41 and in Agrobacterium tumefaciens
      GV2260. Upon lysogenization of R. meliloti by phage 16-3, the proline tRNA gene
      retained its structural and functional integrity. Aspects of the co-evolution of
      a temperate phage and its bacterium host is discussed. The side product of this
      work, i.e. construction of amber suppressor tRNA genes in Rhizobium and
      Agrobacterium, for the first time widens the options of genetic study.

PMID- 15491365
TI  - HpaB from Xanthomonas campestris pv. vesicatoria acts as an exit control protein
      in type III-dependent protein secretion.
AB  - The hrp (hypersensitive response and pathogenicity) gene cluster of the plant
      pathogenic bacterium Xanthomonas campestris pv. vesicatoria encodes a type III
      secretion (TTS) system, which injects bacterial effector proteins into the plant
      cell. Here, we characterized hpaB (hpa, hrp-associated), which encodes a
      pathogenicity factor with typical features of a TTS chaperone. We show that HpaB
      is important for the efficient secretion of at least five effector proteins but
      is dispensable for the secretion of non-effectors such as XopA and the TTS
      translocon protein HrpF. GST pull-down assays revealed that HpaB interacts with
      two unrelated effector proteins, AvrBs1 and AvrBs3, but not with XopA. The HpaB
      binding site is located within the first 50 amino acids of AvrBs3. This region
      also contains the targeting signal for HpaB-dependent secretion, which is missing
      in HrpF and XopA. Intriguingly, the N-termini of HrpF and XopA target the
      AvrBs3Delta2 reporter for translocation in a DeltahpaB mutant but not in the wild
      type strain. This indicates that HpaB plays an essential role in the exit control
      of the TTS system. Our data suggest that HpaB promotes the secretion of a large
      set of effector proteins and prevents the delivery of non-effectors into the
      plant cell.

PMID- 15491367
TI  - Release of DNA into the medium by competent Streptococcus pneumoniae: kinetics,
      mechanism and stability of the liberated DNA.
AB  - The release of chromosomal DNA into culture media has been reported for several
      naturally transformable bacterial species, but a direct link between competence
      development and the liberation of DNA is generally lacking. Based on the analysis
      of strains with mutations in competence-regulatory genes and the use of
      conditions favouring or preventing competence, we provide evidence that DNA
      release is triggered by the induction of competence in Streptococcus pneumoniae.
      Kinetic analyses revealed that whereas competence was maximal 20 min after
      addition of competence-stimulating peptide, and then decreased, the amount of
      liberated DNA continued to increase and reached a maximum in stationary phase,
      when cells are no longer competent for DNA uptake. These data are not consistent
      with the proposal that release of DNA by a fraction of the population is
      coordinated with uptake by the remainder. Moreover, we observed that an
      unidentified DNase was specifically induced or released in competent cultures,
      and that together with the major pneumococcal endonuclease, EndA, it could
      degrade released DNA. Nearby complete abolition of release in a mutant lacking
      both the major autolysin, LytA, and the autolytic lysozyme, LytC, indicated that
      DNA liberation occurs by LytA-LytC-dependent cell lysis. These observations
      suggest that competence-dependent DNA release is one facet of a more general
      phenomenon of sensitization to autolysis that reaches its maximum in stationary
      phase.

PMID- 15491366
TI  - The role of H-NS in silencing F transfer gene expression during entry into
      stationary phase.
AB  - The conjugative ability of the F plasmid of Escherichia coli is highly growth
      phase dependent, with plasmid transfer efficiency dropping rapidly as donor cells
      progress through the growth cycle towards stationary phase. Transfer is dependent
      on the expression of the plasmid transfer (tra) genes, which are controlled by
      three plasmid-encoded regulatory proteins: TraJ, TraY and TraM. Here, we show
      that the nucleoid-associated host protein, H-NS, acts to repress the expression
      of traM and traJ as cells enter stationary phase, thereby decreasing mating
      ability to barely detectable levels. Sequence analysis identified regions of
      predicted intrinsic curvature, to which H-NS preferentially binds, at the
      promoters of both traM and traJ. H-NS binding at these regions was then confirmed
      by electrophoretic mobility shift and DNase I protection footprinting assays.
      Immunoblot assays displayed a significant increase in TraJ and TraM levels in an
      hns mutant strain. These findings were further supported by Northern and primer
      extension analyses which showed that whereas both genes were only expressed in
      early exponential phase in wild-type cells, hns mutant cells exhibited drastic
      derepression throughout the growth cycle. Transcriptional fusion studies of the
      individual promoters demonstrated that H-NS-mediated repression was observed when
      the promoters of both traM and traJ were present in cis to each other. This
      suggests that H-NS may bind to an extended region of the F plasmid, acting as a
      regional silencer of promoters for traJ and traM.

PMID- 15491368
TI  - The ColR-ColS two-component signal transduction system is involved in regulation
      of Tn4652 transposition in Pseudomonas putida under starvation conditions.
AB  - Bacteria use two-component signal transduction pathways to sense both
      extracellular and intracellular environment and to coordinate cellular events
      according to changing conditions. Adaptation can be either physiological or
      genetical. Here, we present evidence that a genome reorganization process such as
      transposition can be controlled by certain environmental cues sensed by a two
      component signal transduction system. We demonstrate that transposition-dependent
      accumulation of phenol-utilizing mutants is severely decreased in Pseudomonas
      putida defective in a two-component system colRS. Translocation of Tn4652 is
      decreased both in colR- and colS-defective strains, indicating that signal
      transduction from a histidine kinase ColS to a response regulator ColR is
      necessary for the activation of Tn4652 in bacteria starving on phenol. However,
      overexpression of ColR in a colS-defective strain restores Tn4652 transposition,
      suggesting that absence of the signal from ColS can be compensated by an elevated
      amount of ColR. In vitro analysis of purified ColR and ColS proteins evidenced
      that they constitute a functional phosphorelay. Site-directed mutagenesis
      revealed that a conserved H221 can be the phosphoryl-accepting residue in ColS
      and that aspartate residues D8 and D51 of ColR are necessary for the
      phosphotransfer from ColS to ColR. To our knowledge, Tn4652 is the first
      bacterial transposon regulated by a two-component system. This finding indicates
      that transpositional activity can respond to signals sensed and processed by the
      host.

PMID- 15491369
TI  - Integration host factor is involved in transcriptional regulation of the Brucella
      abortus virB operon.
AB  - Type IV secretion systems (T4SSs) are multicomponent machineries that play an
      essential role in pathogenicity of many facultative intracellular bacteria. The
      virB operon of Brucella abortus codes for a T4SS essential for virulence and
      intracellular multiplication. Here, virB expression analyses carried out using
      lacZ transcriptional fusions showed that virB promoter (PvirB) is temporally
      activated within J774 cells. Primer extension experiments revealed that virB
      transcription starts at 27 bp upstream of the first gene of the virB operon.
      Structural analyses showed that PvirB and regulatory sequences involved in
      intracellular regulation span 430 bp upstream of the transcription start site. A
      protein able to bind PvirB was isolated and identified. This protein, homologue
      to integration host factor (IHF), specifically interacts with PvirB and induces a
      DNA bending with an angle of 50.36 degrees . DNAse I footprinting experiments
      showed that IHF protects a 51 bp region that contains two overlapped IHF binding
      consensus motifs. VirB expression experiments carried out with PvirB-lacZ fusions
      showed that in B. abortus IHF participates in the regulation of PvirB activity
      during the intracellular and vegetative growth in different media. A mutant
      strain with a 20 bp IHF binding site replacement failed to turn on the virB
      operon during the initial stages of macrophage infection and displayed severe
      intracellular multiplication defects. These data indicate that IHF plays a key
      role during intracellular virB operon expression being required for the
      biogenesis of the endoplasmic reticulum-derived replicative vacuole.

PMID- 15491370
TI  - The response regulator SsrB activates transcription and binds to a region
      overlapping OmpR binding sites at Salmonella pathogenicity island 2.
AB  - OmpR activates expression of the two-component regulatory system located on
      Salmonella pathogenicity island 2 (SPI-2) that controls the expression of a type
      III secretion system, as well as many other genes required for systemic infection
      in mice. Measurements of SsrA and SsrB protein levels under different growth
      conditions indicate that expression of these two components is uncoupled, i.e.
      SsrB is produced in the absence of ssrA and vice versa. This result was suggested
      from our previous studies, in which two promoters at ssrA/B were identified. The
      isolated C-terminus of SsrB binds to DNA and protects regions upstream of ssrA,
      ssrB and srfH from DNase I digestion. Furthermore, the C-terminus of SsrB alone
      is capable of activating transcription in the absence of the N-terminus. Results
      from beta-galactosidase assays indicate that the N-terminal phosphorylation
      domain inhibits the C-terminal effector domain. A previous study from our
      laboratory reported that ssrA-lacZ and ssrB-lacZ transcriptional fusions were
      substantially reduced in an ssrB null strain. Results from DNase I protection
      assays provide direct evidence that SsrB binds at ssrA and ssrB, although the
      binding sites lie within the transcribed regions. Additional regulators clearly
      affect gene expression at this important locus, and here we provide evidence that
      SlyA, a transcription factor that contributes to Salmonella virulence, also
      affects ssrA/B gene expression.

PMID- 15491371
TI  - Origin pairing ('handcuffing') and unpairing in the control of P1 plasmid
      replication.
AB  - The P1 plasmid origin has an array of five binding sites (iterons) for the
      plasmid-encoded initiator protein RepA. Saturation of these sites is required for
      initiation. Iterons can also pair via their bound RepAs. The reaction, called
      handcuffing, is believed to be the key to control initiation negatively. Here we
      have determined some of the mechanistic details of the reaction. We show that
      handcuffed RepA-iteron complexes dissociate when they are diluted or challenged
      with cold competitor iterons, suggesting spontaneous reversibility of the
      handcuffing reaction. The complex formation increases with increased RepA
      binding, but decreases upon saturation of binding. Complex formation also
      decreases in the presence of molecular chaperones (DnaK and DnaJ) that convert
      RepA dimers to monomers. This indicates that dimers participate in handcuffing,
      and that chaperones are involved in reversing handcuffing. They could play a
      direct role by reducing dimers and an indirect role by increasing monomers that
      would compete out the weaker binding dimers from the origin. We propose that an
      increased monomer to dimer ratio is the key to reverse handcuffing.

PMID- 15491373
TI  - Abstracts for the 30th Annual Meeting of the International Society for Pediatric
      and Adolescent Diabetes (ISPAD), Singapore, 3-6 November 2004.

PMID- 15491374
TI  - Effects of bifidobacterium breve supplementation on intestinal flora of low birth
      weight infants.
AB  - BACKGROUND: It is known that the bifidobacteria flora play important roles in
      mucosal host defense and can prevent infectious diseases. Because bacterial
      populations develop during the first day of life, the authors examined whether
      the early administration of bifidobacteria has a positive effect on the health of
      low birth weight infants. METHODS: The effects of oral administration of
      Bifidobacterium breve (B. breve) supplements were studied in a controlled trial
      with low birth weight infants (average birth weight 1489 g). The infants were
      divided into three groups: Group A and B received a dose of 1.6 x 10(8) cells of
      B. breve supplement twice a day, commencing either from several hours after birth
      (group A) or 24 h after birth (group B). Group C, the control group, received no
      supplement. RESULTS: There were no significant differences in birth weight,
      treatment with antibiotics, and the starting time of breast-feeding among the
      three groups. A Bifidobacterium-predominant flora was formed at an average of 2
      weeks after birth in group A and at an average of 4 weeks after birth in group B,
      while no Bifidobacterium was isolated in eight out of 10 infants in group C
      during the observation period of 7 weeks. In comparison between group A and B,
      Bifidobacterium was detected significantly earlier in group A, and the number of
      Enterobacteriaceae present in the infants at 2 weeks after birth was
      significantly lower in group A. CONCLUSION: The results of the present study
      suggest that very early administration of B. breve to low birth weight infants is
      useful in promoting the colonization of the Bifidobacterium and the formation of
      a normal intestinal flora.

PMID- 15491375
TI  - Gastroesophageal reflux disease beyond infancy.
AB  - BACKGROUND: Children beyond infancy (>12 months of age) rarely have
      gastroesophageal reflux disease (GERD). Underlying diseases may contribute to the
      persistence of GERD from infancy to childhood. This study compares the clinical
      course of children with GERD with and without underlying diseases. METHODS: The
      authors studied the role of underlying diseases responsible for GERD in children
      beyond infancy by a retrospective analysis. From 1985 to 2000, GERD was confirmed
      in 34 children beyond infancy in the National Taiwan University (median age 2.5
      years, range 1.1-9.7 years), according to the inclusion criteria of reflux
      symptoms and the fraction of pH < 4 above 5% in the 24-h esophageal pH study. The
      patients were divided into two groups: those without underlying diseases (n=10)
      and those with underlying diseases (n=24). The follow-up duration was 0.5-17.1
      years (median 4.5 years). RESULTS: The underlying diseases responsible for GERD
      in 24 children included neurological impairment (n=14), repaired esophageal
      atresia (n=2), hiatal hernia (n=3), repaired congenital diaphragmatic hernia
      (n=2), and congenital heart disease (n=3). At the end of the study, 9 of 10
      children with GERD beyond infancy and without underlying diseases were free of
      symptoms without any need for further medical treatment. In contrast, 10 of 14
      children with neurological disorders had persisting reflux symptoms (Kaplan-Meier
      analysis, P=0.02, log-rank test). CONCLUSIONS: Neurological impairment and
      esophageal or diaphragmatic anatomic abnormalities were frequently associated
      with GERD beyond infancy. Children with underlying diseases, especially with
      neurological impairment, ran a refractory course, while those without underlying
      diseases enjoyed a longer symptom-free life.

PMID- 15491376
TI  - Sulthiame in childhood epilepsy.
AB  - BACKGROUND: Sulthiame is a central carbonic anhydrase inhibitor found to be
      effective for both partial and generalized seizures. It has been in use in some
      European countries and in Israel for over 30 years. The aim of the present study
      was to evaluate the efficacy and tolerability of sulthiame in childhood epilepsy
      by conducting a multicenter, retrospective study of patients who received this
      drug. METHODS: The charts of 125 consecutive epilepsy patients treated with
      sulthiame as monotherapy or add-on therapy were reviewed. RESULTS: Twenty-nine
      out of 39 patients with benign focal epilepsy of childhood became seizure-free.
      Total seizure control was also achieved in 17 of 42 patients with symptomatic,
      non-refractory localization-related epilepsy, and in all 10 cases with juvenile
      myoclonic epilepsy. Complete normalization of the EEG occurred in 13 of 20
      patients with benign partial epilepy of childhood. Side-effects were minimal and
      caused discontinuation of treatment in only seven children. CONCLUSION: The high
      tolerability, efficacy, convenience of use and low cost suggest that sulthiame
      should become a first line drug in the benign partial epilepsies of childhood and
      juvenile myoclonic epilepsy. It also has a role as add-on treatment in other
      partial and myoclonic epilepsies.

PMID- 15491377
TI  - Height-specific body mass index reference curves for Japanese children and
      adolescents 5-17 years of age.
AB  - BACKGROUND: Body mass index (BMI) reference values in consideration of height
      variation have not previously been reported. This study established height
      specific BMI reference curves for Japanese children and adolescents aged from 5
      to 17 years. METHODS: The 2001 nationwide survey data were utilized for the
      study. First, the range of variation in BMI corresponding to height (mean +/-
      2SD) at each age was compared with the range of variation in BMI corresponding to
      age (from minimum to maximum) at every cm height. Second, various age groups were
      combined, and percentile values of BMI (3rd, 5th, 15th, 50th, 85th, 95th, and
      97th) were calculated for every cm height, regardless of age, and height-specific
      BMI reference values (males 100-179 cm, females 100-169 cm) were prepared.
      RESULTS: Variation in BMI due to variation in height at each age was
      significantly (P <0.05) greater than variation in BMI due to age at every cm
      height [males, 12.7 +/- 0.4 vs 9.2 +/- 0.4; females, 11.7 +/- 0.8 vs 8.8 +/- 0.3
      (mean +/- SE)]. CONCLUSION: Although the use of standard values established in
      consideration of age and height is desirable for BMI-based guidelines for
      determining childhood overweight and obesity, to simplify the procedure for
      practical use, it is necessary to establish standard values by height, not by
      age. Height-specific BMI reference curves are useful for BMI-based evaluation of
      childhood overweight and obesity in the school health service and follow-up of
      obese children until adulthood.

PMID- 15491378
TI  - Body mass index of children from the United Kingdom diagnosed with pervasive
      developmental disorders.
AB  - BACKGROUND: The aim of the present study was to ascertain the Body Mass Index
      (BMI) (kg m(-2)) derived from parental reports of height (metres) and weight
      (kilograms) of a pilot sample of boys born and resident in the UK diagnosed with
      pervasive developmental disorders (PDD). METHOD: Analysis of parental reporting
      of height and weight measurements in boys (n=50) diagnosed with PDD and
      comparison with age and sex-matched reference populations. RESULTS: The majority
      of patients were above the 50th percentile for height (70%), weight (74%) and BMI
      (80%) with 21% exceeding cut-off points for overweight and 10% for clinical
      obesity. There were no significant differences (P < 0.05) found between PDD
      subgroups for any of the measures. CONCLUSION: Further studies are required to
      validate findings of skewed height, weight and BMI data in PDD.

PMID- 15491379
TI  - Serum leptin concentrations in children with mild protein-energy malnutrition and
      catch-up growth.
AB  - BACKGROUND: The aim of the present study was to clarify the relationship between
      changing nutritional anthropometric data and serum leptin concentrations during
      the catch-up growth process in children. METHODS: Thirty children with mild
      protein-energy malnutrition (PEM) were followed for 6 months and their
      anthropometric measurements and serum leptin concentrations were recorded during
      follow up. RESULTS: Twenty-two (73.3%) of the 30 children showed catch-up growth.
      All parameters and serum leptin concentrations increased during the period of
      catch-up growth. In the remaining eight children, weight for height, percentage
      standard body mass index, percentage standard body height and mean serum leptin
      concentrations did not show any significant increase at the 6 month follow-up.
      Mean serum leptin concentration was higher in children with catch-up growth than
      in the controls. CONCLUSION: During recovery from malnutrition, leptin
      concentrations increase in relation to fat mass if the fat mass reaches a
      critical point, and leptin might trigger catch-up growth with its regulator
      effects on growth. Although weight gain was noted in both groups, an increase in
      leptin concentration was observed only in children who showed catch-up growth.
      More interestingly, the mean leptin concentration was much higher in children
      with PEM who had catch-up growth compared to the control group and in children
      who failed to have catch-up growth. In children with catch-up growth, the higher
      serum leptin concentrations compared to healthy children and to children without
      catch-up growth despite significant weight gain suggests that leptin affects
      nutritional status in catch-up growth as a dynamic process, rather than merely
      being an index of body fat content.

PMID- 15491380
TI  - Additive effects of dexamethasone in nebulized salbutamol or L-epinephrine
      treated infants with acute bronchiolitis.
AB  - BACKGROUND: Although it is the most common lower respiratory infection of
      infancy, the optimal treatment for acute bronchiolitis is still controversial.
      The aim of this study was to compare the early and late effects of nebulized L
      epinephrine (EPI) and intramuscular dexamethasone (DEX) combination therapy with
      nebulized salbutamol (SAL) and dexamethasone combination and bronchodilators
      alone in outpatients with acute bronchiolitis. METHODS: A total of 69 infants
      aged 2-21 months who were admitted to the Pediatrics Department of the Faculty of
      Medicine, Mersin University, with acute bronchiolitis were included in a
      randomized, placebo-controlled, prospective trial study. Patients were assigned
      to receive either nebulized L-epinephrine (3 mg) or salbutamol (0.15 mg/kg) and
      15 min later, either dexamethasone 0.6 mg/kg or placebo (PLA), intramuscularly,
      in a double-blind randomized fashion. The study groups were: epinephrine +
      dexamethasone group (group 1, n=23), salbutamol + dexamethasone group (group 2,
      n=23), epinephrine + placebo group (group 3, n=11), and salbutamol + placebo
      group (group 4, n=12). The outcome measures were heart rate, respiratory rate and
      Respiratory Distress Assessment Instrument (RDAI) score determined at 30, 60, 90
      and 120 min, 24 h, and 5 days after the first therapy. Patients were then
      followed-up during the subsequent 2 months for the prevalance of respiratory
      complaints regarding bronchial hyperreactivity. RESULTS: There were no
      significant differences between the outcome variables of the four groups within
      the first 120 min and at 24 hours, or between the rates of requirement of a
      second dose of the same bronchodilator. However, fifth day RDAI score values of
      both DEX groups were significantly lower than that of SAL + PLA group (P=0.000
      and P=0.01, respectively). The fifth day score value of group 1 was also
      significantly better than that value of EPI + PLA group but not different from
      group 2. CONCLUSIONS: A single dose of intramuscular dexamethasone added to
      nebulized L-epinephrine, or salbutamol therapies resulted in better outcome
      measures than bronchodilators alone in the late phase (fifth day) of mild to
      moderate degree bronchiolitis attack. However, effects of EPI + DEX combination
      was not different from SAL + DEX combination.

PMID- 15491381
TI  - Non-specific host response markers in the differentiation between pneumococcal
      and viral pneumonia: what is the most accurate combination?
AB  - BACKGROUND: Serum C-reactive protein (CRP), blood white cell count (WBC), serum
      procalcitonin (PCT) and erythrocyte sedimentation rate (ESR) were measured in 132
      children hospitalized for community-acquired pneumonia. Serological evidence for
      viral infection was found in 38 cases and for pneumococcal infection in 41 cases,
      and the infiltrate was alveolar in 46 cases and interstitial in 86 cases. The aim
      of the present paper was to determine if there is a combination of these four
      host response markers and chest radiograph findings suitable for differentiating
      pneumococcal from viral etiology of pneumonia. METHODS: The 50th, 75th and 90th
      percentiles of CRP, WBC, ESR and PCT in the total group of 132 patients were
      calculated. By using these cut-off limits, the likelihood ratios of a positive
      test result were calculated for the possible combinations of CRP, WBC, ESR and
      PCT, and the likelihood ratio was 1.50 or more for six combinations. RESULTS: The
      highest likelihood ratio (1.74) was achieved with the combination CRP > 90th (80
      mg/L) or WBC > 75th (17.0 x 10(9)/L) or PCT > 75th (0.84 microg/L) or ESR > 90th
      (63 mm/h) percentile. For this combination, the sensitivity was 61% and the
      specificity 65%. When the 90th percentile cut-off limit was applied also for WBC
      (>22 x 10(9)/L) and PCT (>1.8 microg/L), the specificity increased to 76%, but
      the sensitivity decreased to 37%. When the presence of an alveolar infiltration
      was included in the combination, the likelihood ratio was 1.89; the specificity
      was as high as 82% and the sensitivity as low as 34%. CONCLUSIONS: CRP, PCT, WBC
      and ESR have only limited value in differentiating pneumococcal or other
      bacterial pneumonia from viral pneumonia. If there was a high value in at least
      one of the markers (CRP > 80 mg/L, PCT > 1.8 microg/L, WBC > 22 x 10(9)/L or ESR
      > 60 mm/h), viral infections were rare. There was no combination of these markers
      which was sufficiently sensitive and specific to be used in clinical pediatric
      practice.

PMID- 15491382
TI  - Rapid diagnosis of bacterial meningitis by using multiplex PCR and real time PCR.
AB  - BACKGROUND: The purpose of the present study was to improve a method for a rapid
      identification of bacteria in bacterial meningitis by using multiplex polymerase
      chain reaction (PCR). METHODS: Ten species of bacteria which cause meningitis in
      children were investigated, and cerebrospinal fluid from patients with purulent
      meningitis was studied. The ribosomal RNA genes of bacteria are essential, and
      are highly conserved in the bacterial kingdoms with consensus region. The 23S
      rRNA region shows a larger variation among species than in the 16S rRNA region.
      The authors set primers in the universal region and specific region of 23S rRNA,
      then amplified these regions by multiplex PCR and real-time PCR. RESULTS: All
      species of bacteria showed one band by PCR using universal primer. Haemophilus
      influenzae and Streptococcus pneumoniae showed two bands by multiplex PCR using a
      combination of universal primers and specific primers. The authors detected H.
      influenzae within 15 min by using real-time PCR. CONCLUSION: It was possible to
      identify clinically significant bacterial species in cerebrospinal fluid by
      multiplex PCR, and to identify H. influenzae by real-time PCR within a short
      period.

PMID- 15491383
TI  - Effect of total attending period on infection episode rate in a child-care
      center.
AB  - BACKGROUND: Attendance to a child-care facility is known to be associated with
      increased rate of episodes of infectious diseases in children. This retrospective
      cohort study investigates the infection episode rate and the effect of total
      attending period on infection episode rates in a child-care center (Gulveren
      Child-Care Center, Ankara, Turkey), at a stable environmental condition, over a 7
      year follow-up period. METHODS: During the study period, 288 children attended
      the center and enrolled. Sex, total duration of breastfeeding, starting age at
      the center, total duration of attendance, and the type and frequency of
      infections diseases were recorded. Episode rates were calculated for each child.
      RESULTS: The mean starting age at the child care center was 4.1 +/- 0.7 years
      (range: 2.5-5.8 years); the mean total duration of attendance at the center was
      20.4 +/- 9.9 months. Over the study period, 1000 infection episodes were
      detected. The general infection episode rate was calculated as 2.04/child per
      year. In bivariate analysis, children with longer attendance period (> or =12
      months), and a younger starting age at the center (<4 years of age) had lower
      'moderate general infection' (> or =3 episode/child per year) episode rates than
      those of other groups. In multiple logistic regression analysis, only total
      attending period in the center was significantly associated with 'moderate' level
      general infection episode rate. The presence of asthma slightly increased the
      lower respiratory tract infections episode rate in bivariate analysis, and was
      the only significant predictor of LRTI episode rate in multivariate analysis.
      CONCLUSIONS: The results of the present study show that among children attending
      a single facility, longer periods of attendance at the facility was associated
      with a decreased risk of general infection episode, regardless of starting age at
      the center. Additional cohort studies are needed to determine whether this
      reduction in general infection episode rate extends into school-age years and
      whether children moving between different centers affects the incidence of
      infectious episodes.

PMID- 15491384
TI  - Effects of leptin and dexamethasone on long and short leptin receptor mRNA.
AB  - BACKGROUND: Leptin exerts its effects by using both long (OB-Rb) and short (OB
      Ra) receptors. Although leptin resistance or insensitivity is reported to be a
      cause of human obesity, there have not been enough studies to clarify regulation
      of leptin receptors. METHODS: The authors studied leptin receptor regulation by
      leptin and dexamethasone in the human hepatocellular carcinoma cell (HepG2).
      Using a quantitative RT-PCR technique, the authors demonstrate expression of OB
      Ra and OB-Rb mRNA after the incubation for 24 h with leptin or dexamethasone at
      various concentrations (10(-9)-10(-6) M). RESULTS: Leptin (10(-7)-10(-6) M)
      significantly inhibited expression of OB-Rb mRNA, with maximum inhibition (43% of
      control) at 10(-6) M. Expression of OB-R219.1 and OB-R219.3, two short isoforms
      of leptin receptor, were also reduced in cells treated with leptin most
      remarkably at 10(-7) M for OB-R219.1 (44% of the control) and at 10(-6) M for Ob
      R219.3 (49% of the control). In contrast, dexamethasone (10(-8)-10(-6) M)
      significantly increased OB-Rb mRNA levels, with a maximum increase (204% of the
      control) at 10(-7) M, and OB-R219.1 and OB-R219.3 mRNA expression was also
      markedly increased at 10(-9)-10(-6) M. The peak values were 254% of the control
      for OB-R219.1 and 246% of the control for OB-R219.3 at 10(-7) M. CONCLUSIONS: In
      HepG2 cells, leptin inhibits and dexamethasone increases OB-Ra and OB-Rb mRNA
      expression. It is suggested that glucocorticoids as well as leptin itself
      contribute to regulatory effects of leptin through changes in gene expression of
      leptin receptors.

PMID- 15491385
TI  - Screening for G71R mutation of the UGT1A1 gene in the Javanese-Indonesian and
      Malay-Malaysian populations.
AB  - BACKGROUND: There are significant differences in the prevalence and severity of
      neonatal jaundice among various populations. Recently, it has been reported that
      a mutation of the UGT1A1 gene, glycine to arginine at codon 71 (G71R), is related
      to the development of neonatal jaundice in East Asian populations. However,
      whether the G71R mutation contributes to the high incidence of neonatal jaundice
      in different Asian populations remains unknown. The authors screened for this
      mutation in the Javanese-Indonesian and Malay-Malaysian populations. METHODS: One
      hundred and thirty-six subjects were enrolled in this study: 68 Javanese
      Indonesian adults and 68 Malay-Malaysian newborns (32 with jaundice and 36
      without jaundice). Denaturing high-performance liquid chromatography (DHPLC) was
      used to screen for the G71R mutation, and the results were confirmed by
      nucleotide sequencing analysis. RESULTS: With DHPLC, the authors easily and
      clearly detected seven subjects carrying the G71R mutation: two Javanese
      Indonesian adults and five Malay-Malaysian newborns. In the 68 Javanese
      Indonesian adults, the genotype distribution for G71R mutation was 66 G/G, two
      G/R and no R/R genotypes, and the mutated allele frequency was 0.015. In the 68
      Malay-Malaysian newborns, genotype distribution for the mutation was 63 G/G, five
      G/R and no R/R genotypes, and the mutated allele frequency was 0.037. The
      genotype distributions did not differ significantly between the newborns with
      jaundice and those without jaundice. CONCLUSION: The G71R mutation is present,
      but very rare, in Javanese-Indonesians and Malay-Malaysians. Thus, G71R mutation
      may not contribute to the high incidence of the neonatal jaundice in South-east
      Asian populations. DHPLC analysis is a very useful method for detecting the G71R
      mutation.

PMID- 15491386
TI  - Glomerular dysfunction, independent of tubular dysfunction, induced by
      antineoplastic chemotherapy in children.
AB  - BACKGROUND: For the purpose of studying renal side-effects induced by
      antineoplastic agents, the authors examined glomerular injury as well as tubular
      injury of patients with chemotherapy. METHODS: Thirteen patients underwent a
      combined total of 64 courses of chemotherapy. Urinary albumin, beta2
      microglobulin (beta2-MG), N-acetyl-beta-glucosaminidase (NAG) and urinary protein
      were measured before and serially after chemotherapy. RESULTS: The values of
      albumin/creatinine (albumin/cre) ratio and beta2-MG/creatinine (beta2-MG/cre)
      ratio after chemotherapy were higher than those before chemotherapy (P <0.01).
      NAG/creatinine (NAG/cre) ratio and creatinine clearance (Ccr) were not different.
      These were also examined before the next course of chemotherapy and were compared
      with those of control children. Albumin/cre ratio was significantly different (P
      <0.01). beta2-MG/cre ratio and NAG/cre were not different. Furthermore, in
      patients with normal beta2-MG/cre, the albumin/cre ratio was significantly higher
      than in control children. CONCLUSIONS: These results indicate that antineoplastic
      agents can not only induce tubular dysfunction but also glomerular dysfunction,
      which is persistent and independent of tubular dysfunction.

PMID- 15491387
TI  - Combined therapy of enalapril and losartan attenuates histologic progression in
      immunoglobulin A nephropathy.
AB  - BACKGROUND: It has been reported that combined therapy of angiotensin converting
      enzyme inhibitor and angiotensin receptor blocker significantly decreases
      proteinuria in immunoglobulin A (IgA) nephropathy. However, histologic
      alterations following the therapy have not been reported. METHODS: A total of
      nine Japanese children with severe proteinuric IgA nephropathy who received a
      prompt immunosuppressive therapy were enrolled the study, four of whom received a
      combined therapy of angiotensin converting enzyme inhibitor, enalapril and
      angiotensin receptor blocker, losartan (Group A), while the remaining five did
      not (Group B). All underwent renal biopsy before and approximately 12 months
      after the first renal biopsy. RESULTS: At presentation, urine protein excretion
      and the histologic indices of mean activity index, mean chronicity index and
      tubulointerstitial scores did not show a statistical difference between the two
      groups: Group A (2.6 +/- 0.6 g/day; mean activity index, 5.0 +/- 1.0; mean
      chronicity index, 5.0 +/- 1.0; tubulointerstitial scores, 4.3 +/- 1.0) and Group
      B (2.2 +/- 0.6 g/day; mean activity index, 4.8 +/- 0.8; mean chronicity index,
      4.8 +/- 1.3; tubulointerstitial scores, 3.6 +/- 0.5, respectively). All had
      normal blood pressure and renal function. Urine protein excretion and the
      activity index decreased at the second renal biopsy, while the chronicity index
      and the tubulointerstitial scores slightly increased or remained unchanged. In
      comparison with Group B, a significant suppression in increasing the chronicity
      index and the tubulointerstitial scores obtained at the second renal biopsy were
      observed in Group A [Group A: 4.3 +/- 1.2 and 3.0 +/- 0.0, respectively, vs Group
      B: 6.0 +/- 0.7 and 4.4 +/- 0.9, respectively (P < 0.05)]. One patient in Group B
      developed chronic renal insufficiency thereafter. CONCLUSIONS: Although only a
      small number of patients were examined, these clinical findings suggest that a
      combined therapy of enalapril and losartan may attenuate histologic progression
      in at least a proportion of patients with severe proteinuric IgA nephropathy.

PMID- 15491388
TI  - Spontaneous pneumothorax in children in the South-east of Turkey.
AB  - BACKGROUND: The purpose of the present study was to investigate the etiological
      factors, symptomatology, management and outcome of spontaneous pneumothorax in
      children aged <15 years. METHODS: The authors' reviewed the records of 44
      children with spontaneous pneumothorax between January 1990 and February 2002.
      RESULTS: The median age was 4.6 years (range 2 months-14 years), and 51% were
      male. Breathlessness and coughing were the most common symptoms. All
      pneumothoraces were initially managed by closed tube drainage. Thirty-seven (84%)
      of the children responded well and were cured of pneumothorax with closed tube
      thoracostomy alone. Seven children (16%) underwent thoracotomy. The median
      hospital stay was 12.9 days. There were two deaths from respiratory failure. Six-
      to 96-month follow-up information was available for 32 patients, and only one
      recurrence was found. CONCLUSIONS: Lung infections were the most frequently
      observed underlying pathology in the patients studied. Closed tube thoracostomy
      alone was sufficient for the majority of patients.

PMID- 15491389
TI  - Abnormal steroidogenesis in three patients with Antley-Bixler syndrome: apparent
      decreased activity of 17alpha-hydroxylase, 17,20-lyase and 21-hydroxylase.
AB  - BACKGROUND: Antley-Bixler syndrome (ABS) is characterized mainly by abnormal
      skeletal morphogenesis such as craniosynostosis and radiohumeral synostosis, and
      by ambiguous genitalia in some cases. The mechanisms resulting in these
      deformities have not been determined. METHODS: The adrenal and gonadal function
      of three Japanese ABS patients were evaluated. Patient 1 (17-year-old-male) had
      bilateral cryptoorchidism, delayed puberty and symptoms of glucocorticoid
      deficiency. Patient 2 (14-year-old male) and patient 3 (4-year-old female)
      presented with emaciation. Additionally, patient 3 had partial labial fusion and
      common urogenital sinus. In each patient, blood sampling for steroid analysis
      before and after rapid adrenocorticotropic hormone (ACTH) stimulation was carried
      out. Additionally, urinary steroids were quantified. Molecular analysis of CYP17
      and CYP21A2 were also performed. RESULTS: All patients showed elevated basal
      17alpha-deoxysteroid levels. Although the 17alpha-deoxysteroid levels further
      increased after rapid ACTH stimulation, 17alpha-hydroxysteroids including
      cortisol did not respond, suggesting impaired 17alpha-hydroxylation. Patient 1
      and patient 2 showed low adrenal androgen blood levels both before and after
      rapid ACTH stimulation. Patient 3 showed lower than normal excretions of urinary
      androgens. Additionally, a prolonged ACTH stimulation in patient 3 failed to
      elicit significant increase of adrenal androgens. These findings suggested
      impaired 17,20-lyase activity. In contrast to attenuated 17alpha
      hydroxycorticosteroids, notably cortisol, elevated 17alpha-hydroxyprogesterone
      (17OHP) levels were observed, not only in pubertal patients (1 and 2) but also in
      prepubertal patient 3, indicating impaired 21-hydroxylation. This assumption was
      supported by increased urinary 21-deoxycortisol metabolite excretion in patients
      2 and 3. With the exception of a heterozygous mutation of CYP17 in one of the
      patients, other mutations of this gene or CYP21A2 were identified in any of the
      patients. CONCLUSION: Combined decreased 17alpha-hydroxylation, 17,20-lyase
      activity and 21-hydroxylation was detected in three ABS patients. Considering
      that the enzymes responsible are all cytochrome P450 enzymes and that another
      cytochrome P450 enzyme, lanosterol 14alpha-demethylase, has recently been shown
      to be impaired in an ABS patient, we speculate that dysfunction of a system which
      commonly regulates cytochrome P 450 activity may be responsible for the ABS
      phenotype.

PMID- 15491390
TI  - Immunohistochemical study of apparently intact coronary artery in a child after
      Kawasaki disease.
AB  - BACKGROUND: Coronary arterial lesions (CAL) due to Kawasaki disease (KD) often
      show progressive intimal hyperplasia even many years after the disease. However,
      most patients have no CAL after the acute phase, and it is an important issue
      whether or not coronary arteries without CAL have significant intimal
      hyperplasia, and whether or not there is the potential for this to progress to
      stenosis and/or atherosclerosis. METHODS: The authors examined formalin-fixed
      specimens of the coronary arteries immunohistochemically, using antibodies
      against vascular growth factors (GFs), the receptors of transforming growth
      factor-beta (TbetaRs) and inducible nitric oxid synthesis (iNOS) in a KD patient
      without CAL, and also in four control patients: two with CAL due to KD and two
      without a history of KD. RESULTS: Vascular endothelial GFs, Platelet-derived
      growth factor-A (PDGF-A) and TbetaRs were expressed in the vascular smooth muscle
      cells of all patients. PDGF-A, transforming Gfbeta1 and iNOS were expressed in
      the intimal smooth muscle cells of the KD but not the normal coronary artery
      without a history of KD. The number of TbetaR-II-positive cells were fewer than
      TbetaR-I-positive cells in the intima of CAL due to KD, but the number was of
      both almost same in the intima of coronary artery without CAL after KD and in the
      normal coronary. CONCLUSION: The intact coronary artery 13 months after KD still
      showed the influence of the inflammation of KD. Although the authors speculate
      that the intimal proliferation will not continue beyond the acute phase, those
      patients may have a risk factor for atherosclerosis.

PMID- 15491391
TI  - Pharmacokinetic study of mizoribine in an adolescent with lupus nephritis.

PMID- 15491392
TI  - Hemoperitoneum versus bowel perforation in the extremely low birth weight infant.

PMID- 15491393
TI  - Postnatal remission of ocular, auditory, and somatic findings in Stickler
      syndrome.

PMID- 15491394
TI  - Kimura disease in a patient with Rubinstein-Taybi syndrome.

PMID- 15491395
TI  - Refractory autoimmune hemolytic anemia in a patient with chromosome 22q11.2
      deletion syndrome.

PMID- 15491396
TI  - EYA1 gene nonsense mutation in a Japanese family with branchio-oto-renal
      syndrome.

PMID- 15491397
TI  - Transient Pseudohypoaldosteronism in an infant with urinary tract anomaly.

PMID- 15491398
TI  - Septic pulmonary emboli presenting with deep venous thrombosis secondary to acute
      osteomyelitis.

PMID- 15491399
TI  - Effects of swimming training on physical fitness and water orientation in autism.

PMID- 15491401
TI  - The Bohr effect--a discovery 100 years ago, with intensive studies about the
      effect of protons on haemoglobin function still going on.

PMID- 15491402
TI  - Red blood cell pH, the Bohr effect, and other oxygenation-linked phenomena in
      blood O2 and CO2 transport.
AB  - The discovery of the S-shaped O2 equilibrium curve and the Bohr effect in 1904
      stimulated a fertile and continued research into respiratory functions of blood
      and allosteric mechanisms in haemoglobin (Hb). The Bohr effect (influence of
      pH/CO2 on Hb O2 affinity) and the reciprocal Haldane effect (influence of HbO2
      saturation on H+/CO2 binding) originate in the Hb oxy-deoxy conformational change
      and allosteric interactions between O2 and H+/CO2 binding sites. In steady state,
      H+ is passively distributed across the vertebrate red blood cell (RBC) membrane,
      and intracellular pH (pHi) changes are related to changes in extracellular pH, Hb
      O2 saturation and RBC organic phosphate content. As the Hb molecule shifts
      between the oxy and deoxy conformation in arterial-venous gas transport, it
      delivers O2 and takes up CO2 and H+ in tissue capillaries (elegantly aided by the
      Bohr effect). Concomitantly, the RBC may sense local O2 demand via the degree of
      Hb deoxygenation and release vasodilatory agents to match local blood flow with
      requirements. Three recent hypotheses suggest (1) release of NO from S-nitroso-Hb
      upon deoxygenation, (2) reduction of nitrite to vasoactive NO by deoxy haems, and
      (3) release of ATP. Inside RBCs, carbonic anhydrase (CA) provides fast hydration
      of metabolic CO2 and ensures that the Bohr shift occurs during capillary transit.
      The formed H+ is bound to Hb (Haldane effect) while HCO3- is shifted to plasma
      via the anion exchanger (AE1). The magnitude of the oxylabile H+ binding shows
      characteristic differences among vertebrates. Alternative strategies for CO2
      transport include direct HCO3- binding to deoxyHb in crocodilians, and high
      intracellular free [HCO3-] (due to high pHi) in lampreys. At the RBC membrane,
      CA, AE1 and other proteins may associate into what appears to be an integrated
      gas exchange metabolon. Oxygenation-linked binding of Hb to the membrane may
      regulate glycolysis in mammals and perhaps also oxygen-sensitive ion transport
      involved in RBC volume and pHi regulation. Blood O2 transport shows several
      adaptive changes during exposure to environmental hypoxia. The Bohr effect is
      involved via the respiratory alkalosis induced by hyperventilation, and also via
      the pHi change that results from modulation of RBC organic phosphate content. In
      teleost fish, beta-adrenergic activation of Na+/H+ exchange rapidly elevates pHi
      and O2 affinity, particularly under low O2 conditions.

PMID- 15491403
TI  - The Bohr effect of haemoglobin in vertebrates: an example of molecular adaptation
      to different physiological requirements.
AB  - The Bohr effect, i.e. the pH dependence of the oxygen affinity of haemoglobins
      (Hbs) from a variety of vertebrates, and its modulation by temperature and other
      heterotropic effectors has been reviewed. Haemoglobins from vertebrates were not
      reviewed following the usual classification (i.e. mammals, birds, etc.); instead
      we have selected several key examples of animals, which are confronted with a
      similar environmental situation therefore displaying a similar life style. Hence,
      the paper starts from a description of the general concepts at the basis of the
      Bohr effect as exemplified by human HbA and goes towards the analysis of the
      modulation mechanisms which have been observed in different animals in response
      to the needs induced by: (i) life in cold environments; (ii) diving behaviour;
      (iii) flight; and (iv) aquatic life. The emerging picture indicates a complex
      organization of the information contained in the Hb molecule, the oxygen-binding
      properties of which depend both on the intrinsic characteristics of the protein
      and on its heterotropic interactions with ligands such as protons (Bohr effect),
      small anions like chloride and organic phosphates. In addition, each one of the
      functional effects induced by binding of a given effector appears to be under the
      strict control of temperature that enhances or decreases its relative weight with
      respect to all the others. It is just by this sophisticated network of
      interactions that the Hb molecule is able to satisfy the physiological
      requirements of a multitude of organisms without changing dramatically its
      quaternary structure.

PMID- 15491404
TI  - New insights into the proton-dependent oxygen affinity of Root effect
      haemoglobins.
AB  - A long-standing puzzle with regard to protein structure/function relationships is
      the proton-dependent modification of haemoglobin (Hb) structure that causes
      oxygen to be unloaded from Root effect Hbs into the swim bladders and eyes of
      fish even against high oxygen pressure gradients. Although oxygen unloading in
      Root effect Hbs has generally been attributed to proton-dependent stabilization
      of the T-state, protonation of Root effect Hbs can alter their ligand affinities
      in both R- and T-state conformations and either stabilize the T-state or
      destabilize the R-state. The C-terminal residues that are so important in the
      Bohr effect of human Hb appear to be involved in the Root effects of some fish
      Hbs and not in others, indicating that several evolutionary pathways have
      resulted in expression of highly pH-dependent Hbs. New data are presented that
      show surprising similarities in the pH- and anion-dependence of sulfhydryl group
      reactivity and anaerobic oxidation of human and fish Hbs. The available evidence
      supports the concept that in both Bohr effect and Root effect Hbs a large steric
      component acts in addition to quaternary shifts between R and T conformations to
      regulate ligand affinity. Allosteric effectors moderate these steric effects
      within both R- and T-state conformations and allow for an elegant match between
      Hb function and the wide-ranging physiological needs of diverse organisms.

PMID- 15491405
TI  - Control of oxygen transport in the microcrustacean Daphnia: regulation of
      haemoglobin expression as central mechanism of adaptation to different oxygen and
      temperature conditions.
AB  - The pathway for oxygen, the control of oxygen transport and the role of
      haemoglobin expression for the physiological adaptation to different oxygen and
      temperature conditions were studied in the ecological model organism Daphnia
      magna. Ventilation of the inner walls of the carapace as the main gas exchange
      area as well as of the embryos in the brood pouch are controlled, oxygen
      dependent processes. The P(O2)-dependent increase of heart rate as well as
      perfusion rate during short-term, progressive hypoxia improves the circulatory
      oxygen transport within the body. The regulation of haemoglobin (Hb) expression
      is the central mechanism for a medium-term adaptation to hypoxia. Genetic control
      elements and oxygen conditions near the two Hb synthesis sites (fat cells,
      epipodite epithelial cells) determine, which types of Hb subunits and,
      accordingly, hetero-multimeric Hb macromolecules are produced. One synthesis site
      may respond mainly to internal, the other one to external oxygen conditions.
      Depending on environmental condition, either higher quantities of macromolecules
      of unchanged functionality (P50) or increasing amounts of macromolecules with
      higher oxygen affinity are synthesized. The Hb subunit DmHbA is probably of
      considerable importance for this functional change. The physiological benefits of
      haemoglobin in Daphnia are discussed. Physiological adaptation of Daphnia to
      different temperatures is also related to the control of oxygen transport
      processes with the regulation of haemoglobin expression again as a central
      mechanism.

PMID- 15491406
TI  - Positive inotropic and sustained anti-beta-adrenergic effect of diadenosine
      pentaphosphate in human and guinea pig hearts. Role of dinucleotide receptors and
      adenosine receptors.
AB  - AIM: Diadenosine polyphosphates are present intracellularly and in extracellular
      fluid due to release from secretory vesicles in platelets, chromaffin cells and
      other cells. This study investigates effects of diadenosine pentaphosphate (AP5A)
      on heart muscle function. METHODS: Contractile force amplitude and action
      potential duration at 90% repolarization (APD90) were measured after challenge
      with AP5A 50 microm or isoproterenol 50-70 nM in guinea pig papillary muscles.
      Isoproterenol was given immediately after AP5A-exposure or after 45 min washout.
      AP5A was combined with antagonists to the purinergic P2 receptor (suramin 100
      microm), the dinucleotide receptor [diinosine pentaphosphate 30 microm (IP5I)] or
      adenosine receptors [8-(P-sulfophenyl) theophylline 50 microm (8-SPT)]. RESULTS:
      Results are %-change (mean +/- SEM) from value before exposure. AP5A increased
      contractile force by 22 +/- 3%* (*P <0.05), and IP5I abolished this. AP5A
      prolonged APD90 by 7 +/- 2%*. AP5A significantly reduced response to
      isoproterenol acutely from 31 +/- 4* (controls) to 9 +/- 4% and after 45 min
      washout from 61 +/- 14* (controls) to 16 +/- 5%. 8-SPT abolished the sustained
      effect. Increase in contractile force by AP5A was confirmed in human atria
      trabecula preparations. CONCLUSION: AP5A increased contractile force and
      prolonged APD90. Contractile force increased by stimulation of the dinucleotide
      receptor in guinea pig myocardium. The sustained anti-beta-adrenergic effect of
      AP5A was due to adenosine receptor stimulation.

PMID- 15491407
TI  - Comparison of regional vasomotor responses to acetazolamide and CO2 in rabbit
      cerebrum and cerebellum, measured by a hydrogen clearance method.
AB  - AIM: Many investigators have proved the usefulness of acetazolamide provocation
      and the carbon dioxide test for assessment of the local cerebrovascular
      reactivity by measurement of the regional cerebral blood flow in patients with
      occlusive cerebrovascular disease. Data originating from a comparison of these
      two different vasomotor stimuli as concerns the differences in sensitivity to
      them in various parts of the central nervous system are scarce. Our aim was to
      compare the cerebral blood flow responses to hypercapnic and acetazolamide
      stimuli in different brain regions. METHODS: The cerebral blood flow was measured
      in the cerebrum (cortex and caudate nucleus) and cerebellum (cortex), as measured
      by a hydrogen clearance method in anaesthetized, artificially ventilated rabbits.
      RESULTS: In normocapnia, the cerebral blood flow values in the cerebrum and the
      cerebellum differed significantly. The cerebral blood flow responses to both
      vasodilatory stimuli were to be significantly higher in the cerebrum than in the
      cerebellum, but the relative increases, i.e. the mean relative reactivities, were
      similar in the different regions measured. CONCLUSION: The regional dissimilarity
      might explain to some extent the different sensitivities of the various brain
      areas to sudden blood pressure changes (infarction or haemorrhage). The results
      further suggest that heterogeneity in cerebrovascular reactivity should be
      considered in the assessment of vasoreactivity in patients with occlusive
      cerebrovascular disease. Since the comparison of the carbon dioxide and
      acetazolamide-induced cerebrovascular reactivities revealed a strong linear
      relationship, it was concluded that acetazolamide provocation is equivalent to
      the carbon dioxide test in the evaluation of cerebrovascular reactivity.

PMID- 15491408
TI  - Human motor compensations for thixotropy-dependent changes in muscular resting
      tension after moderate joint movements.
AB  - AIM: This study on healthy subjects explores history-dependent changes in the
      resting tension of relaxed wrist muscles after moderate joint excursions and the
      motor control consequences of these changes during voluntary wrist joint position
      maintenance. METHODS: Integrated surface electromyogram (IEMG) was recorded from
      wrist extensor/flexor muscles. Angular position and torque were recorded from the
      wrist joint. Changes in wrist flexor muscle resting tension were sensed by a
      force transducer pressed against the tendons. RESULTS: Consecutive stepwise
      changes (7.5 degrees ) in wrist joint position (within the dorsiflexed range)
      were either imposed on relaxed subjects or actively performed while the subjects
      under visual guidance tried to mimic the passive movements. In relaxed subjects,
      passive joint torque resistance at a given steady dorsiflexed position either
      gradually declined or rose depending on the direction of the previous transition
      movements. In corresponding voluntary contraction experiments, the IEMG amplitude
      from position holding wrist extensors was found to vary in a similar way as the
      passive torque resistance. Further, there was a strong correlation between
      history-dependent changes in extensor IEMG amplitude and stress alterations
      exhibited by the relaxed antagonist flexors. The above described, slowly
      subsiding post-movement mechanical and motor adaptations were accelerated by
      brief forceful cocontractions of the forearm muscles. CONCLUSION: Moderate
      stepwise changes in joint position are sufficient to induce history-dependent
      after-effects in passive muscular resting tension, after-effects which during
      voluntary position holding are effectively compensated for by the motor control
      system.

PMID- 15491409
TI  - Partial reversal of conduction slowing during repetitive stimulation of single
      sympathetic efferents in human skin.
AB  - AIMS: To describe and identify the function of a class of human C fibre with an
      unusual response to repetitive electrical stimulation. Other C fibres slow
      progressively at 2 Hz (type 1), reach a latency plateau (type 2) or hardly slow
      at all (type 3). METHODS: C fibres innervating hairy skin were recorded by
      microneurography in the superficial peroneal nerves of 19 healthy volunteers.
      Baseline electrical stimulation of the skin was at 0.25 Hz, and activity
      dependent slowing recorded during stimulation at 2 Hz for 3 min and after a 3-min
      pause in stimulation. RESULTS: In 41 units, there was a partial recovery of
      latency during repetitive stimulation. These were classified as 'type-4' units,
      and identified as sympathetic efferents, since they exhibited spontaneously
      activity, which was enhanced by manoeuvres that increase sympathetic outflow (15
      of 16 cases) and/or suppressed by a proximal anaesthetic block (eight of eight
      cases). The peak slowing during 2 Hz trains averaged 6.47 +/- 2.06% (mean +/- SD,
      n=41), but after 3 min the slowing had reduced to 4.90 +/- 2.20%, which was less
      than in all type 1 (nociceptor) fibres but similar to that in type 2 (cold)
      fibres. Compared with cold fibres, type-4 sympathetic fibres slowed more after
      the first 10 impulses at 2 Hz (2.57 +/- 0.45%) and also after a pause in
      stimulation (1.66 +/- 0.51%). CONCLUSIONS: The distinctive activity-dependent
      slowing profiles of these type-4 sympathetic C units may help identification in
      vitro, and suggest that hyperpolarization-activated channels have a particularly
      prominent role in the axonal membrane.

PMID- 15491410
TI  - Effect of exogenous angiotensin II on renal tissue nitric oxide and intrarenal
      circulation in anaesthetized rats.
AB  - AIM: The renal medullary circulation is protected against depressor action of
      angiotensin II (Ang II) because of the opposed action of a vasodilator agent,
      possibly nitric oxide (NO). This possibility was evaluated by a simultaneous
      determination of the effect of exogenous Ang II on renal cortical and medullary
      tissue NO and on intrarenal circulation. METHODS: In anaesthetized rats effects
      were determined of pressor and subpressor Ang II doses on tissue NO concentration
      in the renal cortex and inner medulla (selective NO electrodes), total renal
      blood flow (RBF, Transonic renal artery probe) and inner medullary blood flow
      (IMBF, laser Doppler flux). The measurements were repeated in rats treated with
      tempol, a scavenger of superoxide. RESULTS: Moderately pressor Ang II infusion
      significantly decreased tissue NO signal from 5.7 +/- 0.2 to 5.3 +/- 0.2 nA in
      the cortex and from 10.7 +/- 0.6 to 10.1 +/- 0.6 nA in the medulla. The RBF, a
      measure of cortical perfusion, decreased, and IMBF did not change. Subpressor
      doses of Ang II did not change medullary or cortical tissue NO. Tempol prevented
      an Ang II dependent decrease in medullary (but not cortical) NO without affecting
      RBF or IMBF responses. CONCLUSION: An absence of an increase in renal cortical or
      medullary tissue NO after infusion of subpressor or pressor doses of Ang II
      speaks against the role of this agent in buffering the intrarenal vasoconstrictor
      action of the hormone. Elimination of the post-Ang II decrease in medullary NO in
      animals pre-treated with tempol suggests that tissue superoxide generation
      stimulated by the hormone might reduce local bioavailability of NO.

PMID- 15491411
TI  - Update on the management of cutaneous lupus erythematosus.
AB  - This paper reviews the latest treatments for cutaneous lupus erythematosus. It
      focuses on evidence-based guidance for the management of cutaneous lupus
      erythematosus, with identification of the strength of evidence available at this
      time. In addition, I have briefly reviewed the epidemiological aspects, diagnosis
      and evaluation of patients with cutaneous lupus erythematosus. This review
      reflects data available from the Cochrane Library, Medline, literature searches,
      and the experience of the author managing patients with cutaneous lupus
      erythematosus for over 25 years.

PMID- 15491412
TI  - Differential expression of a human endogenous retrovirus E transmembrane envelope
      glycoprotein in normal, psoriatic and atopic dermatitis human skin.
AB  - BACKGROUND: Psoriasis is a common inflammatory skin disease characterized by
      uncontrolled proliferation of keratinocytes and recruitment of T lymphocytes into
      the skin. The possible role of human endogenous retroviruses (HERVs) in the
      induction of psoriasis has been suggested, based upon the previous observations
      of retrovirus-like particles in psoriasis from skin lesional plaques, urine and
      stimulated lymphocytes. OBJECTIVES: To investigate the expression of HERV-E
      transmembrane envelope glycoprotein (HERV-E env) in normal, psoriatic and atopic
      human skin, and to examine the influence of ultraviolet (UV) B irradiation on
      HERV-E env expression in normal human epidermal keratinocytes. METHODS: The
      analysis was performed on both skin biopsies and organotypic skin cultures using
      immunofluorescence and Western immunoblotting. UVB irradiation (312 nm) of
      cultured normal human keratinocytes was performed using a dose of 30 mJ cm(-2).
      RESULTS: Positive staining was observed in most of the psoriatic and atopic skin
      samples, whereas only 15% of the normal skin samples were faintly positive. In
      addition, the pattern of expression of HERV-E env differed markedly in psoriasis
      vs. atopy. By Western blotting analysis, two main proteins of 54 and 57 kDa were
      detected in extracts of normal skin, normal keratinocyte cultures and
      reconstructed epidermis from psoriatic and normal punch biopsies. An increased
      level of expression of these proteins was noted in extracts from psoriatic vs.
      normal reconstructed epidermis. The overexpression of the 57-kDa protein in
      normal human cultured keratinocytes was dramatically reduced by UVB irradiation.
      CONCLUSIONS: These data suggest for the first time that HERV-E env is expressed
      in normal and pathological human skin. Further studies are now required to
      elucidate the role of such viral proteins in the pathogenesis of psoriasis.

PMID- 15491413
TI  - Stratum corneum adhesive tape stripping: influence of anatomical site,
      application pressure, duration and removal.
AB  - BACKGROUND: Tape stripping is a common method for investigating stratum corneum
      (SC) physiology as well as bioavailability and bioequivalence of topical drugs.
      OBJECTIVES: To investigate the influence of procedures (anatomical site,
      pressure, pressure duration, tape removal rate) inherent in each stripping
      protocol on changes in skin physiology. METHODS: Tape stripping was performed
      using tapes on the forearm, forehead and back. On the forearm different pressures
      (165 and 330 g cm(-2)), durations of pressure (2 and 10 s), and removal rate
      (slow and rapid removal) were used. Changes in skin physiology were evaluated by
      measurement of transepidermal water loss (TEWL) and hydration. RESULTS: A
      significant influence of all parameters on the TEWL increase as a function of
      tape strip number was observed. The fastest increase was demonstrated on the
      forehead, followed by the back and, lastly, the forearm. Rapid removal produced a
      protracted increase in comparison with slow removal. Pressure for 10 s induced a
      faster increase in TEWL than 2 s pressure. Likewise, pressure at 330 g cm(-2)
      induced an earlier increase than pressure at 165 g cm(-2). Skin hydration was not
      influenced by the variables tested. CONCLUSIONS: Tape stripping results are
      influenced dramatically by all investigated parameters. A dynamic SC stress test
      to investigate SC cohesion more closely is proposed based on the present
      observations.

PMID- 15491414
TI  - Towards optimization of an organotypic assay system that imitates human hair
      follicle-like epithelial-mesenchymal interactions.
AB  - BACKGROUND: Human hair growth can currently be studied in vitro by the use of
      organ-cultured scalp hair follicles (HFs). However, simplified organotypic
      systems are needed for dissecting the underlying epithelial-mesenchymal
      interactions and as screening tools for candidate hair growth-modulatory agents.
      OBJECTIVES: To optimize the design and culture conditions of previously published
      organotypic systems that imitate epithelial-mesenchymal interactions in the human
      HF as closely as possible. MATERIALS AND METHODS: Continuous submerged
      organotypic 'sandwich' cultures were established. These consist of a pseudodermis
      (collagen I mixed with and contracted by human interfollicular dermal
      fibroblasts) on which one of two upper layers is placed: either a mixture of
      Matrigel basement membrane matrix (BD Biosciences, Bedford, MA, U.S.A.) and
      follicular dermal papilla fibroblasts (DPC), with outer root sheath keratinocytes
      (ORSK) layered on the top ('layered' system), or a mixture of Matrigel, DPC and
      ORSK ('mixed' system). Morphological and functional characteristics of these
      'folliculoid sandwiches' were then assessed by routine histology,
      histomorphometry and immunohistochemistry. RESULTS: In both 'layered' and 'mixed'
      systems, the ORSK formed spheroid epithelial cell aggregates, which retained
      their characteristic keratin expression pattern (i.e. cytokeratin 6). In the
      'mixed' sandwich model the size of the epithelial cell aggregates was smaller,
      but the numbers of ORSK were significantly higher than in the 'layered' model at
      day 14 in the culture. ORSK proliferated better in the 'mixed' than in the
      'layered' sandwich system, regardless of the calcium or serum content of the
      media, whereas apoptosis of ORSK was lowest in the 'mixed' system in serum-free,
      low calcium medium. The kinetics of proliferation and apoptosis of DPC, which
      retained their characteristic expression of versican, were similar in both
      systems. However, proliferation and apoptosis of DPC were higher in the presence
      of serum and/or under high calcium conditions. CONCLUSIONS: Our results
      underscore the importance of structural design and medium composition for
      epithelial-mesenchymal interactions as they occur in the human HF. Specifically,
      we report a new organotypic submerged 'folliculoid sandwich' system with serum
      free, low calcium medium and a mixture of interacting human DPC and ORSK, which
      offers several advantages over previously available assays. This system allows
      the standardized assessment of the effects of a test agent on the proliferation,
      apoptosis and key marker expression of human ORSK and DPC under substantially
      simplified in vitro conditions which approximate the in vivo situation.

PMID- 15491415
TI  - Peroxisome proliferator-activated receptor and farnesoid X receptor ligands
      differentially regulate sebaceous differentiation in human sebaceous gland organ
      cultures in vitro.
AB  - BACKGROUND: Nuclear hormone receptors are important in the regulation of
      epidermal differentiation and have been implicated in lipid metabolism. In
      particular, there is evidence suggesting that the activation of peroxisome
      proliferator-activated receptors (PPARs) is an important factor in the regulation
      of sebocyte lipogenesis. OBJECTIVES: To determine the role of PPARs, farnesoid X
      receptor (FXR) and other orphan nuclear hormone receptors in sebaceous gland
      function in vitro by investigating the biochemical effects of appropriate
      ligands, and by establishing the RNA and protein expression patterns of a number
      of nuclear receptors in sebaceous glands ex vivo. METHODS: Human chest sebaceous
      glands were maintained in vitro as freshly isolated and as 7-day cultured whole
      organs. We then studied the effects of appropriate ligands on the glandular rates
      of lipogenesis and DNA synthesis, as well as determining the mRNA (reverse
      transcription-polymerase chain reaction) and protein expression patterns
      (immunohistochemistry/immunoblotting) of the nuclear hormone receptors of
      interest. RESULTS: PPAR ligands, but not FXR ligands, inhibited sebaceous
      lipogenesis, in particular the PPARalpha ligands LY 171883 and WY 14643, and the
      PPARgamma ligands BRL 49653 and 15-deoxy-Delta-12,14-prostaglandin J(2). We
      detected RNA expression of PPARalpha, PPARbeta, PPARgamma, retinoid X receptor
      alpha, liver X receptor alpha (LXRalpha) and pregnane X receptor but not FXR in
      freshly isolated and 7-day maintained sebaceous glands. PPARalpha, PPARbeta,
      PPARgamma and LXRalpha protein were detected in nuclear extracts of sebaceous
      glands. CONCLUSIONS: We conclude that activation of nuclear hormone receptors, in
      particular activation of PPARalpha and PPARgamma, can regulate lipogenesis in
      human sebaceous glands. As suppression of sebum secretion is associated with
      reduced acne activity, the nuclear hormone receptors involved may open new
      avenues in the development of novel acne treatments.

PMID- 15491416
TI  - Keratinocyte-derived cytokines after photodynamic therapy and their paracrine
      induction of matrix metalloproteinases in fibroblasts.
AB  - BACKGROUND: Recent studies have shown that collagen-degrading matrix
      metalloproteinase (MMP)-1 and MMP-3 are produced by fibroblasts in response to
      photodynamic therapy (PDT) with 5-aminolaevulinic acid (ALA) and are considered
      to be involved in the antisclerotic effects of ALA-PDT observed in the treatment
      of localized scleroderma. OBJECTIVES: As the primary target of topical PDT is
      epidermal keratinocytes, we studied the indirect participation of keratinocytes
      in the production of MMPs and collagen by dermal fibroblasts. METHODS:
      Keratinocytes were treated with sublethal doses of ALA (100 micromol L(-1)) and
      red light. The conditioned media were collected 24 h after PDT and primary human
      fibroblasts were exposed to these media for 6-48 h. Further, a coculture model,
      keratinocytes seeded on to collagen type IV-coated transwells in the upper
      chamber and fibroblasts in the lower chamber, was used to study paracrine effects
      of keratinocytes after PDT. RESULTS: Keratinocyte supernatants after PDT showed a
      significant, up to 10-fold increase of interleukin (IL)-1alpha and a 2.5-fold
      increase of tumour necrosis factor-alpha as determined by enzyme-linked
      immunosorbent assay, while IL-6, MMP-1 and MMP-3 were not altered significantly.
      Fibroblasts treated with keratinocyte-conditioned media after PDT showed an
      induction of MMP-1 and MMP-3 protein levels up to threefold in both models used,
      suggesting that ALA-PDT modulates MMP-1 and MMP-3 production via indirect
      mechanisms. Collagen type I mRNA expression by fibroblasts was not altered
      significantly in either model. The addition of an IL-1 receptor antagonist to the
      keratinocyte-conditioned media completely inhibited the induction of MMP-1 and
      MMP-3 in stimulated fibroblasts, suggesting that IL-1 is mainly responsible for
      the observed paracrine effects. CONCLUSIONS: We present evidence that PDT can
      trigger MMP production in dermal fibroblasts not only directly as has been
      already shown, but also by an indirect paracrine loop mediated by soluble factors
      released by epidermal keratinocytes.

PMID- 15491417
TI  - Infiltrating cells, related cytokines and chemokine receptors in lesional skin of
      patients with dermatomyositis.
AB  - BACKGROUND: There have been only two reports on immunophenotypic characterization
      in the cutaneous lesions of dermatomyositis (DM) that emphasize the importance of
      the infiltrating CD4+ T lymphocytes. OBJECTIVES: To characterize the
      immunophenotype of the cells that infiltrate the lesional skin of DM and to
      evaluate the possible T-helper (Th) polarization Th1/Th2 through detection of
      specific cytokines, chemokine receptors and markers of cellular activation.
      METHODS: Skin biopsy specimens derived from pathognomonic lesions (Gottron's
      papules and Gottron's sign) of eight patients with DM were immunostained with a
      large panel of monoclonal antibodies to CD3, CD4, CD8, myeloperoxidase (MPO),
      eosinophil cationic protein, tryptase, CD40, CD40 ligand (CD40L), HLA-DR,
      interleukin (IL)-2, IL-4, IL-5, IL-13, interferon-gamma, tumour necrosis factor
      alpha, receptor 3 for CXC chemokines (CXCR3) and receptor 3 for CC chemokines,
      using the alkaline phosphatase-antialkaline phosphatase method. Control specimens
      were obtained from five healthy subjects and from six patients with discoid lupus
      erythematosus. RESULTS: Activated CD4+ Th lymphocytes (HLA-DR+ CD40L+) were the
      principal infiltrating cells in the lesional skin of DM; the CD4/CD8 ratio was
      approximately 2.5. A mixed Th1/Th2 profile and higher Th1 cytokine production
      together with significant staining for CXCR3 were detected. Neutrophil
      granulocytes were the second most abundant population; eosinophil granulocytes
      were very poorly represented. CONCLUSIONS: Activated CD4+ T cells presumably
      mediate the main pathogenetic mechanisms in pathognomonic skin lesions. The
      interaction between CD40 and CD40L could be an important mechanism of cellular
      activation in cutaneous immune-mediated inflammation by induction of secretion of
      proinflammatory cytokines and chemokines. Neither Th1 nor Th2 clear polarization
      was found, although there was a slight Th1 prevalence. There was a significant
      quantity of MPO+ cells (neutrophil granulocytes) in the inflamed tissue, and they
      might have a role in sustaining the chronic inflammation.

PMID- 15491418
TI  - Association of insertion/deletion polymorphism of the angiotensin-converting
      enzyme gene with psoriasis.
AB  - BACKGROUND: Genetic factors are likely to be of fundamental importance in the
      pathogenesis of psoriasis. There are reports concerning the induction or/and
      exacerbation of psoriasis by angiotensin-converting enzyme (ACE) inhibitors,
      which have been attributed to the ACE inhibitor-induced augmentation of kinin
      levels in skin. However, to the best of our knowledge there has been no molecular
      genetic study investigating whether ACE insertion/deletion (I/D) polymorphism may
      contribute to the genetic background in psoriasis. OBJECTIVES: To assess the role
      of ACE I/D polymorphism in psoriasis. METHODS: A group of 86 patients with
      psoriasis and 154 control subjects were analysed for ACE I/D polymorphism by
      polymerase chain reaction. RESULTS: The distribution of ACE I/D polymorphism and
      allele frequencies in psoriatic patients was not significantly different from
      controls. Further analyses of psoriasis patients showed that ACE I/D polymorphism
      was not associated with age at onset of disease, clinical type of psoriasis or
      gender. However, the frequency of the I allele was significantly higher in
      patients with a positive family history of psoriasis than in those with no family
      history (sporadic psoriasis) (48% vs. 32%; P =0.03). In addition, the I allele
      was found significantly more frequently in type I psoriasis patients (onset < 40
      years and positive family history) than in type II psoriasis patients (onset >/=
      40 years, no family history) (48% vs. 27%; P = 0.04). CONCLUSIONS: Our results
      suggest that the presence of the I allele may confer susceptibility to
      development of psoriasis in individuals from psoriatic families.

PMID- 15491419
TI  - Intracellular degradation of beta4 integrin in lethal junctional epidermolysis
      bullosa with pyloric atresia.
AB  - BACKGROUND: Junctional epidermolysis bullosa with pyloric atresia (PA-JEB) is a
      rare autosomal recessive genodermatosis that manifests with neonatal
      mucocutaneous blistering and gastric outlet obstruction. The disease, which is
      caused by mutations in the alpha6beta4 integrin genes (ITGA6, ITGB4), is usually
      lethal. However, nonlethal cases have also been reported. Mutation database
      analysis has suggested that premature termination codons predominantly result in
      lethal forms while missense mutations frequently associate with nonlethal
      variants. Nevertheless, it is becoming more and more evident that the disease
      phenotype is also influenced by the position of the mutation in the protein
      functional domains. OBJECTIVE: To investigate the molecular basis of a novel PA
      JEB lethal case. METHODS: Reverse transcriptase-polymerase chain reaction and
      direct sequencing-based mutation screening were performed. Mutation consequences
      in the patient's keratinocytes were then analysed by Northern blot and
      immunoprecipitation. Immunofluorescence analysis of cultured keratinocytes
      treated with protein intracellular degradation pathway inhibitors was also
      carried out. RESULTS: The phenotype was caused by the presence, in the homozygous
      state, of a novel 33 bp in-frame deletion (nucleotides 175-207) in the ITGB4
      coding sequence. Despite the normal steady-state level of integrin beta4 mRNA,
      the mutation, designated DeltaR59-A69, results in the almost complete absence of
      alpha6beta4 integrin in the patient's skin and cultured keratinocytes. Exposure
      of the patient's keratinocytes to the proteasomal inhibitor clasto-lactacystin
      beta-lactone increased the expression of the mutated beta4 integrin chains
      indicating that the proteasome complex is involved in the degradation of the
      internally deleted beta4 polypeptides. CONCLUSIONS: We report for the first time
      a homozygous in-frame deletion in the ITGB4 gene. Our results suggest that the
      deletion of amino acids R59-A69 interferes with the biosynthetic folding of the
      protein, leading to a rapid degradation of the mutated beta4 chains. These
      findings provide new insight into the pathogenic effects of mutations affecting
      different functional domains of the beta4 integrin molecule and their prognostic
      implications in PA-JEB patients.

PMID- 15491420
TI  - Rheumatoid factor isotypes and anti-agalactosyl IgG antibodies in systemic
      sclerosis.
AB  - BACKGROUND: Rheumatoid factor isotypes and anti-agalactosyl IgG antibodies (anti
      AG IgG) have been reported to be detected and correlated with the disease
      activity in some collagen diseases. OBJECTIVES: To study the frequency and the
      clinical significance of IgM, IgG and IgA rheumatoid factor (IgM-RF, IgG-RF and
      IgA-RF) and anti-AG IgG in patients with systemic sclerosis (SSc). METHODS:
      Seventy-nine serum samples from patients with SSc were examined by specific
      enzyme-linked immunosorbent assays. RESULTS: The levels of IgM-, IgG-, IgA-RF and
      anti-AG IgG were significantly higher in SSc patients than in normal healthy
      controls. The levels of IgM- and IgA-RF were significantly higher in patients
      with diffuse cutaneous SSc than in those with limited cutaneous SSc. IgM-, IgG-
      and IgA-RF and anti-AG IgG were significantly elevated in 39%, 32%, 23% and 35%
      of 79 SSc patients, respectively. The prevalence of pulmonary fibrosis,
      oesophageal involvement and cutaneous telangectasias in patients with elevated
      IgA-RF levels was significantly higher than in those with normal levels. The
      incidence of pitting scars of digits in those with elevated IgG-RF levels and the
      incidence of contracture of phalanges in those with elevated IgM-RF levels were
      significantly higher than in those with normal levels. The frequency of increased
      erythrocyte sedimentation rate in patients with elevated IgG-RF and the frequency
      of increased C-reactive protein in those with elevated IgM-RF were significantly
      greater than in those with normal levels. CONCLUSIONS: IgM-, IgG-, IgA-RF and
      anti-AG IgG can be serum indicators of specific clinical manifestations in SSc
      patients.

PMID- 15491421
TI  - Combined in vivo and in vitro approach for the characterization of penicillin
      specific polyclonal lymphocyte reactivity: tolerance tests with safe penicillins
      instead of challenge with culprit drugs.
AB  - BACKGROUND: Amino-penicillins are a major cause of delayed-type reactions to
      penicillins. OBJECTIVES: The aim of this study was to establish a diagnostic
      approach for the characterization of the individual penicillin-specific
      polyclonal lymphocyte reactivity in order to detect side chain-specific
      sensitization to amino-penicillins. Patients can then be advised to undergo a
      tolerance test with safe penicillins instead of provocation with culprit
      penicillins for confirmation of penicillin allergy. METHODS: We investigated
      penicillin-specific polyclonal lymphocyte reactivity in nine patients with
      delayed-type reactions to amino-penicillins by a combined in vivo (patch, prick
      and intracutaneous tests with delayed readings) and in vitro (lymphocyte
      transformation test, LTT) approach. RESULTS: A combination of LTT and skin tests
      improved the sensitivity for the characterization of penicillin-specific
      polyclonal lymphocyte reactivity and allowed the detection of three different
      patterns of lymphocyte reactivity. Four patients showed a side chain-specific
      sensitization to amino-penicillins in vivo and in vitro and were advised to
      undergo tolerance tests with safe penicillins. Two patients agreed and were
      exposed to parenteral benzyl-penicillin and oral phenoxymethyl-penicillin which
      they tolerated without complications. CONCLUSIONS: These data suggest that a
      combined in vivo and in vitro approach is helpful for the detection of side chain
      specific sensitization to amino-penicillins. Patients with such sensitization are
      very likely to tolerate safe penicillins, thereby expanding their therapeutic
      options when antibiotic treatment is required.

PMID- 15491422
TI  - Methyldibromoglutaronitrile in leave-on products elicits contact allergy at low
      concentration.
AB  - BACKGROUND: The rapidly increasing level of contact allergy to
      methyldibromoglutaronitrile (MDBGN) in Europe is of concern. In April 2003, the
      EU Commission prohibited the use of MDBGN in leave-on cosmetic products, such as
      creams and lotions, until a level of safe use can be defined. Industry risk
      assessment has indicated that such a safe level could be 50-100 p.p.m.
      OBJECTIVES: To determine whether 50 p.p.m. or 100 p.p.m. could be tolerated by
      MDBGN-sensitized individuals, and to evaluate if the risk for elicitation of
      MDBGN allergy is higher for a leave-on product with a high lipid content than for
      a product with a low lipid content. METHODS: Eighteen volunteers with contact
      allergy to MDBGN and 10 healthy controls were exposed to repeated open
      application tests (ROATs) with two moisturizers with a high and a low lipid
      content, respectively, both containing MDBGN at a concentration of 50 p.p.m. The
      ROATs were performed on the left and the right side of the neck for 14 days, or
      until a positive reaction was seen. If a positive reaction did not develop within
      the first 14 days, two analogous moisturizers containing 100 p.p.m. MDBGN were
      applied for a further 14 days. Clinical assessments were done on days 2, 3, 7,
      14, 21 and 28 or when a reaction developed. RESULTS: Eleven of 18 (61%) subjects
      developed dermatitis on the test area, of whom 10 developed a positive reaction
      to the 50 p.p.m. moisturizer, seven having a positive reaction on day 2 or 3.
      Reactions to the low-lipid moisturizer were the more frequent. All participants
      used more of the low-lipid moisturizer than the high-lipid moisturizer. The
      controls all had negative ROATs. CONCLUSIONS: Even 50 p.p.m. cannot be regarded
      as a safe concentration for use and the prohibition of MDBGN is scientifically
      well founded.

PMID- 15491423
TI  - TARC and RANTES, but not CTACK, are induced in two models of allergic contact
      dermatitis. Effects of cilomilast and diflorasone diacetate on T-cell-attracting
      chemokines.
AB  - BACKGROUND: Skin-infiltrating T cells play a predominant role in allergic and
      inflammatory skin diseases such as atopic dermatitis and allergic contact
      dermatitis. These T cells are attracted by chemotactic factors, e.g. RANTES
      (regulation on activation, normal T cell expressed and secreted; CCL5), TARC
      (thymus and activation regulated chemokine; CCL17) and CTACK (cutaneous T-cell
      attracting chemokine; CCL27). OBJECTIVES: To investigate which T-cell-attracting
      chemokines are involved in allergic contact dermatitis in mice. METHODS: Allergic
      contact dermatitis was induced by application of dinitrochlorobenzene (DNCB) or
      toluene-2,4-diisocyanate (TDI), and chemokine concentrations were determined by
      enzyme-linked immunosorbent assay. The effects on chemokine concentrations of the
      highly selective phosphodiesterase 4 inhibitor cilomilast and the glucocorticoid
      diflorasone diacetate were studied in mouse ears. RESULTS: RANTES and TARC were
      elevated in both models of allergic contact dermatitis 24 h after challenge,
      whereas CTACK remained unchanged. The increase in RANTES was diminished in mouse
      ears pretreated with cilomilast or diflorasone diacetate. TARC was reduced by
      diflorasone diacetate in the DNCB model but was highly induced in the TDI model;
      in contrast, TARC was not influenced by cilomilast. CONCLUSIONS: TARC and RANTES,
      but not CTACK, are involved in these two models of allergic contact dermatitis.

PMID- 15491424
TI  - Perforin expression is upregulated in the epidermis of psoriatic lesions.
AB  - BACKGROUND: There are currently very few data regarding the role of cell-mediated
      cytotoxicity in psoriasis. Both cytotoxic T lymphocytes and natural killer (NK)
      cells mediate cytotoxicity reactions, mainly by two distinct pathways, the
      perforin/granzyme and the Fas/Fas ligand pathway. OBJECTIVES: To study the
      expression and distribution of perforin, T- and NK-cell subsets in psoriatic
      lesional and nonlesional skin. METHODS: Skin biopsy specimens from both lesional
      and nonlesional skin of 11 patients with chronic plaque psoriasis and eight
      healthy controls were analysed by immunohistochemistry. RESULTS: We found a
      significant increase in CD4+ and CD8+ cells in psoriatic lesions compared with
      nonlesional and healthy skin. The expression of CD16+ NK cells was significantly
      lower in lesions compared with healthy skin. Perforin expression was
      significantly enhanced in the epidermis of psoriatic lesions. CONCLUSIONS:
      Perforin expression is upregulated in the epidermis of psoriatic lesions,
      suggesting a potential role for perforin in the creation of the psoriatic plaque.

PMID- 15491425
TI  - Cyclooxygenase-2 expression and angiogenesis in squamous cell carcinoma of the
      skin and its precursors: a paired immunohistochemical study of 35 cases.
AB  - BACKGROUND: Cyclooxygenase (COX)-2 expression and tumour-induced angiogenesis
      appear to be increased in squamous cell carcinoma (SCC) of the skin. In other
      cancers, COX-2 is a pro-angiogenic factor. The association between angiogenesis
      and COX-2 has not been studied in skin cancer. OBJECTIVES: To assess the onset of
      increased COX-2 expression and angiogenesis in the multistage carcinogenesis of
      SCC as well as the correlation between those two parameters. PATIENTS/METHODS: We
      performed a retrospective paired immunohistochemical analysis of normal skin,
      actinic keratosis (AK), Bowen's disease (BD) and SCC among 35 individuals.
      Specimens were considered COX-2 immunopositive when 5% or more of the tumour
      cells showed clear evidence of immunostaining. To quantify active angiogenesis,
      we used a Ki-67-CD34 double-labelling immunohistochemical stain and calculated
      the fraction of proliferating endothelial cells. The Chalkley method was used to
      determine the microvessel density. To detect hypoxia, a carboanhydrase IX
      immunostain was used. RESULTS: Compared with normal epidermis (0%), AK (31%), BD
      (22%) and SCC (40%) were significantly more likely to be COX-2 immunopositive (P
      < 0.01). The fraction of proliferating endothelial cells and the Chalkley scores
      paralleled multistage carcinogenesis (P < 0.05 between different stages). COX-2
      immunopositivity was fairly correlated with hypoxia and higher proliferating
      endothelial cell fractions but not with Chalkley counts. CONCLUSIONS: Induction
      of COX-2 expression and angiogenesis are both early events in the development of
      SCC. In addition to ultraviolet light, hypoxia and COX-2 may be involved in skin
      tumour angiogenesis.

PMID- 15491426
TI  - Expression of the peripheral benzodiazepine receptor is decreased in skin cancers
      in comparison with normal skin.
AB  - BACKGROUND: The peripheral benzodiazepine receptor (PBR) is an 18-kDa protein
      receptor mainly found on the outer mitochondrial membrane of cells. The PBR plays
      a role in several cellular functions including haem synthesis, steroidogenesis,
      DNA synthesis, cell growth and differentiation, and apoptosis. PBR expression in
      normal skin correlates with proliferating, secretory and differentiated cellular
      structures. Increased or aberrant expression of PBR has been associated with
      aggressive behaviour in several tumour types including ovarian, colon and breast
      adenocarcinomas and glioblastoma. OBJECTIVES: To determine whether changes in
      normal PBR distribution would be useful as markers for skin cancers or possible
      target sites for therapies such as photodynamic therapy (PDT), we used
      immunohistochemistry to evaluate PBR expression and distribution in normal and
      photodamaged skin (actinic keratoses), skin cancers (in situ and invasive
      squamous cell carcinomas and superficial, nodular, morphoeiform and mixed pattern
      basal cell carcinomas) and several benign epithelial proliferations. METHODS: A
      rabbit polyclonal antibody to a synthetic peptide fragment of the PBR was
      developed and characterized by enzyme-linked immunosorbent assay and Western blot
      analysis. The antibody was used to stain formalin-fixed and paraffin-embedded
      tissue samples (n = 157) by a routine avidin-biotin immunohistochemical
      technique. Sections were evaluated for antibody localization, distribution (0-4+)
      and reaction intensity (negative to strong). RESULTS: Normal skin stained with a
      strong homogeneous positive reaction (3-4+) in the spinous and granular layers
      (with a gradient corresponding to increasing differentiation), the pilosebaceous
      units, eccrine gland ducts, endothelial cells and pilar muscle. In cutaneous
      neoplasms and other skin diseases, a heterogeneous pattern (0-4+) of PBR
      expression at lower intensity was seen depending on tumour type and degree of
      differentiation. PBR expression was greatest in well-differentiated tumours,
      synonymous with the PBR expression gradient seen in normal skin; and least in
      poorly differentiated and infiltrative tumour types. CONCLUSIONS: The haem
      biosynthetic pathway has been harnessed for PDT of skin carcinomas by application
      of exogenous aminolaevulinic acid to generate the endogenous photosensitizer
      protoporphyrin IX (PpIX). Owing to the role of PBR as a transporter of haem
      precursors in haem synthesis, PBR density and distribution in skin cancers could
      be a predictor of the capacity for PpIX production and subsequent response to PDT
      in skin cancers.

PMID- 15491427
TI  - Implementation of a leg ulcer strategy.
AB  - BACKGROUND: The care of patients with leg ulceration has developed over the past
      15 years, although there is little information available to determine how these
      changes have affected clinical and patient defined outcomes. OBJECTIVES: To
      describe and evaluate the implementation of a leg ulcer strategy.
      PATIENTS/METHODS: This study used a pre- and postimplementation evaluation within
      population-based services within the boundaries of community services providing
      leg ulcer care. Evidence-based leg ulcer services were developed, including
      standardized assessment using Doppler ultrasound, rationalization of treatment
      using multilayer elastic high compression, development of referral criteria and
      acute service support. Complete ulcer healing rates, health-related quality of
      life and use of health resources were evaluated after 12 weeks in both pre- and
      postimplementation cycles. RESULTS: A total of 955 patients were evaluated (518
      preimplementation, 437 postimplementation). The levels of assessment and
      treatment were poor prior to the change in practice with just one patient having
      evidence of correct assessment and 49 (11%) receiving high compression therapy.
      Postimplementation, this improved to 412 of 437 (94%) having evidence of
      measurement of the ankle brachial pressure index, and 85% receiving compression.
      Twelve-week healing rates preimplementation ranged between 9% and 24%, and
      postimplementation rose from 19% to 39%. Combined overall healing rates improved
      from 71 of 518 (14%) to 160 of 437 (37%), odds ratio =3.53, P < 0.001. Frequency
      of treatment visits reduced from a mean (SD) of 24.0 (16.1) over 12 weeks to 13.5
      (8.6), P < 0.001. Intervention led to major improvements in health-related
      quality of life (measured using the Nottingham Health Profile), with significant
      improvements for energy, pain, sleep and mobility (P < 0.01). CONCLUSIONS:
      Rationalization of leg ulcer services through a total service change results in
      improvements in professional practice, better patient outcomes, and efficient use
      of current resources. This study highlights the importance of a multifaceted
      approach to improve practice focused on the needs of individual organizational
      settings.

PMID- 15491428
TI  - The future incidence of cutaneous melanoma within the UK.
AB  - BACKGROUND: The incidence of cutaneous malignant melanoma continues to rise in
      the U.K., where since the 1970s malignant melanoma has seen the largest increase
      in incidence rates compared with other major cancers. To counteract this rise,
      sun awareness campaigns have been introduced in this and several other countries
      since the 1980s with the object of encouraging people to limit their exposure to
      strong sunshine and to avoid sunburn in the expectation that these interventions
      will act favourably on skin cancer incidence. OBJECTIVES: To predict the
      incidence of cutaneous malignant melanoma in the British population over the next
      half-century as a consequence of either a stabilization or a reduction in
      lifetime risk of melanoma for recent and future birth cohorts so that cancer
      services can be planned appropriately over the coming years. METHODS: An age
      cohort model has been developed that estimates future incidence rates of melanoma
      in the U.K. RESULTS: The results suggest that the benefits of intervention
      strategies, assuming that these will translate eventually into a downturn in
      melanoma incidence, may not be seen for another 30 years or so, by which time the
      predicted age-standardized rate of melanoma may be around twice that presently
      observed. CONCLUSIONS: Prevention of deaths from melanoma depends on both
      reducing incidence and achieving earlier diagnosis. This analysis has indicated
      that the former is unlikely to be realized in the U.K. for some decades, and so
      early detection of suspected lesions, with prompt surgery to remove confirmed
      tumours, is paramount if mortality from melanoma is to be kept in check.

PMID- 15491429
TI  - Implication for photosensitive patients of ultraviolet A exposure in vehicles.
AB  - BACKGROUND: Photosensitive patients sometimes report disease flares during
      journeys by car. Window glass blocks all UVB but not all UVA. All car windscreens
      are made from laminated glass. Side and rear windows are usually made of
      nonlaminated glass. OBJECTIVES: To determine which types of glass provide most
      protection from UVA with particular reference to the implications for patients
      with polymorphic light eruption (PLE). METHODS: The percentage transmission of
      UVA was determined for a selection of glass, both laminated and nonlaminated, and
      with differing colour tints. RESULTS: Laminated glass transmits less UVA than
      nonlaminated glass. Tinted glass transmits less UVA than clear glass.
      Nonlaminated clear glass transmitted the highest percentage of UVA (62.8%) and
      grey laminated glass the lowest (0.9%). A dose of 5 J cm(-2) UVA, enough to
      trigger PLE in some patients, could be transmitted through clear nonlaminated
      glass in 30 min but would take 50 h through grey laminated glass. CONCLUSION:
      Patients with severe UVA-induced PLE and other photosensitivity disorders may
      have disease flares from solar UVA transmission through side-window glass.
      Protective measures such as wearing long-sleeved clothing, keeping the arm
      beneath the bottom of the window aperture, or choosing tinted and laminated car
      windows may be helpful.

PMID- 15491430
TI  - Efficacy of monochromatic excimer laser radiation (308 nm) in the treatment of
      early stage mycosis fungoides.
AB  - BACKGROUND: Various reports have recently shown the efficacy of narrowband
      ultraviolet (UV) B phototherapy at 311 nm in the treatment of early stage mycosis
      fungoides (MF). OBJECTIVES: To examine the effectiveness and tolerability of
      monochromatic excimer light (MEL) at 308 nm as a first treatment for early stage
      MF (stage IA). METHODS: Ten lesions from five patients with a clinical and
      histological diagnosis of MF were treated with repeated applications of MEL until
      complete remission was achieved or up to a maximum of 10 applications, with a
      cumulative dose of 308 nm UVB of between 6 and 12 J cm(-2). All patients were
      observed every 2 weeks for 2 months, with a 1-year follow-up. Results At present,
      all patients are in complete remission, with no side-effects. CONCLUSIONS: Based
      on these results, MEL can be considered a useful tool in the treatment of early
      stage MF.

PMID- 15491431
TI  - Topical 5-aminolaevulinic acid-photodynamic therapy for the treatment of urethral
      condylomata acuminata.
AB  - BACKGROUND: Electrocoagulation and laser evaporation for urethral condylomata
      acuminata have high recurrence rates and can be associated with urethral
      malformations. OBJECTIVES: To investigate the effect of photodynamic therapy
      (PDT) with topical 5-aminolaevulinic acid (ALA) on urethral condylomata acuminata
      and to examine the histological changes in lesions of condylomata acuminata after
      ALA-PDT. METHODS: Patients with urethral condylomata (n = 164) were given topical
      ALA followed by intraurethral PDT through a cylindrical fibre. Patients included
      11 individuals with 16 penile or vulval condylomatous lesions which were biopsied
      before or after treatment; the histological changes were then evaluated by light
      microscopy and electron microscopy. RESULTS: The complete response rate was 95%
      and the recurrence rate was 5% after 6-24 months of follow-up. Light microscopy
      revealed keratinocytes in the middle and upper layers of the epidermis showing
      marked vacuolation and some necrocytosis 1 and 3 h after PDT. Necrosis in all
      layers of the epidermis was noted 5 h after PDT. Electron microscopy of
      keratinocytes revealed distinct ultrastructural abnormalities of mitochondria and
      the endoplasmic reticulum, and membrane damage. Apoptotic bodies were detected 3
      h after PDT and a large number of keratinocytes exhibited necrosis 5 h after PDT.
      CONCLUSIONS: Results suggest that, compared with conventional therapies, topical
      ALA-PDT is a simple, effective, safe and well-tolerated treatment for urethral
      condylomata acuminata that is associated with a low recurrence rate. The
      mechanism might be the triggering of both apoptosis and necrosis by ALA-PDT in
      human papillomavirus-infected keratinocytes.

PMID- 15491432
TI  - Tinea capitis in infants in their first year of life.
AB  - BACKGROUND: Tinea capitis is the most common type of dermatophytosis in children,
      but is uncommon in the first year of life. OBJECTIVES: To review clinical,
      mycological and epidemiological data in a series of 10 infants aged under 1 year
      diagnosed as having tinea capitis in three Spanish hospitals between 1998 and
      2002. METHODS: A retrospective case note study. RESULTS: There were six boys and
      four girls with a mean of age 7 months (range 1.5-12). All the children were born
      in Spain, but in five cases the parents were immigrants from Africa. In these
      cases the isolated dermatophytes were two Trichophyton tonsurans, one T.
      verrucosum and two Microsporum audouinii. Four autochthonous cases were caused by
      M. canis and one by M. audouinii (but this one was in contact with African
      immigrants). In two of the five cases produced by anthropophilic dermatophytes
      other family members were infected by the same fungus. Most cases were treated
      successfully with griseofulvin. CONCLUSIONS: Although tinea capitis is rare in
      infants in their first year of life, the condition should be investigated if
      scaling and/or alopecia are present. A thorough epidemiological study of other
      family members is mandatory.

PMID- 15491433
TI  - Coeliac disease-associated antibodies correlate with psoriasis activity.
AB  - BACKGROUND: Antigliadin antibodies (AGA) have been reported in patients with
      psoriasis. OBJECTIVES: To determine if AGA and other coeliac disease (CD)
      associated antibodies correlate with clinical features and activity in patients
      with psoriasis. METHODS: Patients with psoriasis (n = 130) were investigated for
      serum IgG and IgA AGA, IgA antitransglutaminase antibody and IgA antiendomysial
      antibody. Disease characteristics and associated bowel and joint symptoms were
      determined. All patients were invited to undertake endoscopy with duodenal
      biopsy. RESULTS: A significantly higher proportion of patients with elevated CD
      associated antibody levels was currently on or had previously required systemic
      immunosuppressants (methotrexate, ciclosporin or etretinate; P = 0.04) or
      psoralen plus ultraviolet A phototherapy (P = 0.03). One case of CD was
      diagnosed. CONCLUSIONS: The presence of CD-associated antibodies in psoriasis
      patients correlates with greater disease activity.

PMID- 15491434
TI  - Better medication adherence results in greater improvement in severity of
      psoriasis.
AB  - BACKGROUND: Patients are commonly nonadherent to medication regimens. In
      dermatology, there has been little study of the effect of nonadherence on
      outcomes. OBJECTIVES: To test the association between adherence behaviour and
      changes in severity of psoriasis. METHODS: Twenty-four subjects with psoriasis
      were enrolled in an 8-week, left/right, controlled trial of salicylic acid plus
      topical tacrolimus ointment vs. salicylic acid plus placebo. Subjects were given
      salicylic acid to apply to all lesions. The salicylic acid was supplied in a
      bottle with a medication event monitoring system cap in order to assess adherence
      to the salicylic acid. The primary outcome for this study was the relationship
      between the change in the disease severity (change in sum score of erythema,
      scale and thickness scores for a target plaque) and medication adherence.
      RESULTS: The mean initial disease severity was 5.8 on a nine-point sum score
      scale. For the topical tacrolimus-treated side, a decrease in adherence rate of
      10% was associated with a 1-point increase in severity (P < 0.05). For the
      placebo-treated side, adherence was not significantly correlated with changes in
      severity. CONCLUSIONS: Nonadherence may have a significant role in altering
      clinical trial data, skewing it towards ineffectiveness. Improved outcomes in
      psoriasis may be achievable through interventions that improve patients'
      adherence to treatment.

PMID- 15491435
TI  - Sodium benzoate-induced repeated episodes of acute urticaria/angio-oedema:
      randomized controlled trial.
AB  - BACKGROUND: Sodium benzoate (E 211) is widely used to delay yeast spoilage of
      acidic foods and beverages. Numerous cases of adverse reactions to benzoate have
      been recorded, but most of the studies that have been conducted lacked proper
      placebo controls or blinding. OBJECTIVE: The aim of this study is to determine
      the incidence of intolerance to sodium benzoate among subjects who experienced
      repeated episodes of acute urticaria/angio-oedema following the ingestion of a
      meal or a product containing this substance. METHODS: This was a retrospective
      study based on the analysis of data from patients reported to have experienced
      episodes of urticaria, with or without angio-oedema, after ingesting meals or
      products containing sodium benzoate. At the first visit to the outpatients
      clinic, a careful history was taken. Patients were then given the following
      diagnostic tests: tests for IgE for common inhalant allergens and food allergens,
      and a double-blind, placebo-controlled challenge with sodium benzoate. RESULTS: A
      total of 47 subjects were enrolled in the study; five (11%) showed at least one
      relevant positive reaction to an IgE test for food allergy. Only one subject (2%)
      had a reaction after the ingestion of 75 mg of sodium benzoate without an adverse
      reaction to placebo. CONCLUSION: This study shows that the percentage of repeated
      episodes of acute urticaria/angio-oedema reactions induced by sodium benzoate is
      very low (2%). In view of our results, we suggest that when faced with patients
      who have suffered adverse reactions that could be attributed to sodium benzoate,
      physicians should also carefully evaluate other possible causes.

PMID- 15491436
TI  - Characterization of the cellular infiltrate during successful topical treatment
      of lentigo maligna with imiquimod.
AB  - Lentigo maligna (LM) is an in situ melanoma which usually occurs in sun-damaged
      skin on the head and neck of elderly patients. Depending on the anatomical site
      and its size treatment of LM can be problematic and usually includes surgical
      excision or radiotherapy. Recent reports indicate that topical imiquimod may be
      an effective treatment. However, no data on the underlying immune response in the
      skin during treatment of LM with topical imiquimod are available so far. We
      report a 62-year-old caucasian woman with a histologically verified LM which was
      successfully treated with topical imiquimod 5% cream. Skin biopsy specimens were
      obtained before, during (at week 10) and 4 weeks after cessation of topical
      treatment with imiquimod 5% cream. Histological and immunohistochemical
      examination was performed in order to detect residual atypical melanocytes and to
      characterize the inflammatory infiltrate. A complete clinical and histological
      clearance of the skin lesion was achieved, with no recurrence up to 9 months
      after the end of treatment. During topical application of imiquimod 5% cream a
      depletion of epidermal and dermal CD1a+ dendritic cells was observed. The
      inflammatory infiltrate consisted of CD68+ macrophages and mainly of CD3+ T cells
      with a slight predominance of CD8+ T cells. An enhanced expression of granzyme B
      and TIA-1 was also noted particularly in the epidermis and near the
      dermoepidermal junction. In conclusion, our data indicate that imiquimod 5% cream
      induces a cytotoxic T-cell-mediated immune response in situ which may account for
      the complete destruction of the malignant melanocytes in LM. Further clinical
      trials and longer follow-up periods on the use of imiquimod for LM are warranted.

PMID- 15491437
TI  - Whipple's disease presenting with symmetrical panniculitis.
AB  - Specific cutaneous involvement in Whipple's disease is extremely rare. The
      condition usually runs a chronic course, with symptoms preceding diagnosis by
      years or even decades. We report a 44-year-old man who presented with a rapid
      onset of progressive, extensive, symmetrical plaques of panniculitis affecting
      the inner thighs and forearms. He had accompanying large joint arthritis and was
      profoundly anaemic. Biopsy of the subcutis revealed a florid septal panniculitis
      with infiltration of the septa by foamy macrophages containing intracellular
      granules that stained strongly with periodic acid-Schiff reagent. A similar but
      more intense infiltrate was seen in the small bowel lamina propria, and a
      diagnosis of Whipple's disease was made. Symmetrical panniculitis has not
      previously been reported as a manifestation of Whipple's disease.

PMID- 15491438
TI  - Successful use of acitretin in conjunction with narrowband ultraviolet B
      phototherapy in a child with severe pustular psoriasis, von Zumbusch type.
AB  - Severe pustular psoriasis von Zumbusch type is a therapeutic challenge not only
      in adults, but even more in children. We report a 3(1/2)-year-old boy who
      developed a generalized flare of diffusely scattered pustules on erythematous
      skin which rapidly progressed to large exuding areas. The clinical presentation
      and investigations including histopathological examination of a biopsy and
      negative bacterial cultures were consistent with the diagnosis of pustular
      psoriasis von Zumbusch type. Upon initial treatment with methylprednisolone,
      acitretin and antibiotics the extent of the disease declined. However, several
      attempts to reduce the dose of the oral corticosteroid were followed by immediate
      severe flares. Additional treatment with narrowband ultraviolet B (NB-UVB, 311
      313 nm UVB) resulted in a rapid arrest of disease activity and allowed the
      corticosteroid to be tapered off. After 10 irradiations the patient was both off
      steroid and disease free. NB-UVB therapy was subsequently reduced to twice-weekly
      exposures and acitretin gradually diminished to a maintenance dose of 0.3 mg kg(
      1) daily. We conclude that NB-UVB in conjunction with acitretin is a potent
      therapeutic regimen for the treatment of severe pustular psoriasis von Zumbusch
      type in childhood.

PMID- 15491439
TI  - Rosacea fulminans in pregnancy.
AB  - Rosacea fulminans is a rare condition with a female preponderance and unknown
      aetiology, characterized by the abrupt onset of papules, pustules and erythema
      affecting the face. Corticosteroids and isotretinoin are regarded as the two main
      therapeutic agents. We report a case associated with pregnancy, and discuss the
      therapeutic implications. This is the first published report of rosacea fulminans
      in pregnancy complicated by stillbirth.

PMID- 15491440
TI  - Hepatoerythropoietic porphyria: a missense mutation in the UROD gene is
      associated with mild disease and an unusual porphyrin excretion pattern.
AB  - Hepatoerythropoietic porphyria (HEP) is an uncommon inherited cutaneous
      porphyria, related to porphyria cutanea tarda, that results from severe
      uroporphyrinogen decarboxylase (UROD) deficiency. It is characterized clinically
      by the onset in early childhood of severe lesions on sun-exposed skin. We
      describe a man aged 38 years with an unusually mild form of the disease that
      started in his early teens. Our data confirm that homozygosity for the F46L
      mutation in the UROD gene causes a mild form of HEP and show that this genotype
      may be associated with a unique urinary porphyrin excretion pattern in which
      pentacarboxylic porphyrin predominates.

PMID- 15491441
TI  - Two cases of cutaneous umbilical endosalpingiosis.

PMID- 15491443
TI  - Successful treatment of recalcitrant Wegener's granulomatosis of the skin with
      tacrolimus (Prograf).

PMID- 15491442
TI  - Scabies infestation of a basal cell carcinoma.

PMID- 15491444
TI  - Human mast cells and extracellular matrix: immunohistochemical studies of normal
      skin and inflammatory dermatoses.

PMID- 15491445
TI  - A de novo heterozygous point mutation in the p63 gene causing the syndrome of
      ectrodactyly, ectodermal dysplasia and facial clefting.

PMID- 15491446
TI  - Basalioma after amiodarone therapy-not only in Britain.

PMID- 15491447
TI  - Azelaic acid as a new treatment for perioral dermatitis: results from an open
      study.

PMID- 15491449
TI  - Actin and calponin expression in basal cell carcinoma.

PMID- 15491450
TI  - Contact urticaria due to p-chloro-m-cresol.

PMID- 15491451
TI  - Leucocytoclastic vasculitis, hepatitis C virus-associated mixed cryoglobulinaemia
      with biclonal gammopathy and Waldenstrom macroglobulinaemia.

PMID- 15491453
TI  - Primary cutaneous anaplastic large cell lymphoma in an elderly patient with
      cryoglobulinaemic hepatitis C virus infection.

PMID- 15491452
TI  - A case of severe tongue ulceration and laryngeal inflammation induced by low-dose
      nicorandil therapy.

PMID- 15491454
TI  - Multilocular giant epidermal cyst.

PMID- 15491455
TI  - Contact urticaria to play dough: a possible sign of dietary allergy.

PMID- 15491456
TI  - Cutaneous metastatic malignant mixed mullerian tumour mimicking cutaneous
      leiomyosarcoma: a case report.

PMID- 15491457
TI  - Treatment of eosinophilic pustular folliculitis (Ofuji's disease) with tacrolimus
      ointment.

PMID- 15491459
TI  - Oral Candida isolates in patients undergoing radiotherapy for head and neck
      cancer: prevalence, azole susceptibility profiles and response to antifungal
      treatment.
AB  - Oral pseudomembranous candidiasis and mucositis were assessed in 39 patients
      receiving a total dose of 39-70 Gy radiotherapy for head and neck cancer.
      Mucositis was scored using the Radiation Therapy Oncology Group criteria, and
      oral candidiasis was diagnosed on the basis of clinical evaluation and
      quantitative laboratory findings. Radiation-induced mucositis was observed in
      9/39 patients. Only 3/39 patients discontinued radiotherapy due to acute severe
      mucosal effects. Candidiasis (colony-forming units 35 to > or = 60/lesion)
      associated with mucositis was diagnosed in 30/39 patients: the most frequent
      aetiology of the infection was Candida albicans (n = 23), followed by Candida
      glabrata (n = 3), Candida krusei (n = 2), Candida tropicalis (n = 1) and Candida
      kefyr (n = 1). Patients with confirmed oral pseudomembranous candidiasis were
      treated with either fluconazole 200 mg/day or itraconazole 200 mg/day for 2
      weeks. Clinical improvement and concomitant negative Candida cultures (mycologic
      cure) were the criteria determining a response to antifungal treatment. Etest
      revealed very low voriconazole MICs (0.004-0.125 microg/ml) for all isolates, and
      fluconazole resistance for eight C. albicans strains (MIC > 64 microg/ml) and for
      the C. krusei isolates (MIC > 32 microg/ml). The same strains showed itraconazole
      susceptibility dose dependence (MIC 0.5 microg/ml). Despite the itraconazole
      susceptible dose dependent MIC readings, all patients with oral pseudomembranous
      candidiasis caused by these strains responded to antifungal treatment with 200
      mg/day itraconazole. Oral mycologic surveillance of patients undergoing
      radiotherapy for head and neck malignancies and susceptibility testing of
      isolates may be indicated in cases with mucositis-associated confirmed oral
      pseudomembranous candidiasis to ensure prompt administration of targeted
      antifungal treatment. On the basis of the low MIC values found, clinical
      evaluation of voriconazole is indicated for management of oral pseudomembranous
      candidiasis refractory to other azoles.

PMID- 15491460
TI  - Use of checkerboard DNA-DNA hybridization to study complex microbial ecosystems.
AB  - It has been difficult to conduct large scale studies of microbiologically complex
      ecosystems using conventional microbiological techniques. Molecular
      identification techniques in new probe-target formats, such as checkerboard DNA
      DNA hybridization, permit enumeration of large numbers of species in very large
      numbers of samples. Digoxigenin-labeled whole genomic probes to 40 common
      subgingival species were tested in a checkerboard hydridization format.
      Chemifluorescent signals resulting from the hybridization reactions were
      quantified using a Fluorimager and used to evaluate sensitivity and specificity
      of the probes. Sensitivity of the DNA probes was adjusted to detect 10(4) cells.
      In all, 93.5% of potential cross-reactions to 80 cultivable species exhibited
      signals <5% of that detected for the homologous probe signal. Competitive
      hybridization and probes prepared by subtraction hybridization and polymerase
      chain reaction were effective in minimizing cross-reactions for closely related
      taxa. To demonstrate utility, the technique was used to evaluate 8887 subgingival
      plaque samples from 79 periodontally healthy and 272 chronic periodontitis
      subjects and 8126 samples from 166 subjects taken prior to and after periodontal
      therapy. Significant differences were detected for many taxa for mean counts,
      proportion of total sample, and percentage of sites colonized between samples
      from periodontally healthy and periodontitis subjects. Further, significant
      reductions were observed post therapy for many subgingival species including
      periodontal pathogens. DNA probes used in the checkerboard DNA-DNA format provide
      a useful tool for the enumeration of bacterial species in microbiologically
      complex systems.

PMID- 15491461
TI  - Investigation of bacterial communities associated with asymptomatic and
      symptomatic endodontic infections by denaturing gradient gel electrophoresis
      fingerprinting approach.
AB  - The purpose of the present study was to investigate the bacterial communities
      associated with asymptomatic and symptomatic endodontic infections and to compare
      denaturing gradient gel electrophoresis (DGGE) fingerprinting patterns of these
      two clinical conditions. The root canal microbiota of teeth associated with
      asymptomatic or symptomatic periradicular lesions was profiled by the PCR-DGGE
      method and then compared, taking into consideration the banding patterns.
      Bacteria were present in all examined cases. Comparative analysis of the two
      clinical conditions revealed bands that were common to both symptomatic and
      asymptomatic cases, but most DGGE bands appeared to be unique for each clinical
      condition. No single band occurred in all profiles. The mean number of bands
      detected in the 16S rDNA community profiles were 12.1 +/- 9.4 (range 2-29) for
      symptomatic samples and 6.7 +/- 2.7 (range 2-11) for asymptomatic ones.
      Clustering methods and principal component analysis of DGGE banding pattern
      placed the samples according to the presence or absence of symptoms. Four intense
      bands that were excised from the gel and sequenced showed similarities to species
      of the Campylobacter genus (found in 5/12 asymptomatic and in 3/11 symptomatic
      cases), Fusobacterium genus (4/11 symptomatic cases), Acinetobacter genus (5/12
      asymptomatic cases), and Enterobacteriaceae family (11/12 asymptomatic and 2/11
      symptomatic cases). The profiles of the predominant bacterial community appeared
      to be unique for each individual. These findings confirm that endodontic
      infections are polymicrobial and showed that there are significant differences in
      the predominant bacterial composition between asymptomatic and symptomatic cases.

PMID- 15491462
TI  - Genotypic diversity of oral Actinomyces naeslundii genospecies 1 and 2 in caries
      active preschool children.
AB  - A total of 991 isolates of Actinomyces naeslundii were obtained from sound
      approximal tooth sites in either caries-active (n = 35) or caries-free (n = 20)
      preschool children. From this group of isolates, 101 strains were chosen to study
      the genotypic diversity of A. naeslundii genospecies 1 (n = 30), catalase
      positive (n = 30), and catalase-negative genospecies 2 (n = 41). Polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP), with a pair of
      primers targeting the 16S ribosome RNA gene (16S rDNA), and MnlI digestion
      together with randomly amplified polymorphic DNA (RAPD) with eight arbitrary,
      single 10-mer primers were performed to generate genetic profiles of selected
      Actinomyces isolates. The hierarchic relationships of genetic profiles were
      finally analyzed using computerized dendrograms. There was no significant
      difference in the prevalence rates and proportions of either genospecies 1 or 2
      between the caries-free and caries-active groups, although a higher prevalence of
      genospecies 2 was noted in the total population. Dendrogram analyses of the 16S
      rDNA PCR-RFLP profiles revealed that all strains belonging to A. naeslundii
      genospecies 1 could be subgrouped into three genotypes (T7, T18, and T19), with a
      single predominant genotype, T18 (27/30). Catalase-positive strains for
      genospecies 2 fell into three subtypes (T4, T7, and T17), whereas the catalase
      negative counterparts were distributed amongst 16 subtypes. No specific genotype
      was significantly associated with caries activity. We conclude that heterogeneous
      subgroups of A. naeslundii genospecies 1 and 2, particularly the latter, are the
      constituent flora of dental plaque in children and may contribute to the
      pathogenesis of childhood caries.

PMID- 15491463
TI  - Detection frequency of periodontitis-associated bacteria by polymerase chain
      reaction in subgingival and supragingival plaque of periodontitis and healthy
      subjects.
AB  - The aim of this study was to compare the detection frequencies of 25 bacterial
      species in subgingival and supragingival plaque of 18 untreated periodontitis
      subjects and 12 periodontally healthy subjects. Genomic DNA was extracted from
      subgingival and supragingival plaque samples, and bacterial detection was
      performed by polymerase chain reaction of the 16S rRNA genes. Fourteen bacteria
      showed no relationship with periodontitis, and 11 of these 14 species were
      frequently detected (> or =50%) in subgingival plaque in both periodontitis and
      healthy subjects. Nine bacteria such as Eubacterium saphenum, Prevotella
      intermedia, and Treponema denticola seemed to be related to periodontitis; their
      detection frequencies in subgingival plaque samples were higher in periodontitis
      than in healthy subjects, but these differences were not statistically
      significant by multiple comparisons (0.002< or =P<0.05). Two species
      (Mogibacterium timidum and Porphyromonas gingivalis) were detected significantly
      more frequently in subgingival plaque of periodontitis subjects than of healthy
      subjects (P<0.002), with P. gingivalis being detected only in periodontitis
      subjects, suggesting that these two species are closely related to periodontitis.
      There were no significant differences in the detection frequencies of the 25
      bacteria between subgingival and supragingival plaque, suggesting that the
      bacterial flora of supragingival plaque reflects that of subgingival plaque.

PMID- 15491464
TI  - Molecular analysis of age-related changes of Streptococcus anginosus group and
      Streptococcus mitis in saliva.
AB  - The purpose of this study was to survey the prevalence of streptococcal species,
      especially Streptococcus anginosus (which has been reported to be associated with
      cancer in the upper digestive tract), Streptococcus constellatus, and
      Streptococcus intermedius in the saliva of different age groups. A sequence
      analysis of 16S rDNA was performed and DNA quantified using real-time polymerase
      chain reaction. The S. anginosus level increased with age, whereas the levels of
      S. constellatus and S. intermedius did not change. Streptococcus mitis was the
      predominant species in the saliva of all the age groups but, unlike the S.
      anginosus, the proportion of S. mitis in the salivary bacteria decreased with
      age. The increase in S. anginosus with age should be carefully monitored because
      of its association with diseases, including cancer.

PMID- 15491465
TI  - Alkali-resistant bacteria in root canal systems.
AB  - The aim of this study was to isolate and identify alkali-resistant bacteria from
      the dentin of infected root canals. Bacteria from homogenized dentin powder made
      up from infected root canal walls from human teeth were cultured on buffer
      enriched Brain Heart Infusion agar supplemented with 4% sheep blood (BHI-blood
      agar), adjusted to pH 7.0, 9.0 or 10.0. Incubation took place for 7 days at 37
      degrees C in an anaerobic glove box. Bacterial strains selected according to
      colony and morphology were subcultured in buffer-enriched BHI broth adjusted to
      pH 9.0, 10.0 or 11.0 to confirm their growth as alkali-resistant bacteria.
      Polymerase chain reaction amplification using specific primer sets and 16S rDNA
      sequence analysis was performed for identification of alkali-resistant isolates.
      In the present study, 37 teeth extracted from 37 patients were used for
      preparation of the dentin powder samples. Bacteria were detected in 25 samples
      when standard BHI-blood agars (pH 7.0) were used. Of these, 29 strains from 15
      samples were alkali resistant, 25 strains growing at pH 9.0 and 4 at pH 10.0. The
      alkali-resistant strains included Enterococcus faecium (10 strains) and
      Enterococcus faecalis (2 strains), Enterobacter cancerogenus (1 strains),
      Fusobacterium nucleatum (1 strains), Klebsiella ornithinolytica (2 strains),
      Lactobacillus rhamnosus (2 strains), Streptococcus anginosus (2 strains),
      Streptococcus constellatus (3 strains), and Streptococcus mitis (2 strains).
      Three strains were also identified as bacteria of genus Firmicutes or
      Staphylococcus at the genus level. The present study showed that many bacterial
      species in infected root canal dentin were alkali-resistant at pH 9.0 and/or pH
      10.0, and belonged mainly to the genus Enterococcus.

PMID- 15491466
TI  - Role of a Streptococcus gordonii copper-transport operon, copYAZ, in biofilm
      detachment.
AB  - Streptococcus gordonii is a pioneer oral bacterium that is associated with the
      initiation of dental plaque development. Located downstream of the S. gordonii
      adc operon, which is involved in competence and biofilm formation, were three
      open reading frames, designated copY, copA and copZ. These open reading frames
      were homologous to the copYAZ genes in Streptococcus mutans that are involved in
      copper homeostasis and biofilm detachment. This study examined whether copYAZ
      genes play any role in the biofilm formation and detachment of S. gordonii. The
      copY gene encodes a 143-amino acid protein homologous to the negative
      transcriptional regulator of a copper-transport operon, copA encodes a 748-amino
      acid copper-transporting P-type ATPase, and copZ encodes a 69-amino acid putative
      metallochaperone protein in S. mutans. Each open reading frame in the copYAZ
      operon in S. gordonii was inactivated by insertional mutation and the growth,
      biofilm formation and detachment of each mutant were examined. S. gordonii
      copY::specR, copA::specR, and copZ::specR mutants were able to form biofilms on
      both polystyrene and glass surfaces. However, inactivation of copZ and to a
      lesser extent copY resulted in phenotypes that were defective in biofilm
      detachment, which is consistent with previous observations in S. mutans and
      suggests that the trace element copper might influence biofilm detachment of
      bacterial biofilms.

PMID- 15491467
TI  - Resistance to human beta-defensins is common among oral treponemes.
AB  - BACKGROUND/AIMS: Oral treponemes are implicated in the pathogenesis of
      periodontal disease. We have previously shown that Treponema denticola ATCC type
      strains and strain GM-1 are resistant to killing by human beta-defensins (hbetaD)
      1 and -2. We hypothesize that resistance to beta-defensins is a common feature of
      oral treponemes, which allows colonization and persistence in the oral cavity. In
      this study, we tested additional isolates of T. denticola, as well as six other
      species of treponemes, for resistance to hbetaD-1, -2 and -3. We also examined
      the four ATCC strains of T. denticola and strain GM-1 for resistance to hbetaD-3.
      METHODS: Resistance was determined by motility and Alamar Blue assays for
      metabolic activity. RESULTS: All T. denticola strains tested were resistant to
      hbetaD-1, -2 and -3, with the exception of strain Ambigua, which was sensitive to
      hbetaD-2 and -3. All other treponemes except Treponema vincentii were resistant
      to hbetaD-1. Treponema pectinovorum was sensitive to hbetaD-2, while T.
      vincentii, T. pectinovorum and Treponema maltophilum were sensitive to hbetaD-3.
      Escherichia coli was used as a control organism and was killed by all three
      defensins. CONCLUSION: Resistance to the constitutively expressed hbetaD-1 may
      assist treponemes in initial colonization of epithelial surfaces, while
      resistance to the inducible hbetaD-2 and -3 would allow some treponemes to
      survive in active periodontal lesions.

PMID- 15491468
TI  - Transmission of Streptococcus mutans in a group of Turkish families.
AB  - BACKGROUND/AIMS: To investigate the transmission of Streptococcus mutans in a
      group of Turkish families using AP-polymerase chain reaction (PCR) detection.
      METHODS: Eight mothers who had high S. mutans levels in unstimulated saliva and 8
      children aged between 2 and 3 years participated in the study. Plaque samples
      from each child were collected with the tips of sterile toothpicks for S. mutans
      counts. Although not part of the original study design, S. mutans samples were
      also obtained from the unstimulated saliva of the three fathers who shared the
      same households. Three typical isolates of S. mutans were isolated from TYCSB
      agar of each subject and identified by sugar fermentation tests. S. mutans ATCC
      10449 was used as the reference strain. AP-PCR was conducted with OPA-05 primer.
      RESULTS: All of the mothers and fathers shared the similar genotypes within their
      children. The fathers also harbored similar genotypes to their spouses.
      CONCLUSION: The mothers or the fathers could be the source for the transmission
      of S. mutans to their children.

PMID- 15491469
TI  - Serum levels of soluble urokinase plasminogen activator receptor is associated
      with parasitemia in children with acute Plasmodium falciparum malaria infection.
AB  - Serum levels of soluble urokinase plasminogen activator receptor (suPAR) are
      significantly elevated and of prognostic value in patients suffering from serious
      infectious diseases such as HIV and tuberculosis. Our objective was to
      investigate suPAR levels during symptomatic malaria infection and 7 days after
      treatment. Children younger than 6 years who presented with fever or other
      symptoms compatible with malaria were enrolled. Blood films and samples were
      collected on day 0 and day 7. Twenty-five children were allocated to each of
      three groups according to the amount of Plasmodium falciparum detected in their
      initial blood film. Children in group 1 had parasite densities in excess of 20
      parasites per 200 leucocytes. The median plasma suPAR level was 6.49 ng/mL
      (interquartile range [IQR]: 4.90-7.61) and correlated to parasitemia (Spearman
      0.43, P < 0.0001). Blood was obtained from 20 children in group 1 after 7 days of
      treatment. All became malaria negative in their blood slides and all decreased in
      suPAR level to median 3.48 ng/mL (IQR: 3.08-3.91) (P < 0.0001). Group 2 consisted
      of 25 children with 1-20 parasites in their blood slide. The suPAR level was
      median 2.91 ng/mL (IQR: 2.27-4.40) and decreased with median 0.5 ng/mL following
      treatment (P = 0.0002). Group 3 showed to be negative in their blood slides and
      most received antibiotic treatment. suPAR decreased from median 3.26 ng/mL (IQR:
      2.77-4.46) to median 2.47 ng/mL (IQR: 2.01-3.75), on day 7 (P = 0.006). This
      study demonstrates an important association between suPAR and acute malaria
      infection in humans.

PMID- 15491470
TI  - Activation by malaria antigens renders mononuclear cells susceptible to HIV
      infection and re-activates replication of endogenous HIV in cells from HIV
      infected adults.
AB  - We have tested the hypothesis that activation of T cells by exposure to malaria
      antigens facilitates both de novo HIV infection and viral reactivation and
      replication. PBMC from malaria-naive HIV-uninfected European donors could be
      productively infected with HIV following in vitro stimulation with a lysate of
      Plasmodium falciparum schizonts and PBMC from malaria-naive and malaria-exposed
      (semi-immune) HIV-positive adults were induced to produce higher levels of virus
      after stimulation with the same malaria extract. These findings suggest that
      effective malaria control measures might con-tribute to reducing the spread of
      HIV and extending the life span of HIV-infected individuals living in malaria
      endemic areas.

PMID- 15491471
TI  - A protective merozoite protein of Plasmodium falciparum shares an epitope with
      surface antigens of Paramecium.
AB  - A Plasmodium falciparum cDNA expression clone, lambdaPf9, had been identified
      earlier as a protective epitope, using anti-lambdaPf9 antibodies and
      combinatorial phagotopes. A segment of the Pf9 gene showed homology with
      Paramecium immobilization surface antigens such as 51B, 51A and 156G. A synthetic
      Pf9-peptide was designed from this region, and specific antibodies were raised.
      Each of these anti-Pf9 antibodies and combinatorial reagents, as well as anti
      Paramecium 51B antibodies, recognized the Pf9-peptide on ELISA, and the same
      protein band in parasite immunoblots. The P. falciparum protein was released from
      the merozoite membrane fraction on treatment with PI-PLC, indicating the presence
      of a GPI anchor. Anti-Pf9-peptide antibodies specifically inhibited the growth of
      P. falciparum in culture. Immunofluorescence assays showed the reactivity of anti
      Pf9-peptide sera with P. falciparum merozoites and gametocytes, as well as on the
      surface of Paramecium tetraurelia. The Pf9-peptide was able to induce
      proliferation of splenic lymphocytes obtained from mice infected with the rodent
      malarial parasites Plasmodium berghei and Plasmodium yoelii. These results point
      towards Plasmodium Pf9 as a conserved novel protective protein, sharing an
      epitope with Paramecium surface antigens.

PMID- 15491472
TI  - IL-10 is not required to prevent immune hyperactivity during memory responses to
      Toxoplasma gondii.
AB  - Primary infection of IL-10 knockout (KO) mice with the protozoan parasite
      Toxoplasma gondii leads to a CD4(+)-T-cell dependent shock-like reaction with
      high systemic levels of IL-12 and IFN-gamma, severe liver pathology and death of
      mice. In the present study, this immune-mediated pathology was prevented by
      treatment of IL-10 KO mice with the anti-parasitic drug sulfadiazine, allowing
      these mice to progress to the chronic phase of infection. To address the role of
      endogenous IL-10 in the regulation of secondary immune responses to T. gondii, IL
      10 KO mice were infected with the avirulent Me49 strain of this parasite, treated
      with sulfadiazine for 2 weeks starting at day 3 p.i., and were rechallenged 6
      weeks p.i. with RH, a highly virulent strain of T. gondii. In these studies,
      chronically infected IL-10 KO mice survived secondary infection with RH and
      controlled parasite load. Although serum levels of IL-12 and IFN-gamma were
      higher in IL-10 KO mice than in wild type (WT) mice 8 days after RH rechallenge,
      these levels were well controlled in the absence of endogenous IL-10, suggesting
      that IL-10 is not required to down-regulate cytokine production during the memory
      response. Antigen-specific ex vivo recall responses further revealed that
      splenocytes from chronically infected WT and IL-10 KO mice responded to parasite
      antigen with similar production of IL-12 and IFN-gamma, and there was also no
      significant difference in ex vivo production of these cytokines by splenocytes in
      response to parasite antigen 7 days after secondary infection with T. gondii.
      Furthermore, IL-10 KO mice immunized with the Ts-4 vaccine-strain of T. gondii
      were protected when rechallenged with the virulent RH strain. Together, these
      studies demonstrate that the inhibitory effect of IL-10, which is required to
      prevent immune-mediated pathology during primary infection, is not required to
      prevent immune hyperactivity during a secondary response to T. gondii, and a
      highly effective memory response is generated in the absence of endogenous IL-10.

PMID- 15491473
TI  - Entamoeba histolytica cysteine protease 2 (EhCP2) modulates leucocyte migration
      by proteolytic cleavage of chemokines.
AB  - Human amoebiasis is a disease produced by infection with the protozoan Entamoeba
      histolytica currently affecting many millions of people worldwide. Amoebic
      colitis is the most common clinical manifestation. Host protective immunity
      involves participation of both humoral and cellular responses. However, the
      mechanisms involved in immune evasion are not clear and remain under
      investigation. One of these mechanisms could be associated with the ability of
      parasite proteases to modulate or interfere with the inflammation process, which
      is initiated by expression of pro-inflammatory cytokines such as chemokines. To
      further clarify the potential role of cysteine proteases in modulating chemokine
      mediated functions, we have analysed the ability of Entamoeba histolytica
      cysteine protease 2 (EhCP2) to have an effect on the chemotaxis of leucocytes by
      chemokine cleavage. We find that EhCP2 is capable of cleaving chemokines CCL2,
      CCL13 and CXCL8, and the resulting proteolysis products modulate the chemotaxis
      of leucocytes when compared to that induced by intact chemokine. Thus, the
      extracellular activity of the cysteine proteases affects chemokine-mediated
      responses and could be considered as part of the mechanisms used by Entamoeba
      histolytica to circumvent the host immune responses.

PMID- 15491474
TI  - Establishment of Neospora caninum antigen-specific T cell lines of primarily CD4
      T cells.
AB  - Neosporosis is an important cause of pregnancy loss in cattle worldwide.
      Protective immunity against Neospora caninum infection may include both cell
      mediated (CMI) and humoral immune responses. This study was to establish short
      term antigen-specific T cell lines composed of primarily CD4(+)T cells from
      peripheral blood lymphocytes (PBL) of infected cows, which may be used to
      identify immunodominant antigens for the development of N. caninum vaccines.
      Crude N. caninum tachyzoite antigen was prepared from in vitro derived N. caninum
      tachyzoites. Multiple T cell lines were established and maintained for 11 weeks
      by weekly re-stimulation with N. caninum antigen and antigen-presenting cells.
      All cell lines responded highly to antigen between weeks 3 and 11.
      Phenotypically, these cells were composed primarily of CD4(+)T cells between
      weeks 2-8, with a gradual expansion of gamma/delta(+)T cells thereafter. The
      results indicate that N. caninum-specific T cell lines can be established and
      maintained without exogenous T cell growth factors and may be used to identify N.
      caninum antigens. This research will enhance our understanding of bovine CMI to
      neosporosis and may facilitate development of a proven neosporosis vaccine.

PMID- 15491475
TI  - School vision screening, ages 5-16 years: the evidence-base for content,
      provision and efficacy.
AB  - The optometric profession in the UK has a major role in the detection, assessment
      and management of ocular anomalies in children between 5 and 16 years of age. The
      role complements a variety of associated screening services provided across
      several health care sectors. The review examines the evidence-base for the
      content, provision and efficacy of these screening services in terms of the
      prevalence of anomalies such as refractive error, amblyopia, binocular vision and
      colour vision and considers the consequences of their curtailment. Vision
      screening must focus on pre-school children if the aim of the screening is to
      detect and treat conditions that may lead to amblyopia, whereas if the aim is to
      detect and correct significant refractive errors (not likely to lead to
      amblyopia) then it would be expedient for the optometric profession to act as the
      major provider of refractive (and colour vision) screening at 5-6 years of age.
      Myopia is the refractive error most likely to develop during primary school
      presenting typically between 8 and 12 years of age, thus screening at entry to
      secondary school is warranted. Given the inevitable restriction on resources for
      health care, establishing screening at 5 and 11 years of age, with exclusion of
      any subsequent screening, is the preferred option.

PMID- 15491476
TI  - Frequency doubling perimetry screening mode compared to the full-threshold mode.
AB  - The diagnostic performance of the frequency doubling perimetry (FDT) C20-1
      screening mode was compared to that of the C20 full-threshold mode. For the
      number of defects p < 1% in the total deviation plot, both modes appeared to
      perform similarly in terms of sensitivity, specificity, and area under the
      receiver-operating characteristic (ROC) curve. Different cut-off points should be
      applied for both modes to obtain equal sensitivity and specificity values, and -
      related to that - for most subjects more defects were found in full-threshold
      mode than in screening mode. For the screening mode, we found a sensitivity of
      0.91 and a specificity of 0.88 at a cut-off point of >0 defects, and an area
      under the ROC curve of 0.93.

PMID- 15491477
TI  - An evaluation of algorithms designed to classify the results from frequency
      doubling perimetry.
AB  - All previously published algorithms for the interpretation of frequency doubling
      perimetry test results were compared in full-threshold mode in a large group of
      glaucoma patients (n = 452) and normal subjects (n = 237). Areas under the
      receiver-operating characteristic (ROC) curve ranged from 0.86 to 0.92. None of
      the algorithms performed substantially better than simply counting the number of
      defects p < 1% in the total deviation plot. For this algorithm, we found a
      sensitivity of 0.90 and a specificity of 0.81 at a cut-off point of >1 defect,
      and an area under the ROC curve of 0.92.

PMID- 15491478
TI  - Non-compliance with lens care and maintenance in diabetic contact lens wearers.
AB  - We hypothesize that diabetic contact lens wearers may represent a special group
      displaying higher levels of compliance with their lens care regimens as a result
      of learned behaviour relating to maintenance of their diabetic condition. To test
      this hypothesis, a prospective, single centre, controlled, masked study was
      performed whereby 29 diabetic contact lens patients and 29 non-diabetic control
      subjects were issued with disposable hydrogel contact lenses and a multipurpose
      lens care regimen. All participants were given identical instruction on lens care
      and maintenance. Compliance levels were assessed at a 12-month aftercare
      appointment by demonstration and questionnaire. Twenty-four different aspects of
      compliance were scored, 12 by observation and 12 by questionnaire report, of
      which only two showed a significant difference between the diabetic and control
      groups. Although the combined population of contact lens wearers was generally
      compliant, there were examples of non-compliance in both groups. Neither the
      duration of diabetes nor the degree of metabolic control appeared to have a
      significant effect on compliance. The results suggest that eye care practitioners
      cannot assume that diabetic patients will be more compliant with contact lens
      care and maintenance than non-diabetic patients.

PMID- 15491479
TI  - Matrix-based calculation scheme for toric intraocular lenses.
AB  - BACKGROUND AND PURPOSE: While a number of intraocular lens power prediction
      formulas are well established for determination of spherical lenses, no common
      strategy is published for the computation of toric intraocular lenses. The
      purpose of this study is to describe a paraxial computing scheme using 4 x 4
      system matrices to describe the 'optical system eye' containing astigmatic
      refractive surfaces with their axes at random. METHODS: Based on the definition
      of a centred optical system in the paraxial Gaussian space containing astigmatic
      surfaces using 4 x 4 refraction and translation matrices, we derived a
      methodology for calculating the refractive power of thin and thick toric
      intraocular lenses by solving a linear equation system. In a second step, we
      derived a methodology for prediction of the residual spectacle refraction after
      implantation of any toric lens implant with any orientation. RESULTS: The
      capabilities of this computing scheme are demonstrated with three examples. In
      example 1 we calculate a 'thin toric lens' for compensation of a corneal
      astigmatism to achieve a spherical target refraction. In example 2 we compute a
      'thick toric lens', which has to compensate for an oblique corneal astigmatism
      and rotate the spectacle cylinder to the 'against the rule' position to enhance
      near vision. In example 3 we predict the residual refraction at the corneal plane
      after implantation of a thick toric lens, when the cylinder of the lens implant
      is compensating the corneal cylinder in part and the axis of implantation is not
      fully aligned with the axis of the corneal astigmatism. CONCLUSION: We present an
      en bloc matrix-based strategy for the calculation of thick or thin toric
      intraocular lenses, with the flexibility of crossing an unlimited number of
      cylinders with restrictions to paraxial optics. The resulting system matrix S is
      written as a product of 4 x 4 refraction and translation matrices. Residual
      refraction at the corneal (contact lens) or spectacle plane can be derived by
      inverting the order of matrices for calculation of the system matrix.

PMID- 15491480
TI  - Measurement of refractive error and accommodation with the photorefractor
      PowerRef II.
AB  - The infrared photorefractor PowerRef II (PR II; PlusoptiX AG, Nurnberg, Germany)
      uses the principle of eccentric photorefraction. In eight subjects the mean non
      cycloplegic refraction measured with the 'Full Scan' mode of the PR II at a far
      viewing distance (0.2 D) was significantly more hypermetropic by 0.6 D compared
      with subjective refraction. The mean accommodation differed by about this same
      amount between the PR II and the Canon R1 at three different viewing distances
      (3, 2 and 1 D). The PR II refraction at the 1 m reference distance was 0.25 D
      more hypermetropic compared with the subjective refraction at far (5 m); these
      measures were moderately correlated (r = 0.7). To determine temporal changes, the
      'Dynamic Scan' mode was used over a 2-min period: the mean intraindividual
      standard deviation was 0.32 mm for pupil diameter and 0.29 D for accommodation,
      while the absolute measurement error of the 'Dynamic Scan' was found to be <0.12
      D for the accommodation data. Interindividual reliabilities were satisfactory.
      However, the PR II did not provide a continuous stream of data and the specified
      sampling frequency of 25 Hz was rarely realized.

PMID- 15491481
TI  - Statistical normal values of visual parameters that characterize binocular
      function in children.
AB  - A wide range of visual parameters used to evaluate binocular function were
      evaluated in a paediatric population (1056 subjects aged 6-12 years). Mean values
      are provided for these ages in optometric tests that directly assess the vergence
      system, horizontal phorias for near and far vision (measured by a modified
      version of the Thorington method), negative and positive vergence amplitude for
      near and far vision (step vergence testing), vergence facility (flippers 8 Delta
      BI/8 Delta BO), and near-point of convergence (penlight push-up technique and red
      lens push-up technique), as well as stimulus accommodative
      convergence/accommodation ratio and stereoacuity (Randot test) which provide an
      overall evaluation of the vergence, accommodative and oculomotor systems. A
      statistical comparison (anova and Bonferroni post hoc test) of these values
      between ages was performed. The differences, although statistically significant,
      were not clinically meaningful, and therefore we identified two trends in the
      behaviour of these parameters. For all parameters, except for vergence facility,
      we established a single mean reference value for the age range studied. The
      difference between the means for vergence facility indicated the need to divide
      the population into two age ranges (6-8 and 8-12 years). This study establishes
      statistical normal values for these parameters in a paediatric population and
      their means are a valuable instrument for separating children with binocular
      anomalies from those with normal binocular vision.

PMID- 15491482
TI  - A comparison of cup-to-disc ratio measurement in normal subjects using optical
      coherence tomography image analysis of the optic nerve head and stereo fundus
      biomicroscopy.
AB  - PURPOSE: To determine the relationships between morphometric optic nerve head
      (ONH) characteristics defined using optical coherence tomography (OCT) and
      clinical judgments of cup-to-disc (CD) ratios. METHODS: CD ratios were estimated
      in 20 subjects by two experienced clinicians using stereo fundus biomicroscopy.
      Sagittal OCT images were obtained in positions defined by clinicians
      corresponding to the location of their horizontal and vertical CD ratio
      estimates. To estimate CD ratios using the OCT images, disc width was defined as
      the separation of the terminations of the retinal pigment epithelium on each side
      of the image. OCT cup widths were determined using two criteria: the first
      measured the separation of cup walls halfway down each side and the second
      estimated the separation 1/3 down each side. Cups that were less than 150 microm
      deep were defined as flat for the OCT images. Data were analysed using mean and
      standard deviation of the differences between clinical estimates and imaging
      techniques as well as using intraclass correlations (ICC). RESULTS: Between
      techniques, the range of ICCs for the 1/2 depth criterion was 0.74-0.90 and for
      the 1/3 criterion was 0.59-0.81. The limits of agreement for the 1/2 criterion
      were also better than the 1/3 criterion. CONCLUSION: Accurate measures of CD
      ratio may be derived from OCT ONH images. Estimates of clinical CD ratios in
      normal subjects appear to be made using depth judgments closer to 1/2 of the way
      down the cup than 1/3.

PMID- 15491483
TI  - Impact of manufacturing technology and material composition on the mechanical
      properties of hydrogel contact lenses.
AB  - Hydrogel materials are not only different as a result of different co-monomer
      compositions but also as a result of the manufacturing method used to produce
      them. Hydrogel contact lenses fabricated by different methods are subjected to
      markedly different processing steps, which are likely to affect the resultant
      material network structure of a lens. The mechanical performance of five soft
      contact lens types was investigated using one conventional technique (tensile
      test) and three novel techniques (probe, tear and ball milling tests). The five
      lens groups consisted of three polyhydroxyethyl methacrylate (pHEMA) lenses which
      were each manufactured by a different technique: lathing, spin-casting and cast
      moulding, a HEMA/methacrylic acid (HEMA/MAA) cast-moulded lens and a
      HEMA/glycerol methacrylate (HEMA/GMA) cast-moulded lens. Overall, the results
      show that the best mechanical performance is obtained for the pHEMA lenses, with
      some differences occurring between the lenses. The HEMA/GMA lens showed the worst
      performance.

PMID- 15491484
TI  - Microfluctuations of wavefront aberrations of the eye.
AB  - To investigate fluctuations in the wavefront aberrations of the eye and their
      relation to pulse and respiration frequencies we used a wavefront sensor to
      measure the dynamics of the Zernike aberrations up to the polynomial fourth
      radial order. Simultaneously, the subject's pulse rate was measured, from which
      the instantaneous heart rate was derived. We used an auto-regressive process to
      derive the power spectra of the Zernike aberration signals, as well as pulse and
      instantaneous heart rate signals. Linear regression analysis was performed
      between the frequency components of Zernike aberrations and the pulse and
      instantaneous heart rate frequencies. Cross-spectrum density and coherence
      analyses were also applied to investigate the relation between fluctuations of
      wavefront aberrations, and pulse and instantaneous heart rate. The correlations
      between fluctuations of individual Zernike aberrations were also determined. A
      frequency component of all Zernike aberrations up to the fourth radial order was
      found to be significantly correlated with the pulse frequency (all R(2) >/= 0.51,
      p < 0.02), and a frequency component of nine out of 12 Zernike aberrations was
      also significantly correlated with instantaneous heart rate frequency (all R(2)
      >/= 0.46, p < 0.05). The major correlations among Zernike aberrations occurred
      between second-order and fourth-order aberrations with the same angular
      frequencies. Higher order aberrations appear to be related to the cardiopulmonary
      system in a similar way to that reported for the accommodation signal and pupil
      fluctuations.

PMID- 15491485
TI  - Relation between injected volume and optical parameters in refilled isolated
      porcine lenses.
AB  - PURPOSE: This study was performed to elucidate the correlation between added lens
      refill material and enhanced lens power as well as the correlation between lens
      refilling volume and accommodative amplitude as determined by equatorial
      stretching of ex vivo refilled pigs' lenses. METHODS: Nine porcine lenses were
      refilled with increasing amounts of silicone oil. After each refill step, the
      lens power, the lens power change, and the lens thickness were measured both in
      the relaxed state and with a 3-mm larger ciliary body diameter. In addition, the
      spherical aberration of the refilled lenses was also quantified. RESULTS:
      Injection of 0.04 mL silicone material into the relaxed lens enhanced the lens
      power by 1 D. A 0.54-mm increase of the lens thickness in relaxed lenses added 1
      D to the lens power. Increasing the lens refilling volume decreased the lens
      power changes measured at 3-mm ciliary body stretch. Spherical aberration was
      positive in the refilled lenses and increased with increasing lens refilling
      volume. CONCLUSION: The correlation found between the refilling volume and the
      lens power (0.04 mL D(-1)), as well as the correlation between the lens thickness
      and the lens power (0.54 mm D(-1)), might be important factors to be controlled
      in conjunction with surgery, as these also determine the lens power in the
      presence of this refill material. An increasing lens filling volume is associated
      with decreasing accommodative amplitude. The positive spherical aberration of
      refilled porcine lenses presents a sharp contrast to the negative aberration of
      natural pigs' lenses. Different lens contours and the transition from a gradient
      to a homogeneous refractive index might be responsible for this change in
      spherical aberration.

PMID- 15491486
TI  - The average eye.
AB  - For statistical and other purposes one needs to be able to determine an average
      eye. An average of refractive errors is readily calculated as an average of
      dioptric power matrices. A refractive error, however, is not so much a property
      of the eye as a property of the compensating lens in front of the eye. As such,
      it ignores other aspects of the optical character of the eye. This paper
      discusses the difficulties of finding a suitable average that fully accounts for
      the first-order optics of a set of optical systems. It proposes an average based
      on ray transferences and logarithms and exponentials of matrices. Application to
      eyes in particular is discussed.

PMID- 15491487
TI  - Macular pigment optical density in young Chinese adults.
AB  - PURPOSE: The purpose of this study was to determine the macular pigment optical
      density (MPOD) in a group of Chinese subjects using a simple customized light
      emitting diode-based device. METHODS: Heterochromatic flicker photometry was used
      in this study. With a 1 degrees diameter circular test stimulus, MPOD was
      estimated by comparing the relative sensitivities to a blue light, against a
      green reference, between foveal and parafoveal 4 degrees temporal locations.
      Fixed alternating frequencies were used. Repeatability was determined on a small
      group of subjects. A further group of 67 young healthy subjects provided data for
      MPOD norms. RESULTS: All results were corrected to the common MPOD reference
      wavelength of 460 nm. The group-averaged MPOD was 0.48 (S.D. 0.23). We found no
      gender difference in MPOD. The coefficient of variability was 7.2-8.0% and the
      coefficient of repeatability was 0.12. CONCLUSIONS: The MPOD of Chinese subjects
      did not differ greatly from the reported MPOD in white subjects.

PMID- 15491488
TI  - Reliability, normative data, and the effect of age-related macular disease on the
      Eger Macular Stressometer photostress recovery time.
AB  - PURPOSE: To assess repeatability and reproducibility, to determine normative
      data, and to investigate the effect of age-related macular disease, compared with
      normals, on photostress recovery time measured using the Eger Macular
      Stressometer (EMS). METHOD: The study population comprised 49 healthy eyes of 49
      participants. Four EMS measurements were taken in two sessions separated by 1 h
      by two practitioners, with reversal of order in the second session. EMS readings
      were also taken from 17 age-related maculopathy (ARM), and 12 age-related macular
      degeneration (AMD), affected eyes. RESULTS: EMS readings are repeatable to within
      +/-7 s. There is a statistically significant difference between controls and ARM
      affected eyes (t = 2.169, p = 0.045), and AMD affected eyes (t = 2.817, p =
      0.016). The EMS is highly specific, and demonstrates sensitivity of 29% for ARM,
      and 50% for AMD. CONCLUSIONS: The EMS may be a useful screening test for ARM,
      however, direct illumination of the macula of greater intensity and longer
      duration may yield less variable results.

PMID- 15491489
TI  - Normative contrast sensitivity values for the back-lit Melbourne Edge Test and
      the effect of visual impairment.
AB  - BACKGROUND: The Melbourne Edge Test (MET) is a portable forced-choice edge
      detection contrast sensitivity (CS) test. The original externally illuminated
      paper test has been superseded by a backlit version. The aim of this study was to
      establish normative values for age and to assess change with visual impairment.
      METHOD: The MET was administered to 168 people with normal vision (18-93 years
      old) and 93 patients with visual impairment (39-97 years old). Distance visual
      acuity (VA) was measured with a log MAR chart. RESULTS: In those eyes without
      disease, MET CS was stable until the age of 50 years (23.8 +/- 0.7 dB) after
      which it decreased at a rate of approximately 1.5 dB per decade. Compared with
      normative values, people with low vision were found to have significantly reduced
      CS, which could not be totally accounted for by reduced VA. CONCLUSIONS: The MET
      provides a quick and easy measure of CS, which highlights a reduction in visual
      function that may not be detectable using VA measurements.

PMID- 15491492
TI  - Incidence of "quasi-ditags" in catalogs generated by Serial Analysis of Gene
      Expression (SAGE).
AB  - BACKGROUND: Serial Analysis of Gene Expression (SAGE) is a functional genomic
      technique that quantitatively analyzes the cellular transcriptome. The analysis
      of SAGE libraries relies on the identification of ditags from sequencing files;
      however, the software used to examine SAGE libraries cannot distinguish between
      authentic versus false ditags ("quasi-ditags"). RESULTS: We provide examples of
      quasi-ditags that originate from cloning and sequencing artifacts (i.e. genomic
      contamination or random combinations of nucleotides) that are included in SAGE
      libraries. We have employed a mathematical model to predict the frequency of
      quasi-ditags in random nucleotide sequences, and our data show that clones
      containing less than or equal to 2 ditags (which include chromosomal cloning
      artifacts) should be excluded from the analysis of SAGE catalogs. CONCLUSIONS:
      Cloning and sequencing artifacts contaminating SAGE libraries could be eliminated
      using simple pre-screening procedure to increase the reliability of the data.

PMID- 15491493
TI  - GeneLink: a database to facilitate genetic studies of complex traits.
AB  - BACKGROUND: In contrast to gene-mapping studies of simple Mendelian disorders,
      genetic analyses of complex traits are far more challenging, and high quality
      data management systems are often critical to the success of these projects. To
      minimize the difficulties inherent in complex trait studies, we have developed
      GeneLink, a Web-accessible, password-protected Sybase database. RESULTS: GeneLink
      is a powerful tool for complex trait mapping, enabling genotypic data to be
      easily merged with pedigree and extensive phenotypic data. Specifically designed
      to facilitate large-scale (multi-center) genetic linkage or association studies,
      GeneLink securely and efficiently handles large amounts of data and provides
      additional features to facilitate data analysis by existing software packages and
      quality control. These include the ability to download chromosome-specific data
      files containing marker data in map order in various formats appropriate for
      downstream analyses (e.g., GAS and LINKAGE). Furthermore, an unlimited number of
      phenotypes (either qualitative or quantitative) can be stored and analyzed.
      Finally, GeneLink generates several quality assurance reports, including
      genotyping success rates of specified DNA samples or success and heterozygosity
      rates for specified markers. CONCLUSIONS: GeneLink has already proven an
      invaluable tool for complex trait mapping studies and is discussed primarily in
      the context of our large, multi-center study of hereditary prostate cancer (HPC).
      GeneLink is freely available at http://research.nhgri.nih.gov/genelink.

PMID- 15491494
TI  - The ProActive trial protocol - a randomised controlled trial of the efficacy of a
      family-based, domiciliary intervention programme to increase physical activity
      among individuals at high risk of diabetes [ISRCTN61323766].
AB  - BACKGROUND: Increasing prevalence of obesity and disorders associated with
      sedentary living constitute a major global public health problem. While previous
      evaluations of interventions to increase physical activity have involved
      communities or individuals with established disease, less attention has been
      given to interventions for individuals at risk of disease. METHODS/DESIGN:
      ProActive aims to evaluate the efficacy of a theoretical, evidence- and family
      based intervention programme to increase physical activity in a sedentary
      population, defined as being at-risk through having a parental family history of
      diabetes. Primary care diabetes or family history registers were used to recruit
      365 individuals aged 30-50 years, screened for activity level. Participants were
      assigned by central randomisation to three intervention programmes: brief written
      advice (comparison group), or a psychologically based behavioural change
      programme, delivered either by telephone (distance group) or face-to-face in the
      family home over one year. The protocol-driven intervention programme is
      delivered by trained facilitators, and aims to support increases in physical
      activity through the introduction and facilitation of a range of self-regulatory
      skills (e.g. goal setting). The primary outcome is daytime energy expenditure and
      its ratio to resting energy expenditure, measured at baseline and one year using
      individually calibrated heart rate monitoring. Secondary measures include self
      report of individual and family activity, psychological mediators of behaviour
      change, physiological and biochemical correlates, acceptability, and costs,
      measured at baseline, six months and one year. The primary intention to treat
      analysis will compare groups at one-year post randomisation. Estimation of the
      impact on diabetes incidence will be modelled using data from a parallel ten-year
      cohort study using similar measures. DISCUSSION: ProActive is the first efficacy
      trial of an intervention programme to promote physical activity in a defined high
      risk group accessible through primary care. The intervention programme is based
      on psychological theory and evidence; it introduces and facilitates the use of
      self-regulatory skills to support behaviour change and maintenance. The trial
      addresses a range of methodological weaknesses in the field by careful
      specification and quality assurance of the intervention programme, precise
      characterisation of participants, year-long follow-up and objective measurement
      of physical activity. Due to report in 2005, ProActive will provide estimates of
      the extent to which this approach could assist at-risk groups who could benefit
      from changes in behaviours affecting health, and inform future pragmatic trials.

PMID- 15491496
TI  - Toxoplasma and coxiella infection and psychiatric morbidity: a retrospective
      cohort analysis.
AB  - BACKGROUND: It has been suggested that infection with Toxoplasma gondii is
      associated with slow reaction and poor concentration, whilst infection with
      Coxiella burnetii may lead to persistent symptoms of fatigue. METHODS: 425
      farmers completed the Revised Clinical Interview Schedule (CIS-R) by computer
      between March and July 1999 to assess psychiatric morbidity. Samples of venous
      blood had been previously collected and seroprevalence of T. gondii and C.
      burnetii was assessed. RESULTS: 45% of the cohort were seropositive for T. gondii
      and 31% were positive for C. burnetii. Infection with either agent was not
      associated with symptoms reflecting clinically relevant levels of concentration
      difficulties, fatigue, depression, depressive ideas or overall psychiatric
      morbidity. CONCLUSIONS: We do not provide any evidence that infection with
      Toxoplasma gondii or Coxiella burnetii is associated with neuropsychiatric
      morbidity, in particular with symptoms of poor concentration or fatigue. However,
      this is a relatively healthy cohort with few individuals reporting
      neuropsychiatric morbidity and therefore the statistical power to test the study
      hypotheses is limited.

PMID- 15491495
TI  - Association of house spraying with suppressed levels of drug resistance in
      Zimbabwe.
AB  - BACKGROUND: Public health strategies are needed to curb antimalarial drug
      resistance. Theoretical argument points to an association between malaria
      transmission and drug resistance although field evidence remains limited. Field
      observations, made in Zimbabwe, on the relationship between transmission and
      multigenic drug resistance, typified by chloroquine, are reported here. METHODS:
      Periodic assessments of the therapeutic response of uncomplicated falciparum
      malaria to chloroquine in two selectively sprayed or unsprayed health centre
      catchments, from 1995 - 2003. Cross-sectional analysis of in vivo chloroquine
      failure events for five sites in relation to natural endemicity and spraying
      history. RESULTS: During selective house spraying, the chloroquine failure rate
      for the sprayed catchment decreased, such that, after four years, the odds of
      chloroquine failure were 4x lower than before start of spraying in the area (OR
      0.2, 95% CI 0.07 - 0.75, p = 0.010, n = 100). Chloroquine failure odds for the
      sprayed area became 4x lower than contemporaneous failure odds for the unsprayed
      area (OR 0.2 95% CI 0.08 - 0.65, p = 0.003, n = 156), although the likelihood of
      failure was not significantly different for the two catchments before selective
      spraying started (OR 0.5, 95% CI 0.21 - 1.32; p = 0.170, n = 88). When spraying
      ended, in 1999, the drug failure odds for the former sprayed area increased back
      4 fold by 2003 (OR 4.2, 95%CI 1.49 - 11.78, p = 0.004, n = 146). High altitude
      areas with naturally lower transmission exhibited a 6x lower likelihood of drug
      failure than low-lying areas (OR 0.16 95% CI 0.068 - 0.353, -2 log likelihood
      change 23.239, p < 0.001, n = 465). Compared to sites under ongoing annual
      spraying, areas that were last sprayed 3-7 years ago experienced a 4-fold higher
      probability of chloroquine failure (OR 4.1, 95%CI 1.84 - 9.14, -2 log likelihood
      change 13.956, p < 0.001). CONCLUSION: Reduced transmission is associated with
      suppressed levels of resistance to chloroquine and presumably other regimens with
      multigenic drug resistance. It seems the adoption of transmission control
      alongside combination chemotherapy is a potent strategy for the future
      containment of drug-resistant malaria.

PMID- 15491497
TI  - Inter-residue distances derived from fold contact propensities correlate with
      evolutionary substitution costs.
AB  - BACKGROUND: The wealth of information on protein structure has led to a variety
      of statistical analyses of the role played by individual amino acid types in the
      protein fold. In particular, the contact propensities between the various amino
      acids can be converted into folding energies that have proved useful in structure
      prediction. The present study addresses the relationship of protein folding
      propensities to the evolutionary relationship between residues. RESULTS: The
      contact preferences of residue types observed in a representative sample of
      protein structures are converted into a residue similarity matrix or inter
      residue distance matrix. Remarkably, these distances correlate excellently with
      evolutionary substitution costs. Residue vectors are derived from the distance
      matrix. The residue vectors give a concrete picture of the grouping of residues
      into families sharing properties crucial for protein folding. CONCLUSIONS: Inter
      residue distances have proved useful in showing the explicit relationship between
      contact preferences and evolutionary substitution rates. It is proposed that the
      distance matrix derived from structural analysis may be useful in aligning
      proteins where remote homologs share structural features. Residue vectors derived
      from the distance matrix illustrate the spatial arrangement of residues and point
      to ways in which they can be grouped.

PMID- 15491498
TI  - Serum adiponectin as a biomarker for in vivo PPARgamma activation and PPARgamma
      agonist-induced efficacy on insulin sensitization/lipid lowering in rats.
AB  - BACKGROUND: PPARgamma agonists ameliorate insulin resistance and dyslipidemia in
      type 2 diabetic patients. Adiponectin possesses insulin sensitizing properties,
      and predicts insulin sensitivity of both glucose and lipid metabolism. In diet
      induced insulin resistant rats and ZDF rats, the current studies determined the
      correlation between PPARgamma agonist-upregulated fatty acid binding
      protein(FABP3) mRNA in adipose tissue and PPARgamma agonist-elevated serum
      adiponectin, and the correlation between PPARgamma agonist-elevated serum
      adiponectin and PPARgamma agonist-mediated efficacy in insulin sensitization and
      lipid lowering. RESULTS: Parallel groups of SD rats were fed a high fat/sucrose
      (HF) diet for 4 weeks. These rats were orally treated for the later 2 weeks with
      vehicle, either PPARgamma agonist GI262570 (0.2-100 mg/kg, Q.D.), or GW347845 (3
      mg/kg, B.I.D). Rats on HF diet showed significant increases in postprandial serum
      triglycerides, free fatty acids (FFA), insulin, and area under curve (AUC) of
      serum insulin during an oral glucose tolerance test, but showed no change in
      serum glucose, adiponectin, and glucose AUC. Treatment with GI262570 dose
      dependently upregulated adipose FABP3 mRNA, and increased serum adiponectin.
      There was a position correlation between adipose FABP3 mRNA and serum adiponectin
      (r = 0.7350, p < 0.01). GI262570 dose-dependently decreased the diet-induced
      elevations in triglycerides, FFA, insulin, and insulin AUC. Treatment with
      GW347845 had similar effects on serum adiponectin and the diet-induced
      elevations. There were negative correlations for adiponectin versus
      triglycerides, FFA, insulin, and insulin AUC (For GI262570, r = -0.7486, -0.4581,
      -0.4379, and -0.3258 respectively, all p < 0.05. For GW347845, r = -0.6370, 
      0.6877, -0.5512, and -0.3812 respectively, all p < 0.05). In ZDF rats treated
      with PPARgamma agonists pioglitazone (3-30 mg/kg, B.I.D.) or GW347845 (3 mg/kg,
      B.I.D.), there were also negative correlations for serum adiponectin versus
      glucose, triglycerides, FFA (for pioglitazone, r = -0.7005, -0.8603, and -0.9288
      respectively; for GW347845, r = -0.9721, -0.8483, and -0.9453 respectively, all p
      < 0.01). CONCLUSIONS: This study demonstrated that (a) PPARgamma agonists
      improved insulin sensitivity and ameliorated dyslipidemia in HF fed rats and ZDF
      rats, which were correlated with serum adiponectin; (b) Serum adiponectin was
      positively correlated with adipose FABP3 mRNA in GI262570-treated rats. These
      data suggest that serum adiponectin can serve as a biomarker for both in vivo
      PPARgamma activation and PPARgamma agonist-induced efficacy on insulin resistance
      and dyslipidemia in rats.

PMID- 15491499
TI  - Information assessment on predicting protein-protein interactions.
AB  - BACKGROUND: Identifying protein-protein interactions is fundamental for
      understanding the molecular machinery of the cell. Proteome-wide studies of
      protein-protein interactions are of significant value, but the high-throughput
      experimental technologies suffer from high rates of both false positive and false
      negative predictions. In addition to high-throughput experimental data, many
      diverse types of genomic data can help predict protein-protein interactions, such
      as mRNA expression, localization, essentiality, and functional annotation.
      Evaluations of the information contributions from different evidences help to
      establish more parsimonious models with comparable or better prediction accuracy,
      and to obtain biological insights of the relationships between protein-protein
      interactions and other genomic information. RESULTS: Our assessment is based on
      the genomic features used in a Bayesian network approach to predict protein
      protein interactions genome-wide in yeast. In the special case, when one does not
      have any missing information about any of the features, our analysis shows that
      there is a larger information contribution from the functional-classification
      than from expression correlations or essentiality. We also show that in this case
      alternative models, such as logistic regression and random forest, may be more
      effective than Bayesian networks for predicting interactions. CONCLUSIONS: In the
      restricted problem posed by the complete-information subset, we identified that
      the MIPS and Gene Ontology (GO) functional similarity datasets as the dominating
      information contributors for predicting the protein-protein interactions under
      the framework proposed by Jansen et al. Random forests based on the MIPS and GO
      information alone can give highly accurate classifications. In this particular
      subset of complete information, adding other genomic data does little for
      improving predictions. We also found that the data discretizations used in the
      Bayesian methods decreased classification performance.

PMID- 15491500
TI  - Parents' reported preference scores for childhood atopic dermatitis disease
      states.
AB  - BACKGROUND: We sought to elicit preference weights from parents for health states
      corresponding to children with various levels of severity of atopic dermatitis.
      We also evaluated the hypothesis that parents with children who had been
      diagnosed with atopic dermatitis would assign different preferences to the health
      state scenarios compared with parents who did not have a child with atopic
      dermatitis. METHODS: Subjects were parents of children aged 3 months to 18 years.
      The sample was derived from the General Panel, Mommies Sub-Panel, and Chronic
      Illness Sub-Panel of Harris Interactive. Participants rated health scenarios for
      atopic dermatitis, asthma, and eyeglasses on a visual analog scale, imagining a
      child was experiencing the described state. RESULTS: A total of 3539 parents
      completed the survey. Twenty-nine percent had a child with a history of atopic
      dermatitis. Mean preference scores for atopic dermatitis were as follows: mild,
      91 (95% confidence interval [CI], 90.7 to 91.5); mild/moderate, 84 (95%CI, 83.5
      to 84.4); moderate, 73 (95%CI, 72.5 to 73.6); moderate/severe, 61 (95%CI, 60.6 to
      61.8); severe, 49 (95% CI, 48.7 to 50.1); asthma, 58 (95%CI, 57.4 to 58.8); and
      eyeglasses, 87(95%CI, 86.3 to 87.4). CONCLUSIONS: Parents perceive that atopic
      dermatitis has a negative effect on quality of life that increases with disease
      severity. Estimates of parents' preferences can provide physicians with insight
      into the value that parents place on their children's treatment and can be used
      to evaluate new medical therapies for atopic dermatitis.

PMID- 15491502
TI  - Effect of splenectomy on type-1/type-2 cytokine gene expression in a patient with
      adult idiopathic thrombocytopenic purpura (ITP).
AB  - BACKGROUND: In view of clinical observations and laboratory results that support
      a central role of the spleen in idiopathic thrombocytopenic purpura (ITP)
      pathophysiology, we studied the effect of splenectomy on type-1 and type-2
      cytokine gene expression in an adult ITP case, refractory to conservative
      treatment. CASE PRESENTATION: The patient was subjected to splenectomy 9 months
      after the diagnosis with complete response, attaining platelet counts over 150 x
      106/L within 10 days after the operation. Two consecutive blood samples were
      obtained from the patient, 3 and 7 months after the splenectomy for the purposes
      of this study. A control group consisted of 11 healthy adults. Peripheral blood
      mononuclear cells were prepared from each blood sample and cultured in vitro for
      8 h with the addition of the mitogens phorbol myristate acetate and ionomycin.
      Total cellular RNA extracted from 106 cells was submitted to semiquantitave
      reverse transcriptase-polymerase chain reaction (RT-PCR) for the amplification of
      IL-2, IFN-gamma, IL-4, IL-5, and IL-10 metagraphs. The PCR products were run on
      ethidium-stained agarose gels, photographed and quantified by densitometry.A
      steep decrease of type-1 cytokine expression (IL-2, IFN-gamma) and their
      calculated sum expressing Th1 activity was observed at 7 months post-splenectomy
      compared to 3 months post-splenectomy, in parallel with a rise of platelet count
      from 190 x 106/L to 265 x 106/L. The change of type-2 cytokine expression (IL-4,
      IL-5, IL-10) was slight and the Th2 activity (IL-4+IL-5) remained largely
      unchanged. The Th1/Th2 ratio, that reflects the pathogenic disease-specific T
      cell immune deviation, was accordingly reduced 7 months post-splenectomy (Th1/Th2
      = 1.3) compared to 3 months (Th1/Th2 = 3.5). CONCLUSIONS: The reduction of the
      Th1/Th2 cytokine ratio that was observed over time after splenectomy was
      accompanied by full clinical remission. Nevertheless, the persistence of a type-1
      polarization, even after several months following spleen removal, is suggestive
      of a more basic abnormality of the immune function in these patients.

PMID- 15491501
TI  - Effect of granulocyte colony-stimulating factor in experimental methicillin
      resistant Staphylococcus aureus sepsis.
AB  - BACKGROUND: Methicillin resistant Staphylococcus aureus (MRSA) is the leading
      pathogenic cause of nosocomial infections, especially in bacteraemia and sepsis.
      The essential therapy for MRSA infection is glycopeptides. Therapeutic failure
      can be seen with this therapy and the mortality is still high. The aim of this
      study was to evaluate the additional effect of G-CSF on the traditional
      antibiotic treatment in an experimental MRSA sepsis. METHODS: Experimental sepsis
      was performed in mice by intraperitoneal injection of MRSA isolate. Inoculum dose
      was estimated as 6 x 10(9)ml. Mice were randomised for the study into four group;
      control group (not receive any therapy), G-CSF group (1000 ng/daily,
      subcutaneously for 3 d), antibiotic group (vancomycin 25 or 50 mg/kg
      intraperitoneally every 12 hours for 7 d), and vancomycin+G-CSF group (at the
      same concentrations and duration). Autopsy was done within one hour after mice
      died. If mice was still alive at the end of seventh day, they were sacrificed,
      and autopsy was done. In all groups, the effect of G-CSF therapy on the survival,
      the number of the MRSA colonies in the lung, liver, heart, spleen, and peritoneal
      cultures, the histopathology of the lung, liver, heart and spleen was
      investigated. RESULTS: One hundred and six mice were used. There were no
      significant differences in survival rates and bacterial eradication in G-CSF
      group compared with control group, and also in antibiotic +G-CSF group compared
      with antibiotic alone group. These parameters were all significantly different in
      antibiotic alone group compared with control group. Histopathologically,
      inflammation of the lung and liver were significantly reduced in vancomycin (25
      mg/kg)+G-CSF and vancomycin (50 mg/kg)+G-CSF subgroups, respectively (p < 0.01).
      The histopathological inflammation of the other organs was not significantly
      different in antibiotic+G-CSF group compared with antibiotic group and, also G
      CSF group compared with control group. CONCLUSION: G-CSF treatment had no
      additional effect on survival and bacterial eradication in MRSA sepsis in
      nonneutropenic mice; and only a little effect on histopathology. G-CSF treatment
      is very expensive, likewise glycopeptides. The more interest in infection control
      measures, and prevent the spread of MRSA infections is more rational.

PMID- 15491503
TI  - Gastric T-cell lymphoma associated with hemophagocytic syndrome.
AB  - BACKGROUND: Lymphoma-associated hemophagocytic syndrome (LAHS) occurs in mostly
      extra nodal non-Hodgkin's lymphoma. LAHS arising from gastrointestinal lymphoma
      has never been reported. Here we report a case of gastric T-cell lymphoma
      associated hemophagocytic syndrome. CASE PRESENTATION: A 51-year-old woman
      presented with pain, redness of breasts, fever and hematemesis. Hematological
      examination revealed anemia. Gastroscopy revealed small bleeding ulcers in the
      stomach and the computed tomography scan showed liver tumor. She underwent total
      gastrectomy for gastrointestinal bleeding and the histopathology revealed gastric
      T-cell lymphoma. She continued to bleed from the anastomosis and died on the 8th
      postoperative day. Autopsy revealed it to be a LAHS. CONCLUSIONS: If
      Hemophagocytic syndrome (HPS) occurs in lymphoma of the gastrointestinal tract,
      bleeding from the primary lesion might be uncontrollable. Early diagnosis and
      appropriate treatment are needed for long-term survival.

PMID- 15491504
TI  - The central role of Fas-ligand cell signaling in inflammatory lung diseases.
AB  - Following inflammation and injury in the lung, loss of epithelial cell precursors
      could determine the balance between tissue regeneration and fibrosis. This review
      discusses evidence that proapoptotic Fas-Fas ligand (FasL) signaling plays a
      central role in pulmonary inflammation, injury and fibrosis. FasL signaling
      induces inflammatory apoptosis in epithelial cells and alveolar macrophages, with
      concomitant IL-1 beta and chemokine release, leading to neutrophil infiltration.
      FasL signaling plays a critical role in models of acute lung injury, idiopathic
      pulmonary fibrosis and silicosis; blockade of Fas-FasL interactions either
      prevents or attenuates pulmonary inflammation and fibrosis. Serologic and
      immunohistochemical studies in patients support a major pathogenic role of Fas
      and FasL molecules in inflammatory lung diseases. Identification of the
      pathogenic role of FasL could facilitate the discovery of more effective
      treatments for currently untreatable inflammatory lung diseases.

PMID- 15491505
TI  - The involvement of endothelial progenitor cells in tumor angiogenesis.
AB  - Endothelial progenitor cells (EPCs) have been isolated from peripheral blood
      CD34, VEGFR-2, or AC 133 (CD133) antigen-positive cells, which may home to site
      of neovascularization and differentiate into endothelial cells in situ.
      Endothelial cells contribute to tumor angiogenesis, and can originate from
      sprouting or co-option of neighbouring pre-existing vessels. Emerging evidence
      indicate that bone marrow-derived circulating EPCs can contribute to tumor
      angiogenesis and growth of certain tumors. This review article will summarize the
      literature data concerning this new role played by EPCs in tumor angiogenesis.

PMID- 15491506
TI  - Adult mesenchymal stem cells: characterization, differentiation, and application
      in cell and gene therapy.
AB  - A considerable amount of retrospective data is available that describes putative
      mesenchymal stem cells (MSCs). However, there is still very little knowledge
      available that documents the properties of a MSC in its native environment.
      Although the precise identity of MSCs remains a challenge, further understanding
      of their biological properties will be greatly advanced by analyzing the
      mechanisms that govern their self-renewal and differentiation potential. This
      review begins with the current state of knowledge on the biology of MSCs,
      specifically with respect to their existence in the adult organism and
      postulation of their biological niche. While MSCs are considered suitable
      candidates for cell-based strategies owing to their intrinsic capacity to self
      renew and differentiate, there is currently little information available
      regarding the molecular mechanisms that govern their stem cell potential. We
      propose here a model for the regulation of MSC differentiation, and recent
      findings regarding the regulation of MSC differentiation are discussed. Current
      research efforts focused on elucidating the mechanisms regulating MSC
      differentiation should facilitate the design of optimal in vitro culture
      conditions to enhance their clinical utility cell and gene therapy.

PMID- 15491507
TI  - Immunomodulatory benefits of cyclosporine A in inflammatory bowel disease.
AB  - Etiopathogenesis of mucosal inflammation in inflammatory bowel disease remains a
      complex and enigmatic field; various factors (genetic, environmental and
      microbial) trigger an event that activates intestinal immune and nonimmune
      systems culminating in inflammation and tissue injury. Specifically, both innate
      and adaptive immune systems seem to play important roles in the pathophysiology
      of this disease. Cyclosporine A represents a macrolide immune modulator with
      primary inhibitory effects on T helper lymphocyte production of interleukin-2,
      and other cytokines leading to altered T-lymphocyte and B-lymphocyte function.
      The diversity of its therapeutic outcome reported in inflammatory bowel disease
      may be due to the intricate immuno-pathogenic profile of the disease and the
      variety of the applied dose-dependent courses of therapy. Cyclosporine A exerts
      additional actions on other components of the inflammatory infiltrate, including
      neutrophils and mast cells, thereby appearing to be a multi-dynamic therapeutic
      approach, although with potential drawbacks, that may be applied alone or
      combined with other immunomodulatory agents in inflammatory bowel disease
      patients. Because cyclosporine A induces apoptosis of T-lymphocytes responsible
      for perpetuation of the chronic inflammatory process in the disease with
      potential tumorigenic effect, it may exert a further inhibitory effect on cancer
      development in inflammatory bowel disease patients, and can be combined with
      other relative agents, such as rapamycin, which also promotes T-lymphocyte
      apoptosis. Therefore, recently established multifactorial action of cyclosporine
      A in relation to the pathogenesis of the disease can open new horizons for
      prospective, controlled trials in large cohorts, aiming to emphasize cyclosporine
      A's potential.

PMID- 15491508
TI  - Somatic stem cell research for neural repair: current evidence and emerging
      perspectives.
AB  - Recent evidence supports the existence of adult mammalian stem cell
      subpopulations, particularly within the bone marrow, that may be able to
      "transdifferentiate" across tissue lineage boundaries, thus offering an
      accessible source for therapeutic applications even for neural tissue repair.
      However, the difficulties in reproducing some experimental data, the rarity of
      the transdifferentiation events and observations that cell fusion may be an
      alternative explanation argue against the idea of stem cell plasticity.
      Investigations going beyond descriptive experiments and more mechanicistic
      approaches may provide a more solid foundation to adult stem cell therapeutic
      potential.

PMID- 15491509
TI  - Etoposide differentially affects bone marrow and dermal derived endothelial
      cells.
AB  - Chemotherapy alteration of the bone marrow microenvironment has the potential to
      influence hematopoietic recovery following transplantation. To discern the effect
      of specific drugs on components of the complex marrow microenvironment, in vitro
      models have significant utility. In the current study we sought to determine
      whether dermal (HMEC-1) and marrow derived endothelial cells (BMEC-1) respond
      differently to identical chemotherapy exposure. BMEC-1 cells were consistently
      more sensitive to etoposide exposure than HMEC-1 cells, measured as reduced
      viability. BMEC-1 also had reduced focal adhesion kinase (FAK) and VCAM-1 protein
      expression following chemotherapy, in contrast to dermal derived endothelial
      cells in which neither protein was influenced dramatically by etoposide. The two
      endothelial cell lines had markedly different levels of baseline VE-Cadherin
      protein, which was modestly altered by treatment. These data indicate that marrow
      derived endothelial cells have disruption of specific proteins following
      chemotherapy that may influence their ability to facilitate hematopoietic cell
      entry or egress from the marrow. In addition, these observations suggest that
      while BMEC-1 and HMEC-1 share a variety of characteristics, they differ
      significantly in their response to stress and should be incorporated into
      specific models with this consideration.

PMID- 15491511
TI  - Hydrolysis of myelin basic protein by polyclonal catalytic IgGs from the sera of
      patients with multiple sclerosis.
AB  - Various catalytic antibodies or abzymes have been detected recently in the sera
      of patients with several autoimmune pathologies, where their presence is most
      probably associated with autoimmunization. Recently we have shown that DNase,
      RNase, and polysaccharide-hydrolyzing activities are associated with IgGs from
      the sera of patients with multiple sclerosis (MS). Here we present evidence
      demonstrating that highly purified MS IgGs (but not Igs from the sera of healthy
      individuals) catalyze specifically hydrolysis of human myelin basic protein
      (hMBP). In contrast to many known proteases, IgGs do not hydrolyze many other
      different proteins. Specific inhibitors of acidic and thiol proteases have no
      remarkable effect on proteolytic activity of IgGs. However, specific inhibitor of
      serine (PMSF, AEBSF, and benzamidin) and metal-dependent (EDTA) proteases
      significantly inhibit activity of proteolytic abzymes. Interestingly, the ratio
      of serine-like and metal-dependent activities of MS IgGs varied very much from
      patient to patient. The findings speak in favor of the generation by the immune
      systems of individual MS patients of a variety of polyclonal anti-MBP IgGs with
      different catalytic properties.

PMID- 15491510
TI  - Double transgenic mice with type 1 diabetes mellitus develop somatic, metabolic
      and vascular disorders.
AB  - The double transgenic mice (dTg) were obtained by mating: (i) transgenic mice
      expressing the hemagglutinin of influenza virus under the insulin promoter with
      (ii) transgenic mice expressing specific T lymphocytes with receptor for the
      immunodominant epitope of the same virus. In this study we show that dTg mice
      developed type 1 diabetes mellitus associated with hyperglycemia, low level of
      plasma insulin, glucosuria, weight loss and approximately 90% mortality (at 3
      months biological age). The membrane of red blood cells was more sensitive to
      osmotic shock in diabetic mice, compared to non-diabetic mice, assessing systemic
      oxidative stress. Both vasoconstriction and vasorelaxation of the renal arteries
      decreased significantly in diabetic mice (compared to the control group of non
      diabetic mice) related to the phenotypic change of endothelium and smooth muscle
      cells within the artery wall. This animal model, may be used in developing
      various strategies to study pancreatic beta-cell function, as well as for a
      better metabolic control conducting to a reduced risk of vascular complications.

PMID- 15491512
TI  - The ultrastructural aspects of neoplastic myoepithelial cell in pleomorphic
      adenomas of salivary glands.
AB  - The purpose of this study has been to establish the major ultrastructural aspects
      of the myoepithelial cell and the myoepithelial-like cells proliferated in the
      pleomorphic adenomas of salivary glands. Thus, twelve benign pleomorphic adenomas
      of salivary glands have been studied by electron-microscopy transmission
      techniques. Our analysis has proved the proliferation of two major cellular
      populations, one of ductal type and one of myoepithelial type, which tried to
      reproduce the tubulo-acinar cytoarchitecture from the normal salivary glands. We
      have also noticed the key role of the so-called 'modified' myoepithelial cells
      from the periphery of the proliferating epithelial units in the genesis of the
      myxoid and chondromyxoid tumoral stromal areas. All these ultrastructural aspects
      have explained the great histological diversity of these salivary gland neoplasms
      as well as the key role of the myoepithelial cell in its histogenesis.

PMID- 15491513
TI  - Use of an improved zirconyl hematoxylin stain in the diagnosis of Barrett's
      esophagus.
AB  - Barrett's esophagus is a precancerous condition characterized by replacement of
      the normal stratified squamous epithelium by a simple columnar epithelium with
      goblet cells that secrete an acidic mucin. As originally formulated, fresh
      solutions of zirconyl hematoxylin stain goblet cells poorly. An improved formula,
      quintupling the amount of oxidant, yields zirconyl hematoxylin solutions that
      stain goblet cells darkly even when fresh. The improved zirconyl hematoxylin can
      be used in place of alcian blue in the diagnosis of Barrett's esophagus. The
      ingredients of zirconyl hematoxylin are always readily available and are
      generally recognized as safe.

PMID- 15491514
TI  - Vesicle traffic through intercellular bridges in DU 145 human prostate cancer
      cells.
AB  - We detected cell-to-cell communication via intercellular bridges in DU 145 human
      prostate cancer cells by fluorescence microscopy. Since DU 145 cells have
      deficient gap junctions, intercellular bridges may have a prominent role in the
      transfer of chemical signals between these cells. In culture, DU 145 cells are
      contiguous over several cell diameters through filopodial extensions, and
      directly communicate with adjacent cells across intercellular bridges. These
      structures range from 100 nm to 5 microm in diameter, and from a few microns to
      at least 50-100 microm in length. Time-lapse imagery revealed that (1) filopodia
      rapidly move at a rate of microns per minute to contact neighboring cells and (2)
      intercellular bridges are conduits for transport of membrane vesicles (1-3 microm
      in diameter) between adjacent cells. Immunofluorescence detected alpha-tubulin in
      intercellular bridges and filopodia, indicative of microtubule bundles, greater
      than a micron in diameter. The functional meaning, interrelationship of these
      membrane extensions are discussed, along with the significance of these findings
      for other culture systems such as stem cells. Potential applications of this work
      include the development of anti-cancer therapies that target intercellular
      communication and controlling formation of cancer spheroids for drug testing.

PMID- 15491515
TI  - Langerhans cell histiocytosis: report of a single organ involvement in a child.
AB  - Langerhans cell histiocytosis is a rare disorder characterized by abnormal
      proliferation of Langerhans cells that can affect various organ systems. The
      disease usually presents as a unifocal lytic bone lesion and can affect any age
      group. Less frequently it presents as a disseminated disease with multisystem
      involvement. Hepatic manifestation in Langerhans cell histiocytosis is relatively
      rare and usually presents as a part of a disseminated process. We report a case
      of Langerhans cell histiocytosis involving only the liver in a 9-years-old child.

PMID- 15491516
TI  - Apoptosis of pancreatic acinar cells in acute pancreatitis: is it good or bad?
AB  - Acute pancreatitis 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 events that regulate the severity of
      acute pancreatitis are, for the most part, unknown. Several recent studies have
      suggested that the acinar cell response to injury may be an important determinant
      of disease severity. In these studies, mild acute pancreatitis was found to be
      associated with extensive apoptotic acinar cell death while severe acute
      pancreatitis was found to involve extensive acinar cell necrosis but very little
      acinar cell apoptosis. These observations have led to the hypothesis that
      apoptosis might be a favorable response to acinar cell and that interventions
      which favor induction of apoptotic, as opposed to necrotic, acinar cell death
      might reduce the severity of an attack of acute pancreatitis. This review aims to
      discuss our current understanding of the contribution of acinar cell apoptosis to
      the severity of acute pancreatitis.

PMID- 15491517
TI  - [Patients' voice: improving understanding between doctors and patients].

PMID- 15491518
TI  - [Emergency contraception: user's profile in primary care emergency services].
AB  - OBJECTIVES: To establish the emergency contraception (EC) users profile and
      whether she perceives this type of contraception as an emergency. Design. Cross
      sectorial study (over one year period: March 2002-March 2003). SETTING: Emergency
      Services in Primary Care. Usera and Carabanchel; 11th Area; Madrid. PARTICIPANTS:
      Women requesting EC in these centres. MAIN OUTCOME MEASURES: A questionary was
      filled out for all participants with their age, how many hours had spent since
      sexual intercourse took place (within 24 h), usual method of contraception used,
      previous use of EC, level of education, and reason for this request. RESULTS: 89
      women. Drops out: 0. Average age: 23.7+/-48 years (range: 16-40 years). 79.8% of
      them came to medical emergency services in less than 24 h after sexual
      intercourse. Usual anticonceptive method was the condom (88.8%), 2.2% used
      hormones, 9% no contraceptive method at all and none of them had used the
      intrauterine device. 34.8% were previous users of EC. Education levels: 2.2% of
      women only could read and write, elementary school (37.1%), secondary school
      (34.8%) and high school (25.8%). Reasons for requesting EC: 91% condom failure,
      7.9% not to have used any contraceptive method, and 1.1% wrong use of natural
      birth control methods. Among the women who had went to the emergency services
      within the 24 h of the sexual intercourse the 77.4% of all of them had requested
      EC previously and the 93% of those had requested EC for the first time (P=.032).
      Likewise all of them with high school level and who could write and read, the
      93.9% with elementary school level, and the 71% with secondary studies went to
      the emergency services within the 24 h of the non protected sexual intercourse
      (P=.05). CONCLUSIONS: Most of the women were young, they perceived the
      unprotected sexual intercourses as an emergency, the condom was the most
      frequently used anticonceptive method, they requested EC due to condom breakage.
      In 1/3 of the cases the EC had been requested previously and this group and the
      young women with secondary studies one were who requested it later.

PMID- 15491519
TI  - [Commentary: emergency contraception: will we ever be able to standardize the
      prescription?].

PMID- 15491520
TI  - [Design and validation of the questionnaire on Women's Sexual Function (WSF)].
AB  - OBJECTIVE: To design and validate a self-administered questionnaire to evaluate
      sexual function in women. DESIGN: Cross-sectional, multi-centre study. SETTING:
      Primary care, in 9 health centres of the Community of Valencia. PARTICIPANTS:
      Women not at risk of sexual dysfunction, selected by consecutive sampling.
      Initial sample 600, valid sample 212. INTERVENTIONS: Questionnaire of 14
      questions to be filled out in 5-10 minutes, designed by a committee of experts.
      The participants filled it out on two occasions (test and retest) with an
      interval of 4 weeks. Diagnostic assessment by a committee of observers. MAIN
      MEASUREMENTS: Reliability between test and retest questions: - One to one:
      analysis of concordance: kappa index. Significant variations: 2 goodness of fit. 
      On the sum of replies: comparison of means (Wilcoxon) and subsequent analysis:
      intra-class correlation coefficient (ICC). Internal consistency: Cronbach's
      alpha. Validity of contents: consensus of experts. Inter-observer correlation:
      ICC and factor analysis. RESULTS: Reliability: one to one: Kappa from 0.597 to
      0.743. 2 not significant (ns). Between total sums (Wilcoxon), ns (z=-0.312,
      P=.755) (95% confidence). ICC: r=0.9587 (95% CI, 0.9460-0.9685), significant
      correlation (99% confidence). Internal consistency: Cronbach's alpha test:
      0.8954, retest: 0.8973. Inter-observer correlation: ICC: r=0.9498 (CI, 0.9386
      0.9611) significant (confidence 99%). Factor analysis: groupings of items 9, 13,
      14; 1, 2, 3, 10; 5, 6, 7, 8. CONCLUSIONS: The questionnaire is stable, valid and
      reliable. It evaluates the stages of sexual response, initiative and degree of
      sexual communication. It collects data on sexual performance. It is useful for
      exploring and diagnosing sexual dysfunction.

PMID- 15491521
TI  - [The elderly at risk in the province of Guadalajara].
AB  - OBJECTIVE: To study fragile elderly people in the population, their
      characteristics and their distribution according to fragility markers. DESIGN:
      Cross-sectional, descriptive study using a survey. SETTING: Primary care. Elderly
      people living in Guadalajara in January 2002. PARTICIPANTS: 434 people were
      interviewed (1.24% of population). There were 157 losses (26.6%). INTERVENTIONS:
      The questionnaire contained social and demographic variables (age, sex, setting),
      care variables (medication, pathologies, home care) and evaluative scales
      (Barthel, Folstein, Yesavage, Diaz-Palacios). MAIN MEASUREMENTS: Fragility
      markers: 3 or more pathologies, 6 or more drugs, dementia, and/or positive on one
      of the four scales used. RESULTS: Subjects lived in rural areas more (56.7%; CI,
      52-61.3), but there were not more women. Fragile elderly, n=257 (59.2%; CI, 54.6
      63.8), were more women (OR=1.8; CI, 1.5-2.2) and over 70 (OR=80-84, 5.2; CI, 3.7
      7.5; OR=85-89, 8.2; CI, 5.3-12.8). Prevalence of markers was: 3 or more
      pathologies, 30.2% (95% CI, 25.8-34.5); cognitive deterioration, 22.6% (95% CI,
      18.7-26.5); social risk, 20.8% (95% CI, 16.3-23.8); multi-medication, 18.7% (95%
      CI, 15-22.3); Barthel incapacity, 11.7 (95% CI, 8.7-14.8); depression, 5.3% (95%
      CI, 3.2-7.5); and dementia, 3.2% (95% CI, 1.6-4.9). Women suffered cognitive
      deterioration more. The over-80s suffered cognitive deterioration, social risk
      and incapacity more. CONCLUSIONS: There was high prevalence of fragility with
      cognitive deterioration, multi-medication and social risk; and lower presence of
      dementia. Women and the most elderly people were most affected.

PMID- 15491522
TI  - [Evaluation of the quality of inter-clinic documents. Does their proper filling
      out by the family doctor affect the reply obtained from the specialist?].
AB  - OBJECTIVE: To analyse the filling out of the inter-clinic form (IF) at a centre
      with special fields of care (CS) and to assess whether its proper filling out in
      primary care (PC) affects the reply from specialist care. DESIGN: Cross
      sectional, descriptive study. SETTING: Primary health care area in the Community
      of Valencia. PARTICIPANTS: Randomised sample of IFs of patients referred for the
      first time from PC to specialists. MAIN MEASUREMENTS: Evaluation criteria were
      grouped in two: those IFs were considered acceptable (IFCA) in which the family
      doctor included the reason for consultation or his/her diagnostic impression, as
      well at least one of the following: anamnesis, personal background, physical
      examination, further tests or current medication. The remaining IFs were
      considered inadequately filled out (IFCI). RESULTS: The sample analysed for the
      IF audit of the CS was 392 people. The result of the audit in the specialist
      clinics was that 243 IFs were blank (62.0%); the specialist doctor was identified
      in 19% of cases; the diagnosis was given in 23.5%; treatment, in 21%, and the
      follow-up plan, in 20%. In the PC evaluation, there were no blank IFs; anamnesis
      was recorded in 41.8%; reason for consultation in 73%; suspected diagnosis in
      58.2%, and treatment in 11.5%. The sample to analyse the differences in the
      filling of the form in specialist care according to the quality of the PC filling
      out was 529 IFs. 56.3% of the IFs were considered acceptable. No statistically
      significant differences were found in the filling of any of the criteria of
      evaluation by the specialist doctor between the IFs from PC of acceptable and
      inadequate quality, except on the question of specifying treatment. CONCLUSIONS:
      We found no relationship between the quality of the IF from PC and the reply from
      specialist care. Currently, the filling out of IFs continues to be deficient.

PMID- 15491523
TI  - [The professional career of family doctors (2nd part)].

PMID- 15491524
TI  - [On scientific principles for action: the practical idealism of family medicine].

PMID- 15491525
TI  - [Research in primary health care. Basic premises].

PMID- 15491526
TI  - [Suicide and home care: an exceptional situation?].

PMID- 15491527
TI  - [Ways that amyotrophic lateral sclerosis may present in primary care].

PMID- 15491528
TI  - [Should we run eye screening for all diabetic patients?].

PMID- 15491529
TI  - [Galactorrhea induced by lansoprazole].

PMID- 15491530
TI  - [Like anthropologists on Mars].

PMID- 15491531
TI  - [Flu vaccination during pregnancy: at present, utopian].

PMID- 15491532
TI  - [Lung function evolution and respiratory symptoms].

PMID- 15491533
TI  - [Quality of life with chronic obstructive pulmonary disease: the influence of
      level of patient care].
AB  - OBJECTIVE: The aim of the study was to determine the factors related to the
      health-related quality of life (HRQL) of patients with stable chronic obstructive
      pulmonary disease (COPD) and to assess the degree of influence of level of
      patient care (primary or specialized). MATERIAL AND METHOD: An observational
      descriptive, cross-sectional, multicenter study was carried out. The study sample
      was a randomized selection taken from a stratified sample of patients treated by
      primary care physicians and pneumologists from each Spanish region. Only those
      patients whose level of health care was indicated and whose diagnosis of COPD was
      confirmed by spirometry were enrolled in the study. RESULTS: Five hundred sixty
      patients were assessed, 100 from primary health care and 460 from pneumology
      practices. No significant differences between the 2 levels of care were found in
      the scores on the HRQL questionnaire (Spanish version of the St George's
      Respiratory Questionnaire). There was a weak correlation between patients'
      perception of health and lung function parameters. Factors related to HRQL in the
      multivariate analysis were dyspnea, the presence of COPD exacerbations in the
      previous year, consequent visits to the emergency department, age, and degree of
      airflow restriction, but not level of patient care. CONCLUSIONS: Stable COPD
      patients' HRQL is not related to their level of care, be it primary or
      specialized, but is related to other factors such as dyspnea, presence of
      exacerbations or consequent visits to the emergency department, age, and degree
      of airflow restriction.

PMID- 15491534
TI  - [Lung transplantation in rats: a viable experimental model].
AB  - OBJECTIVES: To incorporate a new fast, safe, and reversible anesthetic procedure
      into the experimental model of lung transplantation (LT) using a cuff technique
      originally described by Mizuta. MATERIAL AND METHOD: Eighty-eight Sprague-Dawley
      rats were used in the experimental model. Thirty left LTs were performed, using
      60 rats. The donor heart-lung block was excised by median sternotomy with
      dissection of the left lung and cuffs (intravenous catheters cut into 3-mm
      sections) were put in place. The left lung was implanted in the recipient by
      lateral thoracotomy using the cuffs for anastomoses. The duration of surgery and
      postoperative complications were recorded. Also noted were signs of ischemia
      reperfusion injury, and acute rejection of the transplanted lung. RESULTS: We
      discarded lungs excised from 8 animals when developing the experimental model.
      Transplants could not be completed in 10 rats due to technical problems, despite
      satisfactory excision. Of the rats who received a transplant, 4 died in the first
      24 hours and 26 survived to 48 hours. They were then killed and examined. The
      state of the anastomoses was good and signs of ischemia-reperfusion injury, as
      well as acute rejection were observed in the parenchyma of the transplanted lung.
      CONCLUSIONS: LT with cuffs in rats is a valid, reliable, reproducible, and cheap
      model for studying ischemia-reperfusion injury and rejection in LT. The surgical
      technique is complex, requiring experienced surgeons and a long learning process.
      Modification of the technique to more closely resemble the surgical procedure in
      humans is possible, thus facilitating interpretation and allowing more reliable
      extrapolation to humans.

PMID- 15491535
TI  - [Four-year results after lung volume reduction surgery for emphysema].
AB  - OBJECTIVES: While the short-term results of lung volume reduction surgery are
      known, follow-up over several years has not often been described. The purpose of
      the present study was to describe results in terms of functional improvement,
      dyspnea, quality of life, and mortality over a 4-year period in patients with
      advanced emphysema. PATIENTS AND METHODS: Fourteen successive patients were
      enrolled between 1996 and 2000 and studied prospectively for 4 years. All
      patients served as their own controls and initially received pulmonary
      rehabilitation and medication. Preoperative data were used as baseline and were
      compared to postoperative data over 4 years. The data analyzed were: functional
      improvement (forced expiratory volume in 1 second [FEV1]), quality of life,
      dyspnea, and patient loss due to death or referral to a lung transplantation
      program. RESULTS: Patients with advanced emphysema (mean FEV1 [SD]: 22.8% [11%]
      of predicted) were studied. Postoperative mortality was 14%. Overall mortality
      (postoperative plus deaths due to respiratory insufficiency) was 28% at 1 year
      and 35% at 4 years. Two patients died of cancer and 5 were referred for
      transplantation. At 3 months, FEV1 had improved more than 15% in 9 patients
      (64%); the improvement was maintained in 43% of patients at 1 year and 7% at 4
      years. Improvement in dyspnea paralleled improvement in FEV1. Overall, at 3
      months mean FEV1 had improved 41.9% (68%), transitional dyspnea index 2.7 (3),
      and quality of life questionnaire score 1 (0.9). Thus, improvements were
      considerable, but there was great variation. Preoperative mean decrease in FEV1
      was 50 (32) mL/y, and postoperative decrease 194 (70) mL/y. CONCLUSIONS: With the
      inclusion criteria used, there was considerable variation in the results.
      Significant overall functional improvement was maintained in 50% of the patients
      1 year following surgery and in 7% 4 years after surgery. Given such results,
      together with a surgical mortality rate of 14% and overall mortality of 28% in
      the first year, we believe that the criteria for using lung reduction surgery
      should be revised.

PMID- 15491536
TI  - [Human leukocyte antigens A and B in Turkish patients with sarcoidosis].
AB  - OBJECTIVE: Associations between human leukocyte antigens (HLA) and sarcoidosis
      have been reported in several studies. We aimed to investigate these associations
      in Turkish patients. PATIENTS AND METHOD: We performed HLA-A, HLA-B, HLA-C, and
      HLA-D typing in 83 patients with sarcoidosis and in 250 healthy controls using a
      microlymphocytotoxicity method to investigate genetic susceptibility to the
      disease. RESULTS: Because of significant violation of Hardy-Weinberg equilibrium
      at HLA-C and HLA-DQB1 loci, only results obtained at other HLA loci were used.
      Although HLA-A9, HLA-B5, and HLA-B8 allele frequencies were significantly higher
      in the patient group compared to the controls (odds ratio [OR]= 21.8, P= .015;
      OR= 9.34, P= .049; OR= 2.26, P= .031, respectively), none of the differences
      remained significant after applying the Bonferroni correction. HLA-A24, HLA-A26,
      and HLA-B62 alleles were significantly less frequent in the patient group
      compared to the controls (OR= 0.48, P= .018; OR= 0.19, P= .003; OR= 0.11, P=
      .044, respectively). However, the differences also failed to remain significant
      after Bonferroni correction. CONCLUSIONS: These results suggest that both HLA may
      play significant roles (either increasing or reducing risk) in the pathogenesis
      of sarcoidosis and in its distinct clinical forms and laboratory findings.

PMID- 15491537
TI  - [Active tuberculosis case finding among immigrants in Barcelona].
AB  - OBJECTIVE: To assess the prevalence of tuberculous infection and disease in
      recent economic immigrants in Barcelona. SUBJECTS AND METHOD: Examination and
      testing of immigrants. Tuberculin tests (TTs) were given and the presence of
      scars from tuberculosis vaccinations were noted. Thresholds of 5 and 15 mm were
      established for positivity in unvaccinated and vaccinated individuals,
      respectively. RESULTS: A total of 3651 persons were examined, but only 3151
      completed the study. Eighteen were diagnosed with tuberculosis (571.2 per
      100,000) and 50.6% were classified as positive TT reactors, 34.4% because of
      infection and 16.3% possibly because of tuberculosis vaccination. The percentage
      of reactors was significantly higher in the sample of economic immigrants than in
      the local population. Age, male sex, place of origin, greater poverty, and higher
      prevalence of disease in the country of origin were associated with tuberculous
      infection in the sample. DISCUSSION: Active case finding proved efficient.
      Interference from tuberculosis vaccination greatly affects the findings,
      depending on the positivity threshold that is established. We recommend that
      chest radiographs be used in addition to TTs. Immigration will change the nature
      of endemic tuberculosis in Spain, and strategies should be specifically designed
      to deal with the new challenges that will appear.

PMID- 15491538
TI  - [Altitude, the ratio of PaO2 to fraction of inspired oxygen, and shunt: impact on
      the assessment of acute lung injury].
AB  - The ratio of PaO2 to the fraction of inspired oxygen (PaO2/FIO2) is commonly used
      to determine the severity of acute lung injury and acute respiratory distress
      syndrome (ARDS). The research presented here used computational models of the
      lung to analyze the effect of altitude on the PaO2/FIO2 ratio and pulmonary
      shunt. At a given shunt, the PaO2/FIO2 ratio is lower at higher altitudes.
      Therefore, when evaluating for ARDS based on a PaO2/FIO2 ratio of <200 mm Hg,
      patients residing at high altitudes will have less shunt and, presumably, less
      severe lung injury than patients at sea level. This should be taken into
      consideration when comparing patients from different altitudes. Shunt should more
      often be measured directly or be estimated assuming a constant arteriovenous
      oxygen content difference.

PMID- 15491539
TI  - [Pulmonary tuberculosis as an occupational disease].

PMID- 15491540
TI  - [Octreotide for conservative management of postoperative chylothorax].
AB  - Postoperative chylothorax after lung resection is a major problem leading to
      morbidity and mortality and requiring reoperation in a large number of cases. The
      most advisable and least aggressive option is conservative management in
      progressive stages: a diet rich in medium-chain fatty acids and/or total
      parenteral nutrition, in addition to chest tube drainage. Including octreotide in
      this regimen seems to be related to a higher success rate without the need for
      surgery. We report a case in which the effectiveness and safety of octreotide in
      the resolution of postoperative chylothorax was excellent.

PMID- 15491541
TI  - [Recurrent pneumothorax due to rheumatoid arthritis].

PMID- 15491542
TI  - Brugia malayi infection in Meriones unguiculatus: antibody response to
      recombinant BmR1.
AB  - BmR1 recombinant antigen has previously been shown to demonstrate high
      sensitivity and specificity in the serological diagnosis of brugian filariasis in
      humans. In this study, the pattern of recognition of antibody to BmR1 during
      Brugia malayi infection was investigated by employing Meriones unguiculatus as
      the experimental model. Thirty two gerbils were infected subcutaneously with 120
      L(3); and two control groups each comprising 25 animals were employed. ELISA
      using BmR1 was used to detect filaria-specific IgG antibodies elicited by the
      gerbils; using sera collected from the day 1 until day 150 post-inoculation
      (p.i.). The results showed that BmR1 detected B. malayi infection in gerbils
      harboring adult worms irrespective of the presence of circulating microfilaria,
      and was exemplified by positive ELISA results in nine a microfilaraemic animals
      that harbored live adult worms. The initial time of the antibody recognition was
      at day 8 p.i. and the antibody titre showed some correlation with adult worm
      burden.

PMID- 15491543
TI  - Entamoeba histolytica: cDNAs cloned as 30kDa collagen-binding proteins (CBP)
      belong to an antioxidant molecule family. Protection of hamsters from amoebic
      liver abscess by immunization with recombinant CBP.
AB  - A cDNA expression library of Entamoeba histolytica was screened with antiserum to
      native amoebic collagen binding proteins (CBPs), and two clones C13 and C7 which
      partially encode for the 30 kDa CBP were obtained. The sequenced clones were 90%
      homologous. C7 had a 69 bp deletion at the 5' end that is present in C13 and
      encodes for a Glu-Cys-Lys rich region and a four amino acids repeat (Glu-Lys-Glu
      Cys). Purified fusion proteins from these cDNA clones were able to bind native
      type I collagen gels in a pH, calcium, ionic strength, and temperature dependent
      way. The binding of pgtC13 to collagen gel was time and temperature stable, while
      pgtC7 binding was not, suggesting that the deleted region in C7 is important for
      the binding. The clones reported here partially encode a 30 kDa CBP that also
      belong to an antioxidant molecule family. We demonstrated that the fusion protein
      pgtC13 is immunogenic and partially protective as a subunit vaccine in the
      hamster model of amoebic liver abscess.

PMID- 15491544
TI  - Wolbachia infection in the newly described Ecuadorian sand flea, Tunga
      trimamillata.
AB  - Wolbachia pipientis is an intracellular endosymbiont producing reproductive
      alterations in its hosts. This bacterium have been reported in many arthropods
      and nematodes. By PCR amplification and sequencing of the 16S rDNA and ftsZ genes
      we have identified a Wolbachia strain in the newly described sand-flea, Tunga
      trimamillata. Prevalence of this endosymbiont in the 26 individuals screened is
      equal to 35%. Sympatric and allopatric specimens of the related species Tunga
      penetrans were also analysed, but in contrast to literature data, Wolbachia
      appears absent in the presently analysed 24 specimens. Field studies evidence a
      female-biased sex-ratio in T. trimamillata, suggesting that Wolbachia may cause
      sex-ratio distortion in this species. By means of BLAST search and phylogenetic
      analysis we found that the Wolbachia strain from T. trimamillata pertains to the
      arthropod-infecting Wolbachia; this strain is highly differentiated from the
      Wolbachia strain of T. penetrans described in literature.

PMID- 15491545
TI  - Lack of correlation between in vitro susceptibility to Benznidazole and
      phylogenetic diversity of Trypanosoma cruzi, the agent of Chagas disease.
AB  - Chagas disease remains an important health problem in Central and South America.
      Nitroimidazole derivative drugs like Benznidazole are commonly used to treat
      Trypanosoma cruzi infection. Natural variation of drug susceptibility between
      various T. cruzi stocks has been proposed as a possible explanation of treatment
      failure. Thus, the aim of this work was to determine potential correlations
      between in vitro Benznidazole susceptibility of different T. cruzi stocks and
      their genetic diversity. For this purpose, 16 natural stocks representing the
      overall genetic diversity of the parasite were analysed. Genetic characterisation
      was assessed by both random amplified polymorphic DNA (RAPD) and multilocus
      enzyme electrophoresis (MLEE) analyses. Drug activity was determined by two
      complementary methods, the MTT-PMS micro-method and FACs analysis. The 50%
      inhibitory concentrations (IC(50)s) were determined. Important variation of
      IC(50) values (7.3-16.9 microM) among stocks belonging to different discrete
      typing units (DTUs) was recorded. Further, correlation analysis showed that
      natural susceptibility to Benznidazole in T. cruzi expressed as IC(50) level was
      not related with its genetic structure represented by the different DTUs. These
      results are discussed in relation with the proposed hypothesis establishing a
      link between genetic diversity and biological behaviour in T. cruzi.

PMID- 15491546
TI  - Hepatobiliary changes, antibody response, and alteration of liver enzymes in
      hamsters re-infected with Opisthorchis viverrini.
AB  - We investigated pathological changes, antibody response, and liver enzymes in
      hamsters re-infected with Opisthorchis viverrini. Group 1 received a single dose
      of 50 metacercariae; Groups 2 and 3 were first dosed with of 30 metacercariae and
      re-infected with 20 more once or twice at three month intervals. Inflammation and
      liver cell necrosis were observed on 3D (day 3) for Group 3 and 7D for Group 2 in
      comparison with 21D for Group 1. Pathological changes included peri-ductal
      fibrosis, bile duct dilation, and small bile duct formation. Increased O.
      viverrini-specific IgG levels ranked in the order Group 3>Group 2>Group 1. Liver
      enzyme activity was related to inflammatory cell infiltration. Re-infection
      induced faster inflammation and more severe pathological changes in association
      with parasite-specific antibody during chronic inflammation. This study
      emphasizes that there is an important relationship between the gradual decreases
      of inflammation with a concomitant increase in fibrosis after re-infection.

PMID- 15491547
TI  - Toxoplasma gondii: isolation of tachyzoites rhoptries and incorporation into
      Iscom.
AB  - Rhoptries have been isolated from Toxoplasma gondii tachyzoites by subcellular
      fractionation in isopynic density sucrose gradient. Five bands were observed, and
      transmission electron microscopy of these indicated that rhoptries were in band
      3. This band had a density of 1.17 g/cm(3). Fraction 1 had membrane structures of
      the parasite. Fraction 2 contained membranes and mitochondria. Fraction 4 had
      mostly conoid structure and fraction 5 showed ghosts. The electrophoretic and
      Western blotting analysis of the fractions indicated the presence of a number of
      proteins. Iscoms were constructed from band 3, which contained the rhoptry
      structures. Iscom showed a only protein incorporated of 55 kDa. Isolation of the
      parasite organelles has got in this work is necessary to identification,
      characterization, and function elucidation of the organelle proteins.

PMID- 15491548
TI  - Plasmodium falciparum: production of human antibodies specific for the MSP-3
      protein in the Hu-SPL-SCID mouse.
AB  - Human immunity against Plasmodium falciparum malaria is mediated by IgG
      antibodies. One of the major targets of protective antibodies is the MSP-3
      protein. Anti-MSP-3 human monoclonal antibodies could therefore be valuable for
      passive immunotherapy, particularly of drug resistant malaria. Human monoclonal
      antibodies were previously produced in the Hu-SPL-SCID model reconstituted with
      human splenocytes, immunized by highly immunogenic neo-antigen or a recall
      antigen. We report here that this model can also be successfully employed to
      induce human antibody-secreting cells specific of low immunogenicity neo
      antigens, such as MSP-3. These cells represent a new and valuable source of human
      monoclonal anti-malaria antibodies.

PMID- 15491549
TI  - Acanthocheilonema viteae: octopamine and its physiological role.
AB  - Octopamine acts as an important neurotransmitter and neuromodulator in
      arthropods, mollusks, and nematodes. In mammals, however, no definite function
      for this amine has yet been described. By virtue of this difference in the
      neurophysiological requirement of the mammalian host and nematodes, octopamine
      offers good opportunity for exploring this area deeply with a view to identify a
      unique target for filarial chemotherapy. Results of the present study indicated
      that Acanthocheilonema viteae, the rodent filarial parasite, utilized tyrosine as
      a precursor for producing octopamine and some other biogenic amines. Octopamine
      exhibited specific saturable binding with the membrane prepared from the anterior
      portion of the filariid. This amine induced concentration dependent increase in
      the membrane potential which possibly caused tonic paralysis of the filariid. The
      rate of micro filarial release by the female worms also declined in the presence
      of this amine. The study thus provided preliminary evidences for the presence of
      an octopamine neurotransmitter system and also about some of the roles it plays
      in A. viteae.

PMID- 15491550
TI  - Leishmania (Viannia): genetic analysis of cutaneous and mucosal strains isolated
      from the same patient.
AB  - Ten pairs of Leishmania (Viannia) strains isolated from mucosal and cutaneous
      lesions of the same patient were analyzed genotypically in order to determine
      whether populations that had metastasized to mucosal sites differed from those in
      the cutaneous lesion. The strains were previously characterized by multi locus
      enzyme electrophoresis and/or monoclonal antibodies reactivity, and, for this
      study, only isolates from the same patient which were identified as the same
      species were employed. PCR-RFLP of internal transcribed spacer (ITS) rDNA, random
      amplified polymorphic DNA (RAPD), and schizodeme analyses were conducted. All
      genotyping methods revealed microheterogeneity between cutaneous and mucosal
      isolates from the same patient. The PCR-RFLP of the ITS rDNA and RAPD analysis
      were numerically analyzed through similarity coefficients and dendrograms were
      generated. All phenograms clustered cutaneous and mucosal strains of the same
      patient in one branch with a high degree of similarity, and phenetic analysis
      matched between them. Schizodeme analysis revealed differences between strains
      that composed some pairs. Genetic analyses indicate that some populations that
      metastasize to mucosal sites are distinguishable from the population in cutaneous
      lesions, however, other approaches will be required to associate genetic
      polymorphisms with the cutaneous or mucosal phenotype of strains.

PMID- 15491551
TI  - Fate of GFP-expressing Escherichia coli in the midgut and response to ingestion
      in a tick, Ornithodoros moubata (Acari: Argasidae).
AB  - Ticks are well-known vectors of various pathogens but migration of the pathogens
      in the tick midgut is not fully understood. In the present study, the fate of
      microbes in the midgut of Ornithodoros moubata was observed using green
      fluorescent protein (GFP)-expressing Escherichia coli. Fluctuations in the
      percentage of hemocytes in the hemolymph (Hc) and expression of an antimicrobial
      peptide, defensin, in the midgut was also investigated. Most E. coli gradually
      disappeared in the midgut after ingestion fluctuations in Hc coincided with the
      changes. Expression of defensin was also confirmed and slightly up-regulated
      after E. coli ingestion. Moreover, it was demonstrated that E. coli can not pass
      through the tick midgut epithelium after ingestion by the hemolymph cultures. It
      is known that various pathogens and host immunoglobulins ingested with a blood
      meal can enter into the hemocoel, which suggests the presence of unique and
      complex passage mechanisms for each molecule and organism. The results obtained
      here help to clarify that digestion enzymes is an important function of the tick
      midgut to protect against invading molecules and organisms.

PMID- 15491552
TI  - Plasmodium falciparum: modified medium composition supports continuous
      cultivation with foetal bovine serum.

PMID- 15491553
TI  - The Echinococcus granulosus antigen B shows a high degree of genetic variability.
AB  - Echinococcus granulosus larvae secret a polymeric lipoprotein known as antigen B
      (AgB) into the metacestode hydatid fluid. Three similar AgB subunits have been
      previously identified (AgB1, AgB2, and AgB3), and their respective genes
      isolated, but the actual number of genes encoding AgB subunits remains uncertain.
      In this study, we characterize the variability of genes encoding the AgB2
      subunit, using PCR and RT-PCR followed by cloning and sequencing. We have
      analyzed 32 cDNA and 34 genomic sequences from a single metacestode, showing a
      high degree of sequence polymorphism. In addition, we have identified a possibly
      new AgB subunit, which we call AgB4. Additionally, we describe an AgB2 genomic
      clone lacking (i) a segment corresponding to the intron and (ii) a short, 45 bp
      sequence within exon II. The 45 bp segment encompasses the conserved splicing
      signals and corresponds to a highly conserved insect promoter motif.

PMID- 15491554
TI  - Cesarean section intraoperative blood loss and mode of placental separation.
AB  - OBJECTIVE: To investigate whether manual removal of the placenta is associated
      with significant blood loss compared with spontaneous separation of the placenta
      during cesarean delivery. DESIGN: A randomized prospective study of 400 women
      with normal pregnancies undergoing cesarean delivery at King Abdulaziz University
      Hospital, Jeddah, Saudi Arabia. Patients were randomly assigned to the study
      group, (manual placental removal, n=200) or the control group (spontaneous
      placental separation, n=200). Operative blood loss was assessed by the volumetric
      and gravimetric methods. Hemoglobin levels were evaluated the third postoperative
      day and patient's postoperative complications were recorded. RESULTS: The mean+/
      S.D. amount of blood loss associated with manual and spontaneous removal of the
      placenta was 713+/-240 and 669+/-253 ml, respectively. This difference was
      statistically significant (P=0.04). There was a postoperative decrease in
      hemoglobin levels in both groups. Preoperative hemoglobin levels were 11.6+/-3
      g/dl in the study group and 11.2+/-1.1 g/dl in the control group, and the
      difference was statistically significant (P=0.006). The postoperative hemoglobin
      levels at day 3 were 9.0+/-1.2 g/dl in the study group and 9.9+/-1.2 g/dl in the
      control group (P=0.003), also a statistically significant difference. The
      incidence of endometritis, wound infection, and need for blood transfusion was
      similar in the two groups. CONCLUSION: Manual delivery of the placenta was
      significantly associated with greater operative blood loss and greater decrease
      in postoperative hemoglobin levels, but with shorter operative time compared with
      spontaneous placental separation. No difference in postoperative complications
      was noted between the groups.

PMID- 15491555
TI  - A non-inflatable anti-shock garment for obstetric hemorrhage.
AB  - OBJECTIVES: Maternal death from hemorrhage in low resource settings is frequently
      due to long delays in transportation to referral centers and/or in obtaining
      blood and surgical interventions. This case series was designed to demonstrate
      the feasibility, efficacy and safety of the non-inflatable anti-shock garment (NI
      ASG) for resuscitation and hemostasis in the initial management of obstetric
      hemorrhage and shock. METHODS: Fourteen cases of obstetric hemorrhage and
      hypovolemic shock at Memorial Christian Hospital, Sialkot, Pakistan were managed
      with a specific clinical protocol based on using NI-ASG as the primary
      intervention. RESULTS: The NI-ASG was used to resuscitate and stabilize women
      with hypovolemic shock from 18 to 57 h. Thirteen patients survived without
      evidence of morbidity, but one had prolonged shock followed by multiple organ
      failure and death. CONCLUSIONS: This study confirmed that the NI-ASG quickly
      restored the vital signs of most women in severe hemorrhagic shock and stabilized
      them while awaiting blood transfusion.

PMID- 15491556
TI  - Proinflammatory cytokines and other indications of inflammation in cervico
      vaginal secretions and preterm delivery.
AB  - OBJECTIVES: To compare the usefulness of evaluating cervico-vaginal
      concentrations of proinflammatory cytokines (interleukin [IL]-1alpha, IL-1beta,
      IL-6 and IL-8) and procalcitonin (PCT), as well as serum levels of C-reactive
      protein (CRP), leucocytosis and band form granulocytes in the prediction of
      preterm delivery (PTD). METHODS: A total of 65 pregnant women experiencing
      preterm labor (PTL) were enrolled in the study. Concentrations of the studied
      markers in women who delivered prematurely and in women who, after treatment,
      delivered at term were compared. Receiver operator characteristic (ROC) curve
      analysis was used for all study parameters. RESULTS: Cervico-vaginal IL-6 and
      procalcitonin as well as serum CRP concentrations were higher in women who
      delivered prematurely than in those who delivered near term. A cervico-vaginal IL
      6 level greater than 660 pg/ml was the best predictive value of preterm delivery
      (sensitivity, 50%; specificity 90%; positive predictive value [PPV], 85%; NPV,
      62%; likelihood ratio, 5.17). Moreover, the area under the ROC curve of 0.75 for
      cervico-vaginal IL-6 was greater than for other markers. CONCLUSION: Although
      cervico-vaginal concentrations of procalcitonin and serum concentration of CRP
      are higher in women who deliver prematurely, only cervico-vaginal concentration
      of IL-6 is a good predictor of preterm delivery.

PMID- 15491557
TI  - Persistent HPV infection in postmenopausal age women.
AB  - OBJECTIVE: Persistence of human papillomavirus (HPV) is associated with an
      increased risk of developing cervical SIL and cancer in young women. Because this
      association in older, postmenopausal age women has received little attention, we
      evaluated persistence of HPV among women in this age group. METHODS: Women
      (n=105) ages 45-64 were examined annually for 7 years to evaluate HPV in cervical
      cytologic specimens. PCR, dot blot hybridization and DNA sequencing were used to
      detect HPV types. RESULTS: The cumulative prevalence of HPV was 34%, and 24% had
      HPV high-risk oncogenic types which are associated with genital cancers. The most
      common oncogenic types were HPV-16 (72%) and HPV-31 (16%). The persistence rate
      of HPV infection was 16%. No specific risk factors were associated with repeat
      viral positivity. CONCLUSION: Postmenopausal women are infected with persistent
      oncogenic HPV at a substantial rate, supporting the need for continued screening
      in postmenopausal women to detect preneoplastic genital lesions.

PMID- 15491558
TI  - Medical treatment of missed abortion using misoprostol.
AB  - OBJECTIVE: To compare the efficacy of two routes of misoprostol administration
      (oral and vaginal) for treatment of missed abortion. METHODS: Two hundred women
      with confirmed missed abortion received 800 mcg misoprostol either orally or
      vaginally. All women returned for follow-up care 2 days later. If the pregnancy
      was not completely evacuated at this time, women could wait an additional 5 days
      or undergo immediate surgical completion. Efficacy was defined as the percent of
      women discharged from the study without need for surgical intervention. RESULTS:
      Efficacy was high in both groups and not statistically different (oral=89.0%,
      vaginal=92.9%). While the groups did not differ in terms of the completion rate
      by day 2 (oral=41.6%, vaginal=52.7%), the mean time to expulsion was longer
      (21.04 h) in the oral group than the vaginal group (13.47 h), p=0.041. Women in
      both groups were highly satisfied with the method. CONCLUSIONS: Medical
      management of missed abortion with either oral or vaginal misoprostol is highly
      effective and highly acceptable.

PMID- 15491559
TI  - Fetal nucleated red blood cells in maternal peripheral blood and gestational age.

PMID- 15491560
TI  - High vaginal swab cultures in normal and preterm labor.

PMID- 15491561
TI  - Lead contamination among pregnant Brazilian women living near a lead smelter.

PMID- 15491562
TI  - Magnesium sulfate regimens for eclampsia.

PMID- 15491563
TI  - Pudendal nerve block for pain relief in episiotomy repair.

PMID- 15491565
TI  - Induction of labor with misoprostol in grand multiparous patients.

PMID- 15491564
TI  - Outcome of a routine ultrasound screening program in a tertiary center in
      Australia.

PMID- 15491566
TI  - Sterilization at cesarean section in Nigeria.

PMID- 15491567
TI  - Risk factors in relation to eclampsia in Nepal.

PMID- 15491568
TI  - Gestational age and prevalence of preterm birth after vaginal metronidazole
      treatment during pregnancy.

PMID- 15491569
TI  - Postpartum ovarian vein thrombosis with positive lupus anticoagulant.

PMID- 15491570
TI  - Elevated plasma homocysteine levels in preeclampsia and eclampsia.

PMID- 15491571
TI  - Endometriosis of the colon and rectum mimicking colon cancer.

PMID- 15491572
TI  - Double uterus associated with renal aplasia; magnetic resonance appearance and
      three-dimensional computed tomographic urogram.

PMID- 15491573
TI  - Spontaneous abortion through the bladder.

PMID- 15491574
TI  - Increased risk for medical abortion failure for multiparous women.

PMID- 15491575
TI  - Intravaginal misoprostol for pregnancy termination.

PMID- 15491576
TI  - Recombinant factor VIIa after amniotic fluid embolism and disseminated
      intravascular coagulopathy.
AB  - This case report illustrates the successful use of activated recombinant factor
      VIIa in the management of severe postpartum hemorrhage secondary to amniotic
      fluid embolism.

PMID- 15491577
TI  - Severe acute maternal morbidity in rural South Africa.
AB  - OBJECTIVE: Our objective was to identify the frequency, causes, and avoidable
      factors of severe acute maternal morbidity (SAMM) in four non-specialist
      hospitals in rural South Africa. METHOD: We conducted a prospective audit using
      criteria for SAMM suited to the diagnostic and treatment facilities available in
      the primary hospital setting. For each case of SAMM, a local audit team assessed
      the standard of care against local management guidelines and examined avoidable
      factors. An external specialist also retrospectively examined avoidable factors.
      RESULT: The facility-based incidence of SAMM was 541 cases per 100,000 births
      (95% CI 368-767). The commonest organ systems involved were cerebral (42%),
      coagulation (19%), and vascular dysfunctions (16%). The commonest obstetric
      diagnoses were eclampsia (39%) and obstetric haemorrhage (32%). Approximately 65%
      of cases were avoidable. CONCLUSION: A qualitative case review audit of SAMM in a
      non-specialist rural setting appears feasible and sustainable, and provides
      valuable information towards improving deficiencies in maternal care.

PMID- 15491579
TI  - Hypertensive disorders of pregnancy.
AB  - OBJECTIVES: This study was undertaken to determine the prevalence of hypertensive
      disorders of pregnancy and evaluate their effects on the mothers and fetuses at
      Jahrom, a city in southern Iran. METHODS: A retrospective survey was performed on
      2300 pregnant women who had referred to Shahid Motahhari Hospital of Jahrom
      School of Medical Sciences from 22 September 2002 to 21 September 2003. Diagnosis
      of hypertensive disorders of pregnancy and their probable complications were made
      according to medical recording files. RESULTS: Among the studied patients, 3.3%
      were diagnosed as having hypertensive disorders of pregnancy, of which 96% were
      cases of preeclampsia/eclampsia or transient hypertension. In hypertensive
      patients, the overall maternal mortality rate was 1.3 per 10,000 and perinatal
      mortality rate was 53 per 1000 births. Low birth weight neonates were observed in
      20% of cases. CONCLUSION: Hypertensive disorders of pregnancy commonly complicate
      pregnancy and have great influences on maternal and neonatal morbidity and
      mortality rates and more attention and precision is needed to evaluate the
      pregnant women for detecting and preventing the complications.

PMID- 15491578
TI  - Mifepristone versus the Yuzpe regimen (PC4) for emergency contraception.
AB  - OBJECTIVE: To compare side effects, women's acceptance and satisfaction with
      mifepristone (100 mg) versus the Yuzpe regimen for emergency contraception (EC).
      METHODS: A total of 1000 women requesting EC within 72 h of unprotected
      intercourse were randomized to receive mifepristone 100 mg or the standard Yuzpe
      regimen. Outcome measures included patient acceptability and satisfaction.
      RESULTS: A total of 620 (62%) questionnaires were returned, 64% in the
      mifepristone group and 60% in the Yuzpe group. Mifepristone was better tolerated
      than the Yuzpe regimen. The rates of nausea (P<0.0001), abdominal pain (P=0.001),
      tiredness (P<0.0001), lethargy (P=0.001), hot flushes (P<0.0001) and dizziness
      (P<0.0001) were all significantly higher in women given the Yuzpe regimen
      compared to those who received mifepristone. Of these 94% and 80% in the
      mifepristone and Yuzpe groups, respectively, were satisfied with treatment
      (P<0.0001). Of women in the mifepristone group, 56% (181/321) had used the Yuzpe
      regimen of EC in the past and of these, 93.6% (161/172) indicated they would use
      mifepristone in the future. A total of four women in the Yuzpe group had
      mifepristone in the past and all four said they would use mifepristone in the
      future. CONCLUSION: Mifepristone has high patient acceptability and few side
      effects compared to the standard Yuzpe regimen for EC.

PMID- 15491580
TI  - Repeat induced abortions and contraceptive practices among unmarried young women
      seeking an abortion in China.
AB  - OBJECTIVE: To determine the rates of repeated abortion and contraceptive use
      among unmarried young women seeking an abortion in China. METHODS: We used an
      anonymous self-administered questionnaire at abortion clinics in Beijing,
      Changsha, and Dalian from January to September 2000. RESULTS: Of 4547 unmarried
      young women seeking an abortion, 33.0% reported having had one previous induced
      abortion. Of those who had had more than one abortion, only 29.7% used a
      contraceptive method at their first sexual intercourse after the procedure; and
      of the 446 women who chose contraception, 41.3% used the traditional methods of
      withdrawal or rhythm. Although 65.0% of the young women had used condoms at least
      once, only 9.6% did so consistently and correctly; 47.7% of the current
      pregnancies were associated with nonuse of any contraceptive, and 52.3% were
      related to contraceptive failure. CONCLUSION: The rate of unmarried young women
      seeking repeated abortions was high in China on 2000. The rate of consistent
      condom use was low, and the rate of contraceptive failure was higher.

PMID- 15491581
TI  - Skilled birth attendant competence: an initial assessment in four countries, and
      implications for the Safe Motherhood movement.
AB  - OBJECTIVES: Percentage of deliveries assisted by a skilled birth attendant (SBA)
      has become a proxy indicator for reducing maternal mortality in developing
      countries, but there is little data on SBA competence. Our objective was to
      evaluate the competence of health professionals who typically attend hospital and
      clinic-based births in Benin, Ecuador, Jamaica, and Rwanda. METHODS: We measured
      competence against World Health Organization's (WHO) Integrated Management of
      Pregnancy and Childbirth guidelines. To evaluate knowledge, we used a 49-question
      multiple-choice test covering seven clinical areas. To evaluate skill, we had
      participants perform five different procedures on anatomical models. The 166
      participants came from facilities at all levels of care in their respective
      countries. RESULTS: On average, providers answered 55.8% of the knowledge
      questions correctly and performed 48.2% of the skills steps correctly. Scores
      differed somewhat by country, provider type, and subtopic. CONCLUSION: A wide gap
      exists between current evidence-based standards and current levels of provider
      competence.

PMID- 15491582
TI  - Monitoring drug efficacy and early detection of drug resistance in human soil
      transmitted nematodes: a pressing public health agenda for helminth control.
AB  - Control of soil-transmitted helminth infection and elimination of lymphatic
      filariasis by periodic chemotherapy increase drug pressure for possible
      occurrence of resistance against single dose anthelminthics. In veterinary
      practice, frequent treatment of closed populations has led to a serious problem
      of anthelminthic drug resistance which is now largely irreversible. Reduced
      efficacy of single dose drugs against nematodes of humans should be taken as
      early warnings to tackle the issue in due time. Research and development of
      sensitive tools for monitoring and early detection of drug resistance is urgently
      needed to sustain the benefits of helminth control programs gained so far. A
      concerted action with international partners and the creation of a network of
      scientists to address this issue is the next pressing public health issue for
      helminth control.

PMID- 15491583
TI  - Nucleic acid binding properties of SmZF1, a zinc finger protein of Schistosoma
      mansoni.
AB  - During its life cycle, the flat worm Schistosoma mansoni is exposed to diverse
      environmental conditions and changes its morphological form. Each change calls
      for distinct patterns of gene expression. In order to understand the regulation
      of gene expression, it is necessary to identify regulatory elements in the
      promoter region of genes, and DNA transacting factors that control transcription.
      Zinc finger protein domains are responsible for transcription regulation of
      diverse genes in a wide range of organisms and are also involved in the promotion
      of protein-protein interactions. A transcript homologous to zinc finger gene
      sequences was isolated from a S. mansoni adult worm cDNA library and named SmZF1.
      It codes for a protein of 164 amino acids presenting three C(2)H(2) type zinc
      finger motifs. The recombinant SmZF1 protein was expressed and used on
      electrophoretic mobility shift assays to investigate the binding specificity of
      SmZF1 for DNA and RNA oligonucleotides. Our results demonstrated that SmZF1 binds
      both ds and ss DNA oligonucleotides, with an apparent preference for the specific
      D1-3DNA oligonucleotide, and also binds RNA oligonucleotides with lower affinity.
      Although we found that SmZF1 recognises DNA and RNA oligonucleotides not
      containing putative target sites, SmZF1 binds preferentially to sequence specific
      sites. Furthermore, unrelated oligonucleotides are not able to abolish this
      interaction. In silico studies identified putative SmZF1 binding sites in the
      complete genome of three model organisms and in partial genome sequences of S.
      mansoni. Six Drosophila genes presented these binding sites in their promoter
      region, indicating that they might be controlled by transcription factors
      containing zinc fingers motifs. Taken together, these results suggest that SmZF1
      acts as a putative transcription factor of S. mansoni.

PMID- 15491584
TI  - Blocked stomodeal valve of the insect vector: similar mechanism of transmission
      in two trypanosomatid models.
AB  - The regurgitation of metacyclic stages from the sand fly cardia is thought to be
      the prevailing mechanism of Leishmania transmission. This regurgitation may
      result through damage of the stomodeal valve and its mechanical block by the
      parasites. We found this phenomenon in three sand fly-Leishmania models and also
      in avian trypanosomes transmitted by Culex mosquitoes. Phlebotomus duboscqi,
      Phlebotomus papatasi, Lutzomyia longipalpis, and Culex pipiens were membrane-fed
      on blood containing Leishmania major, Leishmania chagasi (syn. infantum) and an
      unidentified avian Trypanosoma from Trypanosoma corvi clade, respectively.
      Females with the late-stage infections were processed for the optical and
      transmission electron microscopy. Localization of the parasites and changes to
      the stomodeal valve were in some aspects similar in all vector-parasite pairs
      studied: (i) a large plug of flagellates was observed in cardia region, (ii)
      parasites were attached to the chitin lining of the stomodeal valve by the
      formation of zonal hemidesmosome-like plaques. Leishmania promastigotes were
      found both attached to the valve as well as unattached in the lumen of midgut.
      The stomodeal valve of infected sand flies was opened, its chitin lining was
      destroyed and the unique filamentous structures on the apical end of cylindrical
      cells were degraded. In the Culex-Trypanosoma model, the whole population of
      epimastigotes was found in close contact with the chitin lining, and degenerative
      changes of the valve were less pronounced. We suggest that the phenomenon
      involving a blocked valve facilitating the regurgitation of parasites into the
      vertebrate host may occur generally in heteroxenous trypanosomatids transmitted
      by the bite of nematoceran Diptera.

PMID- 15491585
TI  - Babesia bigemina sexual stages are induced in vitro and are specifically
      recognized by antibodies in the midgut of infected Boophilus microplus ticks.
AB  - Babesia bigemina, a causative agent of bovine babesiosis, is transmitted from one
      bovine to another only by infected ticks. The life cycle of B. bigemina includes
      a sexual phase in the tick host; however, molecules from sexual stages of any
      Babesia species have not been characterized. This is the first report of the
      induction of sexual stages of any Babesia species in vitro, free of tick
      antigens. Intraerythrocytic parasites were cultured in vitro for 20h using an
      induction medium. Extraerythrocytic parasites were first seen 3h post induction;
      elongated stages with long projections appeared at 6h post induction and by 9h
      they paired and fused to form larger stages. Round zygotes appeared 20h post
      induction. Moreover, by using Percoll gradients, sexual stages were purified free
      of contaminating intraerythrocytic stages. Purified parasites were used to
      generate polyclonal antibodies, which specifically bound to antigens expressed in
      sexual stages induced in vitro, but not to antigens expressed in
      intraerythrocytic stages. Importantly, these antibodies specifically identified
      sexual stages from midguts of female Boophilus microplus ticks fed on infected
      cattle.

PMID- 15491586
TI  - Cytokine response profiles predict species-specific infection patterns in human
      GI nematodes.
AB  - This study investigated associations between pre-treatment cytokine expression
      and infection patterns, before and after de-worming, in humans exposed to two
      gastrointestinal nematode species. Quantitative measures of Ascaris lumbricoides
      and Trichuris trichiura infection (based on faecal egg counts) were estimated
      immediately before and 8-9 months after treatment in a Cameroonian population.
      Whole blood cytokine responses to parasite-derived antigens were assayed
      immediately pre-treatment. An overall measure of the tendency towards species
      specific infection (increasing with A. lumbricoides faecal egg counts and
      decreasing with T. trichiura faecal egg counts) was significantly positively
      related to IL-10 levels in older (14-57 year) hosts. There was a significant
      negative influence of IL-5 on reinfection probability in T. trichiura but not A.
      lumbricoides. This effect coincided with reduced reinfection success in T.
      trichiura compared to A. lumbricoides. T(H)2 cytokine expression by younger hosts
      (4-13 year) was negatively associated with contemporary A. lumbricoides faecal
      egg counts before treatment. Following treatment, the pre-treatment T(H)2
      cytokine expression data for younger hosts (now reflecting responsiveness 8-9
      months in the past) were negatively associated with T. trichiura faecal egg
      counts. Taken together, these observations suggest a successional interaction
      between T(H)2-driven immune responses and species infection over time. However,
      any differential effects of the measured immune responses on species-specific
      recruitment, maturation and mortality were superimposed upon (and outweighed by)
      the effects of other factors favouring coinfection.

PMID- 15491587
TI  - Identification of a novel mitogen-activated protein kinase in Toxoplasma gondii.
AB  - Toxoplasma gondii is an Apicomplexan parasite causing significant morbidity and
      mortality in immunocompromised hosts. Mitogen activated protein kinases regulate
      diverse biologic processes including proliferation, differentiation, survival and
      stress responses. We searched a new T. gondii genomic database to identify a 1.6
      kilobase pair (kbp) coding region with features suggesting a mitogen activated
      protein kinase. This gene is predicted to encode a 58kDa protein with a
      threonine, aspartic acid, tyrosine (TDY) activation loop, similar to parasite and
      plant mitogen activated protein kinases, but distinct from mammalian mitogen
      activated protein kinases (with threonine, glycine, tyrosine (TGY) motifs). The
      predicted protein shares 45% amino acid identity with human stress-activated
      p38alpha mitogen activated protein kinase. Expression of the cloned gene in
      Escherichia coli produced a protein with an apparent molecular weight of 63kDa
      and which exhibited kinase activity. Following osmotic stress, the abundance of
      the mRNA encoding this T. gondii mitogen activated protein kinase, which we name
      TgMAPK-1, increased in tachyzoites. Its expression rescued hog1-deficient yeast
      grown under osmotic stress. These data confirm that the gene product is a stress
      response mitogen activated protein kinase. Upon conversion of T. gondii
      tachyzoites to the latent bradyzoite form in vitro, tgMAPK-1 transcript
      accumulation increased, suggesting a role in parasite proliferation or stage
      differentiation. We previously demonstrated that pyridinylimidazole p38 mitogen
      activated protein kinase inhibitors block T. gondii replication. These inhibitors
      also blocked TgMAPK-1 autophosphorylation, suggesting that TgMAPK-1, or other
      parasite mitogen activated protein kinases are novel drug development targets.

PMID- 15491588
TI  - GRA9, a new Toxoplasma gondii dense granule protein associated with the
      intravacuolar network of tubular membranes.
AB  - Important components of the parasitophorous vacuole in which the intracellular
      protozoan parasite Toxoplasma gondii develops, comprise proteins secreted from
      apicomplexan specific secretory organelles named the dense granules. Here, we
      confirm by immunofluorescence and by cryo-electron microscopy that the recently
      isolated B10 protein (318 amino acids, 41kDa) is a new dense granule protein that
      should now be referred to as GRA9. Within the vacuolar compartment, GRA9, like
      GRA2, GRA4 and GRA6, associates with the network of tubular membranes connected
      to the parasitophorous vacuole delimiting membrane. Like the other GRA proteins,
      GRA9 is secreted into the vacuole from the anterior end of the parasite. However,
      unlike GRA2 or GRA6, GRA9 does not transit by the posterior invaginated pocket of
      the parasite where the network first assembles. Within the dense granules, GRA9
      exists in both a soluble and an insoluble state. Like the other GRA proteins,
      GRA9 is secreted as a soluble form only and like most of the GRA proteins, two
      forms of GRA9 of the similar molecular weight are detected within the vacuolar
      space: a soluble form and a membrane associated form. The dual properties of GRA9
      are not only ascribed by the presence of amphipathic and hydrophobic alpha
      helices but also by the fact that the protein is mainly hydrophilic.

PMID- 15491590
TI  - Redescription of Besnoitia tarandi (Protozoa: Apicomplexa) from the reindeer
      (Rangifer tarandus).
AB  - Besnoitia tarandi tissue cysts were found in naturally-infected reindeer
      (Rangifer tarandus) from Finland. Infectivity of its tissue cysts, bradyzoites,
      and tachyzoites to animals and cell culture was studied. The bradyzoites and
      tissue cysts were not infectious to out-bred mice, rabbits or gerbils. When fed
      tissue cysts, neither cats nor dogs excreted oocysts. However, the parasite was
      lethal to interferon-gamma gene knock out mice irrespective of the route of
      inoculation. The parasite was grown successfully in African Green Monkey cells
      from tissues of two reindeer for the first time. Non-dividing, uninucleate
      tachyzoites from smears from cell cultures were 5.6 x 1.4 microm (4.5-7.4 x 1.0
      1.9, n=50) in size. Longitudinally-cut bradyzoites in tissue sections measured
      7.4 x 1.3 microm (6.5-7.8 x 1.0-1.6, n=30). Ultrastructurally, tachyzoites and
      bradyzoites were similar to those in other Besnoitia species, and in particular
      to parasites described from cattle (Besnoitia besnoiti) and equids (Besnoitia
      bennetti) 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. tarandi 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
      Collection.

PMID- 15491591
TI  - Relationships between parasite abundance and the taxonomic distance among a
      parasite's host species: an example with fleas parasitic on small mammals.
AB  - Opportunistic parasite species, capable of exploiting several different host
      species, do not achieve the same abundance on all these hosts. Parasites achieve
      maximum abundance on their principal host species, and lower abundances on their
      auxiliary host species. Taxonomic relatedness between the principal and auxiliary
      host species may determine what abundance a parasite can achieve on its auxiliary
      hosts, as relatedness should reflect similarities among host species in
      ecological, physiological and/or immunological characters. We tested this
      hypothesis with fleas (Siphonaptera) parasitic on small Holarctic mammals. We
      determined whether the abundance of a flea in its auxiliary hosts decreases with
      increasing taxonomic distance of these hosts from the principal host. Using data
      on 106 flea species from 23 regions, for a total of 194 flea-locality
      combinations, we found consistent support for this relationship, both within and
      across regions, and even after controlling for the potentially confounding effect
      of flea phylogeny. These results are most likely explained by a decrease in the
      efficiency of the parasite's evasive mechanisms against the host's behavioural
      and immune defences with increasing taxonomic distance from the principal host.
      Our findings suggest that host switching over evolutionary time may be severely
      constrained by the coupling of parasite success with the relatedness between new
      hosts and the original host.

PMID- 15491592
TI  - Endectocide exchanges between grazing cattle after pour-on administration of
      doramectin, ivermectin and moxidectin.
AB  - Self-licking behaviour in cattle has recently been identified as a determinant of
      the kinetic disposition of topically-administered ivermectin. In the present
      study, we document the occurrence and extent of transfer between cattle of three
      topically-administered endectocides, as a consequence of allo-licking. Four
      groups of two Holstein cows each received one pour-on formulation of doramectin,
      ivermectin, or moxidectin, or no treatment. The cows were then kept together in a
      paddock. Systemic exposure to each topically-administered endectocide was
      observed in at least five of six non-treated cattle. Plasma and faecal drug
      concentration profiles in non-treated animals were highly variable between
      animals and within an animal, and sometimes attained those observed in treated
      animals. Drug exchanges were quantified by measuring plasma and faecal clearances
      after simultaneous i.v. administration of the three drugs as a cocktail. Plasma
      clearances were 185+/-43, 347+/-77 and 636+/-130ml/kg/day, faecal clearances
      representing 75+/-26, 28+/-13, and 39+/-30% of the plasma clearance for
      doramectin, ivermectin and moxidectin, respectively. The amount of drug ingested
      by non-treated cattle attained 1.3-21.3% (doramectin), 1.3-16.1% (ivermectin),
      2.4-10.6% (moxidectin) of a pour-on dose (500 microg/kg). The total amount of
      drug ingested by all non-treated cattle represented 29% (doramectin), 19%
      (ivermectin), and 8.6% (moxidectin) of the total amount of each drug poured on
      the backs of treated animals. The cumulative amounts of endectocide ingested by
      each non-treated cow ranged from 1.3 to 27.4% of a pour-on dose. Oral
      bioavailability after drug ingestion due to allo-licking was 13.5+/-9.4, 17.5+/
      3.5 and 26.1+/-11.1% for doramectin, ivermectin and moxidectin, respectively. The
      extent of drug exchange demonstrated here raises concerns for drug efficacy and
      safety, emergence of drug resistance, presence of unexpectedly high residue
      levels in treated and/or untreated animals and high environmental burdens.
      Moreover, scientific and regulatory aspects of clinical and bioequivalence trials
      for topical drug administration in cattle should be explored.

PMID- 15491593
TI  - Further observations on the ultrastructure of Cystosporogenes operophterae
      (Canning, 1960) (phylum Microsporidia) parasitic in Operophtera brumata L.
      (Lepidoptera, Geometridae).
AB  - Reinvestigation of Cystosporogenes operophterae [J. Parasitol. 46 (1960) 755] by
      electron microscopy confirmed that development in host cells takes place in a
      vacuole with a single membrane at its boundary. Although ribosomes were not
      clustered on this membrane, it is hypothesised that it originates from host
      endoplasmic reticulum. The dome-shaped anchoring disc, the morphology of the
      polaroplast and the separation of the polar tube coils from the ribosome-packed
      cytoplasm are newly described details of spore structure. The polaroplast
      consists of an outer region of compact lamellae forming 'arms' surrounding an
      inner region of widely spaced lamellae. The 'arms' extends back into the region
      of an elongate nucleus. The genera Cystosporogenes and Endoreticulatus were
      differentiated by their positions in a previously obtained 16S rDNA phylogeny and
      on the new ultrastructural data.

PMID- 15491594
TI  - Vertical transmission of nucleopolyhedrovirus in the silkworm, Bombyx mori L.
AB  - Nucleopolyhedrovirus (NPV) was tested for vertical transmission in the silkworm,
      Bombyx mori. Fifth instar larvae were exposed to four different dosages of BmNPV
      (830, 1300, 1800, and 2000OBs/larva) and a dosage of about 2000OBs/larva was
      found suitable for obtaining infected adults. Histopathological studies revealed
      the infection in susceptible tissues and organs initially, and at later stages of
      infection cycles the spermatocytes and nurse cells in the young oocytes were
      infected in the larval rudiments of testis and ovary, respectively. The mating of
      infected females with uninfected males resulted in significant reduction in
      fecundity (P < 0.01) and hatching of eggs (P < 0.001) due to transovarial
      transmission of BmNPV. Mating tests of uninfected females and infected males also
      confirmed venereal transmission as there was a significant reduction in hatching
      of eggs (P < 0.01). Further, among the F1 hybrid offspring (infected female x
      uninfected male) that were infected transovarially, larval progeny died at first
      and second instar stages, whereas those infected venereally developed acute
      lethal infection late and died by the end of third and fourth instar stage. PCR
      amplification and sequencing of 473bp of immediate early-1 (ie-1) gene of BmNPV
      isolated from the viral-infected parent and the F1 offspring confirmed that the
      viral infection is vertically transmitted to the progeny.

PMID- 15491595
TI  - Occurrence of Cystosporogenes sp. (Protozoa, Microsporidia) in a multi-species
      insect production facility and its elimination from a colony of the eastern
      spruce budworm, Choristoneura fumiferana (Clem.) (Lepidoptera: Tortricidae).
AB  - We have isolated a microsporidium from a laboratory colony of the eastern spruce
      budworm, Choristoneura fumiferana (Clem.) (Lepidoptera: Tortricidae). Light and
      electron microscopic investigations showed that gross pathology and
      ultrastructure of our isolate are similar to those described for Cystosporogenes
      legeri from the European grape vine moth, Lobesia botrana. Comparative
      phylogenetic analysis of the small subunit rDNA using maximum likelihood, maximum
      parsimony, and neighbour joining distance methods revealed perfect homology with
      the C. legeri sequence. The microsporidian was infectious to other Choristoneura
      species, as well as Malacosoma disstria, Lymantria dispar, and Lambdina
      fiscellaria. Incubation of infected egg masses at 41 degrees C for 20 min
      followed by 30 min in 33% formaldehyde did not reduce disease incidence in larval
      offspring. Exposure of one or two generations to fumagillin at 6000 ppm or higher
      eliminated infection in adult moths, but also reduced colony fitness. A clean
      colony was established by conducting individual matings and selecting disease
      free offspring.

PMID- 15491596
TI  - Genetically variable nucleopolyhedroviruses isolated from spatially separate
      populations of the winter moth Operophtera brumata (Lepidoptera: Geometridae) in
      Orkney.
AB  - Here we report a lepidopteran system in which a pathogen is both abundant and
      genotypically variable. Geographically separate populations of winter moth
      (Operophtera brumata L.) were sampled in heather habitats on the Orkney Isles to
      investigate the prevalence of a pathogen, O. brumata Nucleopolyhedrovirus
      (OpbuNPV), within the natural system. Virus was recorded in 11 of the 13 winter
      moth populations sampled, with two populations suffering mortality due to virus
      at levels of 50%. The virus genome from 200 single insect isolations was
      investigated for variation using restriction endonuclease digests. Twenty-six
      variants of OpbuNPV were detected using SalI. The polyhedrin gene of the virus
      was partially sequenced, allowing the relationship between the 26 variants to be
      portrayed as a cladogram. The phylogenetic relationship between OpbuNPV and other
      known baculovirus polyhedrin gene sequences was also established. The discovery
      of virus at such high prevalence is discussed with reference to occurrence and
      genetic variation of pathogens in other lepidopteran host populations. This study
      shows encouraging results for further studies into the role of pathogens in the
      regulation of host insect populations.

PMID- 15491589
TI  - Expressed sequence tag (EST) analysis of Gregarine gametocyst development.
AB  - Gregarines are protozoan parasites of invertebrates in the phylum Apicomplexa. We
      employed an expressed sequence tag strategy in order to dissect the molecular
      processes of sexual or gametocyst development of gregarines. Expressed sequence
      tags provide a rapid way to identify genes, particularly in organisms for which
      we have very little molecular information. Analysis of approximately 1800
      expressed sequence tags from the gametocyst stage revealed highly expressed genes
      related to cell division and differentiation. Evidence was found for the role of
      degradation and recycling in gametocyst development. Numerous additional genes
      uncovered by expressed sequence tag sequencing should provide valuable tools to
      investigate gametocyst development as well as for molecular phylogenetics, and
      comparative genomics in this important group of parasites.

PMID- 15491597
TI  - First report of a trichomycete fungus (Zygomycota: Trichomycetes) inhabiting
      larvae of Simulium ochraceum sensu lato Walker (Diptera: Simuliidae) from the
      Galapagos Islands.
AB  - A collection of the larval black fly Simulium ochraceum sensu lato Walker was
      made at six lotic habitats on San Cristobal Island, Galapagos Islands, Ecuador,
      during May 2003. Sixty-eight larvae were assayed for the presence of gut fungi
      (Zygomycota: Trichomycetes). A trichomycete, designated as Smittium sp. was found
      inhabiting the hindgut of 17.6% of S. ochraceum s.l. larvae. Implications of this
      finding with respect to both host and trichomycete biogeography are discussed.

PMID- 15491598
TI  - Wolbachia effects in Drosophila melanogaster: in search of fitness benefits.
AB  - Insect endosymbionts often influence host nutrition but these effects have not
      been comprehensively investigated in Wolbachia endosymbionts that are widespread
      in insects. Using strains of Drosophila melanogaster with the wMel Wolbachia
      infection, we showed that Wolbachia did not influence adult starvation
      resistance. Wolbachia also had no effect on larval development time or the size
      of emerging adults from a low nutrition medium. While Wolbachia may influence the
      expression of heat shock proteins, we found that there was no effect on adult
      heat resistance when tested in terms of survival or virility following heat
      stress. The absence of nutrition or stress effects suggests that other processes
      maintain wMel frequencies in natural populations of Drosophila melanogaster.

PMID- 15491599
TI  - Virulence, horizontal transmission, and sublethal reproductive effects of
      Metarhizium anisopliae (Anamorphic fungi) on the German cockroach (Blattodea:
      Blattellidae).
AB  - Virulence of Metarhizium anisopliae (Metschnikoff) Sorokin strain EAMa 01/121-Su
      against the German Cockroach, Blatella germanica (L.), was determined using four
      concentrations ranging from 4.2 x 10(6) to 4.2 x 10(9) spores per milliliter. The
      LD50 value was 1.4 x 10(7) spores per milliliter (56,000 spores per cockroach)
      and LT50 values were 14.8 days and 5.3 days for 4.2 x 10(8) and 4.2 x 10(9)
      spores per milliliter, respectively. An experiment was conducted to evaluate
      whether a fungal transmission could exist among infected and healthy cockroaches.
      Percentage mortality at a ratio of 1:10 of infected to unexposed cockroaches was
      87.5% and LT50 was 12.2 days, which indicated the potential of this strain to be
      horizontally transmitted and to rapidly spread the infection in the insect
      population. The effect of a sublethal dose (ca. LD60) of M. anisopliae EAMa
      01/121-Su strain, applied topically on German cockroaches, was studied by
      reciprocal crossing. Othecal production, oothecal hatchability, and nymphal
      production declined upon exposure to M. anisopliae EAMa 01/121-Su strain. The
      mean number of oothecae laid by female was progressively and significantly
      reduced by fungal treatment from second oviposition period onwards. Oothecal
      hatch of fungally challenged females was reduced by 46-49%, oothecal viability by
      48-85%, and nymphal production by 22-35%. Only treated females showed an effect
      on oothecal production, oothecal hatch, and nymphal production, although oothecal
      hatch was also governed by treated males at a higher significance level. Our
      results on virulence and horizontal transmission of fungal conidia of M.
      anisopliae EAMa 01/121-Su strain and its sublethal reproductive effects on German
      cockroach females are discussed in terms of its potential to decrease the pest
      status of B. germanica in the short and long terms.

PMID- 15491600
TI  - In vivo dynamics of an immune response in the bumble bee Bombus terrestris.
AB  - Concepts from evolutionary ecology have recently been applied to questions of
      immune defences. However, an important but often neglected aspect is the temporal
      dynamics of the simple immune measures used in ecological studies. Here, we
      present observations for workers of the bumble bee Bombus terrestris on the
      dynamics of the phenoloxidase (PO) system, antibacterial activity, and the total
      number of haemocytes following a challenge with immune elicitors (LPS,
      Laminarin), over a time-span ranging from 1min to 14 days. The dynamics of the PO
      measurement showed a complex pattern and was correlated with haemocyte counts.
      Antibacterial activity, on the other hand, increased sharply between 2 and 24h
      post-challenge followed by a slow decrease. Surprisingly, the effects of a
      challenge lasted up to 14 days.

PMID- 15491601
TI  - Trichomycete symbiotes of Crozetia seguyi, a primitive black fly.
AB  - Crozetia is a genus of black flies endemic to the Crozet Islands in the Indian
      Ocean. No internal symbiotes were previously known from Crozetia species. We
      report two species of trichomycete symbiotes Stachylina litoralis and Smittium
      culicisoides from Crozetia seguyi. Larvae of C. seguyi were examined from three
      sites. The infection rates for St. litoralis was 10.0-33.3% (n=47) of the larvae
      and Sm. culicisoides was 46.1-85.7% (n=47). No other symbiotes were discovered.

PMID- 15491602
TI  - Entomophthoralean fungi infecting the bird cherry-oat aphid, Rhopalosiphum padi,
      feeding on its winter host bird cherry, Prunus padus.

PMID- 15491603
TI  - Oligomeric assemblies of the Escherichia coli MalT transcriptional activator
      revealed by cryo-electron microscopy and image processing.
AB  - MalT, the dedicated transcriptional activator of the maltose regulon in
      Escherichia coli, is the prototype for a family of large (approximately 100 kDa)
      transcriptional activators. MalT self-association plays a key role in recognition
      of the target promoters, which contain several MalT sites that are cooperatively
      bound by the activator. The unliganded form of MalT is monomeric. The protein
      self-associates only in the presence of both ATP (or AMP-PNP, a non-hydrolysable
      analog of ATP) and maltotriose, the inducer. Here, we report cryo-electron
      microscopy analyses of MalT multimeric forms. We show that, in the presence of
      maltotriose and AMP-PNP, MalT associates into novel, polydisperse, curved
      homopolymers. The building block, corresponding to a MalT monomer, comprises an
      outer globular domain connected by a peduncle to an inner domain that mediates
      self-association. Image analyses highlight the significant conformational
      flexibility of these polymeric forms. In the presence of a DNA fragment
      containing a MalT-controlled promoter, malPp500, MalT forms homopolymers with a
      much smaller radius of curvature and a different conformation. We propose that
      MalT binding to the target promoters involves the assembly of a MalT homo
      oligomer that is governed by the array of MalT sites present.

PMID- 15491604
TI  - An RNA polymerase mutant deficient in DNA melting facilitates study of activation
      mechanism: application to an artificial activator of transcription.
AB  - Transcription initiation is a major target for the regulation of gene expression
      in all organisms. Transcription activators can stimulate different steps in the
      initiation process including the initial binding of RNA polymerase (RNAP) to the
      promoter and a subsequent promoter-melting step. Typically, kinetic assays are
      required to determine whether an activator exerts its effect on the initial
      binding of RNAP or on the promoter-melting step. Here we take advantage of a
      mutant Escherichia coli RNAP that is deficient in promoter melting to assess the
      ability of an activator to stabilize the initial binding of RNAP to the promoter.
      For the well-characterized activator CRP, we show that this RNAP mutant can be
      used to distinguish between effects on initial binding and promoter melting;
      these results provide an independent confirmation of the results of kinetic
      analysis. We then employ the melting-deficient RNAP mutant to demonstrate an
      effect of an artificial activator of transcription on the initial binding of
      RNAP. Our findings demonstrate that a melting-deficient RNAP mutant can be used
      to trap a normally unstable intermediate in transcription initiation, thus
      providing a novel tool for probing activation mechanism.

PMID- 15491605
TI  - Conformational changes of the small ribosomal subunit during elongation factor G
      dependent tRNA-mRNA translocation.
AB  - Translocation, a coordinated movement of two tRNAs together with mRNA on the
      ribosome, is catalyzed by elongation factor G (EF-G). The reaction is accompanied
      by conformational rearrangements of the ribosome that are, as yet, not well
      characterized. Here, we analyze those rearrangements by restricting the
      conformational flexibility of the ribosome by antibiotics binding to specific
      sites of the ribosome. Paromomycin (Par), viomycin (Vio), spectinomycin (Spc),
      and hygromycin B (HygB) inhibited the tRNA-mRNA movement, while the other partial
      reactions of translocation, including the unlocking rearrangement of the ribosome
      that precedes tRNA-mRNA movement, were not affected. The functional cycle of EF
      G, i.e. binding of EF-G.GTP to the ribosome, GTP hydrolysis, Pi release, and
      dissociation of EF-G.GDP from the ribosome, was not affected either, indicating
      that EF-G turnover is not coupled directly to tRNA-mRNA movement. The inhibition
      of translocation by Par and Vio is attributed to the stabilization of tRNA
      binding in the A site, whereas Spc and HygB had a direct inhibitory effect on
      tRNA-mRNA movement. Streptomycin (Str) had essentially no effect on
      translocation, although it caused a large increase in tRNA affinity to the A
      site. These results suggest that conformational changes in the vicinity of the
      decoding region at the binding sites of Spc and HygB are important for tRNA-mRNA
      movement, whereas Str seems to stabilize a conformation of the ribosome that is
      prone to rapid translocation, thereby compensating the effect on tRNA affinity.

PMID- 15491606
TI  - Principles of RNA compaction: insights from the equilibrium folding pathway of
      the P4-P6 RNA domain in monovalent cations.
AB  - Counterions are required for RNA folding, and divalent metal ions such as Mg(2+)
      are often critical. To dissect the role of counterions, we have compared global
      and local folding of wild-type and mutant variants of P4-P6 RNA derived from the
      Tetrahymena group I ribozyme in monovalent and in divalent metal ions. A
      remarkably simple picture of the folding thermodynamics emerges. The equilibrium
      folding pathway in monovalent ions displays two phases. In the first phase, RNA
      molecules that are initially in an extended conformation enforced by charge
      charge repulsion are relaxed by electrostatic screening to a state with increased
      flexibility but without formation of long-range tertiary contacts. At higher
      concentrations of monovalent ions, a state that is nearly identical to the native
      folded state in the presence of Mg(2+) is formed, with tertiary contacts that
      involve base and backbone interactions but without the subset of interactions
      that involve specific divalent metal ion-binding sites. The folding model derived
      from these and previous results provides a robust framework for understanding the
      equilibrium and kinetic folding of RNA.

PMID- 15491607
TI  - Alternative splice variants encoding unstable protein domains exist in the human
      brain.
AB  - Alternative splicing has been recognized as a major mechanism by which protein
      diversity is increased without significantly increasing genome size in animals
      and has crucial medical implications, as many alternative splice variants are
      known to cause diseases. Despite the importance of knowing what structural
      changes alternative splicing introduces to the encoded proteins for the
      consideration of its significance, the problem has not been adequately explored.
      Therefore, we systematically examined the structures of the proteins encoded by
      the alternative splice variants in the HUGE protein database derived from long
      (>4 kb) human brain cDNAs. Limiting our analyses to reliable alternative splice
      junctions, we found alternative splice junctions to have a slight tendency to
      avoid the interior of SCOP domains and a strong statistically significant
      tendency to coincide with SCOP domain boundaries. These findings reflect the
      occurrence of some alternative splicing events that utilize protein structural
      units as a cassette. However, 50 cases were identified in which SCOP domains are
      disrupted in the middle by alternative splicing. In six of the cases, insertions
      are introduced at the molecular surface, presumably affecting protein functions,
      while in 11 of the cases alternatively spliced variants were found to encode
      pairs of stable and unstable proteins. The mRNAs encoding such unstable proteins
      are much less abundant than those encoding stable proteins and tend not to have
      corresponding mRNAs in non-primate species. We propose that most unstable
      proteins encoded by alternative splice variants lack normal functions and are an
      evolutionary dead-end.

PMID- 15491608
TI  - Optimisation of the surface electrostatics as a strategy for cold adaptation of
      uracil-DNA N-glycosylase (UNG) from Atlantic cod (Gadus morhua).
AB  - Cold-adapted enzymes are characterised by an increased catalytic efficiency and
      reduced temperature stability compared to their mesophilic counterparts. Lately,
      it has been suggested that an optimisation of the electrostatic surface potential
      is a strategy for cold adaptation for some enzymes. A visualisation of the
      electrostatic surface potential of cold-adapted uracil-DNA N-glycosylase (cUNG)
      from Atlantic cod indicates a more positively charged surface near the active
      site compared to human UNG (hUNG). In order to investigate the importance of the
      altered surface potential for the cold-adapted features of cod UNG, six mutants
      have been characterised and compared to cUNG and hUNG. The cUNG quadruple mutant
      (V171E, K185V, H250Q and H275Y) and four corresponding single mutants all
      comprise substitutions of residues present in the human enzyme. A human UNG
      mutant, E171V, comprises the equivalent residue found in cod UNG. In addition,
      crystal structures of the single mutants V171E and E171V have been determined.
      Results from the study show that a more negative electrostatic surface potential
      reduces the activity and increases the stability of cod UNG, and suggest an
      optimisation of the surface potential as a strategy for cold-adaptation of this
      enzyme. Val171 in cod UNG is especially important in this respect.

PMID- 15491609
TI  - Coincidence of cleavage sites of intron endonuclease I-TevI and critical
      sequences of the host thymidylate synthase gene.
AB  - To maximize spread of their host intron or intein, many homing endonucleases
      recognize nucleotides that code for important and conserved amino acid residues
      of the target gene. Here, we examine the cleavage requirements for I-TevI, which
      binds a stretch of thymidylate synthase (TS) DNA that codes for functionally
      critical residues in the TS active site. Using an in vitro selection scheme, we
      identified two base-pairs in the I-TevI cleavage site region as important for
      cleavage efficiency. These were confirmed by comparison of I-TevI cleavage
      efficiencies on mutant and on wild-type substrates. We also showed that nicking
      of the bottom strand by I-TevI is not affected by mutation of residues
      surrounding the bottom-strand cleavage site, unlike other homing endonucleases.
      One of these two base-pairs is universally conserved in all TS sequences, and is
      identical with a previously identified cleavage determinant of I-BmoI, a related
      GIY-YIG endonuclease that binds a homologous stretch of TS-encoding DNA. The
      other base-pair is conserved only in a subset of TS genes that includes the I
      TevI, but not the I-BmoI, target sequence. Both the I-TevI and I-BmoI cleavage
      site requirements correspond to functionally critical residues involved in an
      extensive hydrogen bond network within the TS active site. Remarkably, these
      cleavage requirements correlate with TS phylogeny in bacteria, suggesting that
      each endonuclease has individually adapted to efficiently cleave distinct TS
      substrates.

PMID- 15491610
TI  - Crystallization of transmembrane proteins in cubo: mechanisms of crystal growth
      and defect formation.
AB  - Crystallization of membrane proteins is a major stumbling block en route to
      elucidating their structure and understanding their function. The novel concept
      of membrane protein crystallization from lipidic cubic phases, "in cubo", has
      yielded well-ordered crystals and high-resolution structures of several membrane
      proteins, yet progress has been slow due to the lack of understanding of the
      molecular mechanisms of protein transport, crystal nucleation, growth, and defect
      formation in cubo. Here, we examine at molecular and mesoscopic resolution with
      atomic force microscopy the morphology of in cubo grown bacteriorhodopsin
      crystals in inert buffers and during etching by detergent. The results reveal
      that crystal nucleation occurs following local rearrangement of the highly curved
      lipidic cubic phase into a lamellar structure, which is akin to that of the
      native membrane. Crystals grow within the bulk cubic phase surrounded by such
      lamellar structures, whereby transport towards a growing crystalline layer is
      constrained to within an individual lamella. This mechanism leads to lack of
      dislocations, generation of new crystalline layers at numerous locations, and to
      voids and block boundaries. The characteristic macroscopic lengthscale of these
      defects suggests that the crystals grow by attachment of single molecules to the
      nuclei. These insights into the mechanisms of nucleation, growth and transport in
      cubo provide guidance en route to a rational design of membrane protein
      crystallization, and promise to further advance the field.

PMID- 15491611
TI  - Conserved residues in the HIV-1 Nef hydrophobic pocket are essential for
      recruitment and activation of the Hck tyrosine kinase.
AB  - The Nef protein of the primate lentiviruses human immunodeficiency virus (HIV)
      and simian immunodeficiency virus (SIV) is essential for high-titer viral
      replication and acquired immune deficiency syndrome (AIDS) progression. Nef binds
      to the macrophage-specific Src family member Hck through its SH3 domain,
      resulting in constitutive kinase activation capable of transforming rodent
      fibroblasts. Nef-Hck interaction may be essential for M-tropic HIV replication
      and AIDS pathogenesis, identifying this virus-host protein complex as a rational
      target for anti-HIV drug discovery. Here, we investigated whether interaction
      with Hck is a common feature of Nef alleles from different strains of HIV-1. We
      compared the ability of four different laboratory HIV-1 Nef alleles (SF2, LAI,
      ELI, and Consensus) to induce Hck activation and transformation in our Rat-2
      fibroblast model. While SF2, LAI, and Consensus Nef all bound and activated Hck,
      ELI Nef failed to bind to the Hck SH3 domain in vitro and did not cooperate with
      Hck in fibroblast transformation. Molecular modeling identified three residues in
      the core region of SF2 Nef (Ala83, His116, and Tyr120) which are substituted in
      ELI with Glu, Asn, and Ile, respectively. Two of these residues (Ala83 and
      Tyr120) form part of the hydrophobic pocket that contacts Ile 96 in the RT loop
      of the Hck SH3 domain in the Nef-SH3 crystal structure. Substitution of SF2 Nef
      Tyr120 with Ile completely abolished Hck recruitment and activation. In a
      complementary experiment, substitution of ELI Ile120 with Tyr partly restored ELI
      Nef-induced Hck activation and transformation in Rat-2 cells. Hck activation
      increased further by substitution of ELI Glu83 with Ala and Asn116 with His,
      suggestive of a supportive role for these residues in Hck binding. This study
      provides the first biological evidence that the HIV-1 Nef hydrophobic pocket is
      critical to Hck recruitment and activation in vivo. Targeting the Nef hydrophobic
      pocket with a small molecule may be sufficient to disrupt Nef signaling through
      Hck in HIV-infected macrophages, slowing disease progression.

PMID- 15491612
TI  - The origin of enantioselectivity in aldolase antibodies: crystal structure, site
      directed mutagenesis, and computational analysis.
AB  - Catalytic aldolase antibodies, generated by reactive immunization, catalyze the
      aldol reaction with the efficiency of natural enzymes, but accept a much broader
      range of substrates. Two separate groups of aldolase antibodies that catalyze the
      same aldol reactions with antipodal selectivity were analyzed by comparing their
      amino acid sequences with their crystal structures, site-directed mutagenesis
      data, and computational docking of the transition states of the aldol reaction.
      The crystal structure of aldolase antibody 93F3 Fab' at 2.5A resolution revealed
      a combining site with two lysine residues, including LysL89 that reacts to form
      the covalent enamine intermediate. In contrast, antibody 33F12 has one active
      site lysine, LysH93. The reactive lysine residues in each group of antibodies are
      differentially located on the heavy and light chain variable regions in pseudo
      symmetric opposite orientations, but both within highly hydrophobic environments.
      Thus, the defining feature for the observed enantioselectivities of these
      aldolase antibody catalysts is the respective location and relative disposition
      of the reactive lysine residues within the active sites of these catalysts.

PMID- 15491613
TI  - Crystal structures of beta-galactosidase from Penicillium sp. and its complex
      with galactose.
AB  - Beta-galactosidases catalyze the hydrolysis of beta(1-3) and beta(1-4) galactosyl
      bonds in oligosaccharides as well as the inverse reaction of enzymatic
      condensation and transglycosylation. Here we report the crystallographic
      structures of Penicillium sp. beta-galactosidase and its complex with galactose
      solved by the SIRAS quick cryo-soaking technique at 1.90 A and 2.10 A resolution,
      respectively. The amino acid sequence of this 120 kDa protein was first assigned
      putatively on the basis of inspection of the experimental electron density maps
      and then determined by nucleotide sequence analysis. Primary structure alignments
      reveal that Penicillium sp. beta-galactosidase belongs to family 35 of glycosyl
      hydrolases (GHF-35). This model is the first 3D structure for a member of GHF-35.
      Five distinct domains which comprise the structure are assembled in a way
      previously unobserved for beta-galactosidases. Superposition of this complex with
      other beta-galactosidase complexes from several hydrolase families allowed the
      identification of residue Glu200 as the proton donor and residue Glu299 as the
      nucleophile involved in catalysis. Penicillium sp. beta-galactosidase is a
      glycoprotein containing seven N-linked oligosaccharide chains and is the only
      structure of a glycosylated beta-galactosidase described to date.

PMID- 15491614
TI  - Double belt structure of discoidal high density lipoproteins: molecular basis for
      size heterogeneity.
AB  - We recently proposed an all-atom model for apolipoprotein (apo) A-I in discoidal
      high-density lipoprotein in which two monomers form stacked antiparallel helical
      rings rotationally aligned by interhelical salt-bridges. The model can be derived
      a priori from the geometry of a planar bilayer disc that constrains the
      hydrophobic face of a continuous amphipathic alpha helix in lipid-associated apoA
      I to a plane inside of an alpha-helical torus. This constrains each apoA-I
      monomer to a novel conformation, that of a slightly unwound, curved, planar
      amphipathic alpha 11/3 helix (three turns per 11 residues). Using non-denaturing
      gradient gel electrophoresis, we show that dimyristoylphosphocholine discs
      containing two apoA-I form five distinct particles with maximal Stokes diameters
      of 98 A (R2-1), 106 A (R2-2), 110 A (R2-3), 114 A (R2-4) and 120 A (R2-5).
      Further, we show that the Stokes diameters of R2-1 and R2-2 are independent of
      the N-terminal 43 residues (the flexible domain) of apoA-I, while the flexible
      domain is necessary and sufficient for the formation of the three larger
      complexes. On the basis of these results, the conformation of apoA-I on the R2-2
      disc can be modeled accurately as an amphipathic helical double belt extending
      the full length of the lipid-associating domain with N and C-terminal ends in
      direct contact. The smallest of the discs, R2-1, models as the R2-2 conformation
      with an antiparallel 15-18 residue pairwise segment of helixes hinged off the
      disc edge. The conformations of full-length apoA-I on the flexible domain
      dependent discs (R2-3, R2-4 and R2-5) model as the R2-2 conformation extended on
      the disc edge by one, two or three of the 11-residue tandem amphipathic helical
      repeats (termed G1, G2 and G3), respectively, contained within the flexible
      domain. Although we consider these results to favor the double belt model, the
      topographically very similar hairpin-belt model cannot be ruled out entirely.

PMID- 15491615
TI  - Crystal structures of calpain-E64 and -leupeptin inhibitor complexes reveal
      mobile loops gating the active site.
AB  - The endogenous calpain inhibitor, calpastatin, modulates some patho-physiological
      aspects of calpain signaling. Excess calpain can escape this inhibition and as
      well, many calpain isoforms and autolytically generated protease core fragments
      are not inhibited by calpastatin. There is a need, therefore, to develop
      specific, cell-permeable calpain inhibitors to block uncontrolled proteolysis and
      prevent tissue damage during brain and heart ischemia, spinal-cord injury and
      Alzheimer's diseases. Here, we report the first high-resolution crystal
      structures of rat mu-calpain protease core complexed with two traditional, low
      molecular mass inhibitors, leupeptin and E64. These structures show that access
      to a slightly deeper, but otherwise papain-like active site is gated by two
      flexible loops. These loops are divergent among the calpain isoforms giving a
      potential structural basis for substrate/inhibitor selectivity over other papain
      like cysteine proteases and between members of the calpain family.

PMID- 15491616
TI  - The dimeric and trimeric solution structures of the multidomain complement
      protein properdin by X-ray scattering, analytical ultracentrifugation and
      constrained modelling.
AB  - Properdin regulates the alternative pathway of the complement system of immune
      defence by stabilising the C3 convertase complex. It contains six thrombospondin
      repeat type I (TSR-1 to TSR-6) domains and an N-terminal domain. Properdin exists
      as either a dimer, trimer or tetramer. In order to determine the solution
      structure of multiple TSR domains, the molecular structures of dimeric and
      trimeric properdin were studied by X-ray scattering and analytical
      ultracentrifugation. Guinier analyses showed that the dimer and trimer have radii
      of gyration R(G) values of 7.5 nm and 10.3 nm, respectively, and cross-sectional
      radii of gyration R(XS) values of 1.3 nm and 1.5 nm, respectively. Distance
      distribution functions showed that the maximum lengths of the dimer and trimer
      were 25 nm and 30 nm, respectively. Analytical ultracentrifugation gave
      sedimentation coefficients of 5.1S and 5.2S for the dimer and trimer forms,
      respectively. Homology models for the TSR domains were constructed using the
      crystal structure of the TSP-2 and TSP-3 domains in human thrombospondin as
      templates. Properdin could be represented by seven TSR domains, not six as
      believed, since the crystal structure determined for TSP-2 and TSP-3 showed that
      the N-terminal domain (TSR-0) could be represented by a truncated TSR domain with
      the same six conserved Cys residues found in TSR-1 to TSR-6. Automated
      constrained molecular modelling revealed the solution conformations of multiple
      TSR domains in properdin at medium resolution. The comparison of 3125
      systematically generated conformational models for the trimer with the X-ray data
      showed that good curve fits could be obtained by assuming that the linker between
      adjacent TSR domains possessed limited flexibility. Good trimer models correspond
      to partially collapsed triangular structures, and extended triangular shapes do
      not fit the data. The corresponding 3125 models for the dimer revealed a similar
      outcome in which a partially collapsed TSR structure gave good fits. The models
      account for the effect of mutations that cause properdin deficiencies, and
      suggest that the biologically active TSR-4, TSR-5 and TSR-6 domains are exposed
      for protein-protein interactions. The role of the other TSR domains in properdin
      may be to act as spacers to make TSR-4, TSR-5 and TSR-6 accessible for function.

PMID- 15491617
TI  - New X-ray diffraction observations on vertebrate muscle: organisation of C
      protein (MyBP-C) and troponin and evidence for unknown structures in the
      vertebrate A-band.
AB  - Previous low-angle X-ray diffraction studies of various vertebrate skeletal
      muscles have shown the presence of two rich layer-line patterns, one from the
      myosin heads and based on a 429 A axial repeat, and one from actin filaments and
      based on a repeat of about 360-370 A. In addition, meridional intensities have
      been seen from C-protein (MyBP-C; at about 440 A and its higher orders) and
      troponin (at about 385 A and its orders). Using preparations of intact, relaxed,
      bony fish fin muscles and the ID-02 low-angle X-ray camera at the ESRF with a 10
      m camera length we have now seen numerous, hitherto unreported, sampled, X-ray
      layer-lines many of which do not fit onto the previously observed repeats and
      which require interpretation. The new reflections all fall on the normal
      ("vertical") hexagonal lattice row-lines in the highly sampled, almost
      "crystalline", low-angle diffraction X-ray patterns from bony fish muscle,
      indicating that they all arise from the muscle A-band. However, they do not fall
      on a single axial repeat. In direct confirmation of our previous analysis, some
      of these new reflections are explained by the interaction in resting muscle
      between the N-terminal ends of myosin-bound C-protein molecules with adjacent
      actin filaments, possibly through the Pro-Ala-rich region. Other newly observed
      reflections lie on a much longer repeat, but they are most easily interpreted in
      terms of the arrangement of troponin on the actin filaments. If this is so, then
      the implication is that the actin filaments and their troponin complexes are
      systematically arranged in the fish muscle A-band lattice relative to the myosin
      head positions, and that these newly observed X-ray reflections, when fully
      analysed, will report on the shape and distribution of troponin molecules in the
      resting muscle A-band. The less certain contributions of titin and nebulin to
      these new reflections have also been tested and are described. Many of the new
      reflections do not appear to come from these known structures. There must be
      structural features of the A-band that have not yet been described.

PMID- 15491618
TI  - Solution structure and heparin interaction of human hepatoma-derived growth
      factor.
AB  - Hepatoma-derived growth factor (HDGF)-related proteins (HRPs) comprise a new
      protein family that has been implicated in nephrogenesis, tumorigenesis, vascular
      development, cell proliferation, and transcriptional activation. All HRPs share a
      conserved N-terminal homologous to the amino terminus of HDGF (HATH) domain, but
      vary significantly in the C-terminal region. Here, we show that in solution the N
      and C termini of human HDGF form two structurally independent domains. The 100
      amino acid residue N-terminal HATH domain is well-structured while the 140 amino
      acid residue C-terminal domain is disordered. We determined the solution
      structure of the HATH domain by NMR. The core structure of the HATH domain is a
      five-stranded beta-barrel followed by two alpha-helices, similar to those of PWWP
      domains of known structures. Surface plasmon resonance results showed that the
      HATH domain is primarily responsible for heparin binding. On the basis of the
      chemical shift perturbation induced by binding of heparin-derived hexasaccharide,
      we identified a prominent, highly positively charged region as the putative
      heparin-binding site. Sequence comparison and structure prediction suggest that
      all HRPs are likely to adapt a similar modular structure.

PMID- 15491619
TI  - Rapid analysis of large protein-protein complexes using NMR-derived orientational
      constraints: the 95 kDa complex of LpxA with acyl carrier protein.
AB  - Characterization of protein-protein interactions that are critical to the
      specific function of many biological systems has become a primary goal of
      structural biology research. Analysis of these interactions by structural
      techniques is, however, challenging due to inherent limitations of the techniques
      and because many of the interactions are transient, and suitable complexes are
      difficult to isolate. In particular, structural studies of large protein
      complexes by traditional solution NMR methods are difficult due to a priori
      requirement of extensive assignments and a large number of intermolecular
      restraints for the complex. An approach overcoming some of these challenges by
      utilizing orientational restraints from residual dipolar couplings collected on
      solution NMR samples is presented. The approach exploits existing structures of
      individual components, including the symmetry properties of some of these
      structures, to assemble rapidly models for relatively large protein-protein
      complexes. An application is illustrated with a 95 kDa homotrimeric complex of
      the acyltransferase protein, LpxA (UDP-N-acetylglucosamine acyltransferase), and
      acyl carrier protein. LpxA catalyzes the first step in the biosynthesis of the
      lipid A component of lipopolysaccharide in Gram-negative bacteria. The structural
      model generated for this complex can be useful in the design of new anti
      bacterial agents that inhibit the biosynthesis of lipid A.

PMID- 15491620
TI  - NMR characterization of full-length farnesylated and non-farnesylated H-Ras and
      its implications for Raf activation.
AB  - The C terminus, also known as the hypervariable region (residues 166-189), of H-,
      N-, and K-Ras proteins has sequence determinants necessary for full activation of
      downstream effectors such as Raf kinase and PI-3 kinase as well as for the
      correct targeting of Ras proteins to lipid rafts and non-raft membranes. There is
      considerable interest in understanding how residues in the extreme C terminus of
      the different Ras proteins and farnesylation of the CaaX box cysteine affect Ras
      membrane localization and allosteric activation of Raf kinase. To provide
      insights into the structural and dynamic changes that occur in Ras upon
      farnesylation, we have used NMR spectroscopy to compare the properties of
      truncated H-Ras (1-166), to non-processed full-length H-Ras (residues 1-185) and
      full-length (1-189) farnesylated H-Ras. We report that the C-terminal helix alpha
      5 extends to residue N172, and the remaining 17 amino acid residues in the C
      terminus are conformationally averaged in solution. Removal of either 23 or 18
      amino acid residues from the C terminus of full length H-Ras generates truncated
      H-Ras (1-166) and H-Ras (1-171) proteins, respectively, that have been
      structurally characterized and are biochemical active. Here we report that C
      terminal truncation of H-Ras results in minor structural and dynamic
      perturbations that are propagated throughout the H-Ras protein including
      increased flexibility of the central beta-sheet and the C-terminal helix alpha-5.
      Ordering of residues in loop-2, which is involved in Raf CRD binding is also
      observed. Farnesylation of full-length H-Ras at C186 does not result in
      detectable conformational changes in H-Ras. Chemical shift mapping studies of
      farnesylated and non-farnesylated forms of H-Ras with the Raf-CRD show that the
      farnesyl moiety, the extreme H-Ras C terminus and residues 23-30, contribute to H
      Ras:Raf-CRD interactions, thereby increasing the affinity of H-Ras for the Raf
      CRD.

PMID- 15491621
TI  - Structure of bovine rhodopsin in a trigonal crystal form.
AB  - We have determined the structure of bovine rhodopsin at 2.65 A resolution using
      untwinned native crystals in the space group P3(1), by molecular replacement from
      the 2.8 A model (1F88) solved in space group P4(1). The new structure reveals
      mechanistically important details unresolved previously, which are considered in
      the membrane context by docking the structure into a cryo-electron microscopy map
      of 2D crystals. Kinks in the transmembrane helices facilitate inter-helical polar
      interactions. Ordered water molecules extend the hydrogen bonding networks,
      linking Trp265 in the retinal binding pocket to the NPxxY motif near the
      cytoplasmic boundary, and the Glu113 counterion for the protonated Schiff base to
      the extracellular surface. Glu113 forms a complex with a water molecule hydrogen
      bonded between its main chain and side-chain oxygen atoms. This can be expected
      to stabilise the salt-bridge with the protonated Schiff base linking the 11-cis
      retinal to Lys296. The cytoplasmic ends of helices H5 and H6 have been extended
      by one turn. The G-protein interaction sites mapped to the cytoplasmic ends of H5
      and H6 and a spiral extension of H5 are elevated above the bilayer. There is a
      surface cavity next to the conserved Glu134-Arg135 ion pair. The cytoplasmic
      loops have the highest temperature factors in the structure, indicative of their
      flexibility when not interacting with G protein or regulatory proteins. An
      ordered detergent molecule is seen wrapped around the kink in H6, stabilising the
      structure around the potential hinge in H6. These findings provide further
      explanation for the stability of the dark state structure. They support a
      mechanism for the activation, initiated by photo-isomerisation of the chromophore
      to its all-trans form, that involves pivoting movements of kinked helices, which,
      while maintaining hydrophobic contacts in the membrane interior, can be coupled
      to amplified translation of the helix ends near the membrane surfaces.

PMID- 15491622
TI  - Crystals of native and modified bovine rhodopsins and their heavy atom
      derivatives.
AB  - Rhodopsin, the pigment protein responsible for dim-light vision, is a G protein
      coupled receptor that converts light absorption into the activation of a G
      protein, transducin, to initiate the visual response. We have crystallised
      detergent-solubilised bovine rhodopsin in the native form and after chemical
      modifications as needles 10-40 microm in cross-section. The crystals belong to
      the trigonal space group P3(1), with two molecules of rhodopsin per asymmetric
      unit, related by a non-crystallographic 2-fold axis parallel with the
      crystallographic screw axis along c (needle axis). The unit cell dimensions are
      a=103.8 A, c=76.6 A for native rhodopsin, but vary over a wide range after heavy
      atom derivatisation, with a between 101.5 A and 113.9 A, and c between 76.6 A and
      79.2 A. Rhodopsin molecules are packed with the bundle of transmembrane helices
      tilted from the c-axis by about 100 degrees . The two molecules in the asymmetric
      unit form contacts along the entire length of their transmembrane helices 5 in an
      antiparallel orientation, and they are stacked along the needle axis according to
      the 3-fold screw symmetry. Hence hydrophobic contacts are prominent at protein
      interfaces both along and normal to the needle axis. The best crystals of native
      rhodopsin in this crystal form diffracted X-rays from a microfocused synchrotron
      source to 2.55 A maximum resolution. We describe steps taken to extend the
      diffraction limit from about 10 A to 2.6 A.

PMID- 15491623
TI  - Genomic determinants of protein folding thermodynamics in prokaryotic organisms.
AB  - Here we investigate how thermodynamic properties of orthologous proteins are
      influenced by the genomic environment in which they evolve. We performed a
      comparative computational study of 21 protein families in 73 prokaryotic species
      and obtained the following main results. (i) Protein stability with respect to
      the unfolded state and with respect to misfolding are anticorrelated. There
      appears to be a trade-off between these two properties, which cannot be optimized
      simultaneously. (ii) Folding thermodynamic parameters are strongly correlated
      with two genomic features, genome size and G+C composition. In particular, the
      normalized energy gap, an indicator of folding efficiency in statistical
      mechanical models of protein folding, is smaller in proteins of organisms with a
      small genome size and a compositional bias towards A+T. Such genomic features are
      characteristic for bacteria with an intracellular lifestyle. We interpret these
      correlations in light of mutation pressure and natural selection. A mutational
      bias toward A+T at the DNA level translates into a mutational bias toward more
      hydrophobic (and in general more interactive) proteins, a consequence of the
      structure of the genetic code. Increased hydrophobicity renders proteins more
      stable against unfolding but less stable against misfolding. Proteins with high
      hydrophobicity and low stability against misfolding occur in organisms with
      reduced genomes, like obligate intracellular bacteria. We argue that they are
      fixed because these organisms experience weaker purifying selection due to their
      small effective population sizes. This interpretation is supported by the
      observation of a high expression level of chaperones in these bacteria. Our
      results indicate that the mutational spectrum of a genome and the strength of
      selection significantly influence protein folding thermodynamics.

PMID- 15491624
TI  - Probing the high energy states in proteins by proteolysis.
AB  - Unless the native conformation has an unstructured region, proteases cannot
      effectively digest a protein under native conditions. Digestion must occur from a
      higher energy form, when at least some part of the protein is exposed to solvent
      and becomes accessible by proteases. Monitoring the kinetics and denaturant
      dependence of proteolysis under native conditions yields insight into the
      mechanism of proteolysis as well as these high-energy conformations. We propose
      here a generalized approach to exploit proteolysis as a tool to probe high-energy
      states in proteins. This "native state proteolysis" experiment was carried out on
      Escherichia coli ribonuclease HI. Mass spectrometry and N-terminal sequencing
      showed that thermolysin cleaves the peptide bond between Thr92 and Ala93 in an
      extended loop region of the protein. By comparing the proteolysis rate of the
      folded protein and a peptidic substrate mimicking the sequence at the cleavage
      site, the energy required to reach the susceptible state (Delta G(proteolysis))
      was determined. From the denaturant dependence of Delta G(proteolysis), we
      determined that thermolysin digests this protein through a local fluctuation,
      i.e. localized unfolding with minimal change in solvent assessable surface area.
      Proteolytic susceptibilities of proteins are discussed based on the finding of
      this local fluctuation mechanism for proteolysis under native conditions.

PMID- 15491625
TI  - Detection and structure determination of an equilibrium unfolding intermediate of
      Rd-apocytochrome b562: native fold with non-native hydrophobic interactions.
AB  - The absence of detectable kinetic and equilibrium folding intermediates by
      optical probes is commonly taken to indicate that protein folding is a two-state
      process. However, for some small proteins with apparent two-state behavior,
      unfolding intermediates have been identified in native-state hydrogen exchange or
      kinetic unfolding experiments monitored by nuclear magnetic resonance. Rd
      apocytochrome b(562), a four-helix bundle, is one such protein. Here, we found
      another unfolding intermediate for Rd-apocytochrome b(562). It is based on a
      cooperative transition of (15)N chemical shifts of amide protons as a function of
      urea concentrations before the global unfolding. We have solved the high
      resolution structure of the protein at 2.8 M urea, which is after this
      cooperative transition but before the global unfolding. All four helices remained
      intact, but a number of hydrophobic core residues repacked. This intermediate
      provides a possible structural interpretation for the kinetic unfolding
      intermediates observed using nuclear magnetic resonance methods for several
      proteins and has important implications for theoretical studies of protein
      folding.

PMID- 15491626
TI  - Complex interactions at the helix-helix interface stabilize the glycophorin A
      transmembrane dimer.
AB  - To explore the residue interactions in the glycophorin A dimerization motif, an
      alanine scan double mutant analysis at the helix-helix interface was carried out.
      These data reveal a combination of additive and coupled effects. The majority of
      the double mutants are found to be equally or slightly more stable than would be
      predicted by the sum of the energetic cost of the single-point mutants. The
      proximity of the mutated sites is not related to the presence of coupling between
      those sites. Previous studies reveal that a single face of the glycophorin A
      monomer contains a specific glycine-containing motif (GxxxG) that is thought to
      be a driving force for the association of transmembrane helices. Double mutant
      cycles suggest that the relationship of the GxxxG motif to the remainder of the
      helix-helix interface is complex. Sequences containing mutations that abolish the
      GxxxG motif retain an ability to dimerize, while a sequence containing a GxxxG
      motif appears unable to form dimers. The energetic effects of weakly coupled and
      additive double mutants can be explained by changes in van der Waals interactions
      at the dimer interface. These results emphasize the fact that the sequence
      context of the dimer interface modulates the strength of the glycophorin A GxxxG
      mediated transmembrane dimerization reaction.

PMID- 15491627
TI  - N-methyl-N'-nitro-N-nitrosoguanidine sensitivity, mutator phenotype and sequence
      specificity of spontaneous mutagenesis in FEN-1-deficient cells.
AB  - Intact pZ189 DNA was allowed to replicate in FL-FEN-1(-) cell line that was
      established in this laboratory in which the expression of FEN-1 gene was blocked
      by dexamethasone-inducible expression of antisense RNA to FEN-1. E. coli MBM7070
      was transfected with the replicated plasmid, and those with mutations in the supF
      gene were identified. The frequency of mutants that did not contain recognizable
      changes in the electrophoretic mobility of the plasmid DNA was scored. The
      frequency of such mutants was 19.1 x 10(-4) (34/17781), significantly higher than
      those of 2.9 x 10(-4) (4/13668) and 3.0 x 10(-4) (3/9857) in the corresponding
      controls, respectively. Sequence analysis of the supF genes of these mutants
      showed that all (37/37) the base substitutions occurred at C:G base pairs; 68%
      (23/37) of the base substitutions were base transversions, while 32% (12/37) were
      transitions. Approximately 76% (23/37) of these base substitutions occurred
      frequently at nine positions; two of these sites contain triple pyrimidine (T or
      C) repeat upstream to the mutated base; four of these sites consist of 5'-TTN1N2
      and mutations occurred at N1 site sequence; another two sites have the
      characteristics of triple A flanked at both 5' and 3' side by TCT, with the base
      substitution occurring at C in the context sequence. These data suggested that
      these sites are the hot spot of mutagenesis in plasmid replicated in FEN-1
      deficient cells. Besides the mutator phenotype of the FEN-1-deficient cell, it
      was also demonstrated that FEN-1-deficient cell exhibited an increased N-methyl
      N'-nitro-N-nitrosoguanidine (MNNG) sensitive phenotype.

PMID- 15491628
TI  - Mutation spectrum in sunlight-exposed mouse skin epidermis: small but appreciable
      contribution of oxidative stress-mediated mutagenesis.
AB  - We studied the mutations induced in skin by sunlight using transgenic Muta mice.
      Noon sunlight during summer at Sendai, Japan induced mutations efficiently in
      both epidermis and dermis. The mutant frequency (MF) in epidermis reached nearly
      0.5% during the first 40 min irradiation but became saturated at this level with
      the appearance of skin inflammation after further irradiation. At the equivalent
      inflammatory dose, sunlight was twice as genotoxic as 313 nm-peak UVB. The 81
      mutations detected in 80 lacZ transgene mutants isolated from the sunlight
      exposed epidermis were dominated by C --> T transitions (89%), occurring
      exclusively at dipyrimidine sites, and also included a CC --> TT tandem
      substitution. Thus, the sunlight-induced mutation spectrum is highly UV-specific,
      quite similar to that induced by UVB but significantly different from that
      induced by UVA. Although oxidative damage-related C --> A transversions were
      detected only in five mutants (6%), their frequency was elevated to at least 15
      times the background level, suggesting that the contribution of UVA-mediated
      oxidative stress is comparatively small but considerable. An analysis of bases
      adjacent to the mutated cytosines revealed that the sunlight-induced mutations
      prefer 5'-TC-3' dipyrimidine sites to 5'-CC-3' and 5'-CT-3'. The distribution of
      the frequent C --> T transition sites in the transgene was well associated with
      the CpG motif, which is known to be completely methylated in the gene, and quite
      similar to that induced by UVB rather than that by UVA. Thus, the UVB component
      contributes to the sunlight-induced mutations in the mammalian skin much more
      than the UVA component, whose influence through reactive oxygen species (ROS)
      mediated mutagenesis is still appreciable.

PMID- 15491629
TI  - Sensitivity and variability of visual scoring in the comet assay. Results of an
      inter-laboratory scoring exercise with the use of silver staining.
AB  - Nineteen scorers from seven Cuban laboratories participated in this slide
      exercise designed to test the influence of the scorer on the accuracy,
      sensitivity and variability of the comet assay when a visual method of DNA damage
      evaluation is used. The assay was performed using human lymphocytes from a single
      donor exposed in vitro for 5 min at 0 degrees C to doses of 0, 5, 10, 25, 50, 100
      and 200 microM of hydrogen peroxide. Each participant scored the same set of 14
      coded slides with silver stained comets. The comets were classified visually into
      five categories according to the appearance resulting from the relative
      proportion of DNA in the tail. The extent of DNA damage was expressed in
      arbitrary units. At zero dose the median values of 12 scorers out of 19 were
      included between the values of the overall 25 and 75 per thousand. This
      proportion remains practically the same as the dose increases. The lowest dose
      detected by this method for the majority of scorers (11) was 10 microM. The
      coefficient of variation at the control dose was the highest (median value 26%),
      progressively declined to 20%, and starting from 25 microM, values are around
      10%. The results of the exercise show the reliability of the silver staining and
      visual scoring for the comet method.

PMID- 15491630
TI  - Induced of plastid mutations in soybean plant (Glycine max L. Merrill) with gamma
      radiation and determination with RAPD.
AB  - The aim of our study was to induce with radiation of atrazine resistant and
      tolerated mutants in Coles, Amsoy-71 and 1937 soybean varieties. Atrazine that is
      photosynthetic inhibitor is the most important herbicide of S-triazin group, and
      shows toxic effect on soybean plant. For the improvement of the atrazine
      resistant plants with mutation breeding, the seeds belonging to the three
      varieties were irradiated with 200 Gy of gamma radiation dose. The irradiated
      seeds were sown in the field and at the end of harvesting season, every pod at
      node situated on the main stem was picked up separately and M2 generations were
      obtained. At the plants, which were obtained from M2 generation, chlorophyll
      mutants were determined and atrazine selection was made. The percentage of
      chlorophyll mutants for Amsoy-71, Coles and 1937 soybean varieties were found as
      1.07, 1.48 and 1.32, respectively. At the end of atrazine selection, the
      percentages of atrazine resistant plants for Amsoy-71, Coles and 1937 soybean
      varieties were 0.80, 0.60 and 0.53, respectively. The percentages of atrazine
      tolerated plants were 1.07, 1.18 and 1.05, respectively as well. In our research;
      the differences among the mutants replying to atrazine in various concentrations
      were examined by using RAPD procedure as the molecular marker techniques in
      comparison with polymorphism. In the study done by using 14 primers; according to
      the amplification results, the differences between atrazine resistant plants were
      shown.

PMID- 15491631
TI  - Impact of mismatch repair deficiency on genomic stability in the maternal
      germline and during early embryonic development.
AB  - The effects of lack of the mismatch repair protein PMS2 on germline and maternal
      effect mutations were studied in transgenic mice that allow mutant cells to be
      visualized in situ. Tg(betaA-G11PLAP) mice are transgenic for the G11 allele of a
      human placental alkaline phosphatase (PLAP) gene driven by a human beta-actin
      promoter. The G11 allele of the PLAP gene does not produce enzyme due to a
      frameshift induced by a mononucleotide repeat containing 11 G:C basepairs. Loss
      of one G:C basepair restores enzyme production. When the G11 PLAP allele was
      passed through the germline of female mice lacking PMS2, approximately 25% of the
      offspring that inherited the transgene exhibited the phenotype expected for
      germline mutation. The mice transmitted the germline-mutation phenotype normally
      and their offspring exhibited PLAP enzyme activity in at least 30% of the cells
      in each tissue examined. By contrast, only 1 of 32 mice that inherited the G11
      PLAP transgene from a wild-type male crossed to a Pms2-/- female exhibited a high
      number of PLAP+ cells. Compared to germline revertants, approximately one half to
      one quarter as many cells were PLAP+, suggesting that a mutation occurred in one
      cell of an embryo containing two to four cells. These data suggest that the
      paternally derived Pms2 gene provided normal levels of PMS2 protein to embryos by
      the time they reached the eight-cell stage, but that smaller embryos formed from
      PMS2-deficient eggs lacked PMS2 function.

PMID- 15491632
TI  - Comparison of p53 levels in lymphocytes and in blood plasma of nuclear power
      plant workers.
AB  - p53 levels were assessed in lymphocytes and in blood plasma of workers from two
      Czech nuclear power plants (NPP): 114 subjects working in Temelin and 108
      subjects working in Dukovany. Ionizing radiation (IR) exposure data were
      available for 64 and 59 subjects working in the monitored zones from the NPP in
      Temelin and Dukovany, respectively. The short-term doses of IR for these subjects
      were 0.01 and 0.12 mSv, and the long-term doses were 0.46 and 5.68 mSv, in the
      Temelin and Dukovany NPP, respectively. As a control group, 46 subjects living in
      Ceske Budejovice, a city nearby the Temelin NPP, were analyzed. The concentration
      of p53 in lymphocytes was significantly higher in workers from the monitored zone
      in the Dukovany NPP (median value 6.4 pg/microg protein, P <0.001) than in
      workers from the Temelin NPP (3.2 pg/microg) as well as in the control group (3.5
      pg/microg). In contrast, plasma levels of p53 were comparable in the control
      group (median value 116 pg/ml plasma) and workers from the monitored zone of
      Dukovany NPP (102 pg/ml), but lower in workers from Temelin NPP (5 pg/ml). Other
      factors affecting p53 levels were studied. Smoking resulted in increased p53
      lymphocyte levels. The effect of polymorphisms in metabolic and DNA repair genes
      on p53 levels was analyzed. The correlation was found between p53 levels in
      lymphocytes and p53 codon 72 polymorphism in subjects working in NPPs, but not in
      the control group. The results of measurement p53 levels in lymphocytes suggest
      that this biomarker could reflect the short-term as well as long-term effects of
      low doses IR. Its impact on human health should be further explored.

PMID- 15491633
TI  - Delineation of antimutagenic activity of catechin, epicatechin and green tea
      extract.
AB  - Tea is consumed worldwide as second largest to water in popularity as a beverage.
      It has been reported that tea extracts have antibacterial, antiviral,
      antioxidative, antitumor and antimutagenic activities. The protective effect of
      green tea has been assumed to be due to the powerful scavenging and antioxidative
      property of high concentrations of unpolymerised catechins and their gallates. In
      the present proposal green tea extract (GT), (+)-catechin (C) and (-)-epicatechin
      (EC) were investigated for their antioxidant activity by different in vitro
      methods like (i) DPPH assay (ii) superoxide anion scavenging and (iii) hydrogen
      peroxide scavenging activity. Further these agents were also tested against
      mutagenesis using the well-standardized Ames microsomal test system. The Ames
      tester strain Salmonella typhimurium TA102, which readily responds to reactive
      oxygen species, was used and the antimutagenic activity was evaluated against
      oxidative mutagens tertiary butyl hydroperoxide (ID50-24.41, 29.63 and 113.23
      microg for EC, C and GT, respectively) and hydrogen peroxide (ID50-17.3, 18.4 and
      88.1 microg for EC, C and GT, respectively). Ascorbic acid was used as a standard
      antioxidant in all the experiments. Results indicate that all the three agents
      possess excellent DPPH free radical scavenging activity (IC50-1.5 microg for EC,
      3.45 microg for C and 3.8 microg for GT), good hydrogen peroxide (IC50-11.18
      microg for EC, 13.5 microg for C and 11.78 microg for GT) and superoxide anion
      scavenging (IC50-1.64 microg for EC, 1.74 microg for C and 3.52 microg for GT)
      activities. Further, they also show antimutagenic activity in the above-mentioned
      test systems establishing their antioxidant nature to be responsible for such
      activity. The in vitro antioxidant activity correlates well with the
      antimutagenic action. (-)-Epicatechin is indicated to be a better agent in
      comparison to the other two agents (ID50-1.2 times more than C and 5 times more
      than GT in antimutagenicity studies against t-BOOH and hydrogen peroxide induced
      mutagenesis). Ascorbic acid however showed a much less activity (ID50-12.1 mg
      against t-BOOH and 7.2 mg with hydrogen peroxide induced mutagenesis).

PMID- 15491634
TI  - Effects of tannic acid and its related compounds on food mutagens or hydrogen
      peroxide-induced DNA strands breaks in human lymphocytes.
AB  - The effect of tannic acid (TA), gallic acid (GA), propyl gallate (PA) and ellagic
      acid (EA) on DNA damage in human lymphocytes induced by food mutagens [3-amino-1
      methyl-5H-pyrido (4,3-b) indole (Trp-P-2) and 2-amino-1-methyl-6-phenylimadazo
      (4,5-b) pyridine (PhIP) or H2O2 was evaluated by using single-cell
      electrophoresis (comet assay). The toxicity of these tested compounds (0.1-100
      microg/ml) on lymphocytes was not found. These compounds did not cause DNA strand
      breaks at lower concentrations of 0.1-10 microg/ml. At a concentration of 100
      microg/ml, TA and GA exhibited slight DNA damage, whereas PA and EA showed no DNA
      strand breaks. TA and its related compounds decreased the DNA strand breaks
      induced by Trp-P-2, PhIP or H2O2 at concentrations of 0.1-10 microg/ml. DNA
      repair enzymes endonuclease III (Endo III) and formamidopyrimidine-DNA glycoslase
      (FPG)] were used to examine the levels of oxidised pyrimidines and purines in
      human lymphocytes induced by H2O2. All the compounds at 10 microg/ml can reduce
      the level of FPG sensitive sites. However, only EA inhibited the formation of
      EndoIII sensitive sites. The results indicated that these compounds can enhance
      lymphocytes resistance towards DNA strand breaks induced by food mutagens or H2O2
      in vitro.

PMID- 15491635
TI  - Radiation-induced apoptosis of stem/progenitor cells in human umbilical cord
      blood is associated with alterations in reactive oxygen and intracellular pH.
AB  - To investigate the sensitivity of human hematopoietic stem cell populations to
      radiation and its relevance to intracellular events, specifically alteration in
      cellular energy production systems, we examined the frequency of apoptotic cells,
      generation of superoxide anions (O*2-), and changes in cytosol pH in umbilical
      cord blood (UCB) CD34+/CD38-, CD34+/CD38+ and CD34-/CD38+ cells before and after
      5Gy of X-irradiation. Human UCB mononucleated cells were used in this study.
      After X-irradiation and staining subgroups of the cells with fluorescence (FITC,
      PE, or CY)-labeled anti-CD34 and anti-CD38 antibodies, analyses were performed by
      FACScan using as stains 7-amino-actinomycin D (7-AAD) for the detection of
      apoptosis, and hydroethidine (HE) for the measurement of O*2- generation in the
      cells. For intracellular pH, image analysis was conducted using confocal laser
      microscopy after irradiation and staining with carboxy-SNAFR-1. The frequency of
      apoptotic cells, as determined by cell staining with 7-AAD, was highest in the
      irradiated CD34+/CD38- cell population, where the level of O*2- detected by the
      oxidation of HE was also most highly elevated. Intracellular pH measured with
      carboxy-SNARF-1-AM by image cytometer appeared to be lowest in the same
      irradiated CD34+/CD38- cell population, and this intracellular pH decreased as
      early as 4 h post-irradiation, virtually simultaneous with the significant
      elevation of O*2- generation. These results suggest that the CD34+/CD38- stem
      cell population is sensitive to radiation-induced apoptosis as well as production
      of intracellular O*2-, compare to more differentiated CD34+/CD38+ and CD34-/CD38+
      cells and that its intracellular pH declines at an early phase in the apoptosis
      process.

PMID- 15491636
TI  - Relative biological effectiveness of fission neutrons for induction of
      micronucleus formation in mouse reticulocytes in vivo.
AB  - Following whole-body irradiation of ICR mice with various doses of fission
      neutrons or X-rays, the frequency of micronuclei (MNs) in peripheral blood
      reticulocytes was measured at 12 h intervals beginning immediately after
      irradiation and ending at 72 h after irradiation. The resulting time-course curve
      of MN frequency had a clear peak 36 h after irradiation, irrespective of the type
      of radiation applied and the dose used. The MN frequency, averaged as the
      unweighted mean over the experimental time course, showed a linear increase with
      increasing dose of either fission neutrons or X-rays. The linear response to X
      rays supports reported conclusion that induction of MN formation in reticulocytes
      is a dose-rate independent phenomenon. The relative biological effectiveness
      (RBE) of fission neutrons to X-rays for MN induction was estimated to be 1.9 +/-
      0.3. This value is considerably lower than the RBE value of 4.6 +/- 0.5 reported
      for the same fission neutrons for induction of lymphocyte apoptosis in the thymus
      of ICR mice that represents dose-rate independent, one-track event. Based on
      these results, we propose that MNs increased in reticulocytes after irradiation
      mostly represent acentric fragments caused by single chromosome breaks, and that
      some confounding factor is operating in erythroblasts for the formation of
      aberrations from non-rejoining DNA double-strand breaks more severely after high
      LET radiation than after low-LET radiation.

PMID- 15491637
TI  - Increased oxidative DNA damage in mononuclear leukocytes in vitiligo.
AB  - Vitiligo is an acquired pigmentary disorder of the skin of unknown aetiology. The
      autocytotoxic hypothesis suggests that melanocyte impairment could be related to
      increased oxidative stress. Evidences have been reported that in vitiligo
      oxidative stress might also be present systemically. We used the comet assay
      (single cell alkaline gel electrophoresis) to evaluate DNA strand breaks and DNA
      base oxidation, measured as formamidopyrimidine DNA glycosylase (FPG)-sensitive
      sites, in peripheral blood cells from patients with active vitiligo and healthy
      controls. The basal level of oxidative DNA damage in mononuclear leukocytes was
      increased in vitiligo compared to normal subjects, whereas DNA strand breaks
      (SBs) were not changed. This alteration was not accompanied by a different
      capability to respond to in vitro oxidative challenge. No differences in the
      basal levels of DNA damage in polymorphonuclear leukocytes were found between
      patients and healthy subjects. Thus, this study supports the hypothesis that in
      vitiligo a systemic oxidative stress exists, and demonstrates for the first time
      the presence of oxidative alterations at the nuclear level. The increase in
      oxidative DNA damage shown in the mononuclear component of peripheral blood
      leukocytes from vitiligo patients was not particularly severe. However, these
      findings support an adjuvant role of antioxidant treatment in vitiligo.

PMID- 15491638
TI  - Studies on the HPRT mutant frequency in T lymphocytes from healthy Indian male
      population as a function of age and smoking.
AB  - Mutant frequency at the hypoxanthine-guanine phosphoribosyltransferase (HPRT)
      gene in the peripheral blood lymphocytes obtained from 44 healthy individuals (23
      non-smokers and 21 smokers) of an Indian male population was studied using T
      lymphocyte cloning assay. It was found that lnMF increased with age at a rate of
      2.5% per year (P <0.001). Blood samples from smokers showed a significant (P
      <0.037) increase in HPRT mutant frequency (MF) (10.43 +/- 4.74 x 10(-6)) as
      compared to that obtained from non-smokers (7.69 +/- 3.69 x 10(-6)). This study
      also showed a significant (P <0.027) inverse correlation between lnMF and non
      selected cloning efficiency (CE). However, with respect to age no variation was
      observed in cloning efficiency. The results obtained in this study showed a good
      comparison with those reported in different populations of the world.

PMID- 15491639
TI  - Chromosome analysis of mouse one-cell androgenones derived from a sperm nucleus
      exposed to topoisomerase II inhibitors at pre- and post-fertilization stages.
AB  - Mouse spermatozoa and androgenetic one-cell embryos (androgenones) at various
      developmental stages were exposed to etoposide (1 microM), a topoisomerase II
      (topo II) poison, or to either of two catalytic inhibitors: ICRF-193 (10 microM)
      or merbarone (50 microM), for 2 h in order to study the clastogenic effects of
      these drugs on remodeled sperm chromatin. None of the drugs induced structural
      chromosome aberrations in condensed chromatin of spermatozoa. However, etoposide
      and merbarone exerted strong clastogenic actions on remodeled chromatin of
      androgenones. Expanding chromatin was most sensitive to both of these drugs at
      the time of pronuclear formation, as nearly 100% of androgenones exposed at this
      stage displayed structural chromosome aberrations. ICRF-193 did not affect sperm
      chromatin at all remodeling stages. A majority of the aberrations induced by
      etoposide and merbarone were of the chromosome-type. Chromosome exchanges,
      including translocation, dicentric, and ring chromosomes, preferentially appeared
      following exposure at the early stages of chromatin remodeling. Thus, despite
      their different modes of topo II inhibition, etoposide and merbarone showed
      similar clastogenic actions on remodeled sperm chromatin. These results suggest
      that the formation of transient DNA cleavage, mediated by ooplasmic topo II,
      accompanies the remodeling. The present findings provide insight into the
      mechanisms by which structural aberrations are generated in paternal chromosomes.

PMID- 15491640
TI  - Increased mutation in mice genetically predisposed to oxidative damage in the
      brain.
AB  - Harlequin (Hq) mice develop ataxia due to an X-linked recessive mutation in the
      gene encoding apoptosis-inducing factor (Aif). Brain cells in Hq mice contain the
      modified base 8-hydroxydeoxyguanosine (8-OHdG), suggesting that the defect in Aif
      causes increased DNA oxidation in these cells. Because oxidative damage is
      mutagenic, Hq mice might suffer increased mutation in the brain. To examine this
      possibility, mutation in the brain was assessed using the Tg(betaA-G11PLAP) mouse
      model, which allows mutant cells to be visualized in tissue sections in situ. Hq
      mice exhibited more and larger patches of PLAP positive tissue in the brain.
      PLAP+ cells were observed in all areas of the brain. No increase in the number of
      PLAP+ cells was seen in three other tissues, suggesting that the effect of Aif
      deficiency on mutation was specific to brain.

PMID- 15491641
TI  - Larger yield of cyclobutane dimers than 8-oxo-7,8-dihydroguanine in the DNA of
      UVA-irradiated human skin cells.
AB  - Exposure to solar ultraviolet light is the major cause of most skin cancers.
      While the genotoxic properties of UVB radiation are now well understood, the DNA
      damaging processes triggered by less energetic but more abundant UVA photons
      remain to be elucidated. Evidence has been provided for the induction of
      oxidative lesions to cellular DNA including strand breaks and 8-oxo-7,8-dihydro
      2'-deoxyguanosine (8-oxodGuo). Formation of cyclobutane pyrimidine dimers (CPDs)
      has also been reported, mostly in rodent cells. In order to gain insights into
      the relevance of the latter photoproducts in UVA-mutagenesis of human skin, we
      quantified the level of 8-oxodGuo and CPDs within primary cultures of normal
      fibroblasts and keratinocytes using specific chromatographic assays. The yield of
      formation of CPDs was found to be higher than that of 8-oxodGuo in both cell
      types. In addition, CPDs were mostly TT derivatives, and neither (6-4)
      photoproducts nor Dewar valence isomers were detected. These observations are
      reminiscent of results obtained in rodent cells and suggest that a
      photosensitized triplet energy transfer occurs and that this reaction is more
      efficient than photooxidation of DNA components. The predominant formation of
      CPDs with respect to oxidative damage within normal human skin cells exposed to
      UVA radiation should be taken into account in photoprotection strategies.

PMID- 15491642
TI  - Absence of association with cancer risk and low frequency of alterations at a p53
      responsive PIG3 gene polymorphism in breast and lung carcinomas.
AB  - The mechanisms of p53-dependent apoptosis involve a set of genes that possess the
      ability to modulate oxidative stress. One of them PIG3, is induced by p53 through
      a microsatellite in its promoter region. This microsatellite was found to acquire
      its full structure and p53-functional dependence only in Hominoidea (apes and
      humans) and has been proposed to represent an evolutionary adaptation of tumor
      suppressor mechanisms. Microsatellite instability and genetic constitution,
      comprising the presence of the low repetition allele (10 TGYCC repeats), at this
      locus have been hypothesized to provide an increased risk for cancer development.
      Therefore, in the present analysis we examined this polymorphism in two common
      human cancers, lung and breast and compared it with corresponding control cases.
      Furthermore, for lung cancer we employed two different ethnic groups, Greek and
      British. Analysis of this locus in this types of tumors showed: (1) a very low
      frequency of microsatellite instability and loss of heterozygosity (1.4% and 4%,
      respectively) in the examined carcinomas, (2) the homozygous presence of the 10
      repeats allele only in the control cases, and (3) a non-significant increase of
      the most frequent allele (15 repeats) in the cancer groups as compared to control
      ones. The last two observations were found in both Greek and British populations.
      Taken together, these data do not support the notion that this PIG3 polymorphism
      is associated with an increased risk for cancer susceptibility. Larger studies
      including other types of cancer should also be performed.

PMID- 15491643
TI  - MNNG-induced mutations in the adult gill and hepatopancreas and in embryos of
      rpsL transgenic zebrafish.
AB  - To evaluate the feasibility of a mutagenicity assay using adult rpsL transgenic
      zebrafish, 4- to 8-month-old females were exposed to N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG) (0, 15 or 30 mg/L in a water bath for 2 h). At 2 weeks
      after exposure, MNNG showed a concentration-dependent significant increase in
      mutant frequency (MF) of 8 x 10(-5), 18 x 10(-5), and 51 x 10(-5), respectively,
      in the gill. DNA sequencing revealed that 60-74% of the induced mutations were
      G:C to A:T transitions, consistent with the known mutagenic effects of MNNG. A
      marginal but significant increase in MF was observed in the hepatopancreas only
      in the group exposed to 30 mg/L, with the induction of some G:C to A:T
      transitions. A time-course of the appearance of mutations was determined in fish
      treated with 15 mg/L MNNG. In both, the gill and hepatopancreas, a higher MF was
      observed at 3 weeks than at 2 weeks, suggesting that an expression time of at
      least 3 weeks is preferable for the assay. When embryos (29 h post-fertilization)
      were exposed to MNNG (0, 50, and 150 mg/L) for 1 h, MFs increased significantly
      with an increase in the concentration of MNNG (5 x 10(-5), 40 x 10(-5), and 144 x
      10(-5), respectively) at 3 days after exposure. G:C to A:T transitions were the
      predominant mutations, and these occurred at the same sites in the rpsL gene as
      in adult tissues. Thus, MNNG induces typical mutations in the gill and
      hepatopancreas of adult fish, and in embryos, suggesting that the rpsL zebrafish
      is a useful tool for monitoring genotoxicity caused by water-borne mutagens.

PMID- 15491644
TI  - Chromosomal integrity of freeze-dried mouse spermatozoa after 137Cs gamma-ray
      irradiation.
AB  - This study demonstrated that freeze-dried mouse spermatozoa possess strong
      resistance to 137Cs gamma-ray irradiation at doses of up to 8 Gy. Freeze-dried
      mouse spermatozoa were rehydrated and injected into mouse oocytes with an
      intracytoplasmic sperm injection (ICSI) technique. Most oocytes can be activated
      after ICSI by using spermatozoa irradiated with gamma-rays before and after
      freeze-drying. Sperm chromosome complements were analyzed at the first cleavage
      metaphase. Chromosome aberrations increased in a dose-dependent manner in the
      spermatozoa irradiated before freeze-drying. However, no increase in oocytes with
      chromosome aberrations was observed when fertilized by spermatozoa that had been
      irradiated after freeze-drying, as compared with freeze-dried spermatozoa that
      had not been irradiated. These results suggest that both the chromosomal
      integrity of freeze-dried spermatozoa, as well as their ability to activate
      oocytes, were protected from gamma-ray irradiation at doses at which chromosomal
      damage is found to be strongly induced in spermatozoa suspended in solution.

PMID- 15491645
TI  - Are genetic polymorphisms in OGG1, XRCC1 and XRCC3 genes predictive for the DNA
      strand break repair phenotype and genotoxicity in workers exposed to low dose
      ionising radiations?
AB  - Identification of higher risk individuals carrying genetic polymorphisms
      responsible for reduced DNA repair capacity has substantial preventive
      implications as these individuals could be targeted for cancer prevention. We
      have conducted a study to assess the predictivity of the OGG1, XRCC1 and XRCC3
      genotypes and the in vitro single strand break repair phenotype for the induction
      of genotoxic effects. At the population level, a significant contribution of the
      OGG1 genotypes to the in vitro DNA strand break repair capacity was found. At an
      individual level, the OGG1 variants Ser/Cys and Cys/Cys genotypes showed a slower
      in vitro DNA repair than the Ser/Ser OGG1genotype. A multivariate analysis
      performed with genotypes, age, cumulative dose, exposure status and smoking as
      independent variables indicated that in the control population, repair capacity
      is influenced by age and OGG1 polymorphisms. In the exposed population, DNA
      damage is greater in older men and in smokers. Repair capacity is slower in
      individuals with Ser/Cys or Cys/Cys OGG1 genotypes compared to those with the
      Ser/Ser OGG1 genotype. Micronuclei (MN) frequencies increased with age and the
      cumulative dose of gamma-rays. Analysis of the total population revealed that
      genetic polymorphisms in XRCC1 resulted in higher residual DNA (RDNA) values and
      the Met/Met variant of XRCC3 resulted in an increased frequency of micronuclei.
      The analysis confirms that MN frequencies are reliable biomarkers for the
      assessment of genetic effects in workers exposed to ionising radiation (IR). A
      combined analysis of the three genotypes, OGG1, XRCC1 and XRCC3 polymorphisms is
      advised in order to assess individual susceptibility to ionising radiation. As an
      alternative or complement, the in vitro DNA strand break repair phenotype which
      integrates several repair pathways is recommended. Smokers with OGG1
      polymorphisms who are exposed to ionising radiation represent a specific
      population requiring closer medical surveillance because of their increased
      mutagenic/carcinogenic risk.

PMID- 15491646
TI  - Loss of heterozygosity and DNA damage repair in Saccharomyces cerevisiae.
AB  - Loss of heterozygosity (LOH) of tumor suppressor genes is a crucial step in the
      development of sporadic and hereditary cancer. Understanding how LOH events arise
      may provide an opportunity for the prevention or early intervention of cancer
      development. In an effort to investigate the source of LOH events, we constructed
      MATalphacan1Delta::LEU2 and MATa CAN1 haploid yeast strains and examined
      canavanine-resistance mutations in a MATa CAN1/MATalphacan1Delta::LEU2
      heterozygote formed by mating UV-irradiated and nonirradiated haploids. An
      increase in LOH was observed when the irradiated CAN1 haploid was mated with
      nonirradiated can1Delta::LEU2, while reversed irradiation only marginally
      increased LOH. In the rad51Delta background, allelic crossover type LOH increased
      following UV irradiation but not gene conversion. In the rad52Delta background,
      neither type of LOH increased. The chromosome structure following LOH and the
      requirement for Rad51 and Rad52 proteins indicated the involvement of gene
      conversion, allelic crossover and break-induced replication. We argued that LOH
      events could have occurred during the repair of double-strand breaks on a
      functional (damaged) but not nonfunctional (undamaged) chromosome through
      recombination.

PMID- 15491647
TI  - Gene expression spectra in human leukemia HL-60 cells treated with EGCG.
AB  - To decipher the molecular mechanism of EGCG induced HL-60 cell apoptosis,
      alterations of gene expression spectra in HL-60 cell line cells after treatment
      with EGCG were screened by cDNA chip, and analyzed with the GenePix 3.0 twice;
      and the cDNA chip results further identified by RT-PCR. Ninety-seven genes among
      the total 8398 (1.15%) showed consistent significant differential expression in
      the duplicated cDNA chip assessments. Thirty-nine genes (40.2%) were up-regulated
      and 58 genes (59.8%) were down-regulated; and the randomly selected four
      performed RT-PCR results agreed with the cDNA chip data. The results suggest that
      the apoptosis of HL-60 cells induced by EGCG is a progressive transformation
      process regulated by a variety of genes.

PMID- 15491648
TI  - Non-homologous end joining dependency of gamma-irradiation-induced adaptive
      frameshift mutation formation in cell cycle-arrested yeast cells.
AB  - There is a strong selective pressure favoring adaptive mutations which relieve
      proliferation-limiting adverse living conditions. Due to their importance for
      evolution and pathogenesis, we are interested in the mechanisms responsible for
      the formation of such adaptive, gain-of-fitness mutations in stationary-phase
      cells. During previous studies on the occurrence of spontaneous reversions of an
      auxotrophy-causing frameshift allele in the yeast Saccharomyces cerevisiae, we
      noticed that about 50% of the adaptive reversions depended on a functional non
      homologous end joining (NHEJ) pathway of DNA double-strand break (DSB) repair.
      Here, we show that the occasional NHEJ component Pol4, which is the yeast
      ortholog of mammalian DNA polymerase lambda, is not required for adaptive
      mutagenesis. An artificially imposed excess of DSBs by gamma-irradiation resulted
      in a dramatic increase in the incidence of adaptive, cell cycle arrest-releasing
      frameshift reversions. By the use of DNA ligase IV-deficient strains we detected
      that the majority of the gamma-induced adaptive mutations were also dependent on
      a functional NHEJ pathway. This suggests that the same mutagenic NHEJ mechanism
      acts on spontaneously arising as well as on ionizing radiation-induced DSBs.
      Inaccuracy of the NHEJ repair pathway may extensively contribute to the incidence
      of frameshift mutations in resting (non-dividing) eukaryotic cells, and thus act
      as a driving force in tumor development.

PMID- 15491649
TI  - Evidence for induction of DNA double strand breaks in the bystander response to
      targeted soft X-rays in CHO cells.
AB  - This study investigated the role of DNA double strand breaks and DNA base damage
      in radiation-induced bystander responses in Chinese hamster ovary (CHO) cell
      lines. Two CHO repair-deficient clones, xrs5 (DNA double strand break repair
      deficient) and EM9 (DNA base excision repair-deficient) were used in addition to
      the wild type (CHO). The Gray Cancer Institute ultrasoft X-ray microprobe is a
      powerful tool for investigating the bystander response, because it permits the
      irradiation of only a single nucleus of a cell, as reported previously. In order
      to investigate the bystander effect in each repair-deficient cell line, we
      irradiated a single cell within a population and scored the formation of
      micronuclei. When a single nucleus in the population was targeted with 1 Gy,
      elevated numbers of micronuclei were induced in the neighbouring unirradiated
      cells in the EM9 and xrs5 cell lines, whereas induction was not observed in CHO.
      The induction of micronuclei in xrs5 was significantly higher than that in EM9.
      Under these conditions, the surviving fraction in the neighbouring cells was
      significantly lower in xrs5 than in the other cell lines, showing a higher cell
      killing effect in xrs5. To confirm that bystander factors secreted from
      irradiated cells caused these effects, we carried out medium transfer experiments
      using conventional X-irradiation. Medium conditioned for 24 h with irradiated
      cells was transferred to unirradiated cells and elevated induction of micronuclei
      was observed in xrs5. These results suggest that DNA double strand breaks rather
      than base damage are caused by factors secreted in the medium from irradiated
      cells.

PMID- 15491650
TI  - An extension of ASM2d including pH calculation.
AB  - This paper presents an extension of the Activated Sludge Model No. 2d (ASM2d)
      including a chemical model able to calculate the pH value in biological
      processes. The developed chemical model incorporates the complete set of chemical
      species affecting the pH value to ASM2d describing non-equilibrium biochemical
      processes. It considers the system formed by one aqueous phase, in which
      biochemical processes take place, and one gaseous phase, and is based on the
      assumptions of instantaneous chemical equilibrium under liquid phase and
      kinetically governed mass transport between the liquid and gas phase. The ASM2d
      enlargement comprises the addition of every component affecting the pH value and
      an ion-balance for the calculation of the pH value and the dissociation species.
      The significant pH variations observed in a sequencing batch reactor operated for
      enhanced biological phosphorus removal were used to verify the capability of the
      extended model for predicting the dynamics of pH jointly with concentrations of
      acetic acid and phosphate. A pH inhibition function for polyphosphate
      accumulating bacteria has also been included in the model to simulate the
      behaviour observed. Experimental data obtained in four different experiments
      (with different sludge retention time and influent phosphorus concentrations)
      were accurately reproduced.

PMID- 15491651
TI  - Determination of soluble aluminium concentration in alkaline humic water using
      atomic absorption spectrophotometry.
AB  - The steps of the standard method to determine soluble aluminium concentration are
      filtering, followed by acidifying, then analysing with the atomic absorption
      spectrophotometer (AAS). When applied to alkaline humic water, acidification
      gives rise to the formation of humic acid as a brown particulate matter. Of the
      total soluble aluminium in the original water, 49-61% forms complexes with the
      particulate humic acid upon acidification. Although the AAS is capable of
      detecting the binding aluminium, the particulate nature of humic acid easily
      induces inaccurate readings as a result of the non-uniform distribution of the
      particulate matter. A more precise analysis of soluble aluminium concentration of
      alkaline humic water is shown to be achievable in basicified solutions instead.
      Basicified solutions keep humic acid in the soluble form; hence maintain the
      homogeneity of the sample.

PMID- 15491652
TI  - Performance of ion-exchanger grafted textiles for industrial water treatment in
      dynamic reactors.
AB  - The performance of a special class of grafted textiles in removing metal cations
      from industrial wastewaters was examined in continuous reactors. The influence of
      various parameters on the ion exchange process (reactor geometry, inlet metal ion
      concentration, solution flow rate, concentration and type of reagent, etc.) was
      studied over the complete service cycle of the exchanger (saturation, desorption,
      regeneration, rinsing). Dynamic ion exchange characteristics were determined and
      compared with those of resins under identical operating conditions. Higher
      efficiency of fibrous ion exchangers compared to analogous resins, was shown at
      all stages of the service cycle. Results were expressed as a function of
      breakthrough capacity, exchanger utilisation efficiency, volume of solution
      treated, eluted metal concentration. The use of different reactor geometries
      showed two of the many possible applications of grafted textiles in water
      treatment processes.

PMID- 15491653
TI  - Photodegradation of CL-20: insights into the mechanisms of initial reactions and
      environmental fate.
AB  - Hexanitrohexaazaisowurtzitane (HNIW) or CL-20 is a caged structure polycyclic
      nitramine that may replace RDX and HMX as a common use energetic chemical. To
      provide insight into the environmental fate of CL-20 we photolyzed the chemical
      in a Rayonet photoreactor (254-350 nm) and with sunlight in aqueous solutions.
      Previously, we found that initial photodenitration of the monocyclic nitramine
      RDX leads to ring cleavage and decomposition. Presently, we found that photolysis
      of the rigid molecule CL-20 produced NO2-, NO3-, NH3, HCOOH, N2 and N2O. Using
      LC/MS (ES-) we detected several key intermediates carrying important information
      on the initial steps involved in the degradation of CL-20. The identities of the
      intermediates were confirmed using a uniformly ring labeled 15N-[CL-20]. When CL
      20 was photolyzed in the presence of H2(18)O, D2O or 18O2 we obtained a product
      distribution suggesting that the energetic chemical degraded via at least two
      initial routes; one involved sequential homolysis of N-NO2 bond(s) and another
      involved photorearrangement prior to hydrolytic ring cleavage and decomposition
      in water.

PMID- 15491654
TI  - Phosphorus purification in a paddy field watershed using a circular irrigation
      system and the role of iron compounds.
AB  - In a paddy field watershed using a circular irrigation system, it was clear that
      the watershed tended to purify phosphorus by an analysis on the mass balance of
      pollutants. A reasonable hypothesis was that the phosphorus precipitation with
      iron compounds in a river may affect the purification. To verify this, an
      investigation on phosphorus and iron in the river water and sediments were
      conducted. Total iron (T-Fe) concentration in the river ranged from 3 to 10 mg/L,
      and the concentration increased with the river flowing down, whereas dissolved
      iron (D-Fe) concentrations tended to decrease. The concentrations of total
      phosphorus (T-P) and phosphate phosphorus (PO4-P) also tended to decrease as the
      river flowing down. From the analysis of mass balance, the study watershed was
      considered to be a substantial iron source, having 307 and 206 kg/ha of annual
      outflow loads. In the sediment of the river, T-P ranged from 834 to 2440
      microg/g, and most of the inorganic compound was Fe-P. In addition, The Bray No.2
      phosphorus (441-1030 microg/g) was much higher than in paddy soils. Therefore,
      the sediment contained a large amount of phosphorus and was fertile. From the
      results of laboratory-based experiments, it can be said that iron compounds in
      the river were sufficient for the precipitation of phosphorus. Since the
      accumulated sediment in the river was conventionally dredged up and transported
      to adjacent paddy fields, it was considered to be that this operation played a
      significant role in phosphorus resource recycling.

PMID- 15491655
TI  - A rapid method to measure the solid-water distribution coefficient (Kd) for
      pharmaceuticals and musk fragrances in sewage sludge.
AB  - Pharmaceuticals and personal care products are omnipresent in wastewater world
      wide. In order to predict their sorption quantities onto sludge in wastewater
      treatment plants (WWTPs), the solid-water distribution coefficients (Kd values)
      of selected pharmaceuticals (antiphlogistics, estrogens, lipid regulators, anti
      epileptic and cytostatic agents) and polycyclic musk fragrances (HHCB, AHTN) were
      determined in primary and secondary sludges taken from a German municipal WWTP.
      For the Kd determination, batches of primary and secondary sludge slurries were
      spiked with the respective target compounds and slowly stirred under defined
      conditions (e.g. an argon atmosphere). Finally, the water and solid sludge phases
      were analysed. The Kd values of pharmaceuticals ranged from <1 to 500 L kg(-1),
      while those for the polycyclic musk fragrances AHTN and HHCB proved to be up to
      5300 and 4900 L kg(-1), respectively. The primary and secondary sludge showed
      significant differences for some pharmaceuticals such as Diclofenac and
      Cyclophosphamide due to the different pH and composition of the two sludges. The
      removal rate from the water phase caused by sorption in a WWTP can be reasonably
      predicted on the basis of the Kd values.

PMID- 15491656
TI  - Aspects of decision support in water management--example Berlin and Potsdam
      (Germany) II--improvement of management strategies.
AB  - Methods related to partial order theory such as the Hasse diagram technique (HDT)
      are increasingly used in the field of multi-criteria decision support. The HDT
      has the advantage of being a transparent evaluation tool, supported by several
      data analysis tools such as the concept of antagonistic indicators. However, the
      evaluation usually does not lead to a clear decision, because more than one
      possible solution is offered. In the example presented here, three of the nine
      water management strategies (scenarios) evaluated by HDT were identified as
      winners. However, these strategies were not comparable with each other because of
      the conflicting evaluation of at least two different indicators. Such antagonisms
      describe the advantage and disadvantage of each scenario. Based on this
      background information, a new innovative approach is demonstrated, enabling the
      stakeholders to design new, modified management strategies, with reduced negative
      effects. After improvement of the three potential solutions, one clear winner
      scenario could be identified.

PMID- 15491657
TI  - A predictive model for the reactor inorganic suspended solids concentration in
      activated sludge systems.
AB  - A simple predictive model for the activated sludge reactor inorganic suspended
      solids (ISS) concentration (excluding that from chemical precipitant dosing) is
      presented. It is based on the accumulation of influent ISS in the reactor and an
      ordinary heterotrophic organism (OHO) ISS content (fiOHO) of 0.15 mg ISS/mg OHO
      organic (volatile) suspended solids (VSS) and a variable phosphate accumulating
      organism (PAO) ISS content (fiPAO) proportional to their P content (fXBGP).
      Organism ISS content is conceptualized as the uptake of dissolved inorganic
      solids by active organisms, which when dried in the total suspended solids (TSS)
      test procedure, precipitate and manifest as ISS. The model is validated with data
      from 22 investigations conducted over the past 15 years on 30 aerobic and anoxic
      aerobic nitrification-denitrification (ND) systems and 18 anaerobic-anoxic
      aerobic ND biological excess P removal (BEPR) systems variously fed artificial
      and real wastewater, and operated from 3 to 20 days sludge age. The predicted
      reactor VSS/TSS ratio reflects the observed relative sensitivity to sludge age,
      which is low, and to BEPR, which is high. To use the model for design, two
      parameters need to be known: (1) the influent ISS concentration, which is not
      commonly measured in wastewater characterization analyses and (2) the P content
      of PAOs (fXBGP), which can vary considerably depending on the extent of anoxic P
      uptake BEPR that takes place in the system. Some guidance on the measurement of
      influent ISS concentration and selection of the PAO P content to calculate the
      mixed liquor VSS/TSS ratio for design is given.

PMID- 15491658
TI  - Photooxidation of bisphenol A (BPA) in water in the presence of ferric and
      carboxylate salts.
AB  - In this work, the photooxidation of bisphenol A (BPA), a suspected endocrine
      disruptor (ED), in water in the presence of ferric and oxalate ions was
      investigated in a concentric reactor under a 125 W high-pressure mercury lamp
      (lambda> or = 365 nm). The photooxidation efficiencies were dependent on the pH
      values and ferric/oxalate concentration ratios (Fe(III)/Ox) in the water, with
      higher efficiency at pH 3.50+/-0.05 and Fe(III)/Ox 10.0/120.0 micromol l(-1). The
      initial rate of photooxidation increases with increasing the initial
      concentration of BPA from 2.0 to 5.0 mg l(-1) while do not change at 5.0 and 10.0
      mg l(-1). However, higher removal efficiency of BPA is archived at lower BPA
      initial concentration over range of 2.0 to 10.0 mg l(-1). For 2.0 mg l(-1) BPA,
      the initial rate of photooxidation is 0.06 mg l(-1)min(-1). By using UV-Vis
      spectrum and LC-MS techniques, the predominant photooxidation product BPA-o
      catechol was identified and the mechanisms for the oxidative degradation were
      proposed. When BPA reacted with OH radicals, C atoms in 3-position were added
      with OH radicals followed by O2 peroxidation and HO2 radical escape. Then
      catechol derivatives were produced. After that, the two H atoms on the hydroxy
      group were extracted in two individual steps to form intermediates semiquinone
      radical and o-quinone. The intermediates underwent further oxidation, benzene
      ring cleavage and decarboxylation, up to mineralization ultimately.

PMID- 15491659
TI  - Influence of the agitation rate on the treatment of partially soluble wastewater
      in anaerobic sequencing batch biofilm reactor.
AB  - This work reports on the influence of the agitation rate on the organic matter
      degradation in an anaerobic sequencing batch reactor, containing biomass
      immobilized on 3 cm cubic polyurethane matrices, stirred mechanically and fed
      with partially soluble soymilk substrate with mean chemical oxygen demand (COD)
      of 974+/-70 mg l(-1). Hydrodynamic studies informed on the homogenization time
      under agitagion rates from 500 to 1100 rpm provided by three propeller impellers.
      It occurred very quickly compared to the total cycle time. The results showed
      that agitation provided good mixing and improved the overall organic matter
      consumption rates. A modified first-order kinetic model represented adequately
      the data in the entire range of agitation rate. The apparent first-order kinetic
      constant for suspended COD rose approximately 360% when the agitation rate was
      changed from 500 to 900 rpm, whereas the apparent first-order kinetic constant
      for soluble COD did not vary significantly.

PMID- 15491660
TI  - Pilot studies for in-situ aerobic cometabolism of trichloroethylene using toluene
      vapor as the primary substrate.
AB  - In-situ pilot studies of aerobic cometabolism were conducted to evaluate the
      injection of toluene-vapor and air into TCE-contaminated aquifer. Delivery of
      primary substrate (toluene) in a vapor state with air enhanced the growth of
      indigenous toluene-utilizing bacteria that would degrade TCE by aerobic
      cometabolism. Meanwhile, delivering toluene in a vapor state effectively reduced
      potential clogging near the injection points due to excessive microbial growth,
      which was observed in the field when the injection of neat toluene was employed.
      Over 90% removal of TCE was achieved with primary substrate (toluene) degraded to
      a concentration below 10 microg/L.

PMID- 15491661
TI  - Isolation and characterization of a bacterium capable of removing taste- and odor
      causing 2-methylisoborneol from water.
AB  - 2-Methylisoborneol (MIB), a metabolite of blue-green algae, has been implicated
      in causing unpalatable drinking water throughout the world. Current non
      biological water treatment technologies are ineffective in removing MIB from
      potable water or are cost-prohibitive, and biological applications may address
      these problems. We have isolated and characterized a bacterium derived from lake
      water and capable of aerobically degrading MIB. Light microscopy and transmission
      electron microscopy revealed that this strain is a spore-forming, flagellated
      bacterium that is bacilloid in shape, and 16S rRNA phylogenetic analysis
      determined that it is most closely related to Bacillus fusiformis and Bacillus
      sphaericus, both members of the Bacillus sphaericus senso lato taxon. While the
      growth and oxidation potential of this strain was shown to be affected beyond
      certain MIB concentrations in the mg/l range, it was capable of depleting MIB at
      mg/l and ng/l concentrations and of removing MIB to concentrations yielding no
      observed odor.

PMID- 15491662
TI  - Evaluation of solid-state bioconversion of domestic wastewater sludge as a
      promising environmental-friendly disposal technique.
AB  - Natural and environmental-friendly disposal of wastewater sludge is a great
      concern. Recently, biological treatment has played prominent roles in
      bioremediation of complex hydrocarbon- rich contaminants. Composting is quite an
      old biological-based process that is being practiced but it could not create a
      great impact in the minds of concerned researchers. The present study was
      conducted to evaluate the feasibility of the solid-state bioconversion (SSB)
      processes in the biodegradation of wastewater sludge by exploiting this promising
      technique to rejuvenate the conventional process. The Indah Water Konsortium
      (IWK) domestic wastewater treatment plant (DWTP) sludge was considered for
      evaluation of SSB by monitoring the microbial growth and its subsequent roles in
      biodegradation under two conditions: (i) flask (F) and (ii) composting bin (CB)
      cultures. Sterile and semi-sterile environments were allowed in the F and the CB,
      respectively, using two mixed fungal cultures, Trichoderma harzianum with
      Phanerochaete chrysosporium 2094 (T/P) and T. harzianum with Mucor hiemalis (T/M)
      and two bulking materials, sawdust (SD) and rice straw (RS). The significant
      growth and multiplication of both the mixed fungal cultures were reflected in
      soluble protein, glucosamine and color intensity measurement of the water
      extract. The color intensity and pH of the water extract significantly increased
      and supported the higher growth of microbes and bioconversion. The most
      encouraging results of microbial growth and subsequent bioconversion were
      exhibited in the RS than the SD. A comparatively higher decrease of organic
      matter (OM) % and C/N ratio were attained in the CB than the F, which implied a
      higher bioconversion. But the measurement of soluble protein, glucosamine and
      color intensity exhibited higher values in the F than the CB. The final pH drop
      was higher in the CB than the F, which implied that a higher nitrification
      occurred in the CB associated with a higher release of H+ ions. Both the mixed
      cultures performed almost equal roles in all cases except the changes in moisture
      content.

PMID- 15491663
TI  - Seasonal first flush phenomenon of urban stormwater discharges.
AB  - California's climate, typified by winter and spring precipitation and summer
      drought, is often called a Mediterranean climate, and creates a long period for
      pollutant build-up. The initial storms of the winter season usually have higher
      pollutant concentrations, which is called a seasonal first flush. To investigate
      the existence of a seasonal first flush, we analyzed four major data sets,
      collected over the 1999-2000 to 2002-2003 wet seasons. Trends in seasonal loads
      were quantified by plotting pollutant concentrations or cumulative pollutant load
      versus cumulative rainfall or cumulative runoff volume. Pollutant concentrations
      in the first part of the wet season were ranged from 1.2 to 20 times higher than
      concentrations near the end of the season, and mass emission rates were similarly
      higher at the beginning of the season. A seasonal first flush existed for most
      cases and was strongest for organics, minerals and heavy metals except lead. This
      result suggests that applying treatment Best Management Practices (BMPs) early in
      the season could remove several times more pollutant mass than randomly timed or
      uniformly applied BMPs.

PMID- 15491664
TI  - Fouling mechanisms in the integrated system with softening and ultrafiltration.
AB  - Softening is designed to remove hardness ions, but it can also remove NOM and
      particles, yielding the possibility to use the process as a pretreatment for
      ultrafiltration. The objectives of this research were to understand the nature of
      the fouling mechanisms for ultrafiltration when used for waters that either
      require softening or have been softened, and to use that understanding to
      determine promising options for the use of softening as a pretreatment before
      ultrafiltration. To understand fouling mechanisms in the integrated system with
      softening and ultrafiltration, three different levels of softening performance in
      terms of removal of inorganics and organic matter were selected. Experiments were
      performed with both natural waters and synthetic waters with similar (but
      separable) inorganic, organic, and particulate characteristics. The synthetic
      waters were used to distinguish among inorganic fouling by precipitates, organic
      fouling, particulate fouling, and combined fouling by particles and organic
      matter. The results showed that organic matter played a major role in fouling,
      either by itself or by adsorption onto particles, and that softening pretreatment
      effectively reduced the foulants prior to ultrafiltration.

PMID- 15491665
TI  - Fate of perchlorate-contaminated water in upflow wetlands.
AB  - The potential of natural wetland systems to treat perchlorate-contaminated water
      was investigated in vertical upflow wetland columns planted with and without
      Bulrush (Scirpus sp.). In the absence of nitrate (NO3- -N <1mg/L), wetland
      columns were capable of removing ClO4- to levels below the detection limit (<4
      microg/L) for a series of influent ClO4- (4, 8, 16, and 32 mg/L). At an influent
      ClO4- concentration of 32 mg/L, ClO4- breakthrough was observed with the increase
      in nitrate concentration. ClO4- and NO3- degradation rate constants (Kpc and KNO3
      -N) were also determined using a 1-D transport model with dispersion. Kpc
      declined with the increase of influent ClO4- and NO3- -N concentration (6.49-0.42
      day(-1) for unplanted columns, and 7.80-0.21 day(-1) for planted columns,
      respectively). KNO3- -N followed similar trends but was relatively higher than
      Kpc. Plant uptake was directly linked with ClO4- concentration in the
      rhizosphere, and the stem bio-concentration factor (BCF) was estimated to be 57.
      A mass balance indicated plant uptake accounted for 0-14.3% of initial ClO4-
      input. Microbial degradation played a more important role than plant uptake and
      transformation in ClO4- degradation in this wetland system. This study suggests
      that constructed wetlands may be a promising technology to treat perchlorate
      contaminated waters.

PMID- 15491666
TI  - Chemical characterisation of natural organic substrates for biological mitigation
      of acid mine drainage.
AB  - The current approach of the biological treatment of acid mine drainage by means
      of a passive remediation system involves the choice of an appropriate organic
      substrate as electron donor for sulphate reducers. Nowadays this selection is one
      of the critical steps in the performance of such treatment, as this depends to a
      great extent on the degradability of the organic substrate. Thus, a prior
      characterisation of the organic substrate predicting its biodegradability would
      be desirable before embarking on an extensive large-scale application. The aim of
      this study was to correlate the chemical composition (lignin content) of four
      different natural organic substrates (compost, sheep and poultry manures, oak
      leaf) and their capacity to sustain bacterial activity in an attempt to predict
      biodegradation from chemical characterisation. The results showed that the lower
      the content of lignin in the organic substrate, the higher its biodegradability
      and capacity for developing bacterial activity. Of the four organic materials,
      sheep and poultry manures and oak leaf evolved reducing conditions and sustained
      active sulphidogenesis, which coupled with the decrease in sulphate concentration
      indicated bacterial activity. Sheep manure was clearly the most successful
      organic material as electron donor (sulphate removal >99%), followed by poultry
      manure and oak leaf (sulphate removal of 80%). Compost appeared to be too poor in
      carbon to promote sulphate-reducing bacteria activity by itself. Column
      experiments emphasised the importance of considering the residence time as a key
      factor in the performance of continuous systems. With a residence time of 0.73
      days, sheep manure did not promote sulphidogenesis. However, extending residence
      time to 2.4 and 9.0 days resulted in an increase in the sulphate removal to 18%
      and 27%, respectively.

PMID- 15491667
TI  - Photocatalysis of p-chlorobenzoic acid in aqueous solution under irradiation of
      254 nm and 185 nm UV light.
AB  - The photolytic and photocatalytic degradation of p-chlorobenzoic acid (p-CBA) in
      aqueous solution were investigated using two kinds of low-pressure mercury lamps:
      one emitted at 254 nm and the other emitted at 254 nm and 185 nm. Both the
      photolytic and photocatalytic degradations of p-CBA followed pseudo first-order
      reaction rate form. The rate constants decreased with increase of initial
      concentration in VUV and TiO2/VUV. The TiO2/VUV was the most efficient process,
      in which rate constants was 3.0-6.5 times as that in TiO2/UV depending on the
      initial concentration. The gas bubbling efficiently improved the mass transfer
      and the kind of bubbling gas had evident influence on the reaction rate except in
      UV photolysis. TOC reduction rate was greatly reduced in VUV and TiO2/VUV
      processes when bubbled with nitrogen gas, it was no more than one third of that
      when bubbled with oxygen, however, the degradation rate of p-CBA was not affected
      by bubbled nitrogen so greatly.

PMID- 15491668
TI  - Degradation of alkyllead compounds to inorganic lead in contaminated soil.
AB  - In glass columns with sandy soil from a former antiknocking agents factory
      hydrophobic tetraalkyllead was transformed in oxygen-saturated water to inorganic
      lead. Up to 324 mg l(-1) trialkyllead, but only very little dialkyllead
      accumulated. After 740 days 49.1+/-6.7% of the organic lead was converted to
      inorganic lead. Conversion of hydrocarbons was 39.6+/-5.1%. To reduce toxicity of
      high trialkyllead concentrations the water of soil columns was replaced by tap
      water after 450d. Trialkyllead in the new water increased again to more than 150
      mg l(-1). If the alkyllead-containing water from these columns was diluted to
      concentrations of alkyllead compounds that were found in the groundwater after
      air injection (total alkyllead<10 mg l(-1)) and used as a source of alkyllead
      compounds in columns with non-contaminated sandy soil, elimination of tetra-, tri
      and dialkyllead compounds followed first-order kinetics. In the soil 85.8-93.6%
      of the alkyllead dissappeared in only 170 days with 51% being converted to
      inorganic lead. This makes in situ remediation reasonable.

PMID- 15491669
TI  - A study of the reaction mechanisms of the degradation of 2,4
      dichlorophenoxyacetic acid by oxalate-mediated photooxidation.
AB  - The oxidation of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) by
      FeII/H2O2/UV (FHU) and ferrous-oxalate/H2O2/UV (FOHU) processes was investigated
      and compared. The initial decay rate and the overall removal percentage were used
      as the performance indexes. To extensively explore the associated processes, the
      intermediates and the end products were also examined and compared. The results
      showed that the degradation of 2,4-D by FHU is slower than that of FOHU. The
      involvement of ferrous-oxalate in the reaction can greatly improve the initial
      decay rate of 2,4-D because of the higher light sensitivity of the organometallic
      complexes. The total removal of 2,4-D and its corresponding intermediates was
      found to be strongly dependent on the initial hydrogen peroxide concentration; an
      excessively low initial [H2O2] will terminate the process due to the deficiency
      of hydroxyl radicals in the solution. All of the major primary intermediates (2,4
      dichlorophenol, 2-chloro-4-hydroxyphenoxyacetic acid, 4-chloro-2
      hydroxyphenoxyacetic acid, 5-hydroxy-2,4-dichlorophenoxyacetic acid and 6-hydroxy
      2,4-dichlorophenoxyacetic acid) have been identified and confirmed by LC-MS. A
      reaction mechanism was proposed for FHU and FOHU and verified by the evidence
      presented in this study.

PMID- 15491670
TI  - Recent advances in removing phosphorus from wastewater and its future use as
      fertilizer (1997-2003).
AB  - Large quantities of phosphate present in wastewater is one of the main causes of
      eutrophication that negatively affects many natural water bodies, both fresh
      water and marine. It is desirable that water treatment facilities remove
      phosphorus from the wastewater before they are returned to the environment. Total
      removal or at least a significant reduction of phosphorus is obligatory, if not
      always fulfilled, in most countries. This comprehensive review summarizes the
      current status in phosphorus-removal technologies from the most common
      approaches, like metal precipitation, constructed wetland systems, adsorption by
      various microorganisms either in a free state or immobilized in polysaccharide
      gels, to enhanced biological phosphorus removal using activated sludge systems,
      and several innovative engineering solutions. As chemical precipitation renders
      the precipitates difficult, if not impossible, to recycle in an economical
      industrial manner, biological removal opens opportunities for recovering most of
      the phosphorus and beneficial applications of the product. This review includes
      the options of struvite (ammonium-magnesium-phosphate) and hydroxyapatite
      formation and other feasible options using, the now largely regarded contaminant,
      phosphorus in wastewater, as a raw material for the fertilizer industry. Besides
      updating our knowledge, this review critically evaluates the advantage and
      difficulties behind each treatment and indicates some of the most relevant open
      questions for future research.

PMID- 15491671
TI  - Sonochemical decomposition of volatile and non-volatile organic compounds--a
      comparative study.
AB  - Sonochemical degradation which combines destruction of the target compounds by
      free radical reaction and thermal cleavage is one of the recent advanced
      oxidation processes (AOP) and proven to be effective for removing low
      concentration organic pollutants from aqueous streams. This work describes the
      degradation of several organic compounds of varying volatility in aqueous
      solution in two types of ultrasonic reactors. The process variables studied
      include initial concentration of the organics, temperature, and type of saturated
      gas. The effects of additional oxidant and electrolyte were also examined. A
      kinetic model was tested to determine its ability to predict the degradation rate
      constant of different volatile organic compounds at different initial conditions.
      A figure of merit for the electrical energy consumption for the two types of
      ultrasonic reactors is also presented.

PMID- 15491672
TI  - Biofilm and biomass characteristics in high-performance fluidized-bed biofilm
      reactors.
AB  - Two laboratory-scale fluidized-bed biofilm reactors (FBBRs) were used to
      investigate the biomass concentration and the biofilm characteristics in a high
      performance FBBR used for the denitrification of exceptionally high-nitrate
      wastewater (1000 mg N/L). Reported correlations by other workers for predicting
      the biomass concentration in FBBR were examined for their validity in comparison
      with the experimental results of this study and the best set of applicable
      correlations was recommended. The effects of the two main operational parameters,
      the superficial velocity and nitrogen loading rate on the biomass concentration
      in the FBBR were also studied. Correlations for the drag coefficient and the
      expansion index from the literature, together with the biofilm dry density
      correlation produced from this study were found to produce the best prediction of
      the FBBR biomass concentration compared to other reported correlations. The
      average biomass concentration in the FBBR decreased with the increase of the
      superficial velocity in the range of 45-65 m/h at all applied nitrogen loadings
      (i.e. 6, 8, 12 and 16 kg N/m3bedd).

PMID- 15491673
TI  - In-line coagulation with low-pressure membrane filtration.
AB  - The objectives were to investigate the effects of in-line coagulation on removal
      of natural organic matter (NOM) and turbidity and on fouling of membranes during
      ultrafiltration (UF). Coagulants were added prior to UF, without intermediate use
      of conventional processes for removal of particles. Synthetic and natural raw
      waters were examined. Charge neutralization, sweep floc, and under-dose
      conditions (with respect to conventional treatment) were all effective for
      removal of NOM and turbidity by UF. Most coagulation conditions resulted in
      decreased resistance to filtration and improved hydraulic removal of filter cake,
      including conditions that would be ineffective prior to conventional settling and
      rapid-filtration. Flocs that were produced under charge neutralization conditions
      and acidic under-dose conditions produced lower hydraulic resistance and were
      less compressible than for sweep floc conditions.

PMID- 15491674
TI  - Chemistry and nanoparticulate compositions of a 10,000 year-old ice core melt
      water.
AB  - Particulates extracted from a single section of a 10,000 year-old ice core melt
      sample exhibited characteristics of contemporary, airborne fine particulates: a
      majority were microcrystalline particulates and aggregated microcrystals,
      including some mixtures of microcrystals and carbonaceous matter. Particularly
      significant were the presence of carbon nanotubes and fullerene nanocrystals
      composing aggregated particulates reflecting global combustion products similar
      to contemporary, airborne carbon nanocrystal aggregates. ICP elemental analysis
      of the melt water showed significant concentrations of Ca, K and especially Na
      (corresponding to K, NaCl), S, Si, Se, and Zn. Overall, the elemental analysis of
      the melt water is similar to local tap water. However, lead was absent in the
      local tap water and only half the concentration of selenium was present in the
      tap water in contrast to the ice core water. While these observations cannot be
      generalized, the methodology illustrates the potential to characterize and
      compare airborne particulate regimes and water chemistries in antiquity.

PMID- 15491675
TI  - Age-promoted creation of a pro-cancer microenvironment by inflammation:
      pathogenesis of dyscoordinated feedback control.
AB  - Aging and local chronic inflammation are established risk factors for epithelial
      tumorigenesis. These risk factors can act individually and/or synergistically to
      increase the incidence of age-related carcinomas. The basis for this co
      stimulatory response has not yet been defined, nor have the feedback mechanisms
      that are responsible for this synergism. This review provides insight into the
      age-stimulated dysregulation of coordination of feedbacks in oxygen-, heme-, and
      proteolysis-dependent metabolic pathways caused by acute and chronic
      inflammation, and its role as a possible pathological basis for the creation of a
      pro-cancer microenvironment (PCM). The PCM facilitates the selective survival and
      growth of transformed cells (in a manner similar to a cancer-supportive
      microenvironment (CM)). The cancer-induced environment has certain features in
      common with chronic inflammatory-induced PCM. Namely, there are: enhanced
      oxidative cell resistance against apoptosis, increased production of matrix
      degrading enzymes, switching to glycolytic metabolism, angiogenesis and
      vasorelaxation thus providing nutrient delivery, but restriction of the immune
      cell mobilization and/or its activation. The hypothetical model of PCM-genesis is
      presented as a result of enzymatic dysregulation of feedback control including
      oxygen-, heme-, prostaglandin E(2)-, metalloproteinase-9-, and NO/CO-dependent
      pathways. PCM-genesis takes place between the growth-inhibiting (cytotoxic) and
      growth promoting (regenerative) stages of inflammatory response. According to
      this model, age-related metabolic changes create opportunities for chronic (not
      acute) inflammatory response, which supports the PCM-condition with the non
      healing wound state that often occurs around carcinomas.

PMID- 15491676
TI  - Role of sirtuin proteins in life extension by caloric restriction.
AB  - The deacetylase activity of sirtuin proteins may play a key role in the life
      extending action of caloric restriction in organisms ranging from yeast to
      mammals. Recent research has been focused on the possible afferent pathway by
      which caloric restriction increases the deacetylase activity and on the efferent
      pathway by which the increased deacetylase activity extends life. Further
      research is needed to firmly establish the role of sirtuin proteins in life
      extension by caloric restriction in mammals.

PMID- 15491677
TI  - CD28 activation does not down-regulate Cbl-b expression in aged rat T
      lymphocytes.
AB  - It is well known that T-lymphocyte proliferation declines ex vivo with age, and
      is associated with decreased expression and/or activity of stimulatory
      intracellular signaling proteins. However, the role of inhibitory intracellular
      signaling molecules like the ubiquitin ligase Cbl-b in regulating T-lymphocyte
      function in aging is largely unknown. Therefore, we tested the hypothesis that T
      lymphocyte proliferation declines with age, in part, due to increased expression
      of Cbl-b. We show that young splenic T-lymphocytes reduced Cbl-b expression when
      stimulated with anti-CD3 and anti-CD28 antibodies, while in aged T-lymphocytes
      the CD28-dependent Cbl-b down-regulation did not occur. This effect did not
      appear to be due to reduced CD28 receptor expression on aged T-lymphocytes. The
      mechanism for lack of Cbl-b down-regulation may involve the proteasome since
      blocking proteasomal activity in young T-lymphocytes prevented Cbl-b down
      regulation while there was no effect in aged T-lymphocytes on Cbl-b expression.
      These data provide evidence for a novel mechanism by which aging reduces T
      lymphocyte function.

PMID- 15491678
TI  - A Paramecium tetraurelia mutant that has long autogamy immaturity period and
      short clonal life span.
AB  - We have isolated an unprecedented mutant of Paramecium tetraurelia that has a
      long immaturity period until autogamy. This mutant stock, d4-RK, screened for 0%
      autogamy at the age of 27 fissions, began to undergo autogamy around the age of
      50 fissions in some clones and underwent autogamy scarcely even after the age of
      100 fissions in others. d4-RK expressed its mutant phenotype at 25 degrees C, but
      resembled the wild-type phenotype at 32 degrees C. Genetic analyses indicated
      that a single recessive gene, named rie (remote immaturity exit), was responsible
      for the mutant phenotype. This is the first report to show a gene that elongates
      the time to sexual maturation in unicellular organisms. The clonal life span was
      shorter and fission rate was lower in the rie mutant than in the wild-type, both
      at 25 degrees C and 32 degrees C. Even in the fourth autogamous generation
      following the third backcross to the wild-type, the progeny with the elongated
      autogamy immaturity period still had a short clonal life span and low fission
      rate, while those with the wild-type phenotype in autogamy immaturity period
      showed the wild-type phenotypes in clonal life span and fission rate, too.

PMID- 15491679
TI  - Age-associated changes in the frequency of naive, memory and effector CD8+ T
      cells.
AB  - We investigated age-associated changes in the frequency of CD8+ T cell subsets
      with different functions. Based on expression of CD45RA and CCR7, naive (CD45RA+
      CCR7+), central memory (CM, CD45RA- CCR7+), effector memory (EM, CD45RA- CCR7-)
      and effector (CD45RA+ CCR7-) CD8+ T cells were identified in peripheral blood
      from healthy young (n = 17) and elderly (n = 17) people using flow cytometry. The
      elderly had a decreased frequency of naive and an increased frequency of EM and
      effector CD8+ T cells compared to the young. However, both groups had a similar
      frequency of CM cells. These findings suggest that age-associated changes in CD8+
      T cell subsets occur, which could be a potential explanation for altered CD8+ T
      cell function in the elderly.

PMID- 15491680
TI  - Myofibrillar myosin ATPase activity in hindlimb muscles from young and aged rats.
AB  - We tested the hypothesis that Ca(2+)-activated myosin ATPase activity is lower in
      muscles of aged rats relative to muscles of young rats, independent of changes in
      myosin isoform expression. Myofibrils were prepared from permeabilized fibers of
      soleus, plantaris, and semimembranosus muscles of young (8-12 months) and aged
      (32-38 months) F344 x BN rats and assayed for resting myosin ATPase, Ca(2+)
      activated myosin ATPase, and myosin heavy chain (MHC) and myosin light chain
      (MLC) isoform compositions. Resting myosin ATPases were not affected by age in
      any muscle (P > or = 0.42). Ca(2+)-activated myosin ATPases of soleus and
      plantaris myofibrils were not affected by age (P > or = 0.31) but were 16% lower
      in semimembranosus myofibrils from aged rats (0.448 +/- 0.019 micromol
      P(i)/min/mg) compared to young rats (0.533 +/- 0.031 micromol P(i)/min/mg; P =
      0.03). Correspondingly, maximal unloaded shortening velocity of single
      semimembranosus fibers from aged rats was slow (4.6 +/- 0.2 fiber lengths/s)
      compared with fibers from young rats (5.8 +/- 0.3 fiber lengths/s; P < 0.01). No
      age-related changes in MHC or regulatory MLC isoforms were detected in any muscle
      (P > or = 0.08) but changes in the essential MLC occurred in plantaris and
      semimembranosus muscles. The data indicate that Ca(2+)-activated myosin ATPase
      activity is reduced with age in semimembranosus muscle, independent of age
      related changes in MHC isoform expression, and is one mechanism contributing to
      age-related slowing of contraction in that muscle.

PMID- 15491681
TI  - Statistical methods for testing effects on "maximum lifespan".
AB  - It has been noted that certain interventions such as caloric restriction may
      increase maximum lifespan, whereas other interventions may increase mean or
      median lifespan but not maximum lifespan. Here the term "maximum lifespan" is
      used to refer to the upper percentiles of the distribution of lifespan. This is
      of great interest because increasing maximum lifespan may be an indicator that an
      intervention is slowing the general process of aging and not merely retarding the
      development of specific diseases. However, formal methods for testing maximum
      lifespan have not been elucidated. Herein, we show via simulation that
      conditional t-test (CTT), a method that is sometimes used, is invalid. We then
      offer a new method based on quantile regression and we show that this method is,
      at worst, conservative and remains powerful and valid.

PMID- 15491682
TI  - Mechanisms underlying the impaired regulation of 3-hydroxy-3-methylglutaryl
      coenzyme A reductase in aged rat liver.
AB  - As the main risk factor for cardiovascular disease, hypercholesterolemia is one
      of the most studied age-related metabolic alterations. In the liver, cholesterol
      homeostasis is strictly regulated through the modulation of the 3-hydroxy-3
      methylglutaryl coenzyme A reductase (HMG-CoA reductase), the key enzyme of
      cholesterol biosynthesis. With ageing, hepatic HMG-CoA reductase becomes
      completely activated and cholesterol content increases in the blood. The research
      reported in this paper uses the regulatory enzymes of reductase (i.e., the AMP
      dependent kinase (AMPK) and the protein phosphatase 2A (PP2A)), the HMG-CoA
      reductase thermodependent activity and the "in vitro" enzyme degradation to
      elucidate the role played by the HMG-CoA reductase regulation and its membrane
      interaction. Related experiments were performed on 3 and 24 months "ad libitum"
      (AL) fed rats and 24 months caloric-restricted rats. The results show no changes
      in the PP2A level and the activation state of AMP dependent kinase in aged "ad
      libitum" fed rats. By contrast, the activation state of the kinase is enhanced in
      the aged caloric-restricted animals. With respect to the adult, the
      thermodependent activity of reductase remains unchanged, while the degradation
      rate of the HMG-CoA reductase is slower and independent on proteasome. These
      findings support the hypothesis that a different arrangement of the HMG-CoA
      reductase membrane domain in aged rats is a cause of reductase deregulation.

PMID- 15491683
TI  - Cellular cholesterol enrichment impairs T cell activation and chemotaxis.
AB  - Human aging is associated with an increase in immune cell cholesterol levels,
      independent of circulating cholesterol levels. The effects of such an increase in
      membrane cholesterol on lipid raft-associated immune cell function have not been
      investigated. We sought to examine the effects of in vitro cholesterol loading on
      two known lipid raft-associated pathways of T cells, namely T cell activation and
      chemokine stimulation. Using beta-cyclodextrin (BCD) as a vehicle, we were able
      to rapidly load cholesterol onto human T cell lines and primary peripheral blood
      T cells without inducing significant cell toxicity. Loading of cholesterol to
      four-fold that of normal levels induced significant inhibition of intracellular
      calcium mobilization by both alphaCD3 and SDF-1alpha. Cholesterol-loaded
      peripheral T cells were completely unresponsive to alphaCD3/alphaCD28
      stimulation, demonstrating no increase in IL-2, GM1 expression or cell size. T
      cell polarization of lipid rafts to alphaCD3/alphaCD28 beads was also impaired.
      In addition, cholesterol loading potently inhibited SDF-1alpha-induced
      chemotaxis. We propose that excess membrane cholesterol could potentially disrupt
      raft-related cell functions downstream of receptor triggering and that the loss
      of cholesterol regulation of aging immune cells could contribute to immune cell
      senescence.

PMID- 15491684
TI  - Doxycycline-regulated over-expression of hsp22 has negative effects on stress
      resistance and life span in adult Drosophila melanogaster.
AB  - Drosophila hsp22 is a member of the small heat shock proteins family (shsps). The
      hsp22 is expressed in a tissue-general pattern in response to heat stress and
      during normal aging, and localizes to the mitochondrial matrix, however, its
      exact function and targets are unknown. Hsp22 was found to be rapidly induced in
      response to oxidative stress, indicating that hsp22 is also an oxidative stress
      response gene. To assay for effects of hsp22, a ubiquitous pattern of hsp22 gene
      expression was generated in young flies using the "tet-on" doxycycline-regulated
      promoter system. The hsp22 over-expression made flies more sensitive to heat and
      oxidative stress, while resistance to coumarin poisoning was not affected. Life
      span was also reduced, particularly at higher culture temperatures. Members of
      other hsp families have been shown to feedback-inhibit their own expression by
      interacting with the heat shock transcription factor (HSF) and preventing binding
      to the HSEs. Induction of hsp22:lacZ and hsp70:lacZ reporter transgenes in
      response to acute stress was normal in the presence of hsp22 protein over
      expression and in old flies, indicating that the negative effects of hsp22 are
      downstream of the HSF/HSE pathway and the transcriptional heat shock response.
      The data demonstrate a specific over-expression phenotype for hsp22 and suggest
      that hsp22 interacts with heat and oxidative stress resistance pathways.

PMID- 15491685
TI  - Radiotherapy for prostate cancer: brachytherapy alone.

PMID- 15491686
TI  - Summary of simultaneous irradiation for prostate cancer.

PMID- 15491687
TI  - Rationale for use of cyclooxygenase-2 inhibitors in prevention and treatment of
      bladder cancer.

PMID- 15491688
TI  - Results with 7.5F versus 10F rigid ureteroscopes in treatment of ureteral
      calculi.
AB  - OBJECTIVES: To compare the success and complication rates in the treatment of
      ureteral stones with a 7.5F versus a 10F ureteroscope. METHODS: A total of 100
      patients who were scheduled for ureteroscopy to treat ureteral calculi between
      December 2000 and December 2002 were randomly assigned to procedures with a 7.5F
      (group 1; n = 50) or 10F (group 2; n = 50) ureteroscope. The group results were
      compared. RESULTS: Group 1 had 36 distal, 9 middle, and 5 proximal ureteral
      stones. Group 2 had 37 distal, 6 middle, and 7 proximal ureteral stones. No
      statistically significant differences were noted between the two groups with
      respect to the mean stone size or operation time (P = 0.175 and P = 0.636,
      respectively). Pneumatic lithotripsy was used in 62% and 50% of the procedures in
      group 1 and 2, respectively, and stones or fragments were retrieved with basket
      catheters in 92% and 76% of the group procedures, respectively. The difference
      between the group rates for successful basket catheter extraction was
      statistically significant (P = 0.029). Of the patients in group 1 and 2, 84% and
      80%, respectively, were stone free after a single procedure (P = 0.603). The
      corresponding failure rates in the two groups were 6% and 12% (P = 0.295), and
      the corresponding early and late complication rates in the two groups were 6% and
      4% (P = 0.646). None of the patients in group 1 developed late complications. One
      individual (2%) in group 2 developed ureteral stenosis during long-term follow-up
      (P = 0.315). CONCLUSIONS: The success and failure rates revealed better outcomes
      for treatment of ureteral calculi with a 7.5F ureteroscope, but the differences
      were not statistically significant. The complication rates were similar between
      the two groups. Basket catheters were used more frequently with the 7.5F scope,
      and the rates of in situ lithotripsy and postoperative ureteral stent placement
      were also greater in patients treated with this instrument.

PMID- 15491691
TI  - Long-term outcome of ventral buccal mucosa onlay graft urethroplasty for urethral
      stricture repair.
AB  - OBJECTIVES: To evaluate our patients who were treated with ventral buccal mucosa
      onlay grafts for open urethral stricture repair with a follow-up exceeding 5
      years. Buccal mucosa onlay is widely used for urethral reconstruction; however,
      the long-term outcome of these patients remains unclear. METHODS: During the past
      10 years, 67 patients underwent ventral buccal mucosa onlay graft surgery for
      urethral stricture repair. Of these, 32 were followed up for longer than 5 years
      (mean 6.9 years) for the occurrence and timing of any postoperative
      complications. All patients had undergone prior internal urethrotomy (mean 2.9
      procedures), and the average length of the stricture was 4.3 cm (range 3 to 17).
      RESULTS: The overall complication rate was 25% (8 of 32). We observed one
      fistula, one graft infection/necrosis, two lower lip scars with transient
      impairment of lip motility, and four recurrent strictures (at the proximal
      anastomosis), all of which were treated successfully with internal urethrotomy.
      All but one recurrent stricture occurred during the first 12 postoperative
      months. CONCLUSIONS: Ventral buccal mucosa onlay grafting for urethral stricture
      repair provides stable long-term results with complications occurring primarily
      during the first 12 postoperative months.

PMID- 15491692
TI  - Refinements in treatment of large bladder calculi: simultaneous percutaneous
      suprapubic and transurethral cystolithotripsy.
AB  - OBJECTIVES: To present a combined endourologic approach to treat bladder calculi
      consisting of simultaneous percutaneous suprapubic and transurethral
      cystolithotripsy. METHODS: We report on a series of 12 consecutive patients with
      bladder stone burdens of 40 mm or greater. Percutaneous 30F access was obtained
      under cystoscopic control. Fragmentation and stone removal were performed
      simultaneously by two urologists using a Swiss lithoclast, holmium laser, and/or
      ultrasound lithotriptor through both percutaneous and transurethral routes.
      Suprapubic and transurethral catheters were placed postoperatively. RESULTS:
      Twelve patients with a median age of 66 years (range 33 to 80) were treated by
      simultaneous percutaneous suprapubic and transurethral cystolithotripsy. Six
      underwent transurethral resection of the prostate at the completion of stone
      clearance. The median stone size was 60 mm (range 40 to 80), and the median
      lithotripsy time was 56 minutes (range 45 to 70). The median postoperative
      hospitalization was 2.7 days (range 2 to 5), and complete stone clearance was
      achieved in all cases. One patient, who underwent concomitant transurethral
      resection of the prostate, developed urinary retention 1 week postoperatively and
      was successfully treated by temporary transurethral catheterization. One patient
      with a positive urine culture preoperatively developed fever on the first
      postoperative day and was treated with intravenous antibiotics according to the
      antibiogram results for 5 days. No other complications had occurred after a
      median follow-up of 10 months (range 3 to 15). CONCLUSIONS: Simultaneous
      percutaneous suprapubic and transurethral cystolithotripsy appears to be a safe
      approach for the management of large bladder calculi and may shorten the total
      fragmentation time. It can be combined with transurethral resection of the
      prostate without prolonging hospitalization. The simultaneous use of two
      modalities of stone fragmentation represents an effective and minimally invasive
      way of treating large bladder calculi.

PMID- 15491693
TI  - En bloc stapling of renal hilum during laparoscopic nephrectomy and
      nephroureterectomy.
AB  - OBJECTIVES: To evaluate the safety and advisability of en bloc mass stapling of
      the renal pedicle during difficult laparoscopic nephrectomy to avoid conversion
      to an open procedure. METHODS: A retrospective chart review was performed of 433
      consecutive patients undergoing laparoscopic simple or radical nephrectomy or
      laparoscopic nephroureterectomy between August 1998 and July 2003 by two
      surgeons. In all cases of en bloc hilar ligation, a stapler was deployed across
      the renal hilum without individual dissection of the renal artery and vein.
      RESULTS: The overall incidence of en bloc ligation was 6.0% (26 of 433 patients).
      The reasons for en bloc ligation were a difficult hilar dissection and/or the
      appearance of the renal hilum in 21 cases and urgent ligation secondary to
      bleeding in 5 cases. No correlation was found between surgeon experience and the
      frequency of en bloc ligation. No immediate or short-term complications related
      to this method of hilar division were observed with a mean follow-up of 26
      months. CONCLUSIONS: In this study, no cases of arteriovenous fistula development
      occurred after en bloc stapling of the renal pedicle. Long-term follow-up is
      needed, because arteriovenous fistula development may be a late complication of
      nephrectomy. Although we do not advocate the generalized use of en bloc division
      of the renal pedicle, early data suggest that en bloc stapling can be performed
      to avoid conversion to an open procedure with no related short-term
      complications.

PMID- 15491694
TI  - Acute histologic effects of temperature-based radiofrequency ablation on renal
      tumor pathologic interpretation.
AB  - OBJECTIVES: To describe the histopathologic changes and evaluate the
      interpretability of human renal tumor specimens obtained after temperature-based
      radiofrequency ablation (RFA). METHODS: RFA of 119 solid kidney tumors was
      performed percutaneously under computed tomography guidance, laparoscopically or
      during open surgery, using a temperature-based system. Of the 119 tumors, 70 were
      biopsied (two or more samples) after RFA, 39 immediately before ablation, and 10
      were not biopsied. All specimens were pathologically classified, and for those
      specimens obtained after RFA, analysis of the acute histologic changes secondary
      to RFA was performed by a single pathologist using standard hematoxylin-eosin
      staining. RESULTS: Ablated tumor specimens maintained their tissue architecture
      and had predictable changes (cytoplasmic eosinophilia, nuclear elongation,
      cytoplasmic dissolution) easily recognizable by our pathologists. The diagnostic
      rate of renal cell carcinoma after RFA (72%) was comparable to the diagnostic
      rate reported for tumors less than 4 cm in other non-RFA biopsy series. Only 2.6%
      of specimens obtained before and 5.7% obtained after RFA were nondiagnostic
      secondary to the paucity of tissue obtained. In 8.3% of all tumors (regardless of
      RFA treatment), the distinction between oncocytoma and low-grade oncocytic renal
      cell carcinoma could not be made because of insufficient tissue. CONCLUSIONS:
      Acutely, RFA of renal tumors causes predictable histologic changes and preserves
      the tissue architecture. Obtaining two or more incisional biopsies after RFA
      provided sufficient tissue for reliable pathologic diagnosis.

PMID- 15491695
TI  - Recoverability of renal function after treatment of adult patients with
      unilateral obstructive uropathy and normal contralateral kidney: a prospective
      study.
AB  - OBJECTIVES: To study the methods of prediction of recoverability of renal
      function after the treatment of adult patients with unilateral obstructive
      uropathy and a normal contralateral kidney. METHODS: This prospective study
      included 91 consecutive adult patients with the diagnosis of unilateral
      obstructive uropathy and a normal contralateral kidney. All patients had a
      nonequivocal cause of obstruction that was successfully relieved after treatment.
      All patients underwent plain abdominal x-ray, gray-scale ultrasonography, Doppler
      ultrasonography, excretory urography, and technetium-99m-diethylenetriamine
      pentaacetic acid radioisotope renography before and after treatment. Patients
      were seen regularly at 3, 6, and 12 months for a mean duration of 13 +/- 6 months
      (range 6 to 36). At each visit, ultrasonography and renography were performed,
      and excretory urography was performed at least once during follow-up. Several
      renographic and ultrasound parameters were studied before and after treatment to
      evaluate their value in predicting the recoverability of renal function. The
      difference between the selective renographic glomerular filtration rate (GFR) of
      the ipsilateral kidney before treatment and its mean value after treatment was
      considered as the reference variable to which all other variables were compared.
      All prognostic parameters were evaluated by both univariate and multivariate
      analyses. RESULTS: On univariate analysis, the factors that significantly
      affected the recoverability of renal function after the relief of obstruction
      included preoperative renographic GFR, renal perfusion, parenchymal thickness,
      parenchymal echogenicity, corticomedullary differentiation, reduction of the
      renal resistive index of the corresponding kidney, and compensatory hypertrophy
      of the contralateral normal kidney. However, using multivariate analysis, only
      the preoperative selective renographic GFR and renal perfusion of the
      corresponding kidney sustained their statistical significance as independent
      factors affecting renal functional recovery. A preoperative GFR value of 10
      mL/min/1.73 m2 was estimated as the cutoff point that can determine the best
      prediction of stabilization or improvement of renal function after the relief of
      obstruction. CONCLUSIONS: Preoperative renographic clearance and perfusion of the
      corresponding kidney were the only predictors of recoverability of unilateral
      renal obstruction. Kidneys with a renographic GFR of less than 10 mL/min/1.73 m2
      were irreversibly damaged. Improvement or stabilization of function can be
      expected after relief of obstruction of kidneys with a renographic GFR of 10
      mL/min/1.73 m2 or greater.

PMID- 15491696
TI  - Osseous complications after transvaginal bone anchor fixation in female pelvic
      reconstructive surgery: report from single largest prospective series and
      literature review.
AB  - OBJECTIVES: To report, from our prospective database and review of published
      studies (including primary reported patient series and case reports for osseous
      complications after transvaginal bone anchor fixation in female pelvic
      reconstructive surgery), our results and those from previously reported patient
      series to determine the incidence of osteitis pubis and osteomyelitis. METHODS: A
      total of 440 patients from our database of cadaveric transvaginal sling (n = 127)
      and cadaveric prolapse repair with sling (n = 313) procedures had at least 3
      months of examination follow-up and were included in this report. We found 15
      primary reported patient series involving transvaginal bone anchor fixation in
      published studies, for a total of 788 patients. The combined patient population
      of 1228 was assessed for the incidence of osteitis pubis and osteomyelitis.
      RESULTS: Of our 440 patients included in this study, 2 developed osteitis pubis
      (0.45%), and none had osteomyelitis (0%). In the published studies we reviewed,
      no case of osteitis pubis and 1 case of osteomyelitis (1 of 788, 0.13%) were
      reported. One additional case of osteomyelitis with transvaginal bone anchor
      fixation was reported. The combined incidence of osteitis pubis was 2 (0.16%) of
      1228, and the combined incidence of osteomyelitis was 1 (0.08%) of 1228.
      CONCLUSIONS: In procedures using transvaginal bone anchor fixation in female
      pelvic reconstructive surgery, the combined incidence, from our experience and
      that reported in published studies, of osteitis pubis and osteomyelitis was 2
      (0.16%) and 1 (0.08%) of 1228, respectively. The infectious osseous complication
      rate associated with transvaginal pubic bone anchor fixation appears to be less
      than that previously reported for suprapubic bone anchor placement. In our
      experience, when using careful surgical technique and proper prophylactic
      precautions, infectious osseous complications have not been encountered.

PMID- 15491697
TI  - Refining diagnosis of anatomic female bladder outlet obstruction: comparison of
      pressure-flow study parameters in clinically obstructed women with those of
      normal controls.
AB  - OBJECTIVES: To improve the definition of pressure-flow study cutoff values for
      anatomic female bladder outlet obstruction (BOO) by comparing these parameters in
      women with clinical obstruction with those of normal controls. METHODS: In the
      past 3 years, 82 consecutive women with clinical anatomic BOO were investigated
      according to an institutional review board-approved protocol that included
      imaging and urodynamic studies. The data from these women were then added to
      those of our previously published cohort of 87 patients. The controls were 20
      female volunteers without any urologic complaints and without a history of
      bladder or urethral surgery who had undergone a urodynamic study. Three groups of
      women with BOO were identified in the most recent cohort: 20 with Stage III-IV
      cystocele, 23 who had undergone previous anti-incontinence surgery, and 39 with
      distal periurethral fibrosis or stricture. The optimal combination of the maximal
      flow rate (Qmax) and detrusor pressure at maximal flow rate (PdetQmax) for
      determining BOO was calculated using nonparametric receiver operating
      characteristic curves for the entire cohort of 169 women with obstruction.
      RESULTS: Age, Qmax, and PdetQmax were similar among the three BOO groups. The
      area under the receiver operating characteristic curve for BOO was 0.762 for Qmax
      (95% confidence interval 0.661 to 0.864, P <0.001) and 0.721 for PdetQmax (95%
      confidence interval 0.617 to 0.824, P <0.001). After adjusting for the effect of
      age, PdetQmax (P <0.001) and Qmax (P <0.011) were independently associated with
      BOO. CONCLUSIONS: After adjusting for age and using normal controls rather than
      an incontinent control population, we present pressure-flow study cutoff values
      to aid in the urodynamic study diagnosis of women with anatomic BOO.

PMID- 15491700
TI  - Sexual function after male radical cystectomy in a sexually active population.
AB  - OBJECTIVES: To assess sexual dysfunction in sexually active men after radical
      cystectomy (RC) and to determine whether sildenafil citrate can improve erectile
      dysfunction after surgery. METHODS: The baseline and follow-up data from 49
      sexually active male patients (mean age 57.8 +/- 9.1 years) undergoing RC (1995
      to 2002) were obtained. Of the 49 patients, 16 (33%) had undergone nerve-sparing
      RC; 38 (78%) had undergone orthotopic diversion; 8 (16%) had undergone ileal
      conduit diversion; and 3 (6%) had undergone cutaneous continent diversion. The
      data were assessed using the abridged 5-item International Index of Erectile
      Function questionnaire, referred to as the Sexual Health Inventory for Men
      (SHIM). RESULTS: At a mean follow-up of 47.6 +/- 22.7 months, the total mean SHIM
      score decreased from 22.08 +/- 3.96 to 4.33 +/- 5.72 after RC (P <0.05). Of the
      49 patients, 42 (86%) did not have erections sufficient for vaginal penetration.
      Of these 42 patients, 22 (52%) tried sildenafil citrate. Of these 22 patients,
      only 2 (9%) responded positively, with a total mean SHIM score of 23.50 +/- 2.12.
      Although the mean SHIM score after orthotopic substitution (5.24 +/- 6.21) was
      statistically significant compared with that after ileal conduit (1.13 +/- 0.33)
      and cutaneous continent (1.33 +/- 0.58) diversions, this was not clinically
      significant. CONCLUSIONS: Male erectile dysfunction after RC is a prevalent
      problem. In our series, only 9 (14%) of 49 sexually active men were potent after
      surgery. Of these 9 potent patients, 8 (89%) had undergone nerve-sparing RC. Of
      concern, only 52% of the patients with erectile dysfunction sought treatment
      after RC.

PMID- 15491702
TI  - Evaluation of nuclear matrix protein-22 as a clinical diagnostic marker for
      bladder cancer.
AB  - OBJECTIVES: To evaluate prospectively the prognostic power of urinary nuclear
      matrix protein-22 (NMP-22) for bladder cancer in Taiwanese screening and
      surveillance settings. METHODS: Single voided urine samples were obtained from 68
      healthy individuals, 303 patients with benign urothelial diseases, and 28
      patients with urogenital tumors. The NMP-22 levels in the urine samples were
      measured using enzyme-linked immunosorbent assay methods. RESULTS: The median NMP
      22 level in healthy individuals and patients with benign and malignant disease
      was 5.9, 4.8, and 7.4 U/mL, respectively. The positive NMP-22 rate in healthy
      individuals and patients with benign and malignant disease was 4.4%, 17.2%, and
      50%, respectively. The sensitivity, specificity, positive predictive value, and
      negative predictive value was 50%, 82.8%, 21.2%, and 94.7%, respectively, using
      7.5 U/mL as the cutoff value. CONCLUSIONS: Our data demonstrated that NMP-22 is
      not a good diagnostic tool for screening or follow-up surveillance of bladder
      cancer owing to its low sensitivity and positive predictive value. Nevertheless,
      it could be adopted as a tool to rule out the possibility or risk of developing
      bladder cancer because of its high negative predictive value in our study.

PMID- 15491703
TI  - Volumetric density of elastic and reticular fibers in transition zone of controls
      and patients with benign prostatic hyperplasia.
AB  - OBJECTIVES: To analyze the volumetric density (Vv) of elastic and reticular
      fibers in the transition zone of controls and patients with benign prostatic
      hyperplasia (BPH). METHODS: Prostatic tissue samples were obtained from 25
      patients (age range 63 to 79 years, mean 68) with clinical symptoms of bladder
      outlet obstruction who had undergone open prostatectomy. The control group was
      composed of 25 transition zone samples from prostates obtained during autopsy of
      adults aged younger than 30 years (killed in accidents). The Vv of the elastic
      and reticular fibers was determined in 25 random fields per prostate, using the
      point-count method with an M-42 grid test system. The data were analyzed using
      the Kolmogorov-Smirnov, Shapiro-Wilk W, and Mann-Whitney U tests. The Vv of these
      components was determined by stereologic methods. RESULTS: The Vv in the control
      and BPH groups was 12.47% +/- 3.6% and 16.55% +/- 9.11% in the elastic system
      fibers (difference not statistically significant) and 22.75% +/- 1.66% and 29.33%
      +/- 1.08% in the reticular fibers (difference statistically significant),
      respectively. CONCLUSIONS: Reticular fibers showed a statistically significant
      increase in the BPH samples, and this finding suggests that stromal network
      fibers play a significant role in BPH.

PMID- 15491704
TI  - Three-year follow-up of feedback microwave thermotherapy versus TURP for clinical
      BPH: a prospective randomized multicenter study.
AB  - OBJECTIVES: To compare, in a prospective randomized multicenter study, the
      efficacy and safety of transurethral microwave thermotherapy with ProstaLund
      Feedback Treatment (PLFT), using the CoreTherm device, with transurethral
      resection of the prostate (TURP) 36 months after treatment. METHODS: The study
      was conducted at 10 centers in the United States and Scandinavia. A total of 154
      patients with benign prostatic hyperplasia were randomized to PLFT or TURP in a
      2:1 ratio. The treatment outcome was evaluated on the basis of the International
      Prostate Symptom Score (IPSS), the quality-of-life question (QOL) of the IPSS,
      peak urinary flow rate (Qmax), urodynamics, and adverse events. The microwave
      power and treatment time were adjusted according to each patient's response to
      the supplied energy (ie, the intraprostatic temperature guided the PLFT).
      RESULTS: Statistically significant improvements in both the TURP and the PLFT
      groups were observed for IPSS, QOL, and Qmax at 36 months. The average value for
      the PLFT group was 8.2, 1.2, and 11.9 mL/s for IPSS, QOL, and Qmax, respectively.
      The corresponding values for the TURP group were IPSS 5.0, QOL 1.0, and Qmax 13.5
      mL/s. The difference in IPSS outcome was statistically significant; however, no
      statistically significant differences were found in QOL or Qmax between the two
      treatment groups. The degree of improvement was in the same range as that
      observed after 12 and 24 months for both groups. During the 12 to 36-month
      period, the most frequent adverse events in the TURP group were impotence (15%),
      micturition urgency (13%), and urethral disorder (8%); in the PLFT group,
      impotence (8%), prostate-specific antigen increase (5%), and hematuria (4%) were
      the most common. CONCLUSIONS: The clinical outcome 3 years after microwave
      thermotherapy with PLFT was comparable to the results seen after TURP. The safety
      of PLFT compared favorably to that of TURP in this study.

PMID- 15491705
TI  - Efficacy of high-energy transurethral microwave thermotherapy in alleviating
      medically refractory urinary retention due to benign prostatic hyperplasia.
AB  - OBJECTIVES: To determine the efficacy of high-energy transurethral microwave
      thermotherapy (HE-TUMT) in treating patients with medically refractory complete
      urinary retention secondary to benign prostatic hyperplasia (BPH). METHODS:
      Between April 2000 and July 2003, 39 patients in urinary retention due to BPH
      were treated with HE-TUMT. A Foley catheter was reinserted after HE-TUMT and
      removed at 3 weeks for a voiding trial. Patients unable to void were
      recatheterized, and voiding trials were repeated at 2-week intervals. Patients
      were evaluated according to history and physical examination, prostate-specific
      antigen level, prostate volume, cystourethroscopy, International Prostate Symptom
      Score, quality of life score, peak uroflow, and postvoid residual. Success was
      defined as the ability to urinate after HE-TUMT without the need for further
      intervention. RESULTS: The mean (+/- SD) patient age was 72 +/- 9.3 years. Mean
      follow-up period was 18 +/- 10.2 months. Twenty patients (51%) were characterized
      as American Society of Anesthesiologists class III or higher. The mean prostate
      volume was 75.2 +/- 57.6 cm3. The mean length of time that patients were
      dependent on indwelling Foley catheters before HE-TUMT was 9.6 +/- 14.2 weeks.
      Thirty-two patients were able to void after HE-TUMT, for an overall success rate
      of 82%. Patients voiding successfully after HE-TUMT had a mean of 1.6 +/- 0.8
      voiding trials and required catheters after HE-TUMT for a mean period of 4.1 +/-
      2 weeks. Only 6 (15%) of the patients who were voiding were able to stop their
      medication for BPH. CONCLUSIONS: We found an encouraging success rate with HE
      TUMT in relieving urinary retention in patients with BPH, including those with
      large prostate volumes. It is an acceptable option for patients who are
      considered high risk for surgery. Several patients required multiple voiding
      trials before spontaneous urination, which suggests that improvements in bladder
      outlet obstruction might require a prolonged period after HE-TUMT. Finally, many
      patients might require continued use of medications after HE-TUMT.

PMID- 15491706
TI  - Phytoestrogen tissue levels in benign prostatic hyperplasia and prostate cancer
      and their association with prostatic diseases.
AB  - OBJECTIVES: To compare phytoestrogen tissue levels in men with small-volume
      benign prostatic hyperplasia (BPH), large-volume BPH, and prostate cancer (PCa).
      METHODS: Prostatic tissue samples of men consuming a Western diet who underwent
      surgery for BPH (n = 63) or PCa (n = 31) were collected and frozen at -40 degrees
      C. In the tissue samples, the enterolactone and genistein levels were determined
      in duplicate by monoclonal antibody-based immunoassays. We subsequently compared
      the tissue levels in patients with BPH and PCa and studied the impact of
      enterolactone and genistein on prostate volume. RESULTS: The enterolactone tissue
      levels were comparable in patients with BPH and PCa and revealed no correlation
      to prostate volume. The genistein tissue levels tended to be lower in patients
      with PCa (median 8.4 ng/g dry weight) compared with the entire BPH group (11.0
      ng/g dry weight; P = 0.072). In addition, the genistein tissue levels were
      significantly greater in men with small-volume BPH (median 20.9 ng/g dry weight)
      compared with those with large-volume BPH (8.8 ng/g dry weight; P = 0.023).
      CONCLUSIONS: Our data suggest an involvement of genistein in the pathogenesis of
      BPH and, possibly, of PCa. The impact of enterolactone is currently unknown.

PMID- 15491707
TI  - Delayed intraoperative hydration limits blood loss during radical retropubic
      prostatectomy.
AB  - OBJECTIVES: To evaluate the effects of limiting hydration during prostate
      mobilization on intraoperative blood loss. METHODS: The patient records of 519
      consecutive men undergoing radical retropubic prostatectomy by a single surgeon
      from January 2000 through April 2003 were reviewed. In the initial 328 cases,
      intravenous fluids were not limited throughout the case (constant hydration
      group). In the next 189 cases, intravenous fluids were limited to a target of
      1500 mL during prostate dissection (delayed hydration group). After the prostate
      was removed, hydration was brisk for an additional target of 3500 mL. The patient
      characteristics, perioperative events, and postoperative recovery were evaluated.
      RESULTS: Delayed hydration resulted in a statistically significant reduction in
      estimated blood loss compared with the constant hydration group, averaging 700 mL
      versus 965 mL, respectively. The immediate postoperative hematocrit values were
      also significantly greater in the delayed hydration group (31.5%) than in the
      constant hydration group (30.2%). Furthermore, the delayed hydration group had
      significantly fewer cases of blood loss greater than 1500 mL and fewer patients
      needed intraoperative transfusions. No statistically significant difference was
      found in total intravenous fluids given and no increased morbidity occurred with
      delayed hydration. CONCLUSIONS: Delayed hydration appears to reduce blood loss
      during radical retropubic prostatectomy. In the hemodynamically stable patient,
      limiting intravenous fluids before complete dissection of the prostate is
      feasible without increasing morbidity.

PMID- 15491708
TI  - Alcohol and the risk of prostate cancer and benign prostatic hyperplasia.
AB  - OBJECTIVES: To examine the association between alcohol and the risk of prostate
      cancer/benign prostatic hyperplasia (BPH) in a population with a wide range of
      alcohol consumption, using a hospital-based, case-control study. Data from
      several epidemiologic studies have allowed us to exclude a strong association
      between alcohol drinking and prostate cancer risk. However, limited information
      is available for BPH. Also, it is unclear whether various types of alcoholic
      beverages may have a different impact on risk. METHODS: We conducted this
      hospital-based case-control study in Italy between 1991 and 2002. A total of 2663
      men younger than 75 years had incident, histologically confirmed prostate
      carcinoma (1294 cases) or symptomatic obstructive BPH (1369 cases) (maximal flow
      rate less than 15 mL/s) refractory to medical treatment. A total of 1451 patients
      younger than 75 years were used as controls. Odds ratios and corresponding 95%
      confidence intervals were estimated using unconditional multiple logistic
      regression models including terms for age, center, education, body mass index,
      physical activity, and family history of prostate cancer. RESULTS: Alcohol
      consumption showed no consistent association with prostate cancer risk, but a
      statistically significant inverse trend in risk for BPH. Compared with
      abstainers, the odds ratio was 0.88 for fewer than three drinks, 0.71 for three
      to four drinks, 0.79 for five to six drinks, and 0.65 for seven or more drinks
      per day. The patterns of risk were similar with reference to different alcoholic
      beverages. The inverse relation between elevated alcohol consumption and BPH was
      apparently stronger in subjects with a lower body mass index. CONCLUSIONS:
      Alcohol drinking is unrelated to prostate cancer risk. The inverse relationship
      with BPH may be related to the hormonal correlates (ie, lower androgen levels) of
      heavy alcohol drinkers.

PMID- 15491709
TI  - Preoperative PSA level significantly associated with interval to biochemical
      progression after radical retropubic prostatectomy.
AB  - OBJECTIVES: To evaluate the association between the preoperative prostate
      specific antigen (PSA) level and the interval to biochemical progression after
      radical retropubic prostatectomy (RRP) for prostate cancer. METHODS: We studied
      5534 men who underwent RRP for prostate cancer during a 15-year period and were
      enrolled in prospective follow-up studies. Of these men, 857 (15%) subsequently
      had biochemical evidence of cancer progression (PSA greater than 0.2 ng/mL). All
      men with biochemical progression after RRP were arbitrarily stratified into five
      groups according to their preoperative PSA level: less than 2.6 ng/mL, 2.6 to 4
      ng/mL, 4.1 to 10 ng/mL, 10.1 to 20 ng/mL, and greater than 20 ng/mL. The time to
      biochemical progression after RRP was the primary endpoint of the analysis. Other
      prognostic factors were also evaluated in multivariable analysis. RESULTS: The
      median time to progression for men with a PSA level greater than 20 ng/mL was
      significantly shorter (16 months) than for men with a PSA level of 10.1 to 20
      ng/mL (27 months) or those with lower PSA levels (P = 0.0005). Men with a PSA
      level of 4.1 to 10 ng/mL did not have a statistically significantly different
      median time to progression (31 months) from men with a PSA level of 10.1 to 20
      ng/mL (27 months; P = 0.3), 2.6 to 4 ng/mL (32 months; P = 0.8), or less than 2.6
      ng/mL (38 months; P = 0.3). Also, no statistically significant difference was
      found in the median time to progression between men with a PSA level of 2.6 to 4
      ng/mL and less than 2.6 ng/mL (P = 0.4). In an analysis of covariance
      multivariate analysis, the preoperative PSA level was not an independent
      predictor of the time to biochemical progression (P = 0.12), after accounting for
      tumor stage and Gleason grade. CONCLUSIONS: The preoperative PSA level was
      significantly associated with the interval to biochemical cancer progression
      after RRP; however, this association appeared to be because the preoperative PSA
      level serves as a surrogate marker for other prognostic factors, such as the
      tumor volume, tumor stage, and Gleason grade.

PMID- 15491710
TI  - Influence of patient age on biochemical freedom from disease in patients
      undergoing conformal proton radiotherapy of organ-confined prostate cancer.
AB  - OBJECTIVES: To examine a large, single-institution series of patients to test the
      perception among clinicians that radiotherapy is preferred for "older" patients
      and surgery should be indicated for "younger" men. Both radiotherapy and surgery
      are used to control prostate cancer, and both yield similar results in terms of
      long-term biochemical disease-free (bNED) survival. METHODS: The bNED survival
      results from more than 1000 patients treated solely with conformal radiotherapy
      were analyzed to determine whether a difference in outcome supervened for
      patients younger than 60 years of age versus older patients. RESULTS: No
      statistically significant difference in bNED survival was found, in terms of
      patient age. Statistically significant predictors of outcome included
      pretreatment prostate-specific antigen level, clinical stage at diagnosis, and
      Gleason score. CONCLUSIONS: Patient age younger than 60 years versus older than
      60 years at treatment did not influence bNED survival significantly. Patient age
      at treatment should not be used in and of itself to recommend one type of
      treatment over another.

PMID- 15491711
TI  - Characterization of minute adenocarcinomas of prostate at radical prostatectomy.
AB  - OBJECTIVES: To characterize minute prostate cancer seen at radical prostatectomy.
      With aggressive screening and more extensive biopsy sampling, we have
      increasingly seen these cancers at radical prostatectomy. METHODS: We examined
      radical prostatectomy specimens submitted in total for minute cancer. RESULTS:
      During the past 1.5 years, 78 prostates (5.2%) had either no cancer (2 cases) or
      contained between one and six foci of organ-confined carcinoma (76 cases)
      measuring 6 mm or less, with a Gleason score of 6 or less. The mean prebiopsy
      serum prostate-specific antigen level was 5.8 ng/mL, and 84.6% of the patients
      had undergone biopsy because of an elevated prostate-specific antigen level. Of
      these patients, 40% had had either benign or atypical diagnoses on prior
      biopsies, and 43% had only minute (0.5 mm or less) foci of carcinoma on biopsy.
      The radical prostatectomy specimens had a mean of two cancer foci measuring, on
      average, 3 mm in the greatest dimension. In 85% of the cases, the side of the
      positive biopsy matched the side of the carcinoma found at radical prostatectomy;
      81.5% of cases had high-grade prostatic intraepithelial neoplasia immediately
      adjacent to the cancer. CONCLUSIONS: The incidence of minute carcinoma of the
      prostate has increased from 0.5% in 1988 to 5.2% in the current study. The
      patients often had moderately increased prostate-specific antigen levels and
      minute foci of carcinoma on biopsy. These small tumors at radical prostatectomy
      are usually discovered by fortuitous biopsy that is often preceded by other
      biopsies with noncancerous diagnoses. Patients with the above clinical and biopsy
      findings should be counseled about the possibility of finding only minute foci of
      carcinoma at radical prostatectomy and may want to consider watchful waiting.

PMID- 15491712
TI  - Racial disparity in clinical course and outcome of metastatic androgen
      independent prostate cancer.
AB  - OBJECTIVES: To perform a review of patient and disease characteristics and
      response and survival outcomes of patients with metastatic androgen-independent
      prostate cancer. Racial differences in prostate cancer have usually been
      attributed to socioeconomic status, quality of care, comorbidities, and dietary
      factors. In a clinical trial population, some of these factors, such as access to
      care and performance status, are likely to be relatively uniform. METHODS: The
      patients included in the review had been registered in clinical trials between
      1991 and 2001 at Wayne State University. RESULTS: Of 145 patients, 90 (62%) were
      white Americans and 55 (38%) were black Americans, 27% were 70 years or older,
      and 34% had minimal metastatic disease (axial bony involvement and/or lymph node
      involvement) and 66% had extensive disease (appendicular skeleton and/or visceral
      involvement). The chi-square test demonstrated no statistically significant
      difference by race in the distribution of the patient and disease
      characteristics. The prostate-specific antigen response rate was 41% in whites
      and 29% in blacks (P = 0.12). Log-rank analysis revealed race to be the only
      statistically significant factor predictive of the time to prostate-specific
      antigen progression (P = 0.02, median 4.6 months in whites and 2.3 months in
      blacks). No statistically significant difference by race was found in overall
      survival. Poor performance status, extensive disease, elevated alkaline
      phosphatase and lactate dehydrogenase levels, and a lack of prostate-specific
      antigen response were statistically significant predictors of worse overall
      survival. CONCLUSIONS: In patients with androgen-independent metastatic prostate
      cancer studied in clinical trials, race was an independent predictor of
      therapeutic outcome. Additional investigation of the biologic and genetic
      differences underlying this clinical disparity is warranted.

PMID- 15491713
TI  - Local recurrence after radical cystectomy for invasive bladder cancer: an
      analysis of predictive factors.
AB  - OBJECTIVES: To examine which clinicopathologic parameters predict clinically
      detectable local recurrence after radical cystectomy. Local recurrence after
      radical cystectomy for invasive bladder cancer was infrequently observed until 20
      years ago because of the lack of adequate diagnostic tools. The recent
      development and use of pelvic computed tomography has allowed us to detect local
      recurrence more precisely. However, only a few studies have investigated the rate
      and pattern of local recurrence in the computed tomography era. METHODS: This
      retrospective review included 145 patients with muscle-invasive bladder cancer
      treated with radical cystectomy, regional pelvic lymph node dissection, and
      urinary diversion between January 1990 and December 2001. The development of
      local recurrence and/or distant metastasis was analyzed as the endpoint using
      univariate and multivariate analyses. RESULTS: Local recurrence developed in 27
      (18.6%) of the 145 patients at a median of 8 months after cystectomy. Of the 27
      patients, 8 had local recurrence alone and 19 had concurrent distant metastasis.
      Distant metastasis without local recurrence developed in 34 patients (23.4%).
      Univariate and multivariate analyses revealed that Stage pT3-T4 and pathologic
      pelvic lymph node involvement were statistically significant factors predicting
      clinical failure, local recurrence, and/or distant metastasis. However, a
      concomitant squamous cell carcinoma component in the specimen was the only
      independent predictor of local recurrence alone in both univariate and
      multivariate analyses. CONCLUSIONS: Only the finding of a concomitant squamous
      cell carcinoma component in the specimen was an independent predictor of local
      recurrence in patients treated with radical cystectomy.

PMID- 15491714
TI  - Vascular invasion predicts recurrence after radical prostatectomy: stratification
      of risk based on pathologic variables.
AB  - OBJECTIVES: To determine whether vascular invasion (VI) is an independent
      predictor of prostate cancer recurrence and/or survival and to stratify risk of
      recurrence in patients with VI. METHODS: Vascular invasion status was documented
      in 620 radical prostatectomy specimens with an average of 7.5 years of follow-up.
      The relationship between VI and other clinical and pathologic features was
      tested. Vascular invasion as an independent predictor of recurrence was
      investigated by logistic regression analysis. Survival analyses and
      stratification of VI patients was developed with Kaplan-Meier survival curves.
      RESULTS: Vascular invasion was identified in 110 patients (18%) and correlated
      significantly (P <0.0001) with high Gleason grade, extracapsular extension (EPE),
      seminal vesicle invasion, increasing cancer volumes, positive margins, and
      elevated preoperative prostate-specific antigen (PSA) levels. Logistic regression
      analysis demonstrated that VI was a strong and independent predictor for disease
      recurrence, when considered with grade, EPE, seminal vesicle invasion, lymph node
      involvement, cancer volume, preoperative PSA levels, and positive margins. At 12
      years after radical prostatectomy, patients with VI demonstrated significantly
      lower disease-specific survival (P = 0.0005). Among patients with VI,
      stratification of grade, EPE, and the number of VI foci identified three
      significantly different prognostic groups. CONCLUSIONS: In long-term follow-up,
      VI was a significant predictor of prostate cancer recurrence and death after
      radical prostatectomy. In patients with VI, high Gleason grade, EPE, and more
      than five foci of VI are associated with poor prognosis.

PMID- 15491715
TI  - Permanent interstitial brachytherapy in younger patients with clinically organ
      confined prostate cancer.
AB  - OBJECTIVES: To evaluate biochemical progression-free survival in hormone-naive
      men 62 years of age or younger with clinically organ-confined prostate cancer who
      underwent brachytherapy with or without supplemental external beam radiotherapy.
      METHODS: From April 1995 through December 2000, 119 hormone-naive patients 62
      years of age or younger underwent permanent interstitial brachytherapy for
      clinical T1b-T2cNxM0 (2002 American Joint Committee on Cancer) prostate cancer.
      No patient underwent seminal vesicle biopsy or pathologic lymph node staging. The
      median follow-up was 5.4 years. Biochemical progression-free survival was defined
      by either a prostate-specific antigen (PSA) level of 0.4 ng/mL or less after a
      nadir or by the American Society for Therapeutic Radiology and Oncology consensus
      definition. No patient was lost to follow-up. The clinical, treatment, and
      dosimetric parameters evaluated for biochemical progression-free survival
      included age, clinical T stage, Gleason score, pretreatment PSA level, risk
      group, percentage of positive biopsies, isotope, supplemental external beam
      radiotherapy, prostate volume, brachytherapy planning volume, percentage of the
      target volume receiving 100%, 150%, and 200% of the prescribed dose, minimal
      percentage of the prescribed dose covering 90% of the target volume, and tobacco
      status. RESULTS: For the entire group, the actuarial 7-year biochemical
      progression-free survival rate was 96.1% and 98.3% for a PSA cutpoint of 0.4
      ng/mL or less and for the American Society for Therapeutic Radiology and Oncology
      consensus definition, respectively. Using a PSA biochemical control definition of
      0.4 ng/mL or less, 93.1%, 100%, and 95.2% of the low-risk, intermediate-risk, and
      high-risk hormone-naive patients were free of biochemical progression. The median
      post-treatment PSA level for the biochemically disease-free group was less than
      0.1 ng/mL. In multivariate analysis, only the pretreatment PSA level predicted
      the biochemical outcome. CONCLUSIONS: Hormone-naive patients 62 years of age or
      younger have a high probability of 7-year biochemical progression-free survival
      after permanent interstitial brachytherapy with or without supplemental external
      beam radiotherapy.

PMID- 15491716
TI  - Salvage radiotherapy for men with isolated rising PSA or locally palpable
      recurrence after radical prostatectomy: do outcomes differ?
AB  - OBJECTIVES: To compare, in a retrospective analysis, the outcome of salvage
      external beam radiotherapy (EBRT) for isolated prostate-specific antigen (PSA)
      elevation or palpable local recurrence after radical prostatectomy (RP). METHODS:
      We evaluated 102 men who underwent EBRT from 1993 to 1999, 60 for a rising PSA
      level alone and 42 for palpable local disease after RP. Biochemical disease-free
      survival and overall survival were calculated. Prognostic factors were evaluated
      to determine associations with biochemical disease-free survival. RESULTS: The 5
      year rate of biochemical disease-free survival, local control, freedom from
      distant metastasis, and overall survival for all 102 patients was 38%, 94%, 87%,
      and 88%, respectively. All palpable disease resolved completely after salvage
      EBRT. The greatest 5-year rate of biochemical control (69%) was obtained in
      patients with a pre-EBRT PSA level of 0.5 ng/mL or less. The 5-year overall
      survival rate was significantly better for those who underwent salvage EBRT for a
      rising PSA level than for those with palpable recurrence (96% versus 78%, P =
      0.02). A low pre-EBRT PSA level and a less than 2-year interval from RP to EBRT
      were independent predictors of biochemical failure. Five patients (5%)
      experienced chronic grade 3 or 4 RT-related toxicity. CONCLUSIONS: Salvage EBRT
      provides excellent local control of recurrent disease after RP. Salvage EBRT
      before the development of palpable local disease may confer a survival benefit
      and decrease the risk of metastasis, and durable biochemical control was achieved
      best in those whose pre-EBRT PSA level was 0.5 ng/mL or less. Early referral and
      careful patient selection is vital for salvage EBRT to be of optimal benefit.

PMID- 15491717
TI  - Prostate cancer in native Japanese and Japanese-American men: effects of dietary
      differences on prostatic tissue.
AB  - OBJECTIVES: To investigate the relationship between diet and prostate cancer
      (CaP) among native Japanese (NJ) and second-generation or third-generation
      Japanese-American (J-A) men--focusing on the effects of animal fat and soy on
      prostatic tissues. METHODS: The subjects were 50 Japanese men undergoing radical
      prostatectomy, 25 NJ living in Nagoya, Japan and 25 U.S.-born J-A men, living in
      Los Angeles, California. A priori, the NJ men were believed to be a low-fat, high
      soy group and the J-A men, a high-fat, low-soy group. The studies included
      postoperative measurements of diet (Block questionnaire), body fat
      (bioimpedance), blood, urine, and prostatic biomarkers in malignant and adjacent
      normal tissue, using a tissue microarray made from the original paraffin blocks.
      RESULTS: The NJ and J-A men were similar in age (65 to 70 years old; P <0.05),
      prostate-specific antigen level (7.1 to 8.6 ng/mL), prostate volume (35 to 38
      cm3), and Gleason score (5.6 to 6.6), but their body composition differed. J-A
      men had more body fat (24% versus 19%), higher serum triglyceride levels (245
      versus 106 mg/dL), lower estradiol levels (27 versus 31 ng/mL), and much lower
      urinary soy-metabolite levels (1:3) than NJ men (P <0.02). In both NJ and J-A
      groups, expression of numerous tissue biomarkers separated normal from CaP
      tissue, including markers for apoptosis (Bcl-2, caspase-3), growth factor
      receptors (epidermal growth factor receptor), racemase, 5-lipoxygenase, kinase
      inhibition (p27), and cell proliferation (Ki-67; all P <0.02). Furthermore,
      within both normal and CaP tissues, caspase-3 and 5-lipoxygenase were expressed
      more in NJ than in J-A men (P <0.01). Nuclear morphometry showed that the
      chromatin in each of the four groups (normal versus CaP, NJ versus J-A) was
      different (area under the curve 85% to 94%, P <0.01), despite fundamental genetic
      homogeneity. CONCLUSIONS: NJ and J-A men, products of similar genetics but
      differing environments, were shown to have differences in body composition that
      could influence CaP evolution. The CaP specimens from the NJ and J-A men were
      histologically similar, but tissue biomarker expression, especially of
      lipoxygenase and the caspase family, suggested differing mechanisms of
      carcinogenesis. Differences in nuclear morphometry suggested the additional
      possibility of gene-nutrient interactions.

PMID- 15491718
TI  - Association between lower urinary tract symptoms and erectile dysfunction.
AB  - OBJECTIVES: To assess whether the association between lower urinary tract
      symptoms (LUTS) and erectile dysfunction (ED) is confounded by age or whether
      LUTS represent an independent risk factor for ED. METHODS: Men aged 20 to 80
      years, who were participating in a health-screening project in the area of
      Vienna, completed the International Prostate Symptom Score (IPSS) and the
      International Index of Erectile Function-5. In parallel, all men underwent a
      detailed health evaluation, including physical examination, evaluation of various
      lifestyle factors, and a blood laboratory study with 14 parameters. RESULTS:
      Within the total study population (n = 2858; mean age 45.8 years, range 20 to
      80), the prevalence of LUTS and ED increased statistically significantly with age
      (P <0.0001). In multivariate analysis controlling for age, comorbidities, and
      lifestyle, the IPSS (P = 0.0001), the obstructive score of the IPSS (P = 0.0001),
      nocturia (P = 0.04), and the LUTS bother score (P = 0.002) correlated
      statistically significantly with the presence of ED (International Index of
      Erectile Function-5 score less than 22). The odds ratio for the presence of ED
      was 2.2 (95% confidence interval [CI] 1.8 to 2.8) for LUTS (IPSS greater than 7),
      2.0 (95% CI 1.7 to 2.4) for voiding symptoms, 1.4 (95% CI 1.1 to 1.7) for
      nocturia (score greater than 2), and 2.5 (95% CI 2.0 to 3.1) for the LUTS bother
      score. CONCLUSIONS: The presence of LUTS, in particular voiding symptoms,
      nocturia, and the quality-of-life impairment due to LUTS, is an independent risk
      factor for the presence of ED. These findings have implications for the treatment
      of elderly men with LUTS and open a new area for research.

PMID- 15491719
TI  - Male Sexual Health Questionnaire (MSHQ): scale development and psychometric
      validation.
AB  - OBJECTIVES: To validate a new, self-administered questionnaire for assessing key
      domains of sexual function and satisfaction in aging men with urogenital health
      concerns. METHODS: The initial items were identified by patient interviews,
      review of current reports, and expert panel solicitation. The resulting 25-item
      questionnaire was subjected to psychometric evaluation and refinement using two
      discriminant validity studies in aging men with urogenital symptoms compared with
      age-matched controls. Psychometric tests of reliability, discriminant, and
      criterion validity were performed. RESULTS: Qualitative testing revealed adequate
      comprehension and content validity of the initial item set. Two domains of sexual
      function (ejaculation, erection) were identified in the first discriminant
      validity study, each of which showed a high degree of internal consistency (alpha
      = 0.81 and alpha = 0.90, respectively) and test-retest reliability (r = 0.86 and
      r = 0.87, respectively). Both sexual function domains discriminated well between
      men with and without urogenital manifestations of lower urinary tract symptoms
      (LUTS) and sexual dysfunction (P <0.001). An additional domain of sexual
      satisfaction was added in the second validation study, with similarly high
      internal consistency (alpha = 0.90) and test-retest reliability (r = 0.88). Tests
      of convergent and divergent validity, including correlations with standardized
      scales for depression (Center for Epidemiologic Studies-Depressed Mood Scale),
      sexual function (International Index of Erectile Function), and life satisfaction
      (Fugl-Meyer), confirmed the criterion validity of the new measure. CONCLUSIONS:
      The Male Sexual Health Questionnaire assesses sexual function and satisfaction in
      older men with urogenital symptoms of LUTS and sexual dysfunction. This new
      instrument has excellent psychometric properties and is well suited for use in
      clinical and research settings.

PMID- 15491720
TI  - Integrated analysis examining first-dose success, success by dose, and
      maintenance of success among men taking tadalafil for erectile dysfunction.
AB  - OBJECTIVES: To examine, in a post-hoc, integrated analysis, the first-dose
      success, cumulative success by dose, and maintenance of success among men taking
      tadalafil. Early treatment success is important to men with erectile dysfunction.
      METHODS: In five double-blind, placebo-controlled, 12-week studies, men were
      randomized to placebo (n = 308), tadalafil 10 mg (n = 321), or tadalafil 20 mg (n
      = 258) as a fixed dose. The Sexual Encounter Profile (SEP) diary questions
      assessed success from three perspectives: (a) first-dose success; (b) cumulative
      proportion of men with first success by dose; and (c) maintenance of success
      among men with first-dose success. RESULTS: With the first dose, significantly
      greater proportions of men taking tadalafil 10 and 20 mg versus placebo achieved
      successful erection (SEP-Q1: 85% and 90% versus 66%, respectively), successful
      penetration (SEP-Q2: 74% and 79% versus 47%, respectively), successful
      intercourse (SEP-Q3: 56% and 67% versus 31%, respectively), and were satisfied
      overall with their sexual experience (SEP-Q5: 36% and 47% versus 15%,
      respectively; all P <0.001). The proportion of men achieving first success
      increased with continued dosing, reaching a plateau between doses 4 and 8 at
      approximately 95% (SEP-Q2), 90% (SEP-Q3), and 81% (SEP-Q5). For men with first
      dose success, the subsequent success rate during the 12-week period was
      significantly greater for men taking tadalafil 10 and 20 mg versus placebo (all P
      <0.001; SEP-Q2: 85% and 91% versus 75%; and SEP-Q3: 81% and 88% versus 64%,
      respectively). CONCLUSIONS: Most men taking tadalafil achieved successful
      erection, penetration, and intercourse after one dose and maintained the success
      over time. Because success increased with continued use, men who do not respond
      initially should continue treatment to increase the likelihood of treatment
      success.

PMID- 15491721
TI  - Comprehensive surgical treatment of prune belly syndrome: 17 years' experience
      with 32 patients.
AB  - OBJECTIVES: To describe the results of comprehensive surgical management of prune
      belly syndrome. METHODS: Thirty-two patients were evaluated and treated for
      abdominal and genitourinary abnormalities. The surgical procedure, including
      simultaneous abdominoplasty, bilateral orchiopexy, and urinary tract
      reconstruction, was performed according to individual needs. At follow-up, the
      urinary tract, abdominal, and genital anatomy and function were evaluated.
      RESULTS: The upper urinary tract anatomy and function were stabilized in 30
      patients, and no vesicoureteral reflux was found postoperatively. The bladder
      drainage was adequate in 29 patients, and 4 presented with recurrent bacteriuria.
      Abdominoplasty improved flaccidity in 29 patients. Adequate testicular position
      and consistency were obtained in 54 testes. Complications included acute tubular
      necrosis (1 patient) and ureterovesical obstruction (3 patients). CONCLUSIONS:
      Individualized comprehensive surgical management of prune belly syndrome is
      effective, with an acceptable incidence of complications and excellent long-term
      results.

PMID- 15491724
TI  - Results of dorsal midline plication in children with penile curvature and
      hypospadias.
AB  - OBJECTIVES: To present our initial results using dorsal midline (12-o'clock
      position) plication in children with penile curvature and hypospadias. METHODS:
      Twenty-five children with hypospadias and ventral curvature confirmed after
      artificial erection underwent dorsal midline plication and hypospadias repair.
      Ventral curvature was corrected by making a 5 to 10-mm-long vertical incision
      through the tunica albuginea at the dorsal midline and approximating the outer
      edges of the incision with a monofilament polydioxanone stitch. RESULTS: One
      plication suture was needed in 15 patients. In 8 patients with mid-shaft
      hypospadias and 2 with proximal penile hypospadias, two and three sutures were
      needed, respectively. In none of the patients was division of the urethral plate
      needed, except for one with proximal hypospadias. No complications were
      encountered during a mean follow-up of 9 months (range 5 to 34). CONCLUSIONS: We
      believe that most cases of penile curvature with hypospadias can be corrected
      using dorsal midline plication of the tunica albuginea. Although long-term follow
      up is necessary after puberty to confirm any erectile or sensory advantage, this
      approach might be considered whenever plication is to be performed.

PMID- 15491726
TI  - A simple maneuver to replace dislodged laparoscopic port.
AB  - Inadvertent dislodgment of laparoscopic port can occur despite preventive
      measures. We describe a simple maneuver to replace a dislodged port using a
      palpation probe. The principle is analogous to that of using a laparoscopic
      grasping forceps. It is easy to perform, quick, reliable, safe, and particularly
      useful for the laparoscopists in training.

PMID- 15491727
TI  - Laparoscopic Mitrofanoff appendicovesicostomy.
AB  - A novel technique of performing fully laparoscopic Mitrofanoff
      appendicovesicostomy in the management of neurogenic bladder is described. All
      steps, including appendix harvesting and extravesical appendiceal-vesical
      anastomosis with flap-valve mechanism creation, were completed laparoscopically
      and provided satisfactory preliminary clinical results. Additional studies are
      necessary for the evaluation of this novel technique.

PMID- 15491728
TI  - An unusual case of ureteropelvic junction obstruction.

PMID- 15491729
TI  - Isolated renal vein thrombosis after blunt trauma.
AB  - Renal vein thrombosis typically occurs in the setting of nephrotic syndrome,
      tumor thrombus, primary retroperitoneal processes with vein compression, oral
      contraceptive use, steroid therapy, transplanted kidney, or trauma. Trauma
      induced renal vein thrombosis usually presents in combination with renal arterial
      or parenchymal injury. We report a case of isolated renal vein thrombosis
      secondary to blunt abdominal and flank trauma. The diagnosis was made with
      computed tomography, which revealed a filling defect in the affected renal vein
      and persistent nephrogram on delayed images. In general, conservative management
      is the preferred treatment approach with anticoagulation.

PMID- 15491730
TI  - Unexpected response of hormone-refractory prostate cancer to treatment with an
      antileukemic chemotherapy regimen.
AB  - Our patient was a 61-year-old man with hormone-refractory prostate cancer and a
      rapidly rising serum prostate-specific antigen level. During the course of
      therapy for prostate cancer, abnormal blood counts and subsequent bone marrow
      biopsy led to a diagnosis of acute lymphoblastic leukemia. He was treated with a
      chemotherapeutic regimen in standard use for lymphoblastic leukemia, which
      resulted in an unusual response of his prostate cancer, with declining serum
      prostate-specific antigen levels that had reached undetectable levels at the time
      of the patient's death from acute sepsis and leukemic relapse. Autopsy showed
      minimal evidence of prostate cancer, localized to the prostate.

PMID- 15491731
TI  - Metastatic cancer to the renal pelvis: a novel approach to management.
AB  - We describe a novel application of percutaneous renal surgery for the management
      of an unusual and challenging urologic problem. Two patients with symptomatic,
      metastatic adenocarcinoma in the renal pelvis were treated with percutaneous
      resection. The lesion was in a solitary kidney in 1 patient, and was bilateral in
      the second. Percutaneous resection resulted in complete relief of symptoms and
      obstruction. Although both patients ultimately died of their primary disease,
      their quality of life was significantly improved in the interim. Percutaneous
      resection of renal pelvic tumors is accepted management for select patients with
      upper tract transitional cell carcinoma. These 2 cases demonstrated both an
      unusual presentation for metastatic adenocarcinoma and an expanded application
      for percutaneous renal surgery.

PMID- 15491732
TI  - Spinal cord compression and lung metastasis of Wilms' tumor in a pregnant
      adolescent.
AB  - Wilms' tumor in adults is rare, and no treatment guidelines have been
      established. Spinal cord compression has also been rarely reported in all age
      groups. In this case report, we present a 19-year-old adolescent with recurrent
      Wilms' tumor, a paraspinal dumbbell mass, metastatic involvement of the vertebral
      bodies, lung metastasis, and pregnancy. To our knowledge, this is the first
      report of a pregnant patient with Wilms' tumor who had to undergo immediate
      chemotherapy with vincristine and actinomycin-D owing to spinal cord compression
      at 25 weeks of pregnancy. After delivery, complete remission was maintained with
      a regimen of ifosfamide, carboplatin, and etoposide and vincristine, actinomycin
      D, and cyclophosphamide. No teratogenic or other toxic effects of vincristine or
      actinomycin-D were observed in the fetus.

PMID- 15491733
TI  - Testicular granulocytic sarcoma, a source of diagnostic confusion.
AB  - We report a case of granulocytic sarcoma of the testis without hematologic
      manifestations. The patient was disease free 7 years after the initial
      presentation. The initial pathology interpretation favored a diagnosis of high
      grade non-Hodgkin's lymphoma but additional histologic staining confirmed the
      diagnosis of granulocytic sarcoma. Only 2 cases of testicular granulocytic
      sarcoma without an associated hematologic disorder have been described. To our
      knowledge, this is the third reported case. The diagnosis of this rare tumor is
      difficult and should be in the differential diagnosis when non-Hodgkin's lymphoma
      is considered.

PMID- 15491734
TI  - Synchronous solitary metastasis of transitional cell carcinoma of the bladder to
      the testis.
AB  - Primary tumors known to metastasize to the testis, in order of decreasing
      frequency, are prostate, lung, gastrointestinal tract, melanoma, and kidney
      tumors. Metastasis from bladder cancer to the testis is extremely rare, occurs
      with advanced and metastatic disease, and is usually a finding at autopsy. We
      report a rare, and probably the first, case of solitary and synchronous
      metastatic transitional cell carcinoma of the bladder to the testis, discovered
      on the preoperative workup. An incidentally discovered testicular mass in a man
      with high-grade, invasive bladder cancer should be considered a metastatic lesion
      until proven otherwise.

PMID- 15491735
TI  - Renal cell cancer in solitary kidney after donor nephrectomy.
AB  - The occurrence of renal cell carcinoma in the solitary remnant kidney after donor
      nephrectomy is rare and, to our knowledge, has not been previously reported. We
      encountered 2 such patients in whom cancer occurred 19 and 40 years after the
      donation. Both patients underwent successful partial nephrectomy for the tumor
      using two different techniques.

PMID- 15491736
TI  - Quartz stones: spurious or iatrogenic?
AB  - We describe 2 cases of spurious quartz-containing calculi; the first patient
      driven and the second iatrogenic. An iatrogenic etiology can occur after the use
      of holmium:yttrium-aluminum-garnet laser energy because the fiber tip is composed
      of quartz. To make the diagnosis of a spurious stone, a high degree of suspicion
      is essential. A quartz stone should prompt the diagnosis of a factitious disorder
      in the absence of the appropriate surgical history. Psychological counseling
      and/or referral to a pain management clinic should be considered in such cases.

PMID- 15491737
TI  - Late recurrence of renal cholesteatoma after 15 years.
AB  - We report a late recurrence of a cholesteatoma of the left kidney after 15 years.
      Both the initial case and the recurrence were treated by endourologic and
      percutaneous approaches.

PMID- 15491738
TI  - Community-acquired methicillin-resistant Staphylococcus aureus prostatic abscess.
AB  - We present a 43-year-old man with a history of intravenous drug abuse who
      presented to the emergency department with a 5-week history of lower urinary
      tract symptoms. On digital rectal examination, a firm prostate with exquisite
      tenderness was noted. Computed tomography scan of the pelvis with contrast
      demonstrated a 4.4 by 2.7-cm prostatic abscess in the right lobe. Suppurative
      fluid was expressed from the right prostatic lobe during transurethral resection
      of the prostate. Cultures of blood and suppurative prostatic fluid grew
      methicillin-resistant Staphylococcus aureus.

PMID- 15491739
TI  - Identification of interstitial cells of Cajal in human urinary bladder: concept
      of vesical pacemaker.
AB  - OBJECTIVES: To determine whether, given the presence of interstitial cells of
      Cajal (ICCs) in organs that discharge slow waves, such as the gastrointestinal
      tract, such cells could also be present in the human urinary bladder (UB) and
      might exist in great numbers in the bladder dome, constituting the "primary
      pacemaker" from which slow waves spread to the body of the UB. This hypothesis
      was based on previous studies that had demonstrated the vesical electric waves
      starting in the dome and spreading caudad. METHODS: Specimens (0.5 x 0.5 cm) from
      different vesical locations were obtained from the cystectomized UB of 18
      patients (12 men, 6 women, mean age 42.6 +/- 3.8 years) with bladder cancer.
      Fixed sections were prepared and subjected to c-kit immunohistochemistry.
      Controls for the antiserum specificity consisted of incubation of the tissue with
      normal rabbit serum substituted for the primary antiserum. RESULTS: Fusiform, c
      kit positive, and ICC-like cells were detected in the vesical muscle layers; they
      had dendritic processes. They occurred separately or were connected through the
      dendritic processes to form a cellular network. An accumulation of ICCs
      surrounded by a connective tissue layer was detected in all the dome specimens.
      Mast cells occurred in the vesical mucosa and submucosa; they were c-kit positive
      but had a rounded body with no dendritic processes. CONCLUSIONS: We identified
      cells in the UB with morphologic and immunologic phenotypes similar to the ICCs
      of the gut. An accumulation of these cells, detected in the vesical dome, seems
      to constitute the "primary" vesical pacemaker that initiates the slow waves that
      spread to the other vesical walls. We believe that a deficiency or absence of
      these cells may be involved in vesical motility disorders. Additional studies are
      needed to delineate the role of these cells in UB physiology and pathologic
      conditions.

PMID- 15491740
TI  - Metastases of prostate cancer express estrogen receptor-beta.
AB  - OBJECTIVES: To examine estrogen receptor-beta (ERbeta) expression in prostate
      cancer (CaP) metastases, thereby providing a basis for conducting estrogen
      therapy studies in patients with metastatic CaP. Advanced androgen-independent
      CaP is a serious health problem with no effective treatment at present. Estrogens
      have been reported to inhibit the growth of CaP cells in androgen-free
      environments. Recent reports have shown that the prostatic epithelium and primary
      CaP cells express ERbeta, with decreased expression of ERbeta accompanying CaP
      progression. It has been proposed that ERbeta may play a role in the growth
      regulation of prostate cells. The targeting of ERs by selective ER modulators
      might be an effective method of treating advanced CaP. METHODS: The anti-ERbeta
      antibody GC17 was used in immunohistochemistry to characterize the expression of
      ERbeta in CaP metastasis specimens (n = 60) obtained from 20 patients who had
      died of CaP. Statistical analyses were performed to evaluate the association of
      ERbeta expression with clinical parameters, including prostate-specific antigen
      levels, radiotherapy, and estrogen exposure. RESULTS: Nuclear ERbeta staining was
      detected in all bone CaP metastases (33 of 33) and nonosseous CaP metastases (27
      of 27). However, a large variability in the percentage of immunoreactive cells
      (5% to 100%) was found among patients, as well as among individual patient
      samples. A statistically significant negative association between nuclear ERbeta
      staining and estrogen exposure (P = 0.05) was detected. CONCLUSIONS: Our data
      have shown that ERbeta is expressed in CaP metastases, validating the initiation
      of studies to evaluate selective ER modulators for treatment of advanced CaP.

PMID- 15491741
TI  - Prostate cancer molecular markers GSTP1 and hTERT in expressed prostatic
      secretions as predictors of biopsy results.
AB  - OBJECTIVES: To develop noninvasive diagnostic tools for the early detection of
      prostate cancer (PCa). Current screening for PCa lacks sensitivity and
      specificity. Two molecular markers, telomerase activity and aberrant methylation
      of the glutathione S-transferase P1 (GSTP1) promoter, are found in more than 90%
      of PCa specimens. Additionally, these markers can be detected in bodily fluids
      such as urine and postprostatic massage urethral washes. METHODS: Expressed
      prostatic secretions (EPS) from men being evaluated for PCa were analyzed for
      human telomerase reverse transcriptase (hTERT) expression (the critical factor
      for telomerase activity) and GSTP1 methylation status. The results were compared
      with the prostate needle biopsy findings. RESULTS: EPS could be obtained from 86%
      of all subjects, and 90% of these samples yielded sufficient RNA and/or DNA for
      assaying. hTERT expression from EPS (n = 49) had 36% sensitivity and 66%
      specificity, and GSTP1 methylation from EPS (n = 58) had 46% sensitivity and 56%
      specificity for the detection of PCa. The combined analysis (n = 32) of hTERT and
      GSTP1 had 73% sensitivity and 43% specificity, giving a positive predictive value
      of 40% and a negative predictive value of 75%. CONCLUSIONS: These results
      demonstrate that EPS can be successfully obtained and easily tested for hTERT
      expression and GSTP1 methylation. Tests with a high negative predictive value,
      such as our combination assay results, could be useful in augmenting current PCa
      diagnostic procedures. For example, the examination of EPS for hTERT and GSTP1
      methylation in patients with an elevated prostate-specific antigen level might be
      used in predicting which patients will have negative biopsies. The use of this
      assay could potentially eliminate up to 30% of costly and invasive needle
      biopsies.

PMID- 15491742
TI  - Localization and expression of TSP50 protein in human and rodent testes.
AB  - OBJECTIVES: To present our recent observations obtained from the continuing
      characterization of the TSP50 gene pertaining to its evolutionary importance and
      behavior in human testicular germ cell tumors. Previous studies have reported
      that expression of the human TSP50 gene is testes specific. Its product is
      similar to many serine proteases but possesses its own unique features. In
      addition, TSP50 is abnormally activated in most tested patients with breast
      cancer. METHODS: Testicular tissue from rats, mice, and humans was obtained
      through biopsy or orchiectomy. The expression of the TSP50 protein was determined
      using immunohistochemical staining and Western blotting techniques. RESULTS: The
      Western blot results showed that the polyclonal anti-human TSP50antibody reaction
      pattern in both rodent testes was the same as that observed in the human testes.
      In addition, the immunohistochemical staining patterns in the human, mouse, and
      rat testes were similar. We also discovered that expression of TSP50 was largely
      downregulated in all testicular germ cell tumors examined by immunohistochemical
      analysis. CONCLUSIONS: The results of our studies suggest that the TSP50 gene
      could be of evolutionary importance in mammalian reproduction. Unlike the results
      generated from patients with breast cancer, in whom upregulation of the TSP50
      gene correlates with disease development, the TSP50 gene was downregulated in
      patients with seminoma. This information indicates that altered expression levels
      of the TSP50 gene in different microenvironments are associated with different or
      distinct types of human cancer.

PMID- 15491743
TI  - Association between vitamin D receptor gene polymorphisms and fasting idiopathic
      hypercalciuria in recurrent stone-forming patients.
AB  - OBJECTIVES: To investigate the association between fasting idiopathic
      hypercalciuria (IHc), defined as IHc in the fasting state associated with normal
      parathyroid function, and ApaI, BsmI, and FokI polymorphisms of the vitamin D
      receptor (VDR) gene in 159 hypercalciuric recurrent stone formers. IHc
      contributes to the formation of calcium kidney stones in more than one half of
      reported cases. METHODS: We examined 62 patients with fasting IHc (24 women, mean
      age 42.8 +/- 11.1 years, body mass index 25.7 +/- 4.8 kg/m2), 97 patients with
      absorptive IHc (41 women, mean age 43.5 +/- 10.8 years, body mass index 26.1 +/-
      4.4 kg/m2), and 124 healthy control subjects (52 women, mean age 41.9 +/- 10.4
      years, body mass index 25.4 +/- 5.1 kg/m2) without a history of nephrolithiasis
      and without IHc. The bone mass density and VDR genotype and haplotype frequencies
      were determined in the studied populations. RESULTS: A reduced bone mass density
      was observed in fasting IHc patients compared with absorptive IHc patients (P =
      0.009) and control subjects (P = 0.006). The prevalence of ApaI and BsmI VDR
      genotypes and alleles in patients with fasting IHc was significantly different
      statistically (P <0.05) from that observed in patients with absorptive IHc and
      control subjects, and the ba haplotype was overrepresented in these patients. No
      statistically significant difference in the distribution of FokI VDR genotypes
      and alleles was found between the studied groups. CONCLUSIONS: Our results
      suggest a genetic association between 3' VDR alleles, fasting IHc, and reduced
      bone mass density in patients with recurrent stone formation.

PMID- 15491744
TI  - Association of nucleophosmin/B23 mRNA expression with clinical outcome in
      patients with bladder carcinoma.
AB  - OBJECTIVES: To determine whether nucleophosmin/B23 mRNA expression in bladder
      carcinoma predicts recurrence, progression, and survival. METHODS: Real-time
      reverse transcriptase-polymerase chain reaction was performed on 50 fresh cancer
      specimens. The change in the cycle of threshold (Ct)was the difference in the Ct
      values derived from the nucleophosmin/B23 gene assayed and the 18S ribosomal RNA
      control [Ct (18S)-Ct (nucleophosmin/B23)]. RESULTS: Fifty patients diagnosed with
      bladder cancer were followed up postoperatively for a median of 24 months.
      Overexpression of nucleophosmin/B23 mRNA was observed in 37.1% of patients with
      Stage pT1 and 73.3% of those with pT2-T4 disease. Nucleophosmin/B23
      overexpression was not associated with tumor grade (P = 0.163) but was associated
      with bladder cancer recurrence (68.2%) and progression (88.9%) when adjusted for
      the effects of clinical stage. Multivariate analysis revealed that the overall
      tumor stage and nucleophosmin/B23 mRNA overexpression were important prognostic
      indicators for bladder carcinoma (P <0.05). Patients with nucleophosmin/B23 mRNA
      overexpression were at a significantly greater risk of disease recurrence and
      progression than those with low expression of nucleophosmin/B23 mRNA.
      CONCLUSIONS: Overexpression of nucleophosmin/B23 mRNA was independently
      associated with bladder cancer recurrence and progression. In patients with
      muscular invasion disease, overexpression of nucleophosmin/B23 mRNA was
      associated with the greatest risk of recurrence and progression, suggesting a
      potential rationale for early definitive therapy in these patients.

PMID- 15491745
TI  - Antineoplastic effect of gemcitabine in an animal model of superficial bladder
      cancer.
AB  - OBJECTIVES: To evaluate the safety and efficacy of gemcitabine in an animal model
      of superficial bladder cancer because of the promising results for treatment of
      patients with advanced urothelial carcinoma using gemcitabine. The substantial
      failure rate and toxicity of currently available intravesical agents for treating
      superficial bladder cancer emphasize the need for alternative drugs. METHODS: The
      mouse bladder tumor (MBT-2) model was used in female C3H/eb mice to evaluate
      gemcitabine toxicity (n = 45) and efficacy (n = 402). RESULTS: Treatment with
      varying doses (0.5, 2.5, and 10 mg) of intravesical gemcitabine was well
      tolerated with no demonstrable side effects. No statistically significant
      differences in the histologic changes in the bladder wall were observed among the
      various treatment groups. The efficacy of the drug was tested in two sets of
      experiments and showed a statistically significant decrease in the bladder weight
      of the animals treated with gemcitabine compared with those treated with
      phosphate-buffered saline or untreated controls (61.4 +/- 24.1 mg versus 106.2 +/
      50 mg and 105.5 +/- 46 mg, respectively [P = 0.0001], for an aggressive tumor
      variant). In the second set of experiments, gemcitabine was given both
      intraperitoneally and intravesically and resulted in a lower bladder weight (44.5
      +/- 15.75 mg and 59.71 +/- 22.5 mg, respectively) compared with the control
      groups (116.43 +/- 53.91 mg and 122.29 +/- 50 mg, respectively, P = 0.0004).
      CONCLUSIONS: The results of the present study indicate that repeated doses of
      gemcitabine can be safely administered intravesically to C3H/eb mice. This drug
      displayed significant antineoplastic activity against superficial bladder cancer.

PMID- 15491746
TI  - Critical evaluation of secondary cytoreduction in recurrent ovarian cancer.
AB  - OBJECTIVE: The optimal strategy for salvage therapy in patients who suffer from
      ovarian cancer recurrence after a disease-free interval is not established. The
      objective of this paper is to analyze the existing published data on salvage
      surgery in this setting. METHODS: A retrospective review of the English
      literature was done looking at studies addressing the role of secondary
      cytoreductive surgery in recurrent ovarian cancer. A number of parameters were
      collected from these studies and analyzed, including patients' characteristics,
      outcome of secondary cytoreduction, perioperative complications, postoperative
      therapy, and survival. In a parallel analysis, we reviewed the outcome of
      patients treated with salvage chemotherapy without surgery in similar clinical
      settings. RESULTS: Optimal cytoreduction was achievable in 38-87% of the study
      populations reviewed with acceptable perioperative complications and mortality.
      The attempt to analyze the impact of secondary cytoreduction on survival was
      limited by (1) the inter-investigator differences in defining optimal
      cytoreduction, (2) the heterogeneity of the patients included, (3) and the lack
      of information on postoperative therapy. All the studies suggest that patients
      left with no gross residual disease after secondary cytoreduction seem to benefit
      from prolonged survival in the range of 44-60 months. Current data reveal that
      the use of combination chemotherapy without surgery for salvage treatment of
      recurrent ovarian cancer can be associated with prolonged median survival
      reaching up to 35 months. CONCLUSION: The available data suggest a benefit for
      secondary surgical cytoreduction in recurrent ovarian cancer. This needs to be
      considered in the light of recent data reporting prolonged survival with the use
      of combination salvage chemotherapy without surgery. Currently, it is not known
      if a salvage strategy combining surgery and multiagent chemotherapy regimens will
      have a survival benefit over chemotherapy alone. Hopefully, current ongoing
      prospective trials will answer this question.

PMID- 15491748
TI  - HMOCC-1, a human monoclonal antibody that inhibits adhesion of ovarian cancer
      cells to human mesothelial cells.
AB  - OBJECTIVES: Ovarian carcinoma is one of the most common gynecologic cancers and
      shows the worst prognosis since current therapies are not sufficiently effective
      at achieving and maintaining remission. To develop new treatment, a monoclonal
      antibody recognizing human ovarian cancer cells was raised in KM mice. METHODS: A
      human monoclonal antibody targeting RMG-I (an ovarian carcinoma cell line) was
      established with hybridomas of myeloma cells and spleen cells from KM mice. The
      immunohistochemical reactivity of various types of ovarian carcinoma and other
      tumors was investigated. RMG-I cells were treated with N-glycosidase F, NaOH,
      H(2)SO(4), and Gal NAC-alpha-benzyl to investigate the target antigens by Western
      blotting. The effect of HMOCC-1 on adhesion of RMG-I cells to cultured human
      mesothelial cells was also investigated. RESULTS: The new human monoclonal
      antibody, HMOCC-1, was an immunoglobulin M that recognized ovarian epithelial
      carcinoma. Immunohistochemical staining revealed HMOCC-1 positivity in 83.2% of
      ovarian carcinomas. The antigen recognized by HMOCC-1 was apparently a
      glycoprotein since Western blotting yielded a broad band (34.8-49.1 kDa). HMOCC-1
      inhibited the attachment of RMG-I cells to monolayers of cultured peritoneal
      mesothelial cells in a concentration-dependent manner. CONCLUSIONS: This new
      human monoclonal antibody reacted with most ovarian cancers tested. The antigen
      recognized by HMOCC-1 is a glycoprotein located on the cell membrane. Inhibition
      of the attachment of RMG-1 cells to mesothelial cells by HMOCC-1 suggests a
      potential role for this antibody in the treatment of ovarian cancer.

PMID- 15491747
TI  - Expression of DCC and netrin-1 in normal human endometrium and its implication in
      endometrial carcinogenesis.
AB  - OBJECTIVE: Although DCC has been considered as a candidate tumor suppressor, the
      roles it plays in the uterine endometrium and in the carcinogenic process remains
      unclear. To define these roles more clearly, we examined the expression of DCC
      and its ligand, netrin-1, in the normal endometrium and in endometrial cancer.
      METHODS: The expression of DCC and netrin-1 in normal endometrial glands and in
      cancer cell lines was examined by RT-PCR and immunohistochemistry. The effects of
      exogenous DCC and netrin-1 expression were observed together with the respective
      expression vector transfection. RESULTS: Endometrial glands in the proliferative
      and early secretory phase expressed both DCC and netrin-1, but glands in the late
      secretory phase tended to silence DCC expression. In addition, all of the
      endometrial cancer cell lines lost normal DCC expression. Restored DCC expression
      in the cancer cell lines in the absence of netrin-1 induced apoptosis. However,
      no changes were observed in the presence of netrin-1. CONCLUSION: Our
      observations suggest that DCC/netrin-1 signaling may commit cells to the
      transition of endometrial gland architecture or function from a proliferating to
      a secretory phase. In addition, the silencing of DCC expression may contribute to
      the escape of endometrial cancer cells from a DCC-regulated apoptotic program,
      thereby promoting malignant phenotypes.

PMID- 15491749
TI  - Expression of leptin and leptin receptors in gestational trophoblastic diseases.
AB  - OBJECTIVES: To investigate the expression profile of leptin and leptin receptors
      in gestational trophoblastic diseases (GTDs). METHODS: Using immunohistochemical
      staining on archival paraffin-embedded tissue sections, we studied the expression
      of leptin and leptin receptor in hydatidiform moles, with gestational age-matched
      normal first-trimester placenta used as control. A total of 38 cases of
      hydatidiform moles were studied, including 20 complete moles (CHMs) and 18
      partial moles (PHMs). Among them, 10 cases of the CHM group and 8 cases of the
      PHM group subsequently developed residual trophoblastic disease (RTD). In
      addition, two cases of choriocarcinoma and three cases of placental site
      trophoblastic tumor (PSTT) were also studied. Reverse transcriptase-polymerase
      chain reaction (RT-PCR) was further performed using RNA extracted from frozen
      tissue (five CHMs, four PHMs and nine normal first-trimester placenta) to study
      the expression of leptin and individual leptin receptor isoforms at the
      transcription level. RESULTS: In all tissue sections, immunostaining signal was
      shown in the cytoplasmic compartment of cytotrophoblasts and
      syncytiotrophoblasts, with much stronger staining in the former. Significantly
      higher immunostaining intensity was shown for both leptin (P < 0.05) and leptin
      receptor (P < 0.001) in both CHMs and PHMs compared to normal first-trimester
      placenta. There was no significant difference between those cases subsequently
      developing RTD and those which did not (P > 0.05). In the choriocarcinoma and
      PSTT cases, intense immunostaining was found in the tumor cells. RT-PCR revealed
      that the expression of leptin and all leptin receptor isoforms were significantly
      higher in both CHMs and PHMs than in normal placenta (P < 0.05). CONCLUSIONS:
      There is up-regulated expression of leptin and leptin receptor in GTDs. However,
      there is no obvious correlation with the development of RTD. The exact role
      played by leptin and its receptors in the pathogenesis of GTDs awaits further
      investigations.

PMID- 15491750
TI  - Placental leucine aminopeptidase (P-LAP) expression is associated with
      chemosensitivity in human endometrial carcinoma.
AB  - OBJECTIVE: Although treatment for advanced or recurrent endometrial carcinoma has
      improved over recent years with the introduction of paclitaxel- and platinum
      based chemotherapy, in most, the disease remains incurable because of resistance
      to chemotherapy. In the previous study, we have shown that placental leucine
      aminopeptidase (P-LAP) is associated with poor prognosis. The objective of this
      study was to determine whether P-LAP expression affects the chemosensitivity in
      endometrial carcinoma patients. METHODS: Here, we investigated the effect of P
      LAP to response for paclitaxel and carboplatin in advanced and recurrence
      endometrial carcinoma. Furthermore, we transfected P-LAP cDNA into endometrial
      carcinoma cells (AMEC) and investigated cell growth and apoptosis by paclitaxel
      or carboplatin. RESULTS: In 15 of 17 patients, P-LAP was positive. Twelve of
      seventeen patients were evaluable for response. Among the eight patients strongly
      positive for P-LAP, only two patients (25%) showed PR. However, all four patients
      who were weakly positive for P-LAP showed either complete response (CR) or
      partial response (PR). P-LAP overexpressor (P-LAP2 and P-LAP8) and a vector
      control were used to assay chemosensitivity. P-LAP2 clone displayed a 1.7-fold
      increase in IC(50) against paclitaxel and carboplatin when compared with the
      vector control, and P-LAP8 clone displayed a 1.6-fold increased in IC(50) against
      paclitaxel and carboplatin when compared with V1. Compared to vector control
      cells, apoptotic effect by carboplatin treatment was clearly inhibited in P-LAP2
      and P-LAP8 cells. Carboplatin, 10(-6) M, induced the 12.5-fold rate of apoptosis
      compared to that without treatment at 48 h in vector control cells. However, in P
      LAP2 and P-LAP8 clones, 10(-6) M carboplatin induced only 3.2- and 5.1-fold rates
      of apoptosis, respectively, compared to that of without treatment. CONCLUSIONS: P
      LAP was suggested to be involved in reducing chemosensitivity and may be a
      therapeutic target in endometrial carcinoma.

PMID- 15491752
TI  - Pretreatment serum hemoglobin level and a preliminary investigation of
      intratumoral microvessel density in advanced ovarian cancer.
AB  - OBJECTIVE: The primary aim of this study was to evaluate the prognostic and
      predictive value of pretreatment serum hemoglobin level (Hb) in advanced ovarian
      cancer; second aim was to perform a preliminary investigation of intratumoral
      microvessel density (IMD). METHODS: The influence on survival and response to
      treatment of several clinico-pathological features, including Hb, was analyzed in
      72 patients with advanced ovarian cancer. IMD was assessed in tumor specimens of
      25 of the 72 patients to compare three different endothelial markers: anti
      FactorVIII, anti-CD31 and anti-CD34. In this subgroup of patients, a preliminary
      analysis of the prognostic and predictive value of IMD, and its relationship with
      Hb and other clinico-pathological features, was performed. RESULTS: Hb >or= 12
      g/dl was significantly associated with a better overall survival in univariate
      analysis (P = 0.0181) and was the only independent prognostic variable in
      multivariate analysis (P = 0.0160). Hb was directly related to progression-free
      survival (P = 0.0240) and complete response to treatment (P = 0.016). In the
      preliminary investigation of IMD, mean microvessel count did not show any
      significant difference among the three endothelial markers used, but anti-CD34
      revealed a more consistent staining reaction. The relationship between IMD and
      complete response to treatment was found near to statistical significance (P =
      0.05); Hb and IMD were inversely related (r = -0.47; P = 0.045). CONCLUSIONS: Hb
      has a prognostic and predictive value in advanced ovarian cancer. In our
      preliminary study, which was performed on a limited number of patients, we found
      anti-CD34 to be an optimal marker for IMD determination, IMD to be a possible
      predictive factor of complete response to treatment, and IMD and Hb to be
      inversely related.

PMID- 15491751
TI  - Lysophosphatidic acid enhances epithelial ovarian carcinoma invasion through the
      increased expression of interleukin-8.
AB  - OBJECTIVE: We previously reported that lysophosphatidic acid (LPA) stimulates
      cellular invasion of ovarian cancer (OVCA) cells by enhancing membrane-type-1
      matrix metalloproteinase (MT1-MMP)-mediated activation of MMP2. Here, we
      investigate a second mechanism in which LPA enhances cellular invasion through
      the increased expression of IL-8, independent of the expression or activation of
      MMP2. METHODS: Epithelial ovarian carcinoma cells (DOV 13) were exposed to LPA
      (80 microM) and IL-8 (100 ng/ml) for 24 h. IL-8 expression was quantified by
      enzyme-linked immunosorbent assay (ELISA). Cellular invasion (Matrigel invasion),
      migration (colloidal gold), and urinary-type plasminogen activator (uPA) activity
      (colorimetric assay) were quantified. Conditioned medium was also assayed for MMP
      activation and expression by SDS-PAGE gelatin zymography, ELISA, and Western
      blotting. In addition, IL-8 neutralizing antibody and MMP inhibitors were
      employed. RESULTS: Our results found LPA to increase IL-8 expression threefold.
      IL-8 did not affect cellular migration, MMP2 activation, or uPA expression.
      However, exposure to various concentrations of IL-8 increased cellular
      invasiveness. Using an IL-8 blocking antibody and various MMP inhibitors, we
      determined that the increase in invasion was IL-8-dependent, while independent of
      the activation of MMP2 or MMP9. We further determined IL-8 exposure increased the
      expression of matrilysin (MMP7). Cells exposed to LPA and IL-8 resulted in a
      synergistic effect on cellular invasion. Adding the IL-8 blocking antibody,
      slightly decreased cellular invasion, indicating LPA in part, increases cellular
      invasion through the increased expression of IL-8. CONCLUSION: We have identified
      a separate mechanism of enhanced cellular invasion, which is independent of MMP2
      activation and involves the increased expression of IL-8 and subsequent increased
      expression of MMP7.

PMID- 15491753
TI  - Versatile lotus petal flap for vulvoperineal reconstruction after gynecological
      ablative surgery.
AB  - OBJECTIVE: The objective of the present work was to assess the efficacy and
      complications of the use of the lotus petal flap in the vulvoperineal
      reconstruction among female patients treated for vulvar malignancies. METHODS:
      Between December 2000 and April 2003, five patients underwent vulvoperineal
      reconstructions with the fasciocutaneous skin flaps elevated from gluteal folds
      immediately after vulvoperineal ablative surgeries at National Cancer Center
      Hospital, Tokyo, Japan. RESULTS: The mean surface area of vulvoperineal tissue
      defects was 157.9 cm(2) (64.0-195.0 cm(2)), which could be filled completely by
      bilateral lotus petal flaps. The mean length of follow-up was 18 months (7-32
      months). All flaps successfully survived without fatal necrosis. In postoperative
      follow-up, all patients had no complaint of pain and no abnormal sensation at the
      site of flap or at the donor site, and the lotus petal flap caused no severe
      damage to excretion, mobility of the hip, or the sensation in the vulvoperineal
      area. The gluteal fold could make the donor-site scar stand out in all patients.
      CONCLUSION: The lotus petal flap is thought to be one of the most ideal
      reconstructive procedures for vulvoperineal region from various viewpoints of
      oncology, function, wound healing, and cosmetic surgery.

PMID- 15491754
TI  - HER-2/neu expression in Paget disease of the vulva and the female breast.
AB  - OBJECTIVES: Paget disease of the vulva is a rare lesion that accounts for <1% of
      vulva neoplasms. A 12% prevalence of invasive Paget carcinoma and a 4% prevalence
      of associated adenocarcinomas are described. Furthermore, a high recurrence rate
      of 30% after surgical therapy is observed. This study aims to search for
      therapeutic strategies for recurrent Paget disease, which are less mutilating and
      less aggressive than reexcision, x-ray therapy, or chemotherapy. Trastuzumab
      (Herceptin) is a recombinant monoclonal antibody against HER-2/neu, approved by
      the U.S. FDA for the treatment of patients with HER-2/neu-positive metastatic
      breast carcinomas. The results of recent studies indicate that HER-2/neu
      oncoprotein may play a role in the pathogenesis of extramammary Paget disease.
      METHODS: Using HercepTest, we analyzed HER-2/neu overexpression in seven
      noninvasive Paget lesions, two invasive lesions, and one Paget disease of the
      vulva with underlying adenocarcinoma. In addition, we investigated five mammary
      Paget diseases. RESULTS: Overexpression of HER-2/neu oncoprotein labeling
      exclusively the membranes of Paget cells was demonstrated in 8 out of 10 cases.
      One noninvasive and one with underlying adenocarcinoma stained negatively.
      Overexpression of HER-2/neu was demonstrated in all five cases of mammary Paget
      disease. CONCLUSION: Using HercepTest as a standardized detection system,
      overexpression of HER-2/neu can be demonstrated in a majority of both noninvasive
      and invasive Paget disease of the vulva. The use of Trastuzumab should be
      considered for the treatment of patients with recurrent Paget disease of the
      vulva with overexpression of HER-2/neu.

PMID- 15491755
TI  - Could precolposcopy information and counseling reduce women's anxiety and improve
      knowledge and compliance to follow-up?
AB  - OBJECTIVE: To investigate the effects of precolposcopy counseling on women's
      anxiety, knowledge about colposcopy and compliance to follow-up. METHODS: Two
      hundred and twenty women referred for colposcopy for the first time were
      recruited. They attended precolposcopy sessions in which written and video
      information were given and subsequently were randomized to have either further
      explanation and discussion with an experienced colposcopic nurse (study group) or
      no further discussion (control group). Each subject completed a Chinese version
      of the state-anxiety questionnaire (STAI) and a knowledge questionnaire before
      and immediately after the precolposcopy sessions and also before the colposcopy
      examination. Women's concern and opinion on the programme were also assessed.
      Follow-up data was compared with those who did not attend the precolposcopy
      sessions. RESULTS: Women's knowledge about colposcopy significantly improved
      after the precolposcopy sessions. The improvement was more significant in the
      study group than in the control group immediately after the sessions (P = 0.003).
      The difference between the groups in knowledge scores remained statistically
      significant before colposcopic examination (P = 0.015) but the difference
      diminished between these two assessment points. There was no statistically
      significant difference between the two groups in the anxiety scores at all
      assessment points. Women who attended the precolposcopy sessions had a
      significantly higher attendance rates and better compliance to follow-up than
      those who did not attend the sessions. CONCLUSION: Precolposcopy session with
      explanation and discussion improves women's knowledge about colposcopy, but has
      negligible effects on women's anxiety before colposcopy. Provision of written and
      video information at the precolposcopy sessions can improve compliance to follow
      up after colposcopy.

PMID- 15491756
TI  - A phase I study of ifosfamide, paclitaxel, and carboplatin in advanced and
      recurrent cervical cancer.
AB  - OBJECTIVES: To determine toxicity and establish a maximum tolerated dose of
      outpatient therapy with ifosfamide, paclitaxel, and carboplatin in women with
      advanced and recurrent cervical cancer. METHODS: Eligible patients had stage IVB,
      recurrent or persistent cervical cancer that was not amenable to curative
      treatment with surgery or radiation therapy. A dose escalation through four dose
      levels was planned. Dose limiting toxicities were defined as grade 3 or grade 4
      hematologic toxicity persistent to day 1 of the next scheduled cycle, grade 2 or
      higher central neurologic symptoms related to ifosfamide and grade 3 or grade 4
      peripheral neuropathy. RESULTS: Twelve patients, aged 29 to 71, received 64
      treatments and were evaluable for toxicity. No patient was withdrawn from the
      study due to toxicity. Two patients had received prior radiation therapy without
      chemotherapy, and seven patients had received radiation therapy with concurrent
      chemotherapy. No dose limiting toxicity occurred at dose levels 1 or 2. Three
      dose reductions occurred at dose level 3 due to neutropenia and thrombocytopenia.
      The maximum tolerated dose is ifosfamide 2 g/m(2) over 2 h, paclitaxel 175
      mg/m(2) over 1 h, and carboplatin at an AUC of 5 over 45 min. Grade 3 or grade 4
      neutropenia was seen in 11 subjects. Two patients required growth factor support.
      Grade 3 or grade 4 anemia was seen in one patient. Grade 3 or grade 4 neuropathy
      was seen in one patient. Other grade 3 or grade 4 non-hematologic toxicity
      included muscle weakness, myalgia, cough, and shortness of breath. CONCLUSIONS:
      Combination therapy with ifosfamide 2 g/m(2), paclitaxel 175 mg/m(2), carboplatin
      AUC = 5 appears to be a safe regimen for the outpatient treatment of women with
      advanced or recurrent cervical cancer and warrants phase II investigation.

PMID- 15491757
TI  - Analysis of molecular alterations in chromosome 8 associated with the development
      of uterine cervical carcinoma of Indian patients.
AB  - OBJECTIVES: We have been done the detailed deletion mapping of chromosome (chr.)
      8p21.3-23 to localize the candidate tumor suppressor gene(s) (TSGs) loci as well
      as studied the mechanism of activation of c-myc gene, located at chr.8q24.1, by
      analyzing the amplification/rearrangement/HPV integration within approximately
      580 kb of c-myc locus in uterine cervical carcinoma (CaCx) of Indian patients.
      The association between the deletions in chr.8p21.3-23 and alterations in the c
      myc locus has also been analyzed. METHODS: The deletion mapping of chr.8p21.3-23
      was done by 15 microsatellite markers and the alterations in the c-myc locus were
      analyzed by Southern hybridization using the pal-1/c-myc/mlvi-4/HPV 16/18 probes
      in seven cervical intraepithelial neoplasia (CIN) and 55 primary uterine cervical
      carcinoma. The alterations in chr.8p/q have been correlated with the different
      clinicopathological parameters. RESULTS: Three discrete minimal deleted regions
      with high frequencies of loss of heterozygosity (LOH) (37-43%) were identified in
      the chr.8p23.1-23.2 (D1), 8p23.1 (D2), and 8p 21.3-22 (D3) regions within 0.41
      4.62 Mb. The deletion in the D1 region was significantly associated with the
      deletion in the D2 region (P = 0.03), whereas the deletion in D2 was marginally
      associated with the deletion in the D3 region (P = 0.07). The alterations in the
      c-myc locus were seen in 43% of the samples. About 35% of the samples showed
      coalterations in both arms of chr.8. No significant association was observed with
      the alterations in chr.8p/q as well as with the different clinicopathological
      parameters. CONCLUSIONS: The deletions in chr.8p21.3-23 and the alterations in
      the c-myc locus are independently associated with the development of CaCx. The D1
      D3 regions in chr.8p21.3-23 could harbor candidate TSGs associated with the
      development of this tumor. The c-myc gene was activated by
      amplification/rearrangement at the pal-1/c-myc/mlvi-4 loci as well as HPV
      integration in the pal-1 locus in this tumor.

PMID- 15491758
TI  - E2 sequence variations of HPV 16 among patients with cervical neoplasia seen in
      the Indian subcontinent.
AB  - OBJECTIVES: Specific nucleotide variations in the E2 DNA sequence were looked for
      in samples with an intact human papillomavirus (HPV) 16 episomal E2 DNA. METHODS:
      Ninety-two women, 76 with invasive cervical carcinoma and 16 with cervical
      intraepithelial neoplasia (CIN) were recruited. HPV DNA typing was performed by
      polymerase chain reaction (PCR) based restriction fragment length polymorphism
      (RFLP). Intact episomal E2 DNA of HPV 16 was detected by PCR. Important
      nucleotide variations in samples with amplifiable E2 DNA were detected by RFLP.
      Nucleotide sequencing was performed on representative samples to confirm RFLP
      findings. RESULTS: A total of 89 (96.7%) women were positive for HPV DNA. Of
      these, 56 (63%) were positive for HPV 16, and of these, 38 (68%) were positive
      for intact episomal HPV 16 E2 DNA while 18 (32%) were negative. Samples with
      intact episomal HPV 16 E2 DNA sequences were grouped into four different
      digestion profiles I to IV based on RFLP patterns. Digestion patterns revealed
      absence of any sequence variations in samples with digestion profile I and
      presence of a 2983 A-G variation in those with profile II. Samples with digestion
      profiles III and IV revealed three variations in the hinge region (3516 C-A, 3538
      A-C, 3566 T-G) and two in the DNA binding domain (3684 C-A, 3694 T-A) of the E2
      sequence. Sequencing performed on representative samples confirmed RFLP findings.
      CONCLUSIONS: PCR-RFLP helped in the identification of important HPV 16 E2
      sequence variations, circumventing the need for sequencing. The presence of the
      nucleotide variations in positions that could alter the biological and
      immunological functions of the E2 protein combined with its increased occurrence
      in this study bring out the importance of these variations.

PMID- 15491759
TI  - Carboplatin hypersensitivity: a 6-h 12-step protocol effective in 35
      desensitizations in patients with gynecological malignancies and mast cell/IgE
      mediated reactions.
AB  - OBJECTIVES: The incidence of hypersensitivity reactions (HR) is increased in
      patients treated with multiple courses of carboplatin. The purposes of this
      investigation were to evaluate the effectiveness of a 12-step desensitization
      protocol and to characterize the immune mechanism of carboplatin HR. METHODS: We
      analyzed 10 consecutive patients who had documented HR to carboplatin and in whom
      continued treatment with carboplatin was considered advantageous. The patients
      were treated with carboplatin using a 6-h, 12-step desensitization protocol with
      a 30-min premedication regimen. Skin tests were performed on five patients.
      RESULTS: Ten patients successfully completed 35 planned courses of
      desensitizations to carboplatin, 31 of which were without reactions. Four
      patients had symptoms during their first (n = 3) and third (n = 1)
      desensitizations but tolerated the re-administration of infusions without further
      reactions. For subsequent courses, the protocol was modified for two patients who
      had extracutaneous symptoms during desensitization and was unchanged for the
      patient who had mild urticaria. These three patients tolerated subsequent courses
      of desensitizations without reactions. The fourth patient with symptoms during
      desensitization no longer required carboplatin due to progressive disease. Of the
      five patients who were skin tested to carboplatin, four had positive wheal and
      flare reactions. In one patient, the skin test response to carboplatin became
      negative after desensitization. CONCLUSION: The 6-h, 12-step desensitization
      protocol is safe and effective for treating patients with carboplatin HR.
      Positive skin tests to carboplatin suggest a mast cell/IgE-mediated mechanism.
      Conversion of the positive skin test to a negative response after desensitization
      supports antigen-specific mast cell desensitization.

PMID- 15491760
TI  - Factors associated with cytoreducibility among women with ovarian carcinoma.
AB  - OBJECTIVES: The aim of the current study is to investigate the clinical and
      molecular factors associated with cytoreduction among women with advanced stage
      epithelial ovarian carcinoma EOC. METHODS: Seventy-two women with FIGO stage III
      and IV EOC or primary peritoneal carcinoma (PPC) underwent similar attempt at
      surgical cytoreduction, mostly by the same surgeon. The histologic material of
      these patients was reviewed and the histologic subtype and grade were assigned.
      Immunohistochemical tests were performed for expression of molecular regulators
      of apoptosis (p53, p21, Bcl(2), Bcl(x), Bax) and chemoresistance (PGP, MRP, LRP,
      GST). The following factors were assessed for their association with complete (no
      residual tumor) and optimal (residual tumor < 1 cm) cytoreduction: type of
      carcinoma (EOC versus PPC), stage, CA-125 values, ascites, histology, tumor
      grade, and p53, p21, Bcl(2), Bcl(x), Bax, PGP, MRP, LRP, GST expression using the
      odds ratio and associated 95% confidence intervals. Significant univariate odds
      ratios were assessed jointly in a multivariate logistic regression model.
      Receiver operating characteristic curve analysis was performed to determine the
      CA-125 level with the maximal cytoreduction prognostic power. RESULTS: Twenty
      three (31.9%) women had no residual tumor, 35 (48.6%) had <or=1 cm residual tumor
      and 14 (19.4%) had residual tumor >1 cm. Factors with significant univariate
      associations with complete cytoreduction included stage, CA-125 level, ascites,
      histology, and p53. p53 expression was the only factor which remained significant
      in the multivariate analysis (odds ratio 7.2, 95% CI 1.5, 34.9). A preoperative
      CA-125 value of <or=500 IU/ml best determined complete cytoreducibility.
      CONCLUSIONS: Innate tumor characteristics determine cytoreducibility of women
      with ovarian carcinoma. Pre-operative evaluation of p53 expression may be of
      value in predicting the outcome of cytoreductive surgery in women with advanced
      stage EOC.

PMID- 15491761
TI  - Full-thickness diaphragmatic resection with simple and secure closure to
      accomplish complete cytoreductive surgery for patients with ovarian cancer.
AB  - OBJECTIVE: The diaphragm is a common site of metastasis in patients with primary
      ovarian cancer. While most diaphragmatic implants are superficial, invasive
      disease can occur. This report evaluates the use of full-thickness diaphragmatic
      resection in completely cytoreduced ovarian cancer. METHODS: A prospective record
      of all patients with ovarian cancer treated between May 1, 2002, and September
      30, 2003, was kept. Seven of the 37 patients required full-thickness
      diaphragmatic resection to achieve complete cytoreduction. The surgical technique
      and outcome as well as the clinical course and disease status were monitored.
      RESULTS: Full-thickness diaphragmatic metastases were resected and diaphragmatic
      defects were closed with #1 loop-PDS suture in a mass closure technique. In
      addition to diaphragm resections, a variety of other procedures were performed to
      achieve complete cytoreduction. Intraoperative blood loss ranged from 800 to 2500
      ml. Operating room time ranged from 3.5 to 7 h. No chest tube placements were
      required. The length of hospitalization ranged from 10 to 24 days. Paclitaxel and
      carboplatin was administered to each patient without the need for dose reductions
      or treatment delays. Complete clinical response was achieved in six of seven
      patients. One patient died with disease 4 months after surgery. Follow-up ranged
      from 4 to 21 months. CONCLUSIONS: Diaphragmatic resection is feasible and has
      minimal morbidity. The use of a loop-PDS suture to close the diaphragmatic defect
      adds ease and security to the procedure. If complete cytoreduction can be
      accomplished with the use of this procedure, it is conceivable that benefits in
      clinical outcomes may be offered to patients with aggressive, advanced ovarian
      cancer.

PMID- 15491762
TI  - Primary gastrointestinal cancers presenting as gynecologic malignancies.
AB  - OBJECTIVE: The goal of this study was to characterize presenting symptoms,
      prognostic factors, and treatment outcome in patients diagnosed with primary
      gastrointestinal (GI) cancers initially presumed to be of gynecologic origin.
      METHODS: A retrospective review of all admissions to the gynecologic oncology
      service at Saint Luke's Hospital in Kansas City, Missouri, was performed between
      1993 and 2003. Twenty-six patients with primary GI cancers who presented with
      presumed gynecologic malignancies were identified. Clinical and pathologic
      features were reviewed, methods of diagnosis were recorded, and survival was
      analyzed by the Kaplan-Meier method. RESULTS: One percent of all gynecologic
      cancer referrals had a tumor of nongynecologic gastrointestinal origin. Seven
      subtypes of GI cancers were identified, most at stage 4 disease. Colon cancer was
      identified most commonly (26.9%). Abdominal pain was the most frequent symptom
      (57.6%), and an adnexal mass was diagnosed in the majority of patients (65.4%).
      Preoperative endoscopic evaluation provided a definitive diagnosis in only 3.8%.
      The median survival was 15 months with a 5-year survival of 35%. Ninety-six
      percent of patients had their GI tumor definitively diagnosed by exploratory
      laparotomy. Optimal cytoreduction provided a 7-month survival advantage.
      CONCLUSION: Most patients required a major surgical procedure to establish the
      primary diagnosis of gastrointestinal cancer. The cancers encountered were almost
      always at advanced stage disease and were referred to the gynecologic oncologist
      due to the presence of an adnexal mass and a failed preoperative work-up.
      Surgical management should include removal of the primary or recurrent GI tumor
      and cytoreduction of all bulky disease, including adnexal metastases.

PMID- 15491763
TI  - Endometrial carcinoma recurrence in an abdominal scar 14 years after total
      hysterectomy.
AB  - BACKGROUND: Abdominal scar recurrence of endometrial carcinoma after hysterectomy
      has been only occasionally described and occurred mostly within 5 years after
      surgery. Direct tumor cell seeding in the abdominal wound at the time of
      operation is thought to be most likely the cause of recurrence. CASE: The patient
      underwent total abdominal hysterectomy for early stage endometrial carcinoma. She
      presented 14 years later with an abdominal scar recurrence that was radically
      resected. Histology of the tumor was similar to that of the primary carcinoma.
      CONCLUSION: Recurrences of endometrial carcinoma in an abdominal scar can occur
      even many years after hysterectomy and the concept of dormant cancer tumor cells
      is discussed as cause of recurrence rather than direct tumor cell implantation at
      the time of operation.

PMID- 15491764
TI  - A rare association of Sweet's syndrome with cervical cancer.
AB  - BACKGROUND: Approximately 10-20% of patients with Sweet's syndrome have an
      associated malignancy. To our knowledge, Sweet's syndrome has been reported in
      cervical cancer in only three other patients. CASE: We report a case of a 44-year
      old female diagnosed with cervical cancer (FIGO IIIB), treated with concurrent
      chemotherapy and radiation therapy. Approximately 5 months after completing
      treatment, she presented with nausea, vomiting, and bullous pustular lesions on
      the hand. She was found to have a small bowel obstruction due to recurrence of
      her cervical cancer, and a biopsy of the skin lesion showed a marked dermal
      neutrophilic infiltrate consistent with Sweet's syndrome. CONCLUSION: We report a
      case of Sweet's syndrome associated with cervical cancer, which is a rare
      finding.

PMID- 15491765
TI  - Recurrent vulvar carcinoma in pregnancy.
AB  - BACKGROUND: Vulvar carcinoma is rare in the premenopausal age group. The
      incidence during pregnancy is even more uncommon. To date, no cases of recurrent
      vulvar carcinoma in pregnancy have been reported. We describe the first case of
      recurrent vulvar carcinoma during the same pregnancy. CASE: A 36-year-old G5P4004
      presented with vulvar pain at 18 weeks of pregnancy. She had a 2.2-cm tender mass
      anterior to the left labium majus, of which a biopsy revealed invasive squamous
      cell carcinoma. At 23 weeks' gestation, she underwent a modified radical
      vulvectomy and bilateral inguinofemoral lymph node dissection. Eleven weeks
      later, she complained of a newly tender area to the right of the clitoris. A
      biopsy at that time demonstrated predominantly severe vulvar intraepithelial
      neoplasia (VIN III) with a small focus of invasive squamous cell carcinoma. A
      radical local excision was performed at 9 weeks postpartum. CONCLUSION: Careful
      surveillance is warranted as squamous cell carcinoma recurrence can occur quickly
      in the setting of pregnancy.

PMID- 15491767
TI  - Unexpected metastatic lobular carcinoma of the breast with intraabdominal spread
      and subsequent port-site metastasis after diagnostic laparoscopy for exclusion of
      ovarian cancer.
AB  - INTRODUCTION: Although lobular carcinomas metastasize primarily to lymph nodes,
      bone, lung and liver, they can also spread to the gastrointestinal tract,
      peritoneum and gynecologic organs. CASE REPORT: We report a case of
      intraperitoneal carcinomatosis of a lobular breast carcinoma that metastasized
      primarily to the peritoneum, with a subsequent abdominal wall invasion at the
      trocar site following laparoscopic surgery for the exclusion of an ovarian
      carcinoma. DISCUSSION: Port-site metastases (PSM) have occurred after
      laparoscopic surgery for endometrial, fallopian tube, ovarian, and cervical
      cancers. This is the first report of PSM of a lobular breast carcinoma primarily
      metastasized to the abdominal cavity. Every surgeon should be aware of the
      metastatic pattern of breast cancer, especially in relation to its histological
      subtypes. This case report emphasizes that PSM can occur in various kinds of
      gynecologic tumors, including breast cancer.

PMID- 15491766
TI  - Malignant female adnexal tumor of probable wolffian origin relapsing after
      pregnancy.
AB  - BACKGROUND: Female adnexal tumors of probable wolffian origin (FATWO) represent a
      rare gynecologic tumor and display in the majority of cases a benign behavior.
      CASE: A 27-year-old woman underwent a laparotomy for a left adnexal mass.
      Pathologic examination showed a FATWO. Three years later, 1 month after a vaginal
      delivery, a recurrence of the disease was observed. Immunohistochemistry revealed
      the presence of progesterone receptors that may explain recurrence after
      pregnancy. CONCLUSION: In light of this case, hormone dependency of FATWO may be
      suggested.

PMID- 15491768
TI  - Uterine adenomyoma with lymphoid infiltration simulating lymphoma.
AB  - BACKGROUND: Uterine leiomyoma with lymphoid infiltration is a rare disease that
      simulates malignant lymphoma with only nine cases reported to date. We describe
      the first case of uterine adenomyoma with lymphoid infiltration simulating
      lymphoma. CASE: The specimen resected from a 30-year-old Chinese woman was a well
      defined firm nodule measuring 5 x 5.5 x 5.5 cm. The cut surface was similar to
      that of adenomyoma, which contained dark brown spots and a cyst. Microscopically,
      the tumor comprised smooth muscle cells intermixed with many lymphocytes. Many
      lymphoid follicles were present, just locating beside one side of thin-walled
      blood vessels and protruding into the vessels. Endometrial-type glands and stroma
      were visible in the tumor. CONCLUSION: We describe the first case of uterine
      adenomyoma with lymphoid infiltration simulating lymphoma.

PMID- 15491769
TI  - The classification of a uterine sarcoma as 'high-grade endometrial stromal
      sarcoma' should be abandoned.

PMID- 15491772
TI  - Regarding "First case of a centropelvic recurrence after radical trachelectomy:
      literature review and implications for the preoperative selection of patients,"
      (92:1002-5) by Morice et al.

PMID- 15491773
TI  - Re: ERBB2 amplification is superior to protein expression status in predicting
      patient outcome in serous ovarian carcinoma (92:31-39) by Lassus et al.

PMID- 15491775
TI  - DNA methyltransferase inhibitors: old and new drugs for an epigenetic cancer
      therapy.
AB  - The pharmacological inhibition of DNA methyltransferases provides novel
      opportunities for the therapy of human cancers. Several Phase III trials of DNA
      methyltransferase inhibitors have been completed successfully, but the efficacy
      of these compounds appears to be compromised by their lack of specificity. To
      address this issue, much work has been focused on defining the functional
      characteristics of human DNA methyltransferases. This knowledge will be essential
      for the design of a new generation of pharmacological inhibitors that target
      epigenetic processes.

PMID- 15491776
TI  - Not all progestins are the same: implications for usage.
AB  - Recent clinical evidence showing unexpected side-effects of progestins used in
      contraception and hormone replacement therapy has highlighted the importance of
      choice of synthetic progestin. The molecular mechanisms of action of the
      relatively nonspecific and most widely used synthetic progestins,
      medroxyprogesterone acetate and norethisterone, are discussed in the context of
      this recent clinical evidence. Future directions involving a more mechanism-based
      approach for improved therapeutics, with greater specificity and fewer side
      effects, are discussed.

PMID- 15491777
TI  - Is JAK3 a new drug target for immunomodulation-based therapies?
AB  - JAK3, a member of the Janus kinase family, has a crucial role in T-cell
      development and the homeostasis of the immune system because of its association
      with the common gamma chain (gammac) of cytokine receptors. Disruption of either
      JAK3 or gammac expression results in severe combined immunodeficiency disease.
      Thus, JAK3 has attracted significant attention in recent years as a target for
      therapeutic intervention in several immune-related diseases. Inhibitors of JAK3
      have been developed that might act as either immunosuppressive agents in human
      organ transplantation or as immunomodulators in autoimmune disorders. We propose
      that targeting JAK3 offers alternative avenues for the development of new
      immunomodulatory strategies of therapeutic value. Furthermore, we believe that in
      addition to the tyrosine kinase domain of JAK3, where inhibitor design efforts
      are currently focused, non-catalytic regions of JAK3 might represent candidate
      targets for future drugs.

PMID- 15491778
TI  - Mast cells as targets of corticotropin-releasing factor and related peptides.
AB  - Several inflammatory skin conditions, including atopic dermatitis (AD) and
      psoriasis, are exacerbated by stress. Recent evidence suggests that crosstalk
      between mast cells, neurons and keratinocytes might be involved in such
      exacerbation. Mast cells are distributed widely in the skin, are present in
      increased numbers in AD and are located in close proximity to substance P- or
      neurotensin-containing neurons. Corticotropin-releasing factor (CRF), its
      structurally related peptide urocortin (Ucn) and their receptors are also present
      in the skin and their levels are increased following stress. Human mast cells
      synthesize and secrete both CRF and Ucn in response to immunoglobulin E receptor
      (FcepsilonRI) crosslinking. Mast cells also express CRF receptors, activation of
      which leads to the selective release of cytokines and other pro-inflammatory
      mediators. Thus, we propose that CRF receptor antagonists could be used together
      with natural molecules, such as retinol and flavonoids, to inhibit mast cell
      activation and provide new therapeutic options for chronic inflammatory
      conditions exacerbated by stress.

PMID- 15491779
TI  - The pharmacology of cough.
AB  - Cough is an indispensable defensive reflex. Although generally beneficial, cough
      is also a common symptom of diseases such as asthma, chronic obstructive
      pulmonary disease (COPD) and lung cancer. Cough remains a major unmet medical
      need and, although the centrally acting opioids have remained the antitussive
      drug of choice for decades, such opioids possess many unwanted side-effects.
      However, new research into the behaviour of airway sensory nerves has provided
      greater insight into the mechanisms of cough and new avenues for the discovery of
      novel non-opioid antitussive drugs. In this article, the pathophysiological
      mechanisms of cough and the implications of this research for the development of
      novel antitussive drugs will be discussed. A poster depicting the pharmacology of
      cough is available online and in print as to this article.

PMID- 15491780
TI  - Erythropoietin in the brain: can the promise to protect be fulfilled?
AB  - Erythropoietin (EPO) has emerged as a versatile growth factor that has
      transcended its traditional role as a mediator of erythroid maturation to one
      that modulates stem cell development, cellular protection and angiogenesis in the
      brain. As a possible candidate for nervous system disorders, it becomes crucial
      to understand the cellular mechanisms that foster cytoprotection rather than
      cytotoxicity for EPO. EPO offers novel neuronal and vascular protection not only
      through the maintenance of cellular integrity, but also through the prevention of
      cellular inflammation. The protective and anti-inflammatory capacities of EPO
      originate with the Janus tyrosine kinase 2 protein and protein kinase B (Akt).
      Downstream cellular pathways include FOXO3a, GSK-3beta, Bad, Bcl-xL, NF-kappaB,
      mitochondrial membrane permeability, APAF-1 and caspases. Further understanding
      of the cellular pathways that are susceptible to modulation by EPO will be
      crucial to foster the development of this agent as a robust and efficacious
      therapy for the brain.

PMID- 15491781
TI  - Na+ channel expression along axons in multiple sclerosis and its models.
AB  - Following the loss of myelin from axons in multiple sclerosis, some axons recover
      the ability to conduct impulses despite the absence of an insulating sheath,
      providing a basis for remission of clinical deficits. By contrast, other axons
      degenerate and contribute to non-remitting clinical deficits and, thus,
      disability. Investigations using laboratory models of multiple sclerosis indicate
      that altered expression of two distinct isoforms of Na+ channels underlies these
      two processes, and the study of human tissue reveals similar changes in multiple
      sclerosis.

PMID- 15491782
TI  - Pharmacological interventions in ventilator-induced lung injury.
AB  - During mechanical ventilation the lungs are exposed to substantial physical
      forces. This is particularly true for patients with acute lung injury, where the
      applied pressures are two to three times higher than those present during normal
      breathing. The resultant overdistension activates specific mechanotransduction
      pathways, many of which activate inflammation pathways that might lead to
      (further) acute lung injury. In this article, we review evidence suggesting that
      pharmacological strategies can interfere with ventilator-induced lung injury at
      different stages of the inflammatory cascade: blockade of transcription factors,
      neutralization of chemokines, cytokines and neuropeptides, and inhibition of
      proteases. These findings provide rationale for the use of anti-inflammatory
      therapies to treat the side-effects of mechanical ventilation.

PMID- 15491783
TI  - The TREK K2P channels and their role in general anaesthesia and neuroprotection.
AB  - Two-pore-domain K+ (K(2P)) channels are a diverse and highly regulated
      superfamily of channels that are thought to provide baseline regulation of
      membrane excitability. Of these, the TREK channels are expressed highly in the
      human CNS, and can be activated by temperature, membrane stretch and internal
      acidosis. In addition, TREK channels are sensitively activated by certain
      polyunsaturated fatty acids that have been shown to have neuroprotective activity
      and by volatile and gaseous general anaesthetics. New data derived from studies
      of knockout animals suggest that TREK-1 might have an important role in the
      general anaesthetic properties of volatile agents, such as halothane, and provide
      an explanation for the neuroprotective properties of polyunsaturated fatty acids.

PMID- 15491784
TI  - Treatment with interleukin-11 affects plasma leptin levels in inflamed and non
      inflamed rabbits.
AB  - Treatment with the anti-inflammatory cytokine, interleukin-11 (IL-11), in rabbits
      with TNBS-colitis reduces tissue damage but does not normalize body weight loss
      despite an increase in plasma levels of motilin, known to stimulate food intake.
      We investigated whether IL-11 could increase plasma levels of the anorectic
      peptide, leptin in non-inflamed and inflamed rabbits. In addition, the effect of
      IL-11 and leptin on motilin mRNA expression in the T84 cell line was tested. Five
      days post-inflammation, weight loss amounted 10.7+/-1.2%, but plasma leptin and
      motilin levels were unaffected. During IL-11 treatment, weight loss remained and
      plasma leptin levels dose-dependently increased with 27+/-5% (4 microg/kg day)
      and 108+/-7% (720 microg/kg day). Motilin levels increased in parallel with 23+/
      12% or 256+/-97%. In non-inflamed animals, a prompt decrease in weight (-11.9+/
      1%) was observed after treatment with the highest dose of IL-11 and this was
      associated with an increase in plasma leptin (70+/-18%) and motilin levels (113+/
      7%). Both IL-11 and leptin stimulated motilin mRNA expression in T84 cells with a
      different time profile. In conclusion, the increase in plasma leptin levels
      during IL-11 treatment induces wasting in normal rabbits and may be one of the
      major factors involved in the maintenance of body weight loss in rabbits with
      colitis. Increase of motilin expression by leptin may be part of a feedback
      mechanism.

PMID- 15491785
TI  - The role of arginine vasopressin in diabetes-associated increase in glucagon
      secretion.
AB  - The purpose of this study was to investigate the role of arginine vasopressin
      (AVP) on glucagon secretion in both normal and diabetic rats. Diabetes was
      induced by intravenous administration of 50 mg/kg streptozotocin, 14 days before
      pancreatic perfusion. Diabetic rats were maintained on insulin replacement
      therapy until approximately 48 h before the perfusion experiments. Both glucagon
      and AVP were determined in the effluent of the perfused pancreas using RIA. Both
      normal and diabetic rats had similar basal glucagon secretion. AVP (3-30 pM)
      increased glucagon secretion from both normal and diabetic rats in a
      concentration-dependent manner. However, diabetic subjects were more sensitive to
      AVP administration than normal subjects with regard to glucagon secretion. By
      comparison of the areas under the curves, AVP-induced glucagon secretion in
      diabetic rats was approximately 2-fold that of the normal rats. In addition,
      immunoreactive AVP was detected in the effluent of the perfused pancreas, and
      diabetic rats had 70% higher AVP concentrations in the pancreatic effluent than
      normal rats. We conclude that AVP is secreted from the pancreas and diabetic rats
      can secrete more AVP from the pancreas than normal rats. Consequently, AVP may
      have a greater impact on glucagon secretion in diabetic subjects than normal
      ones. AVP might play an important role in the hypersecretion of glucagon in
      diabetic subjects.

PMID- 15491786
TI  - Effect of nutritional rehabilitation on circulating ghrelin and growth hormone
      levels in patients with anorexia nervosa.
AB  - Circulating ghrelin and growth hormone (GH) are up-regulated in anorexia nervosa
      (AN) as a consequence of prolonged starvation. The current study examines the
      effect of nutritional rehabilitation with improvement of eating behavior on
      ghrelin and GH levels in AN patients during the course of inpatient treatment.
      The subjects included 34 female AN patients and 9 age-matched female controls.
      Fasting blood samples were collected before, during and after treatment. For data
      analysis, AN subjects were divided into three subtypes. The first group included
      seven patients with emergent hospitalization (E-AN), who were accompanied by
      severe emaciation due to their inability for food intake for more than a month.
      The other two groups included 14 AN with restricting (AN-R) and 13 AN with binge
      eating/purging (AN-BP) patients. There were significant correlations between
      ghrelin, GH and body mass index (BMI) before treatment in all subjects. However,
      ghrelin levels were not significantly correlated with BMI and GH although there
      was a relationship between GH and BMI after treatment. Before treatment, E-AN
      patients had the highest levels of ghrelin and GH with the lowest glucose levels
      and liver dysfunction. The AN-BP group had a higher level of ghrelin than the AN
      R group. During treatment, comparing with the controls group only the AN-R group
      showed higher level of ghrelin. Contrarily, the ghrelin levels in the E-AN group,
      who showed improved glucose levels, and the AN-BP group, who stopped vomiting
      behavior due to our treatment, decreased ghrelin levels. After treatment, only
      the AN-BP group showed a higher ghrelin level as compared to the controls.
      Although GH levels of the three AN groups decreased gradually according to our
      treatment progress, it still showed the higher value than the control group at
      the end of the treatment because every AN patients could not reach to more than
      80% of their ideal body weight at discharge. These findings suggest that (1)
      severe emaciation with abnormal fasting hypoglycemia in AN patients may cause
      very high levels of GH and ghrelin, (2) that GH levels in AN patients may relate
      to nutritional status and (3) that ghrelin may be influenced by not only
      nutritional status but also the eating behavior of the patients.

PMID- 15491787
TI  - Abnormalities of the hypothalamo-pituitary-thyroid axis in the pro
      opiomelanocortin deficient mouse.
AB  - The melanocortin system is an important regulator of body weight and the
      hypothalamo-pituitary-thyroid (HPT) axis. The pro-opiomelanocortin (POMC)-null
      mouse, deficient in all POMC-derived peptides, including alpha-melanocyte
      stimulating hormone (alpha-MSH), has an obese phenotype. We studied the HPT axis
      of POMC-null mice, which has not been previously investigated. Because alpha-MSH
      has a stimulatory effect on the HPT axis, we hypothesised that these mice would
      have a down-regulated thyroid axis, consistent with a recent study of POMC-null
      humans. The activity of the HPT axis was studied by collecting blood, pituitaries
      and hypothalami from ad libitum fed, adult POMC-null, heterozygous and wild-type
      mice. POMC-null mice had significantly elevated plasma total T(4) (TT(4)) and
      free T(3) (fT(3)) with reduced plasma thyroid stimulating hormone (TSH),
      pituitary TSH content and hypothalamic thyrotrophin stimulating hormone (TRH)
      content compared to wild-type mice. No significant differences between
      heterozygous and wild-type mice were observed. POMC-null mice have an abnormal
      HPT axis, which may contribute to their hyperphagia and obesity. These
      abnormalities are in contrast to those observed in POMC-null humans. These
      findings support a role for the melanocortin system in the regulation of the HPT
      axis.

PMID- 15491788
TI  - Effects of ghrelin on the proliferation and secretion of splenic T lymphocytes in
      mice.
AB  - Ghrelin, a novel gut--brain peptide predominantly produced by the stomach,
      displays strong growth hormone (GH)-releasing activity mediated by the
      hypothalamus-pituitary GH secretagogue receptor (GHS-R). Recently, the ghrelin
      receptor has also been detected in peripheral systems including immune tissues,
      suggesting that ghrelin may play an important role in the regulation of immune
      function. In this paper, we assessed the presence and function of the ghrelin
      receptor in murine splenic T cells. The enriched T cells express the mRNA of
      ghrelin and ghrelin receptor mRNA, and there is a significantly positive
      correlation between them. Moreover, we showed that ghrelin dose-dependently
      inhibits proliferation of splenic T cells when they are costimulated by anti-CD3.
      In addition, ghrelin suppressed Th(1) (IL-2 and IFN-gamma) and Th(2) (IL-4 and IL
      10) cytokines mRNA expression. These results demonstrate the presence of the
      ghrelin receptor in murine spleen T lymphocytes and a functional role of ghrelin
      as a modulator of lymphocyte function. This function of ghrelin may have some
      relevance to the pathophysiology of immunologic alterations related to
      metabolism.

PMID- 15491789
TI  - Acute insulin infusion decreases plasma ghrelin levels in uncomplicated obesity.
AB  - BACKGROUND: Plasma ghrelin levels have been shown to decrease after insulin
      infusion in lean subjects. Nevertheless, the mechanism of the suggested
      inhibitory effect of insulin on ghrelin is still unclear and no data about the
      effect of acute insulin infusion on plasma ghrelin concentration in obese
      subjects are available. OBJECTIVE: We sight to evaluate plasma ghrelin
      concentration during an hyperinsulinemic euglycemic clamp in uncomplicated obese
      subjects. METHODS: 35 uncomplicated obese subjects, body mass index (BMI) 43.3+/
      10.1 kg/m(2), 33 women and 2 men, mean age 34.9+/-10, with a history of excess
      fat of at least 10 years underwent euglycemic hyperinsulinemic clamp. Blood
      samples for ghrelin were performed at baseline and steady state of euglycemic
      insulin clamp. RESULTS: Ghrelin concentrations decreased over time to 10.6+/-15%
      (range 2-39%) of baseline, from a mean of 205.53+/-93.79 pg/ml to 179.03+/-70.43
      pg/ml during the clamp (95% CI, 10.69 to 36.44, P<0.01). In a univariate linear
      regression analysis baseline plasma ghrelin levels were inversely correlated to
      BMI (r=-0.564, P=0.04). A linear positive trend between whole body glucose
      utilization (M(FFMkg) index) and ghrelin reduction during the clamp was found
      (chi(2) 3.05, p=0.05). CONCLUSIONS: Our data seem to suggest that
      hyperinsulinemia during a euglycemic clamp is able to suppress plasma ghrelin
      concentrations in uncomplicated obesity. This effect appears to be positively
      related to insulin sensitivity.

PMID- 15491790
TI  - alpha-MSH and gamma-MSH inhibit IL-1beta induced activation of the hypothalamic
      pituitary-adrenal axis through central melanocortin receptors.
AB  - Alpha-melanocyte-stimulating hormone (alpha-MSH) is a neuroimmunomodulatory
      peptide that is involved in the control of host responses trough modulation of
      production and action of proinflammatory cytokines in inflammatory cells in the
      periphery and within the central nervous system (CNS). However, little is known
      about the receptors that mediate the modulatory effects of alpha-MSH in the CNS.
      The objective of the present study was to establish the specific melanocortin
      receptors involved in the inhibition by MSH peptides of IL-1beta-induced
      activation of the HPA. i.c.v. injection of 12.5 ng of IL-1beta caused significant
      changes in plasma corticosterone, as compared to basal levels. The treatment with
      gamma-MSH (1 microg), an MC3 receptor agonist, resulted in significant reduction
      of the IL-1beta-induced plasma corticosterone levels. Administration of the
      MC3/MC4 receptor antagonist SHU9119 blocked this effect. Besides, treatment with
      a high dose of alpha-MSH (1 microg) increased plasma corticosterone. When alpha
      MSH was given at a lower dose (0.1 microg), it did not modify corticosterone
      levels but caused an inhibitory effect on the corticosterone release induced by
      IL-1beta. The administration of SHU9119 or a more selective MC4 receptor
      antagonist like HS014 blocked the effects of alpha-MSH. In conclusion, our
      results suggest that both alpha-MSH and gamma-MSH are capable of inhibiting the
      effect of the IL-1beta on the activation of HPA axis acting at the CNS, and that
      this effect is mediated by specific central melanocortin receptors.

PMID- 15491791
TI  - Salusins promote cardiomyocyte growth but does not affect cardiac function in
      rats.
AB  - Salusin-alpha and -beta are newly found polypeptides that stimulate
      proliferation, hypotension and bradycardia in vascular smooth muscle cells
      (VSMCs) and fibroblasts. Propresalusin mRNA is widespread, and positive stains
      for salusins have been observed in many human tissues such as endothelium and
      ventricular tissue. To investigate the bio-effect of salusins on cardiovascular
      function, 20 nmol/kg salusin-alpha or 2 nmol/kg salusin-beta was intravenously
      (i.v.) injected into rats, and isolated rat hearts were perfused with 10(-12) to
      10(-7) mol/l salusin-alpha or -beta. (45)Ca(2+) uptake and (3)H-Leucine
      incorporation were determined in cultured neonatal rat cardiomyocytes. Neither
      salusin-a nor -beta affected cardiac function in vivo or in vitro but salusin
      beta decreased mean arterial blood pressure (MAP). The polypeptides' stimulation
      of (45)Ca(2+) uptake and (3)H-Leucine incorporation was concentration-dependent,
      and the incorporation was inhibited by nicardipine (Nic) and FK-506 [FK; an
      inhibitor of calcineurin (CaN)]. PD(98059) [PD; inhibitor of mitogen-activated
      protein kinase (MAPK)] and chelerythrine [inhibitor of protein kinase C (PKC)]
      inhibited salusin-stimulated (3)H-Leucine incorporation. Endothelin-1 (ET)
      synergistically increased salusin-induced (45)Ca(2+) uptake. Our results suggest
      that salusin-alpha and -beta did not directly affect cardiac function in the rat
      heart but that they improved calcium uptake and protein synthesis in neonatal rat
      cardiomyocytes through the calcium, calcineurin, MAPK and PKC signal pathways.
      Salusins may be regulatory factors for myocardial growth and hypertrophy.

PMID- 15491792
TI  - Nociceptin antagonism: probing the receptor by N-acetyl oligopeptides.
AB  - In search for effective antagonist structures for the nociceptin (NOP) receptor,
      a number of N-acylated oligopeptides, including N-acyl tetra- and pentapeptides
      selective for the kappa-opioid receptor, as well as N-acyl hexapeptides bearing
      the Ac-Arg-Tyr-Tyr-Arg-Ile-Lys (Ac-RYYRIK) core sequence originally isolated from
      combinatorial chemical libraries, were synthesized and studied in radioreceptor
      binding assays, [(35)S]GTPgammaS functional tests and in mouse vas deferens (MVD)
      bioassays. The properties of the novel antagonist candidates were compared to
      known antagonists. A new antagonist structure with a reduced, primer alcohol C
      terminus, Ac-Arg-Tyr-Tyr-Arg-Ile-lysinol (Ac-RYYRIK-ol) was described in the
      mouse vas deferens tests, showing an equilibrium inhibitory constant value (K(e))
      of 2.44 nM, and no agonist effect at 10 microM ligand concentration. Schild
      analysis indicated a clearly competitive interaction at the NOP receptor, whereas
      the peptide did not affect the action of the delta-opioid receptor agonist [D
      Ala(2),D-Leu(5)]enkephalin. Ac-RYYRIK-ol also exhibited a high affinity in
      [(3)H]nociceptin-NH(2) binding competition assays using rat brain membranes.
      Agonist-induced G-protein activation via NOP receptors was studied in
      [(35)S]GTPgammaS binding stimulation assays by the use of both native brain
      tissue preparations and membranes from cultured CHO cells expressing recombinant
      nociceptin receptors. Ac-RYYRIK-ol displayed only weak intrinsic agonist
      activity, whereas it effectively inhibited the stimulation generated by
      nociceptin. The results support the high potency and antagonist nature of Ac
      RYYRIK-ol and reveal important roles for both the N- and the C-terminal region of
      the molecule.

PMID- 15491793
TI  - Secretion of incretin hormones (GIP and GLP-1) and incretin effect after oral
      glucose in first-degree relatives of patients with type 2 diabetes.
AB  - AIMS/HYPOTHESIS: Since insulin secretion in response to exogenous gastric
      inhibitory polypeptide (GIP) is diminished not only in patients with type 2
      diabetes, but also in their normal glucose-tolerant first-degree relatives, it
      was the aim to investigate the integrity of the entero-insular axis in such
      subjects. METHODS: Sixteen first-degree relatives of patients with type 2
      diabetes (4 male, 12 female, age 50+/-12 years, BMI 26.1+/-3.8 kg/m(2)) and 10
      matched healthy controls (negative family history, 6 male, 4 female, 45+/-13
      years, 26.1+/-4.2 kg/m(2)) were examined with an oral glucose load (75 g) and an
      "isoglycaemic" intravenous glucose infusion. Blood was drawn over 240 min for
      plasma glucose (glucose oxidase), insulin, C-peptide, GIP and glucagon-like
      peptide 1 (GLP-1; specific immunoassays). RESULTS: The pattern of glucose
      concentrations could precisely be copied by the intravenous glucose infusion
      (p=0.99). Insulin secretion was stimulated significantly more by oral as compared
      to intravenous glucose in both groups (p<0.0001). The percent contribution of the
      incretin effect was similar in both groups (C-peptide: 61.9+/-5.4 vs. 64.4+/
      5.8%; p=0.77; insulin: 74.2+/-3.3 vs. 75.8+/-4.9; p=0.97; in first-degree
      relatives and controls, respectively). The individual responses of GIP and GLP-1
      secretion were significantly correlated with each other (p=0.0003). The
      individual secretion of both GIP and GLP-1 was identified as a strong predictor
      of the integrated incremental insulin secretory responses as well as of the
      incretin effect. CONCLUSION/INTERPRETATION: Despite a lower insulin secretory
      response to exogenous GIP, incretin effects are similar in first-degree relatives
      of patients with type 2 diabetes and control subjects. This may be the result of
      a B cell secretory defect that affects stimulation by oral and intravenous
      glucose to a similar degree. Nevertheless, endogenous secretion of GIP and GLP-1
      is a major determinant of insulin secretion after oral glucose.

PMID- 15491794
TI  - Antigen-based immunointervention in human autoimmune diseases.
AB  - Antigen administration can ameliorate autoimmune disease via various mechanisms,
      including deletion of autoreactive cells, induction of regulatory T cells, and
      deviation to non-pathogenic or protective responses. All these mechanisms of
      immunointervention have been successfully used to prevent and sometimes treat
      experimental models of autoimmune diseases. Based on these results, expectations
      have been raised for exploiting similar strategies to inhibit pathogenic
      autoreactive T cells in human autoimmune diseases. Among them, mucosal
      administration of autoantigen is an attractive mode of immunointervention still
      awaiting demonstration of clinical efficacy in human autoimmune diseases. A
      further step in this direction is now provided by the clear-cut immune deviation
      observed following oral administration of a disease-related peptide to rheumatoid
      arthritis patients, leading to inhibition of Th1 while enhancing Th2 and possibly
      Foxp3-positive regulatory T cells.

PMID- 15491796
TI  - GenCompass: a universal system for analysing gene expression for any genome.
AB  - Microarrays have become indispensable tools for studying the gene expression of
      particular organisms on a genomic scale. However, despite its widespread use,
      there are several draw-backs to the current technology. First, it requires prior
      knowledge of the DNA sequence encoded in the organism of interest, and second,
      chips must be designed specifically for each genome, greatly increasing the
      initial cost incurred in manufacturing the arrays.

PMID- 15491795
TI  - Replication vehicles of protein-based inheritance.
AB  - Prions are self-perpetuating protein isoforms that are responsible for infectious
      diseases in mammals and for heritable traits in fungi. Most known prion proteins
      form amyloids--self-seeded fiber-like aggregates. Prion propagation
      ('replication') could be described as a sequence of repetitive cycles of
      aggregate 'shearing' into smaller seeds followed by the growth of these seeds
      into full-size polymers. Recent work shows that the ability to form aggregates
      and to propagate them is controlled by distinct regions of the composite prion
      domains (PrDs).

PMID- 15491797
TI  - Rewiring the cell: synthetic biology moves towards higher functional complexity.
AB  - A steady stream of research has fueled excitement in the field of synthetic
      biology. Logic gates, oscillators, and memory elements constructed using genetic
      and biochemical components have all been demonstrated. However, the nagging
      question remains as to how higher levels of complexity can be designed into these
      synthetic systems. A recent paper from Collins' group provides some answers to
      this question.

PMID- 15491798
TI  - Can heterologous gene expression shed (a torch) light on protein function?

PMID- 15491799
TI  - Gene therapy in the clinic: whose risks?
AB  - Current experience with gene therapy for X-linked severe combined
      immunodeficiency disorder (X-SCID) suggests that we might now be at the point
      where it can be considered the 'standard of care'. This therapy carries an
      unquantified risk of leukaemia, raising important questions for regulators. How
      dangerous does a potentially curative therapy for a fatal illness need to be
      before we call it unsafe. How uncertain does a risk need to be for us to regard a
      therapy as still 'experimental'? Whose interests should prevail? Here I argue
      that in X-SCID it is the parents and children whom we should listen to first and
      foremost. How far does this patient-centred approach to licensing therapies
      extend? Can it be given a rational basis?

PMID- 15491800
TI  - The myth of the biotech revolution.
AB  - The existence of a medicinal 'biotech revolution' has been widely accepted and
      promoted by academics, consultants, industry and government. This has generated
      expectations about significant improvements in the drug discovery process,
      healthcare and economic development that influence a considerable amount of
      policy-making. Here we present empirical evidence, from a variety of indicators,
      that shows that a range of outputs have failed to keep pace with increased
      research and development spending. Rather than producing revolutionary changes,
      medicinal biotechnology is following a well-established pattern of slow and
      incremental technology diffusion. Consequently, many expectations are wildly
      optimistic and over-estimate the speed and extent of the impact of biotechnology,
      suggesting that the assumptions underpinning much contemporary policymaking need
      to be rethought.

PMID- 15491801
TI  - Ribosomal antibiotics: structural basis for resistance, synergism and
      selectivity.
AB  - Various antibiotics bind to ribosomes at functionally relevant locations such as
      the peptidyl-transferase center (PTC) and the exit tunnel for nascent proteins.
      High-resolution structures of antibiotics bound to ribosomal particles from a
      eubacterium that is similar to pathogens and an archaeon that shares properties
      with eukaryotes are deciphering subtle differences in these highly conserved
      locations that lead to drug selectivity and thereby facilitate clinical usage.
      These structures also show that members of antibiotic families with structural
      differences might bind to specific ribosomal pockets in different modes dominated
      by their chemical properties. Similarly, the chemical properties of drugs might
      govern variations in the nature of seemingly identical mechanisms of drug
      resistance. The observed variability in binding modes justifies expectations for
      structural design of improved antibiotic properties.

PMID- 15491802
TI  - Lessons from seashells: silica mineralization via protein templating.
AB  - Silica, the most abundant compound in the earth's crust, is also widespread in
      biological systems. Silica has many functions, including support and protection
      in single-celled organisms and in higher plants and animals alike. Despite this
      widespread occurrence and importance of function, little is known about biosilica
      and the mechanisms that produce controlled microscopic and macroscopic silica
      structures with nanoscale precision, exceeding present synthetic technological
      approaches. Here we highlight recent progress in identifying proteins, genes and
      the various environmental factors responsible for the controlled synthesis of
      silica by marine organisms. Examples of biomimetic approaches to biosilica
      formation using model peptides to control the formation of structures through
      manipulation of the processing environment are discussed.

PMID- 15491803
TI  - Non-viral vectors in cystic fibrosis gene therapy: progress and challenges.
AB  - Although the viability of cystic fibrosis (CF) gene transfer to airway epithelium
      has been demonstrated in vitro and in animal models, so far none of the clinical
      investigations using adenovirus, adeno-associated virus, lentivirus, cationic
      lipids or polymers has shown a persistent correction of the ion transport defects
      that occur in CF. Despite disappointing results, these studies have shown that
      non-viral vectors could represent a viable alternative for gene therapy in CF
      airway epithelium. The transfer efficiency of non-viral vectors is currently low,
      however, and thus these systems are not clinically relevant as yet. Before
      clinical application, several limitations encountered by non-viral delivery
      systems must be addressed. Recent progress has been made towards overcoming these
      limitations and towards making non-viral gene therapy a more realistic option for
      CF.

PMID- 15491804
TI  - Biofabrication: using biological materials and biocatalysts to construct
      nanostructured assemblies.
AB  - Emerging opportunities are placing greater demands on device fabrication: next
      generation microelectronics will need minimum features of less than 100 nm, high
      throughput drug screening will require facile methods to incorporate sensitive
      biological components into microelectromechanical systems (MEMS), and implantable
      devices will need to be built from biocompatible materials. Increasingly, these
      emerging demands are being addressed by combining traditional microfabrication
      methods with 'biofabrication': namely, the use of biologically derived materials
      and biocatalysts. Recent fabrication techniques are using biological construction
      materials as process aids or structural components, and enzymes are being
      considered for their potential to fabricate devices with high selectivity under
      mild conditions. If incompatibilities between biology and microfabrication can be
      eliminated, then biofabrication will be poised to emerge as the standard for
      nanoscale construction.

PMID- 15491806
TI  - Editorial.

PMID- 15491805
TI  - Proteomics of the Drosophila immune response.
AB  - Completion of the Drosophila genome has enabled the use of proteomic approaches
      for studying complex processes such as the innate immune defense against
      microorganisms. Microbial infection leads to the activation of responses
      involving changes at translational and post-translational levels. Proteomics is a
      tool for assessing such changes in protein expression, localization and post
      translational modification. Recently, several studies have reported whole-genome
      analyses of the Drosophila immune response, both at the transcriptome and
      proteome levels, leading to a more comprehensive view of fly immunity. In this
      review, we describe and compare the proteomic techniques used in these analyses
      and discuss the results obtained by differential protein profiling of the
      Drosophila immune response.

PMID- 15491807
TI  - Recent advances on chitosan-based micro- and nanoparticles in drug delivery.
AB  - Considerable research efforts have been directed towards developing safe and
      efficient chitosan-based particulate drug delivery systems. The present review
      outlines the major new findings on the pharmaceutical applications of chitosan
      based micro/nanoparticulate drug delivery systems published over the past decade.
      Methods of their preparation, drug loading, release characteristics, and
      applications are covered. Chemically modified chitosan or its derivatives used in
      drug delivery research are discussed critically to evaluate the usefulness of
      these systems in delivering the bioactive molecules. From a literature survey, it
      is realized that research activities on chitosan micro/nanoparticulate systems
      containing various drugs for different therapeutic applications have increased at
      the rapid rate. Hence, the present review is timely.

PMID- 15491808
TI  - Negative preclinical results with stealth nanospheres-encapsulated Doxorubicin in
      an orthotopic murine brain tumor model.
AB  - Previous results have shown that PEG-coated poly(hexadecylcyanoacrylate) (PEG
      PHDCA) nanospheres displayed a significant accumulation within an orthotopic 9L
      gliosarcoma model, after i.v. administration to rats. Hence, the aim of the
      present study was to evaluate in the same model the pre-clinical efficacy of this
      carrier when loaded with Doxorubicin, an anticancer drug which poorly distributes
      in the CNS. Free and nanospheres-encapsulated Doxorubicin were administered with
      a multiple dose treatment. Their maximum tolerated dose (MTD) and increase in
      life span were respectively assessed in healthy and intracranially 9L-bearing
      rats. A comparative biodistribution study of Doxorubicin-loaded and unloaded PEG
      PHDCA nanospheres was also performed in the tumor-bearing group. The results
      showed that the cumulative MTD of nanoparticulate doxorubicin was 1.5 times
      higher than this of free Doxorubicin. Nevertheless, encapsulated Doxorubicin was
      unable to elicit a better therapeutic response in the 9L gliosarcoma.
      Biodistribution study revealed that the Doxorubicin-loaded nanospheres
      accumulated to a 2.5-fold lesser extent in the 9L tumor as compared to the
      unloaded nanospheres and that they were mainly localized in the lungs and the
      spleen. Such a typical profile indicated aggregation with plasma proteins as a
      consequence of the positive surface charge of these loaded particles; this ionic
      interaction resulting from drug encapsulation was mainly responsible for 9L
      treatment failure.

PMID- 15491809
TI  - Anti-neovascular therapy by use of tumor neovasculature-targeted long-circulating
      liposome.
AB  - For the purpose of cancer anti-neovascular therapy (ANET), we previously isolated
      5-mer peptide Ala-Pro-Arg-Pro-Gly (APRPG) that specifically bound to the tumor
      angiogenic site and observed that APRPG-modified liposomes encapsulating
      adriamycin were effective for the suppression of tumor in tumor-bearing mice.
      Since polyethylene glycol (PEG) modification of liposomes endows them with a
      future of long circulation, we modified liposomes with PEG and APRPG-conjugated
      distearoylphosphatidylethanolamine (DSPE-PEG-APRPG) and examined the
      applicability of the liposomes on ANET. Liposomes containing DSPE-PEG-APRPG not
      only specifically bound to vascular endothelial growth factor-stimulated human
      umbilical vein endothelial cells in vitro, but also showed long-circulating
      characteristic and enhanced accumulation in tumor in vivo. Furthermore,
      adriamycin-encapsulated liposomes modified with APRPG-PEG caused more efficient
      tumor growth suppression than adriamycin-encapsulated liposomes modified with PEG
      alone in Colon 26 NL-17 carcinoma-bearing mice, despite not so much different
      accumulation of both liposomes in the tumor. These data suggest that tumor
      neovasculature-targeted long-circulating liposomes encapsulating anti-cancer
      drugs effectively eradicate cancerous cells through damaging of angiogenic
      endothelial cells. ANET promises no drug resistance and is expected to be
      effective against essentially any kind of solid tumors. The present results
      demonstrate the beneficial usage of APRPG-PEG for the active-targeting of drug
      carriers to angiogenic site in the novel modality of tumor treatment, namely
      ANET.

PMID- 15491810
TI  - Altered chemical and biological activities of all-trans retinoic acid
      incorporated in solid lipid nanoparticle powders.
AB  - The principal aim of this study was to investigate whether the solid lipid
      nanoparticle (SLN) powder formulation of all-trans retinoic acid (ATRA) can
      favorably alter the chemical stability and biological activities of ATRA. SLN
      powder formulation of ATRA was obtained by freeze-drying of SLN dispersions. The
      chemical stability of ATRA was determined by HPLC analysis. The anticancer
      efficacy of ATRA was determined by evaluating antiproliferative effects of ATRA
      on cancer cell lines. Hemolytic potential of ATRA was spectrophotometrically
      determined after incubation with red blood cells (RBCs) in vitro. ATRA could be
      efficiently incorporated in SLN powder without impairing the physical stability
      of lipid nanoparticles. After 3 months of storage, >90% ATRA remained intact in
      SLN powder, indicating that the chemical stability of ATRA was substantially
      improved by incorporation in SLN powder. The antiproliferative effects of SLN
      powder formulation of ATRA on a wide range of cancer cell lines were not
      significantly different from that of free ATRA. Furthermore, the incorporation of
      ATRA in SLN powder significantly reduced the hemolytic potential of ATRA. Taken
      together, the molecular characteristics that currently appear to limit the
      clinical efficacy of ATRA were greatly improved by preparing SLN powder
      formulation. SLN powder formulation of ATRA may have a potential in enhancing the
      efficacy of ATRA in cancer chemoprevention and therapeutics.

PMID- 15491811
TI  - Development of implant tablet for a week-long sustained release.
AB  - An implant tablet for a week-long sustained release was developed by the direct
      compression method using poly-DL-lactic acid (PLA) and poly(DL-lactic acid-co
      glycolic acid) copolymer (PLGA) as a matrix and phenol red (PR) as a model drug.
      The in vitro release was affected by formulations, especially by drug content and
      polymer species. The release rate correlated with the rate of absorption of
      water. The implant tablet (30 mg) containing 1 mg of PR, prepared using PLGA (MW
      10,000; lactic acid/glycolic acid=1:1, mol/mol) by compression at 50 kg/cm(2) for
      10 s, was found to efficiently exhibit a week-long sustained release in vitro,
      and applied in vivo. The remaining amount or plasma concentration of PR after
      s.c. administration of the implant tablet to rats demonstrated that the implant
      tablet showed a week-long sustained release in vivo. The present implant tablet
      is suggested to be useful as a drug delivery system for supplying drugs for
      approximately 1 week.

PMID- 15491812
TI  - Transdermal delivery of macromolecules by erbium:YAG laser.
AB  - The aim of this study was to assess the effect of molecular weight (MW) on the
      transdermal delivery of macromolecules by erbium:yttrium-aluminum-garnet (Er:YAG)
      laser treatment. Fluorescein isothiocyanate (FITC)-labeled dextran (FD) of
      increasing MWs (4.4, 19.4, 38, and 77 kDa) was used as the model macromolecules
      to investigate the skin permeation in vitro. Fluorescence microscopy and scanning
      electron microscopic (SEM) images were utilized to examine the transport
      mechanisms of the macromolecules via the skin after laser treatment. The results
      indicate a significant increase in the permeation of FITC and FD across skin
      treated by the laser. The MWs of macromolecules and laser fluences were found to
      play important roles in controlling macromolecular absorption. Transdermal
      delivery of FD with a MW of at least 77 kDa could be achieved with laser
      treatment. Follicular routes were significant for FITC permeation, whereas
      intercellular pathways played important roles on the delivery of FD. Ablation of
      the stratum corneum (SC) layer, photomechanical stress on intercellular regions,
      and alterations of the morphology and arrangement of corneocytes are possible
      mechanisms of how the Er:YAG laser promotes macromolecular delivery. No
      alteration of viable skin morphology was observed after laser treatment and the
      partly ablation of the SC may be reversible. Hexameric insulin showed higher skin
      permeation than did FD with similar MWs (38 kDa) with laser enhancement. From the
      study presented herein, it is concluded that the Er:YAG laser can be effective
      for transdermal delivery of macromolecules and hydrophilic permeants such as
      peptides and protein-based drugs.

PMID- 15491813
TI  - Nasal delivery of human growth hormone: in vitro and in vivo evaluation of a
      thiomer/glutathione microparticulate delivery system.
AB  - It was the aim of this study to develop and evaluate a nasal microparticulate
      delivery system for human growth hormone (hGH) based on the thiomer polycarbophil
      cysteine (PCP-Cys) in combination with the permeation mediator glutathione (GSH).
      Microparticles were prepared by dissolving PCP-Cys/GSH/hGH (7.5:1:1.5), PCP/hGH
      (8.5:1.5), and mannitol/hGH (8.5:1.5) in demineralized water, followed by
      lyophilization and micronization. Particles were evaluated with regard to size
      distribution and swelling behavior using a laser diffraction particle size
      analyzer. The release of fluorescence-labelled hGH from microparticles was
      determined in Franz diffusion chambers. In vivo studies in rats were performed
      comparing the nasal bioavailability achieved by PCP-Cys/GSH/hGH microparticles
      with that of unmodified PCP/hGH microparticles and mannitol/hGH powder. PCP
      Cys/GSH/hGH and PCP/hGH microparticles showed a comparable size distribution (80%
      in the range of 4.8-23 microm) and swelled to almost fourfold size in phosphate
      buffered saline (PBS). Both formulations exhibited almost identical sustained
      drug release profiles. The intranasal administration of the PCP-Cys/GSH/hGH
      microparticulate formulation resulted in a relative bioavailability of 8.11+/
      2.15%, which represents a 3-fold and 3.3-fold improvement compared to that of
      PCP/hGH microparticles and mannitol/hGH powder, respectively. The study suggests
      that the PCP-Cys/GSH/hGH nasal microparticulate formulation might represent a
      promising novel tool for the systemic delivery of hGH.

PMID- 15491814
TI  - Encapsulation, stabilization, and release of BSA-FITC from polyanhydride
      microspheres.
AB  - In order to determine the efficacy of using polyanhydrides as a carrier for
      therapeutic proteins, the model protein bovine serum albumin labeled with
      fluorescein isothiocyanate (BSA-FITC) was encapsulated in microspheres of poly
      sebacic anhydride (poly(SA)), and random copolymers of poly(SA) and poly(1,6-bis
      p-carboxyphenoxy)hexane (poly(CPH)). The microspheres were fabricated via the
      double emulsion (water/oil/water) technique and were characterized using scanning
      electron microscopy, gel permeation chromatography, confocal microscopy, and a
      Coulter counter. The effect of protein loading, protein distribution, and change
      in polymer composition was examined in an in vitro release study. The secondary
      structure of the encapsulated BSA-FITC was determined with Fourier transform
      infrared spectroscopy. The primary structure of the released protein was analyzed
      using sodium dodecyl sulfate polyacrylamide gel electrophoresis. Poly(SA) and
      20:80 (CPH:SA) microspheres were found to conserve the primary structure of the
      released protein and the secondary structure of the encapsulated protein, and
      showed a sustained delivery for approximately 15 and 30 days, respectively. As
      the CPH content in the copolymer increased, the secondary structure of FITC-BSA
      was not conserved, as indicated by the steep decrease in the alpha-helix content.

PMID- 15491815
TI  - Prolonged circulation of large polymeric nanoparticles by non-covalent adsorption
      on erythrocytes.
AB  - Polymeric nanoparticles have been extensively studied for use as intravascular
      drug delivery vehicles; however, their applications are limited by rapid
      clearance from circulation by the reticuloendothelial system (RES). Previous
      attempts to improve vascular circulation have focused on surface modification
      using polymers such as poloxamines, poloxamers, and polyethylene glycol, to
      prevent opsononization. We report on a novel method of prolonging intravascular
      particle circulation by anchoring the nanoparticles to the surface of red blood
      cells (RBCs). We hypothesize that particles adhered to RBCs can escape RES
      clearance due to the ability of RBCs to do so. This method is motivated by the
      strategy adopted by certain bacteria, for example, hemobartonella, that adhere to
      RBCs and remain in circulation for several weeks. Prolonged circulation of
      nanoparticles as large as 450 nm was observed after adsorption on RBCs. Although
      particles were eventually eliminated from circulation, RBCs were not cleared. RBC
      anchored nanoparticles offer a novel approach for intravascular drug delivery and
      blood pool imaging.

PMID- 15491816
TI  - A new approach to the in vivo and in vitro investigation of drug release from
      locoregionally delivered microspheres.
AB  - The purpose of this work was to determine the in vivo release profile of
      doxorubicin (Dox) delivered locoregionally by dextran-based microspheres (MS) and
      to develop an in vitro method for predicting in vivo drug release from MS-- in
      vitro-in vivo correlation (IVIVC). For the determination of in vivo Dox release,
      drug-loaded MS were placed into hollow fibers (HF) and implanted subcutaneously
      into C3H mice. Samples were retrieved at various times following implantation, MS
      removed from HF, and the amount of Dox remaining determined via
      ultraviolet/visible (UV/Vis) spectrophotometry. Various in vitro systems were
      designed and investigated for their ability to link in vivo and in vitro release
      profiles, including an open system (e.g. a column) with continuous flow of
      release medium at different flow rates and closed systems (e.g. a cuvette) using
      different release media and conditions. About 34% of loaded Dox was released from
      MS in vivo at 48 h. Only an incremental release was observed over the ensuing 72
      h. The release kinetics of Dox from MS using three of the investigated in vitro
      systems, column system and HF immersed in a buffer solution or growth medium gave
      release profiles that were highly correlated with the in vivo release profile
      (r(2)>0.9). The relationships, both linear and non-linear, suggest that Level A
      IVIVC models can be developed for Dox release from locoregionally delivered MS
      using specially designed release systems.

PMID- 15491817
TI  - Tumor-targeted liposomes: doxorubicin-loaded long-circulating liposomes modified
      with anti-cancer antibody.
AB  - Commercially available doxorubicin-loaded long-circulating liposomes (Doxil, Alza
      Pharmaceuticals) were modified with the monoclonal nucleosome (NS)-specific 2C5
      antibody (mAb 2C5) that recognizes a broad variety of tumors via the tumor cell
      surface-bound NSs. For incorporation into liposomes, mAb 2C5 was modified with
      poly(ethylene glycol)-phosphatidyl ethanolamine conjugate (PEG-PE) with the free
      PEG terminus activated with the p-nitrophenylcarbonyl group (pNP-PEG-PE).
      Derivatives of mAb 2C5 containing a variable number of PEG-PE residues (10-32)
      per protein molecule were prepared with a reasonably good preservation of the
      antibody specific activity even at the highest degree of modification. PEG-PE
      modified antibody quantitatively incorporated into the liposomal membrane of
      doxorubicin-loaded liposomes with a loss of not more than 20% of the encapsulated
      doxorubicin. 2C5-targeted Doxil liposomes acquired the ability to recognize NSs
      and specifically bind to various tumor cells. Doxorubicin-loaded long-circulating
      liposomes modified with the mAb 2C5 kill various tumor cells in vitro with the
      efficiency higher than non-targeted doxorubicin-loaded liposomes.

PMID- 15491818
TI  - Cationic submicron emulsions for pulmonary DNA immunization.
AB  - Pulmonary immunization against inhaled pathogens such as Mycobacterium
      tuberculosis would induce local and systemic immune responses and protect from
      entry and dissemination of the pathogen. The aim of this study was to evaluate
      cationic submicron emulsion as a potential carrier for DNA vaccines to the lung.
      DNA loaded emulsions were 128-152 nm in size and retained positive zeta potential
      above +40 mV during 3 months of storage. Loading efficiency was above 99%, DNA
      was protected from DNase I degradation up to 60 min and was stable in presence of
      75% fetal calf serum (FCS). The plasmid DNA was detected in the endo-lysosomal
      compartment of the human bronchial cell line, Calu-3, 6 h after application. No
      cytotoxic effect on these cells was observed. Human dendritic cells were matured
      in presence of DNA loaded emulsion, although to a lesser extent than DNA solution
      indicating slower release and lower exposure to unmethylated CpG sequences. These
      results indicate that cationic submicron emulsions are potential DNA vaccine
      carriers to the lung since they are able to transfect pulmonary epithelial cells,
      which possibly induce cross priming of antigen presenting cells and directly
      activate dendritic cells, resulting in stimulation of antigen specific T-cells.

PMID- 15491819
TI  - A review of some fish nutrition methodologies.
AB  - Several classical warm blooded animal (poultry, sheep, cows, etc.) methods for
      dietary nutrients evaluation (digestibility, metabolizablity, and energy budget)
      are applied to fish, even though fish live in a different environment in addition
      to being cold blooded animals. These applications have caused significant errors
      that have made these methods non-additive and meaningless, as is explained in the
      text. In other words, dietary digestion and absorption could not adequately be
      measured due to the aquatic environment fish live in. Therefore, net nutrient
      deposition and/or growth are the only accurate measurement left to evaluate
      dietary nutrients intake in fish. In order to understand and predict dietary
      nutrient intake-growth response relationship, several mathematical models; (1)
      the simple linear equation, (2) the logarithmic equation, and (3) the quadratic
      equation are generally used. These models however, do not describe a full range
      of growth and have no biological meaning as explained in the text. On the other
      hand, a model called the saturation kinetic model. It has biological basis (the
      law of mass action and the enzyme kinetic) and it describes the full range of
      growth curve. Additionally, it has four parameters that summarize the growth
      curve and could also be used in comparing diets or nutrients effect on fish
      growth and/or net nutrient deposition. The saturation kinetic model is proposed
      to be adequate for dietary nutrient evaluation for fish. The theoretical
      derivation of this model is illustrated in the text.

PMID- 15491820
TI  - Human excreta for plant production.
AB  - Human excreta are a natural resource which is always available in all societies.
      Unfortunately, their value is highly underestimated in present agriculture and
      horticulture including in many tropical developing countries. Especially human
      urine is rich in nitrogen. This "free" fertiliser should be used as much as
      possible and needed. In many cases, human urine and composted human faeces could
      be fortified with wood ash and kitchen and garden waste to meet the potassium and
      phosphorus needs of plants and to improve soil structure. Avoiding health risks
      and dosage requirements are also discussed. The ideas presented here can be used
      even with the cheap pit latrines that are common in the rural and peri-urban
      areas of developing countries. They do not require electricity and/or tap water.
      They may also fit conditions in areas of Eastern Europe where piped water and
      sewerage are absent and/or people lack money for fertilisers and maintenance of
      wastewater treatment plants.

PMID- 15491821
TI  - Suitability of aquaculture effluent solids mixed with cardboard as a feedstock
      for vermicomposting.
AB  - Recirculating aquaculture systems are highly intensive culture systems that
      actively filter and reuse water, thus minimizing water requirements and creating
      relatively small volumes of concentrated waste (compared to flow-through
      aquaculture systems). Vermicomposting, which uses earthworms to stabilize and
      transform organic wastes into valuable end-products, has been proposed as an
      alternative treatment technology for high-moisture-content organic wastes from
      agricultural, industrial and municipal sources. This study was conducted to
      determine if the effluent solids from a large recirculating aquaculture facility
      (Blue Ridge Aquaculture, Martinsville, Virginia) were suitable for
      vermicomposting using the earthworm Eisenia fetida. In two separate experiments,
      worms were fed mixtures of solids removed from aquaculture effluent (sludge) and
      shredded. Mixtures containing 0%, 5%, 10%, 15%, 20%, 25%, and 50% aquaculture
      sludge (dry weight basis) were fed to the worms over a 12-week period and their
      growth (biomass) was measured. Worm mortality, which occurred only in the first
      experiment, was not influenced by feedstock sludge concentration. In both
      experiments worm growth rates tended to increase with increasing sludge
      concentration, with the highest growth rate occurring with feedstocks containing
      50% aquaculture sludge. Effluent solids from recirculating aquaculture systems
      mixed with shredded cardboard appear to be suitable feedstocks for
      vermicomposting.

PMID- 15491822
TI  - High-nitrogen compost as a medium for organic container-grown crops.
AB  - Compost was tested as a medium for organic container-grown crops. Nitrogen (N)
      loss during composting of separated cow manure (SCM) was minimized using high C/N
      (wheat straw, WS; grape marc, GM) or a slightly acidic (orange peels, OP)
      additives. N conservation values in the resultant composts were 82%, 95% and 98%
      for GM-SCM, OP-SCM and WS-SCM, respectively. Physical characteristics of the
      composts were compatible with use as growing media. The nutritional contribution
      of the composts was assessed using cherry tomato (Lycopersicon esculantum Mill.)
      and by means of incubation experiments. Media were either unfertilized or
      fertilized with guano (sea-bird manure). Plant responses suggest that N
      availability is the main variable affecting growth. Unfertilized OP-SCM and WS
      SCM supplied the N needed for at least 4 months of plant growth. Root-galling
      index (GI) of tomato roots and number of eggs of the nematode Meloidogyne
      javanica were reduced by the composts, with the highest reduction obtained by OP
      SCM and WS-SCM, at 50% concentrations. These composts, but not peat, reduced the
      incidence of crown and root-rot disease in tomato as well as the population size
      of the causal pathogen, Fusarium oxysporum f. sp. radicis-lycopersici.

PMID- 15491823
TI  - Physical factors affecting the production of organic solvent-tolerant protease by
      Pseudomonas aeruginosa strain K.
AB  - The physical factors affecting the production of an organic solvent-tolerant
      protease from Pseudomonas aeruginosa strain K was investigated. Growth and
      protease production were detected from 37 to 45 degrees C with 37 degrees C being
      the optimum temperature for P. aeruginosa. Maximum enzyme activity was achieved
      at static conditions with 4.0% (v/v) inoculum. Shifting the culture from
      stationary to shaking condition decreased the protease production (6.0-10.0%
      v/v). Extracellular organic solvent-tolerant protease was detected over a broad
      pH range from 6.0 to 9.0. However, the highest yield of protease was observed at
      pH 7.0. Neutral media increased the protease production compared to acidic or
      alkaline media.

PMID- 15491824
TI  - Co-composting of filter cake and bagasse; by-products from a sugar mill.
AB  - Thailand has nearly 2 million tonnes of filter cake waste containing 1.8% total N
      from the sugar cane industry to dispose of annually. Compost studies were
      conducted to determine how rapidly this material can be converted to a stable
      product that may be useful in crop production, and to characterize the N
      transformations. Two kinds of sugar mill by-products were composted, filter cake
      and filter cake mixed with bagasse, at a 2:1 ratio to reduce the C:N ratio in an
      attempt to reduce N loss during composting. Materials were mixed manually at 3-5
      day intervals during the composting process. Both composts were analyzed at least
      weekly to measure temperature, pH, NH4+, NO3-, total N content, C loss, and
      germination index. For both mixtures, the thermophilic stage lasted 15-20 days
      and was higher than ambient for nearly 80 days. The degradation of organic matter
      (OM) was rapid in both mixtures to approximately 40 days, after which it began to
      stabilize. Both mixtures achieved maturity at approximately 90 days as indicated
      by a stable C/N, low NH4+/NO3-, lack of heat production and a germination index
      higher than 80%. Mixing filter cake with bagasse helped conserve N during
      composting. Because N was in excess, approximately 12-15% was lost from the
      composts. Mixing more bagasse with the filter cake may result in further
      reduction in N losses. Both composts have potential for use in crop production.

PMID- 15491825
TI  - Adsorption behaviour of Fe(II) and Fe(III) ions in aqueous solution on chitosan
      and cross-linked chitosan beads.
AB  - A batch adsorption system was applied to study the adsorption of Fe(II) and
      Fe(III) ions from aqueous solution by chitosan and cross-linked chitosan beads.
      The adsorption capacities and rates of Fe(II) and Fe(III) ions onto chitosan and
      cross-linked chitosan beads were evaluated. Chitosan beads were cross-linked with
      glutaraldehyde (GLA), epichlorohydrin (ECH) and ethylene glycol diglycidyl ether
      (EGDE) in order to enhance the chemical resistance and mechanical strength of
      chitosan beads. Experiments were carried out as function of pH, agitation period,
      agitation rate and concentration of Fe(II) and Fe(III) ions. Langmuir and
      Freundlich adsorption models were applied to describe the isotherms and isotherm
      constants. Equilibrium data agreed very well with the Langmuir model. The kinetic
      experimental data correlated well with the second-order kinetic model, indicating
      that the chemical sorption was the rate-limiting step. Results also showed that
      chitosan and cross-linked chitosan beads were favourable adsorbers.

PMID- 15491826
TI  - Recycling of manure nutrients: use of algal biomass from dairy manure treatment
      as a slow release fertilizer.
AB  - An alternative to land spreading of manure is to grow crops of algae on the N and
      P present in the manure and convert manure N and P into algal biomass. The
      objective of this study was to evaluate the fertilizer value of dried algal
      biomass that had been grown using anaerobically digested dairy manure. Results
      from a flask study using two soils amended with algal biomass showed that 3% of
      total algal nitrogen (N) was present as plant available N at day 0. Approximately
      33% of algal N was converted to plant available N within 21 days at 25 degrees C
      in both soils. Levels of Mehlich-3 extractable phosphorus (P) in the two soils
      rose with increasing levels of algal amendment but were also influenced by
      existing soil P levels. Results from plant growth experiments showed that 20-day
      old cucumber and corn seedlings grown in algae-amended potting mix contained 15
      20% of applied N, 46-60% of available N, and 38-60% of the applied P. Seedlings
      grown in algae-amended potting mixes were equivalent to those grown with
      comparable levels of fertilizer amended potting mixes with respect to seedling
      dry weight and nutrient content. These results suggest that dried algal biomass
      produced from treatment of anaerobically digested dairy manure can substitute for
      commercial fertilizers used for potting systems.

PMID- 15491827
TI  - Effect of natural zeolite on methane production for anaerobic digestion of
      ammonium rich organic sludge.
AB  - The effect of an inorganic additive on the methane production from NH(4+)-rich
      organic sludge during anaerobic digestion was investigated using different kinds
      of inorganic adsorbent zeolites (mordenite, clinoptilolite, zeolite 3A, zeolite
      4A), clay mineral (vermiculite), and manganese oxides (hollandite, birnessite).
      The additions of inorganic materials resulted in significant NH4+ removals from
      the natural organic sludge ([NH4+]=1, 150 mg N/l), except for the H-type zeolite
      3A and birnessite. However, an enhanced methane production was only achieved
      using natural mordenite. Natural mordenite also enhanced the methane production
      from the sludge with a markedly high NH4+ concentration (4500 mg N/l) during
      anaerobic digestion. Chemical analyses of the sludge after the digestion showed
      considerable increases in the Ca2+ and Mg2+ concentrations in the presence of
      natural mordenite, but not with synthetic zeolite 3A. The effect of Ca2+ or Mg2+
      addition on the methane production was studied using Na(+)-exchanges mordenite
      and Ca2+ or Mg(2+)-enriched sludge. The simultaneous addition of Ca2+ ions and
      Na(+)-exchanged mordenite enhanced the methane production; the amount of produced
      methane was about three times greater than that using only the Na(+)-exchanged
      mordenite. In addition, comparing the methane production by the addition of
      natural mordenite or Ca2+ ions, the methane production with natural mordenite was
      about 1.7 times higher than that with only Ca2+ ions. The addition of 5% and 10%
      natural mordenite were suitable condition for obtaining a high methane
      production. These results indicated that the Ca2+ ions, which are released from
      natural mordenite by a Ca2+/NH4+ exchange, enhanced the methane production of the
      organic waste at a high NH4+ concentration. Natural mordenite has a synergistic
      effect on the Ca2+ supply as well on the NH4+ removal during anaerobic digestion,
      which is effective for the mitigation of NH4+ inhibition against methane
      production.

PMID- 15491828
TI  - Preparation and evaluation of lignosulfonates as a dispersant for gypsum paste
      from acid hydrolysis lignin.
AB  - In order to effectively utilize a by-product of the acid saccharification process
      of woody materials, the chemical conversion of guaiacyl sulfuric acid lignin
      (SAL), one of the acid hydrolysis lignins, into water-soluble sulfonated products
      with high dispersibitity was investigated. At first, SAL was phenolated (P-SAL)
      to enhance the solubility and reactivity. Lignosulfonates were prepared from P
      SAL by three methods of hydroxymethylation followed by neutral sulfonation (two
      step method), sulfomethylation (one-step method) and arylsulfonation.
      Surprisingly, all prepared lignosulfonates possessed 30 to 70% higher
      dispersibility for gypsum paste than the commercial lignosulfonate. Evaluation of
      the preparations for gypsum paste suggested that the higher molecular weights and
      sulfur contents of the preparations increased their dispersibility.

PMID- 15491829
TI  - Characterization of natural organic matter (NOM) derived from sewage sludge
      compost. Part 1: chemical and spectroscopic properties.
AB  - In this study changes in the properties of natural organic matter (NOM) were
      studied during composting of sewage sludge in a laboratory experiment using the
      pile method. Typical physicochemical parameters were measured during 53 days of
      composting including humic fractions. The effects of humification on the
      molecular properties of humic acids (HA) were investigated by 13C CP/MAS NMR
      spectroscopy. On the basis of chemical analyses, 53 days of composting sewage
      sludge with structural material can be divided into three phases: (i) domination
      of rapid decomposition of non-humic, easily biodegradable organic matter (two to
      three weeks), (ii) domination of organic matter humification and formation of
      polycondensed, humic-like substances (the next two weeks), (iii) stabilization of
      transformed organic material and weak microbial activity. Spectroscopic
      characterization (13C NMR) of compost humic acids reveals changes in their
      structures during maturation. The changes are highly correlated with the
      processes taking place in bulk compost.

PMID- 15491830
TI  - Characterization of natural organic matter (NOM) derived from sewage sludge
      compost. Part 2: multivariate techniques in the study of compost maturation.
AB  - This study presents the results of chemometric data analysis which describes the
      maturation of sewage sludge compost. The compost was characterized at different
      stages of maturation by various chemical and spectroscopic parameters including
      carbon and nitrogen content, humic substances content, UV-Vis and 13C NMR. The
      data set of compost characteristics was analyzed using multivariate methods:
      cluster analysis (CA) and principal component analysis (PCA). The results enabled
      the determination of three groups of compost samples at different stages of
      maturation that correspond to three stages of composting: (i) domination of rapid
      decomposition of non-humic, easily biodegradable organic matter, (ii) domination
      of organic matter humification and formation of polycondensed, humic-like
      substances (the next 2 weeks), (iii) stabilization of transformed organic
      material and weak microbial activity. The multivariate techniques also enabled
      the identification of main parameters that change during different stages of
      composting the most.

PMID- 15491831
TI  - Selection of medium components by Plackett-Burman design for production of L(+)
      lactic acid by Lactobacillus amylophilus GV6 in SSF using wheat bran.
AB  - Plackett-Burman design was employed for screening 15 parameters for production of
      L(+) lactic acid from wheat bran, an inexpensive substrate and solid support, by
      Lactobacillus amylophilus GV6 in solid state fermentation (SSF). Eleven nutrients
      belonging to two categories viz.; nitrogen sources and salt sources along with
      three physical parameters and a buffer were screened. This design screens n
      variables in n + 1 number of experiments. Coefficients and sum of squares ratio
      in percentage (SS%) of these variables were calculated by subjecting the
      experimental data to statistical analysis. The nitrogen sources peptone, yeast
      extract and tri-ammonium citrate, along with NaH2PO4.2H2O and Tween 80, were
      found to influence productivity, which can be further optimized for increased
      lactic acid production. Use of this design is scarce in solid state fermentation
      and has not been attempted previously for single step conversion of starch to
      L(+) lactic acid using a bacterial system.

PMID- 15491832
TI  - Production of cellulase by Trichoderma reesei from dairy manure.
AB  - Cellulase production by the fungi Trichoderma reesei was studied using dairy
      manure as a substrate. Data showed that T. reesei RUT-C30 had higher cellulase
      production than T. reesei QM 9414 and that a homogenized manure, treated by a
      blender to reduce fiber size, led to higher cellulase production. The cellulase
      production was further optimized by growing T. reesei RUT-C30 on homogenized
      manure. The effects of manure concentration, pH, and temperature on cellulase
      production were investigated with optimal parameter values determined to be 10
      g/l manure (dry basis), 25.5 degrees C, and pH 5.7, respectively. Elimination of
      CaCl2, MgSO4, nitrogen sources (NH4+ and urea) and trace elements (Fe2+, Zn2+,
      Co2+ and Mn2+) from the original salt solution had no negative influence on the
      cellulase production, while phosphate elimination did reduce cellulase
      production. Based on above results, the final medium composition was simplified
      with manure additives being KH2PO4, tween-80 and CoCl2 only. Using this medium
      composition and a reaction time of 6-8 days, a maximum cellulase production
      activity of 1.74 IU/ml of filter paper activity, 12.22 IU/ml of CMCase activity,
      and 0.0978 IU/ml of beta-glucosidase was obtained. This filter paper activity is
      the highest ever reported in cellulase production from agricultural wastes.

PMID- 15491833
TI  - Hydrolysis rates, methane production and nitrogen solubilisation of grey waste
      components during anaerobic degradation.
AB  - Municipal grey waste (i.e. the remaining fraction in municipal waste management
      systems in which putrescibles (biowaste) and other recyclables (paper, metals,
      glass) are source-segregated) was manually sorted into six main fractions on the
      basis of composition and also separated by sieving (100 mm mesh size) into two
      fractions, oversized and undersized, respectively. In practice, in waste
      management plant the oversized fraction is (or will be) used to produce refuse
      derived fuel and the undersized landfilled after biological stabilisation. The
      methane yields and nitrogen solubilisation of the grey waste and the different
      fractions (all studied samples were first milled to 5 mm particle samples) were
      determined in a 237-day methane production batch assay and in a water elution
      test, respectively. The grey waste was found to contained remnants of
      putrescibles and also a high amount of other biodegradable waste, including
      packaging, cartons and cardboard, newsprint, textiles and diapers. These waste
      fractions comprised 41%-w/w of the grey waste and produced 40-210 m3 methane
      (total solids (TS))(-1) and less than 0.01 g NH4-N kg TS(added)(-1) except
      diapers which produced 9.8 g NH4-N kg TS(added)(-1) in the batch assays. In the
      case of the two sieved fractions and on mass bases, most of the methane
      originated from the oversized fraction, whereas most of the NH4-N was solublised
      from the undersized fraction. The first-order kinetic model described rather well
      the degradation of each grey waste fraction and component, showing the different
      components to be in the range 0.021-0.058 d(-1), which was around one-sixth of
      the values reported for the source-segregated putrescible fraction of MSW.

PMID- 15491834
TI  - Distribution of carbon, nitrogen and phosphorus in water-stable aggregates of an
      organic waste amended Ultisol in southern Nigeria.
AB  - This study was undertaken to evaluate the effects of different organic and
      inorganic amendments on nutrient (C, N and P) distribution in water-stable
      aggregates (WSA) of a degraded tropical Ultisol at Nsukka in southern Nigeria.
      The treatments were control (C), inorganic fertilizer (F) (N-P-K, 12-12-17), rice
      mill wastes (RW), RW + F, poultry manure (PM) and RW + PM. These were arranged in
      a randomized complete block design (RCBD) with four replications. At 0, 3, 6 and
      12 months after application of the amendments, topsoil (0-20 cm) samples were
      collected from all the treatments, dried and separated into 4.75-2.0, 2.0-1.0,
      1.0-0.5, 0.50-0.25 and <0.25 mm aggregates classes by wet sieving. The
      mesoaggregates fraction (1.0-0.50 mm) made up the highest percentage of the whole
      soil irrespective of the treatments. From the sixth month, the treatments
      generally reduced the proportion of these mesoaggregates as well as those of the
      microaggregates (<0.25 mm diameter) while increasing those of the other sizes.
      The largest (>2.0 mm) and the smallest (<0.25 mm) aggregates were preferentially
      enriched in C and N relative to the 2.0-0.25 mm aggregates in all the treatments,
      whereas P distribution within the aggregates was random. There was a low, but
      significant correlation between organic carbon and mean-weight diameter (MWD) of
      the aggregates. The correlation between C and N within the aggregates was also
      positive (r = 0.917) and highly significant (P < 0.01). The implication of these
      results for management of these soils is discussed.

PMID- 15491835
TI  - Feasibility of treating partially soluble wastewater in anaerobic sequencing
      batch biofilm reactor (ASBBR) with mechanical stirring.
AB  - This work reports on the treatment of partially soluble wastewater in an
      anaerobic sequencing batch biofilm reactor, containing biomass immobilized on
      polyurethane matrices and stirred mechanically. The results showed that agitation
      provided optimal mixing and improved the overall organic matter consumption
      rates. The system showed to be feasible to enhance the treatment of partially
      soluble wastewaters.

PMID- 15491836
TI  - Enhanced motor unit rate coding with improvements in a force-matching task.
AB  - These data describe improved modulation of discharge rates (rate coding) of first
      dorsal interosseous motor units throughout the acquisition of a complex force
      matching skill involving isometric index finger abduction. In each of 15
      consecutive trials, subjects attempted to match their force to a trajectory
      consisting of the sum of two sine waves (0.15 and 0.5 Hz) and random oscillations
      (overall mean force level approximately 20% MVC). Reductions in root-mean-square
      (RMS) error of each subject's force relative to the trajectory indicated
      substantial improvements in force-matching ability (F = 33.8, p < 0.001). With
      the acquisition of this new skill, there was increased amplitude modulation of
      muscular force near both dominant frequencies of the force-matching trajectory (F
      = 10.6, p = 0.008). The standard deviation and coefficient of variation of motor
      unit inter-spike intervals both decreased with improved performance indicating a
      general reduction in the amplitude of firing rate modulations (SD: F = 18.69, p =
      0.001; CV: F = 43.6, p < 0.001). After skill acquisition, there was decreased
      firing rate modulation outside of the two dominant frequencies and increased
      amplitude of firing rate modulation at the higher of the two dominant frequencies
      (0.5 Hz, F = 8.23, p = 0.015). These findings indicate that improved precision of
      rate coding was a contributor to the acquisition of the new force-matching task.
      That the change in rate coding was frequency dependent suggests that factors
      other than frequency coding may contribute to the improved force matching at 0.15
      Hz.

PMID- 15491837
TI  - Arthrogenic muscle response induced by an experimental knee joint effusion is
      mediated by pre- and post-synaptic spinal mechanisms.
AB  - Knee joint effusion results in quadriceps inhibition and is accompanied by
      increased excitability in the soleus musculature. The purpose of this study was
      to determine if soleus arthrogenic muscle response is regulated by pre- or post
      synaptic spinal mechanisms. Ten healthy adults (two females and eight males) were
      measured on two occasions. At the first session, subjects had their knee injected
      with 60 ml of saline and in the other session they did not. Pre- and post
      synaptic spinal mechanisms were measured at baseline, immediately following a
      needle stick, immediately following a Xylocaine injection, and 25 and 45 min post
      saline injection. A mixed effects model for repeated measures was used to analyze
      each dependent variable. The a priori alpha level was set a P < or = 0.05. The
      percentage of the unconditioned reflex amplitude for recurrent inhibition (P <
      0.0001) and reflex activation history (P < 0.0001) significantly increased from
      baseline at 25 and 45 min post-effusion. Soleus arthrogenic muscle response seen
      following knee joint effusion is mediated by both pre- and post-synaptic
      mechanisms. In conclusion, the arthrogenic muscle response seen in the soleus
      musculature following joint effusion is regulated by both pre- and post-synaptic
      control mechanisms. Our data are the first step in understanding the neural
      networks involved in the patterned muscle response that occurs following joint
      effusion.

PMID- 15491838
TI  - Effect of hip and ankle muscle fatigue on unipedal postural control.
AB  - Fatigue and deficits in postural control may predispose musculoskeletal injury.
      The purpose of this study was to examine the effects of fatigue at the hip and
      ankle during frontal plane movements on postural control during single-leg
      stance. Thirteen healthy volunteers completed two testing sessions 1 week apart
      consisting of isokinetic fatigue of the frontal plane movers of either the ankle
      or hip with measures of static unipedal postural control taken before and after
      fatigue. Postural control was assessed during three 30-s trials of unilateral
      stance with eyes open before and after the fatigue protocol at each testing
      session. Mean center of pressure (COP) excursion velocity in the sagittal and
      frontal planes was compared between pre- and post-fatigue across the two joints.
      Fatigue of the hip musculature led to postural control impairments in the frontal
      and sagittal planes, while fatigue of the ankle musculature did not significantly
      impair postural control in either plane. Our results suggest that there is a
      greater effect of localized fatigue of the frontal plane movers of the hip
      compared to the ankle on maintenance of a postural control in single-leg stance.

PMID- 15491839
TI  - Electromechanical delay estimated by using electromyography during cycling at
      different pedaling frequencies.
AB  - The purpose of this study was to propose a new method that can be used to
      calculate electromechanical delay (EMD) without the measurement of forces. A
      secondary purpose, as an example of the importance of measuring EMD, was to
      predict muscle force development events based on the EMG activity of selected
      muscles during cycling at different pedaling frequencies. EMD was estimated using
      newly derived equations based on activation dynamics hypothesis. Tibialis
      anterior (TA) and soleus (SL) muscles of 16 male participants were studied while
      subjects pedaled at targeted cadences of 60, 80, and 100 revolutions per minute.
      The estimated EMDs of TA and SL were significantly different from each other with
      means of 68.1 and 88.7 ms, respectively. The average crank angle for the
      initiation and time to peak TA contraction was estimated at 75 +/- 35 degrees and
      26 +/- 15 degrees before the crank reached top-dead-center (TDC), while the
      contraction ended at 31 +/- 19 degrees after the TDC on average. The projected
      starting, peak and end angles of SL contraction activity were 45 +/- 18 degrees ,
      123 +/- 13 degrees, and 218 +/- 35 degrees after the TDC, respectively. There was
      no difference among different pedaling cadences observed for these mechanical
      events. The proposed method was proven to be effective in studying EMD and
      estimate muscle contraction patterns during cycling.

PMID- 15491840
TI  - Responsiveness of the H reflex to loading and posture in patients following
      stroke.
AB  - The objective of the research was to examine the effects of loading and posture
      on motoneuronal excitability of the triceps surae (TS) for patients with
      hemiplegia. Twelve healthy subjects and 12 patient subjects with post-stroke
      hemiparesis (onset period: 3-60 months) were enrolled in this study. The subjects
      were instructed to remain in quiet sitting with the test knee straight and three
      standing conditions of different superincumbent loads by shifting body weight to
      the test leg (10%, 50%, and 90% of body weight), while the H reflexes and M waves
      of the TS were measured. The results clearly indicated that H reflex amplitudes
      were not affected by different loading conditions in standing for both healthy
      subjects and patients who had a previous stroke. In addition, the H reflex
      amplitude in quiet standing for healthy subjects was significantly downward
      modulated relative to that in relaxed sitting with the test knee straight, but
      this posturally driven modulation was impaired in patients following stroke.
      Current electrophysiological findings imply that body weight as a means for
      rehabilitation facilitation had little immediate effect on paretic TS, and
      absence in postural gating of reflex excitability appeared to be an incentive for
      postural instability resulting from post-stroke hemiparesis.

PMID- 15491841
TI  - Electromyographical assessment on muscular fatigue--an elaboration upon
      repetitive typing activity.
AB  - The objectives of this study were to quantify the electromyographic activities
      (EMG) of finger muscles during prolonged, low-forces, and repetitive typing with
      an ergonomically designed VDT workstation, as well as to analyze the occurrence
      and the possible mechanisms of muscular fatigue in touched typists. Thirty
      healthy female typists were recruited to type consecutively for 2 h. The surface
      EMG of extensor digitorum communis (EDC) and flexor digitorum superficialis (FDS)
      of both hands was recorded throughout the entire test. Electrical activity (EA)
      and median frequency (MDF) were calculated, and then regressed against the time
      courses to obtain the slopes of progress. Further analysis of the EMG parameters
      was done by the joint analysis of spectra and amplitudes (JASA). The results
      indicated that maximum voluntary electrical activation (MVE) decreased after 2-h
      typing, and did not recover to the initial values even after a 10-min break.
      Besides, there was a trend of decrement in frequency throughout the entire trail,
      and the MDF reduced by 25% in comparison with the initial values. With the JASA
      plot, 74% of the muscles manifested fatigue after 2-h typing activity.
      Furthermore, we observed that the EDC muscles were more susceptible to muscular
      fatigue than the FDS muscles. In conclusion, prolonged consecutive typing may
      induce muscular fatigue in the healthy typists even in an ergonomic typing
      environment.

PMID- 15491842
TI  - Quantitative assessment of upper limb muscle fatigue depending on the conditions
      of repetitive task load.
AB  - The aim of this study was to discriminate fatigue of upper limb muscles depending
      on the external load, through the development and analysis of a muscle fatigue
      index. Muscle fatigue is expressed by a fatigue index based on an amplitude
      parameter (calculated in the time domain) and a fatigue index based on a
      frequency parameter (a parameter calculated in the frequency domain). The fatigue
      index involves a regression function that describes changes in the EMG signal
      parameter, time elapsing before muscle fatigue and the probability of specific
      trends in changes in EMG parameters for the population under study. The
      experimental study covered a group of 10 young men. During the study, they
      exerted force at a specific level and for a specific time in 12 load variants.
      During the study, EMG signals from four muscles of the upper limb were recorded
      (trapezius pars descendents, biceps brachii caput breve, extensor carpi radialis
      brevis, flexor carpi ulnaris). For each variant and for each examined muscles,
      the value of the fatigue index was calculated. Values of that index
      quantitatively expressed fatigue of a specific muscle in a specific load variant.
      A statistical analysis indicated variation in the fatigue of the biceps brachii
      caput breve, extensor carpi radialis brevis, and flexor carpi ulnaris muscles
      depending on the external load (load variant) according to the task performed
      with the upper limb. The study demonstrated usefulness of the fatigue index in
      expressing quantitatively muscle fatigue and in discriminating muscle fatigue
      depending on the external load.

PMID- 15491843
TI  - The relationships between active extensibility, and passive and active stiffness
      of the knee flexors.
AB  - Insufficient active knee flexor stiffness may predispose the anterior cruciate
      ligament to injury. Insufficient passive stiffness may result in insufficient
      active stiffness. Similarly, higher levels of musculotendinous extensibility may
      inhibit active and passive muscle stiffness, potentially contributing to an
      increased risk of injury. The literature is both limited and inconsistent
      concerning relationships between extensibility, passive stiffness, and active
      stiffness. Extensibility was measured as the maximal active knee extension angle
      from a supine position with the hip flexed to 90 degrees . Passive stiffness was
      calculated as the slope of the moment-angle curve resulting from passive knee
      extension. Active stiffness was assessed via acceleration associated with damped
      oscillatory motion about the knee. Stepwise multiple regression indicated that
      passive stiffness accounted for 25% of active muscle stiffness variance. The
      linear combination of extensibility and passive stiffness explained only 2% more
      variance compared to passive stiffness alone. Musculotendinous extensibility was
      moderately related to passive muscle stiffness, and weakly related to active
      muscle stiffness. The moderate relationship observed between active and passive
      stiffness emphasizes the dependence of active muscle stiffness on cross-bridge
      formation, and the relatively smaller contribution from parallel elastic tissues.
      Additionally, heightened extensibility does not appear to be a predisposing
      factor for reduced muscle stiffness.

PMID- 15491844
TI  - The effect of foot orthotics on myoelectric fatigue in the vastus lateralis
      during a simulated skier's squat.
AB  - Fatigue in the legs is a problem experienced by skiers. It has been suggested
      that optimal orthotics may reduce muscle fatigue for a given movement task by
      minimising muscle activity (Med. Sci. Sports Exerc. 31 (1999) S421). The aims
      were to determine whether EMG would provide an independent method of analysing
      myoelectric fatigue in the vastus lateralis (VL) during a skier's squat and
      whether orthotics could affect this fatigue response. Six skiers performed
      skier's squats for as long as possible with no orthotic, low volume orthotics and
      high volume orthotics in their ski boots. Bipolar, active surface electrodes
      recorded EMG activity in the VL throughout each squat. Results for the EMG median
      frequency showed a significant shift in the power density spectrum towards the
      lower frequencies (P < 0.05) at the end of the contraction, suggesting that
      myoelectric fatigue was occurring and was measurable using EMG. All conditions
      displayed a significant decrease in median frequency at the end of the
      contraction (P = 0.001). The high volume orthotic showed a significant reduction
      in myoelectric fatigue, however, there was no difference in the duration of
      squats across the three conditions (P > 0.05). Subjective and objective findings
      support the use of the high volume foot orthotic for skiers.

PMID- 15491845
TI  - Activation of shoulder muscles in healthy men and women under isometric
      conditions.
AB  - PURPOSE: Due to the low osseous lead of the shoulder joint a large portion of the
      shoulder muscles, in addition to executing movements, deals with stabilising
      tasks. This requires a permanent readjustment of the intermuscular co-ordination
      of all involved muscles. The aim of the study was to verify the existence of
      gender dependent differences in intramuscular co-ordination patterns of shoulder
      muscles. METHOD: Fifteen healthy men and nine healthy women, who executed 24
      isometric exercises in sagittal, frontal and horizontal planes with a loading of
      50% of their individual isometric maximum force, were investigated. In every
      plane, four angular positions were chosen and both opposite force directions were
      measured, respectively. SEMG was taken from 13 muscles of the shoulder and the
      upper arm. Due to inter-individual differences SEMG amplitudes were normalised.
      RESULTS: Gender specific differences of functional intermuscular co-ordination
      patterns could be proven systematically. Women showed less activation of muscles
      acting in the main force direction. In addition, those muscles less necessary for
      the actual force production were more activated in women than in men.
      CONCLUSIONS: Functionally comparable shoulder function showed a gender dependency
      in terms of functional intermuscular co-ordination.

PMID- 15491846
TI  - Comparison of surface electromyography and myotonometric measurements during
      voluntary isometric contractions.
AB  - OBJECTIVES: Muscle stiffness increases during muscle contraction. The purpose of
      this study was to determine the strength of the correlation between myotonometric
      measurements of muscle stiffness and surface electromyography (sEMG) measurements
      during various levels of voluntary isometric contractions of the biceps brachii
      muscle. SUBJECTS: Eight subjects (four female; four male), with mean age of 30.6
      +/- 8.23, volunteered to participate in this study. METHODS: Myotonometer and
      sEMG measurements were taken simultaneously from the right biceps brachii muscle.
      Data were obtained: (1) at rest, (2) while the subject held a 15 lb (6.8 kg)
      weight isometrically and, (3) during a maximal voluntary isometric contraction.
      Myotonometer force-displacement curves (amount of tissue displacement to a given
      unit of force applied perpendicular to the muscle) were compared with sEMG
      measurements using Pearson's product-moment correlation coefficients. RESULTS:
      Myotonometer and sEMG measurement correlations ranged from -0.70 to -0.90. The
      strongest correlations to sEMG were from Myotonometer force measurements between
      1.00 and 2.00 kg. CONCLUSIONS: Myotonometer and sEMG measurements were highly
      correlated. Tissue stiffness, as measured by the Myotonometer, appears capable of
      assessing changes in muscle activation levels.

PMID- 15491847
TI  - Effects of long-term inhibition of neuronal nitric oxide synthase (NOS1) in
      uninephrectomized diabetic rats.
AB  - Nitric oxide (NO) has been implicated in the pathogenesis of renal hemodynamic
      changes in diabetes mellitus (DM). However, the role of NO in the pathophysiology
      of diabetic nephropathy remains controversial. Renal hemodynamic changes in
      experimental DM can be acutely normalized by selective inhibition of neuronal NO
      synthase (nNOS). This observation suggests a nephroprotective potential of nNOS
      inhibition in DM. To explore this issue we assessed the long-term effects (12
      weeks) of selective nNOS inhibition with the specific inhibitor S-methyl-L
      thiocitrulline (SMTC) in uninephrectomized control and streptozotocin-diabetic
      rats. No beneficial effects of SMTC were observed in nondiabetic controls. In
      contrast, SMTC delayed the development of proteinuria (32+/-8 vs. 53+/-9 mg/24h,
      week 8, p < 0.05) and glomerulosclerosis (GS, 0.30+/-0.08 vs. 0.57+/-0.05, p <
      0.05) in diabetic rats. These effects coincided with early effects of treatment
      on the glomerular filtration rate, and were associated with lower renal
      expression of nNOS. Furthermore, SMTC-treated diabetic rats demonstrated reduced
      weight gain and urinary sodium excretion as compared to vehicle-treated
      counterparts, despite similar metabolic control and blood pressure. In summary,
      long-term nNOS inhibition had modest nephroprotective effects in
      uninephrectomized diabetic rats. These effects may be mediated by renal
      hemodynamic mechanisms, as well as by lower food (protein) intake.

PMID- 15491848
TI  - Effects of aminoguanidine and antioxidant erdosteine on bleomycin-induced lung
      fibrosis in rats.
AB  - Reactive oxygen and nitrogen species have been implicated in the pathogenesis of
      bleomycin-induced lung fibrosis. The effects of aminoguanidine and erdosteine on
      the bleomycin-induced lung fibrosis were evaluated in rats. The animals were
      placed into five groups: Vehicle + vehicle, vehicle + bleomycin (2.5 U/kg),
      bleomycin + aminoguanidine (200 mg/kg), bleomycin + erdosteine (10 mg/kg), and
      bleomycin + erdosteine + aminoguanidine. Bleomycin administration resulted in
      prominent lung fibrosis as measured by lung hydroxyproline content and lung
      histology, which is completely prevented by erdosteine and aminoguanidine. A
      strong staining for nitro tyrosine antibody in lung tissue and increased levels
      of lung NO were found in bleomycin group, that were significantly reduced by
      aminoguanidine and erdosteine. Aminoguanidine and erdosteine significantly
      prevented depletion of superoxide dismutase and glutathione peroxidase and
      elevated myeloperoxidase activities, malondialdehyde level in lung tissue
      produced by bleomycin. Data presented here indicate that aminoguanidine and
      erdosteine prevented bleomycin-induced lung fibrosis and that nitric oxide
      mediated tyrosine nitration of proteins plays a significant role in the
      pathogenesis of bleomycin-induced lung fibrosis. Also our data suggest that
      antifibrotic affect of antioxidants may be due to their inhibitory effect on
      nitric oxide generation in this model.

PMID- 15491849
TI  - Peripheral blood monocytes show morphological pattern of activation and decreased
      nitric oxide production during acute Chagas' disease in rats.
AB  - Peripheral blood monocytes (PBM) recruitment is a rapid and remarkable phenomenon
      during acute infection with the intracellular protozoan parasite Trypanosoma
      cruzi, the causative agent of Chagas' disease. The functional capabilities of
      these cells during the infection, however, are poorly understood. The purpose of
      the present study was to determine whether PBM are morphologically activated and
      produce nitric oxide (NO), a mediator of host cell defense when challenged with
      the parasite at different time points of acute disease. In parallel, the parasite
      load was monitored in the blood and heart, a target organ of the disease, as well
      as the PBM numbers. The infection did not induce NO release by PBM, although
      these cells exhibited a clear morphological pattern of activation characterized
      by irregular surface, increase of organelle amount, especially Golgi complex, and
      cell size. On the contrary, there was significant inhibition of NO production by
      PBM at the beginning (day 6) and end of acute disease (day 20). At this time, the
      levels of NO were inversely related to the arginase activity, an enzyme that
      affects the NO synthesis. The mobilization process of PBM occurred in parallel to
      parasite load and was associated with the resolution mechanism of parasitemia and
      heart parasitism. Our results showed that activated PBM are notably involved in
      the host response to the acute T. cruzi infection in rats. However, the in vivo
      NO production by these cells seems to be inhibited during the acute Chagas'
      disease through a mechanism involving the arginase pathway.

PMID- 15491850
TI  - Mechanism of NO-mediated oxidative and nitrative DNA damage in hamsters infected
      with Opisthorchis viverrini: a model of inflammation-mediated carcinogenesis.
AB  - Inflammation mediated by infection is an important factor causing carcinogenesis.
      Opisthorchis viverrini (OV) infection is a risk factor of cholangiocarcinoma
      (CHCA), probably through chronic inflammation. Formation of 8-nitroguanine and 8
      oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), and expression of inducible nitric
      oxide synthase (iNOS) and heme oxygenase-1 (HO-1) were assessed in the liver of
      hamsters infected with OV. We newly produced specific anti-8-nitroguanine
      antibody without cross-reaction. Double immunofluorescence staining revealed that
      8-oxodG and 8-nitroguanine were formed mainly in the same inflammatory cells and
      epithelium of bile ducts from day 7 and showed the strongest immunoreactivity on
      days 21 and 30, respectively. It is noteworthy that 8-oxodG and 8-nitroguanine
      still remained in epithelium of bile ducts on day 180, although amount of alanine
      aminotransferase activity returned to normal level. A time course of 8
      nitroguanine was associated with iNOS expression. Furthermore, this study
      demonstrated that HO-1 expression and subsequent iron accumulation may be
      involved in enhancement of oxidative DNA damage in epithelium of small bile
      ducts. In conclusion, nitrative and oxidative DNA damage via iNOS expression in
      hamsters infected with OV may participate in CHCA carcinogenesis.

PMID- 15491851
TI  - Prostaglandin E2 and dexamethasone regulate eosinophil differentiation and
      survival through a nitric oxide- and CD95-dependent pathway.
AB  - Apoptosis, involving both CD95/CD95L interactions and their modulation by nitric
      oxide (NO), is central to regulation of mature eosinophil numbers. However, its
      role in regulating eosinophil production from bone-marrow precursors is unknown.
      We examined the effects of prostaglandin E2 (PGE2) and dexamethasone on
      eosinophil differentiation and survival in murine bone-marrow cultures, and their
      relationship to: NO production as well as CD95/CD95L-dependent apoptosis. Bone
      marrow cultures were established with IL-5, alone or in association with PGE2,
      dexamethasone or both. PGE2 (10(-7)M) inhibited eosinophil differentiation by
      selectively inducing apoptosis in developing eosinophils. Dexamethasone (10(-7)M)
      protected developing eosinophils from PGE2-induced apoptosis. Since dexamethasone
      prevents induction of nitric oxide synthase (NOS), we evaluated the role of NO in
      the effects of both PGE2 and dexamethasone. NO donors (SNAP and SNP) down
      modulated eosinophil precursor responses to IL-5. SNAP induced apoptosis through
      a dexamethasone-resistant mechanism. The NOS inhibitors, Nomega-nitro-L-arginine
      and aminoguanidine, blocked the effects of PGE2 on developing eosinophils. PGE2
      was ineffective in bone-marrow from knockout mice lacking inducible NOS. PGE2 up
      regulated CD95 and CD95L expression in developing eosinophils. Neither PGE2 nor
      SNAP were effective in cultures from CD95L-deficient gld mice. These data suggest
      that PGE2 induces apoptosis in developing eosinophils through inducible NOS,
      leading to NO-dependent activation of the CD95L/CD95 pathway, while dexamethasone
      antagonizes the effects of PGE2 on the same targets.

PMID- 15491852
TI  - Differential regulation of glomerular and interstitial endothelial nitric oxide
      synthase expression in the kidney of hibernating ground squirrel.
AB  - Hibernating animals transiently reduce renal function during their hypothermic
      periods (torpor), while completely restoring it during their periodical rewarming
      to euthermia (arousal). Moreover, structural integrity of the kidney is preserved
      throughout the hibernation. Nitric oxide (NO) generated by endothelial nitric
      oxide synthase (eNOS) is a crucial vasodilatory mediator and a protective factor
      in the kidney. We investigated renal NOS expression in hibernating European
      ground squirrels after 1 day and 7 days of torpor (torpor short, TS, and torpor
      long, TL, respectively), at 1.5 and at 10 h of rewarming (arousal short, AS, and
      arousal long, AL, respectively), and in continuously euthermic animals after
      hibernation (EU). For that purpose, we performed NOS activity assay,
      immunohistochemistry and real-time PCR analysis. Immunohistochemistry revealed a
      decreased glomerular eNOS expression in hibernating animals (TS, TL, AS, and AL)
      compared to non-hibernating animals (EU, p < 0.05), whereas no difference was
      found in the expression of interstitial eNOS. Expression of iNOS and nNOS did not
      differ between all groups. The reduced glomerular eNOS was associated with a
      significantly lower eNOS mRNA levels and NOS activity of whole kidney during
      torpor and arousal (TS, TL, AS, and AL) compared to EU. In all methods used,
      torpid and aroused squirrels did not differ. These results demonstrate
      differential regulation of eNOS in glomeruli and interstitium of hibernating
      animals, which is unaffected during arousal. The differential regulation of eNOS
      may serve to reduce ultrafiltration without jeopardizing tubular structures
      during hibernation.

PMID- 15491853
TI  - Nitric oxide-scavenging activity of polyhydroxylated fullerenol, C60(OH)24.
AB  - Investigation of the possible nitric oxide-scavenging activity of hydroxylated
      derivative of fullerene, fullerenol C60(OH)24, demonstrated that it expressed
      direct scavenging activity toward nitric oxide radical (NO) liberated within
      solution of sodium nitroprusside (SNP), a well known NO donor. In parallel, pre
      treatment (30') with intratesticular injection of fullerenol (60 microg/each
      testis) prevented NO-induced decrease of catalase, glutathione transferase and
      glutathione peroxidase activities in the denucleated fraction of interstitial
      testicular cells of adult rats 2 h after intratesticular injection of SNP (20
      microg/each testis). In addition, fullerenol decreased formation of
      thiobarbituric acid-reactive substances (TBA-RS) with similar efficiency as
      butylated hydroxy toluen (BHT), a well known antioxidant. Also, fullerenol
      expressed certain scavenging activity toward superoxide anion (O2-) in
      xanthine/xanthine oxidase system. In summary, results obtained in this study
      confirmed free radical-scavenging activity of fullerenol, and according to our
      knowledge, it is the first evidence of direct NO-quenching activity of
      hydroxylated C60 derivative in different milieu.

PMID- 15491854
TI  - Microbial export of lactic and 3-hydroxypropanoic acid: implications for
      industrial fermentation processes.
AB  - Lactic acid and 3-hydroxypropanoic acid are industrially relevant microbial
      products. This paper reviews the current knowledge on export of these compounds
      from microbial cells and presents a theoretical analysis of the bioenergetics of
      different export mechanisms. It is concluded that export can be a key constraint
      in industrial production, especially under the conditions of high product
      concentration and low extracellular pH that are optimal for recovery of the
      undissociated acids. Under these conditions, the metabolic energy requirement for
      product export may equal or exceed the metabolic energy yield from product
      formation. Consequently, prolonged product formation at low pH and at high
      product concentrations requires the involvement of alternative, ATP-yielding
      pathways to sustain growth and maintenance processes, thereby reducing the
      product yield on substrate. Research on export mechanisms and energetics should
      therefore be an integral part of the development of microbial production
      processes for these and other weak acids.

PMID- 15491855
TI  - Metabolic network simulation using logical loop algorithm and Jacobian matrix.
AB  - A novel method to accomplish efficient numerical simulation of metabolic networks
      for flux analysis was developed. The only inputs required are the set of
      stoichiometric balances and the atom mapping matrices of all components of the
      reaction network. The latter are used to automatically calculate isotopomer
      mapping matrices. Using the symbolic toolbox of MATLAB the analytical solution of
      the stoichiometric balance equation system, isotopomer balances and the
      analytical Jacobian matrix of the total set of stoichiometric and isotopomer
      balances are created automatically. The number of variables in the isotopomer
      distribution equation system is significantly reduced applying modified
      isotopomer mapping matrices. These allow lumping of several consecutive
      isotopomer reactions into a single one. The solution of the complete system of
      equations is improved by implementing an iterative logical loop algorithm and
      using the analytical Jacobian matrix. This new method provided quick and robust
      convergence to the root of such equation systems in all cases tested. The method
      was applied to a network of lysine producing Corynebacterium glutamicum. The
      resulting equation system with the dimension of 546 x 546 was directly derived
      from 12 isotopomer balance equations. The results obtained yielded identical
      labeling patterns for metabolites as compared to the relaxation method.

PMID- 15491856
TI  - Metabolic engineering of the indole pathway in Catharanthus roseus hairy roots
      and increased accumulation of tryptamine and serpentine.
AB  - Transgenic hairy roots of Catharanthus roseus were established with
      glucocorticoid inducible tryptophan decarboxylase (TDC) expression alone or in
      combination with inducible expression of a feedback-resistant anthranilate
      synthase alpha subunit (ASalpha) from Arabidopsis. Northern blot analysis
      confirmed transcription of the anthranilate synthase gene upon induction in the
      double line (TDC+ASalpha) and in vitro enzyme assays confirmed increased
      resistance to feedback inhibition by tryptophan. In TDC enzyme assays, increases
      of 48% and 87% in the TDC and double lines, respectively, were noted. Although
      the TDC line showed no significant increase in tryptamine levels on induction,
      induction of the double line resulted in increases in tryptamine levels of as
      much as six-fold for a 3 day late exponential induction. Downstream effects on
      alkaloids were noted in the TDC line where serpentine specific yields increased
      as much as 129% on induction. No effects on measured alkaloids were noted in the
      double line, but the two clones have very different basal alkaloid biosynthetic
      capacities. Within this study, the engineering of the indole pathway in C. roseus
      hairy roots is reported, and the role of the indole pathway in alkaloid
      biosynthesis explored.

PMID- 15491857
TI  - The phosphoenolpyruvate carboxykinase also catalyzes C3 carboxylation at the
      interface of glycolysis and the TCA cycle of Bacillus subtilis.
AB  - Quantitative physiological characterization and isotopic tracer experiments
      revealed that pyruvate kinase mutants of Bacillus subtilis produced significantly
      more CO(2) from glucose in the tricarboxylic acid cycle than is explained by the
      remaining conversion of phosphoenolpyruvate (PEP) to pyruvate catalyzed by the
      phosphotransferase system. We show here that this additional catabolic flux into
      the tricarboxylic acid cycle was catalyzed by the PEP carboxykinase. In contrast
      to its normal role in gluconeogenesis, PEP carboxykinase can operate in the
      reverse direction from PEP to oxaloacetate upon knockout of pyruvate kinase in a
      riboflavin-producing B. subtilis strain and in wild-type 168. At least in the
      industrial strain, we demonstrate the additional capacity of PEP carboxykinase to
      function as a substitute anaplerotic reaction when the normal pyruvate
      carboxylase is inactivated. Presumably as a consequence of the unfavorable
      kinetics of an ATP-synthesizing anaplerotic PEP carboxykinase reaction, such
      pyruvate carboxylase mutants grow slowly or, as in the case of wild-type 168, not
      at all.

PMID- 15491858
TI  - Integration of gene expression data into genome-scale metabolic models.
AB  - A framework for integration of transcriptome data into stoichiometric metabolic
      models to obtain improved flux predictions is presented. The key idea is to
      exploit the regulatory information in the expression data to give additional
      constraints on the metabolic fluxes in the model. Measurements of gene expression
      from chemostat and batch cultures of Saccharomyces cerevisiae were combined with
      a recently developed genome-scale model, and the computed metabolic flux
      distributions were compared to experimental values from carbon labeling
      experiments and metabolic network analysis. The integration of expression data
      resulted in improved predictions of metabolic behavior in batch cultures,
      enabling quantitative predictions of exchange fluxes as well as qualitative
      estimations of changes in intracellular fluxes. A critical discussion of
      correlation between gene expression and metabolic fluxes is given.

PMID- 15491859
TI  - Applicability of CoA/acetyl-CoA manipulation system to enhance isoamyl acetate
      production in Escherichia coli.
AB  - Coenzyme A (CoA) and its thioester derivatives are important precursor molecules
      for many industrially useful compounds such as esters, PHBs, lycopene and
      polyketides. Previously, in our lab we could increase the intracellular levels of
      CoA and acetyl-Coenzyme A (acetyl-CoA) by overexpressing one of the upstream rate
      controlling enzymes pantothenate kinase with a concomitant supplementation of the
      precursor pantothenic acid to the cell culture medium. In this study, we showed
      that the CoA/acetyl-CoA manipulation system could be used to increase the
      productivity of industrially useful compounds derived from acetyl-CoA. We chose
      the production of isoamyl acetate as a model system. Isoamyl acetate is an
      important flavor component of sake yeast and holds a great commercial value.
      Alcohol acetyl transferase (AAT) condenses isoamyl alcohol and acetyl-CoA to
      produce isoamyl acetate. The gene ATF2, coding for this AAT was cloned and
      expressed in Escherichia coli. This genetic engineered E. coli produces isoamyl
      acetate, an ester, from intracellular acetyl-CoA when isoamyl alcohol is added
      externally to the cell culture medium. In the current study, we showed that in a
      strain bearing ATF2 gene, an increase in intracellular CoA/acetyl-CoA by
      overexpressing panK leads to an increase in isoamyl acetate production.
      Additionally, the cofactor manipulation technique was combined with more
      traditional approach of competing pathway deletions to further increase isoamyl
      acetate production. The acetate production pathway competes with isoamyl acetate
      production for the common intracellular metabolite acetyl-CoA. Earlier we have
      shown that acetate pathway deletion (ackA-pta) increases isoamyl acetate
      production. The acetate production pathway was inactivated under elevated
      CoA/acetyl-CoA conditions, which lead to a further increase in isoamyl acetate
      production.

PMID- 15491860
TI  - Engineering precursor flow for increased erythromycin production in Aeromicrobium
      erythreum.
AB  - Metabolic engineering technology for industrial microorganisms is under
      development to create rational, more reliable, and more cost-effective approaches
      to strain improvement. Strain improvement is a critical component of the drug
      development process, yet the genetic basis for high production by industrial
      microorganisms is still a mystery. In this study, a search was begun for genetic
      modifications critical for high-level antibiotic production. The model system
      used was erythromycin production studied in the unicellular actinomycete,
      Aeromicrobium erythreum. A tagged-mutagenesis approach allowed reverse
      engineering of improved strains, revealing two genes, mutB and cobA, in the
      primary metabolic branch for methylmalonyl-CoA utilization. Knockouts in these
      genes created a permanent metabolic switch in the flow of methylmalonyl-CoA, from
      the primary branch into a secondary metabolic branch, driving erythromycin
      overproduction. The model provides insights into the regulation and evolution of
      secondary metabolism.

PMID- 15491861
TI  - Metabolic flux analysis for calcium dependent antibiotic (CDA) production in
      Streptomyces coelicolor.
AB  - The calcium dependent antibiotic (CDA) is a nonribosomal lipopeptide produced by
      Streptomyces coelicolor. We constructed a metabolic network of more than 400
      reactions for the primary and secondary metabolism of S. coelicolor and used
      computational metabolic flux balancing to investigate some of the factors
      affecting growth and production of CDA. Computational results indicated that the
      CDA production was concomitant with growth. Computational specific growth rates
      were twice as high as the experimental specific growth rates. Metabolic flux
      distributions and sensitivity analyses computed for various phases of the batch
      culture indicated that the specific CDA production rate was affected by nitrogen
      assimilation, pentose phosphate pathway, shikimate biosynthesis, and oxoglutarate
      fluxes. Consequently, these metabolic targets were tested using genetic deletions
      in the model which increased the in silico specific CDA production rate.

PMID- 15491862
TI  - A Boolean algorithm for reconstructing the structure of regulatory networks.
AB  - Advances in transcriptional analysis offer great opportunities to delineate the
      structure and hierarchy of regulatory networks in biochemical systems. We present
      an approach based on Boolean analysis to reconstruct a set of parsimonious
      networks from gene disruption and over expression data. Our algorithms, Causal
      Predictor (CP) and Relaxed Causal Predictor (RCP) distinguish the direct and
      indirect causality relations from the non-causal interactions, thus significantly
      reducing the number of miss-predicted edges. The algorithms also yield
      substantially fewer plausible networks. This greatly reduces the number of
      experiments required to deduce a unique network from the plausible network
      structures. Computational simulations are presented to substantiate these
      results. The algorithms are also applied to reconstruct the entire network of
      galactose utilization pathway in Saccharomyces cerevisiae. These algorithms will
      greatly facilitate the elucidation of regulatory networks using large scale gene
      expression profile data.

PMID- 15491863
TI  - Metabolic network analysis on Phaffia rhodozyma yeast using 13C-labeled glucose
      and gas chromatography-mass spectrometry.
AB  - Carotenoid production by microorganisms, as opposed to chemical synthesis, could
      fulfill an ever-increasing demand for 'all natural' products. The yeast Phaffia
      rhodozyma has received considerable attention because it produces the red pigment
      astaxanthin, commonly used as an animal feed supplement. In order to have a
      better understanding of its metabolism, labeling experiments with [1
      (13)C]glucose were conducted with the wildtype strain (CBS5905T) and a hyper
      producing carotenoid strain (J4-3) in order to determine their metabolic network
      structure and estimate intracellular fluxes. Amino acid labeling patterns, as
      determined by GC-MS, were in accordance with a metabolic network consisting of
      the Embden-Meyerhof-Parnas pathway, the pentose phosphate pathway, and the TCA
      cycle. Glucose was mainly consumed along the pentose phosphate pathway (
      approximately 65% for wildtype strain), which reflected high NADPH requirements
      for lipid biosynthesis. Although common to other oleaginous yeast, there was no,
      or very little, malic enzyme activity for carbon-limited growth. In addition,
      there was no evidence of phosphoketolase activity. The central carbon metabolism
      of the mutant strain was similar to that of the wildtype strain, though the
      relative pentose phosphate flux was lower and the TCA cycle flux in accordance
      with the biomass yield being lower.

PMID- 15491864
TI  - Manipulation of malic enzyme in Saccharomyces cerevisiae for increasing NADPH
      production capacity aerobically in different cellular compartments.
AB  - The yeast Saccharomyces cerevisiae is an attractive cell factory, but in many
      cases there are constraints related with balancing the formation and consumption
      of redox cofactors. In this work, we studied the effect of having an additional
      source of NADPH in the cell. In order to do this, two strains were engineered by
      overexpression of malic enzyme. In one of them, malic enzyme was overexpressed as
      its wild-type mitochondrial form, and in the other strain a short form lacking
      the mitochondrial targeting sequence was overexpressed. The recombinant strains
      were analyzed in aerobic batch and continuous cultivations, and the basic growth
      characteristics were generally not affected to a great extent, even though
      pleiotropic effects of the manipulations could be seen by the altered in vitro
      activities of selected enzymes of the central metabolism. Moreover, the decreased
      pentose-phosphate pathway flux and the ratios of redox cofactors showed that a
      net transhydrogenase effect was obtained, which can be directed to the cytosol or
      the mitochondria. This may find application in redirecting fluxes for improving
      specific biotechnological applications.

PMID- 15491865
TI  - Metabolic design based on a coupled gene expression-metabolic network model of
      tryptophan production in Escherichia coli.
AB  - The presumably high potential of a holistic design approach for complex
      biochemical reaction networks is exemplified here for the network of tryptophan
      biosynthesis from glucose, a system whose components have been investigated
      thoroughly before. A dynamic model that combines the behavior of the trp operon
      gene expression with the metabolic network of central carbon metabolism and
      tryptophan biosynthesis is investigated. This model is analyzed in terms of
      metabolic fluxes, metabolic control, and nonlinear optimization. We compare two
      models for a wild-type strain and another model for a tryptophan producer. An
      integrated optimization of the whole network leads to a significant increase in
      tryptophan production rate for all systems under study. This enhancement is well
      above the increase that can be achieved by an optimization of subsystems. A
      constant ratio of control coefficients on tryptophan synthesis rate has been
      identified for the models regarding or disregarding trp operon expression.
      Although we found some examples where flux control coefficients even contradict
      the trends of enzyme activity changes in an optimized profile, flux control can
      be used as an indication for enzymes that have to be taken into account in
      optimization.

PMID- 15491866
TI  - Optimal re-design of primary metabolism in Escherichia coli using linlog
      kinetics.
AB  - This paper examines the validity of the linlog approach, which was recently
      developed in our laboratory, by comparison of two different kinetic models for
      the metabolic network of Escherichia coli. The first model is a complete
      mechanistic model; the second is an approximative model in which linlog kinetics
      are applied. The parameters of the linlog model (elasticities) are derived from
      the mechanistic model. Three different optimization cases are examined. In all
      cases, the objective is to calculate the enzyme levels that maximize a certain
      flux while keeping the total amount of enzyme constant and preventing large
      changes of metabolite concentrations. For an average variation of metabolite
      levels of 10% and individual changes of a factor 2, the predicted enzyme levels,
      metabolite concentrations and fluxes of both models are highly similar. This
      similarity holds for changes in enzyme level of a factor 4-6 and for changes in
      fluxes up to a factor 6. In all three cases, the predicted optimal enzyme levels
      could neither have been found by intuition-based approaches, nor on basis of flux
      control coefficients. This demonstrates that kinetic models are essential tools
      in Metabolic Engineering. In this respect, the linlog approach is a valuable
      extension of MCA, since it allows construction of kinetic models, based on MCA
      parameters, that can be used for constrained optimization problems and are valid
      for large changes of metabolite and enzyme levels.

PMID- 15491867
TI  - Metabolic flux control analysis of branch points: an improved approach to obtain
      flux control coefficients from large perturbation data.
AB  - An overview of published approaches for the metabolic flux control analysis of
      branch points revealed that often not all fundamental constraints on the flux
      control coefficients have been taken into account. This has led to contradictory
      statements in literature on the minimum number of large perturbation experiments
      required to estimate the complete set of flux control coefficients C(J) for a
      metabolic branch point. An improved calculation procedure, based on approximate
      Lin-log reaction kinetics, is proposed, providing explicit analytical solutions
      of steady state fluxes and metabolite concentrations as a function of large
      changes in enzyme levels. The obtained solutions allow direct calculation of
      elasticity ratios from experimental data and subsequently all C(J)-values from
      the unique relation between elasticity ratio's and flux control coefficients.
      This procedure ensures that the obtained C(J)-values satisfy all fundamental
      constraints. From these it follows that for a three enzyme branch point only one
      characterised or two uncharacterised large flux perturbations are sufficient to
      obtain all C(J)- values. The improved calculation procedure is illustrated with
      four experimental cases.

PMID- 15491868
TI  - Could smallpox come back?

PMID- 15491869
TI  - Smallpox: a disease and a weapon.

PMID- 15491870
TI  - Addressing the concerns about smallpox.

PMID- 15491871
TI  - Smallpox containment updated: considerations for the 21st century.
AB  - The emergence and re-emergence of infectious diseases since the eradication of
      smallpox has had a direct impact on preparedness for a deliberately-caused
      smallpox outbreak, should one occur. The emergence of HIV has placed restrictions
      on the safe and effective use of smallpox vaccines and made the need for vaccinia
      immune globulin important for outbreak control. At the same time, the threat of
      international spread of emerging and re-emerging infections has prompted global
      investments in surveillance and response mechanisms such as the Global Outbreak
      Alert and Response Network (GOARN), a mechanism that would enhance the world's
      collaboration in smallpox containment as it did during the recent outbreak of
      SARS. Though global preparedness for a deliberately-caused smallpox outbreak has
      increased with the creation of GOARN, it does not replace the need for increased
      national public health investment to expand surge capacity for the management of
      patients and their contacts and to strengthen emergency communication networks to
      ensure effective response.

PMID- 15491872
TI  - Policies in place throughout the world: action by the European Union.

PMID- 15491873
TI  - ACAM2000 clonal Vero cell culture vaccinia virus (New York City Board of Health
      strain)--a second-generation smallpox vaccine for biological defense.
AB  - The threat of smallpox as a biological weapon has spurred efforts to create
      stockpiles of vaccine for emergency preparedness. In lieu of preparing vaccine in
      animal skin (the original method), we cloned vaccinia virus (New York City Board
      of Health strain, Dryvax by plaque purification and amplified the clone in cell
      culture. The overarching goal was to produce a modern vaccine that was equivalent
      to the currently licensed Dryvax in its preclinical and clinical properties, and
      could thus reliably protect humans against smallpox. A variety of clones were
      evaluated, and many were unacceptably virulent in animal models. One clonal virus
      (ACAM1000) was selected and produced at clinical grade in MRC-5 human diploid
      cells. ACAM1000 was comparable to Dryvax in immunogenicity and protective
      activity but was less neurovirulent for mice and nonhuman primates. To meet
      requirements for large quantities of vaccine after the events of September 11th
      2001, the ACAM1000 master virus seed was used to prepare vaccine (designated
      ACAM2000) at large scale in Vero cells under serum-free conditions. The genomes
      of ACAM1000 and ACAM2000 had identical nucleotide sequences, and the vaccines had
      comparable biological phenotypes. ACAM1000 and ACAM2000 were evaluated in three
      Phase 1 clinical trials. The vaccines produced major cutaneous reactions and
      evoked neutralizing antibody and cell-mediated immune responses in the vast
      majority of subjects and had a reactogenicity profile similar to that of Dryvax.

PMID- 15491874
TI  - Enhancing sonochemical activity in aqueous media using power-modulated pulsed
      ultrasound: an initial study.
AB  - Relatively little is known about the effects of pulsed ultrasound on the
      facilitation of chemical reactivity. Previous studies have indicated that
      sonochemistry using pulses is generally less effective than continuous ultrasonic
      irradiation. However, the pulse trains employed were such that the peak power of
      the pulses was the same as the maximum power used in continuous irradiation. As a
      result, less acoustic energy was transmitted to the solutions over the same
      period of time. The effectiveness of ultrasound when the pulse is adjusted so
      that the same amount of acoustic energy is input compared to continuous
      irradiation over a given time has not been previously explored. In this study we
      have embarked on an examination of the efficacy of power-modulated pulsed (PMP)
      sonochemistry. Specifically, we have explored the effects of pulse type and pulse
      frequency on the oxidation of potassium iodide and the degradation of acid
      orange, a common industrial colorant. A rate increase by a factor of three was
      observed compared with continuous irradiation under conditions of equivalent
      acoustic input power.

PMID- 15491875
TI  - Factors influencing the ultrasonic separation of oil-in-water emulsions.
AB  - Ultrasound may have inherent shortcomings that preclude its ability to coagulate
      grease from wastewater, yet these may be overcome by the simultaneous application
      of electrolysis. We studied the role of pH, conductivity, temperature, ultrasound
      intensity and duration, and electrolysis voltage, current, and duration, in the
      study treatment. Conductivity was found to be the most significant factor,
      however interactions among the eight study variables are likely more important
      than individual factors. The proposed process was capable of removing up to 100%
      of grease from the studied wastewater.

PMID- 15491876
TI  - Ultrasound-promoted alkynylation of ethynylbenzene to ketones under solvent-free
      condition.
AB  - This paper described alkynylation of ethynylbenzene to ketones catalyzed by
      potassium tert-butoxide under solvent-free conditions in the presence of
      ultrasound irradiation.

PMID- 15491877
TI  - Sonochemical one-directional growth of montmorillonite-polystyrene nanocomposite.
AB  - Montmorillonite-exfoliated polystyrene (MMT-PS) nanocomposite was one-pot
      synthesized by high-intensity ultrasonic irradiation. Moreover, the MMT-PS
      exhibited one-directional growth during the sonication.

PMID- 15491878
TI  - Efficient and mild room temperature reduction of benzophenones under ultrasound
      irradiation.
AB  - Benzophenones without strong electron-releasing substituents were reduced into
      the corresponding benzhydrols at room temperature in moderate to good yields with
      Zn-NaOH-95% ethanol under ultrasound irradiation. This method is also propitious
      to the synthesis of 3-phenylphthalide and its derivates.

PMID- 15491879
TI  - Sonochemistry in China between 1997 and 2002.
AB  - This is a review with 91 references to introduce the studies involving
      sonochemistry published by Chinese scientists between 1997 and 2002.

PMID- 15491880
TI  - Mechanochemical degradation kinetics of high-density polyethylene melt and its
      mechanism in the presence of ultrasonic irradiation.
AB  - In this paper, the effect of ultrasonic intensity on the degradation of high
      density polyethylene (HDPE) melt, degradation mechanism, ultrasonic degradation
      kinetics of HDPE melt as well as the development of molecular weight distribution
      of HDPE melt during ultrasonic degradation were studied. In the initial stage,
      the ultrasonic degradation of HDPE melt shows a random scission process, and the
      molecular weight distribution broadens. After that, the ultrasonic degradation of
      HDPE melt shows a nonrandom scission process, and the molecular weight
      distribution of HDPE melt narrows with ultrasonic irradiation time. The average
      molecular weight of HDPE decreases with the increase of ultrasonic intensity and
      increases and trends forward that of undegraded HDPE with the increase of
      distance from ultrasonic probe tip, indicating that attenuation of ultrasonic
      intensity in HDPE melt is very quick. Ultrasonic degradation kinetics of HDPE
      melt obeys the equation: Mt=M(infinity) + Ae(-kt). The theoretic calculation by
      this equation accords well with the experimental results. The plausible
      ultrasonic degradation mechanism of polymer melt based on molecular relaxation
      was also proposed in this paper.

PMID- 15491881
TI  - Sonochemical preparation of composite nanoparticles of Au/gamma-Fe2O3 and
      magnetic separation of glutathione.
AB  - We prepared Au/gamma-Fe2O3 composite nanoparticles by sonochemically reducing
      Au(III) ions employing no stabilizer in the aqueous solution to form stable Au
      nanoparticles and allowing them to attach onto the surface of gamma-Fe2O3
      particles with an average size of 21 nm. Size of the formed Au nanoparticle
      depended on the initial concentration of Au(III) ions. The number of the Au
      nanoparticles, supported on each gamma-Fe2O3 particle was controlled by changing
      the relative amounts of Au(III) ions and gamma-Fe2O3 particles. The composite
      nanoparticles exhibited a high affinity with glutathione, a tripeptide with
      mercapto group so that separation and manipulation of glutathione in aqueous
      solutions could be performed by application of external magnetic field. Because
      the surfaces of the Au nanoparticles were not shielded by any stabilizers, or
      naked, sonochemically prepared Au/gamma-Fe2O3 composite nanoparticles seemed to
      show stronger affinity to the glutathione than those by the radiochemical method.

PMID- 15491882
TI  - Complete mineralization of propyzamide in aqueous solution containing TiO2
      particles and H2O2 by the simultaneous irradiation of light and ultrasonic waves.
AB  - Environmental problems arise from the pollution of ground water and soil by
      propyzamide, 3,5-dichloro-N-(3-methyl-1-butyn-3-yl) benzamide, which is a popular
      herbicide. To decompose propyzamide, aqueous solutions containing propyzamide and
      TiO2 particles was irradiated by light. The photocatalytic decomposition was
      accelerated when the solution temperature and pH were high. The temperature
      dependence was due to the adsorption processes of propyzamide on the TiO2
      particles. The decomposition was further promoted by addition of H2O2 because of
      its effective electron-trapping and generated *OH which was available to
      decompose propyzamide. Although no propyzamide was detected in the solution after
      the irradiation time of about 20 min, the decomposed intermediate compounds still
      remained. In order to mineralize completely propyzamide, simultaneous irradiation
      by light and ultrasonic waves was carried out. The hybrid effect of the
      irradiation by light and ultrasonic waves in conjunction with H2O2 was first
      confirmed to achieve the complete mineralization of propyzamide.

PMID- 15491883
TI  - Preparation of stable porous nickel and cobalt oxides using simple inorganic
      precursor, instead of alkoxides, by a sonochemical technique.
AB  - Porous nickel and cobalt oxides were prepared using NiSO4.6H2O and anhydrous
      Co(CH3COO)2, a precursor other than alkoxides and cetyltrimethylammonium bromide
      as organic surfactant. The sonication method has been used for such synthesis.
      The surfactants were removed by calcination, as well as by solvent extraction and
      it is extent was examined by IR spectroscopy. The trend of removal of surfactant
      was followed by TGA studies and the change in phases by DSC. The products were
      identified by XRD. Peak in low angle XRD indicates the porous nature of the
      oxides. The morphology of the pores was studied by transmission electron
      microscopy. The pores were found less ordered, having an average size of 4-6 nm.
      The Brunauer-Emmet-Teller surface areas of the as-prepared, as well as the
      treated samples are reported having H2 and H4 type hysteresis for Ni and Co,
      respectively.

PMID- 15491884
TI  - An improved sonochemical reactor.
AB  - The design and optimization of sonochemical apparatus are still open to
      advancement. Under high-intensity ultrasound reaction rates and yields are mainly
      influenced by the characteristics of transducer and reactor. Several useful
      improvements are introduced and described. In order to achieve uniformity of the
      acoustic field and optimal acoustic streaming in every part of the reaction
      vessel (a Teflon tube), the reactor can be made to rotate eccentrically around
      the horn axis and the probe to move alternatively up and down by a pre-determined
      excursion at a chosen speed. Continuous high-power irradiation is feasible
      without any time limit because the whole probe system is refrigerated by an oil
      forced-circulation circuit connected to a chiller. The apparatus can control a
      number of important reaction parameters: modified atmosphere, reaction
      temperature, tunable frequency and constant amplitude. Excellent performance was
      observed on several reactions, such as the chemical modification of chitosan, a
      poorly soluble biopolymer.

PMID- 15491885
TI  - Effect of ultrasound on activation of serine proteases precursors.
AB  - The effect of ultrasound (US) (26.4 kHz, 26 W/cm2) on the activation process of a
      mixture of chymotrypsinogen and trypsinogen was studied. US led to a significant
      decrease in proteolytic activity, as well as inhibition of the activation process
      in general. It was shown that inhibition of proteinase activity under US
      influence was a consequence of inhibition of chymotrypsinogen-chymotrypsin
      transformation and the complete proteolytic trypsin degradation in the proenzymes
      mixture.

PMID- 15491886
TI  - Discussion of parameters associated with the ultrasonic solid-liquid extraction
      for elemental analysis (total content) by electrothermal atomic absorption
      spectrometry. An overview.
AB  - Ultrasonic solid-liquid extraction (USLE) of trace metals from biological and
      environmental samples and its subsequent quantification by electrothermal atomic
      absorption spectrometry (ET-AAS) is nowadays an emerging methodology in the
      analytical laboratory. However, this methodology is far from maturity as can be
      readily demonstrated from the controversial data reported by different workers.
      In the light of our own experience and a survey of published data, a general
      approach for USLE-ET-AAS is discussed, taking into account the different
      variables which affect ultrasonic solid-liquid extraction, namely, the ultrasonic
      device chosen for ultrasonic extraction (e.g. ultrasonic bath or ultrasonic
      probe), particle size, acid concentration, sonication time and sonication
      amplitude, sample mass and analyte-matrix binding.

PMID- 15491887
TI  - A study to determine whether cavitation occurs around dental ultrasonic scaling
      instruments.
AB  - The aim of this investigation was to determine if cavitation occurred around
      dental ultrasonic scalers and to estimate the amount of cavitation occurring.
      Three styles of tip (3 x TFI-10, 3 x TFI-3, 3 x TFI-1) were used, in conjunction
      with a Cavitron SPS ultrasonic generator (Dentsply, USA), to insonate
      terephthalic acid solution. The hydroxyl radical, [*OH], concentration, produced
      due to cavitation from the scaler tips, was monitored by fluorescence
      spectroscopy. Cavitational activity was enhanced at higher power settings and at
      longer operating times. The tip dimensions and geometry as well as the generator
      power setting are both important factors that affect the production of
      cavitation.

PMID- 15491888
TI  - Leaching of silver from solid waste using ultrasound assisted thiourea method.
AB  - Thiourea leaching of precious metals such as gold and silver from ores has
      several advantages when compared with conventional cyanidation process. In recent
      years, the use of ultrasound in leaching processes is becoming increasingly
      popular in hydrometallurgy. This paper deals with combining these two techniques
      for silver leaching from solid waste of a cyanidation leach plant located in
      Kutahya, Turkey. The primary aim of this research is to assess the technical
      performance of the method. To achieve maximum leaching yield, eight process
      variables have been selected to estimate optimum process conditions by means of
      statistical factorial design and steepest ascent techniques. Laboratory-scale
      experiments showed that complete leaching of silver may be achieved by this
      process.

PMID- 15491889
TI  - The geography of health knowledge/s.

PMID- 15491890
TI  - Conceptualising geographies of health knowledge: the emergence of new education
      spaces for public health.
AB  - In recent years both new knowledges and new experts have been introduced into
      public health as part of the development of multidisciplinary practice. This
      paper presents an analysis of these recent changes, which is informed by
      theoretical ideas around governmentality and geographies of knowledge. Although
      critical geographies of public health are starting to emerge the education of
      professionals, specifically the production and consumption of knowledges within
      education spaces, remains relatively unexplored. This research extends existing
      work by critically examining the academic instruction of professionals through
      the Masters in Public Health programmes. Specifically the paper argues that new
      spaces of education are emerging to meet the requirements of multidisciplinary
      practice, however there is no blueprint. Instead a geographically based diversity
      of practice can be observed which is characterised by enclosures of expertise
      wherein competing forms of public health knowledge and expert are held as ideal.

PMID- 15491891
TI  - Spaces and networks of genetic knowledge making: the 'geneticisation' of heart
      disease.
AB  - The 'geneticisation' of health, medicine and the body is extending from single
      gene to multi-factorial conditions such as heart disease. Adopting 'Actor Network
      Theory', the paper argues that the making of genetic knowledge occurs in spaces
      and networks where contested knowledges necessarily produce a geneticisation that
      is neither certain nor complete. Drawing on empirical research in a coronary care
      unit in Glasgow, Scotland, the paper sets out the network of consultants,
      rehabilitation nurses and people with heart disease and others who collectively,
      through contestation and the marshalling of knowledges by prominent social
      actors, produce an understanding of the role of genes in heart disease.

PMID- 15491892
TI  - "A double-edged sword"? The professionalisation of counselling in the United
      Kingdom.
AB  - Drawing on interviews with practitioners involved in voluntary-sector counselling
      in Scotland, this paper explores contradictions associated with the
      professionalisation of counselling in the UK. Five meanings of the term
      "professional" are identified. Those in support of professionalisation aim to
      bring these different meanings into close alignment, whereas those with
      reservations point to tensions between at least some of these meanings and core
      values of counselling. In conclusion the paper reflects on the possibility that
      counselling might contribute to a reshaping of what it means to be a profession.

PMID- 15491893
TI  - No alternative? The regulation and professionalization of complementary and
      alternative medicine in the United Kingdom.
AB  - In conjunction with its growing popularity, complementary and alternative
      medicine (CAM) in the United Kingdom has witnessed increasing
      professionalization, partly prompted by the landmark Parliamentary Inquiry that
      reported in November 2000. Professionalization has become a significant strategy
      for practitioner associations and a key focus for the government, media, and
      patient groups. It is being driven by concern over the interests of patients and
      consumers, and in relation to the possible integration of certain forms of CAM
      into publicly funded healthcare. It is, moreover, being reconfigured in
      explicitly national terms. This paper draws on research into practitioner
      associations representing nine CAM modalities in the UK-aromatherapy, Chinese
      herbal medicine, chiropractic, crystal healing, feng shui, 'lay' homeopathy,
      medical homeopathy, osteopathy, and Radionics-, examining the recent wave of
      professionalization in relation to Foucault's concern with 'techniques of the
      self.' It highlights the contrasting experience of an association of Chinese
      herbalists seeking statutory self-regulation (SSR) and an association of
      chiropractors that was instrumental in securing SSR for chiropractic.

PMID- 15491894
TI  - Rationalising public participation in the health service: the case of research
      ethics committees.
AB  - This paper seeks to raise questions about the growing emphasis on public
      participation in decision-making in the health service. It examines the case
      study of lay participation on Local Research Ethics Committees (LRECs'). In the
      light of contested theoretical conceptions of the value of lay participation and
      an absence of a centrally defined role this paper examines practice. It uses
      qualitative evidence collected in 45 semi-structured interviews with committee
      members and observations of twenty committee meetings. It examines members' own
      conceptualisations of lay involvement and the contributions they are able to make
      in meetings as a result of these conceptualisations. It concludes that without
      better-defined roles for lay members on these committees they do not possess the
      authority or knowledge to challenge the experts' technical rendering of research.

PMID- 15491895
TI  - Challenging the 'view from nowhere': citizen reflections on specialist expertise
      in a deliberative process.
AB  - This paper presents analysis of citizen encounters with specialists in a
      deliberative process, called Deliberative Mapping, which explored options for
      addressing the shortage of organs for transplantation in the UK. There is a rich
      theoretical literature about the extent to which citizens are competent to
      question the knowledge claims of specialists in complex decision-making
      processes, suggesting the trustworthiness of scientific expertise will depend on
      the qualities of social interaction in face-to-face dialogue, but little
      empirical analysis of specific encounters. This paper presents evidence of how
      citizens located specialist expertise in making judgements about the legitimacy
      and credibility of specialist knowledge claims, in ways that reflect differences
      in epistemic procedures valued by the panels of men and women in this process.

PMID- 15491896
TI  - Small area variations in infant mortality in England and Wales in the inter-war
      period and their link with socio-economic factors.
AB  - This paper considers the changing spatial pattern of infant mortality during the
      inter-war years (1921-1936) at Local Government District level in England and
      Wales. As well as vital statistics data for these areas, also available are 1921
      and 1931 Census data on unemployment, housing, occupational structure and
      population density, with additional data on unemployment from 1927 to 1936 for
      the 62 counties in which Districts are located. The statistical analysis relating
      changing District mortality to these characteristics derives mortality gradients
      across categorical forms of the social indicators, and assesses impacts of model
      re-specification to allow for spatio-temporal correlation. Time varying gradients
      across unemployment, housing and policy status are then investigated with a view
      to assessing whether there was a widening in mortality inequalities in the
      regionalized economic depression of the 1930s.

PMID- 15491897
TI  - Social capital and health among the aged: comparisons between the United States
      and Germany.
AB  - Through a cross-national investigation of the United States and Germany, this
      study examines how individual level social capital relates to the health of the
      elderly. Data from two national telephone surveys conducted in Germany (N=682)
      and the United States (N=608) with probability samples of non-institutionalized
      persons aged 60 and older was used. Indicators of social capital including both
      norms (reciprocity and civic trust) and behaviors (participation) were tested
      with three self-reported health indicators-overall health, depression (CES-D) and
      functional limitations. Housing variables and social support were controlled for
      in the study. Lack of reciprocity was associated with poorer self-rated health in
      both countries. Civic mistrust was associated with poorer self-rated health in
      both countries as well as with depression and functional limitations in America.
      Lack of participation was, in Germany, associated with poorer self-rated health
      and depression. The cross-national results indicate that individual-level
      analysis of social capital along with marco-level determinants are important for
      understanding the health of the elderly.

PMID- 15491898
TI  - Childhood obesity in China.

PMID- 15491899
TI  - Word learning in dogs?
AB  - In a recent paper, Kaminski, Call and Fischer report pioneering research on word
      learning in a dog. In this commentary we suggest ways of distinguishing
      referential word use from mere association. We question whether the dog is
      reasoning by exclusion and, if so, compare three explanations - learned
      heuristics, default assumptions, and pragmatic reasoning - as they apply to
      children and might apply to dogs. Kaminski et al.'s work clearly raises important
      questions about the origins and basis of word learning and social cognition.

PMID- 15491901
TI  - Why do we need a philosophy of the brain?

PMID- 15491902
TI  - Cognitive neural prosthetics.
AB  - Research on neural prosthetics has focused largely on using activity related to
      hand trajectories recorded from motor cortical areas. An interesting question
      revolves around what other signals might be read out from the brain and used for
      neural prosthetic applications. Recent studies indicate that goals and expected
      value are among the high-level cognitive signals that can be used and will
      potentially enhance the ability of paralyzed patients to communicate with the
      outside world. Other new findings show that local field potentials provide an
      excellent source of information about the cognitive state of the subject and are
      much easier to record and maintain than spike activity. Finally, new movable
      probe technologies will enable recording electrodes to seek out automatically the
      best signals for decoding cognitive variables.

PMID- 15491903
TI  - Event files: feature binding in and across perception and action.
AB  - The primate brain codes perceived events in a distributed fashion, which raises
      the question of how the codes referring to the same event are related to each
      other. Recent findings suggest that they are integrated into 'object files',
      episodic bindings of object-related information. However, the problem of
      integrating distributed codes is not restricted to perception but applies to
      action planning and sensorimotor processing as well. Here I argue that the brain
      addresses these problems by creating multi-layered networks of bindings - 'event
      files' - that temporarily link codes of perceptual events, the current task
      context, and the actions performed therein. These bindings produce systematic but
      often surprising and counter-intuitive interactions between, and impairments in,
      perception and action planning.

PMID- 15491904
TI  - Demystifying social cognition: a Hebbian perspective.
AB  - For humans and monkeys, understanding the actions of others is central to
      survival. Here we review the physiological properties of three cortical areas
      involved in this capacity: the STS, PF and F5. Based on the anatomical
      connections of these areas, and the Hebbian learning rule, we propose a simple
      but powerful account of how the monkey brain can learn to understand the actions
      of others by associating them with self-produced actions, at the same time
      discriminating its own actions from those of others. As this system appears also
      to exist in man, this network model can provide a framework for understanding
      human social perception.

PMID- 15491905
TI  - Thought before language.
AB  - To learn language infants must develop a conceptual base onto which language can
      be mapped. Recent research in infant cognitive development shows that at least by
      9 months of age infants have developed a conceptual system sufficiently rich to
      allow language to begin. Evidence for this system is shown by categorization of
      objects above and beyond their perceptual appearance, problem-solving, long-term
      recall of events, and inductive inferences. During the next year, early concepts
      gradually become refined. However, at the time when language takes off they are
      often still less specific than many words in daily use, accounting for the
      phenomenon of overextension of word meaning.

PMID- 15491906
TI  - Folk concepts and intuitions: from philosophy to cognitive science.
AB  - Analytic philosophers have long used a priori methods to characterize folk
      concepts such as knowledge, belief and wrongness. Recently, researchers have
      begun to exploit social scientific methodologies to characterize such folk
      concepts. One line of work has explored folk intuitions with cases that are
      disputed within philosophy. A second approach, with potentially more radical
      implications, applies the methods of cross-cultural psychology to philosophical
      intuitions. Recent work in this area suggests that people in different cultures
      have systematically different intuitions surrounding folk concepts. A third
      strand of research explores the emergence and character of folk concepts in
      children. These approaches to characterizing folk concepts provide important
      resources that will supplement, and perhaps in some cases displace, a priori
      approaches.

PMID- 15491908
TI  - Plant nuclear bodies.
AB  - Knowledge of the organization of transcription, RNA processing and transport, and
      the assembly of complexes such as the ribosome, spliceosome and other RNPs is
      essential to understanding gene expression. Over several years, the nucleolus and
      Cajal bodies have been examined in plants, and recently, various other sub
      nuclear domains that are involved in RNA metabolism and hormonal responses have
      been discovered. These novel domains illustrate the complexity and subtlety of
      expression control and herald a new era of research on the molecular and cell
      biology of plant nuclei.

PMID- 15491909
TI  - Plastid-to-nucleus signalling.
AB  - The function of the eukaryotic cell depends on the reciprocal interaction between
      its different compartments. Plastids emit signals that regulate nuclear gene
      expression to ensure the stoichiometric assembly of plastid protein complexes and
      to initiate macromolecular reorganisation in response to environmental cues. It
      is now clear that several different plastid processes produce signals that
      influence the expression of photosynthetic genes in the nucleus. The genome
      uncoupled (gun) mutants recently revealed one of the plastid signals, the
      chlorophyll intermediate Mg-protoporphyrinIX.

PMID- 15491910
TI  - Plant organelle positioning.
AB  - Correct positioning and active movement of organelles within cells are essential
      for cellular homeostasis and adaptation to external stresses. Unlike animal and
      fungal systems, plant organelle positioning has not yet been revealed at the
      molecular level. The recent development of organelle-targeting green fluorescent
      protein (GFP) constructs and genetic analyses using Arabidopsis thaliana have
      shed new light on the field of plant organelle positioning, which has been found
      to be regulated by mechanisms that are similar to and/or distinct from those used
      by animals and fungi.

PMID- 15491911
TI  - MAPs in plant cells: delineating microtubule growth dynamics and organization.
AB  - Microtubule-associated proteins (MAPs) serve a wide variety of functions, from
      constructing and maintaining the microtubule cytoskeleton to using this
      cytoskeleton to transport cargo and to tether molecules that are involved in
      numerous cellular processes. Throughout the cell cycle, distinct microtubule
      arrays carry out specific roles in cytokinesis, karyokinesis, and cell expansion.
      Recent findings have shed new light on the importance of MAPs in controlling
      microtubule growth dynamics as well as in cross-linking microtubules to
      facilitate the formation and function of these cytoskeletal arrays.

PMID- 15491912
TI  - The plasmodesmatal transport pathway for homeotic proteins, silencing signals and
      viruses.
AB  - Non-cell-autonomous signals in the form of microRNAs and transcription factors
      could have important developmental functions. Plasmodesmata (PD) form a
      cytoplasmic network throughout the plant body and provide the means of symplasmic
      cell-to-cell transport in plants. Homeodomain transcription factors, small RNA
      molecules and viral genomic information move selectively to adjacent cells via PD
      microchannels. Tissue-specific expression studies of non-cell-autonomous
      transcription factors and RNA molecules have confirmed that their intercellular
      transport is a highly regulated process, which depends on the tissue,
      developmental stage and nature of the transported macromolecule. We have known
      for some time that gene-silencing signals spread both locally from cell to cell
      and across long distances following the source to sink transition. Recent work
      has provided evidence that small single-stranded silencing-induced RNAs and
      microRNA molecules are present in the phloem transport system of different plant
      species. Further, recent evidence has confirmed that the transport of silencing
      RNA via PD is a regulated and active process, and that an amplification-relay
      mechanism is in place for the long-distance spread of silencing signals.

PMID- 15491913
TI  - Progress in understanding the role of microtubules in plant cells.
AB  - Microtubules have long been known to play a key role in plant cell morphogenesis,
      but just how they fulfill this function is unclear. Transverse microtubules have
      been thought to constrain the movement of cellulose synthase complexes in order
      to generate transverse microfibrils that are essential for elongation growth.
      Surprisingly, some recent studies demonstrate that organized cortical
      microtubules are not essential for maintaining or re-establishing transversely
      oriented cellulose microfibrils in expanding cells. At the same time, however,
      there is strong evidence that microtubules are intimately associated with
      cellulose synthesis activity, especially during secondary wall deposition. These
      apparently conflicting results provide important clues as to what microtubules do
      at the interface between the cell and its wall. I hypothesize that cellulose
      microfibril length is an important parameter of wall mechanics and suggest ways
      in which microtubule organization may influence microfibril length. This concept
      is in line with current evidence that links cellulose synthesis levels and
      microfibril orientation. Furthermore, in light of new evidence showing that a
      wide variety of proteins bind to microtubules, I raise the broader question of
      whether a major function of plant microtubules is in modulating signaling
      pathways as plants respond to sensory inputs from the environment.

PMID- 15491914
TI  - Cell cycle and differentiation.
AB  - The development of multicellular organisms relies on the temporal and spatial
      control of cell proliferation and cell growth. The relationship between cell
      cycle progression and development is complex and characterized by mutual
      dependencies. On the level of the individual cell, this interrelationship has
      implications for pattern formation and cell morphogenesis. On a supercellular
      level, this interrelationship affects meristem function and organ growth. Often,
      developmental signals not only direct cell-cycle progression but also set the
      frame for cell-cycle regulation by determining cell-type-specific cell-cycle
      modes. In other cases, however, cell-cycle progression appears to be required for
      the further differentiation of some cell types. There are also examples in which
      cell cycle and differentiation seem to be controlled at the same level and
      progress rather independently from each other or are linked by the same regulator
      or pathway. Furthermore, different relationships between cell cycle and
      differentiation can be combined in a succession of events during development,
      leading to complex developmental programs.

PMID- 15491915
TI  - Lipid function in plant cell polarity.
AB  - The establishment and maintenance of cell polarity play pivotal roles during
      plant development. During the past five years, proteins that are required for
      different aspects of plant cell polarity have been identified. However, the
      functions of lipids and their interactions with proteins that mediate polarity
      remained largely unaddressed. Recent genetic studies have discovered cell and
      tissue polarity mutants that have defects in sterol composition,
      glycosylphosphatidylinositol-anchored proteins, glycosylphosphatidylinositol
      biosynthesis and phospholipid signalling. Analyses of the affected gene products
      have provided a first glance at the roles of lipids in cell polarity signalling,
      as well as in the trafficking and anchoring of polar proteins.

PMID- 15491916
TI  - Cullin-containing E3 ubiquitin ligases in plant development.
AB  - In eukaryotes, the ubiquitin-proteasome system participates in the control of
      signal transduction events by selectively eliminating regulatory proteins. E3
      ubiquitin ligases specifically bind degradation substrates and mediate their poly
      ubiquitylation, a prerequisite for their degradation by the 26S proteasome. On
      the basis of the analysis of the Arabidopsis genome sequence, it is predicted
      that there are more than 1000 E3 ubiquitin ligases in plants. Several types of E3
      ubiquitin ligases have already been characterized in eukaryotes. Recently, some
      of these E3 enzymes have been implicated in specific plant signaling pathways.

PMID- 15491917
TI  - Funneling auxin action: specificity in signal transduction.
AB  - Auxin regulates a broad spectrum of developmental processes, mediating
      transcriptional regulation via protein degradation. The molecular mechanisms of
      auxin action are partially understood whereas the molecular basis for
      developmental specificity in auxin responses is currently unclear. Recent
      biochemical and chemical-genetics studies have narrowed the search for regulators
      in auxin signaling that act upstream of auxin-dependent protein degradation. The
      auxin response requires the degradation of Aux/IAA inhibitors, which causes
      interacting ARF transcription factors to be released to regulate target genes.
      There are many ARFs and Aux/IAA proteins in Arabidopsis, and recent genetic
      studies suggest that their cell-specific combinations may determine the various
      auxin responses in development.

PMID- 15491918
TI  - Small GTPases in vesicle trafficking.
AB  - Plant small GTPases belonging to the Rop, Arf, and Rab families are regulators of
      vesicle trafficking. Rop GTPases regulate actin dynamics and modulate H(2)O(2)
      production in polar cell growth and pathogen defence. A candidate Rop GDP to Rop
      GTP exchange factor (RopGEF) SPIKE1 is involved in the morphogenesis of leaf
      epidermal cells. The ArfGEF GNOM regulates the endosomal recycling of the PIN
      proteins, which are involved in polar auxin transport. Intracellular localisation
      of small GTPases and functional studies using dominant mutant versions of Arf and
      Rab GTPases are defining novel plant-specific membrane compartments, especially
      those that participate in endosomal vesicle trafficking.

PMID- 15491919
TI  - Membrane trafficking in plants: new discoveries and approaches.
AB  - The general organization and function of the endomembrane system is highly
      conserved in eukaryotic cells. In addition, increasing numbers of studies
      demonstrate that normal plant growth and development are dependent on specialized
      tissue and subcellular-specific components of the plant membrane trafficking
      machinery. New approaches, including chemical genomics and proteomics, will
      likely accelerate our understanding of the diverse functions of the plant
      endomembrane system.

PMID- 15491920
TI  - Light-regulated nuclear localization of phytochromes.
AB  - Phytochrome is a soluble protein that regulates various responses of plants to
      light. Not all but most of the phytochrome responses are accompanied by changes
      in the pattern of gene expression. Upon light activation, phytochrome is imported
      into the nucleus by the nuclear localization activity of the carboxy-terminal
      half of the molecule. In darkness, the amino-terminal chromophoric domain
      suppresses this activity to retain the molecule in the cytoplasm. In the nucleus,
      light-activated phytochrome forms speckles whose biological function remains
      unclear.

PMID- 15491921
TI  - Gravity sensing and signaling.
AB  - Gravitropism has attracted much attention from plant biologists. Recent studies
      have provided molecular evidence supporting two long-surviving hypotheses about
      the mechanism of gravitropism: the starch-statolith hypothesis and the Cholodney
      Went hypothesis. Amyloplast movement along the gravity vector within gravity
      sensing cells in the root and shoot is the most likely trigger of subsequent
      intracellular signaling. Several possible events leading from this signaling to
      differential auxin distribution within the sensing cells have been suggested
      recently.

PMID- 15491922
TI  - Plant heterotrimeric G protein function: insights from Arabidopsis and rice
      mutants.
AB  - Heterotrimeric G proteins have been implicated in a wide range of plant
      processes. These include responses to hormones, drought, and pathogens, and
      developmental events such as lateral root formation, hypocotyl elongation, hook
      opening, leaf expansion, and silique development. Results and concepts emerging
      from recent phenotypic analyses of G-protein component mutants in Arabidopsis and
      rice are adding to our understanding of G-protein mechanisms and functions in
      higher plants.

PMID- 15491923
TI  - Consistent over-estimation of gene number in complex plant genomes.
AB  - The first comprehensive comparison of gene content between higher plant species
      provided the unexpected conclusions that rice contained about twice as many genes
      as Arabidopsis, and that about half of the rice genes had no obvious homologs in
      any other organism. Our subsequent analyses indicate that most of these "extra,
      novel" rice genes are mis-annotated segments of transposable elements, especially
      retrotransposons. Aggressive annotation of a randomly selected subset of the rice
      genome suggests that the gene number is less than 40000. The five fantasies of
      automated plant gene discovery are described and a protocol is provided to
      minimize (or at least predict) the inaccuracy of future plant genome annotations.

PMID- 15491924
TI  - Molecular basis for the evolution of xylem lignification.
AB  - The lignification of xylem is an adaptive trait of great significance.
      Gymnosperms and angiosperms share an ancient, conserved set of enzymes that are
      regulated by a conserved transcription factor and that are responsible for the
      formation of guaiacyl lignin. Angiosperms have evolved at least two enzymes that
      catalyze the production of syringyl lignin. Association genetics is now being
      used to explore the adaptive significance of sequence variation in the genes that
      encode these monolignol biosynthetic enzymes.

PMID- 15491925
TI  - Can data from an electronic medical record identify which patients with pneumonia
      have Pneumocystis carinii Infection?
AB  - BACKGROUND: Pneumocystis carinii is the leading opportunistic pulmonary infection
      in HIV-infected patients. Invasive diagnostic procedures might be avoided if
      available electronic data can accurately identify patients with Pneumocystis
      pneumonia (PCP). METHODS: We extracted data from electronic hospital records,
      emergency department records, and a pathology database for 299 HIV-infected
      patients with pneumonia who underwent bronchoscopy. We identified independent
      indicators of confirmed PCP using logistic regression analysis on a random half
      of the patients and validated the predictive power of the resulting model on the
      other half. RESULTS: Bronchoscopy confirmed pneumocystis carinii in 111 patients
      (37%). Five of the seven significant independent predictors of PCP came from
      patients' electronic medical records: infiltrate on chest radiograph, male
      gender, lower red cell distribution width, lower serum creatinine, and a prior
      positive HIV test. The other two (duration of illness and presence of dyspnea)
      came from the emergency department record. A simple index found 43% of patients
      at low risk (18% with pneumocystis), 37% at moderate risk (36% with
      pneumocystis), and 20% at high risk (74% with pneumocystis). CONCLUSIONS: Data
      from electronic medical records can help quantify the risk of PCP among HIV
      infected patients. However, the model failed to identify 18% of patients with PCP
      in the low risk group, and empiric therapy would erroneously treat 26% of
      patients classified as high risk. Bronchoscopy is needed to accurately diagnose
      PCP among HIV-infected patients with pneumonia. However, if bronchoscopy is not
      available, the model can help with initial decisions about antibiotic therapy.

PMID- 15491926
TI  - Producing computer-generated tailored written information for stroke patients and
      their carers: system development and preliminary evaluation.
AB  - PURPOSE: The aim of this project was to design and evaluate a system that would
      produce tailored information for stroke patients and their carers, customised
      according to their informational needs, and facilitate communication between the
      patient and health professional. METHOD: A human factors development approach was
      used to develop a computer system, which dynamically compiles stroke education
      booklets for patients and carers. Patients and carers are able to select the
      topics about which they wish to receive information, the amount of information
      they want, and the font size of the printed booklet. The system is designed so
      that the health professional interacts with it, thereby providing opportunities
      for communication between the health professional and patient/carer at a number
      of points in time. RESULTS: Preliminary evaluation of the system by health
      professionals, patients and carers was positive. A randomised controlled trial
      that examines the effect of the system on patient and carer outcomes is underway.

PMID- 15491927
TI  - E-health in the East Asian tigers.
AB  - OBJECTIVE: The article analyzes e-health progress in East Asia's leading tiger
      economies: Japan, Hong Kong, Singapore, South Korea and Taiwan. It describes five
      main dimensions of e-health provision in the tigers: policymaking, regulation,
      provision, funding and physician-patient relations. METHODS: We conducted a
      series of fieldwork interviews and analyzed key healthcare websites. RESULTS AND
      CONCLUSION: Our main finding is that the development of e-health in the region is
      less advanced than might be expected. Our explanation focuses on institutional,
      cultural and financial factors.

PMID- 15491928
TI  - Heuristic evaluation of infusion pumps: implications for patient safety in
      Intensive Care Units.
AB  - OBJECTIVE: The goal of this research was to use a heuristic evaluation
      methodology to uncover design and interface deficiencies of infusion pumps that
      are currently in use in Intensive Care Units (ICUs). Because these infusion
      systems cannot be readily replaced due to lease agreements and large-scale
      institutional purchasing procedures, we argue that it is essential to
      systematically identify the existing usability problems so that the possible
      causes of errors can be better understood, passed on to the end-users (e.g.,
      critical care nurses), and used to make policy recommendations. DESIGN: Four
      raters conducted the heuristic evaluation of the three-channel infusion pump
      interface. Three raters had a cognitive science background as well as experience
      with the heuristic evaluation methodology. The fourth rater was a veteran
      critical care nurse who had extensive experience operating the pumps. The
      usability experts and the domain expert independently evaluated the user
      interface and physical design of the infusion pump and generated a list of
      heuristic violations based upon a set of 14 heuristics developed in previous
      research. The lists were compiled and then rated on the severity of the
      violation. RESULTS: From 14 usability heuristics considered in this evaluation of
      the Infusion Pump, there were 231 violations. Two heuristics, "Consistency" and
      "Language", were found to have the most violations. The one with fewest
      violations was "Document". While some heuristic evaluation categories had more
      violations than others, the most severe ones were not confined to one type. The
      Primary interface location (e.g., where loading the pump, changing doses, and
      confirming drug settings takes place) had the most occurrences of heuristic
      violations. CONCLUSION: We believe that the Heuristic Evaluation methodology
      provides a simple and cost-effective approach to discovering medical device
      deficiencies that affect a patient's general well being. While this methodology
      provides information for the infusion pump designs of the future, it also
      identifies important insights concerning equipment that is currently in use in
      critical care environments.

PMID- 15491929
TI  - The think aloud method: a guide to user interface design.
AB  - OBJECTIVES: Clinical use of computer systems has been hampered by their poorly
      designed user interfaces. The objective of this study was to design a user
      interface for a pediatric oncologists' computerized patient record with great
      consideration of their working behavior and of human computer interfacing
      principles so as to contribute to oncologists' efficiency and satisfaction in
      interaction with the system. METHODS: The think aloud method was used in
      combination with video recording to get a deep understanding of the way in which
      four pediatric oncologists searched through the paper-based patient record in
      preparing a patient visit. Protocol and video analyses was used to develop a
      cognitive task model reflecting pediatric oncologists' task behavior. This model
      was input for a prototype user interface, which was subsequently evaluated by
      eight other pediatric oncologists. RESULTS: The resulting computerized medical
      record system proved to meet pediatric oncologists' information needs and task
      behavior patterns. The design of the user interface minimized pediatric
      oncologists' work load and was highly efficient in supporting the pediatric
      oncologists in preparing their patient visits. The pediatric oncologists were
      very much satisfied with the computer system. CONCLUSIONS: It is argued that
      early involvement of cognitive engineering methods in the system design process
      may be of great help in designing systems that fully support health care
      professionals' work practices. The think aloud method, if applied under
      prescribed conditions, is a valuable information source of human task-behavior
      and as such a useful technique for requirements analysis in designing clinical
      computer systems.

PMID- 15491930
TI  - A survey about the usefulness of computerized systems to support illness
      management in clinical practice.
AB  - PURPOSE: This survey among an interdisciplinary group of clinicians was conducted
      to obtain their opinions about the usefulness of decision support systems (DSS)
      for evidence- and patient preference-based illness management, factors important
      to their implementation, and criteria for evaluating their effectiveness.
      METHODS: A questionnaire was sent by mail or electronically to a convenience
      sample of 184 nurses, physicians and other health care professionals. RESULTS:
      The DSS ability to provide information about potential benefits and harms of
      intervention options and reports on patient outcomes of symptom relief,
      functional status and preference achievement was considered most useful among DSS
      features. Nurses rated the usefulness of the DSS higher than physicians did. Ease
      of use, no increase in workload, and timely, precise information were rated as
      the most important factors for successful implementation. The most frequently
      selected patient, care process/provider and system outcomes rated as indicators
      for DSS effectiveness were: patient satisfaction, health-related quality of life,
      symptom relief, functional status, and alignment of patient preferences with
      realistic expectations; congruence between patient preferences and patient care;
      clinician time use; quality of patient documentation and cost-effectiveness.
      CONCLUSION: This survey provided crucial information to successfully develop DSS
      for evidence- and patient preference-based illness management that are perceived
      helpful by their potential users.

PMID- 15491931
TI  - An international course on strategic information management for medical
      informatics students: international perspectives and evaluation.
AB  - All over the world, countries more and more take part in the international
      society and economy. To meet the stringent requirements of this globalization
      asks for internationally oriented and well-educated graduates. A major challenge
      of academia thus lies in qualifying graduates for international positions in this
      new world. A crucial element in the training and education of tomorrow's medical
      informatics specialists is exposure to health care systems across national
      borders. In this contribution, we report on the international aspects of and
      experiences with an inter-university course for medical informatics students on
      hospital information systems, in particular on their strategic information
      management. From 2001 onwards, this course was offered jointly for students of
      the University of Amsterdam, the University of Heidelberg/University of Applied
      Sciences Heilbronn and the University of Health Informatics and Technology, Tyrol
      (UMIT). Based on our experiences, future establishment of international courses
      in the medical and health informatics field is recommended.

PMID- 15491933
TI  - Cherchez la femme, cherchez la femme: a paradoxical response to trauma.
AB  - This personal narrative is the author's account of early childhood trauma and its
      lingering effects experienced as a paradoxical response. What is later
      acknowledged (in the paper) as dissociation manifests itself throughout
      adolescence and adulthood as a fierce desire for attachment that permits no sense
      of relationship, "a many-times-distorted derivative of the unconscious libidinal
      wish-fulfillment, an ingeniously chosen piece of ambiguity with two meanings in
      complete mutual contradiction" (Freud 1917). This paper raises the following
      questions: How is trauma internalized? How does the internalization of a
      traumatic event impact one's capacity for relationship, and one's ability to
      distinguish between and derive pleasure from real versus fantasy relationships?
      If women are intrinsically more relational than men, and sexual trauma can
      distort one's sense of attachment, what is the impact on a woman's growth and
      sexuality? How does a victim of such a trauma and the therapeutic relationship
      address and overcome the pain and damage caused by this kind of experience?

PMID- 15491934
TI  - The legacy of child sexual abuse.

PMID- 15491935
TI  - Reality as an inkblot: looking at the trauma literature.

PMID- 15491936
TI  - Resilience in the face of psychological trauma.

PMID- 15491937
TI  - Stuck in the past.

PMID- 15491938
TI  - Commentary on a first-person account of sexual abuse: from experience to theory
      and treatment.

PMID- 15491939
TI  - The paradox of "detachment disorders": binding-disruptions of dissociative
      process.
AB  - This case is discussed in the contexts of affect theory, attachment theory, and
      dissociative experience. Dissociative adaptations to living that become
      entrenched resistances during psychotherapeutic inquiry give way to a scrupulous
      attention to the characteristics of dissociative experiencing. Somatosensory free
      association and appreciation of experiential aspects of depersonalization,
      derealization, and dissociative amnesia open new areas of negotiation between
      patient and therapist. Paradigms from infant attachment and adult attachment
      research parsimoniously explicate psychodynamic formulations. "Conflicted
      interest" and "conflicted disinterest" are proposed to flesh out appreciation of
      the child's inner experience during Type A and Type C attachment experiences. The
      Type D attachment style is consistent with a dissociative phenotype. The concept
      of "isolated subjectivity" can help explain the extent to which individuals both
      know and don't know about their experience, in the same moment, and without
      conscious conflict or anxiety.

PMID- 15491940
TI  - Dissociation of the "bad" parent, preservation of the "good" parent.

PMID- 15491941
TI  - A search for meaning.

PMID- 15491942
TI  - Mental health effects of adolescent trauma exposure in a female college sample:
      exploring differential outcomes based on experiences of unique trauma types and
      dimensions.
AB  - Most studies on the psychological impact of trauma exposure focus on the response
      to a single type of trauma, with little or no attention paid to the contribution
      of prior traumatic experiences. The goal of this study was to disentangle some of
      the confounding effects of multiple trauma exposures by exploring the unique
      contribution to mental health outcomes made by specific types and dimensions of
      trauma. This report compares the psychological outcomes of college women who
      experienced different types of trauma during adolescence, including traumatic
      bereavement, sexual assault, and physical assault. Young women who had
      experienced a single event of one of these types were compared with peers who had
      experienced multiple single events, ongoing sexual and/or physical abuse, as well
      as those who had experienced no trauma. Results, based on structured clinical
      interviews, and self-report measures showed that there were some significant
      differences in mental health outcomes based on trauma type. However, trauma
      exposure versus no exposure and the cumulative effects of exposure versus one
      time experiences played the key roles in differentiating the groups.

PMID- 15491943
TI  - Coping with trauma: narrative and cognitive perspectives.
AB  - The immediate period following a traumatic event is a crucial time in the
      survivors' process of recovery. During this time, a narrative of the trauma is
      generated and constructed, alongside a process of cognitive processing of the
      traumatic events. In the first part of the article we present the outlines of the
      narrative and cognitive attitudes to trauma; the second part will illustrate the
      developmental process through which the trauma narrative is shaped, in the
      stories of five survivors of a terror attack. We suggest that by analyzing three
      main components of the trauma narrative (coherence, finding meaning and self
      evaluation), together with the equivalent cognitive attitudes, it is possible to
      evaluate the process of recovery, identify foci of difficulties in this process
      and pinpoint possible therapeutic interventions in the early stages after the
      trauma.

PMID- 15491944
TI  - Follow-up after inpatient psychiatric hospitalization with partial control of the
      system responsiveness variable.
AB  - One of the most significant predictors of prompt rehospitalization following
      psychiatric hospital discharge is missing follow-up out-patient appointments.
      Previous studies have suggested that system responsiveness accounted for much of
      the variance in predicting compliance with aftercare. Collaborations established
      at our institution allowed us to partially control this variable, opening the way
      to explore other obstacles to aftercare. All severely mentally ill subjects
      discharged from our hospital are provided follow-up appointments within two
      weeks. We retrospectively evaluated compliance with aftercare appointment and
      investigated factors that were associated with compliance. Eighty-one subjects
      were evaluated. Twenty-seven (33.8 %) did not attend their first follow-up
      appointment. Subjects with a primary substance-related syndrome were the most
      likely to miss their appointment (83.3%, chi 2 = 17.02, p = .0045), as were
      uninsured patients (51.6%, chi 2 = 8.79, p = .003). There was a trend for
      individuals not previously involved with their aftercare providers to miss their
      appointment (48.9%, chi 2 = 3.35, p = .067). Despite partial control of the
      system responsiveness variable, compliance with aftercare was suboptimal. This
      was due to a combination of client vulnerability variables and uncontrollable
      system responsiveness factors.

PMID- 15491945
TI  - Countertransference revisited.
AB  - A female patient of mine recounts her week. I listen with interest, waiting for
      her to arrive at particular conclusions. She has suffered a great deal and still
      does, but prefers not to dwell on it. My interest turns into patience as she
      continues to talk but circumvents her discontent. She is adroit at avoidance, but
      easily offended when I point such things out. "I'd better wait" I think. I grow
      more aware that I must encourage her digressions. I feel frustrated. Getting
      further and further away, she skirts the issue with supple grace, then strays off
      into tangentiality. I forget her point and lose my focus, then get down on
      myself. The opportunity is soon gone. I glance at the clock as her monologue
      drones on into banality. I grow more uninterested and distant. There is a subtle
      irritation to her voice; a whiney indecisive ring begins to pervade my
      consciousness. I home in on her mouth with aversion, watching apprehensively as
      this disgusting hole flaps tirelessly but says nothing. It looks carnivorous,
      voracious. Now she is unattractive, something I have noticed before. I forget who
      my next patient is. I think about the meal I will prepare for my wife this
      evening, then glance at the time once more. Then I am struck: Why am I looking at
      the clock? So soon? The session has just begun. I catch myself. What is going on
      in me, between us? I am detached, but why? Is she too feeling unattuned,
      disconnected? I am failing my patient. What is her experience of me? I
      lamentingly confess that I do not feel I have been listening to her, and wonder
      what has gone wrong between us. I ask her if she has noticed. We talk about our
      feelings, our impact on one another, why we had lost our sense of connection,
      what it means to us. I instantly feel more involved, rejuvenated, and she
      continues, this time with me present. Her mouth is no longer odious, but sincere
      and articulate. She is attractive and tender; I suddenly feel empathy and warmth
      toward her. We are now very close. I am moved. Time flies, the session is soon
      over; we do not want it to end.

PMID- 15491946
TI  - "To never wholly die," to never fully live: death and rebirth in the emergence of
      self in the therapeutic process.

PMID- 15491947
TI  - Transforming dualism and the metaphor of terror part II: from genocidal to
      dialogic mentality: an intergenerational struggle.

PMID- 15491948
TI  - Charles Rycroft and ablation.

PMID- 15491951
TI  - Sex workers in Vietnam: how many, how risky?
AB  - Because of concerns for HIV risks and need to plan effective programs, we
      assessed the number and risks of sex workers in Nha Trang City, Vietnam. Sex
      workers were contacted in streets, beaches, bars, and restaurants, and a capture
      recapture method was used to estimate their number. An estimated 444 women worked
      on the streets and beach ("direct" sex workers) and 486 worked in bars and
      restaurants or other facilities ("indirect" sex workers). Direct and indirect sex
      workers engaged in sex work primarily to support their families. Direct sex
      workers were older and were more at risk for HIV risk than were indirect sex
      workers. Direct sex workers had more clients, were less likely to report always
      using condoms (67% vs. 81%), more likely to report a prior sexually transmitted
      infection (19% vs. 16%), and more likely to have clients who inject drugs (16%
      vs. 13%). This assessment has implications for planning programs to reduce sex
      work and its risks in Vietnam and potentially other countries.

PMID- 15491952
TI  - The Sonagachi Project: a sustainable community intervention program.
AB  - High rates of HIV infection among sex workers in India indicate the importance of
      understanding the process of establishing a sustainable community intervention
      program. The Sonagachi Project, based in Calcutta, India, has been associated
      with lower HIV rates among sex workers as compared to other urban centers in
      India. The program defined HIV as an occupational health problem and included
      multifaceted, multilevel interventions addressing community (having a high-status
      advocate; addressing environmental barriers and resources), group (changing
      social relationships), and individual factors (improving skills and competencies
      related to HIV prevention and treatment). The Sonagachi Project's core concepts
      and strategies evolved as community needs were expressed and defined. In
      particular, the program was not initially conceptualized as a community
      empowerment project but emerged over time, allowing for project sustainability.
      Project components appear to be replicable across settings within India and
      worldwide.

PMID- 15491953
TI  - Infant HIV infection: acceptability of preventive strategies in central Tanzania.
AB  - Safe, cost-effective interventions are being developed to reduce HIV transmission
      to children, suitable for lower income countries such as Tanzania. The
      interventions include Nevirapine treatment, replacement feeding, exclusive breast
      feeding and heat-treating breast milk. This article reports on research to
      explore factors, which may influence the acceptability of these interventions.
      Data collection methods used were qualitative in-depth interviews with 12 health
      workers and focus group discussions with five community groups. Findings are
      presented with reference to the theory of diffusion of innovation, which seeks to
      explain how new ideas and products are disseminated through a community.
      Respondents describe the factors that may help and hinder this process. They
      propose ways to maximize this diffusion, such as integrating HIV and antenatal
      services, encouraging male participation, community-wide education, offering free
      HIV testing, and training health workers as change agents.

PMID- 15491954
TI  - Mapping the roots of HIV/AIDS complacency: implications for program and policy
      development.

PMID- 15491955
TI  - HIV testing and awareness of care-related services among a group of HIV-positive
      Asian Americans and Pacific Islanders in the United States: findings from a
      supplemental HIV/AIDS surveillance project.
AB  - Compared with other racial/ethnic groups in the United States, Asian Americans
      and Pacific Islanders (AAPIs) are more likely to be at an advanced stage of AIDS
      disease and have opportunistic infections at the time of diagnosis. However, it
      is not clear how these two findings are related to issues such as HIV testing and
      access to HIV care-related services. We examined HIV testing and awareness of
      care-related services among a group of HIV-positive AAPIs in the United States.
      Data are from a multisite supplemental surveillance project, 1990-1999. Compared
      with Whites, a higher percentage of AAPIs cited "illness" as the main reason for
      HIV testing and had their tests done as a hospital inpatients--although these
      differences were not statistically significant. A significantly lower percentage
      of AAPIs than Whites were aware of their current CD4 count; AAPIs also had
      significantly lower awareness about a number of care-related services. Among
      AAPIs, educational level was positively associated with awareness of these
      services. Efforts are needed to promote service availability among HIV-positive
      AAPIs.

PMID- 15491956
TI  - Beliefs about HIV non-infection and risky sexual behavior among MSM.
AB  - As part of a larger investigation examining genetic immunity to HIV, we undertook
      a cross-sectional investigation of 97 HIV-seronegative men who have sex with men
      (MSM). Our aim was to better understand the factors to which these men attributed
      their HIV serostatus and to relate these attributions to sexual risk taking.
      Three beliefs were related to sexual risk taking with HIV-negative/status unknown
      casual partners: (a) medication treatment advances, (b) the low probability
      related to HIV transmission, and (c) a healthy immune system, capable of
      resisting infection. A multivariate regression model suggested that use of
      recreational drugs, in combination with the belief that treatment advances reduce
      the risk of HIV seroconversion, in part, may explain the frequency with which
      individuals engage in unprotected anal receptive intercourse. Our findings
      suggest that MSM who intentionally engage in unprotected anal sex may be
      influenced by perceptions that medical advances have mitigated the threat of HIV
      and corroborate previous studies depicting an intimate relationship between
      illicit drug use and sexual risk taking.

PMID- 15491957
TI  - Positive and negative consequences of HIV disclosure among seropositive injection
      drug users.
AB  - This study examines HIV status disclosure in an ethnically diverse sample of HIV
      seropositive injection drug users (IDUs) from New York City and San Francisco.
      Qualitative interviews were conducted with 158 participants. Analyses revealed a
      number of negative and positive consequences of disclosing serostatus to sexual
      partners. Negative consequences included stigma, rejection by sexual partners and
      others, loss of intimacy, and threats to personal well-being. Positive rewards
      resulting from disclosure included increased social support and intimacy with
      partners, reaffirmation of one's sense of self, and the opportunity to share
      personal experiences and feelings with sexual partners. The role of
      responsibility in impacting disclosure and nondisclosure revealed varied patterns
      in terms of how this construct impacts disclosure and resulting behaviors with
      sexual partners. Some participants used particular strategies, such as getting
      involved in seroconcordant relationships or minimizing intimacy in relationships,
      in order to combat potential negative outcomes of disclosure. For others,
      positive rewards were viewed as important enough to risk negative consequences.
      Interventions for HIV-positive IDUs are discussed.

PMID- 15491958
TI  - A comparison of Web- with paper-based surveys of gay and bisexual men who
      vacationed in a gay resort community.
AB  - Internet Web page survey responses were compared with those collected using
      traditional paper-and-pencil strategies to assess relative inclusion of a
      geographically dispersed population and comparativeness in responses. Three
      hundred and seven gay or bisexual men who had vacationed in a particular gay
      community completed Web-based and 244 paper-and-pencil questionnaires. Each
      questionnaire contained the same wording and question order. More Internet
      respondents than paper reported bisexual identity, nonmetropolitan residence,
      greater numbers of nonmain male partners for unprotected anal intercourse, and
      alcohol use than did paper-and-pencil respondents. Few other differences were
      identified. Assessing the reach of survey distribution can add to our knowledge
      base of surveys fielded using the Internet. Similarly, examining the potential
      biases in modes of administering convenience surveys can assist researchers to
      select the survey data collection method most appropriate to their research goals
      and design studies to assess the effect of the methods that are used.

PMID- 15491961
TI  - Warm red blood cell autoantibodies and the direct antiglobulin test revisited.

PMID- 15491962
TI  - The importance of tumor angiogenesis: the evidence continues to grow.

PMID- 15491963
TI  - Warm reactive autoantibodies: clinical and serologic correlations.
AB  - Warm reactive autoantibodies are encountered relatively frequently in tertiary
      care hospitals. We studied 100 consecutive patients with warm autoantibodies to
      correlate their clinical and serologic features. Study patients (56 male, 44
      female) had various diagnoses and a mean age of 53.5 years (range, 3-90 years).
      Autoimmune hemolysis was documented in 29 patients; 20 patients (69%) in this
      subset had diseases classically associated with warm autoimmune hemolytic anemia
      (hematologic and autoimmune disorders). All study patients demonstrated IgG on
      their RBCs (direct antiglobulin test [DAT] reactivity range, microscopic to 4+);
      49 also demonstrated C3 (reactivity range, microscopic to 3+). The DAT for IgG
      was 2+ or more in 25 (86%) of 29 patients with hemolysis; the DAT for IgG was 1+
      or less in 45 (63%) of 71 patients without hemolysis. In patients with hemolysis,
      21 (72%) of 29 had a DAT reactive for C3. These findings may be useful in
      determining the clinical significance of warm autoantibodies and the extent to
      which patients should be followed up for hemolysis.

PMID- 15491964
TI  - Potential laboratory misdiagnosis of hemophilia and von Willebrand disorder owing
      to cold activation of blood samples for testing.
AB  - To assess the potential for misdiagnosis of von Willebrand disorder (vWD) and
      hemophilia A while following current National Committee for Clinical Laboratory
      Standards (NCCLS) guidelines and consequent to a poorly recognized cold
      activation phenomenon, we processed 39 normal citrate-anticoagulated samples by
      standard procedures (reference) or stored at low (approximately 4 degrees C) or
      ambient (approximately 22 degrees C) temperature for 3.5 hours before
      centrifugation and processing. Samples were tested in parallel for several
      hemostasis factors, including von Willebrand factor (vWF). Similar results were
      obtained for all samples for factors II, V, VII, IX, X, XI, and XII. For factor
      VIII (FVIII) and vWF, only samples stored at ambient temperature had results
      comparable to reference sample results. In most cases, low temperature storage
      led to much lower results. Taking the lower reference limit as 50%, most would
      have been defined as "abnormal," and a misdiagnosis of vWD or hemophilia A could
      easily arise. ABO classification and age were associated with FVIII and vWF
      levels, but neither was associated conclusively with relative loss of plasma
      FVIII coagulant and vWF caused by the cold-activation phenomenon. We advise
      laboratories following current NCCLS guidelines not to store or transport whole
      blood samples for FVIII and vWF testing at 2 degrees C to 4 degrees C because of
      the risk of misdiagnosing vWD or hemophilia A. Storage and transport at ambient
      temperature seem acceptable and provide results comparable to freshly centrifuged
      samples.

PMID- 15491965
TI  - Hypercholesterolemia impairs angiogenesis in patients with breast carcinoma and,
      therefore, lowers the risk of metastases.
AB  - Our aim was to study the effect of hypercholesterolemia on angiogenesis induced
      by breast carcinoma. Of 51 patients with invasive ductal carcinoma, 28 had
      hypercholesterolemia and 23 had normocholesterolemia. The intratumoral
      microvessel density (MVD) was evaluated by using anti-CD31 antibody. The
      expression of basic fibroblast growth factor (bFGF) and vascular endothelial
      growth factor (VEGF) on endothelial and tumor cells was examined and graded
      semiquantitatively. Patients with normocholesterolemia had a higher MVD (76.4 +/-
      8.2) than those with hypercholesterolemia (54.6 +/- 5.1) (P < .01). The risks of
      recurrence and distant metastasis were higher in patients with
      normocholesterolemia than in patients with hypercholesterolemia (P < .01).
      Patients with hypercholesterolemia showed lower expression of endothelial VEGF
      and bFGF than patients with normocholesterolemia (P < .05 and P < .01,
      respectively). In addition, tumoral bFGF and VEGF expression showed negative
      correlation with the presence of hypercholesterolemia (P < .01). We suggest that
      hypercholesterolemia impairs angiogenesis by suppressing endothelial and tumoral
      bFGF and VEGF expression and, therefore, lowers the risk of metastases in cases
      of invasive breast carcinoma.

PMID- 15491966
TI  - Rapid intraoperative parathyroid hormone testing with surgical pathology
      correlations: the "chemical frozen section".
AB  - The classic surgical approach to patients undergoing parathyroidectomy for
      primary or secondary hyperparathyroidism has experienced a dramatic shift owing
      to preoperative localization of the affected glands and/or the use of rapid
      intraoperative parathyroid hormone (RI-PTH) assays, allowing for minimally
      invasive surgical excisions. Institutional experience with 141 patients who
      underwent parathyroidectomy aided by the use of RI-PTH is reviewed. The
      orientation provided by the intraoperative assay is essential in guiding the
      surgeon in these minimally invasive procedures, it helps reveal the cases of
      primary hyperparathyroidism with involvement of more than 1 gland, and it
      replaces the need for performing frozen sections, except for cases of secondary
      hyperparathyroidism.

PMID- 15491967
TI  - Lobulocentricity of breast hypersecretory hyperplasia with cytologic atypia:
      infrequent association with carcinoma in situ.
AB  - Intracytoplasmic and extracytoplasmic features of secretion, similar to
      lactational changes, occasionally are seen in the nonparous human breast, usually
      are lobulocentric, and often have aberrant cytologic and nuclear changes. In
      these "hypersecretory hyperplasias" (HHs; 38 women) there is bubbly cytoplasm
      with irregular apical cytoplasmic and/or nuclear protrusions. In a review of 138
      HH cases the following additional associated changes were found: nuclear atypia
      (HHA, 22 women), atypical ductal hyperplasia (ADH-HH, 24 women), and ductal
      carcinoma in situ (DCIS-HH, 54 women). A diagnosis of DCIS-HH requires
      involvement of true duct(s) and of several contiguous lobular units, emphasizing
      the importance of extent and overall size and similar cytology and histologic
      arrangement of intercellular spaces indicating a homogeneous cell population.
      Cases of HH regularly are characterized as having adjacent and nearby lobular
      units with quite diverse cytologic patterns. The major impact of this study is to
      recognize that HHA may be regarded as having uncertain significance when found
      alone in the usual presentation in a single unit, but that formally defined ADH
      and/or DCIS may be locally present.

PMID- 15491968
TI  - Hepatocyte paraffin 1 expression in human normal and neoplastic tissues: tissue
      microarray analysis on 3,940 tissue samples.
AB  - Hepatocyte paraffin 1 (Hep Par 1) is a monoclonal antibody developed from hepatic
      tissue from a failed liver allograft. Several studies have shown that Hep Par 1
      is a useful marker to differentiate hepatocellular carcinoma (HCC) from other
      types of adenocarcinoma metastatic to the liver. The aim of our study was the
      systematic investigation of the epidemiology of Hep Par 1 expression in 3,940
      tissue samples using the tissue microarray technique. Strong Hep Par 1 expression
      was found most frequently in 35 (73%) of 48 HCCs. In nonhepatic tumors, strong
      Hep Par 1 expression was detected in adenocarcinoma of the lung (2/50),
      gallbladder (3/31), pancreas (2/48), stomach (3/74), small intestine (1/11),
      adenoma of the colon with high-grade dysplasia (1/49), adrenal gland carcinoma
      (1/6), paraganglioma (1/9), and malignant melanoma (2/48). Our data suggest that
      Hep Par 1 is a highly specific marker for HCC, although several nonhepatic tumors
      occasionally can show some Hep Par 1 positivity.

PMID- 15491969
TI  - Refined morphologic criteria for tubular carcinoma to retain its favorable
      outcome status in contemporary breast carcinoma patients.
AB  - We studied outcomes of 147 patients with stage I/II grade 1 (32 pure tubular, 115
      ductal) carcinoma treated with breast-conserving therapy to evaluate the
      prognostic usefulness of standard and recently proposed revised criteria for
      tubular (tubularity percentage [proportion of neoplastic cells adjacent to open
      lumens], nuclear grade, and mitoses) and ductal carcinoma. Carcinomas with less
      than 70% tubularity were ductal. Carcinomas with 70% or more tubularity were
      divided into those with occasional grade 2 nuclei and mitoses and those with pure
      grade 1 nuclei and rare or no mitoses. The 10-year disease-free survival for
      patients with pure ductal vs pure tubular carcinoma was 91% vs 96% (P = .036).
      Overall survival rates were similar (85% vs 89%; P = .161). With the recently
      proposed criteria, neoplasms with less than 70% tubularity; 70% or more
      tubularity and occasional grade 2 nuclei and mitoses; and 70% or more tubularity,
      pure grade 1 nuclei, and rare mitoses had 10-year disease-free survival rates of
      88%, 93%, and 100% (P < .001) and 10-year overall survival rates of 85%, 88%, and
      94%, respectively (P < .001). Tubular carcinoma as a distinct morphologic entity
      should be restricted to neoplasms with 70% or more tubularity, pure grade 1
      nuclei, and rare mitoses. Other definitions of tubular carcinoma do not guarantee
      the excellent prognosis.

PMID- 15491970
TI  - Frequent CpG island methylation in sporadic and syndromic gastric fundic gland
      polyps.
AB  - We studied methylation of 2 tumor suppressor genes (p14, p16) and 4 MINT
      (methylated in tumor) clones (MINT1, MINT2, MINT25, MINT31) among 51 fundic gland
      polyps (FGPs) and 27 normal gastric body biopsy samples using bisulfite treatment
      of genomic DNA followed by methylation-specific polymerase chain reaction. Thirty
      two FGPs were syndromic polyps from 14 patients with familial adenomatous
      polyposis (FAP); 19 were sporadic FGPs from 15 patients without FAP.
      Significantly higher mean methylation indices were found between FGPs and normal
      gastric mucosa (P = .012). FGPs arising in a background of proton pump inhibitor
      (PPI) effect had significantly higher mean methylation indices than those that
      did not (P = .023). Perhaps because sporadic FGPs were more likely to be
      associated with PPI effect than were FAP-associated FGPs, they also demonstrated
      higher mean methylation indices than syndromic polyps (P = .024). Among FAP
      associated FGPs, there was no statistical difference in methylation indices
      between polyps that were dysplastic, indefinite for dysplasia, or nondysplastic
      (P = .87). Epigenetic alterations involving methylation of CpG islands might have
      a role in the development of some FGPs, particularly those with a PPI effect.
      They do not account for the presence or absence of a dysplastic phenotype in
      FGPs.

PMID- 15491971
TI  - Overexpression of human carcinoma-associated antigen in esophageal adenocarcinoma
      and its precursor lesions.
AB  - The expression of human carcinoma-associated antigen (HCA), a mucin-type
      glycoprotein, was assessed in 50 esophagogastrectomy specimens. Areas, each from
      different cases, of Barrett esophagus (n = 36), low-grade dysplasia (n = 38),
      high-grade dysplasia/carcinoma in situ (n = 26), and esophageal adenocarcinoma
      (EAC; n = 34) were examined by immunohistochemical stains to 2 anti-HCA
      monoclonal antibodies, G1 and HAE3. These two antibodies showed similar staining
      patterns. HCA was overexpressed significantly in EAC and high-grade
      dysplasia/carcinoma in situ compared with benign esophageal mucosa (P < .001 for
      both), Barrett esophagus (P < .001 for both), and low-grade dysplasia (P < .025
      for both). HCA overexpression did not correlate with the grade of EAC (P > .1).
      The results suggest that overexpression of HCA might help in diagnosing
      esophageal dysplasia and cancer. The correlation of HCA with the grade of
      esophageal dysplasia suggests its possible involvement in the pathogenesis of
      EAC. HCA also might provide a target for immunotherapy.

PMID- 15491972
TI  - Pathogenesis and diagnosis of human meningococcal disease using
      immunohistochemical and PCR assays.
AB  - Neisseria meningitidis remains the leading cause of fatal sepsis. Cultures may
      not be available in fulminant fatal cases. An immunohistochemical assay for N
      meningitidis was applied to formalin-fixed samples from 14 patients with
      meningococcal disease. Histopathologic findings in 12 fatal cases included
      interstitial pneumonitis, hemorrhagic adrenal glands, myocarditis, meningitis,
      and thrombi in the glomeruli and choroid plexus. Meningeal inflammation was
      observed in 6 patients. Skin biopsies of 2 surviving patients showed
      leukocytoclastic vasculitis and cellulitis. By using immunohistochemical
      analysis, meningococci and granular meningococcal antigens were observed inside
      monocytes, neutrophils, and endothelial cells or extracellularly. By using real
      time polymerase chain reaction (PCR) on formalin-fixed tissue samples,
      meningococcal serogroup determination was possible in 11 of 14 cases (8 serogroup
      C, 2 Y, and 1 B). Diagnosis and serogrouping of N meningitidis can be performed
      using immunohistochemical analysis and PCR on formalin-fixed tissue samples.
      Immunohistochemical analysis determined the distribution of meningococci and
      meningococcal antigens in tissue samples, allowing better insights into N
      meningitidis pathogenesis.

PMID- 15491973
TI  - Spleen depletion in neonatal sepsis and chorioamnionitis.
AB  - Neonatal sepsis and chorioamnionitis induce morphologic modifications and
      shrinkage of the thymus. We show fetal and neonatal morphologic modifications of
      the spleen in the same autopsy subjects as previously used to describe thymus
      shrinkage, including 10 preterm or full-term neonates who died of proven sepsis
      within 48 hours after birth and 20 fetuses spontaneously aborted because of
      extensive ascending chorioamnionitis. Control subjects included 10 fetuses from
      induced termination of pregnancy and 10 neonates who died suddenly during the
      perinatal period without evidence of chorioamnionitis. Spleen cell populations
      were studied by means of immunohistochemical analysis. Neonatal sepsis occurred
      with severe spleen depletion, involving both B and T lymphocytes (P < .001).
      Fetuses with chorioamnionitis also showed spleen cell depletion. These
      observations, to our knowledge not described before, indicate that preterm and
      term neonates show an inflammatory reaction similar to that of adult patients and
      that severe chorioamnionitis is associated with a nonspecific inflammatory
      response comparable to that of sepsis.

PMID- 15491974
TI  - Flow cytometric DNA ploidy analysis of peripheral blood from patients with sezary
      syndrome: detection of aneuploid neoplastic T cells in the blood is associated
      with large cell transformation in tissue.
AB  - We reviewed and screened 219 cutaneous T-cell lymphoma (CTCL) cases for Sezary
      syndrome (SS); 63 met the criteria for SS. Of these, 17 (27%) demonstrated
      circulating aneuploid cells and 46 (73%) showed only euploid cells in blood
      samples. Of 17 aneuploid cases, DNA ploidy study was essential for initial blood
      based diagnosis of SS in 4 (24%) and important in monitoring minimal residual
      disease after treatment in 9 (53%) in which neoplastic T cells showed otherwise
      unremarkable or nonspecific flow cytometric immunophenotypic findings. Tissue
      biopsy slides (predominantly skin and lymph node) at the time of DNA ploidy
      studies were available for 47 of 63 cases. Of 14 cases with circulating aneuploid
      cells, 11 (79%) showed large cell transformation (LCT; 6 [43%]) or markedly
      increased large cells (ILC; 5 [36%]) in tissue, whereas only 10 (30%) of 33
      euploid cases showed LCT (4 [12%]) or ILC (6 [18%]) (P < .01). There was no
      significant difference in blood tumor burden, immunophenotype, or proliferation
      index between euploid and aneuploid groups or histologic high- and low-grade
      groups. DNA ploidy study by flow cytometry is important for blood-based diagnosis
      of SS and detection of minimal residual disease in aneuploid SS after treatment.
      Detection of aneuploid neoplastic T cells in peripheral blood samples of patients
      with CTCL is associated with LCT in skin, lymph node, or other tissues.

PMID- 15491975
TI  - Post-PCR multiplex fluorescent ligation detection assay and flow cytometry for
      rapid detection of gene-specific translocations in leukemia.
AB  - We describe a novel method to detect specific polymerase chain reaction (PCR)
      target amplicons, involving thermostable ligation of fluorescent and biotinylated
      oligonucleotides, microparticle bead capture of the ligated products, and flow
      cytometric analysis. This approach, termed fluorescent ligation detection
      reaction (f-LDR) is more rapid and cost-effective than oligoprobe Southern blot
      hybridization (SBH). A standard f-LDR protocol was developed to detect the
      leukemia-associated chimeric transcripts bcr-abl and promyelocytic leukemia
      retinoic acid receptor a (PML-RARalpha) in 2 multiplex and multicolor assays. The
      f-LDR platform was 100% specific and demonstrated comparable or better
      sensitivity than standard oligoprobe SBH. The usefulness of f-LDR was evaluated
      in 94 posttherapy samples from 13 patients with acute promyelocytic leukemia with
      the PML-RARalpha gene fusion. The f-LDR method was highly concordant (93%) with
      oligoprobe SBH; essentially all discrepancies were noted to be due to the
      enhanced sensitivity of f-LDR. We conclude that f-LDR is a highly specific and
      sensitive post-PCR method with wide potential application.

PMID- 15491976
TI  - CD163: a specific marker of macrophages in paraffin-embedded tissue samples.
AB  - Paraffin-section immunohistochemical analysis was performed using a monoclonal
      antibody against CD163 to evaluate the antibody's usefulness in identifying cells
      of monocyte/macrophage lineage in normal and neoplastic conditions. Normal human
      tissue samples and samples from 211 hematopoietic disorders and 115
      nonhematopoietic neoplasms were examined. The distribution of KP1 and PG-M1,
      monoclonal antibodies to the macrophage-associated CD68 antigen, also were
      evaluated for comparison. CD163 immunoreactivity was observed in resident
      macrophages of all normal tissue samples except splenic white pulp macrophages
      and germinal center tingible body macrophages. Among hematopoietic disorders and
      nonhematopoietic neoplasms, CD163 expression was restricted largely to cases of
      chronic myelomonocytic leukemia, histiocytic sarcoma, sinus histiocytosis with
      massive lymphadenopathy, and littoral cell angioma. Acute myeloid leukemias
      (AMLs) with monocytic differentiation were CD163- with the exception of 1 case of
      acute monoblastic leukemia. Most myeloid sarcomas also were CD163-. Compared with
      the CD68 antibodies, CD163 demonstrated greater specificity as a marker of
      disorders of monocyte/macrophage origin. However, immunohistochemical evaluation
      of CD163 expression does not seem to be a sensitive means of determining
      monocytic differentiation in AMLs in paraffin sections or establishing a
      diagnosis of myeloid sarcoma.

PMID- 15491977
TI  - Sigma ESR: an erythrocyte sedimentation rate adjusted for the hematocrit and
      hemoglobin concentration.
AB  - The aim of the study was to simplify the first Sigma erythrocyte sedimentation
      rate (ESR) method (manual hematocrit adjustment to 0.35, sum of 4 sedimentation
      levels) and to confirm its clinical relevance. The erythrocyte sedimentation rate
      of undiluted blood samples from 576 patients was measured simultaneously with and
      without manual hematocrit adjustment to 0.35 to identify an approximate
      expression of the area under the curve and a formula for calculating the Sigma
      ESR. The Sigma ESR formula was based on the sum of 2 unadjusted sedimentation
      levels, at 30 and 60 minutes, together with the hematocrit value and the
      hemoglobin concentration. Sigma ESR values in 274 healthy subjects showed a
      gaussian distribution, no difference between men and women, and no significant
      increase with age. In recent-onset arthritis or disk-related lumbosciatic
      syndrome, Sigma ESR seemed to be a more reliable marker of inflammation than the
      Westergren ESR and C-reactive protein. We also obtained data clarifying the
      controversial relationship of ESR with lipid levels and arterial hypertension.

PMID- 15491978
TI  - Protein kinase C activation promotes the internalization of the human cationic
      amino acid transporter hCAT-1. A new regulatory mechanism for hCAT-1 activity.
AB  - The human cationic amino acid transporter hCAT-1 is almost ubiquitously expressed
      and probably the most important entity for supplying cells with extracellular
      arginine, lysine, and ornithine. We have previously shown that hCAT-1-mediated
      transport is decreased after protein kinase C (PKC) activation by phorbol 12
      myristate 13-acetate (PMA) (Graf, P., Forstermann, U., and Closs, E. I. (2001)
      Br. J. Pharmacol. 132, 1193-1200). In the present study, we examined the
      mechanism of this down-regulation. In both Xenopus laevis oocytes and U373MG
      glioblastoma cells, PMA treatment promoted the internalization of hCAT-1 (fused
      to the enhanced green fluorescence protein (EGFP)) as visualized by fluorescence
      microscopy. Biotinylation of cell surface proteins and subsequent Western blot
      analyses confirmed that the cell surface expression of hCAT-1.EGFP was
      significantly reduced upon PMA treatment. Pretreatment with the PKC inhibitor
      bisindolylmaleimide I prevented the reduction by PMA of both hCAT-1.EGFP-induced
      arginine transport and the internalization of the transporter. Similar results
      were obtained with hCAT-1 expressed endogenously in DLD-1 colon carcinoma cells.
      Inhibition of protein synthesis did not augment the PMA effect. In addition, the
      PMA effect was reverted in washout experiments without changing the hCAT-1
      protein expression, suggesting that the PMA effect is reversible in these cells.
      PKC did not phosphorylate hCAT-1 directly as evidenced by in vivo phosphorylation
      experiments and mutational analysis, indicating an indirect action of PKC on hCAT
      1.

PMID- 15491979
TI  - The longer term outcome of children born to mothers with epilepsy.
AB  - OBJECTIVES: To determine the prevalence of cognitive delay and possible
      associated dysmorphic features in children exposed to antiepileptic drugs (AEDs)
      in utero. DESIGN: Retrospective study of children born to mothers with epilepsy.
      SETTING: Regional epilepsy clinics in Liverpool and Manchester, UK. PARTICIPANTS:
      Children aged between 6 months and 16 years born to mothers with epilepsy. MAIN
      OUTCOME MEASURES: Structured interviews, hospital records, clinical examination,
      and psychometric tests (Wechsler) were used to assess exposure and intelligence
      quotient (IQ). Blinded assessment of photographs was used to score children with
      characteristic dysmorphic features. RESULTS: A total of 249 children aged 6 and
      over were studied: 41 were exposed to sodium valproate, 52 to carbamazepine, 21
      to phenytoin, 49 to polytherapy, and 80 were unexposed. Mean verbal IQ was
      significantly lower in the valproate group compared to unexposed and other
      monotherapy groups. Multiple regression analysis showed that both valproate
      exposure and frequent tonic-clonic seizures in pregnancy were significantly
      associated with a lower verbal IQ despite adjusting for other confounding
      factors. There was a significant negative correlation between dysmorphic features
      and verbal IQ in children exposed to valproate. CONCLUSIONS: This study
      identifies valproate as a drug carrying potential risks for developmental delay
      and cognitive impairment and is the first to suggest that frequent tonic-clonic
      seizures have a similar effect. Our results need to be interpreted with caution
      given their retrospective nature. Women with epilepsy need careful counselling
      about individual risk benefit of AED treatment before pregnancy.

PMID- 15491980
TI  - Quality of life in children surviving cancer: a personality and multi-informant
      perspective.
AB  - OBJECTIVE: To describe quality of life (QoL) of children surviving cancer in
      relation to their personality, using self- and maternal reports and examining
      differences with healthy referents. METHOD: Sixty-seven children who survived
      childhood cancer were compared with eighty-one healthy children on QoL and
      personality characteristics. RESULTS: Children who survived cancer reported
      higher QoL than healthy children, whereas there were no differences for
      personality. Two main effects emerged for informant with children rating
      themselves as less neurotic and more conscientious than their mothers. The
      correspondence between mothers and children was substantially higher for
      survivors for QoL and personality ratings. QoL and trait measures share
      substantial variance, and personality traits significantly predict QoL. Parental
      personality ratings explained child QoL beyond children's personality ratings.
      CONCLUSIONS: Personality traits contribute to quality of life, indicating that
      personality significantly influences child's quality of life beyond the
      experience of a negative life event such as surviving cancer and its treatment.
      From a diagnostic perspective, parental trait ratings are informative in addition
      to children's ratings of personality to understand children's QoL.

PMID- 15491981
TI  - Coping and family functioning predict longitudinal psychological adaptation of
      siblings of childhood cancer patients.
AB  - OBJECTIVE: To assess associations of coping and family functioning with
      psychosocial adjustment in siblings of pediatric cancer patients at 1, 6, 12, and
      24 months after diagnosis. METHODS: Eighty-three siblings (ages 7-19 years)
      participated. Effects on anxiety, quality of life, behavioral-emotional problems,
      and emotional reactions to the illness were investigated. Data-analysis was
      performed with multilevel mixed modeling. RESULTS: Psychosocial functioning was
      impaired at 1 month but ameliorated over time. Adjustment problems were
      associated with high family adaptation and cohesion, older age, and female
      gender. Lower anxiety, insecurity, loneliness, and illness involvement were
      related to siblings' ability to remain optimistic. Insecurity and illness
      involvement were positively related to reliance on the medical specialist and a
      tendency to seek information about the illness. CONCLUSIONS: Siblings of
      pediatric cancer patients are most affected by the illness in the first months.
      Children at risk may be identified according to sibling age and gender and
      according to long-term family adaptation processes and sibling coping abilities.

PMID- 15491982
TI  - Anxiety and depressive symptoms and anxiety sensitivity in youngsters with
      noncardiac chest pain and benign heart murmurs.
AB  - OBJECTIVE: Chest pain in children and adolescents is rarely associated with
      cardiac disease. We sought to examine psychological symptoms in youngsters with
      medically unexplained chest pain. We hypothesized that children and adolescents
      with medically unexplained chest pain would have high rates of anxiety and
      depressive symptoms. METHODS: We assessed 65 youngsters with noncardiac chest
      pain (NCCP) and 45 comparison youngsters with benign heart murmurs using self
      report measures of anxiety and depressive symptoms and anxiety sensitivity.
      RESULTS: Compared with the asymptomatic benign-murmur group, youngsters with NCCP
      had higher levels of some anxiety symptoms and anxiety sensitivity. Differences
      on depressive symptoms were not significant. CONCLUSIONS: Though preliminary,
      results suggest that youngsters with chest pain may experience increased levels
      of some psychological symptoms. Future studies of noncardiac chest pain in
      youngsters should include larger samples and comprehensive diagnostic assessments
      as well as long-term follow-up evaluations.

PMID- 15491983
TI  - Body size stigmatization in preschool children: the role of control attributions.
AB  - OBJECTIVE: The current study assessed preschool-age children's control
      attributions for weight and the relationship of these attributions to attitudes
      and behavioral intentions toward children of different body sizes. METHODS: Forty
      two children (mean age = 5.2 years) were interviewed about the adjectives they
      attributed to figures of different sizes, their preference for size in playmates,
      and their beliefs about children's ability to control their own weight. RESULTS:
      Adjective ratings for obese figures were the most negative, with no differences
      found for thin and average figures; the heaviest figure was also chosen less
      often than other figures to be a playmate. Internal attributions of control for
      weight were related to less positive adjective ratings for the heavier figure but
      not to children's friendship selections. CONCLUSION: Results suggest that the
      relationship between body size stigmatization and control attributions are
      consistent with attribution theory for young children. Practical implications of
      these results and possible interventions are discussed.

PMID- 15491984
TI  - Brief report: Evaluation of an interactive intervention designed to reduce
      pediatric distress during radiation therapy procedures.
AB  - OBJECTIVE: To evaluate the efficacy of an interactive intervention in reducing
      distress related to radiation therapy (RT) among pediatric cancer participants as
      measured by occurrence of sedation, observed behavioral distress (OBD), and heart
      rate (HR). METHODS: Seventy-nine children receiving RT simulation were assigned
      randomly to a STARBRIGHT Hospital Pals group (i.e., interactive intervention
      group; IG) or modified control group (MCG). The interactive intervention included
      filmed modeling, exposure to an interactive Barney character, and passive
      auditory distraction. RESULTS: Children in the IG experienced significantly lower
      HR when compared with MCG participants. No differences were found in terms of
      sedation or OBD. CONCLUSIONS: The interactive intervention was effective at
      reducing RT-related distress (as measured by HR) and would be a useful tool in
      pediatric radiation oncology settings.

PMID- 15491985
TI  - Brief report: Academic attainment in children with sickle cell disease.
AB  - OBJECTIVE: To examine the impact of sickle cell disease (SCD) on academic
      attainment; the relation between academic attainment and achievement in SCD; and
      determinants of attainment in SCD. METHODS: Children with SCD and demographically
      matched peers were compared on academic attainment. Hematocrit, illness
      frequency, cognitive ability, and socioeconomic status were used to model the
      predictors of attainment problems. RESULTS: Attainment problems were more
      frequent in children with SCD (> or =31% vs. 14%). A significant number of
      children showed difficulties with only attainment or academic achievement.
      Cognitive ability was a strong predictor of both academic outcome measures.
      Illness-related school absences predicted academic attainment but not
      achievement. CONCLUSIONS: Academic attainment is affected by SCD. Tests of
      academic achievement are meaningful predictors of functional impairments for
      children with SCD; however, school outcomes are best evaluated with both
      achievement and attainment measures.

PMID- 15491986
TI  - Brief report: Development and pilot testing of a coping questionnaire for
      children and adolescents with chronic health conditions.
AB  - OBJECTIVE: The current paper describes the development, pilot testing, and item
      reduction process of a coping questionnaire for children and adolescents with
      chronic health conditions. METHODS: A pilot test with 188 children and
      adolescents was conducted in six European countries. Included in the test were
      children and adolescents (ages ranging 8-18 years) with various chronic health
      conditions-asthma, epilepsy, diabetes, arthritis, atopic dermatitis, cerebral
      palsy, or cystic fibrosis. Based on the focus groups with the children and
      adolescents and on expert consulting, items were developed and translated into
      the participants' respective languages. Data were analyzed according to
      predefined psychometric and content criteria. RESULTS: Analyses resulted in a
      selection of 29 out of 50 items for the final coping questionnaire with six
      domains: Acceptance alpha = .83, Avoidance alpha = .72, Cognitive-Palliative
      alpha = .69, Distance alpha = .70, Emotional Reaction alpha = .82, and Wishful
      Thinking alpha = .81. CONCLUSIONS: This study developed a short reliable
      international questionnaire to assess coping strategies of children and
      adolescents with chronic health conditions. Ongoing research will investigate the
      validity of this new coping questionnaire.

PMID- 15491987
TI  - Review: Accounting for prematurity in developmental assessment and the use of age
      adjusted scores.
AB  - OBJECTIVE: This review summarizes the literature to date concerning age
      adjustment in developmental assessment and illustrates relevant issues for
      clinicians and researchers in this area. METHODS: Pubmed, Medline, Premedline,
      and PsycInfo databases were used to search the following terms: assessment,
      prematurity, age adjustment, and adjusted age. Additional sources were obtained
      through the references listed in the primary articles. RESULTS: Differences in
      clinical opinions persist with regard to whether, what type, and how long age
      adjustments are to be made for premature infants. Research is inconclusive
      regarding the most appropriate method for accounting for prematurity.
      CONCLUSIONS: Previous data may no longer describe the current population of
      premature infants. Current research is needed to inform developmental assessment
      practices for this population. Meanwhile, clinicians should remain aware of the
      issues regarding whether and how to adjust for prematurity. The authors recommend
      a multifaceted approach to clinical decision making and provide suggestions for
      future research.

PMID- 15491988
TI  - Single-suture craniosynostosis: a review of neurobehavioral research and theory.
AB  - OBJECTIVE: To review research and theory regarding the neurobehavioral correlates
      and outcomes of single-suture, or isolated, craniosynostosis in children.
      METHODS: A critical review of 17 studies of the hypothesized association between
      isolated craniosynostosis and neurodevelopment. RESULTS: Isolated
      craniosynostosis is associated with a three- to fivefold increase in risk for
      cognitive deficits or learning/language disabilities. The causal basis for this
      association is unclear. No particular calvarial suture (sagittal, metopic, left
      or right unilateral coronal) has been associated with higher risk of problems.
      There is little evidence from quasi-experimental studies that cranioplastic
      surgery prevents or reduces risk of neurobehavioral impairment. CONCLUSIONS:
      Future studies would benefit from larger samples and larger control groups;
      measures of specific neuropsychological functions (in addition to global
      cognition); analyses of neuropsychological status in relation to the severity and
      cortical impact of synostosis; and an examination of interactions between
      synostosis and social/family risk factors on neurodevelopment. Routine
      neurodevelopmental screening of young children with isolated craniosynostosis is
      recommended.

PMID- 15491989
TI  - Characterization of a cardiac-specific enhancer, which directs {alpha}-cardiac
      actin gene transcription in the mouse adult heart.
AB  - Expression of the mouse alpha-cardiac actin gene in skeletal and cardiac muscle
      is regulated by enhancers lying 5' to the proximal promoter. Here we report the
      characterization of a cardiac-specific enhancer located within -2.354/-1.36 kbp
      of the gene, which is active in cardiocytes but not in C2 skeletal muscle cells.
      In vivo it directs reporter gene expression to the adult heart, where the
      proximal promoter alone is inactive. An 85-bp region within the enhancer is
      highly conserved between human and mouse and contains a central AT-rich site,
      which is essential for enhancer activity. This site binds myocyte enhancer factor
      (MEF)2 factors, principally MEF2D and MEF2A in cardiocyte nuclear extracts. These
      results are discussed in the context of MEF2 activity and of the regulation of
      the alpha-cardiac actin locus.

PMID- 15491990
TI  - Re-examination of the role of suppressor of cytokine signaling 1 (SOCS1) in the
      regulation of toll-like receptor signaling.
AB  - Suppressor of cytokine signaling 1 (SOCS1) is an obligate negative regulator of
      cytokine signaling and most importantly in vivo, signaling via the interferon
      gamma (IFN-gamma) receptor. SOCS1, via its Src homology 2 domain, binds to
      phosphotyrosine residues in its targets, reducing the amplitude of signaling from
      cytokine receptors. SOCS1 is also implicated in blocking Toll-like receptor (TLR)
      signaling in macrophages activated by TLR agonists such as lipopolysaccharide
      (LPS), thus regulating multiple steps in the activation of innate immune
      responses. To rigorously test this, we isolated macrophages from Socs1-/- mice on
      multiple genetic backgrounds. We found no evidence that SOCS1 blocked TLR
      activated pathways, endotoxin tolerance, or nitric oxide production. However,
      Socs1-/-;IFN-gamma-/- mice were extremely susceptible to LPS challenge,
      confirming previous findings. Because LPS induces IFN-beta production from
      macrophages, we tested whether SOCS1 regulates IFN-alpha/beta receptor signaling.
      We find that SOCS1 is required to inhibit IFN-alpha/beta receptor signaling in
      vitro. Furthermore, the absence of a single allele encoding TYK2, a JAK (Janus
      kinase) family member essential IFN-alpha/beta receptor signaling, rescued Socs1
      /- mice from early lethality, even in the presence of IFN-gamma. We conclude that
      previous reports linking SOCS1 to TLR signaling are most likely due to effects on
      IFN-alpha/beta receptor signaling.

PMID- 15491991
TI  - Suppressor of cytokine signaling (SOCS) proteins indirectly regulate toll-like
      receptor signaling in innate immune cells.
AB  - Suppressor of cytokine signaling (SOCS) proteins constitute a class of negative
      regulators for Janus kinase/signal transducer and activator of transcription
      (JAK/STAT) signaling pathways. These intracellular proteins are induced by
      cytokine signaling, but they can also be induced by stimulation of Toll-like
      receptors (TLR). It has even been suggested that SOCS proteins are important
      negative regulators of TLR signaling. Here we have elucidated the nature of the
      regulatory role of SOCS in TLR signaling. Induction of SOCS-3 and cytokine
      inducible Src homology 2-containing protein (CIS) by TLR stimulation was strictly
      dependent on MyD88 but showed differing needs in case of SOCS-1. However,
      induction of SOCS proteins by TLR ligands was independent of type I interferon.
      In macrophages overexpressing SOCS, we were not able to observe an inhibitory
      effect of SOCS-1, SOCS-2, SOCS-3, or CIS on prototypical TLR target genes such as
      tumor necrosis factor-alpha. However, we found that TLR-2, TLR-3, TLR-4, and TLR
      9 stimulation induced interferon-beta (IFN-beta), which is able to exert auto-
      and paracrine signaling, leading to the activation of secondary genes like IP-10.
      SOCS-1 and, to a lesser extent, SOCS-3 and CIS were able to inhibit this indirect
      signaling pathway following TLR stimulation, whereas neither MAP kinase nor NF
      kappa B signaling were affected. However, STAT-1 tyrosine phosphorylation
      following TLR triggering was severely impaired by SOCS-1 overexpression. Thus,
      our data suggest that SOCS proteins induced by TLR stimulation limit the extent
      of TLR signaling by inhibiting type I IFN signaling but not the main NF kappa B
      pathway.

PMID- 15491992
TI  - Degradation of antizyme inhibitor, an ornithine decarboxylase homologous protein,
      is ubiquitin-dependent and is inhibited by antizyme.
AB  - Ornithine decarboxylase (ODC) is the most notable example of a protein degraded
      by the 26 S proteasome without ubiquitination. Instead, ODC is targeted to
      degradation by direct binding to a polyamine-induced protein termed antizyme
      (Az). Antizyme inhibitor (AzI) is an ODC-related protein that does not retain
      enzymatic activity yet binds Az with higher affinity than ODC. We show here that
      like ODC, AzI is also a short-lived protein that undergoes proteasomal
      degradation. However, in contrast to ODC degradation, the degradation of AzI is
      ubiquitin-dependent and does not require interaction with Az. Moreover, Az
      binding actually stabilizes AzI by inhibiting its ubiquitination. Substituting
      the C terminus of AzI with that of ODC, which together with Az constitutes the
      complete degradation signal of ODC, does not subvert AzI degradation from the
      ubiquitin-dependent mode to the Az-dependent mode, suggesting dominance of the
      ubiquitination signal. Our results suggest opposing roles of Az in regulating the
      degradation of AzI and ODC.

PMID- 15491993
TI  - The conserved immunoglobulin domain controls the subcellular localization of the
      homophilic adhesion receptor protein-tyrosine phosphatase mu.
AB  - The receptor protein-tyrosine phosphatase mu (PTPmu) is a homophilic adhesion
      protein thought to regulate cell-cell adhesion in the vascular endothelium
      through dephosphorylation of cell junction proteins. In subconfluent cell
      cultures, PTPmu resides in an intracellular membrane pool; however, as culture
      density increases and cell contacts form, the phosphatase localizes to sites of
      cell-cell contact, and its expression level increases. These characteristics of
      PTPmu, which are consistent with a role in cell-cell adhesion, suggest that
      control of subcellular localization is an important mechanism to regulate the
      function of this phosphatase. To gain a better understanding of how PTPmu is
      regulated, we examined the importance of the conserved immunoglobulin domain,
      containing the homophilic binding site, in control of the localization of the
      enzyme. Deletion of the immunoglobulin domain impaired localization of PTPmu to
      the cell-cell contacts in endothelial and epithelial cells. In addition, deletion
      of the immunoglobulin domain affected the distribution of PTPmu in subconfluent
      endothelial cells when homophilic binding to another PTPmu molecule on an
      apposing cell was not possible, resulting in an accumulation of the mutant
      phosphatase at the cell surface with a concentration at the cell periphery in the
      region occupied by focal adhesions. This aberrant localization correlated with
      reduced survival and alterations in normal focal adhesion and cytoskeleton
      morphology. This study therefore illustrates the critical role of the
      immunoglobulin domain in regulation of the localization of PTPmu and the
      importance of such control for the maintenance of normal cell physiology.

PMID- 15491995
TI  - Recognition of a basic AP-2 binding motif within the C2B domain of synaptotagmin
      is dependent on multimerization.
AB  - Synaptotagmin is a multifunctional membrane protein that may regulate exo
      endocytic cycling of synaptic vesicles at the presynaptic plasmalemma. Its C2B
      domain has been postulated to interact with a variety of effector molecules
      including acidic phospholipids, phosphoinositides, SNAREs (soluble N
      ethylmaleimide-sensitive factor attachment protein receptors), calcium channels,
      and the clathrin adaptor complex AP-2. Here we report that a basic motif within
      the C2B domain is required and sufficient for binding to AP-2 via its mu2 subunit
      and that this interaction is dependent on multimerization of the AP-2 binding
      site. Moreover, we show that upon fusion to a plasma membrane reporter protein
      this sequence is sufficient to target the chimeric molecule for internalization.
      We hypothesize that basic motifs within multimeric membrane proteins may
      represent a novel type of clathrin/AP-2-dependent endocytosis signal.

PMID- 15491994
TI  - SMRT and N-CoR corepressors are regulated by distinct kinase signaling pathways.
AB  - N-CoR and SMRT are corepressor paralogs that partner with and mediate
      transcriptional repression by a wide variety of metazoan transcription factors,
      including nuclear hormone receptors. Although encoded by distinct genetic loci, N
      CoR and SMRT share substantial sequence interrelatedness, form analogous
      assemblies with histone deacetylases and auxiliary factors, can interact with
      overlapping sets of transcription factor partners, and exert overlapping
      functions in cells. SMRT is subject to negative regulation by MAPK signaling
      pathways operating downstream of growth factor and stress signaling pathways. We
      report here that whereas activation of MEKK1 leads to phosphorylation of SMRT,
      its dissociation from its transcription factor partners in vivo and in vitro, and
      its redistribution from the cell nucleus to a cytoplasmic compartment, N-CoR is
      refractory to all these forms of regulation. In contrast to this MAPK cascade,
      other signal transduction pathways operating downstream of growth factor/cytokine
      receptors appear able to affect both corepressor paralogs. Our results indicate
      that SMRT and N-CoR are embedded in distinct regulatory networks and that the two
      corepressors interpret growth factor, cytokine, differentiation, and prosurvival
      signals differently.

PMID- 15491996
TI  - A family 8 glycoside hydrolase from Bacillus halodurans C-125 (BH2105) is a
      reducing end xylose-releasing exo-oligoxylanase.
AB  - The gene encoding family 8 glycoside hydrolases from Bacillus halodurans C-125
      (BH2105), an alkalophilic bacterium with a known genomic sequence, was expressed
      in Escherichia coli. The protein was expressed with the intact N-terminal
      sequence, suggesting that it did not possess a signal peptide and that it was an
      intracellular enzyme. The recombinant enzyme showed no hydrolytic activity on
      xylan, whereas it had been annotated as xylanase Y. It hydrolyzed
      xylooligosaccharide whose degree of polymerization is greater than or equal to 3
      in an exo-splitting manner with anomeric inversion, releasing the xylose unit at
      the reducing end. Judging from its substrate specificity and reaction mechanism,
      we named the enzyme reducing end xylose-releasing exo-oligoxylanase (Rex). Rex
      was found to utilize only the beta-anomer of the substrate to form beta-xylose
      and alpha-xylooligosaccharide. The optimum pH of the enzymatic reaction (6.2-7.3)
      was found in the neutral range, a range beneficial for intracellular enzymes. The
      genomic sequence suggests that B. halodurans secretes two endoxylanases and
      possesses two alpha-arabinofuranosidases, one alpha-glucuronidase, and three beta
      xylosidases intracellularly in addition to Rex. The extracellular enzymes
      supposedly hydrolyze xylan into arabino/glucurono-xylooligosaccharides that are
      then transported into the cells. Rex may play a role as a key enzyme in
      intracellular xylan metabolism in B. halodurans by cleaving xylooligosaccharides
      that were produced by the action of other intracellular enzymes from the
      arabino/glucurono-xylooligosaccharides.

PMID- 15491997
TI  - In vitro antibody evolution targeting germline hot spots to increase activity of
      an anti-CD22 immunotoxin.
AB  - Recombinant immunotoxin BL22, containing the Fv portion of an anti-CD22 antibody,
      produced complete remissions in most patients with drug-resistant hairy cell
      leukemia but had less activity in leukemias with low CD22 expression.
      Complementarity-determining region (CDR) mutagenesis is used to increase antibody
      affinity but can be difficult to perform successfully. We previously showed that
      antibodies with increased affinity and immunotoxins with increased activity could
      be obtained by directing mutations at specific DNA residues called hot spots.
      Because hot spots can arise either by somatic mutation or be present in the
      germline, we examined which type of hot spot is preferred for increasing antibody
      affinity. Initially, a second generation antibody phage-display library targeting
      a germline hot spot (Ser(30)-Asn(31)) within CDR1 of the antibody light chain was
      mutated. Substitution of serine 30 or asparagine 31 with arginine produced mutant
      immunotoxins with an affinity (0.8 nM) increased 7-fold over BL22 (5.8 nM) and 3
      fold over the first generation mutant HA22 (2.3 nM). More importantly, a 10-fold
      increase in activity over BL22 and a 2-3-fold increase over HA22 were observed in
      various B lymphoma cell lines including WSU-CLL that contains only 5500 CD22
      sites per cell. For comparison, two phage-display libraries targeting non
      germline hot spots in heavy chain CDR1 and CDR3 were generated but did not
      produce Fv with increased affinity. Our results demonstrate that germline hot
      spots but not non-germline hot spots are effective for in vitro antibody affinity
      maturation.

PMID- 15491998
TI  - Targeted disruption of MAIL, a nuclear IkappaB protein, leads to severe atopic
      dermatitis-like disease.
AB  - MAIL (molecule-possessing ankyrin repeats induced by lipopolysaccharide) is a
      nuclear IkappaB protein that is also termed interleukin-1-inducible nuclear
      ankyrin repeat protein or inhibitor of nuclear factor kappaB (IkappaB) zeta. In
      this study, we generated Mail-/- mice to investigate the roles of MAIL in whole
      organisms. Mail-/- mice grew normally until 4-8 weeks after birth, when they
      began to develop lesions in the skin of the periocular region, face, and neck.
      MAIL mRNA and protein were constitutively expressed in the skin of wild type
      controls, especially in the keratinocytes. Serum IgE was higher in Mail-/- mice
      than in normal. Histopathological analysis indicated that the Mail-/- skin
      lesions appeared to be atopic dermatitis (AD) eczema with inflammatory cell
      infiltration. In addition, markedly elevated expression of some chemokines such
      as thymus and activation-regulated chemokine was detected in the Mail-/- skin
      lesions, similar to that observed in the skin of patients with AD. In Mail-/-
      mice, MAIL-deficient keratinocytes might be activated to produce chemokines and
      induce intraepidermal filtration of inflammatory cells, resulting in the onset of
      the AD-like disease. These findings suggest that MAIL is an essential molecule
      for homeostatic regulation of skin immunity. The Mail-/- mouse is a valuable new
      animal model for research on AD.

PMID- 15491999
TI  - Genetic disruption of the Plasmodium falciparum digestive vacuole plasmepsins
      demonstrates their functional redundancy.
AB  - The digestive vacuole plasmepsins PfPM1, PfPM2, PfPM4, and PfHAP (a histoaspartic
      proteinase) are 4 aspartic proteinases among 10 encoded in the Plasmodium
      falciparum malarial genome. These have been hypothesized to initiate and
      contribute significantly to hemoglobin degradation, a catabolic function
      essential to the survival of this intraerythrocytic parasite. Because of their
      perceived significance, these plasmepsins have been proposed as potential targets
      for antimalarial drug development. To test their essentiality, knockout
      constructs were prepared for each corresponding gene such that homologous
      recombination would result in two partial, nonfunctional gene copies. Disruption
      of each gene was achieved, as confirmed by PCR, Southern, and Northern blot
      analyses. Western and two-dimensional gel analyses revealed the absence of mature
      or even truncated plasmepsins corresponding to the disrupted gene. Reduced growth
      rates were observed with PfPM1 and PfPM4 knockouts, indicating that although
      these plasmepsins are not essential, they are important for parasite development.
      Abnormal mitochondrial morphology also appeared to accompany loss of PfPM2, and
      an abundant accumulation of electron-dense vesicles in the digestive vacuole was
      observed upon disruption of PfPM4; however, those phenotypes only manifested in
      about a third of the disrupted cells. The ability to compensate for loss of
      individual plasmepsin function may be explained by close similarity in the
      structure and active site of these four vacuolar enzymes. Our data imply that
      drug discovery efforts focused on vacuolar plasmepsins must incorporate measures
      to develop compounds that can inhibit two or more of this enzyme family.

PMID- 15492000
TI  - Structural changes in the carboxyl terminus of the gap junction protein
      connexin43 indicates signaling between binding domains for c-Src and zonula
      occludens-1.
AB  - Regulation of cell-cell communication by the gap junction protein connexin43 can
      be modulated by a variety of connexin-associating proteins. In particular, c-Src
      can disrupt the connexin43 (Cx43)-zonula occludens-1 (ZO-1) interaction, leading
      to down-regulation of gap junction intercellular communication. The binding sites
      for ZO-1 and c-Src correspond to widely separated Cx43 domains (approximately 100
      residues apart); however, little is known about the structural modifications that
      may allow information to be transferred over this distance. Here, we have
      characterized the structure of the connexin43 carboxyl-terminal domain (Cx43CT)
      to assess its ability to interact with domains from ZO-1 and c-Src. NMR data
      indicate that the Cx43CT exists primarily as an elongated random coil, with two
      regions of alpha-helical structure. NMR titration experiments determined that the
      ZO-1 PDZ-2 domain affected the last 19 Cx43CT residues, a region larger than that
      reported to be required for Cx43CT-ZO-1 binding. The c-Src SH3 domain affected
      Cx43CT residues Lys-264-Lys-287, Ser-306-Glu-316, His-331-Phe-337, Leu-356-Val
      359, and Ala-367-Ser-372. Only region Lys-264-Lys-287 contains the residues
      previously reported to act as an SH3 binding domain. The specificity of these
      interactions was verified by peptide competition experiments. Finally, we
      demonstrated that the SH3 domain could partially displace the Cx43CT-PDZ-2
      complex. These studies represent the first structural characterization of a
      connexin domain when integrated in a multimolecular complex. Furthermore, we
      demonstrate that the structural characteristics of a disordered Cx43CT are
      advantageous for signaling between different binding partners that may be
      important in describing the mechanism of channel closure or internalization in
      response to pathophysiological stimuli.

PMID- 15492001
TI  - Parkin increases dopamine uptake by enhancing the cell surface expression of
      dopamine transporter.
AB  - Mutations of parkin, a protein-ubiquitin E3 ligase, are linked to Parkinson's
      disease (PD). Although a variety of parkin substrates have been identified, none
      of these is selectively expressed in dopaminergic neurons, whose degeneration
      plays a critical role in PD. Here we show that parkin significantly increased
      dopamine uptake in the human dopaminergic neuroblastoma cell line SH-SY5Y. This
      effect was accompanied by increased V(max) of dopamine uptake and unchanged K(m).
      Consistent with this, increased binding sites for dopamine transporter (DAT)
      ligand were observed in SH-SY5Y cells overexpressing parkin. The results were
      confirmed when parkin was transfected in HEK293 cells stably expressing DAT. In
      these cells, parkin enhanced the ubiquitination and degradation of DAT, increased
      its cell surface expression, and augmented dopamine uptake. The effects of parkin
      were significantly abrogated by its PD-causing mutations. Because the cell
      surface expression of functional DAT requires its oligomerization, misfolded DAT,
      induced either by the protein glycosylation inhibitor tunicamycin or by its C
      terminal truncation, significantly attenuated cell surface expression of native
      DAT and reduced dopamine uptake. Expression of parkin, but not its T240R mutant,
      significantly alleviated these detrimental effects of misfolded DAT. Thus, our
      studies suggest that parkin increases dopamine uptake by enhancing the
      ubiquitination and degradation of misfolded DAT, so as to prevent it from
      interfering with the oligomerization and cell surface expression of native DAT.
      This function of parkin would enhance the precision of dopaminergic transmission,
      increase the efficiency of dopamine utilization, and reduce dopamine toxicity on
      neighboring cells.

PMID- 15492002
TI  - Chemical modification of cysteine residues is a misleading indicator of their
      status as active site residues in the vitamin K-dependent gamma-glutamyl
      carboxylation reaction.
AB  - The enzymatic activity of the vitamin K-dependent proteins requires the post
      translational conversion of specific glutamic acids to gamma-carboxy-glutamic
      acid by the integral membrane enzyme, gamma-glutamyl carboxylase. Whether or not
      cysteine residues are important for carboxylase activity has been the subject of
      a number of studies. In the present study we used carboxylase with point
      mutations at cysteines, chemical modification, and mass spectrometry to examine
      this question. Mutation of any of the free cysteine residues to alanine or serine
      had little effect on carboxylase activity, although C343A mutant carboxylase had
      only 38% activity compared with that of wild type. In contrast, treatment with
      either thiol-reactive reagent 4-acetamido-4'-maleimidylstilbene-2,2'-disulfonic
      acid, disodium salt, or sodium tetrathionate, caused complete loss of activity.
      We identified the residues modified, using matrix-assisted laser
      desorption/ionization time of flight mass spectrometry, as Cys(323) and Cys(343).
      According to our results, these residues are on the cytoplasmic side of the
      microsomal membrane, whereas catalytic residues are expected to be on the lumenal
      side of the membrane. Carboxylase was partially protected from chemical
      modification by factor IXs propeptide. Although all mutant carboxylases bound
      propeptide with normal affinity, chemical modification caused a >100-fold
      decrease in carboxylase affinity for the consensus propeptide. We conclude that
      cysteine residues are not directly involved in carboxylase catalysis, but
      chemical modification of Cys(323) and Cys(343) may disrupt the three-dimensional
      structure, resulting in inactivation.

PMID- 15492003
TI  - GTP-dependent secretion from neutrophils is regulated by Cdk5.
AB  - We have previously shown evidence for the existence of a calcium-independent, GTP
      regulated mechanism of secretion from neutrophils, but this secretory mechanism
      remains to be fully elucidated. Cyclin-dependent kinase 5 (Cdk5), the various
      substrates of which include Munc18 and synapsin 1, has been implicated in
      neuronal secretion. Although the Cdk5 activator, p35, and Cdk5-p35 activity are
      primarily associated with neurons, we report here that p35 also exists in
      neutrophils and that an active Cdk5-p35 complex is present in these cells. Cdk5
      p35 activity in human neutrophils is mostly localized in secretory granules,
      which show an increase in Cdk5-p35 level and activity upon GTP stimulation. The
      potent Cdk5 inhibitor, roscovitine, completely blocks GTP-stimulated granule Cdk5
      activity, which accompanies lactoferrin secretion from neutrophil-specific
      granules. Roscovitine also inhibits GTP-induced lactoferrin secretion and surface
      localization of the secretion markers, CD63 and CD66b, to a certain extent.
      Furthermore, neutrophils from wild-type mice treated with roscovitine and
      neutrophils from p35(-/-) mice exhibit comparable surface expression levels of
      both CD63 and CD66b upon GTP stimulation. Although our data suggest that other
      molecules control GTP-induced secretion from neutrophils, it is clear that Cdk5
      p35 is required to elicit the maximum GTP-induced secretory response. Our
      observation that multiple proteins in neutrophil granules serve as specific
      substrates of Cdk5 further supports the premise that the kinase is a key
      component of the GTP-regulated secretory apparatus in neutrophils.

PMID- 15492004
TI  - Mutations of tubulin glycylation sites reveal cross-talk between the C termini of
      alpha- and beta-tubulin and affect the ciliary matrix in Tetrahymena.
AB  - Two types of polymeric post-translational modifications of alpha/beta-tubulin,
      glycylation and glutamylation, occur widely in cilia and flagella. Their
      respective cellular functions are poorly understood. Mass spectrometry and
      immunoblotting showed that two closely related species, the ciliates Tetrahymena
      and Paramecium, have dramatically different compositions of tubulin post
      translational modifications in structurally identical axonemes. Whereas the
      axonemal tubulin of Paramecium is highly glycylated and has a very low
      glutamylation content, the axonemal tubulin of Tetrahymena is glycylated and
      extensively glutamylated. In addition, only the alpha-tubulin of Tetrahymena
      undergoes detyrosination. Mutations of the known glycylation sites in Tetrahymena
      tubulin affected the level of each polymeric modification type in both the
      mutated and nonmutated subunits, revealing cross-talk between alpha- and beta
      tubulin. Ultrastructural analyses of glycylation site mutants uncovered defects
      in the doublet B-subfiber of axonemes and revealed an accumulation of dense
      material in the ciliary matrix, reminiscent of intraflagellar transport particles
      seen by others in Chlamydomonas. We propose that polyglycylation and/or
      polyglutamylation stabilize the B-subfiber of outer doublets and regulate the
      intraflagellar transport.

PMID- 15492006
TI  - G alpha 13 signals via p115RhoGEF cascades regulating JNK1 and primitive endoderm
      formation.
AB  - The heterotrimeric G-protein G(13) mediates the formation of primitive endoderm
      from mouse P19 embryonal carcinoma cells in response to retinoic acid, signaling
      to the level of activation of c-Jun N-terminal kinase. The signal linkage map
      from MEKK1/MEKK4 to MEK1/MKK4 to JNK is obligate in this G alpha(13)-mediated
      pathway, whereas that between G alpha(13) and MEKKs is not known. The overall
      pathway to primitive endoderm formation was shown to be inhibited by treatment
      with Clostridium botulinum C3 exotoxin, a specific inactivator of RhoA family
      members. Constitutively active G alpha(13) was found to activate RhoA as well as
      Cdc42 and Rac1 in these cells. Although constitutively active Cdc42, Rac1, and
      RhoA all can activate JNK1, only the RhoA mutant was able to promote formation of
      primitive endoderm, mimicking expression of the constitutively activated G
      alpha(13). Expression of the constitutively active mutant form of p115RhoGEF
      (guanine nucleotide exchange factor) was found to activate RhoA and JNK1
      activities. Expression of the dominant negative p115RhoGEF was able to inhibit
      activation of both RhoA and JNK1 in response to either retinoic acid or the
      expression of a constitutively activated mutant of G alpha(13). Expression of the
      dominant negative mutants of RhoA as well as those of either Cdc42 or Rac1, but
      not Ras, attenuated G alpha(13)-stimulated as well as retinoic acid-stimulated
      activation of all three of these small molecular weight GTPases, suggesting
      complex interrelationships among the three GTPases in this pathway. The formation
      of primitive endoderm in response to retinoic acid also could be blocked by
      expression of dominant negative mutants of RhoA, Cdc42, or Rac1. Thus, the signal
      propagated from G alpha(13) to JNK requires activation of p115RhoGEF cascades,
      including p115RhoGEF itself, RhoA, Cdc42, and Rac1. In a concerted effort, RhoA
      in tandem with Cdc42 and Rac1 activates the MEKK1/4, MEK1/MKK4, and JNK cascade,
      thereby stimulating formation of primitive endoderm.

PMID- 15492005
TI  - SHIP family inositol phosphatases interact with and negatively regulate the Tec
      tyrosine kinase.
AB  - The Tec family of protein-tyrosine kinases (PTKs), that includes Tec, Itk, Btk,
      Bmx, and Txk, plays an essential role in phospholipase Cgamma (PLCgamma)
      activation following antigen receptor stimulation. This function requires
      activation of phosphatidylinositol 3-kinase (PI 3-kinase), which promotes Tec
      membrane localization through phosphatidylinositol 3,4,5-trisphosphate (PtdIns
      3,4,5-P(3)) generation. The mechanism of negative regulation of Tec family PTKs
      is poorly understood. In this study, we show that the inositol 5' phosphatases
      SHIP1 and SHIP2 interact preferentially with Tec, compared with other Tec family
      members. Four lines of evidence suggest that SHIP phosphatases are negative
      regulators of Tec. First, SHIP1 and SHIP2 are potent inhibitors of Tec activity.
      Second, inactivation of the Tec SH3 domain, which is necessary and sufficient for
      SHIP binding, generates a hyperactive form of Tec. Third, SHIP1 inhibits Tec
      membrane localization. Finally, constitutively targeting Tec to the membrane
      relieves SHIP1-mediated inhibition. These data suggest that SHIP phosphatases can
      interact with and functionally inactivate Tec by de-phosphorylation of local
      PtdIns 3,4,5-P(3) and inhibition of Tec membrane localization.

PMID- 15492007
TI  - Interaction of thiostrepton and elongation factor-G with the ribosomal protein
      L11-binding domain.
AB  - Ribosomal protein L11 and the L11 binding region of ribosomal RNA constitute an
      important domain involved in active functions of the ribosome during translation.
      We studied the effects of L11 knock-out and truncation mutations on the structure
      of the rRNA in this region and on its interactions with a translation elongation
      factor and the antibiotic thiostrepton. The results indicated that the structure
      of the L11-binding rRNA becomes conformationally flexible when ribosomes lack the
      entire L11 protein, but not when the C-terminal domain is present on ribosomes.
      Probing wild type and mutant ribosomes in the presence of the antibiotic
      thiostrepton and elongation factor-G (EF-G) rigorously localized the binding
      cleft of thiostrepton and suggested a role for the rRNA in the L11-binding domain
      in modulating factor binding. Our results also provide evidence that the
      structure of the rRNA stabilized by the C-terminal domain of L11 is necessary to
      stabilize EF-G binding in the post-translocation state, and thiostrepton may
      modulate this structure in a manner that interferes with the ribosome-EF-G
      interaction. The implications for recent models of thiostrepton activity and
      factor interactions are discussed.

PMID- 15492008
TI  - Overexpression of mitogen-activated protein kinase kinase 6 in the heart improves
      functional recovery from ischemia in vitro and protects against myocardial
      infarction in vivo.
AB  - The mitogen-activated protein kinases (MAPK) have been the subject of many
      studies to identify signaling pathways that promote cell survival or death. In
      cultured cardiac myocytes, p38 MAPK promotes cell survival or death depending on
      whether it is activated by mitogen-activated protein kinase kinase 6 (MKK6) or
      MKK3, respectively. The objectives of the current study were to examine the
      effects of MKK6-mediated p38 activation in the heart in vivo. Accordingly, we
      generated transgenic (TG) mice that overexpress wild type MKK6 in a cardiac
      restricted manner. Although p38 was about 17-fold more active in TG than non
      transgenic (NTG) mouse hearts, TG mouse hearts were morphologically and
      functionally similar to those of NTG littermates. However, upon transient
      ischemia followed by reperfusion, the MKK6 TG mouse hearts exhibited
      significantly better functional recovery and less injury than NTG mouse hearts.
      Because MKK6 increases levels of the protective small heat shock protein, alpha B
      crystallin (alpha BC), in cultured cardiac myocytes, we examined alpha BC levels
      in the mouse hearts. The level of alpha BC was 2-fold higher in MKK6 TG than NTG
      mouse hearts. Moreover, ischemia followed by reperfusion induced a 6.4-fold
      increase in alpha BC levels in the mitochondrial fractions of TG mouse hearts but
      no increase in alpha BC levels in any of the other fractions analyzed. These
      alterations in alpha BC expression and localization suggest possible mechanisms
      of cardioprotection in MKK6 TG mouse hearts.

PMID- 15492009
TI  - Stretch-inducible expression of the angiogenic factor CCN1 in vascular smooth
      muscle cells is mediated by Egr-1.
AB  - CCN1 is an angiogenic factor that promotes cell adhesion, proliferation, and
      differentiation. CCN1-deficient mice suffer embryonic death because of vascular
      defects, demonstrating that CCN1 is required for vessel development. Because
      mechanical stretch may act as a trigger for vessel development, we investigated
      the impact of mechanical stretch on the regulatory mechanism of CCN1 expression.
      Mechanical stretch rapidly enhances CCN1 expression and release in vascular
      smooth muscle cells (VSMC) in vitro and CCN1 expression in murine aortic segments
      in vivo. Transfection experiments of VSMC with deletion constructs of the CCN1
      promoter revealed the regulatory region responsible for the stretch-induced CCN1
      expression in the approximately 200-bp promoter region upstream of the TATA-box
      containing potential binding sites for early growth response-1 (Egr-1), nuclear
      factor of activated T-cells and cAMP response element binding protein. Decoy
      oligonucleotides to Egr-1, but not to nuclear factor of activated T-cells or cAMP
      response element binding protein, abolished the stretch-induced transcription of
      CCN1. In addition, mutagenesis of the Egr-1 binding site within the CCN1 promoter
      completely blunted the stretch-induced activation of the promoter. Furthermore,
      mechanical stretch induced the expression and DNA-binding activity of Egr-1 in
      VSMC as demonstrated by Western blot and electromobility shift assay. Moreover, a
      pressure overload-dependent de novo synthesis of Egr-1 was observed after aortic
      banding. These findings indicate that mechanical stretch leads to enhanced
      expression of CCN1 via the mechanosensitive transcription factor Egr-1,
      suggesting a central role for mechanical stretch in the regulation of CCN1
      dependent pro-angiogenic potency.

PMID- 15492010
TI  - Chaperone activity and prodan binding at the self-associating domain of erythroid
      spectrin.
AB  - Spectrin, the major constituent protein of the erythrocyte membrane skeleton,
      exhibits chaperone activity by preventing the irreversible aggregation of insulin
      at 25 degrees C and that of alcohol dehydrogenase at 50 degrees C. The dimeric
      spectrin and the two subunits, alpha-spectrin and beta-spectrin prevent such
      aggregation appreciably better, 70% in presence of dimeric spectrin at an
      insulin:spectrin ratio of 1:1, than that in presence of the tetramer of 25%. Our
      results also show that spectrin binds to denatured enzymes alpha-glucosidase and
      alkaline phosphatase during refolding and the reactivation yields are increased
      in the presence of the spectrin derivatives when compared with those refolded in
      their absence. The unique hydrophobic binding site on spectrin for the
      fluorescence probe, 6-propionyl-2-(dimethylamino)naphthalene (Prodan) has been
      established to localize at the self-associating domain with the binding
      stoichiometry of one Prodan/both dimeric and tetrameric spectrin. The other
      fluorescence probe, 1-anilinonaphthalene-8-sulfonic acid, does not show such
      specificity for spectrin, and the binding stoichiometry is between 3 and 5 1
      anilinonaphthalene-8-sulfonic acid/dimeric and tetrameric spectrin, respectively.
      Regions in alpha- and beta-spectrins have been found to have sequence homology
      with known chaperone proteins. More than 50% similarities in alpha-spectrin near
      the N terminus with human Hsp90 and in beta-spectrin near the C terminus with
      human Hsp90 and Escherichia coli DnaJ have been found, indicating a potential
      chaperone-like sequence to be present near the self-associating domain that is
      formed by portions of alpha-spectrin near the N terminus and the beta-spectrin
      near the C terminus. There are other patches of sequences also in both the
      spectrin polypeptides, at the other termini as well as in the middle of the rod
      domain having significant homology with well known chaperone proteins.

PMID- 15492011
TI  - Identification of a novel serum response factor cofactor in cardiac gene
      regulation.
AB  - The transcription factor serum response factor (SRF) plays an important role in
      the regulation of a variety of cardiac genes during development and during adult
      aging. A novel SRF cofactor, herein called p49/STRAP, for SRF-dependent
      transcription regulation-associated protein, was recently identified in our
      laboratory. This protein interacted mainly with the transcriptional activation
      domain of the SRF protein and was found to bind to SRF or to the complex of SRF
      and another cofactor, such as myocardin or Nkx2.5. The expression of p49/STRAP
      affected the promoter activity of SRF target genes in a non-uniform manner. For
      example, p49 activated MLC2v and cardiac actin promoters when it was co
      transfected with SRF, but it repressed atrial natriuretic factor promoter
      activity, which was strongly induced by myocardin. The p49/STRAP mRNA was
      observed to be highly expressed in fetal, adult, and senescent human hearts, and
      also in hearts of young adult and old mice, suggesting that p49/STRAP may be an
      important SRF cofactor in the transcriptional regulation of mammalian cardiac
      muscle genes throughout the life span.

PMID- 15492012
TI  - Cdc42 regulates arsenic-induced NADPH oxidase activation and cell migration
      through actin filament reorganization.
AB  - Although arsenic is a human carcinogen, the molecular mechanisms of its action
      remain to be understood. The present study reports that exposure to arsenic
      induced actin filament reorganization, resulting in lamellipodia and filopodia
      structures through the activation of Cdc42 in SVEC4-10 endothelial cells. It was
      also found that arsenic induced the formation of the superoxide anion (O2*) in
      SVEC4-10 cells. Immunoprecipitation and Western blotting analysis demonstrated
      that arsenic stimulation induced serine phosphorylation of p47phox, a key
      component of NADPH oxidase, indicating that arsenic induces O2* formation through
      NADPH oxidase activation. Inhibition of arsenic-induced actin filament
      reorganization by either overexpression of a dominant negative Cdc42 or
      pretreatment of an actin filament stabilizing regent, jasplakinolide, abrogated
      arsenic-induced NADPH oxidase activation, showing that the activation of NADPH
      oxidase was regulated by Cdc42-mediated actin filament reorganization. This study
      also showed that overexpression of a dominant negative Rac1 was sufficient to
      abolish arsenic-induced O2*- production, implying that Rac1 activities are
      required for Cdc42-mediated NADPH oxidase activation in response to arsenic
      stimulation. Furthermore, arsenic stimulation induced cell migration, which can
      be inhibited by the inactivation of either Cdc42 or NADPH oxidase. Taken
      together, the results indicate that arsenic is able to activate NADPH oxidase
      through Cdc42-mediated actin filament reorganization, leading to the induction of
      an increase in cell migration in SVEC4-10 endothelial cells.

PMID- 15492013
TI  - Crystal structure of mouse carnitine octanoyltransferase and molecular
      determinants of substrate selectivity.
AB  - Carnitine acyltransferases have crucial functions in fatty acid metabolism.
      Members of this enzyme family show distinctive substrate preferences for short-,
      medium- or long-chain fatty acids. The molecular mechanism for this substrate
      selectivity is not clear as so far only the structure of carnitine
      acetyltransferase has been determined. To further our understanding of these
      important enzymes, we report here the crystal structures at up to 2.0-A
      resolution of mouse carnitine octanoyltransferase alone and in complex with the
      substrate octanoylcarnitine. The structures reveal significant differences in the
      acyl group binding pocket between carnitine octanoyltransferase and carnitine
      acetyltransferase. Amino acid substitutions and structural changes produce a
      larger hydrophobic pocket that binds the octanoyl group in an extended
      conformation. Mutation of a single residue (Gly-553) in this pocket can change
      the substrate preference between short- and medium-chain acyl groups. The side
      chains of Cys-323 and Met-335 at the bottom of this pocket assume dual
      conformations in the substrate complex, and mutagenesis studies suggest that the
      Met-335 residue is important for catalysis.

PMID- 15492014
TI  - Structural basis of 5-nitroimidazole antibiotic resistance: the crystal structure
      of NimA from Deinococcus radiodurans.
AB  - 5-Nitroimidazole-based antibiotics are compounds extensively used for treating
      infections in humans and animals caused by several important pathogens. They are
      administered as prodrugs, and their activation depends upon an anaerobic 1
      electron reduction of the nitro group by a reduction pathway in the cells.
      Bacterial resistance toward these drugs is thought to be caused by decreased drug
      uptake and/or an altered reduction efficiency. One class of resistant strains,
      identified in Bacteroides, has been shown to carry Nim genes (NimA, -B, -C, -D,
      and -E), which encode for reductases that convert the nitro group on the
      antibiotic into a non-bactericidal amine. In this paper, we have described the
      crystal structure of NimA from Deinococcus radiodurans (drNimA) at 1.6 A
      resolution. We have shown that drNimA is a homodimer in which each monomer adopts
      a beta-barrel fold. We have identified the catalytically important His-71 along
      with the cofactor pyruvate and antibiotic binding sites, all of which are found
      at the monomer-monomer interface. We have reported three additional crystal
      structures of drNimA, one in which the antibiotic metronidazole is bound to the
      protein, one with pyruvate covalently bound to His-71, and one with lactate
      covalently bound to His-71. Based on these structures, a reaction mechanism has
      been proposed in which the 2-electron reduction of the antibiotic prevents
      accumulation of the toxic nitro radical. This mechanism suggests that Nim
      proteins form a new class of reductases, conferring resistance against 5
      nitroimidazole-based antibiotics.

PMID- 15492015
TI  - Interleukin-10 mediates the protective effect of Linomide by reducing CXC
      chemokine production in endotoxin-induced liver injury.
AB  - The immunomodulator Linomide has been shown to protect against septic liver
      injury by reducing hepatic accumulation of leukocytes although the detailed anti
      inflammatory mechanisms remain elusive. This study examined the effect of
      Linomide on the production of CXC chemokines, including macrophage inflammatory
      protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (KC) and
      interleukin-10 (IL-10) in lipopolysaccharide (LPS)/d-galactosamine (Gal)-induced
      liver injury in mice. It was found that pretreatment with 300 mg kg(-1) of
      Linomide markedly suppressed leukocyte recruitment, perfusion failure, and
      hepatocellular damage and apoptosis in the liver of endotoxemic mice.
      Administration of Linomide inhibited endotoxin-induced gene expression of MIP-2
      and KC and significantly reduced the hepatic production of MIP-2 and KC by 63 and
      80%, respectively. Moreover, it was found that Linomide increased the liver
      content of IL-10 by more than three-fold in endotoxemic mice. The protective
      effect of Linomide against endotoxin-induced inflammation and liver injury was
      abolished in IL-10-deficient mice, suggesting that the beneficial effect of
      Linomide is dependent on the function of IL-10. Taken together, these novel
      findings suggest that the protective effect of Linomide is mediated via local
      upregulation of IL-10, which in turn decreases the generation of CXC chemokines
      and pathological recruitment of leukocytes in the liver of endotoxemic mice.

PMID- 15492016
TI  - Platelet--cancer interactions: mechanisms and pharmacology of tumour cell-induced
      platelet aggregation.
AB  - During haematogenous metastasis, cancer cells migrate to the vasculature and
      interact with platelets resulting in tumour cell-induced platelet aggregation
      (TCIPA). We review: 1. The biological and clinical significance of TCIPA; 2.
      Molecular mechanisms involved in platelet aggregation by cancer cells; 3.
      Strategies for pharmacological regulation of these interactions. We conclude that
      pharmacological regulation of platelet-cancer cell interactions may reduce the
      impact of TCIPA on cancer biology.

PMID- 15492017
TI  - Lipopolysaccharide fever is initiated via a capsaicin-sensitive mechanism
      independent of the subtype-1 vanilloid receptor.
AB  - As pretreatment with intraperitoneal capsaicin (8-methyl-N-vanillyl-6-nonenamide,
      CAP), an agonist of the vanilloid receptor known as VR1 or transient receptor
      potential channel-vanilloid receptor subtype 1 (TRPV-1), has been shown to block
      the first phase of lipopolysaccharide (LPS) fever in rats, this phase is thought
      to depend on the TRPV-1-bearing sensory nerve fibers originating in the abdominal
      cavity. However, our recent studies suggest that CAP blocks the first phase via a
      non-neural mechanism. In the present work, we studied whether this mechanism
      involves the TRPV-1. Adult Long-Evans rats implanted with chronic jugular
      catheters were used. Pretreatment with CAP (5 mg kg(-1), i.p.) 10 days before
      administration of LPS (10 microg kg(-1), i.v.) resulted in the loss of the entire
      first phase and a part of the second phase of LPS fever. Pretreatment with the
      ultrapotent TRPV-1 agonist resiniferatoxin (RTX; 2, 20, or 200 microg kg(-1),
      i.p.) 10 days before administration of LPS had no effect on the first and second
      phases of LPS fever, but it exaggerated the third phase at the highest dose. The
      latter effect was presumably due to the known ability of high doses of TRPV-1
      agonists to cause a loss of warm sensitivity, thus leading to uncontrolled,
      hyperpyretic responses. Pretreatment with the selective competitive TRPV-1
      antagonist capsazepine (N-[2-(4-chlorophenyl)ethyl]-1,3,4,5-tetrahydro-7,8
      dihydroxy-2H-2-benzazepine-2-carbothioamidem, CPZ; 40 mg kg(-1), i.p.) 90 min
      before administration of LPS (10 microg kg(-1), i.v.) or CAP (1 mg kg(-1), i.p.)
      did not affect LPS fever, but blocked the immediate hypothermic response to acute
      administration of CAP. It is concluded that LPS fever is initiated via a non
      neural mechanism, which is CAP-sensitive but RTX- and CPZ-insensitive. The action
      of CAP on this mechanism is likely TRPV-1-independent. It is speculated that this
      mechanism may be the production of prostaglandin E(2) by macrophages in LPS
      processing organs.

PMID- 15492018
TI  - A Na+ channel agonist: a potential cardiotonic agent with a novel mechanism?

PMID- 15492019
TI  - Inhibition of monoacylglycerol lipase and fatty acid amide hydrolase by analogues
      of 2-arachidonoylglycerol.
AB  - The pharmacology of monoacylglycerol lipase (MAGL) is not well understood. In
      consequence, the abilities of a series of analogues of 2-arachidonoylglycerol (2
      AG) to inhibit cytosolic 2-oleoylglycerol and membrane-bound anandamide hydolysis
      by MAGL and fatty acid amide hydrolase (FAAH), respectively, have been
      investigated. 2-AG and its 1-regioisomer (1-AG) interacted with MAGL with similar
      affinities (IC(50) values 13 and 17 mum, respectively). Shorter homologues of 2
      AG (2-linoleoylglycerol and 2-oleoylglycerol) had affinities for MAGL similar to
      2-AG. This pattern was also seen when the arachidonoyl side chain of arachidonoyl
      trifluoromethylketone was replaced by an oleoyl side chain. Arachidonoyl serinol
      (IC(50) value 73 microM) was a weaker inhibitor of MAGL than 2-AG. The IC(50)
      values of noladin ether towards MAGL and FAAH were 36 and 3 microM, respectively.
      Arachidonoyl glycine interacted with FAAH (IC(50) value 4.9 microM) but only
      weakly interacted with MAGL (IC(50) value >100 microM). alpha-Methyl-1-AG had
      similar potencies towards MAGL and FAAH (IC(50) values of 11 and 33 microM,
      respectively). O-2203 (1-(20-cyano-16,16-dimethyl-eicosa-5,8,11,14-tetraenoyl)
      glycerol) and O-2204 (2-(20-hydroxy-16,16-dimethyl-eicosa-5,8,11,14-tetraenoyl)
      glycerol) were slightly less potent, but again affected both enzymes equally.
      alpha-Methyl-1-AG, O-2203 and O-2204 interacted only weakly with cannabinoid
      CB(1) receptors expressed in CHO cells (K(i) values 1.8, 3.7 and 3.2 microM,
      respectively, compared with 0.24 microM for 1-AG) and showed no evidence of
      central cannabinoid receptor activation in vivo at doses up to 30 mg kg(-1) i.v.
      It is concluded that compounds like alpha-Methyl-1-AG, O-2203 and O-2204 may be
      useful as leads for the discovery of selective MAGL inhibitors that lack direct
      effects upon cannabinoid receptors.

PMID- 15492021
TI  - In vivo apoptosis of diabetogenic T cells in NOD mice by IFN-gamma/TNF-alpha.
AB  - Immunization with mycobacterial preparation such as Bacille Calmette-Guerin (BCG)
      or complete Freund's adjuvant (CFA) prevents the onset and recurrence of type 1
      diabetes in non-obese diabetic (NOD) mice. In this study, we explored the
      mechanism underlying the down-regulation of diabetogenic T cells by BCG
      treatment. We found that the potential of splenocytes from BCG-immunized diabetic
      NOD mice to adoptively transfer diabetes was significantly impaired. BCG
      immunization sequentially induced the production of TNF-alpha, IFN-gamma and IL-4
      by splenocytes, increased the expression of Fas(high) (Apo-1/CD95), Fas ligand
      (FasL, CD95L) and TNF receptor (TNFR) on T cells leading to T cell apoptosis. The
      primary role of IFN-gamma and TNF-alpha in BCG-immunotherapy was demonstrated by
      (i) reversing the immune regulatory effect of BCG by in vivo treatment with
      neutralizing anti-cytokine antibodies, (ii) inducing effect similar to BCG by
      treatment with these cytokines. We show that Fas and TNF are two pathways in BCG
      induced apoptosis of diabetogenic T cells, since in vitro blocking FasL or TNFR1
      with antibody reduced T cell apoptosis and increased T cell proliferative
      response. In addition, TNF-alpha and agonistic anti-Fas antibody had a
      synergistic effect on the in vitro apoptosis of diabetogenic T cells. Our results
      suggest that BCG down-regulates destructive autoimmunity by TNF-alpha/IFN-gamma
      induced apoptosis of diabetogenic T cells through both Fas and TNF pathways.
      These studies provide a novel mechanism for blocking disease recurrence and
      immune modulating effect of BCG immunization in type 1 diabetes.

PMID- 15492020
TI  - Multidrug transporter activity in lymphocytes.
AB  - Multidrug transporters play a dual role in haematopoietic cells, mediating the
      efflux of xenobiotics and regulating cell migration. For several reasons
      including the lack of specific antibodies, reports of multidrug transporter
      distribution on lymphocytes conflict. Murine B cells have been reported to
      completely lack transporter activity. Through analysis of parental and 'knockout'
      mice we show that, contrary to previous studies, murine B and T lymphocytes
      possess at least three active multidrug transporters and also a hitherto
      unrecognised drug-specific import activity. Surprisingly, the drug specificity of
      P-glycoprotein appears cell type dependent. The data indicate that a range of
      developmentally regulated, multidrug transporters can impose a barrier to
      treatment of immune disorders.

PMID- 15492022
TI  - Kinetic assessment of general gene expression changes during human naive CD4+ T
      cell activation.
AB  - The consequence of naive CD4+ T cell activation is the differentiation and
      generation of effector cells. How the engagement of T cell receptors and co
      stimulatory receptors leads to profound differential changes is not fully
      understood. To assess the transcription changes during T cell activation, we
      developed human T cell specific cDNA microarray gene filters and examined the
      gene expression profiles in human naive CD4+ T cells for 10 continuous time
      points during the first 24 h after anti-CD3 plus anti-CD28 (anti-CD3/CD28)
      stimulation. We report here a global and kinetic analysis of gene expression
      changes during naive CD4+ T cell activation and identify 196 genes having
      expression levels that significantly changed after activation. Based on the
      temporal change, there are 15 genes that changed between 0-1 h (early), 25 genes
      between 2-8 h (middle) and 156 genes between 16-24 h (late) after stimulation.
      Further analyses of the functions of those genes indicate their roles in
      maintenance of resting status, activation, adhesion/migration, cell cycle
      progression and cytokine production. However, a significant majority of these
      genes are novel to T cells and their functions in T cell activation require
      further study. Together, these results present a kinetic view of the gene
      expression changes of naive CD4+ T cells in response to T cell receptor-mediated
      activation for the first time, and provide a basis in understanding how the
      complex network of gene expression regulation is programmed during CD4+ T cell
      activation.

PMID- 15492023
TI  - Oviduct prostacyclin functions as a paracrine factor to augment the development
      of embryos.
AB  - BACKGROUND: Recently we discovered that human oviducts produce a significant
      amount of prostacyclin (prostaglandin I2, PGI2) and that PGI2 enhances the
      potentials of live birth of mouse embryos. However, the eicosanoid profile of
      mouse oviducts remains unknown. METHODS: The metabolites of [14C]arachidonic acid
      by mouse oviducts were analysed by high-performance liquid chromatography. The
      expression of cyclooxygenase (COX)-1, COX-2 and PGI2 synthase (PGIS) was analysed
      by western blot analysis and immunohistochemistry. The PGI2 synthetic capacities
      and the COX transcripts during the preimplantation period were compared. The
      effects of COX-2 inhibitor on PGI2 production were ascertained. RESULTS: Mouse
      oviducts produced, in order of abundance, PGI2, PGD2 and PGE2. Western blot
      analysis confirmed the expression of COX-1, -2 and PGIS which were expressed by
      luminal epithelia and smooth muscle cells. Day 2-3 post-coitus (p.c.) oviducts
      produced PGI2 10-fold higher than day 4 p.c. oviducts (P = 0.0087); day 1 p.c.
      oviducts expressed COX-2 transcript 5-fold higher than day 3 p.c. oviducts (P =
      0.0004). The PGI2 production was markedly reduced by a selective COX-2 inhibitor.
      CONCLUSIONS: Mouse oviducts synthesized maximal PGI2 during day 2-3 p.c.,
      coinciding with the transformation of 2-cell embryos to morulae. The results
      suggest that oviduct-derived PGI2 may enhance embryo development in a paracrine
      fashion.

PMID- 15492024
TI  - Should diagnostic testicular sperm retrieval followed by cryopreservation for
      later ICSI be the procedure of choice for all patients with non-obstructive
      azoospermia?
AB  - BACKGROUND: This was a retrospective study to determine if diagnostic testicular
      biopsy followed by cryopreservation should be the procedure of choice for all
      patients with testicular failure. METHODS: The first part of the study analysed
      97 ICSI cycles scheduled with frozen-thawed testicular sperm for 69 non
      obstructive azoospermia (NOA) patients. The second part focused on a subgroup of
      32 patients who underwent 42 ICSI cycles with frozen and 44 cycles with fresh
      testicular sperm. Sperm characteristics, fertilization, embryo quality, pregnancy
      and implantation rates were evaluated. RESULTS: Part I: The average time needed
      to find sperm was 113 min per cycle and 17 min per individual sperm.
      Fertilization rate, embryo transfer rate, ongoing pregnancy and implantation
      rates were 58.4%, 83%, 20.8% and 11.3%, respectively. Part II: The search time
      per sperm was higher (P=0.016) in frozen (18 min) than in fresh suspensions (13
      min). A higher embryo transfer rate was observed in fresh cycles than in frozen
      cycles (93.2% vs 76.2%, P=0.028). Fertilization, ongoing pregnancy and
      implantation rates were comparable for the two groups. CONCLUSIONS: Even in a
      programme with low-restrictive criteria for patient allocation and for sperm
      cryopreservation, diagnostic testicular biopsy followed by cryopreservation can
      be the procedure of choice for patients with testicular failure.

PMID- 15492027
TI  - Factors and forces affecting EHR system adoption: report of a 2004 ACMI
      discussion.
AB  - After the first session of the American College of Medical Informatics 2004
      retreat, during which the history of electronic health records was reviewed, the
      second session served as a forum for discussion about the state of the art of EHR
      adoption. Adoption and diffusion rates for both inpatient and outpatient EHRs are
      low for a myriad of reasons ranging from personal physician concerns about
      workflow to broad environmental issues. Initial recommendations for addressing
      these issues include providing communication and education to both providers and
      consumers and alignment of incentives for clinicians.

PMID- 15492028
TI  - Accelerating U.S. EHR adoption: how to get there from here. recommendations based
      on the 2004 ACMI retreat.
AB  - Despite growing support for the adoption of electronic health records (EHR) to
      improve U.S. healthcare delivery, EHR adoption in the United States is slow to
      date due to a fundamental failure of the healthcare information technology
      marketplace. Reasons for the slow adoption of healthcare information technology
      include a misalignment of incentives, limited purchasing power among providers,
      variability in the viability of EHR products and companies, and limited
      demonstrated value of EHRs in practice. At the 2004 American College of Medical
      Informatics (ACMI) Retreat, attendees discussed the current state of EHR adoption
      in this country and identified steps that could be taken to stimulate adoption.
      In this paper, based upon the ACMI retreat, and building upon the experiences of
      the authors developing EHR in academic and commercial settings we identify a set
      of recommendations to stimulate adoption of EHR, including financial incentives,
      promotion of EHR standards, enabling policy, and educational, marketing, and
      supporting activities for both the provider community and healthcare consumers.

PMID- 15492029
TI  - Will the wave finally break? A brief view of the adoption of electronic medical
      records in the United States.
AB  - For over thirty years, there have been predictions that the widespread clinical
      use of computers was imminent. Yet the "wave" has never broken. In this article,
      two broad time periods are examined: the 1960's to the 1980's and the 1980's to
      the present. Technology immaturity, health administrator focus on financial
      systems, application "unfriendliness," and physician resistance were all barriers
      to acceptance during the early time period. Although these factors persist,
      changes in clinicians' economics, more computer literacy in the general
      population, and, most importantly, changes in government policies and increased
      support for clinical computing suggest that the wave may break in the next
      decade.

PMID- 15492030
TI  - An evaluation of the current state of genomic data privacy protection technology
      and a roadmap for the future.
AB  - The incorporation of genomic data into personal medical records poses many
      challenges to patient privacy. In response, various systems for preserving
      patient privacy in shared genomic data have been developed and deployed. Although
      these systems de-identify the data by removing explicit identifiers (e.g., name,
      address, or Social Security number) and incorporate sound security design
      principles, they suffer from a lack of formal modeling of inferences learnable
      from shared data. This report evaluates the extent to which current protection
      systems are capable of withstanding a range of re-identification methods,
      including genotype-phenotype inferences, location-visit patterns, family
      structures, and dictionary attacks. For a comparative re-identification analysis,
      the systems are mapped to a common formalism. Although there is variation in
      susceptibility, each system is deficient in its protection capacity. The author
      discovers patterns of protection failure and discusses several of the reasons why
      these systems are susceptible. The analyses and discussion within provide
      guideposts for the development of next-generation protection methods amenable to
      formal proofs.

PMID- 15492031
TI  - The PING personally controlled electronic medical record system: technical
      architecture.
AB  - Despite progress in creating standardized clinical data models and
      interapplication protocols, the goal of creating a lifelong health care record
      remains mired in the pragmatics of interinstitutional competition, concerns about
      privacy and unnecessary disclosure, and the lack of a nationwide system for
      authenticating and authorizing access to medical information. The authors
      describe the architecture of a personally controlled health care record system,
      PING, that is not institutionally bound, is a free and open source, and meets the
      policy requirements that the authors have previously identified for health care
      delivery and population-wide research.

PMID- 15492032
TI  - A high productivity/low maintenance approach to high-performance computation for
      biomedicine: four case studies.
AB  - The rapid advances in high-throughput biotechnologies such as DNA microarrays and
      mass spectrometry have generated vast amounts of data ranging from gene
      expression to proteomics data. The large size and complexity involved in
      analyzing such data demand a significant amount of computing power. High
      performance computation (HPC) is an attractive and increasingly affordable
      approach to help meet this challenge. There is a spectrum of techniques that can
      be used to achieve computational speedup with varying degrees of impact in terms
      of how drastic a change is required to allow the software to run on an HPC
      platform. This paper describes a high- productivity/low-maintenance (HP/LM)
      approach to HPC that is based on establishing a collaborative relationship
      between the bioinformaticist and HPC expert that respects the former's codes and
      minimizes the latter's efforts. The goal of this approach is to make it easy for
      bioinformatics researchers to continue to make iterative refinements to their
      programs, while still being able to take advantage of HPC. The paper describes
      our experience applying these HP/LM techniques in four bioinformatics case
      studies: (1) genome-wide sequence comparison using Blast, (2) identification of
      biomarkers based on statistical analysis of large mass spectrometry data sets,
      (3) complex genetic analysis involving ordinal phenotypes, (4) large-scale
      assessment of the effect of possible errors in analyzing microarray data. The
      case studies illustrate how the HP/LM approach can be applied to a range of
      representative bioinformatics applications and how the approach can lead to
      significant speedup of computationally intensive bioinformatics applications,
      while making only modest modifications to the programs themselves.

PMID- 15492033
TI  - Implementation of hospital computerized physician order entry systems in a rural
      state: feasibility and financial impact.
AB  - OBJECTIVE: The aim of this study was to estimate the costs of implementing
      computerized physician order entry (CPOE) systems in hospitals in a rural state
      and to evaluate the financial implications of statewide CPOE implementation.
      METHODS: A simulation model was constructed using estimates of initial and
      ongoing CPOE costs mapped onto all general hospitals in Iowa by bed quantity and
      current clinical information system (CIS) status. CPOE cost estimates were
      obtained from a leading CPOE vendor. Current CIS status was determined through
      mail survey of Iowa hospitals. Patient care revenue and operating cost data
      published by the Iowa Hospital Association were used to simulate the financial
      impact of CPOE adoption on hospitals. RESULTS: CPOE implementation would
      dramatically increase operating costs for rural and critical access hospitals in
      the absence of substantial costs savings associated with improved efficiency or
      improved patient safety. For urban and rural referral hospitals, the cost impact
      is less dramatic but still substantial. However, relatively modest benefits in
      the form of patient care cost savings or revenue enhancement would be sufficient
      to offset CPOE costs for these larger hospitals. CONCLUSION: Implementation of
      CPOE in rural or critical access hospitals may depend on net increase in
      operating costs. Adoption of CPOE may be financially infeasible for these small
      hospitals in the absence of increases in hospital payments or ongoing subsidies
      from third parties.

PMID- 15492034
TI  - Generating XML schemas for DICOM structured reporting templates.
AB  - In this paper, the authors describe a methodology to transform programmatically
      structured reporting (SR) templates defined by the Digital Imaging and
      Communications for Medicine (DICOM) standard into an XML schema representation.
      Such schemas can be used in the creation and validation of XML-encoded SR
      documents that use templates. Templates are a means to put additional constraints
      on an SR document to promote common formats for specific reporting applications
      or domains. As the use of templates becomes more widespread in the production of
      SR documents, it is important to ensure validity of such documents. The work
      described in this paper is an extension of the authors' previous work on XML
      schema representation for DICOM SR. Therefore, this paper inherits and partially
      modifies the structure defined in the earlier work.

PMID- 15492036
TI  - Safe teleradiology: information assurance as project planning methodology.
AB  - The Georgetown University Medical Center Department of Radiology used a tailored
      version of OCTAVE, a self-directed information security risk assessment method,
      to design a teleradiology system that complied with the regulation implementing
      the security provisions of the Health Insurance Portability and Accountability
      Act (HIPAA) of 1996. The system addressed threats to and vulnerabilities in the
      privacy and security of protected health information. By using OCTAVE, Georgetown
      identified the teleradiology program's critical assets, described threats to the
      assurance of those assets, developed and ran vulnerability scans of a system
      pilot, evaluated the consequences of security breaches, and developed a risk
      management plan to mitigate threats to program assets, thereby implementing good
      information assurance practices. This case study illustrates the basic point that
      prospective, comprehensive planning to protect the privacy and security of an
      information system strategically benefits program management as well as system
      security.

PMID- 15492035
TI  - VA QUERI informatics paper: information technology for clinical guideline
      implementation: perceptions of multidisciplinary stakeholders.
AB  - OBJECTIVE: This multisite study compared the perceptions of three stakeholder
      groups regarding information technologies as barriers to and facilitators of
      clinical practice guidelines (CPGs). DESIGN: The study settings were 18 U.S.
      Veterans Affairs Medical Centers. A purposive sample of 322 individuals
      participated in 50 focus groups segmented by profession and included
      administrators, physicians, and nurses. Focus group participants were selected
      based on their knowledge of practice guidelines and involvement in facility-wide
      guideline implementation. MEASUREMENTS: Descriptive content analysis of 1,500
      pages of focus group transcripts. RESULTS: Eighteen themes clustered into four
      domains. Stakeholders were similar in discussing themes in the computer function
      domain most frequently but divergent in other domains, with workplace factors
      more often discussed by administrators, system design issues discussed most by
      nurses, and personal concerns discussed by physicians and nurses. Physicians and
      nurses most often discussed barriers, whereas administrators focused most often
      on facilitation. Facilitators included guideline maintenance and charting
      formats. Barriers included resources, attitudes, time and workload, computer
      glitches, computer complaints, data retrieval, and order entry. Themes with dual
      designations included documentation, patient records, decision support,
      performance evaluation, CPG implementation, computer literacy, essential data,
      and computer accessibility. CONCLUSION: Stakeholders share many concerns
      regarding the relationships between information technologies and clinical
      guideline use. However, administrators, physicians, and nurses hold different
      opinions about specific facilitators and barriers. Health professionals'
      disparate perceptions could undermine guideline initiatives. Implementation plans
      should specifically incorporate actions to address these barriers and enhance the
      facilitative aspects of information technologies in clinical practice guideline
      use.

PMID- 15492037
TI  - Processes and problems in the formative evaluation of an interface to the
      Foundational Model of Anatomy knowledge base.
AB  - The Digital Anatomist Foundational Model of Anatomy (FMA) is a large semantic
      network of more than 100,000 terms that refer to the anatomical entities, which
      together with 1.6 million structural relationships symbolically represent the
      physical organization of the human body. Evaluation of such a large knowledge
      base by domain experts is challenging because of the sheer size of the resource
      and the need to evaluate not just classes but also relationships. To meet this
      challenge, the authors have developed a relation-centric query interface, called
      Emily, that is able to query the entire range of classes and relationships in the
      FMA, yet is simple to use by a domain expert. Formative evaluation of this
      interface considered the ability of Emily to formulate queries based on standard
      anatomy examination questions, as well as the processing speed of the query
      engine. Results show that Emily is able to express 90% of the examination
      questions submitted to it and that processing time is generally 1 second or less,
      but can be much longer for complex queries. These results suggest that Emily will
      be a very useful tool, not only for evaluating the FMA, but also for querying and
      evaluating other large semantic networks.

PMID- 15492038
TI  - Modeling electronic discharge summaries as a simple temporal constraint
      satisfaction problem.
AB  - OBJECTIVE: To model the temporal information contained in medical narrative
      reports as a simple temporal constraint satisfaction problem. DESIGN: A
      constraint satisfaction problem is defined by time points and constraints
      (inequalities between points). A time interval comprises a pair of points and a
      constraint. Five complete electronic discharge summaries and paragraphs from 226
      other discharge summaries were studied. Medical events were represented as
      intervals, and assertions about events were represented as constraints. Through a
      consensus process, a set of encoding procedures and a list of issues related to
      encoding were generated. MEASUREMENTS: Instances of temporal disjunction and
      contradiction and distribution of temporal constraints were used. RESULTS: An
      average of 95 medical events (range, 46-151) and 234 temporal assertions (range,
      118-388) were identified per complete discharge summary. Nondefinitional
      assertions were explicit (36%) or implicit (64%) and absolute (17%), qualitative
      (72%), or metric (11%). Implicit assertions were based on domain knowledge and
      assumptions, e.g., the section of the report determined the ordering of events.
      Issues included linking events, intermittence, periodicity, granularity,
      vagueness, ambiguity, uncertainty, and plans. ions such as intermittence were not
      represented explicitly. The temporal network was sparse: Only 0.80% (range, 0.42%
      1.38%) of possible constraints were instantiated. No instances of discontinuous
      temporal disjunction were found in the complete summaries or the 226 paragraphs.
      One instance of temporal contradiction was found (intrareport rate of 0.2 with a
      95% confidence interval of 0.005-1.114). CONCLUSION: A simple temporal constraint
      satisfaction problem appears sufficient to represent most temporal assertions in
      discharge summaries and may be useful for encoding electronic medical records.

PMID- 15492039
TI  - Cardiomyocytes fuse with surrounding noncardiomyocytes and reenter the cell
      cycle.
AB  - The concept of the plasticity or transdifferentiation of adult stem cells has
      been challenged by the phenomenon of cell fusion. In this work, we examined
      whether neonatal cardiomyocytes fuse with various somatic cells including
      endothelial cells, cardiac fibroblasts, bone marrow cells, and endothelial
      progenitor cells spontaneously in vitro. When cardiomyocytes were cocultured with
      endothelial cells or cardiac fibroblasts, they fused and showed phenotypes of
      cardiomyocytes. Furthermore, cardiomyocytes reentered the G2-M phase in the cell
      cycle after fusing with proliferative noncardiomyocytes. Transplanted endothelial
      cells or skeletal muscle-derived cells fused with adult cardiomyocytes in vivo.
      In the cryoinjured heart, there were Ki67-positive cells that expressed both
      cardiac and endothelial lineage marker proteins. These results suggest that
      cardiomyocytes fuse with other cells and enter the cell cycle by maintaining
      their phenotypes.

PMID- 15492041
TI  - Defective function of GABA-containing synaptic vesicles in mice lacking the AP-3B
      clathrin adaptor.
AB  - AP-3 is a member of the adaptor protein (AP) complex family that regulates the
      vesicular transport of cargo proteins in the secretory and endocytic pathways.
      There are two isoforms of AP-3: the ubiquitously expressed AP-3A and the neuron
      specific AP-3B. Although the physiological role of AP-3A has recently been
      elucidated, that of AP-3B remains unsolved. To address this question, we
      generated mice lacking mu3B, a subunit of AP-3B. mu3B-/- mice suffered from
      spontaneous epileptic seizures. Morphological abnormalities were observed at
      synapses in these mice. Biochemical studies demonstrated the impairment of gamma
      aminobutyric acid (GABA) release because of, at least in part, the reduction of
      vesicular GABA transporter in mu3B-/- mice. This facilitated the induction of
      long-term potentiation in the hippocampus and the abnormal propagation of
      neuronal excitability via the temporoammonic pathway. Thus, AP-3B plays a
      critical role in the normal formation and function of a subset of synaptic
      vesicles. This work adds a new aspect to the pathogenesis of epilepsy.

PMID- 15492040
TI  - Distinct molecular forms of beta-catenin are targeted to adhesive or
      transcriptional complexes.
AB  - Beta-catenin plays essential roles in both cell-cell adhesion and Wnt signal
      transduction, but what precisely controls beta-catenin targeting to cadherin
      adhesive complexes, or T-cell factor (TCF)-transcriptional complexes is less well
      understood. We show that during Wnt signaling, a form of beta-catenin is
      generated that binds TCF but not the cadherin cytoplasmic domain. The Wnt
      stimulated, TCF-selective form is monomeric and is regulated by the COOH terminus
      of beta-catenin, which selectively competes cadherin binding through an
      intramolecular fold-back mechanism. Phosphorylation of the cadherin reverses the
      TCF binding selectivity, suggesting another potential layer of regulation. In
      contrast, the main cadherin-binding form of beta-catenin is a beta-catenin-alpha
      catenin dimer, indicating that there is a distinct molecular form of beta-catenin
      that can interact with both the cadherin and alpha-catenin. We propose that
      participation of beta-catenin in adhesion or Wnt signaling is dictated by the
      regulation of distinct molecular forms of beta-catenin with different binding
      properties, rather than simple competition between cadherins and TCFs for a
      single constitutive form. This model explains how cells can control whether beta
      catenin is used independently in cell adhesion and nuclear signaling, or
      competitively so that the two processes are coordinated and interrelated.

PMID- 15492042
TI  - The forces that position a mitotic spindle asymmetrically are tethered until
      after the time of spindle assembly.
AB  - Regulation of the mitotic spindle's position is important for cells to divide
      asymmetrically. Here, we use Caenorhabditis elegans embryos to provide the first
      analysis of the temporal regulation of forces that asymmetrically position a
      mitotic spindle. We find that asymmetric pulling forces, regulated by cortical
      PAR proteins, begin to act as early as prophase and prometaphase, even before the
      spindle forms and shifts to a posterior position. The spindle does not shift
      asymmetrically during these early phases due to a tethering force, mediated by
      astral microtubules that reach the anterior cell cortex. We show that this tether
      is normally released after spindle assembly and independently of anaphase entry.
      Monitoring microtubule dynamics by photobleaching segments of microtubules during
      anaphase revealed that spindle microtubules do not undergo significant poleward
      flux in C. elegans. Together with the known absence of anaphase A, these data
      suggest that the major forces contributing to chromosome separation during
      anaphase originate outside the spindle. We propose that the forces positioning
      the mitotic spindle asymmetrically are tethered until after the time of spindle
      assembly and that these same forces are used later to drive chromosome
      segregation at anaphase.

PMID- 15492043
TI  - Interaction of Brn3a and HIPK2 mediates transcriptional repression of sensory
      neuron survival.
AB  - The Pit1-Oct1-Unc86 domain (POU domain) transcription factor Brn3a controls
      sensory neuron survival by regulating the expression of Trk receptors and members
      of the Bcl-2 family. Loss of Brn3a leads to a dramatic increase in apoptosis and
      severe loss of neurons in sensory ganglia. Although recent evidence suggests that
      Brn3a-mediated transcription can be modified by additional cofactors, the exact
      mechanisms are not known. Here, we report that homeodomain interacting protein
      kinase 2 (HIPK2) is a pro-apoptotic transcriptional cofactor that suppresses
      Brn3a-mediated gene expression. HIPK2 interacts with Brn3a, promotes Brn3a
      binding to DNA, but suppresses Brn3a-dependent transcription of brn3a, trkA, and
      bcl-xL. Overexpression of HIPK2 induces apoptosis in cultured sensory neurons.
      Conversely, targeted deletion of HIPK2 leads to increased expression of Brn3a,
      TrkA, and Bcl-xL, reduced apoptosis and increases in neuron numbers in the
      trigeminal ganglion. Together, these data indicate that HIPK2, through regulation
      of Brn3a-dependent gene expression, is a critical component in the
      transcriptional machinery that controls sensory neuron survival.

PMID- 15492044
TI  - Loss of negative regulation by Numb over Notch is relevant to human breast
      carcinogenesis.
AB  - The biological antagonism between Notch and Numb controls the
      proliferative/differentiative balance in development and homeostasis. Although
      altered Notch signaling has been linked to human diseases, including cancer,
      evidence for a substantial involvement of Notch in human tumors has remained
      elusive. Here, we show that Numb-mediated control on Notch signaling is lost in
      approximately 50% of human mammary carcinomas, due to specific Numb
      ubiquitination and proteasomal degradation. Mechanistically, Numb operates as an
      oncosuppressor, as its ectopic expression in Numb-negative, but not in Numb
      positive, tumor cells inhibits proliferation. Increased Notch signaling is
      observed in Numb-negative tumors, but reverts to basal levels after enforced
      expression of Numb. Conversely, Numb silencing increases Notch signaling in
      normal breast cells and in Numb-positive breast tumors. Finally, growth
      suppression of Numb-negative, but not Numb-positive, breast tumors can be
      achieved by pharmacological inhibition of Notch. Thus, the Numb/Notch biological
      antagonism is relevant to the homeostasis of the normal mammary parenchyma and
      its subversion contributes to human mammary carcinogenesis.

PMID- 15492045
TI  - Differential contribution of Bud6p and Kar9p to microtubule capture and spindle
      orientation in S. cerevisiae.
AB  - In Saccharomyces cerevisiae, spindle orientation is controlled by a temporal and
      spatial program of microtubule (MT)-cortex interactions. This program requires
      Bud6p/Aip3p to direct the old pole to the bud and confine the new pole to the
      mother cell. Bud6p function has been linked to Kar9p, a protein guiding MTs along
      actin cables. Here, we show that Kar9p does not mediate Bud6p functions in
      spindle orientation. Based on live microscopy analysis, kar9Delta cells
      maintained Bud6p-dependent MT capture. Conversely, bud6Delta cells supported
      Kar9p-associated MT delivery to the bud. Moreover, additive phenotypes in
      bud6Delta kar9Delta or bud6Delta dyn1Delta mutants underscored the separate
      contributions of Bud6p, Kar9p, and dynein to spindle positioning. Finally,
      tub2C354S, a mutation decreasing MT dynamics, suppressed a kar9Delta mutation in
      a BUD6-dependent manner. Thus, Kar9p-independent capture at Bud6p sites can
      effect spindle orientation provided MT turnover is reduced. Together, these
      results demonstrate Bud6p function in MT capture at the cell cortex, independent
      of Kar9p-mediated MT delivery along actin cables.

PMID- 15492046
TI  - Outcomes of preventive case management among high-risk elderly in three medical
      groups: a randomized clinical trial.
AB  - Preventive case management was implemented by Sharp Healthcare of San Diego with
      the intention of complementing primary care for geriatric patients enrolled in
      PacifiCare's Secure Horizons Medicare plan. This article presents patient
      outcomes after 12 months of participation. The program featured an annual
      screening questionnaire, appointment monitoring, disease education, and self
      management support. It used a prospective design, tracking randomly assigned
      treatment (n= 1,537) and control patient samples (n = 1,542) for 12 months.
      Outcomes included physical and mental health status; hospital, ER, and nursing
      home use; hospital days and expenditures among persons having an inpatient stay;
      and primary care physician visits. Utilization data were obtained from Sharp
      Healthcare systems and from screening questionnaires. No statistically
      significant main effects were found, but persons with three or more independent
      activity of daily living limitations were about half as likely to have a nursing
      home admission if they were in case management rather than in the control group.

PMID- 15492047
TI  - The validity of subscores for a credentialing test.
AB  - Subscores resulting from the administration of high-stakes tests to candidates
      for credentials in the health professions are desirable for two reasons. First,
      failing candidates want a profile of performance to plan future remedial studies.
      Second, training institutions want a profile of performance for their graduates
      to better evaluate their training. The validity of the interpretation or use of
      subscores depends on a summative judgment based on a combination of reasoning and
      empirical analyses, known as validation. We describe this reasoning process and
      show that with a large credentialing test the validity of any subscore
      interpretation or use can and should be studied systematically. Validity evidence
      should be established to support the interpretation and use of subscores that we
      intend to report. Some principles arise in this study related to the validity of
      subscores, and some procedures are proposed to help testing program personnel
      better validate the use of subscores.

PMID- 15492048
TI  - On assessing the quality of physicians' clinical judgment: the search for outcome
      variables.
AB  - A primary question that must be resolved in the development of tasks to assess
      the quality of physicians' clinical judgment is, "What is the outcome variable?"
      One natural choice would seem to be the correctness of the clinical decision. In
      this article, we use data on the diagnosis of urinary tract infections among
      young girls to illustrate why, in many clinical situations, this is not a useful
      variable. We propose instead a judgment weighted by the relative costs of an
      error. This variable has the disadvantage of requiring expert judgment for
      scoring, but the advantage of measuring the construct of interest.

PMID- 15492049
TI  - Australian eldercare providers: comparing volunteers and temporary staff on work
      environment, interpersonal relationships, and self-efficacy.
AB  - Volunteers (n = 52) and temporary employees (n = 49) at a nonprofit, health care
      program for the elderly in Australia completed measures on community self
      efficacy, sense of community, and caregiver satisfaction and stress. Results
      indicated that both samples of respondents experienced a relatively strong sense
      of common mission to help the elderly, but volunteers, compared to employees,
      reported stronger self-efficacy about making a difference in their community.
      Volunteers, in comparison to temporary (or casual, the preferred term in
      Australia) employees, also reported a stronger sense of reciprocal responsibility
      to help their peers but stronger disharmony among members. Employees compared to
      volunteers reported greater satisfaction as a caregiver. Implications suggest
      marked differences in experiences of eldercare among volunteer and temporary
      employees working with the elderly.

PMID- 15492050
TI  - Telephone survey of hospital staff knowledge of medical device surveillance in a
      Paris hospital.
AB  - Reporting of incidents or near incidents because of medical devices in French
      hospitals relies on procedures following European and national guidelines. The
      authors intend to evaluate hospital staff knowledge on these surveillance
      procedures as a marker of appropriate application. A telephone survey is
      conducted on a sample of Paris University hospital staff (n = 327) using a
      structured questionnaire. Two-hundred sixteen persons completed the
      questionnaire. The response rate was lower among physicians, especially surgeons
      paid on an hourly basis. Rates of correct answers were different according to
      age, seniority, job, and department categories. Physicians and nurses correctly
      answered questions on theoretical knowledge more often than the other job
      categories. However, on questions dealing with actual practice conditions,
      correct answers depended more on age and seniority with a U-shaped distribution
      (minimum rates in intermediate categories of age and seniority).

PMID- 15492051
TI  - Psychometric properties of an instrument designed to measure the educational
      quality of graduate training programs.
AB  - To assess the quality of residency education programs at an academic medical
      center for purposes of enhancing individual graduate medical education programs,
      we asked residents and fellows (N = 419) to evaluate their training programs
      using a Web-based questionnaire (response rate = 70%). Kruskal-Wallis tests,
      factor analysis, correlations, generalizability/decision studies, and mean plots
      were used to examine trainee responses and to assess the questionnaire's
      measurement properties. Exploratory factor analysis indicated that the instrument
      had a three-factor structure that correlated highly with overall program rating.
      Cronbach's alpha exceeded .80 for all factors, and decision studies revealed that
      13 to 23 raters were needed to obtain G-coefficients greater than .70. Mean plots
      showed that the instrument could discriminate within and among training programs
      at the item level and the factor level, which should help target improvements
      across graduate training programs within large institutions.

PMID- 15492053
TI  - Typologies of men who are maritally violent: scientific and clinical
      implications.
AB  - Varying levels and types of husband violence may be conceptualized as typologies
      of maritally violent men. Across studies, batterer subtypes resembling those
      proposed by Holtzworth-Munroe and Stuart (1994) have been identified and
      generally found to differ in predicted ways. Longitudinal data from this study
      suggests that the subgroups continued to differ over three years. Over time,
      however, the placement of individual men into some subtypes was not stable.
      Whether to best conceptualize the heterogeneity among maritally violent men as
      differing subtypes or as variability along dimensions is considered. Clinical
      issues regarding the typology are discussed, including concern that the use of
      absolute cut-off points to identify subtypes is premature and consideration of
      using the typology to predict treatment outcome and to match interventions to
      subtypes. Regarding future research ideas, it is time to consider more immediate,
      situational and dyadic, processes leading to violence perpetration within each
      subtype.

PMID- 15492054
TI  - The place of a typology of men who are "maritally" violent within a nested
      ecological model: a response to Holtzworth-Munroe and Meehan.

PMID- 15492055
TI  - Typology of men who are maritally violent: a discussion of Holtzworth-Munroe and
      Meehan.

PMID- 15492056
TI  - Looking earlier in the life course for the GVA: comment on Holtzworth-Munroe and
      Meehan.

PMID- 15492057
TI  - Can sex offender classification inform typologies of male batterers?: a response
      to Holtzworth-Munroe and Meehan.

PMID- 15492058
TI  - Intimate partner violence and the justice system: an examination of the
      interface.
AB  - Women entering the court system face a challenging experience, in part, because a
      courtroom can be an intimidating and difficult place for any person, and in part
      because women victimized by crimes in which the offender is known to them face
      distinctive difficulties when they seek the court's remedies. The interface is
      also made more challenging for women as the literature offers disparate findings
      as to the efficacy of criminal justice responses and civil remedies. This article
      briefly explores the unique characteristics of intimate partner violence cases
      that influence the interface of these victims with the court system. Areviewis
      provided of research on the criminal justice interventions in cases of intimate
      partner violence; and research on the efficacy of civil protective orders.

PMID- 15492059
TI  - Expanding a community's justice response to sex crimes through advocacy,
      prosecutorial, and public health collaboration: introducing the RESTORE program.
AB  - Problems in criminal justice system response to date-acquaintance rape and
      nonpenetration sexual offenses include (a) they are markers of a sexual offending
      career, yet are viewed as minor; (b) perpetrators are not held accountable in
      ways that reduce reoffense; and (c) criminal justice response disappoints and
      traumatizes victims. To address these problems, a collaboration of victim
      services, prosecutors, legal scholars, and public health professionals are
      implementing and evaluating RESTORE, a victim-driven, community-based restorative
      justice program for selected sex crimes. RESTORE prepares survivors, responsible
      persons (offenders), and both parties' families and friends for face-to-face
      dialogue to identify the harm and develop a redress plan. The program then
      monitors the offender's compliance for 12 months. The article summarizes
      empirical data on problems in criminal justice response, defines restorative
      justice models, and examines outcome. Then the RESTORE program processes and
      goals are described. The article highlights community collaboration in building
      and sustaining this program.

PMID- 15492060
TI  - Helping women understand their risk in situations of intimate partner violence.
AB  - Only approximately one-half of the 456 women who were killed or almost killed by
      a husband, boyfriend, or ex-husband or ex-boyfriend in a recent national study of
      homicide of women accurately perceived their risk of being killed by their
      abusive partner. Women are unlikely to overestimate their risk; however, many
      will underestimate the severity of the situation. From the same study, it was
      found that relatively few of the victims of actual or attempted intimate partner
      femicide were seen by domestic violence advocates during the year before they
      were killed; they were far more likely to be seen in the health care system.
      Implications are drawn as to innovative ways that women who are abused can be
      identified and with skilled assessment of the danger in their relationship helped
      make more informed plans for their safety.

PMID- 15492061
TI  - Separation as a risk factor for victims of intimate partner violence: beyond
      lethality and injury: a response to Campbell.

PMID- 15492062
TI  - Black women and intimate partner violence: new directions for research.
AB  - African American women are at elevated risk for nonfatal and lethal intimate
      partner violence (IPV). Accordingly, the purpose of this article is to review our
      current knowledge, with a focus on the sociodemographic factors that make this
      population particularly vulnerable to abuse. Future research directions include
      using more diverse Black samples, considering how living at the intersection of
      multiple forms of oppression shapes Black women's experience with violence,
      exploring the influence of historical events and oppressive images on
      victimization, and focusing on survivors' resilience and activism.

PMID- 15492063
TI  - The role of substance use in male-to-female physical and sexual violence: a brief
      review and recommendations for future research.
AB  - Literature addressing the relationship between substance use and physical and
      sexual violence against women is reviewed briefly. There is substantial evidence
      of a relationship between men's substance use and perpetration of physical
      violence, some evidence of a relationship between women's substance use and
      experiences of sexual aggression, but weak evidence that men's substance use
      contributes to sexual aggression or that women's substance use contributes to
      their physical victimization. Understanding the mechanisms underlying the
      relationship between substance use and violence relationship will be facilitated
      by narrowing the scope of research questions to identify for whom there is a
      relationship and under what circumstances.

PMID- 15492066
TI  - On uncertainties and errors.

PMID- 15492069
TI  - Economic grand rounds: Financing the care of individuals with serious mental
      illness.

PMID- 15492070
TI  - The emerging crisis in chronic care. 1981.

PMID- 15492071
TI  - Deinstitutionalization: avoiding the disasters of the past. 1979.

PMID- 15492072
TI  - Care of the chronically mentally ill--still a national disgrace. 1979.

PMID- 15492073
TI  - Position statement: a call to action for the chronic mental patient. 1979.

PMID- 15492074
TI  - Pioneering a clear conceptualization of the needs and treatment of persons with
      serious mental illness.

PMID- 15492075
TI  - The need for asylum, not asylums. 1984.

PMID- 15492076
TI  - Asylum within and without asylums.

PMID- 15492077
TI  - The shame of the cities. 1983.

PMID- 15492079
TI  - The fate of the public psychiatric system. 1985.

PMID- 15492080
TI  - Back to the future: funding, integrating, and improving mental health services.

PMID- 15492081
TI  - Action for mental health systems transformation.

PMID- 15492082
TI  - A proposal for future funding of chronic and episodic mental illness. 1986.

PMID- 15492083
TI  - Talbott and financing policy: Reducing fragmentation.

PMID- 15492084
TI  - Lessons learned about the chronic mentally ill since 1955. 1994.

PMID- 15492085
TI  - The need for implementing evidence-based practices.

PMID- 15492087
TI  - 2004 APA Gold Award: Involving the community in the rehabilitation of persons
      with serious mental illness. Skyland Trail, Atlanta, Georgia.

PMID- 15492088
TI  - 2004 APA Gold Award: Using dialectical behavior therapy to help troubled
      adolescents return safely to their families and communities. The Grove Street
      Adolescent Residence of The Bridge of Central Massachusetts, Inc.

PMID- 15492109
TI  - Conceptual divide between adaptive and pathogenetic phenomena in migraine: nausea
      and vomiting.

PMID- 15492113
TI  - Surgery for focal cortical dysplasia.

PMID- 15492114
TI  - Retinoid-induced apoptosis in HL-60 cells is associated with nucleolin down
      regulation and destabilization of Bcl-2 mRNA.
AB  - All-trans retinoic acid (ATRA) induces differentiation of promyelocytic leukemia
      cells, but the mechanisms by which cellular differentiation leads to apoptosis
      are not well understood. Studies were done to address the question whether ATRA
      induced apoptosis is a consequence of destabilization of bcl-2 mRNA and decreased
      cellular levels of the anti-apoptotic protein, bcl-2. ATRA induced
      differentiation of HL-60 cells along the granulocytic pathway within 48 h. The
      half-lives of bcl-2 mRNA in HL-60 cells incubated with ATRA for 48 or 72 h were
      reduced to 39 and 7% of the corresponding untreated control values, respectively.
      Cellular differentiation was accompanied by down-regulation of the cytoplasmic
      levels of nucleolin, a bcl-2 mRNA-stabilizing protein. Binding of a bcl-2 mRNA
      instability element (AU-rich element-1) to nucleolin in S100 extracts from ATRA
      treated cells was decreased to 15% of control within 72 h. The decay of 5'
      capped, polyadenylated bcl-2 mRNA transcripts containing ARE-1 was more rapid in
      S100 extracts from ATRA-treated cells compared with untreated cells. However,
      when recombinant nucleolin was added to extracts of ATRA-treated cells, the rate
      of bcl-2 mRNA decay was similar to the rate in extracts of untreated cells. These
      results provide evidence that ATRA-induced apoptosis is a consequence of cellular
      differentiation, which leads to nucleolin down-regulation and bcl-2 mRNA
      instability.

PMID- 15492115
TI  - Alterations in activating protein 1 composition correlate with phenotypic
      differentiation changes induced by resveratrol in human melanoma.
AB  - Resveratrol has demonstrated preventive and therapeutic activities in a variety
      of tumors. However, the mechanistic basis of its pharmacological effects on human
      melanoma has not been well defined. Our results demonstrated that resveratrol
      significantly inhibited melanoma anchorage-independent growth, and even at high
      doses no distinct apoptosis or cell cycle arrest was observed. It is noteworthy
      that c83-2c (metastatic) and wm3211 (radial growth phase) melanoma cells became
      more dendritic shaped with resveratrol treatment. Major histocompatibility
      complex (MHC) class I antigen and Fas/CD95 constitutive surface expression levels
      were, respectively, increased by 2.7- and 1.6-fold of control in c83-2c cells.
      Resveratrol reduced both activator protein-1 (AP-1) DNA binding and
      transcriptional activities, and supershift assay revealed that AP-1 composition
      was shifted from c-Jun/JunD/Fra-1 to JunD/Fra-1/Fra-2, with markedly increased
      JunD, Fra-1, and Fra-2 protein expression levels in the nucleus. Furthermore, we
      overexpressed Fra-2 in human melanoma cells by using a Fra-2 expression construct
      and both AP-1 transcriptional activity and 12-O-tetradecanoylphorbol-induced
      transcriptional transactivation were reduced significantly, whereas MHC class I
      antigen and Fas/CD95 levels were elevated to 2.0 and 1.8 times of control,
      respectively. Addition of H(2)O(2) (10 muM) partially reversed the inhibition of
      colony proliferation; however, no effects on either MHC class I antigen or Fas
      expression was evident. Although H(2)O(2) restored participation of c-Jun in AP-1
      complexes, H(2)O(2) addition did not affect the induction of Fra-1 and Fra-2 by
      resveratrol nor the morphological changes. We propose that alterations in AP-1
      transcription signaling, mediated by changes in AP-1 dimeric composition and
      reduced intracellular reactive oxygen species levels, substantially contribute to
      the phenotypic changes induced by resveratrol.

PMID- 15492116
TI  - 2,3,7,8-tetrachlorodibenzo-p-dioxin enhances negative selection of T cells in the
      thymus but allows autoreactive T cells to escape deletion and migrate to the
      periphery.
AB  - Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an environmental
      pollutant, has been shown to cause thymic atrophy and apoptosis. However, whether
      TCDD alters the process of T-cell selection in the thymus is not clear. To this
      end, we investigated the effects of TCDD in the context of the HY-T-cell receptor
      (TCR) transgenic (Tg) mouse model. We noted that negatively selecting male HY-TCR
      Tg mice were significantly more sensitive to the thymotoxic effects of TCDD
      relative to positively selecting female HY-TCR Tg mice, including increased
      reduction in cellularity and increased induction of apoptosis. TCDD exposure also
      altered the thymocyte subset composition in HY-TCR Tg male but not female mice.
      In addition, TCDD treatment resulted in increased extracellularly regulated
      kinase phosphorylation and lymphocyte-specific protein tyrosine kinase expression
      in thymocytes of HY-TCR Tg male but not female mice. The increase in proportion
      of CD8+ mature thymocytes noted in HY-TCR Tg male mice was reflected in the
      periphery, with TCDD-exposed HY-TCR Tg male mice having increased numbers of CD8+
      T cells. Finally, we noted that the proliferative response of HY-TCR Tg male T
      cells to HY(self)-Ag was enhanced after exposure to TCDD, whereas that of HY-TCR
      Tg female mice was decreased. Taken together, these data suggest that TCDD alters
      the process of thymic selection, possibly by enhancing negative thymocyte
      selection, whereas at the same time allowing autoreactive T cells to escape
      deletion in the thymus and immigrate to the periphery.

PMID- 15492117
TI  - Interaction between cardiac calsequestrin and drugs with known cardiotoxicity.
AB  - Ca(2+) regulation is coupled to critical signals in eucaryotic cells, and
      calsequestrin is one of the crucial components for this calcium regulation. Our
      previous observations of calsequestrins revealed the existence of three
      thioredoxin-like folds, a basic motif that often provides the platform for small
      molecule binding. Therefore, we have examined the previously reported
      trifluoperazine and other pharmaceuticals that have similar heart-related side
      effects (such as tachycardia; bradycardia; palpitation; changing PR, QRS, QTc
      intervals in electrocardiogram; heart failure) for their binding affinity to
      cardiac calsequestrin (cCSQ) using isothermal titration calorimetry. Our results
      showed that several antipsychotic phenothiazine derivatives, tricyclic
      antidepressants, and anthracycline derivatives bind cCSQ with K(d) in the
      micromolar range. For these compounds that have a significantly low K(d), their
      effect on Ca(2+) binding capacity of cCSQ was checked using equilibrium dialysis
      and atomic absorption spectroscopy, which clearly showed a significant reduction
      in Ca(2+) binding capacity of cCSQ as a result of this interaction. Furthermore,
      8-anilino-1-naphthalene sulfonate (ANS) binding to cCSQ closely resembles ANS
      binding to flavine or nucleotide binding sites. The combination of this
      information with the high abundance of CSQ in SR and the high membrane
      permeability of those drugs led us to the specific hypothesis that there are
      undesirable and damaging interactions between cCSQ and tricyclic antidepressants,
      phenothiazine derivatives, anthracyclines, and many other pharmaceutical
      compounds and to the corollary hypothesis that better understanding of the
      molecular details of cCSQ-drug interactions could lead to modified drug molecules
      with reduced heart-related side effects.

PMID- 15492118
TI  - The composition of the beta-2 adrenergic receptor oligomer affects its membrane
      trafficking after ligand-induced endocytosis.
AB  - The beta-2 adrenergic receptor (B2AR) is well known to form oligomeric complexes
      in vivo, but the functional significance of this process is not fully understood.
      The present results identify an effect of oligomerization of the human B2AR on
      the membrane trafficking of receptors after agonist-induced endocytosis in stably
      transfected human embryonic kidney 293 cells. A sequence present in the
      cytoplasmic tail of the B2AR has been shown previously to be required for
      efficient recycling of internalized receptors. Mutation of this sequence was
      observed to inhibit recycling not only of the receptor containing the mutation
      but also of the coexpressed wild-type B2AR. Coexpression of recycling-defective
      mutant B2ARs also enhanced proteolytic degradation of the wild-type B2AR after
      agonist-induced endocytosis, consistent with trafficking of both receptors to
      lysosomes in an oligomeric complex. Coexpression of the delta opioid receptor
      (DOR) at similar levels produced a much smaller effect on endocytic trafficking
      of the B2AR, even though DOR traverses a similar membrane pathway as recycling
      defective mutant B2ARs. Biochemical studies confirmed that B2AR/B2AR-ala
      homomeric complexes form more readily than DOR/B2AR heteromers in expression
      matched cell clones and support the hypothesis that B2AR/B2AR-ala complexes are
      not disrupted by agonist. These results suggest that a significant fraction of
      B2ARs exists in oligomeric complexes after ligand-induced endocytosis and that
      the composition of the oligomeric complex influences the sorting of endocytosed
      receptors between functionally distinct recycling and degradative membrane
      pathways.

PMID- 15492119
TI  - B1 bradykinin receptor homo-oligomers in receptor cell surface expression and
      signaling: effects of receptor fragments.
AB  - The human B(1) bradykinin receptor is an inducible and constitutively active G
      protein-coupled receptor that is involved in the inflammatory and pain responses
      to injury. Here, we investigated the role of B(1) receptor homo-oligomerization
      in cell surface receptor expression. B(1) receptors tagged with either the FLAG
      or hemagglutinin epitope were monitored immunologically and by radio-ligand
      binding, biotinylation, and phosphoinositide hydrolysis in human embryonic kidney
      293 cells. Selective immunoprecipitation, immunoblotting, and immunoelectron
      microscopy with epitope-specific antibodies together provided evidence for
      constitutively formed cell surface receptor homo-oligomers. Truncation of the
      receptor from the N- and C-terminal ends indicated that the epitope for
      oligomerization seems to be located between Leu(26) on top of transmembrane helix
      1 and Val(71) at the bottom of helix 2. A receptor construct terminating at
      Asp(134) at the bottom of helix 3, B1stop135, was expressed in the cell. It is
      interesting that this construct behaved as a dominant-negative mutant by
      competitively preventing formation of intact B(1) receptor homo-oligomers, and
      redistributing B(1) receptors from the cell surface to a common intracellular
      compartment. In contrast, expression of a construct containing the residues
      downstream of Asp(134), B1del(2-134), was inactive in this regard. Together,
      these results are consistent with a mechanism where constitutive B(1) receptor
      homooligomerization is required for expression of receptors on the cell surface
      and subsequent constitutive receptor signaling. This may be a novel mechanism by
      which the cell regulates the presentation of this constitutively highly active
      receptor at various stages of injury.

PMID- 15492120
TI  - Multiple mechanisms are involved in Ah receptor-mediated cell cycle arrest.
AB  - The liver is the only solid organ that can respond to major tissue loss or damage
      by regeneration to restore liver biomass. The aryl hydrocarbon receptor (AhR)
      agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can disrupt the regenerative
      process, as evidenced by suppression of DNA synthesis in rat primary hepatocytes
      in culture and in vivo liver regeneration after partial hepatectomy. Independent
      observations demonstrated that AhR-mediated G(1) phase cell cycle arrest depends
      on an interaction with the retinoblastoma tumor suppressor protein (pRb), but
      differences exist regarding proposed mechanisms of action. Two distinct models
      have been proposed, one supporting the AhR-pRb interaction functioning in
      corepression of E2F activity and the other favoring an AhR-pRb interaction
      participating in transcriptional coactivation of genes encoding G(1) phase
      regulatory proteins. In the present study, experiments in rat hepatoma cells
      using dominant-negative DNA-binding-defective AhR and Ah receptor nuclear
      translocator (Arnt) mutants provided evidence that TCDD-induced AhR-mediated G(1)
      arrest is only partially regulated by direct AhR transcriptional activity,
      suggesting that both coactivation and corepression are involved. Studies using a
      small interfering RNA to down-regulate Arnt protein expression revealed that TCDD
      induced G(1) arrest is absolutely dependent on the Arnt protein.

PMID- 15492121
TI  - NK cells and trophoblasts: partners in pregnancy.
AB  - In placental mammals, viviparity--the production of living young within the
      mother's body--evolved under the auspices of the immune system. Elements of
      immunity were incorporated, giving pregnancy a mildly inflammatory character.
      Formation of the placenta, the organ that feeds the fetus, involves a cooperation
      between maternal natural killer (NK) cells and fetal trophoblast cells that
      remodels the blood supply. Recent research reveals that this process and human
      reproductive success are influenced by polymorphic HLA-C ligands and their killer
      cell immunoglobulin-like receptors (KIR).

PMID- 15492122
TI  - Plasma cell ontogeny defined by quantitative changes in blimp-1 expression.
AB  - Plasma cells comprise a population of terminally differentiated B cells that are
      dependent on the transcriptional regulator B lymphocyte--induced maturation
      protein 1 (Blimp-1) for their development. We have introduced a gfp reporter into
      the Blimp-1 locus and shown that heterozygous mice express the green fluorescent
      protein in all antibody-secreting cells (ASCs) in vivo and in vitro. In vitro,
      these cells display considerable heterogeneity in surface phenotype,
      immunoglobulin secretion rate, and Blimp-1 expression levels. Importantly,
      analysis of in vivo ASCs induced by immunization reveals a developmental pathway
      in which increasing levels of Blimp-1 expression define developmental stages of
      plasma cell differentiation that have many phenotypic and molecular correlates.
      Thus, maturation from transient plasmablast to long-lived ASCs in bone marrow is
      predicated on quantitative increases in Blimp-1 expression.

PMID- 15492123
TI  - Helicobacter pylori modulates the T helper cell 1/T helper cell 2 balance through
      phase-variable interaction between lipopolysaccharide and DC-SIGN.
AB  - The human gastric pathogen Helicobacter pylori spontaneously switches
      lipopolysaccharide (LPS) Lewis (Le) antigens on and off (phase-variable
      expression), but the biological significance of this is unclear. Here, we report
      that Le+ H. pylori variants are able to bind to the C-type lectin DC-SIGN and
      present on gastric dendritic cells (DCs), and demonstrate that this interaction
      blocks T helper cell (Th)1 development. In contrast, Le- variants escape binding
      to DCs and induce a strong Th1 cell response. In addition, in gastric biopsies
      challenged ex vivo with Le+ variants that bind DC-SIGN, interleukin 6 production
      is decreased, indicative of increased immune suppression. Our data indicate a
      role for LPS phase variation and Le antigen expression by H. pylori in
      suppressing immune responses through DC-SIGN.

PMID- 15492124
TI  - Gene dosage--limiting role of Aire in thymic expression, clonal deletion, and
      organ-specific autoimmunity.
AB  - Inactivation of the autoimmune regulator (Aire) gene causes a rare recessive
      disorder, autoimmune polyendocrine syndrome 1 (APS1), but it is not known if Aire
      dependent tolerance mechanisms are susceptible to the quantitative genetic
      changes thought to underlie more common autoimmune diseases. In mice with a
      targeted mutation, complete loss of Aire abolished expression of an insulin
      promoter transgene in thymic epithelium, but had no effect in pancreatic islets
      or the testes. Loss of one copy of Aire diminished thymic expression of the
      endogenous insulin gene and the transgene, resulting in a 300% increase in islet
      reactive CD4 T cells escaping thymic deletion in T cell receptor transgenic mice,
      and dramatically increased progression to diabetes. Thymic deletion induced by
      antigen under control of the thyroglobulin promoter was abolished in Aire
      homozygotes and less efficient in heterozygotes, providing an explanation for
      thyroid autoimmunity in APS1. In contrast, Aire deficiency had no effect on
      thymic deletion to antigen controlled by a systemic H-2K promoter. The
      sensitivity of Aire-dependent thymic deletion to small reductions in function
      makes this pathway a prime candidate for more subtle autoimmune quantitative
      trait loci, and suggests that methods to increase Aire activity would be a potent
      strategy to lower the incidence of organ-specific autoimmunity.

PMID- 15492125
TI  - Remodeling of axonal connections contributes to recovery in an animal model of
      multiple sclerosis.
AB  - In multiple sclerosis (MS), inflammation in the central nervous system (CNS)
      leads to damage of axons and myelin. Early during the clinical course, patients
      can compensate this damage, but little is known about the changes that underlie
      this improvement of neurological function. To study axonal changes that may
      contribute to recovery, we made use of an animal model of MS, which allows us to
      target inflammatory lesions to the corticospinal tract (CST), a major descending
      motor pathway. We demonstrate that axons remodel at multiple levels in response
      to a single neuroinflammatory lesion as follows: (a) surrounding the lesion,
      local interneurons show regenerative sprouting; (b) above the lesion, descending
      CST axons extend new collaterals that establish a "detour" circuit to the lumbar
      target area, whereas below the lesion, spared CST axons increase their terminal
      branching; and (c) in the motor cortex, the distribution of projection neurons is
      remodeled, and new neurons are recruited to the cortical motor pool. Behavioral
      tests directly show the importance of these changes for recovery. This paper
      provides evidence for a highly plastic response of the motor system to a single
      neuroinflammatory lesion. This framework will help to understand the endogenous
      repair capacity of the CNS and to develop therapeutic strategies to support it.

PMID- 15492126
TI  - Central tolerance to tissue-specific antigens mediated by direct and indirect
      antigen presentation.
AB  - Intrathymic expression of tissue-specific antigens (TSAs) by medullary thymic
      epithelial cells (Mtecs) leads to deletion of autoreactive T cells. However,
      because Mtecs are known to be poor antigen-presenting cells (APCs) for tolerance
      to ubiquitous antigens, and very few Mtecs express a given TSA, it was unclear if
      central tolerance to TSA was induced directly by Mtec antigen presentation or
      indirectly by thymic bone marrow (BM)-derived cells via cross-presentation. We
      show that professional BM-derived APCs acquire TSAs from Mtecs and delete
      autoreactive CD8 and CD4 T cells. Although direct antigen presentation by Mtecs
      did not delete the CD4 T cell population tested in this study, Mtec presentation
      efficiently deleted both monoclonal and polyclonal populations of CD8 T cells.
      For developing CD8 T cells, deletion by BM-derived APC and by Mtec presentation
      occurred abruptly at the transitional, CD4high CD8low TCRintermediate stage,
      presumably as the cells transit from the cortex to the medulla. These studies
      reveal a cooperative relationship between Mtecs and BM-derived cells in thymic
      elimination of autoreactive T cells. Although Mtecs synthesize TSAs and delete a
      subset of autoreactive T cells, BM-derived cells extend the range of clonal
      deletion by cross-presenting antigen captured from Mtecs.

PMID- 15492128
TI  - Birth weight is inversely correlated to adult systolic blood pressure and pulse
      pressure in type 1 diabetes.
AB  - In the general population, there is an inverse relationship between birth weight
      and adult systolic blood pressure. Because blood pressure in diabetic patients at
      least in part seems to be regulated by different mechanisms than in nondiabetic
      subjects, it is not known whether a similar correlation exists in diabetic
      individuals. Therefore, we obtained data on birth weight from original birth
      certificates in 1543 type 1 diabetic patients. Blood pressure was measured
      auscultatorily on a single occasion. In the 1225 patients born at term (after 37
      weeks of gestation), the age- and sex-adjusted regression coefficients between
      systolic blood pressure and birth weight was -1.90 mm Hg/kg (95% confidence
      interval [CI], -3.71 to -0.09). The finding remained unchanged after adjustment
      for body mass index, current smoking, duration of diabetes, social class,
      antihypertensive therapy, glomerular filtration rate, glycemic control, and
      elevated albuminuria. The regression coefficient between birth weight and pulse
      pressure was of a similar magnitude. The age-adjusted regression coefficient
      between systolic blood pressure and birth weight seemed stronger in females (
      3.34 mm Hg/kg; 95% CI, -6.06 to -0.62) than in males (-0.42 mm Hg/kg; 95% CI, 
      2.80 to 1.95), although this difference was not statistically significant. As a
      new finding, we report an inverse relationship between weight at birth and
      systolic blood pressure and pulse pressure in adult type 1 diabetic patients.
      Given the deleterious effects of elevated arterial blood pressure in diabetes,
      the impact of intrauterine growth retardation on the development of end-organ
      damage needs to be clarified.

PMID- 15492127
TI  - CTLA-4-Ig activates forkhead transcription factors and protects dendritic cells
      from oxidative stress in nonobese diabetic mice.
AB  - Prediabetes and diabetes in nonobese diabetic (NOD) mice have been targeted by a
      variety of immunotherapies, including the use of a soluble form of cytotoxic T
      lymphocyte antigen 4 (CTLA-4) and interferon (IFN)-gamma. The cytokine, however,
      fails to activate tolerogenic properties in dendritic cells (DCs) from highly
      susceptible female mice early in prediabetes. The defect is characterized by
      impaired induction of immunosuppressive tryptophan catabolism, is related to
      transient blockade of the signal transducer and activator of transcription
      (STAT)1 pathway of intracellular signaling by IFN-gamma, and is caused by
      peroxynitrite production. Here, we show that soluble CTLA-4 imparts suppressive
      properties to DCs from early prediabetic NOD female mice through mechanisms that
      rely on autocrine signaling by IFN-gamma. Although phosphorylation of STAT1 in
      response to IFN-gamma is compromised in those mice, CTLA-4 obviates the defect.
      IFN-gamma-driven expression of tryptophan catabolism by CTLA-4-immunoglobulin is
      made possible through the concomitant activation of the Forkhead Box class O
      (FOXO) transcription factor FOXO3a, induction of the superoxide dismutase gene,
      and prevention of peroxynitrite formation.

PMID- 15492129
TI  - Platelet-derived growth factor induces tissue factor expression in vascular
      smooth muscle cells via activation of Egr-1.
AB  - Activation of vascular smooth muscle cells (SMCs) by platelet-derived growth
      factor (PDGF) is a seminal event in the initiation and progression of the
      atherosclerotic lesion and may contribute to atherosclerotic plaque instability
      with plaque rupture and thrombus formation. Tissue factor (TF), a prothrombotic
      molecule expressed by various cell types within atherosclerotic plaques, is
      thought to play a major role in thrombus formation after plaque rupture. This
      study examined intracellular signaling pathways leading to TF expression and Egr
      1 activation, a key element in tissue factor transcription, by PDGF-BB in rat
      SMCs. PDGF-BB induced TF mRNA and protein expression in a time-dependent manner.
      Early growth response factor-1 (Egr-1) binding activity was also induced by PDGF
      BB, as well as phosphorylation of extracellular signal-regulated kinase. PDGF-BB
      induced Egr-1 activation was suppressed by inhibitors of 2 upstream activators of
      Egr-1, extracellular signal-regulated kinase (ERK) and Src family kinases,
      whereas antioxidants, phosphatidylinositol 3-phosphate kinase, and p38 MAPK
      inhibitors had no effect. PDGF-BB-stimulated expression of the transcriptional co
      repressor NAB2 was time-dependent. Furthermore, transient transfections of SMCs
      with wild-type and mutated TF promoter constructs showed that the Egr-1 binding
      region is an important transcriptional regulator of PDGF-BB-induced TF
      expression. Taken together, the results suggest that PDGF-BB induces TF
      expression and activity in SMC by a Src family kinases/ERK/Egr-1 signaling
      pathway and may therefore contribute to thrombus formation in advanced
      atherosclerosis and restenosis.

PMID- 15492130
TI  - Upregulation of vascular arginase in hypertension decreases nitric oxide-mediated
      dilation of coronary arterioles.
AB  - One characteristic of hypertension is a decreased endothelium-dependent nitric
      oxide (NO)-mediated vasodilation; however, the underlying mechanism is complex.
      In endothelial cells (ECs), L-arginine is the substrate for both NO synthase
      (NOS) and arginase. Because arginase has recently been shown to modulate NO
      mediated dilation of coronary arterioles by reducing l-arginine availability, we
      hypothesized that upregulation of vascular arginase in hypertension contributes
      to decreased NO-mediated vasodilation. To test this hypothesis, hypertension
      (mean arterial blood pressure >150 mm Hg) was maintained for 8 weeks in pigs by
      aortic coarctation. Coronary arterioles from normotensive (NT) and hypertensive
      (HT) pigs were isolated and pressurized for in vitro study. NT vessels dilated
      dose-dependently to adenosine (partially mediated by endothelial release of NO)
      and sodium nitroprusside (endothelium-independent vasodilator). Conversely, HT
      vessels exhibited reduced dilation to adenosine but dilated normally to sodium
      nitroprusside. Adenosine-stimulated NO release was increased approximately 3-fold
      in NT vessels but was reduced in HT vessels. Moreover, arginase activity was 2
      fold higher in HT vessels. Inhibition of arginase activity by N(omega)-hydroxy
      nor-l-arginine or incubation with l-arginine partially restored NO release and
      dilation to adenosine in HT vessels. Immunohistochemistry showed that arginase
      expression was increased but NOS expression was decreased in arteriolar ECs of HT
      vessels. These results suggest that NO-mediated dilation of coronary arterioles
      is inhibited in hypertension by an increase in arginase activity in EC, which
      limits l-arginine availability to NOS for NO production. The inability of
      arginase blockade or l-arginine supplementation to completely restore
      vasodilation may be related to downregulation of endothelial NOS expression.

PMID- 15492132
TI  - Alcohol-associated hypertension: when one drinks makes a difference.

PMID- 15492131
TI  - Inflammation, abdominal obesity, and smoking as predictors of hypertension.
AB  - Development of hypertension has been linked to chronic low-grade inflammation.
      However, it is not known whether this connection is mediated by features of the
      metabolic syndrome or smoking, or their changes, which themselves have been
      linked to inflammation. We studied the predictive value of highly sensitive C
      reactive protein (hs-CRP), smoking, and abdominal obesity to the development of
      hypertension in an 11-year follow-up of a population-based study cohort
      comprising 379 middle-aged normotensive men. During the follow-up, 124 men (33%)
      developed hypertension. Men with hs-CRP > or =3.0 mg/L were 2.8x (95% confidence
      interval, 1.2 to 6.6) more likely to develop hypertension than with hs-CRP <1.0
      mg/L even after adjustment for features of the metabolic syndrome, lifestyle
      factors, and their changes. Cigarette smoking was also associated with
      development of hypertension independently of inflammation and other confounders.
      Waist girth increased more in men who quit smoking than in other men. An increase
      in waist girth during follow-up strongly predicted incident hypertension. The
      decrease in smoking was not associated with a lower risk of hypertension in age
      adjusted analyses. Hypertension is preceded by low-grade chronic inflammation in
      middle-aged white men independently of smoking or features of the metabolic
      syndrome. Furthermore, smoking may be a risk factor for hypertension. Although
      stopping smoking is beneficial with respect to health outcomes, the subsequent
      increase in weight and waist girth associated with smoking cessation may offset
      the decrease in the risk of hypertension that one may otherwise expect.

PMID- 15492133
TI  - Neutral endopeptidase inhibition augments vascular actions of bradykinin in
      patients treated with angiotensin-converting enzyme inhibition.
AB  - Angiotensin-converting enzyme and neutral endopeptidase (EC 3.4.24.11;
      neprilysin) are metallopeptidases present on the endothelium that metabolize
      bradykinin. Inhibitors of angiotensin-converting enzyme potentiate bradykinin
      mediated vasodilatation and endothelial tissue plasminogen activator release.
      Combined angiotensin-converting enzyme and neutral endopeptidase inhibition may
      have additional beneficial cardiovascular effects mediated through bradykinin
      potentiation. We investigated the effects of local neutral endopeptidase
      inhibition on the vascular actions of bradykinin in heart failure patients
      maintained on chronic angiotensin-converting enzyme inhibition. Ten patients
      received intrabrachial infusion of thiorphan (30 nmol/min), a neutral
      endopeptidase inhibitor, in a randomized double-blind placebo-controlled
      crossover trial. Thiorphan was coinfused with Lys-des-Arg9-bradykinin (1 to 10
      nmol/min), bradykinin (30 to 300 pmol/min), atrial natriuretic peptide (10 to 100
      pmol/min), and sodium nitroprusside (2 to 8 mug/min). Bradykinin, atrial
      natriuretic peptide, and sodium nitroprusside caused dose-dependent
      vasodilatation (peak blood flow 14.4+/-2.2, 3.6+/-0.6, and 8.6+/-1.3 mL per 100
      mL/min, respectively; P<0.0001). Bradykinin caused dose-dependent increases in
      tissue plasminogen activator antigen and activity (peak concentration 31.8+/-3.4
      ng/mL and 21.9+/-7.6 IU/mL, respectively; P<0.001) and estimated antigen and
      activity release (peak release 152+/-46 ng per 100 mL/min and 154+/-22 IU/100
      mL/min, respectively; P<0.005). Compared with placebo, thiorphan augmented
      bradykinin-mediated vasodilatation (1.4-fold; P<0.0001) and net tissue
      plasminogen activator release (1.5-fold; P<0.005). Neutral endopeptidase
      contributes to bradykinin metabolism in heart failure patients maintained on
      angiotensin-converting enzyme inhibitor therapy. Our findings may explain some of
      the clinical effects of combined angiotensin-converting enzyme and neutral
      endopeptidase inhibition, including the greater vasodepressor effect observed
      with combined therapy when compared with angiotensin-converting enzyme inhibition
      alone.

PMID- 15492135
TI  - Changes in wave reflection with advancing age in normal subjects.

PMID- 15492137
TI  - Roles of the renal kallikrein-kinin system in salt-sensitive hypertension.

PMID- 15492138
TI  - Structure-based discovery of a novel angiotensin-converting enzyme 2 inhibitor.
AB  - Angiotensin-converting enzyme 2 (ACE2) is considered an important therapeutic
      target for controlling cardiovascular diseases and severe acute respiratory
      syndrome (SARS) outbreaks. Recently solved high-resolution crystal structures of
      the apo-bound and inhibitor-bound forms of ACE2 have provided the basis for a
      novel molecular docking approach in an attempt to identify ACE2 inhibitors and
      compounds that block SARS coronavirus spike protein-mediated cell fusion. In this
      study, approximately 140 000 small molecules were screened by in silico molecular
      docking. In this structure-activity relation study, the molecules with the
      highest predicted binding scores were identified and assayed for ACE2 enzymatic
      inhibitory activity and for their ability to inhibit SARS coronavirus spike
      protein-mediated cell fusion. This approach identified N-(2-aminoethyl)-1
      aziridine-ethanamine as a novel ACE2 inhibitor that also is effective in blocking
      the SARS coronavirus spike protein-mediated cell fusion. Thus, the molecular
      docking approach resulting in the inhibitory capacity of N-(2-aminoethyl)-1
      aziridine-ethanamine provides an attractive small molecule lead compound on which
      the development of more effective therapeutic agents could be developed to
      modulate hypertension and for controlling SARS infections.

PMID- 15492139
TI  - Field Memorial Community Hospital, Department of Surgery.

PMID- 15492140
TI  - Prospective evaluation of positron emission tomography in the preoperative
      staging of esophageal carcinoma.
AB  - HYPOTHESIS: Positron emission tomography (PET) is a useful tool in the selection
      of patients with esophageal cancer who may not benefit from esophageal resection.
      DESIGN: Case series. SETTING: Tertiary care hospital. PATIENTS: Eighty-one
      patients with newly diagnosed esophageal cancer who underwent PET and computer
      tomography (CT) of the chest and abdomen (and of the neck in 45 patients) within
      45 days were included. MAIN OUTCOME MEASURES: We calculated the sensitivity and
      specificity in detecting metastatic sites on the basis of 31 histologically
      verified lesions. In addition to results obtained on CT, the information provided
      by PET was evaluated with a view to the choice of management strategies. RESULTS:
      The PET findings had a higher specificity (89% vs 11%) but a lower sensitivity
      (38% vs 63%) than CT findings in the detection of metastatic sites. The CT
      results showed greater agreement with histopathological findings than did PET
      results. In 8 patients (10%), PET detected distant metastases that were not
      identified with CT. In 4 patients (5%), PET detected bone metastases only, but in
      all of these patients metastases in other locations were detected by CT. Although
      PET led to upstaging (M1) in 2 patients (2%), it did not enable the exclusion of
      esophageal resection. CONCLUSIONS: Preoperative PET was not characterized by
      greater accuracy in the detection of metastatic sites previously identified by
      CT. Therefore, PET did not lead to a change in the indication for esophagectomy.
      An increase in the sensitivity and the combined use of CT and PET may lead to new
      indications for this staging procedure.

PMID- 15492141
TI  - Bilioenteric reconstruction for small bile ducts without mucosa-to-mucosa
      alignment: long-term results.
AB  - HYPOTHESIS: Biliary reconstruction of the small bile duct is difficult, and
      bilioenteric reconstruction without mucosa-to-mucosa alignment would be a simple
      and useful maneuver in this situation; however, the long-term results of this
      surgical technique remain to be evaluated. OBJECTIVE: To evaluate the usefulness
      of bilioenteric reconstruction without mucosa-to-mucosa alignment from the
      standpoint of the long-term results. DESIGN: Retrospective review. SETTING:
      University hospital. PATIENTS: Bilioenteric reconstruction without mucosa-to
      mucosa alignment was performed in 17 patients at our institution. Six patients
      had malignancy, and 11 were liver transplant recipients from a living donor. MAIN
      OUTCOME MEASURES: Clinical records, blood chemistry data, and findings from
      dynamic computed tomography. RESULTS: Among the 17 patients, 4 died of recurrent
      malignant disease, and 3 died of thrombosis, brain hemorrhage, and pneumonia,
      respectively. During the follow-up (median, 41.2 months) of the remaining 10
      patients, cholangitis occurred in 2 (1 episode in each), and anastomotic leakage
      from the hepaticojejunostomy performed by the standard method for other thicker
      ducts developed in 1. There were no other anastomosis-related complications.
      Dynamic computed tomography performed 2.4 to 62.7 months (median, 34.4 months)
      after the operation showed no bile duct dilatation in any of the 10 cases.
      CONCLUSIONS: Long-term patency of the small bile ducts after bilioenteric
      reconstruction without mucosa-to-mucosa alignment was demonstrated. Thus, this
      technique is useful for the reconstruction of small bile ducts, especially in
      patients with poor liver function in whom even minimal additional reduction in
      the volume of functioning liver due to occlusion of a small bile duct would be
      acceptable.

PMID- 15492142
TI  - Circulating messenger RNA of alpha-fetoprotein: a possible risk factor of
      recurrence after resection of hepatocellular carcinoma.
AB  - HYPOTHESIS: Isolated tumor cells may be associated with micrometastasis.
      Circulating alpha-fetoprotein messenger RNA (AFP mRNA) in patients with
      hepatocellular carcinoma (HCC) has been considered to represent isolated tumor
      cells. We propose that circulating AFP mRNA may have prognostic value after
      curative resection of HCC. DESIGN: A prospective cohort study. SETTING: Referral
      center. PATIENTS: Eighty-one consecutive patients who underwent curative
      resection of HCC. MEASUREMENTS: A nested reverse-transcriptase polymerase chain
      reaction (RT-PCR) assay for circulating AFP mRNA before and again 12 weeks after
      surgery in 81 patients and in a control group. Clinicopathological variables and
      postoperative course (recurrence and recurrence-free survival) were examined for
      correlation with the levels of circulating AFP mRNA. RESULTS: Of the 81 patients,
      22 (27.2%) and 19 (23.4%) had AFP mRNA detected preoperatively and
      postoperatively, respectively. The recurrence-free survival at 1, 2, and 3 years
      after resection was significantly shorter in the latter patients (52.6%, 15.6%,
      and 0%, respectively; P<.001) but not in the former (81.8%, 54.5%, and 29.2%; P =
      .28). In univariate analysis, a significantly higher recurrence rate was found in
      patients with liver cirrhosis (P = .03), Edmondson-Steiner differentiation grade
      III or IV (P<.001), incomplete or absent capsule (P = .001), vascular invasion
      (P<.001), daughter nodules (P = .003), or a positivity for postoperative
      circulating AFP mRNA (P<.001). Postoperative positivity for circulating AFP mRNA
      remained a significant risk factor (P = .002; hazard ratio 3.13; 95% confidence
      interval, 1.52-6.47) in the multivariate analysis. CONCLUSION: The detection of
      circulating AFP mRNA 12 weeks postoperatively is associated with an increased and
      earlier risk of HCC recurrence.

PMID- 15492143
TI  - Techniques for hepatectomies without blood transfusion, focusing on
      interpretation of postoperative anemia.
AB  - HYPOTHESIS: Transient postoperative anemia is partially a physiologic phenomenon,
      and variations in blood transfusion rates after liver resection in different
      series in part are due to different interpretations of postoperative anemia.
      Based on the hypothesis that transient postoperative anemia is partially a
      physiologic phenomenon, we analyzed serum hemoglobin and hematocrit values in
      patients who underwent liver resection without blood transfusion to check
      fluctuations. DESIGN: Prospective cohort study. SETTING: Community hospital.
      PATIENTS: Forty-six consecutive patients with primary and metastatic liver
      tumors. INTERVENTIONS: Surgical treatment consisting of dissection technique
      performed under intermittent warm ischemia, using intraoperative ultrasonography,
      and without blood transfusion. MAIN OUTCOME MEASURES: Hematocrit and hemoglobin
      concentrations in serum sampled preoperatively and on the first, third, fifth,
      and seventh postoperative days. RESULTS: No postoperative mortality and major
      morbidity were observed. No patient received a blood transfusion. The hematocrit
      and hemoglobin concentrations in serum were significantly lower on the third
      postoperative day than on the first, fifth, and seventh postoperative days;
      differences among the first, fifth, and seventh postoperative days were not
      significant. CONCLUSIONS: The fluctuations of hemoglobin and hematocrit levels
      after liver resection showed a steady and significant decrease until the third
      postoperative day and then an increase. Therefore, a decrease in the hemoglobin
      and hematocrit levels between first and fifth postoperative days without evidence
      of active bleeding from drain discharge or any other possible source of bleeding
      does not justify blood administration.

PMID- 15492144
TI  - Outcome and prognostic factors in head injuries with an admission Glasgow Coma
      Scale score of 3.
AB  - HYPOTHESIS: To identify significant risk factors associated with mortality in
      patients with a Glasgow Coma Scale score of 3. DESIGN: Trauma registry study.
      SETTING: Level I urban trauma center. PATIENTS: A total of 760 patients with head
      injury with an admission Glasgow Coma Scale score of 3. Analysis was performed in
      all patients and in only patients who reached the hospital alive and had no major
      extracranial injuries (exclusion of patients with a chest or abdominal
      Abbreviated Injury Score [AIS] >3). MAIN OUTCOME MEASURES: Stepwise logistic
      regression analysis was used to identify independent risk factors associated with
      mortality. RESULTS: Blunt trauma accounted for 477 (63%) and penetrating trauma
      for 283 (37%) of the 760 head injuries. Penetrating trauma was significantly more
      likely to be associated with a lack of vital signs on admission (15% vs 9%; P =
      .03). Overall mortality was 76% (94% for penetrating injuries and 65% for blunt
      injuries; P<.001). Overall, 79% of patients had a head AIS of 4 or greater.
      Mortality in the subgroup was 64% (320/497) and was significantly higher in
      penetrating vs blunt trauma (89% vs 52%; P<.001). Penetrating trauma, high head
      AIS, hypotension on admission, and age older than 55 years were independent
      significant risk factors associated with mortality. Only 10% of the 177 survivors
      had good functional outcome at hospital discharge. Eighty-six patients (17% of
      those with vital signs on admission) became organ donors. CONCLUSIONS: Patients
      with head injury with an admission Glasgow Coma Scale score of 3 have a poor
      prognosis. Mechanism of injury, head AIS, hypotension on admission, and age play
      a critical role in outcome. These patients are an important source of organ
      donation and should be evaluated and resuscitated aggressively.

PMID- 15492145
TI  - Ischemic arterial complications after liver transplantation in the adult:
      multivariate analysis of risk factors.
AB  - HYPOTHESIS: To minimize the incidence of ischemic arterial complications, risk
      factors should be clearly identified. Knowledge of the predisposing factors for
      such complications would make possible the institution of strict surveillance
      protocols that could ensure early detection of complications and so prevent the
      progression of ischemic damage to graft failure. DESIGN: Retrospective univariate
      and multivariate analysis. SETTING: University hospital. PATIENTS: Six hundred
      fifty-three adults who underwent 747 orthotopic liver transplantations. MAIN
      OUTCOME MEASURES: We used univariate and multivariate analyses to retrospectively
      assess the role of possible risk factors for early and late HA thrombosis (HAT)
      and stenosis (HAS), including etiology of liver disease, donor and recipient sex
      and age (aged < or =60 vs >60 years), cause of donor death, preservation
      solution, cold ischemic time, previous orthotopic liver transplantation, HA back
      table reconstruction, direct arterial anastomosis vs interpositional conduit,
      experience of the surgeon, intraoperative transfusion requirements, acute
      rejection, and cytomegalovirus infection. RESULTS: We observed 58 ischemic
      complications, including 26 early HAT, 13 late HAT, and 19 HAS. Independent
      predictors of early HAT were donor age greater than 60 years and bench
      reconstruction of anatomical variants of the HA; of late HAT, arterial
      anastomosis fashioned using an interpositional graft of donor iliac artery (iliac
      conduit) and donors who died of cerebrovascular accident; and of HAS, previous
      orthotopic liver transplantation and cytomegalovirus infection. CONCLUSIONS:
      Predisposing factors for HAT mostly stem from donor and graft features. Use of
      iliac conduits should be limited, particularly when using old donors. Frequent
      screening of the arterial flow to the graft with Doppler ultrasonography is
      advisable in patients at risk.

PMID- 15492146
TI  - Gamma-guided diagnostic peritoneal lavage for detection of bowel perforation.
AB  - HYPOTHESIS: Bowel perforation can be diagnosed by detection of orally
      administered technetium Tc 99m sulfur colloid ((99m)Tc SC) in diagnostic
      peritoneal lavage (DPL) fluid using a handheld gamma-detection probe. DESIGN: A
      canine intestinal-injury model was used to test the hypothesis. The (99m)Tc SC
      (55.5 MBq) was administered in 500 mL of saline via a nasogastric tube. A DPL
      with 500 mL of saline was performed at 60, 90, and 120 minutes after
      administration of (99m)Tc SC. The radioactivity in the DPL effluent was measured
      using a handheld gamma probe. A DPL effluent count that was 3 SDs above the
      background count was considered a positive test result. Twenty animals with
      perforation and 5 without perforation (negative control) were studied. RESULTS:
      There were no false-positive gamma-DPL test results. Sensitivity improved by time
      up to 90 minutes. The lowest positive count in the DPL effluent measured by the
      gamma probe corresponded to 0.2% of the administered activity. No radioactivity
      was detected in blood and urine samples or liver and spleen specimens. The
      sensitivity, specificity, accuracy, positive predictive values, and negative
      predictive values at 90 minutes were 95%, 100%, 96%, 100%, and 83%, respectively.
      CONCLUSIONS: gamma-Guided DPL is a highly sensitive and 100% specific test in the
      detection of small-bowel perforation. Clinical studies are warranted to determine
      the patient-specific factors affecting diagnostic accuracy.

PMID- 15492147
TI  - Men with breast cancer have better disease-specific survival than women.
AB  - HYPOTHESIS: Male breast cancer patients have better disease-specific survival
      than carefully matched female breast cancer patients. DESIGN: Retrospective
      study. SETTING: University hospital. PATIENTS AND METHODS: Each man in the breast
      cancer database at Columbia-Presbyterian Medical Center (New York, NY) between
      the years 1980 and 1998 was matched with a woman. Matching was done based on age
      and date of diagnosis, stage, and primary histologic findings. MAIN OUTCOME
      MEASURES: The overall survivals and disease-specific survivals of the male breast
      cancer group and female breast cancer group were compared. RESULTS: Fifty-three
      male patients were matched with an equal number of female breast cancer patients.
      The Kaplan-Meier curves demonstrated that there was no significant difference in
      overall survival. The 5- and 10-year survivals for women were 0.77 and 0.51, and
      for men 0.77 and 0.56. When the Kaplan-Meier curves for breast cancer-specific
      survival were compared, however, there was a significant difference in the 5- and
      10-year survivals (P = .05, log-rank test). For women, the 5- and 10-year disease
      specific survival was 0.81 and 0.7, respectively, while for men it was 0.9 and
      0.9, respectively. In a Cox regression analysis for time to death from breast
      cancer, stage was the only predictor of death that approached significance (P =
      .06). CONCLUSIONS: While the overall survivals were equivalent, male breast
      cancer patients had significantly better disease-specific survivals compared with
      their female counterparts. Male patients were 4 times more likely to die of other
      causes than their breast cancer.

PMID- 15492148
TI  - Nontraumatic perforation of the bile duct in adults.
AB  - HYPOTHESIS: Nontraumatic perforation of the bile duct in adults is rare, and the
      management of this condition should resolve the primary pathologic lesion.
      DESIGN: Retrospective analysis of 11 patients who were diagnosed as having
      nontraumatic perforation of the bile duct. SETTING: A public university medical
      center and a private university medical center. PATIENTS: Five men and 6 women
      (median age, 64 years) with nontraumatic perforation of the bile duct were
      treated between September 1993 and May 2003. INTERVENTIONS: Two patients with
      common bile duct (CBD) stones, who were initially diagnosed as having mediastinal
      abscess and subcapsular biloma, respectively, were treated by nonoperative
      management, ie, endoscopic sphincterotomy and percutaneous abscess drainage. The
      remaining 9 patients were treated surgically, which included an exploration of
      the CBD, placement of a T tube, and a liver resection. MAIN OUTCOME MEASURES:
      Initial manifestation, primary disease, perforation site, management, surgical
      morbidity, and mortality. RESULTS: All patients had acute abdominal pain, which
      was caused by intraabdominal abscess in 7 patients, diffuse bile peritonitis in
      3, and subcapsular biloma in 1. Their primary diseases were CBD stones in 7
      patients, intrahepatic duct stone in 2, a choledochal cyst in 1, and phytobezoar
      with food stuff in the CBD in 1. Perforations occurred at the left intrahepatic
      duct in 9 patients, the CBD in 1, and the cyst wall in 1. All patients recovered,
      except 1 patient who expired owing to multiorgan failure because the operation
      could not be performed in time. CONCLUSIONS: Nontraumatic perforation of the bile
      duct should be suspected if perihepatic abscess or peritonitis is combined with
      biliary stone disease. The management of nontraumatic perforation of the bile
      duct should include the eradication of the primary pathologic lesion and the
      control of abscess or peritonitis.

PMID- 15492149
TI  - Effects of obesity surgery on the metabolic syndrome.
AB  - HYPOTHESIS: Individuals with the metabolic syndrome (MS), a clustering of risk
      factors (high levels of triglycerides and serum glucose, low level of high
      density-lipoprotein cholesterol, high blood pressure, abdominal obesity) defined
      by the Third Report of the National Cholesterol Education Program Expert Panel of
      Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult
      Treatment Panel III) (ATPIII), are at high risk of developing coronary heart
      disease and type 2 diabetes mellitus and may benefit from surgically induced
      weight loss. DESIGN: Prospectively controlled clinical study. SETTING: A tertiary
      referral center. PATIENTS: From December 1, 1999, to March 31, 2002, 645
      consecutive morbidly obese patients were enrolled in a surgically supervised
      weight loss program, and the efficacy of weight loss 1 year after surgery was
      examined. INTERVENTION: Laparoscopic weight reduction surgery. MAIN OUTCOME
      MEASURES: Prevalence of the MS as defined by the ATPIII (>3 of the following):
      waist circumference greater than 102 cm in men and 88 cm in women; serum
      triglyceride level of at least 150 mg/dL (1.70 mmol/L); high-density lipoprotein
      cholesterol level less than 40 mg/dL (1.04 mmol/L) in men and 50 mg/dL (1.30
      mmol/L) in women; blood pressure of at least 130/85 mm Hg; and serum glucose
      level of at least 110 mg/dL (6.11 mmol/L). RESULTS: Of 645 individuals, 337
      (52.2%) met the ATPIII definition of the MS. Individuals with the MS had
      significant differences in age (31.5 years vs 28.1 years), sex (127 [37.7%] of
      337 men vs 81 [26.3%] of 308 women), and many metabolic abnormalities compared
      with patients without the MS. Laparoscopic vertical banded gastroplasty was
      performed in 528 patients (81.9%) and laparoscopic gastric bypass in 117 (18.1%).
      A significant decrease in weight was found in both groups, but individuals who
      underwent laparoscopic gastric bypass lost significantly more weight (mean +/-
      SD, 38.4 +/- 14.4 kg vs 35.1 +/- 16.8 kg) and achieved a lower body mass index
      (29.3 +/- 4.8 vs 32.0 +/- 5.4) than individuals who underwent laparoscopic
      vertical banded gastroplasty. Substantial mean weight reduction (31.9%) of
      patients with the MS resulted in a substantial reduction of systolic (11.0 mm Hg)
      and diastolic (11.4 mm Hg) blood pressure and levels of glucose (46.1 mg/dL [2.56
      mmol/L]), triglycerides (196.6 mg/dL [2.22 mmol/L]), and total cholesterol (33.7
      mg/dL [0.88 mmol/L]) 1 year after surgery. These improvements resulted in a 95.6%
      resolution of the MS 1 year after surgery. There was no difference between
      operations (laparoscopic vertical banded gastroplasty or laparoscopic gastric
      bypass) in the resolution rate of the MS 1 year after surgery (95.0% vs 98.4%,
      respectively). CONCLUSION: The MS is prevalent in 52.2% of morbidly obese
      individuals enrolling in an obesity surgery program. Significant weight reduction
      1 year after surgery markedly improved all aspects of the MS and resulted in a
      cure rate of 95.6%. Obesity surgery performed by laparoscopic surgery is
      recommended for obese patients with the MS.

PMID- 15492150
TI  - Early effects of Helicobacter pylori infection in patients undergoing bariatric
      surgery.
AB  - HYPOTHESIS: Following weight loss surgery, many patients initially experience
      nonspecific foregut symptoms. Helicobacter pylori infection of the gastric
      remnant may be associated with foregut symptoms. DESIGN: Inception cohort.
      SETTING: University hospital. PATIENTS: Ninety-nine consecutive patients being
      evaluated for weight loss surgery. INTERVENTION: All patients underwent
      preoperative esophagogastroduodenoscopy and H pylori testing. MAIN OUTCOME
      MEASURES: Foregut symptoms were documented at routine post-weight loss surgery
      follow-up visits. RESULTS: Preoperatively, 24% of patients tested positive for H
      pylori. Postoperative foregut symptoms were significant in 48% of the H pylori
      positive group, and 19% of the H pylori-negative group (P = .02). This increase
      remained even after controlling for age, sex, preoperative presence of antritis,
      type of surgery performed, and body mass index (odds ratio, 3.6; 95% confidence
      interval,1.1-11.8). Patients with prolonged symptoms who tested positive for H
      pylori were given an eradication treatment. CONCLUSIONS: The prevalence of H
      pylori infection in patients undergoing weight loss surgery is high, and a
      significant proportion of them have postoperative foregut symptoms. Consideration
      should be given to H pylori treatment in these patients.

PMID- 15492151
TI  - Preferred mesh-based inguinal hernia repair in a teaching setting: results of a
      randomized study.
AB  - HYPOTHESIS: Surgeons' preferences for any of 3 methods of inguinal hernia repair
      are comparable in terms of operating time, incision length, perceived difficulty,
      and surgeon's satisfaction. DESIGN: Randomized patient-blinded study. SETTING:
      Teaching hospital. PATIENTS: A total of 334 patients randomized to receive 1 of
      the 3 repairs. INTERVENTIONS: Patients underwent hernia repair with the Prolene
      Hernia System, mesh plug repair, or Lichtenstein technique. MAIN OUTCOME
      MEASURES: Operating variables, surgeon's rating of satisfaction and difficulty,
      grade and experience of the operating team, and complications. RESULTS: The
      Lichtenstein technique took significantly the longest operating time (52 minutes
      vs 41 or 42 minutes; P<.001). The mesh plug repair scored the best results in
      difficulty and satisfaction. Overall, surgeons having performed more than 5
      procedures rated the repairs less difficult and with significantly more
      satisfaction (P<.001 and P = .001, respectively). The complication rate did not
      differ between the treatment groups. None of the operative findings was
      correlated to the outcome, except for adverse correlation with the body mass
      index. CONCLUSION: From a surgeon's point of view, the mesh plug repair is
      superior to the Lichtenstein technique and the Prolene Hernia System in terms of
      operating time, incision length, perceived difficulty, and surgeon's
      satisfaction.

PMID- 15492152
TI  - Risk factors for biliary complications after liver transplantation.
AB  - HYPOTHESIS: Biliary complications after liver transplantation can be predicted
      from perioperative factors. DESIGN: Retrospective analysis of data collected
      prospectively. SETTING: Tertiary referral center. PATIENTS: From October 5, 1991,
      through June 22, 2002, 230 patients received 241 consecutive orthotopic liver
      transplants. Patients were divided into those with (group 1) and those without
      (group 2) biliary complications. MAIN OUTCOME MEASURES: Postoperative outcomes,
      biliary leakage, and anastomotic stricture. RESULTS: The overall biliary
      complication rate was 20.7%, including bile leakage rate of 7.1% and anastomotic
      stricture rate of 16.2%. By means of univariate analysis, risk factors associated
      with biliary complications were preoperative serum bilirubin level (P = .003),
      international normalized ratio (P = .04), the use of stent or T-tube splinting of
      the anastomosis (P = .02), and the use of live-donor liver graft (P = .03).
      Stepwise logistic regression analysis demonstrated that the preoperative serum
      bilirubin level (relative risk [RR], 1.00), use of stent or T-tube splinting of
      the anastomosis (RR, 2.10), and use of live-donor liver graft (RR, 2.01) were
      independent risk factors predicting biliary complications after liver
      transplantation. Graft survival rates at 1, 3, and 5 years were 89.5%, 84.7%, and
      79.7%, respectively, in group 1 and 84.7%, 78.4%, and 75.1%, respectively, in
      group 2 (P>.05). Patient survival rates at 1, 3, and 5 years were 89.1%, 86.5%,
      and 86.5%, respectively, in group 1, and 86.1%, 82.8%, and 81.0%, respectively,
      in group 2 (P>.05). CONCLUSIONS: Preoperative serum bilirubin level and the use
      of stent or T-tube splinting of the anastomosis and live-donor liver grafts were
      independent risk factors for biliary complications after liver transplantation.
      We postulated that high preoperative serum bilirubin level reflected severe liver
      disease and difficult hemostasis, leading to inadvertent injury to the
      anastomosis during graft rotation or manipulation for hemostasis. The use of a
      stent or a T tube predisposes to more complications. Further technical refinement
      is necessary for biliary reconstruction in live-donor liver transplantation.

PMID- 15492153
TI  - A simple technique for identification and preservation of the hypogastric nerves
      during rectal surgery.
AB  - HYPOTHESIS: Rectal resection is associated with a risk of sexual dysfunction even
      when performed for benign disease, with the most frequent type resulting in
      retrograde ejaculation due to injury to the hypogastric nerves. DESIGN: A simple
      technique to identify and protect these nerves during rectal mobilization.
      SETTING: Exposure of the hypogastric plexus during rectal resection. CONCLUSION:
      Careful identification of the hypogastric nerves during rectal mobilization using
      the described technique may reduce injury to these nerves and related sexual
      dysfunction.

PMID- 15492154
TI  - From the lumen to the laparoscope.
AB  - Throughout the ages, the issues that have defined the management of disease
      processes have been particularly exemplified in the gastrointestinal tract. The
      use of gas lamps and candles with reflectors by Bozzini, Segalas, Cruise, and
      Fisher (19th century) allowed for some ingress into both the upper and lower
      gastrointestinal tract. Von Mikulicz, Leiter, Nitze, Kelling, and Jacobaeus
      contributed to the development of rigid instruments that could be used
      endoscopically or laparoscopically. Endoscopic efforts were amplified and
      extended by Rosenheim, Sternberg, Wolf, and, finally, Schindler, who not only
      introduced novel lens systems but also for the most part overcame the problems of
      flexibility and illumination. Bernheim, Ruddock, Veress, and Palmer made
      significant technical and clinical contributions to abdominal cavity exploration.
      The subsequent application of Hopkins and Kapany's work on optics, and the
      development by Hirschowitz and Curtiss of the flexible fiber optic endoscope,
      enabled the design of instruments that would allow the appropriate illumination
      and vision of both the farthest reaches of the bowel as well as the interior of
      the abdomen. Thus, the same endoscopic instruments coupled with a surgical
      interest in diagnostic laparotomy allowed for the evolution of minimally invasive
      surgery along a similar timescale. The cycle whereby diagnostic laparotomy in the
      early part of the century was supplanted by endoscopy and laparoscopy has now
      attained full circle whereby laparoscopy has evolved from a diagnostic procedure
      into one with major therapeutic applications and is perceived as the state-of-the
      art technique for a wide variety of operations, including appendectomy,
      cholecystectomy, hernia repair, fundoplication, splenectomy, colectomy, and
      gastrointestinal anastomoses.

PMID- 15492155
TI  - Image of the month. Slippage of stomach through an adjustable gastric lap-band.

PMID- 15492156
TI  - Extra credit.

PMID- 15492157
TI  - The preperitoneal space.

PMID- 15492158
TI  - Training to proficiency: aircraft to OR.

PMID- 15492159
TI  - Striving for imperfection: facing up to human error in medicine.

PMID- 15492160
TI  - Human error identification: an analysis of myringotomy and ventilation tube
      insertion.
AB  - OBJECTIVES: To use a human reliability assessment tool to identify commonly
      occurring errors during myringotomy and ventilation tube (VT) insertion and to
      quantify the likelihood of error occurrence. METHODS: Error-free task analysis
      for myringotomy and VT insertion was defined at the outset. Fifty-five
      consecutive myringotomy and VT insertion procedures were videotaped. The operator
      was either the senior author (S.S.M.H.) or a trainee in the specialist registrar
      or senior house officer grade. Three assessors (M.-L.M., M.S.W.L, and S.S.M.H.)
      blinded to operator identity independently evaluated each procedure.
      Interobserver agreement was calculated (kappa values). RESULTS: Twelve potential
      error types were identified. A total of 87 errors were observed in 55 procedures.
      In 53% of procedures (n = 29) multiple errors were identified. Seven percent of
      procedures (n = 4) were error free. The 4 most frequent errors identified were
      (1) failure to perform a unidirectional myringotomy incision (n = 37; 43%); (2)
      multiple attempts to place VT (n = 14; 16%); (3) multiple attempts to complete
      the myringotomy (n = 11; 13%); and (4) magnification setting too high (n = 11;
      13%). The human error probability was 0.13. Interobserver agreement as expressed
      by kappa statistics was high. CONCLUSIONS: Human error identification in this
      most common of otologic procedures is crucial to future error avoidance.
      Eliminating the 2 most common errors in this model will halve the human error
      probability. Extending the role of error analysis to error-based teaching as an
      educational tool has potential.

PMID- 15492161
TI  - Ambulatory tympanomastoid surgery in children: factors affecting hospital
      admission.
AB  - OBJECTIVE: To identify clinical factors associated with postoperative nausea and
      vomiting (PONV) and failure to discharge from the hospital on the day of surgery
      in children undergoing tympanomastoid surgery. DESIGN: Records of 144 children
      undergoing 152 tympanomastoid surgical procedures from July 1, 2001, through June
      30, 2002, were retrospectively reviewed and the data analyzed. SETTING: A
      tertiary care university-affiliated hospital. RESULTS: The mean +/- SD age of the
      cases was 11 +/- 3.7 years. Sixty-eight cases (45%) were middle ear procedures,
      while 84 cases (55%) were mastoid procedures. Forty-three cases (28%) were
      discharged home from the postanesthesia care unit (PACU), 55 cases (36%) were
      discharged on the day of surgery, and 142 cases (92%) were discharged home from
      the day surgery unit (DSU) within 23 hours after surgery. Patients who underwent
      mastoid procedures were more likely to require intravenous (IV) morphine sulfate
      in the PACU (75% vs 56%; P = .02) and were less likely to be discharged from PACU
      (15% vs 44%; P<.001) compared with patients who had middle ear procedures. In
      patients who underwent mastoid procedures, the presence of cholesteatoma (odds
      ratio, 1.9; 95% confidence interval, 1.0-3.7; P = .04) was associated with a
      higher likelihood of PONV. In both groups, the need for IV morphine sulfate to
      control pain on admission to DSU was associated with a higher occurrence of PONV.
      Factors that were significantly associated with failure to discharge from the
      hospital on the day of surgery were a pain score of 5 or greater, the presence of
      PONV, and the requirement of IV morphine sulfate on admission to DSU.
      CONCLUSIONS: Factors associated with higher risks of PONV and failure to
      discharge from the hospital on the day of surgery include the presence of
      cholesteatoma, a pain score of 5 or greater, and the requirement of IV morphine
      sulfate at the time admission to the DSU.

PMID- 15492162
TI  - Chinchilla middle ear epithelial mucin gene expression in response to
      inflammatory cytokines.
AB  - OBJECTIVES: To review the importance of mucin on a molecular level in the
      understanding of the pathophysiology of otitis media and to present new data
      demonstrating differential up-regulation of specific mucin genes during
      inflammation of middle ear epithelium. DESIGN: Primary chinchilla middle ear
      epithelial cultures (CMEECs) were established and exposed to tumor necrosis
      factor alpha and interleukin 1beta. Expression of chinchilla mucin genes 1, 2, 4,
      and 5AC was analyzed by means of reverse transcriptase-polymerase chain reaction
      after this exposure and compared with that of controls. Mucin secretion was also
      characterized by means of exclusion chromatography and liquid scintillation.
      RESULTS: The CMEECs exposed to interleukin 1beta and tumor necrosis factor alpha
      demonstrated significant up-regulation of mucin gene 2 (P = .005 and P = .007,
      respectively) and trends suggestive of up-regulation of mucin gene 5AC compared
      with the controls. These CMEECs also demonstrated significant increases in
      secretion of mucin compared with controls. Mucin genes 1 and 4 did not
      demonstrate up-regulation. CONCLUSIONS: In CMEECs, the inflammatory mediators
      tumor necrosis factor alpha and interleukin 1beta cause a differential up
      regulation and expression of mucin genes. Elucidating the effect of specific
      cytokines on the regulation of mucin secretion in the middle ear is vital to
      understanding the pathophysiology of otitis media. A greater understanding of
      these mechanisms and variations between individuals and pathogens has the
      potential to significantly alter the approach and management of otitis media in
      children and lead to novel therapeutic interventions.

PMID- 15492163
TI  - Audiometric findings in children with a large vestibular aqueduct.
AB  - OBJECTIVE: To characterize audiometric findings in children with a large
      vestibular aqueduct (LVA). DESIGN: Retrospective review. METHODS: Audiometric
      records of children with an isolated LVA, diagnosed by computed tomography of the
      temporal bone, from 1995 through 1998 were reviewed. RESULTS: Nineteen children
      had an isolated LVA in one or both ears. In all, 26 ears with an isolated LVA
      were identified. An LVA was seen in association with another inner ear anomaly in
      an additional 7 ears. The hearing impairment was sensorineural in 22 ears (85%)
      with an isolated LVA and mixed in 3 (12%). The hearing was normal in 1 ear. The
      sensorineural hearing impairment (SNHI) was moderate-severe in 12 ears (46%) and
      severe-profound in 10 ears (38%). Thirteen (50%) of 26 ears had a downsloping or
      high-frequency SNHI, and 8 (31%) of 26 ears had a midfrequency-peaked audiogram.
      Bilateral LVAs were seen in 7 children, 6 of whom had bilateral and asymmetrical
      SNHI. Of 12 patients with a unilateral LVA, 5 had bilateral SNHI. CONCLUSIONS: In
      this series, the children with LVAs typically had moderate-severe or worse SNHI.
      An unusual midfrequency-peaked audiogram was present in approximately one third
      of the study patients. The majority of the patients had a unilateral LVA;
      however, nearly 50% of the patients with a unilateral LVA had bilateral SNHI. The
      patients with bilateral LVAs generally had asymmetrical SNHI.

PMID- 15492164
TI  - Randomized, placebo-controlled evaluation of Cerumenex and Murine earwax removal
      products.
AB  - OBJECTIVE: To evaluate the efficacy of 2 ceruminolytic products, Cerumenex
      Eardrops (Purdue Frederick Company, Norwalk, Conn) and Murine Ear Drops (Abbott
      Laboratories, Abbott Park, Ill), in subjects with partial or complete occlusion
      of the ear canal due to cerumen. DESIGN: Randomized, subject- and observer-blind,
      placebo-controlled, clinical trial. SETTING: Corporate research clinic.
      PARTICIPANTS: From among 230 volunteers screened, 74 subjects (age, 22-66 [mean,
      45] years) were enrolled in the study. Participants had baseline occlusion levels
      of mild (n = 10), moderate (n = 26), or complete (n = 38) impairment of tympanic
      membrane visualization. INTERVENTIONS: Subjects were randomly assigned to 1 of 3
      treatments: Cerumenex (10% triethanolamine polypeptide oleate-condensate), Murine
      (6.5% carbamide peroxide), and a placebo, BSS Sterile Irrigating Solution (Alcon
      Laboratories Inc, Ft Worth, Tex). The test medication was instilled into 1
      occluded ear for up to two 15-minute applications. Following the treatment, the
      subject's ear was irrigated with 50 mL of lukewarm water delivered at low
      pressure via a WaterPik irrigator equipped with a Grossan irrigator tip. Main
      Outcome Measure The degree of occlusion, measured against a previously
      established 4-point scale, was assessed and recorded at baseline and after each
      instillation and irrigation procedure. RESULTS: Neither Cerumenex nor Murine was
      superior to saline placebo. By the end of treatment, 29.2%, 15.4%, and 41.7% of
      subjects treated with Cerumenex, Murine, and placebo, respectively, experienced
      resolution of cerumen occlusion. These values were not statistically
      significantly different from one another. CONCLUSION: The currently marketed
      ceruminolytic products, Cerumenex and Murine, are no more effective than a saline
      placebo in removing earwax.

PMID- 15492165
TI  - Diagnostic relevance of beta2-transferrin for the detection of cerebrospinal
      fluid fistulas.
AB  - OBJECTIVE: The beta(2)-transferrin assay is a specific method to identify
      cerebrospinal fluid (CSF). Hitherto, this test has not been widely used for the
      routine screening of patients with suspected CSF leakage. The purpose of this
      study was to investigate the clinical relevance of the identification of beta(2)
      transferrin by comparing the test results with other diagnostic measures and
      intraoperative findings. DESIGN: Case series. PATIENTS: Retrospective analysis of
      182 patients tested once or multiple times for beta(2)-transferrin. MAIN OUTCOME
      MEASURES: Information was obtained regarding different diagnostic procedures
      applied to diagnose CSF leakage. The effectiveness of those diagnostic measures
      was compared. RESULTS: The main indication to test for beta(2)-transferrin was
      posttraumatic rhinorrhea (25%), followed by spontaneous (22%) and postsurgical
      (22%) rhinorrhea. In 35 of 205 cases, beta(2)-transferrin was detected in the
      tested specimens. Thirteen of these required surgical intervention for treatment
      of the CSF fistula, and the leakage site was identified in all of them. Taking
      all results into consideration, the highest correlation was observed between the
      beta(2)-transferrin assay, intrathecal fluorescein application, and surgical
      exploration. CONCLUSIONS: The beta(2)-transferrin assay is a reliable method for
      confirming suspected CSF and should be used as a primary screening method in all
      patients with suspected CSF leakage. Although less invasive, the beta(2)
      transferrin assay almost matches the high sensitivity achieved by exploratory
      surgery and intrathecal application of fluorescein. However, the possibility of
      bias should be carefully considered, and in particular, negative results should
      be critically compared with clinical symptoms and with results from other
      diagnostic procedures.

PMID- 15492166
TI  - Prefabrication of composite grafts for long-segment tracheal reconstruction.
AB  - OBJECTIVE: To investigate the prefabrication of vascularized mucosa-lined
      composite grafts intended to replace circumferential tracheal defects. DESIGN:
      Plane grafts composed of ear cartilage and full-thickness oral mucosa were
      revascularized by the laterothoracic fascia. The use of meshed vs nonmeshed
      mucosa to improve the epithelial coverage was examined. We also investigated the
      creation of a vascular bed over the cartilage and the subsequent application of
      meshed mucosa. Macroscopic aspects, viability, and degree of mucosal lining were
      analyzed. SUBJECTS: Twenty male New Zealand white rabbits. INTERVENTIONS: Ten
      animals underwent placement of auricular cartilage under the laterothoracic
      fascia. Intact (group 1) or meshed mucosa (group 2) was applied over the fascia
      and protected by a silicone sheet. After 3 weeks, prefabricated grafts were
      removed for comparison. In 10 other animals, a sheet of perforated cartilage was
      placed under the laterothoracic fascia. Two weeks later, 5 grafts (group 3) were
      harvested. The remaining 5 grafts were reopened for mucosal application over the
      cartilage and revascularized for 3 additional weeks (group 4). RESULTS:
      Vascularized plane grafts were obtained in all groups. Mucosal lining increased
      significantly with meshed mucosa (14%-68%; mean, 40%) compared with nonmeshed
      mucosa (3%-15%; mean, 10%) (P = .008). Induction of a vascular bed over
      perforated cartilage was achieved, but survival of secondary implanted mucosa was
      variable. CONCLUSIONS: A reliable technique to prefabricate composite grafts with
      cartilaginous support and mucosal lining is presented. The use of meshed mucosa
      significantly improves epithelial coverage.

PMID- 15492167
TI  - Tracheal reconstruction using tissue-engineered cartilage.
AB  - OBJECTIVES: To determine whether rabbit cartilage can be tissue engineered using
      a polyglycolic acid (PGA) construct composed of PGA mesh, autologous
      chondrocytes, and alginate covalently linked with the cell adhesion sequence
      arginine-glycine-aspartic acid (RGD), and to investigate the feasibility of
      reconstructing tracheal defects using the PGA construct in conjunction with a
      bioabsorbable intratracheal stent. METHODS: Nineteen New Zealand White rabbits
      were used. Nine rabbits underwent subcutaneous implantation of 3 different PGA
      construct combinations: (1) PGA, autologous chondrocytes, and RGD-modified
      alginate; (2) PGA, autologous chondrocytes, and unmodified alginate; and (3) PGA
      and RGD-modified alginate. The remaining 10 animals underwent anterior tracheal
      reconstruction using fascia lata grafts and the complete PGA construct (PGA,
      autologous chondrocytes, and RGD-modified alginate). At the time of tracheal
      reconstruction, a poly-l-lactic acid intratracheal stent was placed in 5 of these
      latter animals. Rates of tracheal stenosis and mortality were compared with those
      of historical control animals. Histologic analysis was performed on the PGA
      constructs. RESULTS: In the subcutaneous implants, the PGA constructs made with
      chondrocytes (with and without RGD) demonstrated mature cartilage formation in 7
      (78%) of the 9 animals. No cartilage was seen in PGA constructs made without
      chondrocytes. Two of the 10 animals that underwent tracheal reconstruction with
      the complete PGA construct survived to 20 weeks and demonstrated patent airways,
      1 with a stent and 1 without a stent (80% overall mortality). Histologic analysis
      showed mature cartilage formation at the tracheal reconstruction site. Historical
      control animals that underwent reconstruction with fascia lata alone demonstrated
      the lowest overall mortality. CONCLUSIONS: Cartilage can be tissue engineered in
      rabbits using PGA mesh embedded with alginate-encapsulated autologous
      chondrocytes. It is also possible to reconstruct tracheal defects with this
      method of cartilage engineering, although the mortality rate in this study is
      high.

PMID- 15492168
TI  - Ambulatory powered intracapsular tonsillectomy and adenoidectomy in children
      younger than 3 years.
AB  - OBJECTIVES: (1) To assess the safety and efficacy of outpatient intracapsular
      tonsillectomy, which has been recently described as a less invasive means of
      treating obstructive tonsillar hypertrophy, in children younger than 3 years; and
      (2) to challenge the standard dictum that children younger than 3 years should be
      admitted to the hospital after tonsil and adenoid surgery. DESIGN: Retrospective
      cohort study via medical chart review and telephone interview. SETTING: Pediatric
      otolaryngology group practice with academic affiliation. Patients Children with
      symptomatic tonsillar and adenoid hypertrophy (n = 226) who underwent
      microdebrider-assisted intracapsular tonsillectomy between September 1, 2000, and
      October 1, 2002. METHODS: Comparison of study group (children <3 years old, n =
      38; mean age, 30.3 months; 20 boys and 18 girls) with control group (children >
      or =3 years, n = 188), measuring pain, oral intake, analgesic requirements,
      complications, need for readmission, and relief of symptoms. RESULTS: There were
      no statistically significant differences in pain, oral intake, or analgesic
      requirements. All children, regardless of age, were discharged home within 4
      hours of surgery. No child in either group required readmission, and there were
      no complications related to the time of discharge. Younger children experience
      equivalent symptomatic improvement. CONCLUSION: Children younger than 3 years may
      undergo intracapsular tonsillectomy as outpatients without sacrificing safety or
      efficacy.

PMID- 15492169
TI  - The risk of development of antimicrobial resistance in individual patients with
      chronic rhinosinusitis.
AB  - OBJECTIVE: To determine if individual patients with chronic rhinosinusitis (CRS)
      demonstrate an increasing prevalence of antimicrobial resistance over time.
      PATIENTS: A prospectively maintained database of microbiologic culture results
      for adult patients with CRS was sequentially analyzed, extracting patients who
      underwent multiple serial sinus cultures over time. Antimicrobial resistance
      patterns were identified and quantified for each bacterium. Sequential culture
      results were compared for individual patients to determine if increasing overall
      bacterial resistance, gram-positive resistance, gram-negative resistance, or a
      shift toward gram-negative organisms was manifested within individual patients.
      RESULTS: During a 7-year period, 90 adult patients were identified with 224
      serial cultures (mean, 2.5 cultures per patient) obtained, with a median time
      between cultures of 157 days. Four hundred twenty-nine organisms were isolated
      from these serial cultures, consisting of 255 gram-positive organisms, 120 gram
      negative organisms, 48 anaerobes, and 6 fungi. Pairwise analysis of sequential
      cultures revealed no significant trend toward increasing bacterial resistance
      within individual patients (P = .57, runs test). Similarly, no significant trend
      toward increasing gram-positive or gram-negative resistance was demonstrated.
      There was no shift toward gram-negative organisms (P>.15 for all). CONCLUSIONS:
      Individual patients with CRS do not necessarily develop increasing levels of
      bacterial resistance over time. The use of culture-directed antimicrobial therapy
      may "protect" against the development of sequentially increasing antimicrobial
      resistance for patients with CRS.

PMID- 15492170
TI  - The significance of serum soluble intercellular adhesion molecule 1 and
      transforming growth factor alpha in patients with nasopharyngeal carcinoma.
AB  - OBJECTIVE: To determine serum levels of soluble intercellular adhesion molecule 1
      (sICAM-1) and transforming growth factor alpha (TGF-alpha) in 51 patients with
      nasopharyngeal carcinoma before, during, and after radiation therapy (5-year
      follow-up period). RESULTS: The mean +/- SD serum levels of the 2 cytokines were
      found to be higher in patients before radiotherapy (sICAM-1, 369.6 +/- 123.7
      ng/mL; TGF-alpha, 36.6 +/- 24.6 ng/mL) than after radiotherapy (sICAM-1, 225.9 +/
      124.3 ng/mL; TGF-alpha, 20.2 +/- 22.3 ng/mL) (P<.05), and they were
      significantly higher in patients with recurrence (sICAM-1, 512.5 +/- 271.2 ng/mL;
      TGF-alpha, 48.2 +/- 23.4 ng/mL) and in those who died (sICAM-1, 542.6 +/- 245.4
      ng/mL; TGF-alpha, 50.2 +/- 28.8 ng/mL) than in patients with no recurrence (sICAM
      1, 217.9 +/- 116.4 ng/mL; TGF-d, 21.5 +/- 26.8 ng/mL) and in those who survived
      (sICAM-1, 209.4 +/- 167.2 ng/mL; TGF-alpha, 20.4 +/- 27.3 ng/mL) (P<.05). The
      increases in serum levels occurred approximately 3 months before relapse.
      CONCLUSION: We found that sICAM-1 and TGF-alpha levels are extremely useful
      markers for predicting illness, recurrence, and survival.

PMID- 15492171
TI  - Long-term quality-of-life evaluation after head and neck cancer treatment in a
      developing country.
AB  - OBJECTIVE: To evaluate the long-term quality of life of patients treated for head
      and neck cancer at a single institution in a developing country. DESIGN: Cross
      sectional analysis of a consecutive series of patients. SETTING: Tertiary cancer
      center hospital in Brazil. PATIENTS: Eligible subjects included patients treated
      between 1974 and 1999 for head and neck carcinoma who had a minimum disease-free
      survival of 2 years and who completed a Portuguese version of the University of
      Washington Quality of Life (UW-QOL) questionnaire. MAIN OUTCOME MEASURES:
      Descriptive analyses of the results and comparisons of the scores for each UW-QOL
      domain, stratified by tumor site, were performed using nonparametric tests.
      RESULTS: Findings from 344 patients were analyzed. Of the study population, 140
      (41%) had survived 2 to 5 years, 125 (36%) had survived 5 to 10 years, and 79
      (23%) had survived more than 10 years since treatment. Primary tumor sites were
      in the oral cavity in 43.3% of cases, the oropharynx in 20.9%, the larynx in
      32.0%, and the hypopharynx in 3.8%. In terms of treatment, 33.1% underwent
      surgery alone; 16.9%, radiotherapy alone; and 50% underwent combined treatment.
      Overall, 78.5% of the patients classified their own health as good or excellent.
      Stratified analysis showed that impairment in chewing and swallowing was more
      common in patients with oral and oropharyngeal tumors than in those with larynx
      and hypopharynx tumors, and speech impairment was more frequently related to
      patients with larynx and hypopharynx tumors than to those with oral and
      oropharynx tumors. In all tumor sites, the composite scores were significantly
      worse in advanced tumors than early stage tumors, but the use of combined
      treatment had the greatest negative impact on quality-of-life scores, after we
      adjusted for T and N stage with multivariable analyses (P<.001). CONCLUSIONS: The
      Portuguese version of the UW-QOL questionnaire was an effective tool to evaluate
      quality of life in a Brazilian population. Although many patients reported some
      limitations, most reported a good to excellent long-term quality of life.

PMID- 15492172
TI  - Morbidity following central compartment reoperation for recurrent or persistent
      thyroid cancer.
AB  - OBJECTIVE: To determine the incidence of recurrent laryngeal nerve injury and
      hypoparathyroidism, we reviewed our experience with central compartment
      reoperation. DESIGN: Patients underwent preoperative ultrasonography and magnetic
      resonance imaging of the neck. Ultrasound-guided fine-needle aspiration biopsy
      was performed and demonstrated evidence of tumor in 15 patients. At the time of
      surgery, hook wire electrodes were placed endoscopically into 1 or both vocal
      cords to monitor the integrity of the recurrent laryngeal nerve. PATIENTS: The
      study population comprised 20 patients who had undergone reoperative central
      compartment dissections between the years 1997 and 2001. There were 15 women and
      5 men whose mean age was 49.4 years. All of the patients had prior total or
      subtotal thyroidectomy, and 4 patients had prior neck dissections. A primary
      thyroid cancer recurrence in the thyroid bed was present in 7 patients, and the
      remainder of the patients had cytological evidence of paratracheal or mediastinal
      metastases. A single patient had evidence of distant metastases involving the
      lung. MAIN OUTCOME MEASURE: Short- and long-term postoperative morbidity.
      RESULTS: Of the 20 patients, 18 had histologic evidence of metastases to the
      paratracheal lymph nodes, whereas 8 patients had metastases involving the
      anterior mediastinal lymph nodes. The mean number of lymph nodes removed was 6.5,
      and the mean number of positive lymph nodes was 4.7. None of the patients with
      normal preoperative laryngeal function had postoperative recurrent laryngeal
      nerve paresis or paralysis. There were 18 patients with normal preoperative
      parathyroid function. Four patients developed transient postoperative
      hypocalcemia. All 4 patients with transient postoperative hypocalcemia are
      currently eucalcemic. A single patient continues to receive calcium and
      calcitriol supplementation 1 month following her third central compartment
      dissection for recurrent thyroid cancer. CONCLUSIONS: Reoperation for recurrent
      or persistent thyroid cancer presents a significant challenge. However,
      intraoperative recurrent laryngeal nerve monitoring and preservation of the
      vascular pedicle of the parathyroid glands has reduced the morbidity of
      reoperative central compartment dissections to acceptable levels. Revision
      surgery in the central compartment of the neck is compatible with successful
      eradication of recurrent thyroid cancers and acceptable morbidity.

PMID- 15492173
TI  - Laryngeal embryonal rhabdomyosarcoma: a case of cervical metastases 13 years
      after treatment and a 25-year review of existing literature.
AB  - Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood, the
      majority of which are of the embryonal rhabdomyosarcoma (ER) variety. Present day
      treatment protocols involve a combination of aggressive surgery, chemotherapy,
      and radiation therapy. Embryonal rhabdomyosarcoma of the larynx is rare and
      unlike ER of other regions exhibits excellent response to multimodality treatment
      without the need for extensive surgery. We report a case of cervical metastases
      in a 29-year-old man 13 years after treatment of his laryngeal ER. To our
      knowledge, this is the first reported case of late neck metastases in ER of the
      larynx and the second reported case of delayed presentation of recurrent disease.
      A 25-year review of all published reports of ER of the larynx was conducted that
      highlights the move toward organ preservation with the multimodality treatment
      protocols. Embryonal rhabdomyosarcoma of the larynx is highly responsive to
      combination chemoradiotherapy, allowing for excellent cure rates without the need
      for extensive surgery. Late relapses warrant long-term follow-up.

PMID- 15492174
TI  - Odontoma of the middle ear: case report with 25-year follow-up.
AB  - We report the 25-year follow-up on the first reported case of odontoma in the
      middle ear. Diagnosis of odontoma had been made on the basis of radiography films
      that showed a middle ear mass with multiple toothlike areas of radiopacity. No
      clinical intervention was recommended. At 25-year follow-up, audiometry showed
      progressive mixed hearing loss on the affected side and mild ipsilateral
      sensorineural hearing loss. Computed tomography better characterized the discrete
      mass, which was shaped similar to a dental crown. To avoid jeopardizing cochlear
      and facial nerve function, no surgical intervention was pursued, and we
      recommended use of a BiCROS (bilateral contralateral routing of signal) hearing
      aid.

PMID- 15492175
TI  - Treatment of adult subcondylar mandibular fractures: closed vs open vs endoscopic
      approach.

PMID- 15492176
TI  - Early mobilization advocated in subcondylar fractures.

PMID- 15492177
TI  - Considerations in subcondylar fracture management.

PMID- 15492178
TI  - Pathology quiz case: Kikuchi-Fujimoto disease.

PMID- 15492179
TI  - Radiology quiz case 1: double aortic arch with tracheal compression.

PMID- 15492180
TI  - Radiology quiz case 2: Kimura disease.

PMID- 15492181
TI  - Cytomegalovirus ulcer. Successful treatment with valganciclovir.

PMID- 15492182
TI  - Double-blind placebo-controlled study of autologous transplanted epidermal cell
      suspensions for repigmenting vitiligo.
AB  - OBJECTIVES: To investigate the efficacy of epidermal noncultured cellular
      grafting in patients with vitiligo and the role of postinflammatory, spontaneous,
      or UV-induced pigmentation in obtaining repigmentation. DESIGN: A prospective,
      randomized, double-blind, placebo-controlled study. SETTING: Ambulatory patients
      in an institutional practice. Patients were followed up for 3 to 12 months.
      PATIENTS: A total of 33 paired, symmetrically distributed leukodermic lesions,
      all resistant to therapy, were observed in 28 patients. Nineteen patients
      appeared to have a stable vitiligo (group 1), whereas there was doubt about the
      stability of the disease in 9 patients (group 2). INTERVENTION: After laser
      ablation, a hyaluronic acid-enriched cellular graft was applied to 1 lesion while
      the paired lesion received placebo. Three weeks later all lesions were exposed to
      UV irradiation twice per week for approximately 2 months. MAIN OUTCOME MEASURES:
      Primarily, the percentage of repigmentation was assessed after 3, 6, and 12
      months using a digital image analysis system. The repigmentation pattern was also
      evaluated after 1 and 3 months. RESULTS: A strongly significant difference
      between cellular grafts and placebo was observed after 3, 6, and 12 months
      (P<.001, P = .002, and P = .002, respectively). In group 1, repigmentation of at
      least 70% of the treated area was achieved in 55%, 57%, and 77% of the actively
      treated lesions 3, 6, and 12 months after treatment, whereas in group 2
      repigmentation of at least 70% of the treated area was not observed at any time
      point. The repigmentation pattern was diffuse in 94% of the responding patients.
      CONCLUSIONS: After a strict preoperative selection for disease stability,
      transplantation resulted in repigmentation of at least 70% of the treated area in
      most actively treated vitiligo lesions. Repigmentation was primarily caused by
      the transplanted melanocytes.

PMID- 15492183
TI  - Long-term follow-up study of segmental and focal vitiligo treated by autologous,
      noncultured melanocyte-keratinocyte cell transplantation.
AB  - OBJECTIVE: To evaluate long-term efficacy and safety of melanocyte-keratinocyte
      cell transplantation in the management of segmental and focal vitiligo. DESIGN: A
      simpler and modified method based on that of Olsson and Juhlin was performed.
      This method uses a shaved biopsy skin sample up to one tenth the size of the
      recipient area. The skin sample is incubated, and the cells are mechanically
      separated using trypsin-EDTA solution and then centrifuged to prepare a
      suspension. Cell suspension is then applied to the dermabraded depigmented skin
      area, and a collagen dressing is applied to keep it in place. PATIENTS: Fifty
      patients with segmental and 17 with focal vitiligo were treated. One patient with
      segmental and 2 with focal vitiligo did not attend any follow-up visits. The
      remaining patients were observed for a period of up to 5 years. INTERVENTION:
      Autologous, noncultured melanocyte-keratinocyte cell transplantation. MAIN
      OUTCOME MEASURE: Repigmentation was graded as excellent with 95% to 100%
      pigmentation, good with 65% to 94%, fair with 25% to 64%, and poor with 0% to 24%
      of the treated area. RESULTS: In the segmental vitiligo group, 41 patients (84%)
      showed excellent, 3 (6%) good, and 5 (10%) poor pigmentation, which was retained
      until the end of the respective follow-up period. In the focal vitiligo group, 11
      patients (73%) showed excellent, 1 (7%) fair, and 3 (20%) poor pigmentation,
      which was retained until the end of the respective follow-up period. CONCLUSIONS:
      Melanocyte-keratinocyte cell transplantation is a simple, safe, and effective
      surgical therapy. Patients with segmental and focal vitiligo can experience a
      prolonged disease-free period, which may extend through the rest of their lives.

PMID- 15492184
TI  - Treatment of undifferentiated vulvar intraepithelial neoplasia with 5% imiquimod
      cream: a prospective study of 12 cases.
AB  - OBJECTIVE: To assess the efficacy of 5% imiquimod cream on undifferentiated
      vulvar intraepithelial neoplasia (VIN), a disease caused by high-risk human
      papillomavirus. DESIGN: Prospective, uncontrolled study. SETTING: University
      hospital vulvar clinic. Patients Twelve consecutive patients treated with 5%
      imiquimod cream for undifferentiated VIN between March 1, 1999, and May 31, 2001.
      INTERVENTION: Self-application of 5% imiquimod cream, initially 3 times a week,
      then adjusted according to tolerance, for up to 7 months according to clinical
      response. MAIN OUTCOME MEASURES: Therapeutic response, clinically assessed by
      successive photographs and histologically confirmed for complete responders, was
      scored as complete, partial (> or =50% decrease in lesion size), or failure.
      Tolerance was evaluated at each visit. RESULTS: A total of 3, 4, and 5 patients
      achieved complete response, partial response (> or =75% reduction in lesion size
      for all such cases), and failure, respectively. Mean duration of treatment was
      3.6 months (37.3 applications), 5.0 months (50.7 applications), and 3.4 months
      (25.2 applications) for complete responders, partial responders, and failures,
      respectively. Follow-up after treatment was 5 to 18, 14 to 32, and 2 to 28
      months, respectively, with 1 partial responder lost to long-term follow-up. No
      patient developed invasive carcinoma. All but 2 patients experienced vulvar
      discomfort, resulting in treatment withdrawal for 3. Two patients had flulike
      symptoms. CONCLUSIONS: Imiquimod cream could be a therapeutic option for
      undifferentiated VIN. Although poorly tolerated, this self-applied treatment
      could spare patients, either totally or partially, the classic painful and
      sometimes mutilating treatments of VIN. Controlled, randomized studies are needed
      to evaluate its efficacy and tolerance.

PMID- 15492185
TI  - Association of HLA-DR4 (DRB1*0404) with human papillomavirus infection in
      patients with focal epithelial hyperplasia.
AB  - OBJECTIVES: To determine gene frequencies of HLA-DR alleles in 22 Mexican
      patients with focal epithelial hyperplasia and compare them with those present in
      ethnically matched healthy subjects, as well as to determine the types of human
      papillomavirus present in the lesions. DESIGN: Prospective and retrospective
      observational study. SETTING: Dermatology outpatient clinic in a general
      hospital. PATIENTS: Twenty-two patients with clinically and histologically
      confirmed focal epithelial hyperplasia seen within a 10-year period.
      INTERVENTIONS: None. MAIN OUTCOME MEASURES: Results of high-resolution DNA typing
      for HLA-DR alleles and biopsy for viral typing. RESULTS: HLA-DR4 (DRB1*0404) was
      significantly increased (P<.001; odds ratio, 3.9; 95% confidence interval, 1.86
      8.03). Seventeen (85%) of 20 patients had human papillomavirus subtype 13. The
      data on human papillomavirus differed from reports elsewhere that described
      association with human papillomavirus type 32. CONCLUSIONS: The HLA-DRB1*0404
      allele suggests that Amerindian populations are at risk, and in this group, the
      Mexican population studied was affected only by human papillomavirus type 13.

PMID- 15492186
TI  - Significance of dermoscopic patterns in detecting malignant melanoma on acral
      volar skin: results of a multicenter study in Japan.
AB  - OBJECTIVE: To determine diagnostic variables such as sensitivity and specificity
      of the major dermoscopic patterns observed in melanocytic lesions on acral volar
      skin, with particular attention to the significance of the parallel ridge pattern
      and irregular diffuse pigmentation in detecting acral melanoma. DESIGN:
      Multicenter, retrospective study. SETTING: University hospitals in Japan.
      PATIENTS: Patients with melanocytic lesions on acral volar skin. A total of 712
      melanocytic lesions (103 malignant melanomas, including 36 in situ lesions, and
      609 melanocytic nevi) were consecutively collected from the files of 3 hospitals.
      Diagnoses of all the lesions had been determined histopathologically.
      INTERVENTIONS: Dermoscopic examination. MAIN OUTCOME MEASURES: The sensitivity,
      specificity, positive predictive value, negative predictive value, and diagnostic
      accuracy of the major dermoscopic patterns seen in benign and malignant
      melanocytic lesions on acral volar skin. RESULTS: The parallel ridge pattern and
      irregular diffuse pigmentation showed extremely high specificity (99.0% and
      96.6%, respectively) and very high negative predictive value (97.7% and 97.5%,
      respectively) in malignant melanoma. For melanoma in situ, the positive
      predictive value and diagnostic accuracy of the parallel ridge pattern were
      significantly higher than those of irregular diffuse pigmentation (P = .009 and P
      = .006, respectively). In melanocytic nevi, the specificity and positive
      predictive value of the parallel furrow pattern and/or the latticelike pattern
      were found to be very high (93.2% and 98.3%, respectively). CONCLUSIONS:
      Dermoscopy is immensely helpful in differentiating malignant melanomas from
      melanocytic nevi on acral volar skin. Moreover, the parallel ridge pattern aids
      in detecting acral melanomas in early, curable stages.

PMID- 15492187
TI  - Contact sensitivity in patients with leg ulcerations: a North American study.
AB  - OBJECTIVES: (1) To determine the prevalence of allergen sensitivity in patients
      with past or present leg ulcers in 2 North American study centers vs European
      study findings and the North American Contact Dermatitis Group (NACDG) database
      and (2) to delineate a standard battery of allergens for patch testing in North
      American patients that is representative of the newer dressings and wound care
      products. DESIGN: Fifty-four patients, with or without dermatitis, were
      prospectively entered in the study. The patients were patch tested to the NACDG
      standard series and a comprehensive supplemental series of 52 allergens. SETTING:
      Wound healing clinics at Boston University Roger Williams Medical Center and
      University of Ottawa. RESULTS: Sixty-three percent (n = 34) of patients had 1 or
      multiple positive patch test results, and 37% (n = 20) had no positive patch test
      result. The most common allergens were Myroxylon pereirae (balsam of Peru) (30%
      [16/54]), bacitracin (24% [13/54]), fragrance mix (20% [11/54]), wood tar mix
      (20% [11/54]), propylene glycol (14% [7/52]), neomycin sulfate (13% [7/54]),
      benzalkonium chloride (13% [7/54]), carba mix (11% [6/54]), nickel sulfate (11%
      [6/54]), and control gel hydrocolloid (11% [6/54]). CONCLUSIONS: Comparable to
      European study findings, there is a high incidence of positive patch test results
      in patients with past or present leg ulcerations. The incidences of the most
      common allergens in our patient population were higher than those seen in the
      NACDG, except for nickel. Using a modified leg ulcer series along with the
      standard NACDG series is important in evaluating patients with leg ulcers.

PMID- 15492188
TI  - Skin blood flow in diabetic dermopathy.
AB  - BACKGROUND: Diabetic dermopathy has been termed the most common cutaneous finding
      in diabetes, occurring in as many as 40% of diabetic patients older than 50
      years. Using laser Doppler technology, we tested the hypothesis that dermopathy
      lesions represented areas of cutaneous ischemia. DESIGN: A survey of cutaneous
      blood flow in diabetic patients with dermopathy and comparison of values with
      those in nondiabetic patients. SETTING: Outpatient clinic specializing in
      diabetes. PATIENTS: A consecutive sample of 61 diabetic patients (52 men and 9
      women; mean +/- SEM age, 58 +/- 2 years) with dermopathy had blood flow
      measurements performed at the sites of dermopathy and at contiguous uninvolved
      sites. Flow values were also determined at several reference sites and compared
      with those in 41 nondiabetic control subjects (30 men and 11 women; mean age, 53
      +/- 3 years). RESULTS: Heat-stimulated blood flow values at the knee, ankle, and
      toe were about 50% lower for the dermopathy patients than for the nondiabetic
      controls. Yet, despite their reduced skin blood flow reserve, the dermopathy
      lesions did not show relative ischemia. At the basal temperature of 35 degrees C,
      flow was 1.1 +/- 0.1 mL /min per 100 g of tissue in apparently normal skin vs 2.2
      +/- 0.2 at dermopathy sites; at 44 degrees C, flow at the normal sites was 7.9 +/
      0.3 mL /min per 100 g of tissue vs 12.9 +/- 0.6 at dermopathy sites (P<.01 for
      both comparisons). CONCLUSIONS: Although patients with diabetic dermopathy
      exhibited reduced skin blood flow compared with nondiabetic volunteers, flow
      levels were considerably higher at the dermopathy sites than at contiguous
      uninvolved skin sites. These results refute the hypothesis that diabetic
      dermopathy represents local ischemia. However, it is still possible that the
      scarring represented by dermopathy lesions is related to decreased skin perfusion
      due to diabetes.

PMID- 15492189
TI  - Localized longitudinal erythronychia: diagnostic significance and physical
      explanation.
AB  - BACKGROUND: Longitudinal erythronychia (LE) is a term for red streaks in the
      nail. We describe the range of diseases manifested by localized (single or bifid)
      LE and explain the underlying physical changes. OBSERVATIONS: Longitudinal
      erythronychia can be multiple or localized. Multiple lesions typically indicate
      an inflammatory disease such as lichen planus. When localized, they may be a
      single or bifid streak arising through a benign or malignant neoplasm, scarring
      of the dermis or epidermis, or the first stage of an inflammatory process that
      may evolve into multiple LE. Excision of a localized LE may provide a diagnosis
      and cure. Incisional matrix biopsy of multiple LE may provide a diagnosis.
      Clinical manifestation of LE arises through reduced compression of the nail bed
      due to loss of bulk of the nail plate with a groove on the undersurface. A streak
      of thinned nail then allows an enhanced view of a corresponding streak of
      engorged nail bed. The reduction in nail thickness renders it more fragile with a
      tendency to split distally. CONCLUSIONS: Understanding LE can assist in diagnosis
      and explanation to the patient. Localized LE may represent a focal tumor or
      dysplastic process.

PMID- 15492190
TI  - Corticosteroid treatment for melanoma-associated retinopathy: effect on visual
      acuity and electrophysiologic findings.
AB  - BACKGROUND: Visual disturbance in the course of melanoma is rare. Specific
      localized metastases and drug toxic effects are frequently the cause. Recognition
      of a retinopathy raises several questions when the diagnosis of melanoma
      associated retinopathy (MAR) can be confirmed. Descriptions of such patients in
      dermatologic literature are rare and deserve attention because therapeutic
      decisions are mandatory. OBSERVATIONS: A 70-year-old woman had a first melanoma
      in 1985 and a second primary melanoma in 1994. Axillary lymph node involvement
      occurred in November 2000, leading to surgery and chemotherapy. In December 2001,
      she had sudden bilateral visual loss, with shimmering blobs of color and
      flickering photopsias. Computed tomography and cerebral magnetic resonance
      imaging ruled out localized tumor on the eyes or optic nerves or evolution of
      disease. Ophthalmologic examination revealed a bilateral posterior uveitis, with
      hyalitis and progressive destruction of retinal pigment. The electrophysiologic
      data confirmed the diagnosis of MAR. Symptoms improved after systemic
      corticosteroid therapy, with no relapse after tapering doses despite worsening of
      melanoma. CONCLUSIONS: As a rare paraneoplastic visual syndrome possibly leading
      to blindness, MAR is characterized by bipolar cell involvement without
      photoreceptor cell impairment. Also, MAR is linked to the presence of
      autoantibodies directed against melanoma antigens that cross-react with the rod
      bipolar cells of the retina. Corticosteroid therapy is rarely beneficial. Our
      case of MAR is noteworthy because it involved a woman, was associated with an
      uveitis, and improved with corticosteroid therapy.

PMID- 15492191
TI  - Hypertrophic lichen planus-like reactions combined with infundibulocystic
      hyperplasia: pathway to neoplasia.
AB  - BACKGROUND: Retinoids have the capacity to accelerate the involution of multiple
      keratoacanthomas, including unusual variants such as keratoacanthoma marginatum
      centrifugum and keratoacanthoma en plaque that may persist and be associated with
      progressive growth and provide difficulties in diagnosis and management.
      OBSERVATIONS: We describe 3 patients who had unusual infiltrated and keratotic
      plaques affecting the lower legs or nasolabial area that persisted or recurred
      that may be related to this group of unusual keratoacanthomas. The 3 patients had
      differing clinical lesions that did not resemble classic keratoacanthomas, but
      were linked by their biopsy findings of hypertrophic lichen planus-like reaction
      and pseudoepitheliomatous hyperplasia with a prominent infundibulocystic
      component that progressed to multiple keratoacanthomas or infundibulocystic
      squamous cell carcinoma. Polymerase chain reaction analysis of biopsy material
      from 2 patients failed to detect human papillomavirus. All 3 presentations
      provided a therapeutic dilemma, but responded rapidly to acitretin treatment at a
      dosage of 10 to 25 mg daily, which was continued for 15 to 24 months.
      CONCLUSIONS: These cases illustrate an unusual reaction pattern that is
      hypertrophic lichen planus-like but, instead of evolving to classic lichen
      planus, progresses to infundibulocystic hyperplasia and the development of
      multiple keratoacanthomas or infundibulocystic squamous cell carcinomas.
      Retinoids represent a therapeutic option for this difficult clinical problem and
      may obviate repeated and extensive surgery.

PMID- 15492192
TI  - Herpes zoster in the first year of life following postnatal exposure to varicella
      zoster virus: four case reports and a review of infantile herpes zoster.
AB  - BACKGROUND: Herpes zoster, a painful vesicular dermatomal eruption, is the result
      of reactivation of the varicella-zoster virus (VZV) from infected sensory
      ganglia. Traditionally, it is considered to be a disease of adults, in contrast
      to primary infection with VZV, which tends to occur mainly in children.
      OBSERVATIONS: We report 4 cases of infantile herpes zoster in healthy
      immunocompetent children, all of whom were exposed to primary varicella infection
      within the first few months of life. A review of 62 cases from the literature
      reveals that postnatally acquired herpes zoster is less common than intrauterine
      infection (31% [n = 19] vs 69% [n = 43]) and that there is a 1.5:1 male
      predominance. All dermatomes are equally affected. CONCLUSIONS: Although
      uncommon, herpes zoster can develop in immunocompetent children as young as a few
      weeks of age and should be considered in the differential diagnosis of vesicular
      eruptions in infants. Most frequently, it is the result of intrauterine VZV
      infection, but it can be secondary to postnatal exposure to VZV at an early age.

PMID- 15492193
TI  - What are the needs for transplantation treatment in vitiligo, and how good is it?

PMID- 15492194
TI  - Hyperpigmented patches on the tongue of a young girl. Pigmented fungiform
      papillae of the tongue.

PMID- 15492195
TI  - A red-brown plaque on the nape. Solitary mastocytoma.

PMID- 15492196
TI  - Hyperkeratotic plaques on the palms and soles. Palmoplantar lichen planus,
      hyperkeratotic variant.

PMID- 15492197
TI  - Generalized exfoliative erythroderma since birth. Netherton syndrome.

PMID- 15492199
TI  - Is topical tacrolimus really an effective therapy for Hailey-Hailey disease?

PMID- 15492198
TI  - Comparison of 15% azelaic acid gel and 0.75% metronidazole gel for the topical
      treatment of papulopustular rosacea.

PMID- 15492200
TI  - Efficacy and safety of 5% imiquimod cream in treating patients with multiple
      superficial basal cell carcinomas.

PMID- 15492201
TI  - Sentinel lymph node biopsy for high-risk cutaneous squamous cell carcinoma of the
      head and neck.

PMID- 15492202
TI  - 5% imiquimod cream for the treatment of large superficial basal cell carcinoma.

PMID- 15492203
TI  - Disseminated granuloma annulare resolved with the T-cell modulator efalizumab.

PMID- 15492204
TI  - Leflunomide in psoriasis and psoriatic arthritis: a preliminary study.

PMID- 15492205
TI  - Analysis of risk factors in psoriatic patients with methotrexate-induced
      increases in transaminase levels.

PMID- 15492206
TI  - Dermoscopy of pigmented purpuric dermatoses (lichen aureus): a useful tool for
      clinical diagnosis.

PMID- 15492207
TI  - Efficacy of the 308-nm excimer laser in the treatment of mycosis fungoides.

PMID- 15492208
TI  - Modification of a device and its application for intralesional cryosurgery of old
      recalcitrant keloids.

PMID- 15492209
TI  - Dermoscopy of keratinocytic neoplasms: subpatterns of seborrheic keratoses.

PMID- 15492210
TI  - Triggered amplification by hybridization chain reaction.
AB  - We introduce the concept of hybridization chain reaction (HCR), in which stable
      DNA monomers assemble only upon exposure to a target DNA fragment. In the
      simplest version of this process, two stable species of DNA hairpins coexist in
      solution until the introduction of initiator strands triggers a cascade of
      hybridization events that yields nicked double helices analogous to alternating
      copolymers. The average molecular weight of the HCR products varies inversely
      with initiator concentration. Amplification of more diverse recognition events
      can be achieved by coupling HCR to aptamer triggers. This functionality allows
      DNA to act as an amplifying transducer for biosensing applications.

PMID- 15492211
TI  - Identification of alternative splicing regulators by RNA interference in
      Drosophila.
AB  - Alternative splicing is thought to be regulated by nonspliceosomal RNA binding
      proteins that modulate the association of core components of the spliceosome with
      the pre-mRNA. Although the majority of metazoan genes encode pre-mRNAs that are
      alternatively spliced, remarkably few splicing regulators are currently known.
      Here, we used RNA interference to examine the role of >70% of the Drosophila RNA
      binding proteins in regulating alternative splicing. We identified 47 proteins as
      splicing regulators, 26 of which have not previously been implicated in
      alternative splicing. Many of the regulators we identified are nonspliceosomal
      RNA-binding proteins. However, our screen unexpectedly revealed that altering the
      concentration of certain core components of the spliceosome specifically
      modulates alternative splicing. These results significantly expand the number of
      known splicing regulators and reveal an extraordinary richness in the mechanisms
      that regulate alternative splicing.

PMID- 15492212
TI  - Kinetic efficiency of endocytosis at mammalian CNS synapses requires
      synaptotagmin I.
AB  - At nerve terminals, synaptic vesicle components are retrieved from the cell
      surface and recycled for local reuse soon after exocytosis. The kinetics of this
      coupling is critical for the proper functioning of synapses during repetitive
      action potential firing, because deficiencies in this process lead to abnormal
      depletion of the releasable vesicle pool. Although the molecular basis of this
      coupling is poorly understood, numerous biochemical data point to a role for
      synaptotagmin I (SytI), an essential synaptic vesicle protein required for fast
      calcium-dependent exocytosis. Here, using synapto-pHluorin in an approach that
      allows the dissection of endocytosis and exocytosis into separate components
      during periods of stimulation, we examined exocytic-endocytic coupling in
      synapses from SytI knockout mice and their WT littermates. We show that
      endocytosis is significantly impaired in the absence of SytI with the relative
      rates of endocytosis compared with exocytosis reduced approximately 3-fold with
      respect to WT. Thus, in addition to regulating exocytosis, SytI also controls the
      kinetic efficiency of endocytosis at nerve terminals.

PMID- 15492213
TI  - grb2 heterozygosity rescues embryonic lethality but not tumorigenesis in pten+/-
      mice.
AB  - PTEN is a tumor suppressor gene implicated in both sporadic cancers and inherited
      tumor-prone syndromes. Here we show that pten+/- mice display a partially
      penetrant embryonic lethality. This lethality is associated with defects in both
      neural and placental development. Notably, this lethality is completely rescued
      by grb2 haploinsufficiency. In contrast, grb2 heterozygosity did not alter
      tumorigenesis in either pten+/- or T cell-specific pten-/- mice. grb2-/hypomorph
      murine embryonic fibroblasts (MEFs) show decreased activation of both PKB and Erk
      upon stimulation with epidermal growth factor, whereas grb2-/hypomorph; pten+/-
      MEFs activate PKB but not Erk normally. Similarly, grb2-/hypomorph fibroblasts
      die in low serum, and this phenotype is rescued by pten haploinsufficiency.
      Activation of both PKB and Erk as well as survival in low serum-containing media
      are all rescued by reexpression of Grb2 containing mutations within the N
      terminal Src homology 3 (SH3) domain, but not by C-terminal SH3 domain mutants.
      The N-terminal SH3 domain mutants fail to bind to Sos, whereas the C-terminal SH3
      domain mutants fail to bind to Gab1, suggesting that Erk and PKB activation in
      fibroblasts in response to epidermal growth factor depends on Gab1 or other C
      terminal SH3 domain-interacting proteins, but not on Sos. Thus,
      PTEN/phosphatidylinositol 3' kinase signaling requires Grb2 during both embryonic
      development and fibroblast survival, but Grb2 heterozygosity does not effect
      tumorigenesis in pten-deficient mice. In fibroblasts, survival signals emanating
      from the epidermal growth factor receptor appear to be PKB-dependent, and this
      activation depends on the C-terminal SH3 domain of Grb2, likely through the
      interaction of Grb2 with Gab1.

PMID- 15492214
TI  - Evidence for cooler European summers during periods of changing meltwater flux to
      the North Atlantic.
AB  - We analyzed fossil chironomids (nonbiting midges) and pollen in two lake-sediment
      records to reconstruct and quantify Holocene summer-temperature fluctuations in
      the European Alps. Chironomid and pollen records indicate five centennial-scale
      cooling episodes during the early- and mid-Holocene. The strongest temperature
      declines of approximately 1 degrees C are inferred at approximately 10,700-10,500
      and 8,200-7,600 calibrated 14C years B.P., whereas other temperature fluctuations
      are of smaller amplitude. Two forcing mechanisms have been presented recently to
      explain centennial-scale climate variability in Europe during the early- and mid
      Holocene, both involving changes in Atlantic thermohaline circulation. In the
      first mechanism, changes in meltwater flux from the North American continent to
      the North Atlantic are responsible for changes in the Atlantic thermohaline
      circulation, thereby affecting circum-Atlantic climate. In the second mechanism,
      solar variability is the cause of Holocene climatic fluctuations, possibly
      triggering changes in Atlantic thermohaline overturning. Within their dating
      uncertainty, the two major cooling periods in the European Alps are coeval with
      substantial changes in the routing of North American freshwater runoff to the
      North Atlantic, whereas quantitatively, our climatic reconstructions show a poor
      agreement with available records of past solar activity. Thus, our results
      suggest that, during the early- and mid-Holocene, freshwater-induced Atlantic
      circulation changes had stronger influence on Alpine summer temperatures than
      solar variability and that Holocene thermohaline circulation reductions have led
      to summer-temperature declines of up to 1 degrees C in central Europe.

PMID- 15492215
TI  - Proteomic analysis identifies that 14-3-3zeta interacts with beta-catenin and
      facilitates its activation by Akt.
AB  - beta-Catenin is a central effector of Wnt signaling in embryonic and stem cell
      development and in tumorigenesis. Here, through a mass spectrometric analysis of
      a beta-catenin protein complex, we identified 12 proteins as putative beta
      catenin interactors. We show that one of them, 14-3-3zeta, enhances beta-catenin
      dependent transcription by maintaining a high level of beta-catenin protein in
      the cytoplasm. More importantly, 14-3-3zeta facilitates activation of beta
      catenin by the survival kinase Akt and colocalizes with activated Akt in
      intestinal stem cells. We propose that Akt phosphorylates beta-catenin, which
      results in 14-3-3zeta binding and stabilization of beta-catenin, and these
      interactions may be involved in stem cell development.

PMID- 15492216
TI  - Improvement of comparative model accuracy by free-energy optimization along
      principal components of natural structural variation.
AB  - Accurate high-resolution refinement of protein structure models is a formidable
      challenge because of the delicate balance of forces in the native state, the
      difficulty in sampling the very large number of alternative tightly packed
      conformations, and the inaccuracies in current force fields. Indeed, energy-based
      refinement of comparative models generally leads to degradation rather than
      improvement in model quality, and, hence, most current comparative modeling
      procedures omit physically based refinement. However, despite their inaccuracies,
      current force fields do contain information that is orthogonal to the
      evolutionary information on which comparative models are based, and, hence,
      refinement might be able to improve comparative models if the space that is
      sampled is restricted sufficiently so that false attractors are avoided. Here, we
      use the principal components of the variation of backbone structures within a
      homologous family to define a small number of evolutionarily favored sampling
      directions and show that model quality can be improved by energy-based
      optimization along these directions.

PMID- 15492217
TI  - A class of eukaryotic GTPase with a punctate distribution suggesting multiple
      functional replacements of translation elongation factor 1alpha.
AB  - Translation elongation factor 1alpha (EF-1alpha, or EF-Tu in bacteria) is a
      highly conserved core component of the translation machinery that is shared by
      all cellular life. It is part of a large superfamily of GTPases that are involved
      in translation initiation, elongation, and termination, as well as several other
      cellular functions. Eukaryotic EF-1alpha (eEF-1alpha) is well studied and widely
      sampled and has been used extensively for phylogenetic analyses. It is generally
      thought that such highly conserved and functionally integrated proteins are
      unlikely to be involved in events such as lateral gene transfer or ancient
      duplication and gene sorting, which would undermine phylogenetic reconstruction.
      Here we describe a GTPase called EF-like (EFL), which is very similar to, but
      also distinct from, canonical eEF-1alpha. EFL is found in a wide variety of
      eukaryotes (dinoflagellates, haptophytes, cercozoa, green algae,
      choanoflagellates, and fungi), but its distribution is punctate: organisms that
      possess EFL are not closely related to one another, and EFL appears to be absent
      from the closest relatives of organisms that do possess it. Moreover, in most
      genomes where EFL is present, canonical eEF-1alpha appears to be absent. Analysis
      of functional divergence suggests that, whereas EFL is divergent in general,
      putative functional binding sites involved in translation are not significantly
      divergent as a whole. Altogether, it appears that EFL has replaced eEF-1alpha
      several times independently. This finding could be an indication of an ancient
      paralogy or, more likely, eukaryote-to-eukaryote lateral gene transfer.

PMID- 15492218
TI  - Myelin proteolipid protein-specific CD4+CD25+ regulatory cells mediate genetic
      resistance to experimental autoimmune encephalomyelitis.
AB  - SJL mice are highly susceptible to experimental autoimmune encephalomyelitis
      (EAE) induced with myelin proteolipid protein (PLP) peptide 139-151, whereas H-2
      congenic B10.S mice are resistant. Immunodominance and susceptibility to EAE are
      associated with a high precursor frequency of PLP 139-151-specific T cells in the
      naive repertoire of SJL mice. To understand the mechanism of EAE resistance in
      B10.S mice, we determined the precursor frequency of PLP 139-151-reactive T cells
      in both strains by using IAs/PLP 139-151 tetramers. SJL and B10.S mice had
      similar frequencies of tetramer-reactive T cells in the naive peripheral
      repertoire. However, in SJL mice, the majority of PLP 139-151 tetramer-positive
      cells were in the CD4+CD25- population, whereas there were more tetramer-positive
      cells in the CD4+CD25+ population of B10.S mice. Depletion of CD4+CD25+ cells in
      vivo facilitated the expansion of PLP 139-151-reactive cells with production of T
      helper 1 cytokines in EAE-resistant B10.S mice. Furthermore, anti-CD25 Ab
      treatment before immunization resulted in EAE induction in these otherwise
      resistant mice. These data indicate an important role for autoantigen-specific
      CD4+CD25+ cells in genetic resistance to autoimmunity.

PMID- 15492219
TI  - Coding single-nucleotide polymorphisms associated with complex vs. Mendelian
      disease: evolutionary evidence for differences in molecular effects.
AB  - Most Mendelian diseases studied to date arise from mutations that lead to a
      single amino acid change in an encoded protein. An increasing number of complex
      diseases have also been associated with amino acid-changing single-nucleotide
      polymorphisms (coding SNPs, cSNPs), suggesting potential similarities between
      Mendelian and complex diseases at the molecular level. Here, we use two different
      evolutionary analyses to compare Mendelian and complex disease-associated cSNPs.
      In the first, we estimate the likelihood that a specific amino acid substitution
      in a protein will affect the protein's function, by using amino acid substitution
      scores derived from an alignment of related protein sequences and statistics from
      hidden Markov models. In the second, we use standard Ka/Ks ratios to make
      comparisons at the gene, rather than the individual amino acid, level. We find
      that Mendelian disease cSNPs have a very strong tendency to occur at highly
      conserved amino acid positions in proteins, suggesting that they generally have a
      severe impact on the function of the protein. Perhaps surprisingly, the
      distribution of amino acid substitution scores for complex disease cSNPs is
      dramatically different from the distribution for Mendelian disease cSNPs, and is
      indistinguishable from the distribution for "normal" human variation. Further,
      the distributions of Ka/Ks ratios for human and mouse orthologs indicate greater
      positive selection (or less negative selection) pressure on complex disease
      associated genes, on average. These findings suggest that caution should be
      exercised when using Mendelian disease as a model for complex disease, at least
      with respect to molecular effects on protein function.

PMID- 15492220
TI  - The contribution of epistasis to the architecture of fitness in an RNA virus.
AB  - The tendency for genetic architectures to exhibit epistasis among mutations plays
      a central role in the modern synthesis of evolutionary biology and in theoretical
      descriptions of many evolutionary processes. Nevertheless, few studies
      unquestionably show whether, and how, mutations typically interact. Beneficial
      mutations are especially difficult to identify because of their scarcity.
      Consequently, epistasis among pairs of this important class of mutations has, to
      our knowledge, never before been explored. Interactions among genome components
      should be of special relevance in compacted genomes such as those of RNA viruses.
      To tackle these issues, we first generated 47 genotypes of vesicular stomatitis
      virus carrying pairs of nucleotide substitution mutations whose separated and
      combined deleterious effects on fitness were determined. Several pairs exhibited
      significant interactions for fitness, including antagonistic and synergistic
      epistasis. Synthetic lethals represented 50% of the latter. In a second set of
      experiments, 15 genotypes carrying pairs of beneficial mutations were also
      created. In this case, all significant interactions were antagonistic. Our
      results show that the architecture of the fitness depends on complex interactions
      among genome components.

PMID- 15492221
TI  - Prodrugs of bisthiazolium salts are orally potent antimalarials.
AB  - We created neutral antimalarial prodrugs that deliver bisthiazolium compounds
      with antimalarial activity in the nanomolar range. These drugs primarily affect
      early intraerythrocytic stages through rapid, nonreversible cytotoxicity. The
      compounds are suitable for both parenteral and oral use and plasma promotes rapid
      conversion of the prodrug into the drug. We demonstrate that very low doses offer
      protection in a murine model of malaria. The drugs show great potential for
      curing high parasitemia with short-course treatments. Oral administration of the
      TE3 prodrug completely cures Plasmodium cynomolgi infection in rhesus monkeys.
      The drugs specifically accumulate inside infected erythrocytes, block
      phosphatidylcholine biosynthesis, and interact with hemozoin. To our knowledge,
      this class of compounds represents one of the most potent antimalarials tested to
      date. These unique properties signal a promising future for this class of
      antimalarial.

PMID- 15492222
TI  - Feeding status and serotonin rapidly and reversibly modulate a Caenorhabditis
      elegans chemosensory circuit.
AB  - Serotonin (5-HT) modulates synaptic efficacy in the nervous system of vertebrates
      and invertebrates. In the nematode Caenorhabditis elegans, many behaviors are
      regulated by 5-HT levels, which are in turn regulated by the presence or absence
      of food. Here, we show that both food and 5-HT signaling modulate chemosensory
      avoidance response of octanol in C. elegans, and that this modulation is both
      rapid and reversible. Sensitivity to octanol is decreased when animals are off
      food or when 5-HT levels are decreased; conversely, sensitivity is increased when
      animals are on food or have increased 5-HT signaling. Laser microsurgery and
      behavioral experiments reveal that sensory input from different subsets of
      octanol-sensing neurons is selectively used, depending on stimulus strength,
      feeding status, and 5-HT levels. 5-HT directly targets at least one pair of
      sensory neurons, and 5-HT signaling requires the Galpha protein GPA-11.
      Glutamatergic signaling is required for response to octanol, and the GLR-1
      glutamate receptor plays an important role in behavioral response off food but
      not on food. Our results demonstrate that 5-HT modulation of neuronal activity
      via G protein signaling underlies behavioral plasticity by rapidly altering the
      functional circuitry of a chemosensory circuit.

PMID- 15492223
TI  - A system for enhancing genome-wide coexpression dynamics study.
AB  - Statistical similarity analysis has been instrumental in elucidation of the
      voluminous microarray data. Genes with correlated expression profiles tend to be
      functionally associated. However, the majority of functionally associated genes
      turn out to be uncorrelated. One conceivable reason is that the expression of a
      gene can be sensitively dependent on the often-varying cellular state. The
      intrinsic state change has to be plastically accommodated by gene-regulatory
      mechanisms. To capture such dynamic coexpression between genes, a concept termed
      "liquid association" (LA) has been introduced recently. LA offers a scoring
      system to guide a genome-wide search for critical cellular players that may
      interfere with the coexpression of a pair of genes, thereby weakening their
      overall correlation. Although the LA method works in many cases, a direct
      extension to more than two genes is hindered by the "curse of dimensionality."
      Here we introduce a strategy of finding an informative 2D projection to
      generalize LA for multiple genes. A web site is constructed that performs on-line
      LA computation for any user-specified group of genes. We apply this scoring
      system to study yeast protein complexes by using the Saccharomyces cerevisiae
      protein complexes database of the Munich Information Center for Protein
      Sequences. Human genes are also investigated by profiling of 60 cancer cell lines
      of the National Cancer Institute. In particular, our system links the expression
      of the Alzheimer's disease hallmark gene APP (amyloid-beta precursor protein) to
      the beta-site-cleaving enzymes BACE and BACE2, the gamma-site-cleaving enzymes
      presenilin 1 and 2, apolipoprotein E, and other Alzheimer's disease-related
      genes.

PMID- 15492224
TI  - Dissociation of experience-dependent and -independent changes in excitatory
      synaptic transmission during development of barrel cortex.
AB  - A fundamental problem in the study of cortical development is the extent to which
      the formation and refinement of synaptic circuitry depends upon sensory
      experience. The barrel cortex is a useful model system to study experience
      dependent cortical development because there is a simple mapping of individual
      whiskers to the corresponding barrel columns in the cortex. We investigated
      experience-dependent and -independent changes in glutamatergic synaptic
      transmission in the barrel cortex during the second postnatal week by comparing
      synaptic responses from whisker-intact mice at postnatal day (P) 7 and P14 with
      those from whisker-deprived mice at P14. alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA)-receptor-mediated
      excitatory synaptic responses were recorded from layer 2/3 pyramidal cells in
      vitro during voltage-clamp in response to stimulation in layer 4. We observed
      that the ratio of synaptic AMPA- to NMDA-receptor-mediated current (A/N ratio)
      increased with developmental age. The development of the A/N ratio was unchanged
      by deprivation of the whisker input throughout the second postnatal week. In
      contrast, the NMDA-receptor current decay and sensitivity to the NMDA receptor 2B
      subunit-selective antagonist ifenprodil was affected strongly by such
      deprivation. These results demonstrate a concurrent dissociation between sensory
      experience-dependent and -independent changes of glutamatergic transmission in
      the barrel cortex during the second postnatal week. Furthermore, they suggest
      that the development of subunit composition of synaptic receptors is dependent on
      sensory experience, whereas maturation of the synaptic A/N ratio is independent
      of such experience. Thus, different components of synaptic development may be
      governed by different developmental rules.

PMID- 15492225
TI  - Role of a transductional-transcriptional processor complex involving MyD88 and
      IRF-7 in Toll-like receptor signaling.
AB  - Toll-like receptor (TLR) activation is central to immunity, wherein the
      activation of the TLR9 subfamily members TLR9 and TLR7 results in the robust
      induction of type I IFNs (IFN-alpha/beta) by means of the MyD88 adaptor protein.
      However, it remains unknown how the TLR signal "input" can be processed through
      MyD88 to "output" the induction of the IFN genes. Here, we demonstrate that the
      transcription factor IRF-7 interacts with MyD88 to form a complex in the
      cytoplasm. We provide evidence that this complex also involves IRAK4 and TRAF6
      and provides the foundation for the TLR9-dependent activation of the IFN genes.
      The complex defined in this study represents an example of how the coupling of
      the signaling adaptor and effector kinase molecules together with the
      transcription factor regulate the processing of an extracellular signal to evoke
      its versatile downstream transcriptional events in a cell. Thus, we propose that
      this molecular complex may function as a cytoplasmic transductional
      transcriptional processor.

PMID- 15492226
TI  - TIFA activates IkappaB kinase (IKK) by promoting oligomerization and
      ubiquitination of TRAF6.
AB  - TRAF6 (tumor necrosis factor receptor-associated factor 6) is a RING (really
      interesting new gene) domain ubiquitin (Ub) ligase that mediates the activation
      of protein kinases, such as transforming growth factor beta-activated kinase
      (TAK1) and IkappaB kinase (IKK), by catalyzing the formation of a unique
      polyubiquitin chain linked through Lys-63 of Ub. Here, we present evidence that
      TIFA (TRAF-interacting protein with a forkhead-associated domain, also known as
      T2BP) activates IKK by promoting the oligomerization and Ub ligase activity of
      TRAF6. We show that recombinant TIFA protein, but not TRAF6-binding-defective
      mutant, can activate IKK in crude cytosolic extracts. Furthermore, TIFA activates
      IKK in an in vitro reconstitution system consisting of purified proteins,
      including TRAF6, the TAK1 kinase complex, and Ub-conjugating enzyme complex Ubc13
      Uev1A. Interestingly, a fraction of recombinant TIFA protein exists as high
      molecular-weight oligomers, and only these oligomeric forms of TIFA can activate
      IKK. Importantly, TIFA induces the oligomerization and polyubiquitination of
      TRAF6, which leads to the activation of TAK1 and IKK through a proteasome
      independent mechanism.

PMID- 15492227
TI  - Multiarm spirals in a two-dimensional cardiac substrate.
AB  - A variety of chemical and biological nonlinear excitable media, including heart
      tissue, can support stable, self-organized waves of activity in a form of
      rotating single-arm spirals. In particular, heart tissue can support stationary
      and meandering spirals of electrical excitation, which have been shown to
      underlie different forms of cardiac arrhythmias. In contrast to single-arm
      spirals, stable multiarm spirals (multiple spiral waves that rotate in the same
      direction around a common organizing center) have not been demonstrated and
      studied yet in living excitable tissues. Here, we show that persistent multiarm
      spirals of electrical activity can be induced in monolayer cultures of neonatal
      rat heart cells by a short, rapid train of electrical point stimuli applied
      during single-arm-spiral activity. Stable formation is accomplished only in
      monolayers that show a relatively broad and steep dependence of impulse
      wavelength and propagation velocity on rate of excitation. The resulting multiarm
      spirals emit waves of electrical activity at rates faster than for single-arm
      spirals and exhibit two distinct behaviors, namely "arm-switching" and "tip
      switching." The phenomenon of rate acceleration due to an increase in the number
      of spiral arms possibly may underlie the acceleration of functional reentrant
      tachycardias paced by a clinician or an antitachycardia device.

PMID- 15492228
TI  - Clues to understanding cold sensation: thermodynamics and electrophysiological
      analysis of the cold receptor TRPM8.
AB  - The cold and menthol receptor, TRPM8, also designated CMR1, is a member of the
      transient receptor potential (TRP) family of excitatory ion channels. TRPM8 is a
      channel activated by cold temperatures, voltage, and menthol. In this study, we
      characterize the cold- and voltage-induced activation of TRPM8 channel in an
      attempt to identify the temperature- and voltage-dependent components involved in
      channel activation. Under equilibrium conditions, decreasing temperature has two
      effects. (i) It shifts the normalized conductance vs. voltage curves toward the
      left, along the voltage axis. This effect indicates that the degree of order is
      higher when the channel is in the open configuration. (ii) It increases the
      maximum channel open probability, suggesting that temperature affects both
      voltage-dependent and -independent pathways. In the temperature range between 18
      degrees C and 25 degrees C, large changes in enthalpy (DeltaH=-112 kcal/mol) and
      entropy (DeltaS=-384 cal/mol K) accompany the activation process. The Q10
      calculated in the same temperature range is 24. This thermodynamic analysis
      strongly suggests that the process of opening involves large conformational
      changes of the channel-forming protein. Therefore, the highly temperature
      dependent transition between open and closed configurations is possible because
      enthalpy and entropy are both large and compensate each other. Our data also
      demonstrate that temperature and voltage interact allosterically to enhance
      channel opening.

PMID- 15492229
TI  - Fusogenic supramolecular vesicle systems induced by metal ion binding to
      amphiphilic ligands.
AB  - The incorporation of lipophilic ligands into the bilayer membrane of vesicles
      offers the possibility to induce, upon binding of suitable metal ions, a variety
      of processes, in particular vesicle aggregation and fusion and generation of
      vesicle arrays, under the control of specific metal-ligand recognition events.
      Synthetic bipyridine lipoligands Bn bearing a bipyridine unit as head group were
      prepared and incorporated into large unilamellar vesicles. The addition of Ni2+
      or Co2+ metal ions led to the formation of complexes MBn and MBn2 followed by
      spontaneous fusion to generate giant multilamellar vesicles. The metal ion
      complexation was followed by UV spectroscopy and the progressive fusion could be
      visualized by optical dark-field and fluorescence microscopies. Vesicle fusion
      occurred without leakage of the aqueous compartments and resulted in the
      formation of multilamellar giant vesicles because of the stacking of the
      lipoligands Bn. The fusion process required a long enough oligoethylene glycol
      spacer and a minimal concentration of lipoligand within the vesicle membrane.
      Metallosupramolecular systems such as the present one offer an attractive way to
      induce selective intervesicular processes, such as vesicle fusion, under the
      control of molecular recognition between specific metal ions and lipoligands
      incorporated in the bilayer membrane. They provide an approach to the design of
      artificial "tissue-mimetics" through the generation of polyvesicular arrays of
      defined architecture and to the control of their functional properties.

PMID- 15492230
TI  - Inhibitor of apoptosis proteins: translating basic knowledge into clinical
      practice.
AB  - The inhibitor of apoptosis proteins (IAPs) are a family of antiapoptotic proteins
      that bind and inhibit caspases 3, 7, and/or 9, but not caspase 8. Growing
      evidence also indicates that IAPs also modulate cell division, cell cycle
      progression, and signal transduction pathways. As our basic understanding of IAPs
      has increased, the knowledge is being translated into clinically useful
      applications in the diagnosis and treatment of malignancy. For example, IAPs such
      as survivin are being investigated as diagnostic markers for the presence of
      occult malignancy. In addition, IAP overexpression is a poor prognostic marker in
      a variety of solid tumors and hematologic malignancies. Finally, IAPs are
      attractive therapeutic targets, and efforts are under way to develop antisense
      and chemical IAP inhibitors that may be useful for the treatment of a variety of
      malignancies. For all of these potential clinical applications, however, the
      challenge remains to incorporate these findings into actual clinical practice.

PMID- 15492232
TI  - The orphan nuclear receptor constitutive active/androstane receptor is essential
      for liver tumor promotion by phenobarbital in mice.
AB  - Hepatocellular carcinoma (HCC) is known to progress through a step often called
      tumor promotion. Phenobarbital (PB) is the prototype of nongenotoxic cacinogens
      that promote HCC in rodents. The molecular target of PB to elicit the promotion
      has been the subject of intense investigations over the last 30 years since it
      was discovered. The nuclear receptor constitutive active/androstane receptor
      (CAR) is activated by PB as well as by various other xenobiotics such as
      therapeutic drugs and environmental pollutants. CAR activation results in the
      transcriptional induction of numerous hepatic genes including those that encode
      xenobiotic-metabolizing enzymes such as a set of cytochrome P450s. In addition to
      PB, many CAR activators are nongenotoxic carcinogens, but the role of CAR in
      liver tumor promotion remains unexplored. Using Car(-/-) mice, we have here
      examined tumor promotion by chronic treatment with PB in drinking water after
      tumor initiation with a single dose of the genotoxic carcinogen
      diethylnitrosamine. None of the Car(-/-) mice developed either eosinophilic foci
      or advanced liver tumors, whereas all Car(+/+) mice developed HCC and/or adenoma
      by 39 weeks. The results indicate that CAR is the molecular target of promotion
      by PB and that activation of this receptor is an essential requirement for liver
      tumor development.

PMID- 15492231
TI  - The gap junction protein connexin32 is a mouse lung tumor suppressor.
AB  - Although loss of connexin expression and/or gap junction intercellular
      communication correlates with decreased growth control and increased neoplastic
      potential, there is limited evidence directly linking gap junction intercellular
      communication function with tumor suppression in situ. Here, we show for the
      first time that a gap junction protein, connexin32 (Cx32), acts as a lung tumor
      suppressor in a mouse model. Cx32-deficient nontumorous lung tissue exhibited an
      increased proliferative index (P < 0.001), and, after exposure to the carcinogen
      diethylnitrosamine, Cx32-deficient mice exhibited a highly statistically
      significant (P < 0.001) increase in bronchioloalveolar lung tumor incidence (28
      of 45, 62%) and a 45% increase in average multiplicity compared with wild-type
      mice (7 of 29, 24%). Tumors from Cx32-deficient mice also showed increased
      activation of mitogen-activated protein kinase (P < 0.001) compared with wild
      type tumors, implicating this signaling pathway in Cx32/gap junction
      intercellular communication-associated lung tumorigenesis.

PMID- 15492233
TI  - A gene expression signature associated with metastatic outcome in human
      leiomyosarcomas.
AB  - Metastasis is a major factor associated with poor prognosis in cancer, but little
      is known of its molecular mechanisms. Although the clinical behavior of soft
      tissue sarcomas is highly variable, few reliable determinants of outcome have
      been identified. New markers that predict clinical outcome, in particular the
      ability of primary tumors to develop metastatic tumors, are urgently needed.
      Here, we have chosen leiomyosarcoma as a model for examining the relationship
      between gene expression profile and the development of metastasis in soft tissue
      sarcomas. Using cDNA microarray, we have identified a gene expression signature
      associated with metastasis in sarcoma that allowed prediction of the future
      development of metastases of primary tumors (Kaplan-Meier analysis P = 0.001).
      Our finding may aid the tailoring of therapy for individual sarcoma patients,
      where the aggressiveness of treatment is affected by the predicted outcome of
      disease.

PMID- 15492234
TI  - Gene expression profiling in uveal melanoma reveals two molecular classes and
      predicts metastatic death.
AB  - Melanomas are notoriously difficult to classify because of a lack of discrete
      clinical and pathological stages. Here, we show that primary uveal melanomas
      surprisingly cluster into two distinct molecular classes based on gene expression
      profile. Genes that discriminate class 1 (low-grade) from class 2 (high-grade)
      include highly significant clusters of down-regulated genes on chromosome 3 and
      up-regulated genes on chromosome 8q, which is consistent with previous
      cytogenetic studies. A three-gene signature allows biopsy-size tumor samples to
      be assigned accurately to tumor classes using either array or PCR platforms. Most
      importantly, this molecular classification strongly predicts metastatic death and
      outperforms other clinical and pathological prognostic indicators. These studies
      offer new insights into melanoma pathogenesis, and they provide a practical
      foundation for effective clinical predictive testing.

PMID- 15492235
TI  - Cyclooxygenase-2 is expressed in neuroblastoma, and nonsteroidal anti
      inflammatory drugs induce apoptosis and inhibit tumor growth in vivo.
AB  - Neuroblastoma is the single most common and deadly tumor of childhood and is
      often associated with therapy resistance. Cyclooxygenases (COXs) catalyze the
      conversion of arachidonic acid to prostaglandins. COX-2 is up-regulated in
      several adult epithelial cancers and is linked to proliferation and resistance to
      apoptosis. We detected COX-2 expression in neuroblastoma primary tumors and cell
      lines but not in normal adrenal medullas from children. Treatment of
      neuroblastoma cells with nonsteroidal anti-inflammatory drugs, inhibitors of COX,
      induced caspase-dependent apoptosis via the intrinsic mitochondrial pathway.
      Treatment of established neuroblastoma xenografts in nude rats with the dual COX
      1/COX-2 inhibitor diclofenac or the COX-2-specific inhibitor celecoxib
      significantly inhibited tumor growth in vivo (P < 0.001). In vitro, arachidonic
      acid and diclofenac synergistically induced neuroblastoma cell death. This effect
      was further pronounced when lipooxygenases were simultaneously inhibited. Proton
      magnetic resonance spectroscopy ((1)H MRS) of neuroblastoma cells treated with
      COX inhibitors demonstrated accumulation of polyunsaturated fatty acids and
      depletion of choline compounds. Thus, (1)H MRS, which can be performed with
      clinical magnetic resonance scanners, is likely to provide pharmacodynamic
      markers of neuroblastoma response to COX inhibition. Taken together, these data
      suggest the use of nonsteroidal anti-inflammatory drugs as a novel adjuvant
      therapy for children with neuroblastoma.

PMID- 15492236
TI  - p53-Binding protein 1 is fused to the platelet-derived growth factor receptor
      beta in a patient with a t(5;15)(q33;q22) and an imatinib-responsive eosinophilic
      myeloproliferative disorder.
AB  - We describe the fusion of TP53BP1 to PDGFRB in a patient with a chronic myeloid
      leukemia-like disorder associated with eosinophilia and a t(5;15)(q33;q22).
      TP53BP1 encodes 53BP1, a p53-binding protein that plays a role in cellular
      responses to DNA damage. The 53BP1-PDGFRbeta fusion protein is predicted to
      retain the kinetochore-binding domain of 53BP1 fused to the transmembrane and
      intracellular tyrosine kinase domain of PDGFRbeta. The presence of the fusion was
      confirmed by two-color fluorescence in situ hybridization, reverse transcription
      PCR, and by characterizing the genomic breakpoints. The reciprocal fusion, which
      would contain the p53-binding 53BP1 BRCA1 COOH-terminal domains, was not
      detectable by fluorescence in situ hybridization or nested PCR. Imatinib, a known
      inhibitor of PDGFRbeta, blocked the growth of patient colony-forming unit,
      granulocyte-macrophage in vitro and produced a clinically significant response
      before relapse and subsequent death with imatinib-resistant disease. We conclude
      that TP53BP1-PDGFRB is a novel imatinib target in atypical chronic myeloid
      leukemia.

PMID- 15492237
TI  - Id2 drives differentiation and suppresses tumor formation in the intestinal
      epithelium.
AB  - Oncogenic signals elevate expression of Id2 in multiple tumor types. When
      deregulated, Id2 inactivates the tumor suppressor proteins retinoblastoma, p107,
      and p130. Here, we report a novel and unexpected tumor inhibitory function of Id2
      in the intestinal epithelium. First, genetic ablation of Id2 in the mouse
      prevents differentiation and cell cycle arrest of enterocytes at the time of
      formation of the crypt-villus unit. Later, these developmental abnormalities
      evolve toward neoplastic transformation with complete penetrance. Id2-null tumors
      contain severe dysplastic and metaplastic lesions and express aberrant amounts of
      beta-catenin. Thus, our data are the first to establish a direct requirement of
      basic helix-loop-helix inhibitors in driving differentiation and define an
      unexpected role for the retinoblastoma-binding protein Id2 in preventing tumor
      formation.

PMID- 15492238
TI  - COP1, the negative regulator of p53, is overexpressed in breast and ovarian
      adenocarcinomas.
AB  - The tumor suppressor protein p53 plays a central role in protecting normal cells
      from undergoing transformation. Thus, it is fitting that cancer cells selectively
      dampen the p53 response to gain a selective growth advantage. In fact, the p53
      gene is the most commonly mutated tumor suppressor gene in human cancers, and if
      the gene is not mutated, then other components of the p53 pathways are skewed to
      dampen the p53 response to stress. We recently identified COP1 as a novel and
      critical negative regulator of p53. COP1 is a RING finger-containing protein that
      targets p53 for degradation to the proteasome and is necessary for p53 turnover
      in normal and cancer cells. However, the association between COP1 and cancer
      remains to be determined. We performed expression analysis of COP1 in ovarian and
      breast cancer tissue microarrays. COP1 is significantly overexpressed in 81% (25
      of 32) of breast and 44% (76 of 171) of ovarian adenocarcinoma as assessed by in
      situ hybridization and immunohistochemistry. Overexpression of COP1 correlated
      with a striking decrease in steady state p53 protein levels and attenuation of
      the downstream target gene, p21, in cancers that retain a wild-type p53 gene
      status. Overall, these results suggest that overexpression of COP1 contributes to
      the accelerated degradation of p53 protein in cancers and attenuates the tumor
      suppressor function of p53.

PMID- 15492239
TI  - Combined total genome loss of heterozygosity scan of breast cancer stroma and
      epithelium reveals multiplicity of stromal targets.
AB  - Recent breast cancer studies have highlighted the importance of interactions
      between cancer epithelium and tumor stroma. Recently, the focus of solid tumor
      investigations has shifted from mutations in carcinomatous epithelium to
      disturbances of tissue organization in cancer. The genetic basis of this
      microenvironment, however, remains to be clarified. To begin to resolve this
      problem, a total genome loss of heterozygosity (LOH) scan was done on epithelial
      and stromal DNA from 134 sporadic invasive breast carcinomas. In addition to
      detecting more frequent LOH at three loci in stroma than in epithelium, we found
      strong evidence that LOH frequencies were significantly elevated in specific
      regions of each chromosome. We detected 57 markers, which were preferentially
      lost either in stroma (n = 38) or epithelium (n = 19), relative to the background
      LOH frequencies on their respective chromosomes. This multiplicity of stromal
      cell LOH, and hence loss of genetic material, provides a possible mechanism for
      interpatient variation in host-stromal response to invading adenocarcinoma cells.
      This is consistent with a model in which initial, random LOH occurs equally among
      epithelium and stroma, but subsequent clonal selection is driven by factors,
      which appear to be distinctly different between malignant epithelial and
      surrounding stromal cells. Genetic alterations in stroma did not mimic those in
      epithelium, but they could play a different and parallel role in carcinogenesis
      and tumor progression, probably by modifying some features specific to breast
      cancer.

PMID- 15492240
TI  - Cleavage of beta-catenin by calpain in prostate and mammary tumor cells.
AB  - Mutations in the NH(2)-terminal regulatory domain of the beta-catenin gene lead
      to aberrant stabilization and accumulation of the protein and increased TCF/LEF
      dependent transcription. Although these mutations are common in some cancers,
      they are infrequent in prostate and breast cancer. We have found that metastatic
      prostate cancer specimens, obtained through a rapid autopsy tissue procurement
      program, expressed a novel M(r) 75,000 proteolytic fragment of beta-catenin (beta
      cat(75)). beta-Cat(75) was also expressed in multiple prostate and breast cancer
      cell lines and was closely associated with the activity of the calcium-dependent
      protease, calpain. In a prostate cancer cDNA microarray, m-calpain RNA levels
      were found to be significantly increased in metastatic disease compared with
      normal prostate. We showed calpain-dependent generation of beta-cat(75) in cell
      culture and in vitro. Molecular mapping revealed that calpain cleavage removed
      the NH(2)-terminal regulatory domain of the beta-catenin protein. Treatment of
      MCF-7 cells with ionomycin led to increased accumulation of beta-cat(75) in the
      nucleus and TCF-dependent transcriptional activity. Overexpression of a similar
      beta-catenin fragment that lacks the NH(2)-terminal 132 amino acids and has
      transforming potential activated TCF-dependent transcription. Given the low
      frequency of mutation-induced activation of beta-catenin in prostate and breast
      cancers, proteolytic cleavage of beta-catenin by calpain may represent a novel
      mechanism by which the protein is activated during tumorigenesis.

PMID- 15492241
TI  - Gefitinib induces apoptosis in the EGFRL858R non-small-cell lung cancer cell line
      H3255.
AB  - Somatic mutations in the tyrosine kinase domain of the epidermal growth factor
      receptor (EGFR) have recently been described in patients with non-small-cell lung
      cancer (NSCLC) who achieve radiographic regressions to the EGFR inhibitor
      gefitinib. One of these mutations, L858R (Leu-->Arg), is also found in NSCLC cell
      line H3255, which is very sensitive to gefitinib treatment. We characterized nine
      NSCLC cell lines (three isolated from patients with bronchioloalveolar carcinoma
      and six isolated from patients with adenocarcinoma) for their in vitro
      sensitivity to gefitinib. Of these, only H3255 (EGFR(L858R)) and H1666 (EGFR(WT))
      are sensitive to gefitinib with IC(50) values of 40 nmol/L and 2 micromol/L,
      respectively. We examined the effects of gefitinib on H3255 and cell lines
      containing wild-type EGFR that are either sensitive (H1666) or resistant (A549
      and H441) to gefitinib exposure in vitro. Gefitinib treatment (1 micromol/L)
      leads to significant apoptosis accompanied by increased poly(ADP-ribose)
      polymerase cleavage only in the H3255 cell line, leads to G(1)-S arrest in H1666,
      and has no effects in the A549 and H441 cell lines. Although EGFR and AKT are
      constitutively phosphorylated in H3255, H1666, and H441 cell lines, AKT is
      completely inhibited by gefitinib treatment only in the H3255 cell line. These
      findings further characterize a mechanism by which gefitinib treatment of NSCLC
      harboring EGFR(L858R) leads to a dramatic response to gefitinib.

PMID- 15492242
TI  - NOD2 3020insC alone is not sufficient for colorectal cancer predisposition.
AB  - Mutations in NOD2 have been shown to associate with increased susceptibility to
      Crohn's disease. A recent Polish study linked the truncating NOD2 3020insC
      variant with an increased risk of colorectal cancer (CRC) at an older age (>50
      years) of disease onset, with an odds ratio of 2.23. We studied the possible
      contribution of the 3020insC variant to CRC risk in a series of 1,042 Finnish
      population-based patients from which 926 samples were successfully analyzed and
      in 348 anonymous cancer-free controls. The frequency of the 3020insC mutation was
      3.7% in both CRC patients (34 of 926, including 1 homozygote) and cancer-free
      controls (13 of 348; odds ratio, 0.98; confidence interval, 0.51-1.88). Contrary
      to the Polish study, there was no significant difference in the mutation rates
      between CRC patients > 50 years of age (25 of 576; 4.3%) and controls in the
      present series. We studied respective tumor tissue DNAs of all patients
      displaying heterozygous 3020insC changes for loss of heterozygosity. Loss of
      heterozygosity at NOD2 was observed in only 1 of the 33 CRC samples. Our results
      suggest that NOD2 3020insC alone does not contribute to CRC risk. If this variant
      predisposes to CRC, additional factors not present in the Finnish population need
      to be involved.

PMID- 15492243
TI  - The nuclear factor kappaB subunits RelA/p65 and c-Rel potentiate but are not
      required for Ras-induced cellular transformation.
AB  - Extensive data indicate that oncoproteins, such as oncogenic H-Ras, initiate
      signal transduction cascades that ultimately lead to the activation of specific
      transcription factors. We and others have previously demonstrated that Ras
      activates the inherent transcriptional activation function of the transcription
      factor nuclear factor kappaB (NF-kappaB). Supportive of the importance of NF
      kappaB in transformation, Ras-induced cellular transformation can be suppressed
      by expression of IkappaBalpha, an inhibitor of NF-kappaB, or by dominant-negative
      forms of the upstream activator IkappaB kinase (IKK). However, conclusive
      evidence for a requirement for NF-kappaB subunits in oncogenic transformation has
      not been reported. Furthermore, there is little understanding of the gene targets
      controlled by NF-kappaB that might support oncogenic conversion. The data
      presented here demonstrate that, although both p65 and c-Rel enhance the
      frequency of Ras-induced cellular transformation, these NF-kappaB subunits are
      not essential for Ras to transform spontaneously immortalized murine fibroblasts.
      Microarray analysis identified a set of genes induced by Ras that is dependent on
      NF-kappaB for their expression and that likely play contributory roles in
      promoting Ras-induced oncogenic transformation.

PMID- 15492244
TI  - Targeted expression of human MYCN selectively causes pancreatic neuroendocrine
      tumors in transgenic zebrafish.
AB  - The zebrafish model organism has been used extensively for studies of genetic
      pathways in development, indicating its potential applicability to cancer. Here
      we show that targeted expression of MYCN in cells of the pancreatic islet induces
      neuroendocrine carcinoma. Four transgenic fish developed abdominal tumors between
      4 and 6 months of age, and histologic analysis revealed lobulated arrangements of
      neoplastic cells with expression of the MYCN transgene. The tumors also expressed
      insulin mRNA, and pancreatic exocrine cells and ducts were identified within the
      neoplasms, indicating a pancreatic origin for the tumor. Transmission electron
      microscopy revealed cytoplasmic, endocrine-dense core granules, analogous to
      those found in human neuroendocrine tumors. Our studies establish a zebrafish
      transgenic model of pancreatic neuroendocrine carcinoma, setting the stage to
      evaluate molecular pathways downstream of MYCN in this vertebrate forward genetic
      model system.

PMID- 15492245
TI  - Distinct chromosomal bias of gene expression signatures in the progression of
      hepatocellular carcinoma.
AB  - To identify the chromosomal aberrations associated with the progression of liver
      cancer, we applied expression imbalance map analysis to gene expression data from
      31 hepatocellular carcinomas and 19 noncancerous tissues. Expression imbalance
      map analysis, which detects mRNA expression imbalance correlated with chromosomal
      regions, showed that expression gains of 1q21-23 (74%), 8q13-21 (48%), 12q23-24
      (41%), 17q12-21(48%), 17q25 (25%), and 20q11 (22%) and losses of 4q13 (48%), 8p12
      21 (32%), 13q14 (32%), and 17p13 (29%) were significantly associated with
      hepatocellular carcinoma. Most regions with altered expression identified by
      expression imbalance map were also identified in previous reports using
      comparative genomic hybridization. We demonstrated chromosomal copy number gain
      in 1q21-23 and loss in 17p13 by genomic quantitative PCR, suggesting that gene
      expression profiles reflect chromosomal alterations. Furthermore, expression
      imbalance map analysis revealed that more poorly differentiated hepatocellular
      carcinoma contain more chromosomal alterations, which are accumulated in a
      stepwise manner in the course of hepatocellular carcinoma progression: expression
      imbalance of 1q, 8p, 8q, and 17p occur as early events in hepatocarcinogenesis,
      and 12q, 17q25 and 20q occur as later events. In particular, expression gain of
      17q12-21 and loss of 4q were seen to accumulate constantly through the
      dedifferentiation process. Our data suggest that gene expression profiles are
      subject to chromosomal bias and that expression imbalance map can correlate gene
      expression to gene loci with high resolution and sensitivity.

PMID- 15492246
TI  - Role of human Ku86 in telomere length maintenance and telomere capping.
AB  - The role of Ku86 at telomeres has been extensively studied in various organisms;
      however, a role for Ku86 at human telomeres was unknown because Ku86 deletion is
      lethal for human cells. Here, we used small interference RNA to decrease Ku86
      protein levels in human cells. An approximately 50% reduction in the amount of
      Ku86 protein was achieved 72 hours after transfection with Ku86-specific small
      interference RNAs. This decrease in Ku86 levels resulted in a rapid loss of cell
      viability characterized by increased apoptosis and decreased mitotic index in the
      cell population. Importantly, Ku86 knockdown was concomitant with a significant
      loss of telomeric sequences and with increased chromosomal aberrations, including
      chromatid-type fusions involving telomeric sequences. These findings demonstrate
      a role for Ku86 in regulating telomere length and telomere capping in human
      cells, which, in turn, could impact on cancer and aging.

PMID- 15492247
TI  - Ontogeny and oncogenesis balance the transcriptional profile of renal cell
      cancer.
AB  - Global transcript analysis is increasingly used to describe cancer taxonomies
      beyond the microscopic reach of the eye. Diagnostic and prognostic portraits are
      formulated by ranking cancers according to transcriptional proximity. However,
      the role that distinct biological factors play in defining these portraits
      remains undefined. It is likely that the transcriptional repertoire of cancers
      depends, on one hand, on the anamnestic retention of their ontogenesis and, on
      the other, on the emergence of novel expression patterns related to oncogenesis.
      We compared the transcriptional profile of primary renal cell cancers (RCCs) with
      that of normal kidney tissue and several epithelial cancers of nonrenal origin to
      weigh the contribution that ontogeny and oncogenesis make in molding their
      genetic profile. Unsupervised global transcript analysis demonstrated that RCCs
      retain transcriptional signatures related to their ontogeny and cluster close to
      normal renal epithelium. When renal lineage-associated genes are removed from the
      analysis and cancer-specific genes are analyzed, RCCs segregate with other
      cancers with limited lineage specificity underlying a predominance of the
      oncogenic process over lineage specificity. However, a RCC-specific set of
      oncogenesis-related genes was identified and surprisingly shared by sarcomas. In
      summary, the transcriptional portrait of primary RCCs is largely dominated by
      ontogeny. Genes responsible for lineage specificity may represent poor molecular
      targets for immune or drug therapy. Most genes associated with oncogenesis are
      shared with other cancers and may represent better therapeutic targets. Finally,
      a small subset of genes is associated with lineage-specific oncogenesis, and
      these may provide information regarding the biological behavior of RCCs and
      facilitate diagnostic classification of RCCs.

PMID- 15492248
TI  - The Ews/Fli-1 fusion gene changes the status of p53 in neuroblastoma tumor cell
      lines.
AB  - One hallmark of Ewing's sarcoma/peripheral neuroectodermal tumors is the presence
      of the Ews/Fli-1 chimeric oncogene. Interestingly, infection of neuroblastoma
      tumor cell lines with Ews/Fli-1 switches the differentiation program of
      neuroblastomas to Ewing's sarcoma/peripheral neuroectodermal tumors. Here we
      examined the status of cytoplasmically sequestered wt-p53 in neuroblastomas after
      stable expression of Ews/Fli-1. Immunofluorescence revealed that in the
      neuroblastoma-Ews/Fli-1 infectant cell lines, p53 went from a punctate-pattern of
      cytoplasmic sequestration to increased nuclear localization. Western blot
      analysis revealed that PARC was down-regulated in one neuroblastoma cell line but
      not expressed in the second. Therefore, decreased PARC expression could not fully
      account for relieving p53 sequestration in the neuroblastoma tumor cells.
      Neuroblastoma-Ews/Fli-1 infectant cell lines showed marked increases in p53
      protein expression without transcriptional up-regulation. Interestingly, p53 was
      primarily phosphorylated, without activation of its downstream target p21(WAF1).
      Western blot analysis revealed that whereas MDM2 gene expression does not change,
      p14(ARF), a negative protein regulator of MDM2, increases. These observations
      suggest that the downstream p53 pathway may be inactivated as a result of
      abnormal p53. We also found that p53 has an extended half-life in the
      neuroblastoma-Ews/Fli-1 infectants despite the retention of a wild-type sequence
      in neuroblastoma-Ews/Fli-1 infectant cell lines. We then tested the p53 response
      pathway and observed that the neuroblastoma parent cells responded to genotoxic
      stress, whereas the neuroblastoma-Ews/Fli-1 infectants did not. These results
      suggest that Ews/Fli-1 can directly abrogate the p53 pathway to promote
      tumorigenesis. These studies also provide additional insight into the
      relationship among the p53 pathway proteins.

PMID- 15492249
TI  - Id2 is dispensable for myc-induced lymphomagenesis.
AB  - The Emu-Myc transgenic mouse appears to be an accurate model of human Burkitt's
      lymphoma that bears MYC/Immunoglobulin gene translocations. Id2, a negative
      regulator of basic helix-loop-helix transcription factors, has also been proposed
      as a Myc target gene that drives the proliferative response of Myc by binding to
      and overriding the checkpoint functions of the retinoblastoma tumor suppressor
      protein. Targeted deletion of Id2 in mice results in defects in B-cell
      development and prevents the development of peripheral lymphoid nodes. In
      precancerous B cells and lymphomas that arise in Emu-Myc transgenic mice and in
      Burkitt's lymphomas, Id2 is overexpressed, suggesting that it plays a regulatory
      role in lymphoma development. Surprisingly, despite these connections, Emu-Myc
      mice lacking Id2 succumb to lethal B-cell lymphoma at rates comparable with wild
      type Emu-Myc transgenics. Furthermore, precancerous splenic B cells lacking Id2
      do not exhibit any significant defects in Myc-induced target gene transactivation
      and proliferation. However, due to their lack of secondary lymph nodes, Emu-Myc
      mice lacking Id2 rather succumb to disseminated lymphoma with an associated
      leukemia, with pronounced infiltrates of the bone marrow and other major organs.
      Collectively these findings argue that targeting Id2 functions may be ineffective
      in preventing Myc-associated malignancies.

PMID- 15492250
TI  - Identification of hypoxia-regulated proteins in head and neck cancer by proteomic
      and tissue array profiling.
AB  - Hypoxia within solid tumors decreases therapeutic efficacy, and identification of
      hypoxia markers may influence the choice of therapeutic modality. Here, we used a
      proteomic approach to identify hypoxia-regulated proteins and validated their use
      as endogenous indicators of tumor hypoxia. Using two-dimensional gel
      electrophoresis and PowerBlot (antibody-based array), we identified a group of 20
      proteins that are increased >/=1.5-fold during hypoxia. The majority of these
      proteins such as IkappaB kinase beta (IKKbeta), MKK3b, highly expressed in cancer
      (HEC), density-regulated protein 1, P150(glued), nuclear transport factor 2,
      binder of ARL 2, Paxillin, and transcription termination factor I have not been
      previously reported to be hypoxia inducible. The increase in these proteins under
      hypoxia was mediated through posttranscriptional mechanisms. We additionally
      characterized the role of IKKbeta, a regulator of the nuclear factor-kappaB
      transcription factor, during hypoxia. We demonstrated that IKKbeta mediates cell
      survival during hypoxia and is induced in a variety of squamous cell carcinoma
      cell lines. Furthermore, we showed that IKKbeta expression from tumor specimens
      correlated with tumor oxygenation in patients with head and neck squamous cell
      carcinomas. These data suggest that IKKbeta is a novel endogenous marker of tumor
      hypoxia and may represent a new target for anticancer therapy.

PMID- 15492251
TI  - Signal pathways in up-regulation of chemokines by tyrosine kinase MER/NYK in
      prostate cancer cells.
AB  - The AXL/UFO family of tyrosine kinases is characterized by a common N-CAM (neural
      adhesion molecule)-related extracellular domain and a common ligand, GAS6 (growth
      arrest-specific protein 6). Family members are prone to transcriptional
      regulation and carry out diverse functions including the regulation of cell
      adhesion, migration, phagocytosis, and survival. In this report, we describe a
      new role of MER/N-CAM-related kinase (NYK), a member of the AXL family of
      kinases, in the up-regulation of chemokines in prostate cancer cells. We show
      that NYK has elevated expression in a subset of tumor specimens and prostate
      cancer cell lines. Activation of NYK in the prostate cancer cell line DU145 does
      not cause a mitogenic effect; instead, it causes a differentiation phenotype.
      Microarray analysis revealed that NYK is a strong inducer of endocrine factors
      including interleukin (IL)-8 and several other angiogenic CXC chemokines as well
      as bone morphogenic factors. The dramatic increase of IL-8 expression is seen at
      both transcriptional and posttranscriptional levels. The downstream signals
      engaged by NYK were characterized, and those responsible for the up-regulation of
      IL-8 transcription were defined. In contrast to IL-1alpha, NYK-induced up
      regulation of IL-8 in DU145 depends on the mitogen-activated protein kinase
      kinase/extracellular signal-regulated kinase/Jun/Fos pathway, but not
      phosphoinositide 3'-kinase/nuclear factor-kappaB. These data define a new
      function of the AXL family of kinases and suggest a potential role of NYK in
      prostate cancer progression.

PMID- 15492252
TI  - DNA damage, repair, and mutation induction by (+)-Syn and (-)-anti
      dibenzo[a,l]pyrene-11,12-diol-13,14-epoxides in mouse cells.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental carcinogens.
      PAHs are classified into bay and fjord region compounds according to structural
      differences in the molecule region where enzymatic epoxidation occurs.
      Dibenzo[a,l]pyrene (DB[a,l]P), one of the fjord region compounds, has been
      demonstrated to be the most carcinogenic PAH known to date. DB[a,l]P is activated
      to fjord region (+)-syn and (-)-anti-11,12-dihydroxy-13,14-epoxy-11,12,13,14
      tetrahydrodibenzo[a,l]pyrene (DB[a,l]PDE) metabolites. In this study, we analyzed
      mutagenesis induced by (+)-syn- and (-)-anti-DB[a,l]PDE at the cII transgene in
      Big-Blue mouse cells. The mutant frequency of untreated cells (background level)
      was 6.53 x 10(-5). This level increased 3.7-fold for 20 nmol/L, 5.3-fold for 50
      nmol/L, and 7.9-fold for 100 nmol/L (+)-syn-DB[a,l]PDE, respectively. In the case
      of (-)-anti-DB[a,l]PDE it increased 4.5-fold for 20 nmol/L, 6.7-fold for 50
      nmol/L, and 10.6-fold for 100 nmol/L, respectively, indicating that (-)-anti
      DB[a,l]PDE is slightly more mutagenic than (+)-syn-DB[a,l]PDE. The mutational
      spectra of (+)-syn- and (-)-anti-DB[a,l]PDE were quite similar except for several
      hotspots, specific for either (+)-syn-DB[a,l]PDE or (-)-anti-DB[a,l]PDE. The most
      frequently induced mutations were A to T transversions, which were 43.9% for (+)
      syn- and 38.8% for (-)-anti-DB[a,l]PDE. In addition, G to T transversions were
      induced significantly, at frequencies of 18.5% by (+)-syn- and 18.1% by (-)-anti
      DB[a,l]PDE. Using UvrABC cleavage and ligation-mediated PCR or the terminal
      transferase-dependent PCR method, we have determined DB[a,l]PDE-DNA adduct
      formation sites and repair rates in carcinogen-exposed cells. The mutation
      hotspots coincided with sites of strong adduct formation, but not all of the
      adduct hotspots were mutational hotspots. Slow adduct removal occurred for both
      (+)-syn- and (-)-anti-DB[a,l]PDE adducts over a time period of up to 72 hours.
      The data suggest that, although the (-)-anti-isomer is slightly more mutagenic,
      DNA adducts of both DB[a,l]PDE stereoisomers may have similar biological
      properties. We discuss the implications of these findings for human cancer
      mutagenesis.

PMID- 15492253
TI  - Preneoplastic markers of hepatitis B virus-associated hepatocellular carcinoma.
AB  - Hepatitis B virus (HBV) carriers are at high risk for the development of
      hepatocellular carcinoma (HCC), but there are no reliable markers that will
      identify such high-risk carriers. The objective of this work is to identify
      serologic markers that may indicate the early presence of HCC. Since HBV-encoded
      X antigen (HBxAg) likely contributes to HCC by up- or down-regulation of host
      gene expression, X positive and negative HepG2 cells were made and subjected to
      cDNA subtraction. When specific ELISAs were constructed measuring differentially
      expressed antigens and corresponding antibodies, antibodies to several
      differentially expressed genes were detected. In cross-sectional and longitudinal
      studies, antibodies were predominantly present in patients with HBV-associated
      cirrhosis and HCC, but not in most carriers with hepatic inflammation alone or
      without active liver disease. Antibodies were also present in patients with
      hepatitis C virus (HCV)-related HCC, but rarely detected in sera from uninfected
      individuals, those with tumors other than HCC, or those with drug-induced
      hepatitis. Statistical analysis showed that HCC patients with four or more
      antibodies detectable before the appearance of HCC had decreased survival,
      suggesting that these markers may reflect stepwise hepatocarcinogenesis. Hence,
      these antibodies may serve as preneoplastic markers for HCC in HBV carriers with
      chronic liver disease, and may be identified by a simple blood test.

PMID- 15492254
TI  - Green fluorescent protein tagging of extracellular signal-regulated kinase and
      p38 pathways reveals novel dynamics of pathway activation during primary and
      metastatic growth.
AB  - We describe a novel approach that allows detection of primary and metastatic
      cells in vivo in which either the extracellular signal-regulated kinase (ERK) or
      the p38 pathway is activated. Our recent findings showed that ERK and p38 kinases
      regulate, respectively, programs dictating cell proliferation (high ERK-to-p38
      ratio) or growth arrest and dormancy (low ERK-to-p38 ratio) in vivo. Thus, we
      were able to use green fluorescent protein (GFP) to reflect ERK and p38
      activities and, consequently, the proliferative state of cancer cells. This was
      accomplished by transfecting tumorigenic T-HEp3 and HT1080 cells, and dormant D
      HEp3 cells, with plasmids coding for Elk-GAL4 or CHOP-GAL4 fusion proteins that,
      when phosphorylated by either ERK or p38, respectively, transactivated a GFP
      reporter gene. The fate of these cells was examined in culture, in primary sites,
      and in spontaneous metastasis in chick embryos and nude mice. In culture GFP
      level was directly proportional to the previously established levels of ERK or
      p38 activation. In contrast, during the first 24 hours of in vivo inoculation,
      both the tumorigenic and the dormant cells strongly activated the p38 pathway.
      However, in the tumorigenic cells, p38 activity was rapidly silenced, correcting
      the ERK/p38 imbalance and contributing to high ERK activity throughout the entire
      period of tumor growth. In contrast, in the small nodules formed by dormant
      cells, the level of ERK activity was dramatically reduced, whereas p38 activity
      remained high. Strong activation of ERK was evident in metastatic sites, whereas
      p38 activation was silenced in this anatomic location as well. These results show
      that it is possible to directly measure cancer cell response to microenvironment
      with this reporter system and that only proliferation-competent cells have the
      ability to rapidly adapt ERK and p38 signaling for proliferative success. This
      approach allows isolation and further characterization of metastatic cells with
      specific signaling signatures indicative of their phenotypes.

PMID- 15492255
TI  - Progressive loss of Syk and abnormal proliferation in breast cancer cells.
AB  - The tumor suppressor gene Syk tyrosine kinase is absent or reduced in invasive
      breast cancer tissues and cell lines; its loss in breast tissues is linked to
      poor prognosis and metastasis. Also, evidence shows that in vitro Syk is involved
      in regulating proliferation. Here, we show by in situ hybridization on breast
      tissue sections that the loss of Syk expression is progressive during tumor
      development. Strikingly, Syk is already partially lost in normal epithelial
      tissue adjacent to the cancer lesion. In vivo, cell proliferation (as measured by
      the proliferative index Ki67) increased from normal to ductal carcinoma in situ
      to invasive, whereas Syk in situ staining in the same tissues decreased. In
      vitro, the presence of Syk was associated with reduced cell proliferation in an
      epidermal growth factor receptor-overexpressing breast cancer cell line, BT549,
      whereas changes in apoptosis were undetected. Concomitantly, the kinase activity
      of the proto-oncogene Src was reduced by approximately 30%. A 5-fold increase in
      abnormal mitoses was observed in the Syk-transfected cells compared with vector
      control. We propose that Syk is involved in the regulation of cell proliferation,
      possibly by controlling mechanisms of mitosis and cytokinesis via Src signal
      transduction pathway(s). Because of its progressive and early loss during tumor
      onset and development, monitoring of Syk loss in breast epithelial cells by
      noninvasive techniques such as ductal lavage may be a powerful tool for screening
      purposes.

PMID- 15492256
TI  - Restoration of bone morphogenetic protein receptor type II expression leads to a
      decreased rate of tumor growth in bladder transitional cell carcinoma cell line
      TSU-Pr1.
AB  - Bone morphogenetic proteins (BMPs), potential regulators of cellular growth and
      metastasis that signal through an interaction with plasma membrane receptors,
      have been suggested to be important regulators of malignant cells. The present
      study was carried out to evaluate the potential role of BMP receptor (BMP-R)
      types IA, IB, and II in bladder transitional cell carcinoma (TCC) cells.
      Initially, we investigated the expression of these BMP-Rs in 30 archival tissues
      of human bladder TCC using immunohistochemistry; 10 benign bladder specimens were
      used for comparison. The results demonstrated that the expression of BMP-Rs is
      localized preferentially to the transitional epithelium and that there was a
      significant association between loss of BMP-RII expression and tumor grade. To
      find a cell line that can serve as a model system for clinical observation, we
      subsequently examined sensitivity to BMP-4 and expression of BMP-RII, BMP-RIA,
      and BMP-RIB in three human bladder cancer cell lines, TCC-Sup, RT4, and TSU-Pr1.
      Of the three cell lines, TSU-Pr1 exhibited a decreased level of BMP-RII
      expression and was resistant to the growth-inhibitory effect of BMP-4.
      Overexpression of BMP-RII in TSU-Pr1 cells not only restored BMP-4 responsiveness
      but also significantly decreased tumorigenicity in vivo. Taken together, these
      results demonstrate that human bladder TCC tissues have a frequent loss of BMP
      RII expression and that overexpression of BMP-RII leads to restoration of BMP
      signaling and decreased tumor growth in the human bladder TCC cell line TSU-Pr1.

PMID- 15492257
TI  - Up-regulation of Flotillin-2 is associated with melanoma progression and
      modulates expression of the thrombin receptor protease activated receptor 1.
AB  - Flotillin 2 (flot-2) is a highly conserved protein isolated from caveolae/lipid
      raft domains that tether growth factor receptors linked to signal transduction
      pathways. Flot-2 protein and mRNA were increased in tumorigenic and metastatic
      melanoma cell lines in vitro, and the immunostaining intensity increased
      substantially across a tissue array of melanocytic lesions. Flot-2 transfection
      transformed SB2 melanoma cells from nontumorigenic, nonmetastatic to highly
      tumorigenic and metastatic in a nude mouse xenograft model. SB2 cells stably
      transfected with the flot-2 cDNA (SB2-flot)-2 cells proliferated faster in the
      absence of serum, and their migration through Matrigel was additionally enhanced
      by thrombin. When SB2-flot-2 cells were compared with SB2-vector-control cells on
      a cancer gene pathway array, SB2-flot-2 cells had increased expression of
      protease activated receptor 1 (PAR-1) mRNA, a transmembrane, G-protein-coupled
      receptor involved in melanoma progression. PAR-1 and flot-2 were
      coimmunoprecipitated from SB2-flot-2 cells. Up-regulation of PAR-1 was
      additionally confirmed in SB2-flot-2 cells and melanoma cell lines. SB2-flot-2
      cells transfected with flot-2-specific small-interfering RNAs made substantially
      less flot-2 and PAR-1 mRNA. In conclusion, flot-2 overexpression is associated
      with melanoma progression, with increased PAR-1 expression, and with
      transformation of SB2 melanoma cells to a highly metastatic line. Flot-2 binds to
      PAR-1, a known upstream mediator of major signal transduction pathways implicated
      in cell growth and metastasis, and may thereby influence tumor progression.

PMID- 15492258
TI  - The centrosomal kinase Nek2 displays elevated levels of protein expression in
      human breast cancer.
AB  - Aneuploidy and chromosome instability are common abnormalities in human cancer.
      Loss of control over mitotic progression, multipolar spindle formation, and
      cytokinesis defects are all likely to contribute to these phenotypes. Nek2 is a
      cell cycle-regulated protein kinase with maximal activity at the onset of mitosis
      that localizes to the centrosome. Functional studies have implicated Nek2 in
      regulation of centrosome separation and spindle formation. Here, we present the
      first study of the protein expression levels of the Nek2 kinase in human cancer
      cell lines and primary tumors. Nek2 protein is elevated 2- to 5-fold in cell
      lines derived from a range of human tumors including those of cervical, ovarian,
      breast, prostate, and leukemic origin. Most importantly, by immunohistochemistry,
      we find that Nek2 protein is significantly up-regulated in preinvasive in situ
      ductal carcinomas of the breast as well as in invasive breast carcinomas.
      Finally, by ectopic expression of Nek2A in immortalized HBL100 breast epithelial
      cells, we show that increased Nek2 protein leads to accumulation of
      multinucleated cells with supernumerary centrosomes. These data highlight the
      Nek2 kinase as novel potential target for chemotherapeutic intervention in breast
      cancer.

PMID- 15492259
TI  - Growth promoting signaling by tenascin-C [corrected].
AB  - Tenascin-C is an adhesion-modulating extracellular matrix molecule that is highly
      expressed in tumor stroma and stimulates tumor cell proliferation. Adhesion of
      T98G glioblastoma cells to a fibronectin substratum is inhibited by tenascin-C.
      To address the mechanism of action, we performed a RNA expression analysis of
      T89G cells grown in the presence or absence of tenascin-C and found that tenascin
      C down-regulates tropomyosin-1. Upon overexpression of tropomyosin-1, cell
      spreading on a fibronectin/tenascin-C substratum was restored, indicating that
      tenascin-C destabilizes actin stress fibers through down-regulation of
      tropomyosin-1. Tenascin-C also increased the expression of the endothelin
      receptor type A and stimulated the corresponding mitogen-activated protein kinase
      signaling pathway, which triggers extracellular signal-regulated kinase 1/2
      phosphorylation and c-Fos expression. Tenascin-C additionally caused down
      regulation of the Wnt inhibitor Dickkopf 1. In consequence, Wnt signaling was
      enhanced through stabilization of beta-catenin and stimulated the expression of
      the beta-catenin target Id2. Finally, our in vivo data derived from astrocytoma
      tissue arrays link increased tenascin-C and Id2 expression with high malignancy.
      Because increased endothelin and Wnt signaling, as well as reduced tropomyosin-1
      expression, are closely linked to transformation and tumorigenesis, we suggest
      that tenascin-C specifically modulates these signaling pathways to enhance
      proliferation of glioma cells.

PMID- 15492260
TI  - Apoptosis protease activator protein-1 expression is dispensable for response of
      human melanoma cells to distinct proapoptotic agents.
AB  - Loss of expression of the apoptosis protease activator protein-1 (APAF-1) in
      human melanoma is thought to promote resistance to programmed cell death by
      preventing caspase-9 activation. However, the role of the APAF-1-dependent
      pathway in apoptosis activated by cellular stress and/or DNA damage has been
      recently questioned. We investigated APAF-1 expression in a large panel of human
      melanomas and assessed cellular response to several proapoptotic agents in tumors
      expressing or lacking APAF-1 protein. In two melanomas with wild-type p53 but
      with differential expression of APAF-1, treatment with camptothecin, celecoxib,
      or an nitric oxide synthase inhibitor (1400W) significantly modulated expression
      of 36 of 96 genes in an apoptosis-specific cDNA macroarray, but APAF-1 mRNA
      levels were not induced (in APAF-1(-) cells) nor up-regulated (in APAF-1(+)
      cells), a finding confirmed at the protein level. Treatment with cisplatin,
      camptothecin, etoposide, betulinic acid, celecoxib, 1400W, and staurosporine
      promoted enzymatic activity not only of caspases -2, -8, and -3 but also of
      caspase-9 in both APAF-1(+) and APAF-1(-) tumor cells. Moreover, drug-induced
      caspase-9 enzymatic activity could be not only partially but significantly
      reduced by caspase-2, -3, and -8 -specific inhibitors in both APAF-1(+) and APAF
      1(-) tumor cells. In response to 1 to 100 micromol/L of cisplatin, camptothecin,
      or celecoxib, APAF-1(+) melanomas (n = 12) did not show significantly increased
      levels of apoptosis compared with APAF-1(-) tumors (n = 7), with the exception of
      enhanced apoptosis in response to a very high dose (100 micromol/L) of etoposide.
      These results suggest that the response of human melanoma cells to different
      proapoptotic agents may be independent of their APAF-1 phenotype.

PMID- 15492261
TI  - Adhesion-independent alpha6beta4 integrin clustering is mediated by
      phosphatidylinositol 3-kinase.
AB  - Clustering of cell-surface integrins is known to augment integrin-mediated signal
      transduction, but mechanisms of integrin clustering are poorly understood. Here
      we report that adhesion-independent clustering of alpha6beta4 integrin, known to
      be important in mediating tumor cell motility, is driven by phosphatidylinositol
      3-kinase (PI3K) but does not require activation of the PI3K-Akt pathway. We
      observed clustering of alpha6beta4 in breast carcinoma cells after adhesion
      independent cross-linking of the beta4 integrin subunit. Clustering was
      significantly blocked when cross-linking was performed in the presence of PI3K
      inhibitors LY294002 and wortmannin. In contrast, no significant inhibition of
      clustering was observed with protein kinase C inhibitor GF109203X, rapamycin, or
      heparin. Although alpha6beta4 clustering was blocked by PI3K inhibitors,
      clustering was not associated with increased PI3K lipid kinase activity or
      increased phosphorylation of Akt. A novel role for PI3K in alpha6beta4 integrin
      clustering is proposed.

PMID- 15492262
TI  - PAX5 expression in acute leukemias: higher B-lineage specificity than CD79a and
      selective association with t(8;21)-acute myelogenous leukemia.
AB  - The transcription factor PAX5 plays a key role in the commitment of hematopoietic
      precursors to the B-cell lineage, but its expression in acute leukemias has not
      been thoroughly investigated. Hereby, we analyzed routine biopsies from 360 acute
      leukemias of lymphoid (ALLs) and myeloid (AMLs) origin with a specific anti-PAX5
      monoclonal antibody. Blasts from 150 B-cell ALLs showed strong PAX5 nuclear
      expression, paralleling that of CD79a in the cytoplasm. Conversely, PAX5 was not
      detected in 50 T-cell ALLs, including 20 cases aberrantly coexpressing CD79a.
      Among 160 cytogenetically/molecularly characterized AMLs, PAX5 was selectively
      detected in 15 of 42 cases bearing the t(8;21)/AML1-ETO rearrangement. Real-time
      reverse transcription-PCR studies in t(8;21)-AML showed a similar up-regulation
      of PAX5 transcript in all of the 8 tested samples (including 4 cases that were
      negative at anti-PAX5 immunostaining), suggesting that PAX5 is expressed in
      t(8;21)-AML more widely than shown by immunohistochemistry. Interestingly,
      PAX5(+) t(8;21)-AML also expressed CD79a and/or CD19 (major transcriptional
      targets of PAX5 in B-cells) in 10 of 12 evaluable cases. Our results indicate
      that PAX5 is a more specific marker than CD79a for B-cell ALL diagnosis.
      Moreover, among AMLs, PAX5 expression selectively clusters with t(8;21), allowing
      its immunohistochemical recognition in a proportion of cases, and likely
      explaining a peculiar biological feature of this subset of myeloid leukemias,
      i.e. the aberrant expression of B-cell genes.

PMID- 15492263
TI  - Gene expression of parathyroid tumors: molecular subclassification and
      identification of the potential malignant phenotype.
AB  - Parathyroid tumors are heterogeneous, and diagnosis is often difficult using
      histologic and clinical features. We have undertaken expression profiling of 53
      hereditary and sporadic parathyroid tumors to better define the molecular
      genetics of parathyroid tumors. A class discovery approach identified three
      distinct groups: (1) predominantly hyperplasia cluster, (2) HRPT2/carcinoma
      cluster consisting of sporadic carcinomas and benign and malignant tumors from
      Hyperparathyroidism-Jaw Tumor Syndrome patients, and (3) adenoma cluster
      consisting mainly of primary adenoma and MEN 1 tumors. Gene sets able to
      distinguish between the groups were identified and may serve as diagnostic
      biomarkers. We demonstrated, by both gene and protein expression, that Histone 1
      Family 2, amyloid beta precursor protein, and E-cadherin are useful markers for
      parathyroid carcinoma and suggest that the presence of a HRPT2 mutation, whether
      germ-line or somatic, strongly influences the expression pattern of these 3
      genes. Cluster 2, characterized by HRPT2 mutations, was the most striking,
      suggesting that parathyroid tumors with somatic HRPT2 mutation or tumors
      developing on a background of germ-line HRPT2 mutation follow pathways distinct
      from those involved in mutant MEN 1-related parathyroid tumors. Furthermore, our
      findings likely preclude an adenoma to carcinoma progression model for
      parathyroid tumorigenesis outside of the presence of either a germ-line or
      somatic HRPT2 mutation. These findings provide insights into the molecular
      pathways involved in parathyroid tumorigenesis and will contribute to a better
      understanding, diagnosis, and treatment of parathyroid tumors.

PMID- 15492264
TI  - Clusterin-mediated apoptosis is regulated by adenomatous polyposis coli and is
      p21 dependent but p53 independent.
AB  - Clusterin is a widely expressed glycoprotein that has been paradoxically observed
      to have both pro- and antiapoptotic functions. Recent reports suggest this
      apparent dichotomy of function may be related to two different isoforms, one
      secreted and cytoplasmic, the other nuclear. To clarify the functional role of
      clusterin in regulating apoptosis, we examined its expression in human colon
      cancer tissues and in human colon cancer cell lines. We additionally explored its
      expression and activity using models of adenomatous polyposis coli (APC)- and
      chemotherapy-induced apoptosis. Clusterin RNA and protein levels were decreased
      in colon cancer tissues largely devoid of wild-type APC when compared with
      matched normal tissue controls, suggesting a means for invasive cancers to avoid
      apoptosis. Conversely, induction of apoptosis by expression of wild-type APC or
      by treatment with chemotherapy led to increased clusterin RNA and protein levels
      localizing to apoptotic nuclei. We found that transient transfection of clusterin
      to colon cancer cell lines directly enhanced basal and chemotherapy-induced
      apoptosis. Clusterin-induced apoptosis was inhibited by antisense clusterin and
      was found to be highly dependent on p21 but not p53 expression, yet a deficit in
      p21 can be subverted by clusterin transfection. Collectively, these data support
      the hypothesis that nuclear clusterin function is proapoptotic when induced by
      APC or chemotherapy in the context of p21 expression. Absent of p21, clusterin in
      not induced, and apoptosis is significantly inhibited. These data support a
      potential therapeutic role for clusterin in enhancing chemotherapy-induced
      apoptosis and in promoting apoptosis in cells deficient in p21.

PMID- 15492265
TI  - Neuroblastoma angiogenesis is inhibited with a folded synthetic molecule
      corresponding to the epidermal growth factor-like module of the follistatin
      domain of SPARC.
AB  - Secreted protein acidic and rich in cysteine (SPARC) is a multifunctional
      matricellular glycoprotein. In vitro, SPARC inhibits the proliferation and
      migration of endothelial cells stimulated by growth factors and induces
      endothelial cell apoptosis. We previously showed that SPARC also inhibits
      angiogenesis in vivo and impairs the growth of the pediatric tumor neuroblastoma
      (NB). SPARC comprises three domains that are independently folded by a complex
      pattern of disulfide bonds and have a high degree of structural conservation. In
      this study, separate modules of the SPARC domains were synthesized as cysteine
      linked peptides and tested for their ability to inhibit angiogenesis. Peptide FS
      E, representing the epidermal growth factor (EGF)-like module of the follistatin
      (FS) domain, did not cause endothelial cell apoptosis but strongly inhibited
      basic fibroblast growth factor (bFGF)-induced endothelial cell migration with an
      ED(50) = 10 pmol/L. In vivo, peptide FS-E blocked bFGF-stimulated angiogenesis
      and neovascularization induced by NB cells. The EGF-like conformation was
      essential for peptide FS-E function because reduction of its two disulfide bonds
      completely abrogated peptide activity. Peptides FS-K and EC-N, corresponding to
      part of the Kazal module of the FS domain and the conserved alpha-helix in the
      extracellular calcium-binding domain, respectively, had minimal to no inhibitory
      activity. Our data show that the EGF-like module of the SPARC FS domain is
      angiosuppressive, and its structural conformation is critical for antiangiogenic
      activity.

PMID- 15492266
TI  - HIV-1 protease inhibitor, ritonavir: a potent inhibitor of CYP3A4, enhanced the
      anticancer effects of docetaxel in androgen-independent prostate cancer cells in
      vitro and in vivo.
AB  - We previously showed that HIV-1 protease inhibitors (PIs) slowed the
      proliferation of human myeloid leukemia cells and enhanced their differentiation
      in the presence of all-trans-retinoic acid. In this study, we found that PIs,
      including ritonavir, saquinavir, and indinavir, inhibited the growth of DU145 and
      PC-3 androgen-independent prostate cancer cells as measured by a clonal
      proliferation assay. Recent studies showed that ritonavir inhibited cytochrome
      P450 3A4 enzyme (CYP3A4) in liver microsomes. The CYP3A4 is involved in drug
      metabolism and acquisition of drug resistance. To clarify the drug interaction
      between ritonavir and other anticancer drugs, we cultured DU145 cells with
      docetaxel either alone or in combination with ritonavir. Ritonavir enhanced the
      antiproliferative and proapoptotic effects of docetaxel in the hormonally
      independent DU145 prostate cancer cells in vitro as measured by the clonogenic
      soft agar assay and detection of the activated form of caspase-3 and cleavage of
      poly(ADP-ribose) polymerase using Western blot analysis. Real-time PCR showed
      that docetaxel induced the expression of CYP3A4 at the transcriptional level, and
      ritonavir (10(-5) mol/L) completely blocked this induction. An ELISA-based assay
      also showed that ritonavir inhibited DNA binding activity of nuclear factor
      kappaB (NFkappaB) in DU145 cells, which is a contributor to drug resistance in
      cancer cells. Furthermore, combination treatment of docetaxel and ritonavir
      dramatically inhibited the growth of DU145 cells present as tumor xenografts in
      BNX nude mice compared with either drug alone. Importantly, docetaxel induced
      expression of CYP3A4 in DU145 xenografts, and ritonavir completely blocked this
      induction. Ritonavir also inhibited NFkappaB DNA binding activity in DU145
      xenografts. Extensive histologic analyses of the liver, spleen, kidneys, bone
      marrow, skin, and subcutaneous fat pads from these mice showed no abnormalities.
      In summary, combination therapy of ritonavir and anticancer drugs holds promise
      for the treatment of individuals with advanced, drug resistant cancers.

PMID- 15492267
TI  - Spermine acts as a negative regulator of macrophage differentiation in human
      myeloid leukemia cells.
AB  - The role of putrescine, spermidine and spermine in phorbol 12-myristate-13
      acetate (PMA)-induced macrophage differentiation was examined in human HL-60 and
      U-937 myeloid leukemia cells. Unlike other polyamines, spermine affected this
      differentiation by acting as a negative regulator. This negative regulation was
      established by showing that the PMA-induced macrophage phenotype, but not PMA
      associated replication arrest, was abrogated (a) by replenishing the PMA-evoked
      decrease in cellular spermine levels with this polyamine from an exogenous source
      and (b) by blocking PMA-induced expression of the polyamine catabolic enzyme N(1)
      spermidine/spermine acetyltransferase (SSAT) with antisense oligonucleotides in
      the presence of low substrate level. The PMA-evoked reduction in cellular
      spermine appears to result from an increase in the activity of SSAT and a
      decrease in the activity of ornithine decarboxylase, the polyamine biosynthetic
      enzyme. To a degree, these changes are due to corresponding changes in the
      expression of the genes that code for these enzymes. When cell differentiation is
      initiated, SSAT expression is increased after PMA-evoked activation of protein
      kinase C-beta. The present studies raise the possibility that agents able to
      reduce spermine levels in patients' myeloid leukemia cells may enhance the
      activity of differentiation therapy drugs for this type of leukemia.

PMID- 15492268
TI  - Prostaglandin E2 enhances pancreatic cancer invasiveness through an Ets-1
      dependent induction of matrix metalloproteinase-2.
AB  - Accumulating evidence suggests an important role for cyclooxygenase-2 (COX-2) in
      the pathogenesis of a wide range of malignancies. Here we tested the hypothesis
      that the COX-2 product prostaglandin E(2) (PGE(2)) increases cellular invasive
      potential by inducing matrix metalloproteinase-2 (MMP-2) expression and activity
      through an extracellular signal-regulated kinase (ERK)/Ets-1-dependent mechanism
      in pancreatic cancer. PANC-1 and MIAPaCa-2 pancreatic cancer cells were treated
      with PGE(2) or rofecoxib, a selective COX-2 inhibitor. MMP-2 expression and
      activity were assayed using Western blot analysis and zymography, respectively.
      MMP-2 promoter activity was analyzed with a luciferase-based assay. Ets-1
      activity was analyzed using gel shift assay. Ets-1 expression was specifically
      silenced using RNA interference. Cellular invasive and migratory potentials were
      determined using a Boyden chamber assay with or without Matrigel, respectively.
      Exogenous PGE(2) induced MMP-2 expression and activity and increased ERK1/2
      phosphorylation, Ets-1 binding activity, and MMP-2 promoter activity. PGE(2) also
      increased cellular migratory and invasive potentials. The mitogen-activated
      protein kinase kinase inhibitor PD98059 and Ets-1 silencing each abolished PGE(2)
      induced increases in MMP-2 expression. PD98059 and Ets-1 silencing each abrogated
      the effect of PGE(2) on cellular invasive potential but not on cellular migratory
      potential. Rofecoxib suppressed MMP-2 expression and activity, Ets-1 binding
      activity, MMP-2 promoter activity, and cellular migratory and invasive
      potentials. These results suggest that PGE(2) mediates pancreatic cancer cellular
      invasiveness through an ERK/Ets-1-dependent induction of MMP-2 expression and
      activity. They also suggest that COX-2 inhibition may represent a strategy to
      inhibit invasive potential in pancreatic cancer.

PMID- 15492269
TI  - Modulation of gene expression by tumor-derived p53 mutants.
AB  - p53 mutants with a single amino acid substitution are overexpressed in a majority
      of human cancers containing a p53 mutation. Overexpression of the mutant protein
      suggests that there is a selection pressure on the cell indicative of an active
      functional role for mutant p53. Indeed, H1299 cells expressing mutant p53-R175H,
      p53-R273H or p53-D281G grow at a faster rate compared with a control cell line.
      Using p53-specific small interfering RNA, we show that the growth rate of mutant
      p53-expressing cells decreases as mutant p53 level decreases, demonstrating that
      the increased cellular growth is dependent on p53 expression. Increased growth
      rate is not observed for H1299 cell clones expressing mutant p53-D281G
      (L22Q/W23S), which has been shown to be defective in transactivation in transient
      transcriptional assays. This shows that the increased growth rate imparted by
      mutant p53 in H1299 cells requires the transactivation function of mutant p53. By
      performing microarray hybridization analyses, we show that constitutive
      expression of three common p53 mutants (p53-R175H, p53-R273H, and p53-D281G) in
      H1299 human lung carcinoma cells evokes regulation of a common set of genes, a
      significant number of which are involved in cell growth regulation. Predictably,
      H1299 cells expressing p53-D281G (L22Q/W23S) are defective in up-regulating a
      number of these genes. The differences in expression profiles induced by
      individual p53 mutants in the cells may be representative of the p53 mutants and
      how they can affect gene expression resulting in the observed "gain of function"
      phenotypes (i.e., increased growth rate, decreased sensitivity to
      chemotherapeutic agents, and so forth).

PMID- 15492270
TI  - The palmitoylation of metastasis suppressor KAI1/CD82 is important for its
      motility- and invasiveness-inhibitory activity.
AB  - The cancer metastasis suppressor protein KAI1/CD82 is a member of the tetraspanin
      superfamily. Recent studies have demonstrated that tetraspanins are palmitoylated
      and that palmitoylation contributes to the organization of tetraspanin webs or
      tetraspanin-enriched microdomains. However, the effect of palmitoylation on
      tetraspanin-mediated cellular functions remains obscure. In this study, we found
      that tetraspanin KAI1/CD82 was palmitoylated when expressed in PC3 metastatic
      prostate cancer cells and that palmitoylation involved all of the cytoplasmic
      cysteine residues proximal to the plasma membrane. Notably, the palmitoylation
      deficient KAI1/CD82 mutant largely reversed the wild-type KAI1/CD82's inhibitory
      effects on migration and invasion of PC3 cells. Also, palmitoylation regulates
      the subcellular distribution of KAI1/CD82 and its association with other
      tetraspanins, suggesting that the localized interaction of KAI1/CD82 with
      tetraspanin webs or tetraspanin-enriched microdomains is important for
      KAI1/CD82's motility-inhibitory activity. Moreover, we found that KAI1/CD82
      palmitoylation affected motility-related subcellular events such as lamellipodia
      formation and actin cytoskeleton organization and that the alteration of these
      processes likely contributes to KAI1/CD82's inhibition of motility. Finally, the
      reversal of cell motility seen in the palmitoylation-deficient KAI1/CD82 mutant
      correlates with regaining of p130(CAS)-CrkII coupling, a signaling step important
      for KAI1/CD82's activity. Taken together, our results indicate that
      palmitoylation is crucial for the functional integrity of tetraspanin KAI1/CD82
      during the suppression of cancer cell migration and invasion.

PMID- 15492271
TI  - Invasive potential induced under long-term oxidative stress in mammary epithelial
      cells.
AB  - Although the causal relationship between chronic inflammation and carcinogenesis
      has long been discussed, the molecular basis of the relation is poorly
      understood. In the present study, we focused on reactive oxygen species (ROS) and
      their signals under inflammatory conditions leading to the carcinogenesis of
      epithelial cells and found that repeated treatment with a low dose of H(2)O(2)
      (0.2 mmol/L) for periods of 2 to 4 days caused a phenotypic conversion of mouse
      NMuMG mammary epithelial cells from epithelial to fibroblast-like as in malignant
      transformation. The phenotypic conversion included the dissolution of cell-cell
      contacts, redistribution of E-cadherin in the cytoplasm, and up-regulation of a
      set of integrin family members (integrin alpha2, alpha6, and beta3) and matrix
      metalloproteinases (MMPs; MMP-3, -10, and -13), as analyzed using Northern blot
      analysis and quantitative reverse transcription-PCR. Gelatin zymography indicated
      post-transcriptional activation of gelatinases, including MMP-2 and -9. In
      parallel, p38 mitogen-activated protein kinase and extracellular signal-regulated
      kinase 1/2 were activated, which contributed to the induction of MMP-13, and a
      glutathione S-transferase pull-down assay showed the activation of a small
      GTPase, Rac1. Surprisingly, the prolonged oxidative treatment was sufficient to
      induce all of the aforementioned events. Most importantly, depending on the MMP
      activities, the epithelial cells exposed to oxidative conditions eventually
      acquired invasiveness in a reconstituted model system with a Matrigel invasion
      chamber containing normal fibroblasts at the bottom, providing the first
      substantial evidence supporting the direct role of ROS signals in the malignant
      transformation of epithelial cells.

PMID- 15492272
TI  - Human polynucleotide phosphorylase (hPNPaseold-35): a potential link between
      aging and inflammation.
AB  - Chronic inflammation is a characteristic feature of aging, and the relationship
      between cellular senescence and inflammation, although extensively studied, is
      not well understood. An overlapping pathway screen identified human
      polynucleotide phosphorylase (hPNPase(old-35)), an evolutionary conserved 3',5'
      exoribonuclease, as a gene up-regulated during both terminal differentiation and
      cellular senescence. Enhanced expression of hPNPase(old-35) via a replication
      incompetent adenovirus (Ad.hPNPase(old-35)) in human melanoma cells and normal
      human melanocytes results in a characteristic senescence-like phenotype. Reactive
      oxygen species (ROS) play a key role in the induction of both in vitro and in
      vivo senescence. We now document that overexpression of hPNPase(old-35) results
      in increased production of ROS, leading to activation of the nuclear factor (NF)
      kappaB pathway. Ad.hPNPase(old-35) infection promotes degradation of IkappaBalpha
      and nuclear translocation of NF-kappaB and markedly increases binding of the
      transcriptional activator p50/p65. The generation of ROS and activation of NF
      kappaB by hPNPase(old-35) are prevented by treatment with a cell-permeable
      antioxidant, N-acetyl-l-cysteine. Infection with Ad.hPNPase(old-35) enhances the
      production of interleukin (IL)-6 and IL-8, two classical NF-kappaB-responsive
      cytokines, and this induction is inhibited by N-acetyl-l-cysteine. A cytokine
      array reveals that Ad.hPNPase(old-35) infection specifically induces the
      expression of proinflammatory cytokines, such as IL-6, IL-8, RANTES, and matrix
      metalloproteinase (MMP)-3. We hypothesize that hPNPase(old-35) might play a
      significant role in producing pathological changes associated with aging by
      generating proinflammatory cytokines via ROS and NF-kappaB. Understanding the
      relationship between hPNPase(old-35) and inflammation and aging provides a unique
      opportunity to mechanistically comprehend and potentially intervene in these
      physiologically important processes.

PMID- 15492273
TI  - Selective activation of insulin receptor substrate-1 and -2 in pleural
      mesothelioma cells: association with distinct malignant phenotypes.
AB  - Molecular mechanisms active in transforming human pleural cells remain
      incompletely understood. Our previous microarray analysis of malignant pleural
      mesothelioma revealed alterations in components of the insulin-like growth factor
      (IGF) system, implicating this signaling axis in tumorigenesis. Therefore, in
      this current study, we characterized the molecular phenotype and investigated the
      key signaling pathways of the IGF system in malignant pleural mesothelioma
      specimens. For the major IGF components, we assessed mRNA abundance and total
      protein levels. We measured IGF-I ligand-dependent activation of signaling
      pathways downstream of the type I IGF receptor in a subset of malignant pleural
      mesothelioma cell lines and determined the corresponding biological consequences.
      At the transcriptional level, we observed consistent changes in IGF components
      that may contribute to a malignant phenotype. IGF-I stimulation of cells resulted
      in enhanced activation of type I IGF receptor and IRS adaptor proteins.
      Differential activation of IRS-1 signaling was associated with cell growth,
      whereas IRS-2 signaling was associated with cell motility. Thus, these data
      suggest that multiple mechanisms likely contribute to malignant pleural
      mesothelioma tumorigenesis. Therefore, IGF system components represent novel
      malignant pleural mesothelioma therapeutic targets for investigation.

PMID- 15492274
TI  - Adeno-associated viral vector-mediated expression of endostatin inhibits tumor
      growth and metastasis in an orthotropic pancreatic cancer model in hamsters.
AB  - We examined the feasibility of using adeno-associated virus (AAV)-mediated
      systemic delivery of endostatin in gene therapy to treat metastasis of pancreatic
      cancer. We established an animal model of orthotopic metastatic pancreatic cancer
      in which the pancreatic cancer cell line PGHAM-1 was inoculated into the pancreas
      of Syrian golden hamsters. Transplanted cells proliferated rapidly and
      metastasized to the liver. An AAV vector expressing endostatin (5 x 10(10)
      particles) was injected intramuscularly into the left quadriceps or intravenously
      into the portal vein. These routes of vector administration were evaluated by
      comparing various parameters of tumor development. Intramuscular injection of the
      vector modestly increased the serum endostatin level. The numbers of metastases
      and the incidence of hemorrhagic ascites were decreased in the treated animals.
      In contrast, the serum concentration of endostatin was significantly increased
      after intraportal injection of the vector. The antitumor effects on all
      parameters (including the size and microvessel density of primary pancreatic
      tumors, the sizes and number of liver metastases, and the incidence of
      hemorrhagic ascites) were significant. These results suggest that systemic
      delivery of endostatin represents a potentially effective treatment for
      pancreatic cancer and liver metastases. The route of vector administration
      influences the efficacy of AAV-mediated endostatin expression. Intraportal
      injection of the AAV vector appears to be more effective as an antiangiogenic
      gene therapy for pancreatic cancer.

PMID- 15492275
TI  - Gefitinib enhances the antitumor activity and oral bioavailability of irinotecan
      in mice.
AB  - As a single agent the ERBB1 inhibitor, gefitinib (Iressa; ZD1839) showed minimal
      activity against a panel of 10 pediatric tumor xenografts that do not express the
      ERBB1 receptor. However, combined with irinotecan (CPT-11), significantly greater
      than additive activity was observed in four of eight models (P < 0.05), and the
      combination showed enhanced activity against three additional tumor lines. Breast
      cancer resistance protein (ABCG2), a transporter that confers resistance to SN-38
      (the active metabolite of irinotecan), was readily detected in six of nine
      xenograft models examined by immunohistochemistry. In vitro gefitinib potently
      reversed resistance to SN-38 only in a cell line that overexpressed functional
      ABCG2. However, overexpression of ABCG2 did not decrease accumulation nor
      increase the rate of efflux of [(14)C]gefitinib. On the basis of these results
      and the distribution of Abcg2 in mouse tissues, we assessed the ability of
      gefitinib to modulate irinotecan pharmacokinetics. Oral gefitinib
      coadministration resulted in no change in clearance of intravenously administered
      irinotecan. However, gefitinib treatment dramatically increased the oral
      bioavailability of irinotecan after simultaneous oral administration. It is
      concluded that gefitinib may modulate SN-38 activity at the cellular level to
      reverse tumor resistance mediated by ABCG2 through inhibiting drug efflux and may
      be used potentially in humans to modulate the oral bioavailability of a poorly
      absorbed camptothecin such as irinotecan.

PMID- 15492276
TI  - Caveolin-1 is required for vascular endothelial growth factor-triggered multiple
      myeloma cell migration and is targeted by bortezomib.
AB  - We recently demonstrated that caveolae, vesicular flask-shaped invaginations of
      the plasma membrane, represent novel therapeutic targets in multiple myeloma. In
      the present study, we demonstrate that vascular endothelial growth factor (VEGF)
      triggers Src-dependent phosphorylation of caveolin-1, which is required for
      p130(Cas) phosphorylation and multiple myeloma cell migration. Conversely,
      depletion of caveolin-1 by antisense methodology abrogates p130(Cas)
      phosphorylation and VEGF-triggered multiple myeloma cell migration. The
      proteasome inhibitor bortezomib both inhibited VEGF-triggered caveolin-1
      phosphorylation and markedly decreased caveolin-1 expression. Consequently,
      bortezomib inhibited VEGF-induced multiple myeloma cell migration. Bortezomib
      also decreased VEGF secretion in the bone marrow microenvironment and inhibited
      VEGF-triggered tyrosine phosphorylation of caveolin-1, migration, and survival in
      human umbilical vascular endothelial cells. Taken together, these studies
      demonstrate the requirement of caveolae for VEGF-triggered multiple myeloma cell
      migration and identify caveolin-1 in multiple myeloma cells and human umbilical
      vascular endothelial cells as a molecular target of bortezomib.

PMID- 15492277
TI  - Antiangiogenic properties of fibstatin, an extracellular FGF-2-binding
      polypeptide.
AB  - By using the two-hybrid system with basic fibroblast growth factor (FGF-2) as
      bait, we isolated and characterized fibstatin, an endogenous M(r) 29,000 human
      basement membrane-derived inhibitor of angiogenesis and tumor growth. Fibstatin,
      a fragment containing the type III domains 12-14 of fibronectin, was produced as
      a recombinant protein and was shown to inhibit the proliferation, migration, and
      differentiation of endothelial cells in vitro. Antiangiogenic activity of
      fibstatin was confirmed in a Matrigel angiogenesis assay in vivo, and
      electrotransfer of the fibstatin gene into muscle tissue resulted in reduced
      B16F10 tumor growth. Taken together, these results suggest that fibstatin could
      act as a powerful molecule for antiangiogenic therapy.

PMID- 15492278
TI  - Modulation of gene expression in human central nervous system tumors under
      methionine deprivation-induced stress.
AB  - Methionine deprivation imposes a metabolic stress, termed methionine stress, that
      inhibits mitosis and induces cell cycle arrest and apoptosis. The methionine
      dependent central nervous system tumor cell lines DAOY (medulloblastoma), SWB61
      (anaplastic oligodendroglioma), SWB40 (anaplastic astrocytoma), and SWB39
      (glioblastoma multiforme) were compared with methionine-stress resistant SWB77
      (glioblastoma multiforme). The cDNA-oligoarray analysis and reverse transcription
      PCR verification indicated common changes in gene expression in methionine
      dependent cell lines to include up-regulation/induction of cyclin D1, mitotic
      arrest deficient (MAD)1, p21, growth arrest and DNA-damage-inducible (GADD)45
      alpha, GADD45 gamma, GADD34, breast cancer (BRCA)1, 14-3-3sigma, B-cell
      CLL/lymphoma (BCL)1, transforming growth factor (TGF)-beta, TGF-beta-induced
      early response (TIEG), SMAD5, SMAD7, SMAD2, insulin-like growth factor binding
      protein (IGFBP7), IGF-R2, vascular endothelial growth factor (VEGF), TNF-related
      apoptosis-inducing ligand (TRAIL), TNF-alpha converting enzyme (TACE), TRAIL
      receptor (TRAIL-R)2, TNFR-related death receptor (DR)6, TRAF interacting protein
      (I-TRAF), IL-6, MDA7, IL-1B convertase (ICE)-gamma, delta and epsilon, IRF1,
      IRF5, IRF7, interferon (IFN)-gamma and receptor components, ISG15, p65-NF-kappaB,
      JUN-B, positive cofactor (PC)4, C/ERB-beta, inositol triphosphate receptor I, and
      methionine adenosyltransferase II. On the other hand, cyclins A1, A2, B1 and B2,
      cell division cycle (CDC)2 and its kinase, CDC25 A and B, budding uninhibited by
      benzimidazoles (BUB)1 and 3, MAD2, CDC28 protein kinase (CKS)1 and 2,
      neuroepithelial cell transforming gene (NET)1, activator of S-phase kinase (ASK),
      CDC14B phosphatase, BCL2, TGF-beta activated kinase (TAK)1, TAB1, c-FOS, DNA
      topoisomerase II, DNA polymerase alpha, dihydrofolate reductase, thymidine
      kinase, stathmin, and MAP4 were down-regulated. In the methionine stress
      resistant SWB77, only 20% of the above genes were affected, and then only to a
      lesser extent. In addition, some of the changes observed in SWB77 were opposite
      to those seen in methionine-dependent tumors, including expression of p21, TRAIL
      R2, and TIEG. Despite similarities, differences between methionine-dependent
      tumors were substantial, especially in regard to regulation of cytokine
      expression. Western blot analysis confirmed that methionine stress caused the
      following: (a) a marked increase of GADD45alpha and gamma in the wt-p53 cell
      lines SWB61 and 40; (b) an increase in GADD34 and p21 protein in all of the
      methionine-dependent lines; and (c) the induction of MDA7 and phospho-p38 in DAOY
      and SWB39, consistent with marked transcriptional activation of the former under
      methionine stress. It was additionally shown that methionine stress down
      regulated the highly active phosphatidylinositol 3'-kinase pathway by reducing
      AKT phosphorylation, especially in DAOY and SWB77, and also reduced the levels of
      retinoblastoma (Rb) and pRb (P-ser780, P-ser795, and P-ser807/811), resulting in
      a shift in favor of unphosphorylated species in all of the methionine-dependent
      lines. Immunohistochemical analysis showed marked inhibition of nuclear
      translocation of nuclear factor kappaB under methionine stress in methionine
      dependent lines. In this study we show for the first time that methionine stress
      mobilizes several defined cell cycle checkpoints and proapoptotic pathways while
      coordinately inhibiting prosurvival mechanisms in central nervous system tumors.
      It is clear that methionine stress-induced cytotoxicity is not restricted by the
      p53 mutational status.

PMID- 15492279
TI  - Blockade of paclitaxel-induced thymidine phosphorylase expression can accelerate
      apoptosis in human prostate cancer cells.
AB  - Recently, survival benefit by chemotherapy using paclitaxel (PTX) and the
      induction of thymidine phosphorylase (TP) by PTX have been reported in several
      solid tumors. On the other hand, TP confers antiapoptotic effect on tumor cells
      through inhibition of caspase-8 activation in vitro. On the basis of these
      previous observations, we hypothesized that (a) TP can be induced after PTX
      treatment in human prostate cancer (PC) and (b) blockade of PTX-induced TP
      expression can enhance the apoptotic processes in human PC cells. PTX was used to
      find TP expression in all eight hormone-refractory PC cases after chemotherapy;
      however, cleaved caspase-8 was not expressed after chemotherapy in the six
      hormone-refractory PC cases with strong TP expression. In PC cell lines (PC-3, DU
      145, and LNCaP), TP expression after PTX treatment was clearly up-regulated in a
      dose-dependent manner. Cell viability of PC cell lines treated with PTX and TP
      antisense was significantly reduced in a time-dependent and dose-dependent manner
      compared with the PTX treatment alone. Likewise, apoptotic index of PC cells
      treated with PTX and TP antisense was significantly increased in comparison with
      PTX alone. After complete blockade of PTX-induced TP translation by TP antisense
      transfection, cleaved form of caspase-3 and poly(ADP-ribose) polymerase was
      increased, and this exaggeration of apoptosis also ran parallel with caspase-8
      activation in a PTX dose-dependent manner. However, in PC cell lines treated with
      TP antisense alone, neither caspase-3 nor poly(ADP-ribose) polymerase was cleaved
      despite caspase-8 activation. These results indicate that PTX-induced TP up
      regulation is associated with decreased caspase-8 activation. This study is the
      first report showing that blockade of PTX-induced TP expression could exaggerate
      the processing of apoptosis in PC cells treated with PTX. Our results provide
      preclinical evidence that TP could be a new molecular target for enhancing the
      potency of PTX-mediated apoptosis in PC cells.

PMID- 15492280
TI  - Gonadotropin-releasing hormone (GnRH) antagonists promote proapoptotic signaling
      in peripheral reproductive tumor cells by activating a Galphai-coupling state of
      the type I GnRH receptor.
AB  - Gonadotropin-releasing hormone (GnRH) receptor agonists are extensively used in
      the treatment of sex hormone-dependent cancers via the desensitization of
      pituitary gonadotropes and consequent decrease in steroid sex hormone secretion.
      However, evidence now points to a direct inhibitory effect of GnRH analogs on
      cancer cells. These effects appear to be mediated via the Galpha(i)-type G
      protein, in contrast to the predominant Galpha(q) coupling in gonadotropes.
      Unlike Galpha(q) coupling, Galpha(i) coupling of the GnRH receptor can be
      activated by both agonists and antagonists. This unusual pharmacology suggested
      that the receptor involved in the cancer cells may not be the classical
      gonadotrope type I GnRH receptor. However, we have previously shown that a
      functional type II GnRH receptor is not present in man. In the present study, we
      show that GnRH agonists and selective GnRH antagonists exert potent
      antiproliferative effects on JEG-3 choriocarcinoma, benign prostate hyperplasia
      (BPH-1), and HEK293 cells stably expressing the type I GnRH receptor. This
      antiproliferative action occurs through a Galpha(i)-mediated activation of stress
      activated protein kinase pathways, resulting in caspase activation and
      transmembrane transfer of phosphatidlyserine to the outer membrane envelope.
      Structurally related antagonistic GnRH analogs displayed divergent
      antiproliferative efficacies but demonstrated equal efficacies in inhibiting GnRH
      induced Galpha(q)-based signaling. Therefore the ability of GnRH receptor
      antagonists to exert an antiproliferative effect on reproductive tumors may be
      dependent on ligand-selective activation of the Galpha(i)-coupled form of the
      type I GnRH receptor.

PMID- 15492281
TI  - Inhibition of smoothened signaling prevents ultraviolet B-induced basal cell
      carcinomas through regulation of Fas expression and apoptosis.
AB  - Abnormal activation of the hedgehog-signaling pathway is the pivotal abnormality
      driving the growth of basal cell carcinomas (BCCs), the most common type of human
      cancer. Antagonists of this pathway such as cyclopamine may therefore be useful
      for treatment of basal cell carcinomas and other hedgehog-driven tumors. We
      report here that chronic oral administration of cyclopamine dramatically reduces
      ( approximately 66%) UVB induced basal cell carcinoma formation in Ptch1(+/-)
      mice. Fas expression is low in human and murine basal cell carcinomas but is up
      regulated in the presence of the smoothened (SMO) antagonist, cyclopamine, both
      in vitro in the mouse basal cell carcinoma cell line ASZ001 and in vivo after
      acute treatment of mice with basal cell carcinomas. This parallels an elevated
      rate of apoptosis. Conversely, expression of activated SMO in C3H10T1/2 cells
      inhibits Fas expression. Fas/Fas ligand interactions are necessary for
      cyclopamine-mediated apoptosis in these cells, a process involving caspase-8
      activation. Our data provide strong evidence that cyclopamine and perhaps other
      SMO antagonists are potent in vivo inhibitors of UVB-induced basal cell
      carcinomas in Ptch1(+/-) mice and likely in humans because the majority of human
      basal cell carcinomas manifest mutations in PTCH1 and that a major mechanism of
      their inhibitory effect is through up-regulation of Fas, which augments
      apoptosis.

PMID- 15492282
TI  - Treatment-induced changes in tumor oxygenation predict photodynamic therapy
      outcome.
AB  - Photodynamic therapy (PDT) requires oxygen to cause tumor damage, yet therapy
      itself can deplete or enhance tumor oxygenation. In the present work we measured
      the PDT-induced change in tumor oxygenation and explored its utility for
      predicting long-term response to treatment. The tissue hemoglobin oxygen
      saturation (SO(2)) of murine tumors was noninvasively measured by broadband
      diffuse reflectance spectroscopy. In initial validation studies, the
      oxyhemoglobin dissociation curve for mouse blood was accurately recreated based
      on measurements during deoxygenation of a tissue phantom of mouse erythrocytes.
      In vivo studies exhibited excellent correlation between carbogen-induced changes
      in SO(2) and pO(2) of radiation-induced fibrosarcoma tumors measured by
      reflectance spectroscopy and the Eppendorf pO(2) histograph, respectively. In PDT
      studies radiation-induced fibrosarcoma tumor SO(2) was measured immediately
      before and after Photofrin-PDT (135 J/cm(2), 38 mW/cm(2)). Animals were
      subsequently followed for tumor growth to a volume of 400 mm(3) (time-to-400
      mm(3)) or the presence of tumor cure (no tumor growth at 90 days after
      treatment). In animals that recurred, the PDT-induced change in tumor SO(2),
      i.e., relative-SO(2) (SO(2) after PDT/SO(2) before PDT) was positively correlated
      with treatment durability (time-to-400 mm(3)). The predictive value of relative
      SO(2) was confirmed in a second group of animals with enhanced pre-PDT
      oxygenation due to carbogen breathing. Furthermore, when all of the animals were
      considered (those that recurred and those that were cured) a highly significant
      association was found between increasing relative-SO(2) and increasing
      probability of survival, i.e., absence of recurrence. As independent variables,
      the SO(2) after PDT, the pre-PDT tumor volume, and light penetration depth all
      failed to predict response. As an independent variable, the SO(2) before PDT
      demonstrated a weak negative association with treatment durability; this
      association was driven by a correlation between decreasing pre-PDT SO(2) and
      increasing relative-SO(2). These data suggest that monitoring of PDT-induced
      changes in tumor oxygenation may be a valuable prognostic indicator.

PMID- 15492283
TI  - Fluoxetine inhibits multidrug resistance extrusion pumps and enhances responses
      to chemotherapy in syngeneic and in human xenograft mouse tumor models.
AB  - Multidrug resistance (MDR) operated by extrusion pumps such as P-glycoprotein and
      multidrug-resistance-associated-proteins, is a major reason for poor responses
      and failures in cancer chemotherapy. MDR modulators (chemosensitizers) were found
      among drugs approved for noncancer indications and their derivatives. Yet
      toxicity, adverse effects, and poor solubility at doses required for MDR reversal
      prevent their clinical application. Among newly designed chemosensitizers, some
      still suffer from toxicity and adverse effects, whereas others progressed to
      clinical trials. Diversities among tumors and among MDR pumps indicate a need for
      several clinically approved MDR modulators. Here we report for the first time
      that fluoxetine (Prozac), the well-known antidepressant, is a highly effective
      chemosensitizer. In vitro, fluoxetine enhanced (10- to 100-fold) cytotoxicity of
      anticancer drugs (doxorubicin, mitomycin C, vinblastine, and paclitaxel) in drug
      resistant but not in drug-sensitive cells (5 and 3 lines, respectively).
      Fluoxetine increased drug accumulation within MDR-cells and inhibited drug efflux
      from those cells. In vivo, fluoxetine enhanced doxorubicin accumulation within
      tumors (12-fold) with unaltered pharmacokinetics. In four resistant mouse tumor
      models of both syngeneic and human xenograft, combination treatment of fluoxetine
      and doxorubicin generated substantial (P < 0.001) improvements in tumor responses
      and in survivals (2- to 3-fold). Moreover, fluoxetine reversed MDR at doses that
      are well below its human safety limits, free of the severe dose-related toxicity,
      adverse effects, and poor solubility that are obstacles to other
      chemosensitizers. This low-dose range, together with the findings reported here,
      indicate that fluoxetine has a high potential to join the arsenal of MDR reversal
      agents that may reach the clinic.

PMID- 15492284
TI  - c-Jun NH2-terminal kinase-mediated up-regulation of death receptor 5 contributes
      to induction of apoptosis by the novel synthetic triterpenoid methyl-2-cyano-3,12
      dioxooleana-1, 9-dien-28-oate in human lung cancer cells.
AB  - Death receptor (DR) 4 or 5, on binding to its ligand, tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL), triggers apoptosis via activating the
      caspase-8-mediated caspase cascade. Certain anticancer drugs up-regulate the
      expression of these receptors and thereby induce apoptosis or enhance TRAIL
      induced apoptosis. In this study, we explored the ability of methyl-2-cyano-3,12
      dioxooleana-1,9-dien-28-oate (CDDO-Me) to activate the extrinsic DR-mediated
      apoptotic pathway in human lung cancer cells. We found that CDDO-Me not only
      activated caspase-8 but also induced expression of DRs, particularly DR5, in a
      p53-independent mechanism. Correspondingly, CDDO-Me augmented TRAIL-induced
      apoptosis in these cells regardless of p53 status as evidenced by enhanced DNA
      fragmentation and activation of caspase cascades, suggesting that CDDO-Me-induced
      DRs are functionally active. Moreover, silencing of DR5 expression using small
      interfering RNA suppressed apoptosis induced by CDDO-Me alone or by combination
      of CDDO-Me and TRAIL, indicating that DR5 up-regulation is required for induction
      of apoptosis by CDDO-Me and for enhancement of TRAIL-induced apoptosis by CDDO
      Me. CDDO-Me rapidly activated c-Jun NH(2)-terminal kinase (JNK) before DR up
      regulation and caspase-8 activation. Moreover, application of the JNK-specific
      inhibitor SP600125 blocked CDDO-Me-induced increases in JNK activation, DR up
      regulation, caspase-8 activation, and DNA fragmentation. These results show that
      activation of JNK pathway results in CDDO-Me-induced DR up-regulation, caspase-8
      activation, and apoptosis. Collectively, we conclude that CDDO-Me induces
      apoptosis via the JNK-mediated DR up-regulation in human lung cancer cells.

PMID- 15492285
TI  - CC chemokine ligand 25 enhances resistance to apoptosis in CD4+ T cells from
      patients with T-cell lineage acute and chronic lymphocytic leukemia by means of
      livin activation.
AB  - We investigated CD4 and CD8 double-positive thymocytes, CD4(+) T cells from
      typical patients with T-cell lineage acute lymphocytic leukemia (T-ALL) and T
      cell lineage chronic lymphocytic leukemia (T-CLL), and MOLT4 T cells in terms of
      CC chemokine ligand 25 (CCL25) functions of induction of resistance to tumor
      necrosis factor alpha (TNF-alpha)-mediated apoptosis. We found that CCL25
      selectively enhanced resistance to TNF-alpha-mediated apoptosis in T-ALL and T
      CLL CD4(+) T cells as well as in MOLT4 T cells, but CD4 and CD8 double-positive
      thymocytes did not. One member protein of the inhibitor of apoptosis protein
      (IAP) family, Livin, was selectively expressed in the malignant cells at higher
      levels, particularly in T-ALL CD4(+) T cells, in comparison with the expression
      in CD4 and CD8 double-positive thymocytes. After stimulation with CCL25 and
      apoptotic induction with TNF-alpha, the expression levels of Livin in these
      malignant cells were significantly increased. CCL25/thymus-expressed chemokine
      (TECK), by means of CC chemokine receptor 9 (CCR9) ligation, selectively
      activated Livin to enhance resistance to TNF-alpha-mediated apoptosis in c-jun
      NH(2)-kinase 1 (JNK1) kinase-dependent manner. These findings suggested
      differential functions of CCR9/CCL25 in distinct types of cells. CD4 and CD8
      double-positive thymocytes used CCR9/CCL25 for migration, homing, development,
      maturation, selection, cell homeostasis, whereas malignant cells, particularly T
      ALL CD4(+) T cells, used CCR9/CCL25 for infiltration, resistance to apoptosis,
      and inappropriate proliferation.

PMID- 15492286
TI  - Anti-HER-2/neu immune responses are induced before the development of clinical
      tumors but declined following tumorigenesis in HER-2/neu transgenic mice.
AB  - HER-2/neu oncogene products have been implicated as a potential target of T cell
      mediated immune responses to HER-2/neu-induced tumors. Using HER-2/neu transgenic
      mice (oncomice), we investigated whether, and if so how, anti-HER-2/neu immune
      responses are induced and modulated in these oncomice from birth to tumor
      initiation. Female oncomice carrying the activated HER-2/neu oncogene displayed
      apparent hyperplasia in mammary glands at 10 weeks of age and developed mammary
      carcinomas around an average age of 26 weeks. Unfractionated spleen cells from 10
      to 15-week-old oncomice that were cultured without any exogenous stimuli
      exhibited cytotoxicity against the F31 tumor cell line established from an HER
      2/neu-induced mammary carcinoma mass. The final antitumor effectors were a
      macrophage lineage of cells. However, this effector population was activated,
      depending on the stimulation of oncomouse CD4(+) T cells with oncomouse-derived
      antigen-presenting cell (APC) alone or with wild-type mouse APC in the presence
      of F31 membrane fractions, suggesting the presence of HER-2/neu-primed CD4(+) T
      cells and HER-2/neu-presenting APC in 10- to 15-week-old oncomice. These
      antitumor cytotoxic responses were detected at approximately 5 weeks of age and
      peaked at age 10 to 15 weeks. However, the responses then declined at tumor
      bearing stages in which the expression of target proteins could progressively
      increase. This resulted from the dysfunction of CD4(+) T cells but not of APC or
      effector macrophages. These results indicate that an anti-HER-2/neu CD4(+) T cell
      mediated immune response was generated at the pretumorigenic stage but did not
      prevent tumorigenesis and declined after the development of clinical tumors.

PMID- 15492287
TI  - RNA interference targeting transforming growth factor-beta enhances NKG2D
      mediated antiglioma immune response, inhibits glioma cell migration and
      invasiveness, and abrogates tumorigenicity in vivo.
AB  - Transforming growth factor (TGF)-beta is the key molecule implicated in impaired
      immune function in human patients with malignant gliomas. Here we report that
      patients with glioblastoma, the most common and lethal type of human glioma, show
      decreased expression of the activating immunoreceptor NKG2D in CD8(+) T and
      natural killer (NK) cells. TGF-beta is responsible for the down-regulation of
      NKG2D expression in CD8(+) T and NK cells mediated by serum and cerebrospinal
      fluid of glioma patients in vitro. Moreover, TGF-beta inhibits the transcription
      of the NKG2D ligand MICA. Interference with the synthesis of TGF-beta1 and TGF
      beta2 by small interfering RNA technology prevents the down-regulation of NKG2D
      on immune cells mediated by LNT-229 glioma cell supernatant and strongly enhances
      MICA expression in the glioma cells and promotes their recognition and lysis by
      CD8(+) T and NK cells. Furthermore, TGF-beta silencing results in a less
      migratory and invasive glioma cell phenotype in vitro. LNT-229 glioma cells
      deficient in TGF-beta exhibit a loss of subcutaneous and orthotopic
      tumorigenicity in nude mice, and NK cells isolated from these mice show an
      activated phenotype. RNA interference targeting TGF-beta1,2 results in a glioma
      cell phenotype that is more sensitive to immune cell lysis and less motile in
      vitro and nontumorigenic in nude mice, strongly confirming TGF-beta antagonism as
      a major therapeutic strategy for the future treatment of malignant gliomas.

PMID- 15492288
TI  - 17beta-hydroxysteroid dehydrogenase type 1 is an independent prognostic marker in
      breast cancer.
AB  - Estrogens have an important role in the development and progression of breast
      cancer. 17beta-Hydroxysteroid dehydrogenase type 1 (17HSD1), type 2 (17HSD2), and
      type 5 (17HSD5) are associated with sex steroid metabolism in normal and
      cancerous breast tissue. The mRNA expressions of the 17HSD1, 17HSD2, and 17HSD5
      enzymes were analyzed in 794 breast carcinoma specimens by using tissue
      microarrays and normal histologic sections. The results were correlated with the
      estrogen receptor alpha (ER-alpha) and beta (ER-beta), progesterone receptor,
      Ki67, and c-erbB-2 expressions analyzed by immunohistochemical techniques and
      with the Tumor-Node-Metastasis classification, tumor grade, disease-free
      interval, and survival of the patients. Signals for 17HSD1 mRNA were detected in
      16%, 17HSD2 in 25%, and 17HSD5 in 65% of the breast cancer specimens. No
      association between the 17HSD1, 17HSD2, and 17HSD5 expressions was detected. A
      significant association was observed between ER-alpha and ER-beta (P = 0.02; odds
      ratio, 1.96) expressions. There was also a significant inverse association
      between ER-alpha and 17HSD1 (P = 0.04; odds ratio, 0.53), as well as ER-alpha and
      17HSD5 (P = 0.001; odds ratio, 0.35). Patients with tumors expressing 17HSD1 mRNA
      or protein had significantly shorter overall and disease-free survival than the
      other patients (P = 0.0010 and 0.0134, log rank). The expression of 17HSD5 was
      significantly higher in breast tumor specimens than in normal tissue (P = 0.033;
      odds ratio, 5.56). The group with 17HSD5 overexpression had a worse prognosis
      than the other patients (P = 0.0146). ER-alpha also associated with survival (P =
      0.045). Cox multivariate analyses showed that 17HSD1 mRNA, tumor size, and ER
      alpha had independent prognostic significance.

PMID- 15492289
TI  - Selective loss of AKR1C1 and AKR1C2 in breast cancer and their potential effect
      on progesterone signaling.
AB  - Progesterone plays an essential role in breast development and cancer formation.
      The local metabolism of progesterone may limit its interactions with the
      progesterone receptor (PR) and thereby act as a prereceptor regulator. Selective
      loss of AKR1C1, which encodes a 20alpha-hydroxysteroid dehydrogenase [20alpha-HSD
      (EC 1.1.1.149)], and AKR1C2, which encodes a 3alpha-hydroxysteroid dehydrogenase
      [3alpha-HSD (EC 1.1.1.52)], was found in 24 paired breast cancer samples as
      compared with paired normal tissues from the same individuals. In contrast,
      AKR1C3, which shares 84% sequence identity, and 5alpha-reductase type I (SRD5A1)
      were minimally affected. Breast cancer cell lines T-47D and MCF-7 also expressed
      reduced AKR1C1, whereas the breast epithelial cell line MCF-10A expressed AKR1C1
      at levels comparable with those of normal breast tissues. Immunohistochemical
      staining confirmed loss of AKR1C1 expression in breast tumors. AKR1C3 and AKR1C1
      were localized on the same myoepithelial and luminal epithelial cell layers.
      Suppression of ARK1C1 and AKR1C2 by selective small interfering RNAs inhibited
      production of 20alpha-dihydroprogesterone and was associated with increased
      progesterone in MCF-10A cells. Suppression of AKR1C1 alone or with AKR1C2 in T
      47D cells led to decreased growth in the presence of progesterone. Overexpression
      of AKR1C1 and, to a lesser extent, AKR1C2 (but not AKR1C3) decreased progesterone
      dependent PR activation of a mouse mammary tumor virus promoter in both prostate
      (PC-3) and breast (T-47D) cancer cell lines. We speculate that loss of AKR1C1 and
      AKR1C2 in breast cancer results in decreased progesterone catabolism, which, in
      combination with increased PR expression, may augment progesterone signaling by
      its nuclear receptors.

PMID- 15492290
TI  - The CpG island methylator phenotype is not associated with a personal or family
      history of cancer.
AB  - Colorectal cancers with widespread CpG island methylation display a number of
      distinct clinicopathological features, and it has been suggested that the
      condition has an inheritable genetic component. To address this possibility,
      histories of cancer were obtained from 562 individuals undergoing curative
      surgery for unselected colorectal cancer at one institution. Microsatellite
      status and methylation at p16, MINT1, 2, 12, and 31 loci were determined on fresh
      tumor tissue using standard methods. Fifty-five of 562 probands in this study
      provided a personal history of at least one other colorectal cancer, 10 reported
      at least one extracolonic cancer of hereditary nonpolyposis colorectal cancer
      type, and 84 individuals had another type of cancer. Age was strongly associated
      with the risk of multiple cancers, but there was no evidence that microsatellite
      instability or the CpG island methylator phenotype were independent risk factors
      for their development, either in the colorectum or elsewhere. Of the 547
      individuals with knowledge of their family history, 80 (14.6%) reported a family
      history of colorectal cancer in a first-degree relative, and 60% of individuals
      reported a history of any cancer in a first-degree relative. Neither tumor CpG
      island methylator phenotype status nor microsatellite instability was predictive
      of a positive history of cancer in first- or second-degree relatives. The
      probability of a positive family or personal history of cancer did not increase
      with increasing number of methylated loci. Epigenetic silencing of multiple genes
      seen in some tumors is at best rarely the result of an inherited defect in the
      methylation apparatus. There is no justification for altering the personal or
      family cancer screening recommendations on the basis of tumor CpG island
      methylator phenotype status.

PMID- 15492291
TI  - Functional haplotypes in the promoter of matrix metalloproteinase-2 predict risk
      of the occurrence and metastasis of esophageal cancer.
AB  - Matrix metalloproteinase-2 (MMP-2) plays important roles in cancer development
      and aggression. Our previous studies revealed a strong association between the
      MMP-2 -1306C/T polymorphism and risk of several cancers. A novel -735C/T
      polymorphism in MMP-2 promoter has been identified but the function is undefined.
      This study examined our hypothesis that these two polymorphisms might have
      functional relevance and impact on risk of esophageal squamous cell carcinoma in
      the context of haplotype. Genotypes and haplotypes were analyzed in 527 cases and
      777 controls and odds ratios (ORs) and 95% confidence intervals (CIs) were
      estimated by logistic regression. The function of the polymorphisms was examined
      by electrophoretic mobility shift assays, luciferase gene expression assays, and
      reverse transcriptase-PCR analyses. It was found that the -735C-->T transition
      disrupts an Sp1 site and displays a lower promoter activity. The C(-1306)-C(-735)
      haplotype had 7-fold increased luciferase expression and 3.7-fold increased MMP-2
      mRNA levels in esophageal tissues compared with the T(-1306)-T(-735) haplotype. A
      case-control analysis revealed a 1.52-fold (95% CI = 1.17-1.96) or 1.30-fold (95%
      CI = 1.04-1.63) excess risk of developing esophageal squamous cell carcinoma for
      the -1306CC or -735CC genotype carriers compared with noncarriers, respectively.
      A greater association was observed between elevated risk of developing esophageal
      squamous cell carcinoma and C(-1306) or C(-735) allele containing haplotypes,
      with the risk being highest for the C(-1306)-C(-735) haplotype compared with the
      T(-1306)-T(-735) haplotype (OR = 6.53; 95% CI = 2.78-15.33). The C(-1306)-C(-735)
      haplotype was also associated with increased risk for distant metastasis of
      esophageal squamous cell carcinoma (OR = 3.34; 95% CI = 1.16-9.63). These
      findings suggest that the C(-1306)-C(-735) haplotype in the MMP-2 promoter
      contributes to risk of the occurrence and metastasis of esophageal squamous cell
      carcinoma by increasing expression of MMP-2.

PMID- 15492292
TI  - The combination of genetic instability and clonal expansion predicts progression
      to esophageal adenocarcinoma.
AB  - There is debate in the literature over the relative importance of genetic
      instability and clonal expansion during progression to cancer. Barrett's
      esophagus is a uniquely suited model to investigate neoplastic progression
      prospectively because periodic endoscopic biopsy surveillance is recommended for
      early detection of esophageal adenocarcinoma. We hypothesized that expansion of
      clones with genetic instability would predict progression to esophageal
      adenocarcinoma. We measured p16 (CDKN2A/INK4A) lesions (loss of heterozygosity,
      mutations, and CpG island methylation), p53 (TP53) lesions (loss of
      heterozygosity, mutation) and ploidy abnormalities (aneuploidy, tetraploidy)
      within each Barrett's esophagus segment of a cohort of 267 research participants,
      who were followed prospectively with cancer as an outcome. We defined the size of
      a lesion as the fraction of cells with the lesion multiplied by the length of the
      Barrett's esophagus segment. A Cox proportional hazards regression indicates that
      the sizes of clones with p53 loss of heterozygosity (relative risk = 1.27(x) for
      an x cm clone; 95% confidence interval, 1.07-1.50) or ploidy abnormalities
      (relative risk = 1.31(x) for an x cm clone; 95% confidence interval, 1.07-1.60)
      predict progression to esophageal adenocarcinoma better than the mere presence of
      such clones (likelihood ratio test, P < 0.01). Controlling for length of the
      Barrett's esophagus segment had little effect. The size of a clone with a p16
      lesion is not a significant predictor of esophageal adenocarcinoma when we
      controlled for p53 loss of heterozygosity status. The combination of clonal
      expansion and genetic instability is a better predictor of cancer outcome than
      either alone. This implies that interventions that limit expansion of genetically
      unstable clones may reduce risk of progression to cancer.

PMID- 15492293
TI  - Myeloperoxidase genotype, fruit and vegetable consumption, and breast cancer
      risk.
AB  - Myeloperoxidase (MPO), an antimicrobial enzyme in the breast, generates reactive
      oxygen species (ROS) endogenously. An MPO G463A polymorphism exists in the
      promoter region, with the variant A allele conferring lower transcription
      activity than the common G allele. Because oxidative stress may play a role in
      breast carcinogenesis, we evaluated MPO genotypes in relation to breast cancer
      risk among 1,011 cases and 1,067 controls from the Long Island Breast Cancer
      Study Project (1996-1997). We also assessed the potential modifying effects of
      dietary antioxidants and hormonally related risk factors on these relationships.
      Women over 20 years with incident breast cancer who were residents of Nassau and
      Suffolk Counties, NY, were identified as potential cases. Population-based
      controls were frequency matched by 5-year age groups. Genotyping was performed
      with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF) technology, and suspected breast cancer risk factors and usual
      dietary intake were assessed during an in-person interview. Unconditional
      logistic regression was used to estimate odds ratios and 95% confidence
      intervals. Having at least one A allele was associated with an overall 13%
      reduction in breast cancer risk. When consumption of fruits and vegetables and
      specific dietary antioxidants were dichotomized at the median, inverse
      associations with either GA or AA genotypes were most pronounced among women who
      consumed higher amounts of total fruits and vegetables (odds ratio, 0.75; 95%
      confidence interval, 0.58-0.97); this association was not noted among the low
      consumption group (P for interaction = 0.04). Relationships were strongest among
      premenopausal women. Results from this first study of MPO genotypes and breast
      cancer risk indicate that MPO variants, related to reduced generation of ROS, are
      associated with decreased breast cancer risk, and emphasize the importance of
      fruit and vegetable consumption in reduction of breast cancer risk.

PMID- 15492294
TI  - Highlights of the National Cancer Institute Workshop on mitochondrial function
      and cancer.

PMID- 15492296
TI  - Weathering the influenza vaccine crisis.

PMID- 15492297
TI  - Predictive value of 16-slice multidetector spiral computed tomography to detect
      significant obstructive coronary artery disease in patients at high risk for
      coronary artery disease: patient-versus segment-based analysis.
AB  - BACKGROUND: In this study, we investigated the diagnostic value and limitations
      of multidetector computed tomography (MDCT)-based noninvasive detection of
      significant obstructive coronary artery disease (CAD) in a consecutive high-risk
      patient population with inclusion of all coronary segments. METHODS AND RESULTS:
      In a prospective, blinded, standard cross-sectional technology assessment, a
      cohort of 33 consecutive patients with a positive stress test result underwent 16
      slice MDCT and selective coronary angiography for the detection of significant
      obstructive CAD. We assessed the diagnostic accuracy of MDCT in a segment-based
      and a patient-based model and determined the impact of stenosis location and the
      presence of calcification on diagnostic accuracy in both models. Analysis of all
      530 coronary segments demonstrated moderate sensitivity (63%) and excellent
      specificity (96%) with a moderate positive predictive value of 64% and an
      excellent negative predictive value (NPV) of 96% for the detection of significant
      coronary stenoses. Assessment restricted to either proximal coronary segments or
      segments with excellent image quality (83% of all segments) led to an increase in
      sensitivity (70% and 82%, respectively), and high specificities were maintained
      (94% and 93%, respectively). In a patient-based model, the NPV of MDCT for
      significant CAD was limited to 75%. Coronary calcification was the major cause of
      false-positive findings (94%). CONCLUSIONS: For all coronary segments included,
      16-slice MDCT has moderate diagnostic value for the detection of significant
      obstructive coronary artery stenosis in a population with a high prevalence of
      CAD. The moderate NPV of patient-based detection of CAD suggests a limited impact
      on clinical decision-making in high-risk populations.

PMID- 15492298
TI  - Mortality and morbidity reduction with Candesartan in patients with chronic heart
      failure and left ventricular systolic dysfunction: results of the CHARM low-left
      ventricular ejection fraction trials.
AB  - BACKGROUND: Patients with symptomatic chronic heart failure (CHF) and reduced
      left ventricular ejection fraction (LVEF) have a high risk of death and
      hospitalization for CHF deterioration despite therapies with angiotensin
      converting enzyme (ACE) inhibitors, beta-blockers, and even an aldosterone
      antagonist. To determine whether the angiotensin-receptor blocker (ARB)
      candesartan decreases cardiovascular mortality, morbidity, and all-cause
      mortality in patients with CHF and depressed LVEF, a prespecified analysis of the
      combined Candesartan in Heart Failure Assessment of Reduction in Mortality and
      morbidity (CHARM) low LVEF trials was performed. CHARM is a randomized, double
      blind, placebo-controlled, multicenter, international trial program. METHODS AND
      RESULTS: New York Heart Association (NYHA) class II through IV CHF patients with
      an LVEF of < or =40% were randomized to candesartan or placebo in 2 complementary
      parallel trials (CHARM-Alternative, for patients who cannot tolerate ACE
      inhibitors, and CHARM-Added, for patients who were receiving ACE inhibitors).
      Mortality and morbidity were determined in 4576 low LVEF patients (2289
      candesartan and 2287 placebo), titrated as tolerated to a target dose of 32 mg
      once daily, and observed for 2 to 4 years (median, 40 months). The primary
      outcome (time to first event by intention to treat) was cardiovascular death or
      CHF hospitalization for each trial, with all-cause mortality a secondary end
      point in the pooled analysis of the low LVEF trials. Of the patients in the
      candesartan group, 817 (35.7%) experienced cardiovascular death or a CHF
      hospitalization as compared with 944 (41.3%) in the placebo group (HR 0.82; 95%
      CI 0.74 to 0.90; P<0.001) with reduced risk for both cardiovascular deaths (521
      [22.8%] versus 599 [26.2%]; HR 0.84 [95% CI 0.75 to 0.95]; P=0.005) and CHF
      hospitalizations (516 [22.5%] versus 642 [28.1%]; HR 0.76 [95% CI 0.68 to 0.85];
      P<0.001). It is important to note that all-cause mortality also was significantly
      reduced by candesartan (642 [28.0%] versus 708 [31.0%]; HR 0.88 [95% CI 0.79 to
      0.98]; P=0.018). No significant heterogeneity for the beneficial effects of
      candesartan was found across prespecified and subsequently identified subgroups
      including treatment with ACE inhibitors, beta-blockers, an aldosterone
      antagonist, or their combinations. The study drug was discontinued because of
      adverse effects by 23.1% of patients in the candesartan group and 18.8% in the
      placebo group; the reasons included increased creatinine (7.1% versus 3.5%),
      hypotension (4.2% versus 2.1%), and hyperkalemia (2.8% versus 0.5%), respectively
      (all P<0.001). CONCLUSIONS: Candesartan significantly reduces all-cause
      mortality, cardiovascular death, and heart failure hospitalizations in patients
      with CHF and LVEF < or =40% when added to standard therapies including ACE
      inhibitors, beta-blockers, and an aldosterone antagonist. Routine monitoring of
      blood pressure, serum creatinine, and serum potassium is warranted.

PMID- 15492299
TI  - Extraction of pulmonary vascular compliance, pulmonary vascular resistance, and
      right ventricular work from single-pressure and Doppler flow measurements in
      children with pulmonary hypertension: a new method for evaluating reactivity: in
      vitro and clinical studies.
AB  - BACKGROUND: Current evaluation of pulmonary hypertension (PH) in children
      involves measurement of pulmonary vascular resistance (PVR); however, PVR
      neglects important pulsatile components. Pulmonary artery (PA) input impedance
      and ventricular power (VP) include mean and pulsatile effects and have shown
      promise as alternative measures of vascular function. Here we report the utility
      of pulsed-wave (PW) Doppler-measured instantaneous flow and pressure measurements
      for estimation of input impedance and VP and use this method to develop a novel
      parameter: reactivity in compliance. METHODS AND RESULTS: An in vitro model of
      the general pulmonary vasculature was used to obtain impedance and VP, measured
      by PW Doppler and a reference flow meter. The method was then tested in a
      preliminary clinical study in subjects with normal PA hemodynamics (n=4) and
      patients with PH undergoing reactivity evaluation (8 patients; 23 data points).
      In vitro results showed good agreement between the impedance spectra computed
      from both flow-measurement methods. Excellent correlation was seen in vitro
      between actual resistance and the zero-frequency (Z(o)) impedance value
      (r2=0.984). Excellent agreement was also found between Z(o) and PVR in the
      clinical measurements (y=1.075x+0.73; r=0.993). Furthermore, total VP and
      VP/cardiac output increased significantly with hypertension (128.73 to 365.91 mW
      and 2.42 to 6.69 mW x mL(-1) x s(-1), respectively). The first-harmonic value of
      impedance (Z1) was used as a measure of compliance reactivity; older patients
      exhibited markedly less compliance reactivity than did younger patients.
      CONCLUSIONS: Input impedance and VP calculated from Doppler measurements and a
      single-catheter pressure measurement provide comprehensive characterization of PH
      and reactivity.

PMID- 15492300
TI  - Ascorbic acid prevents contrast-mediated nephropathy in patients with renal
      dysfunction undergoing coronary angiography or intervention.
AB  - BACKGROUND: Contrast agents can cause a reduction in renal function that may be
      due to the generation of reactive oxygen species. Conflicting evidence suggests
      that administration of the antioxidant acetylcysteine prevents this renal
      impairment. The action of other antioxidant agents has not been investigated.
      METHODS AND RESULTS: We conducted a randomized, double-blind, placebo-controlled
      trial of ascorbic acid in 231 patients with a serum creatinine concentration > or
      =1.2 mg/dL who underwent coronary angiography and/or intervention. Ascorbic acid,
      3 g at least 2 hours before the procedure and 2 g in the night and the morning
      after the procedure, or placebo was administered orally. Contrast-mediated
      nephropathy was defined by an absolute increase of serum creatinine > or =0.5
      mg/dL or a relative increase of > or =25% measured 2 to 5 days after the
      procedure. Contrast-mediated nephropathy occurred in 11 of the 118 patients (9%)
      in the ascorbic acid group and in 23 of the 113 patients (20%) in the placebo
      group (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.17 to 0.85;
      P=0.02). The mean serum creatinine concentration increased significantly in the
      placebo group (from 1.36+/-0.50 to 1.50+/-0.54 mg/dL, P<0.001) and
      nonsignificantly in the ascorbic acid group (from 1.46+/-0.52 to 1.52+/-0.64
      mg/dL, P=0.07). The mean increase in serum creatinine concentration was greater
      in the placebo group than in the ascorbic acid group (difference of 0.09 mg/dL;
      95% CI, 0.00 to 0.17; P=0.049). CONCLUSIONS: Prophylactic oral administration of
      ascorbic acid may protect against contrast-mediated nephropathy in high-risk
      patients undergoing a coronary procedure.

PMID- 15492301
TI  - Unfavorable effects of resistance training on central arterial compliance: a
      randomized intervention study.
AB  - BACKGROUND: Reductions in the compliance of central arteries exert a number of
      adverse effects on cardiovascular function and disease risk. Endurance training
      is efficacious in increasing arterial compliance in healthy adults. We determined
      the effects of resistance training on carotid arterial compliance using the
      intervention study design. METHODS AND RESULTS: Twenty-eight healthy men 20 to 38
      years old were randomly assigned to the intervention group (n=14) and the control
      group (n=14). Control subjects were instructed not to alter their normal activity
      levels throughout the study period. Intervention subjects underwent 3 supervised
      resistance training sessions per week for 4 months and detraining for a
      subsequent 4 months. The resistance training increased maximal strength in all
      muscle groups tested (P<0.001). There were no significant differences in baseline
      arterial compliance and beta-stiffness index between the intervention and control
      groups. In the intervention group, carotid arterial compliance decreased 19%
      (P<0.05), and beta-stiffness index increased 21% (P<0.01) after resistance
      training. These values returned completely to the baseline levels during the
      detraining period. Arterial compliance did not change in the control group. In
      both groups, there were no significant changes in brachial and carotid blood
      pressure, carotid intima-media thickness, lumen diameter, and femoral arterial
      compliance. Changes in carotid artery compliance were significantly and
      negatively related to corresponding changes in left ventricular mass index (r=
      0.56, P<0.001) and left ventricular hypertrophy index (r=-0.68, P<0.001).
      CONCLUSIONS: In marked contrast to the beneficial effect of regular aerobic
      exercise, several months of resistance training "reduces" central arterial
      compliance in healthy men.

PMID- 15492302
TI  - Correlations between fractional flow reserve and intravascular ultrasound in
      patients with an ambiguous left main coronary artery stenosis.
AB  - BACKGROUND: Intravascular ultrasound (IVUS) is being used to assess the
      significance of a left main coronary artery stenosis (LMCS). However, the cutoff
      values of IVUS parameters at which to predict a fractional flow reserve (FFR) of
      0.75 are unknown. METHODS AND RESULTS: In 55 patients with an angiographically
      ambiguous LMCS, a pressure guidewire was used to calculate FFR, and IVUS
      parameters were calculated after automatic pullback. FFR averaged 0.86+/-0.13
      (range, 0.55 to 1.0). IVUS minimum lumen diameter (MLD), minimum lumen area
      (MLA), cross-sectional narrowing (CSN), and area stenosis (AS) were 3.8+/-0.61
      mm, 7.65+/-2.9 mm2, 59+/-13%, and 47+/-19%, respectively. Regression analysis
      demonstrated strong correlations between FFR and MLD (r=0.79, P<0.0001) as well
      as between FFR and MLA (r=0.74, P<0.0001). There were inverse, moderate
      correlations between FFR and CSN (r=0.69, P<0.0001), followed by those between
      FFR and AS (r=0.54, P<0.0001). Compared with FFR as the "gold standard," an MLD
      of 2.8 mm had the highest sensitivity and specificity (93% and 98%, respectively)
      for determining the significance of an LMCS, followed by an MLA of 5.9 mm2 (93%
      and 95%, respectively). Based on an FFR <0.75 and an FFR > or =0.75, the 38-month
      survival and event-free survival estimates (EFSEs) were both 100% and 100% versus
      90%, respectively (P=NS). CONCLUSIONS: We conclude that (1) an IVUS MLD and MLA
      of 2.8 mm and 5.9 mm2, respectively, strongly predict the physiological
      significance of an LMCS and (2) among patients with an LMCS, an FFR of 0.75 is a
      strong predictor of survival and EFSE.

PMID- 15492303
TI  - Evolution of spontaneous atherosclerotic plaque rupture with medical therapy:
      long-term follow-up with intravascular ultrasound.
AB  - BACKGROUND: Ruptured coronary atheromatous plaque is generally considered to
      involve a high risk of subsequent clinical events. Few data are available on the
      natural evolution of non-culprit-lesion ruptured plaque. We therefore used serial
      intravascular ultrasound (IVUS) to study how such lesions, detected in the
      context of a first acute coronary syndrome with elevated troponin I levels,
      develop. METHODS AND RESULTS: Fourteen patients with 28 distinct plaque ruptures
      (2+/-1 per patient) without significant associated stenosis (minimal lumen cross
      sectional area >4 mm2) were included and systematically treated with 40 mg statin
      and antiplatelet agent (clopidogrel and aspirin for > or =9 months). Mean
      clinical and IVUS follow-up was 22+/-13 months (median, 22 months). No clinical
      event related to the lesion under study occurred. On final IVUS examination, half
      (14 of 28) of the ruptured plaques had healed, and the degree of stenosis tended
      to diminish (stenosis, 22+/-17% versus 29+/-17% at baseline; P=0.056). No healing
      prediction criterion could be identified. CONCLUSIONS: Nearly 2 years of follow
      up found that spontaneous coronary atheromatous plaque rupture without
      significant stenosis detected on first acute coronary syndrome healed without
      significant plaque modification in 50% of cases with medical therapy.

PMID- 15492304
TI  - Comparison of the associations of apolipoprotein B and non-high-density
      lipoprotein cholesterol with other cardiovascular risk factors in patients with
      the metabolic syndrome in the Insulin Resistance Atherosclerosis Study.
AB  - BACKGROUND: The metabolic syndrome (MetS) as defined by the National Cholesterol
      Education Panel definition has been proposed as an indicator of cardiovascular
      disease risk. Both apolipoprotein (apo)B and non-HDL cholesterol (NHDLC) have
      been proposed as an additional indicator to identify patients at higher risk in
      MetS patients. METHODS AND RESULTS: We studied 1522 individuals in the Insulin
      Resistance Atherosclerosis Study (IRAS) who were 40 to 69 years of age and from 3
      ethnic groups. Their anthropometric measures, lipids, apoB, C-reactive protein,
      fibrinogen, plasminogen activator inhibitor-1, fasting and post-glucose load
      glucose, and insulin concentrations were measured, and insulin sensitivity was
      determined by intravenous glucose tolerance test. Differences in risk parameters
      in individuals with hyper-apoB/normo-NHDLC, and normo-apoB/hyper-NHDLC were
      compared in all IRAS subjects and again in those with MetS. In both cases,
      despite anticipated lower LDL cholesterol, the hyper-apoB/normo-NHDLC group had
      elevated risk indicated by greater waist circumference (both P<0.05) and fasting
      insulin (P<0.01) and lower insulin sensitivity (P<0.001). They also had higher C
      reactive protein (P<0.05). Moreover, the Spearman correlation of apoB was
      significantly stronger (P<0.05) in the direction of greater associated risk than
      that of NHDLC with body mass index, waist circumference, systolic blood pressure,
      2-hour glucose, fasting glucose, fasting insulin, 2-hour insulin, insulin
      sensitivity, C-reactive protein, fibrinogen, and plasminogen activator inhibitor
      1. CONCLUSIONS: In conclusion, apoB is more closely associated with central
      adiposity, insulin resistance, thrombosis, and inflammation than NHDLC. Our data
      suggest that apoB is a better candidate risk parameter than NHDLC for identifying
      a subgroup of individuals with or without MetS with elevated cardiovascular risk.

PMID- 15492305
TI  - Serum triglycerides as a risk factor for cardiovascular diseases in the Asia
      Pacific region.
AB  - BACKGROUND: The importance of serum triglyceride levels as a risk factor for
      cardiovascular diseases is uncertain. METHODS AND RESULTS: We performed an
      individual participant data meta-analysis of prospective studies conducted in the
      Asia-Pacific region. Cox models were applied to the combined data from 26 studies
      to estimate the overall and region-, sex-, and age-specific hazard ratios for
      major cardiovascular diseases by fifths of triglyceride values. During 796,671
      person-years of follow-up among 96,224 individuals, 670 and 667 deaths as a
      result of coronary heart disease (CHD) and stroke, respectively, were recorded.
      After adjustment for major cardiovascular risk factors, participants grouped in
      the highest fifth of triglyceride levels had a 70% (95% CI, 47 to 96) greater
      risk of CHD death, an 80% (95% CI, 49 to 119) higher risk of fatal or nonfatal
      CHD, and a 50% (95% CI, 29% to 76%) increased risk of fatal or nonfatal stroke
      compared with those belonging to the lowest fifth. The association between
      triglycerides and CHD death was similar across subgroups defined by ethnicity,
      age, and sex. CONCLUSIONS: Serum triglycerides are an important and independent
      predictor of CHD and stroke risk in the Asia-Pacific region. These results may
      have clinical implications for cardiovascular risk prediction and the use of
      lipid-lowering therapy.

PMID- 15492306
TI  - Prospective randomized multicenter trial of empirical antitachycardia pacing
      versus shocks for spontaneous rapid ventricular tachycardia in patients with
      implantable cardioverter-defibrillators: Pacing Fast Ventricular Tachycardia
      Reduces Shock Therapies (PainFREE Rx II) trial results.
AB  - BACKGROUND: Successful antitachycardia pacing (ATP) terminates ventricular
      tachycardia (VT) up to 250 bpm without the need for painful shocks in implantable
      cardioverter-defibrillator (ICD) patients. Fast VT (FVT) >200 bpm is often
      treated by shock because of safety concerns, however. This prospective,
      randomized, multicenter trial compares the safety and utility of empirical ATP
      with shocks for FVT in a broad ICD population. METHODS AND RESULTS: We randomized
      634 ICD patients to 2 arms-standardized empirical ATP (n=313) or shock (n=321)
      for initial therapy of spontaneous FVT. ICDs were programmed to detect FVT when
      18 of 24 intervals were 188 to 250 bpm and 0 of the last 8 intervals were >250
      bpm. Initial FVT therapy was ATP (8 pulses, 88% of FVT cycle length) or shock at
      10 J above the defibrillation threshold. Syncope and arrhythmic symptoms were
      collected through patient diaries and interviews. In 11+/-3 months of follow-up,
      431 episodes of FVT occurred in 98 patients, representing 32% of ventricular
      tachyarrhythmias and 76% of those that would be detected as ventricular
      fibrillation and shocked with traditional ICD programming. ATP was effective in
      229 of 284 episodes in the ATP arm (81%, 72% adjusted). Acceleration, episode
      duration, syncope, and sudden death were similar between arms. Quality of life,
      measured with the SF-36, improved in patients with FVT in both arms but more so
      in the ATP arm. CONCLUSIONS: Compared with shocks, empirical ATP for FVT is
      highly effective, is equally safe, and improves quality of life. ATP may be the
      preferred FVT therapy in most ICD patients.

PMID- 15492307
TI  - Differentiation of bone marrow stromal cells into the cardiac phenotype requires
      intercellular communication with myocytes.
AB  - BACKGROUND: Bone marrow stromal cells (BMSCs) have the potential to differentiate
      into various cells and can transdifferentiate into myocytes if an appropriate
      cellular environment is provided. However, the molecular signals that underlie
      this process are not fully understood. In this study, we show that BMSC
      differentiation is dependent on communication with cells in their
      microenvironment. METHODS AND RESULTS: BMSCs were isolated from green fluorescent
      protein (GFP)-transgenic mice and cocultured with myocytes in a ratio of 1:40.
      Myocytes were obtained from neonatal rat ventricles. The differentiation of BMSCs
      in coculture was confirmed by immunohistochemistry, electron microscopy, and
      reverse transcription-polymerase chain reaction. Before coculturing, the BMSCs
      were negative for alpha-actinin and exhibited a nucleus with many nucleoli. After
      7-day coculture with myocytes, some BMSCs became alpha-actinin-positive and
      formed gap junctions with native myocytes. However, BMSCs separated from myocytes
      by a semipermeable membrane were still negative for alpha-actinin.
      Transdifferentiated myocytes from BMSCs were microdissected from cocultures by
      laser captured microdissection to determine the changes in gene expression. BMSCs
      cocultured with myocytes expressed mouse cardiac transcription factor GATA-4.
      CONCLUSIONS: When cocultured with myocytes, BMSCs can transdifferentiate into
      cells with a cardiac phenotype. Differentiated myocytes express cardiac
      transcription factors GATA-4 and myocyte enhancer factor-2. The
      transdifferentiation processes rely on intercellular communication of BMSCs with
      myocytes.

PMID- 15492308
TI  - Abnormalities of neurohormonal and cardiac autonomic nervous activities relate
      poorly to functional status in fontan patients.
AB  - BACKGROUND: Impaired cardiac autonomic nervous activities and increased
      neurohumoral activities (CANA, NHA) characterize Fontan patients. However, the
      clinical significance of these changes is not clearly understood. Our purpose was
      to clarify the clinical significance of the CANA and NHA in stable Fontan
      patients. METHODS AND RESULTS: We divided 22 atriopulmonary connection (APC) and
      75 total cavopulmonary connection (TCPC) patients into 4 subgroups according to
      New York Heart Association (NYHA) class (1.8+/-0.6) and measured various CANA and
      NHA indices. All NHA indices were elevated in the symptomatic patients (P<0.001).
      Natriuretic peptides were higher in the APC than in the TCPC patients, and the
      hemodynamics showed no correlation with brain natriuretic peptide in the APC
      patients. Low arterial oxygen saturation and impaired hemodynamics greatly
      influenced all elevated NHA indices (P<0.01), except for plasma renin activity,
      in the TCPC patients. Impaired CANA indices did not relate to NYHA class,
      although surgeries were associated with lower heart rate variability. In addition
      to poor correlation between NHA and CANA, age and ventricular morphology had no
      impact on all CANA and NHA indices, except for high norepinephrine in right
      ventricular Fontan patients. CONCLUSIONS: Although symptomatic Fontan patients
      exhibit higher NHA, CANA is not related to either NYHA class or NHA. APC itself
      is responsible for higher natriuretic peptides, and arterial oxygen desaturation
      has a great impact on elevated NHA in the TCPC patients. These characteristics of
      the NHA and CANA differ from those of heart failure patients with biventricular
      physiology.

PMID- 15492309
TI  - Tachycardia-related channel in the scar tissue in patients with sustained
      monomorphic ventricular tachycardias: influence of the voltage scar definition.
AB  - BACKGROUND: Endocardial mapping before sustained monomorphic ventricular
      tachycardia (SMVT) induction may reduce mapping time during tachycardia and
      facilitate the ablation of unmappable VT. METHODS AND RESULTS: Left ventricular
      electroanatomic voltage maps obtained during right ventricular apex pacing in 26
      patients with chronic myocardial infarction referred for VT ablation were
      analyzed to identify conducting channels (CCs) inside the scar tissue. A CC was
      defined by the presence of a corridor of consecutive electrograms differentiated
      by higher voltage amplitude than the surrounding area. The effect of different
      levels of voltage scar definition, from 0.5 to 0.1 mV, was analyzed. Twenty-three
      channels were identified in 20 patients. The majority of CCs were identified when
      the voltage scar definition was < or =0.2 mV. Electrograms with > or =2
      components were recorded more frequently at the inner than at the entrance of CCs
      (100% versus 75%, P< or =0.01). The activation time of the latest component was
      longer at the inner than at the entrance of CCs (200+/-40 versus 164+/-53 ms, P<
      or =0.001). Pacing from these CCs gave rise to a long-stimulus QRS interval
      (110+/-49 ms). Radiofrequency lesion applied to CCs suppressed the inducibility
      in 88% of CC-related tachycardias. During a follow-up of 17+/-11 months, 23% of
      the patients experienced a VT recurrence. CONCLUSIONS: CCs represent areas of
      slow conduction that can be identified in 75% of patients with SMVT. A tiered
      decreasing-voltage definition of the scar is critical for CC identification.

PMID- 15492310
TI  - Relation of postural vasovagal syncope to splanchnic hypervolemia in adolescents.
AB  - BACKGROUND: The mechanisms of simple faint remain elusive. We propose that
      postural fainting is related to excessive thoracic hypovolemia and splanchnic
      hypervolemia during orthostasis compared with healthy subjects. METHODS AND
      RESULTS: We studied 34 patients 12 to 22 years old referred for multiple episodes
      of postural faint and 11 healthy subjects. Subjects were studied in the supine
      position and during upright tilt to 70 degrees for 30 minutes and subgrouped into
      S+, historical fainters who fainted during testing (n=24); S-, historical
      fainters who did not faint during testing (n=10); and control subjects. Supine
      venous occlusion plethysmography showed no differences between blood flows of the
      forearm and calf in S+, S-, or control. Cardiac index, total peripheral
      resistance, and blood volume were not different. Using impedance plethysmography,
      we assessed blood redistribution during upright tilt. This demonstrated decreased
      thoracic blood volume and increased splanchnic, pelvic, and leg blood volumes for
      all subjects. However, thoracic blood volume was decreased in S+ compared with
      control volume, correlating well with the maximum upright heart rate. Splanchnic
      volume was decreased in the S+ and S- groups, correlating with the change in
      thoracic blood volume. Pelvic and leg volume changes were similar for all groups
      and uncorrelated to thoracic blood volume. CONCLUSIONS: Enhanced postural
      thoracic hypovolemia and splanchnic hypervolemia are associated with postural
      simple faint.

PMID- 15492311
TI  - Right bundle-branch block ventricular tachycardias: septal versus lateral
      ventricular origin based on activation time to the right ventricular apex.
AB  - BACKGROUND: Identifying the septal versus lateral site of origin of ventricular
      tachycardia (VT) with a right bundle-branch block (RBBB)-type pattern and an R-S
      ratio >1 in lead V1 is difficult with the 12-lead ECG, especially in patients
      with prior apical infarction. METHODS AND RESULTS: We prospectively evaluated 58
      patients with VT. Sixteen patients had apical infarcts (group 1), 29 had
      nonapical infarcts (group 2), and 13 had no heart disease (group 3). QRS complex
      onset to activation at the right ventricular apex (stim-RVA) was measured during
      left ventricular (LV) apical septal and lateral pacing, and 47 RBBB-type VTs (QRS
      RVA) were localized to the septal or lateral apex by using entrainment
      techniques. Pacing and VT site of origin were confirmed by electroanatomic
      mapping. The stim-RVA time was 59+/-16 ms for septal versus 187+/-24 ms for
      lateral sites in group 1, P<0.001; 70+/-14 ms for septal versus 169+/-19 ms for
      lateral sites in group 2, P<0.001; and 42+/-15 ms for septal versus 86+/-16 ms
      for lateral sites in group 3, P<0.005. The QRS-RVA time was 50+/-13 ms for apical
      septal VTs versus 178+/-21 ms for lateral VTs in group 1, P<0.001; 71+/-17 ms for
      apical septal versus 157+/-20 ms for lateral VTs in group 2, P<0.001; and 32+/-12
      ms for septal versus 71+/-16 ms for lateral VTs in group 3, P<0.01. CONCLUSIONS:
      The QRS-RVA differs for the VT site of origin from the LV septal versus lateral
      apex. These data prove useful in rapidly regionalizing the VT site of origin with
      a V1 R-S ratio >1, particularly in instances of an apical infarct, where surface
      ECG distinctions are less identifiable.

PMID- 15492312
TI  - Opposing effects of C-reactive protein isoforms on shear-induced neutrophil
      platelet adhesion and neutrophil aggregation in whole blood.
AB  - BACKGROUND: Plasma C-reactive protein (CRP) level is a powerful predictor of
      cardiovascular events. However, it is not known whether CRP could affect
      neutrophil-platelet adhesion and neutrophil aggregation, key events in acute
      coronary syndromes. Emerging in vitro evidence suggests that some bioactivities
      of CRP are expressed on loss of the pentameric symmetry, resulting in formation
      of modified or monomeric CRP (mCRP). METHODS AND RESULTS: We studied the impact
      of human native CRP and bioengineered mCRP that cannot rearrange into the
      pentameric structure on the kinetics of neutrophil-platelet adhesion and
      neutrophil aggregation in whole blood subjected to shear (approximately 100 s(
      1)) using real-time flow cytometry. Shear resulted in upregulation of platelet P
      selectin expression, leading to platelet capture of neutrophils and subsequent
      neutrophil aggregation, which was dependent on P-selectin, L-selectin, and CD18.
      Native CRP at clinically relevant concentrations markedly attenuated these
      changes. The residual amount of neutrophil adhesion was blocked with anti-CD18 or
      anti-CD11b antibody. By contrast, mCRP concentration-dependently enhanced shear
      induced platelet P-selectin expression and increased the rate and extent of
      formation of both neutrophil-platelet and neutrophil-neutrophil aggregates.
      Complete abrogation of platelet-neutrophil adhesion and neutrophil aggregation
      required both anti-P-selectin and anti-CD18 antibodies but not anti-L-selectin
      antibody. The CRP action was markedly inhibited by an anti-CD32 antibody, whereas
      the mCRP effects were significantly attenuated by an anti-CD16 antibody.
      CONCLUSIONS: These results indicate that native CRP inhibits platelet activation
      and prevents platelet capture of neutrophils, whereas mCRP displays potent
      prothrombotic activities under low levels of shear. Thus, mCRP rather than native
      CRP may precipitate acute coronary syndromes.

PMID- 15492313
TI  - Diagnosis of sleep-related breathing disorders by visual analysis of
      transthoracic impedance signals in pacemakers.
AB  - BACKGROUND: Minute ventilation sensors of cardiac pacemakers measure ventilation
      by means of transthoracic impedance changes between the pacemaker case and the
      electrode tip. We investigated whether this technique might detect sleep-related
      breathing disorders. METHODS AND RESULTS: In 22 patients, analog waveforms of the
      transthoracic impedance signal measured by the pacemaker minute ventilation
      sensor over the course of a night were visualized, scored for apnea/hypopnea
      events, and compared with simultaneous polysomnography. Analysis of transthoracic
      impedance signals correctly identified the presence or absence of moderate to
      severe sleep apnea (apnea/hypopnea index, AHI >20 h(-1)) in all patients
      (receiver operating characteristics, ROC=1.0). The ROC for AHI scores of > or =5
      h(-1) and > or =10 h(-1) showed an area under the curve of 0.95, P<0.005, and
      0.97, P<0.0001, respectively. Accuracy over time assessed by comparing events per
      5-minute epochs was high (Cronbach alpha reliability coefficient, 0.85;
      intraclass correlation, 0.73). Event-by-event comparison within +/-15 seconds
      revealed agreement in 81% (kappa, 0.77; P<0.001). CONCLUSIONS: Detection of
      apnea/hypopnea events by pacemaker minute ventilation sensors is feasible and
      accurate compared with laboratory polysomnography. This technique might be useful
      to screen and monitor sleep-related breathing disorders in pacemaker patients.

PMID- 15492314
TI  - Cardiomyocyte-restricted overexpression of endothelial nitric oxide synthase
      (NOS3) attenuates beta-adrenergic stimulation and reinforces vagal inhibition of
      cardiac contraction.
AB  - BACKGROUND: In the heart, nitric oxide synthases (NOS) modulate cardiac
      contraction in an isoform-specific manner, which is critically dependent on their
      cellular and subcellular localization. Defective NO production by NOS3
      (endothelial NOS [eNOS]) in the failing heart may precipitate cardiac failure,
      which could be reversed by overexpression of NOS3 in the myocardium. METHODS AND
      RESULTS: We studied the influence of NOS3 in relation to its subcellular
      localization on the function of cardiomyocytes isolated from transgenic mice
      overexpressing NOS3 under the alpha-myosin heavy chain promoter (NOS3-TG).
      Immunoblot analysis demonstrated moderate (5-fold) NOS3 overexpression in
      cardiomyocytes from NOS3-TG heterozygotes. Caveolar localization of transgenic
      eNOS was demonstrated by immunofluorescence, coimmunoprecipitation with caveolin
      3, sucrose gradient fractionation, and immunogold staining revealed by electron
      microscopy. Compared with wild-type littermate, contractility of NOS3-TG
      cardiomyocytes analyzed by videomicroscopy revealed a lower incidence of
      spontaneous arrhythmic contractions (n=32, P<0.001); an attenuation of the beta
      adrenergic positive inotropic response (isoproterenol, 10(-7) mol/L: 62.1+/-7.8%
      versus 90.8+/-8.0% of maximum Ca2+ response; n=10 to 17; P<0.05); a potentiation
      of the muscarinic negative chronotropic response (carbamylcholine, 3.10(-8)
      mol/L: -63.9+/-14% versus -27.7+/-5.6% of basal rate; n=8 to 10; P<0.05),
      confirmed by telemetry in vivo; and an attenuation of the accentuated antagonism
      of beta-adrenergically stimulated contraction (-14.6+/-1.5% versus -3.5+/-1.5;
      n=7 to 11; P<0.05). Cardiomyocyte NOS inhibition reversed all 4 effects (P<0.05).
      CONCLUSIONS: Moderate overexpression of NOS3, targeted to caveolae in murine
      cardiomyocytes, potentiates the postsynaptic muscarinic response and attenuates
      the effect of high concentrations of catecholamines. Cardiomyocyte NOS3 may
      represent a promising therapeutic target to restore the sympathovagal balance and
      protect the heart against arrhythmia.

PMID- 15492315
TI  - Sagittal abdominal diameter and risk of sudden death in asymptomatic middle-aged
      men: the Paris Prospective Study I.
AB  - BACKGROUND: Abdominal (visceral) and overall obesity are both related to coronary
      heart disease mortality risk; however, the relative contribution of these 2
      components of fat deposit in the etiology of sudden death is unknown. METHODS AND
      RESULTS: We used the data from 7079 asymptomatic men of the Paris Prospective
      Study I who were free of ischemic heart disease and who were 43 to 52 years of
      age at first clinical examination between 1967 and 1972. Body mass index (BMI)
      and sagittal abdominal diameter (SAD) were measured at baseline and used as
      markers of overall and abdominal obesity. During a follow-up of 23 years, there
      were 118 sudden deaths and 192 fatal myocardial infarctions. After adjustment for
      baseline level of cardiovascular risk factors, trunk subcutaneous fat, and
      thoracic diameter, the ratio of the fifth over the first quintile of SAD was 2.6
      (95% CI 1.0 to 6.7) and 2. 6 (95% CI 1.3 to 5.1) for sudden death and fatal
      myocardial infarction, respectively, and the risk of sudden death increased
      proportionally with SAD level. The corresponding ratios for BMI were 2.0 (95% CI
      1.1 to 3.8) and 1.0 (95% CI 0.6 to 1.7), respectively. Compared with men with low
      SAD (first tertile) and normal BMI (<25 kg/m2), men with elevated SAD (third
      tertile) were at increased risk of sudden death but not of fatal myocardial
      infarction, whether they were of normal weight (multivariate adjusted relative
      risk 3. 0 [95% CI 1.3 to 6. 9]) or overweight (BMI > or =25 kg/m2; 1.9 [95% CI
      1.0 to 3.9]). CONCLUSIONS: In asymptomatic French middle-aged men, larger SAD was
      associated with a particularly increased risk of sudden death, independent of BMI
      level and known cardiovascular risk factors.

PMID- 15492316
TI  - Left ventricular mass in relation to genetic variation in angiotensin II
      receptors, renin system genes, and sodium excretion.
AB  - BACKGROUND: In the European Project On Genes in Hypertension (EPOGH), we
      investigated in 3 populations to what extent left ventricular mass (LVM) was
      associated with genetic variation in the angiotensin II receptors type 1 (AGTR1
      A1166C) and type 2 (AGTR2 G1675A) while accounting for possible gene-gene
      interactions with the angiotensin-converting enzyme (ACE D/I) and angiotensinogen
      (AGT -532C/T) polymorphisms. METHODS AND RESULTS: We randomly recruited 221
      nuclear families (384 parents, 431 offspring) in Cracow (Poland), Novosibirsk
      (Russia), and Mirano (Italy). Echocardiographic LVM was indexed to body surface
      area, adjusted for covariates, and subjected to multivariate analyses using
      generalized estimating equations and quantitative transmission disequilibrium
      tests in a population-based and family-based approach, respectively. For AGTR1
      and AGTR2, there was no heterogeneity in the phenotype-genotype relations across
      populations. LVM index was unrelated to the AGTR1 A1166C polymorphism. In men, in
      the population- and family-based analyses, the allelic effects of the AGTR2
      polymorphism on LVM index differed (P=0.01) according to sodium excretion. In
      women, this gene-environment interaction did not reach statistical significance.
      In untreated men, LVM index (4.2 g/m2 per 100 mmol) and left ventricular internal
      diameter (0.73 mm/100 mmol) increased (P<0.02) with higher sodium excretion in
      the presence of the G allele with an opposite tendency in A allele carriers. The
      ACE D/I polymorphism, together with the ACE genotype-by-sodium interaction term,
      significantly and independently improved the models relating LVM index to the
      AGTR2 polymorphism and the AGTR2 genotype-by-sodium interaction. CONCLUSIONS: The
      present findings support the hypothesis that in men the AGTR2 G1675A and the ACE
      D/I polymorphisms independently influence LVM and that salt intake modulates
      these genetic effects.

PMID- 15492317
TI  - Heritability of ambulatory heart rate variability.
AB  - BACKGROUND: Reduced heart rate variability (HRV) is a prognostic factor for
      cardiac disease and cardiac mortality. Understanding the sources of individual
      differences in HRV may increase its diagnostic use and provide new angles for
      preventive therapy. To date, the contribution of genetic and environmental
      factors to the variance in HRV has not been investigated during prolonged periods
      of ambulatory monitoring in a naturalistic setting. METHODS AND RESULTS: In 772
      healthy twins and singleton siblings, ambulatory ECG was recorded during 24
      hours. Two time domain measures of HRV were used: the standard deviations of all
      normal-to-normal intervals across 5-minute segments (SDNN index) and the root
      mean square of successive differences between adjacent normal RR intervals
      (RMSSD). Multivariate genetic analyses across 4 periods of day (morning,
      afternoon, evening, night) yielded significant estimates for genetic contribution
      to the mean ambulatory SDNN index (ranging from 35% to 47%) and the mean
      ambulatory RMSSD (ranging from 40% to 48%). CONCLUSIONS: Ambulatory HRV measures
      are highly heritable traits that can be used to support genetic association and
      linkage studies in their search for genetic variation influencing cardiovascular
      disease risk.

PMID- 15492318
TI  - Multivariate assessment of lipid parameters as predictors of coronary heart
      disease among postmenopausal women: potential implications for clinical
      guidelines.
AB  - BACKGROUND: Over the past decade, lipid measurements have been significantly
      improved and standardized. We evaluated the usefulness of multiple plasma lipid
      parameters in predicting coronary heart diseases (CHD) among women. METHODS AND
      RESULTS: Among 32,826 women from the Nurses' Health Study who provided blood
      samples at baseline, 234 CHD events were documented during 8 years of follow-up.
      In a nested study, these cases were matched to controls (1:2) for age, smoking,
      fasting status, and month of blood draw. We estimated the relative risk (RR) for
      each lipid parameter, adjusted for C-reactive protein, homocysteine, body mass
      index, family history, hypertension, diabetes, postmenopausal hormone use,
      physical activity, alcohol intake, and blood draw parameters. The RRs associated
      with an increase of approximately 1 SD (mg/dL) were as follows: HDL cholesterol
      (HDL-C) (RR=0.6 [0.5 to 0.8], SD=17), apolipoprotein B100 (apoB100) (RR=1.7 [1.4
      to 2.1], SD=32), LDL cholesterol (LDL-C) (RR=1.4 [1.1 to 1.7], SD=36), total
      cholesterol (TC) (RR=1.4 [1.1 to 1.6], SD=40), and triglycerides (RR=1.3 [1.0 to
      1.5], SD=80). Among the lipid indexes, the RRs were: apoB100/HDL-C (RR=1.7 [1.4
      to 2.1], SD=1.0), TC/HDL-C (RR=1.6 [1.3 to 1.9], SD=1.3), LDL-C/HDL-C (RR=1.5
      [1.3 to 1.9], SD=1.0), and non-HDL-C (RR=1.6 [1.3 to 1.9], SD=42 mg/dL). After
      simultaneous control for several lipid biomarkers, HDL-C was the primary
      contributor of the variation in multivariate models (P=0.01), followed by LDL-C
      (P=0.01), whereas triglycerides and apoB100 did not contribute further
      information. HDL-C-related ratios were the strongest contributors to predicting
      CHD (P<0.0001). CONCLUSIONS: Lower levels of HDL-C may be a key discriminator of
      higher CHD events among postmenopausal women. HDL-C-related ratios (such as
      TC/HDL-C) provide a powerful predictive tool independently of other known CHD
      risk factors.

PMID- 15492319
TI  - Cellular physiology of cholesterol efflux in vascular endothelial cells.
AB  - BACKGROUND: Of the cells that compose the atherosclerotic plaque, vascular
      endothelial cells are the most resistant to cholesterol accumulation. Cholesterol
      efflux pathways may play an important role in endothelial cholesterol
      homeostasis. METHODS AND RESULTS: We examined the global genetic response of
      endothelial cells to cholesterol and in particular the contribution of the
      cholesterol efflux proteins ATP-binding cassette transporter A1 (ABCA1), ATP
      binding cassette transporter G1 (ABCG1), and scavenger receptor B-I (SR-BI) to
      endothelial cell cholesterol efflux. The ABCG1 gene is induced in endothelial
      cells by cholesterol, whereas ABCA1 is not. Using specific chemical inhibitors of
      ABC transporters and SR-BI, we have shown that neither ABC transporters nor SR-BI
      is required for apolipoprotein A-1-mediated endothelial cholesterol efflux.
      CONCLUSIONS: Endothelial cells may use nontraditional pathways for cholesterol
      efflux.

PMID- 15492320
TI  - Intravascular thrombosis after hypoxia-induced pulmonary hypertension: regulation
      by cyclooxygenase-2.
AB  - BACKGROUND: Pulmonary hypertension induced by chronic hypoxia is characterized by
      thickening of pulmonary artery walls, elevated pulmonary vascular resistance, and
      right-heart failure. Prostacyclin analogues reduce pulmonary pressures in this
      condition; raising the possibility that cycloxygenase-2 (COX-2) modulates the
      response of the pulmonary vasculature to hypoxia. METHODS AND RESULTS: Sprague
      Dawley rats in which pulmonary hypertension was induced by hypobaric hypoxia for
      14 days were treated concurrently with the selective COX-2 inhibitor SC236 or
      vehicle. Mean pulmonary arterial pressure (mPAP) was elevated after hypoxia
      (28.1+/-3.2 versus 17.2+/-3.1 mm Hg; n=8, P<0.01), with thickening of small
      pulmonary arteries and increased COX-2 expression and prostacyclin formation.
      Selective inhibition of COX-2 aggravated the increase in mPAP (42.8+/-5.9 mm Hg;
      n=8, P<0.05), an effect that was attenuated by the thromboxane (TX)
      A2/prostaglandin endoperoxide receptor antagonist ifetroban. Urinary TXB2
      increased during hypoxia (5.9+/-0.9 versus 1.2+/-0.2 ng/mg creatinine; n=6,
      P<0.01) and was further increased by COX-2 inhibition (8.5+/-0.7 ng/mg
      creatinine; n=6, P< 0.05). In contrast, urinary excretion of the prostacyclin
      metabolite 6-ketoprostaglandin F1alpha decreased with COX-2 inhibition (8.6+/-3.0
      versus 27.0+/-4.8 ng/mg creatinine; n=6, P< 0.05). Platelet activation was
      enhanced after chronic hypoxia. COX-2 inhibition further reduced the PFA-100
      closure time and enhanced platelet deposition in the smaller pulmonary arteries,
      effects that were attenuated by ifetroban. Mice with targeted disruption of the
      COX-2 gene exposed to chronic hypoxia had exacerbated right ventricular end
      systolic pressure, whereas targeted disruption of COX-1 had no effect.
      CONCLUSIONS: COX-2 expression is increased and regulates platelet activity and
      intravascular thrombosis in hypoxia-induced pulmonary hypertension.

PMID- 15492321
TI  - Pressure overload induces cardiac dysfunction and dilation in signal transducer
      and activator of transcription 6-deficient mice.
AB  - BACKGROUND: Signal transducer and activator of transcription (STAT) proteins
      constitute a family of transcription factors that mediate many cytokine-induced
      responses. STAT6 is activated by angiotensin II and in rat hypertrophied hearts
      and in human hearts with dilated cardiomyopathy. This suggests that STAT6 may be
      involved in the pathogenesis of cardiac hypertrophy and heart failure. For this
      study we used STAT6-deficient (STAT6-/-) mice to examine the in vivo role of
      STAT6. METHODS AND RESULTS: STAT6-/- hearts showed no morphological,
      histological, or functional defects. We examined left ventricular structural and
      functional remodeling 1 week after thoracic transverse aortic constriction (TAC).
      Western blot and immunohistochemical analyses showed increased STAT6 activity
      after TAC in the heart of wild-type mice. STAT6-/- mice showed a significant
      increase in end-diastolic left ventricular internal dimension accompanied by
      impaired contractility compared with wild-type mice but no differences in
      hypertrophic parameters. The number of terminal deoxynucleotidyl transferase
      mediated biotin dUTP nick-end labeling-positive myocytes after TAC had increased
      in STAT6-/- compared with wild-type mice. Prolonged induction of tumor necrosis
      factor-alpha (TNF-alpha) mRNA was observed in STAT6-/- hearts, whereas TNF-alpha
      mRNA was only transiently induced in wild-type mice. Tristetraprolin was induced
      after TAC in wild-type mice but not in STAT6-/- mice. Tristetraprolin reporter
      assay with the use of isolated neonatal cardiomyocyte indicated that the promoter
      was significantly activated by endothelin-1 in wild-type but not in STAT6-/-
      cardiomyocytes. The lack of promoter activation by endothelin-1 in STAT6-/-
      cardiomyocytes was rescued by forced expression of STAT6. CONCLUSIONS: STAT6
      plays a protective role against hemodynamic stress in hearts.

PMID- 15492322
TI  - Effects of fosinopril and pravastatin on cardiovascular events in subjects with
      microalbuminuria.
AB  - BACKGROUND: Microalbuminuria is associated with increased risk of cardiovascular
      events. We assessed whether therapeutic intervention aimed at lowering urinary
      albumin excretion would reduce cardiovascular events in microalbuminuric subjects
      (15 to 300 mg/24 hours). METHODS AND RESULTS: From the Prevention of Renal and
      Vascular Endstage Disease (PREVEND) cohort (n=8592), 1439 subjects fulfilled the
      inclusion criteria of the PREVEND Intervention Trial (PREVEND IT). Of these
      subjects, 864 were randomized to fosinopril 20 mg or matching placebo and to
      pravastatin 40 mg or matching placebo. The mean follow-up was 46 months, and the
      primary end point was cardiovascular mortality and hospitalization for
      cardiovascular morbidity. Mean age was 51+/-12 years; 65% of subjects were male,
      and 3.4% had a previous cardiovascular event. Mean cholesterol level was 5.8+/
      1.0 mmol/L, mean systolic/diastolic blood pressure was 130+/-18/76+/-10 mm Hg,
      and median urinary albumin excretion was 22.8 (15.8 to 41.3) mg/24 hours. The
      primary end point occurred in 45 subjects (5.2%). Fosinopril reduced urinary
      albumin excretion by 26% (P<0.001). Subjects treated with fosinopril showed a 40%
      lower incidence of the primary end point (hazard ratio 0.60 [95% CI 0.33 to
      1.10], P=0.098, log-rank). Pravastatin did not reduce urinary albumin excretion,
      and subjects treated with pravastatin showed a 13% lower incidence of the primary
      end point than subjects in the placebo group (0.87 [0.49 to 1.57], P=0.649, log
      rank). CONCLUSIONS: In microalbuminuric subjects, treatment with fosinopril had a
      significant effect on urinary albumin excretion. In addition, fosinopril
      treatment was associated with a trend in reducing cardiovascular events.
      Treatment with pravastatin did not result in a significant reduction in urinary
      albumin excretion or cardiovascular events.

PMID- 15492323
TI  - L-type Ca2+ current downregulation in chronic human atrial fibrillation is
      associated with increased activity of protein phosphatases.
AB  - BACKGROUND: Although downregulation of L-type Ca2+ current (I(Ca,L)) in chronic
      atrial fibrillation (AF) is an important determinant of electrical remodeling,
      the molecular mechanisms are not fully understood. Here, we tested whether
      reduced I(Ca,L) in AF is associated with alterations in phosphorylation-dependent
      channel regulation. METHODS AND RESULTS: We used whole-cell voltage-clamp
      technique and biochemical assays to study regulation and expression of I(Ca,L) in
      myocytes and atrial tissue from 148 patients with sinus rhythm (SR) and chronic
      AF. Basal I(Ca,L) at +10 mV was smaller in AF than in SR (-3.8+/-0.3 pA/pF,
      n=138/37 [myocytes/patients] and -7.6+/-0.4 pA/pF, n=276/86, respectively;
      P<0.001), though protein levels of the pore-forming alpha1c and regulatory beta2a
      channel subunits were not different. In both groups, norepinephrine (0.01 to 10
      micromol/L) increased I(Ca,L) with a similar maximum effect and comparable
      potency. Selective blockers of kinases revealed that basal I(Ca,L) was enhanced
      by Ca2+/calmodulin-dependent protein kinase II in SR but not in AF.
      Norepinephrine-activated I(Ca,L) was larger with protein kinase C block in SR
      only, suggesting decreased channel phosphorylation in AF. The type 1 and type 2A
      phosphatase inhibitor okadaic acid increased basal I(Ca,L) more effectively in AF
      than in SR, which was compatible with increased type 2A phosphatase but not type
      1 phosphatase protein expression and higher phosphatase activity in AF.
      CONCLUSIONS: In AF, increased protein phosphatase activity contributes to
      impaired basal I(Ca,L). We propose that protein phosphatases may be potential
      therapeutic targets for AF treatment.

PMID- 15492324
TI  - Cardiology patient pages. Prevention of deep vein thrombosis and pulmonary
      embolism.

PMID- 15492325
TI  - Images in cardiovascular medicine. Thrombosis of a coronary artery aneurysm in a
      young man presenting with acute myocardial infarction.

PMID- 15492326
TI  - Images in cardiovascular medicine. Hypertrophic cardiomyopathy with apical
      aneurysm.

PMID- 15492327
TI  - Ethics and professionalism: can there be consensus? An editorial comment on the
      report of the ACCF/AHA Consensus Conference on Professionalism and Ethics.

PMID- 15492328
TI  - Stopping statins.

PMID- 15492329
TI  - The role of vascular endothelial growth factor in restenosis: the controversy
      continues.

PMID- 15492330
TI  - Preclinical evaluation of drug-eluting stents for peripheral applications:
      recommendations from an expert consensus group.

PMID- 15492331
TI  - ACCF/AHA consensus conference report on professionalism and ethics.

PMID- 15492332
TI  - Summaries for patients. Breast cancer in women who survived childhood cancer.

PMID- 15492333
TI  - Summaries for patients. Effectiveness of nurse-delivered instruction in special
      exercises for patients with chronic dizziness.

PMID- 15492334
TI  - Summaries for patients. Nurse care management for low-risk patients with heart
      failure.

PMID- 15492335
TI  - Summaries for patients. Treating men with chronic prostatitis/chronic pelvic pain
      syndrome.

PMID- 15492336
TI  - Inhaled corticosteroids and adrenal function.

PMID- 15492337
TI  - Ciprofloxacin or tamsulosin in men with chronic prostatitis/chronic pelvic pain
      syndrome: a randomized, double-blind trial.
AB  - BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in men is
      principally defined by pain in the pelvic region lasting more than 3 months. No
      cause of the disease has been established, and therapies are empirical and mostly
      untested. Antimicrobial agents and alpha-adrenergic receptor blockers are
      frequently used. OBJECTIVE: To determine whether 6-week therapy with
      ciprofloxacin or tamsulosin is more effective than placebo at improving symptoms
      in men with refractory, long-standing CP/CPPS. DESIGN: Randomized, double-blind
      trial with a 2 x 2 factorial design comparing 6 weeks of therapy with
      ciprofloxacin, tamsulosin, both drugs, or placebo. SETTING: Urology outpatient
      clinics at 10 tertiary care medical centers in North America. PATIENTS: Patients
      were identified from referral-based practices of urologists. One hundred ninety
      six men with a National Institutes of Health Chronic Prostatitis Symptom Index
      (NIH-CPSI) score of at least 15 and a mean of 6.2 years of symptoms were
      enrolled. Patients had received substantial previous treatment. MEASUREMENTS: The
      authors evaluated NIH-CPSI total score and subscores, patient-reported global
      response assessment, a generic measure of quality of life, and adverse events.
      INTERVENTIONS: Ciprofloxacin, 500 mg twice daily; tamsulosin, 0.4 mg once daily;
      a combination of the 2 drugs; or placebo. RESULTS: The NIH-CPSI total score
      decreased modestly in all treatment groups. No statistically significant
      difference in the primary outcome was seen for ciprofloxacin versus no
      ciprofloxacin (P = 0.15) or tamsulosin versus no tamsulosin (P > 0.2). Treatments
      also did not differ significantly for any of the secondary outcomes. LIMITATIONS:
      Treatment lasting longer than 6 weeks was not tested. Patients who had received
      less pretreatment may have responded differently. CONCLUSION: Ciprofloxacin and
      tamsulosin did not substantially reduce symptoms in men with long-standing
      CP/CPPS who had at least moderate symptoms.

PMID- 15492338
TI  - Breast cancer after childhood cancer: a report from the Childhood Cancer Survivor
      Study.
AB  - BACKGROUND: Survivors of childhood cancer are at risk for secondary breast
      cancer. Other than previous chest radiation therapy, risk factors for secondary
      breast cancer have not been established. OBJECTIVE: To identify risk factors for
      breast cancer among female survivors of childhood cancer. DESIGN: Retrospective
      cohort study. SETTING: The Childhood Cancer Survivor Study (CCSS), a multicenter
      study of persons who survived more than 5 years after childhood cancer diagnosed
      from 1970 to 1986. PARTICIPANTS: Among 6068 women in the CCSS, 95 women had 111
      confirmed cases of breast cancer. MEASUREMENTS: Standardized incidence ratios for
      breast cancer were calculated by using age-specific incidence rates in the
      general population. Breast cancer incidence was evaluated with respect to primary
      cancer diagnosis and therapy, age at and time since primary diagnosis, menstrual
      and reproductive history, and family history of cancer. RESULTS: Breast cancer
      risk was increased in survivors who were treated with chest radiation therapy
      (standardized incidence ratio, 24.7 [95% CI, 19.3 to 31.0]) and survivors of bone
      and soft-tissue sarcoma who were not treated with chest radiation therapy
      (standardized incidence ratios, 6.7 and 7.6, respectively). Family history of
      breast cancer (relative rate, 2.7 [CI, 1.3 to 5.0]) and history of thyroid
      disease (relative rate, 1.7 [CI, 1.1 to 2.6]) were independently associated with
      increased risk, and exposure to pelvic radiation was protective (relative rate,
      0.6 [CI, 0.4 to 0.9]). Age at primary cancer diagnosis and menstrual and
      reproductive histories did not statistically significantly modify risk.
      LIMITATIONS: This cohort has not yet attained an age at which breast cancer risk
      is greatest. CONCLUSION: Survivors of childhood sarcomas and those who received
      chest radiation therapy are at risk for secondary breast cancer. When assessing a
      survivor's risk, clinicians should consider primary diagnosis, previous radiation
      therapy, family cancer history, and history of thyroid disease.

PMID- 15492339
TI  - Effectiveness of primary care-based vestibular rehabilitation for chronic
      dizziness.
AB  - BACKGROUND: Dizziness is a very common symptom and is usually managed in primary
      care. Vestibular rehabilitation for dizziness is a simple treatment that may be
      suitable for primary care delivery, but its effectiveness has not yet been
      determined. OBJECTIVE: To evaluate the effectiveness of nurse-delivered
      vestibular rehabilitation in primary care for patients with chronic dizziness.
      DESIGN: Single-blind randomized, controlled trial. SETTING: 20 general practices
      in southern England. PATIENTS: 170 adult patients with chronic dizziness who were
      randomly assigned to vestibular rehabilitation (n = 83) or usual medical care (n
      = 87). INTERVENTION: Each patient received one 30- to 40-minute appointment with
      a primary care nurse. The nurse taught the patient exercises to be carried out
      daily at home, with the support of a treatment booklet. MEASUREMENTS: Primary
      outcome measures were baseline, 3-month, and 6-month assessment of self-reported
      spontaneous and provoked symptoms of dizziness, dizziness-related quality of
      life, and objective measurement of postural stability with eyes open and eyes
      closed. RESULTS: At 3 months, improvement on all primary outcome measures in the
      vestibular rehabilitation group was significantly greater than in the usual
      medical care group; this improvement was maintained at 6 months. Of 83 treated
      patients, 56 (67%) reported clinically significant improvement compared with 33
      of 87 (38%) usual care patients (relative risk, 1.78 [95% CI, 1.31 to 2.42]).
      LIMITATIONS: Psychological elements of the therapy may have contributed to
      outcomes, and the treatment may be effective only for well-motivated patients.
      CONCLUSIONS: Vestibular rehabilitation delivered by nurses in general practice
      improves symptoms, postural stability, and dizziness-related handicap in patients
      with chronic dizziness.

PMID- 15492340
TI  - Care management for low-risk patients with heart failure: a randomized,
      controlled trial.
AB  - BACKGROUND: Nurse care management programs for patients with chronic illness have
      been shown to be safe and effective. OBJECTIVE: To determine whether a telephone
      mediated nurse care management program for heart failure reduced the rate of
      rehospitalization for heart failure and for all causes over a 1-year period.
      DESIGN: Randomized, controlled trial of usual care with nurse management versus
      usual care alone in patients hospitalized for heart failure from May 1998 through
      October 2001. SETTING: 5 northern California hospitals in a large health
      maintenance organization. PATIENTS: Of 2786 patients screened, 462 met clinical
      criteria for heart failure and were randomly assigned (228 to intervention and
      234 to usual care). INTERVENTION: Nurse care management provided structured
      telephone surveillance and treatment for heart failure and coordination of
      patients' care with primary care physicians. MEASUREMENTS: Time to first
      rehospitalization for heart failure or for any cause and time to a combined end
      point of first rehospitalization, emergency department visit, or death. RESULTS:
      At 1 year, half of the patients had been rehospitalized at least once and 11% had
      died. Only one third of rehospitalizations were for heart failure. The rate of
      first rehospitalization for heart failure was similar in both groups
      (proportional hazard, 0.85 [95% CI, 0.46 to 1.57]). The rate of all-cause
      rehospitalization was similar (proportional hazard, 0.98 [CI, 0.76 to 1.27]).
      LIMITATIONS: The findings of this study, conducted in a single health care
      system, may not be generalizable to other health care systems. The overall effect
      of the intervention was minor. CONCLUSIONS: Among patients with heart failure at
      low risk on the basis of sociodemographic and medical attributes, nurse care
      management did not statistically significantly reduce rehospitalizations for
      heart failure or for any cause. Such programs may be less effective for patients
      at low risk than those at high risk.

PMID- 15492341
TI  - Systematic review: antihypertensive drug therapy in black patients.
AB  - BACKGROUND: Hypertension occurs more frequently and is generally more severe in
      black persons than in white persons, leading to excess morbidity and mortality.
      PURPOSE: To systematically review the efficacy of different antihypertensive
      drugs in reducing blood pressure, morbidity, and mortality in hypertensive black
      adults. DATA SOURCES: The following databases were searched from their inception
      through November 2003: MEDLINE, EMBASE, LILACS (Literatura Latino-Americana y del
      Caribe en Ciencias de la Salud), African Index Medicus, and the Cochrane Library.
      PubMed was also searched from September 2003 through March 2004. Searches were
      conducted without language restriction. STUDY SELECTION: Randomized, controlled
      trials of drugs versus placebo (blood pressure outcomes) or drugs versus placebo
      or other drugs (morbidity and mortality outcomes). DATA EXTRACTION: 2 reviewers
      independently extracted data. DATA SYNTHESIS: The efficacy of beta-blockers in
      reducing systolic blood pressure and the efficacy of angiotensin-converting
      enzyme inhibitors in achieving diastolic blood pressure goals did not
      significantly differ from that of placebo (weighted mean difference for beta
      blockers, -3.53 mm Hg [95% CI, -7.51 to 0.45 mm Hg]; relative risk for
      angiotensin-converting enzyme inhibitors, 1.35 [CI, 0.81 to 2.26]). In the pooled
      analyses, other reviewed drugs (calcium-channel blockers, diuretics, central
      sympatholytics, alpha-blockers, and angiotensin II receptor blockers) were more
      effective than placebo in reducing blood pressure, but only calcium-channel
      blockers remained effective in all prespecified subgroups, including patients
      with a baseline diastolic blood pressure of 110 mm Hg or greater. Main morbidity
      and mortality outcomes did not differ significantly between treatment groups when
      drugs were combined to reach blood pressure goals. However, trial results
      indicated a greater occurrence of diabetes with diuretics and a higher risk for
      cardiovascular events with drug regimens that included angiotensin-converting
      enzyme inhibitors. LIMITATIONS: This meta-analysis evaluated the blood pressure
      lowering-efficacy of monotherapy only. CONCLUSIONS: Drugs differ in their
      efficacy for reducing blood pressure in black patients, but there is no solid
      evidence that efficacy for reducing morbidity and mortality outcomes differs once
      patients achieve the blood pressure goal.

PMID- 15492342
TI  - Update in cardiology.

PMID- 15492343
TI  - Differences, disparities, and biases: clarifying racial variations in health care
      use.
AB  - Studies documenting racial differences in health care use are common in the
      medical literature. However, observational studies of racial differences in
      health care use lack a framework for interpreting reports of variations in health
      care use, leading to various terms, ranging from "variations" to "bias," that
      suggest different causes, consequences, and, ultimately, remedies for such
      variations in treatment. We propose criteria to assess racial differences in
      health care use by using a clinical equity (equal treatment based on equal
      clinical need) framework. This framework differentiates between initial reports
      of racial differences and subsequent classifications of their findings as racial
      disparities or racial bias in health care use. Racial variations in health care
      use may be considered disparities after demonstrating that racial differences are
      not attributable to treatment eligibility, clinical contraindications, patient
      preferences, or confounding by other clinical factors and are associated with
      adverse consequences. Racial bias with adverse consequences in health care may be
      inferred if a racial variation in treatment that has been characterized as a
      disparity persists after accounting for health care system factors (for example,
      type of hospital at which the patient was treated). We apply this framework to
      published reports of racial differences in treatment to determine which studies
      provide evidence of differences, disparities, and bias. We discuss the use of
      such a framework in directing policy interventions for alleviating inappropriate
      racial variations in health care use.

PMID- 15492344
TI  - Treating chronic prostatitis: antibiotics no, alpha-blockers maybe.

PMID- 15492345
TI  - Easy, inexpensive, and effective: vestibular exercises for balance control.

PMID- 15492346
TI  - Deconstructing heart failure disease management.

PMID- 15492347
TI  - Shower time.

PMID- 15492348
TI  - Limitations of gold standards for diagnosing gastroesophageal reflux disease.

PMID- 15492349
TI  - Hand hygiene.

PMID- 15492350
TI  - Screening for lung cancer.

PMID- 15492351
TI  - Ezetimibe and statin-associated myopathy.

PMID- 15492352
TI  - Senna-induced hepatitis in a poor metabolizer.

PMID- 15492353
TI  - Risperidone in the treatment of disruptive behavioral symptoms in children with
      autistic and other pervasive developmental disorders.
AB  - OBJECTIVE: To investigate the efficacy and safety of risperidone for the
      treatment of disruptive behavioral symptoms in children with autism and other
      pervasive developmental disorders (PDD). METHODS: In this 8-week, randomized,
      double-blind, placebo-controlled trial, risperidone/placebo solution (0.01-0.06
      mg/kg/day) was administered to 79 children who were aged 5 to 12 years and had
      PDD. Behavioral symptoms were assessed using the Aberrant Behavior Checklist
      (ABC), Nisonger Child Behavior Rating Form, and Clinical Global Impression
      Change. Safety assessments included vital signs, electrocardiogram,
      extrapyramidal symptoms, adverse events, and laboratory tests. RESULTS: Subjects
      who were taking risperidone (mean dosage: 0.04 mg/kg/day; 1.17 mg/day)
      experienced a significantly greater mean decrease on the irritability subscale of
      the ABC (primary endpoint) compared with those who were taking placebo. By study
      endpoint, risperidone-treated subjects exhibited a 64% improvement over baseline
      in the irritability score almost double that of placebo-treated subjects (31%).
      Risperidone-treated subjects also exhibited significantly greater decreases on
      the other 4 subscales of the ABC; on the conduct problem, insecure/anxious,
      hyperactive, and overly sensitive subscales of the Nisonger Child Behavior Rating
      Form (parent version); and on the Visual Analog Scale of the most troublesome
      symptom. More risperidone-treated subjects (87%) showed global improvement in
      their condition compared with the placebo group (40%). Somnolence, the most
      frequently reported adverse event, was noted in 72.5% versus 7.7% of subjects
      (risperidone vs placebo) and seemed manageable with dose/dose-schedule
      modification. Risperidone-treated subjects experienced statistically
      significantly greater increases in weight (2.7 vs 1.0 kg), pulse rate, and
      systolic blood pressure. Extrapyramidal symptoms scores were comparable between
      groups. CONCLUSIONS: Risperidone was well tolerated and efficacious in treating
      behavioral symptoms associated with PDD in children.

PMID- 15492354
TI  - Prediction of IQ and achievement at age 8 years from neurodevelopmental status at
      age 1 year in children with D-transposition of the great arteries.
AB  - OBJECTIVE: Studies of developmental outcomes in children with congenital heart
      disease (CHD) frequently use assessments conducted in infancy as primary
      endpoints. Whether test scores of CHD patients in infancy are predictive of
      status at school age has not been evaluated, however. METHODS: In the Boston
      Circulatory Arrest Study, 135 children with D-transposition of the great arteries
      repaired by arterial switch operation were administered the Bayley Scales of
      Infant Development and the Fagan Test of Infant Intelligence at 1 year of age and
      the Wechsler Intelligence Scale for Children, Third Edition and the Wechsler
      Individual Achievement Test at 8 years. RESULTS: Although most 1-year test scores
      were significantly associated with 8-year test scores, the amounts of shared
      variance were modest (<10%). All 1-year test scores had poor sensitivity (16%
      32%) and poor positive predictive value (35%-42%) but good specificity (80%-93%)
      and negative predictive value (78%-79%). More than half of the children with low
      scores at 8 years (< or =85) had had scores >84 at 1 year. CONCLUSION: This
      pattern suggests that although test scores at 1 year are modestly associated with
      test scores at 8 years, many children who are at risk for poor late outcomes will
      not be identified on the basis of 1-year test scores. Long-term follow-up of
      children with CHD is necessary to draw inferences about the developmental
      sequelae of preoperative, intraoperative, and postoperative factors.

PMID- 15492355
TI  - Neurotoxicities in infants seen with the consumption of star anise tea.
AB  - Chinese star anise (Illicium verum Hook f.) is a well-known spice used in many
      cultures. Many populations use it as a treatment for infant colic. Japanese star
      anise (Illicium anisatum L), however, has been documented to have both neurologic
      and gastrointestinal toxicities. Recently, concern has been raised regarding the
      adulteration of Chinese star anise with Japanese star anise. We report 7 cases of
      adverse neurologic reactions in infants seen with the home administration of star
      anise tea. In addition, we have found evidence that Chinese star anise has been
      contaminated with Japanese star anise. More strict federal regulation of the
      import of star anise into the United States is warranted. Star anise tea should
      no longer be administered to infants because of its potential danger in this
      population.

PMID- 15492356
TI  - Two-year clinical and immune outcomes in human immunodeficiency virus-infected
      children who reconstitute CD4 T cells without control of viral replication after
      combination antiretroviral therapy.
AB  - OBJECTIVE: To evaluate 96-week clinical and immune outcomes to protease inhibitor
      containing antiretroviral therapy. METHODS: A prospective study was conducted of
      40 human immunodeficiency virus (HIV)-infected children who displayed viral
      suppression (VS) with successful immune reconstitution (IS), failure to suppress
      virus (VF) or develop immune reconstitution (IF), or discordant immune and viral
      responses (VF/IS) at 24 weeks posttherapy. All children enrolled had viral RNA
      >4.0 log10 copies per mL and were Centers for Disease Control ad Prevention
      immune stage 2 or 3. Clinical, viral, and immune outcomes were assessed during
      the subsequent 72 weeks. RESULTS: VS/IS and VF/IS groups displayed similar
      sustained increases in CD4 T cells, although viral levels rebounded by 48 and 96
      weeks posttherapy to pretherapy levels in the discordant group. The VF/IS outcome
      group had significant increases in height and weight z scores compared with entry
      and were similar to the VS/IS group. After treatment, antigen-specific responses
      after tetanus immunization were similar in the VF/IS and VS/IS groups. Prevalence
      of HIV-associated illnesses decreased in both VS/IS and VF/IS but not in VF/IF
      response groups. CONCLUSIONS: The findings indicate that viral replication under
      the selective pressure of protease inhibitors fails to exhibit the same
      deleterious impact on T-cell immunity as pretherapy viruses. CD4 T-cell counts
      may be a better predictor of disease progression and improvement in growth than
      viral burden in HIV-infected children who receive a protease inhibitor as part of
      a highly active antiretroviral therapy regimen.

PMID- 15492357
TI  - Spinal muscular atrophy: survival pattern and functional status.
AB  - OBJECTIVE: Spinal muscular atrophy (SMA) is common. The prevalence of SMA in
      southern Chinese is 1 in 53,000. The clinical course is variable. The traditional
      classification of SMA includes age of onset, age of death, achievement of motor
      milestones, and ambulatory status as criteria. There was a lack of inclusion of
      the best lifetime functional status of any child with SMA. With the advances in
      medical care, the life expectancy and ambulatory status of patients with SMA have
      improved. The objective of this study was to assess the survival pattern,
      ambulatory status, and functional status of children with SMA. METHODS: Patients
      with SMA were recruited from the neuromuscular clinic of the Duchess of Kent
      Children's Hospital, which is a university-affiliated hospital, and the Families
      of SMA in Hong Kong. By September 2002, 102 SMA cases had been registered in the
      Duchess of Kent Children's Hospital neuromuscular clinic and Families of SMA
      registry, and 83 patients were analyzed. Among them, 39 were recruited for the
      administration of Functional Independence Measure for Children (WeeFIM), an
      assessment tool for functional status that has been previously validated by us
      for Chinese children. The diagnosis of SMA was made from clinical history, serum
      muscle enzyme, electromyography, muscle biopsy, and, recently, by molecular
      studies. In Hong Kong, molecular tests of the survivor motor neuron gene was
      available since 1995. A total of 36 in our cohort of 83 patients had the
      diagnosis confirmed with molecular analyses. We adopted the classification of SMA
      from previous studies in which the criteria were based on the International SMA
      consortium (1992) with modifications according to the 59th European Neuromuscular
      Center International Workshops. As only SMA patients with childhood onset were
      studied, we did not include any type IV patients in our study. Parents were
      interviewed and records were reviewed for demographic and clinical data,
      including age of onset, gender, family history, motor milestones, disease
      progression, loss of motor function, and involvement of respiratory or bulbar
      muscles. We define the age of disease onset as the age in which the first
      abnormalities were obvious from the medical records or from the descriptions of
      the parents about the first signs of weakness, eg, age of achievement of certain
      motor milestones or loss of functions. For the ambulatory status, we define
      "being ambulatory" as having the ability to walk for 100 meters, either with
      assistance such as calipers or walkers or without assistance. Actuarial survival
      curves were obtained by using the Kaplan-Meier method for calculating survival
      probabilities and probabilities of remaining ambulatory. The parents or the chief
      caregivers were interviewed for functional status using WeeFIM at the last
      registered date in September 2002. The WeeFIM consists of 3 domains: 1) self
      care, 2) mobility, and 3) cognition. The self-care domain consists of 8 items,
      namely eating, grooming, bathing, dressing (upper body), dressing (lower body),
      toileting, and bladder and bowel management. The mobility domain consists of 5
      items: transfer from chair or wheelchair, transfer to toilet, transfer to tub or
      shower, walking/wheelchair/crawling distance, and moving up and down stairs. The
      cognition domain assesses comprehension, expression, social interaction, problem
      solving, and memory. A scoring scale from 1 to 7 was used (1 = total assistance,
      2 = maximal assistance, 3 = moderate assistance, 4 = minimal contact assistance,
      5 = supervision, 6 = modified independence, and 7 = complete independence). The
      maximum total WeeFIM score is 126, and the maximum score for self-care, mobility,
      and cognition are 56, 35, and 35, respectively. RESULTS: For type I SMA (n = 22),
      the survival probabilities at 1, 2, 4, 10, and 20 years were 50%, 40%, 30%, 30%,
      and 30%, respectively. For type II SMA (n = 26), the survival probabilities at 1,
      2, 4, 10, and 20 years were 100%, 100%, 100%, 92%, and 92%, respectively. Sixteen
      of the SMA I patients and 4 of the SMA II patients died of cardiorespiratory
      failure. The 5 surviving SMA I patients all were ventilator dependent. All SMA
      III patients were surviving at the time of study. The probability of remaining
      ambulatory at 2, 4, 10, and 20 years after onset was 100%, 100%, 81%, and 50% for
      type IIIa (age of onset <3 years) and 100%, 100%, 84%, and 68% for type IIIb (age
      of onset between 3 and 30 years), respectively. The interval between disease
      onset and inability to walk was 15.0 +/- 10.9 years (mean +/- standard deviation)
      and 21.2 +/- 11.7 years for patients with SMA IIIa and IIIb, respectively. Only
      39 patients participated in the WeeFIM interview as 20 had already died at the
      time of study and 24 refused participation. No difference could be found in the
      age of onset, gender, or types of SMA between those who participated (n = 39) and
      those who did not (n = 24). The mean total WeeFIM quotients were 24% for SMA type
      1, 57% for SMA type 11, 75% for SMA type IIIa, and 78% for SMA type IIIb. For the
      self-care domain, 100% SMA type I and 73% SMA type II patients required
      assistance, whereas 55% and 63% of SMA types IIIa and IIIb patients achieved
      functional independence. Bathing and dressing (upper and lower body) were items
      with which most SMA children required help or supervision. For the mobility
      domain, assistance was needed in >90% of SMA types I, II, and IIIa and in 63% of
      SMA type IIIb patients. Stair management was the major obstacle for independence
      in achieving mobility for all types of SMA. For the cognition domain, performance
      was the best among the 3 domains, and 60% of SMA type II, 78% of SMA type IIIa,
      and 90% of SMA type IIIb patients achieved functional independence. However,
      except for SMA type IIIb, a significant proportion of patients still need
      assistance or supervision in the area of problem solving. Statistically
      significant differences were found in the WeeFIM scores between type I and type
      II and between type IIIa and IIIb patients. However, no significant difference
      could be observed between type II and type IIIa SMA patients in the overall
      WeeFIM scores or performance in any of the 3 domains. CONCLUSION: We found that
      there was improvement in survival in SMA patients as compared with other studies.
      Assistance or supervision was needed for the majority of SMA patients for both
      mobility and self-care domains. With improvement in survival as a result of
      medical advances, assessment of the most current or the best-ever functional
      status at a designated age might be an important criterion for classification of
      SMA.

PMID- 15492358
TI  - Association of breastfeeding with maternal control of infant feeding at age 1
      year.
AB  - OBJECTIVE: Previous studies have found that breastfeeding may protect infants
      against future overweight. One proposed mechanism is that breastfeeding, compared
      with bottle-feeding, may promote maternal feeding styles that are less
      controlling and more responsive to infant cues of hunger and satiety, thereby
      allowing infants greater self-regulation of energy intake. The objective of this
      study was to examine whether preponderance of breastfeeding in the first 6 months
      of life and breastfeeding duration are associated with less maternal restrictive
      behavior and less pressure to eat. METHODS: We studied 1160 mother-infant pairs
      in Project Viva, an ongoing prospective cohort study of pregnant mothers and
      their children. The main outcome measures were mothers' reports of restricting
      their children's food intake and of pressuring their children to eat more food,
      as measured by a modified Child Feeding Questionnaire (CFQ) at 1 year postpartum.
      Restriction was defined by strongly agreeing or agreeing with the following
      question from the modified CFQ: "I have to be careful not to feed my child too
      much." We derived a continuous pressure to eat score from 5 questions of the
      modified CFQ. We used multiple logistic regression to examine the association
      between preponderance of breastfeeding in the first 6 months of life,
      breastfeeding duration, and mothers' restriction of children's access to food. We
      used multiple linear regression, both before and after adjusting for several
      groups of confounders, to predict the effects of breastfeeding on the mothers'
      scores for pressuring their children to eat. RESULTS: The mean (SD) age of the
      women was 32.4 (4.8) years; 24% of the women were nonwhite, and 32% were
      primigravidas. At 6 months postpartum, 24% of the mothers were exclusively
      breastfeeding, 25% were mixed feeding, 41% had weaned, and 10% had fed their
      infants formula only. The mean (SD) duration of breastfeeding was 6.3 (4.5)
      months. Thirteen percent of the mothers strongly agreed or agreed with the
      restriction question. The mean (SD) score on the pressure to eat scale was 5.3
      (3.7), and the range was 0 to 20. After adjusting for mothers' preexisting
      concerns about their children's future eating and weight status, as well as
      sociodemographic, economic, and anthropometric predictors of breastfeeding
      duration, we found that the longer the mothers breastfed, the less likely they
      were to restrict their children's food intake at age 1 year. The adjusted odds
      ratio was 0.89 (95% confidence interval [CI]: 0.84-0.95) for each 1-month
      increment in breastfeeding duration. In addition, we found that compared with
      mothers who were exclusively formula feeding, mothers who were exclusively
      breastfeeding at 6 months of age had much lower odds of restricting their
      children's food intake at 1 year (odds ratio: 0.27; 95% CI: 0.10-0.72).
      Preponderance of breastfeeding in the first 6 months of life and breastfeeding
      duration (beta = -0.01 points on the 0-20 scale for each additional 1 month of
      breastfeeding [95% CI: -0.07 to 0.05]) were not related to mothers' pressuring
      their children to eat more. CONCLUSION: Mothers who fed their infants breast milk
      in early infancy and who breastfed for longer periods reported less restrictive
      behavior regarding child feeding at 1 year. Additional longitudinal studies
      should examine the extent to which any protective effect of breastfeeding on
      overweight is explained by decreased maternal feeding restriction.

PMID- 15492359
TI  - Hyperlactatemia in human immunodeficiency virus-uninfected infants who are
      exposed to antiretrovirals.
AB  - OBJECTIVE: Exposure to nucleoside analogues in fetal or early life has been
      associated with rare clinically significant mitochondrial toxic effects, mainly
      neurologic symptoms. Lactate (LA) measurements have been used to monitor
      nucleoside-related mitochondrial toxicity. Our aim was to determine the
      prevalence, clinical evolution, and risk factors for hyperlactatemia in our
      cohort of human immunodeficiency virus (HIV)-uninfected children who were exposed
      to antiretrovirals. METHODS: We conducted a prospective observational study of
      127 HIV-uninfected infants who were born to HIV-infected women. Clinical symptoms
      suggesting mitochondrial dysfunction were analyzed in routine follow-up, and LA
      and alanine plasma levels were obtained at 6 weeks, 3 months, 6 months, and 12
      months in all patients. Elevated alanine levels, together with hyperlactatemia,
      suggest chronic mitochondrial injury. RESULTS: Most (85%) women received highly
      active antiretroviral therapy (HAART) during pregnancy (mean duration: 31 weeks)
      and zidovudine during labor (93%). Most (96%) children received zidovudine alone.
      Hyperlactatemia with hyperalaninemia was detected in 63 children in at least 1 of
      the measurements. Mean LA levels were significantly higher in children who were
      exposed to nucleoside analogue reverse transcriptase inhibitors than in control
      subjects (2.88 vs 1.61 at 6 weeks, 2.78 vs 1.49 at 3 months, 1.89 vs 1.39 at 6
      months, and 1.71 vs 1.24 at 12 months; peak levels: 8.06, 10.1, 7.28, and 4.48
      mmol/L, respectively). In 44 patients, LA levels progressed spontaneously to
      normality within the first year of life. Three girls presented a slight and self
      limited delay in psychomotor development, with LA peak levels of 7.3, 4.0, and
      4.6 mmol/L. Only the gestational use of didanosine was associated with a higher
      risk of hyperlactatemia. CONCLUSIONS: In our series, almost half of the children
      (63 of 127) who were exposed to nucleoside analogues developed benign and self
      limited hyperlactatemia. When symptomatic, nucleoside analogue-induced toxicity
      affected neurologic development.

PMID- 15492360
TI  - Hand hygiene practices in a neonatal intensive care unit: a multimodal
      intervention and impact on nosocomial infection.
AB  - OBJECTIVE: Health care-associated infections persist as a major problem in most
      neonatal intensive care units. Hand hygiene has been singled out as the most
      important measure in preventing hospital-acquired infection. However, hand
      hygiene compliance among health care workers (HCWs) remains low. The objective of
      this study was to assess the frequency and nature of patient contacts in neonatal
      intensive care units and observe the compliance and technique of hand hygiene
      among HCWs before and after the implementation of a multimodal intervention
      program. METHODS: The nature and frequency of patient contacts, the hand hygiene
      compliance, and hand-washing techniques of HCWs were observed unobtrusively to
      reflect the baseline compliance and to investigate factors for noncompliance. The
      intervention consisted of problem-based and task-orientated hand hygiene
      education, enhancement of minimal handling protocol and clustering of nursing
      care, liberal provision of alcohol-based hand antiseptic, improvement in hand
      hygiene facilities, ongoing regular hand hygiene audit, and implementation of
      health care-associated infection surveillance. The observational study was
      repeated 6 months after the completion of the intervention program, which
      extended over 1-year period. RESULTS: Overall hand hygiene compliance increased
      from 40% to 53% before patient contact and 39% to 59% after patient contact. More
      marked improvement was observed for high-risk procedures (35%-60%). The average
      number of patient contacts also decreased from 2.8 to 1.8 per patient per hour.
      There was improvement in most aspects of hand-washing technique in the
      postintervention stage. The health care-associated infection rate decreased from
      11.3 to 6.2 per 1000 patient-days. CONCLUSION: A problem-based and task
      orientated education program can improve hand hygiene compliance. Enhancement of
      minimal handling and clustering of nursing procedures reduced the total patient
      contact episodes, which could help to overcome the major barrier of time
      constraints. A concurrent decrease in health care-associated infection rate and
      increase in hand hygiene compliance was observed in this study. The observational
      study could form part of an ongoing audit to provide regular feedback to HCWs to
      sustain the compliance.

PMID- 15492361
TI  - Establishment and maintenance of normal human keratinocyte cultures.

PMID- 15492362
TI  - Cultivation of normal human epidermal melanocytes in the absence of phorbol
      esters.

PMID- 15492363
TI  - Isolation and culture of human osteoblasts.

PMID- 15492364
TI  - Human osteoclast culture from peripheral blood monocytes: phenotypic
      characterization and quantitation of resorption.

PMID- 15492366
TI  - Human myoblasts and muscle-derived SP cells.

PMID- 15492365
TI  - Human chondrocyte cultures as models of cartilage-specific gene regulation.

PMID- 15492367
TI  - Cell cultures of autopsy-derived fibroblasts.

PMID- 15492368
TI  - Primary culture and differentiation of human adipocyte precursor cells.

PMID- 15492369
TI  - Human mononuclear phagocytes in tissue culture.

PMID- 15492370
TI  - Purification of peripheral blood natural killer cells.

PMID- 15492371
TI  - Human fetal brain cell culture.

PMID- 15492372
TI  - Culturing human Schwann cells.

PMID- 15492373
TI  - Well-differentiated human airway epithelial cell cultures.

PMID- 15492374
TI  - Isolation and culture of human alveolar epithelial cells.

PMID- 15492375
TI  - A new approach to primary culture of human gastric epithelium.

PMID- 15492376
TI  - Isolation and culture of human colon epithelial cells using a modified explant
      technique employing a noninjurious approach.

PMID- 15492377
TI  - Isolation and culture of human hepatocytes.

PMID- 15492378
TI  - Glomerular epithelial and mesangial cell culture and characterization.

PMID- 15492379
TI  - Isolation and culture of human renal cortical cells with characteristics of
      proximal tubules.

PMID- 15492380
TI  - Culture of parathyroid cells.

PMID- 15492381
TI  - Long-term culture and maintenance of human islets of Langerhans in memphis serum
      free media.

PMID- 15492382
TI  - Primary culture of human antral endocrine and epithelial cells.

PMID- 15492383
TI  - Conjunctiva organ and cell culture.

PMID- 15492384
TI  - Establishment, maintenance, and transfection of in vitro cultures of human
      retinal pigment epithelium.

PMID- 15492385
TI  - Gene targeting and transgenic strategies for the analysis of hematopoietic
      development in the mouse.
AB  - The generation of gene-targeted and transgenic mouse models facilitates the in
      vivo study of mammalian gene function. Advances in technologies to engineer the
      mouse genome have extended the choice of gene manipulation from straightforward
      gene inactivation or overexpression to detailed modification of gene expression
      pattern, structure, and function in desired cell types and at specific times.
      Combining conventional/conditional, knockout/knockin, inducible, and even
      reversible gene manipulation strategies provides the investigator with the
      freedom to design an optimal model to study the function of a gene in a specific
      organ system during development or in postnatal life. To maximize success,
      however, the requirements and limitations of each approach need to be considered.
      This chapter provides an overview of gene targeting strategies that are available
      for manipulation of the mouse genome. We emphasize approaches that aid the
      investigation of the development and function of the hematopoietic system in the
      mouse.

PMID- 15492386
TI  - Inducible transgene expression in mouse stem cells.
AB  - Embryonic stem (ES) cells serve as a potentially unlimited source of cells and
      tissues to treat a number of genetic and malignant diseases. The differentiation
      of these cells into specific cell types is an area of very active investigation.
      One method of manipulating ES cell differentiation is through the alteration of
      gene expression. There are a multitude of different methods for expressing a
      target gene in ES cells, but most are limited in their ability to provide
      spatial, temporal, and quantitative control of gene expression. These properties
      are important because many developmentally interesting genes are regulated in at
      least one of these ways. This chapter will address these limitations through the
      use of an ES cell line with a doxycycline-inducible transgene system. A
      characterization of this inducible transgene system will be discussed, as well as
      the use of this system to develop ES-derived long-term engrafting hematopoietic
      stem cells. This demonstration is one of many possible uses for this powerful and
      versatile system.

PMID- 15492387
TI  - Quantitative trait analysis in the investigation of function and aging of
      hematopoietic stem cells.
AB  - Extensive genetically determined quantitative variation exists in the number and
      function of hematopoietic stem cells in inbred mouse strains. Furthermore, aging
      of hematopoietic stem cells is genetically determined. Gene identification of
      quantitative trait loci involved in the regulation and aging of hematopoietic
      stem cells would provide novel insights into regulatory mechanisms that are
      relevant in vivo and may be clinically important. Here we describe strategies for
      mapping and gene identification of quantitative trait loci applied to traits
      contributing to the regulation of hematopoietic stem cells.

PMID- 15492388
TI  - Flow cytometric analysis of hematopoietic development.
AB  - More than 30 yr ago, a collection of cells isolated from the bone marrow were
      first demonstrated to repopulate hematopoiesis in a radioablated animal. These
      cells self- renewed while producing all of the blood products and were named
      hematopoietic stem cells (HSCs). Since then, HSCs have been a tremendous boon to
      both basic science in understanding cell biology and as therapy in a cancer
      transplant setting. More recent work has shown that the HSCs, and possibly
      populations of cells residing in other tissues, have the properties of stem cells
      and the ability to repopulate nonrelated organs and tissues. This promiscuous
      repopulation has been termed plasticity and is the center of much research and
      even more debate. Our laboratory has recently proven that the HSCs meet the
      requirements of a stem cell by self-renewing and producing all of the blood
      lineages while concurrently demonstrating their ability to produce
      nonhematopoietic endothelial cells of blood vessels. This plasticity of the HSCs
      demonstrates hemangioblast activity, proven by both single cell and serial HSC
      transplants, and is the focus of this chapter.

PMID- 15492389
TI  - Reconstitution of hematopoiesis following intrauterine transplantation of stem
      cells.
AB  - In utero hematopoietic stem cell transplantation is an entirely nonmyeloablative
      approach to achieve mixed hematopoietic chimerism and associated donor-specific
      tolerance. This chapter provides the rationale and methodologic detail for the
      administration of stem cells to the "preimmune" mouse fetus by a variety of
      routes. The development of murine model systems for in utero transplantation has
      accelerated progress in the field of in utero hematopoietic stem cell
      transplantation. Creative use of these models should also have experimental
      application to the fields of fetal gene therapy, stem cell biology, and
      developmental biology.

PMID- 15492390
TI  - Reconstitution of hematopoiesis following transplantation into neonatal mice.
AB  - The primary sites of hematopoiesis change during murine ontogeny. The first blood
      cells emerge in two waves in the yolk sac; primitive erythroblasts,
      megakaryocytes, and macrophages emerge on embryonic d (E) 7.0, whereas definitive
      progenitor cells appear as clusters within the yolk sac vasculature on E8.25. Of
      interest, yolk sac cells isolated prior to d 10.5 fail to engraft in myeloablated
      adult recipient mice and do not reconstitute hematopoiesis. We describe a method
      of sublethally myeloablating newborn mice in which E9.0 yolk sac cells engraft
      and repopulate all lineages of the hematopoietic system for up to 12 mo in
      primary recipients and up to 6 mo in secondary recipients. The exact mechanisms
      that permit yolk sac engraftment in the conditioned newborn mice remain elusive,
      but this method has been used by a number of investigators to pursue
      transplantation studies using embryo- or fetal-derived donor cells.

PMID- 15492391
TI  - Hemocyte development during Drosophila embryogenesis.
AB  - The model genetic organism Drosophila melanogaster has a rudimentary
      hematopoietic system with two embryonic blood cell types, crystal cells, and
      plasmatocytes. These distinct lineages provide the animal with an innate immune
      response and a means to remove apoptotic cells. Genetic analyses of Drosophila
      hematopoiesis have identified specific genes that function in blood cell
      formation. Complimentary deoxyribonucleic acid and antibody probes for these
      hematopoietic factors serve as important reagents to follow hemocyte lineage
      commitment and differentiation during embryogenesis. This is possible through
      methods described in this chapter on messenger ribonucleic acid localization by
      in situ hybridization and protein localization by immunohistochemical staining
      within hemocyte precursors and mature blood cells.

PMID- 15492392
TI  - Tracking and programming early hematopoietic cells in Xenopus embryos.
AB  - The fates of lineage labeled hematopoietic precursor populations in Xenopus
      embryos are followed by use of in situ hybridization, looking for overlap between
      lineage labeled cells and in situ probes specific for known cell populations or
      states of differentiation. By coinjection of dominant interfering constructs, it
      also is possible to define the environmental cues or signals required for
      specification and/or maintenance of the hematopoietic program at different times
      and locations in the early embryo. As a lineage trace, we use beta-galactosidase,
      which is injected as in vitro synthesized ribonucleic acid (RNA) in to Xenopus
      embryos at early cleavage stages. Because the interfering constructs we use also
      are in the form of injected RNA, the use of beta-galactosidase RNA as a lineage
      trace assures accurate determination of the cells expressing the dominant
      negative construct. Embryos are cultured to desired developmental stages, fixed
      briefly and processed for the beta-galactosidase reaction. Embryos are then
      analyzed by whole mount in situ hybridization, embedded in wax, and sectioned.
      Alternatively, after the beta-galactosidase reaction, embryos can be fixed long
      term in paraformaldehyde, mounted in wax, sectioned, and probed by in situ
      hybridization directly on sections.

PMID- 15492393
TI  - Fate mapping hematopoietic lineages in the Xenopus embryo.
AB  - Fate maps reveal the normal contribution of various regions of an early embryo to
      larval and adult structures. This chapter describes the mapping of primitive
      blood in embryos of the frog Xenopus laevis by the technique of lineage tracing
      with a fluorescent dextran.

PMID- 15492394
TI  - Analyses of immune responses to ontogeny-specific antigens using an inbred strain
      of Xenopus laevis (J strain).
AB  - In this chapter, the procedures for specific detection of ontogenic emerging
      antigens during animal development are described. Anuran metamorphosis has
      provided us with a good experimental model for investigation of the mechanisms of
      tissue remodeling. The establishment of a syngeneic strain of Xenopus laevis
      described in this chapter has enabled us to perform a unique experiment to
      develop antibodies that specifically react to ontogenic antigens by immunizing
      syngeneic animals. This strategy was successful because the antibody repertoires
      produced in the adult frog serum were well subtracted by a number of common
      antigens expressed in syngeneic larvae. Here we show, using results of
      immunohistochemical and T-cell proliferation analyses that adult frogs exhibit
      humoral and cell-mediated immune responses to larva- or metamorphosis-specific
      antigen molecules in epidermal cells.

PMID- 15492395
TI  - Use of flow cytometry and combined DNA surface staining for analysis of
      hematopoietic development in the Xenopus embryo.
AB  - Xenopus embryos provide a model for studying the earliest stages in the
      development of the vertebrate hematopoietic system. This chapter provides
      detailed procedures describing the production of hematopoietic chimeras in
      Xenopus embryos and the analysis of these chimeras using flow cytometry.
      Protocols for analysis include the determination of deoxyribonucleic acid content
      of hematopoietic cells, staining of cells with antibodies against cell surface
      antigens and the combined analysis of deoxyribonucleic content and cell surface
      phenotype. Examples of data that can be expected are included.

PMID- 15492396
TI  - Analysis of hematopoietic development in the zebrafish.
AB  - The zebrafish (Danio rerio) has emerged as a powerful vertebrate genetic and
      developmental model that is particularly amenable to the study of hematopoiesis.
      The zebrafish embryo develops externally and its optical clarity allows the
      number and morphology of circulating blood cells to be visualized using a
      dissecting microscope. Both the morphology of the blood lineages and the
      expression of critical blood genes are highly conserved between zebrafish and
      mammals. The high fecundity and short generation time of zebrafish facilitate
      genetic analysis, and a number of large-scale mutagenesis screens have identified
      mutations in genes affecting blood development. The discovery of novel
      hematopoietic genes, as well as the cloning of zebrafish homologs of known
      hematopoietic genes, necessitates the use of efficacious and reliable methods for
      complete gene characterization. In this chapter, we illustrate frequently used
      techniques that are essential for evaluating hematopoiesis in the zebrafish,
      including whole-mount in situ hybridization, the detection of erythrocytes by o
      dianisidine staining, and a description of the microinjection procedure, which
      has various applications, including overexpression of messenger ribonucleic acid,
      gene "knockdown" by antisense technology, and the creation of transgenic
      zebrafish. Also included is an explanation of the use of flow cytometry to
      separate hematopoietic lineages from the adult kidney and to isolate relatively
      pure populations of cell types from transgenic embryos based on the expression of
      fluorescent markers.

PMID- 15492397
TI  - Imaging early macrophage differentiation, migration, and behaviors in live
      zebrafish embryos.
AB  - Because zebrafish embryos are transparent, cell behaviors and interactions can be
      directly imaged noninvasively in live embryos using differential interference
      contrast-Nomarski light microscopy. We found that the imaging quality can be much
      improved by coupling differential interference contrast-Nomarski to true
      (analogical) color video so as to visualize the image in real time on a high
      resolution colour video monitor. We explain here how to apply this approach to
      the in vivo imaging of embryonic macrophages, which constitute a distinct early
      macrophage lineage, that originates from the rostral-most lateral mesoderm-
      adjacent to the cardiac field, differentiate in the yolk sac, and rapidly spread
      in embryonic tissues, although still retaining proliferative capacity.

PMID- 15492398
TI  - In vivo methods to analyze cell origins, migrations, homing, and interactions in
      the blood, vascular, and immune systems of the avian and mammalian embryo.
AB  - In vivo experimental approaches that have been designed to study the ontogeny of
      the hematopoietic system in higher vertebrates are described in the present
      chapter. The avian embryo is directly available to manipulations in ovo during
      gastrulation and organogenesis. This permissiveness has led to the design of
      various approaches that provided crucial insights into the ontogeny of the
      hematopoietic system, particularly regarding traffic of progenitors between
      different compartments. In contrast, experimental manipulation of the developing
      mouse in utero is possible only during the second half of gestation, that is, the
      fetal period. This approach has been very useful in understanding how the immune
      system learns to distinguish self from nonself.

PMID- 15492399
TI  - Mouse embryonic explant culture system for analysis of hematopoietic and vascular
      development.
AB  - In vertebrates, the earliest differentiated cell types (hematopoietic and
      endothelial) arise from mesoderm induced during the process of gastrulation.
      These cells become organized into the blood islands of the extraembryonic yolk
      sac and are morphologically apparent by around d 7.5 in the mouse. Additional
      waves of hematopoietic and vasculogenic/angiogenic activity later result in the
      development of definitive hematopoietic lineages and in the formation of the
      allantois and cardiovascular system of the embryo proper. In part because of the
      limited accessibility of the mammalian embryo to experimental manipulation in
      vivo, regulation of these events is still not well understood. Both in the yolk
      sac and within the embryo proper, prospective hematovascular mesoderm
      differentiates in the vicinity of endodermal tissues. Here we describe an
      embryonic explant culture system that permits the dissection of mesodermal and
      endodermal contributions to hematopoietic and endothelial cell formation during
      gastrulation. This system can be used to assay for soluble or endodermal cell
      associated molecules involved in mediating critical interactions between mesoderm
      and endoderm in the formation of the hematopoietic and endothelial lineages
      during embryonic development.

PMID- 15492400
TI  - Hematopoietic stem cell enrichment from the AGM region of the mouse embryo.
AB  - Hematopoietic stem cells (HSCs) constitute a pool of very rare cells able to self
      renew, proliferate, and/or differentiate to all the blood cell lineages during
      the life span. The first murine adult transplantable HSCs appear in the
      intraembryonic aorta-gonad-mesonephros region at embryonic day (E) 10.5. After
      E11, these HSCs are thought to seed the liver and then the bone marrow just
      before birth. So far, many questions concerning the origin, properties, and
      functionality of these HSCs have not been answered. To address these issues, it
      is necessary to isolate and purify them. One of the major problems concerning
      embryonic HSCs, as compared with their adult counterpart, is that they share many
      markers with endothelial cells at this early stage of development, making their
      purification very difficult. This review presents the best methods (sorting based
      on specific antibody staining, transgenic markers, cell cycle) for the
      purification and isolation of HSCs from the mouse embryo.

PMID- 15492401
TI  - Hematopoietic stem cell development during mouse embryogenesis.
AB  - The progress of the last few years in the understanding of hematopoietic cell
      development during embryogenesis resulted from a combination of experimental
      approaches used in hematology and developmental biology. This methodology has
      been particularly powerful for the analysis of the earliest steps of
      hematopoietic ontogeny because it allows for the first time the demonstration of
      the existence of two independent sites of hematopoietic cell generation. Here, we
      describe the methods used in our laboratories to characterize the phenotype and
      differentiation potential of the primordial hematopoietic precursors as well as
      their localization in the mouse embryo. This multidisciplinary approach is
      required to explore the mechanisms of hematopoietic cell generation.

PMID- 15492402
TI  - Analysis of hematopoietic progenitors in the mouse embryo.
AB  - All mature blood cells are derived from hematopoietic progenitors that have been
      defined by their ability to generate colonies of cells in semisolid media.
      Investigation of the cellular components of these colonies has confirmed the
      existence of unilineage, bilineage, and multilineage progenitors. Furthermore, it
      has led to a better understanding of the relationships that exist among the
      erythroid, myeloid, and megakaryocyte lineages that compose much of the
      hematopoietic hierarchy in the adult. More recently, the development of
      hematopoietic progenitors has been investigated in the mammalian embryo. The
      first progenitors arise in the yolk sac and subsequently expand in the fetal
      liver before settling into the postnatal bone marrow. This chapter describes the
      methodologies for the culture and identification of unipotential and
      multipotential hematopoietic progenitors in the mouse embryo.

PMID- 15492403
TI  - In vivo and in vitro assays of thymic organogenesis.
AB  - We describe two complementary methods for the study of early thymus organogenesis
      in the mouse. The first is an in vitro technique for lineage analysis, where a
      chosen population of cells within the mouse embryo is labeled with a fluorescent
      cell tracker dye. The embryos are then transferred to whole embryo culture for a
      defined period, after which time the location of the labeled cells is determined
      with respect to the developing thymus. In the second method, an in vivo assay is
      used to determine the ability of a specific tissue type to form a structurally
      and functionally normal thymus. This method uses an ectopic grafting technique
      where the embryonic pharyngeal endoderm containing the prospective thymus tissue
      is carefully isolated and transplanted under the kidney capsule of an adult
      mouse. Together, these techniques have allowed the cell types that make a
      physical contribution to the formation of the thymic epithelium to be identified.

PMID- 15492404
TI  - Retroviral transduction in fetal thymic organ culture.
AB  - T-cell development requires cytokines and intimate contact with stromal cells
      provided exclusively by the thymus. Consequently, an in vitro model of thymocyte
      differentiation, fetal thymic organ culture (FTOC), has been developed. FTOC
      recapitulates the normal development of T-cells derived from both mouse and human
      progenitor populations, providing a more rapid means to study T-cell development
      compared with alternative in vivo approaches. Furthermore, FTOC is easily
      amenable to genetic manipulation using retroviral gene transfer. In this chapter,
      we outline the basic FTOC technique and describe several applications, including
      retroviral transduction of mouse thymocyte subsets and human CD34+
      stem/progenitor cells.

PMID- 15492405
TI  - Expansion and differentiation of immature mouse and human hematopoietic
      progenitors.
AB  - A prerequisite for proper investigation of self-renewal and differentiation of
      hematopoietic cells is the possibility to obtain large quantities of homogenous
      primary progenitors under defined conditions, allowing meaningful biochemical and
      molecular analyses. These cells should show renewal and differentiation
      characteristics similar to the in vivo situation. The serum-free culture systems
      delineated in this chapter meet these requirements, employing primary
      hematopoietic cells derived from murine fetal liver and human umbilical cord
      blood, which show physiological self-renewal responses to cytokine/hormone
      combinations, which in vivo are involved in stress hematopoiesis. We describe the
      expansion and sustained proliferation of multipotent (mouse) and erythroid (mouse
      and human) progenitors, responding to physiological signals. Moreover, both mouse
      and human erythroid progenitors can be induced to undergo synchronous terminal
      differentiation by addition of high levels of erythropoietin. If fetal liver
      cells from p53-/- mice are used, respective multipotent and erythroid cells
      undergo immortalization without an obvious Hayflick crisis, but otherwise retain
      their primary cell characteristics. Finally, both primary and immortal mouse
      progenitors can be subjected to genetic manipulation via retroviral constructs
      with high efficiency.

PMID- 15492406
TI  - A new clonal assay system for lymphoid and myeloid lineages.
AB  - It has long been unclear how the pluripotent hematopoietic stem cell is
      restricted to the major lineage progenitors including the progenitors for
      myeloid, T- and B-cells. This is the result of the absence of a methodology
      capable of determining the developmental potential of individual progenitors to
      generate these major lineage cells. We have established such an assay system,
      termed the multilineage progenitor assay, as a modification of the fetal thymic
      organ culture system. By examining cells from murine fetal tissues with this
      assay, we have succeeded in elucidating the process of lineage restrictions in
      early hematopoiesis.

PMID- 15492407
TI  - Hematopoietic and endothelial development of mouse embryonic stem cells in
      culture.
AB  - Embryonic stem (ES) cells differentiate efficiently in vitro and give rise to
      many different somatic cell types. Hematopoietic progenitors present within
      differentiated ES cells (embryoid bodies, EBs) can be identified by replating EB
      cells into semisolid media with hematopoietic growth factors. The developmental
      kinetics of various hematopoietic lineage precursors within EBs and molecular and
      cellular studies of these cells have suggested that the sequence of events
      leading to the onset of hematopoiesis within EBs is similar to that found within
      the mouse embryo. Thus, the in vitro differentiation model of ES cells provides a
      unique opportunity to study onset mechanisms involved in hematopoietic
      development.

PMID- 15492408
TI  - Analysis of the vascular potential of hematopoietic stem cells.
AB  - The hematopoietic stem cells residing in the bone marrow have tremendous
      proliferative and self-renewing capacity, and until recently these cells were
      thought to produce only progeny of the blood lineages. We have recently
      demonstrated that these cells are capable of producing endothelial cells of blood
      vessels. This chapter will outline the methodology for producing chimeric mice
      through labeled bone marrow transplantation and induction of these donor cells in
      order to track their plasticity, or their ability to produce non-hematopoietic
      tissues, specifically blood vessels.

PMID- 15492409
TI  - Dynamic in vivo imaging of mammalian hematovascular development using whole
      embryo culture.
AB  - The yolk sac is the initial site of hematopoiesis in the mammalian embryo. As the
      embryo develops, blood vessels form around primitive erythroblasts to connect the
      yolk sac to the embryo, delivering newly formed blood cells to the embryonic
      circulation. The limited accessibility of the mammalian embryo has made it
      difficult to study the dynamic changes in cellular development during the
      formation of the early hematovascular system. Therefore, we have developed a
      culture system for studying early hematopoiesis, vasculogenesis. and angiogenesis
      in the mouse embryo. Early embryos (E7.5-E9.5) can be grown on the microscope
      stage to study the dynamics as vessels form and circulation begins. In addition,
      this mouse embryo culture system provides an excellent model for understanding
      the interplay between flow dynamics and cellular development.

PMID- 15492410
TI  - Fluorescent protein-cell labeling and its application in time-lapse analysis of
      hematopoietic differentiation.
AB  - Here, we present a computer-controlled time-lapse system for imaging of cultured
      hematopoietic cells labeled by the expression of different fluorescent proteins.
      First, we describe experiments to optimize the visualization of three green
      fluorescent protein variants (cyan-, green-, and yellow-enhanced fluorescent
      protein) and the red-fluorescent protein (DsRed) by standard wide-field
      fluorescence microscopy. Then, we describe procedures to best distinguish
      combinations of cells expressing these proteins using seven commercially
      available filter sets, based on the relative fluorescence intensities of the
      individual fluorescent proteins. Finally, we make recommendations about which of
      these filters to choose when working with specific fluorescent proteins.

PMID- 15492411
TI  - Analysis of hematopoietic development during human embryonic ontogenesis.
AB  - We describe here diverse methods used to study the onset of hematopoiesis in the
      human embryo and fetus. In the first part of this chapter, the criteria for
      estimating developmental stages in human embryos are discussed. This section also
      presents in detail a refined method for embedding and freezing intact human
      embryonic tissues that are destined to be analyzed by histology and
      immunostaining. In the second section, several protocols for the microdissection
      of human embryos are described in detail, with special attention given to
      differences encountered between tissues at different ages of gestation. Because
      of the limited number of cells available at the early stages of human gestation,
      we have established a miniaturized cell amplification system permitting further
      development of intact organ rudiments dissected from a human embryo and cultured
      in toto. The last part of the chapter is devoted to the study of myeloid and
      lymphoid potentials using, respectively, a mouse bone marrow-derived stromal cell
      line and cultured mouse embryonic thymus rudiments.

PMID- 15492412
TI  - Hematopoietic development of human embryonic stem cells in culture.
AB  - The isolation of embryonic stem (ES) cells from human preimplantation blastocytes
      creates an exciting new starting point to analyze the earliest stages of human
      blood development. This chapter describes two methods for the promotion of
      hematopoietic differentiation of human ES cells: stromal cell co-culture and
      embryoid body formation. Better understanding of basic human hematopoiesis
      through the study of human ES cells will likely have future therapeutic benefits.

PMID- 15492413
TI  - A functional genomics approach to hematopoietic stem cell regulation.
AB  - Elucidation of the molecular mechanisms that are responsible for regulating the
      most basic properties of stem cells, self-renewal, and differentiation remains a
      major challenge in hematopoietic stem cell biology. We have taken a functional
      genomics approach towards revealing these mechanisms. Previous studies of the
      fetal liver genetic program led to the development of Stem Cell Database (SCDb,
      http://stemcell.princeton.edu), a resource for the stem cell community. These
      studies have been expanded to include the microenvironmental component of
      hematopoiesis and are the focus herein. In our efforts to study the
      microenvironmental component we have identified a stromal cell line, AFT024,
      which serves as a surrogate stem cell niche. The line provides a milieu that
      facilitates the maintenance of transplantable mouse and human stem cells as well
      as the generation of large populations of committed progenitors. In a manner
      mirroring the work done with the SCDb, we provide an online resource, Stromal
      Cell Database, StroCDB (http://stromalcell.princeton.edu), that is a compendium
      of information and data derived from biological and molecular studies of this
      surrogate niche. These include bioinformatic analyses of over 6000 clones derived
      from a subtracted library enriched for messages expressed in AFT024 as well as
      data derived from custom expression arrays developed from this library. Herein we
      describe these efforts and provide a guide for navigating the database and mining
      the information contained within.

PMID- 15492414
TI  - Negative feedback regulation of phosphatidylinositol 3-kinase/Akt pathway by over
      expressed cyclooxygenase-2 in human epidermal cancer cells.
AB  - While enhanced expression of cyclooxygenase (COX)-2 has been observed in human
      skin epidermal cancer, the mechanisms underlying COX-2 expression have not been
      completely elucidated. Recently, a role for the phosphatidylinositol-3 (PI3)
      kinase pathway in COX-2 expression has attracted attention. We investigated COX-2
      expression, PI3 kinase activity, and the phosphorylation level of Akt, a
      downstream effector of PI3 kinase, in the human skin cancer cell line HSC-5.
      Compared to the nontumorigenic keratinocyte HaCaT, in HSC-5 cells, COX-2 protein
      expression and PI3 kinase activity were increased. The PI3 kinase inhibitor
      LY294002 reduced COX-2 expression in HSC-5 cells and, contrary to our
      expectation, the phosphorylation of Akt was significantly decreased. The
      expression of Bcl-2, which is regulated by Akt, was reduced, and apoptosis was
      induced in HSC-5 cells compared to HaCaT cells. COX-2 inhibitor NS398 up
      regulated Akt phosphorylation. These results imply that constitutively over
      expressed COX-2 down-regulates the Akt phosphorylation through a negative
      feedback mechanism.

PMID- 15492415
TI  - Intermittent topical corticosteroid/tacrolimus sequential therapy improves
      lichenification and chronic papules more efficiently than intermittent topical
      corticosteroid/emollient sequential therapy in patients with atopic dermatitis.
AB  - Atopic dermatitis (AD) is a common, chronic, relapsing, severely pruritic,
      eczematous skin disease. Topical steroids are the mainstay of treatment. However,
      the adverse effects of steroids on hormonal function are the major obstacle for
      their use as long-term topical therapy. Intermittent dosing with potent topical
      steroids and/or combination therapy with steroid and tacrolimus have been
      frequently used in the daily management of AD to overcome the problems
      accompanying the long term use of steroids. We compared the clinical effects of
      topical steroid/tacrolimus and steroid/emollient combination treatments in 17
      patients with AD. An intermittent topical betamethasone butyrate
      propionate/tacrolimus sequential therapy improved lichenification and chronic
      papules of patients with AD more efficiently than an intermittent topical
      betamethasone butyrate propionate/emollient sequential therapy after four weeks
      of treatment. Only one out of 17 patients complained of a mild, but temporary,
      burning sensation after tacrolimus application. The intermittent topical
      steroid/tacrolimus sequential therapy may be a useful adjunctive treatment for
      AD.

PMID- 15492416
TI  - Assessment of cadexomer iodine against Staphylococcus aureus biofilm in vivo and
      in vitro using confocal laser scanning microscopy.
AB  - Cadexomer iodine releases iodine (0.9% weight/weight) slowly from beads of
      dextrin and epichlorhydrin. This preparation is an effective debridement and
      antiseptic agent for chronic exdudative wounds. The purpose of the present study
      is to examine the influence of cadexomer iodine against glycocalyx production of
      Staphylococcus aureus isolated from furuncle lesions on cut wounds in mice using
      confocal laser scanning microscope (CLSM), and the increase in and glycocalyx
      production of S. aureus in vitro. In the present study, distinct S. aureus cells
      and glycocalyx were not detected in the dermis around the cadexomer iodine beads
      or within those beads, while S. aureus cells encircled by glycocalyx were soaked
      up by the cadexomer beads and were detected within them in vivo and in vitro. We
      suggest that cadexomer iodine soaks up S. aureus cells encircled by glycocalyx,
      directly destroys biofilm structures, and collapses glycocalyx during
      dehydration, and further, that iodine can subsequently kill S. aureus cells
      within biofilm. Cadexomer iodine is a promising treatment to clear S. aureus
      cells within biofilm from skin lesions of exudative or infectious wounds and to
      prevent wound exacerbation.

PMID- 15492417
TI  - Acrogeria with decreased gene expression of alpha1 (I) and alpha1 (III) collagen
      in cultured dermal fibroblasts.
AB  - We report a case of acrogeria. A 47-year-old Japanese man presented with
      micrognathism, thin lips, radial wrinkles around his month, atrophy of skin and
      subcutaneous tissue, and mottled hyperpigmentation on his extremities. A biopsy
      of the lesional skin showed flat epidermis and atrophy of the dermal layer. The
      in vitro life span of the patient's fibroblasts (18+/-2.2 PDL) was significantly
      shorter than that of control fibroblasts (42+/-3.5 PDL). The early-passage
      fibroblasts from the patient showed abnormal morphology which was also seen in
      the late-passage (in vitro aging) of normal fibroblasts. In northern blotting
      analysis of cultured dermal fibroblasts, mRNA levels of alpha1 (I) collagen and
      alpha1 (III) collagen were markedly reduced. These results revealed that patient
      fibroblasts might be in severe senescence in vitro and contribute to the
      phenotypes of this premature aging syndrome.

PMID- 15492418
TI  - Elevated serum antimelanocyte antibody level in cerebriform intradermal nevus
      with vitiligo.
AB  - We describe a rare, but typical case of cerebriform intradermal nevus associated
      with vitiligo. A 45-year-old man had a patch of alopecia over his vertex scalp
      for 15 years. The microscopic findings of the biopsy revealed a typical deep
      seated intradermal nevus and neuroid differentiation with a few pigments. Three
      hypopigmented patches developed on the forehead, cheek and index finger five
      years after the scalp lesion, with loss of both melanocytes and melanins. In
      addition, no dopa reactions were present. Compared to normal controls, the serum
      anti-melanocyte antibody level in the patient was elevated as determined by
      cellular enzyme-linked immunosorbent assay (cellular ELISA). This is the first
      reported case with elevation of serum antimelanocyte antibody level of
      cerebriform intradermal nevus with vitiligo. This antibody's presence may be
      related to the occurrence of the vitiligo in patient with cerebriform intradermal
      nevus.

PMID- 15492419
TI  - The lesional skin of linear IgA bullous dermatosis expresses growth-regulated
      peptide (GRO)-alpha.
AB  - The patient was a 62-year-old man with erythema with tense vesiculobullae and
      erosions on the bilateral elbows, right knee, and one buttock. A skin biopsy
      specimen revealed subepidermal blister formation with a predominant infiltration
      of neutrophils and papillary neutrophilic microabscesses. Direct
      immunofluorescence study showed linear deposition of IgA and weak deposition of
      IgG at the basement membrane zone of the lesional skin, and indirect
      immunofluorescence study showed linear deposition of IgA at the epidermal side of
      the 1M NaCl-separated normal skin. He was diagnosed with linear IgA bullous
      dermatosis. Immunohistochemical study revealed that the lesional and perilesional
      keratinocytes expressed growth-regulated peptide (GRO) -alpha, a potent
      chemoattractant for neutrophils. This suggests that GRO-alpha plays a role in the
      infiltration of neutrophils into the lesional skin and in bulla formation in
      linear IgA bullous dermatosis.

PMID- 15492420
TI  - Lupus panniculitis with combined features of dermatomyositis resulting in severe
      lipoatrophy.
AB  - An 11-year-old girl presented with a one-year history of multiple, hard, slightly
      painful subcutaneous nodules on her right cheek, upper arms, and buttock.
      Histology of a skin biopsy specimen showed a lobular panniculitis. Laboratory
      studies revealed positive ANA, anti-double strand DNA, and elevated muscle
      enzymes. She was diagnosed as having lupus panniculitis. During
      hydroxychloroquine treatment, erythema over knuckle joints developed. These
      unusual clinical and laboratory findings of panniculitis associated connective
      tissue diseases made it difficult to make a precise diagnosis. We report this
      unusual case of lupus panniculitis with combined features of dermatomyositis
      resulting in severe lipoatrophy.

PMID- 15492421
TI  - High-frequency ultrasound as a useful device in the preliminary differentiation
      of lichen sclerosus et atrophicus from morphea.
AB  - High-frequency ultrasound diagnostic equipment (HFUS) using probes with
      frequencies above 15-MHz has been utilized conventionally in preoperative
      assessments and postoperative follow-up of skin tumors. The advent of probes with
      even higher frequencies (up to 30-MHz) has widened the clinical applications of
      HFUS to inflammatory dermatoses which are histologically confined to the
      epidermis and upper dermis, such as psoriasis and atopic dermatitis. Ultrasound
      imaging has the advantage of being a noninvasive and relatively inexpensive
      technology that is quick and easy to perform. In addition, information obtained
      from HFUS is unique and useful for clinical diagnosis and evaluation for various
      skin disorders. We believe that HFUS has the potential to become a powerful tool
      for either clinical or investigative dermatology. Herein, we present a case of
      lichen sclerosus et atrophicus (LSA) to which we applied HFUS before skin biopsy
      and obtained substantial information for the differential diagnosis from morphea,
      and we reemphasize the usefulness of HFUS in studying the inflammatory skin
      disorders.

PMID- 15492422
TI  - A case of symmetrical leukemia cutis on the eyelids complicated by B-cell chronic
      lymphocytic lymphoma.
AB  - We describe herein a case of symmetrical bilateral leukemia cutis on the eyelids,
      especially on the lower lids, in a patient with B-cell chronic lymphocytic
      leukemia (CLL). The patient was a 63-year-old Japanese man who had been diagnosed
      with CLL. Eyelid swelling is well known to result from local skin or systemic
      diseases including tumors, hyperthyroidism, nephritic syndrome, and
      hypoalbuminemia. To our knowledge, symmetrical, bilateral, flesh-colored leukemia
      cutis on the eyelids has not been previously reported.

PMID- 15492423
TI  - Two cases of multiple eccrine spiradenoma with linear or localized formation.
AB  - We report two rare cases of recurrent, multiple eccrine spiradenoma. Both cases
      presented with extensive lesions comprised of multiple red papules of various
      sizes and a soft blue-red nodule. The first case was a 30-year-old woman. Her
      lesions followed a linear arrangement on her chin, and extended down the right
      side of the neck with spontaneous pain. The second case was a 57-year-old woman
      with tumors in a localized group on the left occipital region without pain. A
      search of the literature revealed only 15 reported cases of
      linear/zosteriform/nevoid multiple eccrine spiradenoma. Both cases were treated
      by surgical excision. Most of the red papules displayed typical histological
      features including two cell types: large clear cells with low-density cytoplasm;
      and small dark cells with high-density cytoplasm. The large soft tumors exhibited
      a variable histological appearance. In the first case, the cystic tumors
      displayed an homogeneous structure comprised of eosinophilic material. In the
      second case, the cystic tumors included abundant interstitial tissue.

PMID- 15492424
TI  - A case of Bowen's disease showing a clinical tendency toward spontaneous
      regression.
AB  - We present a case of Bowen's disease showing a clinical tendency toward
      spontaneous regression. The patient, a healthy 86-year-old woman, complained that
      erythema had appeared on her left forearm two years earlier and had gradually
      enlarged. At the first examination, we observed a well-demarcated, 4 x 3 cm,
      erythematous plaque, partically covered with crusting and erosions near the
      wrist. Diagnosis of Bowen's disease was confirmed by a biopsy. Since the patient
      refused surgery and also discontinued hyperthermic treatment with disposable
      chemical pocket warmers after a brief trial, we decided to continue the
      observation of disease progression without any treatment. Two years after the
      initial visit, the lesion showed a clinical tendency toward spontaneous
      regression, with a fine erythematous plaque that showed the obscurely demarcated
      border of the lesion. After three years, although the patient exhibited a similar
      symptomatic improvement, a skin biopsy showed a few residual tumor cells. At the
      patient's request, we chose to observe the progress of the lesion. We review the
      literature of cases of Bowen's disease that have shown a similar tendency toward
      spontaneous regression, which have been rare.

PMID- 15492425
TI  - A case of generalized hair follicle hamartoma associated with systemic lupus
      erythematosus.
AB  - A hair-follicle hamartoma (HFH) may be localized or diffuse. Generalized HFH is
      frequently associated with an autoimmune disease such as myasthenia gravis or
      systemic lupus erythematosus (SLE). We report here a female patient with SLE who
      developed typical generalized HFH. This is the fourth case of generalized HFH
      associated with SLE.

PMID- 15492426
TI  - Unusual erythemas with eosinophilia, caused by H2-blocker famotidine in a male
      patient with glioblastoma.

PMID- 15492427
TI  - Enterococcal bacteremia complicating pemphigus vulgaris: successful treatment
      with linezolid.

PMID- 15492428
TI  - Successful treatment of therapy-resistant plantar verrucae vulgares with systemic
      interferon-beta.

PMID- 15492429
TI  - Pancreatic carcinoma-associated subcutaneous fat necrosis improved by palliative
      surgery.

PMID- 15492430
TI  - Gardner-Diamond syndrome.

PMID- 15492431
TI  - Macrolactam immunomodulators (tacrolimus and pimecrolimus): new horizons in the
      topical treatment of inflammatory skin diseases.
AB  - Tacrolimus and pimecrolimus are new macrolactam immunomodulators which were
      developed for the treatment of inflammatory skin diseases, mainly atopic
      dermatitis. In this article, we review the pharmacologic properties of the drugs,
      their side effects, and their clinical uses.

PMID- 15492432
TI  - Skin aging and dry skin.
AB  - Skin aging appears to be the result of both scheduled and continuous "wear and
      tear" processes that damage cellular DNA and proteins. Two types of aging,
      chronological skin aging and photoaging, have distinct clinical and histological
      features. Chronological skin aging is a universal and inevitable process
      characterized primarily by physiologic alterations in skin function. In this
      case, keratinocytes are unable to properly terminally differentiate to form a
      functional stratum corneum, and the rate of formation of neutral lipids that
      contribute to the barrier function slows, causing dry, pale skin with fine
      wrinkles. In contrast, photoaging results from the UVR of sunlight and the damage
      thus becomes apparent in sun-exposed skin. Characteristics of this aging type are
      dry and sallow skin displaying fine wrinkles as well as deep furrows, resulting
      from the disorganization of epidermal and dermal components associated with
      elastosis and heliodermatitis. Understanding of the functions of the skin and the
      basic principles of moisturizer use and application is important for the
      prevention of skin aging. Successful treatment of dry skin with appropriate skin
      care products gives the impression of eternal youth.

PMID- 15492433
TI  - Efficiency of benzoyl peroxide-erythromycin gel in comparison with metronidazole
      gel in the treatment of acne rosacea.
AB  - Oral wide-spectrum antibiotics are the linchpin of rosacea treatment. Oral and
      topical metronidazole, topical tretinoin, and topical benzoyl peroxide may also
      be used in the treatment of rosacea. We aimed to show that benzoyl peroxide
      erythromycin gel is efficient in the treatment of acne rosacea. Fifty-six
      patients with acne rosacea were enrolled in our study. We administered benzoyl
      peroxide-erythromycin gel to 27 patients and metronidazole gel to 29 patients. In
      all the patients, the intensities of erythema, telangiectasia, papules/pustules,
      and nodules were evaluated before, during and after the treatment. The positivity
      of Demodex folliculorum from skin scratches was compared between the two groups
      at each visit. At the end of the therapy on the third examination, in the benzoyl
      peroxide-erythromycin group, 91.7% of the patients showed marked clinical
      improvement, and 8.3% of them showed complete remission. In the metronidazole
      group, 73.3% showed marked clinical improvement, and 26.7% of them showed
      complete remission. Clinical improvement in the papular component was 65.2% for
      the benzoyl peroxide-erythromycin group, and 81.5% for metronidazole group. In
      the first examination, the clinical results of the agents were similar. Although
      both of the drugs were found to be effective in the second and third
      examinations, metronidazole gel was more effective than benzoyl peroxide
      erythromycin. Both of the drugs were found to be significantly effective
      especially in treating the papular component of rosacea. Demodex folliculorum was
      found to be positive in 74.1% of the benzoyl peroxide-erythromycin group and in
      62.1% of the metronidazole group at the beginning. In the benzoyl peroxide
      erythromycin group, 40.7% of Demodex folliculorum positive patients, became
      negative by the first examination. This was 17.2% for the metronidazole group. In
      the benzoyl peroxide-erythromycin group, among the patients who were positive for
      Demodex folliculorum in the first examination, 37.5% of them became negative.
      This was 36.7% for the metronidazole group. Benzoyl peroxide-erythromycin gel was
      superior to metronidazole gel in decreasing Demodex folliculorum by the first
      examination, but the effect of the two drugs on Demodex folliculorum was similar
      by the second examination. As a result, topically applied combined benzoyl
      peroxide-erythromycin gel may be an alternative choice of treatment for acne
      rosacea.

PMID- 15492434
TI  - The clinical importance of demodex folliculorum presenting with nonspecific
      facial signs and symptoms.
AB  - Demodex folliculorum (D. folliculorum), found in the pilosebaceous unit, is the
      most common ectoparasite of humans. Various clinical forms such as pustular
      folliculitis, papulopustular scalp eruptions, perioral dermatitis, and
      blepharitis have been defined, although in general, the disease has been
      classified into three main groups as "pityriasis folliculitis", "rosacea-like
      demodicidosis", and granulomatous rosacea-like "demodicidosis gravis". Our aim
      was to test for the presence of D. folliculorum in pathogenic numbers in patients
      who came to our clinic with non-specific symptoms such as facial itching with or
      without erythema, seborrheic dermatitis-like or perioral dermatitis-like lesions,
      papulopustular lesions, and an acneiform clinical appearance without
      telengiectasia or flushing. Twenty-eight (87.5%) female and 4 male (12.5%),
      patients and 33 age-and-sex matched healthy subjects enrolled in this study. D.
      folliculorum was sought in the lesion sites using the non-invasive method known
      as the Standardised Skin Surface Biopsy (SSSB). The discovery of more than five
      parasites in an area of 1 cm2, was evaluated as pathogenic. For treatment, 5%
      permethrine cream was applied twice daily for 15 to 30 days. The clinical
      symptoms of the patients were classified into clinical groups and evaluated as
      facial itching in 2 (6.3%), nonspecific erythema and itching in 21 (65.6%),
      erythema and pityriasiform squamous lesions in 3 (9.4%), acneiform in 3 (9.4%),
      papulopustular lesions in 1 (3.1%), granulomatous rosacea-like in 1 (3.1%), and
      perioral dermatitis-like symptoms in 1 (3.3%), D. folliculorum density was
      determined as 5>D/cm2 in all clinical lesions. A significant clinical healing and
      density of D. folliculorum at <=5 D/cm2 was determined in all but two patients
      after treatment. We consider that D. folliculorum presentation with different
      symptoms and signs than classical forms is not rare. For this reason, we suggest
      that it is useful to test for D. folliculorum in patients with non-classical
      presentations like facial itching, itching accompanied by non-specific erythema,
      itching and non-specific pityriasiform squamous lesions, and acneiform lesions.

PMID- 15492435
TI  - Topical imiquimod 5% cream in external anogenital warts: a randomized, double
      blind, placebo-controlled study.
AB  - The complete treatment of anogenital warts has not been obtained with any
      combination of methods; therefore, new methods are still under investigation. In
      this study the activity and side effects of imiquimod 5% cream were investigated.
      The study group consisted of 23 male and 11 female volunteers and the control
      group of 9 male and 2 female volunteers. Patients applied the cream three times a
      week, every other day in the evenings for a period of 12 weeks. After the
      treatment, patients were regularly monitored for six months for recurrences. At
      the end of the study, 23 (69.7%) patients (all of females and 54.5% of males) in
      the study group displayed a complete clearance, 9 patients displayed 50-90%
      clearance and 1 patient displayed less than 50% clearance. In the control group,
      only 1 patient displayed a complete clearance, 1 patient displayed 50-90%
      clearance, and the other 8 patients showed no alteration in the lesions. These
      results were statistically significantly different (p<0.01). In 15 patients in
      the study group, no side effects were reported; the most frequently seen side
      effects were erythema and erosion. In six patients that were observed for a
      period of six months, recurrences occurred. Imiquimod 5% cream is a topically
      applied medicament that should be considered as an effective and reliable medical
      option in the treatment of anogenital warts.

PMID- 15492436
TI  - Clinico-histopathological correlation of skin and nerve in leprosy.
AB  - The histopathological features of skin tissue sections in patients clinically
      diagnosed as leprosy were correlated with the histopathological features of nerve
      specimens obtained from the same patients. Fifty untreated leprosy patients
      attending the Outpatient Department of the Department of Dermatology and Sexually
      Transmitted Diseases of Smt. Sucheta Kriplani and Kalawati Saran Children's
      Hospitals, New Delhi, India were included in the study. On correlating the
      histological features of skin and nerve tissue sections, concordant findings were
      found in 24 out of the 50 patients (48%) but discordance between the
      histopathological features of skin and nerve tissue sections were found in 26 out
      of 50 cases (52%). Of these 26 cases, the nerve tissue histology when compared
      with the skin histology showed features lower down the disease spectrum in 17
      (34%) cases. Seven of the 50 patients (14%) showed histological features of
      leprosy higher in the disease spectrum in the nerve tissue sections than in the
      skin biopsy sections. One patient clinically LL leprosy demonstrated
      histopathological features of Histoid leprosy in the skin sections and LL in the
      nerve sections. The remaining one patient had features of TT leprosy in the skin
      tissue sections while the nerve tissue histopathology showed non-specific
      changes. Histological features of the skin tissue sections were consistent with
      the clinical diagnosis in 33 out of 50 cases (66%). When the clinical groups were
      correlated with the histological features of the nerve tissue sections,
      concordance was found in 30 of the 50 cases (60%). On comparison of the
      histological features of skin and nerve tissue sections with the clinical
      diagnosis, concordance was still lower i.e., 19 out of 50 cases (38%). Thus the
      histological features of the skin tissue sections correlated more frequently with
      the clinical diagnosis than did those of the nerve sections. The importance of
      neural histology lies in the fact that it shows a higher BI and a lower
      histological grading in some cases and if not performed the lapse can result in
      inadequate treatment, drug resistance and even relapse.

PMID- 15492437
TI  - Cornification (keratinization) in Basal cell carcinoma: a histopathological and
      immunohistochemical study of 16 cases.
AB  - The concept of keratotic BCC is obscure and not well-defined. To elucidate the
      histopathological and immunohistochemical properties of cornification in BCC and
      to clarify the concept of keratotic BCC, by careful examination of 600 BCC
      specimens, we selected 16 cases of BCC that showed cornification. We investigated
      the precise histopathological features of these 16 cases, and studied the
      immunohistochemical expression patterns of anticytokeratin (CK) antibodies (CKs
      1, 10, 13, 14, 17) and other antibodies in these cornifying (keratotic) BCCs. We
      compared these data to those from normal adult hair follicles and three types of
      cornifying cysts (epidermal cyst, tricholemmal cyst and steatocystoma). Six types
      of cornification were observed in these BCCs; 1) infundibular type (4 cases) with
      thin laminated corneocytes expressing CKs 1 and 10, 2) tricholemmal (isthmus)
      type (9 cases) showing compact, homogenous cornified contents with CK 17
      expression on the surrounding cells, 3) inner root sheath type (1 case)
      characterized by compact, blue-gray corneocytes lined by CK 13 positive-squamous
      cells with red trichohyalin granules, 4) sebaceous duct type (1 case)
      characterized by crenulated cornified cells expressing CK 17, 5) apocrine
      acrosyringium type (2 cases) characterized by small duct-like structures lined by
      eosinophilic cuticle expressing CEA, in association with keratohyaline granules,
      and 6) cornifying microcyst type (10 cases) characterized by micro and small
      cystic structures containing the debris of cornified cells, which was associated
      with the infundibular or tricholemmal type and could be classified as having the
      primitive features of the tricholemmal type of cornification. The tricholemmal
      type could be subdivided into two groups: one with keratohyaline granules and the
      other without keratohyaline granules, and the cornified contents in approximately
      30% of the cornified areas in this type were positive for CK 17. The matrical
      type of cornification (seventh type) was not seen in our study. The examples
      described as "keratotic BCC" thus far were similar to BCCs with cornification of
      the tricholemmal (isthmus) or infundibular type. The cornification in BCCs could
      be classified into seven types. Excluding the cornifying microcyst type, the
      tricholemmal type is the most common type of cornification. This type will be
      abnormal and incomplete in attempts to cornify in the form of an isthmus,
      occasionally with concomitant exhibition of lower infundibular differentiation.
      The keratotic BCC is considered to be BCC with cornification of the tricholemmal
      (isthmus) or infundibular type.

PMID- 15492438
TI  - A case of refractory bullous pemphigoid with plasmapheresis-associated
      thrombopenia: efficacy of pulsed intravenous cyclophosphamide therapy.
AB  - We present a 69-year-old woman with refractory bullous pemphigoid successfully
      treated with pulsed intravenous cyclophosphamide therapy. Because various other
      early treatments including 4,4'-diaminodiphenylsulphone (DDS),
      minocycline/nicotinamide, cyclosporin, azathioprine, high-dose oral prednisolone,
      and methylprednisolone pulse therapy were either ineffective or intolerable, she
      was treated with double filtration plasmapheresis, but she responded poorly with
      the rare complication of severe transient thrombopenia. Finally, she gradually
      recovered with pulsed intravenous cyclophosphamide therapy.

PMID- 15492439
TI  - Microscopic polyangiitis presenting urticarial erythema and Henoch-Schonlein
      purpura: two case reports.
AB  - Microscopic polyangiitis (MPA) is well known as a life-threatening member of a
      group of systemic vasculitis diseases. We report two cases of MPA. Case 1 was a
      79-year-old-man who had been diagnosed with anti-neutrophil-cytoplasmic-antibody
      associated vasculitis (ANCA associated vasculitis) with alveolar hemorrhage and
      crescentric glomerulonephritis (CrGN). He presented with urticarial erythema in
      the abdomen, legs and back. The skin biopsy specimens showed leukocytoclastic
      vasculitis on the upper dermis. Case 2 was a 74-year-old-man, who presented with
      purpura on the abdomen, buttocks and legs that were similar to Henoch-Schonlein
      purpura (HSP). He also suffered from interstinal pneumonia. His renal biopsy
      specimens showed glomerulosclerosis and the peripheral pattern anti-neutrophil
      cytoplasmic antibody (P-ANCA) was positive. We reviewed the skin eruptions that
      had been reported with MPA, including our cases.

PMID- 15492440
TI  - Urticarial erythema associated with IgA myeloma.
AB  - We report a case of atypical urticaria associated with IgA multiple myeloma. A 79
      year-old man presented with a two-month history of wheal-like erythema, which
      lasted approximately one week without any response to anti-histamines.
      Histological examination of a lesion revealed leukocytoclasia as well as
      perivascular leukocytic infiltration, being consistent with urticarial erythema.
      Laboratory investigation showed markedly elevated serum IgA concentration and M
      protein in serum protein electrophoresis. A bone marrow examination led to a
      diagnosis of myeloma. An immunofluorescence study failed to detect any IgA
      deposit in the lesion. However, the wheal-like eruptions disappeared when the IgA
      myeloma was treated and reappeared when it relapsed. We conclude that this long
      lasting urticaria was the cutaneous manifestation of IgA myeloma.

PMID- 15492441
TI  - Benign cutaneous Degos' disease: a case report and review of the literature.
AB  - We report a case of benign form of Degos' disease, a rare condition often
      characterized by multisystemic vasculopathy, and discuss the case by the light of
      the limited literature available. A 34-year-old male patient was admitted to our
      clinic with lesions on his neck and back and a history of not getting any benefit
      from previous acne medications. Dermatological examination revealed erythematous
      papules with hemorrhagic crusts on their surfaces and many well-defined atrophic
      scar tissues. Histopathological evaluation of a biopsy obtained from a lesion
      revealed the findings of Degos' disease. Further evaluation did not reveal any
      sign of systemic involvement. He was diagnosed with the benign form of Degos'
      disease.

PMID- 15492442
TI  - Cutaneous ulcerations following subcutaneous interferon beta injection to a
      patient with multiple sclerosis.
AB  - We report a case treated with interferon beta-1b for multiple sclerosis (MS), who
      developed severe cutaneous ulcers after six months of therapy. Interferon beta-1b
      had been used in a regimen of 8 million IU administered subcutaneously through
      oblique direction of the needle, twice a week. The cutaneous ulcers developed at
      inoculation sites, as a result of penetration of interferon beta into dermis.
      Other underlying diseases of coagulative or bleeding disorders or secondary
      infection were excluded. Histological features of non-specific inflammatory
      reactions including hyperplastic changes of blood vessels without any evidence of
      vasculitis were the prominent features in this case. Corticosteroid and
      interferon beta-1b therapy was continued on restricted sites on the extremities
      with care not to repeat injections at the same sites previously used. The
      administration of interferon beta into subcutaneous fatty tissues vertically
      reduced the incidence of dermal penetration of drug and occurrence of ulcerations
      in this patient. We review other case reports of severe cutaneous reactions
      associated with interferon beta-1b therapy in MS patients and conclude that local
      cytokine-mediated, adverse, immune reaction or non-specific cutaneous
      inflammatory reaction to interferon beta-1b initiated the skin ulceration long
      after institution of therapy at the injection sites, and the reaction might be
      related to the depth of injection.

PMID- 15492443
TI  - Lack of response to isotretinoin in annular elastolytic giant cell granuloma.
AB  - Annular elastolytic giant cell granuloma is a rare disease characterized by
      annular configurated lesions with typical histopathologic findings. We report a
      case of annular elastolytic giant cell granuloma in a 50-year-old male patient.
      Treatment modalities for this disease are limited and mostly unsatisfactory,
      although isotretinoin was found to be effective in a single case. However,
      systemic isotretinoin treatment of 12 weeks' duration was of no benefit in the
      presented case.

PMID- 15492444
TI  - Treatment of confluent and reticulated papillomatosis with azithromycin.
AB  - Confluent and reticulated papillomatosis (CRP) is a relatively rare disorder of
      unknown origin, mostly affecting young female adults. We here present the case of
      a 21-year-old male patient with confluent and reticulated papillomatosis. Skin
      examination revealed brownish, verrucous, hyperkeratotic, 2 to 5 mm papules,
      which formed confluent patches and plaques with a reticulate network on the
      interscapular area. The patient was initially treated with ketoconazole cream for
      two weeks without improvement. The disease can be rather persistent and resistant
      to topical therapy. Our case showed a satisfactory response to treatment with
      azithromycin. Although this treatment is known to be effective in some cases, the
      action mechanism of azithromycin on CRP is not fully understood.

PMID- 15492445
TI  - Mucinous eccrine nevus.
AB  - A 46-year-old man with an erythematous, tender, swollen patch on the dorsum of
      his left fourth toe visited us. The biopsied tissue showed a proliferation of
      normally structured eccrine glands and ducts surrounded with abundant materials
      confirmed as mucin by toluidine blue stain. Mucinous eccrine nevus is an
      extremely rare entity, and only two cases have been reported in the literature.
      We describe a case of mucinous eccrine nevus which was late in onset and
      presented as a swollen patch.

PMID- 15492446
TI  - Severe extra-palmoplantar pustulation associated with palmoplantar pustulosis.

PMID- 15492447
TI  - Localized hypertrichosis in subsiding psoriatic plaques.

PMID- 15492448
TI  - Systemic plasmacytosis with aseptic bone necrosis and high fever.

PMID- 15492449
TI  - Ligation therapy for pyogenic granuloma.

PMID- 15492450
TI  - Moderating effects of psychological job strain on the relationship between
      working hours and health: an examination of white-collar workers employed by a
      Japanese manufacturing company.
AB  - The effects of working hours on health were examined taking psychological job
      strain into account. White-collar workers employed at the main office of a
      Japanese manufacturing company provided data for analysis done in 1997. The
      eligible subjects were 286 workers aged 20-39. Causal relationships between
      working hours, health, and psychological job strain were examined by covariance
      structure analyses. The main findings were as follows: Not only working hours but
      also sleeping hours and vacations affected the workers' effort to deal with work
      as a work-related hour factor. Decision authority and skill discretion of
      Karasek's psychological job strain items significantly constituted a discretion
      in the work factor, and this factor moderated the effects of the work-related
      hour factor on health. The effects of psychological job strain, especially
      discretion, must always be taken into account in examinations of working hours
      and health.

PMID- 15492451
TI  - Effects of shift work on autonomic and neuromotor functions in female nurses.
AB  - Thirty-seven nurses with shift work, working under a rotating three-shift system,
      and 37 nurses without shift work, having worked during the daytime for one or
      more years prior to this study, were examined to assess the effects of shift work
      on cardiac autonomic and neuromotor functions. Their ages ranged from 25 to 58
      yr. The electrocardiographic (ECG) R-R interval variability, %LF and %HF (i.e.,
      proportions of sympathetic and parasympathetic activities, respectively), and
      LF/HF ratio were computed by means of autoregressive spectral and component
      analyses. The %LF and LF/HF ratio were significantly larger in the nurses with
      shift work than in those without shift work, although there was no significant
      difference in the heart rate-corrected QT interval on ECG between them. And, hand
      ear coordination differed significantly between the nurses with shift work and
      those without. Despite the presence of potential selection bias, it is suggested
      that shift work in nurses may cause not only a long-term sympathodominant state
      but also some neuromotor impairment.

PMID- 15492452
TI  - Effects of prednisolone and complex of vitamin B1, B2, B6 and B12 on
      organophosphorus compound-induced delayed neurotoxicity.
AB  - Protective effects of prednisolone as a synthetic adrenal cortical hormone and
      complex of vitamin B(1), B(2), B(6) and B (12) on organophosphorus compound
      induced delayed neurotoxicity (OPIDN) caused by leptophos and tri-o-cresyl
      phosphate (TOCP) as organophosphates (OPs) were examined. Nine groups of hens
      (six for each) were used. Eight groups received intravenous injection of 30 mg/kg
      of leptophos or 40 mg/kg of TOCP (four groups in each). Among them, three groups
      which received leptophos were given (p.o.) predonisolone (2 mg/body), vitamin B
      complex (25 mg/body) or both 3 h after OPs injection and then every day for 15 d
      (one group for each); the same treatment was performed on three groups which
      received TOCP. The remaining one group served as controls. It was observed that
      delayed neuropathy induced by OPs could not be resisted completely by the
      treatment with prednisolone or vitamin B complex, but clinical signs of OPIDN and
      pathological changes in hens that received these two protective agents after OPs
      were less severe than those in hens that received only OPs. Of these groups, the
      improvement in clinical signs was best shown in hens that received the both two
      protective agents. In addition, improvement in clinical signs among the hens that
      did not deteriorate to paralysis was observed. In particular, those which
      developed mild ataxia recovered well. It is indicated that combining
      administration of prednisolone and vitamin B complex early before clinical signs
      are manifest is effective in alleviating neuropathy. It is also suggested that
      recovery or good prognosis will be expected, as long as progression of the
      clinical signs is prevented before paralysis develops in delayed neuropathy.

PMID- 15492453
TI  - Association between cigarette consumption and proteinuria in healthy Japanese men
      and women from an occupational population.
AB  - The association between cigarette consumption and prevalence of mild proteinuria
      (30-99 mg/dl of albumin) was analyzed in 11,569 male and 4,715 female workers
      aged 18-67 yr recruited from an occupational population. Proteinuria was found in
      274 (2.4%) of the total male workers and in 50 (1.1%) of the total females.
      Stepwise logistic regression analyses showed that sex, suspected diabetes
      mellitus, blood pressure (BP) and Brinkman Index (BI) levels (0, 1-199, 200-499,
      500-799, 800-) were significantly related to proteinuria, and that the odds ratio
      of each BI level for proteinuria was 1.11 (C.I.: 1.01-1.67). In the subjects aged
      50 yr or older, after excluding those suspected of having hypertension and/or
      diabetes mellitus, the odds ratio reached 1.37 (C.I.: 1.15-1.63), with the gender
      difference then no longer significant. The odds ratio for proteinuria was
      calculated as 5.44 (C.I.: 2.27-13.0) in male and female smokers having a BI of
      500 or above and normal-high BP (130-139/85-89 mmHg) in comparison with
      nonsmokers having normal BP (<130/85 mmHg). These results suggest that heavy
      cigarette consumption represented by a BI of 500 or above is a risk factor of
      proteinuria even in healthy Japanese workers, particularly in those aged 50 yr or
      older and having normal-high BP.

PMID- 15492454
TI  - Work-related factors associated with visiting a doctor for a medical diagnosis
      after a worksite screening for diabetes mellitus in Japanese male employees.
AB  - This paper aims to investigate the work-related factors that affect whether
      Japanese male employees will seek a medical diagnosis after being screened for
      diabetes mellitus. Participants in this study received a questionnaire two months
      after receiving the results of their physical checkup. The analysis focused on
      213 regular employees of small and medium-sized companies who were aged 35-64 and
      who had tested positive for diabetes in a screening. Only 42% of the subjects
      visited a doctor for medical diagnosis during an average follow-up period of 47.5
      d. Cox's proportional hazard regression was used to analyze the length of time
      between the employees' receipt of the results and their first visit to a doctor's
      office. The employees who could comfortably take a day off, compared to those who
      found it difficult to do so, were more likely to visit a doctor (hazard ratio
      (HR) 1.94; 95% confidence interval (CI) 0.85, 4.42; p for trend 0.05). In
      addition, employees with a high level of psychological job control, compared to
      those with low level of job control, were more likely to visit a doctor (HR 1.80;
      95%CI 0.94, 3.45; p for trend 0.08). Employees who worked the longest (61 h per
      week or more) were less likely to visit a doctor than those working from 41 to 60
      h weekly (HR 0.41; 95%CI 0.17, 0.98). The findings suggest that a flexible work
      schedule, autonomy at work, and no excessive working hours tend to improve the
      chance of visiting a doctor after screening for diabetes mellitus.

PMID- 15492455
TI  - The effect of lung burden on biopersistence and pulmonary effects in rats exposed
      to potassium octatitanate whiskers by inhalation.
AB  - The effect of lung burden on biopersistence and histopathological changes caused
      by potassium octatitanate whiskers (POW) which is one of the asbestos substitutes
      were investigated for 1-yr and 4-wk inhalation periods. In the 1-yr inhalation
      experiment, male Wistar rats were exposed to POW (TW) for 6 h/d, 5 d/wk under the
      same conditions as a previous study of POW (PT1, JFM fiber) which is made by
      different manufacturer. The exposure concentration was 1.9 +/- 0.7 mg/m(3) and
      the mass median aerodynamic diameter (MMAD) and geometric standard deviation
      (GSD) in the chamber were 1.6 microm and 2.9. Rats were sacrificed at 3 d and 1
      yr after the inhalation experiment and TW deposits in the lungs were determined
      by ICP-AES. Lung burden at 3 d and 1 yr after the inhalation was 2.39 +/- 0.50 mg
      and 1.37 +/- 0.96 mg, respectively, the deposition fraction was 8.1% and
      biological half time (BHT) was 15 months. Aggregated dust cells and mild fibrotic
      changes around these dust cells were observed in the exposed rat lung. These
      results were almost the same as those obtained in the previous 1-yr PT1 study. In
      the 4-wk inhalation experiment, to investigate the effect of lung burden on
      biopersistence and histopathological change, male Wistar rats were exposed to
      PT1. The exposure concentration was 102 +/- 21 mg/m(3), MMAD (GSD), the
      geometiric mean length and diameter (GSD) of the PT1 in the chamber were 1.6
      microm (3.0), 2.2 microm (1.8) and 0.33 microm (1.5), respectively. Rats were
      sacrificed at 3 d, 1 wk, and 1, 3, 6 and 12 months after the inhalation
      experiment. The lung burden of POW at 3 d after 4 wk inhalation was 1.49 +/- 0.19
      mg, which was close to the estimated amount of overload. The BHT of the total
      mass (4.1 months) was not prolonged, but aggregated dust cells were observed in
      the subpleural region and around the bronchioles and mild fibrotic changes were
      observed only around the dust cells at one year after the 4-wk inhalation. It is
      considered that the excessive exposure which impairs the function of alveolar
      macrophage mediated clearance may cause the aggregation of dust cells and
      fibrotic changes.

PMID- 15492456
TI  - Ethnic differences in disability risk between Dutch and Turkish scaffolders.
AB  - The number of native Dutch and Turkish workers receiving a permanent disability
      pension in the Netherlands is still rising. To assess ethnic differences in
      disability risk between Dutch and Turkish scaffolders, a retrospective study was
      conducted within a large scaffolding company. Medical files for the period 1981
      2000 were used to gather information on ethnicity, age at entering service, age
      at becoming disabled, years of employment, the year to receive a disability
      pension, the disability diagnosis, and the percentage rating of the disability
      pension. In the past 20 yr, 131 Turkish and 125 Dutch scaffolders have become
      disabled. Musculoskeletal disorders were the primary reason for the diagnosis. No
      differences in diagnoses were observed, except for a small difference in
      cardiovascular disease. Turkish scaffolders started their work at an older age,
      received the disability pension at an older age, and had a longer duration of
      employment. Turkish scaffolders faced disability 2.48 (95% confidence interval
      1.94-3.18) times more often than their Dutch colleagues, adjusted for age.
      Explanations for the differences in disability risk between Dutch and Turkish
      scaffolders are sought in the older age at start of employment, lower mobility in
      the labour market, and less access to medical and social care. In future,
      employers, general practitioners, occupational health physicians and social
      security workers, as stakeholders in reintegration, should sufficiently attune
      their activities concerning care and cure for Turkish construction workers on
      long-term sick leave or during reintegration into other work.

PMID- 15492457
TI  - Liver cancer risk in Japanese male dentists: a long-term retrospective cohort
      study.
AB  - It has been speculated that dentists are at high risk for occupational exposure
      to bloodborne viruses such as hepatitis B and hepatitis C viruses. To assess the
      risk of the development of liver cancer among Japanese male dentists, we
      conducted a retrospective cohort study on 3,314 dentists of the Osaka Dental
      Association who were members between 1964 and 1985, the year before HBV
      immunization became available. By linking to the Osaka Cancer Registry, we found
      that during the period of 1964-1997, 36 of the dentists were diagnosed with liver
      cancer over a mean follow-up of 23.6 yr. The observed number of liver cancer
      cases was compared with the expected number, which was calculated by multiplying
      the number of person-years at risk by the corresponding age- and calendar time
      specific incidence rate from the Osaka Cancer Registry data. The male dentists
      had a significantly lower risk of developing liver cancer than the general
      population of Osaka (O/E=0.71, 95% CI=0.50-0.98). On subcategorical analysis by
      birth year or duration of follow-up, there was no significantly increased risk of
      developing liver cancer among the dentists. Contrary to our expectation, our
      findings indicate that Japanese dentists were not at increased risk of developing
      liver cancer compared with the general population.

PMID- 15492458
TI  - Physiological effect of vibrations on tractor drivers under variable ploughing
      conditions.
AB  - The vibration conditions to which tractor operators are subjected are complex and
      varied with multi axis translation and rotational vibration inputs to different
      parts of the body. Working under such conditions may lead to human fatigue and
      other driving related hazards. The present research was carried out to study the
      operators under varying conditions of vibration while driving a tractor with and
      without farm equipment on different fields. Test runs were conducted in wet and
      dry fields to determine the levels of vibration generated at different engine
      speeds. On the basis of this study three levels of vibration namely 2.5, 3.5 and
      5.0 m/s(2) were selected. Five subjects, all males, with no experience in the
      field of tractor driving participated in the study. The data were analyzed on the
      basis of three factor repeated measure kind of experimental design. The results
      showed that the main effects of farm equipment and the vibration level were
      statistically significant but the effect of field type was found to be
      statistically non-significant. The results of the study call upon the ergonomists
      to design and develop a tractor where the driver may be relieved of vibration
      induced stresses. Front loading of farm equipment is recommended for improved
      visibility and better working posture.

PMID- 15492459
TI  - Effect of occupational exposure to rayon manufacturing chemicals on skin barrier
      to evaporative water loss.
AB  - To evaluate the effects of the occupational exposure to rayon manufacturing
      chemicals (RMC, containing predominantly carbon disulfide (CS(2)) and minor
      sulfuric acid) in a rayon factory on the basal transepidermal water loss (TEWL),
      barrier integrity (BI), and sequential increasing TEWL profiles. Six Thais and
      five Chinese workers in the spinning department of a rayon manufacturing plant
      and five healthy unexposed controls were recruited as the test subjects. An area
      of 4.5 x 5.5 cm on the mid-side of the volar forearm on the right hand was
      stripped by means of moderate pressure with commercially available adhesive tape
      by the same technician throughout the experiment. The skin was progressively
      stripped until glistening. TEWL was measured at every three and five tape strips
      on the right hand. The corresponding site on the left hand was measured parallel
      as the self-control. We found significant differences in basal TEWL and in BI
      between Chinese workers and Chinese controls, and between Thai workers and
      Chinese workers, respectively. Two-stage patterns of progressive TEWL profiles
      were found in such a chronic and repeated occupational exposure to RMC containing
      CS(2). The occupational exposure to RMC could result in the perturbation of the
      skin barrier function. Basal TEWL might be more sensitive to chronic skin
      irritant exposure. The TEWL profile achieved to the glistening stage might be
      necessary to avoid erroneous pattern estimation. Due to the lack of Thais control
      in this study, the racial difference in response to the RMC warrants further
      study.

PMID- 15492460
TI  - Environmental mycological study and respiratory disease investigation in tussah
      silk processing workers.
AB  - This study presents the results of an investigation of respiratory symptoms,
      pulmonary function and chest X-ray examinations, and analysis of antibodies to
      fungi of 197 tussah silk-processing workers and 40 control workers. An industrial
      hygiene survey and environmental mycological studies were also conducted. The
      dust concentrations in tussah silk processing workshops were less than 5.1
      mg/m(3) on average, with a maximum of 7.8 mg/m(3) below the national health limit
      of 10 mg/m(3). Most dusts in all tussah silk processing workshops contained less
      than 1.2% silica. Numbers of isolated fungi in tussah silk processing workshops
      [755-6,544 cfu/m(3) (colony forming unit/m(3)), were significantly higher than
      those in control environments (63-472 cfu/m(3)). The prevalences of respiratory
      symptoms in tussah silk processing workers were higher than those in control
      workers. The prevalences of respiratory symptoms in exposed male non-smoking
      workers were 44.4% with chronic cough, and 38.9% with chronic phlegm
      respectively, which were significantly higher than those (12.5%, 12.5%
      respectively) in male non-smoking control workers (p<0.05). The prevalences in
      exposed male smoking workers were 42.9% with dyspnea, and 38.1% with chest
      tightness respectively, which were significantly higher than those (16.7%, 8.3%
      respectively) in male smoking control workers (p<0.01). The prevalences of
      respiratory symptoms in exposed female workers were 25.3% with chronic cough,
      38.0% with chronic phlegm, 31.0% with dyspnea, and 29.1% with chest tightness
      respectively, which were significantly higher than those (10.0%, 10.0%, 10.0%,
      5.0% respectively) in female control workers (p<0.01). Fifteen exposed workers
      often suffered from fever. Five X-rays were abnormal and four cases had nodular
      or patchy shadows. The prevalences of pulmonary function abnormalities in the
      exposed female group were significantly higher than those in control groups
      (p<0.01). The OD(450 nm) values for antibodies to fungi in tussah silk processing
      workers were significantly higher than those of control workers (p<0.05). The
      positive rates of anti-fungal antibodies in tussah silk-processing workers were
      also significantly higher than those of control workers (p<0.01). The results
      suggested that fungi might be one of the main allergens in respiratory diseases
      in the tussah silk processing workers.

PMID- 15492461
TI  - Nitric oxide modulation of the spontaneous firing of rat medial vestibular
      nuclear neurons.
AB  - Modulation of the spontaneous activity of rat medial vestibular nuclear neurons
      by nitric oxide was investigated using the whole-cell patch-clamp technique. The
      spike frequency was increased by sodium nitroprusside (SNP), a nitric oxide
      liberating agent, and it was also increased by another nitric oxide liberating
      agent, sodium-nitroso-N-acetylpenicillamine. L-Arginine, the substrate of nitric
      oxide synthase, increased the firing of the neurons. The increased SNP-induced
      firing was inhibited by 1H-[1,2,4]oxadiazolo[4,3-a]quinozalin-1-one (ODQ), a
      specific inhibitor of guanylate cyclase. These results suggest that nitric oxide
      increases the neuronal excitability of the neurons by a cGMP-dependent mechanism.

PMID- 15492462
TI  - Cardiovascular effects of an L/N-type Ca2+ channel blocker cilnidipine assessed
      in the chronic atrioventricular conduction block dogs.
AB  - Cardiovascular effects of cilnidipine, a dual L/N-type Ca2+ channel blocker, were
      evaluated in the chronic atrioventricular block dogs, of which systemic blood
      pressure and plasma catecholamine levels significantly increased in the pre-drug
      control. Administration of antihypertensive doses of cilnidipine (1 and 3
      microg/kg, i.v.) significantly decreased the total peripheral vascular
      resistance, mean blood pressure, and atrial rate and increased the cardiac
      output. These results suggest that cilnidipine not only decreases the blood
      pressure, but also decreases the sinus automaticity in the in vivo hypertensive
      condition with increased adrenergic tones.

PMID- 15492463
TI  - Angiogenesis in vitro: vascular tube formation from the differentiation of neural
      stem cells.
AB  - Neural stem cells (NSCs) were isolated from the mouse cortex on embryonic day
      12.5 and cultured by neurosphere formation in serum-free medium in the presence
      of basic fibroblast growth factor (bFGF). When NSCs were inoculated in collagen
      gels with 10% fetal bovine serum (FBS) and bFGF and incubated for 10 days, vessel
      like tube structures consisting of PECAM-1- or VE-cadherin-immunoreactive cells
      were formed in the gels. Moreover, the formation of vascular tube-like structures
      with a massive investment of alpha-smooth muscle actin-immunoreactive or GFAP
      immunoreactive cells was occasionally observed, indicating angiogenesis identical
      to cerebral vascular development in vivo. To examine whether NSCs are capable of
      producing endothelial cells, differentiation was induced by the addition of 10%
      FBS after bFGF withdrawal. Most of the cells displayed a cobblestone-like
      morphology. Immunological analyses and RT-PCR indicated that NSCs expressed
      endothelial cell-specific marker proteins such as PECAM-1, VE-cadherin, and Flk
      1; and these expressions were maintained or up-regulated during differentiation.
      Similar tube structures were also observed when the differentiated cells were
      inoculated in collagen gels and incubated for 5 days. These results suggested
      that NSCs give rise to two types of vascular cells, endothelial cells and mural
      cells in vitro, which have the ability to form vascular tubes.

PMID- 15492464
TI  - Differential inotropic effects of endothelin-1, angiotensin II, and phenylephrine
      induced by crosstalk with cAMP-mediated signaling process in dog ventricular
      myocardium.
AB  - Endothelin-1 (ET-1), angiotensin II (Ang II), and phenylephrine, an alpha1
      adrenoceptor agonist, share the common signaling process, resulting in activation
      of Gq protein-coupled receptor (GqPCR) to activate the hydrolysis of
      phosphoinositide (PI). They do not elicit any inotropic effect in isolated dog
      ventricular muscle. In the presence of forskolin or IBMX (3-isobutyl-1
      methylxanthine), ET-1 produced a dual effect, that is, a positive inotropic
      effect (PIE) and/or a negative inotropic effect (NIE) depending on concentrations
      of forskolin or IBMX present simultaneously with ET-1. Phenylephrine produced a
      definite PIE and Ang II induced a small and transient PIE in the presence of
      forskolin or IBMX, but they did not elicit a NIE. Facilitation of Ca2+ influx via
      L-type Ca2+ channel may play a crucial role in the crosstalk because GqPCR
      agonists produced, likewise a PIE in the presence of Bay k 8644. GqPCR agonists
      failed to induce a PIE in the presence of dihydroouabain or elevated [Ca2+]o.
      These findings indicate that the accumulation of cAMP or activation of L-type
      Ca2+ channels markedly modulates the inotropic response to GqPCR agonists in a
      manner that leads to a PIE in dog ventricular myocardium. In addition, ET-1, but
      not Ang II or phenylephrine, activates the signal transduction process that
      results in a NIE.

PMID- 15492465
TI  - An S-nitrosylated hemoglobin derivative protects the rat hippocampus from
      ischemia-induced long-term potentiation impairment with a time window.
AB  - Evidence suggests that S-nitrosylation is a biological process involved in
      cerebral ischemia. The aim of the present study was to elucidate the effects of S
      nitrosylated (SNO) polyethylene glycol-conjugated (PEG) hemoglobin (Hb) developed
      as an artificial oxygen carrier, which can absorb free NO and translocate NO to a
      sulfhydryl (SH) moiety, on ischemic cerebral dysfunction. Long-term potentiation
      (LTP) in the perforant path-dentate gyrus synapses of the rat hippocampus was
      evaluated as functional outcome 4 days after transient incomplete cerebral
      ischemia (2-vessel occlusion: 2VO, 10 min). SNO-PEG-Hb (250 mg/kg, i.v.)
      administered on Day 0, 1, 2, or 4 (immediately, 24 h, 48 h, or 96 h after
      reperfusion, respectively) alleviated 2VO-induced LTP impairment with a
      therapeutic time window. The effect was significant when SNO-PEG-Hb was
      administered on Day 1 or 2. SNO-PEG-Hb altered NOS features observed in the
      vehicle-treated 2VO rat, upregulation of eNOS, nNOS, and iNOS expressions at mRNA
      and protein levels; SNO-PEG-Hb further upregulated eNOS and nNOS and
      downregulated iNOS expressions. These findings suggest that SNO-PEG-Hb might have
      protective effects on the rat hippocampus from ischemia/reperfusion-induced
      functional damages, thereby increasing the therapeutic potential as an artificial
      oxygen carrier for use in the area of oxygen therapy.

PMID- 15492466
TI  - RNA editing and short variant of serotonin 2C receptor mRNA in neuronally
      differentiated NG108-15 cells.
AB  - Two types of serotonin 2C subtype receptor mRNA, receptor-type and short variant,
      has been reported. The expression of the receptor-type mRNA could be detected as
      well as the short variant in NG108-15 cells by using a high temperature stable
      reverse transcriptase and the expression of the receptor-type mRNA was enhanced
      in drug-induced neuronal differentiated cells. The deleted sequence of the short
      variant include the RNA editing site by adenosine deaminase. Analysis of the
      sequence at the editing site revealed that the mRNA of undifferentiated cells was
      highly edited at sites A and B and that cytosine deaminase activity may also be
      involved in neuronal differentiation.

PMID- 15492467
TI  - Cytochrome c release from oridonin-treated apoptotic A375-S2 cells is dependent
      on p53 and extracellular signal-regulated kinase activation.
AB  - We have reported that oridonin isolated from Rabdosia rubescens induces apoptosis
      of human melanoma A375-S2 cells within 12 h. In this study, TUNEL assay and flow
      cytometric analysis also indicate that one of the causes of A375-S2 cell death
      induced by oridonin was apoptosis. The cell death was preceded by the release of
      cytochrome c from the mitochondria. Twelve hours after treatment with oridonin,
      the ratio of Bax/Bcl-xL protein expression was increased and release of
      cytochrome c was decreased by an extracellular signal-regulated kinase (ERK) MAPK
      inhibitor (PD98059) and a phosphoinositide 3-kinases (PI3-K) inhibitor
      (wortmannin). A mitochondrial permeability transition (MPT) inhibitor,
      decylubiquinone, suppressed the release of cytochrome c without affecting Bax
      expression. The activation of p53 by oridonin was also blocked by wortmannin. In
      addtion, PD98059 and wortmannin significantly decreased oridonin-induced DNA
      fragmentation, but the p38 MAPK inhibitor (SB203580) did not after DNA
      fragmentation. Oridonin induced A375-S2 cell apoptosis by activating parallel p53
      and ERK pathways, increasing the ratio of Bax/Bcl-xL protein expression, and
      promoting the release of cytochrome c into the cytosol, resulting in apoptotic
      cell death.

PMID- 15492468
TI  - Implication of peroxisome proliferator-activated receptor gamma and
      proinflammatory cytokines in gastric carcinogenesis: link to Helicobacter pylori
      infection.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand
      dependent transcription factor involved in various processes including the
      inflammation and carcinogenesis. The aim of the present study was 1) to examine
      the mRNA and protein expression of PPARgamma in gastric cancer (GC); 2) to
      evaluate the effect of PPARgamma ligand (ciglitazone) on the proliferation and
      apoptosis of GC cell line; and 3) to assess the levels of gastric tissue
      proinflammatory cytokines, IL-1beta and IL-8, and plasma gastrin in GC patients
      before and after Helicobacter pylori (H. pylori) eradication. The trial material
      included 30 H. pylori-negative controls and 30 sex- and age-matched GC patients
      without or with H. pylori before and after its eradication. Expression of tissue
      PPARgamma, tissue levels of IL-1beta and IL-8, and plasma concentration of
      gastrin were significantly higher in H. pylori-positive GC compared to controls,
      but H. pylori eradication significantly reduced these parameters. Kato III cells
      incubated with alive H. pylori upregulated PPARgamma expression and ciglitazone
      inhibited cell proliferation and induced apoptosis. PPARgamma, proinflammatory
      cytokines and plasma gastrin appear to be implicated in H. pylori-related gastric
      carcinogenesis and PPARgamma agonists may have potential in cancer therapy.

PMID- 15492469
TI  - Convergence and divergence, a concept for explaining drug actions.
AB  - For the teaching and/or learning about drug actions and for the discovery and
      development of new drugs, it is important to understand how drugs act on living
      bodies. So far, there has been no clear description on the general principle of
      drug action in pharmacology textbooks. We propose two principles to depict the
      action mechanism of drugs. The first is that most, if not all, drugs act on
      proteins at the molecular level, that is, enzymes, receptors, ion channels, and
      transporters. The second is that a drug may cause divergent or convergent
      responses, resulting in changes of a physiological or pathological function of
      the human body. The concept of divergence and convergence can be used to explain
      the complex individuality of drug actions.

PMID- 15492470
TI  - Assessment of coronary artery calcification in hemodialysis patients using multi
      detector spiral CT scan.
AB  - Cardiovascular disease in association with coronary artery calcification (CAC) is
      the leading cause of death in patients with end-stage renal disease (ESRD). The
      evaluation of CAC has been performed by electron beam CT scan. The purpose of the
      present study was to assess CAC using multi-detector spiral CT (MDCT) and to
      evaluate contributors to CAC in these patients. Fifty-three patients on chronic
      hemodialysis participated in this study. Their mean age was 61.0+/-9.6 years, and
      the mean duration of dialysis therapy was 6.7+/-5.4 years. We used an automatic
      device to measure arterial pulse wave velocity (PWV) as an index of arterial wall
      stiffness. The aortic calcification index (ACI) was quantified morphometrically
      by CT scan. The CAC score correlated positively with ACI score (r =0.863, p
      <0.0001). Linear regression analysis indicated that the CAC scores correlated
      positively with age (r =0.406, p =0.0023), C-reactive protein (r =0.38, p
      =0.0047) and PWV (r =0.303, p =0.0271). Stepwise regression analysis indicated
      that ACI (beta-coefficient=0.862, p <0.0001) and arterial PWV (beta
      coefficient=0.303, p <0.0001) were independently associated with CAC score. The
      mean CAC score of patients with cardiac events (2,568.5+/-2,575.1 mm3) was
      significantly higher than that (258.0+/-409.2 mm3) of patients without cardiac
      events. In conclusion, our results showed clearly that assessment of CAC score
      using MDCT may be predictive for detecting the presence of coronary artery
      disease. CAC is indirectly associated with increased arterial stiffness and the
      extent of aortic calcification in hemodialysis patients. We did not find a
      significant correlation between CAC score and parameters of mineral metabolism,
      including serum levels of calcium, phosphorus and parathyroid hormone. A
      longitudinal prospective study is required to assess the predictive value of this
      technique in determining cardiac events in large numbers of hemodialysis
      patients.

PMID- 15492471
TI  - The timing of the reflected wave in the ascending aortic pressure predicts
      restenosis after coronary stent placement.
AB  - It has been reported that the reflection waveform in the ascending aortic
      pressure is associated with systemic arterial stiffness. Stiffening of the aortic
      walls leads to a decrease in coronary perfusion and an increase in restenosis
      rate. The purpose of this study was to evaluate whether the reflection waveform
      in the ascending aortic pressure could be used to predict restenosis after
      percutaneous coronary stenting. One hundred and three patients who underwent
      percutaneous coronary stenting were enrolled in this study. We measured the
      inflection time and augmentation index (AIx) to determine the reflection waveform
      in the ascending aortic pressure at angioplasty. We then prospectively
      investigated the effect of inflection time and AIx in relation to the subsequent
      risk of restenosis after coronary stenting. After adjustments for age, gender,
      smoking habits, hypertension, type 2 diabetes, hypercholesterolemia, stent size,
      and heart rate, the odds ratio of restenosis in inflection time was 4.62 (95%
      confidence interval (CI), 1.39 to 15.4) for the lowest tertile of the inflection
      time level compared with the highest tertile level. As for AIx, the odds ratio of
      restenosis was 6.96 (95% CI, 1.93 to 25.1) for the highest tertile of the AIx
      level compared with the lowest tertile level. Inflection time and AIx are related
      to restenosis after percutaneous coronary stenting.

PMID- 15492472
TI  - Herpes simplex virus type 2 infection is a risk factor for hypertension.
AB  - Herpes simplex virus type 2 (HSV-2), which has been recognized as a potential
      cardiovascular pathogen and implicated in carotid atherosclerosis and coronary
      artery disease, is independently associated with the future risk of
      cardiovascular death. Investigations have demonstrated that hypertension may be
      related to inflammation, and inflammation is one of the symptoms of HSV-2
      infection. This cross-sectional study investigated the correlation between HSV-2
      infection and essential hypertension. One thousand two hundred and forty four
      inpatients (488 patients with essential hypertension and 756 normotensives) were
      investigated serologically for the specific immunoglobulin G (IgG) to HSV-2 by
      enzyme-linked immunosorbent assay. Patients diagnosed with pheochromocytoma,
      primary aldosteronism, aorto-arteritis or renal artery stenosis were excluded.
      The prevalence of HSV-2 IgG seropositivity was significantly higher in the
      hypertensive group than in the normotensive group (38.3% vs. 29.8%, p =0.002).
      After adjustment for confounding factors, an association of HSV-2 IgG
      seropositivity with essential hypertension was found on binary logistic
      regression analysis. The adjusted odds ratio of essential hypertension was 1.4
      (95% confidence intervals, 1.1 to 1.8; p =0.005) for HSV-2 infection; the
      adjusted covariates included age, male sex, smoking, body mass index,
      dyslipidemia, diabetes and coronary artery disease. The results of this study
      indicated that HSV-2 infection might be an independent risk factor for essential
      hypertension.

PMID- 15492473
TI  - Practical efficacy of telmisartan for decreasing morning home blood pressure and
      pulse wave velocity in patients with mild-to-moderate hypertension.
AB  - The current guideline-recommended blood pressure values are difficult to maintain
      in general practice, partly due to the lack of ideal anti-hypertensive agents.
      Since morning hypertension has a high correlation with cardiovascular events,
      expectations that telmisartan, a long-acting angiotensin-II type-1 receptor
      blocker (ARB), can improve cardiovascular mortality are high. In this study, the
      efficiency of telmisartan in reducing morning hypertension and pulse wave
      velocity (PWV) as a practical surrogate endpoint was investigated. Seventeen
      unsupervised and 7 untreated hypertensive patients were prescribed telmisartan 40
      mg/day for 3 months. Medication already prescribed upon enrollment in this study
      was continued, with the exception of ARBs (all of which turned out to be losartan
      50 mg/day), which were discontinued and replaced with telmisartan. Morning home
      blood pressure (MHBP), office blood pressure (OBP), and brachial-ankle PWV
      (baPWV) were investigated in a prospective fashion. A stratified analysis was
      performed regarding previous use (group L) or non-use (group N) of losartan. Over
      a 3-month period, telmisartan was found to significantly reduce both OBP (from
      153+/-13/85+/-9 to 141+/-17/80+/-7 mmHg (p <0.01)) and MHBP (from 153+/-23/93+/
      11 to 137+/-22/82+/-10 mmHg (p <0.001)). Surprisingly, 7 patients (70%) from
      group L achieved an OBP of less than 140/90 mmHg by simply changing their
      medication to telmisartan. Furthermore, baPWV fell significantly from 1,892+/-334
      cm/s to 1,672+/-324 cm/s (p <0.01), which was greater than the change in baPWV
      estimated by OBP reduction. Here it must be mentioned that there were no
      significant differences between group L and group N in the courses of blood
      pressures and baPWV. In conclusion, telmisartan 40 mg/day was found to be
      effective for reducing MHBP and arterial wall stiffness in patients with mild-to
      moderate hypertension, and thus may also be effective for improving
      cerebrocardiovascular mortality.

PMID- 15492474
TI  - Association between angiotensin II type 1 receptor gene polymorphism and
      essential hypertension: the Ohasama Study.
AB  - Gene targeting approaches have suggested that the angiotensin II type 1 receptor
      (AT1R) is involved in blood pressure (BP) regulation and modulation of the effect
      of angiotensin II. The A1166C polymorphism of the AT1 receptor gene (AT1R/A1166C)
      is associated with hypertension in Caucasians, but not in Japanese. The goal of
      this study, the Ohasama Study, was to examine the association between AT1R/A1166C
      and hypertension, especially home BP, in the Japanese general population. The
      Ohasama Study was a cohort study based on Japanese rural residents of Ohasama
      Town in the northern part of Japan. Subjects who gave informed consent to the
      study protocol and genetic analysis were recruited. Home BP was measured twice in
      the morning within 1 h of waking up and in the evening just before going to bed.
      The TaqMan polimerase chain reaction (PCR) method clearly determined AT1R/A1166C
      genotypes (n =1,207). The genotype distribution of AT1R/A1166C was as follows: AA
      84%; AC 15%; CC 1%. There was almost no difference in baseline characteristics
      among the AT1R genotypes (AA, AC, CC). In the subjects not receiving
      antihypertensive medication (n =817), both casual BP and home BP were not
      different among the AT1R genotypes after adjusting for confounding factors (age,
      sex, body mass index, current smoking habit and current alcohol consumption). The
      frequency of hypertension showed no difference among AT1R genotypes after
      adjusting for confounding factors, though the AC and CC genotypes were more
      frequent in hypertensives than in normotensives. Our data suggested that the
      AT1R/A1166C polymorphism is not a major genetic predisposing factor for
      hypertension in Japanese.

PMID- 15492475
TI  - Increased plasma 8-isoprostane levels in hypertensive subjects: the Tsurugaya
      Project.
AB  - To examine the relationship between 8-isoprostane and blood pressure, we measured
      plasma 8-isoprostane concentration and home blood pressure levels in an elderly
      Japanese population. Our study population comprised 569 subjects aged 70 years
      and over who were not receiving antihypertensive medication. On the basis of
      their blood pressure values, the participants were classified into three groups:
      normotensive (home blood pressure <135/85 mmHg), hypertensive (home blood
      pressure 135/85-160/90 mmHg), and severely hypertensive (home blood pressure > or
      =160/90 mmHg). The mean plasma 8-isoprostane level in the severely hypertensive
      group (21.1+/-5.2 pg/ml) was significantly higher than that in the normotensive
      (20.2+/-4.9 pg/ml) or hypertensive (19.7+/-5.1 pg/ml) group, and this result was
      unchanged when we adjusted for possible confounding factors such as age, sex, use
      of vitamin A, C or E supplements, smoking status, drinking status, body mass
      index, use of non-steroidal anti-inflammatory drugs, history of diabetes,
      hypercholesterolemia, home heart rate and serum creatinine level. Thus, the level
      of plasma 8-isoprostane appears to be elevated in older subjects with severe
      hypertension.

PMID- 15492476
TI  - Eccentric dosing of nitrates does not increase cardiac events in patients with
      healed myocardial infarction.
AB  - This study was performed to investigate the risk of cardiac events by eccentric
      or continuous dosing of nitrates in patients with healed myocardial infarction. A
      total of 573 patients with healed myocardial infarction were assigned to one of
      two groups: a nitrate-treatment (n =239) and a nontreatment (n =334) group. The
      nitrate-treatment group was further subdivided into a group receiving eccentric
      dosing of nitrates (n =153) and a group receiving continuous dosing of nitrates
      (n =86). The mean observation period was 11.2+/-8.2 months. The cardiac events
      investigated were nonfatal and fatal recurrent myocardial infarction, death from
      congestive heart failure, sudden death, worsening angina and rebound angina.
      Baseline characteristics were also compared among the three groups to determine
      any effects on outcome. Among the patients receiving eccentric or continuous
      dosing of nitrates, the rates of cardiac events were 12.7/1,000 person.year and
      67.4/1,000 person.year, respectively, whereas the rate was 19.7/1,000 person.year
      in the nontreated patients. The incidence of cardiac events was significantly
      greater in patients receiving continuous dosing of nitrates than in the
      nontreated patients (p <0.05). Continuous dosing of nitrates thus increases
      cardiac events, and while eccentric dosing of nitrates does not increase them, it
      is also not effective at preventing them in patients with healed myocardial
      infarction.

PMID- 15492477
TI  - Blunted reduction of pulse pressure during nighttime is associated with left
      ventricular hypertrophy in elderly hypertensive patients.
AB  - Increased pulse pressure (PP) is recognized as a risk factor for cardiovascular
      disease, especially in elderly patients. However, blood pressure (BP) is known to
      have a circadian variation. Therefore, this study asked whether or not PP has a
      circadian variation and, if so, whether a circadian variation of PP has clinical
      importance. Ambulatory BP monitoring (every 30 min for 48 h) was performed in 255
      patients with untreated essential hypertension (24 to 82 years old; mean: 52+/-12
      years). Left ventricular mass index (LVMI) was estimated from M-mode
      echocardiography. PP was decreased during nighttime (10+/-11% reduction from
      daytime PP). Multivariate linear regression analysis showed that, among four
      variables-the degree of nighttime PP reduction, daytime PP, 48-h systolic BP, and
      nondipper hypertension-the degree of nighttime PP reduction had the strongest
      (inverse) correlation with LVMI in a subgroup of elderly patients (> or =60 years
      old, n =67) (standardized regression coefficient=-0.32, p =0.02), whereas this
      association was not significant in the whole patient population unclassified by
      age. Furthermore, a blunted reduction of nighttime PP in combination with
      nondipper hypertension was an incremental risk for increase in LVMI in the
      elderly patients. In conclusion, PP is reduced during nighttime, but the degree
      of reduction varies among patients. The blunted reduction of nighttime PP is a
      risk for left ventricular hypertrophy, an established predictor of hypertension
      induced cardiovascular events, and it may thus play a role in cardiovascular
      complications, especially in elderly patients with nondipper hypertension.

PMID- 15492478
TI  - Event-related brain potentials in elderly dippers and nondippers with recently
      diagnosed hypertension.
AB  - Several studies have shown a relationship between blood pressure (BP) and
      cognitive function. Yet very few studies have addressed circadian BP patterns in
      this context, perhaps due to poor availability of suitable methods to detect
      slight changes in the cognitive state. Today, brain event-related potentials
      (ERPs) allow us to detect subclinical changes in cognitive function. We enrolled
      30 elderly patients with recently diagnosed hypertension (<2 years) that had
      never been treated: 18 dippers and 12 nondippers. Patients underwent 24-h
      ambulatory blood pressure monitoring (ABPM). Careful assessment of their
      cognitive state was carried out using the mini mental state examination (MMSE),
      and the recording of P300 and N2 ERPs. No significant differences between the two
      groups were found. MMSE scores in dippers and nondippers were similar (29.5+/
      0.71 vs. 29.3+/-1.07, respectively; p =0.611), as were P300 latency values
      (377.78+/-33.28 vs. 364.67+/-35.12 in the central (Cz) position, p =0.310;
      379.22+/-32.94 vs. 365.25+/-35.07 in the occipital (Pz) position, p =0.277) and
      N2 wave latency values (253.83+/-24.9 vs. 249.17+/-24.47 in the Cz position, p
      =0.617; 251.56+/-25.86 vs. 246.58+/-25.46 in the Pz position, p =0.608). These
      data show no association between the nondipping pattern and lower cognitive
      function in elderly subjects with recent hypertension.

PMID- 15492479
TI  - Effect of cerivastatin on endothelial dysfunction and aortic CD36 expression in
      diabetic hyperlipidemic rats.
AB  - A mutation of the CD36 gene that encodes a fatty acid transporter has been
      reported to play a role in insulin resistance in spontaneously hypertensive rat
      (SHR). Statins reduce circulating cholesterol and triglyceride concentrations.
      The objective of this study was to determine the role of CD36 and the
      significance of statin therapy in insulin-resistance syndromes. We determined the
      isometric relaxation induced by acetylcholine or lecithinized superoxide
      dismutase (SOD) in aortas obtained from Otsuka Long Evans Tokushima Fatty (OLETF)
      rats, a model of insulin resistance and dyslipidemia, and normal control (Long
      Evans Tokushima Otsuka; LETO) rats with or without cerivastatin treatment. We
      also determined the effect of cerivastatin on aortic expression of CD36 and
      PPARgamma. The CD36 genotype and microsatellite markers on chromosome 4 were also
      determined. The relaxation induced by acetylcholine and lecithinized SOD were
      attenuated in OLETF rats but restored by a low dose of cerivastatin without
      significant changes in serum cholesterol. These relaxations were also restored by
      a high dose of cerivastatin with significant reductions in serum cholesterol and
      triglyceride. Cerivastatin increased the aortic expression of CD36 and PPARgamma
      mRNA in both LETO and OLETF rats. However, the basal level of CD36 mRNA and the
      increase in CD36 mRNA in response to cerivastatin were significantly lower in
      OLETF rats than in LETO rats. Although the abnormal CD36 genotype reported in SHR
      was not found in OLETF rats, the microsatellite markers of D4Rat151 and D4Rat115
      differed between OLETF and LETO rats. In conclusion, insulin resistance in OLETF
      rats may be partially due to an altered expression of CD36. Increased aortic
      expression of CD36 in response to cerivastatin could explain the reduction in
      serum triglyceride concentrations with statin therapy and may have pronounced
      beneficial effects in insulin-resistance syndromes.

PMID- 15492480
TI  - Role of aberrant iron homeostasis in the upregulation of transforming growth
      factor-beta1 in the kidney of angiotensin II-induced hypertensive rats.
AB  - We have previously shown that abnormal iron metabolism might be one underlying
      mechanism of the renal damage observed in the angiotensin II-infused rat.
      Transforming growth factor-beta1 (TGF-beta1) is known to play a crucial role in
      the development of renal damage induced by activation of the renin-angiotensin
      aldosterone system. The purpose of the present study was to examine the effects
      of an iron chelator and a free radical scavenger on the angiotensin II-induced
      upregulation of TGF-beta1 in the kidney. Rats were given angiotensin II (0.7
      mg/kg/day) via osmotic minipumps for 7 days. The expressions of the mRNAs of TGF
      beta1 and collagen types I and IV were significantly increased in response to
      angiotensin II treatment. Histologic analysis showed that TGF-beta1 expression
      was upregulated mainly in tubular epithelial cells, and occasionally in
      glomerular and perivascular cells, some of which were identified as monocytes
      and/or macrophages. Although tubular cells that overexpressed TGF-beta1 did not
      contain iron particles, angiotensin II-induced TGF-beta1 upregulation was
      suppressed by the iron chelator and the free radical scavenger. The free radical
      scavenger also suppressed angiotensin II-induced upregulation of heme oxygenase
      1, an oxidative-stress sensitive gene. By contrast, administration of iron
      dextran to rats induced upregulation of TGF-beta1 mRNA. Collectively, these data
      suggest that the renal iron overload and presumed subsequent increase in
      oxidative stress play a role in angiotensin II-induced upregulation of the mRNAs
      of TGF-beta1 and collagen types I and IV in the kidney.

PMID- 15492481
TI  - Cardioprotective effects of vasopeptidase inhibition vs. angiotensin type 1
      receptor blockade in spontaneously hypertensive rats on a high salt diet.
AB  - The aim of our study was to compare the cardioprotective effects of vasopeptidase
      inhibition with those of angiotensin type 1 (AT1)-receptor blockade, a diuretic
      and the combination of AT1-receptor blockade and a diuretic in an experimental
      rat model of essential hypertension on a high salt diet. Spontaneously
      hypertensive rats (SHR) (n =73) were divided into 6 groups to receive the
      following diet and drug regimens for 8 weeks: 1) low salt controls (NaCl 0.5%);
      2) high salt controls (NaCl 6%); 3) omapatrilat (40 mg/kg/d) on a high salt diet;
      4) losartan (30 mg/kg/d) on a high salt diet; 5) hydrochlorothiazide (HCTZ; 10
      mg/kg/d) on a high salt diet; and 6) losartan+HCTZ (30+10 mg/kg/d) on a high salt
      diet. Blood pressure was measured by tail-cuff plethysmography. The histological
      score of myocardial damage, myocardial collagen volume fraction (CVF), connective
      tissue growth factor (CTGF) expression and cardiomyocyte apoptosis were
      determined. As an antihypertensive, omapatrilat showed greater efficacy than
      monotherapy with losartan or HCTZ, and was equally effective as the combination
      of losartan+HCTZ. Assessed by myocardial damage score, omapatrilat and losartan
      protected cardiac morphology better than HCTZ or the drug combination.
      Omapatrilat decreased CVF to a greater extent than the other therapies, whereas
      losartan was most effective in decreasing CTGF expression. All drug treatments,
      except HCTZ, decreased cardiomyocyte apoptosis. Our findings provide evidence
      that both vasopeptidase inhibition and AT1-receptor blockade exert
      cardioprotective properties beyond their blood pressure-lowering effects.
      Cardioprotection was associated with prevention of cardiomyocyte apoptosis and
      inhibition of extracellular matrix formation.

PMID- 15492482
TI  - Medical consultation for gastro-oesophageal reflux symptoms: reasons and
      associated factors.
AB  - OBJECTIVES: To evaluate the frequency of medical consultation for gastro
      oesophageal reflux symptoms (GORS) and to ascertain reasons for consultation and
      associated factors. METHODS: Telephone survey of 2,500 persons using a validated
      questionnaire. Data were analyzed using multiple logistic regression, in which
      the dependent variable was consultation for GORS and the independent variables
      were sociodemographic factors and the clinical characteristics of GORS. RESULTS:
      Of those reporting GORS, 28% had consulted their physician about them in the last
      year. Main reasons for seeking medical advice were GORS-induced concern in 48%,
      and intensity of GORS in 42.6%. Factors independently associated with medical
      consultation were: housewife (odds ratio (OR) 1.9; 95% CI 1.1-3.4) or retired
      status (OR 2.3; 95% CI 1.3-4.1), frequent GORS (OR 2.4; 95% CI 1.6-3.5), severe
      GORS (OR 2.4; 95% CI 1.4-4.2), nocturnal GORS (OR 1.6; 95% CI 1.1-2.3), and
      association of epigastric pain (OR 1.7; 95% CI 1.0-2.7) or nausea (OR 1.7; 95% CI
      1.1-2.8). CONCLUSION: The high frequency of medical consultation for GORS in
      Spain makes it an important healthcare problem. The fact that half the patients
      seek medical advice due to concern about the nature of GORS illustrates the
      benefits of explaining the nature, treatment and prognosis of GORS. The clinical
      relevance of GORS does not reside in its frequency alone, since severe or
      nocturnal symptoms, albeit occasional, are also associated with medical
      consultation.

PMID- 15492483
TI  - Detection of acute brainstem infarction by using DWI/MRI.
AB  - Even using diffusion-weighted images (DWI) detection of acute brainstem
      infarction (BI) is still a challenge. To evaluate the clinical efficacy of a DWI
      protocol with improved spatial resolution all images of 44 patients with
      clinically possible BI on admission (24 patients with definite BI and 20 patients
      with other etiologies) and first DWI within 24 h after symptom onset were blindly
      reanalyzed for visibility and detection of BI on the first DWI by reviewers with
      different expertise levels. Neuroradiologists identified definite BI in 21 out of
      24 patients (sensitivity 90%, specificity 100%); neurologists and junior house
      officers achieved similar results (sensitivity 86 and 83%, specificity 98 and
      97%). The use of DWI allows a definite diagnosis of BI, even if raters have
      limited experience.

PMID- 15492484
TI  - Whole-brain voxel-based correlation analysis between regional cerebral blood flow
      and intelligence quotient score in Parkinson's disease.
AB  - The correlation between regional cerebral blood flow (rCBF) and intelligence
      quotient (IQ) score was investigated in patients with Parkinson's disease (PD)
      without severe dementia. We analyzed the (9mTc-ethyl cysteinate dimer single
      photon emission computed tomography quantitative images and Revised Wechsler
      Adult Intelligence Scale scores of 44 PD patients using statistical parametric
      mapping. Verbal IQ positively correlated with rCBF in the right ventral striatum
      and the bilateral prefrontal cortex, performance IQ positively correlated with
      rCBF in the right operculum, insula and the left middle temporal gyrus, and full
      scale IQ positively correlated with rCBF in the right operculum, insula and the
      ventral striatum. The identified areas may be functionally related to mild to
      moderate cognitive impairment in patients with PD.

PMID- 15492485
TI  - Two brothers with non-classical 21-hydroxylase deficiency: to treat or not to
      treat?
AB  - Variations in phenotype in 21-hydroxylase deficiency (21OHD) have cautioned
      against initiating treatment in the absence of abnormal clinical features. We
      report 2 Caucasian brothers with compound heterozygous mutations of the CYP21
      gene and mild clinical and biochemical features of late-presenting 21OHD. The
      index case presented aged 8.5 years with mild genital virilization and bone age
      advanced by 5 years. Elevated basal and synacthen-stimulated 17
      hydroxyprogesterone (17OHP; 22.4 and 246 nmol/l) and androstenedione (10.9 and
      19.9 nmol/l) levels confirmed 21OHD. His younger brother was investigated at age
      7.3 years, and although examination showed normal pre-pubertal genitalia, basal
      and synacthen-stimulated 17OHP (32.4 and 281 nmol/l) and androstenedione (6.2 and
      9.0 nmol/l) were abnormal, and bone age was advanced by 1.5 years. Because of
      actual or incipient virilization, both patients were treated with glucocorticoid
      replacement 8-12 mg/m(2)/day. This decision is discussed in the context of
      published guidelines for the management of 21OHD.

PMID- 15492486
TI  - Benchmarking a test of temporal orientation with data from american and taiwanese
      persons with Alzheimer's disease and american normal elderly.
AB  - Orientation questions are readily incorporated into longitudinal population
      surveys, but their value as a screening tool for cognitive impairment is
      uncertain. We evaluated the screening value of four orientation-to-time items
      (TTO) from the Mini-Mental State Examination (MMSE) by determining their
      association with full-scale MMSE scores. Data collected under protocols with
      strict eligibility criteria in the US (64 normal elderly, 242 persons with
      probable Alzheimer's disease) and Taiwan (241 persons with probable Alzheimer's
      disease) were analyzed. The TTO and full-scale MMSE scores were significantly
      correlated (p < 0.05) in persons with a Clinical Dementia Rating (CDR) score of 0
      or 1; this was not significant in persons with a CDR of >1 (p > 0.05). Both TTO
      and MMSE were significantly associated with education in persons with 0-7 years
      of education; some MMSE items, but none of the TTO items, were associated with
      education in persons with more than 7 years of education. TTO may be a useful
      component of cognitive screening efforts.

PMID- 15492487
TI  - Differential regulation of 3-beta-hydroxysteroid dehydrogenase and vanilloid
      receptor TRPV1 mRNA in sensory neurons by capsaicin and NGF.
AB  - It was the aim of the present study to investigate by RT-PCR the regulation of
      the mRNA of the neurosteroid-synthesizing enzyme 3beta-hydroxysteroid
      dehydrogenase (3beta-HSD) and of the vanilloid receptor TRPV1 in dorsal root
      ganglia (DRGs) of rats during the process of capsaicin denervation of primary
      sensory neurons and the following regeneration. The expression of 3beta-HSD in
      DRG was increased 3 days after the capsaicin treatment, and it remained at that
      level during a 22 day observation period. The expression of TRPV1, a specific
      marker of capsaicin-sensitive small sensory neurons connected to C- and Adelta
      fibers, was markedly reduced 3 days after the capsaicin treatment. It slowly
      recovered during the 22 days observation period reaching almost control levels on
      day 22. When the capsaicin-treated rats received 5 intraplantar injections of
      nerve growth factor (NGF), the prototypical neurotrophin for capsaicin-sensitive
      neurons, on day 1, 2, 3, 5 and 6, both the 3beta-HSD and the TRPV1 mRNA had
      returned to control levels at the time point 8 days after capsaicin. The present
      results demonstrate that both 3beta-HSD and TRPV1 are markers for
      neurodegeneration and neuroregeneration in capsaicin-sensitive primary afferent
      neurons, and that NGF is an effective tool to induce recovery after peripheral
      nerve injury.

PMID- 15492488
TI  - [Future directions of anti-allergic drugs].

PMID- 15492489
TI  - [A preventive method of asthmatic death: regional medical (hospital-primary care
      physician) cooperation].

PMID- 15492490
TI  - [Survey of awareness and current state of latex allergy among all health care
      workers at a university hospital].
AB  - For the first time in Japan, a large-scale survey to investigate awareness of
      latex allergy was carried out, targeting all health care workers at Fujita Health
      University School of Medicine (total 1512 people). At first, we used
      questionnaires to collect information regarding the level of awareness of latex
      allergy as well as the incidence of clinical symptoms when using natural rubber
      products. The results of the survey revealed that approximately 85% of
      respondents were aware of latex allergy. Among all respondents, approximately 19%
      had actual experience with clinical symptoms. As a result of skin tests conducted
      on respondents who had acknowledged clinical symptoms, 44 people (total 3.3%)
      were diagnosed with latex allergy. In addition, the results revealed that people
      who were diagnosed with latex allergy tended to suffer atopic dermatitis and hand
      eczema. Furthermore, it became evident that health care workers whose work
      environment involved frequent exposure to natural rubber products showed a higher
      incidence of latex allergy. We demonstrated that a specific IgE assay was not
      sufficiently sensitive for diagnosing latex allergy. However, skin tests such as
      prick and use tests were confirmed to be effective diagnostic measures for latex
      allergy.

PMID- 15492491
TI  - [Effects of drug adherence on patient outcomes to early treatment for Japanese
      cedar pollinosis].
AB  - Drug adherence is one of the important aspects in caring for patients with
      allergic rhinitis. To improve clinical efficacy of early treatment for Japanese
      cedar pollinosis (JCP), we evaluated the effect of drug adherence on patients'
      outcomes. Patients were randomly selected from 16 ENT clinical sites in Osaka and
      Wakayama between February 24 and March 8, 2003 (peak pollen season). Efficacy was
      assessed using patients' ratings of nasal and ocular symptoms and overall
      assessment in their condition compared with previous season ones. Costs include
      direct costs of the drugs used for treatment to JCP from January to February.
      Five hundred one patients taking early treatment were enrolled. Compared to low
      adherence patients, those who reported higher level of adherence significantly
      improved overall health condition, and achieved better symptom relief of
      rhinorrhea and nasal congestion. In multiple logistic regression analysis, the
      following factors were independent risk factors for low adherence: student
      (p=0.002), using OTC medications (p=0.006), and short-duration of medication
      (p=0.001). Low costs were also risk factor for low adherence. We conclude that
      taking medications for JCP for 22-28 days is the best way to enhance patients'
      outcomes.

PMID- 15492492
TI  - [Self-care for pollinosis of cedar and cypress--from a questionnaire survey].
AB  - For patients with pollinosis, self-care is important as well as medical care. In
      this study, we investigated the real situation of patients with pollinosis-how
      they manage their symptoms. A questionnaire-based examination was conducted among
      488 patients who visited National Osaka-Minami hospital and Sano ENT clinic. The
      onset of pollen dispersion occurred 17th Feb. 34.6% of patients visited before
      the onset of pollen dispersion. 45.5% of them had a checkup for allergens. 84.8%
      of them utilized pollen information. 41.4% of them did self-care. The rate of
      patients who utilized pollen information and did self-care was higher in female
      compared with male. The rate of those who did self-care was significantly higher
      in the patients who visited before pollen dispersion, who had a checkup for
      allergens, who utilized pollen information, compared with the patients did not.
      It is necessary to show the information of self-care as well as pollen, and
      suggest the importance of self-care against pollen allergens.

PMID- 15492493
TI  - [Changes in food allergen sensitization rates of Japanese allergic children
      during the last 15 years].
AB  - In order to evaluate the changes in food allergen sensitization rates of allergic
      children, serum samples from 85 patients about 15 years ago (past group) and
      those from 90 current patients (present group) were randomly selected, and the
      specific IgE for six food allergens (wheat, peanuts, sesame, mackerel, ovomucoid,
      and kiwi) were measured with the CAP-RAST system. Sensitivity rates (class 2 or
      higher) for wheat and peanuts were significantly higher in the present than in
      the past group. Although there was no statistical difference in sensitivity rates
      (class 2 or higher) for kiwi between the groups, sensitivity rates (class 1 or
      higher) of the present group were significantly higher than those of the past
      group, indicating that the number of cases mildly sensitized to kiwi has been
      increasing. This trend was especially marked among children aged 6 or younger,
      and there was no statistical difference in sensitivity rates among those aged 7
      or older. For the management of food allergy, special attention should therefore
      be paid not only to an increase in the number of patients, but also to changes in
      the kinds of causative foods.

PMID- 15492494
TI  - [The national survey of immediate type of food allergy].
AB  - There are not so many epidemiological data for food allergy in Japan due to lack
      of relevant investigation. Therefore we are to study the reality of the
      immediately type of food allergy by utilizing IgE and CAP-RAST data investigated
      in 1998 and 1999 by the Research Group of Public Welfare Ministry of Labor. The
      survey was conducted in cooperation with 2689 domestic hospitals which have
      pediatrics and more than 100 beds. We focused on patients who had the symptoms of
      allergy within 60 minutes after the intake of any offending food. The
      questionnaire was returned by 498 hospitals (collect rate 60.4%), which reported
      1420 cases. We did not find clear relation between serum IgE and frequency of
      food allergy symptom and admission rate. On the other hand, we recognized that
      CAP-RAST had significant differences in the frequency of shock disease caused by
      the intake of milk products whereas there were no differences in any other major
      antigens. We concluded that both serum IgE value and CAP-RAST Class cannot
      indicate the severity of the immediate type of food allergy.

PMID- 15492495
TI  - [A case of hypersensitivity pneumonitis caused by Lyophyllum karst].
AB  - A 52-year-old woman who has worked at factory to check pack Lyophyllum karst for
      six years consulted another doctor for dry cough as common cold. After a month,
      low grade fever, dyspnea on effort, and productive cough brought her to our
      hospital. Her chest radiographs showed multiple small nodular shadows and ground
      glass opacities in entire lung fields. Histopathological examination of
      transbronchial lung biopsy specimen revealed granuloma and thickening of alveolar
      septa with lymphocytes infiltration. She was admitted to our hospital for
      hypersensitivity pneumonitis and prescribed predonisorone 30 mg/day. Her symptoms
      and the finding of chest radiograph improved in two weeks. The precipitation
      antibodies to Lyophyllum karst were positive and the symptoms exacerbated by
      going to work. Those finding suggests that hypersensitivity pneumonitis in this
      case. After quitting her job, she has had no relapse by tapering steroids.

PMID- 15492496
TI  - Translation of scientific insights to benefit patients with cancer.

PMID- 15492497
TI  - Chromatin dynamics and cancer.
AB  - Chomatin remodeling multi-protein complexes play a key regulatory role in many
      physiological processes such proliferation and differentiation. The alteration in
      the recruitment or in the function of one of these chromatin remodeling factors
      can lead to a proliferation defect, that might result from the aberrant
      activation or repression of key genes that regulate cell proliferation. In fact,
      aberrant chromatin remodeling leads to severe human diseases such as leukemia,
      epithelial cancers and Rubinstein-Taybi syndrome.

PMID- 15492498
TI  - Microsatellite instability and loss of heterozygosity have distinct prognostic
      value for testicular germ cell tumor recurrence.
AB  - Germ cell tumor (GCT) is the most common genitourinary malignancy of men between
      the ages of 18 and 35 years. Therapy is ultimately successful in over 90% of
      patients, however significant morbidity and mortality can be associated with
      adjuvant treatment and relapse. Molecular markers that predict treatment response
      and/or poor outcome would have immediate clinical benefit since adjuvant
      treatment could be selectively reserved for patients at higher risk for relapse
      and those patients most likely to respond to treatment. In order to identify
      potential prognostic molecular markers, we evaluated 118 GCT for microsatellite
      instability (MSI), loss of heterozygosity (LOH) and MSH2 immunostaining to
      identify tumors associated with relapse and/or poor outcome following initial
      surgical, medical and/or radiation therapy. MSI in 3 or more markers and/or low
      MSH2 staining were associated with relapse while LOH in the absence of MSI and/or
      high MSH2 staining were not. Twenty-five percent of GCT exhibited genetic
      instability in 3 or more microsatellite markers (MSI+ tumors), 15% exhibited LOH
      in the absence of MSI (LOH only tumors) and 44% exhibited decreased or absent
      MSH2 immunostaining (low MSH2 staining tumors). Thirty-six patients (30%)
      relapsed and 27 of these patients (75%) had MSI+ and/or low MSH2 staining tumors.
      Only one patient (3%) with an LOH only tumor and no patients with high MSH2
      staining and LOH only tumors relapsed. Therefore distinct GCT subpopulations
      identified by detection of MSI, LOH and MMR expression are associated with
      different clinical outcomes. MMR deficient testicular GCT with increased
      frequency of MSI had an increased association with tumor recurrence compared to
      GCT with an intact MMR system and LOH in the absence of MSI.

PMID- 15492499
TI  - Lessons learned pursuing translational research.

PMID- 15492500
TI  - Characterization of a specific phage-displayed Peptide binding to vasculature of
      human gastric cancer.
AB  - Antivascular therapy provides a promising method for anticancer therapy. But
      targeting to gastric cancer vessels is nonselective due in part to the lack of
      specific cell-surface receptors identified on target vascular cells. Herein we
      used in vivo screening of phage displayed peptide library to identify some
      peptides that bind selectively to endothelial cells of human gastric cancer
      rather than nonendothelial cells. After four rounds of selection, one phage was
      obtained with a cyclic 7-mer peptide CGNSNPKSC homing to human gastric
      adenocarcinoma . There was a 4.6 approximately 137.26-fold increase in the number
      of the selected phage in gastric cancer xenograft in comparision with control
      organs brain, heart, liver, spleen and kidney. Immunohistochemistry in mouse and
      human tissue showed that this phage peptide only bind to the endothelial cells of
      human gastric cancer. This peptide was observed only specific binding to HUVEC
      not to SGC-7901, Eca-109, LoVo and Hep-G2 by ELISA. The competitive and
      inhibitory result between the synthetic CGNSNPKSC peptide and the phage
      displaying the peptide CGNSNPKSC on HUVEC and in vivo was also confirmed its
      specific binding effect. This peptide may be a possible candidate for targeted
      drug delivery in antivascular therapy.

PMID- 15492501
TI  - Differential oncogenic Ras signaling and senescence in tumor cells.
AB  - Several studies have shown that forced expression of oncogenic H-ras can induce a
      senescence-like permanent growth arrest in normal cells. Here we report that
      expression of oncogenic H-ras in human osteosarcoma U2OS cells also resulted in a
      senescence-like flat and enlarged cell morphology and permanent growth arrest. In
      contrast to normal human fibroblasts, U2OS cells were arrested independently of
      the p16 and ARF tumor suppressors. Treatment with a MEK inhibitor or a p38MAPK
      inhibitor interrupted oncogenic H-ras-induced growth arrest in U2OS cells,
      suggesting that activation of MAPK pathways is important. To further determine
      whether this process is unique to oncogenic H-ras signaling, we examined the
      effect of oncogenic K-ras on normal cells and human osteosarcoma cells. Similar
      to oncogenic H-ras, oncogenic K-ras also induced senescence in normal
      fibroblasts, while transforming immortalized mouse fibroblasts. However, in
      contrast to oncogenic H-ras, oncogenic K-ras failed to induce a permanent growth
      arrest in osteosarcoma U2OS cells. Additionally, cells transduced with oncogenic
      K-ras exhibited distinguishable cellular changes compared to those transduced
      with oncogenic H-ras. In summary, we report for the first time that oncogenic H
      ras signaling can trigger a senescence-like growth arrest in tumor cells,
      independent of the p16 and ARF tumor suppressors. This result suggests that tumor
      cells may harbor a senescence-like program that can be activated by ras
      signaling. Moreover, our study uncovered a cell type-dependent differential
      response to oncogenic K-ras, as compared to oncogenic H-ras.

PMID- 15492502
TI  - Cytokine overexpression and constitutive NFkappaB in cancer.
AB  - The NFkappaB family of transcription factors, central mediators of immune
      responses, are also involved in oncogenesis. Loss of regulation of the normally
      latent NFkappaB contributes importantly to the deregulated growth, resistance to
      apoptosis and propensity to metastasize observed in many cancers. Thus, pathways
      for activation of NFkappaB are promising targets for new agents that may help to
      prevent or treat cancer. We find that the abnormal secretion of multiple
      cytokines that activate NFkappaB by binding to cell-surface receptors is one of
      the major causes of constitutive NFkappaB activity in cancer. A novel finding is
      that the latent form of TGFbeta, secreted by some of these cells, can activate
      NFkappaB. To understand the basis of this abnormal cytokine secretion, we are
      using forward genetic methods to identify specific causative mutations in cancer
      cells.

PMID- 15492503
TI  - The emerging role of RNA interference in the design of novel therapeutics in
      oncology.
AB  - RNA interference (RNAi) has emerged as the tool of choice for studying gene
      function. Dubbed the "breakthrough of the year" in 2002 by the journal Science,
      RNAi is a naturally occurring host defense mechanism that mediates the sequence
      specific degradation of target mRNA transcripts and their protein products. The
      specificity of RNAi makes it an ideal tool for targeted therapeutics against
      unique fusion oncogene sequences. RNAi may also be effective against viral
      mediated oncogenesis and has the potential to enhance tumor sensitivities to
      existing chemotherapy. The current interest in the success of RNAi-based
      therapies will depend on the delivery systems that protect the silencing
      apparatus from endogenous nucleases, sustain tissue-specific expression of the
      small-interfering RNAs, and prevent the activation of a destructive nonspecific
      host immune response.

PMID- 15492505
TI  - Siah: new players in the cellular response to hypoxia.
AB  - Prolyl-hydroxylation of HIF-1alpha is a prerequisite for pVHL binding to HIF
      1alpha, which results in degradation of HIF-1alpha by the ubiquitin-proteasome
      pathway. Hydroxylation of HIF-1alpha is mediated by the family of prolyl
      hydroxylase proteins (PHD). In hypoxia, HIF-1alpha is stabilized as a result of
      inhibition of HIF-1alpha hydroxylation, which in part is achieved by decreased
      activity of PHD enzymes at very low oxygen concentrations. We recently
      demonstrated that in hypoxia the stability of 2 of 3 PHDs (1 and 3) is regulated
      by the E3 ligases Siah1/2. Consequently, in hypoxia Siah determines the
      availability of PHD1/3, which otherwise modify HIF-1alpha to enable its
      association-dependent degradation by pVHL. These findings define a newly
      discovered layer in the regulation of HIF-1alpha in hypoxia. The roles of Siah
      activities in hypoxia responses are discussed.

PMID- 15492504
TI  - Initiation of mRNA translation in oncogenesis: the role of eIF4E.
AB  - The eukaryotic initiation factor 4E (eIF4E) is a key regulator of protein
      translation whose function is activated by the Akt and Ras proto-oncogenic signal
      transduction pathways. eIF4E enhances the translation of mRNAs encoding several
      genes involved in tumorigenesis and acts as a proto-oncogene, in vitro, when
      overexpressed in immortalized cells. Importantly, eIF4E is frequently found
      overexpressed in human cancers of multiple histological origins. However, in vivo
      evidence of the eIF4E neoplastic potential was lacking until now. Here we discuss
      recent findings that demonstrate eIF4E's oncogenic role in vivo through direct
      genetic approaches in the mouse, and identify novel oncogenic functions for this
      initiation factor in cooperative tumorigenesis and response to therapy.

PMID- 15492506
TI  - Restoration of G1/S arrest in E1A+c-Ha-ras-transformed cells by Bcl-2
      overexpression.
AB  - Here we show that introduction of human bcl-2 gene into E1A+c-Ha-ras-transformed
      rat embryo fibroblasts, which are highly susceptible to proapoptotic stimuli and
      fail to be arrested at the G(1)/S boundary following genotoxic stresses, results
      not only in inhibition of apoptosis, but also in restoration of the G(1)/S
      arrest. Overexpression of Bcl-2 did not affect proliferation rate and saturation
      density of E1A+c-Ha-ras transformants. Genotoxic stresses caused prolong G(1)/S
      arrest in Bcl-2-overexpressing transformants. Remarkably, levels and activities
      of Cdk2, cyclins E/A, cyclin E-Cdk2 and cyclin A-Cdk2 were unchanged during
      G(1)/S arrest. Introduction of Bcl-2 into E1A+c-Ha-ras-transformants resulted in
      accumulation of p21/Waf-1 without inhibiting cyclin-Cdk complexes. In both
      parental and Bcl-2-overexpressing cells, p21/Waf-1 was coimmunoprecipitated with
      ERK 1,2 and JNK 1,2, whereas p38 was found in complexes with p21/Waf-1 only in
      Bcl-2-overexpressing transformants. JNK 1,2 and p38 but not ERK 1,2 were detected
      in complexes with the exogenous Bcl-2. However, Bcl-2 did not affect
      phosphorylation of ERK 1,2, JNK 1,2 and p38. G(1)/S arrest induced by adriamycin
      and serum withdrawal (but not by IR) was accompanied by release of active forms
      of p38 from complexes with Bcl-2. We suggest that Bcl-2 restores stress-induced
      G(1)/S arrest without inhibiting cyclin-Cdk2 complexes and MAPK pathways.

PMID- 15492507
TI  - The importance of genome architecture in cancer susceptibility: location,
      location, location.
AB  - Tumorigenesis requires the interaction between different gene disruptions to
      convert a normal cell into a cancer cell. These gene disruptions can involve loss
      of expression or misexpression of genes through genetic or epigenetic mutations.
      It is becoming clear that these disruptions are not isolated events in the
      genome, but are affected by genome architecture and the syntenic relationship of
      alleles on chromosomes. A better understanding of the genetic and epigenetic
      changes in cancer is important for the rational design of new therapies. We have
      recently shown that background-specific polymorphisms and loci under epigenetic
      regulation have a strong effect on cancer susceptibility in a mouse model of
      astrocytoma. Although these mice carry mutations in p53 and ras signaling
      pathways (through mutation of the rasGAP protein, Nf1), the susceptibility to
      different tumor types depends strongly on epigenetic regulation and does not show
      simple Mendelian inheritance. Our results demonstrate the importance of genome
      architecture and how tumorigenesis can be accelerated by concomitant loss or gain
      of multiple genes in a single chromosome rearrangement. Because genome
      architecture is very different between mice and humans, comparing patterns of
      genomic rearrangement in human cancer and mouse models may help distinguish
      causal genomic changes from correlative changes.

PMID- 15492508
TI  - Gene expression profile at the G1/S transition of liver regeneration after
      partial hepatectomy in mice.
AB  - Liver is a quiescent organ with >90% of the cells present in the G(0) stage of
      the cell cycle. However, adult hepatocytes have enormous ability to proliferate
      in response to liver injury. After 70% liver resection hepatocytes enter the cell
      cycle in a highly synchronized manner and undergo 1 to 2 rounds of cell division
      to restore the lost organ mass, thus, representing one of the most reliable model
      systems to study cell cycle progression in vivo. Using high density
      oligonucleotide micro-array we analyzed the expression patterns of genes at the
      G(1)/S transition of liver regeneration in comparison to quiescent livers. The
      G(1)/S boundary was identified by in vivo BrdU pulse labeling and we observed 199
      genes/ESTs which were either up/down regulated at this time point. These
      differentially regulated genes have a wide range of functions including
      transcriptional regulation, signal transduction, cell cycle regulation, chromatin
      reorganization, protein targeting, metabolism, transport, surface receptors,
      circadian rhythms, xenobiotic metabolism, inflammation and acute phase response.
      The functions of most of the genes identified in this screen are not known in the
      process of liver regeneration and cell cycle control at G(1)/S transition.

PMID- 15492509
TI  - Brca1-deficient murine mammary epithelial cells have increased sensitivity to
      CDDP and MMS.
AB  - In this report we describe the isolation of an isogenic pair of Brca1(++) and
      Brca1(-/-) murine mammary epithelial cells (MMECs). These cells were isolated
      from Brca1 conditional knock out mice which contained loxP sites flanking exon 11
      of the Brca1 gene (Brca1(fl/f1)) and then immortalized by infection with HPV-16E6
      retrovirus to degrade p53 protein. Brca1(-/-) MMECs were generated by deletion of
      exon 11 following transduction of Brca1(fl/f1) MMECs with a retroviral vector
      expressing Cre recombinase. Brca1-deficiency rendered MMECs sensitive to cis
      platinum (II) diamine dichloride (CDDP) and methylmethane sulfonate (MMS). The
      Brca1(+/+) and Brca1(-/-) MMECS is the only known pair of isogenic mammary
      epithelial cell lines. The understanding of the mechanisms of the CDDP
      sensitivity of the BRCA1-deficient mammary epithelial cells would be very
      important in understanding how BRCA1-deficiency plays out in tissue specific
      breast cancer chemotherapy. These studies support the role of BRCA1 in the CDDP
      induced and MMS-induced DNA damage and repair by p53-independent pathways.

PMID- 15492511
TI  - Checkpoint adaptation and recovery: back with Polo after the break.
AB  - S. cerevisiae cells that are unable to repair a double strand break ultimately
      escape the DNA damage checkpoint arrest and enter mitosis. This process called
      'adaptation' depends on functional Cdc5, a Polo-like kinase, and was long thought
      to be limited to single-cell organisms. However, the recent finding that Xenopus
      extracts can adapt to a long-lasting stall in DNA replication indicates that
      checkpoint adaptation does also occur in multicellular organisms. Interestingly,
      the Xenopus Polo-like kinase (Plx1) plays an important role in this adaptation.
      To add to this, data from our laboratory have shown that the human Polo-like
      kinase (Plk1) is also required for cell cycle reentry following a DNA damage
      induced arrest. But here, Plk1 was shown to be required for bona-fide checkpoint
      recovery, rather than adaptation. That is, Plk1 is required to restart the cell
      cycle once all of the damage is repaired and checkpoint signaling is turned off.
      While the target of Plx1 during adaptation is a component of the checkpoint
      machinery (Claspin), the target of Plk1 during recovery turns out to be a mitotic
      regulator (Wee1). Here, we discuss some of the remarkable similarities and subtle
      differences in the molecular mechanisms that control checkpoint adaptation and
      recovery, and the role of Polo-like kinases therein.

PMID- 15492510
TI  - BCR/ABL recruits p53 tumor suppressor protein to induce drug resistance.
AB  - Tumors expressing the ABL oncoproteins (BCR/ABL, TEL/ABL, v-ABL) can avoid
      apoptosis triggered by DNA damaging agents. The tumor suppressor protein p53 is
      an important activator of apoptosis in normal cells; conversely its functional
      loss may cause drug resistance. The ABL oncoprotein-p53 paradigm represents the
      relationship between an oncogenic tyrosine kinase and a tumor suppressor gene.
      Here we show that BCR/ABL oncoproteins employ p53 to induce resistance to DNA
      damage in myeloid leukemia cells. Cells transformed by the ABL oncoproteins
      displayed accumulation of p53 upon DNA damage. In contrast, only a modest
      increase of p53 expression followed by activation of caspase-3 were detected in
      normal cells expressing endogenous c-ABL. Phosphatidylinositol-3 kinase-like
      protein kinases (ATR and also ATM) -dependent phosphorylation of p53-Ser15
      residue was associated with the accumulation of p53, and stimulation of p21(Waf
      1) and GADD45, resulting in G(2)/M delay in BCR/ABL cells after genotoxic
      treatment. Inhibition of p53 by siRNA or by the temperature-sensitive mutation
      reduced G(2)/M accumulation and drug resistance of BCR/ABL cells. In conclusion,
      accumulation of the p53 protein contributed to prolonged G(2)/M checkpoint
      activation and drug resistance in myeloid cells expressing the BCR/ABL
      oncoproteins.

PMID- 15492512
TI  - A model for CDK2 in maintaining genomic stability.
AB  - Abundant CDK2/cyclin A activity is present in human cancer cells, suggesting that
      rapid S phase CDK2 inhibition would be an effective anti-cancer approach. The
      dynamic change of chromatin-loading and -dissociation of MCM proteins requires S
      phase CDK2 activity. CDK2 inhibition during replication leads to increased MCM
      complex association with DNA and triggers rereplication. Overreplication-induced
      DSB and RPA-ssDNA intermediates activate ATM and ATR, resulting in a p53 response
      which selectively deletes cells with unresolved rereplication.

PMID- 15492513
TI  - "The dogs that did not bark".

PMID- 15492515
TI  - Who's at fault?

PMID- 15492514
TI  - Lesbian and gay youths at risk.

PMID- 15492517
TI  - More on injection technique.

PMID- 15492519
TI  - Skin necrosis.

PMID- 15492522
TI  - Those long, long hours.

PMID- 15492524
TI  - Women with HIV.

PMID- 15492523
TI  - 15th International AIDS Conference.

PMID- 15492525
TI  - Benzodiazepines, barbiturates, and nursing interventions.

PMID- 15492526
TI  - Introducing the Clinical Nurse Leader.

PMID- 15492527
TI  - Mandatory BSNs?

PMID- 15492528
TI  - The Supreme Court finds for HMOs.

PMID- 15492529
TI  - Health care workers: few feel the flu shot.

PMID- 15492530
TI  - Avlimil taken for female sexual dysfunction.

PMID- 15492531
TI  - House offers small increase for nursing education.

PMID- 15492533
TI  - Medical errors bill advances.

PMID- 15492534
TI  - Influenza 2004-2005: what's new with the flu?

PMID- 15492535
TI  - Victorious existence.

PMID- 15492536
TI  - Presentation of illness in older adults.
AB  - Although people age at different rates, changes to the composition of the human
      body are a hallmark of aging. As a result of such changes, disease can present
      differently in a person over 65 years old than it would in a younger adult or
      child. This article identifies the critical indicators of underlying conditions,
      including changes in mental status, loss of function, decrease in appetite,
      dehydration, falls, pain, dizziness, and incontinence. It also describes the
      presentation of diseases common to older adults, including depression, infection,
      cardiac disease, gastrointestinal disorders, thyroid disease, and type 2
      diabetes.

PMID- 15492538
TI  - "The fear is still in me": caring for survivors of torture.

PMID- 15492540
TI  - Hyperkalemia.

PMID- 15492545
TI  - On the rebound.

PMID- 15492546
TI  - "Dying to tell?".

PMID- 15492547
TI  - Readiness for HIV treatment.

PMID- 15492548
TI  - Women and children first.

PMID- 15492550
TI  - Keeping the comfort.

PMID- 15492551
TI  - A culture of safety.

PMID- 15492552
TI  - Pylorus preserving pancreaticoduodenectomy versus standard Whipple procedure: a
      prospective, randomized, multicenter analysis of 170 patients with pancreatic and
      periampullary tumors.
AB  - OBJECTIVE: A prospective randomized multicenter study was performed to assess
      whether the results of pylorus-preserving pancreaticoduodenectomy (PPPD) equal
      those of the standard Whipple (SW) operation, especially with respect to duration
      of surgery, blood loss, hospital stay, delayed gastric emptying (DGE), and
      survival. SUMMARY BACKGROUND DATA: PPPD has been associated with a higher
      incidence of delayed gastric emptying, resulting in a prolonged period of
      postoperative nasogastric suctioning. Another criticism of the pylorus-preserving
      pancreaticoduodenectomy for patients with a malignancy is the radicalness of the
      resection. On the other hand, PPPD might be associated with a shorter operation
      time and less blood loss. METHODS: A prospective randomized multicenter study was
      performed in a nonselected series of 170 consecutive patients. All patients with
      suspicion of pancreatic or periampullary tumor were included and randomized for a
      SW or a PPPD resection. Data concerning patients' demographics, intraoperative
      and histologic findings, as well as postoperative mortality, morbidity, and
      follow-up up to 115 months after discharge, were analyzed. RESULTS: There were no
      significant differences noted in age, sex distribution, tumor localization, and
      staging. There were no differences in median blood loss and duration of operation
      between the 2 techniques. DGE was observed equally in the 2 groups. There was
      only a marginal difference in postoperative weight loss in favor of the standard
      Whipple procedure. Overall operative mortality was 5.3%. Tumor positive resection
      margins were found for 12 patients of the SW group and 19 patients of the PPPD
      group (P < 0.23). Long-term follow-up showed no significant statistical
      differences in survival between the 2 groups (P < 0.90). CONCLUSIONS: The SW and
      PPPD operations were associated with comparable operation time, blood loss,
      hospital stay, mortality, morbidity, and incidence of DGE. The overall long-term
      and disease-free survival was comparable in both groups. Both surgical procedures
      are equally effective for the treatment of pancreatic and periampullary
      carcinoma.

PMID- 15492553
TI  - Save the pylori.

PMID- 15492554
TI  - Tissue-engineered small intestine improves recovery after massive small bowel
      resection.
AB  - OBJECTIVE: Rescue with tissue-engineered small intestine (TESI) after massive
      small bowel resection (MSBR). SUMMARY BACKGROUND DATA: Short bowel syndrome is a
      morbid product of massive small bowel resection. We report the first replacement
      of a vital organ by tissue engineering with TESI after MSBR. METHODS: Ten male
      Lewis rats underwent TESI implantation with green fluorescent protein (GFP)
      marked cells (TESI+, n = 5) or sham laparotomy (TESI-, n = 5) followed by MSBR.
      Side-to-side anastomosis of TESI to proximal small intestine was performed or
      omitted. TESIO animals underwent implantation of engineered intestine with no
      further surgery. Weights were measured QOD until day 40. Transit times were
      measured. DNA assay was performed with computer morphometry. Northern blots of
      RNA were probed for intestinal alkaline phosphatase (IAP) and villin. Hematoxylin
      and eosin, S100, and smooth muscle actin immunohistochemistry were performed.
      Blood was collected at sacrifice. RESULTS: All 10 rats initially lost then
      regained weight. The initial rate of weight loss was higher in TESI+ versus TESI
      , but the nadir was reached a week earlier with more rapid weight gain
      subsequently to 98% preoperative weight on day 40 in animals with engineered
      intestine versus 76% (P < 0.03). Serum B12 was higher at 439 pg/mL versus 195.4
      pg/mL. IAP mRNA appeared greater in TESI+ than TESIO, with constant villin
      levels. Histology revealed appropriate architecture including nerve. GFP labeling
      persisted. CONCLUSIONS: Anastomosis of TESI significantly improved postoperative
      weight and B12 absorption after MSBR. IAP, a marker of differentiation in
      intestinal epithelium, is present in TESI, and GFP labeling was accomplished.

PMID- 15492555
TI  - Tissue engineered small intestine: a viable clinical option?

PMID- 15492557
TI  - Meta-analysis of laparoscopic versus open pyloromyotomy.
AB  - OBJECTIVE: To perform a meta-analysis of studies comparing open pyloromyotomy
      (OP) and laparoscopic pyloromyotomy (LP) in the treatment of infantile
      hypertrophic pyloric stenosis. BACKGROUND: LP has become increasingly popular for
      the management of pyloric stenosis. Despite a decade of experience, the real
      benefit of LP over the open procedure remains unclear. METHODS: Using a defined
      search strategy, studies directly comparing OP with LP were identified (n = 8).
      Data for infants treated by both approaches were extracted and used in our meta
      analysis. OP and LP were compared in terms of complications, efficacy, operating
      time, and recovery time. Weighted mean difference (WMD) between continuous
      variables and 95% confidence intervals (95% CI) were calculated. For dichotomous
      data, relative risk (RR) and 95% CI were determined. RESULTS: Only 3 studies were
      prospective, and just 1 study was a prospective randomized controlled trial.
      Mucosal perforations and incomplete pyloromyotomy were both more common with LP.
      Compared with OP, LP is associated with higher complication rate (RR 0.81 [0.5,
      1.29], P = 0.4), similar operating time (WMD 1.52 minutes [-0.26, 3.29], P =
      0.09), shorter time to full feeds (WMD 8.66 hours [7.25, 10.07], P < 0.00001),
      and shorter postoperative length of stay (WMD 7.03 hours [3.74, 10.32], P =
      0.00003). CONCLUSIONS: OP is associated with fewer complications and higher
      efficacy. Recovery time appears significantly shorter following LP. A prospective
      randomized controlled trial is warranted to fully investigate these and other
      outcome measures.

PMID- 15492558
TI  - Living related small bowel transplantation: donor surgical technique.
AB  - OBJECTIVE: To describe a standardized technique for ileal graft procurement in
      the setting of living related bowel transplantation. SUMMARY BACKGROUND DATA:
      Living donor transplantation has been successfully developed for kidney, liver,
      pancreas, and lung transplantation. More recently, living related small bowel
      transplantation (LR-SBTx) has been developed with the aim of expanding the pool
      of intestinal graft donors and reducing the mortality in patients on the waiting
      list. To date, a total of 25 LR-SBTx worldwide have been reported to the
      international registry. We herein report the largest single center experience.
      METHODS: A segment of ileum, 150 to 200 cm, is resected 20 cm proximal to the
      ileocecal valve (ICV), which is always preserved. The arterial inflow is given by
      the terminal branch of the superior mesenteric artery and venous outflow by a
      proximal segment of the superior mesenteric vein. The entire bowel is measured
      intraoperatively and at least 60% of intestine length is left in the donor.
      RESULTS: Since 1998, we have performed 9 terminal ileum resections for small
      bowel donation. None of the donors has experienced persistent alteration of bowel
      habits or malabsorption; only 1 minor wound complication has occurred.
      CONCLUSIONS: Terminal ileal resection with preservation of the ICV seems to
      assure fast functional recovery of the donor and has minimal postoperative
      complications.

PMID- 15492559
TI  - Gastric emptying and vagus nerve function after laparoscopic partial
      fundoplication.
AB  - OBJECTIVE: To establish the relation between vagus nerve dysfunction, gastric
      emptying, and antireflux surgery. SUMMARY BACKGROUND DATA: Delayed gastric
      emptying occurs in up to 40% of reflux patients. After antireflux surgery,
      gastric emptying becomes normal or is even accelerated. Occasionally, severe
      gastric stasis is found and is associated with a negative outcome of the
      antireflux procedure. It has been suggested that injury to the vagus nerve could
      be the cause of this delayed emptying. METHODS: We evaluated in a prospective
      study gastric emptying of solids and vagus nerve function (pancreatic polypeptide
      response to hypoglycemia) before and after surgery in 41 patients (22 women; age
      43 +/- 1.6 years) who underwent laparoscopic hemifundoplication. RESULTS: All
      patients had relief of reflux symptoms varying from adequate (n = 8) to complete
      relief (n = 33). Gastric emptying of solids increased significantly (P < 0.001)
      after operation: lag phase from 19 +/- 2 to 10 +/- 1 minute, emptying rate (%/h)
      from 37 +/- 2 to 48 +/- 5 and half emptying time from 110 +/- 8 to 81 +/- 4
      minutes. Gastric emptying improved to a similar extent in patients with delayed
      and normal preoperative gastric emptying. Postoperative signs of vagus nerve
      damage (PP peak < 47pmol/L) were present in 4 patients (10%). In these 4 patients
      gastric emptying both before and after operation did not differ from patients
      with normal vagus nerve function. In fact, none of the 41 patients had severely
      delayed emptying after laparoscopic hemifundoplication. CONCLUSIONS: Laparoscopic
      hemifundoplication affects vagus nerve integrity in 10% of patients, but this
      does not lead to a delay in gastric emptying. In fact, gastric emptying improved
      significantly after fundoplication.

PMID- 15492556
TI  - Resolved and unresolved controversies in the surgical management of patients with
      Zollinger-Ellison syndrome.
AB  - OBJECTIVE: Highlight unresolved controversies in the management of Zollinger
      Ellison syndrome (ZES). SUMMARY BACKGROUND DATA: Recent studies have resolved
      some of the previous controversies including the surgical cure rate in patients
      with and without Multiple Endocrine Neoplasia-type1 (MEN1), the biological
      behavior of duodenal and pancreatic gastrinomas, role of imaging studies to
      localize tumor, and gastrectomy to manage acid output. METHODS: Review of the
      literature based on computer searches in Index Medicus, Pubmed and Ovid. RESULTS:
      Current controversies as identified in the literature include the role of
      endoscopic ultrasound (EUS), surgery in ZES patients with MEN1,
      pancreaticoduodenectomy (Whipple procedure), lymph node primary gastrinoma,
      parietal cell vagotomy, reoperation and surgery for metastatic tumor, and the use
      of minimally invasive surgical techniques to localize and remove gastrinoma.
      CONCLUSIONS: It is hoped that future studies will focus on these issues to
      improve the surgical management of ZES patients.

PMID- 15492560
TI  - Predictive factors for postoperative pulmonary complications and mortality after
      esophagectomy for cancer.
AB  - OBJECTIVE: This study aimed at: (1) documenting the evolution of surgical results
      of esophagectomy in a high-volume center, (2) identifying predictive factors of
      pulmonary complications and mortality, and (3) examining whether preoperative
      chemoradiation therapy would complicate postoperative recovery. SUMMARY
      BACKGROUND DATA: Pulmonary complications and mortality rate after esophagectomy
      remain substantial, and factors responsible have not been adequately studied.
      Neoadjuvant chemoradiation is widely used; it is hypothesized that this may lead
      to adverse postoperative outcome. METHODS: Prospectively collected data were used
      to analyze outcome in 421 patients with intrathoracic squamous cell esophageal
      cancer who underwent resection. Logistic regression analyses determined
      independent predictors of pulmonary complications and death. Two time periods
      were compared: period I (January 1990 to June 1995) and period II (July 1995 to
      December 2001). In the later period, neoadjuvant chemoradiation therapy was
      introduced. RESULTS: Transthoracic resections were carried out in 83% of
      patients. Neoadjuvant chemoradiation was given to 42% of patients in period II.
      Major pulmonary complications occurred in 15.9%, and were primarily responsible
      for 55% of hospital deaths. Thirty-day and hospital mortality rates were 1.4% and
      4.8%, respectively. Logistic regression analysis identified age, operation
      duration, and proximal tumor location as risk factors for pulmonary
      complications, whereas advanced age and higher blood loss were predictive of
      mortality. Chemoradiation did not lead to worse outcome. When period I and II
      were compared, hospital mortality rate reduced from 7.8% to 1.1%, P = 0.001, with
      correspondingly less blood loss (median blood loss was 700 ml (range: 200-2700
      (period I) and 450 ml (range: 100-7000) (period II), P < 0.01). CONCLUSION: A
      1.1% mortality rate was achieved in the last 6 years of the study period.
      Preoperative chemoradiation did not result in worse outcome. Reduction in
      mortality rate correlated with decreased blood loss.

PMID- 15492561
TI  - Treatment of thoracic anastomotic leaks after esophagectomy with self-expanding
      plastic stents.
AB  - OBJECTIVE: To evaluate the efficacy of a self-expanding plastic stent in the
      treatment of thoracic leaks after esophagectomy for cancer. SUMMARY BACKGROUND
      DATA: Anastomotic leaks are a major cause of morbidity and mortality after
      esophageal resection. Treatment options range from aggressive surgery to
      conservative management, but there remains much controversy on the best
      treatment. METHODS: Over a 6-year period (1998-2003), esophagogastric leaks were
      observed in 19 of 204 patients (9.3%) after esophagectomy. Between 1998 and 2000,
      anastomotic leaks were managed by reexploration (n = 7) or by conservative
      treatment (n = 3). Since 2001, insertion of self-expanding plastic stents was
      performed for all anastomotic leaks (n = 9). The short-term efficacy and long
      term outcome of both treatments were analyzed. RESULTS: Self-expanding plastic
      stents were successfully placed in all patients without procedure-related
      morbidity. Immediate leak occlusion was obtained in 8 of 9 patients. The mean
      healing time (time to stent removal) was 29 days. Compared with the conventional
      treatment group, patients who were treated with stents had earlier oral intake
      (11 days versus 23 days), a less extensive intensive care course (25 days versus
      47 days), and shorter hospital stay (35 days versus 57 days). In-hospital
      mortality was 0% (0 of 9 patients) in the stent group and 20% (2 of 10 patients)
      in the other group. After a mean follow-up of 12 months, none of the patients
      developed a stricture after stenting, but a stricture occurred in 1 patient after
      conservative treatment. CONCLUSIONS: Self-expanding plastic stents can reduce
      leak-related morbidity and mortality after esophagectomy and may be considered a
      cost-effective treatment alternative.

PMID- 15492562
TI  - Patterns of initial recurrence in completely resected gastric adenocarcinoma.
AB  - OBJECTIVE: To review recurrence patterns in completely resected gastric
      adenocarcinoma. SUMMARY BACKGROUND DATA: Despite improvements in the surgical
      treatment of gastric adenocarcinoma, recurrence rates remain high in patients
      with advanced stage disease. Understanding the timing and patterns of recurrence
      is essential to develop effective adjuvant treatment strategies. METHODS: A
      retrospective review of a prospectively maintained gastric cancer database was
      carried out. The timing and pattern of recurrence were reviewed. Univariate and
      multivariate analyses were performed to identify factors predictive of recurrence
      patterns. RESULTS: From July 1985 through June 2000, 1172 patients underwent an
      R0 resection. Of these, 496 (42%) had recurrence and complete data on recurrence
      could be obtained in 367 patients (74%). Among the documented recurrences, 79%
      were detected within 2 years of operation. Locoregional sites were involved as
      any part of the recurrence pattern in 199 patients (54%). Distant sites were
      involved as any part of the recurrence in 188 patients (51%) and peritoneal
      recurrence was detected as any part of the recurrence in 108 patients (29%). On
      multivariate analysis, peritoneal recurrence was associated with female gender,
      advanced T-stage, and distal and diffuse type tumors; locoregional recurrence was
      associated with male gender and proximal location; distant recurrence was
      associated with proximal location, early T stage, and intestinal type tumors. The
      median time to death from the time of recurrence was 6 months. CONCLUSIONS:
      Recurrence after complete resection of gastric adenocarcinoma usually occurs
      within 2 years and is rapidly fatal. Patterns of recurrence are variable and may
      be associated with specific clinicopathologic factors.

PMID- 15492563
TI  - Association of laryngeal cancer with previous gastric resection.
AB  - OBJECTIVE: To investigate the association between gastric surgery and cancer of
      the larynx. SUMMARY BACKGROUND DATA: Biliary reflux is frequent after gastric
      surgery and may reach the proximal segment of the esophagus and the larynx. It is
      possible that duodenal content (consisting in bile acids, trypsin), together with
      pepsin and acid residues when gastric resection is partial, may cause harmful
      action on the multistratified epithelium of the larynx. METHODS: A retrospective
      case-control study on subjects admitted between January 1987 and May 2002 in the
      same hospital in Rome was carried out. The study included 828 consecutive
      patients with laryngeal cancer (cases) and 825 controls with acute myocardial
      infarction. Controls were randomly sampled out of a total of 10,000 and matched
      with cases for age, sex, and year of admission. Logistic regression models were
      used to assess the role of gastric resection in determining laryngeal cancer risk
      while controlling for potential confounding factors. RESULTS: Previous
      gastrectomy was reported by 8.1% of cases and 1.8% of the controls (P < 0.0001).
      A 4-fold association emerged between gastric surgery and laryngeal cancer risk
      (adjusted OR = 4.3, 95% CI: 2.4-7.9). The risk appeared strongly increased 20
      years after surgery (OR = 14.8, 95% CI: 3.4-64.6). Heavy alcohol drinking (OR =
      2.5, 95% CI: 1.8-3.5), smoking (OR = 4.7, 95% CI: 3.3-6.7), and blue-collar
      occupation (OR = 4.6, 95% CI: 3.2-6.7) were all independently associated with the
      risk of laryngeal cancer. CONCLUSIONS: Previous gastric surgery is associated
      with an increased risk of laryngeal cancer. A periodic laryngeal examination
      should be considered in long-term follow-up of patients with gastric resection.

PMID- 15492564
TI  - Clinical outcome and factors predictive of recurrence after enterocutaneous
      fistula surgery.
AB  - OBJECTIVE: Recent experience with surgery for enterocutaneous fistulae (ECF) at a
      specialist colorectal unit is reviewed to define factors relating to a successful
      surgical outcome. SUMMARY BACKGROUND DATA: ECF cause significant morbidity and
      mortality and need experienced surgical management. Previous publications have
      concentrated on mortality resulting from fistulae, while factors affecting
      recurrence have not previously been a focus of analysis. METHODS: Records were
      reviewed of patients who had ECF surgery (1994-2001). Management strategy
      involved early drainage of sepsis and nutritional support prior to elective ECF
      repair, with selective defunctioning proximal stoma formation. RESULTS: A total
      of 205 patients were available (89 males, 43%; median age, 51 years; range, 16
      86) years). ECF were related to Crohn's disease in 95, ulcerative colitis in 18,
      diverticular disease in 17, carcinoma in 25 (16 after radiotherapy), mesh ventral
      hernia repair in 21, and other causes in 29. Forty-one (20%) had undergone
      attempted fistula repair at other institutions. Initial management included CT
      guided drainage of an intra-abdominal abscess in 23 patients, and total
      parenteral nutrition in 74 (36%). A total of 203 patients had definitive ECF
      repair. Forty-four had oversewing or wedge resection of the fistula, and 159 had
      resection and reanastomosis of the involved small bowel segment or ileocolic
      anastomosis. Ninety-day operative mortality was 3.5%. A total of 42 (20.5%)
      patients developed ECF recurrence within 3 months. Multivariate analysis
      demonstrated that recurrence was more likely after oversewing (36%) than
      resection (16%, P = 0.006). CONCLUSIONS: A strategy of drainage of acute sepsis,
      maintenance of nutritional support prior to surgery, and selective use of PS
      allows for primary closure in 80% of complicated ECF. Resection should be
      performed when feasible.

PMID- 15492565
TI  - A new prognostic staging system for rectal cancer.
AB  - OBJECTIVE: To clarify the appropriateness of tumor "budding," a quantifiable
      histologic variable, as 1 parameter in the construction of a new prognostic
      grading system for rectal cancer. SUMMARY BACKGROUND DATA: Patient division
      according to an accurate prognostic prediction could enhance the effectiveness of
      postoperative adjuvant therapy and follow-up. PATIENTS AND METHODS: Tumor budding
      was defined as an isolated cancer cell or a cluster composed of fewer than 5
      cells in the invasive frontal region, and was divided into 2 grades based on its
      number within a microscopic field of x250. We analyzed 2 discrete cohorts
      comprising 638 and 476 patients undergoing potentially curative surgery. RESULTS:
      In the first cohort, high-grade budding (10 or more foci in a field) was observed
      in 30% of patients and was significantly associated with a lower 5-year survival
      rate (41%) than low-grade budding (84%). Similarly, in the second cohort, the 5
      year survival rate was 43% in high-grade budding patients and 83% in low-grade
      budding patients. In both cohorts, multivariate analyses verified budding to be
      an independent prognosticator, together with nodal involvement and extramural
      spread. These 3 variables were given weighted scores, and the score range was
      divided to provide 5 prognostic groups (97%; 86%; 61%; 39%; 17% 5-year survival).
      The model was tested on the second cohort, and similar prognostic results were
      obtained. CONCLUSIONS: We propose that because of its relevance to prognosis and
      its reproducibility, budding is an excellent parameter for use in a grading
      system to provide a confident prediction of clinical outcome.

PMID- 15492566
TI  - Clinical significance of dihydropyrimidine dehydrogenase in adjuvant 5
      fluorouracil liver perfusion chemotherapy for pancreatic cancer.
AB  - OBJECTIVE: To clarify the relationship between intratumoral dihydropyrimidine
      dehydrogenase (DPD) expression and response to 5-fluorouracil (5-FU) liver
      perfusion chemotherapy (LPC) in pancreatic cancer patients, we evaluated DPD
      expression immunohistochemically in resected pancreatic cancer tissues. SUMMARY
      BACKGROUND DATA: Pancreatic cancer is considered a disease with a poor prognosis
      even if aggressive resection is performed. One of the main causes of death is
      hepatic metastasis soon after surgery. As a treatment, we have assessed adjuvant
      LPC via the portal vein using 5-FU just after pancreatectomy for advanced
      pancreatic cancer since 1994. However, the results remain unsatisfying. METHODS:
      Sixty-eight resected specimens were obtained from patients with pancreatic cancer
      from 1988 to 2000. Formalin-fixed paraffin-embedded tissues were immunostained
      with polyclonal anti-DPD antibody. The relation between intratumoral DPD
      expression and the prognoses of pancreatic cancer patients was investigated
      statistically. RESULTS: Of the 68 tumors studied, 27 carcinomas (39.7%) were
      DPD(+), and 41 (60.3%) were DPD(-). In the DPD(+) group, there was no significant
      difference between the LPC(+) and LPC(-) subgroups, whereas in the DPD(-) group
      the LPC(+) subgroup showed a significantly higher survival rate than the LPC(-)
      subgroup. Moreover, in the LPC(+) group, overall survival in the DPD(-) subgroup
      was significantly better than in the DPD(+) subgroup. CONCLUSIONS: An
      immunohistochemical evaluation of intratumoral DPD expression might be useful in
      predicting responsiveness to 5-FU-based chemotherapy in pancreatic cancer
      patients. In the DPD(-) group, liver perfusion chemotherapy using 5-FU via the
      portal vein is effective adjuvant therapy for pancreatic cancer once
      pancreatectomy has been performed.

PMID- 15492567
TI  - Gastric decompression and enteral feeding through a double-lumen
      gastrojejunostomy tube improves outcomes after pancreaticoduodenectomy.
AB  - OBJECTIVE: The objective of this study was to assess the feasibility and safety
      of inserting a double-lumen gastrojejunostomy tube (GJT) after
      pancreaticoduodenectomy (PD) and to evaluate associated outcomes. BACKGROUND:
      Gastroparesis is a frequent postoperative event following PD. This often
      necessitates prolonged gastric decompression and nutritional support. A double
      lumen GJT may be particularly useful in this situation: gastric decompression may
      be achieved through the gastric port without a nasogastric tube; enteral feeding
      may be administered through the jejunal port. METHODS: Thirty-six patients with
      periampullary tumors were randomized at the time of PD to insertion of GJT or to
      the routine care of the operating surgeon. Outcomes, including length of stay,
      complications, and costs, were followed prospectively. RESULTS: The 2 groups had
      similar characteristics. Prolonged gastroparesis occurred in 4 controls (25%) and
      in none of the patients who had a GJT (P = 0.03). Complication rates were similar
      in each group. Mean postoperative length of stay was significantly longer in
      controls compared with patients who had a GJT (15.8 +/- 7.8 days versus 11.5 +/-
      2.9 days, respectively; P = 0.01). Hospital charges were 82,151 +/- 56,632
      dollars in controls and 52,589 +/- 15,964 dollars in the GJT group (P = 0.036).
      CONCLUSIONS: In patients undergoing PD, insertion of a GJT is safe. Moreover,
      insertion of a GJT improves average length of stay. At the time of resection of
      periampullary tumors, GJT insertion should be considered, especially given this
      is a patient population in which weight loss and cachexia are frequent.

PMID- 15492568
TI  - Platelet kinetics and decreased transfusion requirements after splenectomy for
      hematologic malignancy.
AB  - OBJECTIVE: Thrombocytopenia is a significant and morbid problem in patients with
      hematologic malignancy, resulting in frequent platelet transfusions and
      significant resource consumption. We undertook this study to determine the impact
      of splenectomy on transfusion requirements in patients with chronic leukemia,
      acute leukemia, myelodysplastic syndrome, and lymphoma. METHODS: Records of 134
      patients with hematologic malignancies who underwent splenectomy were reviewed.
      Results are reported as mean +/- standard error of the mean. RESULTS: Mean
      preoperative (preop) platelet count was 97 +/- 8 K/microL. A significant rise in
      platelets, compared with preop, was observed starting on postsplenectomy day 1
      (141 +/- 8 K/microL, P < 0.001 versus preop) and persisted through day 7. Counts
      remained significantly elevated at 3 and 6 months and years 1-5. In profoundly
      thrombocytopenic patients (preop levels < 20 K/microL), preop count was 11 +/- 1
      K/microL. A significant postsplenectomy platelet rise persisted for at least 1
      year (137 +/- 52 K/microL, P < 0.05 versus preop). An increased platelet level
      was observed in all hematologic subgroups; in the chronic leukemias (n = 58, P <
      0.01) and in lymphoma (n = 59, P < 0.001), this reached significance. Mean
      platelet transfusions were significantly decreased from preop (3 months preop:
      8.6 +/- 2 units) compared with postsplenectomy (3 months postsplenectomy: 5.0 +/-
      1 unit, P = 0.03). This decrease was even more pronounced in profoundly
      thrombocytopenic patients (31.6 +/- 10.6 units preop versus 8.9 +/- 4.8 units
      postoperative, P = 0.01). CONCLUSIONS: In the hematologic malignancies,
      splenectomy produces a significant and longlasting restoration of platelet levels
      and a resultant decrease in platelet transfusion requirements. These beneficial
      effects of splenectomy hold true even for the most profoundly thrombocytopenic
      patients.

PMID- 15492570
TI  - Lymphedema after complete axillary node dissection for melanoma: assessment using
      a new, objective definition.
AB  - OBJECTIVES: The objectives of this study were to define appropriate criteria for
      assessing the presence of lymphedema, and to report the prevalence and risk
      factors for development of upper limb lymphedema after level I-III axillary
      dissection for melanoma. SUMMARY BACKGROUND DATA: The lack of a consistent and
      reliable objective definition for lymphedema remains a significant barrier to
      appreciating its prevalence after axillary dissection for melanoma (or breast
      carcinoma). METHODS: Lymphedema was assessed in 107 patients (82 male, 25 female)
      who had previously undergone complete level I-III axillary dissection. Of the 107
      patients, 17 had also received postoperative axillary radiotherapy. Arm volume
      was measured using a water displacement technique. Change in volume of the arm on
      the side of the dissection was referenced to the volume of the other (control)
      arm. Volume measurements were corrected for the effect of handedness using
      corrections derived from a control group. Classification and regression tree
      (CART) analysis was used to determine a threshold fractional arm volume increase
      above which volume changes were considered to indicate lymphedema. RESULTS: Based
      on the CART analysis results, lymphedema was defined as an increase in arm volume
      greater than 16% of the volume of the control arm. Using this definition,
      lymphedema prevalence for patients in the present study was 10% after complete
      level I-III axillary dissection for melanoma and 53% after additional axillary
      radiotherapy. Radiotherapy and wound complications were independent risk factors
      for the development of lymphedema. CONCLUSIONS: A suggested objective definition
      for arm lymphedema after axillary dissection is an arm volume increase of greater
      than 16% of the volume of the control arm.

PMID- 15492569
TI  - First and repeat resection of colorectal liver metastases in elderly patients.
AB  - OBJECTIVE: The objective of this study was to evaluate the short- and long-term
      outcome after first and repeat resection in patients older than 70 years. SUMMARY
      BACKGROUND DATA: Liver resection is the best treatment for colorectal liver
      metastases and is currently increasingly performed in elderly patients. The
      benefit of resection for these patients needs to be evaluated. METHODS: Between
      1990 and 2000, 56 first and 16 repeat liver resections were performed in 61
      patients older than 70 years. Patients were identified from a prospective
      database and records were reviewed retrospectively. RESULTS: First and repeat
      liver resection resulted, respectively, in a 0% and 7% postoperative mortality
      rate and a 41% and 38% complication rate, respectively. Median survival after
      first resection of 53 patients with R0 resection was 33 months, and the 5-year
      survival rate was 22%. Factors associated with poor long-term survival in
      multivariate analysis were extrahepatic disease, high carcinoembryonic antigen
      level over 200 ng/mL, and the presence of 3 or more liver metastases. Patients
      without these risk factors showed a median survival of 42 months and a 5-year
      survival rate of 36%. Repeat liver resection resulted in a median survival of 17
      months and in a 3-year survival rate of 25%. CONCLUSION: First and repeat liver
      resection for colorectal liver metastases can be performed safely in patients
      older than 70 years. A 5-year survival rate similar to those of younger patients
      can be expected after first liver resection for patients without the presence of
      risk factors.

PMID- 15492571
TI  - A pentadecapeptide fragment of islet neogenesis-associated protein increases beta
      cell mass and reverses diabetes in C57BL/6J mice.
AB  - OBJECTIVE: The objective of this study was to demonstrate that islet neogenesis
      associated protein (INGAP) peptide, a pentadecapeptide containing the
      biologically active portion of native INGAP, increases functional beta-cell mass
      in normal animals and can be used therapeutically to reverse hyperglycemia in
      streptozotocin-induced diabetes. SUMMARY BACKGROUND DATA: INGAP, a 175 amino acid
      pancreatic acinar cell protein, has been suggested to be implicated in beta-cell
      mass expansion. METHODS: In the first part of this study, normoglycemic hamsters
      were administered either 500 microg INGAP peptide (n = 30) or saline (n = 20)
      intraperitoneally daily and sacrificed after 10 or 30 days of treatment. Blood
      glucose and insulin levels were measured, and a histologic and morphometric
      analysis of the pancreas was performed to determine the effect of INGAP peptide
      on the endocrine pancreas. In the second part of the study, 6- to 8-week-old
      C57BL/6J mice (n = 8) were administered multiple low doses of the beta-cell toxin
      streptozotocin (STZ) inducing insulitis and hyperglycemia. The mice were then
      injected with INGAP peptide (n = 4) or saline (n = 4) for 39 days and sacrificed
      at 48 days. Two additional groups of diabetic mice were administered either a
      peptide composed of a scrambled sequence of amino acids from INGAP peptide (n =
      5) or exendin-4 (n = 5), an incretin that has been associated with amelioration
      of hyperglycemia. RESULTS: Islet cell neogenesis was stimulated in INGAP-treated
      hamsters by 10 days. At 30 days, the foci of new endocrine cells had the
      appearance of mature islets. There was a 75% increase in islet number, with
      normal circulating levels of blood glucose and insulin. Administration of INGAP
      peptide to diabetic mice reversed the diabetic state in all animals, and this was
      associated with increased expression of PDX-1 in duct cells and islet cell
      neogenesis with a reduction of insulitis in the new islets. Diabetic mice treated
      with exendin-4 or a scrambled INGAP peptide did not revert from hyperglycemia.
      CONCLUSION: Because there is a deficiency of beta-cell mass in both type-1 and
      type-2 diabetes, INGAP peptide stimulation of fully functional neoislet
      differentiation may provide a novel approach for diabetes therapy.

PMID- 15492572
TI  - Pancreatic duct ligation reduces lung injury following trauma and hemorrhagic
      shock.
AB  - OBJECTIVE: To determine whether pancreatic digestive enzymes released into the
      ischemic gut during an episode of T/HS are involved in the generation of distant
      organ injury. This hypothesis was tested by examining the effect of PDL on T/HS
      induced intestinal injury, lung injury, and RBC deformability. SUMMARY BACKGROUND
      DATA: The effect of pancreatic duct ligation (PDL) on distant organ injury
      following trauma/hemorrhagic shock (T/HS) was examined. PDL before T/HS decreases
      lung and red blood cell (RBC) injury and exerts a limited protective effect on
      the gut. Pancreatic proteases in the ischemic gut appear to be involved in gut
      induced lung and RBC injury. Based on recent work, it appears that
      proinflammatory and/or toxic factors, which are generated by the ischemic
      intestine, play an important role in the pathogenesis of multiple organ failure.
      The process by which these toxic factors are generated remains unknown. Previous
      experimental work has clearly documented that intraluminal inhibition of
      pancreatic proteases decreases the degree of T/HS-induced lung injury and
      neutrophil activation. One possible explanation for this observation is that the
      toxic factors present in intestinal lymph are byproducts of interactions between
      pancreatic proteases and the ischemic gut. METHODS: Male Sprague-Dawley rats were
      subjected to a laparotomy (trauma) and 90 minutes of sham (T/SS) or T/HS with or
      without PDL. At 3 and 24 hours following resuscitation, animals were killed and
      samples of gut, lung, and blood were collected for analysis. Lung permeability,
      pulmonary myeloperoxidase levels, and bronchoalveolar fluid protein content were
      used to quantitate lung injury. Intestinal injury was determined by histologic
      analysis of terminal ileum (% villi injured). To assess RBC injury, RBC
      deformability was measured, as the RBC elongation index (RBC-EI), using a LORCA
      device. RESULTS: At 3 and 24 hours following resuscitation, PDL prevented shock
      induced increases in lung permeability to both Evans blue dye and protein in
      addition to preventing an increase in pulmonary myeloperoxidase levels. T/HS
      induced impairments in RBC deformability were significantly reduced at both time
      points in the PDL + T/HS group, but deformability did not return to T/SS levels.
      PDL did reduce the magnitude of ileal injury at 3 hours after T/HS, but the
      protective effect was lost at 24 hours after T/HS. CONCLUSIONS: PDL prior to T/HS
      decreases lung injury and improves RBC deformability but exerts a limited
      protective effect on the gut. Thus, the presence of pancreatic digestive enzymes
      in the ischemic gut appears to be involved in gut-induced lung and RBC injury.

PMID- 15492573
TI  - Liberal versus restrictive fluid administration to improve recovery after
      laparoscopic cholecystectomy: a randomized, double-blind study.
AB  - OBJECTIVE: The objective of this study was to investigate the effects of 2 levels
      of intraoperative fluid administration on perioperative physiology and outcome
      after laparoscopic cholecystectomy. SUMMARY BACKGROUND DATA: Intraoperative fluid
      administration is variable as a result of limited knowledge of physiological and
      clinical effects of different fluid substitution regimens. METHODS: In a double
      blind study, 48 ASA I-II patients undergoing laparoscopic cholecystectomy were
      randomized to 15 mL/kg (group 1) or 40 mL/kg (group 2) intraoperative
      administration of lactated Ringer's solution (LR). All other aspects of
      perioperative management as well as preoperative fluid status were standardized.
      Primary outcome parameters were assessed repeatedly for the first 24
      postoperative hours and included pulmonary function (spirometry), exercise
      capacity (submaximal treadmill test), cardiovascular hormonal responses, balance
      function, pain, nausea and vomiting, recovery, and hospital stay. RESULTS:
      Intraoperative administration of 40 mL/kg compared with 15 mL/kg LR led to
      significant improvements in postoperative pulmonary function and exercise
      capacity and a reduced stress response (aldosterone, antidiuretic hormone, and
      angiotensin II). Nausea, general well-being, thirst, dizziness, drowsiness,
      fatigue, and balance function were also significantly improved, as well as
      significantly more patients fulfilled discharge criteria and were discharged on
      the day of surgery with the high-volume fluid substitution. CONCLUSIONS:
      Intraoperative administration of 40 mL/kg compared with 15 mL/kg LR improves
      postoperative organ functions and recovery and shortens hospital stay after
      laparoscopic cholecystectomy.

PMID- 15492574
TI  - Radiofrequency ablation of small hepatocellular carcinoma in cirrhotic patients
      awaiting liver transplantation: a prospective study.
AB  - OBJECTIVE: Determine the histologic response-rate (complete versus partial tumor
      extinction) after single radiofrequency ablation (RFA) of small hepatocellular
      carcinoma (HCC) arising in cirrhosis. Investigate possible predictors of response
      and assess efficacy and safety of RFA as a bridge to liver transplantation (OLT).
      BACKGROUND: RFA has become the elective treatment of local control of HCC,
      although histologic data supporting radiologic assessment of response are rare
      and prospective studies are lacking. Prognostic impact of repeated RFA for HCC
      persistence is also undetermined. METHODS: Percentage of RFA-induced necrosis and
      tumor persistence-rate at various intervals from treatment was studied in 60 HCC
      (median: 3 cm; Milan-Criteria IN: 80%) isolated in 50 consecutive cirrhotic
      patients undergoing OLT. Single-session RFA was the only treatment planned before
      OLT. Histologic response determined on explanted livers was related to 28
      variables and to pre-OLT CT scan. RESULTS: Mean interval RFA-->OLT was 9.5
      months. Post-RFA complete response rate was 55%, rising to 63% for HCC </=3 cm.
      Tumor size was the only prognostic factor significantly related to response (P =
      0.007). Tumor satellites and/or new HCC foci (56 nodules) were unaffected by RFA
      and significantly correlated with HCC >3 cm (P = 0.05). Post-RFA tumor
      persistence probability increased with time (12 months: 59%; 18 months: 70%).
      Radiologic response rate was 70%, not significantly different from histology.
      Major post-RFA morbidity was 8%. No mortality, Child deterioration, patient
      withdrawal because of tumor progression was observed. Post-OLT 3-year
      patient/graft survival was 83%. CONCLUSIONS: RFA is a safe and effective
      treatment of small HCC in cirrhotics awaiting OLT, although tumor size (>3 cm)
      and time from treatment (>1 year) predict a high risk of tumor persistence in the
      targeted nodule. RFA should not be considered an independent therapy for HCC.

PMID- 15492575
TI  - Prevention of postsurgery-induced abdominal adhesions by electrospun
      bioabsorbable nanofibrous poly(lactide-co-glycolide)-based membranes.
AB  - OBJECTIVES: The objective of this study was to evaluate the efficacy of nonwoven
      bioabsorbable nanofibrous membranes of poly(lactideco-glycolide) for prevention
      of postsurgery-induced abdominal adhesions. SUMMARY BACKGROUND DATA: Recent
      reports indicated that current materials used for adhesion prevention have only
      limited success. Studies on other bioabsorbable materials using a new fabrication
      technique demonstrated the promising potential of generating an improved and
      inexpensive product that is suitable for a variety of surgical applications.
      METHODS: All rats underwent a midline celiotomy. The cecum was identified and
      scored using an abrasive pad until serosal bleeding was noted on the anterior
      surface. A 1 x 1 cm of abdominal wall muscle was excised directly over the cecal
      wound. The celiotomy was then closed in 2 layers immediately (control) after a
      barrier was laid in between the cecum and the abdominal wall. All rats underwent
      a second celiotomy after 28 days to evaluate the extent of abdominal adhesions
      qualitatively and quantitatively. RESULTS: Cecal adhesions were reduced from 78%
      in the control group to 50% in the group using biodegradable poly(lactide-co
      glycolide) (PLGA) nonwoven nanofibrous membranes (n = 10, P = 0.2) and to 22% in
      the group using membranes containing PLGA and poly(ethylene glycol)/poly(D,L
      lactide) (PEG-PLA) blends (n = 9, P = 0.03). Electrospinning method also enabled
      us to load an antibiotic drug Cefoxitin sodium (Mefoxin; Merck Inc., West Point,
      PA) with high efficacy. The electrospun PLGA/PEG-PLA membranes impregnated with 5
      wt% cefoxitin sodium, which amounts to approximately 10% of the systemic daily
      dose typically taken after surgery in humans, completely prevented cecal
      adhesions (0%) in rats. CONCLUSIONS: Electrospun nonwoven bioabsorbable
      nanofibrous membranes of poly(lactide-co-glycolide) were effective to reduce
      adhesions at the site of injury using an objective rat model. The membrane acted
      as a physical barrier but with drug-delivery capability. The combined advantages
      of composition adjustment, drug-loading capability, and easy placement handling
      (relatively hydrophobic) make these membranes potentially successful candidates
      for further clinical evaluations.

PMID- 15492576
TI  - Postoperative protein sparing with epidural analgesia and hypocaloric dextrose.
AB  - OBJECTIVE: We examined the hypothesis that epidural analgesia prevents the
      increase in amino acid oxidation after elective colorectal surgery in patients
      receiving hypocaloric infusion of dextrose. SUMMARY BACKGROUND DATA: Increased
      oxidative protein loss after surgery may adversely affect postoperative outcome.
      We have previously shown that effective segmental pain relief by epidural
      analgesia improves postoperative substrate utilization, resulting in less protein
      catabolism. METHODS: We randomly allocated 10 patients to receive general
      anesthesia combined with epidural analgesia using bupivacaine/fentanyl and 10 to
      receive general anesthesia followed by patient-controlled analgesia with
      intravenous morphine. All patients received a peripheral 72-hour infusion of
      dextrose 10% from the day before until the second day after surgery. The dextrose
      infusion rate was adjusted to provide 50% of the patients' resting energy
      expenditure. The primary end point was whole-body leucine oxidation as determined
      by a stable isotope tracer technique (l-[1-C]leucine). RESULTS: In the
      intravenous analgesia group, leucine oxidation increased from 19 +/- 4 to 28 +/-
      6 micromol kg h after surgery. Epidural analgesia prevented this increase of
      leucine oxidation (preoperative 21 +/- 6 micromol kg h, postoperative 21 +/- 5
      micromol kg h). This difference was statistically significant (P = 0.01; analysis
      of variance for repeated measures). CONCLUSION: Perioperative epidural analgesia
      and hypocaloric dextrose infusion suppress the postoperative increase in amino
      acid oxidation, thereby saving more than 100 g of lean body mass per day.

PMID- 15492578
TI  - Laparoscopic inguinal hernia repair complicates future pelvic oncologic surgery.

PMID- 15492579
TI  - Liver transplantation for hepatocellular carcinoma: need for a new patient
      selection strategy.

PMID- 15492581
TI  - Is primary resection and salvage transplantation for hepatocellular carcinoma a
      reasonable strategy?

PMID- 15492583
TI  - Coronary collateral channels--physiology and functional importance.

PMID- 15492584
TI  - Pathophysiology of collateral development.
AB  - The formation of collateral arteries in patients suffering from occlusive
      atherosclerotic vascular diseases has been frequently reported. The growth of
      these collateral arteries has been termed 'arteriogenesis'. Clinical observations
      and investigations using various animal models support the hypothesis that the
      mechanism of arteriogenesis is based on the remodelling of pre-existing
      collateral anastomoses. This process seems to be mainly triggered by fluid shear
      stress which is induced by the altered blood flow conditions after an arterial
      occlusion. Early arteriogenesis involves the activation of collateral endothelial
      cells, the attraction of leukocytes to the collateral vascular wall and
      subsequently their invasion into the perivascular space of the collateral vessel.
      In a second phase, proliferation of vascular cells is initiated by growth factors
      mainly released from accumulated leukocytes. Furthermore, tissue degradation and
      changes in the extracellular matrix are observed. Unravelling the mechanisms of
      arteriogenesis is crucial to the development of successful therapeutic approaches
      for the treatment of patients with ischemic vascular diseases.

PMID- 15492585
TI  - Collateral vessel physiology and functional impact-in vivo assessment of
      collateral channels.
AB  - The existence and recruitment of collateral vessels within the coronary
      circulation may account for the tremendous variability in presentation, symptoms
      and outcome in patients with coronary atherosclerosis. Multiple episodes of
      ischemia have been found to produce the stimuli necessary for the growth of new
      vessels which result in collateral blood flow. Furthermore, there is also a
      subset of patients with readily recruitable collateral vessels that function to
      limit myocardial necrosis during an acute ischemic event. Promising early studies
      have utilized angiogenic growth factors as a means to stimulate collateral
      growth, bringing a renewal interest in their assessment and significance. We
      review, in brief, the significance and understanding of the development of
      coronary collaterals as well as the available means to assess them.

PMID- 15492586
TI  - Collateral vessel physiology and functional impact- experimental evidence of
      collateral behaviour.
AB  - The clinical variable predicting the development of collateral arteries in humans
      is the hemodynamic severity of coronary stenoses. Hyperemia induces an overall
      increase in coronary collateral flow in patients with coronary artery disease
      (CAD). There is a reduction in hyperemia-induced myocardial perfusion in the
      collateral-dependent vascular area in about 10% of patients with CAD and superior
      collateral vessels (collateral steal). Collateral recruitment has a major impact
      in the equation: ischemic tolerance=preconditioning+collateral recruitment.

PMID- 15492587
TI  - Clinical contribution of the collateral circulation to myocardial protection.
AB  - This section describes the clinical evidence for benefit from coronary collateral
      channels. There is data to suggest the presence of a protective effect in
      patients sustaining myocardial infarction regardless of whether they receive
      reperfusion therapy, and whether the collaterals were preformed. The role of pre
      infarction angina in stimulating collateral development remains a contentious
      issue.

PMID- 15492588
TI  - Therapeutic manipulation of the collateral circulation--future directions.
AB  - Stimulation of collateral artery growth is an attractive alternative treatment
      modality for patients with coronary or peripheral artery disease. Decades of
      basic research have led to a reasonable understanding of the mechanisms behind
      collateral artery growth although 'bench research' is still absolutely warranted
      for better understanding. It is some 7 years ago that the first clinical trials
      on therapeutic manipulation of the collateral circulation were published and this
      field is still relatively new and in large parts unexplored. Arteriogenesis,
      namely the growth of large collateral conductance arteries, seems to be the best
      biological substrate candidate for therapeutic manipulation. Future studies in
      this field will have to cope with problems of substance choice, clinical
      detection methods and unwanted side-effects.

PMID- 15492589
TI  - Do collaterals affect heart rate variability in patients with acute myocardial
      infarction?
AB  - BACKGROUND: The protective effects and the prognostic importance of collaterals
      during and after acute myocardial infarction (MI) are under debate and heart rate
      variability (HRV) is a strong predictor of risk of mortality and arrhythmic
      events after acute MI. We aimed to examine the effects of collateral circulation
      on HRV in the early period after acute MI. METHODS: Sixty-four patients admitted
      to our clinics who were diagnosed with acute anterior MI and underwent
      thrombolytic therapy were enrolled in this study. We applied 24 h Holter
      monitoring for HRV analysis to all patients and compared the patients with and
      without collaterals to the infarct-related artery. RESULTS: Mean heart rate, low
      frequency (LF) (day, night and 24 h) and LF/high frequency (HF) (day, night and
      24 h) were higher, SD of all NN intervals (SDNN), root mean square of successive
      differences (RMSSD), number of NN intervals that differed by more than 50 ms from
      the adjacent interval divided by the total number of all NN intervals (PNN50) and
      HF night values were lower in patients without collaterals than in those with
      collaterals. SDNN was negatively correlated with left anterior descending
      coronary artery (LAD) stenosis, ventricle score indices and left ventricular
      ejection fraction (LVEF); LF/HF ratio was positively correlated with ventricle
      score indices and negatively correlated with LVEF and Thrombolysis in Myocardial
      Infarction flow grade. Linear regression analysis showed that ventricle score
      index and coronary collaterals affect HRV and LAD stenosis, ventricle score, LVEF
      and coronary collaterals affect LF/HF ratio. A SDNN <80 ms increased the
      development of ventricular arrhythmias in the early period by 4.7 fold, a LF/HF
      ratio >2.7 increased it by 9.8 fold and a LVEF <35% increased it by 12.8 fold,
      whereas the presence of well-developed collaterals decreased the arrhythmia
      development by 2.5 fold. CONCLUSIONS: The collaterals to the infarct-related
      artery have great impact on HRV, autonomic nervous system activity and the
      development of ventricular arrhythmias in patients with acute anterior MI. Our
      results suggest a protective role of collaterals on myocardial electrophysiology
      in the early period after acute MI.

PMID- 15492590
TI  - Poor coronary collateral circulation is associated with higher concentrations of
      soluble adhesion molecules in patients with single-vessel disease.
AB  - OBJECTIVE: As the endothelium and inflammatory cells play a crucial role in the
      development of collaterals after a sudden or slowly progressing stenosis of
      coronary arteries, the levels of soluble endothelial adhesion molecules (CAMs)
      including vascular cell adhesion molecule (VCAM-1) intercellular adhesion
      molecule-1 (ICAM-1) and E-selectin were compared between patients with poor
      coronary collaterals and patients with well-developed collaterals. METHODS: In
      the study, 97 non-diabetic subjects with single-vessel disease were included.
      Collateral supply to the stenotic coronary artery was determined by angiographic
      grading system of 0-3 (Rentrop et al. J Am Coll Cardiol 1985; 5:587-592). Serum
      levels of adhesion molecules were measured by enzyme-linked immunosorbent assay.
      RESULTS: Patients were divided into two groups according to the collateral degree
      (group A: 50 patients with grade 0 and 1; group B: 47 patients with grade 2 and 3
      collaterals). The groups were well matched with respect to baseline clinical and
      angiographic characteristics. Levels of soluble VCAM-1 (mean+/-SEM; 875+/-26.6
      versus 742.7+/-35.1 ng/ml; P=0.004), ICAM-1 (322.4+/-12.4 versus 269.4+/-13.3
      ng/ml; P=0.005), and E-selectin (43.6+/-2.6 versus 33+/-2.4 ng/ml; P=0.004) were
      found to be significantly higher in group A in comparison with group B. In
      addition, when patients were divided into four groups according to the collateral
      degree, patients with grade 0 collaterals had the highest values and those with
      grade 3 collaterals had the lowest values for all these molecules. CONCLUSIONS:
      We concluded that poor collateral circulation is associated with increased levels
      of soluble CAMs in patients with obstructive coronary artery disease. However,
      further studies are needed to elucidate the exact role of these inflammatory
      markers in the setting of poor collateral circulation.

PMID- 15492591
TI  - Novel insights into coronary lumen preservation during progression of coronary
      atherosclerosis in coronary atherosclerosis-prone rabbits.
AB  - BACKGROUND: In coronary atherosclerosis-prone Watanabe heritable hyperlipidaemic
      (WHHLCA) rabbits, an animal model for low-density lipoprotein receptor deficiency
      and spontaneous coronary atherosclerosis, the coronary arteries show compensatory
      remodelling during the progression of atherosclerosis. Therefore, we analysed
      coronary remodelling of WHHLCA rabbits quantitatively using a method that
      eliminates the limitations of previous analytical methods. METHODS: Arterial
      remodelling was evaluated in perfusion-fixed coronary arteries of 11 WHHLCA
      rabbits using both new and previous analyses. With the improved methods removing
      limitations on quantitative analysis of arterial remodelling, we evaluated how
      lumen area or arterial size changed with accumulating atherosclerotic plaques
      compared to before plaque development. The original lumen area before plaque
      development was calculated using the diameter-length relationship. Wall shear
      stress change ratio was calculated from changes in arterial size. RESULTS: Using
      the old analytical method (and as seen in similar human studies), lumen area
      increased up to a level of 29% of cross-sectional narrowing. However, with the
      improved analysis, in cross-sectioning narrowing at levels below 10%, the lumen
      area modestly decreased, and when the cross-sectional narrowing ranged from 10
      68%, the lumen area remained constant, and diminished sharply despite continued
      remodelling when cross-sectional narrowing reached 70% or above. Arterial
      remodelling progressed quantitatively to a slight increase in arterial wall shear
      stress as well as lumen area up to a level of 70% cross-sectional narrowing.
      CONCLUSIONS: These findings demonstrate marked influences of arterial tapering
      and individual variation of arterial size on quantitative analysis of arterial
      remodelling, and provide the novel insight that coronary compensatory remodelling
      in atherosclerosis maintains the lumen size up to levels of 70% cross-sectional
      narrowing in proportion to wall shear stress.

PMID- 15492592
TI  - Integration of clinical and imaging data to predict the presence of coronary
      artery disease with the use of neural networks.
AB  - AIM: To establish proof of the principle that a computer-based neural network
      method can be employed that will enhance diagnostic accuracy vis-a-vis image
      analysis alone in the interpretation of treadmill exercise tests performed in
      conjunction with myocardial perfusion imaging. MATERIALS AND METHODS: One-hundred
      and-two patients underwent myocardial perfusion imaging in association with the
      standard Bruce protocol. Twenty objective parameters describing each patient's
      exercise physiology, general clinical status and image appearance were used to
      train an artificial neural network. Classification accuracy of the neural network
      and clinical interpretation was determined by coronary angiography. We evaluated
      the ability of the neural network to integrate clinical, exercise and imaging
      data to determine the likelihood of coronary artery disease and compared these
      results with an optimized method of clinical image interpretation, which made use
      of all available clinical, angiographic and stress test data. RESULTS: The
      artificial neural network had a sensitivity of 88% and a specificity of 65% for
      detection of ischemic heart disease and was comparable to that of the optimized
      clinical method (sensitivity 80%, specificity 69%). Incorporation of clinical and
      exercise data significantly improved the predictive accuracy of the network
      compared to a network based on image data alone (P<0.05). CONCLUSION: The results
      show a computer-based neural network can perform as well as expert readers
      working under optimal conditions including full knowledge of the patient's
      clinical, prior angiographic and stress test data. Thus, the method is promising
      as a diagnostic aid to the recognition of ischemic heart disease in the clinical
      setting of treadmill exercise testing in conjunction with myocardial perfusion
      imaging.

PMID- 15492593
TI  - Cutting balloon angioplasty is superior to balloon angioplasty or stent
      implantation for small coronary artery disease.
AB  - The aim of this study is to demonstrate initial results and long-term outcomes of
      patients after receiving cutting balloon angioplasty (CBA), balloon angioplasty
      (BA), or stenting for small vessel diseases. We studied a total of 327 lesions of
      small coronary disease treated either by CBA (n=87), BA (n=130), or stenting
      (n=110) in two affiliated institutes. A small coronary artery was defined as a
      reference vessel <2.5 mm using quantitative coronary angiography (QCA).
      Angiographic restenosis was encountered in 31% of the CBA, 46.5% of the BA, and
      43.9% of the stent (p=0.048). Major adverse cardiac events (death, myocardial
      infarction, and target lesion revascularization) at follow-up were significantly
      lower in the CBA compared to other groups (CBA, 20.3%; BA, 37.3%; stent, 33.3%;
      p=0.036). The CBA procedure provided superior angiographic and clinical outcomes
      to the stenting or BA. The CBA may be a cost-effective and reasonable approach
      for the treatment of lesions in small coronary diseases.

PMID- 15492594
TI  - Only transient increase of vascular growth factors and microvascular density
      after percutaneous myocardial laser.
AB  - OBJECTIVE: We tested the hypothesis that percutaneous myocardial laser may
      stimulate microvascular growth in areas surrounding the laser channels. METHODS:
      We conducted a study of 24 domestic pigs, which underwent percutaneous myocardial
      laser to left ventricular myocardium using holmium:YAG laser. The pigs were
      sacrificed in groups of four after one day, 3-4 days, one week, three weeks and
      six weeks. Frozen sections from both normal and treated myocardium were prepared
      for immunofluorescence microscopy and stained with antibodies against von
      Willebrand factor, vascular endothelial growth factor (VEGF) and Extra Domain-A
      cellular fibronectin (ED-AcFN). Microvascular density (MVD) and vascular area
      (VA) were determined in sections stained with antibodies against von Willebrand
      factor VIII using a digitised image analysis system. When determined in laser
      treated areas, channel core remnants were excluded from analysis. RESULTS: Within
      the laser channel remnants and in the tissue closely surrounding these,
      expression of VEGF and ED-AcFN increased significantly after treatment at one, 3
      4, and seven days and decreased to normal at three and six weeks. Expression of
      ED-AcFN was detected adjacent to endothelial cells of microvessels. The original
      laser channels were rapidly invaded by granulation tissue. There was no sign of
      recanalization at any stage during the six weeks. Morphometric analysis showed no
      increase in MVD and VA in the myocardium surrounding the laser channels.
      CONCLUSION: An increase of VEGF and ED-AcFN after myocardial laser is transient
      and is not associated with increase of MVD or VA in myocardium not involving
      laser channel remnants.

PMID- 15492596
TI  - Bibliography. Current world literature.

PMID- 15492595
TI  - Remifentanil limits infarct size but attenuates preconditioning-induced infarct
      limitation.
AB  - OBJECTIVES: We investigated the influence of the narcotic anesthetic remifentanil
      on irreversible myocardial ischemic injury. METHODS: New Zealand White rabbits
      were anesthetized with propofol (0.7-1.8 mg.kg.min) and then subjected to 30 min
      regional myocardial ischemia and 3 h reperfusion (CON). Some animals also
      underwent ischemic preconditioning, elicited by either one (IP1) or two (IP2)
      cycles of 5 min ischemia and 5 min reperfusion, and/or remifentanil, administered
      either as a transient infusion mimicking the preconditioning protocol (RP2, 10
      microg x kg x min) or as a continuous infusion (R, 3-10 microg x kg x min).
      Rabbits were randomly assigned to experimental groups. Infarct size was assessed
      with tetrazolium. Results are reported as mean+/-SD. RESULTS: Non-preconditioned
      infarct size was approximately 50% of the area-at-risk (49.6+/-20.1% CON). Both
      one and two cycles of ischemic preconditioning markedly reduced infarct size
      (49.6+/-20.1% CON versus 18.6+/-8.6% IP and versus 7.5+/-7.6% IP2; both p<0.001).
      Preconditioning with remifentanil modestly reduced infarct size (49.6+/-20.1% CON
      versus 29.3+/-8.5% RP2; p<0.01). However, sustained administration of
      remifentanil did not provide protection (49.6+/-20.1% CON versus 43.9+/-16.2% R),
      and it attenuated the protection offered by preconditioning (49.6+/-20.1% CON
      versus 35.6+/-20.7% R+IP1, p=NS; and versus 14.5+/-14.5% R+IP2; p<0.05).
      CONCLUSION: Transient pre-ischemic administration of remifentanil modestly
      reduces infarct size in propofol-anesthetized rabbits, but continuous
      administration of remifentanil increases the threshold for ischemic
      preconditioning-induced infarct limitation.

PMID- 15492597
TI  - Magnetic resonance cholangiopancreatography: is it becoming the study of choice
      for evaluating obstructive jaundice?

PMID- 15492598
TI  - The role of leptin in NAFLD: contender or pretender?

PMID- 15492599
TI  - Vitamin supplementation: what the gastroenterologist needs to know.
AB  - BACKGROUND: The vitamin business is a multimillion dollar industry. Aggressive
      marketing strategies are used to make claims for the health benefits of these
      products. Observational studies suggest that people who consume vitamin
      supplements decrease their risks for cancer, cardiovascular disease, and
      gastrointestinal disease. What is the evidence for these claims, and as a
      prescribing gastroenterologist, is there a scientific basis for vitamin
      supplementation? METHODS: A narrative review focusing on randomized controlled
      trials, where available, plus observational studies obtained from personal files,
      "on-line" searches, and references in reviewed articles. RESULTS: From the
      perspective of a gastroenterologist, there is strong evidence to recommend B12
      supplementation in gastric and intestinal disease, as well as pernicious anemia.
      There exists moderate evidence to support B12 supplements in pancreatic disease.
      Vitamin D and calcium supplementation are recommended for persons with disorders
      of malabsorption, cholestasis, and illnesses requiring chronic steroids. Only
      observational studies suggest a correlation between vitamin D/calcium and
      decreased colorectal adenoma recurrence. Although folic acid supplementation is
      beneficial in persons on medications such as methotrexate and sulfasalazine,
      studies are contradictory with regard to folic acid and colon cancer prevention.
      Overall, antioxidants have not been proven to decrease the risk for colorectal
      adenoma, gastric cancer, or esophageal cancer. CONCLUSIONS: Observational studies
      do not correlate with randomized clinical trials; therefore, few definitive
      recommendations can be made. Vitamin supplements are appropriate for recognized
      deficiencies; however, there is a lack of evidence to support their effects in
      the prevention of chronic disease.

PMID- 15492600
TI  - Pneumatic dilation for the treatment of achalasia in untreated patients and
      patients with failed Heller myotomy.
AB  - BACKGROUND: Laparoscopic Heller myotomy (HM) has become an increasingly preferred
      modality to treat achalasia. However, the treatment course after a failed myotomy
      is controversial with fears that pneumatic dilation (PD) has high perforation
      risk. GOAL: To compare success and safety of graded PD with Rigiflex balloons in
      achalasia patients without a prior HM (untreated cases) and those with a failed
      HM. STUDY: A total of 108 patients were retrospectively evaluated: 96 untreated
      cases (53 male, 43 female, mean age 51 years) and 12 failed HM(7 male, 5 female,
      mean age 54 years). Symptoms (dysphagia and regurgitation) and physiologic
      studies, lower esophageal sphincter pressure (LESP) and timed barium swallow,
      assessed pre- and post-PD. Success was defined as: 1) symptom improvement to </=2
      to 4 times per week, and 2) >/=80% decrease in 5-minute barium column height from
      initial timed barium swallow. RESULTS: A total of 139 PDs performed (117
      untreated cases, 22 failed HM): 2 perforations in untreated cases and none in
      failed HM group. Baseline demographics were similar, but failed HM patients had
      significantly lower LESP and timed barium swallow columns. Despite less LES
      resistance, failed HM group (symptom and physiologic success: 50% and 10%) did
      not do as well after PD as compared with untreated cases (symptom and physiologic
      success: 74% and 52%, respectively). Five failed HM patients had good symptom
      relief after PD compared with poor responders these patients were older (>50
      years) and had LESP >17 mm Hg. CONCLUSIONS: PD perforation risk is not higher
      after HM. Despite lower LES pressure, patients undergoing PD after failed HM do
      not do as well as untreated cases. Factors predicting better outcome include
      older age and higher LES pressure.

PMID- 15492601
TI  - A randomized controlled trial of gastric lavage prior to endoscopy for acute
      upper gastrointestinal bleeding.
AB  - GOALS: We hypothesized that large volume gastric lavage prior to endoscopy for
      acute upper gastrointestinal bleeding would improve the quality of endoscopic
      examination. BACKGROUND: Blood retained in the stomach can impair visualization
      during esophagogastroduodenoscopy. Patients with acute upper gastrointestinal
      bleeding and a retained gastric fundic pool during endoscopy may have worse
      outcomes than patients without a retained fundic pool. No trials to date have
      evaluated if large volume gastric lavage prior to endoscopy improves
      visualization during acute upper gastrointestinal bleeding. STUDY METHODS:
      Patients with acute upper gastrointestinal bleeding were randomized to
      esophagogastroduodenoscopy alone or large volume tap water gastric lavage prior
      to esophagogastroduodenoscopy. The quality of endoscopic visualization was
      assessed using a 5-point scale. Clinical outcomes were compared for lavaged and
      nonlavaged patients. RESULTS: A total of 39 patients were randomized. In 1
      patient, lavage was unsuccessful. The quality of visualization was not
      significantly different between groups for the esophagus, gastric antrum, or
      duodenum but was significantly better for the gastric fundus for patients
      randomized to lavage (P = 0.02). There was no significant difference between
      groups for ability to define a bleeding source, achieve hemostasis, recurrent
      bleeding, need for repeat endoscopy, and length of stay or death. There were no
      complications. CONCLUSIONS: Large volume gastric lavage prior to
      esophagogastroduodenoscopy for acute upper gastrointestinal bleeding is safe and
      provides better visualization of the gastric fundus.

PMID- 15492602
TI  - Symptoms, gastric function, and psychosocial factors in functional dyspepsia.
AB  - INTRODUCTION: The classification of functional dyspepsia into meaningful
      subgroups remains an important goal. The aim of this investigation was to
      determine correlations between dyspeptic symptoms with gastric physiology and
      psychologic distress. METHODS: Consecutive patients with functional dyspepsia
      were evaluated with electrogastrography (EGG), drink test, and solid phase
      gastric emptying. Subjects also completed the Nepean Dyspepsia Index, Psychologic
      General Well-Being Index, SCL-90R, and SF-36. RESULTS: Eighty-one patients were
      evaluated. Gastric emptying was performed in 29 of 81 patients and was abnormal
      in 21%, but no correlation existed between symptoms and T1/2 or TLAG. EGG was
      abnormal in 42% and drink test was abnormal in 40% of patients. Both were
      significantly associated with nausea but not with other symptoms. Significant
      correlations existed with 10 of 15 assessed symptoms and various subscales of the
      SCL-90R. Somatization was associated with abdominal burning, chest pain,
      abdominal pressure, abdominal discomfort, bad breath, chest burning, excessive
      fullness, bloating, abdominal pain, and regurgitation. Anxiety was associated
      with abdominal burning, chest pain, abdominal pressure, and abdominal discomfort.
      Anger-hostility was associated with abdominal burning and abdominal pressure.
      Increased interpersonal sensitivity was associated with abdominal burning and
      chest burning. SCL-90R Global Symptom Score was associated with abdominal
      burning, chest pain, abdominal discomfort, and bad breath. CONCLUSIONS: Abnormal
      gastric physiology as measured in this study was not associated with symptoms
      other than nausea. Significant associations existed between measures of
      psychiatric distress and digestive symptoms. Symptoms in functional dyspepsia had
      greater associations with psychologic distress than with commonly employed tests
      of gastric physiology.

PMID- 15492603
TI  - Phytobezoars and trichobezoars: a 10-year experience.
AB  - INTRODUCTION: Bezoars are retained concretions of animal or vegetable material in
      the gastrointestinal tract. Most bezoars reside in the stomach, but they may be
      encountered elsewhere. Previous gastric surgery, which has resulted in impaired
      gastric emptying and/or decreased acid production, is usually the cause of
      bezoars. Phytobezoars are more common, while trichobezoars are rare. Endoscopy
      and gastrografin swallow may aid in diagnosis. The treatment of bezoars can be
      either conservative or surgical. METHODS: After searching the computerized
      medical database, all files of hospitalized patients in the years 1992 to 2002
      with the diagnoses "bezoars," "phytobezoars," and "tricobezoars" were evaluated.
      RESULTS: Eighteen patients had bezoars: 16 had phytobezoars and 2 patients were
      diagnosed as having trichobezoars. Eleven of the patients had previous gastric
      operation. All patients but one were treated surgically. Two unusual cases of
      trichobezoar are presented here. DISCUSSION: Thorough understanding of bezoars
      can allow the clinician to be especially alert when dealing with those patients
      most likely to develop them, and thus diagnose the condition at an early stage.

PMID- 15492604
TI  - Clinical evolution of celiac disease in Italy 1982-2002.
AB  - GOALS: The aim of this work is to assess how the clinical features of celiac
      disease have changed in Italy after the widespread introduction of serologic
      tests in 1993. STUDY: Twenty Italian Clinical Centers collected information from
      1982 until 2002 on 1968 patients older than 18 years diagnosed with celiac
      disease. RESULTS: The results show that the incidence of atypical and silent
      cases of celiac disease has increased after the wider availability of serological
      test, which has allowed earlier diagnosis and treatment. CONCLUSIONS: This paper
      provides a view on the evolution of the clinical features of celiac disease in
      Italy over 2 decades. The relevance of the analysis is supported by the fact that
      Italy is one of the countries with the highest incidence of celiac disease. These
      findings underline the importance of a timely diagnosis of celiac disease.

PMID- 15492605
TI  - Diarrhea in medical care workers with severe acute respiratory syndrome.
AB  - BACKGROUND AND GOAL: Several known coronavirus species cause a variety of
      diseases, including respiratory or enteric diseases. The purpose of this study
      was to investigate the interesting enteric symptoms of the medical care workers
      who were evidently infected with SARS by means of respiratory transmission.
      STUDY: Between May 1 and June 16, 2003, we enrolled 16 medical care workers who
      fulfilled the definition of probable SARS. Samples used for the detection of
      coronavirus RNA by RT-PCR were collected from throat and rectal swabs during
      acute phase. Serum anti-SARS IgG was checked by enzyme-linked immunosorbent
      assays at the convalescent phase. RESULTS: The incidence of watery diarrhea was
      18.8% (3 of 16). The RT-PCR of coronavirus was positive in three (18.8%) of 16
      throat swabs and in none (0%) of seven rectal swabs. Serum anti-coronavirus IgG
      was positive in 13 of the 15 patients (86.7%). The mortality rate was 6.25% (1 of
      16). The diarrhea rate in our hospital was significantly lower in comparison with
      the 73% (55 of 75) of the Amoy Gardens outbreak in Hong Kong (P = 0.000073), and
      similar to the 19.6% (27 of 138) of the hospital-acquired outbreak in the Prince
      of Wales Hospital in Hong Kong (P = 0.798). In contrast to the high positive rate
      of feces RT-PCR (97%) in Amoy Gardens, our positive rate in rectal swab RT-PCT
      (0%) was significantly lower (P = 0.00000002). CONCLUSIONS: Hospital-acquired
      SARS cases infected mainly by respiratory route less commonly presented with
      diarrhea. Lower intestinal viral load, when the virus spread by respiratory
      route, may be contributive to lower diarrhea rate and lower positive rate in
      rectal swab RT-PCR.

PMID- 15492606
TI  - Eosinophilic gastroenteritis associated with systemic lupus erythematosus.
AB  - Eosinophilic gastroenteritis is an uncommon disease with an obscure etiology,
      although associations with allergy, the idiopathic hypereosinophilic syndrome,
      and connective tissue disease have been reported. We present the case of a 37
      year-old woman with a history of idiopathic thrombocytopenic purpura who
      presented with refractory nausea, vomiting, and abdominal pain. Imaging studies
      were significant for bowel wall thickening and ascites, while laboratory studies
      revealed a positive antinuclear antibody (ANA), a positive anti-double stranded
      (DS) DNA antibody, low complement, and proteinuria. Exploratory laparotomy with
      gastric and small bowel biopsies established the diagnosis of eosinophilic
      gastroenteritis. In addition, the patient met clinical criteria for the diagnosis
      of systemic lupus erythematosus. Previous studies have described eosinophilic
      gastroenteritis in patients with scleroderma, polymyositis, or dermatomyositis.
      This is the first report to our knowledge of an individual with eosinophilic
      gastroenteritis and systemic lupus erythematosus.

PMID- 15492607
TI  - Magnetic resonance cholangiopancreatography in obstructive jaundice.
AB  - GOALS: To determine the ability of magnetic resonance cholangiopancreatography
      (MRCP) to diagnose the level and cause of obstruction in patients with
      obstructive jaundice. BACKGROUND: The limitations of available imaging modalities
      have led to the increasing use of MRCP, which is a noninvasive and highly
      accurate technique in evaluating patients with biliary obstruction. STUDY: Thirty
      patients were included in this study. MRCP was done using a fat suppressed,
      heavily T2 weighted fast spin echo sequence. The MRCP findings were confirmed on
      surgical exploration or clinical follow-up. RESULTS: MRCP could correctly
      identify ductal dilatation and the level of obstruction in all cases, except one.
      All causes of obstruction, except three, were detected. It failed to detect a
      common bile duct calculus in a minimally dilated ductal system and misdiagnosed a
      case of focal chronic pancreatitis as carcinoma head pancreas and a small
      pancreatic head mass as cholangiocarcinoma. It had a sensitivity of 94.44%,
      specificity of 81.81%, positive predictive value of 89.47%, and negative
      predictive value of 90% for the detection of malignant causes. The overall
      diagnostic accuracy for detection of level and cause of obstruction was 96.3% and
      89.65%, respectively. CONCLUSION: The high diagnostic accuracy of MRCP in
      evaluating patients with obstructive jaundice indicates that it has the potential
      to become the diagnostic modality of choice in such patients.

PMID- 15492608
TI  - Relationship between unexplained elevations in alanine aminotransferase and serum
      leptin in U.S. adults: results from the Third National Health and Nutrition
      Examination Survey (NHANES III).
AB  - INTRODUCTION: There has been an interest to explore whether serum leptin plays
      any role in the pathogenesis of chronic liver disease. We conducted a case
      control study to evaluate the relationship between unexplained elevations in ALT
      and serum leptin in NHANES III participants. METHODS: A total of 6343 adults who
      had fasting serum leptin and ALT measured as part of NHANES III constituted our
      study group. From this database, we have constructed cohorts of patients with
      unexplained elevations in ALT according to published criteria and compared their
      serum leptin levels to matched controls without liver disease and matched
      controls with hepatitis C. Leptin was also compared between patients with
      unexplained elevations in ALT with and without metabolic syndrome. RESULTS: Serum
      leptin in 288 patients with unexplained elevations in ALT was 13.3 +/- 9.9 ng/mL
      and was not significantly different than 720 controls without liver disease (13.6
      +/- 11.9 ng/mL, P = 0.6). Serum leptin in another group of patients with
      unexplained elevations in ALT and hepatitis C controls was also not significantly
      different (8.0 +/- 4.8 vs. 8.8 +/- 7.4 ng/mL, respectively, P = 0.5). There was
      no independent relationship between the presence of metabolic syndrome and serum
      leptin in individuals with unexplained elevations in ALT (P = 0.8). CONCLUSIONS:
      Individuals with unexplained elevations in ALT did not have higher levels of
      serum leptin than the matched controls. As unexplained elevations in ALT may
      signify the presence of nonalcoholic fatty liver disease in NHANES III
      participants, our data provide indirect evidence against a role for serum leptin
      in the pathogenesis of nonalcoholic fatty liver disease.

PMID- 15492609
TI  - Prevalence and natural history of gastric antral vascular ectasia in patients
      undergoing orthotopic liver transplantation.
AB  - GOALS: To describe the prevalence and natural history of gastric antral vascular
      ectasia (GAVE) in patients with end-stage liver disease undergoing orthotopic
      liver transplantation (OLT). BACKGROUND: GAVE is a well-recognized cause of
      gastrointestinal hemorrhage. Although 30% of patients with GAVE have liver
      disease, the prevalence of GAVE in patients with cirrhosis is not known. STUDY:
      We reviewed clinical records of patients who underwent OLT at our institution
      from February 1, 1998 to June 2003. Demographic and clinical details were
      recorded with attention to findings during upper endoscopy before and after OLT.
      RESULTS: A total of 597 patients underwent OLT, and 345 were evaluated
      preoperatively with esophagogastroduodenoscopy (EGD). Eight (2.3%) were found to
      have GAVE before OLT. Three of these eight underwent EGD after OLT, and GAVE was
      absent in all three. None of the patients with GAVE experienced gastrointestinal
      bleeding postoperatively. CONCLUSIONS: GAVE was present in nearly 1 in 40
      patients with end-stage liver disease who underwent EGD before OLT at our
      institution and appears to resolve after transplant. These findings are
      consistent with a previous report documenting resolution of GAVE after OLT.

PMID- 15492610
TI  - Silent celiac disease in chronic hepatitis C: impact of interferon treatment on
      the disease onset and clinical outcome.
AB  - GOALS: To assess the impact of interferon treatment on celiac disease onset in
      hepatitis C patients and to clarify its clinical relevance and outcome.
      BACKGROUND: Hepatitis C is associated with autoimmunity, which can be exacerbated
      by interferon treatment. Cases of celiac disease activation during interferon
      treatment have been reported. STUDY: Retrospective evaluation of 534 hepatitis C
      patients with or without symptoms compatible with celiac disease onset during
      interferon treatment and 225 controls. Anti-transglutaminase antibodies were
      assayed. HLA-DQA1 and -B1 loci were typed. Upper gastrointestinal endoscopy was
      applied to confirm the diagnosis in antibody-positive patients. RESULTS: Anti
      transglutaminase antibodies were detected before treatment in 1.3% of hepatitis C
      patients and in 0.4% of controls (not significant). Eighty-six percent of
      patients with anti-transglutaminase antibodies showed activation of celiac
      disease while on interferon. Symptoms ranged from mild to severe, and interferon
      had to be discontinued in 2 of 7 (29%) patients. Symptoms disappeared in 6 of 7
      patients after interferon withdrawal. Onset of symptoms compatible with celiac
      disease during interferon therapy was significantly associated with the presence
      of anti-transglutaminase antibodies (OR 53). CONCLUSIONS: In hepatitis C
      patients, the activation of silent celiac disease during interferon treatment is
      almost universal and should be suspected, but it uncommonly requires interferon
      treatment discontinuation. Symptoms subside after interferon withdrawal.

PMID- 15492611
TI  - Rapid progression of autoimmune hepatitis in the background of primary sclerosing
      cholangitis.
AB  - "Overlap syndromes" have been reported among various autoimmune liver diseases,
      particularly between primary biliary cirrhosis and autoimmune hepatitis (AIH) in
      adults and between AIH and autoimmune cholangitis in children. The overlap
      syndrome of AIH and primary sclerosing cholangitis (PSC), however, has been
      scarcely reported. Furthermore, in most of the reported cases of AIH/PSC overlap
      syndrome, PSC and AIH were believed to occur simultaneously. We report a case of
      a 34-year-old woman who has ulcerative colitis and PSC (diagnosed by colonoscopy,
      histology, and cholangiogram) and 7 years later develops rapidly progressive
      liver failure and hemolytic anemia from AIH. Liver biopsy showed dense portal
      lymphoplasmacytic infiltrate with interface hepatitis and acidophil bodies
      confirming AIH. She responded well to immunosuppressive therapy with steroids,
      both with respect to her liver disease and her autoimmune hemolytic anemia.
      Additionally, her clinical symptoms of fatigue, jaundice, and pruritus improved
      markedly and quickly. Overlap or "crossover" syndrome should be considered in all
      patients with PSC when they present with sudden deterioration of the liver
      function and changes in liver enzymes. By making the diagnosis of AIH in a
      patient with well-established PSC, appropriate treatment can be initiated,
      resulting in the patient's prompt recovery.

PMID- 15492612
TI  - Sigmoid volvulus in three college-age teenagers.

PMID- 15492613
TI  - Diabetes mellitus responsive to corticosteroids in autoimmune pancreatitis.

PMID- 15492614
TI  - Ileal ulcers due to Aeromonas hydrophilia infection.

PMID- 15492615
TI  - Adrenal metastasis from hepatocellular carcinoma through an adrenohepatic fusion.

PMID- 15492616
TI  - Acute upper airway obstruction induced by an indwelling long intestinal tube:
      attention to the nasogastric tube syndrome.

PMID- 15492617
TI  - Successful endoscopic management of band erosion complicating gastric bypass
      surgery.

PMID- 15492618
TI  - Recurrent postpartum exacerbation of chronic ulcerative colitis.

PMID- 15492619
TI  - Surgical intervention for the ingestion of multiple magnets by children.

PMID- 15492620
TI  - Distinguishing features of nontraumatic and traumatic retinal dialyses.

PMID- 15492621
TI  - Risks of intravitreous injection: a comprehensive review.
AB  - PURPOSE: To evaluate the prevalence of the most common serious adverse events
      associated with intravitreous (IVT) injection. METHODS: A systematic search of
      the literature via PubMed from 1966 to March 1, 2004, was conducted to identify
      studies evaluating the safety of IVT injection. Data submitted in New Drug
      Applications to the U.S. Food and Drug Administration for drugs administered into
      the vitreous were included where available. Serious adverse events reported in
      each study were recorded, and risk per eye and risk per injection were calculated
      for the following serious adverse events: endophthalmitis, retinal detachment,
      iritis/uveitis, intraocular hemorrhage, ocular hypertension, cataract, and
      hypotony. Rare complications also were noted. RESULTS: Data from 14,866 IVT
      injections in 4,382 eyes were analyzed. There were 38 cases of endophthalmitis
      (including those reported as pseudoendophthalmitis) for a prevalence of 0.3% per
      injection and 0.9% per eye. Excluding cases reported specifically as
      pseudoendophthalmitis, the prevalence of endophthalmitis was 0.2% per injection
      and 0.5% per eye. Retinal detachment, iritis/uveitis, ocular hypertension,
      cataract, intraocular hemorrhage, and hypotony were generally associated with IVT
      injection of specific compounds and were infrequently attributed by the
      investigators to the injection procedure itself. Retinal vascular occlusions were
      described rarely in patients after IVT injection, and it was unclear in most
      cases whether these represented true injection-related complications or chance
      associations. CONCLUSION: The risk of serious adverse events reported after IVT
      injection is low. Nevertheless, careful attention to injection technique and
      appropriate postinjection monitoring are essential because uncommon injection
      related complications may be associated with permanent vision loss.

PMID- 15492622
TI  - Minimizing the risk of endophthalmitis following intravitreous injections.
AB  - PURPOSE: To review techniques that are important in preventing endophthalmitis
      following intravitreous injections based on the available evidence. METHODS: A
      review of the literature regarding existing evidence that is relevant to post
      injection endophthalmitis prophylaxis. RESULTS: The available evidence regarding
      endophthalmitis prophylaxis is largely based on intraocular surgery, particularly
      cataract surgery. Despite the controversy and the paucity of evidence regarding
      endophthalmitis prophylaxis for intravitreous injections, it is recommended that
      povidone-iodine should be used prior to intravitreous injections to minimize or
      eliminate the presence of ocular surface bacteria. Administration of topical
      antibiotics may also be considered before and after the intravitreous injections.
      Strict adherence to aseptic techniques, including the use of an eyelide speculum
      is also important. CONCLUSION: Endophthalmitic can occur following intravitreous
      injections. Prophylaxis with topical povidone-iodine, and possibly antibiotics,
      as well as adherence to aseptic technique may minimize the risk of post-injection
      endophthalmitis.

PMID- 15492623
TI  - Characteristics of sixty myopic eyes with pre-laser in situ keratomileusis
      retinal examination and post-laser in situ keratomileusis retinal lesions.
AB  - PURPOSE: A survey of eyes with pre-laser in situ keratomileusis (LASIK) retinal
      examinations and characteristics of post-LASIK retinal breaks and retinal
      detachments (RDs). METHODS: A survey of worldwide vitreoretinal surgeons (424
      physicians). Surveyed information included demographics, best-corrected visual
      acuity, degree of myopia, pre- and post-LASIK retinal findings, follow-up time,
      and treatment outcome. RESULTS: Sixty eyes with pre-LASIK retinal examinations
      developed post-LASIK retinal breaks and RDs. There was an average of 2.3 breaks
      per eye, yielding a total of 140 breaks in the 60 eyes. Forty eyes also had RDs
      besides the retinal breaks. Large percentages of eyes had substantial myopia
      (mean myopia, -9.5 +/- 5.8 diopters [D]) and complex vitreoretinal complications.
      Forty percent developed vitreoretinal complications within 6 months after LASIK.
      The 20 eyes that developed more extensive RDs (>3 clock hours) had a
      significantly higher mean myopia than did the 6 eyes that developed limited RD (<
      or = 3 clock hours) within 12 months after LASIK (-8.92 +/- 6.82 D versus -3.50
      +/- 1.97 D, P = 0.03). There were significant statistical differences in
      distribution of retinal breaks and tears between the temporal and nasal quadrants
      (P < 0.001, P < 0.001, respectively, chi2, but not between the superior and
      inferior quadrants. CONCLUSION: Distributions of retinal breaks in this study
      were comparable with results found in non-LASIK eyes in young myopes. Treatment
      for post-LASIK vitreoretinal complications was highly successful. The
      vulnerability of such highly myopic eyes for vitreoretinal complications warrants
      their close monitoring.

PMID- 15492624
TI  - Characteristics and outcomes of choroidal neovascularization occurring after
      macular hole surgery.
AB  - PURPOSE: To study the characteristics and outcomes of choroidal
      neovascularization (CNV) developing after surgery for idiopathic macular holes.
      METHODS: Retrospective, noncomparative case series. Search of diagnostic and
      procedure databases of four participating institutes identified nine eyes of
      eight patients with CNV after surgery for idiopathic macular hole. Demographic,
      clinical, and fundus fluorescein angiographic data were abstracted from patients'
      medical records. RESULTS: Choroidal neovascularization developed 6 weeks to 30
      months after macular hole surgery. The macular hole was closed in all cases. The
      CNV complex involved the foveal region in 9 (100%) eyes, was predominantly
      classic in 8 (89%) eyes, and was associated with moderate to severe leakage of
      fluorescein in 8 (89%) eyes. The CNV was crescent-shaped and spared the central
      area of retinal pigment epithelial mottling that corresponded to the site of the
      macular hole in 6 (67%) cases. Other fluorescein angiographic features included
      retinal pigment epitheliopathy in 6 (67%) eyes and presence of drusen in 7 (78%)
      eyes. The final visual acuity after a mean follow-up period of 11.2 months
      (range, 3-16 months) was 20/50 to 20/80 in 2 (22%) eyes, 20/100 to 20/200 in 1
      (11%) eye, and less than 20/200 in 6 (67%) eyes. CONCLUSION: Choroidal
      neovascular complexes occurring after macular hole surgery tend to share certain
      characteristics, including foveal involvement, frequent sparing of the central
      area corresponding to the site of the closed macular hole, and generally poor
      visual outcomes. Therapeutic modalities including photodynamic therapy and
      surgical options may be considered in these patients.

PMID- 15492625
TI  - Vitreous surgery with and without internal limiting membrane peeling for macular
      hole repair.
AB  - PURPOSE: To compare surgical results for idiopathic macular holes with and
      without internal limiting membrane (ILM) peeling in a series of consecutive
      patients during an 8-year period. METHODS: A retrospective, nonrandomized,
      comparative trial. Four hundred seventeen eyes with macular holes without ILM
      peeling were compared with 175 eyes with ILM peeling. All eyes underwent pars
      plana vitrectomy with intravitreous gas, followed by head-down positioning. No
      adjunctive therapies were used. Comparison of closure and reopening rates and
      visual acuity with and without ILM peeling was analyzed. RESULTS: Initial success
      rate significantly improved from 81% to 92% with ILM peeling. ILM peeling
      significantly improved the initial success rates in all categories of
      preoperative features. Reopening rates significantly decreased from 7% to 0.6%
      with ILM peeling. Among successful cases, line improvement was 6.0 in ILM
      reserved eyes and 5.8 in ILM-peeled eyes. Among all cases, line improvement was
      5.4 in ILM-reserved eyes and 5.7 in ILM-peeled eyes. Initial success rate of
      holes measuring more than 400 microm was significantly less than that of holes
      measuring less than 400 microm with or without ILM peeling. Initial success rate
      of holes older than 6 months old was significantly less than that for holes less
      than 6 months old without ILM peeling. CONCLUSIONS: Internal limiting membrane
      peeling shows high closure and low reopening rates in macular hole surgery. ILM
      peeling is beneficial in older holes but is limited in larger holes. ILM peeling
      does not significantly improve visual acuity.

PMID- 15492626
TI  - Surgery for epimacular membrane: impact of retinal internal limiting membrane
      removal on functional outcome.
AB  - PURPOSE: To examine eyes that underwent vitrectomy and peeling of epimacular
      membrane and to correlate the functional results with the presence or absence of
      an internal limiting membrane (ILM) in the histologic specimens. METHODS: Seventy
      one eyes underwent vitrectomy and peeling of an epimacular membrane. These
      membranes were examined with a transmission electron microscope. Best-corrected
      visual acuities were recorded before macular surgery, 1 month after surgery, and
      at the final examination and were compared between group 1 (ILM removed) and
      group 2 (ILM not removed). The age, gender, status of the lens preoperatively,
      type of epimacular membrane (idiopathic or secondary), intraoperative and
      postoperative complications, and elapsed time between vitrectomy and cataract
      operation were recorded. All 71 eyes were pseudophakic at the final examination.
      The mean follow-up was 21 months. RESULTS: Long segments of ILM were found in the
      specimens from 55 (77%) of the cases. Final visual acuities were better in group
      1 (ILM removed) than in group 2 (ILM not removed, P = 0.004). The visual gain was
      3.1 lines on the Early Treatment of Diabetic Retinopathy Study chart in group 1
      and 0.9 lines in group 2. At the last examination, a recurrent epimacular
      membrane was observed in 5 (9%) eyes of group 1 and 9 (56%) eyes of group 2.
      CONCLUSION: ILM removal during surgery for epimacular membrane is associated with
      better final vision and a lower risk of recurrent epimacular membrane.

PMID- 15492627
TI  - Trypan blue-assisted vitrectomy.
AB  - PURPOSE: To evaluate the efficacy of trypan blue dye for the staining and removal
      of the internal limiting membrane, epiretinal membranes, and the posterior
      hyaloid during pars plana vitrectomy. METHODS: The authors retrospectively
      reviewed a consecutive series of 26 eyes of 26 patients in whom trypan blue 0.15%
      dye was used to stain intraocular tissues during vitrectomy surgery. RESULTS: The
      cases reviewed included the following diagnoses: epiretinal membrane (13),
      macular hole (9), proliferative vitreoretinopathy (2), chronic pseudophakic
      cystoid macular edema (1), and chronic diabetic macular edema (1). The
      application of trypan blue resulted in a useful and consistent bluish staining,
      facilitating the identification, delineation, and removal of the epiretinal
      membrane, internal limiting membrane, or posterior hyaloid in all patients. Six
      months after the surgery, visual acuity was better or the same in 21 of the 26
      patients. There were no clinical signs of retinal toxicity in any patients.
      CONCLUSION: Trypan blue staining of the internal limiting membrane, epiretinal
      membranes, and the posterior hyaloid is a useful adjunct in vitreoretinal surgery
      and improves the efficiency and safety of membrane identification and removal.

PMID- 15492628
TI  - Surgical removal of peripapillary choroidal neovascularization associated with
      optic nerve drusen.
AB  - PURPOSE: To assess the anatomical and functional results after surgical removal
      of peripapillary choroidal neovascularization (CNV) associated with optic nerve
      head drusen. METHODS: A retrospective study was carried out on four eyes (four
      patients) undergoing vitrectomy, retinotomy, and removal of CNV associated with
      optic disk drusen. CNV was preoperatively demonstrated by fluorescein angiography
      in all cases. In three cases, the CNV had a subfoveal extension, and a serous
      hemorrhagic retinal detachment was the cause of the central vision disturbance in
      the remaining one. Optic nerve head drusen were bilateral and were confirmed with
      computed tomography scan. RESULTS: Visual acuity (VA) improved in all cases after
      a follow-up ranging from 12 to 42 months. Preoperative VA was 20/200, 20/200,
      20/50, and count fingers and final VA was 20/50, 20/25, 20/25, and 20/30,
      respectively. There was no evidence of CNV recurrence during the follow-up
      period. CONCLUSION: The results of surgical removal of peripapillary CNV with
      macular involvement associated with optic nerve head drusen are very encouraging,
      especially if we consider the variable outcome of the natural course in these
      cases.

PMID- 15492629
TI  - Risk factors for retention of subretinal perfluorocarbon liquid in vitreoretinal
      surgery.
AB  - PURPOSE: To analyze factors that may lead to inadvertent subretinal retention of
      perfluorocarbon liquid (PFCL) after vitreoretinal surgery and compare surgical
      outcomes and complications associated with these events. DESIGN: Consecutive
      retrospective study. METHODS: The authors retrospectively reviewed the charts of
      72 vitreoretinal surgeries using intraoperative PFCL and its removal through
      fluid-air exchange and subsequent tamponade. Indications for surgery included
      trauma, retinal detachment, giant retinal tear, and submacular hemorrhage. Most
      interventions studied had significant amounts of proliferative vitreoretinopathy
      and were required after failed or complicated previous vitreoretinal surgery.
      MAIN OUTCOME MEASURES: Analysis was focused on the occurrence of subretinal
      retention of PFCL during different surgical procedures and techniques,
      indications, anatomic and visual results, and complications. RESULTS: At the last
      follow-up, the retina was completely attached in 97% of eyes treated with PFCL
      after 1 or 2 vitrectomies. Subretinal PFCL was found in 8 (11.1%) eyes. There was
      no statistical difference in the retention rate for perfluorodecalin and
      perfluoro-n-octane. The factor most significantly associated with subretinal
      retention of PFCL was the presence and large size of a peripheral retinotomy. All
      cases of subretinal PFCL had a retinotomy of 120 degrees or larger. The average
      retinotomy size in these cases was 259 degrees . Subretinal PFCL was found in 40%
      of eyes with a 360 degrees retinotomy. Small and medium-sized retinal breaks were
      not associated with PFCL retention. Another surgical procedure that correlated
      significantly with subretinal PFCL was lack of saline rinse during fluid-air
      exchange. Only 1 of the 23 eyes that were rinsed had subretinal PFCL, although
      many had large retinotomies. CONCLUSION: Subretinal PFCL retention is most likely
      to occur in eyes with large peripheral retinotomies, especially if 360 degrees .
      Saline rinse seems to be useful in the prevention of subretinal PFCL. The
      presence of subretinal PFCL does not seem to affect visual and anatomic success
      when located outside the macula, at least during an intermediate period of follow
      up.

PMID- 15492630
TI  - Comparison of retinal outcomes after scleral buckle or lens-sparing vitrectomy
      for stage 4 retinopathy of prematurity.
AB  - PURPOSE: To compare anatomic outcomes after lens-sparing vitrectomy (LSV) or
      scleral buckle (SB) for stage 4 retinopathy of prematurity (ROP). METHODS:
      Nonrandomized, retrospective study of infants consecutively treated for stage 4
      ROP by LSV or SB. Outcomes were retinal attachment at 1 month of initial surgery
      and at the end of follow-up (6 months) and number of procedures to achieve
      retinal attachment. Exact chi2 methods determined significance, and student's t
      test compared mean postmenstrual age and birthweight between the groups. RESULTS:
      After one procedure, LSV (72%) was associated with retinal attachment more often
      than was SB (31%). At the end of follow-up, after one or more procedures, there
      was no difference in retinal reattachment rate between LSV or SB as the first
      procedure. There were no differences between the surgical groups by mean
      postmenstrual age and birthweight or severity of ROP determined by zone, clock
      hours of ridge elevation, or quadrants of plus disease. CONCLUSION: This study
      supports the hypothesis that vitrectomy by LSV stops progressive stage 4 ROP. As
      an initial procedure, LSV was associated with retinal attachment more often than
      SB. Future prospective studies can determine the effects of LSV and SB on visual
      development in progressive stage 4 ROP.

PMID- 15492631
TI  - Serous macular detachment secondary to distant retinal vascular disorders.
AB  - PURPOSE: To report tomographic features of macular edema associated with distant
      retinal vascular disorders. METHODS: Six eyes with macular edema (three with
      extramacular branch retinal vein occlusion and three with Coats disease)
      underwent fluorescein angiography to detect dye leakage and optical coherence
      tomography to evaluate the macular features and measure the foveal height
      (distance between inner retinal surface and retinal pigment epithelium) and the
      retinal thickness (thickness of neurosensory retina) at the central fovea.
      RESULTS: Fluorescein angiography showed widespread nonperfusion and retinal vein
      staining in the eyes with a branch retinal vein occlusion not involving the
      macula. In eyes with Coats disease, nonperfused areas, telangiectatic retinal
      vessels, and aneurysms were seen in the peripheral fundus on fluorescein
      angiography. In one eye with Coats disease, telangiectatic vessels and aneurysms
      were seen in the nasal mid periphery of the optic disk. There was no dye leakage
      in the macular area in any eyes. Optical coherence tomography showed subretinal
      fluid and retinal swelling at the fovea in all eyes. The foveal height ranged
      from 300 to 697 microm (mean, 478 microm) and retinal thicknesses ranged from 170
      to 280 microm (mean, 233 microm). CONCLUSION: Distant retinal vascular leakage
      causes serous retinal detachment in the macula. The macula is predisposed to
      collect subretinal fluid although retinal vascular leakage is far from the
      macula.

PMID- 15492632
TI  - Outcome of choroidal neovascularization in angioid streaks after photodynamic
      therapy.
AB  - PURPOSE: To evaluate the visual and anatomic outcomes of photodynamic therapy for
      choroidal neovascularization (CNV) in patients with angioid streaks. METHODS: The
      authors retrospectively evaluated 40 consecutive patients (48 eyes) with visual
      acuity of 20/200 or greater who were treated at 6 referral centers for CNV
      associated with angioid streaks. Main outcome measures were visual acuity,
      greatest linear diameter of the lesion, and, in patients with nonsubfoveal CNV,
      distance from the foveola. RESULTS: Of 34 eyes with subfoveal CNV, 21 were
      followed up for at least 12 months (range, 5-33 months). Median visual acuity was
      20/50 at baseline and 20/120 at the final examination. The 12-month estimate of
      the percentage of eyes with vision loss of fewer than 3 lines was 68% (95%
      confidence interval, 50%-85%) by using survival analysis, whereas eyes with no
      increase in the greatest linear diameter were 45% (95% confidence interval, 27%
      62%). Fourteen eyes had extrafoveal (n = 11) or juxtafoveal (n = 3) CNV, 12 of
      which were followed up for at least 10 months (range, 4-36 months). Visual acuity
      was 20/40 or greater in all eyes with extrafoveal lesions at baseline and in 5 of
      12 eyes at the last examination, when 3 cases of CNV had become subfoveal. At
      baseline, visual acuity was low in two eyes with juxtafoveal CNV and nearly
      normal in the third. It remained substantially stable at the end of follow-up
      (range, 10-36 months), when two lesions were subfoveal. CONCLUSIONS: Most of our
      patients had good baseline visual function and, thus, were at high risk for
      losing vision because of the poor prognosis of CNV in angioid streaks. Because
      most had no or limited vision loss after 1 year, the authors suggest that
      photodynamic therapy can be used to try to limit or delay visual damage caused by
      this aggressive disease.

PMID- 15492633
TI  - Annular macular neuroretinopathy and multifocal electroretinographic and optical
      coherence tomographic findings.

PMID- 15492634
TI  - Retinal function after subconjunctival injection of carboplatin in fibrin
      sealant.
AB  - PURPOSE: To evaluate retinal function in a rabbit model after subconjunctival
      delivery of carboplatin in balanced saline solution (BSS) or fibrin sealant to
      determine possible retinal toxicity. METHODS: One group of rabbits (n = 5)
      received a unilateral subconjunctival injection of 12.2 +/- 1.0 mg/mL of
      carboplatin (Paraplatin) in BSS. Another group of rabbits (n = 5) received 25.1
      +/- 7.7 mg/mL of carboplatin in fibrin sealant (Hemaseel APR). Rabbits injected
      with fibrin sealant only (n = 2) and BSS only (n = 2) were used as control
      groups. Electroretinographic recordings consisted of a series of intensities
      presented under dark- and light-adapted conditions. Electroretinograms were
      recorded before the injection (baseline) and 2 days, 1, 2, and 3 weeks after the
      injection. After 3 weeks, all rabbit eyes were obtained for histopathologic
      examination. RESULTS: Transient reductions in the dark-adapted b-wave amplitudes
      were noted 2 days after treatment for eyes injected with carboplatin compared
      with the vehicle-only treatment groups. Other treatment groups and postinjection
      time points showed no significant changes from baseline. Retinal structure and
      thickness were normal 3 weeks after treatment for all treatment groups.
      CONCLUSION: Subconjunctival delivery of carboplatin in fibrin sealant or BSS does
      not have a toxic effect on retinal function or structure in a non-tumor-bearing
      rabbit model at the doses used in this study at 3 weeks' follow-up.

PMID- 15492635
TI  - The effect of prinomastat (AG3340), a potent inhibitor of matrix
      metalloproteinase, on a new animal model of epiretinal membrane.
AB  - PURPOSE: To develop a simple epiretinal membrane (ERM) animal model and evaluate
      the efficacy of prinomastat (AG3340), a synthetic inhibitor of matrix
      metalloproteinase. METHODS: This experiment was carried out on 18 eyes of nine
      Brown Norway rats. Preretinal hemorrhage was induced bilaterally using diode
      laser focused deeply on choroidal blood vessels. One day later, AG3340 was
      injected intravitreally in the right eyes while the left eyes received equal
      amounts of vehicle. The developed epiretinal membrane was measured in disk areas
      and compared between groups. RESULTS: Clinically, preretinal hemorrhage showed a
      slow clearance persisting for 8 to 10 weeks. ERM was well established around 12
      weeks. Histologically, ERMs consist of fibroblast and glial cells embedded in
      collagen-rich extracellular matrix infiltrated by macrophages. Seventy-five
      percent of the hemorrhagic laser burns in the control group developed ERM,
      whereas only 25% of the hemorrhagic laser burns in treated group developed ERM (P
      = 0.01). The total surface area of developed ERM was 3.66 DD in treated eyes
      versus 25.45 DD in control eyes (P = 0.049). The mean surface area of ERM per eye
      was 0.52 disk areas +/- 1.05 in treated eyes versus 3.18 +/- 3.07 in control
      eyes. CONCLUSION: We demonstrated that ERM can be induced on rat retina by simple
      hemorrhagic retinal laser coagulation. This new animal model could be used for
      future evaluation of different medical treatment modalities for proliferating
      ERM. Furthermore, AG3340 demonstrated an inhibitory effect on ERM formation in
      this new rat model.

PMID- 15492636
TI  - Diagnostic and therapeutic challenges.

PMID- 15492637
TI  - Indocyanine green angiographic findings in a case of acute annular outer
      retinopathy.

PMID- 15492638
TI  - Best dystrophy in a patient with an ocular histoplasmosis phenotype.

PMID- 15492639
TI  - Two cases of choroidal neovascularization treated with transpupillary
      thermotherapy in angioid streaks.

PMID- 15492640
TI  - Simple and stable technique of vitreous tap.

PMID- 15492641
TI  - Persistent afterimages (palinopsia) and photophobia in a patient with a history
      of LSD use.

PMID- 15492642
TI  - Retinal pigment epithelial tear associated with a serous retinal detachment in a
      patient with thrombotic thrombocytopenic purpura and hypertension.

PMID- 15492643
TI  - Endophthalmitis after intravitreal injection of frozen preprepared tissue
      plasminogen activator (tPA) for pneumatic displacement of submacular hemorrhage.

PMID- 15492644
TI  - Unsealed sclerotomy after intravitreal injection with a 30-gauge needle.

PMID- 15492645
TI  - Femtosecond laser-induced premacular hemorrhage.

PMID- 15492646
TI  - Appearance of brown areas after resolution of the acute phase of multiple
      evanescent white dot syndrome.

PMID- 15492647
TI  - A newly designed guarded radial optic neurotomy knife.

PMID- 15492649
TI  - A novel endolaparoscopic intragastric partitioning for treatment of morbid
      obesity.
AB  - Morbid obesity is a burgeoning health crisis. Significant morbidity is associated
      with the current gastric bypass, and, therefore, alternative surgical modalities
      are desired. A novel minimally invasive surgical technique, endoluminal gastric
      partitioning, is presented. Ten mongrel dogs underwent endolaparoscopic placement
      of intragastric mesh. Each circular prosthesis (Surgisis or prolene mesh) was 8
      cm in diameter with a 1.5 cm central aperture. The mesh was passed transorally
      into the gastric lumen and secured with a laparoscopic, intragastric suturing
      resulting in a 30 to 50 mL proximal gastric reservoir. The operation was
      successfully completed in all 10 animals. Nine of 10 animals were healthy at the
      scheduled sacrifice date. In 2 dogs, the intragastric mesh was 100% adherent to
      the gastric mucosa after 7 days. Four of the final 5 dogs demonstrated some
      degree of mucosal adherence after 1 week. Endoluminal placement of intragastric
      mesh appears feasible and safe. Long-term studies are necessary to demonstrate
      the efficacy and long-term weight loss of this, or alternate intraluminal gastric
      partitioning techniques.

PMID- 15492650
TI  - Effect of intra-abdominal pressure level on gastric intramucosal pH during
      pneumoperitoneum.
AB  - The present study was designed to examine the effect of intra-abdominal pressure
      level on gastric intramucosal pH using gastric tonometry during pneumoperitoneum.
      One hundred patients were prospectively randomized into 5 equal groups (N = 20
      each). Intra-abdominal pressure levels were 8, 10, 12, 14, and 16 mm Hg in groups
      I, II, III, IV, and V, respectively. Intramucosal pH measurement was done 2
      times: 30 minutes following insufflation and 1 hour after the ending of the
      surgery. In the first and second measurements, intramucosal pH values were found
      as 7.39 +/- 0.02 and 7.36 +/- 0.03 in group I; 7.41 +/- 0.03 and 7.38 +/- 0.03 in
      group II; 7.37 +/- 0.03 and 7.37 +/- 0.03 in group III; 7.36 +/- 0.03 and 7.37 +/
      0.03 in group IV; and 7.39 +/- 0.03, 7.36 +/- 0.03 in group V, respectively.
      Statistical significance was not found in the comparison of these values within
      the groups and between the groups (P > 0.005, for each). In conclusion, intra
      abdominal pressure between 8 and 16 mm Hg did not cause significant difference in
      gastric intramucosal pH.

PMID- 15492651
TI  - Prevalence and risk factors for gallstone disease.
AB  - Gallstone disease is a main public health problem. The overall prevalence data
      range from 3.9% in the pre-echographic era to 13.7% when ultrasonography was used
      as a diagnostic tool. This study is aimed to determine the prevalence of
      gallstone disease in a medium income level population in Lima, as well as the
      relationship with some risk factors: age, sex, familiar history and obesity. A
      total of 534 adult men and women from a medium economic level underwent
      ultrasonographic examination of abdomen for detection of gallstone disease (July
      2003). The echographic evaluation was performed by 10 general surgeons trained in
      ultrasonography. Likewise, 4 risk factors--age, gender, familial history, and
      obesity--were analyzed. Pearson chi2 test (2-sided) was used with a probability
      of <0.05 for statistical significance and logistic regression analyses for
      assessment of confounding factors. The prevalence founded was 15%. Eighty-one of
      534 participants had lithiasis. Compared to the age group under 30, the odds
      ratio for the 31 to 50 years and >50 years of age group was 0.9 and 1.1,
      respectively. The female-male ratio was 1.07 and the odds ratio 0.8. The
      prevalence of gallstone disease in people reporting a first-degree relative with
      lithiasis was 21%, whereas in participants without such a condition, it was 13%.
      On the other hand, a familial history was present in 38% of the lithiasis group
      and in 25% of the nonlithiasis group. The odds ratio for familial history was 1.8
      (P = 0.01, 95% confidence interval 1.1-2.9). The prevalence of the disease for
      body mass index <24, 25 to 29, and higher than 30 was 17%, 14% and 13%,
      respectively. Compared to the reference group (body mass index <24), the other 2
      groups (body mass index 25-29 and >30) both had a similar odds ratio, 0.8.
      Logistic regression analyses showed an odds ratio of 1.9 for familiar history
      (95% confidence interval 1.1-3.2), whereas the odds ratio of the overweight (body
      mass index 25-29) and obese group (body mass index >30) when compared to the
      normal group, BMI <24, was 0.7 and 0.9, respectively. The prevalence data for
      gallstone disease remain slightly higher than those previously reported. Although
      the familiar history was the only characteristic with a statistically significant
      positive relationship with lithiasis, additional studies are needed because few
      biases could not be completely avoided and some confounding factors were not
      controlled.

PMID- 15492652
TI  - Computed tomography scanning and recurrence after laparoscopic ventral hernia
      repair.
AB  - Laparoscopic ventral hernia repair is an advancing surgical method. It seems to
      have fewer recurrences than open surgery. However, with patients suspected of
      recurrence after laparoscopic hernia repair, it can be very difficult to
      determine whether or not there is recurrence by clinical examination alone. The
      purpose of this article is to show that computed tomography is a valuable
      diagnostic tool in excluding recurrence after laparoscopic ventral hernia repair.
      A total of 35 patients were included in a prospective study. They underwent
      laparoscopic ventral hernia repair, and all patients suspected of recurrence were
      computed tomography scanned. Four patients were suspected of recurrence. They all
      presented symptoms of swelling or pain or both. The computed tomography scanning
      did not show the presence of recurrence in any of the 4 cases. Computed
      tomography scanning can provide exact information about the content of swelling
      and whether there is recurrence or not. We conclude that computed tomography
      scanning is suitable as a valid imaging method in doubtful cases considering
      ventral hernia recurrence after laparoscopic ventral hernia repair.

PMID- 15492653
TI  - Impact of previous appendectomy on the outcomes of endoscopic totally
      extraperitoneal inguinal hernioplasty.
AB  - Previous lower abdominal surgery presents a technical challenge during endoscopic
      totally extraperitoneal inguinal hernioplasty. Whether the presence of
      appendectomy scarring and adhesions will adversely influence the outcomes of
      totally extraperitoneal inguinal hernioplasty remains largely unknown. The
      objectives of the present study were to evaluate the safety of totally
      extraperitoneal inguinal hernioplasty in patients with a history of appendectomy
      and examine its impact on the perioperative outcomes. Between November 1999 and
      September 2003, patients who underwent totally extraperitoneal inguinal
      hernioplasty and had previous appendectomy were recruited as the appendectomy
      group. For each case patient, 3 age-matched cohorts were randomly selected during
      the same period. Perioperative data and postoperative outcomes were compared
      between the 2 groups of patients. A total of 92 patients, 23 cases and 69
      controls, were recruited. There was no predominance of either direct or indirect
      inguinal hernia in the appendectomy group. One patient in the appendectomy group
      required conversion to transabdominal preperitoneal inguinal hernioplasty because
      of adhesions. The incidence of peritoneal tear and operative time was higher and
      longer in the appendectomy group respectively but the differences were not
      significant. Comparisons of the mean duration of hospitalization, postoperative
      morbidity rates, pain scores, and time taken to resume normal activities showed
      no significant difference between the 2 groups. Totally extraperitoneal inguinal
      hernioplasty in patients who had previous appendectomy was technically safe. A
      higher incidence of peritoneal tear was anticipated in the presence of
      appendectomy scarring and adhesions. Postoperative recovery and outcomes were
      equivalent to those who had no history of appendectomy.

PMID- 15492654
TI  - Proper arrangement of the lines and cables in the setup of the laparoscopic
      surgery: development of new device "Line-Hanger".
AB  - Recently, with the rapid progress and introduction of new machineries and
      instruments for endoscopic surgery, the connecting lines and cables connecting
      machineries around the operating field are becoming more and more complicated.
      The lines and cables are often very troublesome, especially when the operator and
      assistant change their positions, and sometimes they are not only annoying but
      also potentially dangerous during the operative procedure. We feel there is a
      pressing need to develop a device to regulate the lines and cables. We developed
      a device for regulating the lines and cables in cooperation with Olympus Optical
      Co, Ltd (Tokyo, Japan) and named it "Line-Hanger." We have used it in more than
      30 cases of various kinds of endoscopic surgery. In this study, we compare the
      usefulness of the "Line-Hanger" with the conventional method: fixation of lines
      and cables to the drapes with Velcro(R). The girth of the operative personnel are
      freed from a jumble of cables, and they become ergonomically comfortable.
      Especially when operator and assistant are changing their position, it becomes
      very smooth. "Line-Hanger" is extremely useful for endoscopic surgery.

PMID- 15492655
TI  - Is umbilical flora responsible for wound infection after laparoscopic surgery?
AB  - To our knowledge, the association of umbilical flora and infections has not been
      studied yet. The aim of this study was to identify the causative agents for
      trocar site infections and to highlight whether there is association between
      umbilical flora and trocar site infections. One hundred consecutive patients who
      had undergone laparoscopic surgery were studied. Microbiological samples were
      taken from the umbilicus before (group 1) and after (group 2) antisepsis with
      povidone-iodine. Microbiological assessment was done for wounds suspected to be
      infected, and the wounds with positive cultures were classified as group 3. The
      incidence of wound infection was 8%. One hundred percent of the infections were
      associated with the extraction trocar. Eighty-nine percent of all of the
      infections occurred after laparoscopic cholecystectomy, whereas 11% occurred
      after laparoscopic appendectomy. The micro-organisms in group 3 did not belong to
      the skin flora, unlike the micro-organisms in groups 1 and 2, but hospital
      acquired pathogens were responsible for the infections. The umbilical flora and
      the bile are not the source of the surgical site infections after laparoscopic
      surgery in our study despite the considerations in the literature.

PMID- 15492656
TI  - Nonoperative management of iatrogenic lesions of celiac branches by using
      transcatheter arterial embolization.
AB  - We present our experience in the nonoperative management of iatrogenic lesions of
      celiac branches by using transcatheter arterial embolization. We treated 6
      pseudoaneurysms (5 intrahepatic and 1 of the gastroduodenal artery), 6 vessel
      lacerations (1 common hepatic artery, 1 right hepatic artery, 1 gastroduodenal
      artery, 2 pancreatoduodenal, 1 polar intrasplenic artery), 1 arterioportal
      fistula, and 1 arteriobiliary fistula; all the bleeding lesions were secondary to
      surgical, endoscopic, or interventional radiologic procedures.

PMID- 15492657
TI  - Laparoscopically guided distal ventriculoperitoneal shunt placement.
AB  - In standard techniques for performing ventriculoperitoneal shunts, the peritoneal
      catheter is threaded more or less blindly into the peritoneal cavity. Using
      laparoscopic techniques allows accurate peritoneal placement, without a large
      incision, even in replacement procedures and in patients with previous abdominal
      operations. We performed 28 laparoscopically guided ventriculoperitoneal shunt
      placements and shunt revisions in 24 patients with hydrocephalus (aged 6-80
      years). Sixteen of 24 patients (67%) had previous abdominal surgery. Laparoscopic
      shunt placement was successful in all patients. Mean operative time was 63 +/-
      34.9 minutes (range 15-150 minutes). In 2 patients, broken and disconnected
      distal parts of previously inserted shunts were removed from the abdomen. One
      shunt was removed following infection and other one was revised due to shunt
      malfunction. Three patients required revision of the cranial part of the shunt.
      Laparoscopically guided distal ventriculoperitoneal shunt placement provides
      definite patient benefits: it allows shunt placement under direct vision,
      associated with reduced trauma to the abdominal wall, and avoids a consequent
      risk of intra-abdominal adhesions.

PMID- 15492658
TI  - Endoclipping for gastric perforation after endoscopic polypectomy: an alternative
      treatment to avoid surgery.
AB  - A 47-year-old woman underwent endoscopic polypectomy of a villous adenoma in the
      lesser curvature of the gastric antrum. Shortly after the procedure, she
      complained of severe abdominal pain. An abdominal x-ray showed air under the
      diaphragm, suggestive of gastric perforation. On re-endoscopy, the cavity at the
      site of polypectomy was closed using endoscopically applied metallic clips. She
      was treated with intravenous hyperalimentation, omeprazole, and antibiotics for
      10 days. Ingestion of food was started 10 days after admission, and she was
      discharged without any complaints. She is free of symptoms on follow-up after 8
      months, and endoscopy showed complete healing of the perforation. The procedure
      is the third described for the stomach in the English literature and emphasizes
      the use of endoclipping in selected cases of small and well-defined perforations.

PMID- 15492659
TI  - Incidental cystadenoma after laparoscopic treatment of hepatic cysts: which
      strategy?
AB  - Biliary cystadenoma is a very rare hepatic neoplasm, accounting for fewer than 5%
      of cystic neoplasms of the liver; regardless of the various diagnostic
      modalities, such a lesion may be difficult to distinguish preoperatively from a
      cystadenocarcinoma. Although a diagnosis of cystadenoma during open hepatic
      surgery demands a complete surgical resection, there are few reports describing
      the correct approach to such lesions after a laparoscopic approach. This article
      presents the first case series of incidental cystadenoma after laparoscopic
      surgery for hepatic cystic lesions. One patient with a polycystic liver disease
      treated with a laparoscopic enucleation of the larger cyst declined the
      reintervention after the diagnosis of cystadenoma; she had no recurrence at
      follow-up. One patient with a large simple hepatic cyst laparoscopically
      enucleated had no recurrence at the 18-month follow-up. In one patient, there was
      a high suspicion of recurrence of cystadenoma after the laparoscopic fenestration
      of a large cyst, but a histopathological specimen obtained after the open
      surgical resection could not confirm any signs of cystadenoma. The incidental
      finding of biliary cystadenoma after laparoscopic fenestration of a cystic
      hepatic lesion requires an open hepatic resection. When a complete laparoscopic
      enucleation of the cyst may be assured, a strict clinical, biochemical, and
      radiologic follow-up could be considered as the definitive treatment, demanding
      the surgical intervention only in case of recurrence or high suspicion for
      malignancy.

PMID- 15492660
TI  - Laparoscopic correction of congenital portosystemic shunt in children.
AB  - Congenital portosystemic shunt is a rare clinical entity that may progress to
      jaundice, severe encephalopathy, and pulmonary hypertension and require surgical
      correction or coil embolization. We present a novel approach to the management of
      children with congenital portosystemic shunt by means of a minimally invasive
      surgical technique. Congenital portosystemic shunts were identified between the
      superior mesenteric vein and inferior vena cava in case 1 and between the splenic
      vein and left renal vein in case 2. Both of them were successfully ligated by
      laparoscopic approach, and catheters were subsequently replaced to monitor portal
      venous pressure. The patients tolerated the procedure well, and short-term
      results were excellent. Laparoscopic ligation of congenital portosystemic shunt
      is technically feasible and less invasive to the management of patients with
      congenital portosystemic shunts, preventing late onset, life-threatening
      complications.

PMID- 15492661
TI  - Laparoscopic splenectomy for splenic abscess.
AB  - Splenic abscess is a rare clinical entity, and splenectomy remains the treatment
      of choice. We sought to determine the safety and efficacy of laparoscopic
      splenectomy in this setting. Using a prospective database of laparoscopic
      splenectomy, we identified 4 patients who underwent surgery for splenic abscess
      (3 male, 1 female). Mean age was 55.5 (range 42-78) years. Patient symptoms
      included: fever and abdominal pain in 4 patients, pleural effusions in 2, and
      nausea and leukocytosis in 1. Risk factors for splenic abscess included septic
      emboli from bacterial endocarditis in 2 patients and acquired immune deficiency
      syndrome in 1. All patients underwent successful laparoscopic splenectomy. Mean
      operative time was 200 (range 160-220) minutes, and blood loss was 220 (range 100
      450) mL. There were no postoperative complications or deaths; postoperative
      length of stay averaged 14 (range 2-26) days. Despite the difficulty of the
      operation, the laparoscopic approach appears to be a safe and effective treatment
      of splenic abscess.

PMID- 15492662
TI  - Minimally invasive management of Crohn's disease complicated by ureteral
      stenosis.
AB  - Ureteral involvement due to Crohn's disease occurs in 3% to 6% of cases. Herein,
      we present a case of a 22-year-old woman with ileocolic Crohn's disease with
      right hydronephrosis due to compression of the ureter that was resolved with a 3
      stage, minimally invasive procedure (preoperative percutaneous nephrostomy,
      ureteral stent placement, and sequential laparoscopically assisted
      ileocolectomy). Percutaneous right nephrostomy drainage permitted us to prevent
      renal damage before surgery, and successive ureteral double-J catheter placement
      minimized the risk of ureteral damage during the laparoscopic procedure. The
      safety and feasibility of sequential minimally invasive management of ileocolonic
      Crohn's disease involving the right ureter was assessed, and a good cosmetic
      result was achieved.

PMID- 15492663
TI  - Rupture of rectal varices treated with endoscopic variceal ligation.
AB  - We report here 3 cases of rectal varices treated with endoscopic variceal
      ligation and discuss the pathogenesis, treatment, and prognosis of rectal varices
      with referring to previous reports. Of the 3 patients, 2 had been diagnosed as
      liver cirrhosis and 1 as extrahepatic portal hypertension. All of the 3 patients
      had previously undergone treatment of esophagogastric varices. The rupture of
      rectal varices appeared to have some relationship with the treatment of
      esophageal varices. In previous reports, 73% of patients with ruptured rectal
      varices treated with endoscopic injection sclerotherapy or endoscopic variceal
      ligation had undergone treatments of esophageal varices. The endoscopic
      treatments resulted in a favorable prognosis in 2 patients. Although no fatality
      from endoscopic injection sclerotherapy or endoscopic variceal ligation has been
      reported, 1 of the present 3 cases died of liver failure.

PMID- 15492664
TI  - A case of small spigelian hernias successfully treated by a simple laparoscopy
      assisted technique.
AB  - Clinical diagnosis and location of spigelian hernias is notoriously difficult,
      and the recommended repair techniques are many and varied. This report describes
      a case of ipsilateral double spigelian hernias treated by a laparoscopy-assisted
      technique hitherto undescribed. Suturing of the fascial defect was aided by a 14
      gauge angiocatheter that had traversed the full thickness of the abdominal wall
      firstly on one side of the hernial defect under laparoscopic guidance. A strong
      suture was threaded down the angiocatheter sheath. Its intra-abdominal end was
      made to traverse the other side of the defect and resurface upon withdrawal of a
      snare loop made of a folded suture inserted through the angiocatheter after the
      latter had been redirected to puncture the opposite edge. The knot was tied
      extracorporeally. This technique provides the benefits of laparoscopic
      localization to be combined with the advantages derived from the novel use of an
      angiocatheter--simplicity, low cost, safety, minimized tissue trauma, and
      improved cosmesis. It is therefore recommended for selected cases of small
      spigelian hernias.

PMID- 15492665
TI  - Gossypiboma: its laparoscopic diagnosis and removal.
AB  - Retained surgical sponges are an under-reported occurrence. Clinical presentation
      may be acute or subacute, and may follow months or even years after surgery. We
      report on a case in which laparoscopy was used to both diagnose and treat a
      retained surgical sponge.

PMID- 15492666
TI  - How to insert a double J stent in laparoscopic retroperitoneal dismembered
      pyeloplasty: a new technique.
AB  - Antegrade placement of double J stent during laparoscopic pyeloplasty is
      technically demanding and time consuming, especially when operating in the
      retroperitoneal space. We report a new, time-saving method to antegrade insertion
      of a double J stent that we use in retroperitoneal laparoscopic dismembered
      pyeloplasty. This technique employs the recovery of a guidewire introduced
      retrograde through an open tip ureteral catheter placed in the mid-ureter at the
      beginning of the procedure and brought into the sterile area. The guidewire
      issued through a laparoscopic port will be used in the antegrade insertion of the
      double J stent. We used this technique in 6 consecutive retroperitoneal
      laparoscopic dismembered pyeloplasties. The stent was correctly placed in all 6
      cases in less than 5 minutes without any difficulty. This is a simple and
      straightforward technique.

PMID- 15492675
TI  - Developing--and refining--a wound care plan.

PMID- 15492676
TI  - Leg ulcers in sickle cell disease.

PMID- 15492677
TI  - The epidermal skin barrier: implications for the wound care practitioner, part I.

PMID- 15492679
TI  - Obesity: impediment to postsurgical wound healing.
AB  - PURPOSE: To provide physicians and nurses with an overview of the impact of
      obesity on postoperative wound healing and how preplanning protocols can minimize
      skin and wound care problems in this patient population. TARGET AUDIENCE: This
      continuing education activity is intended for physicians and nurses with an
      interest in reducing skin and wound care problems in their patients who are
      obese. OBJECTIVES: After reading the article and taking the test, the participant
      will be able to: 1. Identify obesity-related changes in body systems and how
      these impede wound healing. 2. Identify complications of postoperative wound
      healing in obese patients and the assessments and intervention strategies that
      can reduce these complications. 3. Identify skin and wound care considerations
      for obese patients and the role of preplanning protocols in avoiding problems.

PMID- 15492681
TI  - Preplanning with protocols for skin and wound care in obese patients.
AB  - PURPOSE: To provide physicians and nurses with an overview of the impact of
      obesity on postoperative wound healing and how preplanning protocols can minimize
      skin and wound care problems in this patient population. TARGET AUDIENCE: This
      continuing education activity is intended for physicians and nurses with an
      interest in reducing skin and wound care problems in their patients who are
      obese. OBJECTIVES: After reading the article and taking the test, the participant
      will be able to: 1. Identify obesity-related changes in body systems and how
      these impede wound healing. 2. Identify complications of postoperative wound
      healing in obese patients and the assessments and intervention strategies that
      can reduce these complications. 3. Identify skin and wound care considerations
      for obese patients and the role of preplanning protocols in avoiding problems.

PMID- 15492683
TI  - Copayments impact hospital-owned outpatient wound departments.

PMID- 15492685
TI  - [A series on evidence-based medicine: objectives].

PMID- 15492686
TI  - [Randomised controlled trials: a readers' guide].

PMID- 15492687
TI  - [Meta-analysis: a readers' guide].

PMID- 15492688
TI  - [Study evaluating a diagnostic test: a readers' guide].

PMID- 15492689
TI  - [Scores and clinical evaluation].

PMID- 15492690
TI  - [Clinical prediction rules: a readers' guide].

PMID- 15492691
TI  - [Cost-effectiveness analysis: a readers' guide].

PMID- 15492692
TI  - [Clinical guidelines: a readers' guide].

PMID- 15492693
TI  - [Health-related quality of life measurement: a readers' guide].

PMID- 15492694
TI  - [Research questionnaire for beginners].

PMID- 15492695
TI  - [Demystifying decisional analysis].

PMID- 15492696
TI  - [Application of evidence based medicine to the individual patient: the role of
      decision analysis].

PMID- 15492715
TI  - [Multifocal motor neuropathy with persistent conduction blocks: 18 years on].
AB  - Multifocal motor neuropathy with persistent conduction blocks was firstly
      reported in 1986 and outlined from the group of purely motor diseases of the
      peripheral nervous system. The main criterion is the presence of conduction
      blocks located only on the motor nerves; additionally 30 percent of patients have
      IgM subclass serum antibodies directed against GM1 ganglioside. The clinical
      picture is a multifocal, asymmetrical, neuropathy, starting and predominant in
      the upper limbs, occurring in males aged 50 years and more, and having a
      progressive course. There is no biological sign besides elevated anti-GM1
      antibodies. CSF analysis discloses mild increased protein count. The course is
      unpredictable, the neuropathy may be strictly limited to one or two motor nerves,
      or spread to other motor nerves in the four limbs. There is no involvement of the
      sensory and the cranial nerves, no involvement of the autonomic and the central
      nervous system. The pathophysiology is unknown, animal models do not allow to
      confirm the role of humoral immunity, and the role of anti-GM1 antibodies is
      controversial. Randomized controlled trials have assessed the efficacy of
      intravenous immunoglobulins which dramatically improve strength in 70-80 percent
      of patients in the short term, but remain unable to prevent motor deterioration
      in most patients, together with the occurrence of new conduction blocks.
      Corticosteroids and plasma exchanges do not improve the patients and may be
      followed by transient worsening. Long-term efficacy of immunosuppressive agents
      is not known.

PMID- 15492716
TI  - [Frontal dysexecutive syndromes].
AB  - Investigation of executive functions is an approach which began with the early
      description of behavioral disorders induced by frontal damage. The development of
      neuropsychology has led to the description of a large variety of cognitive
      disorders. This type of approach has generated a large number of tests which are
      still used in clinical practice. More recently, theoretical approaches have
      proposed an organization of executive processes and have documented the diversity
      of executive functions and related anatomy. These studies have deeply influenced
      the clinical approach, the assessment and the diagnosis of executive disorders.
      For clinical practice, these data favor specific assessment of certain key
      behavioral and cognitive deficits investigated with a battery of tests.

PMID- 15492717
TI  - [Ataxic neuropathy associated with disialosylated antibodies: description of new
      clinical and biochemical forms].
AB  - INTRODUCTION: Polyneuropathies associated with IgM monoclonal gammopathy were
      recently recognized. Antibodies can react with glycoproteins such as myelin
      associated glycoprotein (MAG), or gangliosides containing one sialosyl epitope
      such as GM1 or several sialosyl epitopes (polysialyted gangliosides) including
      GD2, GD3, GT1b, GT1a, GQ1b. METHODS: We report on three patients presenting
      oculomotor dysfunction, chronic sensitive ataxic polyneuropathy, high
      sedimentation rate, IgM monoclonal paraprotein of unknown signification and
      antidisialosyl IgM antibodies and for two of them cold agglutinins. Such features
      have been previously described under the acronym "CANOMAD" (chronic ataxic
      neuropathy with ophthalmoplegia, M protein, agglutination and disialosyl
      antibodies). RESULTS: One of the patients presents extramembranous glomerulopathy
      and severe motor disability associated with this syndrome. The pathophysiology of
      the glomerulopathy seems to be linked with the polyneuropathy. Patients were
      treated either by intravenous immunoglobulin, corticosteroids or cyclophosphamid.
      Response to treatment differs in the three cases and there is currently no
      consensus. CONCLUSION: Our study demonstrates that spectrum of polyneuropathy
      associated with monoclonal polyneuropathy may be larger than originally
      described.

PMID- 15492718
TI  - [Prevalence of depression in multiple sclerosis: a review and meta-analysis].
AB  - INTRODUCTION: The aim of this paper was to review and summarize the data about
      the frequency of depression during multiple sclerosis (MS). MATERIAL AND METHODS:
      We performed a metaanalysis to combine the results of the studies which compared
      the frequency of depression in MS patients with the prevalence in patients with
      other chronic diseases. Eight controlled studies were identified via manual and
      computerized search of the Medline and PsychInfo databases. Given the various
      ways these studies reported their results, we used statistical procedures based
      on the combination of significance levels (the method of adding Zs and the method
      of adding ts). An additional statistical procedure, Cohen's d, was performed to
      estimate the effect of size. RESULTS: The two statistical methods yielded highly
      significant summary statistics: z=4.15 and z=3.98, respectively (p<0.0001). The
      effect of size (Cohen's d), which ranged from 0.02 to 0.70 with an average of
      0.29 (95 percent confidence interval: 0.09-0.49), can be considered as medium and
      hence clinically meaningful. CONCLUSION: These results suggest that the
      association between MS and depression is specific, that is not just casual nor
      due to the nonspecific factors inherent in every chronic disease.

PMID- 15492719
TI  - [NOEMIE: an epidemiological study of migraine at work: results from 17
      occupational health centres].
AB  - INTRODUCTION: A survey (NOEMIE, Nouvel Observatoire Epidemiologique de la
      Migraine en Entreprise) was carried out in France in 17 occupational healthcare
      units in order to identify subjects suffering from migraine headache with the aim
      of guiding them towards a healthcare program. The data collected in the
      participating units are presented. METHODS: and patients. NOEMIE was a national
      cross-sectional, observational, multicentric study with a 6-month follow-up. Two
      groups of migraine sufferers (according to IHS criteria) were included and
      divided into two groups: subjects already managed for their migraine (group A)
      and subjects who had not sought healthcare for migraine for more than 12 months
      (group B). The main objective was to evaluate changes in the quality-of-life
      score (QVM) 6 months later. RESULTS: At inclusion, the two groups were comparable
      for demographic features, history of migraine, and disease severity. A
      significant difference was observed between the two groups for frequency of
      attacks, disease management, and evaluation of treatment efficacy and of quality
      of-life. At 6 months, patient satisfaction and quality-of-life were significantly
      improved (6 to 10 point improvement). For the 4753 reported attacks, 12.4 percent
      of the patients in group A required sick leave versus 10.9 percent in group B.
      Frequency of sick leave was considerably improved in both groups. CONCLUSION: By
      identifying subjects suffering from migraine headache who had not sought specific
      medical care and advising them to seek medical management, the employee
      healthcare units improved the subjects' quality-of-life, promoted adequate
      medical management and reduced occupational consequences of migraine headache.

PMID- 15492720
TI  - [Neuro-Behcet's syndrome and thrombosis of Rosenthal's basilar vein: a report of
      twelve cases].
AB  - INTRODUCTION: Deep cerebral vein thrombosis is a specific clinical pattern of
      neuroBehcet. The clinical features of ischemic stroke by Rosenthal or internal
      cephalic vein thrombosis predominate. METHOD: A retrospective analysis of twelve
      cases of Rosenthal vein thrombosis revealing Behcet disease were analyzed. These
      cases accounted for one-quarter of the NeuroBehcet patients treated in our unit.
      RESULTS: The typical pattern of Rosenthal vein thrombosis clinical was present in
      all patients who developed a diencephalo-mesencephalic syndrome. CONCLUSION: The
      clinical presentation is highly suggestive of diagnosis confirmed by imaging.
      Outcome is favorable with corticosteroids and anticoagulation.

PMID- 15492721
TI  - [Pure subacute pandysautonomia: an assessment of treatment with intravenous
      polyvalent immunoglobulins].
AB  - INTRODUCTION: Acute or sub-acute pure dysautonomia is uncommon. We report a case
      of sub-acute pure pandysautonomia with favorable outcome after intravenous
      immunoglobulin therapy. CASE REPORT: A 29-year-old right-handed student, with an
      uneventful medical history presented, for one month, bilateral loss of visual
      acuity and digestive disorders, associating diarrhea, vomiting and anorexia.
      Physical examination revealed bilateral intrinsec oculomotor nerve palsy, a
      dryness syndrome and severe orthostatic hypotension. Ophthalmologic examination
      showed bilateral diffuse parasympathic impairment associating an Argyll Robertson
      pupil and full pupil light reflex abolition. Elevated protein level (0.93g/l) was
      the only cerebrospinal fluid anomaly. Serum tests were negative for anti
      gangliosides antibodies. The patient improved slowly after two series of
      intravenous immunoglobulin infusions. CONCLUSION: Clinical course and laboratory
      findings suggest that acute or sub-acute pure pandysautonomia events are likely
      to be related to acute polyradiculoneuritis. Therefore intravenous polyvalent
      immunoglobulin infusions should be attempted, even if their efficacy needs to be
      confirmed.

PMID- 15492722
TI  - [Flaccid tetraplegia following anti-tetanus vaccination].
AB  - INTRODUCTION: Anti-tetanus vaccination is considered to be very safe. However
      complications such as mononevritis, multinevritis or even polyradiculonevritis
      can be encountered. OBSERVATION: An 85-year-old man was admitted to our unit
      after a traffic accident caused by stroke. Seventy-two hours later the patient
      developed tetraplegia within a few hours, caused by neuropathy secondary to anti
      tetanus vaccination. DISCUSSION: In this elderly patient, the rapid onset and
      severe presentation of the tetraplegia as well as the past history of normal
      vaccination and the axonal form of the neuropathy could have led to a
      misdiagnosis of neuropathy after booster anti-tetanus vaccination. We first ruled
      out other possible diagnoses and then reviewed the possible mechanisms of
      neurological complications of vaccinations. These complications are probably
      underestimated in elderly hospitalized patients who receive a booster shot in the
      emergency department. CONCLUSION: This report illustrates the importance of
      reconsidering the benefit/risk relationship of anti-tetanos vaccination.

PMID- 15492723
TI  - [Intracranial haemorrhage associated with phaeochromocytoma].
AB  - INTRODUCTION: Pheochromocytoma is rarely disclosed by intracranial hemorrhage. We
      report two cases. OBSERVATION: The first 26-year-old patient developed
      subarachnoid hemorrhage due to a ruptured aneurysm of the middle cerebral artery.
      The second patient, aged 44 years, had a temporal hematoma. Diagnosis was
      suggested in both patients by hypertension and elevated urinary catecholamines
      and confirmed by imaging and MIBG scintigraphy. Adrenal gland tumors, on both
      glands in the first patient and on the right gland in the second were
      successfully removed; cranial hypertension totally regressed. Von Hippel Lindau
      disease was diagnosed by molecular genetics in the first patient. Paroxysmal
      hypertension could explain the brain hemorrhage in the first patient and may have
      favored aneurysmal rupture in the second. CONCLUSION: The relationships between
      pheochromocytoma and cerebral aneurysm are discussed.

PMID- 15492724
TI  - [Carcinomatous meningitis presenting with isolated headache].
AB  - INTRODUCTION: Carcinomatous meningitis reveals a solid cancer in 10 percent of
      cases. OBSERVATION: Our patient developed isolated headache which progressively
      worsened. Cranial Computerized Tomography (CT) was normal. Brain MRI showed
      multiples areas of contrast enhancements meningeal tissue associated with small
      nodulars deposits. Repeated cerebrospinal fluid (CSF) examinations revealed
      elevated tumor markers suspect cells. The diagnosis of pulmonary adenocarcinoma
      was established during systematic follow-up. CONCLUSION: The diagnosis of
      carcinomatous meningitis can be difficult to establish because of the non
      specific clinical presentation and the absence of suggestive context; negative
      CSF-cytology is frequent. MRI and elevated tumor markers in the CSF compared with
      the serum level contribute significantly to diagnosis.

PMID- 15492725
TI  - [Malignant non-Hodgkin lymphoma presenting with Garcin's syndrome].
AB  - INTRODUCTION: R Garcin described progressive unilateral cranial nerve palsy in
      1926. Garcin syndrome is characterized by progressive involvement of the cranial
      nerves culminating in total unilateral paralysis of all cranial nerves. Carcinoma
      of the skull base or ENT regions is the most common etiology. CASE REPORT: A 74
      year-old man developed signs involving the left Vth (V2 and V3) cranial nerve
      then the VIth, VIIth and VIIIth cranial nerves and finally the IXth and Xth. MRI
      showed involvement of these cranial nerves with gadolinium uptake and involvement
      of the pons at the terminal phase. Careful ENT explorations failed to reveal a
      cause. The lymphocyte count was elevated in the cerebrospinal fluid. The patient
      died one year after diagnosis and the general autopsy was normal. The
      neuropathological studies led to the post-mortem diagnosis of type B non-Hodgkin
      lymphoma. CONCLUSION: In patients with Garcin syndrome, lymphoma is a possible
      diagnosis when carcinoma of the ENT regions or of the skull bases are not
      present.

PMID- 15492726
TI  - [Facial palsy and central nervous system infection with varicella virus following
      adult chickenpox].
AB  - INTRODUCTION: VZV virus-related peripheral neuropathies usually occur after
      shingles in adults and more rarely after chickenpox in childhood. CASE REPORT: A
      54-year-old patient presented with a right VIIth nerve palsy following a
      chickenpox rash and recovered after antiviral treatment. CSF analysis revealed
      lymphocytic meningitis and the virus was identified by PCR. CONCLUSIONS: Although
      previous chickenpox was not found in the patient's past history, the probability
      of reinfection is likely. The virus can be assumed to affect the nervous system
      directly; the axonal or demyelinating mechanism of the neuropathy may be
      discussed.

PMID- 15492727
TI  - [Secondary focal dystonia].

PMID- 15492728
TI  - [Central dopaminergic receptors (Part II): pathophysiological and therapeutic
      considerations].
AB  - The five subtypes of dopaminergic receptors exhibit different transduction,
      cerebral localization, regulation, pharmacological, and physiological roles,
      explaining their multiple pathophysiological implications in different
      neuropsychiatric conditions which result, at least in part from anomalous
      dopaminergic neurotransmission: Parkinson's disease, schizophrenia, addiction,
      migraine, mode disorders, Gilles de la Tourette disease, hyperactivity syndrome
      with attention deficit. The wide range of pharmacological implications explains
      the diversity of the therapeutic approaches perspectives for development of new
      drugs for these neuropsychiatric conditions.

PMID- 15492729
TI  - Antiepileptic drugs in the 21st century.
AB  - During the past 10 years, there has been a welcome influx of novel agents for the
      treatment of epilepsy. Many show advantages compared to older agents, including
      better adverse effect profiles and lack of drug-drug interactions. The sheer
      number of agents now available makes distinction among them confusing at times.
      Agents differ in spectrum of action, pharmacokinetic profile (affecting dosing
      schedule and drug interactions), and titration time. This review highlights the
      differences between the various new agents and the more traditional antiseizure
      drugs. Evidence for the widespread use of these compounds outside their
      indication, particularly for diseases other than epilepsy, is reviewed as well.

PMID- 15492730
TI  - Reproductive dysfunction in women with epilepsy: antiepileptic drug effects on
      sex-steroid hormones.
AB  - Women with epilepsy are at risk for reproductive health dysfunction. Sex-steroid
      hormone abnormalities have been reported in women with epilepsy, but it has been
      difficult to determine whether these abnormalities are due to epilepsy-related
      hypothalamic-pituitary axis dysfunction, or to pharmacokinetic actions of
      antiepileptic drugs (AEDs). Sex-steroid hormones were evaluated in 84
      reproductive-aged women with epilepsy receiving an AED in monotherapy, and in 20
      nonepileptic controls. Estrone, free testosterone, and androstenedione were
      significantly lower in subjects receiving enzyme-inducing AEDs than in
      nonepileptic controls. Free testosterone was significantly elevated in subjects
      receiving valproate compared to nonepileptic controls. Subjects with epilepsy
      receiving gabapentin or lamotrigine were no different from the nonepileptic
      controls in any of the endocrine variables. Subjects with epilepsy who are
      receiving AEDs that alter cytochrome P450 enzymes are at risk for significant
      abnormalities in sex-steroid hormones. In contrast, subjects receiving AEDs that
      do not alter cytochrome P450 enzymes show no differences in sex-steroid hormones
      compared with nonepileptic controls. With new AEDs available that do not alter
      cytochrome P450 enzymes, physician selection of therapy should consider not only
      seizure control, but also potential effects on reproductive physiology.

PMID- 15492731
TI  - Pediatric ophthalmology in Ireland.

PMID- 15492732
TI  - Costenbader Lecture. The efficacy of rectus muscle transposition surgery in
      esotropic Duane syndrome and VI nerve palsy.
AB  - BACKGROUND: Partial tendon transposition was first described by Hummelshein in
      1907. Full tendon transposition was reported by Schillinger in 1959. Recently,
      full tendon transposition with posterior augmentation was reported by Foster in
      1997. I will review current thinking concerning the anatomy and physiology of
      rectus muscle transposition and present our current clinical experience with this
      procedure in Duane syndrome. METHODS: A retrospective review of vertical rectus
      muscle transposition procedures in patients with VI Nerve palsy was performed
      comparing the postoperative field of single binocular vision, amount of improved
      abduction, and change in the primary esotropic angle. In addition, a consecutive
      series of vertical rectus muscle transposition cases for the treatment of
      esotropic Duane syndrome is presented, evaluating the improvement and head
      position, abduction, and reduction of the primary position esotropia. RESULTS: In
      VI Nerve palsy patients, vertical rectus transposition surgery produces 41
      degrees to 71 degrees of binocular visual field with 10 degrees to 21 degrees of
      binocular field in abduction. In esotropic Duane syndrome the surgical procedure
      produces 42 degrees to 66 degrees of binocular field and a correction of
      approximately 15 degrees of face turn. Variability in the efficacy of the
      procedure is related to the degree of ipsilateral medial rectus contracture.
      CONCLUSION: Vertical rectus transposition with posterior fixation can create a
      binocular diplopia-free field of 40 to 70 degrees in patients with VI Nerve palsy
      and about 40 to 65 degrees in patients with Duane syndrome. Partial rectus muscle
      transposition is an effective procedure in cases where surgery on multiple rectus
      muscles has been or will be required. Orbital wall fixation of the lateral rectus
      muscle is an effective and reversible method to inactivate a lateral rectus
      muscle and may be useful in cases of Duane syndrome with marked anomalous
      innervation and severe cocontraction.

PMID- 15492733
TI  - Risk of amblyopia recurrence after cessation of treatment.
AB  - BACKGROUND: Although amblyopia can be successfully treated with patching or
      atropine, there have been few prospective studies of amblyopia recurrence once
      treatment is discontinued. METHODS: We enrolled 156 children with successfully
      treated anisometropic or strabismic amblyopia (145 completed follow-up), who were
      younger than 8 years of age and who received continuous amblyopia treatment for
      the previous 3 months (prescribed at least 2 hours of daily patching or
      prescribed at least one drop of atropine per week) and who had improved at least
      3 logMAR levels during the period of continuous treatment. Patients were followed
      off treatment for 52 weeks to assess recurrence of amblyopia, defined as a 2 or
      more logMAR level reduction of visual acuity from enrollment, confirmed by a
      second examination. Recurrence was also considered to have occurred if treatment
      was restarted because of a nonreplicated 2 or more logMAR level reduction of
      visual acuity. RESULTS: Recurrence occurred in 35 (24%) of 145 cases (95%
      confidence interval 17% to 32%) and was similar in patients who stopped patching
      (25%) and in patients who stopped atropine (21%). In patients treated with
      moderately intense patching (6 to 8 hours per day), recurrence was more common
      (11 of 26; 42%) when treatment was not reduced prior to cessation than when
      treatment was reduced to 2 hours per day prior to cessation (3 of 22; 14%, odds
      ratio 4.4, 95% confidence interval 1.0 to 18.7). CONCLUSIONS: Approximately one
      fourth of successfully treated amblyopic children experience a recurrence within
      the first year off treatment. For patients treated with 6 or more hours of daily
      patching, our data suggest that the risk of recurrence is greater when patching
      is stopped abruptly rather than when it is reduced to 2 hours per day prior to
      cessation. A randomized clinical trial of no weaning versus weaning in
      successfully-treated amblyopia is warranted to confirm these observational
      findings.

PMID- 15492734
TI  - Risk factors for treatment failure of anisometropic amblyopia.
AB  - PURPOSE: This study sought to explore factors which might predict the lack of
      vision improvement following therapy of anisometropic amblyopia. METHODS: We
      retrospectively reviewed the records of 104 children aged 3 to 8 years who had
      anisometropic amblyopia with a difference in the refractive power between the two
      eyes of at least 1 diopter, a difference in corrected visual acuity between the
      two eyes of at least 3 logMAR units, visual acuity in the amblyopic eye of 20/50
      or worse, and no ocular structural abnormalities. Patients were treated with
      either patching or atropine penalization therapy. Patients with strabismus were
      included. Treatment failure was defined in two ways: (1) functional failure
      indicating a final visual acuity in the amblyopic eye worse than 20/40 and (2)
      relative failure indicating less than three lines of logMAR visual acuity
      improvement regardless of final vision. RESULTS: Failure risk factors were as
      follows: age above 6 at the onset of treatment (adjusted odds ratio [OR] (95%
      confidence limits [CL] = 4.69 [1.55, 14.2]), the presence astigmatism of more
      than 1.50 diopters in the amblyopic eye (adjusted [OR] (95% CL) = 5.78 [1.27,
      26.5]), poor compliance with treatment (adjusted [OR] (95% CL) = 5.47 [1.70,
      17.6]), and initial visual acuity in the amblyopic eye of 20/200 or worse
      (adjusted [OR] (95% CL) = 3.79 [1.28, 11.2]). Strabismus was not found to be a
      significant risk factor. Neither the type or amount of refractive error nor the
      difference in the refractive power between the two eyes was a significant risk
      factor for treatment failure. CONCLUSION: Eyes with poor initial visual acuity,
      the presence of significant astigmatism, and age over 6 years were less likely to
      achieve successful outcome. The clinical profile of patients with anisometropic
      amblyopia may be useful in predicting response to therapy, but compliance with
      treatment has a major effect on response to therapy.

PMID- 15492735
TI  - Binocularity following surgical correction of strabismus in adults.
AB  - PURPOSE: This is a retrospective study to determine the pre- and postoperative
      binocular status of adults who have undergone surgical correction of strabismus.
      METHODS: A list of all consecutive adult patients who underwent surgery for
      strabismus between June 1990 and December 2001 (surgery by MBM) was compiled and
      their medical charts were reviewed. Patients who had at least 6 weeks
      postoperative follow-up were included if their charts were available for review
      and if information on binocularity was recorded. Binocularity was measured by the
      Titmus stereo test (Stereo Optical Co., Inc., Chicago), and/or the Worth 4-Dot
      test for distance (Scioto Medical Products, Powell, OH [discontinued]), and/or
      the Worth 4-Dot near test (Gulden Ophthalmics, Inc., Elkin Park, PA).
      Improvements or decreases in stereo acuity were noted 6 weeks postoperatively and
      at the final office visit. Prism management was incorporated pre- and/or
      postoperatively in some of our patients. A total of 112 patients underwent
      surgery for strabismus. Of these, 72 patients, aged 16 to 80 years, were
      included; 24 were excluded as their charts did not contain any information on
      stereo acuity 6 weeks postoperatively or were lost to follow-up after surgery,
      and 16 were excluded because their charts were unavailable from storage. RESULTS:
      The mean follow-up for the study patients was 16.5 months (range 6 weeks to 79
      months). Overall, 30 of the 72 patients improved in binocular function (42%), 38
      remained the same (53%), and 4 decreased (5%). If you exclude those patients with
      40 sec of stereo acuity preoperatively whose stereopsis, by definition, could not
      improve further, and look only at the 59 surgical patients who could improve,
      then 51% improved. A variety of surgical procedures was performed, the most
      common being a bilateral medial rectus recession. Eleven patients required a
      second surgical procedure and two required a third surgical procedure.
      CONCLUSION: The benefits of surgical correction of strabismus in adults include
      improvement in binocular function as seen in 51% of the patients in the study.

PMID- 15492736
TI  - Predictive factors underlying the restoration of macular binocular vision in
      adults with acquired strabismus.
AB  - PURPOSE: To investigate whether macular binocular vision can be permanently lost
      following acquired strabismus and to identify predictive factors underlying its
      restoration. SUBJECTS AND METHODS: Twenty-three patients with strabismus acquired
      after binocular vision maturation were enrolled. Factors studied included
      duration of eye misalignment, age at treatment, pre-surgical strabismus type, pre
      surgical diplopia, and pre-surgical capacity for binocularity. The restoration of
      macular binocular vision was evaluated between 1 and 3 years following successful
      eye re-alignment and was defined as 60 seconds of arc stereopsis or better on the
      Titmus circles and/or the Preschool Randot Stereoacuity test. RESULTS: Sixteen of
      23 (70%) or 7/23 (30%) of patients achieved macular binocular vision following
      successful surgical eye realignment using the Titmus circles versus the Preschool
      Randot Stereoacuity test. Patients with < or =12 months constant eye misalignment
      were more likely to achieve macular binocular vision following treatment than
      patients with >12 months constant eye misalignment. CONCLUSIONS: Macular
      binocular vision continues to be susceptible to permanent loss in adult patients.
      Factors that are predictive of the restoration of macular binocular vision
      include duration of constant eye misalignment and the pre-surgical capacity for
      binocularity.

PMID- 15492737
TI  - Normal computerized tomography of brain in children with shaken baby syndrome.
AB  - OBJECTIVE: To characterize the clinical presentation and clinical course of
      shaken baby syndrome (SBS) with normal cranial computerized tomography (CT) on
      admission and to suggest further diagnostic procedures in such circumstances.
      METHODS: Using a worldwide listserv designed to facilitate discussion in the
      field of child abuse and neglect, we solicited case information for children
      hospitalized in different medical centers, who were diagnosed with SBS and had a
      normal CT scan on admission. RESULTS: Nine cases were identified. While all
      children had an abnormal neurologic examination on admission, eight had a normal
      CT, and one had "widening of cranial sutures." In four cases, subdural hemorrhage
      was diagnosed on magnetic resonance imaging (MRI) 3 to 7 days after admission.
      Five children had bone fractures. The neurological outcome was normal in four of
      nine cases. Five children had long-term neurologic damage. The diagnosis of SBS
      was supported by either perpetrator confession, characteristic evolution of brain
      abnormalities on CT or MRI, inconsistent or absent explanatory history, and/or
      other social risk factors. CONCLUSION: The diagnosis of SBS can be established
      even when brain CT is normal on admission. The documentation of retinal
      hemorrhages is of primary importance in establishing the diagnosis of SBS in
      these cases.

PMID- 15492738
TI  - Medial rectus pulley posterior fixation: a novel technique to augment recession.
AB  - PURPOSE: Medial rectus (MR) pulley posterior fixation, a technique of suturing
      the pulley to its muscle without scleral sutures, may be as effective as
      traditional scleral posterior fixation in primary treatment of acquired esotropia
      (ET) with a high AC/A ratio. This study examines the effectiveness of MR pulley
      posterior fixation for other variants of ET. METHODS: We retrospectively analyzed
      the pre- and postoperative alignment of 16 patients: 9 previously operated
      patients with excess near ET, 4 patients with sensory ET with excess near ET, and
      3 patients with large-angle infantile ET. Surgeries involved extraocular muscle
      recessions and resections in standard doses combined with MR pulley posterior
      fixation. RESULTS: All 9 reoperated patients were between 0 and 10 prism diopters
      of distance ET postoperatively. The excess near ET decreased from an average of
      12.1 prism diopters preoperatively (range 6-20) to 1.3 prism diopters
      postoperatively (range, 0-4). Two of the 4 patients with sensory ET were
      overcorrected at distance (exotropia of 10 and 15 prism diopters, respectively).
      The excess near ET of these 4 patients decreased from an average of 13.5 prism
      diopters preoperatively (range, 10-20) to 2.5 prism diopters postoperatively
      (range, 0-8). In patients with large-angle infantile ET, the addition of pulley
      posterior fixation resulted in a greater effect than would be predicted for
      standard MR recessions, particularly at near. Pooling data for all groups, pulley
      posterior fixation was associated with a highly significant reduction of excess
      near esotropia postoperatively (P < 0.00001). DISCUSSION: MR pulley posterior
      fixation augments MR recession with relatively greater effect at near. Surgical
      dosage for unilateral recessions and resections combined with MR pulley posterior
      fixation should be reduced in patients with poor potential for postoperative
      fusion.

PMID- 15492739
TI  - Prevalence of psychosocial disturbances in children with nonorganic visual loss.
AB  - PURPOSE: To report on the prevalence of psychiatric disease and psychosocial
      stress in children with nonorganic visual loss. MATERIALS AND METHODS: Case
      series of 71 consecutive pediatric patients with a variety of nonorganic visual
      signs and symptoms. Chart review of ophthalmologic findings and details of
      medical and social history with main outcome measures of prevalence of
      psychiatric disease and psychosocial stress. RESULTS: Psychological/psychiatric
      disturbances in the form of anxiety, depression, and attention deficit
      hyperactivity disorder had been previously diagnosed in 19 (26.7%) patients. We
      had a very high index of suspicion of psychiatric illness in another four
      patients. Furthermore, we uncovered significant home and school stress in 22
      (31%) patients. Sixteen (22.5%) patients wanted glasses and in 10 (14.1%)
      patients no cause for the behavior could be determined. Of those patients who
      wanted glasses, girls outnumbered boys 3:1. CONCLUSIONS: An underlying
      psychiatric or psychosocial disturbance should be ruled out in children who
      present with nonorganic visual loss.

PMID- 15492740
TI  - Nasal myectomy of the inferior oblique muscles for recurrent elevation in
      adduction.
AB  - PURPOSE: Recurrence of inferior oblique overaction (IOOA) after recession or
      anterior transposition of the inferior oblique (IO) muscles is a common problem.
      We have been treating such cases by nasal myectomy of the IO, where a segment of
      approximately 5 mm is removed from the nasal portion, leaving the temporal
      portion of the IO with its insertion and its ancillary origin, the
      neurofibrovascular junction, intact. Here we report long-term findings on this
      procedure. METHODS: Records were analyzed on 72 eyes belonging to 40 patients
      with recurrent IOOA of grade +1 or more, who received nasal myectomy of the
      inferior oblique (NMIO) in one (8 cases) or both (32 cases) eyes, and who had a
      minimum of 3 months follow-up. RESULTS: At follow-up (range 3.6 months to 12
      years; median 26 months), 27 patients (68%) showed no IO overaction, whereas 11
      (28%) showed improvement of at least one grade point and 2 (5%) showed no
      improvement. Of the patients with residual IO overaction, three received
      additional surgery: in two of these patients IO overaction was subsequently
      eliminated while no additional follow-up was available for the third patient. The
      effects of NMIO on dissociated vertical deviation were variable. CONCLUSION: In
      95% of these patients nasal myectomy of the IO resulted in reduction and in many
      cases elimination of IO overaction. An advantage of this procedure is that the
      temporal portion of the muscle, with its ancillary origin and insertion, is
      preserved.

PMID- 15492741
TI  - Nasolacrimal duct obstruction in children: outcome of intubation.
AB  - BACKGROUND: Nasolacrimal silicone intubation is a treatment for congenital
      nasolacrimal duct obstruction (NLDO) after failed probing and irrigation.
      Functional outcome has been previously reported as poorer in children with Down
      syndrome. METHOD: The outcome of 122 cases of silicone bicanalicular nasolacrimal
      intubation, performed between 1988 and 2002 on 97 children aged 11 months to 9.5
      years, was retrospectively reviewed. In all children, intubation was performed
      under direct vision using nasal endoscopy. Statistical analysis, including
      multiple logistic regression analysis, was used to assess the effects of duration
      of intubation, and age at surgery, on treatment outcome, and to determine
      potential predictors of treatment failure. RESULTS: The overall success rate was
      85%, with 89% success for eyes in children with Down syndrome and 85% success for
      eyes in children without Down syndrome. Success rates were consistently high (83%
      to 100%) for children who underwent surgery between 1 and 4 years of age. The
      average duration of intubation was 5.5 months. Increasing duration of intubation
      was not associated with increasing chance of success, but with a significantly
      higher risk of failure if greater than 18 months (P = 0.03). Retention of stents
      for longer than 12 months was associated with a significantly lower success rate
      (67%). The presence of Down syndrome, increasing age at surgery, or gender were
      not predictive factors for treatment failure. Unplanned removal of tubes because
      of dislodgement was the most common complication, occurring in 25% of eyes, but
      did not affect functional outcome. CONCLUSIONS: Nasolacrimal silicone intubation,
      under direct nasal endoscopic visualization, is a consistently successful
      procedure for the treatment of NLDO among children aged older than 12 months of
      age. Tubing should be left in place for a maximum of 12 months because the
      success rate declines after this period and the risk of failure is significantly
      increased after 18 months of intubation. Prematurely dislodged tubes need not be
      replaced unless symptoms of nasolacrimal obstruction occur, because this does not
      lead to an increased risk of treatment failure.

PMID- 15492742
TI  - Rectus muscle orbital wall fixation: a reversible profound weakening procedure.
AB  - INTRODUCTION: Surgical treatment of third nerve palsy, sensory exotropia and
      strabismus secondary to anomalous innervation of the rectus muscles, frequently
      require large rectus muscle recessions in an attempt to maintain alignment in the
      primary position and reduce the effects of misinnervation. The aim of this study
      was to describe and evaluate the results of inactivation of a rectus muscle by
      its attachment to the adjacent orbital wall. METHODS: Seven subjects diagnosed
      with third-nerve palsy (three cases), Duane syndrome (two cases), sensory
      exotropia (one case), and congenital aberrant innervation of vertical rectus
      muscles (one case) underwent rectus muscle inactivation by orbital wall fixation.
      The rectus muscle was disinserted from the globe and reattached to the adjacent
      orbital periosteum using non-absorbable sutures. This surgery was performed on
      the lateral rectus muscle in six subjects, and surgery was performed on both
      ipsilateral vertical rectus muscles in one. RESULTS: Postoperatively four of six
      patients were aligned within 12 prism diopters of orthotropia in primary
      position. All patients had improvement of the anomalous head posture. In Duane
      syndrome, lateral rectus inactivation markedly reduced co-contraction and globe
      retraction. No overcorrections resulted. CONCLUSION: A rectus muscle may be
      functionally inactivated when its insertion is attached to the orbital
      periosteum. Advantages of this procedure over extirpation and free tenotomy
      include permanent disinsertion of the muscle from globe and reversibility.

PMID- 15492743
TI  - An evaluation of the semiadjustable suture strabismus surgical procedure.
AB  - BACKGROUND: Muscle slippage is an adverse outcome of strabismus surgery. Its
      incidence is increased if adjustable sutures are used or if surgery is performed
      on the inferior or medial rectus muscles. Although there are no firm numbers for
      this complication, studies have suggested incidence rates between 7% and 41% when
      adjustable suture surgery is performed on the inferior rectus muscle. In theory,
      the semiadjustable suture procedure should decrease this adverse outcome. This
      procedure involves suturing the corners of the muscle firmly to the sclera and
      placing the center of the muscle on an adjustable suture. This study evaluates
      semiadjustable suture surgery with respect to muscle slippage. METHODS: The
      primary treatment group consisted of 57 patients who underwent semiadjustable
      suture surgery on a total of 61 muscles that either had never previously
      undergone surgery or had undergone surgery and had not previously slipped
      postoperatively. Fifty-five were inferior rectus muscles and 6 were medial rectus
      muscles. An additional 7 patients had semiadjustable suture surgery on muscles
      that had slipped after prior surgery and were analyzed separately. The outcome
      evaluation was at least 6 months after surgery. RESULTS: None of the 57 patients
      in the primary treatment group demonstrated muscle slippage after semiadjustable
      suture surgery. One of the 7 patients who had history of prior muscle slippage
      also had slippage after semiadjustable suture surgery. CONCLUSION: The
      semiadjustable suture procedure appears to decrease the incidence of muscle
      slippage.

PMID- 15492744
TI  - Strabismic complications following endoscopic sinus surgery: diagnosis and
      surgical management.
AB  - INTRODUCTION: Endoscopic surgical techniques improve the surgeon's view of sinus
      structures but are subject to extraocular muscle complications that cause
      permanent diplopia. METHODS: A series of 15 patients with strabismus following
      endoscopic sinus surgery was reviewed retrospectively to characterize the type of
      muscle injury and report the results of surgical correction. RESULTS: A variety
      of insults to the medial rectus (MR) muscle occurred, ranging from contusion,
      hematoma, oculomotor nerve damage with paralysis, muscle transection, and muscle
      destruction. Inferior rectus and superior oblique muscle trauma was observed.
      High-resolution computed tomography and magnetic resonance imaging scans proved
      essential in determining the extent and nature of muscle injury. Surgical
      approaches included anterior orbitotomy with muscle recovery and transposition
      procedures. CONCLUSIONS: Several extraocular muscles may be traumatized. Timing
      and type of surgical treatment depend on severity, type of injury, and number of
      muscles involved. If the remaining posterior segment of the MR muscle is longer
      than 20 mm and is contractile, muscle recovery via anterior orbital approach is
      suggested. If injury is more severe, muscle transposition procedures may be
      helpful. In cases where there is coexistent medial and inferior rectus injury,
      transposition procedures may not be possible. Inactivation of the antagonist and
      use of an orbital periosteal flap as a globe tether to center it may be options.

PMID- 15492745
TI  - PHACE syndrome: association with persistent fetal vasculature and coloboma-like
      iris defect.
AB  - PHACE Syndrome is a neurocutaneous disease spectrum encompassing the following
      features: Posterior fossa brain malformations, large facial Hemangiomas, Arterial
      anomalies, Coarctation of the aorta and cardiac defects, and Eye abnormalities.
      We report the ocular and systemic findings, as well as the management course, of
      an infant who has all the characteristic features of PHACE syndrome and also
      describe what we believe to be the first reported case of this syndrome with
      Persistent Fetal Vasculature (PFV).

PMID- 15492746
TI  - Cavernous hemangioma of the iris in an infant.
AB  - Iris hemangioma is a rare intraocular tumor which can present with spontaneous
      hyphema. Juvenile xanthogranuloma, malignant melanoma with proliferation of
      vessels or hemorrhages in the region of cystic degeneration, and inflammatory
      granulomas are frequently confused with the true hemangiomas. Some authors have
      even questioned the very existence of iris hemangioma. Clinical case reports of
      iris hemangiomas with histopathologic evidence and clinical course after surgery
      are uncommon. We could not find any reports of iris vascular tumors confirmed
      using immunohistochemical staining with vascular markers. We report a case of a
      cavernous hemangioma of the iris in a 3-month-old infant treated surgically, and
      the histopathological findings and immunohistochemical analysis with vascular
      markers (factor VIII and CD34) are also shown.

PMID- 15492747
TI  - Iris cyst simulating melanoma.
AB  - Congenital cysts of the iris stroma are extremely uncommon and only a few cases
      have been reported. The vast majority of reported cases have been found in
      infants or children as a unilateral, translucent mass in the middle or peripheral
      third of the iris. 1-3 Although these cysts may remain dormant for years, they
      have a tendency to enlarge, causing corneal decompensation, secondary glaucoma,
      and eye pain. 2 Occasionally, they have been mistaken for iris melanomas leading
      to enucleation. 4,5 We describe a 14-year-old girl with a congenital cyst of the
      iris stroma, which over a period of 8 years enlarged, became opaque resembling
      melanoma, and required surgical excision.

PMID- 15492748
TI  - Posterior embryotoxon may not be a forme fruste of Axenfeld-Rieger's Syndrome.
AB  - Axenfeld-Rieger Syndrome is a disorder of morphogenesis which is autosomal
      dominantly inherited. One of the main ocular features associated with Axenfeld
      Rieger is posterior embryotoxon, which is a prominent anteriorly displaced
      Schwalbe's line. This can be found in up to 15% of normal eyes, without any
      clinical significance or may represent a forme fruste of an anterior segment
      dysgenesis. Many large case series studies of Axenfeld-Rieger had used the
      presence of posterior embryotoxon with iris strands extending from the peripheral
      iris to Schwalbe's line, as inclusion criterion for this condition. We report a
      case of Axenfeld-Rieger syndrome without posterior embryotoxon and the
      abnormalities of the angle, but with other features to support the diagnosis of
      Axenfeld-Rieger Syndrome.

PMID- 15492749
TI  - Brown's Syndrome in the absence of an intact superior oblique muscle.
AB  - Brown's Syndrome was initially described as a superior oblique tendon sheath
      syndrome-a short anterior tendon resulting in a restricted elevation of the globe
      in the nasal field. Brown believed that a congenital paralysis of the inferior
      oblique muscle resulted in this secondary shortening of the anterior sheath of
      the superior oblique tendon. The definition of Brown's Syndrome has changed over
      time. It is currently defined as the inability to elevate the eye in the adducted
      position, both actively and passively on force duction testing, and can be
      acquired. The pathophysiology of acquired Brown's Syndrome may involve an
      abnormality of the superior oblique trochlea/tendon complex. However, it may also
      result from other causes unrelated to the superior oblique tendon or muscle, such
      as tumors of the superior nasal orbit, inferior orbital mechanical restriction,
      or an inferiorly displaced lateral rectus muscle and pulley. We present two cases
      in which a Brown's Syndrome was diagnosed after the superior oblique muscle had
      been disinserted or removed.

PMID- 15492750
TI  - A simple model for practicing surgery on the nasolacrimal drainage system.
AB  - Practicing surgical techniques on models prior to operating on patients can be
      helpful in developing skills needed to perform surgery proficiently. A simple,
      inexpensive, and readily available model for instruction and practice of surgical
      maneuvers on the nasolacrimal drainage system is described.

PMID- 15492751
TI  - Strong expression of methylthioadenosine phosphorylase (MTAP) in human colon
      carcinoma cells is regulated by TCF1/[beta]-catenin.
AB  - Methylthioadenosine phosphorylase (MTAP) is known as a ubiquitously expressed
      house keeping gene important in biochemical salvage processes. The MTAP gene is
      localized on the human chromosomal region 9p21, a region often deleted in cancer.
      Recently, several groups including our own have shown that MTAP serves as a
      tumour suppressor gene. The aim of this study was to analyse the role of MTAP in
      colon carcinoma and normal colon epithelium and the regulation of gene
      expression. To examine MTAP RNA and protein expression, we screened six colon
      carcinoma cell lines and human primary colon epithelial cells by RT-PCR and
      immunoblotting. MTAP expression was confirmed in vivo by immunohistochemical
      staining of normal colon tissue compared to adenoma and colon carcinoma.
      Interestingly, we found strong MTAP mRNA and protein expression by colon
      carcinoma cell lines but no expression by colonic epithelial cells. To analyse
      the regulation of MTAP expression, promoter studies were performed and revealed
      control of MTAP expression by LEF/TCF/beta-catenin. Furthermore, we demonstrated
      a significant correlation between MTAP protein expression and tumour progression
      as the intensity of MTAP protein staining increased from normal tissue to
      carcinoma. In addition, the recently postulated association between MTAP activity
      and interferon (IFN) sensitivity was confirmed in colon epithelial cells showing
      only little response to IFN-gamma, in contrast to the carcinoma cell lines. In
      summary, these data indicate for the first time that MTAP is not expressed in
      normal human colonic epithelium but is strongly upregulated in colon carcinoma.
      This finding may be of clinical significance concerning the homeostasis of normal
      colon epithelium and potential treatment of colon carcinoma.

PMID- 15492752
TI  - Acquisition of lymph node, but not distant metastatic potentials, by the
      overexpression of CXCR4 in human oral squamous cell carcinoma.
AB  - Recently, it has been suggested that chemokine/receptor interactions determine
      the destination of the invasive tumor cells in several types of cancer. It has
      also been proposed that the stromal cell-derived factor-1 (SDF-1; CXCL12)/CXCR4
      system might be involved lymph node metastasis in oral squamous cell carcinoma
      (SCC). In order to further clarify the role of the SDF-1/CXCR4 system in oral
      SCC, we generated CXCR4 stable transfectants (IH-CXCR4) using oral SCC cells, and
      compared them to IH, which did not express CXCR4 and which did not have lymph
      node metastatic potentials in vivo. We introduced enhanced green fluorescent
      protein (GFP) fused-CXCR4 into IH cells, and detected the GFP fluorescence in the
      cytoplasm and cell membrane in approximately 60% of the G418-resistant cells.
      This bulk-transfectant expressed a high level of CXCR4 mRNA and protein, and
      exhibited the characteristic calcium fluxes and chemotactic activity observed in
      treatment with SDF-1. SDF-1 biphasically activated extracellular signal-regulated
      kinase (ERK)1/2, but continuously activated Akt/protein kinase B (PKB) in IH
      CXCR4 cells. Most importantly, IH-CXCR4 cells frequently metastasized to the
      cervical lymph node, but not to the distant organs in the orthotopic inoculation
      of nude mice. Furthermore, these lymph node metastases were inhibited by the
      treatment of a mitogen-activated protein kinase/ERK kinase inhibitor, U0126, or a
      phosphatidylinositol 3 kinase inhibitor, wortmannin. These results indicate that
      SDF-1/CXCR4 signaling mediates the establishment of lymph node metastasis in oral
      SCC via ERK1/2 or Akt/PKB pathway.

PMID- 15492753
TI  - Accumulation of CCR5+ T cells around RANTES+ granulomas in Crohn's disease: a
      pivotal site of Th1-shifted immune response?
AB  - Immunological abnormalities are implicated in the pathogenesis of inflammatory
      bowel disease (IBD), that is, Crohn's disease and ulcerative colitis. In
      particular, Crohn's disease is considered to be a T helper type 1 (Th1)-shifted
      disease. Chemokines and their receptors are involved in various immune responses
      including Th1- and Th2 responses. In this study, we analyzed chemokines and their
      receptors by immunohistochemistry, using frozen sections derived from 33 patients
      with Crohn's disease and 24 with ulcerative colitis. In inflamed mucosa, small
      mononuclear cells predominantly expressed CCR5 and CXCR3, the receptors
      selectively expressed on Th1 cells, without significant differences between
      Crohn's disease and ulcerative colitis. We then focused on the noncaseating
      granulomas that are characteristic of Crohn's disease. Granuloma cells, observed
      in all the layers of intestinal tissues, were positive for RANTES/CCL5 protein
      along their cell membranes. Lymphocytes surrounding granulomas were mostly CCR5+
      and CXCR3+ T cells with CD4+ and CD8+ cells at similar frequencies. Granuloma
      cells were positive for RANTES mRNA by in situ hybridization. By contrast,
      lymphoid aggregates in Crohn's disease and lymphoid follicles in the normal
      intestinal mucosa were characterized by abundant B cells, a predominance of CD4+
      T cells over CD8+ T cells, and low frequencies of cells expressing CCR5 or CXCR3.
      Together with the notion that granuloma cells are possible antigen-presenting
      cells, our results suggest that the noncaseating granulomas could be one of the
      crucial sites of Th1-shifted immune responses in Crohn's disease.

PMID- 15492754
TI  - Reduced expression of IL-12 receptor beta2 and IL-18 receptor alpha genes in
      natural killer cells and macrophages derived from B6-mi/mi mice.
AB  - The mi transcriptional factor (MITF) is a basic helix-loop-helix leucine zipper
      type transcriptional factor. The mi mutant allele encodes an abnormal MITF, in
      which one out of four consecutive arginines is deleted in the basic domain. The
      VGA-9-tg (tg) allele is another mutant allele and considered to be a null mutant
      allele. C57BL/6 (B6)-mi/mi mice showed abnormal phenotypes of natural killer (NK)
      cells and macrophages, whereas B6-tg/tg mice did not. The expression levels of
      the genes for the interleukin-12 receptor (IL-12R) beta2 and IL-18Ralpha were
      reduced in both the NK cells and macrophages of B6-mi/mi mice, while the
      expression levels of the corresponding genes in B6-tg/tg mice were unaffected.
      The B6-mi/mi NK cells and B6-mi/mi macrophages showed impaired responses to
      stimulation with IL-12, IL-18, and IL-12 plus IL-18 stimulation. The abnormal NK
      cell and macrophage of B6-mi/mi mice appear to be due to decreased expression of
      the IL-12Rbeta2 and IL-18Ralpha genes.

PMID- 15492755
TI  - Role of endogenous and exogenous ligands for the peroxisome proliferators
      activated receptors alpha (PPAR-alpha) in the development of inflammatory bowel
      disease in mice.
AB  - The peroxisome proliferator-activated receptor-alpha (PPAR-alpha) is a member of
      the nuclear receptor superfamily of ligand-dependent transcription factors
      related to retinoid, steroid and thyroid hormone receptors. The aim of the
      present study was to examine the effects of endogenous and exogenous PPAR-alpha
      ligand on the development of experimental colitis. To address this question, we
      used an experimental model of colitis, induced by dinitrobenzene sulfonic acid
      (DNBS). When compared to DNBS-treated PPAR-alpha wild-type (WT) mice, DNBS
      treated PPAR-alpha knockout mice (PPAR-alphaKO) mice experienced a higher rate of
      the extent and severity of the histological signs of colon injury. After
      administration of DNBS PPAR-alphaWT mice experienced hemorrhagic diarrhea, weight
      loss and large areas of necrosis in the mucosa of the colon were also observed.
      Neutrophil infiltration was associated with upregulation of ICAM-1.
      Immunohistochemistry for nitrotyrosine showed an intense staining in the inflamed
      colon. Absence of a functional PPAR-alpha gene in PPAR-alphaKO mice resulted in a
      significant augmentation of all the above-described parameters. On the contrary,
      the treatment of PPAR-alphaWT with Wy-14643 (1 mg/kg daily i.p) significantly
      reduced: (i) the degree of hemorrhagic diarrhea and weight loss, (ii) the degree
      of colon injury, (iii) the rise in MPO activity (mucosa), (iv) the increase in
      staining (immunohistochemistry) for nitrotyrosine, as well as (v) the
      upregulation of ICAM-1 caused by DNBS in the colon. In order to elucidate whether
      the protective effects of Wy-14643 is related to activation of the PPAR-alpha
      receptor, we also investigated the effect the of Wy-14643 treatment on PPAR-alpha
      deficient mice. The absence of the PPAR-alpha receptor significantly abolished
      the protective effect of the PPAR-alpha agonist against DNBS-induced colitis.
      Thus, endogenous and exogenous PPAR-alpha ligands reduce the degree of colitis
      caused by DNBS. We propose that PPAR-alpha ligand may be useful in the treatment
      of inflammatory bowel disease.

PMID- 15492756
TI  - Genetic analysis of sinonasal adenocarcinoma phenotypes: distinct alterations of
      histogenetic significance.
AB  - Sinonasal adenocarcinomas, a relatively rare entity, are composed of distinctly
      different morphologic subtypes with variable biological behavior. To investigate
      the genetic events associated with their development and clinicopathologic
      features, we analyzed the alterations in K-ras, APC, beta-catenin, hMLH1 and
      hMSH2 and p53 genes expression in a cohort of 15 primary tumors comprising the
      two main sinonasal adenocarcinoma subtypes (enteric and seromucinous). The
      patients consisted of 13 men and two women, who ranged in age from 50 to 87
      years. Tumors were predominantly located in the ethmoid sinus. Eight tumors were
      Enteric-type, and seven were seromucinous type. Nine patients were smokers and
      four were nonsmokers; and no information was available on two patients. Two of
      the eight enteric-type, had K-ras mutation at codons 12A and 12B, and one showed
      microsatellite instability at BAT-25. Two patients with enteric-type tumors had a
      history of wood-dust exposure, and one had a K-ras mutation at 12A codon as well
      as p53 overexpression. No patients with the seromucinous type had any genetic
      abnormalities, except for overexpression of p53 in two tumors. Our results show
      that (1) a subset of enteric-type sinonasal adenocarcinoma shares certain genetic
      alterations with colonic adenocarcinomas, (2) the seromucinous-type sinonasal
      adenocarcinoma lacks alterations and may develop through a different pathway, (3)
      high p53 expression is associated with aggressive tumor features in both subtypes
      and (4) the enteric-type runs a more malignant course than the seromucinous
      counterpart.

PMID- 15492757
TI  - Selected miscellaneous ovarian lesions: small cell carcinomas, mesothelial
      lesions, mesenchymal and mixed neoplasms, and non-neoplastic lesions.
AB  - This contribution will cover a variety of uncommon tumors and tumor-like lesions
      of the ovary that can be associated with a myriad of diagnostic problems for the
      pathologist. A few of these lesions are not specific to the ovary and may be more
      common in the uterus or even extraovarian sites, but the mere knowledge that they
      also occasionally occur in, or involve, the ovary will facilitate their
      recognition by the pathologist. In contrast, the entity considered first, the
      highly malignant small cell carcinoma of hypercalcemic type, is an enigmatic
      tumor unique to the ovary.

PMID- 15492758
TI  - Ovarian carcinomas, including secondary tumors: diagnostically challenging areas.
AB  - The differential diagnosis of ovarian carcinomas, including secondary tumors,
      remains a challenging task. Mucinous carcinomas of the ovary are rare and can be
      easily confused with metastatic mucinous carcinomas that may present clinically
      as a primary ovarian tumor. Most of these originate in the gastrointestinal tract
      and pancreas. International Federation of Gynecology and Obstetrics (FIGO) stage
      is the single most important prognostic factor, and stage I carcinomas have an
      excellent prognosis; FIGO stage is largely related to the histologic features of
      the ovarian tumors. Infiltrative stromal invasion proved to be biologically more
      aggressive than expansile invasion. Metastatic colon cancer is frequent and often
      simulates ovarian endometrioid adenocarcinoma. Although immunostains for
      cytokeratins 7 and 20 can be helpful in the differential diagnosis, they should
      always be interpreted in the light of all clinical information. Occasionally,
      endometrioid carcinomas may exhibit a microglandular pattern simulating sex cord
      stromal tumors. However, typical endometrioid glands, squamous differentiation,
      or an adenofibroma component are each present in 75% of these tumors whereas
      immunostains for calretinin and alpha-inhibin are negative. Endometrioid
      carcinoma of the ovary is associated in 15-20% of the cases with carcinoma of the
      endometrium. Most of these tumors have a favorable outcome and they most likely
      represent independent primary carcinomas arising as a result of a Mullerian field
      effect. Although the criteria for distinguishing metastatic from independent
      primary carcinomas rely mainly upon conventional clinicopathologic findings, loss
      of heterozygosity and gene mutation analyses can be helpful. Transitional cell
      carcinomas are distinguished from undifferentiated carcinomas by the presence of
      thick, undulating papillae with smooth luminal borders, microspaces, and tumor
      cells with distinctive 'urothelial' appearance. Krukenberg tumors are metastatic
      adenocarcinomas traditionally perceived as composed of mucin-filled signet-ring
      cells associated with a striking proliferation of the ovarian stroma but many
      variations on this pattern occur.

PMID- 15492759
TI  - Signet ring cell carcinoma of the colorectum: correlations between microsatellite
      instability, clinicopathologic features and survival.
AB  - Colorectal cancer with microsatellite instability has a characteristic
      clinicopathologic profile, featuring right-sided, lymphocyte-rich tumors with a
      better prognosis than microsatellite stable (MSS) carcinoma. Mucinous and signet
      ring cell carcinomas are both over-represented among microsatellite instability
      high cancers. The clinicopathologic features of mucinous microsatellite
      instability-high cancer parallel those of the overall microsatellite instability
      high set, but it is not known whether the same is true for signet ring cell
      carcinoma, particularly given the fact that signet ring histology is a well
      documented adverse prognostic factor. We recorded age, sex, tumor size, site,
      grade, stage, histologic pattern, growth pattern, Crohn-like reaction, vascular
      invasion and tumor-infiltrating lymphocytes in 72 resected signet ring cell
      carcinomas of the colorectum. Microsatellite instability was determined by a
      combination of polymerase chain reaction and immunohistochemical stains for
      hMLH1, hMSH2 and hMSH6. Tumors with instability at >30% of informative markers
      and/or loss of hMLH1 or hMSH2 expression were designated microsatellite
      instability-high; all others were classified as MSS. A total of 22 (31%) signet
      ring cell carcinomas were microsatellite instability-high. Compared to MSS signet
      ring cell carcinoma, they were more likely to be right-sided (81 vs 45%, P=0.005)
      and to affect older patients (68 vs 26%, P=0.0007) of female sex (59 vs 28%,
      P=0.03). Crohn-like reaction (45 vs 16%, P=0.02) and high tumor infiltrating
      lymphocyte counts (32 vs 8%, P=0.03) were more common in the microsatellite
      instability-high setting. There was no significant difference in 5-year survival
      in microsatellite instability-high vs MSS patients (41 vs 34%, P=0.3). In
      conclusion, approximately one-third of signet ring carcinomas of the colorectum
      are microsatellite instability-high. Microsatellite instability-high signet ring
      carcinomas share clinicopathologic features with other microsatellite instability
      high cancers: older age group, female preponderance, right-sided location, Crohn
      like reaction and numerous tumor-infiltrating lymphocytes. Microsatellite
      instability status does not appear to be a significant predictor of survival in
      signet ring cell carcinoma of the colorectum.

PMID- 15492760
TI  - Diffuse large B-cell lymphoma with distinctive patterns of splenic and bone
      marrow involvement: clinicopathologic features of two cases.
AB  - Two unusual cases of large B-cell lymphoma with predominant splenic and bone
      marrow (BM) involvement and similar clinical and histopathologic features are
      described. Both patients presented with nonspecific constitutional symptoms,
      unexplained cytopenias, and splenomegaly. Splenectomy revealed diffuse red pulp
      involvement by large B-cell lymphoma. The perisplenic lymph nodes were also
      involved diffusely with effacement of normal nodal architecture, excluding a
      diagnosis of intravascular large B-cell lymphoma. BM biopsies revealed striking
      erythroid hyperplasia without overt morphologic evidence of involvement by
      lymphoma. Immunoperoxidase staining of the marrow biopsies with antibodies to
      CD20 and erythroid-associated antigens revealed involvement by large B-cell
      lymphoma morphologically resembling the early pronormoblasts. In both cases there
      was prominent, but not exclusive, intravascular/intrasinusoidal lymphomatous
      marrow infiltration. These cases represent an unusual variant of large B-cell
      lymphoma with distinctive patterns of splenic and BM involvement. Furthermore,
      they underscore the difficulties in identifying intrasinusoidal marrow
      infiltration by lymphoma in H&E-stained biopsy slides and demonstrate that this
      pattern of marrow infiltration may be seen in cases of large B-cell lymphoma
      distinct from the intravascular variant.

PMID- 15492761
TI  - Human papillomavirus genotyping and p16INK4a expression in cervical
      intraepithelial neoplasia of adolescents.
AB  - Adolescents have high rates of human papillomavirus (HPV) infection, and
      persistent high-risk HPV infection can lead to the development of cervical
      cancer. The cyclin-dependent kinase inhibitor, p16(INK4a) is overexpressed in
      cervical intraepithelial neoplasia (CIN), probably due to a persistent and
      integrated HPV infection. This study investigated p16(INK4a) expression, grades
      of CIN, and high-risk HPV infection in adolescent cervical biopsies. Biopsies
      were immunohistochemically stained for p16(INK4a). The presence of wide-spectrum,
      low-risk, or high-risk HPV was determined by amplifying DNA extracted from the
      cervical biopsies. Biopsies were classified as cervicitis, 15 cases; CIN 1, 48
      cases; CIN 2, 46 cases, and CIN 3, 52 cases. The distribution of p16(INK4a)
      staining was graded as patchy, diffuse basal, and diffuse full thickness.
      Pearson's chi(2) tests analyzed the relationships between p16(INK4a) staining,
      HPV infection, and CIN. Biopsies of cervicitis were negative for HPV and for
      p16(INK4a) expression. High-risk HPV 16, 18, and 31 increased from 18% in CIN 1
      to 66% in CIN 2/3 (P<0.001). In CIN 1, p16(INK4a) was positive in 44% of biopsies
      with 35% showing patchy, 7% diffuse basal, and one case (2%) showing diffuse full
      thickness staining. In CIN 2/3, p16(INK4a) was positive in 97% of biopsies with
      23% showing patchy, 21% diffuse basal, and 53% diffuse full thickness staining.
      The difference in the proportions of biopsies showing patchy p16(INK4a) staining
      in CIN 1 and diffuse full thickness staining in CIN 2/3 was significant
      (P<0.001). In CIN 1, 61% of high-risk HPV-positive biopsies were p16(INK4a)
      negative, while all high-risk HPV-positive CIN 2/3 biopsies were p16(INK4a)
      positive. Diffuse, full thickness p16(INK4a) expression discriminated low-grade
      from high-grade CIN and appears to be a marker of persistent high-risk HPV
      infection.

PMID- 15492762
TI  - Primary breast diffuse large B-cell lymphoma shows a non-germinal center B-cell
      phenotype.
AB  - Primary breast diffuse large B-cell lymphoma has a poor prognosis relative to
      other extranodal diffuse large B-cell lymphoma. Recently, diffuse large B-cell
      lymphoma has been subclassified as germinal center B-cell-like and nongerminal
      center B-cell types using tissue microarrays. The 5-year overall survival rate of
      the germinal center B-cell group is better than that of the nongerminal center B
      cell group. To elucidate the reason for which primary breast diffuse large B-cell
      lymphoma has a poor clinical outcome, we investigated 15 patients with primary
      breast diffuse large B-cell lymphoma (stage IE; 13 cases, stage IIE; two cases)
      by immunohistochemistry using various markers including CD10, Bcl-6, MUM1 and MIB
      1 and by molecular analysis of the immunoglobulin heavy chain gene variable
      region. Immunohistochemistry showed 0/15 (positive cases/examined cases) for
      CD10, 5/15 for Bcl-6, 15/15 for MUM1, 10/15 for Bcl-2, 2/15 for CD5 and 4/15 for
      CD40. The expression pattern of CD10(-) MUM1(+) in primary breast diffuse large B
      cell lymphoma corresponded to the nongerminal center B-cell group. Moreover, the
      MIB-1 index was distributed from 60 to 95% with a mean of 79%, indicating a high
      proliferation of the lymphoma cells. The immunoglobulin heavy chain gene variable
      region of primary breast diffuse large B-cell lymphoma had a mutation frequency
      of 1-10% (seven cases) and 0-1 additional mutations in ongoing mutation analysis
      (five cases). Primary breast diffuse large B-cell lymphoma had characteristics of
      the nongerminal center B-cell group. In conclusion, primary breast diffuse large
      B-cell lymphoma has a nongerminal center B-cell phenotype and has a high MIB-1
      index. These features might therefore be associated with poor prognosis.

PMID- 15492763
TI  - Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): clinical consequences,
      evolutionary aspects and functional diversity.
AB  - CYP2D6 is of great importance for the metabolism of clinically used drugs and
      about 20-25% of those are metabolised by this enzyme. In addition, the enzyme
      utilises hydroxytryptamines as endogenous substrates. The polymorphism of the
      enzyme results in poor, intermediate, efficient or ultrarapid metabolisers (UMs)
      of CYP2D6 drugs. It is plausible that the UM genotype, where more than one active
      gene on one allele occurs, is the outcome of selective dietary selection in
      certain populations in North East Africa. The UM phenotype affects 5.5% of the
      population in Western Europe. A hypothesis for the evolutionary basis behind
      selection for CYP2D6 gene duplications is presented in relation to selection for
      Cyp6 variants in insecticide resistant Drosophila strains. The polymorphism of
      CYP2D6 significantly affects the pharmacokinetics of about 50% of the drugs in
      clinical use, which are CYP2D6 substrates. The consequences of the polymorphism
      at ordinary drug doses can be either adverse drug reactions or no drug response.
      Examples are presented where CYP2D6 polymorphism affects the efficacy and costs
      of drug treatment. Predictive CYP2D6 genotyping is estimated by the author to be
      beneficial for treatment of about 30-40% of CYP2D6 drug substrates, that is, for
      about 7-10% of all drugs clinically used, although prospective clinical studies
      are necessary to evaluate the exact benefit of drug selection and dosage based on
      the CYP2D6 genotype.

PMID- 15492764
TI  - Dopamine receptor DRD2 genotype and smoking cessation outcome following treatment
      with bupropion SR.
AB  - The A1 allele of the dopamine D2 receptor gene (DRD2) is associated with a
      reduced number of dopamine binding sites in the brain and with the increased
      likelihood of substance abuse and addictive behavior. In a study of smokers
      enrolled in an open-label, randomized effectiveness trial, we investigated
      whether variants in the DRD2 receptor gene are associated with smoking cessation
      outcomes following treatment with a combination of bupropion SR and behavioral
      counseling. Adherence to treatment and point-prevalent smoking status were
      assessed at 3 and 12 months, respectively, following a target quit date. Compared
      to women who carry both A2 alleles, women with at least one A1 allele were more
      likely to report having stopped taking bupropion due to medication side effects
      (odds ratio (OR)=1.91, 95% confidence interval (CI)=1.01-3.60; P<0.04) and at 12
      months were somewhat more likely to report smoking (OR=0.76, 95% CI=0.56-1.03;
      P<0.076). Significant associations or trends were not observed in men. In women,
      individual variability in responsiveness to bupropion-based treatment may be
      partially due to differences in genetic variants influencing dopamine receptor
      function.

PMID- 15492765
TI  - Pharmacological mechanisms of clinically favorable properties of a selective
      beta1-adrenoceptor antagonist, nebivolol.
AB  - Nebivolol is a racemic mixture of d- and l-enantiomers. The drug is characterized
      by beta(1)-adrenoceptor selectivity and long-acting beta-blockade exerted
      predominantly by d-enantiomer. Nebivolol is devoid of intrinsic sympathomimetic
      activity and has no relevant membrane stabilizing action. Antiproliferative
      properties of nebivolol were demonstrated in endothelial and smooth muscle cell
      cultures. Infusion of nebivolol causes a vasodilation in all vascular beds by
      endothelial-dependent mechanism involving stimulation of beta(3)-adrenoceptors as
      well as by endothelial-independent mechanism. Nebivolol possesses not only direct
      vasodilator properties but also augments the action of endothelium-dependent
      vasodilators. The antioxidant property of nebivolol can at least in part explain
      why treatment with this drug enhances eNOS activity and minimizes the reperfusion
      induced myocardial injury. The systemic effects of nebivolol in humans have an
      unusual hemodynamic profile. In contrast to traditional beta-adrenoceptor
      antagonists, nebivolol reduces preload and afterload due to systemic vasodilation
      and improves arterial distensibility. At 5 mg daily nebivolol effectively reduces
      systolic and diastolic blood pressure over a 24-h period. During treatment with
      nebivolol arterial pressure follows the natural circadian rhythm. Trough-to-peak
      ratio for nebivolol is 0.9. It has been demonstrated in numerous placebo
      controlled studies that exercise tolerance is not reduced during nebivolol
      therapy. By chronic administration to patients with left ventricular dysfunction
      nebivolol increases myocardial contractility. Nebivolol produced no significant
      changes in lipid levels, insulin sensitivity or glucose tolerance. These findings
      make nebivolol a promising therapeutic tool for the treatment of arterial
      hypertension and chronic heart failure.

PMID- 15492766
TI  - Cardiovascular protective effects of resveratrol.
AB  - Resveratrol (3,4',5-trihydroxy-trans-stilbene), a phytoalexin found in grape
      skins, peanuts, and red wine, has been reported to have a wide range of
      biological and pharmacological properties. It has been speculated that at low
      doses (such as consumed in the common diet) resveratrol may have cardioprotective
      activity. In this article we describe recent in vitro and in vivo studies in
      animal models. The results of these studies suggest that resveratrol modulates
      vascular cell function, inhibits LDL oxidation, suppresses platelet aggregation
      and reduces myocardial damage during ischemia-reperfusion. Although the reported
      biological data indicate that resveratrol is a highly promising cardiovascular
      protective agent, more studies are needed to establish its bioavailability and in
      vivo cardioprotective effects, particularly in humans.

PMID- 15492767
TI  - Pharmacological and clinical studies with temocapril, an angiotensin converting
      enzyme inhibitor that is excreted in the bile.
AB  - Temocapril is an angiotensin converting enzyme inhibitor (ACEI), a prodrug with a
      thiazepine ring. Its active form, temocaprilat, is slightly more potent than
      enalaprilat in inhibiting ACE isolated from rabbit lung. The inhibitory potency
      of temocaprilat on isolated rat aorta is 3 times that of enalaprilat. Temocapril
      is excreted in the bile and urine and can be used in patients with renal
      insufficiency. It reduces blood pressure without causing any significant change
      in heart rate or cardiac output. Temocapril has been reported to improve
      endothelial dysfunction in vitro by suppressing increased oxidative stress. In
      vivo it improves reactive hyperemia in patients with essential hypertension. It
      has been reported to prevent coronary vascular remodeling in vivo by suppressing
      local ACE and increased oxidative stress. In humans temocapril has been found to
      improve insulin resistance partly by increasing adiponectin levels. Cardiac
      remodeling was improved by temocapril not only in experiment animals but also in
      humans. It improves renal function and decreases urinary albumin excretion in
      diabetics as well as in hypertensive patients. Temocapril is currently marketed
      only in Japan. Considering its beneficial effects and unique pharmacokinetics,
      temocapril, is likely to be introduced in other countries as well.

PMID- 15492768
TI  - Clinical potential of lomerizine, a Ca2+ channel blocker as an anti-glaucoma
      drug: effects on ocular circulation and retinal neuronal damage.
AB  - Glaucoma is defined as an optic neuropathy with characteristic changes in the
      optic nerve head and ultimate loss of visual field. Previous studies have
      suggested that (a) mechanical damage due to raised intraocular pressure and (b) a
      compromised tissue circulation in the optic nerve head play significant roles in
      the development of glaucomatous damage in the optic nerve head. Recently, we
      found that lomerizine, a new Ca(2+) channel blocker, increased ocular circulation
      and protected neuronal cells against retinal neurotoxicity both in vitro and in
      vivo with minimal cardiovascular side effects. We examined the effect of
      lomerizine on the ocular circulation and compared it with those of other Ca(2+)
      channel blockers in normal rabbits and in rabbits with an endothelin-1-disturbed
      circulation in the optic nerve head. In anesthetized rabbits, lomerizine and the
      other Ca(2+) channel blockers increased the ocular circulation and also inhibited
      the hypoperfusion induced in optic nerve head tissue by an intravitreous
      injection of endothelin-1. Whereas the other Ca(2+) channel blockers produced
      changes in blood pressure and heart rate, the effects of lomerizine on these
      parameters were slight. In healthy humans, lomerizine increased blood velocity in
      the optic nerve head, without significantly altering blood pressure or heart
      rate. Moreover, lomerizine reduced retinal damage in rats both in vitro and in
      vivo, presumably through a Ca(2+) channel blocking effect via an action that may
      involve a direct protection of retinal neurons as well as an improvement in the
      ocular circulation. These results indicate that lomerizine may be useful as a
      therapeutic drug against ischemic retinal diseases (such as glaucoma and retinal
      vascular occlusive diseases) that involve a disturbance of the ocular
      circulation.

PMID- 15492769
TI  - Prevention of cardiovascular complications of diabetes mellitus by aspirin.
AB  - Eighteen million Americans have type 2 Diabetes Mellitus (DM) while another 40
      million have impaired glucose tolerance. Atherosclerotic heart disease is the
      leading cause of death in patients with diabetes mellitus. In addition to the
      increased risk for CardioVascular Disease (CVD), patients with diabetes have a
      worse prognosis than nondiabetics when they suffer an ischemic event. Insulin
      resistance is increasingly recognized as a chronic, low-level, inflammatory
      state. Hyperinsulinemia has been proposed as the forerunner of hypertension, low
      high-density lipoprotein cholesterolemia, hypertriglyceridemia, abdominal
      obesity, and altered glucose tolerance, linking all these abnormalities to the
      development of coronary vascular disease. Atherosclerosis and insulin resistance
      share similar pathophysiological mechanisms, due to the actions of
      proinflammatory cytokines. The dynamic inflammatory milieu found in diabetes
      explains the susceptibility of diabetics to CVD and the potential mechanism by
      which aspirin may prevent CVD in diabetics. Aspirin decreases the risk for CVD in
      diabetic patients by a variety of established and novel mechanisms. Therapeutic
      strategies that lesson the CVD risk in diabetic patients, including the use of
      aspirin for primary and secondary prevention, are potentially very important.
      This review article addresses the antiatherosclerotic effects of aspirin, the
      potential anti-diabetic effects of aspirin, and the clinical trial evidence for
      CVD prevention by aspirin in diabetics. We also present recommendations for the
      use of aspirin in the diabetic population and the current guidelines put forth by
      the American Heart Association and by the American Diabetes Association.

PMID- 15492770
TI  - Pharmacodynamic, pharmacokinetic and clinical effects of clevidipine, an
      ultrashort-acting calcium antagonist for rapid blood pressure control.
AB  - Clevidipine is an ultrashort-acting vasoselective calcium antagonist under
      development for short-term intravenous control of blood pressure. Studies in
      animals, healthy volunteers and patients have demonstrated the vascular
      selectivity and rapid onset and offset of antihypertensive action of clevidipine,
      a synthetic 1,4-dihydropyridine that inhibits L-type calcium channels.
      Clevidipine has a high clearance (0.05 L/min/kg) and is rapidly hydrolyzed to
      inactive metabolites by esterases in arterial blood. Its half-life in patients
      undergoing cardiac surgery is less than one min. Unlike sodium nitroprusside, a
      drug commonly used for the short-term control of blood pressure, which dilates
      both arterioles and veins, clevidipine reduces blood pressure through a selective
      effect on arterioles. As documented in animals and in cardiac surgical patients,
      clevidipine reduces peripheral resistance without any undesirable effect on
      cardiac filling pressure. It increases stroke volume and cardiac output. In
      anesthetized patients undergoing cardiac surgery clevidipine, unlike sodium
      nitroprusside, does not increase heart rate. In addition of having a favorable
      hemodynamic profile, suitable for rapid control of blood pressure, clevidipine
      protects against ischemia/reperfusion injuries, which are not uncommon during
      major surgery. In anesthetized pigs, clevidipine reduced infarct size after 45
      min-long myocardial ischemia by 40%. In rats, renal function and splanchnic blood
      flow were better maintained when blood pressure was reduced with clevidipine than
      with sodium nitroprusside. Clevidipine was well tolerated in Phases I and II of
      clinical trials that included more than 300 individuals/patients. Since there are
      no known compounds with similar pharmacodynamic and pharmacokinetic properties in
      clinical development, it is anticipated that clevidipine, a compound tailored to
      the needs of anesthesiologists, has the potential to become a drug of choice for
      controlling blood pressure during surgical procedures.

PMID- 15492771
TI  - Role of hyperforin in the pharmacological activities of St. John's Wort.
AB  - The phloroglucinol derivative hyperforin has been recently shown to be a major
      antidepressant component in the extract of Hypericum perforatum. Experimental
      studies clearly demonstrated its activity in different behavioral models of
      depression. Moreover clinical studies linked the therapeutic efficacy of
      Hypericum extracts to their hyperforin content, in a dose-dependent manner. The
      molecular mechanism of action of hyperforin is still under investigation.
      Hyperforin has been shown to inhibit, like conventional antidepressants, the
      neuronal uptake of serotonin, norepinephrine and dopamine. However, hyperforin
      inhibits also the uptake of gamma-aminobutyric acid (GABA) and L-glutamate. The
      uptake inhibition by hyperforin does not involve specific binding sites at the
      transporter molecules; its mechanism of action seems to be related to sodium
      conductive pathways, leading to an elevation in intracellular Na(+)
      concentration. Other additional mechanisms of action of hyperforin, involving
      ionic conductances as well synaptosomal and vesicular function, have been
      suggested. In addition to its antidepressant activity, hyperforin has many other
      pharmacological effects in vivo (anxiolytic-like, cognition-enhancing effects)
      and in vitro (antioxidant, anticyclooxygenase-1, and anticarcinogenic effects).
      These effects could be of clinical importance. On the other hand, the role of
      hyperforin in the pharmacological interactions occurring during Hypericum extract
      therapy must be fully investigated. Hyperforin seems to be responsible for the
      induction of liver cytochrome oxidase enzymes and intestinal P-glycoprotein.
      Several pharmacokinetic studies performed in rats and humans demonstrated oral
      bioavailability of hyperforin from Hypericum extract. Only recently a new
      chromatographic method for detection of hyperforin in the brain tissue has been
      developed and validated. Taking into account the chemical instability of
      hyperforin, current efforts are directed to the synthesis of new neuroactive
      derivatives.

PMID- 15492772
TI  - Preclinical and clinical pharmacology of cyamemazine: anxiolytic effects and
      prevention of alcohol and benzodiazepine withdrawal syndrome.
AB  - Several studies have suggested that the antipsychotic compound, cyamemazine,
      possesses anxiolytic properties in humans. The original pharmacological profile
      of cyamemazine (D(2), 5-HT(2A), 5-HT(2C), and 5-HT(3) receptor antagonist), which
      was established by binding, microdialysis and behavioral studies, is consistent
      with these observations. In the light/dark exploration test, cyamemazine
      demonstrated anxiolytic-like activity by acute, but not chronic administration.
      By chronic administration, however, cyamemazine increased the time spent in the
      open arms of the elevated plus maze (EPM) test demonstrating anxiolytic-like
      activity. The discrepancy between the results obtained in these tests by acute
      and chronic administration, could be due to a combination of dopamine D(2)
      receptor antagonism with antagonism of the 5-HT(2C) and 5-HT(3) receptors. The
      action of cyamemazine on both the dopaminergic system and 5-HT(3) receptors could
      also explain the activity of cyamemazine in the management of alcohol withdrawal
      demonstrated in preclinical studies. This potential indication for cyamemazine
      and its activity in benzodiazepine withdrawal syndrome have recently been
      investigated in clinical trials and the results of these studies are presented in
      this review.

PMID- 15492773
TI  - Dihydrexidine--the first full dopamine D1 receptor agonist.
AB  - The functional role of dopamine D(1) receptors is still controversial. One reason
      for this controversy is that for a long time the only available agonists for in
      vivo characterization of dopamine D(1) receptors were benzazepines. Among them
      was the prototype dopamine D(1) receptor partial agonist, SKF 38393. The lack of
      a selective and fully efficacious dopamine D(1) receptor agonist hampered basic
      research on dopamine D(1) receptors and left the potential clinical utility of
      dopamine D(1) receptor agonists elusive. The research situation improved when the
      first potent full dopamine D(1) receptor agonist dihydrexidine, a phenanthridine,
      was introduced in the late 1980s. In contrast to SKF 38393, dihydrexidine was
      shown to stimulate cyclic AMP synthesis just as well or better than dopamine, and
      potently displaced [(3)H]SCH 23390 from rat and monkey striatal membranes. Also,
      dihydrexidine was the first dopamine D(1) receptor agonist that had potent
      antiparkinsonian activity in a primate model of Parkinson's disease. This finding
      suggested clinical utility for dopamine D(1) receptor agonists in Parkinson's
      disease and that this utility might be critically dependent on the intrinsic
      efficacy of the drug. Clinical utility for dopamine D(1) receptor agonists in
      other central nervous disorders might also be dependent on the intrinsic efficacy
      of the drug. However, even though studies with dihydrexidine as a pharmacological
      tool have pointed to the clinical use for dopamine D(1) receptor agonists,
      dihydrexidine's unfavorable pharmacokinetic profile and various adverse effects
      are likely to restrict or even preclude its use in humans. This review article
      provides an updated overview of the pharmacology of dihydrexidine and discusses
      possible clinical utility of dopamine D(1) receptor agonists in various central
      nervous system disorders.

PMID- 15492774
TI  - A review of pharmacology of NCS-382, a putative antagonist of gamma
      hydroxybutyric acid (GHB) receptor.
AB  - Gamma-hydroxybutyric acid (GHB), a naturally occurring metabolite of gamma
      aminobutyric acid (GABA), has been postulated to act as a specific agonist of GHB
      receptors and as well as a weak GABA(B) receptor agonist. To date, 6,7,8,9
      tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylideneacetic acid (NCS-382), a
      semirigid compound structurally related to GHB, is the only compound reported to
      be an antagonist of the GHB receptor sites. In this article we review the in vivo
      and in vitro pharmacological properties of NCS-382 and its interaction with GHB
      and GABA(B) receptors. Binding studies have demonstrated that NCS-382 is a
      stereoselective ligand for GHB-binding sites, with both, the high and the low
      component of population, showing the same distribution of GHB receptors. Indeed,
      this compound did not display affinity for GABA(A), GABA(B), or any other known
      receptors, while conflicting data have been reported as to its selective
      antagonist action at GHB receptor. Only a few studies have shown that NCS-382
      antagonizes GHB-induced effect, but a re-evaluation of all data reported in the
      literature suggests that the antagonistic effect of this compound could be due to
      an indirect action at GABA(B) receptors. As revealed by several behavioral
      studies, NCS-382 fails to antagonize GHB discriminative stimuli, GHB-induced
      inhibition of locomotor activity and ataxia or suppression of operant responses.
      Moreover, it is capable of either eliciting qualitatively similar effects to
      those of GHB or enhancing some actions of GHB. In addition, the NCS-382-sensitive
      electrophysiological effects of endogenous and exogenous GHB observed in vivo
      have not been completely replicated in vitro. The only electrophysiological
      action of GHB antagonized in vitro by NCS-382 required a previous blockade of
      GABA(B) receptors. We concluded that NCS-382 is a good ligand but not a selective
      antagonist for GHB receptor.

PMID- 15492775
TI  - Whole-genome analysis of temporal gene expression during foregut development.
AB  - We have investigated the cis-regulatory network that mediates temporal gene
      expression during organogenesis. Previous studies demonstrated that the organ
      selector gene pha-4/FoxA is critical to establish the onset of transcription of
      Caenorhabditis elegans foregut (pharynx) genes. Here, we discover additional cis
      regulatory elements that function in combination with PHA-4. We use a
      computational approach to identify candidate cis-regulatory sites for genes
      activated either early or late during pharyngeal development. Analysis of natural
      or synthetic promoters reveals that six of these sites function in vivo. The
      newly discovered temporal elements, together with predicted PHA-4 sites, account
      for the onset of expression of roughly half of the pharyngeal genes examined.
      Moreover, combinations of temporal elements and PHA-4 sites can be used in genome
      wide searches to predict pharyngeal genes, with more than 85% accuracy for their
      onset of expression. These findings suggest a regulatory code for temporal gene
      expression during foregut development and provide a means to predict gene
      expression patterns based solely on genomic sequence.

PMID- 15492776
TI  - BMP receptor signaling is required for postnatal maintenance of articular
      cartilage.
AB  - Articular cartilage plays an essential role in health and mobility, but is
      frequently damaged or lost in millions of people that develop arthritis. The
      molecular mechanisms that create and maintain this thin layer of cartilage that
      covers the surface of bones in joint regions are poorly understood, in part
      because tools to manipulate gene expression specifically in this tissue have not
      been available. Here we use regulatory information from the mouse Gdf5 gene (a
      bone morphogenetic protein [BMP] family member) to develop new mouse lines that
      can be used to either activate or inactivate genes specifically in developing
      joints. Expression of Cre recombinase from Gdf5 bacterial artificial chromosome
      clones leads to specific activation or inactivation of floxed target genes in
      developing joints, including early joint interzones, adult articular cartilage,
      and the joint capsule. We have used this system to test the role of BMP receptor
      signaling in joint development. Mice with null mutations in Bmpr1a are known to
      die early in embryogenesis with multiple defects. However, combining a floxed
      Bmpr1a allele with the Gdf5-Cre driver bypasses this embryonic lethality, and
      leads to birth and postnatal development of mice missing the Bmpr1a gene in
      articular regions. Most joints in the body form normally in the absence of Bmpr1a
      receptor function. However, articular cartilage within the joints gradually wears
      away in receptor-deficient mice after birth in a process resembling human
      osteoarthritis. Gdf5-Cre mice provide a general system that can be used to test
      the role of genes in articular regions. BMP receptor signaling is required not
      only for early development and creation of multiple tissues, but also for ongoing
      maintenance of articular cartilage after birth. Genetic variation in the strength
      of BMP receptor signaling may be an important risk factor in human
      osteoarthritis, and treatments that mimic or augment BMP receptor signaling
      should be investigated as a possible therapeutic strategy for maintaining the
      health of joint linings.

PMID- 15492778
TI  - Molecular basis of cellular response to cisplatin chemotherapy in non-small cell
      lung cancer (Review).
AB  - Cisplatin is one of the most potent anticancer agents, displaying significant
      clinical activity against a variety of solid tumors. For more than two decades,
      the most effective systemic chemotherapy for non-small cell lung cancer (NSCLC),
      the leading cause of cancer morbidity and mortality among men and women in the
      western world, was cisplatin-based combination treatment. Unfortunately, the
      outcome of cisplatin therapy on NSCLC seems to have reached a plateau. Therefore,
      the biological mechanisms of cisplatin action need to be understood in order to
      overcome the treatment plateau on NSCLC. Moreover, the development of resistance
      is a hurdle in the use of this drug. The molecular mechanisms that underlie this
      chemoresistance are largely unknown. Possible mechanisms of acquired resistance
      to cisplatin include reduced intracellular accumulation of cisplatin, enhanced
      drug inactivation by metallothionine and glutathione, increased repair activity
      of DNA damage, and altered expression of oncogenes and regulatory proteins. In
      addition, it is generally accepted that cytotoxicity of cisplatin is mediated
      through induction of apoptosis and arrest of cell cycle resulting from its
      interaction with DNA, such as the formation of cisplatin-DNA adducts, which
      activates multiple signaling pathways, including those involving p53, Bcl-2
      family, caspases, cyclins, CDKs, pRb, PKC, MAPK and PI3K/Akt. Increased
      expression of anti-apoptotic genes and mutations in the intrinsic apoptotic
      pathway may contribute to the inability of cells to detect DNA damage or to
      induce apoptosis. Towards an understanding of the molecular basis of the cellular
      response to cisplatin-based chemotherapy in NSCLC, in this review we provide some
      insights into the pathways involved in cisplatin damage from entering the cells
      to execution of apoptosis or survival of NSCLC cells. We believe that as more and
      more molecular mechanisms of response to cisplatin-based therapy are unraveled,
      this knowledge should provide a basis for further studies to improve our
      understanding of molecular events associated with lung NSCLC as well as to devise
      novel and effective therapeutic approaches to overcome the treatment plateau or
      reverse drug resistance in this disease.

PMID- 15492777
TI  - Dictyostelium myosin bipolar thick filament formation: importance of charge and
      specific domains of the myosin rod.
AB  - Myosin-II thick filament formation in Dictyostelium is an excellent system for
      investigating the phenomenon of self-assembly, as the myosin molecule itself
      contains all the information required to form a structure of defined size.
      Phosphorylation of only three threonine residues can dramatically change the
      assembly state of myosin-II. We show here that the C-terminal 68 kDa of the
      myosin-II tail (termed AD-Cterm) assembles in a regulated manner similar to full
      length myosin-II and forms bipolar thick filament (BTF) structures when a green
      fluorescent protein (GFP) "head" is added to the N terminus. The localization of
      this GFP-AD-Cterm to the cleavage furrow of dividing Dictyostelium cells depends
      on assembly state, similar to full-length myosin-II. This tail fragment therefore
      represents a good model system for the regulated formation and localization of
      BTFs. By reducing regulated BTF assembly to a more manageable model system, we
      were able to explore determinants of myosin-II self-assembly. Our data support a
      model in which a globular head limits the size of a BTF, and the large-scale
      charge character of the AD-Cterm region is important for BTF formation.
      Truncation analysis of AD-Cterm tail fragments shows that assembly is delicately
      balanced, resulting in assembled myosin-II molecules that are poised to
      disassemble due to the phosphorylation of only three threonines.

PMID- 15492779
TI  - Fibroblast growth factor receptor 3 protein expression in urothelial carcinoma of
      the urinary bladder, exhibiting no association with low-grade and/or non-invasive
      lesions.
AB  - Activating mutations of fibroblast growth factor receptor 3 (FGFR3), found in
      autosomal dominant human skeletal dysplasia, were reported to be involved in
      tumorigenesis and correlate with low-grade and superficial lesions of urothelial
      carcinoma. FGFR3 protein expression was immunohistochemically investigated in 126
      cases of urothelial carcinoma of the urinary bladder to evaluate the role of this
      receptor in tumor behavior. p53 expression and the proliferating activity of
      tumor cells, assessed by Ki-67 expression, were also analyzed in parallel.
      Cytoplasmic and/or membrane immunostaining for FGFR3 was observed in 62 (49.2%)
      cases, including 20 (15.9%) cases of intense staining and 42 (33.3%) of moderate
      staining. p53 expression and Ki-67 labeling index (LI) were significantly
      correlated with high tumor grade (p=0.0093 and <0.0001, respectively) and
      invasion (p=0.0041 and <0.0001, respectively). Although there were two groups of
      interesting cases: low-grade and non-invasive tumors negative for p53 but
      positive for FGFR3, and high-grade and invasive tumors positive for p53 but
      negative for FGFR3, no statistically significant relationship was found between
      FGFR3 expression and tumor grade, invasion, p53 expression or Ki-67 LI. These
      results suggest that FGFR3 protein expression in bladder cancer is unlikely to
      affect tumor behavior as a unique single factor.

PMID- 15492780
TI  - Dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine S-1 may be effective
      against peritoneal dissemination in gastric cancer.
AB  - The effects of a novel oral fluoropyrimidine derivative S-1 on peritoneal
      metastasis from gastric cancer were investigated. OCUM-2MD3 cells, a highly
      peritoneal-metastatic cell line, were injected intraperitoneally in nude mice.
      These mice were allocated to the following three groups (each group, n=10): the S
      1 group, to which 10 mg/kg body weight of S-1 was administered per os daily; the
      FT group, to which 100 mg/kg body weight of tegafur (FT) was administered per os
      daily; the control group, to which no anticancer drug was administered. Drug
      administration was starting the day after inoculation. The median survival time
      of the S-1 group was found to be significantly longer than that of the FT group
      (30 days vs. 23 days; P<0.005) and the control group (vs. 24 days; P<0.005). The
      mean values of 5-fluorouracil (5-FU) concentrations in ascites of the S-1 group
      at 1-4 h were 414-580 ng/ml (n=5), and those of FT group were 70-87 ng/ml (n=5),
      with significant differences between the two groups at each observation time. The
      high CDHP concentrations in ascites of the S-1 group were observed at 1-6 h after
      drug administration. DPD was expressed strongly in fibrous tissue around
      peritoneal metastasis and weakly in tumor cells of peritoneal metastasis
      themselves. The high concentrations and long duration of 5-FU in the peritoneal
      cavity after S-1 administration suggest that S-1 may be effective against
      peritoneal dissemination. High concentrations of CDHP may prevent 5-FU
      degradation in peritoneal dissemination and its surrounding fibrous tissue.

PMID- 15492781
TI  - Loss of estrogen receptor beta expression at cancer front correlates with tumor
      progression and poor prognosis of gallbladder cancer.
AB  - Gallbladder carcinoma is a relatively rare malignancy with an extremely poor
      patient prognosis. This malignancy occurs more frequently in women than men, yet
      expression of the estrogen receptor (ER) family has not been studied. We applied
      an immunohistochemical technique to examine the expression of ERalpha and ERbeta
      in gallbladder carcinoma tissues and then compared their expression status with
      several clinicopathological factors. We examined 26 gallbladder adenocarcinoma
      specimens and 11 non-cancerous regions using ERalpha and ERbeta antibodies.
      Expression of the ER isoforms in the cancer specimens was further evaluated at
      the central area and at the invasive front. ERbeta was expressed in most
      specimens including cancer and normal region, however ERbeta expression
      significantly differed between non-cancerous and cancerous regions. Moreover,
      negative expression of ERbeta at the invasive front was significantly associated
      with malignant properties of the primary tumor such as lymph node metastasis,
      advanced stage, lower differentiation of histologic type, lymphatic invasion and
      a poor prognosis of the patients. In conclusion, evaluation of ERbeta expression
      at cancer front may be an important factor in identifying a highly malignant
      group of gallbladder carcinoma.

PMID- 15492782
TI  - Loss of maspin expression is associated with development and progression of
      gastric carcinoma with p53 abnormality.
AB  - Maspin, a serine protease inhibitor related to the serpin family, was originally
      identified in normal mammary epithelium. Reduced expression of maspin is related
      with development, invasion and metastasis of certain human cancers. In the
      present study, the expression of maspin was examined in gastric mucosa, adenoma
      and carcinoma by immunohistochemistry and RT-PCR. In non-neoplastic mucosa,
      maspin was expressed in cytoplasm and cell membrane of foveolar epithelia, fundic
      glandular cells and pyloric glandular cells. Maspin expression was lost in 71%
      (71/100) of gastric carcinomas, and in 19% (4/21) of adenomas, respectively. Loss
      of maspin expression was significantly associated with poorly differentiated
      histology, advanced stage and deep invasion (P<0.001). There was an inverse
      correlation between maspin expression and abnormal p53 accumulation. Maspin mRNA
      expression was lost in all of 8 gastric carcinoma cell lines that was retrieved
      after treatment with demethylation agent 5-aza-2'-deoxycytidine in 5 of 8 cell
      lines. These results suggest that loss of maspin expression partly due to DNA
      methylation may participate in tumor development and progression of gastric
      carcinoma in relation with p53 pathway. Loss of maspin expression may serve as a
      biological marker of high-grade malignancy.

PMID- 15492783
TI  - Orthotopically implanted SCID mouse model of human lung cancer suitable for
      investigating metastatic potential and anticancer drug effects.
AB  - To evaluate the effects of drugs in clinical settings, an animal model of lung
      cancer similar to clinical cancer is necessary. Our previous studies described an
      SCID mouse model using orthotopic implantation of the human lung cancer cell line
      which mimicked the lymph node metastasis of patients with lung cancer. In this
      study, we made animal models that reflected various metastatic forms of lung
      cancer in humans. We applied our procedure to 6 lung cancer cell lines.
      Suspensions of 2.0 x 10(4) cancer cells were injected into the left lung of SCID
      mice. We evaluated the mRNA expressions of 52 proteins related to the metabolism
      of and resistance to anticancer drugs of each tumor cell line and its
      orthotopically implanted tumor using a customized cDNA array. Three lung cancer
      cell lines had the potential of lymphogenous metastasis and 3 cell lines had the
      potential of hematogenous metastasis in this model system. The A549 line showed
      multiple metastases, and Ma2 line showed solitary metastasis. The expression of
      52 genes in each implanted tumor was closely correlated with that in each cell
      lines (correlation coefficients: 0.8883-0.9533), and the gradient of the
      regression line was more than 0.9. This model was similar to the metastatic form
      in patients with lung cancer. The similar expression of proteins in each tumor
      cell line in vitro and implanted tumor in vivo gives an advantage in evaluating
      the effects of molecular-targeted drugs and the relationship between specific
      genes and tumor potential in preclinical studies.

PMID- 15492784
TI  - Expression of human kallikrein 7 (hK7/SCCE) and its inhibitor antileukoprotease
      (ALP/SLPI) in uterine endocervical glands and in cervical adenocarcinomas.
AB  - To investigate the potential role of human kallikrein 7 (hK7/SCCE) and its
      inhibitor antileukoprotease (ALP/SLPI) in the development and progression of
      uterine cervical adenocarcinoma, we examined hK7 and ALP protein expression by
      immunohistochemistry in 70 cervical adenocarcinomas and 13 normal cervical
      tissues. Positive hK7 expression rates in normal endocervical glands and in
      cervical adenocarcinomas were 46.2 and 80%, respectively. A significantly higher
      hK7 expression rate was observed in cervical adenocarcinomas compared to normal
      endocervical glands (p=0.0099). In contrast, positive ALP detection rates in
      normal endocervical glands and in cervical adenocarcinomas were 100 and 15.7%,
      respectively. A significantly lower ALP detection rate was observed in cervical
      adenocarcinomas compared to normal endocervical glands (p<0.0001). There was a
      significant inverse correlation between hK7 and ALP expression status (p=0.0010).
      However, no statistically significant differences in hK7 or ALP expression status
      were found with respect to age, clinical stage, histological grade and lymph node
      metastasis status in cervical adenocarcinoma cases. Log-rank testing showed that
      advanced clinical stage and positive lymph node metastasis significantly
      correlated with poor patient survival (p=0.0005 and p<0.0001, respectively),
      whereas no correlation was found between hK7 or ALP expression and survival.
      These results suggest that increased expression of hK7 and decreased expression
      of ALP might play an important role in cervical adenocarcinoma development.

PMID- 15492785
TI  - Reduced expression of endothelial and inducible nitric oxide synthase in a
      multidrug resistant variant of the MCF-7 human breast cancer cell line.
AB  - The purpose of the present study was to investigate expression of endothelial and
      inducible nitric oxide synthase in the MCF-7 human breast cancer cell line
      compared to a multidrug resistant variant, MCF-7-ADR. Immunohistochemical
      investigations demonstrated 51% of MCF-7 cells stained positive for endothelial
      nitric oxide synthase, with 46% positive for inducible nitric oxide synthase.
      However, in the breast cancer cell line that was multidrug resistant there was a
      much lower positive staining for endothelial nitric oxide synthase at 20% and for
      inducible nitric oxide synthase at 15%. For the multidrug resistant variant,
      there was also lower nitric oxide production and the band intensity for
      immunoblotting for endothelial nitric oxide synthase was weaker than for the
      parent cell line. These results lend further support to the proposal that
      expression of NOS is negatively associated with human breast cancer progression.

PMID- 15492786
TI  - Protease-activating-receptor-2 is frequently expressed in papillary
      adenocarcinoma of the gallbladder.
AB  - Gallbladder carcinoma is one of the most devastating malignant tumors in Japan.
      An important risk factor for gallbladder carcinoma is pancreaticobiliary
      maljunction (PBM), which allows reciprocal reflux of bile and pancreatic juice.
      Protease-activated-receptor-2 (PAR-2), which is activated by trypsin, may be a
      key molecule in the process of carcinogenesis in the gallbladder epithelium. We
      investigated the relation between the expression of PAR-2 and clinicopathological
      findings in gallbladder carcinoma. The study group comprised 58 patients with
      gallbladder carcinoma. PAR-2 expression was identified by immunohistochemical
      staining of all tumor specimens. PAR-2 was expressed in cancerous gallbladder
      epithelium in 37 of 58 patients (64%). PAR-2 expression occurred more frequently
      in papillary adenocarcinoma (15 of 16 patients, 94%) than in non-papillary types
      (20 of 42 patients, 48%, p=0.005). Neither lymphatic invasion (p=0.03) nor venous
      invasion (p=0.009) occurred more frequently in gallbladder carcinoma with PAR-2
      than in that without PAR-2. PAR-2 expression was not directly related to PBM
      (p=0.46). Papillary adenocarcinoma was associated with polypoid growth (p=0.01),
      PBM (p=0.01), decreased invasion to lymphatic (p=0.007) and venous vessels
      (p=0.005), lower T-factor (p<0.001), and lower clinical stage (p=0.02). PAR-2 is
      frequently expressed in papillary adenocarcinoma of the gallbladder. Trypsin may
      play an important role for carcinogenesis of the gallbladder through PAR-2
      signaling.

PMID- 15492787
TI  - Hepatocyte growth factor and c-Met immunoreactivity are associated with
      metastasis in high grade salivary gland carcinoma.
AB  - Interactions between hepatocyte growth factor (HGF) and its receptor, c-Met, have
      been associated with invasion, metastasis and carcinogenesis in in vitro
      experiments. We investigated the relationship between HGF/c-Met immunoreactivity
      and the clinical features of 33 patients with high grade salivary gland
      carcinomas. c-Met and stromal HGF (expression of HGF in fibroblasts adjacent to
      tumor nests) were found to significantly correlate with regional lymph node and
      distant metastasis (p<0.05), but not with HGF expression, in tumor cells. Stromal
      HGF was also found to correlate with tumor size (p<0.05). In addition, a
      significant correlation between c-Met and stromal HGF expression (p<0.0001) was
      observed. Overall survival in patients with c-Met and stromal HGF
      immunoreactivity was significantly worse than in patients without c-Met and
      stromal HGF immunoreactivity (p=0.0002). The present findings suggest that HGF
      may bind to c-Met in a paracrine fashion, thereby enabling metastasis of high
      grade salivary gland carcinomas. Thus, HGF/c-Met immunoreactivity might be
      associated with a poor prognosis in patients with high grade salivary gland
      carcinomas.

PMID- 15492788
TI  - Reversal of multidrug-resistance using Valspodar (PSC 833) and doxorubicin in
      osteosarcoma.
AB  - High-grade osteosarcoma is an extremely aggressive neoplasm, where over 80% of
      patients present with life-threatening micrometastases at diagnosis. Systemic
      control of the disease is therefore critical for the treatment of these patients
      and neoadjuvant chemotherapy using various drugs, including doxorubicin (DXR),
      which has been demonstrated to be the most effective regimen. Multidrug
      resistance (MDR) to some anticancer agents, including DXR, mediated by the MDR1
      gene product P-glycoprotein (Pgp), has been shown to be a major cause of
      chemotherapy failure in osteosarcoma. We analyzed the effect of a cyclosporine A
      derivate Valspodar (PSC 833) on MDR human osteosarcoma cells. We also evaluated
      Pgp expression in sporadic appendicular canine osteosarcoma. Moreover, dogs were
      treated with combined administration of DXR and PSC 833. Several blood samples
      were collected for the determination of DXR and PSC 833 levels. PSC 833 induced a
      complete reversal of the resistant phenotype at concentrations compatible with
      the clinical use. Pgp was present in 12/18 (66.6%) of the cases. At the time of
      DXR administration, adequate blood concentrations of PSC 833, to provide a
      complete MDR reversal, were obtained without clinical or laboratory findings of
      toxicity. Combination therapy with DXR and PSC 833 allowed a 30% decrease in DXR
      dose infusion with equivalent therapeutic exposure. The high incidence of Pgp
      expression in osteosarcoma confers to the study a rationale for an effective
      regimen based on down-modulation of MDR.

PMID- 15492789
TI  - Single nucleotide polymorphism in the hypoxia-inducible factor-1alpha gene in
      colorectal carcinoma.
AB  - Colorectal carcinoma is one of the most common malignancies in the world, and its
      incidence has increased in recent years. We have reported that expression of
      hypoxia-inducible factor (HIF)-1alpha correlates with expression of vascular
      endothelial growth factor (VEGF), tumor stage, lymphatic invasion, venous
      invasion, and liver metastasis. It has also been reported that a single
      nucleotide polymorphism (SNP) in exon 12 of HIF-1alpha gene is present in renal
      cell carcinoma and head and neck squamous cell carcinoma patients. We
      investigated the C1772T polymorphism in colorectal cancer patients and healthy
      control subjects to clarify the mechanism of HIF-1alpha activation in colorectal
      carcinoma. The exon 12 genotype was not associated with sex or age. The
      distribution of HIF-1alpha genotypes in controls was 89 C/C (89%), 11 C/T (11%),
      and 0 T/T (0%). The distribution of HIF-1alpha genotypes in colorectal cancer
      patients was 100 C/C (100%), 0 C/T (0%), and 0 T/T (0%). The difference in
      genotype distribution between patients and control subjects was significant
      (p<0.0005). These results suggest that the C1772T polymorphism in HIF-1alpha is
      not involved in progression or metastasis of colorectal carcinoma.

PMID- 15492790
TI  - Phosphorylation state of tumor-suppressor gene p53 product overexpressed in skin
      tumors.
AB  - Post-transcriptional modification of p53 by phosphorylation has been proposed as
      an important mechanism of p53 stabilization and functional regulation. However,
      little is known about the phosphorylation state of mutant p53 protein
      overexpressed in human tumors. We evaluated immunohistochemically the p53
      phosphorylation state of Ser392 and Ser15 sites in 44 actinic keratoses (AKs), 62
      squamous cell carcinomas (SCCs), 23 Bowen's disease (BDs) and 43 basal cell
      carcinomas (BCCs). The mean labeling index (LI) of phospho-Ser392-p53 was
      significantly higher than that of phospho-Ser15-p53 in all cases. Phospho-Ser392
      p53 protein was frequently overexpressed in not only SCCs but also AKs and BDs,
      revealing no significant difference in the immunoreactivity among them. In BCCs,
      phospho-Ser392-p53 immunoreactivity was significantly lower than that in BDs, and
      phospho-Ser15-p53 immunoreactivity was significantly lower than that in SCCs.
      Ser15 phosphorylation was significantly correlated with a high level of Ki-67 LI
      in BCCs. These results suggest that p53 overexpressed in skin tumors is more
      frequently phosphorylated at Ser392 residue than Ser15, and that the Ser392
      phosphorylation is more likely to occur early in the pathogenesis of SCC.
      Moreover, the decreased level of the phosphorylation might be characteristic of
      BCC, but the Ser15 phosphorylation seems to have an influence on BCC development.

PMID- 15492791
TI  - Humoral response to p53 is associated with conserved domains II and IV mutations
      in human colorectal cancer: a case-control study in Taiwan.
AB  - To explore the relationship between mutations of the p53 gene, p53 protein
      accumulation in tumor tissues and the presence of anti-p53 antibodies (Ab) in
      sera, a matched case-control study with 63 colorectal cancer patients positive
      for p53-Ab was carried out. These control patients were matched for age, gender,
      as well as tumor site and stage with 63 colorectal cancer patients positive for
      p53-Ab. The study was designed to analyze their p53 gene mutations in exons 4-9
      by the single strand conformation polymorphism (SSCP) followed by direct
      sequencing, as well as measuring p53 protein accumulation by
      immunohistochemistry. A significantly higher frequency of p53 mutations in exon 4
      9 and positive immunohistochemical staining of p53 protein was observed in tumors
      from p53-Ab positive patients (55.56 and 84.13%, respectively) than in tumors
      from p53-Ab negative patients (22.22 and 60.32%, respectively). Using a
      conditional logistic regression model, the humoral response to p53 was found to
      be associated with p53 gene mutation (OR = 3.34; 95% CI, 1.31-8.54, p=0.012) and
      p53 protein accumulation (OR = 3.80; 95% CI, 1.02-14.14, p=0.047). Further
      analysis showed that the frequency of p53 mutations located in the conserved
      domains II (codons 112-141) and IV (codons 234-258) was significantly higher in
      p53-Ab positive patients than in p53-Ab negative patients (50.00% (16/32) vs.
      8.33% (1/12), p=0.015, Fisher's exact test). Thus, our study demonstrated that
      the generation of p53 antibodies was usually correlated with the p53 protein
      accumulation and p53 gene mutation, especially mutations located in conserved
      domains II and IV.

PMID- 15492792
TI  - Small cell lung cancer cells express EGFR and tyrosine phosphorylation of EGFR is
      inhibited by gefitinib ("Iressa", ZD1839).
AB  - The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, gefitinib
      ("Iressa", ZD1839) has demonstrated anti-tumor activity in non-small cell lung
      cancer (NSCLC) and has been approved in over 20 countries. NSCLC has been
      reported to express high levels of EGFR. However, gefitinib appears to be more
      effective against adenocarcinoma than squamous cell carcinoma, the latter
      expressing more EGFR. In the present study, we evaluated the effect of gefitinib
      against the small cell lung cancer (SCLC) cell lines NCI-H82, NCI-H209, NCI-H510,
      NCI-H526 and NCI-H660. SCLC has been reported to express a low to undetectable
      level of EGFR. We compared the effects of gefitinib between cell lines with
      detectable and undetectable EGFR expression. First, we evaluated expression
      levels of EGFR and HER2/neu by Western blotting and immunoprecipitation
      respectively; EGFR protein was detected in two of the five SCLC cell lines,
      whereas HER2/neu was not detected in any. Next, we analyzed expression levels of
      phosphorylated ERK1/2 and compared these results with EGFR (HER-1/ErbB1) and
      HER2/neu (ErbB2) expression levels, as EGFR conducts signals through Ras-Raf-MAPK
      pathway; gefitinib inhibited phosphorylation of ERK1/2 by EGF addition in cell
      lines with detectable and undetectable EGFR expression. These data suggest that
      gefitinib is potentially effective against cancers with low EGFR expression such
      as SCLC.

PMID- 15492793
TI  - A multi-center, late phase II clinical trial of Genexol (paclitaxel) and
      cisplatin for patients with advanced gastric cancer.
AB  - Because of unsatisfactory treatment results with 5-fluorouracil-based palliative
      combination chemotherapy for advanced gastric cancer, the evaluation of new
      effective and well-tolerated regimens is needed. We conducted a multi-center,
      late phase II trial to evaluate the efficacy and safety of Genexol (a paclitaxel
      formulation) combined chemotherapy with cisplatin in patients with previously
      untreated metastatic or unresectable measurable gastric adenocarcinoma. All
      patients were between 18 and 75 years of age, with an Eastern Cooperative
      Oncology Group (ECOG) performance status of 0 to 1, and had an adequate baseline
      major organ function. Genexol 175 mg/m(2) was administered as a 3-h infusion,
      followed by cisplatin 75 mg/m(2) as an intravenous infusion day 1, once every 3
      weeks. Thirty-six patients were enrolled from 7 hospitals between November 2002
      and April 2003. Of these, 33 patients were assessable for efficacy and 35 for
      toxicity. Based on an intent-to-treat analysis, 16 patients (46%) achieved a
      partial response, 7 (20%) stable disease, and 10 (29%) progressed, giving an
      overall response rate of 46% (95% CI, 29% to 63%). The median duration of
      response was 7.1 months (95% CI, 6.3 to 7.9 months), and the median time to
      progression and overall survival were 4.9 months (95% CI, 3.2 to 6.6 months) and
      13.8 months (95% CI, 10.8 to 16.8 months), respectively. The major toxicity was
      neutropenia, with grade 3/4 intensity in 10 patients (29%). However, no febrile
      neutropenia occurred, and non-hematologic toxicity was usually mild. Grade 3/4
      toxicities included nausea (9% of the patients), vomiting (9%), peripheral
      neuropathy (9%), alopecia (9%), and myalgia (6%). In conclusion, the combination
      of Genexol and cisplatin was found to be an active and relatively well-tolerated
      regimen for the treatment of advanced gastric carcinoma.

PMID- 15492794
TI  - The effectiveness of artificial neural networks in evaluating treatment plans for
      patients requiring external beam radiotherapy.
AB  - This study was designed to determine the ability of a neural network to use data
      summarized in artificial generated dose volume histograms (DVH) for the rectum to
      evaluate and compare different patient treatment plans for the treatment of
      localized prostate cancer. One radiotherapist evaluated 250 artificially
      generated DVHs representing the distribution of a dose of ration throughout the
      rectum during external radiotherapy for patients with prostatic adenocarcinoma
      (PAC). The data were also analyzed using the Lyman NTCP-model for assessing
      complication probabilities. A neural network consisting of 10 input nodes and one
      output node was trained to categorize the plans according to the radiotherapist's
      score. The volume in each isodose was used as input, and the risk for a severe
      complication was presented as output. The classifications made by the neural
      network matched those determined by the radiotherapist and the NTCP-model. All
      three techniques showed a high correlation between each other. Artificially
      generated dose volume histograms (DVH) for the rectum can be used for training a
      neural network for scoring rectal DVHs in treatment plans for localized prostate
      cancer.

PMID- 15492795
TI  - Involvement of 90K/Mac-2 binding protein in cancer metastases by increased
      cellular adhesiveness in lung cancer.
AB  - 90K/Mac-2 Binding Protein (M2BP) plays a role in regulation of immune responses
      and cell adhesive ability in patients with cancer and infectious diseases. We
      previously reported that M2BP was highly expressed in lung cancer and that immune
      responses to M2BP were increased in many patients with lung cancer. To determine
      the involvement of M2BP in metastatic processes of cancer progression, we
      examined the ability of M2BP DNA-transduced lung carcinoma cell lines to adhere
      to extracellular matrices. Although expressions of cell-surface integrins were
      not modulated in the M2BP transfectants, they showed increased adhesiveness to
      fibronectin and collagen IV. We next analyzed the serum levels of M2BP in
      patients with lung cancer and normal donors and the relationships between M2BP
      expression and clinicopathological factors in the patients. The M2BP level was
      markedly elevated in the patients and was strongly correlated with nodal
      involvement and clinical staging. To determine whether expression of M2BP by
      cancer cells is modulated in the environment of tumor-bearing hosts, M2BP
      expression in M2BP-positive QG56 cells following exposure of the cells to pro
      inflammatory cytokines was examined. The M2BP expression in QG56 cells was up
      regulated by many of the cytokines that activate host protective immunity. The
      findings in this study suggest that M2BP plays a role in cancer metastasis by
      increased adhesiveness of cancer cells and that M2BP is increasingly produced
      even in a state of exposure to the host immune system. This molecule may be
      useful as a predictive factor of disease progression in lung cancer.

PMID- 15492796
TI  - Dietary effects of conjugated docosahexaenoic acid on N-methyl-N-nitrosourea
      induced mammary carcinogenesis in female Sprague-Dawley rats.
AB  - The dietary effects of conjugated docosahexaenoic acid (CDHA) were examined in an
      N-methyl-N-nitrosourea (MNU)-induced rat mammary carcinogenesis model. Female
      Sprague-Dawley rats were administered 50 mg/kg MNU intraperitoneally at 49 days
      of age. A powdered AIN-76A diet containing 0, 0.2 or 1.0% CDHA was fed to the
      rats from 21 to 49 days of age (before MNU; pre-initiation phase) or from 49 days
      to 40 weeks of age (after MNU; post-initiation phase). Rats were sacrificed when
      their largest mammary tumor was > or =1 cm in size or when they reached 40 weeks
      of age. All histologically detected mammary carcinomas were evaluated. In rats
      that received CDHA after MNU, development of mammary carcinoma > or =1 cm was
      inhibited, and there was a significant decrease in the final mammary cancer
      incidence and multiplicity, compared with rats that did not receive CDHA.
      Consumption of the 0.2% CDHA diet after MNU significantly prolonged latency.
      Suppression of mammary cancer yield by consumption of a CDHA diet after MNU
      administration was not dose-dependent. In rats that received CDHA before MNU,
      suppression of mammary cancer was not observed. These results indicate that CDHA
      administration in the post-initiation period suppressed mammary carcinogenesis,
      whereas CDHA administration in the pre-initiation period was ineffective.

PMID- 15492797
TI  - Aberrant methylation of p57KIP2 gene in lung and breast cancers and malignant
      mesotheliomas.
AB  - The p57KIP2 gene belongs to the Cip/Kip family of CDK inhibitors and has been
      demonstrated to be a tumor suppressor gene, being inactivated in various types of
      human cancers. We analyzed the methylation and expression status of p57KIP2 in
      lung and breast cancers, and in malignant mesotheliomas (MMs). The promoter
      region of p57KIP2 was determined by methylation-specific PCR (MSP) in samples of
      lung and breast cancer, and of MM. The expression of the gene in the cell lines
      was determined by RT-PCR and correlated with the methylation status. Aberrant
      methylation was detected by MSP in 9 of 27 (33%) and 25 of 78 (32%) lung cancer
      cell lines and tumors, respectively, 11 of 18 (61%) and 17 of 38 (45%) breast
      cancer cell lines and tumors, respectively, and 1 of 25 (4%) MM tumors. DNA
      methylation was detected but rarely in the corresponding non-malignant tissues.
      In addition, the gene expression was restored in the methylated cell lines
      following 5-aza-2'-deoxycytidine treatment, confirming that the methylation was
      indeed responsible for the gene down-regulation. We also examined the
      relationship between the p57KIP2 methylation status and the clinicopathological
      features of the primary tumors, and found that there was no relationship between
      the p57KIP2 methylation status and any of the examined clinicopathological
      features. In summary, our results demonstrate that p57KIP2 methylation associated
      with the gene down-regulation is frequently present in lung and breast cancers
      and plays an important role at the molecular level in the pathogenesis of these
      cancers.

PMID- 15492798
TI  - Epstein-Barr virus-associated gastric carcinoma in Papua New Guinea.
AB  - Using in situ hybridization assay, we examined Epstein-Barr virus (EBV) encoded
      RNA (EBER) expression in 66 cases of oral cancer, 40 esophageal cancer cases, 150
      stomach cancer cases, and 46 colorectal cancer cases diagnosed in the Pathology
      Department of Port Moresby General Hospital, University of Papua New Guinea
      during the period between 1986-2002. There were no malignancies with positive
      EBER expression except for the following two male stomach cancer cases: a male
      case with a gastric carcinoma in pylorus whose age was unknown; and a male case
      aged 55 years without information on location of tumor. Both cases were
      histologically classified as non-solid poorly differentiated adenocarcinoma of
      the Japanese histological classification. The frequency of EBV-associated gastric
      carcinomas was 1.3% (2/150), and was the lowest ever reported in the world. We
      examined genotypes of two EBV strains detected from gastric carcinomas. Four
      different regions of EBV genome were examined by PCR-RFLP, coupled with Southern
      blot hybridization. The EBV genotype of the first case were type A, wild-type F
      at BamHI-F region, type D of BamHI-I region and the kept type of the XhoI
      cleavage site in LMP1. The second case had EBV whose genotypes were type A, wild
      type F at BamHI-F region, and the kept type of the XhoI cleavage site in LMP1.
      The BamHI-I region of this case could not be analyzed.

PMID- 15492799
TI  - Infrequent somatic mutations of the ICAT gene in various human cancers with
      frequent 1p-LOH and/or abnormal nuclear accumulation of beta-catenin.
AB  - Abnormal nuclear accumulation of beta-catenin (CTNNB1) plays one of the key roles
      in the upregulation of the Wnt signalling pathway that can cause acceleration of
      cell proliferation. ICAT, inhibitor of beta-catenin and TCF4/beta-catenin
      interacting protein, was isolated and mapped to 1p36, a frequent target for LOH
      in many human cancers. We have previously observed that a number of tumors
      showing abnormal accumulation of the CTNNB1 protein do not harbor a mutation of
      the CTNNB1 gene. We studied the precise localization and genomic structure of the
      ICAT gene and analyzed its mutations in 178 human tumors developed in organs with
      frequent nuclear accumulation of the CTNNB1 protein and/or frequent LOHs of 1p36,
      but no genetic alterations were observed. Our results imply that i) genetic
      alteration of the ICAT gene does not play an important role in abnormal
      accumulation of CTNNB1 that would cause up-regulation of the Wnt signalling
      pathway, ii) mechanisms other than genetic alteration may have inactivated ICAT
      function, or iii) gene(s) on 1p36 other than ICAT may be the responsible tumor
      suppressor gene for tumors that show frequent 1p36-LOH.

PMID- 15492800
TI  - Complementation of temperature tolerance by rat Rgl-1 recessive oncogene in the
      absence of Saccharomyces cerevisiae Sop genes.
AB  - It has been demonstrated that homozygous mutations at the L(2)gl locus in
      Drosophila result in the development of tumor in the presumptive adult optic
      centers of the larval brain and of the imaginal discs. We previously cloned an
      L(2)gl homologue, Rgl-1, in the rat brain. In this study, we analyzed the
      capability of Rgl-1 in recovering temperature tolerance in the absence of
      Saccharomyces cerevisiae Sop genes, yeast homologues of the Drosophila recessive
      oncogene Lethal (2) giant larvae. The expression of Rgl-1 revealed the recovery
      of temperature tolerance at 20 degrees C in the absence of Sop genes in
      Saccharomyces cerevisiae. This indicates that the Rgl-1 cDNA we isolated from the
      rat brain is highly homologous to Lgl family members and can also substitute the
      function of Sop proteins for temperature tolerance in Saccharomyces cerevisiae.

PMID- 15492801
TI  - Breast tumour growth inhibition in vitro through the combination of
      cyclophosphamide/metotrexate/5-fluorouracil, epirubicin/cyclophosphamide,
      epirubicin/paclitaxel, and epirubicin/docetaxel with the bisphosphonates
      ibandronate and zoledronic acid.
AB  - Breast cancer has a significant capacity to metastasize to bone. Bisphosphonates
      are the standard treatment for hypocalcaemia of malignancy (HCM), which is a
      common complication of bone metastasis. The combination of bisphosphonates with
      standard anticancer drugs such as paclitaxel or tamoxifen results in a
      synergistic apoptotic effect greater than that produced by either single agent
      alone. Potential antitumour effects in vitro of the two bisphosphonates
      zoledronic acid (Zol) and ibandronate (Ib) (each at 30 microM) combined with
      different anticancer drug combinations: cyclophosphamide/metotrexate/5
      fluorouracil (CMF), epirubicin/cyclophosphamide (EC), epirubicin/paclitaxel (ET),
      and epirubicin/docetaxel (EDoc) were investigated using ATP-cell viability assay
      (ATP-CVA). Twenty cases of female primary, invasive breast cancer were assessed.
      Ibandronate and zoledronic acid alone showed an inhibitory effect on breast
      cancer tumour cells in vitro. The breast tumour growth inhibition effect for
      those two drugs amounted to 22 and 25% respectively. Inhibitory effects were
      clearly visible for all four combinations of anticancer drugs together with both
      bisphosphonates. Combinations of anticancer drugs with zoledronic acid seem to be
      more effective with respect to tumour growth inhibition than combinations with
      ibandronate.

PMID- 15492802
TI  - Impact of cytidine deaminase activity on intrinsic resistance to cytarabine in
      carcinoma cells.
AB  - Cytarabine (araC) is a highly active antimetabolite against hematological
      malignancy while the agent shows limited activity against carcinomas. In this
      study, we focused on cellular transport and catalysis of the nucleoside in order
      to elucidate the mechanism of intrinsic resistance to araC in carcinomas.
      Activities of two metabolizing enzymes for araC, deoxycytidine kinase (DCK) and
      cytidine deaminase (CDA), and cellular transport of the agent were examined in 9
      carcinoma cell lines. These variables in carcinoma lines were compared with those
      in 14 araC-sensitive leukemia lines and one leukemia line with acquired
      resistance. The mean IC50 in 9 carcinoma lines was 3 x 10(3)-fold higher than
      that in 14 leukemia lines (4.6 x 10(3) vs. 1.3 microM, p<0.01). A cell line with
      acquired resistance (U937R), which was established from U937 monocytoid leukemia
      cells, showed more than 10(3)-fold higher IC50 than the parent cells (1.6 x 10(3)
      vs. 1.3 microM). The resistance in carcinomas was associated with higher CDA
      activity and lower influx when compared to araC sensitive leukemias. Especially,
      these two types of malignant cell lines were clearly distinguished by CDA
      activity. The acquired resistance in U937R cells was followed by increase in
      cytidine deaminase (CDA) activity, decrease in DCK activity and decrease in
      influx of the drug. In conclusion, carcinomas are intrinsically resistant to
      cytarabine through high CDA activity and low cellular transport, but not low DCK
      activity. This finding suggests that treatment of carcinoma with deoxycytidine
      analogues should conquer the high CDA activity.

PMID- 15492803
TI  - Concurrent preoperative chemoradiotherapy for stage III or IV esophageal squamous
      carcinoma.
AB  - The poor progress of advanced esophageal carcinoma cannot be expected to be
      improved by surgical treatment alone. We retrospectively examined the results of
      surgery alone (SA: 39 cases) and of concurrent preoperative chemoradiation
      therapy (PCRT: 51 cases) for stage III or IV esophageal squamous carcinoma. In
      the PCRT group, the rate of pathological complete response was 31.4% for the
      primary lesion and 31.1% for metastatic lymph nodes, which viable cancer cells
      were not recognized in either region in 25.5% of all cases. In the PCRT group,
      grade 2 or more toxicity was found in 39 cases of leukopenia, 10 cases of anemia,
      7 cases of thrombocytopenia, 11 cases of esophagitis, 4 cases of stomatitis, 2
      cases of nausea, 2 cases of diarrhea, 2 cases of liver disfunction and 2 cases of
      infection. In 2 cases, PCRT was terminated for about 3 weeks because of
      thrombocytopenia. In the remaining 49 cases, PCRT was administered as scheduled.
      No statistically significant differences were noted between the PCRT group and
      the SA group in postoperative complications. There was postoperative recurrence
      in 16 cases (31.4%) in the PCRT group and 26 cases (66.7%) in the SA group
      (p=0.008). In stage III, the 5-year survival rate was 58.6% for the PCRT group
      and 17.2% for the SA group (p=0.022). In stage IV, the survival rate was 0% for
      the SA group and 16.7% for the PCRT group, showing better results in the latter,
      although there was no statistically significant difference. Multivariate analysis
      of prognostic variables revealed that therapeutic method (presence or absence of
      PCRT) contributed the greatest to the prognosis. These results indicate that PCRT
      is an effective adjuvant therapy for squamous cell carcinoma.

PMID- 15492804
TI  - Predicting recurrence and metastasis of stage II/Dukes' B colorectal cancer
      without lymph node metastasis.
AB  - This study was designed to compare the prediction of recurrence based on
      detection of occult neoplastic cells (ONCs) in lymph nodes or by using high-risk
      criteria for recurrence/metastasis in patients with Dukes' B colorectal cancer.
      Prediction of recurrence based on the detection of ONCs had a sensitivity of
      59.1% (13/22), a false-positive rate of 7.8% (8/102), a specificity of 92.2%
      (94/102), and a negative predictive value (NPV) of 91.3% (94/103). Prediction of
      recurrence based on positivity for at least 2 of the 3 high-risk criteria had a
      sensitivity of 90.9% (20/22), a false-positive rate of 49.0% (50/102), a
      specificity of 51.0% (52/102), and an NPV of 96.3% (52/54). Among the 21 patients
      in whom ONCs were detected, prediction of recurrence based on the presence of all
      3 high-risk criteria including ONCs had a sensitivity of 84.6% (11/13) and a
      positive predictive value (PPV) of 78.6% (11/14). These results suggest that
      colorectal cancer is unlikely to recur in patients without ONCs, while recurrence
      is likely in patients who fulfill 2 or more of the high-risk criteria.
      Accordingly, a combination of these parameters may be useful for the early
      prediction of recurrence/metastasis to assist in the choice of postoperative
      systemic chemotherapy.

PMID- 15492805
TI  - Deregulation of p73 isoform equilibrium in benign prostate hyperplasia and
      prostate cancer.
AB  - p73, a p53 homologue important for growth suppression, differentiation and
      induction of apoptosis, utilizes different promoters and undergoes alternative
      splicing to produce several isoforms differing in their ability to overlap p53
      functions. Using reverse transcriptase-polymerase chain reaction (RT-PCR) to
      assess the mRNA levels of p53, p73 (total and isoforms specific for exons 2 and
      13), MDM2, CDKN1A and beta2-microglobulin as internal control, we analyzed 35
      prostate carcinomas and 44 benign prostate hyperplasias (BPH) compared to 14
      normal prostates. Shift of p73 isoform mRNA levels from exon 13 lacking to exon
      13 containing copies was observed in 80% of prostate cancer cases and in 52.3% of
      BPH specimens, and from exon 2 containing to exon 2 lacking (p73Deltaexon2)
      transcripts in 45.7% of cancer cases, but only in 9.1% of BPH samples. From these
      findings we deduce that p73 isoform balance is disrupted in prostate cancer and
      BPH, suggesting that this disequilibrium could play an important role in both
      prostate hyperplasia and malignancy.

PMID- 15492806
TI  - Adenosine triphosphate (ATP) enhances the antitumor effect of etoposide (VP16) in
      lung cancer cells.
AB  - We have previously reported that adenosine triphosphate (ATP) enhances the
      cytotoxic effects of 4-hydroperoxycyclophosphamide (4HC) on leukemia cells
      without affecting the normal hematopoietic stem cells. Increased cell membrane
      permeability induced by ATP may cause high incorporation of 4HC into leukemia
      cells, ultimately leading to cell death. In the present study, we show that ATP
      has cytotoxicity against PC14, a lung adenocarcinoma cell line. When PC14 cells
      were cultured with 1, 3, and 5 mM ATP, colony number significantly decreased to
      91.0, 48.8, and 2.3% respectively, compared to untreated controls. Additionally,
      ATP enhanced the antitumor effects of etoposide (VP16) in PC14 and another lung
      adenocarcinoma cell line, A549. With 5, 25, and 50 mM VP16, the percentage of
      colony numbers compared to control was 95.5, 75.8, and 61.3% in PC14 and 86.0,
      65.0, and 57.1% in A549 cells, respectively. In the presence of 3 mM ATP,
      however, the colony number of PC14 was further limited to 49.6, 34.1, and 24.4%
      of the untreated level in 5, 25, and 50 mM VP16, respectively. When A549 cells
      were incubated with 1 mM ATP, the proportion of clonogeneic cells significantly
      fell to 62.5, 41.7, and 31.7% in 5, 25, and 50 mM VP16, respectively. With 3 and
      5 mM of ATP, uptake of [3H]VP16 in PC14 cells increased respectively to 8.9- and
      14.1-fold of the negative controls. These results suggest that ATP itself has
      antitumor effects on lung cancer cells and enhances the cytotoxicity of VP16
      through the increased uptake of VP16 into the cells. The combined use of ATP and
      antitumor agents such as VP16 may have the potential to improve the therapeutic
      index in human lung carcinoma.

PMID- 15492807
TI  - Prognostic value of cell cycle regulator molecules in surgically resected stage I
      and II breast cancer.
AB  - Success in breast cancer treatment depends greatly upon early detection, and in
      the employment of prognostic markers able to anticipate the evolution of the
      disease, allowing a more rational management of the patient. A fundamental cause
      of cancer is the alteration of the genetic material, which may modify the
      expression of proteins that play key roles in cell cycle progression. The aim of
      this study was to analyze the expression of cyclins D1, E, and B1 and of the
      CDKIs p16 and p21 in a population of uniformly treated patients with stage I or
      II breast tumors (n=56) compared with patients with benign breast pathology
      (n=23). Malignant breast tumors showed higher cyclin E and lower p21 expression
      than benign breast pathology (NS), determined by immunohistochemistry (IHC). In
      breast cancer patients, overexpression of cyclins D1 and E was associated with
      the presence of ER and stage respectively independently of other prognostic
      variables (multivariate analysis). Kaplan-Meier curves demonstrated that only
      overexpression of cyclin E was associated with a longer recurrence-free survival.
      Cox analysis showed that neither cyclins nor CDKIs were independent prognostic
      markers. We demonstrated that several regulators of cell cycle progression were
      altered in a large number of breast tumor cases, however, these abnormalities
      were not indicators of a worse outcome in breast cancer patients of stages I and
      II.

PMID- 15492808
TI  - Ubiquilin-1 is a novel HASH-1-complexing protein that regulates levels of
      neuronal bHLH transcription factors in human neuroblastoma cells.
AB  - The basic helix-loop-helix (bHLH) transcription factor mammalian achaete-scute
      homologue-1 (MASH-1 in mouse and HASH-1 in humans) is expressed in specific
      subsets of embryonic neuronal precursors of both the peripheral and central
      nervous systems. This gene is essential for development of olfactory and most
      peripheral autonomic neurons. Neuro-blastoma is a pediatric malignancy derived
      from sympathetic nervous system precursors and HASH-1 is expressed in a majority
      of neuroblastoma tumors and cell lines, indicating the immature phenotype of
      these cells. Using a human neuroblastoma cDNA library and the yeast two-hybrid
      system to identify novel HASH-1-interacting proteins, we isolated ubiquilin-1
      (DA41, hPLIC-1), a gene that contains multiple ubiquitin-related domains. Further
      analyses showed that ubiquilin-1 interacts not only with HASH-1, but also with
      other tissue-specific bHLH proteins, including HES-1. Overexpression of ubiquilin
      1 led to accumulation of HASH-1 and HES-1. Moreover, ubiquilin-1 was translocated
      from the cytoplasm to the nucleus upon co-expression with HASH-1. These results
      indicate that ubiquilin-1 plays an active role in the precise regulation of HASH
      1 and of other tissue-specific bHLH proteins.

PMID- 15492809
TI  - The ectopeptidases CD10, CD13, CD26, and CD143 are upregulated in gastric cancer.
AB  - Due to their extracellular orientation, the ectopeptidases CD10, CD13, CD26, and
      CD143 have numerous functions, including the post-secretory processing of the
      neuropeptides and peptide hormones involved in the regulation of growth and
      differentiation in the gastrointestinal tract. We investigated the transcription
      and expression pattern of these four ectopeptidases in gastric carcinomas (GC),
      the corresponding non-neoplastic epithelium, a selection of lymph node metastases
      (LNM), and the MKN28, AGS, NCI-N87, KATO III gastric cancer cell lines. The
      gastric foveolar epithelium did not express CD10, CD13, or CD143, but the
      intestinal metaplasia demonstrated strong immunoreactivity at the brush border
      for all four ectopeptidases. CD10, CD13, and CD143 were significantly up
      regulated in GCs and the lymph node metastases, confirming that they are
      important for the tumor cell biology. However, there is a lack of correlation
      between expression in intestinal metaplasia and tumor, as well as in tumor and
      LNM. Cell proliferation assays were performed with MKN28 and AGS, in which
      inhibition of CD10 significantly reduced the growth of both cell lines, and
      inhibition of CD13 significantly increased the proliferation of the AGS cells,
      indicating that the ability to degrade gastrointestinal peptides may play an
      important role in the pathobiology of gastric cancer.

PMID- 15492810
TI  - Detection of S100B, S100A6 and galectin-3 ligands in meningiomas as markers of
      aggressiveness.
AB  - The biological factors responsible for the increased aggressiveness in atypical
      meningiomas are not well known. The aim of this study is to evaluate the
      discriminatory value of a number of biological markers (S100 proteins and
      galectin-3 and its ligand profile) with respect to benign and atypical
      meningiomas. Using 63 meningiomas (39 benign and 24 atypical), we performed a
      semi-quantitative histochemical analysis of both the expression of galectin-3 and
      its ligand profile and the Ca2+-binding proteins S100A5, S100A6 and S100B. Three
      features were considered for each marker, namely the labeling index (LI), the
      staining intensity (SI) and the global score (LI + SI). A low S100A6 labeling
      index was observed in 51% of the benign and 25% of the atypical meningiomas
      (P=0.035). Furthermore, high S100B scores were observed in 46% of the benign and
      in only 8% of the atypical meningiomas (P=0.001). Seventy-one percent of the
      atypical meningiomas exhibited a low level of staining intensity for the galectin
      3-binding sites as compared to only 36% of the benign meningiomas (P=0.007). The
      combination of these three markers (by means of a decision tree) enabled an
      improved discriminatory criterion to be established between the benign and the
      atypical meningiomas. Our results thus suggest that the galectin-3-binding sites
      and S100B (and S100A6 to a lesser extent) could play a role in the aggressiveness
      characterizing atypical meningiomas.

PMID- 15492811
TI  - Expression of p27 and MAPK proteins involved in all-trans retinoic acid-induced
      apoptosis and cell cycle arrest in matched primary and metastatic melanoma cells.
AB  - We investigated whether p27 and mitogen-activated protein kinase (MAPK) proteins
      were involved in all-trans retinoic acid (atRA)-induced apoptosis and cell cycle
      arrest. Matched primary and metastatic melanoma cells were exposed to atRA.
      Apoptosis and cell cycle were detected by flow cytometry. Expression of p27, Ras,
      B-raf, Mek and Erk proteins was examined. Results showed that atRA induced
      apoptosis and cell cycle arrest in both primary and metastatic melanoma cells.
      The primary melanoma cells were more vulnerable than their matched metastatic
      cells. Expression of p27 was increased, while MAPK proteins were decreased, this
      response was dose- and time-dependent. Alterations of these proteins were more
      pronounced in primary melanoma cells than in the matched metastases. These data
      indicate that up-regulation of p27 and down-regulation of MAPK proteins were
      involved in atRA-induced apoptosis and cell cycle arrest in melanoma.

PMID- 15492812
TI  - The PDZ protein Tip-1 is a gain of function target of the HPV16 E6 oncoprotein.
AB  - Previous work has indicated that the PDZ domain Tax interacting protein 1 (Tip-1)
      is a target of the HTLV1 Tax protein and is a potential RhoA effector. We have
      used the yeast two-hybrid system to show that Tip-1 also interacts with the HPV16
      E6 protein. This interaction was confirmed by co-immunoprecipitation from E6
      expressing C33A cervical carcinoma cells (C33A-E6) which showed that Tip-1 was
      not degraded by interaction with the HPV16 E6 oncoprotein. During routine passage
      we observed that C33A-E6 had a less compact morphology and were less adherent
      than control vector transfected cells C33A-V cells - a known effect of GTP-RhoA.
      Comparison of C33A-E6 to C33A-V demonstrated that E6 expressing cells had higher
      levels of phosphorylated myosin light chains (MLC) and increased cell motility,
      which was inhibited by antisense silencing of Tip-1 expression and by the RhoA
      kinase (ROCK) inhibitor Y27632. Both C33A-E6 and C33A-V cells were shown to
      express GTP activated RhoA. Since ROCKs can be activated by GTP RhoA these data
      indicate that E6 may increase cell motility by augmenting GTP RhoA mediated
      activation of ROCKs and that this is dependent on the expression of the Tip-1
      protein.

PMID- 15492813
TI  - Subcellular localization of MUC1 recognized by a monoclonal antibody MY.1E12
      correlates with postsurgical prognosis in differentiated-type gastric carcinomas
      of stage II and III.
AB  - Because of the complex nature of the diverse histologic grade in gastric
      carcinomas a useful biomarker should be provided to scale the aggressiveness of
      the disease and to determine surgical strategy, especially for advanced
      carcinomas. Our previous study of MUC1 in gallbladder carcinoma using mAb MY.1E12
      has revealed the stromal localization of MUC1 adjacent to the carcinoma was
      correlated with poor prognosis. In gastric carcinoma the biological significance
      of the localization of MUC1 recognized by mAb MY.1E12 has not been fully
      investigated. We performed immunohistochemical analysis to determine the
      correlations with the localization of mAb MY.1E12-reactive-MUC1 (MY.1E12-MUC1)
      and clinicopathological findings. A total of 91 consecutive patients with stage
      II, IIIA or IIIB gastric carcinoma after curative resection were reviewed
      retrospectively. The localization of MY.1E12-MUC1 was classified as negative,
      apical, cytoplasmic or stromal type based on the predominant subcellular
      localization. Immunostaining of MY.1E12-MUC1 was recognized in 84% of the 55
      cases of differentiated-type carcinoma and in 53% of the 36 cases of
      undifferentiated-type carcinoma (P<0.01). In differentiated-type carcinoma, the
      proportion of stromal-type dominant localization of MY.1E12-MUC1 was increased at
      the deepest invading sites. Postsurgical liver metastasis was seen in 11 (30%) of
      37 cases showing stromal or cytoplasmic-type localization-dominant group and in 1
      (6%) of 18 cases showing apical-type localization-dominant group or negative
      staining group (P<0.05). The postsurgical survival was significantly poorer in
      the former group than in the latter (P=0.004). In differentiated-type gastric
      carcinoma, the presence of the cytoplasmic- or stromal-type localization of
      MY.1E12-MUC1 at the deepest invading sites correlates with aggressiveness of the
      disease, such as the tendency to form liver metastasis. This phenotype may serve
      as a unique biological feature associated with the malignant behavior of
      differentiated-type gastric carcinomas.

PMID- 15492814
TI  - Anti-endostatin monoclonal antibody enhances growth of human hepatocellular
      carcinoma cells by inhibiting activity of endostatin secreted by the transplanted
      cells in nude mice.
AB  - Endostatin, a fragment of collagen XVIII, inhibits angiogenesis in tumors, and is
      expected to become a new anticancer drug. However, its effectiveness is still
      controversial, because some researchers failed to reproduce the same marked
      regression of tumors by the peptide. We gave anti-endostatin monoclonal antibody,
      designated as CH18B, to nude mice transplanted with human hepatocellular
      carcinoma cells (JHH-1 line) that endogenously produced endostatin from collagen
      XVIII secreted by the cells themselves. As a result, CH18B promoted tumor
      angiogenesis by inhibiting endostatin activity in the tumor and subsequently
      increased tumor mass by preventing cancer cells from undergoing apoptosis. But
      the antibody itself did not stimulate proliferation of the tumor cells. Our
      present experimental procedure, the use of anti-endostatin antibody, definitely
      solved the question whether endostatin might exert its anticancer activity.

PMID- 15492815
TI  - Allele-specific methylation analysis on upstream promoter region of H19 by
      methylation-specific PCR with confronting two-pair primers.
AB  - H19 and IGF2 genes are imprinted genes and expressed differently depending on
      whether they are carried by a chromosome of maternal or paternal origin; H19 is
      expressed only from the maternal allele and IGF2 only from the paternally
      inherited allele. The upstream promoter region of H19 has the imprinting-control
      region (ICR) or CTCF binding sites, where the methylation status of this region
      is critical to the regulation of imprinting of the H19/IGF2 locus located in
      chromosome 11p15. There are various reports on imprinting disorders in this
      region. In colorectal cancer aberrant biallelic methylation of CTCF binding site
      has been reported, and aberrant hypomethylation of this region in bladder cancer.
      Thus, certain human neoplasms have either hyper- or hypo-methylation in the ICR.
      Hence it is still difficult to analyze allele-specific methylation disorder of
      the region, or differentially methylated regions (DMR), locate upstream of H19.
      Here we report a new method, which could distinguish paternal epigenetic or
      maternal epigenetic pattern by a single PCR assay, to combine methylation
      specific PCR and PCR with confronting two-pair primers (MSP-CTPP). Using this
      method, we investigated the region close to H19 ICR in 161 colorectal cancer and
      65 gastric cancer cases.

PMID- 15492816
TI  - Genes associated with human hepatocellular carcinoma cell chemosensitivity to 5
      fluorouracil plus interferon-alpha combination chemotherapy.
AB  - Recently, combined chemotherapy with 5-fluorouracil (5-FU) and interferon (IFN)
      alpha has been reported to show marked effects in patients with advanced
      hepatocellular carcinoma. We investigated the genes associated with
      susceptibility to this combination therapy. The gene expression profiles of eight
      human hepatocellular carcinoma cells (HepG2, Hep3B, Huh7, Huh6, PLC/PRF/5, HLE,
      HLF, and SK-Hep1) were evaluated using an oligonucleotide microarray that
      consisted of 3,800 genes. The 50% growth inhibitory concentration (GI50) values
      for 5-FU, IFN-alpha, and the combination of 5-FU plus IFN-alpha were determined
      by the MTT assay. We selected genes that were expressed differentially between
      the cells with increased susceptibility to the combination therapy and the
      remaining cells. Relevance networks of the gene expression patterns and GI50
      values of the susceptible cells were constructed to find genes associated with
      susceptibility to the combination therapy. Of the eight cells tested, five showed
      increased susceptibility to 5-FU plus IFN-alpha compared with 5-FU treatment
      alone. Among the 3,800 genes, 25 were expressed differentially between
      susceptible cells and resistant cells. The relevance networks revealed that
      sensitivity to 5-FU plus IFN-alpha involved the expression of 27 independent
      genes, which included 10 genes that are commonly associated with sensitivity to 5
      FU alone. We selected a set of genes to predict susceptibility to 5-FU plus IFN
      alpha combination therapy. We also selected genes that play key roles in the
      synergistic effect of this combination therapy. These gene sets should prove
      useful in evaluations of the efficacy and underlying molecular mechanisms of this
      combination therapy.

PMID- 15492817
TI  - Inhibition of human hepatocellular carcinoma by L-proline-m-bis (2-chloroethyl)
      amino-L-phenylalanyl-L-norvaline ethyl ester hydrochloride (MF13) in vitro and in
      vivo.
AB  - A new anticancer tripeptide, L-proline-m-bis (2-chloroethyl) amino-L-phenylalanyl
      L-norvaline ethyl ester hydrochloride (MF13), was investigated for its activity
      and mechanism in human hepatocellular carcinoma (HCC) cell lines. MF13 showed
      antiproliferative activities in the panel of 7 human HCC cell lines with IC50 in
      the range of 0.08-2.32 microM. A significant blockade in the S-phase occurred in
      tumor cells 12 h after their exposure to MF13. The inactivated Rb (phosphorylated
      Rb, pRb), which is present in the S-phase, was increased within 6 h of treatment.
      Bcl-2 expression was without change in hepatocarcinoma cells treated with MF13;
      however, a significant increase of bax was observed, resulting in a decreased
      ratio of bcl-2/bax. Increased activity of caspase-9, -8 and -3 was detected in
      the MF13 treated cells, indicating an activated pathway of apoptosis by MF13.
      Morphological examination as well as DNA gel electrophoresis demonstrated a
      nuclear fragmentation and DNA degradation in the form of multiple-unit DNA ladder
      in MF13 treated tumor cells. MF13 alone at 10 mg/kg (i.p.) inhibited HepG2 tumor
      in nude mice by more than 94% in volume. Bel-7402 tumor originated from a Chinese
      patient with HCC exhibited a sensitivity to MF13 similar to HepG2 in vivo.
      Antitumor effect of MF13 in the nude mice bearing human hepatocarcinoma (Bel-7402
      or HepG2) was stronger than mitomycin C as well as its precursor m-sarcolysin
      (p<0.01), and comparable with cyclophosphamide. We believe MF13 merits
      consideration for further investigation as an agent against human hepatocellular
      carcinoma.

PMID- 15492818
TI  - Mutations in the N-terminal domain of DFF45 in a primary germ cell tumor and in
      neuroblastoma tumors.
AB  - DFF45 has essential functions in the final stage of apoptosis by acting both as a
      folding chaperone and a DNase inhibitor of DFF40. The gene encoding DFF45 (DFFA)
      maps to the consensus deleted region in primary neuroblastoma (NB; 1p36.2-3) and
      within the homozygously deleted region in an NB cell line (1p36.2). DFF45 is
      therefore an attractive candidate NB tumor suppressor. In a previous study we
      found a rare allele variant, causing a non-polar to a polar amino acid exchange
      (Ile69Thr) in a preserved hydrophobic patch of DFF45, and we also found DFFA to
      be preferentially expressed in favorable NB tumors. We have extended the previous
      study and performed mutation analyses in another 56 NB tumors (100 in total) as
      well as a set of other tumors for coding mutations in DFFA. We have also
      performed studies of the DFFA expression in tumors using real-time PCR. We found
      a missense mutation (Ile15Met) in the remaining allele of a teratoma with
      heterozygous deletion of 1p, and a three base-pair deletion in an NB of unknown
      stage causing a deletion of amino acid 37 in DFF45. The one-base substitution
      detected in the teratoma was not present in the patients constitutional DNA, i.e.
      it is a true mutation present in the tumor DNA only. In conclusion, three
      different coding alterations have been found in the region encoding the N
      terminal regulatory domain of DFF45, responsible for binding and achieving its
      chaperone and inhibitor functions on other proteins. Moreover, by real-time RT
      PCR expression study, we found the mRNA level of DFFA to be significantly
      (p=0.038) reduced by a factor of 1.7 times in NB tumors of unfavorable outcome.

PMID- 15492819
TI  - Relationship between activation of epidermal growth factor receptor and cell
      dissociation in pancreatic cancer.
AB  - In our previous investigations, mitogen-activated protein kinase kinase 2
      (MEK2)/extracellular signal-regulated kinase 2 (ERK2) signaling pathway was found
      to be correlated with the cell dissociation induced by dissociation factor (DF)
      in pancreatic cancer cells. In this study, the expressions of epidermal growth
      factor receptor (EGFR), phosphorylated EGFR (p-EGFR), and its downstream kinases
      MEK1/2 and ERK1/2, were analyzed to clarify the regulatory mechanism of cell
      dissociation in pancreatic cancer cells. Two hamster (PC-1.0 and PC-1) and two
      human (AsPC-1 and Capan-2) pancreatic cancer cell lines were used.
      Immunocytochemical study was performed using anti-EGFR, p-EGFR, phosphorylated
      MEK1/2 (p-MEK1/2), and phosphorylated ERK1/2 (p-ERK1/2) antibodies. DF-treatment
      markedly induced the expressions of EGFR, p-EGFR, p-MEK1/2, p-ERK1/2, as well as
      the dissociation of cell colonies in PC-1 and Capan-2 cells. In contrast, AG1478
      (an EGFR inhibitor) treatment significantly induced the cell aggregation in PC
      1.0 and AsPC-1 cells which usually grew as single cells, but strongly suppressed
      the expressions of EGFR, p-EGFR, p-MEK1/2, and p-ERK1/2. These observations
      demonstrate that activation of EGFR is closely involved in cell dissociation in
      pancreatic cancer through activating MEK/ERK signaling pathway.

PMID- 15492820
TI  - Schedule-dependent synergism of vinorelbine and 5-fluorouracil/UFT against non
      small cell lung cancer.
AB  - Elderly patients with advanced non-small cell lung cancer (NSCLC) require
      chemotherapy that is effective and minimally toxic. We evaluated the activity of
      a combination of vinorelbine and 5-fluorouracil (5-FU)/UFT (a fixed combination
      of tegafur and uracil) in vitro and in vivo to establish a rationale for clinical
      use. The cytotoxic activities of various combinations of vinorelbine and 5-FU,
      the active metabolite of tegafur, were analyzed by a 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazlium bromide (MTT) assay and isobologram technique in vitro,
      using 3 NSCLC cell lines (A549, PC14, and Ma10). Sequential exposure to
      vinorelbine followed by 5-FU showed additive or synergistic activity against all
      3 NSCLC cell lines tested. The reverse sequence showed no synergism. Antitumor
      activity and survival prolongation after treatment with different combinations of
      vinorelbine and UFT were evaluated in nude mice bearing PC14 xenografts.
      Treatment with vinorelbine before UFT was associated with higher antitumor
      activity, less toxicity, and longer survival than the reverse sequence. To
      clarify the underlying mechanism by which the combination exerts the synergistic
      effects, the expression of thymidylate synthase (TS) was assessed by Western blot
      analysis in vitro and by immunohistochemical analysis in an animal model.
      Vinorelbine suppressed the 5-FU-induced increase in TS protein in A549 cells. In
      PC14 tumor tissues of animal models, TS expression in cancer cells was suppressed
      by vinorelbine. Our data suggest that treatment with vinorelbine injection before
      oral UFT may have synergistic activity against NSCLC. This synergistic activity
      may be attributed to increased chemosensitivity to UFT caused by vinorelbine
      induced suppression of TS.

PMID- 15492821
TI  - CD80 gene therapy for lymph node involvement by gastric carcinoma.
AB  - The co-stimulatory molecule, CD80 (B7-1), is a ligand of CD28 and plays a key
      role in the induction of cell-mediated immune responses. Many tumors, including
      gastric cancer, have decreased expression of CD80 which leads to a failure of
      immune recognition. Lymph node spread is a factor of poor prognosis in gastric
      cancer. In this study, we transfected the CD80 gene by an adenovirus vector into
      a human gastric cancer cell line, OCUM-2MLN, and analyzed the effect on lymph
      node disease in vitro and in vivo. After transfection of CD80 in vitro, the
      adhesive ability of cancer cells for peripheral blood mononuclear cells and their
      cytotoxicity showed significant regression (p<0.01). Intratumoral injection of
      AdCD80 caused significantly growth of subcutaneous tumors. In vivo lymph node
      spread was suppressed by injection of AdCD80 into gastric tumors. Histopathologic
      findings revealed CD80-positive cells around the tumor. These results suggest
      that CD80 gene transfer into cancer cells using an adenovirus vector might be a
      promising approach for in vivo cancer therapy.

PMID- 15492822
TI  - Influence of IGF-IR stimulation or blockade on proliferation of human renal cell
      carcinoma cell lines.
AB  - Several tumors secrete insulin-like growth factors (IGFs) for autocrine growth
      stimulation and protection from apoptosis. However, the mechanisms responsible
      for tumor growth in renal cell carcinoma (RCC) are unclear. In this study the
      biological role of exogenous IGFs in two malignant RCC cells (Caki-2 and SK-RC
      52) were investigated in vitro, and compared to the breast cancer cell line MCF
      7. IGFs but not the related epidermal growth factor stimulated both RCC cell
      lines. Caki-2 expressed higher levels of IGF-IR and proliferated more vigorously
      to added IGF-I, IGF-I analogues des(1-3)IGF-I, LongR3IGF-I and IGF-II compared to
      SK-RC-52. Neutralizing IGF-IR antibodies reduced the IGF driven proliferation in
      both cell lines. Interestingly, soluble IGF-I receptor resulted in strong growth
      inhibition of SK-RC-52, while no marked effect on Caki-2 was observed. Moreover,
      Caki-2 expressed a broad panel of IGFBPs, while SK-RC-52 more selectively
      secreted high levels of IGFBP-3. Exogenous IGFBP-3 strongly inhibited IGF-I
      driven proliferation in SK-RC-52, but worked in synergy with IGF-I in Caki-2.
      Both the IGF-IR and IGFBP-3 were present in respectively 4/4 and 4/8 human
      malignant renal tissues. In light of this and with the functional data presented
      in this study, interference with this growth factor system may provide a novel
      therapeutic approach in renal cancer therapy.

PMID- 15492823
TI  - Expression of Wnt genes and frizzled 1 and 2 receptors in normal breast
      epithelium and infiltrating breast carcinoma.
AB  - The Wnt genes encode a family of related, secreted proteins which initiate a
      signal cascade upon binding to cell surface receptor molecules. The signaling
      pathway has been shown to be critical for normal growth and development in model
      organisms and is implicated in the genesis of numerous human cancers. Wnt
      proteins regulate mammary development in the mouse but their precise role in
      normal breast development and malignant transformation in humans remains poorly
      defined. In this study, we have examined the expression of several Wnt ligands by
      in situ anti-sense RNA hybridization in normal and malignant human breast tissue,
      as well as in several estrogen-responsive and estrogen-independent human breast
      cancer cell lines. The specific Wnt genes tested included Wnt1, Wnt2, Wnt4,
      Wnt5a, Wnt5b, Wnt6, Wnt7b and Wnt10b. We have also studied the expression of
      frizzled receptors 1 and 2 by immunohistochemistry in these tissues. Our results
      indicate that several of the Wnt ligands, especially Wnt1 and Wnt6, are strongly
      expressed in both normal and malignant breast tissue and that Wnt7b is down
      regulated in breast cancer, compared to normal breast epithelium. The expression
      of frizzled 1 and 2 receptors was found to be up-regulated in breast cancer.
      These studies provide additional support to the hypothesis that the Wnt signaling
      pathway is involved in human breast cancer.

PMID- 15492824
TI  - A novel oncoprotein RNF43 functions in an autocrine manner in colorectal cancer.
AB  - We previously analyzed expression profiles of 20 colorectal tumors by means of
      genome-wide cDNA microarray. Among the genes that were commonly up-regulated in
      the CRCs, we further characterized biological importance of a novel human gene
      termed RNF43 (RING finger protein 43) in colorectal carcinogenesis. Multiple
      tissue northern blot analysis revealed undetectable expression of RNF43 in normal
      adult tissues examined and low levels of expression in fetal kidney and lung. Its
      exogenous expression conferred a growth-promoting effect in COS7 and NIH3T3
      cells, and suppression of its expression by specific short interfering RNAs
      retarded the growth of colon cancer cells. Interestingly, RNF43 protein was shown
      to be a secreted protein, and addition of the conditioned media of the RNF43
      transfected cells into culture media of NIH3T3 cells revealed a significant
      enhancement of cell growth. These data suggest that RNF43 may exert its growth
      promoting effect in an antocrine manner, and that it may be a novel diagnostic
      marker for colorectal cancer.

PMID- 15492825
TI  - Abnormal expression of cell cycle regulators in FUS-CHOP carrying liposarcomas.
AB  - Myxoid/round cell liposarcomas (MLS/RCLS) are characterized by chromosome
      translocations that result in formation of FUS-CHOP or EWSR1-CHOP fusion
      oncogenes. More than 95% of the tumors carry one of these fusion genes. FUS-CHOP
      transforms 3T3 cells and causes MLS/RCLS-like tumors in transgenic mice. The
      fusion oncoproteins act as abnormal transcription factors and are believed to
      induce abnormal expression of growth controlling genes as part of their
      transforming activities. The aim of this study was to search for recurrent
      abnormal expression patterns of cell cycle regulating proteins and growth factor
      receptors. A series of 14 MLS/RCLS, 2 MLS/RCLS derived cell lines and a FUS-CHOP
      transfected human sarcoma cell line were analyzed using immunohistochemistry,
      Western blotting, and cDNA microarray based screening. The results revealed a
      highly abnormal expression pattern of several growth controlling proteins. The G1
      cyclins D1 and E and their associated kinases CDK4 and CDK2 were strongly
      overexpressed in all of the tumors. High expression levels were also found for
      Cdk4/6 inhibitor P16 and CDK2 inhibitors P27 and P57. The growth factor tyrosine
      kinase receptors PDGFRB and EGFR were present in most cells of all investigated
      tumors. We conclude that deregulation of G1 controlling proteins is common in
      MLS/RCLS and that aberrant expression of these proteins is of importance in the
      pathogenesis of this tumor type.

PMID- 15492826
TI  - Genetic alterations in doxorubicin-resistant hepatocellular carcinoma cells: a
      combined study of spectral karyotyping, positional expression profiling and
      candidate genes.
AB  - Despite a prolongation of patient survival, the overall response of doxorubicin
      (DX) treatment on patients with hepatocellular carcinoma (HCC) remains modest.
      This is largely attributed to the development of tumor drug resistance either at
      the onset or during the course of treatment. To investigate the genetic changes
      associated with DX chemo-resistance, we examined the cytotoxic effect of DX on a
      panel of 9 HCC cell lines (HepG2, Hep3B, PLC/PRF/5, and six in-house established,
      HKCI-1, 2, 3 and 4, C1 and C2). The karyotypic abnormalities were examined by
      spectral karyotyping (SKY) and the chromosome loci defined were investigated for
      underlying deregulated genes by positional expression profiling. Quantitative RT
      PCR was employed to verify the profiling findings, and also used to examine a
      number of drug resistance-related candidate genes (MDR1, MRP1, MGMT, PTEN, BCL2,
      BAX, TP53 and P21). Our results indicated that the cytotoxic effect of DX in cell
      lines exhibited IC50 values that ranged from sensitive to resistant (0.07 to 3.55
      microM). While the overall chromosome aneuploidy did not correlate with DX
      resistance, aberrations on chromosome 10 demonstrated significant correlation
      with increasing IC50 (p=0.007). Positional profiling further suggested the
      consistent down-regulation of CGI-18 and ECHS1 on chromosome 10q. The array
      findings were substantiated by quantitative RT-PCR, which further pointed to a
      repressed ECHS1 expression in correlation with DX resistance (p=0.021). Among the
      candidate genes studied, an inverse relationship of P21 (p=0.034) and BAX
      (p=0.002) expression with DX resistance was also indicated. Our present study
      highlights the usefulness of multimodality approaches in identifying genetic
      markers, and further describes the novel finding of ECHS1 down-regulation in the
      DX chemo-resistance of HCC.

PMID- 15492827
TI  - Model building and quantitative analysis of a tandem immuno-capturing assay as a
      screening tool for breast cancer.
AB  - The onset of breast cancer appears to occur, on average, a decade earlier in
      Mexican women in comparison to American or European women. Early detection and
      prevention of breast cancer are of crucial importance to increase survival and
      improve quality of life. Based on the molecular elucidation of critical events
      leading to breast carcinogenesis, a tandem immuno-capturing blood test was
      developed as a quantitative population screening assay in view of providing a
      cost-effective and non-invasive alternative to population screening. Clinical
      analysis of 63 Mexican women within an age group of 35-70, revealed that
      Interstron activity increases from 800+/-65 IUJPA (Interstron Units) in the
      asymptomatic normal women to 994+/-100 IUJPA in the symptomatic/benign group,
      reaching 1289+/-81 IUJPA in the cancerous group. Accordingly, activity thresholds
      were established at 800 and 1200 IUJPA respectively, encompassing three risk
      groups: (i) Healthy Otherwise Normal (<800 IUJPA); (ii) Grey Risk Area (>800 and
      <1200 IUJPA), and (iii) At Risk group (>1200 IUJPA). Taking into account both
      baseline and clinical case reports, the Healthy Otherwise Normal group and the At
      Risk group were mostly homogeneous in nature, comprising a population of normal
      and cancer patients respectively. The Grey Risk group is heterogeneous, likely
      reflecting a transitional nature towards a potential early stage of breast
      disease development. Based on these results, a screening algorithm was developed
      as the underlining principle for population surveillance encompassing over 30,000
      Mexican women. The current screening results have enabled us to objectively
      prioritize medical attention to approximately 1 in 8 women out of the general
      population mapped within the At Risk group. Overall, our findings suggest that
      monitoring Interstron activity units provides a valuable quantitative screening
      analysis as to selectively streamline the population of women in need of early
      medical counseling and/or mammography, thereby enhancing both the quality and
      cost-effectiveness of preventative population surveillance programs targeting
      breast cancer.

PMID- 15492828
TI  - TGF-beta-induced upregulation of MMP-2 and MMP-9 depends on p38 MAPK, but not ERK
      signaling in MCF10A human breast epithelial cells.
AB  - Transforming growth factor (TGF)-beta has been reported to exert growth
      inhibitory activity in normal epithelial cells whereas it induces cell
      proliferation and invasive phenotypes in advanced carcinomas. Our previous study
      showed that MCF10A, a spontaneously immortalized "normal" breast epithelial cell
      line, is resistant to TGF-beta-induced growth inhibition, suggesting that
      conversion of TGF-beta growth inhibitory signaling into an oncogenic pathway may
      occur at the early stage of tumor development/progression. To address this issue,
      we investigated the TGF-beta signaling pathway and its role in phenotypic
      transformation of MCF10A cells. TGF-beta treatment induced changes in the MCF10A
      cell morphology from cuboidal to an elongated spindle-like shape, accompanied
      with down-regulation of epithelial cell marker E-cadherin. TGF-beta treatment was
      sufficient to induce migrative and invasive phenotypes in these cells, an
      important phenotypic conversion during tumor progression. We also showed that TGF
      beta treatment rapidly activated ERK-1/2 and p38 MAPK leading to upregulation of
      matrix metalloproteinase (MMP)-2 and MMP-9. Using chemical inhibitors and
      dominant negative mutants of MAPKs, we provide evidence that while both p38 MAPK
      and ERKs are required for TGF-beta-induced MCF10A cell migration and invasion,
      TGF-beta-induced MMP-2 and MMP-9 expression depends on p38 MAPK signaling, but is
      independent of ERK activity. This study demonstrates the roles of TGF-beta
      signaling pathways for induction of oncogenic signaling in preneoplastic human
      breast epithelial cells and will deepen our understanding of TGF-beta signaling
      in the progress of breast cancer.

PMID- 15492829
TI  - Analysis of isoform specific function of PP1 catalytic subunits in mammalian
      cells using siRNA.
AB  - Protein phosphatase type 1 (PP1) is involved in the regulation of numerous cell
      functions in mammalian cells. The major isoforms of PP1 catalytic subunit
      (PP1C)alpha, gamma1 and delta have nearly identical catalytic domain, but they
      vary in sequences at the amino and carboxyl termini. We previously showed that
      PP1Calpha is highly expressed in rat hepatoma cells. To examine isoform specific
      function of PP1C, each isoform was depleted from HeLa cells by RNA interference.
      The PP1Calpha-depleted cells rounded up and showed increased cell death,
      indicating that PP1Calpha is essential in cell proliferation. PP1Cgamma1-depleted
      cells slightly rounded up and have decreased G1 phase population and increased S
      phase population. The PP1Cdelta-depleted cells were enlarged, and appeared flat
      and rich in lamellipodia. These data suggested that each PP1C isoform has non
      redundant function in vivo.

PMID- 15492830
TI  - Soy isoflavones suppress invasiveness of breast cancer cells by the inhibition of
      NF-kappaB/AP-1-dependent and -independent pathways.
AB  - High consumption of soy products in some Asian countries has been linked to the
      low incidence of breast cancer in women. The chemopreventive effect of the soy
      isoflavone, genistein, has been observed through the suppression of cell
      proliferation, inhibition of angiogenesis and stimulation of apoptosis in breast
      carcinoma cells. Cancer metastasis consists of interdependent processes,
      including cell adhesion, migration and invasion. In the present study, we compare
      the effect of soy isoflavones in the form of aglycones (genistein, daidzein and
      glycitein) and glucosides (genistin, daidzin and glycitin) on the behavior of
      highly invasive breast cancer cells. Here we demonstrate that genistein
      suppresses cell adhesion and migration by inhibiting the constitutively active
      transcription factors NF-kappaB and AP-1, resulting in the suppression of
      secretion of urokinase-type plasminogen activator (uPA) in breast cancer cells
      MDA-MB-231. In addition, we show that all tested soy isoflavone aglycones
      (genistein, daidzein, glycitein) and glucosides (genistin, daidzin, glycitin)
      markedly reduced motility of MDA-MB-231 cells. However, only genistein and
      daidzein inhibited constitutively active NF-kappaB and AP-1 and suppressed
      secretion of uPA from breast cancer cells. Taken together, our results suggest
      that dietary soy isoflavones inhibit adhesion and motility of highly invasive
      breast cancer cells by distinct signaling pathways.

PMID- 15492831
TI  - Identification, validation, and clinical implementation of tumor-associated
      biomarkers to improve therapy concepts, survival, and quality of life of cancer
      patients: tasks of the Receptor and Biomarker Group of the European Organization
      for Research and Treatment of Cancer.
AB  - Guiding principles are provided and discussed on how to inform the physician
      scientist and cancer researcher about quality control systems to enable a
      consistent assessment of the clinical value of tumor-associated biomarkers. Next
      to cancer research itself, the Receptor and Biomarker Group of the European
      Organization for Research and Treatment of Cancer (RBG-EORTC) advises on
      methodologies, test kits and test reagents utilized for tumor biomarker
      determination. Tumor-associated biomarkers are important and clinically useful
      tools which can aid the early diagnosis of cancer, determine prognosis, predict
      therapy response, and monitor disease. With regard to clinical use of tumor
      associated bio-markers, quality assessment and quality assurance programs of the
      RBG-EORTC are crucially important issues. Test reagents, assays, and procedures
      for tumor sample collection and handling should be standardized. Furthermore,
      standard operating procedures (SOPs) should be developed for each type of tumor
      specimen. Assay formats and the quality of the tumor biomarker assay results have
      to be monitored by continuous within- and inter-laboratory proficiency testing.
      With this approach, a major step forward in the knowledge and understanding of
      the biological role and the clinical utility of tumor-associated biomarkers would
      be anticipated.

PMID- 15492832
TI  - Inhibition of matrix metalloproteinase-9 reduces in vitro invasion and
      angiogenesis in human microvascular endothelial cells.
AB  - The expression of matrix metalloproteinases (MMPs), particularly MMP-9, is
      significantly increased during tumor progression and is thought to play a major
      role in mediating angiogenic process. Since microvasculature plays an important
      role in controlling tumor growth, we investigated the effects of MMP-9 inhibition
      on endothelial cell migration and tube formation, two determinants of
      angiogenesis. Adenoviral-mediated MMP-9 downregulation inhibited endothelial cell
      migration in cell wounding and spheroid migration assays. To determine the
      effects of MMP-9 reduction in glioblastoma/endothelial co-cultures, we used a
      three-dimensional co-culture assay of glioblastoma spheroids and endothelial
      spheroids. Untreated controls showed invasion of both cell populations into each
      other whereas treatment of the co-cultures with adenoviral antisense MMP-9
      particles resulted in reduced invasion. Next, inhibition of MMP-9 by adenoviral
      vectors in endothelial cells was assessed for in vitro capillary-like structure
      formation either by co-culture with glioblastoma cells or exposure to
      glioblastoma-conditioned medium. Addition of conditioned medium from human
      glioblastoma cells to endothelial cells treated with antisense MMP-9 adenoviral
      vectors or co-cultures of glioblastoma cell lines with MMP-9-reduced endothelial
      cells resulted in reduced capillary-like tube formation demonstrating the key
      role of MMP-9 in endothelial cell network organization. Examination of in vitro
      capillary-like tube structure formation using Matrigel showed a significant
      decrease in MMP-9 downregulated endothelial cells as compared to controls. In
      conclusion, the inhibition of MMP-9 is required for inhibition of endothelial
      cell migration and tube formation and is likely to be of importance in cerebral
      angiogenesis for therapeutic targets.

PMID- 15492833
TI  - Epigenetic silencing of E- and P-cadherin gene expression in human melanoma cell
      lines.
AB  - The degree of E- and P-cadherin expressions inversely correlate with the
      progression stage of human melanoma. In the present study, we analyzed mechanisms
      of down-regulation of E- and P-cadherin gene expressions in 8 human melanoma cell
      lines. In 5 of the 8 melanoma cell lines, E-cadherin expression was lost or
      markedly decreased compared to that in normal melanocytes, and 4 of the 5
      melanoma cell lines lost P-cadherin expression. All of the melanoma cell lines
      expressed snail, which is known to encode a transcription repressor for E
      cadherin, at a higher level than melanocytes whereas expression levels of the
      snail varied among cell lines. Transduction of snail gene into MMAc cells which
      expressed a high level of E-cadherin and an extremely low level of snail
      decreased expression of E-cadherin but not P-cadherin. In contrast, transduction
      of antisense-snail gene into A375M cells which expressed no E-cadherin and a high
      level of snail restored expression of E-cadherin but not P-cadherin. Methylation
      specific PCR analysis revealed CpG methylation in the promoter region of E
      cadherin of MeWo and AKI cells. Further, the treatment with a demethylating
      agent, 5-azacytidine led AKI and A375M cells to re-express both E- and P
      cadherin. The results show E-cadherin gene is silenced by at least two distinct
      mechanisms (methylation and transrepression by Snail) in human melanoma cell
      lines whereas P-cadherin gene seems to be silenced by methylation but not by
      snail.

PMID- 15492834
TI  - Differentially expressed protein markers in human submandibular and sublingual
      secretions.
AB  - Proteome analysis of secretions from individual salivary glands is important for
      understanding the health of the oral cavity and pathogenesis of certain diseases.
      However, cross-contamination of submandibular (SM) and sublingual (SL) glandular
      secretions can occur. The close anatomic relationship of the SM and SL ductal
      orifices can lead to such contamination. Additionally, these glands may share
      common ducts. To insure the purity of SM/SL secretions for proteomic analysis, it
      is important to develop unique biomarkers which could be used to verify the
      integrity of the individual glandular saliva. In this study, a proteomics
      approach based on mass spectrometry and gel electrophoresis techniques was
      utilized to identify and verify a set of proteins (cystatin C, calgranulin B and
      MUC5B mucin), which are differentially expressed in SM/SL secretions. SM/SL
      fluids were obtained from nine healthy subjects. Cystatin C was found to be an SM
      selective protein as it was found in all SM fluids but not detected in two SL
      fluids. MUC5B mucin and calgranulin B, on the other hand, were found to be SL
      selective proteins. All SL samples contained MUC5B mucin, whereas MUC5B mucin was
      not detected in four SM samples. Eight of the SL samples contained calgranulin B;
      however, calgranulin B was absent in eight SM samples. This set of protein
      markers, especially calgranulin B, can be used to determine the purity of SM/SL
      samples, and therefore identify potential individuals who do not exhibit cross
      contaminated SM/SL secretions, an important requirement for subsequent proteome
      analysis of pure SM and SL secretions.

PMID- 15492835
TI  - Trichostatin A induces apoptosis of p815 mastocytoma cells in histone acetylation
      and mitochondria-dependent fashion.
AB  - Although inhibition of histone deacetylase has been demonstrated to induce
      apoptosis of various cancer cells, there is no report on its effect on mast cell
      demise to date. Here we studied whether a histone deacetylase inhibitor
      Trichostatin A (TSA) produces apoptosis in p815 mastocytoma cells. TSA
      prominently increased the amount of acetylated histones, H3, H4, H2A and H2B, in
      p815 mastocytoma cells. TSA reduced the viability of p815 mastocytoma cells, and
      many apoptotic manifestations such as generation of DNA fragmentation, activation
      of caspase-3, cleavage of poly (ADP-ribose) polymerase (PARP), and increase of
      DNA hypoploidy proved that the reduction of viability resulted from apoptosis.
      Whereas TSA treatment increased the expression level of Bad, it decreased the
      level of Bcl-2, Bcl-xL, and X-linked inhibitor of apoptosis protein. The
      reduction of mitochondrial membrane potential, the release of cytochrome c and
      Smac/DIABLO to cytosol, and mitochondrial localization of Bad were also shown.
      Taken together, TSA induces apoptosis on p815 mastocytoma cells in histone
      acetylation- and mitochondria-dependent fashion. Our data therefore provide the
      possibility that TSA could be considered as a novel therapeutic strategy for
      mastocytoma from its apoptosis-inducing activity.

PMID- 15492836
TI  - Proteasomes act in the pre-mitochondrial signal transduction route towards
      roscovitine-induced apoptosis.
AB  - The role of the ubiquitin-proteasome pathway during roscovitine induced apoptosis
      was evaluated in the non-small cell lung carcinoma cell line MR65. To this end
      specific inhibitors of proteasome activity, MG132 and lactacystin were used.
      Addition of MG132 or lactacystin, 1 h prior to the addition of the CDK-inhibitor
      roscovitine to the cell cultures inhibited apoptosis significantly, as measured
      by PS exposure, cytokeratin 18 cleavage and caspase-3 activation. Furthermore, we
      show that inhibition of proteasome activation prior to induction of apoptosis by
      roscovitine prevents loss of mitochondrial inner transmembrane potential
      (DeltaPsim). In addition we found that MG132 and lactacystin prevent release of
      cytochrome c from the mitochondrion. In contrast to the above findings we see no
      effect of proteasome inhibition in Fas-mediated apoptosis. Taken together our
      data suggest a specific role for proteasomes very early in roscovitine-induced
      apoptosis, upstream from the caspase cascade and mitochondrion.

PMID- 15492837
TI  - p16INK4a polymorphism: associations with tumour progression in patients with
      sporadic colorectal cancer.
AB  - Deregulated tumour expression of p16INK4a has previously been described in
      association with clinical progression in sporadic colorectal cancer patients
      (CRC). Furthermore, p16INK4a promoter hypermethylation leading to gene silencing
      has been shown to occur in advanced colorectal tumours and has been associated
      with patient survival. p16INK4a is polymorphic, with variant alleles being
      associated with tumour progression in melanoma. In this study we have examined
      p16INK4a polymorphism as a marker of tumour progression in sporadic CRC.
      Polymorphic sites G/A(442), C/G(500), and C/T(540), were studied, these alleles
      obeyed Hardy Weinberg equilibrium in a control group, but not in the CRC cases.
      G/A(442) and CG(500) alleles were in linkage disequilibrium in both cases and
      controls. In controls the C/T(540) alleles demonstrated no linkage with either
      other site, whilst an association was demonstrated between C/G(500) and C/T(540)
      alleles in the cases (p=0.011). Furthermore, the distribution of C/T(540)
      genotypes was different between the groups (p=0.002). Within the CRC cases,
      patients with the GG(442) genotype were more commonly associated with decreased
      tumour differentiation (p=0.018), advancing Dukes' stage (p=0.006) and T-stage
      (p=0.007) than patients with the GA(442) and AA(442) genotypes. Patients with the
      CC(500) genotype were more commonly associated with decreased tumour
      differentiation (p=0.012), advancing Dukes' stage (p=0.015), and N-stage
      (p=0.031). No associations between patient C/T(540) genotype and clinical
      prognostic parameters were found. An analysis of patient tumour expression with
      p16INK4a genotype revealed patients with the CC(500) genotype were more commonly
      associated with reduced tumour p16 expression (p=0.046). In summary our data
      indicate that p16INK4a polymorphism is associated with tumour progression in
      patients with sporadic CRC.

PMID- 15492838
TI  - Primary B-cell lymphoma of the skin: the Sheffield Lymphoma Group Experience
      (1984-2003).
AB  - The clinical presentation, treatment and outcome were retrospectively evaluated
      in a series of 66 patients with primary B-cell lymphoma of the skin, referred to
      the Sheffield lymphoma group (SLG) between 1984 and 2003. This is the largest
      series reported from the UK. The lymphoma database was searched and clinical
      records were reviewed. Absence of any detectable extracutaneous lesion and the
      expression of B-cell restricted antigens by neoplastic cells were the essential
      criteria for selection of cases. The cohort included 37 (56%) males and 29 (44%)
      females with a mean age of 59 years. The most commonly involved site was the
      trunk and the disorder typically showed non-aggressive clinical behaviour; the
      majority of the patients presented with stage I (82%) disease with a tendency to
      remain localised to a limited area of the skin. Follicular lymphoma was the most
      common histologic subtype (35%), the next most frequent was the diffuse large
      cell lymphoma (32%) whereas marginal zone lymphoma constituted 15%. The majority
      (47%) of patients were treated with radiotherapy for localised disease whereas
      chemotherapy was given in 20% of patients, with single agent chlorambucil being
      most frequently used. Surgical excision as the sole modality of treatment was
      adequate in 33%. Disease-free survival (DFS) was 91% at 1 year, 82% at 2 years
      and 60% at 5 years. DFS was significantly lower with older age (>45 years), leg
      lesions, generalised and multiple lesions, and for those treated with
      chemotherapy. The survival at 5 and 10 years was 80%. The histologic grade, leg
      involvement and the number of lesions were the most significant variables
      affecting overall survival. Only 7 patients died of lymphoma. In conclusion,
      primary cutaneous B-cell lymphoma represents a specific entity concerning
      clinical behaviour, response to treatment, and overall prognosis.

PMID- 15492839
TI  - Transactivation of E-cadherin is not involved in the activity of EGF receptor in
      colorectal carcinoma cells.
AB  - In epithelial cells, the cell surface glycoprotein E-cadherin is a key molecule
      in the establishment of cell-cell adhesion. In addition to its contribution to
      cell adhesion, E-cadherin was found to induce ligand-independent activation of
      the EGF receptor (EGFR), likely as a result of their co-clustering. As it has
      also been reported that ligand activation of the overexpressed EGFRs disturb E
      cadherin-mediated cell-cell adhesion, we analyzed E-cadherin-EGFR interactions
      and their consequences in A431 cells and in two colorectal cancer cell lines
      using immunoblotting and analyzes of several protein kinase activities.
      Activation of the PI3-K/Akt/GSK-3 signaling pathway upon EGF treatment that we
      observed in the analyzed cells indicates that EGFRs are functional even in the
      colorectal cancer cells containing a low density of EGFRs. The transactivation of
      EGFR by E-cadherin did not occur either in the colorectal cancer cells tested or
      in A431 cells containing a high density of both EGFRs and E-cadherin on their
      surface. This observation suggests that high amounts of both molecules on the
      surface of tumour cells did not predetermine ligand-independent activation of
      EGFRs.

PMID- 15492840
TI  - Polymorphisms in the methylenetetrahydrofolate reductase gene and prostate cancer
      risk.
AB  - Methylenetetrahydrofolate reductase (MTHFR) catalyzes the synthesis of 5
      methyltetrahydrofolate, which is involved in the methylation of homocysteine to
      methionine. Genetic polymorphisms that decrease MTHFR activity result in an
      altered cancer risk depending on folic acid intake. In this study we examined the
      C677T and A1298C polymorphisms of the MTHFR gene in specimens from 81 patients
      with prostate cancer and 42 controls selected from patients with benign prostatic
      hypertrophy (BPH). Genomic DNA was isolated from archived formaldehyde-fixed and
      paraffin-embedded tissue blocks. MTHFR genotypes were determined by restriction
      fragment-length-polymorphism polymerase chain reaction. The MTHFR polymorphism
      frequencies in the prostate-cancer and BPH specimens were, respectively, 60% and
      48% for 677CC, 31% and 48% for 677CT, 9% and 5% for 677TT, 36% and 43% for
      1298AA, 53% and 40% for 1298AC, and 11% and 17% for 1298CC. Although such
      differences fall within the realm of chance variation (P>0.05), the data suggest
      that the 677CT genotype may be associated with a reduced risk of prostate cancer:
      the age-adjusted odds ratio (aOR) was 0.6 [95% confidence interval (CI): 0.3
      1.4]; the odds-ratio reduction was similar in both blacks and whites (aOR=0.4 in
      blacks, and 0.6 in whites); and when polymorphisms at the 677 and 1298 loci were
      analyzed in conjunction, a lower frequency of the 677CT-1298AA genotype was
      observed in the patients with prostate cancer (aOR=0.3, 95% CI: 0.1-1.1). This
      particular genotype, moreover, was associated with lower Gleason score tumors
      (aOR=0.1 for Gleason-score 7 versus 6 tumors, 95% CI: 0.0-0.7) and earlier stage
      disease (aOR=0.3 for stage III versus II, 95% CI: 0.3-2.6). These findings
      suggest that polymorphisms of the MTHFR gene may alter the risk of developing
      prostate cancer.

PMID- 15492841
TI  - Correlation between topoisomerase-IIalpha gene amplification and protein
      expression in HER-2 amplified breast cancer.
AB  - Topoisomerase-IIalpha (topo-II) is a molecular target for topo-II inhibitors,
      which makes it a potential predictive marker of responsiveness to these agents.
      We aim to correlate topo-II gene and protein status on 103 HER-2 amplified breast
      cancer samples. Paraffin-embedded blocks were screened by FISH for topo-II gene
      amplification (topo-II: CEP17 ratio >/=1.5; triple probe by Vysis inc.) and
      analyzed by IHC for topo-II protein expression (continuous variable; clone KiS1)
      and Ki-67 (positive if >25% of stained cells; clone MIB-1). Topo-II gene
      amplification was observed in 36.9% (38/103) of the HER-2 amplified study
      population. HER-2 amplification level (e.g. copy number) was not shown to be
      predictive for topo-II amplification. The median percentage of topo-II positively
      stained cells by IHC for topo-II non-amplified and amplified cases were 5% and
      10%, respectively. A weak but significant correlation was observed between topo
      II gene amplification level and percentage of positively stained cells
      (Spearman's ranks correlation coefficient of 0.23, p=0.02), the observed
      correlation being higher in patients with positive staining for Ki-67. Contrary
      to HER-2, where gene amplification is almost always correlated with protein
      overexpression in breast cancer, topo-II gene amplification apparently does not
      always lead to protein overexpression, at least when the latter is evaluated by
      IHC. Other factors, specifically the tumor proliferation status, may interfere
      with the topo-II protein status. Although the great majority of topo-II gene
      aberrations occur in HER-2 positive tumors, the level of HER-2 amplification does
      not predict for topo-II amplification.

PMID- 15492842
TI  - Candidate genes upregulated in density dependent growth inhibition of lung cancer
      cells.
AB  - Prognosis of lung cancer remains poor despite the recent development of new
      chemotherapeutic agents. Novel therapeutic strategies therefore need to be
      developed. The search for factors inhibiting tumor growth in a
      paracrine/autocrine fashion might result in a well-tolerated adjuvant tumor
      therapy. In this study we aimed to identify candidate genes for such inhibitors
      of tumor cell growth. Native and heat-inactivated supernatants of confluent, slow
      growing H460 tumor cell cultures and of sparse (non-confluent), fast growing H460
      tumor cell cultures were tested in proliferation assays. We observed that native
      supernatant of confluent H460 and A549 cells contain proteins inhibiting tumor
      cell growth of NSCLC cell lines. Microarray gene expression analysis of sparse
      and confluent H460 cells exhibited overexpression of 7 candidate genes in
      confluent, slow growing cells. The products of these genes possess cell growth
      inhibitory function and also exist in the extracellular compartment. The
      increased expression level of these genes was verified using real-time RT-PCR
      analysis. Our results show that especially components of IGF pathway appear to be
      involved in exogenous growth inhibition of confluent cells. Further
      investigations of these factors may result in the identification of
      autocrine/paracrine tumor cell growth inhibitory proteins for future use in
      clinical applications.

PMID- 15492843
TI  - Molecular analysis of the erbB gene family calmodulin-binding and calmodulin-like
      domains in astrocytic gliomas.
AB  - Primarily involved in cell proliferation and differentiation processes, the
      plasma membrane-bound ErbB tyrosine kinase receptor family is formed by four
      members: erbB1/EGFR, erbB2/HER2/Neu, erbB3/HER3 and erbB4/HER4. Calmodulin (CaM)
      is a Ca2+-binding protein involved in the regulation of multiple intracellular
      processes that binds directly to EGFR in the presence of Ca2+, inhibiting its
      tyrosine kinase activity. Two main regions in the receptor have been implicated
      in this relationship: the calmodulin-binding domain (CaM-BD) and the calmodulin
      like domain (CaM-LD); their sequences are highly conserved in other members of
      this family of receptors. The presence of mutations, amplification and/or
      overexpression and genomic rearrangement of these domains was investigated for
      all four erbB family genes in a series of 89 glial tumors, including 44 WHO grade
      IV glioblastomas, 21 WHO grade III anaplastic astrocytomas, and 24 WHO grade II
      astrocytomas. Gene alterations were only found in the regions of interest in
      EGFR. One glioblastoma showed an in frame tandem duplication of the intracellular
      region including CaM-LD (exons 18-25). CaM-BD gene overdose was evidenced in 18
      tumors that showed EGFR amplification in other domains. Over-expression of CaM-BD
      and CaM-LD was detected in 6 and 17 cases, respectively, of the 19 tumors in
      which this study was performed. The other three genes coding for the ErbB
      receptors did not present point mutations, or rearrangements, and only a very low
      amplification rate was found for erbB2 (1 case) and erbB3 (4 cases). No
      overexpression of erbB2, erbB3 or erbB4 was detected. These findings suggest that
      EGFR is the main erbB gene family member non-randomly involved in malignant
      glioma development, and that the two domains under study, due to their high
      conservation and wide separation in the EGFR sequence, are good marker regions
      for evaluating EGFR/erbB1 gene amplification, as well as for analysing the
      presence of transcripts corresponding to truncated cytosolic forms of the
      receptor in these tumors.

PMID- 15492844
TI  - Human FOX gene family (Review).
AB  - Human Forkhead-box (FOX) gene family consists of at least 43 members, including
      FOXA1, FOXA2, FOXA3, FOXB1, FOXC1, FOXC2, FOXD1, FOXD2, FOXD3, FOXD4, FOXD5
      (FOXD4L1), FOXD6 (FOXD4L3), FOXE1, FOXE2, FOXE3, FOXF1, FOXF2, FOXG1 (FOXG1B),
      FOXH1, FOXI1, FOXJ1, FOXJ2, FOXJ3, FOXK1, FOXK2, FOXL1, FOXL2, FOXM1, FOXN1,
      FOXN2 (HTLF), FOXN3 (CHES1), FOXN4, FOXN5 (FOXR1), FOXN6 (FOXR2), FOXO1 (FOXO1A),
      FOXO2 (FOXO6), FOXO3 (FOXO3A), FOXO4 (MLLT7), FOXP1, FOXP2, FOXP3, FOXP4, and
      FOXQ1. FOXE3-FOXD2 (1p33), FOXQ1-FOXF2-FOXC1 (6p25.3), and FOXF1-FOXC2-FOXL1
      (16q24.1) loci are FOX gene clusters within the human genome. Members of FOX
      subfamilies A-G, I-L and Q were grouped into class 1 FOX proteins, while members
      of FOX subfamilies H and M-P were grouped into class 2 FOX proteins. C-terminal
      basic region within the FOX domain was the common feature of class 1 FOX
      proteins. FOXH1 and FOXO1 mRNAs are expressed in human embryonic stem (ES) cells.
      FOXC1, FOXC2, FOXE1, FOXE3, FOXL2, FOXN1, FOXP2 and FOXP3 genes are mutated in
      human congenital disorders. FOXA1 gene is amplified and over-expressed in
      esophageal and lung cancer. FOXM1 gene is up-regulated in pancreatic cancer and
      basal cell carcinoma due to the transcriptional regulation by Sonic Hedgehog
      (SHH) pathway. FOXO1 gene is fused to PAX3 or PAX7 genes in rhabdomyosarcoma.
      FOXO3 and FOXO4 genes are fused to MLL gene in hematological malignancies.
      Deregulation of FOX family genes leads to congenital disorders, diabetes
      mellitus, or carcinogenesis. Expression profiles, genetic alterations and
      epigenetic changes of FOX family genes as well as binding proteins and target
      genes of FOX family transcription factors should be comprehensively investigated
      to develop novel therapeutics and preventives for human diseases.

PMID- 15492845
TI  - The possible correlation of Notch-1 and Notch-2 with clinical outcome and tumour
      clinicopathological parameters in human breast cancer.
AB  - The Notch-1 and Notch-2 receptors play crucial roles in cell fate determination
      through interaction with the Delta/Serrate/Lag-2 family of ligands. The function
      of Notch signalling in tumourigenesis is still unclear, however, reports have
      demonstrated unregulated Notch activity in a variety of human cancers. We
      quantified Notch-1 and Notch-2 expression, in association with clinical outcome,
      in tissue samples from breast cancer patients (normal specimens n=24, breast
      cancer specimens n=97). We used qualitative and quantitative RT-PCR analysis,
      along with immunohistochemical staining to examine Notch-1 and Notch-2 expression
      in association with the patients clinical parameters (median follow-up 72
      months). Our results show that there are aberrant levels of Notch-1 and Notch-2
      in breast cancer tissues compared with normal breast tissue. Examination of the
      breast cancer patients' clinicopathological parameters reported that a high level
      of Notch-1 may be associated with a poorer outlook for the breast cancer patient,
      while a high level of Notch-2 correlated to a higher chance of survival. Notch-1
      and Notch-2 also appear to play crucial and contrasting roles in breast tumour
      differentiation. Notch-1 expression was low in grade 1 tumours and increased in
      poorly-differentiated tumours, whereas, Notch-2 expression was high in well
      differentiated tumours and reduced in breast tumours with poor differentiation.
      Therefore, Notch-1 may possess tumour-promoting functions, while Notch-2 could
      play a tumour-suppressive role in human breast cancer. These results support the
      notion that suppression of Notch-1 activity may represent a novel therapeutic
      strategy.

PMID- 15492846
TI  - Co-expression of VEGF, c-Met and HGF/SF in secondary pleural tumors.
AB  - Tumor angiogenesis is influenced by a large number of angiogenic factors among
      which vascular endothelial growth factor (VEGF) is one of the most important
      cytokines. Together with hepatocyte growth factor/scatter factor (HGF/SF), c-Met
      receptor forms a paracrine signaling system. The aim was to study the
      characterization of the proteins, VEGF, c-Met and HGF/SF with expression pattern
      and possible co-expression in secondary pleural tumors. Biopsy specimens of the
      pleural region from 70 patients were chosen and analyzed using
      immunohistochemistry and in situ hybridization. In the investigated tumors, a
      marked intracytoplasmic expression, sometimes over-expression of VEGF, c-Met and
      HGF/SF was detected. This expression was not connected to certain tumor types or
      a certain histogenetic origin of the tumor. These results indicate a role of
      these factors in angiogenesis. The synthesis of VEGF and c-Met within the tumor
      cells was established by in situ hybridization. There was a significant co
      expression of VEGF and c-Met/HGF. Thus, autocrine stimulation of these angio
      genetically effective systems may be present here. Importantly, the autocrine
      mechanism between over-expressed c-Met and HGF/SF in malignant tumors, already
      preferred by other authors, with demonstration of the proteins in the same tumor
      cells, has to be assumed in the process of pleural metastatic spread.
      Simultaneous synthesis of these three different proteins is also possible via the
      plasminogen-urokinase system. VEGF is reported to increase vascular permeability,
      which in turn causes pleural effusions. The results presented here may be the
      basis for possible future palliative therapeutical strategies in malignant
      pleural effusions.

PMID- 15492847
TI  - Analysis of the PTCH1 signaling pathway in ovarian dermoids.
AB  - Dermoids belong to the group of developmental cysts and arise from germ cells.
      Studies on these tumors may therefore increase our understanding of normal germ
      cell development within different environments and cell lines derived from these
      lesions may also constitute an important vehicle for studying neoplasia and
      differentiation. Recently, we investigated the status of the PTCH1 locus in a
      large set of sporadic non-inflammatory, developmental cystic lesions. Our data
      showed allelic loss of microsatellite markers in close vicinity to the PTCH1
      locus in both odontogenic keratocysts and dentigerous cysts as well as in ovarian
      dermoid cysts (ODC). In this study, we closely examined the status of the PTCH1
      gene in ODCs. Although about 25% of cysts demonstrated LOH at the PTCH1 locus, no
      nonsense or missense mutations in the coding region of PTCH1 were detected in
      genomic DNA isolated from any of the ODCs examined by direct sequencing. Staining
      with PTCH1 and GLI1 antibodies showed that proteins were present in virtually all
      epithelial linings, with variable staining intensity not correlated with LOH and
      generally weaker for GLI1. However, cDNA microarray analysis performed on cell
      lines derived from ODCs did not show any significant alteration in the expression
      of the analyzed target genes of PTCH1 signaling in any of the cell lines
      examined, except for CyclinD1 (and several other genes generally not associated
      with PTCH1 signaling).

PMID- 15492848
TI  - Stable long-term induction of perforin-positive CD8+ T cells in gut by oral
      administration of streptococcal preparation OK-432.
AB  - Perforin is known as a pore-forming cytotoxic granule released from cytotoxic T
      cells. Previous experiments in vitro revealed the presence of precursor cells
      that are capable of producing perforin in the immune system cells. The present
      study was undertaken to examine whether perforin-positive cells could be induced
      in the digestive tract and to characterize their precursor cells. Expression of
      perforin-positive cells in the intestine of Balb/c mice induced by OK-432 was
      analyzed by immunohistochemical staining and RT-PCR. Oral treatment of Balb/c
      mice with OK-432 resulted in the occurrence of perforin-positive cells in the
      inferior segment of small intestine, the superior segment of large intestine,
      mesenteric lymph nodes and spleen. In the small intestine, perforin-positive
      cells were found in the lamina propria mucosa. The presence of perforin-positive
      cells was also noted following long-term OK-432 treatment. Similar results were
      obtained following treatment with biological response modifiers such as
      lipopolysaccharide. In mice with GVHD (graft-versus-host disease), the presence
      of perforin-positive cells was noted in the small intestine and spleen. When the
      serial sections of the small intestinal mucosa from OK-432-treated mice were
      immunostained with anti-perforin, anti-CD8 and anti-asialo-GM1 antibodies, the
      perforin-positive cells were found to be CD8-positive. The results suggest that
      CD8(+) cells in lamina propria mucosa play a significant role as effectors in the
      mucosal immune system which is activated by various stimuli.

PMID- 15492849
TI  - Hypermethylation of the p16 gene in normal oral mucosa of smokers.
AB  - The oral cavity is the sixth most common anatomical localization of head and neck
      carcinoma in men. Detection of oral carcinomas in the early asymptomatic stages
      improves cure rates and the quality of life. Tobacco smoking and alcohol drinking
      are the most important known risk factors for the development of head and neck
      tumors, suggesting that the exposure to these risk factors may increase the
      predisposition for genetic and epigenetic alterations, such as DNA methylation.
      The presence of methylated CpG islands in the promoter region of human genes can
      suppress their expression due to the presence of 5-methylcytosine that interferes
      with the binding of transcription factors or other DNA-binding proteins
      repressing transcription activity. Hypermethylation leading to the inactivation
      of some tumor suppressor genes, such as p16, has been pointed out as an initial
      event in head and neck cancer. Our aim was to evaluate an early diagnostic method
      of oral pre-cancerous lesions through the analysis of methylation of the p16
      gene. DNA samples from normal oral mucosa and posterior tongue border from 258
      smokers, without oral cancer, were investigated for the occurrence of p16
      promoter hypermethylation. The methylation status of the p16 gene was analyzed
      using MS-PCR (methylation-sensitive restriction enzymes and PCR amplification),
      MSP (Methylation-specific PCR) or direct DNA sequence of bisulfite modified DNA.
      Hyper-methylation was detected in 9.7% (25/258) of the cases analyzed. These
      findings provide further evidence that epigenetic alteration, leading to the
      inactivation of the p16 tumor suppressor gene is an early event that might confer
      cell growth advantages contributing to the tumorigenic process. Thus, the
      detection of abnormal p16 methylation pattern may be a valuable tool for early
      oral cancer detection.

PMID- 15492850
TI  - Novel mutations in TNFRSF1A in patients with typical tumor necrosis factor
      receptor-associated periodic syndrome and with systemic lupus erythematosus in
      Japanese.
AB  - Molecular defects of TNFRSF1A was investigated in members of a family presenting
      with typical phenotypes of tumor necrosis factor receptor-associated periodic
      syndrome (TRAPS) and in patients with the autoimmune disorders, systemic lupus
      erythematosus (SLE) and rheumatoid arthritis (RA). Genomic DNA from the members
      of a family with typical TRAPS, as well as from 100 patients with SLE, 100
      patients with RA and 100 healthy individuals, was studied for mutations in exons
      2, 3 and 4 of the TNFRSF1A gene. All individuals were Japanese. Three novel
      missense mutations were identified in the TNFRSF1A. The C70G mutation was
      identified in family members with typical TRAPS, which was the second case in
      eastern Asian population. In addition, the T61I and R104Q mutations were each
      identified in 2 of the 100 SLE patients. The T61I mutation was identified in one
      of the 100 healthy individuals. No mutations were identified in the 100 RA
      patients. Functional analysis revealed that PMA-induced shedding of TNFRSF1A from
      PBMCs was impaired in a patient carrying T61I. A larger scale of study will
      clarify whether these two mutations, T61I and R104Q, are associated with chronic
      inflammatory disorders, such as SLE, or not.

PMID- 15492851
TI  - Anti-angiogenic effect of pyridoxal 5'-phosphate, pyridoxal and pyridoxamine on
      embryoid bodies derived from mouse embryonic stem cells.
AB  - We previously demonstrated anti-angiogenic activity of pyridoxal 5'-phosphate
      (PLP) and pyridoxal (PL) using in vitro and ex vivo angiogenesis models and anti
      colon tumor effect of vitamin B(6) in mice. There is growing evidence that
      endothelial progenitor cells (EPCs) in circulation contribute to tumor-induced
      angiogenesis. It is of importance to clarify whether EPC differentiation is
      involved in the mechanism of anti-angiogenic effect of vitamin B(6). In this
      study, we investigated the effect of vitamin B(6) on angiogenesis in embryonic
      stem cell-derived embryoid bodies (EBs). PLP suppressed angiogenesis in EBs at
      >or=100 microM. Among the vitamin B(6) compounds at the concentration of 200
      microM, PL, as well as PLP, was the most effective suppressor of vasculogenesis,
      while pyridoxine was inactive. These results were consistent with their effects
      in rat aorta and endothelial cell assays. Interestingly, pyridoxamine (PM), which
      had no effect in rat aorta and endothelial cell assays, also exerted a
      significant suppressive effect in this model. This study demonstrated an
      inhibitory effect of PM on vasculogenesis in this EB model as well as PLP and PL,
      and suggests that suppression of EPC differentiation is at least in part
      responsible for the mechanism of the anti-angiogenesis effect of vitamin B(6).

PMID- 15492852
TI  - Alteration of the MDM2-p73-P14ARF pathway related to tumour progression during
      urinary bladder carcinogenesis.
AB  - Transitional cell carcinomas (TCC) of the urinary bladder develop by a multistep
      process characterized by various stages of transformation differing in their
      grade of malignancy and biological behaviour. Since the prospective clinical
      outcome cannot be reliably predicted on histopathological grounds, we analysed
      the mRNA expression of the MDM2-p73-P14ARF tumour surveillance pathway in an
      attempt to detect alterations of gene activity, allowing a better understanding
      of the mechanisms responsible for conversion of low to high malignant TCC.
      Expression of the mRNA was determined in 71 TCC of various grades and stages
      using the real-time quantitative reverse transcription-polymerase chain reaction.
      The MDM2-p73-P14ARF pathway was dominated by the MDM2 gene, the mRNA expression
      of which proved to be significantly (5-fold) lower in advanced high-grade, high
      stage than in superficial low-grade, low-stage TCC. Conversely, the expression of
      p73 mRNA increased with increasing tumour grades and stages, while the activity
      of the P14ARF gene was not substantially altered during early and late phases of
      urothelial carcinogenesis. Analysing the expression of spliced variants of MDM2
      mRNA, we found a heterogeneous pattern including a novel splicing transcript
      coding for an abnormal protein. Promoter hypermethylation of P14ARF occurred in
      10% of the TCC with an under-expression of mRNA. An analysis of the effects of
      lifestyle and occupational bladder cancer risk factors revealed that TCC of
      smokers showed a 2-fold elevated expression of MDM2 mRNA and an approximately 2
      fold lower expression of P14ARF mRNA, whereas the activity of the p73 gene was
      unchanged. Heavy coffee consumption was associated with a 2-fold decreased
      expression level of P14ARF mRNA. Exposure to certain occupational hazards
      (plastic products, paints and lacquer, polycyclic hydrocarbons, chemical
      solvents) was observed to modulate the activity of the genes analysed. Our
      findings suggest that an alteration in the MDM2-p73-P14ARF pathway is involved in
      the progression of bladder cancer to a more malignant and aggressive form.

PMID- 15492853
TI  - Anti-monocyte chemoattractant protein-1 gene therapy prevents dimethylnitrosamine
      induced hepatic fibrosis in rats.
AB  - Monocyte chemoattractant protein-1 (MCP-1) has been implicated in the process of
      hepatic inflammation, recruiting monocytes and lymphocytes during liver injury.
      MCP-1 also activates directly hepatic stellate cells, which play a major role in
      hepatic fibrosis. However, it remains unclear whether blockage of MCP-1 signaling
      could prevent hepatic fibrosis in vivo. We evaluated a strategy for anti-MCP-1
      gene therapy against hepatic fibrosis by transfecting an amino-terminal deletion
      mutant, lacking the amino-terminal codons 2 to 8 of the human MCP-1 gene and
      designated 7ND, into skeletal muscle in a rat experimental model of
      dimethylnitrosamine (DMN)-induced fibrosis. Anti-MCP-1 gene therapy decreased
      significantly the occurrence of DMN-induced hepatic fibrosis, evaluated by
      computed image analysis and by measurement of hydroxyproline contents of the
      liver, accompanied by a reduction in the expressions of alpha-smooth muscle
      actin. This treatment also caused a significant decrease in hepatic tissue levels
      of interleukin (IL)-12 (Th1 cytokine) and an increase in those of IL-10 (Th2
      cytokine), indicating a change in the Th1/Th2 cytokine balance in the liver. In
      conclusion, blockade of MCP-1 after intramuscular transfer of the 7ND gene
      suppressed hepatic fibrosis, and this strategy may be a useful and feasible gene
      therapy against hepatic fibrosis.

PMID- 15492854
TI  - Effects of neuropeptides B and W on the secretion and growth of rat
      adrenocortical cells.
AB  - Neuropeptide-B (NPB) and neuropeptide-W (NPW) are recently discovered endogenous
      ligands of the GPR7- and GPR8-receptors (R), which in humans are expressed in the
      hypothalamus and probably involved in the regulation of energy homeostasis and
      neuroendocrine axes. GPR8-Rs are absent in rodents, where the GPR8-like-R has
      been described. Reverse transcription-polymerase chain reaction detected the
      expression of NPB, NPW, GPR7-R and GPR8-like-R mRNAs in rat adrenocortical cells
      (both freshly-dispersed and 4-day-cultured cells). NPB did not acutely (60-min
      exposure) alter basal aldosterone secretion from freshly dispersed zona
      glomerulosa cells, while NPW raised it. Both NPB and NPW enhanced ACTH-stimulated
      aldosterone secretion and did not affect either basal or ACTH-stimulated
      corticosterone production by dispersed zona fasciculata/reticularis (ZF/R) cells.
      The prolonged (4-day) exposure to NPW, but not NPB, raised corticosterone
      secretion from cultured ZF/R cells, and both neuropeptides increased the
      proliferation rate of cultured cells. Taken together, our findings indicate that
      NPB and NPW affect rat adrenocortical function, so they may be included in that
      large family of peptides involved in the autocrine-paracrine stimulation of
      secretion and growth of adrenal cortex.

PMID- 15492855
TI  - Ghrelin inhibits in vitro angiogenic activity of rat brain microvascular
      endothelial cells.
AB  - Ghrelin, a 28-amino acid peptide originally isolated from rat stomach, is an
      endogenous ligand of the growth hormone secretagogue receptor (GHS-R). Evidence
      has been provided that ghrelin and GHS-Rs are highly expressed in the
      cardiovascular system, including endothelial cells (ECs), of which they regulate
      the growth in vitro. It, therefore, seemed worthwhile to investigate the effect
      of ghrelin on in vitro angiogenesis, using cultures of rat ECs derived from brain
      microvessels (neuromicrovascular ECs, NECs). ECs, when cultured on a supportive
      matrix, form a network of tubule-like structures, and such process is enhanced by
      the classic angiogenic factors, including fibroblast growth factor-2 (FGF-2).
      After seeding on Matrigel-coated wells, NECs formed within 18 h a meshwork of
      capillary-like structures; vinblastine (2 x 10(-12) M) disrupted the meshwork,
      while FGF-2 (50 ng/ml) increased its density. Ghrelin (10(-8) M) exerted a
      vinblastine-like effect and counteracted the stimulatory action of FGF-2.
      Computerized image-analysis confirmed these observations. FGF-2 enhanced the
      proliferation rate and lowered the apoptotic rate of NECs cultured on plastic
      wells, and ghrelin exerted opposite effects and completely reversed the
      proliferogenic and antiapoptotic actions of FGF-2. In contrast to vinblastine,
      ghrelin did not increase lactate dehydrogenase release from cultured NECs,
      thereby ruling out the possibility that its effects may ensue from an aspecific
      cytotoxic action. FGF-2 enhanced tyrosine kinase (TK) and mitogen activated
      protein kinase (MAPK) p42/p44 activities of NECs. Ghrelin significantly decreased
      TK and MAPK p42/p44 activities and effectively counteracted the effect of FGF-2.
      Taken together, the present findings indicate that ghrelin exerts a marked in
      vitro antiangiogenic action, and that the mechanism underlying this effect
      involves the inhibition of TK/MAPK-dependent cascades.

PMID- 15492856
TI  - Glutathione S-transferase T1 deletion is a risk factor for developing end-stage
      renal disease in diabetic patients.
AB  - Reactive oxygen metabolites may contribute to the development of end-stage renal
      disease (ESRD) in diabetic and hypertensive patients. In this study, we used
      multiplex polymerase chain reaction (PCR) to analyze polymorphisms of two
      endogenous antioxidant genes, glutathione S-transferase M1 (GSTM1) and
      glutathione S-transferase T1 (GSTT1), and to determine their role in the
      development of ESRD in diabetic and hypertensive patients. Our results showed
      that homozygous deletion of the GSTT1 gene is a risk factor for developing ESRD
      in diabetic patients (p=0.004, OR=2.18, 95% confidence interval (CI) =1.29-3.70),
      but not in hypertensive patients. No association between homozygous deletion of
      GSTM1 and the development of ESRD was found in either diabetic patients or
      hypertensive patients. These results indicate that genetic variations in enzymes
      involved in free radical metabolism are associated with the development of ESRD
      in diabetes mellitus (DM) patients, and may permit the targeting of preventive
      and early intervention strategies to high-risk individuals.

PMID- 15492857
TI  - The Notch ligand, Delta-1, reduces TNF-alpha-induced growth suppression and
      apoptosis by decreasing activation of caspases in U937 cells.
AB  - The Notch signaling pathway plays an important role in the regulation of self
      renewal and differentiation of hematopoietic progenitors. Tumor necrosis factor
      (TNF)-alpha induces apoptosis through activation of caspase pathway. A
      monoblastic leukemia cell line, U937, undergoes apoptosis following stimulation
      with TNF-alpha. We found that Notch activation induced by a recombinant Notch
      ligand, Delta-1, reduced the TNF-alpha-induced growth suppression and apoptosis
      in U937 cells. As the molecular mechanism involved, we showed Delta-1 stimulation
      partially suppressed the sequential activation of caspase-8, caspase-3, and, PARP
      induced by TNF-alpha. The TNF-alpha-induced activation of c-Jun N-terminal kinase
      (JNK), p38, and NF-kappaB was not affected by Delta-1 stimulation. The cells
      needed to be exposed to Delta-1 prior to TNF-alpha stimulation to reduce the
      suppressive effect of TNF-alpha. Therefore, we thought that Delta-1 stimulation
      might reduce the expression of TNF-receptor (R) 1 and proteins to modulate the
      activation of caspases such as FLIP and XIAP. However, Delta-1 stimulation did
      not affect their expression. The precise mechanism by which Notch signaling
      suppresses caspase activation has yet to be determined. This is the first report
      to show the relationship between Notch activation and TNF-R1 signaling. The
      findings suggest possible mechanisms by which Notch activation supports cell
      survival.

PMID- 15492858
TI  - Identification of differentiation-inducing activity produced by human bone marrow
      stromal cell line LP101.
AB  - We have previously reported that human promyelocytic leukemia HL-60 cells can be
      induced to differentiate into mature granulocytes when HL-60 co-cultivated with
      human bone marrow stromal LP101 cells. In the present study, we investigated
      which factors produced by LP101 cells induce HL-60 cells to differentiate into
      mature granulocytes. The expression of the cell surface antigen CD11b on HL-60
      cells was increased after a 72-h culture with the conditioned medium (CM)
      obtained from LP101 cells. LP101 cells were observed to produce various
      cytokines, including TNF-alpha, GM-CSF and IL-6. The neutralizing antibodies
      against these cytokines partially suppressed the CM-induced differentiation of HL
      60 cells. Recombinant TNF-alpha induced the differentiation of HL-60 cells, and
      GM-CSF and IL-6 additionally enhanced the effect of TNF-alpha. When the CM was
      divided into a low molecular weight (LMW) fraction and a high molecular weight
      (HMW) fraction by ultrafiltration, the LMW fraction synergistically enhanced the
      differentiation inducible activity of TNF-alpha. These results demonstrate that
      LP101 cells induce the differentiation of HL-60 cells by producing various
      cytokines including TNF-alpha, IL-6, and GM-CSF, and that unknown low molecular
      weight factors also participate.

PMID- 15492859
TI  - Effects of leptin and leptin fragments on corticosterone secretion and growth of
      cultured rat adrenocortical cells.
AB  - Compelling evidence indicates that leptin, acting via specific receptors (Ob-Ra
      and Ob-Rb) modulates adrenocortical-cell secretion. However, the results are
      controversial, inasmuch as either secretagogue or antisecretagogue effects have
      been reported. Hence, we decided to study the effects of a 96-h incubation with
      leptin and leptin fragments 116-130, 150-167, 138-167, 93-105, 22-56 and 26-39
      (10(-8) and 10(-6) M) on the secretion and growth of cultured rat adrenocortical
      cells. Reverse transcription-polymerase chain reaction showed that control
      cultures expressed both Ob-Ra and Ob-Rb isoforms. As expected, ACTH (10(-8) M)
      raised corticosterone secretion and lowered proliferation rate of cultured cells.
      Native leptin elicited ACTH-like effects, while fragment 116-130 was ineffective.
      Leptin fragments 150-167 and 26-39 stimulated corticosterone production, and
      fragments 138-167 and 22-56 inhibited it. Fragment 93-105 exerted a dose
      dependent biphasic effect on corticosterone secretion (i.e. stimulation and
      inhibition at the concentration of 10(-8) and 10(-6) M, respectively). Leptin
      fragment 26-39 enhanced proliferation of cultured cells, while fragments 138-167
      and 22-56 were ineffective. Fragments 150-167 and 93-105 displayed proliferogenic
      and antiproliferogenic effects at the concentration of 10(-8) and 10(-6) M,
      respectively. Taken together, these findings allows us to conclude that native
      leptin and its fragments interact differently with Ob-Rs or interact with
      different Ob-R isoforms, thereby variously modulating secretion and growth of
      cultured rat adrenocortical cells.

PMID- 15492860
TI  - In vitro and in vivo anti-allergic activity of soy sauce.
AB  - Soy sauce (Shoyu) is a traditional fermented seasoning of Japan and available
      throughout the world. Polysaccharides were obtained from dialysate of Shoyu, and
      these Shoyu polysaccharides (SPS) were examined for anti-allergic activity in
      vitro and in vivo. The SPS originated from partially-degraded polysaccharides of
      soybeans by mold enzymatic hydrolyses, and Shoyu contained about 1% (w/v) SPS.
      First, the inhibitory effects of SPS on hyaluronidase, which is known to be
      related to inflammation and allergic responses, were as potent as those of an
      anti-allergic medicine, disodium cromoglycate. Second, SPS significantly
      inhibited the release of histamine from rat basophilic leukemia (RBL-2H3) cells,
      which had been induced by the antigen. Third, orally administered SPS had a
      significant suppressive effect on passive cutaneous anaphylaxis induced in the
      ears of mice. These results suggest that SPS may have anti-allergic activities,
      and soy sauce is a potentially promising seasoning for the treatment of allergic
      diseases through food.

PMID- 15492861
TI  - Quality of life improvement with soy sauce ingredients, Shoyu polysaccharides, in
      perennial allergic rhinitis: a double-blind placebo-controlled clinical study.
AB  - Soy sauce (Shoyu) is a traditional fermented seasoning of East Asian countries
      and available throughout the world. We obtained polysaccharides from raw soy
      sauce, and showed the anti-allergic activities of these Shoyu polysaccharides
      (SPS) in vitro and in vivo. The present study determined whether oral
      supplementation of SPS is an effective intervention for patients with perennial
      allergic rhinitis. In a 4-week randomized, double-blind, placebo-controlled
      parallel group study, patients with mild perennial allergic rhinitis were treated
      with 600 mg of SPS (n=11) or placebo (n=10) each day. After 4 weeks of treatment
      with SPS, a reduction in symptom scores for runny nose, sore throat, and itchy
      eyes were significantly changed from the baseline within the group (p<0.05), but
      no change in these scores was observed over 4 weeks of treatment in the placebo
      group. However, differences in the symptom scores during the study period were
      not significantly different between the groups. The total symptom score,
      calculated from the sum of individual scores, showed a significant difference
      between the 2 groups after 4 weeks of treatment (p<0.05). The efficacy of global
      symptoms score, which was defined as the adjusted mean change from baseline
      during 4 weeks of treatment, also showed a significant improvement in the SPS
      group (p<0.05). An overall evaluation of the medication's effectiveness after 4
      weeks treatment showed significant differences between the SPS- and placebo
      treated groups (p<0.05). In conclusion, SPS of soy sauce improved the quality of
      life for patients with perennial allergic rhinitis, and soy sauce would be useful
      in an anti-allergic therapy utilizing everyday foods.

PMID- 15492862
TI  - Expression of albumin in bone tissues and osteoblastic cells: involvement of
      hormonal regulation.
AB  - The expression of albumin in bone-related cells was investigated. Bone marrow
      cells and femoral-diaphyseal and -metaphyseal tissues were obtained from normal
      rat femur. Western blot analysis for protein in the lysate of bone marrow cells
      showed expression of albumin. The production of albumin was found in the bone
      marrow cells and femoral-diaphyseal and -metaphyseal tissues obtained from rat
      femur. When the femoral-diaphyseal and -metaphyseal tissues were cultured for 48
      h in a serum-free medium in vitro, albumin was greatly released into culture
      medium from the bone tissues. The expression of albumin in osteoblastic MC3T3-E1
      cells was investigated by Western blot analysis. Osteoblastic cells were cultured
      for 48 h in a serum-free medium containing either vehicle, parathyroid hormone (1
      34) (human PTH; 10(-7) M), 17beta-estradiol (10(-9) M), insulin-like growth
      factor-I (IGF-I; 10(-8) M) or zinc sulfate (10(-4) M). The production of albumin
      in osteoblastic cells was significantly enhanced in the presence of PTH, IGF-I,
      17beta-estradiol or zinc sulfate. These factors stimulated significantly the
      release of albumin from osteoblastic cells into culture medium. The effect of IGF
      I (10(-8) M) in increasing the production of albumin in osteoblastic cells was
      completely prevented in the presence of cycloheximide (10(-7) M), an inhibitor of
      protein synthesis, or 5, 6-dichloro-1-beta-D-ribofuranosyl-benzimidazole (DRB;
      10(-6) M), an inhibitor of transcriptional activity. This study demonstrates that
      albumin is expressed in bone marrow cells and osteoblastic cells, and that the
      production of albumin in osteoblastic cells is enhanced by various bone anabolic
      factors in vitro.

PMID- 15492863
TI  - Molecular and morphometric description of adipose tissue during weight changes: a
      quantitative tool for assessment of tissue texture.
AB  - The aim of this study was to evaluate the morphometric changes of adipose tissue
      of lean and obese rats as assessed by computerized image analysis (IA) system in
      experimental conditions, with different degrees of adiposity. Moreover, to
      validate measures obtained by image analysis by correlation with direct measures
      of adiposity (body weight, epididimal fat, mean fat cell size and serum leptin).
      Finally to correlate these changes to expression of genes involved in lipid
      deposition and mobilization in adipose tissue. Lean (Fa/?) and genetically obese
      (fa/fa) Zucker rats were studied. Obese rats were food-restricted or treated with
      retinoic acid (ATRA) in order to reduce body weight and fat content. Moreover,
      gene expression of two key enzymes involved in fat metabolism (HSL and DGAT) were
      assessed in adipose tissue by RT-PCR. Our results show that HSL expression in
      adipose tissue was lower in obese compared to lean rats (1.47+/-0.02 vs 0.35+/
      0.03, p<0.005) and was upregulated during food restriction in obese rats. DGAT
      expression was similar in lean and obese rats and was reduced by treatment with
      ATRA in obese rats. Tissue texture assessed by IA was significantly higher in
      lean compared to obese rats (23.2+/-0.6 vs 11.6+/-2.4%; p=0.01). Tissue structure
      highly correlated with adiposity in obese rats with different amount of body fat
      (area fraction vs epididimal fat depot: p=0.001). Distribution of measures for
      each sample, an index of spread of adipose tissue texture, as expressed by the
      standard deviation, correlated with adiposity (standard deviation vs epididimal
      fat depot: p=0.002) thus suggesting that adipose tissue texture increases its
      heterogeneity when adiposity is lower. This observation is in agreement with the
      hypothesis that the process of lipid mobilization from adipose tissue is not
      uniform, but a subpopulation of slimming adipocytes undergoes a complete release
      of their fat content while the rest of the tissue is much less affected.
      Moreover, image analysis system seems a reliable quantitative tool for assessment
      of adipose tissue texture.

PMID- 15492864
TI  - Haplotype and linkage disequilibrium analysis of the CRMP1 and EVC genes.
AB  - In this report, we present the haplotype and linkage disequilibrium (LD) pattern
      in the Collapsin Response Mediator Protein 1 (CRMP1) and Ellis-van Creveld
      syndrome (EVC) gene region. We genotyped eight different single nucleotide
      polymorphisms (SNPs) in the CRMP1 and EVC genes in 90 control individuals of
      diverse ethnicity. The minor allele frequencies ranged from 3.3-49.4%, with most
      having a frequency >25%. A total of 37 haplotypes were derived from these eight
      polymorphisms, with only one haplotype having a frequency >10%. Pairwise LD
      analysis showed a weak but significant LD between markers located about 243 kb
      apart in this region. The LD was significant between markers spaced about 208 kb
      apart in EVC, whereas no LD was found between a pair of markers located about 5
      kb apart in CRMP1. However, in general, LD correlated with the distance between
      loci. The CRMP1 and EVC genes are located near WFS1, the Wolfram syndrome type 1
      gene, in which mutations also cause low frequency sensorineural hearing loss
      (LFSNHL). The haplotypes obtained from these polymorphisms will be useful to
      track the segregation of phenotypes in families with Ellis-van Creveld syndrome,
      Weyers acrodental dysostosis, LFSNHL and Wolfram syndrome type 1.

PMID- 15492865
TI  - Implications of the evolution pattern of human T-cell leukemia retroviruses on
      their pathogenic virulence (Review).
AB  - Simian retroviruses pose a serious threat to public health, as two human
      pathogenic retroviruses, HIV and HTLV, have been already proved to originate from
      such non-human viruses. Therefore, studying their natural prevalence among wild
      non-human primates is important for planning strategies to prevent the emergence
      of additional human retroviral pathogens. This article is focused on tracing the
      origin and evolution of the human T-cell leukemia viruses HTLV-I and HTLV-II in
      comparison to that of the simian lymphotropic viruses STLV-I, STLV-II and STLV-L,
      which are phylo-genically classified into a common group called primate T
      lymphotropic viruses (PTLV). Thus, HTLV-I and STLV-I are referred to as PTLV-I
      and HTLV-II and STLV-II as PTLV-II, whereas STLV-L, which is highly divergent
      from both HTLV types, comprises a third subgroup called PTLV-L. The phylogeny of
      PTLV indicates that both, HTLV-I and HTLV-II emerged from a simian origin, but
      their subsequent evolution continued in different patterns. HTLV-I includes 6
      subtypes which evolved from STLV-I through several times of different geographic
      interspecies transmission between simian and human hosts. These repeated
      invasions to new primate species are likely to give rise to viral strains with
      increasing pathogenic potential. On the other hand, HTLV-II includes 4 subtypes
      which appear to originate from a common human ancestor virus that emerged from
      only one simian to human transmission, whereas the subsequent evolution of HTLV
      II and STLV-II strains continued separately only within the Homo sapiens and Pan
      paniscus species respectively, without repeated interspecies jumps. Such
      evolution pattern likely involves less genetic changes and selection of viral
      strains with low pathogenic virulence that could co-exist with their hosts for
      long time. These different evolution patterns can explain the much wider
      implication of HTLV-I with human clinical disorders than HTLV-II. Of note,
      however, more recently HTLV-II started spreading much more rapidly through
      intravenous drug users to many geographical regions, with a 150-350 fold higher
      mutation rate than that of its previous strictly endemic strains. This change in
      the mode of the virus spread creates a serious risk for emergence of HTLV-II
      strains with higher virulence.

PMID- 15492866
TI  - Characterization of polysaccharides from the flowers of Nerium indicum and their
      neuroprotective effects.
AB  - Degeneration of neurons is a key problem in Alzheimer's disease (AD) and
      neuroprotection is a possible way to safeguard neurons from neurodegeneration.
      Polysaccharides isolated from Chinese medicinal herbs have been investigated
      extensively for their anti-tumor and immune stimulating effects. Yet, little is
      known about the effects of polysaccharides in neurons. Recently, two pure
      polysaccharides isolated from the flowers of Nerium indicum were shown to
      stimulate proliferation and differentiation of PC12 pheochromocytoma cells, an
      effect similar to that observed from nerve growth factor. In this notion, it is
      hypothesized that polysaccharides isolated from the flowers of N. indicum could
      exhibit beneficial effects in neurons. In this study, we isolated, characterized
      and investigated two new polysaccharides from the flowers of N. indicum for their
      neuroprotective effects on neurons against serum-deprivation and beta-amyloid
      (Abeta) peptide toxicity in primary rat cortical neuronal cultures. Pretreatment
      of the polysaccharides significantly reduced the number of apoptotic neurons
      revealed by DAPI staining when neurons were exposed to serum-free medium.
      Besides, the polysaccharides could also decrease the activity of caspase-3
      triggered by Abeta peptides. Western blot analysis indicated that polysaccharides
      stimulated the phosphorylation of PDK-1 (Serine 241) and Akt (Threonine 308). In
      conclusion, the polysaccharides J2, J3 and J4 isolated from N. indicum provide a
      lead for future development of neuroprotective agent against neuronal death in
      neurodegenerative diseases and the neuroprotective mechanism may primarily rely
      on activation of Akt survival signaling pathway.

PMID- 15492867
TI  - Growth inhibitory potential of effective microorganism fermentation extract (EM
      X) on cancer cells.
AB  - The effective microorganism (EM-X) fermentation extract is derived from rice bran
      and seaweed extract. It has been shown to possess anti-oxidation activity both in
      vitro and in vivo. To our knowledge, the possible in vitro anti-cancer potential
      of EM-X has not been demonstrated. Here we showed that the double concentrate of
      EM-X (EM-X2) at concentrations of 20-30% by volume, had growth inhibitory
      activity on MDA-MB231 breast cancer cell line and K-562 chronic myelogenous
      leukaemia cell lines by [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)
      2-(4-sulfophenyl)-2-H-tetrazolium, inner salt] (MTS) assay. No characteristic
      features of apoptosis could be observed morphologically. Colony formation assay
      illustrated that both MDA-MB231 breast cancer and K-562 CML cells lost part of
      their regeneration potential after treatment with EM-X2 at 30% concentration by
      volume for 24 h. At these concentrations, only slight growth inhibitory effect
      was observed in 293 human kidney fibroblast cells and in three non-malignant bone
      marrows. Intracellular nitro blue tetrazolium (NBT) reduction assay showed that
      both MDA-MB231 breast cancer and K-562 CML cells had about 30% reduction of
      intracellular NBT after incubation with 30% of EM-X2. Increased activity of
      superoxide dismutase (SOD) could be detected from both MDA-MB231 and K-562 cell
      lines after incubating with 30% of EM-X2. Taken together, our data suggested that
      EM-X could inhibit growth and reduce the regeneration potential of cancer cells,
      possibly through its antioxidation activity.

PMID- 15492868
TI  - Targeting metastatic leiomyosarcoma by rapamycin plus gemcitabine: an intriguing
      clinical observation.
AB  - The emerging anti-cancer approach is based on combining a 'traditional' cytotoxic
      drug with a 'signaling' blocking agent. Such combination, if designed and applied
      properly, may increase selectivity towards tumor cells. The use of such
      combinations requires smart planning and choice of the drugs to be combined,
      their proper dosing as well as correct sequence and schedule of application. The
      combination of the anti-metabolite gemcitabine and the mTOR blocker, rapamycin,
      has achieved an impressive response in a patient with metastatic leiomyosarcoma.

PMID- 15492870
TI  - Identification and characterization of ARHGAP27 gene in silico.
AB  - ARHGAP1, ARHGAP2, ARHGAP3, ARHGAP4, ARHGAP5, ARHGAP6, ARHGAP7 (DLC1), ARHGAP8,
      ARHGAP9, ARHGAP10, ARHGAP12, ARHGAP13 (SRGAP1), ARHGAP14 (SRGAP2), ARHGAP15,
      ARHGAP17 (RICH1), ARHGAP18, ARHGAP19, ARHGAP20, ARHGAP21, ARHGAP22, ARHGAP23,
      ARHGAP24, ARHGAP25, ARHGAP26, STARD13 (DLC2), HA-1, GMIP, PARG1, RACGAP1, PIK3R1,
      PIK3R2, and FNBP2 genes encode Rho/Rac/Cdc42-like GTPase activating (RhoGAP)
      proteins. Here, we characterized human ARHGAP27 gene by using bioinformatics.
      Complete coding sequence of ARHGAP27 isoform 1, encoding a full-length 889-aa
      protein, was determined by assembling exon 1 (nucleotide position 143440-144096
      of AC091132.16) and most part of FLJ43547 cDNA (nucleotide position 69-3628 of
      AK125535.1). Complete coding sequence of ARHGAP27 isoform 2, encoding an N
      terminally truncated 548-aa protein, was derived from FLJ43547 cDNA. ARHGAP27
      isoform 1 consists of exons 1-17, while ARHGAP27 isoform 2 consists of exons 1B,
      and 2-17. ARHGAP27 gene encoded two isoforms due to alternative splicing of
      alternative promoter type. ARHGAP27 mRNA was expressed in germinal center B cell,
      spleen, chronic lymphocytic leukemia, pancreatic cancer, and lung cancer.
      LOC303583 (NM_ 198759.1) was the representative rat Arhgap27 cDNA. Human ARHGAP27
      showed 84.3% total-amino-acid identity with rat Arhgap27, and 39.0% total-amino
      acid identity with human ARHGAP12. ARHGAP27 and ARHGAP12 shared the common-domain
      structure, consisting of SH3, WW, PH, and RhoGAP domains. ARHGAP27 gene was
      located at human chromosome 17q21, while ARHGAP12 gene was located at human
      chromosome 10p11. ARHGAP family genes are cancer-associated genes, because their
      genetic alterations lead to carcinogenesis through the dysregulation of Rho/Rac/
      Cdc42-like GTPases. This is the first report on identification and
      characterization of the ARHGAP27 gene.

PMID- 15492869
TI  - Impaired apoptosis of lymphocytes derived from patient with decreased expression
      of caspase-8 results in Alps-like phenotype.
AB  - Human autoimmune lymphoproliferative syndrome has been described as a result of
      various mutations concerning genes encoding receptor CD95 and/or its ligand -
      CD178. However, recently, several cases with identical clinical manifestation,
      despite a normal structure of CD95 or CD178 have also been reported. In this
      study we analyzed PBMC obtained from patient with clinically overt
      lymphoproliferative disorder. Using in vitro assays as well as molecular methods
      we tested expression and biological activity of CD95 and CD178 molecules. We
      found that analyzed patient's lymphocytes displayed normal cytotoxic activity
      against CD95-bearing targets. However, CD95-dependent induction of apoptosis in
      analyzed lymphocytes was diminished, as compared to healthy control.
      Surprisingly, the molecular studies did not reveal any abnormalities in structure
      of patient-derived CD95 receptor molecule. Therefore, expression of other factors
      involved in CD95-mediated signaling pathway was estimated using RNase protection
      assay. The expression of FADD was comparable to that of healthy control. However,
      it has been found that patient-derived lymphocytes expressed reduced amount of
      caspase-8 mRNA, as compared to control subject cells. This report confirms
      previous observations that lymphoproliferative disorder could be associated not
      only with CD95 and/or CD178 mutations, but also with dysfunction of other
      components of apoptosis induction pathway. However, the detailed molecular
      mechanism of observed abnormalities in caspase-8 expression remains to be
      elucidated.

PMID- 15492871
TI  - Characterization of human FOXN4 gene in silico.
AB  - Forkhead-box (FOX) superfamily genes are implicated in carcinogenesis through
      gene amplification, retroviral integration and chromosomal translocation. FOX
      superfamily genes within the human genome are classified into 17 or 18 families,
      designated FOX# (# is alphabet A-Q or R). FOXN1, FOXN2 (HTLF), FOXN3 (CHES1),
      FOXN4, FOXN5 (FOXR1) and FOXN6 (FOXR2) genes constitute the FOXN gene family.
      Here, we characterized human FOXN4 gene by using bioinformatics. FOXN4 gene at
      human chromosome 12q24.12 was found to encode three isoforms. FOXN4 isoform 1
      (representative transcript), encoding a 518-aa protein, consists of exons 1-10.
      FOXN4 isoform 2 (NM_ 213596.1), encoding a 337-aa protein, consists of exons 1,
      2, 7v, 8-10. FOXN4 isoform 3, encoding a 314-aa protein, consists of exons 1-5, 7
      10. Codon 205-518 of isoform 1 was conserved in isoforms 2 and 3. FOXN4 mRNA was
      expressed in testis, embryonic stem (ES) cells, uterus tumors, and
      leiomyosarcoma. FOXN4 was most homologous to FOXN1 among human FOXN family
      members. FOXN4 and FOXN1 showed 41.3% total-amino-acid identity. FOX domain
      (codon 192-305 of FOXN4) was well conserved among mammalian FOXN family members.
      FN14 domain (codon 367-456 of FOXN4) was identified as the novel domain conserved
      among FOXN4 and FOXN1 orthologs. FOXN4 and FOXN1 orthologs were found to share
      the common domain structure, consisting of FOX and FN14 domains. This is the
      first report on comprehensive characterization of the human FOXN4 gene as well as
      on identification of the FN14 domain.

PMID- 15492872
TI  - [The educational counselor in pneumology internship].

PMID- 15492873
TI  - [The global smoking prevention programme of Braga].
AB  - In spite of its negative impacts on health, in the society, in the economy and in
      the environment, smoking is a behaviour spread national and internationally. The
      data collected in 1999 by the Health National Inquire about smoking prevalence in
      people from 15 and over, in Portugal mainland, show that 29.3% of men and around
      7.9% of women were daily smokers, which means a total of 1,626,597 smokers
      (1,248,212 men and 378,385 women). If we analyse the data from other sources
      (Health National Inquires and Eurobarometer) we can see that the tobacco epidemy
      is growing among both gender but in a particulary alarming way in the female
      group. It is necessary and urgent to take some primary prevention measures
      especially addressed to young people and women and at the same time give all the
      smokers the chance of treatment. Bearing in mind the idea of the Ecologist
      Movement "thinking globally, acting locally" we defend the implementation of
      global but local actions as the best approach to control smoking. In this article
      we describe the state and the trends of smoking in Portugal as well as The Global
      Prevention Programme of Tobacco Consumption in Braga (North of Portugal). This
      action plan is intended to solve in a decisive way the tobacco consumption in
      Braga and at the same time to be taken as an example for the elaboration of a
      National Plan for Prevention the Tobacco Consumption.

PMID- 15492874
TI  - [Plasma concentration of lidocaine during bronchoscopy].
AB  - Lidocaine is commonly used for local anesthesia during fiberoptic bronchoscopy
      (FOB). It has been suggested that the total dose of lidocaine should be limited
      to 300-400 mg (or < 8.2 mg/kg). Lidocaine toxicity is directly correlated with
      its concentration in the blood and a threshold above which the side effects
      become more likely has been put at a plasma level of 5 microg/ml. The aim of our
      study was to determine plasmatic lidocaine concentrations (PLC), how often the
      PLC fall into the potentially toxic range and its correlation with adverse
      reactions. PLC were recorded in 30 patients undergoing FOB. Lidocaine was
      administered as a 2% gel, 10% spray and 2% solution. Venous blood samples were
      taken before the beginning of local anesthesia and at 20, 30 and 40 min
      thereafter. The mean total amount of lidocaine administered was 746.3 +/- 159.5
      mg (11.6 +/- 3.1 mg/kg). Before the beginning of anesthesia, no significant
      levels of lidocaine were measurable in the patients. PLC were 3.2 +/- 1.7 (g/ml
      at 20 min., 3.3 +/- 1.7 microg/ml at 30 min. and 3.0 +/- 1.5 microg/ml at 40 min.
      The PLC exceeded toxic levels in 6 patients, but no complications were observed.
      Our data show that although the amount of lidocaine used in this study exceeded
      the recommended highest dose, no subjects had signs of toxicity. A maximum dose
      of lidocaine for topical anesthesia should be determined despite the fact that an
      average total dose superior to 400 mg appears to be safe in patients undergoing
      FOB.

PMID- 15492875
TI  - [Risk predictive factors for the appearing of a second primary lung neoplasms in
      104 patients].
AB  - OBJECTIVES: The objective of our study was to identify the risks factors for the
      de development of a second pulmonary primary cancer. METHODS: It was a primary,
      observational, multicentric and retrospective study with 104 patients from the
      Cancer National Institute and the Antonio Pedro Universitary Hospital, in Rio de
      Janeiro, Brazil. RESULTS: The sites of primary tumors were: head and neck
      (56.7%); with laryngeal carcinoma (42.4%); lungs (15.5%); bladder (8.6%); uterine
      cervix (7.6%); stomach (4.8%); others (6.8%). Male patients represented 84.6%.
      Average age 56.7 +/- 10.7 years, with a coefficient of variation 18.8%. Among the
      patients 91.4% were smokers and 92.0% were alcohol consumers. Multiple logistic
      regression model: site of primary tumor (OR:8.22; CI 95% - 2.21 to 30.56; p =
      0,0017); specific histologic of primary cancer (OR:0.21; IC 95% : 0.04 to 0.99; p
      = 0.0498); sex (OR: 0.25; CI 95% : 0.03 to 1.81; p = 0.1711); age (OR: 0.98; CI
      95%: 0.92 to 1.04; p = 0.6318); smoking (OR: 2.80; CI 95%: 0.44 to 17.55; p =
      0.2711) and alcohol consumption (OR:0.76; CIIC 95%: 0.19 to 2.95; p = 0.6964).
      Adjusted model: odds ratio of the site of the primary tumor was 4.14, ; CI 95%;
      from 1.36 and 12.78 and p = 0.0123 (p < 0.05). Accuracy or the model: 82. 69%.
      CONCLUSION: In this study teh site of the primary tumor was the only predictor of
      risk for the second pulmonary primary cancer.

PMID- 15492876
TI  - [Pleurodesis].
AB  - Pleurodesis is a way of inducting an inflammatory process in the pleural surface
      in order to create the closure of the pleural space. The exact mechanism isn't
      completely understood and there is still a great deal of controversy concerning
      pleurodesis. Pleurodesis can be achieved by introduction of a sclerosant agent
      trough a chest tube into the pleural space, by medical thoracoscopy, by surgical
      thoracoscopy or by thoracotomy. The principal sclerosant agents are talc and
      tetracycline. The indications for pleurodesis are malignant recurrent pleural
      effusion, primary recurrent pneumothorax, secondary pneumothorax and benign
      pleural effusion resistant to medical treatment. There are, although, some
      contraindications to performing it. Serious complications of pleurodesis are rare
      and depend on the technique and agent used. The method of choice for pleurodesis
      is related to the experience and technical facilities available. The author
      presents a review about pleurodesis.

PMID- 15492877
TI  - [Asthma concepts and epidemiological tools for prevalence researches].
AB  - INTRODUCTION: Asthma, as a multifatorial disease, with high prevalence and
      frequent recurrence, attack people, independently of age, sex and geographical
      area. Because of lack of consensus about the definition of asthma, many
      questionnaires have been developed to standardize epidemiological criteria of
      suspicion and diagnosis. Among them, the European Community Respiratory Health
      Survey (ECRHS) is an important tool for prevalence studies on adults aged from 20
      to 44 years old, that represented a methodological improvement of epidemiological
      surveys, turning them comparable about time and place. The objectives of this
      article are to comment the evolution of asthma concepts and its repercussion on
      epidemiological surveys, as well as to chronicle the tools used on these surveys,
      emphasizing the importance of ECRHS and presenting epidemiological data of asthma
      on 351 universitary hospital servers at Recife City -- Pernambuco -- Brazil.

PMID- 15492878
TI  - [Nonspecific interstitial pneumonitis: a clinicopathologic entity, histologic
      pattern or unclassified group of heterogeneous interstitial pneumonitis?].
AB  - Nonspecific interstitial pneumonitis (NSIP) initially described by Katzenstein
      and Fiorelli in 1994, seems to be a distinct clinicopathologic entity among
      idiopathic interstitial pneumonitis (IIP). Besides different histologic features
      from other IIP, NSIP is characterized by a better long-term outcome, associated
      with a better steroids responsiveness than idiopathic pulmonar fibrosis (IPF),
      where usually were included. Thus, differentiating NSIP from other IIP, namely
      IPF is very significant, since it has important therapeutic and prognostic
      implications. NSIP encloses different pathologies, namely those with inflammatory
      predominance (cellular subtype) or fibrous predominance (fibrosing subtype). NSIP
      is reviewed and discussed by the authors, after two clinical cases description.

PMID- 15492879
TI  - [Cryptogenic organizing pneumonia -- case report].
AB  - Cryptogenic organizing pneumonia (COP) is one of the new recognized histological
      patterns of idiopathic interstitial pneumonias, in witch no cause or association
      is identified. Idiopathic bronchiolitis obliterans-organizing pneumonia (BOOP) is
      a synonymous. This rare entity is characterized by involvement of alveoli and
      bronchioles, which are filled by intraluminal polyps of fibroblastic tissue
      (Masson bodies). The clinical presentation often mimics that of community
      acquired pneumonia. Persistent non-productive cough, dyspnoea with exertion and
      weight loss are common features, and in one-half of the cases the onset is
      heralded by a flu-like syndrome. Definitive diagnosis depends on histological
      data, and video-assisted thoracoscopic (VAT) has become the established
      technique. Spontaneous recovery is rare; corticosteroid therapy provides cure in
      two thirds of cases. The authors present a case of a patient whose lung biopsy by
      VAT confirmed the diagnosis. She was treated with corticoids without recurrence
      in a two year follow-up.

PMID- 15492880
TI  - [Acute eosinophilic pneumonia associated with acute respiratory distress
      syndrome: case report].
AB  - The Authors present a case of acute eosinophilic pneumonia (AEP) associated with
      severe acute respiratory distress syndrome in a previously healthy young adult,
      medicated with nitrofurantoin. AEP must be included in the differential diagnosis
      of community adquired pneumonia, as well as a cause of acute respiratory distress
      syndrome; its diagnosis is suggested by the presence of eosinophilic alveolitis
      in bronchoalveolar lavage fluid. The early diagnosis of AEP and corticosteroid
      therapy may be lifesaving.

PMID- 15492883
TI  - Cross correlation by neurons of the medial superior olive: a reexamination.
AB  - Initial analysis of interaural temporal disparities (ITDs), a cue for sound
      localization, occurs in the superior olivary complex. The medial superior olive
      (MSO) receives excitatory input from the left and right cochlear nuclei. Its
      neurons are believed to be coincidence detectors, discharging when input arrives
      simultaneously from the two sides. Many current psychophysical models assume a
      strict version of coincidence, in which neurons of the MSO cross correlate their
      left and right inputs. However, there have been few tests of this assumption.
      Here we examine data derived from two earlier studies of the MSO and compare the
      responses to the output of a computational model. We find that the MSO is not an
      ideal cross correlator. Ideal cross correlation implies a strict relationship
      between the precision of phase-locking of the inputs and the range of ITDs to
      which a neuron responds. This relationship does not appear to be met. Instead,
      the modeling implies that a neuron responds over a wider range of ITDs than
      expected from the inferred precision of phase-locking of the inputs. The
      responses are more consistent with a scheme in which the neuron can also be
      activated by the input from one side alone. Such activation degrades the tuning
      of neurons in the MSO to ITDs.

PMID- 15492884
TI  - The role of spectral and temporal cues in voice gender discrimination by normal
      hearing listeners and cochlear implant users.
AB  - The present study investigated the relative importance of temporal and spectral
      cues in voice gender discrimination and vowel recognition by normal-hearing
      subjects listening to an acoustic simulation of cochlear implant speech
      processing and by cochlear implant users. In the simulation, the number of speech
      processing channels ranged from 4 to 32, thereby varying the spectral resolution;
      the cutoff frequencies of the channels' envelope filters ranged from 20 to 320
      Hz, thereby manipulating the available temporal cues. For normal-hearing
      subjects, results showed that both voice gender discrimination and vowel
      recognition scores improved as the number of spectral channels was increased.
      When only 4 spectral channels were available, voice gender discrimination
      significantly improved as the envelope filter cutoff frequency was increased from
      20 to 320 Hz. For all spectral conditions, increasing the amount of temporal
      information had no significant effect on vowel recognition. Both voice gender
      discrimination and vowel recognition scores were highly variable among implant
      users. The performance of cochlear implant listeners was similar to that of
      normal-hearing subjects listening to comparable speech processing (4-8 spectral
      channels). The results suggest that both spectral and temporal cues contribute to
      voice gender discrimination and that temporal cues are especially important for
      cochlear implant users to identify the voice gender when there is reduced
      spectral resolution.

PMID- 15492885
TI  - Linopirdine blocks alpha9alpha10-containing nicotinic cholinergic receptors of
      cochlear hair cells.
AB  - Studies of the electrophysiological response to acetylcholine (ACh) in mammalian
      outer hair cells (OHCs) are hindered by the presence of a large potassium
      current, I(K,n), most likely mediated by channels containing the KCNQ4 subunit.
      Since I(K,n) can be blocked by linopirdine, cholinergic effects might be better
      revealed in the presence of this compound. The aim of the present work was to
      study the effects of linopirdine on the ACh-evoked responses through
      alpha9alpha10-containing native and recombinant nicotinic cholinergic receptors.
      Responses to ACh were blocked by linopirdine in both OHCs and inner hair cells
      (IHCs) of rats at postnatal days 21-27 (OHCs) and 9-11 (IHCs). In addition,
      linopirdine blocked responses of recombinant alpha9alpha10 nicotinic cholinergic
      receptors (nAChRs) in a concentration-dependent manner with an IC(50) of 5.2
      microM. Block by linopirdine was readily reversible, voltage independent, and
      surmountable at high concentrations of ACh, thus suggestive of a competitive type
      of interaction with the receptor. The present results contribute to the
      pharmacological characterization of alpha9alpha10-containing nicotinic receptors
      and indicate that linopirdine should be used with caution when analyzing the
      cholinergic sensitivity of cochlear hair cells.

PMID- 15492886
TI  - Differences between the negatively activating potassium conductances of Mammalian
      cochlear and vestibular hair cells.
AB  - Cochlear and type I vestibular hair cells of mammals express negatively
      activating potassium (K(+)) conductances, called g(K,n) and g(K,L) respectively,
      which are important in setting the hair cells' resting potentials and input
      conductances. It has been suggested that the channels underlying both
      conductances include KCNQ4 subunits from the KCNQ family of K(+) channels. In
      whole-cell recordings from rat hair cells, we found substantial differences
      between g(K,n) and g(K,L) in voltage dependence, kinetics, ionic permeability,
      and stability during whole-cell recording. Relative to g(K,L), g(K,n) had a
      significantly broader and more negative voltage range of activation and activated
      with less delay and faster principal time constants over the negative part of the
      activation range. Deactivation of g(K,n) had an unusual sigmoidal time course,
      while g(K,L) deactivated with a double-exponential decay. g(K,L), but not g(K,n),
      had appreciable permeability to Cs(+). Unlike g(K,L), g(K,n)'s properties did not
      change ("wash out") during the replacement of cytoplasmic solution with pipette
      solution during ruptured-patch recordings. These differences in the functional
      expression of g(K,n) and g(K,L) channels suggest that there are substantial
      differences in their molecular structure as well.

PMID- 15492887
TI  - A comparative study of Eya1 and Eya4 protein function and its implication in
      branchio-oto-renal syndrome and DFNA10.
AB  - Allele variants of EYA1 and EYA4, two members of the vertebrate Eya gene family,
      underlie two types of inherited human deafness, branchio-oto-renal (BOR) syndrome
      and DFNA10, respectively. To clarify how mutations in these two genes and their
      encoded proteins impact the normal biology of hearing, we completed a number of
      functional studies using the yeast-two-hybrid system. We verified that bait
      constructs of the homologous region ( Eya1HR and Eya4HR) interact with Six1 prey
      constructs, although no interaction with Dach1 prey was demonstrable. To compare
      interaction affinities, we evaluated alpha-galactosidase activity after
      cotransformation of Eya1HR/Six1 and Eya4HR/Six1 and found that the latter
      interaction was weaker. By immunofluorescence staining, we showed Eya4HR
      localization to the cytoplasm. After coexpression of Six1, Eya4HR was
      translocated to the nucleus. Results with Eya1HR were similar. Translation of
      mutant constructs ( Eya4HR(R564X) and Eya1HR(R539X)) could not be demonstrated.
      Using dual Eya-containing constructs (with two wild-type alleles or wild-type and
      mutant alleles), we confirmed no translation of the mutant allele, even if the
      mutation was nontruncating. These results are consistent with clinical data and
      implicate haploinsufficiency as the cause of BOR syndrome and DFNA10.

PMID- 15492888
TI  - Topographic spread of inferior colliculus activation in response to acoustic and
      intracochlear electric stimulation.
AB  - The design of contemporary multichannel cochlear implants is predicated on the
      presumption that they activate multiple independent sectors of the auditory nerve
      array. The independence of these channels, however, is limited by the spread of
      activation from each intracochlear electrode across the auditory nerve array. In
      this study, we evaluated factors that influence intracochlear spread of
      activation using two types of intracochlear electrodes: (1) a clinical-type
      device consisting of a linear series of ring contacts positioned along a silicon
      elastomer carrier, and (2) a pair of visually placed (VP) ball electrodes that
      could be positioned independently relative to particular intracochlear
      structures, e.g., the spiral ganglion. Activation spread was estimated by
      recording multineuronal evoked activity along the cochleotopic axis of the
      central nucleus of the inferior colliculus (ICC). This activity was recorded
      using silicon-based single-shank, 16-site recording probes, which were fixed
      within the ICC at a depth defined by responses to acoustic tones. After
      deafening, electric stimuli consisting of single biphasic electric pulses were
      presented with each electrode type in various stimulation configurations
      (monopolar, bipolar, tripolar) and/or various electrode orientations (radial, off
      radial, longitudinal). The results indicate that monopolar (MP) stimulation with
      either electrode type produced widepread excitation across the ICC. Bipolar (BP)
      stimulation with banded pairs of electrodes oriented longitudinally produced
      activation that was somewhat less broad than MP stimulation, and tripolar (TP)
      stimulation produced activation that was more restricted than MP or BP
      stimulation. Bipolar stimulation with radially oriented pairs of VP ball
      electrodes produced the most restricted activation. The activity patterns evoked
      by radial VP balls were comparable to those produced by pure tones in normal
      hearing animals. Variations in distance between radially oriented VP balls had
      little effect on activation spread, although increases in interelectrode spacing
      tended to reduce thresholds. Bipolar stimulation with longitudinally oriented VP
      electrodes produced broad activation that tended to broaden as the separation
      between electrodes increased.

PMID- 15492890
TI  - [Papillary muscle rupture due to cardiac contusion].

PMID- 15492889
TI  - Posture, head stability, and orientation recovery during vestibular regeneration
      in pigeons.
AB  - Compensatory behavior such as oculomotor, gaze, and postural responses that occur
      during movement largely depend upon a functioning vestibular system. In the
      present study, the initial loss and subsequent recovery of postural and head
      stability in pigeons undergoing vestibular regeneration were examined. Adult
      pigeons were trained to manipulate a straight run chamber to peck an illuminated
      key for fluid reward. Six behavioral measures assessing performance, posture, and
      head stability were quantified. These included run latency, steps (walking), path
      negotiation (lane changes), gaze saccades, head bobs, and head shakes. Once
      normative values were obtained for four birds, complete lesion of all receptor
      cells and denervation of the epithelia in the vestibular endorgans were produced
      using a single intralabyrinthine application of streptomycin sulfate. Each bird
      was then tested at specific times during regeneration and the same behavioral
      measures examined. At 7 days post-streptomycin treatment (PST), all birds
      exhibited severe postural and head instability, with tremors, head shakes,
      staggering, and circling predominating. No normal trial runs, walking, gaze
      saccades, or head bobs were present. Many of these dysfunctions persisted through
      3-4 weeks PST. Gradually, tremor and head shakes diminished and were replaced
      with an increasing number of normal head bobs during steps and gaze saccades.
      Beginning at 4 weeks PST, but largely inaccurate, was the observed initiation of
      directed steps, less staggering, and some successful path negotiation. As
      regeneration progressed, spatial orientation and navigation ability increased
      and, by 49 days PST, most trials were successful. By 70 days PST, all birds had
      recovered to pretreatment levels. Thus, it was observed that ataxia must subside,
      coincident with normalized head and postural stability prior to the recovery of
      spatial orientation and path navigation recovery. Parallels in recovery were
      drawn to hair cell regeneration and afferent responsiveness, as inferred from
      present results and those in other investigations.

PMID- 15492891
TI  - [Does central vagus tone play a decisive role in myocardial ischemia?].

PMID- 15492893
TI  - The Brugada syndrome. Its relevance to paediatric practice.
AB  - The diagnostic and therapeutic aspects of Brugada syndrome, one of the important
      genetic arrhythmias which causes sudden cardiac death in young people, and the
      relevance of this diagnostic entity to the paediatric population are briefly
      summarised. The role of diagnostic testing (genetic, pharmacologic and invasive
      electrophysiologic) for establishing the diagnosis and for risk stratification
      are discussed. Finally, while the implantable defibrillator is the only therapy
      of proven effectiveness in preventing sudden cardiac death, alternative therapies
      which are being considered (pharmacologic, hormonal and catheter ablation) are
      overviewed. The aim of this manuscript is to raise the awareness among doctors
      caring for young patients to the possibility of Brugada syndrome in patients
      presenting with potentially life-threatening symptoms of syncope or near-miss
      sudden death, and in index patients with a similar family history.

PMID- 15492892
TI  - On the genesis of myocardial ischemia.
AB  - About three quarters of myocardial ischemic events are triggered by the autonomic
      nervous system. The pathognomonic constellation is a combination of an almost
      complete withdrawal of tonic vagal activity with increased sympathetic activity.
      The reduction of tonic vagal activity, which is characteristic for ischemic heart
      disease, and the acute withdrawal of vagal drive preceding the onset of ischemia
      are not dependent on coronary artery disease. In this paper, the
      pathophysiological steps that lead from sympathetic-parasympathetic imbalance to
      myocardial ischemia shall be discussed. A considerable increase of aerobic
      glycolysis within the myocardium as a result of the autonomic imbalance is of
      special importance in this process.

PMID- 15492894
TI  - Acute and long-term outcome after coronary artery perforation during percutaneous
      coronary interventions.
AB  - BACKGROUND: Coronary artery perforation is a rare but serious complication of
      percutaneous coronary interventions (PCI). METHODS: We reviewed our database for
      cases of overt coronary perforation during PCI procedures. Hospital charts,
      procedural reports, and coronary angiograms of these patients were reviewed, with
      particular emphasis on mechanisms of perforation, management of the complication,
      and clinical outcome. RESULTS: Between 01/1998 and 12/2003, a total of 19 cases
      (mean age: 66+/-8 years, 13 male) of coronary perforation occurred during 6433
      PCI procedures performed within this period (incidence: 0.3%). In 12/19 (63%)
      cases, perforation occurred during recanalisation procedures of chronic total
      occlusions of coronary arteries. In all but one patient, non-surgical management
      was attempted: 2 out of 19 (11%) patients were treated conservatively by reversal
      of heparin anticoagulation. Prolonged balloon inflation at the perforation site
      was applied in 10/19 (53%) patients. Six (32%) patients received stents (5 of
      them received covered stentgrafts), 3 (16%) patients developed cardiac tamponade
      requiring percardiocentesis, and only 2 (11%) patients underwent bailout surgical
      repair. There were 2 (11%) deaths early after the procedure. CONCLUSION: Coronary
      perforation during PCI is a rare complication, but is associated with significant
      morbidity and mortality. In the majority of patients, non-surgical management is
      both feasible and associated with a high success-rate.

PMID- 15492896
TI  - [Hemorrhagic nonspecific pericardial effusion as an initial symptom of
      angiosarcoma of the right heart].
AB  - HISTORY: A 45-year old woman presented at our hospital with intermittent fever in
      the last three weeks and progressive exertional dyspnea. In addition she suffered
      from physical asthenia. Seven months ago the patient was treated for symptomatic
      pericardial effusion in our clinic. INVESTIGATIONS: Physical examination revealed
      a pale skin color, epigastric pain on palpation and intense exertional dyspnea.
      Laboratory tests indicated microcytic anemia and high levels of LDH and CRP. The
      diagnosis of a large tumor of the right atrium and ventricle was based on the
      transthoracic echocardiogram and thoracic CT scan. The extent of the right atrial
      and ventricular mass of 9 x 8 cm was detected by trans-esophageal
      echocardiography. The thoracic and abdominal CT scan showed multiple nodular
      infiltrates in the basal lung fields and a cystic tumorous mass in the liver.
      DIAGNOSIS: The tumor developed in the short time of 7 months. Half a year ago,
      the transthoracic echocardiographic exam showed pericardial effusion with normal
      cardiac size, normal left ventricular function and no evidence of right
      ventricular outflow obstruction. No cardiac masses were observed. At that time
      pericardiocentesis was performed, but the pericardial fluid was cytologically
      negative for tumor cells. The diagnosis of angiosarcoma was made after surgical
      excision of the tumor and histological examination. There was only the
      possibility of a palliative therapy, because of the existence of pulmonary and
      liver metastases. CONCLUSIONS: Primary malignant cardiac tumors are rare and
      their prognosis is very poor. The heart angiosarcoma is often disseminated into
      the lungs and the liver at the time of clinical presentation. This case indicates
      that hemorrhagic nonspecific pericardial effusion, negative for tumor cells, can
      appear any time before a heart angiosarcoma is detectable by echocardiography.

PMID- 15492895
TI  - Stroke volume and mitral annular velocities. Insights from tissue Doppler
      imaging.
AB  - The aim of this study was to assess the impact of stroke volume (SV) on mitral
      annular velocities derived from tissue Doppler imaging (TDI). To this end,
      conventional echocardiographic variables and TDI derived mitral annular
      velocities (S', E', A') were obtained in 14 patients (pts) with increased SV (due
      to primary mitral (n=12) (ISV group)), in 41 pts with reduced SV (due to ischemic
      (n=27) or dilated cardiomyopathy (n=9) or hypertensive heart disease (n=5) (RSV
      group)) and 29 asymptomatic controls with normal SV (CON group). Systolic (S')
      and early diastolic (E') mitral annular velocities were elevated in the ISV group
      in the comparison to the CON group, but were significantly reduced in the RSV
      group. Late diastolic annular velocities (A') did not differ between the ISV and
      the CON group, but were lowest in the RSV group. On simple linear regression
      analysis, SV was significantly related to S' (r=0.74, p<0.001), to E' (r=0.74,
      p<0.001) and to A' (r=0.43, p<0.01). On multiple regression analysis, SV was a
      stronger independent predictor of S' and E' than conventional systolic or
      diastolic echocardiographic variables. Thus, stroke volume has a significant
      impact on TDI derived systolic (S') and early diastolic (E') mitral annular
      velocities. This should be considered, when TDI is used in the evaluation of LV
      performance or in the estimation of filling pressures.

PMID- 15492897
TI  - [Implantation of a biventricular pacing system via a persistent left-sided
      superior vena cava].
AB  - Cardiac resynchronization therapy by multisite biventricular pacing presents an
      additive therapeutic option in the treatment of severe heart failure.
      Biventricular pacemaker implantation is challenging in patients with persistent
      left superior vena cava. We describe in this case report the implantation of a
      biventricular pacemaker using a left-sided approach in a patient with persistent
      left superior vena cava.

PMID- 15492898
TI  - A novel implantation technique for closure of an atypical fenestration connecting
      the right atrial appendage to an extracardiac conduit by use of a 15 mm Helex
      device in a patient with total cavopulmonary connection.
AB  - We report on a 7-years old patient after total cavopulmonary anastomosis with an
      extracardiac conduit. An atypical fenestration was created during the operation
      connecting the right atrial appendage to the extracardiac conduit. Because of
      arterial desaturation, the fenestration connecting the anterior wall of the
      extracardiac conduit to the posterior wall of the right atrial appendage was
      successfully occluded with a 15 mm Helex device by use of a modified implantation
      technique.

PMID- 15492899
TI  - Paradoxical coronary embolism causing non-ST segment elevation myocardial
      infarction in a case of pulmonary embolism.
AB  - We describe the case of a 61-year-old woman who simultaneously suffered a
      pulmonary embolism and a myocardial infarction due to paradoxical coronary artery
      embolism. Transesophageal echocardiography with injection of agitated
      hydroxyethyl starch revealed a patent foramen ovale. Thrombophlebistis of the
      left saphenous vein with extension of thrombus into the femoral vein could be
      identified as the source of embolism. Paradoxical coronary embolism is an
      underrecognized cause of MI. Diagnosis is particularly difficult, when MI and PE
      coincide, because of the similarity in clinical signs and symptoms of both
      entities. A high level of clinical suspicion and echocardiography, especially if
      performed soon after presentation, can be the clue to early diagnosis of PDE.

PMID- 15492900
TI  - [Position document on quality assurance in invasive cardiology. Are minimum
      numbers in percutaneous coronary angioplasty evidence based?].

PMID- 15492901
TI  - [Minimum number regulation. A comment by the leadership of the German Society of
      Cardiology].

PMID- 15492905
TI  - Composition of the lipids of Nanoarchaeum equitans and their origin from its host
      Ignicoccus sp. strain KIN4/I.
AB  - The contents and nature of the membrane lipids of Nanoarchaeum equitans and
      Ignicoccus sp. strain KIN4/I, grown at 90 degrees C, and Ignicoccus sp. strain
      KIN4/I, cultivated at its lowest and highest growth temperatures (75 degrees C
      and 95 degrees C) were analyzed. Both organisms contained very simple and
      qualitatively identical assemblages of glycerol ether lipids, showing only
      differences in the amounts of certain components. LC-MS analyses of the total
      lipid extracts revealed that archaeol and caldarchaeol were the main core lipids.
      The predominant polar headgroups consisted of one or more sugar residues attached
      either directly to the core lipid or via a phosphate group. GC-MS analyses of
      hydrolyzed total lipid extracts revealed that the co-culture of N. equitans and
      Ignicoccus sp. strain KIN4/I, as well as Ignicoccus sp. strain KIN4/I grown at 90
      degrees C, contained phytane and biphytane in a ratio of approximately 4:1.
      Purified N. equitans cells and Ignicoccus sp. strain KIN4/I cultivated at 75
      degrees C and 95 degrees C had a phytane to biphytane ratio of 10:1. Sugar
      residues were mainly mannose and small amounts of glucose. Consistent 13C
      fractionation patterns of isoprenoid chains of N. equitans and its host indicated
      that the N. equitans lipids were synthesized in the host cells.

PMID- 15492906
TI  - [Universal hearing screening in newborns. Recommendations for organizing and
      conducting universal hearing screening for congenital hearing loss in Germany].
AB  - The Interdisciplinary Consensus Conference for Newborn Hearing Screening (IKKNHS)
      has worked out joint recommendations for universal hearing screening of newborns.
      In the consensus paper, 11 professional associations and scientific societies in
      the fields of gynecology and obstetrics, ENT, pediatrics, and phoniatrics and
      pedaudiology came to an agreement on how to implement newborn hearing screening
      in Germany. The paper deals with the following topics: goals of universal newborn
      hearing screening, target group of hearing screening, schedule for screening,
      personnel involved in the screening program, technologies and framework
      conditions of hearing screening, documentation, continuous quality control of
      screening, confirmation diagnostics for conspicuous test subjects, motivation to
      take part in screening, information on newborn hearing screening, tracking,
      various infrastructural situations in urban and rural regions, follow-up care, in
      patient vs. out-patient screening, cost factors of screening, reporting children
      with permanent hearing loss to the German Central Registry for hearing loss in
      children.

PMID- 15492907
TI  - Drug-induced hepatitis, drug-induced autoimmunity or classical autoimmune
      hepatitis: how can we differentiate?

PMID- 15492908
TI  - Cardiovascular problems in cirrhotic patients.
AB  - Cardiovascular disease associations with chronic liver disease are identified.
      The effect of these cardiovascular diseases on the natural history of the
      underlying liver disease is considered. Their recognition and management is
      important in the long term care of patients with chronic liver disease,
      especially those being considered for liver transplantation.

PMID- 15492909
TI  - Lichen planus and HCV infection in Turkish patients.
AB  - BACKGROUND/AIMS: A relation between hepatitis C virus (HCV) infection with lichen
      planus (LP) has been reported in the literature but remains controversial. To
      find out the prevalence of HVC infection among patients with LP. METHODS: Forty
      one cases of LP diagnosed at the Dermatology Clinic of our hospital between March
      1995 and May 1996 were evaluated (22 men and 19 women; mean age 41.6 years). They
      were screened for the presence of HBsAg, anti HBs, and anti-HCV by ELISA and HCV
      RNA by nested polymerase chain reaction (PCR). Blood donors registered in Ankara
      University Ibni Sina Hospital Blood Bank were used as a control group. RESULTS:
      Of the 41 LP patients, 2 (4.8%) had anti-HCV positivity together with HCV-RNA
      positivity. Twelve patients (29.2%) had anti-HBs and 3 patients (7.3%) had HBsAg
      positivity. In blood donors, anti-HCV positivity prevalence was 2.5%.
      CONCLUSIONS: The results of this study suggest that no relationship exists
      between hepatitis C virus infection and lichen planus among Turkish patients.

PMID- 15492910
TI  - Efficacy of five days of subcutaneous octreotide treatment after sclerotherapy in
      preventing rebleeding from esophageal varices.
AB  - BACKGROUND/AIMS: Acute variceal bleeding is the most severe consequence of portal
      hypertension. Mortality due to bleeding among cirrhotic patients is high; between
      30 and 50% die within six weeks of the first bleeding episode. This dismal
      outcome has led to attempts both to stop acute bleeding and to prevent
      rebleeding. The aim of this study was to investigate the efficacy of subcutaneous
      octreotide treatment, administered after emergency sclerotherapy, in preventing
      rebleeding of esophageal varices METHODS: After a bolus injection of 50 microgram
      octreotide, 34 patients, forming the standard therapy (ST) group, received
      octreotide infusion at a rate of 50 microgram/h until endoscopic sclerotherapy
      performed within 36 hours. The same procedure was applied to another 27 patients
      in the maintenance therapy (MT) group in which octreotide was given at 100
      microgram/8h via subcutaneous (sc) route after sclerotherapy for five days. In
      both groups, sclerotherapy was repeated on the 5th-7th day. Patients were
      followed for three weeks for rebleeding. RESULTS: Nine patients rebled in the ST
      group but only one patient bled in the MT group (3.7% vs. 26.5% vs. 3.7%;
      p<0.05). Transfusion requirement and duration of hospitalization period were
      similar in both groups. CONCLUSIONS: This study suggests that maintenance
      subcutaneous octreotide therapy is effective in controlling rebleeding episodes.

PMID- 15492911
TI  - Endoscopic treatment of primary sclerosing cholangitis.
AB  - BACKGROUND/AIMS: Dominant stricture of an extrahepatic bile duct is responsible
      for symptoms and an exacerbation of cholestasis in 15-20% of patients with
      primary sclerosing cholangitis. The aim of this study was to evaluate the
      efficacy and safety of endoscopic treatment in this selected patient group.
      METHODS: Retrospectively, we evaluated 16 patients who were treated
      endoscopically due to elevation of serum biochemical liver tests and symptoms
      which were attributable to dominant bile duct strictures during the period 1990
      to 2003. Symptoms and biochemical liver tests were compared before and after
      treatment. RESULTS: Sixteen patients underwent a total of 58 therapeutic
      endoscopic retrograde cholangiopancreatographies (ERCP). Sixteen endoscopic
      sphincterotomies, 15 balloon dilatations, 6 bougie dilatations, 3 stone/sludge
      extractions and 8 stentings were performed. Endoscopic therapy was technically
      successful in all patients (100%). Biochemical liver tests were significantly
      improved when compared with pretreatment values (p<0.001). Patients have been
      followed-up without stents except for the patients who had cholangiocarcinoma and
      cirrhosis at the beginning. Procedure-related early complications occurred in
      8.6% of therapeutic endoscopic biliary procedures. There was no mortality due to
      endoscopic treatment. Two patients whose stents were changed every two to three
      months had cholangitis due to stenting during 13 stent periods. Four patients
      whose stents were changed in seven to 10 days developed suppurative cholangitis
      (total 6 stent periods). CONCLUSIONS: Endoscopic therapy of symptomatic dominant
      strictures in primary sclerosing cholangitis is safe and effective. The
      cholangitis seen in long-term stenting seems to be solved by short-term stenting.

PMID- 15492912
TI  - The relation of Helicobacter pylori with intestinal metaplasia, gastric atrophy
      and BCL-2.
AB  - BACKGROUND/AIMS: It is assumed that the sequence of events in gastric cancer is
      as follows: chronic gastritis, atrophy, intestinal metaplasia (IM), dysplasia,
      and carcinoma. It is also known that Helicobacter pylori (Hp) can be involved in
      the chain of these chronic phenomena. Therefore, we studied the relation of Hp
      with chronic inflammation, atrophy, activity level, IM and bcl-2. METHODS: The
      number of patients included in this study was 52; 35 (67.3%) were female and 17
      (32.7%) were male. The average ages of women and men were determined as 44.5 and
      41.5 years, respectively. Hp was determined in 53.8% of all cases and chronic
      inflammation was found in all cases. No dysplasia or gastric cancer was found in
      our cases. A statistically significant positive correlation was found between the
      Hp intensity and the degrees of chronic inflammation, atrophy and activity.
      RESULTS: Bcl-2 was found positive in 7.1% of the patients with Hp, and in 4.1% of
      the Hp-negative patients. However, bcl-2 was positive in 2 (8.7%) of 23 Hp
      positive patients with chronic atrophic gastritis and in 1 (11.1%) of 9 Hp
      negative patients with chronic atrophic gastritis. In other words, bcl-2 was
      found more in Hp-negative chronic atrophic gastritis than in Hp-positive chronic
      atrophic gastritis. Also, atrophy and IM were present together in 2 bcl-2
      positive patients in whom Hp was positive. Bcl-2 was found positive more in IM
      than atrophy, proportionally. According to these data, although bcl-2 was found
      positive more often in Hp (+) cases proportionally, it was not statistically
      significant. Nevertheless, no significant difference was found between bcl-2
      positivity and atrophy according to the statistical data. The data regarding the
      relation between IM and bcl-2 were statistically significant, and a positive
      correlation was found between them. CONCLUSIONS: We concluded that Hp infections
      result in chronic gastritis, have a role in the development of atrophy and IM,
      and that Hp infection has a significant relation with neutrophile activation. The
      more Hp intensity increases, the greater the degrees of chronic gastritis,
      activity and atrophy. We also found that Hp, which is known to increase
      apoptosis, increases the expression of bcl-2, an anti-apoptotic gene, not
      directly but rather by causing atrophy development. We observed more bcl-2
      positivity in IM than in atrophy. Further studies with an extensive series of
      cases, including patients with dysplasia and gastric cancer, are needed to
      clarify statistical rates and to support the suggestion that bcl-2 expression
      increases with the progression to gastric cancer.

PMID- 15492913
TI  - Changes in the seroepidemiological pattern of Helicobacter pylori infection over
      the last 10 years.
AB  - BACKGROUND/AIMS: This study was undertaken to evaluate changes in the
      seroepidemiological pattern of Helicobacter pylori in a group of Turkish children
      over a span of 10 years. METHODS: A total of 403 (219+184) serum samples were
      obtained from a primary school located in the urban part of Ankara in 1990 and
      2000. All of the samples were from healthy students aged 7-14 (in 1990, n= 219,
      109 females; and in 2000, n= 184, 90 females). RESULTS: All serum samples were
      assayed for Helicobacter pylori IgG by means of enzyme-linked immunosorbent
      assay. The overall prevalence of Helicobacter pylori antibodies was 78.5% in 1990
      and 66.3% in 2000. The prevalence of Helicobacter pylori was found to be
      decreasing over a time span of 10 years (p<0.01). While the most susceptible age
      group to Helicobacter pylori in 1990 was 10 years (89.5%), in 2000 the
      susceptible age group was 8 years (85.0%). CONCLUSIONS: Our data suggest that the
      seroprevalence of Helicobacter pylori infection seems to have decreased during
      the last 10 years in Turkey. This change may be attributable to the changes in
      environmental condition and socioeconomic development that have taken place in
      the country.

PMID- 15492914
TI  - The effect of Helicobacter pylori eradication in patients with functional
      dyspepsia: assessment of different diagnostic tests.
AB  - BACKGROUND/AIMS: Helicobacter pylori infection, is seen in more than 80% of adult
      population in Turkey. The aims of this study were 1) to evaluate the importance
      of the diagnostic tests 2) to investigate the relationship between Hp infection
      and functional dyspepsia. METHODS: A total 75 patients with functional-dyspepsia
      were involved into the study. Hp infection was diagnosed by histopathological
      examination. CLO, cytology, culture, stool antigen and breath test. Symptom score
      using ROME II criteria was also evaluated to all patients. All patients were
      taken ranitidine-bismuth-citrate (400mg bid/day), clarithromycin (500 mg bid/day)
      and amoxicillin (1000 mg bid/day) for 14 days. All tests and symptom score
      analyses were re-applied at month 1 and 6. RESULTS: The eradication rate was
      95.9%. The baseline specifity of breath test, CLO, cytology, culture and stool
      antigen were 87.3%, 95.4%, 95.4% 94.5% and 86.4%, respectively. The sensitivity
      of such tests at first month after stopping the treatment were 86.1%, 100%, 100%,
      100%, 84.7%, respectively, and were 91.6%, 100%, 100%, 100%, 87.5%, respectively
      at six months after treatment. Symptom scores were 29.6+/-5.4, 15.8+/-4.7 and
      17.9+/-5.3 at baseline, first month and six months after treatment, respectively
      (p<0.001). CONCLUSIONS: The success of eradication may be related to use of
      bismuth which prevents antibiotic resistance development. Stool antigen and
      breath tests are less effective than invasive diagnostic-tests. The finding of
      improved symptomscores after eradication suggests that Hp may play a role in
      functional dyspepsia.

PMID- 15492915
TI  - Peutz-Jeghers syndrome: report of 6 cases in a family and management of polyps
      with intraoperative endoscopy.
AB  - BACKGROUND/AIMS: Peutz-Jeghers syndrome is an uncommon, autosomal dominantly
      inherited disorder characterized by mucocutaneous melanin pigmentation and
      gastrointestinal hamartomatous polyps. The purpose of this study was to present
      six cases of Peutz-Jeghers syndrome in a family. METHODS: Enteroclysis, upper and
      lower gastrointestinal endoscopy, and thyroid, abdominal, and testicular or
      breast ultrasonography were performed in all subjects. Tumor markers including
      CEA, alpha-FP, CA 19-9, CA 15-3, and CA 125 were measured. Management of polyps
      and complications were evaluated. RESULTS: History of the patients were as
      follows: patient 1 (40-year-old male) underwent surgery 20 years previously;
      patients 2 and 3 (19-year-old female and 17-year-old male) had undergone surgery
      three times between the ages of 11 and 18 years, and two times between the ages
      of 15 and 17 years, respectively; patient 4 (16-year-old male) had undergone
      surgery three times at the age of 13 years; patients 5 and 6 (14-year-old and 11
      year-old males) had no history of surgery. All surgical procedures had been
      performed due to intestinal obstruction. Hyperpigmentation of the lips and oral
      mucosa were observed in all patients except patient 1, whose pigmentation
      disappeared 20 years previously. Patient 2 also had pigmentation of hands and
      feet. Enteroclysis showed small bowel polyps in all subjects except patients 1
      and 6. During colonoscopy, different sizes of polyps were observed at different
      locations of the colon, and polyps larger than 1 cm were removed. Patients 2 and
      3 underwent surgery due to complication of small bowel polyps; 69 polyps in
      patient 2 and 17 polyps in patient 3 were removed via intraoperative endoscopic
      procedure. Hamartomatous lesions were confirmed by histopathological
      examinations. Microscopic study of polyps of patients 2 and 3 revealed dysplastic
      changes. None of the patients had evidence of malignancy as of June 2003. Peutz
      Jeghers syndrome demonstrated autosomal dominant inheritance in this family.
      CONCLUSIONS: The major problem during follow-up of patients with Peutz-Jeghers
      syndrome is the management of small bowel polyps. When encountered during
      surgery, intraoperative enteroscopic polypectomy should be performed.

PMID- 15492916
TI  - Spontaneous aortocaval fistula presenting with acute liver and renal failure: a
      case report.
AB  - Spontaneous aortocaval fistula is rare, occurring only in 3%-6% of all ruptured
      abdominal aortic aneurysms. A definitive diagnosis of aortocaval fistula is
      sometimes difficult, as the classic diagnostic signs (pulsatile abdominal mass
      with bruit, high-output heart failure and acute dyspnea) are present only in 20%
      50% of all such cases. Pre-operative diagnosis is crucial, as adequate
      preparation has to be made for the massive bleeding expected at operation.
      Surgical repair of aortocaval fistula is now standardized repair of the fistula.
      We report herein a case of spontaneous aortocaval fistula, which presented with
      liver and renal failure.

PMID- 15492917
TI  - Contrast-enhanced MR angiography of benign regenerative nodules following TIPS
      shunt procedure in Budd-Chiari syndrome.
AB  - In this report we describe the magnetic resonance (MR) angiographic features of
      benign hepatic nodules that developed in a patient with Budd-Chiari syndrome, and
      present the distinguishing features of benign regenerative nodules from
      hepatocellular cancer. In a 27-year-old woman with chronic Budd-Chiari syndrome,
      previously non-existing benign nodules developed in the liver parenchyma during
      the 10-month period following transjugular intrahepatic portosystemic (TIPS)
      shunt placement. The liver had been examined with gray-scale and Doppler
      sonography in addition to the MR imaging and MR angiography. On MR angiography,
      more hepatic nodules became visible in the portal venous phase compared to that
      of the arterial phase. Delayed washout of contrast medium in nodules was
      considered to be due to stasis in hepatic sinusoids. Hypervascularization,
      appearance after portosystemic shunt creation, multiplicity, small size ( <=2 cm
      in diameter in our patient), presence of peripheral rim, and high signal
      intensity on T1-weighted images are important imaging features of benign hepatic
      nodules that develop in patients with Budd-Chiari syndrome.

PMID- 15492918
TI  - Solid and cystic papillary neoplasms of the pancreas: report of four cases.
AB  - BACKGROUND/AIMS: In this report we present four cases with solid and cystic
      papillary neoplasms (SCPN) of the pancreas, and discuss the histopathological and
      immunohistochemical findings with a review of the literature. METHODS: The four
      cases reported here consisted of three women (ages 20-48, mean: 32) and one man
      (age: 58). The clinical diagnoses were confirmed with ultrasound (US) and
      computerized tomography (CT). The surgical management of the tumors included
      enucleation (1 patient), distal pancreatectomy with splenectomy (1) and distal
      pancreatectomy (2). RESULTS: The tumors were large (mean diameter of the resected
      tumor was 15 cm), had cystic degenerations between solid areas, and were
      distributed in the body and the tail of the pancreas. The cystic spaces contained
      hemorrhagic, necrotic and thrombotic material. The immunohistochemical studies
      revealed that the four tumors were all positive for a1 antitrypsin and neuron
      specific enolase, and were all negative for chromogranin. Vimentin and
      synaptophysin were positive in three different cases. The follow-up of the
      patients has been uneventful for 2, 1, 7 and 12 years, respectively. CONCLUSIONS:
      SCPN of the pancreas is an uncommon clinicopathologic entity with a relatively
      low grade malignant potential. The majority of the cases are young women. Fifty
      percent of the cases are asymptomatic, and the patients with symptoms generally
      suffer from an abdominal mass or abdominal pain. In spite of the characteristic
      macroscopic and microscopic aspects, the immunophenotypical view is nonspecific.
      Prognosis is excellent after complete surgical resection and recurrence is rarely
      seen. Metastatic spread is not expected and the tumor usually has a manner of
      local invasion. Acinar cell carcinoma, pancreatoblastoma and pancreatic endocrine
      tumor must be considered in the differential diagnosis.

PMID- 15492919
TI  - Serous microcystic adenoma of the pancreas: case report and review of the
      literature.
AB  - Cystic tumors of the pancreas are rare neoplasms. They are more frequently
      identified given the improvements in imaging techniques. Serous cystadenomas are
      the most common among cystic neoplasms of the pancreas. In this case report we
      present a patient who was incidentally found to have a cystic mass in the
      pancreas during an abdominal imaging done for unrelated reasons and was diagnosed
      as serous cystadenoma of the pancreas. She was asymptomatic on admission and was
      operated six years later because of the progressive growth of the tumor during
      that period. Distal pancreatectomy was performed. Histopathologic examination of
      the surgery specimen confirmed the diagnosis of serous microcystic adenoma.
      Despite their rarity, serous cystadenomas should be kept in mind in the
      differential diagnosis of the cystic lesions of the pancreas. Furthermore, the
      differentiation of serous cystadenoma from other cystic tumors as well as from
      non-neoplastic cysts is very important because of the great difference in their
      management.

PMID- 15492920
TI  - Synchronous primary adenocarcinoma and gastrointestinal stromal tumor in the
      stomach: a report of two cases.
AB  - Synchronous occurrence of epithelial and gastrointestinal stromal tumors (GISTs)
      in the stomach is uncommon. This association has often been detected incidentally
      on gastric mucosa or serosa, or occasionally intramurally, at surgery or
      gastroscopy for other reasons. Various hypotheses have been proposed regarding
      this simultaneous development, and it is not known whether or not such an
      association is a simple incidental coexistence or whether the two lesions are
      connected by a causal relationship. In this article, we report two cases of
      synchronous development of stromal tumor and adenocarcinoma incidentally detected
      in the stomach in two elderly patients.

PMID- 15492921
TI  - Celiac disease in patients having recurrent aphthous stomatitis.
AB  - BACKGROUND/AIMS: Celiac disease is a condition related to the small intestine's
      intolerance to gluten. In epidemiologic studies the prevalence is highly
      variable. The diagnosis can be difficult due to the wide spectrum of signs and
      symptoms. As the risk for intestinal lymphoma is higher in these patients, early
      diagnosis has its privileges. The higher prevalence of recurrent aphthous
      stomatitis in celiac disease led us to investigate the celiac disease prevalence
      in patients with recurrent aphthous stomatitis, which might assist in diagnosis
      of asymptomatic celiac disease patients. The aim of this study was to determine
      the prevalence of celiac disease in patients presenting with recurrent aphthous
      stomatitis. METHODS: The study group consisted of patients having a history of
      recurrent aphthous stomatitis. The control group included patients not having
      aphthous stomatitis. Antibodies to gliadin IgG and IgA and antibodies to
      endomysium were determined from the serum samples of all patients. Biopsies were
      obtained from the distal part of the duodenum. RESULTS: Biopsies of two patients
      (4.8%) out of 41 belonging to the study group were diagnosed as celiac disease.
      In serum samples of both, antibodies to gliadin IgA and antibodies to endomysium
      were found to be positive. Antibodies to gliadin IgG antibody were positive in
      only one of these two patients. None of the 49 patients in the control group was
      diagnosed as celiac disease. CONCLUSION: Further evaluation of recurrent aphthous
      stomatitis patients for celiac disease must be performed. As the endoscopic
      procedures are invasive and costly, evaluation of recurrent aphthous stomatitis
      patients for celiac disease must include serologic markers at the beginning. If
      any positivity is determined in markers, then endoscopic procedures including
      biopsies of the duodenum must be considered as the second-step intervention.

PMID- 15492922
TI  - Crohn's disease with isolated esophagus and gastric involvement.
AB  - Isolated esophagus and stomach involvement in Crohn's disease is rather rare. We
      present here a female patient aged 35 years, who presented with complaints of
      fatigue, difficulty in swallowing, nausea, and vomiting, and who was diagnosed as
      esophago-gastric Crohn's disease.

PMID- 15492923
TI  - Extensive adult colo-colonic intussusception from ascending colon to sigmoid
      colon: report of a case.
AB  - Intussusception in adults is relatively rare. Here we report a 52-year-old man
      with an extensive colo-colonic intussusception caused by a polypoid mass in the
      ascending colon. The mass, which was 10 x 8 x 5 cm in size, had been palpated
      preoperatively and was suspected to be a sigmoid tumor. The patient was treated
      successfully by reduction of the invagination and subsequent right hemicolectomy.

PMID- 15492924
TI  - Letter to the editor: A case report of primary retroperitoneal hydatid cyst.

PMID- 15492925
TI  - Mutations of CDKL5 cause a severe neurodevelopmental disorder with infantile
      spasms and mental retardation.
AB  - Rett syndrome (RTT) is a severe neurodevelopmental disorder caused, in most
      classic cases, by mutations in the X-linked methyl-CpG-binding protein 2 gene
      (MECP2). A large degree of phenotypic variation has been observed in patients
      with RTT, both those with and without MECP2 mutations. We describe a family
      consisting of a proband with a phenotype that showed considerable overlap with
      that of RTT, her identical twin sister with autistic disorder and mild-to
      moderate intellectual disability, and a brother with profound intellectual
      disability and seizures. No pathogenic MECP2 mutations were found in this family,
      and the Xq28 region that contains the MECP2 gene was not shared by the affected
      siblings. Three other candidate regions were identified by microsatellite
      mapping, including 10.3 Mb at Xp22.31-pter between Xpter and DXS1135, 19.7 Mb at
      Xp22.12-p22.11 between DXS1135 and DXS1214, and 16.4 Mb at Xq21.33 between
      DXS1196 and DXS1191. The ARX and CDKL5 genes, both of which are located within
      the Xp22 region, were sequenced in the affected family members, and a deletion of
      nucleotide 183 of the coding sequence (c.183delT) was identified in CDKL5 in the
      affected family members. In a screen of 44 RTT cases, a single splice-site
      mutation, IVS13-1G-->A, was identified in a girl with a severe phenotype
      overlapping RTT. In the mouse brain, Cdkl5 expression overlaps--but is not
      identical to--that of Mecp2, and its expression is unaffected by the loss of
      Mecp2. These findings confirm CDKL5 as another locus associated with epilepsy and
      X-linked mental retardation. These results also suggest that mutations in CDKL5
      can lead to a clinical phenotype that overlaps RTT. However, it remains to be
      determined whether CDKL5 mutations are more prevalent in specific clinical
      subgroups of RTT or in other clinical presentations.

PMID- 15492926
TI  - CYP3A variation and the evolution of salt-sensitivity variants.
AB  - Members of the cytochrome P450 3A subfamily catalyze the metabolism of endogenous
      substrates, environmental carcinogens, and clinically important exogenous
      compounds, such as prescription drugs and therapeutic agents. In particular, the
      CYP3A4 and CYP3A5 genes play an especially important role in pharmacogenetics,
      since they metabolize >50% of the drugs on the market. However, known genetic
      variants at these two loci are not sufficient to account for the observed
      phenotypic variability in drug response. We used a comparative genomics approach
      to identify conserved coding and noncoding regions at these genes and resequenced
      them in three ethnically diverse human populations. We show that remarkable
      interpopulation differences exist with regard to frequency spectrum and haplotype
      structure. The non-African samples are characterized by a marked excess of rare
      variants and the presence of a homogeneous group of long-range haplotypes at high
      frequency. The CYP3A5*1/*3 polymorphism, which is likely to influence salt and
      water retention and risk for salt-sensitive hypertension, was genotyped in >1,000
      individuals from 52 worldwide population samples. The results reveal an unusual
      geographic pattern whereby the CYP3A5*3 frequency shows extreme variation across
      human populations and is significantly correlated with distance from the equator.
      Furthermore, we show that an unlinked variant, AGT M235T, previously implicated
      in hypertension and pre-eclampsia, exhibits a similar geographic distribution and
      is significantly correlated in frequency with CYP3A5*1/*3. Taken together, these
      results suggest that variants that influence salt homeostasis were the targets of
      a shared selective pressure that resulted from an environmental variable
      correlated with latitude.

PMID- 15492927
TI  - Ignoring linkage disequilibrium among tightly linked markers induces false
      positive evidence of linkage for affected sib pair analysis.
AB  - Most multipoint linkage programs assume linkage equilibrium among the markers
      being studied. The assumption is appropriate for the study of sparsely spaced
      markers with intermarker distances exceeding a few centimorgans, because linkage
      equilibrium is expected over these intervals for almost all populations. However,
      with recent advancements in high-throughput genotyping technology, much denser
      markers are available, and linkage disequilibrium (LD) may exist among the
      markers. Applying linkage analyses that assume linkage equilibrium to dense
      markers may lead to bias. Here, we demonstrated that, when some or all of the
      parental genotypes are missing, assuming linkage equilibrium among tightly linked
      markers where strong LD exists can cause apparent oversharing of multipoint
      identity by descent (IBD) between sib pairs and false-positive evidence for
      multipoint model-free linkage analysis of affected sib pair data. LD can also
      mimic linkage between a disease locus and multiple tightly linked markers, thus
      causing false-positive evidence of linkage using parametric models, particularly
      when heterogeneity LOD score approaches are applied. Bias can be eliminated by
      inclusion of parental genotype data and can be reduced when additional unaffected
      siblings are included in the analysis.

PMID- 15492929
TI  - Open access. A turning point in scientific publication.

PMID- 15492928
TI  - CHEK2 is a multiorgan cancer susceptibility gene.
AB  - A single founder allele of the CHEK2 gene has been associated with predisposition
      to breast and prostate cancer in North America and Europe. The CHEK2 protein
      participates in the DNA damage response in many cell types and is therefore a
      good candidate for a multisite cancer susceptibility gene. Three founder alleles
      are present in Poland. Two of these result in a truncated CHEK2 protein, and the
      other is a missense substitution of an isoleucine for a threonine. We ascertained
      the prevalence of each of these alleles in 4,008 cancer cases and 4,000 controls,
      all from Poland. The majority of the common cancer sites were represented.
      Positive associations with protein-truncating alleles were seen for cancers of
      the thyroid (odds ratio [OR] 4.9; P=.0006), breast (OR 2.2; P=.02), and prostate
      (OR 2.2; P=.04). The missense variant I157T was associated with an increased risk
      of breast cancer (OR 1.4; P=.02), colon cancer (OR 2.0; P=.001), kidney cancer
      (OR 2.1; P=.0006), prostate cancer (OR 1.7; P=.002), and thyroid cancer (OR 1.9;
      P=.04). The range of cancers associated with mutations of the CHEK2 gene may be
      much greater than previously thought.

PMID- 15492930
TI  - Streptococcus pneumoniae and its bacteriophages: one long argument.
AB  - Infectious diseases currently kill more than 15 million people annually, and the
      WHO estimates that every year 1.6 million people die from pneumococcal diseases.
      Streptococcus pneumoniae (pneumococcus), a bacterium with a long biological
      pedigree, best illustrates the rapid evolution of antibiotic resistance, which
      has led to major public health concern. This article discusses the molecular
      basis of the two main virulence factors of pneumococcus, the capsule and cell
      wall hydrolases, as well as new approaches to developing medicinal weapons for
      preventing pneumococcal infections. In addition, current knowledge regarding
      pneumococcal phages as potential contributors to virulence and the use of lytic
      enzymes encoded by these phages as therapeutic tools is reviewed.

PMID- 15492931
TI  - Bacterial degradation of aromatic pollutants: a paradigm of metabolic
      versatility.
AB  - Although most organisms have detoxification abilities (i.e mineralization,
      transformation and/or immobilization of pollutants), microorganisms, particularly
      bacteria, play a crucial role in biogeochemical cycles and in sustainable
      development of the biosphere. Next to glucosyl residues, the benzene ring is the
      most widely distributed unit of chemical structure in nature, and many of the
      aromatic compounds are major environmental pollutants. Bacteria have developed
      strategies for obtaining energy from virtually every compound under oxic or
      anoxic conditions (using alternative final electron acceptors such as nitrate,
      sulfate, and ferric ions). Clusters of genes coding for the catabolism of
      aromatic compounds are usually found in mobile genetic elements, such as
      transposons and plasmids, which facilitate their horizontal gene transfer and,
      therefore, the rapid adaptation of microorganisms to new pollutants. A successful
      strategy for in situ bioremediation has been the combination, in a single
      bacterial strain or in a syntrophic bacterial consortium, of different degrading
      abilities with genetic traits that provide selective advantages in a given
      environment. The advent of high-throughput methods for DNA sequencing and
      analysis of gene expression (genomics) and function (proteomics), as well as
      advances in modelling microbial metabolism in silico, provide a global, rational
      approach to unravel the largely unexplored potentials of microorganisms in
      biotechnological processes thereby facilitating sustainable development.

PMID- 15492932
TI  - Hijacking of eukaryotic functions by intracellular bacterial pathogens.
AB  - Intracellular bacterial pathogens have evolved as a group of microorganisms
      endowed with weapons to hijack many biological processes of eukaryotic cells.
      This review discusses how these pathogens perturb diverse host cell functions,
      such as cytoskeleton dynamics and organelle vesicular trafficking. Alteration of
      the cytoskeleton is discussed in the context of the bacterial entry process
      (invasion), which occurs either by activation of membrane-located host receptors
      ("zipper" mechanism) or by injection of bacterial proteins into the host cell
      cytosol ("trigger" mechanism). In addition, the two major types of intracellular
      lifestyles, cytosolic versus intravacuolar (phagosomal), which are the
      consequence of alterations in the phagosome-lysosome maturation route, are
      compared. Specific examples illustrating known mechanisms of mimicry or hijacking
      of the host target are provided. Finally, recent advances in phagosome proteomics
      and genome expression in intracellular bacteria are described. These new
      technologies are yielding valuable clues as to how these specialized bacterial
      pathogens manipulate the mammalian host cell.

PMID- 15492933
TI  - Fe-Si biominerals in the Vilyuchinskie hot springs, Kamchatka Peninsula, Russia.
AB  - The micromorphological structure of microbial mats (biomats) from the hot springs
      of the Vilyuchinskaya hydrothermal system, Kamchatka Peninsula, Russia, were
      investigated. The Vilyuchinskie hot springs had a discharge temperature of 55-56
      degrees C and Na-Ca-HCO3-type waters rich in silicic and boric acids. Water and
      biomats had high concentrations of Fe, Mn, Sr, and As. Enumeration of total
      bacterial abundance (TBA) demonstrated a low density of bacterial populations.
      However, the fractions of metabolically active bacteria and respiring iron
      oxidizing bacteria in the hot-spring water were high, comprising 68 and 21% of
      TBA, respectively. Scanning electron microscopy equipped with an energy
      dispersive X-ray spectrometer (SEM-EDX) showed that unicellular rod-shaped
      bacteria about 5-microm long predominated in the brown biomats. The mineral
      capsules of these bacteria contained large amounts of Fe and Si. Extracellular
      and intracellular particles were observed by transmission electron microscopy. Fe
      oxidizing bacteria were isolated from the biomats on agar plates with selective
      medium. Therefore, it can be concluded that microorganisms inhabiting the biomats
      of the Vilyuchinskie hot springs are essential for the deposition of Fe-minerals
      at neutral pH.

PMID- 15492934
TI  - A new set of DNA macrochips for the yeast Saccharomyces cerevisiae: features and
      uses.
AB  - The yeast Saccharomyces cerevisiae has been widely used for the implementation of
      DNA chip technologies. For this reason and due to the extensive use of this
      organism for basic and applied studies, yeast DNA chips are being used by many
      laboratories for expression or genomic analyses. While membrane arrays
      (macroarrays) offer several advantages, for many laboratories they are not
      affordable. Here we report that a cluster of four Spanish molecular-biology yeast
      laboratories, with relatively small budgets, have developed a complete set of
      probes for the genome of S. cerevisiae. These have been used to produce a new
      type of macroarray on a nylon surface. The macroarrays have been evaluated and
      protocols for their use have been optimized.

PMID- 15492935
TI  - Resistance to beta-lactam antibiotics in Aeromonas hydrophila isolated from
      rainbow trout (Oncorhynchus mykiss).
AB  - Bacterial infections caused by members of the genus Aeromonas, with a relatively
      high antibiotic resistance, are among the most common and troublesome diseases of
      fish raised in ponds with recirculation systems. In this study, carried out at an
      experimental aquaculture station in northern Portugal, 51 strains identified as
      belonging to the genus Aeromonas were isolated from 20 rainbow trout
      (Oncorhynchus mykiss) skin and kidney samples, as well as from raceway water
      samples. Macro- and microscopic examination of the fish tissues revealed lesions
      or cellular alterations in skin and kidney that seemed to correlate with the
      presence of those isolates. The sensitivity of all isolated strains to different
      groups of beta-lactam antibiotics (penicillins, cephalosporins, monobactams and
      carbapenems) was evaluated using the disc diffusion method. The highest rates of
      resistance were to amoxicillin, carbenicillin and ticarcillin. Unexpected
      resistance to imipenem, an antibiotic of clinical usage, was also detected, which
      suggests that resistance may have been transferred to the Aeromonas population
      from the environment.

PMID- 15492936
TI  - Fecal pollution in water from storm sewers and adjacent seashores in Natal, Rio
      Grande do Norte, Brazil.
AB  - A study on the distribution patterns of enteropathogenic bacteria polluting the
      shoreline in Natal, Rio Grande do Norte, Brazil, was carried out based on 72
      samples obtained from three storm sewers and adjoining beach locations, Praia do
      Meio (PM), Areia Preta (AP) and Ponta Negra (PN). From each location, 12 water
      samples were taken and analyzed for fecal coliforms (FC) and Escherichia coli. In
      AP, two (16.7%) of the seawater samples and five (41.7%) of the storm sewer
      samples yielded values above 1.1 x 107 FC/100 ml, whereas only one (8.3%) of the
      samples from PM reached this level. There was no correlation (p > 0.05) between
      rainfall indices and FC values. A total of 64 E. coli isolates were obtained: 37
      from the storm sewer samples and 27 from the seawater samples. Of these isolates,
      four (O143, two O112ac, and O124) were enteroinvasive and two (O111 and O125)
      were enteropathogenic. Resistance to antibiotics and to heavy metals was also
      analyzed. Almost 36% of the E. coli strains isolated were resistant to more than
      one antibiotic. All strains were resistant to zinc and copper at the highest
      concentration tested (250 microg/ml), and several (23.4%) were resistant to
      mercury at 50 microg/ml. Our results agreed with previous reports that antibiotic
      resistance is commonly associated with heavy-metal resistance in pathogens.

PMID- 15492937
TI  - Functional characteristics of culturable bacterioplankton from marine and
      estuarine environments.
AB  - Information on the structure of bacterioplankton communities is continuously
      increasing, while knowledge of their metabolic capabilities remains limited. In
      this study, the metabolic capacity of bacterioplankton was investigated, as such
      information is necessary to fully understand carbon cycling and other
      biogeochemical processes. The diversity of dominant culturable chemoorganotrophic
      bacteria from one estuarine and three marine environments was analyzed by random
      isolation of colony-forming units on solid media, taxonomical identification by
      partial 16S rRNA gene sequence analysis, and functional characterization of the
      isolates. A total of 76 16S rRNA gene sequences, representing 19 different
      genotypes, were obtained from the four sampling localities, including Bacillus,
      Pseudomonas, Pseudoalteromonas, Vibrio, and Erythrobacter as the most frequently
      isolated genera. The range of metabolic functions possessed by the cultured
      bacterial assemblages differed significantly between sites. Similarly, the
      percentage at each sampling station of bacteria capable of performing a specific
      function was significantly different for 18 of the 25 investigated metabolic
      functions. At two localities, the bacterial assemblages were dominated by a
      single genus (Pseudoalteromonas or Erythrobacter) and appeared to be functionally
      specialized. More than 95% of the isolates were capable of utilizing dissolved
      free amino acids and protein as their sole nitrogen sources, and all isolates of
      the specialized assemblages expressed beta-glucosidase. Furthermore, only some of
      the isolates were able to utilize NH4+, while up to two thirds of the isolates of
      the two marine sites were able to grow on NO3-.

PMID- 15492939
TI  - Quiz page. Tuberous sclerosis complex.

PMID- 15492941
TI  - Acute interstitial nephritis associated with atazanavir, a new protease
      inhibitor.
AB  - Atazanavir is a new human immunodeficiency virus 1 protease inhibitor that has a
      favorable side-effect profile and is available in once-daily dosing. We report
      the case of a young man with human immunodeficiency virus infection who developed
      acute renal failure after therapy with this drug. Renal biopsy showed acute
      interstitial nephritis. This is the first report of acute interstitial nephritis
      from atazanavir.

PMID- 15492942
TI  - A novel alpha-galactosidase a mutant (M42L) identified in a renal variant of
      Fabry disease.
AB  - A 65-year-old man presented to our institution for workup of proteinuria. His
      serum creatinine level was 1.7 mg/dL (130 micromol/L), and he had proteinuria
      with protein of almost 5 g/24 h. Fabry disease was diagnosed by means of kidney
      biopsy and low serum and leukocyte levels of alpha-galactosidase A. Review of his
      history, family history, physical examinations, and diagnostic studies did not
      show other findings typical of this disease. His renal function continued to
      decline, and he eventually underwent a living unrelated renal transplantation 5
      years later. Three years after transplantation, his creatinine level is 1.7 mg/dL
      (130 micromol/L), and corrected iothalamate clearance is 53 mL/min/1.73 m2 .
      Genetic studies showed that he has a novel missense mutation (M42L) in exon 1.
      Methionine at codon 42 is highly conserved in eukaryotic alpha-galactosidase A
      orthologues. This genotype predicts a minor misfolding of alpha-galactosidase A
      because of a small difference in hydrophobicity between methionine and leucine.
      His mutation resulted in a very low, but detectable, serum level of alpha
      galactosidase A (0.002 U/L; normal range, 0.016 to 0.2 U/L). Cases of Fabry
      disease that present with predominantly renal manifestations are rare and require
      a high index of suspicion for diagnosis. Because treatment for Fabry disease
      recently has become available, it is important for clinicians to be aware of this
      disease and pursue the diagnosis in cases of otherwise unexplained renal
      dysfunction.

PMID- 15492943
TI  - Dialysis catheter-related bacteremia: treatment and prophylaxis.
AB  - Catheter-related bacteremia is a major cause of morbidity among hemodialysis
      patients. This article reviews the medical literature regarding the treatment and
      prophylaxis of catheter-related bacteremia. Bacterial biofilm that forms in the
      catheter lumen is the source of catheter-related bacteremia. Treatment with
      systemic antibiotics alone fails to definitively eradicate the infection in most
      patients. Catheter-related bacteremia can be managed by either catheter removal
      with delayed placement of a new catheter or exchange of the infected catheter
      with a new catheter over a guidewire. More recent studies suggested that
      instillation of an antibiotic-anticoagulant lock into the catheter lumen, as an
      adjunct to systemic antibiotic therapy, can cure approximately two thirds of
      catheter-related bacteremias without requiring catheter replacement. The
      frequency of catheter-related bacteremia may be reduced by using tunneled, rather
      than nontunneled, dialysis catheters and strict aseptic technique. In addition,
      several pharmacological measures may be useful for prophylaxis against catheter
      related bacteremia. These include application of an antimicrobial ointment
      (mupirocin or polysporin [Pfizer, New York, NY]) to the catheter exit site or
      instillation of an antimicrobial solution (gentamicin or taurolidine) into the
      catheter lumen. Subcutaneous dialysis devices do not reduce the frequency of
      catheter-related bacteremia unless an antimicrobial solution is instilled into
      the device. The development and widespread adoption of effective approaches to
      the treatment and prophylaxis of catheter-related bacteremia will dramatically
      reduce the morbidity and economic burden associated with this complication.

PMID- 15492945
TI  - ESRD caused by nephrolithiasis: prevalence, mechanisms, and prevention.
AB  - BACKGROUND: The contribution of nephrolithiasis-related end-stage renal disease
      (ESRD) to patients requiring renal replacement therapy has never been
      specifically evaluated. METHODS: Of the entire cohort of 1,391 consecutive
      patients who started maintenance dialysis therapy at our nephrology department
      between January 1989 and December 2000, a total of 45 patients (21 men) had renal
      stone disease as the cause of ESRD and constitute the study material. Type and
      cause of renal stone disease was determined in the 45 patients, as well as the
      change in prevalence of nephrolithiasis-related ESRD with time during this 12
      year period. RESULTS: The overall proportion of nephrolithiasis-related ESRD was
      3.2%. Infection (struvite) stones accounted for 42.2%; calcium stones, 26.7%;
      uric acid nephrolithiasis, 17.8%; and hereditary diseases (including primary
      hyperoxaluria type 1 and cystinuria), 13.3% of cases. Women were predominant
      among patients with infection and calcium stones, whereas men were predominant
      among patients with uric acid or hereditary stone disease. The proportion of
      patients with nephrolithiasis-related ESRD decreased from 4.7% in the triennial
      period 1989 to 1991 to 2.2% in the most recent period, 1998 to 2000 ( P = 0.07).
      This tendency to a decreasing prevalence mainly was caused by a rarefaction of
      infection and calcium stones with time, whereas frequencies of uric acid and
      hereditary stone disease remained essentially unchanged. CONCLUSION: Severe forms
      of nephrolithiasis remain an underestimated cause of potentially avoidable ESRD
      and need for renal replacement therapy. These findings highlight the crucial
      importance of accurate stone analysis and metabolic evaluation to provide early
      diagnosis and proper therapy for conditions that may lead to ESRD through
      recurrent stone formation and/or parenchymal crystal infiltration.

PMID- 15492944
TI  - Albuminuria is evident in the early stages of diabetes onset: results from the
      Australian Diabetes, Obesity, and Lifestyle Study (AusDiab).
AB  - BACKGROUND: Albuminuria is a common complication of diabetes and a leading cause
      of end-stage renal disease. We determined the prevalence of and factors
      associated with albuminuria in an Australian population and examined the
      association of albuminuria with glucose tolerance. METHODS: The Australian
      Diabetes, Obesity, and Lifestyle Study included 11,247 adults aged 25 years and
      older from 42 randomly selected areas of Australia. Microalbuminuria is defined
      as an albumin-creatinine ratio of 22 to 220 mg/g (2.5 to 25 mg/mmol) in men and
      31 to 220 mg/g (3.5 to 25 mg/mmol) in women, and macroalbuminuria is defined as
      an albumin-creatinine ratio of 220 mg/g or greater (> or =25.0 mg/mmol). RESULTS:
      Overall, 25.3% of patients with diabetes mellitus (known [KDM] and newly
      diagnosed [NDM], type 1 and type 2) had evidence of albuminuria (21.0%,
      microalbuminuria; 4.3%, macroalbuminuria). Prevalence increased with increasing
      glycemia (normal glucose tolerance [NGT], 5.1%; impaired fasting glucose [IFG],
      9.3%; impaired glucose tolerance, 11.0%; NDM, 17.8%; and KDM, 32.6% [type 2
      only]). Patients with diabetes (KDM and NDM) and IFG had an increased risk for
      albuminuria compared with those with NGT independent of age, sex, and other known
      risk factors for albuminuria. Logistic regression modeling identified age,
      duration of diabetes, systolic blood pressure, current smoking, body mass index,
      and glycated hemoglobin level as independent risk factors for albuminuria.
      CONCLUSION: This Australian population-based study shows that albuminuria is
      common among patients with established diabetes, is present before the onset of
      diabetes, and becomes more prevalent with worsening glucose tolerance.

PMID- 15492946
TI  - Relationship between predicted creatinine clearance and proteinuria and the risk
      of developing ESRD in Okinawa, Japan.
AB  - BACKGROUND: Chronic kidney disease and a low creatinine clearance (CrCl) are
      relatively common, particularly in the aged population. However, the renal
      outcome of a low CrCl is not known. METHODS: Participants in a 1993 mass
      screening conducted by the Okinawa General Health Maintenance Association in
      Okinawa, Japan, were investigated. A total of 95,255 subjects (40,157 men, 55,098
      women) older than 20 years for whom serum creatinine (SCr) data were available
      were studied. CrCl was calculated as a surrogate marker of glomerular filtration
      rate by using the Cockcroft-Gault method. All dialysis patients who were treated
      in Okinawa were independently registered in the Okinawa Dialysis Study registry.
      Participants in the 1993 screening who later entered a dialysis program were
      identified by using the 2 computer registries. The cumulative incidence of end
      stage renal disease (ESRD) was calculated according to baseline CrCl level in
      quartiles. The significance of CrCl for the risk for developing ESRD was
      evaluated by means of Cox analysis after adjusting for age, sex, blood pressure,
      and proteinuria. RESULTS: CrCl values were distributed into quartiles: CrCl I,
      less than 50.2 mL/min (<0.84 mL/s; n = 23,076); CrCl II, 50.2 to 63.9 mL/min
      (0.84 to 1.07 mL/s; n = 23,039); CrCl III, 64.0 to 79.3 mL/min (1.07 to 1.32
      mL/s; n = 23,147); and CrCl IV, 79.4 mL/min or greater (> or =1.32 mL/s; n =
      23,036). One hundred eighty-one subjects with data for SCr level were identified
      in the dialysis registry. Seven-year cumulative incidences of ESRD per 1,000
      subjects were 86.8 in CrCl I, 13.6 in CrCl II, 8.3 in CrCl III, and 7.9 in CrCl
      IV in patients who had proteinuria, whereas they were 1.2, 0.7, 0.04, and 0.13 in
      those who did not have proteinuria, respectively. As CrCl category decreased, the
      adjusted hazard ratio for the risk of developing ESRD was 4.353 (95% confidence
      interval, 3.412 to 5.553; P < 0.0001). CONCLUSION: The prevalence of a low CrCl
      (CrCl I, <50.2 mL/min [<0.84 mL/s]) was relatively high in the elderly
      population. Subjects with a low CrCl who had proteinuria were at high risk of
      developing ESRD. However, the cumulative incidence of ESRD was not as high in
      patients with a low CrCl not associated with proteinuria. Screening by means of
      dipstick for proteinuria is useful, particularly among the elderly, to identify
      subjects in a high-risk population.

PMID- 15492947
TI  - Twenty-one-year trend in ESRD due to focal segmental glomerulosclerosis in the
      United States.
AB  - BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a clinicopathologic
      syndrome with a substantial risk for progression to end-stage renal disease
      (ESRD). Recent studies of renal biopsy archives in the United States suggest that
      the incidence of FSGS has increased. FSGS has become the leading cause of
      idiopathic nephrotic syndrome in the United States, with the greatest incidence
      rates in the black population. In the absence of a population-based estimate of
      FSGS incidence, we wished to obtain a population-based estimate of incident ESRD
      cases caused by FSGS (FSGS ESRD) and characterize temporal changes in this group.
      METHODS: We examined the incidence of FSGS ESRD during a 21-year period (1980 to
      2000) using data from the United States Renal Data System. We excluded patients
      who were classified as having acquired immunodeficiency syndrome nephropathy.
      RESULTS: The annual incidence of FSGS ESRD has increased considerably, whether
      expressed as an absolute number or a fraction of the total incident ESRD
      population. Thus, the proportion of ESRD attributed to FSGS has increased 11
      fold, from 0.2% in 1980 to 2.3% in 2000. The recent increase in incident FSGS
      ESRD cases likely is multifactorial in origin, with contributions from changes in
      renal biopsy practices, changes in disease classification, and a real increase in
      the incidence of FSGS disease. Black individuals have a 4-fold greater risk of
      FSGS ESRD than white or Asian individuals. The peak decade for FSGS ESRD
      incidence is 40 to 49 years among black subjects and 70 to 79 years among white
      and Asian individuals. Males have 1.5- to 2-fold greater risk than females.
      CONCLUSION: The incidence of FSGS ESRD has increased considerably in the United
      States, with black individuals at greatest risk. Idiopathic FSGS now is the most
      common cause of ESRD caused by primary glomerular disease in the United States in
      both the black and white populations.

PMID- 15492948
TI  - Increased expression of urotensin II and urotensin II receptor in human diabetic
      nephropathy.
AB  - BACKGROUND: Urotensin II (UII) is an 11-amino acid vasoactive peptide, recently
      identified as the ligand for a novel G protein-coupled receptor, GPR-14 (renamed
      urotensin receptor [UT]). In addition to its potent vasoconstrictive actions, UII
      also has trophic and profibrotic effects, leading to its implication in the
      pathogenesis of heart failure. However, elevated plasma UII levels also were
      reported in association with renal impairment and diabetes. Accordingly, the
      present study sought to examine the expression and localization of UII and its
      receptor in kidney tissue from patients with diabetic nephropathy. METHODS: We
      quantified UII and UT gene expression in renal biopsy tissue samples from
      patients with diabetic nephropathy by using quantitative real-time polymerase
      chain reaction and determined the intrarenal distribution of their peptides by
      means of immunohistochemistry. RESULTS: In human diabetic tissue, gene expression
      of UII and UT were increased 45- and almost 2,000-fold in comparison to control
      nephrectomy tissue, respectively (P < 0.0001). Immunohistochemical studies showed
      intense UII peptide staining in diabetic tissue localized predominantly to
      tubular epithelial cells, and fluorescein-labeled ligand binding studies showed a
      similar tubular pattern of distribution. CONCLUSION: In the context of its known
      biological actions, the dramatic overexpression of UII and its receptor implicate
      this vasoactive peptide as a possible novel factor in the pathogenesis of
      diabetic nephropathy.

PMID- 15492949
TI  - Effect of gemfibrozil on change in renal function in men with moderate chronic
      renal insufficiency and coronary disease.
AB  - BACKGROUND: Limited data suggest that low levels of serum high-density
      lipoprotein cholesterol (HDL-C) and high levels of triglyceride-rich lipoproteins
      may be associated with more rapid rates of kidney function loss in individuals
      with chronic renal insufficiency (CRI). Although fibric acid derivatives increase
      serum HDL-C levels and decrease triglyceride levels, their effects on renal
      function are largely unknown. We conducted this study to determine whether
      gemfibrozil reduced rates of renal function loss in people with moderate CRI.
      METHODS: This was a post hoc subgroup analysis in the Veterans Affairs High
      Density Lipoprotein Intervention Trial, a randomized double-blind trial of
      gemfibrozil versus placebo in 2,531 men with coronary disease, HDL-C levels of 40
      mg/dL or less (< or =1.0 mmol/L), low-density lipoprotein cholesterol levels of
      140 mg/dL or less (< or =3.6 mmol/L), and a range of triglyceride values.
      Moderate CRI is defined as estimated glomerular filtration rate (GFR) of 30 to
      59.9 mL/min/1.73 m2 at baseline. Multivariate regression was used to calculate
      rates of decline in estimated GFR for individuals administered gemfibrozil or
      placebo, controlling for prospectively determined potential confounders. RESULTS:
      Change in renal function could be calculated in 1,981 individuals, of whom 399
      individuals (20.2%) were eligible for inclusion. Among 399 study subjects, the
      rate of change in renal function in the gemfibrozil group during a median of 61
      months was not significantly different from that in the placebo group (0.49
      mL/min/1.73 m2/y faster; 95% confidence interval, 0.09 slower to 1.09 faster; P =
      0.10). No clinically relevant effect of gemfibrozil on renal function was
      observed in groups defined by baseline lipid levels, kidney function, diabetic
      status, or other components of the metabolic syndrome. The incidence of transient
      (10% versus 4%; P = 0.01), but not sustained (9% versus 4%; P = 0.07), increases
      in serum creatinine levels of 0.5 mg/dL or greater (> or =44 micromol/L) was
      significantly greater in the gemfibrozil group. However, in 5 subjects with acute
      increases in serum creatinine levels, serum creatine kinase levels were
      significantly elevated as well, suggesting that myocyte toxicity may have been
      responsible. Even when these individuals were excluded, no clinically significant
      effect of gemfibrozil on kidney function was observed. CONCLUSION: Gemfibrozil
      does not appear to exert a clinically relevant effect on rates of kidney function
      loss in individuals with moderate CRI, low HDL-C levels, and concomitant coronary
      disease.

PMID- 15492950
TI  - Increased total number but impaired migratory activity and adhesion of
      endothelial progenitor cells in patients on long-term hemodialysis.
AB  - BACKGROUND: Endothelial progenitor cells (EPCs), derived from bone marrow,
      contribute to vessel repair and neovascularization. Because uremia is a state of
      endothelial dysfunction associated with high cardiovascular mortality, as well as
      a state of reduced hematopoiesis, we studied the number and function of EPCs in
      patients on long-term hemodialysis (HD) therapy. METHODS: We counted the number
      of EPCs in 20 HD patients and 16 healthy volunteers. To assess EPC function, we
      measured migratory activity, adhesion to matrix proteins, and adhesion to
      endothelial cells. Furthermore, we measured blood levels of vascular endothelial
      growth factor (VEGF) and granulocyte-macrophage colony-stimulating factor,
      factors known to influence EPC kinetics. Circulating precursor cells (CD34+ ,
      CD34+ /CD133+ , CD34+ /KDR+ cells) were counted by means of flow cytometric
      analysis. RESULTS: The number of EPCs in HD patients was significantly elevated
      compared with controls (459.7 +/- 92 versus 364.8 +/- 77.4 EPC/high-power field).
      However, migratory activity was markedly decreased in HD patients (47.5 +/- 27.7
      versus 84.7 +/- 3.2 EPC/high-power field). EPCs of HD patients showed impaired
      adhesion to extracellular matrix and endothelial cells. VEGF blood levels in HD
      patients were 2-fold greater compared with controls. The number of circulating
      CD34+ and CD34+ /133+ cells was reduced in HD patients. There were no differences
      in total numbers of CD34+ /KDR+ cells. CONCLUSION: This study shows an elevated
      number, but pronounced functional impairment, of EPCs in patients on long-term HD
      therapy. The latter may result in limited endothelial repair, which, in turn, may
      contribute to endothelial dysfunction in this particular group of patients.

PMID- 15492951
TI  - Intra-access blood flow in patients with newly created upper-arm arteriovenous
      native fistulae for hemodialysis access.
AB  - BACKGROUND: The upper-arm native arteriovenous fistula for hemodialysis (HD)
      vascular access is an important option in the long-term HD population. This
      single-center cohort study evaluated intra-access blood flow (Q AC) in 3 variants
      of newly created upper-arm fistulae. METHODS: Fifty-three patients with mature,
      working, upper-arm fistulae composed of brachial artery to cephalic vein (n =
      27), brachial artery to basilic vein (n = 13), and brachial artery to median
      antecubital vein (n = 13) fistulae were included. Nine of 13 brachio-median
      antecubital fistulae were of the Gracz type and used the deep perforating vein. Q
      AC was measured by means of ultrasound velocity dilution during HD. In brachio
      median antecubital fistulae, additional flow in the alternate draining vein was
      measured by means of duplex ultrasound, with 9 of 11 studied patients showing a
      patent alternate outflow, of whom 7 patients showed substantial flow (median, 0.7
      L/min). RESULTS: Q AC in the HD-used primary vein in brachio-median antecubital
      fistulae (0.85 L/min) was significantly less than those of brachiocephalic and
      brachiobasilic fistulae (1.4 and 1.7 L/min, respectively). However, when the
      additional flow provided by the patent alternate vein in brachio-median
      antecubital fistulae was considered, flow rates provided by all 3 variants of
      fistulae appeared similar. The inverse correlation between alternate-vein and
      primary-vein flows (r = -0.70; P = 0.017) suggested there was competitive flow
      between the 2 venous outlets. There was no instance of access recirculation.
      CONCLUSION: Upper-arm fistulae, regardless of type, provide excellent blood flows
      and should be considered routinely if a wrist fistula is not feasible. The patent
      alternate vein in the brachio-median antecubital or Gracz fistula may continue to
      drain a substantial amount of blood.

PMID- 15492952
TI  - Vascular access stenosis: comparison of arteriovenous grafts and fistulas.
AB  - BACKGROUND: Vascular access stenosis is a frequent problem in hemodialysis
      patients. There is little published literature comparing the features of stenosis
      between arteriovenous fistulas and grafts, relative outcomes of elective
      angioplasty, and clinical factors predictive of access patency after angioplasty.
      METHODS: Prospective data were collected for all patients referred for a
      fistulogram during a 2-year period because of suspected access stenosis.
      Angioplasty was performed if there was greater than 50% stenosis. For each
      procedure, we recorded the number and location of stenotic lesions, degree of
      stenosis (on a scale of 1 to 4), and ratio of access to systemic systolic
      pressure. All subsequent access procedures were tracked prospectively to
      calculate intervention-free access survival. Multivariable analysis was used to
      evaluate clinical factors affecting access patency after angioplasty. RESULTS:
      Five hundred forty-three fistulograms were obtained: 358 in grafts and 185 in
      fistulas. The likelihood of finding a significant stenosis was substantially
      lower in fistulas than grafts (39.4% versus 68.7%; P < 0.001). Among patients
      with a significant stenosis, those with fistulas were less likely to have 2 or
      more stenotic lesions (12.5% versus 33.1%; P < 0.001). After angioplasty, degree
      of stenosis (1.35 +/- 0.70 versus 1.23 +/- 0.52) and access to systemic pressure
      ratio (0.34 +/- 0.15 versus 0.32 +/- 0.14) were similar between fistulas and
      grafts. Intervention-free survival was similar for fistulas and grafts (median
      survival, 7.5 versus 6.2 months; P = 0.36). Using multivariable stepwise
      proportional hazard regression analysis, only female sex, residual access
      stenosis, and postangioplasty access pressure ratio greater than 0.4
      significantly predicted access survival (P = 0.0006). CONCLUSION: The positive
      predictive value of clinical evaluation for access stenosis is substantially
      lower for fistulas than grafts. The technical success of angioplasty and
      subsequent primary patency are similar for fistulas and grafts. Finally, female
      sex, residual stenosis, and high postprocedure access pressure ratio are each
      predictive of shorter access patency after elective angioplasty.

PMID- 15492953
TI  - Epoetin requirements predict mortality in hemodialysis patients.
AB  - BACKGROUND: Anemia is a frequent complication of end-stage renal disease. Poor
      responsiveness to epoetin therapy hampers the management of anemia. Escalating
      epoetin doses often are used to overcome epoetin resistance. The objective of
      this study is to examine the relationship between epoetin dose requirements and
      mortality. METHODS: Using United States Renal Data System administrative claims
      data, we conducted a retrospective cohort study of 94,569 prevalent hemodialysis
      patients in 2000 and 2001. A Cox proportional hazard regression analysis,
      adjusted for baseline variables, and a 5-knot cubic regression spline were used
      to model the dose-response relationship between epoetin and all-cause mortality.
      RESULTS: Significant interpatient variation exists in epoetin dose requirements
      to attain defined hematocrit levels. For every hematocrit cohort studied,
      patients administered higher doses of epoetin had significantly lower hematocrit
      values and greater mortality rates. Using the cubic spline function, a
      significant nonlinear relationship between increased epoetin dose and mortality
      was found regardless of hematocrit (P < 0.0001), with the steepest increase in
      relative risk for death found after the 72.5th dose percentile. CONCLUSION:
      Epoetin dose requirement is an independent predictor of total mortality in
      hemodialysis patients after adjustment for hematocrit. Poor responders who
      continue to have low hematocrit values despite the administration of high epoetin
      doses may not necessarily benefit from more epoetin, but perhaps should be
      considered for other adjunctive therapies. In contrast to conventional wisdom,
      this study suggests that epoetin dosing requirements could provide important
      prognostic information beyond that predicted by hematocrit alone.

PMID- 15492954
TI  - Preoperative renal volumes as a predictor of graft function in living donor
      transplantation.
AB  - BACKGROUND: Nephron underdosing and donor kidney-recipient body size mismatch can
      lead to poor allograft function. The purpose of this study is to examine the
      relationship between donor kidney volume and posttransplantation graft function
      by using magnetic resonance imaging (MRI) to obtain renal volumes. Previous
      investigators used donor body surface area as a surrogate for kidney size or
      measured renal volume by using ultrasonography; both these techniques are
      inaccurate measures of renal volume. Intraoperative weights are more accurate,
      but provide information only after the transplantation is underway. More
      recently, MRI has been used preoperatively to screen living donors; these novel
      MRI techniques also provide information regarding renal size. METHODS: We
      performed a retrospective analysis of 54 patients who underwent living donor
      transplantation at our institution from 2000 to 2002. All living donors underwent
      preoperative renovascular imaging using MRI, and renal volumes were obtained for
      each donor. A transplant kidney volume-recipient body weight (Vol/Wt) ratio was
      determined for each donor-recipient pair, and patients were divided into tertiles
      corresponding to 3 groups: high (>2.7), medium (2 to 2.7), and low (<2) "nephron
      dose" ratios. RESULTS: Glomerular filtration rate (GFR) correlated with Vol/Wt
      ratio at 6 and 12 months (r = 0.46; P = 0.0005 and r = 0.41; P = 0.003). At 6
      months, mean GFRs in the low, medium, and high groups were 52.4 +/- 2.8 (SEM),
      64.5 +/- 6.2, and 82.0 +/- 4.4 mL/min, respectively (P < 0.0005). At 12 months,
      GFRs in the low, medium, and high groups were 51.6 +/- 3.6, 63.3 +/- 3.8, and
      83.9 +/- 5.4 mL/min, respectively (P < 0.0001). CONCLUSION: Transplantation of
      donor-recipient pairs with a Vol/Wt ratio less than 2 cm 3 /kg was associated
      with significantly worse graft function. Donor kidney volumes measured by means
      of preoperative MRI can be used to calculate Vol/Wt ratios before transplantation
      and identify patients at risk for a low GFR posttransplantation.

PMID- 15492955
TI  - Conversion to C2 monitoring of cyclosporine A exposure in maintenance kidney
      transplant recipients: results at 3 years.
AB  - BACKGROUND: It has been suggested that conversion from monitoring cyclosporine A
      (CsA) trough level to the level 2 hours after the morning dose (C2 ) may have
      clinical benefits in maintenance adult renal transplant recipients, but evidence
      supporting such a suggestion presently is very limited. METHODS: We enrolled 188
      maintenance patients to investigate the clinical impact of the adjustment of CsA
      dose according to C2 levels over 3 years (target, 800 ng/mL). RESULTS: Patient
      and graft survival rates were 100% and 98.4%, respectively. C2 monitoring led to
      a reduction in CsA dose in 49.4% of patients and an increase in more than 20% of
      patients without an increase in acute rejection risk and clinically overt
      nephrotoxicity. Patients in the greatest quartile of C2 levels showed the lowest
      serum creatinine levels (P = 0.009), the greatest creatinine clearance values (P
      = 0.0006), and the lowest prevalence of chronic allograft nephropathy (P = 0.01).
      By means of multivariate analysis, C2 levels were the most relevant independent
      predictors of graft deterioration (change in serum creatinine level from baseline
      to end of study > or =0.5 mg/dL [> or =44 micromol/L]). Receiver operating
      characteristic analysis showed an inflection point of mean C2 level versus risk
      for graft deterioration at less than 661 ng/mL. CONCLUSION: In maintenance renal
      transplant recipients, conversion to C2 monitoring is a seemingly safe option
      with good graft performance after 3 years. Mean C2 levels greater than 661 ng/mL
      seem to be associated with better long-term graft function and a lower prevalence
      of biopsy-proven chronic allograft nephropathy, at least during a 3-year follow
      up.

PMID- 15492956
TI  - Patients who try our patience.
AB  - The outpatient dialysis industry is experiencing a dramatic growth in new
      patients. A shortage of professional nephrology staff, coupled with increasing
      frustration with the system on the part of a number of dialysis patients,
      contributes to an environment of frustration and negative behaviors. The dialysis
      industry lacks concise or practical definitions to describe these behaviors and
      respond with appropriate interventions. Patients may be labeled improperly and
      then discharged inappropriately and involuntarily. The TransPacific Renal
      Network, a nonprofit agency supported with funds from the Centers for Medicare
      and Medicaid Services, convened a volunteer multidisciplinary work group to
      address this issue. The group's tasks were to develop behavioral definitions
      specific to dialysis therapy that could be understood easily by any dialysis
      staff member, classify these definitions into at-risk categories, examine the
      parameters of a zero-tolerance policy, and provide objective pathways to guide
      staff interventions.

PMID- 15492957
TI  - An unusual form of crystal-forming chronic interstitial nephritis following long
      term exposure to tosufloxacin tosilate.
AB  - Fluoroquinolones are known to cause acute renal failure because of interstitial
      nephritis with or without epithelioid granulomas. We report the first case of
      slowly progressive renal failure caused by crystal-forming chronic interstitial
      nephritis with non-Langerhans' cell histiocytosis after long-term exposure to a
      fluoroquinolone, tosufloxacin tosilate. Lesions consisted of spindle- to cuboidal
      shaped histiocytes with minimal collagenous matrix and low-level lymphocyte
      infiltration replacing normal tubulointerstitial structure of the kidney.
      Histiocytes were positive for CD68, but negative for S-100, suggesting they were
      derived from macrophages. There were numerous rhomboid- to needle-shaped crystal
      deposits in the cytoplasm of histiocytes, which showed bright birefringence under
      polarized light. No immunoglobulin deposits were seen in the kidney, and no
      evidence of paraproteinemia/lymphoproliferative diseases was identified in this
      patient. Despite a negative drug lymphocyte-stimulating test result using
      tosufloxacin tosilate, withdrawal of the drug and treatment with steroids
      gradually improved renal function. In this report, we describe the clinical
      course and histopathologic findings of this patient and discuss the possible
      pathogenesis.

PMID- 15492958
TI  - Hemoperitoneum in a patient with ANCA-associated polyangiitis syndrome.
AB  - Antineutrophil cytoplasmic antibody-associated vasculitides often cause small
      vessel vasculitis, usually involving the kidney. Involvement of other organ
      systems and medium to large arteries is recognized, but free-vessel rupture is
      rare. A case of a man with classic renal involvement caused by microscopic
      polyangiitis associated with multiple episodes of hemoperitoneum secondary to
      splanchnic vasculitis is described. Although his renal vasculitis responded to
      conventional immunosuppressive treatment, relentless progression of splanchnic
      vasculitis ultimately proved fatal.

PMID- 15492959
TI  - Successful pregnancy with nocturnal hemodialysis.
AB  - A 31-year-old woman with end-stage renal disease was referred to the Toronto
      General Hospital (Ontario, Canada) for conversion from conventional hemodialysis
      (CHD; 4 h/session, 3 sessions/wk) to nocturnal hemodialysis (NHD; 7 h/session, 5
      to 6 treatments/wk) because of refractory hypertension. As expected, blood
      pressure control was superior with NHD therapy, and her requirement of vasoactive
      medications also decreased. To our surprise, 8 months after conversion to NHD
      therapy, she regained normal menstrual cycles. Two years after NHD therapy
      initiation, the patient became pregnant, at which time her dialysis prescription
      was changed to 7.5 h/session, 7 nights/wk. During her pregnancy, blood pressure
      was well controlled, and biochemical, hematologic, and metabolic parameters were
      targeted to physiological levels. The patient had an uncomplicated vaginal
      delivery of a healthy 3,025-g infant at 38 weeks' gestation. This case shows that
      on NHD therapy, our patient was able to resume ovulation and have an
      uncomplicated pregnancy. We speculate that augmentation of uremic clearance by
      means of NHD was pivotal in maintaining a normal nonproblematic pregnancy. Future
      studies are required to further understand the impact of intensive hemodialysis
      therapy on reproductive endocrine functions and determine the best management of
      such patients during pregnancy.

PMID- 15492960
TI  - Does lipid-lowering therapy slow progression of chronic kidney disease?

PMID- 15492961
TI  - Screening for kidney disease in adults with diabetes mellitus: don't forget serum
      creatinine.

PMID- 15492962
TI  - Hepatitis C, proteinuria, and renal insufficiency.

PMID- 15492963
TI  - An expanding flank mass in an anephric patient.

PMID- 15492966
TI  - Performance of GFR formulas in individuals with normal renal function.

PMID- 15492969
TI  - The hypothalamic-pituitary axis in men and women with chronic kidney disease.
AB  - Although the precise abnormalities that lead to failure of the hypothalamic
      pituitary-gonadal axis in men and women with chronic kidney disease (CKD) and end
      stage renal disease (ESRD) remains undefined, evidence exists for defects in both
      the hypothalamus and the pituitary. The lack of appropriate cyclic release of
      gonadotropin-releasing hormone (GnRH) by the hypothalamus leads to loss of normal
      pulsatile luteinizing hormone (LH) release by the pituitary, which results in
      impaired ovulation in women and reduced testosterone and sperm production in men.
      The cause of impaired cyclic release of GnRH is unclear, but hyperprolactinemia,
      elevated endorphins, and high levels of GnRH and LH caused by reduced clearance
      may contribute. Perturbations of the hypothalamic-pituitary-gonadaotropin axis in
      CKD lead to high rates of infertility, dysfunctional uterine bleeding, and
      impaired puberty in children. Only through additional study of the complex
      effects of CKD on the hypothalamic-pituitary-gonadal axis will the precise
      abnormalities in hormonal control of reproduction be explained.

PMID- 15492970
TI  - Outcomes associated with hypogonadism in men with chronic kidney disease.
AB  - Chronic kidney disease is commonly accompanied by disturbances in the
      hypothalamic-pituitary-gonadal axis. Such disturbances in men give rise to
      hypogonadism and low circulating testosterone levels. The deficiency in
      testosterone can contribute to clinical outcomes such as sexual dysfunction,
      decreased bone mineralization, malnutrition and decreased muscle mass, and
      anemia. The administration of androgens to nonuremic hypogonadal men is usually
      effective in treating such outcomes. By contrast, the response to therapy in
      uremic men tends to be much less predictable. This variability in response is not
      surprising, because these same clinical outcomes can be the result of other
      aspects of the uremic state or the comorbid conditions that are frequently
      present in men with chronic kidney disease. Although further studies are needed,
      testosterone therapy may prove most useful as an adjunct to other more general
      therapies designed to address the uremic state.

PMID- 15492971
TI  - Treatment of hypogonadism in men with chronic kidney disease.
AB  - Hypogonadism is common among men with chronic kidney disease, but few studies
      have directly assessed the effects of testosterone replacement in this
      population. Limited information suggests that androgen replacement may improve
      libido and sexual function among men who are frankly hypogonadal. However, the
      threshold for normal sexual function is in the lower end of the normal range.
      Increasing serum testosterone above this level does not appear to have beneficial
      effects on sexual functioning. On the other hand, at least among healthy men, the
      dose-response curve for anabolic effects of testosterone administration appears
      to extend to testosterone levels on the high end of the normal range or above.
      Small studies have suggested that androgen treatment has anabolic effects among
      end-stage renal disease patients, even in the absence of hypogonadism. Androgens
      have potential side effects, and some preinitiation and subsequent assessment and
      monitoring are recommended to minimize these adverse effects. Recommendations for
      healthy older men appear to be reasonable for patients with chronic kidney
      disease. More research is needed to measure the effects of androgen therapy on
      various symptoms of hypogonadism as well as on overall quality of life, physical
      functioning, and survival among patients with chronic kidney disease.

PMID- 15492972
TI  - Pharmacokinetics of estrogen and progesterone in chronic kidney disease.
AB  - Estradiol, estrone, and estrone sulfate are the primary circulating estrogens in
      women; the relative amounts depend on the menopausal status of the women.
      Administration of oral estradiol or conjugated equine estrogens (CEE) results in
      a high ratio of estrone to estradiol, whereas use of nonoral routes (dermal,
      vaginal, or parenteral) results in approximately equal plasma concentrations of
      estradiol and estrone. Although estradiol and estrone are predominately
      eliminated by metabolism, and little is excreted unchanged in the urine, evidence
      indicates that chronic kidney disease (CKD) alters the pharmacokinetics of
      estradiol. Free and total estradiol plasma concentrations are higher in women
      with end-stage renal disease (ESRD) after an oral estradiol dose, but no change
      occurs in estrone concentrations. Neither estradiol nor estrone is removed in the
      dialysate. These studies suggest that women with CKD should receive a least a 50%
      reduction in oral estradiol doses. No information is available on the
      pharmacokinetics of any of the progestins in CKD. In the future, knowledge of the
      concentration effect relationship for the treatment of symptoms of menopause, as
      well as prevention of osteoporosis, will benefit all postmenopausal women who
      choose to use hormone replacement therapy.

PMID- 15492973
TI  - Outcomes associated with hypogonadism in women with chronic kidney disease.
AB  - The successful use of renal replacement therapy has resulted in longer survival
      and a population of older patients with chronic kidney disease (CKD) that
      includes patients with other significant preexisting illnesses. In this review,
      we analyze the short-term and long-term outcomes associated to persisting
      hypogonadism in CKD patients. The short-term manifestations, commonly observed in
      normal postmenopausal women, are either a rare complaint of women with CKD or are
      frequently attributed to the uremic state. These symptoms include hot flashes,
      sleep disturbances and depression, sexual dysfunction, vaginal dryness and
      atrophy, urinary incontinence, and skin aging and wrinkling. The long-term
      outcomes of hypogonadism have potentially devastating effects on bone,
      cardiovascular system, and cognitive function, which could significantly alter
      the quality of life and survival of women with stage 5 CKD (CKD-5).
      Postmenopausal osteoporosis has been recognized as an important entity associated
      with renal osteodystrophy, and efforts have begun to tackle the reduced bone
      mineral density (BMD) and increased fracture rate seen in this population.
      Similarly, cardiovascular disease represents the major cause of death in the CKD
      5 population, with a 10 to 20 times greater mortality than in the general
      population. The accumulating evidence for a possible link between osteoporosis
      and atherosclerosis is discussed, as well as new directions in the understanding
      of postmenopausal osteoporosis in the context of renal bone disease, under the
      guidance of the Global Bone and Mineral Initiative endorsed by the Kidney
      Disease: Improving Global Outcomes initiative. Nephrologists must face
      gynecological issues with their women patients and design interdisciplinary
      clinical studies that include strategies that utilize well-tested and newer drug
      regimens in the management of osteoporosis, cardiovascular disease, and other
      postmenopausal manifestations in CKD-5 patients.

PMID- 15492974
TI  - Emergence of the concept of endocrine function and endocrinology.
AB  - Endocrinology as a scientific discipline is relatively new. The term "hormone"
      was introduced in 1905, and "endocrinology" was introduced in 1909. However, its
      origins are ancient and rooted in the millennia-old practice of organotherapy,
      from its archaic religious beginnings, through early attempts to explain the
      integrated functions of the body by the philosophically sound but scientifically
      mysterious humors of Greek medicine, to its incorporation into the pharmacopoeias
      of the eighteenth century. The concept of internal secretions germinated in the
      anatomical discoveries of the Renaissance, which described ductless glands, and
      after the discovery of the circulation, came the suggestion of "internal
      secretions" into blood as organ "emanations which are useful to the body." The
      principal events that led to the emergence of endocrinology occurred in the
      latter half of the nineteenth century, from the experimental studies of Claude
      Bernard (1813-1878), the clinical observations of Thomas Addison (1793-1860), and
      the combined experimental and clinical studies of Brow-Sequard (1817-1894). The
      first decades of the twentieth century saw in sequence the isolation of crude
      organ extracts, their preparation as hormones in pure crystalline form, and their
      ultimate use in the cure of diseases that had haunted mankind thereto.

PMID- 15492975
TI  - Rationale for growth hormone therapy in children with chronic kidney disease.
AB  - Growth retardation is a common complication in children with chronic kidney
      disease. Treatable causes of growth retardation in these patients include renal
      osteodystrophy, metabolic acidosis, and inadequate nutritional intake. In
      addition, disturbances in the growth hormone-insulinlike growth factor I axis are
      a major cause of decreased growth. Administration of recombinant human growth
      hormone can overcome this problem, allowing catch-up growth and achievement of
      normal or improved adult height.

PMID- 15492976
TI  - Informing patients of the risks and benefits of hormone replacement therapy:
      nephrologists' ethical obligation.
AB  - As consultants, nephrologists are often in a position to observe and diagnose
      nonrenal illnesses as well as identify potential complications of previously
      prescribed therapies. The decision to discuss these types of issues with patients
      can be complicated by the fear of offending the patient's primary care physician.
      When such situations pose potential harm to patients, they become ethical issues
      and the nephrologist's responsibility to inform patients of potentially harmful
      exposure is clear. Given recent research findings, the use of hormone replacement
      therapy by many of the patients referred to nephrologists should be reviewed and
      discussed with the patient and the referring physician. All potential benefits
      and harms should be clearly stated.

PMID- 15492977
TI  - Nutrition interventions to address cardiovascular outcomes in chronic kidney
      disease.
AB  - The high mortality in chronic kidney disease has been linked to cardiovascular
      risk and these patients are considered at high risk. Dietary intervention can
      directly address nutritional risk factors in lipid management, calcium-phorphorus
      balance, and body composition to reduce risk of cardiovascular disease. Nutrient
      intake can also indirectly address less overt risks of dental health, nutritional
      supplements, and compliance issues.

PMID- 15492978
TI  - Effect of predialysis eating on measurement of urea reduction ratio and Kt/V.
AB  - Physicians utilize the measurement of the urea reduction ratio (URR) and Kt/V as
      surrogates for the adequacy of hemodialysis, as well as to follow the course of
      patients longitudinally. These measurements are affected by the duration of a
      dialysis treatment, the type and size of the dialyzer membrane used during the
      treatment, the blood flow rate during the treatment, and the adequacy of vascular
      access. We, and others, have noted that eating during dialysis can be associated
      with decreases in URR and Kt/V. However, there have been no previous studies that
      have examined the effects of eating before dialysis on these variables. This
      study examined the effects of eating one-third of a daily diet 2 hours before
      dialysis as opposed to fasting for a minimum of 3 hours before dialysis on the
      measured URR and Kt/V as obtained routinely in our dialysis unit. Sixty seven
      patients gave informed consent for the study, and 42 completed the protocol. No
      differences were found in URR or Kt/V when dialysis was performed 2 hours after
      eating compared with performing dialysis after at least a 3-hour fast in the
      group as a whole or in subgroup analyses of men, women, patients with diabetes,
      patients in different age groups, or patients who dialyzed on different shifts.
      Unlike intradialytic food ingestion, moderate predialysis food intake does not
      affect the measurement of dialysis adequacy as determined by URR and Kt/V.

PMID- 15492982
TI  - Prognostic significance of pRb family and p16(INK4) alterations in colorectal
      cancer: an interesting point of view in a complex net of molecular signals.

PMID- 15492983
TI  - Recommendations for the reporting of bone tumors. Association of Directors of
      Anatomic and Surgical Pathology.
AB  - The diagnosis of a bone tumor is often an arduous task, even for the most
      experienced orthopedic pathologist. As a starting point, the classification of
      bone tumors is based on a histogenetic perspective encompassing the type of
      matrix produced (or not produced) by the tumor. In general, the surgical
      pathology report should include data pertinent to the treatment and
      prognostication of an individual patient, and the report should be delivered to
      the clinician in a clear, concise fashion. Reporting of most bone tumors is
      similar and includes such information as the type of surgery done, anatomic site,
      histological type and grade of the tumor (if applicable), and the adequacy of
      surgical margins. Special emphasis is needed for those tumors with distinct and
      well-established prognostic and therapeutic features such as osteosarcoma and
      Ewing's sarcoma/peripheral neuroectodermal tumor. Our recommendation emphasizes a
      standardized protocol for these sarcomas, especially in light of evidence that
      postchemotherapeutic tumor necrosis is of prognostic significance. It is also
      important to note that radiographic imaging plays a very important, often
      critical, role in allowing the pathologist the opportunity to reach the best
      final diagnosis. This is especially true when a malignant interpretation is
      contemplated and in subtyping lesions. We recommend close collaboration between
      musculoskeletal radiologists, clinicians, and pathologists when dealing with
      complicated neoplasms of bone.

PMID- 15492984
TI  - Evidence-based medicine, medical decision analysis, and pathology.
AB  - Recent advances in molecular pathology and other technologies such as proteomics
      present pathologists with the challenge of integrating the new information
      generated with high-throughput methods with current diagnostic models based
      mostly on histopathology and clinicopathologic correlations. Parallel
      developments in the field of medical informatics and bioinformatics provide the
      technical and mathematical methods to approach these problems in a rational
      manner. However, it remains unclear whether pathologists or other medical
      specialists will become primarily responsible for the development and maintenance
      of these multivariate and multidisciplinary diagnostic and prognostic models that
      are hoped to provide more accurate, individualized patient-based information.
      Evidence-based medicine (EBM) and medical decision analysis (MDA) are relatively
      new disciplines that use quantitative methods to assess the value of information,
      differentiate fact from myth, and integrate so-called best evidence into
      multivariate models for the assessment of prognosis, response to therapy,
      selection of laboratory tests, and other complex problems that influence
      individual patient care. We review from an epistemological viewpoint the current
      approach to information in pathology and describe some of the concepts developed
      by the practitioners of EBM and MDA.

PMID- 15492985
TI  - Aberrant expression of pRb and p16(INK4), alone or in combination, indicates poor
      outcome after resection in patients with colorectal carcinoma.
AB  - This study aimed to identify potential abnormalities of retinoblastoma protein
      (pRb) and p16(INK4a) (p16) expression in resectable colorectal carcinomas (CRCs)
      and to assess the prognostic significance of pRb and p16 levels in patients with
      CRC. From July 1990 through December 1993, 117 consecutive patients with CRC
      underwent curative resection with radical lymphadenectomy. The resected specimens
      were examined immunohistochemically using monoclonal antibodies to identify
      abnormalities of pRb and p16 expression. The association of pRb and p16
      expression status with clinicopathologic features was analyzed retrospectively.
      The Cox proportional hazards model was used to identify factors independently
      affecting survival after resection. The median follow-up period was 62 months.
      Aberrant expression of pRb and p16 was identified in 82 (70%) and 87 (74%)
      patients, respectively. Coincident abnormalities of these proteins occurred in 61
      (52%) patients. Loss of pRb expression correlated with tumor site (P = 0.0119),
      whereas p16 overexpression correlated with tumor size (P = 0.0034). Coincident
      abnormalities of pRb and p16 were associated with TNM tumor stage (P = 0.011).
      The outcome after resection was worse in patients with aberrant expression of pRb
      and/or p16 than in patients with normally expressed pRb and p16 (for pRb, P =
      0.0151; for p16, P = 0.0247). Coincident abnormalities of pRb and p16 indicated
      the worst patient survival (P = 0.0310). Aberrant expression of pRb and p16
      independently affected postresection survival (relative risk = 6.312, P <0.0001;
      relative risk = 5.994, P <0.0001, respectively). Most CRCs demonstrate aberrant
      expression of pRb and/or p16 at resectable stages. Aberrant expression of pRb and
      p16, alone and in combination, heralds poor prognosis in patients with CRC.

PMID- 15492986
TI  - Identification of carboxypeptidase E and gamma-glutamyl hydrolase as biomarkers
      for pulmonary neuroendocrine tumors by cDNA microarray.
AB  - Pulmonary neuroendocrine tumors vary dramatically in their malignant behavior.
      Their classification, based on histological examination, is often difficult. In
      search of molecular and prognostic markers for these tumors, we used cDNA
      microarray analysis of human transcripts against reference RNA from a well
      characterized immortalized bronchial epithelial cell line, BEAS-2B. Tumor cells
      were isolated by laser-capture microdissection from primary tumors of 17 typical
      carcinoids, small cell lung cancers, and large cell neuroendocrine carcinomas. An
      unsupervised, hierarchical clustering algorithm resulted in a precise
      classification of each tumor subtype according to the proposed histological
      classification. Selection of genes, using supervised analysis, resulted in the
      identification of 198 statistically significant genes (P <.004) that also
      accurately discriminated between 3 predefined tumor subtypes. Two-by-two
      comparisons of these genes identified classifier genes that distinguished each
      tumor subtype from the others. Changes in expression of selected differentially
      expressed genes for each tumor subtype were internally validated by real-time
      reverse-transcription polymerase chain reaction. Expression of 2 potential
      classifier gene products, carboxypeptidase E (CPE) and gamma-glutamyl hydrolase
      (GGH), was validated by immunohistochemistry and cross-validated on additional
      archival samples of pulmonary neuroendocrine tumors. Kaplan-Meier survival
      analysis revealed that immunostaining for CPE was a statistically significant
      predictor of good prognosis, whereas GGH expression correlated with poor
      prognosis. Thus, cDNA microarray analysis led to the identification of 2 novel
      biomarkers that should facilitate molecular diagnosis and further study of
      pulmonary neuroendocrine tumors.

PMID- 15492987
TI  - Expression of vascular endothelial growth factor (VEGF) and its receptors (VEGF
      R1 [Flt-1] and VEGF-R2 [KDR/Flk-1]) in tumorlets and in neuroendocrine cell
      hyperplasia of the lung.
AB  - Pulmonary tumorlets and neuroendocrine (NE) cell hyperplasia are part of a
      continuous spectrum of NE-cell hyperplasia, going from NE hyperplasia to
      carcinoid. Vascular endothelial growth factor (VEGF) is a potent endothelial cell
      mitogen that has been shown to be increased in hypoxic lung. We hypothesized that
      tumorlets and NE-cell hyperplasia, which occur frequently in this context, were
      partly responsible for VEGF secretion. Immunohistochemical analysis of VEGF and
      both VEGF-R1 and VEGF-R2 was performed on paraffin sections of 12 lung tissues
      containing tumorlets and NE-cell hyperplasia in parallel with a control group of
      11 lung specimens. VEGF and its receptor expressions were compared in bronchial
      epithelial cells and endothelial cells in both groups. VEGF and its receptors
      were consistently expressed in tumorlets and in NE-cell hyperplasia. When
      compared with control group lungs, the staining score for VEGF in lung bearing
      tumorlets was significantly higher in endothelial cells, but was not different in
      bronchial epithelial cells. VEGF-R1 expression was significantly increased both
      on bronchial epithelial cells (P = 0.001) and endothelial cells (P = 0.006), and
      VEGF-R2 expression was significantly increased on endothelial cell (P = 0.044).
      There was a significant positive correlation between the level of expression of
      VEGF and VEGF-R1 (P = 0.04) in both control groups and lung bearing tumorlets,
      but there was no significant correlation between VEGF and VEGF-R2 expression (P =
      0.1). We concluded that VEGF is highly expressed in localized NE cell
      proliferations without potential of malignancy and might participate in local
      development of fibrosis.

PMID- 15492988
TI  - Implication of tumstatin in tumor progression of human bronchopulmonary
      carcinomas.
AB  - The NC1 domain of alpha3 chain of type IV collagen, namely tumstatin, has been
      shown to display specific anti-angiogenic properties by inhibiting endothelial
      cells' proliferation and inducing their apoptosis via an interaction with
      alphavbeta3 integrin. Until now, the tumstatin anti-angiogenic effect has only
      been shown by in vitro studies or mouse xenograft experiments. In the present
      study, we examined the expression of tumstatin in relationship with tumor
      vascularization in 34 bronchopulmonary human carcinomas. We observed a clear
      association between tumstatin expression and tumor vascularization. Indeed, a
      strong expression of tumstatin in the tumor environment correlated with a mildly
      developed vascular network. In contrast, tumstatin was absent or poorly detected
      in highly vascularized tumors. Moreover, alphavbeta3 integrin and tumstatin
      colocalized in capillary endothelial cells, suggesting a potential interaction
      between these 2 molecules. Thus, our results plead in favor of an in vivo anti
      angiogenic effect of tumstatin. This factor, largely expressed in well
      differentiated lung carcinomas, could indeed reduce tumor vascularization and
      thereby limit tumor progression.

PMID- 15492989
TI  - Myxoid epithelioid gastrointestinal stromal tumor (GIST) with mast cell
      infiltrations: a subtype of GIST with mutations of platelet-derived growth factor
      receptor alpha gene.
AB  - We analyzed 30 gastrointestinal stromal tumors (GISTs) that were
      immunohistochemically weak or negative for KIT. Histologically, all 30 GISTs
      consisted of epithelioid tumor cells in at least a part of the tumor. The tumor
      cells showed different morphologies and arranged themselves in different
      histological patterns. In 20 of the 30 GISTs, round or oval epithelioid tumor
      cells often showed a less cohesive pattern of growth and showed eosinophilic
      cytoplasm and peripherally placed nuclei with myxoid stroma, whereas in the
      remaining 10 cases, tumor cells were arranged in a more cohesive pattern without
      myxoid stroma. The former type of tumors is called myxoid epithelioid GISTs in
      this study. Subsequent mutational analyses showed that the platelet-derived
      growth factor receptor alpha (PDGFRA) gene mutations in exon 12 or exon 18 were
      identified in 20 (66.7%) of the 30 GISTs, and especially in 18 (90%) of the 20
      myxoid epithelioid GISTs. Moreover, 17 (85%) of the 20 myxoid epithelioid GISTs
      were accompanied by mast cell infiltrations within the tumor nodules. In the
      remaining cases, 2 (6.7%) of the 30 GISTs had c-kit gene mutations in exon 11,
      and no mutation was found in 8 (26.7%) of 30 GISTs. None of the patients with
      myxoid epithelioid GISTs died of disease. These results suggest that myxoid
      epithelioid GISTs are a distinct subtype of GISTs that are closely correlated
      with the PDGFRA gene mutation and that recognition of such histological
      characteristics should be helpful for molecular subclassification of GISTs that
      are important for molecular targeting therapy by imatinib mesylate (STI571).

PMID- 15492990
TI  - Expression of human telomerase reverse transcriptase in gastrointestinal stromal
      tumors occurs preferentially in malignant neoplasms.
AB  - Telomerase is expressed in many human cancers and cell lines and is thought to
      contribute to their immortality. To date, little is known about the expression of
      telomerase in nonepithelial tumors. The objective of this study was to evaluate
      the expression of human telomerase reverse transcriptase (hTERT) in
      gastrointestinal stromal tumors (GISTs). Twenty-three GISTs (9 low malignant
      potential, 10 primary malignant, and 4 intra-abdominal recurrences) were
      evaluated for hTERT expression by using immunohistochemistry on tissue
      microarray. Tissue blocks were retrieved, and hematoxylin and eosin stains were
      performed to evaluate the histological tumor type. All cases were strongly
      positive for KIT (CD117). Immunohistochemistry for hTERT was performed. Eight of
      9 cases of the low malignant potential group were negative for hTERT
      immunoexpression, whereas all malignant GISTs showed positive staining that
      varied from weak to strong immunoreactivity. Six of 10 cases of the primary
      malignant GISTs were strongly positive for hTERT. The remaining cases (4/10)
      showed weak staining. All recurrent GISTs (4/4) showed strong positive
      immunostaining for hTERT. One malignant case was weakly positive for hTERT, but
      its recurrence was strongly positive. These results suggest that hTERT expression
      occurs preferentially in malignant tumors and that telomerase activity may occur
      during the progression of GISTs. Immunohistochemical staining for hTERT may be a
      useful marker for the prognostication of GISTs.

PMID- 15492991
TI  - Calicivirus infection in pediatric small intestine transplant recipients:
      pathological considerations.
AB  - Human calicivirus (HuCV), a common cause of mild gastroenteritis in the general
      population, produces a prolonged diarrheal illness in pediatric recipients of
      small intestinal transplant (IT). By use of reverse-transcription polymerase
      chain reaction to detect the viral RNA polymerase gene in stool and tissue from
      gastrointestinal biopsies, 5 pediatric IT recipients with high-volume diarrhea
      were diagnosed with HuCV enteritis. Histopathologic findings of biopsies obtained
      at different gastrointestinal sites were studied retrospectively to identify
      characteristic features of HuCV enteritis and to distinguish these changes from
      rejection. Controls were 8 pediatric IT recipients with high-volume diarrhea but
      negative HuCV reverse-transcription polymerase chain reaction assays during the
      same time period. All HuCV biopsies showed increased mononuclear infiltrates in
      the lamina propria and villous blunting. Reactive disarray of surface epithelial
      cells and increased apoptosis in the surface epithelium and superficial lamina
      propria were characteristic features (in 4/5 patients). Increased glandular
      apoptosis was also present in 3/5 patients. Findings were more pronounced in
      jejunal allograft than ileal allograft, and were present in both graft and native
      bowel. In comparison with the control group, the architectural changes, surface
      epithelial reactive changes, and superficial apoptosis were characteristic of
      HuCV enteritis, while the presence of glandular apoptosis was a feature shared
      with cases of mild acute cellular rejection HuCV may cause severe allograft
      dysfunction after pediatric IT. Calicivirus infection has clinical and
      histological features that overlap with allograft rejection. Knowledge of the
      characteristic histologic features of HuCV enteritis aids in differential
      diagnosis.

PMID- 15492992
TI  - Intrasinusoidal cytotoxic CD8+ T cells in nodular regenerative hyperplasia of the
      liver.
AB  - Diffuse nodular regenerative hyperplasia (NRH) of the liver is an acquired
      architectural disturbance that can lead to portal hypertension. Although
      frequently associated with autoimmune or hematologic malignancies, its exact
      pathogenesis remains largely unknown. We observed CD8+ cytotoxic T cells in the
      liver sinusoids of 14 of 44 NRH patients and explored possible relationships
      between these lymphocytes and vascular damage. The immunophenotype of
      intrahepatic lymphocytes was determined using immunohistochemical analysis and
      endothelial injury using the terminal deoxynucleotidyl transferase-mediated
      deoxyuridine triphosphate nick-end labeling method for apoptosis combined with
      endothelial cell labeling. Controls for the quantitative analysis of liver
      infiltrating lymphocytes consisted of patients with chronic hepatitis C or normal
      liver (n = 13 and n = 6, respectively). Liver specimens from the 14 patients
      dislayed intrasinusoidal infiltrate composed of CD3+ and CD8+ lymphocytes,
      located near atrophic liver cell plates. Significantly more granzyme B+ and CD57+
      lymphocytes were observed in NRH than chronic hepatitis C samples with
      quantitatively similar CD8+ infiltrates. Double-labeling revealed apoptotic
      endothelial sinusoidal cells in CD8+ T-cell-infiltrated areas in all NRH samples
      but never in chronic hepatitis C or normal livers. T-cell receptor rearrangement
      or immunoscope analysis suggested liver-specific polyclonal or oligoclonal T-cell
      expansions. Clinical and biological characteristics of the 14 patients were
      similar to those observed in the 30 patients with NRH devoid of lymphocytic
      infiltration. We report here that CD8+ cytotoxic T cells infiltrated the liver
      sinusoids of a high percentage (32%) of NRH patients and suggest that some NRH
      cases might result from chronic, cytotoxic CD8+ T-lymphocyte targeting of
      sinusoidal endothelial cells.

PMID- 15492993
TI  - Influence of annual mammography from age 40 on breast cancer pathology.
AB  - The objective of this study was to determine the influence of annual mammography
      on pathology features of breast cancers in an invited population. We conducted a
      randomized trial of 53,890 invited and 106,971 control United Kingdom women who
      were recruited only from those aged 40 years, with central review of cancer
      histology. We compare the invasive cancer distribution for the categories of
      size, histological type, grade, and node status in subgroups of the invited
      population with that of controls. Among 1287 cancers identified in the total
      population through the end of December 1999, there are major differences among
      prevalence, incidence, interval, and lapsed-attender and nonattender subgroups
      for the distribution of cancer numbers in categories of chosen qualitative
      histological features. These reflect the biases known to affect a population
      exposed to screening. Comparing cancers from the unbiased group of the invited
      population with controls shows significant differences in distributions for size,
      grade, and node status but not histological type. Multivariate logistic
      regression shows significant reduction (odds ratio, 0.73; P = 0.043) in node
      positive status for the unbiased group. We conclude that annual mammography from
      age 40 years significantly reduces size and positive-node status of invasive
      cancers in the invited population. The potential for phenotypic drift of grade
      emphasizes the relevance of screen detection of all grades at sizes smaller than
      10 mm.

PMID- 15492994
TI  - PTEN mutations do not cause nuclear beta-catenin accumulation in endometrial
      carcinomas.
AB  - PTEN: and beta-catenin mutations constitute the predominant genetic alterations
      in endometrioid carcinomas of the endometrium. PTEN encodes a dual-specificity
      phosphatase with lipid phosphatase and protein tyrosine phosphatase activities
      that regulate both apoptosis and interactions with the extracellular matrix.
      Recent studies have associated PTEN mutations with tumorigenesis of prostate
      carcinoma via the Wnt signaling pathway, leading to nuclear beta-catenin
      accumulation. To elucidate the potential interaction of PTEN and beta-catenin in
      endometrial cancer, we performed mutation analyses of the entire PTEN gene and of
      exon 3 of the beta-catenin gene that is most frequently targeted by mutations. A
      total of 82 endometrial carcinomas comprising 62 type I endometrioid carcinomas
      and 20 type II high-grade carcinomas were investigated. In addition in a subset
      of 22 carcinomas, the intracellular beta-catenin distribution was analyzed by
      immunohistochemistry. Overall, 20 (24.4%) of 82 tumors revealed mutations in the
      PTEN gene, and 16 (19.5%) of 82, in the beta-catenin gene. Six tumors (7.3%)
      showed mutations in both the PTEN and beta-catenin gene. Mutations were mainly
      detected in endometrioid carcinomas of the endometrium. As expected, a striking
      nuclear accumulation of beta-catenin could be shown in tumors with beta-catenin
      mutations. In the vast majority of tumors with PTEN mutations, a regular staining
      pattern of the cytoplasmic and membranous compartments was found. We therefore
      conclude that, in contrast to prostate cancer, mutations in the PTEN gene seem
      not to affect cellular distribution of the beta-catenin protein in endometrial
      carcinomas.

PMID- 15492995
TI  - Death-associated protein kinase (DAP kinase) alteration in soft tissue
      leiomyosarcoma: Promoter methylation or homozygous deletion is associated with a
      loss of DAP kinase expression.
AB  - The death-associated protein kinase (DAP kinase) was initially identified as a
      positive mediator of programmed cell death induced by interferon-gamma. To
      investigate the potential role and the alteration of the DAP kinase gene in soft
      tissue leiomyosarcoma (LMS), we first searched for homozygous deletion and
      promoter hypermethylation in 45 LMSs for which genomic DNA was available, using
      differential PCR and methylation-specific PCR, respectively. Promoter methylation
      was recognized in 10 of 45 cases (22%), and homozygous deletion was detected in 3
      of 45 cases (7%). p53 mutation was detected in 11 of 45 LMS cases (24%). Cases
      with DAP kinase alteration or p53 mutation showed a close correlation with high
      French Federation of Cancer Centers grade or with poor prognosis (P = 0.0244, P =
      0.0491, respectively). Next, to determine that DAP kinase promoter methylation or
      homozygous deletion is involved in the down-regulation of DAP kinase expression,
      we examined the expression of DAP kinase protein by immunohistochemistry.
      Decreased expression of DAP kinase protein was recognized in 13 of 45 LMS cases
      (29%). Seven of 13 cases (54%) with decreased expression of DAP kinase protein
      revealed promoter methylation or homozygous deletion of DAP kinase, and the
      methylation status or homozygous deletion of its gene showed a close correlation
      with decreased DAP kinase expression (P = 0.0300). In conclusion, although DAP
      kinase alteration was relatively rare, DAP kinase alteration and/or p53 mutation
      may associate with tumor progression in soft-tissue LMSs. Furthermore, although
      further detailed analyses are necessary, promoter methylation or homozygous
      deletion status of DAP kinase may present a major alternative mechanism of a loss
      of or decrease in DAP kinase expression.

PMID- 15492996
TI  - Utility of immunohistochemistry for alpha-methylacyl-CoA racemase in
      distinguishing atrophic prostate cancer from benign atrophy.
AB  - Small atrophic prostate cancers on needle biopsy are rare and difficult to
      distinguish from benign atrophy on needle biopsy. We report on a study of 23
      needle biopsy specimens with small foci of atrophic prostate cancer from the
      consult service of one of the authors. In 19 cancer cases the atrophic component
      was pure; in 4 cases it was dominant with a minor (<5%) nonatrophic cancer
      component. These atrophic cancers and 16 cases of florid benign atrophy on needle
      biopsy were examined by immunohistochemistry for alpha-methylacyl-CoA-racemase
      (AMACR). All cases of cancer and atrophy were verified immunohistochemically with
      antibodies to basal cells (34betaE12 and p63). AMACR staining were scored as 1+
      (5% to 25% of glands expressing AMACR), 2+ (26% to 50% of glands expressing
      AMACR), or 3+ (>50% of glands expressing AMACR). Positive staining was defined as
      staining above that of surrounding benign glands. AMACR was expressed in 69.6% of
      atrophic prostate cancers (3+, 11 cases; 2+, 3 cases; 1+, 2 cases); 30.4% (7
      cases) of atrophic prostate cancer exhibited no AMACR expression. In the 4 cases
      with a few glands of ordinary (nonatrophic) prostate cancer, the nonatrophic
      cancer demonstrated more intense and a greater extent of AMACR staining. Fourteen
      cases (87.5%) of benign atrophy showed no AMACR expression. In 2 cases (12.5%) of
      benign atrophy, background immunostaining made it difficult to assess AMACR
      expression. We conclude that AMACR immunostaining alone is not sufficiently
      discriminatory in the differential diagnosis of atrophic prostate cancer versus
      benign atrophy. Atrophic prostate cancers are not as frequently or as strongly
      positive as ordinary prostate cancer. Using a panel of immunostains including
      AMACR, 34betaE12 and p63 (positive AMACR immunostaining along with negative basal
      cell markers) is recommended in the differentiation of atrophic prostate cancer
      and benign atrophy.

PMID- 15492997
TI  - Immunohistochemical analysis of tumor polyamines discriminates high-risk patients
      undergoing nephrectomy for renal cell carcinoma.
AB  - Renal cell carcinoma (RCC) is known to display a wide variation in biological
      behavior and clinical outcome. Although usual bioclinical prognostic parameters
      (eg, nuclear grade, tumor stage) are to a certain extent useful in predicting the
      outcome of RCC after radical nephrectomy, they now appear to be insufficient. The
      polyamines (spermidine, spermine, and putrescine) are ubiquitous polycations that
      are essential for cell proliferation. To support their excessive proliferation,
      cancer cells have high rates of polyamine metabolism. Indeed, malignant cells
      typically have higher polyamine levels than their normal counterparts. Before
      this report, antipolyamine antibodies that are potentially valuable tools for the
      in situ observation of polyamines had not been exploited in clinical conditions.
      In the present study, tumor tissues obtained from radical nephrectomy performed
      for RCC (n = 73) were immunostained with the anti-spermine monoclonal antibody
      Spm8-2, and the immunoreactivity was evaluated as a prognostic tool. RCC cells
      displayed various reactivity to the antibody Spm8-2 that translated into a
      heterogeneous cytoplasmic staining. The prognostic value of the labeling index
      (LI) on clinical outcome was correlated with the usual clinicopathologic
      parameters, and the cell proliferation rate was evaluated using Ki-67 labeling.
      Multiple correspondence analysis and ascending hierarchical classification were
      performed to determine significant prognostic factors. Univariate statistical
      survival analysis demonstrated that tumor size (P < .001), nuclear grade (P <
      .01), necrosis (P < .007), tumor stage (P < .004), metastasis (P < .001), Ki-67
      LI (P < .0003), and Spm8-2 immunoreactivity (P < .0001) were predictors of tumor
      related death. A positive correlation was found between Ki-67 LI and Spm8-2
      immunoreactivity (r' = .53). Multivariate analysis revealed that only Ki-67 LI
      and Spm8-2 immunoreactivity were significant independent factors in patients with
      metastases (P < .04 and <.001, respectively) and in patients without metastases
      (P < .006 and <.001, respectively). Moreover, 100% of the patients with Spm8-2
      immunoreactivity <10% were alive at the end of the follow-up. In terms of
      predictive values, Spm8-2 immunoreactivity had the highest predictive values
      (sensitivity, 89; specificity, 75; risk ratio, 11) of all clinicopathologic
      parameters. This study demonstrates that the anti-spermine monoclonal antibody
      Spm8-2 may be used at the time of radical nephrectomy as a reliable prognostic
      marker for defining RCC patients at high risk for progression.

PMID- 15492998
TI  - ALK-positive diffuse large B-cell lymphoma of the stomach associated with a
      clathrin-ALK rearrangement.
AB  - ALK-positive diffuse large B-cell lymphoma is a rare, recently characterized
      lymphoma subtype that shows granular cytoplasmic ALK expression. This report
      describes a primary gastric ALK-positive B-lineage lymphoma in which a clathrin
      (CLTC)-ALK fusion was identified by RT-PCR and direct sequencing of the
      breakpoint. This confirmed the presence of t(2;17)(p23;q23) involving the CLTC
      gene and is only the 4th report of such a translocation in this lymphoma subtype
      and the first to describe this tumor within the stomach. As in previous reports,
      immunophenotyping showed the malignant cell to be a terminally differentiated B
      lineage cell characterized by the absence of B-cell antigens and expression of
      antigens associated with plasma cell differentiation. This case confirms the
      existence of such a lymphoma subtype arising in extranodal locations and
      underscores the importance of detailed immunophenotyping and specialized
      molecular genetic investigations in confirming the diagnosis.

PMID- 15492999
TI  - Multifocal presentation of gangliocytic paraganglioma in the mediastinum and
      esophagus.
AB  - Gangliocytic paraganglioma (GP) is a rare, typically benign tumor that shows
      neuroectodermal (neurosustentacular or Schwannian and neuronal) and
      neuroendocrine differentiation. Once thought to arise exclusively in the
      periampullary region as a solitary lesion, recent reports have documented both
      origin of GP in a variety of extra-duodenal sites as well as synchronous
      multifocal presentation of the tumor. Herein, we describe the first reported case
      of simultaneous occurrence of GP in the superior mediastinum and esophagus. A
      mass in the mid-distal esophagus and a separate mass in the superior mediastinum
      at the thoracic inlet were found in a 58-year-old woman by computed tomography
      scan. Subsequent biopsy of the superior mediastinal mass showed nests of
      epithelioid tumor cells coexisting with ganglioneuromatous elements, whereas
      biopsy of the esophageal mass showed nests of epithelioid cells with interspersed
      ganglion cells. The epithelioid tumor cells showed diffuse immunohistochemical
      expression of keratin (CAM 5.2), chromogranin, and synaptophysin supporting true
      neuroendocrine differentiation; ganglion cells expressed S-100 protein and
      neurofilament protein; and the spindled elements expressed S-100 protein,
      neurofilament protein, and glial fibrillary acidic protein indicating Schwannian
      differentiation. The finding of another GP occurring outside the periampullary
      region bolsters the argument for a stem cell origin of this unusual tumor.

PMID- 15493000
TI  - Childhood malignant blue nevus of the ear associated with two intracranial
      melanocytic tumors-metastases or neurocutaneous melanosis?
AB  - Blue nevus is an uncommon pigmented tumor of dermal melanocytes that has
      traditionally been classified into common and cellular variant. It is usually a
      skin tumor in adults but can become apparent in early childhood or even be
      present at birth. Malignant blue nevus is a rare melanocytic tumor of the skin
      arising from a preexisting cellular blue nevus. We report a multinodular blue
      nevus of the left ear in an 11-year-old girl who also had 2 intracranial
      melanocytic lesions. Differential diagnosis between metastases from malignant
      blue nevus and neurocutaneous melanosis is discussed.

PMID- 15493002
TI  - Clinical use of positron emission tomography in the management of cutaneous
      melanoma.
AB  - Cutaneous melanoma is the seventh most common newly diagnosed cancer among
      Americans. It frequently metastasizes and is difficult to treat. Accurate disease
      staging is important for optimizing therapy and selecting appropriate patients
      for experimental trials. Positron emission computed tomography (PET) using 18F
      fluorodeoxyglucose (FDG) has been studied extensively since 1991 and shows great
      promise in the detection of metastatic cutaneous melanoma. Cumulative data from
      the last 13 years is reviewed in this article and suggest that FDG-PET is the
      modality of choice for evaluating patients who fit into one of four categories:
      1) individuals with a high risk for distant metastases based on extent of
      locoregional disease, 2) patients with findings that are suspicious for distant
      metastases, 3) individuals with known distant tumor deposits who still stand to
      benefit from customized therapies if new lesions are discovered or treated
      lesions regress, and 4) patients at high risk for systemic relapse who are
      considering aggressive medical therapy. Despite the overall superiority of FDG
      PET in the detection of melanoma metastases, limitations exist with respect to
      detection of small lung nodules and brain metastases, which are better evaluated
      by computed tomography and magnetic resonance imaging, respectively.

PMID- 15493003
TI  - Musculoskeletal system.
AB  - Diagnostic imaging has played a major role in the evaluation of patients with
      cancers of the bone and soft tissue. The imaging modalities have included
      radiography, computed tomography, magnetic resonance imaging, and bone
      scintigraphy. Current experience suggests that functional imaging with positron
      emission tomography (PET) and [F-18]fluorodeoxyglucose (FDG) may also have an
      important role in the imaging evaluation of patients with bone and soft tissue
      sarcoma, including guiding biopsy, detecting local recurrence in amputation
      stumps, detecting metastatic disease, predicting and monitoring response to
      therapy, and assessing for prognosis. Prospective studies with large patient
      groups will be essential to define the exact diagnostic role of FDG PET in this
      clinical setting, which should also include an evaluation of the cost
      effectiveness and the short-term and long-term benefits in clinical decision
      making and management. In this article, we review the diagnostic utility of
      dedicated PET and PET combined with computed tomography imaging system in the
      evaluation of patients with bone and soft tissue malignancies.

PMID- 15493004
TI  - The reproductive tract.
AB  - Diagnostic imaging has played a major role in the evaluation of patients with the
      cancers of the reproductive tract. The imaging modalities have included
      ultrasonography, computed tomography, magnetic resonance imaging,
      hysterosalpingography, and scintigraphy with radiolabeled monoclonal antibodies.
      Positron emission tomography (PET) with [F-18]fluorodeoxyglucose also has been
      shown to be useful in the imaging evaluation of these patients. Clinical
      applications have included initial staging and posttherapy restaging of disease,
      detecting metastatic disease, differentiating posttherapy anatomic alterations
      from recurrent or residual disease, and predicting and evaluating treatment
      response. In this article, we review the diagnostic utility of dedicated PET and
      combined PET-computed tomography systems in the imaging assessment of
      reproductive tract malignancies (excluding prostate cancer) in both sexes with an
      emphasis on fluorodeoxyglucose applications.

PMID- 15493005
TI  - Positron emission tomography for prostate, bladder, and renal cancer.
AB  - Prostate cancer, renal cancer, bladder, and other urothelial malignancies make up
      the common tumors of the male genitourinary tract. For prostate cancer, common
      clinical scenarios include managing the patient presenting with 1) low-risk
      primary cancer; 2) high-risk primary cancer; 3) prostate-specific antigen (PSA)
      recurrence after apparently successful primary therapy; 4) progressive metastatic
      disease in the noncastrate state; and 5) progressive metastatic disease in the
      castrate state. These clinical states dictate the appropriate choice of
      diagnostic imaging modalities. The role of positron emission tomography (PET) is
      still evolving but is likely to be most important in determining early spread of
      disease in patients with aggressive tumors and for monitoring response to therapy
      in more advanced patients. Available PET tracers for assessment of prostate
      cancer include FDG, 11C or 18F choline and acetate, 11C methionine, 18F fluoride,
      and fluorodihydrotestosterone. Proper staging of prostate cancer is particularly
      important in high-risk primary disease before embarking on radical prostatectomy
      or radiation therapy. PET with 11C choline or acetate, but not with FDG, appears
      promising for the assessment of nodal metastases. PSA relapse frequently is the
      first sign of recurrent or metastatic disease after radical prostatectomy or
      radiation therapy. PET with FDG can identify local recurrence and distant
      metastases, and the probability for a positive test increases with PSA. However,
      essentially all studies have shown that the sensitivity for recurrent disease
      detection is higher with either acetate or choline as compared with FDG. Although
      more data need to be gathered, it is likely that these two agents will become the
      PET tracers of choice for staging prostate cancer once metastatic disease is
      strongly suspected or documented. 18F fluoride may provide a more sensitive bone
      scan and will probably be most valuable when PSA is greater than 20 ng/mL in
      patients with high suspicion or documented osseous metastases. Several studies
      suggest that FDG uptake in metastatic prostate cancer lesions reflects the
      biologic activity of the disease. Accordingly, FDG can be used to monitor the
      response to chemotherapy and hormonal therapy. Androgen receptor imaging agents
      like fluorodihydrotestosterone are being explored to predict the biology of
      treatment response for progressive tumor in late stage disease in castrated
      patients. The assessment of renal masses and primary staging of renal cell
      carcinoma are the domain of helical CT. PET with FDG may be helpful in the
      evaluation of "equivocal findings" on conventional studies, including bone scan,
      and also in the differentiation between recurrence and posttreatment changes. The
      value of other PET tracers in renal cell carcinoma is under investigation. Few
      studies have addressed the role of PET in bladder cancer. Because of its renal
      excretion, FDG is not a useful tracer for the detection of primary bladder
      tumors. The few studies that investigated its role in the detection of lymph node
      metastases at the time of primary staging were largely disappointing. Bladder
      cancer imaging with 11C choline, 11C methionine, or 11C- acetate deserves further
      study.

PMID- 15493006
TI  - The role of positron emission tomography in radiation treatment planning.
AB  - We estimate that 30% to 40% of radiation treatment plans for cancer patients are
      changed when positron emission tomography (PET) scan findings are factored into
      the plan. The most frequent changes are upstaging of disease and the finding of
      new distant metastases. When a tumor demonstrates high tracer uptake, the PET
      scan has high accuracy in staging and in determining recurrent disease. However,
      the absence of tracer uptake cannot exclude residual dormant disease. Following
      radiation therapy, a PET scan should be delayed at least 6 weeks and preferably 3
      to 4 months so that inflammation within the radiation field can dissipate. PET
      has resulted in changes in the gross tumor volume; however, the process remains
      subjective.

PMID- 15493007
TI  - 2-deoxy-fluorglucose-positron emission tomography imaging of the brain: current
      clinical applications with emphasis on the dementias.
AB  - A number of very significant advances in the field of positron emission
      tomography (PET) imaging are now beginning to have an impact on clinical PET
      brain imaging. Among the most significant advances are further improvements in
      PET scanner detectors and computers. Increasingly, more sophisticated methods of
      image analysis and quantitation are also beginning to emerge. In addition, there
      has been a very rapid introduction of newer PET radiotracers that will ultimately
      work their way into the clinical environment. Finally, there is an expanding
      interest in the potential of PET brain imaging in the evaluation of a wide
      variety of clinical neuropsychiatric conditions.

PMID- 15493008
TI  - Evolving role of positron emission tomography in the management of patients with
      inflammatory and other benign disorders.
AB  - Fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) has evolved from a
      research imaging modality assessing brain function in physiologic and pathologic
      states to a pure clinical necessity. It has been successfully used for
      diagnosing, staging, and monitoring a variety of malignancies. FDG-PET imaging
      also is evolving into a powerful imaging modality that can be effectively used
      for the diagnosis and monitoring of a certain nononcological diseases. PET has
      been shown to be very useful in the diagnosis of osteomyelitis, painful
      prostheses, sarcoidosis, fever of unknown etiology, and acquired immunodeficiency
      syndrome. Based on recent observations, several other disorders, such as
      environment-induced lung diseases, atherosclerosis, vasculitis, back pain,
      transplantation, and blood clot, can be successfully assessed with this
      technique. With the development and the introduction of several new PET
      radiotracers, it is expected that PET will secure a major role in the management
      of patients with inflammatory and other benign disorders.

PMID- 15493009
TI  - Reorganization of ZO-1 by sodium-dependent glucose transporter activation after
      heat stress in LLC-PK1 cells.
AB  - Heat stress (HS) induces activation of high-affinity sodium-dependent glucose
      transporter (SGLT1) in porcine renal LLC-PK(1) cells. In this study, we
      investigated the roles of SGLT1 activation in reorganization of zonula occludens
      1 (ZO-1), a cytosolic tight junction (TJ) protein, after HS. HS (42 degrees C, 3
      h) caused decrease in transepithelial electrical resistance (TER). Subsequent
      incubation at 37 degrees C for 12 h increased TER above pre-HS level. The
      treatment of phloridzin, a potent SGLT1 inhibitor, or the replacement of glucose
      with a nonmetabolizable glucose analog blocked the recovery of TER and increased
      the transepithelial flux of FITC-dextran (4,000 Da). Immunofluorescent staining
      of ZO-1 showed that HS diffused ZO-1 from cell contact to cytosolic sites.
      Furthermore, the fraction of ZO-1 was distributed from the Triton X-100 insoluble
      to the Triton X-100 soluble pool. After incubation at 37 degrees C for 12 h, cell
      contact and ZO-1 extractability with Triton X-100 returned to pre-HS conditions,
      but the recovery was completely prevented by phloridzin. Tyrosine kinases
      activity was increased by HS that was inhibited by phloridzin. Genistein and
      CGP77675, tyrosine kinases inhibitors, blocked the recovery of TER and increased
      the transepithelial flux of FITC-dextran. Furthermore, these inhibitors prevented
      the recovery of cell contact and ZO-1 extractability with Triton X-100 as same as
      phloridzin. These findings suggested that the activation of SGLT1 reorganized ZO
      1 mediated by elevation of tyrosine kinases activity after heat injury.

PMID- 15493011
TI  - Initiation of DNA replication at a nuclear matrix-attached chromatin fraction.
AB  - It is still unclear what nuclear components support initiation of DNA
      replication. To address this issue, we developed a cell-free replication system
      in which the nuclear matrix along with the residual matrix-attached chromatin was
      used as a substrate for DNA replication. We found out that initiation occurred at
      late G1 residual chromatin but not at early G1 chromatin and depended on
      cytosolic and nuclear factors present in S phase cells but not in G1 cells.
      Initiation of DNA replication occurred at discrete replication foci in a pattern
      typical for early S phase. To prove that the observed initiation takes place at
      legitimate DNA replication origins, the in vitro synthesized nascent DNA strands
      were isolated and analyzed. It was shown that they were enriched in sequences
      from the core origin region of the early firing, dihydrofolate reductase origin
      of replication ori-beta and not in distal to the origin sequences. A conclusion
      is drawn that initiation of DNA replication occurs at discrete sub-chromosomal
      structures attached to the nuclear matrix.

PMID- 15493010
TI  - JAK and STAT proteins are expressed and activated by IFN-gamma in rat pancreatic
      acinar cells.
AB  - The development of acute pancreatitis (AP) is triggered by acinar events, but the
      subsequent extra-acinar events, particularly a distinct immune response, appear
      to determine its severity. Cytokines modulate this immune response and are
      derived not only from immunocytes but also from pancreatic acinar cells. We
      studied whether pancreatic acinar cells were also capable of responding to
      cytokines. The JAK/STAT-pathway represents the main effector for many cytokines.
      Therefore, expression and regulation of JAK and STAT proteins were investigated
      in rat pancreatic acinar cells. Western blotting showed expression of JAK1, JAK2,
      Tyk2, and STAT1, STAT2, STAT3, STAT5, STAT6. In addition, STAT1 was reversibly
      tyrosine-phosphorylated upon the procedure of acinar cell isolation. In contrast,
      STAT3-phosphorylation occurred spontaneously after pancreas removal and was not
      reversible within 8 h. STAT1 phosphorylation was also observed upon treatment
      with IFN-gamma but not upon EGF, TNF-alpha or IL-6, and inhibited by the JAK2
      inhibitor AG-490. Immunohistochemistry revealed cytoplasmic expression of
      unphosphorylated STAT1 in untreated acinar cells and nuclear translocation of
      phosphorylated STAT1 following IFN-gamma-treatment. Interestingly, although CCK
      leads to the activation of multiple stress pathways in pancreatic acinar cells,
      we found no influence of CCK on phosphorylation of STAT1, STAT3, or STAT5 in the
      pancreas. In conclusion, our data provide further evidence that pancreatic acinar
      cells are able to interact with immune cells. Besides stimulating immune cells
      via cytokine secretion, acinar cells are in turn capable of responding to IFN
      gamma via JAK2 and STAT1 which may have an impact on the development of AP.

PMID- 15493012
TI  - Specific AHNAK expression in brain endothelial cells with barrier properties.
AB  - The blood-brain barrier (BBB) is essential for maintaining brain homeostasis and
      low permeability. Because disruption of the BBB may contribute to many brain
      disorders, they are of considerable interests in the identification of the
      molecular mechanisms of BBB development and integrity. We here report that the
      giant protein AHNAK is expressed at the plasma membrane of endothelial cells
      (ECs) forming specific blood-tissue barriers, but is absent from the endothelium
      of capillaries characterized by extensive molecular exchanges between blood and
      extracellular fluid. In the brain, AHNAK is widely distributed in ECs with BBB
      properties, where it co-localizes with the tight junction protein ZO-1. AHNAK is
      absent from the permeable brain ECs of the choroid plexus and is down-regulated
      in permeable angiogenic ECs of brain tumors. In the choroid plexus, AHNAK
      accumulates at the tight junctions of the choroid epithelial cells that form the
      blood-cerebrospinal fluid (CSF) barrier. In EC cultures, the regulation of AHNAK
      expression and its localization corresponds to general criteria of a protein
      involved in barrier organization. AHNAK is up-regulated by angiopoietin-1 (Ang
      1), a morphogenic factor that regulates brain EC permeability. In bovine cerebral
      ECs co-cultured with glial cells, AHNAK relocates from the cytosol to the plasma
      membrane when endothelial cells acquire BBB properties. Our results identify
      AHNAK as a protein marker of endothelial cells with barrier properties.

PMID- 15493013
TI  - Glioblastoma cells deficient in DNA-dependent protein kinase are resistant to
      cell death.
AB  - DNA-dependent protein kinase (DNA-PK), a nuclear serine/threonine kinase, is
      responsible for the DNA double-strand break repair. Cells lacking or with
      dysfunctional DNA-PK are often associated with mis-repair, chromosome
      aberrations, and complex exchanges, all of which are known to contribute to the
      development of human cancers including glioblastoma. Two human glioblastoma cell
      lines were used in the experiment, M059J cells lacking the catalytic subunit of
      DNA-PK, and their isogenic but DNA-PK proficient counterpart, M059K. We found
      that M059K cells were much more sensitive to staurosporine (STS) treatment than
      M059J cells, as demonstrated by MTT assay, TUNEL detection, and annexin-V and
      propidium iodide (PI) staining. A possible mechanism responsible for the
      different sensitivity in these two cell lines was explored by the examination of
      Bcl-2, Bax, Bak, and Fas. The cell death stimulus increased anti-apoptotic Bcl-2
      and decreased pro-apoptotic Bcl-2 members (Bak and Bax) and Fas in glioblastoma
      cells deficient in DNA-PK. Activation of DNA-PK is known to promote cell death of
      human tumor cells via modulation of p53, which can down-regulate the anti
      apoptotic Bcl-2 member proteins, induce pro-apoptotic Bcl-2 family members and
      promote a Bax-Bak interaction. Our experiment also demonstrated that the mode of
      glioblastoma cell death induced by STS consisted of both apoptosis and necrosis
      and the percentage of cell death in both modes was similar in glioblastoma cell
      lines either lacking DNA-PK or containing intact DNA-PK. Taken together, our
      findings suggest that DNA-PK has a positive role in the regulation of apoptosis
      in human glioblastomas. The aberrant expression of Bcl-2 family members and Fas
      was, at least in part, responsible for decreased sensitivity of DNA-PK deficient
      glioblastoma cells to cell death stimuli.

PMID- 15493014
TI  - Isolation of mutations with dumpy-like phenotypes and of collagen genes in the
      nematode Pristionchus pacificus.
AB  - The nematode Pristionchus pacificus was developed as a satellite system in
      evolutionary developmental biology and forward and reverse genetic approaches
      allow a detailed comparison of various developmental processes between P.
      pacificus and Caenorhabditis elegans. To facilitate map-based cloning in P.
      pacificus, a genome map was generated including a genetic linkage map of
      approximately 300 molecular markers and a physical map of 10,000 BAC clones.
      Here, we describe the isolation and characterization of more than 40
      morphological mutations that can be used as genetic markers. These mutations fall
      into 12 Dumpy genes and one Roller gene that represent morphological markers for
      all six P. pacificus chromosomes. Using an in silico approach, we identified
      approximately 150 hits of P. pacificus collagen genes in the available EST, BAC
      end, and fosmid-end sequences. However, 1:1 orthologs could only be identified
      for fewer than 20 collagen genes.

PMID- 15493015
TI  - CRBP-III:lacZ expression pattern reveals a novel heterogeneity of vascular
      endothelial cells.
AB  - Vascular endothelial cells are structurally and functionally heterogeneous.
      However, the molecular basis of this heterogeneity remains poorly defined. We
      used subtractive and differential screening to identify genes that exhibit
      heterogeneous expression patterns among vascular endothelial cells. One such gene
      is cellular retinol binding protein III (CRBP-III/Rbp7). Analysis of the lacZ
      knockin line for this gene (CRBP-III:lacZ) revealed a novel organ-specific
      vascular endothelial expression pattern. LacZ was expressed in vascular
      endothelial cells in heart, skeletal muscle, adipose tissues, thymus, and
      salivary gland. However, it was not detected in other tissues such as brain,
      liver, and lung. Furthermore, the expression within each organ was primarily
      restricted to small capillary endothelial cells, but could not be detected in
      larger vessels. This organ-specific vascular endothelial expression of CRPB:lacZ
      is relatively resistant to the changes of organ microenvironment. However, the
      level of expression can be modified by vitamin A deficiency. Therefore, our
      results provide novel molecular evidence for the heterogeneity of vascular
      endothelial cells.

PMID- 15493016
TI  - X-inactivation is stably maintained in mouse embryos deficient for histone methyl
      transferase G9a.
AB  - One of the two X chromosomes becomes inactivated during early development of
      female mammals. Recent studies demonstrate that the inactive X chromosome is rich
      in histone H3 methylated at Lys-9 and Lys-27, suggesting an important role for
      these modifications in X-inactivation. It has been shown that in the mouse Eed is
      required for maintenance of X-inactivation in the extraembryonic lineages.
      Interestingly, Eed associates with Ezh2 to form a complex possessing histone
      methyltransferase activity predominantly for H3 Lys-27. We previously showed that
      G9a is one of the histone methyltransferases specific for H3 Lys-9 and is
      essential for embryonic development. Here we examined X-inactivation in mouse
      embryos deficient for G9a. Expression of Xist, which is crucial for the
      initiation of X-inactivation, was properly regulated and the inactivated X
      chromosome was stably maintained even in the absence of G9a. These results
      demonstrate that G9a is not essential for X-inactivation.

PMID- 15493017
TI  - Sox10-rtTA mouse line for tetracycline-inducible expression of transgenes in
      neural crest cells and oligodendrocytes.
AB  - Using gene targeting, we inserted a high-affinity variant of the reverse
      tetracycline controlled transactivator (rtTA) into the genomic Sox10 locus. This
      rtTA transgene faithfully recapitulated Sox10 expression in the emerging neural
      crest, several of its derivatives, and in oligodendrocytes. It was furthermore
      able to induce expression of a tetracycline inducible transgenic reporter gene in
      a doxycycline-dependent manner. Induction was fast, with substantial reporter
      gene expression visible 6 h after the onset of doxycycline treatment. Shut-off,
      in contrast, exhibited delayed kinetics, which probably correlated with
      doxycycline clearance rates. This mouse provides a useful tool for generating
      tetracycline-controlled gene expression in neural crest and oligodendrocytes.

PMID- 15493018
TI  - Floxed allele for conditional inactivation of the GABAB(1) gene.
AB  - GABA(B) receptors are the G-protein-coupled receptors for the neurotransmitter
      GABA. GABA(B) receptors are broadly expressed in the nervous system. Their
      complete absence in mice causes premature lethality or--when mice are viable-
      epilepsy, impaired memory, hyperalgesia, hypothermia, and hyperactivity. A
      spatially and temporally restricted loss of GABA(B) function would allow
      addressing how the absence of GABA(B) receptors leads to these diverse
      phenotypes. To permit a conditional gene inactivation, we flanked critical exons
      of the GABA(B(1)) gene with lox511 sites. GABA(B(1)) (lox511/lox511) mice exhibit
      normal levels of GABA(B(1)) protein, are fertile, and do not display any
      behavioral phenotype. We crossed GABA(B(1)) (lox511/lox511) with Cre-deleter mice
      to produce mice with an unrestricted GABA(B) receptor elimination. These
      GABA(B(1)) (-/-) mice no longer synthesize GABA(B(1)) protein and exhibit the
      expected behavioral abnormalities. The conditional GABA(B(1)) allele described
      here is therefore suitable for generating mice with a site- and time-specific
      loss of GABA(B) function.

PMID- 15493019
TI  - Cre recombinase specificity defined by the tau locus.
AB  - We generated a transgenic mouse line (tau::Cre) by targeting the Cre to the tau
      locus (Mapt). Based on previous reports on the expression of Tau during
      development, we expected the Cre recombinase to be expressed in a neuron-specific
      and pan-neuronal manner. However, intercrosses between the tau::Cre and the Cre
      activatable reporter animals resulted in offspring with recombination either
      restricted to the nervous system or throughout the entire conceptus, indicating
      expression of Tau early in development. The percentage of neuron-specific
      excision was dependent on the Cre reporter used representing different Cre target
      sites in the mouse genome. In spite of the observed variability, our data suggest
      that the tau::Cre mouse line can be used for pan-neuronal recombination of floxed
      alleles when it is used with caution.

PMID- 15493020
TI  - Notes from the field: how a molecular geneticist got wet.

PMID- 15493021
TI  - NIR laser tissue welding of in vitro porcine cornea and sclera tissue.
AB  - BACKGROUND AND OBJECTIVE: The objective of this study was to test the hypothesis
      that an near infrared (NIR) laser system (1,455 nm) in combination with a
      motorized translational stage to control the position and speed of the laser beam
      and a shutter to control the laser exposure to the tissue being welded could be
      used to successfully weld ocular tissues. STUDY DESIGN/MATERIALS AND METHODS:
      Seventy-five porcine corneas and 23 porcine scleral tissues were welded in vitro
      in this study. The welded tissues were examined using histopathology and tensile
      strength analysis. Eight different welding conditions were analyzed for porcine
      cornea and one for sclera tissues. The tensile strength of the welded groups was
      compared to a sutured cornea control group. RESULTS: The NIR laser welding system
      provides strong, full thickness welds and does not require the use of extrinsic
      dyes, chromophores, or solders. Mean weld strengths of 0.15-0.45 kg/cm(2) were
      obtained for the cornea and 1.01 kg/cm(2) for sclera welds. The native H(2)O in
      the ocular tissue serves as an absorber of the 1,455 nm radiation and helps to
      induce the welds. CONCLUSIONS: We conclude that an NIR laser system using an
      optimal laser radiation wavelength of 1,455 nm can effectively weld cornea and
      sclera tissue and that this laser tissue welding (LTW) methodology typically
      causes minimal disruption of tissue, and thus, avoids opacities and
      irregularities in the tissue which may result in decreased visual acuity. The
      optimization of a laser welding system that leads to a strong full thickness
      tissue bond without tissue destruction, an instant seal that promotes wound
      healing, and the absence of a continued presence of a foreign substance like a
      suture, is of considerable importance to the ophthalmology medical community.
      This need is especially apparent with respect to corneal transplantation and
      fixing the position of corneal flaps in Laser-Assisted In Situ Keratomileusis
      (LASIK), a laser procedure used to permanently change the shape of the cornea.

PMID- 15493022
TI  - Intraluminal laser light source and external solder: in vivo evaluation of a new
      technique for microvascular anastomosis.
AB  - BACKGROUND AND OBJECTIVES: Current laser-assisted end-to-end anastomoses are
      performed by irradiating the vessel wall from outside after additional fixation
      with three to six sutures. These sutures are needed to provide adequate
      approximation of the vessel stumps. We present a new laser soldering technique
      that is based on an intraluminal laser light source centered in a balloon
      catheter, and external application of a solder. This technique was applied in
      vivo in order to test its feasibility under clinical conditions. STUDY
      DESIGN/MATERIALS AND METHODS: Seven white pigs were treated with a total of
      fourteen end-to-end laser-anastomoses of their saphenous arteries having outer
      diameters of 2 mm. The vessels were stented over an intraluminal balloon
      catheter, which was maximally dilated and which allowed for a precise
      approximation of the vascular stumps. An 808 nm diode laser was coupled into a
      specially designed optical fiber producing a 360 degrees radiation ring inside
      the balloon catheter. An indocyanine green (ICG) doped liquid albumin solder was
      applied on the external surface of the vascular stumps. Laser soldering was
      achieved by irradiating with a 808 nm laser diode for 75 seconds. Tightness of
      the anastomoses was evaluated by clamping the artery distal to the anastomosis
      for 1 hour, and patency was tested over an observation period of 3 hours, during
      which the animals were heparinized. Thereafter, the anastomoses were harvested
      for histomorphological examination. RESULTS: All anastomoses remained patent over
      the entire observation period. Some leakage was observed in three anastomoses,
      which was explained by a deviation of the illumination fiber from the center of
      the balloon leading to an inhomogeneous irradiation of the vessel wall. Histology
      revealed perfect adaptation of the vascular stumps. A segment of denaturated
      vascular collagen was observed, that corresponded to the irradiated, solder
      covered zone. CONCLUSION: Patent, maximally dilated and well adapted
      microvascular anastomoses could be obtained without the need of stay sutures. A
      well centered laser light source is indispensable for avoiding inhomogenous
      welding, thus causing leakage.

PMID- 15493023
TI  - Selective targeting of protein, water, and mineral in dentin using UV and IR
      pulse lasers: the effect on the bond strength to composite restorative materials.
AB  - BACKGROUND AND OBJECTIVES: Previous studies have shown that during the laser
      irradiation of dentin and bone, thermal damage can be minimized by using a highly
      absorbed laser wavelength, laser pulses shorter than the thermal relaxation time
      of the deposited laser energy at that wavelength, and the addition of a layer of
      water to the tissue surface before ablation. The objective of this study was to
      investigate the influence of laser pulse duration and wavelength with and without
      the added water layer on the bond strength of composite to laser prepared dentin
      surfaces. The specific hypothesis that was tested was that thermal damage to the
      collagen matrix in dentin compromises the bond strength to composite restorative
      materials. STUDY DESIGN/MATERIALS AND METHODS: Three laser systems were employed
      that were tuned to water, collagen, and mineral absorption with pulse durations
      less than the thermal relaxation time of the deposited energy. The surfaces of
      human dentin were irradiated by laser irradiation from free-running and Q
      switched Er:YSGG lasers, pulsed CO(2) lasers operating at 9.6-microm, and a Q
      switched Nd:YAG laser operating at 355-nm. A motion control system and a
      pressurized spray system incorporating a microprocessor controlled pulsed nozzle
      for water delivery, were used to ensure uniform treatment of the entire surface.
      Shear bond testing was used to evaluate the adhesive strength in order to access
      the suitability of laser treated surfaces for bonding. Bonded interfaces were
      examined by SEM. RESULTS: All the laser groups had significantly lower bond
      strengths than the positive acid etch control group. The highest bond strengths
      were for the short pulse (< 5-microsecond) Er:YSGG and CO(2) laser groups with
      water. Laser groups without water had significantly reduced bond strengths and
      thicker layers of thermally damaged dentin. CONCLUSIONS: Thermal damage to the
      collagen matrix profoundly influences the bond strength to composite
      restorations.

PMID- 15493024
TI  - In vivo optical coherence tomography for the diagnosis of oral malignancy.
AB  - BACKGROUND AND OBJECTIVE: Oral cancer results in 10,000 U.S. deaths annually.
      Improved highly sensitive diagnostics allowing early detection of oral cancer
      would benefit patient survival and quality of life. Objective was to investigate
      in vivo non-invasive optical coherence tomography (OCT) techniques for imaging
      and diagnosing neoplasia-related epithelial, sub-epithelial changes throughout
      carcinogenesis. STUDY DESIGN/MATERIALS AND METHODS: In the standard hamster cheek
      pouch model for oral carcinogenesis (n = 36), in vivo OCT was used to image
      epithelial and sub-epithelial change. OCT- and histopathology-based diagnoses on
      a scale of 0 (healthy) to 6 (squamous cell carcinoma, SCC) were performed at all
      stages throughout carcinogenesis by two blinded investigators. RESULTS:
      Epithelial, sub-epithelial structures were clearly discernible using OCT. OCT
      diagnosis agreed with the histopathological gold standard in 80% of readings.
      CONCLUSION: In vivo OCT demonstrates excellent potential as a diagnostic tool in
      the oral cavity.

PMID- 15493025
TI  - Healing of perforating rat corneal incisions closed with photodynamic laser
      activated tissue glue.
AB  - BACKGROUND AND OBJECTIVES: Laser-activated photodynamic biologic tissue glues may
      be useful for closing incisions in ophthalmology. We report on the use of two
      such preparations to close perforating corneal incisions in living rats. STUDY
      DESIGN/MATERIALS AND METHODS: A previously described preparation containing a
      covalent albumin-chlorin e6 (ce6) conjugate (bovine serum albumin (BSA)-ce6), and
      a novel mixture of albumin and Janus Green (BSA/JG), both activated with a 665-nm
      diode laser were used to glue mouse skin ex vivo. The optimized glues were then
      used to seal incisions in rat corneas and results were compared to control
      incisions. Rats were sacrificed at day 1, 7, and 14 and eyes tested for leaking
      pressure and examined histopathologically. RESULTS: One day after treatment eyes
      closed with BSA-ce6 had a leaking pressure (in mmHg) of 357 compared to 193 for
      control incisions (P<0.01); closure with BSA/JG gave a leaking pressure of 430
      (P<0.05 compared to BSA-ce6, and P<0.001 compared to control). Histological
      examination showed eyes sealed with BSA/JG have less inflammation present than
      untreated eyes at 7 days. CONCLUSIONS: These data demonstrate that photodynamic
      laser activated tissue glues can be used to effectively seal corneal incisions in
      living animals without thermal damage or undue inflammation.

PMID- 15493026
TI  - Ultrastructural comparison of medial collateral ligament repair after single or
      multiple applications of GaAlAs laser in rats.
AB  - BACKGROUND AND OBJECTIVES: To examine single versus multiple applications of a
      gallium aluminum arsenide (GaAlAs) laser on the ultrastructural morphology of
      surgically injured medial collateral ligaments (MCLs) in rats. STUDY
      DESIGN/MATERIALS AND METHODS: Sixteen rats were studied with 12 receiving right
      MCL transection and 4 receiving sham injury. Group 1 (n = 4) received one session
      of laser (31.6 J/cm(2)) immediately after injury. Group 2 (n = 4) received 9
      doses of transcutaneous laser (3.5 J/cm(2)). The controls (Group 3, n = 4)
      received one session of placebo laser, while the sham Group 4 (n = 4) received no
      treatment. Ultrastructural analyses were done with electron microscopy at 3
      weeks. RESULTS: The mass-averaged diameters of collagen fibril in the core and
      periphery of MCLs treated with multiple laser were larger than the control and
      those with single laser treatment (P < 0.05). However, the sham injured group had
      larger fibrils than all other groups (P < 0.05). CONCLUSIONS: The repairing MCLs
      had smaller collagen fibrils than the sham injured ligaments. Multiple laser
      treatments enhanced the collagen growth in the repairing MCLs at 3 weeks after
      injury, which are superior to a single treatment with similar dosage.

PMID- 15493027
TI  - Time-dependent hexaminolaevulinate induced protoporphyrin IX distribution after
      topical application in patients with cervical intraepithelial neoplasia: A
      fluorescence microscopy study.
AB  - BACKGROUND AND OBJECTIVES: Compared to the conventional management of cervical
      intraepithelial neoplasia (CIN) the potential advantage of photodynamic therapy
      (PDT) for the treatment of cervical human papilloma virus (HPV)-related disease
      encompasses a minimal invasive procedure with reduced risk of profuse bleeding as
      a consequence of conization, and possibly more favorable long-term results
      avoiding cervical stenosis. At present little is known about the precise time
      dependent distribution and histological localization of hexaminolaevulinate (HAL)
      induced protoporphyrin IX (PPIX) fluorescence in healthy tissue and in CIN. The
      aim of this study was to use ex vivo fluorescence microscopy to determine whether
      PPIX is selectively induced by neoplastic cells of the cervical epithelium at
      various times after topical application. STUDY DESIGN/MATERIALS AND METHODS: Cold
      cream containing 0.5% HAL was applied by means of cervical cap over various
      periods of time. We analyzed 52 healthy cervical mucosa and 84 CINs. RESULTS: At
      time delay 100 (+/-10) minutes, high epithelial fluorescence and a significant
      selectivity between epithelium and underlying lamina propria was found. By
      contrast, no significant difference between healthy and neoplastic tissues, or
      between low and high-grade epithelial dysplasia (P > or = 0.05), was observed at
      any time point. CONCLUSIONS: Application of HAL 0.5% cream to the cervix induced
      selective fluorescence in epithelial cells. The optimal ratio with a homogeneous
      PPIX distribution was obtained after 100 ( +/- 10) minutes cream application,
      which should be evaluated further for PDT.

PMID- 15493028
TI  - Enhancement of the immune response to residual intrahepatic tumor tissue by laser
      induced thermotherapy (LITT) compared to hepatic resection.
AB  - BACKGROUND AND OBJECTIVES: In contrast to hepatic resection, thermally destroyed
      autologous tumor cells remain in situ after laser-induced thermotherapy (LITT).
      The aim of the study was to evaluate the effect of LITT and hepatic resection on
      the immune response to residual intrahepatic tumor tissue and the growth of
      untreated liver metastases. STUDY DESIGN/MATERIALS AND METHODS: Two independent
      adenocarcinomas (CC531) were implanted into 60 WAG rats, one in the right
      (control tumor) and one in the left liver lobe (treated tumor). The left lobe
      tumor was treated either by LITT or partial hepatectomy. The control tumor was
      submitted to further investigation 24 hours, 96 hours, 7 days, and 10 days after
      treatment. RESULTS: Ten days after treatment, control tumor volumes were 296+/-46
      mm_ after LITT and 1,181+/-192 mm_, 1,387+/-200 mm_ after hepatic resection and
      no treatment, respectively (P<0.001). Peritoneal tumor spread was detected in
      4/20 cases after LITT and in 17/20 cases after hepatic resection. Expression of
      CD8, B7-2 (CD86), and to lesser extent MHCII, LFA1 (CD11a), and ICAM1 (CD54), was
      significantly enhanced at the invasion front of control tumors after LITT
      compared to hepatic resection. CONCLUSIONS: Our results suggest that LITT
      increases the immune response against untreated intrahepatic tumor tissue, which
      can lead to reduced tumor growth.

PMID- 15493029
TI  - Sequence- and site-specific photodissociation at 266 nm of protonated synthetic
      polypeptides containing a tryptophanyl residue.
AB  - Photodissociation at 266 nm of protonated synthetic polypeptides containing a
      tryptophanyl residue was investigated using a homebuilt tandem time-of-flight
      mass spectrometer equipped with a matrix-assisted laser desorption/ionization
      source. Efficient photodissociation of the protonated peptides was demonstrated.
      Most of the intense peaks in the laser-induced tandem mass spectra were sequence
      ions. Furthermore, sequence ions due to cleavages at all the peptide bonds were
      observed; this is a feature of the technique that is particularly useful for
      peptide sequencing. Fragmentations at both ends of the tryptophanyl residue were
      especially prevalent, which can be useful for location of the tryptophanyl
      chromophore in a peptide.

PMID- 15493030
TI  - Microbial reduction in periodontal pockets under exposition of a medium power
      diode laser: an experimental study in rats.
AB  - BACKGROUND AND OBJECTIVE: This work evaluates the application of a 810 nm diode
      laser operating in the range of 400-1,200 mW for bacterial reduction at
      periodontal treatment. The aim of this study is to examine the immediate effect
      of the diode medium power laser in reducing the bacterial concentration at
      periodontal pockets induced in Wistar rats. STUDY DESIGN/MATERIALS AND METHODS:
      Two bacterial collections were performed on each animal. Microbiological samples
      were collected before and immediately after laser irradiation. In each group of
      laser power, eight animals were used, totaling 40 animals. RESULTS: The initial
      and the final bacterial count revealed that laser irradiation induces
      considerable bacterial elimination, especially for Prevotella sp, Streptococcus
      beta-hemolitico, Fusobacterium sp, Pseudomonas sp. CONCLUSIONS: Our results
      indicate that this laser can constitute an alternative device to traditional
      infrared systems for bacterial reduction, with some advantage when economical and
      practical standpoints are considered.

PMID- 15493031
TI  - Accounting for leadtime in cohort studies: evaluating when to initiate HIV
      therapies.
AB  - Commonly reported comparisons of differences in disease progression according to
      disease staging at therapy initiation may be subject to bias if they do not
      account for the time it took the deferred group to reach the latter stage (that
      is, leadtime) and for previous events in those who initiate therapy at late stage
      (that is, unseen fast progressors). To estimate the impact of deferring
      initiation of highly active antiretroviral therapies (HAART) on time to clinical
      AIDS in the context of data from observational cohort studies, we describe a
      method that capitalizes on data from a pre-HAART period to multiply impute
      estimated leadtimes and the unseen events among fast progressors. After
      accounting for leadtime and the unseen events, data from two large cohort studies
      (N=739) indicate that deferring HAART initiation until CD4 is below 200 cells/mm3
      was detrimental compared to initiating between 201 and 350 (hazard ratio=1.97; 95
      percent confidence interval [CI] 1.09, 3.54), and that failure to account for
      leadtime resulted in a 38 per cent higher hazard ratio. In contrast, initiating
      HAART between 201 and 350 did not increase the hazard of AIDS compared to
      initiating with CD4 between 351 and 500 cells/mm3 (hazard ratio=0.70; 95 per cent
      CI 0.35, 1.42). Methods presented here offer an approach to analysing prevalent
      cohort studies and provide procedures to maximize the usefulness of observational
      data.

PMID- 15493032
TI  - Minimization of sample size when comparing two small probabilities in a non
      inferiority safety trial.

PMID- 15493033
TI  - Dental bleaching efficacy with diode laser and LED irradiation: an in vitro
      study.
AB  - BACKGROUND AND OBJECTIVES: Bleaching techniques achieved significant advances
      with the use of coherent or incoherent radiation sources to activate the
      bleaching agents. This in vitro study compares the whitening efficacy of LED and
      diode laser irradiation using the two agents Opalescence X-tra and HP Whiteness.
      STUDY DESIGN/MATERIALS AND METHODS: A total of 60 bovine incisors were randomly
      divided into six groups, three for each bleaching agent, receiving only agent,
      agent and LED (wavelength 470 nm), agent and 1.6 W diode laser (808 nm). The
      results of the irradiations were characterized using the CIEL*a*b* system.
      RESULTS: Significant differences in the chroma value are obtained for the two
      whitening agents and for the different light sources. In terms of lightness, the
      association of Laser and Whiteness HP bleaching gel showed significantly better
      results than when the same agent was used alone or in combination with LED.
      CONCLUSIONS: Best overall results are obtained with the Whiteness HP and Laser
      association.

PMID- 15493034
TI  - Fungicidal effect of diode laser irradiation in patients with denture stomatitis.
AB  - BACKGROUND AND OBJECTIVE: Denture stomatitis (DS) is a common inflammatory
      condition that affects denture wearers. The aim of this study was to examine, in
      vivo, the effect of diode laser irradiation on fungal growth in both the palatal
      mucosa and in denture base materials, in denture wearing patients. STUDY
      DESIGN/MATERIALS AND METHODS: In total, 70 patients with clinical study design
      evidence of DS participated in this parallel, single blind, and placebo
      controlled study. The subjects were randomly assigned to one of four different
      treatment regimens: (1) irradiation with a 685 nm wavelength laser for 10 minutes
      (30 mW); (2) irradiation with a 830 nm wavelength laser for 5 minutes (60 mW). A
      semiconductor diode laser, BTL-2000 (BTL-2 Dravotnicka Technika, Prague, Czech
      Republic), was used in both treatment cases using an energy density of 3.0
      J/cm(2) and a continuous working mode for five consecutive days; (3) placebo-sham
      irradiation of patients; (4) antimicotic-self treatment of patient's palatal
      mucosa with an antifungal oral gel and the use of an antiseptic solution for
      their dentures. The effect of laser light on fungal growth in vivo was evaluated
      after final treatment using the swab method and a semi-quantitative estimation of
      Candida albicans colonies cultivated on agar plates. RESULTS: A fungicidal effect
      was achieved in the laser treated and antimicotic treated groups, whereas most
      subjects in the placebo group were found to have unchanged conditions on both
      their palate (P = 0,004) and dentures (P < 0,001). CONCLUSIONS: Light from a low
      power laser (LLLT) may be valuable in the treatment of DS. This is of great
      importance since the rate of recurrence of disease is high, whereas an optimal
      treatment modality has not yet been found.

PMID- 15493035
TI  - Comparative transcriptional profiling of two human embryonic stem cell lines.
AB  - Human embryonic stem cells (ESCs) have generated enormous interest due to their
      ability to self-renew and produce many different cell types. In conjunction with
      microarray technology, human ESCs provide a powerful tool for employing a systems
      based approach to deciphering the molecular mechanisms that control pluripotency
      and early development. Recent work has focused on defining "stemness" and
      pluripotency based on different experimental and analytical approaches in both
      mouse and human ESCs. Using a mixed linear model statistical approach, we report
      a stringent direct comparison between data sets obtained from two human ESCs
      (BG01 and H1) in order to obtain a list of genes that are enriched in ESCs. In
      addition, we used another pluripotent population derived from BG01 ESCs to obtain
      a list of genes that we consider important to the maintenance of pluripotency. A
      total of 133 genes overlapped between the three pluripotent populations. A
      majority of the 133 genes were classified under the key functional categories of
      cell-cycle regulation, signaling, and regulation of transcription. Key genes
      expressed were Oct4, Sox2, LeftyA, and Fgf2. Also found to be enriched in all
      three populations is FLJ10713, a gene encoding a hypothetical protein of unknown
      function that has been shown in earlier studies to possess a homolog in mouse
      ESCs and also to cluster tightly with Oct4 in human ESCs. Although there were
      many genes unique to each pluripotent population, they shared similarities based
      on functional ontologies that define pluripotency. The significance of our
      studies underscores the need for direct comparison of stem cell populations that
      share biological similarities using uniform stringent analytical approaches, in
      order to better define pluripotency. Our findings have important implications for
      the maintenance of pluripotency and in developing directed differentiation
      strategies for various regenerative applications.

PMID- 15493036
TI  - Purine nucleoside phosphorylase and fludarabine phosphate gene-directed enzyme
      prodrug therapy suppresses primary tumour growth and pseudo-metastases in a mouse
      model of prostate cancer.
AB  - Gene-directed enzyme prodrug therapy based on the E. coli purine nucleoside
      phosphorylase (PNP) gene produces efficient tumour cell killing. PNP converts
      adenosine analogs into toxic metabolites that diffuse across cell membranes to
      kill neighbouring untransduced cells (PNP-GDEPT). Interference with DNA, RNA and
      protein synthesis kills dividing and non-dividing cells, an important
      consideration for slow-growing prostate tumours. This study examined the impact
      of administering PNP-GDEPT into orthotopically grown RM1 prostate cancers (PCas)
      on the growth of lung pseudo-metastases of immunocompetent mice. C57BL/6 mice
      bearing orthotopic RM1 PCas received a single intraprostatic injection of OAdV220
      (10(10) particles), a recombinant ovine atadenovirus containing the PNP gene
      controlled by the Rous Sarcoma virus promoter, followed by fludarabine phosphate
      (approximately 600 mg/m(2)/day) administered intraperitoneally (ip) once daily
      for 5 days. Pseudo-metastases were induced 2 days after intraprostatic vector
      administration by tail-vein injection of untransduced RM1 cells. Mice given PNP
      GDEPT showed a significant reduction both in prostate volume (approximately 50%)
      and in lung colony counts (approximately 60%). Apoptosis was increased two-fold
      in GDEPT-treated prostates compared with controls (P < 0.01), but was absent in
      the lungs. Staining for proliferating cell nuclear antigen (PCNA) indicated that
      proliferation of both RM1 prostate tumours (P < 0.01) and lung colonies (P <
      0.01) was significantly suppressed after GDEPT. Although prostate tumour immune
      cell infiltration did not differ significantly between treatments, immunostaining
      for Thy-1.2 (CD90) showed that GDEPT promoted Thy-1.2(+) cell infiltration into
      the prostate tumour site. This study showed that a single course of PNP-GDEPT
      significantly suppressed local PCa growth and reduced lung colony formation in
      the aggressive RM1 tumour model.

PMID- 15493037
TI  - A prospective evaluation of two radiotherapy schedules with 10 versus 20
      fractions for the treatment of metastatic spinal cord compression: final results
      of a multicenter study.
AB  - BACKGROUND: The optimal treatment of patients with metastatic spinal cord
      compression (MSCC) is still being debated. The current observational multicenter
      study, performed prospectively by the authors, evaluated two radiotherapy (RT)
      schedules and prognostic factors with respect to functional outcome METHODS: In
      the current study, 214 patients with MSCC were irradiated between April 2000 and
      September 2003 with 30 gray (Gy) per 10 fractions per 2 weeks (n = 110) or with
      40 Gy per 20 fractions per 4 weeks (n = 104). Motor function and ambulatory
      status were evaluated before RT and until 6 months after RT. The following
      potential prognostic factors were investigated: RT schedule, performance status,
      age, number of irradiated vertebrae, type of primary tumor, pretreatment
      ambulatory status, and length of time developing motor deficits before RT.
      RESULTS: Both groups were balanced for patient characteristics and potential
      prognostic factors. Motor function improved in 43% of patients after 30 Gy and in
      41% of patients after 40 Gy (P = 0.799). Posttreatment ambulatory rates were 60%
      and 64% (P = 0.708), respectively. A multivariate analysis demonstrated that a
      slower progression of motor deficits before RT (P < 0.001), a favorable histology
      of the primary tumor (P < 0.001), and being ambulatory before RT (P = 0.035) were
      associated with a better functional outcome. RT schedule (P = 0.269) and other
      variables had no significant impact. Acute toxicity was mild, and late toxicity
      was not observed during the period of follow-up. Follow-up was 12 (6-28) months
      in patients surviving >/= 6 months. CONCLUSIONS: Thirty gray per 10 fractions was
      preferable to 40 Gy per 20 fractions, because it was associated with similar
      outcome, less treatment time, and lower costs. The type of tumor, pretreatment
      ambulatory status, and length of time developing motor deficits before RT were
      relevant prognostic factors and should be considered in future studies.

PMID- 15493038
TI  - Initial immunoglobulin M 'flare' after rituximab therapy in patients diagnosed
      with Waldenstrom macroglobulinemia: an Eastern Cooperative Oncology Group Study.
AB  - BACKGROUND: The goal of the current study was to characterize the initial upsurge
      in immunoglobulin M (IgM) levels after treatment with rituximab in patients with
      Waldenstrom macroglobulinemia (WM). METHODS: As part of a Phase II Eastern
      Cooperative Oncology Group study, 72 patients were treated with rituximab (375
      mg/m(2) weekly for 4 weeks) between April 2000 and January 2002. IgM levels in
      these patients were measured at five separate time points so that any temporal
      changes that occurred could be characterized. RESULTS: Of the 54 patients for
      whom the relevant IgM measurements were available, 29 (54%) experienced an
      increase in IgM levels between baseline and the first scheduled postbaseline time
      point. At 2 months, 13 of 22 evaluable patients (59%) continued to have elevated
      IgM levels, and at 4 months, elevated IgM levels persisted in 4 of 15 evaluable
      patients (27%). Overall, a nonlinear trend characterized by an initial increase
      in IgM levels followed by a decrease in these levels was observed (P < 0.0001).
      CONCLUSIONS: Treating physicians should be aware that an IgM 'flare' may occur in
      up to 54% of patients treated with rituximab; however, most of these patients
      experience a decrease in IgM levels within 4 months after the initiation of
      therapy. Therefore, patients should not be discouraged from continuing to receive
      this potentially effective therapeutic agent, as responses to rituximab may
      develop slowly. Longer follow-up will reveal whether patients who experience an
      upsurge in IgM levels have poorer overall survival or shorter times to
      progression compared with patients who do not experience this IgM flare. Factors
      predicting an initial increase in IgM levels could not be identified.

PMID- 15493039
TI  - Inter-patient variation in efficacy of five oncolytic adenovirus candidates for
      ovarian cancer therapy.
AB  - BACKGROUND: Gene therapy offers a new strategy for cancer treatment. Adenoviruses
      represent the most widely used gene therapy vector and feature an excellent
      safety record. Conditionally replicative adenoviruses (CRAds) effect solid tumor
      penetration and tumor selective oncolysis and consequently offer potential
      efficacy for metastatic disease treatment. We evaluated five CRAds as candidate
      clinical agents for ovarian cancer therapy: RGDCRADcox-2R, Ad5VEGFE1,
      Ad5/3VEGFE1, Ad5-Delta24RGD, and Ad5/3-Delta24. METHODS: DNA replication by these
      five CRAds, wild-type adenovirus, and an E1-deleted control was measured in
      purified primary ovarian cancer cell spheroids by quantitative PCR. CRAd-mediated
      oncolysis was quantified in ovarian cancer cell monolayers and three-dimensional
      spheroids by cellular viability assays. The therapeutic efficacy of each CRAd was
      tested by intraperitoneal administration in mice with peritoneally disseminated
      human ovarian cancer. RESULTS: An increase in viral DNA was noted in primary
      tumor cell spheroids for all replicative viruses tested. Variation was noted in
      viral DNA replication between patient samples. All five CRAds induced remarkable
      oncolysis. They also prolonged survival in vivo compared with the wild-type
      control group. CONCLUSIONS: All five CRAds tested showed robust DNA replication,
      oncolysis, and in vivo therapeutic efficacy. Each virus has potential for
      clinical testing, and such further testing will ultimately determine its safety
      and relative usefulness. Variation of CRAd DNA replication between different
      patient samples suggests that target tissue features, such as surface receptors
      and endogenous transcription factors, may affect CRAd infectivity and
      replicativity. Evaluation of such factors may become important to optimize cancer
      therapy for individual patients.

PMID- 15493040
TI  - Heterogeneity of the immune response to adenovirus-mediated factor VIII gene
      therapy in different inbred hemophilic mouse strains.
AB  - BACKGROUND: The development of anti-factor VIII (FVIII) antibodies (inhibitors)
      is a critical concern when considering gene therapy as a potential treatment
      modality for hemophilia A. We used a hemophilia A mouse model bred on different
      genetic backgrounds to explore genetically controlled differences in the immune
      response to FVIII gene therapy. METHODS: C57BL/6 FVIII knockout (C57-FVIIIKO)
      mice were bred with normal BALB/c (BAL) mice, to generate a recombinant congenic
      BAL-FVIIIKO model of hemophilia A. Early generation adenoviral (Ad) vectors
      containing the canine FVIII B-domain-deleted transgene under the control of
      either the CMV promoter or a tissue-restricted (TR) promoter were administered to
      C57-FVIIIKO, C57xBAL(F1)-FVIIIKO crosses, and BAL-FVIIIKO mice. FVIII expression,
      inhibitor development, inflammation, and vector-mediated toxicity were assessed.
      RESULTS: In response to administration of Ad-CMV-cFVIII, C57-FVIIIKO mice attain
      3-fold higher levels of FVIII expression than BAL-FVIIIKO. All strains injected
      with Ad-CMV-FVIII displayed FVIII expression lasting only 2 weeks, with
      associated inhibitor development. C57-FVIII-KO mice that received Ad-TR-FVIII
      expressed FVIII for 12 months post-injection, whereas FVIII expression was
      limited to 1 week in C57xBAL(F1)-FVIIIKO and BAL-FVIIIKO mice. This loss of
      expression was associated with anti-FVIII inhibitor development. BAL-FVIIIKO mice
      showed increased hepatotoxicity with alanine aminotransferase levels reaching 4
      fold higher levels than C57-FVIIIKO mice. However, C57-FVIIIKO mice initiate a
      more rapid and effective cell-mediated clearance of virally transduced cells than
      BAL-FVIIIKO, as evidenced by real-time PCR analysis of transduced tissues.
      Overall, strain-dependent differences in the immune response to FVIII gene
      delivery were only noted in the adaptive response, and not in the innate
      response. CONCLUSIONS: Our results indicate that the genetic background of the
      murine model of hemophilia A influences FVIII expression levels, the development
      of anti-FVIII inhibitors, clearance of transduced cells, and the severity of
      vector-mediated hepatotoxicity.

PMID- 15493041
TI  - Long-term survival estimates for imatinib versus interferon-alpha plus low-dose
      cytarabine for patients with newly diagnosed chronic-phase chronic myeloid
      leukemia.
AB  - BACKGROUND: The authors estimated survival among patients with chronic myeloid
      leukemia for a cost-effectiveness analysis of imatinib versus interferon-alpha
      plus low-dose cytarabine (IFN+LDAC). METHODS: Two-year survival and cytogenetic
      response were determined using data from 553 patients who received first-line
      imatinib in the International Randomized Interferon versus ST571 Study (IRIS).
      Long-term survival was modeled on complete cytogenetic response (CCyR) after 2
      years. Long-term survival for patients with a CCyR was modeled using data from a
      cohort study of 317 patients with CCyRs. Long-term survival for patients without
      a CCyR was modeled using data from a trial of 275 patients who were treated with
      IFN+LDAC. Computation of lifetime survival estimates for imatinib assumed a
      proportional hazards relation between survival for an age-matched and gender
      matched cohort and survival for patients with and without a CCyR. RESULTS: For
      IRIS patients receiving imatinib, the estimated survival was 95.8% and the CCyR
      rate was 73.8%. The average residual life expectancy was estimated to be 16.71
      years for CCyR patients and 5.78 years for non-CCyR patients. The estimated life
      expectancy after treatment with imatinib was 15.30 years, compared with 9.07
      years for patients who were treated with IFN+LDAC in previous studies.
      CONCLUSIONS: Assuming the relation between CCyR and survival with interferon
      alpha holds for imatinib, higher CCyR rates with imatinib therapy will result in
      an estimated 6.23 life-years gained compared with treatment with IFN+LDAC.

PMID- 15493042
TI  - Cost-effectiveness of imatinib versus interferon-alpha plus low-dose cytarabine
      for patients with newly diagnosed chronic-phase chronic myeloid leukemia.
AB  - BACKGROUND: Despite a lack of long-term data, imatinib has become standard
      therapy for patients with newly diagnosed chronic-phase chronic myeloid leukemia
      (CML) who are not candidates for allogeneic stem cell transplantation. In the
      current study, the authors estimated the incremental cost-effectiveness of
      imatinib versus interferon-alpha plus low-dose cytarabine (IFN+LDAC) as first
      line therapy for these patients. METHODS: Data from the International Randomized
      Interferon versus STI571 Study and the literature were used to estimate lifetime
      costs, survival, and quality-adjusted survival. Survival estimates were based on
      published survival curves for patients who achieved and those who did not achieve
      a complete cytogenetic response after treatment with interferon-alpha. RESULTS:
      The mean estimated survival with first-line imatinib therapy was 15.30 years,
      compared with 9.07 years with IFN+LDAC. Undiscounted lifetime costs were
      approximately $424,600 with imatinib and $182,800 with IFN+LDAC. Using a 3%
      discount rate, the incremental survival gain with imatinib was 3.93 life-years
      and 3.89 quality-adjusted life-years (QALYs). Incremental discounted lifetime
      costs were found to be $168,100 higher with imatinib, resulting in incremental
      cost-effectiveness ratios of $43,100 per life-year saved (95% confidence interval
      [95% CI], $37,600-51,100) and $43,300 per QALY (95% CI, $38,300-49,100).
      CONCLUSIONS: The results of the current study demonstrate that compared with
      IFN+LDAC, imatinib is a cost-effective first-line therapy in patients with newly
      diagnosed chronic-phase CML.

PMID- 15493048
TI  - Plasmapheresis in the treatment of hyperthyroidism associated with
      agranulocytosis: A case report.
AB  - Plasmapheresis, also known as therapeutic plasma exchange, is used in the
      treatment of several disorders. Temporary improvement after plasmapheresis in
      cases with thyrotoxicosis has been reported. A 55-year-old woman presented with
      agranulocytosis induced by propylthiouracil and clinical signs of heart failure.
      Three sessions of plasmapheresis were performed. We observed an improvement of
      thyroid hormone levels and clinical findings as well. Plasmapheresis can be an
      option when drug treatment of thyrotoxicosis fails.

PMID- 15493049
TI  - Collection of a mobilized peripheral blood apheresis product from a patient with
      mucopolysaccharidosis type VII and subsequent CD34+ cell isolation.
AB  - The effectiveness of bone marrow transplantation for lysosomal storage diseases
      like mucopolysaccharidosis type VII (MPSVII) suggests that a gene therapy
      strategy targeting autologous hematopoietic progenitor cells could be successful.
      Given the severe systemic manifestations of MPSVII including storage disease in
      the bone and bone marrow, it was unclear whether sufficient numbers of
      hematopoietic progenitor cells (CD34+) could be mobilized into the peripheral
      circulation and subsequently purified from these patients. As reported here, G
      CSF mobilization and apheresis were successful, providing a product of 4 x 10(10)
      nucleated cells containing 0.3% CD34+ progenitors. CD34+ cells were magnetically
      separated from the product to a final purity of 85% with a 64% yield. These
      results indicate that hematopoietic progenitors can safely be gathered from an
      MPSVII patient in numbers sufficient for the trial of clinical gene therapy
      applications.

PMID- 15493050
TI  - Differentiating thrombotic microangiopathies induced by severe hypertension from
      anemia and thrombocytopenia seen in thrombotic thrombocytopenia purpura.
AB  - Thrombotic microangiopathy (TMA) is a recognized complication of malignant
      hypertension (HTN). Such patients have blood pressures > or = 200/140 mmHg but
      the condition is defined by the presence of papilledema and is frequently
      complicated by acute renal failure. Here we report two patients with severe HTN
      (systolic > or = 180 mmHg or diastolic > or = 120 mmHg), TMA, thrombocytopenia,
      renal failure, and, in one case, neurological changes (4 of 5 manifestations of
      the TTP pentad). A 50-year-old male with HTN presented with blurred vision,
      dizziness, headache, confusion, renal failure, and a TMA (PLT = 39 x 10(9)/L and
      LD = 2,781 normal <600 U/L). On presentation, BP was 214/133 mmHg and an
      ophthalmic exam demonstrated no papilledema. With HTN control over 7 days, his
      platelet count rebounded (220 x 10(9)/L), LD declined (1,730 U/L), and mental
      status improved. A 60-year-old female with diabetes, HTN, Lupus erythematosus,
      mild chronic anemia, and thrombocytopenia presented with abdominal pain,
      shortness of breath, renal failure, and a TMA (PLT = 83 x 10(9)/L and LD = 2,929
      U/L). Blood pressures were 180-210/89-111 mmHg and ophthalmic exam demonstrated
      no papilledema. With HTN control over 8 days, her platelet count rebounded (147 x
      10(9)/L), and LD declined (1,624 U/L). Although in both cases a diagnosis of TTP
      was considered because of overlap with the classic diagnostic pentad, neither
      received plasmapheresis. TTP is a diagnosis of exclusion, where there is no other
      likely diagnosis to explain the TMA. In cases of severe HTN (with or without
      papilledema), the diagnosis of TTP should be held in abeyance until the effect of
      HTN control can be assessed.

PMID- 15493051
TI  - Comparative study of plateletpheresis using Baxter CS 3000 plus and Haemonetics
      MCS 3P.
AB  - Platelet concentrates made from cell separators are used more frequently due to
      less donor exposure and leucodepletion. This retrospective study was done to
      compare plateletpheresis done on two cell separators: Baxter CS 3000 plus and
      Haemonetics MCS 3p. Plateletpheresis procedures, done from January 1997 to April
      2002, were included in the study. One hundred and seven procedures were done on
      Haemonetics MCS 3p using SDP protocol, 49 procedures were done on Haemonetics MCS
      3p using PLP protocol, and 107 were done on Baxter CS 3000 plus. Pre-procedure
      donor's platelet count and haemoglobin were comparable in all the groups.
      Platelet yield was comparable in PLP (6.44 x 10(11) platelets) and SDP (5.27 x
      10(11)) protocols, but significantly less in Baxter (4.05 x 10(11) platelets, P <
      0.001 for PLP and P < 0.05 for SDP). Efficiency of platelet removal was
      statistically significantly different in all the groups (P < 0.0001), however it
      was more in PLP (PLP-55.02%, SDP-47.38%, Baxter 38.98%). A significant number of
      products (19.51%) of Baxter failed to comply platelet count of product < or =
      2,435 x 10(9)/l compared to 5.13% in PLP and 1.23% in SDP group; 36.96% of units
      from PLP and 28% from SDP qualified for split products compared to 1.18% of
      Baxter. PLP protocol of Haemonetics MCS 3p gives better platelet yield compared
      to Baxter CS 3000 plus and SDP protocol of Haemonetics MCS 3p.

PMID- 15493052
TI  - Plasmapheresis in acute disseminated encephalomyelitis.
AB  - High-dose corticosteroid administration has been regarded as the main therapy for
      acute disseminated encephalomyelitis (ADEM). However, some patients with ADEM do
      not respond well to this treatment. We successfully used plasmapheresis to treat
      2 patients who had ADEM. We also compared our patients' symptoms and clinical
      outcomes to those from previous reports. Plasmapheresis may be indicated not only
      for severe cases that fail to improve after high-dose corticosteroid treatment
      but also for first-line treatment. Additional large, controlled, double-blinded
      trials are needed to clarify the role of plasmapheresis in ADEM.

PMID- 15493053
TI  - VEGF levels in patients with peripheral arterial occlusive disease receiving LDL
      apheresis.

PMID- 15493054
TI  - The generation of leukemic dendritic cells from acute myeloid leukemia cells is
      potentiated by the addition of CD40L at the terminal maturation stage.
AB  - Leukemic dendritic cells (DCs) that are derived from acute myeloid leukemia (AML)
      cells display low-level expression of several key molecules. We investigated the
      optimal combination of cytokines needed to generate potent leukemic DCs from AML
      cells in vitro. AML cells were cultured in the presence of the following
      combinations of cytokines: Group A, granulocyte-macrophage colony-stimulating
      factor (GM-CSF) + interleukin-4 (IL-4) + tumor necrosis factor-alpha (TNF-alpha);
      Group B, GM-CSF + IL-4 + CD40L; and Group C, CD40L addition at the terminal
      maturation point of cells that were grown as for Group A. The AML cells showed
      clear upregulation of CD80, CD83, CD86, CD40, and HLA-DR expression under all
      culture conditions, without significant differences between these groups.
      However, the addition of CD40L (as in Group C) showed a slight upregulation in
      the expression of CD83 and CD86 on leukemic DCs. The leukemic DCs in Groups A and
      B had higher allogeneic T-cell stimulatory capacities than untreated AML cells,
      and the addition of CD40L (Group C) enhanced this effect. The function of the
      cytotoxicity-stimulating autologous T cells was also augmented by the addition of
      CD40L (Group C). These results suggest that AML cells may be used to generate
      leukemic DCs using various cytokine combinations, and that the most potent,
      mature leukemic DCs are generated by the addition of CD40L to terminal-stage AML
      cultures that are grown in the presence of conventional cytokine combinations.

PMID- 15493055
TI  - Assessment of complement activation during membrane-based plasmapheresis
      procedures.
AB  - Previous studies have suggested that plasmapheresis procedures using a separation
      membrane may activate the complement system and release anaphylatoxins. This
      study determines the content in C3a/C3a(des Arg) and C5a/C5a(des Arg) in plasma
      donations obtained by the new Haemonetics Filter Core (FC) procedure and compares
      it to Baxter Autopheresis C (Auto-C). FC performs sequential blood centrifugation
      and plasma filtration on a microporous polyethersulfone membrane, while Auto-C
      removes blood cells by simultaneous gravitation and filtration on a rotating
      nylon membrane. One group of 34 donors donated on FC and two groups of 30 and 10
      donors on Auto-C. Plasma aliquots were taken from the plasma units within 30 min
      of the end of the collection procedures, frozen at < -30 degrees C and assessed
      for C3a and C5a at various time points of storage. Mean C3a/C3a(des Arg) in FC
      plasma (N = 34) was 1,151 (range: 526-2,991), 1,092 (range: 349-3498), and 507
      (range: 307-815) ng/ml at time of collection and after 6 and 12 months of
      storage, respectively. Respective C5a/C5a(des Arg) was 26.6 (range 4.9-74), 18.9
      (9.5-42.6), and 30.9 (range: 10.7-62.3) ng/ml. Mean C3a/C3a(des Arg) was higher
      in Auto-C (P < 0.001): 4,724 ng/ml (N = 10; range: 2,400-7 ,360) and > 4,149
      ng/ml (N = 30; 2,408- > 6,430) after 3 and 18 months storage, respectively. Mean
      C5a/C5a(des Arg) was 32.1 ng/ml (N = 30; range: 10.6-57.2) after 18 months of
      storage. Complement activation in FC plasmas appears limited compared to Auto-C,
      suggesting better biocompatibility of this collection device and/or a favourable
      impact of the sequential cell centrifugation/filtration technology used. Further
      studies are needed to explain differences in complement activation between
      apheresis procedures and to assess clinical impacts, if any.

PMID- 15493056
TI  - Donor tolerance and results of stimulation with G-CSF alone or in combination
      with dexamethasone for the collection of granulocytes.
AB  - Stimulation of healthy granulocyte donors allows the collection of therapeutic
      doses of granulocytes. The stimulation with G-CSF alone was compared with G-CSF
      plus dexamethasone. Blood samples were drawn at baseline, at leukapheresis, and
      at follow-up visit. Donors answered a questionnaire to evaluate side effects of
      the stimulation regimen. The combination of G-CSF and dexamethasone resulted in
      higher WBC count than G-CSF alone (39.4 +/- 7.8 vs. 34.8 +/- 8.3/nl). Glucose
      (136 +/- 45 mg/dl) and lactate dehydrogenase (195 +/- 38) increased significantly
      after stimulation with G-CSF plus dexamethasone but returned to baseline levels
      at the follow-up visit. Generally, stimulation was well tolerated by the donors.
      A higher rate of mild bone pain and headache was experienced in donors stimulated
      with G-CSF plus dexamethasone than in donors receiving G-CSF alone. Fatigue and
      myalgia were reported at similar rates in both groups. A high proportion of the
      donors stated that they would accept a further stimulation and granulocyte
      donation. At the follow-up visit, blood counts and chemistry had returned to
      normal values.

PMID- 15493057
TI  - Thrombotic thrombocytopenic purpura: 24 years of experience at the American
      University of Beirut Medical Center.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a hematological syndrome defined by
      the presence of thrombocytopenia and microangiopathic hemolytic anemia without a
      clinically apparent etiology. Patients may also suffer from fever in addition to
      neurological and renal impairment. Treatment should be initiated as soon as
      possible, otherwise this rare disease can be fatal. The main treatment options
      include therapeutic plasma exchange, fresh frozen plasma infusion, and adjuvant
      agents such as steroids and antiplatelet drugs. A search of patient records was
      carried out at the American University of Beirut Medical Center looking for
      patients who developed TTP over a 24-year period extending from 1980 to 2003.
      Relevant information was collected and analyzed. A total of 47 records were
      found. All presented with anemia and thrombocytopenia, 83% had neurological
      symptoms, 61.7% had fever and 34% had renal impairment. All patients were treated
      with a multimodality regimen including therapeutic plasma exchange, FFP infusion,
      steroids, antiplatelet agents, vincristine and others. 38 (81%) cases achieved
      complete remission. Out of these, 12 (31.6%) relapsed and responded to treatment.
      Patients who did not receive plasma exchange were more likely to relapse (P =
      0.032). A second relapse was observed in 6 cases. The overall mortality rate from
      TTP over 24 years was 21.3%. TTP remains a fatal disease. A high index of
      suspicion should, therefore, always be present. Treatment options should be
      further developed and patients should directly be referred to tertiary care
      centers.

PMID- 15493058
TI  - Sulfatases: structure, mechanism, biological activity, inhibition, and synthetic
      utility.
AB  - Sulfatases, which cleave sulfate esters in biological systems, play a key role in
      regulating the sulfation states that determine the function of many physiological
      molecules. Sulfatase substrates range from small cytosolic steroids, such as
      estrogen sulfate, to complex cell-surface carbohydrates, such as the
      glycosaminoglycans. The transformation of these molecules has been linked with
      important cellular functions, including hormone regulation, cellular degradation,
      and modulation of signaling pathways. Sulfatases have also been implicated in the
      onset of various pathophysiological conditions, including hormone-dependent
      cancers, lysosomal storage disorders, developmental abnormalities, and bacterial
      pathogenesis. These findings have increased interest in sulfatases and in
      targeting them for therapeutic endeavors. Although numerous sulfatases have been
      identified, the wide scope of their biological activity is only beginning to
      emerge. Herein, accounts of the diversity and growing biological relevance of
      sulfatases are provided along with an overview of the current understanding of
      sulfatase structure, mechanism, and inhibition.

PMID- 15493059
TI  - Power and robustness of linkage tests for quantitative traits in general
      pedigrees.
AB  - There are numerous statistical methods for quantitative trait linkage analysis in
      human studies. An ideal such method would have high power to detect genetic loci
      contributing to the trait, would be robust to non-normality in the phenotype
      distribution, would be appropriate for general pedigrees, would allow the
      incorporation of environmental covariates, and would be appropriate in the
      presence of selective sampling. We recently described a general framework for
      quantitative trait linkage analysis, based on generalized estimating equations,
      for which many current methods are special cases. This procedure is appropriate
      for general pedigrees and easily accommodates environmental covariates. In this
      report, we use computer simulations to investigate the power and robustness of a
      variety of linkage test statistics built upon our general framework. We also
      propose two novel test statistics that take account of higher moments of the
      phenotype distribution, in order to accommodate non-normality. These new linkage
      tests are shown to have high power and to be robust to non-normality. While we
      have not yet examined the performance of our procedures in the context of
      selective sampling via computer simulations, the proposed tests satisfy all of
      the other qualities of an ideal quantitative trait linkage analysis method.

PMID- 15493060
TI  - Multipoint linkage mapping using sibpairs: non-parametric estimation of trait
      effects with quantitative covariates.
AB  - Multipoint linkage analysis using sibpair designs remains a common approach to
      help investigators to narrow chromosomal regions for traits (either qualitative
      or quantitative) of interest. Despite its popularity, the success of this
      approach depends heavily on how issues such as genetic heterogeneity, gene-gene,
      and gene-environment interactions are properly handled. If addressed properly,
      the likelihood of detecting genetic linkage and of efficiently estimating the
      location of the trait locus would be enhanced, sometimes drastically. Previously,
      we have proposed an approach to deal with these issues by modeling the genetic
      effect of the target trait locus as a function of covariates pertained to the
      sibpairs. Here the genetic effect is simply the probability that a sibpair shares
      the same allele at the trait locus from their parents. Such modeling helps to
      divide the sibpairs into more homogeneous subgroups, which in turn helps to
      enhance the chance to detect linkage. One limitation of this approach is the need
      to categorize the covariates so that a small and fixed number of genetic effect
      parameters are introduced. In this report, we take advantage of the fact that
      nowadays multiple markers are readily available for genotyping simultaneously.
      This suggests that one could estimate the dependence of the generic effect on the
      covariates nonparametrically. We present an iterative procedure to estimate (1)
      the genetic effect nonparametrically and (2) the location of the trait locus
      through estimating functions developed by Liang et al. ([2001a] Hum Hered 51:67
      76). We apply this new method to the linkage study of schizophrenia to illustrate
      how the onset ages of each sibpair may help to address the issue of genetic
      heterogeneity. This analysis sheds new light on the dependence of the trait
      effect on onset ages from affected sibpairs, an observation not revealed
      previously. In addition, we have carried out some simulation work, which suggests
      that this method provides accurate inference for estimating the location of
      quantitative trait loci.

PMID- 15493061
TI  - Cellular stiffness response to external deformation: tensional homeostasis in a
      single fibroblast.
AB  - Stiffness responses of fibroblasts were measured by scanning probe microscopy,
      following elongation or compression by deformation of an elastic substrate by 8%.
      The cellular stiffness, reflecting intracellular tension acting along stress
      fibers, decreased or increased instantly in response to the elongating or
      compressing stimuli, respectively. After this rapid change, the fibroblasts
      gradually recovered to their initial stiffness during the following 2 h, and then
      stabilized. The cells did not show conspicuous changes in shape after the 8%
      deformation during the SPM measurements. Fluorescence examination for GFP-actin
      demonstrated that the structure of the stress fibers was not altered noticeably
      by this small degree of deformation. Treatment with Y-27632, to inhibit myosin
      phosphorylation and abrogate cellular contractility, eliminated the change in
      stiffness after the mechanical elongation. These results indicate that
      fibroblasts possess a mechanism that regulates intracellular tension along stress
      fibers to maintain the cellular stiffness in a constant equilibrium state.

PMID- 15493062
TI  - How useful is the fine-scale mapping of complex trait linkage peaks? Evaluating
      the impact of additional microsatellite genotyping on the posterior probability
      of linkage.
AB  - The two-stage linkage mapping protocol for complex traits (a primary genome scan
      with low marker density followed by the high-density genotyping around linkage
      peaks) is a near-universal practice. The behavior (an increase or a decrease) of
      the peak upon such fine mapping frequently leads to inferences regarding the
      veracity of the primary scan finding, namely a true, or a false, positive. We
      examined by simulation, under the null hypothesis of no linkage and the
      alternative hypothesis of true linkage, the inferences that can be made regarding
      the posterior probability of linkage given either a peak increase, or
      alternatively, a peak decrease, following fine mapping. We considered different
      models of missing genotype data, fine-mapping LOD score thresholds, and prior
      probabilities of linkage. Our simulations show that evidence for linkage can
      increase frequently upon fine mapping under both null and alternative hypotheses,
      although large increases in LOD scores are more common under the alternative
      hypothesis. Increased LOD scores accompany an increased posterior probability of
      linkage, and large LOD score changes and the presence of dominance at the trait
      locus accentuate this effect. We demonstrate that the greatest changes in the
      posterior probability of linkage occur when the genotyping data are least
      complete (and especially when parental genotypes are missing), and the LOD score
      threshold for fine mapping is relaxed.

PMID- 15493064
TI  - Mental health outcomes in older women with breast cancer: impact of perceived
      family support and adjustment.
AB  - OBJECTIVES: (1) To examine the mental health of older women with breast cancer in
      relation to support provided by, and the adjustment of, significant others
      including partners, children, and other family members or friends and (2) to
      document how often physicians address the women's significant others and the
      helpfulness of doing so. METHODS: A cross-sectional survey of newly diagnosed
      breast cancer patients aged 55 years or older (n = 222) was conducted. RESULTS:
      Partners, and in many instances children and other family members or friends,
      provided support. Support from partners and adjustment of both partners and
      children independently predicted less depression and anxiety among the study
      participants. For racial/ethnic minorities, support from, and adjustment of,
      adult children assumed particular importance. Nonetheless, women reported that
      their physicians rarely asked their significant others how they were coping (15%)
      or referred them to a support group (3%), even though both behaviors were rated
      as extremely helpful. CONCLUSION: For older women with breast cancer, both
      partners and adult children were important sources of support and their
      adjustment affected the women's mental health. Support sources and their impact
      on women's mental health varied among racial/ethnic groups, suggesting the
      importance of culturally sensitive provision of care by clinicians.

PMID- 15493063
TI  - Multiple imputation to estimate the association between eyes in disease
      progression with interval-censored data.
AB  - In many ophthalmologic studies, progression of diseases such as diabetic
      retinopathy, age-related maculopathy, cataract, and glaucoma is only noted when
      each eye is examined at intervals that commonly vary between subjects. Such data
      are often analysed using continuous time survival methods with observed
      progression assumed to occur at the end of the interval. Tied times of
      progression can lead to substantial bias in estimation of the association between
      progression in right and left eyes. We describe a multiple imputation strategy to
      create multiple data sets without ties, based on drawing interval-censored
      progression times from a parametric gamma frailty model that accounts for
      continuous and discrete covariates. We illustrate the method with data from 478
      patients with insulin-dependent diabetes mellitus who were followed for
      progression of diabetic retinopathy in the Sorbinil Retinopathy Trial. Resolution
      of tied failure times allows for valid estimation of the hazard of progression in
      one eye given the progression status of the other eye. A simulation study
      suggests that the method performs well. Results highlight the advantage of
      multiple imputation that data imputed under one model can be analysed under
      several alternative models.

PMID- 15493065
TI  - [Reference list reveals].

PMID- 15493066
TI  - [A 25-year old woman with abdominal pain and respiratory failure].
AB  - BACKGROUND: About 25% of patients with acute pancreatitis progress into severe
      pancreatitis with local and systemic complications. Local complications include
      oedema, necrosis, haemorrhage, infections, abscesses and pseudocysts. Systemic
      complications frequently involve the lungs and the kidneys in addition to
      cardiovascular dysfunction with hypotension and shock. Multi-organ failure is
      caused by a systemic inflammatory response commonly seen in necrotising
      pancreatitis, a severe condition with high mortality (about 30%). Similar
      pathogenesis is seen in sepsis or severe burns. METHODS: We report a young woman
      with acute pancreatitis and have used available literature to discuss the
      clinical picture and the pathogenesis, with an emphasis on the systemic
      complications. RESULTS AND INTERPRETATION: Systemic complications like multi
      organ failure are frequently reported in acute severe pancreatitis characterised
      by pancreatic oedema and necrosis. Our patient had abdominal pain and mild
      pancreatitis without radiological manifestations. She developed systemic
      complications with respiratory failure not previously reported in mild
      pancreatitis. Early identification of systemic complications in acute
      pancreatitis is important in order to start treatment and reduce the risk of a
      fatal outcome.

PMID- 15493067
TI  - Global pediatric cardiology.

PMID- 15493069
TI  - Usefulness of intraoperative color doppler ultrasonography in decision making
      regarding conversion of an accessory hepatic vein after a Fontan-type operation.
AB  - An accessory hepatic vein (AHV) after a Fontan-type operation will result in
      progressive desaturation if left intact. We report a case in which intraoperative
      color Doppler ultrasonography revealed the absence of AHV flow and reversed
      portal vein flow when the AHV was clamped, suggesting that simple ligation of the
      AHV would lead to liver dysfunction in the area affected. Based on the results of
      the ultrasonography evaluations, diversion of the AHV into the pulmonary
      circulation was performed without cardiopulmonary bypass, and the clinical
      outcome has been favorable.

PMID- 15493068
TI  - EYA1 mutation in a newborn female presenting with cardiofacial syndrome.
AB  - The combination of an asymmetric crying face and heart defect has been termed
      cardiofacial syndrome. This "syndrome" is etiologically heterogeneous and a
      subset of patients have 22q111.2 deletions. We present a female with Cayler's
      cardiofacial syndrome phenotype who had a frameshift mutation of the EYA1 gene.
      We conclude that EYA1 mutation represents a previously undescribed cause of
      cardiofacial syndrome.

PMID- 15493071
TI  - Hypoplastic left heart syndrome with restrictive atrial septal defect: influence
      on cardiac transplantation.

PMID- 15493070
TI  - Congenital giant aneurysm of the left innominate vein: is surgical treatment
      required?
AB  - Congenital aneurysms of the thoracic venous system are rare. In particular,
      innominate venous aneurysms are extremely rare. We describe a 16-year-old girl
      whose chest x-ray suggested a mediastinal tumor. Three-dimensional contrast
      enhancement magnetic resonance venography showed a giant sacciform aneurysm of
      the left innominate vein and dilatation of the right innominate vein. The patient
      was asymptomatic, and there were no significant physical findings. Therefore, the
      patient is being followed without surgical treatment.

PMID- 15493072
TI  - Images of desire: cognitive models of craving.
AB  - Cognitive modelling of phenomena in clinical practice allows the
      operationalization of otherwise diffuse descriptive terms such as craving or
      flashbacks. This supports the empirical investigation of the clinical phenomena
      and the development of targeted treatment interventions. This paper focuses on
      the cognitive processes underpinning craving, which is recognised as a motivating
      experience in substance dependence. We use a high-level cognitive architecture,
      Interacting Cognitive Subsystems (ICS), to compare two theories of craving:
      Tiffany's theory, centred on the control of automated action schemata, and our
      own Elaborated Intrusion theory of craving. Data from a questionnaire study of
      the subjective aspects of everyday desires experienced by a large non-clinical
      population are presented. Both the data and the high-level modelling support the
      central claim of the Elaborated Intrusion theory that imagery is a key element of
      craving, providing the subjective experience and mediating much of the associated
      disruption of concurrent cognition.

PMID- 15493073
TI  - Publishing wars.

PMID- 15493074
TI  - Smuggling for sex.

PMID- 15493075
TI  - Targeting HIF-alpha: when a magic arrow hits the bull's eye.

PMID- 15493076
TI  - The child suicide risk assessment: a screening measure of suicide risk in pre
      adolescents.
AB  - This study documents the initial reliability and validity of the Child Suicide
      Risk Assessment (CSRA) for children under the age of 13. The revised CSRA
      retained 18 of 20 original items based on item-specific psychometric data from
      140 pre-adolescents in out-of-home treatment programs. The CSRA demonstrated
      adequate internal consistency (alpha=.69) for a multi-dimensional scale (3
      factors: Worsening Depression, Lack of Support, and Death as Escape). CSRA scores
      correlated significantly with criterion measures of prior suicide attempts and
      ideations. A receiver operating characteristic (ROC) curve discriminated
      significantly between prior attempters and non-attempters and was used to select
      preliminary CSRA cut-off scores for identifying substantial suicide risk. The
      CSRA is the first screening measure of suicide risk in pre-adolescents validated
      by associations with suicide attempts as well as ideations.

PMID- 15493078
TI  - Disease-fighting vegetable medley.

PMID- 15493077
TI  - Affirming the connection: comparative findings on communication issues from
      hospice patients and hematology survivors.
AB  - The following discussion presents comparative findings from hospice patients and
      hematology survivors on the topic of talking about dying to significant others
      within their network of family and friends. The insights have been gathered from
      an Australian research program that is exploring the notion of spirituality in
      relation to serious illness. The findings document the participants' awareness,
      acceptance, and fear of dying. It documents the difficulty associated with
      talking about dying, which creates voids in relationships and deprives seriously
      ill individuals of their sense of normality, at a time when they have a strong
      need to talk and share experiences. Six specific blocks to communication are
      explored, along with as emphasis on the importance of communicating with others
      who have a similar life experience.

PMID- 15493079
TI  - Super sprouts.

PMID- 15493080
TI  - Complicated grief and the trend toward cognitive-behavioral therapy.
AB  - Recently, considerable attention has been given to the cognitive processes
      entailed in mourning. There has been a growing understanding that the death of a
      loved one forces individuals to restructure and rebuild previously held
      assumptions about the self and the world. On the basis of this conceptualization
      of grief as a period of meaning reconstruction, cognitive-behavioral therapy
      seems a fitting intervention mechanism for treating individuals with complicated
      grief. The purpose of this article is to provide an overview of the theory,
      intervention mechanisms, and research on the application of cognitive-behavioral
      therapy to grief, in general, and to non-normative grief, in particular.

PMID- 15493081
TI  - Intimacy and risky sexual behavior--what does it have to do with death?
AB  - The current series of studies was conducted to explore the interplay between
      death awareness, fear of intimacy, and unsafe sex. In Study 1 (n = 73), making
      mortality salient led to higher willingness to engage in risky sexual behaviors,
      in comparison to a control condition. In addition, only in the mortality salience
      condition, lower fear of intimacy was associated with higher sexual risk taking.
      Moreover, higher accessibility of death-related thoughts was found either
      following induction of thoughts about risky sex in Study 2 (n = 68), or upon the
      induction of thoughts about fear of intimacy in Study 3 (n = 74), in comparison
      to the induction of thoughts about a neutral theme. The findings extended Terror
      Management Theory to the realm of risky sexual behavior and are discussed in view
      of the terror management function of close relationships.

PMID- 15493082
TI  - TITAN launches with pilot programmes in Ireland and France.

PMID- 15493083
TI  - A general factor of death distress in seven clinical and non-clinical groups.
AB  - The Arabic Scale of Death anxiety (ASDA), the Death Depression Scale (DDS), and
      the Death Obsession Scale (DOS) were administered, individually, to 7 groups (n =
      765) of Egyptian normal participants (non-clinical), anxiety disorder patients,
      patients suffering from schizophrenia (males and females), and addicts (males
      only). They were generally matched as groups according to age, occupation, and
      education. The intercorrelations between the 3 scales in all 7 groups were
      significant and positive. A general high-loaded factor of death distress was
      extracted in all 7 groups. It was the only salient factor, accounting for 50-70%
      of the common variance.

PMID- 15493084
TI  - Cannabis and psychosis.

PMID- 15493085
TI  - Cannabis and psychosis.

PMID- 15493086
TI  - The unique needs of Medicare beneficiaries.

PMID- 15493087
TI  - Abstracts from a joint meeting of the Danish Society of Clinical Pharmacology and
      the Danish Society of Pharmacology and Toxicology. January 21, 2004, Odense,
      Denmark.

PMID- 15493088
TI  - Abstracts from the meeting of the Norwegian Society of Pharmacology and
      Toxicology. January 29-February 1, 2004, Beito, Norway.

PMID- 15493089
TI  - Special issue: HLA alleles and other immunogenetic polymorphism frequencies from
      world wide populations.

PMID- 15493090
TI  - Abstracts of the American Society for Histocompatibility and Immunogenetics 30th
      Annual Meeting. October 2-6, 2004, San Antonio, Texas, USA.

PMID- 15493091
TI  - Nonsurgical periodontal therapy.

PMID- 15493092
TI  - Comment on Lambert and Hartsough (1998).

PMID- 15493093
TI  - Speech perception deficits in poor readers: a reply to Denenberg's critique.
AB  - We reply to Denenberg's (1999) recent critique of our work (Mody, Studdert
      Kennedy, & Brady, 1997). Denenberg mounted two main lines of criticism, one
      concerning characteristics of the population sampled for the experimental group,
      and the other a statistical critique, concerning (a) violation of parametric
      assumptions for use of the F distribution and (b) our supposed acceptance of the
      null hypothesis of no differences between experimental and control groups. We
      show that the first criticism stemmed from a misunderstanding of the experimental
      hypothesis and that the second can be answered by both parametric and
      nonparametric comparisons across conditions within the experimental group,
      without reference to the control group. Thus, our original conclusion stands: The
      difficulty with rapid /ba/-/da/ discrimination that some children with reading
      impairment may experience does not stem from difficulty in discriminating the
      rapid spectral transitions at stop-vowel syllable onsets.

PMID- 15493094
TI  - Naming-speed processes and developmental reading disabilities: an introduction to
      the special issue on the double-deficit hypothesis.

PMID- 15493095
TI  - Naming speed, phonological awareness, and orthographic knowledge in second
      graders.
AB  - Concurrent relationships among measures of naming speed, phonological awareness,
      orthographic skill, and other reading subskills were explored in a representative
      sample of second graders. Hierarchical regression analyses revealed that naming
      speed, as measured by the the rapid automatized naming (RAN) task, accounted for
      a sizable amount of unique variance in reading with vocabulary and phonemic
      awareness partialled out. The unique contribution of naming speed to reading was
      relatively stronger for orthographic skills, whereas the contribution of phonemic
      skills was stronger for nonword decoding. In further analyses, marked
      difficulties on a range of reading tasks, including orthographic processing, were
      seen in a subgroup with a double deficit (slow naming speed and low phonemic
      awareness) but not in groups with only a single deficit. These findings are
      broadly consistent with Bowers and Wolf's (1993a, 1993b; Wolf & Bowers, 1999)
      double-deficit hypothesis of reading disability.

PMID- 15493096
TI  - Remediating the core deficits of developmental reading disability: a double
      deficit perspective.
AB  - The double-deficit hypothesis (Wolf, 1997; Wolf & Bowers, 1999, this issue)
      contends that deficits in phonological awareness and deficits in visual naming
      speed represent two independent causal impediments to reading acquisition for
      children with developmental reading disabilities (RD). One hundred and sixty-six
      children with severe RD from 7 to 13 years of age were classified into three
      deficit subgroups according to a double-deficit framework. A total of 140
      children with RD, 84% of the sample, were classified; 54% demonstrated a double
      deficit (DD), 22% a phonological deficit only (PHON), and 24% a visual-naming
      speed deficit only (VNS). Diagnostic test profiles highlighted the joint
      contributions of the two core deficits in depressing written language
      acquisition. The children in the DD group were more globally impaired than those
      in the other subgroups, and the VNS group children were the highest achieving and
      most selectively impaired readers. Following 35 hours of word identification
      training, sizable gains and significant generalization of training effects were
      achieved by all subgroups. A metacognitive phonics program resulted in greater
      generalized effects across the domain of real English words, and a phonological
      training program produced superior outcomes within the phonological processing
      domain. The greatest non-word reading gains were achieved by children with only
      phonological deficits.

PMID- 15493097
TI  - A clinical rationale for assessing rapid automatized naming in children with
      language disorders.
AB  - Three continuous rapid naming tasks (Semel, Wiig, & Secord, 1995) were
      administered to 2,450 American, English-speaking, academically achieving
      individuals with typical language development and intellectual ability (ages 6 to
      21 years) and 136 individuals with primary language disorders (LD; ages 6, 7, 9,
      11, 12, 15-16). Naming time in seconds differed significantly (p < .01) between
      the groups for color naming (Task 1) at age 12, shape naming (Task 2) at age 6,
      and color-shape naming (Task 3) at ages 6, 7, 9, and 12. Naming accuracy did not
      differ significantly (p > .01) between groups at the majority of the age levels
      compared. In the normative group, naming speed increased with age in a monotonic
      progression. The developmental trajectory in the LD group was essentially
      parallel, but elevated. The percentages of individuals who failed the naming-time
      criteria for Task 3 (color-shape naming) differed significantly in the two groups
      at all ages compared (p < .05). These findings indicate that the requirements for
      two-dimensional, continuous naming (Task 3 color-shape naming) resulted in
      reduced naming speed (longer total times) and interference with fluency in
      language production in about half of the clinical sample.

PMID- 15493098
TI  - Retrieval, automaticity, vocabulary elaboration, orthography (RAVE-O): a
      comprehensive, fluency-based reading intervention program.
AB  - The most important implication of the double-deficit hypothesis (Wolf & Bowers,
      in this issue) concerns a new emphasis on fluency and automaticity in
      intervention for children with developmental reading disabilities. The RAVE-O
      (Retrieval, Automaticity, Vocabulary Elaboration, Orthography) program is an
      experimental, fluency-based approach to reading intervention that is designed to
      accompany a phonological analysis program. In an effort to address multiple
      possible sources of dysfluency in readers with disabilities, the program involves
      comprehensive emphases both on fluency in word attack, word identification, and
      comprehension and on automaticity in underlying componential processes (e.g.,
      phonological, orthographic, semantic, and lexical retrieval skills). The goals,
      theoretical principles, and applied activities of the RAVE-O curriculum are
      described with particular stress on facilitating the development of rapid
      orthographic pattern recognition and on changing children's attitudes toward
      language.

PMID- 15493099
TI  - Naming-speed processes, timing, and reading: a conceptual review.
AB  - This article integrates the findings in the special issue with a comprehensive
      review of the evidence for seven central questions about the role of naming-speed
      deficits in developmental reading disabilities. Cross-sectional, longitudinal,
      and cross-linguistic research on naming-speed processes, timing processes, and
      reading is presented. An evolving model of visual naming illustrates areas of
      difference and areas of overlap between naming speed and phonology in their
      underlying requirements. Work in the cognitive neurosciences is used to explore
      two nonexclusive hypotheses about the putative links between naming speed and
      reading processes and about the sources of disruption that may cause subtypes of
      reading disabilities predicted by the double-deficit hypothesis. Finally, the
      implications of the work in this special issue for diagnosis and intervention are
      elaborated.

PMID- 15493100
TI  - Lean Management and Six-Sigma yield big gains in hospital's immediate response
      laboratory. Quality improvement techniques save more than $400,000.
AB  - DSI Laboratories has used Lean and Six-Sigma methodologies to systematically
      eliminate waste and reduce variation in its hospital clinical laboratory. The net
      result was a savings of more than $400,000 in the first year. After mapping its
      process, the laboratory found that phlebotomists were submitting samples in large
      batches, which created an early-morning flood of specimens. Switching to single
      piece workflow and distributing the workload more evenly allowed DSI to cover the
      same number of patients with two to three phlebotomists instead of 12. By
      establishing a more efficient workflow process within the laboratory, a single
      technologist could quickly move between stations and perform those tests that
      made up 80% of the work volume. New inventory management techniques reduced both
      excess inventory and the risk of shortages. Cost savings for the first year were:
      Reduced overtime spending by 60% ($78,000), Reassigned six phlebotomists for an
      annual savings of $160,000, 4.5 fewer technologist positions for a savings of
      $250,000.

PMID- 15493101
TI  - Building a high-retention culture in healthcare: fifteen ways to get good people
      to stay.

PMID- 15493102
TI  - Case study: improving efficiency in a large hospital laboratory.
AB  - Saint Francis Health System (SFHS) consists of three hospitals and one clinic:
      Saint Francis Hospital (SFH); Broken Arrow Medical Center; Laureate Psychiatric
      Hospital; and Warren Clinic. SFHS has 670 physicians on staff and serves medical
      (oncology, orthopedic, neurology, and renal), surgical, cardiac, women and
      infant, pediatric, transplant, and trauma patients in Tulsa County, Oklahoma,
      which has a population of 660,000. SFH incorporates 706 staffed beds, including
      126 pediatric beds and 119 critical care beds. Each year, the health system
      averages 38,000 admissions, 70,000 emergency department visits, 25,000 surgeries,
      and 3,500 births. Saint Francis Laboratory is located within the main hospital
      facility (SFH) and functions as a core lab for the health system. The lab also
      coordinates lab services with Saint Francis Heart Hospital, a physician-system
      joint venture. The Optimal Equipment Configuration (OEC) Project was designed by
      the Clinical Laboratory Services division of Premier, a group purchasing
      organization, with the goal of determining whether laboratories could improve
      efficiency and decrease unit cost by using a single-source vendor. Participants
      included seven business partners (Abbott, Bayer, Beckman/Coulter, Dade/Behring,
      J&J/ Ortho, Olympus, and Roche) and 21 laboratory sites (a small, mid-sized, and
      large site for each vendor). SFH laboratory staff embraced Premier's concept and
      viewed the OEC project as an opportunity to "energize" laboratory operations. SFH
      partnered with Abbott, their primary equipment vendor, for the project. Using
      resources and tools made available through the project, the laboratory was re
      engineered to simplify workflow, increase productivity, and decrease costs by
      adding automation and changing to centralized specimen processing. Abbott and SFH
      shared a common vision for the project and enhanced their partnership through
      increased communication and problem solving. Abbott's area representatives
      provided for third-party design expertise and quarterly metric reporting through
      Argent Consulting. Abbott incorporated lessons learned from the SFH OEC project
      with organizational changes to improve the way they work with customers.
      Following is a step-by-step description of the OEC project to allow others to
      benefit from the experience (Figure 1).

PMID- 15493103
TI  - Don't waste my time! A guide to common sense meetings.
AB  - "The significant problems we face today cannot be solved at the same level of
      thinking we were at when we created them." --Albert Einstein Woody Allen once
      said we live in a world with "too many moving parts." Health care is a prime
      example of this level of complexity. To meet the challenges of change, the
      ability of leaders to work constructively with each other is essential. This
      requires team effort, extracting from a variety of venues, incorporating diverse
      experts, and effective use of available resources. To achieve this, a well
      functioning committee process is generally required. Examination of this process
      and noting various employable techniques is useful in order to effectively
      respond to the constant changes in health care and how they apply to the
      laboratory environment. It is a well-established fact that committee meetings can
      be a waste of time if not properly prepared for or perceived by committee members
      or others to be poorly managed. Committee participants quickly recognize this and
      can be less than cooperative, resulting in failing to meet the desired goals for
      that committee. The intent of this article is to provide some common sense
      activities that can contribute to managing a meeting in a productive and timely
      manner.

PMID- 15493104
TI  - Points for consideration: transferring and changing hospital clinical
      laboratories.
AB  - BACKGROUND: The laboratories of Carmel Medical Centre were located in the main
      hospital building since its establishment (1977). Due to expansion of the
      clinical wards, the laboratories were relocated to a nearby building. The project
      was utilized for reorganization of the laboratories. METHODS: The basic design
      addressed the existing hospital needs based mainly on the original organization
      of the laboratories. The project allowed for the prospective organizational
      changes. The planning, design, and erection were performed by teams of the
      hospital and by outside parties, headed by the hospital management and the
      laboratories' director. The laboratories' staff was involved in all phases of the
      project. RESULTS: The project laid the foundations for future consolidation,
      i.e., establishment of a central reception station and merging of chemistry,
      endocrinology, pharmacology, and segments of immunology. The merging involved
      performance but not validation of tests. Separation between research and routine
      work was achieved. By-products attained were as follows: simplification of tube
      handling, reduction in volume of blood needed, improvements in safety, employees'
      amenities, general atmosphere, and communication within personnel. CONCLUSION:
      The successful transfer resulted from appropriate design, close cooperation
      between management and personnel, and the ability to pinpoint problems at early
      stages with ad hoc solutions.

PMID- 15493105
TI  - Management by surprises.

PMID- 15493106
TI  - Reporting lab results directly to the patient.

PMID- 15493107
TI  - Common cents 20: beta & better.

PMID- 15493108
TI  - Renovation part 1: assessing the damage.
AB  - Once a general analysis of existing conditions is complete, a clearer picture of
      renovation costs and feasibility should emerge. This may be a point of
      renegotiation with owners. If the assigned space proves unsuitable in layout or
      requires budget busting upgrades to utilities, you may, now equipped with the
      results of your fact finding developed in concert with third party professionals,
      revisit the subjects of location and budget with owners. If, on the other hand,
      your survey reveals that you have indeed discovered a good foundation for
      renovation that fits the budget, it's time to swallow that lump in your throat
      and proceed.

PMID- 15493109
TI  - Managing outreach programs: stories from the front lines.

PMID- 15493110
TI  - Quality in the clinical laboratory--the paradigm shift has arrived.
AB  - Whether we practice laboratory medicine in a physician office laboratory or a
      university hospital laboratory, we find ourselves in the midst of the new focus
      on total quality, that of quality management of systems. For many decades,
      manufacturing has placed an emphasis on not just quality control of a process but
      quality as an expected outcome of their system. Now is the time for laboratory
      professionals to focus on the future by beginning to develop systems thinking and
      pursue quality as an outcome. We may not realize it, but we are in the midst of a
      shift in our Paradigm of Quality. In his book, From Quality to Business
      Excellence, Charles G. Cobb, states: "The organization, like the human body, is a
      system; to make it healthy you must consider the whole as well as the parts. That
      requires looking at the 'system' from a broad cross-functional perspective, just
      as in a medical analogy, a general practitioner provides an overall view and
      integrates a team of other specialists as needed".

PMID- 15493111
TI  - [Expectation and development of atypical antipsychotic drugs].

PMID- 15493112
TI  - [Physiology and biochemistry of uric acid].
AB  - In humans, uric acid is the final breakdown product of unwanted purine
      nucleotides. Uric acid is the last stage in purine degradation, because humans
      lack the enzyme uricase which converts uric acid into allantoin. Uric acid has
      profound beneficial effects since it scavenges potential harmful radicals in our
      body. However, in conjunction with genetic or environmental factors, uric acid
      can cause significant health problems, leading to kidney stones when it builds up
      in the kidneys and to gout when crystals accumulate in the joints. The levels of
      uric acid in the blood must be tightly controlled to minimize these detrimental
      effects. Normally, the body eliminates enough uric acid in the kidney, and in
      part also through the intestines, to keep its concentration at a healthy level in
      the blood (approximately 300 microM). In patients with gout or kidney stone
      disease, however, the body either produces excessive amounts of uric acid or its
      ability to eliminate uric acid is disturbed in some way. In the kidney, uric acid
      is reabsorbed via the uric acid transporter URAT1. This transporter is the major
      mechanism for regulating blood uric acid levels and therefore may prove an
      interesting target for future drug development.

PMID- 15493113
TI  - [Serum uric acid--a cardiovasular risk factor?].
AB  - Serum uric acid represents an important, independent risk factor for
      cardiovascular and renal disease in patients with hypertension, heart failure, or
      diabetes. Elevated serum uric acid is highly predictive of mortality in patients
      with heart failure or coronary artery disease and of cardiovascular events in
      patients with diabetes. Although the mechanism(s) by which uric acid may play a
      pathogenetic role in cardiovascular disease is unclear, hyperuricemia is
      associated with deleterious effects on endothelial dysfunction, oxidative
      metabolism, platelet adhesiveness, hemrheology, and aggregation. Whether a
      reduction in uric acid impacts CV and renal disease remains to be determined.
      However, recent findings from LIFE in hypertensive patients with LVH suggest the
      possibility that a treatment-induced decrease in serum uric acid may indeed
      attenuate cardiovascular risk. Almost one third of the treatment benefit of a
      losartan-based versus atenolol-based therapy on the composite endpoint (death,
      myocardial infarction, or stroke) may be ascribed to differences in achieved
      serum uric acid levels. Clearly, randomized clinical trials are needed to
      investigate further the long-term cardioprotective benefits issue of reducing
      hyperuricemia in hypertensive patients.

PMID- 15493114
TI  - [Uric acid and multiple sclerosis].
AB  - Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous
      system. Its etiology is not known, but it is well established that auto-reactive
      T-cells and monocytes play an important pathogenetic role. Experimental allergic
      encephalomyelitis (EAE) of mice serves as disease model for MS. In both EAE and
      MS inflammatory cells produce nitric oxide and its oxidizing congeners such as
      peroxynitrite. Peroxynitrite and other reactive nitrogen oxide species exert a
      toxic effect on neurons, axons and glia cells and enhance apoptosis. In addition,
      they increase the blood-CNS-barrier permeability and can therefore promote
      invasion of inflammatory cells into the CNS. On the other hand, uric acid, a
      peroxynitrite scavenger inhibits blood-CNS-barrier permeability changes, CNS
      inflammation and tissue damage in EAE. Epidemiological studies have shown that MS
      and gout are almost mutually exclusive diseases. Uric acid levels in MS patients
      are lower than in controls and in patients with active disease lower than in MS
      patients in remission. Inosine, a uric acid precursor, can be used to raise uric
      acid levels in serum and may provide some benefit in MS patients. A small study
      of ten patients with progressive MS has demonstrated some improved function in
      three of them and no sign of progression or relapse in the other. However, this
      study does not justify a recommendation for use of inosine in MS patients yet. At
      present, uric acid can solely be regarded as a marker of disease activity in MS.
      In addition, the current knowledge of uric acid and MS supports hypotheses which
      predict a positive effect of radical scavengers in MS.

PMID- 15493115
TI  - [Uric acid, a neglected molecule--the value of imaging].
AB  - Imaging plays a key role in two longterm effects of hyperuricemia: those on the
      urinary tract and on the skeletal system. This overview concentrates on the
      diagnosis of urinary stones and of musculoskeletal gout. Urinary stones are
      negative on radiography, i.e., they cannot be differentiated from the surrounding
      tissues, and even at intravenous urography only non specific filling defects are
      shown that may be hard to differentiate from blood clots and papillary necrosis
      whereas computed tomography without a contrast agent is highly sensitive in
      detecting all types of stones whether negative or positive at radiography. Gout
      of the musculoskeletal system usually manifests as an acute gouty arthritis after
      a long-standing asymptomatic hyperuricemia. An intercritical phase may follow
      before new acute attacks and--in up to 50%--chronic gout develop. During acute
      gouty arthritis imaging is non-specific. The distribution pattern, the relation
      of soft tissue changes and osteolytic paraarticular changes, calcifications and
      the lack of osteoporosis are a typical, nearly pathognomonic constellation of
      chronic tophaceous gout. In selected cases CT or MRI may add critical local
      information.

PMID- 15493116
TI  - [Gout and its differential diagnosis].
AB  - Arthritis urica is one of the most frequent forms of arthritis in Switzerland. On
      one hand it can mimic septic arthritis, on the other hand it may progress into
      chronic polyarticular disease. Age, sex and initial clinical presentation lead to
      the suspicion of crystal arthropathy. The diagnosis, however, has to be proven by
      microscopic analysis of synovial fluid. Functional ultrasound may be extremely
      helpful in collecting minute amounts of liquid in small joints. This approach
      enables definite diagnosis and at the same time crystalline glucocorticoids
      together with local anesthetics can be injected intra-articularly in order to
      interrupt the inflammatory process and to kill pain. Other conventional treatment
      modalities include non-steroidal anti-inflammatory drugs (including Cox-2
      inhibitors) which should be started immediately and at maximal doses as well as
      glucocorticoids at moderate doses for a few days. Serum uric acid levels should
      be normalized in order to prevent recurrence of arthritis.

PMID- 15493117
TI  - [Gout nephropathy--ghost or reality?].
AB  - Until the past decades, end stage renal disease was considered a major cause of
      death among patients with gout. Modern long-term follow up studies of renal
      function however have indicated that hyperuricemia and gout rarely result in
      kidney damage unless other renal diseases supervene. Subsequently, the use of the
      EDTA lead mobilization test confirmed that gout in the presence of chronic renal
      failure is a useful marker of chronic lead intoxication. Chelation treatment with
      EDTA can slow the progression of renal insufficiency, without apparent damage
      associated with the use of the chelating agent. Since chronic lead intoxication
      may remain clinically concealed for years, a high index of suspicion is
      warranted. Occult lead intoxication should be sought actively in gouty patients
      with chronic renal insufficiency of unknown etiology.

PMID- 15493118
TI  - [Diagnosis and prevention of uric acid stones].
AB  - Uric acid stones occur in 10% of all kidney stones and are the second most-common
      cause of urinary stones after calcium oxalate and calcium phosphate calculi. The
      most important risk factor for uric acid crystallization and stone formation is a
      low urine pH (below 5.5) rather than an increased urinary uric acid excretion.
      Main causes of low urine pH are tubular disorders (including gout), chronic
      diarrhea or severe dehydration. Uric acid stone disease can be prevented and
      these are one of the few urinary tract stones that can be dissolved successfully.
      The treatment of uric acid stones consists not only of hydration (urine volume
      above 2000 ml daily), but mainly of urine alkalinization to pH values between 6.2
      and 6.8. Urinary alkalization with potassium citrate or sodium bicarbonate is a
      highly effective treatment, resulting in dissolution of existing stones. Urinary
      uric acid excretion can be reduced by a low-purine diet. Potassium citrate is the
      treatment of choice for the prevention of recurrence of uric acid calculi.
      Allopurinol reduces the frequency of stone formation in hyperuricosuric patients
      with recurrent uric acid stones and/or gout.

PMID- 15493119
TI  - [Life-threatening adverse effects of pharmacologic antihyperuricemic therapy].
AB  - Minor hypersensitivity reactions to allopurinol presenting as skin rash occur in
      approximately 2% of patients. A more severe, albeit rare, hypersensitivity
      reaction with fever, eosinophilia, dermatitis, renal failure, vasculitis and
      hepatic dysfunction carries a mortality of up to 20%. The incidence of this
      severe reaction can probably be reduced by adjusting the dose of allopurinol in
      patients with impaired renal function. Azathioprine and mercaptopurine are
      metabolised by xanthine oxidase, the enzyme that is inhibited by allopurinol.
      Concomitant administration can result in life-threatening neutropenia unless the
      dose of allopurinol is reduced by approximately 75%. The uricosuric agent
      benzbromarone has recently been withdrawn from the market because of several
      cases of fulminant hepatic failure with subsequent death of the patient or liver
      transplantation.

PMID- 15493120
TI  - [Rasburicase (Fasturtec)].
AB  - Rasburicase (Fasturtec) is an enzyme that transforms uric acid to the more water
      soluble allantoin to be excreted by the kidneys. Rasburicase fulfills an unmet
      clinical need in the treatment of hyperuricemia in that it produces a more rapid
      action of controlling serum uric acid compared with allopurinol. Tumours with
      high proliferative rate and sensitive to chemotherapy such as hematological
      malignancies (mainly) solid tumours (occasionally) may lead to a tumor lysis
      syndrome. In this situation rasburicase can effectively lower serum uric acid
      concentrations with a secondary improvement in renal function. Hyperuricemia is
      the hallmark of severe gout with tophi formation. Rasburicase represents an
      interesting new option in controlling serum uric acid in patients with severe
      tophaceous gout.

PMID- 15493121
TI  - [Serum concentration of uric acid, a diagnostic 'must' in patients with
      hyponatremia].
AB  - The renal handling of urate involves complete glomerular filtration followed by
      reabsorption and secretion mainly in the proximal renal tubule. The amount of
      urate excreted depends on the extracellular fluid volume. Expansion of
      extracellular fluid volume increases and contraction of extracellular fluid
      volume decreases the clearance of urate. In the syndrome of inappropriate
      secretion of antidiuretic hormone, there is volume expansion associated with low
      uric acid. A comparable situation is observed whenever exaggerated amounts of
      free water are consumed. Similarly, hypouricaemia and a tendency to low serum
      sodium concentrations are observed in normal pregnancy, a state with volume
      expansion, a physiological situation reversed when eclampsia occurs. On the other
      hand, when hyponatraemia is associated with contraction of extracellular fluid
      volume as it is often the case when thiazides or loop-diuretics are administered,
      hyponatraemia is paralleled by increased serum uric acid concentrations.

PMID- 15493122
TI  - [Nutritional health aspects of mycotoxins].
AB  - Mycotoxins produced by mould fungi can enter into the human food chain directly
      through foods of plant origin (cereal grains), consumer goods (coffee and bear)
      and indirectly through foods of animal origin (kidney, liver, milk and eggs).
      Mycotoxins occur in small amount in the foods; however their continuous intake
      even in microdoses can result in accumulation in the organism. Synergic effects
      of the mycotoxins as well as their possible additive multi-toxic effects seem to
      be especially dangerous. Mycotoxin problems are very important in Hungary because
      these natural toxins occur mainly in those cereals (e.g. wheat, maize) that
      amount to high proportion of the sowing area in Hungary and provide the main
      foods to the inhabitants. Public health risks of the toxins accumulating in the
      human and animal bodies during the long term consumption of the mycotoxins
      containing foods--even in small doses--have not been evaluated yet as thoroughly
      as their importance would require. However, there are more and more direct and
      indirect expressions of the danger resulting from the toxins. The most frequently
      observed human health effects are carcinogen effects (aflatoxin, ochratoxin A,
      fumonisins, patulin); effects causing developmental abnormalities (zearalenon,
      ochratoxin); effects harmful to the reproduction (zearalenon, and trichotecenes),
      effects decreasing the resistance; immunosuppressive effects (trichotecenes), and
      effects causing injury of the nervous system (ochratoxin A, fumonisins).
      Prevention of the injury of the health caused by mycotoxins can be completed by
      joint and integrated activity of the various disciplines only and requires a
      comprehensive interdisciplinary cooperation. This paper gives a discussion on
      health injuring effects of the most frequently occurring mycotoxins that are very
      important from human health aspects in Hungary; on their occurrence in the foods
      and on their human risk.

PMID- 15493123
TI  - [Update treatment of hepatic encephalopathy].
AB  - According to morbidity data in Hungary, the number of death caused by liver
      diseases is still high. Liver diseases come 6th on the morbidity statistics.
      Nowadays, the living standards of patients appropriately treated are higher,
      these patients have longer living perspectives. Author aims at summarizing the
      treatment options of hepatic encephalopathy in cases of subclinical, acute and
      chronic forms of chronic liver diseases as well as in case of fulminant form of
      acute liver disorder.

PMID- 15493124
TI  - [Market share of the for-profit and not-for-profit sector from health insurance
      expenditures].
AB  - AIM: The aim of the study is to analyze the market share of for-profit private
      and not-for-profit sector from the expenditures on medical services of the
      Hungarian National Health Insurance Fund (NHIF), to show its changes in the last
      years and to show on which field they can be found. DATA AND METHODS: The data
      derives from the financial database of the National Health Insurance Fund (NHIF)
      covering the period 1995-2002. The analysis includes the medical provisions
      (primary care, health visitors, dental care, out- and inpatient care, home care,
      kidney dialysis, CT-MRI). RESULTS: In 1995 only 6.91% (12.5 billions Ft) of total
      expenditure for medical services went to for-profit private providers. By 2002
      the market share of private providers increased to 15.95% (78.5 billions Ft).
      During the same period we realized a dynamic increase in the market share of non
      profit sector: from 1.04% in 1995 to 2.58% in 2002. The role of private providers
      is dominant in the case of general practitioners, dental care, transportation,
      kidney dialysis, CT/MRI and home care (home nursing). CONCLUSIONS: The financial
      data of the NHIF showed the dynamic increase of market share of for-profit
      private providers and non-profit sector in many field of health care, although
      they role in the two most important fields (out- and inpatient care) is still
      negligible.

PMID- 15493125
TI  - [Neuropeptide containing nerve fibres in the liver].
AB  - INTRODUCTION: A large number of neuropeptide/neurotransmitter containing nerve
      fibres were observed in the whole gastrointestinal tract, so in the liver and it
      is supposed they might play a very important role in the microcirculation and the
      functions of the hepatocytes. AIM: The distribution, density, the close
      relationship to the effector cells, as well as the origin of the different
      neuropeptide containing nerve fibres were investigated by the aid of immunohisto-
      and immunocytochemistry. The obtained data were compared to the results gained
      with TH, DBH and NOS antisera. RESULTS: Large number of the neuropeptide IR nerve
      fibres were observed mainly around the portal triad, especially around the
      interlobular a. and v., however, some IR nerve fibres were observed
      intralobullary, too. With the aid of EM the synaptic space is 20-200 nm between
      the IR nerve fibres and the effector cells. The greatest density of the IR nerve
      fibres were found NPY, TH and DBH IR, mainly around the arteries, however, some
      NPY, SP, SOM IR nerve fibres were observed in the space of Disse. VIP, NOS, CGRP
      IR nerve fibres were found only very rarely, they were located around the portal
      triad. Some intramural ganglia were also observed in the porta hepatis and in the
      main intralobular septum, where SOM, VIP and NPY IR multipolar nerve cell bodies
      were found. After the extrinsic denervation all of the CGRP ans SP IR nerve
      fibres disappeared in the liver and the number of the TH, DBH and NPY IR nerve
      fibers were also decreased. CONCLUSIONS: On the basis of these morphological
      data, it is supposed that these neuropeptide containing nerve fibres might play a
      very important role in the control of the blood flow, in the function of the
      hepatocytes, so the metabolism of the glucose, lipids, the production of the
      bile, and so on.

PMID- 15493126
TI  - [Treatment of obesity].

PMID- 15493127
TI  - [The beginnings and evolution of clinical electrocardiology].

PMID- 15493128
TI  - [Pal Schwarczmann (1904-1980)].

PMID- 15493129
TI  - [Growth behaviour of human mononuclear cells derived from bone marrow and cord
      blood on a collagen carrier for osteogenic regeneration].
AB  - We investigated the biocompatibility and osteogenetic potency of a porcine
      collagen I/III carrier in a human bone marrow and cord blood cell culture system.
      METHODS: Human mesenchymal mononuclear cells were isolated from cord blood and
      iliac crest bone marrow and cultivated in various cell densities on a
      semipermeable porcine collagen I/III carrier. After 14 days of in vitro
      cultivation both cultures were subjected to osteogenic stimulation by
      dexamethasone, ascorbic acid and beta-glycerol phosphate (DAG) until day 40.
      Semiquantitative immunochemical evaluation based on osteoblastic and progenitor
      cell markers was then done. RESULTS: With regard to the minimal local cell
      density required for growth and osteogenic differentiation, cord blood derived
      progenitor cells showed lower tolerance in comparison with bone marrow derived
      cells. For both cell culture systems three-dimensional growth and calcification
      within the collagen fibres were seen after osteogenic stimulation. CONCLUSION:
      Human cord blood and bone marrow derived mesenchymal stem cell are capable of
      differentiating into osteoblasts after incubation with a collagen I/III
      biomaterial.

PMID- 15493130
TI  - [A multichannel device for the noninvasive analysis of the state and function of
      organs and tissues].
AB  - The subject of this paper is to present a technical description of a high
      performance, modular research device, designed and constructed with the aim of
      enabling the non-invasive investigation of the passive electrical properties of
      biological tissue in the frequency range 1 kHz-1 MHz. The modular hardware- and
      software of the device makes the system highly flexible when it comes to applying
      a wide range of methods for the non-invasive analysis of the state and function
      of biological tissues and evaluating them in a clinical setting. Furthermore, the
      concept also makes it possible to combine the modules in new ways for new
      applications, to accommodate future developments in bio-impedance research.

PMID- 15493131
TI  - [Phenomenological statistics of laser irradiation related metabolic changes in
      guinea pig livers].
AB  - In the past, dosimetric investigations on which hyperthermal therapy radiation
      planning for minimally invasive treatment of tumours were based were often
      limited to tissue coagulation. While heatshock proteins identified by biochemical
      basic research provided a fundamental knowledge of the thermal processes of
      tissue reactions between 42 degrees C and ca. 45 degrees C, the resulting
      understanding was insufficient to serve as a basis for radiation planning. For
      this reason, the Arrhenius formalism has so far been used as a good approximation
      for the complex description of the hyperthermal tissue reactions, with the
      activation energy being employed as statistic energy threshold for irreversible
      tissue coagulation. Our investigations were aimed at elucidating whether this
      formalism could be kept reproducible for tissue damage as temporal accumulation
      with an implicit biochemically balanced feedback mechanism, i.e. below the
      coagulation threshold. In our experiments we chose the fluorescence-technical
      measurement of the NADH concentration as a vital parameter to obtain a more
      informative statement in a preliminary phenomenological approach. The two most
      striking differences--as compared with the vitality measurement from the
      Arrhenius formalism--are the negligible variations in the damage integral (as
      compared with the phenomenological metabolic reactions acquired by cyclic
      heating), and the conclusion that the Arrhenius formalism as quasi-linear
      correlation between metabolic dynamics and tissue damage, will not hold.

PMID- 15493132
TI  - [Electrospun poly-l-lactide nanofibres as scaffolds for tissue engineering].
AB  - Tissue engineering is a promising tool for treating structural and functional
      defects in bone and cartilage. To provide optimal conditions for three
      dimensional cell growth the use of a scaffold is necessary. The aim of the study
      was to test the potential application of an electrospun poly (l-lactide)
      nanostructured scaffold as a matrix for tissue engineering. Matrices were seeded
      with human osteosarcoma MG-63 cells and cultivated for 14 days. Cells showed a
      clear preference for growth along the nanofibres, and demonstrated no signs of
      degeneration or apoptosis. The fine structure of electrospun nanofibres makes
      them an ideal scaffold for tissue engineering, in particular for cartilage
      repair. They can be "doped" with growth factors, medications, etc., and are both
      biocompatible and biodegradable.

PMID- 15493133
TI  - [Tractive force measurement in bone transport--an in vivo investigation in
      humans].
AB  - Bone transport applying the principle of distraction osteogenesis makes it
      possible to reconstruct long bone defects caused by trauma or resection of bone
      tumors. The method employing a central cable, developed in Munich, is especially
      suitable for such applications. The main bone fragments are stabilized by an
      external fixateur, and bone transport is effected with a single central cable
      fixed to the tip of the segment, and driven by an external, programmable motor.
      In 15 patients the tractive forces during the entire bone transport were measured
      with a strain gauge incorporated within the cable. On the basis of the force
      profiles characteristics normal bone transport (forces between 150-250 N) can be
      distinguished from a critical transport (forces > 250 N) with the risk of
      premature consolidation. There is some evidence that at a very high level of
      force, just before premature consolidation a very effective form of bone
      transport with good bone neoformation can be achieved. Transport systems
      employing a central cable allow this special form of distraction osteogenesis,
      since there is continuous force monitoring, and there is the option of employing
      the traction force as a control factor in a loop.

PMID- 15493134
TI  - [Accuracy of an image-free cup navigation system--an anatomical study].
AB  - The position of the acetabular cup is of decisive importance for the function of
      a total hip replacement (THR). Using the conventional surgical technique, correct
      placement of the cup often fails due to a lack of information about pelvic tilt.
      With CT-based and fluoroscopically-assisted navigation procedures the accuracy of
      implantation has been significantly improved. However, additional radiation
      exposure, high cost and the increased time requirement have hampered the
      acceptance of these techniques. The present anatomical study evaluates the
      accuracy of an alternative procedure--image-free navigation. This method requires
      little extra effort, does not substantially delay surgery, and needs no
      additional imaging. Press-fit cups were implanted in 10 human cadaveric hips with
      the help of the image-free navigation system, and the position of the cups was
      checked intraoperatively with a CT-based navigation system and postoperatively by
      computed tomography. All cups were implanted within the targeted safe zone with
      an average inclination of 44 degrees (range 40 degrees-48 degrees, SABW 2.7
      degrees) and an average anteversion of 18 degrees (range 12-24 degrees, SABW 4.1
      degrees). Analysis of accuracy of the image-free navigation software revealed
      only a small, clinically tolerable deviation in cup anteversion and cup
      inclination in comparison with the CT-based navigation system and the post
      operative CT scans. The evaluated image-free navigation system appears to be a
      practicable and reliable alternative to the computer-assisted implantation of
      acetabular cups in total hip arthroplasty.

PMID- 15493135
TI  - The tRNA and rRNA genes in the Oryza sativa genome.
AB  - In the recently assembled genomes of rice Oryza sativa ssp. indica and japonica,
      we identified 564 and 519 tRNA genes, respectively. The modified wobble
      hypothesis, namely, at least 46 tRNA species must present in order to decode all
      61 possible anticodons, is perfectly observed in both subspecies. Among the 46
      tRNA species, indica and japonica have many identical ones in sequence. There are
      18 rice tRNA species that have identical counterparts in Arabidopsis. In the
      indica superscaffold dataset, 384 5S rRNA genes, dozens of 17S and 5.8S rRNA
      genes and one 25S rRNA gene were discovered. The incompleteness of observed rRNA
      genes is mainly caused by the fact that the rRNA genes always exist as tandem
      arrays in heterochromatic regions that are not successfully sequenced in a whole
      genome shotgun approach.

PMID- 15493136
TI  - [Purification and cloning of an antifungal protein from the rice diseases
      controlling bacterial strain Paenibacillus polymyxa WY110].
AB  - Paenibacillus polymyxa WY110, a plant growth-promoting bacteria strain isolated
      from rice rhizosphere could suppress the growth of various plant pathogens
      effectively. With (NH4)2SO4 fractional precipitation, DEAE-Sephadex A-50
      chromatography and Sephacryl S-200 chromatography followed by tracks of fraction
      antagonistic assay and SDS-PAGE, an antifungal protein P2 with in vitro anti
      Pyricularia oxyzae activity was isolated and purified. It was showed with
      antagonistic activity on PDA plates that the growth of Pyricularia oryzae was
      inhibited by 1.5 microg of P2 protein effectively. N-terminal amino acid residues
      analysis showed 24 amino acid sequence: H2N-Ala-Asn-Val-Phe-Trp-Glu-Pro-Leu-Ser
      Tyr-Tyr-Asn-Pro-Ser-Thr-Trp-Gln-Lys-Ala-Asp-Gly-Tyr-Ser-Asn-. Using this amino
      acid sequence as a target, the similarity of P2 protein was searched with BlastP
      program on Internet. It was showed a high homology between the P2 protein and the
      precursors of beta-1, 3-1, 4-glucanases from Bacillus. The beta-1, 3-1, 4
      glucanase activity of P2 protein was identified with the specific substrate
      lichenan. According to the N-terminal partial sequence of P2 protein and the C
      terminal conserved sequence of beta-1, 3-1, 4-glucanase, the primers for both
      terminals were synthesized. Using the genomic DNA of WY110 as the template, the
      full-length sequence of the gene encoding P2 was amplified by high fidelity PCR,
      then cloned into pMD18-T vecter. Sequence analysis showed the 72 nucleotide
      sequence on 5'-end matched with the known 24 amino acid sequence on N-terminal of
      P2 protein. The sequence (GenBank Accession Number: AF284449) was 636 bp in
      length encoding 212 amino acids. Comparing with a beta-1, 3-1, 4-glucanase gene
      (gluB) from Paenibacillus polymyxa, the sequence homology for nucleotides and
      deduced amino acids were 84% and 88.7% respectively. The cloning of the gene
      encoding P2 protein would be a new potential objective gene for plant gene
      engineering.

PMID- 15493137
TI  - [Assesment of genetic diversity of allelopathic rice germplasm based on RAPD and
      ISSR].
AB  - Random Amplified Polymorphic DNA (RAPD) and Inter-simple Sequence Repeat (ISSR)
      methods were used to detect the genetic diversity of 57 allelopathic rice
      accessions which were introduced from 10 countries or areas. A total of 12 RAPD
      primers and seven ISSR primers were indentified with polymorphism among the
      entries. For RAPD markers, 85 polymorphic bands were produced, percentage of
      polymorphic bands (PPB) were 69.4%. For ISSR marker, 34 polymorphic bands were
      generated, PPB were 53.0%. The result from the clustering analysis by UPGMA
      indicated that those accessions from the same geographical location were
      clustered into one group. It was also found that some rice accessions with higher
      allelopathic potential were clustered together, implying that the genes
      conferring allelopathy in those rice accessions might be isolocus. However, some
      rice accessions with different allelopathic potential clustered into the same
      group performed lower level of generic polymorphism which was attributed to
      oriented selection for other traits in breeding program. The estimates of
      correlation coefficient of RAPD and ISSR based on the genetic similarity matrices
      were significantly correlated.

PMID- 15493138
TI  - Cloning, sequence and expression analysis of a zinc finger protein gene in wheat.
AB  - Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was performed on total
      RNA of resistant-line TAM104R and susceptible-line TAM104S using 33 primers
      designed according to conservative domain of plant R-genes and the sequence of
      barley powdery mildew resistance genes Mlo, Mla1, Mla6 and wheat leaf rust
      resistance gene Lrk10. A polymorphic cDNA fragment TaZF was cloned and sequenced.
      The Open Reading Frame (ORF) of TaZF is comprised of 822 base pairs which encodes
      a zinc finger-like DNA or RNA-binding protein with 273 amino acids and molecular
      weight of 31 kD. TaZF is more than one copy gene in TAM104R genome based on
      southern blot. It is constitutively expressed, but level of expression was
      enhanced in tissue infected by Erysiphe Graminis. There is no intron in TaZF
      genome DNA.

PMID- 15493139
TI  - [The confirmation of putative natural hybrid species Meconopsis x cookei G.
      Taylor (Papaveraceae) based on nuclear ribosomal DNA ITS region sequence].
AB  - The Nuclear Ribosomal DNA internal transcribed spacers (ITS) region sequences
      from a putative natural hybrid species Meconopsis x cookei and its possible
      parents M. punicea and M. quintuplinervia were obtained by using direct
      sequencing method. The sequence length of ITS region (including ITS1, 5.8S and
      ITS2) is 667 bp for M. punicea, 668 bp for M. x cookei, and 668 bp for M.
      quintuplinervia. The sequences were aligned by the software Clustal X, and the
      bases per locus were compared by using software with manual method. The aligned
      sequence length is 688 bp, of which ITS1 is 254 bp, 5.8S is 162 bp, and ITS2 is
      252 bp. 16 variable loci were detected from the aligned sequence, approximately
      2.40% to the whole sequence length, of which ITS1 has nine variable loci
      (56.25%), ITS2 has six variable loci (37.50%), and 5.8S has one variable locus
      (6.25%). The results show that M. x cookei have two kinds of ITS sequences
      contributed from two species M. puniceaa and M. quintuplinervia, i.e. the
      variation of ITS gene among M. x cookei, M. punicea and M. quintuplinervia is
      congruence with the Mendel's genetics law. Therefore, the molecular evidences
      indicate that M. x cookei is a hybrid origin from M. punicea and M.
      quintuplinervia.

PMID- 15493140
TI  - [Cloning and characterization of two MADS box genes from peach (Prunus persica)].
AB  - With the aim of finding genes involved in the floral transition of Prunus species
      (Prunus sp.), the EST (expressed sequence tags) sequences were extracted from the
      public databases. Eight MADS box genes' cDNAs were obtained. Two of them, PpMADS4
      and PpMADS6 (The accession numbers in GenBank are AY705972 and AY705973), were
      cloned from peach (Prunus persica). The full length cDNA of PpMADS4 is 850 bp
      long. It contains an open reading frame of 732 bp, coding for a polypeptide of
      243 amino acids. The full length cDNA of PpMADS6 is 1,190 bp long. It contains an
      open reading frame of 768 bp coding for a polypeptide of 256 amino acids. PpMADS4
      closely resembles the Arabidopsis AGAMOUS gene. It is an AGAMOUS-like C class
      MADS box gene, and it expresses in petal, carpel, fruit and nutlet as
      demonstrated by RT-PCR analysis. PpMADS6 is likely to be the peach orthologue of
      the Petunia PFG genes and it is an A class MADS box gene. It has been shown with
      RT-PCR that it expresses in leaf, sepal, petal, carpel and fruit. It may be
      involved in the transition from the juvenile to the adult stage.

PMID- 15493141
TI  - Screening of a RAPD marker tightly linked to Co gene in apple and the SCAR marker
      conversion.
AB  - A DNA marker linked to the columnar gene (Co) in apple (Malus domestica) was
      explored based on the population of 105 progenies of 'Spur Fuji' x 'Telamon' by
      bulk segregant analysis (BSA) and Random Amplified Polymorphic DNA (RAPD)
      technique. A total of 300 random primers were screened and a RAPD marker
      (S1142(682)) closely linked to Co gene (2.86 cM) was identified and then
      sequenced. Four specific PCR primers (two forward primers and two reverse
      primers) were designed,and the products of SCAR-PCR indicated that all the four
      pairs of primers could amplify polymorphic bands between columnar and non
      columnar traits, so any of them could serve as the specific SCAR primers. One
      pair of these specific primers was chosen to amplify each individual in the
      population, and the result showed that the co-segregation pattern of this SCAR
      marker and Co gene was the same as that of the RAPD marker. Furthermore, it was
      found that the nucleotide sequence of the RAPD marker fragment contained an open
      reading frame (ORF) that could encode 68 deduced amino acid residues at the
      position of +45 - +251.

PMID- 15493142
TI  - [Study on gene expression of Tamarix under NaHCO3 stress using SSH technology].
AB  - The gene expression of Tamarix androssowii under NaHCO3 stresses is studied by
      using SSH technique, in which the cDNA from the materials treated with NaHCO3
      solution is as tester and the cDNA from the materials in normal growth is as
      driver. Total 36 genes related to NaHCO3 stress were obtained through Northern
      hybridization. Blastx analysis showed that the proteins encoded by these genes
      were homologous to the following proteins: the antioxidant enzymes catalase and
      peroxiredoxin; trehalose phosphatase, which was related to trehalose synthesis; a
      few regulation proteins such as bZIP transcription factor, MADS-box protein,
      glycine-rich RNA-binding proteins, CCCH-type zinc finger protein and F-box
      protein etc; early light-induced protein, which could protect and/or repair the
      photosynthetic apparatus damage induced by stress; cysteine proteinase and
      vacuolar processing enzyme that can make function in plant cell death, and lipid
      transfer protein precursor, polyubiquitin, chalcone synthase, NADP-dependent
      isocitrate dehydrogenase, salt-induced S12 protein, and oxygen-evolving enhancer
      protein 1 etc. Among 36 genes obtained, the proteins encoded three genes were
      homologous to 3 putative proteins: HAK2, calcium-binding protein and RNA-binding
      protein, respectively. In addition, 6 new salt stress response squences were
      found. The result indicated that the salt-tolerant mechanism of Tamarix
      androssowii may be a complicated, interactive system involving multiple
      approaches and multiple genes, but not only a single salt gland-depended
      approach.

PMID- 15493143
TI  - [Genetic diversity of common wild rice (Oryza rufipogon Griff) by using SSR
      markers and phenotypic traits in Guangxi Province].
AB  - In this paper, allelic variation and genetic diversity among geographies and
      growth habit types were studied by using 223 accessions of common wild rice
      primary core collection in Guangxi Province, with 34 SSR primers locating on 12
      chromosomes of rice and 19 phenotypic traits. In the results, 24.91 alleles were
      detected per locus on average with a range from 7 to 48. Compared to the
      cultivated rice, the wild rice showed more allelic variations. The ratio of
      heterozygote of SSR locus was 32.01% on average, and it's range was 1.35% 81.31%.
      The frequency of heterozygote of SSR locus in Oryza rufipogon Griff was much
      higher than in Oryza sativa L. The geographical distribution of genetic diversity
      measured by SSR markers was not completely accordant with that by phenotypic
      traits. At DNA level, more wild rice individuals and higher genetic diversity
      were included within the area covering north latitude 22 degrees - 23 degrees and
      23 degrees - 24 degrees (comprising Longan, Fusui, Yongning, Xiangzhou, Laibin,
      Xuanwu, Yulin and Guigang county), which formed the center of genetic diversity.
      But the center of genetic diversity at the phenotypic level located within north
      latitude 21 degrees - 22 degrees and 22 degrees - 23 degrees. Among the four
      growth habit types, the genetic diversity from high to low was found respectively
      in prostrate type, sloping type, slighting type, and erect type at both DNA and
      phenotypic levels.

PMID- 15493144
TI  - Significant associations of the alpha-adducin gene Gly460Trp polymorphism with
      serum bilirubin concentrations in Chinese essential hypertension patients.
AB  - We investigated associations of the Gly460Trp polymorphism of the alpha-adducin
      gene and concentrations of serum total bilirubin, serum direct bilirubin and
      serum unconjugated bilirubin in patients with essential hypertension from Anhui,
      China from September 2000 to January 2001. Compared to women with the Gly/Gly
      genotype and after adjustment for important covariates, women with the Trp/Trp
      genotype had lower mean concentrations of serum total bilirubin (beta = -1.2
      micromol/L; P = 0.01), serum direct bilirubin (beta = - 0.4 micromol/L; P = 0.02)
      and serum unconjugated bilirubin (P = -0.8 micromol/L; P = 0.03). Among women in
      either the upper or lower quartiles of serum total bilirubin, serum direct
      bilirubin and serum unconjugated bilirubin and compared to those with the Gly/Gly
      genotype, women with the Trp/Trp genotype had higher odds of being in the lower
      quartile of concentrations of serum total bilirubin (odds ratio = 4.0; 95 percent
      confidence interval: 1.6 - 10.2; P < 0.01), serum direct bilirubin (odds ratio =
      4.0; 95 percent confidence: 1.6 - 9.7; P < 0.01) and serum unconjugated bilirubin
      (odds ratio = 2.7; 95 percent confidence interval: 1.1 - 6.7; P = 0.03) after
      adjustment for important covariates. We did not observe any significant
      associations in these models for men. We concluded that the Trp/Trp genotype of
      alpha-adducin Gly460Trp was associated with lower serum bilirubin concentrations
      in this group of Chinese women with essential hypertension. Women with the
      Trp/Trp genotype of alpha-adducin Gly460Trp might have increased risk for
      cardiovascular diseases due to lower concentrations of serum bilirubin.

PMID- 15493145
TI  - [Molecular characterization of mutations and phenotype/genotype correlation in
      Chinese patients with 21-hydroxylase deficiency].
AB  - To investigate characteristics of CYP21 mutations in Chinese patients with 21
      hydroxylase deficiency (21-OHD) and the relationship between genotype and
      phenotype, a time saving, reliable molecular diagnosis method was developed.
      Eight patients with NC 21-OHD, 35 patients with classical ones and 34 normal
      controls were studied as followed: CYP21 gene was amplified into fragment 1
      (exon1 --> exon3) and fragment 2 (exon3 --> exon10) through PCR with specific
      primers. The second round PCR was carried out using fragment 1 and 2 as template,
      and PCR products were digested by restrictive enzymes to analyze nine mutations,
      including Del, Exon3 Del8 bp, Q318X, R356W, Exon6Cluster, i2g, l172N, P30L and
      V281L. The most frequent mutation in 43 cases of Chinese 21-OHD was l172N
      (36.0%), followed by i2g (20.9%), Del (8.6%), P30L (7.0%), Q318X (7.0%), V281L
      (4.7%), R356W (2.3%), E6Cluster (2.3%) and Exon3 Del8 bp (1.2%). The most common
      CYP21 gene defect in salt wasting, simple virilizing and nonclassical form was
      Del (44.4%), l172N (44.2%) and P30L (37.5%) respectively. In addition, genotype
      was classified into three (severe, moderate and mild) groups according to the
      degree of 21-hydroxylase enzymatic compromise caused by the mutation. Age of
      first visit, basal 17-OHP, composition of disease subtype were significantly
      different among the three groups, P < 0.05. In conclusion, the most common
      mutations in Chinese 21-OHD were l172N, i2g and Del. The genotype of Chinese 21
      OHD has strong correlation with the phenotype.

PMID- 15493146
TI  - [Screening of differential genes between human embryonic stem cell and
      differentiated cell].
AB  - It is one of the core questions that how human embryonic stem cell (hESC)
      maintain the undifferentiated state during the propagation process. The current
      advance in answering this question included the studies on LIF signal
      transduction, Oct-4 factor and Nanog gene. But the question is far from being
      elucidated. In order to further understand the mechanism of maintaining the
      undifferentiated state of hESC, we screened out the expressed sequence tags
      (ESTs) which expressed highly in hESC but expressed lowly or unexpressed in the
      differentiated hESC's clones (dhESC) by suppression subtractive hybridization
      (SSH) and cDNA dot blot techniques. One hundred and five putative positive clones
      were screened out to be sequenced and were compared with the GenBank. Among them,
      seventy six clones represented sixty one identified genes that shared high
      homology with sequences in GenBank. Eighteen clones represented fifteen
      hypothetic genes, and eleven clones were function-unknown. Eight clones were
      picked out to analyze using semi-quantitative RT-PCR, the results confirmed that
      the expression of seven clones among them were higher in the hESC, and lower or
      no expression in the dhESC. The results showed that many differentiated expressed
      genes were involved before and after hESC's differentiation. Further functional
      analysis to those genes that expressed highly in the undifferentiated hESC and
      lowly in the dhESC might provide a basis to understand the mechanism of
      maintaining the undifferentiated state of hESC.

PMID- 15493147
TI  - [Cloning and expression of pituitary prolactin gene in Ailuropoda melanoleuca].
AB  - The giant panda (Ailuropoda melanoleuca) is an endangered species and indigenous
      to China. It has been proposed that it has a highly specialized reproductive
      pattern with low fecundity, but little is known about its basic reproductive
      biology at molecular level. In this study,the pituitary prolactin (PRL) cDNA of
      giant panda was amplified by RT-PCR from pituitary total RNA and then cloned,
      sequenced and submitted to GenBank (GenBank accession No. AY161285). The sequence
      analysis revealed that the giant panda prolactin cDNA contains a 687-nucleotide
      open reading frame encoding the prolactin prohormone of 229 amino acid residues.
      The signal peptide contains 30 amino acid residues and the mature prolactin is
      composed of 199 amino acid residues. Then the DNA fragment amplified was
      subcloned into pGEX-4T-1 procaryotic expression plasmid and protein expression
      was induced by IPTG in Escherichia coil BL21. SDS-PAGE analysis revealed the PRL
      protein is infusible. The multiple sequence alignments revealed that the homology
      of giant panda is 95% to cat and pig, 80% - 70% to human, cow and goat, 52% to
      rat and 45.9% to mouse at the amino acid level. The 64th amino acid of giant
      panda prolactin is hydrophilic serine instead of hydrophobic proline of cat,
      goat, and cow or hydrophobic alanine of human.

PMID- 15493148
TI  - [Divergence and systematical evolution of three Leuciscus species in Xinjiang
      based on mitochondrial DNA control region sequences].
AB  - Nucleotide sequence of fish mitochondria DNA (mtDNA) D-loop region from Leuciscus
      leuciscus baicalensis, L. merzbacheri, and L. idus in Xinjiang, China, were
      examined by sequencing 667 - 669 bp length of homological fragments in the D-loop
      from 24 individuals of the three fish species. DNA divergence ranged from 6.39% -
      9.89% among the three fish species in the genius of Leuciscus cuvier. The
      sequence similarity is high and the variation is low between L. Leuciscus
      baicalensis and L. idus. In contract, the genetic distance is larger between L.
      Leuciscus baicalensis and L. merzbacheri. The average nucleotide variation within
      each of the two geographical populations (Sailimu lake and E' erqis river) of L.
      leuciscus baicalensis is 1.07% and 1.08%, respectively, and such variation is
      1.07% between the two populations. These results demonstrate that the two
      geographic populations of L. leuciscus baicalensis do not appear to have
      significant genetic differentiation. Sequencing data showed the existence of
      sufficient genetic variations among three species of fish, as illustrated by
      distinct haplotypes for each species. The phylogenetic trees built with MEGA1.02
      pointed out that the relationship between L. leuciscus baicalensis and L. idus is
      close, and L. merzbacheri is ancient among three Leuciscus.

PMID- 15493149
TI  - [The genetic evidence for sympatric speciation pattern of Cyprinus from Erhai
      Lake].
AB  - In the present paper, mtDNA RFLP and mtDNA D-loop sequencing were investigated in
      three species of Cyprinus from Erhai Lake. The results indicated that two mtDNA
      haplotypes were identified in three species of Cyprinus from Erhai Lake by using
      16 restriction endonucleases. All individuals share the dominant type I except
      one individual of C. longipectoralis shows type II just with only one cleavage
      site polymorphism when tested by Dra I. Compared to the reported interspecific
      and intraspecific sequence divergence in fishes, the present divergence values of
      0% - 0.0075% from the Cyprinus species native to Erhai Lake were too much lower.
      Furthermore, 449 bp of mtDNA D-loop region sequencing was investigated in these
      three Cyprinus species. There were six mtDNA haplotypes indicated by seven
      variation sites. The interspecific sequence divergence were 0.082% - 0.171%. It
      is also at least one degree lower than some allopatric Cyprinus species we
      studied. A remarkably low level of genetic divergence detected among the three
      species of Cyprinus species in Erhai Lake both by mtDNA RFLP and D-loop region
      sequencing provides direct genetic evidence for its sympatric speciation pattern,
      which could occurred without progressive adaptive genetic variation.

PMID- 15493150
TI  - [New progresses on mitochondrial DNA in fish].
AB  - The study on mitochondrial DNA (mtDNA) is a hot field in recent molecular
      biology. With some special characteristics, mitochondrial DNA as an ideal genetic
      marker has been successfully applied to the research of population and
      evolutionary biology of fish. Many scientific achievements on mtDNA in fish have
      been made, however, a number of issues need to be further studied and explored.
      In the present paper, the research progresses on the complete mtDNA sequences,
      the structures and characteristics of mtDNA, the mtDNA control region structures,
      and mtDNA polymorphisms and detecting methods are introduced. Furthermore,we
      review the applications in the recent years in the fields of systematic
      evolution, hybridization and introgression, biogeography and population genetics
      of fish.

PMID- 15493152
TI  - [Image of the month. Adnexitis on bilateral hydrosalpinx].

PMID- 15493151
TI  - [Image of the month. Myxoma of the left atrium].

PMID- 15493153
TI  - [How I prevent erysipelas and its consequences and recurrences].
AB  - Erysipelas is a serious infection of the skin. In case of delay in initiating
      adequate antibiotic treatment, complications, sometimes dismal, can supervene. In
      addition, erysipelas shows a tendancy to recurrences. The prevention of an
      episode of erysipelas calls for correct personal hygiene and adequate use of
      topical antiseptics in case of skin effraction, even when minimal. When
      erysipelas is established, a rapidly initiated antibiotic treatment for a
      prolonged period prevents streptococcal gangrene complications. Elastic
      contention of any leg edema from venous or lymphatic origin and prophylactic
      antisepsis of discrete wounds help in preventing erysipelas recurrences.

PMID- 15493154
TI  - [Syphilis: a STD back to us].
AB  - Sexually transmitted diseases (STD) show frequent epidemiological changes. We
      report a case of secondary syphilis diagnosed in a 32-year old woman during post
      partum. The disease, although showing a typical presentation, raises the problem
      of dating with precision the contamination time. This is of importance for
      treating the newborn at risk of congenital syphilis. We highlight the constant
      attention that should be brought to disclose this venereal disease that shows so
      variable clinical and histological presentations. Syphilis seems on the rise in
      the Mosan valley and in some cities where prostitution is imported from Eastern
      Europe and Africa.

PMID- 15493155
TI  - [Anatomo-clinical confrontation: idiopathic pulmonary fibrosis].
AB  - Idiopathic pulmonary fibrosis and pulmonary fibrosis associated with systemic
      diseases are the most frequent diffuse interstitial pulmonary diseases. They
      slowly but irrevocably progress towards terminal respiratory failure. They can
      also be complicated by severe acute respiratory failure and admission in the
      intensive care unit can be discussed. Despite invasive mechanical ventilation,
      anti-infectious and immunosuppressive treatments, the disease carries a high
      mortality rate. We report and discuss the case of a patient with idiopathic,
      pulmonary fibrosis (UIP) who underwent rapid clinical deterioration.

PMID- 15493156
TI  - [Myocardial reinnervation after heart transplantation].
AB  - Despite many studies, cardiac reinnervation after heart transplantation is not
      yet fully understood. This article reviews the physiology of the transplanted
      heart and briefly describes the imaging techniques and functional tests which
      allow demonstration of cardiac reinnervation. The data reported on this subject
      in the literature are summarized and the remainin uncertainties are underlined.

PMID- 15493157
TI  - [Heart and androgens].
AB  - Beyond sexual function regulation, male steroids are operative in several
      physiologic homeostastic systems including the cardiovascular system. By ways of
      specific androgen receptors,testosterone can mediate cardiomyocyte trophycity, in
      physiologic states as in diseases involving cardiac hypertrophy. Androgenic
      hormones also regulate pathologic levels of inflammatory cytokines as 11-6 or
      TNF, in advanced heart failure. They also mediate vascular resistance with, in
      vitro and in vivo, proved coronary vasodilatation. Reduced free testosterone
      serum levels (age-mediated or in premature coronary artery disease patients (CAD)
      promote a pro-atherogenic lipid profile expressed as HDL-cholesterol decrease and
      up-regulation of triglycerids levels). The latter observation has relevant
      clinical significance for evaluation and treatment of CAD disease. As most of
      normal and diseased cardiovascular system functions are influenced by androgens,
      we can foresee an increasing interest for further evaluation of their physiologic
      implications as well as for large and rigourous studies of their therapeutic
      potential in two leading disabling pathologies, CAD and heart failure.

PMID- 15493158
TI  - [Video-capsule endoscopy for small bowel investigation].
AB  - Capsule endoscopy is a new technique of exploration which enables to visualize
      the entire small bowel. Occult or unexplained digestive bleeding currently
      constitutes on major indication of this technique. The aim of this study is to
      report the results obtained among 15 patients investigated by capsule endoscopy
      and to discuss the place of this new technique in the small bowel exploration.

PMID- 15493159
TI  - [Intra-abdominal desmoplastic small round cell tumor. A case report].
AB  - Intra-abdominal desmoplastic small round cell tumor is an extremely rare and
      aggressive neoplasm that predominantly occurs in young adult men; it has an
      uncertain histogenesis, and predominant or exclusive intra-abdominal localisation
      without visceral origin involvement. This tumor is characterized by its distinct
      morphology and its multiphenotypic differentiation. We report a case of an intra
      abdominal desmoplastic round cell tumor in a 24 years old woman. In the light of
      this case, the clinical morphological immunohistochemical and molecular of this
      rare desease are revewed.

PMID- 15493160
TI  - [Outcome of delivery at extreme ages of reproductive life].
AB  - BACKGROUND: Deliveries in adolescents and in elderly are separately known as
      associated with high foetal and maternal risks. The purpose of this study was to
      test the hypothesis that the outcome of deliveries might be comparable in these
      distinct age groups. POPULATION AND METHODS: The deliveries of 99 adolescents
      aged 16 and under were compared with that of 183 women aged 40 years and above
      with respect to complications of the delivery and the outcome of pregnancy. Data
      collection was retrospective using delivery room registers from 01/01/1991 to
      31/12/2000. RESULTS: Some risks were comparable in both groups as delivery by
      caesarean section, intra uterine growth retardation, and stillbirth. Other risks
      were significantly higher in teenagers as post-term delivery, premature delivery,
      and neonatal foetal distress. The risk of macrosomia was significantly higher in
      aged women. CONCLUSION: There are risks that are similar in both extremes of age.
      Other risks are higher particularly in teenagers or in aged women. A common
      prenatal care unit can be used for these two categories of population, but a few
      different practices will have to be considered according to the specific age
      group.

PMID- 15493161
TI  - [How I explore...the absolute cardiovascular risk at 10 years: from Framingham
      1998 to SCORE 2003].
AB  - Prevention of cardiovascular diseases should primarily focus on high-risk
      individuals. In the absence of atherosclerosis manifestations, such persons may
      be screened by the calculation of the absolute risk of complications during the
      next ten years or extrapolated at the age of 60 years. This calculation is based
      upon the analysis of most important risk factors of atherosclerosis. The mode of
      calculation that prevailed for many years used the Framingham equation
      determining the absolute coronary risk (both morbidity and mortality) in the next
      10 years: a risk equal or superior to 20% is considered as high and requiring
      specific intervention. The Third Joint Task Force of European and other Societies
      on cardiovascular disease prevention in clinical practice recently proposed a new
      mode of calculation (SCORE) based upon the absolute risk of cardiovascular (and
      not exclusively coronary) mortality (only fatal events and not morbidity):
      according to SCORE, the threshold of high risk has been set at a risk equal or
      superior to 5% in the next 10 years. The present article compares the two modes
      of calculation with their own advantages and disadvantages.

PMID- 15493162
TI  - Role of lymphadenectomy in management of adenocarcinoma of the endometrium.
AB  - PURPOSE: To review the role of lymphadenectomy (LND) for patients with
      endometrial adenocarcinoma. METHODS: A review was undertaken of the English
      Language literature dealing with the role of LND for patients with endometrial
      adenocarcinoma (EC). RESULTS: The prognostic value of node status for EC patients
      has been recognized. LND performed by experienced surgeons has acceptable
      morbidity. Multiple series have suggested that significantly less external beam
      radiation is given to patients with known negative nodes. The decreased use of
      postop whole pelvic radiation has potential cost savings. However a survival
      advantage for LND has not yet been proven in a randomized clinical trials. United
      Kingdom investigators have begun a trial to determine if there is a demonstrable
      survival advantage for EC patients who undergo LND. CONCLUSION: Although the
      morbidity, potential cost savings, and prognostic impact of node status are well
      accepted, it remains controversial as to whether LND provides a survival
      advantage. Trials are underway.

PMID- 15493163
TI  - Tota mulier in mamma (The whole woman is in her breast).

PMID- 15493164
TI  - Hepatic metastasectomy as a cytoreductive strategy for the treatment of liver
      metastases in breast cancer: review of literature.
AB  - The resection of liver metastases in breast cancer patients is a controversial
      therapeutical approach. No data of prospective randomized trials are available,
      thus evidence for the potential role of hepatic metastasectomy rests on
      retrospective studies with a small number of patients. Techniqual advances
      however have rendered hepatic metastasectomy safe and the long-term results of
      some studies possibly support the role of a surgical approach in selected
      patients.

PMID- 15493165
TI  - The role of tumor markers in non-palpable breast cancers.
AB  - Screening mammography and clinical breast examination are the best tools
      available for the diagnosis of breast carcinomas in asymptomatic women. Many
      studies have attempted to determine the pathological and biological
      characteristic findings in screening-detected cancers. Tumor size, histologic
      type, cytological grading and lymph node status have an important role in
      estimating the biological profile of non-palpable breast cancers. Tissue tumor
      markers, such as proliferation markers, hormone receptors, c-erbB-2 and p53
      oncoproteins, bcl-2 gene and angiogenesis-related markers do not seem to
      distinguish mammographically detected tumors from clinically presented cancers.
      Further studies are needed to assess the prognostic role of certain biological
      factors in well-designed clinical studies along with long follow-up of screened
      patients.

PMID- 15493166
TI  - Inhibitors of angiogenesis in therapy of ovarian cancers.
AB  - The capacity to induce growth of blood vessels represents one of the phenotypic
      traits of neoplastic cells. Several preclinical studies prove that the inhibition
      of growth of peri-neoplastic blood vesssels leads to restricted growth of primary
      tumours and of metastases. Nevertheless, clinical studies indicate that
      angiogenesis inhibitors are not such effective drugs as might be expected on the
      basis of studies conducted on animals. In this article we would like to draw the
      readers' attention to divergencies between preclinical and clinical results, in
      particular to those related to ovarian cancers. In the treatment of ovarian
      cancers, angiogenesis inhibitors combined with other drugs may prove to represent
      a relatively effective therapeutic approach.

PMID- 15493167
TI  - Diagnostic value of ultrasound and color Doppler in identifying axillary lymph
      node metastases in patients with breast cancer.
AB  - PURPOSE: The aim of this study was to evaluate the diagnostic ability of
      ultrasound and color Doppler in axillary lymph node metastases of patients with
      breast cancer. MATERIAL AND METHODS: A prospective study including 55 patients
      with primitive, invasive, node negative breast cancer who underwent preoperative
      axillary ultrasound and color Doppler. Doppler and morphologic ultrasound
      criteria were applied to the identification of axillary lymph node metastases.
      RESULTS: The imagery study of all 55 patients identified a total of 141 nodes; 44
      were considered to be positive according to established criteria. The
      histological examination of the axillary dissection revealed a total of 989
      nodes; 77 out of 989 presented metastases; all invaded nodes belonged to 21
      patients. The previous imagiologic study was positive for axillary lymph node
      metastases in 15 out of these 21 patients. A sensitivity of 71.4%, a specificity
      of 71.4%, a negative predictive value of 80.6% and a positive predictive value of
      60.0% were achieved. CONCLUSION: The imagery study of the axillary region through
      ultrasound and color Doppler might be useful in assessing axillary lymph node
      metastases in patients with breast cancer.

PMID- 15493168
TI  - Stage I ovarian cancer: comparison of laparoscopy and laparotomy on staging and
      survival.
AB  - OBJECTIVE: The aim of this study was to compare staging accurateness as well as
      survival when managing early ovarian cancers by laparoscopy or laparotomy.
      MATERIAL AND METHODS: We have conducted a retrospective and multicentric study in
      France. Only Stage I ovarian epithelial cancers operated on from January 1, 1985
      to December 31, 1999 were taken into account. Respondents had to fill in a form
      detailing in each case the surgical access; the surgical acts performed during
      the initial intervention as well as data on the patient's follow-up. Lack of
      follow-up or final Stage > I were considered as exclusion criteria. Data were
      recorded and analysed with SPSS 7.5 and STATA (Stata statistical sofware 7.0).
      (ANOVA, chi-square test or Fisher's exact test and log-rank test). RESULTS: 105
      cases were included: 14 patients were exclusively operated on by laparoscopy
      (group 1), 13 other patients were subjected to a conversion from laparoscopy to
      laparotomy (group 2) and 78 patients exclusively underwent laparotomy (group 3).
      Patients in group 3 were significantly more frequently postmenopausal and had
      larger lesions. Cyst rupture was rare during laparoscopy (21%) and the use of an
      endobag was achieved in only 21% of the patients in group 1. Radical treatment
      was significantly more frequent in group 3 when compared to group 1 (67% vs 23%,
      p < 0.05). Laparoscopy was not adequate for staging since no lymphadenectomy was
      carried out by this approach. However, only 27% of patients subjected to an open
      approach underwent lymphadenectomy and omentectomy. The outcome in terms of
      survival was similar in the three groups with a mean follow-up period of 1,221
      days (+/- 832) (p = 0.1). CONCLUSION: Laparoscopic management of early ovarian
      cancer is poorly efficient in staging although disease-free survival does not
      seem to be affected. Further evaluation of laparoscopy in this indication is
      needed.

PMID- 15493169
TI  - Human papillomavirus (HPV) testing in the management of women with abnormal Pap
      smears. Experience of a colposcopy referral clinic.
AB  - BACKGROUND AND OBJECTIVES: Several detailed algorithms for the appropriate use of
      human papillomavirus (HPV) testing in the management of women with abnormal Pap
      (Papanicolaou) smears have been launched, but their direct country-to-country
      adoption is difficult. This necessitates their testing in individual settings,
      which is ongoing in our colposcopy referral clinic. METHODS: A series of 224
      consecutive women attending the clinic with the usual referral indications (ASC
      US or higher in Pap) were examined by the conventional diagnostic tools (PAP
      smear, colposcopy, punch biopsy) and subjected to HPV testing and viral typing
      for both low-risk (L-R) and high-risk (H-R) types by nested PCR-based techniques.
      Predictors of the high-grade diagnostic categories were analysed using both
      univariate- and multivariate modelling, and the performance characteristics
      (sensitivity, specificity, NPV, PPV) of all tests in detecting high-grade CIN
      were calculated. RESULTS: In the PAP test, ASC-US smears were most common
      (37.9%), followed by low-grade squamous intraepithelial lesions (LSIL) (26.3%)
      and high-grade SIL (HSIL) (4.9%). Colposcopy was performed for 180 women, of whom
      48.3% had a normal transformation zone (TZ), 40.6% had ATZ1 (abnormal TZ grade
      1), and 5.6% had ATZ2. In biopsy (n = 71), 49.3% had CIN1, 5.6% CIN2, and 16.9%
      CIN3. The HPV test was positive in 64 (28.8%) women, more often in those aged <
      35 years (p = 0.025). High-grade colposcopy (ATZ2) was significantly associated
      with HSIL in the Pap test (OR 20.5; 95% CI: 4.34-96.47), and with HPV test
      positivity (OR 6.37; 95% CI: 1.58-25.73). The most significant predictors of CIN3
      were HSIL in the PAP, HPV test positivity, and high-grade colposcopy. HSIL and
      HPV test (for H-R types), but not colposcopy, retained their significance as
      independent predictors of CIN3 also in adjusted multivariate models: OR 88.27;
      95% CI 4.17-1867.04, and OR 19.46; 95% CI 2.01-187.75, for the HSIL and H-R HPV
      test, respectively. Changing the cut-off level of the Pap test from ASC-US to
      HSIL increased the specificity of the test up to 96.4%, with the loss in
      sensitivity from 87.5% to 43.8%. Colposcopy (ATZ2) had 92% specificity, and NPV
      competing with that of the Pap test. The sensitivity of HPV test exceeds that of
      the Pap test at HSIL cut-off level, but the specificity of the PAP test is
      clearly superior. CONCLUSIONS: Accurate predictors of significant cervical
      pathology (CIN3) are well defined, but the problem is the different performance
      of the diagnostic tools in clinical practice. A proficient combination of the
      tests is likely to result in the most satisfactory clinical practice in the
      management of women with abnormal Pap tests (MAPS).

PMID- 15493170
TI  - Cytogenetic abnormalities in serous papillary adenocarcinoma of the ovary.
AB  - PURPOSE OF INVESTIGATION: Epithelial ovarian tumors are usually mucinous or
      serous type, affecting nearly 1% of women during their lifetime. They may be
      regarded as benign, borderline or invasive according to pathological examination.
      Karyotypes of the tumor provide critical information about both the genetic
      predisposition and the stage of the tumor. We aimed to investigate the
      correlation between karyotype findings and the stage of the serous papillary
      tumors of the ovary. METHODS: Tissue cultures were set up from 15 serous
      papillary adenocarcinoma samples of different stages and examined
      cytogenetically. RESULTS: The most common chromosome abnormalities included both
      numerical and structural abnormalities of chromosomes 1, 3,6,7,8, 11, 21, 22 and
      X. CONCLUSION: Karyotypes became more complex, as expected, with the later
      stages.

PMID- 15493171
TI  - Outcome after treatment of high-grade squamous intraepithelial lesions: relation
      between colposcopically directed biopsy, conization and cervical loop excision.
AB  - PURPOSE OF INVESTIGATION: The hypothesis that cold-knife conization performed in
      women with high-grade squamous intraepithelial lesions (HSIL) and unsatisfactory
      colposcopy is a better procedure than the loop electrosurgical procedure (LEEP)
      is tested. METHODS: A retrospective study was conducted in conization specimens
      of women submitted to LEEP (n = 102) or conization (n = 245) due to HSIL. Age,
      biopsy, compromised surgical margins in conization, and recurrence were analysed.
      RESULTS: The frequency of invasion, non-compromised margins, and recurrence in
      conization and LEEP were, respectively, 7.7% versus 2.9%, 64.1% versus 48% (p =
      0.008), and 33.8% versus 24.1%. Eight (42.1%) and five (26.3%) of 19 women
      submitted to conization where invasion was found in surgical specimens were,
      respectively, menopausal or had unsatisfactory colposcopy. Twenty-five (96.2%) of
      26 and 23 (95.8%) of 24, respectively, undergoing conization and LEEP had
      recurrence in the first five years. CONCLUSION: We recommend the use of cold
      knife conization in cases where the lesion is located deep in the cervical canal.

PMID- 15493172
TI  - Is adjuvant therapy necessary for peritoneal cytology-positive surgical
      pathologic Stage I endometrial cancer? Preliminary results.
AB  - OBJECTIVE: To compare the clinical and laboratory findings between adjuvant
      therapy performed and not performed on peritoneal cytology-positive patients with
      cytology-negative cases of surgical-pathologic Stage I endometrial cancer.
      METHODS: Twelve peritoneal cytology-positive and 12 negative surgical-pathologic
      Stage I endometrial cancer cases were used in the study. Adjuvant radiotherapy
      was performed for six cytology-positive patients (group I); no adjuvant therapy
      was performed for six cytology-positive (group II) and 12 cytology-negative
      patients (control group). Pelvic examination, vaginal cytology, serum CA125
      levels and routine blood tests were checked at two-month intervals for two years
      and at six-month intervals for the third year. Abdominopelvic computerized
      tomography was planned annually. RESULTS: There was no statistically significant
      difference among the three groups and no recurrence in any group. CONCLUSION: We
      do not recommend adjuvant therapy for cytology-positive patients if the tumor is
      confined to the uterus.

PMID- 15493173
TI  - Assessment of ovarian tumors using transvaginal color Doppler ultrasonography.
AB  - In our study we used transvaginal color Doppler ultrasonography in a token of 127
      women presenting with unilateral ovarian tumor. The characteristics of the tumors
      were analyzed, the presence of vascularization was checked and the resistance
      index (RI) was calculated. Consequently, based on a concrete scoring system, we
      attempted to discriminate these tumors as benign or malignant. It was proven that
      24 of 127 ovarian tumors were malignant. Transvaginal color Doppler correctly
      identified 21 of the 24 malignant tumors, as well as 94 of the 103 benign tumors.
      In nine other cases we had false-positive results. The sensitivity and the
      specificity of the method was 87.5% and 91.2%, while the positive and negative
      predictive values were 70% and 96.9%, respectively.

PMID- 15493174
TI  - Low-dose 5-fluorouracil adjuvant in laser therapy for HPV lesions in
      immunosuppressed patients and cases of difficult control.
AB  - The authors established a protocol for the use of 5-fluorouracil (5FU) adjuvant
      in lasertherapy for clinical and subclinical HPV infection in immunosuppressed
      patients, persistent lesions and as reinforcement treatment in cases of poor
      progress. Sixty-four patients were evaluated, of whom 26 were immunosuppressed,
      34 presented persistent lesions and four received intravaginal reinforcement
      treatment with 2.5 g 5% 5FU every two weeks, or biweekly vulvar reinforcement
      after lasertherapy. On average, five 5FU courses were used, but in the
      immunossuppressed patients its use was maintained indefinitely. The rate of
      complete response was 66%, but the immunossuppressed patients showed less
      response (46.2%) when compared with the persistent lesion/reinforcement treatment
      group (78.9%). The responses were positive in the two groups when compared to
      that with no response. We deem the use of low-dose 5FU an excellent alternative
      in cases of difficult HPV progress, presenting a low cost and minimal side
      effects.

PMID- 15493175
TI  - Low-grade cervical squamous intraepithelial lesion during pregnancy: conservative
      antepartum management.
AB  - The purpose of this retrospective study was to determine the regression rate and
      management of low-grade squamous intraepithelial lesions (LSIL) in pregnancy.
      Seventy-four women with cytological findings of LSIL were analysed during the
      pregnant-puerperal period (until 12 months postpartum). Age, parity, cytological
      and colposcopic findings, route of delivery, and postpartum follow-up were
      studied. The age and parity of patients ranged (average) from 12 to 32 years
      (21.2 +/- 4.9), 0-5 (0.89 +/- 1.14), and 9-32 years (16.1 +/- 3.5), respectively.
      Thirty-nine of 55 (70.9%) and 12 of 19 (63.1%) pregnant women had normal cytology
      after vaginal delivery and caesarean section, respectively (p > 0.05). In
      postpartum, eight patients (10.8%) persisted with LSIL and ten (13.5%) presented
      high-grade squamous intraepithelial lesions. No case of unsatisfactory colposcopy
      and invasive carcinoma were found. LSIL during pregnancy has a high rate of
      regression, regardless of the route of delivery. Conservative management with
      colposcopic evaluation is proposed during gestation.

PMID- 15493176
TI  - AGUS and ASCUS: different incidence in pre- and postmenopausal women.
AB  - PURPOSE OF INVESTIGATION: The aim of this study was to determine the incidence of
      AGUS (atypical glandular cells of undetermined significance), ASCUS (atypical
      squamous cells of undetermined significance) and SIL (squamous intraepithelial
      lesion) in the cytologic diagnosis in pre- and postmenopausal women. METHODS: We
      did a retrospective study selecting 183 patients who were screened for cervical
      pathology. Ninety-six patients were in postmenopausal age. We determined the
      incidence of cytologic abnormalities defined as ASCUS, SIL, and AGUS in pre- and
      postmenopausal women. RESULTS: We expected a marked incidence of low-grade SILs
      in the fertile population, while the postmenopausal group was thought to be
      affected more by AGUS and ASCUS. We obtained different results. In our population
      study, premenopausal women presented more AGUS and ASCUS; the two subgroups
      presented the same incidence of low-grade SILs; postmenopausal women were more
      affected by high-grade SILs. CONCLUSIONS: The significance of the new categories
      introduced by the Bethesda System is still uncertain for different authors. As we
      look to the future new markers that more specifically identify individuals at
      risk can be expected.

PMID- 15493177
TI  - P53, c-erbB-2 expression and steroid hormone receptors in breast carcinoma:
      correlations with histopathological parameters.
AB  - OBJECTIVE: The aim of the study was to evaluate the p53 tumor suppressor gene, c
      erbB-2 and steroid hormone receptor expression in breast carcinoma by
      immunohistochemistry and to correlate them with different histopathologic
      parameters. MATERIALS AND METHODS: p53, c-erbB-2, steroid hormone receptors and
      their correlation with age, tumor size, histological grade, axillary lymph-node
      status, and menopausal status were investigated in 65 breast carcinoma cases. All
      markers were measured immunohistochemically on paraffin sections. Association
      between estrogen receptor (ER), progesterone receptor (PgR), p53 and c-erbB-2
      expression and clinicopathologic variables were assessed by the chi-square test
      for qualitative parameters. RESULTS: c-erbB-2 staining was found in 35.3% of
      breast carcinomas and was associated with ductal subtype and age under 35 (p =
      0.022, p = 0.003, respectively); p53 staining was seen in 27.6% of cases and was
      associated with high histological grade and postmenapausal status (p = 0.038, p =
      0.002, respectively). Progesterone receptor expression was associated with
      positive axillary status (p = 0.003). CONCLUSION: We concluded that expressions
      of c-erbB-2, p53, ER, and PgR may be used in the evaluation of breast carcinoma.
      Therefore the present study suggests that p53 expression is a marker of high
      histological grade in postmenopausal status, and that c-erbB-2 expression is
      associated with histologically ductal subtype.

PMID- 15493178
TI  - Primary fallopian tube carcinoma: a retrospective multicenter study.
AB  - PURPOSE: This retrospective multicenter study aimed to assess the survival and
      prognostic factors of primary fallopian tube carcinoma. METHODS: The medical
      records of 29 patients with fallopian tube carcinoma from two centers were
      reviewed for age, stage, surgical intervention, relapse and survival. RESULTS:
      The mean age of the patients was 56 years (range, 37-76). Six patients were in
      Stage I (20.7%), eight cases in Stage II (27.6%), nine cases in Stage III (31%)
      and two cases in Stage IV (6.9%). Data on stage was not available in four cases
      (13.8). Fifteen patients underwent lymph node evaluation. The median follow-up
      was 29 months (range, 3-122). The median survival was 95 months with a 5-year
      survival rate of 69.7%. The median progression-free survival was 76 months with a
      5-year survival rate of 51.8%. CONCLUSION: Age, stage and lymphadenectomy were
      found to be significant prognostic factors on overall survival.

PMID- 15493179
TI  - Atypical squamous cells: improvement in cytohistological correlation by the 2001
      Bethesda System.
AB  - PURPOSE OF INVESTIGATION: To evaluate the advantages of the 2001 Bethesda System
      over the 1991 Bethesda System in the management of atypical squamous cells.
      METHODS: The cytology files of the 8,748 patients were reviewed for diagnosis of
      atypical squamous cells of undetermined significance (ASCUS) at Zeynep Kamil
      Hospital. Seventy-two of the 259 smear specimens with the diagnosis of ASCUS were
      reviewed and reclassified according to Bethesda 2001. RESULTS: Of the 8,748
      specimens, 259 (2.96%) were diagnosed as ASCUS. In re-evaluation of the 72
      specimens according to the 2001 Bethesda system, the number of cervical smears
      with a diagnosis of atypical squamous cells (ASC) decreased to 21 in number. Of
      the 21 cervical smears with an ASC category, eight patients (38.1%) had high
      grade intraepithelial squamous lesions (HSIL) and six (28.6%) had low-grade
      intraepithelial squamous lesions (LSIL) in histopathological specimens. The
      detection rates of squamous abnormalities (chi2 = 24.79, p < 0.0001) and high
      grade squamous abnormalities (chi2 = 8.31, p = 0.0039) were significantly higher
      according to Bethesda 2001. CONCLUSION: The 2001 Bethesda System seems to reduce
      the number of cervical smear diagnoses of ASC, without causing any impairment in
      the diagnosis of HSIL thus decreasing the number of unneccesary interventions
      like cervical biopsy and decreasing the cost, inconvenience, anxiety and
      discomfort.

PMID- 15493180
TI  - Outcome at second-look laparotomy: anaesthesia related risk factors.
AB  - PURPOSE OF INVESTIGATION: To identify anaesthesia related risk factors associated
      with positive second-look laparotomy (SLL) findings in patients with epithelial
      ovarian carcinoma who had previous optimal cytoreduction surgery under general
      anaesthesia. METHODS: A retrospective review of the anaesthesia and medical
      records of patients with epithelial ovarian cancer who underwent SLL at our
      institution and analysis of patient related (age, haemoglobin, albumin),
      anaesthesia related (duration of anaesthesia, anaesthetics and dosages,
      transfusion of blood products), tumour related (stage, grade, presence of
      ascites, adhesion, histological type, capsule penetration and CA-125) data and
      outcome of SLL was undertaken. RESULTS: The patients had SLL 305 +/- 215 days
      after the first operation. Of the 83 patients 28 (33.7%) were SLL (+). SLL (+)
      patients were significantly more likely to have a mucinous histological subtype,
      required intraoperative packed red blood cell (PRBC) transfusion and longer
      anaesthesia duration (p < 0.05). Type of induction agent, whether narcotics were
      used or not, type of volatile agent used, dosages of induction agents and dosages
      of narcotic and muscle relaxants did not vary significantly between the patients
      with and without cancer recurrence (p > 0.05). Duration of anaesthesia (OR, 1.03;
      CI, 1-1.05, p = 0.031) and histological subtype (OR, 16.1; CI, 1.8-141.7, p =
      0.012), were the independent variables predicting cancer recurrence in the
      multivariate logistic regression. CONCLUSION: We emphasize that duration of
      anaesthesia and histological subtype are risk factors for cancer recurrence in
      early stage ovarian carcinoma. From our data it seems that interventions to
      shorten the duration of general anaesthesia or reversing immunosuppression
      induced by anaesthesia and surgery must be carefully considered.

PMID- 15493181
TI  - Normal colposcopy following abnormal Pap smear evoking LGSIL: a follow-up study.
AB  - The aim of this study was to determine the optimal treatment policy in women
      presenting with an abnormal Pap smear showing low-grade squamous intraepithelial
      lesion (LGSIL), who additionally had normal colposcopic findings. We
      prospectively studied 160 women with LGSIL and normal colposcopy, and divided
      them into two groups. Group A, consisting of 54 women, was followed-up for a mean
      period of 42 months and had a new control smear 12 months after the initial one.
      Group B, consisting of 106 women, was followed-up for a mean period of 44 months
      and had two consecutive control smears (6 and 12 months after the initial), and a
      new colposcopy, depending on the findings. At the end of the first year, the
      lesion persisted in 37% and 39% of the patients in groups A and B, respectively.
      At the end of the study, regression or persistence of the LGSIL was revealed in
      63% and 61% of the women in groups A and B, respectively. Aggravation of the
      lesions occurred after 16.5 and 15 months, respectively, in groups A and B. Our
      findings suggest that women with LGSIL and normal colposcopy do not need further
      therapeutic measures during the first year after the initial smear.

PMID- 15493182
TI  - Is there a change in serum CA-125 levels after laparoscopy?
AB  - There is no adequate data in the medical literature defining serum CA-125 levels
      after laparoscopy. Therefore we designed this prospective study to evaluate the
      effects of laparoscopy on serum CA-125 levels. Eighty-two women (mean age 34.2 +/
      12.30 years) were included in the study between January, 2001 and April, 2003.
      Laparoscopies were performed in patients with chronic pelvic pain, dysmenorrhea,
      infertility, ovarian cysts and for tubal ligation. Mean serum CA-125 levels of
      the patients before and after the laparoscopic procedures were 13.96 +/- 4.86
      U/ml and 14.02 +/- 4.96 U/ml, respectively. The change in serum CA-125 levels
      prior to laparoscopy was statistically insignificant when compared with the
      levels obtained at 24 hours after laparoscopic procedure (p > 0.05). We found
      that diagnostic laparoscopy or laparoscopic surgical procedures did not change
      the levels of CA-125 at the 24th hour after laparoscopy indicating either serum
      CA-125 levels are not correlated, at least within 24 hours, with peritoneal
      irritation or peritoneal irritation is minimal or absent in our operations.

PMID- 15493183
TI  - Prevention of cyclophosphamide-induced ovarian damage by concomitant
      administration of GnRHa in mice: a dose-dependent relationship?
AB  - OBJECTIVE(S): This experimental study investigates the dose-related effects of
      cyclophosphamide (Cy) on primordial follicular reserve in young mice, and
      examines whether the concomitant administration of a gonadotropin-releasing
      hormone agonist (GnRHa) may protect gonadal reserve, even at different doses of
      Cy. METHODS: Forty sexually mature virginal Balb/c mice aged five to six weeks
      were administered different doses (0, 50, 75,100 mg/kg) of Cy. Another 40 animals
      were treated with increasing doses (0, 50, 75, 100 mg/kg) of Cy in combination
      with GnRHa. GnRHa treatment was initiated one week prior to chemotherapy and also
      continued after chemotherapy for one week. The ovaries were removed seven days
      after Cy administration and the total number of primordial follicles in both
      ovaries was counted. RESULTS: Primordial follicular destruction occurred at all
      levels of Cy exposure. There was a positive correlation between increasing doses
      of Cy and higher proportion of follicular loss (p < 0.0001). GnRHa was not able
      to protect against the chemotherapy-induced negative effect on primordial
      follicular count at low doses (50 mg/kg and 75 mg/kg). Mean +/- SD primordial
      follicle count in the 100 mg/kg Cy-treated group was significantly lower than in
      the 100 mg/kg Cy + GnRHa treatment group (73.9 +/- 33.1 vs 89 +/- 17.9, p =
      0.047). CONCLUSION: Our data suggest a possible ovarian protective effect of
      GnRHa cotreatment only at high doses of Cy treatment. However, in spite of co
      administration of GnRHa, loss of primordial follicular reserve occurred at all
      doses of Cy in mice.

PMID- 15493184
TI  - Borderline tumor of the lymph node associated with bilateral serous borderline
      tumor of the ovary: case report.
AB  - The pathological diagnosis of a patient who was operated on for ovarian cancer
      was serous borderline tumor of the ovary. At the same time, pathological
      examination of one of the paraaortic lymph nodes revealed borderline tumor of the
      lymph node. We also searched the literature associated with this case.

PMID- 15493185
TI  - Chemotherapy for ovarian mucinous cystadenocarcinoma during pregnancy: a case
      report.
AB  - There is limited experience in the treatment of epithelial ovarian malignancy
      with chemotherapy during pregnancy. We present the case of a 36-year-old women
      with ovarian mucinous cystadenocarcinoma during pregnancy, on whom exploratory
      laparotomy was performed at the gestational age of 16 weeks. Afterwards
      chemotherapy with cyclophosphamide (500 mg/m2) and cisplatin (50 mg/m2) was
      administered beginning at the second trimester of pregnancy due to surgical Stage
      Ic. Although preterm labor and a prematurely ruptured membrane occurred at the
      gestational age of 29 weeks before the fourth course of chemotherapy, there was
      still a satisfactory outcome for mother and fetus after an emergency cesarean
      section due to breech presentation at the gestational age of 30 weeks.

PMID- 15493186
TI  - Failure of imaging techniques in revealing breast cancer progression.
AB  - This study focuses on a case of a 67-year-old woman with occult breast cancer
      involving the axillary lymph nodes. The instrumental examinations employed,
      positron emission tomography included, were not useful in diagnosing the disease.
      When the patient was surgically treated micro-invasive breast cancer was
      diagnosed. This peculiar malignant pathology is a matter of discussion especially
      because it is hardly diagnosable. Because of such diagnostic difficulties it may
      happen that micro-invasive carcinoma progression can easily mislead routine
      diagnostic screenings performed on women over 50.

PMID- 15493187
TI  - Primary fallopian tube adenocarcinoma: preoperative diagnosis, treatment and
      follow-up.
AB  - Preoperative diagnosis of fallopian tube carcinoma is difficult due to the rarity
      and silent course of this neoplasm. We present herein the case of a 58-year-old
      woman with primary fallopian tube carcinoma that was diagnosed preoperatively on
      the basis of a positive for adenocarcinoma Papanicolaou vaginal smear, repeated
      episodes of vaginal bleeding, negative endocervical and endometrial curettage,
      characteristic features on ultrasonography and elevated CA-125 levels. The
      patient was treated by total abdominal hysterectomy, bilateral salpigno
      oophorectomy and omentectomy. Pathologic confirmation of primary serous papillary
      adenocarcinoma of the left fallopian tube was made. Peritoneal washings were
      positive for malignancy. FIGO stage was considered as IIIb and the patient
      received six courses of combined carboplatin-taxol chemotherapy. At two years
      from onset of therapy the patient underwent a modified radical mastectomy and
      lymphadenectomy because of primary carcinoma of the right breast. The patient was
      started on tamoxifen therapy, which she is still taking. At 60 months after
      initial surgery, the patient is alive and well. In conclusion, our study suggests
      an association between fallopian tube carcinoma and breast cancer and a good
      response of the patient to platinum-based chemotherapy.

PMID- 15493188
TI  - Two cases of rare malignant mesodermal uterine tumors. Diagnostic features
      analysis.
AB  - Two cases of uterine malignant mesodermal tumors are presented: a case of
      malignant fibrous histiocytoma (MFH) and a case of endometrial stroma sarcoma
      (ESS). The patients were 51 and 28 years old, respectively. The former died
      shortly after diagnosis. The latter is still alive. The macroscopic and
      microscopic features, clinical findings and the operations are reported and
      discussed, along with a review of the literature.

PMID- 15493189
TI  - Primary-adenocarcinoma of Bartholin's gland: a case report.
AB  - Up to now, about 300 primary adenocarcinoma carcinomas of Bartholin's gland have
      been reported in the literature. A new case of a 57-year-old woman with primary
      carcinoma of Bartholin's gland is reported. The patient underwent radical
      vulvectomy and has been healthy for 18 months.

PMID- 15493190
TI  - Primary ovarian carcinosarcoma: a case report and review of the literature.
AB  - Primary ovarian carcinosarcoma is characterized by an admixture of malignant
      epithelial and stromal elements. This neoplasm is extremely rare with fewer than
      400 cases reported in the English literature. Its histogenesis, clinical features
      and optimal treatment remain unclear because of the rarity of primary ovarian
      carcinosarcoma. This study focuses on the clinical, pathological,
      immunohistochemical features and survival of a 73-year-old patient with primary
      ovarian carcinocarcoma. The patient was treated with surgery followed by combined
      chemotherapy with carboplatin and taxol and assigned to FIGO Stage IIIc. She died
      from the disease 17 months after surgery. In conclusion, ovarian carcinosarcoma
      is a very aggressive tumor, especially when it is diagnosed at advanced stage.

PMID- 15493191
TI  - Extraovarian mullerian-type cystic tumors of the female. A report of six cases
      and review of the literature.
AB  - Six cases of extraovarian cystic tumors of mullerian type are reported. Patient
      age ranged from 27-71 years. Tumor diameters were 5-11 cm and were located in the
      mesentery (4/6) and retroperitoneum (2/6). Four tumors were of mucinous type (1/4
      of borderline malignancy) and two of serous type. These tumors clinically and
      histopathologically mimic other primary tumors of the peritoneum. The problems of
      differential diagnosis are discussed.

PMID- 15493192
TI  - [Gaining control again].

PMID- 15493193
TI  - [Nurses in the corridors].

PMID- 15493194
TI  - [Children can be told].

PMID- 15493195
TI  - [Fully engaged or inwardly prepared].

PMID- 15493197
TI  - [Protected career designation].

PMID- 15493196
TI  - [Do nurses earn too much?].

PMID- 15493198
TI  - [The basis of health care for the Land of a Thousand Hills].

PMID- 15493199
TI  - [Common career specialties for women].

PMID- 15493200
TI  - [Until there is an emergency...].

PMID- 15493201
TI  - [Emergencies: mirror of the society].

PMID- 15493203
TI  - [For when dreams become reality].

PMID- 15493202
TI  - [Going beyond the "match of improvization"].

PMID- 15493204
TI  - [Return to an active life--no problem!].

PMID- 15493205
TI  - [Delight and pain in knowledge].

PMID- 15493206
TI  - [*It is true, every time I pay attention, I am not comfortable"].

PMID- 15493207
TI  - [Thank you].

PMID- 15493208
TI  - [First aid: specialty of our society].

PMID- 15493209
TI  - [Protecting the professional title].

PMID- 15493211
TI  - Sampling issues in qualitative research.
AB  - While qualitative methodologies have increased in popularity over the past few
      decades, they have been criticised because of a lack of transparency in
      procedures and processes. While much of this criticism has been levied at
      analytical steps, many published qualitative studies give little information
      about the characteristics of the study sample or the type of sample employed or
      techniques used. In this paper, Gina Higginbottom aims to provide an overview of
      the complexity of sampling in qualitative research, and to provoke reflection and
      consideration of qualitative methodologies. It is hoped that this will encourage
      nurse researchers to seek out the primary texts and gain greater insight into the
      various philosophical underpinnings and sampling techniques in qualitative
      research.

PMID- 15493212
TI  - When is it safer to say nothing? Some considerations on biases in sampling.
AB  - In nursing research, once one has a solid design, one has still to think about-.a
      sampling strategy and implementation. Too often, the paraphernalia of inferential
      statistical reasoning is inappropriately deployed when the achieved sample can in
      no way be claimed to represent the drawn sample. Given the traditionally low
      rates of response in most nursing research (usually well under 90 per cent, and
      often unknown), there is a danger that perfectionist counsels would lead to an
      end to serious research. In this paper, Laurence Moseley and Donna Mead argue
      that such a nihilistic position is not necessary and that, instead, researchers
      should tailor their inferential analyses to the demands of any particular study.
      They argue that for many purposes, simple computations of both maximum and
      minimum population estimates are both defensible and useful.

PMID- 15493213
TI  - Researching the researchers: using a snowballing technique.
AB  - In this paper, Rosemarie Streeton, Mary Cooke and Jackie Campbell focus on an
      aspect of the needs and obligations of the UK Research Governance Framework (DoH
      2001). In particular, they discuss the snowballing recruitment technique and how
      this relates to the demands of research governance. The discussion is supported
      by examples from the literature and from the authors' own experiences in
      identifying research activity and skills across health and social care within a
      single health authority in the UK.

PMID- 15493214
TI  - Qualitative research sampling: the very real complexities.
AB  - In this article Anthony Tuckett discusses the complexities of qualitative
      research sampling. He analyses a research experience, together with the
      rationales for and limitations of qualitative research sampling. Further, he
      examines the reality of establishing and maintaining a purposeful/theoretical
      sample and how data saturation symbiotically interacts with constant comparison
      to guide sampling. Additionally sample limitations are countered. This paper is
      aimed at novice and experienced researchers in nursing interested in the
      practical reality of research, who are also mindful of the necessity for rigour.

PMID- 15493215
TI  - Methodological challenges in the study of psychological recovery from modern
      surgery.
AB  - Most cases of elective surgery in the UK are now undertaken in day-case
      facilities, and the trend is set to increase. Surgical and anaesthetic health
      care is changing rapidly. Traditional pre- and post-operative nursing
      intervention, once commonly taught and practised, must now be re-evaluated as a
      result of such transformations. However, undertaking research in order to
      investigate the fresh challenges facing nursing in the modern surgical
      environment may present many difficulties. Methodological issues, such as the
      application of research approaches, time for adequate data collection, and the
      utilisation of patients as participants undergoing modern surgery, will present
      numerous barriers. In this article, Mark Mitchell identifies and discusses three
      problematic methodological issues that currently challenge the effective study of
      psychological recovery from modern surgery in the UK.

PMID- 15493216
TI  - Making my mark.
AB  - Neil Brimblecombe explains how his first research project was carried out by
      accident, and how he has come to learn why stubbornness and resilience are such
      important characteristics for the nurse researcher to possess.

PMID- 15493217
TI  - Practice variation: implications for our health care system.

PMID- 15493218
TI  - Emerging therapies in anticoagulation.

PMID- 15493219
TI  - Therapy for systolic heart failure.

PMID- 15493220
TI  - The importance of anticoagulation management services.

PMID- 15493221
TI  - [Novel factors playing a role in the pathomechanism of diffuse liver diseases:
      apoptosis and hepatic stem cells].
AB  - Liver diseases can basically be categorised into the forms diffuse and focal. In
      case of diffuse liver diseases the damages in general affect the whole of the
      liver, but the alterations are usually present in varying degrees and severity.
      Relatively stereotypical reactions develop in the liver tissues on the effect of
      various damaging factors. Some of these reactions and their pathogenic
      backgrounds are well known, while others have only recently come into focus, like
      apoptosis and the regeneration-proliferation related hepatic stem cells. The
      number of damaging effects are naturally much higher than the number of possible
      response reactions and as a consequence, in many cases the etiological factors
      can not unambiguously be identified from the tissue alterations. The basic
      reaction types of the liver can be divided into well defined categories; thus
      adaptive changes, degeneration and intracellular storage, cell death
      (necrosis/apoptosis), inflammation, fibrosis and structural reorganisation, as
      well as regeneration/proliferation. The picture of "classic necrosis" is well
      known; with the detection of cellular swelling, membrane damage. Apoptosis is
      characterised by cell shrinkage, nuclear and cytoplasmic disruption, while the
      cell membrane remains intact. Apoptosis occurs in several liver diseases, with a
      striking form of appearance being the Councilman-like body seen in viral
      hepatitis. Apoptosis may have role in the pathogenesis of cholestasis, biliary
      atresia, the "vanishing bile duct syndrome", and alcoholic liver injury. The
      regenerative ability of the liver is excellent. The process is influenced by
      several growth factors and cytokines. In the case of chronic liver damage,
      however, the regeneration equilibrium becomes upset and irregular. Studies on
      liver regeneration have led to the recognition of hepatic stem cells. These cells
      of "oval" morphologic appearance are built up of a primitive structure, making
      them suitable for this task. Ductular proliferation originating from hepatic stem
      cells can mostly be recognised in three disease groups: liver regeneration
      following massive or submassive liver necrosis, ductular proliferation without
      liver insufficiency, and tumorous liver diseases. At present it is still unclear
      whether the hepatocyte formation originating from haematopoetic stem cells is a
      rarely occurring accidental transformation, or rather, under appropriate
      circumstances, a greatly effective "third" protective system. If the latter is
      true, this can fundamentally change our view on the pathomechanism of liver
      diseases, making possible numerous novel therapeutic treatments.

PMID- 15493223
TI  - [Level of fitness or physical activity as a modifying factor of cardiovascular
      risk].
AB  - Epidemiological data congruently verify that low fitness/low physical activity
      predisposes a higher probability for all-cause and cardiovascular death, compared
      to the normal and high-fit/active population. Measure of fitness or physical
      activity is an independent risk factor with at least the same weight as smoking,
      hypertension, dyslipidemia etc. therefore it is reasonable to involve it into the
      calculation of the risk chart. A couple of simple and inexpensive methods are
      available for measuring the fitness/physical activity. Any information in this
      field would help toward a better lifestyle.

PMID- 15493222
TI  - [New perspectives in the evolution of prognosis and treatment of chronic
      lymphocytic leukaemia].
AB  - Chronic lymphocytic leukaemia is a disease with a variable clinical course and
      prognosis. New prognostic factors like immunoglobulin gene mutational status,
      cytogenetic abnormalities, CD38 and ZAP70 expression of malignant cells have been
      described recently. Conventional and biological prognostic factors allow to
      identify patients with unfavorable prognosis at early stage. Purin analogues,
      fludarabine and fludarabine based combinations can achieve complete hematological
      remission in approximately one third of patients with chronic lymphocytic
      leukaemia. Chemoimmunotherapy (most experience is obtained by combination of
      fludarabine + cyclophosphamide + rituximab) can increase not only complete
      remission rate, but also induce molecular remission in some cases. Stem cell
      transplantation as well as early and effective chemotherapy are curative choices
      of treatment in patients with chronic lymphocytic leukaemia.

PMID- 15493224
TI  - [Phenotypic variants of A3243G mitochondrial DNA mutation in a Hungarian family].
AB  - The first Hungarian case with typical features of mitochondrial
      encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) in a young
      girl is presented. MELAS is a multisystem disorder inherited by the mitochondrial
      DNA with onset typically in childhood. Our patient presented the first symptoms
      at the age of 6 years with recurrent vomiting, nausea and transient visual loss.
      Several stroke-like episodes followed gradually impairing motor abilities and
      mental development. Molecular analysis of the mitochondrial DNA confirmed a
      heteroplasmic A3243G transition. The maternal family members were also tested for
      the mutation in peripheral blood DNA. In the mother of the proband, who suffers
      from bilateral hypacusis the mutation was detected in 20% of heteroplasmy, while
      in one of her asymptomatic sisters the mutation was present in 10% only. The
      bilateral hypacusis of the mother may be associated with this mutation and seems
      to differentiate the pedigree reported here from others published in the
      literature.

PMID- 15493225
TI  - [Chronic necrotizing pulmonary aspergillosis in an immunocompromised patient].
AB  - A case with chronic necrotizing pulmonary aspergillosis that was mimicking the
      radiomorphology of malignant tumor was reported. The patient was admitted to
      hospital with progression of a left upper lobe infiltrate which was known and
      under regular observation for 8 years, and haemoptoe. Computer tomography scan
      showed a spiculated abnormality in the left upper lobe with mediastinal
      lymphadenomegaly. Based on this finding pulmonary malignancy was suspected and,
      therefore, the patient was referred to surgical intervention. The post surgical
      histology revealed aspergillus in the specimen. Since signs of vascular invasion
      could not be detected microscopically and the disease developed in
      immunocompromised patient (due to diabetes mellitus and long term steroid
      treatment) the clinical condition was determined as chronic necrotizing
      aspergillosis. It is very likely that the pathogen infected the patient during
      his daily work in a bakery. The present paper also summarizes the clinical
      aspects, differential diagnosis and therapy of different forms of pulmonary
      aspergillosis with emphasis on chronic necrotizing pulmonary aspergillosis.

PMID- 15493226
TI  - [Management of valvular heart diseases].

PMID- 15493227
TI  - Pharmaceutical politics: the Senate ties itself in knots over cheaper drugs from
      Canada.

PMID- 15493228
TI  - Where they stand: health policy.

PMID- 15493229
TI  - Learning about fat: tackling childhood obesity in the schools.

PMID- 15493230
TI  - Looking for a hangover cure.

PMID- 15493231
TI  - Love her tender: when breast cancer strikes the woman in his life, a man needs a
      crash course in caregiving.

PMID- 15493232
TI  - Beginning reading intervention as inoculation or insulin: first-grade reading
      performance of strong responders to kindergarten intervention.
AB  - This study examined the first-grade reading progress of children who participated
      in an intensive beginning reading intervention in kindergarten. Specifically, the
      study investigated whether kindergarten intervention could prevent first-grade
      reading difficulties, or produce an "inoculation" effect, for some children under
      certain instructional conditions. Participants included children at risk for
      developing reading difficulties who received a 7-month beginning reading
      intervention in kindergarten. In October of first grade, 59 children who had
      achieved criterion levels on measures of phonological awareness and alphabetic
      knowledge were randomly assigned to one of two types of first-grade reading
      instruction: (a) code-based classroom instruction and a supplemental maintenance
      intervention, or (b) only code-based classroom instruction. February posttest
      measures assessed oral reading fluency, word reading, nonword reading, and
      comprehension. Between-group analyses indicated that instructional groups did not
      differ on any posttest measure. The students' absolute levels of achievement were
      compared to national and local normative samples. These results indicated that
      between 75% and 100% of students in both conditions attained posttest levels and
      demonstrated growth comparable to their average-achieving peers. These results
      support the hypothesis that strong responders to kindergarten intervention can
      experience an inoculation effect through the middle of first grade with research
      validated classroom reading instruction.

PMID- 15493233
TI  - Graphic organizers and their effects on the reading comprehension of students
      with LD: a synthesis of research.
AB  - Previous research studies examining the effects of graphic organizers on reading
      comprehension for students with learning disabilities (LD) are reviewed. An
      extensive search of the professional literature between 1963 and June 2001
      yielded a total of 21 group design intervention studies that met the criteria for
      inclusion in the synthesis. Using graphic organizers (i.e., semantic organizers,
      framed outlines, cognitive maps with and without a mnemonic) was associated with
      improved reading comprehension overall for students with LD. Compared to
      standardized reading measures, researcher-developed comprehension measures were
      associated with higher effect sizes. Initial gains demonstrated when using
      graphic organizers were not revealed during later comprehension tasks or on new
      comprehension tasks.

PMID- 15493234
TI  - Strategy development in children with mathematical disabilities: insights from
      the choice/no-choice method and the chronological-age/ ability-level-match
      design.
AB  - This study investigated the strategy characteristics and development of children
      with mathematical disabilities (MD) in the domain of simple addition and
      subtraction, in terms of Lemaire and Siegler's model of strategic change, using
      the choice/no-choice method and the combined chronological-age (CA)/ability-level
      (AL)-match design. Four groups of children, matched on either CA or mathematical
      AL, solved a series of 36 problems with the bridge over 10 in four conditions. In
      the choice condition, children could choose between retrieval, decomposition to
      10, and counting on to solve each problem. In the retrieval, decomposition, and
      counting conditions, they had to answer the same 36 problems using retrieval,
      decomposition to 10, and counting on, respectively. The results revealed clear
      differences in the frequency, efficiency, and adaptiveness with which the CA
      matched children applied the available strategies. In contrast, we observed no
      differences in strategy frequency, efficiency, and adaptiveness between the AL
      matched children. These results support the hypothesis that the strategy
      development of children with MD is marked by a delay rather than a specific
      deficit. Moreover, this study further documents the value of the methodology used
      to study children's strategy use and development in the domain of simple
      arithmetic.

PMID- 15493235
TI  - Writing performance assessments: how important is extended time?
AB  - Students in Grades 5 and 8 completed a 30-minute writing performance assessment
      and a writing performance assessment completed over 3 days. Assessments were
      evaluated on four traits (ideas, organization, conventions, and sentence
      fluency). A significant interaction was found at Grade 5 between length of time
      allotted for the assessment and students' educational classification (general or
      special education). Grade 5 students performed significantly better on the 3-day
      writing assessment, with students in special education benefiting the most. At
      Grade 8, there were no differences between scores on the 30-minute and the 3-day
      assessments. No significant differences were found in students' writing
      performance across various types of discourse (narrative, imaginative,
      persuasive, and expository); significant differences were reported across certain
      writing traits. We shared three hypotheses for reported differences: (a)
      students' proficiency with the writing process, (b) scoring scale bias, and (c)
      differences in the revision behaviors of developing and mature writers.
      Educational implications related to statewide test programs are discussed.

PMID- 15493236
TI  - Word processing as an assistive technology tool for enhancing academic outcomes
      of students with writing disabilities in the general classroom.
AB  - This study investigated the use of a word processor for enhancing the academic
      outcomes of three students with writing disabilities in a junior high school. A
      single-subject ABAB design was used to compare academic output produced during
      class time with and without a computer equipped with a word processor. The number
      of spelling errors, the number of reading errors, and the number of words used
      per text were counted, and the overall structure and organization of text were
      examined across all in-class materials. The data demonstrated a clear difference
      between handwritten and computer phases. In traditional paper-and-pencil phases,
      students produced outcomes that had more spelling mistakes, more reading errors,
      and lower overall quality of organization and structure in comparison with the
      phases in which a computer equipped with a word processor was used. The results
      did not indicate any noticeable difference in the number of words per text.
      Implications and future research directions are discussed.

PMID- 15493237
TI  - ADHD and reading disability in male adults: is there a connection?
AB  - The present study examined the comorbidity between attention
      deficit/hyperactivity disorder (ADHD) and reading disability (RD) in male adults.
      Participants were 120 men, of whom 24 were classified as having ADHD. The basis
      for the diagnosis was two self-report scales validated by interviews and
      background data. An extensive battery was used to assess phonological abilities
      and various aspects of reading skills. No differences were obtained between
      adults with and without ADHD on measures of either phonological processing skills
      or word decoding, indicating a low comorbidity with RD. This finding was valid
      even when different criteria were used to diagnose RD. However, the two groups
      differed in reading comprehension, with individuals with ADHD performing poorly
      in tests of reading comprehension. These results are compatible with the view
      that reading comprehension involves many of the higher cognitive control
      functions assumed to be impaired in ADHD. However, these attentional control
      functions are not critical to word recognition, which is determined by a more
      encapsulated phonological processing module. The pattern of associations between
      ADHD and RD observed in the present study is explained with reference to the
      differential attentional demands of the two aspects of reading.

PMID- 15493239
TI  - The effectiveness of a highly explicit, teacher-directed strategy instruction
      routine: changing the writing performance of students with learning disabilities.
AB  - This study examined the effectiveness of a highly explicit, teacher-directed
      instructional routine used to teach three planning strategies for writing to
      fourth and fifth graders with learning disabilities. In comparison to peers who
      received process writing instruction, children who were taught the three planning
      strategies-goal setting, brainstorming, and organizing-spent more time planning
      stories in advance of writing and produced stories that were qualitatively
      better. One month after the end of instruction, students who had been taught the
      strategies not only maintained their advantage in story quality but also produced
      longer stories than those produced by their peers who were taught process
      writing. However, the highly explicit, teacher-directed strategy instructional
      routine used in this study did not promote transfer to an uninstructed genre,
      persuasive essay writing. These findings are discussed in terms of their
      relevance to effective writing instruction practices for students with learning
      disabilities.

PMID- 15493238
TI  - College students classified with ADHD and the foreign language requirement.
AB  - The conventional assumption of most disability service providers is that students
      classified as having attention-deficit/hyperactivity disorder (ADHD) will
      experience difficulties in foreign language (FL) courses. However, the evidence
      in support of this assumption is anecdotal. In this empirical investigation, the
      demographic profiles, overall academic performance, college entrance scores, and
      FL classroom performance of 68 college students classified as having ADHD were
      examined. All students had graduated from the same university over a 5-year
      period. The findings showed that all 68 students had completed the university's
      FL requirement by passing FL courses. The students' college entrance scores were
      similar to the middle 50% of freshmen at this university, and their graduating
      grade point average was similar to the typical graduating senior at the
      university. The students had participated in both lower (100) and upper (200,
      300, 400) level FL courses and had achieved mostly average and above-average
      grades (A, B, C) in these courses. One student had majored and eight students had
      minored in an FL. Two thirds of the students passed all of their FL courses
      without the use of instructional accommodations. In this study, the
      classification of ADHD did not appear to interfere with participants' performance
      in FL courses. The findings suggest that students classified as having ADHD
      should enroll in and fulfill the FL requirement by passing FL courses.

PMID- 15493240
TI  - Using graphic organizers to attain relational knowledge from expository text.
AB  - Many students with learning disabilities (LD) experience difficulties with
      extracting relationships from expository text, especially if they are implicit.
      Results from studies with K-12 participants have been inconclusive regarding the
      potency of the graphic organizer (GO) as a comprehension tool. This study
      attempted to address some of the concerns with GO research by examining the
      effects of using GOs with middle school students with LD to convey and cue
      relational knowledge, using a longer intervention and using written essays to
      assess the students' attainment of relational knowledge. The results lend support
      for using GOs with students with LD to gain relational knowledge from expository
      textbooks. When factual knowledge was assessed via multiple choice tests and
      quizzes, no differences were found between treatment and control conditions. As
      in other GO studies, both groups demonstrated attainment of facts and concepts.
      But when relational knowledge was assessed, the two groups responded
      differentially. On essays that required application, the GO group provided
      significantly more relational knowledge statements than students in the No GO
      group did.

PMID- 15493241
TI  - The Swedish WAIS-R factor structure and cognitive profiles for adults with
      dyslexia.
AB  - Factor analysis of the Swedish version of the Wechsler Adult Intelligence Scale
      Revised (WAIS-R) on a group of 88 adult individuals with dyslexia showed a three
      factor structure with a verbal comprehension (VC) factor, a perceptual
      organization (PO) factor, and a freedom from distractibility (FD) factor. The
      results of this factor analysis support earlier findings from factor analyses of
      adults in the original U.S. normative sample and in different clinical groups.
      The profile of scores for the sample of individuals with dyslexia showed the
      expected pattern, with PO highest and FD lowest. The predicted pattern was also
      observed using Bannatyne's recategorization of WAIS-R subtests. As has been true
      for other typical and exceptional samples, women scored significantly higher than
      men on the Digit Symbol subtest. Related to this gender difference, Digit Symbol
      scores proved to be sensitive to problems associated with dyslexia only for men
      with dyslexia. Also, education level was shown to be related to verbal (V)
      performance (P) IQ discrepancy, with larger P > V differences observed for
      participants with fewer years of formal schooling. Regardless of these gender and
      education differences, the characteristic factor score and Bannatyne patterns
      were identified for both men and women and for three different subsamples
      categorized by educational level.

PMID- 15493242
TI  - Remedial interventions for children with reading disabilities: speech perception-
      an effective component in phonological training?
AB  - The effects of two types of phonological training in children with reading
      disabilities (RD) were examined. One of the programs (SP/LPA) trained children in
      speech discrimination, letter-sound correspondence, and phonemic awareness. The
      other program (LPA) trained children only in letter-sound correspondence and
      phonemic awareness. The effects of these programs were compared with a control
      group. Thirty-five children with RD were trained in small groups five times a
      week for 4 weeks. The results indicated that both experimental groups improved in
      phonemic awareness compared to the control group but that only the SP/LPA group
      scored higher than the control group in reading.

PMID- 15493243
TI  - Goal importance and students at risk of having language difficulties: an
      underexplored aspect of student motivation.
AB  - The purpose of this study was to compare the motivational determinants of
      students at risk of language difficulties (in reading and spelling) and students
      with high language skills. Teachers' evaluations in language and mathematics at
      the end of the academic year constituted the dependent variable. Motivational
      orientations were examined using the constructs that reflect the theory of
      planned behavior and goal importance. Participants were 202 elementary school
      students-22 at risk of language difficulties and 180 with high language skills
      drawn from 30 elementary schools in northern Greece. The results indicated that
      the two groups differed significantly, with the at-risk students exhibiting
      significantly lower perceptions of goal importance, intention to achieve, belief
      strength, outcome evaluation, and normative beliefs, and eventually scoring lower
      in language and mathematics at the end of the academic year. A finer analysis of
      students' motivational orientations was conducted using covariance structural
      modeling (CSM) and EQS 5.7b. The planned behavior model with goal importance
      produced a comparative fit index (CFI) of 1.00 in language and mathematics for
      the at-risk group. The respective CFIs for the high language skills group were
      .97 and 1.00 in language and mathematics, respectively. Although model fit was
      excellent across samples, different weights and signs linking motivational
      orientations to achievement partly explained the observed differences in language
      and mathematics manifested in the two groups.

PMID- 15493244
TI  - ADA-based accommodations in higher education: a survey of clinicians about
      documentation requirements and diagnostic standards.
AB  - The expansion of the number of students requesting accommodations in
      postsecondary settings compels clinicians to become knowledgeable about the legal
      definitions and documentation requirements of the Americans with Disabilities Act
      (ADA). Because the law is relatively new, courts and regulatory agencies have
      only recently begun to clarify what constitutes a disability. In this study, 147
      clinicians completed a questionnaire developed to assess their understanding of
      the law and the diagnostic approaches they used to justify claims of learning
      disability (LD), attention-deficit/hyperactivity disorder (ADHD), and psychiatric
      disability. Whereas the clinicians agreed on certain points (e.g., the right of
      institutions to formulate specific policies regarding documentation), they
      substantially disagreed on several fundamental issues. Clinician consensus was
      lowest on items that asked about the basic intent of the law, the metrics for
      assessing impairment, and the criteria for assessing ADHD in adulthood. Judged
      against the legislative history of the ADA and the body of regulatory rulings and
      legal decisions, many clinicians' responses showed a need for clarification
      regarding the distinction between special education law and the
      antidiscrimination intent of the ADA. The respondents also expressed a nearly
      uniform wish for more training in this fast-growing area of clinical practice.

PMID- 15493245
TI  - Employment self-disclosure of postsecondary graduates with learning disabilities:
      rates and rationales.
AB  - One hundred thirty-two graduates with learning disabilities (LD) of a large,
      public, competitive postsecondary institution were surveyed to determine if they
      had self-disclosed their LD to their current employer and to provide the reasons
      for choosing to self-disclose or not to self-disclose. Based on a response rate
      of 67.4% (n = 89), the results indicated that 86.5% of the respondents were
      employed full time. Although nearly 90% of the respondents stated that their LD
      affected their work in some way, only 30.3% self-disclosed to their employer. Of
      those who had not self-disclosed, the majority reported that there was no reason
      or need to self-disclose. However, 46.1% reported not self-disclosing due to fear
      of a potentially negative impact in the workplace or due to a concern for job
      security. Specific rationales for disclosure and information related to the use
      of self-reported accommodations and strategies are presented.

PMID- 15493246
TI  - The accuracy of academic self-evaluations in adolescents with learning
      disabilities.
AB  - The purpose of this study was to document the degree of overestimation of
      academic skills among students with learning disabilities (LD) and to evaluate
      the role of reference group and metacognitive awareness in such overestimation.
      High school students with (n = 52) and without (n = 49) LD in Grades 9 through 12
      completed a self-concept scale and a survey requiring them to rate their own
      academic skills in 17 specific skill areas. Students were further asked to
      predict their performance on two academic tasks prior to actually performing the
      tasks. The students' mothers or fathers, their English teachers or academic
      advisors, and (in the case of the students with LD) their special education case
      managers also completed the skill rating inventory and predicted student
      performance on the two tests. Despite reporting significantly lower academic self
      concepts, students with LD overestimated their academic skills relative to the
      ratings of others and to their actual test performance. Such overestimation was
      less pronounced among the students without LD. All participants reported using
      similar reference groups in making their judgments. Analyses of item-by-item
      accuracy judgments from the two tests revealed evidence of group differences in
      metacognitive awareness that may be related to the overestimation. These findings
      have implications for realistic goal setting and effective self-advocacy.

PMID- 15493247
TI  - Students classified as LD who received course substitutions for the college
      foreign language requirement: a replication study.
AB  - This replication study examined whether 158 college students classified as
      learning disabled (LD) who were granted course substitutions for the foreign
      language (FL) requirement would display significant cognitive and academic
      achievement differences when grouped by levels of IQ-achievement and achievement
      achievement discrepancy and by level of performance on an FL aptitude test
      (Modern Language Aptitude Test; MLAT), phonological/orthographic processing
      measures, and in FL courses. The results showed that there were few differences
      among groups with differing levels of IQ-achievement or achievement-achievement
      discrepancy (i.e., < 1.0 SD, 1.0-1.49 SD, and > 1.50 SD) on MLAT and American
      College Testing (ACT) scores, graduating grade point average (GPA), or college FL
      GPA. The results also showed that between groups who scored at or above versus
      below the 15th percentile (i.e., < 1.0 SD) on the MLAT, there were no differences
      on measures of graduating GPA, college FL GPA, native language skill, ACT score,
      and Verbal IQ. Demographic findings showed that 44% of these petition students
      met a minimum IQ-achievement discrepancy criterion (> or = 1.0 SD) for
      classification as LD. These findings suggest that many traditional assumptions
      about LD and FL learning are likely to be false.

PMID- 15493248
TI  - One size still does not fit all in specific learning disability assessment across
      ethnic groups.
AB  - The use of IQ scores and discrepancy formulas for identifying specific learning
      disabilities (SLD) has been widely discredited by prominent researchers for more
      than a decade. Nevertheless, the overwhelming majority of state policies still
      specify the use of discrepancy formulas, including the simple difference method,
      which is psychometrically inferior to regression-based methods. This study
      compares the use of a minimum IQ cutoff score and a simple difference method
      versus a regression-based method for identifying SLD in a sample of African
      American and European American full-time college students (N = 117). Replicating
      the findings from previous studies using typically achieving children, typically
      achieving adults, and school-age children with SLD, this study adds to the chorus
      of voices criticizing the use of outdated assessment practices that can have
      deleterious effects for individuals with SLD. The implications for legislative
      policy are discussed in the context of the historical overrepresentation of
      African Americans in all special education categories except SLD and the
      increased access to higher education that students with SLD have gained during
      the past decade.

PMID- 15493249
TI  - The role of speed of processing, rapid naming, and phonological awareness in
      reading achievement.
AB  - This study investigated the role of speed of processing, rapid naming, and
      phonological awareness in reading achievement. Measures of response time in
      motor, visual, lexical, grammatical, and phonological tasks were administered to
      279 children in third grade. Measures of rapid object naming, phonological
      awareness, and reading achievement were given in second and fourth grades.
      Reading group comparisons indicated that poor readers were proportionally slower
      than good readers across response time measures and on the rapid object naming
      task. These results suggest that some poor readers have a general deficit in
      speed of processing and that their problems in rapid object naming are in part a
      reflection of this deficit. Hierarchical regression analyses further showed that
      when considered along with IQ and phonological awareness, speed of processing
      explained unique variance in reading achievement. This finding suggests that a
      speed of processing deficit may be an "extraphonological" factor in some reading
      disabilities.

PMID- 15493250
TI  - Psychometric stability of nationally normed and experimental decoding and related
      measures in children with reading disability.
AB  - Achievement and cognitive tests are used extensively in the diagnosis and
      educational placement of children with reading disabilities (RD). Moreover,
      research on scholastic interventions often requires repeat testing and
      information on practice effects. Little is known, however, about the test-retest
      and other psychometric properties of many commonly used measures within the
      beginning reader population, nor are these nationally normed or experimental
      measures comparatively evaluated. This study examined the test-retest
      reliability, practice effects, and relations among a number of nationally normed
      measures of word identification and spelling and experimental measures of
      achievement and reading-related cognitive processing tests in young children with
      significant RD. Reliability was adequate for most tests, although lower than
      might be ideal on a few measures when there was a lengthy test-retest interval or
      with the reduced behavioral variability that can be seen in groups of beginning
      readers. Practice effects were minimal. There were strong relations between
      nationally normed measures of decoding and spelling and their experimental
      counterparts and with most measures of reading-related cognitive processes. The
      implications for the use of such tests in treatment studies that focus on
      beginning readers are discussed.

PMID- 15493251
TI  - Temporal resolution of auditory perception and verbal working memory in 15
      children with language impairment.
AB  - We investigated temporal resolution of auditory perception (TRAP), verbal working
      memory, and speech perception in 15 children with language impairment (LI) in
      comparison with a control group of 99 typical children. A computerized two-choice
      test was used to assess these three abilities. No deficits in TRAP were found in
      the LI group, and the thresholds were similar for both study groups. It was
      interesting that the variability was high for both groups and that the control
      group's performance was poorer than reported in some previously published
      studies. There were significant differences in the two groups' performance on
      speech perception and verbal working memory. Working memory was the most
      sensitive of these two measures.

PMID- 15493252
TI  - Effectiveness of a school-based multicomponent program for the treatment of
      children with ADHD.
AB  - The objective of this study was to evaluate the efficacy of a multicomponent
      program for treating attention-deficit/hyperactivity disorder (ADHD) carried out
      by teachers in a classroom context. Dependent measures included
      neuropsychological tasks, behavioral rating scales for parents and teachers,
      direct observation of behavior in the classroom, and academic records of children
      with ADHD. Fifty children with ADHD participated in the study. The teachers of 29
      of the 50 students were trained in the use of behavior modification techniques,
      cognitive behavior strategies, and instructional management strategies. The other
      21 students formed the control group. Parents' and teachers'ratings detected
      improvements in primary symptoms (inattention-disorganization, hyperactivity
      impulsivity) and in behavioral difficulties usually associated with ADHD (e.g.,
      antisocial behavior, psychopathological disorders, anxiety). Furthermore, the
      results showed increased academic scores, enhanced classroom behavioral
      observations, and improved teachers' knowledge about the strategies directed
      toward responding to the children's educational needs.

PMID- 15493253
TI  - Mathematical problem-solving profiles of students with mathematics disabilities
      with and without comorbid reading disabilities.
AB  - The purpose of this study was to describe the mathematical problem-solving
      profiles of students with mathematics disabilities (MD) with and without comorbid
      reading disabilities (RD). The disability status of fourth-grade students was
      verified through testing (n = 18 MD; n = 22 MD + RD). Then a hierarchy of
      mathematics problem-solving tasks was administered. The results demonstrated
      large deficits for both groups; however, the differences between students with MD
      and those with MD + RD were mediated by the level of problem solving (arithmetic
      story problems vs. complex story problems vs. real-world problem solving) and by
      performance dimension (operations vs. problem solving). On arithmetic story
      problems, the differences between the disability subtypes were similar for
      operations and problem solving. By contrast, on complex story problems and real
      world problem solving, the differences between the subtypes were larger for
      problem solving than for operations.

PMID- 15493254
TI  - Immune network theory: a role for parallel distributed processing?

PMID- 15493255
TI  - Herpes simplex type 1-induced Fc receptor binds to the Cgamma2-Cgamma3 interface
      region of IgG in the area that binds staphylococcal protein A.
AB  - The binding site of immunoglobulin G (IgG) to herpes simplex virus (HSV) type 1
      induced Fc receptor was investigated using human IgG Fc intermediate (Fc(i))
      fragments, fragment D of staphylococcal protein A (SPA) and chemically modified
      human IgG. Human IgG Fc(i) fragment composed of one Cgamma2 and two Cgamma3
      domains, bound strongly to HSV-1-infected cells. Fragment D, a monovalent subunit
      of SPA, inhibited the binding of radiolabelled human IgG Fc fragments to the HSV
      Fc receptor. Reductively methylated human IgG reacted equally well to HSV
      infected cells, as did chemically unmodified IgG in contrast to N-acetylimidazole
      modified and diethylpyrocarbonate-modifed human IgG, which were unreactive. These
      results suggest a similar binding site on human IgG for SPA and the HSV-1 Fc
      receptor with involvement of the amino acid residues Tyr and His but not Lys. The
      similarities of binding sites on the IgG molecule for the HSV-1 Fc receptor and
      rheumatoid factors (RF) may be important for understanding the mechanism of RF
      production in rheumatoid arthritis or other disease states.

PMID- 15493256
TI  - Functional cross-reactivity between the glycoprotein B of herpes simplex virus
      type 1 and Epstein-Barr virus.
AB  - A monoclonal antibody (T157) directed against gB-1, the glycoprotein B (gB) of
      herpes simplex virus-1 (HSV-1) shows positive indirect immunoflourescent staining
      with an Epstein-Barr virus (EBV)-transformed lymphoblastoid cell line B95-8. SDS
      PAGE and Western blot analysis show that B95-8 cells contain a 110,000 MW protein
      that co-migrates with the 110,000-115,000 MW gB-1. The gB-1 homologue of EBV (gB
      EBV), immunopurified using a T157 affinity column, cross-stimulates HSV-1 immune
      T cells to proliferate in vitro. Mice immunized by a single subcutaneous
      injection of 30 microg gB-EBV in saline developed significant protection against
      HSV-1 challenge infection. Therefore gB-EBV can be considered a potential
      candidate vaccine and as an antigen to examine the cell-mediated immune response
      mounted by the host to limit virus spread during productive infection. The
      significance of a better understanding of the immune response to this and other
      EBV proteins of productive infection as an alternative to limit tumour growth by
      preventing virus spread is discussed.

PMID- 15493257
TI  - The plasma protein which inhibits complement-mediated prevention of immune
      precipitation is an Fc binding protein.
AB  - A glycoprotein (gp60) that inhibits complement-mediated prevention of immune
      precipitation (PIP) has been purified from normal serum. [125I]gp60 binds to IgG
      but not to IgA or IgM. The binding site has been shown to be localized on the Fc
      piece. The binding of radiolabelled gp60 to IgG has been analysed by direct
      binding and Scatchard, double-reciprocal and Hill plots. The mean affinity
      constant of gp60 for IgG is 1.56 x 10(8) l/mol and there appears to be a single
      class of binding sites for gp60 on IgG. Saturation was achieved when one molecule
      of gp60 was bound to each molecule of IgG. In competition inhibition assays, gp60
      was shown to compete with C1q and IgM and IgG rheumatoid factors. The ability to
      inhibit C1q binding suggests that gp60 inhibits PIP by preventing binding and
      activation of C1. The possibility that gp60 is a fluid-phase Fc gamma receptor is
      discussed. See also the note added in proof.

PMID- 15493258
TI  - Regulation of serum antibodies induced in syngeneic rats after administration of
      monoclonal antibody MT10:21.
AB  - Monoclonal antibody (mAb) MT10:21, a rat IgG2a, reacts with antigens expressed on
      the metastatic subclone MTLn3 of the 13762NF rat mammary adrenocarcinoma (North,
      Steck & Nicolson, 1986). The clearance of mAb MT10:21 from circulation was
      monitored 15 days after s.c. injection of MTLn3 tumour cells into the mammary fat
      pad of syngeneic rats. At this point, when tumour-burden was small (< 1 cm
      average diameter), mAb MT10:21 was injected i.v. and serum samples were taken
      over the 7 days following injection. It was observed that when mAb MT10:21 was
      injected i.v. into syngeneic rats it induced a humoral immune response. Four days
      after injection of mAb, IgM serum antibodies which bound to the MTLn3 cell line
      were detected in both tumour and non-tumour bearing rats. Using a binding assay,
      tumour-bearer sera showed a steady increase in MTLn3-reactive antibodies over the
      7-day assay period. These MTLn3-reactive antibodies were detectable in non-tumour
      bearer sera, but reactivity was not as pronounced. Tumour-bearing rats also had
      serum IgM antibodies which bound to mAb MT10:21 in vitro, but not to a non
      specific, isotype-identical control mAb, MC9:13. These serum antibodies were able
      to partially inhibit (up to 47%) the binding of 125I-labelled mAb MT10:21 to
      MTLn3 cells. This anti-idiotypic immune response was not observed in the non
      tumour bearers. When the tumour was allowed to grow for a period of 30 days in
      vivo (average tumour diameter 2 cm), these serum antibodies were not readily
      detectable, suggesting that tumour burden had a significant effect on suppressing
      the humoral immune responsiveness of these tumour-bearing rats. In a standard
      delayed-type hypersensitivity (DTH) assay specific immunity to mAb MT10:21 was
      induced in vivo.

PMID- 15493259
TI  - Interleukin-5 induces maturation but not class switching of surface IgA-positive
      B cells into IgA-secreting cells.
AB  - There is a body of evidence suggesting that IgA production is regulated by helper
      T cells or their products. To elucidate molecular mechanisms of IgA production,
      the role of lymphokines in the in vitro antigen-specific and polyclonal IgA
      responses was examined. Supernatants from antigen-stimulated T cells or mitogen
      stimulated T-cell clones can enhance 2,4-dinitro phenyl (DNP)-specific IgM, IgG1
      and IgA production in cultures of DNP-ovalbumin (OVA)-stimulated T-cell-depleted
      spleen cells from DNP-keyhole limpet haemocyanin-primed mice. The IgA enhancement
      was inhibited by anti-IL-5 monoclonal antibody. Purified recombinant IL-5 could
      also enhance anti-DNP IgA production in a dose-dependent manner. This enhancing
      effect was not substituted by IL-1, IL-2, IL-3 or IL-4. Polyclonal IgA secretion
      of lipopolysaccharide-stimulated normal B cells was augmented preferentially by
      IL-5, but not by IL-4. Surface IgA-positive (sIgA+) B cells, but not surface IgA
      negative B cells, responded to IL-5 for the development of IgA-secreting cells.
      Limiting-dilution analysis revealed that IL-5 increases the frequency of IgA
      secreting cells in sIgA+ B-cell populations. These results indicate that IL-5
      plays an essential role in the antigen-specific and polyclonal IgA formation as a
      maturation-inducing factor rather than class-switching factor.

PMID- 15493260
TI  - The T-cell response to haptenated insulins. I. The proliferative response.
AB  - Mice were primed with TNP-derivatized insulin, or TNP-Mycobacteria, and lymph
      node cells were challenged in vitro with haptenated and unhaptenated antigens.
      Using either priming antigen, T-cell proliferative responses could be obtained to
      TNP-insulin. In B10 (H-2b), mice, which are responders to beef insulin (BI), but
      not to pork insulin (PI), TNP-BI or TNP-PI primed a response to TNP beef and TNP
      pork insulins, and to beef but not pork insulin, suggesting that a proportion of
      the response was directed to the modified portion of the molecule. However,
      priming with BI resulted in responsiveness to TNP-PI, but not to PI. Also, TNP-BI
      stimulated an augmented proliferative response in BI-primed mice. These results
      suggest that TNP modification can alter the antigenicity of the carrier molecule,
      perhaps by enhancing weak interactions with MHC molecules on presenting cells.
      Finally, there was no evidence that the TNP-dependent response to TNP-pork
      insulin was down-regulated by suppressor cells directed at the carrier molecule.

PMID- 15493261
TI  - The T-cell response to haptenated insulins. II. The antibody response.
AB  - As described in an accompanying paper, trinitrophenyl (TNP) modification of pork
      insulin (PI) at the A1 glycine position allows this molecule to stimulate a
      proliferative response in H-2b (B10) mice. We now show that this antigen
      stimulates low IgG responses in the same strain of mice. Our results show that T
      cell help and proliferation may therefore be regulated independently.

PMID- 15493262
TI  - Maximal interferon-gamma production and early synthesis of interleukin-2 by CD4+
      CDw29- CD45R- p80- human T lymphocytes.
AB  - Functionally distinct subsets within the T-helper (CD4+) cell population have
      been described in man, rat and mouse. We have shown previously that the CD4+ 45R-
      human lymphocytes are producers of IL-2 within 24 hr of polyclonal stimulation
      and are the major interferon (IFN) producers. The mAbs 4B4 (CDw29) and Leu 8
      (p80) are here used together with Leu-18 (CD45R) to characterize the
      subpopulations of the CD4+ human lymphocytes in more detail. The majority of the
      CD45R+ cells were CDw29- and the majority of the CDw29+ cells were CD45R-. Most
      of the CD45R+ cells (78%) were also p80+. A significant number of cells (12%)
      were CDw29- CD45R-. The predominant subpopulations were defined to be CDw29-
      CD45R+ p80+ (31%), CDw29+ CD45R- p80- (24%) and CDW29+ CD45R- p80+ (18%). Within
      the CD4+ CD45R- subpopulation different subsets vary in their capacities to
      produce IFN and to produce IL-2 within 24 hr after activation. CD4+ CDw29- CD45R-
      p80- T lymphocytes produced the largest quantities of IFN and IL-2.

PMID- 15493263
TI  - Phorbol myristate acetate and calcium ionophore A23187-stimulated human T cells
      do not express high-affinity IL-2 receptors.
AB  - Phorbol myristate acetage (PMA) and Ca2+ ionophore A23187 mimic early signal
      transduction pathways and activate purified human T cells to secrete large
      quantities of interleukin-2 (IL-2) and to proliferate. Despite producing 50-100
      fold more IL-2 than phytohaemagglutinin (PHA)-activated peripheral blood
      lymphocytes (PBL), PMA/A23187-stimulated human T cells proliferate less than
      cells activated by PHA. Washing the cells to remove PMA/A23187 was found to
      increase cellular proliferation two to five-fold. High-affinity IL-2R (HA-IL-2R)
      were found to be expressed by human T cells that had been washed 24 hr after
      PMA/A23187 stimulation and recultured without stimulus for an additional 48 hr,
      but not by T cells constantly exposed to PMA/A23187 for 72 hr. Radioligand
      binding studies with [125I]IL-2 demonstrated that while the alpha (p55) and beta
      (p70-75) subunits of HA-IL-2R were both present on the constant PMA/A23187
      stimulated T cells, they did not appear to associate to form functional HA-IL-2R.
      This defect in the expression of bio-active HA-IL-2R on constant PMA/A23187
      stimulated human T cells seems to account for their low proliferative response.

PMID- 15493264
TI  - Impaired non-specific suppressor-inducer T-cell activity in aged murine Peyer's
      patches, which can be corrected largely by IL-2 in vitro.
AB  - To shed further light on the mechanism of age-associated T-cell-mediated
      immunoregulatory alterations in gut non-specific mucosal immune responses, we
      studied in vitro the function of a variety of concanavalin A (Con A)-activated
      immunoregulatory T-cell subsets derived from aged murine Peyer's patches (PP)
      (BALB/c > 24 months old) in the production of class-specific immunoglobulins (Ig)
      by young (5-8 months old) lipopolysaccharide (LPS)-activated PP B cells. The in
      vitro induction of Con A-activated PP helper (Th) [L3T4+ Lyt-2- Vicia villosa non
      adherent (VV-)], suppressor (Ts) L3T4- Lyt-2+ (VV-), and contrasuppresor (Tcs)
      (L3T4+ Lyt-2- VV+) T cells were compared for the two age groups. The activities
      of aged PP-derived Ts and Tcs cells were greatly impaired, in contrast to minor
      defects in activity of the aged Th cells. The induction of effector Tcs cells,
      however, depended on the presence of functionally effective Ts cells. Recombinant
      IL-2 (rIL-2) could largely correct this impaired generation of aged Ts and Tcs
      cells. Next, we determined the activities of Ts inducer (Tsi) (L3T4+ Lyt-2- VV-)
      T cells in aged PP in vitro. The cell activity was considerably diminished in
      aged mice. Then, we tested in vitro whether rIL-2 could reconstitute the impaired
      generation of the aged non-specific Tsi cell. The function of the latter cell was
      largely restored by rIL-2. Thus, the major functional (intrinsic) defect present
      in immunocompetent T lymphocytes of murine aged PP was confined to the Tsi cell.

PMID- 15493265
TI  - Recirculation of lymphocyte subsets (CD5+, CD4+, CD8+, SBU-T19+ and B cells)
      through gut and peripheral lymph nodes.
AB  - The surface phenotypes (CD5+, CD4+, CD8+, SBU-T19+, MHC class II+, T80+ and sIg+)
      of lymphocytes in blood, and in prescapular and ileocaecal efferent lymph of
      sheep, have been determined. The similarity in the distribution of lymphocyte
      subsets in both lymph compartments indicated that the non-random migration of
      lymphocyte populations to peripheral lymph nodes and gut could not be due to
      preferential migration of a particular lymphocyte subset such as CD4+ or CD8+
      cells to one tissue. Marked differences in the percentage of lymphocyte subsets
      between blood and efferent lymph suggested that some lymphocyte subsets leave the
      blood with differing efficiencies and that differential extraction of lymphocyte
      subsets from blood by a lymph node may be due to subset-specific lymphocyte
      endothelial interactions.

PMID- 15493266
TI  - Murine T-cell clones against Entamoeba histolytica: in vivo and in vitro
      characterization.
AB  - Eleven T-cell clones were raised from the spleens of BALB/c mice hyperimmunized
      against a crude soluble extract of Entamoeba histolytica trophozoites. Seven
      clones were of the Lyt-1+, and four of the Lyt-23+ phenotype. All clones
      proliferated in the presence of E. histolytica antigens but not to a purified
      protein derivative; five clones proliferated to a crude extract of the E.
      histolytica-like Laredo amoebae. Ten clones secreted T-cell growth factors in
      response to E. histolytica antigens. Two clones (Lyt-23+) mediated direct
      lymphocytotoxicity (73% and 86%) against amoebic trophozoites that was inhibited
      with rabbit anti-mouse TNF-alpha. Supernatants of five of the clones (all Lyt-1+)
      activated mouse peritoneal macrophages (Mphi) to kill E. histolytica trophozoites
      in vitro, seemingly independent of secreted reactive oxygen intermediates (O2-
      and H2O2) in the case of three clones supernatants. All of the clones that were
      activating Mphi to kill amoeba in vitro also mediated a local DTH reaction in
      mouse footpad. Our results demonstrate direct lymphocyte cytotoxicity via a
      cytolytic molecule antigenically related to TNF-alpha and lymphokines activating
      Mphi for amoebic killing by oxidative and non-oxidative mechanisms, the latter
      process mediated by a macrophage-activating factor (MAF) distinct from interferon
      gamma (IFN-gamma).

PMID- 15493267
TI  - The phenotypic and molecular characterization of Nb2 lymphoma cells activated
      with IL-2 and human growth hormone.
AB  - The Nb2 rat lymphoma cell line has the unique property that its growth is
      dependent on lactogenic pituitary hormones. Cell surface staining with monoclonal
      antibodies showed expression of class I MHC alloantigens of the RT1u haplotype,
      but no expression of class II MHC antigens. Staining for differentiation markers
      was strongly positive with antibodies OX52, W3/13 and OX44. Partial and weaker
      staining was obtained with CD2, P4/16 and the transferrin receptor. Nb2 cells
      were negative with CD5, OX40 and CD4, whilst CD8 stained only a minor fraction
      (1%) and certain variant clones of the cell line. This general pattern of
      staining is consistent with the phenotype of a small subpopulation of immature T
      cells. Nb2 cells proliferated in response to recombinant human IL-2, although
      they did not stain with antibodies against the IL-2 receptor. Enhancement of the
      stimulation by IL-2 in the presence of a submitogenic concentration of hGH
      indicated a synergism between these two hormones, and responses were suppressed
      by a similar dose of cyclosporin A (ID50=2 microg/ml). Although IL-2 could not be
      identified in culture supernatants, the presence of mRNA for IL-2, IL-2R and IL-4
      was demonstrated by dot blot analysis. Finally, evidence that the Nb2 lymphoma is
      of T-cell lineage was given by Northern blot detection of mRNA for the alpha and
      beta chains of the T-cell receptor.

PMID- 15493268
TI  - Expression of CD6 and the UCHL1-defined CD45 (p180) antigen by human colonic T
      lymphocytes.
AB  - Cryostat sections of histologically normal human colon were studied by double
      label immunofluorescence techniques using a panel of monoclonal antibodies to T
      lineage antigens and activation markers, with particular reference to the CD6
      antigen. In the lamina propria, the majority population of T cells was of the
      CD3+, CD6+, CD4+ subset, of which virtually all were of the UCHL1+, CD45R-, Leu 8
      phenotype of antigen-committed helper T cells. This majority lamina propria
      population did not express markers associated with blastogenesis (CD7),
      activation (MHC class II, CD25, CD38) or proliferation (OKT9, Ki67). In both
      intra-epithelial and lamina propria compartments, a subpopulation of CD3+ T cells
      was identified which did not express either the CD6 or CD5 peripheral 'pan T'
      markers. Most of the CD3+, CD6- cells were of the CD8+ (cytotoxic-suppressor)
      subset which co-expressed the CD7 antigen with a much higher frequency than did
      the CD6+ subpopulation. Expression of CD25, CD38 and HLA-D antigens, although
      infrequent, was confined to this CD8+, CD5-, CD6- population. Our data thus imply
      that the colonic mucosa is largely populated by mature, antigen-committed resting
      T cells of the helper-inducer phenotype.

PMID- 15493269
TI  - Dendritic cells and T cells transfer sensitization for delayed-type
      hypersensitivity after skin painting with contact sensitizer.
AB  - The cells involved in the development of delayed-type hypersensitivity (DTH) to
      the contact sensitizer fluorescein isothiocyanate (FITC) were examined. Cells
      used for transferring sensitization were obtained from donor mice up to 5 days
      following skin painting with FITC. Recipient mice were sensitized by footpad
      injections of dendritic cells (DC) obtained from donor lymph nodes up to 3 days
      following skin painting, when DC expressed high levels of antigen. DTH, assessed
      by ear swelling 24 hr following ear challenge with FITC, was detected when
      recipient mice were challenged 5 days after transfer of DC, but not when ear
      challenged immediately after transfer. Removal of donor DC using the cytotoxic
      antibody 33D1, plus complement, either from the DC-enriched population or from
      whole lymph node cells 24 hr after skin painting, abolished the capacity to
      transfer DTH. Purified T lymphocytes obtained from donor mice between Days 3 and
      5 after skin painting, transferred DTH when recipients were ear challenged with
      FITC 5 days after footpad injections. DTH also occurred in mice ear challenged
      with antigen immediately after receiving footpad injections of either normal or
      irradiated T cells obtained from donors 4 days after skin painting. B cells and
      macrophages did not transfer sensitization for DTH throughout the time-course.
      Therefore an early stage in the immune response, where antigen-bearing DC
      initiated DTH, was distinguished from a later stage, where T cells transferred
      sensitization.

PMID- 15493270
TI  - MHC class II antigen expression is not induced on murine epidermal keratinocytes
      by interferon-gamma alone or in combination with tumour necrosis factor-alpha.
AB  - Epidermal keratinocytes are induced to express MHC class II molecules in a
      variety of disease states associated with immune activity. To investigate the
      mechanism of this process we have exposed murine and rat keratinocytes to a
      variety of lymphokines and monitored changes in their MHC molecule expression.
      Murine cultured keratinocytes were treated with recombinant interferon-gamma (IFN
      gamma), and MHC antigen expression quantified by flow cytometry. IFN pretreatment
      resulted in the up-regulation of class I molecule expression, but no class II
      expression was detected. In addition, cultured murine keratinocytes exposed to a
      combination of recombinant tumour necrosis factor (TNF)-alpha and IFN-gamma, or
      crude lymphocyte supernatants, failed to show positive membrane staining for
      class II molecules. However, rat keratinocytes cultured under conditions
      identical to murine cells were induced to express class II molecules after IFN
      gamma pretreatment. The inability of IFN to induce class II expression on murine
      keratinocytes appears not to result from cell culture, as subcutaneous injection
      of IFN fails to induce epidermal class II antigen expression. However, class II
      expression can be induced on rat epidermis in vivo. Thus, the response of
      epidermal keratinocytes to IFN-gamma appears to show species variation.

PMID- 15493271
TI  - Abnormalities in the SJL mouse provide evidence for different mechanisms for the
      induction and transfer of tolerance to mouse thyroglobulin.
AB  - Experimental autoimmune thyroiditis (EAT) induced by immunization of susceptible
      (H-2k) mice can be significantly suppressed by pretreatment with soluble mouse
      thyroglobulin administered intravenously. Lightly irradiated recipients of spleen
      cells from donors pretreated in this way show a reduced response when
      subsequently challenged with mouse thyroglobulin and adjuvant (Kong et al., 1982;
      Parish et al., 1988). Previous studies on the SJL mouse revealed, among other
      abnormalities, a lack of suppressor cells (Cooke & Hutchings, 1984; Hutchings,
      Varey & Cooke, 1986; Amagai & Cinader, 1981) and therefore tolerance induction to
      mouse thyroglobulin and subsequent transfer was examined in these animals. The
      SJL mouse could be tolerized by i.v. administration of mouse thyroglobulin, but
      transfer of spleen cells from these animals failed to mediate suppression in
      syngeneic recipients. Several congenic strains of B10 mice showed similar 'in
      situ' tolerance without subsequent successful transfer and we conclude that the
      tolerance system described may be mediated by two distinct pathways and that the
      SJL appears to be defective only in the second pathway. Studies on other mouse
      strains suggest that the ability to be tolerized or to transfer tolerance is not
      dependent on a particular H-2 or I-E.

PMID- 15493272
TI  - Mechanisms of lymphocyte adhesion to endothelial cells: studies using a LFA-1
      deficient cell line.
AB  - In order to investigate the role of lymphocyte function-associated antigen 1 (LFA
      1) in lymphocyte adhesion to endothelial cells (EC), we have studied the adhesion
      of a LFA-1-deficient lymphoblastoid cell line, ICH-KM, which has < 10% of the
      cell surface LFA-1 expressed on a normal lymphoblastoid cell line, ICH-BJ. The
      adhesion of ICH-KM cells to unstimulated EC was 49.9 +/- 8.6% (mean +/- SD) that
      of ICH-BJ cells. Moreover, phorbol ester-stimulated ICH-KM cells showed a
      considerably weaker increase in adhesion to unstimulated EC compared with ICH-BJ
      cells (mean +/- SD increase in percentage adhesion, 3.8 +/- 2.3 compared with
      18.5 +/- 8.0; P<0.025). In contrast, there was no significant difference between
      the enhanced adhesion of ICH-KM cells and ICH-BJ cells to interleukin-1 (IL-1)
      stimulated EC. Thus ICH-KM cells showed a 22.7 +/- 11.0 (mean +/- SD) increase in
      percentage adhesion to IL-1-stimulated EC compared with the 24.8 +/- 8.5 increase
      in percentage adhesion of ICH-BJ cells. Anti-LFA-1 monoclonal antibodies had no
      effect on the enhanced adhesion of ICH-KM and ICH-BJ cells to IL-1-stimulated EC
      but abolished the differences in adhesion between the two cell lines. The study
      therefore indicates that although a major part of unstimulated and phorbol ester
      stimulated lymphocyte-EC adhesion is dependent upon LFA-1, the enhanced adhesion
      due to stimulation of EC with IL-1 is not dependent upon this molecule. The data
      therefore supports the existence of cytokine-inducible LFA-1-independent adhesion
      molecules for lymphocytes on EC.

PMID- 15493273
TI  - Interleukin-2 modulates the expression of lymphocyte function-associated antigen
      one (LFA-1) and p150,95 during the generation of lymphokine-activated killer
      (LAK) cells.
AB  - Lymphocyte function-associated antigen-one (LFA-1), Mac1 and p150,95 represent a
      family of heterodimeric cell surface molecules with a common beta subunit and
      distinct alpha subunits. LFA-1 is known to be functionally important in cell-cell
      interactions between immune cells. In the present study, a mouse monoclonal
      antibody (mAb), RH1-38, which recognizes an epitope on the beta-chain of LFA-1
      was used to study the function and expression of LFA-1 on lymphokine-activated
      killer (LAK) cells. This mAb has been shown previously to block, in the absence
      of complement, cytolytic activity mediated by natural killer (NK) cells,
      cytotoxic T lymphocytes (CTL), and a monocyte-like cell (phorbol diester
      stimulated HL-60 cells). LAK cells were generated by culturing in vitro human
      peripheral blood lymphocytes (PBL) in the presence of human recombinant
      interleukin-2 (rIL-2), and cytotoxic activity was measured by a 51Cr-release
      assay using the human NK-resistant Daudi cell line. Addition of RH1-38 ascites
      supernatant, purified RH1-38 mAb, or F(ab')2 fragment of RH1-38 markedly reduced
      (>80) LAK cytolytic activity, whereas NS-1 (parent hybridoma) ascites
      supernatant, normal mouse IgG, and monoclonal anti-HLA had no effect on LAK
      mediated killing. Equivalent inhibition of NK and CTL activity by purified RH1-38
      required 10-100-fold more antibody. Appreciable inhibition occurred if the mAb
      was added up to 2 hr after LAK cells were mixed with targets. Indirect
      immunofluorescence flow cytometry and immunoprecipitation studies revealed that
      LFA-1 and p150,95 expression were dramatically enhanced in PBL populations
      cultured with rIL-2 compared with PBL cultured without rIL-2; Daudi cells
      expressed no detectable LFA-1 family heterodimers. Time-course experiments
      demonstrated that during culture of PBL in the presence of rIL-2, development of
      enhanced expression of LFA-1 and p150,95 correlated closely with LAK cytolytic
      activity. These studies (i) demonstrate that LFA-1 and/or p150,95 are
      functionally important effector cell surface molecules expressed by LAK cells and
      that some homology to NK and CTL mechanisms of cell-mediated lysis may exist; and
      (ii) suggest that enhanced LFA-1 and/or p150,95 expression are important for
      development of the fully differentiated LAK effector cell in the presence of rIL
      2.

PMID- 15493274
TI  - Immunological studies of NK cell-deficient beige mice. I. Defective ability of
      beige lymphocytes to mediate local and systemic graft-versus-host reactions.
AB  - We have examined the role of donor natural killer (NK) cells in various forms of
      local and systemic graft-versus-host reaction (GvHR), by using beige mouse
      lymphocytes as the donor cell population. In contrast to lymphocytes from normal,
      congenic C57Bl/6 (B6) mice, beige spleen cells could not induce either an acute,
      lethal GvHR or a proliferative form of GvHR in adult, unirradiated F, hybrid
      hosts. In addition, beige donor cells produced little GvHR in the popliteal lymph
      node after local transfer and caused less severe and less sustained intestinal
      GvHR in unirradiated hosts. However, beige cells were fully capable of inducing a
      lethal GvHR in irradiated hosts. These studies indicate that beige mice have a
      defective ability to induce many types of GvHR, but suggest that this is a
      quantitative abnormality rather than an absolute lack of responsive cells. We
      propose that this may reflect a defect in T-cell function rather than a pure NK
      cell defect.

PMID- 15493275
TI  - Immunological studies of NK cell-deficient beige mice. II. Analysis of T
      lymphocyte functions in beige mice.
AB  - Lymphocytes from natural killer (NK) cell-deficient beige mice have a poor
      ability to induce many different forms of graft-versus-host reaction (GvHR). In
      this study, we have examined whether this defect could reflect an associated
      abnormality in beige T-lymphocyte function. Compared with normal, congenic
      C57Bl/6 (B6) mice, beige mice had similar numbers and proportions of T-cell
      subsets and generated normal allospecific delayed-type hypersensitivity (DTH)
      responses in vivo. In addition, beige mice developed normal or enhanced DTH
      responses to the protein antigen, ovalbumin (OVA), and were fully susceptible to
      the induction of tolerance by feeding OVA. Beige lymphocytes recirculated
      normally in vivo and showed enhanced proliferative responses to mitogens and
      alloantigens in vitro. In contrast, beige responder cells generated poor
      cytotoxic T-lymphocyte (CTL) responses in vitro and had quantitatively identical
      defects in CTL and NK cell activation after alloimmunization in vivo. These
      results suggest that although many effector and regulatory T-cell functions are
      normal in beige mice, the NK-cell defect in these animals is paralleled by
      impaired CTL activity. We suggest that abnormal T-cell function accounts for the
      inability of beige lymphocytes to induce GvHR.

PMID- 15493276
TI  - The effect of experimental haemocarbofiltration upon activity of mononuclear
      cells from normal and autoimmune patients.
AB  - We examined the functional activity of peripheral blood mononuclears (PBM) of 18
      healthy subjects, 18 patients with pemphigus vulgaris, 12 with bullous pemphigoid
      and nine with discoid lupus erythematosus, after haemofiltration on carbon haemo
      adsorbents of 'SKN' type. Proliferation in the response to PHA and Con A, for IL
      1 and IL-2 production, and exogenous IL-2 absorption were assayed. The presence
      of IL-1 and IL-2 inhibitors in haemocarbo-adsorbent eluants was shown. We also
      investigated the natural killer (NK) and antibody-dependent cellular cytotoxic
      (ADCC) activities. We found significant increases of both lectin-dependent
      proliferation and of interleukin production by PBM of autoimmune patients after
      two to four perfusions. The ability of PBM to absorb IL-2 displayed a steady
      growth after each perfusion, whereas increase of NK and ADCC activities was
      observed after not less than six passes. The enhancement of PBM functional
      activity in autoimmune patients was accompanied by accumulation of IL-1 and IL-2
      inhibitors in the sorbent. It was concluded that therapeutic effects of
      haemofiltration in autoimmune diseases involve improvement of immunocompetent
      cell function due to their deligandization by activated charcoal.

PMID- 15493277
TI  - The interaction of ruminant IgG with receptor type II for IgG on human
      phagocytes.
AB  - The interaction of ruminant IgG with human phagocytes was assessed using Fc
      receptor (FcR)-mediated ingestion and the triggering of a respiratory burst as
      effector functions indicative of receptor-specific interaction. In monomeric
      form, ruminant IgG was three to five orders of magnitude less potent than
      homologous IgG in inhibiting FcR-specific phagocytosis by monocytes. However,
      when attached to tanned sheep erythrocytes (Es-T), ruminant IgG was opsonic, as
      it promoted enhanced phagocytosis of Es-T, comparable to ingestion of rabbit IgG
      coated Es. This phagocytosis was inhibitable by high concentrations of human IgG
      in the fluid phase. Moreover, Es-T precoated with ferritin could be opsonized to
      a similar degree by anti-ferritin IgG from rabbit and cow. However, only bovine
      IgG1, but not IgG2, was opsonic. Bovine and goat IgG of some, but not other,
      suppliers were inactive. Similar results were obtained by measuring the
      respiratory burst triggered by heat-aggregated IgG, using a luminol-enhanced
      chemiluminescence assay. Thus, human IgG and ruminant IgG stimulated monocytes
      and, to a lesser extent, polymorphonuclear leucocytes (PMN), to generate CL.
      Depending on the manufacturer, some preparations of bovine and goat IgG were
      inactive, and bovine IgG2 failed to induce CL. These findings prove that certain
      ruminant IgG preparations, including bovine IgG1 interacting weakly with
      homologous PMN and monocytes, do interact with human PMN, monocytes and
      macrophages in a FcR-specific manner when offered in complexed form. Inhibition
      studies suggest that bovine IgG1 interacts mainly with human FcR type II. In
      contrast, bovine IgG2, regarded as cytophilic for homologous PMN, fails to
      interact with human PMN, monocytes and macrophages.

PMID- 15493279
TI  - Nomenclatre Committee, Working Group on Lymphokines.

PMID- 15493278
TI  - Protective efficacy of antigens solubilized from gut membranes of the cattle
      tick, Boophilus microplus.
AB  - Triton X-100, SDS, n-octyl glucoside, and conditions of alkaline pH and high and
      low ionic strength, were used to solubilize membranes prepared from the mid-gut
      of the cattle tick Boophilus microplus. Hereford cattle (Bos taurus) were
      immunized with soluble membrane antigens in saponin, and then challenged twice
      with 20,000 tick larvae, 7 days apart. All soluble extracts, except that
      extracted with high ionic strength buffer, provided significant protection (56
      78%) (P < 0.05) to immunized cattle compared with control cattle. Precipitation
      of the soluble n-octyl glucoside extract did not alter the immunogenicity of this
      vaccine. Where poor responses to membrane vaccines were obtained (< 60%
      protection), booster injections of antigen effected increased protection. The
      experimental cattle were typed for bovine major histocompatibility system class 1
      antigens. The presence of three antigens (MB5, MB14 and MB20) had a significant
      effect on protective immunity induced by the membrane vaccines (P < 0.05).
      Protein profiles of Triton X-100, n-octyl glucoside and low ionic strength buffer
      extracts were compared by high-performance size-exclusion chromatography. Tick
      membranes extracted by either non-ionic detergents or low ionic strength
      solutions provided the best source of protective antigens.

PMID- 15493281
TI  - [Landscape aspects of host-parasite relationships between parasitic arthropods
      and the narrow-skulled vole Microtus gregalis (Rodentia) in Western Siberia].
AB  - Comparative zoogeographic analysis of outcomes accumulated in the course of long
      term investigation the parasitic and free-living arthropods (Acarina:
      Parasitiformes; Insecta: Siphonaptera) associated with three subspecies of the
      narrow-skulled vole (Microtus gregalis gregalis, M. g. major, M. g. eversmanni)
      in various landscape zones and subzones in a flat part of Western Siberia,
      foothills of the Altai-Sayan mountain system and mountains of Southwest Altai.
      The obtained data, on the one hand, recover specific features of certain parasite
      communities that reflect ecological peculiarity of a host species living in
      conditions of concrete landscapes, on the other hand, a high degree of similarity
      between species set of some ectoparasitic and nidicolous arthropod groups from
      different subspecies of M. gregalis. The systematic list of ectoparasitic and
      nidicolous arthropods associated with M. gregalis and representing Gamasoidea
      mites, ticks and fleas is provided.

PMID- 15493280
TI  - [Epizootological role of fleas in the Gorno-Altai natural plague focus (a
      review)].
AB  - Epizootological role of fleas in the Gorno-Altai natural plague focus (Sailugemsk
      focus) and numerous data on the flea viability are analyzed and generalized.
      Information concerning the flea natural infectivity with Yersinia pestis altaica
      is represented. Ecological peculiarities of some flea species parasitizing the
      main host, Mongolian pika Ochotona pallasi, and nature of their interrelations
      with Y. pestis are investigated. It is shown that the flea taxocenosis provides
      the permanent all year-round circulation of Y. pestis in the Gorno-Altai natural
      focus. Certain combinations of structural elements of the flea taxocenosis have a
      dominant significance in determination the circulation process at different
      phases of the annual epizootic cycle.

PMID- 15493282
TI  - [Fine structure of tarsal sensilla in the taiga tick Ixodes persulcatus
      (Ixodinae)].
AB  - The first tarsal segment of the taiga tick bears 4 general types of sensilla
      (except for sensilla forming the Haller's sensory organ on the dorsal surface of
      the tarsus): tactile mechanoreceptor sensilla of 3 types, contact chemo
      mechanoreceptor sensilla of 2 types, and double-walled pore sensilla. One of
      these types, the chemo-mechanoreceptor upper-pore sensilla, was found only in the
      Ixodinae, and not found in the examined representatives of the Amblyomminae. This
      type of sensilla was also found in the palpal receptor organ of the ixodid and
      argasid ticks.

PMID- 15493283
TI  - [Morphology and chaetotaxy of Sanguinicola armata cercaria (Trematoda:
      Sanguinicolidae)].
AB  - A morphological description of Sanguinicola armata cercaria is given. This larva
      belongs to the group of brevifurcate and apharingeal cercariae. Mouth opening is
      on ventral surface of the anterior organ. The body and branches of the furca bear
      a membrane. The body/tail ratio is much more than in other cercariae of the
      family Sanguinicolidae. The gland apparatus of the larva is represented by
      several types of secretory cells. The penetration glands form a group of 5 pairs
      of cells on the ventral side. Their ducts form a single bunch directed anterior,
      go through the anterior organ and open terminally on the proboscis, which is able
      to turn outside. Other gland cells apparently represent specialized cytones of
      the tegument. Excretory formula: 2[(1 + 1) + (1 + 1)] = 8. The external surface
      of the larva bears a small number of sensilla. Some similarities of the families
      Sanguinicolidae and Schistosomatidae in the cheatotaxy of cercaria have been
      noticed.

PMID- 15493284
TI  - [Sphinctocystis phyllodoces gen. n., sp. n. (Eugregarinida: Lecudinidae)--a new
      gregarine from Phyllodoce citrina (Polychaeta: Phyllodocidae)].
AB  - A new species of aseptate gregarine, Sphinctocystis phyllodoces gen. n., sp. n.,
      from the gut of a polychaete Phyllodoce citrina Malmgren, 1865 from White Sea is
      described. The electron and light microscopic data on trophozoits are presented.
      Taxonomy of the described species is discussed. Certain ultrastructural
      characters are included in generic and specific diagnoses. Order Eugregarinida
      Leger, 1900; suborder Aseptata Chakravarty, 1960; family Lecudinidae Kamm, 1922.
      DIAGNOSIS: Characters of the family. Free trophozoits elongated, often with
      several annular constrictions. Anterior end asymmetric, without hooks, not
      separated from the body, with small apical papilla encircled by smooth area.
      Epicyte "classical", without additional axial formations at the tops of folds;
      epicytic folds high, monomorphic in cross sections, finger-shaped, with parallel
      sidewalls. In the gut of polychaetes. DIFFERENTIAL DIAGNOSIS: The new genus
      differs from Lecudina by having asymmetric anterior end, developed smooth area
      around the apical papilla, and monomorphic epicytic folds looking finger-shaped
      in cross sections. It also differs from Lankesteria by the absence of additional
      axial formations at the tops of the epicytic folds. It differs from both named
      genera by presence of annular constrictions on the trophozoit body.
      Sphinctocystis phyllodoces sp. n. DIAGNOSIS: Characters of the genus. Free
      trophozoits elongated, large, up to 617 x x 77 um. The average height of epicytic
      folds 976 nm, thickness 194 nm; there are 6-8 apical filaments and rippled dense
      structures per fold. Nucleus spherical (ellipsoid after fixation), 24-52 microm
      along longest axis, localised in anterior third of the body, carries several
      karyosomes of various size; 25-30 nm thick fibrils (possible fragments of
      nucleolonema) may be present in karyolymph. Other stages unknown. TYPE SERIES:
      Microscope preparation with 7 trophozoits, Karacci's haematoxylin stained, is
      kept in the Zoological museum of the Moscow State University (collection number:
      Z-1). TYPE HOST: Phyllodoce citrina Malmgren, 1865 (Polychaeta: Phyllodocidae).
      LOCALISATION: Mid-gut. TYPE LOCALITY: White Sea Biological Station of the Moscow
      State University, Yeremeyevsky Rapid, Velikaya Salma Strait, Kandalaksha Bay,
      White Sea.

PMID- 15493285
TI  - [Origin and evolution of the hamuli in the monogeneans].
AB  - The hypothesis of the origin and evolution of the hamuli in monogeneans is
      proposed. It is suggested that the hamuli originated as the adult attachment
      organs of protomonogeneans inhabited the gills of the first vertebrates.
      Primarily they were represented by two lateral pairs of large hooks disposed
      anterior to the larval haptor. The fundamental direction in the evolution of
      monogeneans was the concentration of all attachment structures on the growing
      haptor. It the course of this evolutionary process, the hamuli onchoblasts
      migrated to the haptor, in which they had reached the position in the hind part
      of the haptor. The neotenic evolution of the Dactylogyridea and Gyrodactyloidea
      resulted in the forming new hamuli pairs. The hooks of opposite sides of the
      haptor are joined in a single complex within each side by the transverse plates
      (bars). So the presence of 4 hamuli is plesiomorphy for all the monogeneans and
      the presence of the transverse bars and new hamuli pairs are apomorphy for the
      Dactylogyridea and Gyrodactyloidea, whose evolution was linked with that of the
      Teleostei. The origin of the new hamuli pairs and transverse bars in the
      Dactylogyridea and Gyrodactyloidea appears to be a convergence.

PMID- 15493286
TI  - [Protective reactions of gastropod molluscs. 1. Cell reactions].
AB  - Protective reactions of molluscs are traditionally considered in cell and humoral
      aspects. The paper analyses original data and recent reference data oncell
      (phagocytic) reactions of gastropod molluscs. The main attention is paid to
      peculiarities of hemopoiesis, cell elements of hemolymph, and dynamics and
      mechanics of encapsulating the parasites.

PMID- 15493287
TI  - [The influence of infections with trematodes Bunocotyle progenetica (Hemiuridae)
      and Cryptocotyle cancavum (Heterophiidae) onto mortality of littoral molluscs
      Hydrobia ulvae (Gastropoda: Prosobranchia) in condition of extremely high
      temperature].
AB  - The effect of invasion of two trematode species, Bunocotyle progenetica
      (Hemiuridae: Bunocotylinae) and Cryptocotyle cancavum (Heterophiidae) on the host
      vitality is estimated. The mortality of infected and uninfected individuals of
      Hydrobia ulvae after different exposure time (3, 6, 9 and 12 hours) under
      extremely high temperature (+42 degrees C) was compared. The total death of the
      host was observed after 12 hours of experiment. The death rate of molluscs
      infected with B. progenetica ranged from 60 to 100% and was significantly higher
      (p < 0.01) than mortality of individuals infected with C. cancavum and uninfected
      snails in each case of exposure (3, 6 and 9 hours). At the same time the
      mortality of individuals infected with C. cancavum was significantly higher (p <
      0.05) than the mortality of uninfected snails only after 9 hours of exposure
      (13.3 and 3.1%, respectively). Difference in pathogen effects B. progenetica and
      C. cancavum is expressed in different temperature resistance of the host that may
      be explained by different localisation of redia, their motile activity and manner
      of feeding. Besides, the invasion by C. cancavum causes the sterilization and
      accelerated growth of hosts. Low decreasing of the resistance to overheating in
      snails infected with this trematode could be explained by a compensation effect
      of this infection. This compensation realizes due to the redistribution of some
      part of the reproductive energy after the sterilization. An absence of parasitic
      castration in the case of infection with B. progenetica is a key reason of such
      considerable declining of their vitality. High lethality of the host appears to
      be adaptive for the parasite with the monoxenous life cycle.

PMID- 15493288
TI  - [The trematode invasion and accumulation on heavy metals by the mollusc
      Colletopterum ponderosum (Bivalvia: Unionidae: Anodontinae)].
AB  - The influence of the trematode invasion on the accumulation of heavy metals (Cu,
      Zn, Cd, Pb) by various organs of the mollusc Colletopterum ponderosum have been
      investigated. An increase of the coefficients of accumulation and bottom
      biological accumulation, and also changes in the accumulation in pairs of heavy
      metals were noted in the infected molluscs.

PMID- 15493289
TI  - The influence of relative humidity and temperature on stability of moexipril
      hydrochloride in solid phase.
AB  - Kinetic and thermodynamic parameters of the decomposition of moexipril
      hydrochloride in solid phase in the absence and presence of humidity were
      calculated. The evaluation of stability of moexipril hydrochloride was followed
      by the HPLC method. The applied method was validated (evaluation of the following
      parameters: selectivity, linearity, precision, limit of detection (LOD), limit of
      quantification (LOQ) and repeatability). The effect of humidity on the stability
      of MHCl in solid phase at 363 K was described by the equation: In ki = ax + b =
      (0.0676 +/- 0.016) . RH% - (15.53+/-0.78). Identification of degradation products
      of MHCl were carried out by the HPLC-MS method.

PMID- 15493290
TI  - Influence of selected auxiliary substances on some physicochemical properties of
      solid dispersions containing magnesium salts.
AB  - In this survey magnesium sails in the form of solid dispersions were studied to
      examine the interaction of the drug and lecithin or Tego Betain L-7. The results
      of thermal analysis of solid dispersions containing magnesium adipate Mg[Adip]
      and compounds of this salt with glycine substituent, and the partition
      coefficient (logP) of this salts applied for solid dispersion, have been
      presented in this paper. Lecithin (45% phosphatidylcholine) or Tego Betain L-7
      (30% solution of amide betaine) have been added to magnesium salts to obtain a
      solid dispersion. The influence of auxiliary substances: Tego Betain L-7 and
      lecithin on physicochemical properties of the examined preparations has been
      assessed. The results of thermal analysis (DTA, DSC, TG) of magnesium complexes
      indicated their good thermal resistance up to the temperature of 375 K.

PMID- 15493291
TI  - Quality assessment of morphine hydrochloride solutions.
AB  - The therapeutic substances in solution prepared in pharmaceutical laboratories
      (prescribed drugs) must preserve their activity. Therefore, they must be stable
      throughout the period of storage in home conditions. The maintenance of stability
      is particularly difficult for morphine hydrochloride solutions administered
      orally to cancer patients at the last stage of the disease being at home. This
      study, aiming at the assessment of stability of morphine hydrochloride solutions,
      was performed on samples of 0.5% water solutions of the drug alone, 0.25% and
      0.5% solutions of the drug in water with chloroform as well as injection
      solutions (Morphinum hydrochloricum, 20 mg, Polfa Warsaw). All the samples were
      kept at 20 degrees C for six months. Throughout this time observations were made
      to detect changes in their appearence and pH values. Their qualitative
      composition was determined by TLC and the content of morphine was checked by UV
      spectrophotometry in an environment of 0.1 mol/l of hydrochloric acid at 285 nm.
      Results of the kinetic study permitted drawing conclusions as to the mechanism of
      the decomposition of morphine hydrochloride in the solutions studied - according
      to a simple first order reaction and determination of the rate constants (k, s(
      1)) of the process. Results of the chromatographic and spectrophotometric study
      did not show differences in the stability of water and chloroform/water solutions
      of morphine hydrochloride studied after 4 weeks and 6 months. After that time the
      decrease of morphine content was 10 and 25%, respectively.

PMID- 15493294
TI  - Antimicrobial effect of Cu(II) complexes containing oxime ligands.
AB  - The antibacterial, antifungal and antitubercular activity of Cu(II) complexes was
      studied. All the complexes have been screened against Staphylococcus aureus,
      Salmonella typhi, Candida albican, Aspergillus niger, Saccharomyces cerevisiae
      and H37Rv and found to be more toxic than the parent ligand. The activity
      increased in the order Cu(5-methyl-2,3-hexanedione dioxime)2 < Cu(5-methyl-3
      oximino-hexan-2-o-ne-hydrazone)2 < Cu(5-methyl-3-oximino-hexan-2-one
      phenylhydrazone)2.

PMID- 15493293
TI  - B16 and CLS91 mouse melanoma cells susceptibility to apoptosis after vincristin
      treatment in vitro.
AB  - Tumor cells' chemoresistance is related to the occurrence or lack of apoptosis.
      Considering the individual choice of cytostatic drugs for cancer patients and
      tumor cell resistance the research was undertaken. The viability of mouse
      melanoma B16 and ClS91 cells and apoptosis induction in vitro after treatment
      with vincristin was examined. In the future, this kind of study may play an
      important role in the efficient choice of drug dose and in limiting the side
      effects in patients treated with vincristin. Determination of vincristin's
      influence on cell proliferation kinetics, cell cycle progression based on DNA
      content and percentage of apoptosis and necrosis in B16 and ClS91 cells, was the
      object of the present study. The number of viable B16 and ClS91 cells was
      estimated by flow cytometry analysis. Apoptotic cells were detected using the
      annexin V-FITC test. Flow cytometric measurement allowed for simultaneous
      quantitation analysis of four cell subpopulations in the investigated probes. The
      subpopulations were viable, apoptotic, secondary necrotic and necrotic cells.
      After adding vincristin into B16 and ClS91 cultures, it was revealed that about
      94% ClS91 cells and 45% B16 cells died in the apoptotic way. ClS91 melanoma cells
      were more sensitive to vincristin treatment than the B16 cell line. The EC50
      value for the B16 line was 39.8 microM and for ClS91 was 16.7 microM. Cell cycle
      was established on the basis of DNA cell content after staining cells with
      propidium iodide and analysed by flow cytometry. Vincristin induced both B16 and
      ClS91 cell lines arrest in G2/M cell cycle phase. It was found a correlation
      between apoptosis occurrence in the melanoma cells and vincristin resistance.

PMID- 15493292
TI  - Indole Mannich bases and their antimycobacterial effect.
AB  - 3-[(4-arylpiperazin-1-yl)methyl]lindoles (2a-h) and 3-[(4-hydroxy-4
      phenylpiperazin-1-yl)methyl]indole (3) were prepared and characterized by 1H NMR
      and mass spectrometry. All eight compounds (2a-c, e-h and 3) tested inhibited in
      vitro the growth of Mycobacterium tuberculosis H37Rv in the range of 98-7% at a
      concentration of > or = 6.25 microg/ml. From the preliminary microbiological data
      it is possible to observe that a simple increasing of lipophilicity of the
      compounds tested to above logPcalc> or =3.8 significantly increases the potencies
      of their antitubercular action.

PMID- 15493295
TI  - Chiral mixed ligand Co(II) and Ni(II) complexes: synthesis and biological
      activity.
AB  - Chiral mixed ligand (CML) transition metal complexes of the type MQL.2H2O, where
      M is Co(II)/Ni(II), Q is deprotonated 8-hydroxyquinoline and L is a deprotonated
      chiral saccharide such as (+)-glucose and (-)-fructose, have been synthesized.
      The metal complexes have been characterized on the basis of elemental analysis
      and various physicochemical techniques such as molar conductance, specific
      rotation measurements, magnetic, spectral and thermal studies. The cup-plate
      method has been used to study the antibacterial activity of the compounds against
      some of the pathogenic bacteria such as C. diphtheriae, E. coli, S. typhi, S.
      dysenteriae, S. aureus and V. cholerae. The antifungal activity of the complexes
      against some of the pathogenic fungi such as Candida albicans and Aspergillus
      niger has been studied by the tube dilution method. The results have been
      compared against those of controls, which were screened simultaneously. The
      complexes have been screened for acute oral toxicity in albino rats. The method
      of Litchfield and Wilcoxon has been used to determine the LD50 values.

PMID- 15493296
TI  - Synthesis, characterization and antimicrobial activity of 1,5-bis[2-(hydroximino)
      1-methyl-3-oxo-butane-1,1-diyl]thiocarbonohydrazide and 1,5-bis[2-(hydroximino) 
      3-oxo-1-phenyl-butane-1,1-diyl]thiocarbonohydrazide.
AB  - 1,5-Bis[2-(hydroximino)-1-methyl-3-oxo-butane-1,1-diyl]thiocarbonohydrazide [IV]
      and 1,5-bis[2-(hydroximino)-3-oxo-1-phenyl-butane-1,1-diyl]thiocarbonohydrazide
      [V] were synthesized by the reaction of thiocarbonohydrazide [I] with either 3
      (hydroximino)-pentane-2,4-dione [II] or 2-(hydroximino)-1-phenyl-butane-1,3-dione
      [III] in a 1:2 molar proportion, respectively. Compounds [IV] and [V] were
      characterized by elemental analyses, IR and PMR spectroscopic studies. These
      newly synthesized compounds have been screened or their antimicrobial activity
      against S. aureus, S. typhi. C. albicans, T. mentagrophytes, T. rubrum and M.
      tuberculosis.

PMID- 15493297
TI  - Synthesis of new hexahydro- and octahydropyrido[1,2-c]pyrimidine derivatives with
      an arylpiperazine moiety as ligands for 5-HT1A and 5-HT2A receptors. Part III.
AB  - The preparation of new 4-aryl-hexahydropyridol 1,2-c]pyrimidine derivatives III
      XXVI with an arylpiperazinylbutyl moiety in N-2 position has been described.
      Multi-stage synthesis techniques were used to obtain 4-arylhexahydro-1H,3H
      pyrido[1,2-c]pyrimidine-1,3-dione Ia-f derivatives, being the starting compounds
      for further modification. N-alkylation of the imide group in compounds Ia-f
      followed, using 1,4-dibromobutane to yield bromobutyl derivatives IIa-f. The
      final products III-XXVI were obtained by condensation of aryl- or heteroaryl-
      piperazine with the bromobutyl derivatives IIa-f. Compounds XII, XIV, XIX, XX,
      XXIV-XXVI will be submitted to a pharmacological investigation for their affinity
      towards 5-HT1A, 5-HT2A and alpha1 adrenergic receptor, using radioligand binding
      assay.

PMID- 15493298
TI  - Interaction of mianserin and some hypotensive drugs in Wistar rats.
AB  - Mianserin is thought to exert little effect on the cardiovascular system. In fact
      its safety in comparison with tricyclic drugs is high. Various experiments gave
      varying results as for the influence of the drug on arterial blood pressure in
      people and animals. Therefore, a study was undertaken in Wistar rats to evaluate
      interactions of mianserin administered intraperitoneally as a single dose, and
      for 21 days with 3 hypotensive drugs showing different mechanism of action
      (propranolol, enalapril, prazosine). The systolic, diastolic and mean blood
      pressure was measured with a LETICA apparatus. The results of the study revealed
      that administration of mianserin in normotensive rats leads to a short-term
      decrease in blood pressure and significantly enhanced the hypotensive effect of
      prazosine. Repeated doses of mianserin lead to a temporary increase in blood
      pressure after 2 weeks of administration. Single and repeated administration of
      mianserin did not change the hypotensive effect of propranolol and enalapril.
      Three-week therapy with mianserin significantly enhanced the hypotensive effect
      of prazosine.

PMID- 15493299
TI  - Influence of sertraline on the antinociceptive effect of morphine, metamizol and
      indomethacin in mice.
AB  - Interaction between analgesic and various psychotropic drugs constitute a subject
      of many research investigations. Literature data considering this issue are often
      inconsistent. Sertraline is one of the most potent drugs in the family of
      selective serotonine reuptake inhibitors (SSRIs). The influence of sertraline (5
      mg/kg) on antinociceptive effect of morphine (10 mg/kg), metamizol (500 mg/kg)
      and indomethacin (10 mg/kg or 1.4 mg/kg) was investigated in a mouse model using
      the tail-flick and hot-plate tests. All drugs were injected intraperitoneally.
      Sertraline was administered to mice 30 min before applying the analgesic drugs.
      Measurement of nociception was performed within 2 h after sertraline
      administration. The research studies were futher conducted with multiple (14
      days) drug dosage. Sertraline after single dose increased the antinociceptive
      effect of morphine (in the hot-plate test) and metamizol and indomethacin (only
      in the tail-flick test). Sertraline after 14 day administration decreased
      analgesic effect of morphine (only in the hot-plate test). Sertraline applied for
      14 days increased the antinociceptive effect of indomethacin. Sertraline alone
      after multiple doses increased pain reaction time. The results of experiments
      suggest the role of sertraline in nociception and possibility of interaction
      between sertraline and analgesic drugs.

PMID- 15493301
TI  - No money? No problem.

PMID- 15493302
TI  - Having faith in each other: not-for-profit giant Ascension Health hooks up with
      United Surgical Partners for ASC joint venture.
AB  - In the biggest deal of its kind, not-for-profit giant Ascension is going to build
      ambulatory surgery centers with for-profit United Surgical Partners, which
      already has a deal with Baylor, left. "Hospitals are realizing that outpatient
      services are the future. This strategy is sound," one healthcare consultant said.

PMID- 15493300
TI  - Antidepressant--like properties of ACEA (arachidonyl-2-chloroethylamide), the
      selective agonist of CB1 receptors.
AB  - The antidepressant effect of ACEA (arachidonyl-2-chloroethylamide), a selective
      agonist of CB1 receptors, and its interaction with fluoxetine were studied in
      mice. ACEA (1.0 and 2.0 mg/kg i.p.) reduced the immobility time in the forced
      swimming test and attenuated the head - twitch response to L-5-HTP. The
      concomitant administration of ACEA (1.0 mg/kg i.p.) and fluoxetine (20 mg/kg
      i.p.) resulted in the strongest shortening of immobility time, significant in
      comparison with both ACEA and fluoxetine given alone. The obtained results
      indicate that ACEA may have antidepressant efficacy and shows a synergistic
      effect when given with fluoxetine in the forced swimming test.

PMID- 15493303
TI  - Special effects: early finding say niche facilities have little impact.

PMID- 15493305
TI  - Who's to blame? Republicans, Democrats square off on coverage costs.

PMID- 15493304
TI  - Cost of coverage: premiums rise by an average of 11.2%: Kaiser study.

PMID- 15493306
TI  - Surveying the costs: providers left to assess if JCAHO increases are worth it.

PMID- 15493307
TI  - Dodging a bullet: Scruggs has four hospital class-action suits dismissed.

PMID- 15493308
TI  - CMS vs. Congress: HHS refuses to act on GAO opinion regarding Scully.

PMID- 15493309
TI  - Expensive debate: Tenet disputes report calling its hospitals most costly.

PMID- 15493310
TI  - Care checkup: project seeks to improve bedside manner.

PMID- 15493311
TI  - Becoming an interpretive center. HIMSS unit's mission: make sense of health IT
      data.

PMID- 15493312
TI  - Where bad news goes: administration can hide medicare premium hikes but can't run
      from truth.

PMID- 15493313
TI  - Inaction is not an option: but plans abound for policymakers to choose from in
      solving coverage crisis.

PMID- 15493314
TI  - Behavioral modification: researchers continue to study the reverberations of a
      for-profit's entry into a hospital market. The findings are definitively mixed.

PMID- 15493315
TI  - Food fight. When it comes to catering to patients, outsourcing firms still hold a
      small slice of the hospital food-service business vs. in-house operations. But
      who serves up the best quality and efficiency?

PMID- 15493316
TI  - The misconception of the regression-based discrepancy operationalization in the
      definition and research of learning disabilities.
AB  - In this article, I argue that the regression-based discrepancy method used in the
      diagnosis of learning disabilities is invalid because it is inconsistent with the
      underlying underachievement concept of which it is intended to be the
      operationalization. I mathematically demonstrate that the regression-based
      discrepancy method largely reflects achievement-specific determinants, thereby
      defeating its own object of describing aptitude-achievement discrepancies. The
      implications for research examining the role of intelligence in learning
      disabilities are outlined.

PMID- 15493318
TI  - Will the real discrepant learning disability please stand up?
AB  - Willson and Reynolds (in this issue) challenged my thesis that the regression
      based discrepancy method (RDM) is not a valid tool to detect aptitude-achievement
      discrepancies. In this response, I show that the statistical and theoretical
      counterarguments of Willson and Reynolds are based on a misreading of the
      statistical models presented. Furthermore, I demonstrate that the regression
      adjustment, which is largest for lower correlations, is the direct source of the
      lack of validity of the RDM procedure. Nevertheless, RDM can be considered a
      valid method to measure an achievement component that is unrelated to
      intelligence.

PMID- 15493317
TI  - Misconceptions in Van den Broeck's representation of misconceptions about
      learning disability research.
AB  - The methods and conclusions of Van den Broeck (in this issue) are evaluated from
      two perspectives: (a) statistical considerations and (b) theoretical models of IQ
      and achievement, specifically reading achievement. We consider the statistical
      model proposed by Van den Broeck for the regression-based discrepancy model (RDM)
      to be either irrelevant or conceptually inconsistent with current models of IQ
      and achievement. The resulting simulation produced exemplar cases that are not
      realistic in terms of practice. The theoretical representations of IQ and
      achievement were, in our understanding, inconsistent with contemporary models of
      either. We suggest that acceptable models support the use of the RDM as it has
      been proposed by us and by others as one component of the determination of the
      presence or absence of a learning disability.

PMID- 15493319
TI  - The incidence and nature of letter orientation errors in reading disability.
AB  - Letter orientation confusions (reversals) in the reading and writing of 10-year
      old children with and without reading disability were investigated to determine
      whether reading disability is associated with letter orientation errors and to
      identify the nature of the errors. In a variety of tasks measuring letter
      orientation confusions in reception (reversal detection and recognition) and
      production (controlled writing, copying), individuals with reading disability
      made more orientation confusions than average readers. Orientation errors were
      more frequent for reversible than for nonreversible items in tasks involving long
      term memory processes. The results did not appear to be related to group
      differences in attention or speed of motor responding. Possible sources of
      orientation confusions, including deficient magnocellular system processing,
      mislabeling, and overreliance on visual strategies, are discussed.

PMID- 15493320
TI  - A comparison of multiple methods for the identification of children with reading
      disabilities.
AB  - There has been considerable discussion of the methods used for the identification
      of children with reading disabilities. This study examined three different
      methods that could be used in the identification of children with reading
      disabilities and their consistency with teacher ratings of behaviors believed to
      be associated with reading disabilities. Standardized, norm-referenced measures
      of achievement, phonological processing measures, and curriculum-based measures
      of reading fluency were used with 40 children in Grades 1 and 2. Comparisons were
      made to determine which measures, if any, differentiated between children
      referred for reading disabilities (n = 20) and children who were progressing
      typically in reading in their general education classroom settings (n = 20). The
      results indicated significant between-group differences on standardized, norm
      referenced measures of reading recognition, word attack, and comprehension;
      phonological measures of blending nonwords and elision; and reading fluency.
      Teacher ratings on the Dyslexia Screening Instrument were consistent with teacher
      beliefs regarding children's progress in reading. All measures were found to
      correlate significantly with each other. However, correlations were generally in
      the moderate range, suggesting that the measures used did not measure the same
      reading skills or, in the case of phonological processing, the underlying
      abilities believed to be necessary for reading. Given the differences in tasks
      and the moderate correlations, it is likely that the choice of measures may
      affect the conclusions reached regarding a student's reading ability.

PMID- 15493321
TI  - Relationship of rapid automatized naming and phonological awareness in early
      reading development: implications for the double-deficit hypothesis.
AB  - It is widely accepted that deficits in phonological awareness skills are related
      to reading difficulties. Recently, another source of reading difficulty has been
      identified that involves naming speed, and combined impairments in phonological
      skills and naming speed will produce more severe reading deficits than single
      deficits in either of these cognitive skills. The purpose of this study was to
      investigate the consequences of grouping children based on the presence or
      absence of deficits in these skills. We demonstrate that the greater severity of
      reading impairment found in children with a double deficit could be due in part
      to a statistical artifact caused by grouping children based on their performance
      on two correlated continuous variables. This artifact also makes it difficult to
      establish the relative impact of deficits in naming speed on reading ability
      independent of deficits in phonological awareness.

PMID- 15493322
TI  - Lexical access in college students with learning disabilities: an
      electrophysiological and performance-based investigation.
AB  - The purpose of this study was to compare the semantic processing abilities of
      college students with learning disabilities (LD) to those of their peers without
      learning disabilities (NLD) who were matched for age, gender, and intelligence.
      Participants were compared on results from the Test of Adolescent/Adult Word
      Finding (TAWF) and from event-related potential (N400) sampling to the processing
      of semantically incongruous sentences. The LD and NLD groups did not
      significantly differ in accuracy on the TAWF; however, students with LD
      demonstrated a significantly greater number of delayed responses. The LD group's
      N400 responses were significantly delayed at the Pz electrode site. Effect size
      indicators also revealed somewhat reduced amplitudes at Fz and Cz locations. The
      significant delays of the students with LD on standardized testing and on N400
      suggest an inefficiency in the semantic processing of these individuals, in both
      automatic and attention-based aspects of lexical access.

PMID- 15493323
TI  - Sleep disturbances in adolescents with symptoms of attention
      deficit/hyperactivity disorder.
AB  - We evaluated 32 nonmedicated male adolescents diagnosed with attention
      deficit/hyperactivity disorder (ADHD) in childhood, 35 male adolescents similarly
      diagnosed who were receiving methylphenidate (MPH), and 77 control boys. Both
      ADHD groups completed self-report questionnaires assessing sleep disturbances;
      weekday and holiday sleep duration; and symptoms of ADHD, anxiety, and
      depression. Parents and teachers rated the severity of the participants' ADHD.
      The control group completed self-report questionnaires assessing sleep
      disturbances. We found that nonmedicated participants and controls did not differ
      in the severity of sleep disturbance. In contrast, the medicated participants
      demonstrated a significantly greater severity of sleep disturbance compared with
      the nonmedicated participants and reported elevated levels of symptoms of ADHD,
      anxiety, and depression. Specific analyses showed that depressive symptoms
      contributed significantly to the degree of sleep disturbance when controlling for
      ADHD diagnosis and MPH treatment. These findings suggest that among adolescents
      with ADHD symptoms, the severity of symptoms of depression may contribute to the
      degree of sleep disturbance in addition to the effect of their primary disorder
      and MPH treatment.

PMID- 15493324
TI  - EEG analysis of children with attention-deficit/hyperactivity disorder and
      comorbid reading disabilities.
AB  - This study investigated electroencephalographic differences between two groups of
      children with attention-deficit/hyperactivity disorder, combined type, with
      reading disabilities (ADHD + RD) or without (ADHD) and typical control
      participants. Twenty participants were included in each group. All participants
      were between the ages of 8 and 12 years, and groups were matched on age and
      gender. The electroencephalographic (EEG) was recorded during an eyes-closed
      resting condition from 21 monopolar derivations, which were clustered into nine
      regions for analysis. The EEGs were Fourier-transformed to provide absolute and
      relative power estimates for the delta, theta, alpha, and beta bands. Ratio
      coefficients were also calculated for the theta/alpha and theta/beta ratios.
      Compared with controls, the clinical groups demonstrated the increased slow-wave
      and reduced fast-wave activity commonly reported in the ADHD literature. The ADHD
      + RD group had more relative theta, less relative alpha, and a higher theta/alpha
      ratio than the ADHD group. A number of hemispheric differences were also found in
      the delta and alpha bands. These results suggested that some of the EEG
      divergences found in the ADHD + RD group represent an electrophysiological
      component associated with the reading disability that is independent of the EEG
      divergences found in ADHD.

PMID- 15493325
TI  - Illegitimate recombination mediated by double-strand break and end-joining in
      Escherichia coli.
AB  - The frequency of illegitimate recombination has been measured by a lambda bio
      transducing phage assay during the induction of the E. coli lambda cI857 lysogen.
      Illegitimate recombination falls into two classes, short homology-independent and
      short homology-dependent illegitimate recombination. The former involves
      sequences with virtually no homology, and is mediated by DNA topoisomerases and
      controlled by the DNA binding protein HU. The latter is induced by UV irradiation
      or other DNA damaging agents and requires short regions of homology, usually
      contain 4 to 13 base pairs, at sites involved in recombination. It has been shown
      that the RecJ exonuclease promotes short homology-dependent illegitimate
      recombination, but that the RecQ helicase suppresses it. In addition, we have
      shown that the overexpression of RecE and RecT enhances the frequencies of
      spontaneous and UV-induced illegitimate recombination and that the RecJ, RecF,
      RecO, and RecR functions are required for this RecE-mediated illegitimate
      recombination. Moreover, we have also indicated that RecQ plays a role in the
      suppression of RecE-mediated illegitimate recombination, with the participation
      of DnaB, Fis, ExoI, and H-NS. Models have been proposed for these modes of
      recombination: the DNA gyrase subunit exchange model for short homology
      independent illegitimate recombination and the "double-strand break and join"
      model for short homology-dependent illegitimate recombination. Many features of
      these models remain to be tested in future studies.

PMID- 15493326
TI  - Genetic and physiological regulation of non-homologous end-joining in mammalian
      cells.
AB  - Repair of DSBs is important to prevent chromosomal fragmentation, translocations
      and deletions. To investigate the process in NHEJ, we have established an in
      vitro system to clarify the measurement and analysis of the efficiency and the
      fidelity of rejoining of DSBs, and applied the method to investigate NHEJ in
      human cells derived from patients suffering from cancer-prone hereditary
      diseases. A DSB was introduced in plasmid pZErO-2 at a specific site within the
      ccdB gene that is lethal to E. coli cells, and treated with nuclear extracts from
      human cells. The efficiency of rejoining in the nuclear extract from an A-T cell
      line was comparable to that from a control cell line. However, the accuracy of
      rejoining was much lower for the A-T cell extract than for the control cell
      extract. All mutations were deletions, most of which contained short direct
      repeats at the breakpoint junctions. The deletion spectrum caused by the A-T
      nuclear extract was distinct from that by the control extract. These results
      indicate that A-T cells have certain deficiencies in end-joining of double-strand
      breaks in DNA. The extract from BS cells also showed the similar activity and the
      lower fidelity of rejoing compared to that from normal cells. From the sequencing
      analysis of the junction of DSBs, it is speculated that the defect in the BLM
      helicase might cause irregular rejoining of DSBs. Radioadaptive response is the
      acquirement of cellular resistance to ionizing radiation by prior exposure to low
      dose. We investigated the in vitro end-joining activity of DNA ends in
      radioadaptive cells. Both the efficiency and the fidelity of rejoining in the
      cells pre-exposed to low dose are increased comparing to those without pre
      exposure. We also investigated the joining activity of DNA ends in p53-deficient
      cells. Pre-irradiation caused no apparent alteration in both the efficiency and
      fidelity of end-joining. These results suggest that the exposure to low dose
      activates a cellular function to repair DSBs efficiently, which is dependent on
      p53. These results indicate that NHEJ pathway is regulated by many factors;
      genetic regulation by ATM and BLM, and physiological conditions such as
      irradiation with ionizing radiation. The observations also suggest that in some
      occasions p53 might play a key role in NHEJ.

PMID- 15493327
TI  - The function of RecQ helicase gene family (especially BLM) in DNA recombination
      and joining.
AB  - Bloom syndrome is a rare autosomal recessive genetic disorder characterized by
      lupus-like erythematous telangiectasias of the face, sun sensitivity, stunted
      growth, and immunodeficiency. Chromosome instability syndromes have a common
      feature, being associated at high frequency with neoplasia. BS is considered as
      one of the chromosome instability syndromes since the fibroblasts or lymphocytes
      of BS patients show excessive spontaneous chromosome instability. The causative
      gene of BS (BLM) was identified as a RecQ helicase homologue. In this review, we
      showed the characteristic phenotypes of BS, especially two Japanese siblings. In
      the latter of the review, the functional domains of BLM, those are nuclear
      localization signal and the interacting proteins such as ATM, are shown. Several
      lines of reports indicates that BLM helicase is involved in the re-initiation of
      DNA replication at sites where replication forks have arrested or collapsed. To
      elucidate the precise function of RecQ helicase in DNA repair and replication
      aims not only to improve our understanding of the molecular basis for
      tumorigenesis, but also to extend the range of potential therapeutic targets.

PMID- 15493328
TI  - Nijmegen breakage syndrome and DNA double strand break repair by NBS1 complex.
AB  - The isolation of the NBS1 gene revealed the molecular mechanisms of DSB repair.
      In response to DNA damage, histone H2AX in the vicinity of DSBs is phosphorylated
      by ATM. NBS1 then targets the MRE11/RAD50 complex to the sites of DSBs through
      interaction of the FHA/BRCT domain with gamma-H2AX. NBS1 complex binds to damaged
      DNA directly, and HR repair is initiated. To collaborate DSB repair, ATM also
      regulates cell cycle checkpoints at G1, G2, and intra-S phases via
      phosphorylation of SMC, CHK2 and FANCD2. The phosphorylation of these proteins
      require NBS1 complex. Thus, NBS1 has at least two important roles in genome
      maintenance, as a DNA repair protein in HR pathway and as a signal modifier in
      intra-S phase checkpoints. NBS1 is also known to be involved in maintenance of
      telomeres, which have DSB-like structures and defects here can cause telomeric
      fusion. Therefore, NBS1 should be a multifunctional protein for the maintenance
      of genomic integrity. Further studies on NBS1 will provide insights into the
      mechanisms of DNA damage response and the network of these factors involved in
      genomic stability.

PMID- 15493329
TI  - Cell death promoted by homologous DNA interaction from bacteria to humans.
AB  - Pairing between homologous DNA controls cellular functions including double
      strand break repair, mitotic recombination, and progression of DNA replication
      forks, as well as chiasma formation during meiosis. Here I summarize that
      homologous interaction could promote the cell killing in bacteria, yeast, and
      multicellular organisms. The mechanisms of cell killing are categorized into two
      types: (1) the killing due to the accumulation of extrachromosomal DNA; (2) the
      killing induced by Holliday junction structures. I propose that the mechanisms of
      such killing function as novel apoptotic pathways in the cells carrying severe
      DNA damages to eliminate such damages from cell population.

PMID- 15493330
TI  - Gpt delta transgenic mouse: a novel approach for molecular dissection of deletion
      mutations in vivo.
AB  - Human genome is continuously exposed to various DNA damaging agents including
      reactive oxygen species. Of various forms of DNA damage, double-strand breaks
      (DSBs) in DNA are the most detrimental because of the mutagenicity and
      cytotoxicity. To combat the serious threats posed by DSBs, cells evolved various
      homologous and non-homologous recombination repair mechanisms. However, some
      repair mechanisms appear to be involved in the induction of genome rearrangements
      such as deletions. To analyze the deletion mutations in a whole body system, gpt
      delta mice were established. In this mouse model, deletions in lambda DNA
      integrated in the chromosome are preferentially selected as Spi- phages, which
      can then be subjected for molecular analysis. Here, we reported the sequence
      characteristics of deletions induced by ionizing radiations in the liver,
      ultraviolet light B in the epidermis, mitomycin C in the bone marrow and
      heterocyclic amine PhIP in the colon. To our knowledge, this is the first report
      in which in vivo deletion mutations are systematically analyzed at the molecular
      level. About half of the large deletions occur between short direct-repeat
      sequences and the remainder had flush ends, suggesting that they are generated
      during the repair of DSBs in DNA. The results also suggest that mutation
      induction and repair mechanisms may vary depending on the type of organs/tissues
      examined, i.e., germ cells versus somatic cells or highly proliferating cells
      versus slowly proliferating cells. Possible mechanisms of intrachromosomal
      deletion mutations are discussed.

PMID- 15493331
TI  - Intermediate molecules generated by transposase in the pathways of transposition
      of bacterial insertion element IS3.

PMID- 15493332
TI  - Genetics and epigenetics in flower pigmentation associated with transposable
      elements in morning glories.
AB  - Among the genus Ipomoea, three morning glories, I. nil (the Japanese morning
      glory), I. purpurea (the common morning glory), and I. tricolor, were
      domesticated well for floricultural plants, and many spontaneous mutants
      displaying various flower pigmentation patterns were isolated. Most of these
      spontaneous mutations were found to be caused by the insertion of DNA
      transposable elements in the genes for the anthocyanin pigmentation in flowers,
      and many of them exhibited variegated flowers, such as white flowers with
      pigmented spots and sectors. Here, we describe the historical background of the
      mutants displaying variegated flowers and review the genetic and epigenetic
      regulation in flower pigmentation associated with transposable elements of these
      morning glories. The flecked, speckled, r-1, and purple mutations in I. nil were
      caused by insertions of Tpn1 and its relatives in the En/Spm superfamily, Tpn2,
      Tpn3, and Tpn4, into the genes for anthocyanin coloration in flowers, i.e., DFR
      B, CHI, CHS-D, and InNHX1, respectively. Similarly, the flaked and pink mutants
      of I. purpurea have distantly related elements, Tip100 and Tip201, in the Ac/Ds
      superfamily inserted into the CHS-D and F3'H genes, respectively. The flower
      variegation patterns can be determined by the frequency and timing of the
      excision of these transposons, and their stable insertions produce plain color
      flowers without generating pigmented spots or sectors; furthermore, both genetic
      and epigenetic regulation appeared to play important roles in determining the
      frequency and timing of the excision of the transposons. However, flower
      variegation is not always associated with the excision of an integrated DNA
      transposon from one of the genes for anthocyanin pigmentation. The mutant Flying
      Saucers of I. tricolor displaying variegated flowers was found to have the
      transposon ItMULE1 inserted into the DFR-B promoter region, but no excision of
      ItMULE1 from the DFR-B could be detected in the variegated flower lines. The
      instable pearly-vrg allele in cv. Flying Saucers is likely to be an epiallele
      because the DNA methylation in the DFR-B promoter appeared to be associated with
      flower pigmentation.

PMID- 15493333
TI  - Transposition mechanisms and biotechnology applications of the medaka fish Tol2
      transposable element.
AB  - The Tol2 element of the medaka fish is a member of the hAT (hobo/Activator/ Tam3)
      transposable element family. About 20 copies are present in the medaka fish
      genome and, unlike many other hAT family elements, virtually all the copies are
      autonomous or potentially autonomous, containing an intact transposase gene.
      Excision of Tol2 is not precise at the nucleotide sequence level, excision foot
      prints being heterogeneous. In more than half of excision events, however,
      breakage and rejoining of DNA molecules occur within the 8-bp target site
      duplication region, removing the entire Tol2 sequence and retaining parts of the
      target site duplications. In the reminder of the excision events, either the left
      or the right terminal region is left and the other end is lost together with its
      flanking region. Thus, there might be two different mechanisms of excision.
      Insertion of Tol2 occurs without detectable preference for target sequences and
      creates a target site duplication of exactly 8 bp. In addition to the medaka fish
      and related fish species, Tol2 transposes in mammalian cells in culture,
      including human and mouse examples. Autonomy is also retained in these cases. A
      gene transfer vector using Tol2 has already been established in fish. Foreign DNA
      fragements inserted in Tol2 can be efficiently delivered to the chromosomes by
      transposition. The latest version of the vector contains, between the Tol2
      terminal regions, a bacterial drug-resistance gene and a plasmid replication
      origin. This allows simple recovery of insertion regions, as plasmid DNA, from
      genomic DNA of transformants. Modification of this system for other vertebrates,
      especially for mammals, are now in progress.

PMID- 15493335
TI  - Molecular mechanism of VDE-initiated intein homing in yeast nuclear genome.
AB  - In Saccharomyces cerevisiae, VMA1 intein encodes a homing endonuclease termed VDE
      which is produced by an autocatalytic protein splicing reaction. VDE introduces a
      DSB at its recognition sequence on intein-minus allele, resulting in the lateral
      transfer of VMA1 intein. In this review, we summarize a decade of in vitro study
      on VDE and describe our recent study on the in vivo behavior of both VDE and host
      proteins involved in intein mobility. Meiotic DSBs caused by VDE are repaired in
      the similar pathway to that working in meiotic recombination induced by Spo11p
      mediated DSBs. Meiosis-specific DNA cleavage and homing is shown to be guaranteed
      by the two distinct mechanisms, the subcellular localization of VDE and a
      requirement of premeiotic DNA replication. Based on these lines of evidence, we
      present the whole picture of molecular mechanism of VDE-initiated homing in yeast
      cells.

PMID- 15493334
TI  - Structure and function of the shufflon in plasmid R64.
AB  - Conservative site-specific recombination plays key roles in creating biological
      diversity in prokaryotes. Most site-specific inversion systems consist of two
      recombination sites and a recombinase gene. In contrast, the shufflon multiple
      inversion system of plasmid R64 consists of seven sfx recombination sites, which
      separate four invertible DNA segments, and the rci gene encoding a site-specific
      recombinase of the integrase family. The rci product mediates recombination
      between any two inverted sfx sites, resulting in the inversion of four DNA
      segments independently or in groups. Random shufflon inversions construct seven
      pilV genes encoding constant N-terminal segment with different C-terminal
      segments. The pilV products are tip-located adhesins of the type IV pilus, called
      the thin pilus, of R64 and recognize lipopolysaccharides of recipient bacterial
      cells during R64 liquid matings. Thus, the shufflon determines the recipient
      specificity of liquid matings. Rci protein of R64 was overexpressed, purified,
      and used for in vitro recombination reactions. The cleavage and rejoining of DNA
      strands in shufflon recombinations were found to take place in the form of a 5'
      protruding 7-bp staggered cut within sfx sequences. Thus, the sfx sequence is
      asymmetric: only the 7-bp spacer sequence and the right arm sequence are
      conserved among various R64 sfxs, whereas the sfx left arm sequences are not
      conserved. Rci protein was shown to bind to entire sfx sequences, suggesting that
      it binds to the right arms of the sfx sequences in a sequence-specific manner and
      to their left arms in a non-sequence-specific manner. The sfx left arm sequences
      greatly affected the shufflon inversion frequency. The artificial symmetric sfx
      sequence, in which the sfx left arm was changed to the inverted repeat sequence
      of the right arm, exhibited the highest inversion frequency. Rci-dependent
      deletion of a DNA segment flanked by two symmetric sfx sequences in direct
      orientation was observed, suggesting that the asymmetry of sfx sequences may
      prevent recombination between sfx sequences in direct orientation in the R64
      shufflon. The Rci C-terminal domain was not required for recombination using the
      symmetric sfx sequence. A model, where the C-terminal domain of Rci protein plays
      a key role in the sequence-specific and non-specific binding of Rci to asymmetric
      sfx sites, was proposed. Site-specific recombination in the temperate phage Mx8
      of M. xanthus was also described. The Mx8 attP site is located within the coding
      sequence of the Mx8 intP gene. Therefore, the integration of Mx8 into the M.
      xanthus chromosome results in the conversion of the intP gene into a new gene,
      intR. As a result of this conversion, the 112-amino-acid C-terminal sequence of
      the intP product is replaced with a 13-amino acid sequence of the intR product.
      The C-terminal domain of Mx8 IntP recombinase is only required for integration
      and not for excision.

PMID- 15493336
TI  - [The effect of mometasone furoate on mucociliary clearance in patients with
      perennial allergic rhinitis].
AB  - OBJECTIVES: We investigated the effect of mometasone furoate on mucociliary
      clearance in patients with perennial allergic rhinitis. PATIENTS AND METHODS: The
      study included 25 patients (16 females, 9 males; mean age 30 years; range 18 to
      50 years) with perennial allergic rhinitis. Mometasone furoate (nasal spray) was
      administered at a dose of 2 puffs (100 microgr) to each nostril daily for a
      month. Mucociliary clearance was evaluated by the saccharin test before and after
      treatment. RESULTS: The mean mucociliary clearance time was 6.89 +/- 0.64 minutes
      before the treatment and 7.18 +/- 0.54 minutes after the treatment. No
      significant delay in the mucociliary clearance was detected (p > 0.05). The mean
      mucociliary clearance time did not differ significantly between male and female
      patients (p > 0.05). CONCLUSION: The results suggest that mometasone furoate do
      not affect mucociliary clearance in patients with perennial allergic rhinitis.

PMID- 15493337
TI  - [The beneficial effect of selenium against induction of squamous cell carcinoma
      of the tongue in rabbits].
AB  - OBJECTIVES: In a rabbit model of squamous cell carcinoma of the tongue, we
      monitored histopathologic changes and assessed the effect of selenium against
      carcinogenesis. STUDY DESIGN: The study included 36 male albino New Zealand
      rabbits. To induce squamous cell carcinoma of the tongue, 9,10-dimethyl-1,2
      benzanthracene (DMBA)-acetone solution was applied three times a week for a
      duration of 20 weeks under anesthesia with xylazine hydrochloride and ketamine.
      The rabbits were randomly assigned to receive either pure tap water (24 rabbits)
      or tap water supplemented with 4 ppm sodium selenite (12 rabbits). One rabbit in
      each group was sacrificed at the end of 4, 8, 12 and 16 weeks, and the remaining
      rabbits at the end of 20 weeks for macroscopic and microscopic examination of the
      tongue. RESULTS: By week 20, two rabbits in the selenium group, and nine rabbits
      receiving tap water died from acute necrotizing bronchopneumonia due to
      pasteurellosis. Dysplasia was significantly less in selenium-receiving rabbits
      (16.7% vs 66.7%, p < 0.0001), and its development manifested a delayed onset.
      Carcinoma in situ was detected in 25% of tap water-receiving rabbits that
      remained alive by week 19 to 20, while none of the rabbits had carcinoma in situ
      in the selenium group. CONCLUSION: Our data demonstrate that selenium has an
      inhibitory and preventive effect against chemically-induced rabbit tongue
      carcinogenesis.

PMID- 15493338
TI  - [Total pharyngolaryngoesophagectomy and gastric pull-up: an evaluation of 10
      cases].
AB  - OBJECTIVES: We evaluated the patients who underwent total
      pharyngolaryngoesophagectomy (T-PLE) and gastric pull-up (GPU) for hypopharyngeal
      tumors extending to the cervical esophagus. PATIENTS AND METHODS: Ten patients (8
      females, 2 males; mean age 50 years; range 39 to 60 years) were treated with T
      PLE and GPU, total thyroidectomy, and bilateral neck dissection including zone
      VI. Histopathologic diagnoses were squamous cell carcinoma (n = 8), basaloid
      squamous cell carcinoma (n = 1), and adenoid cystic carcinoma (n = 1). Clinical
      stage, tumor stage, and nodal status were as follows: eight patients IVA, two
      patients III; eight patients T4a, two patients T3; seven patients N+ (6 N2, 1
      N1), three patients N0. RESULTS: Three patients (30%) died within a month after
      surgery. Two patients were alive after the seventh and first postoperative years,
      respectively. The remaining five patients died because of causes related (n = 3)
      to or unrelated (n = 2) to carcinoma. Survival was 20% for one year, and 14.3%
      for five years. Histopathologically, surgical margins were free of tumor in nine
      cases. The mean time to the initiation of oral feeding was nine days (range 4 to
      14 days), and the mean hospital stay was 23 days (range 12 to 36 days).
      CONCLUSION: Early initiation of oral feeding and relatively short hospitalization
      periods make T-PLE and GPU an appropriate palliative procedure, increasing the
      quality of life for many patients.

PMID- 15493339
TI  - A case of nasal leiomyosarcoma: the first comparative genomic hybridization
      analysis.
AB  - Leiomyosarcomas are rare in the head and neck region. The treatment of choice is
      surgical resection. We present a case of leiomyosarcoma in a 50-year-old female
      patient, arising from the inferior turbinate. The tumor was resected by a
      transnasal microendoscopic approach and no evidence for tumor recurrence was
      found during an endoscopic and radiologic follow-up of two years. Cytogenetic
      analysis by means of comparative genomic hybridization revealed chromosomal gains
      at 4p13p15, 6p21p22, 7q22qter, 9q22qter and chromosomal losses at 10q22qter and
      19p12p13.1. With augmented experience, the transnasal approach may be appropriate
      to resect circumscribed malignant tumors located in the nasal cavity.

PMID- 15493340
TI  - Cavernous lymphangioma in the laryngeal ventricle in an adult patient.
AB  - Lymphangiomas of the larynx are quite rare and even rarer in adults. Isolated
      cavernous lymphangioma in the laryngeal ventricle was diagnosed in a 47-year-old
      woman. The patient presented with hoarseness with a history of three months.
      Direct laryngoscopy performed under general anesthesia showed a large, smooth,
      gray-reddish tumor above the right vocal fold, originating from the right
      ventricle. The tumor was removed through a micro-laryngoscopic procedure with
      cold instruments. Histopathologic diagnosis was cavernous lymphangioma. There was
      no local recurrence a year after the operation.

PMID- 15493341
TI  - [Brown tumor of the maxillary sinus: a case report].
AB  - Brown tumor of the paranasal sinuses is rare. It is a benign fibro-osseous
      lesion, typically presenting as an expansile mass that leads to a cortical
      defect. We presented the radiological findings of a brown tumor of the right
      maxillary sinus in a 13-year-old boy who presented with complaints of swelling in
      the right maxillary region, headache, and epistaxis. Biochemical findings were
      compatible with primary hyperparathyroidism. The lesion was removed by partial
      parathyroidectomy. No recurrences or residual mass were detected during a six
      month follow-up period.

PMID- 15493342
TI  - [Isolated unilateral hypoglossal nerve paralysis: a report of two cases].
AB  - Two cases of unilateral isolated hypoglossal nerve paralysis are presented. One
      patient (aged 56 years, male) had a history of intubation during open cardiac
      surgery. Spontaneous clinical improvement was observed about 3.5 months after the
      onset of paralysis. In the other patient (aged 42 years, female), the onset of
      paralysis dated back 23 years before. Since no etiologic cause could be
      determined to be associated with hypoglossal nerve paralysis either at the time
      of onset or on final examinations, the case was thought to be idiopathic. No
      clinical improvement was observed during a six-month follow-up period.

PMID- 15493343
TI  - [Evaluation of quality and accessibility of health education materials. I. The
      opinion of health personnel].
AB  - The study concerning quality and accessibility of educational materials for
      health workers was taken up in 2003 in Health Promotion Department of the
      National Institute of Hygiene and Mazovian Centre of Public Health. Two
      questionnaires were elaborated: a) for physicians, b) for social-and-familial
      nurses. The questionnaire for physicians contains demographic data and questions
      about health education materials (accessibility, sufficiency, themes of received
      materials, and expectations concerning themes and forms). The questionnaire for
      social-and-familial nurses consists of demographic data and questions about
      health education materials (sources of materials, patients' concern with
      materials, adequacy for patients' interest, and needs concerning themes and
      forms). Data were obtained from 112 nurses (110 females and 2 males) working in
      Warsaw hospitals (37.6%), regional dispensaries (33.0%), specific dispensaries
      (11.9%) and other health services (19.5%). Majority of physicians (82.7%)
      answered that they received health education materials, but only 32.9% assessed
      the number as sufficient. More then seventy percents of physicians assessed, that
      materials in high degree concern advertising of pharmaceutical drugs and other
      commercial products, while only 11.3%--health promotion and healthy lifestyle,
      and 5%--disease prevention. One from three physicians needed educational
      materials for patients to give them during visits in high degree. As regards to
      themes, physicians most frequently mentioned disease prevention (41.1%), health
      promotion and healthy lifestyle (37.7%), treatment (34.9%), diet and nutrition
      (20.7%). Booklets, leaflets and posters were the forms of health education
      materials, which physicians noticed most frequently. Regarding social-and
      familial nurses, almost all (95%) received health materials from pharmaceutical
      and other commercial institutions, 68.5% from public institutions and 26.6% from
      foundations. Only one from five of the nurses assessed, that materials captured
      high interest of the patients, and 13.6% of the nurses stated, that received
      health education materials were adequate to health information needs of patients
      in high degree. Nearly the same percentage of nurses as physicians (41.4%)
      mentioned disease prevention as most desirable theme of health education
      materials, lower percentage mentioned treatment (29.5%) and health promotion and
      healthy lifestyle (19.8%). Our findings showed that most of health materials were
      received from pharmaceutical and other commercial institutions. Moreover, the
      interest to have educational materials concerning health promotion and healthy
      lifestyle is low, especially among social-and-familial nurses.

PMID- 15493344
TI  - [Evaluation of quality and accessibility of health education materials. II. The
      opinion of patients].
AB  - The study on quality and accessibility of educational materials for patients was
      taken up in Health Promotion Department of the National Institute of Hygiene and
      the Mazovian Centre of Public Health in 2003. The questionnaire contained
      demographic information (gender, age, civil state, residence, employment and
      level of education), and questions about patients' opinions concerning the
      sources of health information (usefulness for knowledge enlargement, use in
      everyday life and perceived truth). The data were obtained from 110 patients
      living in Warsaw, who waited for visit in dispensaries or had treated in
      hospitals. The patients pointed television (54.5% of respondents), members of
      family (50.9%), physician or nurse in the course of consultations (48.2%),
      journals (46.4%) and friends (43.6%) as the sources, which most frequently
      provided health information. Women significantly more frequently than men
      acquired health information from journals (respectively: 53.8% and 26.7%), while
      men more frequently than women received health information from physicians or
      nurses in course of visits (respectively: 66.7% and 41.3%). As regards to age,
      the younger patients significantly more frequently acquired health information
      from family (younger group--61.2%, medium group--37.9%, elder group - 28,2%),
      friends (respectively: 55.2%, 27.2%, 21.4%) and from educational materials
      exposed in specific dispensaries (respectively: 44.8%, 17.2%, 14.3%). The elder
      patients more frequently received health information from physicians or nurses in
      course of consultations (elder group--85.7%, medium group--62.1%, younger group-
      34.3%). In comparison with other sources, the highest percentage of respondents
      assessed health information received from physician or nurse as very useful for
      enlargement their knowledge, use in their everyday life and very true, however,
      this percentage is low (respectively: 29.0%, 25.7% and 46.7%). Our findings
      confirm the need to elaborate health education materials more adequate to
      patients' expectations.

PMID- 15493345
TI  - [Immunoaffinity columns and determination of ochratoxin A in cereals by HPLC.
      Part I.: Evaluation of extraction using methanol/water].
AB  - The method for ochratoxin A determination in cereals (wheat, rye) was described.
      Application of immunoaffinity columns (IAC) for clean-up of extracts was
      investigated. The ochratoxin A content was determined by high-performance liquid
      chromatography using C18 column and fluorimetric detection at 330 nm (excitation)
      and 460 nm (emission). The mean recovery of ochratoxin A was 65-78%. The limits
      of detection (LOD) and quantification (LOQ) were 0.015 and 0.025 microg/kg,
      respectively. The positive results were confirmed by reaction with BF3 complex in
      methanol.

PMID- 15493346
TI  - [Microbiological quality of minimally processed vegetable salads].
AB  - The microbiological condition of minimally processed vegetable salads (7-days
      durability) purchased in the retail network of Szczecin has been assessed. The
      study included 14 kinds of salads manufactured by two producers. The total count
      of mesophilic aerobic bacteria and their spores, aid-forming bacteria
      (lactobacilli), titre of coliforms, occurrence of pathogenic bacteria and counts
      of moulds and yeast were determined. No pathogenic bacteria (Salmonella,
      Staphylococcus aureus, Bacillus cereus and Proteus) was detected in all salads.
      However contamination by saprophytic microorganisms was high in salads of both
      producers. Total count of mesophilic aerobic bacteria was higher than recommended
      level (> 10(5) cfu/g) in majority of salads. The high quantities of yeast (>
      10(3) jtk/g) and lactobacilli (10(3)-10(5) fu/g) were also stated. The titre of
      coliforms was reduced (down to 0.01-0.0001 g). The count of moulds did not exceed
      100 cfu/g in a most of samples. Moulds occurring in tested samples were
      represented mainly by Penicillium sp.

PMID- 15493347
TI  - [The change in reproductive ability of male mice exposed to vinblastine and X
      rays].
AB  - The effects of male mice to vinblastine (VBL) and combined X-rays-vinblastine
      treatments on the sperm quantity and quality, fertility and induction of foetal
      deaths and congenital malformations in the offspring were investigated. VBL and
      combined X-rays-VBL exposure caused decrease in testes weight and sperm count as
      well as increased percent of abnormal spermatozoa. Both vinblastine and X-rays
      vinblastine combination induced increase in frequency of DNA single strand breaks
      in germ cells. The highest dose of VBL induced decrease of percent of pregnant
      females, decrease of live foetuses and induction of dominant lethal mutations
      after exposure some stages of spermatogenesis. Combined exposure to low doses of
      X-rays and vinblastine enhanced the frequency of dead implants. After exposure to
      VBL on its own as well as to combination of low doses of both agents increase in
      the frequency of congenital malformations was not observed.

PMID- 15493348
TI  - [Role of folates in the nutrition of the elderly].
AB  - Inadequate folate intake and in consequence deficient of plasma folate status may
      have a negative impact on human health. Among elderly the most important effects
      are related to hyperhomocysteinemia, a significant risk factor for cardiovascular
      diseases, procarcinogenic effects and cognitive dysfunctions. To prevent such
      situation and improve the quality of life of elderly people, in Poland as in many
      other countries, different strategies for increasing folate intake were applied,
      among them food fortification. At the same time it is important to educate people
      because food fortification and individual diet supplementation applied together
      could be a risk of exceeding upper level of folate intake.

PMID- 15493349
TI  - [Assessment of the nutritional value of certain molluscs].
AB  - The aim of this study was to determine levels of protein, fat, carbohydrates,
      vitamins B, as well as energy value in fish products available on domestic
      market. Nutrition value of the analyzed products was determined by analytical
      methods applying in food chemistry. Concentrations of thiamine, riboflavin,
      niacin and vitamin B6 were determined by microbiological methods. Considering
      high nutritive value, the analyzed seafood products are recommended as valuable
      ingredient of diet.

PMID- 15493350
TI  - [Dietary and life-style habits of university students in Poland--empirical
      study].
AB  - The aim of the study was the analysis of selected elements students life styles:
      nutrition behavior, physical activity, cigarettes smoking, alcohol drinking as a
      background of coronary diseases development. The respondents (412 persons) were
      university students: 339 women and 79 men. On an average they were 20 years old.
      204 persons were inhabitants of towns, 208--villages and small towns. The
      interviews were conducted in Warsaw and Olsztyn in 2002. In general, for students
      non-healthy nutrition behavior were characteristic: non-regular consumption of
      meals (about 50%)), low frequency vegetables and fruits consumption (about 50%),
      sporadic fishes consumption (about 40%), preferring butter (35%) and poor
      physical activity (about 50%). Positive aspects of students nutrition were:
      preferring of poultry (44%), high frequency of fruit juice and mineral water
      drinking (about 40%) and sporadic chips and fast-food consumption (about 80%).
      One can observe differences in regard to the place of living. Pro-healthy
      behavior were more disseminated among students living in towns. More of them
      consumed daily vegetables, fruit juices, preferred poultry, did not smoke
      cigarettes and were physically active in comparison with students living in
      villages and small towns. General conclusions: there is a necessity to create
      programmers of health education at universities.

PMID- 15493351
TI  - [Assessment of the emission of volatile organic compounds from polyurethane
      foams].
AB  - The emission of 2,4- and 2,6-diaminotoluene, triethylenediamine, diethanolamine
      and other volatile organic compounds from polyurethane foams was examined in
      environmental chamber. Tested materials did not release of amines. The emission
      of total volatile organic compounds showed differences for polyurethane samples
      but did not exceed ecological standards.

PMID- 15493352
TI  - Paclitaxel and mitoxantrone in metastatic breast cancer: a phase II trial of the
      Italian Oncology Group for Cancer Research.
AB  - BACKGROUND: In a previous dose-finding trial, in previously treated patients with
      metastatic breast cancer (MBC), we showed that the combination of Mitoxantrone
      (M) and Paclitaxel (P) may be an interesting (response rate: 69%) and well
      tolerated regimen. On the basis of these results, our group started a new trial
      in chemotherapy-naive patients with MBC. PATIENTS AND METHOD: Forty-six women
      entered in this trial, and all patients were evaluated for response and toxicity.
      Schedule of treatment was P 175 mg/m2 over 3 hr day 1 and M 12 mg/m2 day 1, every
      3 weeks. Patients were reevaluated every 3 months and chemotherapy was continued
      unless tumor progression or unacceptable toxicity occurred. RESULT: The intent-to
      treat objective response was 61% (95% confidence interval: 49%-78%). Five
      patients (11%) obtained complete response and 23 (50%) partial response with a
      median time to failure of 14 months. The median survival was 22 months (range 1
      39). The principal toxicity was hematological: 38 (82%) patients had grade 3 to 4
      leukopenia; only 2 patients had grade 4 anemia and one grade 4 thrombocytopenia.
      Nonhematological toxicity (grade 3-4) was mild and cardiotoxicity was infrequent.
      CONCLUSION: This trial suggests the combination of M and P is an active
      palliative regimen for patients with MBC. Toxicity was moderate. The infrequent
      development of cardiotoxicity suggests this combination may not share the
      problems reported with P plus doxorubicin combinations.

PMID- 15493353
TI  - Chaotic genomes make chaotic cells: the mutator phenotype theory of
      carcinogenesis applied to clinicopathological relationships of solid tumors.
AB  - Abnormalities of cell morphology and chromosomes have been identified as features
      of the pathology of tumors for more than 100 years. However, no theory of
      carcinogenesis until recently has provided a basis for relating them either to
      each other or to the clinical behavior of individual tumors in many patients. The
      mutator phenotype theory is based on large numbers of mutations occurring
      chaotically (randomly, unpredictably, and variably from cell to cell) in
      individual tumors. Chaotic mutation clearly parallels both the often-observed
      chaotic morphology of tumors and the frequently unpredictable relationship of
      these morphologies to clinical behavior. Possible implications of this concept
      for staging, grading, multifocality, and therapy of cancers are discussed.

PMID- 15493354
TI  - Phase I study of Doxil and vinorelbine in patients with advanced malignancies.
AB  - INTRODUCTION: This study was designed to define the maximum tolerated dose of
      pegylated liposomal doxorubicin (Doxil) and multiday vinorelbine (VNB), without
      and with prophylactic filgrastim, and to identify antineoplastic effect. PATIENTS
      AND METHODS: Patients with resistant cancers were treated with Doxil 50 mg/m2
      every four weeks, and with VNB 15 mg/m2 on the same day. The VNB dose escalations
      were accomplished in subsequent patient cohorts by adding VNB doses on
      consecutive days. When the maximum tolerated dose (MTD) of VNB with Doxil was
      defined, prophylactic filgrastim was added to define a second MTD. RESULTS: Of 29
      patients entered, two had early adverse events, and 27 received at least one full
      cycle with at least one month follow-up. The MTD of VNB, combined with Doxil 50
      mg/m2, was 15 mg/m2 on day 1, with neutropenia as the dose-limiting toxicity.
      With prophylactic filgrastim, the MTD was 15 mg/m2 daily for two days, with
      neutropenia and stomatitis as dose-limiting toxicities. Palmar plantar
      erythrodysesthesia occurred frequently, usually after the third cycle. Objective
      responses were documented in six patients, all of whom received multiday VNB.
      CONCLUSION: Doxil 50 mg/m2 on day 1 of a 28-day cycle can be safely combined with
      VNB 15 mg/m2 day 1, or with VNB 15 mg/m2 days 1 and 2 with filgrastim
      prophylaxis. Antineoplastic activity was observed in this heavily pretreated
      population. Future studies of Doxil 35-40 mg/m2 with multiday VNB may be
      worthwhile, especially in metastatic breast cancer.

PMID- 15493355
TI  - A phase II study of docetaxel in patients with metastatic carcinoid tumors.
AB  - Twenty-one patients with metastatic carcinoid tumors were treated with docetaxel.
      Although the treatment was well tolerated, no objective radiologic responses were
      observed. Novel, more effective agents are needed for this disease. BACKGROUND:
      Traditional combination chemotherapy regimens containing streptozocin,
      doxorubicin, and 5-fluorouracil have yielded disappointing results in patients
      with metastatic carcinoid tumors. The lack of efficacy of these combinations,
      together with their toxicity, has led to efforts to investigate therapeutic
      agents that are potentially more active and tolerable. We, therefore, assessed
      the efficacy of docetaxel in the treatment of patients with metastatic carcinoid
      tumors. METHODS: Twenty-one patients with metastatic carcinoid tumors were
      treated with docetaxel, administered at a dose of 75 mg/m2 every three weeks.
      Patients were followed for evidence of toxicity, response, and survival. RESULTS:
      Docetaxel was well tolerated in this patient population. However, no objective
      radiologic responses were noted in any of the 21 patients. Of the 13 patients who
      were evaluable for biochemical responses to therapy, four (31%) experienced
      decreases in 24-hour urinary 5-hydroxyindole acetic acid (5HIAA) excretion of
      greater than 50%. The clinical course of the patients enrolled in this study was
      marked by a high incidence of radiologically stable disease (81%), a median
      progression-free survival time of 10 months, and a median overall survival time
      of 24 months. CONCLUSION: Although treatment with docetaxel results in
      biochemical responses in patients with metastatic carcinoid tumors, the lack of
      more significant antitumor activity demonstrates the need for novel, more
      effective agents in this disease.

PMID- 15493356
TI  - Phase I trial of topotecan in combination with gemcitabine in refractory solid
      tumor patients.
AB  - PURPOSE: To determine maximum tolerated dose (MTD) and evidence of antitumor
      activity of topotecan in combination with gemcitabine in refractory cancer
      patients. METHODS: This was a Phase I, prospective, dose-escalation trial that
      employed a novel-dosing schema to investigate clinical safety. Patients were
      treated in six cohorts with topotecan (T)+gemcitabine (G). The doses of T and G
      were administered by 30-minute IV infusion, T on days one through five (0.3 mg/m2
      to 1 mg/m2) and G on days one and 15 of a 28-day cycle (1000 mg/m2 to 1500
      mg/m2). Toxicity was monitored. RESULTS: Twenty-three cancer patients were
      enrolled (colorectal, n=5; lung, n=4; gastric, n=4; esophageal, n=2; other, n=8).
      Two of three patients developed grade 3 nonhematologic toxicity attributed to
      study regimen, thereby fulfilling dose limiting toxicity requirements at cohort 6
      (T, 1 mg/m2, G, 1500 mg/m2). Maximum tolerated dose (MTD) was established at
      cohort 5 (T, 1 mg/m2, G, 1250 mg/m2). Ten patients were treated at cohort 5.
      Nonhematologic adverse effects (AEs) >grade 3 attributed to the study regimen
      were not observed. Hematologic toxicity was frequent. Twenty-five percent of
      patients in cohort 2 and 50% of patients in cohorts 4, 5, and 6 had a reduction
      of ANC to <500 mm3. All neutropenic episodes were less than one week in duration.
      Five of the patients in the last three cohorts required delay and/or dose
      reduction of G. Nineteen of 23 enrolled patients were evaluable for response. Two
      patients achieved a minimal response. CONCLUSIONS: The MTD was observed at a T
      dose of 1 mg/m2 administered on days 1 through 15, and a G dose of 1250 mg/m2
      administered on days 1 and 15 via 30 minute intravenous (IV) infusion.

PMID- 15493357
TI  - Paclitaxel and carboplatin for recurrent or persistent cancer of the cervix.
AB  - OBJECTIVE: The objective of this study was to evaluate the effectiveness and
      degree of toxicity of paclitaxel and carboplatin (PC) combination chemotherapy in
      patients with recurrent or persistent cervical carcinoma. METHODS: Fifteen
      patients who received PC chemotherapy for recurrent or persistent carcinoma of
      the cervix at the Magee-Womens Hospital from 1994-1998 were studied
      retrospectively. Demographic data, pathology, radiation treatment response, site
      of recurrence, chemotherapy response, survival rates, and toxicities were
      reviewed. Months of survival were calculated by the method of Kaplan-Meier from
      the date after initiation of chemotherapy to death or the last date of follow-up.
      RESULTS: Fifteen patients received PC for recurrence or persistence of disease
      with a median of six courses of PC (range, four to 26). Fourteen patients (93.3%)
      had received prior radiation, and one patient had received surgery as the primary
      therapy. Four (26.7%) of 15 patients had complete response and five (33.3%) had
      partial response for an overall clinical response rate of 60%. The median
      survival of all 15 patients treated with PC was 17 months (range, four to 39).
      Four patients demonstrated progression of disease while two patients had stable
      disease. Grade 3 or 4 neutropenia occurred in four patients (26.7%) while one
      patient (6.7%) suffered from sepsis. Three patients (20%) suffered from Grade 2
      anemia and four patients (26.7%) patients developed Grade 2 or Grade 3
      neuropathy. There was no incidence of nephrotoxicity. CONCLUSIONS:
      Paclitaxel/carboplatin chemotherapy appears to have promising activity in
      recurrent or persistent carcinoma of the cervix with an acceptable toxicity
      profile. Due to patient convenience and tolerance, consideration should be given
      to carboplatin as an alternative regimen to cisplatin in combination with
      paclitaxel.

PMID- 15493358
TI  - A phase II evaluation of weekly paclitaxel plus carboplatin in advanced
      urothelial cancer.
AB  - This Phase II trial was designed to evaluate the overall objective response rate,
      complete response rate, efficacy, and safety of weekly paclitaxel (Taxol) and
      carboplatin (Paraplatin) in the treatment of advanced urothelial carcinoma.
      Thirty-three patients with measurable, unresectable, stage III-IV carcinoma of
      the urothelium were enrolled. Paclitaxel (135 mg/m2) and carboplatin (AUC=2) were
      given by intravenous (IV) infusion weekly x 6 followed by two weeks rest.
      Patients were premedicated with oral dexamethasone, diphenhydramine, and
      cimetadine (or equivalent). Patient characteristics included an Eastern
      Cooperative Oncology Group Performance Status (ECOG PS) 0 (36%), one (36%), two
      (28%); median age 70 years (37-83); 29 (88%) male, four (12%) female; 16 (48%)
      patients had prior chemotherapy [eight postoperative (adjuvant), five
      neoadjuvant, three for metastatic disease] and eight (24%) had prior radiation
      therapy. Eight patients (24%) achieved objective responses, three complete
      responses (CR) and five partial responses (PR); one patient was not evaluable
      (patient died prior to first dose). The median duration of response was 13 months
      (range, 2-29). Nine patients (27%) had stable disease (SD) and 15 patients (45%)
      had progressive disease (PD). Median time to progression was 3.6 months (range, <
      1-29) and median survival was 10.3 months (range, < 1-33). Grade 3 and 4
      toxicities included: asthenia (46%), neutropenia (36%), leukopenia (15%),
      thromboembolism (12%), diarrhea (9%), nausea and vomiting (9%), hyperglycemia
      (7%), and neuropathy (6%). Two patients died of sepsis, one death was treatment
      related. Weekly paclitaxel plus carboplatin shows promising activity; however in
      the current study, efficacy may have been limited by the toxicities associated
      with this dose-intensive regimen in an elderly, pretreated patient population
      with poor performance status. This regimen warrants further study, perhaps as a
      three out of four week regimen or at reduced doses.

PMID- 15493359
TI  - A phase I trial of olanzapine (Zyprexa) for the prevention of delayed emesis in
      cancer patients: a Hoosier Oncology Group study.
AB  - Chemotherapy-induced delayed emesis (DE) can affect up to 50% to 70% of patients
      receiving moderately and highly emetogenic chemotherapy, although rates are
      improving. DE most commonly occurs within the first 24 to 48 hours of
      chemotherapy administration and can persist for 2 to 5 days. Olanzapine, due to
      its activity at multiple dopaminergic, serotonergic, muscarinic, and histaminic
      receptor sites, has potential as antiemetic therapy. A phase I study was designed
      with olanzapine, using a four-cohort dose escalation of 3 to 6 patients per
      cohort, for the prevention of DE in cancer patients receiving their first cycle
      of chemotherapy consisting of cyclophosphamide, doxorubicin, platinum, and/or
      irinotecan. All patients received standard premedication. Olanzapine was
      administered on days -2 and -1 prior to chemotherapy and continued for 8 days
      (days 0-7). Episodes of vomiting as well as daily measurements of nausea,
      sedation, and toxicity were monitored at each dose level. Fifteen patients
      completed the protocol. No grade 4 toxicities were seen, and three patients
      experienced a dose-limiting toxicity (grade 3) of a depressed level of
      consciousness during the study. The maximum tolerated dose appeared to be 5 mg
      (for days -2 and -1) and 10 mg (for days 0-7). Four of six patients receiving
      highly emetogenic chemotherapy (cisplatin, > or = 70 mg/m2) and nine of nine
      patients receiving moderately emetogenic chemotherapy (doxorubicin, > or = 50
      mg/m2) had complete control (no vomiting episodes) of DE. Therefore, olanzapine
      may be an effective agent for the prevention of chemotherapy-induced DE. A phase
      II trial is underway.

PMID- 15493360
TI  - Arsenic trioxide causes redistribution of cell cycle, caspase activation, and
      GADD expression in human colonic, breast, and pancreatic cancer cells.
AB  - Arsenic trioxide is valuable for treatment of promyelocytic leukemia, but less
      attention has been paid to its therapeutic potential for other cancers. In this
      study, the effects of arsenic trioxide were tested in human pancreatic (AsPC-1),
      colonic (HT-29), and breast (MCF-7) cancer cells. In all three cancer cell lines,
      arsenic trioxide inhibited proliferation in a concentration and time-dependent
      manner, as measured by 3H-methyl thymidine incorporation and cell counting.
      Coincident with inhibition of growth, arsenic trioxide induced marked morphologic
      changes, including reduced cytoplasmic volume, membrane blebbing, and nuclear
      condensation consistent with apoptosis. Propidium iodide DNA staining at 24 hours
      revealed cell cycle arrest in the G0/G1 phase and an increase in the S phase,
      while at 72 hr there was G2/M phase arrest with a marked increase in the sub
      G0/G1, apoptotic cell population. The DNA fragmentation induced by arsenic
      trioxide was confirmed by the terminal deoxynucleotidyl transferase-mediated
      deoxyuridine triphosphate nick-end labeling (TUNEL) assay in all cell lines.
      Western blot analysis revealed activation of caspase -3, -7, and -9 by arsenic
      trioxide. Caspase-3 activity was confirmed by demonstrating cleavage of its
      downstream target, poly ADP-ribose polymerase (PARP). Expression of the
      antiapoptosis protein, Bcl-2, was time-dependently decreased. In contrast,
      arsenic trioxide markedly enhanced the expression of the p21 protein, GADD45 and
      GADD153, in a time-dependent manner. These findings suggest that arsenic trioxide
      has potential as a therapeutic agent for these cancers.

PMID- 15493361
TI  - Case report and brief review: IL-2-induced myocarditis.
AB  - High dose bolus interleukin 2 (IL-2) used in the treatment of metastatic melanoma
      and renal cell carcinoma is known to have the potential for serious cardiac
      toxicity. At our institution 2 of 57 (3.5%) patients developed IL-2 induced
      myocarditis. The constellation of electrocardiographic changes and elevated
      troponin I is the hallmark of myocarditis. In this setting of high dose IL-2
      therapy it is important to keep myocarditis in the differential in addition to
      the more frequently sought diagnosis of acute myocardial infarction. Although the
      gold standard for diagnosis is endomyocardial biopsy, there is considerable false
      negative rate. It may be reasonable to make the diagnosis on clinical grounds,
      while providing supportive care. Future investigation is required to better
      understand the pathophysiology and what factors may influence expression of this
      toxicity.

PMID- 15493362
TI  - Dendritic cell-based immunotherapy of malignant gliomas.
AB  - The failure of conventional treatment modalities for gliomas, in spite of
      tremendous progress in research in the past two decades, has led to increasing
      interest in alternative treatment strategies, including immunotherapy. It has
      become evident that vaccination with dendritic cells (DC), designed to express
      tumor antigens, is a potent strategy to elicit anti-tumor immune response in both
      pre-clinical and clinical settings. Various methods have been applied in order to
      induce DC to express tumor antigens including: pulsing with isolated tumor
      peptides or whole tumor lysate; fusion with tumor cells; and pulsing with
      apoptotic tumor cells. Herein, we review the recent progress in DC biology with
      regard to tumor immunity and discuss current DC-based strategies and future
      prospects in immunotherapy for malignant gliomas.

PMID- 15493363
TI  - Progress in the development of immunotherapy of cancer using ex vivo-generated
      dendritic cells expressing multiple tumor antigen epitopes.
AB  - Immunotherapy with tumor-associated antigen-pulsed, ex vivo-generated dendritic
      cells (DCs) is a promising approach for the treatment of cancer that has shown
      efficacy in animal models and is now being tested in the clinic. The majority of
      studies performed to date make use of a single tumor-associated epitope. However,
      because of the high rate of mutation in tumor cells allowing for loss of
      expression of a single antigen, it is likely that use of multiple antigenic
      epitopes will induce a broader, longer-lasting, and effective tumor-specific
      immune response. Multiple vehicles for loading DCs with multiple antigenic
      epitopes are under investigation to determine the most effective method for
      vaccination, with many of these methods showing promise. These loading methods,
      as well as other critical considerations for making DC vaccination as efficacious
      as possible, are discussed in this article.

PMID- 15493364
TI  - Radical prostatectomy: status and opportunities for improving outcomes.

PMID- 15493365
TI  - Beyond hematoxylin and eosin--the role of immunohistochemistry in surgical
      pathology.
AB  - Immunohistochemistry, a technique that microscopically detects cellular
      constituents via specific antibodies, has revolutionized the field of surgical
      pathology by tremendously empowering the hematoxylin and eosin (H&E) slide. In
      the investigation of the unknown primary, it enables detecting the origin of the
      tumor by use of tissue- or organ-specific antibodies as well as antibodies
      associated with minimal histogenetic differentiation. It has almost perfected the
      pathologist's ability to make specific diagnoses such as those of mesothelioma,
      melanoma, and neuroendocrine tumors. These diagnoses should be reached by
      interpreting the immunohistochemical results in the context of a detailed
      morphological analysis and differential diagnosis based on the H&E. Other
      important uses include detection of microinvasive and micrometastatic disease.
      Through the use of prognostic markers, immunohistochemistry can provide valuable
      information regarding tumor behavior and therapy. Lastly, immunohistochemistry
      serves a small but valuable role in highlighting microorganisms, particularly
      viruses.

PMID- 15493366
TI  - Philosophical oncology: on being needed--thoughts of a deathwatcher.
AB  - The ultimate bond that connects the patient and the physician requires an
      understanding of the human drama we call illness. Medical oncology is a specialty
      filled with the uncomfortable experiences of people facing fear, anxiety, and
      loss. The caregiver must share in the distress, be troubled by the patient's
      troubles, but keep a safe distance, so as not to be wounded as well. The
      physician is not only a deathwatcher for the sickest of patients, but, by
      necessity, must be self-reflective--a doctorwatcher.

PMID- 15493367
TI  - Can we do a better job preventing clinically-relevant peripheral neuropathy
      resulting from carboplatin/paclitaxel chemotherapy?
AB  - Minor modifications in the standard "dose reduction" strategy commonly employed
      in the presence of developing carboplatin/paclitaxel-induced peripheral
      neuropathy may favorably impact the quality-of-life associated with use of this
      important combination chemotherapy regimen.

PMID- 15493368
TI  - Environmental pollutants and breast cancer.

PMID- 15493369
TI  - Chemotherapy for recurrent or persistent cervical cancer.

PMID- 15493370
TI  - Cure of glioma: a space not yet occupied for the lesion.

PMID- 15493371
TI  - Present and perspectives in prevention, diagnosis and treatment of cancer
      disease.

PMID- 15493372
TI  - Hydroalcoholic plant extracts with anti-inflammatory activity.
AB  - The aim of the present study was to investigate if standardized hydroalcoholic
      plant extracts such as Calendula officinalis, Hypericum perforatum, Plantago
      lanceolata and Glycyrrhiza glabra can suppress in cell-free systems the
      activities of 5-lipoxygenase (5-LO) and cyclooxygenase-2 (COX-2), key enzymes in
      the formation of proinflammatory eicosanoids from arachidonic acid (AA). Studies
      were undertaken to compare the above mentioned plant extracts to a known NSAID
      (nimesulide) in their ability to inhibit both cyclooxygenase (COX-2) and
      lipoxygenase (5-LO) activities in cell-free systems. We report on 2 vegetal
      extracts (Hypericum perforatum and Glycyrrhiza glabra) that inhibit 5-LO activity
      and 2 vegetal extracts (Plantago lanceolata and Glycyrrhiza glabra) that inhibit
      COX-2 activity. In this study, we demonstrate for the first time that Glycyrrhiza
      glabra extract efficiently suppresses both eicosanoids and leukotrienes formation
      in cell-free systems, implying that this extract directly acts as a dual
      inhibitor of 5-LO and COX-2 activities. With regard to the properties of dual COX
      2/5-LO inhibitors, Glycyrrhiza glabra extract might be a potential drug
      possessing anti-inflammatory activity devoid of the most troublesome (gastric)
      side effects seen for drugs used as COX-2 and 5-LO inhibitors. Hypericum
      perforatum, Plantago lanceolata and Glycyrrhiza glabra extracts can be added to
      an already impressive list of these species that have anti-inflammatory activity.

PMID- 15493373
TI  - The evolution of medically-based fitness centers.

PMID- 15493374
TI  - LifePoint pays 66% premium for Province.

PMID- 15493375
TI  - Look at hospital activity and revenue by physician specialty.

PMID- 15493376
TI  - The new era of international health care marketing for U.S. hospitals.

PMID- 15493377
TI  - Fighting obesity Part 1: Review of popular low-carb diets.

PMID- 15493378
TI  - Counseling obese patients.

PMID- 15493379
TI  - The Atkins diet.

PMID- 15493380
TI  - The Zone Diet.

PMID- 15493381
TI  - The South Beach Diet.

PMID- 15493382
TI  - The case of the felonious foxglove: the dark side of natural cures.

PMID- 15493383
TI  - Hypertension guidelines.

PMID- 15493384
TI  - Truth-telling.

PMID- 15493385
TI  - Caries prevention.

PMID- 15493386
TI  - Early caries lesions.

PMID- 15493387
TI  - Occlusion confusion.

PMID- 15493388
TI  - Techniques for reducing anesthetic injection pain: an interdisciplinary survey of
      knowledge and application.
AB  - BACKGROUND: The authors conducted a study that considered family physicians' and
      dentists' knowledge and application of techniques to reduce the pain associated
      with anesthetic injections. They also assessed practitioners' discomfort with
      patients' injection pain and needle anxiety/phobia. METHODS: The authors designed
      a questionnaire about awareness and use of 10 techniques for reducing pain of
      anesthetic injection and mailed it to 2,000 randomly selected family physicians
      and general dentists. They analyzed the data to examine differences between
      disciplines regarding awareness and use of techniques, reasons for not using
      techniques, number of injections given per week, and predictive value of certain
      demographic variables on reported use of individual techniques and on
      practitioner reactions to patients' pain and anxiety. RESULTS: The response rate
      was 35 percent. The authors used the chi2 test for differences between
      disciplines' awareness of and use or nonuse of techniques, Wilcoxon testing to
      assess differences between disciplines' median values of number of weekly
      injections and logistic regression to study demographic variables' predictive
      values (P = .01). General dentists give more injections than do family
      physicians. Differences existed between disciplines' awareness and use of eight
      of 10 techniques. Disciplines reported cost and time issues as reasons for not
      using some techniques. Number of years in practice and age were associated with
      use of six techniques. Dentists reported feeling greater personal effects of
      patients' pain and needle anxiety/phobia than did family physicians. CONCLUSIONS:
      Those not using pain-lessening techniques inaccurately identified time and cost
      as problems, suggesting that respondents may be less familiar with these
      techniques than otherwise reported. Further study is recommended. CLINICAL
      IMPLICATIONS: Pain reduction techniques for anesthetic injection cost little to
      implement, are not time liabilities, and can lessen avoidable pain and reduce the
      incidence of needle phobia.

PMID- 15493389
TI  - Trends in dental and allied dental education.
AB  - BACKGROUND: Educational programs play an important role in preparing a qualified
      dental work force. This article reviews the current status and trends in dental,
      advanced dental and allied dental education programs in the United States and
      examines their impact on the dental work force. OVERVIEW: This analysis focuses
      on survey data collected by the American Dental Association during the past 10 to
      15 years and compares recent patterns in applications, enrollment and graduation
      with previous trends. The numbers of educational programs, applicants, enrollees
      and graduates have increased in dentistry, dental hygiene and dental assisting,
      while dental laboratory technology has declined in all measures. The proportion
      of women in dentistry has increased, while the ethnic profile of dental and
      allied personnel has shown little change. Both the cost of dental education and
      student debt continue to increase. CONCLUSIONS: Despite increases in the number
      of educational programs and overall numbers of graduates from dental and allied
      dental education programs, the proportion of underrepresented groups still lags
      behind their representation in the overall population, and the number of allied
      personnel falls short of practice needs. PRACTICE IMPLICATIONS: Patterns in
      applications, enrollment and graduation are important determinants of the dental
      and allied dental work force. The cost and funding of education significantly
      affect the attractiveness of dental careers and the sustainability of educational
      programs and should be monitored carefully by the profession.

PMID- 15493390
TI  - The American Dental Association's oral cancer campaign: the impact on consumers
      and dentists.
AB  - BACKGROUND: The ADA conducted a public service campaign in late 2001 to raise
      awareness of oral cancer and of the dentist's role in early detection. METHODS:
      To gather information about the impact of this campaign, the ADA undertook two
      surveys. A telephone survey was conducted among 1,270 adult consumers, and a
      second survey was mailed to a national sample of 2,500 dentists. RESULTS: The
      majority of the consumers did not recognize the fact that dentists are
      responsible for examining their patients for oral cancer and that oral cancer
      claims more lives than melanoma or cervical cancer. The majority of dentists was
      aware of the ADA campaign and agreed that it helped raise the public's awareness
      of oral cancer and the importance of early detection. As a result, more dentists
      said that they are likely to educate their patients about early detection, adjust
      their own practice routines to include discussion about the disease, and look
      more closely for small oral lesions and test them with the brush biopsy test.
      CONCLUSIONS: The results of the survey of dentists demonstrated that the oral
      cancer awareness initiative sponsored by the ADA resulted in positive behavioral
      changes targeted toward the early detection of oral cancer. CLINICAL
      IMPLICATIONS: Continued efforts to provide health education and health promotion
      interventions aimed at consumers and dentists invariably will result in the
      detection of oral cancers at early and curable stages.

PMID- 15493391
TI  - Anesthetic efficacy of the palatal-anterior superior alveolar injection.
AB  - BACKGROUND: A single palatal-anterior superior alveolar, or P-ASA, injection has
      been reported to provide pulpal anesthesia of the four maxillary incisors and
      usually the canines. The authors conducted a prospective, randomized, double
      blind study to compare the anesthetic efficacy of 2 percent lidocaine with
      1:100,000 epinephrine and 3 percent mepivacaine using a computer-assisted
      injection system to administer the P-ASA injection. MATERIALS AND METHODS: In a
      double-blind manner, the authors used a crossover design to administer randomly P
      ASA injections of 1.4 milliliters of the lidocaine solution and 1.4 mL of the
      mepivacaine solution using the computer-assisted injection system at two
      appointments to 40 subjects. They used a pulp tester to test for anesthesia of
      the central incisors, lateral incisors and canines in four-minute cycles for 72
      minutes. Anesthesia was considered successful when two consecutive maximum
      readings (80 readings) with the pulp tester were obtained. RESULTS: For the
      lidocaine solution, successful pulpal anesthesia ranged from 32 to 58 percent for
      the six anterior teeth. For the mepivacaine solution, successful pulpal
      anesthesia ranged from 22 to 38 percent. Except for the left canine, the
      lidocaine solution was significantly more likely to result in pulpal anesthesia
      than the use of the mepivacaine solution. The duration of pulpal anesthesia, for
      both solutions, declined steadily over 72 minutes. CONCLUSIONS AND CLINICAL
      IMPLICATIONS: Using the computer-assisted injection system for the P-ASA
      injection, we concluded that the rather modest-to-low success rates of the
      lidocaine and mepivacaine solutions would not ensure predictable pulpal
      anesthesia of the four maxillary incisors and the canines.

PMID- 15493392
TI  - The prevalence of oral mucosal lesions in U.S. adults: data from the Third
      National Health and Nutrition Examination Survey, 1988-1994.
AB  - BACKGROUND: Most reports of oral lesion prevalence are based on studies of
      atypical populations. There are no published studies on oral mucosal lesion
      prevalence in U.S. adults that are based on a national probability sample.
      METHODS: The Third National Health and Nutrition Examination Survey, or NHANES
      III, employed a complex, multistage sample of 33,994 civilian,
      noninstitutionalized people from 19,528 households. Dentist examiners were
      trained to recognize, classify and record in a standardized manner the clinical
      characteristics of each of the 48 conditions of interest to include diagnosis,
      size, location, surface morphology, color consistency, pain, duration and history
      using procedures based on the World Health Organization's Guide to Epidemiology
      and Diagnosis of Oral Mucosal Diseases. RESULTS: Examinations were performed on
      17,235 people aged 17 years and older, of whom 4,801 (27.9 percent) had a total
      of 6,003 lesions. Denture-related lesions (stomatitis, hyperplasia, ulcers,
      inflammation and angular cheilitis) composed 8.4 percent and tobacco-related
      lesions (smokeless tobacco-related and nicotinic stomatitis) composed 4.7 percent
      of all lesions. Discounting denture-related lesions, amalgam tattoos were the
      most prevalent lesions (3.30 percent), followed closely by cheek/lip bites (3.05
      percent) and frictional white lesions (2.67 percent). Smokeless-tobacco users
      (odds ratio, or OR, = 3.90) and removable denture wearers (OR = 3.57) had the
      highest odds of having a lesion. CONCLUSION: Lesion prevalences differed
      significantly by age, sex, race/ethnicity, denture wearing and tobacco use. When
      lesion-specific prevalences are cited in the literature, they should be
      stratified by covariates known to be associated with them.

PMID- 15493393
TI  - Aspiration and ingestion in dental practice: a 10-year institutional review.
AB  - BACKGROUND: This article is an institutional retrospective review of incidents
      involving aspiration and ingestion of dental foreign objects at a large
      multidisciplinary dental educational facility. It was undertaken to determine
      which dental procedures were more likely to involve aspiration or ingestion, as
      well as to evaluate the outcome of these adverse incidents. METHODS: The
      inclusion criteria involved all patients who were documented to have experienced
      loss of dental instruments or material behind the posterior pharynx during a 10
      year consecutive period. The dental and medical records of these patients were
      analyzed, and the outcomes of the adverse events fell into three categories:
      aspiration, ingestion, or neither aspirated nor ingested. The authors also noted
      the type of dental instrument and the specialty or area of dentistry in which
      this event occurred. RESULTS: There were 36 documented cases. Twenty-five of
      these were instances of ingestion and one was an aspiration. In 10 cases,
      aspiration and ingestion were ruled out through radiographic examination or the
      object was retrieved from the patient's mouth. CONCLUSIONS: Fixed prosthodontic
      therapy had the highest number of incidents of adverse outcomes. Ingestion was a
      more prevalent outcome than aspiration. Dental procedures involving single-tooth
      cast or prefabricated restorations involving cementation have a higher likelihood
      of aspiration. CLINICAL IMPLICATIONS: The implications for clinical practice
      include the recognition of risk that dental therapy demands in regard to the
      airway and posterior pharynx, documentation and follow-up of adverse outcomes,
      and the use of preventive measures such as rubber dams or gauze throat screens or
      floss ligatures.

PMID- 15493394
TI  - Severe acute respiratory syndrome and dentistry: a retrospective view.
AB  - BACKGROUND: Severe acute respiratory syndrome, or SARS, which has created panic
      in Asia and in some parts of North America, is the first epidemic of the new
      century. Although it has been well-contained, sporadic cases continue to emerge.
      OBJECTIVES: The authors trace the emergence of the SARS outbreak from southern
      China and its spread worldwide, discuss the viral etiology of the infection and
      its clinical features, and review the infection control guidelines issued during
      the outbreak by the health authorities in Hong Kong, the Centers for Disease
      Control and Prevention, the World Health Organization and the American Dental
      Association. They also review the prospects for a new outbreak and preventive
      measures. OVERVIEW: The disease, which is caused by a novel coronavirus termed
      the "SARS coronavirus," or SARS-CoV, essentially spreads through droplet
      infection and affects people of any age. It has a mortality rate ranging from 10
      to 15 percent. A major hallmark of this disease has been the rate at which it has
      affected health care workers through nosocomial transmission; in some countries,
      up to one-fourth to one-third of those infected were in this category. However,
      no dental health care worker has been affected by SARS in a nosocomial or dental
      setting. CONCLUSIONS AND CLINICAL IMPLICATIONS: Researchers believe that a
      combination of factors, including the universal infection control measures that
      the dental community has implemented and/or the low degree of viral shedding in
      the prodromal phase of SARS, may have obviated the spread of the disease in
      dental settings. The dental community should reflect on this outbreak to
      reinforce the currently applied infection control measures.

PMID- 15493395
TI  - Post concepts are changing.
AB  - Use of post-and-core restorations has changed markedly in the past several
      decades. Current use and research supports techniques using tooth-colored, fiber
      reinforced resin-based composite posts or titanium alloy posts cemented with
      resin cement, followed by resin-based composite build-ups. Although fiber
      reinforced resin-based composite posts appear to be very promising, long-term
      clinical observation is needed. I have made suggestions about when to use posts,
      what type of post to use and how to use them.

PMID- 15493396
TI  - The efficacy of valacyclovir in preventing recurrent herpes simplex virus
      infections associated with dental procedures.
AB  - BACKGROUND: Oral herpes simplex virus, or HSV, infections recur after trauma and
      stress. The prevalence of these infections after dental procedures is not known.
      Also, it is unclear whether antiviral agents are effective in preventing dental
      procedure-induced HSV recurrences. This study determined the efficacy and safety
      of oral valacyclovir in suppressing dentally related cold sore outbreak and HSV
      shedding. METHODS: The authors enrolled 125 otherwise healthy HSV-seropositive
      adults who reported having recurrent herpes labialis (more than one episode per
      year and at least one episode in the previous year) in a randomized, double
      blind, placebo-controlled study and gave them valacyclovir prophylactically (2
      grams taken twice on the day of dental treatment and 1 g taken twice the next
      day) or a matching placebo. To detect the presence of the virus, the authors used
      clinical examinations, viral cultures and real-time polymerase chain reaction
      analysis of saliva. RESULTS: During the one-week observation period after
      treatment, there were more clinical lesions (20.6 percent versus 11.3 percent),
      more HSV-1-positive culture specimens (7.9 percent versus 1.6 percent) and more
      HSV-1-positive saliva specimens (7.9 percent versus 4.0 percent) in placebo than
      in valacyclovir-treated patients, respectively. The percentage of patients who
      developed recurrences and shed HSV-1 in saliva 72 hours after dental procedures
      was significantly smaller in the valacyclovir group than in the placebo group
      (11.3 percent versus 27 percent; P = .026). The mean time to pain cessation was
      significantly less in the valacyclovir group (3.2 days) than in the placebo group
      (6.2 days) (P = .006). CONCLUSION: HSV recrudescence after routine dental
      treatment is suppressed by valacyclovir prophylaxis. CLINICAL IMPLICATIONS: HSV
      recrudescence is common after routine dental treatment. Clinicians should
      consider antiviral therapy for patients at risk of experiencing a recurrence, as
      well as to minimize transmission of the disease.

PMID- 15493397
TI  - Inventory control.
AB  - By establishing clear inventory ordering targets and following the guidelines
      outlined in this column, the staff member handling the process will understand
      the high and low levels of inventory control and be able to maintain an accurate
      system. Inventory control represents approximately 6 to 8 percent of practice
      purchasing. The main goal of the advice in this column is not to reduce the cost,
      unless there is waste involved, but rather to establish a process that allows the
      practice to purchase supplies on a regular basis, avoid mistakes and maintain a
      steady expense level.

PMID- 15493398
TI  - The second 'D.D.S.' degree: a formula for practice success.
AB  - BACKGROUND: Planning for success is critical in clinical dentistry and in the
      management of a dental practice. Dentists need to apply basic business principles
      to planning their dental careers as they develop a vision, deliver quality
      products and services, and surpass patients,' staff members' and their own
      expectations. CONCLUSIONS: By applying general business management principles,
      dental practices can develop a logical, systematic approach to the management of
      a professional services business. For many dental professionals, these concepts
      were not learned in an undergraduate dental educational program and need to be
      mastered after professional school. PRACTICE IMPLICATIONS: Ideally, each dentist
      will establish a philosophical course that provides direction to the practice of
      dentistry. For a private dental practitioner, part of his or her goal is to
      create a tangible, transferable asset and a solid business plan that can benefit
      the practitioner in the present, as well as in the future practice transition.

PMID- 15493399
TI  - Licensing boards confront sexual misconduct: consent may not be a defense.

PMID- 15493400
TI  - For the dental patient. Careers in dentistry: learn more about dental laboratory
      technology.

PMID- 15493401
TI  - Beyond transition: a comparison of the employment experiences of American and
      Canadian adults with LD.
AB  - With the passage of the Americans with Disabilities Act in the United States and
      the Canadian Chartre of Rights and Freedoms, there is a new work environment for
      individuals with learning disabilities (LD) in North America. This qualitative
      study sought to compare the employment experiences of 25 U.S. adults with LD and
      24 Canadian adults with LD. Areas of comparison were job getting, experiences on
      the job, and job advancement. Remarkably, the U.S. and Canadian adults with LD
      had nearly the same employment experiences. In essence, each set of data mirrored
      the other despite marked differences in U.S. and Canadian federal disability
      legislation.

PMID- 15493402
TI  - Responsiveness to mathematical problem-solving instruction: comparing students at
      risk of mathematics disability with and without risk of reading disability.
AB  - This study assessed responsiveness to a 16-week mathematical problem-solving
      treatment as a function of students' risk for disability. Among 301 third
      graders, TerraNova scores were used to categorize students as at risk for both
      reading and mathematics disability (MDR/RDR; 20 control and 12 experimental), at
      risk for mathematics disability only (MDR-only; 5 and 8), at risk for reading
      disability only (RDR-only; 12 and 15), or not at risk (NDR; 60 and 69).
      Interactions among at-risk status, treatment, and time showed that as a function
      of treatment, MDR/RDR, MDR-only, and RDR-only students improved less than NDR
      students on computation and labeling, and MDR/RDR students improved less than all
      other groups on conceptual underpinnings. Exploratory regressions suggested that
      MDR/RDR students' math deficits or their underlying mechanisms explained a
      greater proportion of variance in responsiveness to problem-solving treatment
      than reading deficits or their underlying mechanisms.

PMID- 15493403
TI  - Season of birth is related to child retention rates, achievement, and rate of
      diagnosis of specific LD.
AB  - A sizable literature has demonstrated that the achievement of children in early
      elementary school is related to their season of birth: Those born in summer
      typically perform less well than those born in the fall. A small literature
      indicates that more children diagnosed with specific learning disabilities (SLD)
      are born in the summer. We have begun to explore the possibility that the same
      processes may account for both outcomes. In order to better understand these
      processes, the standardized achievement levels and rates of diagnosis of SLD for
      children born during each season were studied in one geographical area of the
      State of Georgia served by 28 school districts. Standardized achievement scores
      in reading, mathematics, and science were reliably lower for those born in the
      summer. Furthermore, there was a strong relationship between season of birth and
      the rate at which children received a diagnosis of SLD. Summer-born children were
      diagnosed with SLD at a higher rate than their peers. Four hypotheses for both
      the lower performance in the general school population and the greater rate of
      SLD diagnosis among these children are discussed.

PMID- 15493404
TI  - Decision making in determining eligibility of culturally and linguistically
      diverse learners: Reasons given by assessment personnel.
AB  - Assessment personnel from the southern borderlands area of Texas participated in
      analyzing one of four different hypothetical cases. Respondents were expected to
      defer making eligibility decisions due to language proficiency, environment,
      culture, or lack of data. When data were lacking, the investigators proposed that
      respondents would recognize the need for additional information and defer making
      a decision. Differences in eligibility decisions were found when the respondents
      analyzed cases in which a significant discrepancy existed and in cases in which
      language proficiency information was provided. Experience in assessment was
      significant in the determination that additional information was needed to reach
      a decision, F(2, 87) = 3.99, p < .05. A majority of the respondents (83%) made an
      eligibility decision using insufficient data.

PMID- 15493405
TI  - Graphosyllabic analysis helps adolescent struggling readers read and spell words.
AB  - Adolescents with word-reading skills below grade level were randomly assigned to
      one of three conditions. Those receiving interventions practiced reading 100
      multisyllabic words, either by analyzing graphosyllabic units in the words or by
      reading the words as unanalyzed wholes. The third group received no special
      instruction. Posttests revealed that graphosyllabic instruction helped students
      to decode novel words, remember how to read words with practice, and remember the
      spellings of words when compared to controls. In contrast, whole-word instruction
      yielded no benefit on transfer tasks compared to controls. Effects were observed
      primarily among adolescents reading at a third-grade-equivalent level and less so
      at a fourth- and fifth-grade-equivalent level. Results are consistent with a
      connectionist view of word learning and indicate the importance of providing
      struggling readers with instruction and practice in how to fully analyze the
      graphosyllabic constituents of words.

PMID- 15493406
TI  - Specific impairment in developmental reading disabilities: a working memory
      approach.
AB  - Children with developmental reading disabilities (RD) frequently display impaired
      working memory functioning. However, research has been divergent regarding the
      characteristics of the deficit. Our investigation addressed this controversy by
      assessing Baddeley's working memory model as a whole rather than focusing on
      particular aspects of it, as has been done by much of the research to date.
      Participants included 20 children with RD and 20 typical readers between the ages
      of 9 and 13. The phonological loop, visual-spatial sketchpad, and central
      executive were assessed according to Baddeley's model. The results demonstrated
      that children with RD have an impaired phonological loop but intact visual
      spatial sketchpad and central executive functioning as compared to controls. In
      terms of the phonological loop, the deficit appears to be specific to the
      phonological store. Furthermore, our research supports a relationship between
      phonological processing and phonological loop functioning.

PMID- 15493407
TI  - [Acute coronary syndrome, stroke, arterial occlusive disease. Bring the patients
      out of the danger zone!].

PMID- 15493408
TI  - [Attack on many vascular fronts. Atherothrombosis trouble seldom comes alone].

PMID- 15493409
TI  - [Patients with arterial occlusive disease die of myocardial infarct or stroke.
      The dangerous sisters: arterial occlusive disease and coronary heart disease].

PMID- 15493410
TI  - [Arterial occlusive disease as marker illness--interview with Prof. Dr. Curt
      Diehm. Discover the "silent majority"!].

PMID- 15493411
TI  - [Combination is standard. Dual thrombocyte function inhibition in acute coronary
      syndrome].

PMID- 15493412
TI  - [Interview with Prof. Dr. H. J. Rupprecht about secondary prevention: what is the
      optimal thrombocyte function inhibition?].

PMID- 15493413
TI  - [Secondary prevention after ischemic stroke. High risk patients need special
      protection].

PMID- 15493414
TI  - [Primary and secondary prevention of stroke. Prevention is better than healing].

PMID- 15493415
TI  - [Mixed germ cell tumours of the ovary in childhood and adolescence].
AB  - Mixed germ cell tumours of the ovary are rare malignant neoplasms containing
      combinations of two or more types of germ cell elements. The aim of the study was
      to review biopsy examinations, medical records, treatment strategy, follow-up and
      outcome of all girls treated for mixed germ cell tumour of the ovary at the
      Department of Pediatric Oncology, University Hospital Motol during the period
      1979-2002. Archival slides of all tumours were reviewed and tumours were
      classified according to the WHO system. The clinical data on surgical treatment,
      chemotherapy and radiotherapy used and follow-up information were obtained in all
      girls. The staging was reviewed retrospectively on the basis of surgical and
      pathological findings and results of imaging investigations, and it was outlined
      according to the most recent FIGO criteria and TNM classification. Sixteen girls
      with mixed germ cell tumour of the ovary, age range 3 years 11 months to 17 years
      8 months (median 12 years) were treated. All girls presented with unilateral
      tumour of the ovary and all underwent surgery as an initial treatment. The most
      common presenting symptom was abdominal pain, occurring in ten patients. The
      original diagnosis of mixed histology was confirmed in all cases; in five cases
      the tumour contained three histologic components, in eleven cases the tumour
      consisted of two germ cell types. All tumours contained elements of yolk sac
      tumour, followed by immature teratoma, embryonal carcinoma, dysgerminoma and
      mature teratoma. At the time of diagnosis three patients had stage I disease,
      four patients stage II, seven stage III and two stage IV disease. All patients
      were treated with chemotherapy after surgery, predominantly with platinum-based
      regimens (PVB, BEP). Three patients treated initially with MAC (metothrexate,
      dactinomycin, cyclophosphamide) were diagnosed in the early eighties. In seven
      girls with advanced disease treated in the early years, radiotherapy was
      administered to the pelvis or whole abdomen. Overall survival and event-free
      survival were 80% and 81.3% respectively (median follow-up time 7.6 years). Three
      patients have died from the disease, two progressed on treatment (MAC), one girl
      relapsed three months after finishing therapy, no further therapy was
      administered. One girl underwent resection of tumour of her remaining ovary 24
      months after original diagnosis. Histology showed mixed serous and mucinous
      cystadenoma. The latest examinations revealed that all other patients were in
      good health. Microscopic examination should be extensive and careful to find out
      all types of malignant germ cell elements. Platinum based chemotherapy is
      effective in the management of children and adolescents with mixed germ cell
      tumors of the ovary. Chemosensitivity of these tumours allows most girls to have
      conservative surgery with possible preservation of reproductive function.

PMID- 15493416
TI  - [What is your diagnosis? Answer: Subcutaneous myxopapillary ependymoma in the
      sacrococcygeal area].

PMID- 15493417
TI  - [Oncocytic adrenocortical neoplasms].
AB  - Oncocytic neoplasms of the adrenal gland are rare, as described in literature.
      Only 27 cases have been reported up to now in world literature. Here we describe
      our experience. In this report we discuss the clinicopathologic and
      immunohistochemical findings of three oncocytic tumors of the adrenal cortex. Two
      tumors were found during examination of the patients for other reasons. These
      tumors were hormonally inactive. One tumor manifested by the virilization of the
      patient. Immunohistochemical examination demonstrated in all tumors focal
      positivity with antibodies to neuron-specific enolase and synaptophysin and
      mostly focally weak positivity for cytokeratins. Very low mitotic activity was
      found in two tumors. Criteria for evaluation of biological character of this type
      of tumors are not established.

PMID- 15493418
TI  - [Solitary fibrous tumor of the pleura--description of two cases with features of
      malignancy].
AB  - Two cases of solitary fibrous tumor of the pleura with features of malignancy are
      described. In the first case, the tumor macroscopically showed noncircumscribed
      growth. Microscopically, on low power examination, the tumor was
      characteristically "patternless", with alternation of cellular areas and
      hypocellular, prominently collagenized areas. There was an infiltrative growth
      present at the margins. Cytological atypias were not present. In the second case,
      the tumor was macroscopically circumscribed. Microscopically, on low power
      examination, the tumor had characteristical "patternless" appearance again.
      Pleomorphic cells with high mitotic activity dominated in cellular areas on high
      power examination. The infiltrative pattern of growth was not present at the
      margins. Both tumors were classified as malignant solitary fibrous tumors of the
      pleura, or fibrosarcomas of the pleura. The criteria of malignancy for solitary
      fibrous tumor are discussed.

PMID- 15493419
TI  - Squamous cell carcinoma in situ involving mesonephric remnants of the uterine
      cervix.
AB  - Squamous cell carcinoma in situ (CIS) involving mesonephric remnants of the
      uterine cervix is a very rare lesion, the existence of which is still
      controversial. A second case of this lesion is reported. It was found in a cone
      biopsy specimen from an 40-year-old patient. Besides, in surface epithelium and
      within cervical glands, a structure of CIS was seen in conjunction with
      mesonephric tubules in deeper cervical stroma. The mesonephric nature of these
      tubules and of tubule-appearing epithelium within islands of CIS was supported by
      immunohistochemical positivity for CD10 and vimentin. The lesion strongly
      simulated invasive carcinomas, such as adenosquamous carcinoma and adenoid basal
      carcinoma (epithelioma) of the cervix.

PMID- 15493420
TI  - [Papillary renal cell carcinoma surrounded by unusual fibrotic reaction
      resembling inflammatory pseudotumour--a case report].
AB  - Authors report clinicopathological features of an unusual case of composite renal
      lesion occuring in 32-year-old Caucasian male. The patient was followed for
      cystic lesion of retroperitoneal-renal region for 5 years. He was indicated for
      resection of the cystic lesion because of changes of the retroperitoneal mass on
      CT scan. A cyst was located on upper renal pole. A huge cystic mass filled mainly
      by necrotic material was resected and submitted for histological examination. The
      wall of the cyst was composed of fibrous tissue, indistinguishable from
      inflammatory pseudotumor on histological level. The vital intracystic tissue was
      formed by well-differentiated papillary renal cell carcinoma. The most important
      step within differential diagnosis is distinguishing of sarcomatoid
      differentiation in renal cell carcinoma. This very rare case demonstrates the
      importance of careful examination of all spindle cell lesions of the kidney.

PMID- 15493421
TI  - Intestinal spirochaetosis: a rare histopathological diagnosis and potential light
      microscopic pitfall.
AB  - A case of intestinal spirochaetosis is described. Endoscopic specimens of a 52
      year-old female revealed a blue basophilic margin of mucosal surface in
      haematoxylin-eosin stained sections. However, on ultrastructural level, moderate
      infestation of enterocytic brush border with spirochaetes was found. The pitfalls
      of histopathological diagnosis of spirochaetosis are discussed.

PMID- 15493423
TI  - [Christian faith and autopsy].

PMID- 15493422
TI  - [Cavernous hemangioma of the heart as an incidental finding during autopsy].
AB  - During autopsy of a 72-year-old woman a cavernous hemangioma of the heart was
      found. It was 10 mm in diameter, situated subepicardially in the sulcus
      coronarius in neighbourhood of the right coronary artery. The problematics of
      hemangiomas in the context of benign heart tumors is discussed.

PMID- 15493424
TI  - [The problematics of autopsy in Czech law].

PMID- 15493425
TI  - [Pathologic anatomists--authors].

PMID- 15493426
TI  - For which students with learning disabilities are self-concept interventions
      effective?
AB  - We have previously conducted a meta-analysis of outcomes of school-based
      interventions aimed at enhancing the self-concept of students with learning
      disabilities (LD). This study extends the previous findings by analyzing
      intervention effect sizes in relation to students' levels of self-concept prior
      to intervention. The results of these analyses indicated that only groups of
      students with documented low self-concept benefited significantly from
      intervention. For these students, intervention effects were much larger than the
      effects previously estimated from aggregations that included groups with wide
      ranging or unknown levels of self-concept prior to intervention. These findings
      underscore the need for researchers and practitioners to identify students for
      self-concept intervention based on their documented need, rather than assuming a
      need based on the students' identification as students with LD.

PMID- 15493427
TI  - Teaching expressive writing to students with learning disabilities: research
      based applications and examples.
AB  - This article presents research-based examples of effective instructional
      approaches for improving the quality of the content of stories and essays written
      by students with learning disabilities. We also describe recent research on
      handwriting and spelling (transcription skills) and show how instruction in these
      areas affects overall writing quality. Examples of instructional approaches that
      improve writing quality are taken from experimental studies included in a recent
      meta-analysis by Gersten and Baker (2001) conducted on writing intervention
      research. A common goal in these studies was to teach students with learning
      disabilities how to organize writing tasks, generate ideas about the writing
      topics, and produce final written products that were coherent and organized. In
      this article, our goal is to illustrate how findings from these studies can be
      implemented in both general and special education settings.

PMID- 15493428
TI  - Instructing adolescents with learning disabilities: converting a meta-analysis to
      practice.
AB  - A previous meta-analysis indicated that eight instructional factors--Questioning,
      Sequencing and Segmentation, Skill Modeling, Organization and Explicit Practice,
      Small-Group Setting, Indirect Teacher Activities (e.g., homework), Technology,
      and Scaffolding-captured the majority of successful intervention programs for
      adolescents with learning disabilities (LD). Most important was the
      Organization/Explicit factor, which contributed significant variance (16%) to
      effect size. This factor included two important instructional components: advance
      organization and explicit practice. In this article, we convert these findings
      into practical guidelines to direct instructional practice.

PMID- 15493429
TI  - Writing instruction in kindergarten: examining an emerging area of research for
      children with writing and reading difficulties.
AB  - This review examines the literature on how to teach kindergarten children with
      reading and writing difficulties how to write. Specifically, research on
      handwriting instruction, spelling instruction, and composition writing is
      discussed. Due to the limited number of empirical studies on writing that
      included kindergarten students with diagnosed reading and writing difficulties,
      selected studies conducted with the full range of kindergarten children, as well
      as studies conducted in the early elementary grades, are presented to highlight
      future directions for research.

PMID- 15493430
TI  - Subgrouping poor readers on the basis of individual differences in reading
      related abilities.
AB  - The present study investigated the use of the Reading Component Model to subgroup
      poor readers. A large sample of poor readers was identified in second grade and
      subgrouped on the basis of relative strengths and weaknesses in word recognition
      and listening comprehension. Although homogeneous subgroups were not identified,
      poor readers could be classified into four subgroups that differed significantly
      in reading-related abilities. Further analyses showed that poor readers'
      strengths and weaknesses in listening comprehension, and to a lesser extent in
      word recognition, were foreshadowed by their abilities on related kindergarten
      measures. Follow-up testing in the fourth grade indicated that poor readers'
      individual differences in word recognition and listening comprehension were
      consistent and that subgroups were moderately stable. The implications of these
      results for the assessment and remediation of reading disabilities are discussed.

PMID- 15493431
TI  - Sensory, cognitive, and linguistic factors in the early academic performance of
      elementary school children: The Benton-IU project.
AB  - Standardized sensory, perceptual, linguistic, intellectual, and cognitive tests
      were administered to 470 children, approximately 96% of the students entering the
      first grade in the four elementary schools of Benton County, Indiana, over a 3
      year period (1995--1997). The results of 36 tests and subtests administered to
      entering first graders were well described by a 4-factor solution. These factors
      and the tests that loaded most heavily on them were reading-related skills
      (phonological awareness, letter and word identification); visual cognition
      (visual perceptual abilities, spatial perception, visual memory); verbal
      cognition (language development, vocabulary, verbal concepts); and speech
      processing (the ability to understand speech under difficult listening
      conditions). A cluster analysis identified 9 groups of children, each with a
      different profile of scores on the 4 factors. Within these groups, the proportion
      of students with unsatisfactory reading achievement in the first 2 years of
      elementary school (as reflected in teacher-assigned grades) varied from 3% to
      40%. The profiles of factor scores demonstrated the primary influence of the
      reading-related skills factor on reading achievement and also on other areas of
      academic performance. The second strongest predictor of reading and mathematics
      grades was the visual cognition factor, followed by the verbal cognition factor.
      The speech processing factor was the weakest predictor of academic achievement,
      accounting for less than 1% of the variance in reading achievement. This project
      was a collaborative effort of the Benton Community School Corporation and a
      multidisciplinary group of investigators from Indiana University.

PMID- 15493432
TI  - Effect size use in studies of learning disabilities.
AB  - The misinterpretation and overuse of significance testing in the social sciences
      has been widely criticized. This criticism is reviewed, along with several
      recommendations found in the literature, including the use of effect size
      measures to enhance the interpretation of significance testing. A review of
      typical effect size measures and their application is followed by an analysis of
      the extent to which effect size measures have been applied in three prominent
      journals on learning disabilities over a 10-year period. Specific recommendations
      are offered for using effect size measures to improve the quality of reporting on
      quantitative research in the field of learning disabilities.

PMID- 15493433
TI  - Toward a research-based assessment of dyslexia: using cognitive measures to
      identify reading disabilities.
AB  - One hundred five participants from a random sample of elementary and middle
      school children completed measures of reading achievement and cognitive abilities
      presumed, based on a synthesis of current dyslexia research, to underlie reading.
      Factor analyses of these cognitive variables (including auditory processing,
      phonological awareness, short-term auditory memory, visual memory, rapid
      automatized naming, and visual processing speed) produced three empirically and
      theoretically derived factors (auditory processing, visual processing/speed, and
      memory), each of which contributed to the prediction of reading and spelling
      skills. Factor scores from the three factors combined predicted 85% of the
      variance associated with letter/sight word naming, 70% of the variance associated
      with reading comprehension, 73% for spelling, and 61% for phonetic decoding. The
      auditory processing factor was the strongest predictor, accounting for 27% to 43%
      of the variance across the different achievement areas. The results provide
      practitioner and researcher with theoretical and empirical support for the
      inclusion of measures of the three factors, in addition to specific measures of
      reading achievement, in a standardized assessment of dyslexia. Guidelines for a
      thorough, research-based assessment are provided.

PMID- 15493434
TI  - The wide attentional window: a major deficit of children with attention
      difficulties.
AB  - The present study assessed visual selective attention in children with attention
      difficulties compared to age-matched, typically achieving children. We used the
      flanker task, which requires participants to respond to a central target flanked
      by distractors, and the feature and conjunction visual search, which requires
      participants to search for a predesignated target embedded among a variable
      number of distractors. The results showed that children with attention
      difficulties encountered major problems only when responding to a central target
      flanked by adjacent incongruent distractors and when searching for a conjunctive
      target in a high-density display. These results suggest that children with
      attention difficulties have a characteristic inability to restrict visual
      attention to a limited spatial area so as to selectively process relevant
      information while effectively ignoring distracting information.

PMID- 15493435
TI  - Consequences of comorbidity of developmental coordination disorders and learning
      disabilities for severity and pattern of perceptual-motor dysfunction.
AB  - Children with developmental coordination disorder (DCD) have difficulty learning
      and performing age-appropriate perceptual-motor skills in the absence of
      diagnosable neurological disorders. Descriptive studies have shown that
      comorbidity of DCD exists with attention-deficit/hyperactivity disorder (ADHD)
      and learning disabilities (LD). This study examined the consequences of the
      comorbidity of DCD and LD for the severity and pattern of perceptual-motor
      dysfunction. Compared to children with DCD without LD, children with comorbid DCD
      and LD performed lower on a standardized assessment of perceptual-motor ability.
      Furthermore, it appeared that children with combined DCD and LD have particular
      difficulty performing manual dexterity and balance tasks but not ball-skill
      tasks. Implications for understanding the relationship between LD and perceptual
      motor problems are discussed. We conclude that the comorbidity of DCD and LD not
      only affects the severity of perceptual-motor dysfunction but also is associated
      with a distinctive pattern of perceptual-motor dysfunction.

PMID- 15493436
TI  - Reading comprehension skills of young adults with childhood diagnoses of
      dyslexia.
AB  - This study explores the contribution of cognitive processes to comprehension
      skills in adults who suffered from childhood developmental dyslexia (CD). The
      performance of adults with CD (ages 17 to 23), chronological age-matched (CA)
      adults, and reading level-matched (RL) children was compared on measures of
      phonological processing, naming speed, working memory (WM), general knowledge,
      vocabulary, and comprehension. The results showed that adults with CD scored
      lower on measures of phonological processing, naming speed, WM, general
      knowledge, and vocabulary when compared to CA readers but were comparable to RL
      children on the majority of process measures. Phonological processing, naming
      speed, vocabulary, general knowledge, and listening comprehension contributed
      independent variance to reading comprehension accuracy, whereas WM, intelligence,
      phonological processing, and listening comprehension contributed independent
      variance to comprehension fluency. Adults with CD scored lower than CA adults and
      higher than RL children on measures of lexical processing, WM, and listening
      comprehension when word recognition and intelligence were partialed from the
      analysis. In summary, constraints in phonological processing and naming speed
      mediate only some of the influence of high-order processes on reading
      comprehension. Furthermore, adults with CD experience difficulties in WM,
      listening comprehension, and vocabulary independently of their word recognition
      problems and intellectual ability.

PMID- 15493437
TI  - Effect of attention therapy on reading comprehension.
AB  - This study quantified the influence of visual attention therapy on the reading
      comprehension of Grade 6 children with moderate reading disabilities (RD) in the
      absence of specific reading remediation. Thirty students with below-average
      reading scores were identified using standardized reading comprehension tests.
      Fifteen children were placed randomly in the experimental group and 15 in the
      control group. The Attention Battery of the Cognitive Assessment System was
      administered to all participants. The experimental group received 12 one-hour
      sessions of individually monitored, computer-based attention therapy programs;
      the control group received no therapy during their 12-week period. Each group was
      retested on attention and reading comprehension measures. In order to stimulate
      selective and sustained visual attention, the vision therapy stressed various
      aspects of arousal, activation, and vigilance. At the completion of attention
      therapy, the mean standard attention and reading comprehension scores of the
      experimental group had improved significantly. The control group, however, showed
      no significant improvement in reading comprehension scores after 12 weeks.
      Although uncertainties still exist, this investigation supports the notion that
      visual attention is malleable and that attention therapy has a significant effect
      on reading comprehension in this often neglected population.

PMID- 15493438
TI  - Evaluation of a numeracy intervention program focusing on basic numerical
      knowledge and conceptual knowledge: a pilot study.
AB  - The preliminary results of this study suggested that children with developmental
      dyscalculia benefit from a numeracy intervention program that focuses on basic
      numerical knowledge and conceptual knowledge. All children in the experimental
      group showed considerable and partly significant performance increases on all
      calculation components. Six children with developmental dyscalculia were trained
      individually and in small-group settings for a relatively short duration (one
      school semester). We argue that the positive intervention effects to a large
      extent are attributable to the explicit teaching of numerical domains that often
      have been found to be neglected in school mathematics.

PMID- 15493439
TI  - Mathematical learning difficulties and PASS cognitive processes.
AB  - This study examined the relationships between mathematical learning difficulties
      (MLD) and the planning, attention, simultaneous, successive (PASS) theory of
      cognitive processing. The Cognitive Assessment System (CAS) was used to measure
      the PASS processes for a group of 267 Dutch students with MLD who attended either
      general or special education. The results showed that students with MLD performed
      lower than their peers on all CAS scales and that the MLD group contained many
      students with cognitive weaknesses in planning or successive processing.
      Moreover, students who had specific difficulties with the acquisition of basic
      math facts, the automatization of such facts, or word-problem solving were found
      to have distinct PASS cognitive profiles. In order to investigate the
      relationships between cognitive abilities and improvement in the mastery of basic
      math facts and problem solving, 165 of the students with MLD were given a special
      multiplication intervention. It appeared that the effectiveness of this
      particular intervention did not differ across the groups of students with
      specific cognitive weaknesses.

PMID- 15493440
TI  - Measuring and improving health outcomes in Medicare: the Medicare HOS program.
AB  - The Medicare Health Outcomes Survey (HOS) (originally called the Health of
      Seniors Survey) was developed as a longitudinal performance measure to assess the
      physical functioning and mental well being of Medicare beneficiaries over time.
      The survey was implemented nationally in Medicare managed care organizations
      (MCOs) as part of Medicare HEDIS, 3.0/1998 and continues today. In 1998, a pilot
      test of the HOS in Medicare FFS was conducted; the pilot test concluded in 2001.
      This overview discusses the importance of functional status assessment, reviews
      the goals of the HOS, and explains how researchers and quality improvement
      professionals are using the data to explore functional status measurement issues,
      describe policy and programmatic implications for CMS, and identify opportunities
      to improve health care practice.

PMID- 15493441
TI  - Psychometric evaluation of the SF-36 health survey in Medicare managed care.
AB  - Data quality and scoring assumptions for the SF-36 Health Survey were evaluated
      among the elderly and disabled, using 1998 Cohort I baseline Medicare HOS data
      (n=177,714). Missing data rates were low, and scoring assumptions were met.
      Internal consistency reliability was 0.83 to 0.93 for the eight scales and 0.94
      and 0.89, respectively, for the physical (PCS) and mental (MCS) component summary
      measures. Results declined with increased risk factors (e.g., older age, more
      chronic conditions), but were well above accepted standards for all subgroups.
      These findings support using standard algorithms for scoring the SF-36 in the HOS
      and subgroup analyses of HOS data.

PMID- 15493442
TI  - Estimation of non-response bias in the Medicare FFS HOS.
AB  - We examined non-response bias in physical component summary scores (PCS) and
      mental component summary scores (MCS) in the Medicare fee-for-service (FFS)
      Health Outcomes Survey (HOS) using two alternative methods, response propensity
      weighting and imputation for non-respondents. The two approaches gave nearly
      identical estimates of non-response bias. PCS scores were 0.74 points lower and
      MCS scores 0.51 points lower after adjustment for non-response through imputation
      and 0.63 and 0.46 lower after adjustment for propensity weighting. These levels
      are small for component scores suggesting that survey non-response to the FFS HOS
      does not adversely affect estimates of average health status for this population.

PMID- 15493443
TI  - Measurement comparisons of the medical outcomes study and veterans SF-36 health
      survey.
AB  - The Medicare Health Outcomes Survey (HOS) uses the Medical Outcomes Study (MOS)
      SF-36 among beneficiaries enrolled in Medicare managed care programs, whereas the
      Department of Veterans Affairs (VA), Veterans Health Administration (VHA) has
      administered the Veterans version of the SF-36 for quality management purposes.
      The Veterans version is comparable to the MOS version for 6 of the 8 scales, but
      distinctly different in role physical (RP) and role emotional (RE) scales. The
      gains in precision for the Veterans SF-36 provide evidence for the use of this
      version in future applications for assessing patient outcomes across health care
      systems.

PMID- 15493444
TI  - Health status of dually eligible beneficiaries in managed care plans.
AB  - We conducted a descriptive study examining the health status of dually eligible
      beneficiaries using a sample from the Medicare Health Outcomes Survey (HOS), a
      measure of health status administered to enrollees in Medicare managed care
      (MMC). Overall, we found that dually eligible beneficiaries were sicker, more
      depressed, and reporting more pain than Medicare-only beneficiaries. Our results
      suggest that quality improvement initiatives that center on pain and depression
      management in the dually eligible population present important opportunities for
      collaboration between Medicare and Medicaid.

PMID- 15493445
TI  - Chronic conditions: results of the Medicare Health Outcomes Survey, 1998-2000.
AB  - This research examines the predictors of 2-year declines in physical and mental
      health for beneficiaries surveyed in the Medicare Health Outcomes Survey (HOS).
      Regression results indicate that age, arthritis of the hip/knee, sciatica, and
      pulmonary diseases, comorbidity at baseline, and increased comorbidity between
      baseline and followup were predictors of decline in physical health; however,
      these account for very small amounts of variance. The number of newly diagnosed
      chronic conditions and depression predicted decline in mental health.
      Beneficiaries deceased at followup were of lower socioeconomic status, and had
      lower physical and mental health scores than the analytic sample.

PMID- 15493446
TI  - Use of HOS data in Florida.
AB  - The Medicare Health Outcomes Survey (HOS) is a longitudinal cohort study that
      assesses physical and mental functioning of Medicare enrollees in MCPs. Realizing
      the potential of HOS data to improve health care, the Florida Medicare Quality
      Improvement Organization (QIO) analyzed HOS scores and shared them with M+COs to
      assist in evaluating the efficacy of their disease management programs. The QIO
      also discusses additional uses for HOS data such as cross-linking with a patient
      satisfaction survey and sharing with health care organizations that collaborate
      with the QIO.

PMID- 15493447
TI  - Coexisting illness and heart disease among elderly Medicare managed care
      enrollees.

PMID- 15493448
TI  - Risk adjustment of Medicare capitation payments using the CMS-HCC model.
AB  - This article describes the CMS hierarchical condition categories (HCC) model
      implemented in 2004 to adjust Medicare capitation payments to private health care
      plans for the health expenditure risk of their enrollees. We explain the model's
      principles, elements, organization, calibration, and performance. Modifications
      to reduce plan data reporting burden and adaptations for disabled,
      institutionalized, newly enrolled, and secondary payer subpopulations are
      discussed.

PMID- 15493449
TI  - National health expenditures, 2002.
AB  - National health expenditures (NHE) were $1.6 trillion in 2002, a 9.3-percent
      increase from 2001. For the fourth consecutive year health spending grew faster
      than the overall economy as measured by the GDP. Growth in U.S. health care
      spending rose for most health services in 2002, with hospital spending once again
      the primary driver

PMID- 15493450
TI  - Pharmacokinetics and metabolism of dietary flavonoids in humans.
AB  - Flavonoids are components of fruit and vegetables that may be beneficial in the
      prevention of disease such as cancer and cardiovascular diseases. Their
      beneficial effects will be dependent upon their uptake and disposition in tissues
      and cells. The metabolism and pharmacokinetics of flavonoids has been an area of
      active research in the last decade. To date, approximately 100 studies have
      reported the pharmacokinetics of individual flavonoids in healthy volunteers. The
      data indicate considerable differences among the different types of dietary
      flavonoids so that the most abundant flavonoids in the diet do not necessarily
      produce the highest concentration of flavonoids or their metabolites in vivo.
      Small intestinal absorption ranges from 0 to 60% of the dose and elimination half
      lives (T1/2) range from 2 to 28h. Absorbed flavonoids undergo extensive first
      pass Phase II metabolism in the small intestine epithelial cells and in the
      liver. Metabolites conjugated with methyl, glucuronate and sulfate groups are the
      predominant forms present in plasma. This review summarizes the key differences
      in absorption, metabolism and pharmacokinetics between the major flavonoids
      present in the diet. For each flavonoid, the specific metabolites that have been
      identified so far in vivo are indicated. These data should be considered in the
      design and interpretation of studies investigating the mechanisms and potential
      health effects of flavonoids.

PMID- 15493451
TI  - Detection of lipid peroxidation in vivo: total hydroxyoctadecadienoic acid and 7
      hydroxycholesterol as oxidative stress marker.
AB  - It is important to assess the oxidative injury in vivo accurately and
      inclusively, as the oxidative stress induced by various oxidants in a random and
      destructive fashion is considered to play an important role in the
      pathophysiology of a number of human disorders and diseases. We have developed an
      improved method for the measurement of lipid peroxidation in vivo, where total
      hydroxyoctadecadienoic acids (HODE) and 7-hydroxycholesterol (FCOH) were
      determined by GC/MS analysis from physiological samples after reduction with
      sodium borohydride and saponification by potassium hydroxide. In this method,
      both free and ester forms of hydroperoxides and ketones as well as hydroxides of
      linoleate and cholesterol are measured as HODE and FCOH, respectively. The ratio
      of stereo-isomers, (E,E)-HODE/(E,Z)-HODE, could be also measured. The plasma
      concentrations of total HODE were obtained as 76.5, 666 and 2225 nM for human,
      rat and mouse, respectively. It was found that HODE and FCOH could be measured
      satisfactorily by the present method from plasma, erythrocyte and urine of humans
      and experimental animals. It was also found that HODE in urine arose from both
      free and ester forms, while 8-iso-prostaglandin F2alpha was present primarily as
      a free acid form. As the concentrations of HODE were much higher than 8-iso
      prostaglandin F2alpha, HODE may well be used as a good oxidative marker in vivo.

PMID- 15493452
TI  - Changes of oxidative stress parameters in diabetic pregnancy.
AB  - BACKGROUND: The molecular aetiology of disturbed embryogenesis and other
      unfavourable outcomes in offspring of diabetic mothers is not fully understood.
      Experimental studies have suggested an involvement of radical oxygen species
      (ROS) in the teratological process. THE AIM OF OUR STUDY: To investigate if
      maternal diabetes in humans is capable of inducing alterations in vascular
      oxidative stress parameters and whether such changes are associated with
      disturbances in foetal development. METHODS: Seventy patients with pre
      gestational diabetes (PGDM) were chosen for the study: 29 (41.4%) belonged to
      class B according to White, 15 (21.4%) to class C, 8 (11.4%) to class D, 3 (4.3%)
      to class F, 3 to class R and 12 (17.1%) to class F/R. In 20 (28.6%) patients from
      this group an unfavourable outcome was noted. All patients were subjected to
      intensive insulin therapy. Glycaemia was estimated by daily self-monitoring, and
      diurnal glucose profiles and glycated haemoglobin (HbA1c) concentrations were
      measured monthly. Oxidative stress was evaluated as changed superoxide dismutase,
      catalase and glutathione peroxidase activities as well as of malondialdehyde
      (MDA) and peroxides concentrations in maternal erythrocytes and blood serum.
      RESULTS: Prior to conception, the mean glycaemia in the group that had a planned
      pregnancy was 6.6mmol/l and HBA1c was 9.35%. Throughout the course of pregnancy,
      these parameters were maintained at a level of 6.7 mmol/l and 7.85%,
      respectively. The activity of all antioxidative enzymes was lower before than
      during pregnancy, and so was the concentration of MDA. The MDA concentrations
      were higher in patients with elevated glycaemia and with an unfavourable outcome.
      The investigated ROS, the glycaemia level, as well as the concentration of HBA1c
      did not show any significant differences between pregnancies with and without
      vascular complications. Patients with a favourable perinatal outcome presented a
      higher activity of antioxidant enzymes, than those with unfavourable outcome,
      throughout the whole course of pregnancy. The appearance of unfavourable
      perinatal outcomes in relation to parameters of oxidative stress was assessed by
      logistic regression. Both SOD and GPX activities, as well as peroxides'
      concentration, showed significant correlations (p < 0.005) with foetal
      complications. However, after mean glucose levels in the studied group were
      included into these analyses, this relationship was only evident with SOD and GPX
      activity (p < 0.0016). CONCLUSION: Oxidative stress is one of several important
      factors contributing to unfavourable outcome of human diabetic pregnancy.

PMID- 15493453
TI  - Anti-inflammatory effects of Melaleuca alternifolia essential oil on human
      polymorphonuclear neutrophils and monocytes.
AB  - OBJECTIVE AND DESIGN: The fungicidal and bactericidal actions of the essential
      oil (EO) of Melaleuca alternifolia seem well established, but their anti
      inflammatory and anti-oxidative effects remain unclear. In this study, we
      investigated in vitro the possible role of whole M. alternifolia EO as a
      modulator of the oxidative response, i.e. reactive oxygen species (ROS)
      production, of leukocytes (monocytes and polymorphonuclear neutrophils (PMNs)) in
      humans. METHODS: Whole blood leukocytes from healthy human volunteers (n = 7),
      isolated from erythrocytes by haemolytic shock, were incubated for 30 min with M.
      alternifolia EO (0-0.1%) to determine their ROS production by flow cytometry with
      or without stimulation of cells. We compared the effects of 3 different
      stimulating agents acting differently on transductional pathways to stimulate the
      ROS production: a phorbol ester (PMA), formyl-methionyl-leucyl-phenylalanine
      (fMLP) and opsonised zymosan (OZ). RESULTS: As attested by the Kruskall-Wallis
      test, M. alternifolia EO at 0.1% directly stimulated ROS production by PMNs (x
      8.7 vs. 0% EO, p < 0.05) and increased the intracellular ROS produced by
      monocytes. Whichever the stimulating agent used (PMA, fMLP or OZ), M.
      alternifolia EO decreased the intracellular ROS production at the dilution of
      0.1% by PMNs and monocytes, more so with PMNs. CONCLUSION: M. alternifolia EO may
      be both a direct active mediator of the bactericidal action of the circulating
      leukocytes and may be efficient in protecting the organism from an excess of ROS,
      through an anti-oxidant and radical scavenging activity.

PMID- 15493454
TI  - Tempol reduces the activation of nuclear factor-kappaB in acute inflammation.
AB  - Recent studies have demonstrated that Tempol, a membrane-permeable radical
      scavenger, exerts protective effects in various models of inflammation and shock.
      Since nuclear factor-kappaB (NF-kappaB) is a transcription factor, which plays a
      pivotal role in the induction of genes involved in physiological processes as
      well as in the response to inflammation, we have investigated the effect of
      Tempol on NF-kappaB activation in a model of acute inflammation in mice.
      Injection of carrageenan into the pleural cavity of mice induced an acute
      inflammatory response characterized by fluid accumulation in the pleural cavity,
      which contained a large number of neutrophils, as well as an increased production
      of tumor necrosis factor-alpha, (TNF-alpha) and interleukin-1alpha (IL-1alpha).
      Tempol (100mg/kg i.p 30min prior to carrageenan administration) significantly
      attenuated the degree of pleuritis caused by carageeenan (all parameters
      measured). Administration of carageeenan into the chest cavity (pleuritis) was
      associated with the activation of NF-kappaB in the lung. In particular, the
      appearance of IkappaB-alpha in homogenates of lung tissue was investigated by
      immunoblot analysis at 4h after carrageenan administration. IkappaB-alpha levels
      were substantially reduced in the lung tissue from carrageenan-treated mice in
      comparison with sham-treated mice. Furthermore, to detect any effects of Tempol
      on NF-kappaB/DNA binding, lung extracts were analyzed by EMSA. The DNA binding
      activity significantly increased in extracts obtained from lungs of vehicle
      treated mice at 4h after carrageenan administration. Treatment of mice with
      Tempol caused a significant inhibition of carrageenan-induced IkappaB-alpha
      degradation and NF-kappaB/DNA binding activity. These data confirm that Tempol
      exerts potent anti-inflammatory properties and clearly demonstrates for the first
      time that Tempol reduces the activation of NF-kappaB in vivo.

PMID- 15493456
TI  - Improved FIA-ABTS method for antioxidant capacity determination in different
      biological samples.
AB  - In order to evaluate the actual antioxidant features of foods, beverages and also
      plasma from patients, a number of assays have been developed in the last few
      years to determine the so called total antioxidant activity (TAA), intended as
      the cumulative capacity of a biological sample to scavenge free radicals. Most of
      the assays partially failed in obtaining a good reproducibility when using plasma
      because it is composed of a large number of substances, some of which are present
      at very high concentrations and possess masking features. For these reasons we
      have improved the widely known ABTS method by means of a FIA system where both
      temperature and dispersion of sample and reagent were strictly controlled. We
      found that temperature may be a critical aspect in the measurement of plasma TAA
      whilst its influence may be less important in the assay of non-complex biological
      samples. We demonstrated that also the reaction time may be critical, depending
      on the nature of the substance employed. Data confirmed the high TAA of a
      methylsalicylate-containing mouthrinse as well as the negligible TAA offered by
      the chlorhexidine containing one. White wines (Verdicchio) also displayed
      interesting TAA values. The improved method was useful to screen rapidly, without
      dilution, with very limited handling of the sample and with high repeatability
      the TAA of plasma in addition to chemical products, beverages and non-complex
      biological mixtures.

PMID- 15493455
TI  - Early differential gene expression of rat lung after exposure to paraquat.
AB  - Paraquat (PQ), a quaternary nitrogen herbicide, is highly toxic to humans and
      animals. Acute poisoning and death due to PQ exposure have been reported over the
      past few decades. Excessive production of oxygen free radicals has been proposed
      to play an important role in the pulmonary pathology. The aim of the present work
      was to evaluate the implications for genes that are regulated by oxidative stress
      at the early stage of PQ exposure in rat lungs. We performed differential display
      RT-PCR (DD-PCR) on total RNA extracted from rat lungs after injection of 20mg per
      kg body weight. The experimental DD-PCR conditions, primer length and annealing
      temperature, were adjusted to improve reproducibility, and 19 differentiated
      clones were isolated. Sequence analysis followed by conventional RT-PCR and real
      time RT-PCR analyses were used to confirm the results. Four clones were finally
      determined to be significantly affected. These genes were mRNAs for plasma
      phospholipid transfer protein (PLTP), CL1BA protein, (latrophilin: LPH), and
      alphaII-spectrin as well as one unknown gene. We demonstrated the distribution of
      mRNA expression of one gene, LPH, in lung tissues. The present study suggests
      that 20mg per kg intraperitoneal PQ affects the expression of numerous genes in
      the lung at 3 h, the onset of pulmonary injury, and that the four genes specified
      may be major contributors to serious lung injury due to PQ exposure.

PMID- 15493457
TI  - Suppression of 8-oxo-2'-deoxyguanosine formation and carcinogenesis induced by N
      nitrosobis (2-oxopropyl)amine in hamsters by esculetin and esculin.
AB  - Effects of esculetin (6,7-dihydroxycoumarin) and its glycoside, esculin, on 8-oxo
      2'-deoxyguanosine (8-oxodG) formation and carcinogenesis induced by a chemical
      carcinogen, N-nitrosobis(2-oxopropyl)amine (BOP), were examined in the pancreas
      of female Syrian golden hamsters. Animals were administered esculetin by gastric
      intubation into the stomach 30 min before BOP administration or ingestion of a
      diet containing esculin for 7 days before BOP administration, and killed 1 or 4h
      after BOP treatment, and the contents of thiobarbituric acid-reacting substrates
      (TBARS) and 8-oxodG in the pancreas were determined. Both compounds suppressed
      significantly the BOP-induced increases in 8-oxodG and TBARS contents in hamster
      pancreas. We further investigated the effect of esculin on pancreatic
      carcinogenesis by the rapid production model induced by augmentation pressure
      with a choline-deficient diet, ethionine, methionine and BOP. Esculin was given
      ad libitum as a 0.05% aqueous solution in either the initiation or promotion
      phases. The incidence of invasive tumors in animals given esculin during the
      initiation phase was significantly smaller than in the control group, while
      esculin given during the promotion phase showed no apparent effects. These
      results suggest that the intake of esculin has an inhibitory effect on BOP
      induced oxidative DNA damage and carcinogenesis in hamster pancreas.

PMID- 15493458
TI  - Hypoxia-Inducible Factor in ringed seal (Phoca hispida) tissues.
AB  - Tissue hypoxia and ischemia-reperfusion pose a dangerous situation for oxidative
      stress. However, diving mammals and birds show pronounced resistance to oxidative
      injury under such conditions, which are a consequence of selective
      vasoconstriction during a dive. As the function of Hypoxia-Inducible Factor
      1alpha (HIF-1alpha) in protection against and adaptation to hypoxia has been
      recognized in terrestrial animals, we have investigated the genomics and
      expression of this protein in ringed seal (Phoca hispida) in order to determine
      if it may play a protective role in this diving mammal. PCR studies using primers
      based on sequences from mouse HIF-1alpha exons 3, 4, 5, 6, 9, 10, 11, 12 and 15
      showed that DNA from seal lung generated PCR products similar to those from mouse
      DNA. These studies have established that a putative HIF-1alpha gene exists in the
      seal genome that appears to have a similar but not identical sequence to the
      mouse gene. Seal lung and skeletal muscle tissues showed the highest relative
      levels of HIF-1alpha protein expression, with heart muscle showing significantly
      lower levels, and levels of HIF-1beta protein expression paralleled this
      situation. Analysis of oxidized cellular protein levels indicated that seal lung
      and heart muscle had the lowest levels of oxidized proteins. Thus, as seal lung
      tissue had the highest level of HIF-1alpha protein expression and the second
      lowest level of protein oxidation, this suggests that HIF-1alpha expression may
      have an important protective effect in this tissue in diving mammals. Our results
      support the hypothesis that HIF-1alpha expression is dependent on both tissue
      specific energy requirements and adequate metabolic supply-to-demand ratio.
      Combined, the evidence available suggests that diving mammals have an overall
      anticipatory response to avoid the ill effects of dive-associated ischemia
      reperfusion which may involve the HIF-1 system.

PMID- 15493459
TI  - Oxidative decomposition of vitamin C in drinking water.
AB  - We have previously shown that vitamin C (ascorbic acid) can initiate hydroxyl
      radical formation in copper contaminated household drinking water. In the present
      study, we have examined the stability of vitamin C in copper and bicarbonate
      containing household drinking water. In drinking water samples, contaminated with
      copper from the pipes and buffered with bicarbonate, 35% of the added vitamin C
      was oxidized to dehydroascorbic acid within 15 min. After 3h incubation at room
      temperature, 93% of the added (2 mM) ascorbic acid had been oxidized. The
      dehydroascorbic acid formed was further decomposed to oxalic acid and threonic
      acid by the hydrogen peroxide generated from the copper (I) autooxidation in the
      presence of oxygen. A very modest oxidation of vitamin C occurred in Milli-Q
      water and in household water samples not contaminated by copper ions. Moreover,
      addition of vitamin C to commercially sold domestic bottled water samples did not
      result in vitamin C oxidation. Our results demonstrate that ascorbic acid is
      rapidly oxidized to dehydroascorbic acid and further decomposed to oxalic- and
      threonic acid in copper contaminated household tap water that is buffered with
      bicarbonate. The impact of consuming ascorbic acid together with copper and
      bicarbonate containing drinking water on human health is discussed.

PMID- 15493460
TI  - Cigarette smokers have decreased lymphocyte and platelet alpha-tocopherol levels
      and increased excretion of the gamma-tocopherol metabolite gamma-carboxyethyl
      hydroxychroman (gamma-CEHC).
AB  - Cigarette smoking is associated with increased oxidative stress and increased
      risk of degenerative disease. As the major lipophilic antioxidant, requirements
      for vitamin E may be higher in smokers due to increased utilisation. In this
      observational study we have compared vitamin E status in smokers and non-smokers
      using a holistic approach by measuring plasma, erythrocyte, lymphocyte and
      platelet alpha- and gamma-tocopherol, as well as the specific urinary vitamin E
      metabolites alpha- and gamma-carboxyethyl-hydroxychroman (CEHC). Fifteen smokers
      (average age 27 years, smoking time 7.5 years) and non-smokers of comparable age,
      gender and body mass index (BMI) were recruited. Subjects completed a 7-day food
      diary and on the final day they provided a 24 h urine collection and a 20 ml
      blood sample for measurement of urinary vitamin E metabolites and total vitamin E
      in blood components, respectively. No significant differences were found between
      plasma and erythrocyte alpha- and gamma-tocopherol in smokers and non-smokers.
      However, smokers had significantly lower alpha-tocopherol (mean+/-SD, 1.34+/-0.31
      micromol/g protein compared with 1.94+/-0.54, P = 0.001) and gamma-tocopherol
      (0.19+/-0.04 micromol/g protein compared with 0.26+/-0.08, P = 0.026) levels in
      their lymphocytes, as well as significantly lower alpha-tocopherol levels in
      platelets (1.09+/-0.49 micromol/g protein compared with 1.60+/-0.55, P = 0.014;
      gamma-tocopherol levels were similar). Interestingly smokers also had
      significantly higher excretion of the urinary gamma-tocopherol metabolite, gamma
      CEHC (0.49+/-0.25mg/g creatinine compared with 0.32+/-0.16, P = 0.036) compared
      to non-smokers, while their alpha-CEHC (metabolite of alpha-tocopherol) levels
      were similar. There was no significant difference between plasma ascorbate, urate
      and F2-isoprostane levels. Therefore in this population of cigarette smokers
      (mean age 27 years, mean smoking duration 7.5 years), alterations to vitamin E
      status can be observed even without the more characteristic changes to ascorbate
      and F2-isoprostanes. We suggest that the measurement of lymphocyte and platelet
      vitamin E may represent a valuable biomarker of vitamin E status in relation to
      oxidative stress conditions.

PMID- 15493461
TI  - The inhibitory effect of luteolin-7-O-glucoside on the formation of pentyl and 7
      carboxyheptyl radicals from 13-hydroperoxy-9,11-octadecadienoic acid in the
      presence of iron(II) ions.
AB  - A flavone glucoside, luteolin-7-O-glucoside (luteolin-7-G) inhibited the
      formation of pentyl and 7-carboxyheptyl radicals in the reaction of 13
      hydroperoxy-9,11-octadecadienoic (13-HPODE) acid with iron(II) ions. The
      inhibitory effect of luteolin-7-G was diminished in the presence of EDTA. These
      results indicated that the inhibitory effects of luteolin-7-G occur partly
      through the chelation of iron ions. Measurement of visible spectra also showed
      that luteolin-7-G chelates iron ions. On the other hand, luteolin-7-G did not
      inhibit the reaction under anaerobic conditions, suggesting that oxygen molecules
      participate in the inhibition. Oxygen consumption measurements showed that the
      luteolin-7-G/iron ion complexes react with oxygen molecules in competition with
      13-HPODE acid, and free iron ions exclusively react with 13-HPODE acid. The
      reaction of luteolin-7-G/iron ion complexes with oxygen molecules possibly
      diminishes the formation of pentyl and 7-carboxyheptyl radicals.

PMID- 15493462
TI  - Properties of quercetin conjugates: modulation of LDL oxidation and binding to
      human serum albumin.
AB  - Quercetin is an important dietary flavonoid with in vitro antioxidant activity.
      However, it is found in human plasma as conjugates with glucuronic acid, sulfate
      or methyl groups, with no significant amounts of free quercetin present. The
      antioxidant properties of the conjugates found in vivo and their binding to serum
      albumin are unknown, but essential for understanding possible actions of
      quercetin in vivo. We, therefore, tested the most abundant human plasma quercetin
      conjugates, quercetin-3-glucuronide, quercetin-3'-sulfate and isorhamnetin-3
      glucuronide, for their ability to inhibit Cu(II)-induced oxidation of human low
      density lipoprotein and to bind to human albumin, in comparison to free
      flavonoids and other quercetin conjugates. LDL oxidation lag time was increased
      by up to four times by low (<2 microM) concentrations of quercetin-3-glucuronide,
      but was unaffected by equivalent concentrations of quercetin-3'-sulfate and
      isorhamnetin-3-glucuronide. In general, the compounds under study prolonged the
      lag time of copper-induced LDL oxidation in the order: quercetin-7-glucuronide >
      quercetin > quercetin-3-glucuronide = quercetin-3-glucoside > catechin >
      quercetin-4'-glucuronide > isorhamnetin-3-glucuronide > quercetin-3'-sulfate.
      Thus the proposed products of small intestine metabolism (quercetin-7
      glucuronide, quercetin-3-glucuronide) are more efficient antioxidants than
      subsequent liver metabolites (isorhamnetin-3-glucuronide, quercetin-3'-sulfate).
      Albumin-bound conjugates retained their property of protecting LDL from
      oxidation, although the order of efficacy was altered (quercetin-3'-sulfate >
      quercetin-7-glucuronide > quercetin-3-glucuronide > quercetin-4'-glucuronide =
      isorahmnetin-3-glucuronide). Kq values (concentration required to achieve 50%
      quenching) for albumin binding, as assessed by fluorescence quenching of Trp214,
      were as follows: quercetin-3'-sulfate (approximately 4 microM)= quercetin > or =
      quercetin-7-glucuronide > quercetin-3-glucuronide = quercetin-3-glucoside >
      isorhamnetin-3-glucuronide > quercetin-4'-glucuronide (approximately 20 microM).
      The data show that flavonoid intestinal and hepatic metabolism have profound
      effects on ability to inhibit LDL oxidation and a lesser but significant effect
      on binding to serum albumin.

PMID- 15493463
TI  - Mathematics and learning disabilities.
AB  - Between 5% and 8% of school-age children have some form of memory or cognitive
      deficit that interferes with their ability to learn concepts or procedures in one
      or more mathematical domains. A review of the arithmetical competencies of these
      children is provided, along with discussion of underlying memory and cognitive
      deficits and potential neural correlates. The deficits are discussed in terms of
      three subtypes of mathematics learning disability and in terms of a more general
      framework for linking research in mathematical cognition to research in learning
      disabilities.

PMID- 15493464
TI  - Mathematics education in the United States: past to present.
AB  - This article presents a historical review of mathematics education since the late
      1950s in the United States. Three themes are used to organize the literature
      reviewed in the article: (a) broad sociopolitical forces, particularly highly
      publicized educational policy statements; (b) trends in mathematics research; and
      (c) theories of learning and instruction. At times, these themes coincide, as was
      the case in the 1990s. In other cases, such as the recent push for educational
      accountability, these themes conflict. Nonetheless, the themes go a long way to
      explain the serpentine nature of reform in the United States over the last 45
      years. This article also attempts to account for developments in special
      education as well as general education research, something that does not appear
      in most historical presentations of mathematics education.

PMID- 15493465
TI  - Learning difficulties in numeracy in Australia.
AB  - In this article, we provide an understanding of the term numeracy as it is used
      in Australia and a description of numeracy education in this country. In
      particular, we discuss the role of outcomes-based curriculum frameworks and
      outline the dominant teaching approaches. The focus is on students with learning
      difficulties and how they are identified and supported in schools. We create two
      vignettes based on real students with difficulties in numeracy, which highlight
      two of the most common problems. We report on the prevalence of learning
      difficulties in numeracy in Australia and describe some of the initiatives
      related to the assessment and enhancement of learning in numeracy that are being
      undertaken in various states in Australia. Finally, we identify some of the
      future challenges facing the Australian education system in this area. These
      challenges relate to teacher knowledge, mandated assessment, and the role of
      parents. We conclude the article by calling for the evaluation of current
      assessment and intervention initiatives as well as the development of a national
      program to support the goal of numeracy for all students.

PMID- 15493466
TI  - Arithmetic education and learning disabilities in Italy.
AB  - In the first part of this article, we briefly present the context of mathematics
      education in Italy and its specific programs, teaching and assessment methods,
      use of psychological concepts, and policies in favor of pupils with difficulties.
      We illustrate the importance and the role of mathematics teachers' associations.
      In the second part, we focus more directly on the issue of arithmetic learning
      and learning disabilities in Italy. Despite the absence of a specific strong
      tradition in the field, new perspectives regarding mathematics education are
      evident in Italy. The preparation of new assessment tools has proceeded together
      with an effort toward the identification of subtypes of arithmetic learning
      disabilities. A basic distinction has been made between difficulties in number
      processing/calculation and problem-solving tasks. Within the area of calculation,
      a finer distinction between numerical knowledge, speed, and accuracy seems
      critical, but a more articulated differentiation of subcomponents relying on
      modern cognitive-neuropsychological models can be used also.

PMID- 15493467
TI  - Children with mathematics learning disabilities in Belgium.
AB  - In Belgium, between 3% and 8% of the children in elementary schools have
      mathematics learning disabilities (MLD). Many of these children have less
      developed linguistic, procedural, and mental representation skills. Moreover, a
      majority of the children have been found to show inaccurate prediction and
      evaluation skills in Grade 3. MLD often become obvious in elementary school.
      Whereas some children are retained, others are referred to special education.
      During the last 10 years, the number of children in special education and the
      number of children with learning disabilities who are following a special
      guidance program in general education (inclusive education) have increased.
      Children in Belgium with MLD can get therapy for about 2 years. Nevertheless,
      many problems continue unresolved even in high school and adulthood.

PMID- 15493468
TI  - Mathematics education and learning disabilities in Spain.
AB  - In the first part of this article, we describe the basic objectives of the math
      curriculum in Spain as well as the basic contents, teacher resources, and
      obstacles perceived in mathematics instruction. Second, we briefly describe the
      concept of learning disabilities (LD) as they are currently defined in Spain. As
      stated in the recent educational reform, a student with LD is any student with
      special educational needs. The emphasis is placed on the educational resources
      that these students need in order to achieve the curricular objectives that
      correspond to their age group or grade. Third, we comment specifically on the
      educational services model and the evaluation and instructional procedures for
      students with math learning disabilities. Finally, we describe some lines of
      research that have appeared in the last few years in Spain that have led to the
      development of new evaluation and intervention procedures for students with LD in
      computation and problem solving.

PMID- 15493469
TI  - Mathematics and academic diversity in Japan.
AB  - Japanese education has been the subject of considerable research and educational
      commentary in the United States over the last 20 years. Since the early 1990s,
      there has been increased interest in Japanese methods for teaching mathematics,
      and the Third International Mathematics and Science Study has accelerated
      American interest in Japanese methods. Observational studies, teacher and student
      surveys, and analyses of classroom videotapes have provided a rich picture of how
      the Japanese teach the whole class. However, little has been written about how
      academically low-achieving math students fare in Japanese schools. This article
      briefly summarizes Japanese methods for teaching mathematics and describes how
      the educational system addresses academic diversity. It concludes with a
      description of a method for teaching mathematics that some Japanese mathematics
      educators feel has promise for students with learning disabilities.

PMID- 15493470
TI  - Endometrium implantation and ectopic pregnancy.
AB  - Embryo in uterine implantation is a complex and multifactor-related process and
      is a downstream and ideal point for woman fertility control. Understanding the
      cellular and molecular mechanism of implantation is a prerequisite for
      development of anti-implantation contraceptives. In spite of considerable
      accumulation of information from the laboratory animals that has been achieved,
      it is difficult to generate such information in human due to ethical restriction
      and experimental limitation, and the present knowledge for understanding the
      definitive mechanisms which control these events remains elusive. Embryo
      implantation can also occur outside uterus. Some women with abdominal pregnancies
      could successfully complete the processes of gestation and bear normal babies,
      implying that implantation itself may be not an endometrium-specific process.
      Reproductive biologists should cooperate with gynecologists to further
      comparatively study the molecular and cellular mechanisms of implantation
      normally occurring in endometrium and abnormally appearing outside uterine
      cavity. Such collaborative studies may generate new important information for
      developing anti-implantation contraceptive and for techniques of accurate
      diagnosis of ectopic pregnancy. A specially designed GnRH-2 analog and a
      combination use of low dose RU486 and gossypol as anti-implantation
      contraceptives have been suggested.

PMID- 15493471
TI  - Mitogen-activated protein kinases mediate the oxidative burst and saponin
      synthesis induced by chitosan in cell cultures of Panax ginseng.
AB  - Chitosan (CHN) specially induced the activities of 39 kD and 42 kD protein
      kinases in ginseng cells, which could be suppressed by an inhibitor of mitogen
      activated protein kinase (MAPK) pathway, PD98059. The immunoprecipitation (IP)
      using MAPK antibody or kinase assay in vitro also showed that CHN-induced 42 kD
      and 39 kD protein kinases belonged to the MAPK family. PD98059 suppressed CHN
      induced transcriptions of ginseng squalene synthase and ginseng squalene
      epoxidase genes (gss and gse), CHN-induced accumulation of beta-Amyrin synthase
      (beta-AS) and synthesis of saponin. These results showed that CHN-induced
      activities of MAPKs were necessary for the CHN-induced saponin synthesis. EGTA
      and LaCl3 suppressed CHN-induced 39 kD and 42 kD MAPK activities. Ruthenium red
      (RR) could suppress CHN-induced 39 kD activity. All of them suppressed CHN
      induced saponin synthesis. These results indicated that CHN-induced increment of
      cytosolic calcium was necessary for CHN-induced saponin synthesis. PD98059 also
      suppressed CHN-induced oxidative burst (including the increment of activity of
      plasma membrane NADPH oxidase and production of H2O2), but diphenylene iodonium
      (DPI), dimethylthiourea (DMTU) and 2,5-dihydroxycinnamic acid methyl ester (DHC)
      could not suppress CHN-induced MAPK activities, which indicated that MAPK was
      possibly function upstream of CHN-induced oxidative burst.

PMID- 15493472
TI  - Prokaryote phylogeny based on ribosomal proteins and aminoacyl tRNA synthetases
      by using the compositional distance approach.
AB  - In order to show that the newly developed K-string composition distance method,
      based on counting oligopeptide frequencies, for inferring phylogenetic relations
      of prokaryotes works equally well without requiring the whole proteome data, we
      used all ribosomal proteins and the set of aminoacyl tRNA synthetases for each
      species. The latter group has been known to yield inconsistent trees if used
      individually. Our trees are obtained without making any sequence alignment.
      Altogether 16 Archaea, 105 Bacteria and 2 Eucarya are represented on the tree.
      Most of the lower branchings agree well with the latest, 2003, Outline of the
      second edition of the Bergey's Manual of Systematic Bacteriology and the trees
      also suggest some relationships among higher taxa.

PMID- 15493473
TI  - Distribution of T-DNA carrying a Ds element on rice chromosomes.
AB  - Over 3000 rice plants with T-DNA carrying a Ds element were constructed by
      Agrobacterium tumefaciens mediation. Using inverse PCR methodology, 590 unique
      right flanking sequences of T-DNA (Ds) were retrieved from independent
      transformants and classified into six main types on the basis of the origin of
      filler DNA between the right border of T-DNA and flanking sequence of rice
      genome. Type I sequences were the most common and showed canonical integration
      that T-DNA right border was followed by rice genome sequence with or without
      filler DNA of no more than 50 bp, while type II sequences displayed a vector
      genome combination that T-DNA right border was followed by a vector fragment and
      then connected with rice genome sequence. The location and distribution of 340
      type I and II flanking sequences on the rice chromosome were determined using
      BLAST analysis. The 340 Ds insertions at an average interval of 0.8 megabase (Mb)
      constructed a basic framework of Ds starter points on whole rice chromosomes. The
      frequency of T-DNA (Ds) inserted into the exons of predicted genes on chromosome
      one was 21%. Knowledge of T-DNA (Ds) locations on chromosomes will prove to be a
      useful resource for isolating rice genes by Ds transposon tagging as these Ds
      insertions can be used as starting lines for further mutagenesis.

PMID- 15493474
TI  - Quantitative analyses of relationships between ecotoxicological effects and
      combined pollution.
AB  - The responses of wheat Triticum aestivum, rice Oryza sativa, earthworms Eisenia
      foetida, and prawns Penaeus japonicus to combined acetochlor-Cu, Cd-Zn were
      studied in hydroponic and soil-culturing systems using the methods of
      ecotoxicology. In particular, systematically quantitative analyses were
      documented by field experiments. Results showed that ecotoxicological effects
      under the combined pollution were not only related to chemical properties of
      pollutants but also dependent on the concentration level of pollutants, in
      particular on the combination of concentrations of pollutants in ecosystems.
      Additionally, species of organisms, especially the type of ecosystem, determined
      the influences. To some extent, biological tissue targets attacked by pollutants
      were an important factor.

PMID- 15493475
TI  - Effects of dragon's blood resin and its component loureirin B on tetrodotoxin
      sensitive voltage-gated sodium currents in rat dorsal root ganglion neurons.
AB  - Using whole-cell patch clamp technique on the membrane of freshly isolated dorsal
      root ganglion (DRG) neurons, the effects of dragon's blood resin and its
      important component loureirin B on tetrodotoxin-sensitive (TTX-S) voltage-gated
      sodium currents were observed. The results show that both blood resin and
      loureirin B could suppress TTX-S voltage-gated sodium currents in a dose
      dependent way. The peak current amplitudes and the steady-state activation and
      inactivation curves are also made to shift by 0.05% blood resin and 0.2 mmol/L
      loureirin B. These results demonstrate that the effects of blood resin on TTX-S
      sodium current may contribute to loureirin B in blood resin. Perhaps the
      analgesic effect of blood resin is caused partly by loureirin B directly
      interfering with the nociceptive transmission of primary sensory neurons.

PMID- 15493476
TI  - Cloning and expression analysis in mature individuals of two chicken type-II GnRH
      (cGnRH-II) genes in common carp (Cyprinus carpio).
AB  - Gonadotropin-releasing hormone (GnRH) is a conservative neurodecapeptide family,
      which plays a crucial role in regulating the gonad development and in controlling
      the final sexual maturation in vertebrate. Two differing cGnRH-II cDNAs of common
      carp, namely cGnRH-II cDNA1 and cDNA2, were firstly cloned from the brain by
      rapid amplification of cDNA end (RACE) and reverse transcription- polymerase
      chain reaction (RT-PCR). The length of cGnRH-II cDNA1 and cDNA2 was 622 and 578
      base pairs (bp), respectively. The cGnRH-II precursors encoded by two cDNAs
      consisted of 86 amino acids, including a signal peptide, cGnRH-II decapeptide and
      a GnRH-associated peptide (GAP) linked by a Gly-Lys-Arg proteolytic site. The
      results of intron trapping and Southern blot showed that two differing cGnRH-II
      genes in common carp genome were further identified, and that two genes might
      exist as a single copy. The multi-gene coding of common carp cGnRH-II gene
      offered novel evidence for gene duplication hypothesis. Using semi-quantitative
      RT-PCR, expression and relative expression levels of cGnRH-II genes were detected
      in five dissected brain regions, pituitary and gonad of common carp. With the
      exception of no mRNA2 in ovary, two cGnRH-II genes could be expressed in all the
      detected tissues. However, expression levels showed an apparent difference in
      different brain regions, pituitary and gonad. According to the expression
      characterization of cGnRH-II genes in brain areas, it was presumed that cGnRH-II
      might mainly work as the neurotransmitter and neuromodulator and also operate in
      the regulation for the GnRH releasing. Then, the expression of cGnRH-II genes in
      pituitary and gonad suggested that cGnRH-II might act as the autocrine or
      paracrine regulator.

PMID- 15493477
TI  - Homology modeling three-dimensional structure of AnxB1 and reducing its
      immunogenicity by sequence-deleted mutagenesis.
AB  - AnxB1, a novel annexin previously isolated from Cysticercus cellulose, shows high
      thrombi affinity and anticoagulant activity in vivo. In order to investigate the
      relationship between structure and biological function, a predicted three
      dimensional (3D) model of AnxB1 was generated by homology modeling. This model
      contains four homologous internal-domains and the Ca trace of domain I, II and IV
      shows high similarity. Based on the structure characterization, four sequence
      deleted mutants were constructed and expressed as GST fusion proteins in E. coli.
      Two of the mutants, GST-M3 and GST-M4 reserved high anticoagulant activity
      (p<0.01 vs. GST). Furthermore, compared with the wild type GST-AnxB1, the
      immunogenicity of GST-M3 and GST-M4 was reduced significantly (p<0.01) and the
      molecular weight was lowered to 27 kD and 34 kD, respectively. These observations
      laid a solid foundation for further study on developing new thrombolytic agents
      with higher efficiency and lower side effect.

PMID- 15493478
TI  - Effective suppression of fibronectin synthesis by retrovirus delivered shRNA in
      rat cardiac fibroblasts.
AB  - Extracellular matrix overexpression is a common final pathway that leads to
      ventricular remodeling. Fibronectin plays a pivotal role in this progress. In the
      work presented here, we explored the possibility of direct inhibition of
      fibronectin synthesis in rat cardiac fibroblasts by small interference RNA
      (siRNA). We found that siRNA could successfully suppress the fibronectin
      overexpression stimulated by angiotensin II. To overcome the limitations of
      plasmid-based siRNA, we subcloned the H1 promoter into pLXIN, a commercially
      available retroviral vector. We found that H1 promoter worked very well to form
      the small hairpin RNA (shRNA) on the retroviral vector, and the fibronectin
      expression was dramatically down regulated by shRNA. We think the retroviral
      shRNA delivery system that we have constructed may have potential roles in
      treating ventricular remodeling.

PMID- 15493479
TI  - Chromatography studies on bio-affinity of nine ligands of alpha1-adrenoceptor to
      alpha1D subtypes overexpressed in cell membrane.
AB  - To improve selectivity and specificity of cell membrane chromatography (CMC), the
      chromatography affinities of nine ligands of alpha1-adrenergic receptor(AR)to
      alpha1D-AR subtype were investigated. The human embryonic kidney (HEK) 293 cells
      expressed by cDNA of alpha1D-AR subtypes were cultured and cell membrane
      stationary phase (CMSP) was prepared. Then the interactions between ligands and
      alpha1D-AR in CMSP were investigated using CMC. The affinity rank order to
      alpha1D-AR subtype obtained from CMC for the nine alpha1-adrenoceceptor ligands
      is: prazosin, BMY7378, phentolamine, oxymetazoline, 5-methylurapidil,
      norepinephrine, phenylephrine, methoxamine, RS-17053. The affinity rank order is
      similar and correlates well with that obtained from others' radioligand binding
      assays (RBA). CMSP prepared by transfected HEK293 cells with alpha1-D
      adrenoceptor cDNA and CMC method could be used to evaluate affinities of -drug
      receptor and drug-receptor subtypes and to screen drugs selective to alpha1D-AR.

PMID- 15493480
TI  - Effect of cDNA fragments in different length derived from potato virus Y coat
      protein gene on the induction of RNA-mediated virus resistance.
AB  - We have reported that cDNA derived from entire coat protein (CP) gene of potato
      virus Y (PVY) could induce resistance to PVY infection in transgenic tobacco
      plants, and the resistance was further demonstrated to be RNA-mediated rather
      than coat protein-mediated. In this study, we cloned cDNA fragments of 202 bp,
      417 bp, and 603 bp in length derived from the 3' end of the PVY CP gene, and the
      cDNA fragments were introduced into tobacco (var. NC89) plants via Agrobacterium
      mediated transformation system. The results of resistance assay showed that the
      CP cDNA fragments of 417 bp and 603 bp could confer resistance of the transgenic
      plants to PVY infection, but the fragment of 202 bp in length could not.
      Molecular analysis revealed that the resistance was RNA-mediated, which is
      believed to be a result of post-transcriptional gene silencing. The results
      indicate that the length of cDNA fragments needed for resistance induction was
      located somewhere between 202 bp and 417 bp from the 3' end of PVY CP gene.

PMID- 15493481
TI  - [Self esteem and lack of self esteem].

PMID- 15493482
TI  - [Listening, understanding, explaining].

PMID- 15493483
TI  - [Cranial-cerebral trauma after a traffic accident: perceptions of patients,
      family, physicians and professionals].
AB  - This is a study of medical care when road accident incidents result in traumatic
      brain injury (TBI). We investigated the personal perceptions of those involved in
      acute care episodes and subsequent rehabilitation. We conducted simultaneous semi
      structured interviews with individuals who had sustained a TBI (8) and their
      families (8). We then conducted semi-structured individual interviews with the
      professionals (22) and physicians (9) who attended them. Results reveal the
      difficulties encountered by the different people involved, from the standpoint of
      the rehabilitation of both the person who with the TBI and their families, the
      relationships among the various actors, and the continuity of care. The results
      disclose the importance of including the family and the TBI casualty in the care
      process by endorsing their participation and by setting up suitable structures
      that prioritize a meaningful partnership among the individuals, families,
      physicians, professionals and health care organizations and in which each person
      can play a role as an agent in the care of the person with the TBI. An important
      element, which came out again in our results, is that the shortage of information
      provided to the families can jeopardize establishing a relationship of trust
      among the actors. Furthermore, many of the family members were upset that the
      health intervention was entirely focussed on the TBI casualty: none of the
      professionals were concerned with what the families were going through, either
      during the acute care or rehabilitation. Another major problem is lack of
      communication, not just amongst the professionals, but also between institutions
      which seem to function in isolation. Lack of resources, the limited availability
      of those that are offered, and social policies are also detrimental to the
      reintegration of the TBI individual into the community. Finally, many of the
      professionals reported that they had not been trained to assist families in this
      situation.

PMID- 15493484
TI  - [Comparative study of anxiety in informed and non-informed patients in the
      preoperative period].
AB  - Operation anxiety constitutes a significant phenomenon, detectable in numerous
      sleep related and psychological symptoms, as in its impact on the patient's
      health, the operation and post-operation process. For decades this problem
      (almost unknown in Lebanese scientific research), was the object of a vast
      theoretical project and numerous North American and European studies. Within the
      framework of this investigation, we studied the influence of structured
      information, provided by operating room nurses, on the patient's anxiety during
      the preparatory stage. The problem is all the more significant and relevant given
      that it is all but ignored in Lebanese hospitals. By adopting the basic
      hypothesis that "structured preparatory information diminishes the patient's
      anxiety" we wanted to examine the eventual links between the patient's anxiety
      level and his/her personal, socio-cultural and psycho-medical characteristics
      (sex, age, marital status, education, standard of living, medical history, type
      of surgery, type of anesthesia, etc.). Using the same methodological approach, we
      adopted Spielberger's steps in measuring anxiety after having acquired the proper
      authorization from Professor Spielberger himself, who furnished us with the
      certified Arabic version of these steps and their interpretation. A questionnaire
      allowed the identification of test groups' characteristics. We chose our setting
      the operating theatre at the Nini hospital in Tripoli, North Lebanon. Our
      investigation essentially began in September/October 2003. We formulated a sample
      of sixty patients within the operating community by means of a random sampling
      technique and a well-defined exclusion criteria. With the same technique we
      divided two groups of thirty patients: group A1 which was informed and A2 which
      was uninformed and used as test subjects. The data gathered by the investigation
      was incorporated into the SPSS software. The results of the comparative analysis
      operating between the two groups' anxiety scores confirmed the afore-mentioned
      hypothesis. However, these results did not establish any significant links
      between anxiety levels and the majority of the test groups' characteristics. By
      confirming the hypothesis that preparatory information reduces the patient's
      anxiety, this investigation has opened the door to important practical
      consequences leading to the following recommmendation: quality health-care in
      Lebanese hospitals would greatly improve by adopting a protocol of information
      booklets and preparatory meetings with the patient, with the added benefit of
      valorizing the role of the operating room nurse. At present, the absence of any
      structured preparatory information represents a significant deficiency in
      Lebanese hospitals.

PMID- 15493485
TI  - [A polysemic concept: autonomy (in the case of nurses)].

PMID- 15493486
TI  - [University nursing education and its consequences on the professor's indentity].
AB  - The modification of the statute and expansion of nursing training will also lead
      to a modification of the instructor's workload. Despite previous university
      training, the new research and service provider requirements (issued by the Law
      regarding Advanced and Specialized Schools), will confront the instructor with
      new activities that he/she may have little or no experience in performing. The
      instructor's work, and his/her conflict with the assigned work, would allow an
      observation of his/her teaching practices as well as any instability brought on
      by change of status in nursing training. The instructor would now have a new
      identity: that of researcher and promoter of professional knowledge. However,
      this transformation involves the creation of a site regrouping the ensemble of
      participants where the experimental and the practical can coexist and develop.

PMID- 15493487
TI  - Kid power.

PMID- 15493488
TI  - Health out of the closet.

PMID- 15493489
TI  - Healthier chips ahoy!

PMID- 15493490
TI  - Seclusion & restraint: Where have we been? Where are we now? Where are we going?

PMID- 15493491
TI  - Kevin Ann Huckshorn, RN, MSN, CAP, ICADC.

PMID- 15493492
TI  - Changing embedded practice: lessons from gerontology.

PMID- 15493493
TI  - Reducing seclusion restraint in mental health use settings: core strategies for
      prevention.
AB  - 1. The use of seclusion and restraint (S/R) is traumatizing to consumers and
      staff, interrupts the therapeutic process, and is not conducive to recovery. 2.
      Six effective strategies to reduce S/R use have been identified and are low cost,
      easily replicable, and publicly available. 3. Organizations that wish to reduce
      S/R use need to embrace a prevention approach, follow the tenets of continuous
      quality improvement, and develop a reduction plan individualized for that
      facility. 4. Highly visible, consistent, and effective organizational leadership
      appears to be the most significant and critical component in any successful S/R
      reduction initiative.

PMID- 15493494
TI  - Sensory approaches in inpatient psychiatric settings: innovative alternatives to
      seclusion & restraint.
AB  - The national initiative to decrease the use of seclusion and restraint in
      psychiatric inpatient settings requires innovative methods to facilitate the
      processes of consumer self-organization, self-care, and positive change. Sensory
      based approaches and multisensory rooms are valuable resources as cultures of
      care shift to become more responsive and collaborative. This article explores the
      importance and efficacy of trauma-informed approaches that are sensory
      supportive, address the individual needs of the person, and strengthen the
      therapeutic relationship.

PMID- 15493495
TI  - Redefining consumer roles: changing culture & practice in mental health care
      settings.
AB  - The creation of positions for CSPs is a phenomenon with a promising future for
      the delivery of mental health services. People who have direct experiences are
      the ones who best know the possibility of recovery from mental illness. They are
      the only ones who can serve as role models for others, providing them with hope
      and inspiration. With courage and determination, CSPs will make good partners
      with non-consumer providers, each needing to listen and learn from the other to
      work together effectively and to keep the wishes of those they serve as their
      highest priority.

PMID- 15493496
TI  - [Occupational exposure to hand-transmitted vibration in Poland].
AB  - BACKGROUND: Occupational exposure to hand transmitted vibration may cause
      disorders in upper extremities known as hand-arm vibration syndrome. Therefore it
      is essential to know the sources of vibration, occupational groups exposed to
      vibration and the number of exposed workers. The aim of the study was to estimate
      the number of men and women exposed to hand-transmitted vibration in Poland.
      MATERIALS AND METHODS: The completed questionnaires were obtained from 265 (80%)
      sanitary inspection stations. They included questions on: the name of workplaces,
      the name and the type of vibration sources, workers' gender, the number of
      workers exposed to vibration, indicating the extent of exposure measured against
      the three threshold limit values (< 0.5 TLV; 0.5 < TLV < 1 and > 1 TLV), and the
      number of workers exposed to hand-transmitted vibration not documented by
      measurements in a particular workplaces, indicating one of the three possible
      kinds of exposure (occasional, periodical and constant). The questionnaire data
      were based on measurements and analyses performed in 1997-2000. RESULTS AND
      CONCLUSIONS: The results of the study showed that vibrating tools used by
      grinders, fitters, locksmiths, rammers, road workers, carpenters and smiths
      proved to be the most frequent sources of hand-transmitted vibration. It was
      revealed that 78.6% of operators of these tools were exposed to vibration
      exceeding 1 TLV. The study also indicated that 17,000 workers, including 1700
      women, were exposed to vibration exceeding the threshold limit values.

PMID- 15493497
TI  - [Health promotion activities of occupational medicine physicians at the
      workplace].
AB  - BACKGROUND: The authors address the issue of workplace health promotion (WHP)
      activities among occupational medicine physicians in Poland. In the analysis
      performed the provisions of the Occupational Health Services Act as well as the
      conclusions inferred from the most recent WHP survey were taken into account.
      MATERIALS AND METHODS: The data presented in this paper result from the 2002
      survey carried out by the National Centre for Workplace Health Promotion on a
      random sample of 325 occupational medicine physicians. RESULTS: The survey
      revealed that occupational medicine physicians mostly prefer individual-oriented
      activities such as health education of individual patients during medical
      examinations (86%), typically medical interventions like vaccinations (71%), or
      comprehensive medical checkups (53%). A modern concept of the WHP-related
      activities is not so popular. For example, health education for large groups of
      employees is undertaken by 16% of physicians, comprehensive health-related
      behavior-modification programs by 7%, and projects with the participation of
      local communities by only 3%. CONCLUSIONS: The majority of occupational medicine
      physicians do not implement the workplace health promotion in line with the
      modern concept of activities in this domain. They focus more on health education
      and medical prophylactics. There is a need to provide this group of physicians
      with a comprehensive training to develop their skills to initiate and coordinate
      setting-oriented projects and thus advance their activities in this field.

PMID- 15493498
TI  - [Health behavior and its rational in the perception of employees in medium-size
      and large companies].
AB  - BACKGROUND: The paper presents beliefs of employees working in Polish medium-size
      and large enterprises concerning the most essential aspects of healthy lifestyles
      and reasons for undertaking particular activities. MATERIALS AND METHODS: In the
      study, carried out in 2002, questionnaire-based interviews were taken in a group
      of 1134 employees of 250 Polish enterprises employing 100 or more workers.
      RESULTS: The following forms of taking care of one's own health were perceived by
      the respondents as the best ones: healthy nutrition (68%); physical activity and
      fitness (46%); adequate rest and relaxation (45%); coping with stress (35%); and
      regular health checkups (34%). There are various reasons why respondents
      undertake particular activities. Among them willingness to take care of their own
      good health (79%); maintaining fitness (72%); and enhancing work ability (67%)
      were most frequently reported. Ill health and illness were less often mentioned
      (57% and 43%, respectively). Taking care of health is rather motivated by the
      will to avoid the dependence on negatively perceived health care institutions
      than by fear of discomfort due to ill health or occurrence of an illness. Health
      enhancing activities are more often undertaken by better educated, wealthier and
      younger people, while in case of illness, the opposite groups become more active.
      CONCLUSIONS: Social differences in motivation for healthy behaviors stress the
      need to apply various methods in health promotion programs to be able to
      influence target social groups.

PMID- 15493499
TI  - [Management of cytostatic drugs by nurses: analysis of preliminary results].
AB  - BACKGROUND: Cytostatic drugs pose a quite specific occupational risk to health
      care workers. There is a wide range of potential harmful effects, including
      remote effects, exerted by this group of drugs. In Polish and international
      regulations, standards of work safety and hygiene concerning these substances are
      clearly defined. Nevertheless working conditions in Polish health care
      institutions are now mostly influenced by economic and organizational problems,
      which may also be reflected in the compliance with the work safety rules. This
      paper presents a preliminary analysis of subjective assessment of practice with
      regard to the management of cytostatics reported by nurses, an occupational group
      mostly exposed to these substances. MATERIALS AND METHODS: The study was carried
      out at hospital departments in the Warminsko-Mazurskie Voivodship, where exposure
      of the staff to these drugs was observed. The study covered the whole nursing
      staff exposed. Completed questionnaires were obtained from 60 nurses, aged +/- 32
      years (20-54 years) with job seniority +/- 8 years (2-18), including 58 nurses
      with secondary education and two university graduates. RESULTS AND CONCLUSIONS:
      Undergraduate education did not develop in respondents skills to work with
      cytostatics. There is a need to increase the involvement of nursing schools,
      research institutes and teaching hospitals in the improvement of vocational
      training of nurses working with cytostatic drugs. To this end, all nurses should
      be covered with the obligatory training how to handle this group of drugs. The
      respondents reported that they had acquired their knowledge and experience of
      managing cytostatics in their work and during training organized at workplace.
      Despite the acquired knowledge and experience the interviewed nurses did not
      always comply with work safety and hygiene regulations. The problem of exposure
      to cytostatic drugs in the form of tablets was most frequently neglected. Some of
      the nurses were additionally exposed to ionizing radiation. Shortage of the
      nursing staff may be one of the reasons for the observed negligence of safety
      regulations. This may suggest the need to set norms on the adequate number of
      personnel employed in departments where cytostatics are used. Patients treated
      with cytostatic drugs should be informed about the purpose of preventive measures
      taken by nurses.

PMID- 15493500
TI  - [Health reasons for work disability among persons before going into early
      retirement].
AB  - BACKGROUND: The demographic situation in Poland shows a progressive ageing of its
      population and a concomitant decrease in the number of people of the productive
      age. The identification of health problems in older groups of people of the
      productive age is essential for gaining better knowledge of measures to be taken
      in order to extend the period of occupational activity in this groups of workers.
      The aim of the study was to define the health status of persons going into early
      retirement on the basis of their sickness absence history covering the five
      preceding years. MATERIALS AND METHODS: The study was conducted among workers,
      aged over 45 years and below the retirement age, employed at production posts or
      operating production processes. The analysis covered 303 workers who went into
      early retirement in the years 1996-2000 and 485 persons in the same age group,
      but still employed. Information on the health causes of their disability to work
      during a five-year period was collected for both groups of persons. The temporary
      work disability was analyzed using the following parameters: sickness absence
      rate, sickness absence cases and the average duration of sickness absence.
      RESULTS: The study showed that the total sickness absence among persons going
      into early retirement during the preceding five years was 64% for men (sickness
      absence rate--18.56) and 14% for women (sickness absence rate--15.97), and it was
      higher compared to still employed persons. These differences were mostly observed
      in the group of diseases of the nervous system and sense organs (over twofold
      difference in men and about 58% in women), diseases of the circulatory and
      respiratory systems in men and diseases of the genitourinary system in women
      (about twofold difference). The main causes of sickness absence were: diseases of
      the circulatory (29% of male and 16% of female sickness absence), musculoskeletal
      (19 and 17%, respectively), and respiratory (15 and 19%, respectively) systems,
      as well as diseases of the nervous system and sense organs (15% of male sickness
      absence) and neoplasms (12% of female sickness absence). CONCLUSIONS: The results
      of the study indicate that in the older group of workers, health problems are one
      of the major causes of going into retirement before reaching the retirement age.

PMID- 15493501
TI  - [Moulds--occupational and environmental hazards].
AB  - This paper reviews the most common health effects of exposure to moulds.
      Allergens of mould may induce rhinitis or bronchial asthma, whereas occupational
      exposure frequently leads to hypersensitivity pneumonitis. Moulds also reveal
      cancerogenic and neurotoxic properties. They may cause serious infections,
      organic dust toxic syndrome and sick building syndrome. Methods used to evaluate
      exposures and decrease concentrations of spores in the house environment are also
      presented.

PMID- 15493502
TI  - [Protection of health care personnel from occupational exposure to blood borne
      pathogens: problems in legislative and other documents adopted in different
      countries].
AB  - Contact with human blood is one of the vital issues concerning occupational
      exposure to biological factors. The fact that pathogens that create high health
      risk may be transmitted by blood must not be ignored. Considering the problem of
      biological exposure at workplace, HIV, HBV and HCV are recognized as the most
      essential viruses. Health care workers belong to the occupational group
      characterized by the most frequent contact with blood. Infections induced by
      blood borne pathogens are mostly observed among nurses, laboratory personnel and
      physicians. In the European Union countries, the USA and Canada, there are
      relevant legal regulations pertaining to the management of potentially dangerous
      biological materials, whereas in Poland such regulations have not as yet been
      developed. Poland's accession to the European Union in 2004, commits the Polish
      government to harmonize Polish and European Union legislation also in this
      regard.

PMID- 15493503
TI  - [Current use of pesticides in Poland and the risk of reproductive disorders].
AB  - Among numerous factors typical of occupations in agriculture, pesticides occupy a
      specific place. Their hazardous effects may be manifested among others by
      reproductive disorders. Therefore, it is very important to know what kind of
      pesticides is used in both agriculture and greenhouses. The aim of the study was
      to review the kinds and amounts of pesticides used in agriculture and
      greenhouses. The review was performed in the Kujawsko-pomorskie voivoship and on
      14 horticulture farms. Their selection was based on the register of the Polish
      Horticulture Chamber. The pesticides were classified into two groups: those
      containing reproductive and/or developmental toxins (RD) and those acting as
      endocrine disrupters (ED). The majority of pesticides used in agriculture and
      horticulture belong to one of those groups. The results of the review suggest
      that the awareness of potential adverse effects of pesticides on fertility and
      pregnancy outcome should be increased among workers occupationally exposed to
      pesticides.

PMID- 15493504
TI  - [Primary prevention in workers exposed to ultraviolet radiation and radiation
      related risks].
AB  - This paper presents current views on the principles of primary prevention of
      ultraviolet radiation. Preventive interventions aimed at limiting exposure to
      solar light as well as cosmetics with adequate filters are one of the elements of
      work safety that should be ensured by employers. New generation of cosmetics
      contain several substances, including absorbing and chemical filters, and thus
      ensure effective protection against ultraviolet solar radiation with relatively
      low risk of adverse body effects. Application of several filters (physical and
      chemical) in one cosmetic provides an adequate skin protection. The issue to be
      thoroughly analyzed is the minimum amount of the used cosmetic to ensure
      effective protection against ultraviolet radiation.

PMID- 15493505
TI  - [Allergy to cosmetics. II. Preservatives].
AB  - Disinfectants are essential components of body care preparations, household goods
      and industrial products. They inhibit growth of bacteria and fungi. Esters of
      parahydroxybenzoate acid and products that release small amounts of formaldehyde
      (Germal 115, Germal II, Dovicil 200, Bronopol, DMDM hydantoine) were most
      frequently used in the past. In the 1980s, Katon CG (5-chloro-2-methyl-4
      isothiazolin-3-one + 2-methyl-4-isothiazolin-3-one) evoked the epidemics of
      contact dermatitis in Sweden, Finland, Germany, Italy and The Netherlands. In the
      next years, allergy to another preservative, Euxyl K 400 was dramatically
      growing. Studies carried out in 11 European countries showed that
      hypersensitivity increased from 0.7% in 1991 to 3.5% in 2000. It was revealed
      that not only cosmetics left on the skin sensitize, but also those washable.
      Apart from preservatives, allergic reactions are induced by emulgators,
      antioxidants, moisteners, lubricants, stabilizers and stickers.

PMID- 15493506
TI  - Cooperativity between selectins and beta2-integrins define neutrophil capture and
      stable adhesion in shear flow.
AB  - A cooperative, sequential process of molecular recognition governs leukocyte
      capture, rolling, and arrest on inflamed endothelium. Flowing neutrophils are
      captured via heterotypic adhesive interactions mediated by endothelial E
      selectin, whereas homotypic interactions between neutrophils are mediated by L
      selectin. To elucidate how each selectin facilitates the transition to CD18
      mediated stable adhesion, E-selectin and L-selectin were expressed at defined
      site density in a murine pre-B-cell line. Direct observation of two-body
      collisions revealed that 30% of neutrophil interactions with E-selectin
      transfectants formed doublets at low shear rate G = 14 s(-1) whereas a threshold
      shear rate 14 s(-1) < or = G < or = 10 s(-1) was necessary for L-selectin
      adhesion. Adhesion via L-selectin resisted rupture at high shear stress, while E
      selectin tethered doublets remained intact longer once formed. Moreover, higher
      expression of L-selectin (1100 sites/microm2) than that of E-selectin (220
      sites/microm2) was required for comparable heterotypic adhesion efficiency. With
      a threefold rise in active CD18 upregulated on chemotactically stimulated
      neutrophils, homotypic adhesion efficiency increased 10-fold compared to less
      than 5-fold for heterotypic adhesion to selectin transfectants. Co-expression of
      E-selectin and ICAM-1 boosted adhesion efficiency threefold more than either
      receptor alone over the range of active CD18 expression. These data are the first
      to quantify adhesion efficiency mediated by selectin tethering and conformational
      activation of beta2-integrin in neutrophils in shear flow.

PMID- 15493507
TI  - Role of the Pyk2-MAP kinase-cPLA2 signaling pathway in shear-dependent platelet
      aggregation.
AB  - Mechanisms of shear-induced platelet aggregation are not established. Data that
      ristocetin-induced von Willebrand factor (VWF) binding to glycoprotein (Gp)
      Ibalpha activates proline-rich tyrosine kinase 2 (Pyk2) and extracellular
      regulated kinase (ERK) has led to speculation that these events are coupled and
      that a MAP kinase may activate cytosolic phospholipase A2 (cPLA2)-mediated
      arachidonic acid (AA) release. To test this hypothesis and clarify the role of AA
      metabolism in shear-induced VWF-dependent platelet aggregation, we examined Pyk2,
      ERK1/2, and p38 phosphorylation, and arachidonic acid release and metabolism in
      platelets subjected to pathological shear stress in vitro. We observe tyrosine
      phosphorylation of Pyk2, p38, and ERK1/2 but no measurable increase in free AA,
      12-hydroxyeicosatetraenoic acid, or thromboxane A2. Inhibitors of ERK, p38, or
      cyclooxygenase activation fail to affect shear-induced platelet aggregation. When
      washed platelets are aspirin-pretreated, arachidonic acid release becomes
      measurable and aggregation at 60 and 120 s is attenuated. These data indicate
      that shear-induced VWF binding to platelet GpIb-IX-V activates Pyk2, ERK1/2, p38,
      and cPLA2, but that the magnitude of these responses is below the threshold
      needed to enhance shear-induced VWF-dependent platelet aggregation in the
      presence of plasma. These results provide a mechanistic basis for the long
      standing observation that shear-dependent platelet aggregation is unaffected by
      the antiplatelet drug aspirin.

PMID- 15493508
TI  - Cardiac optical mapping under a translucent stimulation electrode.
AB  - Major effects of stimulation on cardiac transmembrane potentials (Vm) are thought
      to occur under the electrode, however these have not been optically mapped due to
      blockage of light by electrodes. Here we optically mapped under translucent
      indium tin oxide (ITO) electrodes in hearts stained with transmembrane voltage
      sensitive fluorescent dye, di-4-ANEPPS excited at 488 nm. Emissions in wavelength
      bands 510-570 nm and >590 nm were similarly affected by changes in ITO
      transmittance due to electrochemical effects of current at the electrode
      interface. Dual-wavelength ratiometric mapping with the two emission bands
      revealed Vm under the electrode during plateau-phase stimulation (220 mA).
      Changes in Vm were heterogeneous under the electrode, and were anisotropic with
      larger values along the fiber axis. These results explain early excitation sites
      for sufficiently strong diastolic stimulation, and agree with theoretical
      predictions based on summation of anisotropic effects of point stimulation and a
      linear 3-d cardiac bidomain computer model. The bidomain model and experiments
      disagree under the edge of the electrode, where modeled Vm is much larger. Thus,
      changes in Vm under an electrode are anisotropic with greater Vm in the direction
      parallel to fibers. Nonlinear effects of stimulation in hearts may limit changes
      in Vm under the electrode edge.

PMID- 15493509
TI  - The effect of heart rate, preload, and afterload on the viscoelastic properties
      of the swine myocardium.
AB  - Experiments were performed to test the hypothesis that viscoelastic properties of
      the swine myocardium are independent of heart rate (HR), preload (PL), and
      afterload (AL). Left ventricular pressure and aortic flow (AoF) waveforms were
      recorded in 13 swine. At different paced heart rates, an inferior vena caval
      occlusion (IVC) was used to reduce PL, then the IVC was released and
      simultaneously the aorta was clamped to increase AL. Equivalent left ventricular
      pressure waveform pairs consisting of an ejecting waveform (denoted as LVP) and
      isovolumic waveform (denoted as hydromotive pressure, HMP) were selected
      according to specified criteria resulting in 371 equivalent waveform pairs. From
      the selected waveform pairs and corresponding aortic flow waveforms, the
      viscoelastic properties (k and epsilon1) were estimated by HMP = LVP + epsilon1
      V(EJ) + k x LVP x AoF. Here epsilon1 is the parallel elastance, k is the
      myocardial friction, and V(EJ) is the integral of AoF over ejection. Next, using
      k, epsilon1, LVP, and AoF waveforms, HMP was estimated using the equation above.
      To validate the model, the measured HMP and model-calculated HMP were compared
      for 371 matched waveform pairs (R2 = 0.97, SEE = 3.7 mmHg). The viscoelastic
      parameters (k and epsilon1) did not exhibit any clear or predictable dependence
      on HR, PL, and AL.

PMID- 15493510
TI  - Shear modulus of elasticity of the esophagus.
AB  - Experimental and diagnostic procedures like distension of a balloon catheter,
      bougie, and esophagogastroduodenoscopy can induce shear deformation in the
      esophageal wall. However, the shear modulus of the esophagus is yet unknown. The
      aim of this study was to determine the esophageal shear modulus and its
      dependence on the circumferential and longitudinal stresses and strains in the
      rat. The constitutive equation including the shear deformation based on a pseudo
      strain-energy function was generated. Results were obtained using a new triaxial
      instrument to perform simultaneous torsion, inflation, and longitudinal
      stretching tests. The shear modulus varied with the inflation pressure and the
      longitudinal stretch ratio. The shear modulus at the longitudinal stretch ratio
      of 1.5 and between inflation pressures of 0 and 2.0 kPa ranged from 5.43 to
      185.01 kPa. The mechanical constant of the esophagus showed that the esophageal
      wall was anisotropic with different stiffness in the circumferential,
      longitudinal, and the shear directions. The stiffness in the longitudinal
      direction was higher than in the circumferential direction (P < 0.001). This test
      can be extended for further mechanical remodeling experiments and for other
      tubular organs such as the small intestine or blood vessels.

PMID- 15493511
TI  - Biaxial testing of human annulus fibrosus and its implications for a constitutive
      formulation.
AB  - Internal pressure in the healthy human annulus fibrosus leads to multiaxial
      stress in vivo, yet uniaxial tests have been used exclusively to characterize its
      in vitro mechanical response and to determine its elastic strain energy function
      (W). We expected that biaxial tension tests would provide unique and necessary
      data for characterizing the annular material response, and thereby, for
      determining W. We performed uniaxial and biaxial tests on specimens of annulus,
      then developed an objective methodology for defining an appropriate form for W
      that considers data from multiple experiments simultaneously and allows the data
      to dictate more directly the form and the number of parameters needed. We found
      that the stresses attained in the biaxial tests were higher, while the strains
      were considerably lower, than those observed in the uniaxial tests. A comparison
      of strain energy functions determined from the different data sets demonstrated
      that constitutive models derived from uniaxial data could not predict annulus
      behavior in biaxial tension and vice versa. Since the annulus is in a state of
      multaxial stress in vivo, we conclude that uniaxial tests alone are insufficient
      to prescribe a physiologically relevant W for this tissue.

PMID- 15493512
TI  - Sinusoidal modeling of ictal activity along a thalamus-to-cortex seizure pathway
      I: new coherence approaches.
AB  - Understanding associations in neuronal circuitry is critical for tracing epilepsy
      pathways. Two new methods of measuring coherence between field potentials and EEG
      channels are proposed for modeling the level of linear association between
      channels during epileptic seizures. These methods rely upon modeling the
      repetitive clonic seizure activity as a sum of sinusoids with varying degrees of
      phase locking. Estimating the amplitude of sinusoids from correlation and cross
      correlation time domain data, we can find the coherences from a ratio of these
      amplitudes. One method utilizes amplitude finding from the multiple signal
      classification (MUSIC) technique. The other method uses alterations in amplitude
      of individual sinusoids and their ratios in a matrix pencil equation formed from
      cross- and auto-correlation matrices. The corresponding generalized eigenvalues
      of these equations form the coherence ratios. This utilizes the estimation of
      signal parameters using rotational invariance techniques (ESPRIT) algorithm to
      arrive at coherence amplitude ratios. Simulations illustrate that the MUSIC
      method provides better noise immunity as it out-performs the conventional Fourier
      transform-based method for coherence estimation. Both coherence estimators
      reflect presence of sinusoidal components that are propagated or not propagated
      along a particular transmission pathway. We illustrate the value of both methods
      by examining the strength of correlation between seizure EEG from specific
      thalamic nuclei and cortex in a rodent model of generalized epilepsy. The
      pentylenetetrazol (PTZ) chemoconvulsant model in rats reflects selective
      activation of the anterior thalamic nucleus. Using both methods, this neuronal
      element has much larger coherence with cortex than another thalamic region, the
      posterior thalamus (p < 0.05). These methods isolate the unique contribution of
      anterior thalamus in the formation of an ictal network and corroborate earlier
      conventional or periodogram techniques.

PMID- 15493513
TI  - Spatiotemporal encoding of a bar's direction of motion by neural ensembles in cat
      primary visual cortex.
AB  - Directionally selective neurons strongly fire when presented with a preferred
      direction of motion of a bar and only weakly respond otherwise. Intuition
      suggests these "specialist" neurons would be better suited to report this
      stimulus feature to higher visual centers than "generalist" neurons, neurons that
      broadly modulate their activity to the feature. However, as stimuli are encoded
      not by one cell but by large neural ensembles, we have studied the role of single
      cell receptive field properties in stimulus representation. Using regression
      error statistics, we compared the performance of direction-of-motion estimators,
      using ensembles of neurons selectively responding to direction of motion and
      estimators using ensembles not specializing to direction. We found that direction
      selective ensembles were no better at representing a bar's direction of motion
      than nonselective ensembles. Quite the opposite, the nonselective unit ensembles
      provided a better estimate of the direction (standard deviation of the error of
      33 degrees) than the direction-selective ensembles (standard deviation of the
      error of 42 degrees). The nonselective neurons provided information through a
      latency code that is apparent only when a neuron's activity is considered in the
      context of the responses of neighboring neurons. These results suggest that
      models utilizing both generalist and specialist neurons may better reflect the
      encoding mechanisms that take place in sensory pathways.

PMID- 15493514
TI  - Active iris mechanics and pupillary block: steady-state analysis and comparison
      with anatomical risk factors.
AB  - Primary angle-closure glaucoma arises when the iris physically obstructs outflow
      of aqueous humor, increasing the intraocular pressure and damaging the optic
      nerve. Pupillary block, the predominant mechanism for angle closure, is believed
      to be driven by mechanical interaction between the aqueous humor and the iris. We
      performed steady-state simulations of this coupled fluid-solid system, including
      an active sphincter to control pupil constriction. Model results compared
      favorably against Mapstone's pupil-blocking force analysis. We also evaluated
      anatomical risk factors and quantified their contributions to pupillary block and
      angle closure. The results showed that greater lens curvature and shorter iris
      zonule distance contribute significantly to pupillary block and the associated
      narrowing of the angle. Surprisingly, the model predicted that maximum pupillary
      block and angle closure occur at the minimum pupil dilation, contradicting the
      clinical observation that angle closure is most severe in dark conditions. This
      discrepancy suggests the involvement of one or more phenomena not captured by our
      current model.

PMID- 15493515
TI  - Interaction among humoral and neurogenic mechanisms in ventilation control during
      exercise.
AB  - The control of ventilation during exercise is analyzed by a mathematical model.
      It represents a significant improvement of our previous work, including the
      effect of potassium on peripheral chemoreceptors, a fast and a slow neurogenic
      component, and a more accurate description of blood flow control. Moreover, the
      feedforward contributions (potassium and neurogenic) have been incorporated
      within a larger model of feedback ventilatory control by central and peripheral
      chemoreceptors to O2 and CO2 changes, and the interaction among the different
      mechanisms in ventilation control have been analyzed during moderate (100 W) and
      severe (300 W) exercise. Results suggest that ventilatory changes during exercise
      can be mostly ascribed to feedforward neurogenic mechanisms, which ensure quite
      constant levels of arterial oxygen and CO2 pressure, thus avoiding the
      involvement of feedback mechanisms. Potassium plays a mild role in ventilation
      control during steady-state conditions. However, it may have a role in the
      transient phase after the onset of severe exercise, allowing a faster attainment
      of the final steady-state ventilation level. In agreement with the physiological
      literature, the model evidences the presence of three distinct kinetic components
      in V(E), which ensue from the temporal superimposition (sometimes antagonistic
      sometimes synergistic) among the several incorporated mechanisms.

PMID- 15493516
TI  - Assessing convergence of Markov chain Monte Carlo simulations in hierarchical
      Bayesian models for population pharmacokinetics.
AB  - Advances in computer hardware and the associated computer-intensive algorithms
      made feasible by these advances [like Markov chain Monte Carlo (MCMC) data
      analysis techniques] have made possible the application of hierarchical full
      Bayesian methods in analyzing pharmacokinetic and pharmacodynamic (PK-PD) data
      sets that are multivariate in nature. Pharmacokinetic data analysis in particular
      has been one area that has seized upon this technology to refine estimates of
      drug parameters from sparse data gathered in a large, highly variable population
      of patients. A drawback in this type of analysis is that it is difficult to
      quantitatively assess convergence of the Markov chains to a target distribution,
      and thus, it is sometimes difficult to assess the reliability of estimates gained
      from this procedure. Another complicating factor is that, although the
      application of MCMC methods to population PK-PD problems has been facilitated by
      new software designed for the PK-PD domain (specifically PKBUGS), experts in PK
      PD may not have the necessary experience with MCMC methods to detect and
      understand problems with model convergence. The objective of this work is to
      provide an example of a set of diagnostics useful to investigators, by analyzing
      in detail three convergence criteria (namely the Raftery and Lewis, Geweke, and
      Heidelberger and Welch methods) on a simulated problem and with a rule of thumb
      of 10,000 chain elements in the Markov chain. We used two publicly available
      software packages to assess convergence of MCMC parameter estimates; the first
      performs Bayesian parameter estimation (PKBUGS/WinBUGS), and the second is
      focused on posterior analysis of estimates (BOA). The main message that seems to
      emerge is that accurately estimating confidence regions for the parameters of
      interest is more demanding than estimating the parameter means. Together, these
      tools provide numerical means by which an investigator can establish confidence
      in convergence and thus in the estimated parameters derived from hierarchical
      full Bayesian pharmacokinetic data analysis.

PMID- 15493517
TI  - How do we accurately measure foot motion?

PMID- 15493518
TI  - Effects of taping on pain and function in patellofemoral pain syndrome: a
      randomized controlled trial.
AB  - STUDY DESIGN: A randomized controlled trial. OBJECTIVES: To investigate the
      effectiveness of daily patella taping and exercise on pain and function in
      individuals with patellofemoral pain syndrome. BACKGROUND: Patella taping and
      muscle-strengthening programs are commonly used to treat patellofemoral pain
      syndrome. There is, however, little evidence for the effectiveness of these
      approaches. METHODS AND MEASURES: Twenty-four men and 6 women aged 17 to 25 years
      (mean +/- SD, 18.7 +/- 1.2 years) participated in the study. Subjects were
      randomly and exclusively assigned to 1 of 3 treatment groups: patella taping
      combined with a standardized exercise program, placebo patella taping and
      exercise program, or exercise program alone (n = 10 in each group). Taping was
      applied and exercises performed on a daily basis for 4 weeks. Outcome measures
      were visual analog scales for pain and the functional index questionnaire,
      recorded at weekly intervals by a therapist who was blinded to group allocation.
      RESULTS: Separate mixed-model ANOVAs, with repeated measures on time, indicated
      statistically significant improvements in pain and function over time for all
      groups (P<.01) and also significant differences between groups for all measures
      (P<.01). Separate independent samples t tests showed that the group receiving
      taping and exercises had better pain and function scores following treatment than
      the placebo taping-and-exercise group and the exercise-alone group. There were no
      significant differences between the placebo taping-and-exercise group and
      exercise-alone group at any time point. CONCLUSIONS: These findings indicate that
      over a period of 4 weeks a combination of daily patella taping and exercises was
      successful in improving pain and function in individuals with patellofemoral pain
      syndrome. The combination of patella taping and exercise was superior to the use
      of exercise alone.

PMID- 15493519
TI  - Management of whiplash-associated disorder addressing thoracic and cervical spine
      impairments: a case report.
AB  - STUDY DESIGN: Clinical case report. OBJECTIVES: To describe a physical therapy
      program addressing impairments of the upper thoracic and cervical spine region
      for an individual with a whiplash-associated disorder. BACKGROUND: A 32-year-old
      female with complaint of diffuse posterior cervical and upper thoracic region
      pain was evaluated 2 weeks following a motor vehicle accident. The patient
      reported that she was unable to sit for longer than 10 minutes or perform
      household duties for longer than 1 hour. In addition, she was unable to perform
      her tasks as a postal worker or participate in her customary running and aerobic
      exercise activities because of pain in the cervical and upper thoracic region.
      METHODS AND MEASURES: An examination for physical impairments was performed,
      including the measurement of cervical range of motion using the CROM device, and
      the assessment of soft tissue and segmental mobility of the upper thoracic and
      cervical spine regions. The Northwick Park Neck Pain Questionnaire was used to
      assess functional limitations and disability. Manual therapy and therapeutic
      exercises were applied to address the identified impairments. Manual therapy
      techniques included soft tissue mobilization, joint mobilization, and joint
      manipulation. RESULTS: The patient's cervical range of motion was improved and
      the disability score improved from 25% to 19.5% 3 days after the initial session
      addressing the thoracic spine. Following a second session also addressing
      thoracic spine impairments and the use of therapeutic exercises for 7 days, the
      disability score improved to 11.1%. At the final visit 17 days following the
      third visit, which focused on addressing the cervical spine impairments, there
      was complete resolution of signs and symptoms and disability. CONCLUSIONS:
      Interventions addressing the impairments of the upper thoracic and cervical spine
      region were associated with reducing pain, increasing cervical range of motion,
      and facilitating return to work and physical activities in a patient with a
      whiplash-associated disorder. There is a need for continued research
      investigating the efficacy of providing interventions to the thoracic spine for
      patients with whiplash-related injuries.

PMID- 15493520
TI  - Differences in measurements of lumbar curvature related to gender and low back
      pain.
AB  - STUDY DESIGN: Cross-sectional. OBJECTIVES: To test the assumption that postural
      alignment and gender have a bearing on the specific type of low back pain (LBP) a
      person manifests. BACKGROUND: Measurements of static sagittal lumbar curvature
      are used by clinicians in the management of patients with LBP, but no
      investigator has reported differences in curvature related to specific categories
      of LBP. METHODS AND MEASURES: We used a computer-interfaced, 3-D,
      electromechanical digitizer to derive curvature angles for the region of the
      spine between T12-L1 and S2. Trained clinicians examined the subjects and
      determined their LBP diagnoses. We used t tests to examine differences in
      curvature between women and men, those with and those without LBP, and those in 4
      different categories of LBP. We used chi2 to examine the relationship between
      gender and LBP category. RESULTS: Lumbar curvature angle (lordosis) was 13.2
      degrees larger for women than for men (t = 6.74; P<.01). There was no difference
      in lumbar curvature between people with undifferentiated LBP and people without
      LBP. There were differences in lumbar curvature between people in various
      categories of LBP, for example, subjects in the lumbar-rotation-with-extension
      category had 8.4 degrees more lumbar curvature than subjects in the lumbar
      rotation-with-flexion category (t = 2.16; P<.05). Based on the frequency
      distributions, there was a significant relationship between gender and LBP
      category (chi2 = 10.19; P<.01). CONCLUSIONS: Measurements of lumbar curvature
      should be expected to differ between men and women and may be related to
      different types of low back pain.

PMID- 15493521
TI  - Effectiveness of manual physical therapy, therapeutic exercise, and patient
      education on bilateral disc displacement without reduction- of the
      temporomandibular joint: a single-case design.
AB  - STUDY DESIGN: Single-case A1-B-A2 design. OBJECTIVE: To determine if manual
      physical therapy, therapeutic exercise, and patient education would be an
      effective management strategy for a patient with a disc displacement without
      reduction of both temporomandibular joints. BACKGROUND: A number of conservative
      management strategies have been proposed for the treatment of temporomandibular
      disorders. However, little evidence exists to indicate the effectiveness of
      physical therapy interventions in patients with bilateral disc displacement
      without reduction. METHODS AND MEASURES: Phase A1 of the study consisted of a
      baseline condition in which no intervention was initiated. Phase B included
      manual physical therapy, therapeutic exercise, and patient education focusing on
      the temporomandibular joint and cervical spine. Phase A2 consisted of withdrawal
      of the intervention. The Steigerwald/Maher disability questionnaire was used to
      collect data relative to function. A visual analog scale was used to collect pain
      data and maximal mouth opening measurements were obtained as an indicator of
      range of motion. Visual analysis and the 2 standard deviation band method of
      statistical analysis were used to compare data. RESULTS: Following the
      implementation of the intervention phase, the patient demonstrated significant
      reductions in pain and improvements in maximal mouth opening and function as
      measured by the Steigerwald/Maher disability questionnaire. These observed
      improvements were maintained at the time of a 3-month follow-up. CONCLUSIONS: The
      results of our study suggest that manual physical therapy, therapeutic exercise,
      and patient education may have been an effective management strategy for a
      patient with bilateral disc displacement without reduction of the
      temporomandibular joints. Further outcome studies in the form of randomized
      controlled trials are needed to determine the clinical utility of this treatment
      approach in a larger population.

PMID- 15493522
TI  - Paraspinal musculature and skin temperature changes: comparing the Thermacare
      HeatWrap, the Johnson & Johnson Back Plaster, and the ABC Warme-Pflaster.
AB  - STUDY DESIGN: Prospective, randomized, crossover design. OBJECTIVES: To compare
      the effectiveness of the Johnson & Johnson Back Plaster, the ABC Warme-Pflaster,
      and the ThermaCare HeatWrap on skin and paraspinal muscle temperature. Also, to
      compare the subjects' heat perception for the 3 products. BACKGROUND: Heat
      therapy is a common treatment for low back pain and disability. There are a
      number of products on the market that are suggested to relieve low back pain by
      providing warmth to the back; however, their effectiveness for increasing tissue
      temperature compared with heat sensation has not been tested. METHODS AND
      MEASURES: To measure paraspinal muscle temperature, 1 thermocouple monofilament
      was inserted into the paraspinal muscle 2 cm from the skin surface at the L3
      level using a 20-gauge 1.25-in (3.15-cm) sterile catheter. To measure skin
      interface temperature, 2 thermocouples were placed on the skin at distances of 5
      cm and 7 cm from the insertion site. The Isothermex was used to record
      temperatures to the nearest 0.1 degrees C for 120 minutes. The subjects also
      rated heat perception using a 10-cm visual analog scale at 0, 30, 60, 90, and 120
      minutes. Analysis of covariance models were used for statistical analysis.
      RESULTS: There was a significant product x time interaction (F14,231 = 3.77,
      P<.0001) at the intramuscular site, but there was not a significant product x
      time interaction (F14,231 = 1.03, P = .4228) at the skin site. Both the main
      effects for product (F2,33 = 41.59, P<.0001) and time (F3,51 = 19.02, P<.0001)
      were significant for the visual analog scale data. The ThermaCare HeatWrap
      produced significant increases in both skin and intramuscular temperatures with
      less heat sensation. The Johnson & Johnson Back Plaster and the ABC Warme
      Pflaster increased temperature at the skin surface and provided the greatest heat
      sensations, but they did not provide intramuscular heat. CONCLUSIONS: The
      ThermaCare HeatWrap is more effective at increasing temperature at a 2-cm depth
      with less perceived heat compared to the Johnson & Johnson Back Plaster and the
      ABC Warme-Pflaster. The latter 2 products provide a sensation of heat but do not
      actually provide a muscle temperature change at a depth of 2 cm.

PMID- 15493523
TI  - Foot and Ankle Research Retreat: concensus statement.
AB  - It is well recognized that the foot is a complex structure with 26 bones and over
      30 articulations. Measuring its mechanics is a formidable task that is usually
      accomplished with a simplification of the system. The papers presented at this
      meeting provided some of the most current research in the area of multisegment
      foot modeling. The scientific discussions were rich as the small, intimate, and
      collegial environment encouraged an open flow of ideas. It was acknowledged that
      much work is still needed in the development of foot models to improve the
      measurement of foot mechanics. However, there was a strong sentiment among the
      participants to begin to apply these models to clinical problems. It was
      suggested that this be the focus of the next Foot and Ankle Research Retreat.

PMID- 15493524
TI  - The foot: block, gearbox, or cushion? Some concepts in foot kinematics.

PMID- 15493525
TI  - One step at a time: lessons learned from cadaver simulations of locomotion.

PMID- 15493526
TI  - Ferulic acid: an antioxidant found naturally in plant cell walls and feruloyl
      esterases involved in its release and their applications.
AB  - Ferulic acid is the most abundant hydroxycinnamic acid in the plant world and
      maize bran with 3.1% (w/w) ferulic acid is one of the most promising sources of
      this antioxidant. The dehydrodimers of ferulic acid are important structural
      components in the plant cell wall and serve to enhance its rigidity and strength.
      Feruloyl esterases are a subclass of the carboxylic acid esterases that hydrolyze
      the ester bond between hydroxycinnamic acids and sugars present in plant cell
      walls and they have been isolated from a wide range of microorganisms, when grown
      on complex substrates such as cereal brans, sugar beet pulp, pectin and xylan.
      These enzymes perform a function similar to alkali in the deesterification of
      plant cell wall and differ in their specificities towards the methyl esters of
      cinnamic acids and ferulolylated oligosaccharides. They act synergistically with
      xylanases and pectinases and facilitate the access of hydrolases to the backbone
      of cell wall polymers. The applications of ferulic acid and feruloyl esterase
      enzymes are many and varied. Ferulic acid obtained from agricultural byproducts
      is a potential precursor for the production of natural vanillin, due to the lower
      production cost.

PMID- 15493527
TI  - Mechanisms prevalent during bioremediation of wastewaters from the pulp and paper
      industry.
AB  - Bioremediation of wastewaters represents an important treatment methodology,
      especially when examined against the backdrop of ever-stricter legislation that
      is evolving in order to regulate effluent release into the environment. It has
      been reported that bioremediation specifically holds promise in solving
      environmental problems. Crucial questions surrounding the treatment of effluents
      include: efficiency of the process, economic feasibility, legal requirements, and
      the mechanisms involved in the remediation process. Of all these issues
      mentioned, the last requires special attention. This paper investigates these
      matters and focuses on techniques that are currently employed to determine the
      efficiency of bioremediation and mechanisms involved therein. The physiological
      significance of biosorption is also examined, as this subject has not been fully
      addressed in previous publications.

PMID- 15493528
TI  - Phytoremediation--a novel and promising approach for environmental clean-up.
AB  - Phytoremediation is an eco friendly approach for remediation of contaminated soil
      and water using plants. Phytoremediation is comprised of two components, one by
      the root colonizing microbes and the other by plants themselves, which degrade
      the toxic compounds to further non-toxic metabolites. Various compounds, viz.
      organic compounds, xenobiotics, pesticides and heavy metals, are among the
      contaminants that can be effectively remediated by plants. Plant cell cultures,
      hairy roots and algae have been studied for their ability to degrade a number of
      contaminants. They exhibit various enzymatic activities for degradation of
      xenobiotics, viz. dehalogenation, denitrification leading to breakdown of complex
      compounds to simple and non-toxic products. Plants and algae also have the
      ability to hyper accumulate various heavy metals by the action of phytochelatins
      and metallothioneins forming complexes with heavy metals and translocate them
      into vacuoles. Molecular cloning and expression of heavy metal accumulator genes
      and xenobiotic degrading enzyme coding genes resulted in enhanced remediation
      rates, which will be helpful in making the process for large-scale application to
      remediate vast areas of contaminated soils. A few companies worldwide are also
      working on this aspect of bioremediation, mainly by transgenic plants to replace
      expensive physical or chemical remediation techniques. Selection and testing
      multiple hyperaccumulator plants, protein engineering ofphytochelatin and
      membrane transporter genes and their expression would enhance the rate of
      phytoremediation, making this process a successful one for bioremediation of
      environmental contamination. Recent years have seen major investments in the R&D,
      which have also resulted in competition of filing patents by several companies
      for economic gains. The details of science & technology related to
      phytoremediation have been discussed with a focus on future trends and prospects
      of global relevance.

PMID- 15493529
TI  - Utilization of enzymes for environmental applications.
AB  - Enzymes are powerful tools that help sustain a clean environment in several ways.
      They are utilized for environmental purposes in a number of industries including
      agro-food, oil, animal feed, detergent, pulp and paper, textile, leather,
      petroleum, and specialty chemical and biochemical industry. Enzymes also help to
      maintain an unpolluted environment through their use in waste management.
      Recombinant DNA technology, protein engineering, and rational enzyme design are
      the emerging areas of research pertaining to environmental applications of
      enzymes. The future will also see the employment of various technologies
      including gene shuffling, high throughput screening, and nanotechnology. This
      article presents an overview of the enzymatic applications in pollution control
      and the promising research avenues in this area.

PMID- 15493530
TI  - Imaging idiopathic generalized epilepsy.
AB  - It has been traditionally held that there is no radiological abnormality in
      patients with idiopathic generalized epilepsy (IGE). Sophisticated image
      processing and quantitative magnetic resonance imaging (MRI) studies suggest
      that, in some cases, there may be a subtle structural abnormality. Magnetic
      resonance spectroscopy indicates neuronal dysfunction with differing patterns of
      abnormality in the IGE sub-syndromes, and high levels of glutamate and glutamine
      have been suggested in the frontal lobes, and low GABA levels in the occipital
      lobe. Studies reflecting cerebral blood flow at the time of absences have given
      complex results. The principal consensus is of an increase in the thalamus and
      broad decreases in the neocortex, reflecting a suppression of neuronal activity,
      but with the possibility of some increases, that could perhaps reflect focal
      areas of neuronal activation. PET ligand studies with an opioid tracer have
      implied neocortical release of endogenous opioids at the time of serial absences.
      In combination with high time-resolution neurophysiological methods, static and
      dynamic PET studies with specific ligands have the potential to elucidate the
      functional anatomy and neurochemical circuits that under-lie IGE.

PMID- 15493531
TI  - Emergent electroencephalogram in the intensive care unit: indications and
      diagnostic yield.
AB  - Our aim was to study the frequency and reasons an emergent electroencephalogram
      (EmEEG) is ordered in the ICUs compared to the hospital ward, examine its
      usefulness and find predictive variables for its results. We retrospectively
      identified all electroencephalograms ordered between December 1997 and March 2002
      and performed within 1 hour. The tests ordered from four ICUs were compared with
      those ordered from the Ward beds, and predictive models were developed for the
      results based on clinical variables. We also compared the EmEEGs ordered by the
      Neuro-ICU to those from the other Units. The ICUs ordered 129 (49.4%) of all
      EmEEGs during the study period. The NICU ordered 32 tests. The most frequent
      reason for obtaining the test was to rule out status epilepticus (68.2%). The
      NICU ordered more frequently the test to exclude non-convulsive status than the
      other ICUs. Compared to non-ICU, ICU patients with head trauma or post
      cardiopulmonary arrest had more tests and patients with stroke fewer. Convulsive
      status epilepticus and generalized slowing were found more frequently in the
      ICUs, and normal EEG, interictal epileptiform activity or focal non-epileptic
      slowing were more frequent in the non-ICU cases. In at least 12.4% of ICU
      patients, the test was expected to lead to an anti-epileptic management change.
      Cardiopulmonary arrest and age were predictive of any epileptic activity on the
      EEG in ICU patients. In conclusion, in our institution EmEEG is ordered by the
      ICUs in two thirds of the cases to exclude status epilepticus. Although status
      epilepticus is confirmed more frequently in the ICUs than on the Ward, the most
      frequent finding remains generalized slowing, which is found in half of the ICU
      ordered EmEEGs. A conservative estimation is that EmEEG will lead to medication
      change in at least 1 out of 8 ICU patients. Cardioopulmonary arrest is predictive
      of epileptic activity and a prolonged EmEEG may also increase the yield.

PMID- 15493532
TI  - EEG in seizure prognosis: association of slow wave activity and other factors in
      patients with apparent misleading epileptiform findings.
AB  - Our previous study showed that patients with many spikes in their EEGs generally
      have uncontrolled seizures and those with no or rare spikes have controlled
      attacks. However, exceptions do exist, and this study was designed to determine
      what other aspects in the EEG could lead to the proper prognosis with these
      exceptions, rather than to an incorrect one. Two groups were assembled: 150
      patients with 674 EEGs with controlled seizures and 150 patients with 804 EEGs
      with uncontrolled attacks. Our data showed that the presence or absence of a slow
      wave abnormality usually led to a proper prognosis in these exceptional cases.
      The absence of any slow wave abnormality, but with many spikes was usually
      associated with controlled attacks and the presence of slowing, especially with
      delta slow waves, but without spikes, was more often seen in patients with
      uncontrolled attacks. The change in the number of spikes over time also led to a
      more accurate prognosis.

PMID- 15493533
TI  - Event-related potentials in young and elderly adults during a visual spatial
      working memory task.
AB  - The P300 event-related brain potential (ERP) was examined in 14 young (20-29
      years of age) and 16 elderly (60-82 years of age) subjects during the performance
      of a visuospatial memory task requiring recognition of locations. Elderly and
      young adults exhibited similar recognition accuracy, but recognition reaction
      times were significantly slower in the elderly. Midline P300 amplitudes recorded
      in response to visuospatial probe stimuli were significantly attenuated in the
      elderly, and, depending on the nature of the probe, P300 latency-derived indices
      indicated that both cognitive and motoric slowness characterized visuospatial
      recognition in the aged. The results, discussed in relation to neural mechanisms
      supporting working memory function, suggest that alterations in attention and
      processing speed may play a role in visual-spatial working memory deficits
      associated with normal and pathological aging.

PMID- 15493534
TI  - Auditory evoked responses in a comparison between schizophrenia patients with and
      without premorbid history of drug abuse: report of pilot results.
AB  - Evidence for a role for drugs of abuse in the development of chronic psychotic
      syndromes is scattered throughout 40 years of literature. Electrophysiological
      studies examining groups believed to have chronic drug-induced psychotic symptoms
      yielded interesting findings. To our knowledge, no studies directly compared
      schizophrenia patients whose drug use preceded and those whose drug use followed
      the onset of psychotic symptoms. Twenty-six schizophrenia patients and 10 healthy
      control subjects were recruited for the study. Based on the SCID interview,
      schizophrenia subjects were classified into a Psychosis First (Psy 1st) group
      (N=11), Drugs First (Drugs 1st; N=8), and No Drug Use (No Drugs; N=7).
      Schizophrenia subjects were administered the Positive and Negative Symptoms Scale
      (PANSS). The P300 evoked response and sensory gating were measured for all
      subjects. Despite the small sample sizes significant differences were found
      between the groups. Most significantly, the P300 amplitude was smallest in the
      Drugs 1st as compared to the No Drugs groups, while sensory gating deficit was
      worst in the Psy 1st group. The data suggest that significant clinical and
      electrophysiological differences between these groups can be identified. Further
      research to better define these differences seems warranted.

PMID- 15493535
TI  - The usefulness of quantitative EEG (QEEG) and neurotherapy in the assessment and
      treatment of post-concussion syndrome.
AB  - Mild traumatic brain injury (TBI) is associated with damage to frontal, temporal
      and parietal lobes. Post-concussion syndrome has been used to describe a range of
      residual symptoms that persist 12 months or more after the injury, often despite
      a lack of evidence of brain abnormalities on MRI and CT scans. The core deficits
      of post-concussion syndrome are similar to those of ADHD and mood disorders, and
      sufferers often report memory, socialization problems and frequent headaches.
      While cognitive rehabilitation and psychological support are widely used, neither
      has been shown to be effective in redressing the core deficits of post-concussion
      syndrome. On the other hand, quantitative EEG has been shown to be highly
      sensitive (96%) in identifying post-concussion syndrome, and neurotherapy has
      been shown in a number of studies to be effective in significantly improving or
      redressing the symptoms of post-concussion syndrome, as well as improving similar
      symptoms in non-TBI patients.

PMID- 15493536
TI  - How sleep was dissociated into two states: telencephalic and rhombencephalic
      sleep?

PMID- 15493537
TI  - The duality of sleep revealed: the history of paradoxical sleep.

PMID- 15493538
TI  - The paradox of sleep: the early years.

PMID- 15493539
TI  - Michel Jouvet: a personal tribute.

PMID- 15493540
TI  - Michel Jouvet: the enigma of scientific creativity.

PMID- 15493541
TI  - Slow-wave sleep: serotonin, neuronal plasticity, and seizures.
AB  - This article starts by enumerating several data that vindicate Michel Jouvet's
      hypothesis regarding serotonin as a factor promoting slow-wave sleep. The core of
      the article is devoted to the description of neuronal bases underlying sleep
      oscillations, with emphasis on the cortically generated slow oscillation (0.5-1
      Hz) that groups both low-frequency (spindles and delta) and high-frequency
      (beta/gamma) rhythms. The low-frequency rhythms are generated by the synchronous
      firing of cortical neurons during the depolarizing phase of the slow oscillation,
      which impacts on the thalamic circuitry to generate spindles and clock-like delta
      potentials. The fast activity is voltage-dependent and occurs during the
      depolarization component of the slow cortical oscillation. This coalescence of
      brain rhythms, discovered in intracellular studies of neocortical and thalamic
      neurons, is now supported by EEG studies during human sleep. The rich spontaneous
      activity of neocortical neurons during slow-wave sleep is associated with
      neuronal plasticity that may play a role in consolidating memory traces acquired
      during the state of waking. Surprisingly, neuronal plasticity, usually regarded
      as a beneficial phenomenon implicated in memory and learning, could develop
      during slow-wave sleep into self-sustained paroxysmal discharges, similar to
      spike-wave complexes that appear in some epileptic syndromes.

PMID- 15493542
TI  - Contribution of the "knock-out" technology to understanding the role of serotonin
      in sleep regulations.

PMID- 15493543
TI  - Paradoxical REM sleep promoting and permitting neuronal networks.
AB  - Since its electrophysiological identification in the 1950's, the state of REMS or
      PS has been shown through multiple lines of evidence to be generated by neurons
      in the oral pontine tegmentum. The perpetration of this paradoxical state that
      combines cortical activation with the most profound behavioral sleep occurs
      through interplay between PS-promoting (On) and PS-permitting (Off) cell groups
      in the pons. Cholinergic cells in the LDTg and PPTg promote PS by initiating
      processes of both forebrain activation and peripheral muscle atonia. Bearing
      alpha1-adrenergic receptors, cholinergic cells, which likely project to the
      forebrain, are excited by NA and active during both W and PS (W/PS-On), when they
      promote cortical activation. Bearing alpha2-adrenergic receptors, other
      cholinergic cells, which likely project to the brainstem, are inhibited by NA and
      thus active selectively during PS (PS-On), when they promote muscle atonia.
      Noradrenergic, together with serotonergic, neurons, as PS-Off neurons, thus
      permit PS in part by lifting their inhibition upon the cholinergic PS-On cells.
      The noradrenergic/serotonergic neurons are inhibited in turn by local GABAergic
      PS-promoting neurons that may be excited by ACh. Other similarly modulated
      GABAergic neurons located through the brainstem reticular formation become active
      to participate in the inhibition of reticulo-spinal and raphe-spinal neurons as
      well as in the direct inhibition of motor neurons. In contrast, a select group of
      GABAergic neurons located in the oral pontine reticular formation and possibly
      inhibited by ACh turn off during PS. These GABAergic PS-permitting neurons
      release from inhibition the neighboring large glutamatergic neurons of the oral
      pontine reticular formation, which are likely concomitantly excited by ACh. In
      tandem with the cholinergic neurons, these glutamatergic reticular neurons
      propagate the paradoxical forebrain activation and peripheral inactivation that
      characterize PS.

PMID- 15493544
TI  - Brainstem structures responsible for paradoxical sleep onset and maintenance.
AB  - This paper is dedicated to our mentor, Michel Jouvet who inspired our career and
      transmitted to us his passion for the study of the mechanisms responsible for
      paradoxical sleep genesis and also that of its still mysterious functions. We
      expose in the following the progresses in the knowledge in this field brought
      during 40 years by Michel Jouvet and his team and more recently by the members of
      a new CNRS laboratory in which we aim to pursue in the path opened by Michel
      Jouvet.

PMID- 15493545
TI  - Regional organisation of brain activity during paradoxical sleep (PS).
AB  - Human brain function is regionally organised during paradoxical sleep (PS) in a
      very different way than during wakefulness or slow wave sleep. The important
      activity in the pons and in the limbic/paralimbic areas constitutes the key
      feature of the functional neuroanatomy of PS, together with a relative quiescence
      of prefrontal and parietal associative cortices. Two questions are still
      outstanding. What neurocognitive and neurophysiological mechanisms may explain
      this original organization of brain function during PS? How the pattern of
      regional brain function may relate to dream content? Although some clues are
      already available, the experimental answer to both questions is still pending.

PMID- 15493546
TI  - Role of the locus coeruleus in the control of paradoxical sleep generation in the
      cat.

PMID- 15493547
TI  - Mechanisms and models of REM sleep control.
AB  - The first sections of this paper survey the history and recent developments
      relevant to the major neurotransmitters and neuromodulators involved in REM sleep
      control. The last portion of this paper proposes a structural model of cellular
      interaction that produces the REM sleep cycle, and constitutes a further revision
      of the reciprocal interaction model This paper proposes seven criteria to define
      a causal role in REM sleep control for putative neuro-transmitters/modulators.
      The principal criteria are measurements during behavioral state changes of the
      extracellular concentrations of the putative substances, and electrophysiological
      recording of their neuronal source. A cautionary note is that, while
      pharmacological manipulations are suggestive, they alone do not provide
      definitive causal evidence. The extensive body of in vivo and in vitro evidence
      supporting cholinergic promotion of REM sleep via LDT/PPT neuronal activity is
      surveyed. An interesting question raised by some studies is whether cholinergic
      influences in rat are less puissant than in cat. At least some of the apparent
      lesser REM-inducing effect of carbachol in the rat may be due to incomplete
      control of circadian influences; almost all experiments have been run only in the
      daytime, inactive period, when REM sleep is more prominent, rather than in the
      REM-sparse nighttime inactive period. Monoaminergic inhibition of cholinergic
      neurons, once thought to be the most shaky proposal of the reciprocal interaction
      model, now enjoys considerable support from both in vivo and in vitro data.
      However, the observed time course of monoaminergic neurons, their "turning off"
      discharge activity as REM sleep is approached and entered would seem to be
      difficult to produce from feedback inhibition, as originally postulated by the
      reciprocal interaction model. New data suggest the possibility that GABAergic
      inhibition of Locus Coeruleus and Dorsal Raphe monoaminergic neurons may account
      for the "REM-off" neurons turning off. However, the source(s) of GABAergic
      influences suggested by anatomical studies has yet to be definitively identified
      by electrophysiological recordings of GABAergic neurons that show the requisite
      inverse time course of activity relative to monoaminergic neurons. New and still
      preliminary microdialysis data suggest that reticular formation neurons, the
      effector neurons for REM sleep phenomena, might be disinhibited during REM sleep
      by decreased GABAergic influence, perhaps stemming from REM-on cholinergic
      neuronal inhibition of reticular formation GABAergic neurons. Whether the
      postulated cholinergic inhibition of GABAergic neurons is present is testable
      with in vitro recordings and double labeling. Taking into account the observed
      data on neuro-modulators/transmitters, a structural model incorporating
      interaction of REM-on and REM-off neurons and GABAergic influences is proposed.
      Finally, with respect to orexin and REM sleep, it is hypothesized that
      orexinergic activity may be a principal factor controlling REM sleep's absence
      from the active period in strongly circadian animals such as rat and man.

PMID- 15493548
TI  - Rem sleep without atonia--from cats to humans.
AB  - Basic science research observations often lead to unexpected surprises. It is
      likely that in 1965 when Dr. Michel Jouvet placed bilateral peri-locus coeruleus
      lesions in cats and observed REM sleep without atonia (RWA) and "oneiric"
      behavior that could only be explained by "acting out dreams" (or "dreaming out
      acts"), he recognized that it was an important observation, but had little
      inkling of its true significance. Nor could he even imagine that it would lead to
      such greater understanding of wake/sleep phenomena in humans. Likely also, the
      first observation of REM sleep behavior disorder (RBD) in humans was felt to be
      interesting and novel - again with no true appreciation of what this seemingly
      simple observation would lead to important clinical relationships with numerous
      neurodegenerative disorders. The identification of RBD in humans also buttressed
      the concept of state dissociation, which has served to explain many previously
      unexplainable human behavioral phenomena.

PMID- 15493549
TI  - Narcolepsy research: past, present, and future perspectives.
AB  - In 1877, Westphal described a patient with hypersomnia and episodic muscle
      weakness. He did not feel that these weakness attacks could simply be explained
      by "epileptoid" phenomenon. The next year, Fischer described a similar case. By
      1880, Gelineau decided that patients with these symptoms represented a distinct
      clinical entity and he called it "narcolepsy". In 1902, Loewenfeld noted the
      importance of cataplexy in this disorder, and in 1934 Daniels published an
      important review on the topic which helped to galvanize interest in further
      study. In 1957, Yoss and Daly discussed the "clinical tetrad" which included
      hypersomnia, cataplexy, hypnagogic hallucinations, and sleep paralysis. In 1960,
      Vogel noted that patients with narcolepsy had early onset of REM sleep on their
      electroencephalograms. At the First International Symposium on Narcolepsy in
      1975, the symptom of disturbed nocturnal sleep was added to the clinical
      diagnostic criteria for narcolepsy. For many years the etiology and mechanisms of
      this disease were poorly understood. It was not until the early 1970s when the
      exciting animal and human research first started to unravel the mysteries of the
      genetics and physiology of narcolepsy. This research will be discussed below.

PMID- 15493550
TI  - Posterior hypothalamus and regulation of vigilance states.

PMID- 15493551
TI  - Sleep-promoting functions of the hypothalamic median preoptic nucleus: inhibition
      of arousal systems.
AB  - Recent work supports the hypotheses developed by von Economo and Nauta and
      elaborated by Sallanon et al. that the POA contains a sleep-promoting output that
      opposes wake-promoting neuronal groups in the PH. The POA gives rise to
      descending pathways that terminate within wake-promoting populations in pLH, PH
      and midbrain. Current evidence suggests that this output originates in POA sleep
      active GABAergic neurons. This output also seems to convey the signals of
      homeostatic drive. Disynaptic projections from the SCN to both MnPN and VLPO were
      recently identified. These may regulate the circadian control of sleep
      propensity. The hypothesis that the descending projections from POA sleep-active
      neurons to sites of arousal-related neurons originates in GABAergic neurons must
      be confirmed. Also to be further clarified is the anatomical distribution of
      putative sleep-active GABAergic neurons within the POA. Segregated groups have
      been found in the MnPN and VLPO, but unit recording studies of sleep-active
      neurons, lesion studies and local neurochemical application studies all indicate
      that sleep-active neurons may be found diffusely in the POA and adjacent areas.
      The MnPN has been shown previously to be involved in water balance and blood
      pressure regulation and to be responsive to hyperthermia. Our studies suggest
      that this nucleus also contains sleep-active, putative sleep-promoting neurons.
      However, interactions between sleep control and physiological variables must be
      considered. In particular, the details of neuronal basis of the coupling of warm
      sensitive neurons in MnPN to the POA hypnogenic output has not been explored. It
      is also worth noting that both the VLPO and MnPN lie close to the ventricular and
      subarachnoid surface and are punctuated by radial arterioles. The possibility
      that the sleep-regulatory functions of these sites is coupled to physiological
      signals conveyed through epithelial cells has been suggested for the actions of
      PGD2 but has yet to be explored in detail for other putative hypnogens.

PMID- 15493552
TI  - The dynamics of spindles and EEG slow-wave activity in NREM sleep in mice.
AB  - A quantitative analysis of spindles and spindle-related EEG activity was
      performed in C57BL/6 mice. The hypothesis that spindles are involved in sleep
      regulatory mechanisms was tested by investigating their occurrence during 24 h
      and after 6 h sleep deprivation (SD; n = 7). In the frontal derivation distinct
      spindle events were characterized as EEG oscillations with a dominant frequency
      approximately at 11 Hz. Spindles were most prominent during NREM sleep and
      increased before NREM-REM sleep transitions. Whereas spindles increased
      concomitantly with slow wave activity (SWA, EEG power between 0.5 and 4.0 Hz) at
      the beginning of the NREM sleep episode, these measures showed an opposite
      evolution prior to the transition to REM sleep. The 24-h time course of spindles
      showed a maximum at the end of the 12-h light period, and was a mirror image of
      SWA in NREM sleep. After 6 h SD the spindles in NREM sleep were initially
      suppressed, and showed a delayed rebound. In contrast, spindles occurring
      immediately before the transition to REM sleep were enhanced during the first 2 h
      of recovery. The data suggest that spindles in NREM sleep may be involved in
      sleep maintenance, while spindles heralding the transition to REM sleep may be
      related to mechanisms of REM sleep initiation.

PMID- 15493553
TI  - The dream between neuroscience and psychoanalysis.
AB  - The dream is tackled sometimes from the neurobiological viewpoint, sometimes from
      the neuropsychological angle, or from the positions of experimental and
      psychoanalytical psychology. Interest in dreams started with psychoanalysis in
      1900, and 53 years later the discovery of REM sleep by Aserinski and Kleitman,
      and subsequent psychophysiological findings took the dream into the realm of
      biology. The dichotomous model of REM and non-REM sleep is described, as a basis
      for thought-like activity (non-REM sleep) and dreaming (REM sleep). This led to
      Hobson and McCarley's theory of activation-synthesis, suggesting that the mind
      while dreaming is simply the brain self-activated in REM sleep.
      Psychophysiological research has shown that people dream in all phases of sleep,
      from falling asleep to waking, but that the characteristics of the dreams may
      differ in the different phases. Bio-imaging studies indicate that during REM
      sleep there is activation of the pons, the amygdala bilaterally, and the anterior
      cingulate cortex, and disactivation of the posterior cingulate cortex and the
      prefrontal cortex. The images suggest there is a neuroanatomical frame within
      which dreams can be generated and then forgotten. Psychoanalysis studies the
      dream from a completely different angle. Freud believed it was the expression of
      hallucinatory satisfaction of repressed desires. Today it is interpreted as the
      expression of a representation of the transference in the hic et nunc of the
      session. At the same time it also has symbol-generating functions which provide
      an outlet by which affective experiences and fantasies and defences stored as
      parts of an unrepressed unconscious in the implicit memory can be represented in
      pictorial terms, then thought and rendered verbally. From the psychoanalytical
      point of view, the dream transcends neurobiological knowledge, and looks like a
      process of internal activation that is only apparently chaotic, but is actually
      rich in meanings, arising from the person's affective and emotional history.

PMID- 15493554
TI  - Genes for prostaglandin d synthase and receptor as well as adenosine A2A receptor
      are involved in the homeostatic regulation of nrem sleep.
AB  - (1) Prostaglandin D2 is essential for the maintenance of the sleep state. (2) The
      adenosine and A2A receptor system is a link between the humoral and neural
      mechanisms of sleep-wake regulation. (3) Prostaglandin D2 plays a crucial role in
      the homeostatic regulation of NREM sleep. Finally, it may not be too far-fetched
      to say that prostaglandin D2 was most likely the endogenous sleep substance
      described by Pieron and Ishimori about 100 years ago, and possibly the sleep
      inducing factor reported by Professor Jouvet and coworkers some twenty years ago.

PMID- 15493555
TI  - Uncoupling proteins and sleep deprivation.
AB  - In both humans and animals sleep deprivation (SD) produces an increase in food
      intake and in energy expenditure (EE). The increase in EE is a core element of
      the SD syndrome and, in rats, is negatively correlated with survival rate.
      However, the mechanisms involved are not understood. A large component of resting
      EE is accounted for by the mitochondrial proton leak, which is mediated by
      uncoupling proteins (UCPs). We measured UCP2, UCP3, and UCP5 mRNA levels in rats
      during the spontaneous sleep/waking cycle and after short (8 hours) and long (7
      days) SD. During spontaneous sleep and waking there was no change in the level of
      mitochondrial uncoupling as measured by UCPs expression, either in the brain or
      in peripheral tissues. During SD, by contrast, UCP3 expression in skeletal muscle
      was elevated, but the increase was similar, compared to sleep, after both short
      term and long-term SD. UCP2 expression, on the other hand, was strongly increased
      in the liver and skeletal muscle of long-term sleep deprived animals and much
      less so, or not at all, in yoked controls or in rats that lost only 8 hours of
      sleep. Since the skeletal muscle is the largest tissue in the body, an elevated
      muscular expression of UCP2 is likely to affect the overall resting EE and may
      thus contribute to its increase after SD.

PMID- 15493556
TI  - Cortical and pontine variations occurring in the voltammetric no signal
      throughout the sleep-wake cycle in the rat.
AB  - Voltammetric measurements of nitric oxide (NO) were performed either in the
      frontal cortex (Cx) or in the nucleus raphe dorsalis (nRD) of rats equipped for
      polygraphic recordings. In the frontal cortex, the 650 mV signal related to NO
      exhibited its highest height during the waking state (W) and decreased slightly
      during slow-wave sleep (SWS) and even more during paradoxical sleep (PS). In the
      nRD, opposite variations were observed, i.e. the signal tended towards an
      increase during SWS and raised more consistently during PS versus W. Recordings
      performed either in the Cx or the nRD, throughout the light (12-h) and dark (12
      h) periods, exhibited opposite nycthemeral changes, i.e. the signal height was
      higher in the Cx and lower in the nRD during the dark period and conversely for
      the light one. Paracrine and synaptic mechanisms taking place within the pons
      and, at least partly, also reflected in the Cx need to be further investigated.

PMID- 15493557
TI  - Relationship between sleep and eye state in Cetaceans and Pinnipeds.
AB  - We recorded EEG from both hemispheres and documented the state of the two eyes in
      two species of Cetaceans (one beluga and one bottlenose dolphin) and one species
      of Pinnipeds (two northern fur seals). In the dolphin and beluga we found that
      episodes of unihemispheric slow wave sleep (USWS) were associated with asymmetry
      in eye state. During USWS and asymmetrical SWS the eye contralateral to the
      sleeping hemisphere was mostly closed or in an intermediate state while the eye
      contralateral to the waking hemisphere was more often open or in an intermediate
      state. Bilateral eye opening indicated waking in about 80% cases and unilateral
      eye closure indicated USWS with an accuracy of about 75%. Bilateral eye closure
      was rare (< 2% of the observation time) and was not necessarily associated with
      high amplitude SWS. In fur seals, episodes of one eye briefly opening usually
      occurred in the beginning of sleep episodes and lasted several minutes. Those
      episodes were frequently associated with lower amplitude EEG slow waves in the
      contralateral brain hemisphere. During most of their sleep on land, fur seals had
      both eyes tightly closed. No EEG asymmetry was recorded at this time. Although
      eye state and EEG stage are correlated in the bottlenose dolphin, beluga and fur
      seals, short episodes of EEG synchrony (less then 1 min) occur contralateral to
      an open eye and waking (a more activated EEG) activity can be present
      contralateral to a closed eye. The available data suggest that two functions of
      USWS/EEG asymmetry during SWS in Cetaceans and fur seals are multisensory control
      of the environment and maintenance of motion and postures of sleep. The adaptive
      advantages of USWS throughout the evolution of Cetaceans and Pinnipeds from
      terrestrial mammals to present forms could include 1) the avoidance of predators
      and maintenance of contact with other animals of the same species; 2) continuance
      of regular breathing; 3) and effective thermoregulation in the water environment.

PMID- 15493558
TI  - [The ontogeny and physiology confirms the dual nature of sleep states].
AB  - In the Jouvet's laboratory, as early as 1960 the study of the ontogenesis of
      paradoxical sleep (PS) named "sleep 'with jerks" began in the kitten and led to
      the first publication in 1961. Then, several species were studied, lamb, rat,
      human neonates, etc. These works showed that at birth sleep with jerks was
      preponderant in altricial (immature) species (cat, rat) and the first to appear
      during the second half of gestation in precocious species (guinea pig). For
      Jouvet, sleep with jerks is a immature form of PS. Why PS is so important at
      birth? The maturation of the central nervous system, based on the myelinization,
      starts in the spinal cord then forwards to the brainstem and forebrain. So, PS
      mechanisms located in the brainstem are the first to mature and the only one to
      function. Then the slow wave sleep (SWS) and waking structures become mature.
      Phylogenetic studies showed that in mammals and birds PS was present even in
      marsupials and monotremes. Until now only the one exception is the dolphin with a
      voluntary breathing. To sleep and breath, dolphin has developed an unilateral
      sleep without classical PS. In other animals, reptiles, amphibians, fishes, PS
      was not observed with the parameters used in mammals. The study at birth (not yet
      done) of reptiles would allow perhaps the observation of a temporary PS. Based on
      these findings, a schematic model of the sleep regulation can be elaborated.
      Haeckel's aphorism "Ontogeny recapitulates phylogeny" seems true for PS which
      appears in birds and mammals i.e. at the end of evolution as it appears at the
      end of gestation when PS cerebral structures are present and mature.

PMID- 15493559
TI  - Significance of lower uterine segment involvement in women with stage I
      endometrial adenocarcinoma.
AB  - OBJECTIVE: To determine whether lower uterine segment involvement (LUSI)
      correlates with recurrence and survival in women with stage I endometrial
      adenocarcinoma who do not receive postoperative radiotherapy on the basis of this
      histologic criterion. STUDY DESIGN: Eighty patients with endometrial
      adenocarcinoma stage I who underwent surgery between 1989 and 2002 were divided
      into 2 groups according to the presence of LUSI. Group 1 consisted of 25 patients
      with LUSI; group 2 consisted of 55 patients without LUSI. The 2 groups were
      compared with regard to prognostic factors and outcome measures. RESULTS: There
      were no statistically significant differences between the 2 groups with regard to
      the following parameters: age and proportion of patients who underwent complete
      surgical staging and postoperative adjuvant radiotherapy. Pathologic parameters
      of the 2 groups, such as histologic type, grade and deep myometrial invasion,
      were comparable. A greater proportion of patients with LUSI had capillary space
      like involvement. The patients were followed for a median of 48 months (range, 11
      168) from the date of surgery. The overall 5-year recurrence-free survival,
      disease-specific survival and overall survival rates were 91% (SE .04), 94% (SE
      .03) and 77% (SE .06), respectively. There was no significant difference between
      the two groups with regards to these measures (P < .05). CONCLUSION: In patients
      with state I endometrial cancer, the presence of lower uterine segment
      involvement does not correlate with their outcome.

PMID- 15493560
TI  - Trends in twinning rates in metropolitan Atlanta before and after folic acid
      fortification.
AB  - OBJECTIVE: To examine whether trends in rates of twinning in metropolitan Atlanta
      increased after folic acid fortification. STUDY DESIGN: Live births to residents
      of 5 metropolitan Atlanta counties during the period 1990-2001 were identified
      from the state of Georgia's vital records. Rates of twinning and rate ratios were
      computed for the periods before and after fortification with folic acid. RESULTS:
      Of the 510,000 singleton and twin births in metropolitan Atlanta during the study
      period, 7168 (1.43%) represented twin pregnancies. Overall, the rate of twinning
      increased 18% (P < .001)from the prefortification to postfortification period. As
      compared with the rate of twinning during the prefortification period, that
      during the postfortification period increased by 23% (OR 1.23, 95% CI 1.7, 1.28)
      among women over 30 years but showed no increase among women <30 years of age (OR
      1.02, CI 0.94, 1.10). Among women >30, there was an increasing rate of twinning
      throughout the prefortification period (4.9%). There was no upward trend in
      twinning rates among women younger than 30 years prior to fortification.
      CONCLUSION: Increasing trends of twinning were observed only in women older than
      30 years, but these trends began prior to folic acid fortification and reached a
      plateau in recent years. Further elucidation of the possible relationship between
      folic acid and twinning will need to account for the use of fertility treatments
      by older women.

PMID- 15493561
TI  - Relationship of high pretreatment folic acid level and failure of methotrexate in
      ectopic pregnancy: a pilot study.
AB  - OBJECTIVE: To test the hypothesis that high (> or =20.7 ng/mL) pretreatment serum
      folic acid level increases the failure of single-dose methotrexate for ectopic
      pregnancy. STUDY DESIGN: Twenty patients with ectopic pregnancy and measured
      pretreatment folic acid levels were divided into 2 groups based on pretreatment
      serum folic acid level (< or > or =20.7 ng/mL). All patients were candidates for
      single-dose methotrexate treatment. Variables analyzed in the 2 groups were
      pretreatment folic acid level, initial P-human chorionic gonadotropin (hCG)
      level, size of the ectopic mass, presence of fetal heart tones and clinical
      outcomes. RESULTS: Eleven patients had serum folic acid levels < and 9 > or =20.7
      ng/mL. The mean (+/- SD) folic acid level was 13.4 ng/mL (+/- 3.2) in the group
      with folic acid levels <20.7 ng/mL, significantly lower than in the group with
      folic acid levels >20.7 ng/mL (p <0.001). The 2 groups were similar in initial
      hCG level, size of the ectopic mass and presence of fetal heart tones. The
      failure rate was significantly higher in the group with pretreatment serum folic
      acid levels > or = 20.7 ng/mL as compared to the group below (n = 4, 44%, vs. n =
      0, 0%; p = 0.02). CONCLUSION: High pretreatment folic acid levels increase the
      risk of treatment failure with single-dose methotrexate.

PMID- 15493562
TI  - Laparoscopic pomeroy tubal ligation: a comparison with tubal cauterization in a
      teaching hospital.
AB  - OBJECTIVE: To compare laparoscopic Pomeroy tubal ligation to standard bipolar
      tubal cauterization for the outcome measures of failure rate, complication rate
      and procedure duration, with an analysis of the effect of resident experience on
      procedure duration. STUDY DESIGN: Retrospective study of patients presenting for
      interval sterilization between August 1998 and June 2000. RESULTS: The
      characteristics of the laparoscopic Pomeroy (n = 99) and bipolar cautery (n = 62)
      patients were comparable. The mean procedure duration was 40.8 +/- 14.6 minutes
      for laparoscopic Pomeroy and 39.6 +/- 18.8 minutes for bipolar cautery (p <
      0.68). Multiple regression analysis revealed that procedure duration was a
      function of both months in residency (R2 = .098, p < 0.007) and number of
      laparoscopic Pomeroy procedures performed (R2 = .082, p < 0.01). One complication
      occurred with each procedure (p < 0.576). Two sterilization failures occurred
      after bipolar cautery and 1 after laparoscopic Pomeroy (p < 0.33). The
      laparoscopic Pomeroy failure occurred in the shortest tubal segment obtained, 0.7
      cm, versus the average segment length, 2.07 +/- .79 cm. CONCLUSION: Laparoscopic
      Pomeroy did not differ from bipolar cautery for the outcome measures studied.
      Both time in residency and procedure-specific experience affect the duration of
      laparoscopic Pomeroy. A tubal segment length of 1 cm should be removed to limit
      sterilization failures.

PMID- 15493563
TI  - Risks in triplet pregnancy: advanced maternal age, premature rupture of membranes
      and risk estimates of mortality.
AB  - OBJECTIVE: To investigate the impact of older maternal age on the risk of
      mortality associated with premature rupture of membranes (PROM) among triplets.
      STUDY DESIGN: A retrospective, cohort study was performed on triplet deliveries
      in the United States that occurred in the period perinatal and 1995-1998. The
      study group comprised mothers aged > or =40 years (older mothers), who were
      compared to mothers aged 30-39 (mature mothers), 20-29 (younger mothers) and
      mothers <20 (teenagers). We computed risks of mortality associated with PROM
      within each maternal age category using generalized estimating equations to take
      into account both intracluster and intercluster sources of variation. RESULTS:
      The risk of stillbirth and of neonatal and perinatal mortality related to PROM
      was highest among teenagers. In all circumstances, the risk of both intrauterine
      and extrauterine death resulting from PROM diminished progressively with
      increasing maternal age until age 40 and beyond, at which point the risk rose
      once more and produced a U shape. PROM triplets of older mothers had apparently
      higher mortality indices than did those of younger and mature mothers, although
      the risk difference did not show statistical significance for any of the
      mortality indices. Similarly, the proportion of preventable deaths if PROM could
      be averted demonstrated a U-shape, consistent with that of risk estimates.
      CONCLUSION: Premature rupture of membranes was associated with an increase risk
      of perinatal and infant mortality among triplets. Although older mothers
      demonstrated higher risk levels for all mortality indices in comparison to
      younger and mature mothers, our findings did not reach statistical significance.

PMID- 15493564
TI  - Fertilization failure from a sperm chromatin defect in couples with unexplained
      infertility.
AB  - OBJECTIVE: To investigate the relationship between unexplained infertility and
      fertilization failure from nucleoprotein defects in ejaculated human sperm and to
      study the usefulness of sperm chromatin assays, using AO fluorescence dye, to
      evaluate patients with unexplained infertility before treatment. STUDY DESIGN:
      From January 1999 to January 2000, 513 infertile couples had the clinical causes
      of their infertility assessed. During the next investigative period (February
      2000-February 2001), 137 cases of unexplained infertility (n = 80) were chosen
      for this study, as were cases of tubal factor infertility (n = 57) as controls.
      The status of nuclear chromatin in ejaculated sperm was examined using acridine
      orange staining, followed by a conventional in vitro fertilization procedure.
      RESULTS: The number of patients with immature ejaculated sperm was 16 of 30
      (53.3%) unexplained infertility cases involving fertilization failure, 8 of 50
      (16.0%) unexplained infertility cases without fertilization failure and 5 of 57
      (8.8%) tubal factor infertility cases. A significant difference was observed
      between unexplained infertility cases with fertilization failure and the other
      groups (P < .0001). CONCLUSION: These results suggest that the nuclear immaturity
      of ejaculated human sperm may be 1 of the primary factors underlying unexplained
      infertility.

PMID- 15493565
TI  - Efficacy of recombinant human follicle-stimulating hormone in improving oocyte
      quality in assisted reproductive techniques.
AB  - OBJECTIVE: To estimate the efficacy of recombinant human follicle-stimulating
      hormone (rFSH) versus highly purified urinary human FSH (uFSH) in women
      undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization
      and embryo transfer (IVF-ET). STUDY DESIGN: This prospective, randomized, quality
      of retrieved double-blind study compared uFSH with rFSH in IVF-ET rFSh cycles. A
      total of 254 cycles from 241 patients who attended the infertility clinic at
      Samsung Cheil Hospital from January to August 2001 were included in the study.
      With pituitary desensitization using gonadotropin-releasing hormone agonist and a
      short protocol, rFSH was administered in 131 cycles; uFSH was administered in 123
      cycles. We analyzed ovarian response, oocyte quality, fertilization rate, embryo
      quality, pregnancy rate and live birth rate in the uFSH and rFSH groups. RESULTS:
      Total FSH dosage (1322.3 +/- 526.2 vs. 2124.4 +/- 881.9 i.u.) and dosage per
      retrieved oocyte (90.6 +/- 36.0 vs. 138.0 +/- 57.2 i.u.) were significantly lower
      in the rFSH group than those in the uFSH group (P < .001). The proportion of good
      quality oocytes (grade 1 and 2) was higher in the rFSH group (68.2% vs. 64.8%, P
      = .024). Moreover, the proportion of atretic oocytes (grade 5) was lower in the
      rFSH group (7.5% vs. 10.3%, P = .002). The fertilization rate, quality of
      transferred embryos, clinical pregnancy rate and live birth rate were not
      significantly differ between the 2 groups. CONCLUSION: In women undergoing COH,
      rFSH revealed more efficient ovarian response and better quality of oocytes than
      did uFSH.

PMID- 15493566
TI  - Continuous, low-level, topical heat wrap therapy as compared to acetaminophen for
      primary dysmenorrhea.
AB  - OBJECTIVE: To determine if pain relief provided by a wearable heat wrap
      (continuous, low-level, topical heat therapy) is superior to oral acetaminophen
      for primary dysmenorrhea. STUDY DESIGN: A randomized, active-controlled,
      multisite, single-blind (investigator), parallel-design study compared an
      abdominal wrap to an oral medication (acetaminophen, 1000 mg) over I day. Pain
      relief (0-5) and abdominal muscle tightness/cramping (0-100) were recorded at 12
      time points. At 24 and 48 hours, menstrual symptom-based quality of life was
      assessed. RESULTS: Three hundred sixty-seven subjects entered the study, with 344
      subjects evaluable. The heat wrap was superior to acetaminophen for pain relief
      over an 8-hour period (means of 2.48 and 2.17, p = 0.015) and at t hours 3, 4, 5
      and 6 (p < or = 0.05). Tightness/cramping was less for the heat wrap versus
      acetaminophen over 8 hours (means of 40.4 and 44.5, p = 0.04) and at hours 4, 5
      and 6 (p < or = 0.05). There was significantly decreased fatigue, fewer mood
      swings and less lower abdominal cramping (p < or = 0.05) with heat therapy.
      CONCLUSION: Continuous, low-level, topical heat therapy was superior to
      acetaminophen for the treatment of dysmenorrhea.

PMID- 15493568
TI  - Adenocarcinoma of the appendix in pregnancy: a case report.
AB  - BACKGROUND: Perforation of an adenocarcinoma of the appendix in a pregnant woman
      is rare and may present as a pelvic mass and acute appendicitis. CASE: A 30-year
      old woman, gravida 3, para 2-0-0-2, presented at 26 weeks' gestation with an
      acute abdomen, right-sided pelvic mass and uterine contractions. Tocolysis and
      prompt surgical exploration revealed a perforated appendix. The patient underwent
      a right hemicolectomy with primary anastomosis, her postoperative course was
      benign, and she delivered a viable infant at term vaginally. Pathology revealed a
      perforated adenocarcinoma of the appendix. The patient was free of disease at 36
      months. CONCLUSION: Adenocarcinoma of the appendix in pregnancy is rare, may
      present as an acute abdomen with a mass and is managed with right hemicolectomy.

PMID- 15493567
TI  - The androgenic profile of women with non-insulin-dependent diabetes mellitus.
AB  - OBJECTIVE: To evaluate the androgenic profile of women with non-insulin-dependent
      diabetes mellitus. STUDY DESIGN: This case-control study evaluated the clinical,
      hormonal and ultrasonographic characteristics of women of reproductive age with
      non-insulin-dependent diabetes mellitus and compared them with those of age- and
      weight-matched controls. Radioimmunoassays were used for total testosterone,
      estradiol, dehydroepiandrosterone sulfate (DHEAS) and androstenedione. Sex
      hormone-binding globulin (SHBG), luteinizing hormone (LH) and follicle
      stimulating hormone (FSH) were analyzed by fluoroimmunoassays. Ovarian appearance
      and volume were assessed by transvaginal or transabdominal ultrasonography.
      RESULTS: The prevalence of polycystic ovary syndrome was higher in diabetic
      patients than in the general population as reported earlier. Hirsutism was also
      more prevalent in diabetic patients (p < 0.05). The serum levels of FSH, LH,
      estradiol, total testosterone, androstenedione and DHEAS were significantly
      higher in diabetic patients than in the control group (p < 0.05). In contrast,
      the levels of SHBG were lower in diabetic patients (p < 0.05). The rates of
      ultrasonographically apparent polycystic ovaries and greater ovarian volumes were
      also higher in diabetic patients (p < 0.05). CONCLUSION: Women with non-insulin
      dependent diabetes mellitus seem to have biochemical and clinical
      hyperandrogenism when compared with nondiabetic controls.

PMID- 15493569
TI  - Recanalization of a fallopian tube after detorsion of twisted adnexa: report of a
      case with follow-up by repeat hysterosalpingography.
AB  - BACKGROUND: Detorsion and cystectomy of twisted adnexa have been performed in
      young women. However, identification was incomplete, and the function of the
      affected tube was not investigated. CASE: A 23-year-old, nulligravid woman with
      an acute abdomen was diagnosed with adnexal torsion. An emergency laparotomy
      revealed that both ovaries were 12x9x9 cm. the right adnexa were twisted and
      bluish black. Detorsion of the twisted lesion and ipsilateral fallopian tube was
      performed, with subsequent cystectomy of both lesions. Hysterosalpingography on
      the 14th postoperative day showed right tubal obstruction; 6 months
      postoperatively, repeat hysterosalpingography revealed patency of the right tube.
      CONCLUSION: At least several months may be required for functional recovery of an
      untwisted tube. For that reason, postoperative repeat hysterosalpingography is a
      useful method for follow-up of function in an untwisted tube.

PMID- 15493570
TI  - Primary ovarian pregnancy after postpartum bilateral tubal ligation: a case
      report.
AB  - BACKGROUND: Primary ovarian pregnancy constitutes <1% of ectopic gestations.
      Likewise, bilateral tubal ligation failure is uncommon, occurring in
      approximately 1% of tubal sterilization procedures. Should pregnancy occur after
      bilateral tubal ligation, of every 3 such pregnancies, 1 will be an ectopic. The
      incidence of ovarian pregnancy after tubal ligation has not been reported, but
      must be extremely rare. CASE: A 30-year-old, breast-feeding, white woman 6 months
      postpartum, with bilateral tubal ligation after delivery, developed acute right
      lower quadrant pain while excercising. Evaluation in the emergency room revealed
      rebound tenderness in the lower right abdomen, a positive beta-hCG level and
      ultrasound findings suspicious for a right ectopic pregnancy. Exploratory
      laparotomy revealed hemoperitoneum, previously ligated but otherwise-normal
      appearing fallopian tubes, and a ruptured and bleeding right ovary. The pelvis
      was otherwise normal. Histology of the right ovarian wedge resection showed
      chorionic villi consistent with ovarian pregnancy. Both fallopian tubes were
      religated, and a review of the original tubal ligation histology confirmed tubal
      lumen in both segments. CONCLUSION: While ectopic pregnancy is a known but rare
      risk of failed tubal sterilization, pregnancy involving the fallopian tube is
      usually reported after tubal ligation failure. The rarely seen primary ovarian
      pregnancy is usually associated with intrauterine contraceptive devices or occurs
      in patients with pelvic inflammatory disease. Ovarian pregnancies are associated
      with massive hemoperitoneum in women unaware that they are pregnant.

PMID- 15493571
TI  - Ovarian abscess from Salmonella: a case report.
AB  - BACKGROUND: An ovarian site of Salmonella bacteremia is rare. The contents of a
      teratoma may hide the organisms easily. Clinicians should be alert to this
      possibility when the patient had a teratoma with Salmonella infection. CASE: A 19
      year-old woman presented with a missed menstrual period. An adnexal mass was
      found during a routine gynecologic examination. The patient had had
      gastroenteritis 2 months earlier but did not complain of a gastrointestinal
      problem at presentation. Exploratory laparotomy was performed for a suspected
      ovarian tumor. An infective teratoma was considered, but the infection source was
      unknown until the culture report showed a Salmonella infection. CONCLUSION:
      Salmonella infection is a self-limiting, febrile disease and is unlikely to
      involve organs other than the gut. A nontyphoid ovarian abscess became a rare
      late complication of acute gastroenteritis. Clinicians should pay special
      attention to the differential diagnosis of ovarian tumor in patients with a
      history of Salmonella infection, especially those with such ovarian lesions as
      endometrioma or teratoma and with recent abdominal pain, as noted in this case.

PMID- 15493572
TI  - Agnogenic myeloid metaplasia in an ovarian steroid cell tumor with virilization:
      a case report.
AB  - BACKGROUND: Extramedullary hematopoiesis in patients without hematologic
      disorders is very rare and has apparently never been described previously in
      association with an ovarian steroid cell tumor. CASE: An 18-year-old woman was
      admitted to our clinic due to primary amenorrhea. the On examination she had
      significant facial hirsutism, clitoromegaly and and Adam's apple. The serum level
      of testosterone was elevated. A 7-cm, right ovarian mass was enucleated during
      laparotomy. Histology revealed a steroid cell tumor with foci of myeloid
      metaplasia; bony trabecula formation was present. There was no evidence of
      hematologic or systemic disease. The hormone values became normal 1 month
      postoperatively. CONCLUSION: This report describes a patient with agnogenic
      myeloid metaplasia in an ovarian steroid cell tumor with virilization; this
      association was not previously reported.

PMID- 15493573
TI  - Thermal balloon endometrial ablation.

PMID- 15493574
TI  - Heterogeneous populations of bone marrow stem cells--are we spotting on the same
      cells from the different angles?
AB  - Accumulated evidence suggests that in addition to hematopoietic stem cells (HSC),
      bone marrow (BM) also harbors endothelial stem cells (ESC), mesenchymal stem
      cells (MSC), multipotential adult progenitor cells (MAPC), pluripotent stem cells
      (PCS) as well as tissue committed stem cells (TCSC) recently identified by us. In
      this review we discuss the similarities and differences between these cell
      populations. Furthermore, we will present the hypothesis that all of these
      versatile BM derived stem cells are in fact different subpopulations of TCSC.
      These cells accumulate in bone marrow during ontogenesis and being a mobile
      population of cells are released from BM into peripheral blood after tissue
      injury to regenerate damaged organs. Furthermore, since BM is a "hideout" for
      TCSC, their presence in preparations of bone marrow derived mononuclear cells
      should be considered before experimental evidence is interpreted simply as trans
      differentiation or plasticity of HSC. Finally, our observation that the number of
      TCSC accumulate in the bone marrow of young animals and their numbers decrease
      during senescence provides a new insight into aging and may explain why the
      regeneration processes becomes less effective in older individuals.

PMID- 15493575
TI  - Peritonitis-induced antitumor activity of peritoneal macrophages from uremic
      patients.
AB  - The macrophages belong to the effector cells of both nonspecific and specific
      immune response. These cells generally express little cytotoxicity unless
      activated. The present work was intended to determine if peritoneal macrophages
      collected from patients on Continuous Ambulatory Peritoneal Dialysis (CAPD)
      during episodes of peritonitis were active against human tumor cell lines without
      further in vitro stimulation. We also compared macrophage antitumor potential
      with effectiveness of drugs used in cancer therapy (taxol and suramin).
      Conditioned medium (CM) of macrophages collected during inflammation-free periods
      did not exhibit cytostatic and cytotoxic activity against both tumor (A549 and
      HTB44) and non-transformed (BEAS-2B and CRL2190) cells. Exposure of tumor cells
      to CM of macrophages harvested during peritonitis resulted in significant
      suppression of proliferation, impairment of viability and induction of apoptosis,
      in contrast to non-transformed cells, which remained unaffected. The efficacy of
      CM of inflammatory macrophages as an antitumor agent appeared to be comparable to
      cytostatic and cytotoxic potency of taxol and suramin or, in the case of HTB44
      cells, even higher. The results obtained suggest that activated human macrophages
      might represent a useful tool for cancer immunotherapy.

PMID- 15493576
TI  - Diurnal rhythms of pinealocyte ultrastructure, pineal serotonin content and
      plasma melatonin level in the domestic pig.
AB  - The study was conducted to investigate diurnal changes in pinealocyte
      ultrastructure, pineal serotonin content and plasma melatonin concentration in
      the domestic pig. The immature pigs (n=24) were kept under a cycle of 12 h light
      : 12 h dark, with a photophase between 0800 and 2000. During the photophase the
      animals were exposed to direct sunlight. After four weeks the gilts were
      slaughtered at 0900, 1400, 2100 and 0200. The pineals were removed and divided
      into two parts - one for quantitative ultrastructural study (by a point count
      method) and one for serotonin assay. Simultaneously, blood samples were taken for
      melatonin assay. The relative volume of mitochondria in pinealocyte perikarya was
      significantly higher at 1400 than at 0200 and 0900 as well as at 2100 than at
      0200. The relative volume of Golgi apparatus was higher at 0900 and 1400 than at
      0200. The relative volume of dense bodies of the MBB-1 type in pinealocyte
      perikarya was significantly lower at 1400 and 2100 than at 0900. In contrast, the
      relative volume of MBB-2 was higher at 1400 than at 0900 and 0200. The numerical
      density of DCV in perikarya was significantly higher at 0200 than at 1400. No
      significant differences were found in rough endoplasmic reticulum, lysosomes and
      multivesicular bodies. The pineal serotonin content showed a prominent rhythm
      with the maximum at 1400. The plasma melatonin concentration was significantly
      higher at 0200 than at 0900, 1400 and 2100. The obtained results demonstrate that
      both pinealocyte ultrastructure and pineal biochemistry in the pig undergo
      significant changes in the course of the diurnal rhythm.

PMID- 15493577
TI  - Assessment of proliferative activity of thyroid Hurthle cell tumors using PCNA,
      Ki-67 and AgNOR methods.
AB  - We have undertaken an attempt to compare the application efficacy of the
      proliferative activity markers in differential diagnosis of thyroid Hurthle cell
      tumors (HCT) using the PCNA and Ki-67 labeling and AgNOR visualisation
      techniques. The present work is a retrospective analysis of 78 Hurthle cell
      tumors: 20 Hurthle cell carcinomas (HCC), 32 Hurthle cell adenomas (HCA) and 26
      hyperplastic nodules with Hurthle cell metaplasia (HCM). Five microm sections
      were stained according to AgNOR technique and labeled with antibodies against
      PCNA and Ki-67. AgNOR dot count in the nucleus and proliferative index (PI -
      percentage of cells expressing PCNA and Ki-67) in randomly chosen nuclei (100 in
      case of AgNOR and over 1000 in case of PI) were evaluated in each slide. The mean
      values of AgNOR dot count, PI-PCNA and PI-Ki-67 in HCC, HCA and HCM were
      respectively: 5.1, 61.3 and 54.9; 3.4, 42.4 and 38.6 and 2.5, 39.3 and 34.3.
      Statistically significant difference was found in all the proliferative activity
      markers between malignant and benign tumors: HCC:HCA (p<0.01) and HCC:HCM
      (p<0.001). There was no statistically significant difference between HCA and HCM.

PMID- 15493578
TI  - Assessment of prognostic significance of cytoplasmic survivin expression in
      advanced oesophageal cancer.
AB  - Survivin is a member of the family of proteins, which inhibit apoptosis
      (inhibitor of apoptosis proteins - IAP). Expression of survivin was found in
      colorectal cancer, neuroblastoma, bladder cancer, non-small cell lung cancer, and
      breast cancer. There is some recent data indicating the correlation of poor
      prognosis and worse response to chemotherapy in patients with oesophageal
      squamous cell carcinoma (OSCC) expressing survivin. The aim of the present study
      was to assess survivin expression in cancerous tissue of patients with advanced
      OSCC and to test the potential correlation between survivin expression and
      clinicopathological data. Forty two patients (mean age 58.36+/-8.97 yrs), who
      were oesophagectomised due to squamous cell carcinoma of the thoracic oesophagus
      between 1998 and 2000, were retrospectively analysed. Cytoplasmic survivin
      expression, examined immunohistochemically, was found in 35 (83.33%) cases. No
      statistically significant correlation between survivin expression in the tumour
      and patients' gender, TNM stage, or vascular involvement was noted. The mean
      survival of patients with cytoplasmic survivin expression (17.81+/-5.51 months)
      was not statistically different to those with negative survivin staining (16+/
      6.28 months) as assessed by Mantel-Cox test (p=0.49). Univariate regression
      analysis revealed UICC staging as the only predictor of survival in the analysed
      group (p<0.05). These results indicate that the cytoplasmic survivin expression
      does not seem to be the prognostic factor in advanced cases of OSCC.

PMID- 15493579
TI  - K-RAS point mutation, and amplification of C-MYC and C-ERBB2 in colon
      adenocarcinoma.
AB  - The routine multidisciplinary management of colon cancer is based mainly on tumor
      staging, histology, grading and vascular invasion. In this approach, important
      individual information derived from molecular characteristics of the tumor may be
      missed, especially since significant heterogeneity of molecular aberrations in
      cancer cells has been observed, and recognition of every of relationships between
      them may be of value. K-RAS, C-MYC and C-ERBB2 are protooncogenes taking part in
      carcinogenesis and tumor progression in the colon. They influence cell
      proliferation, differentiation and survival. K-RAS point mutation, as well as
      amplification of C-MYC and C-ERBB2 were searched in 84 primary colon
      adenocarcinomas resected with curative intent. Multiplex polymerase-chain
      reaction and restriction fragment length polymorphism were performed to assess
      codon 12 K-RAS point mutation. Amplification of C-MYC and C-ERBB2 genes was
      evaluated by densitometry after agarose gel separation of the respective
      multiplex PCR products. No relation was found among mutated and/or amplified
      genes, and between searched molecular aberrations and pathoclinical features. In
      multivariate analysis, nodal status appeared to be the only independent
      prognostic indicator. In colon adenocarcinoma, codon 12 K-RAS point mutation and
      amplification of C-MYC and C-ERBB2 seem to occur independently in the process of
      tumor progression. Amplification of C-ERBB2 tends to associate with more advanced
      stage of disease. Concomitant occurrence of codon 12 K-RAS mutation, C-MYC and C
      ERBB2 amplification was of no prognostic value in respect to survival.

PMID- 15493580
TI  - Characteristics of myosin profile in human vastus lateralis muscle in relation to
      training background.
AB  - 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 were
      investigated and classified into three groups according to their physical
      activity and sport discipline: untrained students (group A), national and sub
      national level endurance athletes (group B, 7.8+/-2.9 years of specialised
      training) and sprint-power athletes (group C, 12.8+/-8.7 years of specialised
      training). Muscle biopsies of vastus lateralis were analysed histochemically for
      mATPase and SDH activities, immunohistochemically for fast and slow myosin, and
      electrophoretically followed by Western immunoblotting for myosin heavy chain
      (MyHC) composition. Significant differences (P<0.05) regarding composition of
      muscle fibre types and myosin heavy chains were found only between groups A
      (41.7+/-1.6% of MyHCI, 40.8+/-4.0% of MyHCIIA and 17.5+/-4.0% of MyHCIIX) and B
      (64.3+/-0.8% of MyHCI, 34.0+/-1.4% of MyHCIIA and 1.7+/-1.4% of MyHCIIX) and
      groups A and C (59.6+/-1.6% of MyHCI, 37.2+/-1.3% of MyHCIIA and 3.2+/-1.3% of
      MyHCIIX). Unexpectedly, 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. Furthermore, the
      relative amount of the fastest MyHCIIX isoform in vastus lateralis muscle was
      significantly lower in the athletes from group C than in students (group A). We
      conclude that the myosin profile in the athletes belonging to group C was
      unfavourable for their sport disciplines. This could be the reason why those
      athletes did not reach international level despite of several years of training.

PMID- 15493581
TI  - The localization of Fos B, a member of transcription factor AP-1 family, in rat
      odontoblasts and pulpal undifferentiated ectomesenchymal cells.
AB  - It has been proposed that cellular proliferation and differentiation are
      accomplished by AP-1 components but different components can be responsible for
      different functions. The aim of this study was to compare the localization of Fos
      B, which is a component of AP-1, in postmitotic differentiated and
      undifferentiated cells via Fos B immunoreactivity. For this purpose, maxillary
      incisor teeth from 10 Wistar rats were obtained and Fos-B was investigated
      immunohistochemically in formalin-fixed, paraffin-embedded tooth sections
      containing odontoblasts, which are postmitotic differentiated cells, and pulpal
      undifferentiated ectomesenchymal cells. No significant differences in percentage
      of Fos B-positive cells were observed between the two cell types (p>0.05). These
      findings suggest that Fos B, a component of AP-1 family, seems to have a
      negligible effect on differentiation and proliferation in odontoblasts and pulpal
      undifferentiated ectomesenchymal cells.

PMID- 15493582
TI  - Two methods for the quantitative analysis of surface antigen expression in acute
      myeloid leukemia (AML).
AB  - The expression of lineage molecules (CD13 and CD33), c-Kit receptor (CD117),
      CD34, HLA-DR and adhesion molecule CD49d was assessed in acute myeloid leukemia
      (AML) blast cells from 32 cases, using direct and indirect quantitative
      cytometric analysis. High correlation (r=0.8) was found between antigen
      expression intensity values calculated by direct analysis method (ABC) and by
      indirect analysis method (RFI). Moreover, the differences in expression intensity
      of CD13, CD117 and CD34 antigens were found between leukemic and normal
      myeloblasts. This may be helpful in identification of leukemic cells in the
      diagnostics of minimal residual disease after treatment in AML patients.

PMID- 15493583
TI  - [Plasminogen activator inhibitor-1 in the evolution of stroke].
AB  - Fibrinolytic activity in the acute stroke was examined by monitoring the level of
      plasminogen activator inhibitor-1 (PAI-1), as one of the indicators of
      fibrinolytic activity. Given the role of PAI-1 in the processes of atherogenesis
      and thrombogenesis, plasma PAI-1 level was measured in 59 patients (up to 50
      years of age) with atherothrombotic stroke (verified by computed tomography
      scanning or magnetic resonance imaging of brain) in the period from 12 to 24
      hours (I analysis) and 30 days after the onset of stroke (II analysis); then, it
      was correlated with plasma PAI-1 level in the control group (57 healthy
      subjects), which was 2.86 +/- 0.70 U/ml. It was found that PAI-1 level was
      significantly higher in the acute stroke (I analysis: PAI-1 = 4.10 +/- 1.40 U/ml,
      p < 0.001; II analysis: PAI-1 = 3.64 +/- 0.90 U/ml, p < 0.001), while
      fibrinolytic activity was lower, especially on the first day from the stroke that
      was not completely increased even after 30 days. There was no difference in PAI-1
      levels between the subgroups of patients with infarction and lacunar cerebral
      ischemia (p > 0.05), as well as between females and males (p > 0.05). Along with
      significantly increased fibrinogen level (4.65 +/- 1 g/l, in the controls--2.83
      +/- 0.64 g/l, p < 0.001), significantly higher triglycerides (2.04 +/- 0.76
      mmol/l, in the controls--1.38 +/- 0.54 mmol/l, p < 0.001) and lipoproteins(a)
      (0.405 +/- 0.29 g/l, in the controls--0.172 +/- 0.14 g/l, p < 0.001) were found,
      correlating with higher plasma PAI-1 level in these patients. The increased
      plasma level of PAI-1 pointed to possibility of decreased fibrinolytic activity
      in pathogenesis of ischemic stroke, as well as, risk of reinsult, which had been
      the greatest after the onset of stroke and declined gradually within several
      weeks.

PMID- 15493584
TI  - [Mucociliary transport in Eustachian tubes in chronic suppurative otitis media].
AB  - Eustachian tube dysfunction is one of the well-known factors leading to
      development of chronic suppurative otitis media. Tube mucociliary transport is
      important for elimination of the inflammation products from the middle ear
      enabling recovery of the affected mucosa of the middle ear, local circulation and
      restoration of normal air pressure in the middle ear. The study was aimed at
      determining: 1. whether perforation site on the tympanic membrane influences tube
      mucociliary transport time in individuals with traumatic rupture of the eardrum;
      2. possible time difference of tube mucociliary transport between group of
      patients with chronic suppurative otitis media and group of patients with
      traumatic rupture of the tympanic membrane; 3. possible time difference of tube
      mucociliary transport between chronic tubotympanic type of suppurative otitis
      media, so called tubotympanic otitis media and atticoantral type of chronic
      suppurative otitis media, the so called atticoantral otitis; 4. the association
      between the degree of defect of the tympanic membrane mucosa and time of tube
      mucociliary transport in each individual type of chronic suppurative inflammation
      of the middle ear. Eustachian tube mucociliary transport was studied in 16
      patients with tubotympanic otitis, in 13 patients with atticoantral otitis and in
      9 patients with traumatic rupture of the eardrum (control group of patients). All
      patients were treated at the Institute of Otorhinolaryngology and Maxillofacial
      Surgery, Clinical Centre of Serbia in Belgrade during 2002. Tube mucociliary
      transport was studied upon instillation of 10 microl 5% sterile saccharine
      solution through the existing eardrum perforation in the course of preoperative
      preparation of the patient for surgical intervention. The time interval from the
      moment of sterile saccharine solution application till perception of the sweet
      taste in the mouth and pharynx was measured in studied patients. The obtained
      results were analyzed using the methods of descriptive and analytical statistics
      (t-test for small independent samples). The mean time of tube mucociliary
      transport in patients with traumatic rupture of the tympanic membrane was 7.6
      minutes. The mean time of tube mucociliary transport in tubotympanic otitis with
      normal mucosa of the tympanic cavity promontorium was 15 minutes, while mean time
      of tube mucociliary transport in tubotympanic otitis with polypoid changes of the
      promontory mucosa was 24 minutes (t = 5.218; p < 0.01). Mean time of tube
      mucociliary transport in atticoantral otitis with normal promontory mucosa of the
      tympanic cavity was 35.5 minutes, while mean time of mucociliary tube transport
      in atticoantral otitis with polypold changes of promontory mucosa was 48 minutes
      (t = 6.99; p < 0.01). In the irreversibly changed tympanic cavity mucosa, tube
      clearance saccharine test was negative even after one hour. The results of our
      study indicate the possibility that prolonged mucociliary tube transport has
      greater influence to development of atticoantral otitis rather than to
      development of tubotympanic otitis. The association between the degree of mucosal
      defect and time of mucocillary transport was evidenced in both types of chronic
      suppurative inflammation of the middle ear.

PMID- 15493585
TI  - [Frequency of the external resorptions of tooth roots].
AB  - Root resorptions present a significant problem in endodontic therapy of the
      affected teeth and in dentistry in general. The objective of this study was to
      analyze, based on epidemiological and statistical research, the frequency of
      clinical incidence of pathological root resorptions in everyday practice related
      to localization, type of tooth, age and sex of patients. Radiographic
      documentation of patients treated from 1997 till 2002 at the Department of
      Conservative Dentistry and Endodontics, Faculty of Stomatology in Belgrade, was
      used as baseline for this study. Retroalveolar radiographs of teeth with visible
      signs of resorptions were singled out from 15654 patients' clinical records used
      for this study. The external resorptions were shown as radiolucent areas
      localized on various outer root surfaces, followed by significant or less
      significant resorption of lamina dura and alveolar bone. Out of all teeth
      analyzed in this study, 594 (3.79%) showed some kind of resorption. The external
      resorptions were found to be more present in the upper jaw (55.10%) and molars
      (50.30%) than in the lower jaw (44.90%) and single root teeth (49.70%), but in
      both cases without significant statistical differences. The most frequent
      localization of resorptions was root apex (82.44%). In regard to age, the most
      frequent resorptions were recorded in patients aged between 21 and 30 years
      (28.40%), and the lowest incidence was found in the youngest population (5.51%).
      The results also showed that resorptions were more frequent among the female
      population (59.04%) than among the male population (40.96%). Based on these
      results, we may conclude that the external root resorptions are not a frequent
      clinical phenomenon. Proper and early diagnostics of such tissue pathology is one
      of the basic prerequisites for successful endodontic therapy of the affected
      root.

PMID- 15493586
TI  - [Axillobifemoral bypass grafting].
AB  - INTRODUCTION: Axillo-femoral bypass (AxF) means connecting the axillar and
      femoral artery with the graft that is placed subcutaneously. Usually, this graft
      is connected with contralateral femoral artery via one accessory subcutaneous
      graft, and this connection is known as axillobifemoral bypass (AxFF). This extra
      anatomic procedure is an alternative method to the standard reconstruction of
      aortoiliac region when there are contraindications for general or local reasons.
      OBJECTIVE: The objective of this paper is to show early and late results of AxFF
      bypass grafting as well as to show the indications for AxFF bypass. METHODS: The
      sample consisted of 37 patients. The procedure was performed in 28 patients who
      suffered from aortoiliac occlusive disease and who were at high risk due to the
      comorbidity--in one patient with the rupture of juxtarenal aneurysm of abdominal
      aorta; in five patients with aortoenteric fistula, in two patients with
      latrogenic lesion of abdominal aorta and in one female patient with anus
      preternaturalis definitivus who was treated for rectovaginal fistula. Donor's
      right axillary artery was used in 26 cases (70.3%), and donor's left axillary
      artery was used in 9 cases (29.7%). Dacron graft was used in 34 patients and
      Polytetrafluoroethlylene graft was used in three patients. Simultaneously,
      profundoplastic was done in four patients and femoro-popliteal bypass was
      performed in three patients. In five patients who suffered from aortoenteric
      fistula, simultaneous intervention of gastrointerstinal system has been done.
      Chi2 test was used for statistical evaluation and life table method was used for
      verification of late graft patency. RESULTS: The rate of early postoperative
      mortality was 13.5%. The causes of death were: sepsis--1, MOFS--3, and infarct
      myocardium--1. The mean follow up period was 40.1 months, ranging from six months
      to 17 years. During the follow up period, an early graft thrombosis was
      identified in two and late graft occlusion was reported in four patients. As the
      cause of occlusion, the progression of occlusive disease of receptive artery was
      identified in three patients, while anastomotic neointimae hyperplasia of
      recipient artery was identified in one patient. Three patients died during the
      follow up period. As the cause of death, CVI was reported in two patients and
      malignancy of the urinary tract was found in one patient. The other complications
      were--artery angulation on the level of proximal anastomosis in one patient
      (Figure 1), false aneurysm in one patient, perigraft seroma in one patient and
      graft infection in three patients. Life table method has shown that cumulative
      rate of late graft patency is 80.39% after five years (Graph 1). DISCUSSION: Our
      results were analyzed and compared with the results of the study on 283 patients
      who had undergone aortobifemoral bypass (AFF) operation due to the aortoiliac
      occlusive disease. This study was completed in 1995 (18). The results showed that
      there was no statistically significant differences between AxFF and AFF group (p
      > 0.05), considering early mortality rate and late graft patency (Graph 2). The
      review of mortality and late patency rate after AxFF bypass grafting in a world
      well known studies has shown the similar results (Table 1). CONCLUSION The
      authors suggest that axilobifemoral bypass is indicated when there are
      contraindications or difficulties to perform anatomic reconstruction due to the
      abdomen condition (infection, adhesion, comorbidity) as well as in high risk
      patients with low life expectancy.

PMID- 15493587
TI  - [Conservative treatment of ectopic pregnancies: comparison of velocity of
      decrease of beta-HCG between spontaneous and methotrexate induced resorptions].
AB  - The evolution of the process can take two different directions. If an Intact
      pregnancy continues to grow, there is a tubal abortion or a rupture of the
      Fallopian tube. In the oppsote case, there is spontaneous resorption of the tubal
      pregnancy. In certain cases with the application of methotrexate, the ectopic
      pregnancy growth can be interrupted and spontaneous resorption can be induced.
      Nowadays, the international standards of treating patients with early ectopic
      gravidities and no peritoneal effusions, with beta-HCG values below 6000 UI/l,
      gestational sac diameter below 3 cm, and without any visible heart action, imply
      methotrexate treatment. The objective of this study is to prove the efficiency of
      methotrexate use in patients who meet the above criteria. The first group did not
      manifest satisfying decrease of [beta-HCG after two measurements, so methotrexate
      was used, while the second group showed satisfying decrease of beta-HCG, measured
      on the third day. Comparing the velocity of decrease of beta-HCG level among both
      groups of patients, it was proved that iatrogenically induced decrease, that is
      to say the achieved resorption, was equal to the spontaneous resorption, which
      justified the use of methotrexate in ectopic pregnancy treatment.

PMID- 15493588
TI  - [Correlation between the survival duration and trauma severity in persons who
      died from posttraumatic fat embolism].
AB  - INTRODUCTION: Posttraumatic fat embolism follows the injury. The fat emboli in
      circulation could cause death in three ways: isolated lung fat embolism, systemic
      fat embolism and fat embolism syndrome (FES). In forensic pathology, only two
      trauma scores, based on disintegration of anatomic structures, could be used for
      objectivization, comparison and establishment of severity of injuries. One of
      them is Injury Severity Score--ISS, based on Abbreviated Injury Scale--AIS. The
      second one is Hannover Polytrauma Score--HPTS, based on the total sum of all
      injuries and age of the injured person. OBJECTIVE: The objectives of this paper
      were to establish the correlation between outliving period and trauma severity
      (based on ISS and HPTS values), in persons died from posttraumatic fat embolism
      and/or its complications, and to establish which of these score systems could be
      better for prediction of development of the posttraumatic fat embolism. METHOD:
      The retrospective autopsy study was performed and it included the material of the
      Institute of Forensic Medicine in Belgrade for period 1988-2001. The autopsy
      reports and clinical medical data were analyzed, for persons died from
      posttraumatic fat embolism and/or its complications. In all cases, the fat
      embolism was the single cause of death, verified by autopsy. In each case, ISS
      and HPTS values were obtained. The sample was statistically prepared (chi2 test,
      correlation coefficient, regression line). RESULTS AND DISCUSSION: The sample
      included 50 persons: 41 males and 9 females. The proportion of men was
      statistically significant (chi2 = 20.480; p < 0.001). Average age of male was
      55.26 years (SD = 21.39) and of female was 55.78 (SD = 17.45). There was no
      statistically significant disproportion among the age distribution of the sample
      (chi2 = 6.4; p > 0.05). The outliving period varied from 1-14 days: the average
      was 5.92 (SD = 3.39; Med. 5.50; Mod. 2). The average value of 1SS was 19 (SD =
      7.70; Med. 19; Mod. 14), and for HPTS average value was 28.16 (SD = 12.87; Med.
      26.50; Mod. 12). In literature, there have been data about critical ISS value: 12
      20. HPTS value of 20 to 35 was lethal in 25%. Each injured of our sample had, at
      least, one long bone or pelvic fracture. There was negligible negative
      correlation between outliving period and 1SS and HPTS values in our sample:
      coefficient of linear correlation r = -0.117, t = 0.83 and r = -0.088, t = 0.59.
      Our sample was representative (t = 8.37). These data pointed out that the
      outliving period of the observed patients, died from post-traumatic fat embolism,
      was not in relation to general severity of injuries but to fat embolism per se
      and its consequences. There was low positive correlation between ISS and HPTS
      values: r = 0.296, t = 2.147, coefficient of determination r2 = 0.0876 and linear
      regression HPTS = 18.7588+0.4948 ISS. These data indicated that direct
      correlation between scores was only about 9% and the rest of correlation i.e. 91%
      depended on other factors. CONCLUSION: There was negative negligible correlation
      between outliving period and severity of injury based on ISS and HPTS, in
      patients died from posttraumatic fat embolism. So, these score systems are
      useless for prediction of duration of the outliving period in the injured died
      from fat embolism as well as for prediction of posttraumatic fat embolism as
      cause of death.

PMID- 15493589
TI  - [Aplastic anaemia caused by thiamazole--a case report].
AB  - Antithyreoid drugs are known causative agents of agranulocytosis and, in rare
      cases, aplastic anaemia as well. This is a case report of a female patient with
      secondary aplastic anaemia developed two years after continual use of thiamazole.
      She suffered from exhaustion and massive epistaxis. Physical examination revealed
      pale skin and mucous membranes, skin hematomas (body and legs) and high body
      temperature--39 degrees C. At admission, her blood film revealed pancytopaenia
      with 75 g/l hemoglobin concentration, 1.0 x 10(9)/l leukocytes and severe
      thrombocytopaenia--7.0 x 10(9)/l. Differential count showed 91% of lymphocytes,
      1% of monocytes and only 8% of neuthrophils. Bone marrow cytology and
      pathohistologic findings revealed severe hypocellularity, replaced with fat cells
      and only 10% of active hematopoietic tissue. In the acute phase of illness, in
      vitro growth of bone marrow progenitors was completely absent. Treatment was
      initiated with prednisone and danazol. During that time, she suffered from
      epistaxis, gastro-intestinal bleeding and herpes infection. Due to therapeutic
      failure cyclosporine A was added after 21 days. There upon, slow recovery ensued.
      After two months, she was discharged from hospital with stable blood film
      findings (HB 83 g/l, WBC 4.6 x 10(9)/l, and PLT 30.0 x 10(9)/l). She was
      forbidden thiamazole for her life time. After recovery from the acute phase of
      illness, in vitro haematopoietic precursor cells examination was repeated. The
      number of CFU-E colonies stimulated with 1 IU EPO was decreased in comparison
      with the control values. Upon adding 100 micro/l of thiamazole (5 mg/ml
      concentration e.g. 500 mg per culture), the growth of CFU-E was completely
      prevented, followed by marked cytotoxicity signs. The treatment including low
      doses (5 mg/ kg body weight daily) of cyclosporine A administration was continued
      on outpatient basis. After one year, blood film showed almost normal results with
      120 g/l hemoglobin concentration, 4.3x10(9)/l leukocytes and mild
      thrombocytopaenia 72.0 x 10(9)/l. She was transfusion free.

PMID- 15493590
TI  - [Diagnostics of mucopolysaccharidoses presented through the case of Sanfilippo
      syndrome].
AB  - Mucopolysaccharidoses (MPS) are recessive inheritable, progressive diseases of
      disordered degradation and storage of acid glucosaminoglycans. A five-year old
      child with psychomotor development retardation, which started at his age of two,
      was presented in our study. Clinical examination showed big head with rough
      facial features, skeleton deformities and hepatosplenomegaly. The diagnosis
      Dysostosis epifisealis multiplex was also confirmed by the X-ray examination of
      skeleton. Karyotype: 46, XY. Mental retardation: IQ--48. Clinically suspected
      mucopolysaccharidosis called for metabolic screening of first morning urine and
      the positive toluidine blue test result indicated the increased excretion of
      mucopolysaccharides. Further enzyme analyses of peripheral blood leucocytes
      confirmed the heparin sulphate sulphatase deficiency on the basis of which A (MPS
      III) Sanfilippo syndrome was defined. Our patient was born as a twin sibling. The
      other sibling is clinically healthy and of normal metabolic screening. It was not
      possible to define precisely the healthy heterozygote by testing the enzyme
      activities. A large number of mutations at various loci and big genetic
      heterogeneity of mucopolysaccharidoses made molecular diagnostics difficult. In
      the subsequent pregnancy, the mother was recommended prenatal diagnostics by
      enzyme analysis from the cultured chorionic villus. The prognosis of the
      presented patient is bad, the course of the disease is progressive and the
      patient can be expected to die in spastic tetraplegia in the second decade of
      life. The treatment is symptomatic for the time being.

PMID- 15493591
TI  - [Anomalous choledocho-pancretic ductal junction in a choledochal cyst--a case
      report].
AB  - Choledochal cysts are rare congenital anomalies, mostly detected in adults.
      Pathogenesis of these cysts seems to be in anomalous junction between pancreatic
      and common bile duct, above the papillary sphincter and outside of the duodenal
      wall. The absence of the sphincter above the junction is followed by reflux of
      the pancreatic juice into the bile duct leading to dilatation and fibrous changes
      of bile duct wall. A 38-year-old female is presented in whom a choledochal cyst
      was found 11 years earlier, during the operation performed for obstructive
      jaundice, when cystojejunostomy with Roux-en Y Jejunal limb was carried out. In
      February 1990, she was admitted to our Institution forjaundice and biliary colic.
      The patient was reoperated. Operative cholangiography showed an anomalous
      pancreatobiliary junction, choledochal cyst, dilated cystic duct and moderate
      dilatation of intrahepatic bile ducts. Cholecystectomy, desanastomosis with
      partial excision of choledochal cyst, and retrocolic choledochojejunostomy with
      the same Roux-en-Y jejunal limb were performed. Total excision of choledochal
      cyst was too risky due to chronic inflammatory changes in the hepatoduodenal
      ligament. Postoperative recovery was uneventful and the patient remained symptom
      free so far.

PMID- 15493592
TI  - [Systemic inflammatory response syndrome in surgical patients with sepsis].
AB  - Systemic inflammatory response syndrome and sepsis are common in surgically
      treated patients. Systemic inflammatory response syndrome represents a major
      factor of morbidity and mortality in these patients. The pathogenesis of these
      syndromes has been increasingly clarified. The objective of this review is to
      present an overview of our current understanding of the physiology underlying
      these conditions.

PMID- 15493593
TI  - [Interaction involving the thymus and the hypothalamus-pituitary axis,
      immunomodulation by hormones].
AB  - Perfectly projected and impeccably created, the endocrine system precisely
      regulates the most delicate immune processes. The immune and neuroendocrine
      systems are two essential physiological components of mammalian organisms
      important for protection from the infection and disease on one hand, and on the
      other, for regulation of metabolism and other physiological activities; namely,
      the evidence has been found indicating that there is active and dynamic
      collaboration of these systems in the execution of their designated functions.
      These interactions occur at many stages of embryonic and neonatal development,
      and they are a continual part of normal homeostatic balance necessary to preserve
      health. There is communication between neuroendocrine and immune system via
      cytokines, neurotransmitters and peptide hormones which act, in both systems,,
      through the same receptor molecules (Scheme 1). Many investigators have reported
      the increased thymic weight in experimental animals due to both castration and
      adrenalectomy. The discovery from 1898 revealing that thymus was enlarged in
      castrated rabbits has been considered the embryo of hybrid medical discipline,
      i.e. the immunoendocrinology. In the actual literature, at least in that
      available to us, it has not been noted that the appearance of the eunuchs, i.e.
      the castrates, stimulated the analytical approach to this phenomenon. Endocrine
      influences appear to be a part of bidirectional circuitry, namely, thymic
      hormones also regulate the release of hormones from the pituitary gland.
      Physiologically, thymus is under neuroendocrine control. It is apparent that the
      circulating levels of distinct peptide hormones are necessary to maintain a
      series of biological functions related both to microenvironmental and lymphoid
      cells of the organ. The neuroendocrine control of the thymus appears to be
      extremely complex, with apparent presence of complete Intrathymic biological
      circuitry involving the production of pituitary hormones, as well as the
      expression of their respective receptors by thymic cell. The influence of
      gonadectomy on the humoral immunity has been controversial. All investigations
      agree that women have higher titres of all classes of circulating antibodies than
      men. The application of estrogens stimulated the formation of antibodies in the
      circulation. Then, if there were no sex glands, the immune response of the
      individual would be enhanced. Both the cellular and the humoral immune response
      is more powerful in the adult normal women than in men of the same age. The
      immune response is different in different sexes meaning that there is a sexual
      dimorphism. This difference has not been noted before the puberty. It has been
      noticed that the substitution therapy has alleviated the late skin
      hypersensitivity. The estrogens have also curtailed the rejection time of the
      transplant and all reactions in which T-effector lymphocytes have been involved.
      NK-cells and T-lymphocytes activities have been decreased by the action of
      estrogens, as well as the release of thymus hormones. Cortical RE cells express a
      surface antigen, gp200-MR6, which plays a significant role in thymocyte
      differentiation. Irrespectively of which pathway may be triggered by
      neuroendocrine factors, the effects are pleiotropic and result in modulation of
      the expression of several genes in different cell types. Thymic neuroendocrine
      polypeptides are the source of self-antigens presented by MHC molecules enabling
      the differentiation of haematopoietic stem cells. Thymic nurse cells also produce
      thymosins beta 3 and beta 4 and display a neuroendocrine cell specific
      immunophenotype (IP): Thy-1+, A2B5+, TT+, TE4+, UJ13/A+, UJ127.11+, UJ167.11+,
      UJ181.4+ and presence of common leukocyte antigen (CLA+). GH enhances thymocyte
      release from TNCs, as well as the reconstitution of these lymphoepithelial
      complexes. Similarto its role as a regulator of bone metabolism through
      regulating osteoprotegerin (OPG) production, the estrogen is involved in the
      processes of thymocyte development although aromatase mRNA has not been
      detectable in the thymus. While the increase of TNC number during lactation may
      be linked to the process of reconstruction of the thymic lymphoid population, the
      increased activity of lymphoepithelial interactions on GD14 may be associated
      with thymic engagement in pregnancy-induced immune processes The major antigens
      in the experimental autoimmune hypophysitis in rats are growth hormone,
      thyrotropin, and luteinizing hormone. The intrathymic T-lymphocyte selection is a
      complex, multistep process, influenced by several functionally specialised RE
      cells and under immuno-neuroendocrine regulation control reflecting the dynamic
      changes of the mammalian organism. In HIV-1-infected adults treated with growth
      hormone, thymic mass and circulating naive CD4 T cells are increased. The
      treatment would be easier for the diseased, as well as to us, the physicians, if
      we were aware of two millennia old wisdom--that the disease is a visit of God.

PMID- 15493594
TI  - [Sudden cardiac death in athletes].
AB  - Sudden cardiac death in an athlete is rare and tragic event. An athlete's death
      draws high public attention given that athletes are considered the healthiest
      category of society. The vast majority of sudden cardiac death in young athletes
      is due to congenital cardiac malformations such as hypertrophic cardiomyopathy
      and various coronary artery anomalies. In athletes over age 35, the usual cause
      of sudden cardiac death is coronary artery disease. With each tragic death of a
      young athlete, there is a question why this tragedy has not been prevented. The
      American College of Sports Medicine and the American Heart Association recommend
      that a pre-participation exam should include a complete cardiovascular history
      and physical examination.

PMID- 15493595
TI  - [Physicians founders of orthopedic surgery in Serbia].
AB  - The beginnings of the development of orthopedic surgery in Serbia have been
      related to the name of Dr Nikola Krstic and his first radiography of the hand in
      1908. The foundation of the Orthopedic Ward, led by Dr Nikola Krstic, within the
      General State Hospital in Belgrade, in 1919, marks the definition of orthopedics
      as a separate branch of surgery. In addition to Dr Nikola Krstic, Dr Borivoje
      Lalovic and Temp. Docent Dr Borivoje Gradojevic, who published the first
      orthopedics textbook in Serbian in 1934, also worked at the orthopedic ward
      between the two world wars. The work at the orthopedic ward, which grew into a
      clinic in 1947, was continued by Prof. Dr Milos Simovic, Prof. Dr Svetislav
      Stojanovic and Prof. Dr Ljubisa Doric. Their successors would have high
      achievements: Prof. Dr Zivojin Bumbasirevic became the only orthopedist who was a
      regular member of the Serbian Academy of Sciences and Arts, and Chief of Staff Dr
      Predrag Klisic and Prof. Dr Branko Radulovic provide impetus for further
      development of orthopedics by founding Specialist Orthopedics Hospital "Banjica".

PMID- 15493596
TI  - What is ergonomics, how can it help in my practice?

PMID- 15493597
TI  - ONA strategies implement law to improve nurse staffing in Oregon.

PMID- 15493600
TI  - Health implications of climate change.

PMID- 15493601
TI  - Lents Clinic and cultural competency.

PMID- 15493602
TI  - Evaluation of the application of veterinary judgement in the pre-emptive cull of
      contiguous premises during the epidemic of foot-and-mouth disease in Cumbria in
      2001.
AB  - This paper presents a detailed analysis of the application of contiguous culling
      in Cumbria between May 1 and September 30, during the outbreak of foot-and-mouth
      disease in 2001. The analysis shows that the application of veterinary risk
      assessment and judgement identified and removed groups of susceptible stock which
      were at risk of direct transmission of infection and avoided infected animals
      being left that might have spread the disease. When compared with an automatic
      contiguous cull, fewer culls were made and some of these were reduced in scale,
      providing economies in the use of resources. The data suggest that farms
      contiguous to an infected premises faced a 5 per cent risk of infection by direct
      transmission and a 12 per cent risk of infection by indirect transmission.

PMID- 15493603
TI  - Clinical and pathological features of dilated cardiomyopathy in Holstein-Friesian
      cattle.
AB  - Dilated cardiomyopathy is a primary disease of the heart muscle that has been
      reported in Holstein-Friesian cattle worldwide in the past 20 years. Nine cases
      of the condition were compared in terms of their clinical and pathological
      characteristics with nine unaffected animals matched for age, sex and breed.
      Their clinical signs included right-sided heart failure with severe subcutaneous
      oedema, ascites and/or hydrothorax and distended jugular veins. There were no
      characteristic biochemical or haematological changes. Postmortem, the affected
      hearts were enlarged with all the chambers dilated and walls of variable
      thickness. In most cases the kidneys were pale with a pitted surface.
      Histologically there was marked perimysial and endomysial fibrosis, extensive
      loss of cardiomyocytes by coagulative or colliquative necrosis, increased
      variation in the cross-sectional area of the myocardial fibres, and multifocal
      disarray and vacuolation of myocytes. Scanning electron microscopy showed that in
      all cases there was a mild myocardial inflammatory infiltrate, either diffuse or
      multifocal, which was identified by immunohistochemical labelling as T cells.

PMID- 15493604
TI  - Biological availability of inhaled fluticasone propionate in horses.
AB  - Healthy horses received aerosolised, intranasal or oral doses of 3 mg of
      fluticasone propionate evenly divided over morning and evening treatments for
      seven days. The bioavailability of the drug was determined in terms of the
      suppression of the endogenous cortisol concentrations in the horses during the
      period of treatment. The horses which received the aerosolised drug had
      significantly lower concentrations of endogenous cortisol on days 5 and 8 than
      the horses which received aerosolised placebo. The horses which received nasal
      and oral doses of fluticasone propionate showed no significant changes in their
      endogenous cortisol concentrations.

PMID- 15493605
TI  - PCR detection of virulence genes and molecular epidemiology of STEC O157 isolates
      from French abattoirs.

PMID- 15493606
TI  - Nasal mycosis in two cats caused by Alternaria species.

PMID- 15493607
TI  - PrP polymorphisms in Spanish sheep affected with natural scrapie.

PMID- 15493608
TI  - Arachnomelia in four Italian brown calves.

PMID- 15493609
TI  - Isolation of Mycobacterium microti from a male Charolais-Hereford cross.

PMID- 15493610
TI  - Survey on the use of pain relief in cattle.

PMID- 15493611
TI  - Idiopathic necrotising enteritis in a dairy calf.

PMID- 15493612
TI  - Administration of and withdrawal periods for sulphadimidine solution.

PMID- 15493613
TI  - Availability of vets and veterinary services.

PMID- 15493614
TI  - Searching the literature.

PMID- 15493615
TI  - Postgraduate study groups.

PMID- 15493616
TI  - Badgers and bovine TB.

PMID- 15493617
TI  - Perils of pet pigs.

PMID- 15493619
TI  - [Surgical treatment of hepatocellular carcinoma].
AB  - Surgical treatment of hepatocellular carcinoma. The therapy of hepatocellular
      carcinoma (HCC) has got nowadays an important problem of medicine. The five year
      survival time has increased in the consequences of the last 25 year medical
      activities. The development of liver surgery, the introduction of aggressive
      surgical strategy, the prognosis of the disease and the special indication of the
      operation have had important factors in bettering of the results. The size and
      number of the tumor, the tumor-free region of the tissue resected, capsule
      building, and the venous infiltration are the most important factors influencing
      the survival time. The repeated resection in case of newly developed HCC has got
      also a result with 19-20 per cent of five year survival time. In cases of non
      resectable tumors the a la carte chemotherapy, radiofrequency, TACE for down
      staging produce an opportunity in 10-20% of tumors being resectable. The new
      combined surgical-oncologic-intervention strategies involve the two step and
      repeated interventions, the minimal invasive technique (MIT), the TACE and the a
      la carte chemotherapy. Liver transplantation can be carried out exclusively in
      tumors less than 3 cm and in those having no more than 3 metastases.

PMID- 15493618
TI  - [Gaucher's disease: pathogenesis, diagnosis and therapy].
AB  - Gaucher's disease is the most common lysosomal storage disorder. Gene defect
      leads to deficiency or decreased activity of glucocerebrosidase followed by the
      accumulation of glucosylceramide. Most frequently hepatosplenomegaly, anemia,
      skeletal and hematological abnormalities are present. Different types are known
      based on the clinical findings. Recently used enzyme replacement therapy seems to
      eliminate bone marrow transplantation and has favourable effects on symptoms and
      outcome. Development of gene therapy (reintroduction of missing DNA sequence)
      hints the possibility of real causal therapy of the disease.

PMID- 15493620
TI  - [Correlations between gastroesophageal reflux disease and obstructive sleep
      apnea].
AB  - INTRODUCTION: Several studies have reported an increased prevalence of
      gastroesophageal reflux disease in patients with obstructive sleep apnea. The
      increasingly negative intrathoracic and transdiaphragmatic pressure should
      facilitate of reflux-events during apnea. AIMS: The aim of the present study was
      to investigate whether there exists a link between endoscopic severity of reflux
      disease and the parameters of obstructive sleep apnea and the typical symptoms of
      reflux disease. METHODS: 57 patients with proven obstructive sleep apnea were
      divided into two groups according to the severity of the sleep apnea: "mild
      moderate"--apnea-hypopnea index > or = 5-30, n = 27, "severe"--apnea-hypopnea
      index > 30, n = 30. All patients underwent upper panendoscopy, apnea monitoring
      during the night and were asked about existing and frequency of typical reflux
      symptoms. RESULTS: All examined patients in both groups showed significant
      overweight and there was a positive correlation between body mass index and the
      degree of sleep apnea (p = 0.0002). The occurrence of erosive reflux disease was
      significantly higher in "severe" group (p = 0.0001). Using a logistic regression
      analysis a positive correlation was found between endoscopic severity of reflux
      disease and apnea-hypopnea index (p = 0.016). 49.5% of all patients experienced
      the typical symptoms of reflux disease at least three times a week and there was
      not significant difference between groups. CONCLUSION: The study reveals that in
      patients with severe obstructive sleep apnea, erosive reflux disease is more
      frequent and a positive correlation can be found between severity of reflux
      disease and sleep apnea as well.

PMID- 15493621
TI  - [The non-lipid effects of statins].
AB  - In the past 15 years statins have gained recognition as one of the successful
      drugs in cardiovascular therapy and are now regarded as important as the beta
      blocking agents and ACE inhibitors. Since the publication of the Scandinavian
      Simvastatin Survival Study in 1994, the clinical application of statins has
      become increasingly widespread. Numerous large-scale clinical end-point trials
      have demonstrated that statin therapy reduces cardiovascular morbidity and
      mortality. Their beneficial therapeutic effects, besides their lipid lowering
      role, have been attributed to their non-lipid modifying ability, called the
      pleiotropic effect. The clinical consequences of the latter are not well
      understood, simply because differentiating between their lipid modifying and
      pleiotropic effects is not possible in vivo. In this article the authors
      summarize the evidence of the pleiotropic effects based on results of the latest
      in vitro experiments. They describe the influence of statins on endothelial
      dysfunction and thrombus formation, their anti-inflammatory, plaque-stabilizing
      and antioxidant effects, as well as their CRP and angiogenesis modifying non
      lipid effects. The authors further discuss the effects of these drugs on tumors,
      osteoporosis and dementia. Although all members of the statin family inhibit the
      same enzyme in the cholesterol synthesis (3-hydroxy-3-methylglutaryl coenzyme A
      reductase), their various pharmacokinetic properties, and tissue selectivity
      (lipophilicity and hydrophilicity) are responsible for their different
      pleiotropic effects.

PMID- 15493622
TI  - [For whom the ward round tolls. Medical rounds on hospital wards].

PMID- 15493623
TI  - [Treatment of diverticulosis and diverticulitis].

PMID- 15493624
TI  - Back to the future.

PMID- 15493625
TI  - A healthy home: UAMS College of Public Health is trying to right Arkansas' bad
      health ship.

PMID- 15493628
TI  - Public reporting now a reality for Medicare providers. Nursing homes, hospitals,
      home health agencies already reporting.

PMID- 15493626
TI  - James Fasules, MD.

PMID- 15493629
TI  - Peripheral magnetic resonance angiography.
AB  - Magnetic Resonance Angiography [MRA] has become a useful imaging modality in the
      evaluation of vascular anatomy and a variety of vascular disorders in the last
      several years. Many recent publications have demonstrated that MRA can be an
      accurate, fast and safe tool in the workup of patients with lower extremity
      ischemia. It has become a less invasive alternative to catheter angiography, and
      in some radiology departments MRA has replaced conventional catheter angiography
      in the initial workup of lower extremity ischemia.

PMID- 15493630
TI  - Introduction of the Master of Public Health program in Arkansas.

PMID- 15493631
TI  - [New dimension of the art of cell culturing].

PMID- 15493632
TI  - [Physicians without frontiers have reached a limit. The situation in Afghanistan
      stopped the risky work--uncertain future of the relief work].

PMID- 15493633
TI  - [Modern health care requires well-functioning infection clinics. It must be
      possible to isolate infected patients and to maintain basic hygiene routines].

PMID- 15493634
TI  - [Infection threat in the 21st century! Time to seriously consider the threats!
      Make health care and society prepared!].

PMID- 15493635
TI  - [Case report of an unusual complication. Splenic rupture after cardiopulmonary
      resuscitation and thrombolysis resulted in death].
AB  - Cardiopulmonary resuscitation (CPR) is associated with certain bleeding risks
      especially if thrombolysis is included in the treatment. Even though these risks
      are known it is not a contraindication with CPR after thrombolysis or
      thrombolysis after CPR. We present a case of a bleeding ruptured spleen after
      thrombolysis of the popliteal artery due to a occluded aneurysm in a patient with
      myocardial infarction and ventricular fibrillation. As for many others with this
      complication, the patient did not survive.

PMID- 15493636
TI  - [Life-long regular physical exercise is crucial in coronary disease].
AB  - Coronary heart disease, i.e. angina pectoris or myocardial infarction, is one of
      our most common diseases. Age, gender and heredity, as well as smoking,
      hypertension, physical inactivity, diabetes, overweight and stress are risk
      factors for the disease. Regular physical activity and exercise training
      positively influences several of these risk factors at the same time. The
      prescription for physical activity and training is life long and should include
      fitness as well as strength and endurance training. It is of great importance
      that the first period of rehabilitation, after an acute event, is carried out
      under supervision, preferably by a specialised physiotherapist. When the
      condition is stabilised, in most of the cases after 2-3 months, the training may
      be continued outside the hospital. Suitable activities are daily walks, jogging,
      cycling, swimming, aerobics, dance, ballgames etc depending on interest and
      physical condition.

PMID- 15493637
TI  - [Exciting findings can change the view on the pathogenesis of type 2 diabetes.
      Impaired mitochondrial function can explain metabolic disorders in several
      organs].

PMID- 15493638
TI  - [Independent competence evaluation during ongoing internship--support to general
      practitioners].

PMID- 15493639
TI  - [Jaw fixation--a parenthesis in the history of obesity treatment].

PMID- 15493640
TI  - [Mass media's reports on genital mutilation goes on].

PMID- 15493641
TI  - [A tiny, tiny incision can make a miracle].

PMID- 15493642
TI  - [Shortages in the management of genitally mutilated pregnant women in Swedish
      health care. Time to shift the focus from women's genitals to their whole being].

PMID- 15493643
TI  - [Models for future health care agreements are compiled without cooperation with
      physicians].

PMID- 15493644
TI  - [Documented advantages of insulin Lantus when compared with NPH insulin].

PMID- 15493645
TI  - [My quality of life has increased with Lantus].

PMID- 15493646
TI  - ["Proportion of contact"--good for what?].

PMID- 15493647
TI  - [Bad taste in the mouth because of the article on snuff use].

PMID- 15493648
TI  - A field guide to alternative healers. Your patients see them as well as you, so
      know who's out there.

PMID- 15493649
TI  - Stephen Barrett on unconventional therapies.

PMID- 15493650
TI  - Educating patients about alternative therapies.

PMID- 15493651
TI  - E-mail "visits" can save you time.

PMID- 15493652
TI  - What "tiered networks" will mean to you.

PMID- 15493653
TI  - Earnings. Primary care tries to hang on.

PMID- 15493654
TI  - Delivering test results.

PMID- 15493655
TI  - The country can't afford boutique medicine.

PMID- 15493657
TI  - Secondary ion mass spectrometry.

PMID- 15493656
TI  - The following is a response to "Computation of HORRAT values" [McClure, F.D., &
      Lee, J-K. (2003) J. AOAC Int. 86, 1056-1058].

PMID- 15493658
TI  - Determination of maduramicin in feedingstuffs and premixtures by liquid
      chromatography: development, validation, and interlaboratory study.
AB  - A reversed-phase liquid chromatography method for determination of maduramicin in
      feedingstuffs and premixtures was developed, validated, and interlaboratory
      studied. The extraction solvent was methanol. Maduramicin was detected at 520 nm
      after postcolumn derivatization with vanillin. Recovery was >90%. The
      repeatability relative standard deviation (RSDr) in feeds (1-5 mg/kg) and
      premixtures (500 mg/kg) ranged between 2.7 and 7.7%; the within-laboratory
      reproducibility was between 3.7 and 8.5%. The limit of quantitation was 2 mg/kg.
      Other feed additives did not interfere in the assay. The method showed ruggedness
      against small changes in the extraction conditions, eluant composition, and
      conditions for postcolumn derivatization. The presence of water in the extraction
      solvent negatively affected the recovery. In the collaborative study, 5 feeds (4
      positive at 2.5-9 mg/kg, 1 blank) and 1 premixture (450 mg/kg) were analyzed by
      10 laboratories. The RSDr of the feedingstuffs varied between 3.29 and 8.53%. The
      HORRAT ranged between 1.10 and 1.98. Recoveries were >90%, except for one
      participant (80%). One laboratory detected small signals in the blank sample,
      corresponding to 0.7 and 0.8 mg/kg. For the premixture, the RSDr was 3.15% and
      the HORRAT was 1.80.

PMID- 15493659
TI  - Liquid chromatographic determination of St. John's wort components in functional
      foods.
AB  - A method was developed for determination of St. John's wort marker compounds
      hypericin, pseudohypericin, hyperforin, and adhyperforin in functional foods.
      Solid-phase extraction provided analyte extraction and significant sample cleanup
      prior to analysis using liquid chromatography (LC) with UV and fluorescence
      detection. In addition to quantification using LC-UV, confirmation was made with
      electrospray ionization LC mass spectrometry (LC/MS). Several commercially
      available tea and drink products claiming to contain St. John's wort were tested.
      Recoveries ranged from 51 to 98% for the liquid samples. Comparison of the
      concentrations in 4 St. John's wort teas showed a variation in analyte
      concentration (1044-10 ng/mL marker compounds in brewed tea) and composition. No
      marker compounds were found in the beverages, indicating possible decomposition
      of the marker compounds caused by low pH and/or exposure to light. A solvent
      extraction procedure was developed for analysis of the marker compounds from
      solid samples. Analytes were detected at low parts per million, with an average
      recovery of 75%. No St. John's wort components were found in the 2 solid
      functional food samples analyzed.

PMID- 15493661
TI  - One internal standard for multiple analytes: a limit and solution.
AB  - The use of a single internal standard (ephedrine-d5) as the basis for
      calculations of the concentrations of both the major and the minor alkaloids
      leads to incorrect results from variabilities in the solid-phase extraction (SPE)
      of the ephedra alkaloids. Because the SPE column is overloaded by ephedrine, the
      recovery of the internal standard, which is dependent on the dilution factor, is
      decreased. On the other hand, the recoveries of the minor alkaloids
      (methylephedrine, methylpseudoephedrine, norephedrine, and norpseudoephedrine)
      stay high because these compounds are less concentrated and do not overload the
      SPE column. Consequently, the recovery factors for the major and minor alkaloids
      are different, or the results are incorrect if the same recovery factor is used.

PMID- 15493660
TI  - A rapid cleanup method for the isolation and concentration of pyrrolizidine
      alkaloids in comfrey root.
AB  - Preparations from comfrey (Symphytum officinale and S. x uplandicum) root and
      leaf contain varying levels of the hepatotoxic pyrrolizidine alkaloids (PAs).
      Reference compounds for comfrey are not commercially available, and there is
      currently no rapid extraction or analytical method capable of determining low
      levels in raw materials or as adulterants in commercially available extracts. A
      solid-phase extraction (SPE) method was developed using an Ergosil cleanup column
      that specifically binds the PAs. With this method, powdered comfrey root was
      extracted by sonication and shaking with basic chloroform. The extract was
      applied to the cleanup column under vacuum, washed with 2 mL acetone-chloroform
      (8 + 2, v/v) followed by 2 mL petroleum ether to remove excess chloroform. The
      column was dried under vacuum, and the PAs were eluted with 2 successive 1 mL
      aliquots methanol. Percent recoveries of the PAs following Ergosil SPE had an
      overall average of 96.8%, with RSD of 3.8% over a range of 1.0 to 25.0 g
      extracted in 100 mL. Average precision of the method (n = 3 over 4 extraction
      concentrations) gave an overall RSD of 6.0% for the 5 alkaloids, with a range of
      0.8% (5 g in 100 mL) to 11.2% (25 g in 100 mL). Recovery optimization testing
      showed that 1.0 g comfrey root extracted in 100 mL yielded the greatest recovery
      (% dry weight) of the PAs, with an extraction efficiency and accuracy of 94.2%,
      and RSD of 1.7% (n = 9). The unique properties of the Ergosil cleanup column
      provide rapid sample cleanup, volume reduction, and concentration of PAs from
      comfrey extracts, and allow the eluant to be analyzed directly by traditional
      chromatographic methods.

PMID- 15493662
TI  - Ultraviolet derivatization of steroidal saponin in garlic and commercial garlic
      products as p-nitrobenzoate for liquid chromatographic determination.
AB  - A method is described for determination of the steroidal saponin, eruboside B,
      originating in garlic and garlic products as the p-nitrobenzoyl chloride (PNBC)
      derivative by reversed-phase liquid chromatography (with ultraviolet detection at
      260 nm. Proto-eruboside B was extracted from garlic (Allium sativum L.);
      subjected to solid-phase extraction (SPE) with a C18 cartridge, Florisil column
      chromatography, and silica gel column chromatography; and then enzymatically
      converted to eruboside B, which was applied as an external standard. Steroidal
      saponins in garlic and commercial garlic products were extracted with methanol
      and purified by SPE cartridges, followed by enzymatic treatment. A frostanol
      saponin such as proto-eruboside B is enzymatically transformed to a spirostanol
      saponin, eruboside B. After the derivatization with PNBC, the saponin derivative
      was chromatographed on a C8 column with a gradient elution of (A) 80% aqueous
      acetonitrile and (B) 100% acetonitrile. The detection limit of the developed
      method was 1 microg/g for the samples. The method was applied to the analysis of
      garlic and garlic health food products available in Japan.

PMID- 15493663
TI  - Method for the determination of beta-carotene in supplements and raw materials by
      reversed-phase liquid chromatography: single laboratory validation.
AB  - A single laboratory validation (SLV) study was conducted for a liquid
      chromatography (LC) method for the determination of total and all-trans-beta
      carotene in a variety of dietary supplements, including multivitamin tablets,
      softgels, capsules, and beadlet raw materials. Extraction variants were developed
      for the different types of supplements tested based upon the supplement type and
      level of beta-carotene. Water dispersible formulations such as powders,
      emulsions, tablets, and capsules were enzymatically digested with protease and
      extracted with dichloromethane-ethanol. Oily suspensions were directly dissolved
      in dichloromethane-ethanol. After appropriate dilution or concentration, the
      extracts were chromatographed by using either a reversed-phase C18 column or, in
      products containing high amounts of alpha-carotene, a reversed-phase C30 column.
      The LC systems provided linear responses in the range of 0.1-50 microg beta
      carotene/mL. The main geometrical isomers of beta-carotene (all-trans, 9-cis, 13
      cis, and 15-cis) were well separated from each other and from other carotenoids
      such as a-carotene, cryptoxanthin, lutein, lycopene, and zeaxanthin. Duplicate
      determinations of total beta-carotene performed by 2 technicians in 8 different
      test materials on 5 different days resulted in relative standard deviations of
      1.2-4.4%. Recoveries determined for supplements and beadlet raw material spiked
      with beta-carotene levels of 10 microg to 100 mg/test portion and 0.2-40%,
      respectively, ranged from 97.5 to 102.1%. On the basis of the accuracy,
      precision, and recovery results from the SLV study, the method is suggested for a
      collaborative study on the determination of total and all-trans-beta-carotene in
      dietary supplements.

PMID- 15493664
TI  - Single laboratory validation of a method for determination of glucosamine in raw
      materials and dietary supplements containing glucosamine sulfate and/or
      glucosamine hydrochloride by high-performance liquid chromatography with FMOC-Su
      derivatization.
AB  - Single laboratory validation of a method for determination of glucosamine in raw
      materials and dietary supplements containing glucosamine sulfate and/or
      glucosamine hydrochloride by with high-performance liquid chromatography FMOC-Su
      derivatization. Tests with 2 blank matrixes containing SAMe, vitamin C, citric
      acid, chondroitin sulfates, methylsulfonylmethane, lemon juice concentrate, and
      other potential interferents showed the method to be selective and specific.
      Eight calibration curves prepared over 7 working days indicated excellent
      reproducibility with the linear range at least over 2.0-150 microg/mL, and
      determination coefficients >0.9999. Average spike recovery from the blank matrix
      (n = 8 over 2 days) was 93.5, 99.4, and 100.4% at respective spike levels of 15,
      100, and 150%, and from the sample matrix containing glucosamine (n = 3) was 99.9
      and 102.8% at respective levels of 10 and 40%, with relative standard deviations
      <0.9%. The method was also applied to 12 various glucosamine finished products
      and raw materials. The stability tests confirmed that glucosamine-FMOC-Su
      derivative once formed is stable at room temperature for at least 5 days. Limit
      of quantitation was 1 microg/mL and limit of detection was 0.3 microg/mL. The
      method is ready to proceed for the collaborative study.

PMID- 15493665
TI  - Development and validation of a liquid chromatographic method for fexofenadine
      hydrochloride in capsules.
AB  - This paper describes the development and validation of a new, simple, fast, and
      sensitive liquid chromatographic method for the determination of the
      antihistamine fexofenadine. Although widely used in the treatment of allergic
      diseases, fexofenadine is not listed in any pharmacopeia, and there are few
      methods in the literature for its quantitation in pharmaceutical dosage forms. In
      this work, a LiChrospher 100 RP-18 (250 x 4.0 mm, 5 microm) column was used as
      the stationary phase, and acetonitrile-5mM ammonium acetate buffer (50 + 50, v/v)
      at pH 3.2 was the mobile phase. Through the evaluation of the analytical
      parameters, it was shown that the method is linear (r = 0.9999) at concentrations
      ranging from 20.0 to 80.0 microg/mL, precise (intraday relative standard
      deviation [RSD] values = 0.85, 0.40, and 0.81%; interday RSD = 0.77%), accurate
      (mean recovery = 99.05%), specific, and robust. The detection and quantitation
      limits are 0.3409 and 1.033 microg/mL, respectively. These low values show the
      good sensitivity of the proposed method.

PMID- 15493666
TI  - Development and validation of a gas chromatography/mass spectrometry procedure
      for confirmation of para-toluenesulfonamide in edible fish fillet tissue.
AB  - Chloramine-T is a disinfectant being developed as a treatment for bacterial gill
      disease in cultured fish. As part of the drug approval process, a method is
      required for the confirmation of chloramine-T residues in edible fish tissue. The
      marker residue that will be used to determine the depletion of chloramine-T
      residues from the edible tissue of treated fish is para-toluenesulfonamide (p
      TSA), a metabolite of chloramine-T. The development and validation of a procedure
      for the confirmation of p-TSA is described. Homogenized fish tissue is dried by
      mixing with anhydrous sodium sulfate, and the mixture is extracted with methylene
      chloride. The extract is passed through a silica gel solid-phase extraction
      column, from which p-TSA is subsequently eluted with acetonitrile. The
      acetonitrile extract is evaporated, and the oily residue is dissolved in hexane.
      The hexane solution is shaken with fresh acetonitrile. The acetonitrile solution
      is evaporated and the residue is redissolved in dilute potassium hydroxide
      solution. The aqueous solution is extracted with methylene chloride to further
      remove more of the fat co-extractive. The aqueous solution is reacted with
      pentafluorobenzyl bromide in presence of tetrabutylammonium hydrogensulfate. The
      resulting di-(pentafluorobenzyl) derivative of p-TSA is analyzed by gas
      chromatography/mass spectrometry. This method permits the confirmation of p-TSA
      in edible fish tissue at 20 ppb.

PMID- 15493667
TI  - Evaluation of the swab test on premises for detection of antimicrobial residues
      in bovine and porcine kidneys.
AB  - The effect of sample matrix on the sensitivity of the Swab Test On Premises
      (STOP) was evaluated for selected antimicrobials. Fluid was extracted from bovine
      and porcine kidneys, and fortified with known levels of drugs. Aqueous standards
      were also prepared at the same levels. An aliquot of the fortified fluid or water
      was pipeted onto a dry swab which was placed onto the surface of a STOP plate,
      and the plate was incubated as outlined in the test kit manual. Zones of
      bacterial growth inhibition were measured and recorded, and additional testing
      was performed with decreasing levels of drug until a minimum detectable level was
      determined. The effect of temperature on the sensitivity of the test was also
      evaluated by running samples in duplicate, one set at a nominal temperature of 28
      degrees C, and the second set at a nominal temperature of 32 degrees C. Fortified
      bovine kidney fluid produced significantly larger zones than did porcine kidney
      fluid at both temperatures, but the mean zone sizes for fortified water were not
      significantly different from those of bovine or porcine kidney fluid at either
      temperature. For all 3 matrixes, zones of inhibition were significantly larger at
      28 degrees than 32 degrees C.

PMID- 15493668
TI  - Alternative anaerobic enrichments to the bacteriological analytical manual
      culture method for isolation of Shigella sonnei from selected types of fresh
      produce.
AB  - Alternative methods of reducing oxygen during anaerobic enrichment in the
      Bacteriological Analytical Manual (BAM) Shigella culture method were evaluated
      and compared to the current and less practical GasPak method. The alternative
      anaerobic methods included the use of reducing agents in Shigella broth and
      reducing culture container headspace volume to minimize atmospheric effects on
      oxygen concentration in Shigella broth during enrichment. The reducing agents
      evaluated were sodium thioglycollate, L-cystine, L-cysteine, titanium(III)
      citrate, and dithiothreitol, each at concentrations of 0.1, 0.05, and 0.01%. The
      use of Oxyrase for Broth with the enrichment medium (Shigella broth) was
      evaluated at concentrations of 10, 20 and 30 microL/mL. Recoveries of chill- and
      freeze-stressed S. sonnei strains 357 and 20143 were determined with each
      anaerobic method, including the GasPak method, using inoculation levels ranging
      from 10(0)to 10(3) cells. For each anaerobic method, strain, inoculation level,
      and stress type, 5 replicate enrichments were evaluated by streaking to MacConkey
      agar for isolation. The numbers of cultures with each method from which S. sonnei
      was isolated were used to compare the alternative anaerobic methods to the GasPak
      method. The alternative anaerobic method with which chill- and freeze-stressed S.
      sonnei strains 357 and 20143 were isolated most consistently was the use of
      Oxyrase for Broth in Shigella broth at a concentration of 20 microL/mL. This
      method was compared to the GasPak anaerobic method in evaluations on the recovery
      of S. sonnei strains 357 and 20143 from artificially contaminated test portions
      of parsley, cilantro, green onions, strawberries, carrots, and celery. A third
      anaerobic method included the use of 0.5 cm mineral oil overlay on cultures
      containing Oxyrase for Broth at concentrations of 20 microL/mL. Recovery rates of
      strain 357 were significantly greater (p < 0.05) with the GasPak method than with
      Oxyrase for Broth, with and without the 0.5 cm mineral oil overlay, for test
      portions of parsley, cilantro, and celery. When Oxyrase for Broth was used with
      Shigella broth, strain 357 was isolated at higher rates from all produce types,
      except cilantro, when 0.5 cm mineral oil overlay was applied to enrichment
      cultures. The use of mineral oil overlay with Oxyrase for Broth also improved
      recovery of strain 20143 from test portions of all produce types except green
      onion and strawberries. These differences were significant (p < 0.05) with
      parsley, carrots, and cilantro (1 of 2 evaluations). No statistically significant
      differences (p > 0.05) between the GasPak and Oxyrase for Broth anaerobic methods
      occurred when mineral oil overlay was used with Oxyrase for Broth. The use of
      Oxyrase for Broth with a 0.5 cm mineral oil overlay is a practical alternative
      for anaerobic enrichment with the BAM method in the analysis of some produce
      types. Differences in recovery among the different produce types and methods
      occurred between S. sonnei strains 357 and 20143, emphasizing the need for
      additional S. sonnei strains in future evaluations.

PMID- 15493669
TI  - Evaluation of VIDAS listeria monocytogenes II (LMO2) immunoassay method for the
      detection of Listeria monocytogenes in foods: collaborative study.
AB  - A multilaboratory study was conducted to compare the VIDAS Listeria monocytogenes
      II (LMO2) immunoassay and the standard cultural methods for the detection of
      Listeria monocytogenes in foods. Five food types-vanilla ice cream, brie cheese,
      cooked roast beef, frozen green beans, and frozen tilapia fish-at 3 levels were
      analyzed by each method. A total of 26 laboratories representing government and
      industry participated. In this study, 1404 test portions were analyzed of which
      1152 were used in the statistical analysis. There were 448 positive by the VIDAS
      LMO2 assay and 457 positive by the standard culture methods. A chi2 analysis of
      each of the 5 food types, at the 3 inoculation levels tested, was performed. The
      resulting chi2 value, 0.36, indicates that overall, there are no statistical
      differences between the VIDAS LMO2 assay and the standard methods at the 5% level
      of significance.

PMID- 15493670
TI  - Feasibility of reduction in use of the mouse bioassay: presence/absence screening
      for saxitoxin in frozen acidified mussel and oyster extracts from the coast of
      California with in vitro methods.
AB  - In the United States, the detection of paralytic shellfish poisoning (PSP) for
      regulatory purposes relies on the mouse bioassay (MBA). Using a saxitoxin
      presence/absence test could reduce animal usage significantly. Three in vitro
      methods, the RIDASCREEN Saxitoxin kit, MIST Alert, and a 5 h neuroblastoma assay,
      were evaluated in parallel with the MBA using 106 twice-frozen, acidified
      extracts from California-grown mussel and oyster tissues. For each assay, a
      cutoff point was established whereby data below or equal to that point were
      scored as negative and were assigned a score of zero. Data above the cutoff were
      considered positive and assigned a score of one. Pearson correlation coefficients
      were generated. The RIDASCREEN, MIST Alert, and neuroblastoma bioassay correlated
      to the MBA at 0.849, 0.853, and 0.832 when used for presence/absence detection.
      These data suggest that a reduction in MBA usage could be achieved in the
      surveillance of California-grown mussels and oysters for PSP-associated toxins.
      Correlation data between the in vitro assays, cost comparisons, and the potential
      for false negatives and false positives were examined. Implications of these
      methodologies in protecting public health are discussed.

PMID- 15493671
TI  - Immunoassay kit used to detect the presence of bovine material in processed
      foods.
AB  - The Tepnel Bio Kit for the detection of beef in cooked foods was assessed to
      determine its validity in demonstrating if food being imported into New Zealand
      contains beef material. The test suffered no interference from the presence of
      other common nonbovine species meats accepted as food within New Zealand and it
      detected beef in cooked samples of mixed meats when the proportion of beef in the
      mixture was >2 or >1%, depending on other meat species present. The documentation
      supplied with the kit indicates that the specific proteins it measures in cooked
      beef are stable to 130 degrees C. This was confirmed in the literature when the
      kit was used to test meat and bone meal cooked to at least 133 degrees C.
      However, our results showed these proteins to be much less stable when heated to
      elevated temperatures in moist food under pressure, and samples containing beef
      ceased to be positive by the immunoassay test after being autoclaved to 121
      degrees C. This suggests that the test may not be able to detect even relatively
      high levels of beef in low-acid canned foods, which are normally retorted under
      pressure to approximately 121 degrees C.

PMID- 15493672
TI  - Determination of lipid oxidation level in broiler meat by liquid chromatography.
AB  - An assay was conducted for the determination of malondialdehyde (MDA) levels in
      broiler meat. The method involves extraction of tissues with trichloroacetic acid
      (TCA) and reaction of the TCA extract with 2,4-dinitrophenylhydrazine (DNPH).
      After separation of the MDA-DNPH complex using a solid-phase extraction C18
      column, samples were eluted with 1 mL acetonitrile. Aliquots of 20 microL
      acetonitrile were analyzed by liquid chromatography on reversed-phase C18 column
      (3 microm) with UV detection. The products were eluted isocratically with the
      mobile phase containing acetonitrile-water-acetic acid (39 + 61 + 0.2, v/v/v).
      The retention time for MDA-DNPH was 6.5 min, and the detection limit was 3.5
      microg/kg. Two extraction methods (cold and hot) were also used in the study. The
      results showed that hot extraction increased results about 55.8% and recovery
      from samples spiked with 116.6 microg/kg was lower (74.6%) in comparison with
      cold extraction (94.7%).

PMID- 15493673
TI  - Detection and quantification of cocoa butter equivalents in cocoa butter and
      plain chocolate by gas liquid chromatography of triacylglycerols.
AB  - The development and in-house testing of a method for the detection and
      quantification of cocoa butter equivalents in cocoa butter and plain chocolate is
      described. A database consisting of the triacylglycerol profile of 74 genuine
      cocoa butter and 75 cocoa butter equivalent samples obtained by high-resolution
      capillary gas liquid chromatography was created, using a certified cocoa butter
      reference material (IRMM-801) for calibration purposes. Based on these data, a
      large number of cocoa butter/cocoa butter equivalent mixtures were arithmetically
      simulated. By subjecting the data set to various statistical tools, reliable
      models for both detection (univariate regression model) and quantification
      (multivariate model) were elaborated. Validation data sets consisting of a large
      number of samples (n = 4050 for detection, n = 1050 for quantification) were used
      to test the models. Excluding pure illipe fat samples from the data set, the
      detection limit was determined between 1 and 3% foreign fat in cocoa butter.
      Recalculated for a chocolate with a fat content of 30%, these figures are equal
      to 0.3-0.9% cocoa butter equivalent. For quantification, the average error for
      prediction was estimated to be 1.1% cocoa butter equivalent in cocoa butter,
      without prior knowledge of the materials used in the blend corresponding to 0.3%
      in chocolate (fat content 30%). The advantage of the approach is that by using
      IRMM-801 for calibration, the established mathematical decision rules can be
      transferred to every testing laboratory.

PMID- 15493674
TI  - Method validation for detection and quantification of cocoa butter equivalents in
      cocoa butter and plain chocolate.
AB  - A European interlaboratory study was conducted to validate an analytical
      procedure for the detection and quantification of cocoa butter equivalents in
      cocoa butter and plain chocolate. In principle, the fat obtained from plain
      chocolate according to the Soxhlet principle is separated by high-resolution
      capillary gas chromatography into triacylglycerol fractions according to their
      acyl-C-numbers, and within a given number, also according to unsaturation. The
      presence of cocoa butter equivalents is detected by linear regression analysis
      applied to the relative proportions of the 3 main triacylglycerol fractions of
      the fat analyzed. The amount of the cocoa butter equivalent admixture is
      estimated by partial least-squares regression analysis applied to the relative
      proportions of the 5 main triacylglycerols. Cocoa butter equivalent admixtures
      were detected down to a level of 2% related to the fat phase, corresponding to
      0.6% in chocolate (assumed fat content of chocolate, 30%), without false-positive
      or -negative results. By using a quantification model based on partial least
      squares regression analysis, the predicted cocoa butter equivalent amounts were
      in close agreement with the actual values. The applied model performed well at
      the level of the statutory limit of 5% cocoa butter equivalent addition to
      chocolate with a prediction error of 0.6%, assuming a chocolate fat content of
      30%.

PMID- 15493675
TI  - An interlaboratory-verified method for the determination of vitamins A and E in
      milk- and soy-based infant formula by liquid chromatography with matrix solid
      phase dispersion extraction.
AB  - An interlaboratory-verified, liquid chromatographic (LC) method is presented for
      determination of all-racemic alpha-tocopheryl acetate and retinyl palmitate in
      infant formula. The extraction procedure uses matrix solid-phase dispersion. A
      sample is mixed with C18, and the mixture is packed into a reservoir and eluted
      with selective solvents to extract the analytes. After evaporation and
      filtration, the sample extract is injected directly into a normal-phase LC system
      with fluorescence detection. All-racemic alpha-tocopheryl acetate and retinyl
      palmitate are quantitated isocratically with a mobile phase of hexane containing
      isopropanol at 0.2% (v/v) and 0.125% (v/v), respectively. A nonfortified zero
      control reference material (ZRM) was spiked at 5 levels, with 5 replicate
      analyses of 1/2x, x, 2x, 4x, and 16x where "x" represents the minimum levels of
      250 IU/100 kcal (vitamin A) and 0.7 IU/100 kcal (vitamin E) as specified in Title
      21 of the Code of Federal Regulations, part 107.100. Recoveries of retinyl
      palmitate ranged from 83.8 to 107%, and those of all-racemic alpha-tocopheryl
      acetate ranged from 87.7 to 108%. Two additional laboratories analyzed the ZRM
      samples at 4 spiking levels with 6 replicates. Recoveries of retinyl palmitate
      and all-racemic alpha-tocopheryl acetate ranged from 92.2 to 104% and from 91.7
      to 101%, respectively, in the second laboratory. Recoveries of retinyl palmitate
      and all-racemic alpha-tocopheryl acetate ranged from 85.3 to 97.0% and from 86.6
      to 110%, respectively, in the third laboratory. Relative standard deviations for
      all 3 laboratories ranged from 0.2 to 7.5% with an average of 2.9%. In addition,
      each laboratory analyzed a commercial milk- and commercial soy-based infant
      formula. Excellent agreement in results was obtained between the 3 laboratories
      for vitamins A and E in all matrixes.

PMID- 15493676
TI  - Gas chromatographic/mass spectrometric determination of 3-methoxy-1,2-propanediol
      and cyclic diglycerols, by-products of technical glycerol, in wine:
      interlaboratory study.
AB  - The aim of the present study was to provide the official wine control authorities
      with an internationally validated method for the determination of 3-methoxy-1,2
      propanediol (3-MPD) and cyclic diglycerols (CycDs)-both of which are recognized
      as impurities of technical glycerol-in different types of wine. Because glycerol
      gives a sweet flavor to wine and contributes to its full-body taste, an economic
      incentive is to add glycerol to a wine to mask its poor quality. Furthermore, it
      is known that glycerol, depending on whether it is produced from triglycerides or
      petrochemicals, may contain considerable amounts of 3-MPD in the first case or
      CycDs in the second. However, because these compounds are not natural wine
      components, it is possible to detect glycerol added to wine illegally by
      determining the above-mentioned by-products. To this end, one of the published
      methods was adopted, modified, and tested in a collaborative study. The method is
      based on gas chromatographic/mass spectrometric analysis of diethyl ether
      extracts after salting out with potassium carbonate. The interlaboratory study
      for the determination of 3-MPD and CycDs in wine was performed in 11 laboratories
      in 4 countries. Wine samples were prepared and sent to participants as 5 blind
      duplicate test materials and 1 single test material. The concentrations covered
      ranges of 0.1-0.8 mg/L for 3-MPD and 0.5-1.5 mg/L for CycDs. The precision of the
      method was within the range predicted by the Horwitz equation. HORRAT values
      obtained for 3-MPD ranged from 0.8 to 1.7, and those obtained for CycDs ranged
      from 0.9 to 1.3. Average recoveries were 104 and 109%, respectively.

PMID- 15493677
TI  - Simultaneous determination of saponins and isoflavones in soybean (Glycine max
      L.) by reversed-phase liquid chromatography with evaporative light-scattering and
      ultraviolet detection.
AB  - The first validated analytical method permitting the simultaneous qualitative and
      quantitative determination of isoflavones and saponins in soy has been developed.
      It combines liquid chromatography with an ultraviolet and evaporative light
      scattering detector (ELSD). Within less than 30 min, 6 isoflavones (detected at
      254 nm) and 4 triterpene saponins (monitored with the ELSD) were baseline
      separated, using a reversed-phase C18 column and a mobile phase consisting of
      water and acetonitrile, both containing 0.025% triflouroacetic acid. The method
      was validated for limit of detection (LOD), linearity, repeatability, precision,
      and accuracy. LOD was 3.2-6.0 ng/mL for isoflavones and 10.4-14.2 microg/mL for
      saponins, and linearity was indicated by R2-values of 0.997 and higher. Intra-
      and interday precisions of the assay were below 7.0% for all of the compounds
      except for one, which was only present in trace amounts in the samples.
      Repeatability was indicated by very stable retention times and relative standard
      deviations well below 4.0% for multiple injections (n = 3). Accuracy was
      confirmed by recovery rates between 96.8 and 101.0%, respectively. Different
      sample matrixes were successfully analyzed, proving the wide range of
      applicability of this method, including soybeans, capsules, liquids, and instant
      soy drinks.

PMID- 15493678
TI  - Polymerase chain reaction method to detect canis materials by amplification of
      species-specific DNA fragment.
AB  - Rapid identification of mammal materials in feeding stuffs and food is essential
      for effective control of a potential source of pathogens, such as those that
      cause bovine spongiform encephalopathy. A convenient polymerase chain reaction
      (PCR)-based assay was developed for detection and identification of a canis
      specific mitochondrial DNA sequence in foodstuffs and food. The amplified canis
      specific PCR product was a 213 base pair band from the D-loop DNA fragment of
      mitochondria, a high copy gene which should improve the possibility of amplifying
      template molecules of adequate size among the degraded DNA fragments brought
      about by heat denaturation. The specificity of this method was confirmed by 8
      canis blood DNA samples (from different breeds of dog) and 9 noncanis animal
      blood DNA samples (bovine, sheep, porcine, chicken, fish, donkey, rabbit, deer,
      horse). This method was able to detect the presence of canis material in
      foodstuffs and in food mixtures even when the concentration of canis-derived meat
      was reduced to 0.05%. Furthermore, it did not appear to be affected by prolonged
      heat treatment. This method was developed for detection of canis materials in
      feeding stuffs, and occasionally for medical jurisprudence detection of canis
      derived materials.

PMID- 15493679
TI  - Enzymatic, spectrophotometric determination of glucose, fructose, sucrose, and
      inulin/oligofructose in foods.
AB  - A fast, simple, and accurate method, using only standard laboratory equipment,
      was developed for the quantification of glucose, fructose, sucrose, and
      inulin/oligofructose in different food matrixes. Samples were extracted using
      boiling water and hydrolyzed with sucrase and fructanase. Sugars were determined
      in the initial extract and in both hydrolysates using an enzymatic,
      spectrophotometric kit for glucose and fructose determination with hexokinase,
      glucose-6-phosphate dehydrogenase, and phosphoglucose isomerase. Calculations of
      sucrose and inulin/oligofructose were based only on fructose measurement. Glucose
      results of the hydrolysates were not used for inulin/oligofructose calculations
      because of possible interference. Released glucose by the hydrolysis of maltose
      or by possible partial hydrolysis of other compounds like maltodextrines, starch,
      lactose, or maltitol could interfere in the measurement of the sucrase and the
      fructanase hydrolysates. To validate the method, a wide range of different food
      matrixes and different amounts of inulin/oligofructose (1-54%) were analyzed.
      Mean recovery +/- relative standard deviation (RSD) for inulin or oligofructose
      was 96.0 +/- 5.3%. The RSDr for inulin/oligofructose measured on 35 food samples,
      analyzed in duplicate, was 5.9%. Accuracy and precision of the method were less
      for samples with large concentrations of sucrose, maltose, maltodextrines, or
      starch (ratio to inulin/oligofructose >4 to 1). Precision and accuracy were
      comparable with those of the ion exchange chromatographic method AOAC 997.08 and
      the enzymatic, spectrophotometric method AOAC 999.03. In contrast to 999.03, this
      method allows the accurate quantification of both GFn and Fn forms.

PMID- 15493680
TI  - Application of rapid, electrochemical Flash Titration to total acidity and
      alkalinity determinations in buffers, foods, and beverages.
AB  - A new technique (Flash Titration) for the determination of total acidity and
      total alkalinity was applied to food and beverage analysis. Requiring no liquid
      titrants, Flash Titration is a technique made possible through microfabrication
      of electrochemical components on a silicon chip. Acidic or basic titrant was
      generated electrochemically at a noble-metal electrode that intimately surrounded
      an ion-selective, field-effect transistor pH sensor. As acid or base was
      generated through electrolysis, sample alkalinity or acidity, respectively, was
      neutralized in the immediate vicinity of the electrode. Through diffusion, a zone
      comprising a gradient of partially to totally neutralized sample expanded from
      the generating electrode into the volume element sensed by the nearby pH sensor.
      An analysis of the pH signal versus time revealed an end point inflection at an
      elapsed time related to the total alkalinity or acidity of the sample. End point
      times were typically a few seconds. In this paper, Flash Titration was applied to
      the analysis of a variety of samples, including juices, soft drinks, wines, and
      food products. The differences between the results obtained by the Flash
      Titration method and a commonly used conventional volumetric method were less
      than 2% in most food products tested. Analysis costs were reduced both through
      time saving and reduction or elimination of hazardous liquid titrant disposal, by
      the use of the Flash Titration method.

PMID- 15493681
TI  - Inductively coupled plasma compared with direct current arc spectrometry for
      analysis of minor elements in aluminium baths.
AB  - A validation study was carried out in order to evaluate the efficiency of
      inductively coupled plasma-optical emission spectrometry (ICP-OES) for the
      analysis of minor elements (manganese, chromium, copper, iron, and titanium) in
      aluminium alloys. Aluminium casting samples were obtained by adding compressed
      powder compacts of each alloying element and aluminium (minitablets) to aluminum
      baths in a laboratory crucible furnace. Digestion of solid samples was performed
      using concentrated HCI and H202 35% (v/v) previous to analysis by ICP-OES without
      any matrix separation. This solution-based method was validated considering
      direct current arc spectrometry as the reference method based on direct analysis
      without any pretreatment of the solid samples considered. Univariate statistical
      procedures were carried out, for which precision <3% and trueness of the
      analytical results were taken into account.

PMID- 15493682
TI  - A multiresidue pesticide monitoring procedure using gas chromatography/mass
      spectrometry and selected ion monitoring for the determination of pesticides
      containing nitrogen, sulfur, and/or oxygen in fruits and vegetables.
AB  - A procedure for the analysis of over 100 pesticides that only contain
      combinations of carbon, hydrogen, nitrogen, sulfur, and oxygen (i.e., no
      phosphorous or halogen atoms) has been developed. The procedure employs gas
      chromatography with a mass selective detector (GC/MSD), electron impact
      ionization, and selected ion monitoring. This GC/MSD procedure provided lower
      limits of quantitation and increased confirmational data compared to the
      traditional element-selective GC procedures that are commonly used for the
      detection of this "class" of pesticides. These analytical improvements were
      demonstrated by 26 pesticides that were detected at ng/g levels in a variety of
      fruit and vegetable matrixes using this procedure; these pesticides were missed
      by the traditional element-selective GC procedures. Validation of the procedure
      was performed using acetone extraction with solid-phase extraction cleanup.
      Twenty representative target pesticides were used to demonstrate repeatability
      and linearity of the chromatographic response and recovery from fruit and
      vegetable matrixes.

PMID- 15493683
TI  - Multiresidue method for N-methyl carbamates and metabolite pesticide residues at
      the parts-per-billion level in selected representative commodities of fruit and
      vegetable crop groups.
AB  - A reversed-phase liquid chromatographic method with both fluorescence and mass
      spectrometric detection is presented for the determination of 13 parent N-methyl
      carbamate pesticides and their metabolites, as well as piperonyl butoxide, for a
      total of 24 compounds in selected fruits and vegetables. The commodities chosen
      were of special concern to the U.S. Environmental Protection Agency (EPA) because
      they had the least amount of monitoring data for dietary exposure estimates used
      in risk assessment. The method is based on a judicious selection of procedures
      from U.S. Food and Drug Administration sources such as the Pesticide Analytical
      Manual (Volume I), and Laboratory Information Bulletins, plus additional material
      from the chemical literature combined in a manner to recover the N-methyl
      carbamates and their metabolites at the 1 microg/kg or 1 part-per-billion level.
      The method uses an acetone extraction, followed by an aminopropyl solid-phase
      extraction cleanup. Determination of residues is by RP-LC, in which the liquid
      chromatograph is interfaced with either a fluorescence or a mass spectrometric
      detector. The method is designed so that a set of 6 samples can be prepared in 1
      working day for overnight instrumental analysis. Recovery data are presented from
      analyses of selected commodities in some of EPA's fruit and vegetable crop
      groupings. A table listing relative retention times is presented for the N-methyl
      carbamates and their metabolites.

PMID- 15493684
TI  - A multicommutated flow system for determination of bismuth in milk shakes by
      hydride generation atomic fluorescence spectrometry incorporating on-line
      neutralization of waste effluent.
AB  - A highly sensitive method was developed for determination of bismuth in milk
      shakes by multicommutation hydride generation atomic fluorescence spectrometry
      (HG-AFS) based on off-line sonication for 10 min with aqua regia 8% (v/v) and on
      line waste treatment. The instrumentation and chemistry variables were studied in
      order to provide the best performance. The limit of detection in the original
      samples, established for a probability level of 99.6% (k = 3), was 1.67 ng/g Bi.
      The method provides a fast alternative in control analysis with a sampling
      throughput of 72 h as compared with 31 h obtained by the classical continuous
      measurement. Additionally, multicommutation reduces waste generation by a factor
      of 2.6. The consumption of sample, reductant, and blank, as compared with
      continuous mode HG-AFS, was reduced 9.6, 4.5, and 13.3 times, respectively. To
      confirm the accuracy of the method, recovery studies were performed, and
      excellent agreement between multicommutation and continuous measurement-based
      values was obtained. Application of the developed methodology for bismuth
      determination in milk shake samples from the Spanish market provided
      concentrations ranging from 4.2 to 15.0 ng/mL, and good comparability with data
      obtained by continuous measurements after microwave-assisted total digestion of
      samples for a 95% probability level and 12 degrees of freedom was found.

PMID- 15493685
TI  - Determination of the residues of eleven organophosphorus insecticides in Job's
      tears by gas chromatography with a nitrogen-phosphorus detector.
AB  - A simplified method for determining 11 organophosphorus insecticides (dichlorvos,
      methamidophos, acephate, diazinon, dimethoate, chlorpyrifos, malathion,
      parathion, quinalphos, methidathion, and ethion) in the Chinese herbal medicine
      Job's-tears is described. Standards were fortified into Job's-tears (5 g) at 4
      levels. The organophosphorus insecticides were extracted with dichloromethane and
      cleaned up with a mixture of Celite 545-activated carbon (4 + 1). The extracts
      were analyzed by gas chromatography using a nitrogen-phosphorus detector.
      Analysis of fortified Job's-tears shows average recoveries ranged from 73.90
      98.70%, 86.31-93.15%, 84.92-96.22%, and 83.29-104.23% at 0.05, 0.1, 0.5, and 1.0
      mg/kg levels, respectively. The minimum detectable amount ranged from 1.0 x 10(
      10) to 5.0 x 10(-10) g, and the limit of quantitation for the method was 0.05
      mg/kg. The method is rapid, simple, sensitive, reproducible, and applicable to
      the determination of these 11 organophosphorus insecticides in Job's-tears.

PMID- 15493686
TI  - Determination of sulfonamide residues in the tissues of food animals using
      automated precolumn derivatization and liquid chromatography with fluorescence
      detection.
AB  - A liquid chromatographic method for the determination of sulfachloropyridazine,
      sulfadiazine, sulfadimethoxine, sulfadoxine, sulfaethoxypyridazine,
      sulfamethazine, sulfaquinoxaline, and sulfathiazole residues in the muscle,
      liver, and kidney of food animals using sulfapyridine as internal standard is
      reported. Tissues are extracted using a modified version of AOAC Official Method
      983.31 (Sulfonamide Residues in Animal Tissues). The sample extract is
      reconstituted in pH 3.0 buffer-acetonitrile (60 + 40) and filtered into an
      autosampler vial. Using a programmable autosampler of a liquid chromatograph, a
      portion of the sample is derivatized precolumn with fluorescamine. The
      sulfonamide derivatives are separated by liquid chromatography using a C18 column
      with a mobile phase of 0.02M phosphoric acid-acetonitrile (60.5 + 39.5) and
      detected by fluorescence (excitation, 405 nm; emission, 495 nm). The method was
      applied to swine and cattle muscle, liver, and kidney; sheep and horse muscle and
      kidney; and chicken muscle and liver. The mean values for samples fortified with
      sulfonamides at levels between 0.05 and 0.2 microg/g agreed within 96-99% of
      spiked levels, with coefficients of variation ranging from 4-10%. The limit of
      detection (LOD) for all sulfonamides was 0.01 microg/g, with the exception of
      sulfaquinoxaline, for which the LOD was 0.015 microg/g.

PMID- 15493687
TI  - Detection of optic disc in retinal images by means of a geometrical model of
      vessel structure.
AB  - We present here a new method to identify the position of the optic disc (OD) in
      retinal fundus images. The method is based on the preliminary detection of the
      main retinal vessels. All retinal vessels originate from the OD and their path
      follows a similar directional pattern (parabolic course) in all images. To
      describe the general direction of retinal vessels at any given position in the
      image, a geometrical parametric model was proposed, where two of the model
      parameters are the coordinates of the OD center. Using as experimental data
      samples of vessel centerline points and corresponding vessel directions, provided
      by any vessel identification procedure, model parameters were identified by means
      of a simulated annealing optimization technique. These estimated values provide
      the coordinates of the center of OD. A Matlab prototype implementing this method
      was developed. An evaluation of the proposed procedure was performed using the
      set of 81 images from the STARE project, containing images from both normal and
      pathological subjects. The OD position was correctly identified in 79 out of 81
      images (98%), even in rather difficult pathological situations.

PMID- 15493688
TI  - Measurement of retinal vessel widths from fundus images based on 2-D modeling.
AB  - Changes in retinal vessel diameter are an important sign of diseases such as
      hypertension, arteriosclerosis and diabetes mellitus. Obtaining precise
      measurements of vascular widths is a critical and demanding process in automated
      retinal image analysis as the typical vessel is only a few pixels wide. This
      paper presents an algorithm to measure the vessel diameter to subpixel accuracy.
      The diameter measurement is based on a two-dimensional difference of Gaussian
      model, which is optimized to fit a two-dimensional intensity vessel segment. The
      performance of the method is evaluated against Brinchmann-Hansen's half height,
      Gregson's rectangular profile and Zhou's Gaussian model. Results from 100 sample
      profiles show that the presented algorithm is over 30% more precise than the
      compared techniques and is accurate to a third of a pixel.

PMID- 15493689
TI  - Overdetermined least-squares aberration estimates using common-midpoint signals.
AB  - As medical ultrasound imaging moves to larger apertures and higher frequencies,
      tissue sound-speed variations continue to limit resolution. In geophysical
      imaging, a standard approach for estimating near-surface aberrating delays is to
      analyze the time shifts between common-midpoint signals. This requires complete
      data-echoes from every source/receiver pair in the array. Unfocused common
      midpoint signals remain highly correlated in the presence of delay aberrations;
      there is also tremendous redundancy in the data. In medical ultrasound, this
      technique has been impaired by the wide-angle, random-scattering nature of
      tissue. This has made it difficult to estimate azimuth-dependent aberration
      profiles or to harness the full redundancy in the complete data. Prefiltering the
      data with two-dimensional fan filters mitigates these problems, permitting highly
      overdetermined, least-squares solutions for the aberration profiles at many
      steering angles. In experiments with a tissue-mimicking phantom target and
      silicone rubber aberrators at nonzero stand-off distances from a one-dimensional
      phased array, this overdetermined, fan-filtering algorithm significantly
      outperformed other phase-screen algorithms based on nearest-neighbor cross
      correlation, speckle brightness maximization, and common-midpoint signal
      analysis. Our results imply that there is still progress to be made in imaging
      with single-valued focusing operators. It also appears that the signal-to-noise
      penalty for using complete data sets is partially compensated by the
      overdetermined nature of the problem.

PMID- 15493690
TI  - A method for modeling noise in medical images.
AB  - We have developed a method to study the statistical properties of the noise found
      in various medical images. The method is specifically designed for types of noise
      with uncorrelated fluctuations. Such signal fluctuations generally originate in
      the physical processes of imaging rather than in the tissue textures. Various
      types of noise (e.g., photon, electronics, and quantization) often contribute to
      degrade medical images; the overall noise is generally assumed to be additive
      with a zero-mean, constant-variance Gaussian distribution. However, statistical
      analysis suggests that the noise variance could be better modeled by a nonlinear
      function of the image intensity depending on external parameters related to the
      image acquisition protocol. We present a method to extract the relationship
      between an image intensity and the noise variance and to evaluate the
      corresponding parameters. The method was applied successfully to magnetic
      resonance images with different acquisition sequences and to several types of X
      ray images.

PMID- 15493691
TI  - A similarity learning approach to content-based image retrieval: application to
      digital mammography.
AB  - In this paper, we describe an approach to content-based retrieval of medical
      images from a database, and provide a preliminary demonstration of our approach
      as applied to retrieval of digital mammograms. Content-based image retrieval
      (CBIR) refers to the retrieval of images from a database using information
      derived from the images themselves, rather than solely from accompanying text
      indices. In the medical-imaging context, the ultimate aim of CBIR is to provide
      radiologists with a diagnostic aid in the form of a display of relevant past
      cases, along with proven pathology and other suitable information. CBIR may also
      be useful as a training tool for medical students and residents. The goal of
      information retrieval is to recall from a database information that is relevant
      to the user's query. The most challenging aspect of CBIR is the definition of
      relevance (similarity), which is used to guide the retrieval machine. In this
      paper, we pursue a new approach, in which similarity is learned from training
      examples provided by human observers. Specifically, we explore the use of neural
      networks and support vector machines to predict the user's notion of similarity.
      Within this framework we propose using a hierarchal learning approach, which
      consists of a cascade of a binary classifier and a regression module to optimize
      retrieval effectiveness and efficiency. We also explore how to incorporate online
      human interaction to achieve relevance feedback in this learning framework. Our
      experiments are based on a database consisting of 76 mammograms, all of which
      contain clustered microcalcifications (MCs). Our goal is to retrieve mammogram
      images containing similar MC clusters to that in a query. The performance of the
      retrieval system is evaluated using precision-recall curves computed using a
      cross-validation procedure. Our experimental results demonstrate that: 1) the
      learning framework can accurately predict the perceptual similarity reported by
      human observers, thereby serving as a basis for CBIR; 2) the learning-based
      framework can significantly outperform a simple distance-based similarity metric;
      3) the use of the hierarchical two-stage network can improve retrieval
      performance; and 4) relevance feedback can be effectively incorporated into this
      learning framework to achieve improvement in retrieval precision based on online
      interaction with users; and 5) the retrieved images by the network can have
      predicting value for the disease condition of the query.

PMID- 15493692
TI  - Analysis of 3-D myocardial motion in tagged MR images using nonrigid image
      registration.
AB  - Tagged magnetic resonance imaging (MRI) is unique in its ability to noninvasively
      image the motion and deformation of the heart in vivo, but one of the fundamental
      reasons limiting its use in the clinical environment is the absence of automated
      tools to derive clinically useful information from tagged MR images. In this
      paper, we present a novel and fully automated technique based on nonrigid image
      registration using multilevel free-form deformations (MFFDs) for the analysis of
      myocardial motion using tagged MRI. The novel aspect of our technique is its
      integrated nature for tag localization and deformation field reconstruction using
      image registration and voxel based similarity measures. To extract the motion
      field within the myocardium during systole we register a sequence of images taken
      during systole to a set of reference images taken at end-diastole, maximizing the
      normalized mutual information between the images. We use both short-axis and long
      axis images of the heart to estimate the full four-dimensional motion field
      within the myocardium. We also present validation results from data acquired from
      twelve volunteers.

PMID- 15493693
TI  - Quantifying 3-D vascular structures in MRA images using hybrid PDE and geometric
      deformable models.
AB  - The aim of this paper is to present a hybrid approach to accurate quantification
      of vascular structures from magnetic resonance angiography (MRA) images using
      level set methods and deformable geometric models constructed with 3-D Delaunay
      triangulation. Multiple scale filtering based on the analysis of local intensity
      structure using the Hessian matrix is used to effectively enhance vessel
      structures with various diameters. The level set method is then applied to
      automatically segment vessels enhanced by the filtering with a speed function
      derived from enhanced MRA images. Since the goal of this paper is to obtain
      highly accurate vessel borders, suitable for use in fluid flow simulations, in a
      subsequent step, the vessel surface determined by the level set method is
      triangulated using 3-D Delaunay triangulation and the resulting surface is used
      as a parametric deformable model. Energy minimization is then performed within a
      variational setting with a first-order internal energy; the external energy is
      derived from 3-D image gradients. Using the proposed method, vessels are
      accurately segmented from MRA data.

PMID- 15493694
TI  - High-resolution functional vascular assessment with ultrasound.
AB  - In order to improve the resolution of contrast-assisted imaging systems, we have
      created a high-frequency destruction/contrast replenishment imaging system with a
      spatial resolution of 160 microm x 160 microm. The system utilizes a 1-MHz
      cylindrically focused transducer for destruction and a 25-MHz spherically focused
      transducer for pulse/echo imaging. Speckle tracking and a clutter filter are
      applied across frames to remove the challenging physiologic motion artifacts that
      are obtained when imaging with a mechanically scanned transducer. Using a new
      estimation technique, flow constants proportional to absolute flow rate were
      estimated from B-mode time-intensity curves (TICs). The in vitro results indicate
      a correlation between the actual flow velocity and the estimated rate constant.
      In vivo images are presented showing blood perfusion in the ciliary processes and
      iris of the rabbit eye. The regions of interest (ROIs) from the ciliary processes
      yielded slower perfusion compared with the iris, as expected from vascular casts
      of the microcirculation in this region. Potential applications of this system
      include high-resolution perfusion assessment in small animals.

PMID- 15493695
TI  - Determining correspondence in 3-D MR brain images using attribute vectors as
      morphological signatures of voxels.
AB  - Finding point correspondence in anatomical images is a key step in shape analysis
      and deformable registration. This paper proposes an automatic correspondence
      detection algorithm for intramodality MR brain images of different subjects using
      wavelet-based attribute vectors (WAVs) defined on every image voxel. The
      attribute vector (AV) is extracted from the wavelet subimages and reflects the
      image structure in a large neighborhood around the respective voxel in a
      multiscale fashion. It plays the role of a morphological signature for each
      voxel, and our goal is, therefore, to make it distinctive of the respective
      voxel. Correspondence is then determined from similarities of AVs. By
      incorporating the prior knowledge of the spatial relationship among voxels, the
      ability of the proposed algorithm to find anatomical correspondence is further
      improved. Experiments with MR images of human brains show that the algorithm
      performs similarly to experts, even for complex cortical structures.

PMID- 15493696
TI  - Computer-aided diagnosis of solid breast nodules: use of an artificial neural
      network based on multiple sonographic features.
AB  - A computer-aided diagnosis (CAD) algorithm identifying breast nodule malignancy
      using multiple ultrasonography (US) features and artificial neural network (ANN)
      classifier was developed from a database of 584 histologically confirmed cases
      containing 300 benign and 284 malignant breast nodules. The features determining
      whether a breast nodule is benign or malignant were extracted from US images
      through digital image processing with a relatively simple segmentation algorithm
      applied to the manually preselected region of interest. An ANN then distinguished
      malignant nodules in US images based on five morphological features representing
      the shape, edge characteristics, and darkness of a nodule. The structure of ANN
      was selected using k-fold cross-validation method with k = 10. The ANN trained
      with randomly selected half of breast nodule images showed the normalized area
      under the receiver operating characteristic curve of 0.95. With the trained ANN,
      53.3% of biopsies on benign nodules can be avoided with 99.3% sensitivity.
      Performance of the developed classifier was reexamined with new US mass images in
      the generalized patient population of total 266 (167 benign and 99 malignant)
      cases. The developed CAD algorithm has the potential to increase the specificity
      of US for characterization of breast lesions.

PMID- 15493697
TI  - Atlas-based segmentation of pathological MR brain images using a model of lesion
      growth.
AB  - We propose a method for brain atlas deformation in the presence of large space
      occupying tumors, based on an a priori model of lesion growth that assumes radial
      expansion of the lesion from its starting point. Our approach involves three
      steps. First, an affine registration brings the atlas and the patient into global
      correspondence. Then, the seeding of a synthetic tumor into the brain atlas
      provides a template for the lesion. The last step is the deformation of the
      seeded atlas, combining a method derived from optical flow principles and a model
      of lesion growth. Results show that a good registration is performed and that the
      method can be applied to automatic segmentation of structures and substructures
      in brains with gross deformation, with important medical applications in
      neurosurgery, radiosurgery, and radiotherapy.

PMID- 15493698
TI  - Predictive cardiac motion modeling and correction with partial least squares
      regression.
AB  - Respiratory-induced cardiac deformation is a major problem for high-resolution
      cardiac imaging. This paper presents a new technique for predictive cardiac
      motion modeling and correction, which uses partial least squares regression to
      extract intrinsic relationships between three-dimensional (3-D) cardiac
      deformation due to respiration and multiple one-dimensional real-time measurable
      surface intensity traces at chest or abdomen. Despite the fact that these surface
      intensity traces can be strongly coupled with each other but poorly correlated
      with respiratory-induced cardiac deformation, we demonstrate how they can be used
      to accurately predict cardiac motion through the extraction of latent variables
      of both the input and output of the model. The proposed method allows cross
      modality reconstruction of patient specific models for dense motion field
      prediction, which after initial modeling can be used for real-time prospective
      motion tracking or correction. Detailed numerical issues related to the technique
      are discussed and the effectiveness of the motion and deformation modeling is
      validated with 3-D magnetic resonance data sets acquired from ten asymptomatic
      subjects covering the entire respiratory range.

PMID- 15493699
TI  - A modeling approach for burn scar assessment using natural features and elastic
      property.
AB  - A modeling approach is presented for quantitative burn scar assessment. Emphases
      are given to: 1) constructing a finite-element model from natural image features
      with an adaptive mesh and 2) quantifying the Young's modulus of scars using the
      finite-element model and regularization method. A set of natural point features
      is extracted from the images of burn patients. A Delaunay triangle mesh is then
      generated that adapts to the point features. A three-dimensional finite-element
      model is built on top of the mesh with the aid of range images providing the
      depth information. The Young's modulus of scars is quantified with a simplified
      regularization functional, assuming that the knowledge of the scar's geometry is
      available. The consistency between the relative elasticity index and the
      physician's rating based on the Vancouver scale (a relative scale used to rate
      burn scars) indicates that the proposed modeling approach has high potential for
      image-based quantitative burn scar assessment.

PMID- 15493700
TI  - Wingspread Declaration on School Connections.

PMID- 15493701
TI  - Why we harass nerds and freaks: a formal theory of student culture and norms.

PMID- 15493702
TI  - The importance of bonding to school for healthy development: findings from the
      Social Development Research Group.

PMID- 15493703
TI  - Relationships matter: linking teacher support to student engagement and
      achievement.

PMID- 15493704
TI  - Measuring student relationships to school: attachment, bonding, connectedness,
      and engagement.

PMID- 15493705
TI  - School connectedness and the transition into and out of health-risk behavior
      among adolescents: a comparison of social belonging and teacher support.

PMID- 15493706
TI  - The interface of school climate and school connectedness and relationships with
      aggression and victimization.

PMID- 15493708
TI  - We are more alike than we are different.

PMID- 15493707
TI  - Health care continuation available under COBRA.

PMID- 15493709
TI  - Influenza immunization among health care workers.

PMID- 15493710
TI  - [The proportion of drivers with alcohol in blood in common traffic].
AB  - The negative influence of alcohol on the ability of drivers for safe driving of
      motor vehicles is generally known. In order to determine the relative risk of
      traffic accident (especially with life consequences) in drivers after alcohol
      intake in comparison with those who are sober, the occurrence of such drivers in
      a common traffic is necessary. The authors controlled at random order the
      presence of alcohol in breath of 6180 drivers of passenger cars in the year 2001.
      The examinations were negative in 5839 cases, 150 offences were executed at the
      spot (as the breath test indicated level below 0.3g/l), 36 drivers refused blood
      sampling, which on the other hand was made in 155 drivers. The concentration o
      0.3g/l and more was established in 145 drivers, i.e. 2.35% of all controlled
      individuals.

PMID- 15493711
TI  - [Determination of AB0 blood group system from degraded blood stains on
      serological and molecular genetic level].
AB  - The AB0 blood group system typing remains one of the basic laboratory tasks in a
      forensic practice. However, problems arise when the analysed samples are
      seriously degraded. We took blood samples from six volunteers (three men, three
      women) and made blood stains on pieces of sterile cotton cloth. Blood stains were
      incubated at three different temperatures (22 degrees C, 37 degrees C, 56 degrees
      C) for various periods of time (1 day, 1 week, 14 days, 1 month, 3 months, 6
      months, 1 year). For blood stains degraded at 22 degrees C we also analysed the
      samples after 3.5 hours of incubation. Moreover, we tried to determine the AB0
      blood group system after thermal degradation at high temperature, accurately at
      200 degrees C for 10 min. For the AB0 blood group system typing a Polymerase
      Chain Reaction method was used to amplify glycosyltransferase gene, when DNA had
      been isolated from artificially created blood stains, followed by their
      subsequent artificial thermal degradation. For serological AB0 typing the mixed
      agglutination and the Therkelsen method were used. The DNA analysis seemed to
      solve problems with seriously degraded blood stains but we found out that
      classical serological methods were even better in some cases.

PMID- 15493713
TI  - Fetal membrane inflammatory cytokines: a switching mechanism between the preterm
      premature rupture of the membranes and preterm labor pathways.
AB  - Inflammatory cytokines are involved in both preterm labor and preterm premature
      of the membranes pathways; however, the interaction between TNF-alpha and its
      receptors may dictate the clinical outcome of pregnancy.

PMID- 15493714
TI  - Preeclampsia--abnormal uterine artery Doppler is related to recurrence of
      symptoms during the next pregnancy.
AB  - BACKGROUND: Impaired trophoblast invasion is suggested as the main cause of
      reduced placental perfusion, which results in fetal growth restriction and
      preeclampsia. Immunological response against the invading tissue has been given
      as the explanation. Preeclampsia frequently recurs during the next pregnancy.
      Doppler ultrasound can predict increased vascular impedance in the uteroplacental
      circulation. Whether signs of increased vascular resistance in pregnancies
      complicated by preeclampsia are predictive of recurrence during the next
      pregnancy is unknown. METHODS AND MATERIAL: Uterine artery Doppler was performed
      in 570 pregnant women with preeclampsia. Of these, 139 became pregnant again. The
      uterine artery Doppler results during the first pregnancy were related to
      symptoms of preeclampsia in the succeeding pregnancy. RESULTS: Preeclampsia
      developed again in 43 of the 139 women. Pregnancies with signs of increased
      uterine artery vascular impedance during the first pregnancy were 3.4 times more
      likely to develop preeclampsia again (CI 1.58-7.6). Similar results for a small
      for gestational age newborn were 9.7 (CI 1.1-90). CONCLUSION: Increased uterine
      artery vascular impedance in pregnancies complicated by preeclampsia increases
      the likelihood of recurrence and growth restriction during the next pregnancy.
      The Doppler information gathered during the first pregnancy might thus select
      cases for special surveillance and possibly prophylactic anti-platelet treatment
      in the next pregnancy.

PMID- 15493712
TI  - [B0 aberrant genotype of AB0 blood group system].
AB  - The AB0 blood group system typing remains one of the basic laboratory tasks in a
      forensic practice. However, problems arise when the analysed samples are
      seriously degraded. The DNA analysis promised to solve this but an unexpected
      complication was encountered. For the AB0 blood group system typing a Polymerase
      Chain Reaction method was used to amplify glycosyltransferase gene, when DNA had
      been isolated from artificially created blood stains, followed by their
      subsequent artificial thermal degradation. In the B0 genotype an aberrant
      genotype was suprisingly found and its structure was confirmed by sequencing.
      This meant that a newly formed B00 (not the original BO) genotype was present.
      Such a finding, to our best knowledge, had not been observed yet and we were
      unable to find any references in the professional literature. The explanation of
      this result thus remains unclear.

PMID- 15493715
TI  - Mother-to-infant vertical transmission of transfusion transmitted virus in South
      China.
AB  - A nested PCR was used to detect TTV DNA in serum from 490 mother-infant pairs to
      determine the rate of vertical transmission of TTV in Guangzhou City, P.R. China.
      TTV DNA was positive in 87 mothers and 12 of their babies, giving a prevalence of
      17.8% in pregnant women and a mother-to-child transmission rate of 13.8%. In
      eight mother-infant pairs, TTV DNA nucleotide sequences from the mothers and
      their corresponding infants were identical. The homology of Guangzhou TTV and
      Japanese TTV ranged from 85.3%-98.2% at nucleotide level. TTV infection is common
      in pregnant women in South China and vertical transmission can occur. Guangzhou's
      and Japanese TTV isolates belong to the same genotype.

PMID- 15493716
TI  - Evaluation of second trimester maternal serum screening for Down's Syndrome using
      the Spiegelhalter-Knill-Jones (S-KJ) approach.
AB  - AIMS: Risk estimation for Down's syndrome in antenatal serum screening with
      maternal age and multiple serum biomarkers is usually complicated and
      computationally intensive. We have developed a simple scoring system using the
      Spiegelhalter-Knill-Jones approach, which was based on Bayesian theorem and the
      logistic regression model. METHODS: A prospective data set with 3842 singleton
      pregnancies including 6 affected pregnancies served as "trained data". Maternal
      age, maternal serum alpha-fetoprotein and human chorionic gonadotrophin levels of
      each pregnant woman were adopted as the predictors to establish the scoring model
      using the S-KJ approach. Model validation was undertaken using a receiver
      operating characteristics (ROC) curve with another 3050 singleton pregnancies
      including 4 affected pregnancies ("validated data"). RESULTS: For the trained
      data the sensitivity and specificity of the scoring system at cut-off value of
      1:250 was 66.7% and 92.6%, respectively. For the validated data the sensitivity
      and specificity at the same cut-off point was 75% and 92.2%, respectively. The
      area under the ROC curve of the trained and validated data was 76.96% (95% CI:
      51.80-100%), and 94.07% (95% CI: 84.47-100%), respectively. CONCLUSIONS: The S-KJ
      scoring system has been demonstrated to be a simple, and efficient method for the
      risk estimation of Down's syndrome. This system can be applied to other antenatal
      serum screening systems.

PMID- 15493717
TI  - Beta2-adrenergic receptor gene polymorphisms and pregnancy outcome.
AB  - AIMS: The association between alleles at two loci of the polymorphic beta2
      adrenergic receptor (beta2AR) gene and pregnancy outcome was determined. METHODS:
      In a case-control study, buccal swabs obtained from 159 mother-infant pairs after
      a preterm or term birth were analyzed by gene amplification and endonuclease
      digestion for polymorphisms at codons 16 and 27 of the beta2AR gene. RESULTS:
      Homozygosity for allele A at codon 16 (Arg-16) occurred in 26 (20.5%) of 127
      mothers with a term birth and in none of the mothers who had a spontaneous
      preterm birth (p=0.002). Conversely, 24 of 32 (75.0%) mothers with a spontaneous
      preterm birth, as compared to 58 of 127 (45.7%) mothers with term births, were
      Arg-16/ allele G (Gly-16) heterozygotes (p=0.003). There was no relation between
      pregnancy outcome and infant genotype at codon 16 or maternal or infant genotypes
      at codon 27. The alleles at codon 16 and 27 were in linkage disequilibrium and
      the combinations of Arg-16-Gln-27 homozygosity (p=0.04) and Arg-16/Gly-16-Gln
      homozygous (p=0.01) were associated with a decreased and increased rate of
      spontaneous preterm birth, respectively. CONCLUSION: At codon 16 of the beta2-AR
      gene, maternal Arg-16 homozygosity protects against, and Gly-16 predisposes to
      spontaneous preterm birth.

PMID- 15493719
TI  - Comparison of intrapartum fetal heart rate tracings in patients with neonatal
      seizures vs. no seizures: what are the differences?
AB  - OBJECTIVE: To determine which intrapartum fetal heart rate parameters in the
      presence of severe neonatal acidosis (pH < 7.0) appropriately predicts the
      development of neonatal seizures in the context of hypoxic ischemic
      encephalopathy (HIE). METHODS: The intrapartum fetal heart rate tracings of 25
      neonates who developed neonatal seizures secondary to HIE were compared with 25
      matched neonates with similar pH and gestational age who did not develop
      seizures. All patients had at least 2 hours of intrapartum fetal heart rate
      patterns available for review. We compared the fetal heart rate parameters of
      prolonged deceleration, variable and late decelerations, variability,
      accelerations, fetal heart rate baseline and duration of the fetal heart rate
      abnormality. Comparison between the groups was done using chi-square for nominal
      data and student t-tests for continuous data. RESULTS: Neonates with seizures 2
      degrees HIE had a significantly longer duration of abnormal fetal heart rate
      patterns (72 +/- 12 minutes vs 48 +/- 12 minutes, p < 0.001). DISCUSSION: This
      study demonstrated that in the setting of neonatal acidosis the development of
      seizures is related to the period of stress (duration of the abnormal fetal heart
      rate pattern).

PMID- 15493718
TI  - Maternal and fetal insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and IGF BP
      3, and their relationship to fetal acidosis at delivery.
AB  - OBJECTIVE: To investigate the relationship between levels of insulin-like growth
      factors 1 and 2 (IGF-1, IGF-2), and insulin-like growth factor binding protein 3
      (IGFBP-3) in antenatal maternal serum and in fetal cord blood at delivery.
      METHODS: Prospective cohort study of 1650 low-risk Caucasian women in a
      University teaching hospital in London. Statistical analysis was performed using
      commercial software (SPSS for Windows, version 6.1, SPSS, Chicago, Illinois,
      USA), with p<0.05 as significant. Maternal IGF 1, IGF 2 and IGF BP-3 were
      assessed on maternal blood at booking and in fetal blood by cord blood analysis
      at delivery. Cord pH was also recorded. RESULTS: There was no significant
      correlation between maternal IGF-1, IGF-2, or IGFBP-3 levels and fetal acidosis.
      However, a significant correlation does exist between cord IGF-1 levels and fetal
      acidosis. CONCLUSION: Fetal cord IGF-1 has a significant correlation with fetal
      acidosis at delivery.

PMID- 15493720
TI  - Computerized cardiotocography parameters in pregnant women affected by
      pregestational diabetes mellitus.
AB  - AIM: To evaluate whether computerized CTG (cCTG) is a reliable method of
      predicting neonatal outcome in pregnancies complicated by pregestational diabetes
      at term. PATIENTS AND METHODS: We considered 27 pregnant women affected by
      pregestational diabetes and 46 normal pregnancies as controls that fulfilled the
      following criteria: singleton, Caucasian, euglycemic pregnancies at term (>37
      weeks gestational age). All women delivered by cesarean section (CS), with an
      antepartum cCTG performed within one hour before the CS and an UBGA available at
      birth. No patient was in labor during FHR monitoring. RESULTS: Among cCTG
      parameters, accelerations 15 bpm, HV min, HV ms and STV were significantly lower
      in comparison to controls. We observed that in the diabetic pregnant women the
      parameter STV was not able to predict or to linearly regress with the most
      important UBGA parameters: pH and pCO2. Contrarily, in normal pregnancies, the
      STV linearly regressed with both the pH (p < 0.03) and pCO2 (p<0.04).
      CONCLUSIONS: Computerized FHR criteria may not be applicable to fetuses in
      pregestational diabetic pregnancies at term. Therefore some criteria should
      perhaps be modified for a correct interpretation of cCTG in these pregnancies.

PMID- 15493721
TI  - The effect of processing and cryopreservation on nucleated umbilical cord blood
      cells.
AB  - Recovery of nucleated cord blood cells after storage in liquid nitrogen was
      evaluated. Red cells were depleted using Ficoll-Paque or Puregene red cell lyses.
      Freeze Medium contained 10% dimethylsulfoxide and 20% serum for cryoprotection.
      Recovery of the original cell population remaining serviceable for fluorescence
      activated cell sorting (FACS) was 12 +/- 10% (average +/- standard deviation),
      with a range of 1% to 55%. Viability measured by FACS analysis after freezing was
      significantly lower than that of the same specimens prior to freezing, 62 +/- 20%
      compared to 91+/-11% (p<0.001). Percentage CD45+34+ cells were the same for fresh
      and frozen cells. Gestational age at which specimens were collected had no effect
      on the percent cells carrying the CD45+34+ markers. We conclude that better
      cryoprotective supplements are needed to insure consistent high recovery of
      viable nucleated umbilical cord blood cells after preservation in liquid
      nitrogen.

PMID- 15493722
TI  - Etiology of cerebral palsy.
AB  - AIMS: To register the prevalence of cerebral palsy (CP) and determine etiological
      factors for the condition. METHODS: Population based study with registration of
      CP-cases in children born during the 30-year period 1970-99. Cases with
      postneonatal etiology were excluded. RESULTS: 166 CP-cases were registered among
      70 824 children, a prevalence of 2.3 per 1000 live born infants. The prevalence
      did not change significantly during the period. 66 (40%) were low birthweight
      infants (LBWIs; <2500 g), and 100 (60%) normal birthweight infants (NBWIs; > or =
      2500 g). The origin was classified as prenatal in 37 (22%), perinatal/neonatal in
      78 (47%) and unclassifiable in 51 (31 %). In LBWIs 39/66 (59%) had a
      perinatal/neonatal etiology, most frequently intra- or periventricular
      hemorrhages (IVH/PVH) and/or periventricular leukomalacia (PVL) or cerebral
      infarctions (CI) (17; 44%). In NBWIs 39/100 (39%) had a perinatal etiology, most
      frequently hypoxic-ischemic encephalopathy (HIE) (31; 79%). CONCLUSIONS: In a
      substantial percentage of CP-cases perinatal/neonatal brain injury was classified
      as the cause. Among these IVH/PVH/PVL/CI dominated in LBWIs, while HIE dominated
      in NBWIs. Our data may point to preventability of a larger part of CP than
      earlier suggested.

PMID- 15493723
TI  - Characterisation of the cytokine inflammatory response in LPS stimulated full
      term cord blood.
AB  - OBJECTIVE: Abnormal inflammatory responses are implicated in the pathogenesis of
      neonatal disease. This study aimed to describe the neonatal cytokine response
      using an in vitro model of stimulated cord blood. METHODS: Cord blood samples (n
      = 12) were incubated in RPMI 1640 medium with and without lipopolysaccharide.
      Concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8,
      interferon (IFN)-gamma and IL-10 were determined by multiplex immunoassay at 0,
      1, 3, 6 and 24 hours of incubation. The difference between stimulated and control
      response was defined as the potential secretory capacity (mean +/- S.E.M.;
      pg/million white cells). Analysis included a Kruskal-Wallis test and post-hoc
      Mann-Whitney U test. RESULTS: All cytokine capacities increased rapidly by 1 hour
      (p<0.001), except IL-10 (p=0.04). TNF-alpha peaked between 3-6 hours (1581 +/-
      377 pg/million WC), declining by 24 hours. Similarly, IFN-gamma peaked at 3
      hours. Capacity ascended throughout the incubation period for IL-6, IL-8 (631 +/-
      75 pg/million WC) and IL-10 (311 +/- 37 pg/million WC). Overall, IFN-gamma
      capacity was lowest (72 +/- 10 pg/million WC) and IL-6 capacity was greatest
      (61489 +/- 7059 pg/million WC). CONCLUSION: The neonatal inflammatory response is
      chronologically similar to that determined in adults. Immature neonatal T-cell
      function may account for the lower IFN-gamma production. These results may expand
      our knowledge of neonatal disease, etiology and management.

PMID- 15493724
TI  - Amniotic cavity cultures, blood cultures, and surface swabs in preterm infants-
      useful tools for the management of early-onset sepsis?
AB  - AIMS: To evaluate the potential benefit of amniotic fluid and amniotic/placental
      membrane cultures for the management of early-onset sepsis in preterm infants.
      METHODS: The results of amniotic cavity cultures obtained during cesarean section
      and of peripheral blood cultures and surface swabs obtained from the preterm
      infant at the time of admission were analyzed with respect to the diagnosis of
      clinical sepsis in 221 preterm infants <34 weeks of gestation. RESULTS: 136
      (61.5%) patients had negative amniotic cavity culture results or growth of
      contaminants, 56 (25.3%) had growth of Ureaplasma urealyticum, and 29 (13.1%) of
      other pathogens. The corresponding numbers for surface swabs were 82.8%, 11.6%,
      and 5.6%. A positive blood culture was found in only two neonates. Fifty-four
      patients (24.4%) had clinical early-onset sepsis. Patients with amniotic cavity
      culture results that were positive for other pathogens were significantly more
      likely to experience clinical sepsis than patients with negative culture results
      (51.7% vs 15.1%, OR 6.1, p<0.0001). Regarding surface swabs, this correlation did
      not reach statistical significance. CONCLUSION: The strong association between
      positive amniotic cavity culture results and clinical early-onset sepsis supports
      the existence of a causal relation and provides evidence for the potential value
      of amniotic and/or placental membrane sampling in the management of early-onset
      sepsis in preterm infants. Surface swabs add no additional information and hence
      should not be performed routinely.

PMID- 15493725
TI  - Massive hepatic infarction in preeclampsia: successful treatment with continuous
      hemodiafiltration and corticosteroid therapy.
AB  - Massive hepatic infarction associated with pregnancy is extremely rare, but is
      potentially fatal. A 35-year-old primigravida with mild preeclampsia developed
      acute right upper quadrant pain and marked elevation of liver enzymes at 26
      weeks' gestation. After emergent cesarean section, her condition was complicated
      by oliguric renal failure and pulmonary edema with further deterioration of
      hepatic function (aspartate transaminase 4339 IU/L; alanine transaminase 3489
      IU/L; lactate dehydrogenase 10780 IU/L). The contrast-enhanced computed
      tomography revealed non-enhancing low attenuation throughout the right lobe of
      liver, compatible with infarction. Continuous hemodiafiltration was initiated as
      renal support on postpartum day one. However, excessive fluid accumulation
      persisted, and she developed severe edema formation in both lung and systemic
      body surface. To ameliorate microvascular endothelial injury, corticosteroid
      therapy was begun on postpartum day five. Following treatment initiation, her
      renal and hepatic function showed steady improvement, accompanied by drastic
      resolution of edema formation. She was discharged five weeks postpartum with no
      additional treatment, and is without sequelae six months later. Massive hepatic
      infarction should be considered in preeclamptic patients who present acute
      abdominal pain and severe hepatic dysfunction, and continuous hemodiafiltration
      with corticosteroid therapy may improve the maternal outcome.

PMID- 15493726
TI  - The use of recombinant factor VIla in a primigravida with Glanzmann's
      thrombasthenia during delivery.
AB  - Glanzmann's thrombasthenia is an inherited hemorrhagic disorder characterized by
      a severe reduction in, or absence of, platelet aggregation in response to
      multiple physiologic agonists due to qualitative or quantitative abnormalities of
      platelet glycoprotein IIb-IIIa. Glanzmann's thrombasthenia is characterized by
      potentially major mucocutaneous bleeding and prolonged bleeding time. Platelet
      counts, platelet morphology, prothrombin, and activated thromboplastin times are
      all within normal ranges in patients with Glanzmann's thrombasthenia. Pregnancy
      and delivery are rare in Glanzmann thrombasthenia patients and have been
      associated with immediate postpartum hemorrhage. We describe the peripartum
      management of a 31-year-old primipara with Glanzmann's thrombasthenia who
      underwent spontaneous vaginal delivery. Four units of single-donor platelets, two
      units of packed red blood cells, 36 microg/kg recombinant human coagulation
      Factor VIIa (rFVIIa) were given during peripartum management.

PMID- 15493727
TI  - Potential harm from puncture resistant surgical gloves.

PMID- 15493728
TI  - Congenital diaphragmatic hernia: a major therapeutic challenge in pediatric
      critical care.

PMID- 15493729
TI  - A reappraisal of medical treatment of infantile hypertrophic pyloric stenosis.

PMID- 15493730
TI  - Prediction of outcome in infants with congenital diaphragmatic hernia or severe
      diaphragmatic eventration.
AB  - Congenital diaphragmatic hernia (CDH) and severe congenital diaphragmatic
      eventration (SDE) still have high mortality. Our aims were to identify clinical
      prognostic factors for CDH and SDE, and to determine whether the size or area of
      the proximal bilateral pulmonary arteries (PA) correlate with the clinical
      outcome. We retrospectively analyzed medical charts of 26 patients--20 with CDH
      and 6 with SDE, but no obvious other associated anomalies--admitted over a 12
      year period. We compared prenatal history, clinical manifestations, blood gas,
      and echocardiography before surgery in the survivors and the non-survivors. Ten
      patients (8 CDH, 2 SDE) died 2 to 16 days after birth, including 2 patients
      without surgery due to progressive hypoxemia. The survivors had significantly
      higher 1- and 5-min Apgar scores, higher the worst preductal arterial blood gas
      pH levels, lower oxygen indices, and lower PaCO2 (P < 0.05). The McGoon index of
      PA size measured by echocardiography was higher in survivors, but not
      statistically significant. Nakada PA index results, however, were statistically
      significant (93.07 +/- 32.02 vs. 121.07 +/- 27.08, P < 0.05) In conclusion, Apgar
      scores, preductal PaCO2, oxygen index, and pH level can predict prognosis in
      infants with CDH and SDE. The Nakada PA index, however, might be a useful
      prognostic marker for patients with CDH and SDE.

PMID- 15493731
TI  - Medical treatment with atropine sulfate for hypertrophic pyloric stenosis.
AB  - We investigated whether atropine sulfate was an effective, non-surgical method
      for treating hypertrophic pyloric stenosis (HPS). The study group consisted of 5
      patients, all of the patients presented with projectile vomiting. Hypertrophic
      pyloric stenosis was diagnosed based on abdominal sonographic findings. The age
      when symptom arose was 30.8 +/- 15.5 (mean +/- SD) days, the age upon admission
      was 43.2 +/- 9.6 days. The frequency of vomiting was 5.8 +/- 2.3 times per day.
      After admission, all patients received 10% atropine sulfate 0.01 mg/kg
      intravenous (i.v.) for 5 minutes q4H (every four hours) before each feeding.
      Formular milk was started and increased by 10 ml every feeding until full feeding
      (120 ml/kg/day) was achieved. When vomiting had ceased for a period of one day,
      i.v. atropine was changed to 0.02 mg/kg oral q4H before each feeding. The patient
      was hospitalized until full feeding was maintained for more than 2 days. Then
      oral atropine was tapered by half a dose every 2 weeks. Oral atropine was
      continued until the thickness of the pyloric muscle had normalized (< 3.5 mm).
      All five patients were successfully treated with atropine sulfate. The frequency
      of vomiting was reduced to less than two times per day (1.8 +/- 1.3 days). i.v.
      atropine was used for 6.4 +/- 3.4 days, and the oral form was used for 30 +/- 9
      days. The total number of days of atropine sulfate treatment was 36.4 +/- 9.58
      days. Full feeding was achieved at 8 +/- 5.3 days. The hospitalization was 14.6
      +/- 6.2 days. The body weight when admitted was 4000 +/- 760.8 gm and the body
      weight when discharged was 4282 +/- 901 gm. The body weight one month after
      treatment was 5210 +/- 772.5 gm. The body weight gain one month after atropine
      treatment was 1262 +/- 441.4 gm. Body weigh range on admission was from <3rd to
      25th percentile, and after one month of atropine treatment, the body weight range
      was from 10th to 75th percentile. Complications included transiently elevated
      heart rates (180-200 times/min) in two patients and facial flushing after the
      first dose of IV atropine in one patient. In conclusion, conservative treatment
      with initially IV atropine in the initial stages instead of oral atropine sulfate
      is an effective alternative to pyloromyotomy, particularly in infants with major
      concurrent disease or when parents are unwilling to let their infants undergo
      surgery. Surgical intervention is not always necessary.

PMID- 15493732
TI  - In vitro antibiotic susceptibility of lactobacilli isolated from commercial
      products containing active lactobacilli.
AB  - To survey the antibiotic susceptibility patterns of some commercially available
      Lactobacillus, we collected four commercial products that contain active
      Lactobacillus. We incubated individual product and identified these colonies by
      the methods of API50 CH test kit and RAPID ID 32A kit. Strains of Streptococcus
      thermophilus, Bifidobacterium infantis, Lactobacillus acidophilus and
      Lactobacillus casei were collected. By agar dilution method, each identified
      strain was inoculated to Brucella blood agar-MIC plates. Each plate contained one
      of the following antibiotics with different concentrations: amoxicillin,
      cephalothin, gentamicin, vancomycin, erythromycin, rifampin, tetracyclin and
      penicillin G, clindamycin, chloramphenicol, cefmetazole, metronidazole,
      ampicillin/sulbactum, cefoxtin, etc. After incubation, the growth condition of
      each Brucella blood agar-MIC plate was observed and the breakpoint of each
      antibiotic to different Lactobacillus products determined. The MICs of
      amoxicillin, ampicillin/sulbactum and penicillin-G to all identified strains were
      < or =2 microg/ml and those of vancomycin, clindamycin, erythromycin,
      metronidazole, cefmetazole and cefoxtin for L. casei were >32 microg/ml. L. casei
      was more resistant to all the testing antibiotics than the other strains.
      According to the MICs of the above antibiotics, proper active lactobacillus
      products could be chosen to prevent antibiotic-associated diarrhea in the
      pediatric field.

PMID- 15493733
TI  - Evaluation of the severity of chronic lung disease in premature infants by pulse
      oximeter.
AB  - Three parameters obtained by pulse oximeter were tested to assess the severity of
      chronic lung disease (CLD) in premature infants. The FiO2 required to keep oxygen
      saturation of 90% on pulse oximeter at rest condition was defined as FiO2Sp90.
      The value of oxygen saturation with a FiO2 of 0.21 at rest was defined as room
      air saturation. The percentage of the time duration that oxygen saturation
      exceeded 90% during the measurement with the FiO2Sp90 was defined as time
      percentage of SpO2 > or = 90% with FiO2Sp90. These parameters were monitored for
      60 minutes once weekly in very low birth weight infants for at least 4 weeks
      beginning at 34 weeks of postconceptional age. Thirty-four infants were enrolled;
      13 of them had CLD. There were totally 57 measurements in 13 infants with CLD,
      and 84 measurements in 21 infants with no CLD. Values of each parameter
      significantly correlated with the FiO2 used during the measurement; the FiO2Sp90
      had positive correlation with FiO2 (r = 0.991, p < 0.001), the room air
      saturation and time percentage of SpO2 > 90% with FiO2Sp90 had negative
      correlation (r = -0.975, p < 0.001 and r = -0.668, p < 0.05, respectively). In
      the serial measurements, room air saturation improved even after the FiO2Sp90
      reached 0.21. Time-percentage of SpO2 > or = 90% with FiO2Sp90 showed increase
      with age even after the room air saturation reached over 90%. Therefore, room air
      saturation was more sensitive than FiO2Sp90, and the time-percentage of SpO2 > or
      = 90% with FiO2Sp90 was more sensitive than room air saturation in estimating the
      severity of CLD. For clinical use, FiO2Sp90 may be used as a guide for oxygen
      concentration required. Room air saturation may offer a criterion in deciding the
      need of further oxygen therapy, and time-percentage of Sp02 > or = 90% with
      FiO2Sp90 could be used to follow up the improvement of lung function, even after
      the oxygen therapy was discontinued.

PMID- 15493734
TI  - Feeding with premature or infant formula in premature infants after discharge:
      comparison of growth and nutrition status.
AB  - We designed this prospective randomized controlled study to evaluate the effects
      of premature and standard term formula on growth, nutrient intake and biochemical
      response in premature infants from hospital discharge to 6 months of corrected
      age. Premature infants with a gestational age of < or =35 weeks and a birth
      weight < or =1850 gm were assigned to receive premature infant formula (n = 19)
      or a standard term infant formula (n = 15). No differences were found between the
      two groups in weight, length, or head circumference at baseline or on follow-up.
      Infants fed premature formula had higher blood urea nitrogen and phosphorus at 3
      months of corrected age. Those on the premature formula also had higher energy
      intake at 1 month of corrected age. We suggest that premature infants, especially
      very low birth weight infants, fed preterm infant formula after discharge until 6
      months of corrected age tolerate the formula well and may benefit over those
      standard term formula.

PMID- 15493735
TI  - Acute flaccid paralysis due to myelopathy in childhood bacterial meningitis.
AB  - Spinal cord damage is a rare neurological complication of bacterial meningitis.
      From 1988 to 2001, three of 186 pediatric patients with acute bacterial
      meningitis presented with acute flaccid paralysis due to myelopathy. The disease
      onset ages and causative pathogens of the three patients were 2 days (group B
      streptococcus), 3 months (Streptococcus pneumoniae), and 13 years (Neisseria
      meningitidis), respectively. Spinal MR imaging was normal in the 13-year-old
      patient, who was left with mild residual motor weakness. Severe necrotizing
      myelitis and syringomyelia over the thoracic spinal cord were found in the other
      two younger patients. Both had severe paralysis at follow-up. All three patients
      required mechanical ventilation or vasopressor agents during antibiotic treatment
      for bacterial meningitis.

PMID- 15493736
TI  - X-linked chronic granulomatous disease: report of one case.
AB  - Chronic granulomatous disease (CGD) is an inherited dysfunction of phagocytic
      cells secondary to a defect in the respiratory burst to kill catalase-positive
      microorganisms. This leads to recurrent life-threatening bacterial and fungal
      infections. We report a 1 year-10 month-old boy with X-linked CGD who was noted
      to have recurrent suppurative lymphadenitis since one and half month old. Failure
      to thrive, lymphadenitis and generalized skin lesions with multiple scar and
      dimples were found. Immunological data of patient, his mother and father were as
      follows: PMN phagocytosis (%): 98, 88, 92 (control, >80), PMN chemotaxis: 0.6,
      1.0, 1.3 (control, >1.2), PMN bactericidal function test over a period of 2 hours
      (%): 28.1, 28.5, 84.8 (control, 82.1). PMN chemiluminescence (delta mV): 0.612,
      364.1, 1131 (control, 614.1), H202 production (ug/mL): 1.6, 7.2, 16.8 (control,
      14.1), NBT test: negative, mixed, positive (control, positive). His mother was a
      carrier. The patient expired with invasive salmonella infection before the
      availability of gamma-interferon prophylaxis.

PMID- 15493737
TI  - Miller Fisher syndrome possibly related to mycoplasma pneumoniae infection:
      report of one case.
AB  - Ophthalmoplegia, ataxia, and areflexia were first described in 1956 by Miller
      Fisher and later were referred to as symptoms of Miller Fisher syndrome (MFS).
      This syndrome shares certain features with the Guillain-Barre syndrome (GBS),
      including areflexia, cerebrospinal fluid findings and often a postinfectious
      presentation. It was believed to be a variant of GBS, but Miller Fisher syndrome
      has several key clinical features which differ from GBS. The anatomic location
      and pathogenesis of MFS continue to be a matter of debate. Our report focuses on
      a 6-year-old female patient who developed MFS following a respiratory tract
      infection with a serologically proven Mycoplasma pneumoniae infection. Although
      several neurological complications after Mycoplasma pneumoniae infection have
      been reported, subsequent MFS development has rarely been reported previously.

PMID- 15493738
TI  - Kawasaki disease presenting with lymphadenopathy and gastrointestinal hemorrhage:
      report of one case.
AB  - We report a 5-year-old boy with Kawasaki disease (KD) initially presenting with
      cervical lymphadenitis and complicated by gastrointestinal hemorrhage before the
      use of salicylates (aspirin). A previously well and fully immunized 5-year-old
      Japanese boy presented with a 5-day history of neck mass and fever. Physical
      examination showed bilateral lymphadenopathy but not nonexudative conjunctivitis,
      oral cavity changes, skin rash, or extremity changes. He was admitted with a
      diagnosis of neck lymphadenitis and treated with parenteral antibiotics. Tarry
      stool was noted on the second day of admission, before the definitive diagnosis
      of KD was made, and cimetidine was given to treat the gastrointestinal
      hemorrhage. On the fourth day of admission, he fulfilled the diagnostic criteria
      for KD (fever for 9 days plus lymphadenopathy, lip fissure, conjunctivitis, and
      skin rash). He was treated with intravenous immunoglobulin (2 g/kg/day) and
      aspirin (80 mg/kg/day), and the fever subsided promptly. Massive gastrointestinal
      bleeding occurred on the ninth day of admission and was treated with whole blood
      transfusion, after which the vital signs were stable.

PMID- 15493739
TI  - DiGeorge syndrome with truncus arteriosus: report of one case.
AB  - DiGeorge syndrome is a rare disorder characterized by a spectrum of thymic and
      parathyroid gland abnormalities, conotruncal cardiac defects, and typical facial
      dysmorphism. We report a male infant with partial DiGeorge syndrome characterized
      by truncus arteriosus, typical facial dysmorphism, hypocalcemia, lymphocytopenia
      with T-cell deficiency, and chromosome 22q11.2 deletion. Transient
      lymphocytopenia was noted for 5 days after birth and hypocalcemia was corrected
      with calcium gluconate administration. Surgical correction of the truncus
      arteriosus was performed at the age of 3 months. Unfortunately, the patient
      subsequently had an unwitnessed cardiac arrest, and despite resuscitation, died
      at the age of 4 months.

PMID- 15493741
TI  - Holoprosencephaly presenting as membranous aplasia cutis and diabetes insipidus:
      report of one case.
AB  - Membranous aplasia cutis is characterized by the presence of a cystic-like nodule
      located at the midline of the scalp, which is surrounded by a ring of long, dark
      hair, called a 'hair collar' sign; it always contributes to underlying central
      nervous malformation. Herein, we report a 2-month-old male infant who was
      admitted to our ward due to diabetes insipidus complicated with hypernatremia.
      Physical examination revealed the unique 'hair collar' sign, which is a rare
      presentation of congenital aplasia cutis. Imaging study revealed
      holoprosencephaly. Thus, the aim of this report is to remind pediatrician that in
      a neonate who has "membranous aplasia cutis" with hair collar sign, imaging
      studies, including brain sonography, computed tomography or magnetic resonance
      imaging of the brain, should be performed because of the great possibility of
      underlying central nervous system malformation.

PMID- 15493740
TI  - De Novo incontinentia pigmenti in female twins.
AB  - The cutaneous lesions of incontinentia pigmenti classically evolve in stages,
      beginning with erythematous vesicular rash and bullae, followed by verrucose
      lesions, with an eventual macular pattern of splashed or whorled
      hyperpigmentation. We describe female twins presenting with the classic form of
      cutaneous expression. Ophthalmologic examination revealed abnormal vascular
      proliferations in the peripheral retinas in twin B. Several studies have
      confirmed linkage of familial incontinentia pigmenti to chromosome Xq28, with the
      factor VIII gene in Xq28 identified as the locus for incontinentia pigmenti. Two
      hundred kilobases proximal to this locus, the gene for NEMO (NF-kappaB essential
      modulator)/IKKgamma (I kappaB kinase-gamma) has been mapped. We describe herein
      female twins with incontinentia pigmenti caused by a de novo mutation of this
      locus, as demonstrated by diagnostic polymerase chain reaction.

PMID- 15493742
TI  - [Social reforms, consequences for the patient followed in psychiatry].

PMID- 15493743
TI  - [Law project for the equality of rights and benefits for the mentally
      handicapped, how to manage?].

PMID- 15493744
TI  - [Involuntary hospitalization under question].

PMID- 15493745
TI  - [Authority and psychiatry. Should we be afraid of authority?].

PMID- 15493746
TI  - [Authority and psychiatry. Does the proper role make authority?].

PMID- 15493747
TI  - [Authority and psychiatry. Authority ... in a unit for adolescents].

PMID- 15493748
TI  - [Authority and psychiatry. The hidden faces of authority].

PMID- 15493749
TI  - [Authority and psychiatry. Authority in the nursing staff].

PMID- 15493750
TI  - [Authority and psychiatry. Education and authority].

PMID- 15493751
TI  - [Authority and psychiatry. The legitimate but controversial extension of nursing
      directors' competences. Interview by Franck Fabien].

PMID- 15493752
TI  - [Art therapy, from encounter to creation].

PMID- 15493753
TI  - [Huntington chorea and sophrology. Example of holistic care in a day
      hospitalization center].

PMID- 15493754
TI  - [Preventing insecurity, intervening in emergency situations].

PMID- 15493755
TI  - Outgoing CNO defends value of role.

PMID- 15493756
TI  - Health inequality gap must be closed.

PMID- 15493757
TI  - Is your record-keeping up to scratch?

PMID- 15493758
TI  - Ministering to spiritual needs.

PMID- 15493759
TI  - How I coped with a disability.

PMID- 15493760
TI  - NICE guidance on use of topical corticosteroids in atopic eczema.
AB  - This article examines in detail the use of topical corticosteroids in treating
      atopic eczema and the related guidance recently issued by the National Institute
      for Clinical Excellence (NICE, 2004).

PMID- 15493761
TI  - Clinical facts. Obsessive compulsive disorder.

PMID- 15493762
TI  - Improving practice in wound care for patients with dementia.

PMID- 15493763
TI  - Management of retained foreign bodies and rectal sexual trauma.
AB  - Little is written in medical or nursing literature about the incidence or
      management of rectal foreign bodies or rectal sexual trauma. Circumstantial
      evidence suggests that this rare problem is becoming more common. This article
      discusses the incidence, methods and treatment options for patients with this
      problem, and the nurse's role in ensuring they are cared for in a sensitive
      manner.

PMID- 15493764
TI  - Evaluating a project to improve care of older people in Scotland.
AB  - This is the second of two articles on an innovative pilot study in Scotland
      attempting to promote evidence-based practice in the nursing care of older people
      in a variety of residential care settings. This article documents findings from a
      qualitative process evaluation of the experiences of the eight nurse clinicians
      who participated in the pilot. The evaluation provided valuable insights into how
      future schemes might be enhanced.

PMID- 15493765
TI  - Diagnosis and treatment of malignant spinal cord compression.
AB  - Malignant spinal cord compression occurs in up to 10 per cent of people with
      cancer, and advances in treatments may increase its incidence as patients live
      longer. Nurses have an important role in all aspects of care, including early
      detection. Prompt treatment significantly improves patients' chances of avoiding
      permanent disability. However, the condition is characteristic of advanced cancer
      and therefore is in itself an indicator of poor prognosis.

PMID- 15493766
TI  - Causes and management of chronic breathlessness in adults.
AB  - Breathlessness is a common symptom associated with a variety of disorders. It is
      defined as 'an abnormal awareness or difficulty with breathing' (Bourke and
      Brewis, 1998). It can be acute or chronic. Acute breathlessness typically occurs
      within a short timeframe and may be severe. It may also be the presenting symptom
      of life-threatening disease. Chronic breathlessness develops over several months
      or years.

PMID- 15493767
TI  - Understanding the benefits of pulmonary rehabilitation.
AB  - Chronic obstructive pulmonary disease (COPD) affects 600,000 people in the UK
      (British Thoracic Society, 2001) and costs the NHS more than 800m pounds a year
      (Guest, 1999). While this data is useful for health economists and service
      providers, it does not tell us about the devastating impact COPD has on quality
      of life. The disease is commonly associated with varying degrees of
      breathlessness, cough and loss of exercise capacity. These symptoms can play a
      significant role in limiting a patient's ability to carry out simple, day-to-day
      activities.

PMID- 15493768
TI  - New guidance on long-term oxygen therapy management and delivery.
AB  - New guidance on how long-term oxygen therapy is managed and delivered will be
      implemented in 2005 (Box 1). One of its aims is to reduce the number of patients
      who receive the treatment inappropriately. The guidance comes in response to a
      Department of Health review of domiciliary oxygen therapy back in 2000. This
      looked at supply arrangements and whether patients should continue to access the
      service via GP prescription. It included the views of royal colleges, patient
      groups and oxygen suppliers.

PMID- 15493769
TI  - Decannulation of patients with long-term tracheostomies.
AB  - A tracheostomy is an artificial opening in the trachea that is held open by a
      tracheostomy tube. Inspired and expired air bypasses the mouth and nose. There is
      a range of reasons for performing a tracheostomy, including long-term mechanical
      respiratory support from, for example, a ventilator.

PMID- 15493770
TI  - How to improve your maths skills.

PMID- 15493771
TI  - Sorting the men and the boys.

PMID- 15493772
TI  - Men's health policy.

PMID- 15493773
TI  - Gender influences on men's health.

PMID- 15493774
TI  - Smoking, drinking and drug use: a privilege and a burden.

PMID- 15493775
TI  - Male central obesity.

PMID- 15493776
TI  - Older men ageing well.

PMID- 15493777
TI  - Chlamydia and male fertility.

PMID- 15493778
TI  - Men's sexual health: behaviour, infections and consequences.

PMID- 15493779
TI  - Erectile dysfunction: a need for greater awareness.
AB  - Research has led to effective treatment regimes for erectile dysfunction (ED).
      Convincing evidence links vascular risk factors (hypertension, diabetes mellitus,
      hyperlipidaemia and smoking) with ED. This association is not surprising since
      the corpus cavernosum is a modified vascular tissue. This review presents a brief
      account of the aetiology, diagnosis and treatment of ED. There is a need to raise
      awareness of this condition and to make appropriate treatment available to
      patients.

PMID- 15493780
TI  - Testicular cancer.
AB  - Testicular cancer is a rare condition, accounting for approximately 1-1.5% of all
      cancers in men. It is the most common cancer affecting men in their 20s and 30s.
      Little is known about the exact cause of this disease, although numerous risk
      factors have been recognised. Treatment of testicular cancer has been extremely
      successful, with impressive cure rates reported. This is due to the excellent
      tumour response to chemotherapy and radiotherapy, and also to the diagnosis and
      follow-up regimes.

PMID- 15493781
TI  - Understanding prostate cancer.
AB  - Prostate cancer is the second most common cancer affecting men in Europe and the
      USA. The incidence of prostate cancer has risen by 60-75% in the Western world in
      the last 15 years. One in twelve men over the age of 60 develop prostate cancer
      and this figure is expected to rise to three in twelve in the next 20 years.
      Early prostate cancer often does not cause symptoms. However, patients may
      present with lower urinary tract symptoms (LUTS) and therefore, such patients
      should be investigated. Effective treatment in the form of surgery and
      radiotherapy is availabLe for individuals with localised disease, and the
      effectiveness of different combination therapy is being assessed to improve the
      outcome further. Approximately 20% of the patients have metastatic disease on
      presentation. The mainstay of treatment for these patients is androgen ablation
      therapy; however patients on this regime eventually relapse and develop an
      androgen independent tumour. This aggressive stage of the disease carries a high
      morbidity and mortality. At present the treatment for such hormone refractory
      prostate cancer is inadequate and the desperate search for alternative forms of
      therapy continues.

PMID- 15493782
TI  - Benign prostatic hyperplasia.
AB  - Benign prostatic hyperplasia (BPH) is a common condition, which increases with
      increasing age. Although not a life-threatening condition, BPH can significantly
      affect quality of life. BPH manifests clinically with lower urinary tract
      symptoms (LUTS) and may be associated with sexual dysfunction. As many as 60% of
      men aged 60 years have some degree of clinical BPH. With the projected increases
      in the distribution of people over the age of 60, BPH isset to become an even
      greater problem in men's health.

PMID- 15493783
TI  - Cancers of the bladder.
AB  - Bladder cancer is the fifth most common malignancy in Europe and the fourth most
      common malignancy in the United States. It affects one in 4000 people and
      accounts for 5% of all diagnosed cancers. The peak incidence is in the fifth and
      seventh decade. There is a strong association between smoking and bladder cancer.
      Smokers have a fourfold higher incidence of developing bladder cancer than the
      general population. The disease has a spectrum of clinical severity varying from
      superficial bladder cancer to muscle invasive or metastatic disease which carries
      a poor prognosis. Currently the superficial form of the disease is managed by
      endoscopic resection of the tumour, often followed by the instillation into the
      bladder of cytotoxic agents. Due to the tendency of bladder cancer to recur
      repeated cystoscopies and resections are often required. Because of this, one of
      the main thrusts of research is to find a way of preventing the progression from
      superficial disease to muscle invasive and metastatic bladder cancer.

PMID- 15493784
TI  - Condom use with sex workers and abstinence behaviour among men in Nigeria.
AB  - Non-regular, non-cohabiting relationships and condom neglect are known to fuel
      the HIV/AIDS epidemic in Africa. Reproductive health needs of the men, the major
      decision-makers in this community, have been grossly neglected in this regard.
      This exploratory, community-based study assessed condom use among married men
      when with commercial sex workers (CSWs) and abstinent behaviour when their wives
      were unavailable for sex. (A CSW is one known to receive payment for sex.) Out of
      the 3,178 married respondents, 1,755 (55.2%) had ever used condoms. Of this
      number, 1,296 (73.8%) resided in urban locations while 459 (26.2%) resided in
      rural areas. Of these men, 137 had used CSWs in the six months prior to the
      study. Only 63 (46%) of these had used a condom at the last visit. Young age (<30
      years) was the only predictor of condom use when with CSWs (p=0.03). Predictors
      of abstinence behaviour when the wife was unavailable for sex included: primary
      and secondary education, young age of the wife, low occupational status and
      monogamy. National HIV/AIDS control programmes should address men's risk-taking
      behaviour, empowering women to negotiate condom use and reduce long abstinence
      periods. Continued efforts should be made to reach sex workers and to make
      condoms much more widely available, acceptable and affordable, especially in
      rural areas.

PMID- 15493785
TI  - It's a goal!: Basing a community psychiatric nursing service in a local football
      stadium.
AB  - This paper describes the development of a community mental health project in a
      local football stadium. Funded for three years by the Laureus Foundation's 'Sport
      for Good' initiative, the project provides mental health promotion and mental
      health awareness input targeted initially at young men, a group who are often
      very difficult to engage in this type work. Using group interventions and
      utilising football as a metaphor, the project helps young men address issues
      around depression, self-esteem and inclusion, and addresses the subject of
      suicide which remains the second biggest cause of death in young men in Britain.
      The paper describes the development of the project, the structure of the groups
      and the evaluation of the first two groups to complete the process. The work
      takes place in the Moss Rose stadium, home of Macclesfield Town, a team in the
      English Football League.

PMID- 15493786
TI  - NHS 'university' given an education in humility at school of hard knocks.

PMID- 15493787
TI  - Policy redesign issues. Framing the future.

PMID- 15493788
TI  - The HSJ Barometer.

PMID- 15493789
TI  - Clinical management. Where medicine meets management. Cottage industry.

PMID- 15493790
TI  - Modernisation. The road to perfection.
AB  - The Pursuing Perfection programme, piloted in four areas, lays down joint
      improvement strategies for directors of social services and NHS trusts. The
      programme dares to think what a perfect service would be like, and how it could
      be achieved. It uses the 'no needless...' formulation to eliminate risk.

PMID- 15493791
TI  - Mental health. Unlocked potential.

PMID- 15493792
TI  - HSJ people. Retain and you gain.

PMID- 15493793
TI  - Medical equipment. Helping hearts.

PMID- 15493794
TI  - Medical equipment. PET projects.

PMID- 15493795
TI  - Medical equipment. Injection of hope.

PMID- 15493796
TI  - Medical equipment. Seeing the bigger picture.

PMID- 15493797
TI  - Medical equipment. Joint efforts.

PMID- 15493798
TI  - Medical equipment. The pressure of progress.

PMID- 15493799
TI  - [We need stringent changes].

PMID- 15493800
TI  - [Career specialization].

PMID- 15493801
TI  - [European Professional Society for Nurses and Assistant Personnel].

PMID- 15493802
TI  - [Function services--intensive care nursing on the way in the ambulance].

PMID- 15493803
TI  - [Function services. The preoperative nurse's visit].

PMID- 15493804
TI  - [For the accident, the attitude of the subject].

PMID- 15493805
TI  - [Health risks in ambulatory nursing].

PMID- 15493806
TI  - [The nightmare of the cost explosion].

PMID- 15493807
TI  - [Nursing in the context of Bachelor's and Master's degrees].

PMID- 15493809
TI  - [Nursing under pressure].

PMID- 15493808
TI  - [Dimensions of professional nursing].

PMID- 15493810
TI  - [An event is not grounds for a warning].

PMID- 15493811
TI  - [Donations and company].

PMID- 15493812
TI  - [Translation and documentation. Pflege Aktuell April/2004, on "Focus
      documentation" by Sarina Schreiber].

PMID- 15493813
TI  - [The theme of MRSA and very important for us. Pflege Actuell April 2004, on
      "MRSA" by Wolfggang Reimann u.a].

PMID- 15493814
TI  - [Do not make the possible impossible. Pflege Aktuell April 2004, on "Gender
      Mainstreaming" by Gabriel Achenbach].

PMID- 15493815
TI  - Darwin's principle of divergence revisited: small steps and quantum leaps set the
      path of microbial evolution.

PMID- 15493816
TI  - Population structure of pathogenic bacteria revisited.
AB  - This minireview summarizes the historical development of bacterial population
      genetic concepts since the early 1980s. Initially multilocus enzyme
      electrophoresis was used to determine population structures but this technique is
      poorly portable between laboratories and was replaced in 1998 by multilocus
      sequence typing. Diverse population structures exist in different bacterial
      species. Two distinctive structures are described in greater detail. "Young"
      organisms, such as Yersinia pestis, have evolved or undergone a severe bottleneck
      in recent millennia and have not yet accumulated much sequence diversity.
      "genoclouds" in subgroup III Neisseria meningitidis arise because of the
      accumulation of diversity due to herd immunity, which is then purified during
      subsequent epidemic spread.

PMID- 15493817
TI  - Genetic lineages and their traits in Neisseria meningitidis.
AB  - Neisseria meningitidis is a model organism for the study of bacterial population
      biology, for genome sequencing and pathogenicity research. In the recent years,
      our group has identified a variety of markers for hypervirulent lineages of
      meningococci, which in part could be validated for typing purposes. Furthermore,
      carrier strain collections of meningococci and N. lactamica were studied by
      multilocus sequence typing, and elucidated the impressive genetic variability of
      those species. Characterisation of meningococcal carrier strains allowed to
      define the capsule null locus (cnl) of meningococci, which frequently occurs
      among carrier isolates and renders strains constitutively unencapsulated. This
      finding poses the question about the yet unclear role of the meningococcal
      polysaccharide capsule in transmission and carriage. O-acetylation of the
      meningococcal polysaccharides is another variably expressed trait in
      meningococci. We identified the genes responsible for O-acetylation of the
      serogroup C, W-135 and Y capsules, and provided the genetic basis for
      understanding the variability of O-acetylation patterns in meningococci. The oatC
      and oatWY genes proved to be the first genes identified to be responsible for O
      acetylation of polysialic acid.

PMID- 15493818
TI  - The Yersinia high-pathogenicity island (HPI): evolutionary and functional
      aspects.
AB  - The high-pathogenicity island (HPI) is a genomic island essential for the mouse
      virulence phenotype in Yersinia and indispensable for pathogenicity of Yersinia
      and certain pathotypes of Escherichia coli. In contrast to most genomic islands,
      the HPI is a functional island widely disseminated among members of the family of
      Enterobacteriaceae. The HPI-encoded phage P4-like integrase together with
      excisionase and recombination sites make up the genetic mobility module of the
      island, while the siderophore yersiniabactin biosynthesis and uptake system
      comprises its functional part with respect to fitness and pathogenicity. The HPI
      integrase promotes integration of the island into attB sites represented by three
      to four asn tDNAs in Yersinia pestis and E. coli. An additional enzyme,
      excisionase, is essential for efficient excision of the HPI from the initial site
      of integration. Furthermore a unique type of HPI has been characterized in the E.
      coli strain ECOR31 carrying a functional conjugative mating pair formation (Mpf)
      and a DNA-processing system, both of which are characteristic of integrative and
      conjugative elements (ICE). A model of conjugative transfer for the dissemination
      of HPIs is proposed in which the excised HPI is mobilized to a new recipient
      either trapped by a transmissive asn tDNA-carrying plasmid or autonomously as an
      ICE named ICEEcl.

PMID- 15493819
TI  - Evolution of pathogenicity islands of Salmonella enterica.
AB  - Virulence genes located on pathogenicity islands play a crucial role in the
      pathogenesis of Salmonella enterica infections. Salmonella pathogenicity islands
      (SPI) contribute to host cell invasion and intracellular pathogenesis. At
      present, 12 SPI have been described. Although size, structure and function of
      these SPI, as well as the distribution in Salmonella subspecies and serovars can
      be markedly different, several common motifs are present among SPI. In this
      review, the characteristics of SPI are described with focus on the evolution of
      these genetic elements.

PMID- 15493820
TI  - Impact of the locus of enterocyte effacement pathogenicity island on the
      evolution of pathogenic Escherichia coli.
AB  - This review summarizes our current knowledge and models of appearance and
      dissemination of the locus of enterocyte effacement (LEE) within Escherichia coli
      phylogenetic lineages. The LEE is a pathogenicity island (PAI) required for
      attaching and effacing (A/E) lesion formation induced on epithelial cells of
      humans and animals by enteropathogenic and numerous enterohemorrhagic E. coli
      strains as well as other related bacteria. The LEE encodes a type III secretion
      system, an adhesin (intimin) responsible for the intimate attachment of the
      bacteria to the cell and a number of secreted proteins involved in signal
      transduction events. It has been shown that the LEE varies in size from 36 to 111
      kb, depending on what E. coli lineages carrying that PAI. Three tRNA genes are
      known as LEE integration sites selC, pheU and pheV, the latter two are identical
      in sequence. Beneath its functional role, intimin is considered a phylogenetic
      marker of the LEE. Currently, 14 different intimin types have been described,
      designated alpha through ksi. Beta intimin-carrying LEEs moved within certain E.
      coli lineages from the pheU tRNA gene into the pheV tRNA gene. Moreover, as a
      result of the typing of multiple LEE core regions, the appearance of two
      different LEE cores indicates an import of the LEE within E. coli at least two
      times.

PMID- 15493821
TI  - Shiga toxin-encoding bacteriophages--genomes in motion.
AB  - Shiga toxins (Stx) represent a group of bacterial toxins that are involved in
      human and animal disease. Stx are mainly produced by Escherichia coli isolated
      from human and non-human sources, Shigella dysenteriae type 1, and sporadically,
      by Citrobacter freundii, Enterobacter cloacae and Shigella flexneri. The genes
      encoding Stx are encoded in the genome of heterogeneous lambdoid prophages (Stx
      converting bacteriophages; Stx-phages). They are located in a similar position in
      the late region of the prophage genome and stx is under control of phage genes.
      Therefore, induction of Stx-converting prophages triggers increased production of
      Stx. Following induction, Stx-phages can infect other bacteria in vivo and in
      vitro. Stx-phages may be considered to represent highly mobile genetic elements
      that play an important role in the expression of Stx, in horizontal gene
      transfer, and hence in genome diversification.

PMID- 15493822
TI  - Pseudomonas aeruginosa and Burkholderia cepacia in cystic fibrosis: genome
      evolution, interactions and adaptation.
AB  - The Gram-negative bacteria Pseudomonas aeruginosa and Burkholderia cepacia are
      opportunistic human pathogens that are responsible for severe nosocomial
      infections in immunocompromised patients and are the major pathogens in cystic
      fibrosis (CF). The two bacteria not only inhabit the same environmental niches
      but can also form mixed biofilms in the lungs of CF patients. Hence, it appears
      very likely that the two organisms are capable of interacting with each other.
      Work of the past few years has shown that both bacteria utilize quorum-sensing
      systems, which rely on N-acyl-homoserine lactone signal molecules, to control the
      expression of virulence factors and biofilm development. Most importantly,
      evidence has been presented that these signal molecules also serve as a universal
      language for communication between the two organisms. Moreover, analyses of the
      diversity in P. aeruginosa revealed the presence of genome islands that contain
      genes that are highly homologous to genes identified in strains of Burkholderia
      sp. This finding suggests that there is a frequent exchange of genetic material
      between the two organisms.

PMID- 15493823
TI  - Helicobacter pylori: recombination, population structure and human migrations.
AB  - Helicobacter pylori shows extensive genetic diversity and variability due to
      frequent intraspecific recombination during mixed infection. In the last years,
      modern genetic and genomic technology as well as cutting-edge population genetic
      analysis have been used to investigate the population structure and genetic
      variability of this pathogen. This review article summarizes recent developments
      in this rapidly moving field.

PMID- 15493824
TI  - Cryptic plasmids in Helicobacter pylori: putative functions in conjugative
      transfer and microcin production.

PMID- 15493825
TI  - Preference, adaptation and survival of Mycoplasma pneumoniae subtypes in an
      animal model.
AB  - The interaction between Mycoplasma pneumoniae and its natural host, humans,
      cannot be studied directly for obvious reasons. Therefore, we used guinea pigs
      instead, which had been recently introduced as an acceptable alternative host
      organism. The following experimental approaches were taken to study the pathogen
      host relationship: characterization and subtyping of M. pneumoniae strains
      isolated from human patients, infection of guinea pigs with selected M.
      pneumoniae strains, and analysis of adaptation, preference and survival of
      individual strains in guinea pigs under competitive conditions. The results of
      our study indicated that the species M. pneumoniae is genetically very
      homogeneous. From 115 independently isolated strains two subtypes and one variant
      were found. The subtypes differed significantly in the amino acid composition of
      the P1 protein, the main adhesin of M. pneumoniae, while the variant showed only
      minor amino acid exchanges. Infection of guinea pigs indicated differences
      between the subtypes and the variant in their ability to colonize and survive in
      the animal. Preinfection of the host with a certain subtype or variant caused a
      subtype-specific immunity and had a strong influence on the type of surviving
      bacteria in superinfection experiments. The results of these studies explain the
      shift of subtypes frequently observed in epidemic outbreaks of M. pneumoniae
      infection appearing in intervals of 3-7 years.

PMID- 15493826
TI  - Mosaic genes and mosaic chromosomes-genomic variation in Streptococcus
      pneumoniae.
AB  - The genome sequences of two strains of Streptococcus pneumoniae, one of the major
      human pathogens, are currently available: that of the nonencapsulated laboratory
      strain R6, the origin of which dates back to the early 20th century, and of the
      serotype 4 TIGR strain isolated recently. The two genomes are not only different
      in size (2 versus 2.16 Mb) but differ also by approximately 10% of their genes,
      many of which being organized in large clusters. Their strain-specific genes and
      gene clusters are described here. The R6 genome contains 69 kb organized in six
      large regions that are absent from the TIGR strain, which in turn contains an
      extra 157kb in twelve clusters compared to R6. In addition, the TIGR strain
      contains 13 clusters of 4 kb and larger that are not shared by a variety of
      genetically different S. pneumoniae strains. Many regions bear signs of gene
      transfer events such as the presence of insertion sequences, transposable
      elements, and putative site-specific integrases/recombinases. Three strain
      specific regions are devoted to genes encoding proteins with the cell wall anchor
      motif LPXTG which are important for the interaction with host cells and appear to
      be highly variable, similar to cell wall-associated choline-binding proteins.

PMID- 15493827
TI  - Surface proteins of Streptococcus agalactiae and horizontal gene transfer.
AB  - Streptococcus agalactiae is responsible for serious infectious diseases in
      neonates, immuno-compromised adult patients and causes bovine mastitis in animal
      hosts. Genome sequencing projects revealed strong indications for horizontal gene
      transfer events leading to virulence acquisition and genetic diversity in this
      species. Bacterial surface proteins establish the first contact with host tissues
      and represent interesting targets for the exchange of virulence properties among
      different streptococci. This review will focus on horizontal gene transfer events
      in characterized S. agalactiae surface proteins, mobile genetic elements adjacent
      to the corresponding genes and will discuss potential mechanisms of transfer.

PMID- 15493828
TI  - The intracellular status of Streptococcus pyogenes: role of extracellular matrix
      binding proteins and their regulation.
AB  - Streptococcus pyogenes (group A streptococci, GAS) is an important and
      exclusively human pathogen. Adherence to and internalization into host cells
      significantly contributes to the pathogenesis of GAS infections. The adherence
      mechanism is a two-step process in which host extracellular matrix (ECM) proteins
      act as prime targets. GAS may express more than a dozen different microbial
      surface components recognizing adhesive matrix molecules (MSCRAMMs) that attach
      to fibronectin or collagen. One of them, protein F1/SfbI binds fibronectin and
      mediates adherence of GAS to host cells. Bound fibronectin acts as a bridging
      molecule towards host cell integrins, which in turn initialize the uptake process
      that leads to GAS internalization. In their safe intracellular niche GAS can
      persist protected from antibiotics and host defense, a scenario currently
      discussed in the context of treatment failure, asymptomatic GAS carriers and
      recurrent GAS infections. Patients with such low grade infections represent the
      main GAS reservoir from which the bacteria are spread in the general population.
      Due to their important function, expression of GAS MSCRAMMs is under control of
      several "stand alone" transcriptional regulators and two-component signal
      transduction systems. Several regulator genes are organized together with MSCRAMM
      genes on one of two potential pathogenicity islands, act together in a growth
      phase-dependent regulatory network and are expressed in a strain-specific manner.
      A detailed understanding of these mechanisms is crucial, since interference with
      MSCRAMM function alone or in conjunction with specific manipulations of
      regulators is an attractive goal for novel anti-infective strategies.

PMID- 15493829
TI  - Bacterial evasion of innate host defenses--the Staphylococcus aureus lesson.
AB  - Bacterial pathogens such as Staphylococcus aureus use highly efficient mechanisms
      to evade recognition and elimination by the innate immune system. S. aureus
      produces sophisticated anti-inflammatory molecules and it employs several
      mechanisms protecting the bacteria against host cationic antimicrobial molecules
      such as defensin-like peptides and bacteriolytic enzymes such as lysozyme. Cell
      wall teichoic acids and lipoteichoic acids, complex Gram-positive surface
      polymers, and modified membrane lipids such as lysylphosphatidylglycerol are
      crucial in defensin resistance and other important aspects of staphylococcal
      virulence such as nasal colonization and biofilm formation on biomaterials.
      Certain S. aureus genes conferring escape from innate host defenses are conserved
      in many human pathogens suggesting that the underlying mechanisms are of general
      significance in bacterial virulence.

PMID- 15493830
TI  - Regulatory and genomic plasticity of Staphylococcus aureus during persistent
      colonization and infection.
AB  - The major human pathogen Staphylococcus aureus asymptomatically colonizes the
      anterior nares of humans, but also causes a wide spectrum of diseases including
      chronic infections such as device-related infections and lung infections in
      patients with cystic fibrosis (CF). Successful adaptation of the pathogen to the
      human host is achieved by regulatory mechanisms in the short term and by
      inheritable shifts in the population over the long term. From direct transcript
      analysis during infection we deduced that S. aureus is provided with regulatory
      circuits different than those characterized in vitro. The major virulence
      regulator agr is not active during chronic infections and agr mutants are
      frequently isolated from these specimens. Consequently no agr-dependent
      interference between S. aureus strains was observed during lung infection in CF.
      The regulator sae seems to be a key factor in the regulatory network controlling
      gene expression in vivo. S. aureus evolved over the millennia by adapting to the
      nasal environment and therefore evolutionary changes that can be witnessed over
      the short term are rare in colonizing strains. In contrast, during chronic
      infection in CF strong selective pressure is exerted on the pathogen, leading to
      discernable variations in the clonal lineages. Phage mobilization contributes
      significantly to genome alteration in S. aureus during infection.

PMID- 15493831
TI  - Mechanisms of biofilm formation in Staphylococcus epidermidis and Staphylococcus
      aureus: functional molecules, regulatory circuits, and adaptive responses.
AB  - Biomaterial-associated infections, most frequently caused by Staphylococcus
      epidermidis and Staphylococcus aureus, are of increasing importance in modern
      medicine. Regularly, antimicrobial therapy fails without removal of the implanted
      device. The most important factor in the pathogenesis of biomaterial-associated
      staphylococcal infections is the formation of adherent, multilayered bacterial
      biofilms. In this review, recent insights regarding factors functional in biofilm
      formation of S. epidermidis, their role in pathogenesis, and regulation of their
      expression are presented. Similarly, in S. aureus the biofilm mode of growth
      affects gene expression and the overall metabolic status. Experimental approaches
      for analysis of differential expression of genes involved in these adaptive
      responses and evolving patterns of gene expression are discussed.

PMID- 15493832
TI  - [Effects of puerarin on renal function, expressions of MMP-2 and TIMP-2 in
      diabetic rats].
AB  - AIM: To investigate the effect of puerarin on expressions of MMP-2 and TIMP-2 in
      the kidney of diabetic rats. METHODS: Uninephrectomized male Wistar rats were
      used to induce diabetes by intraperitoneal injection of streptozocin (65 mg x kg(
      1)). Puerarin was given daily by intraperitoneal injection from the third day of
      induction of diabetes for 16 weeks. Using in situ hybridization and
      immunohistochemistry to detect MMP-2, TIMP-2 mRNA expressions and MMP-2, TIMP-2,
      collagen IV and Laminin expressions in diabetic kidneys with image analysis
      system, Flow cytometry was used to detect the expressions of TGFbeta1, MMP-2 and
      TIMP-2. RESULTS: Compared with those in kidneys of control group, expressions of
      MMP-2 mRNA and proteins were lower, while the expressions of both TGFbeta1 and
      TIMP-2 were higher in the diabetic kidney (P < 0.05). The level of MMP-2
      expression was advanced, while expression of TIMP-2 was reduced by puerarin
      treatment (P < 0.05). CONCLUSION: Puerarin showed some renal protective effect on
      diabetic nephropathy, partly through inhibition of excessive deposition of
      glomeruli extracellular matrix by up-regulating MMP-2 and down-regulating TIMP-2
      expressions besides reducing the blood glucose.

PMID- 15493833
TI  - [Effect of inhaled cyclosporin A on antigen-induced airway inflammation in
      asthmatic rats].
AB  - AIM: To investigate the effect of inhalation of cyclosporin (CsA) on antigen
      induced airway inflammation in Sprague-Dawley rats. METHODS: Rats were sensitized
      with antigen (ovalbumin, OA). After two weeks, the sensitized rats were
      pretreated with aerosol CsA (5, 10, 20 g x L(-1)), once per day for 7 days. Then,
      the sensitized rats were challenged with OA (10 g x L(-1), once per day) for 2
      days at day 20 after sensitization. The number of eosinophils in bronchoalveolar
      lavage fluid (BALF) and peripheral blood, histological changes of lung tissue,
      and TNF-alpha content in BALF were investigated. RESULTS: Inhalation of CsA
      significantly reduced the number of eosinophils in BALF and peripheral blood,
      inflammatory infiltration and tissue edema of lung tissue, decreased the content
      of TNF-alpha in BALF. CONCLUSION: Inhalation of CsA inhibited airway inflammation
      in rats, and the mechanism is related to inhibition of TNF-alpha release.

PMID- 15493834
TI  - [Antitumor mechanism of 3-bromopropionylamino benzoylurea on leukemia and
      lymphoma].
AB  - AIM: To study the antitumor mechanism of 3-bromopropionylamino benzoylurea
      (JIMB01) on leukemia and lymphoma. METHODS: The antitumor effects of JIMB01 in
      cell culture was detected by MTT staining. JIMB01-induced apoptosis in leukemia
      and lymphoma cells was tested by Giemsa staining, fluorescent Hoechst33258
      staining, as well as DNA gel electrophoresis. Cell cycle was analyzed by flow
      cytometry. JIMB01-induced Bcl-2 phosphorylation in CEM cell lines was detected by
      Western blot methods. The activities of caspase-3 and caspase-8 were determined
      by colorimetric protease assay and that of caspase-9 was determined by
      fluorescent intensity. RESULTS: This compound showed antiproliferative activities
      in a panel of nine human leukemia and lymphoma cell lines with IC50 values in the
      range of 0.25 micromol x L(-10 to 0. 51 micromol x L(-1). Morphological
      observation and cell cycle analysis indicated that CEM cells were blocked at
      mitosis phase by JIMB01. The fluorescent Hoechst33258 staining showed apoptotic
      nuclear degradation dispersed in the cytoplasm of CEM cells exposed to JIMB01 at
      0. 80 micromol x L(-1) for 24 h. DNA degradation in the form of a multiple-unit
      DNA ladder was clearly demonstrated in CEM leukemia cells treated with JIMB01 at
      0.15 micromol x L(-1) or higher for 24 h using agarose gel electrophoresis. Bcl-2
      phosphorylation became visible, in Western blot, within 6 h in CEM cells treated
      with JIMB01 at 0.15 micromol x L(-1) or higher for 24 h. JIMB01 increased the
      activities of caspase-3, -8 and -9 in CEM cells; DEVD-fmk, a caspase-3 inhibitor,
      inhibited the cytotoxicity of JIMB01 in CEM leukemia cells. CONCLUSION: The
      antitumor mechanism of JIMB01 is that JIMB01 may induce tumor cell apoptosis
      through Bcl-2 phosphorylation and then caspase passway.

PMID- 15493835
TI  - [Salvianolic acid A inhibits nucleoside transport and potentiates the antitumor
      activity of chemotherapeutic drugs].
AB  - AIM: To investigate the inhibitory activity of salvianolic acid A (SAA) on
      nucleoside transport in cancer cells and its antitumor effect. METHODS: [3H]
      thymidine and [3H] uridine transport assays were used to determine the inhibitory
      activity on nucleoside transport in Ehrlich carcinoma cells. The cytotoxicity to
      cultured cancer cells was examined with clonogenic assay. The antitumor effect in
      vivo was evaluated with transplantable tumor model in mice. RESULTS: SAA was
      shown to inhibit thymidine and uridine transport in Ehrlich carcinoma cells with
      IC50 values of 18.1 and 17.1 micromol x L(-1), respectively. By clonogenic assay,
      the IC50 of SAA for KB cells was 44.7 micromol x L(-1). SAA markedly potentiated
      the cytotoxicity of 5-FU and mitomycin C in KB cells as well as the cytotoxicity
      of MTX in human hepatoma BEL-7402 cells. For in vivo experiment, sarcoma 180
      cells were transplanted sc in mice and tested drugs were administered ip. When
      administered separately, SAA at 200 mg x kg(-1) and 5-FU at 10 mg x kg(-1)
      inhibited tumor growth by 41% and 27%, respectively. Combination of the two drugs
      inhibited tumor growth by 63% (CDI = 0.86). CONCLUSION: SAA is active in blocking
      nucleoside transport in cancer cells and potentiates the cytotoxicity of
      chemotherapeutic drugs. As an agent showing moderate antitumor effect in vivo,
      SAA might be useful in combination cancer therapy.

PMID- 15493836
TI  - [Effects of cyclovirobuxine D on intracellular Ca2+ and L-type Ca2+ current in
      rat ventricular cardiomyocytes].
AB  - AIM: To determine the effects of cyclovirobuxine D (CD) on intracellular Ca2+
      mobilization and L-type Ca2+ current (I(Ca-L)) in isolated rat cardiomyocytes.
      METHODS: The effects of CD on the amplitude of I(Ca-L) and intracellular Ca2+
      mobilization induced by KCl and caffeine were studied with the method of patch
      clamp technique and laser scanning confocal microscopy in rat ventricular
      myocytes. RESULTS: CD decreased the amplitude of I(Ca-L) in a concentration
      dependent manner. At 10 mV, 1 and 10 micromol x L(-1) CD decreased I(Ca-L)
      density from (- 9.9 +/- 1.8) pA/pF to (-6.4 +/- 1.4) and (-4.2 +/- 0.6) pA/pF,
      respectively. Confocal experiments showed that intracellular fluorescent
      intensity (FI) value of [Ca2+] in control resting level was not changed by 1 and
      10 micromol x L(-1) CD. [Ca2+] increase in response to KCl could not be reduced
      by CD. The rise of [Ca2+]i in response to caffeine was further enhanced by
      pretreatment with CD. CONCLUSION: CD decreased I(Ca,L) in a concentration
      dependent manner and increased [Ca2+]i release induced by caffeine in rat
      ventricular cardiomyocytes.

PMID- 15493837
TI  - [Anti-arrhythmic effect of starfish sterol].
AB  - AIM: To study the effect of modified starfish sterol [C03, succinic acid (5
      epiandroene-17-one-3beta-ol) diester] on experimental arrhythmias. METHODS:
      Arrhythmias were induced by drugs (Aco, Oua, BaCl2 and adrenalin) i.v., ligating
      the left anterior descending coronary artery and electricity. RESULTS: C03 71.4
      mg x kg(-1) (ig) was shown to increase the dose of Oua inducing VP, VT, VF and CA
      in guinea pigs (P < 0.01); C03 (26.8, 80.4 mg x kg(-1)) was found to increase the
      dose of Aco inducing VF and CA in rats (P < 0.01); C03 (8.9, 26.8, 80.4 mg x kg(
      1)) increase the dose of barium chloride and delay the onset time of ventricular
      arrhythmias (P < 0.01); C03 (14.1, 42.3 mg x kg(-10) shorten time of recovering
      induced by adrenalin in rabbits (P < 0.01); C03 (80.4 mg x kg(-1)) was shown to
      reduce the number of ventricular arrhythmias induced by coronary artery ligation
      in rats (P < 0.05), C03 increase VFT induced by electricity in rabbits, VFT of
      C03 14.1 mg x kg(-1) increased from (5.1 +/- 2.5) V to (11.0 +/- 2.7) V (P <
      0.01), 42.3 mg x kg(-1) increased from (6.1 +/- 1.7) V to (15 +/- 5) V (P <
      0.01). CONCLUSION: Starfish sterol has anti-arrhythmic effect.

PMID- 15493838
TI  - Effects of amiloride on potassium and calcium currents in guinea pig ventricular
      myocytes.
AB  - AIM: To elucidate the possible mechanisms underlying antiarrhythmia of the non
      selective Na+/H+ exchanger inhibitor--amiloride. METHODS: Single ventricular
      cells were isolated using a double-enzyme method. Effects of amiloride on voltage
      dependent potassium and calcium currents in isolated guinea pig ventricular
      myocyte were recorded by using whole-cell patch clamp techniques. RESULTS:
      Exposure to amiloride (10 -100 micromol x L(-1)), the L-type and T-type calcium
      currents were depressed. Amiloride resulted in a concentration-dependent
      inhibition of peak (Ca,L), But amiloride did not change the shape of their I - V
      curves. It only decreased the amplitudes of the currents of the two types. When
      myocytes were incubated with 100 micromol x L(-1) amiloride, I(Kr) was slightly
      depressed and I(Ks) did not change. Amiloride (1 - 100 micromol x L(-10)
      depressed I(K1) in a concentration-dependent manner. CONCLUSION: Amiloride
      depressed potassium and calcium currents, which may give support to its uses in
      some diseases of the cardiovascular system.

PMID- 15493840
TI  - [Synthesis and anti-inflammatory activity of N-(4-arylamidophenyl)
      methanesulfonamide derivatives].
AB  - AIM: To study the anti-inflammatory activity of N-(4-arylamidophenyl)
      methanesulfonamide derivatives. METHODS: The target compounds were synthesized
      from p-nitroaniline via three steps and were evaluated for anti-inflammatory
      activity with the model of xylene-induced ear edema in mice. RESULTS: Eleven
      compounds were obtained and confirmed by IR, 1HNMR and MS. Some compounds were
      shown to have significant anti-inflammatory activity. CONCLUSION: N-(4
      arylamidophenyl) methanesulfonamide showed appreciable anti-inflammatory
      activity.

PMID- 15493839
TI  - [Ameliorations of pioglitazone on insulin resistance in spontaneous IGT-OLETF
      rats].
AB  - AIM: To investigate the ameliorations of pioglitazone, a member of the
      thiazolidinedione group of antidiabetic agents, on insulin resistance in
      spontaneous OLETF rats with impaired glucose tolerance (IGT-OLETF). METHODS: One
      group of IGT-OLETF rats was orally administered pioglitazone at the dose of 20 mg
      x kg(-1) (qd) for 2 weeks. Another group was given the same volume of solvent as
      control. Glucose tolerance and insulin tolerance were tested, and blood glucose
      concentrations, insulin levels and lipids in serum, liver and muscle were
      determined. Insulin sensitive index (ISI) was calculated by the reciprocal of
      fasting blood glucose times fasting insulin. RESULTS: Pioglitazone was shown to
      markedly enhance the glycemic response to exogenous insulin (0. 4 x kg(-1), sc)
      in the model. The falls of blood glucose at 40 and 90 min in the insulin
      tolerance test were augmented by 70% and 158% in the treated group than the
      control. The serum insulin levels were significantly decreased and the ISI nearly
      normalized after treatment. Pioglitazone also lowered the serum TG and FFA levels
      and the lipids in liver and muscle. No effect was found on the expression of
      leptin in epididymal adipose tissues and on the activity of GFAT, a key enzyme in
      hexosamine biosynthesis pathway (data were not shown). CONCLUSION: Pioglitazone
      can improve the insulin resistance state in IGT-OLETF rats. Correction of lipid
      disorder may be associated with it.

PMID- 15493841
TI  - [Synthesis and antitumor activities of 10-hydroxy camptothecin derivatives].
AB  - AIM: To find new anticancer drug based on the structure of 10-hydroxy
      camptothecin. METHODS: Seven camptothecin derivatives (3 -9) were synthesized and
      the antitumor activities of these derivatives were evaluated. RESULTS: Structures
      of seven new compounds were determined by 1HNMR, IR, MS. Seven compounds showed
      inhibitory effects on Hela, BEL-7402, 7901 cell lines in vitro. Especially,
      compound 4 showed high bioactivities to all of the tumor cells in vitro, its
      anticancer activity against human cervical carcinoma Hela was much higher than
      that of 10-hydroxy camptothecin. CONCLUSION: Some compounds are worth further
      studying.

PMID- 15493842
TI  - [Structure identification of two new cerebrosides from Helicia nilagirica Beed].
AB  - AIM: To study the bioactive components from Helicia nilagirica. METHODS:
      Compounds were separated with a combination of multi-chromatography. Their
      chemical structures were determined on the basis of spectral analysis and
      chemical evidence. RESULTS: Two compounds were isolated from the leaves of
      Helicia nilagirica. Compound 1 was elucidated as 1-O-3-D-glucopyranosyl
      (2S,3S,4R,8Z)-2-[(2'R)-2'-hyd roxylignocenoyl-amino]-8-octadecene-1, 3, 4-triol.
      Compound 2 was an analogue of 1. CONCLUSION: The two compounds are new
      cerebrosides.

PMID- 15493843
TI  - [The isolation and identification of two new epimer from the mother liquid of
      testosterone].
AB  - AIM: To study the impurity of the drug testosterone. METHODS: Chromatography
      methods were used to separate the chemical constituents. Their structures were
      determined by NMR and MS spectral analysis. RESULTS: Two new epimers were
      isolated from the mother liquid of the drug. CONCLUSION: These new epimers were
      identified as 3alpha-ethoxyandrost-4-en-17beta-ol, 3beta-ethoxyandrost-4-en
      17beta-ol.

PMID- 15493844
TI  - [A new lignan glycoside from the flower of Castanea mollissima Blume].
AB  - AIM: To study the bioactive constituents of the flower of Castanea mollissima
      Blume. METHODS: Compounds were isolated and purified by column chromatography of
      silica gel and TLC. Structures were determined by various spectroscopic data,
      including IR, 1HNMR and 13CNMR, EIMS, FABMS and HMBC as well as comparison of the
      data with those reported in literatures. RESULTS: Five compounds were isolated
      and elucidated as myricetin (I), quercetin (II), gallic acid (III), 4-quinolinone
      2-caboxylic acid (IV), (+) -isolariciresinol-9'-O-alpha-L-rhamnoside (V).
      CONCLUSION: These compounds were separated from the flower for the first time and
      compound V is a new compounds, named chestnutlignansoide.

PMID- 15493845
TI  - [Identification of the structure of two new nitro group phenolic glycosides from
      Schisandra propinqua (Wall. ) Baill var. intermidia A. C. Smith].
AB  - AIM: To study the bioactive components from Schisandra propinqua (Wall.) Baill
      var. intermidia A. C. Smith. METHODS: Compounds were separated with a combination
      of multichromatography. Their chemical structures were determined on the basis of
      spectral analysis and chemical evidence. RESULTS: Seven compounds were isolated
      from the leaves of Helicia nilagirica. The structures were elucidated as 6'-O
      alpha-L-arabinofuranosylthalictoside (1), 6'-O-beta-D-apiofuranosylthalictoside
      (2), thalictoside (3), icariside D2 (4), prinsepiol (5), (+)-1-hydroxypinoresinol
      (6) and (+)-medioresinol (7). CONCLUSION: Two compounds are new nitro phenolic
      glycosides.

PMID- 15493846
TI  - [Polarograhic adsorptive wave of protein hydrolysate in Pb2+ and sodium hydroxide
      solution and its application].
AB  - AIM: To propose a new simple and sensitive voltammetric method for determination
      of proteins. METHODS: Protein with sulfhydryl or disulfide bond in 0.5 mol x L(
      1) NaOH, 1.5 x 10(-4) mol x L(-1) Pb2+ and 0.02% tetrabutylammonium iodide was
      heated in boiling water for 5 minutes. The reactive product gave a well defined
      reductive adsorption wave at -0.66 V (vs SCE) by means of single sweep
      polarography, and the height of derivative wave was proportional to the
      concentration of proteins. RESULTS: The peak height was linearly proportional to
      bovine serum albumin (BSA) or human serum albumin (HSA) concentration in range of
      7.5 x 10(-10) -3.0 x 10(-7) mol x L(-1) (r(BSA) = 0.9995, and r(HSA) = 0.9990).
      The detection limit of BSA or HSA was 3.0 x 10(-10) mol x L(-1). For lysozyme
      (Lyso), the concentration range was from 1.4 x 10(-8) to 1.3 x 10(-6) mol x L(-10
      (r(Lyso) = 0.9997) and the detection limit was 7.0 x 10(-9) mol x L(-1).
      CONCLUSION: The method is simple, rapid, sensitive and applicable to the assay of
      diluted human serum albumin samples.

PMID- 15493847
TI  - [Determination of octreotide in human plasma by HPLC-MS with solid-phase
      extraction and study on the relative bioavailability of domestic and imported
      octreotide injections].
AB  - AIM: To establish an HPLC-MS method for determination of octreotide in plasma and
      study the relative bioavailability of domestic and imported octreotide
      injections. METHODS: Octreotide in plasma samples were extracted with a Waters
      solid-phase extraction mini column. HPLC-MS was carried out using a Waters Xetrra
      C18 column and a mobile phase consisting of CH3 OH-1% HAc (80 : 20), the flow
      rate was 0.2 mL x min(-1), and the internal standard was 6, 7, 4'-OH-isoflavone,
      the SIR ions for quantification were m/z 1 014.4 for octreotide and m/z 317.6 for
      internal standard. A single dose of 200 microg of domestic or imported
      preparations was intramuscularly given to 18 healthy volunteers in a randomized
      crossover study. Octreotide concentration in plasma was determined by LC-MS
      method. The pharmacokinetics and bioavailability were studied. RESULTS: The
      regressive curve was linear (r = 0.9997) within the range of 0.5 - 40 microg x L(
      1) for octreotide. The pharmacokinetics parameters of domestic and imported
      injection were reply to one compartment model. The mean C(max) were (19 +/- 10)
      microg x L(-1) and (19 +/- 11) microg x L(-1), T(max) were (0.50 +/- 0.15) h and
      (0.52 +/- 0.20) h, T1/2 were (1.5 +/- 0.8) h and (1.5 +/- 0.8) h, AUC(0-7 h) were
      (50 +/- 25) h x microg x L(-1) and (50 +/- 25) h x microg x L(-1), respectively.
      The relative bioavailability of domestic to imported injection was 101% +/- 10%.
      CONCLUSION: The method is accurat and sensible for assay of plasma octreotide
      concentration. The results of statistics showed the two preparations were
      bioequivalent.

PMID- 15493848
TI  - Structural characterization of chlorobenzylidine.
AB  - AIM: To study the structure and crystal forms of chlorobenzylidine. METHODS: Karl
      Fischer titrimetry, FTIR, thermal analysis, single and powder X-ray diffraction
      were used for the studies of the structure of chlorobenzylidine and for the
      identification of two forms of chlorobenzylidine. RESULTS: Chlorobenzylidine and
      its diastereoisomer have been studied in this article. They can be distinguished
      by their different melting points. Two crystal forms of chlorobenzylidine (form A
      and form B) have also been detected and studied. Form A was studied by single
      crystal X-ray diffraction, it crystallized in the triclinic system, space group
      P1(-), with two formula units per cell, is monohydrate. Karl Fischer titrimetry,
      FTIR, thermal analysis and powder X-ray diffraction were used for identification
      of the two forms. CONCLUSION: The studies of structure and crystal forms of
      chlorobenzylidine are very useful for the clinical research and the selection of
      recrystallization process.

PMID- 15493849
TI  - [Biodistribution and hepatocytes targeting of cationic liposomes surface-modified
      with sterylglucoside and golyethylene glycol].
AB  - AIM: To investigate the biodistribution and the hepatocytes targeting of cationic
      liposome containing 3beta[N-( N',N'-dimethylaminoethane) carbamoyl] cholesterol
      (DC-Chol) and surface-modified liposomes with sterylglucoside (SG) and
      polyethylene glycol-distearoylphosphatidylethanolamine (PEG-DSPE). METHODS:
      Cationic liposomes (CL) composed of DC-Chol and dipalmitoylphosphatidylcholine
      (DPPC), SG/PEG modified cationic liposome (SG/PEG-CL), both contained trace 3H
      cholesterol (3H-Chol) as radiolabel, were prepared. The liposomes encapsulating
      125I-labled antisense oligodeoxynucleotide (125I-asODN) (SG/PEG-CL-asODN) were
      also prepared. The biodistribution of CL, SG/PEG-CL, SG/PEG-C2-asODN as well as
      125I-asODN solution, were studied. The radioactivities in hepatocytes and non
      hepatocytes after administration of CL and SG/PEG-CL were determined by infuseing
      method. RESULTS: CL and SG/PEG CL significantly aggregated in liver. The
      distribution of SG/PEG CL was significantly higher in hepatocytes (P < 0.01) and
      lower in non-hepatocytes (P < 0.01) than that of CL. The concentrations of SG/PEG
      CL-asODN in liver and spleen were significantly higher than that of asODN
      solution (P < 0.01). CONCLUSION: Cationic liposome modified with SG/PEG changed
      the distribution of asODN. Cationic liposome can target hepatocytes more
      effective after being modified with SG.

PMID- 15493850
TI  - [Preparation and toxicity of triptolide-loaded poly (D,L-lactic acid)
      nanoparticles].
AB  - AIM: Investigations on reducing the toxicity of triptolide through poly(D, L
      lactic acid) nanoparticles as a drug carrier by oral administration to Wistar
      rats. METHODS: Triptolide-loaded poly (D, L-lactic acid) nanoparticles (TP-PLA
      NPs) were prepared by modified spontaneous emulsification solvent diffusion
      (modified-SESD). The shape of nanoparticles was observed by transmission electron
      microscope (TEM). The size distribution and mean diameter were measured by laser
      light scattering technique. The entrapment efficiency and contents of drug
      loading were determined by RP-HPLC. The physical state of drug loaded in
      nanopartiles were primarily investigated by X-ray powder diffractometry. TP-PLA
      NPs release behavior in vitro was carried out. After oral administration of the
      nanoparticles to Wistar rats in 15d, the toxicity for liver and kidney were
      studied by determining aspartate transaminase (AST), alanine transaminase (ALT)
      and blood urea nitrogen in serum and concentration of protein in urine. RESULTS:
      The preparation process adapted to the formulation was as follows: the volume
      ratio of the aqueous and organic phases was 40/15; the surfactant concentration
      was 1%; the drug concentration was 0.3%; triptolide-PLA was 1:15 (w/w). The mean
      diameter was 149.7 nm and the polydispersity index was 0. 088 for the
      nanoparticles prepared by above conditions. The entrapment efficiency and content
      of drug loading were 74.27% and 1.36%, respectively. The release behavior of drug
      in vitro showed an initial burst effect, subsequently a slower rate stage. The
      results indicated that the liver toxicity (P < 0.01) and kidney toxicity (P <
      0.05) caused by triptolide could be decreased significantly by nanoparticles
      carrier. CONCLUSION: PLA-NPs might be used as a new oral carrier for triptolide.

PMID- 15493851
TI  - [Studies on the influencing factors on the drug release from sodium alginate
      matrices].
AB  - AIM: To investigate the in vitro influencing factors on drug release from
      matrices with sodium alginate as the hydrophilic polymer. METHODS: Sodium
      alginate hydrophilic matrix tablets were prepared by direct compression method
      with theopylline as a model drug. The in vitro influencing factors on drug
      release behavior from matrices were studied by investigating the swelling, water
      uptake and erosion characteristics of pure sodium alginate matrices. RESULTS: The
      results showed that drug release rate and drug release mechanism were both
      related to the viscosity of sodium alginate used in matrices, pH values and ionic
      strength of dissolution media and rotation speeds. CONCLUSION: Sodium alginate
      can be tailor-made to suit the demands of applicants in sustained delivery
      systems as a good candidate of hydrophilic polymer.

PMID- 15493852
TI  - [Application of capillary electrophoresis in analysis of cell and its
      components].

PMID- 15493853
TI  - [Application of mass spectrometry to combinatorial chemistry].

PMID- 15493854
TI  - Brave new world inches closer.

PMID- 15493855
TI  - Beyond Nightingale: the science of contemporary nursing.

PMID- 15493856
TI  - Gastric residual volumes in critically ill paediatric patients: a comparison of
      feeding regimens.
AB  - This study examined the effect of gastric feeding regimens, either continuous or
      intermittent, on fourth hourly gastric residual volumes (GRV) in a group of
      critically ill paediatric patients where delayed gastric emptying is defined as a
      GRV greater than 5ml/kg. A randomised controlled trial was conducted in a
      tertiary paediatric intensive care unit (PICU), with 45 participants being
      randomly assigned to either the continuous (n=22) or intermittent (n=23) gastric
      feeding groups. Participants remained in the assigned group for the duration of
      the study and, fourth hourly, GRV were assessed to monitor the incidence of
      delayed gastric emptying. Both groups were similar in age, weight, gender,
      diagnosis, paediatric index mortality (PIM) score, and usage of pharmacological
      agents known to affect the gastrointestinal tract. No differences emerged in
      study duration or the volume of administered enteral formula (ml/kg/day). The
      intermittent feeding group commenced enteral feeding earlier in the PICU
      admission (13.0 hours versus 18.5 hrs, p=0.05). Repeated measures analysis
      revealed no overall difference in median GRV/kg values between treatment groups
      over the 72 hour study period. Additionally, the incidence of fourth hourly GRV,
      greater than 5ml/kg, was not different between the continuous and intermittent
      feeding groups. The provision of enteral nutrition via the gastric route is a
      common treatment in the PICU, and GRV are frequently used as a measure of gastric
      tolerance. The result of this analysis provides some support for the theoretical
      definition of delayed gastric emptying being >5ml/kg. However, further work is
      required to confirm this finding and to determine its relevance when providing
      enteral nutrition to the critically ill paediatric patient.

PMID- 15493857
TI  - Chest x-ray quiz. Multiple right side rib fractures and surgical emphysema, lung
      contusion, pneumothorax with chest drain and deep sulcus sign.

PMID- 15493858
TI  - The effect of chronic pain on health related quality of life amongst intensive
      care survivors.
AB  - Intensive care unit (ICU) survivors report reductions in health-related quality
      of life (HR-QOL), whilst chronic pain is common in the general population.
      However, it is unknown whether there are associations between the experience of
      ICU and the incidence of chronic pain. A questionnaire--Pain Scale, Pain Self
      Efficacy Questionnaire (PSEQ), Centre of Epidemiology Study Depression Scale (CES
      D Scale) and the Short Form Health Survey (SF-36)--was sent to 99 consenting
      patients who had been in the ICU for >48 hours. Sixty-six and 52 questionnaires
      were returned at 1 and 6 months respectively. There was a general limitation in
      activities of daily living; younger ages (36-65 years) experienced a decease in
      work performance and other physical activities. Bodily pain increased, general
      health diminished, and engagements in social activities were severely affected.
      There was a decline in mental health for those 36-65 years of age. HR-QOL
      improved over time; 28% experienced chronic pain and had longer hospital length
      of stay (LOS), tended to have longer ICU LOS and were ventilated for longer.
      Those with chronic pain had significant reductions in physical function, bodily
      pain, general health and vitality. Ventilator hours and hospital LOS were
      associated with risk of chronic pain (OR 1.09, p=0.033 and OR 1.27, p=0.046). HR
      QOL in ICU survivors declined, although there was a general improvement from 1-6
      months. This decline in HR-QOL affected younger people (less than 65 years) more
      than older people. Chronic pain is a significant issue post ICU and is associated
      with poorer HR-QOL.

PMID- 15493859
TI  - The meaning of effective education for critical care nursing practice: a thematic
      analysis.
AB  - Continuing education and practice development are integral components of
      specialist nursing practice in environments such as intensive and critical care.
      Previous studies have examined the 'effectiveness' of various approaches to
      teaching and learning in critical care, yet few have considered how effective
      education affects the relationship between education and practice development.
      Using thematic analysis, this study explored the phenomenon of effective
      education (for critical care nursing practice) by asking: What does effective
      education for critical care nursing practice mean to nurses currently practising
      in the specialty? Eighty eight critical care nurses from the South Island of New
      Zealand provided written descriptions of what effective education for critical
      care nursing practice meant to them. Descriptive statements were analysed to
      reveal constituents, themes and essences of meaning. Four core themes of personal
      quality, practice quality, the learning process and learning needs emerged.
      Appropriateness or relevance for individual learning needs is further identified
      as an essential theme within the meaning of effective education for critical care
      nursing practice. Shared experiences of the phenomenon are made explicit and
      discussed with reference to education and practice development in the specialty.
      The study results lend support to education that focuses on individual learning
      needs, and identifies work based learning as a potential strategy for learning
      and practice development in critical care nursing.

PMID- 15493860
TI  - Critical care nurses' perceptions about their involvement in significant
      decisions regarding patient care.
AB  - The purpose of the study was to explore and describe the perceptions of critical
      care nurses' (CCNs) actual and preferred levels of involvement in significant
      decisions regarding patient care in critical care areas. A convenience sample of
      CCNs was recruited from two centres (one public and one private) and a researcher
      generated survey distributed to participants. Of the 131 questionnaires
      distributed, 90 were completed, giving a response rate of 68.7%. Results showed
      that, although most CCNs believed that they had important information to
      contribute to decisions relating to patient care, less than half felt that they
      were actively involved in such decisions. They were aware of the legal limits to
      their scope of practice but, despite this, most admitted that they made decisions
      beyond these limits. Approximately three quarters of the respondents thought CCNs
      should not be making decisions beyond legal boundaries. On the whole, CCNs wanted
      to be more involved formally and to have more power in decisions regarding
      patient care. One way forward is for the CCNs to have an advanced practice role.

PMID- 15493861
TI  - [Andras Peto conductive promotion].

PMID- 15493862
TI  - [100 years Red Cross nurses in Krefeld].

PMID- 15493863
TI  - [What is the role of large muscle performance in children with severe specific
      language development disorder?].

PMID- 15493864
TI  - [Pain, it's therapy and modification of early childhood development in premature
      infants].

PMID- 15493865
TI  - [5 years educational focus on promotion of gifted children in health specialty
      careers--a success story].

PMID- 15493866
TI  - [Value of kangaroo care, basal stimulation, kinesthesis awareness and baby
      massage in development promoting nursing of premature infants].

PMID- 15493867
TI  - [Do experiences in childhood contribute to selection of pediatric nursing as a
      career? A study using a questionnaire].

PMID- 15493868
TI  - [Duchenne muscular dystrophy. Current brief description].

PMID- 15493869
TI  - [Poisonous monitor. The toxic chemical phenol].

PMID- 15493870
TI  - Tapasin and other chaperones: models of the MHC class I loading complex.
AB  - MHC (major histocompatibility complex) class I molecules bind intracellular virus
      derived peptides in the endoplasmic reticulum (ER) and present them at the cell
      surface to cytotoxic T lymphocytes. Peptide-free class I molecules at the cell
      surface, however, could lead to aberrant T cell killing. Therefore, cells ensure
      that class I molecules bind high-affinity ligand peptides in the ER, and restrict
      the export of empty class I molecules to the Golgi apparatus. For both of these
      safeguard mechanisms, the MHC class I loading complex (which consists of the
      peptide transporter TAP, the chaperones tapasin and calreticulin, and the protein
      disulfide isomerase ERp57) plays a central role. This article reviews the actions
      of accessory proteins in the biogenesis of class I molecules, specifically the
      functions of the loading complex in high-affinity peptide binding and
      localization of class I molecules, and the known connections between these two
      regulatory mechanisms. It introduces new models for the mode of action of
      tapasin, the role of the class I loading complex in peptide editing, and the
      intracellular localization of class I molecules.

PMID- 15493871
TI  - Expression analysis of BCL2L12, a new member of apoptosis-related genes, in colon
      cancer.
AB  - Apoptosis is an active process regulated by a variety of genes. Recently, the
      molecular cloning, physical mapping and expression analysis of a novel gene of
      the Bcl-2 family, BCL2L12, was reported. Expression analysis of the BCL2L12 gene
      in breast cancer confirmed an association of BCL2L12 with favorable prognosis of
      patients. In the present study, the expression of the BCL2L12 gene was analyzed
      in colon cancer by RT-PCR. Two transcripts, BCL2L12 and BCL2L12-A, were
      overexpressed in the cancer tissues as compared to their paired normal mucosa. An
      association was found between BCL2L12-A transcript expression and nodal status,
      as well as Dukes' stage. The BCL2L12-A transcript appears to be of importance for
      colon cancer since its expression is associated with disease progression.

PMID- 15493872
TI  - SR-A1, a member of the human pre-mRNA splicing factor family, and its expression
      in colon cancer progression.
AB  - SR (serine-arginine) proteins are essential pre-mRNA splicing factors. Several SR
      proteins have been characterized in humans, among them SR-A1. It has been
      demonstrated by members of our group that the SR-A1 gene is constitutively
      expressed in most of the human tissues, while its transcription is increased in
      breast carcinoma cell lines. Moreover, the SR-A1 gene is overexpressed in a set
      of ovarian tumors, suggesting that it may be involved in the pathogenesis and/or
      progression of ovarian cancer. Therefore, in the present study we examined the
      expression of the SR-A1 gene in colon cancer tissues by RT-PCR and found that it
      is overexpressed as compared to normal mucosa (p=0.01). The SR-A1 gene was
      expressed more frequently in well-differentiated tumors than those with poor
      differentiation. Survival curves determined by the Kaplan-Meier method and
      univariate analysis demonstrated that SR-A1-positivity is associated with a long
      survival (p=0.044). However, when entered into a Cox multivariate model adjusted
      for other clinicopathological features studied, SR-A1 expression status was not
      found to be of independent prognostic significance. To the best of our knowledge,
      this is the first study examining the expression of the novel gene SR-A1 in colon
      cancer progression.

PMID- 15493873
TI  - RNA interference by small hairpin RNAs synthesised under control of the human 7S
      K RNA promoter.
AB  - Small interfering RNAs (siRNAs) represent RNA duplexes of 21 nucleotides in
      length that inhibit gene expression. We have used the human gene-external 7S K
      RNA promoter for synthesis of short hairpin RNAs (shRNAs) which efficiently
      target human lamin mRNA via RNA interference (RNAi). Here we demonstrate that
      orientation of the target sequence within the shRNA construct is important for
      interference. Furthermore, effective interference also depends on the length
      and/or structure of the shRNA. Evidence is presented that the human 7S K promoter
      is more active in vivo than other gene-external promoters, such as the human U6
      small nuclear RNA (snRNA) gene promoter.

PMID- 15493874
TI  - Kinetic characterization of phenol and aniline derivates as substrates of
      peroxidase.
AB  - The kinetic characterization of horseradish peroxidase (HRPC) substrates is
      difficult because the reaction products are free radicals. The application of a
      spectrophotometrical method, which is based on determining the time necessary for
      a given quantity of L-ascorbic acid to be consumed (lag period) during its
      reaction with the free radicals generated by the enzyme acting on the reducing
      substrate, makes it possible to obtain the initial steady-state rates (v0). From
      the kinetic study of a series of derivates of phenol and aniline, the following
      parameters were determined for the first time: the global catalytic constant
      (kcat), the Michaelis constant of HRPC for H2O2 in the presence of each reducing
      substrate (K(M)H2O2), the Michaelis constant of HRPC for the reducing substrate
      (KMS), the binding constant of the reducing substrate with HRPC compound II (k5)
      and the rate constant of substrate oxidation by HRPC compound II (k6). The values
      obtained are disccussed.

PMID- 15493875
TI  - Non-muscle alpha-actinin-4 interacts with plasminogen activator inhibitor type-1
      (PAI-1).
AB  - PAI-1 modulates many biological processes involving fibrinolysis, cell migration
      or tissue remodelling. In addition to inhibiting serine proteases (mainly tPA and
      uPA), PAI-1 interacts with vitronectin (Vn), fibrin or alpha(1)-acid
      glycoprotein, interactions which are important for PAI-1-mediated effects in
      inflammation, tumor invasion and metastasis. To further identify proteins
      interacting with PAI-1, the yeast two-hybrid strategy was employed. Screening of
      a human placenta cDNA library identified--in addition to the C-terminal region of
      cytokeratin 18 (CK18(182-430))--a large C-terminal fragment of alpha-actinin-4
      (Act-4) as a binding partner for PAI-1. Two different cDNA clones encoding Act
      4(287-911) and Act-4(330-911) respectively, were isolated. An Act-4(330-911)/GST
      fusion protein, but not GST alone, was immunoprecipitated together with active
      PAI-1. In solid phase binding assays, active wild-type PAI-1 as well as the PAI-1
      variant Q123K (which does not interact with multimeric Vn) was found to bind to
      Act-4(330-911)/GST. Latent PAI-1, latent Q123K, and the inactive PAI-1 variant
      Q55P did not display any binding activity. Act-4 is mainly present
      intracellularly and is involved in cellular motility via interaction with the
      actin cytoskeleton, thus probably affecting the metastatic potential of tumor
      cells. However, an extracellular Act-4-derived fragment (mactinin) has previously
      been identified, which (i) is generated by proteolytic action of uPA, (ii)
      displays significant chemotactic activity for monocytes, and (iii) promotes
      monocyte/macrophage maturation. We suggest that PAI-1, via interaction with both
      Act-4 and uPA, may function as a modulator of this mononuclear phagocyte
      response, not only in inflammation but also in tumor invasion and metastasis.

PMID- 15493876
TI  - Oxidative modification of low-density lipoprotein: lipid peroxidation by
      myeloperoxidase in the presence of nitrite.
AB  - Oxidative modification of low-density lipoprotein (LDL) is a pivotal process in
      early atherogenesis and can be brought about by myeloperoxidase (MPO), which is
      capable of reacting with nitrite, a NO metabolite. We studied MPO-mediated
      formation of conjugated dienes in isolated human LDL in dependence on the
      concentrations of nitrite and chloride. This reaction was strongly stimulated by
      low concentrations (5-50 microM) of nitrite which corresponds to the reported
      concentration in the arterial vessel wall. Under these conditions no protein
      tyrosine nitration occurred; this reaction required much higher nitrite
      concentrations (100 microM-1 mM). Chloride neither supported lipid peroxidation
      alone nor was its presence mandatory for the effect of nitrite. We propose a
      prominent role of lipid peroxidation for the proatherogenic action of the
      MPO/nitrite system, whereas peroxynitrite may be competent for protein tyrosine
      nitration of LDL. Monomeric and oligomeric flavan-3-ols present in cocoa products
      effectively counteracted, at micromolar concentrations, the MPO/nitrite-mediated
      lipid peroxidation of LDL. Flavan-3-ols also suppressed protein tyrosine
      nitration induced by MPO/nitrite or peroxynitrite as well as Cu2+-mediated lipid
      peroxidation of LDL. This multi-site protection by (-)-epicatechin or other
      flavan-3-ols against proatherogenic modification of LDL may contribute to the
      purported beneficial effects of dietary flavan-3-ols for the cardiovascular
      system.

PMID- 15493878
TI  - Inhibition of inducible TNF-alpha expression by oxaspirodion, a novel spiro
      compound from the ascomycete Chaetomium subspirale.
AB  - In a search for compounds inhibiting the inducible TNF-alpha promoter activity in
      T cells, a new spiro-compound, designated oxaspirodion, was isolated from
      fermentations of the ascomycete Chaetomium subspirale. Oxaspirodion inhibited TNF
      alpha promoter-driven luciferase reporter gene expression with an IC50 value of
      2.5 microg/ml (10 microM) in TPA/ionomycin-stimulated Jurkat T cells. Studies on
      the mode of action of the compound revealed that the inhibition of the TNF-alpha
      promoter activity is caused by an inhibition of the phosphorylation of the ERK1/2
      kinases. In addition, oxaspirodion inhibited the activation of the transcription
      factor NF-kappaB, which is involved in the inducible expression of many
      proinflammatory genes.

PMID- 15493877
TI  - An apoptotic inducer, aralin, is a novel type II ribosome-inactivating protein
      from Aralia elata.
AB  - We recently found that aralin, a novel cytotoxic protein consisting of two
      subunits, from Aralia elata selectively induces apoptosis in transformed cells as
      compared to normal cells. Here we report that aralin is a lectin specific for
      galactose (Gal) and its derivatives, and possesses RNA N-glycosidase activity as
      a new type II ribosome-inactivating protein (RIP). The RNA N-glycosidase activity
      of aralin was detected in cell-free and whole cell systems by the generation of
      an R-fragment from 28S rRNA. Coinciding with appearance of the R-fragment in
      aralin-treated cells, significant inhibition of protein synthesis was observed
      prior to the onset of apoptosis. Aralin-evoked cell death was efficiently
      repressed by the addition of Gal and its derivatives. Interestingly, melibiose
      preferentially protected normal cells from apoptosis as compared with transformed
      cells. Using rhodamine-coupled aralin, the aralin receptor could be clearly
      detected around the cell surface of transformed cells, but to a lesser extent on
      normal cells. Receptor binding was suppressed by Gal. These results indicate that
      aralin is incorporated into cells via its Gal-containing cell surface receptor
      and induces apoptosis through its RIP activity. Moreover, the expression level
      and/or structural changes of the aralin receptor may affect the sensitivity
      toward aralin.

PMID- 15493879
TI  - Inhibition of sequestration of human B2 bradykinin receptor by phenylarsine oxide
      or sucrose allows determination of a receptor affinity shift and ligand
      dissociation in intact cells.
AB  - Depending on their interaction with intracellular proteins, G protein-coupled
      receptors (GPCR) often display different affinities for agonists at 37 degrees C.
      Determining the affinity at that temperature is often difficult in intact cells
      as most GPCRs are internalized after activation. When sequestration of the B2
      bradykinin receptor (B2R) was inhibited by either 0.5 M sucrose or phenylarsine
      oxide (PAO), a shift in the affinity was detected when the incubation temperature
      was raised from 4 degrees C to 37 degrees C or lowered from 37 degrees C to 4
      degrees C. In contrast, binding of the antagonist [3H]NPC 17731 was temperature
      independent. B2R mutants displayed different affinity shifts allowing conclusions
      on the role of the involved amino acids. By inhibiting receptor sequestration it
      was possible to determine also dissociation of [3H]BK and of [3H]NPC 17731 from
      intact cells at 37 degrees C. Surprisingly, both dissociation rates were markedly
      enhanced by the addition of unlabeled ligand, most likely via prevention of
      reassociation of dissociated [3H]ligand. This suggests that dissociated
      [3H]ligand cannot move freely away from the receptor. In summary, our data
      demonstrate that inhibition of receptor internalization either by PAO or sucrose
      provides an excellent method to study receptor function and the effects of
      mutations in intact cells.

PMID- 15493880
TI  - Effects of short-term chemical ablation of the GIP receptor on insulin secretion,
      islet morphology and glucose homeostasis in mice.
AB  - Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone
      secreted by endocrine K-cells in response to nutrient absorption. In this study
      we have utilized a specific and enzymatically stable GIP receptor antagonist,
      (Pro3)GIP, to evaluate the contribution of endogenous GIP to insulin secretion
      and glucose homeostasis in mice. Daily injection of (Pro3)GIP (25 nmol/kg body
      weight) for 11 days had no effect on food intake or body weight. Non-fasting
      plasma glucose concentrations were significantly raised (p<0.05) by day 11, while
      plasma insulin concentrations were not significantly different from saline
      treated controls. After 11 days, intraperitoneal glucose tolerance was
      significantly impaired in the (Pro3)GIP treated mice compared to control
      (p<0.01). Glucose-mediated insulin secretion was not significantly different
      between the two groups. Insulin sensitivity of 11-day (Pro3)GIP treated mice was
      slightly impaired 60 min post injection compared with controls. Following a 15
      min refeeding period in 18 h fasted mice, food intake was not significantly
      different in (Pro3)GIP treated mice and controls. However, (Pro3)GIP treated mice
      displayed significantly elevated plasma glucose levels 30 and 60 min post feeding
      (p<0.05, in both cases). Postprandial insulin secretion was not significantly
      different and no changes in pancreatic insulin content or islet morphology were
      observed in (Pro3)GIP treated mice. The observed biological effects of (Pro3)GIP
      were reversed following cessation of treatment for 9 days. These data indicate
      that ablation of GIP signaling causes a readily reversible glucose intolerance
      without appreciable change of insulin secretion.

PMID- 15493881
TI  - Comprehensive analysis of metabolites in Corynebacterium glutamicum by gas
      chromatography/mass spectrometry.
AB  - An analytical method based on gas chromatography/mass spectrometry was developed
      for metabolome investigation of Corynebacterium glutamicum. For the first time a
      fast method for metabolic screening that can be automated is described for this
      organism. More than 1000 compounds could be detected per experiment, ca. 330 of
      those showed a peak area significantly above background. Out of these 164
      compounds were identified so far, representing derivatives of 121 different
      metabolites, which were quantified in one sample. In spite of the different
      chemical nature of metabolites and high matrix content, a measurement
      reproducibility in the range of 6% error was achieved. The application of this
      method for the analysis of the adaptation of C. glutamicum to different growth
      conditions is demonstrated.

PMID- 15493882
TI  - Mechanism of the Stoddart-Heath bistable rotaxane molecular switch.
AB  - We use quantum mechanics to characterize the structure and current-voltage
      performance of the Stoddart-Heath rotaxane-based programmable electronic switch.
      We find that the current when the ring is on the DNP is 37-58 times the current
      when the ring is on the TTF, in agreement with experiment (ratio of 10-100). This
      establishes the basis for iterative experimental-theoretical efforts to optimize
      systems for molecule-based electronics which we illustrate by predicting the
      effect of adding a group such as CN to the rotaxane.

PMID- 15493883
TI  - A theoretical investigation of ruthenium-catalyzed alkene hydrosilation: evidence
      to support an exciting new mechanistic proposal.
AB  - The mechanism of ethylene hydrosilation catalyzed by the ruthenium silylene
      cation [Cp*(P(i-Pr)3)Ru(H)2(SiH2)-OEt2]+ has been investigated with B3LYP density
      functional theory. Calculations using the model cation [Cp(PH3)Ru(H)2(SiH2)
      OMe2]+ indicate that the most favorable catalytic cycle is the new mechanism
      proposed by Glaser and Tilley that involves ethylene insertion into a silicon
      hydrogen bond remote from the ruthenium center. All other pathways, including
      those based on Chalk-Harrod and modified Chalk-Harrod mechanisms that include
      ethylene coordination to ruthenium, are energetically disfavored.

PMID- 15493884
TI  - Photochemical production of nitric oxide via two-photon excitation with NIR
      light.
AB  - Herein we demonstrate the successful photochemical generation of nitric oxide via
      two-photon excitation (TPE) from the supramolecular complex PPIX-RSE ({mu-S,mu-S'
      protoporphyrin-IX-bis(2-thioethyl)diester]tetranitrosyl-diiron). The TPE
      fluorescence spectra indicate efficient energy transfer from the PPIX antennae to
      the iron sulfur nitrosyl cluster. Further evidence of NO release is demonstrated
      using a nitric oxide specific electrode and ESI+ MS.

PMID- 15493885
TI  - Synthesis of [1]rotaxane via covalent bond formation and its unique fluorescent
      response by energy transfer in the presence of lithium ion.
AB  - Although there have been a lot of reports on the synthesis and properties of
      [n]rotaxanes (mainly n = 2), only a few reports on the synthesis of [1]rotaxane
      has been published by Vogtle's group and others (see ref 5). Generally speaking,
      [1]rotaxane might be expected to exhibit properties different from other
      rotaxanes, because the rotor and the axle in the [1]rotaxane is bound covalently
      and closely. We report on a novel method to make [1]rotaxanes via covalent bond
      formation from a macrocyclic compound. That is, we first prepared a bicyclic
      compound from macrocycle and then proceeded to [1]rotaxane by aminolysis. This is
      the first synthetic example of preparation of [1]rotaxane via covalent bond
      formation, not utilizing weak interactions such as hydrogen bonding, charge
      transfer, via metal complexation, etc. This method might provide a powerful and
      new tool for construction of [1]rotaxane as a new supramolecular system. In
      addition, we investigated energy transfer from rotor to axle using [1]rotaxane
      that we prepared. Energy transfer occurred perfectly from the naphthalene ring of
      the rotor to the anthracene ring of the axle. We found also that only lithium ion
      among alkali ions can drastically enhance the fluorescence intensity. This
      finding could be applicable to ion-sensing systems, switching devices, and so on.

PMID- 15493886
TI  - Phagemid encoded small molecules for high throughput screening of chemical
      libraries.
AB  - A new strategy for monovalently displaying small molecules on phage surfaces was
      developed and applied to high throughput screening for molecules with high
      binding affinity to the target protein. Peptidyl carrier protein (PCP) excised
      from nonribosomal peptide synthetase was monovalently displayed on the surface of
      M13 phage as pIII fusion proteins. Small molecules of diverse structures were
      conjugated to coenzyme A (CoA) and then covalently attached to the phage
      displayed PCP by Sfp phosphopantetheinyl transferase. Because Sfp is broadly
      promiscuous for the transfer of small molecule linked phosphopantetheinyl
      moieties to apo PCP domains, this approach will enable displaying libraries of
      small molecules on phage surfaces. Unique 20-base-pair (bp) DNA sequences were
      also incorporated into the phagemid DNA so that each compound displayed on the
      phage surface was encoded by a DNA bar code encapsulated inside the phage coat
      protein. Single round selection of phage displayed small molecules achieved more
      than 2000-fold enrichment of small molecules with nM binding affinity to the
      target protein. The selection process is further accelerated by the use of DNA
      decoding arrays for identifying the selected small molecules.

PMID- 15493887
TI  - Monolayer-controlled substrate selectivity using noncovalent enzyme-nanoparticle
      conjugates.
AB  - Electrostatic interactions were used to noncovalently conjugate chymotrypsin to
      gold nanoparticles featuring hybrid tetraethylene(glycol)alkanethiol monolayers
      terminated with carboxylate groups. This conjugation process greatly alters the
      substrate selectivity of the adsorbed chymotrypsin, inhibiting the hydrolysis of
      anionic subtrates without affecting the hydrolysis rate of cationic analogues.

PMID- 15493888
TI  - Reaction of CO with molecularly chemisorbed oxygen on TiO2-supported gold
      nanoclusters.
AB  - In this study we present results of an investigation into the reactivity of
      molecularly chemisorbed oxygen species on a Au/TiO2 model catalyst. We have
      previously shown that a Au/TiO2 model catalyst sample can be populated with both
      atomically and molecularly chemisorbed oxygen species following exposure to a
      radio frequency-generated oxygen plasma-jet. To test the reactivity of the
      molecularly chemisorbed oxygen species, we compare the CO2 produced from a sample
      that is populated with both oxygen species to the CO2 produced from a sample that
      has been given an identical exposure but has been cleared of molecularly
      chemisorbed oxygen employing collision-induced desorption. We observe that
      samples that are populated with both oxygen species consistently result in
      greater CO2 production. For the data presented in this paper, we observe a
      difference of 41% in the CO2 production. We interpret this result to indicate
      that molecularly chemisorbed oxygen can react directly with CO to form CO2.

PMID- 15493889
TI  - On the nature of dendrimer cross-linking by ring-closing metathesis.
AB  - The ring-closing metathesis (RCM) mediated cross-linking of dendrimer 1 and it
      subunits was examined. Through the combined use of MALDI-MS-TOF, SEC, NMR, and X
      ray crystallographic analysis it was shown that the cross-links are formed with
      the following order of preference: type d >/= type c > type b > type a.

PMID- 15493890
TI  - An atomic mutation cycle for exploring RNA's 2'-hydroxyl group.
AB  - The 2'-hydroxyl group fulfills numerous structural and functional roles in RNA,
      including those of hydrogen bond donor and acceptor. While loss of function upon
      2'-deoxynucleotide substitution establishes the importance of specific 2'
      hydroxyl groups within RNA, this approach provides no information about how these
      hydroxyl groups impart their functional contribution. We use an atomic mutation
      cycle to evaluate the functional importance of the 2'-hydroxyl group's hydrogen
      atom. Using the Tetrahymena ribozyme reaction, we challenge the cycle to expose
      the catalytic contribution of the cleavage site 2'-hydroxyl group and its
      associated hydrogen bond network. The results establish the viability of this
      cycle as an approach to reveal 2'-hydroxyl groups that donate functionally
      significant hydrogen bonds.

PMID- 15493891
TI  - Optically switchable liquid crystal photonic structures.
AB  - Photo-optic materials offer the possibility of light controlled photonic devices,
      intelligent and environmentally adaptive optical materials. One strategy for
      creating these materials is the combination of structure formation through
      holographic photopolymerization and the variable optical properties of liquid
      crystals. Holographically patterned, polymer stabilized liquid crystals (HPSLCs)
      have proven to be useful optical materials. By incorporating photo-optic,
      azobenzene-derived liquid crystal blends into such material systems, we have
      generated practical photoresponsive optical materials.

PMID- 15493892
TI  - Synthesis of a calix[4]arene derivative for isolation of a stable cation radical
      salt for use as a colorimetric sensor of nitric oxide.
AB  - We have designed and synthesized a modified calixarene derivative (1) that
      allows, for the first time, the isolation of a stable cation radical salt that
      binds a single molecule of nitric oxide deep within its cavity with remarkable
      efficiency (KNO >108 M-1), as demonstrated by isolation of a crystalline complex
      [1, NO]+ and its characterization by X-ray crystallography as well as by optical
      spectroscopy. Furthermore, the ready accessibility of the calixarene cation
      radical will allow the exploration of its use for developing efficient sensing
      devices for nitric oxide based on the accompanied color changes.

PMID- 15493893
TI  - C2-symmetric bicyclo[2.2.2]octadienes as chiral ligands: their high performance
      in rhodium-catalyzed asymmetric arylation of N-tosylarylimines.
AB  - Asymmetric synthesis of diarylmethylamines with high enantioselectivity (95-99%
      ee) was realized by use of a new C2-symmetric diene ligand, (1R,4R)-2,5
      diphenylbicyclo[2.2.2]octa-2,5-diene (Ph-bod*), for the rhodium-catalyzed
      asymmetric arylation of N-tosylarylimines with arylboroxines.

PMID- 15493894
TI  - Formation of a stable 14-helix in short oligomers of furanoid cis-beta-sugar
      amino acid.
AB  - Oligomers of a new class of sugar amino acids (SAA) using a xylofuranoic acid has
      been shown to generate a robust 14-helix. The design involved the use of
      xylofuranose with a cis arrangement between the amine and carboxyl groups to
      promote the adoption of a 14-helix instead of a mixed 12/10-helix observed in a
      sugar oligomer using a ribofuranoic acid and beta-Ala. The observation of a
      stable right-handed 14-helix in a cis-SAA is unprecedented.

PMID- 15493895
TI  - Cyclodextrin-initiated polymerization of cyclic esters in bulk: formation of
      polyester-tethered cyclodextrins.
AB  - Cyclodextrins were found to initiate ring-opening polymerization of some cyclic
      esters selectively to give a polyester with a CD at the chain end.

PMID- 15493896
TI  - Ambient temperature plastic crystal electrolyte for efficient, all-solid-state
      dye-sensitized solar cell.
AB  - Doping the molecular plastic crystal of succinonitrile with solid N-methyl-N
      butylpyrrolidinium iodide salt and iodine has produced a highly conductive solid
      iodide/triiodide conductor. Furthermore, it was employed for a highly efficient,
      all-solid-state dye-sensitized solar cell.

PMID- 15493897
TI  - Synthetic multifunctional pores with external and internal active sites for
      ligand gating and noncompetitive blockage.
AB  - Design, synthesis, and multifunctionality of p-octiphenyl beta-barrel pores with
      external LRL triads and internal HH dyads are described. Molecular recognition of
      anionic fullerenes > calixarenes > pyrenes by guanidinium arrays at the outer
      pore surface is shown to result in pore opening, whereas alpha-helix recognition
      within the topologically matching internal space is shown to result in
      noncompetitive pore blockage. This experimental evidence for multifunctionality
      is supported by comparison with pertinent control pores and blockers, by
      structural studies using FRET from p-octiphenyl donors in the pore to BODIPY
      acceptors in the bilayer, and by molecular mechanics simulations. Practical
      usefulness of ligand-gated synthetic multifunctional pores is exemplified with
      the continuous detection of chemical processes.

PMID- 15493898
TI  - An organometallic inhibitor for glycogen synthase kinase 3.
AB  - Replacing natural products with kinetically inert metal complexes may lead to a
      new class of therapeutics in which a metal center plays the role of an innocent
      bystander, organizing the orientation of the organic ligands in the receptor
      space. As an example of this approach, a ruthenium complex is described that
      copies the binding mode of indolocarbazole protein kinase inhibitors and serves
      as a reversible, low-nanomolar inhibitor for glycogen synthase kinase 3 (GSK-3).

PMID- 15493899
TI  - Direct functionalization of arenes by primary alcohol sulfonate esters catalyzed
      by gold(III).
AB  - Alkylation of arenes by primary alcohol triflate or methanesulfonate esters can
      be efficiently catalyzed by AuCl3 with silver triflate.

PMID- 15493900
TI  - Unprecedented reversible migration of amide to schiff base ligands attached to
      tin: latent single-site initiators for lactide polymerization.
AB  - In an unprecedented transformation, amide ligands are found to attack the imine
      carbon centers of tridentate Schiff base ligands attached to tin. The process is
      reversible, and the resultant (masked) amide species can be exploited as latent
      single-site initiators for the controlled polymerization of rac-lactide.

PMID- 15493901
TI  - Synthesis of diastereomerically and enantiomerically pure 2,3-disubstituted
      tetrahydrofurans using a sulfoxonium ylide.
AB  - Nucleophilic substitution reactions of 2,3-epoxy alcohols, easily prepared via
      Sharpless asymmetric epoxidation chemistry, offer access to a wide variety of
      enantiomerically pure compounds. In this communication, we describe the use of a
      Payne rearrangement to control regioselectivity in the ring-opening of a series
      of 2,3-epoxy alcohols with dimethylsulfoxonium methylide to yield
      diastereomerically and/or enantiomerically pure disubstituted tetrahydrofuran
      rings. The factors influencing the success and substitution pattern of the THF
      ring products are discussed, including steric, electronic, and solvent effects.

PMID- 15493902
TI  - Effects of lipid chain lengths in alpha-galactosylceramides on cytokine release
      by natural killer T cells.
AB  - Glycolipid presentation by CD1 proteins has emerged as an important aspect of
      antigen recognition, and presentation of alpha-glycosylceramides by CD1d to
      natural killer T cells has become a central focus in understanding how glycolipid
      presentation can influence immune responses. An alpha-galactosylceramide
      containing relatively long lipid chains has been the subject of intense study
      because, when presented by CD1d to natural killer T cells, it stimulates the
      release of both proinflammatory and immunomodulatory cytokines. Using an
      efficient synthesis of alpha-galactosylceramides, we have prepared a series of
      glycolipids in which the lipid chain lengths have been incrementally varied. The
      responses of natural killer T cells to these glycolipids have been determined,
      and we have found that truncation of the phytosphingosine lipid chain increases
      the relative amounts of immunomodulatory cytokines released. In similar fashion,
      the length of the acyl chain in alpha-galactosylceramides influences cytokine
      release profiles.

PMID- 15493903
TI  - Remote asymmetric induction with vinylketene silyl n,o-acetal.
AB  - A highly regio- and diastereoselective TiCl4-mediated vinylogous Mukaiyama aldol
      reaction using the chiral vinylketene silyl N,O-acetal has been developed. The
      present vinylogous Mukaiyama aldol reaction provides a unique and effective means
      of controlling remote asymmetric induction. The methyl group at the alpha
      position is important in achieving a high level of stereoselectivity. From a
      synthetic point of view, this methodology can provide a one-step construction of
      delta-hydroxy-alpha,gamma-dimethyl-alpha,beta-unsaturated carbonyl unit that is
      seen in many natural polyketide products.

PMID- 15493904
TI  - Three-component condensation leading to beta-amino acid diamides: convergent
      assembly of beta-peptide analogues.
AB  - A Passerini condensation of acyl cyanides, carboxylic acids, and isonitriles has
      been developed that affords efficient access to functionalized diamides as well
      as beta-peptides of alpha-hydroxy-beta-amino acids. Such compounds are protease
      resistant and form stable helical and sheet structures when incorporated into
      larger peptides. N-Protected alpha-amino acids and isocyanoesters derived from
      alpha-amino acids participate in the condensation, leading to alpha/beta peptides
      embodying the heterogeneous alpha/beta/alpha backbone motif, recent examples of
      which display antibiotic activity.

PMID- 15493905
TI  - Highly enantio- and diastereoselective one-pot synthesis of acyclic epoxy
      alcohols with three contiguous stereocenters.
AB  - Two highly enantio- and diastereoselective one-pot procedures for the synthesis
      of epoxy alcohols with up to three contiguous stereocenters are reported. Route
      one involves asymmetric addition of an alkylzinc reagent to an enal followed by
      diastereoselective epoxidation. Route two entails asymmetric vinylation of an
      aldehyde with divinylzinc reagents and subsequent diastereoselective epoxidation.
      The oxidant for the epoxidation is generated by exposure of the allylic alkoxide
      intermediate and the remaining organozinc reagent to dioxygen. Upon addition of
      catalytic titanium tetraisopropoxide, the directed epoxidation yields the epoxy
      alcohols with good to excellent yields.

PMID- 15493906
TI  - Chemistry of the phosphinidene oxide ligand.
AB  - Reaction of [Mo2Cp2(mu-H)(mu-PHR*)(CO)4] with DBU followed by O2 gives the first
      anionic phosphinidene oxide complex (H-DBU)[MoCp{P(O)R*}(CO)2] (1) (DBU = 1,8
      diazabicyclo [5.4.0] undec-7-ene; R* = 2,4,6-C6H2tBu3). This anion displays three
      different nucleophilic sites located at the O, P, and Mo atoms, as illustrated by
      the reactions reported. Thus, reaction of 1 with excess HBF4.OEt2 gave the
      fluorophosphide complex [MoCp(PFR*)(CO)2] via the hidroxophosphide intermediate
      [MoCp{PR*(OH)}(CO)2]. Related alkoxyphosphide compounds [MoCp{P(OR)R*}(CO)2] (R =
      Me, C(O)Ph) were prepared by reaction of 1 with [Me3O]BF4 and PhC(O)Cl,
      respectively, whereas reaction of 1 with MeI or C3H5Br gave the P,O-bound
      phosphinite complexes [MoCp(kappa2-OPRR*)(CO)2] (R = Me, C3H5). Metal-based
      electrophiles were found to bind at either O or Mo positions. Thus, reaction of 1
      with [ZrCl2Cp2] gave the phosphinidene oxide bridged [MoCp{P(OZrClCp2)R*}(CO)2],
      whereas reaction with SnPh3Cl gave trans-[MoCp{P(O)R*}(CO)2(SnPh3)], an
      heterometallic complex having an intact terminal P(O)R* ligand.

PMID- 15493907
TI  - Supramolecular nanocarrier of siRNA from PEG-based block catiomer carrying
      diamine side chain with distinctive pKa directed to enhance intracellular gene
      silencing.
AB  - An siRNA nanocarrier formed through self-assembly of PEG-based block catiomer
      possessing two distinct amino groups with different pKa values in a side chain
      was developed. This design provided the carrier with a sufficient siRNA
      complexation and an assumed buffering capacity in the endosomes, allowing it to
      exhibit remarkable gene knockdown abilities as well as sufficient serum
      tolerability.

PMID- 15493908
TI  - Ruthenium-catalyzed hydrogenation of alkynylstannanes with migration of the
      stannyl group.
AB  - Molecular hydrogen adds to aliphatic and aromatic alkynylstannanes in the
      presence of a ruthenium catalyst, pushing the stannyl group to the adjacent
      carbon atom to give alpha-substituted vinylstannanes. This is the first
      achievement of hydrogenation of alkynylstannanes, which is applicable also to the
      deuteration affording precursors for an important class of deuterium-labeled
      compounds.

PMID- 15493909
TI  - De novo designed peptidic redox potential probe: linking sensitized emission to
      disulfide bond formation.
AB  - The design and utility of a peptidic probe capable of accurately measuring
      environmental redox potential via sensitized emission has been prepared. This
      probe is characterized by long-lived luminescence (millisecond), nanomolar
      detection limits, and a probe reduction potential of -0.243 V.

PMID- 15493910
TI  - Alkene-alkyne coupling as a linchpin: an efficient and convergent synthesis of
      amphidinolide P.
AB  - A short and efficient synthesis of the cytotoxic macrolide amphidinolide P is
      described. A remarkably chemo- and regioselective ruthenium-catalyzed alkene
      alkyne coupling allows for a convergent synthesis and demonstrates that both
      enynes and beta-lactones are suitable coupling partners. This work also features
      a novel strategy for the preparation of macrolactones via intramolecular
      transesterification of beta-lactones. The target structure was prepared in 15
      steps for the longest linear sequence and 10% overall yield, 24 steps total.

PMID- 15493911
TI  - A biomimetic approach to the rocaglamides employing photogeneration of
      oxidopyryliums derived from 3-hydroxyflavones.
AB  - A unified biomimetic approach to the aglain-forbaglin-rocaglamide classes of
      natural products is reported. The approach involves photogeneration of
      oxidopyryliums via excited-state intramolecular proton transfer (ESIPT) of 3
      hydroxyflavones followed by [3+2] dipolar cycloaddition to the aglain core. An
      alpha-ketol (acyloin) rearrangement was employed to transform the aglain core to
      the rocaglamide framework. This approach was successfully used for the synthesis
      of the natural product (+/-)-methyl rocaglate.

PMID- 15493912
TI  - Dirhodium(II) caprolactamate: an exceptional catalyst for allylic oxidation.
AB  - The oxidation of organic molecules represents a fundamentally important chemical
      process. Particularly important is allylic oxidation, whereby a single methylene
      unit is converted directly into a carbonyl group. In this communication, we
      report that dirhodium(II) caprolactamate [Rh2(cap)4] in combination with tert
      butyl hydroperoxide (terminal oxidant) effectively catalyzes the allylic
      oxidation of a variety of olefins and enones. The reaction is completely
      selective, tolerant of air/moisture, and can be performed with as little as 0.1
      mol % catalyst in minutes. A mechanistic proposal involving redox chain catalysis
      has been put forth, as well as evidence for the intermediacy of a higher valent
      dirhodium tert-butyl peroxy complex.

PMID- 15493913
TI  - Carbon and SiC macroscopic beads from ion-exchange resin templates.
AB  - A method for preparing carbon and SiC macroscopic beads using ion-exchange resins
      as a macrotemplate that determines the macroshape and the pore structure of the
      product materials is reported. First, silicates are ion-exchanged into the resins
      to prevent the resin from collapsing during subsequent carbonization and allow
      them to be used as precursors for SiC formation. SiC is prepared via carbothermal
      reduction of carbon/silica composite beads obtained upon carbonization of the
      resin/silicate in an inert atmosphere. Finally, silica is removed by HF etching.
      Very high-surface area (1670-2026 m2 g-1) micro- or micro-/mesoporous carbon
      beads and relatively high-surface area (35-63 m2 g-1) macro- and meso
      /macroporous SiC beads were prepared by the described method. The pore structure
      and the macroshape of the particles were controlled by the type of ion-exchange
      resins employed, gel or macroreticular.

PMID- 15493914
TI  - Copper(II)-quenched oligonucleotide probes for fluorescent DNA sensing.
AB  - A copper(II)-quenched molecular beacon was prepared by attaching fluorescein to
      the 3'-end and a copper(II) complex to the 5'-end of DNA. In the presence of
      complementary DNA, copper(II) and dye are spatially separated in the duplex and
      fluorescence increases up to 15-fold, with excellent discrimination of single
      base mismatches.

PMID- 15493915
TI  - Iron complexes of (e)- and (z)-1,2-dichlorodisilenes.
AB  - Novel disilene-iron complexes [(E)- (1E) and (Z)-(eta2-R3SiClSi=SiClSiR3)Fe(CO)4
      (1Z), SiR3 = tBu2MeSi] were synthesized by the reaction of the corresponding
      tetrachlorodisilane with an excess amount of K2Fe(CO)4, and the structures of 1E
      and 1Z were determined by X-ray crystallography. These complexes constitute not
      only the first transition-metal complexes with E,Z-isomerism but also the first
      complexes with halogen-substituted disilene ligands. The initial formation of 1Z
      during the synthetic reaction and the slow one-way isomerization of 1Z to 1E are
      rationalized by the intervention of the corresponding silylene complex
      (R3SiCl2Si)(R3Si)Si=Fe(CO)4.

PMID- 15493916
TI  - Orientational control of electronic coupling in mixed-valence, binuclear
      ruthenium(II)-bis(2,2':6',2' '-terpyridine) complexes.
AB  - A series of binuclear ruthenium(II)-bis(2,2':6',2' '-terpyridine) complexes has
      been prepared around a central biphenylene unit equipped with a strap of variable
      length. Partial oxidation forms the mixed-valence complex that displays both
      ligand-to-metal, charge-transfer, and intervalence charge-transfer (IVCT)
      transitions in the near-IR region. On the basis of Hush theory, the electronic
      coupling matrix element for interaction between the metal centers decreases with
      increasing length of the tethering strap. This effect arises because the strap
      modulates the torsion angle between the phenyl rings and thereby controls the
      extent of through-bond electronic coupling. The coupling element favors a maximum
      for planar geometries and a minimum for orthogonal structures, but the full
      impact of the torsion angle is not realized due to thermal fluctuations.

PMID- 15493917
TI  - Cooperative catalysis of a cationic ruthenium complex, amine base, and na salt:
      catalytic activation of acetonitrile as a nucleophile.
AB  - Cooperative catalysis of a cationic Ru complex, DBU, and NaPF6 is described. An
      exquisite combination of the catalytic triad enabled catalytic activation of
      acetonitrile as a nucleophile under mild amine-basic conditions. Addition of in
      situ-generated, Ru-bound, metalated nitrile to aldehydes and imines proceeded
      smoothly with 2.5-5 mol % Ru complex and 2.5-10 mol % DBU in the presence of 10
      mol % NaPF6. Preliminary mechanistic studies suggested a role for each of the
      three catalytic components.

PMID- 15493918
TI  - The dithianyl group as a synthon in porphyrin chemistry: condensation reactions
      and preparation of formylporphyrins under basic conditions.
AB  - Vilsmeier formylation is one of the most widely used substitution reactions for
      the functionalization of porphyrins. However, its utility is limited by the
      electrophilic/acidic reaction conditions, deactivation of the aromatic system and
      regiochemical problems, the requirement for metal complexes and necessity for
      subsequent demetalation under harsh conditions, and low functional group
      tolerance. To overcome these limitations, the dithianyl group has been utilized
      as a latent formyl synthon in porphyrin chemistry. 2-Formyl-1,3-dithiane can be
      used directly in pyrrole condensation reactions to regioselectively yield
      porphyrins with up to four dithianyl residues. Likewise, 5
      dithianyldipyrromethane could be prepared quantitatively as a key building block
      for various porphyrin condensation reactions yielding the respective free base
      formylporphyrins after deprotection. Additionally, dithianyllithium can be used
      as a reagent for the direct aromatic substitution of metallo- and free base
      porphyrins under nucleophilic conditions.

PMID- 15493919
TI  - Glycosidic torsional motions in a bicelle-associated disaccharide from residual
      dipolar couplings.
AB  - An analysis of torsional motions about glycosidic bonds in a disaccharide is
      undertaken using residual dipolar coupling measurements and selective
      immobilization of the reducing end sugar to provide a suitable motional
      reference. The immobilization is accomplished by using the short chain of an
      alkyl glycoside to anchor the disaccharide to a bilayer medium aligned in
      magnetic field. Motions about the beta-(1-4) linkage of the n-butyl-4-O-beta-d
      galactopyranosyl-alpha-d-mannopyranoside are shown to be substantial (+/-40
      degrees ) and in good agreement with predictions of a fully solvated molecular
      dynamics simulation.

PMID- 15493920
TI  - Control of protein adsorption: molecular level structural and spatial variables.
AB  - The adsorption of fibrinogen (Fb) and bovine serum albumin onto polycrystalline
      Au coated with HS(CH2)3O(CH2CH2O)5CH3 was determined by surface plasmon resonance
      from bare Au (0% coverage) to the complete ( approximately 100% coverage) self
      assembled monolayer (SAM). Both proteins exhibit similar adsorption curves with
      common onset ( approximately 60% coverage) and range ( approximately 60% to 80%
      coverage) of minimal protein adsorption. Reflection-absorption infrared
      spectroscopic data show that widespread order is not present in the films over
      this range of coverage, indicating loosely packed, bound oligomers that are
      uniformly distributed and fully screen the underlying substrate. On the basis of
      our data, we propose a mechanism of protein rejection by oligo(ethylene oxide)
      (OEO)-modified surfaces in terms of changes in free energy (DeltaGsystem; system
      = protein + surface) due to oligomer conformational constriction over an area
      greater than the contact area. Minimal protein adsorption corresponds to the
      maximum DeltaGsystem for a given compression. This controlled study of protein
      adsorption provides insights into the molecular level understanding of protein
      adsorption unavailable from previous polymer and comparative SAM studies.

PMID- 15493921
TI  - Origins of cell selectivity of cationic steroid antibiotics.
AB  - A key factor in the potential clinical utility of membrane-active antibiotics is
      their cell selectivity (i.e., prokaryote over eukaryote). Cationic steroid
      antibiotics were developed to mimic the lipid A binding character of polymyxin B
      and are shown to bind lipid A derivatives with affinity greater than that of
      polymyxin B. The outer membranes of Gram-negative bacteria are comprised
      primarily of lipid A, and a fluorophore-appended cationic steroid antibiotic
      displays very high selectivity for Gram-negative bacterial membranes over Gram
      positive bacteria and eukaryotic cell membranes. This cell selectivity of
      cationic steroid antibiotics may be due, in part, to the affinity of these
      compounds for lipid A.

PMID- 15493922
TI  - QM/MM studies of the enzyme-catalyzed dechlorination of 4-chlorobenzoyl-CoA
      provide insight into reaction energetics.
AB  - The conversion of 4-chlorobenzoyl-CoA to 4-hydroxybenzoyl-CoA catalyzed by 4
      chlorobenzoyl-CoA dehalogenase is investigated using combined QM/MM approaches.
      The calculated potential of mean force at the PM3/CHARMM level supports the
      proposed nucleophilic aromatic substitution mechanism. In particular, a
      Meisenheimer intermediate was found, stabilized by hydrogen bonds between the
      benzoyl carbonyl of the ligand and two backbone amide NHs at positions 64 and
      114. Mutation of Gly113 to Ala significantly increases the barrier by disrupting
      the hydrogen bond with the Gly114 backbone. The formation of the Meisenheimer
      complex is accompanied by significant charge redistribution and structural
      changes in the substrate benzoyl moiety, consistent with experimental
      observations. Theoretical results suggest that the reaction rate is limited by
      the formation of the Meisenheimer complex, rather than by its decomposition. A
      kinetic model based on the calculated free energy profile is found to be
      consistent with the experimental time course data.

PMID- 15493923
TI  - Thiophene-based diamidine forms a "super" at binding minor groove agent.
AB  - The DNA minor groove is the interaction site for many enzymes and transcription
      control proteins and as a result, development of compounds that target the minor
      groove is an active research area. In an effort to develop biologically active
      minor groove agents, we are preparing and exploring the DNA interactions of a
      systematic set of diamidine derivatives with a powerful array of methods
      including DNase I footprinting, biosensor-SPR methods, and X-ray crystallography.
      Surprisingly, conversion of the parent phenyl-furan-phenyl diamidine to a phenyl
      thiophene-benzimidazole derivative yields a compound with over 10-fold-increased
      affinity for the minor groove at AT sequences. Single conversion of the furan to
      a thiophene or a phenyl to benzimidazole does not cause a similar increase in
      affinity. X-ray results indicate a small bond angle difference between the C-S-C
      angle of thiophene and the C-O-C angle of furan that, when amplified out to the
      terminal amidines of the benzimidazole compounds, yields a very significant
      difference in the positions of the amidines and their DNA interaction strength.

PMID- 15493924
TI  - Thermodynamic characterization of the binding of tetrahydropterins to
      phenylalanine hydroxylase.
AB  - Phenylalanine hydroxylase (PAH) is the key enzyme in the catabolism of L-Phe. The
      natural cofactor of PAH, 6R-tetrahydrobiopterin (BH4), negatively regulates the
      enzyme activity in addition to being an essential cosubstrate for catalysis. The
      analogue 6-methyltetrahydropterin (6M-PH4) is effective in catalysis but does not
      regulate PAH. Here, the thermodynamics of binding of BH4 and 6M-PH4 to human PAH
      have been studied by isothermal titration calorimetry. At neutral pH and 25
      degrees C, BH4 binds to PAH with higher affinity (Kd = 0.75 +/- 0.18 microM) than
      6M-PH4 (Kd = 16.5 +/- 2.7 microM). While BH4 binding is a strongly exothermic
      process (DeltaH = -11.8 +/- 0.4 kcal/mol) accompanied by an entropic penalty (
      TDeltaS = 3.4 +/- 0.4 kcal/mol), 6M-PH4 binding is both enthalpically (DeltaH = 
      3.3 +/- 0.3 kcal/mol) and entropically (-TDeltaS = -3.2 kcal/mol) driven. No
      significant changes in binding affinity were observed in the 5-35 degrees C
      temperature range for both pterins at neutral pH, but the enthalpic contribution
      increased with temperature rendering a heat capacity change (DeltaCp) of -357 +/-
      26 cal/mol/K for BH4 and -63 +/- 12 cal/mol/K for 6M-PH4. Protons do not seem to
      be taken up or released upon pterin binding. Structure-based energetics
      calculations applied on the molecular dynamics simulated structures of the
      complexes suggest that in the case of BH4 binding, the conformational
      rearrangement of the N-terminal tail of PAH contribute with favorable enthalpic
      and unfavorable entropic contributions to the intrinsic thermodynamic parameters
      of binding. The entropic penalty is most probably associated to the reduction of
      conformational flexibility at the protein level and disappears for the L-Phe
      activated enzyme. The calculated energetic parameters aid to elucidate the
      molecular mechanism for cofactor recognition and the regulation of PAH by the
      dihydroxypropyl side chain of BH4.

PMID- 15493925
TI  - The helical alanine controversy: an (Ala)6 insertion dramatically increases
      helicity.
AB  - Employing chemical shift melts and hydrogen/deuterium exchange NMR techniques, we
      have determined the stabilization of the Trp-cage miniprotein due to multiple
      alanine insertions within the N-terminal alpha-helix. Alanine is shown to be
      uniquely helix-stabilizing and this stabilization is reflected in the global fold
      stability of the Trp-cage. The associated free energy change per alanine can be
      utilized to calculate the alanine propagation value. From the Lifson-Roig
      formulation, the calculated value (wAla = 1.6) is comparable to those obtained
      for short, solubilized, alanine-rich helices and is much larger than the values
      obtained by prior host-guest techniques or in N-terminally templated helices and
      peptides bearing long contiguous strings of alanines with no capping or
      solubilizing units present.

PMID- 15493926
TI  - Amplified quenching of a conjugated polyelectrolyte by cyanine dyes.
AB  - The conjugated polyelectrolyte PPESO3 features a poly(phenylene ethynylene)
      backbone substituted with anionic 3-sulfonatopropyloxy groups. PPESO3 is quenched
      very efficiently (KSV > 10(6) M(-1)) by cationic energy transfer quenchers in an
      amplified quenching process. In the present investigation, steady-state and
      picosecond time-resolved fluorescence spectroscopy are used to examine amplified
      quenching of PPESO3 by a series of cyanine dyes via singlet-singlet energy
      transfer. The goal of this work is to understand the mechanism of amplified
      quenching and to characterize important parameters that govern the amplification
      process. Steady-state fluorescence quenching of PPESO3 by three cationic
      oxacarbocyanine dyes in methanol solution shows that the quenching efficiency
      does not correlate with the Forster radius computed from spectral overlap of the
      PPESO3 fluorescence with the cyanines' absorption. The quenching efficiency is
      controlled by the stability of the polymer-dye association complex. When
      quenching studies are carried out in water where PPESO3 is aggregated, changes
      observed in the absorption and fluorescence spectra of 1,1',3,3,3',3'
      hexamethylindotricarbocyanine iodide (HMIDC) indicate that the polymer templates
      the formation of a J-aggregate of the dye. The fluorescence dynamics in the
      PPESO3/HMIDC system were probed by time-resolved upconversion and the results
      show that PPESO3 to HMIDC energy transfer occurs on two distinctive time scales.
      At low HMIDC concentration, the dynamics are dominated by an energy transfer
      pathway with a time scale faster than 4 ps. With increasing HMIDC concentration,
      an energy pathway with a time scale of 0.1-1 ns is active. The prompt pathway
      (tau < 4 ps) is attributed to quenching of delocalized PPESO3 excitons created
      near the HMIDC association site, whereas the slow phase is attributed to intra-
      and interchain exciton diffusion to the HMIDC.

PMID- 15493927
TI  - Synthesis and properties of monodisperse oligofluorene-functionalized truxenes:
      highly fluorescent star-shaped architectures.
AB  - This paper describes the strategy toward novel monodisperse, well-defined, star
      shaped oligofluorenes with a central truxene core and from monofluorene to
      quaterfluorene arms. Introduction of solubilizing n-hexyl groups at both fluorene
      and truxene moieties results in highly soluble, intrinsically two-dimensional
      nanosized macromolecules T1-T4. The radius for the largest oligomer of ca. 3.9 nm
      represents one of the largest known star-shaped conjugated systems. Cyclic
      voltammetry experiments reveal reversible or quasi-reversible oxidation and
      reduction processes (Eox = +0.74 to 0.80 V, Ered = -2.66 to 2.80 eV vs Fc/Fc+),
      demonstrating excellent electrochemical stability toward both p- and n-doping,
      while the band gaps of the oligomers are quite high (EgCV = 3.20-3.40 eV). Close
      band gaps of 3.05-3.29 eV have been estimated from the electron absorption
      spectra. These star-shaped macromolecules demonstrate good thermal stability (up
      to 400-420 degrees C) and improved glass transition temperatures with an increase
      in length of the oligofluorene arms (from Tg = 63 degrees C for T1 to 116 degrees
      C for T4) and show very efficient blue photoluminescence (lambdaPL = 398-422 nm)
      in both solution (PhiPL = 70-86%) and solid state (PhiPL = 43-60%).
      Spectroelectrochemical experiments reveal that compounds T1-T4 are stable
      electrochromic systems which change their color reversibly from colorless in the
      neutral state (approximately 340-400 nm) to colored (from red to purple color;
      approximately 500-600 nm) in the oxidized state.

PMID- 15493928
TI  - A new rearrangement process in tert-amyl cation.
AB  - 13C NMR spectroscopy of the 2-methyl-2-butyl-1-13C cation (13C-labeled tert-amyl
      cation) indicates that interchange of the inside and outside carbons occurs via a
      barrier of 19.5 +/- 2.0 kcal/mol. A plausible mechanism involves hydride
      migration in the proposed 2-pentyl cation 4 to form 3-pentyl cation 5. Via the
      protonated cyclopropane intermediate 6, which undergoes degenerate corner-to
      corner hydride shift, the secondary 3-pentyl cation 5' with the label shifted to
      the central carbon atom is formed. The tert-amyl cation obtained from 5' in the
      reverse process has the 13C label on an inside carbon atom. All intermediates and
      transition structures were located on the PES theoretically at the MP2/6-31G(d,p)
      level of theory. The rearrangement rate of the doubly labeled tert-amyl cation
      (methyl-13C-butyl-1-13C cation), followed by means of 13C NMR, revealed that the
      process that interchanges inside and outside carbons has the highest barrier.
      Comparison of the initial rates revealed that isotopomer 1e arises considerably
      more slowly than other isotopomers, indicating that in the overall rearrangement
      process transition structure 5-TS has the highest energy.

PMID- 15493929
TI  - Application of chiral cationic catalysts to several classical syntheses of
      racemic natural products transforms them into highly enantioselective pathways.
AB  - This paper describes the application of chiral oxazaborolidinium cations of type
      2 to various enantioselective Diels-Alder reactions that have served as early key
      steps for the syntheses of complex natural products. In the original syntheses
      these Diels-Alder reactions produced racemic adducts and led to racemic target
      molecules unless a separation of enantiomers by classical resolution was
      employed. By use of chiral catalysts of type 2, chiral products were obtained
      directly from Diels-Alder reactions of achiral components in excellent yield and
      enantioselectivity and with the mechanistically predicted absolute configuration.
      As a result, a number of classical syntheses could be converted to
      enantioselective versions, including (1) cortisone/cortisol (Merck/Sarett), (2)
      dendrobine (Kende), (3) vitamin B(12) (Eschenmoser), (4) myrocin C (Chu
      Moyer/Danishefsky), (5) coriolin and hirsutene (Mehta), (6) dendrobatid 251F
      (Aube), (7) silphinene (Ito), and (8) nicandrenone core (Stoltz/Corey).

PMID- 15493930
TI  - Calix[4]phyrins. Effect of peripheral substituents on conformational mobility and
      structure within a series of related systems.
AB  - A new, stepwise synthesis of calix[4]phyrins is described. It relies on the
      condensation of a ketone with pyrrole to form a dipyrromethane containing a
      quaternary carbon center that is subsequently condensed with an aromatic
      aldehyde. This methodology, in contrast to the previous rational approach
      described by this group (involving formation of a trisubstituted dipyrromethane
      via the condensation of an aldehyde with pyrrole, followed by condensation of
      this dipyrromethane with acetone), allows for a variety of bulky, ketone-derived
      substituents to be incorporated into the meso-like positions. The resulting
      systems, while all containing the same central macrocyclic core, display
      conformational properties that reflect the nature of these meso-like
      substituents; these conformational features were independently assessed by X-ray
      diffraction analysis, NMR spectroscopy, and quantum chemical calculations.

PMID- 15493931
TI  - pH-sensitive bipolar ion-permselective ultrathin films.
AB  - pH-Sensitive bipolar ion-permselective films of polyelectrolyte multilayers were
      prepared by layer-by-layer (LbL) assembly and photo-cross-linking of benzophenone
      modified poly(acrylic acid) (PAA-BP) and poly(allylamine hydrochloride) (PAH-BP).
      The multilayer structure and ionizable group composition was finely tuned by
      changing the pH of the dipping solution. This structure and composition was in
      turn "preserved" by photo-cross-linking, forming highly stable membrane films.
      Since PAA-BP and PAH-BP are weak polyelectrolytes, it is possible to control the
      number of unbound, un-ionized -COOH or -NH2 groups in the multilayer by changing
      the pH. Moreover, the pH of the deposited film also plays an important role in
      determining selective latter permselectivity. For example, PAA-BP/PAH-BP
      multilayers deposited from two pH conditions, pH = 3 (PAA-BP) and pH = 6 (PAH
      BP), showed pH-switchable permselectivity for both cationic (pH = 10) and anionic
      (pH = 3) probe molecules in a single film. The system offers advantages in film
      stability and introducing reversible selective ion permeability over previous
      multilayer film and cross-linking methods.

PMID- 15493932
TI  - Photochemical study of [3(3)](1,3,5)cyclophane and emission spectral properties
      of [3n]cyclophanes (n = 2-6).
AB  - Thephotochemical reaction of [3(3)](1,3,5)cyclophane 2, which is a photoprecursor
      for the formation of propella[3(3)]prismane 18, was studied using a sterilizing
      lamp (254 nm). Upon photolysis in dry and wet CH2Cl2 or MeOH in the presence of 2
      mol/L aqueous HCl solution, the cyclophane 2 afforded novel cage compounds
      comprised of new skeletons, tetracyclo[6.3.1.0.(2,7)0(4,11)]dodeca-5,9-diene 43,
      hexacyclo[6.4.0.0.(2,6)0.(4,11)0.(5,10)0(9,12)]dodecane 44, and
      pentacyclo[6.4.0.0.(2,6)0.(4,11)0(5,10)]dodecane 45. All of these products were
      confirmed by the X-ray structural analyses. A possible mechanism for the
      formation of these photoproducts via the hexaprismane derivative 18 is proposed.
      The photophysical properties in the excited state of the [3n]cyclophanes ([3n]CP,
      n = 2-6) were investigated by measuring the emission spectra and determining the
      quantum yields and lifetimes of the fluorescence. All [3n]CPs show excimeric
      fluorescence without a monomeric one. The lifetime of the excimer fluorescence
      becomes gradually longer with the increasing number of the trimethylene bridges.
      The [3n]CPs also shows excimeric phosphorescence spectra without vibrational
      structures for n = 2, 4, and 5, while phosphorescence is absent for n = 3 and 6.
      With an increase in symmetry of the benzene skeleton in the [3(3)]- and
      [3(6)]CPs, the probability of the radiation (phosphorescence) process from the
      lowest triplet state may drastically decrease.

PMID- 15493933
TI  - In situ disorder-order transformation in synthetic gallosilicate zeolites with
      the NAT topology.
AB  - Here, we report that synthetic gallosilicate molecular sieves with the NAT
      topology and Si/Ga ratios close to but slightly higher than 1.50 undergo an in
      situ transformation under their crystallization conditions. The materials have
      been studied ex situ by using powder X-ray diffraction, elemental and thermal
      analyses, and multinuclear MAS NMR. The transformation is characterized by a
      change in the distribution of Si and Ga of the NAT framework, from a quite (but
      not completely) disordered phase to a very highly (but not completely) ordered
      one, accompanied by a change from tetragonal to orthorhombic symmetry. During
      most of the solution-mediated transformation, no noticeable signs of fresh
      precipitation, phase segregation, or changes in the chemical composition are
      detected. Intermediate materials show variations in the degree of Si-Ga ordering
      and orthorhombic distortion and are not physical mixtures of the disordered and
      ordered phases. Ab initio calculations strongly suggest a preferential siting of
      Si in the tetrahedral sites involved in a smaller number of 4-rings in the NAT
      topology (i.e., the low multiplicity site). The cost of violations of
      Loewenstein's rule has also been calculated. For this topology and chemical
      composition the preferential siting and Loewenstein's rule drive together the
      system to the ordered configuration. A Monte Carlo sampling procedure affords a
      reasonable model for the initial, mainly disordered state, which fits well within
      the experimental disorder-order series.

PMID- 15493934
TI  - Stereoselective tandem 1,4-addition reactions for benzenes: a comparison of
      Os(II), Re(I), and W(0) systems.
AB  - The arene ligand in the complex TpRe(CO)(MeIm)(eta2-benzene) (Tp =
      hydridotris(pyrazolyl)borate; MeIm = N-methylimidazole) undergoes tandem
      electrophile/nucleophile 1,4-addition reactions. Subsequent oxidative
      demetalation affords cis-3,6-disubstituted 1,4-cyclohexadienes (46-84%). Common
      organic electrophiles such as acetals and Michael acceptors were successfully
      added to the bound benzene to generate eta3-benzenium complexes, which then were
      treated with a silyl ketene acetal, silyl vinyl ether, phenyllithium, or malonate
      ester to afford 1,4-dialkylated dihydrobenzene complexes. The d6 transition metal
      analogues TpW(NO)(PMe3)(eta2-benzene) and [Os(NH3)5(eta2-benzene)]2+ also undergo
      1,4-dialkylation reactions, and the relative ability of all three metals to
      activate arenes is compared.

PMID- 15493935
TI  - Reactivity of aqueous Fe(IV) in hydride and hydrogen atom transfer reactions.
AB  - Oxidation of cyclobutanol by aqueous Fe(IV) generates cyclobutanone in
      approximately 70% yield. In addition to this two-electron process, a smaller
      fraction of the reaction takes place by a one-electron process, believed to yield
      ring-opened products. A series of aliphatic alcohols, aldehydes, and ethers also
      react in parallel hydrogen atom and hydride transfer reactions, but acetone and
      acetonitrile react by hydrogen atom transfer only. Precise rate constants for
      each pathway for a number of substrates were obtained from a combination of
      detailed kinetics and product studies and kinetic simulations. Solvent kinetic
      isotope effect for the self-decay of Fe(IV), kH2O/kD2O = 2.8, is consistent with
      hydrogen atom abstraction from water.

PMID- 15493936
TI  - High-resolution 31p field cycling NMR as a probe of phospholipid dynamics.
AB  - We have used high-resolution field-cycling 31P NMR spectroscopy to measure spin
      lattice relaxation rates (R1 = 1/T1) of multicomponent phospholipid vesicle and
      micelle samples over a large field range, from 0.1 to 11.7 T. The shape of the
      curve for R1 as a function of field and a model-free analysis were used to
      extract tauc, a correlation time for each type of phospholipid molecule in the
      bilayer that is likely to reflect rotation of the molecule about the axis
      perpendicular to the membrane surface; Sc2, a chemical shift anisotropy (CSA)
      order parameter; and tauhf, a time constant reflecting faster internal motion.
      This 31P technique was also used to monitor association of a peripheral membrane
      protein, Bacillus thuringiensis phosphatidylinositol-specific phospholipase C,
      with both phosphatidylcholine and phosphatidylmethanol bilayers. Differences in
      phospholipid dynamics induced by the protein shed light on how zwitterionic
      phosphatidylcholine, and not the anionic phosphatidylmethanol, activates the
      enzyme toward its substrate.

PMID- 15493937
TI  - Large-scale fabrication of wafer-size colloidal crystals, macroporous polymers
      and nanocomposites by spin-coating.
AB  - This paper reports a simple spin-coating technique for rapidly fabricating three
      types of technologically important materials--colloidal crystal, macroporous
      polymer, and polymeric nanocomposite, each with high crystalline qualities and
      wafer-scale sizes. Dispersion of monodisperse silica colloids in triacrylate
      monomers is spin-coated onto a variety of substrates. Shear-induced ordering and
      subsequent polymerization lead to the formation of three-dimensionally (3D)
      ordered colloidal crystals trapped inside a polymer matrix. The thickness of as
      synthesized colloidal crystal-polymer nanocomposite is highly uniform and can be
      controlled simply by changing the spin speed and time. Selective removal of the
      polymer matrix and silica spheres lead to the formation of large-area colloidal
      crystals and macroporous polymers, respectively. The wafer-scale process is
      compatible with standard semiconductor microfabrication, as multiple micrometer
      sized patterns can be created simultaneously for potential device applications.
      Normal-incidence transmission spectra in the visible and near-infrared regions
      show distinct peaks due to Bragg diffraction from 3D ordered structures. The spin
      coating process opens a new route to the fundamental studies of shear-induced
      crystallization, melting and relaxation.

PMID- 15493938
TI  - Dopant ion size and electronic structure effects on transparent conducting
      oxides. Sc-doped CdO thin films grown by MOCVD.
AB  - A series of Sc-doped CdO (CSO) thin films have been grown on both amorphous glass
      and single-crystal MgO(100) substrates at 400 degrees C by MOCVD. Both the
      experimental data and theoretical calculations indicate that Sc3+ doping shrinks
      the CdO lattice parameters due to its relatively small six-coordinate ionic
      radius, 0.89 angstroms, vs 1.09 angstroms for Cd2+. Conductivities as high as
      18100 S/cm are achieved for CSO films grown on MgO(100) at a Sc doping level of
      1.8 atom %. The CSO thin films exhibit an average transmittance >80% in the
      visible range. Sc3+ doping widens the optical band gap from 2.7 to 3.4 eV via a
      Burstein-Moss energy level shift, in agreement with the results of band structure
      calculations within the sX-LDA (screened-exchange local density approximation)
      formalism. Epitaxial CSO films on single-crystal MgO(100) exhibit significantly
      higher mobilities (up to 217 cm2/(V x s)) and carrier concentrations than films
      on glass, arguing that the epitaxial CSO films possess fewer scattering centers
      and higher doping efficiencies due to the highly textured microstructure.
      Finally, the band structure calculations provide a microscopic explanation for
      the observed dopant size effects on the structural, electronic, and optical
      properties of CSO.

PMID- 15493939
TI  - Preparation and molecular and electronic structures of iron(0) dinitrogen and
      silane complexes and their application to catalytic hydrogenation and
      hydrosilation.
AB  - Reduction of the five-coordinate iron(II) dihalide complexes (iPrPDI)FeX2 (iPrPDI
      = ((2,6-CHMe2)2C6H3N=CMe)2C5H3N; X = Cl, Br) with sodium amalgam under 1 atm of
      dinitrogen afforded the square pyramidal, high spin iron(0) bis(dinitrogen)
      complex (iPrPDI)Fe(N2)2. In solution, (iPrPDI)Fe(N2)2 loses 1 equiv of N2 to
      afford the mono(dinitrogen) adduct (iPrPDI)Fe(N2). Both dinitrogen compounds
      serve as effective precatalysts for the hydrogenation and hydrosilation of
      olefins and alkynes. Effecient catalytic reactions are observed with low catalyst
      loadings (< or = 0.3 mol %) at ambient temperature in nonpolar media. The
      catalytic hydrosilations are selective in forming the anti-Markovnikov product.
      Structural characterization of a high spin iron(0) alkyne and a bis(silane) sigma
      complex has also been accomplished and in combination with isotopic labeling
      studies provides insight into the mechanism of both catalytic C-H and catalytic C
      Si bond formation.

PMID- 15493940
TI  - Mechanistic studies of the copolymerization reaction of aziridines and carbon
      monoxide to produce poly-beta-peptoids.
AB  - The coupling of carbon monoxide and aziridines has been shown to be selective for
      comonomer-alternating enchainment in the presence of PhCH2C(O)Co(CO)4 to afford
      poly-beta-peptoids. In this article, we have investigated the mechanistic aspects
      of the reaction of CO and N-butylaziridine by means of in situ infrared
      spectroscopy employing CH3C(O)Co(CO)3L (L = PPh3 (1) and P(o-tolyl)3 (2)) as
      precatalysts. Precatalyst 1 exists in solution under catalytic conditions as an
      equilibrium mixture of 1 and CH3C(O)Co(CO)4, and affords both poly-beta
      butylalanoid and the corresponding lactam. By way of contrast, precatalyst 2
      which possesses the sterically bulky and labile P(o-tolyl)3 ligand, affords only
      the acyl cobalt tetracarbonyl species in solution during catalysis with
      concomitant selective production of the copolymer. Kinetic studies conducted with
      precatalyst 2 showed the coupling reaction to have a first order dependence on
      catalyst, a first order dependence on N-butylaziridine, and only a slight
      dependence on the concentration of CO over the pressure range 17-69 bar. The
      working mechanistic model for the copolymerization reaction involves first
      aziridine insertion into the cobalt-acyl bond, rate determining ring opening by
      the cobaltate species, followed by the migratory CO insertion.

PMID- 15493941
TI  - Molecular architecture of nanocapsules, bilayer-enclosed solid particles of
      Cisplatin.
AB  - Cisplatin nanocapsules represent a lipid formulation of the anticancer drug cis
      diamminedichloroplatinum(II) (cisplatin) characterized by an unprecedented
      cisplatin-to-lipid ratio and exhibiting strongly improved cytotoxicity against
      tumor cells in vitro as compared to the free drug (Burger, K. N. J., et al. Nat.
      Med. 2002, 8, 81-84). Cisplatin nanocapsules are prepared by the repeated
      freezing and thawing of an equimolar dispersion of phosphatidylserine (PS) and
      phosphatidylcholine (PC) in a concentrated aqueous solution of cisplatin. Here,
      the molecular architecture of these novel nanostructures was elucidated by solid
      state NMR techniques. 15N NMR and 2H NMR spectra of nanocapsules containing 15N-
      and 2H-labeled cisplatin, respectively, demonstrated that the core of the
      nanocapsules consists of solid cisplatin devoid of free water. Magic-angle
      spinning 15N NMR showed that approximately 90% of the cisplatin in the core is
      present as the dichloro species. The remaining 10% was accounted for by a newly
      discovered dinuclear Pt compound that was identified as the positively charged
      chloride-bridged dimer of cisplatin. NMR techniques sensitive to lipid
      organization, 31P NMR and 2H NMR, revealed that the cisplatin core is coated by
      phospholipids in a bilayer configuration and that the interaction between solid
      core and bilayer coat exerts a strong ordering effect on the phospholipid
      molecules. Compared to phospholipids in liposomal membranes, the motion of the
      phospholipid headgroups is restricted and the ordering of the acyl chains is
      increased, particularly in PS. The implications of these findings for the
      structural organization, the mechanism of formation, and the mode of action of
      cisplatin nanocapsules are discussed.

PMID- 15493942
TI  - Chirality control in optically active polysilane aggregates.
AB  - A novel strategy for controlling the higher order chirality of aggregates
      prepared from enantiopure polysilanes is experimentally probed and discussed.
      Structurally similar poly[n-alkyl(aryl)]silanes were synthesized in which one
      side chain comprised the chiral (S)-2-methylbutyl group and the other an achiral
      m- or p-alkyl-substituted phenyl ring. In solution the polymers adopt helical
      conformations with the same induced preferential screw sense chirality, as
      evidenced by circular dichroism (CD) spectroscopy. Aggregates, however, formed by
      addition of a nonsolvent to a polymer solution, show oppositely signed CD
      spectra. Consistent results were obtained for another series of poly[p-n
      alkyl(aryl)]silanes where alkyl is butyl, propyl, and ethyl. The sense of the
      aggregate higher order chirality is dependent on the chemical composition and
      environment and is coarse-tunable by adjusting the length of the achiral side
      chain and fine-tunable by adjusting the good/poor solvent ratio. The origin of
      these effects is discussed with reference to a simple model.

PMID- 15493943
TI  - Optical properties of silicon clusters in the presence of water: a first
      principles theoretical analysis.
AB  - We investigate the impact of water on the optical absorption of prototypical
      silicon clusters. Our clusters contain 5 silicon atoms, tetrahedrally coordinated
      and passivated with either hydrogen or oxygen. We approach this complex problem
      by assessing the contributions of three factors: chemical reactivity, thermal
      equilibration, and dielectric screening. We find that the silanone (Si=O)
      functional group is not chemically stable in the presence of water and exclude
      this as a source of significant red shift in absorption in aqueous environments.
      We perform first principles molecular dynamics simulations of the solvation of a
      chemically stable, oxygenated silicon cluster with explicit water molecules at
      300 K. We find a systematic 0.7 eV red shift in the absorption gap of this
      cluster, which we attribute to thermally induced fluctuations in the molecular
      structure. Surprisingly, we find no observable screening impact of the solvent,
      in contrast with consistent blue shifts observed for similarly sized organic
      molecules in polar solvents. The predicted red shift is expected to be
      significantly smaller for larger Si quantum dots produced experimentally,
      guaranteeing that their vacuum optical properties are preserved even in aqueous
      environments.

PMID- 15493944
TI  - Single-molecule spectroscopy studies of microenvironmental acidity in silicate
      thin films.
AB  - Single-molecule (SM) spectroscopic methods were employed to study single site
      variations in the acidity properties of sol-gel-derived silicate films. The pH
      sensitive dye Carboxy SNARF-1 (C.SNARF-1) was used to sense film acidity. Its
      concentration in the films was maintained at nanomolar levels to allow for SMs to
      be spectroscopically interrogated. The ratio of C.SNARF-1 fluorescence at 580 nm
      (protonated form) and 640 nm (deprotonated form) was used to characterize local
      film pH. SM data were acquired both for "untreated" films and for those treated
      by immersion for either 1 or 8 h in phosphate solutions of different pH. The SM
      results prove that the spectral variability observed is dominated by static
      variations in the local matrix acidity. Shorter immersion times lead to
      relatively broad histograms and broad "titration" curves, providing clear
      evidence for kinetic limitations to access of certain film environments by the
      immersion solutions. Films subjected to longer immersion times generally exhibit
      narrower histograms. Particularly narrow distributions were obtained for films
      treated near pH 8-9, while much broader histograms were produced near pH 7. These
      results are attributed to the buffering effects of surface silanols near pH 9 and
      enhanced pH sensitivity of the dye near pH 7.

PMID- 15493945
TI  - Endohedral silicon fullerenes sinN (27 < or = N < or = 39).
AB  - We have performed an unbiased search for the lowest-energy geometric structures
      of medium-sized silicon clusters SiN (27 < or = N < or = 39) using a genetic
      algorithm and nonorthogonal-tight-binding method, followed by a refining and
      biased search using basin-hopping method coupled with density-functional theory.
      We show that the carbon fullerene cages are most likely generic cage motifs
      ("magic cages") to form low-lying stuffed-cage silicon clusters (beyond the size
      N > 27). An empirical rule that provides optimal "stuffing/cage" combinations for
      constructing low-energy endohedral silicon fullerenes is suggested, with a hope
      that it can provide guidance to future synthesis of "bucky" silicon.

PMID- 15493946
TI  - Intermolecular pi-to-pi bonding between stacked aromatic dyads. Experimental and
      theoretical binding energies and near-IR optical transitions for phenalenyl
      radical/radical versus radical/cation dimerizations.
AB  - The high symmetry and stability of phenalenyl systems, both as the planar pi
      radical (P*) and as the pi-cation (P+), are desirable characteristics of
      prototypical aromatic donor/acceptor pairs that encourage their use as (binary)
      models for the study of intermolecular interactions extant in stacked molecular
      arrays. Thus, quantitative ESR spectroscopy of the paramagnetic P* identifies its
      spontaneous self-association to the diamagnetic P2, previously characterized as
      the stacked pi-dimer by X-ray crystallography. Likewise, the rapid cross
      association of P* with the closed-shell P+ leads to the stacked pi-dimer cation
      P2*+ with the "doubled" ESR spectrum diagnostic of complete (odd) electron
      delocalization. These pi-associations are confirmed by UV-vis studies that reveal
      diagnostic near-IR bands of both P2 and P2*+-strongly reminiscent of
      intermolecular charge-transfer absorptions in related aromatic (donor/acceptor)
      pi-associations. Ab initio molecular-orbital calculations for the pi-dimer P2
      predict a binding energy of DeltaED = -11 kcal mol(-1), which is in accord with
      the experimental enthalpy change of DeltaHD = -9.5 kcal mol(-1) in
      dichloromethane solution. Most importantly, the calculations reproduce the
      intermonomer spacings and reveal the delicate interplay of attractive covalent
      and dispersion forces, balanced against the repulsions between filled orbitals.
      For comparison, the binding energy in the structurally related cationic pi-pimer
      P2*+ is calculated to be significantly larger with DeltaEP approximately -20 kcal
      mol(-1) (gas phase), owing to favorable electrostatic interactions not present in
      the neutral pi-dimer (which outweigh the partial loss of covalent interactions).
      As a result, our theoretical formulation can correctly account for the
      experimental enthalpy change in solution of DeltaHP = -6.5 kcal mol(-1) by the
      inclusion of differential ionic solvation in the formation of the pi-pimer.

PMID- 15493947
TI  - Building blocks for n-type molecular and polymeric electronics. Perfluoroalkyl-
      versus alkyl-functionalized oligothiophenes (nT; n = 2-6). Systematics of thin
      film microstructure, semiconductor performance, and modeling of majority charge
      injection in field-effect transistors.
AB  - The solid-state properties and FET electrical behavior of several series of
      alpha,omega- and beta,beta'-fluorocarbon- and alkyl-substituted and unsubstituted
      oligothiophenes nTs (n = 2-6) are compared and contrasted. The thin films were
      grown by slow vacuum deposition over a range of substrate temperatures and/or by
      casting from solution and were investigated by X-ray diffraction and scanning
      electron microscopy. Our results indicate that vacuum deposition at 60-80 degrees
      C affords films with remarkably similar microstructures despite the extensive H -
      > F substitution. Trends in observed d spacing versus molecular core extension
      provide quantitative information on molecular orientation. Field-effect
      transistor measurements performed for all systems and having the same device
      structure, components, and fabrication conditions demonstrate that all nTs
      functionalized with fluorocarbon chains at the thiophene termini are n-type
      semiconductors, in contrast to the p-type activity of the remaining systems. One
      of these systems, alpha,omega-diperfluorohexyl-4T, exhibits a mobility of 0.22
      cm2/(V s) and an Ion:Ioff ratio of 10(6), one of the highest so far reported for
      an n-type organic semiconductor. The effect of substitution regiochemistry on FET
      majority charge carrier was additionally studied, in the case of a 6T core, by
      shifting the fluorocarbon substituents from the terminal to the central thiophene
      units. Finally, we propose a simple theoretical model for electrode/organic
      interfacial carrier injection. The results suggest why modest substituent-induced
      changes in the injection barrier can produce working n-type materials.

PMID- 15493948
TI  - Same old story? Do we need to modify our supportive care treatment of elderly
      cancer patients? Focus on antiemetics.
AB  - The incidence of cancer is highest among individuals > or =65 years of age.
      Physiological changes associated with aging, such as cognitive decline, renal and
      hepatic dysfunction, can often complicate treatment options, and the elderly
      represent a particular challenge to the oncologist because of the high incidence
      of comorbidity and polypharmacy. Effective supportive care is of particular
      importance in elderly cancer patients as they may recover less satisfactorily if
      adverse events are poorly controlled. Nevertheless, evidence suggests that
      supportive care agents, for example, antiemetics, are underutilised in this
      patient population. Chemotherapy and radiotherapy regimens are frequently
      associated with nausea and vomiting--symptoms that can have deleterious effects
      on vulnerable patients if not adequately managed. The serotonin 5-HT3-receptor
      antagonists represent a class of antiemetics that are currently regarded as the
      gold standard treatment for chemotherapy- and radiotherapy-induced nausea and
      vomiting. They are recommended as first-line treatment for patients at moderate
      to-high risk of emesis. However, antiemetic guidelines do not differentiate
      between these agents and, more importantly, do not contain specific
      recommendations for the elderly. Pharmacological differences exist between the
      commonly available 5-HT3-receptor antagonists (dolasetron, granisetron,
      ondansetron, tropisetron and palonosetron), namely receptor sensitivity, duration
      of action, metabolism and tolerability profile. Of particular concern with
      prescriptions to elderly cancer patients is the convenience of once-daily
      administration, the low potential for drug-drug interactions and cardiovascular
      adverse effect profile. Moreover, the addition of the newly approved neurokinin
      NK1-receptor antagonist aprepitant to the choice of antiemetic regimen may
      complicate therapy and exacerbate the drug-drug interaction risk in elderly
      patients. Therefore, the use of antiemetics that are well tolerated and with the
      lowest risk of drug-drug interactions is imperative in this patient population
      and will enable even those patients with several comorbidities and a high level
      of polypharmacy to receive effective antiemetic therapy.

PMID- 15493949
TI  - Optimal treatment of infected diabetic foot ulcers.
AB  - Foot ulceration can lead to devastating consequences in diabetic patients. They
      are not only associated with increased morbidity but also mortality. Foot
      infections result as a consequence of foot ulceration, which can occasionally
      lead to deep tissue infections and osteomyelitis; both of which can result in
      loss of limb. To prevent amputations prompt diagnosis and treatment is required.
      Understanding the pathology of the diabetic foot will help in the planning of
      appropriate investigations and treatment. Clinical diagnosis of infection is
      based on the presence of discharge from the ulcer, cellulitis, warmth and signs
      of toxicity; though the latter is uncommon. Deep tissue samples from the ulcer
      and/or blood cultures should be taken before, but without delaying the start of
      antibacterial treatment in limb and life-threatening infections. In milder
      infections wound sampling may direct appropriate antibacterial treatment.
      Staphylococcus aureus, followed by streptococci are the most common organisms
      causing infection and antibacterial treatment should be targeted against these
      organisms in mild infection possibly with monotherapy. But in serious infections
      combination therapy is required because these are usually caused by multiple
      organisms including anaerobes. Drug-resistant organisms are becoming more
      prevalent and methicillin-resistant infections can be treated effectively with a
      number of oral antibacterials either as monotherapy or in combination. Surgical
      treatment with debridement, for example, callus removal or drainage of pus form
      an important part of diabetic foot ulcer management especially in the presence of
      infection. Occasionally limited surgery including dead infected bone removal may
      be necessary for resolution of infection. Amputation is sometimes required as a
      last resort for limb or life preservation.

PMID- 15493950
TI  - Drug treatment of pneumococcal pneumonia in the elderly.
AB  - Streptococcus pneumoniae has been recognised as a major cause of pneumonia since
      the time of Sir William Osler. Drug-resistant S. pneumoniae (DRSP), which have
      gradually become resistant to penicillins as well as more recently developed
      macrolides and fluoroquinolones, have emerged as a consequence of indiscriminate
      use of antibacterials coupled with the ability of the pneumococcus to adapt to a
      changing antibacterial milieu. Pneumococci use cell wall choline components to
      bind platelet-activating factor receptors, colonise mucosal surfaces and evade
      innate immune defenses. Numerous virulence factors that include hyaluronidase,
      neuraminidase, iron-binding proteins, pneumolysin and autolysin then facilitate
      cytolysis of host cells and allow tissue invasion and bloodstream dissemination.
      Changes in pneumococcal cell wall penicillin-binding proteins account for
      resistance to penicillins, mutations in the ermB gene cause high-level macrolide
      resistance and mutations in topoisomerase IV genes coupled with GyrA gene
      mutations alter DNA gyrase and lead to high-level fluoroquinolone resistance.
      Risk factors for lower respiratory tract infections in the elderly include age
      associated changes in oral clearance, mucociliary clearance and immune function.
      Other risks for developing pneumonia include poor nutrition, hypoalbuminaemia,
      bedridden status, aspiration, recent viral infection, the presence of chronic
      organ dysfunction syndromes including parenchymal lung disease and recent
      antibacterial therapy. Although the incidence of infections caused by DRSP is
      rising, the effect of an increase in the prevalence of resistant pneumococci on
      mortality is not clear. When respiratory infections occur, rapid diagnosis and
      prompt, empirical administration of appropriate antibacterial therapy that
      ensures adequate coverage of DRSP is likely to increase the probability of a
      successful outcome when treating community-acquired pneumonia in elderly
      patients, particularly those with multiple risk factors for DRSP. A chest x-ray
      is recommended for all patients, but other testing such as obtaining a sputum
      Gram's smear is not necessary and should not prolong the time gap between
      clinical suspicion of pneumonia and antibacterial administration. The selection
      of antibacterials should be based upon local resistance patterns of suspected
      organisms and the bactericidal efficacy of the chosen drugs. If time-dependent
      agents are chosen and DRSP are possible pathogens, dosing should keep drug
      concentrations above the minimal inhibitory concentration that is effective for
      DRSP. Treatment guidelines and recent studies suggest that combination therapy
      with a beta-lactam and macrolide may be associated with a better outcome in
      hospitalised patients, and overuse of fluoroquinolones as a single agent may
      promote quinolone resistance. The ketolides represent a new class of macrolide
      like antibacterials that are highly effective in vitro against macrolide- and
      azalide-resistant pneumococci. Pneumococcal vaccination with the currently
      available polysaccharide vaccine is thought to confer some preventive benefit
      (preventing invasive pneumococcal disease), but more effective vaccines, such as
      nonconjugate protein vaccines, need to be developed that provide broad protection
      against pneumococcal infection.

PMID- 15493952
TI  - Darifenacin: in the treatment of overactive bladder.
AB  - Darifenacin is a selective muscarinic M3-receptor antagonist that has been
      evaluated in clinical trials in patients with overactive bladder syndrome (OAB)
      using a controlled-release formulation. In multicentre, randomised, double-blind
      trials in patients with OAB, darifenacin 7.5 or 15 mg once daily for 12 weeks
      significantly reduced the frequency of urinary incontinence, frequency of
      micturition and frequency and severity of urgency versus placebo. A significant
      difference from placebo was apparent 2 weeks after starting treatment. At a
      dosage of 30 mg once daily, darifenacin significantly prolonged warning time
      compared with placebo. Darifenacin 15 mg once daily for 2 weeks was as effective
      as oxybutynin 5 mg three times daily at reducing the frequency of urinary
      incontinence and frequency and severity of urgency in patients with OAB.
      Darifenacin was generally well tolerated in clinical trials. The most common
      adverse events were dry mouth and constipation. CNS tolerability appeared to be
      similar to that of placebo. Darifenacin had no adverse effect on cognitive
      function in healthy elderly volunteers.

PMID- 15493951
TI  - New progestogens: a review of their effects in perimenopausal and postmenopausal
      women.
AB  - The progestins have different pharmacological properties depending upon the
      parent molecule, usually testosterone or progesterone, from which they are
      derived. Very small structural changes in the parent molecule may induce
      considerable differences in the activity of the derivative. In postmenopausal
      women with an intact uterus, progestins are used in combination with estrogen as
      hormone-replacement therapy (HRT). The development of new generations of
      progestins with improved selectivity profiles has been a great challenge.
      Steroidal and nonsteroidal progesterone-receptor (PR) agonists have been
      synthesised as well, although the latter are still in a very early stage of
      development. Several new progestins, which have been synthesised in the last 2
      decades, may be considered fourth-generation progestins. These include dienogest,
      drospirenone, Nestorone (Population Council, New York, NY, USA), nomegestrol
      acetate and trimegestone. The fourth-generation progestins have been designed to
      have no androgenic or estrogenic actions and to be closer in activity to the
      physiological hormone progesterone. Drospirenone differs from the classic
      progestins as it is derived from spirolactone. It is essentially an
      antimineralocorticoid steroid with no androgenic effect but a partial
      antiandrogenic effect. The antiovulatory potency of the different progestins
      varies. Trimegestone and Nestorone are the most potent progestins synthesised to
      date, followed by two of the older progestins, 3-keto-desogestrel and
      levonorgestrel. The new molecules trimegestone, drospirenone and dienogest also
      have antiandrogenic activity. Following the publication of the results of the
      Women's Health Initiative study, the role of progestins in HRT became
      controversial. Unfortunately, this concern has been directed towards progestins
      as a class, although striking differences exist among the progestins. Natural
      progesterone and some of its derivatives, such as the 19-norprogesterone
      molecules, and the new molecules drospirenone and dienogest are not androgenic
      and, therefore, have no negative effect on the lipid profile. The effects of
      progestins on breast tissue remain controversial as well. However, depending on
      the progestin and the duration of application, breast cell differentiation and
      apoptosis may predominate over proliferation. It is still unclear if the
      currently available progestins are able to bind specifically to the PR isoforms
      PR-A or PR-B and whether this is of clinical relevance to breast cell
      proliferation is also unclear. Although it is likely that the new progestins may
      have neutral effects on the risk of coronary heart disease or breast cancer in
      younger postmenopausal women, this hypothesis must be confirmed in large
      randomised, well controlled clinical trials.

PMID- 15493956
TI  - Antioxidant defenses and DNA damage induced by UV-A and UV-B radiation in the
      crab Chasmagnathus granulata (Decapoda, Brachyura).
AB  - The photoprotector role of pigment dispersion in the melanophores of the crab,
      Chasmagnathus granulata, against DNA and oxidative damages caused by UV-A and UV
      B was investigated. Intact and eyestalkless crabs were used. In eyestalkless
      crabs, the dorsal epidermis of the cephalothorax (dispersed melanophores) and the
      epidermis of pereiopods (aggregated melanophores) were analyzed. Intact crabs
      showed only dispersed melanophores in the two epidermis. Antioxidant enzymes
      activity and lipoperoxidation content were analyzed after UV-A (2.5 J/cm2) or UV
      B (8.6 J/cm2) irradiation. DNA damage was analyzed by single cell electrophoresis
      (comet) assay, after exposure to UV-B (8.6 J/cm2). UV-A radiation increased the
      glutatione-S-transferase activity in the pereiopods epidermis of eyestalkless
      crabs (P<0.05). UV-B radiation induced DNA damage in the dorsal epidermis of
      eyestalkless crabs (P<0.05). In pereiopod epidermis of eyestalkless crabs, there
      was no significant difference between control and UV-B-exposed crabs. In the
      pereiopods epidermis of eyestalkless, the control group showed higher scores of
      DNA damage and approximately 50% of cellular viability. Because in eyestalkless
      and irradiated crabs the cellular viability was approximately 5%, it was not
      possible to observe nuclei for determination of DNA damage. The findings show
      that melanophores can play a role in the defense against harmful effects of a
      momentary exposure to UV radiation.

PMID- 15493957
TI  - The photochemistry of thymidylyl-(3'-5')-5-methyl-2'-deoxycytidine in aqueous
      solution.
AB  - The photochemistry of the dinucleoside monophosphate thymidylyl-(3'-5')-5-methyl
      2'-deoxycytidine (Tpm5dC) has been studied in aqueous solution using both 254 nm
      and UV-B radiation. A variety of dinucleotide photoproducts containing 5
      methylcytosine (m5C) have been isolated and characterized. These include two
      cyclobutane dimers (CBD) (the cis-syn [c,s]and trans-syn forms), a (6-4) adduct
      and its related Dewar isomer, and two isomers of a product in which the m5C
      moiety was converted into an acrylamidine. Small amounts of thymidylyl-(3'-5')
      thymidine (TpT) were also formed, presumably as a secondary photoreaction
      product. In addition, a photoproduct was characterized in which the m5C moiety
      was lost, thus generating 3'-thymidylic acid esterified with 2'-deoxyribose at
      the 5-hydroxyl on the sugar moiety. The c,s CBD of Tpm5dC readily undergoes
      deamination to form the corresponding CBD of TpT. The kinetics of this
      deamination process has been studied; the corresponding enthalpy and entropy of
      activation for the reaction have been evaluated at pH 7.4 as being, respectively,
      73.4 kJ/mol and -103.5 J/K mol. Deamination was not observed for the other
      characterized photoproducts of Tpm5dC.

PMID- 15493958
TI  - Photochemistry of phytoalexins containing phenalenone-like chromophores:
      photophysics and singlet oxygen photosensitizing properties of the plant
      oxoaporphine alkaloid oxoglaucine.
AB  - Oxoglaucine (OG) is an oxoaporphine alkaloid, which has been linked to plant
      defense mechanisms. It contains a phenalenone (PN)-like chromophore, which
      suggests a role as singlet oxygen ((1)O(2)) photosensitizer. Indeed, OG is able
      to photosensitize (1)O(2) with 100% efficiency in nonpolar environments, similar
      to PN. However, this efficiency decreases in polar and protic media, although
      (1)O(2) is formed in all environments ranging from benzene to water. OG is a
      rather inefficient (1)O(2) quencher (k(q) = 8 x 10(5) M(-1) s(-1)) unlike the
      related alkaloids boldine and glaucine, for which an antioxidant role has been
      suggested. The results of this study contribute to the view that plant defense
      mediated by PN-like secondary metabolites may have a photochemical component.

PMID- 15493959
TI  - Photoinduced DNA cleavage and cellular damage in human dermal fibroblasts by 2,3
      diaminophenazine.
AB  - Aromatic amines, such as o-phenylenediamine (OPD), have been used extensively in
      commercial hair dyes and in the synthesis of agricultural pesticides. Air
      oxidation of OPD results in the formation of 2,3-diaminophenazine (DAP). Although
      the mutagenic toxicity of DAP has been shown in both prokaryotic and eukaryotic
      systems, its phototoxicity remains largely unexplored. This study focuses on the
      pH-dependent photophysical properties of DAP and demonstrates its ability to
      photoinduce DNA damage to pUC19 plasmid in vitro. The photocytotoxicity of DAP
      toward human skin fibroblasts was also measured. DAP exhibits weak intercalative
      binding to double-stranded DNA with a binding constant K(b) = 3.5 x 10(3) M(-1).
      Furthermore, upon irradiation with visible light, DAP is able to nick plasmid DNA
      in the presence of oxygen. The concentration of DAP that resulted in 50% cell
      death was 172 +/- 9 microM in the dark and 13 +/- 1 microM after irradiation of
      the DAP-treated cell cultures with visible light (400-700 nm, 30 min, 5 J/cm(2)).
      The 13-fold increase in toxicity upon exposure to visible light shows the need
      for further study of the photocytotoxicity of contaminants such as DAP.

PMID- 15493960
TI  - Pomegranate fruit extract modulates UV-B-mediated phosphorylation of mitogen
      activated protein kinases and activation of nuclear factor kappa B in normal
      human epidermal keratinocytes paragraph sign.
AB  - Excessive exposure of solar ultraviolet (UV) radiation, particularly its UV-B
      component, to humans causes many adverse effects that include erythema,
      hyperplasia, hyperpigmentation, immunosuppression, photoaging and skin cancer. In
      recent years, there is increasing use of botanical agents in skin care products.
      Pomegranate derived from the tree Punica granatum contains anthocyanins (such as
      delphinidin, cyanidin and pelargonidin) and hydrolyzable tannins (such as
      punicalin, pedunculagin, punicalagin, gallagic and ellagic acid esters of
      glucose) and possesses strong antioxidant and anti-inflammatory properties.
      Recently, we have shown that pomegranate fruit extract (PFE) possesses antitumor
      promoting effects in a mouse model of chemical carcinogenesis. To begin to
      establish the effect of PFE for humans in this study, we determined its effect on
      UV-B-induced adverse effects in normal human epidermal keratinocytes (NHEK). We
      first assessed the effect of PFE on UV-B-mediated phosphorylation of mitogen
      activated protein kinases (MAPK) pathway in NHEK. Immunoblot analysis
      demonstrated that the treatment of NHEK with PFE (10-40 microg/mL) for 24 h
      before UV-B (40 mJ/cm(2)) exposure dose dependently inhibited UV-B-mediated
      phosphorylation of ERKl/2, JNK1/2 and p38 protein. We also observed that PFE (20
      microg/mL) inhibited UV-B-mediated phosphorylation of MAPK in a time-dependent
      manner. Furthermore, in dose- and time-dependent studies, we evaluated the effect
      of PFE on UV-B-mediated activation of nuclear factor kappa B (NF-kappaB) pathway.
      Using Western blot analysis, we found that PFE treatment of NHEK resulted in a
      dose- and time-dependent inhibition of UV-B-mediated degradation and
      phosphorylation of IkappaBalpha and activation of IKKalpha. Using immunoblot
      analysis, enzyme-linked immunosorbent assay and electrophoretic mobility shift
      assay, we found that PFE treatment to NHEK resulted in a dose- and time-dependent
      inhibition of UV-B-mediated nuclear translocation and phosphorylation of NF
      kappaB/p65 at Ser(536). Taken together, our data shows that PFE protects against
      the adverse effects of UV-B radiation by inhibiting UV-B-induced modulations of
      NF-kappaB and MAPK pathways and provides a molecular basis for the
      photochemopreventive effects of PFE.

PMID- 15493961
TI  - Perception of color and material properties in complex scenes.
AB  - How do human observers estimate the location, form, and color of objects?
      Accurate estimation is challenging because the light arriving at the eyes depends
      not only on object properties, but also on the spectra and spatial layout of the
      light sources (Nassau, 1983; Foley et al., 1990). How well the visual system
      separates illuminant and object properties to achieve a stable representation has
      traditionally been studied under the rubric of color and lightness constancy.
      Most previous work used very simple stimuli, typically a few diffusely
      illuminated surfaces arranged perpendicular to the line of sight. Over the past
      several years, however, there has been an evident increase of interest in
      expanding the conceptualization of this area to incorporate effects that emerge
      only for complex, typically three-dimensional, scenes. The current issue features
      papers that represent various manifestations of this interest. One line of
      research investigates how the three-dimensional layout of a scene affects the
      perception of lightness and color. Although the current work has long-standing
      antecedents (e.g. Mach, 1886/1959; Hochberg and Beck, 1954; Gilchrist, 1980),
      methodological advances in i) experimentation with real illuminated objects (e.g.
      Brainard et. al, 1987; Rutherford and Brainard, 2002; Ripamonti et al., 2004;
      Robilotto and Zaidi, 2004), ii) the use of sophisticated graphics simulations
      (e.g. Yang and Maloney, 1999; Fleming, Dror, & Adelson, 2003; Boyaci, Maloney, &
      Hersh, 2003; Delahunt and Brainard, 2004), iii) the design of hybrid systems that
      combine real objects with image-based graphics and video projection (Ling and
      Hurlbert, 2004), and iv) psychophysical procedures (Maloney and Yang, 2003;
      Obein, Knoblauch, & Vienot, 2004) have opened the door for systematic exploration
      of a wider range of phenomena. Recent papers include work on how well vision
      compensates for changes in surface orientation (Boyaci et al., 2003; Ripamonti et
      al., 2004), how effectively it discounts inter-reflections among nearby surfaces
      (Bloj, Kersten, & Hurlbert, 1999; Doerschner, Boyaci, & Maloney, 2004; Delahunt
      and Brainard, 2004), and how the visual system effectively estimates the spectral
      properties and spatial layout of the illuminant in three-dimensional scenes
      (Kraft & Brainard, 1999; Yang & Maloney, 1999; Boyaci, Maloney, & Hersh, 2003;
      Bloj et al., 2004; Boyaci, Doerschner, & Maloney, 2004; Khang and Zaidi, 2004).
      The second thread that leads to papers in the current issue is a focus on the
      functional utility of color and lightness perception -- the idea that these
      percepts inform us about the properties of objects rather than those of light
      spectra. This focus resulted in a renaissance of research in color constancy over
      the past two decades, with particular progress being made in the development of
      computational models that explore how, in principle, object surface properties
      can be estimated from image data. As with the experimental lines, early work
      focused on simple scene geometries (for reviews see Hurlbert, 1998; Maloney,
      1999) but consideration has recently expanded to three-dimensional configurations
      (Adelson and Pentland, 1996; Yang and Maloney, 1999; Bell and Freeman, 2001;
      Dror, Willsky, & Adelson, 2004) Of particular interest has been the elaboration
      of purely computational formulations into parametric models of human performance
      (e.g. Brainard Brunt, & Speigle, 1997; Brainard Kraft, & Longere, 2003; Boyaci et
      al., 2003; Doerschner et al., 2004; Boyaci et al., 2004; Bloj et al., 2004),
      tests of how well the visual system exploits image information identified in
      computational studies (Yang and Maloney, 2001; Delahunt and Brainard, 2004;
      Smithson and Zaidi, 2004), investigations of how well the visual system recovers
      perceptual correlates of material properties other than diffuse surface
      reflectance, such as gloss and translucency (Lu, Koenderink, & Kappers, 2000;
      Fleming et al., 2003; Pont & Koenderink, 2003; Obein et al., 2004), as well as
      how geometric aspects of surface reflectance interact with the perception of
      shape (Fleming et al., 2003).

PMID- 15493962
TI  - Perceived surface color in binocularly viewed scenes with two light sources
      differing in chromaticity.
AB  - We examined the effect of perceived orientation on the perceived color of matte
      surfaces in rendered three-dimensional scenes illuminated by a blue diffuse light
      and a yellow punctate light. On each trial, observers first adjusted the color of
      a matte test patch, placed near the center of the scene, until it appeared
      achromatic, and then estimated its orientation by adjusting a monocular gradient
      probe. The orientation of the test patch was varied from trial to trial by the
      experimental program, effectively varying the chromaticity of the light mixture
      from the two light sources that would be absorbed and reemitted by a neutral test
      patch. We found that observers' achromatic settings varied with perceived
      orientation but that observers only partially discounted orientation in making
      achromatic settings. We developed an equivalent illuminant model for our task in
      which we assumed that observers discount orientation using possibly erroneous
      estimates of the chromaticities of the light sources and/or their spatial
      distribution. We found that the observers' failures could be explained by two
      factors: errors in estimating the direction to the punctate light source and
      errors in estimating the chromaticities of the two light sources. We discuss the
      pattern of errors in estimating these factors across observers.

PMID- 15493963
TI  - Illuminant color perception of spectrally filtered spotlights.
AB  - The color perceived to belong to the illumination of objects is often based on
      cues from the scene within which the objects are perceived, instead of being
      based on any view of the source itself. We present measurements of illuminant
      color estimation by human observers for moving, spectrally filtered spotlights.
      The results show that when only one illuminant is in the field of view, estimates
      of illuminant color are seriously biased by the chromaticities of the illuminated
      surfaces. When the surround of the spotlight is illuminated by a dimmer second
      light, spotlight matching moves toward veridical in most conditions. Simulations
      show that a gray-world model cannot be rejected as an adequate explanation for
      illuminant color estimation and provides as good a fit as a model that gives
      greater weights to the brightest surfaces. When the surrounding illuminant is
      brighter than the spotlight, the situation is similar to that of a moving filter.
      Spotlight matches are close to veridical, and the results can be fit by a model
      based on estimating both illuminants.

PMID- 15493964
TI  - Colour constancy in context: roles for local adaptation and levels of reference.
AB  - By determining the locations of boundaries between colour categories, we measured
      changes in the colour appearance of test-reflectances as a function of the
      simulated illumination. Test-reflectances were displayed against a variegated
      background of reflectance samples. Under prolonged adaptation to each illuminant,
      observers demonstrated a high degree of appearance-based colour constancy. By
      using backgrounds that consisted of chromatically biased sets of reflectances, we
      tested whether this stability depends on estimates of the illuminant's cone
      coordinates based on simple scene statistics. The chromatic bias of the
      background had only a small effect on the classification of test materials. To
      compare the roles of spatially local and spatially extended estimation processes,
      we then (unknown to the observer) simulated different illuminants on the test and
      on the background. Observers continued to demonstrate reasonable colour
      constancy. To examine the relative roles of automatic adaptation and perceptual
      strategies, we reduced the duration of exposure to the test compared to exposure
      to the background (under the conflicting illuminant). The results suggest that
      mechanisms that preserve information across successive test-presentations (e.g.
      spatially local adaptation with a time course of a few seconds, and perceptual
      adjustments to levels of reference) are key determinants of the stability of
      colour appearance.

PMID- 15493965
TI  - Difference scaling of gloss: nonlinearity, binocularity, and constancy.
AB  - Gloss is an attribute of visual appearance that originates from the geometrical
      distribution of the light reflected by the surface. We used the maximum
      likelihood difference scaling (MLDS) procedure (L.T. Maloney & J. N. Yang, 2003)
      to estimate gloss scales over an extended range. Observers' judgments were
      obtained for a series of 10 black, coated samples for two directions of
      illumination, in binocular and monocular vision. The results showed a nonlinear
      relation between gloss percept and instrumental specular gloss values.
      Sensitivity is higher at extreme scale values than in the middle. In binocular
      vision, the sensitivity to gloss is higher than in monocular vision exclusively
      for high gloss levels. Lastly, we found that gloss difference scales, when
      expressed in terms of the samples rather than the photometric characteristics,
      vary little with the direction of illumination. Gloss scaling thus seems to be
      independent of the geometrical variations of the luminous flux at the surface of
      the sample. By analogy with the term "color constancy," we call this property
      "gloss constancy."

PMID- 15493966
TI  - Color and size interactions in a real 3D object similarity task.
AB  - In the natural world, objects are characterized by a variety of attributes,
      including color and shape. The contributions of these two attributes to object
      recognition are typically studied independently of each other, yet they are
      likely to interact in natural tasks. Here we examine whether color and size (a
      component of shape) interact in a real three-dimensional (3D) object similarity
      task, using solid domelike objects whose distinct apparent surface colors are
      independently controlled via spatially restricted illumination from a data
      projector hidden to the observer. The novel experimental setup preserves natural
      cues to 3D shape from shading, binocular disparity, motion parallax, and surface
      texture cues, while also providing the flexibility and ease of computer control.
      Observers performed three distinct tasks: two unimodal discrimination tasks, and
      an object similarity task. Depending on the task, the observer was instructed to
      select the indicated alternative object which was "bigger than," "the same color
      as," or "most similar to" the designated reference object, all of which varied in
      both size and color between trials. For both unimodal discrimination tasks,
      discrimination thresholds for the tested attribute (e.g., color) were increased
      by differences in the secondary attribute (e.g., size), although this effect was
      more robust in the color task. For the unimodal size-discrimination task, the
      strongest effects of the secondary attribute (color) occurred as a perceptual
      bias, which we call the "saturation-size effect": Objects with more saturated
      colors appear larger than objects with less saturated colors. In the object
      similarity task, discrimination thresholds for color or size differences were
      significantly larger than in the unimodal discrimination tasks. We conclude that
      color and size interact in determining object similarity, and are effectively
      analyzed on a coarser scale, due to noise in the similarity estimates of the
      individual attributes, inter-attribute attentional interactions, or coarser
      coding of attributes at a "higher" level of object representation.

PMID- 15493967
TI  - An equivalent illuminant model for the effect of surface slant on perceived
      lightness.
AB  - In the companion study (C. Ripamonti et al., 2004), we present data that measure
      the effect of surface slant on perceived lightness. Observers are neither
      perfectly lightness constant nor luminance matchers, and there is considerable
      individual variation in performance. This work develops a parametric model that
      accounts for how each observer's lightness matches vary as a function of surface
      slant. The model is derived from consideration of an inverse optics calculation
      that could achieve constancy. The inverse optics calculation begins with
      parameters that describe the illumination geometry. If these parameters match
      those of the physical scene, the calculation achieves constancy. Deviations in
      the model's parameters from those of the scene predict deviations from constancy.
      We used numerical search to fit the model to each observer's data. The model
      accounts for the diverse range of results seen in the experimental data in a
      unified manner, and examination of its parameters allows interpretation of the
      data that goes beyond what is possible with the raw data alone.

PMID- 15493968
TI  - Measurements of the effect of surface slant on perceived lightness.
AB  - When a planar object is rotated with respect to a directional light source, the
      reflected luminance changes. If surface lightness is to be a reliable guide to
      surface identity, observers must compensate for such changes. To the extent they
      do, observers are said to be lightness constant. We report data from a lightness
      matching task that assesses lightness constancy with respect to changes in object
      slant. On each trial, observers viewed an achromatic standard object and
      indicated the best match from a palette of 36 grayscale samples. The standard
      object and the palette were visible simultaneously within an experimental
      chamber. The chamber illumination was provided from above by a theater stage
      lamp. The standard objects were uniformly-painted flat cards. Different groups of
      naive observers made matches under two sets of instructions. In the Neutral
      Instructions, observers were asked to match the appearance of the standard and
      palette sample. In the Paint Instructions, observers were asked to choose the
      palette sample that was painted the same as the standard. Several broad
      conclusions may be drawn from the results. First, data for most observers were
      neither luminance matches nor lightness constant matches. Second, there were
      large and reliable individual differences. To characterize these, a constancy
      index was obtained for each observer by comparing how well the data were
      accounted for by both luminance matching and lightness constancy. The index could
      take on values between 0 (luminance matching) and 1 (lightness constancy).
      Individual observer indices ranged between 0.17 and 0.63 with mean 0.40 and
      median 0.40. An auxiliary slant-matching experiment rules out variation in
      perceived slant as the source of the individual variability. Third, the effect of
      instructions was small compared to the inter-observer variability. Implications
      of the data for models of lightness perception are discussed.

PMID- 15493969
TI  - Color constancy under changes in reflected illumination.
AB  - Distinct physical processes can change the spectrum of the illumination that
      impinges on a surface. Here we consider two such changes. The first is a change
      in the spectrum of the light source that provides the scene illumination (light
      source change). The second is a change in the reflectance of a surface located
      near a test surface of interest (reflected light change). A color constant visual
      system must compensate for changes caused by both of these physical processes. We
      report measurements of constancy with respect to reflected light changes and
      compare them to results from a recent experiment that examines constancy across
      light source changes. Observers viewed synthetic images rendered from three
      dimensional scene descriptions and displayed on a CRT-based stereoscope. They
      made achromatic adjustments to test surfaces embedded in the images. The degree
      of constancy varied with the color direction of the illuminant change, and the
      variation was similar for reflected light and light source changes. The overall
      level of constancy was lower for reflected light changes than for light source
      changes. A second experiment suggests that for our conditions, constancy across
      reflected light changes is driven almost entirely by changes in the local
      surround of the test. In a third experiment, observers made asymmetric matches
      across both types of illuminant change. Here the matches were essentially
      identical across both types of illuminant change.

PMID- 15493970
TI  - Limits of lightness identification for real objects under natural viewing
      conditions.
AB  - We examined whether observers veridically perceive the reflectances of real
      objects under natural viewing conditions. A new forced-choice paradigm was used
      to measure observers' abilities to identify (not match) the reflectance of
      randomly crumpled gray papers across two levels of illumination, and also to
      simultaneously measure brightness discrimination thresholds for the same objects.
      Accuracy of lightness identification differed qualitatively among observers. By
      explicitly manipulating observer strategies, we show that when observers use
      brightness dissimilarity, their performance is similar to lightness
      identification. A brightness adaptation model simulates how instead of extracting
      lightness, observers can rely on perceived relative brightness to achieve the
      measured degrees of lightness identification.

PMID- 15493971
TI  - Specular reflections and the perception of shape.
AB  - Many materials, including leaves, water, plastic, and chrome exhibit specular
      reflections. It seems reasonable that the visual system can somehow exploit
      specular reflections to recover three-dimensional (3D) shape. Previous studies
      (e.g., J. T. Todd & E. Mingolla, 1983; J. F. Norman, J. T. Todd, & G. A. Orban,
      2004) have shown that specular reflections aid shape estimation, but the relevant
      image information has not yet been isolated. Here we explain how specular
      reflections can provide reliable and accurate constraints on 3D shape. We argue
      that the visual system can treat specularities somewhat like textures, by using
      the systematic patterns of distortion across the image of a specular surface to
      recover 3D shape. However, there is a crucial difference between textures and
      specularities: In the case of textures, the image compressions depend on the
      first derivative of the surface depth (i.e., surface orientation), whereas in the
      case of specularities, the image compressions depend on the second derivative
      (i.e., surfaces curvatures). We suggest that this difference provides a cue that
      can help the visual system distinguish between textures and specularities, even
      when present simultaneously. More importantly, we show that the dependency of
      specular distortions on the second derivative of the surface leads to distinctive
      fields of image orientation as the reflected world is warped across the surface.
      We find that these "orientation fields" are (i) diagnostic of 3D shape, (ii)
      remain surprisingly stable when the world reflected in the surface is changed,
      and (iii) can be extracted from the image by populations of simple oriented
      filters. Thus the use of specular reflections for 3D shape perception is both
      easier and more reliable than previous computational work would suggest.

PMID- 15493972
TI  - Statistical characterization of real-world illumination.
AB  - Although studies of vision and graphics often assume simple illumination models,
      real-world illumination is highly complex, with reflected light incident on a
      surface from almost every direction. One can capture the illumination from every
      direction at one point photographically using a spherical illumination map. This
      work illustrates, through analysis of photographically acquired, high dynamic
      range illumination maps, that real-world illumination possesses a high degree of
      statistical regularity. The marginal and joint wavelet coefficient distributions
      and harmonic spectra of illumination maps resemble those documented in the
      natural image statistics literature. However, illumination maps differ from
      typical photographs in that illumination maps are statistically nonstationary and
      may contain localized light sources that dominate their power spectra. Our work
      provides a foundation for statistical models of real-world illumination, thereby
      facilitating the understanding of human material perception, the design of robust
      computer vision systems, and the rendering of realistic computer graphics
      imagery.

PMID- 15493979
TI  - Chemical insights from structural studies of enzymes.
AB  - The rapid progress in structural and molecular biology over the past fifteen
      years has allowed chemists to access the structures of enzymes, of their
      complexes and of mutants. This wealth of structural information has led to a
      surge in the interest in enzymes as elegant chemical catalysts. Enzymology is a
      distinguished field and has been making vital contributions to medicine and basic
      science long before structural biology. This review for the Colworth Medal
      Lecture discusses work from the author's laboratory. This work has been carried
      out in collaboration with many other laboratories. The work has mapped out the
      chemical mechanisms and structures of interesting novel enzymes. The review tries
      to highlight the interesting chemical aspects of the mechanisms involved and how
      structural analysis has provided a detailed insight. The review focuses on
      carbohydrate-processing pathways in bacteria, and includes some recent data on an
      integral membrane protein.

PMID- 15493980
TI  - Oxidative protein folding in the mammalian endoplasmic reticulum.
AB  - Native disulphide bonds are essential for the structure and function of many
      membrane and secretory proteins. Disulphide bonds are formed, reduced and
      isomerized in the endoplasmic reticulum of mammalian cells by a family of
      oxidoreductases, which includes protein disulphide isomerase (PDI), ERp57, ERp72,
      P5 and PDIR. This review will discuss how these enzymes are maintained in either
      an oxidized redox state that allows them to form disulphide bonds in substrate
      proteins or a reduced form that allows them to perform isomerization and
      reduction reactions, how these opposing pathways may co-exist within the same
      compartment and why so many oxidoreductases exist when PDI alone can perform all
      three of these functions.

PMID- 15493981
TI  - Tail-anchored protein biosynthesis at the endoplasmic reticulum: the same but
      different.
AB  - The post-translational integration of tail-anchored proteins at the endoplasmic
      reticulum represents a novel and distinct pathway for membrane protein synthesis.
      Studies of various precursors, exemplified by the synaptobrevins and cytochrome
      b5, indicate that multiple routes may facilitate their biosynthesis. There is
      clear evidence that both cytosolic factors and membrane components facilitate the
      efficient membrane insertion of at least some tail-anchored proteins. However,
      the nature of these mediators is currently unknown and their identification will
      be an essential step in defining the molecular basis of tail-anchored protein
      biogenesis.

PMID- 15493982
TI  - Catalysis of disulphide bond formation in the endoplasmic reticulum.
AB  - Disulphide bonds are critical for the maturation and stability of secretory and
      cell-surface proteins. In eukaryotic cells, disulphide bonds are introduced in
      the ER (endoplasmic reticulum), where the redox conditions are optimal to support
      their formation. Yet, the correct pairing of cysteine residues is not simple and
      often requires the assistance of redox-active proteins. The enzymes of the thiol
      disulphide oxidoreductase family catalyse oxidation, reduction and isomerization,
      and thereby play important roles for the folding of many proteins. To allow all
      three redox reactions to take place concurrently in the same compartment,
      specific protein-protein interactions regulate the function of individual
      enzymes, while a careful balance of the ER redox environment is maintained. At
      the same time, the system must be capable of responding to changes in the
      cellular conditions, caused, for instance, by oxidative stress and protein
      misfolding. This review presents recent progress in understanding how ER redox
      conditions are regulated and how protein disulphides are formed in the ER of
      mammalian cells.

PMID- 15493983
TI  - Functional ramifications of FRET-detected nascent chain folding far inside the
      membrane-bound ribosome.
AB  - During protein biosynthesis, nascent protein chains are directed along a long
      narrow tunnel that spans the large ribosomal subunit. It has recently become
      clear that this structural feature has evolved to effect regulatory control over
      aspects of protein synthesis and protein trafficking. Since this control is
      nascent chain-specific, ribosomal components that form the tunnel must be
      involved in recognizing selected nascent proteins as they pass by. The present
      study focuses on one such situation in which nascent secretory proteins and
      membrane proteins are distinguished by the ribosome-induced folding of the
      latter's hydrophobic transmembrane sequence far inside the ribosomal tunnel and
      close to the peptidyltransferase centre.

PMID- 15493984
TI  - Distribution of lipid raft markers in live cells.
AB  - GPI (glycosylphosphatidylinositol)-anchored proteins are characteristic
      components of biochemically defined lipid rafts. Rafts may be involved in T-cell
      stimulation, but it is not clear whether molecules involved in TCR (T-cell
      receptor) signalling are partitioned to T-cell synapses through raft microdomains
      or through specific protein-protein interactions. We have used FRET (fluorescence
      resonance energy transfer) analysis to study the distribution of GPI-anchored
      fluorescent proteins in the plasma membrane of live cells. Multiple criteria
      suggested that FRET between different GPI-anchored fluorescent proteins in COS-7
      or unstimulated Jurkat T-cells is generated by a random, unclustered
      distribution. Stimulation of TCR signalling in Jurkat T-cells by beads coated
      with antibodies against TCR subunits resulted in localized increases in
      fluorescence of raft markers. However, measurements of FRET and ratio imaging
      showed that there was no detectable clustering and no overall enrichment of raft
      markers in these regions.

PMID- 15493985
TI  - Can membrane nanotubes facilitate communication between immune cells?
AB  - Recent observations have revealed that intercellular connections can be formed
      through membrane nanotubes. These delicate structures could facilitate transport
      of organelles and membrane proteins between cells. The sharing of cell surface
      and cytoplasmic components between cells could be commonplace in biology, but an
      important physiological role for membrane nanotubes between immune cells is
      difficult to test with current technology.

PMID- 15493986
TI  - Clustering of death receptors in lipid rafts initiates neutrophil spontaneous
      apoptosis.
AB  - Neutrophils die by apoptosis spontaneously within 12-24 h of their release from
      the bone marrow. The mechanism regulating entry of neutrophils into apoptosis at
      the end of their life-span is currently under debate. Our data suggest that
      neutrophil apoptosis involves a novel mechanism of caspase 8 activation that is
      indirectly regulated by accumulation of reactive oxygen species. We detected
      early activation of caspase 8 upstream of caspase 3 activation, suggesting death
      receptor signalling. The CD95 DISC (death-inducing signalling complex) was
      detected in neutrophils, but blocking antibodies to death receptors did not
      inhibit apoptosis, suggesting a novel mechanism for caspase 8 activation. Death
      receptor clustering in ceramide-rich lipid rafts is thought to be an early event
      in their signalling, so we investigated the role of ceramide generated by ASM
      (acid sphingomyelinase) in neutrophil apoptosis. Ceramide was generated early in
      neutrophil apoptosis, and ASM activity was required for neutrophil apoptosis.
      Moreover, neutrophil apoptosis was significantly delayed in ASM(-/-) mice
      compared with their wild-type littermates. CD95 DISC components were present in
      lipid rafts in neutrophils, and were progressively clustered in cultured
      neutrophils. Generation of ceramide was blocked by desferrioxamine, suggesting
      that hydroxyl radicals are important for the activation of ASM. This observation
      was in line with our earlier observation of a precipitous drop in reduced
      glutathione in the aging neutrophil.

PMID- 15493987
TI  - Intraflagellar transport motors in Caenorhabditis elegans neurons.
AB  - IFT (intraflagellar transport) assembles and maintains sensory cilia on the
      dendritic endings of chemosensory neurons within the nematode Caenorhabditis
      elegans. During IFT, macromolecular protein complexes called IFT particles (which
      carry ciliary precursors) are moved from the base of the sensory cilium to its
      distal tip by anterograde IFT motors (kinesin-II and Osm-3 kinesin) and back to
      the base by retrograde IFT-dynein [Rosenbaum and Witman (2002) Nat. Rev. Mol.
      Cell Biol. 3, 813-825; Scholey (2003) Annu. Rev. Cell Dev. Biol. 19, 423-443; and
      Snell, Pan and Wang (2004) Cell 117, 693-697]. In the present study, we describe
      the protein machinery of IFT in C. elegans, which we have analysed using time
      lapse fluorescence microscopy of green fluorescent protein-fusion proteins in
      concert with ciliary mutants.

PMID- 15493988
TI  - Myosin VI: a multifunctional motor.
AB  - Myosin VI moves towards the minus end of actin filaments unlike all the other
      myosins so far studied, suggesting that it has unique properties and functions.
      Myosin VI is present in clathrin-coated pits and vesicles, in membrane ruffles
      and in the Golgi complex, indicating that it has a wide variety of functions in
      the cell. To investigate the cellular roles of myosin VI, we have identified a
      variety of myosin VI-binding partners and characterized their interactions. As an
      alternative approach, we have studied the in vitro properties of intact myosin
      VI. Previous studies assumed that myosin VI existed as a dimer but our
      biochemical characterization and electron microscopy studies reveal that myosin
      VI is a monomer. Using an optical tweezers force transducer, we showed that
      monomeric myosin VI is a non-processive motor with a large working stroke of 18
      nm. Potential roles for myosin VI in cells are discussed.

PMID- 15493989
TI  - Imaging myosin 10 in cells.
AB  - Cellular motors (kinesin, dynein and myosin) are ubiquitous. A major task in cell
      biology is to determine how they function in cells. Here we focus on myosin 10,
      an intrafilopodial motor, and show how imaging green fluorescent protein fused to
      myosin 10 or its tail domains can help us understand the function of this myosin.

PMID- 15493990
TI  - Towards bridging the gap from molecular forces to the movement of organisms.
AB  - Muscles are responsible for generating the forces required for the movement of
      multicellular organisms. Microscopically, these forces arise as a consequence of
      motor proteins (myosin) pulling and sliding along actin filaments. Current
      knowledge states that the molecular forces between actin and myosin are linear in
      nature [Huxley and Simmons (1971) Nature (London) 233, 533-538] and that the
      physiologically observed non-linearities (e.g. Hill's force-velocity
      relationship) are a consequence of non-linearities in the attachment/detachment
      ratios. However, this view has been disputed recently [Nielsen (2002) J. Theor.
      Biol. 219, 99-119], inspired by results from protein pulling experiments showing
      that proteins often have non-linear entropic force-extension profiles.
      Irrespective of the case, the present study aims at integrating such basic force
      producing properties into large-scale simulations of muscle, which may
      accommodate macroscopic properties of muscles, e.g. the catch-like effect, the
      Henneman principle and accurate twitch force and motor unit size distributions.
      As a test of the underlying principles, a model of the biceps caput breve muscle
      is presented and compared with experimental data.

PMID- 15493991
TI  - Post-transcriptional processing of cellular RNAs in herpes simplex virus-infected
      cells.
AB  - In HSV-1 (herpes simplex virus 1)-infected cells, the U(L)41 gene product carried
      with the virion has been shown to mediate the degradation of mRNA, leading to the
      shut-off of cellular protein synthesis. Analysis of the RNAs accumulating in
      cells infected with HSV-1 revealed the accumulation of RNAs encoding numerous
      cellular proteins both associated with and independent of activation of the NF
      kappaB (nuclear factor kappaB) pathway. Studies on the activation of NF-kappaB
      and the expression and fate of selected cellular transcripts revealed the
      following. (i) In HSV-1-infected cells, NF-kappaB is activated by activated
      protein kinase R. Furthermore, the blockade of NF-kappaB translocation by
      suppression of protein kinase R activation does not render the cell more
      susceptible to apoptosis induced by viral gene expression. (ii) A number of mRNA
      up-regulated in infected cells [e.g. IkappaBalpha (inhibitory kappaBalpha), the
      immediate-early response protein IEX-1 and c-fos] are partially degraded and not
      translated. The degradation is U(L)41-dependent and results in deadenylation,
      endonucleolytic cleavage and 3'-5' degradation. The 5'-portion resulting from the
      endonucleolytic cleavage tends to linger in the infected cells. To date, the RNAs
      processed in this manner contained ARE (AU-rich elements) in their 3'
      untranslated domains. RNAs lacking ARE were expressed and not degraded in this
      manner. (iii) Tristetraprolin and T-cell internal antigen-1, cellular proteins
      involved in the degradation of ARE-containing RNAs, are induced and activated in
      infected cells and tristetraprolin interacts physically with the U(L)41 protein.

PMID- 15493992
TI  - Characterization of the cis-acting element directing perinuclear localization of
      the metallothionein-1 mRNA.
AB  - Subcellular localization of mRNAs is a key mechanism for the synthesis of
      proteins close to their site of function. The mRNA encoding MT-1 (metallothionein
      1) is localized in the perinuclear cytoplasm, where it is associated with
      cytoskeletal-bound polysomes. This localization relies on sequences present in
      the 3'-UTR (3'-untranslated region). The present study aims to characterize the
      cis-acting localization element(s) within the 3'-UTR. Using transfected cells
      expressing tagged MT-1 differing in their 3'-UTRs (deleted or mutated), the
      section(s) of this region required for directing MT-1 transcripts to the
      perinuclear cytoplasm has been investigated. Different 3'-UTRs were also used in
      UV cross-linking experiments that highlighted two distinct regions (nt 26-30 and
      66-76) necessary for the binding of a protein of approx. 50 kDa, presumably
      involved in the mRNA targeting. The poor sequence homology between the MT-1 3'
      UTR of various species, together with the bipartite nature of the required cis
      element, indicates the involvement of a particular structure in the localization
      signal. The secondary structure of the MT-1 3'-UTR was investigated using enzymic
      and chemical probing. Current structural analysis of mutant 3'-UTRs will allow
      the critical structural features of the MT-1 mRNA perinuclear localization signal
      to be defined.

PMID- 15493993
TI  - Isolation and identification of a protein binding to the localization element of
      Metallothionein-1 mRNA.
AB  - mRNA localization provides a mechanism for localized protein synthesis. mRNAs
      encoding certain proteins, including c-MYC, c-FOS, MT-1 (Metallothionein-1) and
      vimentin, are localized around the nuclei of mammalian cells and are associated
      with the cytoskeleton. Targeting of these mRNAs to the perinuclear cytoplasm is
      mediated by elements within their 3'-UTRs (3'-untranslated regions), but many of
      the trans-acting proteins remain unidentified. UV cross-linking assays using
      radiolabelled transcripts indicated that a protein of approx. 50 kDa (from the
      Chinese-hamster ovary cell extracts) bound to the MT-1 3'-UTR sequence.
      Competition experiments using unlabelled mutant 3'-UTR RNAs revealed that the
      binding of this protein is specific to localization-positive mutants. Isolation
      of a 50 kDa protein was achieved by an RNA affinity-based method in which
      biotinylated MT-1 3'-UTR RNA was anchored to paramagnetic beads. Bound proteins
      were eluted and analysed by SDS/PAGE. The 50 kDa protein was extracted from the
      gel, subjected to trypsin digestion and identified by matrix-assisted laser
      desorption/ionization-time-of-flight mass spectrometry as eukaryote elongation
      factor 1alpha.

PMID- 15493994
TI  - Pleckstrin homology domains: not just for phosphoinositides.
AB  - PH domains (pleckstrin homology domains) are the 11th most common domain in the
      human genome and are best known for their ability to target cellular membranes by
      binding specifically to phosphoinositides. Recent studies in yeast have shown
      that, in fact, this is a property of only a small fraction of the known PH
      domains. Most PH domains are not capable of independent membrane targeting, and
      those capable of doing so (approx. 33%) appear, most often, to require both
      phosphoinositide and non-phosphoinositide determinants for their subcellular
      localization. Several recent studies have suggested that small GTPases such as
      ARF family proteins play a role in defining PH domain localization. Some others
      have described a signalling role for PH domains in regulating small GTPases,
      although phosphoinositides may also play a role. These findings herald a change
      in our perspective of PH domain function, which will be significantly more
      diverse than previously supposed.

PMID- 15493995
TI  - Lipid rafts clustering and signalling by listeriolysin O.
AB  - Listeriolysin O, the major virulent determinant of Listeria monocytogenes, is
      known for forming pores on cholesterol-rich membranes. In the present study, we
      reveal its other facet, rafts clustering. By immunofluorescence microscopy, we
      show that the glycosylphosphatidylinositol-anchored proteins CD14 and CD24, which
      normally exhibit uniform distribution on J774 cells, undergo clustering upon
      treatment with LLO. The non-raft marker transferrin receptor is unaffected by
      such treatment. Rafts clustering might explain the induction of tyrosine
      phosphorylation observed on LLO-treated cells.

PMID- 15493996
TI  - p97 and close encounters of every kind: a brief review.
AB  - The AAA (ATPase associated with various cellular activities) ATPase, p97, is a
      hexameric protein of chaperone-like function, which has been reported to interact
      with a number of proteins of seemingly unrelated functions. For the first time,
      we report a classification of these proteins and aim to elucidate any common
      structural or functional features they may share. The interactors are grouped
      into those containing ubiquitin regulatory X domains, which presumably bind to
      p97 in the same way as the p47 adaptor, and into non-ubiquitin regulatory X
      domain proteins of different functional subgroups that may employ a different
      mode of interaction (assuming they also bind directly to p97 and are not
      experimental artifacts). Future studies will show whether interacting proteins
      direct p97 to different cellular pathways or a common one and structural
      elucidation of these interactions will be crucial in understanding these
      underlying functions.

PMID- 15493997
TI  - Structural features of the low-density lipoprotein receptor facilitating ligand
      binding and release.
AB  - The LDLR (low-density lipoprotein receptor) is a modular protein built from
      several distinct structural units: LA (LDLR type-A), epidermal growth factor-like
      and beta-propeller modules. The low pH X-ray structure of the LDLR revealed long
      range intramolecular contacts between the propeller domain and the central LA
      repeats of the ligand-binding domain, suggesting that the receptor changes its
      overall shape from extended to closed, in response to pH. Here we discuss how the
      LDLR uses flexibility and rigidity of linkers between modules to facilitate
      ligand binding and low-pH ligand release.

PMID- 15493998
TI  - The anaphase-promoting complex (APC): the sum of its parts?
AB  - The APC (anaphase-promoting complex) is a multisubunit E3 ubiquitin ligase that
      targets cell-cycle-related proteins for degradation by the 26 S proteasome. The
      APC contains at least 13 subunits and is regulated by the binding of co-activator
      proteins and by phosphorylation. It is not known why the APC contains 13 subunits
      when many other ubiquitin ligases are small single-subunit enzymes. In the
      present study, the structures and functions of individual APC subunits are
      discussed. By dissecting the roles of its parts, we hope to gain insight into the
      mechanism of the intact APC.

PMID- 15493999
TI  - Structural and functional studies of mutations affecting the UBA domain of SQSTM1
      (p62) which cause Paget's disease of bone.
AB  - Mutations affecting the UBA (ubiquitin-associated) domain of SQSTM1 (Sequestosome
      1) (p62) are a common cause of Paget's disease of bone. The missense mutations
      resolve into those which retain [P392L (Pro(392)-->Leu), G411S] or abolish
      (M404V, G425R) the ability of the isolated UBA domain to bind Lys-48-linked
      polyubiquitin. These effects can be rationalized with reference to the solution
      structure of the UBA domain, which we have determined by NMR spectroscopy. The
      UBA domain forms a characteristic compact three-helix bundle, with a hydrophobic
      patch equivalent to that previously implicated in ubiquitin binding by other UBA
      domains. None of the mutations affect overall folding of the UBA domain, but both
      M404V and G425R involve residues in the hydrophobic patch, whereas Pro-392 and
      Gly-411 are more remote. A simple model assuming the isolated UBA domain is
      functioning as a compact monomer can explain the effects of the mutations on
      polyubiquitin binding. The P392L and G411S mutations do however have subtle local
      effects on secondary structure, which may become more relevant in full-length
      SQSTM1. Identification of the in vivo ubiquitylated substrates of SQSTM1 will be
      most informative in determining the functional significance of the SQSTM1
      ubiquitin interaction, and consequences of the disease-associated mutations.

PMID- 15494000
TI  - HAUSP/USP7 as an Epstein-Barr virus target.
AB  - USP7 (also called HAUSP) is a de-ubiquitinating enzyme recently identified as a
      key regulator of the p53-mdm2 pathway, which stabilizes both p53 and mdm2. We
      have discovered that the Epstein-Barr nuclear antigen 1 protein of Epstein-Barr
      virus binds with high affinity to USP7 and disrupts the USP7-p53 interaction. The
      results have important implications for the role of Epstein-Barr nuclear antigen
      1 in the cellular immortalization that is typical of an Epstein-Barr virus latent
      infection.

PMID- 15494001
TI  - Mechanisms of elongation on the ribosome: dynamics of a macromolecular machine.
AB  - Protein synthesis in the cell is performed on ribosomes, large ribonucleoprotein
      particles, which in bacteria consist of three RNA molecules and over 50 proteins.
      This review summarizes recent progress in understanding the mechanisms of the
      elongation phase of protein synthesis. Results from rapid kinetic analysis of
      elongation reactions are discussed in the light of recent structural data.

PMID- 15494002
TI  - X-ray crystallographic studies for ligand-protein interaction changes in
      rhodopsin.
AB  - G-protein-coupled receptors constitute the largest transmembrane receptor family
      in human. They are generally activated on binding their specific ligands at the
      extracellular side of membranes. The signal carried by an agonist is then
      transmitted to the intracellular side through a conformational change of the
      receptor, which becomes competent to catalyse GDP/GTP exchange in the alpha
      subunit of heterotrimeric G-protein. Since most of the G-protein-coupled
      receptors (rhodopsin-like subfamily) share a set of conserved amino acid residues
      in the transmembrane domain, it is probable that the ligand-triggered activation
      process involves a common mechanism of rearrangement of the hepta-helical
      transmembrane bundle. For understanding the nature of this event that is not yet
      characterized sufficiently, X-ray crystallographic studies of rhodopsin with or
      without light stimulation can provide valuable information. In rhodopsin, the
      initial cis-trans photoisomerization of retinal chromophore triggers the
      structural changes of transmembrane helices. This activation process has been
      characterized with some spectroscopically distinct photoreaction intermediates
      (batho, lumi, Meta I and Meta II). With recent advances in the conditions for
      crystallographic experiments, the diffraction limit of the rhodopsin crystals has
      been substantially extended. As a result, it becomes possible to detect small
      structural changes evoked after photoactivation under cryogenic conditions.

PMID- 15494003
TI  - Active and inactive conformations of the epidermal growth factor receptor.
AB  - The members of the EGFR (epidermal growth factor receptor) family of RTKs
      (receptor tyrosine kinases), also known as the ErbB or HER family, have been
      implicated in many human cancers. Structural studies of the EGFR extracellular
      region (sEGFR) have led to the proposal of a novel mechanism for ligand-induced
      receptor dimerization. In this model EGF binding induces a dramatic
      conformational change in EGFR, exposing a dimerization site that is normally
      occluded in the inactivated conformation, and thus promoting the formation of an
      entirely receptor-mediated dimer. It is well established that antibodies against
      the extracellular region of EGFR that prevent ligand binding and/or receptor
      signalling can inhibit tumour growth in vivo. At least five such anti-EGFR
      antibodies are currently in clinical trials and one, C225/cetuximab (Erbitux),
      was recently approved in the U.S. and Europe for use in advanced colorectal
      cancers. Recent structural studies of ErbB2 in complex with anti-ErbB2 antibodies
      (trastuzumab/Herceptin and pertuzumab/Omnitarg) have provided significant
      insights into how these drugs function. There have been no such studies for
      similar EGFR-targeted drugs to date. The implications of this model for the
      possible mechanisms of antibody-mediated inhibition of EGFR are discussed.

PMID- 15494004
TI  - Characterization of simian virus 40 on its infectious entry pathway in cells
      using fluorescence correlation spectroscopy.
AB  - SV40 (simian virus 40) is a double-stranded DNA virus and is strongly oncogenic
      in experimental animals. SV40 enters cells by atypical endocytosis mediated by
      caveolae, transporting the virus to its usual destination, namely the endoplasmic
      reticulum. The cellular mechanisms of capsid disassembly (uncoating) and
      deliverance of the viral genome into the cellular nucleus remain unknown. Here,
      we study (i) the formation of caveolae after viral infection and the diffusion of
      caveosome vesicles in the cytoplasm and (ii) the capsid disassembly and the
      mobility of the viral genome on its way to the nucleus, using fluorescence
      correlation spectroscopy. To follow the viral genome and capsids separately, the
      histone components of SV40 minichromosomes were labelled with enhanced yellow
      fluorescent protein and the capsid was labelled with a fluorescent red dye,
      Alexa568. We characterized the diffusion of caveosomes, the capsid disassembly
      process in the cytoplasm and the mobility of the viral genome in the nucleus,
      using two kinds of permissive cells.

PMID- 15494005
TI  - Activation of the blood-brain barrier by SIV (simian immunodeficiency virus)
      requires cell-associated virus and is not restricted to endothelial cell
      activation.
AB  - The primary cell infected during acute HIV neuropathogenesis is the monocyte
      derived macrophage. We have demonstrated that there is activation of the BBB
      (blood-brain barrier) during acute viral infection and at terminal AIDS. However,
      it has never been determined if there is a requirement for the virus to be
      carried through the BBB or how these Trojan horses would be induced to cross the
      BBB. We added SIVmac251-infected (SIV is simian immunodeficiency virus)
      mononuclear cells (and their supernatants) to the luminal or abluminal
      compartment of our BBB model. There was activation of both sides of the BBB
      model, only if viral-infected cells were added to the luminal compartment, as
      opposed to the addition of cell-free supernatants. This suggests that cell
      associated virus is essential for the activation of the BBB. This, in turn, would
      be expected to lead to further infiltration of cells capable of viral infection.
      VCAM-1 (vascular cell adhesion molecule 1) staining revealed, for the first time,
      that there is an absolute requirement for virally infected cells, and not just
      the presence of virus for the activation of the BBB.

PMID- 15494006
TI  - Fluorescence studies of single biomolecules.
AB  - Single-molecule fluorescence has the capability to detect properties buried in
      ensemble measurements and, hence, provides new insights about biological
      processes. Ratiometric methods are normally used to reduce the effects of
      excitation beam inhomogeneity. Fluorescence resonance energy transfer is widely
      used but there are problems in inserting the fluorophores in the correct position
      on the biomolecule, particularly if the structure is not known. We have recently
      developed two-colour coincidence single-molecule fluorescence that addresses this
      problem. This method can be used to determine quantitatively the multimerization
      states of biomolecules, in solution without separation. The future prospects of
      single-molecule fluorescence as applied to biological molecules are discussed.

PMID- 15494007
TI  - The effect of force on thermodynamics and kinetics: unfolding single RNA
      molecules.
AB  - We have used laser tweezers to unfold single RNA molecules at room temperature
      and in physiological-type solvents. The forces necessary to unfold the RNAs are
      over the range 10-20 pN, forces that can be generated by cellular enzymes. The
      Gibbs free energy for the unfolding of TAR (transactivation-responsive) RNA from
      HIV was found to be increased after the addition of argininamide; the TAR hairpin
      was stabilized. The rate of unfolding was decreased and the rate of folding was
      increased by argininamide.

PMID- 15494008
TI  - Single protein molecular dynamics determined with ultra-high precision.
AB  - We have successfully observed dynamical Brownian motions in an individual protein
      molecule and other biological ones in real-time with one-hundredth the atomic
      scale precision (picometer-scale precision) using X-rays of the super photon ring
      8 (SPring-8).

PMID- 15494009
TI  - N-glycosylated catalytic unit meets O-glycosylated propeptide: complex protein
      architecture in a fungal hexosaminidase.
AB  - beta-N-Acetylhexosaminidase from a filamentous fungus Aspergillus oryzae is a
      secreted enzyme known to be an important component of the binary chitinolytic
      system. Cloning of the hexA gene and sequencing of the enzyme revealed its unique
      preproprotein structure. While the enzyme's zincin-like and catalytic domain had
      significant similarities with members of the glycohydrolase 20 family, the
      propeptide was unique for the fungal enzyme. Detailed pulse-chase and inhibition
      studies revealed that propeptide was processed during the biosynthesis of the
      enzyme. Moreover, the presence of propeptide was necessary for enzyme activation,
      dimerization and secretion. The catalytic unit was N-glycosylated, and the
      propeptide was O-glycosylated, both in their C-terminal parts. Deglycosylation
      experiments revealed that the N-glycosylation increased the stability and
      solubility of the enzyme. In contrast, O-glycosylated propeptide was necessary to
      attain the full enzymic activity.

PMID- 15494010
TI  - The N-glycan glucosidase system in Trypanosoma brucei.
AB  - Reactions involving removal and addition of glucose to N-glycans in the ER
      (endoplasmic reticulum) are performed in higher eukaryotes by glucosidases I and
      II and the UDP-glucose:glycoprotein glucosyltransferase respectively.
      Monoglucosylated N-glycan structures have been implicated in glycoprotein folding
      or ER quality control. Components of the system appear across a range of
      organisms; however, the precise combination differs between organisms. We have
      identified putative components of the system in the protozoal organism
      Trypanosoma brucei by local alignment searching. The function of one of these
      components, a glucosidase II alpha-subunit homologue, has been confirmed by
      phenotyping a null mutant, and an ectopic expression cell line. A combination of
      MS, methylation linkage analysis, exoglycosidase digestion and partial acetolysis
      have been used to characterize three novel N-glycan structures on the variant
      surface glycoprotein of the null mutant. On the basis of our results, we propose
      that two N-glycan precursors are available for transfer to variant surface
      glycoprotein (variant 221) in the ER of T. brucei; only one of these precursors
      is glucosylated after transfer.

PMID- 15494011
TI  - Molecular mechanisms in clathrin-mediated membrane budding revealed through
      subcellular proteomics.
AB  - Subcellular proteomics is a powerful new approach that combines subcellular
      fractionation and MS (mass spectrometry) to identify the protein complement of
      cellular compartments. The approach has been applied to isolated organelles and
      major suborganellar structures and each study has identified known proteins not
      previously understood to associate with the compartment and novel proteins that
      had been described only as predicted open-reading frames from genome sequencing
      data. We have utilized subcellular proteomics to analyse the protein components
      of CCVs (clathrin-coated vesicles) isolated from adult brain. Accounting for
      identified fragmented peptides allows for a quantitative assessment of protein
      complexes associated with CCVs, and the identification of many of the known
      components of post-fusion synaptic vesicles demonstrates that a main function for
      brain CCVs is to recycle synaptic vesicles. In addition, we have identified a
      number of novel proteins that participate in CCV formation and function at the
      trans-Golgi network and the plasma membrane. Characterization of two of these
      proteins, NECAP1 and NECAP2, has led to the identification of a new consensus
      motif that mediates protein interactions with the clathrin adaptor protein 2.
      These studies highlight the ability of proteomics to reveal new insights into the
      mechanisms and functional roles of subcellular compartments.

PMID- 15494012
TI  - Moving proteins from the cytosol into mitochondria.
AB  - Mitochondria of the yeast Saccharomyces cerevisiae contain at least 750 different
      proteins, which perform diverse roles. Most of these proteins (approx. 99%) are
      translated on cytosolic ribosomes, and their import into mitochondria is
      essential for mitochondrial function. Proteinaceous machineries of great
      complexity, the so-called translocases, in the mitochondrial membranes mediate
      the import of these proteins.

PMID- 15494013
TI  - Mass spectrometry is a powerful tool for identification of proteins associated
      with lipid rafts of Jurkat T-cell line.
AB  - Many proteins involved in signal-transduction pathways are concentrated in
      membrane microdomains enriched in lipids with distinct physical properties. Since
      these microdomains are insoluble in non-ionic detergents in cold, proteins
      associated with them could be efficiently purified by techniques such as sucrose
      density gradient centrifugation. The complexity of the resulting protein mixture
      requires powerful MS technique for its analysis. We have found that successful
      identification of biologically relevant proteins is critically dependent on the
      enrichment of the starting material (plasma membranes), and on the extraction
      procedure. Applying these conditions in combination with microHPLC-ESI
      (electrospray ionization)-MS/MS, we have identified proteins involved in
      signalling, cytoskeletal association and cellular adhesion in Jurkat cells that
      are not stimulated by any antibody incubation.

PMID- 15494014
TI  - BCR activation of PI3K is Vav-independent in murine B cells.
AB  - BCR (B-cell antigen receptor)-induced Ca(2+) signalling is initiated by
      activation of tyrosine kinases, which in concert with adaptor proteins and lipid
      kinases regulate PLC (phospholipase C) gamma2 activation. Vav and PI3K
      (phosphoinositide 3-kinase) are required for optimal Ca(2+) responses, although
      it has not been established, in primary B-cells, if both proteins are components
      of the same pathway. In vitro evidence suggests that binding of the PI3K lipid
      product PIP3 to Vav pleckstrin homology domain contributes to Vav activation.
      However, pharmacological inhibition of PI3K by wortmannin or deletion of the
      p110delta catalytic subunit has no effect on Vav activation in response to BCR
      engagement, suggesting that this mechanism does not operate in vivo. We also show
      that PI3K recruitment to phosphorylated-tyrosine-containing complexes is Vav
      independent. Taken together with our previous observation that protein kinase B
      phosphorylation is normal in Vav-deficient B-cells, we suggest that PI3K
      activation is Vav-independent in response to strong signals delivered by
      multivalent cross-linking.

PMID- 15494015
TI  - The role of SHIP1 in macrophage programming and activation.
AB  - The SHIP1 (SH2-containing inositol-5'-phosphatase 1) acts as a negative regulator
      of proliferation, survival and end cell activation in haemopoietic cells. It does
      so, at least in part, by translocating to membranes after extracellular
      stimulation and hydrolysing the phosphoinositide 3-kinase-generated second
      messenger, PtdIns(3,4,5)P(3) to PtdIns(3,4)P(2). SHIP1(-/-) mice have, as a
      result, an increased number of neutrophils and monocyte/macrophages because their
      progenitors display enhanced survival and proliferation. These mice also suffer
      from osteoporosis because of an increased number of hyperactive osteoclasts and a
      significant neutrophil infiltration of the lungs. Interestingly, SHIP1(-/-) mice
      do not display endotoxin tolerance and we have found that lipopolysaccharide
      induced endotoxin tolerance is contingent on up-regulating SHIP1, through the
      production of autocrine-acting transforming growth factor-beta, in bone-marrow
      derived macrophages and mast cells. Intriguingly, unlike bone-marrow-derived
      macrophages, SHIP1(-/-) peritoneal and alveolar macrophages produce 10-fold less
      NO than wild-type macrophages because these in vivo-generated macrophages have
      very high arginase I levels and this enzyme competes with inducible nitric oxide
      synthase for the substrate L-arginine. It is probable that, in the face of
      chronically increased PtdIns(3,4,5)P(3) levels in their myeloid progenitors,
      SHIP1(-/-) mice display a skewed development away from M1 (killer) macrophages
      (which have high inducible nitric oxide synthase levels and produce NO to kill
      microorganisms and tumour cells), towards M2 (healing) macrophages (which have
      high arginase levels and produce ornithine to promote host-cell growth and
      collagen formation). This skewing probably occurs to avoid septic shock and
      suggests that the phosphoinositide 3-kinase pathway plays a critical role in
      programming macrophages.

PMID- 15494016
TI  - The p110delta subunit of phosphoinositide 3-kinase is required for the
      lipopolysaccharide response of mouse B cells.
AB  - PI3K (phosphoinositide 3-kinase) I(A) family members contain a regulatory subunit
      and a catalytic subunit. The p110delta catalytic subunit is expressed
      predominantly in haematopoietic cells. There, among other functions, it regulates
      antigen receptor-mediated responses. Using mice deficient in the p110delta
      subunit of PI3K, we investigated the role of this subunit in LPS
      (lipopolysaccharide)-induced B cell responses, which are mediated by Toll-like
      receptor 4 and RP105. After injection of DNP-LPS (where DNP stands for 2,4
      dinitrophenol), p110delta(-/-) mice produced reduced levels of DNP-specific IgM
      and IgG when compared with wild-type mice. In vitro, the proliferation and up
      regulation of surface activation markers such as CD86 and CD25 induced by LPS and
      an antibody against RP105 were decreased. We analysed the activation state of key
      components of the LPS pathway in B cells to determine whether there was a defect
      in signalling in p110delta(-/-) B cells. They showed normal extracellular-signal
      regulated kinase phosphorylation, but anti-RP105-induced protein kinase B,
      IkappaB (inhibitor of nuclear factor kappaB) and c-Jun N-terminal kinase
      activation was severely reduced. This demonstrates that the p110delta subunit of
      PI3K is involved in the LPS response in B cells and may represent a link between
      the innate and the adaptive immune system.

PMID- 15494017
TI  - PDE6 is an effector for the Wnt/Ca2+/cGMP-signalling pathway in development.
AB  - Wnt signalling in development operates via members of the Frizzleds, G-protein
      coupled receptors that bind specific Wnt ligands and mediate signalling via
      distinct pathways. The Wnt/Ca(2+)/cGMP pathway mediated by Frizzled-2 was
      discovered recently. Activation of this pathway leads to increased intracellular
      concentrations of Ca(2+) and decreased intracellular concentrations of cGMP. The
      nature of the phosphodiesterase responsible for this Frizzled-2-mediated effect
      on cGMP levels was identified based on three separate criteria: (i) sensitivity
      to selective enzyme inhibitors, (ii) behaviour on chromatographic separation, and
      (ii) isolation by two-dimensional gels in tandem with direct mapping by MS of
      tryptic digests of the activity. On the basis of results from these three
      analyses, the cGMP-specific phosphodiesterase, PDE6, is demonstrated to be an
      effector for the Wnt/Ca(2+)/cGMP signalling pathway of development, which is
      mediated by Frizzled-2.

PMID- 15494018
TI  - Plakoglobin expression and localization in zebrafish embryo development.
AB  - Plakoglobin (gamma-catenin) and beta-catenin are major components of the adherens
      junctions and can be localized to the nucleus by activation of the Wnt signalling
      pathway. In addition, plakoglobin is also found in desmosomes, a vertebrate
      specific cell-cell adhesion structure. Plakoglobin expression and localization
      were examined at the protein level during zebrafish embryonic development by
      Western blotting and confocal microscopy. Plakoglobin was expressed throughout
      embryo development at the protein level. Western blotting revealed that embryonic
      plakoglobin protein content increased between 12- and 24-h post-fertilization
      (hpf). Confocal microscopy showed that at stages up to 12 hpf, plakoglobin and
      beta-catenin were co-localized and expressed in both the nucleus and in cell-cell
      junctions. At 24- and 72-hpf, separate patterns were seen for plakoglobin and
      beta-catenin. These data indicate that plakoglobin localization in the heart
      region shifts from adherens junctions to desmosomes during heart chamber
      development.

PMID- 15494019
TI  - A molecular cell biology of lithium.
AB  - Lithium (Li(+)), a mood stabilizer, has profound effects on cultured neurons,
      offering an opportunity to investigate its cellular biological effects. Here we
      consider the effect of Li(+) and other psychotropic drugs on growth cone
      morphology and chemotaxis. Li(+) inhibits GSK-3 (glycogen synthase kinase-3) at a
      therapeutically relevant concentration. Treated cells show a number of features
      that arise due to GSK-3 inhibition, such as altered microtubule dynamics, axonal
      branching and loss of semaphorin 3A-mediated growth cone collapse. Li(+) also
      causes growth cones to spread; however, a similar effect is seen with two other
      mood stabilizers, valproic acid and carbamazepine, but without changes in
      microtubules or axon branching. This common effect of mood stabilizers is
      mediated by changes in inositol phosphate signalling, not GSK-3 activity. Given
      the presence of neurogenesis in the adult brain, we speculate that changes in
      growth cone behaviour could also occur during treatment of mental disorders.

PMID- 15494021
TI  - Glycogen synthase kinase 3beta and the regulation of axon growth.
AB  - One of the earliest hallmarks that distinguish growing axons from dendrites is
      their growth rate; axons grow faster than dendrites. In vertebrates, where axons
      are required to grow for considerable distances, particularly in the peripheral
      nervous system, a fast axon growth rate is a requisite property. In neurons that
      respond to the neurotrophin growth factor/nerve growth factor with increased axon
      growth rates, two distinct intracellular signalling pathways are recruited: the
      MAPK (mitogen-activated protein kinase) pathway and the phosphatidylinositol-3
      kinase pathway. The activation of either pathway leads to changes in microtubule
      dynamics within growing axons and growth cones and these underlie fast axon
      growth rates. Microtubule dynamics is regulated by microtubule-associated
      proteins and in the MAPK pathway this function is subserved by microtubule
      associated protein 1B, whereas in the phosphatidylinositol-3 kinase pathway,
      adenomatous polyposis coli is the regulating microtubule-associated protein.

PMID- 15494020
TI  - Glycogen synthase kinase-3 in insulin and Wnt signalling: a double-edged sword?
AB  - Glycogen synthase kinase-3 is an unusual protein serine/threonine kinase that,
      unlike most of its 500-odd relatives in the genome, is active under resting
      conditions and is inactivated upon cell stimulation. The two mammalian isoforms,
      GSK-3alpha and beta, play largely overlapping roles and have been implicated in a
      variety of human pathologies, including Type II diabetes, Alzheimer's disease,
      bipolar disorder and cancer. Recently, the modes of regulation of this enzyme
      have been elucidated through a combination of structural and cell biological
      studies. A series of relatively selective small molecules have facilitated
      chemical manipulation of the enzyme in intact cells and tissues, and new roles
      for the protein kinase in embryonic stem cell differentiation and motility have
      emerged. Despite these advances, the therapeutic value of this enzyme as a drug
      target remains clouded by uncertainty over the potential of antagonists to
      promote tumorigenesis. This article describes the state of understanding of this
      intriguing enzyme, and weighs current evidence regarding whether there is a
      therapeutic window for amelioration of diseases in which it is implicated, in the
      absence of inducing new pathologies.

PMID- 15494022
TI  - Uncoupling insulin signalling by serine/threonine phosphorylation: a molecular
      basis for insulin resistance.
AB  - Insulin resistance refers to a decreased capacity of circulating insulin to
      regulate nutrient metabolism. Recent studies reveal that agents that induce
      insulin resistance exploit phosphorylation-based negative feedback control
      mechanisms otherwise utilized by insulin itself to uncouple the insulin receptor
      from its downstream effectors and thereby terminate insulin signal transduction.
      This article focuses on the Ser/Thr protein kinases which phosphorylate insulin
      receptor substrates and the major Ser sites that are phosphorylated, as key
      elements in the uncoupling of insulin signalling and the induction of an insulin
      resistance state.

PMID- 15494023
TI  - Analysis of insulin signalling by RNAi-based gene silencing.
AB  - Using siRNA-mediated gene silencing in cultured adipocytes, we have dissected the
      insulin-signalling pathway leading to translocation of GLUT4 glucose transporters
      to the plasma membrane. RNAi (RNA interference)-based depletion of components in
      the putative TC10 pathway (CAP, CrkII and c-Cbl plus Cbl-b) or the phospholipase
      Cgamma pathway failed to diminish insulin signalling to GLUT4. Within the
      phosphoinositide 3-kinase pathway, loss of the 5'-phosphatidylinositol 3,4,5
      trisphosphate phosphatase SHIP2 was also without effect, whereas depletion of the
      3'-phosphatase PTEN significantly enhanced insulin action. Downstream of
      phosphatidylinositol 3,4,5-trisphosphate and PDK1, silencing the genes encoding
      the protein kinases Akt1/PKBalpha, or CISK(SGK3) or protein kinases Clambda/zeta
      had little or no effect, but loss of Akt2/PKBbeta significantly attenuated GLUT4
      regulation by insulin. These results show that Akt2/PKBbeta is the key downstream
      intermediate within the phosphoinositide 3-kinase pathway linked to insulin
      action on GLUT4 in cultured adipocytes, whereas PTEN is a potent negative
      regulator of this pathway.

PMID- 15494024
TI  - Mechanisms of integration of cells and extracellular matrices by integrins.
AB  - While it is self-evident that all extracellular molecules are an integral part of
      a multicellular organism, it is paradoxical that they are often considered to be
      dissociated from cells. The reality is that a continuum of dynamic, bi
      directional interactions links the intracellular environment through cell-surface
      receptors to multimolecular extracellular assemblies. These interactions not only
      control the behaviour of individual cells, but also determine tissue
      architecture. Adhesion receptor function is partly determined by an ability to
      tether the contractile cytoskeleton to the plasma membrane, but there is also
      evidence that integrin receptors modulate signalling events that are essential
      for cellular differentiation. A major challenge is now to integrate work at the
      atomic, molecular and cellular levels, and obtain holistic insights into the
      mechanisms controlling cell adhesion. In the present study, we review current
      knowledge of the molecular mechanisms employed by cells to integrate with the
      extracellular matrix. Two main topics are covered: the adaptation of integrin
      structure for bi-directional signalling and the integration of integrin
      signalling with other receptors.

PMID- 15494025
TI  - Physical and functional interaction between integrins and hERG potassium
      channels.
AB  - Integrins are adhesion receptors capable of transmitting intracellular signals
      that regulate many different cellular functions. Among integrin-mediated signals,
      the activation of ion channels can be included. We demonstrated that a long
      lasting activation of hERG (human ether-a-go-go-related gene) potassium channels
      occurs in both human neuroblastoma and leukaemia cells after the activation of
      the beta1 integrin subunit. This activation is apparently a determining factor
      inducing neurite extension and osteoclastic differentiation in both the cell
      types. More recently, we provided evidences that beta1 integrins and hERG
      channels co-precipitate in both the cell types. Preliminary results suggest that
      a macromolecular signalling complex indeed occurs between integrins and the hERG1
      protein and that hERG channel activity can modulate integrin downstream
      signalling.

PMID- 15494026
TI  - Crumbs homologue 1 in polarity and blindness.
AB  - Several retinal dystrophies, including retinitis pigmentosa type 12 and Leber
      congenital amaurosis, are caused by a large variety of mutations in the CRB1
      (Crumbs homologue 1) gene. This discovery led to an increased focus on the
      function of CRB1 and the Drosophila homologue Crumbs. In the present study, we
      review the current knowledge on Crumbs and its vertebrate homologues, their
      function in cell polarity and their pathogenicity in retinal degeneration.

PMID- 15494027
TI  - Cytoskeletal proteins talin and vinculin in integrin-mediated adhesion.
AB  - The cytoskeletal proteins talin and vinculin form part of a macromolecular
      complex on the cytoplasmic face of integrin-mediated cellular junctions with the
      extracellular matrix. Recent genetic, biochemical and structural data show that
      talin is essential for the assembly of such junctions, whereas vinculin appears
      to be important in regulating adhesion dynamics and cell migration.

PMID- 15494028
TI  - The integrity of cholesterol-enriched microdomains is essential for the
      constitutive high activity of protein kinase B in tumour cells.
AB  - A deregulated activity of PKB/Akt (where PKB stands for protein kinase B) renders
      tumour cells resistant to a variety of apoptosis-inducing stimuli. Elucidation of
      the mechanisms responsible for this deregulation is of prime importance for the
      development of novel anti-cancer drugs. Results of the present study demonstrate
      that the constitutive activity of PKB/Akt in B16BL6 melanoma cells depends on the
      integrity of cholesterol-enriched membrane microdomains, since the exposure of
      cells to cholesterol-depleting agents decreases the phosphorylation of this
      enzyme, with no change in its total protein level. Inhibitors of Hsp90 (heat
      shock protein 90) decreased phosphorylation of PKB/Akt with a similar pattern.
      Dephosphorylation of the enzyme, as a consequence of raft disintegration, could
      be precluded by inhibition of serine/threonine (but not tyrosine) phosphatases.
      Our results imply that destabilization of lipid rafts seemingly affects the
      association of Hsp90 with the respective serine/threonine phosphatases, thereby
      increasing the accessibility to PKB/Akt to deactivating phosphatases. We have
      found recently that reconstituted expression of H-2K class I glycoproteins in
      class I-deficient B16BL6 cells also decreases the phosphorylation of PKB/Akt.
      Therefore it is possible that raft-associated regulation of this important enzyme
      involves both H-2K glycoproteins and Hsp90.

PMID- 15494029
TI  - Regulation of cellular processes by PPARgamma ligands in neuroblastoma cells is
      modulated by the level of retinoblastoma protein expression.
AB  - Neuroblastoma is a childhood cancer, which spontaneously regresses. This has led
      to a search for agents that mimic this process. We show that both natural and
      synthetic ligands of PPARgamma (peroxisome-proliferator-activated receptor gamma)
      inhibit the growth of neuroblastoma cells in vitro. The degree of PPAR activation
      was attenuated however in the presence of the retinoblastoma protein. Addition of
      trichostatin A, a histone deacetylase inhibitor, abolished retinoblastoma protein
      repression of PPAR activity. Moreover, enhanced growth inhibition was observed
      when neuroblastoma cells were treated with a PPARgamma ligand and a histone
      deacetylase inhibitor, suggesting a combination therapy to treat neuroblastoma
      might prove more effective than using either agent alone.

PMID- 15494030
TI  - Heterodimers and family-B GPCRs: RAMPs, CGRP and adrenomedullin.
AB  - RAMPs (receptor activity-modifying proteins) are single-pass transmembrane
      proteins that associate with certain family-B GPCRs (G-protein-coupled
      receptors). Specifically for the CT (calcitonin) receptor-like receptor and the
      CT receptor, this results in profound changes in ligand binding and receptor
      pharmacology, allowing the generation of six distinct receptors with preferences
      for CGRP (CT gene-related peptide), adrenomedullin, amylin and CT. There are
      three RAMPs: RAMP1-RAMP3. The N-terminus appears to be the main determinant of
      receptor pharmacology, whereas the transmembrane domain contributes to
      association of the RAMP with the GPCR. The N-terminus of all members of the RAMP
      family probably contains two disulphide bonds; a potential third disulphide is
      found in RAMP1 and RAMP3. The N-terminus appears to be in close proximity to the
      ligand and plays a key role in its binding, either directly or indirectly.
      BIBN4096BS, a CGRP antagonist, targets RAMP1 and this gives the compound very
      high selectivity for the human CGRP(1) receptor.

PMID- 15494031
TI  - Dimerization of alpha1-adrenoceptors.
AB  - Three distinct genes encode alpha(1)-adrenoceptors. Although homodimers of each
      subtype have been reported, certain but not all combinations of heterodimers of
      the alpha(1)-adrenoceptors appear to form. Key studies in this field are reviewed
      and the approaches that have been applied to monitoring the selectivity and the
      basis of alpha(1)-adrenoceptor dimerization are discussed.

PMID- 15494032
TI  - GPCR-interacting proteins (GIPs): nature and functions.
AB  - The simplistic idea that seven transmembrane receptors are single monomeric
      proteins that interact with heterotrimeric G-proteins after agonist binding is
      definitively out of date. Indeed, GPCRs (G-protein-coupled receptors) are part of
      multiprotein networks organized around scaffolding proteins. These GIPs (GPCR
      interacting proteins) are either transmembrane or cytosolic proteins. Proteomic
      approaches can be used to get global pictures of these 'receptosomes'. This
      approach allowed us to identify direct but also indirect binding partners of
      serotonin receptors. GIPs are involved in a wide range of functions including
      control of the targeting, trafficking and signalling of GPCRs. One of them,
      Shank, which is a secondary and tertiary partner of metabotropic and ionotropic
      glutamate receptors, respectively, can induce the formation of a whole functional
      glutamate 'receptosome' and the structure to which it is associated, the
      dendritic spine.

PMID- 15494033
TI  - Hetero-oligomers of alpha2A-adrenergic and mu-opioid receptors do not lead to
      transactivation of G-proteins or altered endocytosis profiles.
AB  - Complexes of alpha(2A)-ARs (alpha(2A)-adrenergic receptors) and MORs (mu-opioid
      receptors), probably hetero-oligomers, were detected by co-immunoisolation after
      extraction from HEK-293 cells (human embryonic kidney 293 cells). Functional
      communication between these receptors is revealed by alpha(2A)-AR activation of a
      pertussis toxin-insensitive G(i)alpha subunit (termed as G(i)1) when fused with
      the MOR and evaluated in membranes from pertussis toxin-treated cells. However,
      the alpha(2A)-AR does not require transactivation through MOR, since
      quantitatively indistinguishable results were observed in cells co-expressing
      alpha(2A)-AR and a fusion protein of G(i)1 with the first transmembrane span of
      MOR (myc-MOR-TM1). Functional cross-talk among these alpha(2A)-AR-MOR complexes
      does not occur for internalization profiles; incubation with adrenaline
      (epinephrine) leads to endocytosis of alpha(2A)-AR but not MOR, while incubation
      with DAMGO ([D-Ala,NMe-Phe,Gly-ol]enkephalin) leads to endocytosis of MOR but not
      alpha(2A)-AR in cells co-expressing both the receptors. Hence, alpha(2A)-AR and
      MOR hetero-oligomers, although they occur, do not have an obligatory functional
      influence on one another in the paradigms studied.

PMID- 15494034
TI  - AKAP (A-kinase anchoring protein) domains: beads of structure-function on the
      necklace of G-protein signalling.
AB  - AKAPs (A-kinase anchoring proteins) are members of a diverse family of scaffold
      proteins that minimally possess a characteristic binding domain for the RI/RII
      regulatory subunit of protein kinase A and play critical roles in establishing
      spatial constraints for multivalent signalling assemblies. Especially for G
      protein-coupled receptors, the AKAPs provide an organizing centre about which
      various protein kinases and phosphatases can be assembled to create solid-state
      signalling devices that can signal, be modulated and trafficked within the cell.
      The structure of AKAP250 (also known as gravin or AKAP12), based on analyses of
      milligram quantities of recombinant protein expressed in Escherichia coli,
      suggests that the AKAP is probably an unordered scaffold, acting as a necklace on
      which 'jewels' of structure-function (e.g. the RII-binding domain) that provide
      docking sites on which signalling components can be assembled. Recent results
      suggest that AKAP250 provides not only a 'tool box' for assembling signalling
      elements, but may indeed provide a basis for spatial constraint observed for many
      signalling paradigms. The spatial dimension of the integration of cell signalling
      will probably reflect many functions performed by members of the AKAP family.

PMID- 15494035
TI  - Amylin receptors: molecular composition and pharmacology.
AB  - Several receptors which bind the hormone AMY (amylin) with high affinity have now
      been identified. The minimum binding unit is composed of the CT (calcitonin)
      receptor at its core, plus a RAMP (receptor activity modifying protein). The
      receptors have been named AMY(1(a)), AMY(2(a)) and AMY(3(a)) in accordance with
      the association of the CT receptor (CT((a))) with RAMP1, RAMP2 and RAMP3
      respectively. The challenge is now to determine the localization and
      pharmacological nature of each of these receptors. Recent attempts to achieve
      these aims will be briefly discussed.

PMID- 15494036
TI  - Determining calmodulin binding to metabotropic glutamate receptors with distinct
      protein-interaction methods.
AB  - mGluRs (metabotropic glutamate receptors) are G-protein-coupled receptors that
      modulate synaptic transmission. The eight mammalian mGluRs form three groups
      based on sequence and functional similarities: group I (1 and 5), group II (2 and
      3) and group III (4, 6-8) mGluRs. In the present study, we used a Y2H (yeast two
      hybrid) screen to identify proteins that interact with the C-terminal
      intracellular tail of mGluR3. Prominent among the candidate receptor interacting
      proteins was calmodulin, a Ca(2+) sensor known to bind identifiable sequences in
      group I and III mGluRs. The Y2H method was used to investigate calmodulin binding
      to mGluRs but failed to confirm the documented interaction with group III mGluRs.
      Furthermore, subsequent biochemical analysis showed that calmodulin does not
      interact with group II mGluRs. This illustrates that certain Ca(2+)-dependent
      interactions are not recapitulated in yeast. Moreover, it highlights the
      necessity for supporting biochemical data to substantiate interactions identified
      with Y2H methods.

PMID- 15494037
TI  - Molecular mechanisms of GABA(B) receptor activation: new insights from the
      mechanism of action of CGP7930, a positive allosteric modulator.
AB  - The GABA(B) (gamma-aminobutyric acid-B) receptor is composed of two subunits,
      GABA(B1) and GABA(B2). Both subunits share structural homology with other class
      III G-protein-coupled receptors. They contain two main domains, a heptahelical
      domain typical of all G-protein-coupled receptors and a large ECD (extracellular
      domain). It has not been demonstrated whether the association of these two
      subunits is always required for function. However, GABA(B2) plays a major role in
      coupling with G-proteins, and GABA(B1) has been shown to bind GABA. To date, only
      ligands interacting with GABA(B1)-ECD have been identified. In the present study,
      we explored the mechanism of action of CGP7930, a compound described as a
      positive allosteric regulator of the GABA(B) receptor. We have shown that it can
      weakly activate the wild-type GABA(B) receptor, but also the GABA(B2) expressed
      alone, thus being the first described agonist of GABA(B2). CGP7930 retains its
      weak agonist activity on a GABA(B2) subunit deleted of its ECD. Thus the
      heptahelical domain of GABA(B2) behaves similar to a rhodopsin-like receptor.
      These results open new strategies for studying the mechanism of activation of
      GABA(B) receptor and examine any possible role of GABA(B2).

PMID- 15494038
TI  - G-protein-coupled receptor allosterism: the promise and the problem(s).
AB  - Allosteric modulators of G-protein-coupled receptors interact with binding sites
      that are topographically distinct from the orthosteric site recognized by the
      receptor's endogenous agonist. Allosteric ligands offer a number of advantages
      over orthosteric drugs, including the potential for greater receptor subtype
      selectivity and a more 'physiological' regulation of receptor activity. However,
      the manifestations of allosterism at G-protein-coupled receptors are quite
      varied, and significant challenges remain for the optimization of screening
      methods to ensure the routine detection and validation of allosteric ligands.

PMID- 15494039
TI  - Interactions between G-protein-coupled receptors and periplakin: a selective
      means to regulate G-protein activation.
AB  - A substantial number of G-protein-coupled receptor-interacting proteins have been
      identified initially by the use of yeast two-hybrid screens. Using the C-terminal
      tail of both opioid receptors and the melanin concentrating hormone receptor-1 as
      bait, the actin and intermediate filament-binding protein periplakin was
      isolated. In each case, the site of interaction is within helix VIII of the
      receptor and periplakin limits agonist-mediated G-protein activation potentially
      by competing with G-protein for this region of the receptor.

PMID- 15494040
TI  - Allosteric modulators of metabotropic glutamate receptors: lessons learnt from
      mGlu1, mGlu2 and mGlu5 potentiators and antagonists.
AB  - Although relatively few G-protein-coupled receptors are Class C, in recent years,
      this small family of receptors has become a focal point for the discovery of new
      and exciting allosteric modulators. The mGlu (metabotropic glutamate) receptors
      are illustrative in the discovery of both positive and/or negative allosteric
      modulators with unique pharmacological properties. For instance, allosteric
      modulators of the mGlu2 receptor act as potentiators of glutamate responses in
      clonal expression systems and in native tissue assays. These potentiators act to
      increase the affinity of orthosteric agonists for the mGlu2 receptor and shift
      potency curves for the agonist to the left. In electrophysiological experiments,
      the potentiators show a unique activation-state-dependent presynaptic inhibition
      of glutamate release and significantly enhance the receptor-mediated increase in
      G-protein binding, as seen with autoradiography. Similarly, potentiators of mGlu5
      have been described, as well as allosteric antagonists or inverse agonists of
      mGlu1 and mGlu5. Binding and activity of the modulators have recently indicated
      that positive and negative allosteric sites can be, but are not necessarily,
      overlapping. Compared with orthosteric ligands, these modulators display a unique
      degree of subtype selectivity within the highly conserved mGlu family of
      receptors and can have very distinct pharmacological properties, such as neuronal
      frequency-dependent activity. This short review describes some of the unique
      features of these mGlu1, mGlu2 and mGlu5 allosteric modulators.

PMID- 15494041
TI  - G-protein-coupled receptor accessory proteins: their potential role in future
      drug discovery.
AB  - Historically, the activation and inhibition of GPCR (G-protein-coupled receptor)
      function have been a very successful avenue for drug discovery and development.
      However, it is clear that receptors do not function in isolation but are impacted
      by other proteins. These proteins may alter either binding or functional
      responses. Identification and study of these interactions have grown rapidly in
      recent years and continue to do so, resulting in a plethora of potential receptor
      protein connections. These associations can be regarded as alternative
      intervention points to modulate GPCR function and may not only provide
      alternative ways to modify receptor activity but also to exploit new chemical
      space for drug-like molecules. Such interactions may account for side-effects or
      undesirable properties associated with otherwise well-validated GPCR targets.
      Understanding and/or intervening in these interactions may allow scientists to
      progress those targets that may have been deemed unsuitable for therapeutic
      intervention. The present study reviews the opportunities for utilizing receptor
      interacting proteins as potential drug targets and the issues associated with
      them.

PMID- 15494042
TI  - Reproducibility of blood flow and post-occlusive reactive hyperaemia as measured
      by venous occlusion plethysmography.
AB  - Venous occlusion plethysmography is commonly used as a tool to assess BF (blood
      flow) and VR (vascular resistance) at baseline and during PORH (post-occlusive
      reactive hyperaemia). However, little is known about the reproducibility of this
      method. The purpose of the present study was to investigate short- (hours) and
      medium (week)-term reproducibility of forearm, calf and thigh BF and VR at
      baseline and during PORH. Reproducibility was assessed by the CV (coefficient of
      variation). In eight subjects, baseline BF and VR of the forearm, calf and thigh
      were measured using venous occlusion plethysmography (50 mmHg). PORH and minimal
      VR were measured after 13 min of arterial occlusion (220 mmHg). Reproducibility
      of baseline forearm and calf BF was acceptable and in agreement with previous
      studies (CV, 12.9-21.2%). Short- and medium-term reproducibility of thigh BF was
      good (CV, 5.9% and 8.7% respectively). Baseline VR showed acceptable-to-good
      reproducibility for forearm, calf and thigh (8.3-22.5%). Forearm PORH showed a CV
      of 6.1% (short term) and 8.6% (medium term); this was 6.1% (short term) and 6.4%
      (medium term) for the calf and 6.4% (short term) and 8.0% (medium term) for the
      thigh. Minimal VR showed good-to-acceptable reproducibility (CV, 6.1-11.7%). In
      conclusion, forearm, calf and thigh BF and PORH measured by plethysmography have
      an acceptable-to-good short- and medium-term reproducibility. Short- and medium
      term reproducibility of forearm and calf baseline BF are acceptable and thigh
      baseline BF has a good short- and medium-term reproducibility. Therefore
      plethysmography is a suitable low-cost tool to assess thigh baseline BF and PORH.

PMID- 15494043
TI  - Face-offs in reproductive immunology: the Montreal forum meeting report.
AB  - The combined 12th International Congress of Immunology (ICI) and the 4th Annual
      Conference of the Federation of Clinical Immunological Societies (FOCIS) was held
      in Montreal, Canada July 18-23, 2004 and attracted over 6000 immunologists and
      almost 4000 abstracts. The host society, the Canadian Society for Immunology
      (CSI) spent many years in preparation for this large meeting and encouraged its
      members to propose topics for symposia and mini-symposia and to sponsor satellite
      meetings. With sponsorship of CSI; the Canadian Institutes of Health Research;
      the University of Guelph, Guelph, ON; Queen's University, Kingston, ON; McGill
      University, Montreal, QU, Canada; and the American Society for Reproductive
      Immunology, a focused, highly successful, one day satellite meeting on human
      uterine immunology was held. The highlights of the presentations and discussions
      are reported.

PMID- 15494044
TI  - The effect of testosterone on cytokine production in the specific and non
      specific immune response.
AB  - PROBLEM: Cytokine production of monocytes and lymphocytes differs between males
      and females. This difference is characterized by a decreased percentage of
      interleukin (IL)-2-producing lymphocytes and an increased percentage of IL-12, IL
      1beta and tumour necrosis factor (TNF)-alpha-producing monocytes in males
      compared with females. In the present study, we investigated whether testosterone
      may explain these differences. METHOD OF STUDY: Stimulated whole blood of healthy
      woman was incubated with different concentrations of testosterone. Intracellular
      lymphocyte production of IL-2 and interferon (IFN)-gamma, as well as
      intracellular monocyte production of IL-12, IL-1beta and TNF-alpha were measured
      using flow cytometry. RESULTS: A significant increased percentage of IL-12- and
      IL-1beta-producing monocytes was found after incubation with physiological
      concentrations of testosterone. No effect of testosterone was found on IL-2- and
      IFN-gamma-producing lymphocytes and TNF-alpha-producing monocytes. CONCLUSIONS:
      The increased percentage of IL-12- and IL-1beta-producing monocytes in males
      compared with females in vivo may be induced by testosterone, as the in vitro
      percentage of IL-12- and IL-1beta-producing monocytes is increased after
      incubation with physiological concentrations of testosterone.

PMID- 15494045
TI  - The immune environment in human endometrium during the window of implantation.
AB  - PROBLEM: Changes in the immune environment in the endometrium are believed to be
      important for successful implantation and maintenance of pregnancy. We have
      previously investigated global gene profiling in human endometrium during the
      window of implantation by oligonucleotide microarray technology, and analysis of
      these data underscore the regulation of a group of immune-related genes. The
      present study was therefore conducted to examine the pattern of expression and
      regulation of these genes including decay accelerating factor (DAF), indoleamine
      2,3 dioxygenase (IDO), interleukin-15 (IL-15), IL-15 receptor alpha subunit (IL
      15Ralpha), interferon regulatory factor-1 (IRF-1), lymphotactin (Lpn), natural
      killer-associated transcript 2 (NKAT2) and NKG5 in secretory and proliferative
      human endometrium. METHOD OF STUDY: Endometrial biopsies were obtained from
      normally cycling women in the late proliferative and mid-secretory phase of the
      menstrual cycle. Semi-quantitative reverse transcriptase-polymerase chain
      reaction (RT-PCR) and Northern blot analysis were used to determine the
      expression and regulation of these genes in secretory and proliferative human
      endometrium. Cellular localization of NKG5, Lpn and IDO by in situ hybridization
      in secretory-phase endometrium was also examined. RESULTS: Semi-quantitative RT
      PCR and Northern blot results demonstrate that there is a coordinated
      upregulation of this group of genes during the window of implantation.
      CONCLUSIONS: We demonstrate the upregulation of immune-related genes IL-15Ralpha,
      Lpn and NKG5 in secretory versus proliferative human endometrium. We also
      demonstrate a similar upregulation in secretory endometrium of other immune
      related genes, viz, DAF, IDO, IL-15, IRF-1 and NKAT2. The functions of these
      genes include stimulation of proliferation of uterine natural killer (uNK) cells,
      inhibition of cytolytic activity of uNK cells, inhibition of cell growth of T
      cells and other pathogens and inhibition of the classical complement pathway.
      Upregulation of these immune-related genes in the window of implantation suggests
      their role during the process of implantation and in immune tolerance of the
      implanting conceptus.

PMID- 15494046
TI  - Effect of estradiol on mouse uterine epithelial cell transepithelial resistance
      (TER).
AB  - PROBLEM: The effects of estradiol on epithelial cell function in the uterus may
      either be direct or indirect through the paracrine effects of underlying stromal
      cells. The aim of this study was to test whether estradiol-17beta (E(2)) acts
      directly to regulate uterine epithelial cell monolayer integrity. METHODS OF
      STUDY: Mouse uterine epithelial cells were isolated and grown on cell culture
      inserts to form confluent, polarized monolayers, as indicated by the development
      of high transepithelial resistance (TER). RESULTS: When polarized epithelial
      cells were treated with E(2), TER was significantly decreased within 24 hr of
      exposure. Epithelial cells remained hormonally responsive in culture for at least
      10 days. In contrast to estradiol, incubation with progesterone, cortisol,
      aldosterone, and DHT had no effect on uterine epithelial cell TER. The ability of
      E(2) to decrease TER was inhibited following co-incubation with ICI 182,780, a
      pure estrogen receptor antagonist. To further investigate the mechanism involved
      in estradiol-induced decreases in TER, we tested the effect of TAPI-0, an
      inhibitor of matrix metalloproteinases. Our findings indicate that TAPI-0
      reversed the inhibitory effect of E(2) on TER. CONCLUSIONS: These studies
      demonstrate that epithelial monolayer integrity is directly influenced by E(2)
      and ER mediated. Further, it suggests that the mechanism through which estradiol
      decreases TER is mediated by matrix metalloproteinases.

PMID- 15494047
TI  - Anti-thyroid antibodies and antiphospholipid syndrome: evidence of reduced
      fecundity and of poor pregnancy outcome in recurrent spontaneous aborters.
AB  - PROBLEM: To determine the presence of anti-thyroid antibodies in patients with
      primary antiphospholipid syndrome (APS) [antiphospholipid antibodies (aPL) +
      recurrent spontaneous abortion (RSA)], compare APS alone with APS and thyroid
      autoimmunity for fecundity and for pregnancy outcome. METHOD OF STUDY: A total of
      203 non-pregnant women affected with primary APS were evaluated for anti-thyroid
      antibodies; 162 non-pregnant women affected with RSA and thyroid autoimmunity
      alone served as controls. RESULTS: Anti-thyroid antibodies were found in 27% of
      APS patients studied. Patients with aPL alone had higher percentages of
      spontaneous pregnancies (P < 0.0001) and live births (P = 0.0003), when compared
      with patients positive for anti-thyroid antibodies alone or with aPL.
      CONCLUSIONS: Thyroid autoimmunity is frequently present in APS recurrent aborters
      and is often associated with either reduced fecundity or with poor pregnancy
      outcome. Thyroid antibodies should always be evaluated in women with RSA
      including those with aPL.

PMID- 15494048
TI  - Increased numbers of activated mast cells in endometriosis lesions positive for
      corticotropin-releasing hormone and urocortin.
AB  - PROBLEM: Mast cells are critical in allergic and inflammatory diseases such as
      interstitial cystitis, which is often clinically associated with or mistaken as
      endometriosis. Mast cells had previously been reported to be increased at sites
      of endometriosis, and tryptase may contribute to the fibrosis and inflammation
      characterizing endometriosis. METHOD OF STUDY: This is a pilot study of mast cell
      numbers and its activation in endometriosis biopsies (n = 10) by immunostaining
      for mast cell tryptase, corticotropin-releasing hormone (CRH) and urocortin
      (Ucn). RESULTS: This is the first report that tryptase positive mast cells were
      not only increased (64-157 mast cells/mm(2)) in human endometriosis, but also
      highly activated (89%) in areas strongly stained positive for CRH/Ucn. Normal
      endometrium was weakly positive for both CRH/Ucn. CONCLUSION: High numbers of
      activated mast cells are present in endometriosis sites that were strongly
      positive for CRH/Ucn. CRH and Ucn may activate mast cells and contribute to the
      fibrosis and inflammation in endometriosis.

PMID- 15494049
TI  - Incidence and prevalence of toxoplasmosis in Indian pregnant women: a prospective
      study.
AB  - PROBLEM: Toxoplasmosis is a major cause of congenitally acquired infections
      causing high degree of morbidity and mortality in the newborns. METHODS OF STUDY:
      IgG avidity method was used to distinguish the recent and more than 4 months old
      infection in a prospective cohort study for the first time in India. One hundred
      and eighty pregnant women presented in their first 4 months of pregnancy were
      included in this study. Their sera were tested for anti-Toxoplasma gondii
      antibodies using direct agglutination test, immunoglobulin (Ig)G and IgM-enzyme
      linked immunosorbent assay, IgM-immunosorbent agglutination assay and VIDAS-IgG
      avidity. RESULTS: Overall IgG seroprevalence rate of toxoplasmosis was 45%. Only
      seven women (3.3%) were found to have IgM antibodies and only two of these showed
      low IgG avidity indicating recent infection of <or=4 months duration. One woman
      aborted spontaneously at her fourth month of gestation. In remaining five women
      the recent infection could successfully be excluded by IgG avidity testing. All
      these women had uneventful pregnancy. CONCLUSIONS: This study indicated that all
      IgM antibody positive pregnant must be tested for IgG avidity to rule out recent
      primary infection.

PMID- 15494050
TI  - The imbalanced mixed lymphocyte reaction between maternal and fetal lymphocytes
      as well as between the lymphocytes of adult children and their parents is
      mediated by activated CD8+ T cells.
AB  - PROBLEM: The mixed lymphocyte reaction (MLR) between maternal and fetal
      lymphocytes as well as between adult children and their parents is imbalanced in
      bidirectional mixed lymphocyte cultures. The present investigation was aimed at
      examining which type of T cells has primary responsibility for this phenomenon.
      METHODS: Two-way mixed lymphocyte cultures between lymphocytes of five female and
      five male adults and five male and five female newborns against lymphocytes of
      their parents were performed. Unrelated adults served as the controls. Before and
      after 72 hr incubation the mixed leukocytes cultures (MLCs) were sorted by flow
      cytometry according to the surface markers CD4 and CD69 or CD8 and CD69. The
      single cell populations within the four resulting fractions were discriminated by
      fluoresence in situ hybridization (FiSH) using xy-DNA probes. RESULTS: Before
      incubation the share of CD8(+) CD69(+) cells in the MLCs between mothers and
      their newborn infants was significantly shifted toward the newborn cells (P <
      0.01). After 72 hr incubation the CD8(+) CD69(+) ratio in the MLCs between mother
      and newborn cells and between adult children (male as well female) and their
      parents showed a significant shift of the CD8(+) CD69(+) cells toward the
      children's direction. All other MLCs showed a balanced cell population for all
      investigated cell types, both before and after incubation. CONCLUSION: The
      imbalanced MLR between maternal and fetal lymphocytes and lymphocytes of adult
      children against their parents is mediated by a specific imbalance of the
      activation of CD8(+) but not of CD4(+) T cells.

PMID- 15494051
TI  - Induction of systemic resistance to Pythium damping-off in cucumber plants by
      benzothiadiazole: ultrastructure and cytochemistry of the host response.
AB  - Benzo (1,2,3) thiadiazole-7-carbothioic acid S-methyl ester (BTH, CGA 245704), a
      non-toxic, synthetic chemical, was applied as a foliar spray to cucumber plants
      and evaluated for its potential to induce defense mechanisms in root tissues
      infected by the soilborne pathogen, Pythium ultimum Trow. In non-treated cucumber
      plants, fungal colonization was intense and paralleled marked host tissue damage,
      whereas in BTH-treated plants, pathogen ingress towards the vascular stele was
      apparently halted by the massive deposition of a phenolic-enriched material which
      occluded a large number of cortical and vascular parenchyma cells. This
      considerable increase in the accumulation of phenolics was accompanied by
      cytological disorders of the invading pathogen at a time when the wall-bound
      cellulose component was preserved. In addition to phenolic compounds, the
      occluding material contained large amounts of beta-glucoside residues. These
      residues gradually decreased in the areas neighboring fungal cells whereas
      phenolic deposition appeared to be more uniformly distributed throughout the
      occluded host cells. Pathogen penetration in non-occluded cucumber root cells
      coincided with other changes, mainly characterized by both the deposition onto
      the inner surface of the cell walls of some heterogeneous wall appositions and
      the coating of some intercellular spaces with an electron-opaque material.
      Evidence is provided in this study that BTH has the ability to induce SAR in
      cucumber. Exogenous, foliar applications of the chemical sensitize susceptible
      cucumber plants to react more rapidly and more efficiently to P. ultimum attack,
      mainly through the massive accumulation of phenolic compounds at sites of
      attempted pathogen penetration.

PMID- 15494052
TI  - Auxin transport inhibition precedes root nodule formation in white clover roots
      and is regulated by flavonoids and derivatives of chitin oligosaccharides.
AB  - The expression of the auxin responsive reporter construct, GH3:gusA, was examined
      in transgenic white clover plants to assess changes in the auxin balance during
      the earliest stages of root nodule formation. Reporter gene expression was
      monitored at marked locations after the application of bacteria or signal
      molecules using two precise inoculation techniques: spot-inoculation and a novel
      method for ballistic microtargeting. Changes in GH3:gusA expression were
      monitored after the inoculation of Rhizobium leguminosarum biovar trifolii, non
      host rhizobia, lipo-chitin oligosaccharides (LCOs), chitin oligosaccharides, a
      synthetic auxin transport inhibitor (naphthylphthalamic acid; NPA), auxin, the
      ENOD40-1 peptide or different flavonoids. The results show that clover-nodulating
      rhizobia induce a rapid, transient and local downregulation of GH3:gusA
      expression during nodule initiation followed by an upregulation of reporter gene
      expression at the site of nodule initiation. Microtargeting of auxin caused a
      local and acropetal upregulation of GH3:gusA expression, whereas NPA caused local
      and acropetal downregulation of expression. Both spot-inoculation and
      microtargeting of R. l. bv. trifolii LCOs or flavonoid aglycones induced similar
      changes to GH3:gusA expression as NPA. O-acetylated chitin oligosaccharides
      caused similar changes to GH3:gusA expression as R. l. bv. trifolii spot
      inoculation, but only after delivery by microtargeting. Non-O-acetylated chitin
      oligosaccharides, flavonoid glucosides or the ENOD40-1 peptide failed to induce
      any detectable changes in GH3:gusA expression. GH3:gusA expression patterns
      during the later stages of nodule and lateral root development were similar.
      These results support the hypothesis that LCOs and chitin oligosaccharides act by
      perturbing the auxin flow in the root during the earliest stages of nodule
      formation, and that endogenous flavonoids could mediate this response.

PMID- 15494053
TI  - Salicylic acid has a dual role in the activation of defence-related genes in
      parsley.
AB  - Systemic acquired resistance is an inducible plant defence state, the activation
      of which depends mostly on the accumulation of salicylic acid (SA). During the
      past several years, it has been demonstrated that pretreatment of cultured
      parsley cells with SA potentiates the elicitation of several defence responses
      that are local in whole plants, including the accumulation of phenylpropanoid
      products. Here it is reported that while anionic peroxidase and mannitol
      dehydrogenase encoding genes are directly responsive to SA, pretreating parsley
      cells with SA not only enhances elicitation of the phenylpropanoid genes
      phenylalanine ammonia-lyase and 4-coumarate:CoA ligase but also of genes for PR
      10 and a hydroxyproline-rich glycoprotein. Enhanced induction of these genes was
      seen at low levels of endogenous free SA. Enhancement of phenylalanine ammonia
      lyase gene activation was proportional to the length of SA pretreatment.
      Furthermore, the ability of SA analogues to both potentiate elicited and directly
      induce defence gene activation correlated with their biological activity to
      promote plant disease resistance. In summary, these results emphasize that SA has
      at least a dual role in plant defence gene activation.

PMID- 15494054
TI  - Effects of mevinolin on cell cycle progression and viability of tobacco BY-2
      cells.
AB  - Mevinolin, an inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, was used to
      study the importance of mevalonic acid (MVA) for cell cycle progression of
      tobacco (Nicotiana tabacum L.) BY-2 cells. After treatment with 5 microM
      mevinolin, the cell cycle progression was completely blocked and two cell
      populations accumulated (80% in phase G0/G1 and 20% in G2/M). The arrest could be
      released by subsequent addition of MVA. Effects were compared to those caused by
      aphidicolin, an inhibitor of alpha-like DNA polymerases that blocks cell cycle at
      the entry of the S phase. The 80% proportion of mevinolin-treated TBY-2 cells was
      clearly arrested before the aphidicolin-inducible block. By the aid of a double
      blocking technique, it was shown that the mevinolin-induced cell arrest of highly
      synchronized cells was due to interaction with a control point located at the
      mitotic telophase/entry G1 phase. Depending on the developmental stage, mevinolin
      induced rapid cell death in a considerable percentage of cells. Mevinolin
      treatment led to a partial synchronization, as shown by the increase in mitotic
      index. The following decrease was correlated with the above-mentioned induction
      of cell death.

PMID- 15494055
TI  - The characterization of gio, a new pea mutant, shows the role of indoleacetic
      acid in the control of fruit development by the apical shoot.
AB  - Fruit-set and fruit growth in pea (Pisum sativum L.) depend on gibberellins
      (GAs). The authors have isolated a new pea mutant, gio, which appeared
      spontaneously within the population of the cultivar Alaska, characterized by
      unpollinated ovaries much less sensitive to applied GAs. The mutant also has
      elongated peduncles, and is taller than the wild-type (WT) because the upper
      plant internodes are longer. Contrary to WT, the gio ovaries respond very little
      to benzylaminopurine (BAP) and 2,4-dichlorophenoxyacetic acid, but become fully
      sensitive to GA(3) when this hormone is applied together with BAP. The gio
      phenotype is determined by a mutation at a single mendelian locus. The mutation
      is recesive, shows incomplete penetrance, and its expression depends on
      environmental culture conditions. The sensitivity of the ovaries to GA(3) can be
      recovered by removing the apical shoot (plant decapitation) and by blocking the
      transport of indoleacetic acid (IAA) from the apical shoot with 2,3,5
      triiodobenzoic acid. The content of IAA in methanolic extracts and phloematic
      exudates of the apical shoot of gio is about double that in the WT. The rate of
      transport of [(3)H]IAA applied to the apex of the mutant is also twice that in
      the WT. This indicates that the insensitivity of the gio ovaries to GAs is due to
      the inhibitory effect of the higher basipetal IAA transport from the shoot. The
      interaction between the fruit and the apical shoot mediated by IAA probably also
      involves cytokinins transported from the basal part of the plant.

PMID- 15494056
TI  - Gene silencing from plant DNA carried by a Geminivirus.
AB  - The geminivirus tomato golden mosaic virus (TGMV) replicates in nuclei and
      expresses genes from high copy number DNA episomes. The authors used TGMV as a
      vector to determine whether episomal DNA can cause silencing of homologous,
      chromosomal genes. Two markers were used to asses silencing: (1) the sulfur
      allele (su) of magnesium chelatase, an enzyme required for chlorophyll formation;
      and (2) the firefly luciferase gene (luc). Various portions of both marker genes
      were inserted into TGMV in place of the coat protein open-reading frame and the
      constructs were introduced into intact plants using particle bombardment. When
      TGMV vectors carrying fragments of su (TGMV::su) were introduced into leaves of
      wild type Nicotiana benthamiana, circular, yellow spots with an area of several
      hundred cells formed after 3-5 days. Systemic movement of TGMV::su subsequently
      produced varigated leaf and stem tissue. Fragments that caused silencing included
      a 786 bp 5' fragment of the 1392 bp su cDNA in sense and anti-sense orientation,
      and a 403 bp 3' fragment. TGMV::su-induced silencing was propogated through
      tissue culture, along with the viral episome, but was not retained through
      meiosis. Systemic downregulation of a constitutively expresse luciferase
      transgene in plants was achieved following infection with TGMV vectors carrying a
      623 bp portion of luc in sense or anti-sense orientation. These results establish
      that homologous DNA sequences localized in nuclear episomes can modulate the
      expression of active chromosomal genes.

PMID- 15494057
TI  - Regulation of Rubisco activation in antisense plants of tobacco containing
      reduced levels of Rubisco activase.
AB  - Following an increase in photon flux density (PFD), ribulose bisphosphate
      carboxylase/oxygenase (Rubisco) undergoes a slow activation which substantially
      limits the rate of photosynthesis. This activation process is mediated in part by
      Rubisco activase. Antisense DNA plants of tobacco were used to quantify the
      degree to which activase limits Rubisco activation. Reductions in leaf activase
      content caused proportional reductions in the rate of Rubisco activation
      following a PFD increase from 110 to 1200 micromol m(-2) sec(-1). This was the
      case for activase levels up to and slightly beyond normal wild-type activase
      levels. Activase therefore has a flux control coefficient of unity with respect
      to the Rubisco activation flux. Such a high control coefficient has rarely been
      measured for any metabolic system, and this is the highest control coefficient
      measured for an important photosynthetic flux. In contrast, the rate of Rubisco
      inactivation in leaves following a drop in PFD of 1200 to 110 micromol m(-2) sec(
      1) was unchanged by a 60% reduction in activase levels. Despite the high degree
      of control that activase exerts over the rate of activation, and thus non-steady
      state photosynthesis, it was shown that steady-state photosynthesis was largely
      unaffected by activase concentration until it was reduced below approximately 15%
      of the wild-type level. The significance of these results and their implications
      for published models of Rubisco activation are discussed.

PMID- 15494058
TI  - Recurrent onset of epigenetic silencing in rice harboring a multi-copy transgene.
AB  - Extensive methylation of the Ubi1 promoter has been shown to be associated with
      transcriptional silencing and bialaphos herbicide sensitivity in several R(1)
      progeny derived from a transgenic rice line, JKA 52, containing multiple copies
      of the introduced genes (Kumpatla et al. 1997;Plant Physiol. 115, 361-373). All
      of the progeny from silenced R(1) lines were silenced, and a proportion (24%) of
      the R(2) seedlings from JKA 52-6, a non-silenced homozygous R(1) line, were found
      to be silenced. Several non-silenced (bialaphos-resistant) R(2) progeny derived
      from the selfed seed of JKA 52-6 were tested at various stages throughout the
      growth period and found to be resistant to bialaphos, indicating the absence of
      silencing. Five of these were investigated further to determine whether silencing
      could recur in subsequent generations. R(3) seedlings were raised from selfed
      R(2) seed and herbicide sensitivity was detected in 5-40% of the plants in three
      of the five lines. This silencing was accompanied by methylation of the Ubi1
      promoter and the absence of steady-state bar mRNA. This recurrent onset of
      silencing and instability of expression associated with a transgene locus
      containing several repeated sequences is undesirable. The data strongly suggest
      that multi-generation molecular analysis should be undertaken for transgenic
      lines to be used for agricultural purposes and that lines containing methylated
      inserts should be carefully evaluated before being included in further breeding
      strategies.

PMID- 15494059
TI  - A novel tomato gene that rapidly responds to wound- and pathogen-related signals.
AB  - The expression of a novel defence-related gene from tomato which responds rapidly
      to wound- and pathogen-related signals has been characterised. The gene, which
      encodes a protein with homology to glucosyl transferase enzymes, is expressed
      within 15 min of mechanical damage to tomato leaves, and responds to signals
      which differ from those on the systemin/jasmonic acid pathway typical of well
      characterised wound-induced genes of tomato. Furthermore, expression of the gene
      is also rapidly and specifically induced during a resistance response elicited by
      the application of Avr9 avirulence peptide to tomato plants carrying the
      corresponding Cf9 resistance gene. Whilst expression can also be induced by the
      application of exogenous salicylic acid and related analogues to tomato plants,
      several lines of evidence suggest that elevated salicylic acid is not a causal
      signal in planta during either the wound or pathogen resistance response.

PMID- 15494060
TI  - Obstacles in large-scale epidemiological assessment of sensory impairments in a
      Dutch population with intellectual disabilities.
AB  - BACKGROUND: A population-based epidemiological study on visual and hearing
      impairment was planned in a random sample of 2100 clients, drawn from a base
      population of 9012 users of Dutch residential and day-care intellectual
      disability (ID) services with the whole range of IDs. Stratification was applied
      for age 50 years and over and Down syndrome. Visual and hearing functions were
      assessed according to a standardized protocol, in cooperation with regular
      ophthalmologists and regional audiological centres. Anticipated obstacles in
      sample collection, random inclusion, informed consent, expertise of
      investigators, time and costs were eliminated by a careful preparation. However,
      inclusion and participation were incomplete. METHOD: In a descriptive
      retrospective design, we collected data from our study files on inclusion and
      participation as well as reasons for non-participation, to identify unanticipated
      obstacles for this kind of research. RESULTS: Consent was obtained for 1660
      clients, and 1598 clients participated in the data collection (76% of intended
      sample of 2100). Inclusion and participation rates were especially lower in
      community-based care organizations, resulting in unintentional skewing of the
      sample towards more severe levels of ID. Complete and reliable data to diagnose
      visual impairment were obtained for 1358/1598 (85%) and to diagnose hearing
      impairment for 1237/1598 participants (77%). Unanticipated obstacles had to do
      with the quality of coordination within care organizations, with characteristics
      of screening methods, and with collaboration with the regular health care system.
      Assessments of visual function were more easy to organize than were those of
      hearing. Based on our current experience, practical recommendations are given for
      future multicentre research, especially in community-based settings.

PMID- 15494061
TI  - Coping with social stigma: people with intellectual disabilities moving from
      institutions and family home.
AB  - BACKGROUND: Social stigma and its impact on the life opportunities and emotional
      well-being of people with intellectual disabilities (IDs) are a subject of both
      practical and theoretical importance. The disability movement and evolving
      theories of self, now point to individuals' ability to develop positive
      identities and to challenge stigmatizing views and social norms. METHOD: This
      paper presents findings from a phenomenological study of 10 individuals making
      the transition from their family home to live more independently and 18
      individuals moving from a long-stay hospital to live in community housing. It
      builds on an earlier data set obtained from people living at home with their
      families and examines: (1) people's awareness of stigma, and (2) their modes of
      adaptation to stigma. RESULTS: The participants all believed that they faced
      stigmatized treatment and were aware of the stigma associated with ID. They
      presented a range of views about self in relation to disability and stigma. These
      views included regarding themselves as part of a minority group who reject
      prejudice, and attempts to distance themselves from stigmatizing services and
      from other individuals with IDs. CONCLUSIONS: The findings are discussed in
      relation to theories of self and the importance of considering psychosocial
      factors is stressed in clinical work with people who have IDs.

PMID- 15494062
TI  - Improving functional skills and physical fitness in children with Rett syndrome.
AB  - BACKGROUND: To investigate the feasibility of a physical exercise programme with
      treadmill for persons with Rett syndrome (RS) in order to promote fitness and
      health. METHODS: A daily training programme on a treadmill was designed for four
      females with RS over a period of 2 months with tests performed in three
      intervals, at time 1, 2 and 3, 2 months apart with intervention taking place
      between tests 2 and 3. Participants were four girls with RS aged 8.5-11 years
      (mean: 10 years) attending the educational facility Beit Issie Shapiro, Raanana,
      Israel, all with independent mobility and with typical characteristics of RS
      stage III. The training took place at the educational facility, on a 1400 model
      treadmill (Trimline, capable of very low speeds < 0.5 k/h), with very long side
      rails. Special low side rails were adapted to the treadmill in order to fit the
      height of the children and velcro straps were added to assist in safely placing
      the hands. Pulse was monitored constantly during exercise by an A3 polar pulse
      belt. Pulse measurements at rest during training were considered as evaluators of
      aerobic physical condition. Functional measurement was based on a scale specially
      established for the present study. The scale was a 31-item motor-functioning tool
      that measures the ability of participants to knee walk and knee stand, to get up
      to a standing position, duration of walking different paths, and to go up and
      down stairs and slopes. RESULTS: The study showed that physical fitness of the
      children at the end of the training programme had improved considerably (P <
      0.05). Tests showed that general functional abilities had improved considerably
      (P < 0.0001). Although all items of the functional ability measure showed
      impressive positive change, some of the 31 items on it showed statistically
      significant improvement (knee walking, going up and down stairs and speed of
      walking for 25 m. Pearson correlation showed high linkage (r = -0.76) between
      functional improvement and change in physical fitness. CONCLUSIONS: Physical
      fitness programme executed on a daily basis is capable of improving functional
      ability of children with RS. Nonprofessional personnel can execute such a
      programme under supervision of a qualified physical therapist.

PMID- 15494063
TI  - Vision in athletes with intellectual disabilities: the need for improved eyecare.
AB  - BACKGROUND: Special Olympics provides sporting opportunities for people with
      intellectual disabilities (ID), and Lions Clubs International Opening Eyes GB
      offers vision screening for athletes at Special Olympics Games. METHODS: Opening
      Eyes GB screened the vision of 505 UK athletes at its inaugural event in 2001.
      The results were analysed and are presented here. RESULTS: Results showed that
      athletes do not differ from other people with ID in being at high risk of ocular
      and visual defects and many are not accessing eyecare. 15% reported never having
      an optometric eye examination, and yet 19% of these athletes had a significant
      refractive error, 32% had ocular anomalies and 6% were visually impaired.
      Overall, findings confirmed the high prevalence of refractive errors and
      strabismus amongst people with ID. 40% of athletes had ocular abnormalities,
      including 15.6% with blepharitis, a readily treatable condition that causes
      discomfort. 9% had lens opacities, of which half were probably impairing sight.
      An important finding was that many athletes have reduced vision and 14% could be
      classified as visually impaired (WHO definition) even when refractive errors were
      fully corrected. CONCLUSIONS: Special Olympics athletes should be encouraged to
      have regular eye examinations (as indeed, should all people with ID), and
      educators, carers and coaches need appropriate information about the visual
      status of their charges.

PMID- 15494064
TI  - Consistent mapping and automatic visual search: comparing persons with and
      without intellectual disability.
AB  - BACKGROUND: Merrill et al. (1996) reported that persons with intellectual
      disability (ID) were slower at learning a visual search task to automaticity
      relative to persons of the same age without ID. For persons without ID,
      automaticity develops most rapidly under conditions in which a response is always
      the same for a particular stimulus. This study was designed to investigate
      whether persons with and without ID are differentially sensitive to the influence
      of consistently mapped versus inconsistently mapped stimulus responses. METHODS:
      The primary manipulation was the consistency between a particular stimulus and
      the response to that stimulus in a visual search task. Sixteen participants with
      ID and 16 without ID searched displays of two, three, or four pictured objects to
      determine if a target was present. For half of the participants, the targets were
      always targets. For the other half, the targets became nontargets on 25% of the
      trials. RESULTS: Analyses focused on changes in response times associated with
      set size. Because automaticity allows for parallel processing, the elimination of
      significant effects of set size was taken as an index of the development of
      automaticity. Results indicated that inconsistent mapping significantly slowed
      the development of automaticity for the participants without ID but not for the
      participants with ID. DISCUSSION: Results were discussed in terms of the role of
      inhibition processes in the development of automatic search and detection. The
      effectiveness of inhibition processes was compromised by the consistency
      manipulation. The effect of the consistency manipulation was greater for the
      participants without ID because they were presumed to be using inhibition
      processes more effectively during practice than did the participants with ID.

PMID- 15494066
TI  - Intravenous sedation for dental patients with intellectual disability.
AB  - BACKGROUND: The poor quality of oral health care for people with intellectual
      disability (ID) has been recognized, and the strong fears about dental treatment
      suggested as a major reason for disturbances of visits to dentists by such
      patients. Intravenous sedation is a useful method for relieving the anxiety and
      fear of such patients about dental treatment, and is frequently essential for ID
      patients undergoing dental treatment. However, decision regarding the dose of
      sedative required to be administered for an adequate level of sedation is
      difficult because the effect of sedation cannot be adequately assessed in
      patients with severe ID. As an appropriate sedative dose for dental patients with
      ID has not been fully established, we investigated sedative doses required and
      the effect of sedation in patients with ID, compared with other dental patients.
      METHODS: We reviewed the anaesthetic records of dental patients with ID (73
      cases) and other dental patients (19 cases) aged between 20 and 29 years who had
      undergone intravenous sedation with midazolam and propofol in Okayama University
      Dental Hospital, from January 2000 to December 2000. Intravenous sedation was
      induced with a bolus intravenous administration of midazolam (2-3 mg) and
      maintained with a continuous infusion of propofol. The dose of propofol was
      titrated to achieve an adequate level of sedation: asleep but responding to
      painful stimulation. The efficacy of sedation, the required doses of propofol,
      and the wake-up times were investigated for all subjects. The efficacy of
      sedation was evaluated by judging whether the patient became cooperative and
      allowed the dental treatment to be carried out or not. The complications induced
      by intravenous sedation were also evaluated in each subject. Differences in
      variables between subjects with ID and other subjects were analysed using the
      Mann-Whitney U-test. RESULTS: Intravenous sedation was effective for dental
      treatment in all subjects with or without ID. The required dose of propofol in
      subjects with ID was 4.74 mg/kg/h (2.63-10.33 mg/kg/h), significantly higher than
      that required for other subjects (3.31, 1.72-4.80 mg/kg/h). Wake-up times of
      subjects with ID were similar to those of the other subjects. Severe
      complications were not seen during or after intravenous sedation. CONCLUSION: The
      results of this study show that intravenous sedation is a useful method for
      dental patients with ID as well as for other dental patients, but indicate that
      dental patients with ID need higher doses of sedative to obtain an adequate level
      of sedation.

PMID- 15494065
TI  - Attitude to medication of parents/primary carers of people with intellectual
      disability.
AB  - OBJECTIVE: To investigate the influence of attitudes of carers of people with
      intellectual disability (ID) towards giving medication. METHOD: Ninety-three
      carers of service users who are currently attending outpatients clinic (Harrow
      Learning Disability service) were interviewed, using the RAMS (Rating of Attitude
      to Medication Scale) interview schedule. RESULTS: A significant association was
      found between relationship of the carer to the service user and overall positive
      or negative attitude towards medication, with a disproportionate number of
      parents expressing a negative attitude in comparison with professional carers
      (46% vs. 11%). CONCLUSION: This study suggests more work needs to be done with
      family carers than with professional carers to improve compliance with
      medication. Stigma is still associated with ID and psychiatric disorders. The
      family carers responses may be projecting their feelings related to the impact of
      having a child not only with ID, but also with additional psychiatric problems.
      The implication of the study for psychiatrists is the identification of a number
      of areas that could be usefully explored before writing a prescription.

PMID- 15494067
TI  - Magnetic resonance imaging in people with Down's syndrome and Alzheimer's
      disease.

PMID- 15494069
TI  - First successful case of in vitro fertilization-embryo transfer with venom
      immunotherapy for hymenoptera sting allergy.
AB  - BACKGROUND: To describe immune and endocrine responses in severe hymenoptera
      hypersensitivity requiring venom immunotherapy (VIT) during in vitro
      fertilization (IVF). CASE PRESENTATION: A 39-year old patient was referred for
      history of multiple miscarriage and a history of insect sting allergy. Four years
      earlier, she began subcutaneous injection of 100 mcg mixed vespid hymenoptera
      venom/venom protein every 5-6 weeks. The patient had one livebirth and three
      first trimester miscarriages. Allergy treatment was maintained for all
      pregnancies ending in miscarriage, although allergy therapy was discontinued for
      the pregnancy that resulted in delivery. At our institution ovulation induction
      incorporated venom immunotherapy (VIT) during IVF, with a reduced VIT dose when
      pregnancy was first identified. Serum IgE was monitored with estradiol during
      ovulation induction and early pregnancy. Response to controlled ovarian
      hyperstimulation was favorable while VIT was continued, with retrieval of 12
      oocytes. Serum RAST (yellow jacket) IgE levels fluctuated in a nonlinear fashion
      (range 36-54%) during gonadotropin therapy and declined after hCG administration.
      A healthy female infant was delivered at 35 weeks gestation. The patient
      experienced no untoward effects from any medications during therapy. CONCLUSION:
      Our case confirms the safety of VIT in pregnancy, and demonstrates RAST IgE can
      remain <60% during IVF. With proper monitoring, VIT during IVF can be safe and
      appropriate for selected patients and does not appear to adversely affect
      blastocyst implantation, early embryo development or perinatal outcome. Further
      studies will be needed to develop VIT guidelines specifically applicable to IVF.

PMID- 15494070
TI  - Perivascular epithelioid cell tumor (PEComa) of the uterine cervix associated
      with intraabdominal "PEComatosis": A clinicopathological study with comparative
      genomic hybridization analysis.
AB  - BACKGROUND: The World Health Organization recently recognized a family of
      neoplasms showing at least partial morphological or immunohistochemical evidence
      of a putative perivascular epithelioid cell (PEC) differentiation. These tumors
      include angiomyolipoma (AML), clear cell "sugar" tumors of the lung (CCST),
      lymphangioleiomyomatosis (LAM), clear cell myomelanocytic tumors of the falciform
      ligament and distinctive clear cell tumors at various other anatomic sites. CASE
      PRESENTATION & METHODS: A 41-year old gravida-1 para-1 with tuberous sclerosis
      presented with an incidentally identified 2.2 cm mass. The morphology and
      immunohistochemical profile was consistent with PEComa. Distinct aggregates of
      HMB-45 epithelioid cells were present in an occasionally distinctive perivascular
      distribution in the myometrium, small bowel lamina propria and ovarian hila.
      These distinctive aggregates, for which we propose the designation "PEComatosis"
      based on their intraabdominal distribution, did not display cytological atypia,
      mitotic activity or necrosis. CGH and DNA ploidy analysis showed a balanced
      chromosomal profile and diploid nuclei, respectively. There was no recurrence or
      metastases at 35 months' follow-up. Fifty-one previously reported cases of non
      AML, LAM and CCST PEComas [perivascular epithelioid cell tumors- not otherwise
      specified (PEComa-NOS)] are reviewed. CONCLUSIONS: The lesions may be a
      reflection of tumor multicentricity, in which each may be a potential nidus for
      the development of future more well-developed tumors. Alternatively, they may be
      a manifestation of a poorly understood "field effect", in which there is an
      increased propensity to develop tumors of this type throughout the abdomen.
      Finally, and least likely in our opinion, they may represent tumor spread from
      its primary site.

PMID- 15494071
TI  - Modeling of cell signaling pathways in macrophages by semantic networks.
AB  - BACKGROUND: Substantial amounts of data on cell signaling, metabolic, gene
      regulatory and other biological pathways have been accumulated in literature and
      electronic databases. Conventionally, this information is stored in the form of
      pathway diagrams and can be characterized as highly "compartmental" (i.e.
      individual pathways are not connected into more general networks). Current
      approaches for representing pathways are limited in their capacity to model
      molecular interactions in their spatial and temporal context. Moreover, the
      critical knowledge of cause-effect relationships among signaling events is not
      reflected by most conventional approaches for manipulating pathways. RESULTS: We
      have applied a semantic network (SN) approach to develop and implement a model
      for cell signaling pathways. The semantic model has mapped biological concepts to
      a set of semantic agents and relationships, and characterized cell signaling
      events and their participants in the hierarchical and spatial context. In
      particular, the available information on the behaviors and interactions of the
      PI3K enzyme family has been integrated into the SN environment and a cell
      signaling network in human macrophages has been constructed. A SN-application has
      been developed to manipulate the locations and the states of molecules and to
      observe their actions under different biological scenarios. The approach allowed
      qualitative simulation of cell signaling events involving PI3Ks and identified
      pathways of molecular interactions that led to known cellular responses as well
      as other potential responses during bacterial invasions in macrophages.
      CONCLUSIONS: We concluded from our results that the semantic network is an
      effective method to model cell signaling pathways. The semantic model allows
      proper representation and integration of information on biological structures and
      their interactions at different levels. The reconstruction of the cell signaling
      network in the macrophage allowed detailed investigation of connections among
      various essential molecules and reflected the cause-effect relationships among
      signaling events. The simulation demonstrated the dynamics of the semantic
      network, where a change of states on a molecule can alter its function and
      potentially cause a chain-reaction effect in the system.

PMID- 15494072
TI  - Image fusion for dynamic contrast enhanced magnetic resonance imaging.
AB  - BACKGROUND: Multivariate imaging techniques such as dynamic contrast-enhanced
      magnetic resonance imaging (DCE-MRI) have been shown to provide valuable
      information for medical diagnosis. Even though these techniques provide new
      information, integrating and evaluating the much wider range of information is a
      challenging task for the human observer. This task may be assisted with the use
      of image fusion algorithms. METHODS: In this paper, image fusion based on Kernel
      Principal Component Analysis (KPCA) is proposed for the first time. It is
      demonstrated that a priori knowledge about the data domain can be easily
      incorporated into the parametrisation of the KPCA, leading to task-oriented
      visualisations of the multivariate data. The results of the fusion process are
      compared with those of the well-known and established standard linear Principal
      Component Analysis (PCA) by means of temporal sequences of 3D MRI volumes from
      six patients who took part in a breast cancer screening study. RESULTS: The PCA
      and KPCA algorithms are able to integrate information from a sequence of MRI
      volumes into informative gray value or colour images. By incorporating a priori
      knowledge, the fusion process can be automated and optimised in order to
      visualise suspicious lesions with high contrast to normal tissue. CONCLUSION: Our
      machine learning based image fusion approach maps the full signal space of a
      temporal DCE-MRI sequence to a single meaningful visualisation with good
      tissue/lesion contrast and thus supports the radiologist during manual image
      evaluation.

PMID- 15494073
TI  - Molecular mechanisms of heptaplatin effective against cisplatin-resistant cancer
      cell lines: less involvement of metallothionein.
AB  - BACKGROUND: Heptaplatin is a new platinum derivative with anticancer activity
      against various cancer cell lines, including cisplatin-resistant cancer cell
      lines (Cancer Chemother Pharmacol 1995; 35: 441). METHODS: Molecular mechanisms
      of heptaplatin effective against cisplatin-resistant cancer cell lines has been
      investigated in connection with metallothionein (MT). Cytotoxicity was determined
      by an MTT assay. MT mRNA, was determined by RT-PCR assay. Transfection study was
      carried out to examine the function of MT. RESULTS: Of various gastric cancer
      cell lines, SNU-638 and SNU-601 showed the highest and lowest levels of MT mRNA,
      respectively, showing 80-fold difference. The IC50 values of SNU-638 to
      cisplatin, carboplatin and heptaplatin were 11.2-fold, 5.1-fold and 2.0-fold
      greater than those of SNU-601, respectively. Heptaplatin was more effective
      against cisplatin-resistant and MT-transfected gastric cancer sublines than
      cisplatin or carboplatin was. In addition, heptaplatin attenuated cadmium, but
      not zinc, induction of MT. CONCLUSION: These results indicate that molecular
      mechanisms of heptaplatin effective against cisplatin-resistant gastric cancer
      sublines is at least in part due to the less involvement of MT in heptaplatin
      resistance as well as its attenuation of MT induction.

PMID- 15494074
TI  - Tracheal adenoid cystic carcinoma masquerading asthma: a case report.
AB  - BACKGROUND: Tracheal tumors are often misdiagnosed as asthma and are treated with
      inhaled steroids and bronchodilators without resolution. CASE PRESENTATION: Here,
      a patient with tracheal adenoid cystic carcinoma who had been previously
      diagnosed with difficult asthma was reported. The possibility of the presence of
      localized airway obstruction was raised when the flow-volume curve suggesting
      fixed airway obstruction, was obtained. CONCLUSION: The presenting case report
      emphasizes the fact that not all wheezes are asthma. It is critical to bear in
      mind that if a patient does not respond to appropriate anti-asthma therapy,
      localized obstructions should be ruled out before establishing the diagnosis of
      asthma.

PMID- 15494075
TI  - Rupture of totally implantable central venous access devices (Intraports) in
      patients with cancer: report of four cases.
AB  - BACKGROUND: Totally implantable central venous access devices (intraports) are
      commonly used in cancer patients to administer chemotherapy or parenteral
      nutrition. Rupture of intraport is a rare complication. PATIENTS AND METHODS:
      During 3 years period, a total of 245 intraports were placed in cancer patients
      for chemotherapy. Four of these cases (two colon cancer and one each of pancreas
      and breast cancer) had rupture of the intraport catheter, these forms the basis
      of present report. RESULTS: Mean time insitu for intraports was 164 (35) days.
      Median follow-up time was 290 days and total port time in situ was 40180 days.
      The incidence of port rupture was 1 per 10,000 port days. Three of the 4 cases
      were managed by successful removal of catheters. In two of these the catheter was
      removed under fluoroscopic control using femoral route, while in the third
      patient the catheter (partial rupture) was removed surgically. One of the
      catheters could not be removed and migrated to right ventricle on manipulations.
      CONCLUSION: Port catheter rupture is a rare but dreaded complication associated
      with subcutaneous port catheter device placement for chemotherapy. In case of
      such an event the patient should be managed by an experienced vascular surgeon
      and interventional radiologist, as in most cases the ruptured catheter can be
      retrieved by non operative interventional measures.

PMID- 15494076
TI  - The connection domain in reverse transcriptase facilitates the in vivo annealing
      of tRNALys3 to HIV-1 genomic RNA.
AB  - The primer tRNA for reverse transcription in HIV-1, tRNALys3, is selectively
      packaged into the virus during its assembly, and annealed to the viral genomic
      RNA. The ribonucleoprotein complex that is involved in the packaging and
      annealing of tRNALys into HIV-1 consists of Gag, GagPol, tRNALys, lysyl-tRNA
      synthetase (LysRS), and viral genomic RNA. Gag targets tRNALys for viral
      packaging through Gag's interaction with LysRS, a tRNALys-binding protein, while
      reverse transcriptase (RT) sequences within GagPol (the thumb domain) bind to
      tRNALys. The further annealing of tRNALys3 to viral RNA requires nucleocapsid
      (NC) sequences in Gag, but not the NC sequences GagPol. In this report, we
      further show that while the RT connection domain in GagPol is not required for
      tRNALys3 packaging into the virus, it is required for tRNALys3 annealing to the
      viral RNA genome.

PMID- 15494077
TI  - Musculo-skeletal pain among 40- and 45-year olds in Oslo: differences between two
      socioeconomically contrasting areas, and their possible explanations.
AB  - BACKGROUND: The objective of the study was to compare the prevalence and severity
      of musculo-skeletal pain between two socioeconomically contrasting areas in Oslo,
      Norway, and to explore possible explanatory factors. METHODS: Questionnaire
      survey, carried out as part of The Oslo Health Study in 2000-2001. Data from 821
      persons (40 and 45 year old) living in a less affluent inner city area (called
      east) were compared with 854 persons living in an affluent area of the city
      (called west). Bivariate comparisons (chi square test) and multiple regression
      analyses were performed to investigate differences between the samples. RESULTS:
      61 % in east and 56 % in west (p < 0.05) reported pain/stiffness in
      muscles/joints during the last four weeks. 30 % in east versus 19 % in west (p <
      0.001) reported extensive pain. The between area difference in extensive pain was
      partially explained by physical inactivity, mental health problems and being of
      non-Western origin. CONCLUSION: Musculo-skeletal pain is reported by 55-60 % of
      middle aged persons in Oslo during a four week period, and must be considered a
      normal phenomenon. Poor social conditions, inactivity, mental health problems and
      being an immigrant imply increased risk of more severe symptoms with a
      concomitant demand of health care.

PMID- 15494078
TI  - PASBio: predicate-argument structures for event extraction in molecular biology.
AB  - BACKGROUND: The exploitation of information extraction (IE), a technology aiming
      to provide instances of structured representations from free-form text, has been
      rapidly growing within the molecular biology (MB) research community to keep
      track of the latest results reported in literature. IE systems have traditionally
      used shallow syntactic patterns for matching facts in sentences but such
      approaches appear inadequate to achieve high accuracy in MB event extraction due
      to complex sentence structure. A consensus in the IE community is emerging on the
      necessity for exploiting deeper knowledge structures such as through the
      relations between a verb and its arguments shown by predicate-argument structure
      (PAS). PAS is of interest as structures typically correspond to events of
      interest and their participating entities. For this to be realized within IE a
      key knowledge component is the definition of PAS frames. PAS frames for non
      technical domains such as newswire are already being constructed in several
      projects such as PropBank, VerbNet, and FrameNet. Knowledge from PAS should
      enable more accurate applications in several areas where sentence understanding
      is required like machine translation and text summarization. In this article, we
      explore the need to adapt PAS for the MB domain and specify PAS frames to support
      IE, as well as outlining the major issues that require consideration in their
      construction. RESULTS: We introduce PASBio by extending a model based on PropBank
      to the MB domain. The hypothesis we explore is that PAS holds the key for
      understanding relationships describing the roles of genes and gene products in
      mediating their biological functions. We chose predicates describing gene
      expression, molecular interactions and signal transduction events with the aim of
      covering a number of research areas in MB. Analysis was performed on sentences
      containing a set of verbal predicates from MEDLINE and full text journals.
      Results confirm the necessity to analyze PAS specifically for MB domain.
      CONCLUSIONS: At present PASBio contains the analyzed PAS of over 30 verbs,
      publicly available on the Internet for use in advanced applications. In the
      future we aim to expand the knowledge base to cover more verbs and the nominal
      form of each predicate.

PMID- 15494079
TI  - Reduced inhibitory action of a GABAB receptor agonist on [3H]-dopamine release
      from rat ventral tegmental area in vitro after chronic nicotine administration.
AB  - BACKGROUND: The activation of GABAB receptors in the ventral tegmental area (VTA)
      has been suggested to attenuate the rewarding properties of psychostimulants,
      including nicotine. However, the neurochemical mechanism that underlie this
      effect remains unknown. Since GABAB receptors modulate the release of several
      neurotransmitters in the mammalian brain, we have characterised the effect of the
      GABAB receptor agonist baclofen on the release of [3H]-dopamine ([3H]-DA) from
      VTA slices of naive rats and of rats pre-treated with nicotine. RESULTS: In naive
      rats, baclofen concentration-dependently inhibited the electrically evoked
      release of [3H]-DA from the isolated VTA (EC50 = 0.103 microM, 95% CI = 0.043
      0.249), without affecting the basal [3H]-monoamine overflow. This effect was
      mediated by activation of GABAB receptors as it was blocked by the selective
      receptor antagonist CGP55845A. Chronic administration of nicotine (0.4 mg kg(-1),
      s.c., for 14 days) affected neither the basal nor the electrically evoked release
      of [3H]-DA from VTA slices. However, the inhibitory effect of baclofen (10
      microM) on the stimulated [3H]-monoamine overflow was abolished in rats pre
      treated with nicotine as compared to saline-injected controls. CONCLUSIONS: Our
      results demonstrate that GABAB receptor activation reduces the release of DA from
      the rat VTA. In addition, a reduced sensitivity of VTA GABAB receptors appears to
      develop after chronic exposure to nicotine. The resulting disinhibition of VTA DA
      neurones might therefore contribute to the sensitised dopaminergic responses
      observed in the rat mesocorticolimbic system following repeated administration of
      nicotine.

PMID- 15494080
TI  - SOCS proteins in T helper cell differentiation: implications for allergic
      disorders?
AB  - Asthma, allergic rhinitis and atopic dermatitis are allergic immune disorders
      characterised by a predominance of T helper 2 (Th2) cells, the resulting
      elevation of allergen-specific IgE, and mast-cell- and basophil-associated
      inflammation. The cytokine environment at the site of the initial antigen
      stimulation determines the direction of Th-cell differentiation into Th1 or Th2
      cells. The SOCS (suppressor of cytokine signalling) proteins are implicated in
      the control of the balance between Th1 and Th2 cells in this process. SOCS3 is
      predominantly expressed in Th2 cells and inhibits Th1 differentiation;
      conversely, SOCS5 is expressed predominantly in Th1 cells and inhibits Th2
      differentiation. Here, we discuss the role of SOCS proteins in Th-cell
      differentiation and explore the potential of SOCS proteins as targets for
      therapeutic strategies in allergic disorders.

PMID- 15494081
TI  - Nine years' experience of telecardiology in primary care.
AB  - The ITMS telecardiology network started in April 1995. Over nine years, about
      7000 peripheral medical users (mainly general practitioners), who were
      experienced in using transtelephonic electrocardiography and who were spread
      throughout Italy, conducted teleconsultations with the Telecardiology Centre. A
      total of 106,942 patients were evaluated. Teleconsultation was carried out for
      non-cardiac symptoms or routine control for 30,444 patients (28%) and for
      symptoms suggestive of heart disease for 76,498 (72%). After teleconsultation,
      61,908 patients (58%) were reported to have no heart disease, 27,947 patients
      (26%) had their drug dose adjusted and remained at home, 11,503 patients (11%)
      were sent to their cardiologist for further investigations and 5584 patients (5%)
      were urgently hospitalized. Among the hospitalized patients, the echocardiogram
      demonstrated an ST-elevation coronary syndrome in 1785 patients (32%), a non-ST
      elevation coronary syndrome in 2236 (40%) and a life-threatening arrhythmia in
      1354 (24%). Telecardiology improves the decision making of general practitioners,
      avoids unnecessary hospitalizations, reduces the time before treatment in cardiac
      emergencies, rationalizes health-care costs and promotes home care.

PMID- 15494082
TI  - A multi-phase telepsychiatry programme in Michigan: organizational factors
      affecting utilization and user perceptions.
AB  - Over the last few years, telepsychiatry services in Michigan have been developed
      by LifeWays, a Medicaid-managed behavioural health-care organization. The project
      had four phases, involving the introduction of telepsychiatry services between a
      rural and an urban clinic, to a crisis intervention centre, to a youth detention
      centre and to patients' homes. The role of organizational issues in the success
      of the programme was examined through patient interviews, provider interviews,
      patient and provider pre- and post-project focus groups, and service documents.
      Utilization data were obtained from activity logs and patient charts. During the
      study, 297 clients received 578 teleconsultations. Almost 97% of the
      telepsychiatry visits were scheduled. Telemedicine usage varied between the four
      project phases. The reasons for its variation in use included provider roles,
      existing organizational strategic goals and resources, the inherent
      organizational culture and quirks, and leadership and managerial factors. The
      major difficulties stemmed from the providers and the organization itself. There
      is tremendous potential for telepsychiatry and the ways in which organizational
      variables can be managed to influence the success of telepsychiatry programmes
      deserve further study.

PMID- 15494083
TI  - Automatic fall detectors and the fear of falling.
AB  - We studied the effect of automatic fall detection units on the fear of falling.
      Participants were community alarm users living in the community aged over 75
      years or those aged 60-74 years who had experienced a fall in the previous six
      months. Of those approached, 31% consented to take part; the main reason given
      for potential participants declining involvement was that they were happy with
      the technology they already had. Subjects were assigned to a control group (n =
      21) or intervention group (n = 34) based on age, the number of self-reported
      falls in the previous six months and their score on the self-administered Falls
      Efficacy Scale (FES), which measures fear of falling on a scale of 0-100, with
      higher scores indicating less fear. The monitoring period lasted a mean of 17
      weeks (SD 3.1). There was no significant difference between the intervention and
      control groups in their mean ratings of fear of falls (40.3 vs 37.5, difference
      2.8, 95% CI 6.2 to 11.8), health-related quality of life or morale. Differences
      in fear of falling between an intervention subgroup who wore their detector at
      least occasionally (62%) and those who did not (38%) suggested that some people
      may benefit from a fall detector while others may lose confidence if they are
      provided with one. Most users who wore their detectors at least occasionally felt
      more confident and independent and considered that the detector improved their
      safety.

PMID- 15494084
TI  - T.120 application sharing for the remote configuration of prostheses.
AB  - We conducted a study to determine whether application sharing and desktop
      videoconferencing using the Internet constituted a viable method for remotely
      configuring a microprocessor-controlled lower-extremity prosthesis. A DSL
      broadband connection (operated at 256 kbit/s) was used to connect two prosthetic
      care facilities over the public Internet. PC-based videoconferencing was used
      with application sharing for the remote configuration of the prosthesis and to
      view information on the load and angle of the prosthetic knee. Fifteen people
      with trans-femoral amputations had the settings for their prosthesis scrambled
      before a specialist at another site remotely configured the device. There were no
      significant differences between the original and online settings. Clinicians at
      both sites considered that 14 out of 15 sessions were successful (one trial
      involved technical problems with the knee unit that were unrelated to the
      telemedicine trial). The clients rated their satisfaction with the technique as
      excellent (47%), above average (33%) or average (20%). The present study shows
      that a combination of desktop videoconferencing and T.120 application sharing can
      be used for the remote configuration of assistive devices.

PMID- 15494085
TI  - Web-based diabetes control.
AB  - We developed a diabetes management system with a Web interface that allowed
      patients to transmit their physiological data using either a PC Web browser or a
      mobile phone capable of working with the WAP protocol. The system could generate
      automatic responses to input values in accordance with a set of ranges previously
      defined for each user. User analysis was carried out with personal and online
      questionnaires. During a nine-month study period on the island of Tenerife, 12
      patients were recruited. On average, they used the system every 2.0 days (SD 2.1)
      and the doctors reviewed their patient data every 4.0 days (SD 3.9). The average
      number of visits to the Website was 477 per month. Users were satisfied with the
      continuity and self-efficacy of care, but lack of time was a drawback for 38% of
      them and 75% expressed a preference for sending their data via the mobile phone
      short message service (SMS).

PMID- 15494086
TI  - Mobile phone text messaging in the management of diabetes.
AB  - We conducted a trial of mobile phone text messaging (short message service; SMS)
      for diabetes management. In an eight-month period, 23 diabetic patients used the
      service. Patients used SMS to transmit data such as blood glucose levels and body
      weight to a server. The server automatically answered with an SMS acknowledgement
      message. A monthly calculated glycosylated haemoglobin result was also
      automatically sent to the patient by SMS. During the trial the patients sent an
      average of 33 messages per month. Although users showed good acceptance of the
      SMS diabetes system, they expressed various concerns, such as the inability to
      enter data from previous days. Nonetheless, the trial results suggest that SMS
      may provide a simple, fast and efficient adjunct to the management of diabetes.
      It was particularly useful for elderly persons and teenagers, age groups that are
      known to have difficulty in controlling their diabetes.

PMID- 15494087
TI  - Telemedicine and coping skills groups for Pacific Island veterans with post
      traumatic stress disorder: a pilot study.
AB  - Patients with post-traumatic stress disorder (PTSD) were randomly assigned to
      either an eight-week videoconferencing PTSD coping skills group or a traditional
      face-to-face PTSD coping skills group. Levels of attrition and compliance,
      patient satisfaction, clinician satisfaction and patients' retention of
      information were compared between the two conditions. Of the 41 referred
      veterans, 20 were eligible and agreed to participate in the study. Three of these
      participants withdrew from the study before randomization. By the end of the
      study, 89% of the patients remained in the videoconferencing group, whereas only
      50% remained in the face-to-face group. Patients in the face-to-face group
      attended an average of 4.9 sessions and patients in the videoconferencing group
      attended 6.3 sessions (this difference was not significant). There was no
      difference between levels of patient satisfaction or clinician satisfaction at
      weeks 4 or 8. Patients' retention of information was similar in the two groups.
      The results show that videoconferencing can be used to provide coping skills
      groups for veteran patients with PTSD who reside in remote rural locations.

PMID- 15494088
TI  - Operators' experiences of emergency calls.
AB  - In Sweden, the operators at emergency dispatch centres are responsible for
      allocating resources (e.g. ambulances, fire brigade, police) in response to
      calls. We analysed situations that the emergency operators experienced as
      difficult and their reflections on how they managed them. Interviews were
      conducted with all 16 emergency operators at a centre that serves a population of
      275,000 and receives about 700,000 emergency calls annually. A phenomenological
      hermeneutic approach was used for the analysis. Situations that operators
      experienced as difficult were characterized by uncertainty, communication
      difficulties and insufficient resources. Skills, knowledge and experience were
      regarded as important in the management of these situations, as were personal
      qualities such as sensitivity, insight, empathy and intuition. The emergency
      operators stated that they needed more guidance, feedback and education in their
      work. This would lead to an increased sense of certainty, which would lead to
      decreased stress and a better outcome for those in need.

PMID- 15494089
TI  - A multi-functional, portable device with wireless transmission for home
      monitoring of children with a learning disability.
AB  - A portable monitoring device was developed to assist in the management of
      children with a learning disability. The device was designed for continuous home
      monitoring of blood oxygen saturation, heart and respiration rates, and patient
      activity. It could be worn on a belt, while the patient continued normal
      activities. Data were stored on a multimedia card and automatically transmitted
      to a PC at prescribed intervals via a Bluetooth wireless link. From the PC the
      data were transmitted to a Web server, where the information was made available
      to the staff involved in the patient's care. Preliminary clinical studies were
      performed with nine patients (four with Down's syndrome, three with cerebral
      palsy and two with mental retardation). Patients and families considered the
      device easy to use and to wear. The monitoring device identified events of
      possible clinical interest. Although it was designed for monitoring children with
      a learning disability, it may also be useful with other groups, such as elderly
      people.

PMID- 15494090
TI  - In-service nursing education delivered by videoconference.
AB  - Thirty nursing auxiliaries at a Brazilian hospital were trained in intramuscular
      injection at the ventrogluteal site in a lecture delivered by videoconference
      (over an IP connection at up to 512 kbit/s). Participants were able thereafter to
      practise on the same manikins used for demonstration during the lecture, until
      they felt confident in carrying out the procedure. They then completed an
      evaluation questionnaire on the use of videoconferencing as a teaching method.
      Most of their responses were favourable. The principal reasons given for
      attending the videoconference lecture were the ability to combine work and
      education, the opportunity to participate in an innovative approach and an
      interest in the subject of the lecture. The present study demonstrates the
      potential of videoconferencing for distance education in nursing.

PMID- 15494091
TI  - Comparison of telepathology services.

PMID- 15494092
TI  - Artefacts in digital whole-body photography.

PMID- 15494094
TI  - Meningioma and schwannoma risk in adults in relation to family history of cancer.
AB  - Relatively little is known about factors that contribute to the development of
      meningioma and vestibular schwannoma, two intracranial nervous system tumors. We
      evaluated the risk of these tumors in relation to family history of malignant or
      benign tumors. Incident cases of meningioma (n = 197) or schwannoma (n = 96) were
      identified at three U. S. referral hospitals between June 1994 and August 1998.
      Controls (n = 799) admitted to the same hospitals for nonmalignant conditions
      were matched to cases on age, sex, race/ethnicity, hospital, and proximity of
      residence to hospital. We found that risk of meningioma was increased among
      persons reporting a family history of a benign brain tumor (odds ratio [OR], 4.5;
      95% confidence interval [CI], 1.0-21.0; n = 5) or melanoma (OR, 4.2; 95% CI, 1.2
      15.0; n 5). A family history of breast cancer was associated with an elevated
      meningioma risk among participants aged 18 to 49 years (OR, 3.9; 95% CI, 1.4
      11.0; n = 8) but a reduced risk among older respondents (OR, 0.2; 95% CI, 0.1
      0.7; n = 3). Family history of cancer did not differ between schwannoma cases and
      controls, although the statistical power to detect associations was limited. Some
      relative risk estimates were based on a small number of observations and may have
      arisen by chance. Inheritance of predisposing genes, shared environmental
      factors, or both within families with a history of benign brain tumors, melanoma,
      or possibly breast cancer may be related to altered meningioma risk.

PMID- 15494095
TI  - Detrended fluctuation analysis of genome-wide copy number profiles of
      glioblastomas using array-based comparative genomic hybridization.
AB  - We examined whole genomic aberrations of biopsied samples from 19 independent
      glioblastomas by array-based comparative genomic hybridization analysis. The
      highest frequencies of copy number gains were observed on RFC2 (73.3%), EGFR
      (63.2%), and FGR, ELN, CDKN1C , FES, TOP2A, and ARSA (57.9% each). The highest
      frequencies of copy number losses were detected on TBR1 (52.6%), BMI1 (52.6%),
      EGR2 (47.4%), DMBT1 (47.4%), MTAP (42.1%), and FGFR2 (42.1%). The copy number
      gains of CDKN1C and INS and the copy number losses of TBR1 were significantly
      correlated with longer survival of patients. High-level amplifications were
      identified on EGFR, SAS/CDK4, PDGFRA, MDM2, and ARSA. These genes are assumed to
      be involved in tumorigenesis or progression of glioblastomas. The first attempts
      to apply detrended fluctuation analysis to copy number profiles by considering
      the reading direction as the time axis demonstrated that higher long-term fractal
      scaling exponents (alpha2) correlated well with longer survival of glioblastoma
      patients. The present study indicates that array-based comparative genomic
      hybridization analysis has great potential for assessment of copy number changes
      and altered chromosomal regions of brain tumors. Furthermore, we show that
      nonlinear analysis methods of whole genome copy number profiles may provide
      prognostic information about glioblastoma patients.

PMID- 15494096
TI  - Diagnostic and prognostic significance of genetic regional heterogeneity in
      meningiomas.
AB  - We analyzed the frequency and regional distribution of cells with genetic
      abnormalities of chromosomes 1, 14, and 22 in meningiomas. This data was
      evaluated for correlation to the clinical outcome of the patients. Eight defined
      areas of each of 77 paraffin-embedded meningioma samples (59 grade I, 13 grade
      II, and 5 grade III) were analyzed by fluorescent in situ hybridization using
      bacterial artificial chromosome probes localized to chromosomes 1p36.32, 1q25.3,
      14q13.3, 14q32.12, 22q11.2, and 22q12.1-3. Chromosome deletion was considered to
      be regionally heterogeneous if 7 regions showed cells with chromosome deletions.
      Deletion of 1p occurred in 35% of the grade I tumors. Distribution of cells with
      1p deletion was regionally heterogeneous in 25% and homogeneous in 10% of grade I
      tumors. Distribution of cells with deletion of 1p was regionally heterogeneous in
      23% and homogeneous in 69% of the grade II tumors. All grade III meningiomas had
      homogeneous distribution of cells with deletion of chromosome 1p. Distribution of
      cells with deletion of 14q was regionally heterogeneous in 27% and homogeneous in
      2% of the grade I meningiomas, heterogeneous in 31% and homogeneous in 62% of the
      grade II tumors, and heterogeneous in 40% and homogeneous in 60% of the grade III
      meningiomas. Distribution of cells with deletion of 22q was regionally
      heterogeneous in 15% and homogeneous in 3% of the grade I tumors, heterogeneous
      in 15% and homogeneous in 31% of grade II tumors, and homogeneous in 20% of the
      grade III meningiomas. Distribution of cells with trisomy 22q was regionally
      heterogeneous in 10% of grade I tumors, heterogeneous in 23% of grade II, and
      homogeneous in 80% of grade III meningiomas. The proportion of patients with a
      deletion of 22q (either homogeneous or heterogeneous) who had recurrence was
      greater than the proportion of those without 22q deletion who had recurrence, and
      deletion of 22q was significantly associated with radiologically detected
      recurrence (P < 0.05). We conclude that the appearance of chromosomal aberrations
      in different areas of the tumor demonstrates the importance of regional
      heterogeneity in the biological behavior of meningiomas.

PMID- 15494099
TI  - Commentary: does screening mammography lead to breast cancer overdiagnosis?

PMID- 15494097
TI  - Penetration of intra-arterially administered vincristine in experimental brain
      tumor.
AB  - Vincristine is an integral part of the "PCV" regimen that is commonly
      administered to treat primary brain tumors. The efficacy of vincristine as a
      single agent in these tumors has been poorly studied. This study was designed to
      determine whether vincristine enters normal rat brain or an intracranially or
      subcutaneously implanted glioma and to assess the presence of the efflux pump P
      glycoprotein (P-gp) on tumor and vascular endothelial cells. The 9L rat
      gliosarcoma was implanted intracranially and subcutaneously in three Fischer 344
      rats. On day 7, [3H]vincristine (50 microCi, 4.8 microg) was injected into the
      carotid artery, and the animals were euthanized 10 or 20 min later. Quantitative
      autoradiography revealed that vincristine levels in the liver were 6- to 11-fold
      greater than in the i.c. tumor, and 15- to 37-fold greater than in normal brain,
      the reverse of the expected pattern with intraarterial delivery. Vincristine
      levels in the s.c. tumor were 2-fold higher than levels in the i.c. tumor. P-gp
      was detected with JSB1 antibody in vascular endothelium of both normal brain and
      the i.c. tumor, but not in the tumor cells in either location, or in endothelial
      cells in the s.c. tumor. These results demonstrate that vincristine has
      negligible penetration of normal rat brain or i.c. 9L glioma despite intra
      arterial delivery and the presence of blood-brain barrier dysfunction as
      demonstrated by Evan's blue. Furthermore, this study suggests that P-gp-mediated
      efflux from endothelium may explain these findings. The lack of penetration of
      vincristine into brain tumor and the paucity of single-agent activity studies
      suggest that vincristine should not be used in the treatment of primary brain
      tumors.

PMID- 15494100
TI  - Long-term safety and tolerability of continuous-combined hormone therapy in
      postmenopausal women: results from a seven-year randomised comparison of low and
      standard doses.
AB  - OBJECTIVE: To establish the long-term safety profile of four oestradiol
      valerate/medroxyprogesterone acetate (E(2)V/MPA) regimens. STUDY DESIGN: 419
      postmenopausal women in parallel treatment groups started treatment with 1 or 2
      mg E(2)V with either 2.5 or 5 mg MPA for 84 cycles of 28 days in a randomised,
      comparative study. The first 24 month double-blind efficacy period has been
      previously reported. This report focuses on the open safety period after the
      first two years until completion of 84 treatment cycles. RESULTS: A total of 275
      women (65.6%) completed the seven-year study. All regimens provided good bleeding
      control and endometrial protection, with no cases of endometrial hyperplasia or
      cancer diagnosed. All regimens were well tolerated with a low frequency of
      adverse effects, mostly occurring within the first two years. The most common
      drug-related adverse events included breakthrough bleeding, headache/migraine,
      abdominal pain and mood changes. Very few women (n = 4) receiving the lowest dose
      option (1 mg E(2)V + 2.5 mg MPA) reported adverse effects (p<0.009 vs other
      groups). No serious cardiovascular events occurred in any of the groups, the
      incidence of strokes was lower than the national incidence for the age group and
      the incidence of breast cancer was comparable with the national incidence (95%
      CI). In the lowest dose group, no women had to stop therapy prematurely due to
      serious adverse events. CONCLUSIONS: The results support the use of lower doses
      for longterm hormone therapies.

PMID- 15494101
TI  - The influence of postmenopausal hormone replacement therapy on cognitive
      functioning: results from an observational study.
AB  - OBJECTIVES: The aim of this study was to evaluate the impact of hormone
      replacement therapy (HRT) upon memory deficit in a group of urban Australian
      women. PARTICIPANTS AND SETTING: A cohort of 493 women aged 40-80 years was
      tested as part of the Longitudinal Study of Ageing in Women (LAW study) at the
      Royal Brisbane and Women's Hospital, Brisbane, Australia. MAIN OUTCOME MEASURES:
      The current memory functioning of participants was evaluated using the Wechsler
      Memory Scale - version three (WMS-III) while pre-morbid cognitive functioning was
      estimated from scores on the National Adult Reading Test (NART). Memory deficit
      was estimated by comparing NART scores with the age-corrected scale scores of the
      WMS-III. RESULTS: Overall, NART scores correlated with WMS-III scores, consistent
      with the expected relationship between pre-morbid functioning and current
      functioning. For the sample as a whole, memory deficit was evident but mostly,
      age appropriate. There was considerable variation as to the extent of memory
      deficit within the sample. When memory functioning for women with a history of
      five or more years of combined oestrogen plus progestogen HRT or oestrogen
      replacement therapy (ERT) was compared with that of women who had never used HRT
      or ERT there was no evidence of any effect for either HRT or ERT on memory
      deficit. CONCLUSIONS: The use of HRT or ERT had neither a protective nor an
      adverse effect on memory deficit.

PMID- 15494102
TI  - 1170 consecutive hysterectomies: indications and pathology.
AB  - OBJECTIVE: An analysis of consecutive hysterectomies during 1997-99 exploring the
      relationship between histological findings, operation performed and clinical
      indication was conducted to observe any trends. METHODS: A retrospective review
      of histology reports for hysterectomies performed in a large district teaching
      hospital. RESULTS: The rate of hysterectomy for women aged over 25 years was 23
      per 10,000 women. Menstrual disturbance including endometriosis was the
      indication in 45%, pelvic tumours including fibroids in 21%, prolapse in 17% and
      malignant or pre-malignant conditions in 15%; 1% were performed in relation to
      childbirth. 79% were total abdominal hysterectomies, 4% subtotal and 17% vaginal.
      50% included removal of both ovaries and in 8% omentectomy was also performed.
      The uterus was histologically normal in 20% of abdominal hysterectomies, the rate
      rising to 70% for vaginal hysterectomies. CONCLUSIONS: The rate of hysterectomy
      has not changed over the past 15 years, despite the introduction of alternative
      medical and surgical therapies for managing menstrual problems and fibroids.
      There may have been a greater proportion performed for malignant and premalignant
      conditions and genital tract prolapse. There were fewer specimens with no
      evidence of pathology than is often suggested.

PMID- 15494103
TI  - Diet and dementia.
AB  - The ageing brain adapts to the accumulation of damage caused by oxidative stress
      and inflammation. Adaptive processes include neuroprotective and neurorestorative
      mechanisms. Individual differences in susceptibility to dementia arise when these
      mechanisms are impaired or are overwhelmed by the molecular pathology of
      Alzheimer's disease. Neuroprotection relies upon extrinsic and intrinsic
      defences. An adequate intake of antioxidant micronutrients (eg, vitamin C and
      vitamin E) and anti-inflammatory macronutrients (eg, omega-3 polyunsaturated
      fatty acids) forms an essential component of extrinsic defences against brain
      ageing. There are many epidemiological data to support an association between an
      inadequate intake of antioxidants and/or fish oils (an important source of omega
      3 polyunsaturated fatty acids) and a greater than expected incidence of late
      onset dementia. These associations are confounded by established links between
      poverty, poor diet and failing health, especially in old age. Such links may be
      sufficient to explain some of the effects of an inadequate diet on the retention
      of cognitive function and increased risk of dementia in old age. More compelling
      is the association between increased plasma homocysteine concentration and later
      increased risk of dementia. This association is possibly caused by an inadequate
      intake of vitamin B(12)/folate.

PMID- 15494104
TI  - Oestrogen: brain ageing, cognition and neuropsychiatric disorder.
AB  - The effects of oestrogen on brain ageing, cognition and neuropsychiatric disorder
      are an important public health issue, which, despite intensive research, has yet
      to be resolved. Evidence from basic science demonstrates that oestrogen has
      multiple protective effects on neurons and neurotransmitter systems. However, the
      evidence for oestrogen having a clinical role in the treatment and prevention of
      neuropsychiatric disorders is not well established. Here we review research into
      the effects of oestrogen on brain maturation and function and discuss the role
      for oestrogen replacement therapy (ERT) as a therapeutic tool.

PMID- 15494105
TI  - Malignancy arising in residual endometriosis following hysterectomy and hormone
      replacement therapy.
AB  - Two women with adenocarcinoma of the endometrium and a past history of
      disseminated pelvic endometriosis presented with vaginal bleeding. One also had
      obstructive uropathy. The two patients had undergone total abdominal hysterectomy
      with removal of one or both ovaries three and 13 years previously and
      subsequently were treated with unopposed oestrogen replacement therapy.
      Adenocarcinoma of the endometrium following endometriosis is a rare condition and
      few cases are reported in the literature. A summary of the cases and related
      literature are presented.

PMID- 15494106
TI  - Myalgia after stopping hormone replacement therapy.

PMID- 15494107
TI  - Porcine chromaffin cells, culture, and transplant for antinociceptive effects in
      rodents and primates.
AB  - It has been shown that xenografts and allografts of spinally transplanted adrenal
      chromaffin cells produce antinociception in animals and pain relief in patients
      with cancer pain. As there is a very limited availability of human adrenal tissue
      to serve as allografts, the clinical need for xenogeneic chromaffin cells as
      transplants is obvious. Bovine adrenal glands as a steady source of chromaffin
      cells have been extensively studied. There is however concern about the possible
      infection in humans with retrovirus following transplantation. The purpose of
      this study is to use the pig as a preferred donor animal species for
      xenotransplantation into rat and monkey. As pigs have been cloned, this opens the
      door to gene-targeted technologies and allows for genetic modifications, which
      possibly could improve the efficacy and safety of chromaffin cell
      transplantation. Porcine chromaffin cells were isolated from adrenal glands of 6
      8-month-old pigs. After culturing cells for 1 week in a medium containing serum,
      the release of met-enkephalin and norepinephrine from the cells was detected by
      high-performance liquid chromatography and radioimmunoassay with nicotine
      stimulation, lasting approximately 3 weeks. Transplantation of these cells into
      the subarachnoid space of rats produced antinociceptive effects on Adelta and C
      fiber-mediated responses lasting 2-3 weeks. Similar findings were observed in
      studies with macaque monkeys. Compared with the same number of bovine chromaffin
      cells, porcine chromaffin cells showed a more robust and longer antinociceptive
      effect, and could be a better source of cells for human transplantation.

PMID- 15494109
TI  - Tethered cord syndrome in adults and children.

PMID- 15494110
TI  - Tethered cord syndrome: overview of diagnosis and treatment.
AB  - This article covers the basis of tethered cord syndrome as a stretch-induced
      spinal cord disorder, including pathophysiology, signs and symptoms, imaging
      diagnosis, indication for surgical treatment, and surgical procedures. Anomalies
      that cause mechanical spinal cord tethering are listed, and the surgical
      untethering technique for each anomaly is described.

PMID- 15494111
TI  - Pathophysiology of tethered cord syndrome and other complex factors.
AB  - There are different interpretations of tethered cord syndrome (TCS) partly due to
      difficulty in understanding the concept of this syndrome as a functional disorder
      not merely based on gross anatomy of congenital anomalies. The essential
      mechanical factor of cord tethering is that any of the inelastic structures
      fastening the caudal end of the spinal cord produces traction effects on the
      lumbosacral cord. The production of such traction is the key to understanding
      this disorder. In a significant number of patients who present with the typical
      clinical signs and symptoms of TCS, the diameter of the filum terminale is found
      within normal limits and the caudal end of the spinal cord is located in the
      normal position. Therefore, the definition of TCS requires the demonstration that
      there is a posterior displacement of the conus and filum by MRI, lack of
      viscoelasticity by the stretch test of the filum during surgery, and fibrous
      displacement of glial tissue within the filum by histological studies. This is
      because there is inconsistency from such studies as ultrasonography, MRI and CT
      myelography, which attempt to establish the presence of a tight filum terminale.
      A goal of this article is to provide basic understanding of TCS so that
      clinicians can use the concept of stretch-induced spinal cord dysfunction for
      proper diagnosis and treatment of this disorder.

PMID- 15494112
TI  - Can the conus medullaris in normal position be tethered?
AB  - Many have equated the term tethered spinal cord to a conus that is pathologically
      elongated. Most authorities have declared radiologic coni located inferior to the
      L-2 as pathologic. However, we have described previously a small series of
      patients in whom symptoms of a tethered spinal cord were evident clinically yet
      radiologically the conus medullaris was found to lie at a widely acceptable
      normal anatomic site. Following a review of the extant literature prior to our
      publication in 1993, several authors had operated on patients for symptoms of a
      distally tethered spinal cord in whom a conus was found to terminate at a
      'normal' vertebral level. We believe that there is indeed a subset of the
      tethered cord patient population in whom the tip of the conus lies at even
      liberally accepted normal levels. We would encourage clinicians treating patients
      with symptoms of tethered cord syndrome not to treat the patient based simply on
      imaging but imaging coupled with clinical symptoms and physical exam. It is
      important to point out that in lieu of the many publications of conus termination
      that one accepts that there is no one single 'normal' position of the terminal
      cord but rather a normal range. Perhaps a superior way of interpreting 'tethered'
      cord is to view this as tautness of the cord and not necessarily elongation of
      the distal cord in every case.

PMID- 15494113
TI  - Adult tethered cord syndrome: relative to spinal cord length and filum thickness.
AB  - The adults with tethered cord syndrome (TCS) are divided into two groups: group-1
      adult TCS patients with spinal dysraphism; and group-2 patients without
      dysraphism who develop signs and symptoms in adulthood. A significant number of
      group-2 patients failed to show elongation of the spinal cord and abnormally
      thick filum terminale. This paper reports the combinations of the location of the
      caudal end of the spinal cord and the thickness of the filum terminale in 104
      patients with group-2 adult TCS. The caudal end of the spinal cord was found at
      the L2-3 intervertebral space or above in 37 patients (35.6%) and below L2-3
      level in 67 patients (64.4%). The diameter of the filum was <2 mm in 60 patients
      (57.7%) and > or =2 mm in 44 patients (42.3%). These data clearly indicate that
      the pre-operative diagnosis of adult TCS must rely primarily on the neurological
      symptomatology and the specific imaging feature, posterior displacement of the
      conus and filum that attach the posterior arachnid membrane.

PMID- 15494114
TI  - The tethered cord syndrome in adults with spina bifida occulta.
AB  - The management of adult-onset tethered cord syndrome (TCA) remains controversial,
      although the necessity of early surgery in children with TCS is well established.
      In this paper, we review the major publications that discuss the congenital
      tethered spinal cord (spina bifida occulta) presenting in adulthood. Data
      concerning acquired tethered cord from prior myelomeningocele repair were
      excluded. TCS in adults is an uncommon entity that can become symptomatic. The
      long-term surgical outcome after tethered cord release in this patient population
      is generally favorable, as most patients report improvement or stabilization of
      their symptoms. In addition, the overall post-operative complication rate is low.
      Although special consideration should be given to older patients with a poor
      general medical condition, it seems reasonable to recommend early surgical
      treatment in both symptomatic and asymptomatic adults.

PMID- 15494115
TI  - Symptomatic protocols for adult tethered cord syndrome.
AB  - Diagnosis of tethered cord syndrome (TCS) is complicated because anatomical
      information is not adequate for this task. For example, recent studies have shown
      that the combination of an elongated cord and a thick filum terminale,
      demonstrated by MRI or at operation, is no longer an essential feature for the
      diagnosis of TCS. For TCS diagnosis, emphasis should rather be on its
      characteristic symptomatology and accentuated by postural changes, since TCS is a
      functional disorder of the lumbosacral spinal cord. In this report, the authors
      present the list of signs and symptoms pertinent to TCS in adult and late teenage
      patients to serve as a diagnostic means.

PMID- 15494116
TI  - Tethered cord syndrome in childhood: diagnostic features and relationship to
      congenital anomalies.
AB  - Tethered Cord Syndrome (TCS) is a stretch-induced functional disorder of the
      spinal cord that often develops and presents in childhood in association with
      spinal dysraphism. While the subtlety with which TCS can present makes it
      challenging to diagnose, awareness of the common neurological, musculoskeletal
      and urologic symptoms are of great value to the clinician, and can aid timely
      referral for neurosurgical evaluation. This article reviews these symptoms, as
      well as the clinical and radiological findings of the most common dysraphic
      conditions associated with TCS.

PMID- 15494117
TI  - Clinical utility of echocontrast agents in neurosonology.
AB  - INTRODUCTION: Neurosonological investigations of the extracranial and
      intracranial brain supplying arteries are helpful in the assessment of stroke and
      stroke-prone patients. METHODS: In this paper we review the indications,
      application and advantages of second-generation (gas-filled) microbubble contrast
      agents such as SonoVue. RESULTS: Gas-filled microbubbles have a strong echo
      enhancing effect and produce enhancement for several minutes, enabling the
      sonographer to perform the investigation with a single injection or two or three
      repeated injections without the need for continuous administration. Echocontrast
      agents provide better delineation of normal blood flow, occlusions, pseudo
      occlusions, stenoses, and collaterals in the extracranial and intracranial
      vascular beds. They are of particular value during transcranial color-coded
      transcranial duplex investigations via the temporal and occipital window.
      CONCLUSIONS: Echocontrast agents give additional information on the patient's
      vascular situation that is often crucial to planning further diagnostic and
      therapeutic steps. The use of second-generation gas-filled microbubbles, such as
      SonoVue in transcranial neurosonology, may help to avoid unnecessary, expensive
      and potentially harmful additional investigations such as intra-arterial DSA.
      Future applications include the visualization of brain tissue perfusion.

PMID- 15494118
TI  - Intra-vital ultrasonographic monitoring of intra-cerebral tumor growth in a rat
      glioma model: technical note.
AB  - The assessment of therapeutic effects in rodent glioma models by comparison of
      post mortem tumor sizes has to deal with differing individual growth kinetics and
      the possibility of spontaneous tumor regression. This technical note describes
      the intravital ultrasonographical monitoring of cerebral tumor growth in
      individual animals. In the experiments C6 lacZ glioma cells were injected
      intracerebrally into female Wistar rats. Extended craniectomy allowed for
      transcutaneous sonographic examination of the tumor growth. Four animals were
      followed ultrasonographically, the volumes of the tumors were calculated and
      plotted graphically, and on day 21 histological evaluation was performed. Our
      results show that ultrasonography is an easy and reliable imaging modality for
      frequent assessment of tumor growth kinetics in the intra-cerebral rat glioma
      model. It allows for the intravital monitoring of treatment with new therapeutic
      strategies and increases the reliability of the model by visualization of the
      tumor size before initiation of treatment.

PMID- 15494119
TI  - Bilateral acute epidural hematoma after evacuation of acute subdural hematoma:
      brain shift and the dynamics of extraaxial collections.
AB  - Acute epidural hematoma following supratentorial decompressive craniectomy is a
      very seldom described but serious complication. The occurrence of intraoperative
      brain swelling may suggest the development of a contralateral hematoma. A unique
      case of bilateral acute epidural following decompressive craniectomy and
      evacuation of acute subdural hematoma is presented. Awareness of unexplained
      elevation of intracranial pressure is of paramount importance when routine
      immediate postoperative computed tomography is not performed. This case provides
      insight into the well-known but poorly understood dynamic process of brain shift
      and extraaxial collections.

PMID- 15494120
TI  - Severity dependent up-regulations of LOX-1 and MCP-1 in early sclerotic changes
      of common carotid arteries in spontaneously hypertensive rats.
AB  - Lectin-like oxidized low-density lipoprotein receptor (LOX-1) and monocyte
      chemoattractant protein-1 (MCP-1) are molecules involving in the initiation and
      progression of atherosclerosis. In order to examine a possible difference in LOX
      1 and MCP-1 expressions depending on the severity of early stage of
      atherosclerosis, we investigated atherosclerotic changes by exposure to
      hypertension and hyperlipidemia in common carotid arteries (CCAs) of stroke-prone
      spontaneously hypertensive rat (SHR-SP). Three rat model groups such as control
      [Wistar Kyoto rat (WKY) group], hypertension (SHR-SP group) and hypertension +
      hyperlipidemia [SHR-SP + high fat and cholesterol (HFC) group] were used. Body
      weights, brain weights, systolic blood pressures and serum levels of total
      cholesterol, low-density lipoprotein and triglyceride were measured at 0, 5, 10
      and 15 days after appropriate diet. Immunohistochemistry showed that the positive
      area and the strength of LOX-1 and MCP-1 were larger in the SHR-SP + HFC group
      than in the SHR-SP group, while no immunoreactivities were found in the WKY
      group. Conventional RT-PCR and real-time PCR analyses showed that mRNAs of those
      in the SHR-SP group were higher with greater up-regulation in the SHR-SP + HFC
      group. LOX-1 and MCP-1 expressions were coordinately up-regulated at mRNA and
      protein levels in an early stage of sclerosis depending on the severity of
      atherosclerotic stress. Activations of LOX-1 and MCP-1 are collectively involved
      in the early stage of atherosclerosis.

PMID- 15494121
TI  - Primary primitive neuroectodermal tumor within the spinal epidural space: report
      of a case and review of the literature.
AB  - Primary intraspinal primitive neuroectodermal tumors (PNETs) are rare tumors and
      a have poor prognosis. In reviews of the literature, it is seen that primary
      intraspinal PNETs may arise at all levels of the spine and may be intramedullary,
      intradural-extramedullary, or epidural. Spinal epidural location of PNET is
      extremely rare and out of 22 cases of primary spinal PNETs reported to date, only
      two were epidural. Tumors within the epidural space of the spinal canal are most
      often metastatic neoplasms from different primary sites. Here we report a case of
      primary extradural PNET located in the thoracic spine in a 16-year-old boy and
      review the relevant literature.

PMID- 15494122
TI  - Calcification in carotid atheromatous plaque: delineation by 3D-CT angiography,
      compared with pathological findings.
AB  - The authors investigated calcification in the carotid plaque of patients with
      carotid stenosis, using three-dimensional CT angiography (3D-CTA) and comparing
      the images with findings from pathological inspection. Calcification was clearly
      visualized using volume rendering (VR) images constructed with a refined
      workstation as well as maximum intensity projection and multiplanar
      reconstruction images. Calcification in VR images was classified into bean- and
      island-like shaped groups, while calcification in microscopic examination was
      classified into granular, lump and laminar types. Granular type of calcification
      tended to be found at the intimal side of the plaque, while lump/laminar
      calcification was preferentially located at the side of the internal elastic
      fiber. Though carotid endarterectomy successfully removed calcification at both
      sides, the presence of a granular calcification assembly when massive
      calcification is observed with 3D-CTA might alert us to the importance of
      predicting the hardness of plaque in carotid angioplasty and stenting.

PMID- 15494123
TI  - IkappaBalphaM suppresses angiogenesis and tumorigenesis promoted by a
      constitutively active mutant EGFR in human glioma cells.
AB  - Human glioma cell lines (G36DeltaEGFR and IN500DeltaEGFR) have been shown to
      display an enhanced tumorigenic phenotype, when transfected with a constitutively
      active form of the epidermal growth factor receptor (DeltaEGFR). These cells were
      transfected with a mutant IkappaBalpha (IkappaBalphaM) that is resistant to
      phosphorylation and degradation, and hence blocks NF-kappaB activity. Recently,
      EGFR has been shown to increase the activity of NF-kappaB and to induce
      angiogenesis. In this report, we asked if IkappaBalphaM gene transfer into human
      glioma cell lines would inhibit tumorigenicity and angiogenesis in glioma.
      IkappaBalphaM inhibited in vitro and in vivo expression of vascular endothelial
      growth factor (VEGF) and interleukin 8 (IL-8). Human glioma xenografts treated
      with IkappaBalphaM gene transfer exhibited significantly decreased angiogenesis
      both in an orthotopic and in an ectopic model. The decreased expression of VEGF
      and IL-8 directly correlated with decreased tumorigenicity, and tumor
      vascularization. Taken in combination, these results provide strong evidence of
      IkappaBalphaM's role in regulating glioma angiogenesis even in the presence of
      constitutive EGFR activation.

PMID- 15494124
TI  - Neuroprotection by D-securinine against neurotoxicity induced by beta-amyloid (25
      35).
AB  - The effects of (+) securinine on behavior and morphological changes after
      intracerebral ventricle injection of beta-amyloid (25-35) (Abeta(25-35)) in rats
      were investigated. A single high dose of Abeta(25-35) could impair the spatial
      cognitive function. The latency of locating the platform was longer in the model
      group than in the sham-operated group. While chronic administration of D
      securinine (40 mg kg(-1)) could significantly shorten the latency. After Morris
      water maze, the activity of choline acetyltransferase (ChAT) and
      acetylcholinesterase (AchE) were detected. The results showed that D-securinine
      could decrease the AchE activity significantly and have no effect on ChAT.
      Meanwhile, immunohistochemistry analysis revealed that D-securinine could reduce
      the glial inflammatory responses induced by beta-amyloid protein. These results
      suggest that the effect of D-securinine in improving the cognitive deficits and
      neurodegeneration in betaAP(25-35)-treated rats may involve direct and indirect
      actions on targets. The GABA receptor plays a key role in these therapeutic
      effects and may be helpful in the treatment of Alzheimer's disease.

PMID- 15494125
TI  - Objectivation of cerebral effects with a new continuous electrical auricular
      stimulation technique for pain management.
AB  - AIMS: The electrical point stimulation system (P-STIM) reflects a new,
      miniaturized system for pain therapy through ear acupuncture. For this reason,
      ultrathin needles were applied at the ear. The needles stimulate the acupuncture
      areas at the ear using electrical impulses, which come from a little generator
      applied behind the acupunctured ear. METHODS: This study describes continuous,
      non-invasive measurements of near infrared spectroscopy (NIRS) and
      multidirectional transcranial Doppler sonography in two healthy females (aged 23
      and 27 years) during stimulation with P-STIM, for the first time. RESULTS: The
      results of the pilot measurements have shown that electrical point stimulation
      using the new electrical stimulation system on eye acupuncture points is able to
      modulate the mean blood flow velocity (vm) of the supratrochlear artery. These
      effects were present using a stimulation frequency of 100 Hz. A lower increase in
      vm was found in the middle cerebral artery. In addition, stimulus induced,
      quantifiable and reproducible alterations of the regional cerebral NIRS
      parameters were be detected. CONCLUSION: For the first time, P-Stim allows
      intermittent ear acupuncture stimulation for up to several days in combination
      with complete mobility for the patient.

PMID- 15494126
TI  - Choline determination based on the intrinsic and the extrinsic (chemically
      modified) fluorescence of choline oxidase.
AB  - This paper describes two methods for the fluorometric determination of choline in
      serum by its reaction with the enzyme choline oxidase (ChOx). The first method,
      is based on changes in the intrinsic fluorescence of the enzyme
      (lambda(excitation)=28 nm and lambda(emission)=336 nm). The second method follows
      changes in the fluorescence intensity of a chemical modificant bonded to the
      enzyme (ChOx-FS), with excitation and emission maxima at 492 and 516 nm,
      respectively. Both methods have a similar response range (from 5 x 10(-7) to 10(
      5) M or to 5 x 10(-5) M, depending on the analytical parameter) and precision
      (about 5%). The origin of the enzyme fluorescence changes has been elucidated and
      a mathematical model explaining the analytical signal is presented. This model
      can be applied to other enzymatic reactions based on flavin-containing enzymes
      and enables prediction of the sensitivity of new methods based on the Km values.
      Both methods have been applied to choline determination in synthetic serum
      samples. Moreover, the use of ChOx-FS avoids sample pretreatment.

PMID- 15494127
TI  - Analysis of GAA/TTC DNA triplexes using nuclear magnetic resonance and
      electrospray ionization mass spectrometry.
AB  - The formation of a GAA/TTC DNA triplex has been implicated in Friedreich's
      ataxia. The destabilization of GAA/TTC DNA triplexes either by pH or by binding
      to appropriate ligands was analyzed by nuclear magnetic resonance (NMR) and
      positive-ion electrospray mass spectrometry. The triplexes and duplexes were
      identified by changes in the NMR chemical shifts of H8, H1, H4, 15N7, and 15N4.
      The lowest pH at which the duplex is detectable depends upon the overall
      stability and the relative number of Hoogsteen C composite function G to T
      composite function A basepairs. A melting pH (pHm) of 7.6 was observed for the
      destabilization of the (GAA)2T4(TTC)2T4(CTT)2 triplex to the corresponding Watson
      Crick duplex and the T4(CTT)2 overhang. The mass spectrometric analyses of
      (TTC)6.(GAA)6 composite function(TTC)6 triplex detected ions due to both triplex
      and single-stranded oligonucleotides under acidic conditions. The triplex ions
      disappeared completely at alkaline pH. Duplex and single strands were detectable
      only at neutral and alkaline pH values. Mass spectrometric analyses also showed
      that minor groove-binding ligands berenil, netropsin, and distamycin and the
      intercalating ligand acridine orange destabilize the (TTC)6.(GAA)6 composite
      function (TTC)6 triplex. These NMR and mass spectrometric methods may function as
      screening assays for the discovery of agents that destabilize GAA/TTC triplexes
      and as general methods for the characterization of structure, dynamics, and
      stability of DNA and DNA-ligand complexes.

PMID- 15494128
TI  - Measurement of lysosomal glucocerebrosidase activity in mouse liver using a
      fluorescence-activated cell sorter assay.
AB  - Lysosomal acid beta-glucocerebrosidase hydrolyzes glucocerebroside to glucose
      ceramide. Patients diagnosed with Gaucher disease, however, lack this enzyme,
      leading to the accumulation of glucocerebroside in tissue macrophages within
      multiple organs. Such patients can receive enzyme replacement therapy during
      which a human placental-derived or recombinant form of acid beta
      glucocerebrosidase is targeted to the macrophages. As part of evaluating the
      effectiveness of such therapies, currently available methodologies for measuring
      acid beta-glucocerebrosidase activity are primarily conducted in cultured cell
      lines or tissue culture. However, these in vitro assays are limited by their
      ability to evaluate the efficacy of in vivo acid beta-glucocerebrosidase
      replacement therapy in animal models. In particular, there is an unmet need to
      simultaneously define cellular localization and evaluate enzyme activity
      following treatment in vivo. In addition, results of commonly used fluorescent
      based assays for enzyme activity are difficult to compare day to day and/or
      across laboratories due to the variability inherent in flow cytometric
      measurement. In this article, we describe a reproducible and consistent
      quantitative method for the combined measurement of fluorescein intensity from
      enzyme-substrate conversion and cell localization by phenotype-specific
      phycoerythrin-antibody staining. Following infusion of recombinant human acid
      beta-glucocerebrosidase in mice, nonparenchymal cells are prepared from the
      livers of treated and control animals. Acid beta-glucocerebrosidase activity is
      measured in molecules of equivalent soluble fluorophore units within Kupffer cell
      populations as defined by phenotype-specific monoclonal antibodies. This assay
      should be applicable to investigations of other Gaucher disease treatments in
      both human and animal models.

PMID- 15494129
TI  - An assay of mammalian cell micropermeabilization based on measurements of
      cellular lactate production.
AB  - A method for the quantitative assay of mammalian cell micropermeabilization is
      described. The method is based on the permeabilization-induced loss of endogenous
      glycolytic cofactors and consequent discontinuation of cellular lactate
      production. Advantages of the method include sensitivity and precision similar to
      that of micropermeabilization assays based on the release of 86Rb+ from preloaded
      cells, avoidance of radioactivity, and simplicity of the measurements and
      equipment required.

PMID- 15494130
TI  - Simultaneous HPLC analysis of 8-hydroxydeoxyguanosine and 7-methylguanine in
      urine from humans and rodents.
AB  - With a recently developed high-performance liquid chromatography (HPLC) method
      based on anion exchange chromatography, precise fraction collection, and reversed
      phase chromatography, the oxidative DNA damage marker 8-hydroxydeoxyguanosine (8
      OH-dG) was measured in human urine samples. The HPLC analysis was further
      modified to measure 8-OH-dG in rat and mouse urine samples. In addition, the
      urinary RNA degradation product 7-methylguanine (m7Gua) was analyzed
      simultaneously. The correlation coefficient (r) for the correlation between
      urinary creatinine and m7Gua was 0.9 for rats and 0.8 for humans and mice. Levels
      of 8-OH-dG in relation to urinary creatinine were compared and found to be
      similar for humans and rats and twice as high for mice. Urinary levels of m7Gua,
      as normalized to creatinine, were several-fold higher in rodents as compared with
      human levels, thereby correlating with the higher resting metabolic rate of
      rodents. The presented results show that 8-OH-dG and m7Gua can be analyzed
      simultaneously and reliably in urine from humans and rodents. In addition, m7Gua
      may be used as a reliable marker instead of creatinine for the normalization of 8
      OH-dG in urine from rats and mice and also may be used in addition to
      normalization with creatinine in measurements of 8-OH-dG in human urine samples.

PMID- 15494131
TI  - Characterization of ionizing radiation-induced ring chromosomes by atomic force
      microscopy.
AB  - We applied atomic force microscopy (AFM) to the structural analysis of radiation
      induced ring chromosomes. Constrictions observed on the metaphase ring chromosome
      were found to correspond to the centromere regions of the ring chromosome in
      comparison with the AFM image of the centromere of rod chromosomes and with the
      fluorescence in situ hybridization (FISH) technique. Section analysis by AFM
      revealed that some ring-like chromosome fragments and ring-like chromatid
      fragments were thicker than standard chromosomes or chromatids, suggesting that
      they were ring chromosomes viewed edge on. Topographic analysis by AFM makes it
      possible to distinguish a ring viewed edge on that is difficult to recognize as a
      ring by light microscopy and to discriminate between a centric ring chromosome
      and an acentric ring chromosome using the same slides prepared for light
      microscopy.

PMID- 15494132
TI  - Functionalized nanocrystal-tagged fluorescent polymer beads: synthesis,
      physicochemical characterization, and immunolabeling application.
AB  - A methodology for incorporating solubilized CdSe/ZnS core/shell nanocrystals
      (NCs) into functionalized carboxylated polystyrene latexes 0.3-1 microm in
      diameter via a swelling procedure was developed and used for the production of
      homogeneous, highly fluorescent polymeric beads (HFPBs), which were found to be
      comparable in brightness to standard polymeric microspheres doped with organic
      fluorophores and more photostable than the latter by more than 50 times
      (Fluoresbrite yellow-orange microspheres were used as an example). The three
      dimensional (3D) confocal analysis of individual 1-microm HFPB demonstrated that
      the beads were doped with the NCs almost homogeneously. HFPBs 0.3 microm in
      diameter were conjugated with anti-mouse polyvalent immunoglobulins and used for
      immunofluorescent detection of p-glycoprotein, a mediator of the multidrug
      resistance phenotype, overexpressed in the membrane of MCF7r breast
      adenocarcinoma cells. The photostability of NCs-tagged HFPBs offers obvious
      advantages for the reconstruction of 3D confocal fluorescence images of antigen
      distribution, and their exceptionally high brightness combined with
      photostability permits the detection of a single antigen molecule using a
      standard epifluorescence microscope.

PMID- 15494133
TI  - Quantification of the major urinary metabolite of PGE2 by a liquid
      chromatographic/mass spectrometric assay: determination of cyclooxygenase
      specific PGE2 synthesis in healthy humans and those with lung cancer.
AB  - Prostaglandin (PG)E2 is a major cyclooxygenase (COX) product that is important in
      human physiology and pathophysiology. Quantification of systemic PG production in
      humans is best assessed by measuring excreted urinary metabolites. Accurate and
      easy-to-perform assays to quantify the major urinary metabolite of PGE2, 11alpha
      hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (PGE-M), do not
      exist. We now report the development of a robust and facile method to measure
      urinary PGE-M excretion in humans using stable isotope dilution techniques
      employing liquid chromatography/tandem mass spectrometry (LC/MS/MS).
      Concentrations of the metabolite in urine from healthy humans are nearly twofold
      greater in men than in women (10.4+/-1.5 vs. 6.0+/-0.7 ng/mg creatinine). Levels
      of PGE-M in healthy humans are suppressed significantly not only by the
      nonselective COX inhibitor ibuprofen but also by the COX-2 selective inhibitor
      rofecoxib, suggesting that the majority of PGE2 formed in vivo is derived from
      COX-2. Increased COX-2 expression and increased PGE2 production are associated
      with malignancy. Levels of PGE-M were found to be greatly increased in humans
      with unresectable non-small cell cancer of the lung, and this increase is
      dramatically reduced by administration of the COX-2 inhibitor celecoxib, implying
      that COX-2 contributes significantly to the overproduction of PGE2. In summary,
      quantification of PGE-M using LC/MS/MS provides a facile and accurate method to
      assess PGE2 formation in human physiological and pathophysiological processes.

PMID- 15494134
TI  - Simultaneous detection of variable number tandem repeats, single nucleotide
      polymorphisms, and allelic imbalance in the thymidylate synthase gene enhancer
      region using denaturing high-performance liquid chromatography.
AB  - Polymorphisms in the thymidylate synthase enhancer region (TSER) have been
      reported to be associated with alterations in thymidylate synthase (TS) mRNA
      protein levels. The TSER is characterized by the presence of variable double (2R)
      and triple (3R) number tandem repeats (VNTRs). In addition to VNTRs, single
      nucleotide polymorphisms (SNPs) and allelic imbalance (AI), including loss of
      heterozygosity (LOH), have recently been associated with response to 5
      fluorouracil (5-FU)-based chemotherapy. The aim of the current study was to
      develop a specific denaturing high-performance liquid chromatography (DHPLC)
      method for the rapid detection of these variations in the TSER in clinical
      samples. DHPLC analysis was validated in parallel with agarose gel
      electrophoresis (AGE), enzyme digestion, and quantitative reverse transcription
      polymerase chain reaction (Q-RT-PCR). The optimized DHPLC method resolved 100% of
      the known TSER variations, differentiated between homozygous and heterozygous
      genotypes, and allowed the qualitative and quantitative detection of AI,
      including LOH, in tumor samples. This DHPLC method was developed to permit the
      rapid, sensitive, and accurate identification of the TSER genotype (VNTRs, SNPs,
      and AI) in clinical protocols where response to flouropyrimidines may be
      correlated with TSER polymorphisms.

PMID- 15494135
TI  - A glucose biosensor based on chitosan-glucose oxidase-gold nanoparticles
      biocomposite formed by one-step electrodeposition.
AB  - An amperometric biosensor for the quantitative measurement of glucose is
      reported. The biosensor is based on a biocomposite that is homogeneous and easily
      prepared. This biocomposite is made of chitosan hydrogel, glucose oxidase, and
      gold nanoparticles by a direct and facile electrochemical deposition method under
      enzyme-friendly conditions. The resulting biocomposite provided a shelter for the
      enzyme to retain its bioactivity at considerably extreme conditions, and the
      decorated gold nanoparticles in the biocomposite offer excellent affinity to
      enzyme. The biosensor exhibited a rapid response (within 7s) and a linear
      calibration range from 5.0 microM to 2.4 mM with a detection limit of 2.7 microM
      for the detection of glucose. The combination of gold nanoparticles affinity and
      the promising feature of the biocomposite with the onestep nonmanual technique
      favor the sensitive determination of glucose with improved analytical
      capabilities.

PMID- 15494136
TI  - Complexities in horseradish peroxidase-catalyzed oxidation of
      dihydroxyphenoxazine derivatives: appropriate ranges for pH values and hydrogen
      peroxide concentrations in quantitative analysis.
AB  - The highly sensitive, convenient fluorescence assay, based on the oxidation of
      nonfluorescent 10-acetyl-3,7-dihydroxyphenoxazine (Amplex Red) to highly
      fluorescent resorufin, is becoming increasingly popular for hydrogen peroxide
      quantitation. Yet, the intricacies of the horseradish peroxidase-catalyzed
      oxidation of the reductant substrate Amplex Red by hydrogen peroxide and the
      resulting resorufin could complicate the assay design and data interpretation. In
      particular, substrate inhibition and enzyme inactivation at higher hydrogen
      peroxide concentrations were known to affect the enzyme kinetics and end-point
      fluorescence. In addition, here we report the spontaneous transformation of
      resorufin to less or nonfluorescent product(s) in the absence of hydrogen
      peroxide and horseradish peroxidase. This spontaneous decay of resorufin
      fluorescence is most prominent in the pH range 6.2-7.7, likely due to general
      base-catalyzed de-N-acetylation and polymerization of resorufin. From a practical
      point of view, precautions for properly designing assays for hydrogen peroxide or
      characterizing hydrogen peroxide-generating systems are discussed based on the
      spontaneous transformation of resorufin to less fluorescent compound(s),
      substrate inhibition and enzyme inactivation at higher (>100 microM) hydrogen
      peroxide concentrations, and enzymatic oxidation of resorufin to nonfluorescent
      resazurin.

PMID- 15494137
TI  - Determination of proteins with fullerol by a resonance light scattering
      technique.
AB  - Fullerol has been synthesized through the reaction of fullerene C60 with NaOH in
      aqueous solution by means of ultrasonic agitation and characterized by infrared
      and 1H-nuclear magnetic resonance spectroscopy. The fullerol obtained shows good
      solubility and excellent stability in water. A weak resonance light scattering
      (RLS) spectrum of fullerol was observed in aqueous solution. However, the
      intensity of the RLS signal could be enhanced in the presence of proteins,
      including bovine serum albumin (BSA), human serum albumin (HSA), pepsin (Pep),
      and lysozyme (Lys). Based on the enhancement of the RLS, a sensitive method for
      the determination of proteins has been established. The quantitative conditions
      were considered with regard to the effects of the pH, the ion strength, and the
      concentration of the fullerol. Under the optimum conditions, the intensity of the
      RLS was proportional to the concentration of proteins with the limits of
      detection of 9.7, 10.9, 57.4, and 8.5 ng mL(-1) for BSA, HSA, Pep, and Lys,
      respectively. Almost no interference can be observed from some amino acids,
      nucleic acids, and most of the metal ions. The model samples and human serum
      samples were determined satisfactorily with the proposed method.

PMID- 15494138
TI  - Metal-enhanced fluorescence immunoassays using total internal reflection and
      silver island-coated surfaces.
AB  - We present a generic immunoassay platform that uses enhanced total internal
      reflection fluorescence in the proximity of silver island films (SIFs), a surface
      coating consisting of metal (silver) particles. This platform is used with a
      model immunoassay where a protein antigen, rabbit immunoglobulin G, was
      immobilized on the SIF-coated glass surface. The signal from a fluorescent dye
      labeled anti-rabbit antibody binding to the surface antigen was detected;
      different color dyes have been tested. Close placement of the fluorophore to
      surface-bound silver nanostructures results in dramatic signal enhancement (up to
      40-fold) on the SIFs as compared with the glass slides. Use of the total internal
      reflection mode of excitation has significant advantages (over classic front-face
      excitation) for practical assay development. The limited evanescent wave
      excitation volume makes it possible to minimize the background signal and use the
      immunoassay with no need for any washing steps.

PMID- 15494139
TI  - In-gel precipitation of enzymatically released phosphate.
AB  - The phosphate precipitation reaction using ammonium molybdate and triethylamine
      under low pH has been applied to gel-based assays for detecting phosphate
      releasing enzymes. The sensitivity of the assay is 10 pmol Pi/mm2 of 1.5-mm-thick
      gel. The assay is applicable to enzymes with a wide range of optimal pH, from
      acid (pH 4.5) to alkaline phosphatase (pH 9.7), and to enzymes that use acid
      labile substrates such as apyrase and glutamine synthetase. Using a negative
      staining approach, maltose phosphorylase, a phosphate-consuming enzyme, can also
      be detected. The assay was used to detect glutamine synthetase isoforms,
      separated by nondenaturing polyacrylamide gel electrophoresis from crude maize
      extracts. For downstream applications such as staining gels for proteins, the
      gels with precipitate should be incubated in 10 mM dithiothreitol or beta
      mercaptoethanol until the precipitate is dissolved and then thoroughly washed in
      water. In comparison to calcium phosphate precipitation or the phosphomolybdate
      malachite green method, this method is more sensitive. It is a very simple,
      rapid, versatile, reproducible, and inexpensive method that could be a useful
      tool in enzymological studies.

PMID- 15494140
TI  - Partial specific volume and solvent interactions of amphipol A8-35.
AB  - Amphipols are small amphiphilic polymers that can stabilize and keep soluble
      membrane proteins in aqueous solutions in the absence of detergent. A
      prerequisite to solution studies of membrane protein/amphipol complexes is the
      determination of the partial specific volume v2 and effective charge z of the
      polymer. The ratio (R) of the buoyant molar masses of particles in D2O and H2O
      solutions, obtained from sedimentation velocity (sH/sD method) and sedimentation
      equilibrium experiments, and their contrast match point (CMP), determined in
      small-angle neutron scattering experiments, depend on v2 and z. When z is known,
      v2 can be estimated from R with a good accuracy as long as v2 is close to 1. The
      effects of labile H/D exchange and of polyelectrolyte counter-ion dissociation in
      general cannot be neglected. The accuracy, advantages, and limits of the sH/sD
      method have been studied in details using model macromolecules (DNA, protein, and
      polysaccharide). The sH/sD method appears particularly advantageous for the study
      of heterogeneous samples. Measurements of density, sD/sH buoyant molar masses in
      H2O, D2O, and D2(18)O, and CMP of hydrogenated and partially deuterated A8-35, a
      polyacrylate-based amphipol containing 35 underivatized carboxylates per 100
      monomers, led to a consistent description of its buoyancy and charge properties.

PMID- 15494141
TI  - A ready-to-use fluorimetric biosensor for superoxide radical using superoxide
      dismutase and peroxidase immobilized in sol-gel glasses.
AB  - In this work, a highly sensitive fluorescent biosensor for quantitative
      superoxide radical detection, based on the coupled reaction superoxide dismutase
      peroxidase enzymes and the use of the probe Amplex red, is described. Superoxide
      anion radical was produced via oxidation of xanthine by xanthine oxidase.
      Dismutation of superoxide was catalyzed by superoxide dismutase, generating
      hydrogen peroxide, which reacted stoichiometrically with the nonfluorescent
      Amplex red, in the presence of peroxidase, yielding the red-fluorescent oxidation
      product resorufin. The coupled superoxide dismutase-peroxidase system was
      immobilized in a single sol-gel matrix. The enzymatic activity of the
      encapsulated superoxide dismutase-peroxidase system was nearly identical to that
      of one of the soluble enzymes, indicating that sol-gel encapsulation preserved
      the hierarchy of the enzyme's activity. Specificity and reusability of the
      encapsulated system for up to four cycles were also demonstrated. The fluorescent
      biosensor was able to detect concentrations of superoxide as low as 20 nM in
      phospholipid model membranes composed of saturated or unsaturated phospholipids.
      These facts make this biosensor a simple, reliable, and highly sensitive method
      with a potential use in biological systems, food, and drinks.

PMID- 15494142
TI  - A cell-based beta-lactamase reporter gene assay for the identification of
      inhibitors of hepatitis C virus replication.
AB  - This report describes the development, optimization, and implementation of a cell
      based assay for high-throughput screening (HTS) to identify inhibitors to
      hepatitis C virus (HCV) replication. The assay is based on a HCV subgenomic RNA
      replicon that expresses beta-lactamase as a reporter for viral replication in
      enhanced Huh-7 cells. The drug targets in this assay are viral and cellular
      enzymes required for HCV replication, which are monitored by fluorescence
      resonance energy transfer using cell-permeable CCF4-AM as a beta-lactamase
      substrate. Digital image processing was used to visualize cells that harbor viral
      RNA and to optimize key assay development parameters such as transfection and
      culturing conditions to obtain a cell line which produced a robust assay window.
      Formatting the assay for compound screening was problematic due to small signal
      to-background ratio and reduced potency to known HCV inhibitors. These technical
      difficulties were solved by using clavulanic acid, an irreversible inhibitor of
      beta-lactamase, to eliminate residual beta-lactamase activity after HCV
      replication was terminated, thus resulting in an improved assay window. HTS was
      carried out in 384-well microplate format, and the signal-to-background ratio and
      Z factor for the assay plates during the screen were approximately 13-fold and
      0.5, respectively.

PMID- 15494143
TI  - Toward multiplexing the application of solvent accessibility probes for the
      investigation of RNA three-dimensional structures by electrospray ionization
      Fourier transform mass spectrometry.
AB  - Multiple solvent accessibility probes can be applied simultaneously to
      investigate the three-dimensional structure of complex RNA substrates when
      electrospray ionization-Fourier transform mass spectrometry (ESI-FTMS) is
      employed in place of polyacrylamide gel electrophoresis (PAGE). We show that
      classic chemical probes, such as dimethylsulfate, kethoxal, and 1-cyclohexyl-3-(2
      morpholinoethyl)carbodiimide metho-p-toluenesulfonate, can be combined in probing
      mixtures designed to assess the full spectrum of base pairing and steric
      protection for the most abundant ribonucleotides included in RNA. After probe
      independent hydrolysis of the alkylated substrate, the mixture of oligonucleotide
      products is mass mapped by ESI-FTMS analysis, which enables the unambiguous
      identification of probed bases from the unique mass signatures provided by the
      different chemical modifiers. In this bottom-up approach, any theoretical limit
      to the size of the possible target RNA will be determined by the effectiveness of
      the hydrolysis procedure rather than by the performance of the detection
      technique. Control experiments performed on the stem-loop 4 of human
      immunodeficiency virus type 1 have shown no adverse interactions between the
      reagents combined in the probing cocktails. No significant discrepancies between
      the alkylation patterns offered by the cocktails and the individual reagents
      could be detected, indicating that multiplexing the probe application does not
      necessarily lead to structural distortion but provides valid data on base
      accessibility and protection. To demonstrate the ruggedness of this approach,
      optimized cocktails were finally employed to assess the stability of the folded
      structure of mouse mammary tumor virus pseudoknot in the presence of different
      amounts of Mg2+. Multiplexing the probe application constitutes an essential step
      toward high-throughput applications, which will take advantage of a strategy that
      maximizes the information attainable from a single experiment, while minimizing
      time and sample consumption over PAGE-based methods.

PMID- 15494144
TI  - Real time analysis of intact organelles using surface plasmon resonance.
AB  - Membrane proteins remain refractory to standard protein chip analysis. They are
      typically expressed at low densities in distinct subcellular compartments, their
      biological activity can depend on assembly into macromolecular complexes in a
      specific lipid environment. We report here a real-time, label-free method to
      analyze membrane proteins inserted in isolated native synaptic vesicles. Using
      surface plasmon resonance-based biomolecular interaction analysis (Biacore),
      organelle capture from minute quantities of 10,000 g brain supernatant (1-10
      microg) was monitored. Immunological and morphological characterization indicated
      that pure intact synaptic vesicles were immobilized on sensor chips. Vesicle
      chips were stable for days, allowing repetitive use with multiple analytes. This
      method provides an efficient way in which to characterize organelle membrane
      components in their native context. Organelle chips allow a broad range of
      measurements, including interactions of exogenous ligands with the organelle
      surface (kinetics, Kd), and protein profiling.

PMID- 15494145
TI  - Simultaneous assay of DNA and RNA targets in the whole blood using novel
      isolation procedure and molecular colony amplification.
AB  - A universal procedure that permits the whole human blood to be tested for the
      presence of single molecules of DNA and RNA targets is described. The procedure
      includes a novel protocol for the isolation of total nucleic acids from the
      guanidinium thiocyanate lysate of unfractionated blood in which, prior to
      phenol/chloroform extraction, the sample is deproteinized by precipitation with
      isopropanol. The procedure results in a nearly 100% yield of DNA and RNA,
      preserves the integrity of RNA, and removes any polymerase chain reaction (PCR)
      inhibitors. Following reverse transcription (RT), target molecules are counted
      after having been amplified as molecular colonies by carrying out PCR in a
      polyacrylamide gel. The entire procedure was checked by assaying viral DNA and
      RNA in 100-microl aliquots of the whole blood and was found to be capable of
      detecting 100% molecules of DNA target and 50% molecules of RNA target.
      Unexpectedly, nucleic acids at relatively high concentrations (1 ng/microl) were
      found to selectively inhibit the RT activity of Thermus thermophilus DNA
      polymerase without affecting its DNA-dependent polymerization activity. It
      follows that the popular single-enzyme RT-PCR format, in which this DNA
      polymerase serves for both RT and PCR, is not appropriate for assaying rare RNA
      targets.

PMID- 15494146
TI  - Kinetics of an enzyme-catalyzed reaction measured by electrospray ionization mass
      spectrometry using a simple rapid mixing attachment.
AB  - Mass spectrometry offers a potential means of measuring virtually all enzyme
      catalyzed reactions by simultaneously measuring the concentrations of substrates,
      products, and intermediates where there are differences in mass between them. To
      perform these measurements the reaction mixture must be aged for different times
      and then ionized. Electrospray ionization mass spectrometry provides the most
      direct means of measuring these reactions. Here we describe a simple reaction
      mixing and ageing attachment for an electrospray ionization mass spectrometer,
      built from commercially available components. We have employed this device to
      measure the kinetics of a model reaction, namely the hydrolysis of N2
      (carbobenzyloxy)-L-lysine-p-nitrophenyl ester-catalyzed by trypsin. In this way
      we were able to measure the kinetics of substrate depletion, product formation,
      and changes in both free enzyme and acyl-enzyme intermediate concentration in the
      approach to steady state. With this device we were able to measure reaction times
      down to about 640 ms.

PMID- 15494147
TI  - Identification and quantitation of benzo[a]pyrene-derived DNA adducts formed at
      low adduction level in mice lung tissue.
AB  - The two major metabolic pathways of benzo[a]pyrene (BP) that lead to DNA lesions
      are monooxygenation that results in diolepoxides (BPDE) and one-electron
      oxidation that yields a BP radical cation. These pathways result in formation of
      stable and depurinating DNA adducts, respectively. Most in vivo animal studies
      with BP, however, have employed dosage/DNA adduct levels several orders of
      magnitude higher than the DNA damage level expected from environmentally relevant
      exposures. Presented are results of experiments in which A/J strain mice were
      intraperitoneally exposed to 50-microg/g doses of BP. It is shown that non-line
      narrowed fluorescence and fluorescence line-narrowing spectroscopies possess the
      selectivity and sensitivity to distinguish between helix-external, base-stacked,
      and intercalated conformations of DNA-BPDE adducts formed in lung tissue.
      Concentrations measured by 32P postlabeling 2 and 3 days after intraperitoneal
      injection were 420-430 and 600-830 amol BPDE-type adducts per microg DNA. The
      external and base-stacked conformations are attributed mainly to (+)-trans-anti
      BPDE-N2dG and the intercalated conformations to (+)-cis-anti adducts. A stable
      adduct derived from 9-OH-BP-4,5-epoxide was also detected at a concentration
      about a factor of 10 lower than the above concentrations. The DNA supernatants
      were analyzed for the presence of depurinating BP-derived adducts by capillary
      electrophoresis laser-induced fluorescence and high-performance liquid
      chromatography mass spectrometry.

PMID- 15494148
TI  - Immobilized DNA-binding assay, an approach for in vitro DNA-binding assay.

PMID- 15494149
TI  - Quantifying trimethylamine and trimethylamine-N-oxide in human plasma:
      interference from endogenous quaternary ammonium compounds.

PMID- 15494150
TI  - Chloride analysis using 3,3',5,5'-tetramethylbenzidine and chloroperoxidase.

PMID- 15494151
TI  - Dexamethasone inhibits proliferation of adult hippocampal neurogenesis in vivo
      and in vitro.
AB  - Activation of glucocorticoid receptor (GR) induces a reduction of adult
      hippocampal neurogenesis found in dentate gyrus (DG). However, the nature of
      specific effects by glucocorticoid in hippocampal neurogenesis is not known. In
      this report, we show differential effects of dexamethasone (DEX), a
      glucocorticoid receptor agonist, on proliferation and functional differentiation
      of adult hippocampal progenitor cells in DG. Two-month-old adult rats received
      daily injections of DEX for 9 days and were sacrificed 12 h and 28 days after the
      ninth injection. Proliferation assays showed that DEX inhibited proliferation of
      neural progenitor cells and the inhibitory effects of DEX was not detected 28
      days after recovery. Functional differentiation studies using B-cell lymphoma
      protein-2 (Bcl-2), brain-derived neurotrophic factor (BDNF), p-ERK, and neuronal
      nuclear protein (NeuN) antibodies revealed that the expressions of Bcl-2 and BDNF
      were not significantly different between control and DEX-treated rats. In
      contrast, however, the activation of extracellular signal-regulated kinase (ERK)
      was downregulated 12 h, but not 28 days, after the DEX treatment. When adult
      hippocampal progenitor cell cultures were treated with subchronic DEX,
      proliferation of the progenitor cells was suppressed. Taken these in vitro and in
      vivo results together, it is concluded that glucocorticoid receptor activation
      blocks only proliferation, but not differentiation, in hippocampal neurogenesis.

PMID- 15494152
TI  - nNOS expression following inferior alveolar nerve injury in the ferret.
AB  - Damage to the inferior alveolar nerve (IAN) may result in permanent painful
      dysaesthesia, and there is compelling evidence to suggest that ectopic activity
      from the injury site plays a crucial role in the initiation of this disorder. The
      aim of this study was to determine whether neuronal nitric oxide synthase (nNOS),
      a regulator of neuronal excitability, could be involved in the development of the
      abnormal activity. In seven ferrets, the left IAN was exposed and a retrograde
      tracer, fluorogold, was applied to the nerve for the identification of cell
      bodies in the trigeminal ganglion with axons in the IAN. In four animals, the
      nerve was sectioned distal to the injection site, and three served as controls.
      After 3 days, the animals were perfused with fixative, and the left and right
      IANs and trigeminal ganglia were processed using indirect immunofluorescence for
      nNOS. Image analysis was used to quantify the percentage area of staining (PAS)
      at the injury site. In the ganglia, counts were made of positively labelled cells
      in the fluorogold population. At the injury site, PAS was significantly greater
      in injured nerves than in either contralateral or control nerves, and
      contralateral PAS was elevated compared to control. In the ganglia, the
      proportion of nNOS-labelled cells was significantly reduced following injury.
      These results indicate a possible translocation of the nNOS protein from the cell
      body to the site of nerve injury, where it accumulates. Thus, nNOS could play a
      role in the development of ectopic activity at a site of trigeminal nerve injury.

PMID- 15494153
TI  - Experimental study on the regeneration of peripheral nerve gaps through a
      polyglycolic acid-collagen (PGA-collagen) tube.
AB  - We have developed a bioabsorbable polyglycolic acid (PGA) tube filled with
      collagen sponge (PGA-collagen tube) as a nerve connective guide, and compared its
      effectiveness with that of autograft in terms of nerve regeneration across a gap.
      The PGA-collagen tube was implanted into 24 beagle dogs across a 15-mm gap in the
      left peroneal nerve. The right peroneal nerve was reconstructed with the
      autograft harvested from the left side, as a control. After the surgery, the
      connective tissue extended from both cut ends in the PGA-collagen tube and
      connected again at the center. Pathologically, the collagen sponge in the tube
      provided adequate scaffolding for nerve tissue extension, and the nerve tissue
      reconnected within 3 weeks. Electrophysiologically, muscle-evoked potentials
      (MEPs) and compound nerve action potentials (CNAPs) were detected 18 days after
      the surgery. For up to 6 months postsurgery, CNAPs and somatosensory-evoked
      potentials (SEPs) on the PGA-collagen side had a shorter latency and larger peak
      voltage than those on the autograft side. The myelinated axons on the PGA side
      were larger in diameter than those on the autograft side. It is suggested that
      the PGA-collagen tube has the potential to be an effective alternative to
      conventional autografting for the repair of some peripheral nerve defects.

PMID- 15494154
TI  - Brain ischemic preconditioning is abolished by antioxidant drugs but does not up
      regulate superoxide dismutase and glutathion peroxidase.
AB  - The present work examined the hypothesis that brain ischemic tolerance induced by
      ischemic preconditioning (IPC) is triggered by an initial oxidative stress and is
      associated with an increase in antioxidant enzyme activities as one end-effector
      of the neuroprotection. Wistar rats were preconditioned by a single 3-min
      occlusion of the middle cerebral artery. After a various duration of reperfusion
      (30 min, 24, 72 or 168 h), rats were subjected to a 60-min focal ischemia and
      sacrificed 24 h later. Cerebral infarcts were significantly reduced when
      performed during the 24- to 72-h time window after IPC. The pretreatment with the
      protein synthesis inhibitor, cycloheximide (1 mg/kg, i.p., 30 min prior to IPC),
      completely suppressed the neuroprotection. The free radical scavenger,
      dimethylthiourea (DMTU; 300 mg/kg, i.p., 30 min prior to IPC) and the antioxidant
      ebselen (10 mg/kg, oral cramming, 2 h before and 12 h after IPC) also abolished
      the IPC-induced protection of the brain. Nevertheless, IPC did not induce any
      delayed changes in antioxidant enzyme (superoxide dismutase, glutathion
      peroxidase) activities nor in the neuronal expression of Mn and Cu/Zn superoxide
      dismutase. These results indicate that an initial oxidative stress could be
      involved as a trigger of IPC, while antioxidant enzymes do not play a key role as
      end-effectors in such a neuroprotection.

PMID- 15494155
TI  - Mechanisms involved in the blood-brain barrier increased permeability induced by
      Phoneutria nigriventer spider venom in rats.
AB  - We have recently demonstrated by electron microscopy, using lanthanum nitrate as
      an extracellular tracer, that the intravenous injection of Phoneutria nigriventer
      spider venom (PNV) induces blood-brain barrier (BBB) breakdown in rat
      hippocampus. One and nine days after PNV injection, tracer was found in pinocytic
      vesicles crossing the endothelium and in the interendothelial cleft, suggesting
      that BBB breakdown had occurred through enhanced transendothelial transport
      and/or tight-junction opening. In the present work, we investigated the
      mechanisms by which PNV (850 microg/kg, i.v.) increased the hippocampal
      microvascular permeability in rats 24 h after the endovenous administration. The
      expression and phosphorylation of some tight- and adherens junctions-associated
      proteins in hippocampal homogenate and hippocampal microvessel homogenate were
      assessed by Western blotting and immunoprecipitation. The microtubule-dependent
      transcellular transport was also evaluated by quantitative ultrastructural
      methods in pretreated rats with colchicine (0.5 mg/kg, i.p.), prior to PNV
      injection. Western blots showed no significant increase in the expression of the
      tight junction-associated proteins ZO-1 and occludin or in the adherens junction
      associated beta-catenin after 24 h of PNV administration. Morphological study
      showed no alterations of the immunolabeling for occludin and ZO-1 in rat brain
      cryosection following PNV. In addition, no changes were observed in
      phosphotyrosine content of occludin and beta-catenin in PNV-treated rats compared
      with control animals. However, the disruption of microtubule-dependent
      transcellular transport by colchicine completely prevented (p<0.001) PNV-induced
      leakage of the BBB tracer. These findings indicate that the increased BBB
      permeability evoked by PNV in rats probably resulted from enhanced microtubule
      dependent transendothelial vesicular transport, with no substantial involvement
      of the paracellular barrier in the time interval studied.

PMID- 15494156
TI  - Nicotine increases in vivo blood-brain barrier permeability and alters cerebral
      microvascular tight junction protein distribution.
AB  - The blood-brain barrier (BBB) is critical to the health of the central nervous
      system. The BBB is formed primarily by the presence of tight junctions (TJ)
      between cerebral microvessel endothelial cells. In light of the known effects of
      nicotine on endothelial cell biology, the specific effects of nicotine on the in
      vivo BBB were examined. Using in situ brain perfusion, it was found that
      continuous administration of nicotine (4.5 mg free base x kg(-1) x day(-1)) for 1
      and 7 days led to increased permeability of the BBB to [14C]-sucrose without
      significant changes in its initial volume of distribution. The expression and
      distribution of the TJ-associated proteins actin, occludin, claudin-1, -3, and 
      5, and ZO-1 and -2 were analyzed by Western blot and immunofluorescence
      microscopy. Though no changes in total protein expression were observed, nicotine
      treatment was associated with altered cellular distribution of ZO-1 and
      diminished junctional immunoreactivity of claudin-3. It is proposed that nicotine
      leads to changes in BBB permeability via the modulation of TJ proteins.

PMID- 15494157
TI  - Effects of ramelteon (TAK-375) on nocturnal sleep in freely moving monkeys.
AB  - We investigated the effects of (S)-N-[2-(1,6,7,8-tetrahydro-2H-indeno-[5,4]furan
      8-yl)ethyl]propionamide (ramelteon, TAK-375), a novel MT1/MT2 receptor agonist,
      on nocturnal sleep in freely moving monkeys and compared these results with those
      of melatonin and zolpidem. Treatment with ramelteon (0.03 and 0.3 mg/kg, p.o.)
      significantly shortened latency to sleep onset and significantly increased total
      duration of sleep. Treatment with melatonin (0.3, 1, and 3 mg/kg, p.o.) also
      decreased sleep latency, but the effect was weak; the only significant reduction
      was seen with the 0.3 mg/kg dose on latency to light sleep. Melatonin had no
      significant effects on the duration of sleep. Zolpidem had no significant effects
      on latency to sleep onset in this study at any dose (1, 3, 10, and 30 mg/kg,
      p.o.). The highest dose (30 mg/kg) of zolpidem had a tendency to increase slow
      wave sleep; however, it also induced apparent sedation and myorelaxation.
      Treatment with ramelteon and melatonin had no evident effect on the general
      behavior of the monkeys. Spectral analysis (fast Fourier transform, FFT) of both
      ramelteon and melatonin revealed sleep patterns that were indistinguishable from
      those of naturally occurring sleep. The EEG power spectra of zolpidem were
      qualitatively different from that of naturally occurring physiological sleep.
      Results of the present study support the investigation of ramelteon as a sleep
      promoting agent in humans.

PMID- 15494158
TI  - Sciatic nerve regeneration in mice and rats: recovery of sensory innervation is
      followed by a slowly retreating neuropathic pain-like syndrome.
AB  - Peripheral nerve regeneration has been studied extensively in the sciatic nerve
      crush model, at the level of both function and gene expression. The crush injury
      allows full recovery of sensory and motor function in about 3 weeks as assessed
      by the foot reflex withdrawal test and De Medinacelli walking patterns. We used
      the recently developed CatWalk paradigm to study walking patterns in more detail
      in mice and rats. We found that, following the recovery of sensory function, the
      animals developed a state of mechanical allodynia, which retreated slowly over
      time. The motor function, although fully recovered with the conventional methods,
      was revealed to be still impaired because the animals did not put weight on their
      previously injured paw. The development of neuropathic pain following successful
      sensory recovery has not been described before in crush-lesioned animals and may
      provide an important new parameter to assess full sensory recovery.

PMID- 15494159
TI  - Activation of programmed cell death markers in ventral horn motor neurons during
      early presymptomatic stages of amyotrophic lateral sclerosis in a transgenic
      mouse model.
AB  - The identification of the pathogenic mechanism of selective motor neuron (MN)
      death in amyotrophic lateral sclerosis (ALS) may lead to the development of new
      therapies to halt or slow the disease course. A novel, MN-specific, Fas-mediated
      programmed cell death (PCD) pathway has been reported in MNs which involves the
      activation of p38 MAP kinase (phospho-p38) and neuronal nitric oxide synthase
      (nNOS). PCD was found to be exacerbated in MNs expressing ALS-linked superoxide
      dismutase (SOD) mutations. Because this MN-specific pathway was investigated in
      vitro, we performed an in vivo study to evaluate its potential involvement in MN
      loss in the lumbar region of spinal cord of mutant SOD transgenic (G93A) mice.
      Compared to nontransgenic littermates, we found significant increases in the
      numbers of immunopositive ventral horn MNs of G93A mice as young as 60 days of
      age for several constituents of this putative PCD pathway, including phospho-p38,
      nNOS, phospho-ASK1 MAP kinase kinase, and active caspase-3. This study provides
      in vivo evidence of an MN-specific PCD pathway that may be a pathogenic mechanism
      of ALS and may be activated very early in the disease process, well before
      clinical symptoms are evident (200 days). These findings suggest that early
      diagnosis and therapeutic intervention may be critical for the successful
      treatment of the disease. These enzymes may provide new markers for earlier
      diagnosis of ALS and new molecular targets for therapeutic intervention.

PMID- 15494160
TI  - Temporary inactivation of the nucleus accumbens disrupts acquisition and
      expression of fear-potentiated startle in rats.
AB  - Recent research suggests that in addition to its prominent role in appetitive
      learning, the nucleus accumbens (NAC) may also be involved in fear conditioning.
      In the present study, we investigated whether temporary inactivation of the NAC,
      by injection of tetrodotoxin (TTX), affects acquisition and expression of
      conditioned fear, as measured by fear-potentiated startle (FPS). TTX injection
      into the NAC totally blocked acquisition and markedly decreased expression of
      conditioned fear to a discrete visual conditioned stimulus (CS). Interestingly,
      temporary inactivation of the NAC did not affect shock sensitization of startle,
      indicating that both the perception of the shock and short-term contextual
      conditioning was not affected by intra-accumbal TTX injection. Taken together,
      these results show that the NAC is crucial for acquisition and expression of long
      term conditioned fear, as measured by fear-potentiated startle, to discrete CSs,
      but not short-term conditioned fear to a context.

PMID- 15494161
TI  - Ultrastructure of the rostral ventral respiratory group neurons in the
      ventrolateral medulla of the rat.
AB  - The neurons in the ventrolateral medulla that project to the spinal cord are
      called the rostral ventral respiratory group (rVRG) because they activate spinal
      respiratory motor neurons. We retrogradely labeled rVRG neurons with Fluoro-Gold
      (FG) injections into the fourth cervical spinal cord segment to determine their
      distribution. The rostral half of the rVRG was located in the area ventral to the
      semicompact formation of the nucleus ambiguus (AmS). A cluster of the neurons
      moved dorsally and intermingled with the palatopharyngeal motor neurons at the
      caudal end of the AmS. The caudal half of the rVRG was located in the area
      including the loose formation of the nucleus ambiguus caudal to the AmS. We also
      labeled the rVRG neurons retrogradely with wheat germ agglutinin-horseradish
      peroxidase (WGA-HRP) to determine their ultrastructural characteristics. The
      neurons of the rVRG were medium to large (38.1 x 22.1 microm), oval or ellipsoid
      in shape, and had a dark cytoplasm containing numerous free ribosomes, rough
      endoplasmic reticulum (rER), mitochondria, Golgi apparatuses, lipofuscin granules
      and a round nucleus with an invaginated nuclear membrane. The average number of
      axosomatic terminals in a profile was 33.2. The number of axosomatic terminals
      containing round vesicles and making asymmetric synaptic contacts (Gray's type I)
      was almost equal to those containing pleomorphic vesicles and making symmetric
      synaptic contacts (Gray's type II). The axodendritic terminals were large (1.55
      microm), and about 60% of them were Gray's type I. The rVRG neurons have
      ultrastructural characteristics, which are different from the palatopharyngeal
      motor neurons or the prorpiobulbar neurons.

PMID- 15494162
TI  - Different ataxin-2 antibodies display different immunoreactive profiles.
AB  - We have developed a monoclonal antibody (4A7) directed against the C-terminus of
      the ataxin-2 protein that is involved in the polyglutamine neurodegenerative
      disorder spinocerebellar ataxia type 2. Comparison with other ataxin-2 antibodies
      showed that 4A7 specifically recognized ataxin-2. In contrast, a previously
      reported ataxin-2 antibody (15F6) did not appear to recognize full-length ataxin
      2 in our systems. Immunocytochemical and subcellular fractionation studies using
      4A7 confirmed previous reports that ataxin-2 is localized to both the cytoplasm
      and the trans-Golgi network in rat PC12 cells and rat brain tissue. In contrast,
      4A7 failed to label the trans-Golgi network in the three primate cell lines
      examined. Cytoplasmic ataxin-2 was not associated with mitochondria, lysosomes,
      endoplasmic reticulum, peroxisomes, proteasomes, clathrin-coated pits or
      vesicles, or F-actin. Ataxin-2 was found to be phosphorylated but not
      glycosylated, and exhibited an estimated half-life of not less than 21 h.
      Interestingly, another commercially available ataxin-2 antibody did not detect
      ataxin-2 localized to the trans-Golgi network. This antibody was also found to
      immunoprecipitate fewer proteins/protein partners than 4A7. Although cross
      reactivity of the 4A7 antibody with other protein(s) cannot be ruled out, it
      appears likely that the interaction of ataxin-2 with other cell components is
      dependent on both the host cell type and its subsequent subcellular localization.

PMID- 15494163
TI  - Mice deficient in the interferon type I receptor have reduced REM sleep and
      altered hypothalamic hypocretin, prolactin and 2',5'-oligoadenylate synthetase
      expression.
AB  - We report that mice with a targeted null mutation in the interferon type I
      receptor (IFN-RI), which cannot respond to such IFNs as IFNalpha and IFNbeta,
      have a 30% reduction in time spent in spontaneous rapid eye movement sleep (REMS)
      as a consequence of a reduced number of REMS episodes. Time spent in nonrapid eye
      movement sleep (NREMS) was essentially unaltered in IFN-RI knockouts (KOs)
      compared to 129 SvEv controls. Body temperature and locomotor activity were
      similar in both strains of mice. Hypothalamic expression of mRNAs for molecules
      previously linked to sleep-wake regulation and an IFN-inducible antiviral gene,
      2',5'-oligoadenylate synthetase 1a (OAS), were determined by real-time reverse
      transcriptase polymerase chain reaction (RT2-PCR). The level of hypocretin A mRNA
      was elevated in IFN-RI KO mice compared to 129 SvEv mice, while prolactin mRNA
      and OAS mRNA levels were suppressed. Vasoactive intestinal peptide (VIP) and
      corticotropin-releasing hormone (CRH) mRNA levels were unchanged relative to
      controls. Serum prolactin levels were similar in both strains. Results are
      consistent with the hypothesis that increased hypocretin and reduced prolactin in
      the hypothalamus of IFN-RI KO mice are responsible for their reduced REMS. In
      addition, the reduced OAS expression may result in modulation of prolactin
      receptor signaling and thus contribute to suppression of REMS.

PMID- 15494164
TI  - Ontogeny of feline temporal lobe epilepsy in amygdala-kindled kittens: an update.
AB  - This report describes amygdala-kindled seizure development and the post-kindling
      course in 58 cats (29 males and 29 females), including 40 preadolescents between
      2.5 and 6.5 months of age and 18 adults >1 year of age at the beginning of
      kindling. The results extend previous findings, as follows: (1) Youngest animals
      (<5.0 months, n=30) are far more likely than older kittens and adults to exhibit
      spontaneous epilepsy, indexed by seizures that occur >1 h after stimulus-evoked
      seizures. (2) The youngest animals also exhibit accelerated kindling rates and
      rapid post-kindling onset of multifocal spontaneous epilepsy with a catastrophic
      clinical course. The profile includes a variety of EEG and/or clinical seizure
      manifestations and a progressive increase in the number and density of convulsive
      seizure clusters. Behavioral sequelae accompany seizure clusters and can range
      from sensory or motor deficits (visual agnosia, sensory hypersensitivity, atonic
      episodes, restricted mobility) to social isolation and placidity. (3) Onset of
      spontaneous epilepsy with developmental deterioration is substantially enhanced
      by recurrent evoked seizures early in the post-kindling course. The post-kindling
      progression can be stopped or minimized by suspension of evoked seizure trials
      and/or by management of frequent spontaneous convulsions (>1 per hour) with
      anticonvulsants. (4) In older cats, many more evoked seizures are required to
      generate fewer spontaneous seizures with relatively innocuous behavioral
      disorders. The findings suggest a 'critical period' in kindled kittens for onset
      of spontaneous temporal lobe epilepsy with severe behavioral consequences and a
      favorable prognosis for the young following early detection and intervention.

PMID- 15494165
TI  - GABAA-5-HT1A receptor interaction in the mediobasal hypothalamus.
AB  - Both serotonin (5-HT) and gamma-aminobutyric acid (GABA) modulate female rat
      lordosis behavior and appear to interact in their control of the behavior. The
      current experiments were designed to investigate the interaction between these
      two neurotransmitters in sexually receptive female rats. Ovariectomized female
      rats, with bilateral cannulae directed toward the ventromedial nucleus of the
      hypothalamus (VMN), were hormonally primed with 10 microg estradiol benzoate and
      500 microg progesterone. Sexual behavior was examined after intracranial infusion
      with 200 ng (+/-)-8-hydroxy 2-(di-n-propylamino)tetralin (8-OH-DPAT), 25 ng (5
      aminomethyl-3-hydroxyisoxazole)hydrobromide (muscimol), 10 ng bicuculline or a
      combination of the drugs. As expected, 8-OH-DPAT reduced lordosis behavior and
      muscimol attenuated this inhibition in a bicuculline-sensitive manner. Muscimol
      alone also reduced lordosis behavior. These findings contrast with several
      reports that muscimol facilitates lordosis behavior of suboptimally hormonally
      primed female rats. The current outcome is discussed in terms of procedural
      differences between the present experiment and earlier studies. It is suggested
      that muscimol may enhance lordosis responding in suboptimally hormonally primed
      rats by activation of GABAA receptors located dorsal to the VMN. In contrast,
      activation of receptors located more ventrally within the mediobasal hypothalamus
      (MBH) may inhibit the behavior of rats that are already sexually receptive.

PMID- 15494167
TI  - Sex and repeated restraint stress interact to affect cat odor-induced defensive
      behavior in adult rats.
AB  - The overall objective of the present experiment was to assess sex differences in
      the effects of repeated restraint stress on fear-induced defensive behavior and
      general emotional behavior. Groups of male and female Long-Evans rats received
      either daily restraint stress (stressed) or daily brief handling (nonstressed)
      for 21 consecutive days. On days 22-25, a number of behavioral tests were
      administered concluding with a test of defensive behavior in response to a
      predatory odor. Stressed and nonstressed males and females were exposed to a
      piece of cat collar previously worn by a female domestic cat (cat odor) or a
      piece of collar never worn by a cat (control odor) in a familiar open field
      containing a hide barrier. Rats displayed pronounced defensive behavior
      (increased hiding and risk assessment) and decreased nondefensive behavior
      (grooming, rearing) in response to the cat odor. Nonstressed females exposed to
      cat odor displayed less risk assessment behavior relative to nonstressed males
      exposed to cat odor. Restraint stress had little effect on defensive behavior in
      male rats but significantly increased risk assessment behaviors in females.
      Behavior on the Porsolt forced swim test (a measure of depression-like behavior)
      and the open field test (a measure of anxiety-like behavior) was not affected by
      stress or sex. These findings indicate the utility of the predator odor paradigm
      in detecting subtle shifts in naturally occurring anxiety-like behaviors that may
      occur differentially in males and females.

PMID- 15494166
TI  - Glutamate transporters and metabotropic receptors regulate excitatory
      neurotransmission in the medial entorhinal cortex of the rat.
AB  - In layer III of the medial entorhinal cortex (mEC), a region that is especially
      prone to cell damage in Alzheimer's disease, schizophrenia and epilepsy, effects
      of blocking glutamate uptake on excitatory synaptic transmission were studied.
      Two competitive glutamate transporter antagonists, TBOA and tPDC, reduced the
      amplitude of pharmacologically isolated AMPAR and NMDAR mediated EPSPs/EPSCs
      without changing the time course of the events. This effect was mimicked by
      tACPD, an agonist of groups I and II metabotropic glutamate receptors (mGluRs).
      The competitive groups I and II mGluR antagonist MCPG blocked the depression of
      the EPSC amplitude induced by tACPD and also prevented the effect of either TBOA
      or tPDC. Furthermore, EGLU, which selectively antagonizes group II mGluRs,
      blocked the effect of tPDC and LY3414965, a specific group I mGluR antagonist,
      abolished the reduction of amplitude caused by TBOA. Additionally, application of
      TBOA increased the paired-pulse index, suggesting a presynaptic mechanism for the
      depression of EPSP/EPSC amplitude. The present data suggest that glutamate
      transporters and group I/II mGluRs regulate excitatory synaptic transmission in
      the mEC. Presynaptic mGluRs may limit excessive glutamate accumulation if uptake
      becomes compromised.

PMID- 15494168
TI  - Noradrenergic alpha-2 agonists have anxiolytic-like actions on stress-related
      behavior and mesoprefrontal dopamine biochemistry.
AB  - Clonidine (CLON), an alpha-2 agonist, has anxiolytic-like actions on the response
      of mesoprefrontal dopamine (DA) neurons to aversive stimuli in addition to some
      fear-related behavioral responses. We hypothesized that the anxiolytic-like
      actions of clonidine could be mimicked by stimulation of alpha-2 receptors on the
      mesoprefrontal dopamine neurons. Here, we test this hypothesis using clonidine or
      guanfacine (GFC), another alpha-2 agonist, in a model of aversive conditioning
      that selectively activates the mesoprefrontal dopamine neurons. One day prior to
      testing with drugs, rats were conditioned to fear a soft tone by pairing it with
      a footshock. During testing, the animals were subjected to the tones alone after
      drugs were administered systemically, or by local infusion into the regions
      containing the cell bodies and terminals of the mesoprefrontal dopamine neurons,
      namely, the ventral tegmental area (VTA) and the prelimbic (PL) cortex. Systemic
      administration of guanfacine blocked the increase in immobility in response to
      the conditioned tone and prevented the stress-associated increase in dopamine
      turnover in the prelimbic cortex. Systemic clonidine also prevented the stress
      associated increase in dopamine turnover but caused sedation preventing
      behavioral measures. Guanfacine was then used in all local injection studies. The
      local application of guanfacine into either the prelimbic cortex or the ventral
      tegmental area did not prevent the conditioned fear-induced increase in dopamine
      turnover or the increase in immobility in response to the conditioned tones. We
      conclude that the anxiolytic-like actions of alpha-2 agonists are not due to
      binding to alpha-2 receptors on the stress-sensitive mesoprefrontal dopamine
      neurons.

PMID- 15494169
TI  - Persistence of PAD and presynaptic inhibition of muscle spindle afferents after
      peripheral nerve crush.
AB  - Two to twelve weeks after crushing a muscle nerve, still before the damaged
      afferents reinnervate the muscle receptors, conditioning stimulation of group I
      fibers from flexor muscles depolarizes the damaged afferents [M. Enriquez, I.
      Jimenez, P. Rudomin, Changes in PAD patterns of group I muscle afferents after a
      peripheral nerve crush. Exp. Brain Res., 107 (1996), 405-420]. It is not known,
      however, if this primary afferent depolarization (PAD) is indeed related to
      presynaptic inhibition. We now show in the cat that 2-12 weeks after crushing the
      medial gastrocnemius nerve (MG), conditioning stimulation of group I fibers from
      flexors increases the excitability of the intraspinal terminals of both the
      intact lateral gastrocnemius plus soleus (LGS) and of the previously damaged MG
      fibers ending in the motor pool, because of PAD. The PAD is associated with the
      depression of the pre- and postsynaptic components of the extracellular field
      potentials (EFPs) evoked in the motor pool by stimulation of either the intact
      LGS or of the previously damaged MG nerves. These observations indicate, in
      contrast to what has been reported for crushed cutaneous afferents [K.W. Horch,
      J.W. Lisney, Changes in primary afferent depolarization of sensory neurones
      during peripheral nerve regeneration in the cat, J. Physiol., 313 (1981), 287
      299], that shortly after damaging their peripheral axons, the synaptic efficacy
      of group I spindle afferents remains under central control. Presynaptic
      inhibitory mechanisms could be utilized to adjust the central actions of muscle
      afferents not fully recovered from peripheral lesions.

PMID- 15494170
TI  - Renormalization of regional brain blood flow during prolonged mild hypoxic
      exposure in rats.
AB  - In this study, we measured regional brain blood flow (BF) in rats during hypoxic
      exposure. Our data show the hypoxia-induced brain blood flow increase returned to
      baseline within 1 week as blood hemoglobin increased. Because this return to
      baseline occurred before capillary angiogenesis, this result suggests that the
      mechanism for brain blood flow renormalization during prolonged hypoxia exposure
      is more likely related to the increased systemic arterial oxygen carrying
      capacity than to local tissue hypoxia that persists for at least 2 weeks.

PMID- 15494171
TI  - The effects of ebselen on [3H]glutamate uptake by synaptic vesicles from rat
      brain.
AB  - Ebselen is a selenium organic compound, which has been shown to be a
      neuroprotective agent in brain disorders involving glutamate receptors. However,
      the effects of ebselen on the functionality of the glutamatergic system are still
      poorly investigated. In this study, by using synaptic vesicle preparation, we
      investigated the effects of ebselen (0.3 to 10 microM) on (i) vesicular glutamate
      uptake, (ii) bafilomycin-sensitive H+ -ATPase activity, and (iii) proton gradient
      formation (DeltapH). Ebselen presented a dual effect on glutamate uptake: the 1
      microM concentration resulted in a 60% increase of the uptake, while the 10
      microM concentration resulted in 60% inhibition. We also observed that ebselen
      (10 microM) inhibited the H+ -ATPase activity and dissipated the DeltapH. The
      inhibitory effects of ebselen were prevented by dithiothreitol (DTT). These
      findings suggest that high concentrations of ebselen may oxidize the essential
      thiol groups of the H+ -ATPase, which in turn affect its activity and compromise
      the vesicular glutamate uptake, and consequently lead to an impairment of the
      neural homeostasis.

PMID- 15494172
TI  - Mechanism underlying inhibition of the capsaicin receptor-mediated current by
      pregnenolone sulfate in rat dorsal root ganglion neurons.
AB  - The effect of pregnenolone sulfate (PS) on the capsaicin receptor-mediated
      current was studied in acutely dissociated rat dorsal root ganglion neurons using
      the whole-cell voltage-clamp technique. PS acted extracellularly to inhibit the
      capsaicin-induced current in a not competitive but concentration-dependent
      manner, with an EC50 of 13 microM and a maximal inhibition of 65%. Furthermore,
      antagonism of the capsaicin response by PS is neither voltage- nor agonist
      dependent, indicating that PS did not act as an open-channel blocker. The
      inhibitory action of PS on the capsaicin-induced current may provide a basis for
      reducing capsaicin receptor-mediated nociception.

PMID- 15494173
TI  - Incorporating mating preferences into a host-parasite model.
AB  - Mating preferences are incorporated into a host-macroparasite system. Mating
      preferences of the host and/or parasite can affect the outcome of the host
      parasite relationship if certain genotypes of the host are more (or less)
      affected by the parasite induced death rate than others. Several examples
      illustrate the situations that can occur.

PMID- 15494174
TI  - Analytical and computational techniques for exogenous depolymerization of
      xenobiotic polymers.
AB  - We analyze a mathematical model for exogenous depolymerization of xenobiotic
      polymers. We derive a sufficient condition for the solvability of its inverse
      problem to determine degradation rates. We also introduce a numerical technique
      to solve the inverse problem with an example to show how our numerical technique
      is applied to gel permeation chromatography data of polyethylene wax obtained
      before and after three-week cultivation of a fungus Aspergillus sp. AK-3. In
      addition, we present a numerical result which we obtained by applying the
      degradation rate based on the three week cultivation to simulate the transition
      of the weight distribution after cultivation of the fungus for five weeks.

PMID- 15494175
TI  - Mathematical modelling of therapies targeted at bacterial quorum sensing.
AB  - Bacteria commonly use diffusible signal molecules to synchronise their behaviour
      by facilitating population dependent co-ordination. This cell-to-cell signalling
      mechanism is known as quorum sensing (QS) and provides a way of ensuring that
      certain genes are 'switched on' only when a certain signal concentration
      (typically corresponding to a large population density) has been reached. In this
      paper we focus on the QS system of the human pathogen Pseudomonas aeruginosa,
      which employs a complex hierarchy of QS signalling systems, which regulate the
      formation of multiple exoproducts, swarming and biofilm differentiation. In P.
      aeruginosa, the signal molecules are N-acylated homoserine lactones (AHLs; e.g.,
      N-(3-oxododecanoyl)-homoserine lactone [3-oxo-C12-HSL]), which bind to
      transcriptional regulator proteins (LasR in the case of 3-oxo-C12-HSL) to
      activate the expression of target genes including lasI, which codes for the 3-oxo
      C12-HSL synthase. Since the virulence of P. aeruginosa is controlled by QS,
      agents (QSBs) designed to block this cell-to-cell communication have potential as
      novel antibacterials. By drawing on existing models for the reaction kinetics of
      this system, we model a growing population subject to treatment with two kinds of
      QSB, together with a conventional antibiotic. The first kind of QSB is assumed to
      act by diffusing through the cell membrane and then destabilising/sequestering
      LasR, while the second kind remains outside the cell and degrades the AHL signal
      molecule itself. Numerical and mathematical analysis of the resulting systems of
      ordinary differential equations reveals in particular that, while a sufficiently
      high dose of QSB is, in all cases considered, able to reduce the AHL
      concentration (and hence virulence) to a negligible level, the qualitative
      response to treatment is sensitive to parameter values.

PMID- 15494176
TI  - Pain relief: a universal human right.

PMID- 15494177
TI  - Somatosensory volleys and cortical evoked potentials: 'first come, first served'?

PMID- 15494178
TI  - Can we model CRPS type 1?

PMID- 15494179
TI  - Understanding pain management by examining the social context in which pain is
      reported.

PMID- 15494180
TI  - What should we be measuring in behavioral studies of chronic pain in animals?

PMID- 15494181
TI  - Refractoriness cannot explain why C-fiber laser-evoked brain potentials are
      recorded only if concomitant Adelta-fiber activation is avoided.
AB  - Co-activation of Adelta- and C-fiber nociceptors by brief cutaneous laser heat
      stimuli may induce a dual sensation composed of first and second pain but evokes
      only a single, Adelta-fiber related, late laser-evoked potential (LEP). Yet, when
      concomitant activation of Adelta-nociceptors is avoided, C-nociceptor activation
      evokes an ultra-late LEP. As cumulating evidence indicates that late and ultra
      late LEPs may share common generators, investigators have hypothesized that when
      Adelta-fibers trigger a late LEP, the later arriving C-fiber afferent volley
      cannot trigger an ultra-late LEP because underlying generators are in a
      'refractory state'. Better understanding of these interactions could have
      important consequences regarding the functional significance of LEPs. Therefore,
      this hypothesis was tested by applying two consecutive laser stimuli to the hand
      dorsum such as to produce a second Adelta-nociceptor afferent volley arriving at
      generators during their expected 'refractory period'. Results showed that late
      LEPs evoked by the second stimulus were not altered and consequently that this
      hypothesis does not hold. In addition, when stimuli ended the sensory detection
      task, an ample P600 component was recorded. Studies have shown that this
      component is probably related to the P3b component described in other sensory
      modalities. This result provides support to the 'context closure' model
      hypothesizing that this component reflects the closure of information processing
      occurring when expectations are terminated. Altogether, these results suggest
      that late and ultra-late LEPs reflect very general processes, which are mainly
      related to detection and orientation and constitute only a fraction of the
      central processing of both nociceptive inputs.

PMID- 15494182
TI  - Perception and modulation of pain in waking and hypnosis: functional significance
      of phase-ordered gamma oscillations.
AB  - Somatosensory event-related phase-ordered gamma oscillations (40-Hz) to electric
      painful standard stimuli under an odd-ball paradigm were analyzed in 13 high, 13
      medium, and 12 low hypnotizable subjects during waking, hypnosis, and post
      hypnosis conditions. During these conditions, subjects received a suggestion of
      Focused Analgesia to produce an obstructive hallucination of stimulus perception;
      a No-Analgesia treatment served as a control. After hypnosis, a post-hypnotic
      suggestion was given to draw waking subjects into a deep hypnosis with opened
      eyes. High hypnotizables, compared to medium and low ones, experienced
      significant pain and distress reductions for Focused Analgesia during hypnosis
      and, to a greater extent, during post-hypnosis condition. Correlational analysis
      of EEG sweeps of each individual revealed brief intervals of phase ordering of
      gamma patterns, preceding and following stimulus onset, lasting approximately six
      periods. High and medium hypnotizable subjects showed significant reductions in
      phase-ordered gamma patterns for Focused Analgesia during hypnosis and post
      hypnosis conditions; this effect was found, however, more pronounced in high
      hypnotizable subjects. Phase-ordered gamma scores over central scalp site
      predicted subject pain ratings across Waking-Pain and Waking-Analgesia
      conditions, while phase-ordered gamma scores over frontal scalp site predicted
      pain ratings during post-hypnosis analgesia condition. During waking conditions,
      this relationship was present in high, low and medium hypnotizable subjects and
      was independent of stimulus intensity measures. This relationship was unchanged
      by hypnosis induction in the low hypnotizable subjects, but not present in the
      high and medium ones during hypnosis, suggesting that hypnosis interferes with
      phase-ordered gamma and pain relationship.

PMID- 15494183
TI  - NK1 receptor activation leads to enhancement of inhibitory neurotransmission in
      spinal substantia gelatinosa neurons of mouse.
AB  - Substance P (SP) is a well-established pain messenger in the spinal cord,
      although its role in substantia gelatinosa (lamina II) still remains elusive. We
      carried out patch-clamp recordings on lamina II neurons from transverse mouse
      spinal cord slices (P8-12), using the selective NK1 receptor agonist
      [Sar9,Met(O2)11]-SP (SM-SP, 3-5 microM) in the presence of NBQX. Activation of
      NK1 receptors was confirmed after pre-incubation with selective NK1 antagonist
      L732,138 (4 microM) that consistently blocked the effects of SM-SP (nine
      neurons). After SM-SP challenge and spontaneous inhibitory post-synaptic current
      (sIPSC) analysis, 50% of recorded neurons (15 out of 30) were found to display a
      transient increase in frequency; in five neurons this was also associated with
      increase of peak amplitude. Five out of eight neurons displayed pure GABAA
      microM) receptor-mediated sIPSCs, whereas the remaining ones showed mixed
      GABAergic/glycinergic events. After miniature IPSC analysis, a significant
      increase in frequency was observed in three out of 14 SM-SP responsive neurons.
      At least four different morphological types were apparent among NK1-responsive
      neurons after filling with Lucifer Yellow/biocytin: fusiform with dorso-ventral
      dendritic arbors (i); round-to-oval with dendritic arborization mainly directed
      to lamina I (ii) or III (iii), and round-to-oval with dendrites sparsely
      distributed all around the cell body (iv). Thus, there was no correlation between
      morphology and electrophysiological properties of responsive neurons. Our
      observations provide new insights on the processing of sensory neurotransmission
      in spinal cord, and indicate that activation of NK1 receptors is involved in the
      maintenance of the inhibitory tone of substantia gelatinosa interneurons.

PMID- 15494184
TI  - Cognitive modulation of pain-related brain responses depends on behavioral
      strategy.
AB  - Interactions of pain and cognition have been studied in humans and animals
      previously, but the relationship between such behavioral interactions and brain
      activity is unknown. We aimed to show using functional MRI (fMRI) how a
      cognitively demanding task (Stroop) modulates pain-related brain activations and
      conversely, how pain modulates attention-related activity. Reaction time data
      indicated two types of pain responders: subjects in the A group had a faster
      Stroop reaction time when pain was concomitant to the attention task, while those
      in the P group had a slower Stroop performance during painful stimulation. fMRI
      data obtained during Stroop performance with and without noxious stimulation were
      subjected to region of interest analyses. We first tested whether brain activity
      during painful median nerve stimulation was modulated by cognitive load. We next
      tested whether brain activity during the high conflict cognitive task was
      modulated by pain. Pain-related activity in three regions, primary (S1), and
      secondary (S2) somatosensory cortices, and anterior insula, was attenuated by
      cognitive engagement, but this effect was specific to the A group. Pain-related
      activations in the caudal and rostral anterior cingulate cortex (ACC) and
      ventroposterior thalamus were not modulated by cognitive load. None of the areas
      showing attention-related responses, including bilateral dorsolateral prefrontal
      and posterior parietal cortices, were modulated by pain. These findings suggest
      that cortical regions associated with pain can be modulated by cognitive
      strategies. Furthermore, the distinction of behavioral subgroups may relate to
      cognitive coping strategies taken by patients with chronic pain.

PMID- 15494185
TI  - Muscle tenderness in different headache types and its relation to anxiety and
      depression.
AB  - To assess in patients with migraine and tension type headache, both episodic and
      chronic, the extent to which muscle tenderness may relate to anxiety and
      depression, 459 patients with Episodic Migraine (EM, 125), Chronic Migraine (CM,
      97), Episodic Tension Type Headache (ETTH, 82), Chronic Tension Type Headache
      (CTTH, 83), and EM+ETTH (72) were enrolled. For each patient, a psychological
      assessment on the Axis 1 of the DSM-IV and muscle palpation of pericranial and
      cervical muscles were carried out. A Pericranial Muscle Tenderness Score (PTS)
      and a Cervical Muscle Tenderness Score (CTS) were calculated (range 0-3).
      Logistic and linear regression analyses were employed to assess relations between
      muscle tenderness, the demographic variables and psychiatric disorders in the
      different patient groups. Odds ratio for 'male gender' was higher in groups with
      tension type headache. Only EM patients showed a positive association with
      increasing age. Anxiety and depression were significantly associated to CM. A
      significant negative correlation of PTS and CTS was observed in EM patients. In
      relation to male gender, the PTS was significantly lower in EM, ETTH and CTTH;
      CTS was significantly lower in EM, CM, and CTTH. Anxiety and, even more, anxiety
      and depression combined were positively associated to higher PTS and CTS in EM
      patients. Anxiety and depression were also positively associated to higher CTS in
      patients with EM+ETTH. In CTTH patients, PTS only was positively associated to
      anxiety and depression. We conclude that in patients with EM, the presence of
      anxiety or anxiety and depression combined considerably increases the level of
      muscle tenderness in the head and, even more, in the neck, and might facilitate
      the evolution into CM.

PMID- 15494186
TI  - Validation of a screener and opioid assessment measure for patients with chronic
      pain.
AB  - There has been a need for a brief assessment tool for providers who treat chronic
      pain patients to determine potential risk of abuse when prescribed opioids for
      pain. The purpose of this study was to develop and begin the validation of a self
      administered screening tool (Screener and Opioid Assessment for Patients with
      Pain, SOAPP) for chronic pain patients considered for long-term opioid therapy. A
      consensus of 26 pain and addiction experts was obtained on important
      characteristics of chronic pain patients that predict future medication misuse
      using concept mapping. A 24-item SOAPP (version 1.0) was developed based on this
      consensus and was administered to 175 patients who were taking opioids for
      chronic pain. After 6 months, 95 of these patients were re-evaluated. Validation
      of the SOAPP was conducted by identifying those patients exhibiting aberrant drug
      related behavior as determined by any of the following: a positive score on the
      Prescription Drug Use Questionnaire (PDUQ) interview, positive urine toxicology
      screen, and/or ratings by staff as to whether patients had a serious drug
      problem. Of the original 24 items, 14 SOAPP items appeared to predict subsequent
      aberrant behaviors. Coefficient alpha for these 14 items was acceptable for a
      short scale (0.74). Receiver operating characteristics curve analysis yielded an
      area under the curve of 0.881 (P<0.001), suggesting adequate sensitivity and
      specificity for a screening device. These reliability and predictive validity
      results suggest that the SOAPP is a promising step toward screening risk
      potential for substance misuse among persons with chronic pain.

PMID- 15494187
TI  - Beta adrenergic inhibition of capsaicin-induced, NK1 receptor-mediated nerve
      growth factor biosynthesis in rat skin.
AB  - Excitation of primary afferent neurons stimulates the expression of cytokines and
      nerve growth factor (NGF) in innervated tissues. Since NGF is a neurotrophic and
      immunomodulatory factor contributing to inflammatory hyperalgesia and tissue
      response to injury, this study was conducted in order to investigate the
      mechanisms by which afferent neuron stimulation by topical application of
      capsaicin increases NGF in the rat skin. Thereby it was sought to identify
      possible targets for pharmacological modulation of NGF biosynthesis. Topical
      capsaicin (>1 mg/ml ethanol) caused a concentration- and time-dependent increase
      in the concentration of NGF in rat skin. The capsaicin-induced increase of NGF
      was not significantly affected by indomethacin administered at a dose (2 mg/kg)
      that abolishes prostaglandin E2 biosynthesis. The NGF increase was suppressed by
      treatment of rats with the selective tachykinin NK1 receptor antagonist SR140333
      (0.1 mg/kg), and by the beta adrenergic agonist terbutaline (0.3 mg/kg). The
      effect of terbutaline was reversed by the beta adrenergic antagonist propranolol
      (1 mg/kg). Terbutaline also inhibited the increase in NGF caused by intraplantar
      injection of the NK1 receptor agonist substance P (SP), but did not significantly
      affect that caused by carrageenan. The results show that topical administration
      of capsaicin causes a primarily NK1 receptor-dependent increase in the NGF
      content of rat skin, which is susceptible to inhibition by beta adrenergic
      agonists. These observations not only suggest regulation of skin NGF biosynthesis
      by afferent neuronal and adrenergic mechanisms, but also indicate possible
      targets for pharmacological modulation of skin NGF biosynthesis.

PMID- 15494188
TI  - Pain related behaviour in two models of osteoarthritis in the rat knee.
AB  - Osteoarthritis (OA) is a major healthcare burden, with increasing incidence. Pain
      is the predominant clinical feature, yet therapy is ineffective for many
      patients. While there are considerable insights into the mechanisms underlying
      tissue remodelling, there is poor understanding of the link between disease
      pathology and pain. This is in part owing to the lack of animal models that
      combine both osteoarthritic tissue remodelling and pain. Here, we provide an
      analysis of pain related behaviours in two models of OA in the rat: partial
      medial meniscectomy and iodoacetate injection. Histological studies demonstrated
      that in both models, progressive osteoarthritic joint pathology developed over
      the course of the next 28 days. In the ipsilateral hind limb in both models,
      changes in the percentage bodyweight borne were small, whereas marked mechanical
      hyperalgesia and tactile allodynia were seen. The responses in the iodoacetate
      treated animals were generally more robust, and these animals were tested for
      pharmacological reversal of pain related behaviour. Morphine was able to
      attenuate hyperalgesia 3, 14 and 28 days after OA induction, and reversed
      allodynia at days 14 and 28, providing evidence that this behaviour was pain
      related. Diclofenac and paracetamol were effective 3 days after arthritic
      induction only, coinciding with a measurable swelling of the knee. Gabapentin
      varied in its ability to reverse both hyperalgesia and allodynia. The iodoacetate
      model provides a basis for studies on the mechanisms of pain in OA, and for
      development of novel therapeutic analgesics.

PMID- 15494189
TI  - Chronic post-ischemia pain (CPIP): a novel animal model of complex regional pain
      syndrome-type I (CRPS-I; reflex sympathetic dystrophy) produced by prolonged
      hindpaw ischemia and reperfusion in the rat.
AB  - A neuropathic-like pain syndrome was produced in rats following prolonged hindpaw
      ischemia and reperfusion, creating an animal model of complex regional pain
      syndrome-Type I (CRPS-I; reflex sympathetic dystrophy) that we call chronic post
      ischemia pain (CPIP). The method involves placing a tourniquet (a tight fitting O
      ring) on one hindlimb of an anesthetized rat just proximal to the ankle joint for
      3 h, and removing it to allow reperfusion prior to termination of the anesthesia.
      Rats exhibit hyperemia and edema/plasma extravasation of the ischemic hindpaw for
      a period of 2-4 h after reperfusion. Hyperalgesia to noxious mechanical
      stimulation (pin prick) and cold (acetone exposure), as well as mechanical
      allodynia to innocuous mechanical stimulation (von Frey hairs), are evident in
      the affected hindpaw as early as 8 h after reperfusion, and extend for at least 4
      weeks in approximately 70% of the rats. The rats also exhibit spontaneous pain
      behaviors (hindpaw shaking, licking and favoring), and spread of
      hyperalgesia/allodynia to the uninjured contralateral hindpaw. Light-microscopic
      examination of the tibial nerve taken from the region just proximal to the
      tourniquet reveals no signs of nerve damage. Consistent with the hypothesis that
      the generation of free radicals may be partly responsible for CRPS-I and CPIP,
      two free radical scavengers, N-acetyl-L-cysteine (NAC) and 4-hydroxy-2,2,6,6
      tetramethylpiperydine-1-oxyl (Tempol), were able to reduce signs of mechanical
      allodynia in this model.

PMID- 15494190
TI  - Intrathecal tri-cyclic antidepressants produce spinal anesthesia.
AB  - Tri-cyclic antidepressants (TCAs) have been widely used in treating major
      depressive disorders. Recent studies further demonstrated that TCAs have potent
      sodium channel blocking effect, and amitriptyline, one of the TCAs, has a potent
      spinal anesthetic effect. The aim of the study was to evaluate the spinal
      anesthetic effect of various TCAs and to see whether these TCAs could likewise
      act as local anesthetics after a single intrathecal injection. Bupivacaine, a
      potent and long-acting traditional local anesthetic, acted as control. The spinal
      anesthetic effect of nine TCAs (amitriptyline, doxepin, imipramine, trimipramine,
      clomipramine, protriptyline, desipramine, nortriptyline, and amoxapine) and three
      traditional local anesthetics (bupivacaine, lidocaine, and mepivacaine) was
      evaluated in rats and so were dose-response studies of amitriptyline,
      bupivacaine, and lidocaine. Under a given concentration of 5mM, bupivacaine had
      the most potent spinal blockade of motor, propioception, and nociception
      (P<0.001) and the longest duration of action of nociception (P<0.01) among the
      three traditional local anesthetics. Under this concentration, amitriptyline had
      a similar potency but longer duration of spinal blockade of motor, propioception,
      and nociception (P<0.001) than did bupivacaine, whereas several other TCAs had
      similar or less potencies of spinal blockade than did bupivacaine. In dose
      response studies, amitriptyline had a more potent (P<0.005) and longer duration
      (P<0.001) of spinal blockade than did bupivacaine. We concluded that intrathecal
      amitriptyline had a more potent and longer duration of spinal anesthetic effect
      than did bupivacaine, whereas several other TCAs had similar or less potencies
      than did bupivacaine.

PMID- 15494191
TI  - Involvement of cholecystokinin in the opioid tolerance induced by dipyrone
      (metamizol) microinjections into the periaqueductal gray matter of rats.
AB  - The analgesic effect of non-steroidal anti-inflammatory drugs (NSAIDs) is partly
      due to an action upon the periaqueductal gray matter (PAG), which triggers the
      descending pain control system and thus inhibits nociceptive transmission. This
      action of NSAIDs engages endogenous opioids at the PAG, the nucleus raphe magnus
      and the spinal cord. Repeated administration of NSAIDs such as dipyrone
      (metamizol) and acetylsalicylate thus induces tolerance to these compounds and
      cross-tolerance to morphine. Since cholecystokinin plays a key role in opioid
      tolerance, the present study in rats investigated whether PAG cholecystokinin is
      also responsible for tolerance to PAG-microinjected dipyrone. Microinjection of
      cholecystokinin (1 ng/0.5 microl) into PAG blocked the antinociceptive effect of
      a subsequent microinjection of dipyrone (150 microg/0.5 microl) into the same
      site, as evaluated by the tail flick and hot plate tests. Microinjection of
      proglumide (0.4 microg/0.5 microl), a non-selective cholecystokinin antagonist,
      into PAG prevented the development of tolerance to subsequent microinjections of
      dipyrone, as well as cross-tolerance to microinjection of morphine (5 microg/0.5
      microl) into the same site. In rats tolerant to PAG dipyrone, a PAG
      microinjection of proglumide restored the antinociceptive effect of a subsequent
      microinjection of dipyrone or morphine. These results suggest that PAG
      microinjected dipyrone triggers and/or potentiates local opioidergic circuits
      leading to descending inhibition of nociception, on the one hand, and to a local
      antiopioid action by cholecystokinin, on the other. Reiteration of these events
      would then result in an enhancement of cholecystokinin's antiopioid action and
      thus tolerance to opioids and dipyrone in the PAG.

PMID- 15494192
TI  - In vivo evidence for apoptosis, but not inflammation in the hindlimb muscle of
      neuropathic rats.
AB  - Loose ligation of the rat sciatic nerve (chronic constriction injury (CCI) model)
      provokes signs and symptoms like those observed in complex regional pain syndrome
      (CRPS) patients. Neurogenic inflammation is a purported cause of neuropathic pain
      despite inconsistent evidence to support this hypothesis. To clarify this issue,
      we examined effects of CCI on microcirculation, inflammatory cell-cell
      interaction and cell integrity in muscle tissue using intravital fluorescence
      microscopic, molecular and immunohistochemical techniques. CCI-rats, but not sham
      operated animals developed symptoms of neuropathic pain and oedema on the
      ipsilateral hindpaw. Despite signs of neuropathic pain, high resolution in vivo
      multifluorescence microscopy revealed physiological values for functional
      capillary density, leukocyte-endothelial cell interaction and microvascular
      permeability in muscle tissue of CCI-animals, similarly as found in controls,
      indicating absence of perfusion failure and inflammatory cell reaction. However,
      CCI-animals represented with marked apoptosis of bisbenzimide-stained muscle
      tissue cells, as given by in vivo fluorescence microscopic assessment of cell
      death-associated condensation, fragmentation and/or crescent-shaped formation of
      their nuclear chromatin. Apoptosis was further confirmed by increased caspase 3
      protein levels and positive terminal deoxyuridine nick end labeling
      histochemistry. The present study demonstrates that sciatic nerve ligation
      induced neuropathy causes cell apoptosis without concomitant inflammation
      associated microcirculatory dysfunction in muscle tissue. Beside the well-known
      pattern of neuropathic pain, the CCI-model has now additionally been shown to
      reflect the response of muscle tissue to impaired innervation, i.e. prompting
      muscle cells to undergo non-inflammatory apoptotic cell death. This finding
      deserves further investigation in that apoptosis may contribute to neuropathic
      pain conditions like CRPS.

PMID- 15494193
TI  - The protein tyrosine kinase inhibitor, genistein, decreases excitability of
      nociceptive neurons.
AB  - One mechanism by which neurons regulate their excitability is through ion channel
      phosphorylation. Compounds that increase nociceptive neuron excitability can
      cause hyperalgesia or allodynia whereas compounds that decrease nociceptive
      neuron excitability can be used as analgesics to relieve pain arising from
      inflammation or trauma. To identify targets that may cause a decrease in
      nociceptive neuron excitability, we have investigated the effects of genistein, a
      specific inhibitor of protein tyrosine kinases (PTKs), on capsaicin-sensitive
      neurons from cultured rat trigeminal ganglion neurons. It was found that
      genistein decreased the number of evoked action potentials, and hence their
      excitability. To determine whether genistein's effects occur through the
      inhibition of PTKs, we also tested the effects of two of its inactive analogues,
      daidzein and genistin. Whereas daidzein decreased excitability, albeit to a lower
      extent than genistein, excitability was unaffected by genistin. To determine
      which currents are involved in genistein's reduction in nociceptive neuron
      excitability, whole-cell voltage-clamp measurements were performed on voltage
      gated sodium and potassium currents. One hundred micromolar genistein, daidzein
      and genistin inhibited tetrodotoxin-resistant voltage-gated sodium currents 74,
      42, and 3%, respectively. Genistein markedly inhibited delayed rectifier (IK) and
      IA potassium currents, whereas daidzein and genistin were comparatively
      ineffective. In summary, we found that genistein's ability to inhibit nociceptive
      neuron excitability arises primarily from its non-specific inhibition of voltage
      dependent sodium channels.

PMID- 15494194
TI  - The effects of experimenter characteristics on pain reports in women and men.
AB  - The present study investigated the effects of two attributes of the experimenter
      (gender and professional status) on the report and tolerance of pain in male and
      female subjects. 160 non-psychology students (80 male and 80 female, aged 17-59
      years) participated in a cold-pressor task. Subjects were assigned to one of 8
      groups: male (M) and female (F) experimenters tested male (m) and female (f)
      students. In each combination (Mm, Mf, Fm, Ff), the cold-pressor task was
      conducted by either one of two faculty members (high professional) or one of two
      students (low professional). Subjects were asked to immerse their non-dominant
      hand as long as possible in cold water (-1 degrees C). Dependent variables were
      pain threshold, pain tolerance, and pain intensity. Results indicated a
      significant main effect for professional status of the experimenter on pain
      tolerance. Subjects tolerated pain longer when they were tested by a professional
      experimenter. Further, a significant interaction of experimenter gender and
      subject gender on pain tolerance indicated that subjects also tolerated pain
      longer when they were tested by an experimenter of the opposite sex.
      Additionally, a significant main effect for experimenter gender showed higher
      pain intensities for subjects tested by female experimenters. The observation
      that pain responsivity is influenced by the professional status of the
      experimenter might have implications for the study of pain in general and should
      be addressed in more detail in future experiments.

PMID- 15494195
TI  - Intracerebroventricular injection of phospholipases A2 inhibitors modulates
      allodynia after facial carrageenan injection in mice.
AB  - The present study was carried out, using inhibitors to secretory phospholipase A2
      (sPLA2, 12-epi-scalaradial), cytosolic phospholipase A2 (cPLA2, AACOCF3), or
      calcium-independent phospholipase A2 (iPLA2, bromoenol lactone), to compare
      possible contributions of central nervous PLA2 isoforms to the development of
      allodynia after facial carrageenan injection in mice. C57BL/6J (B6) mice showed
      increased responses to facial stimulation using a von Frey hair (1 g force), at 8
      h, 1 day, and 3 days after facial carrageenan injection. On the other hand,
      BALB/c mice did not show increased responses at any of the time points. In both
      B6 and BALB/c mice, intracerebroventricular injection of inhibitors to each of
      the three PLA2 isoforms significantly reduced responses to von Frey hair
      stimulation at 8 h and 1 day after facial carrageenan injection, but at 3 days
      after injection, only the sPLA2 inhibitor had an effect. Since BALB/c mice did
      not show increased responses after facial carrageenan injection, the reduction in
      responses actually indicates that there is loss of normal sensitivity to von Frey
      hair stimulation after intracerebroventricular injection of each of these
      inhibitors, in this strain of mice. The effects of PLA2 inhibitors are unlikely
      to be due simply to inhibition of arachidonic acid generation, since
      intracerebroventricular injection of arachidonic acid also had an anti
      nociceptive effect. The above results support an important role of central
      nervous PLA2s in neurotransmission and pain transmission.

PMID- 15494196
TI  - Laminar distribution of GABAA- and glycine-receptor mediated tonic inhibition in
      the dorsal horn of the rat lumbar spinal cord: effects of picrotoxin and
      strychnine on expression of Fos-like immunoreactivity.
AB  - Inhibitory mechanisms are essential in suppressing the development of allodynia
      and hyperalgesia in the normal animal and there is evidence that loss of
      inhibition can lead to the development of neuropathic pain. We used Fos
      expression to map the distribution of tonically inhibited cells in the healthy
      rat lumbar spinal cord. In a control group, Fos-like immunoreactive (Fos-LI)
      cells were rare, averaging 7.5+/-2.2 cells (mean+/-SEM; N=13 sections) per 20
      microm thick section of dorsal horn. This rose to 103+/-11 (mean+/-SEM; N=20) in
      picrotoxin-treated rats and to 88+/-11 (mean+/-SEM; N=18) in strychnine-treated
      rats. These changes were significant (ANOVA; P<0.001). There were marked regional
      variations in the distribution of Fos-LI cells between picrotoxin- and strychnine
      treated animals. Picrotoxin induced a significant increase in the number of Fos
      LI cells throughout the dorsal horn (lamina I-VI) while strychnine significantly
      elevated Fos-like immunoreactivity only in deep laminae (III-VI). For both
      picrotoxin and strychnine, the increase in Fos-like immunoreactivity peaked in
      lamina V (at 3579+/-319 and 3649+/-375% of control, respectively; mean+/-SEM) but
      for picrotoxin an additional peak was observed in the outer part of lamina II
      (1959+/-196%). Intrathecal administration of both GABAA and glycine receptor
      antagonists has been shown elsewhere to induce tactile allodynia. The present
      data suggest that this allodynia could arise due to blockade of tonic GABAA and
      glycine-receptor mediated inhibition in the deep dorsal horn. GABAA antagonists
      also induce hypersensitivity to noxious inputs. The blockade of tonic inhibition
      in the superficial dorsal horn shown here may underlie this hyperalgesia.

PMID- 15494197
TI  - Chronic orofacial pain among Korean elders: prevalence, and impact using the
      graded chronic pain scale.
AB  - The aims of this study were to investigate the prevalence of orofacial pain
      symptoms in the Korean elderly population, and to evaluate factors associated
      with orofacial pain and graded chronic pain. Of 4,342 Korean elders from the
      cohort of Korean National Interview Survey of Oral Health Status in 2000,
      telephone interviews were conducted on a stratified random sample of 1,032 people
      aged 55 years or older. Prevalence of five orofacial pain symptoms (jaw joint
      pain, face pain, toothache, oral sores, and burning mouth) in the past 6 months
      along with questions from the graded chronic pain scale were assessed by
      telephone using a structured questionnaire. The results suggested that the 6
      month prevalence of joint pain (15.5%), face pain (9.3%), toothache (26.8%), oral
      sores (26.2%), and burning mouth (14.2%) in Korean elders were higher than in
      studies on Caucasian populations. Painful oral sores and burning mouth had higher
      prevalence for females than for males. Subjects with joint pain, burning mouth or
      toothache pain were more likely to report high levels of a pain-related
      disability compared with subjects not reporting those symptoms. There were no age
      group differences in pain intensity, but the older age group reported a higher
      number of disability days because of their pain. Chronic orofacial pain is a
      substantial health problem in the elderly population.

PMID- 15494198
TI  - Involvement of the histaminergic system in the nociceptin-induced pain-related
      behaviors in the mouse spinal cord.
AB  - Intrathecal (i.t.) injection of nociceptin elicited a behavioral response mainly
      consisting of biting and licking, which were eliminated by the i.t. co
      administration of opioid receptor-like-1 (ORL-1) receptor antagonists. The
      behavioral response induced by nociceptin was characteristically similar to that
      by i.t.-administered histamine, and was attenuated by i.t. co-administration of
      the H1 receptor antagonists, but not by the H2 receptor antagonists, whereas the
      H3 receptor antagonist promoted the nociceptin-induced behavior. H1 receptor
      knockout (H1R-KO) mice did not show the nociceptin-induced nociceptive behavior,
      which was observed in wild-type mice. Pretreatment with a histamine antiserum or
      a histidine decarboxylase inhibitor resulted in a significant reduction of the
      response to nociceptin. The previous studies showed that NK1 receptor antagonists
      and a novel substance P (SP)-specific antagonist given i.t. could reduce the
      behavioral response to nociceptin and histamine. On the other hand, the
      nociceptive response induced by nociceptin, but not histamine, was completely
      attenuated by the i.t. co-administration of agonists for GABAA and GABAB
      receptors. In contrast, the antagonists for GABAA and GABAB receptors injected
      i.t. showed same nociceptive response with nociceptin and histamine, and their
      nociceptive responses were significantly blocked by the i.t. co-administration of
      the H1 receptor antagonists, but not H2 receptor antagonists or ORL-1 receptor
      antagonists. The present results suggest that the activation of the ORL-1
      receptor by nociceptin may induce the disinhibition of histaminergic neuron and
      enhance the release of histamine, which subsequently acts on the H1 receptor
      located on the SP-containing neurons to produce the spinal cord-mediated
      nociceptive response.

PMID- 15494199
TI  - Gender differences in patient-spouse interactions: a sequential analysis of
      behavioral interactions in patients having osteoarthritic knee pain.
AB  - Theory and research suggest that spousal responses to displays of pain behavior
      can vary markedly. To our knowledge, observational research on spousal responses
      to pain behavior has been carried out only in chronic low back pain patients, but
      not in other populations. In this study systematic observations were conducted of
      interactions occurring between 50 married osteoarthritis patients (25 male and 25
      female) and their respective spouses. Observations were conducted as the patient
      and spouse performed three common household tasks: sweeping the floor, folding
      laundry, and carrying small, artificial logs from one side of the room to the
      other. Contrary to prior research on chronic low back pain this study found that
      in osteoarthritis patients spouse facilitative behavior preceded and followed
      patient pain behavior significantly more often than did spouse solicitous
      behavior. A gender difference in spousal responding to pain behavior also was
      observed in that wives were significantly more likely to show facilitative
      behavior preceding and following patient pain behavior than were husbands. The
      implications of these findings for future research and clinical interventions
      focused on patient-spouse interactions are discussed.

PMID- 15494200
TI  - An evaluation of sex differences in psychological and physiological responses to
      experimentally-induced pain: a path analytic description.
AB  - A cold pressor task (CPT) was used with 203 college students (112 women and 91
      men) in a study of sex differences in pain response. Physiological measures were
      taken before and after pain induction, and sex-differentiating personality traits
      were assessed with the Personal Attributes Questionnaire (PAQ). The Pain
      Catastrophizing Scale (PCS) was given with standard instructions prior to the
      CPT, and it was re-administered after the CPT with modified instructions to
      assess catastrophic thinking during the CPT. Hypotheses were formulated into an
      explanatory model that was evaluated by path analysis. Pain induction elevated
      blood pressures and cortisol levels for both sexes, but systolic blood pressure
      reactivity and cortisol response were greater in men, even with sex differences
      in CPT tolerance times controlled statistically. Post-CPT PCS scores were
      positively related to pain ratings and negatively related to tolerance, but
      baseline PCS scores did not predict tolerance or pain ratings. Pre-PCS scores
      were not well correlated with post-PCS scores (r=0.46) and underestimated post
      PCS scores, particularly for women. The Sex difference on the post-CPT PCS was
      largely attributable to the PAQ personality trait of Emotional Vulnerability. The
      differential results obtained from assessing catastrophizing before and after the
      CPT emphasized the importance of specifying the context in which catastrophizing
      is assessed (both timing and instructions). Theoretical considerations in the
      construct of catastrophizing are also highlighted, including, but not limited to,
      the confounding of variables such as pain intensity and unpleasantness.

PMID- 15494201
TI  - Sedative music reduces anxiety and pain during chair rest after open-heart
      surgery.
AB  - Open-heart surgery patients report anxiety and pain with chair rest despite
      opioid analgesic use. The effectiveness of non-pharmacological complementary
      methods (sedative music and scheduled rest) in reducing anxiety and pain during
      chair rest was tested using a three-group pretest-posttest experimental design
      with 61 adult postoperative open-heart surgery patients. Patients were randomly
      assigned to receive 30 min of sedative music (N=19), scheduled rest (N=21), or
      treatment as usual (N=21) during chair rest. Anxiety, pain sensation, and pain
      distress were measured with visual analogue scales at chair rest initiation and
      30 min later. Repeated measures MANOVA indicated significant group differences in
      anxiety, pain sensation, and pain distress from pretest to posttest, P<0.001.
      Univariate repeated measures ANOVA (P< or =0.001) and post hoc dependent t-tests
      indicated that in the sedative music and scheduled rest groups, anxiety, pain
      sensation, and pain distress all decreased significantly, P<0.001-0.015; while in
      the treatment as usual group, no significant differences occurred. Further,
      independent t-tests indicated significantly less posttest anxiety, pain
      sensation, and pain distress in the sedative music group than in the scheduled
      rest or treatment as usual groups (P<0.001-0.006). Thus, in this randomized
      control trial, sedative music was more effective than scheduled rest and
      treatment as usual in decreasing anxiety and pain in open-heart surgery patients
      during first time chair rest. Patients should be encouraged to use sedative music
      as an adjuvant to medication during chair rest.

PMID- 15494202
TI  - Spontaneous discharge and increased heat sensitivity of rat C-fiber nociceptors
      are present in vitro after plantar incision.
AB  - Postoperative pain is characterized by spontaneous pain at the surgical site and
      increased pain due to movements. To study postoperative pain mechanisms, we
      investigated discharge properties of mechano-heat sensitive C-fiber afferents
      innervating the rat glabrous hindpaw skin 1 day after plantar incision. Behaviors
      indicating spontaneous pain, heat and mechanical hyperalgesia were present 1 day
      after incision. Recording of afferents using in vitro glabrous skin-nerve
      preparation showed that more C-fibers from the incision had spontaneous discharge
      than control rats. The spontaneously discharging fibers from incised rats had
      lower heat response threshold compared with fibers without spontaneous activity.
      In all fibers less than 2 mm from the incision, an increased percentage responded
      to lower temperatures (35-41 degrees C), the mean heat response threshold was 3.1
      degrees C less, the stimulus-response function for heat evoked response was
      shifted to the left and the total number of impulses in response to a 33-48
      degrees C heat stimulus was increased. Heat responses of C-fibers more than 2 mm
      from the incision, however, were not different from control. The mean mechanical
      response thresholds, measured by a servo force-controlled stimulator, were not
      different between groups. The total spikes evoked at supra-threshold mechanical
      stimulation were not increased in afferents from the incision. In conclusion, 1
      day after incision, when behaviors indicating spontaneous pain, heat and
      mechanical hyperalgesia are present, C-fibers close to incision showed
      spontaneous discharge and sensitization to heat but not to mechanical stimuli, in
      vitro.

PMID- 15494203
TI  - Do medical factors predict disability in older adults with persistent low back
      pain?
AB  - Persistent low back pain (LBP) is one of the most common and challenging
      persistent pain conditions in older adults. Medical comorbidity also is common in
      these individuals, but its impact on disability has not been examined. The
      purpose of this study was, using a cross-sectional design, to examine the
      functional impact of pain-related and general medical comorbidity on 100
      community dwelling older adults (mean age 74.3) with persistent mechanical LBP.
      Subjects received a structured history and physical examination, lumbosacral
      spine X-rays, and standardized tests of physical function. Pain-related variables
      included intensity, duration, extent, and lumbar motion-induced pain. General
      medical variables included age, comorbidity, number of medications, depressive
      symptoms, back range of motion, body mass index, and severity of radiographic
      pathology. Function/disability measures included self-reported disability, gait
      speed, and mean number of static lifts and amount of work performed during a
      dynamic lifting task. Structural equation modeling was used to evaluate the
      influence of pain and medical variables on function/disability. The overall
      regression model indicated pain and medical variables were significantly
      associated with function/disability measures (R2=0.45, P<0.01). Individual
      regression coefficients, however, indicated that only pain duration (r=-0.36,
      P<0.05) and pain severity (r=0.37, P<0.001) were significantly associated with
      function/disability. Despite the prevalence of medical co-morbidities in older
      PLBP subjects, they appear to be of limited utility in understanding level of
      disability. These findings also underscore the need to optimize pain treatment in
      independent older adults to optimize physical function and delay the onset of
      dependent living status.

PMID- 15494204
TI  - Catastrophizing, coping and validation for chronic pain: a comment on Boothby et
      al. (2004).

PMID- 15494205
TI  - In vitro and in vivo modulation of vascular barrier integrity by sphingosine 1
      phosphate: mechanistic insights.
AB  - Sphingosine 1-phosphate (S1P), a biologically active lipid growth factor, induces
      robust endothelial cell activation resulting in cellular locomotion, vascular
      maturation and angiogenesis. Recent work by our laboratory has demonstrated S1P
      to enhance the cellular barrier function of the vascular endothelium. S1P-induced
      modulation of vascular permeability is effected through profound cytoskeletal
      reorganization initiated by cell surface receptor-mediated G protein activation
      and downstream signaling via the Rho family of small GTPases. The details of the
      downstream signaling mechanism remain an active area of in vitro investigation.
      Translational investigation suggests a profound impact of S1P administration in
      the modulation of edema formation in disease state manifest as acute inflammatory
      lung injury in which increased vascular permeability is a hallmark feature. These
      data support an exciting potential therapeutic role for S1P in vascular barrier
      enhancement necessary for the treatment of critically ill patients.

PMID- 15494206
TI  - The cardiac beta2-adrenergic signalling a new role for the cPLA2.
AB  - The cardiac actions of catecholamines have long been attributed to the
      predominant beta(1)-AR subtype that couples to the classical Gs/AC/cAMP pathway.
      Recent research clearly indicates that cardiac beta(2)-ARs play a functional role
      in healthy heart and assume increasing importance in failing and aged heart.
      beta(2)-ARs are primarily coupled to an atypical compartmentalized cAMP pathway,
      regulated by phosphorylation and/or oligomerization of beta(2)-ARs, and under the
      control of additional beta(2)-AR/Gi-coupled lipidic pathways, the impact of which
      seems to vary depending on the animal species, the developmental and
      pathophysiological state. This review focuses, more especially, on one of the
      last identified beta(2)-AR/Gi pathway, namely the cPLA(2).

PMID- 15494207
TI  - Sumoylation of internally initiated Sp3 isoforms regulates transcriptional
      repression via a Trichostatin A-insensitive mechanism.
AB  - Sp3 is a ubiquitously expressed member of the Sp family of transcription factors
      that encodes three proteins, Sp3, M1 and M2, with differing capacities to
      stimulate or repress transcription. As part of ongoing efforts to study the
      functions of Sp3 isoforms, we employed a yeast "two-hybrid" screen to identify
      Sp3-binding proteins. This screen resulted in the identification of Ubc9, a SUMO
      1 conjugating enzyme, as an M2-binding protein, and consistent with these results
      sequence analyses identified consensus sumoylation motifs within several Sp
      family members. Western blots probed with anti-Sp3 detected a high molecular
      weight Sp3 isoform that is stabilized by a SUMO-1 hydrolase inhibitor, and this
      protein is also bound by anti-SUMO-1 antiserum. Transient transfection assays
      with epitope-tagged-SUMO-1 and GFP-SUMO-1 fusion proteins confirmed that Sp3, M1
      and M2 proteins are sumoylated in vivo. Substitution of arginine for lysine at
      one putative site of sumoylation, lysine(551), blocked sumoylation of all Sp3
      isoforms in vivo and led to a marginal increase in Sp3-mediated trans-activation
      in insect and mammalian cells. In contrast, introduction of this amino acid
      substitution within M1 converted it into a potent transcriptional trans
      activator. We conclude that Sp3 isoforms are sumoylated in vivo and this post
      translational modification plays an important role in the regulation of Sp3
      mediated transcription.

PMID- 15494208
TI  - CD38 cleavage in fMLP- and IL-8-induced chemotaxis is dependent on p38 MAP kinase
      but independent of p44/42 MAP kinase.
AB  - In this study, we examined the mechanism by which CD38 cleavage is regulated
      through the mitogen-activated protein (MAP) kinases after stimulation by fMLP and
      interleukin-8 (IL-8) in neutrophils. Both fMLP and IL-8 increased chemotaxis and
      decreased CD38 protein in neutrophils, but did not change CD38 mRNA levels. Both
      fMLP and IL-8 increased CD38 in supernatants, which was inhibitable with PMSF.
      fMLP stimulation resulted in phosphorylation of p38 MAP kinase and p42/44 MAP
      kinase (ERK). SB20358, a p38 MAP kinase inhibitor, down-regulated neutrophil
      chemotaxis. Conversely, PD98059, an ERK inhibitor, did not influence chemotaxis
      to either agonist. The addition of SB20358 blocked the decrease of CD38 on
      neutrophils and the increase in supernatants induced by fMLP or IL-8, whereas
      PD98059 did not. These findings suggest that CD38-mediated chemotaxis to fMLP or
      IL-8 is characterized by proteolytic cleavage of CD38 and signaling through p38
      MAP kinase. Activation of the protease for cleavage appears to be a postreceptor
      event that is dependent on p38 MAP kinase signaling.

PMID- 15494209
TI  - Cypermethrin blocks a mitochondria-dependent apoptotic signal initiated by
      deficient N-linked glycosylation within the endoplasmic reticulum.
AB  - The endoplasmic reticulum (ER) serves as a critical site of protein synthesis and
      processing. The temperature-sensitive hamster fibroblast cell line (tsBN7)
      displays deficient N-linked glycosylation activity at the restrictive temperature
      and activates cellular apoptosis. Temperature-shifted tsBN7 cells display
      induction of Grp78 and Gadd153, genes known to be induced by ER stress, and
      activate apoptosis via the release of cytochrome c from the mitochondria.
      Cyclosporin A (CsA), a potent blocker of the mitochondrial permeability
      transition pore (PTP), was sufficient to block cytochrome c release and to rescue
      tsBN7 cells from apoptosis. CsA-treated cells displayed Grp78 induction at the
      restrictive temperature, consistent with an ER stress signal being carried to the
      nucleus, while the apoptosis-associated transcription factor, Gadd153, displayed
      only a mild induction. Cypermethrin, a type II pyrethroid known to perturb Ca(2+)
      signaling in neuronal cells, was sufficient to arrest apoptosis under these
      conditions. This work identifies type II pyrethroids as a valuable new tool in
      the characterization of cellular stress signaling pathways.

PMID- 15494210
TI  - Disruption of microtubules leads to glucocorticoid receptor degradation in HeLa
      cell line.
AB  - The role of microtubules (MTs) in steroid hormone-dependent human glucocorticoid
      receptor (hGR) activation/translocation is controversial. It was demonstrated
      recently that colchicine (COL) down-regulates hGR-driven genes in primary human
      hepatocytes by a mechanism involving inhibition of hGR translocation to the
      nucleus. To investigate whether inhibition of hGR translocation is the sole
      reason for its inactivation, we used human cervical carcinoma cells (HeLa) as a
      model. Herein we present evidence that perturbation of microtubules in HeLa cells
      leads to rapid time- and dose-dependent degradation of hGR protein. Degradation
      is proteasome mediated as revealed by its reversibility by proteasome inhibitor
      MG132. Moreover, degradation was observed for neither wt-hGR nor hGR mutants
      S226A and K419A in transiently transfected COS-1 cells. On the other hand, c-jun
      N-terminal kinase (JNK) seems not to be involved in the process because JNK
      inhibitor 1,9-Pyrazoloanthrone (SP600125) does not reverse hGR degradation.
      Similarly, another hGR functional antagonist, nuclear factor kappa beta
      (NFkappaB), did not play any role in the degradation process.

PMID- 15494211
TI  - Serum withdrawal kills U937 cells by inducing a positive mutual interaction
      between reactive oxygen species and phosphoinositide 3-kinase.
AB  - Reactive oxygen species (ROS) can be generated following cell stimulation and
      function as intracellular signaling molecules. To determine signaling components
      involved in ROS induction, human U937 blood cells grown in 10% serum were exposed
      to serum-free media. It was previously reported that serum withdrawal (SW) killed
      cells by elevating cellular ROS levels. This study showed that SW activates
      phosphoinositide 3-kinase (PI3K). PI3K activation was evident after the ROS
      levels began increasing, and an antioxidant blockade of this increase resulted in
      PI3K activation suppression. Interestingly, the inhibition of PI3K
      activity/activation using either its specific inhibitor or dominant-negative
      mutant attenuated the subsequent additional increase in the ROS levels. These
      results suggest that SW-induced ROS activate PI3K, which in turn promotes the
      process leading to ROS accumulation. The present study also revealed that both
      ROS and PI3K support SW-induced cell death by activating stress-activated protein
      kinase/c-Jun N-terminal kinase (SAPK/JNK). Overall, it appears that SW triggers a
      positive mutual interaction between ROS and PI3K, which amplifies signals
      required for the induction of an SAPK-dependent death pathway.

PMID- 15494212
TI  - Identification of a protein kinase which phosphorylates a subunit of the 26S
      proteasome and changes in its activity during meiotic cell cycle in goldfish
      oocytes.
AB  - The proteasome is involved in the progression of the meiotic cell cycle in fish
      oocytes. We reported that the alpha4 subunit of the 26S proteasome, which is a
      component of the outer rings of the 20S proteasome, is phosphorylated in immature
      oocytes and dephosphorylated in mature oocytes. To investigate the role of the
      phosphorylation, we purified the protein kinase from immature oocytes using a
      recombinant alpha4 subunit as substrate. A protein band which well corresponded
      to the kinase activity was identified as casein kinase Ialpha (CKIalpha). Two
      dimensional (2D) PAGE analysis showed that part of the alpha4 subunit was
      phosphorylated by CKIalpha in vitro. This spot was detected in purified immature
      26S proteasome but not in mature 26S proteasome, demonstrate that the alpha4
      subunit is phosphorylated by CKIalpha meiotic cell cycle dependently.

PMID- 15494214
TI  - Two G protein-coupled receptors activate Na+/H+ exchanger isoform 1 in Chinese
      hamster lung fibroblasts through an ERK-dependent pathway.
AB  - The sodium hydrogen exchanger isoform 1 (NHE1) is present in nearly all cells.
      Regulation of proton flux via the exchanger is a permissive step in cell growth
      and tumorgenesis and is vital in control of cell volume. The regulation of NHE1
      by growth factors involves the Ras-extracellular signal regulated kinase (ERK)
      pathway, however, the mechanism for G protein-coupled receptor (GPCR) activation
      of NHE1 is not well established. In this report, the relationship between GPCRs,
      ERK, and NHE1 in CCL39 cells is investigated. We give evidence that two agonists,
      the specific alpha(1)-adrenergic agonist, phenylephrine and the water-soluble
      lipid mitogen, lysophosphatidic acid (LPA) activate NHE1 in CCL39 cells.
      Activation of ERK by phenylephrine and LPA occurs in a dose- and time-dependent
      manner. Optimal ERK activation was observed at 10 min and displayed a maximum
      stimulation at 100 microM phenylephrine and 10 microM LPA. alpha(1)-Adrenergic
      stimulation also led to a rise in steady-state pH(i) of 0.16+/-0.02 pH units, and
      incubation with LPA induced a 0.43+/-0.06 pH unit increase in pH(i).
      Phenylephrine-induced activation of NHE1 transport and ERK activity was inhibited
      by pretreating the cells with the MEK inhibitor PD98059. While only half of the
      LPA activatable exchange activity was abolished by PD98059 and U0126. To further
      demonstrate the specificity of the phenylephrine and LPA regulation of NHE1 and
      ERK, CCL39 cells were transfected with a kinase inactive MEK. The data indicate
      that ERK activation is essential for phenylephrine stimulation of NHE1, and that
      ERK and RhoA are involved in LPA stimulation of NHE1 by more than one mechanism.
      In addition, evidence of the convergence of these two pathways is shown by the
      loss of NHE1 activity when both pathways are inhibited and by the partial
      additivity of the two agonists on ERK and NHE1 activity. These studies indicate a
      direct involvement of ERK in the alpha(1)-adrenergic activation of NHE1 and a
      significant role for both ERK and RhoA in LPA stimulation of NHE1 in CCL39
      fibroblasts.

PMID- 15494213
TI  - Herpes virus proteins ICP0 and BICP0 can activate NF-kappaB by catalyzing
      IkappaBalpha ubiquitination.
AB  - The immediate early proteins ICP0 and BICP0 from Herpes virus are promiscuous
      activators of both viral and cellular genes and play a critical role in virus
      life cycle. Here we report that ICP0 and BICP0 could induce NF-kappaB
      translocation from cytoplasm into nucleus and strongly activate NF-kappaB
      responsive genes specifically. This process was dependent on the RING domain of
      both proteins. In addition, ICP0 interacted specifically with IkappaBalpha and
      its activating effect was attenuated by Ubch5A(C85A) and MG132, but not by
      IkappaBalpha(S32A/S36A). Remarkably, IkappaBalpha was poly-ubiquitinated by both
      ICP0 and BICP0, in vitro and in vivo. These data indicate that ICP0 and BICP0,
      functioning as ubiquitin ligases, are bona fide activators of NF-kappaB signaling
      pathway. Our study identifies a new way ICP0 and BICP0 explore to regulate gene
      expression.

PMID- 15494215
TI  - Mitochondria from TRAIL-resistant prostate cancer cells are capable of responding
      to apoptotic stimuli.
AB  - TNFalpha-related apoptosis inducing ligand (TRAIL) has been shown to induce
      apoptosis in prostate cancer cells. However, some prostate cancer cells, such as
      LNCaP are resistant to TRAIL. In addition to the involvement of several pathways
      in the TRAIL-resistance of LNCaP, it has been shown that mitochondrial response
      to TRIAL is low in these cells. Therefore, in this study, using in vitro cell
      free and reconstitution models, we have demonstrated that mitochondria from these
      cells are capable of responding to apoptotic stimuli. Furthermore, experiments to
      determine the influence of cytochrome c on apoptotic response noted that
      incubation of cytosol with exogenous cytochrome c induced truncation of Bid. We
      have demonstrated that truncation of Bid by exogenous cytochrome c is mediated
      through the activation of caspases-9 and -3. Incubation of cytosol with
      recombinant caspases-9 and -3 in the absence or presence of inhibitors showed
      that activation of caspase-9, leading to the activation of caspase-3 was
      necessary for the truncation of Bid. Published results indicate that in apoptotic
      cells cytochrome c is released from the mitochondria in two installments, an
      early small amount and a late larger amount. Our results suggest that the initial
      release of cytochrome generates tBid that is capable of translocation into the
      mitochondria causing further release of cytochrome c. Thus, in addition to
      providing functional explanation for the biphasic release of cytochrome c from
      mitochondria, we demonstrate the presence of a feedback amplification of
      mitochondrial apoptotic signal.

PMID- 15494216
TI  - Protein kinase C delta is not activated by caspase-3 and its inhibition is
      sufficient to induce apoptosis in the colon cancer line, COLO 205.
AB  - Activation of protein kinase C delta (PKCdelta) is believed to be pro-apoptotic.
      PKCdelta is reported to be reduced in colon cancers. Using a colon cancer cell
      line, COLO 205, we have examined the roles of PKCdelta in apoptosis and of
      caspase-3 in the activation and inhibition of PKCdelta. PKCdelta activation with
      bistratene A and its inhibition with rottlerin induced apoptosis. Effects of PKC
      activators and inhibitors were additive, suggesting that PKCdelta down-regulation
      was responsible for the effects on apoptosis. Different apoptotic pathways
      induced PKCdelta cleavage, but the fragment produced was inactive in kinase
      assays. Caspase-3 inhibition did not block DNA fragmentation or PKCdelta
      proteolysis despite blocking intracellular caspase-3 activity. Calpain inhibition
      with calpeptin did not prevent TPA-induced PKCdelta cleavage. We conclude that in
      colonocytes, inhibition of PKCdelta is sufficient to lead to caspase-3
      independent apoptosis. Caspase-3 does not cleave PKCdelta to an active form, nor
      does caspase-3 inhibition block apoptosis.

PMID- 15494217
TI  - c-Src is involved in regulating signal transmission from PDGFbeta receptor
      GPCR(s) complexes in mammalian cells.
AB  - We have reported that the platelet-derived growth factor receptor-beta (PDGFbeta)
      forms a novel signaling complex with G protein-coupled receptors (GPCR) (e.g.
      S1P(1) receptor) that enables more efficient activation of p42/p44 mitogen
      activated protein kinase (MAPK) in response to PDGF and sphingosine 1-phosphate
      (S1P). We now demonstrate that c-Src participates in regulating the endocytosis
      of PDGFbeta receptor-GPCR complexes in response to PDGF. This leads to
      association of cytoplasmic p42/p44 MAPK with the receptor complex in endocytic
      vesicles. c-Src is regulated by G protein betagamma subunits and can interact
      with beta-arrestin. Indeed, the PDGF-dependent activation of p42/p44 MAPK was
      reduced by over-expression of the C-terminal domain of GRK2 (sequesters
      Gbetagamma subunits), the clathrin-binding domain of beta-arrestin and by
      inhibitors of c-Src and clathrin-mediated endocytosis. Moreover, PDGF and S1P
      induce the recruitment of c-Src to the PDGFbeta receptor-S1P(1) receptor complex.
      This leads to a G protein/c-Src-dependent tyrosine phosphorylation of Gab1 and
      accumulation of dynamin II at the plasma membrane, a step required for
      endocytosis of the PDGFbeta receptor-GPCR complex. These findings provide
      important information concerning the molecular organisation of novel receptor
      tyrosine kinase (RTK)-GPCR signal relays in mammalian cells.

PMID- 15494219
TI  - Doppler optical coherence tomography for measuring flow in engineered tissue.
AB  - The engineering of human tissue represents a major paradigm shift in clinical
      medicine. Early embodiments of tissue engineering are currently being taken
      forward to the clinic by production methods that are essentially extensions of
      laboratory manual procedures. However, to achieve the status of routine large
      scale clinical practice, automation and scale-out processes are required. This in
      turn will require the development of reliable on-line monitoring and control
      systems. This paper examines one demand of crucial importance, namely the real
      time in vitro monitoring of the flow characteristics through growing tissue since
      this has a complex interrelationship. Doppler optical coherence tomography (DOCT)
      is a recently developed imaging technique for studying the rheological properties
      of tissues in vivo. Capable of non-invasive imaging in real time with high
      resolution, it is potentially ideal for the continuous monitoring of engineered
      tissues in vitro. As a base line, the current status of DOCT in vivo is therefore
      reviewed. This paper also reports the first preliminary use of DOCT in tissue
      engineering. The application described involves the imaging of a fully developed
      laminar flow through a combined tissue fabrication/bioreactor with a tissue
      engineered construct (substitute blood vessel) in situ.

PMID- 15494220
TI  - Structural information on nanomolecular systems revealed by FRET.
AB  - Our newly developed fluorescence resonance energy transfer (FRET) based
      technique, fluorescence nanotomography (FN), is used to determine the morphology
      and dynamics of some soft materials and bio-molecules by attaching donor (D)
      fluorophores and acceptors (A) to the investigated structure and using
      fluorescence lifetime measurements to reveal the D-A distance distribution
      function rhoDA(r). We report the effect of the limited sizes of the donor and
      acceptor, effect of porous polymer, and molecular structure and phase transition
      in phospholipid bilayers.

PMID- 15494221
TI  - High light field confinement for fluorescent correlation spectroscopy using a
      solid immersion lens.
AB  - In this paper we present recent single molecule detection experiment using a
      solid immersion lens (SIL) for fluorescent correlation spectroscopy measurements.
      We compared the performance of the SIL in combination with an air objective (40x,
      numerical aperture (NA)=1.15) with a water immersion objective (40x, NA=0.6) in a
      confocal microscope system (ConfoCorr 1). Important parameters for single
      molecule experiments such as collection efficiency and excitation field
      confinement were investigated. Although the two set-ups have similar numerical
      aperture the measurements demonstrated higher field confinement and better
      collection efficiency for the SIL system in comparison to the conventional
      confocal set-up. Adding spherical aberrations shifts the sample volume up to 4
      microm away from the plane surface of the SIL and conserves a diffraction limited
      focal volume. In this case the FCS autocorrelation demonstrates a free 3D
      diffusion of dye molecules in a highly confined light field.

PMID- 15494222
TI  - Detection of genetically modified organisms by electrochemiluminescence PCR
      method.
AB  - With the development of biotechnology, more and more genetically modified
      organisms (GMOs) have entered commercial market. Because of the safety concerns,
      detection and characterization of GMOs have attracted much attention recently. In
      this study, electrochemiluminescence polymerase chain reaction (ECL-PCR) combined
      with hybridization technique was applied to detect the GMOs in genetically
      modified (GM) soybeans and papayas for the first time. Whether the soybeans and
      the papayas contain GM components was discriminated by detecting the Cauliflower
      mosaic virus 35S (CaMV35S) promoter. The experiment results show that the
      detection limit for CaMV35S promoter is 100 fmol, and the GM components can be
      clearly identified in GM soybeans and papayas. The technique may provide a new
      means in GMOs detection due to its simplicity and high efficiency.

PMID- 15494223
TI  - Monitoring of lung tumour cell growth in artificial membranes.
AB  - Morbidity of many tumour types is associated with invasion of tumour cells
      through the basement membrane and subsequent metastasis to vital organs. Tumour
      invasion is frequently detected late on as many patients present with advanced
      disease. The method of detecting invasion is through conventional histological
      staining techniques, which are time consuming and require processing of the
      sample. This can affect interpretation of the results. In this study, a new
      imaging technique, optical coherence tomography (OCT), was used to monitor lung
      tumour cell growth in two artificial membranes composed of either collagen type I
      or Matrigel. In parallel, standard histological section analysis was performed to
      validate the accuracy of the monitoring by OCT. Cross-sectional images from OCT
      revealed that lung tumour cells infiltrated only when low cell seeding density (5
      x 10(5)) and low collagen concentration (1.5 mg/ml) were combined. The cells
      could be easily differentiated from the artificial membranes and appeared as
      either a brighter layer on the top of the membrane or brighter foci embedded
      within the darker membrane. These cell-membrane morphologies matched remarkably
      to the standard histological section images. Our results suggest that OCT has a
      great potential to become a useful tool for fast and robust imaging of cell
      growth in vivo and as a potential assessment of cell invasion.

PMID- 15494224
TI  - High sensitive approach for point mutation detection based on
      electrochemiluminescence.
AB  - An electrochemiluminescence-polymerase chain reaction (ECL-PCR) method for point
      mutation detection has been developed. The target is amplified using a tris
      (bipyridine) ruthenium (TBR)-labeled forward and a biotinylated reverse primer.
      The amplification products are digested with specific restriction enzyme, then
      captured onto streptavidin-coated paramagnetic beads, and detected by measuring
      the ECL signal of the TBR label. The established technique was further applied to
      detect a specific point mutation in H-ras oncogene in T24 cell line. The results
      show that the system has a low detection limit of 100 fmol and a linear range of
      more than 3 orders of magnitude for H-ras amplicon; the two genotypes can be
      reliably discriminated. In summary, the mutant specific ECL-PCR method can be
      used to detect a point mutation that creates or destroys a restriction site in
      any gene. It is useful in single nucleotide polymorphism (SNP) and mutation
      detection due to its safety, high sensitivity and simplicity.

PMID- 15494225
TI  - A novel method for measuring photosynthesis using delayed fluorescence of
      chloroplast.
AB  - Photosynthesis is the most important chemical reaction in the world. The
      measurement of plant photosynthesis rate plays an important role in agriculture.
      Light-induced delayed fluorescence (DF) in plants is an intrinsic label of the
      efficiency of charge separation at P680 in photosystem II (PS II). In this paper,
      we have developed a biosensor that can accurately measure the plant
      photosynthesis ability by means of DF. Compared with common methods for measuring
      the photosynthesis rate based on consumption of CO2, the proposed technique can
      quantify the plant photosynthesis ability with less influence of the environment.
      The biosensor is an all-weather measuring instrument, it has its own illumination
      power and utilizes intrinsic DF as the measurement marker. The current
      investigation has revealed that, there is a good correspondence between the
      results measured by the biosensor and that by commercially available portable
      photosynthesis system under controlled conditions. We thus conclude that DF is an
      excellent marker for evaluating plant photosynthesis ability under its biological
      status with less interferences of the environment.

PMID- 15494226
TI  - Improvement of low-level light imaging performance using optical clearing method.
AB  - Low-level light-emitting imaging technique often detects the light emerged at the
      tissue surface that is generated internally from a specific target. However, in
      most cases, the high scattering nature of biological tissue limits the
      sensitivity and spatial resolution of this imaging modality. In this paper, we
      report that a significant improvement of chemiluminescence (CL) imaging
      performance in terms of both sensitivity and spatial resolution can be achieved
      by use of the topical application of glycerol solution onto tissue sample, i.e.
      optical clearing approach. Monte Carlo (MC) simulation of internally-launched
      point source shows that the decrease of scattering coefficient of turbid medium,
      which can be achieved by optical tissue clearing approach, causes stronger peak
      intensity with a narrower full-width at half-maximum (FWHM). The improvement
      becomes more significant with the source depth increasing from 1 to 5 mm. The
      experimental results shows that tissue clearing with 50% glycerol solution could
      largely improve the brightness and the spatial resolution of CL imaging when the
      target is covered by biological tissue with a thickness of either 1 or 3mm. This
      method could have potential applications for the in vivo low-level light imaging
      techniques.

PMID- 15494227
TI  - In-line assessment of pulmonary drug delivery using light obscuration.
AB  - A candidate optical technology for characterisation of the value and quality of
      the drug dose delivered to a patient from an inhaler is examined. The theoretical
      reasoning behind the design of this technology is presented with reference to the
      optical scattering of the drug cloud. A technical implementation is presented;
      based upon the light obscuration signature, observed in the delivery path during
      drug delivery. Dose evaluation studies are reported, performed on different types
      of drug formulations using regulatory testing procedures and the proposed optical
      sensing system. Further applications of this technology are discussed in relation
      to the identification and evaluation of inhaler-drug formulation combinations,
      which are most suitable for particular patients.

PMID- 15494228
TI  - Enhancement of the multi-channel continuous monitoring system through the use of
      Xenorhabdus luminescens lux fusions.
AB  - The enhancement of the multi-channel continuous toxicity monitoring system
      developed previously was studied. To achieve better and more stable results from
      the system, the use of thermo-lux fusion strains that express the luxCDABE genes
      from Xenorhabdus luminescens was evaluated. A total of six recombinant
      Escherichia coli strains with the promoters from three oxidative-stress
      responsive genes, i.e. the katG, sodA and pqi-5 genes, fused to either the lux
      genes from Vibrio fischeri or X. luminescens were characterized and their
      responses to different chemicals compared. It was found that the basal level
      bioluminescence (BL) from the thermo-lux fusion strains was always higher while
      that of the V. fischeri lux strains were always near or below the lower limit of
      detection of the system. For example, the katG::V. fischeri lux strain, DPD2511,
      gave no discernible response due to its low level expression while a fusion of
      the katG promoter with the X. luminescens lux operon was clearly responsive and
      capable of detecting hydrogen peroxide down to about 1 ppm. The use of the thermo
      lux strains found them to be as sensitive as the V. fischeri lux strains while
      providing a brighter, more stable basal level bioluminescence, making the
      analysis and monitoring of water-borne toxicity more reliable.

PMID- 15494229
TI  - Telemetric electrochemical sensor.
AB  - A telemetric system was designed and constructed to sense pH and ethanol
      variation in aqueous solutions. The measured signals were transferred by software
      digitally and transmitted wirelessly by the telemeter, personal digital assistant
      (PDA), through the General Packet Radio Service (GPRS) protocol. The pH sensing
      electrode was designed to measure a chemical potential induced by a proton
      concentration gradient on the electrode's surface which exhibits internal Donnon
      diffusion behavior, and a linear relationship between the electrical potential
      and pH was found. The result shows that the wireless sensing system allowed not
      only long-term usage and long-distance transmission but also with high accuracy
      (e.g. S.D. less than +/-2%). The telemetric system can also be modified to
      measure ethanol concentration in aqueous solution amperometrically. It was found
      that the sensitivity of that ex situ measurements matched those of in field
      measurements with negligible deviation, less than 4%.

PMID- 15494230
TI  - Performance evaluation of salivary amylase activity monitor.
AB  - In order to quantify psychological stress and to distinguish eustress and
      distress, we have been investigating the establishment of a method that can
      quantify salivary amylase activity (SMA). Salivary glands not only act as
      amplifiers of a low level of norepinephrine, but also respond more quickly and
      sensitively to psychological stress than cortisol levels. Moreover, the time
      course changes of the salivary amylase activity have a possibility to distinguish
      eustress and distress. Thus, salivary amylase activity can be utilized as an
      excellent index for psychological stress. However, in dry chemistry system, a
      method for quantification of the enzymatic activity still needs to be established
      that can provide with sufficient substrate in a testing tape as well as can
      control enzymatic reaction time. Moreover, it is necessary to develop a method
      that has the advantages of using saliva, such as ease of collection, rapidity of
      response, and able to use at any time. In order to establish an easy method to
      monitor the salivary amylase activity, a salivary transcription device was
      fabricated to control the enzymatic reaction time. A fabricated salivary amylase
      activity monitor consisted of three devices, the salivary transcription device, a
      testing-strip and an optical analyzer. By adding maltose as a competitive
      inhibitor to a substrate Ga1-G2-CNP, a broad-range activity testing-strip was
      fabricated that could measure the salivary amylase activity with a range of 0-200
      kU/l within 150 s. The calibration curve of the monitor for the salivary amylase
      activity showed R2=0.941, indicating that it was possible to use this monitor for
      the analysis of the salivary amylase activity without the need to determine the
      salivary volume quantitatively. In order to evaluate the assay variability of the
      monitor, salivary amylase activity was measured using Kraepelin psychodiagnostic
      test as a psychological stressor. A significant difference of salivary amylase
      activity was recognized between the pre-stress and mid-stress periods. This study
      demonstrated that broad-range salivary amylase activity monitor was developed
      that could be used with only 5 microl of saliva.

PMID- 15494231
TI  - Utilizing adsorbed proteoliposomes trapped in a non-ruptured state on SiO2 for
      amplified detection of membrane proteins.
AB  - The quartz crystal microbalance with dissipation (QCM-D) technique was used to
      monitor the formation of supported phospholipid bilayers (SPBs) on SiO2 using
      proteoliposomes with reconstituted proton translocating nicotinamide nucleotide
      transhydrogenase (TH). Exposure of the surface to such proteoliposomes creates a
      lipid film composed of a mixture of proteolipid bilayers and adsorbed non
      ruptured proteoliposomes, where the fraction of the latter is reduced if the TH
      liposomes are pretreated with trypsin to remove the water soluble domains of TH
      [Langmuir 19 (2003) 842]. In the present work, the latter study is complemented
      by investigating the influence of trypsin treatment of the mixed adlayer
      (proteolipid bilayer + non-ruptured proteoliposomes) after adsorption on the
      surface. This demonstrates how trypsin-cleavage induced rupture of adsorbed TH
      liposomes can be utilized to detect the presence of less than 0.04 pmol/cm2 of
      immobilized TH.

PMID- 15494232
TI  - Amperometric measurements of nitric oxide in erythrocytes.
AB  - In the recent years, there has been an increase in the development of new
      biosensors that could be helpful in the study of various physiological processes.
      In this study, we report the development of a new in vitro experimental design
      for real-time nitric oxide (NO) amperometric measurements in erythrocyte
      suspensions. To achieve this, we employed human erythrocyte suspensions in sodium
      chloride 0.9%, pH 7 (haematocrit 0.05%). The production of NO by erythrocytes was
      measured with a commercial NO sensor during stimulation by L-arginine,
      acetylcholine, choline, atropine and velnacrine maleate (10 microM of final
      concentrations). We also measured the nitrite and nitrate concentrations produced
      by erythrocyte suspensions stimulated with the above effectors by means of the
      Griess reaction method. We observed that there was a direct relation between the
      electric current produced by the NO sensor, and the NO standard concentrations,
      thereby leading to a good calibration curve. The in vitro erythrocytes produced
      significant amperometric NO values in response to a wide range of effectors and
      these results have the same variation profile of the nitrites and nitrates
      results achieved with the Griess method. In conclusion, the amperometric NO
      sensor constitutes a reliable method for direct, and real-time measurement in
      vitro of the NO production of erythrocyte suspensions, As such, it offers a
      potential diagnostic technique for the evaluation of diseases, and the
      therapeutic progression of diseases, related to intracellular NO metabolism.

PMID- 15494233
TI  - Silicon chip-based patch-clamp electrodes integrated with PDMS microfluidics.
AB  - We report on a silicon wafer-based device that can be used for recording
      macroscopic ion channel protein activities across a diverse group of cell-types.
      Gigaohm seals were achieved for CHO-K1 and RIN m5F cells, and both cell-attached
      and whole-cell mode configurations were also demonstrated. Two distinct intrinsic
      potassium ion channels were recorded in whole-cell mode for HIT-T15 and RAW 264.7
      cells. Polydimethylsiloxane (PDMS) microfluidics were also coupled with the
      micromachined silicon chips in order to demonstrate that a single cell could be
      selectively directed to a micropore, and membrane protein currents could
      subsequently be recorded. These silicon chip-based devices have significant
      advantages over traditional micropipette approaches, and may serve as
      combinatorial tools for investigating membrane biophysics, pharmaceutical
      screening, and other bio-sensing tasks.

PMID- 15494234
TI  - Biocompatible glucose sensor prepared by modifying protein and vinylferrocene
      monomer composite membrane.
AB  - This paper proposes a very simple procedure for preparing a biocompatible sensor
      based on a protein (bovine serum albumin, BSA), enzyme and vinylferrocene (VF)
      composite membrane modified electrode. The membrane was prepared simply by first
      casting vinylferrocene and then coating it with BSA and glucose oxidase
      immobilised with glutaraldehyde. The sensor response was independent of dissolved
      oxygen concentration from 3 to 10 ppm and showed good stability for serum sample
      measurement, unlike the commonly used BSA/enzyme modified electrode. The sensor
      response was almost unchanged over the measurement time (>10 h) whereas the
      responses of a BSA and glucose oxidase modified platinum electrode and an osmium
      polyvinylpyridine wired horseradish peroxidase modified electrode (Ohara et al.,
      1993) fell to 68% of their initial value in a serum sample containing 10mM
      glucose.

PMID- 15494235
TI  - MICREDOX--development of a ferricyanide-mediated rapid biochemical oxygen demand
      method using an immobilised Proteus vulgaris biocomponent.
AB  - Biochemical oxygen demand (BOD) is an international regulatory environmental
      index for monitoring organic pollutants in wastewater and the current legislated
      standard test for BOD monitoring requires 5 days to complete (BOD5 test). We are
      developing a rapid microbial technique, MICREDOX, for measuring BOD by
      eliminating oxygen and, instead, quantifying an equivalent biochemical co
      substrate demand, the co-substrate being a redox mediator. Elevated
      concentrations of Proteus vulgaris, either as free cells or immobilised in
      Lentikat disks, were incubated with an excess of redox mediator (potassium
      hexacyanoferrate(III)) and organic substrate for 1h at 37 degrees C without
      oxygen. The addition of substrate increased the catabolic activity of the
      microorganisms and the accumulation of reduced mediator, which was subsequently
      re-oxidised at a working electrode generating a current quantifiable by a
      coulometric transducer. The recorded currents were converted to their BOD5
      equivalent with the only assumption being a fixed conversion of substrate and
      known stoichiometry. Measurements are reported both for the BOD5 calibration
      standard solution (150 mg l(-1) glucose, 150 mg l(-1) glutamic acid) and for
      filtered effluent sampled from a wastewater treatment plant. The inclusion of a
      highly soluble mediator in place of oxygen facilitated a high ferricyanide
      concentration in the incubation, which in turn permitted increased concentrations
      of microorganisms to be used. This substantially reduced the incubation time,
      from 5 days to 1h, for the biological oxidation of substrates equivalent to those
      observed using the standard BOD5 test. Stoichiometric conversion efficiencies for
      the oxidation of the standard substrate by P. vulgaris were typically 60% for
      free cells and 35-50% for immobilised cells.

PMID- 15494236
TI  - A new film for the fabrication of an unmediated H2O2 biosensor.
AB  - A novel and stable film made from polyethylene glycol (PEG) on pyrolytic graphite
      (PG) electrode was presented in this paper for incorporating horseradish
      peroxidase (HRP) to study the direct electrochemistry of the enzyme. In PEG film,
      HRP showed a thin-layer electrochemistry behavior. The apparent standard
      potential (E degrees ') was -0.379 V versus SCE at pH 7.2. Moreover, the PEG-HRP
      modified electrode exhibited excellent electrocatalytical response to the
      reduction of H2O2 with a calibration range between 2.0 x 10(-6) and 6.0 x 10(-4)
      M and a good linear relation from 2.0 x 10(-6) to 1.0 x 10(-4) M, on which an
      unmediated H2O2 biosensor was based. The detection limit of 6.7 x 10(-7) M was
      estimated when the signal-to-noise ratio was 3. The relative standard deviation
      (R.S.D.) was 4.7% for six successive determinations at a concentration of 4.0 x
      10(-5) M. The apparent Michaelis-Menten constant (Km app) of the sensor was found
      to be 1.38 mM. Epinephrine, dopamine, and ascorbic acid did not interfere with
      the sensitive determination of H2O2.

PMID- 15494237
TI  - Detection of Mycobacterium tuberculosis (TB) in vitro and in situ using an
      electronic nose in combination with a neural network system.
AB  - The use of volatile production patterns produced by Mycobacterium tuberculosis
      and associated bacterial infections from sputum samples were examined in vitro
      and in situ using an electronic nose based on a 14 sensor conducting polymer
      array. In vitro, it was possible to successfully discriminate between M.
      tuberculosis (TB) and control media, and between M. tuberculosis and M. avium, M.
      scrofulaceum and Pseudomonas aeruginosa cultures in the stationary phase after 5
      6h incubation at 37 degrees C based on 35 samples. Using neural network (NN)
      analysis and cross-validation it was possible to successfully identify 100% of
      the TB cultures from others. A second in vitro study with 61 samples all four
      groups were successfully discriminated with 14 of 15 unknowns within each of the
      four groups successfully identified using cross-validation and discriminant
      function analysis. Subsequently, lipase enzymes were added to 46 sputum samples
      directly obtained from patients and the head space analysed. Parallel
      measurements of bacterial contamination were also carried out for confirmation
      using agar media. NN analysis was carried out using some of the samples as a
      training set. Based on the NN and genetic algorithms of up to 10 generations it
      was possible to successfully cross-validate 9 of 10 unknown samples. PCA was able
      to discriminate between TB infection alone, the controls, M. avium, P. aeruginosa
      and a mixed infection. These findings will have significant implications for the
      development of rapid qualitative systems for screening of patient samples and
      clinical diagnosis of tuberculosis.

PMID- 15494238
TI  - Molecular assembly of redox-conductive ferrocene-streptavidin conjugates--towards
      bio-electrochemical devices.
AB  - Peptidic spacers, 0.4 and 2 nm in length, were used to couple ferrocene moieties
      to streptavidin. The resulting conjugates were immobilised on electrode surfaces
      using biotin binding. The electron transfer through multilayers of the conjugates
      is strongly dependent on the length of the spacer between the protein and the
      attached ferrocene. A monolayer of the long-linker conjugate immobilised on
      interdigitated microelectrode arrays was found to electrochemically bridge the 2
      microm wide non-conductive gap between the electrodes. The redox current through
      the layer is dependent on external parameters such as the applied voltage
      difference between the two electrode arrays or the temperature. The long-range
      electrochemical conductivity in combination with the biotin binding capability is
      a prerequisite for the application of the conjugates in future bio
      electrochemical devices.

PMID- 15494239
TI  - Measurement of film thickness up to several hundreds of nanometers using optical
      waveguide lightmode spectroscopy.
AB  - Up to now, most studies based on optical waveguide lightmode spectroscopy (OWLS)
      were dedicated to thin adlayers, assumed to be isotropic and homogeneous, for
      which data analysis was based on an approximation of the mode equations valid
      when the thickness is small with respect to the wavelength of the laser light.
      The aim of the present paper is to extend the use of OWLS to thicker deposited
      layers (up to approximately 400 nm). Both the simplified and extended models are
      compared in terms of optical parameters, i.e. the refractive index nA, the
      thickness dA, and the optical mass QA, for experimental data obtained with
      polyelectrolyte multilayer films. The deviation of these parameters can be quite
      large when derived using the simplified model instead of the extended model. This
      observation evidences that OWLS is well suited for the study of "thick" films if
      the appropriate model is applied to the data analysis.

PMID- 15494240
TI  - Short-term BOD (BODst) as a parameter for on-line monitoring of biological
      treatment process. Part I. A novel design of BOD biosensor for easy renewal of
      bio-receptor.
AB  - A novel design of a biochemical oxygen demand (BOD) biosensor has been developed
      for on-line monitoring of easily biodegradable organic compounds in aqueous
      samples. The biological recognition element of the sensor could be easily renewed
      by injecting new bacterial paste without disassembling the sensor system. The
      sensor measurements were carried out in the initial-rate mode using a flow
      injection (FI) system, resulting in 60 s for one sample analysis followed by a
      recovery time less than 10 min. The sensor performance achieved showed a wide
      detection linearity over the range of 5-700 mg BOD5.l(-1) and a generally good
      agreement between the BOD values estimated by the biosensor and the conventional
      5-day test. Furthermore, the precision test was in the control range (i.e.
      repeatability < or = /+/-7.5%/, reproducibility < or = /+/-7.3%/). The sensor
      could be used over 1 week in continuous test, however, the best performance was
      found within the first 24 h where standard deviation of the sensor response was
      +/-2.4%. The design of the sensor allows easy and fast renewal of the cells used
      as sensing elements. Replacement of biological recognition element and
      calibration of the sensor responses can be performed in a rather simple procedure
      on a daily regular basis. By using a mixed culture as the bio-receptor, one gets
      a sensor that reacts to a wide range of substrates. The new sensor construction
      will thus allow fast and convenient replacement of the bio-receptor and on-line
      assay of a broad range of substrates. This makes the sensor being an interesting
      and promising candidate for on-line monitoring of biological treatment process.

PMID- 15494241
TI  - Short-term BOD (BODst) as a parameter for on-line monitoring of biological
      treatment process; Part II: instrumentation of integrated flow injection analysis
      (FIA) system for BODst estimation.
AB  - An instrument with integrated flow injection analysis (FIA) system has been
      developed for on-line monitoring a process for conversion of biomass under field
      condition. The instrument consists of a newly designed biosensor for easy renewal
      of the bio-receptor without disassembling the sensor, a FIA controller for
      controlling the analysis operations, and a computer-based data acquisition system
      for data recording and processing. The instrument performed a sequence operations
      automatically including preparation of sample in the desired concentration,
      sample loading, sample injection, signal recording, data processing, and self
      cleaning of the system. This makes the instrument being an interesting and
      promising device for on-line process monitoring.

PMID- 15494242
TI  - Single-wall carbon nanotube-based voltammetric sensor and biosensor.
AB  - The pH-sensitive property of the single-wall carbon nanotube modified electrode
      based on the electroactive group on the single-wall carbon nanotube was explored
      by differential pulse voltammetry technique. In pH range 1-13 investigated in
      Britton-Robinson (B-R) buffer, the anodic peak shifted negatively along with the
      increase of pH exhibiting a reversible Nernstian response. Experiments were
      carried out to investigate the response of the single-wall carbon nanotube (SWNT)
      modified electrode to analytes associated with pH change. The response behavior
      of the modified electrode to ammonia was studied as an example. The potential
      response could reach equilibrium within 5 min. The modified electrode had good
      operational stability. Voltammetric urease and acetylcholinesterase biosensors
      were constructed by immobilizing the enzymes with sol-gel hybrid material. The
      maximum potential shift could reach 0.130 and 0.220 V for urea and
      acetylthiocholine, respectively. The methods for preparing sensor and biosensor
      were simple and reproducible and the range of analytes could be extended to
      substrates of other hydrolyases and esterases. This broadened the biosensor
      application of carbon nanotube in electrochemical area.

PMID- 15494243
TI  - A staphylococcal enterotoxin B magnetoelastic immunosensor.
AB  - A magnetoelastic immunosensor for detection of staphylococcal enterotoxin B (SEB)
      is described. The magnetoelastic sensor is a newly developed mass/elasticity
      based transducer of high sensitivity having a material cost of approximately
      $0.001/sensor. Affinity-purified rabbit anti-SEB antibody was covalently
      immobilized on magnetoelastic sensors, of dimensions 6 mm x 2 mm x 28 microm. The
      affinity reaction of biotin-avidin and biocatalytic precipitation are used to
      amplify antigen-antibody binding events on the sensor surface. Horseradish
      peroxidase (HRP) and alkaline phosphatase were examined as the labeled enzymes to
      induce biocatalytic precipitation. The alkaline phosphatase substrate, 5-bromo-4
      chloro-3-indolyl phosphate (BCIP) produces a dimer, which binds tightly to the
      sensor surface, inducing a change in sensor resonance frequency. The biosensor
      demonstrates a linear shift in resonance frequency with staphylococcal
      enterotoxin B concentration between 0.5 and 5 ng/ml, with a detection limit of
      0.5 ng/ml.

PMID- 15494244
TI  - Evaluation of a new biosensor-based mushroom (Agaricus bisporus) tissue
      homogenate: investigation of certain phenolic compounds and some inhibitor
      effects.
AB  - A biosensor based on mushroom tissue homogenate for detecting some phenolic
      compounds (PCs) and usage of the biosensor for quantifying certain substances
      that inhibit the polyphenol oxidase activity in mushroom (Agaricus bisporus)
      tissue homogenate is described. The mushroom tissue homogenate was immobilized to
      the top of a Clark-type oxygen electrode with gelatin and glutaraldehyde.
      Optimization of the experimental parameters was done by buffer system, pH, buffer
      concentration, and temperature. Besides, the detection range of eight phenolic
      compounds were obtained with the help of the calibration graphs. Thermal
      stability, storage stability, and repeatability of the biosensor were also
      investigated. A linear response was observed from 20 x 10(-3) to 200 x 10(-3) mM
      phenol. The biosensor retained approximately 74% of its original activity after
      25 days of storage at 4 degrees C. In repeatability studies, variation
      coefficient (C.V.) and standard deviation (S.D.) were calculated as 2.44% and +/
      0.002, respectively. Inhibition studies revealed that the proposed biosensor was
      applicable for monitoring benzoic acid and thiourea in soft drinks and fruit
      juices.

PMID- 15494245
TI  - A new approach for the detection of DNA sequences in amplified nucleic acids by a
      surface plasmon resonance biosensor.
AB  - In this paper, a simple and useful approach for DNA sensing based on surface
      plasmon resonance (SPR) transduction is reported. A new DNA sample pre-treatment
      has been optimised to allow fast and simple detection of hybridisation reaction
      between a target sequence in solution and a probe immobilised on the sensing
      surface. This pre-treatment consisted in a denaturation procedure of double
      stranded DNA containing the target sequence and was based on an high temperature
      treatment (95 degrees C, 5 min) followed by a 1 min incubation with small
      oligonucleotides. The oligonucleotides are designed to prevent the re-hybridising
      of the denatured strands, while enabling the target sequence to bind the
      immobilised probe. The important parameters of the procedure, i.e. incubation
      time, length and concentration of the oligonucleotides, have been studied in
      detail. The optimised DNA denaturation procedure has been successfully applied to
      the detection of amplified DNA with a commercially available SPR biosensor
      (Biacore X). DNA samples extracted from plant and human blood were tested after
      amplification by polymerase chain reaction (PCR).

PMID- 15494246
TI  - Electronic manipulation of DNA, proteins, and nanoparticles for potential circuit
      assembly.
AB  - Using gold electrodes lithographically fabricated onto microscope cover slips,
      DNA and proteins are interrogated both optically (through fluorescence) and
      electronically (through conductance measurements). Dielectrophoresis is used to
      position the DNA and proteins at well-defined positions on a chip. Quadrupole
      electrode geometries are investigated with gaps ranging from 3 to 100 microm;
      field strengths are typically 10(6) V/m. Twenty nanometer latex beads are also
      manipulated. The electrical resistance of the electronically manipulated DNA and
      proteins is measured to be larger than 40 MOhms under the experimental conditions
      used. The technique of simultaneously measuring resistance while using
      dielectrophoresis to trap nanoscale objects should find broad applicability.

PMID- 15494247
TI  - Development of an amperometric biosensing method for the determination of L
      fucose in pretreated urine.
AB  - The first amperometric biosensing method for the determination of L-fucose is
      described. L-Fucose is the objective of much current research, as it is
      considered as a potential marker for various pathologic disorders. Recombinant L
      fucose dehydrogenase, having as cofactor beta-nicotinamide adenine dinucleotide
      phosphate (NAD+P), was cross-linked in a water-soluble photosensitive polymer
      matrix, that is, polyvinyl alcohol (PVA) modified with styrylpyridinium (SbQ), in
      the presence of BSA and glutaraldehyde. The resulting membrane was sandwiched
      between two polycarbonate membranes and was mounted in an amperometric cell. The
      oxidation of the enzymatically produced NADPH was monitored at a platinum anode
      at +0.25 V versus a silver pseudoreference electrode in the presence of
      ferricyanide. The system was fully optimized with respect to various analytical
      parameters. Regarding to the mechanical properties of the membrane and the
      storage stability of the immobilized enzyme, various parameters were also
      optimized. Several methods for the pretreatment of urine samples were
      investigated. Treatment of the samples with PbO2 found to eliminate the
      interference effect of various electroactive species exist in urine; optimum
      incubation time was determined since at prolonged incubation times L-fucose is
      also affected. Calibration curves for the direct and the mediated monitoring of
      NADPH were liner over the concentration ranges 0.04-1.0 mM (r2=0.9995) and 0.03
      3.0 mM (r2=0.9997) fucose, respectively. The detection limits (S/N 3) were 2 and
      1.5 microM fucose, respectively. The R.S.D. of the mediated biosensor is better
      than 1.5% (n=10, 0.5 mM fucose). The proposed biosensor correlates well with a
      reference enzymatic method and exhibits very good working and storage stability.

PMID- 15494248
TI  - Sorting out molecules reacting with acetylcholinesterase by enzyme encapsulation
      in liposome.
AB  - Enzymes are considered as providential molecules for biosensor design because of
      their sensitivity and the high specificity of the reactions they catalyse.
      However, their active sites often display low selectivity, a lot of molecules may
      enter and interfere with catalysis. These molecules may be either competitive
      inhibitors, activators or molecules which change the physico-chemical environment
      of the enzyme (pH, ionic strength). They produce the "matrix effect" that lowers
      the reliability of biosensors. We show here that encapsulation of enzymes in
      liposomes inserts a barrier between the enzyme and the external environment and
      protects the enzyme in a stable nano-environment for an optimal activity. This
      barrier sorts out the molecules that could react with the enzyme according to
      their hydrophobicity. Acetylcholinesterase is used to detect organophosphorous
      and carbamate insecticide residues but several molecules (reversible inhibitors,
      pH and ionic strength modifiers) generate matrix effects in free conditions.
      These perturbations were completely ineffective following enzyme encapsulation.

PMID- 15494249
TI  - A sensitivity comparison of optical biosensors based on four different surface
      plasmon resonance modes.
AB  - Current surface plasmon resonance (SPR) modes based on the attenuated total
      reflection (ATR) method can broadly be categorized as: conventional SPR, long
      range SPR (LRSPR), coupled plasmon-waveguide resonance (CPWR), and waveguide
      coupled SPR (WCSPR). Although the features of optical biosensors are dependent
      upon their particular SPR mode, a common requirement for all biosensors utilized
      for biomolecular interaction analysis (BIA) is a high degree of sensitivity. The
      current paper presents a theoretical analysis and comparison of the sensitivity
      and resolution of these four types of SPR biosensors when employed in three of
      the most prevalent detection methods, namely angular interrogation, wavelength
      interrogation, and intensity measurement. This study develops a detailed
      understanding of the influences of various biosensor design parameters in order
      to enhance the sensitivity and detection limit capabilities of such devices.

PMID- 15494250
TI  - Metabolic imaging of tumors using intrinsic and extrinsic fluorescent markers.
AB  - One of the biochemical "hallmarks" of malignancy is enhanced tumor glycolysis,
      which is primary due to the overexpression of glucose transporters (GLUTs) and
      the increased activity of mitochondria-bound hexokinase in tumors. Easy methods
      for assessing glucose utilization in vitro and in vivo should find widespread
      application in biological and biomedical studies, as illustrated by the adoption
      of FDG PET imaging in medicine. We have recently synthesized a new NIR
      fluorescent pyropheophorbide conjugate of 2-deoxyglucose (2DG), Pyro-2DG, as a
      GLUT-targeted photosensitizer. In this study, we have evaluated the in vivo
      uptake of Pyro-2DG and found that Pyro-2DG selectively accumulated in two tumor
      models, 9L glioma in the rat and c-MYC-induced mammary tumor in the mouse,
      compared to surrounding normal muscle tissues at a ratio of about 10:1. By
      simultaneously performing redox ratio and fluorescence imaging, a high degree of
      correlation between the PN/(Fp+PN) redox ratio, where PN denotes reduced pyridine
      nucleotides (NADH) and Fp denotes oxidized flavoproteins, and the Pyro-2DG uptake
      was found in both murine tumor models, indicating that Pyro-2DG could serve as an
      extrinsic NIR fluorescent metabolic index for the tumors. The fact that only a
      low level of correlation was observed between the redox ratio and the uptake of
      Pyro-acid (the free fluorophore without the 2-deoxyglucose moiety) supports the
      hypothesis that Pyro-2DG is an index of the mitochondrial status (extent of PN
      reduction) of a tumor.

PMID- 15494251
TI  - Lactose biosensor based on Langmuir-Blodgett films of poly(3-hexyl thiophene).
AB  - An amperometric lactose biosensor was developed by immobilizing lactase (EC
      3.2.1.23) and galactose oxidase (GaO) (EC 1.1.3.9) in Langmuir-Blodgett (LB)
      films of poly(3-hexyl thiophene) (P3HT)/stearic acid (SA) for estimation of
      lactose in milk and its products to prevent "lactose intolerance". The enzyme
      immobilized LB film was used as working electrode and platinum as reference
      electrode. The enzyme electrodes show a linearity 1-6 g/dL of lactose and have a
      shelf life more than 120 days. The reusability of electrode was found ten times
      with 3% loss in current response. The enzyme electrode was characterized by
      Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy
      (SEM) and kinetic parameters such as pH, temperature and stability. The working
      electrode may be used for the estimation of lactose/galactose in food and
      biological fluids.

PMID- 15494252
TI  - Label-free amplified bioaffinity detection using terahertz wave technology.
AB  - A new affinity biosensor based on pulsed terahertz (THz) wave technology has been
      used to monitor binding between biotin and avidin molecules. Amplified detection
      of avidin-biotin binding is obtained on supported membranes composed of biotin
      layers on quartz surface, which is modified with octadecanol. Agarose particles
      are conjugated with avidin and then applied to biotin, which is already bound to
      the octadecanol quartz surface, the biotin binds to the conjugate rapidly and
      causes an enhancement of the THz difference signal between biotin and biotin
      avidin complexes by a factor greater than eight fold when compared to the same
      sample without agarose beads. The technique was able to detect less than 10.3
      ng/cm2 avidin, thus, giving the THz system a detection capability of sub-thin
      solid films better than ellipsometry and reflectometry techniques. Further
      improvement is underway using highly refractive beads together with appropriate
      surface chemistry. This newly developed method is being saliently optimized for
      future application, including the detection of DNA hybridization and ligand
      analyte affinity binding.

PMID- 15494253
TI  - Healthcare worker safety is a pre-requisite for injection safety in developing
      countries.
AB  - Unsafe injection practices, including the re-use of unsterile needles and
      syringes, are commonplace in developing country health settings, and contribute
      substantially to the global burden of blood-borne viral disease. Unsafe injection
      practices place at risk not only patients, but also healthcare workers, who
      practice universal precautions inconsistently and are commonly exposed to blood
      in the course of their work. Global awareness of the link between unsafe
      injection practices and the burden of blood-borne viral disease was slow to
      emerge but has grown in the recent years. In 1999, the World Health Organization
      (WHO) established the Safe Injection Global Network (SIGN), which advocates a
      range of interventions for the promotion of injection safety. As well as
      exhorting healthcare workers to use a new needle and syringe for every injection,
      they should also be encouraged and supported to protect themselves from exposure
      to blood. It is argued here that promoting the occupational safety of healthcare
      workers in developing countries is an essential and currently under-valued
      component of the response to the problem of unsafe injection practices.
      Protecting healthcare workers from occupational infection with blood-borne
      viruses has a range of potential benefits, including safer injection practices
      for patients and less discrimination against people with HIV/AIDS. There is an
      urgent need for organisational commitment to the occupational safety of
      healthcare workers in developing countries, along with the provision of training
      in injection safety and universal precautions, adequate supplies of personal
      protective equipment, and hepatitis B vaccination.

PMID- 15494254
TI  - Vaccines administered simultaneously: directions for new combination vaccines
      based on an historical review of the literature.
AB  - OBJECTIVES: The recognized benefits of administering vaccines simultaneously has
      encouraged vaccine producers to develop combination vaccines. If contemporary
      research and development can realize vaccines that achieve the current standards
      for safety, immunogenicity, and efficacy, other specific vaccine associations may
      also merit reconsideration as combination vaccines. METHODS: An historical review
      of the vaccine association literature reveals two important themes: first, the
      programs of mass vaccination, in particular, the eradication of smallpox,
      sessions where multiple vaccines (other than the smallpox vaccine) were given
      concurrently, and the Expanded Programme on Immunization (EPI); and, second, the
      domain of travel vaccines, including travellers to a disease-endemic country
      (such as migrants, tourists, military personnel, or expatriates) and WHO
      requirements for international travellers. RESULTS/CONCLUSIONS: Based on this
      historical review, combination vaccines worth reconsideration could fill
      epidemiologic niches in the EPI with, for instance, a measles--yellow fever, a
      measles--Japanese encephalitis or a pertussis-based paediatric combination rabies
      vaccine. Furthermore, other combinations could broaden protection against the
      pathogens responsible for meningitis, pneumonia, or enteric diseases.
      Nevertheless, complex issues such as necessity, feasibility, or affordability
      will ultimately determine if any one of these becomes a combination vaccine.

PMID- 15494255
TI  - Rapid diagnosis of rabies in humans and animals by a dot blot enzyme immunoassay.
AB  - OBJECTIVES: The presently advocated tests for rapid diagnosis of rabies, such as
      the fluorescent antibody test (FAT) are expensive and require expertise to carry
      out and interpret the results. In this study, a simple direct dot blot enzyme
      immunoassay (DIA) has been developed and evaluated to detect the rabies antigen
      in brain specimens of animals and humans. The utility of this test in the ante
      mortem diagnosis of human rabies has also been evaluated. METHODS: Brain
      homogenates of suspected rabid animals (n = 250), humans (n = 16) and clinical
      samples like saliva (n = 12) and cerebrospinal fluid (CSF) (n = 12) were directly
      spotted on polyvinylidene difluoride membrane (PVDF) and the absorbed rabies
      nucleoprotein antigen was detected using biotinylated antinucleoprotein antibody
      followed by treatment with streptavidin peroxidase conjugate and color
      development with diamino benzedine (DAB). Rabies-infected and normal mouse brain
      homogenates were used as positive and negative controls, respectively. The
      results of this test were evaluated with fluorescent antibody technique (for
      brain samples) and mouse inoculation test (for saliva and CSF samples). RESULTS:
      A distinct dark brown color was seen in the positive control and all positive
      samples, while there was no color development with either the negative control or
      the negative samples. The concordance between the fluorescent antibody test (FAT)
      and dot immunoassay was 98.4% for brain samples, 83.3% for saliva and 91.6% for
      CSF samples. The specificity of the test was found to be 100%. CONCLUSIONS: The
      dot blot enzyme immunoassay (DIA) test described here is a sensitive, specific
      and rapid test for the post-mortem diagnosis of rabies in animals and humans. The
      utility of this test for the ante-mortem diagnosis of rabies needs to be further
      evaluated.

PMID- 15494256
TI  - Rabies deaths in Pakistan: results of ineffective post-exposure treatment.
AB  - OBJECTIVES: To estimate the incidence of rabies and the effectiveness of post
      exposure treatment (PET) in Pakistan. METHODS: Rabies cases admitted from July
      1993 to December 1994 to a public rabies isolation hospital were analyzed. Two
      samples (one sample each from a separate peripheral site) of a single batch of
      sheep brain vaccine (SBV) were also tested for potency by the National Institute
      of Health (NIH) test in May 1997. RESULTS: Forty patients were admitted with a
      history of clinical rabies. The median age was 22 years and 55% were under 15.
      Thirteen (23%) victims did not receive any vaccine; the remaining 27 (67%)
      received SBV only, and of these, 16 (40%) received a full course of SBV. No
      rabies immunoglobulins (RIG) or cell culture vaccines were administered. There
      were frequent power blackouts and no back-up supply at the public hospital. In
      house potency testing of the vaccine batch by the manufacturer was adequate,
      although it was not tested by the World Health Organization (WHO) recommended NIH
      test. Samples of SBV of the same batch collected at the peripheral sites showed
      no potency. Rabies incidence was estimated to range between 7.0 to 9.8 cases per
      million annually. CONCLUSION: A multi-sectorial approach is needed to decrease
      rabies incidence in Pakistan. Public and healthcare practitioner education on
      prompt and appropriate PET, especially the use of cost-effective cell culture
      intradermal regimens, is needed urgently. The NIH test should be employed for
      vaccine potency testing. An independent agency is needed for monitoring vaccine
      quality and strategies are needed for maintaining cold chain. SBV should be
      replaced by locally manufactured second-generation cell culture rabies vaccine.
      Purified equine rabies immunoglobulin (ERIG) should be manufactured locally to
      meet national needs. Furthermore, effective dog control strategies should be
      implemented to decrease the rabies reservoir.

PMID- 15494257
TI  - Routine lumbar puncture in children with febrile seizures in Ghana: should it
      continue?
AB  - OBJECTIVES: Performing routine lumbar punctures in children with febrile seizures
      has been controversial. This study aimed to determine the positive yield of
      lumbar punctures in a setting where routine lumbar puncture is routinely carried
      out and to determine if any other parameter could help differentiate bacterial
      meningitis from the various other diagnoses of children who presented with a
      febrile seizure. DESIGN: A prospective study was carried out among children aged
      three months to 15 years of age, hospitalized at the Komfo Anokye Teaching
      Hospital in Kumasi, Ghana, between July and August 2000. RESULTS: There was a
      10.2% (n = 19) positive yield for bacterial meningitis with a case fatality rate
      of 36.8% (n = 7). Cerebral malaria, which is not easily distinguishable from
      bacterial meningitis, accounted for 16.1% (n = 30) of the children. Twenty
      percent of bacterial meningitis patients had a positive blood smear for malaria.
      The indication for doing a lumbar puncture was similar in both cerebral malaria
      and bacterial meningitis patients. Signs of meningism were not the primary reason
      for carrying out a lumbar puncture, even in the group of children who had
      bacterial meningitis. CONCLUSION: Performing routine lumbar punctures may still
      have a role to play in the management of children with febrile seizures.

PMID- 15494258
TI  - Comparative in vitro activity of a pharmacokinetically enhanced oral formulation
      of amoxicillin/clavulanic acid (2000/125 mg twice daily) against 9172 respiratory
      isolates collected worldwide in 2000.
AB  - OBJECTIVES: A new, pharmacokinetically enhanced, oral formulation of
      amoxicillin/clavulanic acid has been developed to overcome resistance in the
      major bacterial respiratory pathogen Streptococcus pneumoniae, while maintaining
      excellent activity against Haemophilus influenzae and Moraxella catarrhalis,
      including beta-lactamase producing strains. This study was conducted to provide
      in vitro susceptibility data for amoxicillin/clavulanic acid and 16 comparator
      agents against the key respiratory tract pathogens. METHODS: Susceptibility
      testing was performed on 9172 isolates collected from 95 centers in North
      America, Europe, Australia, and Hong Kong by broth microdilution MIC
      determination, according to NCCLS methods, using amoxicillin/clavulanic acid and
      16 comparator antimicrobial agents. Results were interpreted according to NCCLS
      breakpoints and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints based on oral
      dosing regimens. RESULTS: Overall, 93.5% of Streptococcus pneumoniae isolates
      were susceptible to amoxicillin/clavulanic acid at the current susceptible
      breakpoint of < or =2 microg/mL and 97.3% at the PK/PD susceptible breakpoint of
      < or =4 microg/mL for the extended release formulation. Proportions of isolates
      that were penicillin intermediate and resistant were 13% and 16.5%, respectively,
      while 25% were macrolide resistant and 21.8% trimethoprim/sulfamethoxazole
      resistant. 21.9% of Haemophilus influenzae were beta-lactamase producers and
      16.8% trimethoprim/sulfamethoxazole resistant, >99% of isolates were susceptible
      to amoxicillin/clavulanic acid, cefixime, ciprofloxacin and levofloxacin at NCCLS
      breakpoints. The most active agents against Moraxella catarrhalis were
      amoxicillin/clavulanic acid, macrolides, cefixime, fluoroquinolones, and
      doxycycline. Overall, 13% of Streptococcus pyogenes were resistant to macrolides.
      CONCLUSION: The extended release formulation of amoxicillin/clavulanic acid has
      potential for empiric use against many respiratory tract infections worldwide due
      to its activity against species resistant to many agents currently in use.

PMID- 15494259
TI  - Simulated post-exposure rabies vaccination: comments on article by Madhusudana et
      al.

PMID- 15494261
TI  - Electrolyte disturbances may predispose nucleoside analogue-treated AIDS patients
      to acute renal failure.

PMID- 15494262
TI  - A case of intracranial abscess due to Brucella melitensis.

PMID- 15494263
TI  - Molecular diagnostics in virology.
AB  - Molecular biology has significantly improved diagnosis in the field of clinical
      virology. Virus discovery and rapid implementation of diagnostic tests for newly
      discovered viruses has strongly beneficiated from the development of molecular
      techniques. Viral load and antiviral resistance or subtyping assays are now part
      of the biological monitoring of patients chronically infected by human
      immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV)
      and CMV. It will be important to add to this panel assays for other viruses of
      the herpesviridae family. Qualitative assays for the detection of blood-borne
      viruses have increased safety of blood donation and organ transplantation.
      Screening of other blood-borne viruses (parvovirus B19, HAV), multiplexing of
      detection and test automation to improve practicability and reduce costs will be
      the next steps. A major evolution in the near future will be the generalization
      of NAT for the diagnosis of viral etiology in patients, mostly with respiratory,
      CNS or gastro-intestinal diseases. Major technical improvements have been made to
      avoid obstacles that still limit this generalization, i.e. genetic variability of
      viruses, multiplex detection, contamination risk. Commercial offers already exist
      but menus must be extended to limit the validation and documentation work
      associated with home-brew assays. Real-time amplification has allowed the
      development of new NAT platforms but automation and integration of all steps of
      the reaction are still required to reduce hands-on-time, time-to-result and
      costs, and to increase throughput.

PMID- 15494264
TI  - Characterization of species B adenoviruses isolated from fecal specimens taken
      from poliomyelitis-suspected cases.
AB  - BACKGROUND: Human adenoviruses are classified into six species, A-F, and 51
      serotypes are recognized. Adenoviruses can cause a broad range of diseases.
      Serotypes 3, 7 and 21 are most commonly associated with CNS disease. Serotype 21
      (specie B) was isolated from brain tissue and CSF of patients with acute flaccid
      paralysis (AFP) in Malaysia. OBJECTIVES: Characterize, by molecular methods,
      species B adenoviruses isolated from poliomyelitis-suspected cases and
      investigate the possible etiological role of adenoviruses in acute flaccid
      paralysis (AFP). STUDY DESIGN: 622 virus isolates, including Sabin-related
      polioviruses, non-polio enteroviruses (NPEV) and adenoviruses, were recovered
      from fecal specimens in our laboratory during the period of 1997-2002 from AFP
      cases occurring in Brazil, Peru and Bolivia. Negative controls consisted of 528
      fecal specimens collected from healthy children <==5 of age. Of these, 478 were
      contacts of AFP negative cases and 50 were from a day-care center. RESULTS: Sixty
      four adenovirus strains isolated in HEp2 (human laryngeal tumor cells) cells were
      confirmed as such by an adenovirus-group specific PCR. Nucleotide sequencing
      identified the following adenovirus species: A (3 isolates), B (20 isolates), C
      (38 isolates), D (2 isolates) and E (1 isolate). The following serotypes
      belonging to the species B were identified: Ad3 (1 strain), Ad7 (17 strains) and,
      Ad16 (2 strains). CONCLUSION: Other viral agents became more recognized in
      association with CNS diseases in areas where wild polioviruses have been
      eradicated. The possible role of species B adenoviruses in the etiology of AFP
      cases similar to that caused by wild poliovirus is discussed.

PMID- 15494265
TI  - HCV genotype 4--an emerging threat as a cause of chronic liver disease in Indian
      (south) patients.
AB  - BACKGROUND: Hepatitis C virus (HCV) genotyping is relevant for the delivery of
      effective antiviral therapy. HCV genotypes are geographically restricted with
      genotype 4, which is resistant to therapy, traditionally considered to be
      confined to the Middle East and Africa. We report here on the occurrence of HCV
      genotype 4 in Indian (South) patients. OBJECTIVES: 1) To highlight the occurrence
      of HCV genotype 4 in the patient population attending a tertiary care hospital in
      south India. 2) To ascertain the difference in HCV viral loads and alanine
      aminotransferase (ALT) values between patients infected with HCV genotype 4 and
      those infected with the other two most commonly detected genotypes in this
      patient population viz., HCV genotypes 1 and 3. 3) To assess the genetic
      relatedness of the Indian strains to Genbank sequences, which we report for the
      first time. STUDY DESIGN: The study group consisted of 125 HCV infected,
      untreated patients who had been genotyped using type specific primers. Eight of
      the nine samples classified as HCV genotype 4 by this technique were subjected to
      nucleotide sequencing. Viral load estimations were carried out. Information on
      possible risk factors and ALT values were obtained from hospital records.
      Statistical analyses were carried out to compare viral loads and ALT values
      across genotypes. A phylogenetic tree was constructed and the genetic relatedness
      of the strains was assessed through sequence analysis. RESULTS: HCV genotype 4
      was detected in nine of 125 (7.2%) patients. Eight of the nine were subjected to
      nucleotide sequencing and all strains were confirmed as HCV genotype 4. Six of
      the eight strains were closely related, with two strains being phylogenetically
      diverse. CONCLUSIONS: HCV genotype 4 is detected in a significant minority of HCV
      infected patients in India. This finding should be considered in designing
      strategies prior to initiation of therapy in Indian patients infected with HCV.

PMID- 15494266
TI  - Rotavirus genotyping: keeping up with an evolving population of human
      rotaviruses.
AB  - The use of molecular methods for rotavirus characterisation provides not only
      increased sensitivity for typing, but also allows accurate and more complete
      characterisation of strains, and the identification of putative reassortant
      strains. However, due to the constant accumulation of point mutations through
      genetic drift, and to the emergence of novel genotypes, possibly zoonotic
      transmission and subsequent reassortment, the reagents and methods used require
      close monitoring and updating. Methods and oligonucleotide primers are described
      to overcome failures to type G9, G10 and P[11] rotavirus strains, and cross
      reactivity identified between G10 and G3 rotaviruses.

PMID- 15494267
TI  - Isotype immune response of IgG antibodies at the persistence and reactivation
      stages of human herpes virus 6 infection.
AB  - BACKGROUND: Infections with human herpes virus 6 (HHV-6) are very common. After
      primary infection, the virus remains latent and persists at low level in cells
      and tissues. Not usually associated with disease in the immunocompetent host, HHV
      6 infection is a major cause of opportunistic viral infections in the
      immunosuppressed. The different stages of HHV-6 infection are difficult to
      characterize in the laboratory. OBJECTIVES: The aim of this paper was to assess
      the isotype patterns of IgG antibodies against HHV-6 in seropositive subjects
      during different stages of the virus activity. STUDY DESIGN: From a total of 190
      human serum samples from 43 healthy children, 24 pregnant women and 24 patients
      with bone marrow transplants, 111 sera were processed by indirect
      immunofluorescence assay for the detection of IgG1, IgG2, IgG3 and IgG4 specific
      antibodies. The mean geometrical title (MGT) of the antibodies was calculated.
      RESULTS: All pregnant women had IgG1 (24/24; 100%; MGT 46). A 95% (41/43) of
      healthy infants had IgG1 (MGT 57). In bone marrow transplants, 58% (14/24) of the
      patients showed seroconversion (MGT 529) with an isotype response of IgG1 and
      IgG4 during the observation period. Remaining bone marrow transplant patients,
      who had the IgG without any variations (MGT 184), had isotype IgG1. CONCLUSIONS:
      These results revealed two different immune isotype response patterns. One of
      them is restrictive to IgG1 in the latent phase of HHV-6 infection in healthy
      children, pregnant women and transplant patients with stable levels of antibodies
      whereas IgG1 and IgG4 are detected in the reactivation of HHV-6 in transplant
      patients. The IgG isotype immune responses may contribute to the existing set of
      serological markers in characterizing the different stages of natural infection
      of HHV-6.

PMID- 15494268
TI  - Factors associated with HPV persistence after treatment for high-grade cervical
      intra-epithelial neoplasia with large loop excision of the transformation zone
      (LLETZ).
AB  - BACKGROUND AND OBJECTIVE: Human Papillomavirus (HPV) persistence after high-grade
      cervical intra-epithelial neoplasia (CIN) removal may be associated with residual
      lesions or risk of disease recurrence. Knowledge regarding the factors associated
      with HPV persistence following CIN treatment is still limited. The main purpose
      of this longitudinal study was to assess the association between characteristics
      of the patients and their cervical lesions with high-risk HPV-type persistence,
      detected by commercially available Hybrid Capture II (HC II), after CIN 2 and 3
      treatment with large loop excision of the transformation zone (LLETZ). STUDY
      DESIGN: For this cohort study, a total of 94 women submitted to LLETZ between
      March 2001 and September 2002 were included. Only women with at least one follow
      up visit at 6 or 12 months and confirmed CIN 2 or 3 in the cone specimen were
      considered. In each visit women answered to a questionnaire and undertook Pap
      smear and HC II specimens collection. McNemar's, chi-square and Fisher tests were
      used for univariate analysis. Generalized Estimating Equations (GEE) were used
      for multivariate analysis. All calculations were performed within 95% confidence
      intervals (95% CI). RESULTS: Histological evaluation showed 12 (13%) women with
      CIN, 2 and 82 (87%) with CIN 3 and conization margins were compromised in 27
      (29%) cases. Eighty-seven (92%) women showed positive HC II tests prior to LLETZ.
      Of women initially HPV negative, none had a positive HC II during follow-up. The
      proportion of positive HPV tests was reduced from 92% to 20%(P < 0.01) at the
      first visit and to 22% (P < 0.01) at the second visit after LLETZ. Multivariate
      analysis showed that smoking and age above 35 years (irrespective of margin
      status) were strongly associated with positive HPV during follow-up. CONCLUSION:
      HPV persistence following LLETZ was associated with smoking and with the
      interaction between age and conization margins.

PMID- 15494269
TI  - Quantitation of HTLV-I and II proviral load using real-time quantitative PCR with
      SYBR Green chemistry.
AB  - BACKGROUND: Human T-lymphotropic virus type I (HTLV-I) is linked etiologically
      with adult T cell leukemia/lymphoma and HTLV-I-associated myelopathy/tropical
      spastic paraparsis (HAM/TSP). Human T-lymphotropic virus type II (HTLV-II) is
      associated with HAM/TSP and, in HIV coinfected patients only, rare cases of
      cutaneous T cell lymphoma. Proviral load may be important in the pathogenesis of
      HTLV-associated disease. MATERIALS AND METHODS: A real time quantitative PCR
      assay using SYBR Green intercalation was established. Primers targeting the tax
      region were standardized against MT2 and MOT cell line DNA for HTLV-I and HTLV
      II, respectively. HTLV-I/II copy number was normalized to the amount of cellular
      DNA by quantitation of the HLA-DQ alpha gene. We measured proviral load in
      peripheral blood mononuclear cells (PBMCs) in a large cohort of 120 HTLV-I and
      335 HTLV-II seropositive former blood donors. We also assessed the intra- and
      inter-assay reproducibility of the assay. RESULTS: Proviral load for HTLV-I
      infected patients ranged from 3.1 x 10(0) to 1.8 x 10(5)copies/10(6) PBMCs with a
      mean of 1.6 x 10(4) and a median of 3.0 x 10(3). HTLV-I was undetectable in 7 of
      120 cases (5.8%). Proviral load for HTLV-II infected patients ranged from 1.1 x
      10(0) to 1.0 x 10(6)copies/10(6) PBMCs with a mean of 2.8 x 10(4) and a median of
      5.0 x 10(2). HTLV-II was undetectable in 31 out of 335 cases (9.3%). CONCLUSION:
      The assay has excellent dynamic range from 10(6) to 10(0)copies/reaction, good
      intra- and inter-assay reproducibility, and a lower limit of detection of a
      single copy per reaction. The sensitivity and high dynamic range allow
      determination of a broad range of HTLV-I/II proviral load in clinical subjects.
      This assay will facilitate the study of the relationship between proviral load
      and pathogenesis.

PMID- 15494270
TI  - New variant of the human metapneumovirus (HMPV) associated with an acute and
      severe exacerbation of asthma bronchiale.
AB  - Recently, an increasing number of studies demonstrated that the human
      metapneumovirus (HMPV) causes mild to severe respiratory infections in children
      and immunosuppressed adults, and may be a frequent but somewhat undervalued
      pathogen. Here, we report the detection of a new variant of HMPV that is not
      closely related to the HMPV strains described until now. The strain was detected
      in a 6.5-year-old girl with an acute and severe exacerbation of asthma bronchiale
      triggered by an infection with a newly detected HMPV variant. The presented data
      provide new information on genetic heterogeneity of HMPV and necessitate an
      optimization of diagnostic procedures for the detection of HMPV infection.

PMID- 15494271
TI  - Persistence of West Nile Virus (WNV) IgM antibodies in cerebrospinal fluid from
      patients with CNS disease.
AB  - The Michigan Department of Community Health (MDCH) reported 644 laboratory
      positive human cases of West Nile Virus (WNV) in the 2002 outbreak in the US, of
      which 559 cases presented with either meningitis or encephalitis. The first line
      test utilized for diagnosis of WNV infection was the immunoglobulin M (IgM)
      capture enzyme-linked immunosorbent assay (MAC-ELISA). We continued testing for
      WNV even during winter months of the year 2002-2003 due to the awareness of other
      modes of WNV transmission (blood transfusion, organ transplantation,
      transplacental, breast milk, and occupational) as well as concern for people
      traveling to endemic areas. As a result of year-round testing for WNV infections
      during 2002-2003, we detected WNV IgM-specific antibodies in cerebrospinal fluid
      (CSF) specimens from three patients persisting for 110, 141, and 199 days post
      acute phase infection in patients with central nervous system (CNS) disease. This
      is a new observation and there is no published data on the persistence of WNV IgM
      antibodies in CSF specimens beyond 47 days. Thus, it is important to note that
      the presence of WNV IgM class antibodies may not always reflect acute phase
      infection with this virus.

PMID- 15494272
TI  - Detection of human papillomavirus DNA in breast cancer of patients with cervical
      cancer history.
AB  - BACKGROUND: Recent studies have revealed a possible role for the human
      papillomavirus (HPV) in the pathogenesis of breast cancer. In this study,
      patients having both a history of invasive cervical cancer and breast cancer as
      second primary cancer were selected for enrolment in a study of breast carcinomas
      for the presence of HPV. METHODS: Paraffin-embedded tissue from cervical cancer,
      pelvic lymph nodes, breast cancer and axillary lymph nodes of eleven patients
      were examined for the presence of HPV DNA using a polymerase chain reaction -
      enzyme immuno assay. DNA extraction was performed with the "QIAamp Tissue Kit"
      according to the manufacturer's instructions. Additionally, serum samples taken
      between diagnosis of cervical and breast cancer, were analyzed for the presence
      of HPV DNA to examine a possible haematogenous spread of oncogenic HPV DNA.
      RESULTS: All cervical carcinomas were HPV-positive. HPV DNA was detected in seven
      out of eleven cases in breast cancer and/or axillary lymph node tissue. Six
      patients had the same HPV type (HPV-16) in cervical cancer and in the
      corresponding breast cancer/lymph node tissue. In one case, the same HPV DNA type
      (HPV 16) was detected in cervical cancer, breast cancer and serum sample.
      CONCLUSION: These results suggest that HPV DNA might be transported from the
      original site of infection to the breast tissue by the bloodstream, and that it
      is possibly involved in the carcinogenesis of breast neoplasia in some patients.

PMID- 15494273
TI  - Effects of long-term lamivudine therapy in renal-transplant patients.
AB  - BACKGROUND: Following renal transplantation (RT), chronic immunosuppression is
      associated in hepatitis B virus (HBV) (+) patients with a flare-up of the
      disease, which might be harmful in the long term. OBJECTIVES: We report on the
      effect of long-term lamivudine therapy given at an initial daily dose of 100mg in
      18 HBV (+) RT patients. RESULTS: When lamivudine therapy was commenced, 14
      patients (77%) had an increase in their aspartate (AST) and alanine (ALT)
      aminotransferase levels. During a mean follow-up, under treatment, of 36.5 +/-
      3.5 months (up to 66 months), 10 patients (55%) had a sustained partial (HBV DNA
      < 4 x 10(5)copies/ml) (n = 4) or complete (HBV DNA < 400 copies/ml) (n = 6)
      virological response. Overall, 12 virological breakthroughs were observed. Of
      those who were HBe Ag(+) prior to lamivudine therapy (n = 4), one seroconverted
      to HBe Ab during therapy. At the last follow-up, AST and ALT levels were normal
      in 13 patients. When liver biopsy was repeated during treatment (n = 15), the
      virological responders showed a significant decrease in total Knodell score from
      10 +/- 0.6 to 7 +/- 1 (P = 0.04), but no significant change in the stage of
      fibrosis. Conversely, in those patients with high HBV DNA titers, there were no
      significant changes in the total Knodell score or in the grade of fibrosis.
      CONCLUSION: In conclusion, lamivudine therapy is safe in HBV(+)ve renal
      transplant patients. However, even if the full and partial virological response
      rates are still high (55%) in the long term, relapse or primary non-responses
      occur. The implementation of alternative efficient strategies is warranted.

PMID- 15494275
TI  - Significance of qualitative PCR detection method for pre-emptive therapy of
      cytomegalovirus infection in patients after allogeneic hematopoietic stem cell
      transplantation--single-centre experience.

PMID- 15494274
TI  - Effects of early corticosteroid treatment on plasma SARS-associated Coronavirus
      RNA concentrations in adult patients.
AB  - BACKGROUND: The effect of corticosteroid treatment on the viral load of Severe
      Acute Respiratory Syndrome (SARS) patients is unknown. OBJECTIVE: To compare the
      plasma SARS-CoV RNA concentrations in ribavirin-treated patients who received
      early hydrocortisone therapy with those who received placebo. STUDY DESIGN:
      Serial plasma SARS-CoV RNA concentrations measured in the setting of a
      prospective, randomized double-blinded, placebo-controlled trial designed to
      assess the efficacy of "early" (<7 days of illness) hydrocortisone use in
      previously healthy SARS patients were analyzed. SARS-CoV RNA was quantified using
      a one-step real-time RT-PCR assay targeting the nucleocapsid gene. RESULTS: Among
      16 non-ICU cases, SARS-CoV RNA was detected in plasma since day 3-4 after fever
      onset; viral concentration peaked in the first week, which then rapidly declined
      in the second week of illness. On days 8, 12, 16, and 20, the cumulative
      proportion of patients with undetectable virus in plasma was 31%, 69%, 92%, and
      100%, respectively. Plasma SARS-CoV RNA concentrations in the second and third
      week of illness were significantly higher in patients who received initial
      hydrocortisone treatment (n = 9), as compared to those who received placebo (n =
      7)(AUC; Mann-Whitney, P = 0.023). The median time for SARS-CoV to become
      undetectable in plasma was 12 days (11-20 days) versus 8 days (8-15 days),
      respectively. CONCLUSION: Our findings suggested "early" corticosteroid treatment
      was associated with a higher subsequent plasma viral load.

PMID- 15494276
TI  - Comparison of hepatitis C virus RNA detection in plasma, whole blood and
      peripheral blood mononuclear cells of patients with occult hepatitis C virus
      infection.

PMID- 15494277
TI  - Virological response in post-partum treated chronic hepatitis C women with
      pegylated interferon-alpha plus ribavirin. A case-control study.

PMID- 15494279
TI  - The role of endoscopy in early postoperative haemorrhage.
AB  - Diagnostic as well as therapeutic endoscopy has a decisive role in management of
      early postoperative haemorrhage. Endoscopy combines easy access to the upper and
      lower gastrointestinal tract and application of an array of interventional tools.
      In near future, even the small bowel will be accessible for diagnostic and
      therapeutic measures due to the advent of double-balloon enteroscopy. Thus, the
      endoscopist increasingly replaces the surgeon for diagnosis and therapy of
      postsurgical bleeding. Published data on frequency and aetiology of postoperative
      haemorrhage are scarce and mainly casuistic. Sources of gastrointestinal bleeding
      associated with surgery may be: anastomotic ulcers, mucosal ischaemia, 'stress'
      ulcers, reflux-induced lesions, coagulopathies (e.g. in sepsis or after organ
      transplantation) and aortoenteric fistula after bypass surgery. The endoscopist
      will frequently identify the culprit lesion and guide further management of the
      patient (e.g. endoscopic approach, repeated surgery, interventional radiology).
      All accessible lesions in postoperative haemorrhage should primarily be treated
      by endoscopic means, except aortoenteric fistulas. There is even a place for
      repeated endoscopy in recurrent bleeding. In the face of lacking controlled data,
      the endoscopist often has to rely on his personal experience in the selection of
      therapeutic options.

PMID- 15494280
TI  - Endoscopic and surgical management of leakage and mediastinitis after esophageal
      surgery.
AB  - Due to the specialisation of esophageal surgery a significant reduction of post
      surgical mortality was possible during the last few decades. Nevertheless a high
      complication rate of about 30% remains even in the hands of experienced surgeons.
      Anastomotic leakage has an incidence between 5 and 30% leading to serious
      postoperative morbidity. With a broad range of conservative and endoscopic
      therapeutic methods there is encouraging progress in shortening the time to
      closure of the leakage and reducing the risk of severe systemic complications
      such as sepsis or malnutrition. If conservative therapy fails, re-surgery remains
      as an ultima-ratio option.

PMID- 15494281
TI  - Endoscopic and surgical management of bile duct injury after laparoscopic
      cholecystectomy.
AB  - Laparoscopic cholecystectomy has become the first choice of management for
      symptomatic cholecystolithiasis. While it is associated with decreased
      postoperative morbidity and mortality, bile duct injuries are reported to be more
      severe and more common (0-2.7%), when compared to open cholecystectomy (0.2-0.5%)
      [New Engl. J. Med. 234 (1991) 1073; Am. J. Surg. 165 (1993) 9; Surg. Clin. N Am.
      80 (2000) 1127]. These bile duct injuries include leaks, strictures, transection
      and removal of (part of) the duct, with or without vascular damage. Bile duct
      injury might be due to misidentification of the biliary tract anatomy due to
      acute cholecystitis, large impacted stones, short cystic duct, anatomical
      variations, but also due to technical errors leading to bleeding with subsequent
      clipping and coagulation trauma [Ann. Surg. 237 (2003) 460]. Early recognition
      and adequate multidisciplinary approach is the cornerstone for the optimal final
      outcome. Suboptimal management of injuries often leads to more extensive damage
      to the biliary tree and its vasculature with as consequences biliary peritonitis,
      sepsis, abscesses, multiple organ failure, a more difficult (proximal)
      reconstruction and in the long run, secondary biliary cirrhosis, and liver
      failure. Despite increasing experience in performing laparoscopic
      cholecystectomy, the frequency of bile duct injuries has not decreased [Ann.
      Surg. 234 (2001) 549]. Therapy encompasses endoscopic stenting, percutaneous
      transhepatic dilatation (PTCD) and surgical reconstruction.

PMID- 15494282
TI  - Management of bleeding and leakage after pancreatic surgery.
AB  - Pancreatic surgery has advanced considerably during the past decades. Recent
      studies report reduced morbidity rates and virtually no mortality after
      resection. However, postoperative complications are still a formidable menace. In
      this chapter we discuss the management of postoperative bleeding and leakages
      which are considered the most feared complications, and discuss the advent of
      minimal invasive methods for management of these complications. Patients who
      develop postoperative bleeding almost always present with septic complications
      and a sentinel bleed before onset of bleeding. These patients should undergo
      early diagnostic angiography followed by embolisation. If this does control the
      bleeding an emergency laparotomy should be performed as last resort. Patients who
      develop pancreatic leakage are generally managed conservatively by means of
      percutaneous drainage. Aggressive surgery should be performed at the first sign
      of severe sepsis. The condition of the pancreatic remant found during reoperation
      dictates the type of surgical intervention best performed.

PMID- 15494283
TI  - Postoperative leakage and abscess formation after colorectal surgery.
AB  - Anastomotic leaks following colorectal surgery may be divided into those which
      are clinically significant and those which are not. Leakage occurs in 3.4-6% of
      all colorectal cases. It is most commonly associated with rectal anastomoses,
      being clinically significant in 2.9-15.3% of cases. Mortality following a leak
      may be 6.0-39.3%. There is no evidence that preoperative bowel preparation
      reduces the rate and consequences of leaks. There is no evidence for the use of
      drains when an anastomosis has been made outside the pelvis, but pelvic drainage
      may be important after anterior resection. The use of covering stomas has not
      been shown to reduce leak rate but does mitigate the clinical effects of leaks.
      Prompt diagnosis and further laparotomy can reduce mortality following leakage.
      Intra-abdominal abscesses can in most cases be treated by radiologically guided
      drainage. Anastomotic leaks are the most common cause of anastomotic strictures
      and are also associated with increased rates of local recurrence of cancer.

PMID- 15494284
TI  - Early postoperative complications following liver transplantation.
AB  - Liver transplantation is a highly successful treatment for patients with end
      stage liver disease and acute liver failure. However, serious postoperative
      complications can significantly compromise patient survival. Complications can be
      technical, medical, or immunological in nature. The risk of developing early
      postoperative complications is associated with the patient's preoperative
      condition, the quality of the donor liver, the quality of the donor and recipient
      procedure, initial graft function, and perioperative anaesthesiological and
      intensive care management. The patient's preoperative condition can include
      gastrointestinal bleeding, acute renal failure, a requirement for cathecholamines
      or mechanical ventilation, and prolonged encephalopathy for the most detrimental
      risk factors for developing early postoperative complications. The necessity for
      prolonged mechanical ventilation or the requirement for reintubation after
      transplantation can significantly increase the risk of developing pneumonia,
      sepsis, and multiple organ dysfunction. A decrease in infectious and other
      complications can be achieved by early postoperative enteral nutition, including
      the application of probiotics.

PMID- 15494285
TI  - Chronic symptoms after subtotal or partial oesophagectomy: diagnosis and
      treatment.
AB  - In the great majority of patients, subtotal or partial oesophagectomy is
      performed because of malignancy, for which wide local excision and additional
      lymphadenectomy are indicated. Except in patients with early lesions, the vagal
      nerves have to be sacrificed bilaterally, which can induce a great variety of
      functional abnormalities. The continuity of the gastrointestinal tract is
      preferably restored by using a whole-stomach interposition or gastric tube. The
      oesophago-gastric anastomosis is critically vascularized and carries a
      significant risk of benign fibrotic stricturing, especially when it is located in
      the neck. Acid or biliary reflux may result in persistent oesophagitis and the
      development of Barrett's metaplasia in the remnant oesophagus. The reservoir
      capacity of the gastric tube is limited, whereas the emptying rate can vary
      considerably, leading to complaints of either gastric retention or intestinal
      dumping. It is not clear whether or not gastric drainage procedures are
      beneficial. Recurrent nerve damage with vocal cord paralysis may result in
      aspiration and recurrent pulmonary infection. The permanent threat of recurrent
      disease combined with the substantial physical impact of an extensive surgical
      procedure inducing a wide range of functional disturbances of the
      gastrointestinal tract has a great influence on quality of life, at least
      temporarily. The late complications of anastomotic stricturing and the functional
      consequences of bilateral vagotomy, gastric tubulization and gastric pull-up will
      be reviewed. Moreover, the general and specific changes in quality of life will
      be addressed.

PMID- 15494286
TI  - Postgastrectomy syndromes--diagnosis and treatment.
AB  - The stomach has a variety of functions that are lost with gastrectomy. Since
      nowadays a significant number of patients are long-term survivors, consequences
      of this loss need to be considered by gastroenterologists and surgeons alike.
      Abnormal transit, disturbed general nutrition and micronutrient deficiencies are
      the most common problems. The main resulting symptoms are early and late dumping,
      reflux esophagitis, weight loss, anemia, and osteopathy. It is not definitively
      clear if pouch reconstruction can really improve the situation. Dietary measures,
      rarely re-operation, and in particular adequate follow-up of metabolic and
      nutrition parameters with consequent substitution are the main therapeutic
      necessities.

PMID- 15494287
TI  - Complications after anti-reflux surgery.
AB  - Anti-reflux operations are frequently performed in a variety of different
      hospital categories. Surgical repair of the reflux-preventing mechanisms is very
      effective in preventing a relapse of the reflux, but the side effects of surgery
      sometimes mar an otherwise excellent postsurgical result. The side effects of
      anti-reflux surgery are mainly due to an overcorrection of the anti-reflux
      mechanisms in the gastro-oesophageal junction area. A restrained passage of
      swallowed food through the gastro-oesophageal junction is a fairly regular
      phenomenon postoperatively, although it causes astonishingly few symptoms except
      during the early postoperative period. No patient should be able to vomit after a
      well-functioning anti-reflux procedure, although the ability to belch is usually
      reported to be maintained despite objective evidence to suggest significant
      deficiencies, which may cause bloating and rectal flatulence. A variety of
      factors have been suggested to counteract some of the side effects of anti-reflux
      surgery. The best-documented preventive strategy presented so far is to carry out
      a posterior partial fundoplication and to ensure that the patient is operated on
      in a high-volume, specialised centre.

PMID- 15494288
TI  - Exocrine and endocrine pancreatic insufficiency after pancreatic surgery.
AB  - The pancreas is the central organ for digestion and for control of glucose
      homeostasis. Indications for major pancreatic surgery are complications of
      chronic and acute pancreatitis and pancreatic malignancies. The postoperative
      pancreatic function is determined by type of resection, resection of adjacent
      organs, the underlying disease and preoperative pancreatic function. Standard
      treatment following major pancreatic surgery includes the administration of
      pancreatic enzyme preparations and inhibition of acid secretion by proton pump
      inhibitors. Postoperatively most patients also develop diabetes mellitus, which
      requires insulin substitution. Hypoglycemia is the most difficult clinical
      problem to handle following total pancreatectomy.

PMID- 15494289
TI  - Endoscopic management of pancreatic fistula after pancreatic and other abdominal
      surgery.
AB  - Post-operative pancreatic fistulae represent a challenge for all the actors in
      gastroenterology: for surgeons, because they want to prevent and treat
      conservatively this complication since re-operation is associated with high
      morbidity and mortality rates; for radiologists, because they have to provide the
      best staging and informations without any additional risk; and for endoscopists,
      because endoluminal treatment is emerging as a safe and effective procedure
      provided it is performed in highly experienced tertiary centres in the setting of
      a multidisciplinary approach. Herein, we review the definitions, the causes, the
      staging and the possible options to prevent or treat post-operative pancreatic
      fistulae. Special attention is paid to the endoscopic management of this
      complication: including the relief of ductal obstructions, the stenting of
      leakages and the drainage of bulging or non-bulging fluid collections. Practical
      problems and issues are clearly outlined as well as the need for future
      improvements in staging and management of the patients having such complications.

PMID- 15494290
TI  - Management of the short bowel syndrome after extensive small bowel resection.
AB  - Short bowel syndrome (SBS) is a global malabsorption syndrome that results from
      extensive intestinal resections. It used to be a typical complication of
      repetitive bowel resections in patients with Crohn's disease. However, due to
      improved medical and surgical therapies for these patients it currently occurs
      more frequently as a consequence of vascular disorders in adults (intestinal
      infarction) and congenital aberrations in children, respectively. Adequate
      therapy depends on the degree of (small) bowel losses and on resulting functional
      disturbances. Moreover, it must be adjusted to the postoperative adaptation
      process, which consists of three phases: The immediate acute phase lasts less
      than 4 weeks and serves to stabilise the patient. The subsequent year should be
      used to induce maximal adaptation by gradually increasing nutrient exposure. When
      maximal stimulation of nutrient absorption has been achieved, permanent
      maintenance nutrition treatment should be defined individually, dependent on
      extent and quality of nutritive deficits. In patients with Crohn's disease,
      optimal treatment of the underlying disease is of pivotal importance in order to
      avoid a further reduction of absorptive capacity or other complications. Current
      investigations aim at improving the adaptation process by administration of
      specific diets and growth hormones. With these, it appears possible to treat even
      some patients with very short bowel, i.e. less than 50 cm of small intestine
      left, with oral nutrition, only. Still, a considerable proportion of patients
      will need long-term parenteral nutrition. If young patients experience
      intolerable complications of parenteral nutrition, intestinal transplantation may
      be considered as a high risk therapy of last choice.

PMID- 15494291
TI  - Management of pouch dysfunction or pouchitis with an ileoanal pouch.
AB  - Pouchitis, a non-specific inflammation of the ileal reservoir, is the most
      frequent long-term complication after pouch surgery for ulcerative colitis.
      Incidence rates vary widely. The etiology is still unknown, but genetic
      susceptibility and fecal stasis with bacterial overgrowth seem to be important
      factors. A clinical diagnosis should be always confirmed by endoscopy and
      histology, and Pouchitis Disease Activity Index (PDAI), based on clinical
      symptoms, endoscopic appearance and histologic findings, represents an objective
      and reproducible scoring system for pouchitis. The treatment of pouchitis is
      largely empiric given the few controlled studies available. Antibiotics,
      especially metronidazole and ciprofloxacin, are the therapy of choice. Chronic
      pouchitis occurs in about 10-15% of patients; in these cases, further diagnostic
      tests should be performed to exclude alternative diagnoses. Highly concentrated
      probiotics (VSL#3) have been shown to be effective in preventing the onset and
      relapse of pouchitis.

PMID- 15494292
TI  - State of the science for myelodysplastic syndrome: prognosis and promise of new
      therapies.

PMID- 15494293
TI  - Pathobiology, classification, and diagnosis of myelodysplastic syndrome.
AB  - Recent advances in molecular genetics have advanced the knowledge regarding the
      mechanisms leading to myelodysplastic syndrome (MDS), secondary acute myeloid
      leukemia, and therapy-induced MDS. Unfavorable cytogenetics associated with this
      group of disorders includes monosomy or deletion of the long arm of chromosomes 5
      or 7, inversions of chromosome 3, translocations, deletions, and trisomies
      involving several other chromosomes. These unbalanced chromosomal aberrations
      result in hemizygosity and unmasking of oncogenes, changes in levels of expressed
      genes, or inactivation of tumor suppressor genes. It is evident that the
      cytogenetics associated with MDS is highly complex and heterogeneous, leading to
      an equally heterogeneous manifestation of the disease. Classifications, initially
      defined by the French-British-American group followed by the World Health
      Organization, and now by the International Prognostic Scoring System, have
      determined prognosis and helped develop treatment strategies for these patients,
      thus reducing their potential to develop acute leukemia. To date there are seven
      different prognostic schemas. These are constantly being improved so that MDS
      patients, who tend to be elderly, can be suitably treated. Additionally,
      treatment considerations and prognosis are different for patients who develop
      therapy-related MDS or for the juvenile population than for those with de novo
      MDS. The genetic alterations in MDS bone marrow and blood cells have been
      identified and possible models have been proposed for the development and
      progress of MDS, from the early stage to late-stage MDS evolving to acute myeloid
      leukaemia. As the functional mechanisms behind these chromosomal changes are
      being revealed, new therapies based on these mechanisms are currently being made
      and tested.

PMID- 15494294
TI  - Transplant strategies for myelodysplastic syndrome.
AB  - Myelodysplastic syndrome (MDS) is an acquired bone marrow disorder characterized
      by ineffective hematopoiesis and cellular dysfunction and has an increased risk
      of transforming into acute myeloid leukemia. Most patients are of advanced age
      with attendant comorbidities, making treatment difficult. Current treatment
      options have included supportive care and, in difficult cases, chemotherapy
      regimens designed for acute leukemia patients. A major effort has been made to
      determine the role of stem cell transplantation in adult MDS patients, currently
      the only curative option available for them. Based on relapse rates, studies
      indicate that allogeneic and autologous transplants provide better antileukemic
      activity than intensive chemotherapy schedules. Use of DNA methyltransferase
      inhibitors may assist in managing MDS patients while awaiting a transplant match,
      but the procedural mortality for transplant remains high. Reduced conditioning or
      nonmyeloablative conditioning, particularly in the elderly, has been attempted
      with some success. Reduced conditioning also increases the graft-versus-leukemia
      effect, allowing for a higher percentage of disease-free survival. Current use of
      peripheral blood as a source of stem cells for autotransplant is associated with
      an extremely low procedural mortality. Improvement in such transplant procedures
      as myeloablation, preparation of the autograft, and posttransplant prophylaxis
      are improving recovery rates for these patients. In addition, as the biology of
      this disease is being revealed, newer options will become available in the near
      future.

PMID- 15494295
TI  - Nucleoside analogs and antimetabolite therapies for myelodysplastic syndrome.
AB  - Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic
      disorders. Therapeutic interventions for MDS other than allogeneic bone marrow
      transplantation have been palliative. Because most of the patients are elderly
      and may not be candidates for ablative transplant conditioning regimens,
      treatment has focused on supportive care. Recently, several novel biological and
      chemotherapeutic agents have demonstrated activity in MDS and are being
      incorporated into the treatment paradigm. These agents are based on specific
      mechanisms aimed at angiogenesis in the bone marrow, secretion of growth factors
      and/or their receptors, and modulators in their intracellular pathways. Several
      agents are in the initial stages of clinical trial, including anti-vascular
      endothelial growth factor, bevacizumab, receptor tyrosine kinase inhibitors,
      farnesyl transferase inhibitors, protein kinase C inhibitors, matrix
      metalloproteinase inhibitors and other agents such as thalidomide and arsenic
      trioxide. Novel chemotherapeutic agents include topoisomerase inhibitors such as
      topotecan and rubitecan, and deoxyadenosine analogues such as troxacitabine,
      tezacitabine, and clofarabine. Prognostic factors predicting response in MDS
      patients treated with intensive chemotherapy have been identified and include
      younger age and favorable cytogenetics.

PMID- 15494296
TI  - DNA methyltransferase inhibitors in myelodysplastic syndrome.
AB  - Myelodysplastic syndrome (MDS) resulting from a clonal stem cell is a
      heterogeneous disease that complicates therapeutic decisions. Most patients are
      of advanced age with attendant comorbities, making treatment choices difficult.
      Current treatment options include bone marrow transplant, which appears to be the
      only curative option, and supportive care. In elderly patients, risks for
      transplant are high and supportive-care treatments are ineffective. However,
      considerable progress has been made in understanding the pathology of MDS, which
      results from a series of progressive chromosomal assaults that lead to a release
      of various cytokines, loss of tumor suppressor genes, and changes in signal
      transduction pathways and in immune pathways. The neoplastic clone does not
      appear to mature; it stays in a fixed state of differentiation beyond which these
      cells do not progress. Hypermethylation of specific DNA sequences, which results
      in silencing transcription of proteins involved, has been implicated in this lack
      of differentiation. New clinical discoveries include the potential to block
      methylation, release transcriptional inactivation, and stimulate the normal
      myeloid cells to resume growth and differentiation. Therapies aimed at these new
      findings hold promise for safer treatment protocols and improved outcomes. One of
      these agents, azacitidine, is a nucleoside analog that has shown promising
      efficacy in high-risk MDS patients. Phase III studies have shown significant
      improvement in survival and quality of life with minimal side effects. Prolonged
      administration of azacitidine results in reactivation of normal hematopoiesis by
      its effect on inhibiting DNA methylation.

PMID- 15494297
TI  - Histone deacetylase inhibitors in myelodysplastic syndrome.
AB  - Histone deacetylase (HDAC) inhibitors are amongst the newer therapies being
      introduced in refractory, relapsed, and resistant disease. These agents are
      mechanism-based and their use is targeted to the diseased cell or tissue. HDACs
      are key enzymes in the regulation of gene expression. They maintain a dynamic
      equilibrium in the acetylation state of highly conserved lysine residues on
      histones by which they regulate chromatin remodeling and gene expression. Changes
      in growth and differentiation leading to malignancy appear to occur by
      alterations in transcriptional control and gene silencing. Histone acetylation
      and DNA methylation have been implicated in these aberrant phenotypes. Inhibitors
      of DNA methylation such as 5-azacytidine or 5-azadeoxycytidine have been able to
      reverse DNA methylation patterns and have shown promise in patient studies.
      Similarly, HDAC inhibitors block deacetylation function, causing cell cycle
      arrest, differentiation, and/or apoptosis of many tumors. Several HDAC inhibitors
      have exhibited potent antitumor activity in human xenograft models, suggesting
      their usefulness as novel cancer therapeutic agents. Several are currently in
      phase I/II clinical trials both in hematological malignancies and in solid
      tumors. Agents used initially, such as phenylbutyrate, are effective in
      millimolar concentrations. Newer agents are being developed and these are
      effective at much lower concentrations and are relatively less toxic. In
      particular, hydroxamic acid-based polar compounds and cyclic tetrapeptides have
      shown activity against cancers at well-tolerated doses.

PMID- 15494298
TI  - Inhibitors of signaling in myelodysplastic syndrome.
AB  - Treatment of myelodysplastic syndrome (MDS) has been hampered by the lack of
      understanding of the molecular and biological abnormalities associated with this
      disease. Biological abnormalities may lead to typical phenotypic changes in more
      differentiated cells. Recent developments in the natural history and underlying
      molecular mechanisms of MDS and acute myeloid leukemia (AML) have identified new
      molecular therapeutic targets. Several new classes of drugs have shown promise in
      early clinical trials and may alter the standard of care of these patients. Among
      these new drugs are farnesyltransferase inhibitors, receptor tyrosine kinase
      inhibitors, protein kinase C inhibitors, and VEGF inhibitors. These agents have
      been tested in patients with solid tumors and hematological malignancies such as
      AML and MDS. Most of the studies in MDS are in early stages of development, where
      doses are being determined based on the experience in refractory or relapsed AML
      or solid tumors. Future therapies in MDS will attempt to resolve cytopenias,
      eliminate malignant clones and allow differentiation by attacking specific
      mechanisms of the disease.

PMID- 15494299
TI  - Modulation of angiogenesis in patients with myelodysplastic syndrome.
AB  - Current investigations have revealed that angiogenesis plays a role in the
      pathogenesis of high-risk myelodysplastic syndrome (MDS) and acute myeloid
      leukemia, and in the mechanisms of disease progression. Secretion of cytokines
      and growth factors modulates angiogenesis in the marrow leading to increased
      vascularity and sustenance of the clonal population. For high-risk MDS patients
      older than 60 years who are not eligible for aggressive chemotherapy or stem cell
      transplant, there are few therapeutic options other than supportive treatment.
      Recent delineation of the pathobiology of MDS has resulted in the development of
      new agents and treatment modalities that impact on these mechanisms. One of the
      features of bone marrow pathology is the presence of new vessels, which appear to
      sustain growth and the hypercellularity of the marrow. Blocking angiogenesis may
      reduce the microvessel density of the marrow, cellularity, and disease
      progression. Angiogenesis can be targeted by inhibition of vascular endothelial
      growth factor (VEGF), which modulates new vessel growth, by the use of antibodies
      aimed at VEGF and its receptors, as well as receptor tyrosine kinases that block
      VEGF signaling. Other agents include inhibitors of farnesyl transferase and
      protein kinase C, which affect upstream modulators of growth factors and their
      receptor interactions; matrix metalloproteinases, which disrupt matrices and
      adhesion function promoting vessel growth; and other inhibitors with broader
      function, such as endostatin, thalidomide, and related analogues.

PMID- 15494300
TI  - Modulation of drug resistance transporters as a strategy for treating
      myelodysplastic syndrome.
AB  - Resistance to chemotherapy is an obstacle to the successful treatment of acute
      myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The failure of
      therapeutic treatment may be due to the development of multidrug resistance
      (MDR), mechanisms of which include upregulation of membrane-resident transporters
      which efflux chemotherapeutic drugs from tumor cells, and failure of the cancer
      cell to undergo apoptosis in response to chemotherapy. Membrane transporter-based
      drug efflux transporters have been extensively studied, and agents that block
      drug efflux have been found and investigated. Presence of P-glycoprotein (Pgp,
      MDR1, ABCB1), a member of the ATP-binding cassette (ABC) transporter family, has
      been reported to correlate with poor prognosis in AML and MDS. In MDS, Pgp
      expression increases as the disease progresses. Overexpression of other
      transporters, such as the multidrug resistance protein (MRP1, ABCC1), and the
      vault-associated transporter lung resistance protein have been shown as well in
      both MDS and AML, but their prognostic relevance is not clear. Recently, a novel
      ABC half-transporter, the breast cancer resistance protein (ABCG2) has been found
      in approximately 30% of AML cases, and may play a role in resistance to
      chemotherapy. In clinical trials in MDS, first-generation Pgp blockers, such as
      cyclosporin-A and verapamil, were minimally effective, non-specific, and toxic.
      However, another first-generation blocker, quinine, was used in MDS and may
      specifically benefit MDS patients overexpressing Pgp. A second-generation drug,
      the non-immunosuppressive cyclosporine analog valspodar (PSC833), was studied in
      AML and MDS, and was highly toxic, resulting in the need to reduce the dosage of
      the chemotherapeutic drugs as a result of valspodar reducing the clearance of the
      chemotherapeutic agents. Third-generation drugs, which are highly specific for
      Pgp and which seem to have only modest effects on drug clearance, include
      tariquidar, zosuquidar, laniquidar, and ONT-093. These are all in phase I/II
      trials and show promise for future treatment.

PMID- 15494301
TI  - Immunobiologic therapies for myelodysplastic syndrome.
AB  - Recent progress in understanding the pathobiology of the myelodysplastic syndrome
      (MDS) and acute myeloid leukemia (AML) have led to the development of various
      immunologically oriented therapies for these diseases. The existence of elevated
      levels of tumor necrosis factor-alpha (TNF-alpha) in bone marrow during early
      stages of MDS, and the possibility that TNF- proportional, variant suppresses
      normal hematopoiesis led to studies of attempts to block the activity of TNF
      alpha. An anti-TNF monoclonal antibody and an antibody comprised of the soluble
      extracellular ligand-binding portion of the TNF receptor have both been evaluated
      recently in several small pilot studies. The recognition that marrow suppression
      in MDS may, in part, be a T-cell mediated autoimmune process has stimulated
      various trials of antithymocyte globulin and other similar agents. Gemtuzumab
      ozogamicin, an antibody against CD33 conjugated to the cytotoxic agent
      calicheamicin, is approved for use in AML and is currently being investigated as
      a potential therapeutic agent in MDS. Clinical trials were conducted as either
      monotherapy or in combination with cytokines such as IL-11 and chemotherapeutic
      agents including idarubicin, fludarabine, and/or cytarabine. Other antibodies are
      being developed as immunoconjugates with radioisotopes as part of conditioning
      regimens prior to bone marrow transplantation for AML or MDS. These include
      (131)I-anti-CD45 antibody (BC8), (131)I anti-CD33 antibody (p67), (213)Bi-M195
      antibody, and (188)Re-labeled anti-CD66 antibody. The clearest example of
      successful immunotherapy for MDS (and AML) is the use of the graft-versus-tumor
      effect associated with allogeneic hematopoietic cell transplantation. Recently,
      nonmyeloablative transplants have been explored with encouraging results.
      Vaccines using overexposed self-antigens such as WT1 and PR1 are other attempts
      to induce a T-cell mediated response against MDS.

PMID- 15494302
TI  - Proteoglycans make the grade-ient.
AB  - Two recent reports in Developmental Cell reveal further insights into the complex
      mechanisms by which heparan sulfate proteoglycans provide organisms with novel
      ways of generating and interpreting morphogen gradients.

PMID- 15494303
TI  - Knowing when to let go: endosomal release of LDL from the LDL-Receptor.
AB  - In this issue of Molecular Cell, Blacklow and colleagues use NMR structural
      analyses and the combination of deletion mapping, site-directed mutagenesis and
      LDL release assays to examine the molecular basis for low pH-induced release of
      LDL from the LDL receptor.

PMID- 15494304
TI  - Mismatch recognition and uracil excision provide complementary paths to both Ig
      switching and the A/T-focused phase of somatic mutation.
AB  - AID-mediated deamination of dC residues within the immunoglobulin locus generates
      dU:dG lesions whose resolution leads to class-switch recombination and somatic
      hypermutation. The dU:dG pair is a mismatch and comprises a base foreign to DNA
      and is, thus, recognized by proteins from both base excision (uracil-DNA
      glycosylase, UNG) and mismatch recognition (MSH2/MSH6) pathways. Strikingly,
      while antibody diversification is perturbed by single deficiency in either UNG or
      MSH2, combined UNG/MSH2 deficiency leads to a total ablation both of switch
      recombination and of IgV hypermutation at dA:dT pairs. The initiating dU:dG
      lesions appear not to be recognized and are simply replicated over. The results
      indicate that the major pathway for switch recombination occurs through uracil
      excision with mismatch recognition of dU:dG providing a backup; the second phase
      of hypermutation (essentially introducing mutations solely at dA:dT pairs) is
      triggered by mismatch recognition of the dU:dG lesion with uracil excision
      providing a backup.

PMID- 15494305
TI  - Mcm10 regulates the stability and chromatin association of DNA polymerase-alpha.
AB  - Mcm10 is a conserved eukaryotic DNA replication factor whose function has
      remained elusive. We report here that Mcm10 binding to replication origins in
      budding yeast is cell cycle regulated and dependent on the putative helicase,
      Mcm2-7. Mcm10 is also an essential component of the replication fork. A fraction
      of Mcm10 binds to DNA, as shown by histone association assays that allow for the
      study of chromatin binding in vivo. However, Mcm10 is also required to maintain
      steady-state levels of DNA polymerase-alpha (polalpha). In temperature-sensitive
      mcm10-td mutants, depletion of Mcm10 during S phase results in degradation of the
      catalytic subunit of polalpha, without affecting other fork components such as
      Cdc45. We propose that Mcm10 stabilizes polalpha and recruits the complex to
      replication origins. During elongation, Mcm10 is required for the presence of
      polalpha at replication forks and may coordinate DNA synthesis with DNA unwinding
      by the Mcm2-7 complex.

PMID- 15494306
TI  - Selective regulation of vitamin D receptor-responsive genes by TFIIH.
AB  - Mutations in the XPD subunit of the transcription/repair factor TFIIH cause the
      Xeroderma pigmentosum disorder. We show that in some XP-D deficient cells,
      transactivation by the vitamin D receptor (VDR) is selectively inhibited for a
      subset of responsive genes, such as CYP24, and that the XPD/R683W mutation
      prevents VDR recruitment on its promoter. Contrary to other nuclear receptors,
      VDR, which lacks a functional A/B domain, is not phosphorylated and consequently
      not regulated by the cdk7 kinase of TFIIH. In fact, we demonstrate that the VDR
      transactivation defect resides in Ets1, another activator that cannot be
      phosphorylated by TFIIH in XP-D cells. Indeed, the phosphorylated Ets1 seems to
      promote the binding of VDR to its responsive element and trigger the subsequent
      recruitment of coactivators and RNA pol II. We propose a model in which TFIIH
      regulates the activity of nuclear receptors by phosphorylating either their A/B
      domain or an additional regulatory DNA binding partner.

PMID- 15494308
TI  - How an RNA ligase discriminates RNA versus DNA damage.
AB  - T4 RNA ligase 2 (Rnl2) exemplifies a family of RNA-joining enzymes that includes
      protozoan RNA-editing ligases. Rnl2 efficiently seals 3'-OH/5'-PO4 RNA nicks in
      either a duplex RNA or an RNA:DNA hybrid but cannot seal DNA nicks. RNA
      specificity arises from a requirement for at least two ribonucleotides
      immediately flanking the 3'-OH of the nick; the rest of the nicked duplex can be
      replaced by DNA. The terminal 2'-OH at the nick is important for the attack of
      the 3'-OH on the 5'-adenylated strand to form a phosphodiester, but dispensable
      for nick recognition and adenylylation of the 5'-PO4 strand. The penultimate 2'
      OH is important for nick recognition. Stable binding of Rnl2 at a nick depends on
      contacts to both the N-terminal adenylyltransferase domain and its signature C
      terminal domain. Nick sensing also requires adenylylation of Rnl2. These results
      provide insights to the evolution of nucleic acid repair systems.

PMID- 15494307
TI  - Global position and recruitment of HATs and HDACs in the yeast genome.
AB  - Chromatin regulators play fundamental roles in the regulation of gene expression
      and chromosome maintenance, but the regions of the genome where most of these
      regulators function has not been established. We explored the genome-wide
      occupancy of four different chromatin regulators encoded in Saccharomyces
      cerevisiae. The results reveal that the histone acetyltransferases Gcn5 and Esa1
      are both generally recruited to the promoters of active protein-coding genes. In
      contrast, the histone deacetylases Hst1 and Rpd3 are recruited to specific sets
      of genes associated with distinct cellular functions. Our results provide new
      insights into the association of histone acetyltransferases and histone
      deacetylases with the yeast genome, and together with previous studies, suggest
      how these chromatin regulators are recruited to specific regions of the genome.

PMID- 15494309
TI  - Coupled in vitro import of U snRNPs and SMN, the spinal muscular atrophy protein.
AB  - Cytoplasmic assembly of Sm-class small nuclear ribonucleoproteins (snRNPs) is a
      central process in eukaryotic gene expression. A large macromolecular complex
      containing the survival of motor neurons (SMN) protein is required for proper
      snRNP assembly in vivo. Defects in SMN function lead to a human neuromuscular
      disorder, spinal muscular atrophy (SMA). SMN protein localizes to both nuclear
      and cytoplasmic compartments, and a reduction in nuclear levels of SMN is
      correlated with the disease. The mechanism of SMN nuclear import, however, is
      unknown. Using digitonin-permeabilized cells, we show that SMN import depends on
      the presence of Sm snRNPs. Conversely, import of labeled U1 snRNPs was SMN
      complex dependent. Thus, import of SMN and U snRNPs are coupled in vitro.
      Furthermore, we identify nuclear import defects in SMA patient-derived SMN
      mutants, uncovering a potential mechanism for SMN dysfunction.

PMID- 15494310
TI  - Modulation of transcription affects mRNP quality.
AB  - Cotranscriptional loading of proteins onto nascent transcripts contributes to the
      formation of messenger ribonucleoprotein particles (mRNPs) competent for nuclear
      export. The transcription machinery is believed to play a pivotal role in mRNP
      assembly, which is at least partially linked to the function of the THO/TREX
      complex and the mRNA termination/polyadenylation apparatus. Here we demonstrate a
      prominent role for the rate of transcription in the production of export
      competent mRNPs. We show that a transcription-defective allele of the Rad3p
      helicase, a component of the TFIIH transcription initiation factor, suppresses
      several phenotypes associated with defective mRNA processing and export.
      Strikingly, the effects of compromised Rad3p activity can be phenocopied by a
      transcription elongation drug as well as by other mutations affecting
      transcription. Our results suggest that efficient mRNP assembly is under a
      kinetic control that is influenced by the rate of transcription.

PMID- 15494311
TI  - SMRT derepression by the IkappaB kinase alpha: a prerequisite to NF-kappaB
      transcription and survival.
AB  - Understanding how signaling cascades stimulate chromatin-remodeling events
      through derepression is one of the foremost questions in the transcription field.
      Here, we demonstrate that NF-kappaB transcription requires IKKalpha to
      phosphorylate SMRT on chromatin, stimulating the exchange of corepressor for
      coactivator complexes. IKKalpha-induced phosphorylation coincides with a loss of
      chromatin-associated SMRT and HDAC3 and with nuclear export of the SMRT
      corepressor, events required for expression of the NF-kappaB-regulated cIAP-2 and
      IL-8 genes. Although SMRT derepression corresponds with the recruitment of
      TBL1/TBLR1, this complex alone is insufficient to relieve repression. Using a
      nonphosphorylatable SMRT protein, we demonstrate that IKKalpha-induced
      phosphorylation is required to recruit 14-3-3epsilon and Ubc5 for SMRT
      derepression. Failure of IKKalpha to stimulate the removal of SMRT from chromatin
      inhibits the recruitment of NF-kappaB to promoters, blocking transcription and
      sensitizing cells to apoptosis. Our work provides evidence that IKKalpha
      orchestrates SMRT derepression, a prerequisite for NF-kappaB transcription and
      survival.

PMID- 15494312
TI  - Paxillin serves as an ERK-regulated scaffold for coordinating FAK and Rac
      activation in epithelial morphogenesis.
AB  - Activation of the hepatocyte growth factor (HGF) receptor in epithelial cells
      results in lamellipodia protrusion, spreading, migration, and tubule formation.
      We have previously reported that these morphogenic effects are dependent on MAPK
      activation at focal adhesions. In the present study we demonstrate that activated
      ERK phosphorylates paxillin on serine 83 and that mutation of this site
      eliminates HGF-stimulated increased association of paxillin and FAK in
      subconfluent cells. Failure to activate FAK at focal adhesions results in a loss
      of FAK-PI 3-kinase association and the marked reduction of Rac activation after
      HGF stimulation. Expression of paxillin mutants that disrupt ERK association or
      phosphorylation inhibits HGF-induced cell spreading, migration, and
      tubulogenesis. These data demonstrate that the paxillin-MAPK complex serves as a
      central regulator of HGF-stimulated FAK and Rac activation in the vicinity of
      focal adhesions, thus promoting the rapid focal adhesion turnover and
      lamellipodia extension that are required for migratory and tubulogenic responses.

PMID- 15494313
TI  - Critical conformational changes in the Arp2/3 complex are induced by nucleotide
      and nucleation promoting factor.
AB  - Actin nucleation and branching by the Arp2/3 complex is tightly regulated by
      activating factors. However, the mechanism of Arp2/3 complex activation remains
      unclear. We used fluorescence resonance energy transfer (FRET) to probe the
      conformational dynamics of the Arp2/3 complex accompanying its activation. We
      demonstrate that nucleotide binding promotes a substantial conformational change
      in the complex, with distinct conformations depending on the bound nucleotide.
      Nucleotide binding to each Arp is critical for activity and is coupled to
      nucleation promoting factor (NPF) binding. The binding of Wiskott-Aldrich
      syndrome protein (WASP) family NPFs induces further conformational reorganization
      of the Arp2/3 complex, and the ability to promote this conformational
      reorganization correlates with activation efficiency. Using an Arp2/3 complex
      that is fused to the actin binding domain of WASP, we confirm that the NPF
      induced conformational change is critical for activation, and that the actin and
      Arp2/3 binding activities of WASP are separable, but are independently essential
      for activity.

PMID- 15494314
TI  - Cooperation between fixed and low pH-inducible interfaces controls lipoprotein
      release by the LDL receptor.
AB  - Low-density lipoprotein (LDL) receptors bind lipoprotein particles at the cell
      surface and release them in the low pH environment of the endosome. The published
      structure of the receptor determined at endosomal pH reveals an interdomain
      interface between its beta propeller and its fourth and fifth ligand binding (LA)
      repeats, suggesting that the receptor adopts a closed conformation at low pH to
      release LDL. Here, we combine lipoprotein binding and release assays with NMR
      spectroscopy to examine structural features of the receptor promoting release of
      LDL at low pH. These studies lead to a model in which the receptor uses a pH
      invariant scaffold as an anchor to restrict conformational search space,
      combining it with flexible linkers between ligand binding repeats to interconvert
      between open and closed conformations. This finely tuned balance between
      interdomain rigidity and flexibility is likely to represent a shared structural
      feature in proteins of the LDL receptor family.

PMID- 15494315
TI  - Glucose and sucrose act as agonist and mannose as antagonist ligands of the G
      protein-coupled receptor Gpr1 in the yeast Saccharomyces cerevisiae.
AB  - Several examples of G protein-coupled receptors have recently been suggested to
      respond to common sugars in millimolar concentrations. This low affinity has made
      it difficult to demonstrate direct receptor-ligand interaction. In the yeast
      Saccharomyces cerevisiae, rapid activation of the cAMP pathway by glucose and
      sucrose requires the GPCR Gpr1. Our results obtained by cysteine scanning
      mutagenesis and SCAM (substituted cysteine accessibility method) of residues in
      TMD VI provide strong evidence that glucose and sucrose directly interact as
      ligands with Gpr1. The affinity for sucrose is much higher. Structurally similar
      sugars such as galactose, mannose, and fructose do not act as agonists, but
      mannose acts as an antagonist for both sucrose and glucose. These results support
      the idea that Gpr1 directly senses sugars and that sugars can effectively bind
      GPCRs with a low affinity in a binding pocket formed by the transmembrane
      domains. The ligand repertoire of GPCRs can thus be extended to common sugars in
      millimolar concentrations.

PMID- 15494316
TI  - Structure of EthR in a ligand bound conformation reveals therapeutic perspectives
      against tuberculosis.
AB  - Mycobacterium tuberculosis EthR is a repressor of ethA, a gene encoding a mono
      oxygenase required for the activation of the prodrug ethionamide. Here we
      describe the X-ray crystal structure of EthR, a homodimer with an entirely
      helical structure showing similarities to TetR family members. Each monomer
      contained a fortuitous ligand identified as hexadecyl octanoate. The crystal
      structure of EthR purified in M. smegmatis revealed the presence of a comparable
      ligand. The binding of hexadecyl octanoate to EthR induces a conformational state
      incompatible with repressor function, which should lead to ethA derepression and
      consequently to an increased sensitivity to ethionamide and other thioamides. A
      related, more hydrophilic ketone was found to exhibit synergistic
      antimycobacterial effects when tested together with ethionamide, indicating that
      this strategy may help reduce the dosage of potent antibacterial compounds that
      otherwise are too toxic to be used as first-line drugs.

PMID- 15494317
TI  - Retroviral pseudotransduction for targeted cell manipulation.
AB  - The present study addressed whether retroviral vectors could be modified to
      achieve receptor-mediated, dose-controlled, and transient delivery of proteins or
      nucleic acids into targeted cells. As a paradigm, we generated mouse leukemia
      virus-based vectors encoding the site-specific recombinase Cre. The vectors were
      disabled in primer binding site function, blocking reverse transcription of the
      virion mRNA. While reducing transgene insertion more than 1000-fold and
      abolishing toxic effects of constitutive Cre expression, transient Cre delivery
      was still highly efficient, receptor restricted, and insensitive to pharmacologic
      inhibition of reverse transcription. This form of Cre transfer required the
      retroviral packaging signal, cap-proximal positioning of the translation unit, as
      well as gag and env expression in producer cells, revealing retroviral mRNA
      transfer as the underlying mechanism. Thus, retrovirally delivered mRNA may serve
      as an immediate translation template if not being reverse transcribed. This
      approach allows multiple modifications for targeted and reversible cell
      manipulation with nucleic acids.

PMID- 15494318
TI  - Nuclear-cytoplasmic shuttling of the oncogenic mouse UNP/USP4 deubiquitylating
      enzyme.
AB  - The oncogenic deubiquitylating enzyme (DUB) Unp/Usp4, which binds to the
      retinoblastoma family of tumor suppressor proteins, was originally described as a
      nuclear protein. However, more recent studies have shown it to be cytoplasmic. In
      addition, analysis of its subcellular localization has been complicated by the
      existence of the paralog Usp15. In this study, we resolved this controversy by
      investigating the localization of exogenously expressed Usp4 (using red
      fluorescent protein-Usp4) and of endogenous Usp4 (using highly specific
      antibodies that can distinguish Usp4 from Usp15). We found that by inhibiting
      nuclear export with leptomycin B, both exogenous and endogenous Usp4 accumulate
      in the nucleus. Further, using a Rev-green fluorescent protein-based export
      assay, we confirmed the existence of a nuclear export signal
      ((133)VEVYLLELKL(142)) in Usp4. In addition, a functional nuclear import signal
      ((766)QPQKKKK(772)) was also identified, which was specifically recognized by
      importin alpha/beta. Finally, we show that the equilibrium of Usp4 subcellular
      localization varies between different cell types. Usp4 is thus the first DUB
      reported to have nucleocytoplasmic shuttling properties. The implications of this
      shuttling for its function as a DUB are discussed.

PMID- 15494319
TI  - Mitogen-activated protein kinases and mitogen-activated protein kinase
      phosphatases mediate the inhibitory effects of all-trans retinoic acid on the
      hypertrophic growth of cardiomyocytes.
AB  - All-trans retinoic acid (RA) has been implicated in mediation of cardiac growth
      inhibition in neonatal cardiomyocytes. However, the associated signaling
      mechanisms remain unclear. Utilizing neonatal cardiomyocytes, we demonstrated
      that RA suppressed the hypertrophic features induced by cyclic stretch or
      angiotensin II (Ang II). Cyclic stretch- or Ang II-induced activation of
      extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase
      (JNK), and p38 mitogen-activated protein kinase (MAP kinase) was dose- and time
      dependently inhibited by RA. Significant inhibition was observed by 5 microm RA,
      from 8 to 24 h of pretreatment. This inhibitory effect was not mediated at the
      level of mitogen-activated protein kinase kinases (MKKs), because RA had no
      effect on stretch- or Ang II-induced phosphorylation of MEK1/2, MKK4, and MKK3/6.
      However, the phosphatase inhibitor vanadate reversed the inhibitory effect of RA
      on MAP kinases and protein synthesis. RA up-regulated the expression level of MAP
      kinase phosphatase-1 (MKP-1) and MKP-2, and the time course was correlated with
      the inhibitory effect of RA on activation of MAP kinases. Overexpression of wild
      type MKP-1 inhibited the phosphorylation of JNK and p38 in cardiomyocytes. These
      data indicated that MKPs were involved in the inhibitory effect of RA on MAP
      kinases. Using specific RAR and RXR antagonists, we demonstrated that both RARs
      and RXRs were involved in regulating stretch- or Ang II-induced activation of MAP
      kinases. Our findings provide the first evidence that the anti-hypertrophic
      effect of RA is mediated by up-regulation of MKPs and inhibition of MAP kinase
      signaling pathways.

PMID- 15494320
TI  - Law & psychiatry: "One madman keeping loaded guns": misconceptions of mental
      illness and their legal consequences.

PMID- 15494321
TI  - What is normal?

PMID- 15494322
TI  - Evidence of subclinical medial collateral ligament injury and posteromedial
      impingement in professional baseball players.
AB  - BACKGROUND: Recognition and treatment of elbow conditions such as medial
      collateral ligament injury and posteromedial impingement are increasing in
      throwing athletes. Magnetic resonance imaging may provide pivotal information in
      the management of these athletes. Knowledge of the utility of magnetic resonance
      imaging has become widespread throughout the baseball community. However, data on
      the frequency and extent of asymptomatic magnetic resonance imaging findings in
      the elbows of this throwing population are lacking . HYPOTHESIS: Abnormalities in
      the throwing elbows of asymptomatic professional baseball players compared to the
      nonthrowing elbows are frequently seen in magnetic resonance images. STUDY
      DESIGN: Descriptive anatomical study. METHODS: Sixteen asymptomatic professional
      baseball players with no history of injury underwent bilateral elbow magnetic
      resonance imaging using a standardized sequencing protocol. The magnetic
      resonance images were reviewed, in a blinded fashion, by 2 musculoskeletal
      radiologists and 1 orthopaedic surgeon. RESULTS: Medial collateral ligament
      abnormalities (including thickening, signal heterogeneity, or discontinuity) were
      present in 87% of players' dominant elbows. Findings consistent with
      posteromedial impingement were present in 13 of 16 subjects. There was a
      significant correlation between medial collateral ligament thickening and
      posteromedial subchondral sclerosis (P = .04). The throwing elbow was correctly
      identified in all 16 subjects. No significant correlation between magnetic
      resonance imaging findings and age could be detected. CONCLUSIONS: This study
      demonstrates a high rate of abnormal magnetic resonance imaging findings in
      asymptomatic throwers' elbows. These baseline findings must be considered when
      magnetic resonance imaging is being used as a factor in treatment decisions.

PMID- 15494323
TI  - Elbow medial ulnar collateral ligament insufficiency alters posteromedial
      olecranon contact.
AB  - BACKGROUND: The effect of elbow medial ulnar collateral ligament injury on
      posteromedial compartment contact is unknown. HYPOTHESIS: Medial ulnar collateral
      ligament injury causes altered contact area and pressure in the posteromedial
      compartment of the elbow. STUDY DESIGN: Controlled laboratory study. METHODS:
      Seven elbow cadaveric specimens were tested in an apparatus that positioned the
      elbow at 30 degrees and 90 degrees of flexion. Partial and full tears were
      simulated by releasing the medial ulnar collateral ligament. Pressure-sensitive
      film was placed in the posteromedial compartment for each condition. Valgus
      torques of 1.25 and 2.0 N.m were applied for each ligament condition, and
      kinematic data were obtained at each flexion angle using a 3-dimensional
      digitizer. RESULTS: Both ligament condition and valgus load had significant
      effects on contact area and pressure (P<.05). For a given load and flexion angle,
      the contact area decreased and the pressure increased with increasing medial
      ulnar collateral ligament insufficiency. Within these trends, statistical
      significance was found at 30 degrees of elbow flexion for both area and pressure
      (P<.05); at 90 degrees of elbow flexion, increasing medial ulnar collateral
      ligament insufficiency did not significantly affect contact area or pressure
      (P>.05). DISCUSSION: Medial ulnar collateral ligament insufficiency alters
      contact area and pressure between the posteromedial trochlea and olecranon and
      helps explain the development of posteromedial osteophytes.

PMID- 15494324
TI  - The effect of estrogen on ovine anterior cruciate ligament fibroblasts: cell
      proliferation and collagen synthesis.
AB  - Estrogen has been implicated as a causal factor for anterior cruciate ligament
      injuries in women. Studies have demonstrated a decrease in anterior cruciate
      ligament fibroblast proliferation and collagen synthesis at supraphysiologic
      levels of estrogen in a rabbit model. HYPOTHESIS: The authors hypothesized that
      physiologic levels of estrogen would have no significant effect on anterior
      cruciate ligament fibroblast proliferation and collagen synthesis in an ovine
      model. METHODS: Anterior cruciate ligament fibroblasts were isolated from sheep
      knees using routine cell culture methods. The cells were exposed to 17beta
      estradiol at physiologic concentrations of 2.2, 5, 15, 25, 250, and 2500 pg/ml.
      Cell proliferation was determined by cell counts on days 4 and 6. Collagen
      synthesis was determined by (3)H-proline incorporation on day 4.
      Immunohistochemistry was performed to detect estrogen receptors. RESULTS:
      Immunohistochemistry demonstrated the presence of estrogen receptors in ovine
      anterior cruciate ligament fibroblasts. There was no significant difference in
      anterior cruciate ligament fibroblast proliferation or collagen synthesis
      regardless of 17beta-estradiol concentration. CONCLUSIONS: Based on results of
      this study, and given the low turnover of collagen in ligaments, it is unlikely
      that a 2- to 3-day per month increase in circulating estrogen would result in
      rapid, clinically significant alterations in material properties of the anterior
      cruciate ligament in vivo. The etiology of noncontact anterior cruciate ligament
      injuries is complex and multifactorial in nature, meriting further investigation.

PMID- 15494325
TI  - Bone morphogenetic protein-7 (osteogenic protein-1) promotes tendon graft
      integration in anterior cruciate ligament reconstruction in sheep.
AB  - BACKGROUND: Bone morphogenetic proteins induce new bone both in patients with
      bone defects and at extraskeletal sites in animals. After anterior cruciate
      ligament rupture, tendon graft fixation into a bone tunnel is a widely used
      method for anterior cruciate ligament reconstruction. HYPOTHESIS: Bone
      morphogenetic protein-7 applied to the bone-tendon interface enables better
      integration of a free tendon graft into the surrounding bone. STUDY DESIGN:
      Controlled laboratory study. METHODS: The anterior cruciate ligament was
      reconstructed using a free tendon graft in the right rear knees of 30 one-year
      old male sheep. Recombinant human bone morphogenetic protein-7 (25 microg) was
      applied randomly to the bone-tendon interface in 15 animals, and a vehicle was
      applied in 15 control animals. At 3 weeks, 10 animals from each group were
      sacrificed, and the remaining sheep were sacrificed at 6 weeks after surgery.
      Subsequently, histologic analysis and mechanical testing were performed. In
      another group of 20 sheep, the same procedure was used and mechanical testing was
      performed after 3 weeks. RESULTS: More new bone was formed at the bone-tendon
      interface in the knees treated with bone morphogenetic protein-7 as compared
      histologically with similar areas in control animals, creating areas of dense
      trabecular network with significantly greater invasion of the tendon fibrous
      tissue into the bone marrow space. Mechanical testing showed greater strain
      resistance to force (368 N) in the knees treated with bone morphogenetic protein
      7 than in control specimens (214 N). There was no difference between mechanical
      testing of samples from 3 and 6 weeks after surgery. CONCLUSION: Bone
      morphogenetic protein-7 promotes complete tendon graft integration into the newly
      formed surrounding trabecular bone in the reconstruction of the anterior cruciate
      ligament. CLINICAL RELEVANCE: Bone morphogenetic protein-7 in tendon graft
      integration might be successfully used in reconstructive surgery of ligaments.

PMID- 15494326
TI  - Incidence, causes, and severity of high school football injuries on FieldTurf
      versus natural grass: a 5-year prospective study.
AB  - BACKGROUND: Numerous injuries have been attributed to playing on artificial turf.
      Recently, FieldTurf was developed to duplicate the playing characteristics of
      natural grass. No long-term study has been conducted comparing game-related, high
      school football injuries between the 2 playing surfaces. HYPOTHESIS: High school
      athletes would not experience any difference in the incidence, causes, and
      severity of game-related injuries between FieldTurf and natural grass. STUDY
      DESIGN: Prospective cohort study. METHODS: A total of 8 high schools were
      evaluated over 5 competitive seasons for injury incidence, injury category, time
      of injury, injury time loss, player position, injury mechanism, primary type of
      injury, grade and anatomical location of injury, type of tissue injured, head and
      knee trauma, and environmental factors. RESULTS: Findings per 10 team games
      indicated total injury incidence rates of 15.2 (95% confidence interval, 13.7
      16.4) versus 13.9 (95% confidence interval, 11.9-15.6). Minor injury incidence
      rates of 12.1 (95% confidence interval, 10.5-13.6) versus 10.7 (95% confidence
      interval, 8.7-12.7), substantial injury incidence rates of 1.9 (95% confidence
      interval, 1.4-2.6) versus 1.3 (95% confidence interval, 0.8-2.1), and severe
      injury incidence rates of 1.1 (95% confidence interval, 0.7-1.7) versus 1.9 (95%
      confidence interval 1.2-2.8) were documented on FieldTurf versus natural grass,
      respectively. Multivariate analyses indicated significant playing surface effects
      by injury time loss, injury mechanism, anatomical location of injury, and type of
      tissue injured. Higher incidences of 0-day time loss injuries, noncontact
      injuries, surface/epidermal injuries, muscle-related trauma, and injuries during
      higher temperatures were reported on FieldTurf. Higher incidences of 1- to 2-day
      time loss injuries, 22+ days time loss injuries, head and neural trauma, and
      ligament injuries were reported on natural grass. CONCLUSIONS: Although
      similarities existed between FieldTurf and natural grass over a 5-year period of
      competitive play, both surfaces also exhibited unique injury patterns that
      warrant further investigation.

PMID- 15494327
TI  - Isokinetic evaluation of internal/external tibial rotation strength after the use
      of hamstring tendons for anterior cruciate ligament reconstruction.
AB  - BACKGROUND: Evaluation of the knee after an anterior cruciate ligament
      reconstruction with the use of the semitendinosus and gracilis (hamstring)
      autografts has primarily focused on flexion and extension strength. The
      semitendinosus and gracilis muscles contribute to internal tibial rotation, and
      it has been suggested that harvest of these tendons for the purpose of an
      anterior cruciate ligament reconstruction contributes to internal tibial rotation
      weakness. HYPOTHESIS: Internal tibial rotation strength may be affected by the
      semitendinosus and gracilis harvest after anterior cruciate ligament
      reconstruction. STUDY DESIGN: Prospective evaluation of internal and external
      tibial rotation strength. METHODS: Inclusion criteria for subjects (N = 30):
      unilateral anterior cruciate ligament reconstruction at least 2 years previously,
      a stable anterior cruciate ligament (<5-mm side-to-side difference) at time of
      testing confirmed by surgeon and KT-1000 arthrometer, no history of knee problems
      after initial knee reconstruction, a normal contralateral knee, and the ability
      to comply with the testing protocol. In an attempt to minimize unwanted subtalar
      joint motion, subjects were immobilized using an ankle brace and tested at
      angular velocities of 60 degrees /s, 120 degrees /s, and 180 degrees /s at a knee
      flexion angle of 90 degrees . RESULTS: The mean peak torque measurements for
      internal rotation strength of the operative limb (60 degrees /s, 17.4 +/- 4.5 ft
      lb; 120 degrees /s, 13.9 +/- 3.3 ft-lb; 180 degrees /s, 11.6 +/- 3.0 ft-lb) were
      statistically different compared to the nonoperated limb (60 degrees /s, 20.5 +/-
      4.7 ft-lb; 120 degrees /s, 15.9 +/- 3.8 ft-lb; 180 degrees /s, 13.4 +/- 3.8 ft
      lb) at 60 degrees /s (P = .012), 120 degrees /s (P = .036), and 180 degrees /s (P
      = .045). The nonoperative limb demonstrated greater strength at all speeds. The
      mean torque measurements for external rotation were statistically similar when
      compared to the nonoperated limb at all angular velocities. CONCLUSIONS: We have
      shown through our study that patients who undergo surgical intervention to repair
      a torn anterior cruciate ligament with the use of autogenous hamstring tendons
      demonstrate with weaker internal tibial rotation postoperatively at 2 years when
      compared to the contralateral limb.

PMID- 15494328
TI  - Evaluation of hamstring strength and tendon regrowth after harvesting for
      anterior cruciate ligament reconstruction.
AB  - BACKGROUND: It is generally thought that tissue regeneration and good functional
      recovery can be expected after anterior cruciate ligament reconstruction using
      the hamstring tendons. However, persistent strength deficit in deep knee flexion
      has also been reported. HYPOTHESIS: Morphologic regeneration of the harvested
      hamstring tendon is not necessarily associated with its functional recovery.
      STUDY DESIGN: Retrospective follow-up study. METHOD: Twenty-eight patients who
      underwent anterior cruciate ligament reconstruction with hamstring graft were
      evaluated after a minimum period of 2 years. Status of tendon regrowth was
      assessed by magnetic resonance imaging. To specifically analyze the functional
      deficit after graft harvest, the isometric hamstring strength was examined in a
      sitting position at 90 degrees of flexion and a prone position at 90 degrees and
      110 degrees of flexion. Then, the strength data were correlated with the extent
      of tendon regeneration. RESULTS: In 22 of the 28 patients, a regrowth of the
      semitendinosus tendon was found, whereas regeneration of the gracilis tendon was
      observed in 13 patients. In the evaluation of hamstring strength, the isometric
      peak torque was reduced to 86.2%, 54.6%, and 49.1%, respectively, in the
      aforementioned 3 postures as compared with the contralateral side. CONCLUSIONS:
      Significant functional deficit of hamstring strength remains regardless of
      morphologic regeneration.

PMID- 15494329
TI  - Bone anchors or interference screws? A biomechanical evaluation for autograft
      ankle stabilization.
AB  - BACKGROUND: Autograft stabilization uses free semitendinosus tendon grafts to
      anatomically reconstruct the anterior talofibular ligament. Study aims were to
      evaluate the biomechanical properties of Mitek GII anchors compared with the
      Arthrex Bio-Tenodesis Screw for free tendon reconstruction of the anterior
      talofibular ligament. NULL HYPOTHESIS: There are no differences in load to
      failure and percentage specimen elongation at failure between the 2 methods.
      STUDY DESIGN: Controlled laboratory study using porcine models. METHODS: Sixty
      porcine tendon constructs were failure tested. Re-creating the pull of the
      anterior talofibular ligament, loads were applied at 70 degrees to the bones.
      Thirty-six tendons were fixed to porcine tali and tested using a single pull to
      failure; 10 were secured with anchors and No. 2 Ethibond, 10 with anchors and
      FiberWire, 10 with screws and Fiberwire, and 6 with partially gripped screws.
      Cyclic preloading was conducted on 6 tendons fixed by anchors and on 6 tendons
      fixed by screws before failure testing. Two groups of 6 components fixed to the
      fibula were also tested. RESULTS: The talus single-pull anchor group produced a
      mean load of 114 N and elongation of 37% at failure. The talus single-pull screw
      group produced a mean load of 227 N and elongation of 22% at failure (P <.05).
      Cyclic preloading at 65% failure load before failure testing produced increases
      in load and decreases in elongation at failure. Partially gripped screws produced
      a load of 133 N and elongation of 30% at failure. The fibula model produced
      significant increases in load to failure for both. The human anterior talofibular
      ligament has loads of 139 N at failure with instability occurring at 20%
      elongation. CONCLUSIONS: Interference screw fixation produced significantly
      greater failure strength and less elongation at failure than bone anchors.
      CLINICAL RELEVANCE: The improved biomechanics of interference screws suggests
      that these may be more suited to in vivo reconstruction of the anterior
      talofibular ligament than are bone anchors.

PMID- 15494330
TI  - Effectiveness of extracorporeal shock wave therapy in the treatment of previously
      untreated lateral epicondylitis: a randomized controlled trial.
AB  - BACKGROUND: Extracorporeal shock wave therapy is a relatively new therapy used in
      the treatment of chronic tendon-related pain. Few randomized controlled trials
      have been performed on it, and no studies have examined the effectiveness of
      extracorporeal shock wave therapy as a frontline therapy for tendon-related pain.
      HYPOTHESIS: Subjects treated with active extracorporeal shock wave therapy will
      have higher rates of treatment success than subjects treated with sham
      extracorporeal shock wave therapy. DESIGN: Double-blind randomized controlled
      trial. METHODS: Sixty subjects who had previously untreated lateral epicondylitis
      for less than 1 year and more than 3 weeks were included in this study. Subjects
      were randomly allocated to receive 1 session per week for 3 weeks of either sham
      or active extra-corporeal shock wave therapy. Subjects in the active therapy
      group received 2000 pulses (energy flux density, 0.03-0.17 mJ/mm(2)). All
      subjects were provided with a forearm-stretching program. After 8 weeks of
      therapy, subjects were classified as either treatment successes or treatment
      failures according to fulfillment of all 3 criteria: (1) at least a 50% reduction
      in the overall pain visual analog scale score, (2) a maximum allowable overall
      pain visual analog scale score of 4.0 cm, and (3) no use of pain medication for
      elbow pain for 2 weeks before the 8 week follow-up. Visual analog scale scores
      were also collected for pain at rest, during sleep, during activity, at its
      worst, and at its least, as well as for quality of life (using the EuroQoL
      questionnaire) and grip strength. RESULTS: Success rates in the sham and active
      therapy groups were 31% and 39%, respectively. No significant difference was
      detected between groups (chi(2)(1)= 0.3880, P = .533). Mean change in quality of
      life over 8 weeks was an increase of 1.3 and 3.3 for sham and active therapy
      groups, respectively, and mean change in grip strength over 8 weeks was an
      increase of 7.4 kg and 6.8 kg for sham and active therapy groups, respectively.
      CONCLUSIONS: Despite improvement in pain scores and pain-free maximum grip
      strength within groups, there does not appear to be a meaningful difference
      between treating lateral epicondylitis with extracorporeal shock wave therapy
      combined with forearm-stretching program and treating with forearm-stretching
      program alone, with respect to resolving pain within an 8-week period of
      commencing treatment.

PMID- 15494331
TI  - Diagnostic accuracy of clinical assessment, magnetic resonance imaging, magnetic
      resonance arthrography, and intra-articular injection in hip arthroscopy
      patients.
AB  - BACKGROUND: Hip arthroscopy has defined elusive causes of hip pain.
      HYPOTHESIS/PURPOSE: It is postulated that the reliability of various
      investigative methods is inconsistent. The purpose of this study is to evaluate
      the diagnostic accuracy of these methods. STUDY DESIGN: Retrospective review of
      prospectively collected data. METHODS: Five parameters were assessed in 40
      patients: clinical assessment, high-resolution magnetic resonance imaging,
      magnetic resonance imaging with gadolinium arthrography, intra-articular
      bupivacaine injection, and arthroscopy. Using arthroscopy as the definitive
      diagnosis, the other parameters were evaluated for reliability. RESULTS: Hip
      abnormality was clinically suspected in all cases with 98% accuracy (1 false
      positive). However, the nature of the abnormality was identified in only 13 cases
      with 92% accuracy. Magnetic resonance imaging variously demonstrated direct or
      indirect evidence of abnormality but overall demonstrated a 42% false-negative
      and a 10% false-positive interpretation. Magnetic resonance arthrography
      demonstrated an 8% false-negative and 20% false-positive interpretation. Response
      to the intra-articular injection of anesthetic was 90% accurate (3 false-negative
      and 1 false-positive responses) for detecting the presence of intra-articular
      abnormality. CONCLUSIONS: In this series, clinical assessment accurately
      determined the existence of intra-articular abnormality but was poor at defining
      its nature. Magnetic resonance arthrography was much more sensitive than magnetic
      resonance imaging at detecting various lesions but had twice as many false
      positive interpretations. Response to an intra-articular injection of anesthetic
      was a 90% reliable indicator of intra-articular abnormality.

PMID- 15494332
TI  - The effect of posterior cruciate ligament injury and reconstruction on meniscal
      strain.
AB  - BACKGROUND: The relationship between posterior cruciate ligament insufficiency
      and meniscal injury is unclear. HYPOTHESIS: Posterior cruciate ligament
      insufficiency results in increased medial and lateral meniscal strain. STUDY
      DESIGN: Descriptive anatomic study. METHODS: Eight cadaveric specimens were
      evaluated with a 6-axis load cell and differential variable reluctance transducer
      strain gauges placed in both menisci. Data were recorded in the posterior
      cruciate ligament-intact state after posterior cruciate ligament transection and
      after posterior cruciate ligament reconstruction. RESULTS: The effect of
      posterior cruciate ligament state on meniscal strain was more pronounced at
      higher flexion angles. At 60 degrees and 90 degrees of flexion, there was a
      significant effect of posterior cruciate ligament sectioning and reconstruction
      on meniscal strain (P < .026). Average meniscal strain for both medial and
      lateral menisci increased between the intact and the posterior cruciate ligament
      cut states. Posterior cruciate ligament reconstruction decreased strain values to
      that of the intact knee. CONCLUSIONS: Meniscal strain increases with complete
      posterior cruciate ligament injury and is returned to posterior cruciate ligament
      intact levels after posterior cruciate ligament reconstruction. CLINICAL
      RELEVANCE: Posterior cruciate ligament reconstruction may play an important role
      in reducing meniscal strain and subsequent degeneration within the posterior
      cruciate ligament-injured knee.

PMID- 15494333
TI  - Incidence and location of bone bruises after acute posterior cruciate ligament
      injury.
AB  - BACKGROUND: In patients suffering from an anterior cruciate ligament injury, the
      incidence and location of bone bruises are well documented. This study reports
      data regarding bone bruises after acute posterior cruciate ligament injury.
      HYPOTHESIS: Bone bruises associated with posterior cruciate ligament injury are
      common, and their location differs from those seen with anterior cruciate
      ligament injury. STUDY DESIGN: Retrospective cohort study. METHODS: Thirty-five
      consecutive patients were identified as having a grade II or III posterior
      cruciate ligament tear, with an intact anterior cruciate ligament, in which a
      magnetic resonance imaging scan had been obtained within 20 days of injury.
      Magnetic resonance imaging scans were reviewed to document bone bruises,
      associated medial or lateral ligamentous injury, and meniscal and chondral
      abnormalities. RESULTS: Of the 35 patients, 29 (83%) had a bone bruise in at
      least one location. Bone bruises were found throughout the joint, more widely
      dispersed than is commonly seen with anterior cruciate ligament injury. Also, 29
      patients had magnetic resonance imaging findings of associated ligamentous
      injury. Lateral bone bruises were associated with medial collateral ligament
      injury, whereas medial bone bruises correlated with posterolateral injury.
      CONCLUSIONS: The incidence of bone bruises associated with posterior cruciate
      ligament injury is similar to that seen with anterior cruciate ligament injury.
      Their location is more widely dispersed. The location of a bone bruise should
      lead to careful magnetic resonance imaging inspection and physical examination
      for ligamentous injury to the opposite side of the joint. Truly isolated
      posterior cruciate ligament injuries are rare, as most occur with osseous and
      some degree of associated ligamentous injury.

PMID- 15494334
TI  - Radiographic changes in the hands and fingers of young, high-level climbers.
AB  - BACKGROUND: In the past few years, competition climbing has grown in popularity,
      and younger people are being drawn to the sport. HYPOTHESIS: Although the
      radiographic changes in long-term climbers are known, there are little data
      available on young climbers. The question arises as to whether climbing at high
      levels at a young age leads to radiographic changes and possibly an early onset
      of osteoarthrosis in the finger joints. STUDY DESIGN: Cross-sectional study.
      METHODS: Nineteen members of the German Junior National Team and 18 recreational
      climbers were examined clinically and through radiographs. For comparison,
      radiographs of 12 young nonclimbers (control group) were collected. Radiographs
      were evaluated using a standard protocol. For evaluation of the physiologic
      adaptation, the cortical thickness of the middle phalanx and the Barnett Nordin
      index were analyzed. The results were compared between the 3 groups and against
      radiographs of 140 long-term, experienced climbers. RESULTS: Six climbers (32%)
      of the German Junior National Team presented a decreased range of motion for the
      small finger joints; none of the recreational climbers showed this decrease. In
      47% of the German Junior National Team and 28% of the recreational climbers,
      stress reactions could be found: cortical hypertrophy (26% German Junior National
      Team, 11% recreational climbers), subchondral sclerosis (47% German Junior
      National Team, 6% recreational climbers), broadened base of the proximal
      interphalangeal joint (42% German Junior National Team, 28% recreational
      climbers), and broadened base of the distal interphalangeal joint (16% German
      Junior National Team, 0 recreational climbers). Signs of an early stage of
      osteoarthrosis were seen in 1 climber in each group. The control group showed no
      radiologic abnormalities. The Barnett Nordin index was 0.49 +/- 0.05 in German
      Junior National Team, 0.49 +/- 0.07 in recreational climbers, and 0.48 +/- 0.08
      in the control group. There was no statistically significant difference on the
      Barnett Nordin index between the groups (German Junior National Team/recreational
      climbers: P = .89; German Junior National Team/control group: P = .58;
      recreational climbers/control group: P = .55). CONCLUSIONS: Intensive training
      and climbing lead to adaptive reactions; nevertheless, osteoarthrotic changes are
      rare.

PMID- 15494335
TI  - Force measurements on the fibular collateral ligament, popliteofibular ligament,
      and popliteus tendon to applied loads.
AB  - BACKGROUND: Little information is known about the forces seen on the main
      individual structures of the posterolateral knee to applied loads. This
      information is needed to determine which structures should be reconstructed and
      also the relative strengths needed for reconstruction grafts. PURPOSE: To
      determine in vitro forces in the fibular collateral ligament, popliteofibular
      ligament, and popliteus tendon for various posterolateral knee loading
      conditions. STUDY DESIGN: Cadaveric study. RESULTS: The fibular collateral
      ligament was loaded in varus, internal rotation, and external rotation. The
      highest amount of force seen on the fibular collateral ligament was at 0 degrees
      of knee flexion with external rotation, with the mean load response to external
      rotation significantly less at 90 degrees . Fibular collateral ligament varus
      load response at 0 degrees , 30 degrees , and 60 degrees was fairly constant,
      with a significant decrease at 90 degrees compared to 30 degrees of knee flexion.
      The popliteus tendon and popliteofibular ligament were loaded with an external
      rotation moment and were noted to have similar loading patterns. The mean load
      response on both the popliteus tendon and the popliteofibular ligament peaked at
      60 degrees of knee flexion. The mean popliteus tendon and popliteofibular
      ligament load response at 0 degrees was significantly less than the mean load
      response at 30 degrees , 60 degrees , and 90 degrees of knee flexion.
      CONCLUSIONS: High relative loads were seen on the fibular collateral ligament
      with varus and external rotation and on the popliteus tendon and popliteofibular
      ligament, with external rotation. A reciprocal relationship of load sharing in
      external rotation depending on knee flexion angle was revealed that has not been
      previously reported. The force on the fibular collateral ligament with external
      rotation loads was higher than the load on the popliteus complex at lower flexion
      angles, with the popliteus complex having higher load sharing at 60 degrees and
      90 degrees of knee flexion. These results provide a measure of the potential for
      failure of these structures with joint loading and guidelines for both graft
      strength requirements for surgical reconstructions and postoperative
      rehabilitation protocols.

PMID- 15494336
TI  - Gravity reduces the tibia when using a tibial guide that targets the
      intercondylar roof.
AB  - BACKGROUND: Reduction of the tibia relative to the femur with the knee in maximum
      extension is required to correctly position the tibial tunnel in the sagittal
      plane when using a guide that targets the intercondylar roof. The authors found
      no studies that determined (1) whether gravity reduces the tibia and (2) whether
      roof impingement is prevented without a roofplasty and without positioning the
      tibial tunnel too posteriorly. METHODS: The position of the tibia relative to the
      femur was measured from a lateral radiograph of the treated knee in maximum
      extension with and without the tibial guide and of the contralateral normal knee
      in extension in single-leg stance (control). RESULTS: The position of the tibia
      with and without the tibial guide was not different (P = .33, not significant)
      and was only 0.7 mm more posterior than the control knee (P = .0075). A
      roofplasty was not required, and the clearance was 2 mm or less. CONCLUSION:
      Gravity reduces the tibia on the femur when using a guide that targets the
      intercondylar roof. The use of a tibial guide that targets the intercondylar roof
      prevents roof impingement without a roofplasty and without positioning the tibial
      tunnel too posteriorly.

PMID- 15494337
TI  - Quantitative assessment of glenohumeral translation in baseball players: a
      comparison of pitchers versus nonpitching athletes.
AB  - BACKGROUND: Objective data quantifying differences in glenohumeral range of
      motion in baseball pitchers versus position players are established. There is
      limited information objectively comparing glenohumeral laxity in this same
      population. HYPOTHESIS: Baseball pitchers have greater difference in side-to-side
      anteroposterior translation of their throwing shoulders compared with position
      players. STUDY DESIGN: Prospective cross-sectional study. METHODS: Cutaneous
      electromagnetic sensors quantified anteroposterior shoulder translation of
      college and professional baseball players. Range of motion was measured. RESULTS:
      Nineteen position players and 37 pitchers were studied. Pitchers had a
      significant increase in external rotation of the dominant arm as compared with
      the nondominant arm (P = .02); the difference was not significant in position
      players (P = .34). The mean range of motion for pitchers' dominant arm was 110
      degrees external rotation to 68 degrees internal rotation, and it was 100 degrees
      external rotation to 85 degrees internal rotation for position players (P =
      .278). The mean anteroposterior translation in pitchers' dominant arm was 33.30
      mm and 29.84 mm in the nondominant side (P = .0001). This difference was not
      present in position players (P = .88). One of 19 position players had a side-to
      side shoulder translation difference greater than 3 mm, compared with 22 of 37
      pitchers (P = .0001). CONCLUSIONS: Pitchers have a greater amount of glenohumeral
      translation in the dominant arm. This difference is not seen in position players.
      These differences make the side-to-side comparison less useful in pitchers and
      should be considered when making therapeutic decisions.

PMID- 15494338
TI  - Prospective evaluation of the effect of rotator cuff integrity on the outcome of
      open rotator cuff repairs.
AB  - BACKGROUND: Open rotator cuff repairs have led to excellent clinical results;
      however, several studies have linked postoperative structural integrity to
      patient outcomes. The purpose of this study is to prospectively assess
      postoperative cuff integrity after open rotator cuff repair and assess its
      relationship to clinical outcome. HYPOTHESIS: Preoperative rotator cuff tear size
      and postoperative rotator cuff integrity are important factors in overall
      clinical outcomes. STUDY DESIGN: Prospective nonrandomized clinical outcomes
      study. METHODS: Forty-seven consecutive patients undergoing repair of full
      thickness rotator cuff tears by a single surgeon were enrolled in this
      prospective study. A standardized evaluation was performed preoperatively and
      postoperatively at annual intervals. All patients underwent postoperative
      magnetic resonance imaging at least 1 year after surgery. Statistical evaluation
      was performed using paired and unpaired 2-tailed t tests for comparison. RESULTS:
      Thirty-two patients were available for evaluation. Overall, the patients
      experienced a significant (P < .05) improvement in their American Shoulder and
      Elbow Surgeons survey (40-85) and Constant (53-80) scores. The overall retear
      rate was 31%. Although patients with large tears preoperatively and retears
      postoperatively had lower overall outcomes scores, this was not significant.
      CONCLUSION: These data support open rotator cuff repair as an effective technique
      that restores excellent shoulder function. The authors did not find postoperative
      cuff integrity to have a significant effect on outcomes when compared with those
      with an intact cuff. In fact, those with a retear still had a significant
      improvement in all clinical areas assessed, including strength.

PMID- 15494339
TI  - Femoral press-fit fixation of the hamstring tendons for anterior cruciate
      ligament reconstruction.
AB  - BACKGROUND: Press-fit fixation of patellar tendon-bone anterior cruciate ligament
      autografts is an interesting technique because no hardware is necessary. For
      hamstring tendon grafts, no biomechanical data exist of a press-fit procedure.
      HYPOTHESIS: Press-fit femoral fixation of hamstring tendons is mechanically
      equivalent to press-fit patellar tendon-bone fixation. STUDY DESIGN: Controlled
      laboratory study. METHODS: Patellar and hamstring tendons of 30 human cadavers
      (age, 53.8 +/- 18.0 years) were used. An outside-in press-fit fixation with a
      knot in the semitendinosus and gracilis tendons and an inside-out and outside-in
      fixation with the tendons wrapped around a bone block were compared with patellar
      tendon-bone press-fit fixation in 30 ovine femora. Constructs were cyclically
      strained and then loaded until failure. Maximum load to failure, stiffness, and
      elongation during failure testing and cyclical loading were investigated.
      RESULTS: The maximum load to failure was 561 +/- 309 N for the patellar tendon,
      599 +/- 234 N for the semitendinosus/gracilis tendons knot construct, 678 +/- 231
      for the semitendinosus/gracilis tendons bone construct inserted outside in, and
      339 +/- 236 for the semitendinosus/gracilis tendons bone construct inserted
      inside out (inferior to the others; analysis of variance, Dunn test, P < .01).
      Stiffness of the constructs averaged 134 +/- 32 N/mm for the patellar tendon, 124
      +/- 21 N/mm for the knot construct, 118 +/- 27 N/mm for the outside-in fixation,
      and 117 +/- 23 N/mm for inside-out fixation. Elongation during initial cyclical
      loading was 0.7 +/- 0.6 mm for the patellar tendon, 1.6 +/- 0.5 mm for the knot
      construct, 1.9 +/- 1.2 mm for the outside-in fixation, and 1.9 +/- 0.9 mm for the
      inside-out fixation (significantly larger for all semitendinosus/gracilis tendon
      techniques, P < .05). CONCLUSIONS: Failure loads for the semitendinosus/gracilis
      tendons bone construct inserted outside in and the semitendinosus/ gracilis
      tendons knot construct were within the confidence interval of the patellar tendon
      press-fit fixation. All semitendinosus/ gracilis tendon graft techniques
      exhibited larger elongation during initial cyclical loading than the patellar
      tendon graft. There was no difference in stiffness between all techniques.
      CLINICAL RELEVANCE: Two of the 3 hamstring press-fit fixation techniques showed
      loads to failure similar to the patellar tendon fixation. Preconditioning of the
      constructs is critical. These results must be interpreted with care because of
      high standard deviations.

PMID- 15494340
TI  - A new mechanical testing device for measuring anteroposterior knee laxity.
AB  - BACKGROUND: The authors assessed a new instrument, the Rolimeter, for the
      measurement of anteroposterior translation in the knee; it was compared to the KT
      1000 arthrometer. PURPOSE: To determine if the Rolimeter offers a valid method
      for the measurement of anteroposterior translation that is as reproducible and
      reliable as the KT-1000 arthrometer. METHODS: Two of 3 observers examined 16
      normal subjects (32 knees) and 36 patients (72 knees) with ligament ruptures
      twice, using both the Rolimeter and the KT-1000 arthrometers, 30 minutes apart.
      Total anteroposterior translation (manual maximal Lachman test) was recorded at
      20 degrees and 80 degrees of knee flexion. RESULTS: On average, the Rolimeter
      measured approximately 1 mm less anteroposterior displacement than the KT-1000
      arthrometer at manual maximum stress. Rolimeter measurements were more consistent
      than the KT-1000 measurements as measured by our observers. Specificity and
      sensitivity were equivalent between the Rolimeter and the KT-1000 arthrometer.
      CONCLUSIONS: The Rolimeter is as reproducible and reliable as the KT-1000
      arthrometer. It offers a valid method for the measurement of anteroposterior
      translation in the knee. Higher accuracy was obtained at 20 degrees of flexion
      for the KT-1000 arthrometer and at 80 degrees of flexion for the Rolimeter.

PMID- 15494341
TI  - Cannulated screw fixation of Jones fractures: a clinical and biomechanical study.
AB  - BACKGROUND: Traditional nonsurgical treatment of Jones fractures has high rates
      of delayed union, nonunion, and refracture. Internal fixation has become the
      treatment of choice in athletes and active patients. PURPOSE: The purpose of this
      study was (1) to review the short- and long-term clinical results of cannulated
      screw fixation of Jones fractures and (2) to perform a biomechanical evaluation
      of fatigue failure characteristics of several types of screws used in the
      fixation of Jones fractures. STUDY DESIGN: Retrospective case series and in vitro
      biomechanical study. METHODS: Ten male and 5 female patients with Jones fractures
      fixed with cannulated screws ranging from 4 mm to 6.5 mm in diameter were
      evaluated by chart review, review of radiographs, and telephone interview. Mean
      follow-up from surgery to phone survey was 34 months. Screws ranging in size from
      2.7 mm to 7.3 mm, both cannulated and noncannulated, stainless steel and
      titanium, were tested in the laboratory by cyclic loading to 250 N up to a
      maximum of 200,000 cycles. RESULTS: Mean time to healing as shown on radiographs
      and by full activity after surgery were 7.3 and 7.9 weeks, respectively. All
      patients were able to return to their previous levels of activity. Screw fatigue
      data showed that the number of cycles to failure increased with increasing screw
      diameter. For 4-mm screws, mean number of cycles to failure was 4308 for
      cannulated titanium screws, 22,012 for cannulated stainless steel screws, and
      44,523 for noncannulated stainless steel screws. CONCLUSIONS: In our patients,
      cannulated screw fixation of Jones fractures was a procedure that was reliable,
      had low morbidity, and afforded athletes a quick return to activity. CLINICAL
      RELEVANCE: The laboratory study suggests that the largest screw possible should
      be used for surgical fixation of these fractures and that screws less than 4 mm
      in diameter should be used with caution.

PMID- 15494342
TI  - Parecoxib impairs early tendon repair but improves later remodeling.
AB  - BACKGROUND: Cyclooxygenase-2 inhibitors inhibit bone repair. HYPOTHESIS:
      Cyclooxygenase inhibitors might also have a negative effect on early tendon
      repair, although a positive effect on late tendon repair previously has been
      shown. STUDY DESIGN: Controlled laboratory study. METHODS: Achilles tendon
      transection was performed on 80 rats. Sixty rats were given daily intramuscular
      injections of either parecoxib (6.4 mg/kg body weight) or saline for the first 5
      days after surgery and sacrificed either at 8 or 14 days. The remaining 20 rats
      were given intramuscular parecoxib or saline injections from day 6 until
      sacrifice at 14 days. RESULTS: At 8 days, early parecoxib treatment caused a 27%
      decrease in force at failure (P = .007), a 25% decrease in maximum stress (P =
      .01), and a 31% decrease in energy uptake (P = .05). Stiffness and transverse
      area were not significantly affected. At 14 days, early parecoxib treatment
      caused a decrease in stiffness (P = .004). In contrast to early treatment, late
      parecoxib treatment caused a 16% decrease in cross-sectional area (P = .03) and a
      29% increase in maximum stress (P = .04). CONCLUSIONS: During early tendon
      repair, a cyclooxygenase-2 inhibitor had a detrimental effect. During
      remodelling, however, inflammation appears to have a negative influence, and
      cyclooxygenase-2 inhibitors might be of value. CLINICAL RELEVANCE: The results
      suggest that cyclooxygenase-2 inhibitors should be used with care in the early
      period after tendon injury.

PMID- 15494343
TI  - Symptomatic "bucket-handle tear" of the medial patellar plicae in three patients:
      congenital or acquired?

PMID- 15494344
TI  - Kissing cartilage lesions of the knee caused by a bioabsorbable meniscal repair
      device: a case report.

PMID- 15494345
TI  - Distal clavicular stress fracture in a female weight lifter: a case report.

PMID- 15494346
TI  - Catastrophic cervical spine injuries in the collision sport athlete, part 2:
      principles of emergency care.
AB  - Catastrophic cervical spine injuries can lead to devastating consequences for the
      collision athlete. Improved understanding of these injuries can lead to
      identification of risk factors, early diagnosis, and effective on-field
      management. This article is the second in a 2-part series. The first part,
      published in the June 2004 issue, reviewed the current concepts regarding the
      epidemiology, functional anatomy, and diagnostic considerations relevant to
      cervical spine trauma in collision sports. In this article, the principles of on
      field emergency care of the spine-injured athlete are reviewed. The authors
      discuss the need for effective pre-event planning, on-field evaluation and
      management of cervical spine injuries, and the transition of care from the
      playing field to the emergency room. The protocol for equipment removal, when
      necessary, is also reviewed. An organized, rapid approach to the management of
      cervical spine-injured collision athletes can help to optimize the outcomes of
      these catastrophic injuries.

PMID- 15494347
TI  - Evaluation and treatment of posterior cruciate ligament injuries: revisited.
AB  - Current knowledge and treatment of posterior cruciate ligament injuries continue
      to lag behind that of anterior cruciate ligament injuries. This is the result of
      the relative infrequency of posterior cruciate ligament injuries and the lack of
      consensus with respect to its natural history, surgical indications, technique,
      and postoperative rehabilitation. Recent anatomical and biomechanical studies
      have improved our understanding of the posterior cruciate ligament in an attempt
      to reproduce its anatomy and function during reconstruction. The following is a
      comprehensive review on the evaluation and treatment of posterior cruciate
      ligament injuries with special focus on the current surgical techniques.

PMID- 15494348
TI  - Acupuncture as a complementary therapy to the pharmacological treatment of
      osteoarthritis of the knee: randomised controlled trial.
AB  - OBJECTIVES: To analyse the efficacy of acupuncture as a complementary therapy to
      the pharmacological treatment of osteoarthritis of the knee, with respect to pain
      relief, reduction of stiffness, and increased physical function during treatment;
      modifications in the consumption of diclofenac during treatment; and changes in
      the patient's quality of life. DESIGN: Randomised, controlled, single blind
      trial, with blinded evaluation and statistical analysis of results. SETTING: Pain
      management unit in a public primary care centre in southern Spain, over a period
      of two years. PARTICIPANTS: 97 outpatients presenting with osteoarthritis of the
      knee. INTERVENTIONS: Patients were randomly separated into two groups, one
      receiving acupuncture plus diclofenac (n = 48) and the other placebo acupuncture
      plus diclofenac (n = 49). MAIN OUTCOME MEASURES: The clinical variables examined
      included intensity of pain as measured by a visual analogue scale; pain,
      stiffness, and physical function subscales of the Western Ontario and McMaster
      Universities (WOMAC) osteoarthritis index; dosage of diclofenac taken during
      treatment; and the profile of quality of life in the chronically ill (PQLC)
      instrument, evaluated before and after the treatment programme. RESULTS: 88
      patients completed the trial. In the intention to treat analysis, the WOMAC index
      presented a greater reduction in the intervention group than in the control group
      (mean difference 23.9, 95% confidence interval 15.0 to 32.8) The reduction was
      greater in the subscale of functional activity. The same result was observed in
      the pain visual analogue scale, with a reduction of 26.6 (18.5 to 34.8). The PQLC
      results indicate that acupuncture treatment produces significant changes in
      physical capability (P = 0.021) and psychological functioning (P = 0.046). Three
      patients reported bruising after the acupuncture sessions. CONCLUSIONS:
      Acupuncture plus diclofenac is more effective than placebo acupuncture plus
      diclofenac for the symptomatic treatment of osteoarthritis of the knee.

PMID- 15494349
TI  - Topoisomerase II inhibitors, irrespective of their chemical composition,
      ameliorate experimental arthritis.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is an autoimmune disease, characterized by a
      chronic inflammation in the joints. The model of collagen-induced arthritis (CIA)
      has been extensively used to elucidate the pathogenic mechanisms relevant to
      human RA and is widely employed for the evaluation of potential anti-rheumatic
      agents. Etoposide and mitoxantrone are immunosuppressive drugs, both acting by
      inhibiting the topoisomerase II function. We have previously demonstrated an
      ameliorating effect of etoposide in CIA. The aims of this study were (1) to
      assess the optimal ameliorating dose of etoposide and (2) to ascertain that
      topoisomerase II inhibition, irrespective of the chemical composition of the
      drug, affects the course of autoimmunity. METHODS: Male DBA/1 mice were treated
      with 12.5 mg/kg body weight of etoposide five times, twice, once per week or once
      every second week. Mitoxantrone was administered as high dose (1 mg/kg body
      weight five times after immunization or after booster with collagen II) or low
      dose (3 microg/mouse, 5 days/week starting after collagen II immunization or
      after booster). RESULTS: Treatment with 12.5 mg/kg body weight five times or
      twice weekly with etoposide completely inhibited development of arthritis. Low
      dose treatment with mitoxantrone after collagen II immunization or high-dose
      treatment after collagen II booster delayed the onset of arthritis. These results
      were observed clinically as well as histologically. In addition, serum levels of
      anti-collagen II antibodies were significantly lower in mice displaying less
      severe arthritis. CONCLUSION: Treatment of collagen-induced arthritis with
      topoisomerase II inhibitors ameliorates the development of disease.

PMID- 15494350
TI  - Down-regulation of CD40 and CD80 on B cells in patients with life-threatening
      systemic lupus erythematosus after successful treatment with rituximab.
AB  - OBJECTIVES: Systemic lupus erythematosus (SLE) is an autoimmune disease
      characterized by autoreactive T cells and polyclonally activated B cells that
      produce autoantibodies. Five SLE patients who failed to respond to conventional
      immunosuppressants were treated with anti-CD20 antibody (rituximab) and their
      clinical manifestations and laboratory data were evaluated, including phenotypic
      analysis of B cells. METHODS: Rituximab (375 mg/m(2)) was administered weekly for
      2 weeks in five SLE patients who developed severe manifestations despite
      intensive treatment. RESULTS: Rituximab resulted in rapid improvement (within
      several days) in clinical manifestations such as consciousness disorder,
      seizures, progressive sensory disorder, haemolytic crisis, cardiac function and
      laboratory data. The effects lasted 20 months in one patient; other patients were
      in remission for more than 6 months. Flow cytometric analysis revealed down
      regulation of CD40 and CD80 expression on CD19-positive B cells 1 week after
      infusion of rituximab, and such down-regulation was seen for more than 7 months
      in two patients. CONCLUSIONS: Our pilot study provides sufficient evidence of
      excellent tolerability and high efficacy of rituximab therapy in refractory SLE.
      Rituximab not only reduced B-cell number and IgG levels but down-regulated CD40
      and CD80 on B cells, suggesting possible disturbance of T-cell activation through
      these costimulatory molecules. Reduction of both quantity and quality of B cells
      suggests that rituximab could improve the disease course in patients with
      refractory SLE.

PMID- 15494351
TI  - This house believes that low-dose intravenous cyclophosphamide is superior to
      standard high-dose regimes for treatment of lupus nephritis.

PMID- 15494352
TI  - Isolated inflammatory coxitis associated with protrusio acetabuli: a new form of
      juvenile idiopathic arthritis?
AB  - BACKGROUND: Isolated hip disease in the context of chronic childhood inflammatory
      arthritis is uncommon. This paper reports 14 children who presented to the
      rheumatology and orthopaedic departments of our hospitals with severe hip
      symptoms, and who continued to have primarily hip disease throughout their
      clinical course. Our aim was to characterize and present the relevant
      demographic, clinical, investigational, treatment and outcome data from the above
      cohort. METHODS: All paediatric cases with the diagnosis of protrusio acetabuli,
      Otto pelvis or idiopathic chondrolysis who were seen in the past 15 yr at Great
      Ormond Hospital and Middlesex Hospital in London were identified and their case
      notes were searched retrospectively for relevant information. RESULTS: In 11
      cases, the disease progressed to involve no joints other than the contralateral
      hip. None were considered to have a specific subtype of juvenile idiopathic
      arthritis (JIA) and all tested were negative for HLA-B27. Elevation of serum
      inflammatory markers was variable. Protrusio acetabuli was the predominant
      radiological feature. There were definite inflammatory changes on the gadolinium
      enhanced magnetic resonance imaging study in all patients who had this procedure
      performed (seven cases). Microbiological investigations were all consistently
      negative. Severe hip disease resulted in considerable ongoing symptoms and
      disability. Six cases were treated with disease-modifying anti-rheumatic drugs.
      Total hip replacement has been required in four patients to date, with major
      functional improvement. CONCLUSIONS: These cases represent severe and disabling
      primary hip disease with considerable clinical and investigational inflammatory
      features. Such a mode of presentation has not been described previously in the
      context of childhood chronic inflammatory arthritides, and may represent a
      separate oligoarthritis subtype of JIA.

PMID- 15494353
TI  - A step forward for exercise in the management of osteoarthritis.

PMID- 15494354
TI  - Subjective and objective physical limitations in high-functioning renal dialysis
      patients.
AB  - BACKGROUND: The utility of subjective measures of physical function as
      discriminative, evaluative and predictive tools in patients with ESRD is
      accepted, but objective performance tests also provide valuable information on
      patient status. The aims of this study were to determine what objective physical
      limitations exist in a select group of dialysis patients, designated as 'high
      functioning' on the basis that they had low comorbidity and subjectively
      perceived themselves to function well, and to examine relationships between the
      objective and subjective measures. METHODS: Twelve patients (male, 7; female, 5)
      aged 18-55 years, with scores of > or = 75 points in the Short Form-36 Physical
      Function scale (PF) and low comorbidity (Charlson score < or = 2) were recruited
      for comparison with age and sex-matched sedentary controls. Objective performance
      measures included vibration perception threshold (VPT), peak quadriceps
      isokinetic and isometric muscle torque, time to reach peak isometric torque,
      balance (body sway with eyes open and closed), temporal gait parameters and the
      sit to stand test (STST). RESULTS: Dialysis patients demonstrated significant
      deficits by comparison with controls in subjective PF score (P < 0.001), VPT (P <
      0.01), quadriceps isometric and isokinetic torque (P < 0.05, P < 0.005), body
      sway with eyes open (P < 0.01) and closed (P < 0.05), self selected (P < 0.005)
      and maximum (P < 0.01) walk speed, duration of gait cycle (P < 0.05) and STST (P
      < 0.001). There was significant agreement between the subjective PF score and VTP
      (P < 0.01), isokinetic torque (P < 0.05), body sway with eyes open (P < 0.05) and
      closed (P < 0.05), self-selected walk speed (P < 0.01) and STST (P < 0.01).
      CONCLUSIONS: Subtle but significant deficits in subjective and objective physical
      function existed even in this select group of dialysis patients. These findings
      define in more detail the underlying neuromuscular impairments and support the
      early implementation of active targeted rehabilitation programmes. The subjective
      and objective measures used here offer a useful panel of tests for clinical use
      in high-functioning dialysis patients.

PMID- 15494355
TI  - Comparison between somatostatin analogues and ACE inhibitor in the NOD mouse
      model of diabetic kidney disease.
AB  - BACKGROUND: The growth hormone (GH)-insulin-like growth factor (IGF)-SST (SST)
      axis is involved in diabetic nephropathy (DN). We have recently shown a
      beneficial effect on diabetic kidney disease markers by the use of a novel
      somatostatin (SST) analogue (PTR-3173) (S). The purpose of this study is to
      compare the effects of S with a previously used SST analogue (octreotide) and an
      ACE inhibitor (ACEi), a standard of care in DN. METHODS: Non-obese diabetic mice
      (a model of type I diabetes) were treated with either S (DS), octreotide (DO),
      enalapril (DA), or PTR-3173 and enalapril (DAS group) for 3 weeks. RESULTS:
      Diabetic renal hypertrophy was blunted in the DS and DO groups only. Serum GH and
      IGF-I were markedly increased and decreased, respectively, in the D group, a
      change significantly blunted in DO and DS. Diabetic hyperfitration and
      albuminuria were blunted in all the four treated diabetic groups. The marked
      deposition of type IV collagen and PAS material were mildly decreased in DA, but
      more markedly reduced in DS as well as DO. Diabetic renal laminin accumulation
      was suppressed in all treated animal groups. No synergistic effect was observed
      for any parameter in the combination group DAS. CONCLUSION: SST analogues exert
      beneficial effects in most parameters of diabetic kidney disease to the same
      extent as the ACEi. Enalapril treatment had no effect on renal hypertrophy and
      did not cause a significant decrease in mesangial type IV collagen deposition. A
      synergistic effect of combined SST-ACEi therapy could not be shown in this study.

PMID- 15494356
TI  - Proteomics: a novel tool to unravel the patho-physiology of uraemia.
AB  - BACKGROUND: Uraemic toxicity results in the dysfunction of many organ systems,
      provoking an increase in morbidity and mortality. To date, only approximately 90
      uraemic retention solutes have been described. To examine unknown uraemic
      substances thoroughly, the identification of as many compounds as possible in the
      ultrafiltrate and/or plasma of patients would lead to a less biased definition of
      the uraemic retention process compared with what is proposed today. METHODS: We
      describe the application of a novel proteomic tool for the identification of a
      large number of molecules present in ultrafiltrate from uraemic and normal plasma
      obtained with high- or low-flux membranes. Separation by capillary
      electrophoresis was coupled on-line to a mass spectrometer, yielding
      identification of polypeptides based on their molecular weight. RESULTS: Between
      500 and >1000 polypeptides with a molecular weight ranging from 800 to 10,000 Da
      could be detected in individual samples, and were identified via their mass and
      their particular migration time in capillary electrophoresis. In ultrafiltrate
      from uraemic plasma, 1394 polypeptides were detected in the high-flux vs 1046 in
      the low-flux samples, while in ultrafiltrate from normal plasma, 544 polypeptides
      vs 490 were found in ultrafiltrate from normal plasma obtained from membranes
      with comparable cut-off. In addition, polypeptides >5 kDa were virtually only
      detected in the uraemic ultrafiltrate from the high-flux membrane (n = 28 vs n =
      5 with the low-flux membrane). To demonstrate the feasibility of further
      characterizing the detected molecules, polypeptides present exclusively in
      uraemic ultrafiltrate were chosen for sequencing analyses. A 950.6 Da polypeptide
      was identified as a fragment of the salivary proline-rich protein. A 1291.8 Da
      fragment was derived from alpha-fibrinogen. CONCLUSION: The data presented here
      strongly suggest that the application of proteomic approaches such as capillary
      electrophoresis and mass spectrometry will result in the identification of many
      more uraemic solutes than those known at present. This could enable the
      introduction of more direct elimination strategies, since it is possible to
      obtain an extended appreciation of the removal capacities of particular dialyser
      membranes.

PMID- 15494357
TI  - Impaired release of interleukin-6 from human osteoblastic cells in the uraemic
      milieu.
AB  - BACKGROUND: Osteoblast-derived interleukin-6 (IL-6) affects bone metabolism and
      is linked with a number of pathological states characterized by increased bone
      resorption, including osteoporosis and renal osteodystrophy. To examine the
      possibility that uraemia directly influences the release of this cytokine in
      bone, we have investigated the effect of human uraemic serum on the release of IL
      6 from human osteoblast-like cells. METHODS: Individual serum samples collected
      from healthy male volunteers or male haemodialysis patients prior to and during a
      dialysis treatment were assayed for IL-6, interleukin-1beta (IL-1beta) and
      soluble IL-6 receptor (sIL-6R) using specific enzyme-linked immunosorbent assays.
      MG-63 and SaOS-2 cells were cultured in media containing pooled sera from both
      groups and alongside matching charcoal-stripped sera. IL-6 concentrations were
      determined in harvested cell supernatants after 24 h. In further experiments,
      media containing individual sera obtained from five patients at regular intervals
      during their haemodialysis treatment were incubated with MG-63 cells to determine
      the effects of the dialysis process on IL-6 secretion. RESULTS: Haemodialysis
      patients had significantly higher (n = 10, P < 0.001) circulating concentrations
      of IL-6 (7.0 +/- 1.6 pg/ml) than normal subjects (0.4 +/- 0.1 pg/ml), but there
      were no significant differences in the concentrations of either IL-1beta or sIL
      6R. These serum concentrations did not change significantly during 80 min of
      dialysis. IL-6 release by MG-63 cells incubated with charcoal-stripped serum from
      normal or from uraemic subjects was similar. Incubation with untreated sera from
      normal subjects increased IL-6 release by approximately 6-fold above the charcoal
      stripped control, whereas sera from uraemic subjects increased IL-6 release by
      only approximately 2- to 3-fold (normal vs uraemic of 6878 +/- 595 and 2579 +/-
      169 pg/ml, respectively, P < 0.001). Similar results were seen with SaOS-2 cells.
      Haemodialysis did not restore the capacity of uraemic serum to augment IL-6
      release to the same degree as normal serum. CONCLUSIONS: These data show that the
      augmentation of IL-6 release from human osteoblastic cells after incubation with
      normal serum is greater than after uraemic serum. This may indicate the presence
      of an inhibitor of IL-6 release in uraemic serum that is involved in the deranged
      bone turnover of uraemic patients.

PMID- 15494358
TI  - Long-term effects of anti-CD20 monoclonal antibody treatment of cryoglobulinaemic
      glomerulonephritis.
AB  - BACKGROUND: Type II mixed cryoglobulinaemia (MC) is a systemic vasculitis,
      associated in most cases with hepatitis C virus (HCV) infection, and sustained by
      proliferation of oligoclonal cells. Systemic B-cell depletion and clinical
      remission can be achieved in non-Hodgkin lymphoma by a human/mouse chimeric
      monoclonal antibody that specifically reacts with the CD20 antigen (Rituximab).
      Similar effects could be expected in type II MC. METHODS: Six patients, mean age
      64.2 years (range: 37-76 years), with HCV infection genotype 2a2c (three cases)
      or 1b (three cases) and symptomatic type-II MC with systemic manifestations,
      including renal involvement (five cases) and bone marrow clonal restriction
      (three cases), were considered eligible for Rituximab therapy. Rituximab was
      administered intravenously at a dose of 375 mg/m(2) on days 1, 8, 15 and 22. Two
      more doses were administered 1 and 2 months later. No other immunosuppressive
      drugs were added. Response was evaluated by assessing the changes in clinical
      signs, symptoms and laboratory parameters for < or = 18 months. RESULTS: Levels
      of proteinuria, erythrocyte sedimentation rate and cryocrit significantly
      decreased at 2, 6 and 12 months. Rheumatoid factor and IgM significantly
      decreased at 6 months whereas C4 values significantly increased at 2 and 6
      months. HCV viral load and immunoglobulin G remained stable. Bone marrow
      abnormalities were found to reverse to normal in all three positive cases.
      Constitutional symptoms (skin ulcers, purpura, arthralgia, weakness, paraesthesia
      and fever) disappeared or improved. No acute or delayed side effects were
      observed. CONCLUSIONS: Rituximab appears to be a safe and effective therapeutic
      option in symptomatic patients with HCV-associated MC glomerulonephritis and
      signs of systemic vasculitis.

PMID- 15494359
TI  - A linguistic framework for assessing the quality of written patient information:
      its use in assessing methotrexate information for rheumatoid arthritis.
AB  - Patient information leaflets are an important adjunct to verbal exchange between
      doctor and patient. Their value is dependent upon whether they contain useful
      information from the viewpoint of the patient and are easily understood. We
      developed a framework based upon linguistic theory for assessing the quality of
      written patient information and applied it to a set of leaflets about
      methotrexate treatment. Items included the overall structure of the text, the
      technicality of the vocabulary used, the number of content words per clause
      ('lexical density'), and the clarity of the role relationship between author and
      reader. The leaflets consisted of up to nine identifiable sections (range 3-8):
      background information about the drug, summary of its use, dosage instructions,
      outline of benefits and side-effects, monitoring information, constraints on
      patient behavior, storage instructions, and clinical contact availability. Most
      leaflets contained a high number of content words per clause and the identity of
      the author was clear in only three (17%). Linguistic analysis provides highly
      relevant information about written patient information. Together with critical
      assessment of factual and visual aspects, consideration of key linguistic
      features should improve the quality of informational texts for our patients.

PMID- 15494360
TI  - 1800 MHz in vitro exposure device for experimental studies on the effects of
      mobile communication systems.
AB  - A wire patch cell (WPC) operating at the uplink frequency band of GSM 1800 MHz
      has been designed for in vitro experiments with the aim of investigating the
      possible biological effects of electromagnetic radiation associated with cellular
      phones. The 1800 MHz WPC design is a direct descendant of the original 900 MHz
      WPC introduced by Laval et al. This system provides a homogeneous specific
      absorption rate distribution, using four 3.5 cm petri dishes simultaneously.
      Numerical dosimetry has been performed using a commercial code (CST Microwave
      Studio), in order to evaluate accurately the efficiency of the structure (in
      terms of W kg(-1) per 1 W input power) and the distribution in the chosen
      biological target. The numerical results have been confirmed by experimental
      measurements performed by measuring thermal increase due to a high power impulse.
      The efficiency of the structure is 1.25 +/- 25% W kg(-1) per 1 W input power
      higher than the efficiency of the 900 MHz WPC. A few adjustments have been made
      in order to use the WPC in a standard incubator and to avoid thermal increases
      related to the radio frequency exposure. This exposure system has been adopted
      for the experiments scheduled in the RAMP and GUARD projects (VFPE).

PMID- 15494361
TI  - Fluence to effective dose conversion coefficients calculated for monoenergetic
      electrons up to 200 MeV in partial exposure geometries.
AB  - Organ doses and effective doses were calculated for monoenergetic electrons from
      0.1 to 200 MeV using the EGS4 Monte Carlo simulation code and the MIRD-5 human
      phantom in various non-uniform exposure geometries: anterior-posterior (AP) and
      posterior-anterior (PA). Below 1 MeV, the skin is the main contributor to the
      effective dose conversion coefficients for each exposure geometry; however, above
      1 MeV the calculations showed that the effective doses of partial exposures
      depended on the incident electron energy, the place and the size of the exposure
      on the body.

PMID- 15494362
TI  - Measurement of H'(0.07) using the plastic scintillation pulse height weighting
      integration method.
AB  - The pulse height weighting integration method for measuring H'(0.07) using a
      plastic scintillator has been developed through Monte Carlo simulations and
      laboratory tests. In order to design an optimal detector configuration, the
      parameters of input-window thickness and plastic scintillator thickness were
      investigated by EGS4 for their influences on the energy response for electrons.
      Based on the calculated deposited spectra in the plastic scintillator for
      electrons with various incident energies, a weighting function W(E), folded with
      the deposited energy spectra, was introduced in order to obtain a flat energy
      response in the low energy range. A constant response within +/-3% was confirmed,
      by calculation, for electrons with energy >0.15 MeV. In addition, a preliminary
      experiment was performed using three beta sources (90Sr-90Y, 147Pm, 204Tl) and
      the energy response within +/-6% for beta rays with the maximum energy >0.22 MeV
      was obtained. Some factors causing uncertainties in the measurements are also
      discussed in this article.

PMID- 15494363
TI  - Influence of radionuclides distributed in the whole body on the thyroid dose
      estimates obtained from direct thyroid measurements made in Belarus after the
      Chernobyl accident.
AB  - Thyroid dose reconstruction is most accurate when using the results of direct
      thyroid measurements, in which gamma radiation emitted by radionuclides present
      in the thyroid and in the remainder of the body is recorded by means of a
      radiation detector positioned against the neck. A large number of such
      measurements were performed in Belarus in May-June 1986. Owing to the short half
      life of 131I and to the intake and accumulation of caesium radioisotopes (mainly
      134Cs and 137Cs) in the body, the thyroid doses derived from thyroid measurements
      made after the beginning of June 1986 have so far been often considered to be
      unreliable. To evaluate the influence of the caesium radioisotopes to the signal
      recorded by an instrument performing measurement of 131I activity in the thyroid,
      a Monte Carlo method was used to calculate the calibration factors of that
      instrument. These calculations were made for males of six reference ages:
      newborn, 1, 5, 10 and 15 years old, and adult. The calibration factors were
      combined with estimated time-dependent intake functions for 131I and caesium
      radioisotopes. The fractions of the instrument indications that were due to 131I
      in thyroid were thus estimated as a function of the age of the subject that was
      measured and of the time elapsed since the accident. Using this information when
      processing the thyroid measurements made in May 1986 would improve the accuracy
      of the thyroid dose estimates, and may make it possible to use a larger
      proportion of the thyroid measurements made in June 1986.

PMID- 15494364
TI  - Measurement of radioactivity in the soil of Bahawalpur division, Pakistan.
AB  - Bahawalpur is the largest division of the Punjab province in Pakistan. It is
      larger than many countries of the world. Gamma activity from the naturally
      occurring radionuclides namely 226Ra, 232Th, the primordial radionuclide 40K and
      the artificial radionuclide 137Cs was measured in the soil of the Bahawalpur
      division using gamma spectrometry technique. The mean activity of 226Ra, 232Th,
      40K and 137Cs were found to be 32.9 +/- 0.9, 53.6 +/- 1.4, 647.4 +/- 14.1 and 1.5
      +/- 0.2 Bq kg(-1), respectively. The mean radium equivalent activity Raeq,
      external hazard index, internal hazard index and terrestrial absorbed dose rate
      for the area under study are 158.5 +/- 4.1 Bq kg(-1), 0.4, 0.5 and 77.32 nGy h(
      1), respectively. The annual effective dose equivalent to the public was found to
      be 0.5 mSv.

PMID- 15494365
TI  - Human metabolism of radiocaesium revisited.
AB  - Three adult volunteers (2 males and 1 female) have ingested radioactive caesium
      in two edible forms in order to compare the gastrointestinal uptake and the
      subsequent short-term and long-term biokinetics. Foodstuffs made of fresh-water
      fish or mushrooms from regions in Sweden of high 137Cs deposition was ingested
      together with a 134CsCl-solution mixed with soft drinks. Whole-body countings of
      134Cs and 137Cs were performed in the Malmo whole-body counter during a period of
      approximately 50 d prior to, and 200-300 d after the ingestion. Urine and faeces
      were collected the day before and up to 7-10 d after the test meals, and analysed
      for 134Cs and 137Cs. No significant difference in the gastrointestinal uptake
      fraction, f0=0.98, between caesium incorporated into a foodstuff matrix and
      caesium in ionic form was detected. Cumulated faecal excretion during 7 d after
      ingestion accounted for 2-3% of the intake. No significant difference in the long
      term biological half-time was found between caesium present in a food matrix and
      in an aqueous solution in any of the volunteers.

PMID- 15494366
TI  - Variability and heritability of cell division pathways in Toxoplasma gondii.
AB  - A histone 2b-YFP fusion protein stably expressed in Toxoplasma gondii has several
      advantages: it reveals previously hidden details of nuclear morphology; it makes
      it possible to observe cell-cycle events; it provides a basis for quantitative
      measurements of DNA content in living cells; and it enables sorting of live cells
      according to cell-cycle phase or ploidy. With this cell line it was possible to
      recognize and directly clone individual progeny arising from different patterns
      of cell division that produce two, three or four daughter cells. These
      experiments established that the progeny produced by all cell division pathways
      are viable and infective. Furthermore, the number of progeny produced by a mature
      parasite during cell division is not correlated with the number of its siblings.
      The complete repertoire of cell division pathways is therefore inherited by a
      single cell produced through any one of the individual paths. The results expand
      the range of what must be considered normal in T. gondii cell division and
      provide a useful tool for further study of nuclear structure and proliferation in
      this important human pathogen.

PMID- 15494367
TI  - Differential regulation of keratinocyte chemokinesis and chemotaxis through
      distinct nicotinic receptor subtypes.
AB  - Nicotinergic agents can act as both chemokines and chemoattractants for cell
      migration. Epidermal keratinocytes both synthesize acetylcholine and use it as a
      paracrine and autocrine regulator of cell motility. To gain a mechanistic insight
      into nicotinergic control of keratinocyte motility, we determined types of
      nicotinic acetylcholine receptors and signaling pathways regulating keratinocyte
      chemokinesis and chemotaxis, using respective modifications of the agarose gel
      keratinocyte outgrowth assay. Random migration of keratinocytes was significantly
      (P<0.05) inhibited by hemicholinum-3, a metabolic inhibitor of acetylcholine
      synthesis, as well as by the alpha-conotoxins MII and AuIB, preferentially
      blocking alpha3-containing nicotinic acetylcholine receptors. The use of
      antisense oligonucleotides specific for nicotinic-acetylcholine-receptor subunits
      and knockout mice demonstrated pivotal role for the alpha3beta2 channel in
      mediating acetylcholine-dependent chemokinesis. Signaling pathways downstream of
      alpha3beta2 included activation of the protein-kinase-C isoform delta and RhoA
      dependent events. The nicotinergic chemotaxis of keratinocytes was most
      pronounced towards the concentration gradient of choline, a potent agonist of
      alpha7 nicotinic acetylcholine receptor. The alpha7-preferring antagonist alpha
      bungarotoxin significantly (P<0.05) diminished keratinocyte chemotaxis, further
      suggesting a central role for the alpha7 nicotinic acetylcholine receptor. This
      hypothesis was confirmed in experiments with anti-alpha7 antisense
      oligonucleotides and alpha7-knockout mice. The signaling pathway mediating alpha7
      dependent keratinocyte chemotaxis included intracellular calcium, activation of
      calcium/calmodulin-dependent protein-kinase II, conventional isoforms of protein
      kinase C, phosphatidylinositol-3-kinase and engagement of Rac/Cdc42.
      Redistribution of alpha7 immunoreactivity to the leading edge of keratinocytes
      upon exposure to a chemoattractant preceded crescent shape formation and
      directional migration. Application of high-resolution deconvolution microscopy
      demonstrated that, on the cell membrane of keratinocytes, the nicotinic
      acetylcholine receptor subunits localize with the integrin beta1. The obtained
      results demonstrate for the first time that alpha3 and alpha7 nicotinic
      acetylcholine receptors regulate keratinocyte chemokinesis and chemotaxis,
      respectively, and identify signaling pathways mediating these functions, which
      has clinical implications for wound healing and control of cancer metastases.

PMID- 15494368
TI  - Localization of GDP-mannose transporter in the Golgi requires retrieval to the
      endoplasmic reticulum depending on its cytoplasmic tail and coatomer.
AB  - The Saccharomyces cerevisiae GDP-mannose transporter (GMT) encoded by the
      essential gene VRG4/VIG4 is a member of the nucleotide-sugar transporter family
      in the Golgi apparatus. We examined GMT in the secretory mutant cells to
      investigate the mechanism of its localization in the Golgi. At the nonpermissive
      temperature, most GMT was found in the endoplasmic reticulum of sec23ts cells,
      which have defective COPII, and in the vacuole of sec21ts cells, which have
      defective COPI. The C-terminal hydrophilic peptide of GMT that is exposed to the
      cytosol binds to Ret2p, a subunit of the COPI coat. Mutant peptide derivatives
      that have lost a cluster of lysine in the vicinity of the transmembrane domain
      had reduced binding activity to Ret2p and the GMT with this sequence was
      delivered to the vacuole. Our results indicate that GMT escapes from delivery to
      the vacuole by recycling to the endoplasmic reticulum and retrieval requires the
      lysine-rich C-terminal tail that can bind to the COPI coat.

PMID- 15494369
TI  - Aggregation of embryonic stem cells induces Nanog repression and primitive
      endoderm differentiation.
AB  - When embryonic stem cells are allowed to aggregate, the outer layer of the
      aggregated spheres (referred to as embryoid bodies) differentiates into primitive
      endoderm. This initial specification of cell lineage facilitates further
      differentiation of the inner mass of the embryoid bodies. These processes are
      considered to recapitulate early embryonic development from the blastocyst stage
      to the egg-cylinder stage. Formation of the primitive endoderm layer in the
      embryoid bodies was induced solely by aggregation of embryonic stem cells, in the
      presence of leukemia inhibitory factor/STAT3 and serum/BMP4, which were
      considered to be sufficient for embryonic stem cell self-renewal. Interestingly,
      cell aggregation by itself induced Nanog repression at the outer layer, which was
      essential for aggregation-induced primitive endoderm formation. These data
      illustrate aggregation-based cell-fate specification during early embryonic
      development, when downregulation of Nanog plays a crucial role.

PMID- 15494370
TI  - In vivo contribution of murine mesenchymal stem cells into multiple cell-types
      under minimal damage conditions.
AB  - Murine mesenchymal stem cells are capable of differentiating in vitro into
      different lineages under stimulation with certain cytokines, growth factors and
      chemicals. However, the true capacity of these cells to contribute to different
      cell-types in vivo is still unclear, especially under minimal injury conditions.
      In this study, we describe a method of purifying murine mesenchymal stem cells
      from bone marrow and efficiently transducing them using a lentivirus vector
      expressing the eGFP reporter gene. Lentivirus-transduced mesenchymal stem cells
      retained their in vitro ability to differentiate into adipocytes, osteocytes and
      chondrocytes as well as into myocyte- and astrocyte-like cells. eGFP-mesenchymal
      stem cells were delivered systemically into minimally injured syngeneic mice.
      Tracking and tissue-specific differentiation were determined by PCR and
      immunohistochemistry, respectively. We found donor-derived hepatocytes, lung
      epithelial cells, myofibroblasts, myofibers and renal tubular cells in some of
      the recipient mice. Our data indicate that even in the absence of substantial
      injury, phenotypically defined murine mesenchymal stem cells could acquire tissue
      specific morphology and antigen expression and thus contribute to different
      tissue cell-types in vivo.

PMID- 15494371
TI  - Contagious apoptosis facilitated by the HIV-1 envelope: fusion-induced cell-to
      cell transmission of a lethal signal.
AB  - Cells expressing the human immunodeficiency virus (HIV-1) envelope glycoprotein
      complex (Env) can fuse with CD4+ cells. When the apoptotic pathway is initiated
      in Env+ cells ('donor cells'), co-culture with a healthy CD4+ fusion partner
      ('acceptor cells') results in apoptosis of the syncytium and thus is
      'contagious'. The cell-to-cell transmission of the lethal signal was only
      observed when the nuclei from donor cells exhibited pre-apoptotic chromatin
      condensation (PACC), correlating with comet assay-detectable DNA strand breaks,
      which precede caspase activation, as well as the loss of the mitochondrial
      transmembrane potential. Transmission of the lethal signal resulted into
      mitochondrial alterations, and caspase-dependent nuclear pyknosis with
      chromatinolysis affecting both the donor and the acceptor nuclei. In the presence
      of caspase inhibitors, all nuclei of the syncytium formed by fusion of the pre
      apoptotic and the healthy cell manifested PACC, exhibited DNA lesions and lost
      transcriptional activity. Transmission of the lethal signal did not require donor
      cells to contain a nucleus or mitochondrial DNA, yet was inhibited when two
      mitochondrion-stabilizing proteins, Bcl-2 or vMIA, were overexpressed. Contagious
      apoptosis could be induced in primary human T cells, as well as in vivo, in T
      cells exposed to dying Env-expressing cells. Altogether, these data point to a
      novel mechanism through which HIV-1 can induce bystander killing.

PMID- 15494372
TI  - Inhibition of PrPSc formation by lentiviral gene transfer of PrP containing
      dominant negative mutations.
AB  - Currently, there is no treatment to cure transmissible spongiform
      encephalopathies. By taking advantage of the 'prion-resistant' polymorphisms
      Q171R and E219K that naturally exist in sheep and humans, respectively, we have
      evaluated a therapeutic approach of lentiviral gene transfer. Here, we show that
      VSV-G (vesicular stomatitis virus G glycoprotein) pseudotyped FIV-(feline
      immunodeficiency virus) derived vectors carrying the mouse Prnp gene in which
      these mutations have been inserted, are able to inhibit prion replication in
      chronically prion-infected cells. Because lentiviral tools are able to transduce
      post-mitotic cells such as neurons or cells of the lymphoreticular system, this
      result might help the development of gene- or cell-therapy approaches to prion
      disease.

PMID- 15494373
TI  - Nuclear efflux of heterogeneous nuclear ribonucleoprotein C1/C2 in apoptotic
      cells: a novel nuclear export dependent on Rho-associated kinase activation.
AB  - Using a proteomic approach, we searched for protein changes dependent on Rho
      associated kinase (ROCK) during phorbol-12-myristate-13-acetate (PMA)-induced
      apoptosis. We found that heterogeneous nuclear ribonucleoprotein C1 and C2 (hnRNP
      C1/C2), two nuclear restricted pre-mRNA binding proteins, are translocated to the
      cytosolic compartment in a ROCK-dependent manner in PMA-induced pro-apoptotic
      cells, where nuclear envelopes remain intact. The subcellular localization change
      of hnRNP C1/C2 appears to be dependent on ROCK-mediated cytoskeletal change and
      independent of caspase execution and new protein synthesis. Such a ROCK-dependent
      translocation is also seen in TNFalpha-induced apoptotic NIH3T3 cells. By
      overexpressing the dominant active form of ROCK, we showed that a ROCK-mediated
      signal is sufficient to induce translocation of hnRNP C1/C2. Deletion experiments
      indicated that the C-terminal 40-amino-acid region of hnRNP C1/C2 is required for
      ROCK-responsive translocation. By using nuclear yellow fluorescent protein (YFP)
      fusion, we determined that the C-terminal 40-amino-acid region of hnRNP C1/C2 is
      a novel nuclear export signal responsive to ROCK-activation. We conclude that a
      novel nuclear export is activated by the ROCK signaling pathway to exclude hnRNP
      C1/C2 from nucleus, by which the compartmentalization of specific hnRNP
      components is disturbed in apoptotic cells.

PMID- 15494374
TI  - GW182 is critical for the stability of GW bodies expressed during the cell cycle
      and cell proliferation.
AB  - A novel cytoplasmic compartment referred to as GW bodies was initially identified
      using human autoantibodies to a 182 kDa protein named GW182. GW bodies are small,
      generally spherical, cytoplasmic domains that vary in number and size in several
      mammalian cell types examined to date. Based on our earlier studies, GW bodies
      were proposed to be cytoplasmic sites for mRNA storage and/or degradation. In the
      present study, immunogold electron microscopy identified electron dense
      structures of 100-300 nm diameter devoid of a lipid bilayer membrane. These
      structures appeared to comprise clusters of electron dense strands of 8-10 nm in
      diameter. By costaining with CENP-F and PCNA, and employing a double-thymidine
      block to synchronize HeLa cells, GW bodies were observed to be small in early S
      phase and larger during late S and G2 phases of the cell cycle. The majority of
      GW bodies disassembled prior to mitosis and small GW bodies reassembled in early
      G1. The analysis of GW bodies in two experimental models of cell proliferation
      using reversal of 3T3/serum-starvation and concanavalin A stimulation of mouse
      splenocytes and T cells, revealed that proliferating cells contained larger,
      brighter, and more numerous GW bodies as well as up to a fivefold more total
      GW182 protein than quiescent cells. In vitro gene knockdown of GW182 led to the
      disappearance of GW bodies demonstrating that GW182 is a critical component of GW
      bodies. The incremental expression of the GW182 protein in cells induced to
      proliferate and the cyclic formation and breakdown of GW bodies during mitosis
      are intriguing in view of the notion that GW bodies are specialized centers
      involved in maintaining stability and/or controlling degradation of mRNA.

PMID- 15494375
TI  - RXRalpha acts as a carrier for TR3 nuclear export in a 9-cis retinoic acid
      dependent manner in gastric cancer cells.
AB  - Retinoid X receptor (RXR) plays a crucial role in the cross talk between retinoid
      receptors and other hormone receptors including the orphan receptor TR3, forming
      different heterodimers that transduce diverse steroid/thyroid hormone signaling.
      Here we show that RXRalpha exhibits nucleocytoplasmic shuttling in MGC80-3
      gastric cancer cells and that RXRalpha shuttling is energy-dependent through a
      nuclear pore complex (NPC)-mediated pathway for its import and an intact DNA
      binding domain-mediated pathway for its export. In the presence of its ligand 9
      cis retinoic acid, RXRalpha was almost exclusively located in the cytoplasm. More
      importantly, we also show that RXRalpha acts as a carrier to assist translocation
      of TR3, which plays an important role in apoptosis. Both RXRalpha and TR3
      colocalized in the nucleus; however, upon stimulation by 9-cis retinoic acid they
      cotranslocated to the cytoplasm and then localized in the mitochondria. TR3
      export depends on RXRalpha, as in living cells GFP-TR3 alone did not result in
      export from the nucleus even in the presence of 9-cis retinoic acid, whereas GFP
      TR3 cotransfected with RXRalpha was exported out of the nucleus in response to 9
      cis retinoic acid. Moreover, specific reduction of RXRalpha levels caused by anti
      sense RXRalpha abolished TR3 nuclear export. In contrast, specific knockdown of
      TR3 by antisense-TR3 or TR3-siRNA did not affect RXRalpha shuttling. These
      results indicate that RXRalpha is responsible for TR3 nucleocytoplasmic
      translocation, which is facilitated by the RXRalpha ligand 9-cis retinoic acid.
      In addition, mitochondrial TR3, but not RXRalpha, was critical for apoptosis, as
      TR3 mutants that were distributed in the mitochondria induced apoptosis in the
      presence or absence of 9-cis retinoic acid. These data reveal a novel aspect of
      RXRalpha function, in which it acts as a carrier for nucleocytoplasmic
      translocation of orphan receptors.

PMID- 15494376
TI  - Bcr (breakpoint cluster region) protein binds to PDZ-domains of scaffold protein
      PDZK1 and vesicle coat protein Mint3.
AB  - The breakpoint cluster region protein (Bcr) is a large soluble oligomeric
      multidomain protein best known because of its involvement in chronic myelogenous
      leukemia (CML). A chromosomal translocation between its gene and that of the c
      abl kinase ('Philadelphia chromosome') plays a major causative role in that
      malignancy. Thus most attention has been paid to the role of the protein in
      hemopoietic cells. However, Bcr is also expressed in other cell types including
      epithelia. Bcr is generally considered to be a cytoplasmic protein but in
      addition to its kinase and GTPase exchange and activating domains it contains
      potentially membrane-interacting pleckstrin homology and C2 domains as well as a
      PDZ-binding C terminus mediating an interaction with a PDZ-domain protein at
      intercellular junctions of epithelial cells. We have examined the ability of Bcr
      to interact with other epithelial PDZ proteins and found specific binding to both
      the apical PDZK1 protein and the Golgi-localized Mint3. The former is important
      in the organization of several apical functions and the latter in vesicular
      trafficking in the secretory pathway. Hence these findings extend the
      interactions and likely signaling impact of Bcr in epithelia from the cytosol to
      at least these two membrane compartments.

PMID- 15494377
TI  - The rotavirus surface protein VP8 modulates the gate and fence function of tight
      junctions in epithelial cells.
AB  - Rotaviruses constitute a major cause of diarrhea in young mammals. Rotaviruses
      utilize different integrins as cell receptors, therefore upon their arrival to
      the intestinal lumen their integrin receptors will be hidden below the tight
      junction (TJ), on the basolateral membrane. Here we have studied whether the
      rotavirus outer capsid proteins are capable of opening the paracellular space
      sealed by the TJ. From the outermost layer of proteins of the rotavirus, 60
      spikes formed of protein VP4 are projected. VP4 is essential for virus-cell
      interactions and is cleaved by trypsin into peptides VP5 and VP8. Here we found
      that when these peptides are added to confluent epithelial monolayers (Madin
      Darby canine kidney cells), VP8 is capable of diminishing in a dose dependent and
      reversible manner the transepithelial electrical resistance. VP5 exerted no
      effect. VP8 can also inhibit the development of newly formed TJs in a Ca-switch
      assay. Treatment with VP8 augments the paracellular passage of non-ionic tracers,
      allows the diffusion of a fluorescent lipid probe and the apical surface protein
      GP135, from the luminal to the lateral membrane, and triggers the movement of the
      basolateral proteins Na+-K+-ATPase, alphanubeta3 integrin and beta1 integrin
      subunit, to the apical surface. VP8 generates a freeze-fracture pattern of TJs
      characterized by the appearance of loose end filaments, that correlates with an
      altered distribution of several TJ proteins. VP8 given orally to diabetic rats
      allows the enteral administration of insulin, thus indicating that it can be
      employed to modulate epithelial permeability.

PMID- 15494378
TI  - Contribution of JAM-1 to epithelial differentiation and tight-junction biogenesis
      in the mouse preimplantation embryo.
AB  - We have investigated the contribution of the tight junction (TJ) transmembrane
      protein junction-adhesion-molecule 1 (JAM-1) to trophectoderm epithelial
      differentiation in the mouse embryo. JAM-1-encoding mRNA is expressed early from
      the embryonic genome and is detectable as protein from the eight-cell stage.
      Immunofluorescence confocal analysis of staged embryos and synchronized cell
      clusters revealed JAM-1 recruitment to cell contact sites occurred predominantly
      during the first hour after division to the eight-cell stage, earlier than any
      other TJ protein analysed to date in this model and before E-cadherin adhesion
      and cell polarization. During embryo compaction later in the fourth cell cycle,
      JAM-1 localized transiently yet precisely to the apical microvillous pole, where
      protein kinase Czeta (PKCzeta) and PKCdelta are also found, indicating a role in
      cell surface reorganization and polarization. Subsequently, in morulae and
      blastocysts, JAM-1 is distributed ubiquitously at cell contact sites within the
      embryo but is concentrated within the trophectoderm apicolateral junctional
      complex, a pattern resembling that of E-cadherin and nectin-2. However, treatment
      of embryos with anti-JAM-1-neutralizing antibodies indicated that JAM-1 did not
      contribute to global embryo compaction and adhesion but rather regulated the
      timing of blastocoel cavity formation dependent upon establishment of the
      trophectoderm TJ paracellular seal.

PMID- 15494379
TI  - Acute colchicine intoxication during clarithromycin administration.
AB  - OBJECTIVE: To report a case of colchicine intoxication occurring with institution
      of clarithromycin. CASE SUMMARY: A 76-year-old man with familial Mediterranean
      fever (FMF) had received colchicine 1.5 mg daily for 6 years. The patient
      underwent 7 days of clarithromycin, amoxicillin, and omeprazole treatment for
      Helicobacter pylori-associated gastritis. Fever, abdominal pain, and diarrhea
      occurred 3 days after treatment initiation. On day 8, dehydration, pancytopenia,
      metabolic acidosis, and increased lipase level necessitated hospitalization.
      Alopecia was observed 2 weeks later. The patient recovered fully after the
      colchicine dosage was reduced to 0.5 mg/day and rehydration was performed. The
      previous dosage was then reinstituted without adverse reaction. An objective
      causality assessment revealed that the adverse event was probable. DISCUSSION:
      Continuous colchicine administration is used in treatment of microcrystalline
      arthritis, Behcet's disease, and FMF. Colchicine is primarily eliminated through
      biliary excretion. Renal elimination and cytochrome P450 metabolism play a less
      significant role. Colchicine is also a substrate of P-glycoprotein, a transporter
      involved in cellular efflux and elimination of numerous drugs. Three cases of
      intoxication have been reported when colchicine was combined with erythromycin,
      josamycin, or clarithromycin. Macrolides are inhibitors of P-glycoprotein and
      cytochrome P450-dependent enzymes and may decrease colchicine's biliary excretion
      through P-glycoprotein inhibition. CONCLUSIONS: Coadministration of colchicine
      and macrolides may impair colchicine elimination, resulting in excess drug
      exposure and toxicity. To this end, colchicine should be used with extreme
      caution in patients receiving P-glycoprotein inhibitors, particularly if they are
      elderly and/or renally compromised.

PMID- 15494380
TI  - Acute myocardial infarction associated with albuterol.
AB  - OBJECTIVE: To report a case of acute myocardial infarction (AMI) following the
      use of albuterol (salbutamol) in a patient without preexisting coronary artery
      disease and to review the related literature. CASE SUMMARY: An 84-year-old white
      woman with no history of cardiac disease was treated for an exacerbation of
      chronic obstructive pulmonary disease with albuterol 5 mg and ipratropium bromide
      500 microg nebulized with oxygen; the albuterol was given in the same dose every
      2 hours. Her respiratory condition improved, but soon after the sixth dose of
      albuterol, she developed increasing chest tightness. The electrocardiogram (ECG)
      showed ST segment elevation in the chest leads (V(2,3)) and, subsequently, the
      troponin I concentration and creatine kinase rose. Urgent coronary angiography
      showed smooth coronary arteries with no obstructive coronary artery disease or
      thrombosis. Left ventriculography showed anterior hypokinesia consistent with
      anterior myocardial injury. A subsequent echocardiogram also revealed normal left
      ventricular size but anterior, anteroseptal, and apical hypokinesia. An objective
      causality assessment revealed that albuterol had a probable likelihood of causing
      the AMI in this patient. DISCUSSION: A MEDLINE search (1966-February 2004)
      revealed 6 other case reports of AMI associated with albuterol treatment. The
      possible pathogenesis of albuterol-induced myocardial necrosis includes
      activation of cardiac and peripheral beta(2)-adrenoceptors, inducing positive
      chronotropic and inotropic effects and vasodilation with coronary blood flow
      redistribution. Albuterol can also cause hypokalemia and other metabolic and
      electrical changes, including prolonged QT interval. These effects may be
      especially detrimental in patients with hypoxia, hypercapnea, and preexisting
      heart diseases. CONCLUSIONS: Although myocardial injury is a rare complication
      following albuterol therapy, clinicians should use high-dose beta(2)-agonists
      with caution. Close monitoring of ECG and metabolic changes is recommended before
      early repeated high doses are administered.

PMID- 15494381
TI  - Stability of cefepime in icodextrin peritoneal dialysis solution.
AB  - BACKGROUND: Icodextrin is a glucose polymer used as an alternative osmotic agent
      in peritoneal dialysis (PD) solutions. Cefepime may be a suitable antibiotic for
      the treatment of PD-related peritonitis. The stability of cefepime in icodextrin
      PD solution has not been examined. OBJECTIVE: To determine the chemical stability
      of cefepime in icodextrin PD solution over a 7-day period. METHODS: Samples were
      prepared by adding cefepime HCl 1000 mg to commercially available 2.0-L bags of
      icodextrin 7.5% PD solution. Nine bags were prepared and stored in the following
      conditions: 3 under refrigeration (4 degrees C), 3 at room temperature (20
      degrees C), and 3 at body temperature (37 degrees C). Study samples were drawn
      from each bag immediately after preparation and at predetermined intervals over
      the subsequent 7 days. Solutions were visually inspected for precipitation,
      cloudiness, or discoloration at each sampling interval. Total concentration of
      cefepime in dialysate fluid was determined by liquid chromatography-tandem mass
      spectrometry. RESULTS: Under refrigeration, a mean +/- SD of 95.7 +/-4.2% of the
      initial cefepime concentration remained at 168 hours (7 days). At room
      temperature, 92.0 +/- 17.9% remained at 48 hours. At body temperature, 92.2 +/-
      4.7% remained at 4 hours. Beyond these respective time points, <90% of the
      initial cefepime concentrations remained. CONCLUSIONS: Pre-mixed cefepime
      icodextrin PD solutions stored at room temperature were stable for up to 48
      hours. However, it is recommended that these be kept refrigerated whenever
      possible. When refrigerated, cefepime-icodextrin solutions were found to be
      stable for up to 7 days. Solutions stored at body temperature were stable up to 4
      hours, permitting the practice of pre-warming solutions prior to administration.

PMID- 15494382
TI  - Not all sulfa drugs are created equal.

PMID- 15494383
TI  - Trivalent intranasal influenza vaccine, live.
AB  - OBJECTIVE: To review human data on the efficacy, safety, and clinical use of
      trivalent intranasal influenza vaccine, live (TIIVL). DATA SOURCES: A MEDLINE
      search (1966-3rd week of January 2004) using the terms influenza vaccine,
      intranasal administration, and FluMist was conducted. References from pertinent
      articles were also reviewed. STUDY SELECTION AND DATA EXTRACTION: Studies
      conducted in humans and published in English were selected. Double-blind,
      controlled trials evaluating the efficacy and safety of TIIVL were evaluated.
      DATA SYNTHESIS: Administration of TIIVL results in mucosal and humoral immunity
      to influenza. Results of clinical trials in children and adults have demonstrated
      that TIIVL reduces the incidence of influenza. In children, TIIVL was also
      associated with a decrease in febrile illness and febrile otitis media. In
      adults, reductions in workday absences and medical visits due to febrile upper
      respiratory tract illness were also documented. TIIVL is well tolerated, with
      rhinorrhea or nasal congestion and sore throat occurring more frequently than
      with placebo. CONCLUSIONS: TIIVL is an alternative to intramuscular inactivated
      influenza vaccine in healthy individuals between 5 and 49 years of age. However,
      the vaccine is contraindicated in the majority of patient populations for whom
      annual influenza vaccination is recommended.

PMID- 15494384
TI  - Adjunctive granulocyte colony-stimulating factor therapy for diabetic foot
      infections.
AB  - OBJECTIVE: To evaluate the role of granulocyte colony-stimulating factor (G-CSF)
      as adjunctive therapy for the treatment of diabetic foot infections in non
      neutropenic patients. DATA SOURCES: Clinical literature was accessed through
      MEDLINE (1965-April 2004). Key search terms included G-CSF, infection, and
      diabetes. In addition, relevant references from primary and secondary article
      bibliographies were extracted. DATA SYNTHESIS: Three clinical trials evaluating G
      CSF for diabetic foot infections were identified. These data demonstrated
      positive effects of G-CSF on improvement of foot infections and risk of
      amputations. CONCLUSIONS: Controlled trials are necessary to validate the role of
      adjunctive G-CSF at reducing amputations in patients with diabetic foot
      infections.

PMID- 15494385
TI  - Use of erythropoietin in heart failure management.
AB  - OBJECTIVE: To review the use of erythropoietin for anemia in heart failure (HF).
      DATA SOURCES: Peer-reviewed articles in MEDLINE (1966-June 2004) were identified
      and citations from available articles were reviewed using the search terms
      anemia, erythropoietin, and heart failure. DATA SYNTHESIS: Anemia worsens HF
      prognosis. Clinical studies in patients with New York Heart Association Class
      III/IV HF who had hemoglobin <12 mg/dL and were refractory to maximal medical
      management showed that erythropoietin improves symptoms. Larger scale studies
      with mortality endpoints are required to confirm the benefits. CONCLUSIONS: In
      selected patients with severe, chronic HF, erythropoietin may be considered for
      functional improvement. However, routine use of this treatment strategy is not
      recommended until more data are available.

PMID- 15494386
TI  - Fluorouracil-induced neurotoxicity presenting with generalized tonic-clonic
      seizure.

PMID- 15494387
TI  - Probable sulbactam/ampicillin-associated prolonged cholestasis.
AB  - OBJECTIVE: To present a single case of sulbactam/ampicillin-induced chronic
      cholestasis and a literature review of antibiotic-associated chronic cholestasis.
      CASE SUMMARY: A 74-year-old man with Hodgkin's disease in remission developed
      severe and prolonged cholestasis after treatment with sulbactam/ampicillin 750 mg
      twice daily for 7 days. All other etiologies, including Hodgkin's disease, were
      appropriately ruled out and the cholestasis was ascribed to sulbactam/ampicillin
      treatment. The patient improved gradually and became asymptomatic 7 months after
      the last dose of sulbactam/ampicillin. According to the Naranjo probability
      scale, sulbactam/ampicillin was the probable cause of the cholestasis.
      DISCUSSION: Ampicillin, a semisynthetic penicillin, has rarely been associated
      with hepatic injury when used alone. Hepatocellular and acute cholestatic injury
      due to ampicillin have been described. Cholestasis secondary to
      sulbactam/ampicillin use has not been previously reported. CONCLUSIONS:
      Sulbactam/ampicillin, one of the most widely used antibiotics, may cause chronic
      cholestatic hepatitis. Clinicians should be aware of this adverse affect and
      consider it during diagnostic workup of liver injury.

PMID- 15494390
TI  - Mobilization of intracellular copper stores by the ctr2 vacuolar copper
      transporter.
AB  - Copper plays an essential role in processes including signaling to the
      transcription and protein trafficking machinery, oxidative phosphorylation, iron
      mobilization, neuropeptide maturation, and normal development. Whereas much is
      known about intracellular mobilization of ions such as calcium, little
      information is available on how eukaryotic cells mobilize intracellular copper
      stores. We describe a mechanism by which the Saccharomyces cerevisiae Ctr2
      protein provides bioavailable copper via mobilization of intracellular copper
      stores. Whereas Ctr2 exhibits structural similarity to the Ctr1 plasma membrane
      copper importer, microscopic and biochemical fractionation studies localize Ctr2
      to the vacuole membrane. We demonstrate that Ctr2 mobilizes vacuolar copper
      stores in a manner dependent on amino acid residues conserved between the Ctr1
      and Ctr2 copper transport family and that ctr2 Delta mutants hyper-accumulate
      vacuolar copper. Furthermore, a Ctr2 mutant that is mislocalized to the plasma
      membrane stimulates extracellular copper uptake, supporting a direct role for
      Ctr2 in copper transport across membranes. These studies identify a novel
      mechanism for copper mobilization and suggest that organisms cope with copper
      deprivation via the use of intracellular vesicular stores.

PMID- 15494391
TI  - Identification of the transmembrane metal binding site in Cu+-transporting PIB
      type ATPases.
AB  - P(IB)-type ATPases have an essential role maintaining copper homeostasis. Metal
      transport by these membrane proteins requires the presence of a transmembrane
      metal occlusion/binding site. Previous studies showed that Cys residues in the H6
      transmembrane segment are required for metal transport. In this study, the
      participation in metal binding of conserved residues located in transmembrane
      segments H7 and H8 was tested using CopA, a model Cu(+)-ATPase from Archaeoglobus
      fulgidus. Four invariant amino acids in the central portion of H7 (Tyr(682) and
      Asn(683)) and H8 (Met(711) and Ser(715)) were identified as required for Cu(+)
      binding. Replacement of these residues abolished enzyme activity. These proteins
      did not undergo Cu(+)-dependent phosphorylation by ATP but were phosphorylated by
      P(i) in the absence of Cu(+). Moreover, the presence of Cu(+) could not prevent
      the enzyme phosphorylation by P(i). Other conserved residues in the H7-H8 region
      were not required for metal binding. Mutation of two invariant Pro residues had
      little effect on enzyme function. Replacement of residues located close to the
      cytoplasmic end of H7-H8 led to inactive enzymes. However, these were able to
      interact with Cu(+) and undergo phosphorylation. This suggests that the integrity
      of this region is necessary for conformational transitions but not for ligand
      binding. These data support the presence of a unique transmembrane Cu(+)
      binding/translocation site constituted by Tyr-Asn in H7, Met and Ser in H8, and
      two Cys in H6 of Cu(+)-ATPases. The likely Cu(+) coordination during transport
      appears distinct from that observed in Cu(+) chaperone proteins or
      catalytic/redox metal binding sites.

PMID- 15494393
TI  - Contributions of pseudoknots and protein SmpB to the structure and function of
      tmRNA in trans-translation.
AB  - Bacteria contain transfer-messenger RNA (tmRNA), a molecule that during trans
      translation tags incompletely translated proteins with a small peptide to signal
      the proteolytic destruction of defective polypeptides. TmRNA is composed of tRNA-
      and mRNA-like domains connected by several pseudoknots. Using truncated ribosomal
      protein L27 as a reporter for tagging in vitro and in vivo, we have developed
      exceptionally sensitive assays to study the role of Escherichia coli tmRNA in
      trans-translation. Site-directed mutagenesis experiments showed that pseudoknot 2
      and the abutting helix 5 were particularly important for the binding of ribosomal
      protein S1 to tmRNA. Pseudoknot 4 not only facilitated tmRNA maturation but also
      promoted tagging. In addition, the three pseudoknots (pk2 to pk4) were shown to
      play a significant role in the proper folding of the tRNA-like domain. Protein
      SmpB enhanced tmRNA processing, suggesting a new role for SmpB in trans
      translation. Taken together, these results provide unanticipated insights into
      the functions of the pseudoknots and protein SmpB during tmRNA folding,
      maturation, and protein synthesis.

PMID- 15494392
TI  - A role for 14-3-3 tau in E2F1 stabilization and DNA damage-induced apoptosis.
AB  - Genotoxic stress triggers apoptosis through multiple signaling pathways. Recent
      studies have demonstrated a specific induction of E2F1 accumulation and a role
      for E2F1 in apoptosis upon DNA damage. Induction of E2F1 is mediated by
      phosphorylation events that are dependent on DNA damage-responsive protein
      kinases, such as ATM. How ATM phosphorylation leads to E2F1 stabilization is
      unknown. We now show that 14-3-3 tau, a phosphoserine-binding protein, mediates
      E2F1 stabilization. 14-3-3 tau interacts with ATM-phosphorylated E2F1 during DNA
      damage and inhibits E2F1 ubiquitination. Depletion of 14-3-3 tau or E2F1, but not
      E2F2 or E2F3, blocks adriamycin-induced apoptosis. 14-3-3 tau is also required
      for expression and induction of E2F1 apoptotic targets, such as p73, Apaf-1, and
      caspases, during DNA damage. Together, these data demonstrate a novel function
      for 14-3-3 tau in the regulation of E2F1 protein stability and apoptosis during
      DNA damage.

PMID- 15494394
TI  - Dynamic GATA factor interplay at a multicomponent regulatory region of the GATA-2
      locus.
AB  - Given the simplicity of the DNA sequence that mediates binding of GATA
      transcription factors, GATA motifs reside throughout chromosomal DNA. However,
      chromatin immunoprecipitation analysis has revealed that GATA-1 discriminates
      exquisitely among these sites. GATA-2 selectively occupies the -2.8-kilobase (kb)
      region of the GATA-2 locus in the active state despite there being numerous GATA
      motifs throughout the locus. The GATA-1-mediated displacement of GATA-2 is
      tightly coupled to repression of GATA-2 transcription. We have used high
      resolution chromatin immunoprecipitation to show that GATA-1 and GATA-2 occupy
      two additional regions, -3.9 and -1.8 kb of the GATA-2 locus. GATA-1 and GATA-2
      had distinct preferences for occupancy at these regions, with GATA-1 and GATA-2
      occupancy highest at the -3.9- and -1.8-kb regions, respectively. Activation of
      an estrogen receptor fusion to GATA-1 (ER-GATA-1) induced similar kinetics of ER
      GATA-1 occupancy and GATA-2 displacement at the sites. In the transcriptionally
      active state, DNase I hypersensitive sites (HSs) were detected at the -3.9- and 
      1.8-kb regions, with a weak HS at the -2.8-kb region. Whereas ER-GATA-1
      instigated repression abolished the -1.8-kb HS, the -3.9-kb HS persisted in the
      repressed state. Transient transfection analysis provided evidence that the -3.9
      kb region functions distinctly from the -2.8- and -1.8-kb regions. We propose
      that GATA-2 transcription is regulated via the collective actions of complexes
      assembled at the -2.8- and -1.8-kb regions, which share similar properties, and
      through a qualitatively distinct activity of the -3.9-kb complex.

PMID- 15494395
TI  - TDP1 overexpression in human cells counteracts DNA damage mediated by
      topoisomerases I and II.
AB  - Tyrosyl DNA phosphodiesterase 1 (TDP1) is a repair enzyme that removes adducts,
      e.g. of topoisomerase I from the 3'-phosphate of DNA breaks. When expressed in
      human cells as biofluorescent chimera, TDP1 appeared more mobile than
      topoisomerase I, less accumulated in nucleoli, and not chromosome-bound at early
      mitosis. Upon exposure to camptothecin both proteins were cleared from nucleoli
      and rendered less mobile in the nucleoplasm. However, with TDP1 this happened
      much more slowly reflecting most likely the redistribution of nucleolar
      structures upon inhibition of rDNA transcription. Thus, a steady association of
      TDP1 with topoisomerase I seems unlikely, whereas its integration into repair
      complexes assembled subsequently to the stabilization of DNA.topoisomerase I
      intermediates is supported. Cells expressing GFP-tagged TDP1 > 100-fold in excess
      of endogenous TDP1 exhibited a significant reduction of DNA damage induced by the
      topoisomerase I poison camptothecin and could be selected by that drug.
      Surprisingly, DNA damage induced by the topoisomerase II poison VP-16 was also
      diminished to a similar extent, whereas DNA damage independent of topoisomerase I
      or II was not affected. Overexpression of the inactive mutant GFP-TDP1(H263A) at
      similar levels did not reduce DNA damage by camptothecin or VP-16. These
      observations confirm a requirement of active TDP1 for the repair of topoisomerase
      I-mediated DNA damage. Our data also suggest a role of TDP1 in the repair of DNA
      damage mediated by topoisomerase II, which is less clear. Since overexpression of
      TDP1 did not compromise cell proliferation, it could be a pleiotropic resistance
      mechanism in cancer therapy.

PMID- 15494396
TI  - Identification of new genes regulated by the Crt1 transcription factor, an
      effector of the DNA damage checkpoint pathway in Saccharomyces cerevisiae.
AB  - The Crt1 (RFX1) protein in Saccharomyces cerevisiae is an effector of the DNA
      damage checkpoint pathway. It recognizes a 13-bp cis-regulatory element in the 5'
      untranslated region (5'-UTR) of the ribonucleotide reductase genes RNR2, RNR3,
      and RNR4; the HUG1 gene; and itself. We calculated the weight matrix representing
      the Crt1p binding site motif according to analysis of the 5'-UTR sequences of the
      genes that are under its regulation. We subsequently searched the 5'-UTR
      sequences of all the genes in the yeast genome for the occurrence of this motif.
      The motif was found in regulatory regions of 30 genes. A statistical analysis
      showed that it is unlikely that a random gene cluster contains the motif
      conserved as well as the Crt1p binding site. Analysis of microarray data provided
      supporting evidence for five putative Crt1p targets: FSH3, YLR345W, UBC5, NDE2,
      and NTH2. We used reverse transcription-PCR to compare the expression levels of
      these genes in wild-type and crt1Delta strains. Our results indicated that FSH3,
      YLR345W, and NTH2 are indeed under the regulation of Crt1p. Sequence analysis of
      the FSH3p indicated that this protein may be involved in folate metabolism either
      by carrying serine hydrolase activity required for the novel metabolic pathway
      involving dihydrofolate reductase (DHFR) or by directly interacting with the DHFR
      enzyme. We postulate that Crt1p may influence deoxyribonucleotide synthesis not
      only by regulating expression of the RNR genes but also by modulating DHFR
      activity. FSH3p shares significant sequence similarity with the product of the
      human tumor suppressor gene OVCA2. YLR345Wp and NTH2p are enzymes involved in the
      central metabolism under stress conditions.

PMID- 15494397
TI  - SsrA tagging of Escherichia coli SecM at its translation arrest sequence.
AB  - SecM is expressed from the secM-secA operon and activates the expression of secA
      in response to secretion defects. The 3'-end of secM encodes an "arrest
      sequence," which can interact with the ribosomal exit tunnel, preventing complete
      secM translation under secretion-defective conditions. In a cis-acting manner,
      ribosome stalling enhances secA translation. Pro(166) is the last residue
      incorporated when SecM elongation is arrested. We report that secretion
      deficiencies lead to SsrA tagging of SecM after Pro(166), Gly(165), and likely
      Arg(163). Northern blot analysis revealed the presence of a truncated secM
      transcript, likely issued from a secM-secA cleavage. The level of secM
      transcripts was decreased either when secM translation was totally prevented or
      when Pro(166) was mutated. However, the accumulation of a truncated secM
      transcript required secM translation and was prevented when the SecM arrest
      sequence was inactivated by a point mutation changing Pro(166) to Ala. We suggest
      that ribosome pausing at the site encoding the arrest sequence is required for
      formation of the truncated secM mRNA. SsrA tagging affected neither the presence
      of the secM mRNA nor secA expression, even under translocation-defective
      conditions. It is therefore likely that SsrA tagging of SecM occurs only after
      cleavage of secM-secA mRNA within the secM open reading frame encoding the SecM
      arrest sequence. Accumulation of transcripts expressing arrested SecM generated
      growth inhibition that was alleviated by the SsrA tagging system. Therefore, SsrA
      tagging of SecM would rescue ribosomes to avoid excessive jamming of the
      translation apparatus on stop-less secM mRNA.

PMID- 15494399
TI  - Cloning, heterologous expression, and characterization of a phenylalanine
      aminomutase involved in Taxol biosynthesis.
AB  - Biosynthesis of the N-benzoyl phenylisoserinoyl side chain of the anticancer drug
      Taxol starts with the conversion of 2S-alpha-phenylalanine to 3R-beta
      phenylalanine by phenylalanine aminomutase (PAM). A gene cloning approach was
      based on the assumption that PAM would resemble the well known plant enzyme
      phenylalanine ammonia lyase. A phenylalanine ammonia lyase-like sequence acquired
      from a Taxus cuspidata cDNA library was expressed functionally in Escherichia
      coli and confirmed as the target aminomutase that is virtually identical to the
      recombinant enzyme and clone from Taxus chinensis, acquired recently by a reverse
      genetics approach (Bristol-Myers Squibb (August 14, 2003) U. S. Patent WO
      03/066871 A2). The full-length cDNA has an open reading frame of 2094 base pairs
      and encodes a protein of 698 residues with a calculated molecular mass of 76,530
      Da. The recombinant mutase has a pH optimum of 8.5, a k(cat) value of 0.015 s(
      1), and a K(m) of 45 +/- 8 microm for 2S-alpha-phenylalanine. The stereochemical
      mechanism of PAM involves the removal and interchange of the pro-3S hydrogen and
      the amino group, which rebonds at C-3 with retention of configuration. The
      recombinant enzyme appears to catalyze both the forward and reverse reactions
      with specificity for both 2S-alpha-phenylalanine and 3S- or 3R-beta-phenylalanine
      substrates, respectively, whereas the related phenylpropanoids 2S
      aminocyclohexanepropanoic acid, 2R-alpha-phenylalanine, and 2S-alpha-tyrosine are
      not converted to their beta-isomers by the mutase.

PMID- 15494398
TI  - Granzyme M is a regulatory protease that inactivates proteinase inhibitor 9, an
      endogenous inhibitor of granzyme B.
AB  - Granzyme M is a trypsin-fold serine protease that is specifically found in the
      granules of natural killer cells. This enzyme has been implicated recently in the
      induction of target cell death by cytotoxic lymphocytes, but unlike granzymes A
      and B, the molecular mechanism of action of granzyme M is unknown. We have
      characterized the extended substrate specificity of human granzyme M by using
      purified recombinant enzyme, several positional scanning libraries of coumarin
      substrates, and a panel of individual p-nitroanilide and coumarin substrates. In
      contrast to previous studies conducted using thiobenzyl ester substrates (Smyth,
      M. J., O'Connor, M. D., Trapani, J. A., Kershaw, M. H., and Brinkworth, R. I.
      (1996) J. Immunol. 156, 4174-4181), a strong preference for leucine at P1 over
      methionine was demonstrated. The extended substrate specificity was determined to
      be lysine = norleucine at P4, broad at P3, proline > alanine at P2, and leucine >
      norleucine > methionine at P1. The enzyme activity was found to be highly
      dependent on the length and sequence of substrates, indicative of a regulatory
      function for human granzyme M. Finally, the interaction between granzyme M and
      the serpins alpha(1)-antichymotrypsin, alpha(1)-proteinase inhibitor, and
      proteinase inhibitor 9 was characterized by using a candidate-based approach to
      identify potential endogenous inhibitors. Proteinase inhibitor 9 was effectively
      hydrolyzed and inactivated by human granzyme M, raising the possibility that this
      orphan granzyme bypasses proteinase inhibitor 9 inhibition of granzyme B.

PMID- 15494400
TI  - ATP effects on insulin-degrading enzyme are mediated primarily through its
      triphosphate moiety.
AB  - It has been reported previously that ATP inhibits the insulysin reaction
      (Camberos, M. C., Perez, A. A., Udrisar, D. P., Wanderley, M. I., and Cresto, J.
      C. (2001) Exp. Biol. Med. 226, 334-341). We report here that with 2-aminobenzoyl
      GGFLRKHGQ-ethylenediamine-2,4-dinitrophenyl as substrate, ATP and other
      nucleotides increase the rate >20-fold in Tris buffer. There is no specificity
      with respect to the nucleotide; however, ATP is more effective than ADP, which is
      more effective than AMP. Triphosphate itself was as effective as ATP, indicating
      it is this moiety that is responsible for activation. The binding of triphosphate
      was shown to be at a site distinct from the active site, thus acting as a
      noncompetitive activator. With the physiological substrates insulin and amyloid
      beta peptide, nucleotides and triphosphate were without effect. However, with
      small physiological peptides such as bradykinin and dynorphin B-9, ATP and
      triphosphate increased the rate of hydrolysis approximately 10-fold. Triphosphate
      and ATP shifted the oligomeric state of the enzyme from primarily dimer-tetramers
      to a monomer. These data suggest the presence of an allosteric regulatory site on
      insulysin that may shift its specificity toward small peptide substrates.

PMID- 15494401
TI  - Calreticulin promotes folding of functional human leukocyte antigen class I
      molecules in vitro.
AB  - The assembly of MHC class I molecules with beta(2)-microglobulin and peptides is
      assisted by the housekeeping chaperones calnexin, calreticulin, and Erp57 and the
      dedicated accessory protein, tapasin. Tapasin and calreticulin are essential for
      efficient MHC class I assembly, but their precise action during class I assembly
      remains to be elucidated. Previous in vitro studies have demonstrated that the
      lectin calreticulin interacts with monoglucosylated MHC class I heavy chains,
      whatever their state of assembly with light chains and peptide, and inhibits
      their aggregation above physiological temperature. We used a soluble single chain
      HLA-A2/beta(2)-microglobulin molecule, A2SC, to study the effect of calreticulin
      on the peptide binding capacity of HLA class I molecules. Calreticulin inhibited
      the formation of A2SC aggregates both when co-expressed in insect cells and
      during incubations at elevated temperature. Calreticulin dramatically enhanced
      acquisition of peptide binding capacity when added to denatured A2SC molecules
      during refolding at 4 degrees C. However, it had no effect on the rapid loss of
      A2SC peptide binding capacity at physiological temperature. We conclude that
      calreticulin promotes the folding of HLA class I molecules to a state in which,
      at low temperature, they spontaneously acquire peptide binding capacity. However,
      it does not induce or maintain a peptide-receptive state of the class I-binding
      site, which is likely to be promoted by one or several other components of the
      class I loading complexes. By being amenable to complementation with additional
      proteins, the described system should be useful for identification of these
      components.

PMID- 15494402
TI  - Glucagon represses signaling through the mammalian target of rapamycin in rat
      liver by activating AMP-activated protein kinase.
AB  - The opposing actions of glucagon and insulin on glucose metabolism within the
      liver are essential mechanisms for maintaining plasma glucose concentrations
      within narrow limits. Less well studied are the counterregulatory actions of
      glucagon on protein metabolism. In the present study, the effect of glucagon on
      amino acid-induced signaling through the mammalian target of rapamycin (mTOR), an
      important controller of the mRNA binding step in translation initiation, was
      examined using the perfused rat liver as an experimental model. The results show
      that amino acids enhance signaling through mTOR resulting in phosphorylation of
      eukaryotic initiation factor 4E-binding protein (4E-BP)1, the 70-kDa ribosomal
      protein (rp)S6 kinase, S6K1, and rpS6. In contrast, glucagon repressed both basal
      and amino acid-induced signaling through mTOR, as assessed by changes in the
      phosphorylation of 4E-BP1 and S6K1. The repression was associated with the
      activation of protein kinase A and enhanced phosphorylation of LKB1 and the AMP
      activated protein kinase (AMPK). Surprisingly, the phosphorylation of two S6K1
      substrates, rpS6 and eukaryotic initiation factor 4B, was not repressed but
      instead was increased by glucagon treatment, regardless of the amino acid
      concentration. The latter finding could be explained by the glucagon-induced
      phosphorylation of the ERK1 and the 90-kDa rpS6 kinase p90(rsk). Thus, glucagon
      represses phosphorylation of 4E-BP1 and S6K1 through the activation of a protein
      kinase A-LKB-AMPK-mTOR signaling pathway, while simultaneously enhancing
      phosphorylation of other downstream effectors of mTOR through the activation of
      the extracellular signal-regulated protein kinase 1-p90(rsk) signaling pathway.
      Amino acids also enhance AMPK phosphorylation, although to a lesser extent than
      glucagon and amino acids combined.

PMID- 15494403
TI  - Structural dissection of a highly knotted peptide reveals minimal motif with
      antimicrobial activity.
AB  - The increasing occurrence of bacterial resistance to antibiotics is driving a
      renewed interest on antimicrobial peptides, in the hope that understanding the
      structural features responsible for their activity will provide leads into new
      anti-infective drug candidates. Most chemical studies in this field have focused
      on linear peptides of various eukaryotic origins, rather than on structures with
      complex folding patterns found also in nature. We have undertaken the structural
      dissection of a highly knotted, cysteine-rich plant thionin, with the aim of
      defining a minimal, synthetically accessible, structure that preserves the
      bioactive properties of the parent peptide. Using efficient strategies for
      directed disulfide bond formation, we have prepared a substantially simplified
      (45% size reduction) version with undiminished antimicrobial activity against a
      representative panel of pathogens. Analysis by circular dichroism shows that the
      downsized peptide preserves the central double alpha-helix of the parent form as
      an essential bioactive motif. Membrane permeability and surface plasmon resonance
      studies confirm that the mechanism of action remains unchanged.

PMID- 15494404
TI  - Neuroprotective effects of phenylbutyrate in the N171-82Q transgenic mouse model
      of Huntington's disease.
AB  - Huntington's disease (HD) is caused by an expansion of exonic CAG triplet repeats
      in the gene encoding the huntingtin protein (Htt), however, the means by which
      neurodegeneration occurs remains obscure. There is evidence that mutant Htt
      interacts with transcription factors leading to reduced histone acetylation. We
      report that administration of the histone deacetylase inhibitor phenylbutyrate
      after onset of symptoms in a transgenic mouse model of HD significantly extends
      survival and attenuates both gross brain and neuronal atrophy. Administration of
      phenylbutyrate increased brain histone acetylation and decreased histone
      methylation levels as assessed by both immunocytochemistry and Western blots.
      Phenylbutyrate increased mRNA for components of the ubiquitin-proteosomal pathway
      and down-regulated caspases implicated in apoptotic cell death, and active
      caspase 3 immunoreactivity in the striatum. These results show that
      administration of phenylbutyrate, at doses that are well tolerated in man, exerts
      significant neuroprotective effects in a transgenic mouse model of HD, and
      therefore represents a very promising therapeutic approach for HD.

PMID- 15494405
TI  - Hyperphosphorylation and aggregation of tau in experimental autoimmune
      encephalomyelitis.
AB  - Axonal damage is a major morphological correlate and cause of permanent
      neurological deficits in patients with multiple sclerosis (MS), a multifocal,
      inflammatory and demyelinating disease of the central nervous system.
      Hyperphosphorylation and pathological aggregation of microtubule-associated
      protein tau is a common feature of many neurodegenerative diseases with axonal
      degeneration including Alzheimer's disease. We have therefore analyzed tau
      phosphorylation, solubility and distribution in the brainstem of rats with
      experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Tau was
      hyperphosphorylated at several sites also phosphorylated in Alzheimer's disease
      and became partially detergent-insoluble in EAE brains. Morphological examination
      demonstrated accumulation of amorphous deposits of abnormally phosphorylated tau
      in the cell body and axons of neurons within demyelinating plaques.
      Hyperphosphorylation of tau was accompanied by up-regulation of p25, an activator
      of cyclin-dependent kinase 5. Phosphorylation of tau, activation of cdk5, and
      axonal pathology were significantly reduced when diseased rats were treated with
      prednisolone, a standard therapy of acute relapses in MS. Hyperphosphorylation of
      tau was not observed in a genetic or nutritional model of axonal degeneration or
      demyelination, suggesting that inflammation as detected in the brains of rats
      with EAE is the specific trigger of tau pathology. In summary, our data provide
      evidence that axonal damage in EAE and possibly MS is linked to tau pathology.

PMID- 15494406
TI  - Direct measurement of the thermodynamic parameters of amyloid formation by
      isothermal titration calorimetry.
AB  - Amyloid fibril deposition is associated with over 20 degenerative diseases,
      including Alzheimer's, Parkinson's, and prion diseases. Although research over
      the last few years has revealed the morphology and structural features of the
      amyloid form, knowledge about the thermodynamics of amyloid formation is limited.
      Here, we report for the first time a direct thermodynamic study of amyloid
      formation using isothermal titration calorimetry. Beta(2)-microglobulin, a
      protein responsible for dialysis-related amyloidosis, was used for extending
      amyloid fibrils in a seed-controlled reaction in the cell of the calorimeter. We
      investigated the enthalpy and heat capacity changes of the reaction, where the
      monomeric, acid-denatured molecules adopt an ordered, cross-beta-sheet structure
      in the rigid amyloid fibrils. Despite the dramatic difference in morphology,
      beta(2)-microglobulin exhibited a similar heat capacity change upon amyloid
      formation to that of the folding to the native globular state, whereas the
      enthalpy change of the reaction proved to be markedly lower. In comparison with
      the native state, the results outline the important structural features of the
      amyloid fibrils: a similar extent of surface burial even with the supramolecular
      architecture of amyloid fibrils, a lower level of internal packing, and the
      possible presence of unfavorable side chain contributions.

PMID- 15494407
TI  - The malate-aspartate NADH shuttle member Aralar1 determines glucose metabolic
      fate, mitochondrial activity, and insulin secretion in beta cells.
AB  - The NADH shuttle system, which transports reducing equivalents from the cytosol
      to the mitochondria, is essential for the coupling of glucose metabolism to
      insulin secretion in pancreatic beta cells. Aralar1 and citrin are two isoforms
      of the mitochondrial aspartate/glutamate carrier, one key constituent of the
      malate-aspartate NADH shuttle. Here, the effects of Aralar1 overexpression in INS
      1E beta cells and isolated rat islets were investigated for the first time. We
      prepared a recombinant adenovirus encoding for human Aralar1 (AdCA-Aralar1),
      tagged with the small FLAG epitope. Transduction of INS-1E cells and isolated rat
      islets with AdCA-Aralar1 increased aralar1 protein levels and immunostaining
      revealed mitochondrial localization. Compared with control INS-1E cells,
      overexpression of Aralar1 potentiated metabolism secretion coupling stimulated by
      15 mm glucose. In particular, there was an increase of NAD(P)H generation, of
      mitochondrial membrane hyperpolarization, ATP levels, glucose oxidation, and
      insulin secretion (+45%, p < 0.01). Remarkably, this was accompanied by reduced
      lactate production. Rat islets overexpressing Aralar1 secreted more insulin at
      16.7 mm glucose (+65%, p < 0.05) compared with controls. These results show that
      aspartate-glutamate carrier capacity limits glucose-stimulated insulin secretion
      and that Aralar1 overexpression enhances mitochondrial metabolism.

PMID- 15494408
TI  - Calbindin independence of calcium transport in developing teeth contradicts the
      calcium ferry dogma.
AB  - Cytosolic calcium-binding proteins termed calbindins are widely regarded as a key
      component of the machinery used to transport calcium safely across cells. Acting
      as mobile buffers, calbindins are thought to ferry calcium in bulk and
      simultaneously protect against its potentially cytotoxic effects. Here, we
      contradict this dogma by showing that teeth and bones were produced normally in
      null mutant mice lacking calbindin(28kDa). Structural analysis of dental enamel,
      the development of which depends critically on active calcium transport, showed
      that mineralization was unaffected in calbindin(28kDa)-null mutants. An unchanged
      rate of calcium transport was verified by measurements of (45)Ca incorporation
      into developing teeth in vivo. In enamel-forming cells, the absence of
      calbindin(28kDa) was not compensated by other cytosolic calcium-binding proteins
      as detectable by (45)Ca overlay, two-dimensional gel, and equilibrium binding
      analyses. Despite a 33% decrease in cytosolic buffer capacity, cytotoxicity was
      not evident in either the null mutant enamel or its formative cells. This is the
      first definitive evidence that calbindins are not required for active calcium
      transport, either as ferries or as facilitative buffers. Moreover, in challenging
      the broader notion of a cytosolic route for calcium, the findings support an
      alternative paradigm involving passage via calcium-tolerant organelles.

PMID- 15494409
TI  - Mixed macromolecular crowding accelerates the oxidative refolding of reduced,
      denatured lysozyme: implications for protein folding in intracellular
      environments.
AB  - The oxidative refolding of reduced, denatured hen egg white lysozyme in the
      presence of a mixed macromolecular crowding agent containing both bovine serum
      albumin (BSA) and polysaccharide has been studied from a physiological point of
      view. When the total concentration of the mixed crowding agent is 100 g/liter, in
      which the weight ratio of BSA to dextran 70 is 1:9, the refolding yield of
      lysozyme after refolding for 4 h under this condition increases 24% compared with
      that in the presence of BSA and 16% compared with dextran 70. A remarkable
      increase in the refolding yield of lysozyme by a mixed crowding agent containing
      BSA and Ficoll 70 is also observed. Further folding kinetics analyses show that
      these two mixed crowding agents accelerate the oxidative refolding of lysozyme
      remarkably, compared with single crowding agents. These results suggest that the
      stabilization effects of mixed macromolecular crowding agents are stronger than
      those of single polysaccharide crowding agents such as dextran 70 and Ficoll 70,
      whereas the excluded volume effects of mixed macromolecular crowding agents are
      weaker than those of single protein crowding agents such as BSA. Both the
      refolding yield and the rate of the oxidative refolding of lysozyme in these two
      mixed crowded solutions with suitable weight ratios are higher than those in
      single crowded solutions, indicating that mixed macromolecular crowding agents
      are more favorable to lysozyme folding and can be used to simulate the
      intracellular environments more accurately than single crowding agents do.

PMID- 15494410
TI  - Hsp70 and Hsp40 chaperones do not modulate retinal phenotype in SCA7 mice.
AB  - Nine neurodegenerative diseases, including spinocerebellar ataxia type 7 (SCA7),
      are caused by the expansion of polyglutamine stretches in the respective disease
      causing proteins. A hallmark of these diseases is the aggregation of expanded
      polyglutamine-containing proteins in nuclear inclusions that also accumulate
      molecular chaperones and components of the ubiquitin-proteasome system.
      Manipulation of HSP70 and HSP40 chaperone levels has been shown to suppress
      aggregates in cellular models, prevent neuronal death in Drosophila, and improve
      to some extent neurological symptoms in mouse models. An important issue in
      mammals is the relative expression levels of toxic and putative rescuing
      proteins. Furthermore, overexpression of both HSP70 and its co-factor HSP40/HDJ2
      has never been investigated in mice. We decided to address this question in a
      SCA7 transgenic mouse model that progressively develops retinopathy, similar to
      SCA7 patients. To co-express HSP70 and HDJ2 with the polyglutamine protein, in
      the same cell type, at comparable levels and with the same time course, we
      generated transgenic mice that express the heat shock proteins specifically in
      rod photoreceptors. While co-expression of HSP70 with its co-factor HDJ2
      efficiently suppressed mutant ataxin-7 aggregation in transfected cells, they did
      not prevent either neuronal toxicity or aggregate formation in SCA7 mice.
      Furthermore, nuclear inclusions in SCA7 mice were composed of a cleaved mutant
      ataxin-7 fragment, whereas they contained the full-length protein in transfected
      cells. We propose that differences in the aggregation process might account for
      the different effects of chaperone overexpression in cellular and animal models
      of polyglutamine diseases.

PMID- 15494411
TI  - Identification of AcnR, a TetR-type repressor of the aconitase gene acn in
      Corynebacterium glutamicum.
AB  - In Corynebacterium glutamicum, the activity of aconitase is 2.5-4-fold higher on
      propionate, citrate, or acetate than on glucose. Here we show that this variation
      is caused by transcriptional regulation. In search for putative regulators, a
      gene (acnR) encoding a TetR-type transcriptional regulator was found to be
      encoded immediately downstream of the aconitase gene (acn) in C. glutamicum.
      Deletion of the acnR gene led to a 5-fold increased acn-mRNA level and a 5-fold
      increased aconitase activity, suggesting that AcnR functions as repressor of acn
      expression. DNA microarray analyses indicated that acn is the primary target gene
      of AcnR in the C. glutamicum genome. Purified AcnR was shown to be a homodimer,
      which binds to the acn promoter in the region from -11 to -28 relative to the
      transcription start. It thus presumably acts by interfering with the binding of
      RNA polymerase. The acn-acnR organization is conserved in all corynebacteria and
      mycobacteria with known genome sequence and a putative AcnR consensus binding
      motif (CAGNACnnncGTACTG) was identified in the corresponding acn upstream
      regions. Mutations within this motif inhibited AcnR binding. Because the
      activities of citrate synthase and isocitrate dehydrogenase were previously
      reported not to be increased during growth on acetate, our data indicate that
      aconitase is a major control point of tricarboxylic acid cycle activity in C.
      glutamicum, and they identify AcnR as the first transcriptional regulator of a
      tricarboxylic acid cycle gene in the Corynebacterianeae.

PMID- 15494412
TI  - Vascular endothelial cell growth factor attenuates actions of transforming growth
      factor-beta in human endothelial cells.
AB  - Because vascular endothelial cell growth factor (VEGF) and transforming growth
      factor-beta (TGF-beta) are both involved in cellular growth and differentiation,
      we examined whether VEGF modifies TGF-beta signaling cascade in human umbilical
      cord vein endothelial cells (HUVEC). Production of plasminogen activator
      inhibitor-1 (PAI-1), which is under the specific control of TGF-beta, was
      strongly enhanced (3.5-fold) by TGF-beta treatment. Remarkably, physiological
      concentration of VEGF (30 nm) profoundly (by 60%) attenuated the TGF-beta
      stimulation of PAI-1 production without an effect on the basal PAI-1 production.
      In HUVECs transiently transfected with an expression construct containing a PAI-1
      promoter fused to luciferase reporter gene, TGF-beta-stimulation of transcription
      of PAI-1 was clearly (by 60%) inhibited by VEGF. TGF-beta phosphorylation of
      Smad2/3, an obligatory step of intracellular TGF-beta signaling, was also
      suppressed by VEGF. VEGF attenuation of TGF-beta action was also demonstrated in
      two other endothelial cell lines. In conclusion, VEGF attenuates TGF-beta action
      in the human endothelial cell, specifically at the level of transcription of PAI
      1 gene and Smad2/3 phosphorylation.

PMID- 15494413
TI  - The GAT domains of clathrin-associated GGA proteins have two ubiquitin binding
      motifs.
AB  - Ubiquitin (Ub) attachment to membrane proteins can serve as a sorting signal for
      lysosomal delivery. Recognition of Ub as a sorting signal can occur at the trans
      Golgi network and is mediated in part by the clathrin-associated Golgi
      localizing, gamma-adaptin ear domain homology, ARF-binding proteins (GGA). GGA
      proteins bind Ub via a three-helix bundle subdomain in their GAT (GGA and target
      of Myb1 protein) domain, which is also present in the Ub binding domain of target
      of Myb1 protein. Ubiquitin binding by yeast Ggas is required to direct sorting of
      ubiquitinated proteins such as general amino acid permease (Gap1) from the trans
      Golgi network to endosomes. Using affinity chromatography and nuclear magnetic
      resonance spectroscopy, we have found that the human GGA3 GAT domain contains two
      Ub binding motifs that bind to the same surface of ubiquitin. These motifs are
      found within different helices within the three-helix GAT subdomain. When
      functionally analyzed in yeast, each motif was sufficient to mediate trans-Golgi
      network to endosomal sorting of Gap1, and mutation of both motifs resulted in
      defective Gap1 sorting without defects in other GGA-dependent processes.

PMID- 15494414
TI  - Oligomeric Hsp33 with enhanced chaperone activity: gel filtration, cross-linking,
      and small angle x-ray scattering (SAXS) analysis.
AB  - Hsp33, an Escherichia coli cytosolic chaperone, is inactive under normal
      conditions but becomes active upon oxidative stress. It was previously shown to
      dimerize upon activation in a concentration- and temperature-dependent manner.
      This dimer was thought to bind to aggregation-prone target proteins, preventing
      their aggregation. In the present study, we report small angle x-ray scattering
      (SAXS), steady state and time-resolved fluorescence, gel filtration, and
      glutaraldehyde cross-linking analysis of full-length Hsp33. Our circular
      dichroism and fluorescence results show that there are significant structural
      changes in oxidized Hsp33 at different temperatures. SAXS, gel filtration, and
      glutaraldehyde cross-linking results indicate, in addition to the dimers, the
      presence of oligomeric species. Oxidation in the presence of physiological salt
      concentration leads to significant increases in the oligomer population. Our
      results further show that under conditions that mimic the crowded milieu of the
      cytosol, oxidized Hsp33 exists predominantly as an oligomeric species.
      Interestingly, chaperone activity studies show that the oligomeric species is
      much more efficient compared with the dimers in preventing aggregation of target
      proteins. Taken together, these results indicate that in the cell, Hsp33
      undergoes conformational and quaternary structural changes leading to the
      formation of oligomeric species in response to oxidative stress. Oligomeric Hsp33
      thus might be physiologically relevant under oxidative stress.

PMID- 15494415
TI  - Aminopeptidase N (CD13) is a molecular target of the cholesterol absorption
      inhibitor ezetimibe in the enterocyte brush border membrane.
AB  - Intestinal cholesterol absorption is an important regulator of serum cholesterol
      levels. Ezetimibe is a specific inhibitor of intestinal cholesterol absorption
      recently introduced into medical practice; its mechanism of action, however, is
      still unknown. Ezetimibe neither influences the release of cholesterol from mixed
      micelles in the gut lumen nor the transfer of cholesterol to the enterocyte brush
      border membrane. With membrane-impermeable Ezetimibe analogues we could
      demonstrate that binding of cholesterol absorption inhibitors to the brush border
      membrane of small intestinal enterocytes from the gut lumen is sufficient for
      inhibition of cholesterol absorption. A 145-kDa integral membrane protein was
      identified as the molecular target for cholesterol absorption inhibitors in the
      enterocyte brush border membrane by photoaffinity labeling with photoreactive
      Ezetimibe analogues (Kramer, W., Glombik, H., Petry, S., Heuer, H., Schafer, H.
      L., Wendler, W., Corsiero, D., Girbig, F., and Weyland, C. (2000) FEBS Lett. 487,
      293-297). The 145-kDa Ezetimibe-binding protein was purified by three different
      methods and sequencing revealed its identity with the membrane-bound ectoenzyme
      aminopeptidase N ((alanyl)aminopeptidase; EC 3.4.11.2; APN; leukemia antigen
      CD13). The enzymatic activity of APN was not influenced by Ezetimibe (analogues).
      The uptake of cholesterol delivered by mixed micelles by confluent CaCo-2 cells
      was partially inhibited by Ezetimibe and nonabsorbable Ezetimibe analogues.
      Preincubation of confluent CaCo-2 cells with Ezetimibe led to a strong decrease
      of fluorescent APN staining with a monoclonal antibody in the plasma membrane.
      Independent on its enzymatic activity, aminopeptidase N is involved in
      endocytotic processes like the uptake of viruses. Our findings suggest that
      binding of Ezetimibe to APN from the lumen of the small intestine blocks
      endocytosis of cholesterol-rich membrane microdomains, thereby limiting
      intestinal cholesterol absorption.

PMID- 15494416
TI  - PRMT7, a new protein arginine methyltransferase that synthesizes symmetric
      dimethylarginine.
AB  - The cDNA for PRMT7, a recently discovered human protein-arginine
      methyltransferase (PRMT), was cloned and expressed in Escherichia coli and
      mammalian cells. Immunopurified PRMT7 actively methylated histones, myelin basic
      protein, a fragment of human fibrillarin (GAR) and spliceosomal protein SmB.
      Amino acid analysis showed that the modifications produced were predominantly
      monomethylarginine and symmetric dimethylarginine (SDMA). Examination of PRMT7
      expressed in E. coli demonstrated that peptides corresponding to sequences
      contained in histone H4, myelin basic protein, and SmD3 were methylated.
      Furthermore, analysis of the methylated proteins showed that symmetric
      dimethylarginine and relatively small amounts of monomethylarginine and
      asymmetric dimethylarginine were produced. SDMA was also formed when a GRG
      tripeptide was methylated by PRMT7, indicating that a GRG motif is by itself
      sufficient for symmetric dimethylation to occur. Symmetric dimethylation is
      reduced dramatically compared with monomethylation as the concentration of the
      substrate is increased. The data demonstrate that PRMT7 (like PRMT5) is a Type II
      methyltransferase capable of producing SDMA modifications in proteins.

PMID- 15494417
TI  - Cardiotonic steroids differentially affect intracellular Na+ and [Na+]i/[K+]i
      independent signaling in C7-MDCK cells.
AB  - Recently, we reported that ouabain kills renal epithelial and vascular
      endothelial cells independently of elevation of the [Na(+)](i)/[K(+)](i) ratio.
      These observations raised the possibility of finding cardiotonic steroids (CTS)
      that inhibit the Na(+),K(+) pump without attenuating cell survival and vice
      versa. To test this hypothesis, we compared CTS action on Na(+),K(+) pump,
      [Na(+)](i) content, and survival of Madin-Darby canine kidney cells. At a
      concentration of 1 microM, ouabain and other tested cardenolides, as well as
      bufadienolides such as bufalin, cinobufagin, cinobufotalin, and telobufotoxin,
      led to approximately 10-fold inhibition of the Na(+),K(+) pump, a 2-3-fold
      decrease in staining with dimethylthiazol-diphenyltetrazolium (MTT), and massive
      death indicated by detachment of approximately 80% of cells and caspase-3
      activation. In contrast, Na(+),K(+) pump inhibition and elevation of [Na(+)](i)
      seen in the presence of 3 microM marinobufagenin (MBG) and marinobufotoxin did
      not affect MTT staining and cell survival. Inhibition of the Na(+),Rb(+) pump in
      K(+)-free medium was not accompanied by a decline of MTT staining and cell
      detachment but increased sensitivity to CTS. In K(+)-free medium, half-maximal
      inhibition of (86)Rb influx was observed in the presence of 0.04 microM ouabain
      and 0.1 microM MBG, whereas half-maximal detachment and decline of MTT staining
      were detected at 0.03 and 0.004 microM of ouabain versus 10 and 3 microM of MBG,
      respectively. Both ouabain binding and ouabain-induced [Na(+)](i),[K(+)](i)
      independent signaling were suppressed in the presence of MBG. Thus, our results
      show that CTS exhibit distinctly different potency in Na(+),K(+) pump inhibition
      and triggering of [Na(+)](i)/[K(+)](i)-independent signaling, including cell
      death.

PMID- 15494418
TI  - Binding of substrate in two conformations to human prothrombinase drives
      consecutive cleavage at two sites in prothrombin.
AB  - Thrombin formation results from cleavage of prothrombin following Arg(271) and
      Arg(320). Both bonds are accessible for cleavage, yet the sequential action of
      prothrombinase on Arg(320) followed by Arg(271) is implied by the intermediate
      observed during prothrombin activation. We have studied the individual cleavage
      reactions catalyzed by prothrombinase by using a series of recombinant
      derivatives: wild type prothrombin (II(WT)) contained both cleavage sites;
      II(Q271) contained a single cleavable site at Arg(320); II(Q320) and II(A320)
      contained a single cleavable site at Arg(271); and II(QQ) was resistant to
      cleavage. Cleavage at Arg(320) in II(Q271) could account for the initial cleavage
      reaction leading to the consumption of either plasma prothrombin or II(WT),
      whereas cleavage at Arg(271) in either II(Q320) or II(A320) was found to be
      approximately 30-fold slower. Equivalent kinetic constants were obtained for
      three of the four possible half-reactions. Slow cleavage at Arg(271) in intact
      prothrombin resulted from an approximately 30-fold reduction in V(max). Thus, the
      observed pathway of bond cleavage by prothrombinase can be explained by the
      kinetic constants for the four possible individual cleavage reactions. II(Q320)
      was a competitive inhibitor of II(Q271) cleavage, and II(QQ) was a competitive
      inhibitor for each reaction with K(i) approximately K(m). The data are
      inconsistent with previous proposals and suggest a model in which substrates for
      each of the four possible half-reactions bind in a mutually exclusive manner and
      with equal affinity to prothrombinase in a cleavage site-independent way. Despite
      equivalent exosite binding interactions between all four possible substrates and
      the enzyme, we propose that ordered bond cleavage results from the constraints
      associated with the binding of substrates in one of two conformations to a single
      form of prothrombinase.

PMID- 15494419
TI  - Site-directed mutagenesis and kinetic studies of the West Nile Virus NS3 protease
      identify key enzyme-substrate interactions.
AB  - The flavivirus West Nile virus (WNV) has spread rapidly throughout the world in
      recent years causing fever, meningitis, encephalitis, and fatalities. Because the
      viral protease NS2B/NS3 is essential for replication, it is attracting attention
      as a potential therapeutic target, although there are currently no antiviral
      inhibitors for any flavivirus. This paper focuses on elucidating interactions
      between a hexapeptide substrate (Ac-KPGLKR-p-nitroanilide) and residues at S1 and
      S2 in the active site of WNV protease by comparing the catalytic activities of
      selected mutant recombinant proteases in vitro. Homology modeling enabled the
      predictions of key mutations in WNV NS3 protease at S1 (V115A/F, D129A/E/N,
      S135A, Y150A/F, S160A, and S163A) and S2 (N152A) that might influence substrate
      recognition and catalytic efficiency. Key conclusions are that the substrate P1
      Arg strongly interacts with S1 residues Asp-129, Tyr-150, and Ser-163 and, to a
      lesser extent, Ser-160, and P2 Lys makes an essential interaction with Asn-152 at
      S2. The inferred substrate-enzyme interactions provide a basis for rational
      protease inhibitor design and optimization. High sequence conservation within
      flavivirus proteases means that this study may also be relevant to design of
      protease inhibitors for other flavivirus proteases.

PMID- 15494420
TI  - Glycogen synthase kinase 3 beta induces caspase-cleaved tau aggregation in situ.
AB  - Tau is a substrate of caspases, and caspase-cleaved tau has been detected in
      Alzheimer's disease brain but not in control brain. Furthermore, in vitro studies
      have revealed that caspase-cleaved tau is more fibrillogenic than full-length
      tau. Considering these previous findings, the purpose of this study was to
      determine how the caspase cleavage of tau affected tau function and aggregation
      in a cell model system. The effects of glycogen synthase kinase 3 beta (GSK3
      beta), a well established tau kinase, on these processes also were examined. Tau
      or tau that had been truncated at Asp-421 to mimic caspase cleavage (Tau-D421)
      was transfected into cells with or without GSK3 beta, and phosphorylation,
      microtubule binding, and tau aggregation were examined. Tau-D421 was not as
      efficiently phosphorylated by GSK3 beta as full-length tau. Tau-D421 efficiently
      bound microtubules, and in contrast to the full-length tau, co-expression with
      GSK3 beta did not result in a reduction in the ability of Tau-D421 to bind
      microtubules. In the absence of GSK3 beta, neither Tau-D421 nor full-length tau
      formed Sarkosyl-insoluble inclusions. However, in the presence of GSK3 beta, Tau
      D421, but not full-length tau, was present in the Sarkosyl-insoluble fraction and
      formed thioflavin-S-positive inclusions in the cell. Nonetheless, co-expression
      of GSK3 beta and Tau-D421 did not result in an enhancement of cell death. These
      data suggest that a combination of phosphorylation events and caspase activation
      contribute to the tau oligomerization process in Alzheimer's disease, with GSK3
      beta-mediated tau phosphorylation preceding caspase cleavage.

PMID- 15494421
TI  - Polyclonal chemoprotection against temozolomide in a large-animal model of drug
      resistance gene therapy.
AB  - Incorporation of drug resistance genes into gene vectors has 2 important roles in
      stem cell gene therapy: increasing the proportion of gene-corrected cells in vivo
      (ie, in vivo selection) and marrow protection to permit higher or more tightly
      spaced doses of chemotherapy in the treatment of malignant diseases. We studied
      in a clinically relevant canine model of gene therapy the P140K mutant of the
      drug resistance gene methylguanine methyltransferase (MGMT), which encodes a DNA
      repair enzyme that confers resistance to the combination of the MGMT inhibitor
      O(6)-benzylguanine (O(6)BG) and nitrosourea drugs such as carmustine and
      methylating agents such as temozolomide. Two dogs received MGMT(P140K)-transduced
      autologous CD34(+)-selected cells. After stable engraftment, gene marking in
      granulocytes was between 3% and 16% in the 2 animals, respectively. Repeated
      administration of O(6)BG and temozolomide resulted in a multilineage increase in
      gene-modified repopulating cells with marking levels of greater than 98% in
      granulocytes. MGMT(P140K) overexpression prevented the substantial
      myelosuppression normally associated with this drug combination. Importantly,
      hematopoiesis remained polyclonal throughout the course of the study.
      Extrahematopoietic toxicity was minimal, and no signs of myelodysplasia or
      leukemia were detected. These large-animal data support the evaluation of
      MGMT(P140K) in conjunction with O(6)BG and temozolomide in clinical trials.

PMID- 15494422
TI  - Treatment of primary Epstein-Barr virus infection in patients with X-linked
      lymphoproliferative disease using B-cell-directed therapy.
AB  - X-linked lymphoproliferative disease (XLP) is a congenital immunodeficiency that
      is characterized by an abnormal immune response to primary Epstein-Barr virus
      (EBV) infection. After EBV exposure, affected patients often develop fulminant
      infectious mononucleosis (FIM), a life-threatening condition marked by the
      uncontrolled expansion and activation of T and B lymphocytes and macrophages. We
      hypothesized that the rapid elimination of B cells immediately following EBV
      exposure might reduce the severity of primary EBV infection in patients with XLP.
      To test this possibility, we administered the anti-CD20 antibody rituximab to 2
      patients who presented with acute infection. Following treatment, both patients
      exhibited a complete resolution of symptoms and no longer demonstrated detectable
      EBV DNA within circulating lymphocytes. Moreover, neither patient has developed
      FIM or lymphoma in more than 2 years of follow-up. These data suggest that the
      pre-emptive use of B-cell-directed therapy may reduce the morbidity and mortality
      of primary EBV infection in XLP-affected individuals.

PMID- 15494423
TI  - Farnesyltransferase inhibitors interact synergistically with the Chk1 inhibitor
      UCN-01 to induce apoptosis in human leukemia cells through interruption of both
      Akt and MEK/ERK pathways and activation of SEK1/JNK.
AB  - Interactions between the Chk1 inhibitor UCN-01 and the farnesyltransferase
      inhibitor L744832 were examined in human leukemia cells. Combined exposure of
      U937 cells to subtoxic concentrations of UCN-01 and L744832 resulted in a
      dramatic increase in mitochondrial dysfunction, apoptosis, and loss of
      clonogenicity. Similar interactions were noted in other leukemia cells (HL-60,
      Raji, Jurkat) and primary acute myeloid leukemia (AML) blasts. Coadministration
      of L744832 blocked UCN-01-mediated phosphorylation of mitogen-activated protein
      kinase kinase/extracellular signal-regulated kinase (MEK/ERK), leading to down
      regulation of phospho-cyclic adenosine monophosphate responsive element-binding
      protein (phospho-CREB) and -p90(RSK) and activation of p34(cdc2) and stress
      activated protein kinase/ERK kinase/c-Jun N-terminal kinase (SEK/JNK). Combined
      treatment also resulted in pronounced reductions in levels of phospho-Akt, 
      glycogen synthase kinase-3 (-GSK-3), -p70(S6K), -mammalian target of rapamycin (
      mTOR), -forkhead transcription factor (-FKHR), -caspase-9, and -Bad. Ectopic
      expression of Bcl-2 or Bcl-xL but not dominant-negative caspase-8 blocked UCN
      01/L744832-mediated mitochondrial dysfunction and apoptosis but did not prevent
      activation of p34(cdc2) and JNK or inactivation of MEK/ERK and Akt. Enforced
      expression of myristoylated Akt but not constitutively active MEK significantly
      attenuated UCN-01/L744832-induced apoptosis. However, dual transfection with Akt
      and MEK resulted in further protection from UCN-01/L744832-mediated lethality.
      Finally, down-regulation of JNK1 by siRNA significantly reduced the lethality of
      the UCN-01/L744832 regimen. Together, these findings suggest that
      farnesyltransferase inhibitors interrupt the cytoprotective Akt and MAPK pathways
      while reciprocally activating SAPK/JNK in leukemia cells exposed to UCN-01 and,
      in so doing, dramatically increase mitochondria-dependent apoptosis.

PMID- 15494424
TI  - High telomerase activity in granulocytes from clonal polycythemia vera and
      essential thrombocythemia.
AB  - Essential thrombocythemia (ET) and polycythemia vera (PV) are chronic
      myeloproliferative disorders that share the involvement of a multipotent
      progenitor cell and dominance of the transformed clone over normal hematopoiesis.
      On the other hand, the heterogeneity of these diseases with respect to clonal
      development from a common progenitor has been well established. To identify
      useful prognostic indicators, we analyzed telomerase activity (TA), a known
      marker of neoplastic proliferation, in granulocytes (PMNs) and mononuclear cells
      (MNCs) from 22 female patients with ET and PV. Clonality status was determined by
      investigation of X chromosome inactivation patterns (XCIPs). We found a
      statistically significant positive correlation between high TA and monoclonal
      pattern of XCIP. Therefore, our data suggest that the use of multiple tumor
      markers may contribute to a better understanding of the deregulated physiology of
      these disorders and provide useful prognostic factors.

PMID- 15494425
TI  - Impaired dendritic-cell homing in vivo in the absence of Wiskott-Aldrich syndrome
      protein.
AB  - Regulated migration and spatial localization of dendritic cells (DCs) are
      critical events during the initiation of physiologic immune responses and
      maintenance of tolerance. Here we have used cells deficient in the Wiskott
      Aldrich syndrome protein (WASp) to demonstrate the importance of dynamic
      remodeling of the actin cytoskeleton for these trafficking processes to occur in
      vitro and in vivo. On fibronectin-coated surfaces, WASp-null immature murine DCs
      exhibited defects both of attachment and detachment, resulting in impaired net
      translocation compared with normal cells. The chemokinetic response to CCL21,
      which is critical for normal lymphatic trafficking, was also abrogated in the
      absence of WASp. In vivo in both fluorescein isothiocyanate (FITC) and oxazolone
      contact hypersensitivity models, WASp-null Langerhans cell (LC) migration was
      compromised, as judged by exit from the skin as well as by homing to the draining
      lymph node (LN). Furthermore, following systemic challenge with
      lipopolysaccharide (LPS) or toxoplasma-derived antigen, WASp-null DCs showed
      incomplete redistribution to T-cell areas in the spleen. Instead, they were
      retained ectopically in the marginal zone. DC trafficking in vivo is therefore
      dependent on a normally regulated actin cytoskeleton, which performs an essential
      function during maintenance of physiologic immunity and when disturbed may
      contribute significantly to the immunopathology of Wiskott-Aldrich Syndrome.

PMID- 15494426
TI  - Platelet depletion by anti-CD41 (alphaIIb) mAb injection early but not late in
      the course of disease protects against Plasmodium berghei pathogenesis by
      altering the levels of pathogenic cytokines.
AB  - Accumulating evidence indicates that platelets play a critical role in the
      pathogenesis of experimental severe malaria (ESM) elicited by infection with
      Plasmodium berghei. Mice injected on day 1 of P berghei infection (early) with
      either anti-CD41 or anti-CD61 monoclonal antibodies (mAbs) exhibited
      significantly (P<.001) increased survival from ESM compared with infection
      controls, indicating that platelets function early in the disease. In contrast,
      groups of mice treated on days 4, 5, and 6 (late) with anti-CD41 mAb exhibited
      similar mortality as controls. Because platelet depletion by anti-CD41 mAb on day
      4 of infection did not protect mice, and platelet adherence occurs on day 6,
      platelet adherence to endothelium is not required to mediate malarial
      pathogenesis. Few platelet microparticles were detected in the blood during the
      course of malaria, but large numbers of erythrocyte vesicles, microparticles, and
      debris were detected. The protective effect of early anti-CD41 mAb treatment was
      independent of the number of platelets, platelet microparticles, erythrocyte
      platelet conjugates, and erythrocyte vesicles. Mice treated early with anti-CD41
      mAb exhibited markedly altered cytokine production on day 4 of P berghei
      infection (increased interleukin 10 [IL-10], IL-1alpha, IL-6, interferon-gamma
      [IFN-gamma], and tumor necrosis factor alpha [TNF-alpha]; decreased IL-2) but no
      decline in coagulation factors compared with rat immunoglobulin G (IgG)-treated
      controls, indicating that platelets regulate the levels of pathogenic cytokines.

PMID- 15494427
TI  - Oncogenic events regulate tissue factor expression in colorectal cancer cells:
      implications for tumor progression and angiogenesis.
AB  - Tissue factor (TF) is the primary cellular initiator of blood coagulation and a
      modulator of angiogenesis and metastasis in cancer. Indeed, systemic
      hypercoagulability in patients with cancer and TF overexpression by cancer cells
      are both closely associated with tumor progression, but their causes have been
      elusive. We now report that in human colorectal cancer cells, TF expression is
      under control of 2 major transforming events driving disease progression
      (activation of K-ras oncogene and inactivation of the p53 tumor suppressor), in a
      manner dependent on MEK/mitogen-activated protein kinase (MAPK) and
      phosphatidylinositol 3'-kinase (PI3K). Furthermore, the levels of cell-associated
      as well as circulating (microvesicle-associated) TF activity are linked to the
      genetic status of cancer cells. Finally, RNA interference experiments suggest
      that TF expression is an important effector of the K-ras-dependent tumorigenic
      and angiogenic phenotype in vivo. Thus, this study establishes a causal link
      between cancer coagulopathy, angiogenesis, and genetic tumor progression.

PMID- 15494428
TI  - Human mesenchymal stem cells modulate allogeneic immune cell responses.
AB  - Mesenchymal stem cells (MSCs) are multipotent cells found in several adult
      tissues. Transplanted allogeneic MSCs can be detected in recipients at extended
      time points, indicating a lack of immune recognition and clearance. As well, a
      role for bone marrow-derived MSCs in reducing the incidence and severity of graft
      versus-host disease (GVHD) during allogeneic transplantation has recently been
      reported; however, the mechanisms remain to be investigated. We examined the
      immunomodulatory functions of human MSCs (hMSCs) by coculturing them with
      purified subpopulations of immune cells and report here that hMSCs altered the
      cytokine secretion profile of dendritic cells (DCs), naive and effector T cells
      (T helper 1 [T(H)1] and T(H)2), and natural killer (NK) cells to induce a more
      anti-inflammatory or tolerant phenotype. Specifically, the hMSCs caused mature
      DCs type 1 (DC1) to decrease tumor necrosis factor alpha (TNF-alpha) secretion
      and mature DC2 to increase interleukin-10 (IL-10) secretion; hMSCs caused T(H)1
      cells to decrease interferon gamma (IFN-gamma) and caused the T(H)2 cells to
      increase secretion of IL-4; hMSCs caused an increase in the proportion of
      regulatory T cells (T(Regs)) present; and hMSCs decreased secretion of IFN-gamma
      from the NK cells. Mechanistically, the hMSCs produced elevated prostaglandin E2
      (PGE(2)) in co-cultures, and inhibitors of PGE(2) production mitigated hMSC
      mediated immune modulation. These data offer insight into the interactions
      between allogeneic MSCs and immune cells and provide mechanisms likely involved
      with the in vivo MSC-mediated induction of tolerance that could be therapeutic
      for reduction of GVHD, rejection, and modulation of inflammation.

PMID- 15494429
TI  - Donor CD4+CD25+ T cells promote engraftment and tolerance following MHC
      mismatched hematopoietic cell transplantation.
AB  - Allogeneic bone marrow transplantation (BMT) is a potentially curative treatment
      for both inherited and acquired diseases of the hematopoietic compartment;
      however, its wider use is limited by the frequent and severe outcome of graft
      versus-host disease (GVHD). Unfortunately, efforts to reduce GVHD by removing
      donor T cells have resulted in poor engraftment and elevated disease recurrence.
      Alternative cell populations capable of supporting allogeneic hematopoietic
      stem/progenitor cell engraftment without inducing GVHD could increase numbers of
      potential recipients while broadening the pool of acceptable donors. Although
      unfractionated CD4(+) T cells have not been shown to be an efficient facilitating
      population, CD4(+)CD25(+) regulatory cells (T-reg's) were examined for their
      capacity to support allogeneic hematopoietic engraftment. In a murine fully major
      histocompatibility complex (MHC)-mismatched BMT model, cotransplantation of donor
      B6 T-reg's into sublethally conditioned BALB/c recipients supported significantly
      greater lineage-committed and multipotential donor progenitors in recipient
      spleens 1 week after transplantation and significantly increased long-term
      multilineage donor chimerism. Donor engraftment occurred without GVHD-related
      weight loss or lethality and was associated with tolerance to donor and host
      antigens by in vitro and in vivo analyses. Donor CD4(+)CD25(+) T cells may
      therefore represent a potential alternative to unfractionated T cells for
      promotion of allogeneic engraftment in clinical hematopoietic cell
      transplantation.

PMID- 15494430
TI  - CVP chemotherapy plus rituximab compared with CVP as first-line treatment for
      advanced follicular lymphoma.
AB  - The combination of cyclophosphamide, vincristine, and prednisone (CVP) is one of
      several standard treatment options for advanced follicular lymphoma. This, like
      similar chemotherapeutic regimens, induces response rates of 60% to 80%, with a
      median response duration of under 2 years. Rituximab, a chimeric monoclonal
      antibody against CD20, is active in follicular lymphoma, both as monotherapy and
      in combination with chemotherapy. Previously untreated patients with stages III
      to IV follicular lymphoma were randomly assigned to receive either 8 cycles of
      CVP plus rituximab (R-CVP; n = 162) or CVP (n = 159). Overall and complete
      response rates were 81% and 41% in the R-CVP arm versus 57% and 10% in the CVP
      arm, respectively (P < .0001). At a median follow-up of 30 months, patients
      treated with R-CVP had a very significantly prolonged time to progression (median
      32 months versus 15 months for CVP; P < .0001). Median time to treatment failure
      was 27 months in patients receiving R-CVP and 7 months in the CVP arm (P <
      .0001). Rituximab did not add significantly to the toxicity of CVP. The addition
      of rituximab to the CVP regimen significantly improves the clinical outcome in
      patients with previously untreated advanced follicular lymphoma, without
      increased toxicity.

PMID- 15494431
TI  - Truncated thioredoxin (Trx80) induces differentiation of human CD14+ monocytes
      into a novel cell type (TAMs) via activation of the MAP kinases p38, ERK, and
      JNK.
AB  - Thioredoxin truncated at its carboxy terminal (Trx80) acts as a cytokine that
      stimulates monocytes and eosinophils. In the present study, Trx80 was shown to
      induce differentiation of human CD14(+) monocytes into a cell type not described
      previously, which we designate as Trx80-activated monocytes (TAMs). TAMs resemble
      immature dendritic cells (iDCs) generated in the presence of granulocyte
      macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4) in that
      both these cell populations exhibit increased proportions of CD1a(+) and mannose
      receptor (MR)(+) cells. However, in contrast to iDCs, TAMs express high
      proportion of CD14 and lower proportion of CD83 and HLA-DR. Functional assays
      revealed that, in comparison to iDCs, TAMs 1) exhibit a higher pinocytic
      capacity; 2) release significantly higher amounts of the proinflammatory
      cytokines tumor necrosis factor-alpha (TNF alpha), IL-1 beta, and IL-6 and of the
      anti-inflammatory cytokine IL-10; and 3) induce a significantly lower
      proliferative response in allogeneic peripheral blood mononuclear cells (PBMCs).
      Indeed, Trx80 appears to be the first endogenous substance shown to have the
      capacity on its own to induce IL-10 production by monocytes. Analysis of the
      mitogen-activated protein (MAP) kinase signaling pathway revealed that Trx80
      induces phosphorylation of p38, extracellular signal-regulated kinase (ERK) and c
      Jun N-terminal kinase (JNK). We propose that Trx80 is an early signal in response
      to danger, and that TAMs may play a major role in triggering innate immune
      responses.

PMID- 15494432
TI  - Involvement of the urokinase-type plasminogen activator receptor in hematopoietic
      stem cell mobilization.
AB  - We investigated the involvement of the urokinase-type plasminogen-activator
      receptor (uPAR) in granulocyte-colony-stimulating factor (G-CSF)-induced
      mobilization of CD34+ hematopoietic stem cells (HSCs) from 16 healthy donors.
      Analysis of peripheral blood mononuclear cells (PBMNCs) showed an increased uPAR
      expression after G-CSF treatment in CD33+ myeloid and CD14+ monocytic cells,
      whereas mobilized CD34+ HSCs remained uPAR negative. G-CSF treatment also induced
      an increase in serum levels of soluble uPAR (suPAR). Cleaved forms of suPAR (c
      suPAR) were released in vitro by PBMNCs and were also detected in the serum of G
      CSF-treated donors. c-suPAR was able to chemoattract CD34+ KG1 leukemia cells and
      CD34+ HSCs, as documented by their in vitro migratory response to a chemotactic
      suPAR-derived peptide (uPAR84-95). uPAR84-95 induced CD34+ KG1 and CD34+ HSC
      migration by activating the high-affinity fMet-Leu-Phe (fMLP) receptor (FPR). In
      addition, uPAR84-95 inhibited CD34+ KG1 and CD34+ HSC in vitro migration toward
      the stromal-derived factor 1 (SDF1), thus suggesting the heterologous
      desensitization of its receptor, CXCR4. Finally, uPAR84-95 treatment
      significantly increased the output of clonogenic progenitors from long-term
      cultures of CD34+ HSCs. Our findings demonstrate that G-CSF-induced upregulation
      of uPAR on circulating CD33+ and CD14+ cells is associated with increased uPAR
      shedding, which leads to the appearance of serum c-suPAR. c-suPAR could
      contribute to the mobilization of HSCs by promoting their FPR-mediated migration
      and by inducing CXCR4 desensitization.

PMID- 15494433
TI  - Induction of T-cell development from human cord blood hematopoietic stem cells by
      Delta-like 1 in vitro.
AB  - The Notch signaling pathway plays a key role at several stages of T-lymphocyte
      differentiation. However, it remained unclear whether signals induced by the
      Notch ligand Delta-like 1 could support full T-cell differentiation from a
      defined source of human hematopoietic stem cells (HSCs) in vitro. Here, we show
      that human cord blood-derived HSCs cultured on Delta-like 1-expressing OP9
      stromal cells undergo efficient T-cell lineage commitment and sustained T-cell
      differentiation. A normal stage-specific program of T-cell development was
      observed, including the generation of CD4 and CD8 alpha beta-T-cell receptor
      (TCR)-bearing cells. Induction of T-cell differentiation was dependent on the
      expression of Delta-like 1 by the OP9 cells. Stimulation of the in vitro
      differentiated T cells by TCR engagement induced the expression of T-cell
      activation markers and costimulatory receptors. These results establish an
      efficient in vitro coculture system for the generation of T cells from human
      HSCs, providing a new avenue for the study of early T-cell differentiation and
      function.

PMID- 15494434
TI  - Dendritic-cell activation by secretory phospholipase A2.
AB  - Dendritic cells (DCs), also referred to as the sentinels of the immune system,
      induce and coordinate important functions of immune surveillance. DCs acquire
      immunity-initiating capacity only after a process of maturation usually induced
      by ligands that bind to members of the tumor necrosis factor (TNF) or toll-like
      receptor families. Secretory phospholipase A2 (sPLA2), which hydrolyzes the sn-2
      ester bond of glycerophospholipids, regulates a variety of cellular functions
      including migration of endothelial cells and neurite outgrowth. In the present
      study we investigated the role of sPLA2 in DC biology. We report that human
      monocyte-derived DC cultures lack sPLA2 activity but respond to exogenous sPLA2.
      sPLA2 alone and in cooperation with TNF-alpha and interleukin 1 beta (IL-1beta)
      induced fatty acid release from DC membranes, which was accompanied by
      upregulation of surface markers and by an increase in the migratory and
      immunostimulatory capacity of the DCs. Our findings indicate that secreted
      enzymes such as sPLA2 can contribute to DC maturation and emphasize the role of
      lipid mediators in the regulation of immune responses. This observation may also
      have implications for DC-based vaccine development.

PMID- 15494435
TI  - RhoH, a hematopoietic-specific Rho GTPase, regulates proliferation, survival,
      migration, and engraftment of hematopoietic progenitor cells.
AB  - Rho guanosine triphosphatases (GT-Pases) are recognized as critical mediators of
      signaling pathways regulating actin assembly, migration, proliferation, and
      survival in hematopoietic cells. Here, we have studied a recently identified
      hematopoietic-specific Rho GTPase, RhoH. Unlike most members of the Rho GTPase
      family, RhoH is GTPase deficient and does not cycle between GTP- and guanosine
      diphosphate (GDP)-bound forms, suggesting that regulation of RhoH expression may
      be critical in its activity. We found that RhoH is expressed in murine
      hematopoietic progenitor cells (HPCs) and fully differentiated myeloid and
      lymphoid lineages. In cytokine-stimulated HPCs, knockdown of RhoH expression via
      RNA interference stimulates proliferation, survival, and stromal cell-derived
      factor-1 alpha (SDF-1 alpha)-induced migration in vitro. Conversely, RhoH
      overexpression in these cells via retrovirus-mediated gene transfer is associated
      with impaired activation of Rac GTPases, reduced proliferation, increased
      apoptosis, and defective actin polymerization and chemotaxis. In vivo, HPCs with
      RhoH overexpression demonstrate defective hematopoietic reconstitution capability
      compared with control vector-transduced cells. Our results suggest that RhoH
      serves as a negative regulator of both growth and actin-based function of HPCs
      possibly via suppression of Rac-mediated signaling.

PMID- 15494436
TI  - Cellular integrins function as entry receptors for human cytomegalovirus via a
      highly conserved disintegrin-like domain.
AB  - Human cytomegalovirus (HCMV) is capable of manifesting disease in nearly every
      organ system in immunocompromised patients. This broad pathogenic tropism
      correlates with the ability of the virus to infect all tested vertebrate cell
      types in vitro, a characteristic that has made receptor identification extremely
      difficult. During virus entry, HCMV induces cellular morphological changes and
      signaling cascades consistent with engagement of cellular integrins; however,
      HCMV structural proteins do not possess the widely used RGD integrin-binding
      motif. We identified an integrin-binding disintegrin-like domain within HCMV
      envelope glycoprotein B, a protein required for virus entry and fusion throughout
      the Herpesviridae. Accepted receptor criteria are met through the use of function
      blocking integrin Abs, beta1 integrin knockout mouse fibroblasts, and
      glycoprotein B disintegrin-like peptides, all of which support a critical role
      for alpha2beta1, alpha6beta1, and alphaVbeta3 integrins as HCMV entry receptors
      and signaling mediators acting during the penetration stage of the entry pathway.
      Strikingly, the glycoprotein B disintegrin-like domain is conserved in many human
      and animal herpesviruses, suggesting that integrins may support entry across this
      medically important virus family.

PMID- 15494437
TI  - Fourier transform ion cyclotron resonance MS reveals the presence of a water
      molecule in an enzyme transition-state analogue complex.
AB  - The structures of several powerful inhibitors of hydrolytic enzymes resemble that
      of the altered substrate in the transition state, except that a hydrogen atom
      replaces one substituent (typically the leaving group). To test the hypothesis
      that a water molecule might be present in the gap resulting from this
      replacement, we examined a transition-state analogue complex formed by
      Escherichia coli cytidine deaminase by Fourier transform ion cyclotron resonance
      MS in electrospray mode. Upon nebularization from aqueous solution under
      conditions (pH 5.6) where the enzyme is active, cytidine deaminase remains
      dimeric in the vapor phase. In the presence of inhibitor, the enzyme's exact mass
      can be used to infer the presence at each active site of zinc, 5-fluoro-3,4
      dihydrouridine, and a single water molecule.

PMID- 15494438
TI  - The integrin alpha-subunit leg extends at a Ca2+-dependent epitope in the
      thigh/genu interface upon activation.
AB  - Two activation-dependent Abs to the integrin alphaL-subunit were used to study
      conformational rearrangement of alphaLbeta2 on the cell surface. Activation
      lowered the concentration of Ca2+ required for maximal expression of each
      epitope. Each Ab requires the Ca2+-binding loop in the integrin genu and nearby
      species-specific residues in the thigh domain. Key thigh residues are shielded
      from Ab in the bent integrin conformation by the alpha-subunit calf-1 domain and
      the nearby bent beta leg, suggesting that extension at the genu is required for
      epitope exposure. Activating stimuli and alpha/beta I-like small molecule
      antagonists demonstrate that exposure of epitopes in the integrin alpha- and beta
      subunit legs is coordinate during integrin activation. A coordinating residue
      donated by the calf-1 domain is as important as Ca2+ for mAb binding. Together
      with inspection of the alphaV structure, this result suggests that the genu/calf
      1 interface is maintained in integrin activation, and that extension occurs by a
      rearrangement at the thigh/genu interface.

PMID- 15494439
TI  - Glutamate and acetylcholine corelease at developing synapses.
AB  - Most neurons release a single fast-acting low-molecular-weight transmitter at
      synapses to activate and open postsynaptic ion channels. We challenge this
      principle with evidence for corelease of the two major excitatory transmitters,
      glutamate and acetylcholine (ACh), from single identified neurons in the
      developing frog tadpole spinal cord. Whole-cell patch electrodes were used to
      record from single spinal neurons. When action potentials and inhibition were
      blocked, spontaneous miniature excitatory postsynaptic currents (mEPSCs) were
      recorded. These were fully blocked only by joint application of glutamate [alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and N-methyl
      D-aspartate receptor (NMDAR)] and nicotinic ACh receptor (nAChR) antagonists.
      Fast nAChR and slow NMDAR mEPSCs were isolated pharmacologically. We then show
      that some mEPSCs have both the fast nAChR rise and slow NMDAR decay and conclude
      that some individual synaptic vesicles corelease glutamate and ACh. Whole-cell
      recordings from pairs of neurons were then used to identify the spinal
      interneurons coreleasing the two excitatory transmitters. One anatomical class of
      interneuron with descending axons was found to excite other spinal neurons by
      activating nAChR, AMPAR, and NMDAR simultaneously at its synapses. Although
      Jonas, Bischofberger, and Sandkuhler [Jonas, P., Bischofberger, J. & Sandkuhler,
      J. (1998) Science 281, 419-424] showed that the inhibitory transmitters GABA and
      glycine can be coreleased at spinal synapses, the Xenopus tadpole provides a case
      where the two main CNS excitatory transmitters are released from single vesicles,
      and where the presynaptic neuron coreleasing two transmitters has been
      identified.

PMID- 15494440
TI  - Probing the instabilities in the dynamics of helical fragments from mouse PrPC.
AB  - The first step in the formation of the protease resistant form (PrPSc) of prion
      proteins involves a conformational transition of the monomeric cellular form of
      PrPC to a more stable aggregation prone state PrPC*. A search of PDBselect and
      Escherichia coli and yeast genomes shows that the exact pattern of charges in
      helix 1 (H1) is rare. Among the 23 fragments in PDBselect with the pattern of
      charges that match H1, 83% are helical. Mapping of the rarely found (in E. coli
      and yeast genomes) hydrophobicity patterns in helix 2 (H2) to known secondary
      structures suggests that the PrPC-->PrPC* transition must be accompanied by
      alterations in conformations in second half of H2. We probe the dynamical
      instability in H1 and in the combined fragments of H2 and helix 3 (H3) from mPrPC
      (H2+H3), with intact disulfide bond, using all atom molecular dynamics (MD)
      simulations totaling 680 ns. In accord with recent experiments, we found that H1
      is helical, whereas the double mutant H1[D147A-R151A] is less stable, implying
      that H1 is stabilized by the (i,i + 4) charged residues. The stability of H1
      suggests that it is unlikely to be involved in the PrPC-->PrPC* transition. MD
      simulations of H2+H3 shows that the second half of H2 (residues 184-194) and
      parts of H3 (residues 200-204 and 215-223) undergo a transition from alpha
      helical conformation to a beta and/or random coil state. Simulations using two
      force fields (optimized potentials for liquid simulations and CHARMM) give
      qualitatively similar results. We use the MD results to propose tentative
      structures for the PrPC* state.

PMID- 15494441
TI  - The timing of eukaryotic evolution: does a relaxed molecular clock reconcile
      proteins and fossils?
AB  - The use of nucleotide and amino acid sequences allows improved understanding of
      the timing of evolutionary events of life on earth. Molecular estimates of
      divergence times are, however, controversial and are generally much more ancient
      than suggested by the fossil record. The limited number of genes and species
      explored and pervasive variations in evolutionary rates are the most likely
      sources of such discrepancies. Here we compared concatenated amino acid sequences
      of 129 proteins from 36 eukaryotes to determine the divergence times of several
      major clades, including animals, fungi, plants, and various protists. Due to
      significant variations in their evolutionary rates, and to handle the uncertainty
      of the fossil record, we used a Bayesian relaxed molecular clock simultaneously
      calibrated by six paleontological constraints. We show that, according to 95%
      credibility intervals, the eukaryotic kingdoms diversified 950-1,259 million
      years ago (Mya), animals diverged from choanoflagellates 761-957 Mya, and the
      debated age of the split between protostomes and deuterostomes occurred 642-761
      Mya. The divergence times appeared to be robust with respect to prior assumptions
      and paleontological calibrations. Interestingly, these relaxed clock time
      estimates are much more recent than those obtained under the assumption of a
      global molecular clock, yet bilaterian diversification appears to be
      approximately 100 million years more ancient than the Cambrian boundary.

PMID- 15494442
TI  - The Rai (Shc C) adaptor protein regulates the neuronal stress response and
      protects against cerebral ischemia.
AB  - Rai (Shc C or N-Shc) is a neuron-specific member of the family of Shc-like
      adaptor proteins. Rai functions in the cytoplasmic propagation of Ret-dependent
      survival signals and regulates, in vivo, the number of sympathetic neurons. We
      report here a function of Rai, i.e., the regulation of the neuronal adaptive
      response to environmental stresses. We demonstrate that (i) primary cultures of
      cortical neurons from Rai-/- mice are more sensitive to apoptosis induced by
      hypoxia or oxidative stress; (ii) in Rai-/- mice, ischemia/reperfusion injury
      induces severe neurological deficits, increased apoptosis and size of the infarct
      area, and significantly higher mortality; and (iii) Rai functions as a stress
      response gene that increases phosphatidylinositol 3-kinase activation and Akt
      phosphorylation after hypoxic or oxidation insults. These data suggest that Rai
      has a functional neuroprotective role in brain injury, with possible implications
      in the treatment of stroke.

PMID- 15494443
TI  - The many faces of Cockayne syndrome.

PMID- 15494444
TI  - Development of hydrocephalus in mice lacking SOCS7.
AB  - SOCS7 is a member of the suppressor of cytokine signaling (SOCS) family of
      proteins (SOCS1-SOCS7 and CIS). SOCS proteins are composed of an N-terminal
      domain of variable length, a central Src homology 2 domain, and a C-terminal SOCS
      box. Biochemical and genetic studies have revealed that SOCS1, SOCS2, SOCS3, and
      CIS play an important role in the termination of cytokine and growth factor
      signaling. However, the biological actions of other SOCS proteins are less well
      defined. To investigate the physiological role of SOCS7, we have used gene
      targeting to generate mice that lack expression of the Socs7 gene. Socs7-/- mice
      were born in expected numbers, were fertile, and did not exhibit defects in
      hematopoiesis or circulating glucose or insulin concentrations. However, Socs7-/-
      mice were 7-10% smaller than their wild-type littermates, and within 15 weeks of
      age approximately 50% of the Socs7-/- mice died as a result of hydrocephalus that
      was characterized by cranial distortion, dilation of the ventricular system,
      reduced thickness of the cerebral cortex, and disorganization of the
      subcommissural organ. In situ hybridization studies revealed prominent expression
      of Socs7 in the brain, suggestive of an important functional role of SOCS7 in
      this organ.

PMID- 15494445
TI  - Metal ion-mediated polymer superquenching for highly sensitive detection of
      kinase and phosphatase activities.
AB  - An assay technology for high-throughput screening of kinase and phosphatase
      activities is introduced. The format is based upon superquenching of fluorescent
      conjugated polymers by dye-labeled kinase/phosphatase peptide substrates. The
      sensor platform is composed of highly fluorescent-conjugated polyelectrolytes
      colocated with the phosphate coordinating metal ion gallium on microspheres.
      Phosphorylated peptide substrates containing a quencher bind specifically to the
      metal ions by means of phosphate groups, resulting in quench of polymer
      fluorescence. The modulation of fluorescence signal is proportional to kinase or
      phosphatase activity and is monitored as a turn-off or turn-on signal,
      respectively. The assay is homogeneous and simple and can be run either as an
      endpoint measurement or in a kinetic mode. The assay meets the sensitivity
      required for high-throughput screening of kinase or phosphatase inhibitors and is
      a valuable tool for drug discovery. A modified version of the assay allows for
      the detection of protein phosphorylation.

PMID- 15494446
TI  - Alzheimer's amyloid peptides mediate hypoxic up-regulation of L-type Ca2+
      channels.
AB  - We examined the effects of chronic hypoxia on recombinant human L-type Ca2+
      channel alpha1C subunits stably expressed in HEK 293 cells, using whole-cell
      patch-clamp recordings. Current density was dramatically increased following 24 h
      exposure to chronic hypoxia (CH), and membrane channel protein levels were
      enhanced. CH also increased the levels of Alzheimer's amyloid beta peptides
      (AbetaPs), determined immunocytochemically. Pharmacological prevention of AbetaP
      production (via exposure to inhibitors of secretase enzymes that are required to
      cleave AbetaP from its precursor protein) prevented hypoxic augmentation of
      currents, as did inhibition of vesicular trafficking with bafilomycin A1. The
      enhancing effect of AbetaPs or CH were abolished following incubation with the
      monoclonal 3D6 antibody, raised against the extracellular N' terminus of AbetaP.
      Immunolocalization and immunoprecipitation studies provided compelling evidence
      that AbetaPs physically associated with the alpha1C subunit, and this association
      was promoted by hypoxia. These data suggest an important role for AbetaPs in
      mediating the increase in Ca2+ channel activity following CH and show that
      AbetaPs act post-transcriptionally to promote alpha1C subunit insertion into
      (and/or retention within) the plasma membrane. Such an action will likely
      contribute to the Ca2+ dyshomeostasis of Alzheimer's disease and may contribute
      to the mechanisms underlying the known increased incidence of this
      neurodegenerative disease following hypoxic episodes.

PMID- 15494447
TI  - Dystrophin- and MLP-deficient mouse hearts: marked differences in morphology and
      function, but similar accumulation of cytoskeletal proteins.
AB  - In humans, cytoskeletal dystrophin and muscle LIM protein (MLP) gene mutations
      can cause dilated cardiomyopathy, yet these mutations may have different effects
      in mice, owing to increased accumulation of other, compensatory cytoskeletal
      proteins. Consequently, we characterized left-ventricular (LV) morphology and
      function in vivo using high-resolution cine-magnetic resonance imaging (MRI) in 2
      to 3-month old dystrophin-deficient (mdx) and MLP-null mice, and their
      respective controls. LV passive stiffness was assessed in isolated, perfused
      hearts, and cytoskeletal protein levels were determined using Western blot
      analyses. In mdx mouse hearts, LV-to-body weight ratio, cavity volume, ejection
      fraction, stroke volume, and cardiac output were normal. However, MLP-null mouse
      hearts had 1.2-fold higher LV-to-body weight ratios (P<0.01), 1.5-fold higher end
      diastolic volumes (P<0.01), and decreased ejection fraction compared with
      controls (25% vs. 66%, respectively, P<0.01), indicating dilated cardiomyopathy
      and heart failure. In both models, isolated, perfused heart end-diastolic
      pressure-volume relationships and passive left-ventricular stiffness were normal.
      Hearts from both models accumulated desmin and beta-tubulin, mdx mouse hearts
      accumulated utrophin and MLP, and MLP-null mouse hearts accumulated dystrophin
      and syncoilin. Although the increase in MLP and utrophin in the mdx mouse heart
      was able to compensate for the loss of dystrophin, accumulation of desmin,
      syncoilin and dystrophin were unable to compensate for the loss of MLP, resulting
      in heart failure.

PMID- 15494448
TI  - The C-terminal alphaO helix of human Ogg1 is essential for 8-oxoguanine DNA
      glycosylase activity: the mitochondrial beta-Ogg1 lacks this domain and does not
      have glycosylase activity.
AB  - The human Ogg1 glycosylase is responsible for repairing 8-oxo-7,8-dihydroguanine
      (8-oxoG) in both nuclear and mitochondrial DNA. Two distinct Ogg1 isoforms are
      present; alpha-Ogg1, which mainly localizes to the nucleus and beta-Ogg1, which
      localizes only to mitochondria. We recently showed that mitochondria from rho(0)
      cells, which lack mitochondrial DNA, have similar 8-oxoG DNA glycosylase activity
      to that of wild-type cells. Here, we show that beta-Ogg1 protein levels are
      approximately 80% reduced in rho(0) cells, suggesting beta-Ogg1 is not
      responsible for 8-oxoG incision in mitochondria. Thus, we characterized the
      biochemical properties of recombinant beta-Ogg1. Surprisingly, recombinant beta
      Ogg1 did not show any significant 8-oxoG DNA glycosylase activity in vitro. Since
      beta-Ogg1 lacks the C-terminal alphaO helix present in alpha-Ogg1, we generated
      mutant proteins with various amino acid substitutions in this domain. Of the
      seven amino acid positions substituted (317-323), we identified Val-317 as a
      novel critical residue for 8-oxoG binding and incision. Our results suggest that
      the alphaO helix is absolutely necessary for 8-oxoG DNA glycosylase activity, and
      thus its absence may explain why beta-Ogg1 does not catalyze 8-oxoG incision in
      vitro. Western blot analysis revealed the presence of significant amounts of
      alpha-Ogg1 in human mitochondria. Together with previous localization studies in
      vivo, this suggests that alpha-Ogg1 protein may provide the 8-oxoG DNA
      glycosylase activity for the repair of these lesions in human mitochondrial DNA.
      beta-Ogg1 may play a novel role in human mitochondria.

PMID- 15494449
TI  - Processing of bistranded abasic DNA clusters in gamma-irradiated human
      hematopoietic cells.
AB  - Clustered DNA damages--two or more lesions on opposing strands and within one or
      two helical turns--are formed in cells by ionizing radiation or radiomimetic
      antitumor drugs. They are hypothesized to be difficult to repair, and thus are
      critical biological damages. Since individual abasic sites can be cytotoxic or
      mutagenic, abasic DNA clusters are likely to have significant cellular impact.
      Using a novel approach for distinguishing abasic clusters that are very closely
      spaced (putrescine cleavage) or less closely spaced (Nfo protein cleavage), we
      measured induction and processing of abasic clusters in 28SC human monocytes that
      were exposed to ionizing radiation. gamma-rays induced approximately 1 double
      strand break: 1.3 putrescine-detected abasic clusters: 0.8 Nfo-detected abasic
      clusters. After irradiation, the 28SC cells rejoined double-strand breaks
      efficiently within 24 h. In contrast, in these cells, the levels of abasic
      clusters decreased very slowly over 14 days to background levels. In vitro repair
      experiments that used 28SC cell extracts further support the idea of slow
      processing of specific, closely spaced abasic clusters. Although some clusters
      were removed by active cellular repair, a substantial number was apparently
      decreased by 'splitting' during DNA replication and subsequent cell division. The
      existence of abasic clusters in 28SC monocytes, several days after irradiation
      suggests that they constitute persistent damages that could lead to mutation or
      cell killing.

PMID- 15494450
TI  - Structural organization of mRNA complexes with major core mRNP protein YB-1.
AB  - YB-1 is a universal major protein of cytoplasmic mRNPs, a member of the family of
      multifunctional cold shock domain proteins (CSD proteins). Depending on its
      amount on mRNA, YB-1 stimulates or inhibits mRNA translation. In this study, we
      have analyzed complexes formed in vitro at various YB-1 to mRNA ratios, including
      those typical for polysomal (translatable) and free (untranslatable) mRNPs. We
      have shown that at mRNA saturation with YB-1, this protein alone is sufficient to
      form mRNPs with the protein/RNA ratio and the sedimentation coefficient typical
      for natural mRNPs. These complexes are dynamic structures in which the protein
      can easily migrate from one mRNA molecule to another. Biochemical studies
      combined with atomic force microscopy and electron microscopy showed that mRNA-YB
      1 complexes with a low YB-1/mRNA ratio typical for polysomal mRNPs are incompact;
      there, YB-1 binds to mRNA as a monomer with its both RNA-binding domains. At a
      high YB-1/mRNA ratio typical for untranslatable mRNPs, mRNA-bound YB-1 forms
      multimeric protein complexes where YB-1 binds to mRNA predominantly with its N
      terminal part. A multimeric YB-1 comprises about twenty monomeric subunits; its
      molecular mass is about 700 kDa, and it packs a 600-700 nt mRNA segment on its
      surface.

PMID- 15494451
TI  - Characterization of dRFX2, a novel RFX family protein in Drosophila.
AB  - A transcriptional regulatory element was identified in the region between URE
      (upstream regulatory element) and DRE (DNA replication-related element) in the
      Drosophila PCNA gene promoter. This element plays an important role in promoter
      activity in living flies. A yeast one-hybrid screening using this element as a
      bait allowed isolation of a cDNA encoding a protein which binds to the element in
      vitro. Nucleotide sequence analyses revealed that the cDNA encodes a novel
      protein containing a characteristic DNA-binding domain conserved among the
      regulatory factor X (RFX) family proteins. We termed this protein Drosophila RFX2
      (dRFX2) and this element dRFX2 site. To investigate the function of dRFX2 in
      vivo, we took the strategy of analyzing the dominant negative effects against the
      endogenous dRFX2. Transgenic flies were established in which expression of HA
      dRFX(202-480) carrying the amino acid sequences from 202 to 480 containing the
      RFX domain (DNA-binding domain) of dRFX2 was targeted to the cells in the eye
      imaginal discs. In the eye imaginal disc expressing the HA-dRFX(202-480), the G1
      S transition and/or the progression of S phase were/was interrupted, and the
      ectopic apoptosis was induced, though photoreceptor cells differentiated
      normally. These results indicate that dRFX2 plays a role in G1-S transition
      and/or in progression of S phase.

PMID- 15494452
TI  - Pyridoxal 5'-phosphate inactivates DNA topoisomerase IB by modifying the lysine
      general acid.
AB  - The present results demonstrate that pyridoxal, pyridoxal 5'-phosphate (PLP) and
      pyridoxal 5'-diphospho-5'-adenosine (PLP-AMP) inhibit Candida guilliermondii and
      human DNA topoisomerases I in forming an aldimine with the epsilon-amino group of
      an active site lysine. PLP acts as a competitive inhibitor of C.guilliermondii
      topoisomerase I (K(i) = 40 microM) that blocks the cleavable complex formation.
      Chemical reduction of PLP-treated enzyme reveals incorporation of 1 mol of PLP
      per mol of protein. The limited trypsic proteolysis releases a 17 residue peptide
      bearing a lysine-bound PLP (KPPNTVIFDFLGK*DSIR). Targeted lysine (K*) in
      C.guilliermondii topoisomerase I corresponds to that found in topoisomerase I of
      Homo sapiens (K532), Candida albicans (K468), Saccharomyces cerevisiae (K458) and
      Schizosaccharomyces pombe (K505). In the human enzyme, K532, belonging to the
      active site acts as a general acid catalyst and is therefore essential for
      activity. The spatial orientation of K532-PLP within the active site was
      approached by molecular modeling using available crystallographic data. The PLP
      moiety was found at close proximity of several active residues. PLP could be
      involved in the cellular control of topoisomerases IB. It constitutes an
      efficient tool to explore topoisomerase IB dynamics during catalysis and is also
      a lead for new drugs that trap the lysine general acid.

PMID- 15494453
TI  - Concerted bis-alkylating reactivity of clerocidin towards unpaired cytosine
      residues in DNA.
AB  - Clerocidin (CL) is a topoisomerase II poison, which cleaves DNA irreversibly at
      guanines (G) and reversibly at cytosines (C). Furthermore, the drug can induce
      enzyme-independent strand breaks at the G and C level. It has been previously
      shown that G-damage is induced by alkylation of the guanine N7, followed by
      spontaneous depurination and nucleic acid cleavage, whereas scission at C is
      obtained only after treatment with hot alkali, and no information is available to
      explain the nature of this damage. We present here a systematic study on the
      reactivity of CL towards C both in the DNA environment and in solution. Selected
      synthetic derivatives were employed to evaluate the role of each chemical group
      of the drug. The structure of CL-dC adduct was then characterized by tandem mass
      spectrometry and NMR: the adduct is a stable condensed ring system resulting from
      a concerted electrophilic attack of the adjacent carbonyl and epoxide groups of
      CL towards the exposed NH(2) and N3, respectively. This reaction mechanism, shown
      here for the first time, is characterized by faster kinetic rates than alkylation
      at G, due to the fact that the rate-determining step, alkylation at the epoxide,
      is an intramolecular process, provided a Schiff base linking CL and C can rapidly
      form, whereas the corresponding reaction of G N7 is intermolecular. These results
      provide helpful hints to explain the reversible/irreversible nature of
      topoisomerase II mediated DNA damage produced by CL at C/G steps.

PMID- 15494454
TI  - Mutually exclusive recombination of wild-type and mutant loxP sites in vivo
      facilitates transposon-mediated deletions from both ends of genomic DNA in PACs.
AB  - Recombination of wild-type and mutant loxP sites mediated by wild-type Cre
      protein was analyzed in vivo using a sensitive phage P1 transduction assay.
      Contrary to some earlier reports, recombination between loxP sites was found to
      be highly specific: a loxP site recombined in vivo only with another of identical
      sequence, with no crossover recombination either between a wild-type and mutant
      site; or between two different mutant sites tested. Mutant loxP sites of
      identical sequence recombined as efficiently as wild-type. The highly specific
      and efficient recombination of mutant loxP sites in vivo helped in developing a
      procedure to progressively truncate DNA from either end of large genomic inserts
      in P1-derived artificial chromosomes (PACs) using transposons that carry either a
      wild-type or mutant loxP sequence. PAC libraries of human DNA were constructed
      with inserts flanked by a wild-type and one of the two mutant loxP sites, and
      deletions from both ends generated in clones using newly constructed wild-type
      and mutant loxP transposons. Analysis of the results provides new insight into
      the very large co-integrates formed during P1 transduction of plasmids with loxP
      sites: a model with tri- and possibly multimeric co-integrates comprising the PAC
      plasmid, phage DNA, and transposon plasmid(s) as intermediates in the cell
      appears best to fit the data. The ability to truncate a large piece of DNA from
      both ends is likely to facilitate functionally mapping gene boundaries more
      efficiently, and make available precisely trimmed genes in their chromosomal
      contexts for therapeutic applications.

PMID- 15494455
TI  - Both CAG repeats and inverted DNA repeats stimulate spontaneous unequal sister
      chromatid exchange in Saccharomyces cerevisiae.
AB  - Genomic regions containing trinucleotide repeats (TNRs) are highly unstable, as
      the repeated sequences exhibit a high rate of mutational change, in which they
      undergo either a contraction or an expansion of repeat numbers. Although
      expansion of TNRs is associated with several human genetic diseases, the
      expansion mechanism is poorly understood. Extensive studies in model organisms
      have indicated that instability of TNRs occurs by several mechanisms, including
      replication slippage, DNA repair and recombination. In all models, the formation
      of secondary structures by disease-associated TNRs is a critical step in the
      mutation process. In this report, we demonstrate that TNRs and inverted repeats
      (IRs) both of which have the potential to form secondary structures in vivo,
      increase spontaneous unequal sister-chromatid exchange (SCE) in vegetatively
      growing yeast cells. Our results also show that TNR-mediated SCE events are
      independent of RAD50, MRE11 and RAD51, whereas IR-stimulated SCEs are dependent
      on the RAD52 epistasis-group genes. We propose that many TNR expansion mutations
      occur by SCE.

PMID- 15494456
TI  - Recombinant human thyrotropin markedly changes the 131I kinetics during 131I
      therapy of patients with nodular goiter: an evaluation by a randomized double
      blinded trial.
AB  - The present study compares, in a randomized double-blinded design, the expected
      and the actual absorbed thyroid radioactive dose in response to 0.3 mg
      recombinant human (rh)TSH (n = 35) or placebo (n = 28) given 24 h before (131)I
      therapy in patients with nodular goiter (median volume, 69 ml; range, 20-440 ml).
      The (131)I activity calculation was based on thyroid (131)I uptake (RAIU) at 24
      and 96 h after a tracer dose of 0.5 MBq (131)I. After (131)I therapy, 24- and 96
      h RAIU were repeated allowing a more exact assessment of the actual absorbed
      thyroid dose. The median (131)I activity was 617 and 632 MBq, respectively, in
      the rhTSH and the placebo group. At baseline, the 24- and 96-h RAIU and the
      expected thyroid dose were 32.8 +/- 9.1%, 32.1 +/- 8.2%, and 96.3 +/- 16.3 Gy,
      respectively, in the rhTSH group and 35.7 +/- 11.8%, 35.2 +/- 11.3%, and 94.1 +/-
      18.5 Gy, respectively, in the placebo group (P value not significant between
      groups). After (131)I therapy, the 24- and 96-h RAIU and the actual absorbed
      thyroid dose were 46.9 +/- 11.7%, 45.0 +/- 12.1%, and 136.7 +/- 47.9 Gy,
      respectively, in the rhTSH group and 33.0 +/- 11.4%, 31.0 +/- 11.3%, and 76.9 +/-
      27.5 Gy, respectively, in the placebo group (P < 0.001 between groups). Comparing
      the expected with the actual absorbed thyroid dose, this corresponds to a mean
      increase of 36.4% (95% confidence interval, 21.3-53.4) in the rhTSH group and a
      decrease of 21.5% (95% confidence interval, -33.9 to -6.6) in the placebo group
      (P < 0.001), equivalent to an increase of 73.8% in the absorbed thyroid dose in
      the rhTSH-treated group. We have thus for the first time shown that stimulation
      with rhTSH before (131)I therapy not only hinders the decrease in the thyroid
      RAIU observed with conventional (131)I therapy but in fact also significantly
      enhances the absorbed thyroid dose. Whether this also leads to a significant
      increase in goiter size reduction needs additional study.

PMID- 15494457
TI  - Age and testosterone feedback jointly control the dose-dependent actions of
      gonadotropin-releasing hormone in healthy men.
AB  - Healthy older men manifest combined declines in testosterone concentrations, LH
      secretory burst mass (amount of LH released per pulse), and feedback-sensitive
      regularity of unknown cause. To test a unifying hypothesis of simultaneous
      reductions in GnRH outflow, gonadotrope responsiveness to GnRH, and androgenic
      negative feedback, we monitored LH secretion 1) after bolus iv injection of a
      1000-fold range of randomly ordered individual doses of GnRH on separate
      mornings, 2) during unmodified (eugonadal) or testosterone-withdrawn
      (hypoandrogenemic) negative feedback, and 3) in 16 young (age, 18-35 yr) and 15
      older (age, 60-85 yr) healthy men. LH secretory burst mass and pattern regularity
      were quantitated by intensive blood sampling, high specificity LH beta-subunit
      directed immunoradiometric assay, deconvolution analysis, and approximate
      entropy. GnRH dose responsiveness was assessed by four-parameter nonlinear
      regression analysis. We demonstrated that older men exhibit 1) delayed attainment
      of GnRH-evoked maximal LH secretion; 2) enhanced potency of GnRH stimulation in
      both the feedback-intact and feedback-withdrawn states; 3) elevated gonadotrope
      sensitivity to GnRH, unmasked by experimental testosterone depletion; 4)
      comparable young adult-like GnRH efficacy, independent of testosterone feedback
      milieu; and 5) diminished regularity of GnRH-induced LH release evident only
      during unmodified androgenic feedback. We conclude that a 3-fold interaction
      among GnRH dose, testosterone concentration, and age governs GnRH action, and age
      determines both testosterone-modulated and testosterone-independent actions of
      GnRH.

PMID- 15494458
TI  - PAX8, TITF1, and FOXE1 gene expression patterns during human development: new
      insights into human thyroid development and thyroid dysgenesis-associated
      malformations.
AB  - Thyroid dysgenesis (TD) is responsible for most cases of congenital
      hypothyroidism, a condition that affects about one in 4000 newborns. Mutations in
      PAX8, TITF1, or FOXE1 may account for congenital hypothyroidism in patients with
      either isolated TD or TD with associated malformations involving kidney, lung,
      forebrain, and palate. Pax8, titf1, and foxe1 are expressed in the mouse thyroid
      bud as soon as it differentiates on the pharyngeal floor. Because the spatio
      temporal expression of these genes is unknown in humans, we decided to study them
      at different stages of human embryonic and fetal development. PAX8 and TITF1 were
      first expressed in the median thyroid primordium. Interestingly, PAX8 was also
      expressed in the thyroglossal duct and the ultimobranchial bodies. Human FOXE1
      expression was detected later than in the mouse. PAX8 was also expressed in the
      developing central nervous system and kidney, including the ureteric bud and the
      main collecting ducts. TITF1 was expressed in the ventral forebrain and lung.
      FOXE1 expression was detected in the oropharyngeal epithelium and thymus. In
      conclusion, the expression patterns described here show some differences from
      those reported in the mouse. They explain the malformations associated with TD in
      patients carrying PAX8, TITF1, and FOXE1 gene mutations.

PMID- 15494459
TI  - Hemostatic risk factors and insulin sensitivity, regional body fat distribution,
      and the metabolic syndrome.
AB  - Disturbances in the thrombotic and fibrinolytic systems are a feature of insulin
      resistance, obesity, and the metabolic syndrome. However, there are few studies
      in which these relationships have been explored in mainly asymptomatic
      individuals using sophisticated measures of insulin sensitivity and regional
      adiposity. Variables of the hemostatic system were measured in 106 men (aged 32
      68 yr; body mass index, 20-34 kg/m(2)). Insulin sensitivity was measured by
      minimal model analysis and regional adiposity by dual energy x-ray
      absorptiometry. Clustering of intercorrelated variables was assessed by the
      statistical technique of factor analysis. Plasma levels of procoagulant factors
      VII and X, anticoagulant proteins C and S, and plasminogen activator inhibitor-1
      correlated positively with total and percent central body fat (r = 0.25-0.38; P <
      0.05) and negatively with insulin sensitivity (except protein S; r = -0.24 to 
      0.35; P < 0.05). On factor analysis, procoagulant factors VII and X, proteins C
      and S, and plasminogen activator inhibitor-1 were components of the cluster of
      variables that explained the greatest proportion of the variance in the data
      (39.2%). Other variables included in this cluster were those typical of the
      metabolic syndrome and also serum gamma-glutamyl transferase activity. These
      results suggest that factors VII and X and proteins C and S are features of the
      intercorrelated disturbances of the metabolic syndrome. Associations with
      adiposity and liver enzyme activity suggest the involvement of hepatic fat
      deposition.

PMID- 15494460
TI  - Corticotropin-releasing hormone directly stimulates cortisol and the cortisol
      biosynthetic pathway in human fetal adrenal cells.
AB  - Near term the human fetal adrenals (HFAs) initiate production of cortisol, which
      promotes organ maturation and acts to increase placental CRH biosynthesis. The
      objective of the present study was to determine whether CRH directly stimulates
      both cortisol production and expression of the steroidogenic enzymes in HFA
      definitive zone cells. CRH stimulated the production of cortisol in a time- and
      dose-dependent manner, with an effective concentration of as low as 0.01 nm. In
      real-time RT-PCR experiments, CRH treatment increased the mRNA levels of
      steroidogenic acute regulatory protein and each of the enzymes needed to produce
      cortisol. CRH induced 3beta-hydroxysteroid dehydrogenase type II (HSD3B2) by 34
      fold, 21-hydroxylase (CYP21) by 55-fold, and 11beta-hydroxylase by 41-fold.
      Induction of steroidogenic acute regulatory protein, cholesterol side chain
      cleavage (CYP11A), and 17alpha-hydroxylase (CYP17) mRNA by CRH was 6-, 4-, and 6
      fold, respectively. We also demonstrated that submaximal concentrations of CRH
      (30 pm) and ACTH (30 pm) that are seen in fetal circulation were additive on
      cortisol biosynthesis and 3beta-hydroxysteroid dehydrogenase type II mRNA
      induction. We suggest that CRH may play an important role in the late gestational
      rise in cortisol secretion from the HFAs, which may serve to augment placental
      CRH production and therefore participate in the endocrine cascade that is
      involved in fetal organ maturation and potentially in the timing of human
      parturition.

PMID- 15494461
TI  - HOXA10, Pbx2, and Meis1 protein expression in the human endometrium: formation of
      multimeric complexes on HOXA10 target genes.
AB  - HOXA10 is a transcription factor necessary for embryonic uterine development and
      for adult endometrial receptivity. The three-amino acid loop extension family of
      cofactors, including Pbx and Meis, provide HOX target gene specificity in
      development and myeloid differentiation. Here we demonstrate the expression of
      Pbx and Meis family cofactors in the human endometrium and their interaction with
      HOXA10. Using immunohistochemical analysis, we found that Pbx2 and Meis1, but not
      Pbx1, Pbx3, or Meis2, were expressed in human endometrium. HOXA10, Pbx2, and
      Meis1 were expressed in the stroma throughout the menstrual cycle. The glandular
      expression of HOXA10 and Meis1 was menstrual cycle stage specific, whereas
      glandular Pbx2 expression did not vary. Pbx2, but not Meis1, was expressed in
      Ishikawa cells. EMSA demonstrated HOXA10-Pbx2 binding as a heterodimer to an
      enhancer of the EMX2 gene, a known target of HOXA10 regulation. Ablation of the
      Pbx binding site, but not ablation of the HOXA10 binding site in EMX2, resulted
      in loss of dimer binding. Based on the observed expression and binding patterns
      of Pbx2, Meis1, and HOXA10, it is likely that heterodimeric and trimeric
      complexes involving these proteins determine HOXA10 target gene specificity.
      Enhanced target gene specificity imparted by multimer binding is likely necessary
      for HOXA10-mediated endometrial receptivity.

PMID- 15494462
TI  - Expression and activity of 20alpha-hydroxysteroid dehydrogenase (AKR1C1) in
      abdominal subcutaneous and omental adipose tissue in women.
AB  - We examined the expression and activity of 20alpha-hydroxysteroid dehydrogenase
      (20alpha-HSD) in abdominal adipose tissue in women. This recently characterized
      enzyme from the aldoketoreductase 1C family is responsible for the conversion of
      progesterone into 20alpha-hydroxyprogesterone. Abdominal sc (SC) and omental (OM)
      adipose tissue biopsies were obtained from a sample of 32 women aged 47.7 +/- 5.9
      yr (body mass index 27.6 +/- 5.0 kg/m(2)) undergoing abdominal hysterectomies.
      Body composition and body fat distribution measurements were performed before the
      surgery by dual-energy x-ray absorptiometry and computed tomography,
      respectively. The expression of 20alpha-HSD was determined by real-time RT-PCR,
      and its activity was measured in whole-tissue homogenates. mRNA and activity of
      the enzyme were detected in both the SC and OM fat depots, the two measures being
      significantly higher in the SC compartment. Women characterized by a visceral
      adipose tissue area of 100 cm(2) or greater had an increased 20alpha-HSD
      conversion rate in their OM adipose tissue, compared with women without visceral
      obesity (13.99 +/- 2.07 vs. 7.92 +/- 0.83 fmol/microg protein per 24 h, P <
      0.05). Accordingly, a positive correlation was found between OM adipose tissue
      20alpha-HSD activity and computed tomography-measured visceral adipose tissue
      area (r = 0.36, P < 0.05). Significant positive correlations were also found
      between OM 20alpha-HSD activity and OM adipocyte diameter (r = 0.49, P < 0.05)
      and OM adipose tissue LPL activity (r = 0.36, P = 0.06). In conclusion, 20alpha
      HSD activity and mRNA were detected in SC and OM adipose tissue in women, and OM
      20alpha-hydroxylation of progesterone was highest in women with visceral obesity.
      Additional studies are required to establish whether local conversion of
      progesterone may impact on the metabolism and function of adipocytes located
      within the abdominal cavity.

PMID- 15494463
TI  - Platelet hyperactivation in maintained growth hormone-deficient childhood
      patients after therapy withdrawal as a putative earlier marker of increased
      cardiovascular risk.
AB  - GH deficiency (GHD) is associated with a higher risk of vascular disease, whose
      pathophysiological mechanisms remains not yet fully elucidated. This study aimed
      to assess the main cardiovascular risk indexes, plasma catecholamines content,
      and the platelet function in childhood-onset GHD patients. Some of the main
      clinical examinations related with cardiovascular risk, plasma catecholamines
      content, as well as platelet intracellular free calcium concentration
      ([Ca(2+)](i)), whole-blood aggregation, and morphology were evaluated in
      childhood-onset GHD patients treated with GH for a variable period and off GH
      therapy for at least 2 yr before entry into study and in sex-, age-, and body
      mass index-matched control groups. Among the patients, group 1 (GHD-1) has
      recovered GH levels after withdrawal, whereas group 2 (GHD-2) has remained GH
      deficient. Minor differences on the cardiovascular risk indexes were observed
      between the groups. Plasma catecholamine concentrations in the GHD groups did not
      statistically differ from the control group, but higher adrenaline content was
      observed in the GHD-2 group when compared with the GHD-1 one. Basal and thrombin
      evoked [Ca(2+)](i) and platelet aggregation were identical between the GHD-1
      group and the matched control. However, the GHD-2 group has increased thrombin
      evoked [Ca(2+)](i) (297.0 +/- 15.7 Deltanmol/liter; P < 0.01), collagen, and ADP
      induced platelet aggregation (33.3 +/- 4.3 and 12.5 +/- 2.1 Omega, respectively;
      P < 0.05) vs. the control-2 group (Delta[Ca(2+)](i): 102.1 +/- 13.6
      Deltanmol/liter; aggregation: 19.6 +/- 2.9 and 6.2 +/- 0.8 Omega). The platelet
      hyperreactivity state in the GHD-2 was reinforced by morphologic studies of
      electron microscopy. In conclusion, there were minor differences between the GHD
      1 group and the controls, which might be due to the recovery of GH levels after
      therapy withdrawal. However, the maintained GHD group, despite minor
      cardiovascular risk index differences, has increased [Ca(2+)](i) and aggregation,
      which could indicate a hyperactivation state that might be viewed as an earlier
      marker of cardiovascular disturbances.

PMID- 15494464
TI  - Epidermal growth factor receptor inhibition by tyrphostin 51 induces apoptosis in
      luteinized granulosa cells.
AB  - Growth factors may be involved in the control of ovarian cell fate and could
      contribute to regulation of ovarian cell apoptosis. Our objective is to test the
      hypothesis that, in human luteinized granulosa cells, epidermal growth factor
      (EGF) works through the MAPK signaling pathway and inhibition of EGF receptor by
      a specific tyrosine kinase inhibitor, tyrphostin 51, will inhibit the activation
      of MAPK and induce apoptosis. Luteinized granulosa cells from human in vitro
      fertilization aspirates were treated as follows: 1) vehicle
      (dimethylsulfoxide:ethanol), 2) EGF, 3) tyrphostin 51, and 4) tyrphostin 51 plus
      EGF. Blockage of EGF receptor by tyrphostin 51 reduced the MAPK activity and
      inhibited phosphorylation and nuclear translocation of activated MAPK. Blockage
      of EGF receptor also induced apoptosis as demonstrated by the activation of
      caspase-3, an executioner protease of the apoptotic pathway, and by an increased
      percentage of subdiploid apoptotic nuclei. These results support the hypothesis
      that in human luteinized granulosa cells, EGF works through the MAPK signaling
      pathway and that its inhibition by tyrphostin 51 inhibits MAPK phosphorylation
      and induces apoptotic nuclear changes. Our data thus provide additional
      information regarding regulation of apoptosis in luteinized granulosa cells.

PMID- 15494465
TI  - Mechanical stretch up-regulates the human oxytocin receptor in primary human
      uterine myocytes.
AB  - Oxytocin receptor (OTR) expression is increased before the onset of labor in all
      models of parturition. However, the mechanisms responsible for the increase in
      OTR expression are uncertain. Animal data suggest that uterine stretch increases
      OTR mRNA expression. In primary cultures of human uterine smooth muscle cells
      obtained from nonpregnant (NP) women and pregnant women before (NL) and after (L)
      the onset of labor, we investigated the effect of stretch on the expression of
      OTR mRNA and DNA binding of activator protein-1 (AP-1), CCAAT/enhancer binding
      protein (C/EBP)beta, and nuclear factor-kappaB transcription factors. OTR
      expression was least in NL, intermediate in NP, and greatest in L cells. Stretch
      of NL cells resulted in up-regulation of OTR mRNA expression associated with
      increased OTR gene promoter activity. Stretch of NP and L cells did not affect
      OTR mRNA expression. The increased promoter activity was associated with
      increased DNA binding of C/EBP and AP-1 but not nuclear factor-kappaB
      transcription factors. Overexpression of C/EBP, but not AP-1, increased OTR
      promoter activity. We conclude that stretch of NL cells results in increased OTR
      mRNA expression probably through increased C/EBPbeta DNA binding. These data
      suggest that stretch contributes to the massive increase in OTR expression before
      the onset of human labor.

PMID- 15494466
TI  - Protection of bone mass by estrogens and raloxifene during exercise-induced
      weight Loss.
AB  - The aim of this study was to determine whether estrogen and/or raloxifene help to
      conserve bone mineral density (BMD) during moderate weight loss. Postmenopausal
      women (n = 68) participated in a 6-month weight loss program that consisted
      primarily of supervised exercise training. Another 26 women were studied over 6
      months of weight stability. All participants were randomized to three treatment
      arms: placebo, raloxifene (60 mg/d), or hormone therapy (HT; conjugated
      estrogens, 0.625 mg/d; trimonthly medroxyprogesterone acetate, 5 mg/d for 13 d,
      for women with a uterus). Changes in body weight (mean +/- se) averaged 0.8 +/-
      0.5 kg in the weight-stable group and -4.1 +/- 0.4 kg in the weight loss group.
      Across all measured skeletal sites, average changes in BMD in weight stable women
      were -0.6 +/- 1.1% (n = 7), 0.9 +/- 0.6% (n = 9), and 3.0 +/- 0.7% (n = 10) in
      the placebo, raloxifene, and HT groups, respectively; comparable BMD changes in
      the weight loss groups were -1.5 +/- 0.5% (n = 22), -0.5 +/- 0.5% (n = 23), and
      1.1 +/- 0.4% (n = 23). There were no significant interactions between weight loss
      and drug treatment on changes in BMD, but there were significant main effects of
      weight loss on lumbar spine (P = 0.022), total hip (P = 0.010), and trochanter
      BMD (P < 0.001). These findings suggest that weight loss, even when modest in
      magnitude and induced by exercise training, causes a reduction in BMD,
      particularly in women not taking raloxifene or HT. It is not known whether
      reductions in BMD of this magnitude increase the risk for osteoporotic fracture.

PMID- 15494467
TI  - Cigarette smoke in research.

PMID- 15494469
TI  - Smoke gets in your cells.

PMID- 15494470
TI  - Vascular ischaemia and reperfusion injury.
AB  - Although restoration of blood flow to an ischaemic organ is essential to prevent
      irreversible tissue injury, reperfusion per se may result in a local and systemic
      inflammatory response that may augment tissue injury in excess of that produced
      by ischaemia alone. Cellular damage after reperfusion of previously viable
      ischaemic tissues is defined as ischaemia-reperfusion (I-R) injury. I-R injury is
      characterized by oxidant production, complement activation, leucocyte-endothelial
      cell adhesion, platelet-leucocyte aggregation, increased microvascular
      permeability and decreased endothelium-dependent relaxation. In its severest
      form, I-R injury can lead to multiorgan dysfunction or death. Although our
      understanding of the pathophysiology of I-R injury has advanced significantly in
      the last decade, such experimentally derived concepts have yet to be fully
      integrated into clinical practice. Treatment of I-R injury is also confounded by
      the fact that inhibition of I-R-associated inflammation might disrupt protective
      physiological responses or result in immunosuppression. Thus, while timely
      reperfusion of the ischaemic area at risk remains the cornerstone of clinical
      practice, therapeutic strategies such as ischaemic preconditioning, controlled
      reperfusion, and anti-oxidant, complement or neutrophil therapy may significantly
      prevent or limit I-R-induced injury in humans.

PMID- 15494471
TI  - The contribution of fetal metabolism to the disposition of morphine.
AB  - The contribution of fetal metabolism to drug disposition in pregnancy is poorly
      understood. With maternal administration of morphine, like many drugs, steady
      state concentrations in fetal plasma are less than in maternal plasma. The
      contribution of fetal metabolism to this difference is unknown. Morphine was used
      as a model drug to test the hypothesis that fetal metabolism contributes
      significantly to drug clearance by the fetus. Infusions of morphine, morphine-3
      beta-glucuronide (M3G), and morphine-6-beta-glucuronide (M6G) were administered
      to the fetal baboon. Plasma concentrations of drug and metabolite obtained near
      steady state were measured by high-performance liquid chromatography. During
      morphine infusion, morphine, M3G, and M6G concentrations rose linearly with dose.
      M3G concentrations exceeded M6G by 20-fold. Mean +/- S.D. clearances of morphine,
      M3G, and M6G from the fetus were 69 +/- 17, 2.3 +/- 0.60, and 1.6 +/- 0.24 ml x
      min(-1), respectively. Clearances seemed to be dose-independent. The mean +/-
      S.D. fraction of morphine dose metabolized was 32 +/- 5.5%. This converts to a
      fetal metabolic clearance of 22 +/- 6.5 ml x min(-1). In conclusion, one third of
      the elimination of morphine from the fetal baboon is attributable to metabolism,
      one third to passive placental transfer, and one third undefined. Furthermore,
      there is no evidence for saturation of metabolism. Fetal metabolism is
      surprisingly high compared with in vitro estimates of metabolism and morphine
      clearance in human infants. For morphine, fetal drug metabolism accounts for half
      the difference between fetal and maternal plasma concentrations.

PMID- 15494472
TI  - Xenobiotic and endobiotic transporter mRNA expression in the blood-testis
      barrier.
AB  - A major function of xenobiotic and endobiotic transporters is to move a wide
      range of organic substances across cell membranes. Sertoli cells play an
      important role in protecting developing germ cells by forming a physiological
      barrier, limiting exposure to potentially toxic substrates, or conversely,
      facilitating uptake of xenobiotics within the testis. The aim of this study was
      to quantitatively determine the constitutive expression of various transporters
      in isolated Sertoli cells from adult Sprague-Dawley rats. The following mRNA
      levels were measured in isolated Sertoli cells by the branched DNA signal
      amplification method, multidrug resistance (Mdr) protein 1a, 1b, and 2; multiple
      drug resistance protein (Mrp) 1, 2, 3, 4, 5, 6, 7, and 8; sodium taurocholate
      cotransporting polypeptide; bile salt excretory protein; ileal bile acid
      transporter; AbcG5 and AbcG8; organic anion transporting polypeptide (Oatp) 1, 2,
      3, 4, 5, 9, and 12; prostaglandin transporter (Pgt); testis-specific transporter
      (Tst) 1 and Tst2; organic anion transporter (Oat) 1, 2, 3, and K; organic cation
      transporter (Oct) 1, 2, 3, N1, and N2; divalent metal transporter (Dmt) 1,
      Menke's, and Wilson's; zinc transporter (Znt) 1; equilibrative nucleoside
      transporter (Ent) 1 and 2; concentrative nucleoside transporter (Cnt) 1 and 2;
      and peptide transporter (Pept) 1 and 2. Levels were also determined in whole
      testis, liver, kidney, and ileum to provide a reference for determining relative
      expression levels. Mrp8, Tst1 and 2, and Ent1 and 2 were expressed in Sertoli
      cells at higher levels than in liver, kidney, or ileum, whereas Mrp1, 5, and 7,
      Mdr2, Oatp3, Oat2, OctN2, Dmt1, Menke's, Wilson's, and Znt1 were all
      significantly expressed in Sertoli cells, but Sertoli cell expression was not the
      tissue of highest expression. The remaining transporters were expressed at low
      levels in isolated Sertoli cells. Additionally, expression levels of Mrp1, Mrp7,
      Mrp8, Tst1, Tst2, OctN2, Wilson's, Znt1, Ent1, and Ent2 were greater in isolated
      Sertoli cells than in whole testis. Constitutive expression of transporters in
      Sertoli cells may provide an insight into the range of xenobiotics that can
      potentially be transported by Sertoli cells and thereby provide a mechanistic
      under standing of blood-testis barrier function.

PMID- 15494473
TI  - Phenotypic variation in cardiovascular responses to acute hypoxic and hypercapnic
      exposure in mice.
AB  - The impact of genetic variation on cardiovascular responses to hypoxia and
      hypercapnia is not well understood. Therefore, we determined the acute changes in
      systemic arterial blood pressure (P(SA)) and heart rate (HR) in seven strains of
      commonly used inbred mice exposed to acute periods of hypoxia (10% O(2)),
      hypercapnia (5% CO(2)), and hypoxia/hypercapnia (10% O(2) + 5% CO(2)) during
      wakefulness. Hypercapnia induced an essentially homogeneous response across
      strains, with P(SA) maintained at or slightly above baseline and with HR
      exhibiting a typical baroreceptor-mediated bradycardia. In contrast, exposure to
      hypoxia elicited a marked heterogeneity in cardiovascular responses between
      strains. The change in P(SA) during hypoxia ranged from maintenance of
      normotension in the FVB/J strain to profound hypotension of approximately 30 mmHg
      in the DBA/2J strain. HR responses were highly variable between strains during
      hypoxia, and with the exception of the DBA/2J strain that exhibited significant
      bradyarrhythmias and consequent hypotension, the HR responses were unrelated to
      changes in P(SA). The P(SA) response to combined hypoxia/hypercapnia represented
      a balance of the hypertension of hypercapnia and the hypotension of hypoxia in
      six of the seven strains. In the FVB/J strain, combined hypoxia/hypercapnia
      produced a hypertensive response that was greater than that of hypercapnia alone.
      These results suggest that genetic background affects the cardiovascular response
      to hypoxia, but not hypercapnia.

PMID- 15494474
TI  - Uteroplacental insufficiency induces site-specific changes in histone H3 covalent
      modifications and affects DNA-histone H3 positioning in day 0 IUGR rat liver.
AB  - Uteroplacental insufficiency and subsequent intrauterine growth retardation
      (IUGR) increase the risk of adult onset insulin resistance and dyslipidemia in
      humans and rats. IUGR rats are further characterized by postnatal alterations in
      hepatic PPAR-gamma coactivator (PGC-1) and carnitine-palmitoyl-transferase I
      (CPTI) expression, as well as overall hyperacetylation of histone H3. However, it
      is unknown whether the histone H3 hyperacetylation is site specific or relates to
      the changes in gene expression previously described in IUGR rats. We therefore
      hypothesized that uteroplacental insufficiency causes site-specific modifications
      in hepatic H3 acetylation and affects the association of acetylated histone H3
      with PGC-1 and CPTI promoter sequences. Uteroplacental insufficiency was used to
      produce asymmetrical IUGR rats. IUGR significantly increased acetylation of H3
      lysine-9 (H3/K9), lysine-14 (H3/K14), and lysine-18 (H3/K18) at day 0 of life,
      and these changes occurred in association with decreased nuclear protein levels
      of histone deacetylase 1 (HDAC1) and HDAC activity. Chromatin immunoprecipitation
      using acetyl-H3/K9 antibody and day 0 chromatin revealed that uteroplacental
      insufficiency affected the association between acetylated H3/K9 and the promoters
      of PGC-1 and CPTI, respectively, in IUGR liver. At day 21 of life, the neonatal
      pattern of H3 hyperacetylation persisted only in the IUGR males. We conclude that
      uteroplacental insufficiency increases H3 acetylation in a site-specific manner
      in IUGR liver and that these changes persist in male IUGR animals. The altered
      association of the PGC-1 and CPTI promoters with acetylated H3/K9 correlates with
      previous reports of IUGR altering the expression of these genes. We speculate
      that in utero alterations of chromatin structure contribute to fetal programming.

PMID- 15494475
TI  - Ischemic but not pharmacological preconditioning elicits a gene expression
      profile similar to unprotected myocardium.
AB  - Pharmacological (PPC) and ischemic preconditioning (IschPC) provide comparable
      protection against ischemia in the heart. However, the genomic phenotype may
      depend on the type of preconditioning. Isolated perfused rat hearts were used to
      evaluate transcriptional responses to PPC and IschPC in the presence
      (mediator/effector response) or absence (trigger response) of 40 min of test
      ischemia using oligonucleotide microarrays. IschPC was induced by 3 cycles of 5
      min of ischemia, and PPC by 15 min of 2.1 vol% isoflurane. Unsupervised analysis
      methods were used to identify gene expression patterns. PPC and IschPC were
      accompanied by marked alterations in gene expression. PPC and IschPC shared only
      approximately 25% of significantly up- and downregulated genes after triggering.
      The two types of preconditioning induced a more uniform genomic response after
      ischemia/reperfusion. Numerous genes separated preconditioned from unprotected
      ischemic hearts. Three stable gene clusters were identified in the trigger
      response to preconditioning, while eight stable clusters related to
      cytoprotection, inflammation, remodeling, and long interspersed nucleotide
      elements (LINEs) were delineated after prolonged ischemia. A single stable sample
      cluster emerged from cluster analysis for both IschPC and unprotected myocardium,
      indicating a close molecular relationship between these two treatments. Principal
      component analysis revealed differences between PPC vs. IschPC, and trigger vs.
      mediator/effector responses in transcripts predominantly related to biosynthesis
      and apoptosis. IschPC and PPC similarly but distinctly reprogram the genetic
      response to ischemic injury. IschPC elicits a postischemic gene expression
      profile closer to unprotected myocardium than PPC, which may be therefore more
      advantageous as therapeutic strategy in cardioprotection.

PMID- 15494477
TI  - When two-dimensional structure led the way.

PMID- 15494476
TI  - Rapid evolution and diversification of mammalian alpha-defensins as revealed by
      comparative analysis of rodent and primate genes.
AB  - Mammalian alpha-defensins constitute a family of cysteine-rich, cationic
      antimicrobial peptides produced by phagocytes and intestinal Paneth cells,
      playing an important role in innate host defense. Following comprehensive
      computational searches, here we report the discovery of complete repertoires of
      the alpha-defensin gene family in the human, chimpanzee, rat, and mouse with new
      genes identified in each species. The human genome was found to encode a cluster
      of 10 distinct alpha-defensin genes and pseudogenes expanding 132 kb continuously
      on chromosome 8p23. Such alpha-defensin loci are also conserved in the syntenic
      chromosomal regions of chimpanzee, rat, and mouse. Phylogenetic analyses showed
      formation of two distinct clusters with primate alpha-defensins forming one
      cluster and rodent enteric alpha-defensins forming the other cluster. Species
      specific clustering of genes is evident in nonprimate species but not in the
      primates. Phylogenetically distinct subsets of alpha-defensins also exist in each
      species, with most subsets containing multiple members. In addition, natural
      selection appears to have acted to diversify the functionally active mature
      defensin region but not signal or prosegment sequences. We concluded that
      mammalian alpha-defensin genes may have evolved from two separate ancestors
      originated from beta-defensins. The current repertoires of the alpha-defensin
      gene family in each species are primarily a result of repeated gene duplication
      and positive diversifying selection after divergence of mammalian species from
      each other, except for the primate genes, which were evolved prior to the
      separation of the primate species. We argue that the presence of multiple,
      divergent subsets of alpha-defensins in each species may help animals to better
      cope with different microbial challenges in the ecological niches which they
      inhabit.

PMID- 15494478
TI  - The covalent structure of an entire gamma G immunoglobulin molecule. 1969.

PMID- 15494479
TI  - Mechanisms of soluble cytokine receptor generation.
AB  - Soluble cytokine receptors regulate inflammatory and immune events by functioning
      as agonists or antagonists of cytokine signaling. As such, they act within
      complex receptor systems that include signaling receptors, nonsignaling decoy
      receptors, receptor-associated proteins, and soluble receptor antagonists.
      Soluble cytokine receptors can be generated by several mechanisms, which include
      proteolytic cleavage of receptor ectodomains, alternative splicing of mRNA
      transcripts, transcription of distinct genes that encode soluble cytokine-binding
      proteins, release of full-length receptors within the context of exosome-like
      vesicles, and cleavage of GPI-anchored receptors. Furthermore, the important role
      of soluble cytokine receptors in regulating host defense mechanisms is evidenced
      by viruses that encode soluble homologues of mammalian receptors and thereby
      evade innate host immune responses via the sequestration of essential cytokines.

PMID- 15494480
TI  - Cutting edge: engagement of CD160 by its HLA-C physiological ligand triggers a
      unique cytokine profile secretion in the cytotoxic peripheral blood NK cell
      subset.
AB  - CD160 is an Ig-like activating NK cell receptor expressed on the majority of
      circulating NK cells. This population corresponds to the nonproliferating, highly
      cytolytic, CD56dimCD16+ subset. CD160 engagement by HLA-C molecules mediates
      cytotoxic function. In this study, we report that upon specific activation by the
      physiological ligand HLA-C, or Ab cross-linking, CD160+ peripheral blood NK cells
      produce IFN-gamma, TNF-alpha, and IL-6. This unique CD160-mediated cytokine
      production differs from the one observed after CD16 engagement whose expression
      is also restricted to the CD56dim cytotoxic NK cell subset. As already reported
      for the CD160-mediated cytotoxic effector function, CD160-mediated cytokine
      production by peripheral blood-NK cells is negatively controlled by the killer Ig
      like receptor CD158b. Thus, the CD160 receptor represents a unique triggering
      surface molecule expressed by cytotoxic NK cells that participates in the
      inflammatory response and determines the type of subsequent specific immunity.

PMID- 15494481
TI  - Cutting edge: identification of hepatitis C virus-specific CD8+ T cells
      restricted by donor HLA alleles following liver transplantation.
AB  - By necessity, human liver transplantation is performed across HLA barriers. As a
      result, intracellular infection of the allograft presents a unique immunologic
      challenge for the recipient's immune system. In this study, we describe the
      presence of HLA-A2-restricted, hepatitis C virus (HCV)-specific CD8+ T cells in
      liver transplant recipients in whom the allograft is HLA-A2 positive and the
      recipient is HLA-A2 negative. These memory-effector T cells are recipient derived
      and recognize HCV peptide uniquely in the context of HLA-A2. Furthermore, these
      cells were absent before the transplant, suggesting that the allograft is capable
      of selectively expanding naive CD8+ T cells. The in vitro specificity to donor
      HLA allele-restricted CD8+ T cells suggests that these cells may function to
      control HCV spread in the allograft.

PMID- 15494482
TI  - Regulation of B cell differentiation and plasma cell generation by IL-21, a novel
      inducer of Blimp-1 and Bcl-6.
AB  - IL-21 is a type I cytokine whose receptor is expressed on T, B, and NK cells.
      Within the B cell lineage, IL-21 regulates IgG1 production and cooperates with IL
      4 for the production of multiple Ab classes in vivo. Using IL-21-transgenic mice
      and hydrodynamics-based gene delivery of IL-21 plasmid DNA into wild-type mice as
      well as in vitro studies, we demonstrate that although IL-21 induces death of
      resting B cells, it promotes differentiation of B cells into postswitch and
      plasma cells. Thus, IL-21 differentially influences B cell fate depending on the
      signaling context, explaining how IL-21 can be proapoptotic for B cells in vitro
      yet critical for Ag-specific Ig production in vivo. Moreover, we demonstrate that
      IL-21 unexpectedly induces expression of both Blimp-1 and Bcl-6, indicating
      mechanisms as to how IL-21 can serve as a complex regulator of B cell maturation
      and terminal differentiation. Finally, BXSB-Yaa mice, which develop a systemic
      lupus erythematosus-like disease, have greatly elevated IL-21, suggesting a role
      for IL-21 in the development of autoimmune disease.

PMID- 15494483
TI  - Vaccination in humans generates broad T cell cytokine responses.
AB  - In recent years, the quantification of T cell responses to pathogens or
      immunogens has become a common tool in the evaluation of disease pathogenesis or
      vaccine immunogenicity. Such measurements are usually limited to enumerating IFN
      gamma-producing cells after ex vivo stimulation with Ag, but little is known
      about the phenotype or complete functional repertoire of the Ag-specific cells.
      We used 12-color flow cytometry to characterize Ag-specific T cells elicited by
      vaccines or natural infection to determine lineage and differentiation status as
      well as the capacity to produce four cytokines (IFN-gamma, TNF-alpha, IL-2, and
      IL-4) and a chemokine (MIP1beta). As expected, responding cells had a typical
      memory phenotype; however, the cytokine profiles associated with the responses
      were highly complex. The pattern of cytokine coexpression in response to specific
      Ags was a skewed subset of the complete repertoire (revealed by polyclonal
      stimulation). We found significant differences in the patterns of cytokines
      elicited by vaccination (where IFN-gamma was by far a subdominant response) vs
      natural infection; in addition, there was fairly significant intersubject
      variation. Our findings illustrate the limitation of the evaluation of immune
      responses using single functional measurements (such as IFN-gamma); in fact, it
      is likely that sensitive evaluation of Ag-specific T cells will require the
      coordinate measurement of several cytokines. The presence and variability of
      these complex response profiles introduce the possibility that selective
      functional expression patterns may provide correlates for vaccine efficacy or
      disease progression.

PMID- 15494484
TI  - Deranged early T cell development in immunodeficient strains of nonobese diabetic
      mice.
AB  - NOD mice exhibit defects in T cell functions that have been postulated to
      contribute to diabetes susceptibility in this strain. However, early T cell
      development in NOD mice has been largely unexplored. NOD mice with the scid
      mutation and Rag1 deficiency were analyzed for pre-T cell development in the NOD
      genetic background. These strains reveal an age-dependent, programmed breakdown
      in beta selection checkpoint enforcement. At 5-8 wk of age, even in the absence
      of TCRbeta expression, CD4+ and CD4+CD8+ blasts appear spontaneously. However,
      these breakthrough cells fail to restore normal thymic cellularity. The
      breakthrough phenotype is recessive in hybrid (NODxB6)F1-scid and -Rag1null mice.
      The breakthrough cells show a mosaic phenotype with respect to components of the
      beta selection program. They mimic normal beta selection by up-regulating
      germline TCR-Calpha transcripts, CD2, and Bcl-xL and down-regulating Bcl-2.
      However, they fail to down-regulate transcription factors HEB-alt and Hes1 and
      initially express aberrantly high levels of Spi-B, c-kit (CD117), and IL-7Ralpha.
      Other genes examined distinguish this form of breakthrough from previously
      reported models. Some of the abnormalities appear first in a cohort of postnatal
      thymocytes as early as the double-negative 2/double-negative 3 transitional
      stage. Thus, our results reveal an NOD genetic defect in T cell developmental
      programming and checkpoint control that permits a subset of the normal outcomes
      of pre-TCR signaling to proceed even in the absence of TCRbeta rearrangement.
      Furthermore, this breakthrough may initiate thymic lymphomagenesis that occurs
      with high frequency in both NOD-scid and -Rag1null mice.

PMID- 15494485
TI  - CD28 and lipid rafts coordinate recruitment of Lck to the immunological synapse
      of human T lymphocytes.
AB  - In T lymphocytes, the Src family kinase Lck associates lipid rafts and
      accumulates at the immunological synapse (IS) during T cell stimulation by APCs.
      Using CD4- or CD28-deficient murine T cells, it was suggested that recruitment of
      Lck to the IS depends on CD4, whereas CD28 sustains Lck activation. However, in
      human resting T cells, CD28 is responsible for promoting recruitment of lipid
      rafts to the IS by an unknown mechanism. Thus, we performed a series of
      experiments to determine 1) whether Lck is recruited to the IS through lipid
      rafts; and 2) whether Lck recruitment to the IS of human resting T cells depends
      on CD4 or on CD28 engagement. We found that CD28, but not CD4, stimulation
      induced recruitment of Lck into detergent-resistant domains as well as its
      accumulation at the IS. We also found that Lck recruitment to the IS depends on
      the CD28 COOH-terminal PxxPP motif. Thus, the CD28-3A mutant, generated by
      substituting the prolines in positions 208, 211, and 212 with alanines, failed to
      induce Lck and lipid raft accumulation at the synapse. These results indicate
      that CD28 signaling orchestrates both Lck and lipid raft recruitment to the IS to
      amplify T cell activation.

PMID- 15494486
TI  - Beta-defensin-2 expression is regulated by TLR signaling in intestinal epithelial
      cells.
AB  - The intestinal epithelium serves as a barrier to the intestinal flora. In
      response to pathogens, intestinal epithelial cells (IEC) secrete proinflammatory
      cytokines. To aid in defense against bacteria, IEC also secrete antimicrobial
      peptides, termed defensins. The aim of our studies was to understand the role of
      TLR signaling in regulation of beta-defensin expression by IEC. The effect of LPS
      and peptidoglycan on beta-defensin-2 expression was examined in IEC lines
      constitutively or transgenically expressing TLRs. Regulation of beta-defensin-2
      was assessed using promoter-reporter constructs of the human beta-defensin-2
      gene. LPS and peptidoglycan stimulated beta-defensin-2 promoter activation in a
      TLR4- and TLR2-dependent manner, respectively. A mutation in the NF-kappaB or AP
      1 site within the beta-defensin-2 promoter abrogated this response. In addition,
      inhibition of Jun kinase prevents up-regulation of beta-defensin-2 protein
      expression in response to LPS. IEC respond to pathogen-associated molecular
      patterns with expression of the antimicrobial peptide beta-defensin-2. This
      mechanism may protect the intestinal epithelium from pathogen invasion and from
      potential invaders among the commensal flora.

PMID- 15494487
TI  - Rapid induction of splenic and peritoneal B-1a cells in adult mice by thymus
      independent type-2 antigen.
AB  - We have produced a transgenic mouse (PV1TgL) that can only generate B lymphocytes
      with an Ig receptor specific for the synthetic polymer polyvinyl pyrrolidinone.
      Before immunization, bone marrow B cell numbers are very low, and peripheral
      lymphoid organs are almost devoid of B cells, confirming the role of positive
      selection by Ag in the development of mature B cell populations. The predominant
      population of B cells in the spleens of naive adult PV1TgL mice have most of the
      characteristics of marginal zone B cells, including anatomical location in the
      peripheral areas of the splenic white pulp. After immunization, a new population
      of B cells appears in the spleen with the characteristics of B-1 cells. Similar
      cells also appear somewhat later in the peritoneal cavity. Our findings suggest
      that immunization with a thymus-independent Ag can lead to the appearance and
      expansion of Ag-reactive B-1 cells in an adult mouse.

PMID- 15494488
TI  - Transgenic expression of CTLA-4 controls lymphoproliferation in IL-2-deficient
      mice.
AB  - IL-2-deficient mice develop a lymphoproliferative and autoimmune disease
      characterized by autoimmune hemolytic anemia (AHA) and inflammatory bowel
      disease. We have previously reported that IL-2 is necessary for optimal up
      regulation of CTLA-4, an inducible negative regulator of T cell activation. In
      this study, we have tested the hypothesis that reduced expression of CTLA-4 in IL
      2-deficient T cells contributes to the pathogenesis of disease in IL-2-deficient
      mice. Expression of CTLA-4 as a transgene completely prevented lymphoaccumulation
      and AHA in IL-2-deficient mice. The normalization of T cell numbers was due to
      inhibition of expansion of conventional CD4+CD25- T cells rather than to rescue
      of the numbers or function of CD4+CD25+ regulatory T cells, suggesting that CTLA
      4 expression on conventional T cells plays a role in maintaining normal T cell
      homeostasis. In addition, the inhibitory effect of the CTLA-4 transgene on T cell
      expansion was at least in part independent of CD28 expression. Our results
      suggest that deficient CTLA-4 expression on conventional T cells contributes to
      the pathophysiology of the lymphoproliferative disease and AHA in IL-2-deficient
      mice. Thus, restoring CTLA-4 expression in T cells may be an attractive strategy
      to control clinical autoimmune diseases in which CTLA-4 expression is reduced.

PMID- 15494489
TI  - The selective increase in caspase-3 expression in effector but not memory T cells
      allows susceptibility to apoptosis.
AB  - Caspases play a central role in T lymphocyte activation and death. We have
      demonstrated previously that caspase-3, an effector molecule for activation
      induced cell death (AICD), is processed following T cell activation in the
      absence of apoptosis. We report in this study that caspase-3 mRNA levels were
      selectively increased in peripheral T cells, following Ag receptor-mediated
      activation. The up-regulation of caspase-3 mRNA was confined to cells in the
      early phases of the cell cycle (G0/G1) and was independent of IL-2 signaling.
      This increase led to the renewal of procaspase-3 as evidenced by a 6-fold up
      regulation of the zymogen in nonapoptotic stimulated T cells. The increase of
      mRNA levels and of both the zymogen and the cleaved forms of caspase-3 was
      observed in in vivo stimulated Ag-specific effector, but not memory T cells,
      correlating with the enhanced susceptibility of effector T cells to AICD.
      Furthermore, we confirm that caspase-3 levels directly influence the sensitivity
      of activated T cells to apoptosis, as shown using T lymphocytes isolated from
      caspase-3 heterozygous and knockout mice. These findings indicate that the
      selective up-regulation of caspase-3 transcription is required to maintain the
      cytoplasmic levels of this protease, which control AICD and T cell homeostasis.

PMID- 15494490
TI  - The regulated expression of a diverse set of genes during thymocyte positive
      selection in vivo.
AB  - A signal initiated by the newly formed Ag receptor is integrated with
      microenvironmental cues during T cell development to ensure positive selection of
      CD4+CD8+ progenitors into functionally mature CD4+ or CD8+ T lymphocytes. During
      this transition, a survival program is initiated, TCR gene recombination ceases,
      cells migrate into a new thymic microenvironment, the responsiveness of the Ag
      receptor is tuned, and the cells commit to a specific T lineage. To determine
      potential regulators of these processes, we used mRNA microarray analysis to
      compare gene expression changes in CD4+CD8+ thymocytes from TCR transgenic mice
      that have received a TCR selection signal with those that had not received a
      signal. We found 129 genes with expression that changed significantly during
      positive selection, the majority of which were not previously appreciated. A
      large number of these changes were confirmed by real-time PCR or flow cytometry.
      We have combined our findings with gene changes reported in the literature to
      provide a comprehensive report of the genes regulated during positive selection,
      and we attempted to assign these genes to positive selection process categories.

PMID- 15494491
TI  - B7-H3 enhances tumor immunity in vivo by costimulating rapid clonal expansion of
      antigen-specific CD8+ cytolytic T cells.
AB  - B7-H3 is a B7 family molecule with T cell costimulatory function in vitro. The in
      vivo role of B7-H3 in the stimulation of tumor immunity is unclear. We report
      here that expression of B7-H3 by transfection of the mouse P815 tumor line
      enhances its immunogenicity, leading to the regression of tumors and
      amplification of a tumor-specific CD8+ CTL response in syngeneic mice. Tumor
      cells engineered to express B7-H3 elicit a rapid clonal expansion of P1A tumor Ag
      specific CD8+ CTL in lymphoid organs in vivo and acquire the ability to directly
      stimulate T cell growth, division, and development of cytolytic activity in
      vitro. Our results thus establish a role for B7-H3 in the costimulation of T cell
      immune responses in vivo.

PMID- 15494492
TI  - Functionally impaired HIV-specific CD8 T cells show high affinity TCR-ligand
      interactions.
AB  - We eventually isolated two different clonotypic CD8 T cell subsets recognizing an
      HIV Pol-derived epitope peptide (IPLTEEAEL) in association with HLA-B35 from a
      chronic HIV-infected patient. By kinetic analysis experiments, the subsets showed
      a >3-fold difference in half-lives for the HLA tetramer in complex with the Pol
      peptide. In functional assays in vitro and ex vivo, both subsets showed
      substantial functional avidity toward peptide-loaded cells. However, the high
      affinity subset did not show cytolytic activity, cytokine production, or
      proliferation activity toward HIV-infected cells, whereas the moderate affinity
      one showed potent activities. Furthermore, using ectopic expression of each of
      the TCR genes into primary human CD8 T cells, the CD8 T cells transduced with the
      high affinity TCR showed greater binding activity toward the tetramer and
      impaired cytotoxic activity toward HIV-infected cells, corroborating the results
      obtained with parental CD8 T cells. Taken together, these data indicate that
      impaired responsiveness of T cells toward HIV-infected cells can occur at the
      level of TCR-ligand interactions, providing us further insight into the immune
      evasion mechanisms by HIV.

PMID- 15494493
TI  - Prostaglandin E2-dependent enhancement of tissue inhibitors of metalloproteinases
      1 production limits dendritic cell migration through extracellular matrix.
AB  - Dendritic cell (DC) migration is crucial for the initiation of immune responses.
      The balance between metalloproteinases (MMP) and tissue inhibitors of
      metalloproteinases (TIMP) has been shown to modulate DC migration. PGE2, which is
      overproduced in a wide variety of human malignancies, has been implicated in MMP
      and TIMP regulation in various cells, including monocytes. In the present study,
      we hypothesized that tumor-derived PGE2 would affect DC migratory capacity
      through the extracellular matrix (ECM) by altering MMP and TIMP balance.
      Treatment of monocyte-derived immature DC with exogenous PGE2 induced TIMP-1
      secretion but not MMP-9 production and was correlated with reduced DC migration
      through ECM. Because recombinant TIMP-1 replicated PGE2 inhibition of DC
      migration while anti-TIMP-1 neutralizing Ab reversed it, we conclude that PGE2
      mediated induction of TIMP-1 was responsible for the reduced migration of PGE2
      treated DC. Similarly, DC cultured for 48 h in supernatants from cyclooxygenase-2
      overexpressing lung cancer cells that secrete high levels of PGE2, exhibited
      decreased migration through ECM. Finally, analysis of E prostanoid receptor
      expression and their selective inhibition revealed that the enhanced TIMP-1
      secretion in PGE2-treated DC was mediated predominantly by the E prostanoid
      receptor 2. These findings indicate that PGE2-dependent enhancement of TIMP-1
      production causes reduced migration of DC through ECM.

PMID- 15494494
TI  - Target antigens determine graft-versus-host disease phenotype.
AB  - Chronic graft-vs-host disease (cGVHD) is an increasingly frequent complication of
      allogeneic stem cell transplantation. Phenotypically, cGVHD differs from patient
      to patient; in particular, a subset of patients develops extensive cutaneous
      fibrosis. Similarly, graft-vs-host disease (GVHD) is distinct in inbred murine
      donor:recipient pairings, indicating a genetic component to disease phenotype.
      The B10.D2 -->BALB/c (H-2d) strain pairing uniquely recapitulates key pathologic
      features of fibrotic human cutaneous cGVHD. To distinguish whether this genetic
      component is due to differences in genes that modulate immune responses or to the
      specific Ags targeted, we asked whether skin-dominant cGVHD also develops in the
      B10 -->BALB.B (H-2b) and B10.BR -->BALB.K (H-2k) MHC-congenic pairings. Because
      each MHC haplotype presents different peptides and selects different T cell
      repertoires, GVHD in each donor:recipient pair undoubtedly targets different Ags.
      We found that, in contrast to BALB/c recipients, BALB.B mice never manifested
      skin disease while BALB.K mice developed a modified form of skin disease.
      Instead, BALB.B and BALB.K recipients developed systemic GVHD which was absent in
      BALB/c mice. Moreover, in (B10 x B10.D2)F1 -->(BALB.B x BALB/c)F1 H-2b/d
      transplants, recipients developed both cutaneous and systemic disease. Thus, the
      selection of immunodominant Ags determines the target and character of GVHD,
      providing insight into the genetic basis for different forms of GVHD.

PMID- 15494495
TI  - Evolution of transcriptional control of the IgH locus: characterization,
      expression, and function of TF12/HEB homologs of the catfish.
AB  - The transcriptional enhancer (Emu3') of the IgH locus of the channel catfish,
      Ictalurus punctatus, differs from enhancers of the mammalian IgH locus in terms
      of its position, structure, and function. Transcription factors binding to
      multiple octamer motifs and a single muE5 motif (an E-box site, consensus CANNTG)
      interact for its function. E-box binding transcription factors of the class I
      basic helix-loop-helix family were cloned from a catfish B cell cDNA library in
      this study, and homologs of TF12/HEB were identified as the most highly
      represented E-proteins. Two alternatively spliced forms of catfish TF12 (termed
      CFEB1 and -2) were identified and contained regions homologous to the basic helix
      loop-helix and activation domains of other vertebrate E-proteins. CFEB message is
      widely expressed, with CFEB1 message predominating over that of CFEB2. Both CFEB1
      and -2 strongly activated transcription from a muE5-dependent artificial
      promoter. In catfish B cells, CFEB1 and -2 also activated transcription from the
      core region of the catfish IgH enhancer (Emu3') in a manner dependent on the
      presence of the muE5 site. Both CFEB1 and -2 bound the muE5 motif, and formed
      both homo- and heterodimers. CFEB1 and -2 were weakly active or inactive (in a
      promoter-dependent fashion) in mammalian B-lineage cells. Although E-proteins
      have been highly conserved in vertebrate evolution, the present results indicate
      that, at the phylogenetic level of a teleost fish, the TF12/HEB homolog differs
      from that of mammals in terms of 1) its high level of expression and 2) the
      presence of isoforms generated by alternative RNA processing.

PMID- 15494496
TI  - Specificity-based negative selection of autoreactive B cells during memory
      formation.
AB  - Autoreactive B cells are not completely purged from the primary B cell
      repertoire, and whether they can be prevented from maturation into memory B cells
      has been uncertain. We show here that a population of B cells that dominates
      primary immune responses of BALB/c mice to influenza virus A/PR/8/34
      hemagglutinin (HA) are negatively selected in transgenic mice expressing PR8 HA
      as an abundant membrane-bound Ag (HACII mice). However, a separate population of
      B cells that contains precursors of memory B cells is activated by PR8 virus
      immunization and is subsequently negatively selected during the formation of the
      memory response. Negative selection of PR8 HA-specific B cells altered the
      specificity of the memory B cell response to a mutant virus containing a single
      amino acid substitution in a B cell epitope. Strikingly, this skewed reactivity
      resulted from an increase in the formation of memory B cells directed to non-self
      epitopes on the mutant virus, which increased 8-fold in HACII mice relative to
      nontransgenic mice and precisely compensated for the absence of autoreactive PR8
      HA-specific memory B cells. Negative selection of PR8 HA-specific B cells was a
      dominant process, since B cells from HACII mice could induce negative selection
      of PR8 HA-specific B cells from BALB/c mice. Lastly, HA-specific memory responses
      were unaffected by self-tolerance in another lineage of HA-transgenic mice (HA104
      mice), indicating that the amount and/or cell type in which self-Ags are
      expressed can determine their ability to prevent autoreactive memory B cell
      formation.

PMID- 15494497
TI  - CD4 phosphorylation partially reverses Nef down-regulation of CD4.
AB  - HIV Nef down-regulates CD4 from the cell surface in the absence of CD4
      phosphorylation, whereas PMA down-regulates CD4 through a phosphorylation
      dependent pathway. In this study we show that the down-regulation of CD4 in human
      Jurkat T cells expressing Nef was nearly complete (approximately 95%), whereas
      that induced by PMA was partial (approximately 40%). Unexpectedly, treating T
      cells expressing Nef with PMA restored the surface CD4 up to 35% of the steady
      state level. Both mutating the phosphorylation sites in the CD4 cytoplasmic tail
      (Ser408 and Ser415) and the use of a protein kinase C inhibitor,
      bisindolylmaleimide1, abolished the restoration of surface CD4, suggesting that
      the restoration required CD4 phosphorylation. CD4 and Nef could be cross-linked
      by a chemical cross-linker, 3,3-dithiobis[sulfosuccinimidyl-propionate], in
      control T cell membranes, but not in PMA-treated T cell membrane, suggesting that
      CD4 and Nef interacted with each other in T cells, and the phosphorylation
      disrupted the CD4-Nef interaction. We propose that this dissociation switches CD4
      internalization from the Nef-mediated, nearly complete down-regulation to a
      phosphorylation-dependent, partial down-regulation, resulting in a net gain of
      CD4 on the T cell surface.

PMID- 15494498
TI  - Altered Th1 cell differentiation programming by CIITA deficiency.
AB  - CD4 T cell differentiation is a complex process affected by many transcription
      factors interacting in a tightly regulated manner. We have previously shown that
      CIITA-deficient mouse Th1 cells expressed Th2-type cytokines, while IFN-gamma
      expression was normal. In this study, we show that CIITA-deficient Th1 cells
      contain three distinct populations: cells secreting IL-4 alone, IFN-gamma alone,
      and both IL-4 and IFN-gamma together. This novel phenotype is stable over
      multiple rounds of stimulation in the presence of Th1-inducing factors. CIITA
      deficient Th1 cells require TCR-mediated signaling to express Th2 cytokines, and
      this occurs with similar kinetics as wild-type Th2 cells. Both GATA-3 and IL-4
      appear to be required for CIITA-deficient Th1 cells to express Th2-type
      cytokines. Interestingly, however, CIITA-deficient Th1 cells can produce IL-4 in
      the absence of exogenous IL-4. Introducing either CIITA or antisense GATA-3
      during Th1 differentiation partially reduces Th2-type cytokine expression. With
      the exception of Th2-type cytokine expression, Th1 differentiation occurs
      normally in the absence of CIITA, as measured by expression of T-bet, IL
      12Rbeta2, IL-18Ralpha, and IFN-gamma. Therefore, CIITA plays a key role to
      repress Th2-type cytokine expression as naive CD4 T cells differentiate toward
      the Th1 lineage.

PMID- 15494499
TI  - Viral macrophage-inflammatory protein-II: a viral chemokine that differentially
      affects adaptive mucosal immunity compared with its mammalian counterparts.
AB  - Chemokines play a profound role in leukocyte trafficking and the development of
      adaptive immune responses. Perhaps due to their importance in host defense,
      viruses have adopted many of the hallmarks displayed by chemokines. In
      particular, viral MIP-II (vMIP-II) is a human chemokine homologue that is encoded
      by human herpes virus 8. vMIP-II is angiogenic, selectively chemotactic for Th2
      lymphocytes, and a homologue of human I-309 and mouse TCA-3, which also
      differentially attracts Th2 cells. To better understand the effect of viral
      chemokines on mucosal immunity, we compared the affects of vMIP-II, I-309, and
      TCA-3 on cellular and humoral immune responses after nasal immunization with OVA.
      These CCR8 ligands significantly enhanced Ag-specific serum and mucosal Abs
      through increasing Th2 cytokine secretion by CD4+ T cells. These alterations in
      adaptive humoral and cellular responses were preceded (12 h after immunization)
      by an increase in CD4+ T and B cells in nasal tracts with decreases of these
      leukocyte populations in the lung. Interestingly, vMIP-II increased neutrophil
      infiltration in the lung and Ag-specific IL-10-secreting CD4+ T cells after
      immunization. Although I-309 increased the number of CD28-, CD40L-, and CD30
      positive, Ag-stimulated naive CD4+ T cells, vMIP-II and TCA-3 decreased the
      number of CD28-, CD40L-, and CD30-positive, resting naive CD4+ T cells. Taken
      together, these studies suggest that CCR8 ligands direct host Th2 responses, and
      vMIP-II up-regulates IL-10 responses and limits costimulatory molecule expression
      to mitigate host immunity.

PMID- 15494500
TI  - Delineation of signals required for thymocyte positive selection.
AB  - Peptide/MHC complexes capable of inducing positive selection in mouse fetal
      thymic organ cultures fail to do so in suspension culture. Furthermore, this type
      of culture does not promote initial stages of differentiation, such as coreceptor
      down-modulation, unless peptides used for stimulation have (at least) weak
      agonist activity. We show in this study that signals provided in suspension
      culture by nonagonist peptide/MHC complexes on the surface of macrophages, even
      though apparently silent, are sufficient to promote complete phenotypic
      differentiation when CD4+CD8+ thymocytes are subsequently placed in a proper
      anatomical setting. Furthermore, the synergistic actions of suboptimal
      concentrations of phorbol esters and nonagonist peptide/MHC complexes can make
      the initial stages of positive selection visible, without converting maturation
      into negative selection. Thus, the correlation between efficiency of positive
      selection and the degree of coreceptor down-modulation on CD4+CD8+ thymocytes is
      not linear. Furthermore, these results suggest that the unique role of thymic
      stromal cells in positive selection is related not to presentation of self
      peptide/MHC complexes, but most likely to another ligand.

PMID- 15494502
TI  - Germline transcription and switch recombination of a transgene containing the
      entire H chain constant region locus: effect of a mutation in a STAT6 binding
      site in the gamma 1 promoter.
AB  - The switch (S) in H chain class is preceded by germline transcription and then
      mediated by a DNA recombination event. One of the impediments toward
      understanding the mechanism is the lack of a system in which a recombinant DNA
      molecule undergoes cytokine-regulated class S recombination. To study class S
      recombination, we used transgenic mice with a 230-kb bacterial artificial
      chromosome that included a rearranged VDJ gene and the entire murine H chain
      constant region locus. We found that both germline transcription and S
      recombination to the transgenic gamma1 H chain gene were regulated by IL-4 like
      that of the endogenous genes. In mice with two or more copies of the H chain
      locus transgene, both germline transcripts and S recombination took place at
      levels comparable to those from the endogenous loci. We also prepared a version
      of the transgene with a 4-bp mutation in a STAT6 binding site in the gamma1
      promoter region. On the average, this mutation reduced germline transcription by
      80%, but did not change the amount of S recombination in vitro. Among both the
      wild-type and mutant transgenes, we found no significant correlation between the
      amount of germline transcripts and the amount of S recombination. We infer that
      the physiologic level of germline transcription of the gamma1 gene is in excess
      over the amount required for efficient S recombination.

PMID- 15494503
TI  - Complement inactivation by recombinant human C3 derivatives.
AB  - From the implications of the complement system in a large number of diseases, an
      urgent need for therapeutics effecting reduced complement activity in vivo has
      emerged. In this study we report the design of a novel class of enzymes of human
      origin that obliterate functional complement by a noninhibitory, catalytic
      mechanism. Combining the framework of human C3 and the enzymatic mechanism of
      cobra venom factor, a nontoxic snake venom protein, we established molecules
      capable of forming stable C3 convertase complexes. Although the half-life of
      naturally occurring C3 convertase complexes ranges between 1 and 2 min, these
      complexes exhibit a half-life of up to several hours. Because the overall
      identity to human C3 could be extended to >90%, the novel C3 derivatives can be
      assumed to exhibit low immunogenicity and, therefore, represent promising
      candidates for therapeutic reduction of complement activity in vivo.

PMID- 15494501
TI  - Differential regulation of Th1/Th2 cytokine responses by placental protein 14.
AB  - The potency of TCR signaling during primary CD4+ T cell activation influences
      initial cytokine expression patterns and subsequent polarization toward either
      Th1 or Th2 subsets. In this study, we demonstrate that the T cell inhibitor
      placental protein 14 (PP14; glycodelin) preferentially inhibits Th1 cytokine
      responses and chemokine expression when present during ex vivo priming of CD4+ T
      cells. PP14 synergizes with exogenously added IL-4 in skewing T cell responses.
      Significantly, PP14 impairs the down-regulation of GATA-3 transcriptional
      regulator expression that normally accompanies T cell activation, which is a
      prerequisite for Th1 development. Taken together, these data document for the
      first time the ability of PP14 to skew Th responses.

PMID- 15494504
TI  - Roles of TNF receptor-associated factor 3 in signaling to B lymphocytes by
      carboxyl-terminal activating regions 1 and 2 of the EBV-encoded oncoprotein
      latent membrane protein 1.
AB  - TNFR-associated factor (TRAF)3, an adaptor protein that binds the cytoplasmic
      domains of both CD40 and the EBV-encoded oncoprotein latent membrane protein
      (LMP)1, is required for positive signaling by LMP1 but not CD40 in B lymphocytes.
      The present study further investigated how TRAF3 participates in LMP1 signaling.
      We found that TRAF3 mediates signaling both through direct interactions with the
      C-terminal activating region (CTAR)1 of LMP1 and through indirect interactions
      with the CTAR2 region of LMP1 in mouse B cells. Notably, our results demonstrated
      that the CTAR2 region appears to inhibit the recruitment of TRAF1 and TRAF2 to
      membrane rafts by the CTAR1 region. Additionally, the absence of TRAF2 in B cells
      resulted in only a modest reduction in CTAR1-mediated signals and no detectable
      effect on CTAR2-mediated signals. CTAR1 and CTAR2 cooperated to achieve the
      robust signaling activity of LMP1 when recruited to the same membrane
      microdomains in B cells. Interestingly, TRAF3 deficiency completely abrogated the
      cooperation between CTAR1 and CTAR2, supporting the hypothesis that TRAF3
      participates in the physical interaction between CTAR1 and CTAR2 of LMP1.
      Together, our findings highlight the central importance of TRAF3 in LMP1-mediated
      signaling, which is critical for EBV persistent infection and EBV-associated
      pathogenesis.

PMID- 15494505
TI  - B lymphocyte-induced maturation protein (Blimp)-1, IFN regulatory factor (IRF)-1,
      and IRF-2 can bind to the same regulatory sites.
AB  - The transcriptional repressor B lymphocyte-induced maturation protein-1 (Blimp-1)
      is expressed in some differentiated cells and is required for terminal
      differentiation of B cells. To facilitate identification of Blimp-1 target genes,
      we have determined the optimal DNA recognition sequence for Blimp-1. The
      consensus is very similar to a subset of sites recognized by IFN regulatory
      factors (IRFs) that contain the sequence GAAAG. By binding competition and
      determination of equilibrium dissociation constants, we show that Blimp-1, IRF-1,
      and IRF-2 have similar binding affinities for functionally important regulatory
      sites containing this sequence. However, Blimp-1 does not bind to all IRF sites,
      and specifically does not recognize IRF-4/PU.1 or IRF-8 sites lacking the GAAAG
      sequence. Chromatin immunoprecipitation studies showed that Blimp-1, IRF-1, and
      IRF-2 all bind the IFN-beta promoter in vivo, as predicted by the in vitro
      binding parameters, and in cotransfections Blimp-1 inhibits IRF-1-dependent
      activation of the IFN-beta promoter. Thus, our data suggest that Blimp-1 competes
      in vivo with a subset of IRF proteins and help predict the sites and IRF family
      members that may be affected.

PMID- 15494506
TI  - The interaction between GATA proteins and activator protein-1 promotes the
      transcription of IL-13 in mast cells.
AB  - IL-13 is considered to be a key modulator in the pathogenesis of Th2-induced
      allergic inflammation, although little is known about the regulation of IL-13
      transcription in mast cells. In T cells, involvement of GATA-3 in cell type
      specific expression of the IL-13 gene has been reported. However, the mechanisms
      that induce rapid transactivation of the IL-13 gene in response to various types
      of stimulation have hitherto remained unknown. In this report, we describe our
      investigation of the promoter region necessary for IL-13 transcription; we have
      found that both AP-1 and GATA proteins are indispensable for IL-13 transcription
      in mouse mast cells. In our investigation, we focused on the functional
      interaction between GATA and AP-1 in the IL-13 promoter context. Transfection
      experiments have revealed that GATA-1 and GATA-2 proteins are able to associate
      with AP-1 proteins. We have also shown that overexpression of GATA-1 induced
      excess AP-1 binding to the IL-13 promoter as well as a significant increase in IL
      13 production in mast cells. The results of the present study have shown that
      direct interaction between AP-1 and GATA proteins plays an important role in IL
      13 transcription in mast cells.

PMID- 15494507
TI  - Shark Ig light chain junctions are as diverse as in heavy chains.
AB  - We have characterized a small family of four genes encoding one of the three
      nurse shark Ig L chain isotypes, called NS5. All NS5 cDNA sequences are encoded
      by three loci, of which two are organized as conventional clusters, each
      consisting of a V and J gene segment that can recombine and one C region exon;
      the third contains a germline-joined VJ in-frame and the fourth locus is a
      pseudogene. This is the second nurse shark L chain type where both germline
      joined and split V-J organizations have been found. Since there are only two
      rearranging Ig loci, it was possible for the first time to examine junctional
      diversity in defined fish Ig genes, comparing productive vs nonproductive
      rearrangements. N region addition was found to be considerably more extensive in
      length and in frequency than any other vertebrate L chain so far reported and
      rivals that in H chain. We put forth the speculation that the unprecedented
      efficiency of N region addition (87-93% of NS5 sequences) may be a result not
      only of simultaneous H and L chain rearrangement in the shark but also of
      processing events that afford greater accessibility of the V or J gene coding
      ends to terminal deoxynucleotidyltransferase.

PMID- 15494509
TI  - Exclusion and inclusion of TCR alpha proteins during T cell development in TCR
      transgenic and normal mice.
AB  - Allelic exclusion of immune receptor genes (and molecules) is incompletely
      understood. With regard to TCRalphabeta lineage T cells, exclusion at the tcr-b,
      but not tcr-a, locus seems to be strictly controlled at the locus rearrangement
      level. Consequently, while nearly all developing TCRalphabeta thymocytes express
      a single TCRbeta protein, many thymocytes rearrange and express two different
      TCRalpha chains and, thus, display two alphabetaTCRs on the cell surface. Of
      interest, the number of such dual TCR-expressing cells is appreciably lower among
      the mature T cells. To understand the details of TCR chain regulation at various
      stages of T cell development, we analyzed TCR expression in mice transgenic for
      two rearranged alphabetaTCR. We discovered that in such TCR double-transgenic
      (TCRdTg) mice peripheral T cells were functionally monospecific. Molecularly,
      this monospecificity was due to TCRalpha exclusion: one transgenic TCRalpha
      protein was selectively down-regulated from the thymocyte and T cell surface. In
      searching for the mechanism(s) governing this selective TCRalpha down-regulation,
      we present evidence for the role of protein tyrosine kinase signaling and
      coreceptor involvement. This mechanism may be operating in normal thymocytes.

PMID- 15494508
TI  - NF-kappa B regulates expression of the MHC class I-related chain A gene in
      activated T lymphocytes.
AB  - MHC class I-related chain A gene (MICA) is a stress-regulated, HLA-related
      molecule which exhibits a restricted pattern of expression. MICA protein is up
      regulated on different tumor cells, and is recognized by the lectin-like NKG2D
      molecule expressed by cytotoxic gammadelta T lymphocytes, CD8+ alphabeta T
      lymphocytes, and NK cells. Although MICA is not expressed on resting lymphocytes,
      we demonstrated that it is induced on activated T cells. Because NF-kappaB is
      actively involved in T cell activation, and is constitutively activated in many
      tumors, here we investigated whether NF-kappaB may modulate MICA expression.
      Treatment with the NF-kappaB inhibitor sulfasalazine (Sz) resulted in a dose
      dependent inhibition of MICA expression in anti-CD3- and anti-CD28/PMA-activated
      T lymphocytes, as assessed by Western blot and RT-PCR analysis. Moreover, Sz also
      down-regulated MICA expression on epithelial tumor HeLa cells. MICA expression
      was accompanied by a Sz-sensitive IkappaBalpha degradation. EMSA with nuclear
      extracts from anti-CD3- and anti-CD28/PMA-stimulated T lymphocytes demonstrated
      the binding of a potential NF-kappaB family transcription factor to a MICA gene
      intron 1-derived oligonucleotide that contains a putative kappaB binding site.
      Supershift assays demonstrated the presence of p65(RelA)/p50 heterodimers and
      p50/p50 homodimers in the NF-kappaB complexes bound to the kappaB-MICA
      oligonucleotide. Transient transfection of HeLa cells with p65(RelA) up-regulated
      MICA expression, as assessed by Western blot and flow cytometry analysis. Hence,
      we conclude that NF-kappaB regulates MICA expression on activated T lymphocytes
      and HeLa tumor cells, by binding to a specific sequence in the long intron 1 of
      the MICA gene. This constitutes the first description of a transcription factor
      that regulates MICA gene expression.

PMID- 15494510
TI  - The B lymphocyte adaptor molecule of 32 kilodaltons (Bam32) regulates B cell
      antigen receptor internalization.
AB  - The B lymphocyte adaptor molecule of 32 kDa (Bam32) is an adaptor that plays an
      indispensable role in BCR signaling. In this study, we found that upon BCR
      ligation, Bam32 is recruited to the plasma membrane where it associates with BCR
      complexes and redistributes and internalizes with BCRs. BCR ligation induced
      colocalization of Bam32 with lipid rafts, clathrin, and actin filaments. An
      inhibitor of Src family protein tyrosine kinases (PTKs) blocked both BCR-induced
      tyrosine phosphorylation of Bam32 and BCR internalization. Moreover, BCR
      internalization is impaired in Bam32-/- and Lyn-/- cells, and expression of Bam32
      with a mutation of its tyrosine phosphorylation site (Y139F) inhibited BCR
      internalization. These data suggest that Bam32 functions downstream of Src family
      PTKs to regulate BCR internalization. Bam32 deficiency does not affect tyrosine
      phosphorylation of clathrin or the association of clathrin with lipid rafts upon
      BCR cross-linking. However, BCR-induced actin polymerization is impaired in Bam32
      /- cells. Collectively, these findings indicate a novel role of Bam32 in
      connecting Src family PTKs to BCR internalization by an actin-dependent
      mechanism.

PMID- 15494514
TI  - Dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin
      mediates binding and internalization of Aspergillus fumigatus conidia by
      dendritic cells and macrophages.
AB  - Aspergillus fumigatus is responsible for a large percentage of nosocomial
      opportunistic fungal infections in immunocompromised hosts, especially during
      cytotoxic chemotherapy and after bone marrow transplantation, and is currently a
      major direct cause of death in leukemia patients. Dendritic cell-specific ICAM-3
      grabbing nonintegrin (DC-SIGN) is a type II C-type lectin that functions as an
      adhesion receptor and is used by viral and bacterial pathogens to gain access to
      human DC. We report that DC-SIGN specifically interacts with clinical isolates of
      A. fumigatus. DC-SIGN-dependent binding of A. fumigatus conidia can be
      demonstrated with stable transfectants and monocyte-derived DC and is inhibited
      by anti-DC-SIGN Abs. Binding and internalization of A. fumigatus conidia
      correlates with DC-SIGN cell surface expression levels and is abolished in the
      presence of A. fumigatus-derived cell wall galactomannans. The clinical relevance
      of this interaction is emphasized by the presence of DC-SIGN in lung DC and
      alveolar macrophages, and further illustrated by the DC-SIGN-dependent attachment
      of A. fumigatus conidia to the cell membrane of IL-4-treated monocyte-derived
      macrophages. Our results suggest the involvement of DC-SIGN in the initial stages
      of pulmonary infection as well as in fungal spreading during invasive
      aspergillosis.

PMID- 15494511
TI  - Conformational restraints and flexibility of 14-meric peptides in complex with
      HLA-B*3501.
AB  - Human HLA-B*3501 binds an antigenic peptide of 14-aa length derived from an
      alternative reading frame of M-CSF with high affinity. Due to its extraordinary
      length, the exact HLA binding mode was unpredictable. The crystal structure of
      HLA-B*3501 at 1.5 A shows that the N and C termini of the peptide are embedded in
      the A and F pockets, respectively, similar to a peptide of normal length. The
      central part of the 14-meric peptide bulges flexibly out of the groove. Two
      variants of the alternative reading frame of M-CSF peptide substituted at P2 or
      P2 and P9 with Ala display weak or no T cell activation. Their structure differs
      mainly in flexibility and conformation from the agonistic peptide. Moreover, the
      variants induce subtle changes of MHC alpha-helical regions implicated as
      critical for TCR contact. The TCR specifically recognizing this peptide/MHC
      complex exhibits CDR3 length within the normal range, suggesting major
      conformational adaptations of this receptor upon peptide/MHC binding. Thus, the
      potential antigenic repertoire recognizable by CTLs is larger than currently
      thought.

PMID- 15494512
TI  - The actin cytoskeleton controls the efficiency of killer Ig-like receptor
      accumulation at inhibitory NK cell immune synapses.
AB  - Killer cell Ig-like receptors (KIRs) are MHC class I-specific receptors expressed
      in NK and T lymphocytes. KIR antagonism of activation signals occurs at the
      immune synapse between the effector and target cells. The processes that regulate
      clustering of KIR are not well defined. We have expressed KIR-GFP receptor
      chimeras in two human NK-like lines, YTS and NK92. In this study, we show that
      the frequency of KIR enrichment at the synapse was decreased for a KIR that lacks
      a portion of the cytoplasmic tail. Strikingly, blocking actin polymerization with
      a high dose of cytochalasin D also substantially decreased clustering of KIR as
      well as KIR-induced clustering of HLA-C-GFP in target cells. However, the effect
      of inhibiting actin polymerization was only clearly evident at the earlier time
      points after cell mixing, and eventually clustering of KIR and HLA-C occurred
      independently of actin remodeling. Although treatment with anti-LFA-1 also
      decreased conjugate formation, the frequency of KIR clustering remained normal
      within the population of conjugates that did form, suggesting that the effect of
      cytochalasin D is not solely through LFA-1. Collectively, these data suggest that
      the actin cytoskeleton and the cytoplasmic tail of KIR regulate the efficiency by
      which KIR accumulates at inhibitory NK cell synapses.

PMID- 15494513
TI  - The IL-27 receptor (WSX-1) is an inhibitor of innate and adaptive elements of
      type 2 immunity.
AB  - Although previous studies have investigated the role of IL-27/WSX-1 interactions
      in the regulation of Th1 responses, little is known about their role in
      regulating Th2-type responses. Studies presented in this work identify a direct
      role for IL-27/WSX-1 interactions in the negative regulation of type 2 responses
      independent of effects on type 1 cytokines. WSX-1-/- mice infected with the
      gastrointestinal helminth Trichuris muris displayed accelerated expulsion of
      parasites and the development of exaggerated goblet cell hyperplasia and
      mastocytosis in the gut due to increased production of Th2 cytokines. Enhanced
      mast cell activity in the absence of WSX-1 was consistent with the ability of
      wild-type mast cells to express this receptor. In addition, IL-27 directly
      suppressed CD4+ T cell proliferation and Th2 cytokine production. Together, these
      studies identify a novel role for IL-27/WSX-1 in limiting innate and adaptive
      components of type 2 immunity at mucosal sites.

PMID- 15494515
TI  - Cross-presentation of Listeria-derived CD8 T cell epitopes requires unstable
      bacterial translation products.
AB  - Presentation of bacteria-derived CD8 T cell epitopes by dendritic cells (DC)
      requires either their direct infection or that DC acquire and cross-present Ags
      from other infected cells. We found that cross-presentation of Listeria
      monocytogenes-derived CD8 T cell epitopes was much stronger than direct Ag
      presentation by infected murine DC. Cross-presentation of Listeria-derived CD8 T
      cell epitopes showed unique physiological requirements. It was dependent upon the
      delivery of unstable bacterial translation products by infected, but still
      viable, Ag donor cells. Cross-presentation was enhanced both when unstable
      translation products in infected Ag donor cells were protected from proteasomal
      degradation and when the production of misfolded bacterial proteins was
      increased. The requirement of unstable translation products for cross
      presentation may represent a novel pathway that functions to focus the CD8 T cell
      response toward epitopes derived from newly synthesized proteins.

PMID- 15494516
TI  - Reduced apoptosis and ameliorated listeriosis in TRAIL-null mice.
AB  - Listeriosis is an infectious disease caused by the bacterium Listeria
      monocytogenes. Although it is well recognized that apoptosis plays a critical
      role in the pathogenesis of the disease, the molecular mechanisms of cell death
      in listeriosis remain to be established. We report in this study that mice
      deficient in TRAIL were partially resistant to primary listeriosis, and blocking
      TRAIL with a soluble death receptor 5 markedly ameliorated the disease. The
      numbers of Listeria in the liver and spleen of TRAIL+/+ mice were 10-100 times
      greater than those in TRAIL-/- mice following primary Listeria infection. This
      was accompanied by a significant increase in the survival rate of TRAIL-/- mice.
      Lymphoid and myeloid cell death was significantly inhibited in TRAIL-/- mice,
      which led to marked enlargement of the spleen. These results establish a critical
      role for TRAIL in apoptosis during listeriosis.

PMID- 15494517
TI  - Pseudomonas aeruginosa flagellin and alginate elicit very distinct gene
      expression patterns in airway epithelial cells: implications for cystic fibrosis
      disease.
AB  - Infection with the opportunistic pathogen Pseudomonas aeruginosa remains a major
      health concern. Two P. aeruginosa phenotypes relevant in human disease include
      motility and mucoidy. Motility is characterized by the presence of flagella and
      is essential in the establishment of acute infections, while mucoidy, defined by
      the production of the exopolysaccharide alginate, is critical in the development
      of chronic infections, such as the infections seen in cystic fibrosis patients.
      Indeed, chronic infection of the lung by mucoid P. aeruginosa is a major cause of
      morbidity and mortality in cystic fibrosis patients. We have used Calu-3 human
      airway epithelial cells to investigate global responses to infection with motile
      and mucoid P. aeruginosa. The response of airway epithelial cells to exposure to
      P. aeruginosa motile strains is characterized by a specific increase in gene
      expression in pathways controlling inflammation and host defense. By contrast,
      the response of airway epithelia to the stimuli presented by mucoid P. aeruginosa
      is not proinflammatory and, hence, may not be conducive to the effective
      elimination of the pathogen. The pattern of gene expression directed by
      flagellin, but not alginate, includes innate host defense genes, proinflammatory
      cytokines, and chemokines. By contrast, infection with alginate-producing P.
      aeruginosa results in an overall attenuation of host responses and an
      antiapoptotic effect.

PMID- 15494518
TI  - Human monoclonal antibodies to Pseudomonas aeruginosa alginate that protect
      against infection by both mucoid and nonmucoid strains.
AB  - Two fully human mAbs specific for epitopes dependent on intact carboxylate groups
      on the C6 carbon of the mannuronic acid components of Pseudomonas aeruginosa
      alginate were found to promote phagocytic killing of both mucoid and nonmucoid
      strains as well as protection against both types of strains in a mouse model of
      acute pneumonia. The specificity of the mAbs for alginate was determined by ELISA
      and killing assays. Some strains of P. aeruginosa did not make detectable
      alginate in vitro, but in vivo protection against lethal pneumonia was obtained
      and shown to be due to rapid induction of expression of alginate in the murine
      lung. No protection against strains genetically unable to make alginate was
      achieved. These mAbs have potential to be passive therapeutic reagents for all
      strains of P. aeruginosa and the results document that alginate is a target for
      the proper type of protective Ab even when expressed at low levels on
      phenotypically nonmucoid strains.

PMID- 15494519
TI  - Duration of infection and antigen display have minimal influence on the kinetics
      of the CD4+ T cell response to Listeria monocytogenes infection.
AB  - The T cell response to infection consists of clonal expansion of effector cells,
      followed by contraction to memory levels. It was previously thought that the
      duration of infection determines the magnitude and kinetics of the T cell
      response. However, recent analysis revealed that transition between the expansion
      and contraction phases of the Ag-specific CD8+ T cell response is not affected by
      experimental manipulation in the duration of infection or Ag display. We studied
      whether the duration of infection and Ag display influenced the kinetics of the
      Ag-specific CD4+ T cell response to Listeria monocytogenes (LM) infection. We
      found that truncating infection and Ag display with antibiotic treatment as early
      as 24 h postinfection had minimal impact on the expansion or contraction of CD4+
      T cells; however, the magnitudes of the Ag-specific CD4+ and CD8+ T cell
      responses were differentially affected by the timing of antibiotic treatment.
      Treatment of LM-infected mice with antibiotics at 24 h postinfection did not
      prevent generation of detectable CD4+ and CD8+ memory T cells at 28 days after
      infection, vigorous secondary expansion of these memory T cells, or protection
      against a subsequent LM challenge. These results demonstrate that events within
      the first few days of infection stimulate CD4+ and CD8+ T cell responses that are
      capable of carrying out the full program of expansion and contraction to
      functional memory, independently of prolonged infection or Ag display.

PMID- 15494520
TI  - Expression of functional TLR4 confers proinflammatory responsiveness to
      Trypanosoma cruzi glycoinositolphospholipids and higher resistance to infection
      with T. cruzi.
AB  - TLRs function as pattern recognition receptors in mammals and play an essential
      role in the recognition of microbial components. We found that the injection of
      glycoinositolphospholipids (GIPLs) from Trypanosoma cruzi into the peritoneal
      cavity of mice induced neutrophil recruitment in a TLR4-dependent manner: the
      injection of GIPL in the TLR4-deficient strain of mice (C57BL/10ScCr) caused no
      inflammatory response. In contrast, in TLR2 knockout mice, neutrophil
      chemoattraction did not differ significantly from that seen in wild-type
      controls. GIPL-induced neutrophil attraction and MIP-2 production were also
      severely affected in TLR4-mutant C3H/HeJ mice. The role of TLR4 was confirmed in
      vitro by testing genetically engineered mutants derived from TLR2-deficient
      Chinese hamster ovary (CHO)-K1 fibroblasts that were transfected with CD14
      (CHO/CD14). Wild-type CHO/CD14 cells express the hamster TLR4 molecule and the
      mutant line, in addition, expresses a nonfunctional form of MD-2. In comparison
      to wild-type cells, mutant CHO/CD14 cells failed to respond to GIPLs, indicating
      a necessity for a functional TLR4/MD-2 complex in GIPL-induced NF-kappaB
      activation. Finally, we found that TLR4-mutant mice were hypersusceptible to T.
      cruzi infection, as evidenced by a higher parasitemia and earlier mortality.
      These results demonstrate that natural resistance to T. cruzi is TLR4 dependent,
      most likely due to TLR4 recognition of their GIPLs.

PMID- 15494521
TI  - Rac1 contributes to maximal activation of STAT1 and STAT3 in IFN-gamma-stimulated
      rat astrocytes.
AB  - Rac1 GTPase is implicated as a signaling mediator in various cellular events. In
      this study, we show that Rac1 contributes to IFN-gamma-induced inflammatory
      responses in rat astrocytes. We revealed that IFN-gamma rapidly stimulated
      activation of Rac1 in C6 astroglioma cells by investigating GST-PAK-PBD-binding
      ability. We also found that Rac1 deficiency led to attenuation of IFN-gamma
      responsive transcriptional responses. Compared with levels in control cells, IFN
      gamma-induced IFN-gamma-activated sequence promoter activity was markedly reduced
      in both C6 astroglioma cells and primary astrocytes expressing RacN17, a well
      characterized Rac1-negative mutant. The expression of several IFN-gamma
      responsive genes, such as MCP-1 and ICAM-1, was also reduced in cells expressing
      RacN17. Consistent with these observations, IFN-gamma-induced phosphorylation of
      STAT1 and STAT3 was lower in C6 cells expressing RacN17 (referred to as C6
      RacN17) than in control cells. However, there was no difference in expression
      level of IFN-gammaRalpha subunit and IFN-gamma-induced phosphorylation of JAK1
      between C6 control and C6-RacN17 cells. Interestingly, Rac1 appeared to associate
      with IFN-gammaRalpha and augment the interaction of IFN-gammaR with either STAT1
      or STAT3 in response to IFN-gamma. Taken together, we suggest that Rac1 may serve
      as an auxiliary mediator of IFN-gamma-signaling, at least at the level of STAT
      activation, thus contributing to maximal activation of IFN-gamma-responsive
      inflammatory signaling in rat astrocytes.

PMID- 15494522
TI  - N-terminal residues of the chemotaxis inhibitory protein of Staphylococcus aureus
      are essential for blocking formylated peptide receptor but not C5a receptor.
AB  - Staphylococcus aureus excretes a factor that specifically and simultaneously acts
      on the C5aR and the formylated peptide receptor (FPR). This chemotaxis inhibitory
      protein of S. aureus (CHIPS) blocks C5a- and fMLP-induced phagocyte activation
      and chemotaxis. Monoclonal anti-CHIPS Abs inhibit CHIPS activity against one
      receptor completely without affecting the other receptor, indicating that two
      distinct sites are responsible for both actions. A CHIPS-derived N-terminal 6 aa
      peptide is capable of mimicking the anti-FPR properties of CHIPS but has no
      effect on the C5aR. Synthetic peptides in which the first 6 aa are substituted
      individually for all other naturally occurring amino acids show that the first
      and third residue play an important role in blocking the FPR. Using an
      Escherichia coli expression system, we created mutant CHIPS proteins in which
      these amino acids are substituted. These mutant proteins have impaired or absent
      FPR- but still an intact C5aR-blocking activity, indicating that the loss of the
      FPR-blocking activity is not caused by any structural impairment. This identifies
      the first and third amino acid, both a phenylalanine, to be essential for CHIPS
      blocking the fMLP-induced activation of phagocytes. The unique properties of
      CHIPS to specifically inhibit the FPR with high affinity (kd=35.4 +/- 7.7 nM)
      could be an important new tool to further stimulate the fundamental research on
      the mechanisms underlying the FPR and its role in disease processes.

PMID- 15494523
TI  - Polymorphonuclear cell transmigration induced by Pseudomonas aeruginosa requires
      the eicosanoid hepoxilin A3.
AB  - Lung inflammation resulting from bacterial infection of the respiratory mucosal
      surface in diseases such as cystic fibrosis and pneumonia contributes
      significantly to the pathology. A major consequence of the inflammatory response
      is the recruitment and accumulation of polymorphonuclear cells (PMNs) at the
      infection site. It is currently unclear what bacterial factors trigger this
      response and exactly how PMNs are directed across the epithelial barrier to the
      airway lumen. An in vitro model consisting of human PMNs and alveolar epithelial
      cells (A549) grown on inverted Transwell filters was used to determine whether
      bacteria are capable of inducing PMN migration across these epithelial barriers.
      A variety of lung pathogenic bacteria, including Klebsiella pneumoniae,
      Escherichia coli, and Pseudomonas aeruginosa are indeed capable of inducing PMN
      migration across A549 monolayers. This phenomenon is not mediated by LPS, but
      requires live bacteria infecting the apical surface. Bacterial interaction with
      the apical surface of A549 monolayers results in activation of epithelial
      responses, including the phosphorylation of ERK1/2 and secretion of the PMN
      chemokine IL-8. However, secretion of IL-8 in response to bacterial infection is
      neither necessary nor sufficient to mediate PMN transepithelial migration.
      Instead, PMN transepithelial migration is mediated by the eicosanoid hepoxilin
      A3, which is a PMN chemoattractant secreted by A549 cells in response to
      bacterial infection in a protein kinase C-dependent manner. These data suggest
      that bacterial-induced hepoxilin A3 secretion may represent a previously
      unrecognized inflammatory mechanism occurring within the lung epithelium during
      bacterial infections.

PMID- 15494524
TI  - A new pharmacological effect of salicylates: inhibition of NFAT-dependent
      transcription.
AB  - The anti-inflammatory effects of salicylates, originally attributed to inhibition
      of cyclooxygenase activity, are currently known to involve additional mechanisms.
      In this study we investigated the possible modulation by salicylates of NFAT
      mediated transcription in lymphocytic and monocytic cell lines. RNase protection
      assays showed that 2-acetoxy-4-trifluoromethylbenzoic acid (triflusal) inhibited,
      in a dose-dependent manner, mRNA expression of several cytokine genes, most of
      which are NFAT-regulated and cyclosporin A (CsA)-sensitive. In Jurkat cells, the
      expression of IL-3, GM-CSF, TNF-alpha, TGF-beta1, IL-2, lymphotactin, MIP-1alpha,
      and MIP-1beta was inhibited to different extents. In THP-1 cells, inhibition of
      the expression of M-CSF, G-CSF, stem cell factor, IFN-gamma, TNF-alpha, TGF
      beta1, lymphotoxin-beta1, MIP-1alpha, MIP-1beta, and IL-8 was observed. Sodium
      salicylate and aspirin only showed significant effects at 5 mM. The
      transcriptional activity of two genes that contain NFAT sites, a GM-CSF full
      promoter and a T cell-specific enhancer from the IL-3 locus, was also inhibited
      by salicylates. Transactivation experiments performed with several NFAT-dependent
      and AP-1-dependent reporter genes showed that triflusal strongly inhibited NFAT
      dependent transcription at concentrations as low as 0.25 mM. Sodium salicylate
      and aspirin were less potent. The triflusal inhibitory effect was reversible and
      synergized with suboptimal doses of CsA. Experiments to address the mechanism of
      action of salicylates in the NFAT activation cascade disclosed a mechanism
      different from that of CsA, because salicylates inhibited DNA-binding and NFAT
      mediated transactivation without affecting phosphorylation or subcellular
      localization of NFAT. In summary, these data describe a new pharmacological
      effect of salicylates as inhibitors of NFAT-dependent transcription.

PMID- 15494525
TI  - Protein kinase C delta is required for p47phox phosphorylation and translocation
      in activated human monocytes.
AB  - Our laboratory is interested in understanding the regulation of NADPH oxidase
      activity in human monocyte/macrophages. Protein kinase C (PKC) is reported to be
      involved in regulating the phosphorylation of NADPH oxidase components in human
      neutrophils; however, the regulatory roles of specific isoforms of PKC in
      phosphorylating particular oxidase components have not been determined. In this
      study calphostin C, an inhibitor for both novel PKC (including PKCdelta, 
      epsilon, -theta;, and -eta) and conventional PKC (including PKCalpha and -beta),
      inhibited both phosphorylation and translocation of p47phox, an essential
      component of the monocyte NADPH oxidase. In contrast, GF109203X, a selective
      inhibitor of classical PKC and PKCepsilon, did not affect the phosphorylation or
      translocation of p47phox, suggesting that PKCdelta, -theta;, or -eta is required.
      Furthermore, rottlerin (at doses that inhibit PKCdelta activity) inhibited the
      phosphorylation and translocation of p47phox. Rottlerin also inhibited O2
      production at similar doses. In addition to pharmacological inhibitors, PKCdelta
      specific antisense oligodeoxyribonucleotides were used. PKCdelta antisense
      oligodeoxyribonucleotides inhibited the phosphorylation and translocation of
      p47phox in activated human monocytes. We also show, using the recombinant p47phox
      GST fusion protein, that p47phox can serve as a substrate for PKCdelta in vitro.
      Furthermore, lysate-derived PKCdelta from activated monocytes phosphorylated
      p47phox in a rottlerin-sensitive manner. Together, these data suggest that
      PKCdelta plays a pivotal role in stimulating monocyte NADPH oxidase activity
      through its regulation of the phosphorylation and translocation of p47phox.

PMID- 15494526
TI  - Urokinase induces basophil chemotaxis through a urokinase receptor epitope that
      is an endogenous ligand for formyl peptide receptor-like 1 and -like 2.
AB  - Basophils circulate in the blood and are able to migrate into tissues at sites of
      inflammation. Urokinase plasminogen activator (uPA) binds a specific high
      affinity surface receptor (uPAR). The uPA-uPAR system is crucial for cell
      adhesion and migration, and tissue repair. We have investigated the presence and
      function of the uPA-uPAR system in human basophils. The expression of uPAR was
      found at both mRNA and protein levels. The receptor was expressed on the cell
      surface of basophils, in the intact and cleaved forms. Basophils did not express
      uPA at either the protein or mRNA level. uPA (10(-12)-10(-9) M) and its uPAR
      binding N-terminal fragment (ATF) were potent chemoattractants for basophils, but
      did not induce histamine or cytokine release. Inactivation of uPA enzymatic
      activity by di-isopropyl fluorophosphate did not affect its chemotactic activity.
      A polyclonal Ab against uPAR inhibited uPA-dependent basophil chemotaxis. The
      uPAR-derived peptide 84-95 (uPAR84-95) induced basophil chemotaxis. Basophils
      expressed mRNA for the formyl peptide receptors formyl peptide receptor (FPR),
      FPR-like 1 (FPRL1), and FPRL2. The FPR antagonist cyclosporin H prevented
      chemotaxis induced by FMLP, but not that induced by uPA and uPAR84-95. Incubation
      of basophils with low and high concentrations of FMLP, which desensitize FPR and
      FPRL1, respectively, but not FPRL2, slightly reduced the chemotactic response to
      uPA and uPAR84-95. In contrast, desensitization with WKYMVm, which also binds
      FPRL2, markedly inhibited the response to both molecules. Thus, uPA is a potent
      chemoattractant for basophils that seems to act through exposure of the
      chemotactic uPAR epitope uPAR84-95, which is an endogenous ligand for FPRL2 and
      FPRL1.

PMID- 15494527
TI  - Toll receptor-mediated regulation of NADPH oxidase in human dendritic cells.
AB  - Activation of NADPH oxidase represents an essential mechanism of defense against
      pathogens. Dendritic cells (DC) are phagocytic cells specialized in Ag
      presentation rather than in bacteria killing. Human monocyte-derived DC were
      found to express the NADPH oxidase components and to release superoxide anions in
      response to phorbol esters and phagocytic agonists. The NADPH oxidase components
      p47phox and gp91phox were down-regulated during monocyte differentiation to DC,
      and maturation of DC with pathogen-derived molecules, known to activate TLRs,
      increased p47phox and gp91phox expression and enhanced superoxide anions release.
      Similar results were obtained with plasmacytoid DC following maturation with
      influenza virus. In contrast, activation of DC by immune stimuli (CD40 ligand)
      did not regulate NADPH oxidase components or respiratory burst. NADPH oxidase
      derived oxygen radicals did not play any role in DC differentiation, maturation,
      cytokine production, and induction of T cell proliferation, as based on the
      normal function of DC generated from chronic granulomatous disease patients and
      the use of an oxygen radical scavenger. However, NADPH oxidase activation was
      required for DC killing of intracellular Escherichia coli. It is likely that the
      selective regulation of oxygen radicals production by pathogen-activated DC may
      function to limit pathogen dissemination during DC trafficking to secondary
      lymphoid tissues.

PMID- 15494528
TI  - The inhibitory receptor PIR-B negatively regulates neutrophil and macrophage
      integrin signaling.
AB  - The Ig-like receptor family member, PIR-B, has been shown to play an inhibitory
      role in receptor signaling within B cells, mast cells, and dendritic cells. As it
      has been implicated in integrin-mediated responses, we investigated the effect of
      loss of the PIR-B protein on integrin-mediated signaling in primary murine
      myeloid cells. The pir-b-/- neutrophils displayed enhanced respiratory burst,
      secondary granule release, and a hyperadhesive phenotype when plated on surfaces
      coated with either extracellular matrix proteins or cellular adhesion molecules
      in the presence or absence of the soluble inflammatory agonist TNF-alpha. The pir
      b-/- and wild-type cells responded equivalently when stimulated with TNF-alpha in
      suspension, indicating that the hyperresponsive phenotype of the pir-b-/- cells
      during adhesion was due to enhanced integrin signaling. Both wild-type and pir-b
      /- neutrophils expressed similar levels of integrin subunits. Primary bone marrow
      derived macrophages from pir-b-/- mice were also hyperadhesive and spread more
      rapidly than wild-type cells following plating on surfaces that cross-linked
      cellular beta2 integrins. Biochemical analysis of macrophages from pir-b-/- mice
      revealed enhanced phosphorylation and activation of proteins involved in integrin
      signaling. These observations point to a nonredundant role for PIR-B in the
      regulation of leukocyte integrin signaling.

PMID- 15494529
TI  - Selective blockade of NF-kappa B activity in airway immune cells inhibits the
      effector phase of experimental asthma.
AB  - Knockout mice studies have revealed that NF-kappaB plays a critical role in Th2
      cell differentiation and is therefore required for induction of allergic airway
      inflammation. However, the questions of whether NF-kappaB also plays a role in
      the effector phase of airway allergy and whether inhibiting NF-kappaB could have
      therapeutic value in the treatment of established asthma remain unanswered. To
      address these issues, we have assessed in OVA-sensitized wild-type mice the
      effects of selectively antagonizing NF-kappaB activity in the lungs during OVA
      challenge. Intratracheal administration of NF-kappaB decoy oligodeoxynucleotides
      to OVA-sensitized mice led to efficient nuclear transfection of airway immune
      cells, but not constitutive lung cells and draining lymph node cells, associated
      with abrogation of NF-kappaB activity in the airways upon OVA provocation. NF
      kappaB inhibition was associated with strong attenuation of allergic lung
      inflammation, airway hyperresponsiveness, and local production of mucus, IL-5, IL
      13, and eotaxin. IL-4 and OVA-specific IgE and IgG1 production was not reduced.
      This study demonstrates for the first time that activation of NF-kappaB in local
      immune cells is critically involved in the effector phase of allergic airway
      disease and that specific NF-kappaB inhibition in the lungs has therapeutic
      potential in the control of pulmonary allergy.

PMID- 15494530
TI  - Interference with heparin binding and oligomerization creates a novel anti
      inflammatory strategy targeting the chemokine system.
AB  - A hallmark of autoimmunity and other chronic diseases is the overexpression of
      chemokines resulting in a detrimental local accumulation of proinflammatory
      immune cells. Chemokines play a pivotal role in cellular recruitment through
      interactions with both cell surface receptors and glycosaminoglycans (GAGs). Anti
      inflammatory strategies aimed at neutralizing the chemokine system have to-date
      targeted inhibition of the receptor-ligand interaction with receptor antagonists.
      In this study, we describe a novel strategy to modulate the inflammatory process
      in vivo through mutation of the essential heparin-binding site of a
      proinflammatory chemokine, which abrogates the ability of the protein to form
      higher-order oligomers, but retains receptor activation. Using well-established
      protocols to induce inflammatory cell recruitment into the peritoneal cavity,
      bronchoalveolar air spaces, and CNS in mice, this non-GAG binding variant of
      RANTES/CCL5 designated [44AANA47]-RANTES demonstrated potent inhibitory capacity.
      Through a combination of techniques in vitro and in vivo, [44AANA47]-RANTES
      appears to act as a dominant-negative inhibitor for endogenous RANTES, thereby
      impairing cellular recruitment, not through a mechanism of desensitization.
      [44AANA47]-RANTES is unable to form higher-order oligomers (necessary for the
      biological activity of RANTES in vivo) and importantly forms nonfunctional
      heterodimers with the parent chemokine, RANTES. Therefore, although retaining
      receptor-binding capacity, altering the GAG-associated interactive site of a
      proinflammatory chemokine renders it a dominant-negative inhibitor, suggesting a
      powerful novel approach to generate disease-modifying anti-inflammatory reagents.

PMID- 15494531
TI  - A role for NF-kappa B subunits p50 and p65 in the inhibition of
      lipopolysaccharide-induced shock.
AB  - To evaluate the possibility that NF-kappaB subunits p50 and p65 have a role in
      limiting the systemic inflammatory response induced by endotoxin, we compared the
      susceptibility of wild-type (WT), p65+/-, p50-/-, and p50-/-p65+/- (3X) mice to
      LPS-induced shock. Interestingly, whereas p65+/- mice were no more sensitive than
      WT mice to LPS-induced shock, 3X mice were exquisitely sensitive to the toxic
      effects of LPS. Mice lacking p50 alone displayed an intermediate phenotype.
      Sensitivity to LPS was a property of the innate immune system and was
      characterized by elevated circulating levels of TNF in both p50-/- and 3X mice.
      The ability of LPS to induce shock depended upon TNF, and 3X mice were
      significantly more sensitive to the toxic effects of TNF than were p50-deficient
      mice. The expression of several LPS-inducible proinflammatory genes, including
      IFN-gamma, was significantly higher within the spleens of p50-/- mice than in the
      spleens of WT mice, and interestingly, the expression of IFN-gamma was augmented
      still further within the spleens of 3X mice. These results demonstrate that NF
      kappaB subunits p50 and p65 have critical inhibitory functions during the
      systemic response to LPS and raise the possibility that these functions could be
      essential in preventing mortality associated with systemic inflammatory response
      syndromes.

PMID- 15494532
TI  - Green tea epigallocatechin-3-gallate mediates T cellular NF-kappa B inhibition
      and exerts neuroprotection in autoimmune encephalomyelitis.
AB  - Recent studies in multiple sclerosis and its animal model, experimental
      autoimmune encephalomyelitis (EAE), point to the fact that even in the early
      phase of inflammation, neuronal pathology plays a pivotal role in the sustained
      disability of affected individuals. We show that the major green tea constituent,
      (-)-epigallocatechin-3-gallate (EGCG), dramatically suppresses EAE induced by
      proteolipid protein 139-151. EGCG reduced clinical severity when given at
      initiation or after the onset of EAE by both limiting brain inflammation and
      reducing neuronal damage. In orally treated mice, we found abrogated
      proliferation and TNF-alpha production of encephalitogenic T cells. In human
      myelin-specific CD4+ T cells, cell cycle arrest was induced, down-regulating the
      cyclin-dependent kinase 4. Interference with both T cell growth and effector
      function was mediated by blockade of the catalytic activities of the 20S/26S
      proteasome complex, resulting in intracellular accumulation of IkappaB-alpha and
      subsequent inhibition of NF-kappaB activation. Because its structure implicates
      additional antioxidative properties, EGCG was capable of protecting against
      neuronal injury in living brain tissue induced by N-methyl-D-aspartate or TRAIL
      and of directly blocking the formation of neurotoxic reactive oxygen species in
      neurons. Thus, a natural green tea constituent may open up a new therapeutic
      avenue for young disabled adults with inflammatory brain disease by combining, on
      one hand, anti-inflammatory and, on the other hand, neuroprotective capacities.

PMID- 15494533
TI  - Crucial role of inhibitor of DNA binding/differentiation in the vascular
      endothelial growth factor-induced activation and angiogenic processes of human
      endothelial cells.
AB  - Angiogenesis plays a pivotal role in the aggressive proliferation of synovial
      cells in rheumatoid arthritis. We have previously reported the overexpression of
      inhibitor of DNA binding/differentiation (Id) in the endothelial cells within the
      synovial tissues of rheumatoid arthritis. In this study, we investigated the role
      of Id in inflammation and angiogenesis in an in vitro model using HUVECs.
      Vascular endothelial growth factor (VEGF) and TGFbeta induced the expression of
      Id1 and Id3 in HUVECs. Forced expression of Id induced proliferative activity in
      HUVECs accompanied by down-regulation of p16INK4a. Overexpression of Id enhanced
      expression of ICAM-1 and E-selectin, and induced angiogenic processes such as
      transmigration, matrix metalloproteinase-2 and -9 expression, and tube formation.
      In contrast, knockdown of Id1 and Id3 with RNA interference abolished
      proliferation, activation, and angiogenic processes of HUVECs induced by VEGF.
      These results indicated that Id plays a crucial role in VEGF-induced signals of
      endothelial cells by causing activation and potentiation of angiogenic processes.
      Based on these findings, it was proposed that inhibition of expression and/or
      function of Id1 and Id3 may potentially be of therapeutic value for conditions
      associated with pathological angiogenesis.

PMID- 15494534
TI  - CC chemokine ligand 18, an atopic dermatitis-associated and dendritic cell
      derived chemokine, is regulated by staphylococcal products and allergen exposure.
AB  - Atopic dermatitis is a chronic inflammatory skin disease with a steadily
      increasing prevalence. Exposure to allergens or bacterial superantigens triggers
      T and dendritic cell (DC) recruitment and induces atopic skin inflammation. In
      this study, we report that among all known chemokines CCL18/DC-CK1/PARC
      represents the most highly expressed ligand in atopic dermatitis. Moreover, CCL18
      expression is associated with an atopic dermatitis phenotype when compared with
      other chronic inflammatory skin diseases. DCs either dispersed within the dermis
      or clustering at sites showing perivascular infiltrates are abundant sources of
      CCL18. In vitro, microbial products including LPS, peptidoglycan, and mannan, as
      well as the T cell-derived activation signal CD40L, induced CCL18 in monocytes.
      In contrast to monocytes, monocyte-derived, interstitial-type, and Langerhans
      type DCs showed a constitutive and abundant expression of CCL18. In comparison to
      Langerhans cells, interstitial-type DCs produced higher constitutive levels of
      CCL18. In vivo, topical exposure to the relevant allergen or the superantigen
      staphylococcal enterotoxin B, resulted in a significant induction of CCL18 in
      atopic dermatitis patients. Furthermore, in nonatopic NiSO4-sensitized
      individuals, only relevant allergen but not irritant exposure resulted in the
      induction of CCL18. Taken together, findings of the present study demonstrate
      that CCL18 is associated with an atopy/allergy skin phenotype, and is expressed
      at the interface between the environment and the host by cells constantly
      screening foreign Ags. Its regulation by allergen exposure and microbial products
      suggests an important role for CCL18 in the initiation and amplification of
      atopic skin inflammation.

PMID- 15494535
TI  - Targeting IL-15 receptor-bearing cells with an antagonist mutant IL-15/Fc protein
      prevents disease development and progression in murine collagen-induced
      arthritis.
AB  - It has been suggested that the inflammatory cytokine IL-15 plays an important
      role in the development of several autoimmune diseases, including rheumatoid
      arthritis. We have generated a unique lytic and antagonistic IL-15
      mutant/Fcgamma2a fusion protein (CRB-15) that targets the IL-15R. In the present
      study we examined the effects of targeting the IL-15R on the prevention and
      treatment of collagen-induced arthritis (CIA) in mice and probed the possible
      mechanisms of action of this IL-15 mutant/Fcgamma2a protein. Upon immunization
      with type II collagen, DBA/1 mice develop severe articular inflammation and
      destruction. Treatment of DBA/1 mice with a brief course of CRB-15 at the time of
      type II collagen challenge markedly inhibited the incidence and severity of
      arthritis. Moreover, in animals with ongoing established arthritis, treatment
      with CRB-15 effectively blocked disease progression compared with that in control
      treated animals. The therapeutic effect of CRB-15 on either disease development
      or disease progression is remarkably stable, because withdrawal of treatment did
      not lead to disease relapse. A detailed analysis revealed that treatment with CRB
      15 decreased synovitis in the joints; reduced bone erosion and cartilage
      destruction; reduced in situ production of the proinflammatory cytokines TNF
      alpha, IL-1beta, IL-6, and IL-17; and decreased the responder frequency of
      autoreactive T cells. Our study suggests that the effective targeting of IL-15R
      triggered events with CRB-15 can be of therapeutic importance in the treatment of
      rheumatoid arthritis.

PMID- 15494536
TI  - Mixed xenogeneic chimerism induces donor-specific humoral and cellular immune
      tolerance for cardiac xenografts.
AB  - Xenotransplantation has been suggested as a potential solution to the critical
      shortage of donor organs. However, success has been limited by the vigorous
      rejection response elicited against solid organs transplanted across species
      barriers. Mixed xenogeneic bone marrow chimeras resulting from the
      transplantation of a mixture of host and donor marrow (B10 mouse + F344 rat -->
      B10 mouse) results in donor-specific cross-species transplantation tolerance for
      subsequent nonvascularized skin and islet grafts. Furthermore, compared with
      fully xenogeneic chimeras (rat --> mouse), mixed xenogeneic chimeras exhibit
      superior immunocompetence for infectious agents in vivo and in vitro, suggesting
      that the immune system is intact. The ability to establish long-term humoral and
      cellular tolerance for primarily vascularized xenografts in vivo, in the setting
      of both recipient and donor Ig and effector cell production, has not previously
      been characterized. Mixed xenogeneic chimeras exhibit donor-specific humoral
      tolerance as evident by the absence of anti-donor Ab and Ab-dependent donor
      specific cytotoxicity in vitro and intravascular IgM deposition within donor
      strain (F344) cardiac xenografts in vivo. F344 cardiac xenografts are accepted
      (median > or =180 days) without clinical or histologic evidence of rejection,
      suggesting cellular tolerance. In contrast, MHC-disparate third-party mouse
      (B10.BR) and rat (ACI or WF) grafts are rejected (median of 23 and 41 days,
      respectively) in association with extensive mononuclear cell infiltration and
      vascular deposits of mouse IgM. These results demonstrate that mixed xenogeneic
      chimerism establishes donor-specific humoral and cellular tolerance and permits
      the successful transplantation of even primarily vascularized xenografts in the
      setting of intact Ab production.

PMID- 15494537
TI  - Intravenous injection of a D1 protein of the Smith proteins postpones murine
      lupus and induces type 1 regulatory T cells.
AB  - T cells that recognize nucleoproteins are required for the production of anti
      dsDNA Abs involved in lupus development. SmD1 83-119 (a D1 protein of the Smith
      (Sm) proteins, part of small nuclear ribonucleoprotein) was recently shown to
      provide T cell help to anti-dsDNA Abs in the NZB/NZW model of lupus. Using this
      model in the present study, we showed that high dose tolerance to SmD1 (600-1000
      microg i.v. of SmD1(83-119) peptide/mo) delays the production of autoantibodies,
      postpones the onset of lupus nephritis as confirmed by histology, and prolongs
      survival. Tolerance to SmD1 83-119 was adoptively transferred by CD90+ T cells,
      which also reduce T cell help for autoreactive B cells in vitro. One week after
      SmD1 83-119 tolerance induction in prenephritic mice, we detected cytokine
      changes in cultures of CD90+ T and B220+ B cells with decreased IFN-gamma and IL
      4 expression and an increase in TGFbeta. Increased frequencies of regulatory IFN
      gamma+ and IL10+ CD4+ T cells were later detected. Such regulatory IL-10+/IFN
      gamma+ type 1 regulatory T cells prevented autoantibody generation and anti-CD3
      induced proliferation of naive T cells. In conclusion, these results indicate
      that SmD1 83-119 peptide may play a dominant role in the activation of helper and
      regulatory T cells that influence autoantibody generation and murine lupus.

PMID- 15494538
TI  - Long-term stable expanded human CD4+ T cell clones specific for human
      cytomegalovirus are distributed in both CD45RAhigh and CD45ROhigh populations.
AB  - T cells play an important role in the control of human CMV (HCMV) infection.
      Peripheral blood CD4+ T cell proliferative responses to the HCMV lower tegument
      protein pp65 have been detected in most healthy HCMV carriers. To analyze the
      clonal composition of the CD4+ T cell response against HCMV pp65, we
      characterized three MHC class II-restricted peptide epitopes within pp65 in virus
      carriers. In limiting dilution analysis, we observed high frequencies of pp65
      peptide-specific CD4+ T cells, many of which expressed peptide-specific
      cytotoxicity in addition to IFN-gamma secretion. We analyzed the clonal
      composition of CD4+ T cells specific for defined HCMV peptides by generating
      multiple independent peptide-specific CD4+ clones and sequencing the TCR beta
      chain. In a given carrier, most of the CD4+ clones specific for a defined pp65
      peptide had identical TCR nucleotide sequences. We used clonotype oligonucleotide
      probing to quantify the size of individual peptide-specific CD4+ clones in whole
      PBMC and in purified subpopulations of CD45RAhighCD45ROlow and
      CD45RAlowCD45ROhigh cells. Individual CD4+ T cell clones could be large (0.3-1.5%
      of all CD4+ T cells in PBMC) and were stable over time. Cells of a single clone
      were distributed in both the CD45RAhigh and CD45ROhigh subpopulations. In one
      carrier, the virus-specific clone was especially abundant in the small CD28
      CD45RAhigh CD4+ T cell subpopulation. Our study demonstrates marked clonal
      expansion and phenotypic heterogeneity within daughter cells of a single virus
      specific CD4+ T cell clone, which resembles that seen in the CD8+ T cell response
      against HCMV pp65.

PMID- 15494539
TI  - Identification of a human HLA-E-restricted CD8+ T cell subset in volunteers
      immunized with Salmonella enterica serovar Typhi strain Ty21a typhoid vaccine.
AB  - Our previous studies in volunteers immunized with Salmonella enterica serovar
      Typhi (S. Typhi) have suggested an important role for CD8+ T cells in host
      defense. In this study we describe a novel subset of nonclassical human HLA-E
      restricted S. Typhi-specific CD8+ T cells derived from PBMC of Ty21a typhoid
      vaccinees. CD3+CD8+CD4-CD56- T cells effectively killed S. Typhi-infected targets
      regardless of whether they share classical HLA class I molecules with them, by a
      FAS-independent, granule-dependent mechanism, as evidenced by induction of
      granzyme B release and the blocking effects of concanamycin and strontium ions.
      The expression of HLA-E Ags, but not CD1-a, -b, or -c, on the membrane of S.
      Typhi-infected targets rendered them susceptible to lysis. Moreover, anti-HLA-E
      Abs partially blocked these responses. We also demonstrated that presentation of
      S. Typhi Ags via HLA-E could stimulate IFN-gamma production. Increases in the net
      frequency of IFN-gamma spot-forming cells were observed in the presence of
      targets coated with peptides that contain S. Typhi GroEL HLA-E binding motifs.
      These results demonstrate that HLA-E binds nonamer peptides derived from
      bacterial proteins and trigger CD8+-mediated lysis and IFN-gamma production when
      exposed to infected targets, raising the possibility that this novel effector
      mechanism might contribute to host defense against intracellular bacterial
      infections.

PMID- 15494540
TI  - Cellular immune responses to the hepatitis B virus polymerase.
AB  - CD4 T cells play an important role in hepatitis B virus (HBV) infection by
      secretion of Th1 cytokines that down-regulate HBV replication, and by promoting
      CD8 T cell and B cell responses. We have identified and characterized 10 CD4 T
      cell epitopes within polymerase and used them to analyze the immunological
      effects of long-term antiviral therapy as compared with spontaneous recovery from
      HBV infection. Candidate epitopes were tested for binding to 14 HLA-DR molecules
      and in IFN-gamma ELISPOT and cytotoxicity assays using peripheral blood
      lymphocytes from 66 HBV-infected patients and 16 uninfected controls. All 10
      epitopes bound with high affinity to the most prevalent HLA-DR Ags, were
      conserved among HBV genomes, and induced IFN-gamma responses from HBV-specific
      CD4+ T cells. Several epitopes contained nested MHC class I motifs and stimulated
      HBV-specific IFN-gamma production and cytotoxicity of CD8+ T cells. HBV
      polymerase-specific responses were more frequent during acute, self-limited
      hepatitis and after recovery (12 of 18; 67%) than during chronic hepatitis (16 of
      48 (33%); p=0.02). Antiviral therapy of chronic patients restored HBV polymerase
      and core-specific T cell responses during the first year of treatment, but
      thereafter, responses decreased and, after 3 years, were no more frequent than in
      untreated patients. Decreased T cell responsiveness during prolonged therapy was
      associated with increased prevalence of lamivudine-resistant HBV mutants and
      increased HBV titers. The data provide a rationale for the combination of
      antiviral and immunostimulatory therapy. These newly described HBV polymerase
      epitopes could be a valuable component of a therapeutic vaccine for a large and
      ethnically diverse patient population.

PMID- 15494541
TI  - Hypoallergenic variants of the major latex allergen Hev b 6.01 retaining human T
      lymphocyte reactivity.
AB  - Hev b 6.01 is a major allergen of natural rubber latex with sensitization of 70
      86% of latex glove-allergic subjects. Recently, we mapped the immunodominant T
      cell sites of Hev b 6.01 to the highly IgE-reactive hevein (Hev b 6.02) domain.
      Hev b 6.01 contains 14 cysteine residues with multiple disulphide bridges
      stabilizing tertiary conformation. With the goal of a standardized specific
      immunotherapy we developed hypoallergenic Hev b 6.01 mutants by site-directed
      mutagenesis of selected cysteine residues (3, 12, 17, and 41) within the Hev b
      6.02 domain. Peptides corresponding to the Hev b 6.02 domain of two of the
      mutants were also synthesized. These mutants and peptide variants showed markedly
      decreased or ablated latex-allergic patient serum IgE binding by immunoblotting
      and ELISA. Basophil activation testing confirmed markedly decreased activation
      with successive cysteine substitutions of the mutants and complete abrogation
      with the Hev b 6.02 (Cys 3, 12, 17, 41 Ala) peptide. Retention of T cell
      reactivity is crucial for effective specific immunotherapy and all mutants and
      peptide variants maintained their latex-specific T cell reactivity. The ablated
      allergenicity but retained T cell reactivity of the Hev b 6.02 (Cys 3, 12, 17, 41
      Ala) peptide suggests this peptide is a suitable candidate for inclusion in a
      latex immunotherapy preparation.

PMID- 15494542
TI  - Costimulation requirements of induced murine systemic autoimmune disease.
AB  - Costimulation between T cells and APC is required for productive immune
      responses. A number of receptor/ligand pairs have been shown to mediate
      costimulation, including CD28/B7 molecules (CD80 and CD86), CD40/CD40 ligand
      (CD40L, CD154), and LFA-1 (CD18)/ICAM-1 (CD54). T-B cell costimulation also plays
      a significant role in autoimmune diseases such as systemic lupus erythematosus.
      Murine HgCl2-induced autoimmunity (mHgIA) is a T cell-dependent systemic
      autoimmune disease that shares a number of common pathogenic mechanisms with
      idiopathic lupus. In this report, the significance of costimulation in mHgIA is
      examined by attempting to induce disease in mice deficient in either CD40L, CD28,
      or ICAM-1. Unlike absence of ICAM-1, homozygous deficiencies in either CD40L or
      CD28 significantly reduced the development of mHgIA. CD40L displayed a gene
      dosage effect as heterozygous mice also showed reduction of autoantibody
      responses and immunopathology. Markers of T cell activation such as CD44 and CTLA
      4 were associated with disease expression in wild-type and ICAM-1-deficient mice
      but not in CD40L- or CD28-deficient mice. Absence of CTLA-4 expression in CD40L-/
      mice suggests that signaling via both CD28 and CD40L is important for T cell
      activation and subsequent autoimmunity in mHgIA. Attempts to circumvent the
      absence of CD40L by increasing CD28 signaling via agonistic Ab failed to elicit
      CTLA-4 expression. These findings indicate that breaking of self-tolerance in
      mHgIA requires signaling via both the CD28/B7 and CD40/CD40L pathways.

PMID- 15494543
TI  - Poly(ADP-ribose) polymerase-1 gene ablation protects mice from ischemic renal
      injury.
AB  - Increased generation of reactive oxygen species (ROS) and the subsequent DNA
      damage and excessive activation of poly(ADP-ribose) polymerase-1 (PARP-1) have
      been implicated in the pathogenesis of ischemic injury. We previously
      demonstrated that pharmacological inhibition of PARP protects against ischemic
      renal injury (IRI) in rats (Martin DR, Lewington AJ, Hammerman MR, and Padanilam
      BJ. Am J Physiol Regul Integr Comp Physiol 279: R1834-R1840, 2000). To further
      define the role of PARP-1 in IRI, we tested whether genetic ablation of PARP-1
      attenuates tissue injury after renal ischemia. Twenty-four hours after
      reperfusion following 37 min of bilateral renal pedicle occlusion, the effects of
      the injury on renal functions in PARP-/- and PARP+/+ mice were assessed by
      determining glomerular filtration rate (GFR) and the plasma levels of creatinine.
      The levels of plasma creatinine were decreased and GFR was augmented in PARP-/-
      mice. Morphological evaluation of the kidney tissues showed that the extent of
      damage due to the injury in PARP-/- mice was less compared with their wild-type
      counterparts. The levels of ROS and DNA damage were comparable in the injured
      kidneys of PARP+/+ and PARP-/- mice. PARP activity was induced in ischemic
      kidneys of PARP+/+ mice at 6-24 h postinjury. At 6, 12, and 24 h after injury,
      ATP levels in the PARP+/+ mice kidney declined to 28, 26, and 43%, respectively,
      whereas it was preserved close to normal levels in PARP-/- mice. The inflammatory
      cascade was attenuated in PARP-/- mice as evidenced by decreased neutrophil
      infiltration and attenuated expression of inflammatory molecules such as TNF
      alpha, IL-1beta, and intercellular adhesion molecule-1. At 12 h postinjury, no
      apoptotic cell death was observed in PARP-/- mice kidneys. However, by 24 h
      postinjury, a comparable number of cells underwent apoptosis in both PARP-/- and
      PARP+/+ mice kidneys. Thus activation of PARP post-IRI contributes to cell death
      most likely by ATP depletion and augmentation of the inflammatory cascade in the
      mouse model. PARP ablation preserved ATP levels, renal functions, and attenuated
      inflammatory response in the setting of IRI in the mouse model. PARP inhibition
      may have clinical efficacy in preventing the progression of acute renal failure
      complications.

PMID- 15494544
TI  - Parenteral iron compounds sensitize mice to injury-initiated TNF-alpha mRNA
      production and TNF-alpha release.
AB  - Intravenous Fe is widely used to treat anemia in renal disease patients. However,
      concerns of potential Fe toxicity exist. To more fully define its spectrum, this
      study tested Fe's impact on systemic inflammation following either endotoxemia or
      the induction of direct tissue damage (glycerol-mediated rhabdomyolysis). The
      inflammatory response was gauged by tissue TNF-alpha message expression and
      plasma TNF-alpha levels. CD-1 mice received either intravenous Fe sucrose, 
      gluconate, or -dextran (FeS, FeG, or FeD, respectively; 2 mg), followed by either
      endotoxin (LPS) or glycerol injection 0-48 h later. Plasma TNF-alpha was assessed
      by ELISA 2-3 h after the LPS or glycerol challenge. TNF-alpha mRNA expression (RT
      PCR) was measured in the kidney, heart, liver, lung, and spleen with Fe +/- LPS
      treatment. Finally, the relative impacts of intramuscular vs. intravenous Fe and
      of glutathione (GSH) on Fe/LPS- induced TNF-alpha generation were assessed. Each
      Fe preparation significantly enhanced LPS- or muscle injury-mediated TNF-alpha
      generation. This effect was observed for at least 48 h post-Fe injection, a time
      at which plasma iron levels were increased by levels insufficient to fully
      saturate transferrin. Fe did not independently increase plasma TNF-alpha or
      tissue mRNA. However, it potentiated postinjury-induced TNF-alpha mRNA increments
      and did so in an organ-specific fashion (kidney, heart, and lung; but not in
      liver or spleen). Intramuscular administration, but not GSH treatment, negated
      Fe's ability to synergize LPS-mediated TNF-alpha release. We conclude 1)
      intravenous Fe can enhance TNF-alpha generation during LPS- or glycerol-induced
      tissue damage; 2) increased TNF-alpha gene transcription in the kidney, heart,
      and lung may contribute to this result; and 3) intramuscular administration, but
      not GSH, might potentially mitigate some of Fe's systemic toxic effects.

PMID- 15494545
TI  - Micropuncture determination of nephron function in mice without tissue
      angiotensin-converting enzyme.
AB  - To determine the role of the local renin-angiotensin system in renal function,
      micropuncture was performed on two lines of mice in which genetic changes to the
      angiotensin-converting enzyme (ACE) gene markedly reduced or eliminated the
      expression of renal tissue ACE. Whereas blood pressure is low in one line (ACE
      2/2), it is normal in the other (ACE 1/3) due to ectopic hepatic ACE expression.
      When normalized for renal size, levels of glomerular filtration rate [GFR; microl
      x min(-1) x g kidney wt(-1) (KW)] and single-nephron GFR (SNGFR; nl x min(-1) x g
      KW(-1)) were similar between wild-type (WT) and ACE 1/3 mice, while both measures
      were significantly reduced in ACE 2/2 mice (WT: 500 +/- 63 and 41.7 +/- 3.5; ACE
      1/3: 515.8 +/- 71 and 44.3 +/- 3.3; ACE 2/2: 131.4 +/- 23 and 30.3 +/- 3.5).
      Proximal fractional reabsorption was not significantly different between WT and
      ACE 1/3 mice (51 +/- 3.5 and 49 +/- 2.3%), and it was increased significantly in
      ACE 2/2 mice (74 +/- 3.5%). Infusion of ANG II (50 ng x kg(-1) x min(-1))
      increased mean arterial pressure by approximately 7 mmHg in all groups of mice
      and reduced SNGFR in WT and ACE 1/3 mice (to 30.9 +/- 2.8 and 31.9 +/- 2.5 nl x
      min(-1) x g KW(-1)) while increasing it in ACE 2/2 mice (to 55.3 +/- 5.3 nl x
      min(-1) x g KW(-1)) despite an increase in total renal vascular resistance. The
      tubuloglomerular feedback (TGF) response was markedly reduced in ACE 1/3 mice
      (stop-flow pressure change -2.5 +/- 0.9 mmHg) compared with WT despite similar
      blood pressures (-8.3 +/- 0.6 mmHg). In ACE 2/2 mice, TGF was absent (-0.7 +/-
      0.2 mmHg). We conclude that the chronic lack of ACE, and presumably ANG II
      generation, in the proximal tubule was not associated with sustained proximal
      fluid transport defects. However, renal tissue ACE is an important contributor to
      TGF.

PMID- 15494546
TI  - Differential localization of mammalian Lin-7 (MALS/Veli) PDZ proteins in the
      kidney.
AB  - Lin-7 PDZ proteins, also called MALS or Velis, have been shown to coordinate
      basolateral membrane expression of various target proteins in renal epithelial
      cell models. Three different Lin-7/MALS/Veli isoforms, encoded by separate genes,
      have been identified. Here, we show that each Lin-7/MALS/Veli isoform is
      expressed in the kidney. Using MALS isoform-specific antibodies in combination
      with cell-specific marker antibodies, we found the products of the three
      mammalian Lin-7/MALS/Veli genes are differentially expressed along the length of
      the nephron. MALS/Veli 1 is predominately expressed in the glomerulus, thick
      ascending limb of Henle's loop (TAL), and the distal convoluted tubule (DCT).
      MALS/Veli 2 is exclusively expressed in the vasa recta. MALS/Veli 3 is largely
      located in the DCT and collecting duct. The subcellular localization of MALS/Veli
      proteins can vary, depending on the isoform and the cell type. In contrast to the
      predominate basolateral location of MALS/Veli 1 in the TAL and DCT and MALS/Veli
      3 in the DCT, MALS/Veli 1 is found diffusely throughout the cytosol of
      intercalated cells. In the collecting duct, MALS/Veli 3 is chiefly located on the
      basal membrane. Collectively, these results suggest that different MALS/Veli
      isoforms may carry out cell type-specific functions. The TAL and distal segments
      appear to have the most significant capacity for a basolateral membrane-targeting
      mechanism involving different MALS/Veli isoforms.

PMID- 15494547
TI  - Insulin potentiates AVP-induced AQP2 expression in cultured renal collecting duct
      principal cells.
AB  - In the renal collecting duct (CD), water reabsorption depends on the presence of
      aquaporin-2 (AQP2) in the apical membrane of principal cells. AQP2 expression and
      subcellular repartition are under the control of AVP. Some pieces of experimental
      evidence indicate that additional hormonal factors, including insulin, may also
      control AQP2 expression and thereby CD water permeability. We have previously
      shown that AVP induces endogenous AQP2 expression in cultured mouse mpkCCD(cl4)
      CD principal cells (23). In the present study, we investigated the effect of
      insulin on AQP2 expression in mpkCCD(cl4) cells. Addition of insulin to the basal
      medium of cells grown on filters slightly increased AQP2 mRNA and protein
      expression, whereas insulin potentiated the effect of AVP. The potentiation of
      AVP-induced AQP2 expression by insulin was abolished by actinomycin D, a
      transcriptional inhibitor. Analysis of AQP2 protein expression under conditions
      of AVP washout and/or in the presence of chloroquine, a lysosomal degradation
      inhibitor, revealed that insulin did not significantly alter AQP2 protein
      degradation. Inhibition of ERK, p38 kinase, and phosphatidylinositol 3'-kinase
      (PI 3-kinase) activities prevented the insulin-induced stimulation of AQP2
      expression, whereas inhibition of PKC has no effect. Taken together, our results
      indicate that insulin increased AQP2 protein expression mostly through increased
      AQP2 mRNA levels in cultured mpkCCD(cl4) cells. This effect most likely relies on
      increased AQP2 gene transcription in response to MAPK and PI 3-kinase activation.

PMID- 15494548
TI  - Valdecoxib: assessment of cyclooxygenase-2 potency and selectivity.
AB  - The discovery of a second isoform of cyclooxygenase (COX) led to the search for
      compounds that could selectively inhibit COX-2 in humans while sparing
      prostaglandin formation from COX-1. Celecoxib and rofecoxib were among the
      molecules developed from these efforts. We report here the pharmacological
      properties of a third selective COX-2 inhibitor, valdecoxib, which is the most
      potent and in vitro selective of the marketed COX-2 inhibitors that we have
      studied. Recombinant human COX-1 and COX-2 were used to screen for new highly
      potent and in vitro selective COX-2 inhibitors and compare kinetic mechanisms of
      binding and enzyme inhibition with other COX inhibitors. Valdecoxib potently
      inhibits recombinant COX-2, with an IC(50) of 0.005 microM; this compares with IC
      values of 0.05 microM for celecoxib, 0.5 microM for rofecoxib, and 5 microM for
      etoricoxib. Unique binding interactions of valdecoxib with COX-2 translate into a
      fast rate of inactivation of COX-2 (110,000 M/s compared with 7000 M/s for
      rofecoxib and 80 M/s for etoricoxib). The overall saturation binding affinity for
      COX-2 of valdecoxib is 2.6 nM (compared with 1.6 nM for celecoxib, 51 nM for
      rofecoxib, and 260 nM for etoricoxib), with a slow off-rate (t(1/2) approximately
      98 min). Valdecoxib inhibits COX-1 in a competitive fashion only at very high
      concentrations (IC(50) = 150 microM). Collectively, these data provide a
      mechanistic basis for the potency and in vitro selectivity of valdecoxib for COX
      2. Valdecoxib showed similar activity in the human whole-blood COX assay (COX-2
      IC(50) = 0.24 microM; COX-1 IC(50) = 21.9 microM). We also determined whether
      this in vitro potency and selectivity translated to significant potency in vivo.
      In rats, valdecoxib demonstrated marked potency in acute and chronic models of
      inflammation (air pouch ED(50) = 0.06 mg/kg; paw edema ED(50) = 5.9 mg/kg;
      adjuvant arthritis ED(50) = 0.03 mg/kg). In these same animals, COX-1 was spared
      at doses greater than 200 mg/kg. These data provide a basis for the observed
      potent anti-inflammatory activity of valdecoxib in humans.

PMID- 15494549
TI  - Protein kinase C signaling as a survival pathway against CYP2E1-derived oxidative
      stress and toxicity in HepG2 cells.
AB  - Hepatic induction of CYP2E1 is a major pathway involved in oxidative stress and
      damage caused by chronic ethanol consumption; CYP2E1 also promotes the activation
      of a variety of hepatotoxins to reactive intermediates. Phorbol esters activate
      protein kinase C (PKC), thereby blocking cell differentiation and promoting tumor
      growth. In this study, we examined the possible role of PKC signaling as a
      survival pathway against CYP2E1-mediated toxicity using transfected HepG2
      hepatoma cells stably overexpressing CYP2E1 (E47 cells). Cells were exposed to
      arachidonic acid (AA) plus Fe, which has been previously reported to cause a
      synergistic toxicity in E47 cells by a mechanism dependent on CYP2E1 activity and
      involving oxidative stress and lipid peroxidation. Phorbol ester 12-O
      tetradecanoylphorbol 13-acetate (TPA), but not the inactive analog 4-alpha-TPA,
      prevented lipid peroxidation, glutathione depletion, and loss of viability
      produced by AA + Fe in E47 cells. TPA also protected against the toxicity caused
      by AA alone, or by iron alone, in the E47 cells. TPA did not lower but instead
      induced catalytically active CYP2E1 in these cells. The protective effect of TPA
      on CYP2E1-dependent AA + Fe toxicity seemed to involve a PKC-related survival
      mechanism, since PKC inhibitors such as Ro 31-8425 (bisindolylmaleimide X
      hydrochloride) or staurosporine abolished that protection, and activation of PKC
      by TPA was an early event that occurs prior to the developing toxicity. In
      conclusion, PKC activation by TPA prevents CYP2E1-derived acute oxidative stress
      and toxicity in HepG2 cells, and this appears to involve maintenance of the
      intracellular redox homeostasis via PKC signal transduction.

PMID- 15494550
TI  - Efficacy of duloxetine, a potent and balanced serotonergic and noradrenergic
      reuptake inhibitor, in inflammatory and acute pain models in rodents.
AB  - Duloxetine, a selective but balanced serotonergic and noradrenergic reuptake
      inhibitor, was evaluated in the acute nociceptive pain models of tail flick and
      hot plate in mice and in the persistent and/or inflammatory pain models of acetic
      acid-induced writhing in mice, carrageenan-induced thermal hyperalgesia and
      mechanical allodynia in rats, and capsaicin-induced mechanical allodynia in rats.
      In acute pain models, duloxetine had no significant effect on response latency in
      the mouse tail-flick test but produced modest increases in response latencies in
      the mouse hot plate test. Morphine produced dose-related analgesic effects in
      both the mouse tail-flick and hot plate tests. In models of inflammatory and/or
      persistent pain, duloxetine, morphine, and ibuprofen produced dose-related
      decreases in acetic acid-induced writhing in mice. Duloxetine, ibuprofen, and
      gabapentin also produced dose-dependent reversals of both thermal hyperalgesia
      and mechanical allodynia produced by carrageenan in rats. In addition, both
      duloxetine and morphine produced a significant reduction of capsaicin-induced
      mechanical allodynia in rats. Duloxetine and gabapentin were without substantial
      effect on the Rotorod test in mice, whereas morphine and ibuprofen produced a
      significant impairment. Our data indicate that duloxetine may be efficacious in
      the treatment of persistent and/or inflammatory pain states at doses that have
      modest or no effect on acute nociception or motor performance.

PMID- 15494551
TI  - Dopamine D1 and D2 agonist effects on prepulse inhibition and locomotion:
      comparison of Sprague-Dawley rats to Swiss-Webster, 129X1/SvJ, C57BL/6J, and
      DBA/2J mice.
AB  - D2 receptors have been studied in relation to therapeutic uses of dopaminergic
      drugs, and psychomotor stimulant effects [as manifested by decreased prepulse
      inhibition (PPI) of startle and increased locomotor activity] are hallmark
      behavioral effects of D2 agonists in rats. Genetic studies with mutant mice might
      be useful in this line of investigation; however, recent studies suggest that
      mice differ from rats with respect to D2 agonist effects. Accordingly, we studied
      a wide range of doses of the D2-like agonist quinelorane (0.0032-5.6 mg/kg) and
      the D1-like agonist R-6-Br-APB [R(+)-6-bromo-7,8-dihydroxy-3-allyl-1-phenyl
      2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide] (0.032-5.6 mg/kg) in outbred
      Sprague-Dawley rats, outbred Swiss-Webster mice, and inbred 129X1/SvJ, C57BL/6J,
      and DBA/2J mice. Whereas the D2 agonist dose-dependently decreased PPI and
      increased locomotion in rats, neither of these effects was observed in outbred or
      inbred mice. In contrast, the D1 agonist reduced PPI and increased locomotion in
      Sprague-Dawley rats and in Swiss-Webster, 129X1/SvJ, and C57BL/6J mice. Neither
      agonist decreased PPI in DBA/2J mice, although PPI was increased in this strain
      by a D2 antagonist. Pretreatment with either the D2 antagonist eticlopride (1
      mg/kg) or the D1 antagonist SCH39166 [(-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro
      2-hydroxy-N-methyl-5H-benzo[d]naptho-(2,1-b)azepine] (1 mg/kg) prevented the PPI
      disruptive effects of quinelorane in rats and R-6-Br-APB in mice, suggesting
      receptor interactions in both species. In summary, psychomotor stimulant effects
      of a D2 agonist that were robustly observed in outbred rats were absent in
      several outbred and inbred strains of mice. These results may have implications
      for the study of mutant mice to investigate genes involved in psychomotor
      function in humans.

PMID- 15494552
TI  - Selective reversal of hyperglycemia-evoked gastric myoelectric dysrhythmias by
      nitrergic stimulation in healthy humans.
AB  - Acute hyperglycemia disrupts gastric myoelectric rhythm in healthy humans.
      Defective nitrergic function is a factor in animal models of diabetic
      gastropathy. We tested participation of nitrergic pathways in hyperglycemia
      evoked myoelectric dysrhythmias and compared their role in preventing dysrhythmic
      actions of experimental motion sickness. Twelve healthy volunteers underwent
      electrogastrography (EGG) with and without intravenous 20% dextrose to produce
      plasma glucoses of 250 mg/dl. EGG continued for 2 h after oral nitroglycerin (9
      mg) or the cyclic GMP-specific phosphodiesterase inhibitor sildenafil (100 mg).
      In separate studies, 12 volunteers underwent circular vection (60 degrees /s)
      without and 90 min after nitroglycerin (9 mg) or sildenafil (100 mg) with
      concurrent EGG. Hyperglycemia decreased recording time in normal rhythm,
      increased tachygastria more than 3-fold, and decreased power of the dominant
      frequency (P < 0.05). Nitroglycerin and sildenafil reversed effects of
      hyperglycemia, improving normal rhythm, decreasing tachygastria (both P < 0.05),
      and blunting power decreases. Neither agent affected EGG rhythm during
      euglycemia. Vection decreased time in normal rhythm and increased tachygastria (P
      < 0.05). However, nitroglycerin and sildenafil did not reverse dysrhythmic
      effects of vection (P = N.S.). In conclusion, administration of a nitric oxide
      (NO) donor or an inhibitor of cyclic GMP-selective phosphodiesterase reverses the
      dysrhythmic effects of hyperglycemia on gastric myoelectric activity in healthy
      humans. These agents have no effect on dysrhythmias during motion sickness. These
      findings are consistent with selective impairment of nitrergic function in this
      model of diabetic gastropathy and suggest that NO donors and other agents that
      increase NO activity may be useful for treating diabetic dysrhythmias.

PMID- 15494553
TI  - Plant proteins that interact with VirB2, the Agrobacterium tumefaciens pilin
      protein, mediate plant transformation.
AB  - Agrobacterium tumefaciens uses a type IV secretion system (T4SS) to transfer T
      DNA and virulence proteins to plants. The T4SS is composed of two major
      structural components: the T-pilus and a membrane-associated complex that is
      responsible for translocating substrates across both bacterial membranes. VirB2
      protein is the major component of the T-pilus. We used the C-terminal-processed
      portion of VirB2 protein as a bait to screen an Arabidopsis thaliana cDNA library
      for proteins that interact with VirB2 in yeast. We identified three related plant
      proteins, VirB2-interacting protein (BTI) 1 (BTI1), BTI2, and BTI3 with unknown
      functions, and a membrane-associated GTPase, AtRAB8. The three BTI proteins also
      interacted with VirB2 in vitro. Preincubation of Agrobacterium with GST-BTI1
      protein decreased the transformation efficiency of Arabidopsis suspension cells
      by Agrobacterium. Transgenic BTI and AtRAB8 antisense and RNA interference
      Arabidopsis plants are less susceptible to transformation by Agrobacterium than
      are wild-type plants. The level of BTI1 protein is transiently increased
      immediately after Agrobacterium infection. In addition, overexpression of BTI1
      protein in transgenic Arabidopsis results in plants that are hypersusceptible to
      Agrobacterium-mediated transformation. Confocal microscopic data indicate that
      GFP-BTI proteins preferentially localize to the periphery of root cells in
      transgenic Arabidopsis plants, suggesting that BTI proteins may contact the
      Agrobacterium T-pilus. We propose that the three BTI proteins and AtRAB8 are
      involved in the initial interaction of Agrobacterium with plant cells.

PMID- 15494554
TI  - A conserved transcript pattern in response to a specialist and a generalist
      herbivore.
AB  - Transcript patterns elicited in response to attack reveal, at the molecular
      level, how plants respond to aggressors. These patterns are fashioned both by
      inflicted physical damage as well as by biological components displayed or
      released by the attacker. Different types of attacking organisms might therefore
      be expected to elicit different transcription programs in the host. Using a large
      scale DNA microarray, we characterized gene expression in damaged as well as in
      distal Arabidopsis thaliana leaves in response to the specialist insect, Pieris
      rapae. More than 100 insect-responsive genes potentially involved in defense were
      identified, including genes involved in pathogenesis, indole glucosinolate
      metabolism, detoxification and cell survival, and signal transduction. Of these
      114 genes, 111 were induced in Pieris feeding, and only three were repressed.
      Expression patterns in distal leaves were markedly similar to those of local
      leaves. Analysis of wild-type and jasmonate mutant plants, coupled with jasmonate
      treatment, showed that between 67 and 84% of Pieris-regulated gene expression was
      controlled, totally or in part, by the jasmonate pathway. This was correlated
      with increased larval performance on the coronatine insensitive1 glabrous1 (coi1
      1 gl1) mutant. Independent mutations in COI1 and GL1 led to a faster larval
      weight gain, but the gl1 mutation had relatively little effect on the expression
      of the insect-responsive genes examined. Finally, we compared transcript patterns
      in Arabidopis in response to larvae of the specialist P. rapae and to a
      generalist insect, Spodoptera littoralis. Surprisingly, given the complex nature
      of insect salivary components and reported differences between species, almost
      identical transcript profiles were observed. This study also provides a robustly
      characterized gene set for the further investigation of plant-insect interaction.

PMID- 15494555
TI  - Multiple genetic processes result in heterogeneous rates of evolution within the
      major cluster disease resistance genes in lettuce.
AB  - Resistance Gene Candidate2 (RGC2) genes belong to a large, highly duplicated
      family of nucleotide binding site-leucine rich repeat (NBS-LRR) encoding disease
      resistance genes located at a single locus in lettuce (Lactuca sativa). To
      investigate the genetic events occurring during the evolution of this locus,
      approximately 1.5- to 2-kb 3' fragments of 126 RGC2 genes from seven genotypes
      were sequenced from three species of Lactuca, and 107 additional RGC2 sequences
      were obtained from 40 wild accessions of Lactuca spp. The copy number of RGC2
      genes varied from 12 to 32 per genome in the seven genotypes studied extensively.
      LRR number varied from 40 to 47; most of this variation had resulted from 13
      events duplicating two to five LRRs because of unequal crossing-over within or
      between RGC2 genes at one of two recombination hot spots. Two types of RGC2 genes
      (Type I and Type II) were initially distinguished based on the pattern of
      sequence identities between their 3' regions. The existence of two types of RGC2
      genes was further supported by intron similarities, the frequency of sequence
      exchange, and their prevalence in natural populations. Type I genes are extensive
      chimeras caused by frequent sequence exchanges. Frequent sequence exchanges
      between Type I genes homogenized intron sequences, but not coding sequences, and
      obscured allelic/orthologous relationships. Sequencing of Type I genes from
      additional wild accessions confirmed the high frequency of sequence exchange and
      the presence of numerous chimeric RGC2 genes in nature. Unlike Type I genes, Type
      II genes exhibited infrequent sequence exchange between paralogous sequences.
      Type II genes from different genotype/species within the genus Lactuca showed
      obvious allelic/orthologous relationships. Trans-specific polymorphism was
      observed for different groups of orthologs, suggesting balancing selection.
      Unequal crossover, insertion/deletion, and point mutation events were distributed
      unequally through the gene. Different evolutionary forces have impacted different
      parts of the LRR.

PMID- 15494556
TI  - Processing of ATG8s, ubiquitin-like proteins, and their deconjugation by ATG4s
      are essential for plant autophagy.
AB  - Autophagy is an intracellular process for vacuolar degradation of cytoplasmic
      components. Thus far, plant autophagy has been studied primarily using
      morphological analyses. A recent genome-wide search revealed significant
      conservation among autophagy genes (ATGs) in yeast and plants. It has not been
      proved, however, that Arabidopsis thaliana ATG genes are required for plant
      autophagy. To evaluate this requirement, we examined the ubiquitination-like Atg8
      lipidation system, whose component genes are all found in the Arabidopsis genome.
      In Arabidopsis, all nine ATG8 genes and two ATG4 genes were expressed
      ubiquitously and were induced further by nitrogen starvation. To establish a
      system monitoring autophagy in whole plants, we generated transgenic Arabidopsis
      expressing each green fluorescent protein-ATG8 fusion (GFP-ATG8). In wild-type
      plants, GFP-ATG8s were observed as ring shapes in the cytoplasm and were
      delivered to vacuolar lumens under nitrogen-starved conditions. By contrast, in a
      T-DNA insertion double mutant of the ATG4s (atg4a4b-1), autophagosomes were not
      observed, and the GFP-ATG8s were not delivered to the vacuole under nitrogen
      starved conditions. In addition, we detected autophagic bodies in the vacuoles of
      wild-type roots but not in those of atg4a4b-1 in the presence of concanamycin A,
      a V-ATPase inhibitor. Biochemical analyses also provided evidence that autophagy
      in higher plants requires ATG proteins. The phenotypic analysis of atg4a4b-1
      indicated that plant autophagy contributes to the development of a root system
      under conditions of nutrient limitation.

PMID- 15494557
TI  - Beta-1,3 glucan sulfate, but not beta-1,3 glucan, induces the salicylic acid
      signaling pathway in tobacco and Arabidopsis.
AB  - Sulfate substituents naturally occurring in biomolecules, such as
      oligosaccharides and polysaccharides, can play a critical role in major
      physiological functions in plants and animals. We show that laminarin, a beta-1,3
      glucan with elicitor activity in tobacco (Nicotiana tabacum), becomes, after
      chemical sulfation, an inducer of the salicylic acid (SA) signaling pathway in
      tobacco and Arabidopsis thaliana. In tobacco cell suspensions, the oxidative
      burst induced by the laminarin sulfate PS3 was Ca2+ dependent but partially
      kinase independent, whereas laminarin triggered a strickly kinase-dependent
      oxidative burst. Cells treated with PS3 or laminarin remained fully responsive to
      a second application of laminarin or PS3, respectively, suggesting two distinct
      perception systems. In tobacco leaves, PS3, but not laminarin, caused electrolyte
      leakage and triggered scopoletin and SA accumulation. Expression of different
      families of Pathogenesis-Related (PR) proteins was analyzed in wild-type and
      mutant tobacco as well as in Arabidopsis. Laminarin induced expression of
      ethylene-dependent PR proteins, whereas PS3 triggered expression of ethylene- and
      SA-dependent PR proteins. In Arabidopsis, PS3-induced PR1 expression was also
      NPR1 (for nonexpressor of PR genes1) dependent. Structure-activity analysis
      revealed that (1) a minimum chain length is essential for biological activity of
      unsulfated as well as sulfated laminarin, (2) the sulfate residues are essential
      and cannot be replaced by other anionic groups, and (3) moderately sulfated beta
      1,3 glucans are active. In tobacco, PS3 and curdlan sulfate induced immunity
      against Tobacco mosaic virus infection, whereas laminarin induced only a weak
      resistance. The results open new routes to work out new molecules suitable for
      crop protection.

PMID- 15494558
TI  - ACCUMULATION OF PHOTOSYSTEM ONE1, a member of a novel gene family, is required
      for accumulation of [4Fe-4S] cluster-containing chloroplast complexes and antenna
      proteins.
AB  - To investigate the nuclear-controlled mechanisms of [4Fe-4S] cluster assembly in
      chloroplasts, we selected Arabidopsis thaliana mutants with a decreased content
      of photosystem I (PSI) containing three [4Fe-4S] clusters. One identified gene,
      ACCUMULATION OF PHOTOSYSTEM ONE1 (APO1), belongs to a previously unknown gene
      family with four defined groups (APO1 to APO4) only found in nuclear genomes of
      vascular plants. All homologs contain two related motifs of approximately 100
      amino acid residues that could potentially provide ligands for [4Fe-4S] clusters.
      APO1 is essentially required for photoautotrophic growth, and levels of PSI core
      subunits are below the limit of detection in the apo1 mutant. Unlike other
      Arabidopsis PSI mutants, apo1 fails to accumulate significant amounts of the
      outer antenna subunits of PSI and PSII and to form grana stacks. In particular,
      APO1 is essentially required for stable accumulation of other plastid-encoded and
      nuclear-encoded [4Fe-4S] cluster complexes within the chloroplast, whereas [2Fe
      2S] cluster-containing complexes appear to be unaffected. In vivo labeling
      experiments and analyses of polysome association suggest that translational
      elongation of the PSI transcripts psaA and psaB is specifically arrested in the
      mutant. Taken together, our findings suggest that APO1 is involved in the stable
      assembly of several [4Fe-4S] cluster-containing complexes of chloroplasts and
      interferes with translational events probably in association with plastid
      nucleoids.

PMID- 15494560
TI  - Coactivation of D1 and D2 dopamine receptors: in marriage, a case of his, hers,
      and theirs.
AB  - D1 and D2 dopamine receptors exert opposing effects on the same signaling pathway
      mediated by heterotrimeric GTP-binding proteins. D1 receptor activation
      positively affects adenylyl cyclase, and D2 receptor activation is either
      uncoupled from adenylyl cyclase or negatively affects it. These data suggest that
      coactivation of D1 and D2 receptors should produce opposite or competing
      intracellular signals through activation of separate D1- and D2-mediated
      signaling pathways. Unexpectedly, recent research suggests that D1 and D2
      receptor coactivation in cells that coexpress both receptors leads to the
      recruitment of a novel signaling pathway, involving phospholipase C (PLC)
      mediated calcium mobilization, that is distinct from the intracellular responses
      observed after stimulation of either dopamine receptor alone. This observation
      suggests that stimulation of D1 and D2 dopamine receptors has the potential to
      give rise to different intracellular signals depending on whether D1 or D2
      receptors are activated alone or together.

PMID- 15494561
TI  - Role of distinct NMDA receptor subtypes at central synapses.
AB  - Most excitatory synapses in the brain use the neurotransmitter glutamate to carry
      impulses between neurons. During fast transmission, glutamate usually activates a
      mixture of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) receptors in the postsynaptic cell. Experimental
      scrutiny of NMDARs provides insight into their involvement in excitatory synaptic
      transmission and related processes such as as synaptic plasticity, neural
      development, and pain perception. There is increasing awareness that subtle
      variation in NMDAR properties is imparted by specific receptor subunits, and
      recent studies have started to provide perspective into some of the discrete
      tasks carried out by individual receptor subtypes.

PMID- 15494562
TI  - AMPA receptor cycling in the synapse.
AB  - Ionotropic glutamate receptors (GluRs) are involved in mediating signaling in
      response to synaptic activity. In addition to converting the chemical signal
      released from the presynaptic terminal to an electrical response in the
      postsynaptic neuron, these receptors are critically involved in activity
      dependent, long-term changes in synaptic strength and, therefore, are central to
      processes thought to underlie learning and memory. The animation provides an
      interactive illustration of how activity-dependent changes in the glutamate
      receptor composition and numbers at the synapse may contribute to synaptic
      plasticity.

PMID- 15494563
TI  - A piece of my mind. The secret.

PMID- 15494564
TI  - Polio eradication goal still elusive.

PMID- 15494565
TI  - Road to recovery for cocaine users can start in primary care setting.

PMID- 15494566
TI  - FDA OKs nonprescription defibrillators.

PMID- 15494573
TI  - Author! Author!

PMID- 15494574
TI  - Author! Author!

PMID- 15494575
TI  - Chlorthalidone vs other low-dose diuretics.

PMID- 15494576
TI  - Author! Author!

PMID- 15494577
TI  - HER-2 testing in breast cancer.

PMID- 15494578
TI  - Tramadol abuse and dependence among physicians.

PMID- 15494579
TI  - Comparison of MRI and CT for detection of acute intracerebral hemorrhage.
AB  - CONTEXT: Noncontrast computed tomography (CT) is the standard brain imaging study
      for the initial evaluation of patients with acute stroke symptoms. Multimodal
      magnetic resonance imaging (MRI) has been proposed as an alternative to CT in the
      emergency stroke setting. However, the accuracy of MRI relative to CT for the
      detection of hyperacute intracerebral hemorrhage has not been demonstrated.
      OBJECTIVE: To compare the accuracy of MRI and CT for detection of acute
      intracerebral hemorrhage in patients presenting with acute focal stroke symptoms.
      DESIGN, SETTING, AND PATIENTS: A prospective, multicenter study was performed at
      2 stroke centers (UCLA Medical Center and Suburban Hospital, Bethesda, Md),
      between October 2000 and February 2003. Patients presenting with focal stroke
      symptoms within 6 hours of onset underwent brain MRI followed by noncontrast CT.
      MAIN OUTCOME MEASURES: Acute intracerebral hemorrhage and any intracerebral
      hemorrhage diagnosed on gradient recalled echo (GRE) MRI and CT scans by a
      consensus of 4 blinded readers. RESULTS: The study was stopped early, after 200
      patients were enrolled, when it became apparent at the time of an unplanned
      interim analysis that MRI was detecting cases of hemorrhagic transformation not
      detected by CT. For the diagnosis of any hemorrhage, MRI was positive in 71
      patients with CT positive in 29 (P<.001). For the diagnosis of acute hemorrhage,
      MRI and CT were equivalent (96% concordance). Acute hemorrhage was diagnosed in
      25 patients on both MRI and CT. In 4 other patients, acute hemorrhage was present
      on MRI but not on the corresponding CT--each of these 4 cases was interpreted as
      hemorrhagic transformation of an ischemic infarct. In 3 patients, regions
      interpreted as acute hemorrhage on CT were interpreted as chronic hemorrhage on
      MRI. In 1 patient, subarachnoid hemorrhage was diagnosed on CT but not on MRI. In
      49 patients, chronic hemorrhage, most often microbleeds, was visualized on MRI
      but not on CT. CONCLUSION: MRI may be as accurate as CT for the detection of
      acute hemorrhage in patients presenting with acute focal stroke symptoms and is
      more accurate than CT for the detection of chronic intracerebral hemorrhage.

PMID- 15494580
TI  - Predictors of in-hospital mortality in patients with acute ischemic stroke
      treated with thrombolytic therapy.
AB  - CONTEXT: Data are limited regarding the risks and benefits of thrombolytic
      therapy for acute ischemic stroke outside of clinical trials. OBJECTIVE: To
      investigate predictors of in-hospital mortality in patients with ischemic stroke
      treated with intravenous tissue plasminogen activator (tPA) within a pooled
      analysis of large German stroke registers. DESIGN AND SETTING: Prospective,
      observational cohort study conducted at 225 community and academic hospitals
      throughout Germany cooperating within the German Stroke Registers Study Group.
      PATIENTS: A total of 1658 patients with acute ischemic stroke who were admitted
      to study hospitals between 2000 and 2002 and were treated with tPA. MAIN OUTCOME
      MEASURE: In-hospital mortality. RESULTS: One hundred sixty-six patients (10%) who
      received tPA died during hospitalization, with 67.5% of these deaths occurring
      within 7 days. Factors predicting in-hospital death after tPA use were older age
      (for each 10-year increment in age, adjusted odds ratio [OR], 1.6; 95% confidence
      interval [CI], 1.3-1.9) and altered level of consciousness (adjusted OR, 3.4; 95%
      CI, 2.4-4.7). The overall rate of symptomatic intracranial hemorrhage was 7.1%
      and increased with age. One or more serious complications was observed in 27.2%
      of all patients and in 83.9% of patients who died after tPA treatment. An inverse
      relation between the number of patients treated with tPA in the respective
      hospital and the risk of in-hospital death was observed (adjusted OR, 0.97; 95%
      CI, 0.96-0.99 for each additional patient treated with tPA per year). CONCLUSION:
      In patients with ischemic stroke who are treated with tPA, disturbances of
      consciousness and increasing age are associated with increased in-hospital
      mortality.

PMID- 15494581
TI  - Lack of improvement in patients with acute stroke after treatment with
      thrombolytic therapy: predictors and association with outcome.
AB  - CONTEXT: The focus of thrombolytic therapy in acute stroke has been on favorable
      outcome at 3 months. Few studies have analyzed outcome at 24 hours. An early and
      reliable prediction of poor outcome has implications for clinical management and
      discharge planning. OBJECTIVE: To evaluate predictors of lack of improvement at
      24 hours after receiving alteplase and their relationship with poor outcome at 3
      months. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort of consecutive
      patients with acute stroke who received alteplase and were admitted to a
      university hospital from January 1999 to March 2003. Participants were recruited
      from 2 academic centers in a major city in Ontario and 33 affiliated hospitals
      from 7 counties. MAIN OUTCOME MEASURES: Lack of improvement defined as a
      difference between the National Institutes of Health Stroke Scale score at
      baseline and at 24 hours of 3 points or less. Poor outcome at 3 months defined by
      a modified Rankin Scale score of 3 to 5 or death. RESULTS: Among 216 patients
      with acute stroke who were treated with alteplase, 111 (51.4%) had a lack of
      improvement at 24 hours. After adjusting for age, sex, and stroke severity,
      baseline glucose level on admission (odds ratio [OR] 2.89; 95% confidence
      interval [CI], 1.40-5.99 for a glucose level >144 mg/dL [>8 mmol/L]), cortical
      involvement (OR, 2.66; 95% CI, 1.36-5.20), and time to treatment (OR, 1.01; 95%
      CI, 1.0-1.02 for each 1 minute increase in time to treatment) were independent
      predictors of lack of improvement. At 3 months, 43 patients (20.2%) had died; of
      the 170 survivors, 75 patients (44%) had poor outcomes. After adjusting for age,
      sex, and stroke severity, lack of improvement at 24 hours was an independent
      predictor of poor outcome (OR, 12.9; 95%CI, 5.7-29.6) and death (OR, 7.5; 95% CI,
      2.9-19.6). Patients with a lack of improvement had longer lengths of
      hospitalization (14.5 vs 9.6 days; P = .02). CONCLUSIONS: Among patients with
      acute stroke treated with thrombolytic therapy, lack of improvement at 24 hours
      is associated with poor outcome and death at 3 months. Elevated glucose level,
      time to thrombolytic therapy, and cortical involvement were predictors of lack of
      improvement.

PMID- 15494582
TI  - Extracranial thrombotically active carotid plaque as a risk factor for ischemic
      stroke.
AB  - CONTEXT: Recent studies suggest that factors other than the degree of carotid
      stenosis are involved in ischemic stroke pathogenesis, especially modifications
      of plaque composition and related complications. OBJECTIVE: To examine the role
      of carotid plaque rupture and thrombosis in ischemic stroke pathogenesis in
      patients undergoing carotid endarterectomy, excluding those with possible cardiac
      embolization or with severe stenosis of the circle of Willis. DESIGN, SETTING,
      AND PATIENTS: A total of 269 carotid plaques selected from an Interinstitutional
      Carotid Tissue Bank were studied by histology after surgical endarterectomy
      between January 1995 and December 2002. A total of 96 plaques were from patients
      with ipsilateral major stroke, 91 plaques from patients with transient ischemic
      attack (TIA), and 82 plaques from patients without symptoms. MAIN OUTCOME
      MEASURES: Differences in the frequency of thrombosis, cap rupture, cap erosion,
      inflammatory infiltrate, and major cardiovascular risk factors between study
      groups. RESULTS: A thrombotically active carotid plaque associated with high
      inflammatory infiltrate was observed in 71 (74.0%) of 96 patients with
      ipsilateral major stroke (and in all 32 plaques from patients operated within 2
      months of symptom onset) compared with 32 (35.2%) of 91 patients with TIA (P <
      .001) or 12 (14.6%) of 82 patients who were without symptoms (P < .001). In
      addition, a fresh thrombus was observed in 53.8% of patients with stroke operated
      13 to 24 months after the cerebrovascular event. An acute thrombus was associated
      with cap rupture in 64 (90.1%) of 71 thrombosed plaques from patients with stroke
      and with cap erosion in the remaining 7 cases (9.9%). Ruptured plaques of
      patients affected by stroke were characterized by the presence of a more severe
      inflammatory infiltrate, constituted by monocytes, macrophages, and T lymphocyte
      cells compared with that observed in the TIA and asymptomatic groups (P = .001).
      There was no significant difference between groups in major cardiovascular risk
      factors. CONCLUSION: These results demonstrate a major role of carotid thrombosis
      and inflammation in ischemic stroke in patients affected by carotid
      atherosclerotic disease.

PMID- 15494583
TI  - Repetitive bilateral arm training and motor cortex activation in chronic stroke:
      a randomized controlled trial.
AB  - CONTEXT: Reorganization in central motor networks occurs during early recovery
      from hemiparetic stroke. In chronic stroke survivors, specific rehabilitation
      therapy can improve upper extremity function. OBJECTIVE: To test the hypothesis
      that in patients who have chronic motor impairment following stroke, specific
      rehabilitation therapy that improves arm function is associated with
      reorganization of cortical networks. DESIGN, SETTING, AND PATIENTS: A randomized
      controlled clinical trial conducted in a US ambulatory rehabilitation program
      with 21 patients (median [IQR], 50.3 [34.8-77.3] months after unilateral stroke).
      Data were collected between 2001 and 2004. INTERVENTIONS: Patients were randomly
      assigned to bilateral arm training with rhythmic auditory cueing (BATRAC) (n = 9)
      or standardized dose-matched therapeutic exercises (DMTE) (n = 12). Both were
      conducted for 1 hour, 3 times a week, for 6 weeks. MAIN OUTCOME MEASURES: Within
      2 weeks before and after the intervention, brain activation during elbow movement
      assessed by functional magnetic resonance imaging (fMRI) and functional outcome
      assessed using arm function scores. RESULTS: Patients in the BATRAC group but not
      in the DMTE group increased hemispheric activation during paretic arm movement (P
      = .03). Changes in activation were observed in the contralesional cerebrum and
      ipsilesional cerebellum (P = .009). BATRAC was associated with significant
      increases in activation in precentral (P<.001) and postcentral gyri (P = .03) and
      the cerebellum (P<.001), although 3 BATRAC patients showed no fMRI changes.
      Considering all patients, there were no differences in functional outcome between
      groups. When only BATRAC patients with fMRI response were included (n = 6),
      BATRAC improved arm function more than DMTE did (P = .02). CONCLUSIONS: These
      preliminary findings suggest that BATRAC induces reorganization in contralesional
      motor networks and provide biological plausibility for repetitive bilateral
      training as a potential therapy for upper extremity rehabilitation in hemiparetic
      stroke.

PMID- 15494584
TI  - Long-term outcome after intravenous thrombolysis of basilar artery occlusion.
AB  - CONTEXT: Basilar artery occlusion (BAO) is an infrequent disease with high
      morbidity and mortality. Intra-arterial thrombolysis is advocated for treatment
      but is limited to use at specialized centers. OBJECTIVE: To evaluate outcomes for
      patients with BAO treated with intravenous thrombolytic therapy. DESIGN, SETTING,
      AND PARTICIPANTS: During 1995 to 2003, 50 consecutive patients with
      angiographically proven BAO were treated according to an institutional therapy
      protocol based on intravenous thrombolysis with recombinant tissue plasminogen
      activator (alteplase). Patients were treated at an urban university teaching
      hospital receiving all patients with ischemic stroke who were considered for
      thrombolysis in a catchment area of 1.5 million inhabitants in Helsinki, Finland.
      INTERVENTION: Intravenous administration of alteplase (0.9 mg/kg) during a 1-hour
      infusion. MAIN OUTCOME MEASURES: Basilar artery recanalization determined by
      magnetic resonance angiography and clinical outcomes at 3 months and at 1 year or
      longer determined by modified Rankin Scale and Barthel Index scores. RESULTS:
      Recanalization was studied in 43 patients and verified in 26 (52%) of all
      patients. By 3 months, 20 patients (40%) had died while 11 had good outcomes
      (modified Rankin Scale score, 0-2); 12 (24%) reached independence in activities
      of daily living (Barthel Index score, 95-100), and 6 (16%) were severely disabled
      (Barthel Index score, 0-50). In the long term (median follow-up 2.8 years), 15
      patients (30%) reached good outcomes (modified Rankin Scale score, 0-2) while 23
      (46%) died. CONCLUSIONS: Intravenous administration of alteplase for patients
      with BAO appears to be associated with rates of survival, recanalization, and
      independent functional outcome comparable with those reported with endovascular
      approaches. These data suggest that a randomized trial is needed to compare these
      approaches for treatment of BAO.

PMID- 15494585
TI  - Oral antiplatelet therapy in cerebrovascular disease, coronary artery disease,
      and peripheral arterial disease.
AB  - CONTEXT: Atherothrombosis is a pathophysiologic process that results in clinical
      ischemic events affecting the cerebral, coronary, and peripheral arterial
      circulation. Antiplatelet agents, used alone or in combination, are effective in
      preventing recurrent vascular events among individuals with established vascular
      disease. OBJECTIVE: To summarize the current state of evidence regarding oral
      antiplatelet treatment in patients with cerebrovascular disease, coronary artery
      disease (CAD), and peripheral arterial disease. EVIDENCE ACQUISITION: Using the
      key terms acute coronary syndrome, atherothrombosis, ischemic stroke, myocardial
      infarction, MI, peripheral arterial disease, TIA, transient ischemic attack,
      unstable angina,aspirin,ticlopidine,dipyridamole, and clopidogrel, we searched
      the MEDLINE database as well as the trial register of the Cochrane Groups to
      identify studies published from 1960 to August 2004. We manually searched
      journals and abstract booklets; scrutinized reference lists of trials and review
      articles; and reviewed meta-analyses, scientific statements, and guidelines from
      official societies. EVIDENCE SYNTHESIS: Appropriate oral first-line antiplatelet
      therapy is aspirin for individuals with ST-segment elevation myocardial
      infarction; aspirin or clopidogrel for those with TIA or stroke, chronic stable
      angina, or peripheral arterial disease; and aspirin combined with clopidogrel for
      those with non-ST-segment elevation acute coronary syndrome. Aspirin combined
      with dipyridamole is a possible alternative for patients who experience a first
      episode of TIA or stroke in the absence of clinically apparent CAD. Although
      ticlopidine has been shown to be of benefit in various vascular conditions, its
      adverse-effect profile has limited its use. CONCLUSIONS: Aspirin, ticlopidine,
      clopidogrel, aspirin combined with clopidogrel, and aspirin combined with
      dipyridamole are effective in preventing recurrent vascular events among various
      subgroups of patients with vascular disease. Current clinical trial evidence
      favors the use of aspirin or clopidogrel as first-line agents for the majority of
      patients with vascular disease. Clinical trials evaluating combination
      antiplatelet therapies will direct future practice.

PMID- 15494586
TI  - Antiplatelet therapy in non-ST-segment elevation acute coronary syndromes.
AB  - Acute coronary syndromes are a frequent cause of hospital admission for patients
      with coronary artery disease. The pathophysiology of acute coronary syndromes
      often involves plaque rupture or fissure with platelet aggregation. Recognition
      of the importance of platelet aggregation resulted in several large randomized
      trials testing 3 types of platelet antagonists, aspirin, glycoprotein IIb/IIIa
      inhibitors, and adenosine diphosphate inhibitors. A thorough understanding of the
      data, risks, and benefits of these therapies is important to optimize treatment
      of the patient with an acute coronary syndrome. Recognition that there is a great
      deal of interpatient variability in response to these antiplatelet therapies
      highlights the need for future research in this area.

PMID- 15494587
TI  - Treatment of acute stroke: still struggling.

PMID- 15494588
TI  - Stroke prevention: optimizing the response to a common threat.

PMID- 15494589
TI  - Emerging infectious diseases: a clear and present danger to humanity.

PMID- 15494591
TI  - JAMA patient page. Hemorrhagic stroke.

PMID- 15494592
TI  - Ductal lavage for early detection--what doesn't come out in the wash.

PMID- 15494593
TI  - Breast cancer screening comes full circle.

PMID- 15494594
TI  - The Gompertzian view: Norton honored for role in establishing cancer treatment
      approach.

PMID- 15494595
TI  - Presidential candidates weigh in on health issues.

PMID- 15494596
TI  - Accelerated approval seen as triumph and roadblock for cancer drugs.

PMID- 15494597
TI  - Stat bite: Incidence of in situ and invasive breast cancer by age, 1975-2001.

PMID- 15494598
TI  - Resveratrol may be a powerful cancer-fighting ally.

PMID- 15494599
TI  - Formation of pan-European groups buoys cause of patient advocates.

PMID- 15494600
TI  - Accelerated approval of oncology products: a decade of experience.
AB  - We review the regulatory history of the accelerated approval process and
      summarize the U.S. Food and Drug Administration experience with accelerated
      approvals in oncology. The accelerated approval regulations, promulgated in 1992,
      allow approval of drugs for serious or life-threatening diseases on the basis of
      a surrogate endpoint that is reasonably likely to predict clinical benefit, such
      as survival or symptom benefit, pending completion of studies designed to confirm
      clinical benefit, referred to as phase 4 commitments, which are required to be
      conducted with due diligence. From 1992 to 2004, 22 applications involving
      anticancer drugs or biologics were approved. Of these 22 applications,
      accelerated approval was granted to 15 on the basis of findings from studies
      without an active comparator (i.e., single-arm studies or studies comparing two
      dose levels) and to the remaining seven on the basis of one or more randomized
      studies. Of the 22 approved applications, six (i.e., applications for
      dexrazoxane, irinotecan, capecitabine, docetaxel, imatinib mesylate, and
      oxaliplatin) have had one or more indications converted to regular approval. This
      review reports information that was presented at an Oncologic Drugs Advisory
      Committee meeting held in March 2003; it also presents a discussion of
      accelerated approval study designs, the study populations evaluated in the
      accelerated approval and confirmatory settings, and the integration of
      accelerated approval into a comprehensive drug development plan.

PMID- 15494601
TI  - Ductal lavage findings in women with known breast cancer undergoing mastectomy.
AB  - BACKGROUND: Ductal lavage has the potential to detect cancer by sampling breast
      epithelium in asymptomatic high-risk women. To assess the utility of ductal
      lavage as a cancer diagnostic test, we investigated the association between
      ductal lavage cytologic findings and histologic findings in women with known
      breast cancer undergoing mastectomy. METHODS: Ductal lavage was performed in the
      operating room before mastectomy on 44 breasts from 32 women with known cancer
      and on eight breasts from seven women undergoing prophylactic mastectomy, two
      with occult malignancy. If the ductal lavage sample from one or more ducts
      contained enough epithelial cells for a cytologic diagnosis, lavaged ducts were
      injected with a mixture of colored dye, gelatin, and a radiographic contrast
      compound after mastectomy, and breast tissue was radiographed and sectioned.
      Histologic findings in ducts with and without dye were recorded. Associations
      between cytologic results and histologic results were examined by univariate and
      multivariable analyses. RESULTS: At least one duct was lavaged in 36 breasts
      (mean = 1.4 ducts per breast); all histologic and cytologic procedures were
      completed in 28 breasts and in 39 ducts. Markedly atypical or malignant cytology
      was found in five cancer-containing breasts. In 39 ducts with complete cytologic
      and histologic data and when marked atypia or malignant cells defined a positive
      cytologic test, sensitivity was 43% (95% confidence interval [CI] = 23% to 72%),
      specificity was 96% (95% CI = 86% to 100%), and accuracy was 77% (95% CI = 63% to
      89%). When mild or marked atypia or malignant cells defined a positive cytologic
      test, sensitivity was 79% (95% CI = 57% to 96%), specificity was 64% (95% CI =
      46% to 83%), and accuracy was 69% (95% CI = 55% to 83%). When all 31
      cytologically evaluable breasts were analyzed, sensitivity was 17% (95% CI = 7%
      to 35%), specificity was 100% (95% CI = 5% to 100%), and accuracy was 19% (95% CI
      = 9% to 38%). CONCLUSION: In breasts with cancer, ductal lavage appears to have
      low sensitivity and high specificity for cancer detection, possibly because
      cancer-containing ducts fail to yield fluid or have benign or mildly atypical
      cytology.

PMID- 15494602
TI  - Reason for late-stage breast cancer: absence of screening or detection, or
      breakdown in follow-up?
AB  - BACKGROUND: Mammography screening increases the detection of early-stage breast
      cancers. Therefore, implementing screening should reduce the percentage of women
      who are diagnosed with late-stage disease. However, despite high national
      mammography screening rates, late-stage breast cancers still occur, possibly
      because of failures in screening implementation. METHODS: Using data from seven
      health care plans that included 1.5 million women aged 50 years or older, we
      conducted retrospective reviews of chart and automated data for 3 years before
      1995-1999 diagnoses of late-stage (metastatic and/or tumor size > or =3 cm; case
      subjects, n = 1347) and early-stage breast cancers (control subjects, n = 1347).
      We categorized the earliest screening mammogram during the period 13-36 months
      before diagnosis as none (absence of screening), negative (absence of detection),
      or positive (potential breakdown in follow-up). We compared the proportion of
      case and control subjects in each category of screening implementation and
      estimated the likelihood (odds ratio [OR] with 95% confidence intervals [CIs]) of
      late-stage breast cancer. We also evaluated demographic characteristics
      associated with absence of screening in women with late-stage disease. All
      statistical tests were two-sided. RESULTS: Absence of screening, absence of
      detection, and potential breakdown in follow-up were distributed differently
      among case (52.1%, 39.5%, and 8.4%, respectively) and control subjects (34.4%,
      56.9%, and 8.8%, respectively) (P = .03). Among all women, the odds of having
      late-stage cancer were higher among women with an absence of screening (OR =
      2.17, 95% CI = 1.84 to 2.56; P<.001). Among case patients, women were more likely
      to be in the absence-of-screening group if they were aged 75 years or older (OR =
      2.77, 95% CI = 2.10 to 3.65), unmarried (OR = 1.78, 95% CI = 1.41 to 2.24), or
      without a family history of breast cancer (OR = 1.84, 95% CI = 1.45 to 2.34). A
      higher proportion of women from census blocks with less education (58.5% versus
      49.4%; P = .003) or lower median annual income (54.4% versus 42.9%; P = .004)
      were in the absence-of-screening category compared with the proportion for the
      other two categories combined. CONCLUSIONS: To reduce late-stage breast cancer
      occurrence, reaching unscreened women, including elderly, unmarried, low-income,
      and less educated women, should be made a top priority for screening
      implementation.

PMID- 15494603
TI  - Stroke risk and tamoxifen therapy for breast cancer.
AB  - BACKGROUND: Tamoxifen, which is used widely to treat, and increasingly to
      prevent, breast cancer, has been associated with increased risk of stroke. We
      assessed the impact of tamoxifen treatment for breast cancer on the risk of
      stroke, considering dose, duration, and recency of use of tamoxifen and known
      stroke risk factors. METHODS: We conducted a nested case-control study of stroke
      after breast cancer among female Los Angeles County residents enrolled in a large
      health maintenance organization when diagnosed with breast cancer between January
      1, 1980, and July 1, 2000. We obtained information on breast cancer treatment and
      stroke risk factors through medical record review and telephone interviews. The
      association (odds ratio [OR] and 95% confidence interval [CI]) between tamoxifen
      and stroke risk was determined by using a conditional logistic regression model,
      adjusting for menopausal status and history of hypertension and diabetes. All
      statistical tests were two-sided. RESULTS: Of 11 045 women with breast cancer,
      179 met stroke eligibility criteria and were individually matched to two stroke
      free control subjects with breast cancer on age and year of breast cancer
      diagnosis. The mean age at breast cancer diagnosis was 66.6 years (standard
      deviation [SD] = 12.3 years), and the mean at-risk period (i.e., the time between
      breast cancer diagnosis and first stroke or comparable time period for control
      subjects) was 5.7 years (SD = 4.5 years). Tamoxifen use was not associated with
      risk of stroke, either overall (OR = 1.0, 95% CI = 0.6 to 1.6) or in subgroups
      defined by duration, dose, or recency of use. Chemotherapy, but not a specific
      chemotherapy regimen, was associated with an increased risk of stroke, regardless
      of tamoxifen use (no tamoxifen use, OR = 2.8, 95% CI = 1.3 to 6.3; tamoxifen use
      OR = 2.2, 95% CI = 1.2 to 4.1). CONCLUSIONS: Tamoxifen use is not associated with
      increased stroke risk. Further exploration of possible increased stroke risk
      following chemotherapy treatment for breast cancer is needed.

PMID- 15494604
TI  - Effects of insulin-like growth factor binding protein-3 and farnesyltransferase
      inhibitor SCH66336 on Akt expression and apoptosis in non-small-cell lung cancer
      cells.
AB  - BACKGROUND: Overexpression of insulin-like growth factor binding protein-3 (IGFBP
      3) induces apoptosis in non-small-cell lung cancer (NSCLC) cells in vitro and in
      vivo. However, Ras-mediated signaling pathways could develop resistance to
      apoptotic activities of IGFBP-3 in NSCLC cells. We thus evaluated the therapeutic
      potential of the combination of IGFBP-3 and SCH66336, a farnesyltransferase
      inhibitor that blocks Ras activation, in NSCLC cell lines. METHODS: The effects
      of the combination of adenoviral IGFBP-3 (Ad-IGFBP3) and SCH66336 on
      proliferation and apoptosis of NSCLC cell lines (H1299, H596, A549, H460, H358,
      H322, and H226B) were assessed in vitro and in vivo by using the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, a flow
      cytometry-based terminal deoxynucleotidyl transferase deoxyuridine triphosphate
      nick-end labeling assay, western blot analyses, and an NSCLC xenograft tumor
      model. The specific effects of Ad-IGFBP 3 and SCH66336 on mitogen-activated
      protein kinase and Akt were assessed by using adenoviral vectors that express
      constitutively active MEK1 or constitutively active Akt. Synergy was assessed by
      median effect analysis. RESULTS: The combination of Ad-IGFBP3 and SCH66336 had
      synergistic antiproliferative effects in five cell lines (H1299, H596, A549,
      H460, and H322). Antiproliferative effects were accompanied by increased
      apoptosis in H460 cells in vitro. Overexpression of a constitutively active Akt
      but not a constitutively active MEK-1 rescued H460 cells from apoptosis induced
      by single or combined treatment of Ad-IGFBP3 and SCH66336. In H1299 tumor
      xenografts, Ad-IGFBP3 and SCH66336 was associated with decreased tumor volume,
      increased apoptosis, and decreased Akt levels. CONCLUSIONS: The combination of Ad
      IGFBP3 and SCH66336 decreased Akt expression and increased apoptosis in NSCLC
      cells in vitro and in vivo. Simultaneous treatment with IGFBP-3 and SCH66336 may
      have the potential to be an effective therapeutic strategy in NSCLC.

PMID- 15494605
TI  - Birth weight and risk for childhood leukemia in Denmark, Sweden, Norway, and
      Iceland.
AB  - BACKGROUND: Compelling evidence suggests that childhood leukemia often originates
      in utero. Birth weight is one of the few pregnancy-related risk factors that has
      been associated with leukemia risk, but the association has remained poorly
      characterized. We conducted a population-based case-control study in Denmark,
      Sweden, Norway, and Iceland to investigate the association between birth weight
      (and other birth characteristics) and the risk of childhood leukemia. METHODS:
      Overall, 1905 children (aged 0-14 years) with acute lymphoblastic leukemia (ALL)
      and 299 children with acute myeloid leukemia (AML) diagnosed between January 1,
      1984, and December 31, 1999, were identified in the Nordic Society of Paediatric
      Haematology and Oncology acute leukemia database. Each case patient was matched
      to five population control subjects (n = 10745) on nationality, age, and sex. All
      live-born siblings of case patients (n = 3812) and control subjects (n = 17,937)
      were also identified in population registers. Information on birth weight and
      gestational age at birth was ascertained from the national Medical Birth
      Registers. The association between various birth characteristics and leukemia
      risk was assessed by conditional logistic regression. All statistical tests were
      two-sided. RESULTS: Risk of ALL overall was statistically significantly
      associated with birth weight (odds ratio [OR] = 1.26 per 1-kg increase in birth
      weight, 95% confidence interval [CI] = 1.13 to 1.41). The association was similar
      for B- and T-lineage ALL and across all diagnostic ages (0-14 years). However,
      children with ALL did not weigh more at birth than their siblings. Statistically
      significantly reduced risks of B-precursor ALL were observed with increasing
      position in the birth order (OR = 0.90 per position increase, 95% CI = 0.84 to
      0.96) and increasing gestational age (OR = 0.87 per 2-week increase in
      gestational age, 95% CI = 0.81 to 0.94). Risk of AML did not vary monotonically
      with birth weight, and low birth weight (<1500 g [i.e., 3.3 pounds]) was
      associated with the highest risk. CONCLUSION: Our results are compatible with the
      hypothesis that a high birth weight is associated with an increased risk of ALL.

PMID- 15494606
TI  - Treatment of accidental intrathecal methotrexate overdose with intrathecal
      carboxypeptidase G2.
AB  - The bacterial enzyme carboxypeptidase G2 (CPDG2) rapidly hydrolyzes methotrexate
      to inactive metabolites. We administered recombinant CPDG2 (2000 U) intrathecally
      to seven cancer patients 3 to 9 hours after they had received an accidental
      overdose of intrathecal methotrexate (median dose = 364 mg; range = 155-600 mg).
      Four of the seven patients had cerebrospinal fluid (CSF) exchange to remove
      methotrexate before CPDG2 administration. Immediate symptoms of the methotrexate
      overdoses included seizures (n = 5), coma (n = 2), and cardiopulmonary compromise
      (n = 2). Before CPDG2 administration, the median concentrations of methotrexate
      in CSF were 264 microM (range = 97-510 microM) among patients who had CSF
      exchange and 8050 microM (range = 2439-16 500 microM) among patients who did not.
      After intrathecal CPDG2 administration, methotrexate concentrations in CSF
      declined by more than 98%. All patients recovered completely from the intrathecal
      methotrexate overdose except for two patients who had memory impairments.
      Antibodies to CPDG2 were not detected in plasma after treatment with intrathecal
      CPDG2. Intrathecal CPDG2 is well tolerated, rapidly decreases CSF methotrexate
      concentrations, and appears to be efficacious for treating accidental intrathecal
      methotrexate overdoses.

PMID- 15494607
TI  - Re: Are women more susceptible to lung cancer?

PMID- 15494608
TI  - Abrogation of oxidative stress improves insulin sensitivity in the Ren-2 rat
      model of tissue angiotensin II overexpression.
AB  - To evaluate the role of renin-angiotensin system (RAS)-mediated oxidative stress
      in insulin resistance (IR), we compared the effects of the angiotensin II (ANG
      II) receptor blocker (ARB) valsartan and a superoxide dismutase (SOD) mimetic,
      tempol, on whole body glucose tolerance and soleus muscle insulin-stimulated
      glucose uptake in transgenic hypertensive TG(mREN-2)27 (Ren-2) rats. Ren-2 rats
      and Sprague-Dawley (SD) controls were given valsartan (30 mg/kg) or tempol (1
      mmol/l) in their drinking water for 21 days. IR was measured by glucose tolerance
      testing (1 g/kg glucose ip). IR index (AUC(glucose) x AUC(insulin)) was
      significantly higher in the Ren-2 animals compared with SD controls (30.5 +/- 7.0
      x 10(6) arbitrary units in Ren-2 vs. 10.2 +/- 2.4 x 10(6) in SD, P < 0.01). Both
      valsartan and tempol treatment normalized Ren-2 IR index. Compared with SD
      controls (100%), there was a significant increase in superoxide anion production
      (measured by lucigenin-enhanced chemiluminescence) in soleus muscles of Ren-2
      rats (133 +/- 15%). However, superoxide production was reduced in both valsartan-
      and tempol-treated (85 +/- 22% and 59 +/- 12%, respectively) Ren-2 rats. Insulin
      (INS)-mediated 2-deoxyglucose (2-DG) uptake (%SD basal levels) was substantially
      lower in Ren-2 rat soleus muscle compared with SD (Ren-2 + INS = 110 +/- 3% vs.
      SD + INS = 206 +/- 12%, P < 0.05). However, Ren-2 rats treated with valsartan or
      tempol exhibited a significant increase in insulin-mediated 2-DG uptake compared
      with untreated transgenic animals. Improvements in skeletal muscle insulin
      dependent glucose uptake and whole body IR in rats overexpressing ANG II by ARB
      or SOD mimetic indicate that oxidative stress plays an important role in ANG II
      mediated insulin resistance.

PMID- 15494609
TI  - Effects of diabetes and recurrent hypoglycemia on the regulation of the
      sympathoadrenal system and hypothalamo-pituitary-adrenal axis.
AB  - Epinephrine, norepinephrine, and corticosterone responses to hypoglycemia are
      impaired in diabetic rats. Recurrent hypoglycemia further diminishes epinephrine
      responses. This study examined the sympathoadrenal system and hypothalamo
      pituitary-adrenal axis for molecular adaptations underlying these defects. Groups
      were normal (N) and diabetic (D) rats and diabetic rats exposed to 4 days of 2
      episodes/day of hyperinsulinemic hypoglycemia (D-hypo) or hyperinsulinemic
      hyperglycemia (D-hyper). D-hypo and D-hyper rats differentiated effects of
      hypoglycemia and hyperinsulinemia. Adrenal tyrosine hydroxylase (TH) mRNA was
      reduced (P < 0.05 vs. N) 25% in all diabetic groups. Remarkably, mRNA for
      phenylethanolamine N-methyltransferase (PNMT), which converts norepinephrine to
      epinephrine, was reduced (P < 0.05 vs. all) 40% only in D-hypo rats.
      Paradoxically, dopamine beta-hydroxylase mRNA was elevated (P < 0.05 vs. D, D
      hyper) in D-hypo rats. Hippocampal mineralocorticoid receptor (MR) mRNA was
      increased (P < 0.05 vs. N) in all diabetic groups. Hippocampal glucocorticoid
      receptor (GR), hypothalamic paraventricular nucleus (PVN) GR and corticotropin
      releasing hormone (CRH), and pituitary GR and proopiomelanocortin (POMC) mRNA
      levels did not differ. We conclude that blunted corticosterone responses to
      hypoglycemia in diabetic rats are not due to altered basal expression of GR, CRH,
      and POMC in the hippocampus, PVN, and pituitary. The corticosterone defect also
      does not appear to be due to increased hippocampal MR, since we have reported
      normalized corticosterone responses in D-hypo and D-hyper rats. Furthermore,
      impaired epinephrine counterregulation in diabetes is associated with reduced
      adrenal TH mRNA, whereas the additional epinephrine defect after recurrent
      hypoglycemia is associated with decreases in both TH and PNMT mRNA.

PMID- 15494610
TI  - Mechanisms of membrane estrogen receptor-alpha-mediated rapid stimulation of Ca2+
      levels and prolactin release in a pituitary cell line.
AB  - The role of membrane estrogen receptor-alpha (mERalpha) in rapid nongenomic
      responses to 17beta-estradiol (E(2)) was tested in sublines of GH3/B6 rat
      prolactinoma cells selected for high (GH3/B6/F10) and low (GH3/B6/D9) mERalpha
      expression. E(2) elicited rapid, concentration-dependent intracellular Ca(2+)
      concentration ([Ca(2+)](i)) increases in the F10 subline. Lack of inhibition by
      thapsigargin depletion of intracellular Ca(2+) pools, together with abrogation of
      the response in Ca(2+)-free medium, suggested an extracellular source of Ca(2+)
      for this response. The participation of voltage-dependent channels in the E(2)
      induced [Ca(2+)](i) increase was confirmed by the specific L-type Ca(2+) channel
      inhibitor nifedipine. For comparison, the D9 mERalpha-depleted subline was
      insensitive to steroid action via this signaling mechanism. [Ca(2+)](i) elevation
      was correlated with prolactin (PRL) release in the F10 cell line in as little as
      3 min. E(2) caused a much higher PRL release than KCl treatment (which caused
      maximal Ca(2+) elevation), suggesting that secretion was also controlled by
      additional mechanisms. Participation of mERalpha in these effects was confirmed
      by the ability of E(2)-peroxidase (a cell-impermeable analog of E(2)) to cause
      these responses, blockage of the responses with the ER antagonist ICI 182 780,
      and the inability of the E(2) stereoisomer 17alpha-E(2) to elicit a response.
      Thus rapid exocytosis of PRL is regulated in these cells by mERalpha signaling to
      specific Ca(2+) channels utilizing extracellular Ca(2+) sources and additional
      signaling mechanisms.

PMID- 15494611
TI  - Stearoyl-CoA desaturase 1 deficiency increases insulin signaling and glycogen
      accumulation in brown adipose tissue.
AB  - Stearoyl-CoA desaturase (SCD) catalyzes the synthesis of oleate (C18:1) and
      palmitoleate (C16:1), which are the main monounsaturated fatty acids of membrane
      phospholipids, triglycerides, wax esters, and cholesterol esters. Previously, we
      showed that SCD1 deficiency elevates insulin-signaling components and
      downregulates protein-tyrosine phosphatase-1B (PTP-1B) in muscle, a major insulin
      sensitive tissue. Here we found that, in brown adipose tissue (BAT), another
      insulin-sensitive tissue, the basal tyrosine phosphorylations of insulin receptor
      (IR) and IR substrates (IRS-1 and IRS-2) were upregulated in SCD1(-/-) mice
      compared with wild-type mice. The association of IRS-1 and IRS-2 with the alpha
      p85 subunit of phosphatidylinositol 3-kinase as well as Akt-Ser(473) and Akt
      Thr(308) phosphorylation is also elevated in the SCD1(-/-) mice. The mRNA
      expression, protein levels, and activity of PTP-1B implicated in the attenuation
      of the insulin signal are reduced in the SCD1(-/-) mice. The content of GLUT4 in
      the plasma membrane increased 2.5-fold, and this was accompanied by a 6-fold
      increase in glucose uptake in BAT of SCD1(-/-) mice. The increased glucose uptake
      was associated with higher glycogen synthase activity and glycogen accumulation.
      In the presence of insulin, [U-(14)C]glucose incorporation into glycogen was
      increased in BAT of SCD1(-/-) mice. Taken together, these studies illustrate
      increased insulin signaling and increased glycogen metabolism in BAT of SCD1(-/-)
      mice.

PMID- 15494612
TI  - Expression and activity of steroid aldoketoreductases 1C in omental adipose
      tissue are positive correlates of adiposity in women.
AB  - We examined expression and activity of steroid aldoketoreductase (AKR) 1C enzymes
      in adipose tissue in women. AKR1C1 (20alpha-hydroxysteroid dehydrogenase; 20alpha
      HSD), AKR1C2 (3alpha-HSD-3), and AKR1C3 (17beta-HSD-5) are involved mainly in
      conversion of progesterone to 20alpha-hydroxyprogesterone and inactivation of
      dihydrotestosterone to 5alpha-androstane-3alpha,17beta-diol. Abdominal
      subcutaneous and omental adipose tissue biopsies were obtained during abdominal
      hysterectomies in seven women with low visceral adipose tissue (VAT) area and
      seven age- and total body fat mass-matched women with visceral obesity. Women
      with elevated VAT areas were characterized by significantly higher omental
      adipose tissue 20alpha-HSD and 3alpha-HSD-3 mRNA abundance compared with women
      with low VAT accumulations (1.4- and 1.6-fold differences, respectively; P <
      0.05). Omental and subcutaneous adipose tissue 3alpha-HSD activities were
      significantly higher in women with high vs. low VAT areas (P < 0.05 for both
      comparisons). Total and visceral adiposities were positively associated with
      omental 20alpha-HSD mRNA level (r = 0.75, P < 0.003 for fat mass; r = 0.57, P <
      0.04 for VAT area) and omental 3alpha-HSD-3 mRNA level (r = 0.68, P < 0.01 for
      fat mass; r = 0.74, P < 0.003 for VAT area). Enzyme activities in both depots
      were also positively correlated with adiposity measures. Omental adipose tissue
      enzyme expression and activity were positively associated with omental adipocyte
      size and LPL activity. In conclusion, mRNA abundance and activity of AKR1C
      enzymes in abdominal adipose tissue compartments are positive correlates of
      adiposity in women. Increased progesterone and/or dihydrotestosterone reduction
      in abdominal adipose tissue may impact locally on fat cell metabolism.

PMID- 15494613
TI  - Creatine feeding increases GLUT4 expression in rat skeletal muscle.
AB  - The purpose of this study was to investigate the potential role of creatine in
      GLUT4 gene expression in rat skeletal muscle. Female Wistar rats were fed normal
      rat chow (controls) or chow containing 2% creatine monohydrate ad libitum for 3
      wk. GLUT4 protein levels of creatine-fed rats were significantly increased in
      extensor digitorum longus (EDL), triceps, and epitrochlearis muscles compared
      with muscles from controls (P < 0.05), and triceps GLUT4 mRNA levels were
      approximately 100% greater in triceps muscles from creatine-fed rats than in
      muscles from controls (P < 0.05). In epitrochlearis muscles from creatine-fed
      animals, glycogen content was approximately 40% greater (P < 0.05), and insulin
      stimulated glucose transport rates were higher (P < 0.05) than in epitrochlearis
      muscles from controls. Despite no changes in [ATP], [creatine],
      [phosphocreatine], or [AMP], creatine feeding increased AMP-activated protein
      kinase (AMPK) phosphorylation by 50% in rat EDL muscle (P < 0.05). Creatinine
      content of EDL muscle was almost twofold higher for creatine-fed animals than for
      controls (P < 0.05). Creatine feeding increased protein levels of myocyte
      enhancer factor 2 (MEF2) isoforms MEF2A ( approximately 70%, P < 0.05), MEF2C (
      approximately 60%, P < 0.05), and MEF2D ( approximately 90%, P < 0.05), which are
      transcription factors that regulate GLUT4 expression, in creatine-fed rat EDL
      muscle nuclear extracts. Electrophoretic mobility shift assay showed that DNA
      binding activity of MEF2 was increased by approximately 40% (P < 0.05) in
      creatine-fed rat EDL compared with controls. Our data suggest that creatine
      feeding enhances the nuclear content and DNA binding activity of MEF2 isoforms,
      which is concomitant with an increase in GLUT4 gene expression.

PMID- 15494615
TI  - Impaired physical performance and the assessment of dementia of the Alzheimer
      type.
AB  - CONTEXT: Impaired physical performance may confound the clinical assessment of
      dementia of the Alzheimer type (DAT). OBJECTIVES: Determine whether: (1) Physical
      Performance Test (PPT) scores are associated with the Clinical Dementia Rating
      (CDR), (2) PPT scores are correlated with clinical measures of health, and (3)
      impaired physical performance affects the clinical assessment of DAT. DESIGN: A
      retrospective and cross-sectional study. SETTING: An Alzheimer's Disease Research
      Center. PARTICIPANTS: Ninety-nine research volunteers aged 85 years and older
      were assessed from September 1997 through July 1999; 45 had DAT (CDR = 0.5-2),
      and 54 were nondemented controls. MEASUREMENTS: Clinical health history, daily
      functioning, physical and neurologic status, CDR, sum of boxes, and total PPT
      score were obtained during clinical evaluation. Independently assessed
      psychometric measures of verbal and nonverbal episodic and semantic memory,
      visuospatial abilities, and psychometric speed yielded to a factor score
      representing general cognitive function. Our outcome measure was the CDR (ie, the
      clinical dementia rating, where higher scores indicate greater dementia
      severity). RESULTS: The majority (88%) of subjects in this sample of demented and
      nondemented older adults had some degree of physical impairment as measured by
      the PPT. Correlational analyses identified clinically important relationships
      (/taub/ > 0.30, p < 0.05) between impaired PPT performance, higher CDR rating,
      and poor general health, including difficulty ambulating. The correlation between
      PPT performance and dementia severity (taub = -0.36) decreased after controlling
      for cognitive ability (taub = -0.19). The correlation between the cognitive
      factor score and dementia severity when PPT performance was controlled (taub = 
      0.60) was similar to the unadjusted correlation of the factor score with dementia
      severity (taub = -0.64). CONCLUSIONS: The presence of some degree of physical
      impairment was common in our sample, and PPT scores correlated with both physical
      and cognitive impairment. Nevertheless, Alzheimer Disease Research Center
      clinicians appear able to successfully distinguish between physical and cognitive
      causes of functional impairment and assign a CDR rating that accurately reflects
      DAT severity in individuals with impaired physical performance.

PMID- 15494616
TI  - Category fluency in mild cognitive impairment: reduced effect of practice in test
      retest conditions.
AB  - Verbal fluency tests are commonly used in neurocognitive and mental status
      examinations in patients with suspected dementia. Inflation of test scores as a
      result of practice effects may yield false-negative results in test-retest and
      multidisciplinary settings, particularly among patients with mild cognitive
      deficits. To address this issue, animal naming was administered twice within a 1
      week period to a group of individuals referred for suspected dementia who were
      ultimately diagnosed with mild cognitive impairment (MCI; amnestic form),
      probable Alzheimer disease (AD), or no dementia. A 2 x 3 repeated-measures
      analysis of variance revealed a statistically significant interaction between
      administration time and group. Post hoc analyses indicated that nondemented
      controls were the only group to demonstrate a significant practice effect,
      producing an average of approximately three more animal names at time two. Like
      patients with a diagnosis of AD, subjects with amnestic MCI failed to benefit
      from repeated exposure to the animal naming test, and only controls showed an
      average improvement upon retest. This underscores the cognitive similarity
      between individuals diagnosed with amnestic MCI and AD and suggests that
      improvement upon retest may be a diagnostically useful finding.

PMID- 15494617
TI  - Disease stage in Alzheimer disease and treatment effects of rivastigmine.
AB  - The efficacy and tolerability of the cholinesterase inhibitor rivastigmine in the
      treatment of Alzheimer disease (AD) have been demonstrated in several clinical
      trials, which included patients with a wide range of dementia severities. To
      investigate the association between severity of disease and treatment response,
      the combined data from three large randomized, placebo-controlled trials were
      analyzed. The pooled patient population was stratified into three cohorts showing
      moderately severe (Mini-Mental State Examination score [MMSE] < or = 15),
      moderate (MMSE 16-22), and mild (MMSE > or = 22) dementia. In each cohort, the
      effects of rivastigmine 6 to 12 mg/day versus placebo were evaluated using the
      cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-cog) and the
      Progressive Deterioration Scale. Rivastigmine 6 to 12 mg/day maintained ADAS-cog
      scores at or above placebo levels in all cohorts, while cognitive deterioration
      with placebo was progressive and severity dependent. Activities of daily living
      showed statistically significant benefits with rivastigmine across all severity
      cohorts.

PMID- 15494618
TI  - Association of hyperhomocysteinemia in Alzheimer disease with elevated neopterin
      levels.
AB  - In patients with dementias including Alzheimer disease (AD), elevated blood
      concentrations of homocysteine are common, often going along with low normal
      folate and vitamin B12. Immune activation leading to oxidative stress also seems
      to play an important role in the pathogenesis of AD. To find out a possible
      relationship between immune activation and the development of moderate
      hyperhomocysteinemia, we determined serum concentrations of homocysteine, folate,
      vitamin B12 and immune activation markers 75 kD soluble TNF receptor (sTNF-R75)
      and neopterin in 38 patients with clinically diagnosed AD. A subgroup of patients
      (45%) presented with increased homocysteine concentrations in comparison to
      reference ranges in healthy controls of similar age. Also, concentrations of
      immune activation markers were elevated in a significant proportion of patients.
      In 17 patients with moderate hyperhomocysteinemia, concentrations of neopterin
      were higher than in those with lower homocysteine (p < 0.001). Homocysteine
      correlated with folate (rs= -0.43; p < 0.01) and neopterin (rs= 0.506; p <
      0.001). The data suggest that immune activation and concomitant production of
      reactive oxygen species in patients with AD could be involved in the development
      of hyperhomocysteinemia via an enhanced decomposition of folate.

PMID- 15494619
TI  - Pathways to dementia diagnosis: evidence for cross-ethnic differences.
AB  - The diagnosis of dementia often occurs well after the onset of the disease.
      Studies of help-seeking behavior may help illuminate why delays occur. SPECIFIC
      AIMS: (1) To describe pathways to diagnosis from the perspective of family
      caregivers and (2) to compare help-seeking patterns and experiences across three
      ethnic groups. METHODS: Semi-structured qualitative interviews were conducted
      with 39 ethnically diverse family dementia caregivers. Interviews were coded for
      help-seeking events (initial help-seeking, referrals to secondary helpers, and
      site of final diagnosis), pathway types, and adverse experiences within the
      healthcare system along pathways to diagnosis. RESULTS: Help-seeking was most
      often initiated by family members or formal care providers (ie, healthcare
      providers or social workers), usually in outpatient primary care settings but
      also elsewhere (eg, social service agencies, hospitals). "Secondary" formal
      helpers were often involved, usually through self-referral by families rather
      than by healthcare providers. While most families reported receiving a "final"
      diagnosis, a small minority of predominantly Chinese-American families did not.
      Four distinct pathways to diagnosis were identified and found to vary
      significantly (p < 0.03) across the three ethnic groups, which we label as smooth
      pathways, crisis events pathways, fragmented pathways, and dead-end pathways.
      Adverse experiences in the healthcare system were common and included
      unsatisfactory diagnosis disclosure and explanation, inadequate workup, uncaring
      or insensitive attitude, language barriers, and discrimination. CONCLUSIONS:
      Cross-ethnic differences were found in both pathway types and in adverse
      experiences.

PMID- 15494620
TI  - Comparison of clinic-based home assessment to a home visit in demented elderly
      patients.
AB  - Home visits assessing demented elderly patients yield important information but
      are perceived to be expensive. We investigated the utility of a home assessment
      during a clinic visit. A total of 200 demented subjects attending an outpatient
      geriatric assessment program were enrolled in a prospective, repeated-measures
      design study comparing the yield of a structured clinic-based home assessment
      with the yield of a home visit (the criterion standard). A total of 172 subjects
      completed the protocol. The average age was 76 +/- 7 years, 68% were female, 48%
      married, and the average Mini-Mental Status Examination score was 21 +/- 7
      points. Only 3 subjects had complete agreement by site, 162 subjects had at least
      one problem identified only at the home visit, and 7 subjects had at least one
      problem identified only at the clinic. There were 376 problems identified at both
      sites, 422 identified only by the home visit, and 478 identified only in the
      clinic. Problems related to patient safety and caregiver issues were the two most
      common general categories. Eighty-four percent of the problems identified only at
      the home visit were potentially serious and 24% of problems identified at both
      sites were rated as more serious at the home visit. A clinic-based home
      assessment is not comparable to a home visit for assessing the home environment
      of demented elderly patients.

PMID- 15494621
TI  - Forgoing artificial nutrition and hydration in nursing home patients with
      dementia: patients, decision making, and participants.
AB  - OBJECTIVE: The purpose of this study is to investigate the characteristics of
      patients for whom it is decided to forgo artificial nutrition and hydration (ANH)
      and characteristics of the ANH decision-making process. We conducted an
      observational study with the use of written questionnaires. For 178 nursing home
      patients with dementia, the treating nursing home physician (NHP), a family
      member, and a nurse filled out a questionnaire directly after the decision was
      made to forgo ANH. RESULTS: We found that most patients had severe dementia and
      two thirds had an acute illness. Advance care planning had taken place in 68% of
      the cases. In two thirds of the cases, the primary aim in forgoing ANH was to
      avoid unnecessary prolongation of life; and nurses seemed to have less influence
      on the decision-making process than NHPs and family members. Almost all
      respondents evaluated the decision-making process as "good" or "adequate."
      Dissatisfaction was felt when the decision had to be made under the pressure of
      time constraint. CONCLUSIONS: On the basis of these results, we recommend that
      discussions that include NHPs, family members, and nurses concerning decisions
      about possible future situations be held on a regular basis. This will form the
      basis for the difficult ANH decision and will probably reduce the pressure of
      time constraint.

PMID- 15494622
TI  - Diagnostic utility of neuropsychological performance and quantitative MRI-based
      measurement in Alzheimer disease.
AB  - This study was designed to examine the roles of the characteristic cognitive
      indicators and specific MRI-based measurements in the differential diagnoses of
      Alzheimer disease (AD), vascular dementia (VaD), and normal aging. Fifty-two
      probable AD patients were recruited for the study. Twenty-seven VaD patients and
      35 age-matched normal older adults (NC) were included as controls. All subjects
      underwent a battery of standardized neuropsychological tests. The MRI-based
      quantification technique was used to measure the volumes and T2 relaxation time
      (T2) of medial temporal lobe structures. Stepwise discriminant analyses showed
      cognitive indicators had a sensitivity ranging from 82% to 100% and specificity
      from 82% to 97% for differentiating AD from non-AD cases (VaD and normal
      controls), and the quantitative MRI-based measurements of medial temporal lobe
      structures correctly classified AD cases from non-AD cases with sensitivity from
      80% to 96% and specificity from 83% to 97%. ROC curve analyses showed that the
      combination of cognitive and MRI measurements slightly increased the diagnostic
      accuracy of AD. The results suggest that both cognitive indicators and MRI-based
      medial temporal lobe measurements may be useful in differentiating AD from VaD
      and normal older adults. The combination of these possible indicators is
      promising in the early diagnosis of AD.

PMID- 15494623
TI  - Research consent for cognitively impaired adults: recommendations for
      institutional review boards and investigators.
AB  - Adults with cognitive impairment are considered a vulnerable population. The
      conditions associated with cognitive impairment, such as dementia and delirium,
      cause great suffering to affected patients and their families. Improving clinical
      care for these conditions depends on research involving cognitively impaired
      participants. Cognitive impairment is at times associated with partial or full
      impairment of the capacity to consent to research. This both limits the ability
      of the individual to consent personally to research participation, and also
      increases pressure upon Institutional Review Boards (IRBs) and investigators to
      place additional safeguards for the appropriate participation of cognitively
      impaired individuals in research. While the ethical and legal principles
      permitting and safeguarding the participation of cognitively impaired persons in
      research are generally agreed upon, there are no specific methods that
      operationalize these principles in a language that can be used by IRBs and
      researchers to guide their day-to-day work in this area. This document contains
      recommendations that IRBs and investigators can use to operationalize the
      informed consent process for individuals with cognitive impairment. In situations
      in which IRBs might not have specific policies in this area, this guideline may
      also serve as the foundation for such policies. The recommendations discuss when
      to consider that cognitively impaired participants might be involved in a
      research project, the use of screening for cognitive impairment, the conduct of
      assessments evaluating capacity to consent to research, situations in which
      proxies might consent for research participation in the place of cognitively
      impaired participants, how to go about identifying appropriate proxies, and how
      to deal with the loss of consent capacity in the course of a research project.

PMID- 15494625
TI  - Depression as an emotional response in Alzheimer disease.

PMID- 15494629
TI  - Nurses educated in other countries: coming to America.

PMID- 15494630
TI  - Quality assurance requirements for contract/agency nurses.
AB  - According to the American Hospital Association, over half of its member hospitals
      used contract/agency nurses to fill vacant positions in 2000. It is imperative
      that companies that provide nurses be able to furnish, to employing hospitals,
      documentation that demonstrates each nurse's ability to practice safely and
      legally. The article specifies the areas where documentation is needed along with
      discussion of each area. The nurse executive needs to be aware of these issues to
      ensure that the facility in which he or she works is getting the appropriate
      information regarding supplemental staff in order to protect against licensure
      and litigation repercussions.

PMID- 15494633
TI  - Transitions from student to practicing nurse.

PMID- 15494634
TI  - Peripheral benzodiazepine receptor and its clinical targeting.
AB  - Tumor cell targeted therapies, by induction or enhancement of apoptosis,
      constitute recent promising approaches achieving more specific anti-tumor
      efficacy. The peripheral benzodiazepine receptor (PBR), which belongs to the
      permeability transition pore (PTP), the central regulatory complex of apoptosis,
      is a potential target. A number of findings argue in favor of the development of
      PBR targeting approaches: (i) overexpression of PBR has been described in a large
      range of human cancers, (ii) PTP-mediated regulation of programmed cell death is
      an apoptotic-inducing factor-independent check-point that could be modulated by
      various conventional cancer therapies, and (iii) PBR ligation enhances apoptosis
      induction in many types of tumors and reverses Bcl-2 cytoprotective effects.
      Altogether, these observations support the use of PBR-directed drugs,
      particularly PBR ligands such as Ro5-4864, in the treatment of human cancers.

PMID- 15494635
TI  - Biweekly administration of 24-h infusion of irinotecan followed by a 1-h infusion
      of docetaxel: a phase I study.
AB  - We developed a chemotherapy combination regimen based on preclinical data
      suggesting synchronization of cancer cells in G2/M phase when exposed to
      irinotecan over a protracted period. This phase I study aimed to determine the
      toxicity spectrum, and define the dose-limiting toxicity (DLT), maximum tolerated
      dose (MTD) and recommended optimal dose (ROD) of irinotecan infused over 24 h and
      followed by a 1-h infusion of 30 mg/m2 docetaxel. Starting dose for irinotecan
      was 30 mg/m2 and escalation proceeded at 30 mg/m2 increments, in cohorts of three
      to six patients until the MTD was reached. A dose between the MTD and the
      previous level was explored to further define the ROD. Thirty-two patients with
      advanced refractory cancers (median age 64, 19 male) received 190 treatment
      courses at five dosing levels of irinotecan: 30 mg/m2 (n=6 patients), 60 (n=3),
      90 (n=7), 120 (n=8) and 105 (n=8). The MTD and ROD was 120/30 and 105/30 mg/m2.
      DLTs were diarrhea and neutropenia. Antitumor activity was modest. The ROD of
      biweekly administration of 24-h irinotecan followed by 1-h docetaxel is 105 and
      30 mg/m2, respectively. The low hematological toxicity and modest activity
      observed leave questions concerning the optimal timing of this combination.

PMID- 15494636
TI  - Acute effects of tamoxifen and third-generation aromatase inhibitors on
      menopausal symptoms of breast cancer patients.
AB  - Endocrine treatments of breast cancer patients antagonize estrogen and may lead
      to consequences of estrogen deprivation including menopausal symptoms. We
      analyzed the changes in frequency and severity of menopausal symptoms in patients
      receiving tamoxifen or aromatase inhibitors and identified factors influencing
      these symptoms. One hundred and eighty-one consecutive postmenopausal breast
      cancer patients scheduled to start endocrine treatment were included in this
      prospective study. A menopause symptom questionnaire covering vasomotor,
      atrophic, psychological, cognitive and somatic symptoms was filled in at
      baseline, and after 1 and 3 months of therapy. Both first-line tamoxifen and
      aromatase inhibitors induced an increase in the occurrence and severity of hot
      flashes (p<0.0001 and p=0.014, respectively). Musculoskeletal pain and
      dyspareunia significantly increased under first-line non-steroidal aromatase
      inhibitors (p=0.0039 and p=0.001, respectively), while patients under tamoxifen
      had significant decrease in sexual interest (p< or =0.0001). Younger age was
      associated with more hot flashes and vaginal dryness at baseline, and after 1 and
      3 months of therapy (all p<0.02). We conclude that there are significant
      differences between the early effects of tamoxifen and aromatase inhibitors on
      menopausal symptoms of breast cancer patients. Our results underscore the need
      for safe and effective non-hormonal interventions to alleviate vasomotor and
      musculoskeletal symptoms which were the most prevalent and severe symptoms.

PMID- 15494637
TI  - Chemoradiation with gemcitabine for cervical cancer in patients with renal
      failure.
AB  - The prognosis of cervical cancer patients with renal failure secondary to
      obstructive uropathy is poor. Our objective was to analyze our experience in the
      management with chemoradiation of untreated cervical cancer patients complicated
      by obstructive nephropathy and kidney dysfunction. Untreated patients with
      cervical cancer and renal failure as manifested by raised serum creatinine were
      treated with pelvic radiotherapy concurrently with weekly gemcitabine at 300
      mg/m2. Response, toxicity and renal function pre- and post-therapy were
      evaluated. Eight FIGO stage IIIB and one IVB patients were treated. Pre-treatment
      serum creatinine ranged from 1.6 to 18.5 mg/100 ml (median 3.3, mean 6.8) and
      creatinine clearance varied from 4 to 57 mg/ml/min (median 17, mean 22.1). Four
      patients had a percutaneous nephrostomy placed and four patients had symptoms
      from kidney failure. All patient completed chemoradiation. Most patients had
      grade 3 leukopenia and neutropenia. Dermatitis, colitis and proctitis were
      common. All patients had improvement in creatinine clearance (pre-therapy 22.78,
      post-therapy 54.3 mg/ml/min) (p=0.0058) and all but one normalized serum
      creatinine. Eight (89%) of nine patients achieved complete response and one
      patient had persistence. At a median follow-up of 11 months (range 6-14), all
      patients are alive, one with pelvic and another with systemic disease. Ureteral
      obstruction causing any degree of renal insufficiency should not be a
      contraindication to receive chemoradiation to attempt cure. In this setting where
      cisplatin-based therapy is contraindicated, the use of gemcitabine may be
      considered.

PMID- 15494638
TI  - Peripheral neuropathy associated with capecitabine.
AB  - 5-fluorouracil (5-FU)-associated peripheral neuropathy is an uncommon event.
      Capecitabine (CAP) is a pro-drug of 5-FU and peripheral neuropathy associated
      with CAP has not been reported. During analysis of 28 patients receiving CAP with
      concomitant radiation (XRT) for pancreatic cancer (resected or locally advanced),
      two patients developed signs and symptoms consistent with peripheral neuropathy.
      Patients received CAP 1200-1600 mg/m2 in two divided doses with XRT (total 5040
      5400 Gy) x 6 weeks, followed by 4 weeks rest, then 6 cycles of CAP 2000-2500
      mg/m2 in two divided doses x 14 days every (q) 3 weeks. Patients were assessed
      weekly during CAP-XRT and q 3 weeks during CAP alone. Patient A reported right
      leg weakness (foot drop) during week 4 of CAP-XRT (1600 mg/m2). Patient B
      developed perioral and upper extremity paresthesias during the fourth cycle of
      CAP alone (2500 mg/m2). Dihydropyrimidine dehydrogenase (DPD) activity was
      measured by radioisotopic assay using lysates of peripheral blood mononuclear
      cells. Neurologic examination revealed right foot drop in Patient A and was
      unremarkable in Patient B. Central nervous system imaging was negative.
      Electromyogram and nerve conduction studies showed sensorimotor peripheral
      neuropathy in both patients. DPD activity was normal in both patients. There was
      no evidence of disease progression. Neurologic symptoms resolved after stopping
      CAP for 4 weeks in Patient A, with no recurrence after reinitiating CAP alone at
      2000 mg/m2. Patient B continued at 80% of standard dose (2000 mg/m2) and symptoms
      resolved without further intervention. We conclude peripheral neuropathy with 5
      FU is rare. Neurotoxicity occurs most often with intermittent high dose 5-FU as
      bolus injection or 24- to 48-h infusions. The etiology of neurotoxicity in our
      two patients remains unclear; however, as CAP is rapidly metabolized to 5-FU in
      patients with normal liver function, it is likely that 5-FU or its active
      metabolites (fluoro-beta-alanine) were contributing factors. Knowledge regarding
      potential adverse effects of CAP is paramount and dose modification is indicated
      with development of neurotoxicity.

PMID- 15494639
TI  - Enhanced therapeutic efficacy of a novel liposome-based formulation of SN-38
      against human tumor models in SCID mice.
AB  - SN-38 is an active metabolite of CPT-11. The poor solubility of SN-38 in any
      pharmaceutically acceptable solvent and pH-dependent activity has limited its
      clinical use. Our objective was to evaluate an easy-to-use liposome-based
      formulation of SN-38 (LE-SN38) and compare the antitumor activity with its pro
      drug CPT-11 against cancer cell lines and human xenograft tumor models. The
      cytotoxicity of LE-SN38 and CPT-11 was determined in four human cancer cell lines
      using the sulforhodamine B assay. The therapeutic efficacy was tested against
      human colon (HT-29) and breast (MX-1) xenograft tumor models in SCID mice. LE
      SN38 with greater than 95% drug entrapment was found to be highly cytotoxic
      against four different cell lines with GI50 values of less than 0.1 microM. In
      the HT-29 tumor model, LE-SN38 (q x d5) at 2, 4 or 8 mg/kg resulted in 33, 81 and
      91% tumor growth inhibition, respectively, compared to the drug-free liposome
      group. In contrast, similar dose levels of CPT-11 treatment led to only 2, 36 and
      46% growth inhibition. For the MX-1 model, LE-SN38 (q x d5) regressed tumor
      growth by 44 and 88% at 4 and 8 mg/kg dose, respectively, whereas no regression
      was observed in the CPT-11-treated group. We conclude that LE-SN38 is a novel
      liposome-based formulation with enhanced therapeutic efficacy against human tumor
      models.

PMID- 15494640
TI  - Characterization of molecular events in a series of bladder urothelial carcinoma
      cell lines with progressive resistance to arsenic trioxide.
AB  - Our previous studies have shown that arsenic trioxide (As2O3), a novel anti
      cancer agent, may be active against urothelial carcinomas. A series of bladder
      urothelial carcinoma cells with progressive As2O3 resistance were established and
      studied to reveal molecular events in relation to the mechanisms of resistance to
      As2O3. A sensitive parental line (NTUB1) and three As2O3-resistant sublines
      (NTUB1/As) were used with their IC50s being 0.9, 1.2, 2.5 and 4.9 microM,
      respectively. Cellular resistance to As2O3 was associated with a lowered
      proliferation profile (increased p53 and p21Waf1/Cip1 and decreased c-Myc levels)
      and a greater resistance to apoptosis (elevated Bcl-2 levels). Cells with a
      stronger resistance had higher expressions of superoxide dismutase (Cu/Zn) and
      hMSH2 (but not hMLH1). GSH contents were up-regulated in resistant cells in a
      dose-dependent manner. The DNA-binding activities of NF-kappaB and AP-1 were down
      regulated in resistant cells in a dose-dependent manner. Profound molecular
      alterations occur during the acquisition of secondary As2O3 resistance. Our in
      vitro cellular model may help to reveal resistance mechanisms to As2O3 in bladder
      urothelial carcinoma cells.

PMID- 15494641
TI  - Tamoxifen long-term treatment in vitro alters the apoptotic response of MCF-7
      breast cancer cells.
AB  - In this study, we examined alterations in the apoptotic response of tamoxifen
      (TAM)-resistant breast cancer cells. We used an in vitro selection approach for
      TAM resistance by means of long-term culture of MCF-7 breast cancer cells with
      increasing concentrations of TAM. The apoptotic response to TAM was determined by
      means of ELISA measurement of apoptotic DNA-histone complexes in cytoplasm and by
      Annexin-V staining. MCF-7(LT) cells isolated after 5 months of long-term
      treatment with TAM exhibited a significantly reduced apoptotic response to this
      drug, even if administered in high concentrations up to 20 microM. This reduced
      apoptotic response was also observed after treatment with the topoisomerase II
      inhibitor etoposide, a pro-apoptotic antineoplastic drug. Microarray experiments
      comparing the transcriptome of MCF-7(LT) and wild-type cells revealed both the
      down-regulated expression of several genes coding for pro-apoptotic proteins and
      the up-regulation of genes coding for apoptosis inhibitors. Further experiments
      to determine expression changes of the receptor tyrosine kinases HER2 and
      epidermal growth factor receptor did not reveal any alterations in MCF-7(LT) if
      compared to wild-type cells. Our findings suggest that long-term treatment with
      TAM in vitro does not necessarily change the expression of receptor tyrosine
      kinases, but can modulate the expression of apoptotic key genes impairing the
      apoptotic response of MCF-7 breast cancer cells.

PMID- 15494642
TI  - In vitro toxicity of bisphosphonates on human neuroblastoma cell lines.
AB  - Neuroblastoma is the commonest extracranial solid tumor of childhood and
      frequently metastasizes to the bone. Bisphosphonates are standard treatment of
      osteolytic lesions by bone metastasis. Since recent studies suggested direct
      antitumor effects of bisphosphonates, we screened the toxicity of different
      bisphosphonates on neuroblastoma cell lines. The nitrogen-containing
      bisphosphonate pamidronate was significantly more toxic on a panel of eight
      neuroblastoma cell lines than the non-nitrogen-containing bisphosphonates,
      clodronate and tiludronate. After 72 h, GI50 concentrations (inhibiting cell
      growth by 50% compared to untreated controls) for pamidronate ranged from 12.8 to
      >500 microM. CHLA-90 and SH-SY5Y were the most sensitive cell lines. In CHLA-90,
      zoledronate was the most cytotoxic bisphosphonate, followed by alendronate,
      pamidronate and ibandronate. In SH-SY5Y, alendronate was the most cytotoxic
      bisphosphonate, followed by ibandronate, pamidronate and zoledronate. The GI50
      values after 72 h were 34.1 (SH-SY5Y) and 3.97 microM (CHLA-90) for zoledronate,
      and 22.4 (SH-SY5Y) and 9.55 microM (CHLA-90) for alendronate. Neuroblastoma cells
      treated with bisphosphonates showed signs of differentiation and finally
      underwent apoptosis. The observed GI50 concentrations suggest that local nitrogen
      containing bisphosphonate concentrations at the bone interface can directly
      target neuroblastoma cell penetration into the bone matrix. In summary, these
      observations warrant the investigation of adjuvant bisphosphonate treatment in
      controlled clinical trials.

PMID- 15494643
TI  - Non-toxic and short treatment with gemcitabine inhibits in vitro migration of HT
      1080 cells.
AB  - Gemcitabine has demonstrated clinical activity in solid tumors. Several in vitro
      studies were carried out regarding its metabolism, toxicity and cell cycle
      effects, but none was done on the anti-metastasis potential of the drug. We
      sought to determine the effect of gemcitabine concentrations on migration
      velocity of HT-1080 cells at concentrations which do not alter cell cycle
      progression and proliferation. Cells were treated for 1 or 5 h at IC10-70 of
      gemcitabine in order to estimate its effects on viability, proliferation and
      migration capacity using flow cytometry and microscopy imaging, respectively. The
      gemcitabine treatment for 1 h had no effect on cell proliferation, viability,
      cycle or migration on HT-1080 cells. Even though the 5 h of exposure at IC10,
      IC20 and IC50 concentrations did not affect cell viability, proliferation and
      cell cycle repartition, the mean velocity of HT-1080 dramatically decreased by 50
      and 30%, respectively. Gemcitabine at IC70 concentrations for 5 h of exposure
      first induced a time course inhibition of proliferation, together with a decrease
      in viability and altered cell morphology, and then inhibited cell migration by
      50%. These data suggest the possibility to couple the anti-migratory property of
      gemcitabine with the known anti-tumoral effect in the treatment of tumors with
      high metastatic potential.

PMID- 15494648
TI  - Developing data for practice and management: an Australian educational
      initiative.
AB  - As in other countries, the Australian healthcare industry is replete with massive
      data collections, often not used effectively to generate meaningful information
      to inform decision making, particularly at the operational or clinical level.
      While senior administrators and planners may use the data for forecasting or
      benchmarking, it is imperative that clinicians, including nurses and nurse
      managers, appreciate the value of the data and develop the knowledge and skills
      to access, analyze, and use it to inform their decision making. Only in the last
      decade or so have increasing numbers of nurses moved toward higher levels of
      information technology competence, particularly as information technology
      applications entered the healthcare sector. Facility in understanding standard
      administrative data is an important new skill for nurses who have an interest in
      information management. It is a skill that can readily be taught and its value
      becomes clearly evident to the students. This article describes an Australian
      University's Faculty of Nursing's approach to teaching this material at the
      master's level.

PMID- 15494644
TI  - Synergistic interaction between gefitinib (Iressa, ZD1839) and paclitaxel against
      human gastric carcinoma cells.
AB  - We have evaluated the antitumor effects of gefitinib (Iressa, ZD1839) in SNU-1
      human gastric cancer cells (hMLH1-deficient and epidermal growth factor receptor
      overexpressed) when given alone or as a doublet with oxaliplatin (LOHP), 5
      fluorouracil (5-FU) or paclitaxel (PTX). The four drugs showed IC50s ranging from
      1.81 nM to 13.2 microM. LOHP and PTX induced G2/M arrest, 5-FU increased S phase,
      and gefitinib increased G1 in a concentration-dependent manner. The analysis
      using the previously developed cytostatic TPi model showed that 64 and 80% of the
      overall growth inhibition was attributed to cell cycle arrest in cells exposed to
      7.55 microM of LOHP or 10 nM of PTX for 72 h, respectively. PTX + gefitinib
      showed greatest synergism as determined by combination index analysis and
      apoptosis induced by PTX was potentiated by the co-administration of gefitinib.
      LOHP + gefitinib showed a similar, although to a lesser degree, synergistic
      effect. This study demonstrates the antitumor activity and the significant cell
      cycle arrest induced by gefitinib in SNU-1 human gastric carcinoma cells, and its
      synergistic interaction with LOHP and PTX.

PMID- 15494649
TI  - Strategic use of faculty workgroups to develop online interactive geriatric
      curricular modules.
AB  - Initiating a college-wide, complex multimedia approach to teaching-learning can
      be fraught with considerable challenges. The strategic use of faculty workgroups
      to maximize faculty involvement in the development and use of interactive Web
      based modules was one successful approach to overcoming such challenges. Use of
      faculty workgroups composed of grant team faculty members and course faculty
      during the development process recognized the faculty's curricular and content
      expertise and tapped individual creativity. Other successful approaches to
      meeting development challenges were the inclusion of a multimedia designer in
      faculty workgroups, demonstrations of technology at college council meetings and
      the use of familiar software by faculty to communicate module design ideas.
      Additional practical approaches for technology teams within higher education
      settings are presented from both person and design perspectives.

PMID- 15494651
TI  - Testing the reliability and validity of computer-mediated social support measures
      among older adults: a pilot study.
AB  - With the increasing number of older adult online users, the Internet and e-mail
      are becoming a new source of social support for older adults. To assess this
      computer-mediated social support, two traditional social support measures were
      modified: (1) the Lubben Social Network Scale and (2) the Medical Outcomes Study
      Social Support Survey. The purpose of this pilot study was to test the
      reliability and validity of these modified measures. This study was a single
      group descriptive study with two data collection points. Data were collected
      using Web surveys. A total of 38 older adult participants completed the first
      survey; 35, the second survey. The findings of this preliminary study provided
      evidence for the reliability, content validity, and, to a limited extent,
      construct validity, of the modified measures. Additional studies with a larger
      representative sample are needed to further examine the psychometric aspects of
      these measures.

PMID- 15494652
TI  - HESI exams: an overview of reliability and validity.
AB  - Schools of nursing are increasingly administering computerized exams developed by
      Health Education Systems, Inc (HESI) to evaluate student and program outcomes and
      provide evidence-based rationale for curriculum development and modification.
      This article describes the methods used to establish the reliability and validity
      of HESI specialty exams and HESI exit exams. Discussion of current reliability
      and validity findings and recommendations for future research to enhance the
      quantification of validity data for HESI exams are presented.

PMID- 15494653
TI  - NMAP: UK's nursing Internet gateway.
AB  - This article describes the development of NMAP, the UK academic gateway to high
      quality Internet resources for Nurses, Midwives and Allied health Professionals.
      The service is described and the rationale for NMAP summarized, focusing on the
      increasing use of Internet resources in nursing education and practice.
      International concerns over the quality of health information available on the
      Internet are considered, and the approach adopted by NMAP to quality filtering
      described. The usage data and results of evaluation studies show the need for
      this type of Internet gateway, and some of the lessons may be relevant to others
      involved in developing national high-quality Internet gateways for nurses.

PMID- 15494654
TI  - Predicting nurses' intention to quit with a support vector machine: a new
      approach to set up an early warning mechanism in human resource management.
AB  - This project developed a Support Vector Machine for predicting nurses' intention
      to quit, using working motivation, job satisfaction, and stress levels as
      predictors. This study was conducted in three hospitals located in southern
      Taiwan. The target population was all nurses (389 valid cases). For cross
      validation, we randomly split cases into four groups of approximately equal
      sizes, and performed four training runs. After the training, the average
      percentage of misclassification on the training data was 0.86, while that on the
      testing data was 10.8, resulting in predictions with 89.2% accuracy. This Support
      Vector Machine can predict nurses' intention to quit, without asking these nurses
      whether they have an intention to quit.

PMID- 15494656
TI  - [FRENCH: a new tool for clinical surgical research in France].

PMID- 15494657
TI  - [Management of malignant epithelial tumors of the ovary].
AB  - The notoriously poor prognosis of ovarian cancer requires optimal management by a
      multidisciplinary gynecologic and oncologic surgical team. Ovarian cancers which
      appear to be of early stage must be accurately staged to be sure that no
      potential metastatic sites are missed. Such an omission may have grave
      consequences for disease progression and may reduce the chances of cure in young
      patients. With advanced-stage ovarian carcinoma, the challenge is to perform a
      detailed pre-operative staging of the extent of disease to enable neo-adjuvant
      chemotherapy when the disease is judged to be inoperable and/or the the general
      condition of the patient is unsuitable for surgery. Only patients who have had
      complete cytoreductive surgery to all affected areas in the abdomen can hope to
      have an acceptable 5 year survival rate of 50%.

PMID- 15494658
TI  - [Preoperative bowel preparation--is it useful?].
AB  - Mechanical cleansing of the colon prior to elective colorectal surgery is a
      dogmatically established belief in surgery. Polyethylene glycol was extensively
      used in the 1980's and 1990's but has been largely replaced by other laxative
      solutions such as sodium phosphate which are better tolerated by the patient.
      Evidence-based data in the surgical literature question the dogma of routine
      mechanical bowel cleansing (8 randomized controlled studies and 4 meta-analyses).
      These data show with a good level of evidence that mechanical bowel preparation
      is unnecessary and perhaps harmful.

PMID- 15494659
TI  - [Incarceration of a calibrating band after vertical banded gastroplasty for
      morbid obesity: diagnostic and therapeutic implications].
AB  - About a case of migration of the strip of grading placed during a gastroplasty,
      and revealed by a severe complication on the occasion of the transformation of a
      typical Mason gastroplasty in Mac Lean gastroplasty, we formulate the following
      propositions: 1) The staple line dehiscence of Mason's vertical gastroplasty can
      be bound (connected) to an excessive tightening of the strip and let us suggest
      lengthening (stretching out) his 2 cm length with regard to the usually
      recommended dimension. 2) It is necessary to look for systematically this
      confinement, in case of reintervention for staple line dehiscence; to ignore it
      is to expose itself, if we transform the Mason surgery into Mac Lean surgery, to
      deteriorate a fistula which the staple line dehiscence had until then contributed
      to hide (darken).

PMID- 15494660
TI  - [Localization of parathyroid glands and strategy for resection for
      hyperparathyroidism].

PMID- 15494661
TI  - [Laparoscopic abdomino-perineal resection of the rectum].

PMID- 15494662
TI  - [Treatment of rectocele and internal rectal prolapse by transanal resection with
      stapled anastomosis].

PMID- 15494663
TI  - [Pancreatic metastasis from renal cancer].

PMID- 15494664
TI  - [Pseudohepatoma].

PMID- 15494665
TI  - [Intra-hepatic cholangiocarcinoma].
AB  - Intra-hepatic cholangiocarcinoma (IHCC) is a rare tumor which arises from the
      epithelial cells of the intra-hepatic bile ducts; it may develop in a healthy
      liver and bile ducts or in bile ducts with malignant predisposition (Caroli's
      syndrome, primary sclerosing cholangitis). It has the worst prognosis of any
      tumor arising in the liver. Unlike hepatocellular carcinoma, no predisposing
      factors or high-risk populations have been demonstrated for cholangiocarcinoma
      other than intraphepatic choledocholithiasis such as is seen in east Asian
      populations. The most common clinical sign is a palpable tumor mass emphasizing
      that the tumor is usually detected at an advanced stage. CT scanning yields much
      clinical information but ultrasound-guided needle biopsy is necessary for
      diagnosis. Aggressive surgical resection is the only treatment modality which has
      afforded even slight prolongation of survival; hepatic resection must be large
      with uninvolved resection margins. When an IHCC is deemed resectable (localized
      tumor without hepatic metastases or intrahepatic or extrahepatic lymph node
      spread), pre-operative tumor embolization may be useful; when jaundice is
      present, percutaneous drainage of the dilated biliary system of the liver to be
      spared may also be necessary. Neither adjuvant nor neo-adjuvant chemotherapy or
      radiotherapy have shown proof of efficacity. Cholangiocarcinoma complicates
      sclerosing cholangitis in 10-15% of cases and is very difficult to diagnose. IHCC
      may also develop in Caroli's syndrome, where it is commonly found incidentally on
      pathologic examination of a resection specimen after surgery for a complication
      of the disease.

PMID- 15494666
TI  - [40th congress of the American Society of Clinical Oncology--New Orleans, June 5
      8, 2004].

PMID- 15494667
TI  - [CT diagnosis of a trans-mesocolic internal hernia].

PMID- 15494668
TI  - [Malignant degeneration within an ileal loop following cystectomy].

PMID- 15494669
TI  - A comprehensive review of anti-reflux procedures completed by computer-assisted
      tele-surgery.
AB  - Gastro-esophageal reflux disease (GERD) is the most common esophageal disorder.
      Although GERD is an illness primarily treated by medical management, patients
      refractory to, or those unwilling to endure long-term medical therapy often
      undergo anti-reflux surgery. Laparoscopic surgery made the surgeon's task
      technically more challenging. While laparoscopy provides a good field of vision,
      all depth perception is lost. Furthermore, the movements of the chopstick-like
      instruments are counter-intuitive with limited degrees of freedom, diminished
      tactile feedback, and disassociated movement. Now that advanced minimally
      invasive surgeons have acquired the necessary skills to overcome these hurdles,
      technology has developed a way to make laparoscopic surgery easier. The latest
      advance in laparoscopic surgery is computer-assisted telesurgery (CATS) which
      allows the surgeon to be seamlessly submerged into the surgical field while being
      seated at a distance from the patient. The technological advances afforded by
      CATS make minimally-invasive surgery easier by adding stereoscopic vision, which
      provides depth perception, and the endo-wrist, which provides wrist-like
      dexterity within the abdominal cavity. The advantages of CATS are: the ergonomic
      positioning of the surgeon thus decreasing fatigue; stereoscopic vision with
      possibility of 10x magnification; wrist-like manual dexterity with intuitive
      motion; motion-scaling and tremor elimination all of which enhance precision and
      accuracy. A small yet growing body of evidence has provided information which
      suggests that the use of CATS for anti-reflux surgery is equivalent to the
      current gold standard, unassisted laparoscopy.

PMID- 15494670
TI  - Endoscopic therapy for gastroesophageal reflux disease: can it replace antireflux
      surgery?
AB  - This article addresses emergent endoluminal technologies currently available for
      the treatment of gastroesophageal reflux disease (GERD) and compares it to the
      laparoscopic Nissen fundoplication. To date the mainstay of GERD therapy has been
      achieved with either open or laparoscopic fundoplication or life-long medical
      treatment. Endoluminal treatment modalities attempt to augment the
      gastroesophageal junction (GEJ) function by various techniques. We searched the
      Medline database from 1980 to 2004 for studies on endoscopic GERD techniques and
      laparoscopic fundoplications. Product investigators were contacted for data
      presented in abstract form only. Endoluminal management of GERD include using
      radiofrequency energy, injection of biocompatible polymers and endoluminal
      sutures to alter the GEJ and reduce reflux. Early results while encouraging,
      should be evaluated thoroughly and with caution before widespread use can be
      advocated. Endoscopic treatment of GERD has future promise, however, more
      experience and perhaps further refinement in techniques and technology must occur
      before widespread clinical application can be encouraged.

PMID- 15494671
TI  - Current status of minimally invasive esophagectomy.
AB  - Minimally invasive esophagectomy is emerging as an option in the management of
      benign and malignant esophageal diseases. With minimally invasive esophagectomy,
      the conventional laparotomy is substituted with laparoscopy and the open
      thoracotomy with thoracoscopy. This article discusses the surgical techniques and
      outcomes for a variety of minimally invasive esophagectomy options.

PMID- 15494672
TI  - Laparoscopic antireflux surgery.
AB  - Laparoscopic antireflux surgical procedures were introduced into clinical
      practice a little more than a decade ago. Today, they constitute a well
      established treatment modality for gastro-esophageal reflux disease. With the
      introduction of laparoscopy, there has been a significant increase in the number
      of antireflux procedures performed annually in the United States. This most
      likely indicates more willingness by patients and referring physicians to
      consider the less invasive approach, rather than a change in the indications of
      surgical therapy. The main indications for surgical treatment continue to be
      relapse on medical therapy, intolerance of medications or the patient's choice of
      not taking medications chronically. A key to successful outcome following
      antireflux surgical procedures is careful patient selection and work-up. The use
      of endoscopy, contrast studies, esophageal manometry and 24-h pH studies is of
      paramount importance. Typical of many laparoscopic operations, antireflux
      procedures evolved with time and underwent several technical refinements. There
      continues to be considerable debate on some of the technical aspects of these
      procedures and on the long-term difference in outcome between partial and
      complete fundoplication. The superiority of the laparoscopic approach over the
      open approach has been established, with short-term advantages observed. Long
      term outcome between the open and laparoscopic approaches appears to be
      equivalent. Failures of surgical therapy can be broadly divided into 2 groups: 1)
      improper patient selection and work-up and 2) technical failures. Redo
      laparoscopic antireflux operations are technically challenging but feasible in
      experienced hands.

PMID- 15494673
TI  - Neoadjuvant treatment of oesophageal adenocarcinoma.
AB  - Oesophageal adenocarcinoma is an enigma. It has emerged, seemingly from nowhere,
      in the late 20th century to dominate the oesophageal oncological landscape. This
      review will examine whether the current outcome for adenocarcinoma is as good as
      it gets or whether additional treatment is necessary and if so whether
      neoadjuvant therapy is effective.

PMID- 15494674
TI  - The radical treatment of gastric carcinoma.
AB  - AIM: The aim of this paper is to review and assess the selective principles for a
      radical treatment of gastric carcinoma with respect to resection type as well as
      the role of lymphadenectomy. METHODS: From 1994 to 1999, we operated 222 patients
      affected by gastric adenocarcinoma at the 1st Surgical Clinic Institute in Padua.
      Out of the whole group, 138 patients (62.1%) underwent radical surgical treatment
      (75 patients with total gastrectomy, extended in 30 cases, and 63 patients by
      means of gastric resection). RESULTS: The overall survival rate at a median
      follow-up of 4 years was 58% for the patients treated with total gastrectomy, and
      77% in case of distal gastric resection; 97% of patients with early gastric
      cancer are alive at a median follow-up of 3 years. CONCLUSION: Whenever it is
      feasible, subtotal gastrectomy could ensure a radical treatment of gastric
      carcinoma with low morbidity and mortality rate. The survival rate of such
      patients was 77%. Prognosis of early gastric cancer is excellent. Patients with
      IV stage tumors surgically treated had a poor outcome, and they should be
      susceptible of a multidisciplinary palliative approach.

PMID- 15494675
TI  - [The surgical treatment of gastric carcinoma. Evolution in surgical technique and
      staging in a series of 194 patients].
AB  - AIM: Surgery is, at present, the only potentially curative treatment for gastric
      carcinoma. The curability depends upon the extension and localization of the
      tumor and, particularly, the lymphatic involvement and the presence of distant
      metastases. The aim of this paper is to describe the personal experience during
      the last 2 decades and analyze the results of the surgical approach which has
      changed over the time. METHODS: One-hundred and ninety-four consecutive patients
      have been reported (127 male and 67 female, with a median age of 65.8 years),
      affected by gastric carcinoma and subjected to surgical procedures from 1987 to
      2000. Because of the wide period of time which it refers to, this study is
      overlapped by a radical change in the staging rules of gastric carcinoma,
      according to the publication, in 1997, of the 5th edition of the TNM. This has
      made necessary to divide the series into 2 different groups. The 1st group is
      composed of 123 patients (63.4%), staged according to TNM-1987; the 2(nd) group
      is composed of 71 patients (36.6%) staged according to the TNM-1997. A D1
      lymphadenectomy was used as treatment protocol until 1995. Subsequently, a D2
      lymphadenectomy was performed in the most part of potentially curable patients.
      The reconstruction after total gastrectomy was carried out in all cases with Roux
      technique. In distal gastrectomies a Billroth 2 technique was performed in 89.3%
      of the cases and a Billroth 1 technique in 10.7% of the cases. RESULTS: The
      operative mortality observed on the total of patients was 1.5% (3 cases). With a
      median follow-up of 83 months (minimal 24, maximum 180 months), 134 patients were
      died, 50 are alive and 10 have been lost. The total median survival, in the 2
      groups, was 24 months. We have observed a trend to improvement of survival for
      patients with carcinoma in stage II and III operated after 1997. CONCLUSION: The
      treatment of unresectable gastric cancer, i.e. palliative surgery, is the best
      choice when possible in comparison to other surgical procedures
      (gastroenteronastomosis, jejunostomy), endoscopic procedures (dilatation,
      endoprosthesis, laser, percutaneous endoscopic gastrostomy) and medical
      therapies. In order to choose the best palliative treatment, a careful evaluation
      of the non-curability signs is necessary to avoid high risk surgical
      interventions in patients with a low expectation of life.

PMID- 15494676
TI  - [Colon recanalization after Hartmann's procedure. A challenge for the surgeon or
      a strategy to be changed?].
AB  - AIM: Restoration of colorectal continuity is the second step of the procedure
      originally described by H. Hartmann for the treatment of sigmoid colon cancers.
      It is a safe, but complex procedure, that needs a meticulous surgical technique
      and is associated with a significant morbidity in as many as 40% of cases. For
      this reason, many patients are not submitted to reversal of the colostomy.
      METHODS: The authors report their experience: 32 patients underwent colostomy
      closure after Hartmann's procedure during the last 8 years. RESULTS: The
      mortality rate was nil, but post-operative complications occurred in 12 patients
      (37.5%), namely: wound infection (11 patients) and anastomotic leak (2 patients).
      CONCLUSION: In light of this, it could be wiser to perform, in the patients
      affected with benign pathology, and in those affected with limited malignant
      pathology (T3), resection of the diseased segment of colon and primary
      anastomosis with temporary ileostomy, reserving Hartmann's procedure to patients
      unsuitable to one step treatment because of their poor general and local
      conditions.

PMID- 15494677
TI  - [Intrathoracic omentoplasty in the treatment of pleural cavity secondary to
      stabilized bronchial fistula].
AB  - AIM: The aim of this paper was to verify the effectiveness of omentoplasty,
      either single or associated to other procedures, in the treatment of permanent
      fistula of the main bronchi. METHODS: The authors report their experience of 10
      intrathoracic omentoplasties for pleural cavity from fistula of the main
      bronchus. In 2 cases a single omentoplasty was performed, while 8 patients had an
      associated procedure (4 thoracoplasties, 7 mioplasties and 2 mammoplasties). In 8
      cases the vascular pedicle used for the omentum was the right gastroepiploic
      artery, and the left one in the remaining 2 patients. The omentum was mobilized
      through an opening in the diaphragm and anchored to the bronchial stump. In the
      combined plasties it was then covered by chest wall (thoracoplasty), muscles
      (mioplasty) or mammary gland (mammoplasty); in the single omentoplasty omentum
      was also sutured to the chest wall. Indication for combined procedures was high
      bacterial contamination of the pleural cavity; single omentoplasty was performed
      for small cavities, where other procedures had previously failed. Only in the
      single omentoplasties a pre-operative selective angiography of the gastroepiploic
      arteries was performed. RESULTS: Such procedures were resolutive in 9 patients; 1
      needed an endoscopic application of fibrin glue. CONCLUSION: Intrathoracic
      omentoplasty is an effective procedure to solve both pleural cavity and
      stabilized bronchial fistula, mostly because of plastic and immunologic features
      of the omentum.

PMID- 15494678
TI  - Laparoscopic subtotal splenectomy.
AB  - AIM: Since 1979, we have studied subtotal splenectomy. This procedure has been
      used in over 180 patients to treat splenic trauma, portal hypertension, myeloid
      metaplasia due to myelofibrosis, Gaucher's disease, chronic lymphocytic leukemia,
      retarded growth and sexual development associated with splenomegaly, and
      disorders of the pancreatic tail. The aim of this study is to determine the
      feasibility, reliability and safety of the subtotal splenectomy performed by
      laparoscopic means. METHODS: An experimental study was conducted in accordance
      with the International Guiding Principles for Biomedical Research Involving
      Animals. Fourteen adult mongrel dogs of both sexes were divided into 2 groups
      (n=7): Group 1 -- laparoscopic subtotal splenectomy, preserving the upper pole
      supplied by splenogastric vessels; the splenic section, hemostasis and closure
      was done with a 45 mm linear laparoscopic surgical stapler; Group 2 -- total
      splenectomy was performed through a median laparotomy. After 3 months, we
      accomplished hematological, immunological and scintigraphic exams in all animals.
      Sections of the remnant spleens, livers and lymph nodes were histologically
      processed. RESULTS: Blood loss was minimal and all animals survived to operation
      and during the 3 months follow-up. Reduction (p<0.05) of the platelets was
      verified in Group 1. The rest of the hematological mean values remained normal.
      The remnant spleens, livers and lymph nodes showed normal histological aspects,
      with increasing amounts of polymorphonuclear cells observed in both groups.
      CONCLUSION: It is feasible and safe to perform subtotal splenectomy by
      laparoscopic means in dog.

PMID- 15494679
TI  - [Laparoscopic and general surgery guided by open interventional magnetic
      resonance].
AB  - Interventional magnetic resonance (IMR) machines have produced unique opportunity
      for image-guided surgery. The open configuration design and fast pulse sequence
      allow virtual real time intraoperative scanning to monitor the progress of a
      procedure, with new images produced every 1.5 sec. This may give greater
      appreciation of anatomy, especially deep to the 2-dimensional laparoscopic image,
      and hence increase safety, reduce procedure magnitude and increase confidence in
      tumour resection surgery. The aim of this paper was to investigate the
      feasibility of performing IMR-image-guided general surgery, especially in
      neoplastic and laparoscopic field, reporting a single center -- St. Mary's
      Hospital (London, UK) -- experience. Procedures were carried out in a Signa 0.5 T
      General Elettric SP10 Interventional MR (General Electric Medical Systems,
      Milwaukee, WI, USA) with magnet-compatible instruments (titanium alloy
      instruments, plastic retractors and ultrasonic driven scalpel) and under general
      anesthesia. There were performed 10 excision biopsies of palpable benign breast
      tumors (on female patients), 3 excisions of skin sarcoma (dermatofibrosarcoma
      protuberans), 1 right hemicolectomy and 2 laparoscopic cholecystectomies. The
      breast lesions were localized with pre- and postcontrast (intravenous gadolinium
      DPTA) sagittal and axial fast multiplanar spoiled gradient recalled conventional
      Signa sequences; preoperative real time fast gradient recalled sequences were
      also obtained using the flashpoint tracking device. During right hemicolectomy
      intraoperative single shot fast spin echo (SSFSE) and fast spoiled gradient
      recalled (FSPGR) imaging of right colon were performed after installation of 150
      cc of water or 1% gadolinium solution, respectively, through a Foley catheter;
      imaging was also obtained in an attempt to identify mesenteric lymph nodes
      intraoperatively. Concerning laparoscopic procedures, magnetic devices
      (insufflator, light source) were positioned outside scan room, the tubing and
      light head being passed through penetration panels. Intraoperative MR
      cholangiography was performed using fast spin echo (SSFSE) techniques with
      minimal intensity projection 3-dimensional reconstruction. About skin sarcomas, 2
      of them were skin recurrences of previously surgically treated sarcomas (all of
      them received preoperative biopsy) and the extent of the lesion was then
      determined using short tau inversion recovery (STIR) sequence. The skin was
      closed in each case without need for any plastic reconstruction. The breast
      lesions were visualized with both Signa and real-time imaging and all enhanced
      with contrast: 2 (20%) were visualized only after contrast enhancement;
      intraoperative real time imaging clearly demonstrated a resection margin in all
      cases. Maximum dimensions of breast specimens (range 8-50 mm, median 24.5 mm)
      were not significantly different from those measured by Signa (p>0.17, Student's
      paired t-test) or real time images (p>0.4): also there was no significant
      difference in lesion size between Signa and real time images (p>0.25). All
      postprocedure scans clearly demonstrated complete excision. The extent of the
      tumor at MR imaging was greater in each case than suggested by clinical
      examination. Adequate resection margins were planned using STIR sequences.
      Histological examination confirmed clear surgical margins of at least 1 cm in
      each case. During right hemicolectomy, both intraoperative SSFSE and FSPGR
      contrast imaging revealed the lesion and details of the colonic surface; imaging
      of the lymph node draining right colon was only partially successful, due to
      movement artifact. Concerning laparoscopic procedures, both FSE and SSFSE
      techniques produced reasonable images of the gallbladder and intrahepatic ducts,
      but the FSE imaging was of poor quality due to respiration artifact; however,
      SSFSE allowed visualization of the gallbladder and part of the common bile duct.
      About skin sarcomas, the extent of the tumor at MR imaging was greater in each
      case than suggested by clinical examination and in each case the complete tumor
      excision was confirmed. Histological examination confirmed clear surgical margins
      of at least 1 cm in each case. Intraoperative MR scanning reliably identifies
      palpable breast tumours and skin sarcomas and is sufficiently accurate to guide
      their surgical excision. Further work may be done to develop laparoscopic and
      open abdominal surgery as well.

PMID- 15494680
TI  - [Two cases of small bowel ischemia due to unusual cause].
AB  - The authors report 2 cases of small bowel ischemia due to unusual cause. In both
      cases, vasculopathy was the cause of ischemia, but with a different etiology. In
      the first case, a mesenteric inflammatory veno-occlusive disease, with striking
      features of extensive phlebitis and venulitis affecting the veins of the small
      intestine and mesentery, without arterial involvement of this district was
      observed and histological examination showed inflammatory lymphocytic infiltrates
      and myointimal hyperplasia of the veins. The second case affected by intestinal
      ischemia from secondary and multiple cholesterol embolism, the histological
      examination showed inflammatory infiltrates with (lymphocytes and granulocytes)
      in the vessels of submucosal mesenteric area, by loose intimal fibrosis
      incorporating cholesterol clefts. Both patients required surgical exploration
      with resection of ischemic bowel. In the second case laparoscopy was the initial
      approach which allowed to identify the extension of ischemia with special regard
      to the perforation. The ultimate diagnosis is possible only with histological
      examination. Clinically, patients show the general signs of intestinal ischemia
      with pain, vomiting and bloody diarrhea. Prognosis depends on the extension of
      the lesions and the early surgical treatment.

PMID- 15494681
TI  - [The surgeons civil responsibility insurance].
AB  - After a short research in the field national insurances, the author analyses the
      professional physician insurance policy; the ambiguity and difficulty of
      contracts concerning the professional health activity of surgeon, whether as
      state employee or as independent professional are pointed put. With the
      introduction of the ministerial decree dated January 29,1992, the new labour
      agreement, the privacy law, the evolution of ''informed consent'', the esthetic
      injury concept, the safety regulations law and the administrative liability,
      surgeons must pay attention to draw up an insurance policy suitable to their
      profession.

PMID- 15494682
TI  - The WHO classification of the myelodysplastic syndromes.
AB  - For more than two decades the French-American-British (FAB) classification has
      provided a framework for the diagnosis and classification of the myelodysplastic
      syndromes. However, with widespread use of this classification, it became clear
      that prognostic differences existed within single categories. The FAB
      classification has therefore been modified by a World Health Organization (WHO)
      expert group to take account of these prognostic differences. In addition,
      therapy-related myelodysplasia and the 5q- syndrome have been recognized as
      distinct types of disorder and the existence of mixed
      myelodysplastic/myeloproliferative disorders has been recognized; chronic
      myelomonocytic leukaemia, previously regarded as one of the myelodysplastic
      syndromes, was re-assigned to this latter group of disorders.

PMID- 15494684
TI  - Role of osteopontin in adhesion, migration, cell survival and bone remodeling.
AB  - Osteopontin (OPN) is a secreted adhesive glycophosphoprotein expressed by several
      cell types. It is normally produced in bone, teeth, kidney and epithelial lining
      tissues and is found in plasma and breast milk. It is involved in a number of
      physiologic and pathologic events including angiogenesis, apoptosis,
      inflammation, wound healing and tumor metastasis. In this review focus will be on
      OPN in bone and its role in adhesion, migration and cell survival. These aspects
      of OPN biology are important in tumorigenesis.

PMID- 15494683
TI  - Role of the nuclear matrix proteins in malignant transformation and cancer
      diagnosis.
AB  - The nuclear matrix (NM) is the structural framework of the nucleus that consists
      of the peripheral lamins and pore complexes, an internal ribonucleic protein
      network, and residual nucleoli. Differences between the nuclear matrix protein
      (NMP) composition of transformed cells and their normal homologues were detected
      in numerous cases. Actually several tumor-specific nuclear matrix proteins (NMPs)
      are proposed for diagnostic of bladder, breast, colon and some other cancers.
      According to the role of NMPs in development and phenotype of a given neoplasms
      the tumors can be classified as follows: I. Tumors bearing mutations in the genes
      encoding NMPs. The group consists of following subgroups: 1) hereditary cancer
      syndromes with mutations in the NM-attached oncoproteins or tumor suppressor
      genes; 2) sporadic tumors with somatic mutations in the NM-attached oncoproteins,
      tumor suppressor genes or replication enzymes; 3) leukemias with fused NMPs. II.
      Tumors with phenotypic quantitative or qualitative changes of the NMP spectrum.

PMID- 15494685
TI  - Monotherapy in advanced prostate cancer: an overview.
AB  - Prostate cancer is the second leading malignancy in men associated with an
      enormous research interest in all aspects of the disease. It is well recognized
      that the regulation of prostatic growth is a complicated biological process.
      Further more the androgenic dependence of the advanced prostate cancer is well
      know and in the last 50 years significant progresses regarding the principle of
      deprivation of androgens for the treatment of the disease occured. Prostate
      cancer is now diagnosed in earlier stages and treatment results in increased
      potential for cure or extension of overall survival. Unfortunately, every
      treatment for prostate cancer has adverse effects with negative impact in health
      related quality of life. Surgical or pharmacological castration has a significant
      negative impact on quality of life in patients with prostate cancer (loss of
      sexuality, osteoporosis, and loss of muscle mass, e.g.). Antiandrogen monotherapy
      is considered to be a treatment in well-informed patients who wish to remain
      sexually active, can be administered orally, and is well tolerated by patients
      with prostate cancer. This review is focused on antiandrogen monotherapy in the
      treatment of advanced prostate cancer.

PMID- 15494686
TI  - Managing cancer patients with acute venous thromboembolism: exploring safe
      alternatives to hospitalisation.
AB  - Acute venous thromboembolism (VTE) is a common and potentially fatal complication
      that frequently occurs in cancer patients. Few data are currently available about
      the optimal management of this category of high-risk patients. In clinical
      practice, physicians have to deal with many problems related to cancer patients
      with acute VTE. For instance, cancer patients with deep vein thrombosis (DVT) are
      frequently admitted to the hospital since their high rate of recurrent thrombotic
      events and/or bleeding-related therapy; however, most of them would prefer
      alternatives to prolonged hospitalisation. Then, it is not clearly whether data
      coming from a non-cancer population (such as that regarding the use of D-dimer
      test and/or pre-test clinical probability [PCP]), can be reliable applied in
      cancer patients. Finally, scanty information is present on the feasibility of the
      "home-treatment program" for DVT in this category of high-risk patients. In our
      review we present data on a population of cancer patients evaluated at the
      Emergency Care in whom we have evaluated: 1) the diagnostic accuracy of PCP and D
      dimer test; 2) the safety and efficacy of low molecular weight heparins (LMWH) as
      "protective anticoagulation" in case of deferred imaging for VTE and 3) the
      safety and efficacy of home treatment.

PMID- 15494687
TI  - Peculiarities of molecular events in human glial tumors revealed by serial
      analysis of gene expression (SAGE).
AB  - AIM: To enhance glioblastoma (GB) marker discovery we compared gene expression in
      glioblastoma with human normal brain (NB). METHODS: Serial analysis of gene
      expression (SAGE) was used to determine the genes differentially expressed
      between glioblastoma and human NB by accessing SAGEmap NCBI web site. RESULTS: Of
      117 genes with more than 5-fold difference (P less, not similar 0.05) found by
      comparison of five GB vs. two NB SAGE libraries, 24 had an increased expression
      in GB. High expression of 10 genes in GB as well as in GB cell lines suggested
      that expression in the bulk tumors originated from transformed cells. CONCLUSION:
      Since the highest expression levels of these 24 genes were mostly found in GB,
      they can be viewed as molecular markers in the analysis of malignant progression
      of astrocytic tumors.

PMID- 15494688
TI  - Genetic analysis of microsatellite markers in patients from hereditary
      nonpolyposis colorectal cancer (HNPCC) families.
AB  - AIM: Microsatellite instability (MSI) is due to defective DNA mismatch repair
      (MMR) and is characteristic of hereditary nonpolyposis colorectal cancer (HNPCC)
      tumors. The role of MSI in familial predisposition to colorectal cancer was
      investigated in this study by both microsatellite analysis and mutation screening
      of the two major MMR genes MLH1 and MSH2 among familial cases. METHODS: PCR-based
      microsatellite analysis was performed in blood obtained from 30 members from
      HNPCC families. Blood samples age matched healthy individuals (n = 28) served as
      control. MSI was studied at five loci containing single- or dinucleotide repeat
      sequences and mapping to different chromosomal locations: BAT-25 (at locus 4q12),
      BAT-26 (2p16), D2S123 (2p16-p21), D5S346 (5q21-q22) and D17S250 (17q11.2-q12).
      RESULTS: MSI frequency was higher in member of HNPCC families [7/30 (23%)] than
      in control [3/28 (10.7%)] cases. Two MLH1 and one MSH2 mutations were identified
      in 7 MSI positive samples from HNPCC families. MLH1/MSH2 mutations were only in
      MSI high samples detected. CONCLUSION: Genetic alterations seem to be a risk
      factor of colorectal cancer in subjects belonged to HNPCC families with high
      incidence of this cancer.

PMID- 15494689
TI  - Signal transduction pathways in Burkitt's lymphoma cell lines BL41 and DG75 with
      different sensitivity to doxorubicin.
AB  - AIM: To understand the biochemical basis of cell sensitivity to cytotoxic effect
      of doxorubicine (DOX), we investigated signaling cascades mediated by c-Jun N
      terminal protein kinases (JNK1/2), p38 mitogen-activated protein kinases (MAPK),
      extracellular signal-regulated protein kinase (ERK1/2) and protein kinase B/Akt
      in both DOX-sensitive BL41 and the DOX-resistant DG75 Burkitt's lymphoma (BL)
      cell lines. METHODS: To test the effect of DOX on different signaling cascades,
      BL41 and DG75 cells were treated with DOX for varying lengths of time. Cytotoxic
      effect of DOX was analyzed by Hoechst 33342 staining. Total amount of JNK1/2,
      ERK1/2, p38 MARK, Akt proteins, and also phosphorylated/activated forms of these
      enzymes were detected using Western blot analysis with specific antibodies.
      Immunophenotypic analysis of BL41 and DG75 cells was performed by indirect
      immunofluorescence staining. RESULTS: Our findings demonstrated that DOX
      treatment of the BL41 cells led to sustained activation of JNK1/2 and p38 MAPK.
      This activation/phosphorylation did not result from increased expression of
      either JNK1/2 or p38 MAPK since protein levels of JNK1/2 and p38 MAPK in DOX
      treated and untreated cells were unaltered. Apoptotic signaling cascade induced
      by DOX in BL41 cell was accompanied by Akt dephosphorylation. The effect of DOX
      in drug-resistant cell line DG75 convoyed by dephosphorylation of JNK1/2, p38
      MAPK and activation of Akt. Fate of BL cells did not depend from ERK activity.
      CONCLUSION: The outcome of cellular response to DOX in BL cell lines is
      determined by interference of at least three signaling pathways: JNK1/2, p38 MAPK
      and PKB/Akt. The balance between Akt/PKB and MAPK pathways is important in
      determining whether BL cells survive or undergo apoptosis in response to DOX
      treatment.

PMID- 15494690
TI  - Correlation between generation of nitric oxide and cell viability in human
      peripheral blood mononuclear cells and leukemic Jurkat T-cell line.
AB  - AIM: To measure nitric oxide (NO) production in the form of nitrite derivative in
      relation to cell viability and apoptosis development in human peripheral blood
      mononuclear cells compared to that processes in human leukemic Jurkat T-cell
      line. METHODS: Apoptosis was induced by dexamethasone (1 microg/ml) or NaNO(2) (7
      microg/ml) added in the presence or absence of NO-synthase inhibitor N(omega)
      nitro-L-arginine methyl ester (L-NAME) (27 microg/ml) during cell culturing. Cell
      viability was determined by trypan blue assay. Apoptosis was measured using DNA
      "ladder" assay. RESULTS: Dexamethazone and NaNO(2) were shown to cause DNA
      "laddering" in both cell types. L-NAME prevented the appearance of apoptosis in
      both normal mononuclear cells of peripheral blood and leukemic Jurkat T-cell in
      the case of dexamethasone action, but it could not prevent it in the case of
      NaNO(2) action. The results of cell viability showed that both the dexamethasone
      and NaNO(2) significantly increased the percentage of dead cells. Their effect
      was better expressed in Jurkat T-cell line. The levels of nitrite production were
      higher in the leukemic T-cells comparing to such levels in the normal mononuclear
      cells. CONCLUSION: Strong positive correlation was demonstrated between NO
      production and apoptosis development in both studied cell types, however leukemic
      Jurkat T-cell line responses were better expressed than such responses in normal
      mononuclear cells of peripheral blood. Potential significance of that correlation
      as well as possible mechanisms of appearing differences are discussed.

PMID- 15494691
TI  - Role of polyamines in the function of nuclear transcription factor NF-kappaB in
      breast cancer cells.
AB  - The aim of the work was the investigation of the influence of polyamines on
      formation of nuclear transcription factor kappa B (NF-kappaB) complex with
      specific DNA-sequences nuclear response elements (NRE), and the study of content
      of p50 and p65 (NF-kappaB subunits) in breast tumor cells under polyamines
      metabolism modulation. METHODS: The model experiments in vitro were carried out
      on cultured MCF-7 cells, in vivo experiments -- on experimental Ca755 and Walker
      256 tumors using surface plasmon resonance (SPR) and Western-blotting analysis.
      RESULTS: The data have demonstrated that polyamines falicitated p50 -- NRE
      binding. Under conditions of polyamine depletion, an increase of content of both
      p50 and p65 subunits of NF-kappaB in the nucleus has been registered (especially
      that of p50 subunits). Upon addition of alpha-DFMO + putrescine to the culture
      medium of MCF-7 cells, the decrease of the levels of p50 and p65 proteins in the
      nuclei has been observed. CONCLUSION: Polyamines influence the activity of NF
      kappaB transcription factor in breast tumor cells.

PMID- 15494692
TI  - Uptake and phototoxicity of tricarbocyanine indolenine dye covalently bound with
      glucose (TICS) under acidification of tumor cells environment.
AB  - AIM: To evaluate the influence of pH on accumulation and photocytotoxicity of the
      novel tricarbocyanine indolenine dye covalently bound with glucose (TICS).
      METHODS: For in vitro experiments, cultured HeLa cells were incubated with TICS
      at pH 7.1, 6.5 or 6.2 and then scored for dye uptake, viability and sensitivity
      to laser (740 nm) irradiation. In vivo TICS was injected to rats with implanted
      subcutaneously SM-1 tumor and then dye accumulation and tumor necrosis depth
      after laser irradiation were defined. RESULTS: Reduction of medium pH in vitro
      was shown to increase in cellular TICS contents and to enhance as its "dark"
      cytotoxicity, and photocytotoxicity. The ratio of "dark" cytotoxicity to
      photocytotoxicity parameters increased 2-fold with decreasing pH value. In vivo
      infusion of glucose (10 g/kg) to rats resulted in improved selectivity of TICS
      accumulation and increase in tumor necrosis depth after laser irradiation.
      CONCLUSION: pH reduction of tumor cells environment improves efficacy of
      photodynamic treatment with TICS.

PMID- 15494693
TI  - Total proteolytic activity and content of the main proteinase inhibitors in blood
      plasma of rats bearing doxorubicin-sensitive and doxorubicin-resistant Guerin
      carcinoma.
AB  - The AIM of work was to evaluate the alteration of the total proteolytic activity
      (TPA) and the levels of alpha(1)-proteinase inhibitor (alpha1PI) and alpha(2)
      macroglobuline (alpha2M) in blood plasma of rats bearing Guerin carcinoma upon
      the development of Doxorubicin (DOX) resistance. MATERIALS AND METHODS: TPA and
      alpha1PI and alpha2M content in the blood plasma of male Wistar rats bearing DOX
      resistant and DOX-sensitive Guerin carcinoma were evaluated by standard
      biochemical methods. RESULTS: During growth of both DOX-sensitive and DOX
      resistant Guerin carcinoma, TPA decrease in blood plasma and the increase of
      alpha1PI levels were registered; in DOX-resistant group this effect was more
      pronounced. Alpha2M content in blood plasma of animals from both experimental
      groups was considerably smaller than that of the control and was the lowest in
      DOX-resistant group. CONCLUSION: The growth of DOX-resistant Guerin carcinoma is
      accompanied by imbalance of proteolysis processes in the blood plasma,
      particularly, alteration of TPA and alpha1PI and alpha2M levels.

PMID- 15494694
TI  - Determination of optimum planning target volume margins for various tumor sites
      using electronic portal imaging.
AB  - OBJECTIVE: The aim of this study is to evaluate the efficacy of electronic portal
      imaging (EPI) to measure the set-up errors for four different sites of
      irradiation caused by patient positioning. METHODS: A total number of 95 portal
      images of 11 patients (3 pelvic, 1 total cranium, 3 mantle and 4 tangential
      fields for breast) were collected during the course of study. The first portal
      images after a correction of set-up errors according to the simulation films were
      accepted as the reference images for the subsequent sessions. By matching each
      portal image with the reference image, the deviations in lateral (x) and superior
      inferior (y) axis for all and additionally in antero-posterior (z) axis for
      pelvis, and standard deviations were calculated. RESULTS: The set-up errors
      caused by patient's positioning are completely abolished in 15 mm planning target
      volume (PTV) margins for all studied cases. CONCLUSION: Standard PTV margins
      usually completely cover the set-up errors caused by patient's positioning.

PMID- 15494695
TI  - Evaluation of cisplatin-DNA crosslinks formation with UV-C application by the
      alkaline Comet-assay.
AB  - The AIM of the present study was to investigate DNA damage induced by widely
      applied anticancer preparation cisplatin (cis-DDP) at doses comparable with
      therapeutic ones in leukocytes of healthy donors. METHODS: DNA damage and repair
      was estimated by the single cell gel electrophoresis or Comet-assay. For
      estimation of cis-DDP-induced DNA crosslinks the combined treatment by cis-DDP
      with the DNA damaging agent UV-C was used. The RESULTS obtained indicate that cis
      DDP is forming crosslinks with DNA in human leukocytes and significantly reduce
      UV-C-induced DNA migration. CONCLUSION: The Comet-assay with UV-C application is
      a useful tool to detect cis-DDP- induced DNA crosslinks. Data on the cis-DDP
      induced DNA damage in vitro may be important for their extrapolation on in vivo
      level.

PMID- 15494696
TI  - Antitumor reactivity of splenocytes primed in vivo with dendritic-cell-based
      vaccine and secondarily activated with a cocktail of cytokines in vitro.
AB  - AIM: To evaluate the antitumor reactivity of splenocytes primed in vivo with
      dendritic cell (DC) based vaccine and secondarily activated with cocktail of
      cytokines in vitro. METHODS: Tumor lysate pulsed DC were used to generate
      effector T cells in the murine L615 leukemia model. DC were induced and pulsed
      with tumor lysate. The splenocytes from the DC based vaccine primed mice were
      termed VPS. Some VPS were activated with anti-CD3 alone (VPS-CD3), the other
      cells were activated with a cocktail of cytokines including IFN-gamma, IL-1beta,
      anti-CD3 and IL-2 (VPSC). RESULTS: Both VPS and VPS-CD3 showed moderate IFN-gamma
      release to stimulatory tomor cells in vitro and antitumor capacity in vivo.
      However, VPSC showed much higher IFN-gamma release and far superior antitumor
      capacity than the other cells in this leukemia model. CONCLUSION: The result here
      indicates that tumor lysate pulsed DC can be used as a strategy to generate
      effector T cells which can be further activated with a cocktail of cytokines for
      adoptive immunotherapy.

PMID- 15494697
TI  - Breast carcinoma metastasis to the orbit and paranasal sinuses: a case report.
AB  - This is the case of a 34 years old female patient, with known history of
      disseminated, invasive, ductal adenocarcinoma, grade II, of the left breast, who
      presented with two distinct localizations of metastasis affecting the orbits. One
      in the right orbit and a second one in the frontal sinuses, the latter
      infiltrating the cognate ethmoid, exerting pressure on the inner wall of the left
      orbit. We present the symptoms, the ophthalmic signs and the imaging techniques
      that aided the localization of these metastasis, while literature review shows
      that such combination is rare.

PMID- 15494704
TI  - Pulmonary hypertension.
AB  - Pulmonary hypertension, in its simplest sense, is elevation of the pulmonary
      artery pressure above normal. A multitude of diseases may increase the pulmonary
      artery pressure and result in right ventricular dysfunction. The treatments of
      pulmonary hypertension are as varied as its causes. The past decade has realized
      remarkable growth in knowledge of the mechanisms of pulmonary arterial
      hypertension and, concurrently, therapies for this once uniformly fatal disease.
      In addition to continuous intravenous epoprostenol, subcutaneous treprostinil and
      oral bosentan are now FDA approved for the treatment of pulmonary arterial
      hypertension. Other forms of pulmonary hypertension, such as pulmonary venous
      hypertension, pulmonary hypertension related to diseases of the respiratory
      system, and thromboembolic pulmonary hypertension will be discussed.

PMID- 15494705
TI  - A genome-wide scan points to a susceptibility locus for bipolar disorder on
      chromosome 12.
AB  - Our previous results pointed to a putative gene for susceptibility to bipolar
      affective disorder located on the chromosomal region 12q23-q24 that segregated in
      the Saguenay-Lac-St-Jean population of Quebec. We report here results from a
      second genome-wide scan based on the analysis of 380 polymorphic microsatellite
      markers. For the purpose of this analysis, an additional 18 families were
      recruited from the Saguenay-Lac-St-Jean region and pooled to our previous sample
      to improve its statistical power, giving a total of 394 sampled individuals. This
      work confirms the presence of a susceptibility locus for affective disorder on
      chromosome 12q24 with parametric LOD score value of 3.35 at D12S378 when
      pedigrees were broken into nuclear families and analysed under a recessive
      segregation model. This result was supported by neighbouring markers and by a LOD
      score value of 5.05 at D12S378 under model-free analysis. Other regions of lower
      interest were indicated on chromosomes 2, 5, 7, 9, 10, 17 and 20.

PMID- 15494706
TI  - IDO and interferon-alpha-induced depressive symptoms: a shift in hypothesis from
      tryptophan depletion to neurotoxicity.
AB  - Studies show that administration of interferon (IFN)-alpha causes a significant
      increase in depressive symptoms. The enzyme indoleamine 2,3-dioxygenase (IDO),
      which converts tryptophan (TRP) into kynurenine (KYN) and which is stimulated by
      proinflammatory cytokines, may be implicated in the development of IFN-alpha
      induced depressive symptoms, first by decreasing the TRP availability to the
      brain and second by the induction of the KYN pathway resulting in the production
      of neurotoxic metabolites. Sixteen patients with chronic hepatitis C, free of
      psychiatric disorders and eligible for IFN-alpha treatment, were recruited.
      Depressive symptoms were measured using the Montgomery Asberg Depression Rating
      Scale (MADRS). Measurements of TRP, amino acids competing with TRP for entrance
      through the blood-brain barrier, KYN and kynurenic acid (KA), a neuroprotective
      metabolite, were performed using high-performance liquid chromatography. All
      assessments were carried out at baseline and 1, 2, 4, 8, 12 and 24 weeks after
      treatment was initiated. The MADRS score significantly increased during IFN-alpha
      treatment as did the KYN/TRP ratio, reflecting IDO activity, and the KYN/KA
      ratio, reflecting the neurotoxic challenge. The TRP/CAA (competing amino acids)
      ratio, reflecting TRP availability to the brain, did not significantly change
      during treatment. Total MADRS score was significantly associated over time with
      the KYN/KA ratio, but not with the TRP/CAA ratio. Although no support was found
      that IDO decreases TRP availability to the brain, this study does support a role
      for IDO activity in the pathophysiology of IFN-alpha-induced depressive symptoms,
      through its induction of neurotoxic KYN metabolites.

PMID- 15494708
TI  - High-grade dysplasia associated with fundic gland polyposis in a familial
      adenomatous polyposis patient, with special reference to APC mutation profiles.
AB  - We report a patient with familial adenomatous polyposis who developed high-grade
      dysplasia against a background of fundic gland polyposis. Two large high-grade
      dysplasia lesions were found in the gastric body, where numerous fundic gland
      polyps were present. In both lesions, the dysplastic epithelium covered non
      neoplastic oxyntic glands that occasionally exhibit cystic changes. A genetic
      analysis for APC (adenomatous polyposis coli) revealed a somatic 50-bp deletion
      involving codons 1502-1517 and 2-bp deletion at codon 1465 in each lesion of high
      grade dysplasia. In contrast, six of the 18 fundic gland polyps were found to
      harbor an identical mutation: 1-bp insertion at codon 1556. Both lesions of high
      grade dysplasia and the fundic gland polyps were similarly located in the fundic
      gland area and were caused by the inactivation of APC; however, their mutation
      profiles of APC were different. These results imply that fundic gland polyps and
      high-grade dysplasia of the stomach have distinct preferences for APC genotypes
      in their development.

PMID- 15494707
TI  - Hyperprolinemia is a risk factor for schizoaffective disorder.
AB  - DNA sequence variations within the 22q11 DiGeorge chromosomal region are likely
      to confer susceptibility to psychotic disorders. In a previous report, we
      identified several heterozygous alterations, including a complete deletion, of
      the proline dehydrogenase (PRODH) gene, which were associated with moderate
      hyperprolinemia in a subset of DSM III schizophrenic patients. Our objective was
      (i) to determine whether hyperprolinemia is associated with increased
      susceptibility for any of three psychiatric conditions (schizophrenia,
      schizoaffective disorder and bipolar disorder) and (ii) to establish a
      correlation between hyperprolinemia and PRODH genotypes. We have conducted a case
      control study including 114 control subjects, 188 patients with schizophrenia, 63
      with schizoaffective disorder and 69 with bipolar disorder. We report that,
      taking into account a confounding effect due to valproate treatment,
      hyperprolinemia is a risk factor for DSM IIIR schizoaffective disorder (P=0.02,
      Odds ratio=4.6, 95% confidence interval 1.3-16.3). We did not detect 22q11
      interstitial deletions associated with the DiGeorge syndrome among the 320
      patients of our sample and we found no association between common PRODH
      polymorphisms and any of the psychotic disorders. In contrast, we found that five
      rare PRODH alterations (including a complete PRODH deletion and four missense
      substitutions) were associated with hyperprolinemia. In several cases, two
      variations were present simultaneously, either in cis or trans in the same
      subject. A total of 11 from 30 hyperprolinemic subjects bore at least one genetic
      variation associated with hyperprolinemia. This study demonstrates that moderate
      hyperprolinemia is an intermediate phenotype associated with certain forms of
      psychosis.

PMID- 15494709
TI  - Human herpesvirus-6-associated acute lymphadenitis in immunocompetent adults.
AB  - In contrast to other causes of herpetic lymphadenitis, the histological features
      associated with human herpesvirus-6 (HHV-6) infection have remained elusive since
      its discovery in 1986. We describe the histologic and phenotypic changes
      associated with acute HHV-6 lymphadenitis in two immunocompetent adults who
      presented with fever, fatigue, generalized lymphadenopathy, and elevated liver
      enzymes. Serologic tests for human immunodeficiency virus, acute Epstein-Barr
      virus, and cytomegalovirus infection were negative. Lymph node biopsies were
      consistent with viral lymphadenitis. Intranuclear and cytoplasmic inclusions were
      identified in CD4-positive T lymphocytes in expanded paracortical areas.
      Immunohistochemical staining with monoclonal antibody to the HHV-6 gp60/110 kDa
      envelope glycoprotein showed that the inclusions were positive for viral antigen.
      Electron microscopy demonstrated numerous viral particles in the cytoplasm and
      nucleus, characteristic of Herpesviridae family. Clustering of viral particles
      was observed, which has previously been reported only in infected tissue culture
      cells. PCR followed by sequencing of DNA extracted from the lymph nodes
      identified the virus as HHV-6, type B. This is the first report that documents
      distinctive histologic features of HHV-6 lymphadenitis and demonstrates that the
      cells harboring the virus in vivo are CD4-positive T lymphocytes.

PMID- 15494710
TI  - Primary synovial sarcoma of the heart: a cytogenetic and molecular genetic
      analysis combining RT-PCR and COBRA-FISH of a case with a complex karyotype.
AB  - Synovial sarcomas usually occur in the soft tissues of the extremities of
      adolescents and middle-aged patients, in the vicinity of large joints. We present
      a patient with a synovial sarcoma of the left atrium and ventricle, which is an
      extremely rare location. Diagnosis was confirmed by reverse transcriptase
      polymerase chain reaction (RT-PCR), showing the t(X;18) fusion transcript. With a
      multicolor COmbined Binary RAtio labeling Fluorescence In Situ Hybridization
      (COBRA-FISH) technique, a complex karyotype evolved with identification of
      derivative chromosomes with multiplex rearrangements. This underscores the
      importance of molecular analysis of spindle cell tumors in unusual locations.
      Moreover, it shows that the presumed diagnostic translocation t(X;18) can be
      embedded in a sequence of other chromosomal rearrangements of which the function
      is as yet unknown.

PMID- 15494711
TI  - A distinct expression pattern and point mutation of c-KIT in papillary renal cell
      carcinomas.

PMID- 15494715
TI  - Intraepithelial CD8+ T-cell-count becomes a prognostic factor after a longer
      follow-up period in human colorectal carcinoma: possible association with
      suppression of micrometastasis.
AB  - T-cell infiltration into human cancer tissues can be a manifestation of host
      immune responses to cancer cells. The present study was undertaken to explore the
      clinicopathological significance of intraepithelial CD8(+) T cells using 371
      consecutively sampled human colorectal carcinomas. By univariate analysis, we
      noted that the survival curves by intraepithelial CD8(+) T cells became separated
      only after 1 to 2 years postoperation. Multivariate analyses revealed that the
      beneficial effect of this factor becomes significant only after a longer (more
      than 2 year), but not after a shorter (less than 2 year) follow-up period.
      Furthermore, the number of intraepithelial CD8(+) T cells was significantly
      higher in patients alive for more than 5 years than in patients who either died
      of cancer after a curative operation or patients who underwent a noncurative
      operation. Patients' cancer-specific death long after a curative operation is
      thought to be caused by the growth of micrometastases in other organs or near the
      primary sites. The effects of intraepithelial CD8(+) T cells, therefore, may be
      mediated by suppression of micrometastasis, rather than suppression of growth in
      the primary tumour. In conclusion, our data support a hypothesis on the presence
      of systemic immunosurveillance against micrometastasis of cancer cells.

PMID- 15494716
TI  - Phase I/II study of DHA-paclitaxel in combination with carboplatin in patients
      with advanced malignant solid tumours.
AB  - DHA-paclitaxel is a conjugate of paclitaxel and the fatty acid, docosahexaenoic
      acid. Preclinical studies have demonstrated increased activity, relative to
      paclitaxel, with the potential for an improved therapeutic ratio. We conducted a
      phase I study to determine the maximum tolerated doses of DHA-paclitaxel and
      carboplatin when administered in combination. Two cohorts of patients were
      treated: carboplatin AUC 5 with DHA-paclitaxel 660 mg m(-2) and carboplatin AUC 5
      with DHA-paclitaxel 880 mg m(-2). Both drugs were given on day 1 every 21 days. A
      total of 15 patients were enrolled with a median age of 59 years (range 33-71).
      All patients had advanced cancer refractory to standard treatment, performance
      status 0-2 and were without major organ dysfunction. A total of 54 cycles of
      treatment were delivered. No dose-limiting toxicity (DLT) was seen in the first
      cohort of three patients. In an expanded second cohort, neutropenia was the main
      DLT, occurring in the first cycle of treatment in five of 12 patients: three of
      these patients and one additional patient also experienced dose-limiting grade 3
      transient rises in liver transaminases. No alopecia was seen and one patient
      developed clinically significant neuropathy. One partial response was seen in a
      patient with advanced adenocarcinoma of the oesophago-gastric junction and 12
      patients had stable disease with a median time to progression of 184 days (range
      60-506 days). The recommended phase II dose in pretreated patients is Carboplatin
      AUC 5 and DHA-paclitaxel 660 mg m(-2) given every 21 days. Further studies with
      Carboplatin AUC 5 and DHA-paclitaxel 880 mg m(-2), given every 28 days, are
      warranted in chemo-naive patients.

PMID- 15494717
TI  - Clusterin overexpression in both malignant and nonmalignant prostate epithelial
      cells induces cell cycle arrest and apoptosis.
AB  - Expression of the castration-induced clusterin protein is incompatible with the
      survival of human prostate cancer cells in tissues and in cell culture. To
      investigate the fate of human prostate epithelial cells, when engineered to
      maintain expression of clusterin protein, we have used an IRES-hyg vector and
      hygromycin selection. PC-3 prostate tumour cells were substantially more
      sensitive to clusterin expression than nonmalignant PNT1a cells, showing multiple
      phenotypic changes including cell cycle arrest and increased apoptosis. The
      results strengthen the hypothesis that clusterin expression is proapoptotic.
      Expression of exogenous clusterin in both cell types resulted in its relocation
      from the cytoplasm and a nuclear accumulation of the protein, as was also seen in
      the same cells when apoptosis was induced by etoposide treatment. To survive
      clusterin expression, the PC-3 tumour cells developed apoptosis-inhibitory
      properties. This could have significance for the resistance of prostate cancers
      to chemo/radiotherapy, where clusterin overexpression is observed.

PMID- 15494718
TI  - Tyrosine kinase inhibitor AG1024 exerts antileukaemic effects on STI571-resistant
      Bcr-Abl expressing cells and decreases AKT phosphorylation.
AB  - Chronic myelogenous leukaemia (CML) is a clonal malignancy of the pluripotent
      haematopoietic stem cell, characterised by an uncontrolled proliferation and
      expansion of myeloid progenitors expressing a fusion oncogene, BCR-ABL, the
      molecular counterpart of the Ph1 chromosome. The tyrosine kinase (TK) activity of
      BCR-ABL is known to activate several major signalling pathways in malignant
      cells, including Ras, JAK/STAT and PI3K/Akt with evidence of proteasome-mediated
      degradation of other targets such as the DNA repair protein DNA-PKcs and cyclin
      dependent kinases inhibitor p27. Targeting these abnormalities by blocking TK of
      BCR-ABL with STI571 provided a promising approach for the therapy of CML. The
      recent development of resistance to STI571 illustrates, however, that the use of
      other TK inhibitors could be of major interest for therapeutic purposes. To this
      end, the TK inhibitor Tyrphostin AG1024 was used to evaluate effect on regulation
      of BCR-ABL expression, inhibition of cell proliferation and tumour formation in
      vivo in human and murine BCR-ABL expressing cell lines. Tyrphostin AG1024 was
      shown to downregulate expression of BCR-ABL and P-Akt, and to upregulate DNA-PKcs
      expression. In addition, Tyrphostin AG1024 was able to inhibit cell
      proliferation, and delay tumour growth in vivo. Thus, AG1024 is able to interfere
      with three major targets of BCR-ABL in leukaemic cells. Interestingly, Tyrphostin
      AG1024 was also effective against cells resistant to STI571 by distinct
      mechanisms including Bcr-Abl mutation. Therefore, these data suggest that
      Tyrphostin AG1024 could represent the basis of a novel therapy for STI571
      refractory CML.

PMID- 15494719
TI  - Multiple roles of mucins in pancreatic cancer, a lethal and challenging
      malignancy.
AB  - Mucins are members of an expanding family of large multifunctional glycoproteins.
      Pancreatic mucins have important biological functions, including the protection,
      lubrication, and moisturisation of the surfaces of epithelial tissues lining
      ductal structures within the pancreas. Several lines of evidence support the
      notion that deregulated mucin production is a hallmark of inflammatory and
      neoplastic disorders of the pancreas. Herein, we discuss the factors that
      contribute to the lethality of pancreatic cancer as well as the key role played
      by mucins, particularly MUC1 and MUC4, in the development and progression of the
      disease. Aspects pertaining to the aberrant expression and glycosylation of
      mucins are discussed, with special emphasis on their potential impact on the
      design and implementation of adequate diagnostic and therapeutic strategies for
      combating this lethal malignancy.

PMID- 15494720
TI  - Mutant, wild type, or overall p53 expression: freedom from clinical progression
      in tumours of astrocytic lineage.
AB  - Abnormalities of the p53 tumor-suppressor gene are found in a significant
      proportion of astrocytic brain tumours. We studied tumour specimens from 74
      patients evaluated over 20 years at the Massachusetts General Hospital, where
      clinical outcome could be determined and sufficient pathologic material was
      available for immunostaining. p53 expression studies employed an affinity
      purified p53 monoclonal antibody, whose specificity was verified in absorption
      studies and, in a minority of cases, a second antibody recognising a different
      epitope of p53. Significant overexpression of p53 protein was found in 48% of the
      74 tumours included in this series and high levels of expression were associated
      with higher mortality from astrocytic tumours (P<0.001, log rank). Multivariate
      analyses revealed that immunohistochemically detected p53 was an independent
      marker of shortened progression-free and overall actuarial survival in patients
      with astrocytic tumours, suggesting that increased expression of p53 plays an
      important role in the pathobiology of these tumours. In a subset of 36 cases,
      coding regions of the p53 gene were completely sequenced via SSCP and direct DNA
      sequencing, revealing that overexpression of p53 protein is not always associated
      with point mutations in conserved exons of the p53 gene. Finally, we confirmed
      p53 protein expression in early-passage human glioma cell lines of known p53
      mutational status and immunostaining scores. Although grade continues to be the
      strongest prognostic variable, the use of p53 staining as a prognostic indicator,
      in contrast to mutational DNA analyses, may be a useful adjunct in identifying
      patients at higher risk of treatment failure.

PMID- 15494721
TI  - Combination of pegylated liposomal doxorubicin (PLD) and paclitaxel in patients
      with advanced soft tissue sarcoma: a phase II study of the Hellenic Cooperative
      Oncology Group.
AB  - Patients with soft tissue sarcoma (STS), even after complete local disease
      control, often relapse locally or with distant metastases. This multicenter phase
      II study was conducted to evaluate the safety and efficacy of the combination of
      pegylated liposomal doxorubicin (PLD) and paclitaxel, as first-line treatment in
      patients with advanced STS. In all, 42 patients with locally advanced or
      metastatic STS, median age 54 years and median Eastern Cooperative Oncology Group
      performance status (PS) 1 were treated with PLD 45 mg m(-2) and paclitaxel 150 mg
      m(-2), every 28 days for a total of six cycles. Histological types included
      mainly leiomyosarcomas (43%), malignant fibrous histiocytomas (14%) and
      liposarcomas (12%). At study entry, 69% of patients had distant metastases.
      Overall response rate was 16%, including one complete (CR 2%) and six partial
      responses (PRs 14%), while an additional 14 patients had disease stabilization
      (SD 33%). At median follow-up 41.5 months, median time to progression (TTP) was
      5.7 months with median overall survival (OS) 13.2 months. Grade 3-4 toxicities
      included neutropenia (17%), anaemia (15%), neurotoxicity (5%) and palmar-plantar
      erythrodysesthesia (9%). There were no treatment-related deaths. The combination
      of PLD and paclitaxel is a safe and well-tolerated regimen demonstrating modest
      efficacy as first-line treatment in patients with advanced STS.

PMID- 15494722
TI  - Expression of FAP-1 by human colon adenocarcinoma: implication for resistance
      against Fas-mediated apoptosis in cancer.
AB  - Although colon carcinoma cells express Fas receptors, they are resistant to Fas
      mediated apoptosis. Defects within the intracellular Fas signal transduction may
      be responsible. We investigated whether the Fas-associated phosphatase-1 (FAP-1),
      an inhibitor of Fas signal transduction, contributed to this resistance in colon
      carcinomas. In vivo, apoptosis of cancer cells was detected in situ using
      terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling (TUNEL).
      FAP-1, FasR, and Fas ligand (FasL) were detected using immunohistochemistry. In
      vitro, colon carcinoma cells were primarily cultured, and their sensitivity to
      Fas-mediated apoptosis was evaluated by treatment with agonistic anti-FasR CH11
      IgM monoclonal antibody in the presence or absence of synthetic Ac-SLV (serine
      leucine-valine) tripeptide. Fas-associated phosphatase-1 expression was detected
      in 20 out of 28 colon adenocarcinomas. In vivo, a positive correlation between
      the percentage of apoptotic tumour cells and the number of FasL-positive tumour
      infiltrating lymphocytes was observed in FAP-1 negative cancers, but not in FAP-1
      positive ones. Primarily cultured colon cancer cells, which were refractory to CH
      11-induced apoptosis, had higher expression of FAP-1 on protein and mRNA levels
      than the sensitive group. Resistance to Fas-mediated apoptosis in tumour cells
      could be abolished by Ac-SLV tripetides. Fas-associated phosphatase-1 expression
      protects colon cancer cells from Fas-mediated apoptosis, and blockade of FAP-1
      and FasR interaction sensitises tumour cells to Fas-dependent apoptosis.

PMID- 15494723
TI  - Fhit-deficient normal and cancer cells are mitomycin C and UVC resistant.
AB  - To identify functions of the fragile tumour suppressor gene, FHIT, matched pairs
      of Fhit-negative and -positive human cancer cell clones, and normal cell lines
      established from Fhit -/- and +/+ mice, were stressed and examined for
      differences in cell cycle kinetics and survival. A larger fraction of Fhit
      negative human cancer cells and murine kidney cells survived treatment with
      mitomycin C or UVC light compared to matched Fhit-positive cells; approximately
      10-fold more colonies of Fhit-deficient cells survived high UVC doses in
      clonigenic assays. The human cancer cells were synchronised in G1, released into
      S and treated with UVC or mitomycin C. At 18 h post mitomycin C treatment
      approximately 6-fold more Fhit-positive than -negative cells had died, and 18 h
      post UVC treatment 3.5-fold more Fhit-positive cells were dead. Similar results
      were obtained for the murine -/- cells. After low UVC doses, the rate of DNA
      synthesis in -/- cells decreased more rapidly and steeply than in +/+ cells,
      although the Atr-Chk1 pathway appeared intact in both cell types. UVC surviving
      Fhit -/- cells appear transformed and exhibit >5-fold increased mutation
      frequency. This increased mutation burden could explain the susceptibility of
      Fhit-deficient cells in vivo to malignant transformation.

PMID- 15494726
TI  - Activity-dependent transcription regulation of PSD-95 by neuregulin-1 and Eos.
AB  - Neuregulin-1 (Nrg-1) contains an intracellular domain (Nrg-ICD) that translocates
      into the nucleus, where it may regulate gene expression upon neuronal
      depolarization. However, the identity of its target promoters and the mechanisms
      by which it regulates transcription have been elusive. Here we report that, in
      the mouse cochlea, synaptic activity increases the level of nuclear Nrg-ICD and
      upregulates postsynaptic density protein-95 (PSD-95), a scaffolding protein that
      is enriched in post-synaptic structures. Nrg-ICD enhances the transcriptional
      activity of the PSD-95 promoter by binding to a zinc-finger transcription factor,
      Eos. The Nrg-ICD-Eos complex induces endogenous PSD-95 expression in vivo through
      a signaling pathway that is mostly independent of gamma-secretase regulation.
      This upregulation of PSD-95 expression by the Nrg-ICD-Eos complex provides a
      molecular basis for activity-dependent synaptic plasticity.

PMID- 15494727
TI  - Distant influences of amygdala lesion on visual cortical activation during
      emotional face processing.
AB  - Emotional visual stimuli evoke enhanced responses in the visual cortex. To test
      whether this reflects modulatory influences from the amygdala on sensory
      processing, we used event-related functional magnetic resonance imaging (fMRI) in
      human patients with medial temporal lobe sclerosis. Twenty-six patients with
      lesions in the amygdala, the hippocampus or both, plus 13 matched healthy
      controls, were shown pictures of fearful or neutral faces in task-releant or task
      irrelevant positions on the display. All subjects showed increased fusiform
      cortex activation when the faces were in task-relevant positions. Both healthy
      individuals and those with hippocampal damage showed increased activation in the
      fusiform and occipital cortex when they were shown fearful faces, but this was
      not the case for individuals with damage to the amygdala, even though visual
      areas were structurally intact. The distant influence of the amygdala was also
      evidenced by the parametric relationship between amygdala damage and the level of
      emotional activation in the fusiform cortex. Our data show that combining the
      fMRI and lesion approaches can help reveal the source of functional modulatory
      influences between distant but interconnected brain regions.

PMID- 15494728
TI  - GFAP-expressing progenitors are the principal source of constitutive neurogenesis
      in adult mouse forebrain.
AB  - Establishing the cellular identity in vivo of adult multipotent neural
      progenitors is fundamental to understanding their biology. We used two transgenic
      strategies to determine the relative contribution of glial fibrillary acidic
      protein (GFAP)-expressing progenitors to constitutive neurogenesis in the adult
      forebrain. Transgenically targeted ablation of dividing GFAP-expressing cells in
      the adult mouse subependymal and subgranular zones stopped the generation of
      immunohistochemically identified neuroblasts and new neurons in the olfactory
      bulb and the hippocampal dentate gyrus. Transgenically targeted cell fate mapping
      showed that essentially all neuroblasts and neurons newly generated in the adult
      mouse forebrain in vivo, and in adult multipotent neurospheres in vitro, derived
      from progenitors that expressed GFAP. Constitutively dividing GFAP-expressing
      progenitors showed predominantly bipolar or unipolar morphologies with
      significantly fewer processes than non-neurogenic multipolar astrocytes. These
      findings identify morphologically distinctive GFAP-expressing progenitor cells as
      the predominant sources of constitutive adult neurogenesis, and provide new
      methods for manipulating and investigating these cells.

PMID- 15494729
TI  - Interactions between decision making and performance monitoring within prefrontal
      cortex.
AB  - Our ability to judge the consequences of our actions is central to rational
      decision making. A large body of evidence implicates primate prefrontal regions
      in the regulation of this ability. It has proven extremely difficult, however, to
      separate functional areas in the frontal lobes. Using functional magnetic
      resonance imaging, we demonstrate complementary and reciprocal roles for the
      human orbitofrontal (OFC) and dorsal anterior cingulate cortices (ACd) in
      monitoring the outcome of behavior. Activation levels in these regions were
      negatively correlated, with activation increasing in the ACd and decreasing in
      the OFC when the selected response was the result of the participant's own
      decision. The pattern was reversed when the selected response was guided by the
      experimenter rather than the participant. These results indicate that the neural
      mechanisms underlying the way we assess the consequences of choices differ
      depending on whether we are told what to do or are able to exercise our volition.

PMID- 15494730
TI  - Hedgehog signaling from the ZLI regulates diencephalic regional identity.
AB  - The zona limitans intrathalamica (ZLI), a narrow compartment in the vertebrate
      forebrain that bisects the diencephalon transversely, expresses the secreted
      factor sonic hedgehog (Shh). Because genetic disruption of Shh in mouse causes
      severe early developmental defects, this strategy has not been useful in
      identifying a ZLI-specific role for this gene. To modulate Shh signaling in a
      spatiotemporally restricted manner, we carried out gain- and loss-of-function
      experiments in chick embryos using in ovo electroporation and found that Shh
      signaling is required for region-specific gene expression in thalamus and
      prethalamus, the major diencephalic brain areas flanking the ZLI. We further show
      that differential competence of thalamic and prethalamic primordia in responding
      to Shh signaling is regulated by the transcription factor Irx3. We show that,
      through the release of Shh, the ZLI functions as a local signaling center that
      regulates the acquisition of identity for these important diencephalic regions.

PMID- 15494731
TI  - A de novo mutation affecting human TrkB associated with severe obesity and
      developmental delay.
AB  - An 8-year-old male with a complex developmental syndrome and severe obesity was
      heterozygous for a de novo missense mutation resulting in a Y722C substitution in
      the neurotrophin receptor TrkB. This mutation markedly impaired receptor
      autophosphorylation and signaling to MAP kinase. Mutation of NTRK2, which encodes
      TrkB, seems to result in a unique human syndrome of hyperphagic obesity. The
      associated impairment in memory, learning and nociception seen in the proband
      reflects the crucial role of TrkB in the human nervous system.

PMID- 15494732
TI  - Netrin requires focal adhesion kinase and Src family kinases for axon outgrowth
      and attraction.
AB  - Although netrins are an important family of neuronal guidance proteins,
      intracellular mechanisms that mediate netrin function are not well understood.
      Here we show that netrin-1 induces tyrosine phosphorylation of proteins including
      focal adhesion kinase (FAK) and the Src family kinase Fyn. Blockers of Src family
      kinases inhibited FAK phosphorylation and axon outgrowth and attraction by
      netrin. Dominant-negative FAK and Fyn mutants inhibited the attractive turning
      response to netrin. Axon outgrowth and attraction induced by netrin-1 were
      significantly reduced in neurons lacking the FAK gene. Our results show the
      biochemical and functional links between netrin, a prototypical neuronal guidance
      cue, and FAK, a central player in intracellular signaling that is crucial for
      cell migration.

PMID- 15494733
TI  - Focal adhesion kinase in netrin-1 signaling.
AB  - Netrins are a family of secreted molecules that are important for axonal
      outgrowth and guidance in the developing nervous system. However, the signaling
      mechanisms that lie immediately downstream of netrin receptors remain poorly
      understood. Here we report that the netrin receptor DCC (deleted in colorectal
      cancer) interacts with the focal adhesion kinase (FAK), a kinase implicated in
      regulating cell adhesion and migration. FAK was expressed in developing brains
      and was localized with DCC in cultured neurons. Netrin-1 induced FAK and DCC
      tyrosine phosphorylation. Disruption of FAK signaling abolished netrin-1-induced
      neurite outgrowth and attractive growth cone turning. Taken together, these
      results indicate a new signaling mechanism for DCC, in which FAK is activated
      upon netrin-1 stimulation and mediates netrin-1 function; they also identify a
      critical role for FAK in axon navigation.

PMID- 15494735
TI  - Healthy Eating Index and C-reactive protein concentration: findings from the
      National Health and Nutrition Examination Survey III, 1988-1994.
AB  - OBJECTIVE: To examine whether diet quality is associated with C-reactive protein
      concentration. DESIGN: Cross-sectional study using data from the Third National
      Health and Nutrition Examination Survey (1988-1994). SETTING: Representative
      sample of the US population. SUBJECTS: A total of 13 811 men and women aged >/=20
      y. INTERVENTIONS: We examined the cross-sectional associations between the
      Healthy Eating Index (HEI), a measure of diet quality according to the Dietary
      Guidelines for Americans, and serum C-reactive protein concentration. Dietary
      information was assessed using a 24-h recall. RESULTS: After adjustment for age,
      sex, race or ethnicity, education, smoking status, cotinine concentration, body
      mass index, waist-hip-ratio, aspirin use, alcohol use, physical activity level,
      and energy intake, HEI score was inversely associated with an elevated C-reactive
      protein concentration in logistic regression analysis (odds ratio per 10 unit
      change: 0.92; 95th confidence interval (CI): 0.86-0.99). Among the components,
      only the score for grain consumption was inversely associated with an elevated C
      reactive protein concentration. Compared with participants in the lowest quintile
      of number of servings of grain consumption, the adjusted odds ratios of having an
      elevated C-reactive protein concentration for participants in the second, third,
      fourth, and fifth quintiles were 0.87 (95th CI: 0.67, 1.12), 0.85 (95th CI: 0.69,
      1.06), 0.79 (95th CI: 0.65, 0.96), and 0.68 (95th CI: 0.52, 0.88), respectively.
      CONCLUSIONS: Grain consumption may reduce inflammation. Our findings require
      confirmation.

PMID- 15494734
TI  - Activation of FAK and Src are receptor-proximal events required for netrin
      signaling.
AB  - The axon guidance cue netrin is importantly involved in neuronal development. DCC
      (deleted in colorectal cancer) is a functional receptor for netrin and mediates
      axon outgrowth and the steering response. Here we show that different regions of
      the intracellular domain of DCC directly interacted with the tyrosine kinases Src
      and focal adhesion kinase (FAK). Netrin activated both FAK and Src and stimulated
      tyrosine phosphorylation of DCC. Inhibition of Src family kinases reduced DCC
      tyrosine phosphorylation and blocked both axon attraction and outgrowth of
      neurons in response to netrin. Mutation of the tyrosine phosphorylation residue
      in DCC abolished its function of mediating netrin-induced axon attraction. On the
      basis of our observations, we suggest a model in which DCC functions as a kinase
      coupled receptor, and FAK and Src act immediately downstream of DCC in netrin
      signaling.

PMID- 15494736
TI  - Lower resting metabolic rate in the elderly may not be entirely due to changes in
      body composition.
AB  - OBJECTIVE: To investigate whether or not the lower resting metabolic rate (RMR)
      in the elderly is entirely due to changes in body composition. DESIGN: Cross
      sectional data of 132 female (age 69.9+/-5.5 y, body mass index (BMI) 26.5+/-4.0
      kg/m(2)) and 84 male (age 68.9+/-5.1 y, BMI 26.1+/-2.8 kg/m(2)) participants of
      the longitudinal study on nutrition and health status in an aging population of
      Giessen, Germany, as well as that of 159 young women (age 24.8+/-3.0 y, BMI
      21.1+/-2.5 kg/m(2)) and 67 young men (age 26.8+/-3.4 y, BMI 23.3+/-2.4 kg/m(2))
      were analysed. RMR was measured by indirect calorimetry after an overnight fast
      and body composition was estimated by bioelectrical impedance analysis and
      predictive equations from the literature. Analysis of covariance was used to
      adjust RMR for body composition, body fat distribution and smoking habits.
      Additionally, RMR that is to be expected theoretically, was calculated on the
      basis of the subjects' body composition and the specific metabolic rate of the
      different organs and was compared to measured RMR. RESULTS: Compared to young
      subjects adjusted RMR was significantly lower in elderly women (5432+/-82 vs
      5809+/-70 kJ/day, P<0.01) and men (6971+/-99 vs 7558+/-121 kJ/day, P<0.001). In
      both elderly women and men, measured RMR was markedly lower than calculated RMR (
      625+/-404, -515+/-570 kJ/day). By contrast, measured and calculated RMR were
      nearly the same in young men (159+/-612 kJ/day); in young women the difference
      between measured and calculated RMR was only -300+/-457 kJ/day. In both sexes,
      these differences are significantly larger in the elderly when compared to young
      adults. CONCLUSION: These results support the point of view that the decline in
      RMR with advancing age cannot be totally due to changes in body composition.

PMID- 15494737
TI  - Screening for FXTAS.

PMID- 15494738
TI  - Genome-wide screening using array-CGH does not reveal
      microdeletions/microduplications in children with Kabuki syndrome.
AB  - Kabuki syndrome (KS) is a rare multiple congenital anomaly/mental retardation
      syndrome. It is characterized by a distinct facial appearance, mental
      retardation, postnatal growth retardation, skeletal anomalies, unusual
      dermatoglyphics and fetal fingertip pads. It has previously been speculated that
      KS is caused by a microdeletion or duplication. In a recent report, an
      interstitial microduplication of 8p22-23.1 was presented in several cases with
      this disorder. We investigated 10 Caucasian patients diagnosed with KS by
      fluorescence in situ hybridization and microsatellite markers located on 8p22
      23.1. Using the same clones that were previously reported to be duplicated on
      chromosome 8p, we could exclude the duplication in all our patients. In addition,
      we performed a genome-wide screening on this group of patients using array-based
      comparative genomic hybridization containing BAC clones spaced at approximately 1
      Mb intervals across the genome and could not find any evidence for gene dose
      alterations. The characteristics of KS are variable, a fact that complicates the
      diagnosis of this disorder. It is possible that we will find genetic
      heterogeneity among Kabuki patients, and therefore it is unlikely that all
      patients have an interstitial 8p duplication. We conclude that the etiology of KS
      remains to be solved and further genetic studies are necessary to delineate its
      genetic cause.

PMID- 15494739
TI  - No association between three xeroderma pigmentosum group C and one group G gene
      polymorphisms and risk of cutaneous melanoma.
AB  - Xeroderma pigmentosum (XP) patients exhibit a 1000-fold increased risk for
      developing skin cancers including malignant melanoma. We investigated the role of
      three variant alleles of the DNA repair gene XPC and one variant allele of the
      XPG gene in a hospital-based case-control study of 294 Caucasian patients from
      Germany with malignant melanoma and 375 healthy control individuals from the same
      area matched by sex. The polymorphisms G1580A (XPC exon 8; Arg492His), T1601C
      (XPC exon 8; Val499Ala), G2166A (XPC exon 10; Arg687Arg), and C3507G (XPG exon
      15; Asp1104His) were not in linkage disequilibrium. The allele frequencies
      (cases: controls) were for 1580A 6.29%: 5.63%, for 1601C 79.08%: 78.28%, for
      2166A 26.19%: 28.13%, and for 3507G 79.86%: 78.61%. We found no association of
      the homozygous 1580A, 1601C, 2166A, and 3507G genotypes with increased risks of
      melanoma: OR 1.254 (95% CI: 0.486-3.217), OR 1.108 (95% CI: 0.629-1.960), OR
      0.817 (95% CI: 0.490-1.358), and OR 1.168 (95% CI: 0.670-2.044), respectively.
      Exploratory analyses of subgroups of melanoma patients compared to all controls
      indicated no association of these genotypes with increased risks for development
      of multiple primary melanomas (n = 28), a negative family history for melanoma (n
      = 277), melanomas in individuals with a low number of nevi (n = 273), melanomas
      in individuals older than 55 years (n = 142), and melanomas thicker than 1 mm (n
      = 126).

PMID- 15494740
TI  - Association of haplotypes in the beta-chemokine locus with multiple sclerosis.
AB  - Linkage studies in multiple sclerosis (MS) identified several susceptibility
      loci. One of these regions includes chromosome 17q11 where a meta-analysis of
      data from three genome scans suggested linkage. This region encodes a cluster of
      genes for beta-chemokines or CC chemokine ligands (CCLs), which may be involved
      in the development of MS lesions. Here we aimed to test if CCL alleles and
      haplotypes are associated with MS. Using methods of linkage and association, we
      observed deviations from the expected 50% transmission of haplotypes from
      unaffected parents to their affected children at CCL2, CCL11-CCL8-CCL13 and CCL3
      within the investigated 1.85 MB chromosomal segment. Analyses of the linkage
      disequilibrium map support that variants with possible relevance to MS can be
      located within these subregions. Identification of MS associated CCL variants may
      have direct clinical significance, as it can lead to the design of small
      competitive antagonists of these molecules with beneficial effects in the
      treatment of patients with early and active disease.

PMID- 15494741
TI  - Single-nucleotide polymorphisms in genes relating to homocysteine metabolism: how
      applicable are public SNP databases to a typical European population?
AB  - To facilitate the association studies in complex diseases characterized by
      hyperhomocysteinemia, we collected structural and frequency data on single
      nucleotide polymorphism (SNPs) in 24 genes relating to homocysteine metabolism.
      Firstly, we scanned approximately 1.2 Mbp of sequence in the NCBI SNP database
      (dbSNP) build 110 and we detected 1353 putative SNPs with an average in silico
      genic density of 1:683. Out of 112 putative SNPs in coding regions (cSNPs), we
      selected a subset of 42 cSNPs and we assessed the applicability of the NCBI dbSNP
      to the Czech population - a typical representative of European Caucasians - by
      determining the frequency of the putative cSNPs experimentally by PCR-RFLP or
      ARMS-PCR in at least 110 control Czech chromosomes. As only 25 of the 42 analyzed
      cSNPs met the criterion of >/=1% frequency, the positive predictive value of the
      NCBI data set for our population reached 60%, which is similar to other studies.
      The correlation of SNP frequency between Czechs and other Caucasians - obtained
      from NCBI and/or literature - was stronger (r(2)=0.90 for 20 cSNPs) than between
      Czechs and general NCBI database entries (r(2)=0.73 for 27 cSNPs). Moreover,
      frequencies of all 20 putative cSNPs, for which data in Caucasians were
      available, were congruently below or above the 1% frequency criterion both in
      Czechs and in other Caucasians. In summary, our study shows that the NCBI dbSNP
      is a useful tool for selecting cSNPs for genetic studies of hyperhomocysteinemia
      in European populations, although experimental validation of SNPs should be
      performed, especially if the cSNP entry lacks any frequency data in Caucasians.

PMID- 15494742
TI  - Microarray-based mutation analysis of the ABCA4 (ABCR) gene in autosomal
      recessive cone-rod dystrophy and retinitis pigmentosa.
AB  - Mutations in the ABCA4 gene have been associated with autosomal recessive
      Stargardt disease (STGD1), cone-rod dystrophy (CRD), and retinitis pigmentosa
      (RP). We employed a recently developed genotyping microarray, the ABCR400-chip,
      to search for known ABCA4 mutations in patients with isolated or autosomal
      recessive CRD (54 cases) or RP (90 cases). We performed detailed ophthalmologic
      examinations and identified at least one ABCA4 mutation in 18 patients (33%) with
      CRD and in five patients (5.6%) with RP. Single-strand conformation polymorphism
      (SSCP) analysis and subsequent DNA sequencing revealed four novel missense
      mutations (R24C, E161K, P597S, G618E) and a novel 1-bp deletion (5888delG).
      Ophthalmoscopic abnormalities in CRD patients ranged from minor granular
      pigmentary changes in the posterior pole to widespread atrophy. In 12 patients
      with recordable electroretinogram (ERG) tracings, a cone-rod pattern was
      detected. Three patients demonstrated progression from a retinal dystrophy
      resembling STGD1 to a more widespread degeneration, and were subsequently
      diagnosed as CRD. In addition to a variable degree of atrophy, all RP patients
      displayed ophthalmologic characteristics of classic RP. When detectable, ERG
      recordings in these patients demonstrated rod-cone patterns of photoreceptor
      degeneration. In conclusion, in this study, we show that the ABCA4 mutation chip
      is an efficient first screening tool for arCRD.

PMID- 15494743
TI  - The state of the prion.
AB  - There is little doubt that the main component of the transmissible agent of
      spongiform encephalopathies - the prion - is a conformational variant of the
      ubiquitous host protein PrP(C), and that the differing properties of various
      prion strains are associated with different abnormal conformations of this
      protein. The precise structure of the prion is not yet known, nor are the
      mechanisms of infection, conformational conversion and pathogenesis understood.

PMID- 15494744
TI  - Comparative analysis of four Campylobacterales.
AB  - Comparative genome analysis can be used to identify species-specific genes and
      gene clusters, and analysis of these genes can give an insight into the
      mechanisms involved in a specific bacteria-host interaction. Comparative analysis
      can also provide important information on the genome dynamics and degree of
      recombination in a particular species. This article describes the comparative
      genome analysis of representatives of four different Campylobacterales species -
      two pathogens of humans, Helicobacter pylori and Campylobacter jejuni, as well as
      Helicobacter hepaticus, which is associated with liver cancer in rodents, and the
      non-pathogenic commensal species, Wolinella succinogenes.

PMID- 15494745
TI  - Genome-scale models of microbial cells: evaluating the consequences of
      constraints.
AB  - Microbial cells operate under governing constraints that limit their range of
      possible functions. With the availability of annotated genome sequences, it has
      become possible to reconstruct genome-scale biochemical reaction networks for
      microorganisms. The imposition of governing constraints on a reconstructed
      biochemical network leads to the definition of achievable cellular functions. In
      recent years, a substantial and growing toolbox of computational analysis methods
      has been developed to study the characteristics and capabilities of
      microorganisms using a constraint-based reconstruction and analysis (COBRA)
      approach. This approach provides a biochemically and genetically consistent
      framework for the generation of hypotheses and the testing of functions of
      microbial cells.

PMID- 15494746
TI  - Escherichia coli acid resistance: tales of an amateur acidophile.
AB  - Gastrointestinal pathogens are faced with an extremely acidic environment. Within
      moments, a pathogen such as Escherichia coli O157:H7 can move from the nurturing
      pH 7 environment of a hamburger to the harsh pH 2 milieu of the stomach.
      Surprisingly, certain microorganisms that grow at neutral pH have elegantly
      regulated systems that enable survival during excursions into acidic
      environments. The best-characterized acid-resistance system is found in E. coli.

PMID- 15494747
TI  - Evidence of an absence: the genetic origins of the 1918 pandemic influenza virus.
AB  - Annual outbreaks of influenza A infection are an ongoing public health threat and
      novel influenza strains can periodically emerge to which humans have little
      immunity, resulting in devastating pandemics. The 1918 pandemic killed at least
      40 million people worldwide and pandemics in 1957 and 1968 caused hundreds of
      thousands of deaths. The influenza A virus is capable of enormous genetic
      variation, both by continuous, gradual mutation and by reassortment of genome
      segments between viruses. Both the 1957 and 1968 pandemic strains are thought to
      have originated as reassortants in which one or both human-adapted viral surface
      proteins were replaced by proteins from avian influenza strains. Analyses of the
      genes of the 1918 pandemic virus, however, indicate that this strain might have
      had a different origin. The haemagglutinin and nucleoprotein genome segments in
      particular are unlikely to have come directly from an avian source that is
      similar to those that are currently being sequenced. Determining whether a
      pandemic influenza virus can emerge by different mechanisms will affect the scope
      and focus of surveillance and prevention efforts.

PMID- 15494748
TI  - Scientific R&D: time to revise the rules?
AB  - For several decades scientific R&D has been failing communities around the world,
      especially in developing countries, by not producing an adequate level of
      benefits (for example, improved health and living standards) and essential public
      goods (for example, the provision of safe water, sanitation and energy). It is
      time for a complete overhaul of the R&D process, with a comprehensive review of
      the mechanisms by which R&D is financed, how and where the work and results are
      published and disseminated, how the results and knowledge are exploited, and how
      ownership is decided. This is particularly important for public goods, for which
      there is often no market or prospect of commercial return or profit.

PMID- 15494749
TI  - How long will it last?

PMID- 15494750
TI  - Down with "op. cit.".

PMID- 15494751
TI  - Emphasis on the need for guidelines for documentation of search strategy and
      results was needed, criticism of a Cochrane review was not.

PMID- 15494754
TI  - Impact of an evidence-based medicine curriculum on medical students' attitudes
      and skills.
AB  - PURPOSE: This evaluation study sought to assess the impact of an evidence-based
      medicine (EBM) course on students' self-perception of EBM skills, determine their
      use of EBM skills, and measure their performance in applying EBM skills in a
      simulated case scenario. METHODS: Pre- and post-surveys and skills tests were
      developed to measure students' attitudes toward and proficiency in EBM skills.
      Third-year students completed the voluntary survey and skills test at the
      beginning and completion of a twelve-week clerkship in internal medicine (IM) co
      taught by medical and library faculty. Data were analyzed using the Mann-Whitney
      U test for a two-tailed test. RESULTS: A statistically significant increase was
      found in the students' self-assessment of skills. Students reported using the
      journal literature significantly more frequently during the clerkship than
      before, although textbooks remained their number one resource. A majority of
      students reported frequent use of EBM skills during the clerkship. Statistically
      significant improvement in student performance was also found on the posttest,
      although the level of improvement was more modest than that found on the post
      surveys. CONCLUSION: The introduction of EBM skills to students during a clinical
      clerkship provides students an opportunity to practice EBM skills and reinforces
      the use of evidence in making patient-care decisions.

PMID- 15494755
TI  - Evidence-based databases versus primary medical literature: an in-house
      investigation on their optimal use.
AB  - OBJECTIVE: The objective is to investigate the effectiveness of evidence-based
      medicine (EBM) resources in providing evidence for complex clinical questions
      versus general care management questions to identify situations for their optimal
      use. METHODS: In this investigation, forty complex clinical questions were
      randomly selected from an in-house archival database of questions received by
      librarians during clinical rounds. An additional forty questions were selected
      from a list of general care management questions received by the library from
      Pathways teams. To measure the effectiveness of resources in answering the
      questions, a team of librarians was asked to search UpToDate, the Cochrane
      Database of Systematic Reviews, and HealthGate Clinical Guidelines (formerly, EBM
      Solutions). The team then established consensus on whether a question was fully
      or partially answered by one of the above-mentioned EBM resources and was
      instructed to record the instances in which the primary literature needed to be
      used to answer the question completely. RESULTS: The study found that the EBM
      resources completely answered 20.0% of the 40 complex clinical questions and
      47.5% of the 40 general care management questions, partially answered 40.0% of
      the complex clinical questions and 22.5% of the general care management
      questions, and did not answer 40.0% of the complex clinical questions and 30.0%
      of the general care management questions. CONCLUSION: The pervasive use of EBM
      resources in answering clinical questions is making it imperative for information
      specialists to develop an expertise on their appropriate use. By exploring their
      use in answering complex clinical questions and general care management
      questions, this paper underlines the strengths and weakness of EBM resources and
      provides information specialists with some basic knowledge about how these
      resources can be combined with the primary literature to strengthen their
      effectiveness.

PMID- 15494756
TI  - Academic health sciences library Website navigation: an analysis of forty-one
      Websites and their navigation tools.
AB  - BACKGROUND: The analysis included forty-one academic health sciences library
      (HSL) Websites as captured in the first two weeks of January 2001. Home pages and
      persistent navigational tools (PNTs) were analyzed for layout, technology, and
      links, and other general site metrics were taken. METHODS: Websites were selected
      based on rank in the National Network of Libraries of Medicine, with regional and
      resource libraries given preference on the basis that these libraries are
      recognized as leaders in their regions and would be the most reasonable source of
      standards for best practice. A three-page evaluation tool was developed based on
      previous similar studies. All forty-one sites were evaluated in four specific
      areas: library general information, Website aids and tools, library services, and
      electronic resources. Metrics taken for electronic resources included orientation
      of bibliographic databases alphabetically by title or by subject area and with
      links to specifically named databases. RESULTS: Based on the results, a formula
      for determining obligatory links was developed, listing items that should appear
      on all academic HSL Web home pages and PNTs. CONCLUSIONS: These obligatory links
      demonstrate a series of best practices that may be followed in the design and
      construction of academic HSL Websites.

PMID- 15494757
TI  - Web usage mining at an academic health sciences library: an exploratory study.
AB  - OBJECTIVES: This paper explores the potential of multinomial logistic regression
      analysis to perform Web usage mining for an academic health sciences library
      Website. METHODS: Usage of database-driven resource gateway pages was logged for
      a six-month period, including information about users' network addresses,
      referring uniform resource locators (URLs), and types of resource accessed.
      RESULTS: It was found that referring URL did vary significantly by two factors:
      whether a user was on-campus and what type of resource was accessed. CONCLUSIONS:
      Although the data available for analysis are limited by the nature of the Web and
      concerns for privacy, this method demonstrates the potential for gaining insight
      into Web usage that supplements Web log analysis. It can be used to improve the
      design of static and dynamic Websites today and could be used in the design of
      more advanced Web systems in the future.

PMID- 15494758
TI  - How much effort is needed to keep up with the literature relevant for primary
      care?
AB  - OBJECTIVES: Medicine must keep current with the research literature, and keeping
      current requires continuously updating the clinical knowledge base (i.e.,
      references that provide answers to clinical questions). The authors estimated the
      volume of medical literature potentially relevant to primary care published in a
      month and the time required for physicians trained in medical epidemiology to
      evaluate it for updating a clinical knowledge base. METHODS: We included journals
      listed in five primary care journal review services (ACP Journal Club, DynaMed,
      Evidence-Based Practice, Journal Watch, and QuickScan Reviews). Finding little
      overlap, we added the 2001 "Brandon/Hill Selected List of Print Books and
      Journals for the Small Medical Library." We counted articles (including letters,
      editorials, and other commentaries) published in March 2002, using bibliographic
      software where possible and hand counting when necessary. For journals not
      published in March 2002, we reviewed the nearest issue. Five primary care
      physicians independently evaluated fifty randomly selected articles and timed the
      process. RESULTS: The combined list contained 341 currently active journals with
      8,265 articles. Adjusting for publication frequency, we estimate 7,287 articles
      are published monthly in this set of journals. Physicians trained in epidemiology
      would take an estimated 627.5 hours per month to evaluate these articles.
      CONCLUSIONS: To provide practicing clinicians with the best current evidence,
      more comprehensive and systematic literature surveillance efforts are needed.

PMID- 15494759
TI  - Design and evaluation of a personal digital assistant- based alerting service for
      clinicians.
AB  - PURPOSE: This study describes the system architecture and user acceptance of a
      suite of programs that deliver information about newly updated library resources
      to clinicians' personal digital assistants (PDAs). DESCRIPTION: Participants
      received headlines delivered to their PDAs alerting them to new books, National
      Guideline Clearinghouse guidelines, Cochrane Reviews, and National Institutes of
      Health (NIH) Clinical Alerts, as well as updated content in UpToDate, Harrison's
      Online, Scientific American Medicine, and Clinical Evidence. Participants could
      request additional information for any of the headlines, and the information was
      delivered via e-mail during their next synchronization. Participants completed a
      survey at the conclusion of the study to gauge their opinions about the service.
      RESULTS/OUTCOME: Of the 816 headlines delivered to the 16 study participants'
      PDAs during the project, Scientific American Medicine generated the highest
      proportion of headline requests at 35%. Most users of the PDA Alerts software
      reported that they learned about new medical developments sooner than they
      otherwise would have, and half reported that they learned about developments that
      they would not have heard about at all. While some users liked the PDA platform
      for receiving headlines, it seemed that a Web database that allowed tailored
      searches and alerts could be configured to satisfy both PDA-oriented and e-mail
      oriented users.

PMID- 15494760
TI  - A study of clinical questions posed by hospital clinicians.
AB  - OBJECTIVE: This article presents the results of complementary research studies on
      the behaviors of hospital clinicians in asking clinical questions and the
      relationship between asking of questions, outcome of information searches, and
      success in problem solving. METHODS: Triangulation in research methods--a
      combination of mailed questionnaires, interviews, and a randomized controlled
      study--was employed to provide complementary views of the research problems under
      study. RESULTS: The survey and interviews found that clinical problems (concerned
      mainly with therapy and equipment or technology) were expressed as statements
      rather than questions (average number of concepts = 1.7), that only slightly more
      than half (higher for doctors) of problems could be solved, and that the majority
      of clinical questions were not well formed. An educational workshop however
      improved clinicians' formulation of questions, but the use of structured
      prompting was found to improve building of hypotheses in the doctors' group
      without training. The workshop also improved satisfaction with the obtained
      information and success in problem solving. Nonetheless, for both the
      experimental and control groups, more structured and complete questions or
      statements did not mean higher success rates in problem solving or higher
      satisfaction with obtained information. CONCLUSION: The triangulation methods
      have gathered complementary evidence to reject the hypothesis that building well
      structured clinical questions would mean higher satisfaction with obtained
      information and higher success in problem solving.

PMID- 15494762
TI  - Findings from the most recent Medical Library Association salary survey.
AB  - OBJECTIVE: The objective is to provide information on basic issues in library
      management identified by the Medical Library Association's (MLA's) seventh
      triennial salary survey. METHODS: The survey was a Web-based questionnaire. A
      nonrandom sample of persons was obtained by posting messages to MLA's membership
      and to the MEDLIB-L e-mail discussion list. Employed MLA members and nonmembers
      employed in medical library settings filled out a Web-based form designed using
      common gateway interface (CGI) programming. RESULTS: Six hundred forty-five
      usable responses were analyzed by the Hay Group and presented in the MLA
      publication, Hay Group/MLA 2001 Compensation and Benefits Survey. Results from
      the 2001 survey in this article focus on pay and job satisfaction. Salary survey
      results since 1983 were analyzed to review trends in seniority, diversity, and
      pay equity. CONCLUSIONS: Given the age progression of respondents from 1983 to
      2001, it is clear that succession planning is a core issue for medical libraries.
      Although efforts to create more diversity in medical libraries in member
      organizations have started to yield results, pay for white respondents has
      increased at a higher rate than for other racial categories. The authors found
      that the pay-for-performance system in the organizations of approximately two
      thirds of the respondents is suboptimized and that most of the reasons medical
      librarians cite for leaving their organization can be addressed and potentially
      changed by management. Results from the eighth salary survey, slated to be
      conducted in the fall of 2004, will further track these trends and issues.

PMID- 15494761
TI  - A power information user (PIU) model to promote information integration in
      Tennessee's public health community.
AB  - Observation and immersion in the user community are critical factors in designing
      and implementing informatics solutions; such practices ensure relevant
      interventions and promote user acceptance. Libraries can adapt these strategies
      to developing instruction and outreach. While needs assessment is typically a
      core facet of library instruction, sustained, iterative assessment underlying the
      development of user-centered instruction is key to integrating resource use into
      the workflow. This paper describes the Eskind Biomedical Library's (EBL's) recent
      work with the Tennessee public health community to articulate a training model
      centered around developing power information users (PIUs). PIUs are community
      based individuals with an advanced understanding of information seeking and
      resource use and are committed to championing information integration. As model
      development was informed by observation of PIU workflow and information needs, it
      also allowed for informal testing of the applicability of assessment via domain
      immersion in library outreach. Though the number of PIUs involved in the project
      was small, evaluation indicated that the model was useful for promoting
      information use in PIU workgroups and that the concept of domain immersion was
      relevant to library-related projects. Moreover, EBL continues to employ
      principles of domain understanding inherent in the PIU model to develop further
      interventions for the public health community and library users.

PMID- 15494763
TI  - Veterinary medicine books recommended for academic libraries.
AB  - This bibliography of in-print veterinary medical books published in English may
      be used as an acquisitions or evaluation tool for developing the monograph
      component of new veterinary medicine collections or existing science, technology,
      and medicine collections where veterinary medicine is in the scope of the
      collection. The bibliography is divided into 34 categories and consists of
      bibliographic information for 419 titles. The appendix contains an author/editor
      index. Prices for all entries are in US dollars, except where another currency is
      noted. The total cost of all books in the bibliography is $43,602.13 (US).

PMID- 15494764
TI  - Bioinformatics opportunities for health sciences librarians and information
      professionals.

PMID- 15494765
TI  - The Electronic Fund Transfer System (EFTS).

PMID- 15494766
TI  - Updating hospital reference resources in the United States-associated Pacific
      Basin: efforts of the Pacific Islands Continuing Clinical Education Program
      (PICCEP).

PMID- 15494767
TI  - The role of librarians in patient safety: gaps and strengths in the current
      culture.

PMID- 15494769
TI  - A Google for clinical trials.

PMID- 15494770
TI  - The Canadian Cardiovascular Society and knowledge translation: turning best
      evidence into best practice.
AB  - Care gaps, the discrepancy between processes of care recognized as best practice
      and care provided in usual clinical practice, exist in cardiovascular disease.
      Knowledge translation, the process of turning best evidence into best practices,
      has the potential to reduce care gaps. As the national voice for cardiovascular
      physicians and scientists, the Canadian Cardiovascular Society is committed to
      knowledge translation. The present article describes how knowledge translation
      builds on the constructs of continuing medical education and continuing
      professional development; what can be done to improve knowledge translation; and
      what the Canadian Cardiovascular Society is currently doing about this.

PMID- 15494771
TI  - Should the implantable cardiac defibrillator be used for primary prevention of
      sudden death? A review of the issues relevant to hospital decision making.
AB  - BACKGROUND: New evidence suggests that the implantable cardiac defibrillator
      (ICD) may be effective for primary prevention of sudden death. High instrumental
      cost and the potentially large number of candidates will significantly impact
      hospital budgets. OBJECTIVE: To review the information relevant to hospital
      policy decisions on the use of ICDs for primary prevention. METHODS: Modelling
      based on an evaluation of reported studies and Canadian costs, detailed in a
      comprehensive review available at <http://upload.mcgill.ca/tau/icd.pdf>. RESULTS:
      Health outcomes: Two high-quality primary prevention trials suggest a reduction
      in annual mortality of 2.9% with bounds of probability (PB) of 2.0% to 3.8%, in
      early years. To undertake 100 implants per year may result in an increasing
      annual saving of life-years of acceptable quality, stabilizing by 15 years at 110
      (PB 72 to 154) each year. Economic impact: The annual costs would stabilize at 15
      years at approximately 4.3 million dollars. Cost-effectiveness: The incremental
      cost-effectiveness from the point of view of the health care system would be
      approximately 47,000 dollars (PB 35,000 dollars to 70,000 dollars), discounted at
      3%. Ethical and legal issues: The decision should not be individual but
      institutional, using a process that is transparent, consistent and fair.
      CONCLUSIONS: The ICD can prolong life, with acceptable quality. Restriction of
      its use would be solely on grounds of expense.

PMID- 15494772
TI  - Multidisciplinary outpatient congestive heart failure clinic: impact on hospital
      admissions and emergency room visits.
AB  - BACKGROUND: Life-saving drugs, such as angiotensin-converting enzyme inhibitors
      and beta-blockers, are frequently underused and underdosed in patients with heart
      failure. Specialized clinics have been shown to provide additional benefits.
      OBJECTIVES: To determine the impact of a multidisciplinary outpatient heart
      failure clinic on the frequency of cardiovascular readmissions and emergency room
      (ER) visits, length of inpatient and ER stays, and New York Heart Association
      (NYHA) class. METHODS: A retrospective chart review study comprising 72 patients
      who had two or more visits to a heart failure clinic between December 1, 1998,
      and August 31, 1999, was performed. The number of readmissions and ER visits, and
      the NYHA class were recorded during the six-month period before and after the
      first visit to the clinic. RESULTS: Most subjects were in NYHA class III or IV
      (71% and 21%, respectively), and the mean ejection fraction was 31%. The post-
      versus preintervention relative risk of readmission was 0.43 (95% CI 0.25 to
      0.72). The total number of inpatient days decreased by 54% (95% CI 44% to 62%).
      The post- versus preintervention relative risk of an ER visit was 0.29 (95% CI
      0.19 to 0.45). The number of ER days decreased by 60% (95% CI 41% to 73%). NYHA
      functional class significantly improved, with most subjects ending the six-month
      postintervention period in class I or II (33% and 49%, respectively; P=0.001).
      CONCLUSIONS: This multidisciplinary heart failure clinic significantly decreased
      the risk of cardiovascular readmissions and subsequent ER visits. It led to
      improvement in NYHA class and to a decrease in the number of days spent in the
      hospital and in the ER.

PMID- 15494773
TI  - Troponin I and T levels in renal failure patients without acute coronary
      syndrome: a systematic review of the literature.
AB  - BACKGROUND: Debate surrounds the interpretation of troponin assays for the
      diagnosis and prognosis of cardiac disease in patients with renal failure.
      OBJECTIVES: To systematically review the diagnostic and prognostic test
      characteristics of quantitative serum cardiac troponin I (cTnI) and T (cTnT) in
      renal failure patients without acute coronary syndrome (ACS) symptoms. METHODS:
      English-language literature was identified through searching MEDLINE from 1966 to
      August 2003 and reviewing reference lists. Studies were excluded if they did not
      meet research objectives, had fewer than 10 patients or focused primarily on
      nonrenal patients. Of 119 potential studies, 39 articles with over 349 patients
      with chronic kidney disease (CKD) and 3899 hemodialysis patients were selected
      for abstraction. RESULTS: Among CKD and hemodialysis patients without ACS
      symptoms, cTnI had a mean specificity of 97% (95% CI 93% to 99%) and 96% (95% CI
      94% to 98%), respectively, using the myocardial infarction cut-off threshold. The
      mean specificity of cTnT compared less favourably at 85% (95% CI 75% to 93%) and
      71% (95% CI 64% to 77%) for CKD and hemodialysis patients, respectively. In
      hemodialysis patients without ACS symptoms, positive and negative likelihood
      ratios for all-cause mortality over 12 to 24 months for cTnT were 4.5 (95% CI 2.9
      to 7.1) and 0.6 (95% CI 0.4 to 0.8), and for cTnI were 1.6 (95% CI 0.9 to 2.9)
      and 1.0 (95% CI 0.9 to 1.1), respectively. CONCLUSIONS: In CKD and hemodialysis
      patients without ACS symptoms, troponin I, at the myocardial infarction cut-off
      threshold, is unlikely to be falsely elevated. Among hemodialysis patients
      without ACS symptoms, a positive troponin T helps predict all-cause mortality.

PMID- 15494774
TI  - Influence of education and income on atherogenic risk factor profiles among
      patients hospitalized with acute myocardial infarction.
AB  - BACKGROUND: Survival after acute myocardial infarction (AMI) varies with
      socioeconomic status. It is unknown whether these differences can be attributed,
      in part, to variations in the prevalence of atherogenic risk factors preceding
      the index AMI event. OBJECTIVES: To examine how cardiovascular risk factors
      varied according to person-level indicators of income and education among a
      cohort of younger patients (younger than 65 years of age) hospitalized with AMI
      in Ontario. METHODS: The Socio-Economic and Acute Myocardial Infarction study
      (SESAMI) prospectively assembled a cohort of 3335 patients hospitalized with AMI
      who consented to participate (75% consent rate) from 53 of 57 large-volume
      institutions (100 AMI cases per year or more) throughout Ontario between December
      1, 1999, and June 1, 2002. Given the known challenges inherent in characterizing
      the socioeconomic status in elderly patients and the ubiquity of atherosclerosis
      in elderly persons, the study focused on 1635 nonelderly participants. The
      relationship between income or education and cardiovascular risk factors, after
      adjustment for age, sex, ethnoracial factors and geography (urban-rural status)
      was examined. RESULTS: The prevalence of diabetes, hypertension, smoking and pre
      existing heart disease was higher among poorer, less educated patients, as were
      the total number of cardiovascular risk factors. After adjusting for baseline
      factors, both income (adjusted OR 0.50, 95% CI 0.31 to 0.82, P=0.006) and
      education (adjusted OR 0.52, 95% CI 0.31 to 0.87, P=0.01) were independently
      associated with cardiovascular risk factors or pre-existing heart disease. There
      were no significant interactions between income, education and baseline
      cardiovascular risk. CONCLUSIONS: Outcome differences across socioeconomic strata
      following AMI may reflect major income- and education-related differences in
      atherogenic risk profile.

PMID- 15494775
TI  - Endothelial nitric oxide synthase and methylenetetrahydrofolate reductase gene
      polymorphisms are associated with endothelial dysfunction in young, healthy men.
AB  - BACKGROUND: The guanine to thymine polymorphism at position 894 of the eNOS gene
      (resulting in a change from glutamate to aspartate [Asp] at codon 298 [Asp298])
      and the methylenetetrahydrofolate reductase (MTHFR) gene polymorphism (C677T)
      have been reported to be associated with atherosclerosis and cardiovascular
      disease. Endothelial dysfunction is considered to be the earliest stage of
      atherosclerosis. OBJECTIVES: To examine whether common eNOS and MTHFR gene
      polymorphisms are associated with endothelial dysfunction in young, healthy men
      without overt cardiovascular disease. SUBJECTS AND METHODS: Flow-mediated,
      endothelium-dependent vasodilation (FMD) and glyceryl trinitrate-induced,
      endothelium-independent vasodilation (GTN) were measured using high-resolution
      ultrasound of the brachial artery in 53 young, healthy men assigned to eNOS and
      MTHFR genotypes. RESULTS: Subjects with the eNOS Asp298 allele (n=15) showed
      significantly reduced FMD:GTN compared with those without this allele (n=38)
      (0.23+/-0.13 [mean +/- SD] versus 0.35+/-0.14, P=0.0072), whereas there was no
      significant difference in GTN between these two groups. Although subjects with
      the MTHFR T677 allele did not show significantly reduced levels of FMD:GTN,
      subjects with the eNOS Asp298 allele and who were carriers of the MTHFR T677
      allele demonstrated markedly reduced levels of FMD:GTN compared with noncarriers
      (0.14+/-0.05 versus 0.28+/-0.13, P=0.04). CONCLUSIONS: The data suggest that even
      in young men, the eNOS Asp298 allele may be involved in endothelial dysfunction
      before any overt vascular disease has occurred. Furthermore, a combination of the
      eNOS Asp298 and MTHFR T677 alleles may exaggerate endothelial dysfunction and may
      contribute to a comparatively earlier development of atherosclerosis.

PMID- 15494776
TI  - Real-time dobutamine stress myocardial contrast echocardiography for detecting
      coronary artery disease: correlating abnormal wall motion and disturbed
      perfusion.
AB  - BACKGROUND: Real-time myocardial contrast echocardiography (MCE) makes possible
      the simultaneous visualization of changes in perfusion imaging and wall motion.
      OBJECTIVES: To assess the accuracy of real-time MCE for detecting the presence
      and extent of coronary artery disease (CAD), and to evaluate the correlation
      between wall motion and myocardial perfusion by visual examination. METHODS: A
      total of 140 consecutive patients without resting wall motion abnormalities were
      screened to undergo dobutamine stress MCE with power modulation and coronary
      angiography. Significant coronary disease was defined by the quantification of
      over 50% stenosis in a major epicardial vessel. The visual identification of wall
      motion and myocardial perfusion abnormalities was determined by blind review.
      RESULTS: Eight patients were excluded due to suboptimal images (feasibility
      94.3%). Myocardial contrast enhancement analysis and wall motion analysis were
      similar in terms of sensitivity (81.2% versus 83.5%, respectively) and
      specificity (76.5% versus 80.9%, respectively) in detecting the presence of CAD.
      Myocardial contrast enhancement analysis tended to have a greater sensitivity
      than wall motion analysis in detecting the ischemic extent over multiple vascular
      territories among patients with multiple-vessel disease (sensitivity 83.8% versus
      71.4% [P=0.09], and abnormal segment length 54.7+/-21.1% versus 48.9+/-24.7%
      [P=0.03] for myocardial contrast enhancement and wall motion analysis,
      respectively). There was good concordance between the presence of myocardial
      ischemia and wall motion abnormality for the segment-by-segment analysis (89.7%
      agreement, kappa = 0.745). The correlation of the wall motion score and perfusion
      score at peak stress was also good (r=0.793, P=0.015). CONCLUSIONS: Dobutamine
      stress MCE with power modulation is similar in sensitivity and specificity to
      wall motion analysis for detecting the presence of CAD. However, it provides
      greater sensitivity in evaluating the extent of ischemia in patients with
      multiple-vessel disease.

PMID- 15494777
TI  - Brain natriuretic peptide predicts successful cardioversion in patients with
      atrial fibrillation and maintenance of sinus rhythm.
AB  - BACKGROUND: Brain natriuretic peptide (BNP) is released from the heart by
      hemodynamically induced muscle stretch. Patients with atrial fibrillation have
      higher levels of BNP than those in sinus rhythm. OBJECTIVE: To assess the
      usefulness of BNP as a predictor of successful cardioversion in patients with
      persistent atrial fibrillation and subsequent maintenance of sinus rhythm.
      SUBJECTS AND METHODS: Twenty patients undergoing cardioversion for persistent
      atrial fibrillation were enrolled. BNP levels were measured before electric
      cardioversion, and 30 min and two weeks after cardioversion. Baseline
      echocardiograms and 12-lead electrocardiograms were obtained from all patients.
      Patients with valvular disease, previous mitral valve surgery or significant left
      ventricular dysfunction were excluded. RESULTS: The mean BNP level and the mean
      heart rate were significantly higher before cardioversion than 30 min after
      (197+/-132 pg/mL versus 164+/-143 pg/mL, P=0.02, and 77+/-17 beats/min versus
      57+/-12 beats/min, P=0.0007, respectively). Patients who reverted back to atrial
      fibrillation after two weeks had a baseline BNP of 293+/-106 pg/mL, while those
      who remained in sinus rhythm for two weeks had a lower baseline BNP of 163+/-122
      pg/mL (P=0.02). CONCLUSION: In patients with persistent atrial fibrillation, BNP
      levels are associated with successful cardioversion and maintenance of sinus
      rhythm two weeks after cardioversion.

PMID- 15494778
TI  - The Ontario Cardiac Rehabilitation Pilot Project: Recommendations for health
      planning and policy.
AB  - BACKGROUND: Expansion of cardiac rehabilitation (CR) could save both lives and
      costs by reducing illness and use of health care services. In February 2001, the
      Ontario Ministry of Health and Long-Term Care (the Ministry) announced a pilot
      project (the Pilot) to implement and evaluate a comprehensive, multifactoral
      model of CR service delivery at 17 centres across Ontario. OBJECTIVES: To design,
      coordinate and evaluate a coordinated model of CR service delivery, and to
      collect and evaluate an extensive set of clinical and administrative data.
      METHODS AND RESULTS: The Pilot was a large, province-wide observational
      investigation of a health service delivery model for CR and secondary prevention
      care. The present paper is the third in a three-part, policy-related series. In
      the present paper, the results of the evaluation of the service delivery model
      and the final health policy recommendations that were made to the Ministry in
      September 2002 are presented. CONCLUSIONS: Within approximately one year, 4922
      patients were enrolled in the Pilot at participating sites throughout Ontario;
      88% of sites implemented all elements of the comprehensive services model, either
      on-site or through internal/external partnerships, and 94% of sites implemented
      the multidisciplinary Pilot staffing model. Based on this rapid and near-total
      implementation of the Pilot model, it was concluded that the Pilot model of care
      was generalizable. Furthermore, regional coordination was achieved through
      operationalization of the coordinating centres' roles in quality management,
      regional planning and program development, education and outreach.

PMID- 15494779
TI  - Cardiac rehabilitation: Cost and care effective.

PMID- 15494781
TI  - The importance of negative and neutral clinical trials.

PMID- 15494780
TI  - Health-related quality of life outcomes of patients with coronary artery disease
      treated with cardiac surgery, percutaneous coronary intervention or medical
      management.
AB  - BACKGROUND: Given the repeated findings of little or no difference in mortality
      outcomes between percutaneous coronary intervention (PCI) with or without stent
      and coronary artery bypass graft surgery (CABG), there is a need to assess the
      health-related quality of life (HRQOL) outcomes associated with revascularization
      decisions. OBJECTIVE: To compare risk-adjusted HRQOL outcomes by treatment
      strategy one year following cardiac catheterization. METHODS: Using an inception
      cohort study design, the sample included all Alberta residents, 18 years of age
      or older, referred for cardiac catheterization, from January 1, 1996, to December
      31, 1998, with two or more diseased coronary vessels at catheterization. Patients
      received a follow-up questionnaire including the Seattle Angina Questionnaire
      (SAQ), one year following their index catheterization. The SAQ comprises five
      dimensional scales measuring exertional capacity, anginal stability, anginal
      frequency, treatment satisfaction and quality of life. RESULTS: Three thousand
      three hundred ninety-two (78.1%) patients responded to the follow-up survey.
      Responders who were revascularized consistently reported significantly better
      HRQOL compared with responders treated with medical management. Responders
      undergoing CABG reported significantly better HRQOL in all but one SAQ dimension
      compared with responders who had either a PCI with or without stent. Responders
      who had a PCI with stent reported better HRQOL compared with responders who
      underwent a PCI without a stent. CONCLUSION: The treatment decision to
      revascularize the coronary vessels, whether with PCI with or without a stent or
      with CABG, was consistently associated with significantly better HRQOL at one
      year follow-up compared with patients treated with medical therapy.

PMID- 15494789
TI  - Weighing the evidence: prospects for evidence-based policy-making.
AB  - Evidence-based policy (EBP) is currently one of the "big ideas" in policy
      circles. From its origins in the medical community, EBP is now being applied to
      other policy domains including environment. But will it really ensure that the
      public policy grease gets to the environmental squeak? And what are the
      implications for scientists themselves?

PMID- 15494791
TI  - Research profile. Martin Harper.

PMID- 15494794
TI  - Improvement of research and biomedical publication.

PMID- 15494795
TI  - Enhancing research productivity in the Arab world.

PMID- 15494796
TI  - Family and community medicine in Saudi Arabia. Development and future.

PMID- 15494797
TI  - Biomedical science journals in the Arab world.
AB  - Medieval Arab scientists established the basis of medical practice and gave
      important attention to the publication of scientific results. At present, modern
      scientific publishing in the Arab world is in its developmental stage. Arab
      biomedical journals are less than 300, most of which are published in Egypt,
      Lebanon, and the Kingdom of Saudi Arabia. Yet, many of these journals do not have
      on-line access or are indexed in major bibliographic databases. The majority of
      indexed journals, however, do not have a stable presence in the popular PubMed
      database and their indexes are discontinued since 2001. The exposure of Arab
      biomedical journals in international indices undoubtedly plays an important role
      in improving the scientific quality of these journals. The successful examples
      discussed in this review encourage us to call for the formation of a consortium
      of Arab biomedical journal publishers to assist in redressing the balance of the
      region from biomedical data consumption to data production.

PMID- 15494798
TI  - Isolation versus quarantine and alternative measures to control emerging
      infectious diseases.
AB  - In the past 25 years, the world has witnessed the emergence and re-emergence of
      many infectious diseases. In the early stages of their emergence, isolation and
      quarantine may be the only and last resort to effectively control infectious
      diseases when we are confronted with limited or no knowledge of a newly
      identified and previously unknown contagious disease, which causes a serious
      public health threat either locally or internationally. The article traces back
      the origins of isolation and quarantine; defines precisely the terms isolation
      and quarantine as they are currently used in the modern era; compare and contrast
      these terms; identifies some of the harmful consequences of applying quarantine
      measures; highlights considerations for the use of isolation and quarantine; and
      identifies alternative measures adopted by the world health community to respond
      to emerging and re-emerging health threats.

PMID- 15494799
TI  - Endocrinopathies in patients with thalassemias.
AB  - Thalassemia major is a hereditary disorder of hemoglobin synthesis resulting in
      severe anemia. Treatment consists of multiple blood transfusions, a complication
      of which is iron overload. Excessive iron is then deposited in almost all tissues
      but primarily in the liver, heart and the endocrine glands. Lately,
      desferrioxamine has been used as a chelating agent in an attempt to prevent the
      complications of tissue damage by iron deposition. Early introduction of the
      chelating agent to combat iron overload in vulnerable organs leads to improved
      life expectancy. However, these patients often present with multiple endocrine
      dysfunction such as growth failure, hypogonadism, abnormalities in glucose
      metabolism, hypothyroidism, hypoparathyroidism and less frequently
      hypoadrenalism. We briefly review the current status of endocrine gland
      abnormalities in patients with thalassemia major.

PMID- 15494800
TI  - Structural study on cultured isolated fetal rat pancreatic islets.
AB  - OBJECTIVE: To perform a morphometric and structural study of the cultured
      isolated fetal rat pancreatic islets. METHODS: Islets of the fetal rat pancreas,
      aged 22 days were isolated by the standard procedure of collagenase digestion and
      culture technique. The islets were cultured for 1, 2, 3, 4 and 5 days. The islets
      were counted under a dissecting microscope and islet diameter and purity were
      measured under a phase contrast microscope fitted with a calibrated grid. The
      islet specimens were fixed in buffered neutral formalin, dehydrated in alcohol
      and embedded in parablast. Sections were stained with hematoxylin and eosin. This
      study was conducted in King Fahd Medical Research Center, Faculty of Medicine,
      King Abdul-Aziz University, Kingdom of Saudi Arabia, during 2003 and 2004.
      RESULTS: The purity of the cultured islets gradually increased with time and was
      significantly different between the cultured groups. The number of the cultured
      islets gradually decreased with time. The islet diameter gradually increased with
      culture period. The islet purity and diameter were significantly different
      between the cultured groups. Parablast sections stained with hematoxylin and
      eosin showed that the shape and histological structure of the cultured islets
      were intact. CONCLUSION: The results of the present work represent an extensive
      morphometric structural study of isolated cultured fetal islets. The culture
      islet diameter and purity showed gradual increase with culture period, while the
      islet number showed gradual decrease.

PMID- 15494801
TI  - The effects of chronic consumption of heroin on basal and vagal electrical
      stimulated gastric acid and pepsin secretion in rat.
AB  - OBJECTIVE: Addiction to opium and heroin is not only an important social and
      individual problem in the world but it also affects the human physiology and
      multiple systems. The aim of this study is to determine the effects of chronic
      heroin consumption on basal and vagus electrical-stimulated total gastric acid
      and pepsin secretion in rats. METHODS: The study was carried out in the
      Department of Physiology, Kerman University of Medical Sciences, Iran from August
      2002 to June 2003. Both male and female rats weighing 200-250 g were used. Rats
      received daily doses of heroin intraperitoneally starting from 0.2 mg/kg to 0.1
      mg/kg/day up to the maintenance level of 0.7 mg/kg and continued until day 12.
      After anesthesia, tracheotomy and laparotomy, gastric effluents were collected by
      washout technique with a 15 minutes interval. The total titrable acid was
      measured by manual titrator, and the total pepsin content was measured by Anson's
      method. Vagal electrical stimulation was used to stimulate the secretion of acid
      and pepsin. RESULTS: Heroin results in a significant decrease in total basal acid
      and pepsin secretions (4.10 +/- 0.18 mmol/15 minutes versus 2.40 +/- 0.16 mmol/15
      minutes for acid, p<0.01, and 3.63 +/- 0.18 mg/15 minutes versus 3.11+/- 0.18
      mg/15 minutes for pepsin, p<0.05). But, it does not produce any significant
      changes in acid and pepsin secretions in vagotomized condition. Heroin also
      causes a significant decrease in vagal-electrically stimulated acid and pepsin
      secretions (14.70 +/- 0.54 mmol/15 minutes versus 4.30 +/- 0.21 mmol/15 minutes
      for acid, p<0.01, and 3.92 +/-0.16 mg/15 minutes versus 3.37+/- 0.16 mg/15
      minutes for pepsin, p<0.05). CONCLUSION: Heroin consumption decreases the total
      gastric basal and vagus stimulation of acid and pepsin secretion, but not in
      vagotomized condition. Heroin may decrease acid secretion by inhibiting vagal
      release of acetylcholine within the gastric wall. Other probable mechanisms
      include: presynaptic inhibition of acetylcholine release or depressing the vagal
      center, inhibition of pentagastrin induced acid secretion, inhibitory effects via
      central mechanisms, probably mediated by the opiate receptors. Further studies
      are needed to recognize the actual mechanism.

PMID- 15494802
TI  - Ultrastructural alterations in renal tissues of rabbits induced by diclofenac
      sodium (Voltaren).
AB  - OBJECTIVE: Although diclofenac sodium (Voltaren) is one of the most frequently
      prescribed non-steroidal anti-inflammatory drugs (NSAIDs) worldwide for the
      treatment of inflammation and pain; data on the ultrastructural alterations in
      renal tissues due to its chronic exposure are limited. Therefore, the present
      study was designed to identify the ultrastructural renal alterations induced by
      diclofenac sodium. METHODS: The experiment was conducted at the animal house of
      the Department of Zoology, College of Science, King Saud University, Riyadh,
      Kingdom of Saudi Arabia during the period from April 2003 to June 2003. A total
      of 30 male rabbits were exposed to intraperitoneal injection with a daily dose of
      diclofenac sodium (1.5 mg/kg body weight) for 70 days to investigate the
      resultant ultrastructural alterations in renal tissues. RESULTS: In comparison
      with the respective control rabbits, chronic exposure to therapeutic doses of
      diclofenac sodium produced significant ultrastructural renal alterations, which
      involved swelling and cristolysis of the mitochondria, marked dilatation of the
      endoplasmic reticulum, detachment of ribosomes, increased lysosomal structures,
      nuclear chromatin condensation in the tubular cells, thickening of the glomerular
      basement membranes, distention of glomerular capillaries, which showed lodgment
      of neutrophils, mesangial and endothelial cell proliferation in the glomeruli,
      swelling and fusion of the glomerular podocytes foot processes with focal
      obliteration of the filtration slits. CONCLUSION: The obtained results indicate
      that chronic exposure to diclofenac sodium produces significant ultrastructural
      alterations in renal tissues.

PMID- 15494803
TI  - Improving organ donation in Central Saudi Arabia.
AB  - OBJECTIVE: Organ transplantation is successful. The main challenge in the Kingdom
      of Saudi Arabia (KSA) and elsewhere continues to be organ shortage. This shortage
      was not resolved by utilization of living donors. Previous studies indicate that
      there is underreporting of brain death cases, lack of completion of documentation
      process, poor medical care in some instances and finally high refusal rate for
      consent. In order to put this problem in perspective and find a solution, we
      initiated a collaborative project between 4 hospitals in Riyadh, KSA and The
      Saudi Center for Organ Transplantation. The initial result of this project is
      presented in this article. METHODS: A donor team was formed to deal and
      facilitate the logistical aspect of donation in the 3 main Ministry of Health
      hospitals in Riyadh. Data with regard to the number of donors reported,
      documentation and success rate were recorded over 3-months (October 2003 to
      December 2003) and compared with the preceding 9 months. RESULTS: During the
      period from January 2003 to September 2003, the total number of case reported to
      the Saudi Center for Organ Transplantation in Riyadh region, was 94. Only 53%
      were fully documented. Families were approached in 45 of these 50 cases in terms
      of donation and consent was obtained in 15. However, the number harvested was
      only 10 (11% yield from total number reported). During the period from October
      2003 until the end of December 2003, the total number of cases reported from 3
      hospitals was 19. Seventeen (90%) of them were documented. The families were
      approached in 16 cases and consent was obtained in 6. All 6 (32%) donors were
      harvested. CONCLUSION: The above result clearly indicates that a donor team
      supporting the intensive care unit (ICU) can improve the donation. It is expected
      that application of a similar project to more ICUs in KSA will have a substantial
      positive impact on the rate of organ donation.

PMID- 15494804
TI  - Pain relief using continuous bupivacaine infusion in the paravertebral space
      after loin incision.
AB  - OBJECTIVE: Continuous bupivacaine paravertebral nerve block after thoracotomy has
      been shown to reduce postoperative pain. This study was designed to determine
      whether paravertebral nerve block using bupivacaine infused through a catheter
      placed intraoperatively, can reduce postoperative pain, and analgesia
      requirements after loin incision. METHODS: Thirty-four patients undergoing renal
      surgery through loin incision at Jordan University Hospital, Amman, Jordan, from
      October 2001 to March 2003, were randomized either to receive bupivacaine 0.5% or
      normal saline through a catheter positioned intraoperatively against the
      costovertebral joints in the paravertebral space. The infusions were continued
      until the evening of the third postoperative day. Patients had access on request
      to intramuscular Morphine sulphate 5-15 mg, or Diclofenac sodium 50-100 mg, or
      both depending on body weight. Pain after operation was assessed at rest using
      linear visual analogue scale. Patient scores were recorded in the recovery room,
      at 4 hours, 8 hours, and at 9 am, and 5 pm. RESULTS: The analgesia requirements
      for each patient were recorded. Pain scores in the recovery room were
      significantly lower in the bupivacaine group (mean 4.5 versus 8.0, p=0.001). At 4
      hours, the pain score was lower in the bupivacaine group though not significant
      (mean 3.5 versus 4.37, p=0.393). Thereafter, the pain scores were significantly
      lower in the bupivacaine group. Mean morphine requirement in the bupivacaine
      group was 13.3 mg (ranges 0-50), while in the saline group 40.13 mg (range 10
      112.5), p<0.001. Morphine requirements in the first and second postoperative days
      were significantly less in the bupivacaine group (p=0.015 and p=0.03).
      CONCLUSION: Paravertebral blockade using bupivacaine is an effective and safe
      method for pain relief following renal surgery through loin incision.

PMID- 15494805
TI  - Ultrasound guided fine needle aspiration using 25G needle as a new technique for
      a wide range of pathological conditions.
AB  - OBJECTIVE: This study is to report on the use of 25 gauge (G) needle in
      ultrasound (US) guided fine needle aspiration (FNA), as a new technique for a
      wide range of pathological conditions, and to assess the yield of positive tissue
      material and the complications compared to those reported in the literature using
      larger needles. METHODS: One hundred and seventy-two patients presented
      consecutively at King Saud University Teaching Hospitals, Kingdom of Saudi
      Arabia, during the period 2000 to 2002, with various pathological conditions,
      underwent US guided FNA using 25G needle. The adequacy of the tissue obtained,
      and the pathological outcome were tabulated. The patients were discharged in the
      same day and followed for 4-6 weeks for complications. RESULTS: Adequate tissue
      was obtained from 165 (96%) patients. Seven (4.1%) patients had to be examined
      twice, to obtain a sufficient sample. The 172 patients also included 14 patients
      (8.1%) who had repeated procedure on the request of the clinician, who needed
      confirmation of the pathological diagnosis. Adequate sampling was obtained in the
      first attempt in 89%, in liver problems, and in other regions, and 86.8% in lung
      problems. The percentages of diagnostic categories revealed by the cytological
      analysis are similar to those obtained by other larger fine needles. CONCLUSION:
      No complications have been encountered. The technique can safely be repeated if
      the amount is inadequate or diagnosis is inconclusive, to reach 100% correct
      sampling. The results of positive findings are comparable to other studies using
      larger needles. The use of 25G needle is recommended for use under ultrasound
      guidance.

PMID- 15494806
TI  - Volume assessment of age-related conversion of the tympanic cavity by helical
      computerized tomography scanning.
AB  - OBJECTIVE: To investigate the right-left asymmetry, and gender and age groups
      differences of the tympanic cavities (TC) using the Cavalieri principle for
      volume calculation on temporal bone computerized tomography (CT) scans. METHODS:
      This study was carried out over a 4-year period from 2000 to 2004 at Firat
      University, School of Medicine, Elazig, Turkey. The areas of the cavities were
      measured using trace and area measurement functions of CT scanner, and by
      multiplying the area by slice thickness (0.2 cm) and the volume of each slice was
      calculated. By summing all volumes of every slice based on the Cavalieri
      principle for volume calculation, the total volumes were obtained and analyzed.
      RESULTS: The mean (SD) volumes of right and left tympanic cavities in males were
      0.52 (0.15) versus 0.55 (0.14) cm3 and in females were 0.45 (0.16) versus 0.49
      (0.14) cm3, and there were statistically significant differences between males
      and females in both right and left sides (p=0.028 and p=0.043). There was a
      statistically significant difference in left TC volumes between age groups
      (p=0.019). However, no differences by age were noted for right TC volumes
      (p=0.065). A strong correlation was found between right and left volumes.
      However, there were no strong correlations between age and volumes of right and
      left cavities in both males and females, although the volumes increased by aging.
      CONCLUSION: These results should help surgeons and radiologists to update their
      knowledge for evaluation of the middle ear region.

PMID- 15494807
TI  - High independence level in functional activities reduces hospital stay after
      total hip arthroplasty regardless of pain intensity.
AB  - OBJECTIVE: The purpose of this study is to investigate the relationship between
      independence level in functional activities and pain, and length of hospital stay
      in the early postoperative period in patients with total hip arthroplasty (THA).
      METHODS: The study was performed over 26 end stage hip arthritis patients who
      were hospitalized in the Department of Orthopedics and Traumatology, Hacettepe
      University Hospital, Ankara, Turkey, between January 2000 and July 2003 for THA
      and operated with the same surgical technique by the same surgeon. All patients
      were mobilized in the first postoperative day and a standard rehabilitation
      protocol was applied to all patients. The independence level in functional
      activities of the cases was assessed with Iowa Level of Assistance Scale (ILAS).
      Iowa Ambulation Speed Scale (IASS) was used to evaluate the speed of ambulation
      in the early postoperative period. Pain was assessed with visual analogue scale
      (VAS). RESULTS: There was no statistically significant relation between pain
      intensity and independence level in functional activities on the second and sixth
      postoperative days (p>0,05), but independence level scores in functional
      activities on the second and sixth days were correlated with hospital stay length
      (p<0.05). CONCLUSION: The results of this study indicate that in patients with
      THA, pain does not affect the independence level in functional activities in the
      early postoperative period. In the same period as the independence level
      improves, the hospital stay length decreases. This is an important factor that
      may reduce both the hospital costs and the possible complications due to
      prolonged hospital stay.

PMID- 15494808
TI  - Magnitude and determinants of refractive error in Omani school children.
AB  - OBJECTIVE: To estimate the magnitude and determinants of refractive error in
      school children, a study was undertaken to review the school screening and
      refraction data. METHODS: Trained physicians screened 416,157 students to
      evaluate their visual status and identified 28,765 students with defective
      vision. Refractionists refracted 25,733 (89.5%) of them, determined the
      refractive error and prescribed spectacles. Students with ocular co-morbidity and
      visual disability were re-examined and treated by the ophthalmologists. This
      study was conducted between June 2003 and December 2003 in the Ministry of
      Health, Muscat, Sultanate of Oman. RESULTS: The prevalence of myopia was 4.1%
      (95% confidence interval [CI] 4.06-4.18). It was higher among female than male
      students [rate ratio (RR) 1.69 (95% CI 1.64-1.74)]. The rate was more in students
      of higher age groups (chi2 = 11,179 degrees of freedom = 2 p<0.00001). Regional
      variation in myopic trend was marked. The prevalence of hypermetropia was 0.4%
      (95% CI 0.37-0.41). However, it could be an underestimation as presence of
      accommodative spasm was not taken into account. The risk of low vision disability
      was significantly higher in male students than female students. The prevalence of
      ambiopia was 0.3%. It was significantly higher in male than female students.
      First primary students had strabismus of 0.5%. CONCLUSION: The study enabled to
      understand trends of refractive error in Omani children (Arabic tribe) and
      demonstrated the importance of vision screening in providing timely eye care and
      identifying visually disabled school children.

PMID- 15494809
TI  - Obstetric admissions to the intensive care unit.
AB  - OBJECTIVE: To describe clinical characteristics, interventions required, and
      outcome of critically ill obstetric patients admitted to a general intensive care
      unit (ICU). METHODS: All obstetric patients admitted to ICU at Armed Forces
      Hospital, Riyadh, Kingdom of Saudi Arabia from 1997 to 2002 were included in the
      study. The data related to demographics, obstetric history, pre-existing medical
      problems, indications for ICU admission, intervention required, length of stay,
      and outcome of ICU admission were collected by retrospective review of medical
      records. RESULTS: The 99 obstetric admissions to ICU were represented by 0.2% of
      all deliveries and 1.6% of all ICU admissions. Most patients were young (median
      age of 30 years) with parity (median) of 3 and stayed in ICU for an average of 2
      days. All except one patient were admitted during the postpartum period. The
      majority (76%) were admitted after cesarean section. Obstetric hemorrhage (32%)
      and hypertension (29%) were the 2 most common indications for admission. The
      majority (59/99) of patients also had pre-existing medical problem and most
      common (16/59) was rheumatic heart disease. Preeclampsia (23/99) and eclampsia
      10/99 were the most frequent obstetric complication. Thirty-six percent of our
      patients required ventilatory support. In the majority of patients, direct
      arterial (81%) and central venous (73%) pressure monitoring was carried out.
      Pulmonary arterial and left atrial pressure was monitored in 4%. Almost one third
      of patients received antihypertensive therapy. Inotropic support was given to 9%
      and blood (and its products) was given to 46% of patients. Antibiotics (28%) and
      magnesium sulphate (25%) were the most frequently used medicines. Out of the
      total 99 admissions, one patient died and 16 patients developed complications.
      CONCLUSION: In our survey, the 2 most common indications for admitting obstetric
      patients to ICU were hemorrhage and hypertension. Invasive hemodynamic monitoring
      and ventilatory support are the 2 main interventions. Improving quality of care
      before and after admission to ICU may reduce maternal morbidity.

PMID- 15494810
TI  - Mefloquine in the treatment of falciparum malaria during pregnancy in Eastern
      Sudan.
AB  - OBJECTIVE: To test the efficacy and toxicity of mefloquine therapy both on
      expectant mothers and the outcome of their pregnancies. METHODS: We performed a
      prospective non-comparative clinical trial in New Halfa Teaching Hospital,
      Eastern Sudan, during the period October 1998 to June 2001. Pregnant Sudanese
      women were given mefloquine 25 mg/kg for treatment of falciparum malaria
      following chloroquine failure. The women were followed every 2 weeks in the
      antenatal clinic until delivery. The babies were followed until the age of one
      year. RESULTS: Forty pregnant women were enrolled in the second and third
      trimesters. Itching which occurred in 17.5% and nausea which occurred in 35% were
      the cardinal side effects of the patients. Recrudescence or re-infection occurred
      on day 14 in one patient (2.5%). One patient that received mefloquine at 34 weeks
      gestational age delivered low birth weight (2.1 kg) at 39 weeks gestational age.
      One child died at the age of 7 months due to unexplained febrile illness. There
      was no abortion, no stillbirth and no congenital abnormality in the newborn
      children and no maternal death. CONCLUSION: This relatively small study reported
      that mefloquine could be used safely for the treatment of malaria in the second
      and third trimester of pregnancy and a larger study is recommended.

PMID- 15494811
TI  - Investigation of the antibiotic susceptibility patterns of pathogens causing
      nosocomial infections.
AB  - OBJECTIVE: The aim of this study is to determine the resistance patterns of
      bacteria causing nosocomial infections. The outcome of this resistance was
      followed for 3 years. METHODS: This study was carried out during 2000 to 2002 at
      a university hospital in Turkey. The resistance patterns of 570 bacteria (390
      Gram-negative, 180 Gram-positive) against meropenem, imipenem, ceftazidime,
      cefotaxime, cefepime, piperacillin/tazobactam, ciprofloxacin and tobramycin were
      investigated using the E-test. Extended-spectrum beta-lactamase (ESBL) production
      was determined using ceftazidime and ceftazidime/clavulanic acid E-test strips.
      RESULTS: Meropenem was the most effective antibiotic against Gram-negative
      organisms (89.0%); this was followed by imipenem (87.2%) and
      piperacillin/tazobactam (66.4%). The most active antibiotic against Gram-positive
      bacteria was imipenem (87.2%) and this was followed by piperacillin/tazobactam
      (81.7%) and meropenem (77.8%). The rates of production of ESBL by Escherichia
      coli were 20.9%, Klebsiella pneumoniae 50% and Serratia marcescens were 46.7%.
      Extended-spectrum beta-lactamase production increased each year (21.7%, 22.1% and
      45.5%). All of the ESBL producing isolates were sensitive to meropenem and 98.5%
      sensitive to imipenem. AmpC beta-lactamase was produced by 20.9% of the
      Enterobacter species spp, Citrobacter spp. and Serratia marcescens. All of these
      were sensitive to meropenem and 77.8% to imipenem and ciprofloxacin. Multi-drug
      resistance rates in Acinetobacter spp were 45.4% and 37.7% in Pseudomonas
      aeruginosa isolates. CONCLUSION: As in the entire world, resistance to
      antibiotics is a serious problem in our country. Solving of this problem depends
      primarily on prevention of the development of resistance.

PMID- 15494812
TI  - Changes in epidemiological pattern of Meningococcal disease in Saudi Arabia. Does
      it constitute a new challenge for prevention and control?
AB  - OBJECTIVE: Meningococcal meningitis epidemics, which occurred in the Kingdom of
      Saudi Arabia (KSA) coincided with Hajj and Umra seasons; the 2 major pilgrims to
      Muslims. In many countries, the disease showed major changes of its
      epidemiological determinants, in particular to age and prevailing serogroup. This
      study was conducted to determine the epidemiological trend of meningococcal
      meningitis disease in KSA. METHODS: All confirmed meningococcal meningitis cases
      reported in KSA during the period from January 1999 to December 2002 were studied
      retrospectively. Confirmation of cases was based on isolation of the causative
      organism from cerebrospinal fluid (CSF) or blood culture or detection of antigen
      in the CSF. Personal, clinical and laboratory results were analyzed using Epi
      info version 6 software. Categorical data were tested using chi2 test. RESULTS: A
      total of 729 cases were reported, 304 cases (42%) were among people coming from
      abroad for Hajj or Umra and 425 (58%) were among local population. Nearly half of
      the later (48%) were reported at the 2 holy areas of Makkah and Madinah, KSA.
      Thirty-nine percent of cases were children aged <2 years and 58% were <5 years of
      age. Proportion of cases affected with serogroup W135 increased over time (up to
      95%) and significantly affected children aged <5 years (p<0.001). CONCLUSION:
      Continuous monitoring of epidemiological determinants is essential to guide
      vaccination policy.

PMID- 15494813
TI  - Effectiveness of hepatitis B vaccination in children of chronic hepatitis B
      mothers.
AB  - OBJECTIVE: Although all newborns in Iran have been vaccinated against hepatitis B
      since March 1993, routine screening of pregnant women has not been conducted in
      prenatal care programs, yet transmission of hepatitis B via the maternal-fetal
      route is still a viable likelihood, which must be entertained. METHODS: The
      subjects were divided into 2 groups. The exposed group comprised 97 vaccinated
      children whose mothers were seropositive for hepatitis B surface antigen (HBsAg)
      and had not received hepatitis immunoglobulin at birth. The unexposed group
      consisted of 87 vaccinated children whose mothers were seronegative for hepatitis
      B surface antigen. We compared these 2 groups to determine the efficacy of
      vaccine alone in high-risk children. This study was conducted in Tehran, Iran,
      from June 2002 to December 2002. All children were born after 1993. RESULTS:
      Chronic infection (HBsAg positivity) was detected in 14.3% of children in the
      exposed group. There were no instances of chronic infection in the unexposed
      group (relative risk [RR]=13.48, 95% confidence intervals [CI] 1.8-100.02).
      Previous infection of hepatitis B (HBcAb positivity) was found in 29 (29.9%)
      children in the exposed group, but only one (1.2%) in the unexposed group
      (RR=26.01, 95% CI: 3.61-186.95). Immunity (HBsAb positivity) in the exposed group
      measured 48 (49.5%) and unexposed group measured 56 (64.4%) (R.R=0.76, 95% CI:
      0.59-0.99). CONCLUSION: Vaccination alone did not induce immunity against
      hepatitis B in high-risk children; it seems that routine screening of pregnant
      women is necessary for determining whether neonates need hepatitis B
      immunoglobulin after birth.

PMID- 15494814
TI  - Prevalence of human T-lymphotropic virus type I and type II antibody among blood
      donors in Eastern Saudi Arabia.
AB  - OBJECTIVE: Human T-cell leukemia/lymphoma virus type I and type II (HTLV-I/II)
      infections can be transfusion associated, leading to tropical paraparesis,
      myelopathy and other neurological disorders. The aim of this study is to
      circumvent the risk of transmission through blood transfusion and to describe the
      prevalence of HTLV-I/II antibody among blood donors of Al-Hasa region and the
      cost effectiveness of screening blood donors. METHODS: The study was conducted at
      the Department of Laboratory and Blood Bank, King Fahad Hospital, Al-Hofuf, Al
      Hasa, Kingdom of Saudi Arabia during the period of 1997 to 2003. A total of 47426
      blood donors were screened for HTLV-I/II antibody by enzyme-linked immunosorbent
      assay test, during the 7 years of study period. The positive samples were
      confirmed by western blot analysis. RESULTS: Overall, HTLV-I antibody positivity
      (confirmed by western blot) was 3/47426 (0.006%). Out of 3 donors positive for
      HTLV-I antibody during 1997 to 1998, 2 were expatriates (Indian) and one was
      native Saudi donor. Human T-cell leukemia/lymphoma virus type I antibody
      positivity among the native Saudi donors was 1/47426 (0.002%) (2/100000 blood
      donors). None of the donor were positive for HTLV-II antibody. During the last 5
      consecutive years of the study period (1999-2003), none of the donor was positive
      for HTLV-I/II antibody. CONCLUSION: Al-Hasa region is non-endemic for HTLV-I/II
      virus infections. Screening of native Saudi blood donors for these viruses does
      not appear to be cost effective.

PMID- 15494815
TI  - Prevalence of osteoporosis among postmenopausal females with diabetes mellitus.
AB  - OBJECTIVE: To assess the prevalence of osteopenia and osteoporosis among Saudi
      postmenopausal women with non-insulin dependent type 2 diabetes mellitus (T2DM).
      METHODS: The study was carried out at King Khalid University Hospital, Riyadh,
      Kingdom of Saudi Arabia from February 2000 to September 2002. Bone mineral
      density (BMD) of the lumbar spine and femoral neck using dual x-ray
      absorptiometry (DXA; Lunar Wisconsin), were performed in 104 postmenopausal Saudi
      women with T2DM, and 101 postmenopausal non-diabetic women (control). Bone
      mineral density was measured in gm/cm2 and both T-score and Z-score were measured
      but only T-score was used for analysis based on World Health Organization
      criteria. Bone profile, 25(OH) Vitamin D, 1,25(OH)2 Vitamin D, parathyroid
      hormone and urine deoxypyridinoline (DPD) were measured in most patients and
      controls. Body fat measurement around the biceps muscles using Futrex (body
      composition analyzer) were performed in patients and controls. Years
      postmenopausal, duration of diabetes mellitus, parity, exercise, sun exposure and
      milk consumption were also recorded. RESULTS: In the diabetic group, the mean
      spine BMD was 0.928 gm/cm2 (T-score = -2.28 SD) and for femoral neck the mean BMD
      was 0.817 gm/cm2 (T-score = -1.21 SD). In control group, the mean spine BMD was
      1.036 gm/cm2 (T-score = -1.2) and mean femoral neck BMD was 0.914 gm/cm2 (T-score
      = -0.608). In the diabetic group, there was 16 (16.64%) patients with normal BMD
      of the spine, 42 patients (43.68%) with osteopenia (mean T-score = -1.8 SD) and
      45 (46.8%) with osteoporosis (mean T-score = -3.3 SD). CONCLUSION: Osteoporosis
      is more common among Type 2 postmenopausal females in this ethnic group. Since
      both groups are postmenopausal, having equal percentage of Vitamin D deficiency,
      multi-parity, non exposure to sun, lack of exercise and negligible milk intake,
      one can conclude that the low BMD can be attributed to DM in the absence of other
      causes of osteoporosis.

PMID- 15494816
TI  - Clinical and endocrine aspects of pituitary tumors.
AB  - OBJECTIVE: To study the clinical spectrum and endocrine profile of pituitary
      tumors presenting to a tertiary care endocrine center. METHODS: Retrospective
      analysis of clinical and hormonal data of patients with pituitary tumors admitted
      in the Endocrinology Department of Sher-i-Kashmir Institute of Medical Sciences,
      Srinagar, Kashmir India between January 1989 and December 1998. RESULTS: Over a
      period of one decade, 75 subjects were diagnosed to have pituitary tumors.
      Somatotroph adenoma was the most common pituitary mass lesion seen (44/75) and
      followed in the decreasing order of frequency, by non-functioning pituitary tumor
      (12/75), prolactinoma (11/75) and corticotroph adenoma (8/75). Overall there was
      a male preponderance (male to female ratio was 41:34). Subjects with somatotroph
      adenoma presented with classical features of acromegaly: mean fasting and post
      glucose suppression growth hormone levels were 34.04+/-11.67 and 36.47+/-6.64
      ng/ml. Eleven subjects (9 females and 2 males) had prolactinoma; females
      presented with the classical symptom complex of amenorrhea-galactorrhea while
      males presented with headache, visual disturbances and impotence. The 12 subjects
      with nonfunctioning pituitary tumors presented with features of mass lesion. Of
      the 8 subjects (6 females and 2 males) with corticotroph adenomas, 2 were
      confirmed to have periodic hormonogenesis. CONCLUSION: In an endocrine center,
      functioning pituitary tumors are more often seen than non-functioning tumors.

PMID- 15494817
TI  - Prevalence of Helicobacter pylori infection among patients with dyspepsia in
      South-Western Saudi Arabia.
AB  - OBJECTIVE: Helicobacter pylori (H. pylori) infection is a major cause of various
      upper gastrointestinal (UGI) disorders. The aim of this study was to determine
      the prevalence of H. pylori among patients with dyspepsia. METHODS: A prospective
      study was carried out in the Gastroenterology Division, King Fahd Central
      Hospital, Gizan, Kingdom of Saudi Arabia from January 1995 to December 1998. Four
      hundred and eighty-eight patients with dyspepsia were consecutively examined
      using the UGI endoscopy during a 4-year period. Data analyzed included
      demographic details, clinical indications for the examination, endoscopic
      findings and results of the histopathologic assessment for H. pylori. RESULTS:
      Overall, H. pylori were detected in 268 (54.9%) of the gastric biopsies from 488
      patients (322 males and 166 females, aged 13-90 years). Helicobacter pylori
      infection was present in 140 (60.1%) of 253 patients with chronic gastritis
      diagnosed by endoscopy and in 49 (62.8%) of 78 patients with duodenal ulcers
      (DU). The rate in DU patients was significantly higher than the rate (43.6%) in
      patients with normal endoscopic findings (odds ratio [OR]=2.18, 95% confidence
      interval [CI] 1.02-4.70; p=0.04]. Of 455 biopsies with histologic gastritis, 268
      (OR=58.9%, 95% CI 54.2-63.4) were positive for H. pylori and all specimens (n=33)
      with no histological evidence of gastritis were negative. CONCLUSION: The well
      described association of H. pylori with DU and non-ulcer dyspepsia was confirmed
      by our study. However, the rate of H. pylori in our patients was at the lower end
      of the range (50-80%), which was previously reported among largely urban
      populations in Saudi Arabia suggests differences in the prevalence of H. pylori
      infections between urbanized and rural populations. Helicobacter pylori negative
      peptic ulcer disease remains an important entity that may be associated with the
      use of non-steroidal anti inflammatory drugs and in our environment, the habitual
      chewing of qat leaves (catha edulis).

PMID- 15494818
TI  - The effect of acetylsalicylic acid on the release rates of leukotrienes B4 and C4
      from cultured skin melanocytes of active vitiligo.
AB  - OBJECTIVE: The aim of this study is to investigate the effect of the non
      steroidal anti-inflammatory agent, acetylsalicylic acid (ASA), otherwise known as
      aspirin, at different concentrations on the release rates of the pro-inflammatory
      mediators, leukotriene B4 (LTB4) and leukotriene C4 (LTC4) from in vitro cultured
      melanocytes obtained from normal pigmented skin of patients with active vitiligo.
      METHODS: This study was carried out between April, 2000 and September, 2001, at
      The Vitiligo Unit, King Abdul-Aziz University Medical Center, Jeddah, Kingdom of
      Saudi Arabia. Skin biopsies were obtained from patients with active vitiligo
      (n=7) of different extent and duration, and normal healthy age-matched
      individuals (n=7) serving as control were recruited to the study. The release
      rates of LTB4 and LTC4 were determined before and after the addition of the ASA
      at 3 different concentrations (15, 75, 150 microg/ml) in the primary skin
      melanocytes culture medium using a commercially available kit based on
      radioimmunoassay method. RESULTS: Following the ASA treatment at 3 different
      concentrations (15, 75 and 150 microg/ml), the release rates of LTB4 and LTC4
      were increased from melanocytes of the normal individuals (13%, 7.5% and 30%;
      7.2%, 51.4% and 60.7%, p<0.001). However, in patients with active vitiligo, the
      release rate of LTB4 from melanocytes was decreased (2.9%, 14.4% and 7.4%,
      p<0.05), whereas that of LTC4 was increased (3.9%, 93.8% and 101.4%, p<0.001).
      CONCLUSION: Acetylsalicylic acid at therapeutic concentrations can regulate the
      release rates of LTB4 and LTC4 from cultured skin melanocytes of normal and
      active vitiligo subjects.

PMID- 15494819
TI  - Fc receptor gamma subunit polymorphisms and systemic lupus erythematosus.
AB  - OBJECTIVE: To investigate the possible association between Fc receptor (FcR)
      gamma polymorphisms and systemic lupus erythematosus (SLE). METHODS: We have
      investigated the full FcR gamma gene for polymorphisms using polymerase chain
      reaction (PCR)-single strand conformational polymorphism and DNA sequencing. The
      polymorphisms identified were genotype using PCR-restriction fragment length
      polymorphism. Systemic lupus erythematosus cases and controls were available from
      3 ethnic groups: Turkish, Spanish and Caucasian. The study was conducted in the
      year 2001 at the Arthritis Research Campaign, Epidemiology Unit, Manchester
      University Medical School, Manchester, United Kingdom. RESULTS: Five single
      nucleotide polymorphisms were identified, 2 in the promoter, one in intron 4 and,
      2 in the 3' UTR. Four of the 5 single nucleotide polymorphisms (SNPs) were
      relatively common and investigated in the 3 populations. Allele and genotype
      frequencies of all 4 investigated SNPs were not statistically different between
      cases and controls. CONCLUSION: Fc receptor gamma gene does not appear to
      contribute to SLE susceptibility. The identified polymorphisms may be useful in
      investigating other diseases where receptors containing the FcR gamma subunit
      contribute to the pathology.

PMID- 15494820
TI  - Naxos disease in an Arab family is not caused by the Pk2157del2 mutation.
      Evidence for exclusion of the plakoglobin gene.
AB  - OBJECTIVE: Naxos disease is a rare hereditary disorder characterized by
      palmoplantar keratoderma, woolly hair and cardiomyopathy. This study aims to
      determine whether Naxos disease in a Saudi Arab family is caused by the
      Pk2157del2 mutation that was identified in Greek families from Naxos Island where
      the disease had originally been described. METHODS: This study was undertaken at
      King Fahad Hospital of the University, Al-Khobar, and the Medical University of
      Hannover, in the spring of 2003. Naxos disease has been encountered in a 2-year
      old girl and her 30-year-old aunt of a Saudi Arab family. Deoxyribonucleic acid
      samples of this family were analyzed by polymerase chain-reaction (PCR)
      amplification of the respective region of the plakoglobin gene, and direct
      nucleotide sequencing of the PCR-products. Segregation analysis was performed
      employing the newly detected IVS11+22G/A polymorphism. RESULTS: Molecular genetic
      analysis of the DNA sample of the child diagnosed with Naxos disease showed
      absence of the Pk2157del2 mutation. In addition, the segregation analysis
      revealed heterozygosity for IVS11+22G/A in the affected girl. CONCLUSION: Absence
      of the Pk2157del2 frameshift in the affected child proved that Naxos disease in
      this Saudi Arab family is not caused by the same mutation that was identified in
      the Greek families. Furthermore, heterozygosity for the IVS11+22G/A polymorphism
      provided evidence for exclusion of the plakoglobin gene in this consanguineous
      family.

PMID- 15494821
TI  - Cardiopulmonary exercise testing. An underutilized diagnostic tool in Saudi
      Arabia.
AB  - OBJECTIVE: To assess the use of cardiopulmonary exercise testing (CPET) in major
      hospitals and medical centers throughout the Kingdom of Saudi Arabia (KSA) and to
      seek information on the way CPET is conducted. METHODS: Self-reported
      questionnaires on the use of CPET were mailed during the fall of 2002 to 54 major
      public and private hospitals and medical centers throughout the KSA. The response
      rate was 64.2%. The returned questionnaires were coded and data were analyzed.
      RESULTS: The findings indicated that more than 85% of the sample was not
      employing CPET in their medical centers. However, all of the surveyed centers
      were regularly performing stress electrocardiogram tests. Approximately 21% of
      those medical centers who did not have CPET are planning to have it in the near
      future. The most frequent reasons for not conducting CPET were lack of equipment,
      lack of trained technicians and lack of training in interpreting test results.
      Moreover, the most important reasons for conducting the CPET were pulmonary
      problems, followed by cardiac disorders. Treadmill and leg ergometer were used
      most as an exercise mode. Bruce protocol as well as institution specific
      protocols were equally used during CPET. Finally, there appears a lack of local
      cardiorespiratory data, especially for healthy Saudi females at all ages as well
      as older male group. CONCLUSION: Cardiopulmonary exercise testing as a diagnostic
      tool for cardiopulmonary diseases was extremely underutilized in Saudi hospitals
      and medical centers. Much greater efforts are needed to raise the awareness among
      physicians on the usefulness of CPET.

PMID- 15494822
TI  - Flexible fiberoptic bronchoscopy. Diagnostic yield.
AB  - OBJECTIVE: Fiberoptic bronchoscopy is a minimally invasive procedure with a high
      diagnostic yield. The aim of this study was to document the usefulness of the
      procedure in the diagnosis of various respiratory disorders in a Middle East
      country. METHODS: Data on all bronchoscopies carried out in Chest Diseases
      Hospital, Kuwait from January 1996 to December 1998 were retrospectively
      collected. RESULTS: Out of 968 cases, only 620 (64%) patients had a full follow
      up. Suspected pulmonary tuberculosis (TB) (51.6%), unresolving pneumonia (16.1%),
      hemoptysis with a normal chest radiograph (8.4%), lung mass (7.7%) and hilar
      lymphadenopathy (3.2%) were the most common indications. Eleven percent of
      patients who underwent bronchoscopy had a normal chest radiograph, the reason
      being hemoptysis in 75.4%, inhalation injury in 21.8% and suspected upper airway
      obstruction in 2.9%. In smear negative suspected TB cases, 22.5% proved to have
      active disease. Acid fast bacillus was identified in bronchoalveolar lavage,
      either by smear or culture, in 44 (73.3%) patients with suspected pulmonary TB
      and in 6 (54.5%) patients with miliary shadows. An underlying cause was
      identified in 28 (28%) patients with unresolving pneumonia. Ninety-four percent
      of cases with clinical impression of bronchogenic carcinoma could be diagnosed.
      Transbronchial biopsy was diagnostic in 79% patients with diffuse parenchymal
      lung disease. No complications other than transient hypoxemia and controllable
      bleeding were noticed. CONCLUSION: Generally, the indications for flexible
      fiberoptic bronchoscopy remained similar to elsewhere. Unlike western series, the
      majority of the cases were for the diagnosis of pulmonary infections especially
      TB.

PMID- 15494823
TI  - Use of nasal intermittent positive pressure ventilation to avoid intubation in
      neonates.
AB  - OBJECTIVE: Nasal intermittent positive pressure ventilation (NIPPV) has widely
      been used in neonates to prevent extubation failure and apnea. This pilot study
      was carried out to look at the early use of NIPPV to avoid intubation. METHODS:
      The study was carried out over a period of 3 months from August 2003 to October
      2003 at the Royal Hospital, Muscat, Sultanate of Oman. The neonates with clinical
      signs of moderate to severe respiratory distress were given a trial of early
      NIPPV based on the avoid-intubation protocol. Inclusion, exclusion and failure
      criteria with general procedure were made clear to all medical and nursing staff
      and the protocol was posted in the unit for further time to time referral.
      RESULTS: A total of 16 neonates met the inclusion criteria for early NIPPV trial.
      Out of these, 13 (81%) had a successful NIPPV. The mean age of entry was 0.95
      hours; however, the mean duration of NIPPV was 23 hours. No NIPPV related
      complications were noted in the study group. CONCLUSION: We concluded that NIPPV
      is an appropriate mode of ventilation in neonates requiring respiratory support.
      The major advantage of NIPPV is the non-invasive mechanics. It is also less
      expensive and less labor intensive. Further randomized controlled trials with
      larger sample size are warranted to confirm our findings.

PMID- 15494824
TI  - Multidrug resistant miliary tuberculosis and Pott's disease in an immunocompetent
      patient.
AB  - In a high tuberculosis TB prevalence country, mortality due to miliary TB is not
      unknown but the treatment outcome in general is good. We describe a previously
      healthy man with miliary TB who did not respond to 2-months antituberculous
      therapy with 4 drugs. Persistent complaints of backache, which antedated chest
      symptoms, resulted in a diagnosis of Pott's disease. Culture of bronchial
      aspirate yielded multidrug resistant Mycobacterium tuberculosis that responded
      slowly to streptomycin, ethionamide, cycloserine, clofazimine, ofloxacin,
      paraaminosalicylic acid and isoniazid. The association of multidrug resistant
      miliary TB with Pott's disease in an immunocompetent patient is yet to be
      highlighted.

PMID- 15494825
TI  - Thoracic actinomycosis presented with tracheoesophageal fistula and fatal
      pulmonary infection.
AB  - We report a case of a 60-year-old Saudi woman who developed tracheoesophageal
      fistula and fatal pulmonary infection secondary to thoracic actinomycosis. The
      cause, clinical presentation, radiological features and treatment of thoracic
      actinomycosis are discussed.

PMID- 15494826
TI  - Congenital alveolar proteinosis.
AB  - Pulmonary alveolar proteinosis is recently described as a rare cause of lung
      dysfunction and respiratory distress in term neonates. In several cases, a
      deficiency or insufficiency of surfactant protein B SP-B has been caused by a
      frame shift mutation in the gene encoding SP-B. Three siblings with congenital
      pulmonary alveolar proteinosis showed clinical and radiological evidence.
      Histopathological and immunohistochemical studies in the last sibling revealed
      deficiency of SP-B, one of the group of 3 specific lipoproteins that reduce the
      surface tension between air and liquid interface within pulmonary alveoli,
      suggesting a gene associated illness.

PMID- 15494827
TI  - An unusual presentation of primary amyloidosis.
AB  - A 65-year-old male patient presented with right upper-quadrant abdominal pain.
      Ultrasonography revealed hypoechoic lesion in the perihepatic and
      intraparenchymal area. Computed tomography (CT) showed hypodense lesion in the
      same localization. A fine needle biopsy specimen of the perihepatic lesion was
      hemorrhagic. On abdominal CT, the liver showed enhancement, but the spleen did
      not enhance. The spleen could not be detected by scintigraphic imaging using
      Tc99m sulfur dioxide. A diagnosis of primary amyloidosis was made by renal
      biopsy. Melphalan 10 mg/day for 4 days/month was started. The clinical and
      radiological follow up demonstrated a resorption of the hematoma. The patient is
      still alive at the eighth month of therapy.

PMID- 15494828
TI  - Abdominal cocoon. An unusual cause of intestinal obstruction.
AB  - We report a case of abdominal cocoon in a young male patient, presenting with
      acute intestinal obstruction and abdominal mass. This is a rare acquired
      condition of the peritoneum in which the small bowel is encased either partially
      or totally by a dense fibrous membrane. Operative findings, perioperative imaging
      and treatment guidelines are discussed. A better awareness of this condition may
      facilitate preoperative diagnosis; prevent inadvertent bowel damage at
      laparoscopy and unnecessary bowel resection at laparotomy.

PMID- 15494829
TI  - Salmonellosis and ulcerative colitis. A causal relationship or just a
      coincidence.
AB  - Coincidence of salmonellosis and ulcerative colitis is a rare clinical problem.
      Salmonella infection was reported to complicate the ulcerative colitis, as either
      facilitating its occurrence or activation. In this article, we present a case
      with salmonellosis whose clinicopathological findings also suggested ulcerative
      colitis. The patient improved rapidly after taking additional mesalazine to
      norfloxacin treatment. We conclude that salmonella infection might have either
      been coincidentally present or might have triggered an early ulcerative colitis
      in this patient who did not have history of inflammatory bowel diseases. In case
      of persistent severe diarrhea despite appropriate treatment, the possibility of a
      coincident inflammatory bowel disease such as ulcerative colitis should always be
      considered, especially in endemic regions for salmonellosis.

PMID- 15494830
TI  - Unusual location of eosinophilic granuloma.
AB  - Eosinophilic granuloma EG is a benign self-limiting disease, which belongs to the
      spectrum of Langerhans' cell histiocytosis LCH. The etiology of LCH remains
      unknown, although the evidence indicates that it is a clonal proliferative
      disorder of Langerhans cells, it has also been characterized as reactive
      disorder, neoplastic process and a berrant immune response. Eosinophilic
      granuloma is characterized by single or multiple skeletal lesions occurring
      predominately in children, adolescents and young adults, it accounts for 70% of
      LCH. It is more common in males, and the common sites are the skull, mandible,
      ribs, spines and long bones particularly the femur and the humerus. The estimated
      incidence of EG is 3-4 per million of the population. Vertebral bone involvement
      is rarely seen and usually affects the vertebral body. We are reporting an
      unusual case of EG in a female child presented with a solitary lesion at
      posterior element of lumbar vertebra.

PMID- 15494831
TI  - Uterine lipoma.
AB  - Pure lipoma of the uterus is a rare entity and few cases have been reported. They
      usually develop in postmenopausal women. Clinical symptoms and physical signs are
      similar to those found in leiomyomas. The histogenesis of these lesions is still
      unclear. The diagnosis is easily made at the time of surgery or at autopsy, but
      before this, they may lead to many problems in the differential diagnosis with
      another uterine tumors. Recent papers suggest the possibility of a preoperative
      diagnosis made by computed tomography and magnetic resonance imaging. We report a
      case of a 67-year-old postmenopausal women presented with pelvic pressure and
      urinary symptoms. Pathological evaluation revealed pure intramural lipoma of the
      uterus illustrating characteristic morphological and histological findings with
      no evidence of sarcomata's component.

PMID- 15494832
TI  - Congenital absence of gall bladder in a young Saudi medical student. Clinical,
      laboratory findings and analysis of body composition.

PMID- 15494833
TI  - Acquired pes cavus as a manifestation of limited joint mobility in type-1
      diabetes mellitus.

PMID- 15494834
TI  - Kidney transplant recipients and the incidence of adverse reactions to
      cyclosporin.

PMID- 15494835
TI  - A simplified bedside method for estimating glomerular filtration rate in term
      neonates.

PMID- 15494836
TI  - Anuric unless catheterized.

PMID- 15494837
TI  - A surviving baby born 24 weeks of gestational age and 490g weight without
      mechanic ventilation and surfactant replacement.

PMID- 15494838
TI  - Neonatal systemic candidiasis. A 14-year review.

PMID- 15494839
TI  - Neutropenia.

PMID- 15494840
TI  - Typhoid fever due to multiresistant Salmonella enterica serovar typhi having
      reduced susceptibility to ciprofloxacin and nalidixic acid resistance.

PMID- 15494841
TI  - Treatment of cutaneous leishmaniasis by intralesional metronidazole.

PMID- 15494842
TI  - Comparison of intravenous aminoglycoside therapy with switch therapy to cefixime
      in urinary tract infections.

PMID- 15494843
TI  - The services provided for combined oral contraceptive users in health care
      centers, Kerman, Iran.

PMID- 15494844
TI  - Safety of vaginal breech delivery.

PMID- 15494846
TI  - Effects of Ramadan fasting on cardiovascular diseases.

PMID- 15494845
TI  - Arteriovenous fistulas for hemodialysis. Patency rates and complications.

PMID- 15494847
TI  - Rheumatic valvular heart surgery and Maze III procedure.

PMID- 15494848
TI  - The outcome of non-operative treatment for undisplaced patellar fractures.

PMID- 15494849
TI  - Frequency of anemia in pregnancy in Northern Jordan.

PMID- 15494850
TI  - Specific chromosomal satellite association among infertile male patients.

PMID- 15494851
TI  - Hajj caravan 1423.

PMID- 15494852
TI  - Acetylator phenotype in Iraqi patients with discoid lupus erythematosus.

PMID- 15494853
TI  - Risk factors of coronary heart disease among Jordanians.

PMID- 15494854
TI  - Controversies in surgical pathology.

PMID- 15494855
TI  - Controversies in surgical pathology: minimal involvement of sentinel lymph node
      in breast carcinoma: prevailing concepts and challenging problems.
AB  - Sentinel lymph node biopsy has attained "standard of care'' status in the
      management of breast carcinoma. However, the pathological interpretation and
      clinical consequences of "minimally involved'' sentinel lymph nodes remain
      controversial. Herein, we present some of the complex and challenging
      pathological problems inherent in this evolving setting. Clearly, at least some
      of our current concepts regarding "minimally involved'' sentinel lymph nodes need
      reappraisal.

PMID- 15494856
TI  - An alternative viewpoint.

PMID- 15494857
TI  - Real-time PCR quantification of c-erbB-2 gene is an alternative for FISH in the
      clinical management of breast carcinoma patients.
AB  - Evaluation of gene amplification and protein expression of the c-erbB-2/neu in
      breast carcinomas has been an important task in breast cancer management.
      Although immunohistochemistry is widely applied, fluorescence in situ
      hybridization (FISH) technology shows its advantage in discriminating tumors in
      an objective manner. More recently, development of LightCycler technology permits
      evaluation of gene amplification with a small volume of DNA run in a 20 microL
      glass capillary. In this study, a series of 87 breast carcinomas were chosen for
      evaluation of c-erbB-2/neu gene amplification detected by both LightCycler
      technology and FISH. Real-time polymerase chain reaction (PCR) was performed in
      LightCycler capillaries with 10 ng sample DNA. By using LightCycler Relative
      Quantification Software version 1 (LightCycler, Roche, Mannheim, Germany), the
      amount of c-erbB-2 DNA was calculated as a ratio of c-erbB-2/reference gene
      quantity in a sample, and then the ratio was divided by the ratio of c-erbB-2
      gene/reference gene quantities of a calibrator DNA (a standard DNA provided in
      the kit), which was run with each sample reaction in parallel. Dual-color FISH
      was performed on sections of the formalin-fixed, paraffin-embedded tissue array
      samples using the DAKO HER2 FISH pharmDX kit (DAKO A/S, Glostrup, Danmark)
      according to the manufacturer's instructions. Furthermore, immunohistochemistry
      was performed in parallel, with both the NCL-CB11 and HercepTest antibodies. Both
      the FISH technology and the LightCycler-PCR identified a similar percentage of
      tumors with c-erbB-2 gene amplification in our present study, 16% (14/87) and 15%
      (13/87), respectively, whereas immunohistochemistry demonstrated 32% and 34% c
      erbB-2 overexpression with the NCL-CB11 and HercepTest antibodies, respectively.
      In addition, FISH and PCR were highly correlated in detecting tumors mainly with
      3+++ c-erbB-2 protein expression by immunohistochemistry, indicating that
      LightCycler real-time quantification of c-erbB-2 gene may be an alternative to
      FISH in breast cancer clinical application.

PMID- 15494858
TI  - Endometrial glandular dysplasia: a putative precursor lesion of uterine papillary
      serous carcinoma. Part II: molecular features.
AB  - Endometrial glandular dysplasia (EmGD) may be a newly defined precursor lesion of
      uterine papillary serous carcinoma (UPSC) by morphology. In this report, we
      studied molecular changes present in EmGD by the loss of heterozygosity (LOH)
      approach using laser capture microdissected tissue samples. Nineteen uteri
      showing at least 1 focus of EmGD by morphology were selected. These cases were 12
      UPSC, 2 clear cell carcinomas, 1 mixed uterine papillary serous and endometrioid
      carcinoma, 1 uterine carcinosarcoma, 1 serous endometrial intraepithelial
      carcinoma (EIC), and 2 EmGD involving endometrial polyps. Seven microsatellite
      polymorphic DNA markers (TP53 at 17p, D1S211, and D1S162 at 1p32, D17S1323 at
      17q21, D17S1330 at 17q25, D5S346 at 5q, and D2S123 at 2p) were utilized. A total
      of 123 laser-captured microdissection samples from 19 cases was studied with LOH
      method. The frequencies and patterns of LOH were analyzed and compared among
      benign resting endometrium (RE), EmGD, serous EIC, and UPSC. LOH was observed for
      at least 1 of the 7 markers in all categories of lesions, EmGD, serous EIC, and
      UPSC. The frequency of LOH for EmGD ranged from 4.2% to 31.3%; the range for
      serous EIC was 5.9% to 78.6%; and that for UPSC was 7.7% to 62.5%. The most
      frequent LOH in the 3 above-cited categories of lesions was identified at 17p
      (TP53) and 1p (D1S162). The frequency of LOH in EmGD with markers of TP53 and
      D1S162 was significantly higher than in RE (p < 0.05). With markers of D1S211 and
      D2S123, LOH in EmGD was higher than RE, approaching to a statistically
      significant level. Compared with foci of serous EIC and UPSC, however, the rate
      of LOH in EmGD was significantly lower only with TP53 locus (31.3% vs more than
      60%, p < 0.05). The difference of LOH frequency with other chromosomal markers
      between EmGD and serous EIC/UPSC did not reach a statistically significant level.
      A significantly high concordant LOH pattern was found between foci of EmGD and
      serous EIC/UPSC (p = 0.05). We conclude that EmGD frequently shows LOH at
      multiple chromosomal loci, particularly at 17p and 1p. Significantly high
      concordant LOH frequency between EmGD and paired serous EIC or UPSC strongly
      suggests that EmGD is a noncancerous precursor lesion of UPSC, probably also of
      serous EIC. The clinical significance of EmGD needs further studies.

PMID- 15494859
TI  - Dermatofibroma-a critical evaluation.
AB  - Dermatofibromas are common cutaneous lesions. In most cases, they can be readily
      identified clinically and show a typical histology. In a small percentage of
      cases they show unusual clinical and more often histologic features that may
      cause differential diagnostic problems. In addition there are reactive fibrous
      lesions with neural or smooth muscle features that we speculate may represent
      dermatofibroma variants.

PMID- 15494860
TI  - Tumors of the breast showing dual differentiation: a review.

PMID- 15494861
TI  - Epithelial lesions associated with invasive penile squamous cell carcinoma: a
      pathologic study of 288 cases.
AB  - A heterogeneous spectrum of epithelial alterations and atypical lesions affect
      the squamous epithelium of penile mucosal anatomical compartments. Analogous to
      other genital sites, the terminology utilized to define the lesions is variable.
      The few pathologic studies of penile precancerous lesions are mostly related to
      carcinoma in situ and human papilloma virus (HPV), and the information on low
      grade atypical lesions is limited. The objective of this study was to
      comprehensively describe the morphologic features of all epithelial alterations,
      benign and atypical, low grade and high grade, associated with invasive squamous
      cell carcinoma of the penis and to investigate their relation with each other and
      with subtypes of invasive carcinoma. We also propose herein a simple and
      reproducible nomenclature for penile precancerous abnormalities until more
      biological, molecular, or epidemiologic information on the lesions is available.
      Two hundred and eighty-eight penectomy and circumcision specimens with invasive
      squamous cell carcinoma were pathologically evaluated. Carcinomas were classified
      as usual, verrucous, papillary not otherwise specified, warty (condylomatous),
      basaloid, and mixed. Associated lesions were classified as squamous hyperplasia
      and squamous intraepithelial lesions of low and high grade (LGSIL and HGSIL). In
      LGSIL, atypia was confined to the lower third, and in HGSIL, atypical cells
      affected at least two thirds of the squamous epithelium. Subtypes of SIL were
      squamous, warty, basaloid, warty-basaloid, and papillary. Squamous hyperplasia,
      the most common lesion, was found in 83% of the cases, followed by LGSIL (59%)
      and HGSIL (44%). In 62% of the cases more than 1 associated lesion was present
      per specimen. A sequence from squamous hyperplasia to low-grade to high-grade SIL
      was seen frequently. Squamous hyperplasia was more commonly associated with usual
      squamous, papillary, and verrucous than with warty and basaloid invasive
      carcinomas. LGSIL was associated with all types of squamous cell carcinoma but
      was rarely present adjacent to basaloid or verrucous tumors. HGSIL was present in
      two thirds of invasive warty, basaloid, and mixed warty-basaloid tumors, in about
      half of usual squamous cell carcinomas, and was absent in papillary and verrucous
      carcinomas. Correlation of special types of invasive carcinomas with subtypes of
      SIL revealed morphologic correspondence of invasive tumor and the associated
      intraepithelial lesion. Squamous LGSIL was preferentially associated with
      verrucous, papillary, and usual squamous cell carcinomas; warty LGSIL, with
      invasive warty and mixed warty-basaloid carcinomas. High-grade SIL of the
      squamous type was frequently found in squamous cell carcinoma of usual type but
      was rarely present with warty or basaloid carcinomas. Basaloid HGSIL was
      associated with basaloid carcinoma, and HGSIL of warty type, with either warty or
      mixed warty-basaloid carcinomas. The high frequency of squamous hyperplasia and
      LGSIL and preferential association with usual, verrucous, and papillary
      carcinomas plus the subtle morphologic differences of the 2 lesions suggest that,
      despite its benign appearance, squamous hyperplasia is a precursor of the
      aforementioned carcinomas. The association and histologic similarities between
      high-grade SIL of the basaloid, warty, or mixed forms with their invasive
      counterparts indicate these lesions are their likely precursors.

PMID- 15494862
TI  - Reactive nodular fibrous pseudotumors of the gastrointestinal tract: report of 8
      cases.
AB  - Eight cases of reactive nodular fibrous pseudotumor of the gastrointestinal tract
      are presented. The patients included 6 males and 2 females between the ages of 1
      and 68 years (mean age 41.5 years). Three tumors involved the small intestine,
      and 5 of the investigated lesions were located in the large bowel. Of these, 2
      originated in the sigmoid colon, 1 in the cecum, 1 in the appendix, and 1 in the
      large bowel not otherwise specified. The tumors' size varied from 3 to 10 cm in
      the greatest diameter (mean 6.2 cm). Histologically they were composed of
      stellate or spindle shaped cells resembling fibroblasts arranged haphazardly or
      in intersecting fascicles, embedded in a collagen-rich stroma, with sparse
      intralesional mononuclear cells frequently arranged in lymphoid aggregates.
      Immunohistochemically, the lesions were positive for vimentin (7/7), smooth
      muscle actin (8/8), muscle-specific actin (5/7), cytokeratins AE1/AE3 (6/7), and
      CAM 5.2 (1/7), and antigen CD68 (1/7). No case (0/8) reacted positively with
      antibody to CD117 (c-kit). Genetically no substitutions, deletions, or insertions
      occurred in exon 11 in all analyzed samples. Likewise, no deletions or insertions
      in part of exon 9 were observed. Ultrastructurally the tumor cells revealed
      features typical of myofibroblasts. According to the morphologic,
      immunohistochemical, and ultrastructural features mentioned above, especially to
      the positivity of low-molecular-weight cytokeratins, we propose this lesion to be
      related to a proliferation of multipotential subserosal cells rather than
      ordinary myofibroblasts or fibroblasts.

PMID- 15494863
TI  - Nasal NK/T cell lymphoma in Taiwan: a clinicopathologic study of 22 cases, with
      analysis of histologic subtypes, Epstein-Barr virus LMP-1 gene association, and
      treatment modalities.
AB  - Nasal NK/T cell lymphoma is a distinctive type of extranodal lymphoma with an
      unique immunophenotype and a strong association with Epstein-Barr virus (EBV). It
      is one of the common extranodal lymphomas in Taiwan. We studied 22 cases of nasal
      NK/T cell lymphoma to characterize their clinicopathologic features and to
      explore the possible differences between histologic subtypes and their clinical
      behavior as well as the prevalence of 30-base pair (bp) deleted latent membrane
      protein-1 (LMP-1) gene of the EBV. They consisted of 5 cases of small cell type
      (SC), 6 cases of medium-sized cell type (MC), 6 cases of large cell type (LC),
      and 5 cases of pleomorphic cell type (PC). Twelve patients were men and 10 were
      women (1.2 to 1), and their ages ranged from 34 to 75 years with a median age of
      55.5 years. The median ages of the LC type and PC type were older than the other
      2 types. No other clinical features differed significantly among the 4 subtypes.
      Nasal obstruction was the most common initial presenting symptom. All but 1 case
      had stage IE disease at the time of diagnosis. Five cases developed extranasal
      involvement and skin was the most common site. No bone marrow involvement was
      detected. The majority of patients received local radiotherapy and chemotherapy.
      Local irradiation was more effective than chemotherapy alone. We achieved an
      overall survival of 63.6% at 5 years as estimated by the Kaplan-Meier analysis,
      which was better than other series. All cases displayed an immunophenotypic
      profile of CD3(epsilon)+, CD20-, CD56+, and TIA-1+ except that 1 case was
      CD3(epsilon)-. Fourteen of 22 cases (64%) expressed LMP-1. Nine cases of various
      cell types (41%) were also CD30+. Among the 4 histologic subtypes, the SC type
      differed from the other types by the absence of angiodestruction and necrosis,
      although angioinvasive growth was seen in 2 of them. Pseudoepitheliomatous
      hyperplasia was seen in only 3 cases of the SC type, and all 5 cases of the SC
      type were CD30-. No statistical difference in survival was found among the 4
      histologic subtypes or between CD30+ and CD30- cases. All 22 cases were positive
      for EBV by polymerase chain reaction and Epstein-Barr virus early RNA (EBER) in
      situ hybridization. A high prevalence rate of 86% (19/22) of the 30-base pair
      (bp) deleted LMP-1 gene was found, but 81.5% (22/27) of the EBV-positive control
      reactive lymphoid tissues also had the 30-bp deleted LMP-1 gene. Therefore, the
      high prevalence of the 30-bp deleted LMP-1 gene found in NK/T cell lymphoma could
      be due to the high prevalence of the deleted variant in this geographic region.
      However, it remains possible that the high prevalence of the deleted LMP-1 gene
      contributed to the increased incidence of EBV-associated nasal NK/T cell lymphoma
      in Taiwan.

PMID- 15494864
TI  - Kuttner's tumor of salivary glands resembling marginal zone B-cell lymphoma of
      the MALT type: a histopathologic and immunohistochemical study of 7 cases.
AB  - Kuttner's tumor is a benign inflammatory process of the submandibular gland that
      presents as a hard mass mimicking a malignant neoplasm clinically. The histologic
      feature varies according to stage of evolution and severity of inflammation. We
      report here 7 cases of Kuttner's tumor that morphologically resemble primary
      salivary gland marginal zone B-cell lymphoma of the mucosa-associated lymphoid
      tissue (MALT) type. Histologically, the lobular architecture was distorted and
      the septa showed sclerosis. There was a dense lymphoplasmacytoid infiltration
      with lymphoid follicle formation accompanied by loss of acini and ducts. In 4
      cases, a few salivary gland ducts contained the lymphoid cells within the
      epithelium. However, a true lymphoepithelial lesion was observed in none of the 7
      cases. Immunohistochemical study demonstrated a disrupted follicular dendritic
      cell network, which is a characteristic finding of follicular colonization of
      MALT-type lymphoma. In 6 cases, there were a few small foci of lymphocytes
      somewhat resembling centrocyte-like cells of MALT-type lymphoma. However,
      immunohistological study demonstrated the mixed nature of the cells resembling
      centrocyte-like cells. Moreover, the polytypic nature of B lymphocytes was
      demonstrated by immunohistochemistry and polymerase chain reaction.

PMID- 15494865
TI  - KI-67 antigen expression predicts survival and correlates with histologic subtype
      in the WHO classification of thymic epithelial tumors.
AB  - We performed an immunohistochemical study with monoclonal antibodies to Ki-67
      antigen and p53 protein on 45 cases of thymic epithelial tumors classified
      according to the recent World Health Organization (WHO) classification system to
      evaluate whether there is correlation between the expression of these markers and
      prognosis, histologic subtype, and myasthenia gravis (MG). We also correlated
      histologic subtype with sex, age, MG, and survival. Ki-67 and p53 labeling
      indices (LIs) were expressed as a percentage of positive nuclear immunostaining
      by counting 1,000 epithelial tumor cells. Statistically significant differences
      were found between Ki-67 LI and survival (p = 0.007), whereas the prognostic
      implication of p53 could not be demonstrated, although there appeared a trend
      that patients with tumors of higher LIs had worse survival. Significant
      correlations were also found between Ki-67 (p < 0.0005) and p53 (p < 0.0005) LIs
      and histologic subtypes. No correlation was found between these parameters and
      MG. Histologic subtypes of the WHO classification also correlated with survival
      (p = 0.01), whereas no correlation was found with sex, age, and MG. In
      conclusion, our results indicate that the proliferative activity, assessed by Ki
      67 LI, and the histologic pattern, according to WHO classification system, seems
      to represent reliable parameters in the prognosis of thymic epithelial tumors.

PMID- 15494866
TI  - The world's smallest adult rhabdomyoma.

PMID- 15494867
TI  - A nice squamoid kitten.

PMID- 15494868
TI  - Peripheral lymphadenopathy as the initial manifestation of pericardial
      mesothelioma: a case report.
AB  - Lymphadenopathy is an unusual initial presentation of malignant mesothelioma. We
      describe a case of extrathoracic lymphadenopathy as the only initial
      manifestation of primary pericardial malignant mesothelioma. The diagnosis of
      metastatic malignant mesothelioma was made by excisional biopsy of the
      supraclavicular lymph node and later confirmed by cytologic examination of
      pericardial fluid. The clinical and pathological features of this case, including
      positron-emission tomography (PET), immunohistochemistry, and electron
      microscopy, are discussed.

PMID- 15494869
TI  - Heterotopic mesenteric ossification ("intraabdominal myositis ossificans''): a
      case report.
AB  - Heterotopic ossification has been reported only rarely within the abdominal
      cavity, specifically in a mesenteric location (heterotopic mesenteric
      ossification). We describe the case of a 76-year-old man with no history of
      previous surgery who developed small bowel obstruction associated with multiple
      foci of heterotopic bone formation within the small bowel mesentery. He underwent
      small bowel and mesentery resection and is disease-free 9 months later.

PMID- 15494870
TI  - Glomus tumor of the duodenum: a case report.
AB  - We describe a rare case of glomus tumor of the duodenum. The tumor was detected
      in a 46-year-old man being investigated for episodes of gastrointestinal
      bleeding. The excised specimen showed a 2.3 x 1.5 x 1.5 cm gray-tan tumor
      involving the mucosa and the submucosa. The overlying mucosa was focally
      ulcerated. Histologically, the tumor had a solid pattern of sharply demarcated,
      round glomus cells with prominent pericytoma-like vessels of varying sizes. The
      neoplastic cells stained for vimentin, smooth muscle actin, and focally for
      synaptophysin. These histologic and immunohistochemical features are consistent
      with a diagnosis of glomus tumor of the duodenum.

PMID- 15494871
TI  - Gastric metaplasia and small bowel ulcerogenesis in a case of ulcerative
      jejunitis not related to celiac disease.
AB  - The possible relationship between gastric metaplasia and ulcerative lesions in an
      unusual case of ulcerative jejunitis not related to celiac disease and with
      extensive gastric metaplasia is discussed. Previous studies have described
      gastric metaplasia in duodenal ulcers on the basis of endoscopic data, and some
      authors maintain that acid secretion in metaplastic mucosa could represent a
      pathogenetic factor of ulcerogenesis, with a self-amplifying mechanism. In the
      absence of functional evidence, we could provide data, in a case of ulcerative
      jejunitis, about morphologic signs of acid secretion in gastric metaplastic
      epithelium using an antibody against HMFG-1, a good marker of acid-secreting
      fundic cells. Metaplastic areas demonstrated a focal positivity for HMFG-1, and
      these finding are suggestive of local acid secretion.

PMID- 15494872
TI  - Renal oncocytic angiomyolipoma.

PMID- 15494874
TI  - Hyperammonemia, bane of the brain.
AB  - Ammonia, normally produced from catabolism of amino acids, is a deadly
      neurotoxin. As such, the concentration of free ammonia in the blood is very
      tightly regulated and is exceeded by two orders of magnitude by its physiologic
      derivative, urea. The normal capacity for urea production far exceeds the rate of
      free ammonia production by protein catabolism under normal circumstances, such
      that any increase in free blood ammonia concentration is a reflection of either
      biochemical or pharmacologic impairment of urea cycle function or fairly
      extensive hepatic damage. Clinical signs of hyperammonemia occur at
      concentrations > 60 micromol/L and include anorexia, irritability, lethargy,
      vomiting, somnolence, disorientation, asterixis, cerebral edema, coma, and death;
      appearance of these findings is generally proportional to free ammonia
      concentration, is progressive, and is independent of the primary etiology. Causes
      of hyperammonemia include genetic defects in the urea cycle ("primary") or
      organic acidemias ("secondary"), as well as genetic or acquired disorders
      resulting in significant hepatic dysfunction. Thus, because of the neurotoxic
      implications of hyperammonemia and the typical absence of other specific
      laboratory abnormalities, appearance of the clinical signs should trigger an
      emergent search for elevated blood ammonia concentration.

PMID- 15494875
TI  - Idiopathic thrombocytopenic purpura: a 10-year natural history study at the
      childrens hospital of alabama.
AB  - Childhood idiopathic thrombocytopenic purpura (ITP) is a common disorder.
      However, single-institution, long-term, natural history data are limited. The
      objective of this paper is to review presenting features, response to therapy,
      and natural history of ITP treated at a single pediatric academic medical center.
      A retrospective chart review was made for all children (ages birth-18 years)
      diagnosed with ITP (ICD 287.3) and treated at the Childrens Hospital of
      Alabama/University of Alabama at Birmingham between 1993 and 2003. Four hundred
      nine patients were identified (49% male, 51% female; mean age: 5.85 years; range:
      1 month-17 years). There was no seasonal variation of presentation. The mean
      platelet count was 19k (0-120k). Bone marrow aspiration (BMA) was performed in
      72% but altered the diagnosis or therapy in no patient. Treatment consisted of
      corticosteroids in 256 (92% response), intravenous immunoglobulin (IVIG) in 125
      (87% response), Win-Rho D in 58 (91% response), and no therapy in 71 (100%
      response). Response was defined as increase in platelet count to > 50k. There was
      no difference in response to any therapy. No patients died. One patient presented
      with a CNS hemorrhage at presentation, responded to therapy, and survived. Twenty
      three of 409 patients (6%) experienced clinical bleeding requiring
      hospitalization or blood transfusion. Chronic ITP (persistence > 6 months) was
      noted in 99 patients (24%). Chronic patients presented at an older age (7.8 vs
      5.2 years for acute only, p<0.001), and with higher platelet counts (27k vs 17k,
      p<0.001). The risk of chronic ITP was partially predicted by presenting platelet
      count > 50k and age > 10 years, or both; 50% of patients presenting with these
      features developed chronic ITP vs 24% overall rate. Splenectomy was curative in
      30/31 (97%) patients. There was no postsplenectomy sepsis. Of 99 patients with
      chronic ITP, 25 responded to splenectomy, 37 resolved at a mean of 20.3 months
      after diagnosis (7-96 months), 36 had persistent mild thrombocytopenia (50k
      125k), and 1 failed to respond to any treatment including splenectomy. Overall,
      91% of cases resolved with therapy or observation. ITP is a common pediatric
      disease presenting at any age with low morbidity and mortality. Most cases can be
      managed by pediatricians without hematology referral. Several equally successful
      therapeutic options exist. Chronic cases present at an older age with higher
      platelet counts. Up to 50% of cases of chronic ITP will resolve with ongoing
      follow-up. The overall prognosis in childhood ITP is excellent.

PMID- 15494876
TI  - Preparing residents to counsel about smoking.
AB  - The objective of this study was to evaluate the effects of an innovative,
      multicomponent, theory-based educational intervention for pediatric residents on
      prevention of tobacco use counseling for cessation. Before and 3 months after
      intervention residents in a large urban midwestern pediatric residency program
      completed a self-assessment of measures of their attitudes and counseling
      behaviors. The intervention was a 3-hour multicomponent program including
      presentations, case discussions, role-plays and support material based on
      concepts from Motivational Interviewing (MI). Participants reported increased
      confidence in their ability to counsel, as well as greater frequency of
      counseling (standardized effect size (d) = 0.57). Residents also reported an
      increased use of principal components of MI, assessing how important quitting is
      to patients (d = .66), and how confident patients are in their ability to quit (d
      = .78). This brief educational intervention taught theory-based counseling
      techniques to pediatric residents. After the study, participants reported
      significant increases in their frequency of counseling as well as greater use of
      the MI principles.

PMID- 15494877
TI  - Factors associated with preventive asthma care in inner-city children.
AB  - The goal of this cross-sectional study was to determine if the caregiver's
      quality of life was associated with the child receiving appropriate preventive
      asthma care (2 or more preventive asthma care visits per year) in a sample of
      inner-city children with moderate to severe persistent asthma. Our findings
      confirm that children with moderate to severe persistent asthma are not receiving
      adequate preventive asthma care despite experiencing frequent asthma symptoms.
      Having a recent emergency department (ED) visit and increased number of school
      absences due to asthma were the strongest factors associated with these children
      receiving guideline-based preventive asthma care. However, for a subgroup of
      children without recent ED care, we found that low caregiver education level,
      increased school absences, and decreased caregiver's quality of life, albeit a
      trend, were associated with the child's receiving adequate preventive asthma
      care. This suggests that in a subgroup of children receiving adequate preventive
      care, other issues beyond basic asthma management may need to be addressed.

PMID- 15494878
TI  - Perceived barriers to healthcare: a survey of clients of the county board of
      mental retardation and developmental disabilities in cuyahoga county.

PMID- 15494880
TI  - Student evaluation practices in pediatric clerkships: a survey of the medical
      schools in the United States and Canada.
AB  - Despite the curriculum changes during the past decade, there is paucity of
      information regarding the structure and evaluation processes in pediatric
      clerkships. Information regarding the educational components of the pediatric
      clerkship and student evaluation practices was obtained from the pediatric
      clerkship directors via a paper/electronic survey. Completed surveys were
      received from 97 US and Canadian medical schools and were analyzed. The average
      length of a clerkship was 7 weeks. Most clerkships required a 4-week ward, a 1
      week newborn rotation, and a 2-week ambulatory rotation. Students were evaluated
      on each component of the clerkship in 93.5% of the programs. All programs
      evaluated student's clinical performance and fund of knowledge; 85.6% evaluated
      student's written record. Student's clinical performance was evaluated by direct
      observation in 57% of the programs. Penalties for failing in clinical performance
      were harsher. In 56% of programs, a student failing in clinical performance
      failed the entire clerkship in contrast to 21.8% or 7% of the programs where a
      student failed the entire clerkship if they failed in the examination for the
      fund of knowledge or written record evaluation, respectively. The survey
      demonstrated a fair amount of consistency in clerkships across programs when
      compared with data obtained in 1981 and 1986. There was a noticeable increase in
      the well-baby nursery rotation; however, there was a decline in direct
      observation to assess physical examination or clinical performance.

PMID- 15494879
TI  - Diagnostic yield of parathyroid hormone testing in children evaluated for
      hypercalciuria.
AB  - Hypercalciuria is a frequent cause of non-glomerular hematuria in pediatric
      patients. Because hypercalciuria can be secondary to primary hyperparathyroidism,
      measurement of serum parathyroid hormone (PTH) levels is often performed in
      children with this urinary abnormality. A retrospective chart review was
      performed to determine the diagnostic yield of PTH measurements when performed
      under these clinical circumstances. Over a 30-month period (January 1, 2001 to
      September 30, 2003), among 31 children who had a PTH determination, the level was
      elevated in 1 (3%) patient. Based on these findings and the serious nature of
      untreated primary hyperparathyroidism, serum PTH level should be measured in
      pediatric patients with newly diagnosed hypercalciuria.

PMID- 15494881
TI  - Physicians' attitude toward identification and management of childhood obesity in
      Israel.
AB  - Obesity is a serious health problem, and is becoming increasingly common in
      affluent societies. In 1998, an Expert Committee published guidelines regarding
      obesity evaluation and treatment. The purpose of this study was to assess the
      attitude of primary care physicians in Israel toward diagnosis and treatment of
      childhood obesity, as related to the recommended guidelines. Primary physicians
      caring for children and adolescents were asked to complete an anonymous
      questionnaire including personal and professional details, methods of diagnosis,
      documentation and treatment of childhood obesity, and familiarity with and
      implementation of the Expert Committee recommendations. One hundred forty-four
      physicians, treating approximately 100,000 children monthly, completed the
      questionnaire. Ninety-four percent were considered to have diagnosed obesity
      properly. Furthermore, only 19% reported weighing all children examined, while
      99% of the physicians suggested some treatment for obesity. The most frequent
      recommendations for managing obesity were referral to a dietitian (92%), physical
      exercise (85%), and group treatment (27%). The majority of physicians (78%) were
      not familiar with the new Expert Committee recommendations regarding obesity
      treatment. This study suggests that the majority of primary physicians diagnose
      obesity properly and recommend accepted modalities to manage obesity. A
      comprehensive program to prevent and treat obesity is recommended to improve the
      health status of the population.

PMID- 15494882
TI  - Healthy Steps: resident's perceptions.
AB  - The objective of this study is to determine pediatric residents' perception of
      Healthy Steps for Young Children, Healthy Steps Iowa, and Healthy Steps
      specialists. Twenty-nine of 37 (78%) pediatric residents participated in this
      survey. The Healthy Steps specialists facilitated pediatric residents' learning
      of anticipatory guidance (69%), and assured the patients received information
      efficiently (69%). Sixty-two percent reported that the Healthy Steps specialists
      did not interfere with their relationship as the patient's primary care provider.
      Seventy-six percent would consider using Healthy Steps specialists in their
      future practice. Program improvement areas include improving clinic efficiency
      with the incorporation of Healthy Steps specialists; increasing the pediatric
      residents' awareness of family violence, mental illness, and substance abuse; and
      improving their method of referral to community contacts.

PMID- 15494883
TI  - Factors affecting missed appointment rates for pediatric patients insured by
      medicaid in a traditional hospital-based resident clinic and hospital-owned
      practice settings.
AB  - Missed appointment rates (MAR) of pediatric patients insured by Medicaid and seen
      in a traditional hospital-based continuity (teaching) clinic were compared to the
      rates for the same patients after their care had been transitioned to a community
      practice. The hypothesis is that when rewarded with shorter waiting times, a less
      chaotic environment, and more pediatrician continuity, the MAR for patients
      insured by Medicaid would be lower in the practice setting than it had been in
      continuity clinic. The MAR decreased from 33% in the continuity clinic in 1999 to
      18% in the community practice in 2001 (p<0.01). It was also hypothesized that the
      MAR for patients insured by Medicaid would be higher in practices with a higher
      percentage of Medicaid appointments. Among 15 hospital-owned pediatric practices,
      the MAR for patients insured by Medicaid was positively correlated with the
      percentage of total appointments that were made by patients insured by Medicaid
      (correlation coefficient 0.706 [p<0.01]).

PMID- 15494884
TI  - Influence of breast-feeding and parental intelligence on cognitive development in
      the 24-month-old child.
AB  - This study was designed to analyze the relationship between breast-feeding and
      mental development at 24 months of age, independently of the influence of other
      factors. A total of 238 babies born between October 1995 and February 1998 were
      enrolled in an observational prospective cohort study. Cognitive development was
      assessed using the Bayley Infant Development Scale. The results of multiple
      linear regression analysis showed that infants breast-fed for longer than 4
      months scored 4.3 points higher on the mental development scale than those breast
      fed for less time. No differences were found in psychomotor development as a
      function of feeding regimen or duration. The positive linear correlation observed
      between parental IQ and mental development scores at 24 months was also
      statistically significant (mother: r = 0.39; p < 0.001; father: r = 0.43; p <
      0.001). It may be concluded that breast-feeding for longer than 4 months has a
      positive effect on the child's mental development at 24 months of age. Parental
      intelligence also appears to influence cognitive development.

PMID- 15494885
TI  - Changes in newborn bathing practices may increase the risk for omphalitis.
AB  - Aseptic cord care, in conjunction with antibacterial skin care, has reduced the
      incidence of omphalitis specifically caused by Staphylococcus aureus. However,
      this practice has resulted in the emergence of resistant organisms that may pose
      a greater risk for newborn infections. Subsequently, many institutions have
      changed to dry cord care and nonantiseptic whole-body baths, a practice that has
      not been adequately studied to determine potential infectious risks. Three cases
      of omphalitis occurring after an institutional change to nonantiseptic whole-body
      baths are presented. Clinical diagnosis and treatment of omphalitis are reviewed.
      Recommendations for surveillance of omphalitis are offered.

PMID- 15494886
TI  - CSF leakage after diagnostic lumbar puncture: case reports.

PMID- 15494887
TI  - Delayed diagnosis of penicillin-resistant Streptococcus mitis endocarditis
      following single-dose amoxicillin prophylaxis in a child.

PMID- 15494888
TI  - [Medicine has lost a great man: the death of Thure von Uexkull].

PMID- 15494889
TI  - [Validation of a screening instrument for multiple chemical sensitivity (MCS):
      the chemical odor sensitivity scale (COSS)].
AB  - Multiple Chemical Sensitivity (MCS) -- also known as Idiopathic Environmental
      Intolerances (IEI) -- is defined as a disorder with multiple somatic and
      psychological symptoms attributed to low levels of various, chemically unrelated
      substances in the environment. Self-reported chemical odor sensitivity is an
      important feature of MCS. We describe the construction and the reliability and
      validity properties of a short questionnaire for the assessment of chemical odor
      sensitivity (COSS). The 11 items of the COSS were factor analytically derived
      from the Questionnaire of Chemical and General Environmental Sensitivity (CGES).
      Test statistical properties of the COSS were examined in college students,
      unselected community members, environmental medicine outpatients and chemically
      sensitive subjects. The COSS achieved good internal consistency in all samples
      (Cronbach's alpha = 0.89 - 0.93). Women and subjects from samples with higher MCS
      risk showed elevated COSS scores. The scale showed adequate construct validity
      and proved useful as an economic screening instrument for persons at risk for
      MCS.

PMID- 15494890
TI  - [Psychometric properties and initial validation of the questionnaire on
      differentiated assessment of addiction].
AB  - The "Questionnaire on Differentiated Assessment of Addiction (QDAA)" is a multi
      modal, selfrating instrument for the Assessment of addiction and abuse of
      psychotropic substances. The QDAA provides the diagnosis of addiction as well as
      an overview of relevant information needed for the treatment of addiction.
      Several subscales assess variables that contribute to the development and
      maintenance of addiction such as mood, stress, expectancy of drug effects, self
      esteem, life satisfaction and coping ability. In the present study validity and
      reliability of the QDAA was tested in several dependent and non-dependent
      samples. A total of 575 non-dependent, alcohol-, heroin- and cannabis-dependent
      subjects was available for the present study. Six criteria (craving, tolerance,
      withdrawal, loss of control, addictive behavior, negative consequences), that
      form the basis of the addiction diagnosis were shown to have high internal
      consistency and can be reduced to one dimension by factor analysis. The resulting
      diagnosis of addiction is significantly correlated with the external criterion
      "dependence syndrome" of the ICD-10 by external experts. The assumed structure of
      the QDAA-subscales could be confirmed by factor analysis. In addition, the
      results of the subscale analysis provide empirical evidence for convergent
      validity. All subscales showed moderate to high internal consistency. The results
      suggest that the QDAA is a valid and reliable instrument for the differential
      assessment of substance addiction, abuse as well as relevant information in the
      context of addiction and its treatment.

PMID- 15494891
TI  - [Evaluation of the German Type D Scale (DS14) and prevalence of the Type D
      personality pattern in cardiological and psychosomatic patients and healthy
      subjects].
AB  - The Type D personality pattern, consisting of negative affectivity and social
      inhibition, has been shown by Denollet et al. to predict adverse prognosis in
      patients with coronary heart disease. For measuring the Type D characteristics,
      Denollet has devised the 14 item Type D scale (DS14). In the present study, this
      instrument was translated into German. The validity, reliability and adequacy of
      the German DS14 were then tested in 2421 persons, including cardiological and
      psychosomatic patients as well as healthy factory workers. The results document
      sound psychometric properties of the scale. Cronbach's alpha was 0.87 for the
      negative affectivity subscale and 0.86 for social inhibition. The two-factor
      structure of the original instrument could be clearly replicated. The prevalence
      rates of the Type D pattern were lowest in cardiological patients (25 %) and
      highest in psychosomatic patients (62 %). The prevalence in this German sample of
      cardiology patients was also lower than the one observed in healthy factory
      workers (32.5 %) and in CHD samples reported in the literature. These group
      differences could not be accounted for by differences in age and sex
      distribution. In conclusion, the DS14 is a valid and reliable instrument that can
      be used for an economic evaluation of the Type D characteristics in patients and
      healthy persons. The possible meaningfulness of the low Type D prevalence in
      cardiac patients and the prognostic relevance of this pattern require further
      study.

PMID- 15494892
TI  - [Psychosocial problems and coping strategies of young patients with cleft lip and
      palate].
AB  - OBJECTIVE: The purpose of this study was to improve the psychological care of
      young patients with cleft lip and palate by gaining insight into those
      problematic areas in which social conflicts arise and coping-strategies become
      necessary for the patients. METHODS: The procedure included semi-standardized
      interviews with 20 patients aged between 12 - 17 and their mothers. Every
      interview was recorded on tape, transcribed, analyzed contextually and
      categorized. RESULTS: Four areas of main problems showed up: the time of surgery,
      the experience of being rejected or teased by peers, remaining visible defects
      and how to integrate them into self-percept, the problems of the siblings. The
      mothers showed more pessimistic perceptions regarding the coping strategies of
      their children and the helpful role of parental support. Consequences for
      individual support and family therapy are derived.

PMID- 15494894
TI  - Recent developments in the management of herpes simplex virus infection in HIV
      infected persons.

PMID- 15494893
TI  - A second-generation genomic screen for multiple sclerosis.
AB  - Multiple sclerosis (MS) is a debilitating neuroimmunological and
      neurodegenerative disorder. Despite substantial evidence for polygenic
      inheritance of the disease, the major histocompatibility complex is the only
      region that clearly and consistently demonstrates linkage and association in MS
      studies. The goal of this study was to identify additional chromosomal regions
      that harbor susceptibility genes for MS. With a panel of 390 microsatellite
      markers genotyped in 245 U.S. and French multiplex families (456 affected
      relative pairs), this is the largest genomic screen for MS conducted to date.
      Four regions met both of our primary criteria for further interest (heterogeneity
      LOD [HLOD] and Z scores >2.0): 1q (HLOD=2.17; Z=3.38), 6p (HLOD=4.21; Z=2.26), 9q
      (HLOD; Z=2.71), and 16p (HLOD=2.64; Z=2.05). Two additional regions met only the
      Z score criterion: 3q (Z=2.39) and 5q (Z=2.17). Further examination of the data
      by country (United States vs. France) identified one additional region
      demonstrating suggestive linkage in the U.S. subset (18p [HLOD=2.39]) and two
      additional regions generating suggestive linkage in the French subset (1p
      [HLOD=2.08] and 22q [HLOD=2.06]). Examination of the data by human leukocyte
      antigen (HLA)-DR2 stratification identified four additional regions demonstrating
      suggestive linkage: 2q (HLOD=3.09 in the U.S. DR2- families), 6q (HLOD=3.10 in
      the French DR2- families), 13q (HLOD=2.32 in all DR2+ families and HLOD=2.17 in
      the U.S. DR2+ families), and 16q (HLOD=2.32 in all DR2+ families and HLOD=2.13 in
      the U.S. DR2+ families). These data suggest several regions that warrant further
      investigation in the search for MS susceptibility genes.

PMID- 15494895
TI  - Calculating the contribution of herpes simplex virus type 2 epidemics to
      increasing HIV incidence: treatment implications.
AB  - Herpes simplex virus type 2 (HSV-2) is the most prevalent sexually transmitted
      pathogen worldwide. There is considerable biological and epidemiological evidence
      that HSV-2 infection increases the risk of acquiring HIV infection and may also
      increase the risk of transmitting HIV. Here, we use a mathematical model to
      predict the effect of a high-prevalence HSV-2 epidemic on HIV incidence. Our
      results show that HSV-2 epidemics can more than double the peak HIV incidence;
      that the biological heterogeneity in susceptibility and transmission induced by
      an HSV-2 epidemic causes HIV incidence to rise, fall, and then rise again; and
      that HSV-2 epidemics concentrate HIV epidemics, creating a "core group" of HIV
      transmitters. Our modeling results imply that findings from HSV-2 intervention
      trials aimed at reduction of HIV incidence will be variable and that positive
      findings will be obtained only from trials in communities in which HIV incidence
      is steeply rising.

PMID- 15494896
TI  - Resistance of herpes simplex virus infections to nucleoside analogues in HIV
      infected patients.
AB  - Antiviral treatment of herpes simplex virus (HSV) infections with nucleoside
      analogues has been well established for >2 decades, but isolation of drug
      resistant HSV from immunocompetent patients has remained infrequent (0.1%-0.7% of
      isolates) during this period. Even when drug-resistant HSV is isolated from an
      immunocompetent patient, this virus, with rare exceptions, is cleared normally
      without adverse clinical outcome. Although drug-resistant HSV is more commonly
      isolated from immunocompromised patients (4%-7% of isolates) and is more likely
      to be clinically significant, the prevalence of drug-resistant HSV even among
      these patients, has been stable over the past 2 decades. Despite this stable
      prevalence, disease due to drug-resistant HSV remains an important problem for
      many immunocompromised patients, including those with HIV infection. This article
      reviews the prevalence, pathogenesis, and implications of drug-resistant HSV
      infections in HIV-infected patients.

PMID- 15494897
TI  - Efficacy and safety of valacyclovir for the suppression and episodic treatment of
      herpes simplex virus in patients with HIV.
AB  - Three randomized controlled trials of valacyclovir for the management of
      recurrences of genital herpes in HIV-infected persons were conducted between 1991
      and 2002. One study evaluated episodic therapy for the treatment of genital
      herpes, and 2 studies evaluated continuous suppressive therapy. Valacyclovir at
      1000 mg twice daily for 5 days was comparable to acyclovir at 200 mg 5 times
      daily in accelerating healing of a single episode of genital herpes (hazard
      ratio, 1.0; 95% confidence interval [CI], 0.8-1.2; P=.89). Valacyclovir at 500 mg
      twice daily was effective in preventing or delaying recurrences of genital herpes
      compared with placebo (hazard ratio, 0.20; 95% CI, 0.13-0.30; P<.001) and with
      valacyclovir at 1000 mg once daily (hazard ratio, 0.56; 95% CI, 0.40-0.80;
      P=.001), in 6-month and 48-week studies, respectively. The safety profile of
      valacyclovir was similar to that of acyclovir. Valacyclovir is well tolerated,
      safe, and effective for the treatment and suppression of recurrent genital herpes
      in human immunodeficiency virus-infected persons.

PMID- 15494898
TI  - HIV-associated thrombotic microangiopathy in the era of highly active
      antiretroviral therapy: an observational study.
AB  - The prevalence and predisposing factors of thrombotic microangiopathy (TMA) in
      the era of highly active antiretroviral therapy (HAART) were evaluated among
      patients in the Collaborations in Human Immunodeficiency Virus (HIV) Outcomes
      Research/US cohort. Of 6022 patients, 17 (0.3%) had TMA, with unadjusted
      incidences per 100 person-years of 0.079 for TMA, 0.009 for thrombotic
      thrombocytopenic purpura, and 0.069 for hemolytic-uremic syndrome. Compared with
      patients without TMA, patients with TMA had lower mean CD4(+) cell counts (197
      vs. 439 cells/mm(3); P=.0009) and higher mean log(10) HIV-1 RNA levels (4.6 vs.
      3.3 copies/mL; P=.0001) at last follow-up and a significantly greater incidence
      of acquired immune deficiency syndrome (82.4% vs. 55.3%; P=.025), Mycobacterium
      avium complex infection (17.6% vs. 3.3%; P=.018), hepatitis C (29.4% vs. 11.3%;
      P=.001), and death (41.2% vs. 7.4%; P<.0001). The prevalence of herpes and use of
      antiherpetics were slightly higher for patients with TMA, but unadjusted
      distributions were not statistically significant. TMA in a cohort surveyed after
      the introduction of HAART was rare and was associated with advanced HIV disease.

PMID- 15494899
TI  - Two patients with cryptococcal meningitis and idiopathic CD4 lymphopenia:
      defective cytokine production and reversal by recombinant interferon- gamma
      therapy.
AB  - BACKGROUND: Although Cryptococcus neoformans is a fungal pathogen that causes
      human disease predominantly in the immunocompromised host, severe cryptococcal
      infections are occasionally encountered in apparently immunocompetent
      individuals. Activation of cellular immunity by proinflammatory cytokines plays a
      central role in anticryptococcal defense. METHODS: We describe 2 patients with
      severe cryptococcal meningitis who appeared to have idiopathic CD4 lymphopenia.
      For these patients and for 4 healthy volunteers, ex vivo stimulation of whole
      blood with microbial stimuli was used to investigate putative defects in cytokine
      production capacity. RESULTS: Assessment of the cytokine released from the 2
      patients with CD4 lymphopenia revealed a defective production of the
      proinflammatory cytokines interferon (IFN)- gamma and tumor necrosis factor (TNF)
      but not of the anti-inflammatory cytokine interleukin-10 (IL-10). One patient
      with disease progression despite receipt of antifungal treatment was administered
      immunotherapy with recombinant IFN- gamma . Administration of recombinant IFN-
      gamma resulted in both restoration of immunological parameters and a sustained
      clinical recovery. CONCLUSIONS: Refractory meningitis may be due to defective TNF
      and IFN- gamma production, and IFN- gamma treatment may be useful in patients
      with an impaired cellular immune response and refractory cryptococcal meningitis.

PMID- 15494900
TI  - Cytomegalovirus retinitis in a patient treated with anti-tumor necrosis factor
      alpha antibody therapy for rheumatoid arthritis.
AB  - BACKGROUND: Anti-tumor necrosis factor alpha (anti-TNF- alpha ) antibodies have
      been used for the treatment of chronic inflammatory diseases such as rheumatoid
      arthritis (RA) and psoriasis arthritis. Such antibody therapies result in a
      severe interference with the patient's immune system. Increased rates of upper
      respiratory tract infection, reactivation of latent tuberculosis, and other
      systemic infectious diseases have been reported among patients receiving anti-TNF
      alpha antibodies. METHODS: As a note of caution, we describe a 57-year-old woman
      who received therapy with anti-TNF- alpha antibodies for RA refractory to
      methotrexate. After almost 2 years of treatment, she developed a severe
      cytomegalovirus (CMV) retinitis of the right eye. RESULTS: Laboratory assays
      revealed an immune status with nearly total loss of the cellular immune response
      and partial reduction of the humoral immune response. Intravenous treatment with
      ganciclovir, followed by oral administration of valganciclovir, resulted in an
      ophthalmological remission. Cessation of immunosuppressive therapy led to partial
      immunological reconstitution in the patient. Six months after discontinuation of
      immunosuppressive therapy, CMV retinitis of the left eye occurred but was treated
      successfully with a second course of oral valganciclovir. CONCLUSION: In the
      light of this first reported case of a serious CMV infection following therapy
      with anti-TNF- alpha antibodies, CMV infection should be considered in
      symptomatic patients.

PMID- 15494901
TI  - Mass antibiotic treatment and community protection in trachoma control programs.
AB  - Azithromycin is highly effective against trachoma, but the practical difficulties
      of community-wide distribution often leave many individuals untreated. We
      demonstrate, after mass azithromycin treatment of a population in Ethiopia, an
      indirect protective effect that occurred among untreated children who resided in
      villages in which most individuals had been treated. Similarities with the
      indirect protection within a treated community (i.e., "herd protection") that has
      been observed in vaccination programs are discussed.

PMID- 15494902
TI  - Disseminated pyogenic Mycoplasma pneumoniae infection in a renal transplant
      recipient, detected by broad-range polymerase chain reaction.
AB  - Although extrapulmonary manifestations of Mycoplasma pneumoniae infection are
      generally immune-mediated, disseminated infections occasionally occur. We
      describe a renal transplant recipient who developed disseminated pyogenic M.
      pneumoniae infection that was detected by broad-range polymerase chain reaction
      and that manifested by prosthetic arterial graft infection, psoas abscess, and
      septic arthritis.

PMID- 15494903
TI  - Practice guidelines for the management of bacterial meningitis.

PMID- 15494904
TI  - A randomized clinical trial to compare fleroxacin-rifampicin with flucloxacillin
      or vancomycin for the treatment of staphylococcal infection.
AB  - BACKGROUND: Oral combination therapy with fluoroquinolones plus rifampicin is a
      promising alternative to standard parenteral therapy for staphylococcal
      infections. METHODS: In a multicenter, randomized trial, we compared the
      efficacy, safety, and length of hospital stay for patients with staphylococcal
      infections treated either with an oral combination of a fluoroquinolone
      (fleroxacin) plus rifampicin or with standard parenteral treatment
      (flucloxacillin or vancomycin). Patients were included if cultures showed the
      presence of bacteremia or deep-seated infections with Staphylococcus aureus (104
      patients) or catheter-related bacteremia due to drug-susceptible, coagulase
      negative staphylococci (23 patients). RESULTS: The cure rate in the intention-to
      treat analysis was 78% for the fleroxacin-rifampicin group (68 patients) and 75%
      for the standard therapy group (59 patients; 47 received flucloxacillin, and 12
      received vancomycin); in the population of clinically evaluable patients (n=119),
      the cure rate was 82% and 80%, respectively; and in the population of
      microbiologically evaluable patients (n=103), the cure rate was 86% and 84%,
      respectively. Clinical and bacteriological failures after S. aureus infections
      were documented in similar proportions of patients. The median length of hospital
      stay after study entry was 12 days in the fleroxacin-rifampicin group, compared
      with 23 days in the standard treatment group (P=.006). More adverse events
      probably related to the study drug were reported in the fleroxacin-rifampicin
      group than in the standard therapy group (15 of 68 vs. 5 of 59 patients; P=.05).
      CONCLUSIONS: This study suggests that an oral regimen containing a
      fluoroquinolone plus rifampicin may be effective for treating staphylococcal
      infections, allowing earlier discharge from the hospital.

PMID- 15494905
TI  - The clinical impact of ganciclovir prophylaxis on the occurrence of bacteremia in
      orthotopic liver transplant recipients.
AB  - BACKGROUND: Cytomegalovirus (CMV) infection or receipt of a CMV-seropositive
      donor liver has been shown to be an independent predictor of bacteremia in
      orthotopic liver transplant (OLT) recipients. However, prevention of CMV
      infection through use of intense CMV prophylaxis has not been examined to assess
      the impact on bacteremia in liver transplant recipients. METHODS: We analyzed the
      impact of CMV prophylaxis on rates of bacteremia by examining 192 consecutive OLT
      recipients during a 2-year follow-up period. RESULTS: There were 29 episodes of
      bacteremia. Univariate analysis of risk factors for bacteremia showed that
      invasive fungal disease, initial anti-lymphocyte immunosuppression, treatment for
      rejection, and use of solumedrol were significantly associated with increased
      risk. Receipt of >or=14 days of ganciclovir prophylaxis (hazard ratio [HR], 0.40;
      95% CI [confidence interval], 0.18-0.87; P=.02), end-to-end biliary anastomosis,
      and receipt of <10 units of red blood cells (RBCs) were significantly associated
      with a decreased risk. Three-variable analysis controlling for end-to-end
      anastomosis and use of <10 units of RBCs, showed that use of >or=14 days of
      ganciclovir was still associated with a reduced risk of bacteremia (HR, 0.44; 95%
      CI, 0.20-0.98; P=.0437). CONCLUSIONS: Among factors associated with bacteremia,
      use of prophylactic ganciclovir is independently associated with a significant
      reduction of bacteremia in OLT recipients.

PMID- 15494906
TI  - Influenza infections after hematopoietic stem cell transplantation: risk factors,
      mortality, and the effect of antiviral therapy.
AB  - BACKGROUND: Community-acquired respiratory viruses, such as influenza virus, are
      thought to be major causes of morbidity and mortality in patients who had
      undergone hematopoietic stem cell transplantation (HSCT). Risk factors for
      acquisition, progression to pneumonia, and the effect of antiviral therapy are
      unknown. METHODS: We reviewed records from patients with documented influenza
      over 12 consecutive respiratory-virus infection seasons at a single
      transplantation center. RESULTS: From 1 September 1989 through 31 March 2002,
      influenza virus was isolated from 62 of 4797 persons undergoing HSCT (1.3%); 44
      patients had upper respiratory tract infections (URIs) alone, and 18 developed
      pneumonia. Among patients with influenza virus infection, pneumonia developed
      more commonly among those infected earlier after transplantation (median, 36 vs.
      61 days, P=.04) and those with concurrent lymphopenia. Of the 51 cases that were
      initially diagnosed as URIs, 17 were treated with antivirals, and 34 were not
      treated. Six untreated patients (18%) developed pneumonia, whereas 1 (13%) of 8
      patients treated with rimantadine and 0 of 9 treated with oseltamivir developed
      pneumonia. The duration of influenza virus shedding was longer in patients
      treated with steroid doses of >1 mg/kg than among those treated with doses of <1
      mg/kg (mean, 15 vs. 9 days); there was a trend towards decreased shedding with
      oseltamivir therapy (but not rimantadine therapy) after controlling for steroid
      use (P<.08). The 30-day mortality rate was highest among patients who had
      progression to pneumonia (5 [28%] of 18 patients); pulmonary copathogens (such as
      Aspergillus fumigatus) were commonly isolated. CONCLUSIONS: Influenza virus
      infection is an important cause of mortality early after HSCT. Our nonrandomized
      data suggest that early antiviral therapy with neuraminidase inhibitors may
      prevent progression to pneumonia and decrease viral shedding, which may prevent
      both influenza-related death in index patients and nosocomial transmission to
      others.

PMID- 15494907
TI  - Placebo-controlled, double-blind trial of intravenous ribavirin for the treatment
      of hantavirus cardiopulmonary syndrome in North America.
AB  - BACKGROUND. Ribavirin is active in vitro against hantaviruses, but the findings
      of an open trial of the use of intravenous ribavirin for the treatment of
      hantavirus cardiopulmonary syndrome (HCPS) were inconclusive. METHODS: Subjects
      with suspected HCPS in the prodrome or cardiopulmonary phase but without shock
      were eligible for randomization to receive either intravenous ribavirin (33 mg/kg
      [<or=2 g], followed by 16 mg/kg [<or=1 g] given every 6 h for 4 days and by 8
      mg/kg [<or=.5 g] given every 8 h for 3 days) or placebo (administered for 7 days
      or until the initial Sin Nombre virus antibody test result was confirmed to be
      negative). The primary outcome was survival at day 28 of the study without the
      need for extracorporeal membrane oxygenation (ECMO). RESULTS: Thirty-six subjects
      were enrolled in the trial from March 1996 through July 2001, at which point the
      study was terminated prematurely because of both the slow rate of accrual of
      subjects and the findings of a futility analysis. Of the 36 subjects enrolled, 23
      (all of whom were enrolled during the cardiopulmonary stage of HCPS) had HCPS
      confirmed by serologic testing. The severity of illness at entry into the study
      was similar among the 10 subjects with HCPS who received ribavirin and the 13
      subjects with HCPS who received placebo. The proportion of subjects who survived
      and who did not require ECMO was similar among ribavirin recipients and placebo
      recipients (70% vs. 62%, respectively); 2 ribavirin recipients and 2 placebo
      recipients died, including 3 of 7 subjects treated with ECMO. The frequency of
      adverse events, including anemia, was similar between treatment groups.
      CONCLUSIONS: The rate of accrual of subjects in the present study was inadequate
      to clearly assess the safety or efficacy of ribavirin in the treatment of HCPS.
      However, ribavirin was well tolerated, and the lack of trends supporting the use
      of intravenous ribavirin suggests that it is probably ineffective in the
      treatment of HCPS in the cardiopulmonary stage.

PMID- 15494908
TI  - The importance of bactericidal drugs: future directions in infectious disease.
AB  - BACKGROUND: Although a considerable amount of research has gone into the study of
      the role of bactericidal versus bacteriostatic antimicrobial agents in the
      treatment of different infectious diseases, there is no accepted standard of
      practice. METHODS: A panel of infectious diseases specialists reviewed the
      available literature to try to define specific recommendations for clinical
      practice. RESULTS: In infections of the central nervous system, the rapidity with
      which the organism is killed may be an important determinant, because of the
      serious damage that may occur during these clinical situations. The failure of
      bacteriostatic antibiotics to adequately treat endocarditis is well documented,
      both in human studies and in animal models. CONCLUSION: The bulk of the evidence
      supports the concept that, in treating endocarditis and meningitis, it is
      important to use antibacterial agents with in vitro bactericidal activity. This
      conclusion is based on both human and animal data. The data to support
      bactericidal drugs' superiority to bacteriostatic drugs do not exist for most
      other clinical situations, and animal models do not support this concept in some
      situations. Clinicians should be aware that drugs that are bacteriostatic for one
      organism may in fact be bactericidal for another organism or another strain of
      the same organism.

PMID- 15494909
TI  - The effect of initial drug resistance on treatment response and acquired drug
      resistance during standardized short-course chemotherapy for tuberculosis.
AB  - BACKGROUND: In Tomsk Oblast, Russian Federation, during the period of 1996-2000,
      most previously untreated patients with tuberculosis received standardized short
      course chemotherapy, irrespective of drug-susceptibility testing results. A
      retrospective analysis was done to determine the effect of initial drug
      resistance on treatment outcome and acquired drug resistance in new patients
      receiving standardized short-course chemotherapy. METHODS: During the period of 1
      November 1996 through 31 December 2000, a total of 2194 patients received a
      category 1 treatment regimen. Drug susceptibility test results for 1681 patients
      were available for analysis. Drug resistance patterns before and during treatment
      were compared for 73 patients whose culture results were persistently positive
      during treatment. Acquired resistance was defined as new drug resistance (during
      or at the end of treatment) that was not present at the beginning of treatment.
      RESULTS: Pretreatment drug resistance was strongly associated with treatment
      failure. In patients who had strains with pretreatment resistance patterns that
      included isoniazid or rifampin resistance, but not resistance to both, 17 (70.8%)
      of 24 cases involving treatment failures acquired new multidrug resistance. In
      patients with pretreatment pan-susceptible or streptomycin-monoresistant strains,
      13 (41.9%) of 31 cases involving treatment failures acquired new multidrug
      resistance. CONCLUSIONS: Early diagnosis of drug-resistant tuberculosis and
      judicious use of second-line drugs is recommended to decrease transmission of
      drug-resistant strains and to prevent the creation of multidrug-resistant
      strains. Finally, if drug susceptibility tests are not available or results are
      delayed, physicians should recognize that patients who do not respond to directly
      observed empirical short-course chemotherapy are at high risk of having multidrug
      resistant tuberculosis and should be treated accordingly.

PMID- 15494910
TI  - A comparative trial of a single dose of azithromycin versus doxycycline for the
      treatment of mild scrub typhus.
AB  - BACKGROUND: Scrub typhus is one of the most important endemic infections in the
      Asia-Pacific region. Although tetracyclines or chloramphenicol are the
      recommended drugs of choice for the treatment of scrub typhus, reports of
      doxycycline-resistant strains have prompted a search for alternative treatments.
      METHODS: We conducted a prospective, open-label, randomized trial from September
      2002 through November 2003 to compare azithromycin with doxycycline for the
      treatment of mild scrub typhus. The time to defervescence was assessed to compare
      the efficacy of the 2 treatment regimens. RESULTS: A total of 93 patients were
      randomly assigned to receive either a single 500-mg dose of azithromycin or a 1
      week course of daily oral 200-mg dose of doxycycline. Cure was achieved in 47
      (100%) of 47 patients in the azithromycin-treated group and in 43 (93.5%) of 46
      patients in the doxycycline-treated group (P=.117). The median time to
      defervescence was 21 h for the azithromycin-treated group and 29 h for the
      doxycycline-treated group (P=.097). There were no serious adverse events during
      the study. No relapses occurred in either group during a 1-month follow-up
      period. CONCLUSION: The single 500-mg dose of azithromycin was as effective as
      the 1-week course of daily 200-mg doses of doxycycline for the treatment of mild
      scrub typhus acquired in South Korea.

PMID- 15494911
TI  - Primaquine therapy for malaria.
AB  - Primaquine is the only available drug for preventing relapse of malaria, and
      confusion surrounds its use. This review examines the wide range of clinical
      applications of primaquine described in the medical literature between 1946 and
      2004. The risk of relapse of Plasmodium vivax malaria without primaquine therapy
      ranged from 5% to 80% or more, depending largely upon geographic location.
      Supervision of therapy profoundly impacts the risk of relapse, and almost all
      reports of malaria resistant to primaquine are associated with lack of such
      supervision. We nonetheless suspect that there is widespread resistance to the
      standard course of primaquine therapy, which is 15 mg primaquine base daily for
      14 days. Clinical evidence confirms that a course of 15 mg daily for just 5 days,
      a regimen widely used in areas where malaria is endemic, has no discernible
      efficacy. This review supports a recommendation for a regimen of 0.5 mg/kg
      primaquine daily for 14 days, on the basis of superior efficacy and good
      tolerability and safety in nonpregnant persons without glucose-6-phosphate
      dehydrogenase deficiency.

PMID- 15494912
TI  - The changing face of surveillance for health care-associated infections.
AB  - Surveillance of health care-associated infections and antimicrobial resistance is
      an important aspect of prevention. In 2004, the Centers for Disease Control and
      Prevention had 3 national health care surveillance systems. During 2004-2005,
      these will be combined into a single Internet-based system, the National
      Healthcare Safety Network (NHSN). The NHSN will feature a number of enhancements,
      and ultimately, all US hospitals and other health care facilities will be
      encouraged to participate. Health care surveillance using standard methods has
      been very useful and is cited as a model for prevention. However, alternative
      approaches may improve health care surveillance by reducing complexity,
      decreasing the burden of data collection, and improving accuracy. These
      alternative approaches include adopting simpler methods and more-objective
      definitions, using sampling and estimation, substituting information in computer
      databases for manually collected data, and increasing surveillance for process
      measures with known prevention efficacy. Maintaining successful features of
      standard systems, adopting alternate surveillance approaches, and exploiting new
      technologies, such as the Internet, will make health care surveillance an even
      better tool for prevention.

PMID- 15494913
TI  - Treatments for hepatitis B.
AB  - New optimism surrounds treatments for chronic hepatitis B (CHB). Interferon-
      alpha , lamivudine, and adefovir dipivoxil are currently approved by the United
      States Food and Drug Administration for the treatment of CHB. All 3 treatments
      possess unique characteristics with respect to their side effect profiles,
      potencies, and treatment niches within the spectrum of CHB. New agents, which are
      in various stages of clinical development, represent potential improvements
      within existing, as well as novel, classes of antiviral therapy, and they offer
      significant promise of a cure for the many patients with chronic and progressive
      hepatitis B. However, there remain many challenges in understanding the
      implications of drug resistance, the role of combination therapy, and how to
      define the response to therapy within subsets of patients with hepatitis B.

PMID- 15494914
TI  - Association between syphilis, antibodies to herpes simplex virus type 2, and
      recreational drug use and hepatitis B virus infection in the Women's Interagency
      HIV Study.
AB  - BACKGROUND: Liver disease is a leading cause of death in human immunodeficiency
      virus (HIV)-infected women; however, risk factors for hepatitis b virus (hbv)
      infection in this population have not been well studied. METHODS: We describe the
      seroprevalence and predictors of HBV infection in a cross-sectional analysis of
      2132 women with and at risk for HIV infection enrolled in the Women's Interagency
      HIV Study during the periods 1994-95 and 2001-02. Any test result positive for
      antibody to hepatitis B core antigen defined infection; those women with
      serological evidence of vaccine immunity were excluded from analysis. Women were
      stratified into those with a history of injection drug use (IDU), those with a
      history of noninjection drug use (non-IDU), and those with no history of illicit
      drug use. RESULTS: Of 1606 HIV-infected and 526 HIV-uninfected women, 7% and 12%,
      respectively, appeared to be vaccine immune. After exclusion of these women, 43%
      of 1500 HIV-infected and 22% of 461 HIV-uninfected women had HBV infection. HBV
      infection prevalence differed among the IDU, non-IDU, and no illicit drug use
      groups (76%, 30%, and 17%, respectively; P<.0001). HBV infection was strongly
      associated with herpes simplex virus 2 (HSV-2) seropositivity in the IDU group
      (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.6-5.4) and with a history
      of syphilis in the non-IDU group (OR, 2.7; 95% CI, 1.4-5.0). DISCUSSION: We found
      a high prevalence of HBV infection in our cohort of women with and at risk for
      HIV infection. HSV-2 seropositivity and a history of syphilis appeared to be
      important correlates of HBV infection. Sexual transmission of HBV, particularly
      in those with a history of genital ulcer disease, should be a major focus of
      education in all high-risk groups.

PMID- 15494915
TI  - Mitochondrial DNA levels in fat and blood cells from patients with lipodystrophy
      or peripheral neuropathy and the effect of 90 days of high-dose coenzyme Q
      treatment: a randomized, double-blind, placebo-controlled pilot study.
AB  - BACKGROUND: Mitochondrial toxicity can be induced by reverse-transcriptase
      inhibitors, and an association between levels of mitochondrial DNA (mtDNA) per
      cell and lipodystrophy, peripheral neuropathy, and HIV infection per se has been
      suggested. Studies aimed at increasing the oxidative capacity in HIV-infected
      patients have been sparse. METHODS: Levels of mtDNA in fat and peripheral blood
      mononuclear cells (PBMCs) from 25 HIV infected patients and 10 healthy control
      subjects were studied with real-time PCR analysis. A placebo-controlled and
      double-blind design was used to assign individuals to receive either 100 mg of
      coenzyme Q twice daily for 3 months or a matching placebo regimen. Levels of
      mtDNA and other parameters were assessed before and after the intervention
      period. RESULTS: The mean number of mtDNA copies per cell was lower in fat tissue
      obtained from patients with peripheral neuropathy (1547 mtDNA copies/cell;
      P=.045), patients with lipodystrophy (1732 mtDNA copies/cell; P=.003) and in HIV
      patients with no complications associated with highly active antiretroviral
      therapy (2935 mtDNA copies/cell; P=.078), compared with healthy control subjects
      (6198 mtDNA copies/cell). No clear difference was seen in mtDNA content in PBMCs.
      Coenzyme Q therapy improved the general condition of patients (P=.005) and caused
      a reversible increase in peripheral neuropathy pain (P=.048). Compared with
      placebo, treatment with coenzyme Q did not result in changes in mtDNA levels in
      fat cells or in PBMCs after the treatment period. CONCLUSIONS: Levels of mtDNA in
      fat tissue, but not in PBMCs, were associated with peripheral neuropathy and
      lipodystrophy. High-dose coenzyme Q therapy increased well-being in asymptomatic
      HIV-infected patients and those with lipodystrophy, as well as in control
      subjects, but aggravated pain in patients with peripheral neuropathy.

PMID- 15494916
TI  - Trends in AIDS-defining and non-AIDS-defining malignancies among HIV-infected
      patients: 1989-2002.
AB  - In a comparison of rates of acquired immunodeficiency syndrome (AIDS)-defining
      malignancies (ADMs) for 1989-1996 versus 1997-2002, we found a decrease in ADMs
      (rate ratio, 0.31; P<.0001) and a significant increase in non-AIDS-defining
      malignancies (non-ADMs; rate ratio, 10.87; P<.0002). The mean CD4 cell count was
      lower among patients with ADMs than among those with non-ADMs. A longer duration
      of survival during highly active antiretroviral therapy might explain the
      increasing incidence of non-ADMs.

PMID- 15494917
TI  - Positive predictive value of Gen-Probe APTIMA Combo 2 testing for Neisseria
      gonorrhoeae in a population of women with low prevalence of N. gonorrhoeae
      infection.
AB  - We collected specimens from women who tested positive for Neisseria gonorrhoeae
      using the Gen-Probe APTIMA Combo 2 (AC2), and we performed confirmatory tests
      using a nucleic acid amplification test (NAAT) that targets alternate gonococcal
      nucleic acid sequences. Among 59,664 specimens, 280 (0.47%) had positive results
      using AC2; 265 of these specimens were tested using the confirmatory NAAT, of
      which 258 yielded positive results (positive predictive value, 97.4%; 95%
      confidence interval, 95.1%-98.8%). Routine confirmatory testing of specimens with
      positive AC2 gonorrhea test results is not indicated.

PMID- 15494918
TI  - Molecular detection of Bartonella henselae DNA in the dental pulp of 800-year-old
      French cats.
AB  - Bartonella species are responsible for chronic bacteremia in domestic cats, which
      raises a question about the antiquity of the relationship between Bartonella
      species and cats that act as reservoirs for the organism. The sequencing of
      Bartonella pap31 and groEL genes from the dental pulp of cats dating from the
      13th to 16th centuries identified the presence of B. henselae genotype Houston;
      the observation of a unique mutation in the results of PCR assays for Bartonella
      species ruled out modern DNA contamination of the dental pulp samples. We
      conclude that cats had bacteremia due to B. henselae 800 years ago.

PMID- 15494919
TI  - Scrub typhus: prevalence and diagnostic issues in rural Southern India.

PMID- 15494920
TI  - Positive predictive value of Epstein-Barr virus DNA detection in HIV-related
      primary central nervous system lymphoma.

PMID- 15494922
TI  - Confirmation of results of tests for West Nile virus infection in organ
      transplant recipients.

PMID- 15494923
TI  - Domestically acquired fluoroquinolone-resistant Campylobacter infection.

PMID- 15494925
TI  - Lack of evidence that false-positive Aspergillus galactomannan antigen test
      results are due to treatment with piperacillin-tazobactam.

PMID- 15494928
TI  - Platelia Aspergillus assay and potential cross-reaction.

PMID- 15494930
TI  - An in-vivo model to interrogate the transition from acute to chronic
      inflammation.
AB  - This study describes the modulation of the rodent foreign body giant cell (FBGC)
      response to subcutaneously implanted, biodegradable poly(lactide-co
      glycolide)/calcium phosphate (PLGA/CaP) composites by application of a thin
      surface coat of calcium phosphate. Macroporous PLGA/CaP composite scaffolds, with
      interconnecting macroporosity, were half coated with a 3mm thick layer of CaP by
      immersion in simulated body fluid. Half-coated scaffolds were implanted
      subcutaneously in the dorsum of male Wistar rats for 1, 4 and 8 weeks. Specimens
      were embedded in paraffin and tissue sections evaluated by light microscopy with
      particular reference to the FBGC response. Histomorphometry revealed that FBGCs
      were in contact with 6% (+/- 3.5%) of the uncoated half, at 1 week, but no FBGCs
      were seen on the coated half. By 4 weeks, FBGCs were seen on both the uncoated
      and coated halves of the scaffolds with 87% (+/-10%) and 36% (+/-4%) FBGC/polymer
      contact respectively. By 8 weeks these FBGC contact percentages had risen to 97%
      (+/-0.45%) in the case of the uncoated halves of scaffolds, but decreased to 22%
      (+/-4%) in the case of the CaP-coated halves. Thus the CaP coating abrogated the
      FBGC response to the underlying polymer. Such a model may prove useful in
      providing an experimental system whereby both the mechanisms of biocompatibility
      and the transition from acute to chronic inflammation could be interrogated.

PMID- 15494929
TI  - A review of bioceramics and fibrin sealant.
AB  - This review focuses on bone substitute composites made by mixing ceramic
      biomaterials with fibrin sealants. Different biomaterials such as coral, bone
      derived materials, bioactive glass ceramics, and synthetic calcium phosphate have
      been mixed with fibrin sealant, resulting in a combination of the biological
      properties of the two components. This type of association has not produced
      identical results in all studies. In the past for some, the addition of fibrin
      sealant to the biomaterial failed to produce any significant, positive effect on
      osteointegration, whereas others found a positive impact on bone colonization.
      Despite the negative biological effects reported previously, bioceramic-fibrin
      composites have been widely used in various types of bone surgery because they
      are easy to manipulate. In particular, the intra-operative preparation of these
      composites makes it possible to add bone growth factors or autologous
      osteoprogenitor cells prior to bone reconstruction. The bone growth factors and
      autologous osteoprogenitor cells associated with the bioceramic-fibrin composites
      should provide surgeons with tissue engineered grafts with enhanced
      osteointegrative properties. This review discusses both the advantages and
      disadvantages, as well as the future perspectives, of using bioceramic-fibrin
      composites in various clinical indications.

PMID- 15494931
TI  - Histopathologic classification of lung cancer: Relevance of cytokeratin and TTF-1
      immunophenotyping.
AB  - Histopathologic classification of lung carcinoma is important, as a prognostic
      factor and in the evaluation of treatment modalities. Although the World Health
      Organization classification of lung cancer is based on routine microscopy,
      immunohistochemistry is an important additional aspect in modern pathologic
      practice. This study examines whether the main histologic types of lung
      carcinomas are more reliably diagnosed with immunohistochemical technique using
      antibodies for the lung tissue-specific antigen thyroid transcription factor-1
      (TTF-1) and a panel of cytokeratin (CK) antibodies. Forty-five cases of lung
      cancer (12 squamous cell carcinoma, 13 small cell carcinoma, 11 adenocarcinoma, 9
      large cell carcinoma [LCC]/pleomorphic carcinoma) were stained with antibodies to
      CK CAM5.2, CK5, CK7, CK20, and TTF-1. All 45 cases were positive with CAM5.2, 16
      of 45 cases with CK5, 34 of 45 cases with CK7, 4 of 45 cases with CK20, and 29 of
      45 with TTF-1. Squamous cell carcinoma (epidermoid carcinoma) had the
      immunophenotype CK5+/TTF-1-, and at least 20% were also positive with CK7. Most
      nonepidermoid tumors had the "lung-specific" phenotype CK5-/TTF-1+; all small
      cell carcinomas had the phenotype CK5-/CK8+/TTF-1+, all adenocarcinomas CK5
      /CK7+/TTF-1+ and (more than 50%) of LCC CK5-/CK7+/TTF-1+. Thus, more than 50% of
      LCCs were of the same phenotype as adenocarcinomas. The immunophenotypes of the
      main histologic types of lung carcinoma are stable and highly reproducible.
      However, because of considerable overlapping, immunophenotyping should not be
      used alone for histopathologic classification of lung cancer, but only as an
      adjunct to light microscopy. It is also suggested that CK5+ lung carcinomas with
      basaloid features should be regarded as variants of squamous cell carcinoma and
      not as LCC.

PMID- 15494932
TI  - Solitary fibrous tumor of the spinal cord: a clinicopathologic study of two
      cases.
AB  - Two cases of solitary fibrous tumor of the spinal cord are described. The
      patients were two men, 36 and 47 years old. Clinically, they sought medical care
      because of progressive paresthesias or urinary incontinence caused by a nodular,
      fairly circumscribed intraspinal tumor of the cervical and thoracic spinal cord,
      respectively. Preoperative magnetic resonance images suggested meningioma. In
      both cases, laminectomy with tumor resection was carried out. Microscopically,
      the tumors featured short spindle cells haphazardly enmeshed in a collagenized
      ground substance. No atypia, necrosis, or significant mitotic activity was
      recognized. Tumor cells were positive for CD34, bcl2, vimentin, and, in one case,
      CD99. Both patients recovered from symptoms and are alive and well 12 and 18
      months, respectively, after surgical resection. The differential diagnosis
      includes meningioma, schwannoma, and hemangiopericytoma, all of which may occur
      in the spinal canal. A careful morphologic approach and the judicious use of
      immunohistochemistry may assist in distinguishing among these conditions,
      although some irreducible difficulties may be posed by hemangiopericytoma.
      Although solitary fibrous tumor of the spinal cord presents with fairly
      comparable clinical, instrumental, and pathologic patterns, we believe that
      compilation of more cases is needed to segregate it as a distinct
      clinicopathologic entity.

PMID- 15494933
TI  - Intraductal papilloma with "comedo-like" necrosis, a diagnostic pitfall.
AB  - Necrosis in the breast is more frequently associated with malignancies than
      benign conditions. In the latter, it may be diffuse as seen in infarcts,
      postpartum changes, and after anticoagulant therapy, or focal as in florid
      adenosis and juvenile papillomatosis. The goal of this study was to find other
      benign entities associated with necrosis. Using our pathology database from
      January 1994 to March 2003, we identified 10 cases of florid duct hyperplasia
      associated with luminal necrosis. Clinical information was collected and all
      slides were reviewed. The age of the patients ranged from 36 to 94 years (mean,
      53.2 years). All patients underwent an initial excisional biopsy except for one
      who had a core biopsy. Patients presented with a palpable mass (6 cases) a
      radiographic density (3 cases), or nipple discharge (1 case). Findings correlated
      with the presence of an intraductal papilloma with adjacent or associated florid
      duct hyperplasia. Within the central luminal spaces of the florid duct
      hyperplasia, cellular debris associated with necrosis was present and was
      morphologically identical to that seen in comedo intraductal carcinoma. In fact,
      in two of the four consultation cases, these lesions were initially diagnosed as
      comedo carcinoma. Re-excision performed in three cases showed no atypia or
      malignancy. It is important to recognize the presence of comedo-like necrosis in
      florid duct hyperplasia associated with or adjacent to intraductal papillomas of
      the breast and not to misinterpret these findings as intraductal carcinoma. The
      necrosis may be secondary to reactive changes within the intraductal papilloma.

PMID- 15494934
TI  - Desmoplastic infantile ganglioglioma: a rare tumor with an unusual presentation.
AB  - Desmoplastic infantile ganglioglioma (World Health Organization grade I) is a
      rare neoplasm. Despite their common large size and spectacular radiologic and
      histologic features, the prognosis after surgical resection is good. We present a
      new case of this tumor in a 14-month-old boy with a recent history of
      intracranial hypertension. Magnetic resonance imaging revealed a large tumor
      involving the left collateral trigone with dilatation of the lateral ventricles.
      Surgery revealed two separate solid tumors: one in the left falco-tentorial
      region and the other in the left rolandic area. Microscopic examination showed a
      proliferation of neoplastic astrocytes in reticulin-rich desmoplastic stroma
      associated with scattered ganglion cells. One year after surgery follow-up
      magnetic resonance imaging did not show tumor progression.

PMID- 15494935
TI  - Solitary central myofibroma presenting in the gnathic region.
AB  - Solitary myofibroma of adults is an uncommon neoplasm that typically arises in
      soft tissue and subcutaneous sites in the head and neck, but rarely within bone.
      When encountered in the jaws, the lesions exhibit clinical and radiographic
      features suggestive of an odontogenic tumor or cyst as well as several other
      neoplastic conditions. Tooth mobility, displacement of teeth, and dramatic jaw
      expansion may be observed. Analogous to other sites of involvement, gnathic
      myofibromas are biologically indolent and show little or no recurrence following
      excision. In rare instances, however, the ability to obtain adequate surgical
      margins by conservative measures may be limited; thus, issues of local control
      may supercede the importance of biologic potential. We present the radiologic and
      histopathologic findings in a case of central myofibroma presenting as a large
      lytic lesion of the mandible. Myofibroma involving the jaw bones represents a
      unique diagnostic and therapeutic challenge, and accurate diagnosis and
      management is predicated on careful correlation of radiographic and pathologic
      findings.

PMID- 15494936
TI  - Pituicytoma.
AB  - Pituicytoma is a rare, low-grade neoplasm that originates in the neurohypophysis
      of the pituitary gland. We report the clinicopathologic features of a pituicytoma
      arising in a 52-year-old man who presented with a mass and panhypopituitarism,
      clinically suggestive of a pituitary adenoma. The tumor was marked by a
      proliferation of elongated cells arranged in bundles and interlacing fascicles.
      The tumor demonstrated positive staining with S-100 protein and glial fibrillary
      acid protein antibodies. The tumor did not stain with antibodies to cytokeratin,
      synaptophysin, chromogranin, anterior pituitary hormones, or p53. An MIB-1
      labeling index of 1.1% was observed. The tumor was subtotally resected and
      recurred 11 months after the initial surgery. The literature on this rare tumor
      will be reviewed and differential diagnosis discussed.

PMID- 15494937
TI  - Low-grade endometrial stromal sarcoma presenting as vaginal nodule.
AB  - Endometrial stromal sarcoma is a rare neoplasm of the uterus. Extrauterine
      locations of this neoplasm, excluding metastases or local extension, are even
      more unusual and are usually associated with the presence of endometriosis. The
      authors report a case of endometrial stromal sarcoma presenting as a vaginal wall
      nodule, without any sign of primary uterine tumor after extensive evaluation or
      presence of endometriosis. The morphology, immunohistochemical profile,
      differential diagnoses, and pathogenesis are discussed, as well as a review of
      the literature on this issue.

PMID- 15494938
TI  - Pseudoneoplastic proliferation of histiocytes with paclitaxel-induced
      ultrastructural changes in a mastectomy specimen.
AB  - A 49-year-old Hispanic woman with a T4N1M0 infiltrating duct carcinoma of the
      left breast underwent four courses of FAC (doxorubicin 86 mg, 5-fluorouracil 860
      mg, cyclophosphamide 86 mg, and dexamethasone 10 mg) adjuvant chemotherapy plus
      four courses of paclitaxel (Taxol; Bristol-Myers Squibb Oncology, Princeton, NJ)
      and subsequent mastectomy. The tumor shrunk from 6.5 cm to 2.5 cm after the
      treatment. The residual tumor in the surgical specimen measured 1.5 cm with eight
      positive out of 24 axillary lymph nodes. The tumor showed typical chemotherapy
      changes and a massive proliferation of histiocytes that mimicked a neoplasm. A
      nodular proliferation of the same cells in one axillary node raised the
      impression of a second malignant tumor in the breast spreading to the node. The
      histiocytic cells contained lamellar and coarse periodic acid-Schiff-positive
      material distending their cytoplasm and they were strongly positive for CD68 and
      negative for CD1a, pan keratin, and S-100. These findings ruled out histiocytoid
      carcinoma, granular cell tumor, and Erdheim-Chester disease. The proliferating
      histiocytes had ultrastructural findings of paclitaxel-induced cytotoxicity with
      disorganized stacks of intermediate filaments positive for vimentin by
      immunostains and fewer masses of tubulin. The treated breast carcinoma cells were
      tubulin-positive but the proliferating histiocytes were tubulin-negative.

PMID- 15494939
TI  - Renal cell carcinoma metastatic to Hurthle cell adenoma of thyroid.
AB  - Metastases to the thyroid gland are a common finding at autopsy in patients who
      died of malignancy and are often misdiagnosed as primary thyroid neoplasms
      clinically. We present a patient with a rare, unusual case of renal cell
      carcinoma (RCC) metastatic to a Hurthle cell adenoma of the thyroid. A 53-year
      old woman was admitted to a University of Texas Medical Branch Hospital
      (Galveston, TX) for a large right thyroid mass that was present for 3 months. A
      fine needle aspiration of the thyroid mass was performed and interpreted as
      suggestive of a Hurthle cell neoplasm. A total thyroidectomy revealed Hurthle
      cell adenoma containing clusters of cytologically atypical cells with clear
      cytoplasm. Subsequent patient evaluation and computed tomography revealed a renal
      mass. Left radical nephrectomy was performed at a later date for left renal mass
      and the microscopic examination confirmed the diagnosis of primary clear cell
      carcinoma of the kidney. Further studies confirmed that the thyroid mass was
      metastases from RCC. Although carcinoma of the kidney is responsible in most
      instances of metastatic disease to the thyroid, metastatic RCC to a thyroid
      neoplasm is extremely rare, with only two reports found in the English
      literature. The possibility of metastatic RCC should always be taken under
      consideration, especially when nests of clear cells are seen infiltrating into
      the thyroid parenchyma or neoplasm.

PMID- 15494940
TI  - Lymphoepithelioma-like carcinoma of the breast: report of a case mimicking
      lymphoma.
AB  - Only 10 cases of lymphoepithelioma-like carcinoma of the breast have been
      reported in the literature. This report adds one more case to the published
      literature. A 62-year-old woman presented with a mass in her left breast on
      physical examination. The mammographic images showed a 3.0 cm, poorly defined
      mass in the upper outer quadrant. A biopsy was recommended. The gross specimen
      consisted of a 5 cm portion of breast parenchyma with no discrete tumor. On
      microscopic examination, the tumor was composed of sheets of epithelioid cells
      arranged as single cells or in cords partially obscured by a dense lymphocytic
      infiltrate. The epitheliod cells extensively expressed cytokeratin stain, but did
      not express E-cadherin. The lymphoid cells expressed L26 stain in the germinal
      centers, and CD3 stain in the T lymphocytes surrounding the germinal centers and
      in between tumor cells. In situ hybridization showed no evidence of Epstein-Barr
      virus infection in the tumor cells. An overall review of 11 cases shows that the
      disease is usually seen in older patients. In situ and invasive lobular component
      was reported in 36% of the cases. Eight of 11 were negative for E-cadherin, 36%
      were estrogen receptor-positive, 18% were progesterone receptor-positive, and all
      of them were HER2/neu negative. None of the reported cases have been associated
      with Epstein-Barr virus infection. Only two of the cases showed lymph node
      metastasis, and long-term follow-up in one of them showed good prognosis. In
      summary, lymphoepithelioma-like carcinoma of the breast is a tumor with a good
      prognosis that should be considered as a possible diagnosis in breast tumors with
      an intense lymphocytic infiltrate.

PMID- 15494941
TI  - Allergic fungal sinusitis is a histopathologic diagnosis; paranasal mucocele is
      not.
AB  - Allergic fungal sinusitis has been known to pathologists for two decades. During
      this time, multiple articles have stressed that the condition continues to be
      underdiagnosed. This is true, but it can also be overdiagnosed. This means that
      series of cases used for clinical studies usually are "contaminated" with cases
      that are misdiagnosed. Because the condition is often quite problematic to
      control, determination of the best treatment regimens is important. This will be
      dependent on clinical studies including only correctly diagnosed cases for study.
      This article discusses the steps toward making the correct diagnosis.

PMID- 15494944
TI  - Recurrent fever in a healthy-appearing child.

PMID- 15494946
TI  - Management of children with infection-associated persistent diarrhea.
AB  - Diarrhea is the leading cause of death in children younger than 5 years of age;
      persistent diarrhea accounts for 30 to 50 percent of those deaths in developing
      countries. Malnutrition, immunosuppression, young age, and an increase in the
      preceding diarrhea burdens are risk factors for the development of persistent
      diarrhea. Although many viruses, bacteria, and parasites can produce persistent
      diarrhea, enteropathogenic Escherichia coli , enteroaggregative E. coli, Giardia,
      Cryptosporidium , and Cyclospora are the most important of these agents. With
      currently available tests, identifying a specific cause usually is difficult.
      Newer sensitive molecular tests must be used for studying the epidemiology of
      persistent diarrhea in children. Management includes rehydration, adequate diet,
      micronutrient supplementation, and antimicrobials. Persistent diarrhea seriously
      affects nutritional status, growth, and intellectual function. Meeting these
      challenges is profoundly important, particularly in developing countries.

PMID- 15494945
TI  - Human milk protection against infectious diarrhea: implications for prevention
      and clinical care.
AB  - Breastfeeding is the major strategy for prevention of morbidity and mortality
      resulting from diarrhea in the first few years of life. Health-system and
      community based interventions have been shown to increase the prevalence of
      breastfeeding and reduce the incidence of diarrhea and associated healthcare
      costs in infancy. The protective effect of breastfeeding is attributable to a
      complex of acquired and innate factors unique to human milk that have anti
      infective, anti-inflammatory, and immunoregulatory functions, including secretory
      antibodies, oligosaccharides, glycoconjugates, lactoferrin, leukocytes,
      cytokines, and other agents. The American Academy of Pediatrics recommends
      exclusive breastfeeding until the infant is approximately 6 months of age, with
      timely introduction of complementary foods and continued breastfeeding to a year,
      or longer if desired. The number of deaths of children that could be prevented
      worldwide each year if these breastfeeding recommendations were followed has been
      estimated to be more than 1 million.

PMID- 15494947
TI  - Human caliciviruses and pediatric gastroenteritis.
AB  - Surveillance using molecular diagnostic methods developed in the past decade
      shows that human caliciviruses, particularly the Noroviruses, are the most
      important cause of pediatric acute gastroenteritis, next to rotavirus.
      Noroviruses also cause severe gastroenteritis in children, requiring
      hospitalization. The Sapovirus, a morphologically and genetically distinct genus
      of calicivirus, cause mainly milder endemic pediatric gastroenteritis.
      Noroviruses and Sapoviruses are genetically and antigenetically diverse, and
      multiple genetic types cocirculate in the same community. Human caliciviruses
      still cannot be cultivated in cell culture or in an animal model. Significant
      progress has been made in the past decade in the classification, diagnosis, and
      vaccine development, as well as in the recent discovery of Norovirus recognizing
      human histoblood group antigens as receptors. Major developments in this field
      are expected to occur in the near future.

PMID- 15494948
TI  - Shigella infections in children: new insights.
AB  - Shigellosis , the acute enteric infection caused by bacteria of the genus
      Shigella , has a worldwide distribution with an estimated annual incidence of
      164.7 million cases, of which 163.2 million occur in developing countries, and
      1.1 million deaths. Sixty-nine percent of all episodes and 61 percent of all
      Shigella -related deaths involve children younger than 5 years old. In the United
      States, 10,000 to 15,000 cases of shigellosis are reported each year. Although
      usually confined to the colonic mucosa, shigellosis sometimes can cause
      extraintestinal complications. Recent publications have shed light on the
      clinical characteristics of Shigella -induced bacteremia, surgical complications,
      urogenital symptoms, and neurologic manifestations, and on the unique
      manifestations in the neonatal period. The mainstay of treatment of shigellosis
      in children is correction of the fluid and electrolyte loss, which often is
      achieved by the administration of oral rehydration solutions. Appropriate
      antibiotic therapy shortens the duration of both clinical symptoms and fecal
      excretion of the pathogen. However, the increasing antimicrobial resistance of
      shigellae worldwide constitutes a major problem. Regarding the pathophysiology of
      shigellosis and its complications, recent data not only elucidated the molecular
      mechanisms involved but also linked manifestations of disease to the interplay of
      bacterial virulence factors and host responses. The improved understanding of the
      pathophysiology is hoped to lead to innovative therapeutic approaches against
      shigellosis and new generations of vaccine candidates.

PMID- 15494949
TI  - Cryptosporidiosis in children.
AB  - Cryptosporidiosis is an important enteric parasitic infection that is associated
      with significant morbidity and mortality, especially among individuals who are
      immunosuppressed and infants and children in the developing world. The
      seroprevalence of this pathogen is high worldwide, suggesting that exposure
      occurs commonly. The routes of Cryptosporidium spp. transmission are waterborne,
      food-borne, and occasionally person-to-person. Infected patients can be
      asymptomatic or develop watery diarrhea and associated enteric symptoms, which
      are self-limited in immunocompetent persons. In contrast, immunodeficient
      individuals develop severe, chronic diarrhea that rarely can lead to extra
      intestinal cryptosporidiosis. Although the diagnosis of Cryptosporidium infection
      can be established by examining a modified acid-fast stain of stool for the
      presence of oocysts, enzyme-linked immunoassays are now the diagnostic modalities
      of choice. Recent clinical trials in pediatric cryptosporidiosis have shown
      nitazoxanide to be effective therapy.

PMID- 15494950
TI  - The role of Shiga-toxin-producing Escherichia coli in hemorrhagic colitis and
      hemolytic uremic syndrome.
AB  - The Shiga-toxin-producing E. coli represent a major class of pathogens that have
      been defined over the last twenty years. They cause distinctive clinical
      manifestations such as afebrile bloody diarrhea with severe abdominal pain
      (hemorrhagic colitis) and microangiopathic hemolytic anemia with renal failure
      (hemolytic uremic syndrome). The most common Shiga-toxin-producing E. coli is
      serotype O157:H7, although at least one hundred different serotypes share the
      virulence traits and clinical manifestations with this organism. Understanding
      the pathophysicology, improving diagnostic tools, and developing a treatment
      strategy are important areas of ongoing investigations.

PMID- 15494951
TI  - Enteroaggregative Escherichia coli: an emerging pathogen in children.
AB  - Enteroaggregative Escherichia coli (EAEC) is an emerging pathogen that causes
      enteric and food-borne infectious diseases. Children throughout the world appear
      to be susceptible to EAEC infection. EAEC pathogenesis involves the following
      three stages: 1) adherence to the intestinal mucosa; 2) increased production and
      deposition of a mucus biofilm; and 3) mucosal toxicity due to inflammation and
      cytokine release. The HEp-2 cell adherent assay allows identification of EAECs
      characteristic aggregative or "stacked brick" adherence pattern. Antimicrobial
      treatment of children who develop an EAEC infection should be individually based.
      All children with EAEC diarrhea should receive adequate oral fluid hydration. For
      children who have persistent diarrhea and severe dehydrating illness despite
      having received adequate oral rehydration, antimicrobials may be initiated.
      Azithromycin and rifaximin have been shown to shorten the course of EAEC diarrhea
      in adults and probably represent the recommended antimicrobials of choice for
      children with severe or persistent illness. The objective of this review is to
      increase awareness of this important emerging pathogen and to discuss the
      epidemiology, pathogenesis, and pathogen and host factors associated with EAEC
      infection in children.

PMID- 15494952
TI  - Vaccines against diarrheal diseases.
AB  - At least 2 million persons succumb annually to enteric infection, and in
      countless other patients, diarrheal disease aggravates malnutrition and
      susceptibility to other infections. Prevention of enteric illness by virtue of
      improved hygiene and provision of sanitation and water treatment is impractical
      in most developing countries, where morbidity and mortality rates are highest.
      For this reason, development of vaccines against the most important
      gastrointestinal infections remains a high priority.

PMID- 15494953
TI  - Monkeypox: a review of the history and emergence in the Western hemisphere.
AB  - A mysterious disease was reported on May 24, 2003, when the Wisconsin Division of
      Public Health (DPH) received notice of a 3-year-old girl who had been
      hospitalized in central Wisconsin with cellulites and fever after being bitten by
      a prairie dog on May 13. The laboratory isolated a gram-negative bacillus,
      raising concerns that it might be tularemia or plague; ultimately, it was
      identified as an acinetobacter species and was considered to be a contaminant.
      Because no other such cases were reported at the time, the case was thought to be
      merely an isolated event. However, within two weeks, on June 2, 2003, evidence of
      a much wider scenario began to emerge. On that date, the Wisconsin DPH received
      notice from the Marshfield Laboratory that the mother of the first patient had
      become ill on May 26 and that electron-microscopic evidence of a poxvirus was
      found in a skin lesion. On that same day, another report, this time from the
      Milwaukee Health Department, of a strange illness was received at the DPH and
      described the case of a meat inspector who resided in southeastern Wisconsin and
      also was a distributor of exotic animals. By July 30, 2003, 72 confirmed or
      suspected cases of monkeypox had been reported in Wisconsin, Illinois, and
      Indiana and represented a large outbreak. The peak in the onset of illness
      occurred between May 29 and June 9, 2003, and no further cases of illness have
      been reported in humans since June 22, 2003. Traceback investigations from the
      child and other patients followed the route of introduction of monkeypox into
      Wisconsin to a distributor in Illinois, who had received a shipment of exotic
      animals imported into the United States through Texas from Ghana, West Africa.

PMID- 15494954
TI  - Isaac Arthur Abt (1867-1955). 1957.

PMID- 15494956
TI  - The reemergence of academic-service partnerships: responses to the nursing
      shortage, work environment issues, and beyond.

PMID- 15494957
TI  - The ethical foundation of yoga.

PMID- 15494958
TI  - A rose by any other name?

PMID- 15494959
TI  - Readiness and response to public health emergencies: help needed now from
      professional nursing associations.

PMID- 15494960
TI  - Hardwiring the "three-legged stool": nursing's vital education/practice/research
      triad.

PMID- 15494961
TI  - Beyond tradition: synergizing intellectual and material capital to forge the new
      academic-service partnership.
AB  - Academic-service partnerships are being touted as a solution to workforce
      problems. "Traditional" approaches to these partnerships have been directed
      primarily at academic and hospital institutions for mutual benefit. An expanded
      model of partnership possibilities is presented through three detailed exemplars
      that include population health (with descriptors from an Institute of Medicine
      study addressing the public's health in the 21st century), public-private
      ventures (public institution with faith-based and community agencies), and
      nursing-corporate opportunities (academia and a proprietary information
      technology corporate supplier). The benefits of these expanded partnerships and
      the criteria for selecting a partnership sensitive to the scholarship of practice
      and the mission/purpose/goals of each partnering organization is highlighted.

PMID- 15494962
TI  - Building transformational partnerships in nursing.
AB  - Over the past decade, the nursing education and delivery system has moved to
      respond to the crisis in nursing workforce and to prepare itself for what
      promises to be a long and, at times, challenging struggle. Although much progress
      has been made, it is increasingly apparent that there are limits to what might be
      gained from primarily unilateral efforts. Already, issues such as scope of
      vision, resource constraints, and sustainability are beginning to crop up from
      even the best of the institutionally based efforts. What is becoming apparent to
      many leaders in organizations attempting to address these issues is that they
      cannot go it alone. They must develop partnerships with others in the education
      care continuum to have any real hope of mounting and sustaining an effort to
      build the programs needed to address the long-term challenges of a nursing
      workforce that is adequate in number and skill. As this realization comes to
      consciousness, these leaders are becoming more aware of the need for partnerships
      as the foundation for a different type of strategic response. In taking the early
      steps toward a partnership, leaders are becoming sensitive to the different
      demands that a true partnership places on them and their colleagues. These
      demands may be periodically daunting, but they point to a set of outcomes that
      may actually have greater consequences for the public and patients. This article
      is about the creation, care, and feeding of these partnerships.

PMID- 15494963
TI  - A present-day academic perspective on the Carolina nursing experience: building
      on the past, shaping the future.
AB  - Past, present, and future models of academic-service collaboration are described
      and projected from an academic perspective. The features that characterize
      academic-service partnerships during the history of nursing education in America,
      the goals that drove faculty and academic leaders to engage or disengage in
      earlier partnerships, and new forms of emerging partnerships are presented, along
      with a discussion of their importance in the context of environmental change. The
      foundation for building the Carolina Model between the University of North
      Carolina-Chapel Hill and the University of North Carolina Hospitals is a
      prototype for extending future academic-service initiatives.

PMID- 15494964
TI  - The Carolina nursing experience: a service perspective on an academic-service
      partnership.
AB  - There is a renewed interest in and commitment to the strengthening of academic
      service partnerships. This article will explore the developing relationship
      between the University of North Carolina at Chapel Hill School of Nursing and the
      University of North Carolina Hospitals--an example of a research
      university/academic medical center arrangement. The roles of academic and service
      leaders will be presented in terms of both the formation and maintenance of the
      partnership. The benefits for the various stakeholders will be presented.

PMID- 15494965
TI  - Collaboration: aligning resources to create and sustain partnerships.
AB  - Academic-service partnerships are the future. These partnerships require a new
      paradigm and new practice models that necessitate change in how and where
      decisions are made as well as who is accountable for both the decisions and the
      outcomes of those decisions. The role of organizational leaders in this new
      paradigm becomes aligning resources to create and sustain partnerships.
      Partnerships are relationships and are only as effective as the communication
      between all entities. Decision-making is an important outcome of partnerships,
      yet there is little research regarding specific behavioral strategies that
      promote quality problem solving and decision-making. This paper extends the work
      of organizational theorist Ralph Stacey by proposing an event-driven typology of
      behavioral strategies for problem solving. The typology can assist organizational
      leaders to align resources for best practices in academic-service partnerships
      and be used as a framework for future research.

PMID- 15494966
TI  - Nursing faculty satisfaction with individual, institutional, and leadership
      factors.
AB  - A survey of full-time nursing faculty in Minnesota examined perceptions about
      individual, institutional, and leadership characteristics. Of 548 surveys sent,
      298 responses were analyzed (54 percent). Faculty were, on average, 50.5 years
      old, female (96 percent), and white (97 percent). Approximately 82 percent would
      choose nursing again, 63 percent would choose to work in their current
      institutions, and only 9 percent would not choose a faculty career again. Ninety
      eight percent were committed to their careers and 97 percent to the profession.
      Only 44 percent had confidence in nursing's direction. Similarities among faculty
      included having input into their roles and time; clarity about their work and
      goals fitting with the schools' vision and goals; the role of the dean and senior
      faculty in maintaining the vision; the sense that their opinions are routinely
      solicited and incorporated; and compensation is not fair for the work that is
      done. Most (80 percent) felt that there were effective communication systems,
      constructive feedback from colleagues (71 percent), and a supportive network in
      their departments (55 percent). Differences related mostly to role functions; for
      example, baccalaureate and graduate faculty were more involved and had greater
      skills, rewards, and resources in research, and faculty in associate's degree and
      licensed practical nurse programs perceived greater support for providing patient
      care. Recommendations are given for creating supportive work environments for
      faculty.

PMID- 15494967
TI  - This new house: building knowledge through online learning.
AB  - The purpose of this study was to understand from baccalaureate-degree nursing
      students the experience of virtual learning in nursing and to understand how
      online education enhanced and detracted from learning. Three in-depth, focus
      group interviews were conducted with a total of 27 baccalaureate nursing
      students. Hermeneutic phenomenology was employed to analyze the narrative data.
      Seven themes were identified from the data. The first theme was "making the
      framework": (1) providing flexibility; (2) enabling students through observing,
      guiding, and modeling; (3) faculty as facilitators; and (4) questioning as
      method. The second theme was "building incredible dialogue": (1) having great
      discussions, (2) sharing ideas/knowledge, and (3) not being inhibited. The third
      theme was "critical thinking--the 3-D effect": (1) sitting with the words, (2)
      using references/research, (3) seeing a variety of perspectives, (4) critiquing
      self and others, and (5) using selective language. The fourth theme was "personal
      and professional growth": (1) being connected, (2) feeling valued and respected,
      and (3) having intimate relationships. The fifth theme, representing the outcomes
      for online courses, was "more comprehensive learning": (1) deeper understanding
      and (2) better retention of knowledge. The sixth theme was "being overwhelmed",
      and the seventh theme was "being frustrated". As a result of this study, an
      understanding of the phenomenon of online learning was developed. The findings
      provide direction for future development of the pedagogy of distance learning.

PMID- 15494968
TI  - Is torus palatinus a feature of a well-developed maxilla?
AB  - Torus palatinus (TP) is an exostosis of the hard palate. The biologic
      significance of TP is unknown. Our hypothesis was that the presence of a TP
      reflects the development of the maxilla. It has been proven that tooth agenesis
      is associated with small maxillary size. We investigated whether there is a
      relationship between maxillary third molar agenesis and the presence or absence
      of TP. The study was carried out on 253 Turkish patients. It showed a lower
      prevalence of third molar agenesis in female subjects with TP (P < 0.001). This
      study provides indirect evidence that development of the maxilla may be greater
      in female subjects with TP.

PMID- 15494969
TI  - Linear parameters of normal and abnormal cava septi pellucidi: a post-mortem
      study.
AB  - Anatomical variations in the dimensions of different brain structures have been
      correlated with clinical syndromes. This study on the parameters of normal and
      abnormal cavum septi pellucidi (CSP) can be of clinical significance. We obtained
      479 brains from autopsied persons (310 males and 169 females, 377 normal or
      asymptomatic and 102 abnormal or symptomatic persons, aged 22-89 years) and
      observed that 110 brains (75 males and 35 females) had CSP. These cava were
      classified into two groups depending on the past medical histories of the
      autopsied person: 40 asymptomatic and 70 symptomatic cava. We have defined
      symptomatic cava as those in autopsied persons who had known past medical history
      of psychiatric or neurological disease. Asymptomatic cava were in autopsied
      persons who had no known past medical history of psychiatric or neurological
      disease. The CSP parameters (length, width, depth) of the symptomatic and
      asymptomatic groups were measured and were statistically analyzed. Analysis
      showed that the cava in the symptomatic group were significantly longer and
      wider. Discriminant function analysis was used to derive a mathematical formula
      to classify CSP into an asymptomatic or symptomatic group based on length and
      width measurements of the cavum.

PMID- 15494970
TI  - Movements at the low back during normal walking.
AB  - We present a technique for measuring the kinematics of the functional low back
      during normal gait. We have used a similar technique previously to measure low
      back movement simultaneously with hip, knee, and ankle movement during the toe
      touching manoeuvre. We noted that movements at the low back were biphasic. The
      greatest low back movements were found to occur in the transverse plane (mean =
      23 degrees), whereas a mean of 17 degrees movement occurred in the coronal plane
      and only 5 degrees movement in the sagittal plane. These findings confirm, using
      a non-invasive technique, that there are significant ranges of movement at the
      low back during walking and lend some support to the theory that rotational
      movement at the low back is a major component of human locomotion.

PMID- 15494971
TI  - Reply to "Anatomy of renal arterial supply".

PMID- 15494972
TI  - Postsurgical disparity in survival between African Americans and Caucasians with
      colonic adenocarcinoma.

PMID- 15494974
TI  - Treatment outcomes of three-dimensional conformal radiotherapy for localized
      prostate carcinoma: a large community-based experience.
AB  - BACKGROUND: The current study documented the implementation of three-dimensional
      conformal radiotherapy and assessed the tumor control and toxicity of such
      treatment in a large, multisite community practice. METHODS: The authors
      retrospectively reviewed their first 222 consecutive patients with clinically
      localized (N0) prostate carcinoma treated with a 6-field conformal technique from
      October 1993 through March 2000. Standardized target definitions, dose planning
      constraints, and gantry angles were utilized to develop the treatment plan.
      Patients were categorized by low, intermediate, and high risk. Low risk was
      defined as T1a-T2a disease, a Gleason score < 7, and prostate-specific antigen
      (PSA) level </= 10.0 ng/mL (n = 47 [21%]). Intermediate risk was defined as T2b
      disease, a Gleason score > 6, or PSA level > 10.01 ng/mL (n = 60 [27%]). High
      risk was defined as 2 of the above risk factors or as T3 disease, a Gleason score
      > 7, or a PSA level > 20 (n = 115 [52%]). Biochemical disease recurrence was
      defined in accordance with the American Society for Therapeutic Radiology and
      Oncology definition. Urinary and bowel toxicity were graded using the Radiation
      Therapy Oncology Group morbidity scoring system. RESULTS: The median follow-up
      after radiotherapy for surviving patients was 47 months (range, 0-99 months). The
      2 and 5-year actuarial biochemical control rates for all patients were 84% and
      78%, respectively. Using logistic regression analysis, lower dose (< 75.6 gray
      [Gy] vs. 75.6 Gy; P = 0.006), higher risk group (P = 0.033), higher stage (P =
      0.045), and higher PSA level (P = 0.001) were significantly associated with
      biochemical disease recurrence. Toxicity was not significantly correlated with a
      higher radiotherapy dose. CONCLUSIONS: Dose escalation to 75.6 Gy using a 6-field
      conformal technique was feasible in the authors' community practice and resulted
      in acceptable toxicity and early biochemical outcomes.

PMID- 15494975
TI  - Defining the best available treatment for neurocytomas in children.
AB  - BACKGROUND: In children, neurocytomas are extremely rare tumors in the central
      nervous system. Since this entity was introduced in 1982, approximately 60 cases
      have been reported among patients age </= =18 years of age. The current analysis
      was performed to define the best available neurocytoma therapy in children.
      METHODS: All reported neurocytoma cases were reviewed for age, extent of
      resection, radiotherapy, radiotherapy dose, local control, and survival. Data
      were obtained from the literature and the authors. Statistical analysis was
      performed with the Kaplan-Meier method and log-rank test. RESULTS: Fifty-nine
      children were categorized by therapy: complete tumor resection (CTR; n = 20),
      complete tumor resection plus radiotherapy (CTR-RT; n = 11), incomplete tumor
      resection (ITR; n = 14), and incomplete tumor resection plus radiotherapy (ITR
      RT; n = 14). Local control rates were better after CTR, CTR-RT, and ITR-RT than
      after ITR, at 5 years (86%, 100%, and 100% vs. 60%; P < 0.001) and at 10 years
      (86%, 100%, and 100% vs. 45%; P < 0.001). The 5-year and 10-year survival rates
      were 100% after CTR, 100% after CTR-RT, 100% after ITR-RT, and 93% after ITR (P =
      0.4). In the ITR-RT group, no difference was observed between doses </= 50 gray
      (Gy) and >/= 54 Gy when compared for local control (P = 1.0) and survival rates
      (P = 1.0). Radiotherapy-related psychomotor retardation or secondary brain tumors
      were not reported. CONCLUSIONS: The prognosis of children with neurocytomas is
      extremely good. CTR was associated with better local control and survival rates
      than ITR. After ITR, radiotherapy improves local control, but not survival. If
      postoperative radiotherapy is considered, a dose of 50 Gy was appropriate for
      long-term local control in children, whereas higher doses were required in
      adults.

PMID- 15494976
TI  - Multiple primary soft tissue sarcomas.
AB  - BACKGROUND: The synchronous or metachronous development of multiple primary soft
      tissue sarcomas (STS) of different histopathology has been reported only in
      isolated case reports. METHODS: The records of patients who developed multiple
      primary STS and who were treated at a tertiary cancer center between 1982 and
      2003 were reviewed. RESULTS: Nine patients with multiple primary STS were
      identified, representing 0.2% of all patients who were treated for STS. The
      median age of patients at the time of initial presentation with sarcoma was 60
      years (range, 51-81 years). Most patients in this series (n = 7) had metachronous
      development of a second primary STS. The incidence of second primary sarcomas in
      patients who were diagnosed previously with STS (4.0 per 10,000 population per
      year) was significantly greater than the incidence of primary STS in the general
      population (3.2 per 100,000 population per year; P < 0.01). CONCLUSIONS: Although
      it is an uncommon occurrence, patients who have a history of STS are at an
      increased risk for the development of a second primary STS.

PMID- 15494977
TI  - Implementation of DNA cytometric measurements in fine-needle aspiration biopsy
      diagnostics of breast disease.
AB  - BACKGROUND: For this study, the diagnostic protocol included fine-needle
      aspiration biopsy (FNAB) and DNA cytometric measurements. The objective of the
      study was to improve the diagnostic sensitivity of FNAB. METHODS: Sixty-eight
      FNAB samples were stained using the Feulgen stain, and DNA histograms were
      produced by selecting the nuclei of cell groups and free cells separately.
      RESULTS: Among 28 samples that were classified as definitely benign (n = 17
      samples) or atypical but benign (n = 11 samples), DNA cytometry generally showed
      diploid/peridiploid peaks. Three of those samples were associated later with
      carcinoma. In those samples DNA cytometry did not improve sensitivity. Among
      moderately atypical samples (n = 17 samples), 8 samples were diagnosed later as
      carcinoma. DNA cytometry helped the diagnostic procedure in 62.5% of those
      samples. Among 21 samples that were classified as highly suspicious (n = 10
      samples) or definitely malignant (n = 11 samples), DNA cytometry generally showed
      atypical DNA histograms (20 of 21 histograms), and DNA cytometry supported the
      diagnosis of carcinoma in 95.2%. Histograms that were based on free cells
      frequently were more abnormal compared with histograms that were based on cell
      groups. Histologically verified benign lesions also could show abnormalities in
      DNA histograms. Accepting wider gates than are used normally for primarily
      Feulgen stained samples on these restained samples resulted in improved
      specificity, efficiency, and predictive values. CONCLUSIONS: DNA cytometry has a
      potential to support the differential diagnosis of breast lesions, and sampling
      of free cells increases sensitivity. Benign breast lesions (fibrocystic disease,
      fibroadenoma) included DNA-cytometrically abnormal cell clones and showed
      tendencies toward polyploidy, which should be included in the diagnostic
      criteria.

PMID- 15494978
TI  - Tissue plasminogen activator and glial function.
AB  - Tissue plasminogen activator (tPA) is the only FDA-approved treatment of
      thrombotic stroke and is a major parenchymal serine protease in the brain.
      However, it has been implicated in a plethora of brain pathologies, raising
      concern about its use as a safe therapeutic. tPA is thought to regulate
      physiological processes that entail tissue remodeling and plasticity, purportedly
      due to its ability to initiate the degradation of extracellular matrix proteins
      and possibly other substrates. Understanding the physiological role(s) of tPA
      promises to both elucidate important aspects of brain function and improve the
      available therapies for neurological disease. In this context, the effects of tPA
      on glial cells, mainly microglial cells, but also astrocytes and Schwann cells,
      appear to be of particular importance, given the increasing awareness of the
      significance of glia in brain physiology and pathology

PMID- 15494979
TI  - Caveolin and GLT-1 gene expression is reciprocally regulated in primary
      astrocytes: association of GLT-1 with non-caveolar lipid rafts.
AB  - Caveolae represent membrane microdomains acting as integrators of cellular
      signaling and functional processes. Caveolins are involved in the biogenesis of
      caveolae and regulate the activity of caveolae-associated proteins. Although
      caveolin proteins are found in the CNS, the regulation of caveolins in neural
      cells is poorly described. In the present study, we investigated different modes
      and mechanisms of caveolin gene regulation in primary rat astrocytes. We
      demonstrated that activation of cAMP-dependent signaling pathways led to a marked
      reduction in protein levels of caveolin-1/-2 in cortical astrocytes. Application
      of transforming growth factor-alpha (TGF-alpha) also resulted in a decrease of
      caveolin-1/-2 expression. Decreased caveolin protein levels were mirrored by
      diminished caveolin gene transcription. The repressive effect of TGF-alpha on
      caveolin-1 expression was MAP kinase-independent and partly mediated through the
      PI3-kinase pathway. Further downstream, inhibition of histone deacetylases
      abrogated TGF-alpha effects, suggesting that chromatin remodeling processes could
      contribute to caveolin-1 repression. Intriguingly, alterations of caveolin gene
      expression in response to cAMP or TGF-alpha coincided with reciprocal and brain
      region specific changes in glial glutamate transporter GLT-1 expression. The
      reciprocal regulation of caveolin-1 and GLT-1 expression might be gated through a
      common PI3-kinase dependent pathway triggered by TGF-alpha. Finally, we showed
      that GLT-1 is located in non-caveolar lipid rafts of cortical astrocytes. In
      conclusion, this study highlights the occurrence of the reciprocal regulation of
      caveolin and GLT-1 expression during processes such as astrocyte differentiation
      via common signaling pathways. We also provide strong evidence that GLT-1 itself
      is concentrated in lipid rafts, inferring an important role for glial glutamate
      transporter function.

PMID- 15494980
TI  - Cytoprotection against oxidative stress-induced damage of astrocytes by
      extracellular ATP via P2Y1 receptors.
AB  - Oxidative stress is the main cause of neuronal damage in traumatic brain injury,
      hypoxia/reperfusion injury, and neurodegenerative disorders. Although
      extracellular nucleosides, especially adenosine, are well known to protect
      against neuronal damage in such pathological conditions, the effects of these
      nucleosides or nucleotides on glial cell damage remain largely unknown. We report
      that ATP but not adenosine protects against the cell death of cultured astrocytes
      induced by hydrogen peroxide (H2O2). ATP ameliorated the H2O2-induced decrease in
      cell viability of astrocytes in an incubation time- and concentration-dependent
      fashion. Protection by ATP was inhibited by P2 receptor antagonists and was
      mimicked by P2Y1 receptor agonists but not by adenosine. The expressions of P2Y1
      mRNAs and functional P2Y1 receptors in astrocytes were confirmed. Thus, ATP,
      acting on P2Y1 receptors in astrocytes, showed a protective action against H2O2.
      The astrocytic protection by the P2Y1 receptor agonist 2-methylthio-ADP was
      inhibited by an intracellular Ca2+ chelator and a blocker of phospholipase C,
      indicating the involvement of intracellular signals mediated by Gq/11-coupled
      P2Y1 receptors. The ATP-induced protection was inhibited by cycloheximide, a
      protein synthesis inhibitor, and it took more than 12 h for the onset of the
      protective action. In the DNA microarray analysis, ATP induced a dramatic
      upregulation of various oxidoreductase genes. Taken together, ATP acts on P2Y1
      receptors coupled to Gq/11, resulting in the upregulation of oxidoreductase
      genes, leading to the protection of astrocytes against H2O2.

PMID- 15494981
TI  - Increased expression of the astrocytic glutamate transporter GLT-1 in the
      prefrontal cortex of schizophrenics.
AB  - To verify whether altered glial glutamate uptake contributes to the reduced
      efficacy of glutamatergic transmission reported in the prefrontal cortex of
      schizophrenics, we studied the expression of GLT-1, the transporter responsible
      for most glutamate transport, in autoptic samples of prefrontal cortex using real
      time quantitative RT-PCR, immunocytochemistry, and functional assays. GLT-1 mRNA
      levels in medication-free patients were 2.5-fold higher than in controls, whereas
      they were normal or reduced in patients treated with antipsychotics. We also
      observed a 4-fold increase in L-[(3)H]-Glu uptake in Xenopus oocytes injected
      with mRNA from the prefrontal cortex of a medication-free schizophrenic and a 2
      fold increase in GLT-1 protein in the same cortical area of another medication
      free patient. Results suggest that GLT-1 mRNA, protein and function are increased
      in prefrontal cortex of schizophrenics.

PMID- 15494982
TI  - 5-Hydroxytryptamine activates a barium-sensitive, cAMP-mediated potassium
      conductance in the leech giant glial cell.
AB  - 5-Hydroxytryptamine (5-HT), a neurotransmitter and neuromodulator in the central
      nervous system of the leech Hirudo medicinalis hyperpolarizes the giant glial
      cell in the neuropil of segmental ganglia at micromolar concentrations. The 5-HT
      evoked glial response (EC(50) approximately 2.5 microM) is mediated by a non
      desensitizing, G-protein-coupled receptor and due to activation of a Ca(2+)
      independent K(+) conductance. The adenylyl cyclase inhibitor SQ22,536 blocks the
      response to 5-HT; in the presence of 1 mM db-cAMP, but not of 1 mM db-cGMP, the
      glial response is suppressed. The 5-HT-evoked response is reduced by Ba(2+) with
      half-maximal inhibition at 50 microM Ba(2+). The results suggest that release of
      5-HT from serotonergic neurons, or the maintenance of micromolar levels of
      extracellular 5-HT in the ganglion, may help to set the glial membrane potential
      close to the K(+) equilibrium potential.

PMID- 15494983
TI  - NG2 proteoglycan-expressing cells of the adult rat brain: possible involvement in
      the formation of glial scar astrocytes following stab wound.
AB  - Stab wound lesion to the adult central nervous system induces strong
      proliferative response that is followed by the formation of a dense astroglial
      scar. In order to determine the origin of those astrocytes composing the glial
      scar, the cell proliferation marker bromodeoxyuridine (BrdU) was administered to
      lesioned rats that were fixed 3 h or 6 days later. At 3 h after the BrdU
      administration, labeled nuclei were frequently associated with either NG2(+)
      cells or microglia/macrophages, but rarely with astrocytes expressing glial
      fibrillary acidic protein (GFAP). Six days later, by contrast, numerous BrdU
      labeled nuclei were associated with astrocytes located along the lesion borders.
      After the injection of a viral vector of the green fluorescent protein (GFP) into
      the lesional cavity, GFP was preferentially detected within NG2- or GFAP-labeled
      cells when lesioned animals were fixed 1 or 6 days after the injections,
      respectively. The combined detection of glial markers within cells present in the
      lesioned area indicated that, although they rarely express GFAP, the marker of
      mature astrocytes, NG2(+) cells located along the lesion borders frequently
      express nestin and vimentin, i.e., two markers of immature astrocytes. Lastly,
      chronic treatment of lesioned rats with dexamethasone was found to inhibit the
      proliferation of NG2(+) cells present within the lesioned area and to
      subsequently alter the formation of a dense astroglial scar. Taken together,
      these data strongly suggest that following a surgical lesion, at least a portion
      of the astrocytes that constitute the glial scar are issued from resident NG2(+)
      cells.

PMID- 15494984
TI  - Involvement of adenylate cyclase and tyrosine kinase signaling pathways in
      response of crayfish stretch receptor neuron and satellite glia cell to
      photodynamic treatment.
AB  - Neuroglial interactions are most profound during development or damage of nerve
      tissue. We studied the responses of crayfish stretch receptor neurons (SRN) and
      satellite glial cells to photosensitization with sulfonated aluminum
      phthalocyanine Photosens. Although Photosens was localized mainly in the glial
      envelope, neurons were very sensitive to photodynamic treatment.
      Photosensitization gradually inhibited and then abolished neuron activity.
      Neuronal and glial nuclei shrank. Some neurons and glial cells lost the integrity
      of the plasma membrane and died through necrosis after the treatment. The nuclei
      of other glial cells but not neurons become fragmented, indicating apoptosis. The
      number of glial nuclei around neuron soma increased, probably indicating
      proliferation for enhanced neuron protection. Adenylate cyclase (AC) inhibition
      by MDL-12330A, or tyrosine kinase (TK) inhibition by genistein, shortened neuron
      lifetime, whereas AC activation by forskolin or protein tyrosine phosphatases
      (PTP) inhibition by sodium orthovanadate prolonged neuronal activity. Therefore,
      cAMP and phosphotyrosines produced by AC and TK, respectively, protected SRN
      against photoinactivation. AC inhibition reduced photodamage of the plasma
      membrane and subsequent necrosis in neuronal and glial cells. AC activation
      prevented apoptosis in photosensitized glial cells and stimulated glial
      proliferation. TK inhibition protected neurons but not glia against photoinduced
      membrane permeabilization and subsequent necrosis whereas PTP inhibition more
      strongly protected glial cells. Therefore, both signaling pathways involving cAMP
      and phosphotyrosines might contribute to the maintenance of neuronal activity and
      the integrity of the neuronal and glial plasma membranes. Adenylate cyclase but
      not phosphotyrosine signaling pathways modulated glial apoptosis and
      proliferation under photooxidative stress.

PMID- 15494985
TI  - Antipsychotic medication versus placebo for people with both schizophrenia and
      learning disability.
AB  - BACKGROUND: Antipsychotic medication is the standard treatment for people with
      learning disability and schizophrenia. OBJECTIVES: To determine the effects of
      any antipsychotic medication compared with placebo for treating people with a
      dual diagnosis of learning disability and schizophrenia. SEARCH STRATEGY: For
      this update we searched the Cochrane Schizophrenia Group's Register of trials
      (July 2004), relevant reference lists and sought unpublished data from
      pharmaceutical companies. SELECTION CRITERIA: We included all randomised clinical
      trials of longer than one month's duration, involving people with both
      schizophrenia and learning disability (a measured IQ of 70 or less) that
      evaluated antipsychotic medication versus placebo. DATA COLLECTION AND ANALYSIS:
      We reliably selected and assessed studies for methodological quality. Two
      reviewers, working independently, extracted data. We would have analysed
      dichotomous data on an intention-to-treat basis and presented continuous data
      with 65% completion rate. For dichotomous outcomes, our intention was to estimate
      a fixed effect relative risk (RR) with the 95% confidence interval (CI) together
      with the number needed to treat/harm (NNT/H). MAIN RESULTS: We found only one
      relevant randomised trial using our search method and this had to be excluded.
      This study included four people with a dual diagnosis of schizophrenia and
      learning disability, but results were only available for two of the participants.
      It was unclear as to which groups the other two people were allocated. In order
      to display the data, we would have had to have made too many assumptions about
      these two people and any results would be uninformative and potentially
      misleading. REVIEWERS' CONCLUSIONS: Using the methods described we found no
      randomised controlled trial evidence to guide the use of antipsychotic medication
      for people with both learning disability and schizophrenia. Until the urgent need
      for randomised controlled trials is met, clinical practice will continue to be
      guided by extrapolation of evidence from randomised controlled trials involving
      people with schizophrenia, but without learning disability, and non-randomised
      trials of those with learning disability and schizophrenia.

PMID- 15494986
TI  - Antidepressants for smoking cessation.
AB  - BACKGROUND: There are at least two theoretical reasons to believe antidepressants
      might help in smoking cessation. Nicotine withdrawal may produce depressive
      symptoms or precipitate a major depressive episode and antidepressants may
      relieve these. Nicotine may have antidepressant effects that maintain smoking,
      and antidepressants may substitute for this effect. Alternatively, some
      antidepressants may have a specific effect on neural pathways underlying nicotine
      addiction, independent of their antidepressant effects. OBJECTIVES: The aim of
      this review is to assess the effect of antidepressant medications in aiding long
      term smoking cessation. The medications include bupropion; doxepin; fluoxetine;
      imipramine; moclobemide; nortriptyline; paroxetine; sertraline, tryptophan and
      venlafaxine. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group
      trials register which includes trials indexed in MEDLINE, EMBASE, SciSearch and
      PsycINFO, and other reviews and meeting abstracts, in March 2004. SELECTION
      CRITERIA: We considered randomized trials comparing antidepressant medications to
      placebo or an alternative therapy for smoking cessation. We also included trials
      comparing different doses, using pharmacotherapy to prevent relapse or re
      initiate smoking cessation and using pharmacotherapy to help smokers reduce
      cigarette consumption. We excluded trials with less than six months follow up.
      DATA COLLECTION AND ANALYSIS: We extracted data in duplicate on the type of study
      population, the nature of the pharmacotherapy, 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, expressed as an odds ratio (OR). We used the most rigorous
      definition of abstinence for each trial, and biochemically validated rates if
      available. Where appropriate, we performed meta-analysis using a fixed effect
      model. MAIN RESULTS: There was one trial of the monoamine oxidase inhibitor
      moclobemide, and one of the atypical antidepressant venlafaxine. Neither of these
      detected a significant long-term benefit. There were five trials of selective
      serotonin reuptake inhibitors; three of fluoxetine, one of sertraline and one of
      paroxetine. None of these detected significant effects, and there was no evidence
      of a significant benefit when results were pooled. There were 24 trials of
      bupropion and six trials of nortriptyline. When used as the sole pharmacotherapy,
      bupropion (19 trials, OR 2.06, 95% confidence intervals [CI] 1.77 to 2.40) and
      nortriptyline (four trials, OR 2.79, 95% CI 1.70 to 4.59) both doubled the odds
      of cessation. In one trial the combination of bupropion and nicotine patch
      produced slightly higher quit rates than patch alone, but this was not replicated
      in a second study. Two trials of extended therapy with bupropion to prevent
      relapse after initial cessation did not show a significant long-term benefit.
      There is a risk of about 1 in 1000 of seizures associated with bupropion use.
      Concerns that bupropion may increase suicide risk are currently unproven.
      REVIEWERS' CONCLUSIONS: The antidepressants bupropion and nortriptyline aid long
      term smoking cessation but selective serotonin reuptake inhibitors (e.g.
      fluoxetine) do not. The fact that only some forms of antidepressants aid
      cessation and that they do so regardless of depressive symptoms strongly suggests
      that their mode of action is independent of their antidepressant effect.

PMID- 15494987
TI  - Doxapram treatment for apnea in preterm infants.
AB  - BACKGROUND: Recurrent apnea is common in preterm infants, particularly at very
      early gestational ages. These episodes of loss of effective breathing can lead to
      hypoxemia and bradycardia which may be severe enough to require resuscitation
      including use of positive pressure ventilation. Doxapram has been used to
      stimulate breathing and so prevent apnea and its consequences. OBJECTIVES: In
      preterm infants with recurrent apnea, does treatment with Doxapram lead to a
      clinically important reduction in apnea and use of intermittent positive airways
      pressure (IPPV), without clinically important side effects? SEARCH STRATEGY:
      Searches were made of the Oxford Database of Perinatal trials, the Cochrane
      Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3,
      2004), MEDLINE from 1966 - June 2004, EMBASE from 1980 - June 2001, CINAHL from
      1982- June 2004. Text words 'doxapram', 'apnea or apnoea' and the MeSH term
      'infant, premature' were used. Previous reviews including cross references,
      abstracts from conferences and symposia proceedings were also examined. Abstracts
      of the Society for Pediatric Research were searched from 1996 - 2004 inclusive.
      SELECTION CRITERIA: All trials utilising random or quasi-random patient
      allocation, in which doxapram was used for the treatment of apnea in preterm
      infants were included. DATA COLLECTION AND ANALYSIS: Each author evaluated the
      papers for quality and inclusion criteria. Independent data extraction was
      carried out. MAIN RESULTS: Only one trial, which randomized 11 infants to
      intravenous doxapram and 10 infants to placebo, was found. There were fewer
      treatment failures after 48 hours in the group of preterm infants treated with
      doxapram (4/11) compared with the group treated with placebo (8/10). The wide
      confidence intervals made this result non-significant [RR 0.45 (0.20, 1.05)].
      Only one infant, who was from the placebo group, was given IPPV. Of the seven
      responders by 48 hours in the group of 11 who received doxapram, five failed to
      respond between 48 hours and seven days after commencement of therapy. This gives
      a late failure rate of 9/11, similar to the short term failure rate in the
      placebo group of 8/10. It is not possible to evaluate the late responses of all
      those in the placebo group since they crossed over to a treatment arm. REVIEWERS'
      CONCLUSIONS: Although intravenous Doxapram might reduce apnea within the first 48
      hours of treatment, there are insufficient data to evaluate the precision of this
      result or to assess potential adverse effects. No long term outcomes have been
      measured. Further studies are needed to determine the role of this treatment in
      clinical practice.

PMID- 15494988
TI  - Extra-abdominal versus intra-abdominal repair of the uterine incision at
      caesarean section.
AB  - BACKGROUND: Different techniques have been described to reduce morbidity during
      caesarean section. After the baby has been born by caesarean section and the
      placenta has been extracted, temporary removal of the uterus from the abdominal
      cavity (exteriorisation of the uterus) to facilitate repair of the uterine
      incision has been postulated as a valuable technique. This is particularly so
      when exposure of the incision is difficult and when there are problems with
      haemostasis. Several clinical trials have been done, with varying results,
      including substantial reduction in the rate of postoperative infection and
      morbidity with extra-abdominal closure of the uterine incision, and less
      associated peri-operative haemorrhage. Subsequent studies suggest that the method
      of placental removal rather than method of closure of the uterine incision
      influences peri-operative morbidity. OBJECTIVES: To evaluate the effects of extra
      abdominal repair of the uterine incision compared to intra-abdominal repair.
      SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials
      register (September 2003), the Cochrane Central Register of Controlled Trials
      (The Cochrane Library, Issue 3, 2003), MEDLINE (1966 to July 2003) and PubMed
      (1966 to 2003). SELECTION CRITERIA: Randomised controlled trials involving a
      comparison of uterine exteriorisation with intra-abdominal repair of the uterine
      incision in women undergoing caesarean section. DATA COLLECTION AND ANALYSIS: Two
      reviewers independently assessed the trials identified for inclusion. We compared
      categorical data using relative risks and 95% confidence intervals and continuous
      data using the weighted mean difference with 95% confidence intervals. We tested
      for statistical heterogeneity between trials using the I squared test. Where no
      significant heterogeneity (greater than 50%) existed, we pooled data using a
      fixed effect model. If significant heterogeneity existed, a random effects model
      was used. MAIN RESULTS: Six studies were included, with 1294 women randomised
      overall, and 1221 women included in the analysis. There were no statistically
      significant differences between the groups in most of the outcomes identified,
      except for febrile morbidity and length of hospital stay. With extra-abdominal
      closure of the uterine incision, febrile morbidity was lower (relative risk 0.41,
      95% confidence interval (CI) 0.17 to 0.97), and the hospital stay was longer
      (weighted mean difference 0.24 days, 95% CI 0.08 to 0.39). REVIEWERS'
      CONCLUSIONS: There is no evidence from this review to make definitive conclusions
      about which method of uterine closure offers greater advantages, if any. However,
      these results are based on too few and too small studies to detect differences in
      rare, but severe, complications.

PMID- 15494989
TI  - Physician advice for smoking cessation.
AB  - BACKGROUND: Healthcare professionals frequently advise patients to improve their
      health by stopping smoking. Such advice may be brief, or part of more intensive
      interventions. OBJECTIVES: The aims of this review were to assess the
      effectiveness of advice from physicians in promoting smoking cessation; to
      compare minimal interventions by physicians with more intensive interventions; to
      assess the effectiveness of various aids to advice in promoting smoking cessation
      and to determine the effect of anti-smoking advice on disease-specific and all
      cause mortality. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction
      Group trials register and the Cochrane Central Register of Controlled Trials
      (CENTRAL). Date of the most recent searches: March 2004. SELECTION CRITERIA:
      Randomized trials of smoking cessation advice from a medical practitioner in
      which abstinence was assessed at least six months after advice was first
      provided. DATA COLLECTION AND ANALYSIS: We extracted data in duplicate on the
      setting in which advice was given, type of advice given (minimal or intensive),
      and whether aids to advice were used, the outcome measures, method of
      randomization and completeness of follow up. The main outcome measures were
      abstinence from smoking after at least six months follow up and mortality. We
      used the most rigorous definition of abstinence in each trial, and biochemically
      validated rates where available. Subjects lost to follow up were counted as
      smokers. Where possible, meta-analysis was performed using a Mantel-Haenszel
      fixed effect model. MAIN RESULTS: We identified 39 trials, conducted between 1972
      and 2003, including over 31,000 smokers. In some trials, subjects were at risk of
      specified diseases (chest disease, diabetes, ischaemic heart disease), but most
      were from unselected populations. The most common setting for delivery of advice
      was primary care. Other settings included hospital wards and outpatient clinics,
      and industrial clinics. Pooled data from 17 trials of brief advice versus no
      advice (or usual care) revealed a small but significant increase in the odds of
      quitting (odds ratio 1.74, 95% confidence interval 1.48 to 2.05). This equates to
      an absolute difference in the cessation rate of about 2.5%. There was
      insufficient evidence, from indirect comparisons, to establish a significant
      difference in the effectiveness of physician advice according to the intensity of
      the intervention, the amount of follow up provided, and whether or not various
      aids were used at the time of the consultation in addition to providing advice.
      Direct comparison of intensive versus minimal advice showed a small advantage of
      intensive advice (odds ratio 1.44, 95% confidence interval 1.24 to 1.67). Direct
      comparison also suggested a small benefit of follow-up visits. Only one study
      determined the effect of smoking advice on mortality. It found no statistically
      significant differences in death rates at 20 years follow up. REVIEWERS'
      CONCLUSIONS: Simple advice has a small effect on cessation rates. Additional
      manoeuvres appear to have only a small effect, though more intensive
      interventions are marginally more effective than minimal interventions.

PMID- 15494990
TI  - Prophylactic intravenous preloading for regional analgesia in labour.
AB  - BACKGROUND: Reduced uterine blood flow from maternal hypotension may contribute
      to fetal heart rate changes which are common following regional analgesia
      (epidural or spinal or combined spinal-epidural (CSE)) during labour. Intravenous
      fluid preloading may help to reduce maternal hypotension but using lower doses of
      local anaesthetic, and opioid only blocks, may reduce the need for preloading.
      OBJECTIVES: To assess the effects of prophylactic intravenous fluid preloading
      before regional analgesia during labour on maternal and fetal well-being. SEARCH
      STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register
      (19 February 2004). SELECTION CRITERIA: Randomised and quasi-randomised trials
      comparing prophylactic intravenous preloading before regional analgesia during
      labour with a control group (dummy or no preloading). DATA COLLECTION AND
      ANALYSIS: Two reviewers independently applied eligibility criteria, assessed
      trial quality and extracted data. MAIN RESULTS: Six studies are included (473
      participants). In one epidural trial using high-dose local anaesthetic,
      preloading with intravenous fluids was shown to counteract the hypotension which
      frequently follows traditional epidural analgesia (relative risk (RR) 0.07, 95%
      confidence interval (CI) 0.01 to 0.53; 102 women). This trial was also associated
      with a reduction in fetal heart rate abnormalities (RR 0.36, 95% CI 0.16 to 0.83;
      102 women); no differences were detected in other perinatal and maternal outcomes
      for this trial and another high-dose epidural trial. In the two epidural low-dose
      anaesthetic trials, no significant difference in maternal hypotension was found
      (RR 0.73, 95% CI 0.36 to 1.48; 260 women), although they were underpowered to
      detect less than a very large effect. No significant differences were seen
      between groups in these trials for fetal heart rate abnormalities (RR 0.64, 95%
      CI 0.39 to 1.05; 233 women). In the two CSE trials, no differences were reported
      between preloading and no preloading groups. In the spinal/opioid trial, the RR
      for hypotension was 0.89, 95% CI 0.43 to 1.83 (40 women) and 0.70, 95% CI 0.36 to
      1.37 for fetal heart rate abnormalities (32 women). In the opioid only study (30
      women), there were no instances of hypotension or fetal heart rate abnormalities
      in either group. REVIEWERS' CONCLUSIONS: Preloading prior to traditional high
      dose local anaesthetic blocks may have some beneficial fetal and maternal effects
      in healthy women. Low-dose epidural and CSE analgesia techniques may reduce the
      need for preloading. The studies reviewed were too small to show whether
      preloading is beneficial for women having regional analgesia during labour using
      the lower-dose local anaesthetics or opioids. Further investigation of low-dose
      epidural or CSE (including opioid only) blocks, and the risks and benefits of
      intravenous preloading for women with pregnancy complications, is required.

PMID- 15494991
TI  - Ribavirin for respiratory syncytial virus infection of the lower respiratory
      tract in infants and young children.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of lower
      respiratory tract infection in infants and is responsible for 100,000
      hospitalizations annually. Ribavirin is approved for treatment of these
      infections, but its use is controversial because of questions about its efficacy,
      concerns about occupational exposure, and its high cost. OBJECTIVES: The
      objective of this review is to assess the efficacy of aerosolized ribavirin for
      infants and children with lower respiratory tract infection due to RSV. SEARCH
      STRATEGY: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library, Issue 1, 2004), MEDLINE (January 1975 to January
      week 3, 2004) and EMBASE (January 1990 to December 2003). We scanned reference
      lists of articles and contacted experts in the field. SELECTION CRITERIA:
      Randomized trials comparing ribavirin with placebo in infants and children with
      RSV infection and lower respiratory tract infection. DATA COLLECTION AND
      ANALYSIS: Two reviewers independently extracted data and assessed trial quality.
      Unpublished data were requested from authors when necessary. MAIN RESULTS: Twelve
      trials were included. All trials enrolled infants below the age of six months. In
      four trials with 158 patients, mortality with ribavirin was 5.8% compared with
      9.7% with placebo (odds ratio (OR) 0.58; 95% confidence interval (CI) 0.18 to
      1.85). In three trials with 116 patients the probability of respiratory
      deterioration with ribavirin was 7.1% compared with 18.3% with placebo (OR 0.37;
      95% CI 0.12 to 1.18). In three studies with 104 ventilated patients, the weighted
      mean difference in days of hospitalization was 1.9 fewer days with ribavirin (95%
      CI -4.6 to +0.9) and the weighted mean difference in days of ventilation was 1.8
      fewer days with ribavirin (95% CI -3.4 to -0.2). No statistically significant
      differences in long-term pulmonary function or in incidence of recurrent wheezing
      following RSV infection were associated with the use of ribavirin. REVIEWERS'
      CONCLUSIONS: Trials of ribavirin for RSV lack sufficient power to provide
      reliable estimates of the effects. The cumulative results of three small trials
      show that ribavirin may reduce the duration of mechanical ventilation and may
      reduce days of hospitalization. In addition, use of ribavirin may be associated
      with a decrease in the long-term incidence of recurrent wheezing following RSV
      disease. A large randomized controlled trial of ribavirin for ventilated and
      other high-risk patients is indicated.

PMID- 15494992
TI  - Anticoagulants versus antiplatelet therapy for preventing stroke in patients with
      nonrheumatic atrial fibrillation and a history of stroke or transient ischemic
      attack.
AB  - BACKGROUND: People with nonrheumatic atrial fibrillation (NRAF) who have had a
      transient ischemic attack (TIA) or minor ischemic stroke are at risk of recurrent
      stroke. Both warfarin and aspirin have been shown to reduce the recurrence of
      vascular events. OBJECTIVES: The objective of this review was to compare the
      effect of anticoagulants with antiplatelet agents, for secondary prevention, in
      people with NRAF and previous cerebral ischemia. SEARCH STRATEGY: We searched the
      Cochrane Stroke Group trials register (last searched 9 June 2003) and contacted
      trialists. SELECTION CRITERIA: Randomised trials comparing oral anticoagulants
      with antiplatelet agents in patients with NRAF and a previous TIA or minor
      ischemic stroke. DATA COLLECTION AND ANALYSIS: Both reviewers extracted and
      analysed data. MAIN RESULTS: Two trial were identified. The European Atrial
      Fibrillation Trial (EAFT) involving 455 patients, who received either
      anticoagulants (International Normalised Ratio (INR) 2.5 to 4.0), or aspirin (300
      mg/day). Patients joined the trial within three months of transient ischemic
      attack or minor stroke. The mean follow up was 2.3 years. In the Studio Italiano
      Fibrillazione Atriale (SIFA) trial, 916 patients with NRAF and a TIA or minor
      stroke within the previous 15 days were randomised to open label anticoagulants
      (INR 2.0 to 3.5) or indobufen (a reversible platelet cyclooxygenase inhibitor,
      100 or 200 mg BID). The follow-up period was one year. The combined results show
      that anticoagulants were significantly more effective than antiplatelet therapy
      both for all vascular events (Peto odds ratio (Peto OR) 0.67, 95% confidence
      interval (CI) 0.50 to 0.91) and for recurrent stroke (Peto OR 0.49, 95% CI 0.33
      to 0.72). Major extracranial bleeding complications occurred more often in
      patients on anticoagulants (Peto OR 5.16, 95% CI 2.08 to 12.83), but the absolute
      difference was small (2.8% per year versus 0.9% per year in EAFT and 0.9% per
      year versus 0% in SIFA). Warfarin did not cause a significant increase of
      intracranial bleeds. REVIEWERS' CONCLUSIONS: The evidence from two trials
      suggests that anticoagulant therapy is superior to antiplatelet therapy for the
      prevention of stroke in people with NRAF and recent non-disabling stroke or TIA.
      The risk of extracranial bleeding was higher with anticoagulant therapy than with
      antiplatelet therapy.

PMID- 15494993
TI  - Gamma-aminobutyric acid agonists for neuroleptic-induced tardive dyskinesia.
AB  - BACKGROUND: Chronic antipsychotic drug treatment may cause tardive dyskinesia
      (TD), a long-term movement disorder. Gamma-aminobutyric acid (GABA) agonist
      drugs, which have intense sedative properties and may exacerbate psychotic
      symptoms, have been used to treat TD. OBJECTIVES: To determine the effects of
      GABA agonist drugs (baclofen, gamma-vinyl-GABA, gamma-acetylenic-GABA, progabide,
      muscimol, sodium valproate and tetrahydroisoxazolopyridine (THIP)) for people
      with antipsychotic-induced tardive dyskinesia (TD) and schizophrenia or other
      chronic mental illnesses. SEARCH STRATEGY: We updated the previous Cochrane
      review by searching the Cochrane Schizophrenia Group Register (September 2003).
      We searched references for further trial citations and, where possible, contacted
      authors. SELECTION CRITERIA: Randomised controlled trials comparing use of non
      benzodiazepine GABA agonist drugs with placebo or no intervention, involving
      people with schizophrenia or other chronic mental illnesses with signs of
      antipsychotic-induced TD. 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.
      MAIN RESULTS: We identified eight small poorly reported studies for inclusion.
      For the outcome of 'no clinically important improvement in tardive dyskinesia'
      GABA agonist drugs were not clearly better than placebo (n = 108, RR 0.83 CI 0.6
      to 1.1). Deterioration in mental state was more likely to occur in people
      receiving GABA medication (n = 95, RR 2.47 CI 1.1 to 5.4), but this effect was
      influenced by the decision to assign a negative outcome to those who dropped out
      before the end of the study. A greater proportion of people allocated GABA
      medication may fail to complete the trial compared with those allocated placebo
      (20% versus 9%), but this difference was not statistically significant (n = 136,
      RR 1.99 CI 0.8 to 4.7). There is a suggestion of an increase in ataxia (loss of
      power of muscular coordination) for both baclofen and sodium valproate (n = 95,
      RR 3.26 CI 0.4 to 30.2), and in sedation (n = 113, RR 2.12 CI 0.8 to 5.4)
      compared with placebo, but this was not significant. Withdrawal of
      tetrahydroisoxazolopyridine (THIP) may cause seizures. REVIEWERS' CONCLUSIONS:
      Evidence of the effects of baclofen, progabide, sodium valproate, or THIP for
      people with antipsychotic-induced TD is inconclusive and unconvincing. Any
      possible benefits are likely to be outweighed by the adverse effects associated
      with their use.

PMID- 15494994
TI  - Antibiotics for acute bronchitis.
AB  - BACKGROUND: Antibiotic treatment of acute bronchitis, which is one of the most
      common illnesses seen in primary care, is controversial. Most clinicians
      prescribe antibiotics in spite of expert recommendations against this practice.
      OBJECTIVES: The objective of this review was to assess the effects of antibiotic
      treatment for patients with a clinical diagnosis of acute bronchitis. SEARCH
      STRATEGY: In this updated review, we searched the Cochrane Central Register of
      Controlled trials (CENTRAL) (The Cochrane Library Issue 2, 2004); MEDLINE
      (January 1966 to March 2004); EMBASE (January 2000 to December 2003); SciSearch
      from 1989 to 2004; reference lists of articles and the authors' personal
      collections up to 1996, and also wrote to study authors and drug manufacturers.
      EMBASE has previously been searched from 1974 to 2000). SELECTION CRITERIA:
      Randomised controlled trials comparing any antibiotic therapy with placebo in
      acute bronchitis or acute productive cough without other obvious cause in
      patients without underlying pulmonary disease. DATA COLLECTION AND ANALYSIS: At
      least two reviewers extracted data and assessed trial quality. Authors were
      contacted for missing data. MAIN RESULTS: Nine trials involving over 750 patients
      aged eight to over 65 and including smokers and non-smokers were included in the
      primary analysis. The quality of the trials was variable. A variety of outcome
      measures were assessed. Overall, patients receiving antibiotics had better
      outcomes than did those receiving placebo. At a follow-up visit, they were less
      likely to have a cough (relative risk (RR) 0.64, 95% confidence interval (CI)
      0.49 to 0.85; number-needed-to-treat (NNT) 5; 95% CI 3 to 14), show no
      improvement on physician assessment (RR 0.52; 95% CI 0.31 to 0.87; NNT 14; 95% CI
      8 to 50), or have abnormal lung findings (RR 0.48; 95% CI 0.26 to 0.89; NNT 11;
      95% CI 6 to 50); and had shorter durations of cough (weighted mean difference
      0.58 days; 95% CI 0.01 to 1.16 days), productive cough (weighted mean difference
      (WMD) 0.52 days; 95% CI 0.01 to 1.03 days), and feeling ill (WMD 0.58 days; 95%
      CI 0.00 to 1.16 days). There were no significant differences regarding the
      presence of night cough, productive cough, or activity limitations at follow up,
      or in the mean duration of activity limitations. The benefits of antibiotics were
      less apparent in a sensitivity analysis that included data from two other studies
      of patients with upper respiratory tract infections with productive cough. There
      was a non significant trend towards an increase in adverse effects in the
      antibiotic group, relative risk (RR) 1.22 (95% CI 0.94 to 1.58). REVIEWERS'
      CONCLUSIONS: Overall, antibiotics appear to have a modest beneficial effect in
      patients who are diagnosed with acute bronchitis. The magnitude of this benefit,
      however, is similar to that of the detriment from potential adverse effects.

PMID- 15494995
TI  - Back schools for non-specific low-back pain.
AB  - BACKGROUND: Since the introduction of the Swedish back school in 1969, back
      schools have frequently been used for treating patients with low-back pain (LBP).
      However, the content of back schools has changed and appears to vary widely
      today. OBJECTIVES: To assess the effectiveness of back schools for patients with
      non-specific LBP. SEARCH STRATEGY: We searched the MEDLINE and EMBASE databases
      and the Cochrane Central Register of Controlled Trials to May 2003 for relevant
      trials reported in English, Dutch, French or German. We also screened references
      from relevant reviews and included trials. SELECTION CRITERIA: Randomized
      controlled trials (RCTs) that reported on any type of back school for non
      specific LBP were included. DATA COLLECTION AND ANALYSIS: Four reviewers, blinded
      to authors, institution and journal, independently extracted the data and
      assessed the quality of the trials. We set the high quality level, a priori, at a
      trial meeting six or more of 11 internal validity criteria. As data were
      clinically and statistically too heterogeneous to perform a meta-analysis, we
      used a qualitative review (best evidence synthesis) to summarize the results. The
      evidence was classified into four levels (strong, moderate, limited or no
      evidence), taking into account the methodological quality of the studies. We also
      evaluated the clinical relevance of the studies. MAIN RESULTS: Nineteen RCTs
      (3584 patients) were included in this updated review. Overall, the methodological
      quality was low, with only six trials considered to be high quality. It was not
      possible to perform relevant subgroup analyses for LBP with radiation versus LBP
      without radiation. The results indicate that there is moderate evidence
      suggesting that back schools have better short and intermediate-term effects on
      pain and functional status than other treatments for patients with recurrent and
      chronic LBP. There is moderate evidence suggesting that back schools for chronic
      LBP in an occupational setting, are more effective than other treatments and
      placebo or waiting list controls on pain, functional status and return to work
      during short and intermediate-term follow-up. In general, the clinical relevance
      of the studies was rated as insufficient. REVIEWERS' CONCLUSIONS: There is
      moderate evidence suggesting that back schools, in an occupational setting,
      reduce pain, and improve function and return-to-work status, in the short and
      intermediate-term, compared to exercises, manipulation, myofascial therapy,
      advice, placebo or waiting list controls, for patients with chronic and recurrent
      LBP. However, future trials should improve methodological quality and clinical
      relevance and evaluate the cost-effectiveness of back schools.

PMID- 15494996
TI  - Synchronized mechanical ventilation for respiratory support in newborn infants.
AB  - BACKGROUND: During synchronized mechanical ventilation, positive airway pressure
      and spontaneous inspiration coincide. Thus, if synchronous ventilation is
      provoked, adequate gas exchange should be achieved at lower peak airway
      pressures, potentially reducing barotrauma and hence airleak and chronic lung
      disease. Synchronous ventilation can be achieved by manipulation of rate and
      inspiratory time during conventional ventilation and employment of patient
      assisted ventilation. OBJECTIVES: To compare (i) the efficacy of synchronized
      mechanical ventilation, delivered as high frequency positive pressure ventilation
      or triggered ventilation (patient triggered ventilation (PTV) or synchronous
      intermittent mandatory ventilation (SIMV)) with conventional ventilation(ii)
      different types of triggered ventilation SEARCH STRATEGY: Searches from 1985-2004
      of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane
      Library, Issue 3, 2004), Oxford Database of Perinatal Trials, MEDLINE, previous
      reviews, abstracts and symposia proceedings; hand searches of journals in the
      English language and contact with expert informants. SELECTION CRITERIA:
      Randomized or quasi randomized clinical trials comparing synchronized ventilation
      delivered as high frequency positive pressure ventilation (HFPPV) or triggered
      ventilation (PTV/SIMV) to conventional mechanical ventilation (CMV) in neonates.
      Randomized trials comparing different triggered ventilation modes (PTV and SIMV)
      in neonates. DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes
      including mortality, airleaks (pneumothorax or pulmonary interstitial emphysema
      (PIE)), severe intracerebral haemorrhage (grades 3 and 4), chronic lung disease
      (oxygen dependency beyond 28 days) and duration of weaning/ventilation. Three
      comparisons were made: (i) HFPPV vs CMV; (ii) PTV/SIMV vs CMV; (iii) PTV vs SIMV.
      Data analysis was conducted using relative risk for categorical outcomes,
      weighted mean difference for outcomes measured on a continuous scale. MAIN
      RESULTS: Eleven studies were eligible for inclusion. The meta-analysis
      demonstrate that HFPPV compared to CMV was associated with a reduction in the
      risk of airleak (typical relative risk for pneumothorax was 0.69, 95% CI 0.51,
      0.93). PTV/SIMV compared to CMV was associated with a shorter duration of
      ventilation (weighted mean difference -34.8 hours, 95% CI -62.1, -7.4). PTV
      compared to SIMV was associated with a trend to a shorter duration of weaning
      (weighted mean difference -42.4 hours, 95% CI -94.4, 9.6). Neither HFPPV nor
      triggered ventilation was associated with a significant reduction in the
      incidence of chronic lung disease. There was a non-significant trend towards a
      lower mortality rate using HFPPV versus CMV, but a non-significant trend towards
      a higher mortality rate using triggered ventilation versus CMV. No disadvantage
      of HFPPV or triggered ventilation was noted regarding other outcomes. REVIEWERS'
      CONCLUSIONS: Compared to conventional ventilation, benefit is demonstrated for
      both HFPPV and triggered ventilation with regard to a reduction in airleak and a
      shorter duration of ventilation, respectively. In none of the trials was complex
      respiratory monitoring undertaken and thus it is not possible to conclude that
      the mechanism of producing those benefits is by provocation of synchronized
      ventilation. Further trials are needed to determine whether synchronized
      ventilation is associated with other benefits, but optimization of trigger and
      ventilator design with respect to respiratory diagnosis is encouraged before
      embarking on further trials.

PMID- 15494997
TI  - Circulatory volume expansion therapy for aneurysmal subarachnoid haemorrhage.
AB  - BACKGROUND: Secondary ischaemia is a frequent complication after aneurysmal
      subarachnoid haemorrhage (SAH), and responsible for a substantial proportion of
      patients with poor outcome after SAH. The cause of secondary ischaemia is
      unknown, but hypovolaemia and fluid restriction are important risk factors.
      Therefore, volume expansion therapy (hypervolaemia) is frequently used in
      patients with SAH to prevent or treat secondary ischaemia. OBJECTIVES: To
      determine the effectiveness of volume expansion therapy for improving outcome in
      patients with aneurysmal SAH. SEARCH STRATEGY: We searched the Cochrane Stroke
      Group Trials Register (last searched September 2003). In addition we searched
      MEDLINE (1966 to January 2004) and EMBASE (1980 to January 2004) and contacted
      trialists to identify further published and unpublished studies. SELECTION
      CRITERIA: All randomised controlled trials of volume expansion therapy in
      patients with aneurysmal SAH. We also sought controlled trials based on
      consecutive groups of patients quasi-randomly allocated to treatment or control
      group and included these in the analysis if the two groups were well comparable
      with regard to major prognostic factors. DATA COLLECTION AND ANALYSIS: Two
      reviewers independently extracted the data and assessed trial quality. Trialists
      were contacted to obtain missing information. MAIN RESULTS: We identified three
      trials. One truly randomised trial and one quasi-randomised trial with comparable
      baseline characteristics for both groups were included in the analyses. Volume
      expansion therapy did not improve outcome (Relative Risk (RR) 1.0; 95% Confidence
      Interval (CI) 0.5 to 2.2), nor the occurrence of secondary ischaemia (RR 1.1; 95%
      CI 0.5 to 2.2). Hypervolaemia tended to increase the rate of complications (RR
      1.8; 95% CI 0.9 to 3.7) In another quasi-randomised trial, outcome assessment was
      done only at the day of operation (7 to 10 days after SAH). In the period before
      operation, treatment resulted in a reduction of secondary ischaemia (RR 0.33; 95%
      CI 0.11 to 0.99) and case fatality (RR 0.20; 95% CI 0.07 to 1.2). REVIEWERS'
      CONCLUSIONS: The effects of volume expansion therapy have been studied properly
      in only two trials of patients with aneurysmal SAH, with very small numbers. At
      present, there is no sound evidence for the use of volume expansion therapy in
      patients with aneurysmal SAH.

PMID- 15494998
TI  - Thrombolysis (different doses, routes of administration and agents) for acute
      ischaemic stroke.
AB  - BACKGROUND: Thrombolytic therapy is effective for acute myocardial infarction, a
      disease with some similarities to acute ischaemic stroke. Meta-analyses suggest a
      net benefit in acute ischaemic stroke. OBJECTIVES: To assess different
      thrombolytic agents, and different regimens, in acute ischaemic stroke. SEARCH
      STRATEGY: We searched the Cochrane Stroke Group trials register (last searched to
      June 2003), MEDLINE (1966 to July 2003) and EMBASE (1980 to July 2003). We
      handsearched four Japanese journals, contacted researchers and pharmaceutical
      companies, and attended relevant conferences. SELECTION CRITERIA: Randomised and
      quasi-randomised trials of different doses of a thrombolytic agent, or different
      agents, or the same agent given by different routes, in people with confirmed
      acute ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two reviewers independently
      assessed trial eligibility and quality, and extracted the data. MAIN RESULTS: Ten
      trials involving 1641 patients, 8 conducted in Japan, 1 in China and 1 in the
      USA, were included. Concealment of allocation was poorly described. Different
      doses (of tissue plasminogen activator or urokinase) were compared in seven
      trials (n = 1072 patients). Different agents (tissue plasminogen activator versus
      urokinase; tissue-cultured urokinase versus conventional urokinase) were compared
      in three trials (n = 688 patients). One trial compared different routes of
      administration (intravenous plus intraarterial tissue plasminogen activator
      versus intraarterial tissue plasminogen activator alone, n = 35 patients). As
      some trials compared different agents and different doses, some patients
      contributed to two analyses. A higher dose of thrombolytic therapy was associated
      with a three-fold increase in fatal intracranial haemorrhages (Odds ratio (OR)
      3.25, 95% confidence interval (CI) 1.32 to 7.97) compared with a lower dose of
      the same agent (based on 16 events among 539 higher-dose patients and 4 events
      among 533 lower-dose patients in 7 trials). There was no statistically
      significant difference in early (OR 1.01, 95% CI 0.58 to 1.74) or late (OR 0.94,
      95% CI 0.58 to 1.53) deaths between lower and higher doses. Data were inadequate
      to assess the effect of dose on functional outcome. No statistically significant
      difference was shown between different thrombolytic agents tested. The data from
      the pilot trial comparing different routes of administration were inconclusive.
      REVIEWERS' CONCLUSIONS: These scant data suggest that higher doses of
      thrombolytic agents may lead to higher rates of bleeding. However, the evidence
      is inadequate to conclude whether lower doses of thrombolytic agents are more
      effective than higher doses, or whether one agent is better than another, or
      which route of administration is the best, in acute ischaemic stroke.

PMID- 15494999
TI  - Anaesthesia for hip fracture surgery in adults.
AB  - BACKGROUND: The majority of people with hip fracture are treated surgically,
      requiring anaesthesia. OBJECTIVES: To compare different types of anaesthesia for
      surgical repair of hip fractures (proximal femoral fractures) in adults. SEARCH
      STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group specialised
      register (November 2003), MEDLINE (1996 to February week 2 2004), EMBASE (1988 to
      2004 week 10) and reference lists of relevant articles. SELECTION CRITERIA:
      Randomised and quasi-randomised trials comparing different methods of anaesthesia
      for hip fracture surgery in adults. The primary focus of this review was the
      comparison of regional (spinal or epidural) anaesthesia versus general
      anaesthesia. The use of nerve blocks preoperatively or in conjunction with
      general anaesthesia is evaluated in another review. The primary outcome was
      mortality. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed
      trial quality and extracted data. MAIN RESULTS: Twenty two trials, involving 2567
      predominantly female and elderly patients, comparing regional anaesthesia with
      general anaesthesia were included. All trials had methodological flaws and many
      do not reflect current anaesthetic practice. Pooled results from eight trials
      showed regional anaesthesia to be associated with a decreased mortality at one
      month (56/811 (6.9%) versus 86/857 (10.0%)); however, this was of borderline
      statistical significance (relative risk (RR) 0.69, 95% confidence interval (CI)
      0.50 to 0.95). The results from six trials for three month mortality were not
      statistically significant, although the confidence interval does not exclude the
      possibility of a clinically relevant reduction (86/726 (11.8%) versus 98/765
      (12.8%), RR 0.92, 95% CI 0.71 to 1.21). The reduced numbers of trial participants
      at one year, coming exclusively from two trials, preclude any useful conclusions
      for long-term mortality (80/354 (22.6%) versus 78/372 (21.0%), RR 1.07, 95% CI
      0.82 to 1.41).Regional anaesthesia was associated with a reduced risk of deep
      venous thrombosis (39/129 (30%) versus 61/130 (47%); RR 0.64, 95% CI 0.48 to
      0.86). However, this finding is insecure due to possible selection bias in the
      subgroups in whom this outcome was measured. Regional anaesthesia was also
      associated with a reduced risk of acute postoperative confusion (11/117 (9.4%)
      versus 23/120 (19.2%), RR 0.50, 95% CI 0.26 to 0.95). There was insufficient
      evidence to draw any conclusions from a further four included trials, involving a
      total of 179 participants, which compared other methods of anaesthesia (a 'light'
      general with spinal anaesthesia; intravenous ketamine; nerve blocks). REVIEWERS'
      CONCLUSIONS: Overall, there was insufficient evidence available from trials
      comparing regional versus general anaesthesia to rule out clinically important
      differences. Regional anaesthesia may reduce acute postoperative confusion but no
      conclusions can be drawn for mortality or other outcomes.

PMID- 15495000
TI  - Cognitive behaviour therapy for schizophrenia.
AB  - BACKGROUND: Cognitive behavioural therapy (CBT) is now a recommended treatment
      for people with schizophrenia. This approach helps to link the person's feelings
      and patterns of thinking which underpin distress. OBJECTIVES: To review the
      effects of CBT for people with schizophrenia when compared to standard care,
      specific medication, other therapies and no intervention. SEARCH STRATEGY: This
      2004 update built on past work by searching the Cochrane Schizophrenia Groups'
      Register of Trials (January 2004). We inspected all references of the selected
      articles for further relevant trials. SELECTION CRITERIA: All relevant clinical
      randomised trials of cognitive behaviour therapy for people with schizophrenia
      like illnesses. DATA COLLECTION AND ANALYSIS: Studies were reliably selected and
      assessed for methodological quality. Two reviewers, working independently,
      extracted data. We analysed dichotomous data on an intention-to-treat basis and
      continuous data with 65% completion rate are presented. Where possible, for
      dichotomous outcomes, we estimated a relative risk (RR) with the 95% confidence
      interval (CI) along with the number needed to treat/harm (NNT/H). MAIN RESULTS:
      30 papers described 19 trials. CBT plus standard care did not reduce relapse and
      readmission compared with standard care (long term 4 RCTs, n=357, RR 0.8 CI 0.5
      to 1.5), but did decrease the risk of staying in hospital (1 RCT, n=62, RR 0.5 CI
      0.3 to 0.9, NNT 4 CI 3 to 15). CBT helped mental state over the medium term (2
      RCTs, n=123, RR No meaningful improvement 0.7 CI 0.6 to 0.9, NNT 4 CI 3 to 9) but
      after one year the difference was gone (3 RCTs, n=211, RR 0.95 CI 0.6 to 1.5).
      Continuous measures of mental state (BDI, BPRS, CPRS, MADRS, PAS) do not
      demonstrate a consistent effect. When compared with supportive psychotherapy, CBT
      had no effect on relapse (1 RCT, n=59, RR medium term 0.6 CI 0.2 to 2; 2 RCTs,
      n=83, RR long term 1.1 CI 0.5 to 2.4). This also applies to the outcome of 'No
      clinically meaningful improvements in mental state' over the same time periods (1
      RCT, n=59, RR medium term 0.8 CI 0.6 to 1.1; 2 RCT, n=100, RR long term 0.9 CI
      0.8 to 1.1). When CBT was combined with a psychoeducational approach there was no
      significant reduction of readmission rates relative to standard care alone (1
      RCT, n=91, RR 0.9 CI 0.6 to 1.4). REVIEWERS' CONCLUSIONS: CBT is a promising but
      under evaluated intervention. Currently, trial-based data supporting the wide use
      of CBT for people with schizophrenia or other psychotic illnesses are far from
      conclusive. More trials are justified, especially in comparison with a lower
      grade supportive approach. These trials should be designed to be both clinically
      meaningful and widely applicable.

PMID- 15495001
TI  - Colloids versus crystalloids for fluid resuscitation in critically ill patients.
AB  - BACKGROUND: Colloid solutions are widely used in fluid resuscitation of
      critically ill patients. There are several choices of colloid and there is
      ongoing debate about the relative effectiveness of colloids compared to
      crystalloid fluids. OBJECTIVES: To assess the effects on mortality of colloids
      compared to crystalloids for fluid resuscitation in critically ill patients.
      SEARCH STRATEGY: We searched the Injuries Group specialised register, Cochrane
      Controlled Trials Register, MEDLINE, EMBASE and BIDS Index to Scientific and
      Technical Proceedings, and checked reference lists of trials and review articles.
      SELECTION CRITERIA: All randomised and quasi-randomised trials of colloids
      compared to crystalloids, in patients requiring volume replacement. Cross-over
      trials and trials in pregnant women and neonates were excluded. DATA COLLECTION
      AND ANALYSIS: Two reviewers independently extracted data and rated quality of
      allocation concealment. Trials with a 'double-intervention', such as those
      comparing colloid in hypertonic crystalloid to isotonic crystalloid, were
      analysed separately. The analysis was stratified according to colloid type and
      quality of allocation concealment. MAIN RESULTS: Colloids compared to
      crystalloidsAlbumin or plasma protein fraction. Nineteen trials reported data on
      mortality, including a total of 7576 patients. The pooled relative risk (RR) from
      these trials was 1.02 (95% confidence interval [95% CI] 0.93 to 1.11). When the
      trial with poor quality allocation concealment was excluded, pooled RR was 1.01
      (95% CI 0.92 to 1.10). Hydroxyethyl starch. Ten trials compared hydroxyethyl
      starch with crystalloids, including a total of 374 randomised participants. The
      pooled RR was 1.16 (95% CI 0.68 to 1.96). Modified gelatin. Seven trials compared
      modified gelatin with crystalloid, including a total of 346 randomised
      participants. The pooled RR was 0.54 (95% CI 0.16 to 1.85). Dextran. Nine trials
      compared dextran with a crystalloid, including a total of 834 randomised
      participants. The pooled relative risk was RR 1.24 (95% CI 0.94 to 1.65).
      Colloids in hypertonic crystalloid compared to isotonic crystalloidEight trials
      compared dextran in hypertonic crystalloid with isotonic crystalloid, including
      1283 randomised participants. Pooled RR was 0.88 (95% CI 0.74 to 1.05).
      REVIEWERS' CONCLUSIONS: There is no evidence from randomised controlled trials
      that resuscitation with colloids reduces the risk of death, compared to
      resuscitation with crystalloids, in patients with trauma, burns or following
      surgery. As colloids are not associated with an improvement in survival, and as
      they are more expensive than crystalloids, it is hard to see how their continued
      use in these patients can be justified outside the context of randomised
      controlled trials.

PMID- 15495002
TI  - Vitamin C for preventing and treating the common cold.
AB  - BACKGROUND: The role of oral vitamin C (ascorbic acid) in the prevention and
      treatment of the common cold has been a subject of controversy for at least sixty
      years. Public interest in the topic continues to be high and vitamin C continues
      to be widely sold and used as a preventive and therapeutic agent for this common
      ailment. OBJECTIVES: To discover whether oral vitamin C in doses of 200 mg or
      more daily, reduces the incidence, duration or severity of the common cold when
      used either as continuous prophylaxis or after the onset of cold symptoms. SEARCH
      STRATEGY: This updated review added to earlier searches, a full search of the
      following electronic databases: the Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library Issue 2, 2004); MEDLINE (January 1966 to June
      2004); and EMBASE (1990 to June 2004). SELECTION CRITERIA: Papers were excluded
      if a dose less than 200 mg daily of vitamin C was used; if there was no placebo
      comparison; if methods of outcome assessment were inadequately described; and if
      the report did not record any of the three study outcomes (incidence, duration or
      severity) in sufficient detail to enter into the meta-analysis. Three criteria of
      study quality were assessed: Jadad scores, placebo distinguish-ability, and
      allocation concealment. DATA COLLECTION AND ANALYSIS: Two reviewers independently
      extracted data and assessed trial quality. 'Incidence' of colds during
      prophylaxis was assessed as the proportion of participants experiencing one or
      more colds during the study period. 'Duration' was the mean days of illness of
      cold episodes and 'severity' of these episodes was assessed by days confined
      indoors, off work or school. or by symptom severity scores. MAIN RESULTS: Twenty
      nine trial comparisons involving 11,077 study participants contributed to the
      meta-analysis on the relative risk (RR) of developing a cold while taking
      prophylaxis. The pooled RR was 0.96 (95% CI 0.92 to 1.00). A subgroup of six
      trials that involved a total of 642 marathon runners, skiers, and soldiers on sub
      arctic exercises reported a pooled RR of 0.50 (95%CI 0.38 to 0.66). Thirty
      comparisons that involved 9,676 respiratory episodes contributed to the meta
      analysis on common cold duration during prophylaxis . A consistent benefit was
      observed, representing a reduction in cold duration of 8% (95% CI 3% to 13%) for
      adult participants and 13.5% (95% CI 5% to 21%) for child participants. Fifteen
      trial comparisons that involved 7,045 respiratory episodes contributed to the
      meta-analysis of severity of episodes experienced while on prophylaxis. The
      pooled results revealed a difference favouring those on vitamin C when days
      confined to home and off work or school were taken as a measure of severity (p =
      0.02), and when restricting to studies which used symptom severity scores (p =
      0.16), and for the both measures of severity combined (p = 0.004). Seven trial
      comparisons that involved 3,294 respiratory episodes contributed to the meta
      analysis of cold duration during therapy with vitamin C that was initiated after
      the onset of cold symptoms, and no significant difference from placebo was seen.
      Four trial comparisons that involved 2,753 respiratory episodes, contributed to
      the meta-analysis of cold severity during therapy and no significant difference
      from placebo was seen.In laboratory studies, differing methods of artificial
      transmission of virus to vitamin C or placebo treated volunteers in residential
      experiments gave different results. Volunteers infected by nasal installation
      showed small or no benefit from vitamin C, whereas a group who were infected more
      naturally, reported less severe symptom severity scores (p = 0.04). REVIEWERS'
      CONCLUSIONS: The failure of vitamin C supplementation to reduce the incidence of
      colds in the normal population indicates that routine mega-dose prophylaxis is
      not rationally justified for community use. But evidence shows that it could be
      justified in persons exposed to brief periods of severe physical exercise and/or
      cold environments. Also, the consistent and statistically significant small
      benefits on duration and severity for those using regular vitamin C prophylaxis
      indicates that vitamin C plays some role in respiratory defence mechanisms. The
      trials in which vitamin C was introduced at the onset of colds as therapy did not
      show any benefit in doses up to 4 grams daily, but one large trial reported
      equivocal benefit from an 8 gram therapeutic dose at onset of symptoms.

PMID- 15495003
TI  - Therapeutic hypothermia for head injury.
AB  - BACKGROUND: Induced hypothermia has been used in the treatment of head injury for
      many years. Encouraging results from small trials and laboratory studies led to
      renewed interest in the area and some larger trials. OBJECTIVES: To estimate the
      effects of mild induced hypothermia in moderate and severe head injury on
      mortality, long-term functional outcome, complications, and short-term control of
      intracranial pressure (ICP). SEARCH STRATEGY: We searched the Injuries Group
      Specialised register (last searched in 2001), MEDLINE, EMBASE and the Cochrane
      Controlled Trials Register. We handsearched conference proceedings and checked
      reference lists of relevant articles, including a systematic review published in
      2003. SELECTION CRITERIA: Randomised controlled trials of mild hypothermia to 34
      35 masculine Celsius for at least 12 hours versus control (open or normothermia)
      in patients with any closed head injury requiring hospitalisation. Two reviewers
      independently assessed all trials. DATA COLLECTION AND ANALYSIS: Data on death,
      Glasgow outcome scale, complications and ICP were sought and extracted, either
      from published material or by contacting the investigators. Odds ratios (ORs) and
      95% confidence intervals (CIs) were calculated for each trial on an intention-to
      treat basis. Quantitative synthesis of data on complications other than pneumonia
      or ICP was not attempted. Trials of immediate and deferred hypothermia were
      analysed separately. MAIN RESULTS: We found 14 trials with 1094 participants.
      Active immediate hypothermia was associated with an OR for death of 0.80, (1061
      patients, OR 0.80, 95% CI 0.61 to 1.04), and 0.75 for odds of being dead or
      severely disabled, (746 patients, OR 0.75, 95% CI 0.56 to 1.00). Hypothermia
      treatment was associated with a statistically significant increase in odds of
      pneumonia (281 patients, OR 1.95, 95% CI 1.18 to 3.23). The trial of deferred
      hypothermia (33 patients) reported a huge but not statistically significant
      reduction in the odds of death at six months, (OR 0.21, 95% CI 0.04 to 1.05). For
      death or severe disability, deferred hypothermia was associated with an OR of
      0.10 (95% CI 0.01 to 1.00). REVIEWERS' CONCLUSIONS: There is no evidence that
      hypothermia is beneficial in the treatment of head injury. The earlier,
      encouraging, trial results have not been repeated in larger trials. The reasons
      for this are unclear. Hypothermia increases the risk of pneumonia and has other
      potentially harmful side-effects. Therefore, it would seem inappropriate to use
      this intervention outside of controlled trials in subgroups of patients for whom
      there is good reason to think the treatment would be beneficial.

PMID- 15495004
TI  - Interventions for promoting smoking cessation during pregnancy.
AB  - BACKGROUND: Smoking remains one of the few potentially preventable factors
      associated with low birthweight, preterm birth and perinatal death. OBJECTIVES:
      To assess the effects of smoking cessation programs implemented during pregnancy
      on the health of the fetus, infant, mother, and family. SEARCH STRATEGY: We
      searched the Cochrane Pregnancy and Childbirth Group trials register and the
      Cochrane Tobacco Addiction Group trials register (July 2003), MEDLINE (January
      2002 to July 2003), EMBASE (January 2002 to July 2003), PsychLIT (January 2002 to
      July 2003), CINAHL (January 2002 to July 2003), and AUSTHEALTH (January 2002 to
      2003). We contacted trial authors to locate additional unpublished data. We
      handsearched references of identified trials and recent obstetric journals.
      SELECTION CRITERIA: Randomised and quasi-randomised trials of smoking cessation
      programs implemented during pregnancy. DATA COLLECTION AND ANALYSIS: Four
      reviewers assessed trial quality and extracted data independently. MAIN RESULTS:
      This review included 64 trials. Fifty-one randomised controlled trials (20,931
      women) and six cluster-randomised trials (over 7500 women) provided data on
      smoking cessation and/or perinatal outcomes. Despite substantial variation in the
      intensity of the intervention and the extent of reminders and reinforcement
      through pregnancy, there was an increase in the median intensity of both 'usual
      care' and interventions over time. There was a significant reduction in smoking
      in the intervention groups of the 48 trials included: (relative risk (RR) 0.94,
      95% confidence interval (CI) 0.93 to 0.95), an absolute difference of six in 100
      women continuing to smoke. The 36 trials with validated smoking cessation had a
      similar reduction (RR 0.94, 95% CI 0.92 to 0.95). Smoking cessation interventions
      reduced low birthweight (RR 0.81, 95% CI 0.70 to 0.94) and preterm birth (RR
      0.84, 95% CI 0.72 to 0.98), and there was a 33 g (95% CI 11 g to 55 g) increase
      in mean birthweight. There were no statistically significant differences in very
      low birthweight, stillbirths, perinatal or neonatal mortality but these analyses
      had very limited power. One intervention strategy, rewards plus social support
      (two trials), resulted in a significantly greater smoking reduction than other
      strategies (RR 0.77, 95% CI 0.72 to 0.82). Five trials of smoking relapse
      prevention (over 800 women) showed no statistically significant reduction in
      relapse. REVIEWERS' CONCLUSIONS: Smoking cessation programs in pregnancy reduce
      the proportion of women who continue to smoke, and reduce low birthweight and
      preterm birth. The pooled trials have inadequate power to detect reductions in
      perinatal mortality or very low birthweight.

PMID- 15495005
TI  - Antibiotic regimens for endometritis after delivery.
AB  - BACKGROUND: Postpartum endometritis, which is more common after cesarean section,
      occurs when vaginal organisms invade the endometrial cavity during labor and
      birth. Antibiotic treatment is warranted. OBJECTIVES: The effect of different
      antibiotic regimens for the treatment of postpartum endometritis on failure of
      therapy and complications was systematically reviewed. SEARCH STRATEGY: We
      searched the Cochrane Pregnancy and Childbirth Group's trials register (30
      January 2004). SELECTION CRITERIA: Randomized trials of different antibiotic
      regimens for postpartum endometritis, after cesarean section or vaginal birth,
      where outcomes of treatment failure or complications were reported were selected.
      DATA COLLECTION AND ANALYSIS: We abstracted data independently and made
      comparisons between different types of antibiotic regimen based on type of
      antibiotic and duration and route of administration. Summary relative risks were
      calculated. MAIN RESULTS: Thirty-eight trials with 3983 participants were
      included. Fifteen studies comparing clindamycin and an aminoglycoside with
      another regimen showed more treatment failures with the other regimen (relative
      risk (RR) 1.44; 95% confidence interval (CI) 1.15 to 1.80). Failures of those
      regimens with poor activity against penicillin resistant anaerobic bacteria were
      more likely (RR 1.94; 95% CI 1.38 to 2.72). In three studies that compared
      continued oral antibiotic therapy after intravenous therapy with no oral therapy,
      no differences were found in recurrent endometritis or other outcomes. In four
      studies comparing once daily with thrice daily dosing of gentamicin there were
      fewer failures with once daily dosing. There was no evidence of difference in
      incidence of allergic reactions. Cephalosporins were associated with less
      diarrhea. REVIEWERS' CONCLUSIONS: The combination of gentamicin and clindamycin
      is appropriate for the treatment of endometritis. Regimens with activity against
      penicillin- resistant anaerobic bacteria are better than those without. There is
      no evidence that any one regimen is associated with fewer side effects. Once
      uncomplicated endometritis has clinically improved with intravenous therapy, oral
      therapy is not needed.

PMID- 15495006
TI  - Crisis intervention for people with severe mental illnesses.
AB  - BACKGROUND: A particularly difficult challenge for community treatment of people
      with serious mental illnesses is the delivery of an acceptable level of care
      during the acute phases of severe mental illness. Crisis intervention models of
      care were developed as a possible solution. OBJECTIVES: To review the effects of
      a crisis intervention model for anyone with serious mental illness experiencing
      an acute episode, compared to 'standard care'. SEARCH STRATEGY: Searches of 1998
      were updated with a search of the Cochrane Schizophrenia Group's Register of
      trials (July 2003). SELECTION CRITERIA: All randomised controlled trials of
      crisis intervention models versus standard care for people with severe mental
      illnesses. DATA COLLECTION AND ANALYSIS: Working independently, reviewers
      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.
      MAIN RESULTS: This 2003 update includes no new studies. Five studies, none purely
      investigating crisis intervention, are included and 21 excluded. All included
      trials used a form of home care for acutely ill people, which included elements
      of crisis intervention. 45% of the crisis/home care group were unable to avoid
      hospital admission during their treatment period. Home care, however, may help
      avoid repeat admissions (n = 465, 3 randomised controlled trials, RR 0.72 CI 0.54
      to 0.92, NNT 11 CI 6 to 97), but these data are heterogeneous (I-squared 86%).
      Crisis/home care reduces the number of people leaving the study early (n = 594, 4
      randomised controlled trials, RR lost at 12 months 0.74 CI 0.56 to 0.98, NNT 13
      CI 7 to 130), reduces family burden (n = 120, 1 randomised controlled trial, RR
      0.34 CI 0.20 to 0.59, NNT 3 CI 2 to 4), and is a more satisfactory form of care
      for both patients and families. We found no differences in death or mental state
      outcomes. All studies found home care to be more cost effective than hospital
      care but all data were either skewed or unusable. No data on staff satisfaction,
      carer input, compliance with medication and number of relapses were available.
      REVIEWERS' CONCLUSIONS: Home care crisis treatment, coupled with an ongoing home
      care package, is a viable and acceptable way of treating people with serious
      mental illnesses. If this approach is to be widely implemented it would seem that
      more evaluative studies are needed.

PMID- 15495007
TI  - Fixed dose subcutaneous low molecular weight heparins versus adjusted dose
      unfractionated heparin for venous thromboembolism.
AB  - BACKGROUND: Low molecular weight heparins (LMWH) have been shown to be effective
      and safe in preventing venous thromboembolism (VTE), and may also be effective
      for the initial treatment of VTE. OBJECTIVES: To determine the effect of LMWH
      compared with unfractionated heparin (UFH) for the initial treatment of VTE.
      SEARCH STRATEGY: Trials were identified from the Cochrane Peripheral Vascular
      Diseases Group's Specialised Register, CENTRAL and LILACS. Colleagues and
      pharmaceutical companies were contacted for additional information. SELECTION
      CRITERIA: Randomised controlled trials comparing fixed dose subcutaneous LMWH
      with adjusted dose intravenous or subcutaneous UFH in people with VTE. DATA
      COLLECTION AND ANALYSIS: At least two reviewers assessed trials for inclusion and
      quality, and extracted data independently. MAIN RESULTS: Twenty-two studies were
      included (n = 8867). Thrombotic complications occurred in 151/4181 (3.6%)
      participants treated with LMWH, compared with 211/3941 (5.4%) participants
      treated with UFH (odds ratio (OR) 0.68; 95% confidence intervals (CI) 0.55 to
      0.84, 18 trials). Thrombus size was reduced in 53% of participants treated with
      LMWH and 45% treated with UFH (OR 0.69; 95% CI 0.59 to 0.81, 12 trials). Major
      haemorrhages occurred in 41/3500 (1.2%) participants treated with LMWH, compared
      with 73/3624 (2.0%) participants treated with UFH (OR 0.57; 95% CI 0.39 to 0.83,
      19 trials). In eighteen trials, 187/4193 (4.5%) participants treated with LMWH
      died, compared with 233/3861 (6.0%) participants treated with UFH (OR 0.76; 95%
      CI 0.62 to 0.92). Nine studies (n = 4451) examined proximal thrombosis; 2192
      participants treated with LMWH and 2259 with UFH. Subgroup analysis showed
      statistically significant reductions favouring LMWH in thrombotic complications
      and major haemorrhage. By the end of follow up, 80 (3.6%) participants treated
      with LMWH had thrombotic complications, compared with 143 (6.3%) treated with UFH
      (OR 0.57; 95% CI 0.44 to 0.75). Major haemorrhage occurred in 18 (1.0%)
      participants treated with LMWH, compared with 37 (2.1%) treated with UFH (OR
      0.50; 95% CI 0.29 to 0.85). Nine studies (n = 4157) showed a statistically
      significant reduction favouring LMWH with respect to mortality. By the end of
      follow up, 3.3% (70/2094) of participants treated with LMWH had died, compared
      with 5.3% (110/2063) of participants treated with UFH (OR 0.62; 95% CI 0.46 to
      0.84). REVIEWERS' CONCLUSIONS: LMWH is more effective than UFH for the initial
      treatment of VTE. LMWH significantly reduces the occurrence of major haemorrhage
      during initial treatment and overall mortality at follow up.

PMID- 15495008
TI  - Psychosocial and psychological interventions for preventing postpartum
      depression.
AB  - BACKGROUND: The cause of postpartum depression remains unclear, with extensive
      research suggesting a multi-factorial aetiology. However, epidemiological studies
      and meta-analyses of predictive studies have consistently demonstrated the
      importance of psychosocial and psychological variables. While interventions based
      on these variables may be effective treatment strategies, theoretically they may
      also be used in pregnancy and the early postpartum period to prevent postpartum
      depression. OBJECTIVES: Primary: to assess the effect of diverse psychosocial and
      psychological interventions compared with usual antepartum, intrapartum, or
      postpartum care to reduce the risk of developing postpartum depression.
      Secondary: to examine (1) the effectiveness of specific types of psychosocial and
      psychological interventions, (2) the effectiveness of individual versus group
      based interventions, (3) the effects of intervention onset and duration, and (4)
      whether interventions are more effective in women selected with specific risk
      factors. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group
      trials register (January 27 2004), the Cochrane Depression, Anxiety and Neurosis
      Group trials register (October 2003), the Cochrane Central Register of Controlled
      Trials (October 2003), MEDLINE (1966 to 2004), EMBASE (1980 to 2004) and CINAHL
      (1982 to 2004). We scanned secondary references and contacted experts in the
      field. SELECTION CRITERIA: All published and unpublished randomised controlled
      trials of acceptable quality comparing a psychosocial or psychological
      intervention with usual antenatal, intrapartum, or postpartum care. DATA
      COLLECTION AND ANALYSIS: Both reviewers participated in the evaluation of
      methodological quality and data extraction. Additional information was sought
      from several trial researchers. Results are presented using relative risk for
      categorical data and weighted mean difference for continuous data. MAIN RESULTS:
      Fifteen trials, involving over 7600 women, were included. Overall, women who
      received a psychosocial intervention were equally likely to develop postpartum
      depression as those receiving standard care (relative risk (RR) 0.81, 95%
      confidence interval (CI) 0.65 to 1.02). One promising intervention appears to be
      the provision of intensive postpartum support provided by public health nurses or
      midwives (RR 0.68, 95% CI 0.55 to 0.84). Identifying mothers 'at-risk' assisted
      the prevention of postpartum depression (RR 0.67, 95% CI 0.51 to 0.89).
      Interventions with only a postnatal component appeared to be more beneficial (RR
      0.76, 95% CI 0.58 to 0.98) than interventions that also incorporated an antenatal
      component. While individually-based interventions may be more effective (RR 0.76,
      95% CI 0.59 to 1.00) than those that are group-based, women who received multiple
      contact intervention were just as likely to experience postpartum depression as
      those who received a single-contact intervention. REVIEWERS' CONCLUSIONS: Overall
      psychosocial interventions do not reduce the numbers of women who develop
      postpartum depression. However, a promising intervention is the provision of
      intensive, professionally-based postpartum support.

PMID- 15495009
TI  - House dust mite control measures for asthma.
AB  - BACKGROUND: The major allergen in house dust comes from mites. Chemical, physical
      and combined methods of reducing mite allergen levels are intended to reduce
      asthma symptoms in people who are sensitive to house dust mites. OBJECTIVES: To
      assess the effects of reducing exposure to house dust mite antigens in the homes
      of people with mite-sensitive asthma. SEARCH STRATEGY: Cochrane Airways Group
      trials register, and PubMed and The Cochrane Library (last searches June 2004),
      reference lists. SELECTION CRITERIA: Randomised trials of mite control measures
      vs placebo or no treatment in asthmatic people known to be sensitive to house
      dust mites. DATA COLLECTION AND ANALYSIS: Two reviewers applied the trial
      inclusion criteria, assessed their quality and extracted the data independently.
      Study authors were contacted to clarify information. MAIN RESULTS: Forty-nine
      trials (2733 patients) were included; the number of patients has more than
      doubled since the last version of this review. Thirty-one trials assessed
      physical methods, ten assessed chemical methods, and eight a combination of
      chemical and physical methods. Despite the fact that many trials were of poor
      quality and would be expected to exaggerate the reported effect, we did not find
      an effect of the interventions. For the most frequently reported outcome, peak
      flow in the morning (1339 patients), the standardised mean difference was -0.02
      (95% confidence interval (CI) -0.13 to 0.08). There were no statistically
      significant differences either in number of patients improved (relative risk
      1.01, 95% CI 0.80 to 1.27), asthma symptom scores (standardised mean difference 
      0.01, 95% CI -0.10 to 0.13), or in medication usage (standardised mean difference
      -0.05, 95% CI -0.18 to 0.09). REVIEWERS' CONCLUSIONS: Chemical and physical
      methods aimed at reducing exposure to house dust mite allergens cannot be
      recommended. It is doubtful whether further studies, similar to the ones in our
      meta-analysis, are worthwhile. If other types of studies are considered, they
      should be methodologically rigorous and use other methods than those used so far,
      with careful monitoring of mite exposure and relevant clinical outcomes.

PMID- 15495010
TI  - Pharmacotherapy for social phobia.
AB  - BACKGROUND: Social phobia (SP), or social anxiety disorder, is a prevalent and
      disabling disorder. There is growing evidence that SP is mediated by specific
      neurobiological factors, and increased interest in the use of medication in its
      treatment. OBJECTIVES: To assess the effects of pharmacotherapy for Social
      Phobia, and to determine whether particular classes of medication are more
      effective and/or acceptable than others in its treatment. SEARCH STRATEGY:
      Studies of the pharmacotherapy of SP were identified using literature searches of
      the Cochrane Depression, Anxiety & Neurosis Group (CCDAN) specialised register,
      the Cochrane Central Register of Controlled Trials (The Cochrane Library issue 1,
      2004), MEDLINE (1966 to 2003) and PsycLit (1966 to 2003). In addition, published
      and unpublished RCTs were requested from SP researchers and pharmaceutical
      companies and additional studies of any language were sought in reference lists
      of retrieved articles. SELECTION CRITERIA: All RCTs of the pharmacotherapy of SP
      were considered for the review. DATA COLLECTION AND ANALYSIS: The quality of
      selected RCTs was independently assessed by 2 raters on the CCDAN Quality Rating
      Scale, with the same raters collating data on treatment response and SP symptom
      ratings. Investigators were contacted to obtain missing data. Summary statistics
      were stratified by medication class (SSRIs - selective serotonin reuptake
      inhibitors; MAOIs - Monoamine oxidase inhibitors; RIMAs - reversible inhibitors
      of monoamine oxidase A), from which dichotomous and continuous measures were
      calculated, heterogeneity was assessed, and subgroup/sensitivity analyses
      undertaken. MAIN RESULTS: 36 RCTs of a range of medications were included in the
      analysis (4268 participants), of which 26 were short-term (14 weeks or less). A
      funnel plot provided evidence of publication bias. Summary statistics for
      responder status (assessed using the Clinical Global Impressions scale change
      item (CGI-C)) from 25 short-term comparisons demonstrated superiority of various
      medication agents over placebo (relative risk of non-response (RR) = 0.63; 95% CI
      = 0.55, 0.72; random effects model). Response to treatment by serotonin reuptake
      inhibitors (N = 11; RR = 0.67; 95% CI = 0.59, 0.76), MAOIs (N = 3; RR = 0.43; 95%
      CI = 0.24, 0.76) and RIMAs (N = 6; RR = 0.74; 95% CI = 0.59, 0.91) supported the
      value of these agents. However, the SSRIs were significantly more effective than
      the RIMAs (Deeks' stratified test of heterogeneity (Deeks 2001): Qb = 29.82; p <
      0.00001). Summary statistics for SP symptoms from 16 comparisons using the
      Liebowitz Social Anxiety Scale (LSAS) showed a statistically significant
      difference between medication and placebo (weighed mean difference = -15.56,
      95%CI = -17.95, -13.16), with this effect once again most evident for the SSRIs.
      Medication was also significantly superior to placebo in reducing SP symptom
      clusters, comorbid depressive symptoms, and associated disability. The value of
      long-term medication treatment in treatment responders was supported by 3
      comparisons from maintenance studies (relative risk of non-response = 0.58; 95%
      CI = 0.39, 0.85) and 5 comparisons from relapse prevention studies (relative risk
      of relapse = 0.33; 95% CI = 0.22, 0.49). REVIEWERS' CONCLUSIONS: This review
      provides evidence that medication can be effective in treating SP over the short
      term, with the strongest evidence of treatment efficacy observed amongst the
      SSRIs. Furthermore, the data support continued pharmacotherapy in medication
      responders over the longer-term. Nevertheless, the possibility of publication has
      to be acknowledged. Additional issues for future research include the use of
      medication in children and adolescents with SP, and in SP with comorbid
      psychiatric disorders.

PMID- 15495011
TI  - Human albumin solution for resuscitation and volume expansion in critically ill
      patients.
AB  - BACKGROUND: Human albumin solutions are used in a range of medical and surgical
      problems. Licensed indications are the emergency treatment of shock and other
      conditions where restoration of blood volume is urgent, burns, and
      hypoproteinaemia. Human albumin solutions are more expensive than other colloids
      and crystalloids. OBJECTIVES: To quantify the effect on mortality of human
      albumin and plasma protein fraction (PPF) administration in the management of
      critically ill patients. SEARCH STRATEGY: We searched the Cochrane Injuries Group
      trials register, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE
      and BIDS Index to Scientific and Technical Proceedings. Reference lists of trials
      and review articles were checked, and authors of identified trials were
      contacted. The search was last updated in August 2004. SELECTION CRITERIA:
      Randomised controlled trials comparing albumin/PPF with no albumin/PPF, or with a
      crystalloid solution, in critically ill patients with hypovolaemia, burns or
      hypoalbuminaemia. DATA COLLECTION AND ANALYSIS: We collected data on the
      participants, albumin solution used, mortality at the end of follow up, and
      quality of allocation concealment. Analysis was stratified according to patient
      type. MAIN RESULTS: We found 32 trials meeting the inclusion criteria and
      reporting death as an outcome. There were 1632 deaths among 8452 trial
      participants. For hypovolaemia, the relative risk of death following albumin
      administration was 1.01 (95% confidence interval 0.92, 1.10). This estimate was
      heavily influenced by the results of the SAFE trial which contributed 91% of the
      information (based on the weights in the meta-analysis). For burns, the relative
      risk was 2.40 (1.11, 5.19) and for hypoalbuminaemia the relative risk was 1.38
      (0.94, 2.03). There was no substantial heterogeneity between the trials in the
      various categories (chi-square = 21.86, df = 25, p =0.64). The pooled relative
      risk of death with albumin administration was 1.04 (0.95, 1.13). REVIEWERS'
      CONCLUSIONS: For patients with hypovolaemia there is no evidence that albumin
      reduces mortality when compared with cheaper alternatives such as saline. There
      is no evidence that albumin reduces mortality in critically ill patients with
      burns and hypoalbuminaemia. The possibility that there may be highly selected
      populations of critically ill patients in which albumin may be indicated remains
      open to question. However, in view of the absence of evidence of a mortality
      benefit from albumin and the increased cost of albumin compared to alternatives
      such as saline, it would seem reasonable that albumin should only be used within
      the context of well concealed and adequately powered randomised controlled trial.

PMID- 15495012
TI  - Bed rest for acute low-back pain and sciatica.
AB  - BACKGROUND: Low-back pain (LBP) is a common reason for consulting a general
      practitioner, and advice on daily activities is an important part of the primary
      care management of low-back pain. OBJECTIVES: To assess the effects of advice to
      rest in bed for patients with acute LBP or sciatica. SEARCH STRATEGY: We searched
      the Cochrane Back Group Specialized Registry, CENTRAL, MEDLINE, EMBASE, Sport,
      and SCISEARCH to March 2003, reference lists of relevant articles, and contacted
      authors of relevant articles. SELECTION CRITERIA: Randomised or controlled
      clinical trials with quasi-randomisation (alternate allocation, case record
      numbers, dates of birth, etc.), in any language, where the effectiveness of
      advice to rest in bed was evaluated. The main outcomes of interest were pain,
      functional status, recovery and return to work. DATA COLLECTION AND ANALYSIS: Two
      reviewers independently selected trials for inclusion, assessed the internal
      validity of included trials and extracted data. Investigators were contacted to
      obtain missing information. MAIN RESULTS: Eleven trials (1963 patients) were
      included in this updated version. There is high quality evidence that people with
      acute LBP who are advised to rest in bed have a little more pain [Standardised
      Mean Difference (SMD) 0.22 (95% Confidence Interval (CI): 0.02, 0.41)] and a
      little less functional recovery [SMD 0.29 (95% CI: 0.05, 0.45)] than those
      advised to stay active. For patients with sciatica, there is moderate quality
      evidence of little or no difference in pain [SMD -0.03 (95% CI: -0.24, 0.18)] or
      functional status [SMD 0.19 (95% CI: -0.02, 0.41)] between bed rest and staying
      active. For patients with acute LBP, there is moderate quality evidence of little
      or no difference in pain intensity or functional status between bed rest and
      exercises. For patients with sciatica, there is moderate quality evidence of
      little or no difference in pain intensity between bed rest and physiotherapy, but
      small improvements in functional status [Weighted Mean Difference 6.9 (on a 0-100
      scale) (95% CI: 1.09, 12.74)] with physiotherapy. There is moderate quality
      evidence of little or no difference in pain intensity or functional status
      between two to three days and seven days of bed rest. REVIEWERS' CONCLUSIONS: For
      people with acute LBP, advice to rest in bed is less effective than advice to
      stay active. For patients with sciatica, there is little or no difference between
      advice to rest in bed and advice to stay active. There is little or no difference
      in the effect of bed rest compared to exercises or physiotherapy, or seven days
      of bed rest compared with two to three.

PMID- 15495013
TI  - Venepuncture versus heel lance for blood sampling in term neonates.
AB  - BACKGROUND: Heel lance has been the conventional method of blood sampling in
      neonates for screening tests. Neonates undergoing this procedure experience pain.
      Despite various studies evaluating the role of pharmacological and non
      pharmacological interventions to date, there are no effective and practical
      methods to alleviate pain from heel lance. OBJECTIVES: To determine whether
      venepuncture or heel lance is less painful and more effective for blood sampling
      in term neonates. SEARCH STRATEGY: Systematic search in accordance with the
      Cochrane Neonatal Collaborative Review Group. All randomized controlled trials
      which compared pain response to venepuncture vs. heel lance were identified using
      MEDLINE (1966-June 2004), EMBASE (1980-June 2004), CINAHL (1982-June 2004,
      Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library,
      Issue 2, 2004), reference lists of identified trials and personal files. No
      language restrictions were applied. SELECTION CRITERIA: Randomized controlled
      trials which compared pain response to venepuncture vs. heel lance were selected
      for this review. DATA COLLECTION AND ANALYSIS: Data regarding the primary outcome
      of pain response to venepuncture vs. heel lance as assessed by validated pain
      measures were abstracted. Secondary outcomes including the need of repeat blood
      sampling, bruising/hematoma at local site, and parental perception of their own
      anxiety and infant's pain were abstracted. All data were analysed using RevMan
      4.2. When possible, meta-analysis was done using relative risk (RR) and risk
      difference (RD), along with their 95% confidence intervals (CI). If RD was
      significant, number needed to treat (NNT) was calculated. Weighted mean
      difference (WMD) was used for continuous data. When present, statistically
      significant between study heterogeneity was reported including the I(2) test.
      MAIN RESULTS: Four trials were eligible for inclusion in the review. Pain
      assessments were made using validated pain measures including Neonatal Infant
      Pain Scale (NIPS), Neonatal Facial Action Coding System (NFCS), Premature Infant
      Pain Profile (PIPP) score and cry characteristics. Two trials did not report on
      outcomes for all enrolled infants (not intention to treat analyses). Despite the
      heterogeneity in the pain measures used, all studies showed statistically
      significantly lower pain scores for venepuncture as compared to heel lance. A
      meta-analysis of the NIPS scores during the first minute of the procedure
      (reported in two studies) was statistically significantly decreased in the VP
      group compared to the HL group [WMD -1.84 (95% CI -2.61, -1.06)]. There was no
      statistically significant heterogeneity for this outcome (p = 0.22; I(2) 33.3%).
      The RR for requiring more than one skin puncture for venepuncture vs. heel lance
      (reported in 3 studies) was 0.30 (95% CI 0.18, 0.49. The risk difference was -39%
      (95% CI -50%, -28%). For this outcome there was statistically significant between
      study heterogeneity (for RR, p=0.02, I(2 )74.3%; for RD, p=0.0001, I(2) 88.9%).
      The number needed to treat (NNT) to avoid one repeat skin puncture was 3 (95% CI
      2, 4). In one study, maternal anxiety was noted to be higher in the venepuncture
      group as compared to heel lance group prior to the procedure; however, after
      observing the procedure, mothers rated their infant's pain to be lower in the
      venepuncture group. REVIEWERS' CONCLUSIONS: Venepuncture, when performed by a
      skilled phlebotomist, appears to be the method of choice for blood sampling in
      term neonates. For each three venepunctures instead of heel lance, the need for
      one additional skin puncture can be avoided. Further well designed randomized
      controlled trials need to be conducted. The interventions should be compared in
      settings where several individuals perform the venepuncture and/or the heel
      lance.

PMID- 15495014
TI  - Laparoscopic versus open surgery for suspected appendicitis.
AB  - BACKGROUND: Laparoscopic surgery for acute appendicitis has been proposed to have
      advantages over conventional surgery. OBJECTIVES: To compare the diagnostic and
      therapeutic effects of laparoscopic and conventional 'open' surgery. SEARCH
      STRATEGY: We searched the Cochrane Central Register of Controlled Trials,
      MEDLINE, EMBASE, SciSearch, the congress proceedings of endoscopic surgical
      societies. SELECTION CRITERIA: We included randomized clinical trials comparing
      laparoscopic (LA) versus open appendectomy (OA) in adults or children. Studies
      comparing immediate OA versus diagnostic laparoscopy (followed by LA or OA if
      necessary) were separately identified. DATA COLLECTION AND ANALYSIS: Two
      reviewers independently assessed trial quality. Missing information or data was
      requested from the authors. We used odds ratios (OR), relative risks (RR), and
      95% confidence intervals (CI) for analysis. MAIN RESULTS: We included 54 studies,
      of which 45 compared LA (with or without diagnostic laparoscopy) vs. OA in
      adults. Wound infections were less likely after LA than after OA (OR 0.45; CI
      0.35 to 0.58), but the incidence of intraabdominal abscesses was increased (OR
      2.48; CI 1.45 to 4.21). The duration of surgery was 12 minutes (CI 7 to 16)
      longer for LA. Pain on day 1 after surgery was reduced after LA by 9 mm (CI 5 to
      13 mm) on a 100 mm visual analogue scale. Hospital stay was shortened by 1.1 day
      (CI 0.6 to 1.5). Return to normal activity, work, and sport occurred earlier
      after LA than after OA. While the operation costs of LA were significantly
      higher, the costs outside hospital were reduced. Five studies on children were
      included, but the result do not seem to be much different when compared to
      adults. Diagnostic laparoscopy reduced the risk of a negative appendectomy, but
      this effect was stronger in fertile women (RR 0.20; CI 0.11 to 0.34) as compared
      to unselected adults (RR 0.37; CI 0.13 to 1.01). REVIEWERS' CONCLUSIONS: In those
      clinical settings where surgical expertise and equipment are available and
      affordable, diagnostic laparoscopy and LA (either in combination or separately)
      seem to have various advantages over OA. Some of the clinical effects of LA,
      however, are small and of limited clinical relevance. In spite of the mediocre
      quality of the available research data, we would generally recommend to use
      laparoscopy and LA in patients with suspected appendicitis unless laparoscopy
      itself is contraindicated or not feasible. Especially young female, obese, and
      employed patients seem to benefit from LA.

PMID- 15495015
TI  - Mobilisation strategies after hip fracture surgery in adults.
AB  - BACKGROUND: Hip fracture, which happens in predominantly elderly populations,
      often results in a reduction in mobility. Care programmes after hip fracture
      surgery include strategies for mobilisation, such as early weight bearing and
      gait retraining. Other mobilisation strategies, such as exercises and physical
      training, are used at various stages in rehabilitation including after discharge
      from hospital. OBJECTIVES: To evaluate the effects of different mobilisation
      strategies and programmes after hip fracture surgery. SEARCH STRATEGY: We
      searched the Cochrane Musculoskeletal Injuries Group Specialised Register (May
      2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library
      Issue 2, 2004), MEDLINE and other databases, conference proceedings and reference
      lists of articles. SELECTION CRITERIA: All randomised or quasi-randomised trials
      comparing different mobilisation strategies/programmes after hip fracture
      surgery. DATA COLLECTION AND ANALYSIS: The reviewers independently assessed trial
      quality and extracted data. MAIN RESULTS: Our third update, which extended the
      review scope to cover the whole rehabilitation period, included four new trials.
      Most of the 10 included trials were small and all had methodological limitations,
      including inadequate follow up. Seven trials evaluated mobilisation strategies
      started soon after hip fracture surgery. One trial (273 participants) found no
      statistically significant differences in unfavourable outcomes for weight bearing
      started at two versus 12 weeks after internal fixation of a displaced
      intracapsular fracture. Of two trials (188 participants) comparing a more with a
      less intensive regimen of physiotherapy, one reported a lack of demonstrable
      difference in recovery of the two patient groups, and the other found a higher
      level of drop-out in the more intensive group with no difference in length of
      hospital stay. One trial (80 participants) comparing two-week programmes of
      weight-bearing versus non-weight-bearing exercise found some short-term
      improvement in mobility and balance in the weight-bearing exercise group. One
      trial (80 participants) found improved mobility, leg extension power and Barthel
      score in those given a quadriceps muscle strengthening exercise programme. One
      trial (40 participants) found no statistically significant difference in recovery
      of mobility and time to hospital discharge after a treadmill versus conventional
      gait retraining programme. One trial (27 participants) comparing neuromuscular
      stimulation of the quadriceps muscle with placebo found a greater recovery of pre
      fracture mobility in the stimulation group. The interventions tested by the three
      remaining trials started after hospital discharge. One trial (28 participants)
      found improved outcome after 12 weeks of intensive physical training. One trial
      (120 participants) found improved outcome after home-based exercises started
      around 22 weeks from injury. One trial (44 participants) found home-based weight
      bearing exercises starting at seven months produced no statistically significant
      differences aside, perhaps, for greater quadriceps strength. REVIEWERS'
      CONCLUSIONS: There is insufficient evidence from randomised trials to determine
      the effectiveness of the various mobilisation strategies examined in this review
      that start either in the early post-operative period or during the later
      rehabilitation period. Further research is required to establish the possible
      benefits of the additional provision of interventions primarily aimed at
      enhancing mobility.

PMID- 15495016
TI  - Depot pipotiazine palmitate and undecylenate for schizophrenia.
AB  - BACKGROUND: Antipsychotic drugs are usually given orally but compliance may be
      problematic. The development of depot injections in the 1960s gave rise to their
      extensive use as a means of long-term maintenance treatment. Pipotiazine
      palmitate is a depot from the phenothiazine family of antipsychotic drugs.
      OBJECTIVES: To assess the clinical, social and economic effects of depot
      pipotiazine palmitate and undecylenate compared with placebo, oral antipsychotics
      and other depot antipsychotic preparations for people with schizophrenia. SEARCH
      STRATEGY: For this update we searched the Cochrane Schizophrenia Group's Register
      (June 2003). We also inspected references of all identified trials for more
      studies and contacted relevant industries. SELECTION CRITERIA: We included all
      randomised clinical trials comparing depot pipotiazine palmitate and undecylenate
      to oral antipsychotics or other depot preparations for people with schizophrenia.
      DATA COLLECTION AND ANALYSIS: We reliably selected, quality rated and
      independently extracted data from relevant studies. We calculated the random
      effects relative risk (RR), the 95% confidence intervals (CI) and, where possible
      the number needed to treat (NNT) on an intention-to-treat basis. For continuous
      data, we calculated weighted mean differences (WMD). We only presented scale data
      for those tools that had attained pre-specified levels of quality. MAIN RESULTS:
      When pipotiazine palmitate was compared with 'standard' oral antipsychotic no
      differences were found for outcomes of global impression (n=53, 1 RCT, RR 2.57,
      CI 0.8 to 8.6), relapse (n=124, 1 RCT, RR 1.55 CI 0.76 to 3.2), study attrition
      (n=219, 3 RCTs, RR 1.37 CI 0.8 to 2.4) and behaviour (n=124, 1 RCT, WMD 4.65, CI 
      1.1 to 10.4). There was also no reported difference in adverse effects such as
      tardive dyskinesia or the need for anticholinergic drugs. Sixteen studies
      compared pipotiazine palmitate with other depot preparations (n=1123).
      Pipotiazine palmitate was consistently equivalent to other depots in terms of a
      range of outcomes, including global impression (n=217, 4 RCTs, RR not improved
      0.99 CI 0.91 to 1.07), relapse (n=239, 5 RCTs, RR relapse by 1 year 0.98 CI 0.55
      to 1.75), and adverse effects (n=337, 5 RCTs, RR needing anticholinergic
      medication 0.98 CI 0.84 to 1.15). REVIEWERS' CONCLUSIONS: Although well-conducted
      and reported randomised trials are still needed to fully inform practice (no
      trial data exists reporting hospital and services outcomes, satisfaction with
      care and economics) pipotiazine palmitate is a viable choice for both clinician
      and recipient of care.

PMID- 15495017
TI  - Galantamine for Alzheimer's disease.
AB  - BACKGROUND: Galantamine is a specific, competitive, and reversible
      acetylcholinesterase inhibitor. OBJECTIVES: To assess the clinical effects of
      galantamine in patients with probable or possible Alzheimer's disease (AD), and
      potential moderators of effect. SEARCH STRATEGY: The trials were identified from
      a search of the Specialized Register of the Cochrane Dementia and Cognitive
      Improvement Group, last updated on 25 August 2005 using the terms galanthamin*,
      galantamin* and Reminyl. Published reviews were inspected for further sources.
      Additional information was collected from unpublished clinical research reports
      for galantamine obtained from Janssen. SELECTION CRITERIA: Trials selected were
      randomised, double-blind, parallel-group comparisons of galantamine with placebo
      for a treatment duration of greater than 4 weeks in subjects with AD. DATA
      COLLECTION AND ANALYSIS: Data were extracted independently by the reviewers and
      pooled where appropriate and possible. Outcomes of interest include the clinical
      global impression of change (CIBIC-plus or CGIC), Alzheimer's Disease Assessment
      Scale-cognitive sub scale (ADAS-cog), Alzheimer's Disease Cooperative
      Study/Activities of Daily Living (ADCS-ADL), Disability Assessment for Dementia
      scale (DAD) and Neuropsychiatric Inventory (NPI). Potential moderating variables
      of treatment effect assessed included trial duration, dose, and diagnosis of
      possible vs. probable Alzheimer's disease. MAIN RESULTS: Seven trials with a
      total 3777 subjects were included in the analysis. Treatment with galantamine led
      to a significantly greater proportion of subjects with improved or unchanged
      global rating scale rating (k=7), at all dosing levels except for 8mg/d .
      Confidence intervals for the ORs overlapped across the dose range of 16mg to 36mg
      per day, with point estimates of 1.6-2.1 when analysed with the intention-to
      treat sample. Treatment with galantamine also led to significantly greater
      reduction in ADAS-cog score at all dosing levels (k=7), with greater effect over
      6 months compared to 3 months. Confidence intervals again overlapped. Point
      estimate of effect was lower for 8mg/d but similar for 16mg to 36mg per day. For
      example, treatment effect for 24mg/d over 6 months was 3.1point reduction in ADAS
      cog (95%CI 2.6-3.7, k=4, ITT).ADCS-ADL, DAD and NPI were reported only in a small
      proportion of trials: all showed significant treatment effect in some individual
      trials at least. Confidence interval of treatment effect for the one trial
      recruiting patients with possible AD overlapped with the other six recruiting
      patients with probable AD. Galantamine's adverse effects appeared similar to
      those of other cholinesterase inhibitors and to be dose related. REVIEWERS'
      CONCLUSIONS: Subjects in these trials were similar to those seen in earlier anti
      dementia AD trials, consisting primarily of mildly to moderately impaired
      outpatients. Galantamine's effect on more severely impaired subjects has not yet
      been assessed.Nevertheless, this review shows consistent positive effects for
      galantamine for trials of 3 to 6 months duration. Although there was not a
      statistically significant dose-response effect, doses above 8mg/d were, for the
      most part, consistently statistically significant. Galantamine's safety profile
      is similar to that of other cholinesterase inhibitors with respect to
      cholinergically mediated gastrointestinal symptoms. It appears that doses of 16
      mg/d were best tolerated in the single trial where medication was titrated over a
      4 week period, and because this dose showed statistically indistinguishable
      efficacy with higher doses, it is probably most preferable initially. Longer term
      use of galantamine has not been assessed in a controlled fashion.

PMID- 15495018
TI  - Immediate postabortal insertion of intrauterine devices.
AB  - BACKGROUND: Insertion of an intrauterine device (IUD) immediately after an
      abortion has several potential advantages. The woman is known not to be pregnant,
      a major concern for clinicians. For example, many clinicians refuse to insert an
      IUD in a woman who is not menstruating. After induced abortion, a woman's
      motivation to use contraception may be high. However, insertion of an IUD
      immediately after a pregnancy ends carries potential risks as well. For example,
      the risk of spontaneous expulsion may be increased due to recent cervical
      dilation. OBJECTIVES: To assess the safety and efficacy of IUD insertion
      immediately after spontaneous or induced abortion. SEARCH STRATEGY: We used
      MEDLINE, Popline, and EMBASE computer searches, supplemented by review articles
      and contacts with investigators. SELECTION CRITERIA: We sought all randomized
      controlled trials that had at least one treatment arm that involved IUD insertion
      immediately after an induced abortion or after curettage for spontaneous
      abortion. We identified 12 trials which described random assignment but excluded
      three from this review. Two of these revealed unethical research conduct, and one
      used alternate assignment to treatments. DATA COLLECTION AND ANALYSIS: We
      evaluated the methodological quality of each report and abstracted information
      onto a data collection form. We focused on gross discontinuation rates (single
      decrement life table analysis) for accidental pregnancy, perforation, expulsion,
      and pelvic inflammatory disease. We entered the data into RevMan 3.1 for analysis
      of Peto odds ratios. MAIN RESULTS: In large multicenter trials, the TCu 220C
      device proved superior to either the Lippes Loop D or the Copper 7 IUDs for
      immediate postabortal insertion. In single-center trials, the Nova T IUD had a
      significantly higher discontinuation rate for pregnancy than did the Multiload
      250 (OR 4.5; 95% CI 1.0-19.8), while the Nova T had a significantly lower
      discontinuation rate for pregnancy than did the TCu 200 (OR 0.3; 95% CI 0.1-0.9).
      The levonorgestrel-releasing device was more effective in preventing pregnancy
      than was the Nova T. Only one trial compared immediate vs. delayed insertion. In
      this trial, the performance of the Copper 7 IUD inserted immediately after
      abortion was inferior to that after interval insertion (remote from pregnancy),
      although the differences were not statistically significant. REVIEWERS'
      CONCLUSIONS: Insertion of an IUD immediately after abortion is both safe and
      practical. IUD expulsion rates appear higher than after interval insertions.

PMID- 15495019
TI  - Over-the-counter medications for acute cough in children and adults in ambulatory
      settings.
AB  - BACKGROUND: Acute cough due to upper respiratory tract infection (URTI) is a
      common symptom. Many health practitioners recommend non-prescription over-the
      counter (OTC) medicines as a first-line treatment for cough, but there is little
      evidence as to whether these drugs are effective. OBJECTIVES: To assess the
      effects of oral over-the-counter cough preparations for acute cough. SEARCH
      STRATEGY: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library Issue 2, 2004); MEDLINE (January 1966 to June
      Week 3, 2004); EMBASE (January 1990 to March 2004); and the UK Department of
      Health National Research Register (December 2003, http://www.update
      software.com/National/nrr-frame.html). We also searched personal collections of
      references and reference lists of articles. We wrote to study investigators and
      pharmaceutical companies for information on further published or unpublished
      studies. There were no constraints based on language or publication status.
      SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing oral OTC cough
      preparations with placebo in children and adults suffering from acute cough in
      ambulatory settings. We considered all cough outcomes (such as frequency and
      severity, continuous and categorical data, using different ways of measurement).
      The second outcomes of interest were adverse effects. DATA COLLECTION AND
      ANALYSIS: Two investigators screened potentially relevant citations
      independently. Any differences at any stage of the review were resolved by
      discussion. We also extracted data and assessed the quality of studies
      independently. We contacted investigators for additional information and
      performed quantitative analysis when appropriate data were available. MAIN
      RESULTS: Twenty four trials (17 in adults, seven in children) involving 3,392
      people (2,876 adults and 516 children) were included. RESULTS OF STUDIES IN
      ADULTS: 1. Antitussives: Six trials compared antitussives with placebo. Codeine
      was no more effective than placebo in reducing cough symptoms. Two studies
      favoured dextromethorphan over placebo, whereas a third did not show an effect.
      Moguisteine was no more effective than placebo apart from a reduction of cough in
      a subgroup of participants with more severe night cough. 2. Expectorants: Two
      trials compared guaifenesin with placebo. In the larger study, 75 per cent of
      participants taking guaifenesin stated that the medicine was helpful compared to
      31 per cent in the control group. In the second study, both groups showed
      improvement with respect to cough frequency and severity, with no statistically
      significant differences between groups. 3. Mucolytics: One trial compared a
      mucolytic with placebo. Active treatment reduced cough frequency and symptom
      scores on day four and eight. 4. Antihistamine-decongestant combinations: Two
      studies compared antihistamine-decongestant combinations with placebo.
      Antihistamine-decongestants were significantly more effective than placebo in one
      of the studies, whereas the other did not show any difference between the study
      groups. 5. Other drug combinations: Three studies compared combinations of drugs
      other than antihistamine-decongestant with placebo. Two studies were effective in
      reducing cough symptoms, and one study showed relief at night but not during the
      day. 6. Antihistamines: Three trials compared antihistamines with placebo.
      Antihistamines were no more effective than placebo in relieving cough symptoms.
      RESULTS OF STUDIES IN CHILDREN: 1. Antitussives: Antitussives were no more
      effective than placebo (one study) 2. Expectorants: No studies using expectorants
      met our inclusion criteria. 3. Mucolytics: The results of one trial favoured
      active treatment over placebo from day four until day 10. 4. Antihistamine
      decongestant combinations: Two studies showed no difference between antihistamine
      decongestant combinations and placebo. 5. Other drug combinations: One trial
      tested two paediatric cough syrups. Compared to placebo, both preparations showed
      a 'satisfactory response' in 46 per cent and 56 per cent of children compared to
      21 per cent of children in the placebo group. One study compared an
      antitussive/bronchodilator combination in children, which showed no difference
      between the treatment groups. 6. Antihistamines: In one trial that tested
      antihistamines active treatment was no more effective than placebo. REVIEWERS'
      CONCLUSIONS: There is no good evidence for or against the effectiveness of OTC
      medicines in acute cough. The results of this review have to be interpreted with
      caution due to differences in study designs, populations, interventions and
      outcomes between studies. The numbers of studies in each group were small, and
      studies often showed conflicting results. Effect sizes in many studies were
      unclear and it is questionable as to whether all of the positive results are
      clinically relevant. More evidence about the effectiveness of OTC cough
      preparations would be helpful, as identification of effective self-care
      treatments may help reduce the burden of days lost at work due to acute cough as
      well as the number of consultations in primary care. Identification of
      ineffective preparations could avoid costs for consumers and health care
      providers.

PMID- 15495020
TI  - Physical methods for preventing deep vein thrombosis in stroke.
AB  - BACKGROUND: Deep vein thrombosis (DVT) and resulting pulmonary embolism (PE) are
      uncommon but important complications of stroke. There is good evidence that
      anticoagulants can reduce the risk of DVT and PE after stroke, but this benefit
      is offset by a small but definite risk of serious haemorrhages. Physical methods
      to prevent DVT and PE (such as compression stockings applied to the legs) are not
      associated with any bleeding risk and are effective in some categories of medical
      and surgical patients. We sought to assess their effects in stroke patients.
      OBJECTIVES: To assess the effectiveness and safety of physical methods of
      preventing the onset of deep vein thrombosis and fatal or non fatal pulmonary
      embolism in patients with recent stroke. SEARCH STRATEGY: We searched the
      Cochrane Stroke Group trials register (last searched June 2003). In addition we
      searched the following electronic bibliographic databases: Cochrane Central
      Register of Controlled Trials (The Cochrane Library, Issue 2, 2003), MEDLINE
      (1966 to June 2003), EMBASE (1980 to June 2003) and CINAHL (1982 to June 2003).
      The reference lists of all relevant papers were screened for additional trials.
      SELECTION CRITERIA: Unconfounded randomised controlled trials comparing physical
      methods for the prevention of DVT with control, in which prophylaxis was started
      within seven days of the onset of stroke. DATA COLLECTION AND ANALYSIS: Two
      reviewers independently searched for relevant trials and three others
      independently checked the results. MAIN RESULTS: We identified two small trials
      which included 123 patients. In one trial of 97 patients, compression stockings
      were associated with a non significant trend towards a reduction in DVT detected
      by Doppler ultrasound. In one trial of 26 patients, an intermittent pneumatic
      compression device was not associated with a significant reduction in DVT
      detected by 125-I-fibrinogen scanning. Overall, physical methods were not
      associated with a significant reduction in DVT during the treatment period in
      survivors (Odds ratio (OR) 0.54, 95% Confidence Interval (CI) 0.18 to 1.57) or
      death (OR 1.54, 95% CI 0.5 to 4.77). REVIEWERS' CONCLUSIONS: There is
      insufficient evidence from randomised trials to support the routine use of
      physical methods for preventing DVT in acute stroke.

PMID- 15495021
TI  - Corticosteroids for Bell's palsy (idiopathic facial paralysis).
AB  - BACKGROUND: Inflammation and oedema of the facial nerve are implicated in causing
      Bell's palsy. Corticosteroids have a potent anti-inflammatory action which should
      minimise nerve damage and thereby improve the outcome of patients suffering from
      this condition. OBJECTIVES: The objective of this review was to assess the effect
      of steroid therapy in the recovery of patients with Bell's palsy. SEARCH
      STRATEGY: We searched the Cochrane Neuromuscular Disease Group register (searched
      December 2003) for randomised trials, as well as MEDLINE (January 1966 to April
      2003), EMBASE (January 1980 to April 2003) and LILACS (January 1982 to April
      2003). We contacted known experts in the field to identify additional published
      or unpublished trials. SELECTION CRITERIA: Randomised trials comparing different
      routes of administration and dosage schemes of corticosteroid or
      adrenocorticotrophic hormone therapy versus a control group where no therapy
      considered effective for this condition was administered, unless it was also
      given in a similar way to the experimental group. DATA COLLECTION AND ANALYSIS:
      Two reviewers independently assessed eligibility, trial quality, and extracted
      the data. MAIN RESULTS: Four trials with a total of 179 patients were included.
      One trial compared cortisone acetate with placebo; one compared prednisone plus
      vitamins, with vitamins alone; one compared high-dose prednisone administered
      intravenously against saline solution, and one, not-placebo controlled, tested
      the efficacy of methylprednisolone. Allocation concealment was appropriate in two
      trials, and the data reported allowed an intention-to-treat analysis. The data
      included in the meta-analyses were collected from three trials with a total of
      117 patients. Overall 13/59 (22%) of the patients allocated to steroid therapy
      had incomplete recovery of facial motor function six months after randomisation,
      compared with 15/58 (26%) in the control group. This reduction was not
      significant (relative risk 0.86, 95% confidence interval 0.47 to 1.59). The
      reduction in the proportion of patients with cosmetically disabling sequelae six
      months after randomisation was also not significant (relative risk 0.86, 95%
      confidence interval 0.38 to 1.98). The trial not included in the meta-analysis
      showed a non-significant difference in outcomes between the arms. REVIEWERS'
      CONCLUSIONS: The available evidence from randomised controlled trials does not
      show significant benefit from treating Bell's palsy with corticosteroids. More
      randomised controlled trials with a greater number of patients are needed to
      determine reliably whether there is real benefit (or harm) from the use of
      corticosteroid therapy in patients with Bell's palsy.

PMID- 15495022
TI  - Central action beta-blockers versus placebo for neuroleptic-induced acute
      akathisia.
AB  - BACKGROUND: Neuroleptic-induced akathisia is a common, distressing early-onset
      adverse effect of neuroleptic drugs. It has been associated with poor treatment
      compliance and an increased risk of relapse. OBJECTIVES: To determine the effects
      of central action beta-blockers compared with placebo for people with neuroleptic
      induced acute akathisia. SEARCH STRATEGY: We updated previous searches of the
      Cochrane Schizophrenia Group Register (May 1999), Biological Abstracts (January
      1982-March 1999), The Cochrane Library (issue 3 1999), EMBASE (January 1980-March
      1999), LILACS (January 1982-March 1999), MEDLINE (January 1964-March 1999),
      PsycLIT (January 1974-March 1999), and SCISEARCH by searching the Cochrane
      Schizophrenia Group Register (November 2003). We sought further references from
      published trials and their authors. SELECTION CRITERIA: We included all
      randomised controlled clinical trials of central action beta-blockers versus
      placebo for people with neuroleptic-induced acute akathisia. 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 we calculated
      Weighted Mean Differences (WMD). MAIN RESULTS: We identified three randomised
      controlled trials (total n=51, maximum duration 72 hours). We were not able to
      draw any firm conclusions from such a small data set. In the two 48 hour studies
      no-one experienced full remission of akathisia, and only one person in each group
      experienced a 50% remission (n=11, 1 RCT, RR 1.04 CI 0.59 -1.83). One trial
      stated that no adverse effects occurred in the two groups (n=20, 1 RCT, RR not
      estimable). The 72 hour study did not show any statistical difference between the
      central acting beta-blocker (ICI 118,551) and placebo for the outcome 'no
      change/worse' (n=10, RR 0.22 CI 0.0 to 1.5). REVIEWERS' CONCLUSIONS: There are
      insufficient data to recommend beta-blocking drugs for akathisia. These drugs are
      experimental for this problem, and this review highlights the need for more
      evaluative studies.

PMID- 15495023
TI  - Pharmacological interventions for non-ulcer dyspepsia.
AB  - BACKGROUND: The commonest cause of upper gastrointestinal symptoms is non-ulcer
      dyspepsia (NUD) and yet the pathophysiology of this condition has been poorly
      characterised and the optimum treatment is uncertain. It is estimated that 450
      million pounds is spent on dyspepsia drugs in the UK each year. OBJECTIVES: This
      review aims to determine the effectiveness of six classes of drugs (antacids,
      histamine H2 antagonists, proton pump inhibitors, prokinetics, mucosal protecting
      agents and antimuscarinics) in the improvement of either the individual or global
      dyspepsia symptom scores and also quality of life scores patients with non-ulcer
      dyspepsia. SEARCH STRATEGY: Trials were located through electronic searches of
      the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL and
      SIGLE, using appropriate subject headings and text words, searching
      bibliographies of retrieved articles, and through contacts with experts in the
      fields of dyspepsia and pharmaceutical companies. SELECTION CRITERIA: All
      randomised controlled trials (RCTs) comparing drugs of any of the six groups with
      each other or with placebo for non-ulcer dyspepsia (NUD). DATA COLLECTION AND
      ANALYSIS: Data were collected on dyspeptic symptom scores either individual or
      global symptom assessments and also quality of life scores and adverse effects.
      MAIN RESULTS: A total of 11796 citations were obtained. 157 trials were retrieved
      and 98 trials fulfilled our eligibility criteria. However, subsequent data
      extraction was not possible in 31 trials. The final 67 trials were included in
      the meta-analysis. Prokinetics (14 trials with dichotomous outcomes generating
      1053 patients; relative risk reduction [RRR] = 48%; 95% confidence intervals [CI]
      = 27% to 63%), H2RAs (11 trials generating 2,164 patients; RRR = 22%; 95% CI = 7%
      to 35%) and PPIs (8 trials generating 3,293 patients; RRR = 14%; 95% CI = 5% to
      22%) were significantly more effective than placebo. Bismuth salts (6 trials
      generating 311 patients; RRR = 40%; 95% CI = -3 to 65%) were superior to placebo
      but this was of marginal statistical significance. Antacids (one trial generating
      109 patients; RRR = -2%; 95% CI = -36% to 24%) and sucralfate (two trials
      generating 246 patients; RRR = 29%; 95% CI = -40% to 64%) were not statistically
      significantly superior to placebo. A funnel plot suggested that the prokinetic
      and H2RA results could be due to publication bias. REVIEWERS' CONCLUSIONS: There
      is evidence that anti-secretory therapy may be effective in NUD. The trials
      evaluating prokinetic therapy are difficult to interpret as the meta-analysis
      result could have been due to publication bias. The effect of these drugs is
      likely to be small and many patients will need to take them on a long-term basis
      so economic analyses would be helpful and ideally the therapies assessed need to
      be inexpensive and well tolerated.

PMID- 15495024
TI  - Extended versus limited lymph nodes dissection technique for adenocarcinoma of
      the stomach.
AB  - BACKGROUND: Surgeons disagree about the merits and risks of radical lymph node
      clearance during gastrectomy for cancer. OBJECTIVES: To evaluate survival and
      peri-operative mortality after limited or extended lymph node removal during
      gastrectomy for cancer. SEARCH STRATEGY: We searched MEDLINE, EMBASE, CancerLit,
      LILACS, Central Medical Journal Japanese Database and the Cochrane register,
      references from relevant articles and conference proceedings. We contacted known
      workers in the field. SELECTION CRITERIA: Studies published after 1970 which
      reported 5 year survival or postoperative mortality rates, and clearly defined
      the node dissection performed, were considered. We excluded studies which overtly
      included patients receiving perioperative chemotherapy, and comparisons with
      clear systematic treatment allocation bias. Randomised controlled trials (RCTs),
      non-randomised comparisons and observational studies were considered separately.
      DATA COLLECTION AND ANALYSIS: Three reviewers selected trials for inclusion.
      Quality assessment and data extraction were performed independently by two
      reviewers. Results of trials of similar design were pooled. Meta-analysis was
      performed separately for randomised and non-randomised comparisons. MAIN RESULTS:
      Two randomised and two non-randomised comparisons of limited (D1) versus extended
      (D2) node dissection and 11 cohort studies of either D1 or D2 resection were
      analysed. Meta-analysis of randomised trials did not reveal any survival benefit
      for extended lymph node dissection (Risk ratio = 0.95 (95% CI 0.83 - 1.09), but
      showed increased postoperative mortality (RR 2.23, 95% CI 1.45 - 3.45). Pre
      specified subgroup analysis suggested a possible benefit in stage T3+ tumours (RR
      = 0.68, 95% CI 0.42-1.10). Non-randomised comparisons showed no significant
      survival benefit for extended dissection (RR 0.92, 95% CI 0.83 -1.02), but
      decreased mortality (RR 0.65, 95% CI 0.45-0.93). Subgroup analysis showed
      apparent benefit in UICC stage II and IIIa. Observational studies of D2 resection
      reported much better mortality and survival than those of D1 surgery, but the
      settings were strikingly different. REVIEWERS' CONCLUSIONS: D2 dissection carries
      increased mortality risks associated with spleen and pancreas resection, and
      probably with inexperience and low case volumes. Randomised studies show no
      evidence of overall survival benefit, but possible benefit in T3+ tumours. These
      results may be confounded by surgical learning curves and poor surgeon
      compliance. Non-randomised comparisons suggest a possible survival benefit for D2
      in intermediate UICC stages. Observational studies show high 5 year survival and
      low operative mortality after D2 dissection in experienced units, and poor
      results after D1 dissection in non-specialist units. Further studies, with
      precautions to eliminate learning curve effects, contamination and non
      compliance, are needed to evaluate D2 dissection in intermediate stage gastric
      cancer.

PMID- 15495025
TI  - Alpha2 adrenergic agonists for the management of opioid withdrawal.
AB  - BACKGROUND: Withdrawal (detoxification) is necessary prior to drug-free
      treatment. It may also represent the end point of long-term treatment such as
      methadone maintenance. The availability of managed withdrawal is essential to an
      effective treatment system. OBJECTIVES: To assess the effectiveness of
      interventions involving the use of alpha2 adrenergic agonists (clonidine,
      lofexidine, guanfacine) to manage opioid withdrawal in terms of withdrawal signs
      and symptoms, completion of withdrawal and adverse effects. SEARCH STRATEGY:
      Multiple electronic databases (including MEDLINE, EMBASE, PsycINFO, Australian
      Medical Index, Cochrane Clinical Trials Register) were systematically searched.
      Reference lists of retrieved studies, reviews and conference abstracts were
      handsearched and relevant pharmaceutical companies contacted. SELECTION CRITERIA:
      Controlled trials comparing alpha2 adrenergic agonists with reducing doses of
      methadone, symptomatic medications or placebo, or comparing different alpha2
      adrenergic agonists to modify the signs and symptoms of withdrawal in
      participants who were primarily opioid dependent. DATA COLLECTION AND ANALYSIS:
      One reviewer assessed studies for inclusion and undertook data extraction.
      Inclusion decisions and the overall process were confirmed by consultation
      between all four reviewers. MAIN RESULTS: Twenty-two studies, involving 1709
      participants, were included. Eighteen were randomised controlled trials; for the
      remaining studies allocation was by participant choice in two, one used alternate
      allocation and in one the method of allocation was unclear. Twelve studies
      compared a treatment regime based on an alpha2 adrenergic agonist with one based
      on reducing doses of methadone. Diversity in study design, assessment and
      reporting of outcomes limited the extent of quantitative analysis. For the
      comparison of alpha2 adrenergic agonist regimes with reducing doses of methadone,
      there were insufficient data for statistical analysis, but withdrawal intensity
      appears similar to, or marginally greater with alpha2 adrenergic agonists, while
      signs and symptoms of withdrawal occur and resolve earlier in treatment.
      Participants stay in treatment longer with methadone. No significant difference
      was detected in rates of completion of withdrawal with adrenergic agonists
      compared to reducing doses of methadone, or clonidine compared to lofexidine.
      Clonidine is associated with more adverse effects (low blood pressure, dizziness,
      dry mouth, lack of energy) than reducing doses of methadone. Lofexidine does not
      reduce blood pressure to the same extent as clonidine, but is otherwise similar
      to clonidine. REVIEWERS' CONCLUSIONS: No significant difference in efficacy was
      detected for treatment regimes based on the alpha2 adrenergic agonists clonidine
      and lofexidine, and those based on reducing doses of methadone over a period of
      around 10 days, for the management of withdrawal from heroin or methadone.
      Participants stay in treatment longer with methadone regimes and experience less
      adverse effects. The lower incidence of hypotension makes lofexidine more suited
      to use in outpatient settings than clonidine. There are insufficient data
      available to support a conclusion on the efficacy of other alpha2 adrenergic
      agonists.

PMID- 15495026
TI  - Buprenorphine for the management of opioid withdrawal.
AB  - BACKGROUND: Managed withdrawal (detoxification) is a necessary step prior to drug
      free treatment. It may also represent the end point of long-term opioid
      replacement treatment such as methadone maintenance. The availability of managed
      withdrawal is essential to an effective treatment system. OBJECTIVES: To assess
      the effectiveness of interventions involving the use of buprenorphine to manage
      opioid withdrawal, in terms of withdrawal signs and symptoms, completion of
      withdrawal and adverse effects. SEARCH STRATEGY: Multiple electronic databases
      (including Medline, Embase, PsycINFO, Australian Medical Index, Cochrane Clinical
      Trials Register) were systematically searched to October 2003. Reference lists of
      retrieved studies, reviews and conference abstracts were handsearched. SELECTION
      CRITERIA: Controlled trials comparing buprenorphine with reducing doses of
      methadone, alpha2 adrenergic agonists, symptomatic medications or placebo, or
      comparing different buprenorphine-based regimes, to modify the signs and symptoms
      of withdrawal in participants who were primarily opioid dependent. DATA
      COLLECTION AND ANALYSIS: One reviewer assessed studies for inclusion and
      undertook data extraction. Inclusion decisions and the overall process were
      confirmed by consultation between all three reviewers. Included studies were
      assessed for methodological quality. Meta-analysis was undertaken where possible,
      with sensitivity analyses used to assess the impact of methodological quality.
      MAIN RESULTS: Thirteen studies (10 RCTs), involving 744 participants, met the
      criteria for inclusion in the review. Seven studies compared buprenorphine with
      clonidine; 3 compared buprenorphine with methadone; 1 compared buprenorphine with
      oxazepam; 2 compared rapid and slow rates of tapering buprenorphine dose; 1
      compared 3 different starting doses of buprenorphine. For groups treated with
      buprenorphine, withdrawal severity was less than that in groups treated with
      clonidine; peak severity was similar to those treated with methadone, but
      withdrawal symptoms may resolve more quickly with buprenorphine. Withdrawal is
      probably more severe when doses are tapered rapidly following a period of
      maintenance treatment. Buprenorphine is associated with fewer adverse effects
      than clonidine, and completion of withdrawal is significantly more likely with
      buprenorphine (Relative Risk 1.35, 95% confidence interval 1.13, 1.62). In the
      two available studies, there was no statistically significant difference in rates
      of completion of withdrawal for buprenorphine compared to methadone in reducing
      doses. Completion of withdrawal following buprenorphine maintenance treatment may
      be more likely when doses are reduced gradually. REVIEWERS' CONCLUSIONS:
      Buprenorphine is more effective than clonidine for the management of opioid
      withdrawal. There appears to be no significant difference between buprenorphine
      and methadone in terms of completion of withdrawal, but withdrawal symptoms may
      resolve more quickly with buprenorphine. Many aspects of treatment protocol and
      relative effectiveness need to be investigated further in order to determine the
      most effective way of using buprenorphine to manage opioid withdrawal.

PMID- 15495027
TI  - Short-term treatment with proton pump inhibitors, H2-receptor antagonists and
      prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy
      negative reflux disease.
AB  - BACKGROUND: Heartburn affects 25% of the adult population on a monthly basis and
      represents the core symptom of gastro-oesophageal reflux disease (GORD).
      Treatment is readily available and puts a large demand on healthcare budgets. A
      majority of GORD patients show no endoscopic abnormalities and in daily practice
      most patients are treated empirically. OBJECTIVES: Summarise, quantify and
      compare the efficacy of the short-term use of proton pump inhibitors (PPI), H2
      receptor antagonists (H2RA) and prokinetics in adults with GORD and endoscopy
      negative reflux disease (ENRD). SEARCH STRATEGY: We searched the Cochrane Central
      Register of Controlled Trials (The Cochrane Library Issue 4, 2003), MEDLINE
      (January 1966 to December 2003), EMBASE (January 1988 to December 2003).
      SELECTION CRITERIA: Randomised controlled trials focussing on symptomatic outcome
      after short-term treatment for GORD using proton pump inhibitors, H2-receptor
      antagonists or prokinetic agents. Participants had to be classifiable in the
      empirical treatment group (no endoscopy used in treatment allocation) or in the
      endoscopy negative reflux disease group (no endoscopic signs of erosive
      oesophagitis). DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed
      trial quality and extracted data. MAIN RESULTS: Twenty-seven trials (8402
      participants) were included: thirteen in the empirical treatment group, ten in
      the ENRD group and four in both. In empirical treatment of GORD the relative risk
      (RR) for heartburn remission in placebo-controlled trials for PPI was 0.37 (two
      trials, 95% confidence interval (CI) 0.32 to 0.44), for H2RAs 0.77 (two trials,
      95% CI 0.60 to 0.99) and for prokinetics 0.86 (one trial, 95% CI 0.73 to 1.01).
      In a direct comparison PPIs were significantly (p < 0.05) more effective than
      H2RAs (five trials, RR 0.69, 95% CI 0.61 to 0.77) and prokinetics (two trials, RR
      0.53, 95% CI 0.32 to 0.87). In treatment of ENRD, RR for heartburn remission for
      PPI versus placebo was 0.68 (six trials, 95% CI 0.59 to 0.78) and for H2RA versus
      placebo was 0.84 (two trials, 95% CI 0.74 to 0.95). The RR for PPI versus H2RA
      was 0.74 (three trials, 95% CI 0.53 to 1.03) and for PPI versus prokinetic 0.72
      (one trial, 95% CI 0.56 to 0.92). REVIEWERS' CONCLUSIONS: The findings in this
      review suggest that antisecretory drugs are effective in the empirical treatment
      of complaints likely to originate from GORD and in treatment of ENRD and
      furthermore that PPIs are superior to H2RAs in empirical treatment of typical
      GORD symptoms.

PMID- 15495028
TI  - Prophylactic anastomotic drainage for colorectal surgery.
AB  - BACKGROUND: There is little agreement on prophylactic use of drains in
      anastomoses in elective colorectal surgery despite many randomized clinical
      trials. Results of these trials are contradictory, quality and statistical power
      of these individual studies have been questioned. Once anastomotic leakage has
      occurred it is generally agreed that drains should be used for therapeutic
      purposes. However, on prophylactic use no such agreement exists. OBJECTIVES:
      Comparison of safety and effectiveness of routine drainage and non-drainage
      regimes after colorectal surgery. The following hypothesis was tested: The use of
      prophylactic anastomotic drainage after elective colorectal surgery does not
      prevent development of complications. SEARCH STRATEGY: The studies were
      identified from CINAHL, EMBASE, LILACS, MEDLINE, Controlled Clinical Trials
      Database, Trials Register of the Cochrane Colorectal Cancer Group, reference
      lists. SELECTION CRITERIA: Randomized controlled trials comparing drainage with
      non-drainage regimes after anastomoses in elective colorectal surgery were
      reviewed. Outcome measures were: 1. mortality; 2. clinical anastomotic
      dehiscence; 3. radiological anastomotic dehiscence; 4. wound infection; 5.
      reoperation; 6. extra-abdominal complications. DATA COLLECTION AND ANALYSIS: Data
      were independently extracted and cross-checked by the two reviewers. The
      methodological quality of each trial was assessed. Details of the randomization
      (generation and concealment), blinding, and the number of patients lost to follow
      up were recorded. The RCTs were stratified based on experimental group, according
      to clinical homogeneity (external validity). MAIN RESULTS: Of the 1140 patients
      enrolled (6 RCTs), 573 were allocated for drainage and 567 for no drainage. The
      patients assigned to the drainage group compared with the ones assigned to non
      drainage group showed: a) Mortality: 3% (18 of 573 patients) compared with 4% (25
      of 567 patients); b) Clinical anastomotic dehiscence: 2% (11 of 522 patients)
      compared with 1% (7 of 519 patients); c) Radiological anastomotic dehiscence: 3%
      (16 of 522 patients) compared with 4% (19 of 519 patients); d) Wound infection:
      5% (29 of 573 patients) compared with 5% (28 of 567 patients); e) Reintervention:
      6% (34 of 542 patients) compared with 5% (28 of 539 patients); f) Extra abdominal
      complications: 7% (34 of 522 patients) compared with 6% (32 of 519 patients).
      REVIEWERS' CONCLUSIONS: There is insufficient evidence showing that routine
      drainage after colorectal anastomoses prevents anastomotic and other
      complications.

PMID- 15495029
TI  - Concurrent chemoradiotherapy in non-small cell lung cancer.
AB  - BACKGROUND: In a previous meta-analysis of adjuvant chemotherapy in NSCLC there
      was a 13% reduction in the risk of death in patients receiving radical
      radiotherapy. This overview specifically excluded trials in which chemotherapy
      and radiotherapy were given concurrently (NSCLCCG 1995). The use of concurrent
      chemotherapy and radiotherapy might be seen as a way of increasing the
      effectiveness of radiotherapy at the same time as reducing the risks of
      metastatic disease by using chemotherapy. OBJECTIVES: To determine the
      effectiveness of concurrent chemoradiotherapy as compared to radiotherapy alone
      with regard to local control and overall survival; and to determine whether the
      addition of concurrent chemotherapy results in an altered risk of treatment
      related morbidity. To compare concurrent with sequential chemoradiotherapy.
      SEARCH STRATEGY: Electronic search of the Cochrane Central Register of Controlled
      Trials (CENTRAL), MEDLINE and EMBASE with identification of further studies from
      references cited in the initial identified studies. SELECTION CRITERIA:
      Randomised trials of patients with stage I-III non-small cell lung cancer (NSCLC)
      undergoing radical radiotherapy and randomised to receive concurrent
      chemoradiotherapy versus radiotherapy alone, or concurrent versus sequential
      chemoradiotherapy. DATA COLLECTION AND ANALYSIS: Identified trials were reviewed
      independently by both reviewers. Relative risks (calculated according to a random
      effects model) were determined with respect to overall survival, progression-free
      survival and treatment morbidity. MAIN RESULTS: Fourteen randomised studies
      (including 2393 patients) of concurrent chemoradiotherapy versus radiotherapy
      alone met the inclusion criteria. In a meta-analysis there was a reduction in
      risk of death at two years (relative risk (RR) 0.93; 95% CI 0.88 to 0.98; P =
      0.01). Similar improvements in two-year locoregional progression-free survival
      (RR 0.84; 95% CI 0.72 to 0.98; P = 0.03) and progression-free survival at any
      site (RR 0.90; 95% CI 0.84 to 0.97; P = 0.005) were also seen in those receiving
      concurrent chemoradiotherapy. Subgroup analysis suggested the possibility of a
      greater benefit from regimens which incorporated once daily fractionation of
      radiotherapy or a higher total chemotherapy dose. The incidence of acute
      oesophagitis, neutropenia and anaemia were significantly increased by concurrent
      chemoradiotherapy. In a meta-analysis of three trials of concurrent versus
      sequential chemoradiotherapy there was a significant reduction in the risk of
      death at two years with concurrent treatment (RR 0.86; 95% CI 0.78 to 0.95; P =
      0.003) but potentially at the expense of toxicity, although data was incomplete.
      REVIEWERS' CONCLUSIONS: With concurrent chemoradiotherapy there was a 14%
      reduction in risk of death at two years compared to sequential chemoradiotherapy,
      and a 7% reduction compared to radiotherapy alone. In both cases there was some
      increase in acute oesophagitis. Caution is advised in adopting concurrent
      chemoradiotherapy as the standard of care because of uncertainties about the true
      magnitude of benefit in comparison with sequential chemoradiotherapy. With short
      follow up and uncertainties about toxicity in the identified studies, the optimal
      chemotherapy regimen remains uncertain. The confounding effects of treatment
      related anaemia and gaps in treatment due to toxicity require further
      investigation.

PMID- 15495030
TI  - Effectiveness of intermediate care in nursing-led in-patient units.
AB  - BACKGROUND: The Nursing led inpatient Unit (NLU) is one of a range of services
      that have been considered in order to manage more successfully the transition
      between hospital and home for patients with extended recovery times. OBJECTIVES:
      To determine whether nursing-led inpatient units are effective in preparing
      patients for discharge from hospital compared to usual inpatient care. SEARCH
      STRATEGY: We searched The Cochrane Library, the Specialized Register of the
      Cochrane Effective Practice and Organisation of Care (EPOC) group, MEDLINE,
      CINAHL, EMBASE, BNI and HMIC databases. Citation searches were undertaken on the
      science and social science citation indices. Authors were contacted to identify
      additional data. SELECTION CRITERIA: Controlled trials and interrupted time
      series designs that compared the NLU to usual inpatient care managed by doctors.
      Patients over 18 years of age following an acute hospital admission for a
      physical health condition. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently extracted data and assessed study quality. MAIN RESULTS: Ten random
      or quasi-random controlled trials reported on a total of 1896 patients. There was
      no statistically significant effect on inpatient mortality ( OR 1.10, 95% CI 0.56
      to 2.16) or mortality to longest follow up (OR 0.92, 95% CI 0.65 to 1.29) but
      higher qaulity studies showed a larger non-significant increase in inpatient
      mortality (OR 1.52, 95% CI 0.86 to 2.68). Discharge to institutional care was
      reduced for the NLU (OR 0.44 95% CI 0.22 to 0.89) and functional status at
      discharge increased (SMD 0.37, 95% CI 0.20 to 0.54) but there was a near
      significant increase in inpatient stay (WMD 5.13 days 95% CI -0.5 days to 10.76
      days). Early readmissions were reduced (OR 0.52 95% CI 0.34 to 0.80). One study
      compared a NLU for the chronically critically ill with ICU care. Mortality (OR
      0.62 95% CI 0.35 to 1.10) and length of inpatient stay differ did not differ (WMD
      2 days, 95% CI 10.96 to -6.96 days). Early readmissions were reduced (OR 0.33 95%
      CI 0.12 to 0.94). Costs of care on the NLU were higher for UK studies but lower
      for US based studies. REVIEWERS' CONCLUSIONS: There is some evidence that
      patients discharged from a NLU are better prepared for discharge but it is
      unclear if this is simply a product of an increased length of inpatient stay. No
      statistically significant adverse effects were noted but the possibility of
      increased early mortality cannot be discounted. More research is needed.

PMID- 15495031
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 itched less and expressed a preference for Zemaphyte. 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. REVIEWERS' 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- 15495032
TI  - Clotiapine for acute psychotic illnesses.
AB  - BACKGROUND: Acute psychotic illnesses, especially when associated with agitated
      or violent behaviour, require urgent pharmacological tranquillisation or
      sedation. Clotiapine, a dibenzothiazepine neuroleptic, is being used for this
      purpose in several countries. OBJECTIVES: To estimate the effects of clotiapine
      when compared to other 'standard' or 'non-standard' treatments for acute
      psychotic illnesses in controlling disturbed behaviour and reducing psychotic
      symptoms. SEARCH STRATEGY: We updated previous searches by searching the Cochrane
      Schizophrenia Group Register (April 2004) SELECTION CRITERIA: The review included
      randomised clinical trials comparing clotiapine with any other treatment for
      people with acute psychotic illnesses. DATA COLLECTION AND ANALYSIS: Relevant
      studies were selected for inclusion, their quality was assessed and data
      extracted. Data were excluded where more than 50% of participants in any group
      were lost to follow up. For binary outcomes we calculated a standard estimation
      of the risk ratio (RR) and its 95% confidence interval (CI). For continuous
      outcomes, endpoint data were preferred to change data. Non-skewed data from valid
      scales were summated using a weighted mean difference (WMD). MAIN RESULTS: We
      identified five relevant trials. None compared clotiapine with placebo, but
      control drugs were either antipsychotics (chlorpromazine, perphenazine,
      trifluoperazine and zuclopenthixol acetate) or benzodiazepines (lorazepam).
      Versus the antipsychotics, the results for 'no important global improvement' did
      not suggest clotiapine to be superior, or inferior, to chlorpromazine,
      perphenazine, or trifluoperazine (n = 83, 3 RCTs, RR 0.82 CI 0.22 to 3.05, I
      squared 58%). Use of clotiapine when compared with chlorpromazine did change the
      proportion of people ready for hospital discharge by the end of the study (n =
      49, 1 RCT, RR 1.04 95%CI 0.96 to 2.12). Overall, attrition rates were low. No
      significant difference was found for those allocated to clotiapine compared with
      people randomised to other antipsychotics (n = 121, RR 2.26 95%CI 0.40 to 13).
      Weak data suggests that clotiapine may result in less need for antiparkinsonian
      treatment compared with zuclopenthixol acetate (n = 38, RR 0.43 95%CI 0.02 to
      0.98). Compared with lorazepam, clotiapine, when used to control
      aggressive/violent outbursts for people already treated with haloperidol, did not
      significantly improve mental state (WMD -3.36 95%CI -8.09 to 1.37). We could not
      pool much data due to skew or inadequate presentation of results. Economic
      outcomes and satisfaction with care were not addressed. REVIEWERS' CONCLUSIONS:
      We found no evidence to support the use of clotiapine in preference to other
      'standard' or 'non-standard' treatments for management of people with acute
      psychotic illness. All trials in this review have important methodological
      problems. We do not wish to discourage clinicians from using clotiapine in the
      psychiatric emergency, but well-designed, conducted and reported trials are
      needed to properly determine the efficacy of this drug.

PMID- 15495033
TI  - Prophylactic mastectomy for the prevention of breast cancer.
AB  - BACKGROUND: Breast cancer is the most common cancer and the second most common
      cause of cancer-related death among North American and Western European women.
      Recent progress in understanding the genetic basis of breast cancer, along with
      rising incidence rates, have resulted in increased interest in prophylactic
      mastectomy as a method of preventing breast cancer, particularly in those with
      familial susceptibility. OBJECTIVES: The primary objective was to determine
      whether prophylactic mastectomy reduces death from any cause in women who have
      never had breast cancer and in women who have a history of breast cancer in one
      breast. The secondary objective was to examine the effect of prophylactic
      mastectomy on other endpoints including breast cancer incidence, breast cancer
      mortality, disease-free survival, physical morbidity, and psychosocial outcomes.
      SEARCH STRATEGY: Electronic searches were performed in the Cochrane Central
      Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Cancerlit, and the
      Science Citation Index. SELECTION CRITERIA: Inclusion criteria were studies in
      English of any design type including randomized or nonrandomized controlled
      trials, cohort studies, case-control studies, and case series with at least ten
      participants. Participants included women at risk for breast cancer in at least
      one breast. Interventions included all types of mastectomy performed for the
      purpose of preventing breast cancer, including subcutaneous mastectomy, total or
      simple mastectomy, modified radical mastectomy, and radical mastectomy. DATA
      COLLECTION AND ANALYSIS: Information on patients, interventions, methods, and
      results were extracted by at least two independent reviewers. Methodological
      quality was assessed based on how well each study minimized potential selection
      bias, performance bias, detection bias, and attrition bias. Data for each study
      were summarized descriptively; quantitative meta-analysis was not feasible due to
      heterogeneity of study designs and insufficient reporting. Data were analyzed
      separately for bilateral prophylactic mastectomy (BPM) and contralateral
      prophylactic mastectomy (CPM). MAIN RESULTS: Twenty-three studies, including more
      than 4,000 patients, met inclusion criteria. No randomized or nonrandomized
      controlled trials were found. Most studies were either case series or cohort
      studies. All studies had methodological limitations, with the most common source
      of potential bias being systematic differences between the intervention and
      comparison groups that could potentially be associated with a particular outcome.
      Thirteen studies assessed the effectiveness of BPM. No study assessed all-cause
      mortality after BPM. All studies reporting on incidence of breast cancer and
      disease-specific mortality reported reductions after BPM. Nine studies assessed
      psychosocial measures; most reported high levels of satisfaction with the
      decision to have prophylactic mastectomy (PM) but more variable satisfaction with
      cosmetic results. Only one study assessed satisfaction with the psychological
      support provided by healthcare personnel during risk counseling and showed that
      more women were dissatisfied than satisfied with the support they received in the
      healthcare setting. Worry over breast cancer was significantly reduced after BPM
      when compared both to baseline worry levels and to the groups who opted for
      surveillance rather than BPM. Three studies reported body image/feelings of
      femininity outcomes, and all reported that a substantial minority (about 20%)
      reported BPM had adverse effects on those domains. Six studies assessed
      contralateral prophylactic mastectomy. Studies consistently reported reductions
      in contralateral incidence of breast cancer but were inconsistent about
      improvements in disease-specific survival. Only one study attempted to control
      for multiple differences between intervention groups, and this study showed no
      overall survival advantage for CPM at 15 years. Two case series were exclusively
      focused on adverse events from prophylactic mastectomy with reconstruction, and
      both reported rates of unanticipated re-operations from 30% to 49%. REVIEWERS'
      CONCLUSIONS: While published observational studies demonstrated that BPM was
      effective in reducing both the incidence of, and death from, breast cancer, more
      rigorous prospective studies (ideally randomized trials) are needed. The studies
      need to be of sufficient duration and make better attempts to control for
      selection biases to arrive at better estimates of risk reduction. The state of
      the science is far from exact in predicting who will get or who will die from
      breast cancer. By one estimate, most of the women deemed high risk by family
      history (but not necessarily BRCA 1 or 2 mutation carriers) who underwent these
      procedures would not have died from breast cancer, even without prophylactic
      surgery. Therefore, women need to understand that this procedure should be
      considered only among those at very high risk of the disease. For women who had
      already been diagnosed with a primary tumor, the data were particularly lacking
      for indications for contralateral prophylactic mastectomy. While it appeared that
      contralateral mastectomy may reduce the incidence of cancer in the contralateral
      breast, there was insufficient evidence about whether, and for whom, CPM actually
      improved survival. Physical morbidity is not uncommon following PM, and many
      women underwent unanticipated re-operations (usually due to problems with
      reconstruction); however, these data need to be updated to reflect changes in
      surgical procedures and reconstruction. Regarding psychosocial outcomes, women
      generally reported satisfaction with their decisions to have PM but reported
      satisfaction less consistently for cosmetic outcomes, with diminished
      satisfaction often due to surgical complications. Therefore, physical morbidity
      and post-operative surgical complications were areas that should be considered
      when deciding about PM. With regard to emotional well-being, most women recovered
      well postoperatively, reporting reduced cancer worry and showing reduced
      psychological morbidity from their baseline measures; exceptions also have been
      noted. Of the psychosocial outcomes measured, body image and feelings of
      femininity were the most adversely affected.

PMID- 15495034
TI  - Thrombolysis for acute deep vein thrombosis.
AB  - BACKGROUND: Standard treatment for deep vein thrombosis (DVT) aims to reduce
      immediate complications. Use of thrombolysis or clot dissolving drugs could
      reduce the long-term complications of post-thrombotic syndrome (pain, swelling,
      skin discolouration, or venous ulceration) in the affected leg. OBJECTIVES: To
      determine the efficacy and safety of thrombolysis for DVT. SEARCH STRATEGY:
      Publications describing randomised controlled trials (RCTs) of thrombolysis
      versus anticoagulation for acute DVT were sought through electronic searches of
      the Cochrane Peripheral Vascular Diseases trials register (last searched April
      2004) and the Cochrane Central Register of Controlled Trials (CENTRAL) (last
      searched The Cochrane Library Issue 2, 2004). Additional trials were identified
      by reviewing reference lists of papers. There were no restrictions for language.
      SELECTION CRITERIA: RCTs examining thrombolysis versus anticoagulation for acute
      DVT and/or calf vein thrombosis were considered. DATA COLLECTION AND ANALYSIS:
      One reviewer (LIW) selected trials, extracted data and assessed study quality,
      with checking at all stages by the other reviewer (MPA). Where required,
      additional information was sought from trialists. MAIN RESULTS: Twelve studies
      were included. Complete clot lysis occurred significantly more often in the
      treatment group in early follow up, (relative risk (RR) 0.24; 95% confidence
      interval (CI) 0.07 to 0.82), and in late follow up, (RR 0.37; 95 % CI 0.25 to
      0.54). A similar effect was also seen for any degree of improvement in venous
      patency. Significantly less post-thrombotic syndrome occurred in those receiving
      thrombolysis, (RR 0.66; 95 % CI 0.47 to 0.94). Leg ulceration was reduced
      although the data were limited by small numbers, (RR 0.53; 95 % CI 0.12 to 2.43).
      Venous function was improved at late follow up, but not significantly (RR 0.43;
      95 % CI 0.06 to 3.17)Out of 668 patients, those receiving thrombolysis had
      significantly more bleeding complications, (RR 1.73; 95 % CI 1.04 to 2.88). Two
      strokes occurred in the treatment group (RR 1.70; 95 % CI 0.21 to 13.70). The
      incidence of bleeding appears to have reduced over time with the introduction of
      stricter selection criteria. There was no significant effect on mortality
      detected in either early or late follow up. Data on occurrence of pulmonary
      embolism (PE) and recurrent DVT were inconclusive. REVIEWERS' CONCLUSIONS:
      Thrombolysis appears to offer advantages in terms of reducing post-thrombotic
      syndrome and maintaining venous patency after DVT. Use of strict eligibility
      criteria has improved the safety and acceptability of this treatment. The optimum
      drug, dose and route of administration have yet to be determined.

PMID- 15495035
TI  - Physiotherapy interventions for ankylosing spondylitis.
AB  - BACKGROUND: Ankylosing spondylitis (AS) is a chronic, inflammatory rheumatic
      disease. Due to the consequences of the disease, physiotherapy is considered to
      be an important part of the overall management of AS. OBJECTIVES: The objective
      of this review was to summarise the available scientific evidence on the
      effectiveness of physiotherapy interventions in the management of AS. SEARCH
      STRATEGY: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL), MEDLINE, EMBASE, AMED, CINAHL and PEDro up to February 2004 for all
      relevant publications, without any language restrictions. The reference lists of
      relevant articles were checked and the authors of included articles were
      contacted. SELECTION CRITERIA: We included randomised and quasi-randomised
      studies with patients classified by the AS New York criteria and where at least
      one of the comparison groups received some kind of physiotherapy. The main
      outcomes of interest were pain, stiffness, spinal mobility, physical function and
      patient global assessment. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently selected trials for inclusion, extracted data and assessed trial
      quality. Investigators were contacted to obtain missing information. MAIN
      RESULTS: Six trials with a total of 561 participants were included in this
      updated review as compared to three trials and 241 patients in the previous
      version. Two trials compared individualised home exercise programs with no
      intervention and reported low quality evidence for effects in spinal mobility
      (relative percentage differences (RPD) 37%) and physical function, in favour of
      the home exercise program. Three trials compared supervised group physiotherapy
      with an individualised home-exercise program and reported moderate quality
      evidence for small differences in spinal mobility (RPD 18%) and patient global
      assessment in favour of supervised group exercises. Finally, in one study a three
      week inpatient spa-exercise therapy followed by 37 weeks of weekly outpatient
      group physiotherapy (without spa) was compared with weekly outpatient group
      physiotherapy alone; there was moderate quality evidence for effects in pain (RPD
      18%), physical function (RPD 24%) and patient global assessment (RPD 29%), in
      favour of the combined spa-exercise therapy. REVIEWERS' CONCLUSIONS: The results
      of this review suggest that a home exercise program is better than no
      intervention, supervised group physiotherapy is better than home exercises, and
      that combined inpatient spa-exercise therapy followed by supervised outpatient
      weekly group physiotherapy is better than weekly group physiotherapy alone. The
      tendency toward positive effects of physiotherapy in the management of AS calls
      for further research in this field. New trials should also address other
      physiotherapy interventions commonly used in clinical practice.

PMID- 15495036
TI  - Antioxidant treatment for amyotrophic lateral sclerosis / motor neuron disease.
AB  - BACKGROUND: Free radical accumulation and oxidative stress have been proposed as
      contributing to the progression of amyotrophic lateral sclerosis (or motor neuron
      disease). A range of antioxidant medications are available, and have been
      studied. OBJECTIVES: To examine the effects of antioxidant medication in the
      treatment of people with amyotrophic lateral sclerosis. SEARCH STRATEGY: We
      searched the Cochrane Neuromuscular Disease Group trials register (July 2003),
      MEDLINE (from January 1966 to July 2003), EMBASE (from January 1980 to July 2003)
      and other sources. SELECTION CRITERIA: All randomized or quasi-randomized
      controlled trials of antioxidant treatment for amyotrophic lateral sclerosis.
      DATA COLLECTION AND ANALYSIS: The reviewers independently applied the selection
      criteria, assessed study quality and two reviewers performed independent data
      extraction. MAIN RESULTS: The search identified 21 studies for consideration but
      only eight studies met the inclusion criteria. Only two studies used our
      predetermined primary outcome measure, (survival at 12 months treatment).
      Sufficient data were available from three studies to allow analysis of the
      primary outcome measure, and a meta-analysis was performed. In the individual
      studies no significant effect was observed of vitamin E 500 mg twice daily;
      acetylcysteine 50 mg/kg daily subcutaneous infusion; or a combination of L
      methionine 2 g, vitamin E 400 International Units, and selenium 3 x 10-5g three
      times daily (Alsemet). No significant effect on the primary outcome measure was
      observed in a meta-analysis of antioxidants in general when combining the
      results. No significant differences were demonstrated in secondary outcome
      measures. REVIEWERS' CONCLUSIONS: There is insufficient evidence of efficacy of
      individual antioxidants, or antioxidants in general, in the treatment of people
      with amyotrophic lateral sclerosis. One study reported a mild positive effect,
      but this was not supported by the analysis we used. Generally the studies were
      poorly designed, and underpowered, with low numbers of participants and of short
      duration. Further well-designed trials of medications such as vitamin C and E are
      unlikely to be performed. If future trials of antioxidant medications are
      performed, careful attention should be given to sample size, outcome measures,
      and duration of the trial. The high tolerance and safety, and relatively low cost
      of vitamins C and E, and other considerations related to the lack of other
      effective treatments for amyotrophic lateral sclerosis, explain the continuing
      use of these vitamins by physicians and patients. While there is no substantial
      clinical trial evidence to support their clinical use, there is no clear
      contraindication.

PMID- 15495037
TI  - Droperidol for acute psychosis.
AB  - BACKGROUND: People suffering from acute psychotic illnesses, especially those
      associated with agitated or violent behaviour, may require urgent pharmacological
      tranquillisation or sedation. Droperidol, a butyrophenone neuroleptic, has been
      used for this purpose in several countries. OBJECTIVES: To estimate the effects
      of droperidol compared to other treatments for controlling disturbed behaviour
      and reducing psychotic symptoms for people with suspected acute psychotic
      illnesses. SEARCH STRATEGY: We updated previous searches by searching the
      Cochrane Schizophrenia Group Register (September 2003). References of all
      identified studies were searched for further trial citations and authors of
      trials were contacted. Twenty-one other databases were also searched as part of a
      broader project and this composite database was searched for this review. This
      was supplemented by hand searching reference lists and contacting both the
      pharmacological industry and relevant authors. SELECTION CRITERIA: The review
      included randomised controlled trials comparing droperidol to any other treatment
      for people with suspected acute psychotic illnesses, including schizophrenia,
      schizoaffective disorder, mixed affective disorders, the manic phase of bipolar
      disorder or a brief psychotic episode. DATA COLLECTION AND ANALYSIS: Relevant
      studies were selected for inclusion, their quality was assessed and data
      extracted. Data were excluded when more than 50% of participants were lost to
      follow up. For binary outcomes, standard estimates of risk ratio (RR) and the
      corresponding 95% confidence intervals (CI) were calculated. Where possible,
      weighted number needed to treat or harm statistics (NNT, NNH), and the
      corresponding 95% confidence intervals (CI), were calculated. MAIN RESULTS: We
      identified only two relevant trials. One additional study focused on outcomes at
      30 days rather than at a few hours. One small (n = 41) randomised trial compared
      intravenous (iv) droperidol (10 mg) with iv placebo and found that people
      allocated to droperidol were significantly less likely to need additional
      injections of another drug, haloperidol, in the first few minutes (n = 41, RR
      0.37 CI 0.2 to 0.7, NNT 2 CI 1 to 10) compared to those given placebo. By 90
      minutes this difference was still evident but not statistically significant (RR
      0.46 CI 0.2 to 1.2). When 5 mg intramuscular (im) droperidol was compared with 5
      mg im haloperidol, those given droperidol were also less likely to need
      additional injections by 30 minutes, than those given haloperidol, but this
      result was not statistically significant (n = 27, RR 0.45 CI 0.2 to 1.01). One
      person out of the 16 given haloperidol experienced a mild dystonic reaction
      (muscle spasms or abnormal contractions), while none of the 11 people allocated
      to droperidol were reported to have experienced adverse effects. REVIEWERS'
      CONCLUSIONS: This is an important, and surprisingly under-researched, area. To
      date, use of droperidol for emergency situations has been justified by experience
      rather than evidence from well conducted and reported randomised trials, but, as
      world reserves diminish, droperidol will no longer be a treatment option.

PMID- 15495038
TI  - In-hospital care pathways for stroke.
AB  - BACKGROUND: Stroke care pathways have the potential to promote organised and
      efficient patient care that is based on best evidence and guidelines, but
      evidence to support their use is unclear. OBJECTIVES: We aimed to assess the
      effects of care pathways, compared with standard medical care, among patients
      with acute stroke who had been admitted to hospital. SEARCH STRATEGY: We searched
      the Cochrane Stroke Group Trials Register (last searched in June 2003), the
      Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2,
      2003), MEDLINE (1975 to June 2003), EMBASE (1980 to June 2003), CINAHL (1982 to
      June 2003), ISI Proceedings: Science & Technology (1990 to November 2003), and
      HealthSTAR (1994 to May 2001). We also handsearched the Journal of Integrated
      Care Pathways (2001 to 2003), formerly Journal of Managed Care (1997 to 1998) and
      Journal of Integrated Care (1998 to 2001). Reference lists of articles were
      searched. SELECTION CRITERIA: We considered randomised controlled trials and non
      randomised studies that compared care pathway care with standard medical care.
      DATA COLLECTION AND ANALYSIS: One reviewer selected studies for inclusion and the
      other independently checked the decisions. Two reviewers independently assessed
      the methodological quality of the studies. One reviewer extracted the data and
      the other checked the extracted data. MAIN RESULTS: Three randomised controlled
      trials (340 patients) and 12 non-randomised studies (4081 patients) were
      included. There was significant statistical heterogeneity in the analysis of many
      of the outcomes. We found no significant difference between care pathway and
      control groups in terms of death or discharge destination. Patients managed with
      a care pathway were: (a) more dependent at discharge (P = 0.04); (b) less likely
      to suffer a urinary tract infection (Odds Ratio (OR) 0.51, 95% Confidence
      Interval (CI) 0.34 to 0.79); (c) less likely to be readmitted (OR 0.11, 95% CI
      0.03 to 0.39); and (d) more likely to have neuroimaging (OR 2.42, 95% CI 1.12 to
      5.25). Evidence from randomised trials suggested that patient satisfaction and
      quality of life were significantly lower in the care pathway group (P = 0.02 and
      P < 0.005 respectively). REVIEWERS' CONCLUSIONS: Use of stroke care pathways may
      be associated with positive and negative effects. Since most of the results have
      been derived from non-randomised studies, they are likely to be influenced by
      potential biases and confounding factors. There is currently insufficient
      supporting evidence to justify the routine implementation of care pathways for
      acute stroke management or stroke rehabilitation.

PMID- 15495039
TI  - Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot
      flushes.
AB  - BACKGROUND: Hot flushes and night sweats are common symptoms experienced by
      menopausal women. Hormone therapy (HT), containing oestrogens alone or oestrogens
      together with progestogens in a cyclic or continuous regimen, is often
      recommended for their alleviation. OBJECTIVES: To examine the effect of oral HT
      compared to placebo on these vasomotor symptoms and the risk of early onset side
      effects. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders Group and
      Subfertility Group trials register (searched May 2002). This register is based on
      regular searches of MEDLINE, EMBASE, CINAHL, the Cochrane Central Register of
      Controlled Trials (CENTRAL), PsycINFO, the handsearching of 20 relevant journals
      and conference proceedings, and searches of several key grey literature sources.
      We also contacted all relevant pharmaceutical companies, The Journal of the
      International Menopause Society and Climacteric. SELECTION CRITERIA: Double
      blind, randomised, placebo-controlled trials of oral HT for at least three months
      duration. DATA COLLECTION AND ANALYSIS: Study quality and outcome data were
      assessed independently. Random effects models were considered appropriate due to
      the variety of trial methodologies. The meta-analyses were explored for
      sensitivity to trial quality and therapy duration. Symptom frequency and severity
      were assessed separately, together with withdrawals and side-effects. Frequency
      data were analysed using the Weighted Mean Difference (WMD) between treatment and
      placebo outcomes. For severity data, odds ratios were estimated from the
      proportional odds model. From 115 references originally identified, 24 trials
      meeting the selection criteria were included in the review. Study participants
      totaled 3,329. Trial duration ranged from three months to three years. MAIN
      RESULTS: There was a significant reduction in the weekly hot flush frequency for
      HT compared to placebo (WMD -17.92, 95% CI -22.86 to -12.99). This was equivalent
      to a 75% reduction in frequency (95% CI 64.3 to 82.3) for HT relative to placebo.
      Symptom severity was also significantly reduced compared to placebo (OR 0.13, 95%
      CI 0.07 to 0.23). Withdrawal for lack of efficacy occurred significantly more
      often on placebo therapy (OR 10.51, 95% CI 5.00 to 22.09). Withdrawal for adverse
      events, commonly breast tenderness, oedema, joint pain and psychological
      symptoms, was not significantly increased (OR 1.25, 95% CI 0.83 to 1.90),
      although the occurrence of any adverse events was significantly increased for HT
      (OR 1.41, 95% CI 1.00 to 1.99). In women who were randomised to placebo
      treatment, a 57.7% (95% CI 45.1 to 67.7) reduction in hot flushes was observed
      between baseline and end of study. REVIEWERS' CONCLUSIONS: Oral HT is highly
      effective in alleviating hot flushes and night sweats. Therapies purported to
      reduce such symptoms must be assessed in blinded trials against a placebo or a
      validated therapy because of the large placebo effect seen in well conducted
      randomised controlled trials, and also because during menopause symptoms may
      fluctuate and after menopause symptoms often decline. Withdrawals due to side
      effects were only marginally increased in the HT groups despite the inability to
      tailor HT in these fixed dose trials. Comparisons of hormonal doses, product
      types or regimens require analysis of trials with these specific "within study"
      comparisons.

PMID- 15495040
TI  - Mediastinal chest drain clearance for cardiac surgery.
AB  - BACKGROUND: Cardiac tamponade may occur following cardiac surgery as a result of
      blood or fluid collecting in the pericardial space compressing the heart and
      reducing cardiac output. Mediastinal chest drains (including pericardial drains)
      are inserted as standard post-operative practice following cardiac surgery to
      assist the clearance of blood from the pericardial space and to prevent cardiac
      tamponade. To prevent chest tubes from blocking and so causing tamponade nurses
      manipulate them to prevent or remove clots. Manipulation methods including
      milking, stripping, fanfolding and tapping may be applied to the tubes to keep
      them from blocking. Evidence is required as to the safest and most effective
      means of preventing chest tube blockage and preventing cardiac tamponade.
      OBJECTIVES: To compare different methods of chest drain clearance (i.e. varying
      levels of suction or suction in combination with milking, stripping, fanfolding
      and tapping of chest drains) in preventing cardiac tamponade in patients
      following cardiac surgery. SEARCH STRATEGY: Over both the initial review and the
      2004 revision, we searched the Cochrane Heart Group trials register, the Cochrane
      Controlled Trials Register (CCTR) (Issue 4, 2003) The Cochrane Database of
      Systematic Reviews (CDSR), the Database of Abstracts of Reviews of Effectiveness
      (DARE), Issue 4, 2003, MEDLINE (1966 to Nov Week 2, 2003), EMBASE (1980 to 2003
      Week 47), CINAHL (1982 to Nov 2003), the Clinical Trials site of the NIH, (USA)
      (24.11.03) and reference lists of articles. SELECTION CRITERIA: Randomised, quasi
      randomised or systematically allocated clinical trials of chest tube manipulation
      methods in adults and children with mediastinal chest drains following cardiac
      surgery were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently
      assessed trial quality and extracted data. Study authors were contacted for
      additional information where required. Adverse effects information was collected
      from the trials. MAIN RESULTS: Three studies with a total of 471 participants
      were included. There was no data, however, which could be included in a meta
      analysis. This was due to inadequate data provision by two of the studies. Where
      adequate data were provided there were no common interventions or outcomes to
      pool. On the basis of single studies there was no evidence of a difference
      between groups on incidence of chest tube blockage, heart rate, cardiac tamponade
      or incidence of surgical re-entry. REVIEWERS' CONCLUSIONS: There are insufficient
      studies which compare differing methods of chest drain clearance to support or
      refute the relative efficacy of the various methods in preventing cardiac
      tamponade. Nor can the need to manipulate chest drains be supported or refuted by
      results from RCT's.

PMID- 15495041
TI  - Dopaminergic agonists for hepatic encephalopathy.
AB  - BACKGROUND: Hepatic encephalopathy may be associated with an impairment of the
      dopaminergic neurotransmission. Dopaminergic agonists may therefore have a
      beneficial effect on patients with hepatic encephalopathy. OBJECTIVES: To
      evaluate the beneficial and harmful effects of dopaminergic agonists for patients
      with hepatic encephalopathy. SEARCH STRATEGY: Trials were identified through The
      Cochrane Hepato-Biliary Group Controlled Trials Register (July 2004), The
      Cochrane Central Register of Controlled Trials (Issue 3, 2004), MEDLINE (1966
      2004/07), EMBASE (1980-2004/07), manual searches of bibliographies and journals,
      authors of trials, and pharmaceutical companies. SELECTION CRITERIA: All
      randomised trials comparing dopaminergic agonists versus placebo or no
      intervention for hepatic encephalopathy. DATA COLLECTION AND ANALYSIS: Trial
      inclusion and data extraction were made independently by two reviewers. Binary
      outcomes are reported as odds ratios (OR) with 95% confidence intervals (CI)
      based on a random effects model. The presence of statistical heterogeneity was
      explored by the chi-squared test with significance set at P < 0.1. Potential
      sources of heterogeneity were explored through subgroup analyses with regard to
      the type of hepatic encephalopathy and type of dopaminergic agonist. MAIN
      RESULTS: Five trials were included. Four trials had low methodological quality.
      Compared with placebo or no treatment, dopaminergic agonists had no significant
      effect on the risk of no improvement (OR 0.33, 95% CI 0.01 to 11.25, two trials,
      80 patients) or mortality (OR 1.11, 95% CI 0.34 to 3.54, four trials, 139
      patients). There was significant heterogeneity (P = 0.09) among trial results on
      the risk of no improvement, but not on mortality (P = 0.19). The treatment
      response was not significantly different with regard to the type of hepatic
      encephalopathy or dopaminergic agonist, but the analyses had very low power to
      detect potential differences. There was a nonsignificant trend that dopaminergic
      agonists may be associated with adverse events (OR 8.33, 95% CI 0.37 to 187.74, 2
      trials, 13 patients). All adverse events (n = 7) occurred in the experimental
      group. REVIEWERS' CONCLUSIONS: This review does not provide evidence that
      dopaminergic agonists are of benefit to patients with acute or chronic hepatic
      encephalopathy, or fulminant hepatic failure. The review is limited by the small
      number of trials performed within this field, the low number of patients
      randomised in each trial, and the low methodological quality of included trials.
      Accordingly, there is also insufficient evidence to exclude a potential
      beneficial effect. Dopaminergic agonists should not be used for hepatic
      encephalopathy, but may be assessed in future randomised clinical trials.

PMID- 15495042
TI  - Physical therapies for reducing and controlling lymphoedema of the limbs.
AB  - BACKGROUND: Lymphoedema is the accumulation of excess fluid in the body caused by
      obstruction of the lymphatic drainage mechanisms. Management involves
      decongesting the reduced lymphatic pathways in order to reduce the size of the
      limb. There is a great deal of debate as to which components of a physical
      treatment programme are the most crucial. OBJECTIVES: To assess the effect of
      physical treatment programmes on: volume, shape, condition and long-term control
      of oedema in lymphoedematous limbs; psycho-social benefits. SEARCH STRATEGY: We
      searched the Cochrane Breast Cancer Group trials register (September 2003), the
      Cochrane Central Register of Controlled Trials (The Cochrane Library Issue
      4,2003), MEDLINE, EMBASE, CINAHL, UnCover, PASCAL, SIGLE, reference lists
      produced by The British Lymphology Society, the National Research Register (NRR)
      and The International Society of Lymphology congress proceedings. SELECTION
      CRITERIA: Randomised controlled clinical trials that tested physical therapies
      with a follow-up period of at least six months. DATA COLLECTION AND ANALYSIS: Two
      blinded reviewers independently assessed trial quality and extracted data . Meta
      analysis was not performed due to the poor quality of the trials. MAIN RESULTS:
      Only three studies involving 150 randomised patients were included. Since none
      studied the same intervention it was not possible to combine the data. One
      crossover study of manual lymph drainage (MLD) followed by self-administered
      massage versus no treatment, concluded that improvements seen in both groups were
      attributable to the use of compression sleeves and that MLD provided no extra
      benefit at any point during the trial. Another trial looked at hosiery versus no
      treatment and had a very high dropout rate, with only 3 out of 14 participants in
      the intervention group finishing the trial and only 1 out of 11 in the control
      group. The authors concluded that wearing a compression sleeve is beneficial. The
      bandage plus hosiery versus hosiery alone trial, concluded that in this mixed
      group of participants bandage plus hosiery resulted in a greater reduction in
      excess limb volume than hosiery alone and this difference in reduction was
      maintained long-term. REVIEWERS' CONCLUSIONS: All three trials have their
      limitations and have yet to be replicated, so their results must be viewed with
      caution. There is a clear need for well-designed, randomised trials of the whole
      range of physical therapies if the best approach to managing lymphoedema is to be
      determined.

PMID- 15495043
TI  - Memantine for dementia.
AB  - BACKGROUND: Alzheimer's disease, vascular and mixed dementia are the three
      commonest forms of dementia affecting older people. There is evidence that the
      excitatory activity of L-glutamate plays a role in the pathogenesis of
      Alzheimer's disease and in the damage from an ischaemic stroke. A low affinity
      antagonist to N-Methyl-D-aspartate (NMDA) type receptors, such as memantine, may
      prevent excitatory amino acid neurotoxicity without interfering with the
      physiological actions of glutamate required for memory and learning. OBJECTIVES:
      To determine the clinical efficacy and safety of memantine for people with
      Alzheimer's disease, or vascular or mixed dementia. SEARCH STRATEGY: Trials were
      identified from a search of the Trial-based Specialized Register of the Cochrane
      Dementia and Cognitive Improvement Group on 7 April 2004 using the terms:
      memantin*, namenda*, ebixa*, axura*, D-145, DMAA, DRG-0267. All major health care
      databases and many ongoing trial databases are searched regularly to keep this
      Register up to date. SELECTION CRITERIA: Double-blind, parallel group, placebo
      controlled, randomised and unconfounded trials in which memantine was
      administered to people with dementia. DATA COLLECTION AND ANALYSIS: Data were
      extracted, pooled where possible, and weighted mean differences, standardized
      mean differences or odds ratios were estimated. Intention-to-treat (ITT) and
      observed cases (OC) analyses are reported, where data were available. MAIN
      RESULTS: The evidence suggests that memantine has a positive effect on cognition,
      mood and behaviour and the ability to perform activities of daily living in
      patients with moderate to severe Alzheimer's disease. The results in patients
      with mild to moderate vascular dementia, suggest a beneficial effect of 20mg/day
      of memantine on cognitive function measured at 28 weeks. However, these results
      are neither supported by an effect on ability to perform activities of daily
      living nor by an effect on the clinical impression of change. This suggests that,
      in patients with mild to moderate vascular dementia, the effect on cognitive
      function is not translated into clinically detectable changes. REVIEWERS'
      CONCLUSIONS: :Memantine 20 mg/day caused a clinically noticeable reduction in
      deterioration over 28 weeks in patients with moderate to severe Alzheimer
      disease. This was supported by less functional and cognitive deterioration.
      Patients taking memantine were less likely to become agitated. The effect in mild
      to moderate AD is unknown. Patients with mild to moderate vascular dementia
      receiving memantine 20 mg/day had less cognitive deterioration at 28 weeks but
      the effects were not clinically discernible. There is an early beneficial effect
      on cognition, mood, behaviour and clinical impression for memantine at 6 weeks.
      The drug is well tolerated in general and the incidence of adverse effects is
      low.

PMID- 15495045
TI  - Early versus delayed umbilical cord clamping in preterm infants.
AB  - BACKGROUND: Optimal timing for clamping of the umbilical cord at birth is
      unclear. Early clamping allows for immediate resuscitation of the newborn.
      Delaying clamping may facilitate transfusion of blood between the placenta and
      the baby. OBJECTIVES: To delineate the short- and long-term effects for infants
      born at less than 37 completed weeks' gestation, and their mothers, of early
      compared to delayed clamping of the umbilical cord at birth. SEARCH STRATEGY: We
      searched the Cochrane Pregnancy and Childbirth Group trials register (2 February
      2004), the Cochrane Neonatal Group trials register (2 February 2004), the
      Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1,
      2004), PubMed (1966 to 2 February 2004) and EMBASE (1974 to 2 February 2004).
      SELECTION CRITERIA: Randomized controlled trials comparing early with delayed (30
      seconds or more) clamping of the umbilical cord for infants born before 37
      completed weeks' gestation. DATA COLLECTION AND ANALYSIS: Three reviewers
      assessed eligibility and trial quality. MAIN RESULTS: Seven studies (297 infants)
      were eligible for inclusion. The maximum delay in cord clamping was 120 seconds.
      Delayed cord clamping was associated with a higher hematocrit four hours after
      birth (four trials, 134 infants; weighted mean difference 5.31, 95% confidence
      interval (CI) 3.42 to 7.19), fewer transfusions for anaemia (three trials, 111
      infants; relative risk (RR) 2.01, 95% CI 1.24 to 3.27) or low blood pressure (two
      trials, 58 infants; RR 2.58, 95% CI 1.17 to 5.67) and less intraventricular
      haemorrhage (five trials, 225 infants; RR 1.74, 95% CI 1.08 to 2.81) than early
      clamping. REVIEWERS' CONCLUSIONS: Delaying cord clamping by 30 to 120 seconds,
      rather than early clamping, seems to be associated with less need for transfusion
      and less intraventricular haemorrhage. There are no clear differences in other
      outcomes.

PMID- 15495046
TI  - Cytotoxic drugs and interferons for chronic inflammatory demyelinating
      polyradiculoneuropathy.
AB  - BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy is a
      disease causing progressive or relapsing and remitting weakness and numbness. It
      is probably due to an autoimmune inflammatory process. Immunosuppressive or
      immunomodulatory drugs would be expected to be beneficial. OBJECTIVES: We aimed
      to review systematically the evidence from randomised trials concerning cytotoxic
      drugs and interferons for chronic inflammatory demyelinating
      polyradiculoneuropathy. SEARCH STRATEGY: We searched the Cochrane Neuromuscular
      Disease Group trials register (searched May 2004), MEDLINE (searched January 1977
      to May 2004), EMBASE (January 1980 to May 2004), CINAHL (searched January 1982 to
      December 2001) and LILACS (searched January 1982 to December 2001). We contacted
      the authors of the trials identified and other disease experts seeking other
      published and unpublished trials. SELECTION CRITERIA: We sought randomised and
      quasi-randomised trials of all immunosuppressive agents such as azathioprine,
      cyclophosphamide, methotrexate, cyclosporin A, mycophenolate mofetil, and
      rituximab and all immunomodulatory agents such as alpha interferon and beta
      interferon in participants fulfilling standard diagnostic criteria for chronic
      inflammatory demyelinating polyradiculoneuropathy. DATA COLLECTION AND ANALYSIS:
      Two of us independently selected the trials which met our criteria, judged their
      methodological quality and extracted the data onto specially designed forms. We
      wanted to measure the change in disability after one year as our primary outcome
      measure. MAIN RESULTS: We found one parallel group open trial of azathioprine for
      nine months involving 27 participants and another of interferon beta involving 10
      participants in a double blind crossover trial with each treatment period lasting
      12 weeks. Neither trial provided our primary outcome measure and neither showed a
      significant beneficial effect on any of the outcome measures selected by the
      authors or ourselves in the protocol for this review. REVIEWERS' CONCLUSIONS: The
      evidence is inadequate to decide whether azathioprine, interferon beta or any
      other immunosuppressive drug or interferon is beneficial in chronic inflammatory
      demyelinating polyradiculoneuropathy.

PMID- 15495047
TI  - Short acting insulin analogues versus regular human insulin in patients with
      diabetes mellitus.
AB  - BACKGROUND: In short acting insulin analogues the dissociation of hexamers is
      facilitated, achieving peak plasma concentrations about twice as high and within
      approximately half the time compared to regular human insulin. According to these
      properties this profile resembles the shape of non-diabetic patients more than
      that of regular human insulins. Despite this theoretical superiority of short
      acting insulin analogues over regular human insulin, the risk-benefit ratio of
      short acting insulin analogues in the treatment of diabetic patients is still
      unclear. OBJECTIVES: To assess the effect of treatment with short acting insulin
      analogues versus regular human insulin. SEARCH STRATEGY: A highly sensitive
      search for randomised controlled trials combined with key terms for identifying
      studies on short acting insulin analogues versus regular human insulin was
      performed using the Cochrane Library (issue 4, 2003), MEDLINE and EMBASE. Date of
      last search was December 2003. SELECTION CRITERIA: We included randomised
      controlled trials with diabetic patients of all ages that compared short acting
      insulin analogues to regular human insulin. Intervention duration had to be at
      least 4 weeks. DATA COLLECTION AND ANALYSIS: Trial selection as well as
      evaluation of study quality was done by two independent reviewers. The quality of
      reporting of each trial was assessed according to a modification of the quality
      criteria as specified by Schulz and Jadad. MAIN RESULTS: Altogether 7933
      participants took part in 42 randomised controlled studies. Most studies were of
      poor methodological quality. In patients with type 1 diabetes, the weighted mean
      difference (WMD) of HbA1c was estimated to be -0.1% (95% CI: -0.2% to -0.1%) in
      favour of insulin analogue, whereas in patients with type 2 diabetes the WMD was
      estimated to be 0.0% (95% CI: -0.1% to 0.1%). In subgroup analyses of different
      types of interventions in type 1 diabetic patients, the WMD in HbA1c was -0.2%
      (95% CI: -0.3% to -0.1%) in favour of insulin analogue in studies using
      continuous subcutaneous insulin injections (CSII) whereas for conventional
      intensified insulin therapy (IIT) studies the WMD in HbA1c was -0.1% (95% CI: 
      0.2% to -0.0%). The WMD of the overall mean hypoglycaemic episodes per patient
      per month was -0.2 (95% CI: -1.2 to 0.9) and -0.2 (95%CI: -0.5 to 0.1) for
      analogues in comparison to regular insulin in patients with type 1 diabetes and
      type 2 diabetes, respectively. For studies in type 1 diabetic patients the
      incidence of severe hypoglycaemia ranged from 0 to 247.3 (median 20.3) episodes
      per 100 person-years for insulin analogues and from 0 to 544 (median 37.2) for
      regular insulin, in type 2 the incidence ranged from 0 to 30.3 (median 0.6)
      episodes per 100 person-years for insulin analogues and from 0 to 50.4 (median
      2.8) for regular insulin. No study was designed to investigate possible long term
      effects (e.g. mortality, diabetic complications), in particular in patients with
      diabetes related complications. REVIEWERS' CONCLUSIONS: Our analysis suggests
      only a minor benefit of short acting insulin analogues in the majority of
      diabetic patients treated with insulin. Until long term efficacy and safety data
      are available we suggest a cautious response to the vigorous promotion of insulin
      analogues. Due to fears of potentially carcinogenic and proliferative effects,
      most studies to date have excluded patients with advanced diabetic complications.
      For safety purposes, we need a long-term follow-up of large numbers of patients
      who use short acting insulin analogues. Furthermore, we need well designed
      studies in pregnant women to determine the safety profile for both the mother and
      the unborn child.

PMID- 15495048
TI  - Pharmacological interventions for treating acute heterotopic ossification.
AB  - BACKGROUND: Heterotopic ossification (HO) is the formation of mature lamellar
      bone in soft tissue sites outside the skeleton. HO frequently complicates burns,
      arthroplasty, fractures, and spinal cord and brain injuries. It can impair joint
      function. OBJECTIVES: To determine the efficacy of medications to treat acute HO
      on radiological, symptomatic, functional impairment, and disability outcomes.
      SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group
      specialised register, the Cochrane Central Register of Controlled Trials (The
      Cochrane Library, Issue 2, 2004), MEDLINE (1966 to August 2004), EMBASE (1980 to
      August 2004), CINAHL (1982 to August 2004), other databases, reference lists of
      articles, and contacted trialists and drug companies. No language restrictions
      were applied. SELECTION CRITERIA: All randomised or quasi-randomised controlled
      trials that assessed the efficacy of any medication for treating acute HO
      (confirmed by bone scintigraphy, radiography, ultrasonography, or biopsy) and
      which used radiography to grade post-treatment HO severity. DATA COLLECTION AND
      ANALYSIS: Two reviewers independently assessed the study quality and extracted
      data. We analysed two dichotomous outcomes: no progression in HO grade (versus
      progression) and improvement in HO grade (versus no improvement). MAIN RESULTS:
      Two randomised trials comparing disodium etidronate versus placebo were included
      (Ono 1988; Stover 1976), from which ninety-two participants with spinal cord
      injury had radiographically-proven HO at baseline. At the completion of the 12
      week intervention, the Ono study but not the Stover study, suggested that
      disodium etidronate was associated with a significantly greater likelihood of
      successfully preventing the progression of radiographic HO grade, (relative risk
      (RR) 1.50; 95% confidence interval (CI) I 1.16 to 1.93; and RR 1.48; 95% CI 0.78
      to 2.84 respectively) and a significantly greater likelihood of improvement in HO
      grade (RR 2.78; 95% CI 1.66 to 4.66; and RR 0.71; 95% CI 0.20 to 2.53
      respectively). There was evidence of statistical heterogeneity for the latter
      outcome. Longer term radiographic, clinical or side effect outcomes were
      unavailable. Data was not pooled due to this heterogeneity and the inadequate
      duration of follow up. REVIEWERS' CONCLUSIONS: Given the absence of long term
      radiographic outcomes in the included studies, there is insufficient evidence to
      recommend the use of disodium etidronate or other pharmacological agents for the
      treatment of acute HO. It has been previously suggested that disodium etidronate
      acts by delaying, rather than preventing, the mineralization of HO, and that
      mineralization may occur after treatment cessation in many cases, thereby
      negating the benefit of disodium etidronate on eventual HO grade. Further studies
      are required to assess all pharmacological treatments for acute HO with
      sufficient follow-up duration.

PMID- 15495049
TI  - Antitumour antibiotic containing regimens for metastatic breast cancer.
AB  - BACKGROUND: Antitumour antibiotics are used in the management of metastatic
      breast cancer. Some of these agents have demonstrated higher tumour response
      rates than non-antitumour antibiotic regimens, however a survival benefit has not
      been established in this setting. OBJECTIVES: To identify and review the
      randomised evidence comparing anti-tumour antibiotic containing chemotherapy
      regimens with regimens not containing an anti-tumour antibiotic 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" and "chemotherapy".
      Details of the search strategy and coding applied by the Group to create the
      register are described in the Group's module on The Cochrane Library. SELECTION
      CRITERIA: Randomised trials comparing anti-tumour antibiotic containing regimens
      with regimens not containing anti-tumour antibiotics 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 (HRs) were derived from
      time-to-event outcomes where possible, and a fixed effect model was used for meta
      analysis. Response rates were analysed as dichotomous variables. Quality of life
      and toxicity data were extracted where present. A primary analysis was conducted
      for all trials and by class of antitumour antibiotic. MAIN RESULTS: Thirty-three
      trials reporting on 45 treatment comparisons were identified. All trials
      published results for tumour response and 26 trials published time-to-event data
      for overall survival. The observed 4084 deaths in 5284 randomised women did not
      demonstrate a statistically significant difference in survival between regimens
      that contained antitumour antibiotics and those that did not (HR 0.97, 95% CI
      0.91 to 1.03, P = 0.35) and no significant heterogeneity. Antitumour antibiotic
      regimens were favourably associated with time-to-progression (HR 0.84, 95% CI
      0.77 to 0.91) and tumour response rates (odds ratio (OR) 1.34, 95% CI 1.21 to
      1.48) although statistically significant heterogeneity was observed for these
      outcomes. These associations were consistent when the analysis was restricted to
      the 29 trials that reported on anthracyclines. Patients receiving anthracycline
      containing regimens were also more likely to experience toxic events compared to
      patients receiving non-antitumour antibiotic regimens. No statistically
      significant difference was observed in any outcome between mitoxantrone
      containing and non-antitumour antibiotic-containing regimens. REVIEWERS'
      CONCLUSIONS: Compared to regimens without antitumour antibiotics, regimens that
      contained these agents showed a statistically significant advantage for tumour
      response and time to progression in women with metastatic breast cancer but were
      not associated with an improvement in overall survival. The favourable effect on
      tumour response and time to progression observed in anthracycline-containing
      regimens was also associated with greater toxicity.

PMID- 15495050
TI  - Strategies for managing sexual dysfunction induced by antidepressant medication.
AB  - BACKGROUND: Sexual dysfunction (including altered desire, orgasmic dysfunction,
      erectile and ejaculatory problems) is a relatively common side effect of
      antidepressant medication. These sexual side effects may compromise a person's
      lifestyle and result in a lack of compliance with the prescribed antidepressant
      to the detriment of the person's mental health. OBJECTIVES: The objective of this
      review was to assess the effectiveness of management strategies for sexual
      dysfunction caused by antidepressant medication. SEARCH STRATEGY: We searched the
      CCDANCTR (March 2003), the Cochrane Central Register of Controlled Trials
      (Cochrane Library issue 2, 2004), MEDLINE (1966 - June 2004), EMBASE (1980 -
      March 2004), CINAHL (1982 - March 2004), PsycINFO (1984 - March 2004) and the
      reference lists of articles. We also contacted pharmaceutical companies and
      experts in the field of sexology. SELECTION CRITERIA: Randomised controlled
      trials comparing the management strategies for antidepressant induced sexual
      dysfunction were included. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently extracted data and assessed trial quality. Study authors were
      contacted for additional information. Adverse effect information was collected
      from the trials. MAIN RESULTS: Fifteen trials involving 904 people were included.
      One trial involving 75 people with sexual dysfunction due to sertraline assessed
      changing antidepressant. Switching to nefazodone was significantly less likely to
      result in the re-emergence of sexual dysfunction than restarting sertraline (RR
      0.34, 95% CI 0.15 - 0.6) and was not associated with any worsening of depression.
      Fourteen trials involving 829 people assessed the addition of other medication
      while continuing the same antidepressant. Meta-analysis of two trials involving
      113 men with erectile dysfunction found that the addition of sildenafil resulted
      in less sexual dysfunction at endpoint on rating scales including the
      International Index of Erectile Function (IIEF; WMD 19.36, 95% CI 15.00 to
      23.72). There was no significant difference in dropout rates between sildenafil
      and placebo. One trial found the addition of bupropion led to improved scores on
      the Changes in Sexual Functioning Questionnaire desire-frequency subscale (WMD
      0.88, 95% CI 0.21 - 1.55). One trial found that the addition of tadalafil was
      associated with greater improvement in the erectile function domain of the IIEF
      than placebo (WMD 8.10; 95% CI 4.62 to 11.68). Other augmentation strategies
      failed to show statistically significant improvements in sexual dysfunction
      compared with placebo. REVIEWERS' CONCLUSIONS: The currently available evidence
      is rather limited, with small numbers of trials assessing each strategy. However,
      while further randomised data is awaited, for men with antidepressant-induced
      erectile dysfunction, the addition of sildenafil appears to be an effective
      strategy.

PMID- 15495051
TI  - Behavioural and cognitive-behavioural interventions for outwardly-directed
      aggressive behaviour in people with learning disabilities.
AB  - BACKGROUND: Outwardly directed aggressive behaviour is a significant part of
      problem behaviours presented by people with learning disabilities. Prevalence
      rates between 3.3% to 36% have been reported in the literature. Such behaviours
      run a long term course and are a major cause of social exclusion OBJECTIVES: To
      determine the efficacy of behavioural and cognitive behavioural interventions for
      outwardly-directed aggressive behaviour for people with learning disabilities.
      SEARCH STRATEGY: The Cochrane Library (CENTRAL), MEDLINE, EMBASE, CINAHL, ERIC
      and PsycINFO were searched using a strategy combining (Learning or synonyms) and
      (Disabilities or synonyms) and (Behaviour or synonyms) and (treatment or
      synonyms) to late 2002. Where appropriate, research filters were used. SELECTION
      CRITERIA: Studies were selected if more than 4 participants, children or adults,
      were allocated by random or quasi-random methods to either intervention or
      standard treatment/wait list. DATA COLLECTION AND ANALYSIS: References identified
      by electronic searches, examinations of bibliography and personal contacts were
      screened against inclusion criteria by two independent reviewers. MAIN RESULTS:
      Three studies based on adult populations with learning disabilities were deemed
      to be suitable for inclusion but data were only available in a form suitable for
      meta-analysis in two studies. Direct interventions based on cognitive-behavioural
      methods (modified relaxation, assertiveness training with problem solving, and
      anger management) appear to have some impact on reduction of aggressive behaviour
      at the end of treatment but not at follow up (up to six months) as rated by
      individuals and their carers. REVIEWERS' CONCLUSIONS: The existing evidence on
      the efficacy of cognitive behavioural and behavioural interventions on outwards
      directed aggression in children and adults with ID is scant. There is a paucity
      of methodologically sound clinical trials. Given the impact of such behaviours on
      the affected individual, his or her carers and on service providers, effective
      interventions are essential. It is also important to investigate cost efficacy of
      treatment models against existing treatments. We recommend that randomised
      controlled trials of sufficient power are carried out using primary outcomes of
      reduction in outward directed aggression, improvement in quality of life and cost
      efficacy as measured by standardised scales.

PMID- 15495044
TI  - Omega 3 fatty acids for prevention and treatment of cardiovascular disease.
AB  - BACKGROUND: It has been suggested that omega 3 (W3, n-3 or omega-3) fats from
      oily fish and plants are beneficial to health. OBJECTIVES: To assess whether
      dietary or supplemental omega 3 fatty acids alter total mortality, cardiovascular
      events or cancers using both RCT and cohort studies. SEARCH STRATEGY: Five
      databases including CENTRAL, MEDLINE and EMBASE were searched to February 2002.
      No language restrictions were applied. Bibliographies were checked and authors
      contacted. SELECTION CRITERIA: RCTs were included where omega 3 intake or advice
      was randomly allocated and unconfounded, and study duration was at least six
      months. Cohorts were included where a cohort was followed up for at least six
      months and omega 3 intake estimated. DATA COLLECTION AND ANALYSIS: Studies were
      assessed for inclusion, data extracted and quality assessed independently in
      duplicate. Random effects meta-analysis was performed separately for RCT and
      cohort data. MAIN RESULTS: Forty eight randomised controlled trials (36,913
      participants) and 41 cohort analyses were included. Pooled trial results did not
      show a reduction in the risk of total mortality or combined cardiovascular events
      in those taking additional omega 3 fats (with significant statistical
      heterogeneity). Sensitivity analysis, retaining only studies at low risk of bias,
      reduced heterogeneity and again suggested no significant effect of omega 3 fats.
      Restricting analysis to trials increasing fish-based omega 3 fats, or those
      increasing short chain omega 3s, did not suggest significant effects on mortality
      or cardiovascular events in either group. Subgroup analysis by dietary advice or
      supplementation, baseline risk of CVD or omega 3 dose suggested no clear effects
      of these factors on primary outcomes. Neither RCTs nor cohorts suggested
      increased relative risk of cancers with higher omega 3 intake but estimates were
      imprecise so a clinically important effect could not be excluded. REVIEWERS'
      CONCLUSIONS: It is not clear that dietary or supplemental omega 3 fats alter
      total mortality, combined cardiovascular events or cancers in people with, or at
      high risk of, cardiovascular disease or in the general population. There is no
      evidence we should advise people to stop taking rich sources of omega 3 fats, but
      further high quality trials are needed to confirm suggestions of a protective
      effect of omega 3 fats on cardiovascular health. There is no clear evidence that
      omega 3 fats differ in effectiveness according to fish or plant sources, dietary
      or supplemental sources, dose or presence of placebo.

PMID- 15495052
TI  - Methadone at tapered doses for the management of opioid withdrawal.
AB  - BACKGROUND: Despite widespread use in many countries of tapered methadone for
      detoxification from opiate dependence, the evidence of efficacy to prevent
      relapse and promote lifestyle change has not been systematically evaluated.
      OBJECTIVES: To determine whether tapered methadone is effective to manage opioids
      withdrawal. SEARCH STRATEGY: We searched: the Cochrane Controlled Trials Register
      (Issue 1, 2000), MEDLINE (OVID 1966-2000), EMBASE (1980-2000); scan of reference
      list of relevant articles; personal communication; conference abstracts;
      unpublished trials from pharmaceutical industry; Internet (NIDA, Clinical
      Trials.org, BMJ). SELECTION CRITERIA: All randomised controlled trials focused on
      tapered methadone (length of treatment max 30 days) versus all other
      pharmacological detoxification treatments, placebo and different modalities of
      methadone detoxification programs for the treatment of opiate withdrawal. DATA
      COLLECTION AND ANALYSIS: One reviewer (LA) assessed studies for inclusion and
      undertook data extraction. Inclusion decisions and the overall process were
      confirmed by consultation between reviewers. Where possible analysis was carried
      out according to the "intention to treat" principles. MAIN RESULTS: 20 studies
      were included in the review, with 1357 participants. 10 studies compared
      methadone with adrenergic agonists, 7 studies compared different modalities of
      methadone detoxification, 2 studies compared methadone with other opioid
      agonists, 1 study with chlordiazepoxide, 1 with placebo. The conclusions of the
      10 studies that compared methadone with adrenergic agonists showed no substantial
      clinical difference of the two treatments in terms of retention in treatment,
      degree of discomfort and detoxification success rates. The conclusions of the 6
      studies that compare different methadone reduction schedules, showed that
      different types of methadone withdrawal schedule produce different responses in
      terms of withdrawal symptoms and severity of them. Regarding the studies that
      compare methadone with other opioid agonists, methadyl acetate performed
      similarly to methadone on most process and outcome measures, while methadone
      reduced severity of withdrawal and had fewer drop-outs than did propoxyphene.
      Using chlordiazepoxide vs methadone, the results suggest that the two drugs had
      similar results in terms of overall effectiveness. Comparing methadone with
      placebo more severe withdrawal and more drop outs were founded in the placebo
      group. The results indicate that tapered methadone and other medications used in
      the included studies are effective in the treatment of the heroin withdrawal
      syndrome, although symptoms experienced by subjects differed according to the
      medication used and the program adopted. It seems that regardless of which
      medication is selected for heroin detoxification, the rates of subsequent heroin
      abstinence are about equal. This suggests that the medications are similar in
      terms of overall effectiveness. Improvements were achieved when other services
      such as counseling and other supporting services were offered contemporaneously
      with detoxification. REVIEWERS' CONCLUSIONS: Data from literature are hardly
      comparable; programs vary widely with regard to duration, design and treatment
      objectives, impairing the application of meta-analysis. Results of many outcomes
      could not be summarised because they were presented either in graphical form or
      provided only statistical tests and p-values. For most studies standard deviation
      for continuous variables were not provided. The studies included in this review
      confirm that slow tapering with temporary substitution of long acting opioids,
      accompanied by medical supervision and ancillary medications can reduce
      withdrawal severity. Nevertheless the majority of patients relapsed to heroin
      use. However this cannot be considered a goal for a detoxification as heroin
      dependence is a chronic, relapsing disorder and the goal of detoxification should
      be to remove or reduce dependence on heroin in a controlled and human fashion and
      not a treatment for heroin dependence.

PMID- 15495053
TI  - Number of embryos for transfer following in-vitro fertilisation or intra
      cytoplasmic sperm injection.
AB  - BACKGROUND: The traditional reliance on the transfer of multiple embryos during
      in vitro fertilisation (IVF) in order to maximise the chance of pregnancy, has
      resulted in increasing rates of multiple pregnancies. Women undergoing IVF had a
      20 - fold increased risk of twins and 400 - fold increased risk of higher order
      pregnancies (Martin 1998). The maternal and perinatal morbidity and mortality as
      well as national health service costs associated with multiple pregnancies is
      significantly high in comparison with singleton births (Luke 1992; Callahan 1994;
      Goldfarb 1996). Single embryo transfer is now being considered as an effective
      means of reducing this iatrogenic complication. This systematic review evaluates
      the effectiveness of elective two embryo transfer in comparison with single and
      more than two embryo transfer following IVF and ICSI (intra cytoplasmic sperm
      injection) treatment. OBJECTIVES: The aim of this review is to determine, whether
      in couples who undergo IVF/ICSI: (1) the elective transfer of two embryos
      improves the probability of livebirth compared with: (a) Single embryo transfer,
      (b) Three embryo transfer or (c) Four embryo transfer.(2) the elective transfer
      of three embryos improves the probability of livebirth compared with: (a) Single
      embryo transfer, or (b) Four embryo transfer, SEARCH STRATEGY: We searched the
      Cochrane Menstrual Disorders and Subfertility Group's trials register (searched
      June 2003), the Cochrane Central Register of Controlled Trials (The Cochrane
      Library, Issue 4, 2003), MEDLINE (1970 to 2003), EMBASE (1985 to 2003) 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. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently assessed eligibility and quality of trials. MAIN RESULTS: We found
      no studies that compared a policy of transferring multiple embryos on one cycle
      versus a policy of cryo- preservation and transfer of a single embryo over
      multiple cycles. We also found no trials comparing transfer of two versus three
      embryos. Three small, poorly reported trials compared transfer of two versus one
      embryo in a single cycle, and one small, poorly reported trial compared transfer
      of two versus four embryos in a single cycle. The clinical pregnancy rate per
      woman/couple associated with two embryo transfer was significantly higher
      compared to single embryo transfer (OR 2.08, 95% CI 1.24 to 3.50; test for
      overall effect p = 0.006). The live birth rate per woman/couple associated with
      two embryo transfer was also significantly higher than that associated with
      single embryo transfer (OR 1.90, 95% CI 1.12 to 3.22, test for overall effect
      p=0.02). The multiple pregnancy rate was significantly lower in women who had
      single embryo transfer (OR 9.97, 95% CI 2.61 to 38.19; p = 0.0008). The
      effectiveness of double embryo transfer versus four embryo transfer was tested in
      a single trial. There was no statistically significant differences in the
      clinical pregnancy rate (OR 0.75, 95% CI 0.26 to 2.16; p=0.6), and multiple
      pregnancy rates (OR 0.44. 95% CI 0.10 to 1.97; p = 0.28) between the two groups.
      The livebirth rate in the four embryo transfer group was higher compared to the
      two embryo transfer group, but the results were not statistically significant (OR
      0.35, 95% CI 0.11 to 1.05; p = 0.06). REVIEWERS' CONCLUSIONS: The results of this
      systematic review suggest that live birth and pregnancy rates following single
      embryo transfer are lower than those following double embryo transfer as are the
      chances of multiple pregnancy including twins. As such, it is unlikely that the
      conclusions are robust enough to catalyse a change in clinical practice. The
      studies included are limited by their small sample size, so that even large
      differences might be hidden. Cumulative livebirth rates are seldom reported. The
      data were inadequate to draw conclusions about single embryo transfer and first
      frozen single embryo transfer (1FZET) or subsequent single frozen embryo
      transfers. Until more evidence is available single embryo transfer may not be the
      preferred choice for all patients undergoing IVF/ICSI. Clinicians may need to
      individualise protocols for couples based on their risks of multiple pregnancy. A
      definitive pragmatic, large multi centre randomised controlled trial comparing
      single embryo versus double embryo transfer in terms of clinical and cost
      effectiveness as well as acceptability is required. The primary outcome measured
      should be cumulative livebirth per woman/couple.

PMID- 15495054
TI  - Insulin monotherapy versus combinations of insulin with oral hypoglycaemic agents
      in patients with type 2 diabetes mellitus.
AB  - BACKGROUND: It is unclear whether patients with type 2 diabetes who have poor
      glycaemic control despite maximal oral hypoglycaemic agents (OHAs) should be
      commenced on insulin as monotherapy, or insulin combined with oral hypoglycaemic
      agents (insulin-OHA combination therapy). OBJECTIVES: To assess the effects of
      insulin monotherapy versus insulin-OHA combinations therapy. SEARCH STRATEGY:
      Eligible studies were identified by searching MEDLINE, EMBASE, and The Cochrane
      Library. Date of last search: May 2004. SELECTION CRITERIA: Randomised controlled
      trials (RCTs) with 2 months minimum follow-up duration comparing insulin
      monotherapy (all schemes) with insulin-OHA combination therapy. DATA COLLECTION
      AND ANALYSIS: Data extraction and assessment of study quality were undertaken by
      three reviewers in pairs. MAIN RESULTS: Twenty RCTs (mean trial duration 10
      months) including 1,811 participants, with mean age 59.8 years and mean known
      duration of diabetes 9.6 years. Overall, study methodological quality was low.
      Twenty-eight comparisons in 20 RCTs were ordered according to clinical
      considerations. No studies assessed diabetes-related morbidity, mortality or
      total mortality. From 13 studies (21 comparisons), sufficient data were extracted
      to calculate pooled effects on glycaemic control. Insulin-OHA combination therapy
      had statistically significant benefits on glycaemic control over insulin
      monotherapy only when the latter was applied as a once-daily injection of NPH
      insulin. Conversely, twice-daily insulin monotherapy (NPH or mixed insulin)
      provided superior glycaemic control to insulin-OHA combination therapy regimens
      where insulin was administered as a single morning injection. In more
      conventional comparisons, regimens utilising OHAs with bedtime NPH insulin
      provided comparable glycaemic control to insulin monotherapy (administered as
      twice daily, or multiple daily injections). Overall, insulin-OHA combination
      therapy was associated with a 43% relative reduction in total daily insulin
      requirement compared to insulin monotherapy. Of the 14 studies (22 comparisons)
      reporting hypoglycaemia, 13 demonstrated no significant difference in the
      frequency of symptomatic or biochemical hypoglycaemia between insulin and
      combination therapy regimens. No significant differences in quality of life
      related issues were detected. Combination therapy with bedtime NPH insulin
      resulted in statistically significantly less weight gain compared to insulin
      monotherapy, provided metformin was used +/-sulphonylurea. In all other
      comparisons no significant differences with respect to weight gain were detected.
      REVIEWERS' CONCLUSIONS: Bedtime NPH insulin combined with oral hypoglycaemic
      agents provides comparable glycaemic control to insulin monotherapy and is
      associated with less weight gain if metformin is used.

PMID- 15495055
TI  - Botulinum toxin A as an adjunct to treatment in the management of the upper limb
      in children with spastic cerebral palsy.
AB  - BACKGROUND: Cerebral palsy (CP) is a central nervous system deficit resulting
      from a non-progressive lesion in the developing brain. Although the brain lesions
      are static, the movement disorders that arise are not unchanging and are
      characterised by atypical muscle tone, posture and movement (Rang 1990). The
      spastic motor type is the most common form of CP and its conventional therapeutic
      management may include splinting/casting, passive stretching, facilitation of
      posture and movement, spasticity-reducing medication and surgery. More recently,
      health care professionals have begun to use botulinum toxin A (BtA) as an adjunct
      to interventions in an attempt to reduce muscle tone and spasticity to improve
      function OBJECTIVES: To assess the effectiveness of intramuscular BtA injections
      as an adjunct to managing the upper limb in children with spastic CP. SEARCH
      STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The
      Cochrane Library, Issue 4, 2003), MEDLINE (1966 to March Week 3 2004), EMBASE
      (1980 to 2003 Week 16) and CINAHL (1982 to Week 3 March 2004). SELECTION
      CRITERIA: All randomised controlled trials (RCTs) comparing intramuscular BtA
      injections into any muscle group of the upper limb with placebo, no treatment or
      other interventions. DATA COLLECTION AND ANALYSIS: Two authors using standardised
      forms extracted the data independently. Each trial was assessed for internal
      validity with differences resolved by discussion. Data was extracted and entered
      into RevMan 4.2.3. MAIN RESULTS: Two trials met the inclusion criteria, each
      having short-term follow up, a small number of subjects and using a single set of
      injections. The study by Corry 1997 compared BtA with an injection of normal
      saline and found promising results in elbow extension, elbow and wrist muscle
      tone. At three months, encouraging results for wrist muscle tone and grasp and
      release were noted. The trial reported median change, range of changes and the
      difference in these measures between groups. The study by Fehlings 2000 compared
      BtA with no intervention. When data were analysed no treatment effect was found
      for quality of upper limb function, passive range of motion, muscle tone, grip
      strength or self-care ability. REVIEWERS' CONCLUSIONS: This systematic review has
      not found sufficient evidence to support or refute the use of intramuscular
      injections of BtA as an adjunct to managing the upper limb in children with
      spastic cerebral palsy. Only one of the two identified RCTs reported some
      promising results in support of reduced muscle tone following BtA injections.
      Further research incorporating larger sample sizes, rigorous methodology,
      measurement of upper limb function and functional outcomes is essential.

PMID- 15495056
TI  - Metoclopramide, thickened feedings, and positioning for gastro-oesophageal reflux
      in children under two years.
AB  - BACKGROUND: Gastro-esophageal reflux (GER) is the refluxing of gastric contents
      into the esophagus. Fifty per cent of all infants 0 to 3 months regurgitate at
      least once a day. This drops to 5% once infants are 10 to 12 months old. Three
      per cent of parents of 10 to 12 month old infants view this as a problem.
      OBJECTIVES: To investigate the effectiveness of thickened feeds, positioning, and
      metoclopramide as compared to placebo in improving the outcome of GER in
      developmentally normal infants aged one month to two years. SEARCH STRATEGY: We
      searched the Cochrane Central Register of Controlled Trials (The Cochrane Library
      2003), MEDLINE (January 1966 to 23 January 2003), EMBASE (January 1985 to 27
      January 2003), and reference lists of articles. SELECTION CRITERIA: Randomised
      studies (parallel or cross over) which evaluated thickened feeds, positional
      alternations or metoclopramide for the treatment of GER in children between the
      age of one month and two years who were developmentally normal. DATA COLLECTION
      AND ANALYSIS: All three reviewers independently assessed trial quality and
      extracted data. Study authors were contacted for additional information. Adverse
      effects information was collected from the trials. MAIN RESULTS: Twenty trials
      involving 771 children met the inclusion criteria: eight dealt with thickened
      feeds, five with positioning, and seven with metoclopramide. Few comparisons
      could be made, and so summary measures were often made with two or three studies.
      Thickened feeds reduce the regurgitation severity score (standardized mean
      difference (SMD) -0.94;95% confidence interval -1.35 to -0.52), as well as the
      frequency of emesis (SMD -0.91; confidence interval -1.22 to -0.61). The reflux
      index was not reduced (weighted mean difference (WMD) 0.48%; 95% confidence
      interval-3.27 to 4.23). All five positioning studies utilized esophageal pH
      monitoring as their outcome measure. Elevating the head of the crib for treating
      reflux in the supine position is not justifiable. The seven metoclopramide
      studies used a variety of outcomes. Compared to placebo, metoclopramide appears
      to reduce daily symptoms ( SMD -0.73; 95% confidence interval -1.16 to -0.30),
      and reduce the reflux index (WMD -2.80%; 95% confidence interval -5.58 to -0.01).
      It does increase side effects. REVIEWERS' CONCLUSIONS: Thickened feeds are
      helpful in reducing the symptoms of GER. Elevating the head of the crib in the
      supine position does not have any effect. Metoclopramide may have some benefit in
      comparison to placebo in the symptomatic treatment for GER, but that must be
      weighed against possible side effects. .

PMID- 15495057
TI  - Interventions to improve compliance with continuous positive airway pressure for
      obstructive sleep apnoea.
AB  - BACKGROUND: Continuous Positive Airways Pressure (CPAP) is currently considered
      to be the cornerstone of therapy for sleep apnoea (OSA). However compliance with
      this treatment is frequently poor, which may lead to ongoing symptoms of sleep
      disruption, daytime sleepiness and poor waking cognitive function. Mechanical and
      psychological/educational interventions have been proposed to try to increase the
      hours of use of CPAP therapy. OBJECTIVES: To determine the efficacy of
      interventions designed to increase compliance with CPAP. SEARCH STRATEGY: We
      searched the Cochrane Airways Group Sleep Apnoea Specialised Register (January
      2004). SELECTION CRITERIA: Randomised controlled trials (RCTs) assessing
      interventions to improve compliance with CPAP usage were considered for inclusion
      in the review. DATA COLLECTION AND ANALYSIS: Two reviewers assessed articles for
      inclusion in the review and extracted data. Attempts were made to obtain
      additional unpublished data from the trialists. MAIN RESULTS: 24 studies met the
      inclusion criteria with 1007 participants. Each of the mechanical interventions
      was compared with fixed CPAP alone. Auto-CPAP (13 studies): A small, significant
      difference was observed in compliance but this effect disappeared when we took
      account of the variation between the studies. There may be a subgroup of patients
      who respond better than others. Most participants preferred auto-CPAP to fixed
      CPAP where this was measured. Bi-level PAP (3 studies): No significant
      differences were observed in compliance. One small study found no difference in
      preference. Patient titrated CPAP (1 study): No significant difference was
      observed in compliance. Humidification(1 study): This small study found no
      significant difference in compliance. Educational/psychological interventions (6
      studies): One small study demonstrated superior compliance in patients treated
      with cognitive behavioural therapy + CPAP versus CPAP alone but only after 12
      weeks. In one, larger study intensive support including home visits increased
      hours of use. No other study demonstrated significant effects in favour of active
      treatment. REVIEWERS' CONCLUSIONS: The effect of Auto-CPAP in increasing hours of
      use in unselected patients starting this treatment remains unclear. Different
      pooled analyses gave conflicting results and it may be that carefully selected
      participants may respond more favourably than others. The evidence in support of
      Bi-PAP, self-titration and humidification is lacking and studies are required in
      these areas. There is some evidence that psychological/educational interventions
      improve CPAP usage. This requires confirmation in larger studies of longer
      duration, with rigorous follow-up. The cost-benefit ratio of such interventions
      requires assessment. Future studies need to consider the effects of treatment in
      participants who are poorly compliant. The studies assembled were characterised
      by high machine usage in the control groups, and low withdrawal rates making it
      less likely that any benefit could be demonstrated.

PMID- 15495058
TI  - Sildenafil for pulmonary hypertension.
AB  - BACKGROUND: Pulmonary Hypertension (PH) can be either of unknown aetiology
      (primary pulmonary hypertension (PPH)) or due to a known underlying cause
      (secondary pulmonary hypertension (SPH). Pulmonary arteriolar vasoconstriction is
      considered to be an important characteristic of PH. Therapies which aim to
      vasodilate are used to treat pulmonary hypertension. OBJECTIVES: To determine the
      clinical efficacy of sildenafil, a vasodilator which works through inhibition of
      the enzyme phosphodiesterase type V (PDE5I), administered via any route to people
      with pulmonary hypertension in primary or secondary forms. SEARCH STRATEGY:
      Electronic databases were searched with pre-defined search terms. Searches were
      current as of November 2003. SELECTION CRITERIA: Randomised controlled trials
      were considered for inclusion in the review. We included studies which assessed
      the effects of sildenafil in participants with PPH and SPH. DATA COLLECTION AND
      ANALYSIS: Two reviewers independently assessed and extracted data from clinical
      trials. Data were entered in RevMan Analyses 1.0.2. Continuous data were pooled
      with an estimate on either WMD (weighted mean difference) or SMD (standardised
      mean difference) scales. Dichotomous data were pooled and a RR (relative risk)
      was calculated. MAIN RESULTS: Four studies recruiting 77 participants met the
      inclusion criteria of the review. Two studies assessed the acute effects of
      sildenafil. Two small crossover study assessed the effects of long term
      administration. The 'acute effect' studies indicated that sildenafil has a
      pulmonary vasodilatory effect. The two crossover studies showed improvement in
      symptoms. One study showed improvement in fatigue domains from a validated health
      status questionnaire. Both crossover studies reported that the drug was well
      tolerated. REVIEWERS' CONCLUSIONS: The validity of the observed effects is
      undermined by small participant numbers and inadequate exploration of the
      different disease etiologies. The effects on long term outcome such as NYHA
      functional class, symptoms, mortality and exercise capacity require further
      validation. More studies of adequate size are required before the long term
      effects of sildenafil on clinically important outcomes can be established.

PMID- 15495059
TI  - Interventions for preventing post-operative atrial fibrillation in patients
      undergoing heart surgery.
AB  - BACKGROUND: Post-operative atrial fibrillation is a common complication of
      cardiac surgery and has been associated with increased incidence of other
      complications including post-operative stroke, increased hospital length of stay
      and increased cost of hospitalisation. Prevention of atrial fibrillation is a
      reasonable clinical goal and, consequently, many randomised trials have evaluated
      the effectiveness of pharmacological and non-pharmacological interventions. We
      systematically reviewed the literature and prepared meta-analyses to better
      understand the role and effects of various prophylactic therapies against post
      operative atrial fibrillation. OBJECTIVES: To assess the effects of
      pharmacological and non-pharmacological interventions for preventing post-cardiac
      surgery atrial fibrillation. SEARCH STRATEGY: We searched CENTRAL, MEDLINE,
      EMBASE and CINAHL from earliest achievable date to June 2003. We hand searched
      references from reports and earlier reviews. We searched abstract books and CD
      ROMs from annual scientific meetings of American College of Cardiology, American
      Heart Association, North American Society of Pacing and Electrophysiology and
      European Heart Organization between 1997-2003. No language restrictions were
      applied. SELECTION CRITERIA: Randomised controlled trials comparing
      pharmacological interventions or non-pharmacological interventions with control
      treatment, placebo or usual care for the prevention of post-operative atrial
      fibrillation in post-coronary artery bypass grafting or combined CABG and
      valvular surgery. DATA COLLECTION AND ANALYSIS: Two reviewers assessed trial
      quality and extracted data. Study authors were contacted for additional
      information. MAIN RESULTS: Fifty eight studies were included with a total of 8565
      participants. Interventions included were amiodarone, beta blockers, solatol and
      pacing. Results favoured treatment for post-operative atrial fibrillation. The
      data for stroke favoured treatment by a non-significant effect size of 0.81, 95%
      confidence interval 0.51 to 1.28. Similarly, a positive indication for length of
      stay was derived but it too was not significant with a weighted mean difference
      of -0.66, 95% confidence interval -0.95 to -0.37. A positive result for cost of
      hospitalisation in favour of treatment was achieved, but the statistic is not
      significant due to low power and large standard deviations: a weighted mean
      difference of -2717, 95% confidence interval 7518 to 2084. Beta-blockers had the
      greatest magnitude of effect across 28 trials (4074 patients) with an odds ratio
      (random) of 0.35, 95% confidence interval 0.26 to 0.49. Across all treatment, the
      odds ratio favoured treatment with a ratio (random) of 0.43, 95% confidence
      interval 0.37 to 0.51. REVIEWERS' CONCLUSIONS: Intervention is favoured across
      the three pharmacological interventions studied and the one non-pharmacological
      intervention, pacing. The length of stay data favoured treatment (-0.66, 95%
      confidence interval -0.95 to -0.37).

PMID- 15495060
TI  - Endoscopic retrograde cholangiopancreatography in gallstone-associated acute
      pancreatitis.
AB  - BACKGROUND: Early endoscopic retrograde cholangio-pancreatography with or without
      endoscopic sphincterotomy (ERCP+/-ES) has been advocated to reduce complications
      in patients presenting with a severe attack of gallstone-associated acute
      pancreatitis (GAP). However, a recent trial has reported contradictory results.
      Importantly, patients with acute cholangitis were excluded suggesting it may be a
      major confounding factor affecting previous studies. OBJECTIVES: To assess the
      effectiveness of early ERCP+/-ES compared to conservative management stratified
      according to severity of disease, concealment of randomisation, acute cholangitis
      and bilirubin level in the reduction of mortality, morbidity, length of
      hospitalisation and cost in adults suspected of having GAP. SEARCH STRATEGY: We
      searched - Cochrane Library (Issue 4 2003), Medline (1966-2004), EMBASE (1980
      2004) and LILACS. 'Grey literature' was sought by looking at cited references and
      hand searched to identify further relevant trials. Conference proceedings of
      United European Gastroenterology Week (published in Gut) and Digestive Disease
      Week (published in Gastroenterology) were also hand searched. SELECTION CRITERIA:
      Randomized controlled trials (RCT) of adult patients, from 15 years old or
      greater, presenting with gallstone-associated acute pancreatitis (GAP) comparing
      ERCP +/- ES versus Conservative management within 72 hours of admission. DATA
      COLLECTION AND ANALYSIS: Data were assessed for quality independently by two
      reviewers. Wherever appropriate, results were pooled together and sub-grouped by
      predicted severity of disease. Fixed and random effects models were applied.
      Sensitivity analysis was performed to test the fragility of results. MAIN
      RESULTS: Three trials, involving 511 patients, met inclusion criteria. The test
      for heterogeneity yielded statistically non-significant results (p-value 0.1 to
      0.63) suggesting all comparisons were above the established threshold for
      combinability (p<0.1). Fixed effect and random effect meta-analyses gave
      identical results. Early ERCP +/- ES was associated with non-significant effect
      on reduction of mortality in predicted mild (OR = 0.62, 95% CI = 0.27 to 1.41)
      and severe GAP (OR = 0.62, 95% CI = 0.27 to 1.41). Reduction in complications was
      non-significant in predicted mild (OR = 0.89, 95% CI = 0.53 to 1.49), but
      significant in severe GAP (OR = 0.27, 95% CI = 0.14 to 0.53). There was
      insufficient evidence to draw any conclusions about hospital stay and cost.
      REVIEWERS' CONCLUSIONS: Odds of having complications are reduced in predicted
      severe disease by early ERCP +/- ES. This effect was however, non-significant in
      predicted mild disease and for reduction of mortality in either predicted mild or
      severe disease. These results are controlled for confounding due to associated
      acute cholangitis and are robust for clinical and statistical heterogeneity.

PMID- 15495061
TI  - Selenium supplementation for critically ill adults.
AB  - BACKGROUND: Selenium is a trace mineral essential to human health, which has an
      important role in the immune response, defence against tissue damage and thyroid
      function. Improving selenium status could help protect against overwhelming
      tissue damage and infection in critically ill adults. OBJECTIVES: This review
      assessed the effects of selenium supplementation including the selenium
      containing compound, ebselen, on adults recovering from critical illness. SEARCH
      STRATEGY: We searched CENTRAL (The Cochrane Library, Issue 2, 2003), MEDLINE,
      (1966 to July 2003), EMBASE (1980 to Week 30 2003),CAB NAR (1973 to March 2003),
      BIOSIS (1985 to July 2003), CINAHL (1982 to July 2003), HEALTHSTAR (1975 to
      September 2002), Current Controlled Trials, and reference lists. We contacted
      investigators, and handsearched four journals. Date of the most recent search:
      December 2003. SELECTION CRITERIA: Randomized trials of selenium or ebselen
      supplementation by any route, in adults with critical illness (including burns,
      head injury, brain haemorrhage, cerebrovascular accident and surgery). DATA
      COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed
      trial quality. We sought additional information as required from trialists. We
      also undertook pooling of data for outcomes and selected exploratory analyses
      were undertaken. MAIN RESULTS: Seven randomized trials involving813participants
      were included. The quality of trials, as reported, was poor, particularly for
      allocation concealment. The availability of outcome data was limited and trials
      involving selenium supplementation, were small. Thus the results must be
      interpreted with caution. Because of heterogeneity, results are presented for the
      random effects models. Four selenium trials showed no statistically significant
      difference in mortality (relative risk (RR) 0.52, 95% confidence interval (CI)
      0.20 to 1.34). Three trials of ebselen also showed no statistically significant
      difference in mortality (RR 0.83, 95% CI 0.51 to 1.35). One trial of selenium
      found no statistically significant difference between groups for participants
      developing infection (RR 1.33, 95% CI 0.55 to 3.24). Three trials of ebselen
      provided data for participants developing infections (pyrexia, respiratory
      infections or meningitis), which was not statistically significant (RR 0.60, 95%
      CI 0.36 to 1.02). No clear evidence emerged for the benefits of selenium or
      ebselen supplementation for the outcomes of days on a ventilator, length of
      intensive care unit stay, length of hospital stay or quality of life. REVIEWERS'
      CONCLUSIONS: There is insufficient evidence to recommend supplementation of
      critically ill patients with selenium or ebselen. Trials are required which
      overcome the defects of the reviewed studies, particularly inadequate size and
      methodology. This review will be updated when four ongoing trials are completed.

PMID- 15495062
TI  - Partial liquid ventilation for preventing death and morbidity in adults with
      acute lung injury and acute respiratory distress syndrome.
AB  - BACKGROUND: Acute lung injury (ALI), and acute respiratory distress syndrome
      (ARDS), are syndromes of severe respiratory failure. Adults with ALI or ARDS have
      high mortality and significant morbidity. Partial liquid ventilation (PLV) may be
      better (i.e., cause less lung damage) for these patients than other forms of
      respiratory support. Uncontrolled studies in adults have shown improvement in gas
      exchange and lung compliance with partial liquid ventilation. OBJECTIVES: To
      assess whether partial liquid ventilation reduces morbidity and mortality in
      adults with ALI or ARDS. SEARCH STRATEGY: We searched The Cochrane Central
      Register of Controlled Trials (CENTRAL), The Cochrane Library Issue 2, 2004;
      MEDLINE (1966 to May 2004); and CINAHL (1982 to May 2004); intensive care
      journals and conference proceedings; reference lists and unpublished literature.
      SELECTION CRITERIA: Randomized controlled trials which compared partial liquid
      ventilation with other forms of ventilation, in adults (16 years old or greater)
      with ALI or ARDS, reporting one or more of the following: mortality; duration of
      mechanical ventilation, respiratory support, oxygen therapy, stay in the
      intensive care unit, or stay in hospital; infection; long term cognitive
      impairment or health related quality of life; long term lung function; or cost.
      DATA COLLECTION AND ANALYSIS: Two reviewers independently evaluated the quality
      of the relevant studies and extracted the data from the included studies. MAIN
      RESULTS: Problems with the inadequacy of the primary report of the one included
      study do not allow us to report any quantitative results for patients with ALI or
      ARDS. The only outcome we considered to be of clinical significance and reported
      for all enrolled patients (i.e., patients with ALI and ARDS and less severe
      respiratory insufficiency) was 28 day mortality. There was no statistically
      significant difference between groups for this outcome with a relative risk for
      28 day mortality in the PLV group of 1.15 (95% confidence intervals of 0.64 to
      2.10). REVIEWERS' CONCLUSIONS: There is no evidence from randomized controlled
      trials to support or refute the use of partial liquid ventilation in adults with
      ALI or ARDS; adequately powered, high quality randomized controlled trials are
      still needed to assess its efficacy. Clinically relevant outcome measures should
      be assessed (especially mortality at discharge and later, duration of respiratory
      support and hospital stay, and long term cognitive and quality of life outcomes)
      and the studies should be published in full.

PMID- 15495063
TI  - Reduced osmolarity oral rehydration solution for treating cholera.
AB  - BACKGROUND: Oral rehydration solution (ORS) is used to treat dehydration caused
      by diarrheal diseases including cholera. Reduced osmolarity formulations are safe
      and more effective than standard ORS for treating non-cholera diarrhea. As
      cholera causes rapid electrolyte loss, it is important to know if these benefits
      are similar for people with cholera. OBJECTIVES: To compare the safety and
      efficacy of reduced osmolarity oral rehydration solution (ORS) with standard ORS
      for treating diarrhea due to cholera. SEARCH STRATEGY: We searched the Cochrane
      Infectious Disease Group Specialized Register (January 2004), CENTRAL (The
      Cochrane Library Issue 1, 2004), MEDLINE (1966 to January 2004), EMBASE (1974 to
      January 2004), and LILACS (1982 to January 2004). We also contacted organizations
      and searched reference lists. SELECTION CRITERIA: Randomized controlled trials
      comparing reduced osmolarity ORS with standard ORS for treating adults and
      children with acute diarrhea due to cholera. DATA COLLECTION AND ANALYSIS: Two
      reviewers independently applied eligibility criteria, assessed trial quality, and
      extracted data. We pooled binary data using relative risks (RR), continuous data
      using weighted mean difference (WMD) or the standardized mean difference (SMD),
      and presented the results with 95% confidence intervals (CI). MAIN RESULTS: For
      glucose-based reduced osmolarity ORS, seven trials (718 participants) met the
      inclusion criteria. Biochemical hyponatremia (serum sodium < 130 mmol/L) was more
      common with reduced osmolarity ORS (RR 1.67, CI 1.09 to 2.57; 465 participants, 4
      trials); for severe biochemical hyponatremia (serum sodium < 125 mmol/L) this was
      not significant (RR 1.58, CI 0.62 to 4.04; 465 participants, 4 trials). No trials
      reported symptomatic hyponatremia or death. We found no statistically significant
      difference in the need for unscheduled intravenous infusion. Analyses separating
      children and adults showed no obvious trends. Two trials also examined rice-based
      ORS. In the reduced osmolarity group, duration of diarrhea was shorter (WMD 
      16.85 hours, CI -21.22 to -12.48; 102 participants, 2 trials). REVIEWERS'
      CONCLUSIONS: In people with cholera, reduced osmolarity ORS is associated with
      biochemical hyponatremia when compared with standard ORS, although there are
      similar benefits in terms of other outcomes. Although this risk does not appear
      to be accompanied by serious consequences, the total patient experience in
      existing trials is small. Under wider practice conditions, especially where
      patient monitoring is difficult, caution is warranted.

PMID- 15495064
TI  - Antibiotic prophylaxis for hernia repair.
AB  - BACKGROUND: The use of antibiotic prophylaxis for hernia repair is currently a
      controversial issue given the disparity among study results in this area.
      OBJECTIVES: The objective of this systematic review was to clarify the
      effectiveness of antibiotic prophylaxis in reducing postoperative wound infection
      rates in elective open inguinal hernia repair. SEARCH STRATEGY: Searches in the
      Cochrane Colorectal Cancer Group specialized register were conducted crossing the
      terms herni* and inguinal or groin and the terms antimicr* or antibiot* , as free
      text and MeSH terms. A similar search in Medline (WebSPIRS from Silver Platter,
      January/1966 to March/2004) and Embase (1976 to December/2003) was conducted
      using the following terms: #1 antibiotic* or antimicrob* or anti infecti* or
      antiinfecti*; #2 prophyla* or prevent*; #3 #1 and #2; #4 clean and (surgery or
      tech* or proced*); #5 herni*; #6 (wound infection) and #4; #7 #3 and (#4 or #5 or
      #6). Reference lists of the included studies were checked to identify additional
      studies. SELECTION CRITERIA: Only randomized clinical trials were included. DATA
      COLLECTION AND ANALYSIS: Eight randomized clinical trials were identified. Three
      of them used prosthetic material for hernia repair (hernioplasty) whereas the
      remaining studies did not (herniorraphy). Pooled and subgroup analysis were
      conducted depending on whether prosthetic material was or not used. A random
      effects model was used in the analysis. MAIN RESULTS: The total number of
      patients included was 2907 (treatment group: 1421, control group: 1486). Overall
      infection rates were 2.88% and 4.3% in the prophylaxis and control groups,
      respectively (OR 0.65, 95%CI 0.35 - 1.21). The subgroup of patients with
      herniorrhaphy had infection rates of 3.78% and 4.87% in the prophylaxis and
      control groups, respectively (OR 0.84, 95%CI 0.53 - 1.34). The subgroup of
      patients with hernioplasty had infection rates of 1.2% and 3,3% in the
      prophylaxis and control groups, respectively (OR 0.28, 95%CI 0.02 - 3.14).
      REVIEWERS' CONCLUSIONS: Based on the results of this meta-analysis, there was no
      clear evidence that routine administration of antibiotic prophylaxis for elective
      inguinal hernia repair reduced infection rates.

PMID- 15495065
TI  - Interventions for preventing oral candidiasis for patients with cancer receiving
      treatment.
AB  - BACKGROUND: Treatment of cancer is increasingly more effective but is associated
      with short and long term side effects. Oral side effects remain a major source of
      illness despite the use of a variety of agents to prevent and treat them. One of
      these side effects is oral candidiasis. OBJECTIVES: To assess the effectiveness
      of interventions (which may include placebo or no treatment) for the prevention
      of oral candidiasis for patients with cancer receiving chemotherapy and/or
      radiotherapy. SEARCH STRATEGY: Electronic databases: Cochrane Oral Health Group's
      Trials Register, CENTRAL, MEDLINE, MEDLINE Pre-indexed, EMBASE, CINAHL,
      CANCERLIT, SIGLE and LILACS were searched. Date of the most recent searches April
      2004 (CENTRAL Issue 2, 2004). SELECTION CRITERIA: Trials were selected if they
      met the following criteria: design - random allocation of participants;
      participants - anyone receiving chemotherapy or radiotherapy treatment for
      cancer; interventions - agents prescribed to prevent oral candidiasis; primary
      outcome - prevention of oral candidiasis. DATA COLLECTION AND ANALYSIS: Data were
      recorded on the following secondary outcomes if present: relief of pain, amount
      of analgesia, relief of dysphagia, incidence of systemic infection, duration of
      stay in hospital (days), cost of oral care, patient quality of life, death, use
      of empirical antifungal treatment, toxicity and compliance. Information regarding
      methods, participants, interventions, outcome measures and results were
      independently extracted, in duplicate, by two reviewers (HW & JC). The Cochrane
      Oral Health Group statistical guidelines were followed and relative risk values
      calculated using random effects models. Potential sources of heterogeneity were
      examined in random effects metaregression analyses. MAIN RESULTS: Twenty-eight
      trials involving 4226 patients satisfied the inclusion criteria. Drugs absorbed
      and partially absorbed from the gastrointestinal (GI) tract were found to prevent
      oral candidiasis when compared to a placebo, or a no treatment control group,
      with RR for absorbed drugs = 0.47 (95% CI 0.29 to 0.78). For absorbed drugs in
      populations with an incidence of 20% (mid range of results in control groups),
      this implies a NNT of 9 (95% CI 7 to 13) patients need to be treated to avoid one
      patient getting oral candidiasis. There was no significant benefit shown for
      drugs not absorbed from the GI tract. REVIEWERS' CONCLUSIONS: There is strong
      evidence, from randomised controlled trials, that drugs absorbed or partially
      absorbed from the GI tract prevent oral candidiasis in patients receiving
      treatment for cancer. There is also evidence that these drugs are significantly
      better at preventing oral candidiasis than drugs not absorbed from the GI.

PMID- 15495066
TI  - Eradication therapy for peptic ulcer disease in Helicobacter pylori positive
      patients.
AB  - BACKGROUND: Peptic ulcer disease is the cause for dyspepsia in about 10% of
      patients. 95% of duodenal and 70% of gastric ulcers are associated with
      Helicobacter pylori. Eradication of H pylori reduces the relapse rate of ulcers
      but the magnitude of this effect is uncertain. OBJECTIVES: The primary outcomes
      were the proportion of peptic ulcers healed initially and proportion of patients
      free from relapse following successful healing. Eradication therapy was compared
      to placebo or pharmacological therapies in H. pylori positive patients. Secondary
      aims included symptom relief and adverse effects. SEARCH STRATEGY: A search was
      undertaken according to the Cochrane Upper Gastrointestinal and Pancreatic
      Diseases Review Group module using CCTR, MEDLINE, EMBASE and CINAHL databases.
      Experts in the field and pharmaceutical companies were contacted. Abstract books
      between 1994 and 2003 were hand-searched. SELECTION CRITERIA: Randomised
      controlled trials of short and long-term treatment of peptic ulcer disease in H.
      pylori positive adults were analysed. Patients received at least one week of H
      pylori eradication compared with ulcer healing drug, placebo or not treatment.
      Trials were included if they reported assessment from 2 weeks onwards. DATA
      COLLECTION AND ANALYSIS: Data were collected on ulcer healing, recurrence, relief
      of symptoms and adverse effects. MAIN RESULTS: 60 trials were eligible. Data
      extraction was not possible in 7 trials, and 53 trials were included. In duodenal
      ulcer healing, eradication therapy was superior to ulcer healing drug (UHD) (34
      trials, 3910 patients, relative risk [RR] of ulcer persisting = 0.66; 95%
      confidence interval [CI] = 0.58, 0.76) and no treatment (2 trials, 207 patients,
      RR = 0.37; 95% CI 0.26, 0.53). In gastric ulcer healing, no significant
      differences were detected between eradication therapy and UHD (13 trials, 1469
      patients, RR = 1.32; 95% CI = 0.92, 1.90). In preventing duodenal ulcer
      recurrence no significant differences were detected between eradication therapy
      and maintenance therapy with UHD (4 trials, 319 patients, relative risk [RR] of
      ulcer recurring = 0.73; 95% CI = 0.42, 1.25), but eradication therapy was
      superior to no treatment (27 trials 2509 patients, RR = 0.20; 95% CI = 0.15,
      0.26). In preventing gastric ulcer recurrence, eradication therapy was superior
      to no treatment (10 trials, 1029 patients, RR = 0.28; 95% CI 0.18, 0.43).
      REVIEWERS' CONCLUSIONS: A 1 to 2 weeks course of H. pylori eradication therapy is
      an effective treatment for H. pylori positive peptic ulcer disease.

PMID- 15495067
TI  - Replacement of estrogens and progestins to prevent morbidity and mortality in
      preterm infants.
AB  - BACKGROUND: A potential therapeutic effect of sex steroids on premature infants
      has been proposed from animal data and observational studies in humans. Purported
      benefits include reduction in chronic lung disease, improved bone density and
      improved neurodevelopmental outcome. OBJECTIVES: To determine if estrogens or
      progestins, either alone or in combination, when compared to placebo or no
      treatment, reduce morbidity and/or mortality in preterm infants. SEARCH STRATEGY:
      The standard search strategy of the Cochrane Neonatal Review Group as outlined in
      the Cochrane Library (Issue 2, 2004) was used. This included searches of the
      Oxford Database of Perinatal Trials, Cochrane Central Register of Controlled
      Trials (CENTRAL, The Cochrane Library, Issue 2, 2004), MEDLINE 1966 to July 2004
      inclusive, previous reviews including cross references, abstracts, conferences
      and symposia proceedings (Perinatal Society of Australia and New Zealand 1998
      2004 and Pediatric Academic Societies meetings 1998-2004). SELECTION CRITERIA:
      Randomised controlled trials comparing the use of estrogens and/or progestins
      with placebo or no treatment in preterm infants born less than 30 weeks gestation
      were included in this review. The primary outcome measures were neonatal
      mortality and medium-term neurodevelopmental outcome. Other outcomes included
      length of hospital stay, incidence of chronic lung disease, osteopaenia causing
      fractures and adverse effects of sex steroid administration. DATA COLLECTION AND
      ANALYSIS: Two reviewers independently selected, assessed the quality of and
      extracted data from the included studies. Meta-analyses were performed using
      relative risk and risk difference for dichotomous data, and weighted mean
      difference for continuous data with 95% confidence intervals. MAIN RESULTS: Two
      randomised controlled trials were identified by the search strategy and one was
      included in this review, comprising 30 preterm infants. There was no significant
      effect of replacement of estradiol and progesterone on the outcomes of mortality
      or neurodevelopmental disability in survivors followed. No adverse effects of sex
      steroid replacement on short or longer term outcomes were detected. REVIEWERS'
      CONCLUSIONS: The one small randomised controlled trial demonstrated neither
      evidence of benefit or harm related to the replacement of estradiol and
      progesterone in preterm infants less than 30 weeks gestation. A properly powered
      randomised controlled trial is required to determine whether or not
      administration of estradiol or progesterone, either alone or in combination, and
      at varying doses, confers any clinically significant benefits, or poses any risk,
      to the preterm infant.

PMID- 15495068
TI  - Disclosing to parents newborn carrier status identified by routine blood spot
      screening.
AB  - BACKGROUND: Newborn blood spot screening programmes are designed to detect
      serious conditions affecting individuals, where early treatment can improve
      health. It is suggested that screening can improve the experience of diagnosis
      for parents. For example, without newborn screening, when a child with cystic
      fibrosis becomes symptomatic a period of uncertainty can arise prior to
      diagnosis. These potential advantages of screening need to be weighed against
      potential disadvantages of screening at individual and population levels. Some
      newborn screening programmes inadvertently identify newborn infants who, although
      not affected by the condition, carry a gene for it and can pass on that gene to
      their children; these are 'genetic carriers'. Knowledge of newborn carrier status
      can lead to: testing of parents and family members, and concern about possible
      affected future siblings should both parents be identified as carriers; the
      possibility of such testing revealing the putative father is not the biological
      father; concern about the child's future reproductive choices; and unjustified
      anxiety about the health of the carrier newborn. There is an urgent need to
      develop clear guidance as to how to respond, with advances in technology fuelling
      the expansion of newborn blood spot screening and raised expectations of informed
      consent and disclosing test results. Depending on the condition for which
      screening is offered, options include: employing tests that do not identify
      carrier status, if available; identifying acceptable ways of disclosing carrier
      status; or identifying acceptable ways of not disclosing carrier status. These
      options are illustrated by screening programmes for sickle cell disorders and
      cystic fibrosis. Currently, there are no screening tests available for sickle
      cell disorders that do not identify carrier status. For cystic fibrosis, the
      policy choice is between an extended period of testing, and a screening result
      that is available sooner for most newborns, but inadvertently identifies carrier
      babies. OBJECTIVES: The aim of this review was to assess the impact of disclosing
      to parents newborn carrier status inadvertently identified by routine newborn
      blood spot screening. SEARCH STRATEGY: We searched for reports addressing
      disclosing newborn carrier status to parents following newborn screening for
      sickle cell disorders and cystic fibrosis in: commercially available electronic
      databases (October 2002), specialist registers, online journals, online abstracts
      and conference abstracts. We also scanned the reference lists of included papers.
      SELECTION CRITERIA: Studies addressing the impact of disclosing carrier status
      using a soundly controlled trial or randomised controlled trial. DATA COLLECTION
      AND ANALYSIS: Two researchers independently scanned titles and abstracts for
      relevance using the pre-specified inclusion criteria. Full reports of selected
      citations were then located and screened again for relevance by two researchers
      independently. At each stage, results were compared and discrepancies resolved by
      discussion. MAIN RESULTS: We found no controlled trials about disclosing carrier
      status. REVIEWERS' CONCLUSIONS: There is a need to develop and evaluate the
      effects of interventions to support the disclosure of carrier status to parents
      following newborn screening.

PMID- 15495069
TI  - Exercise for people with peripheral neuropathy.
AB  - BACKGROUND: Peripheral neuropathies are a wide range of diseases affecting the
      peripheral nerves. Demyelination or axonal degeneration gives rise to a variety
      of symptoms including reduced or altered sensation, pain, muscle weakness and
      fatigue. Secondary disability arises and this may result in adjustments to
      psychological and social function. Exercise therapy, with a view to developing
      strength and stamina, forms part of the treatment for people with peripheral
      neuropathy, particularly in the later stages of recovery from acute neuropathy
      and in chronic neuropathies. OBJECTIVES: The primary objective was to examine the
      effect of exercise therapy on functional ability in the treatment of people with
      peripheral neuropathy. In addition, secondary outcomes of muscle strength,
      endurance, broader measures of health and well being, as well as unfavourable
      outcomes were examined. SEARCH STRATEGY: We searched the Cochrane Neuromuscular
      Disease Group register (July 2002 and updated February 2004) and MEDLINE (from
      January 1966 to June 2004), EMBASE (from January 1980 to June 2004), CINAHL (from
      January 1982 to July 2002) and LILACS (from January 1982 to July 2002) electronic
      databases. Bibliographies of all selected randomised controlled trials were
      checked and authors contacted to identify additional published or unpublished
      data. SELECTION CRITERIA: Any randomised or quasi-randomised controlled trial
      comparing the effect of exercise therapy with no exercise therapy or drugs or an
      alternative non-drug treatment on functional ability (or disability) in people
      with peripheral neuropathy at least eight weeks after randomisation was included.
      DATA COLLECTION AND ANALYSIS: Two reviewers independently selected eligible
      studies, rated the methodological quality and extracted data. MAIN RESULTS: Only
      one trial fully met the inclusion criteria. An additional two trials assessed
      outcomes less than eight weeks after randomisation and were also included.
      Methodological quality was poor for several criteria in each study. Data used in
      the three studies could not be pooled due to heterogeneity of diagnostic groups
      and outcome measures. The results of the included trials failed to show any
      effect of strengthening and endurance exercise programmes on functional ability
      in people with peripheral neuropathy. However, there is some evidence that
      strengthening exercise programmes were moderately effective in increasing the
      strength of tested muscles. REVIEWERS' CONCLUSIONS: There is inadequate evidence
      to evaluate the effect of exercise on functional ability in people with
      peripheral neuropathy. The results suggest that progressive resisted exercise may
      improve muscle strength in affected muscles.

PMID- 15495070
TI  - Surgical treatment options for carpal tunnel syndrome.
AB  - BACKGROUND: Carpal tunnel syndrome is a common disorder, for which several
      surgical treatment options are available. OBJECTIVES: To compare the efficacy of
      the various surgical techniques in relieving symptoms and promoting return to
      work and/or activities of daily living and to compare the occurrence of side
      effects and complications, in patients suffering from carpal tunnel syndrome.
      SEARCH STRATEGY: We updated the searches in 2003. We conducted computer-aided
      searches of the trials register of the Cochrane Neuromuscular Disease Group
      (searched in July 2003), the Cochrane Central Register of Controlled Trials (The
      Cochrane Library, Issue 2, 2003), MEDLINE (January 1966 to August 2003), EMBASE
      (January 1980 to August 2003) and tracked references in bibliographies. SELECTION
      CRITERIA: Randomised controlled trials comparing various surgical techniques for
      the treatment of carpal tunnel syndrome. DATA COLLECTION AND ANALYSIS: Two
      reviewers performed study selection, assessment of methodological quality and
      data abstraction independently of each other. MAIN RESULTS: Twenty-three studies
      were included in the review. The methodological quality of the trials was fair to
      good. However, the application of allocation concealment was mentioned explicitly
      in only one trial. Many studies failed to present the results in sufficient
      detail to enable statistical pooling. Pooling was also impeded by the vast
      variety of outcome measures that were applied in the various studies. None of the
      existing alternatives to standard open carpal tunnel release seem to offer better
      relief from symptoms in the short- or long-term. There was conflicting evidence
      about whether endoscopic carpal tunnel release resulted in earlier return to work
      and/or activities of daily living than open carpal tunnel release. REVIEWERS'
      CONCLUSIONS: There is no strong evidence supporting the need for replacement of
      standard open carpal tunnel release by existing alternative surgical procedures
      for the treatment of carpal tunnel syndrome.

PMID- 15495071
TI  - Prophylactic versus selective antibiotics for term newborn infants of mothers
      with risk factors for neonatal infection.
AB  - BACKGROUND: Early onset bacterial infection is an important cause of morbidity
      and mortality in newborn infants. Various factors that increase the risk of
      neonatal infection have been identified. It is unclear whether asymptomatic
      newborn infants born to mothers with one or more of these risk factors should
      receive antibiotics prophylactically rather than selectively if only clinical or
      microbiological evidence of sepsis emerges. OBJECTIVES: To assess the effect of
      prophylactic versus selective antibiotic treatment for asymptomatic term neonates
      born to mothers with risk factors for neonatal infection. SEARCH STRATEGY: We
      used the standard methods of the Cochrane Neonatal Review Group. We searched
      MEDLINE (1966 - May 2004), EMBASE (1980 - May 2004), LILACS (1982 - 2003), SciELO
      (1997 - 2003), the Cochrane Central Register of Controlled Trials (CENTRAL, The
      Cochrane Library, Issue 2, 2004), and Centers for Disease Control and Prevention
      protocols and guidelines on the subject. SELECTION CRITERIA: Randomized
      controlled trials, or trials using quasi-random methods of allocation, comparing
      the use of prophylactic versus selective antibiotics in asymptomatic neonates
      born to mothers with one or more risk factors for infection. 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 three reviewers and synthesis of data using relative risk and risk
      difference. The pre-specified primary outcomes were neonatal mortality, systemic
      neonatal infection, and need for admission to a neonatal intensive care unit.
      MAIN RESULTS: We identified two small trials undertaken in the 1970s. Both trials
      had methodological weaknesses. There was no evidence of an effect on any of the
      primary outcomes, but because the trials were underpowered, clinically important
      effect sizes may have been missed. REVIEWERS' CONCLUSIONS: There are insufficient
      data from randomized controlled trials to guide clinical practice. A large
      randomized controlled trial is needed in asymptomatic term infants born to
      mothers with risk factors for infection in their babies, which compares the
      effect of prophylactic versus selective antibiotics on morbidity, mortality and
      costs.

PMID- 15495072
TI  - Continuous ambulatory peritoneal dialysis (CAPD) versus hospital or home
      haemodialysis for end-stage renal disease in adults.
AB  - BACKGROUND: Renal replacement therapy (RRT) with dialysis and transplantation is
      the only means of sustaining life for patients with end-stage renal disease
      (ESRD). Although transplantation is the treatment of choice, the number of donor
      kidneys are limited and transplants may fail. Hence many patients require long
      term or even life-long dialysis. Continuous ambulatory peritoneal dialysis (CAPD)
      is an alternative to hospital or home haemodialysis for patients with ESRD.
      OBJECTIVES: To assess the benefits and harms of CAPD versus hospital or home
      haemodialysis for adults with ESRD. SEARCH STRATEGY: We searched the Cochrane
      Central Register of Controlled Trials (CENTRAL in The Cochrane Library), the
      Cochrane Renal Group's specialised register, MEDLINE (1966 - May 2002), EMBASE
      (1980 - May 2002), BIOSIS, CINAHL, SIGLE and NRR without language restriction.
      Reference lists of retrieved articles and conference proceedings were searched
      and known investigators and biomedical companies were contacted. Date of most
      recent search January 2004. SELECTION CRITERIA: Randomised controlled trials
      (RCTs) or quasi-RCTs comparing CAPD to hospital or home haemodialysis for adults
      with ESRD were to be included. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently assess the methodological quality of studies. Data was abstracted
      from included studies onto a standard form by one reviewer and checked by
      another. Statistical analyses were performed using the random effects model and
      the results expressed as relative risk (RR) for dichotomous outcomes and weighted
      mean difference (WMD) for continuous outcomes with 95% confidence intervals (CI).
      MAIN RESULTS: One trial, reported in abstract form only, was located in the most
      recent search. There was no statistical difference in death or quality adjusted
      life years score at 2 years between peritoneal dialysis or haemodialysis
      patients. REVIEWERS' CONCLUSIONS: There is Insufficient data to allow conclusions
      to be drawn about the relative effectiveness of CAPD compared with hospital or
      home haemodialysis for adults with ESRD. Efforts should be made to start and
      complete adequately powered RCTs, which compare the different dialysis
      modalities.

PMID- 15495073
TI  - Rehabilitation after surgery for flexor tendon injuries in the hand.
AB  - BACKGROUND: Postoperative rehabilitation of the flexor tendons in the hand
      consists of a short period of immobilisation while pain and swelling diminish,
      followed by progressive mobilisation to maximize the range of motion of the
      affected fingers. By altering the time of immobilisation and the manner of
      subsequent mobilisation different rehabilitation regimes are created. OBJECTIVES:
      To determine, with evidence from randomised controlled trials, the optimal
      rehabilitation strategy after surgery for flexor tendon injuries in the hand.
      SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group
      specialised register (November 2002), the Cochrane Central Register of Controlled
      Trials (The Cochrane Library, issue 4, 2002), MEDLINE (1966 to November 2002),
      EMBASE (1988 to November 2002), CINAHL (1982 to October 2002), CURRENT CONTENTS
      (1993 to October 2002), PEDro - The Physiotherapy Evidence Database
      (http://ptwww.cchs.usyd.edu.au/pedro/ accessed 30/10/2002) and reference lists of
      articles. SELECTION CRITERIA: All randomised and quasi-randomised controlled
      trials of interventions for rehabilitation after surgery of flexor tendon
      injuries in the hand after surgery. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently assessed trial quality, using a 10 item scale, and extracted data
      where possible. Additional information was sought from trialists when required.
      Due to the lack of extractable data and the variety of interventions used,
      pooling was not attempted. Where possible relative risks and 95 per cent
      confidence intervals were calculated for dichotomous outcomes, and mean
      differences and 95 per cent confidence intervals calculated for continuous
      outcomes. MAIN RESULTS: Six trials, including three reported only in abstracts,
      with a total of 464 participants were included. Data were not pooled. One trial
      compared continuous passive motion (CPM) with controlled intermittent passive
      motion (CIPM) and found a significant difference in mean active motion favouring
      CPM (WMD 19.00 degrees, 95% CI 15.11 to 22.89). One trial compared a shortened
      passive flexion/active extension programme with a normal passive flexion/active
      extension mobilisation programme, and reported (without data) a significant
      reduction in absence from work of 2.1 weeks in favour of the shortened programme.
      Other trials compared active flexion with rubber band traction, early controlled
      active mobilisation with early controlled passive mobilisation and dynamic
      splintage versus static splintage. No trials found significant differences in
      overall functioning or complication rate. REVIEWERS' CONCLUSIONS: Controlled
      mobilisation regimens are widely employed in rehabilitation after flexor tendon
      repair in the hand. This review found insufficient evidence from randomised
      controlled trials to define the best mobilisation strategy.

PMID- 15495074
TI  - Oral versus intravenous antibiotic treatment for febrile neutropenia in cancer
      patients.
AB  - BACKGROUND: Fever occurring in a neutropenic patient remains a common life
      threatening complication of cancer chemotherapy. The common practice is to admit
      the patient to hospital and treat empirically with intravenous broad-spectrum
      antibiotics. Oral therapy could be an alternative approach for selected patients.
      OBJECTIVES: To compare the efficacy of oral antibiotics versus intravenous (IV)
      antibiotic therapy in febrile neutropenic cancer patients. SEARCH STRATEGY: We
      searched the Cochrane Cancer Network Register of trials (November 2002), the
      Cochrane Library (issue 2, 2002), MEDLINE (1966 to 2002), EMBASE (January 1980 to
      2002) and LILACS (1982 to 2002). We searched several databases for ongoing
      trials. We checked the conference proceedings of the Interscience Conference of
      Antimicrobial Agents and Chemotherapy (ICAAC) 1995 to 2002 and all references of
      included studies and major reviews were scanned. SELECTION CRITERIA: Randomised
      controlled trials comparing oral antibiotic/s to intravenous antibiotic/s for the
      treatment of neutropenic cancer patients with fever. The comparison between the
      two could be started initially (initial oral), or following an initial course of
      intravenous antibiotic treatment (sequential). DATA COLLECTION AND ANALYSIS: Two
      reviewers independently assessed trial eligibility, methodological quality and
      extracted data. Data concerning mortality, treatment failures and adverse events
      were extracted from included studies assuming an "intention-to-treat" basis for
      the outcome measures whenever possible. Relative risks (RR) with 95% confidence
      intervals (CI) for dichotomous data were estimated. MAIN RESULTS: Fifteen trials
      (median mortality 0, range 0 to 8.8%) were included in the analyses. The
      mortality rate was similar comparing oral to intravenous antibiotic treatment (RR
      0.91, 95% CI 0.51 to 1.62, 7 trials, 1223 patients). Treatment failure rates were
      also similar (RR 0.94, 95% CI 0.84 to 1.05, all trials). No significant
      heterogeneity was shown for all comparisons but adverse events. This effect was
      stable in a wide range of patients. Quinolones alone or combined with another
      antibiotics were used with comparable results. Adverse reactions, mostly
      gastrointestinal were more common with oral antibiotics. REVIEWERS' CONCLUSIONS:
      Based on the present data, oral treatment is an acceptable alternative to
      intravenous antibiotic treatment in febrile neutropenic cancer patients
      (excluding patients with acute leukaemia) who are haemodynamically stable,
      without organ failure, not having pneumonia, infection of a central line or a
      severe soft-tissue infection. The wide confidence interval for mortality allows
      the present use of oral treatment in groups of patients with an expected low risk
      for mortality, and further research should be aimed at clarifying the definition
      of low risk patients.

PMID- 15495075
TI  - Radiotherapy for neovascular age-related macular degeneration.
AB  - BACKGROUND: Radiotherapy has been proposed as a treatment to prevent new vessel
      growth in people with neovascular age-related macular degeneration (AMD).
      OBJECTIVES: The aim of this review was to examine the effects of radiotherapy on
      neovascular AMD. 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 2, 2004, MEDLINE (1966 to May
      2004), EMBASE (1980 to June 2004) and LILACS (Latin American and Caribbean Health
      Sciences Literature Database) (May 2004). We also wrote to investigators of
      trials included in the review to ask if they were aware of any other studies.
      SELECTION CRITERIA: We included all randomised controlled trials in which
      radiotherapy was compared to another treatment, sham treatment, low dosage
      irradiation or no treatment in people with subfoveal choroidal neovascularisation
      secondary to AMD. DATA COLLECTION AND ANALYSIS: Two reviewers independently
      extracted the data. Relative risks were combined using a random effects model.
      The percentage of the variability in effect estimates that was due to
      heterogeneity, rather than sampling error, was estimated using I2. MAIN RESULTS:
      Eleven trials randomising a total of 1078 people were included in this review.
      All trials used a similar method of delivering the radiotherapy treatment
      (external beam). Dosage ranged from 7.5 to 24 Gy. Most trials found effects (not
      always significant) that favoured treatment. However, there was considerable
      inconsistency in the results between trials (I2 > 50%). As only 11 trials were
      included in the review and only some of these trials provided data for each
      outcome our ability to determine the causes of the heterogeneity between trials
      was limited. Subgroup analyses did not reveal any statistically significant
      interactions although with small numbers of trials in each subgroup (range two to
      four) this was not surprising. There was some indication that trials with no sham
      irradiation reported a greater effect of treatment as did trials with a greater
      percentage of participants with classic choroidal neovascularisation. REVIEWERS'
      CONCLUSIONS: This review currently does not provide evidence that external beam
      radiotherapy is an effective treatment for neovascular AMD. If further trials are
      to be considered to evaluate radiotherapy in AMD then adequate masking of the
      control group must be considered. Given the recent evidence that most lesions are
      amenable to treatment with photodynamic therapy if identified at a small lesion
      size, trials evaluating radiotherapy against photodynamic therapy are warranted.

PMID- 15495076
TI  - Surgical management of pelvic organ prolapse in women.
AB  - BACKGROUND: Pelvic organ prolapse may occur in up to 50% of parous women. A
      variety of urinary, bowel and sexual symptoms may be associated with prolapse.
      OBJECTIVES: To determine the effects of surgery in the management of pelvic organ
      prolapse. SEARCH STRATEGY: We searched the Cochrane Incontinence Group trials
      register (8 June 2004) and reference lists of relevant articles. We also
      contacted researchers in the field. SELECTION CRITERIA: Randomised or quasi
      randomised controlled trials that included surgical operations for pelvic organ
      prolapse. DATA COLLECTION AND ANALYSIS: Trials were assessed and data extracted
      independently by at least two reviewers. Four investigators were contacted for
      additional information with two responding. MAIN RESULTS: Fourteen randomised
      controlled trials were identified evaluating 1004 women. Abdominal sacral
      colpopexy was better than vaginal sacrospinous colpopexy in terms of a lower rate
      of recurrent vault prolapse (RR 0.23, 95% CI 0.07 to 0.77) and less dyspareunia
      (RR 0.39, 95% CI 0.18 to 0.86), but the trend towards a lower re-operation rate
      for prolapse following abdominal sacrocolpopexy was not statistically significant
      (RR 0.46, 95% CI 0.19 to 1.11). However, the vaginal sacrospinous colpopexy was
      quicker and cheaper to perform and women had an earlier return to activities of
      daily living. The data were to evaluate other clinical outcomes and adverse
      events. For the anterior vaginal wall prolapse, standard anterior repair was
      associated with more recurrent cystoceles than when supplemented by Vicryl mesh
      overlay (RR 1.39, 95% CI 1.02 to 1.90) but data on morbidity and other clinical
      outcomes were too few for reliable comparisons. For posterior vaginal wall
      prolapse, the vaginal approach was associated with a lower rate of recurrent
      rectocele and/or enterocele than the transanal approach (RR 0.24, 95% CI 0.09 to
      0.64), although there was a higher blood loss and postoperative narcotic use.
      However, data on the effect of surgery on bowel symptoms and the use of
      polyglactin mesh overlay on the risk of recurrent rectocele were insufficient for
      meta-analysis.Meta-analysis on the impact of pelvic organ prolapse surgery on
      continence issues was limited and inconclusive, although about 10% of women
      developed new symptoms after surgery. However, more women with occult stress
      urinary incontinence developed postoperative stress urinary incontinence after
      endopelvic fascia plication alone than after endopelvic fascia plication and
      tension-free vaginal tape (RR 5.5, 95% CI 1.36 to 22.32). REVIEWERS' CONCLUSIONS:
      Abdominal sacrocolpopexy is associated with a lower rate of recurrent vault
      prolapse and dyspareunia than the vaginal sacrospinous colpopexy. These benefits
      must be balanced against a longer operating time, longer time to return to
      activities of daily living and increased cost of the abdominal approach. The use
      of a polyglactin mesh overlay at the time of anterior vaginal wall repair may
      reduce the risk of recurrent cystocele. Posterior vaginal wall repair may be
      better than transanal repair in the management of rectoceles in terms of
      recurrence of prolapse. Adequately powered randomised controlled clinical trials
      are urgently needed.

PMID- 15495077
TI  - Vaginal chlorhexidine during labour for preventing maternal and neonatal
      infections (excluding Group B Streptococcal and HIV).
AB  - BACKGROUND: The incidence of chlorioamnionitis occurs in between 8 to 12 women
      for every 1000 live births and 96% of the cases of chlorioamnionitis are due to
      ascending infection. Following spontaneous vaginal delivery, 1% to 4% of women
      develop postpartum endometritis. The incidence of neonatal sepsis is 0.5% to 1%
      of all infants born. Maternal vaginal bacteria are the main agents for these
      infections. It is reasonable to speculate that prevention of maternal and
      neonatal infections might be possible by washing the vagina and cervix with an
      antibacterial agent for all women during labour. Chlorhexidine belongs to the
      class of compounds known as the bis-biguanides. Chlorhexidine has antibacterial
      action against a wide range of aerobic and anaerobic bacteria, including those
      implicated in peripartal infections. OBJECTIVES: To evaluate the effectiveness
      and side-effects of chlorhexidine vaginal douching during labour in reducing
      maternal and neonatal infections (excluding Group B Streptococcal and HIV).
      SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials
      register (July 2003), the Cochrane Central Register of Controlled Trials (The
      Cochrane Library, Issue 4, 2002), MEDLINE (from 1966 to 2002), EMBASE (from 1980
      to 2002), CINAHL (from 1982 to 2002) and LILACS (from 1982 to 2002). SELECTION
      CRITERIA: Randomized or quasi-randomized trials comparing chlorhexidine vaginal
      douching during labour with placebo or other vaginal disinfectant to prevent
      (reduce) maternal and neonatal infections (excluding Group B Streptococcal and
      HIV). DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial
      eligibility and quality, extracted and entered the data into the RevMan software
      and interpreted the data. A third reviewer analysed and interpreted the data. The
      fourth reviewer also interpreted the data. MAIN RESULTS: Three studies (3012
      participants) were included. There was no evidence of an effect of vaginal
      chlorhexidine during labour in preventing maternal and neonatal infections.
      Although the data suggest a trend in reducing postpartum endometritis, the
      difference was not statistically significant (relative risk 0.83; 95% confidence
      interval 0.61 to 1.13). REVIEWERS' CONCLUSIONS: There is no evidence to support
      the use of vaginal chlorhexidine during labour in preventing maternal and
      neonatal infections. There is a need for a well-designed randomized controlled
      trial using appropriate concentration and volume of vaginal chlorhexidine
      irrigation solution and with adequate sample size.

PMID- 15495078
TI  - Fetal pulse oximetry for fetal assessment in labour.
AB  - BACKGROUND: Fetal pulse oximetry (FPO) may contribute to the evaluation of fetal
      well-being during labour. OBJECTIVES: To compare the effectiveness and safety of
      FPO with conventional surveillance techniques, using the results of randomised
      controlled trials. SEARCH STRATEGY: We searched the Cochrane Pregnancy and
      Childbirth Group trials register (31 July 2004) and conducted a systematic
      literature search of MEDLINE (1994 to July 2004), EMBASE (1994 to July 2004) and
      Current Contents (1994 to July 2004). SELECTION CRITERIA: All published and
      unpublished randomised controlled trials (RCTs) that compared maternal and
      fetal/neonatal/infant outcomes when FPO was used in labour, with or without
      concurrent use of conventional fetal surveillance, compared with using
      cardiotocography (CTG) alone. DATA COLLECTION AND ANALYSIS: Two independent
      reviewers performed data extraction. Analyses were performed on an intention-to
      treat basis. We sought additional information from the investigators of the one
      reported trial. MAIN RESULTS: One published RCT (comparing FPO and CTG with CTG
      alone) was included; and two ongoing RCTs were identified. The single included
      RCT reported on 1010 cases. Unpublished pilot data were available for some
      outcomes to give a total of 1190 cases. There was no difference in the overall
      caesarean section rate between the two groups (relative risk (RR) 1.12, 95%
      confidence interval (CI) 0.91 to 1.37). There were less caesarean sections for
      nonreassuring fetal status in the FPO plus CTG group compared with the CTG only
      group (RR 0.45, 95% CI 0.28 to 0.72). The only reported neonatal seizure occurred
      in the CTG only group (RR 0.29 95% CI 0.01 to 7.08). Use of FPO with CTG
      decreased operative delivery (caesarean section, forceps, vacuum) for
      nonreassuring fetal status (RR 0.71, 95% CI 0.55 to 0.93) compared with CTG
      alone. No differences were seen for overall operative deliveries, endometritis,
      intrapartum or postpartum haemorrhage, uterine rupture, low Apgar scores,
      umbilical arterial pH or base excess, admission to the neonatal intensive care
      unit or fetal/neonatal death. REVIEWERS' CONCLUSIONS: The one published RCT
      reported that FPO decreased the caesarean section rate and operative delivery
      rates for nonreassuring fetal status, without adversely affecting maternal or
      fetal/neonatal outcomes. However, no difference was seen in the overall caesarean
      section (CS) or operative delivery rates because more CS were performed for
      dystocia in the FPO group. Further RCTs may address dystocia in labours monitored
      with FPO, maternal satisfaction with fetal monitoring and labour, long-term
      neurodevelopmental outcome of infants who exhibited nonreassuring fetal status in
      labour and costs of FPO.

PMID- 15495079
TI  - Force platform feedback for standing balance training after stroke.
AB  - BACKGROUND: Standing balance deficits are common in individuals after stroke. One
      way to address these deficits is to provide the individual with feedback from a
      force platform while balance activities are performed. The feedback can take
      visual and/or auditory form. OBJECTIVES: To determine if visual or auditory force
      platform feedback improves the clinical and force platform standing balance
      outcomes in clients with stroke. SEARCH STRATEGY: We searched the Cochrane Stroke
      Group trials register (last searched December 2003), and the following electronic
      bibliographic databases: the Cochrane Central Register of Controlled Trials (The
      Cochrane Library Issue 3, 2003), MEDLINE (1966 to May 2003), EMBASE (1974 to May
      2003), CINAHL (1982 to May 2003), PEDro (May 2003), CIRRIE (May 2003) and
      REHABDATA (May 2003). Reference lists of articles were reviewed and manufacturers
      of equipment were contacted. SELECTION CRITERIA: Randomized controlled trials
      comparing force platform with visual feedback and/or auditory feedback to other
      balance treatments. DATA COLLECTION AND ANALYSIS: Two reviewers independently
      assessed trials for inclusion, methodological quality, and data extraction.
      Trials were combined for meta-analysis according to outcome and type of feedback.
      MAIN RESULTS: We included seven trials (246 participants). Force platform
      feedback did not improve clinical measures of balance when moving or walking
      (Berg Balance Scale and Timed Up and Go). Significant improvements in laboratory
      force platform indicators of stance symmetry were found for regimens using visual
      feedback (standardised mean difference (SMD) -0.68, 95% confidence interval (CI) 
      1.31 to -0.04, p = 0.04) and the concurrent visual and auditory feedback
      (weighted mean difference (WMD) -4.02, 95% CI -5.99 to -2.04, p = 0.00007). There
      were no significant effects on laboratory postural sway indicators, clinical
      outcomes or measures of function at follow-up assessment. REVIEWERS' CONCLUSIONS:
      Force platform feedback (visual or auditory) improved stance symmetry but not
      sway in standing, clinical balance outcomes or measures of independence.

PMID- 15495080
TI  - Substitution treatment of injecting opioid users for prevention of HIV infection.
AB  - BACKGROUND: Injecting drug users are vulnerable to infection with HIV and other
      blood borne viruses as a result of collective use of injecting equipment as well
      as sexual behaviour. OBJECTIVES: To assess the effect of oral substitution
      treatment for opioid dependent injecting drug users on rates of HIV infections,
      and high risk behaviours. SEARCH STRATEGY: Multiple electronic databases were
      searched. Reference lists of retrieved studies, reviews and conference abstracts
      were handsearched. SELECTION CRITERIA: Studies were required to consider the
      incidence of risk behaviours, or the incidence of HIV infection related to
      substitution treatment of opioid dependence. All types of original studies were
      considered. DATA COLLECTION AND ANALYSIS: Each potentially relevant study was
      independently assessed by two reviewers. For studies that met the inclusion
      criteria, key information was extracted by one reviewer and confirmed by
      consultation between all four reviewers. MAIN RESULTS: Twenty-eight studies,
      involving 7900 participants, were included. The majority were not randomised
      controlled studies. Issues of confounding and bias are discussed. The studies
      varied in several aspects limiting the extent of quantitative analysis.
      REVIEWERS' CONCLUSIONS: Oral substitution treatment for opioid-dependent
      injecting drug users is associated with statistically significant reductions in
      illicit opioid use, injecting use and sharing of injecting equipment. It is also
      associated with reductions in the proportion of injecting drug users reporting
      multiple sex partners or exchanges of sex for drugs or money, but has little
      effect on condom use. It appears that the reductions in risk behaviours related
      to drug use do translate into reductions in cases of HIV infection. The lack of
      data from randomised controlled studies limits the strength of the evidence
      presented in this review. However, these findings add to the stronger evidence of
      effectiveness of substitution treatment on drug use, and treatment retention
      outcomes shown by other systematic reviews. On this basis, the provision of
      substitution treatment for opioid dependence in countries with emerging HIV and
      injecting drug use problems as well as in countries with established populations
      of injecting drug users should be supported.

PMID- 15495081
TI  - Psychosocial combined with agonist maintenance treatments versus agonist
      maintenance treatments alone for treatment of opioid dependence.
AB  - BACKGROUND: Methadone maintenance at proper doses is effective in retaining
      patients in treatment and suppressing heroin use. Questions remain regarding the
      efficacy of the psychosocial services that are offered by most maintenance
      programs. OBJECTIVES: To evaluate the effectiveness of any psychosocial plus any
      agonist maintenance treatment versus any agonist treatment alone in retaining
      patients in treatment, reducing the use of substances and improving health and
      social status. SEARCH STRATEGY: We searched the Cochrane Central Register of
      Trials (CENTRAL) issue 3, 2003; MEDLINE 1966-2003; EMBASE 1980-2003; PsycINFO
      1985-2003; relevant web sites; scan of reference list of relevant articles. There
      were no language or publication restrictions. SELECTION CRITERIA: RCTs which
      focus on any psychosocial plus any agonist compared to any agonist maintenance
      intervention for opiate dependence. People aged less than 18 and pregnant women
      were excluded. Psychosocial in combination with antagonist maintenance treatment
      are excluded too. DATA COLLECTION AND ANALYSIS: The trials were independently
      assessed for inclusion and methodological quality by the reviewers. Data were
      extracted independently and double checked. MAIN RESULTS: The searching process
      resulted in the identification of 77 different studies: 12 studies met the
      inclusion criteria. These studies considered 8 different psychosocial
      interventions and 1 pharmacological treatment: Methadone Maintenance (MMT). The
      results show additional benefit in adding any psychosocial treatment to standard
      methadone maintenance treatment in relation to the use of heroin during the
      treatment RR 0.69 (95% CI 0.53-0.91); no statistically significant additional
      benefit was shown in terms of retention in treatment RR 0.94 (95% CI 0.85-1.02);
      and results at follow-up RR 0.90 (95% CI 0.76-1.07). REVIEWERS' CONCLUSIONS: The
      present evidence suggests that adding any psychosocial support to Standard MMT
      significantly improves the non-use of heroin during treatment. Retention in
      treatment and results at follow-up are also improved, although this findings did
      not achieve statistical significance. Insufficient evidence is available on other
      possible relevant outcomes such as Psychiatric symptoms/psychological distress,
      Quality of life. Limitations to this review are imposed by the heterogeneity of
      the trials both in the interventions and the assessment of outcomes. Results of
      studies were sometimes in disagreement and because of lack of detailed
      information no meta analysis could be performed to analyse the results related to
      the outcomes more often reported as positive results in the single studies.
      Duration of the studies was also too short to analyse other relevant outcomes
      such as mortality. In order to study the possible added value of any psychosocial
      treatment over an already effective treatment such as standard MMT, only big
      multi-site studies could be considered which define experimental interventions
      and outcomes in the most standardized way as possible.

PMID- 15495082
TI  - Alcohol ignition interlock programmes for reducing drink driving recidivism.
AB  - BACKGROUND: An ignition interlock device is part of a multi-dimensional programme
      aimed at reducing recidivism in convicted drink drivers. To operate a vehicle
      equipped with an ignition interlock device, the driver must first provide a
      breath specimen. If the breath alcohol concentration of the specimen exceeds the
      predetermined level, the vehicle will not start. As a measure to reduce
      circumvention of the device (i.e. someone else blows into the mouthpiece), random
      retests are required while the vehicle is running. Other components of the drink
      driving programme include information seminars for the driver and downloading
      data from the device's data logger, which logs all test attempts and records all
      passes, warnings and failures. OBJECTIVES: To systematically assess the
      effectiveness of ignition interlock programmes on recidivism rates of drink
      drivers, by examining rates of recidivism while the ignition interlock device was
      installed in the vehicle and after removal of the device. SEARCH STRATEGY: The
      Cochrane Controlled Trials Register was searched, in addition to relevant
      electronic databases and the Internet. SELECTION CRITERIA: Controlled trials in
      which offenders have been charged with drink driving and have either been
      sentenced to participate in an ignition interlock programme or the usual
      punishment (either licence suspension or some form of treatment programme). This
      study was not restricted by language or status of publication. DATA COLLECTION
      AND ANALYSIS: One randomised controlled trial (RCT) and ten controlled trials
      were identified, and also three ongoing trials. Data regarding recidivism while
      the interlock is installed in the vehicle; after the interlock has been removed
      from the vehicle and total recidivism during the study were extracted and entered
      into analyses using RevMan. MAIN RESULTS: The RCT showed that the interlock
      programme was effective while the device was installed in the vehicle; relative
      risk 0.36 (95% confidence interval 0.21 to 0.63). Controlled trials support this
      conclusion, with a general trend - in both first-time and repeat offenders -
      towards lower recidivism rates when the interlock device is installed. Neither
      the RCT nor the controlled trials provide evidence for any effectiveness of the
      programmes continuing once the device has been removed. REVIEWERS' CONCLUSIONS:
      In order to eliminate potential selection bias, more RCTs need to be conducted in
      this area so that effectiveness, as well as efficacy, can be ascertained. The
      interlock programme appears to be effective while the device is installed in the
      vehicle of the offender. Studies need to address ways of improving recidivism
      rates in the long term, as the major challenges are participation rates,
      compliance and durability.

PMID- 15495083
TI  - Telephone consultation and triage: effects on health care use and patient
      satisfaction.
AB  - BACKGROUND: Telephone consultation is the process where calls are received,
      assessed and managed by giving advice or by referral to a more appropriate
      service. In recent years there has been a growth in telephone consultation
      developed, in part, as a response to increased demand for General Practitioner
      (GP) and Accident and Emergency (A&E) department care. OBJECTIVES: To assess the
      effects of telephone consultation on safety, service usage and patient
      satisfaction and to compare telephone consultation by different health care
      professionals. SEARCH STRATEGY: We searched the Cochrane Central Register of
      Controlled Trials, the specialised register of the Cochrane Effective Practice
      and Organisation of Care (EPOC) group, Pubmed, EMBASE, CINAHL, SIGLE, and the
      National Research Register. We checked reference lists of identified studies and
      review articles and contacted experts in the field. The search was not restricted
      by language or publication status. SELECTION CRITERIA: Randomised controlled
      trials (RCTs), controlled studies, controlled before/after studies (CBAs) and
      interrupted time series (ITSs) of telephone consultation or triage in a general
      health care setting. Disease specific phone lines were excluded. DATA COLLECTION
      AND ANALYSIS: Two reviewers independently screened studies for inclusion in the
      review, extracted data and assessed study quality. Data were collected on adverse
      events, service usage, cost and patient satisfaction. Due to heterogeneity we did
      not pool studies in a meta-analysis and instead present a narrative summary of
      the findings. MAIN RESULTS: Nine studies met our inclusion criteria, five RCTs,
      one CCT and three ITSs. Six studies compared telephone consultation versus normal
      care; four by a doctor, one by a nurse and one by a clinic clerk. Three studies
      compared telephone consultation by different types of health care workers; two
      compared nurses with doctors and one compared health assistants with doctors or
      nurses. Three of five studies found a decrease in visits to GP's but two found a
      significant increase in return consultations. In general at least 50% of calls
      were handled by telephone advice alone. Seven studies looked at accident and
      emergency department visits, six showed no difference between the groups and one,
      of nurse telephone consultation, found an increase in visits. Two studies
      reported deaths and found no difference between nurse telephone triage and normal
      care. REVIEWERS' CONCLUSIONS: Telephone consultation appears to reduce the number
      of surgery contacts and out-of-hours visits by general practitioners. However,
      questions remain about its affect on service use and further rigorous evaluation
      is needed with emphasis on service use, safety, cost and patient satisfaction.

PMID- 15495084
TI  - Antioxidant supplements for preventing gastrointestinal cancers.
AB  - BACKGROUND: Oxidative stress may cause gastrointestinal cancers. The evidence on
      whether antioxidant supplements are effective in preventing gastrointestinal
      cancers is contradictory. OBJECTIVES: To assess the beneficial and harmful
      effects of antioxidant supplements in preventing gastrointestinal cancers. SEARCH
      STRATEGY: We identified trials through the trials registers of the four Cochrane
      Review Groups on gastrointestinal diseases, The Cochrane Central Register of
      Controlled Trials on The Cochrane Library (Issue 1, 2003), MEDLINE, EMBASE,
      LILACS, and SCI-EXPANDED from inception to February 2003, and The Chinese
      Biomedical Database (March 2003). We scanned reference lists and contacted
      pharmaceutical companies. SELECTION CRITERIA: Randomised trials comparing
      antioxidant supplements to placebo/no intervention examining the incidence of
      gastrointestinal cancers. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently selected trials for inclusion and extracted data. The outcome
      measures were incidence of gastrointestinal cancers, overall mortality, and
      adverse events. Outcomes were reported as relative risks (RR) with 95% confidence
      interval (CI) based on fixed and random effects meta-analyses. MAIN RESULTS: We
      identified 14 randomised trials (170,525 participants), assessing beta-carotene
      (9 trials), vitamin A (4 trials), vitamin C (4 trials), vitamin E (5 trials), and
      selenium (6 trials). Trial quality was generally high. Heterogeneity was low to
      moderate. Neither the fixed effect (RR 0.96, 95% CI 0.88 to 1.04) nor random
      effects meta-analyses (RR 0.90, 95% CI 0.77 to 1.05) showed significant effects
      of supplementation with antioxidants on the incidences of gastrointestinal
      cancers. Among the seven high-quality trials reporting on mortality (131,727
      participants), the fixed effect (RR 1.06, 95% CI 1.02 to 1.10) unlike the random
      effects meta-analysis (RR 1.06, 95% CI 0.98 to 1.15) showed that antioxidant
      supplements significantly increased mortality. Two low-quality trials (32,302
      participants) found no significant effect of antioxidant supplementation on
      mortality. The difference between the mortality estimates in high- and low
      quality trials was significant by test of interaction (z = 2.10, P = 0.04). Beta
      carotene and vitamin A (RR 1.29, 95% CI 1.14 to 1.45) and beta-carotene and
      vitamin E (RR 1.10, 95% CI 1.01 to 1.20) significantly increased mortality, while
      beta-carotene alone only tended to do so (RR 1.05, 95% CI 0.99 to 1.11).
      Increased yellowing of the skin and belching were non-serious adverse effects of
      beta-carotene. In four trials (three with unclear/inadequate methodology),
      selenium showed significant beneficial effect on gastrointestinal cancer
      incidences. REVIEWERS' CONCLUSIONS: We could not find evidence that antioxidant
      supplements prevent gastrointestinal cancers. On the contrary, they seem to
      increase overall mortality. The potential cancer preventive effect of selenium
      should be studied in adequately conducted randomised trials.

PMID- 15495085
TI  - Treatments for priapism in boys and men with sickle cell disease.
AB  - BACKGROUND: Sickle cell disease comprises a group of genetic haemoglobin
      disorders. The predominant symptom associated with sickle cell disease is pain
      resulting from the occlusion of small blood vessels by abnormally 'sickle-shaped'
      red blood cells. There are other complications, including chronic organ damage
      and prolonged painful erection of the penis, known as priapism. Severity of
      sickle cell disease is variable, and treatment is usually symptomatic. Priapism
      affects up to half of all men with sickle cell disease, however there is no
      consistency in treatment. We therefore need to know the best way of treating this
      complication in order to offer an effective interventional approach to all
      affected individuals. OBJECTIVES: To assess the benefits and risks of different
      treatments for stuttering (repeated short episodes) and fulminant (lasting for
      six hours or more) priapism in sickle cell disease. SEARCH STRATEGY: We searched
      the Cochrane Cystic Fibrosis and Genetic Disorders Group trials register, which
      comprises references identified from comprehensive electronic database searches
      and handsearches of relevant journals and abstract books of conference
      proceedings. We also searched the internet for further references. Date of the
      most recent search of the Group's trials register: August 2004. SELECTION
      CRITERIA: All randomised or quasi-randomised controlled trials comparing non
      surgical or surgical treatment with placebo or no treatment, or with another
      intervention for stuttering or fulminant priapism. DATA COLLECTION AND ANALYSIS:
      The reviewers independently extracted data and assessed study quality. MAIN
      RESULTS: Only one study of 11 participants was identified and met the criteria
      for inclusion in this review. This study compared stilboestrol to placebo. The
      only outcome specified in this review, which was assessed in the study, was
      reduction in frequency of stuttering priapism and there was no difference between
      the groups, relative risk 0.18 (95%CI 0.01 to 2.54). REVIEWERS' CONCLUSIONS:
      There is no evidence for the benefits or risks of the different treatments for
      both stuttering and fulminant priapism in sickle cell disease. This systematic
      review has clearly identified the need for well-designed, adequately-powered,
      multicentre randomised controlled trials assessing the effectiveness of specific
      interventions for priapism in sickle cell disease.

PMID- 15495086
TI  - Pain relief for neonatal circumcision.
AB  - BACKGROUND: Circumcision is a painful procedure that many newborn males undergo
      in the first few days after birth. Interventions are available to reduce pain at
      circumcision; however, many newborns are circumcised without pain management.
      OBJECTIVES: The objective of this review was to assess the effectiveness and
      safety of interventions for reducing pain at neonatal circumcision. SEARCH
      STRATEGY: We searched Cochrane Central Register of Controlled Trials (CENTRAL,
      The Cochrane Library, Issue 2, 2004), MEDLINE (1966 - April 2004), EMBASE (1988 -
      2004 week 19), CINAHL (1982 - May week 1 2004), Dissertation Abstracts (1986 -
      May 2004), Proceedings of the World Congress on Pain (1993 - 1999), and reference
      lists of articles. Language restrictions were not imposed. SELECTION CRITERIA:
      Randomised controlled trials comparing pain interventions with placebo or no
      treatment or comparing two active pain interventions in male term or preterm
      infants undergoing circumcision. DATA COLLECTION AND ANALYSIS: Two independent
      reviewers assessed trial quality and extracted data. Ten authors were contacted
      for additional information. Adverse effects information was obtained from the
      trial reports. For meta-analysis, data on a continuous scale were reported as
      weighted mean difference (WMD) or, when the units were not compatible, as
      standardized mean difference. MAIN RESULTS: Thirty-five trials involving 1,984
      newborns were included. Thirty-three trials enrolled healthy, full term neonates,
      and two enrolled infants born preterm. Fourteen trials involving 592 newborns
      compared dorsal penile nerve block (DPNB) with placebo or no treatment. Compared
      to placebo/no treatment, DPNB demonstrated significantly lower heart rate [WMD 
      35 bpm, 95% CI -41 to -30], decreased time crying [WMD -54 %, 95% CI -64 to -44],
      and increased oxygen saturation [WMD 3.2 %, 95% CI 2.7 to 3.7]. Six trials
      involving 190 newborns compared eutectic mixture of analgesics (EMLA) with
      placebo. EMLA demonstrated significantly lower facial action scores [WMD -46.5,
      95% CI -80.4 to -12.6], decreased time crying [WMD - 15.8 %, 95% CI -20.8 to 
      6.8] and lower heart rate [WMD -15 bpm, 95% CI -19 to -10]. DPNB, compared with
      EMLA in four trials involving 164 newborns, demonstrated significantly lower
      heart rate [WMD -17 bpm, 95% CI -23 to -11] and pain scores. When compared with
      sucrose in two trials involving 126 newborns, DPNB demonstrated less time crying
      [MD -166 s, 95% CI -211 to -121], and lower heart rate [WMD -27 bpm, 95% CI -33
      to -20]. Results obtained for trials comparing oral sucrose and oral analgesics
      to placebo, and trials of environmental modification were either inconsistent or
      were not significantly different. Adverse effects included gagging, choking, and
      emesis in placebo/untreated groups. Minor bleeding, swelling and hematoma were
      reported with DPNB. Erythema and mild skin pallor were observed with the use of
      EMLA. Methaemoglobin levels were evaluated in two trials of EMLA, and results
      were within normal limits. REVIEWERS' CONCLUSIONS: DPNB was the most frequently
      studied intervention and was the most effective for circumcision pain. Compared
      to placebo, EMLA was also effective, but was not as effective as DPNB. Both
      interventions appear to be safe for use in newborns. None of the studied
      interventions completely eliminated the pain response to circumcision.

PMID- 15495087
TI  - Anticonvulsants for neonates with seizures.
AB  - BACKGROUND: Neonatal seizures are a common problem and most neonates with
      seizures are treated with anticonvulsants. There is wide variation in clinical
      practice in both diagnosis and treatment of such seizures and this reflects the
      lack of clear evidence of the relative benefit and harm of the anticonvulsants
      used. The routine use of anticonvulsants to treat seizures in neonates needs to
      be evaluated. OBJECTIVES: To assess and compare (with respect to benefits and
      harm) different anticonvulsants administered to neonates for the treatment of
      established seizures. SEARCH STRATEGY: Relevant randomised controlled trials were
      identified using a combination of electronic database searches (MEDLINE 1966 -
      March 2004, EMBASE 1980 - March 2004), the Cochrane Central Register of
      Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2004) and hand
      searches. Identification of ongoing or unpublished trials was attempted by
      contacting prominent authors in the field and searching electronic registers of
      ongoing trials. SELECTION CRITERIA: All randomised or quasi-randomised controlled
      clinical trials with reported data comparing the following outcomes: mortality,
      neurodevelopmental disability, need for additional anticonvulsants, need for
      maintenance anticonvulsants at discharge and adverse events (hypotension
      requiring volume or inotropic support, arrhythmia, respiratory depression,
      hepatotoxicity) in neonates treated for seizures with systemic anticonvulsants
      compared to placebo, no drug or alternative anticonvulsants. DATA COLLECTION AND
      ANALYSIS: Methodological quality and validity were assessed without consideration
      of the results. The first reviewer screened the title and abstracts of studies
      identified by the above search strategy. Full text versions of studies of
      potential relevance were re-screened by both reviewers. Studies meeting the pre
      specified inclusion criteria were included. Relevant data were extracted and
      analysed separately and any disagreements were resolved by discussion. MAIN
      RESULTS: Only two randomised controlled trials published in full could be
      identified. Painter 1999 showed that both of the two most commonly used
      anticonvulsants (phenobarbital and phenytoin) were similarly effective (RR 1.03
      95% CI 0.96 to 1.62), controlling seizures in less than fifty percent of infants.
      Painter 1999 did not report mortality or neurodevelopmental outcome. Boylan 2004
      randomised infants who failed to respond to phenobarbital to receive either
      lidocaine or midazolam as second-line agents. There was a trend for lidocaine to
      be more effective in reducing seizure burden (RR 0.40 95% CI 0.14 to 1.17) but
      both groups had similarly poor long term outcomes assessed at one year.
      REVIEWERS' CONCLUSIONS: At present there is little evidence from randomised
      controlled trials to support the use of any of the anticonvulsants currently used
      in the neonatal period. In the literature, there remains a body of opinion that
      seizures should be treated because of the concern that seizures in themselves may
      be harmful, although this is only supported by relatively low grade evidence
      (Levene 2002; Massingale 1993). Development of safe and effective treatment
      strategies relies on future studies of high quality (randomised controlled trials
      with methodology that assures validity) and of sufficient size to have the power
      to detect clinically important reductions in mortality and severe
      neurodevelopmental disability in addition to any short term reduction in seizure
      burden.

PMID- 15495088
TI  - Buccal or sublingual misoprostol for cervical ripening and induction of labour.
AB  - BACKGROUND: This is one of a series of reviews of cervical ripening and labour
      induction using standardised methodology. Misoprostol administered by the oral
      and sublingual routes have the advantage of rapid onset of action, while the
      sublingual and vaginal routes have the advantage of prolonged activity and
      greatest bioavailability. OBJECTIVES: To determine the effectiveness and safety
      of misoprostol administered buccally or sublingually for third trimester cervical
      ripening and induction of labour. SEARCH STRATEGY: We searched the Cochrane
      Pregnancy and Childbirth Group trials register (8 December 2003), the Cochrane
      Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2003), and
      bibliographies of relevant papers. SELECTION CRITERIA: Randomised controlled
      trials comparing buccal or sublingual misoprostol used for third trimester
      cervical ripening or labour induction with placebo/no treatment or other methods
      listed above it on a predefined list of labour induction methods. DATA COLLECTION
      AND ANALYSIS: A generic strategy was developed to deal with the large volume and
      complexity of trial data relating to labour induction. Data were extracted onto
      standardized forms, checked for accuracy, and analysed using RevMan software.
      MAIN RESULTS: Three studies (502 participants) compared buccal/sublingual
      misoprostol respectively with a vaginal regimen (200 microg versus 50 microg) and
      with oral administration (50 versus 50 microg and 50 versus 100microg).The buccal
      route was associated with a trend to fewer caesarean sections than with the
      vaginal route (18/73 versus 28/79; relative risk (RR) 0.70; 95% confidence
      interval (CI) 0.42 to 1.15). There were no significant differences in any other
      outcomes. When the same dosage was used sublingually versus orally, the
      sublingual route was associated with less failures to achieve vaginal delivery
      within 24 hours (12/50 versus 19/50; RR 0.63, 95% CI 0.34 to 1.16), reduced
      oxytocin augmentation (17/50 versus 23/50; RR 0.74, 95% CI 0.45 to 1.21) and
      reduced caesarean section (8/50 versus 15/50; RR 0.53, 95% CI 0.25 to 1.14), but
      the differences were not statistically significant. When a smaller dose was used
      sublingually than orally, there were no differences in any of the outcomes.
      REVIEWERS' CONCLUSIONS: Based on only three small trials, sublingual misoprostol
      appears to be at least as effective as when the same dose is administered orally.
      There are inadequate data to comment on the relative complications and side
      effects. Sublingual or buccal misoprostol should not enter clinical use until its
      safety and optimal dosage have been established by larger trials.

PMID- 15495089
TI  - Treatment for women with postpartum iron deficiency anaemia.
AB  - BACKGROUND: Postpartum anaemia is associated with breathlessness, tiredness,
      palpitations and maternal infections. Blood transfusions or iron supplementation
      have been used in the treatment of iron deficiency anaemia. Recently other
      anaemia treatments, in particular erythropoietin therapy, have also been used.
      OBJECTIVES: To assess the clinical effects of treatments for postpartum anaemia,
      including oral, intravenous or subcutaneous iron/folate supplementation and
      erythropoietin administration, and blood transfusion. 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), MEDLINE (1966 to March 2003), EMBASE (1980 to March 2003),
      Current Contents and ACP Journal Club (from inception to March 2003). SELECTION
      CRITERIA: Randomised controlled trials (RCTs) comparing therapy for postpartum
      iron deficiency anaemia (oral, intravenous or subcutaneous administration of
      iron, folate, erythropoietin or blood transfusion) with placebo, another
      treatment or no treatment. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently assessed trial quality and extracted data. MAIN RESULTS: Six
      included RCTs involving 411 women described treatment with erythropoietin or iron
      as their primary interventions. No RCTs were identified that assessed treatment
      with blood transfusion. Few outcomes relating to clinical maternal and neonatal
      factors were reported: studies focused largely on surrogate outcomes such as
      haematological indices. Overall, the methodological quality of the included RCTs
      was reasonable; however, their usefulness in this review is restricted by the
      interventions and outcomes reported. When compared with iron therapy only,
      erythropoietin increased the likelihood of lactation at discharge from hospital
      (1 RCT, n = 40; relative risk (RR) 1.90, 95% confidence interval (CI) 1.21 to
      2.98). No apparent effect on need for blood transfusions was found, when
      erythropoietin plus iron was compared to treatment with iron only (2 RCTs, n =
      100; RR 0.20, 95% CI 0.01 to 3.92), although the RCTs may have been of
      insufficient size to rule out important clinical differences. Haematological
      indices (haemoglobin and haemocrit) showed some increases when erythropoietin was
      compared to iron only, iron and folate, but not when compared with placebo.
      REVIEWERS' CONCLUSIONS: There is some limited evidence of favourable outcomes for
      treatment of postpartum anaemia with erythropoietin. However, most of the
      available literature focuses on laboratory haematological indices, rather than
      clinical outcomes. Further high-quality trials assessing the treatment of
      postpartum anaemia with iron supplementation and blood transfusions are required.
      Future trials may also examine the significance of the severity of anaemia in
      relation to treatment, and an iron-rich diet as an intervention.

PMID- 15495090
TI  - Planned elective repeat caesarean section versus planned vaginal birth for women
      with a previous caesarean birth.
AB  - BACKGROUND: When a woman has had a previous caesarean birth, there are two
      options for her care in a subsequent pregnancy: planned elective repeat caesarean
      or planned vaginal birth. While there are risks and benefits for both planned
      elective repeat caesarean birth and planned vaginal birth after caesarean,
      current sources of information are limited to non-randomised cohort studies.
      Studies designed in this way have significant potential for bias and consequently
      conclusions based on these results are limited in their reliability and should be
      interpreted with caution. OBJECTIVES: To assess, using the best available
      evidence, the benefits and harms of a policy of planned elective repeat caesarean
      section with a policy of planned vaginal birth after caesarean section for women
      with a previous caesarean birth. SEARCH STRATEGY: We searched the Cochrane
      Pregnancy and Childbirth Group trials register (24 June 2004), the Cochrane
      Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2004), and
      PubMed (1966 to 24 June 2004). SELECTION CRITERIA: Randomised controlled trials
      with reported data that compared outcomes in mothers and babies who planned a
      repeat elective caesarean section with outcomes in women who planned a vaginal
      birth, where a previous birth had been by caesarean. DATA COLLECTION AND
      ANALYSIS: Two reviewers independently assessed trial quality and extracted data.
      MAIN RESULTS: There were no randomised controlled trials identified. REVIEWERS'
      CONCLUSIONS: Planned elective repeat caesarean section and planned vaginal birth
      after caesarean section for women with a prior caesarean birth are both
      associated with benefits and harms. Evidence for these care practices is drawn
      from non-randomised studies, associated with potential bias. Any results and
      conclusions must therefore be interpreted with caution. Randomised controlled
      trials are required to provide the most reliable evidence regarding the benefits
      and harms of both planned elective repeat caesarean section and planned vaginal
      birth for women with a previous caesarean birth.

PMID- 15495092
TI  - Progressive resistive exercise interventions for adults living with HIV/AIDS.
AB  - BACKGROUND: Due to medical advancements, many people living with HIV infection in
      developed countries are living longer (Palella 1998). HIV infection can now
      present as a chronic illness with an uncertain natural disease history. The
      changing course of HIV infection has lead to a potential increase in the
      prevalence and impact of disability in people living with HIV infection. Exercise
      is one key management strategy used by health care professionals to address
      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 experience in life
      situations such as inability to work) in this population (World Health
      Organization 2001). Exercise may also be used to address unwanted changes in
      weight and body composition in people living with HIV infection. Aerobic exercise
      has been associated with improvements in strength, cardiovascular function, and
      psychological status in general populations (Bouchard 1993). Results of a
      systematic review suggested that aerobic exercise interventions appeared to be
      safe and may lead to improvements in cardiopulmonary fitness for adults living
      with HIV/AIDS (Nixon 2002). But what are the effects of progressive resistive
      exercise (PRE) for adults living with HIV infection?A better understanding of the
      effectiveness and safety of progressive resistive exercise will enable people
      living with HIV and their health care workers to practice effective and
      appropriate exercise prescription, thus contributing to improved overall outcomes
      for adults living with HIV infection. OBJECTIVES: To examine the safety and
      effectiveness of progressive resistive exercise interventions on weight, body
      composition, strength, immunological/virological, cardiopulmonary and
      psychological parameters in adults living with HIV infection. SEARCH STRATEGY: To
      identify studies to be included in this review, we searched the following
      databases: MEDLINE, EMBASE, CINAHL, COCHRANE, SCIENCE CITATION INDEX, PSYCHINFO,
      SOCIOLOGICAL ABSTRACTS, SSCI, ERIC, DAI and HEALTHSTAR. We also reviewed both
      published and unpublished abstracts and proceedings from major international and
      national HIV/AIDS conferences such as the Interscience 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, as well as Collaborative Review
      Group databases. Targeted journals were also hand searched for relevant articles.
      No language restriction was applied. The search strategy covered literature from
      1980-August 2003. SELECTION CRITERIA: We included studies that were randomized
      controlled trials (RCTs) comparing progressive resistive exercise interventions
      with no progressive resistive exercise or another exercise or treatment modality,
      performed at least three times per week, and lasting at least four weeks among
      adults (18 years of age or older) living with HIV/AIDS. DATA COLLECTION AND
      ANALYSIS: Data collection forms were used by reviewers to abstract data
      pertaining to study design, participants, interventions, outcomes and
      methodological quality from the studies that met inclusion criteria. Whenever
      possible, meta-analyses were conducted on outcomes using RevMan 4.2.2 computer
      software. MAIN RESULTS: Seven studies met the inclusion criteria for this
      systematic review. Meta-analysis was limited due to the following differences
      among the studies: types of exercise interventions, inclusion of co-intervention
      groups, level of exercise supervision, baseline body composition and testosterone
      levels of participants, types of outcomes assessed, and methodological quality of
      the individual studies.Main results indicated that performing progressive
      resistive exercise or a combination of progressive resistive exercise and aerobic
      exercise at least three times a week for at least four weeks appears to be safe
      and may lead to statistically and possibly clinically important increases in body
      weight and composition. Results also indicate exercise interventions may lead to
      clinically important improvements in cardiopulmonary fitness. Individual studies
      included in this review suggest that progressive resistive exercise interventions
      with or without aerobic exercise also contribute to improvements in strength and
      psychological status for adults living with HIV/AIDS. Individual studies indicate
      that progressive resistive exercise or a combination of progressive resistive and
      aerobic exercise appears to be safe for adults living with HIV/AIDS who are
      medically stable as a result of no change seen in immunological/virological
      status. These results are limited to those who continued to exercise and for whom
      there were adequate follow-up data. REVIEWERS' CONCLUSIONS: Progressive resistive
      exercise or a combination of progressive resistive exercise and aerobic exercise
      appear to be safe and may be beneficial for adults living with HIV/AIDS. These
      findings are limited by the small number of studies that could be included in
      meta-analyses, small sample sizes and variable participant withdrawal rates among
      included studies. Future research would benefit from including participants at
      various stages of HIV infection, a greater proportion of female participants, and
      participants in a variety of age groups to increase the generalizability of
      results. Furthermore, future research would benefit from studies with larger
      sample sizes that conduct an "intention-to-treat" analysis (analysis of
      participants based on the groups to which they were originally allocated) to
      better understand outcomes of participants that withdraw from exercise
      interventions.

PMID- 15495091
TI  - Single dose oral naproxen and naproxen sodium for acute postoperative pain.
AB  - BACKGROUND: Postoperative pain is often poorly managed. Treatment options include
      a range of drug therapies such as non-steroidal anti-inflammatory drugs (NSAIDs)
      of which naproxen is one. Naproxen is used to treat a variety of painful
      conditions including acute postoperative pain, and is often combined with sodium
      to improve its solubility for oral administration. Naproxen sodium 550 mg
      (equivalent to 500 mg of naproxen) is considered to be an effective dose for
      treating postoperative pain but to date no systematic review of the effectiveness
      of naproxen/naproxen sodium at different doses has been published. OBJECTIVES: To
      assess the efficacy, safety and duration of action of a single oral dose of
      naproxen or naproxen sodium for acute postoperative pain in adults. SEARCH
      STRATEGY: We searched The Cochrane Library, MEDLINE, EMBASE and the Oxford Pain
      Relief Database for relevant studies. Additional studies were identified from the
      reference list of retrieved reports. The most recent search was undertaken in
      July 2004. SELECTION CRITERIA: Included studies were randomised, double blind,
      placebo-controlled trials of a single dose of orally administered naproxen or
      naproxen sodium in adults with moderate to severe acute postoperative pain. DATA
      COLLECTION AND ANALYSIS: Pain relief or pain intensity data were extracted and
      converted into dichotomous information to give the number of patients with at
      least 50% pain relief over four to six hours. Relative risk estimates (RR) and
      the number-needed-to-treat (NNT) for at least 50% pain relief were then
      calculated. Information was sought on the percentage of patients experiencing any
      adverse event, and the number-needed-to-harm was derived. Time to remedication
      was also estimated. MAIN RESULTS: Ten trials (996 patients) met the inclusion
      criteria: nine assessed naproxen sodium; one combined the results from two small
      trials of naproxen alone. Included studies scored well for methodological
      quality. Meta-analysis of six trials (500 patients) that compared naproxen sodium
      550 mg with placebo gave a RR for at least 50% pain relief over 4 to 6 hours of
      4.2 (95% confidence interval (CI) 2.9 to 6.0) and an NNT of 2.6 (95% CI 2.2 to
      3.2). Three trials (334 patients) assessed naproxen 400 mg and naproxen sodium
      440 mg, giving a RR of 4.8 (95% CI 2.75 to 8.38). Two small studies indicated
      that naproxen 200 mg and naproxen sodium 220 mg may provide effective
      postoperative pain relief. There was no significant difference between the number
      of patients experiencing any adverse event on treatment compared with placebo.
      Weighted mean time to remedication for naproxen sodium 550 mg was 7.6 hours
      compared with 2.6 hours for placebo. REVIEWERS' CONCLUSIONS: Naproxen sodium 550
      mg, naproxen 400 mg and naproxen sodium 440 mg administered orally are effective
      analgesics for the treatment of acute postoperative pain in adults. A low
      incidence of adverse events was found but reporting was not consistent.

PMID- 15495093
TI  - Prophylactic platelet transfusion for haemorrhage after chemotherapy and stem
      cell transplantation.
AB  - BACKGROUND: Platelet transfusions are used in modern clinical practice to prevent
      and treat bleeding in thrombocytopenic patients with bone marrow failure.
      Although considerable advances have been made in platelet transfusion therapy in
      the last 30 years, some areas continue to provoke debate, especially the use of
      prophylactic platelet transfusions for the prevention of thrombocytopenic
      bleeding. OBJECTIVES: To determine the optimal use of platelet transfusion for
      the prevention of haemorrhage (prophylactic platelet transfusion) in patients
      with haematological malignancies undergoing chemotherapy or stem cell
      transplantation. SEARCH STRATEGY: Randomised controlled trials (RCTs) were
      searched for in the Cochrane Central Register of Controlled Trials (CENTRAL).
      Searching was also undertaken on the OVID versions of MEDLINE and EMBASE using an
      RCT search filter strategy. SELECTION CRITERIA: Randomised controlled trials
      involving transfusions of platelet concentrates, prepared either from individual
      units of whole blood or by apheresis, and given prophylactically to prevent
      bleeding in patients with haematological malignancies and receiving treatment
      with chemotherapy and/or stem cell transplantation. DATA COLLECTION AND ANALYSIS:
      All electronically derived citations and abstracts of papers identified by the
      review search strategy were initially screened for relevancy by one reviewer.
      Studies clearly irrelevant were excluded at this stage. The full text of all
      potentially relevant trials was then formally assessed for eligibility by two
      reviewers independently. Two reviewers completed data extraction independently.
      Missing data were requested from the original investigators, as appropriate.
      Disagreements were resolved by discussion with the other reviewers. MAIN RESULTS:
      Eight completed published trials, with a total of 390 participants in the
      intervention groups and 362 participants in the control groups, were included in
      the review for further analysis. The eight studies were classified as: * three
      trials relevant to prophylactic platelet transfusions versus therapeutic platelet
      transfusions; * three trials relevant to prophylactic platelet transfusion with
      one trigger level versus prophylactic platelet transfusion with another trigger
      level; * two trials relevant to prophylactic platelet transfusion with one dose
      schedule versus prophylactic platelet transfusion with another dose schedule. The
      few reports of controlled trials addressing prophylactic versus therapeutic
      transfusions contained small numbers of patients and were all undertaken over 25
      years ago. None of these three studies explicitly clarified whether the lack of a
      reported difference was a reflection of insufficient power in the trials. The
      findings of the meta-analyses for this group of three small studies must be
      interpreted with caution. In contrast, more contemporary trials addressed the
      question of what platelet count thresholds should apply for prophylactic
      transfusion; three identified studies broadly compared platelet transfusion
      thresholds of 10 versus 20 x 109/litre for different clinical groups of patients.
      There were no statistically significant differences between the groups with
      regards to mortality, remission rates, number of participants with severe
      bleeding events or red cell transfusion requirements. However, it was unclear
      whether the studies had sufficient power to demonstrate in combination non
      inferiority in terms of safety of the lower threshold, 10 x 109/litre.
      Insufficient randomised trials have been undertaken to make clinically relevant
      conclusions about the effect of different platelet doses. REVIEWERS' CONCLUSIONS:
      There are no reasons to change current practice but uncertainty about the
      practice of prophylactic transfusion therapy should be recognised, particularly
      in the light of concerns about the scenario that blood products, including
      platelets, could become an increasingly scarce resource in the future and for
      which adequate alternatives do not exist. Consideration should be given to
      developing adequately powered trials comparing strategies of prophylaxis versus
      therapeutic platelet transfusion.

PMID- 15495094
TI  - Interactive Health Communication Applications for people with chronic disease.
AB  - BACKGROUND: Interactive Health Communication Applications (IHCAs) are computer
      based, usually web-based health information packages for patients that combine
      information with at least one of social support, decision support, or behaviour
      change support. These are innovations in health care and their effects on health
      are uncertain. OBJECTIVES: To assess the effects of IHCAs for people with chronic
      disease. SEARCH STRATEGY: We designed a four-part search strategy. First, we
      searched electronic bibliographic databases for published work; second, we
      searched the grey literature and third, we searched for ongoing and recently
      completed clinical trials in the appropriate databases. Finally, researchers of
      included studies were contacted, and reference lists from relevant primary and
      review articles were followed up. As IHCAs require relatively new technology, the
      search commenced at 1990 where possible. SELECTION CRITERIA: Randomised
      controlled trials (RCTs) of Interactive Health Communication Applications for
      adults and children with chronic disease. DATA COLLECTION AND ANALYSIS: One
      reviewer screened abstracts. Two reviewers screened all candidate studies to
      determine eligibility, apply quality criteria, and extract data from included
      studies. Authors of included RCTs were contacted for missing data. Results of
      RCTs were pooled using a random effects model and standardised mean differences
      (SMDs) were calculated to provide net effect sizes. MAIN RESULTS: We screened
      24,757 unique citations and retrieved 958 papers for further assessment, yielding
      28 RCTs involving 4042 participants. One of these had an inadequate method of
      concealment of allocation, and sensitivity analyses were performed to determine
      the effects of including or excluding these data in the meta-analyses. Results in
      the abstract are from the meta-analyses excluding data from this study.IHCAs were
      found to have a positive effect on knowledge (SMD 0.49; 95% confidence interval
      (CI) 0.14 to 0.84) and on social support (SMD 0.47; 95% CI 0.28 to 0.66). IHCAs
      were found to have no effect on self-efficacy (SMD 0.15; 95% CI -0.13 to 0.43) or
      behavioural outcomes (SMD -0.09; 95% CI -0.49 to 0.32). IHCAs had a negative
      effect on clinical outcomes (SMD -0.32; 95% CI -0.63 to -0.02). REVIEWERS'
      CONCLUSIONS: The number and range of IHCAs is increasing rapidly; however there
      is a shortage of high quality evaluative data. Consumers who wish to increase
      their knowledge or social support amongst people with a similar problem may find
      an IHCA helpful. However, consumers whose primary aim is to achieve optimal
      clinical outcomes should not use an IHCA at present. Further research is needed
      to determine the reason for this negative effect on clinical outcomes, whether an
      optimal IHCA can achieve behaviour change and improved health outcomes, and if
      so, what are the essential features of such an IHCA, and the extent to which they
      differ according to patient group or condition.

PMID- 15495095
TI  - Additional bedtime H2-receptor antagonist for the control of nocturnal gastric
      acid breakthrough.
AB  - BACKGROUND: Nocturnal gastric acid breakthrough(NAB) is defined as intragastric
      pH<4 for more than one continuous hour overnight. Adding H2-receptor antagonists
      (H2RAs)at bedtime to high-dose proton pump inhibitors is likely to enhance
      nocturnal gastric pH control and decrease nocturnal gastric acid breakthrough.
      OBJECTIVES: To assess the effectiveness of additional bedtime H2-receptor
      antagonists in suppressing nocturnal gastric acid breakthrough and the incidence
      of adverse effects. SEARCH STRATEGY: We identified eligible trials by searching
      The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane
      Library Issue 3, 2003), MEDLINE (1966-July 2003), EMBASE (1980-July 2003) and
      CINAHL (1982-July 2003). We re-ran the search on CENTRAL (The Cochrane Library
      Issue 2, 2004), and in MEDLINE, EMBASE and CINAHL in June 2004. SELECTION
      CRITERIA: All randomized controlled trials evaluating H2-receptor antagonists for
      the control of nocturnal gastric acid breakthrough were eligible for inclusion.
      DATA COLLECTION AND ANALYSIS: We extracted data and recorded relevant information
      onto specially developed forms. One reviewer extracted data and a second reviewer
      checked data extraction. We have also double-checked data entry into RevMan. For
      binary outcomes, we expressed the impact of the intervention as relative risks,
      together with 95% confidence intervals. For scale-based outcomes, we used means
      and standard deviations to summarise the values in each group, provided the scale
      permitted sufficient values. We had intended to analyse such outcomes for the
      presence of skew, but the studies included were too limited to permit this. MAIN
      RESULTS: Two randomized crossover studies including 32 participants met the
      inclusion criteria. Because the design, dosage and duration of the treatment were
      different between the studies, it was not possible to conduct meta-analysis.
      There is no consistent conclusion between the two included studies in evaluating
      H2RAs for the control of NAB. REVIEWERS' CONCLUSIONS: We can conclude no
      implications for practice at this stage. Appropriately designed, large-scale
      randomized controlled trials with long-term follow-up are needed to determine the
      effects of additional bedtime H2RAs in suppressing nocturnal gastric acid
      breakthrough.

PMID- 15495096
TI  - Non-invasive interventions for improving well-being and quality of life in
      patients with lung cancer.
AB  - BACKGROUND: Lung cancer is one of the leading causes of death globally. Despite
      advances in treatment, outlook for the majority of patients remains grim and most
      face a pessimistic outlook accompanied by sometimes devastating effects on
      emotional and psychological health. Although chemotherapy is accepted as an
      effective treatment for advanced lung cancer, the high prevalence of treatment
      related side effects as well the symptoms of disease progression highlight the
      need for high quality palliative and supportive care to minimise symptom distress
      and to promote quality of life. OBJECTIVES: To assess the effectiveness of non
      invasive interventions delivered by healthcare professionals in improving
      symptoms, psychological functioning and quality of life in patients with lung
      cancer. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (The
      Cochrane Library Issue 4, 2003), MEDLINE (1966-March 2003), EMBASE (1974-March
      2003), CINAHL (1982-September 2002), CancerLit (1975-October 2002), PsycINFO
      (1873-March 2003), reference lists of relevant articles and contact with authors.
      SELECTION CRITERIA: Randomised or quasi-randomised clinical trials assessing the
      effects of non-invasive interventions in improving well-being and quality of life
      in patients diagnosed with lung cancer. DATA COLLECTION AND ANALYSIS: Two
      reviewers independently assessed relevant studies for inclusion. Data extraction
      and quality assessment of relevant studies was performed by one reviewer and
      checked by a second reviewer. MAIN RESULTS: Nine trials were included and
      categorised into six groups. Two trials of a nursing intervention to manage
      breathlessness showed benefit on symptom experience, performance status and
      emotional functioning. Three trials assessed structured nursing programmes and
      found positive effects on delay in clinical deterioration, dependency and symptom
      distress, and improvements in emotional functioning and satisfaction with care.
      One trial assessing counselling showed benefit on some emotional components of
      the illness but findings were not conclusive. One trial assessing an exercise
      programme, found a beneficial effect on self-empowerment. One trial of
      nutritional interventions found positive effects for increasing energy intake,
      but no improvement in quality of life. One trial of reflexology showed some
      positive, but short-lasting effects on anxiety. REVIEWERS' CONCLUSIONS: Nurse
      follow-up programmes and a nurse intervention to manage breathlessness may
      produce beneficial effects. Psychotherapeutic study indicates that counselling
      may help patients cope more effectively with emotional symptoms, but the evidence
      is not conclusive. Findings from the included studies reinforce the necessity for
      increased training and education of healthcare professionals giving in these
      interventions. More research, of higher methodological quality is needed in this
      area to explore possible underlying explanatory mechanisms.

PMID- 15495097
TI  - HMG CoA reductase inhibitors (statins) for dialysis patients.
AB  - BACKGROUND: Cardiovascular disease accounts for more than half the number of
      deaths among dialysis patients. The role of HMG CoA reductase inhibitors
      (statins) in the treatment of hyperlipidemia in dialysis patients is unclear and
      their safety has not been established. OBJECTIVES: To assess the benefits and
      harms of statins in peritoneal dialysis (PD) and hemodialysis patients (HD).
      SEARCH STRATEGY: We searched MEDLINE (1966-July 2003), EMBASE (1980-July 2003),
      the Cochrane Central Register of Controlled trials (CENTRAL, in The Cochrane
      Library - issue 2, 2004), the Cochrane Renal Group's specialized register (April
      2004) and handsearched reference lists of textbooks, articles and scientific
      proceedings. SELECTION CRITERIA: Randomized controlled trials (RCTs) and quasi
      RCTs comparing statins with placebo, no treatment or other statins in dialysis
      patients. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed
      trial quality and extracted data. Statistical analyses were performed using the
      random effects model after testing for heterogeneity. The results were expressed
      as weighted mean difference (WMD) for continuous outcomes and relative risk (RR)
      for dichotomous outcomes with 95% confidence intervals (CI). MAIN RESULTS: Six
      studies involving 357 participants were identified - three studies had both
      continuous ambulatory peritoneal dialysis (CAPD) and HD participants, two
      included only HD participants and one study only included CAPD participants.
      Studies were all of short duration and morbidity and mortality were not assessed.
      Average total cholesterol decreased significantly with statins compared to
      placebo in all dialysis patients (WMD -53.70 mg/dL (1.40 mmol/L), 95% CI -66.95
      to -40.54). Similarly, average LDL cholesterol decreased significantly with
      statins in comparison to placebo in all patients (WMD -55.40 mg/dL (1.44 mmol/L),
      95% CI -69.90 to -40.90) as did average triglycerides (-33.72 mg/dL (0.37
      mmol/L), 95% CI -54.16 to -13.28). There was a significant increase in average
      HDL cholesterol levels (WMD 4.84 mg/dL (0.13 mmol/L), 95% CI 0.28 to 9.40) with
      statins compared to placebo in HD but not in CAPD patients. One trial compared
      statins to the hypolidemic agent probucol and found no significant differences
      between the two treatment groups. REVIEWERS' CONCLUSIONS: Statins used for 12
      weeks decreased cholesterol levels in dialysis patients similar to the general
      population. Included studies were of short duration and therefore the efficacy of
      statins in decreasing the cardiovascular, cerebrovascular events and mortality
      rates is still unclear. The safety of statins needs to be addressed in the
      current ongoing clinical trials.

PMID- 15495098
TI  - Immunosuppressive treatment for idiopathic membranous nephropathy in adults with
      nephrotic syndrome.
AB  - BACKGROUND: Idiopathic membranous nephropathy (IMN) is the most common form of
      nephrotic syndrome in adults. The disease shows a benign or indolent course in
      the majority of patients, with a rate of spontaneous complete or partial
      remission of nephrotic syndrome as high as 30% or more. Despite this, 30-40% of
      patients progress toward end-stage renal failure (ESRF) within 5-15 years.
      OBJECTIVES: To assess the benefits and harms of immunosuppressive treatment for
      IMN in adults. SEARCH STRATEGY: We searched the Cochrane Renal Group Specialised
      Register (December 2003), The Cochrane Central Register of Controlled Trials
      (CENTRAL) (Cochrane Library Issue 4, 2003), MEDLINE and Pre-MEDLINE (1966 -
      December 2003), EMBASE (1980 - December 2003), reference lists of nephrology
      textbooks, review articles, prospective trial registers, relevant trials and
      abstracts from nephrology scientific meetings and the internet without language
      restriction. We also contacted principal investigators of controlled studies.
      SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing
      any immunosuppressive interventions for the treatment of IMN in adults. DATA
      COLLECTION AND ANALYSIS: Two reviewers independently assessed and extracted
      information. Information was collected on method, participants, interventions and
      outcomes (death, ESRF, proteinuria, serum creatinine, GRF, remission, adverse
      events). MAIN RESULTS: A total of 18 trials with 1025 patients were included. No
      differences were found when we combined data of all treatment categories as a
      group and compared them with placebo or no treatment. Oral glucocorticoids. No
      beneficial effect on any of the end points chosen for efficacy was observed.
      Alkylating agents showed a significant beneficial effect on complete remission
      (RR 2.37, 95%CI 1.32 to 4.25, P = 0.004) but not on partial remission (RR 1.22,
      95%CI 0.63 to 2.35, P = 0.56) or complete or partial remission (RR 1.55, 95%CI
      0.72 to 3.34, P = 0.27). Cyclophosphamide treatment resulted in significantly
      lower rate of discontinuations due to adverse events as compared to chlorambucil
      (RR 2.34, 95%CI 1.25 to 4.39, P = 0.008). There was no evidence of clinically
      relevant differences in favour of cyclosporin and there was insufficient data on
      anti-proliferative agents. REVIEWERS' CONCLUSIONS: This review failed to show any
      long-term effect of immunosuppressive treatment on patient and/or renal survival.
      There was an increased number of discontinuations due to adverse events in
      immunosuppressive treatment groups. Within the class of alkylating agents there
      is weak evidence supporting the efficacy of cyclophosphamide as compared to
      chlorambucil. On the other hand, cyclophosphamide had fewer side effects leading
      to patient withdrawal than chlorambucil.

PMID- 15495099
TI  - Dan Shen agents for acute ischaemic stroke.
AB  - BACKGROUND: Based mainly on experimental data which indicates improvement to the
      cerebral microcirculation, Dan Shen, a form of herbal medicine, is widely used in
      the treatment of acute ischaemic stroke in China. We aimed to assess the evidence
      from randomised controlled trials of their effects. OBJECTIVES: To review the
      randomised or quasi-randomised controlled trials of Dan Shen agents for acute
      ischaemic stroke. The primary objective was to determine whether Dan Shen agents
      improve functional outcome without causing undue harm in patients with acute
      ischaemic stroke. Secondary objectives were to assess the effect of Dan Shen
      agents on impairment and on quality of life. SEARCH STRATEGY: We searched the
      Cochrane Stroke Group Trials Register (last searched September 2003), the
      register of the Cochrane Complementary Field (last searched September 2003) and
      the Chinese Stroke Trials Register (last searched September 2003). In addition we
      searched the following bibliographic databases: The Cochrane Central Register of
      Controlled Trials (The Cochrane Library, Issue 4, 2002), MEDLINE (1996 to
      December 2002), EMBASE (1980 to December 2002), CINAHL (1982 to December 2002),
      AMED (1985 to December 2002) and China Biological Medicine Database (CBM-disc
      1979 to December 2002). We handsearched 10 Chinese journals, searched clinical
      trials and research databases, scanned reference lists and contacted the
      pharmaceutical company manufacturing Dan Shen. SELECTION CRITERIA: Randomised
      controlled trials or quasi-randomised controlled clinical trials comparing Dan
      Shen agents with placebo or open control (no placebo) in patients with acute
      ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two reviewers independently
      selected trials for inclusion, assessed trial quality and extracted the data.
      MAIN RESULTS: Eight potentially eligible trials were identified, of which three
      trials (304 patients) were included. Two trials were excluded and three trials
      are awaiting assessment. Numbers of deaths and dependent patients at the end of
      follow-up of at least three months were not reported in the three included
      trials. Only one trial reported adverse events. Three trials measured the outcome
      "significant improvement in neurological deficit at the end of treatment".
      Compound Dan Shen agents were associated with a significant increase in the
      number of patients with the outcome (Peto Odds Ratio (OR) 2.72, 95% Confidence
      Interval (CI) 1.10 to 6.72). No deaths were reported within the first two weeks
      of treatment or during the whole follow-up period (21 to 28 days). The trials did
      not include any assessment of quality of life. REVIEWERS' CONCLUSIONS: There were
      too few patients and outcome events to draw reliable conclusions from the present
      data. The methodological qualities of all included studies were poor. Further
      high-quality randomised controlled trials should be performed.

PMID- 15495100
TI  - Single dose oral indometacin for the treatment of acute postoperative pain.
AB  - BACKGROUND: Indometacin is a non-steroidal anti-inflammatory drug (NSAID) used
      most commonly for the treatment of inflammation and pain resulting from rheumatic
      disease (arthritis), and less commonly in postoperative pain management. When
      taken for chronic pain conditions, indometacin has been associated with a high
      incidence of adverse events. The benefits and harms of orally-administered
      indometacin for postoperative pain are not clear. OBJECTIVES: To determine the
      efficacy of a single dose of oral indometacin compared with placebo in treating
      acute postoperative pain in adults, and to analyse information relating to
      adverse events. SEARCH STRATEGY: We searched the Cochrane Central Register of
      Controlled Trials in The Cochrane Library (Issue 3, 2004), MEDLINE, EMBASE and
      the Oxford Pain Relief Database for relevant studies. Additional studies were
      sought from the reference lists of retrieved reports. SELECTION CRITERIA: Studies
      were included in the review if they were randomised, double blind, placebo
      controlled clinical trials using a single oral dose of indometacin in adults with
      acute postoperative pain. DATA COLLECTION AND ANALYSIS: Trials were assessed
      independently by two authors. Pain relief or pain intensity data were extracted
      and converted into dichotomous information to give the number of patients with at
      least 50% pain relief over four to six hours. The relative benefit for at least
      50% pain relief was calculated. MAIN RESULTS: One trial of 59 women with post
      episiotomy pain met the inclusion criteria. The dose of indometacin assessed
      against placebo was 50 mg, and the results concluded that indometacin was not
      significantly better than placebo for relieving postoperative pain at four to six
      hours. There was insufficient information to conduct further efficacy analyses or
      assess adverse events. REVIEWERS' CONCLUSIONS: Conclusions about the clinical
      efficacy of indometacin for postoperative cannot be made until more trials are
      conducted for a variety of surgical procedures, and different doses of
      indometacin are assessed.

PMID- 15495101
TI  - Arginine supplementation for prevention of necrotising enterocolitis in preterm
      infants.
AB  - BACKGROUND: Immaturity, ischemia, and disturbances in gut mucosal integrity due
      to infections or hyperosmolar feeds are some of the suspected mechanisms in the
      development of necrotising enterocolitis (NEC) in preterm infants. Decreased
      concentration of nitric oxide is proposed as one of the possible cellular
      mechanisms for NEC. Plasma arginine concentrations were found to be lower in
      infants who developed NEC. Arginine can act as a substrate for the production of
      nitric oxide in the tissues and arginine supplementation may help in preventing
      NEC. OBJECTIVES: This review examines the efficacy and safety of arginine
      supplementation in decreasing the incidence of NEC among preterm neonates. SEARCH
      STRATEGY: A literature search was performed using the following databases:
      MEDLINE (1966 - June 2004), EMBASE (1980 - June 2004), CINAHL (1982 - June 2004),
      Cochrane Controlled Trials Register (Issue 2, 2004 of Cochrane Library) and
      abstracts from the annual meetings of the Society for Pediatric Research,
      American Pediatric Society and Pediatric Academic Societies published in
      Pediatric Research (1991-2004). No language restrictions were applied. SELECTION
      CRITERIA:  STUDY DESIGN: randomized or quasi-randomized controlled trials.
      POPULATION: preterm neonates. INTERVENTION: enteral or parenteral arginine
      supplementation (in addition to what an infant may be receiving from enteral or
      parenteral source), compared to placebo or no treatment; arginine administered
      orally or parenterally for at least 7 days in order to achieve adequate plasma
      arginine levels (145 umol/l). OUTCOMES: any of the following outcomes - NEC,
      death prior to discharge, death due to NEC, surgery for NEC, duration of total
      parenteral nutrition, plasma concentrations of arginine and glutamine at baseline
      and seven days after intervention, side effects of arginine. DATA COLLECTION AND
      ANALYSIS: The methodological quality of the trials was assessed using the
      information provided in the studies and by personal communication with the
      author. Data on relevant outcomes were extracted and the effect size was
      estimated and reported as relative risk (RR), risk difference (RD) and mean
      difference (MD) as appropriate. MAIN RESULTS: Only one eligible study was
      identified. The methodological quality of the included study was good. There was
      a statistically significant reduction in the risk of developing NEC (any stage)
      in the arginine group compared with the placebo group (RR 0.24 [95% CI 0.10,
      0.61], RD -0.21 [95% CI -0.32, -0.09]). No significant side effects directly
      attributable to arginine were observed. REVIEWERS' CONCLUSIONS: The data are
      insufficient at present to support a practice recommendation. A multicentre
      randomized controlled study of arginine supplementation in preterm neonates is
      needed, focusing on the incidence of NEC, particularly stage 2 or 3.

PMID- 15495102
TI  - Positive end-expiratory pressure for resuscitation of newborn infants at birth.
AB  - BACKGROUND: Effective ventilation is the key to successful neonatal
      resuscitation. Positive pressure ventilation is initiated with manual ventilation
      devices which may or not deliver positive end-expiratory pressure (PEEP). PEEP is
      known to have beneficial effects in preterm animal models and its use is
      ubiquitous in mechanical ventilation in neonatal intensive care. OBJECTIVES: To
      determine whether the use of PEEP during positive pressure ventilation at
      neonatal resuscitation reduces mortality or morbidity. SEARCH STRATEGY: The
      standard search strategy of the Cochrane Neonatal Review Group was used. Pub Med
      (1966 to May 2004) was searched using the MeSH headings Infant, Newborn,
      Resuscitation, Positive Pressure Respiration and the text words Positive End
      Expiratory Pressure or PEEP. The Cochrane Central Register of Controlled Trials
      (The Cochrane Library, Issue 1, 2004) was searched using text words Newborn and
      Resuscitation. No language restrictions were applied. The abstracts of the
      Society for Pediatric Research and the European Society for Pediatric Research,
      were searched from 1995-May 2004. Abstracts were also searched in
      Anaesthesiology, Canadian Journal of Anaesthesia, British Journal of Anaesthesia,
      Anaesthesia and Intensive Care and Anaesthesia and Analgesia. SELECTION CRITERIA:
      Randomised and quasi-randomised controlled trials comparing ventilation devices
      providing PEEP with those not providing PEEP in the resuscitation of infants at
      birth. DATA COLLECTION AND ANALYSIS: Assessment of methodology regarding blinding
      of randomisation, intervention and outcome measurements as well as completeness
      of follow-up was planned. We planned to evaluate the treatment effect using a
      fixed effects model using relative risk (RR), relative risk reduction, risk
      difference (RD) and number needed to treat (NNT) for categorical data and using
      mean, standard deviation and weighted mean difference (WMD) for continuous data.
      We planned an evaluation of heterogeneity to help determine the suitability of
      pooling results. MAIN RESULTS: No studies were found meeting the criteria for
      inclusion in this review. REVIEWERS' CONCLUSIONS: There is insufficient evidence
      to determine the efficacy and safety of PEEP during positive pressure ventilation
      at neonatal resuscitation. Randomised clinical trials comparing positive pressure
      ventilation with and without PEEP at neonatal resuscitation are warranted.

PMID- 15495103
TI  - Treatment for avascular necrosis of bone in people with sickle cell disease.
AB  - BACKGROUND: Avascular necrosis of bone is a frequent and severe complication of
      sickle cell disease and its treatment is not standardised. It is therefore
      important to gather evidence about the safety and effectiveness of different
      interventions. OBJECTIVES: To determine the impact of surgery compared to non
      surgical management on both the short- and the long-term outcomes (efficacy,
      safety, and adverse events) for people with sickle cell disease-related avascular
      necrosis. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic
      Disorders Group trials register, which comprises references identified from
      comprehensive electronic database searches and handsearches of relevant journals
      and abstract books of conference proceedings. Additional randomized controlled
      trials were sought from the reference lists of the trials found and reviews
      identified by the search strategy. Date of the most recent search: April 2004.
      SELECTION CRITERIA: All randomized or quasi-randomized controlled trials
      (published or unpublished). DATA COLLECTION AND ANALYSIS: One ongoing clinical
      trial has been identified but no data are available for inclusion in the review.
      MAIN RESULTS: Five trials were identified by the searches. Four trials were not
      eligible for inclusion and one is an ongoing clinical trial. REVIEWERS'
      CONCLUSIONS: We were unable to find any evidence from completed randomized
      controlled trials assessing treatments for avascular necrosis in people with
      sickle cell disease. We await the results of an ongoing clinical trial to assess
      the benefits and risks of a surgical approach compared to a non-surgical approach
      as a means of improving survival and quality of life for people with sickle cell
      disease-related avascular necrosis of bone.

PMID- 15495104
TI  - Betamimetics for inhibiting preterm labour.
AB  - BACKGROUND: Preterm birth is a major contributor to perinatal mortality and
      morbidity worldwide. Tocolytic agents are drugs used to inhibit uterine
      contractions. The most widely used tocolytic agents are betamimetics especially
      in resource-poor countries. OBJECTIVES: To assess the effects of betamimetics
      given to women with preterm labour. SEARCH STRATEGY: We searched the Cochrane
      Pregnancy and Childbirth Group trials register (May 2003) without language
      restrictions. SELECTION CRITERIA: Randomised controlled trials of betamimetics,
      administered by any route or any dose, in the treatment of women in preterm
      labour where betamimetics are compared with other betamimetics, placebo or no
      treatment. DATA COLLECTION AND ANALYSIS: Two reviewers evaluated independently
      methodological quality and extracted the data. We sought additional information
      to enable assessment of methodology and conduct intention-to-treat analyses. We
      present the results using the relative risk for categorical data and the weighted
      mean difference for continuous data. MAIN RESULTS: Eleven randomised controlled
      trials, involving 1332 women, compared betamimetics with placebo. Betamimetics
      decreased the number of women in preterm labour giving birth within 48 hours
      (relative risk (RR) 0.63; 95% confidence interval (CI) 0.53 to 0.75) but there
      was no decrease in the number of births within seven days after carrying out a
      sensitivity analysis of studies with adequate allocation of concealment. No
      benefit was demonstrated for betamimetics on perinatal death (RR 0.84; 95% CI
      0.46 to 1.55, 7 trials, n = 1332), or neonatal death (RR 1.00; 95% CI 0.48 to
      2.09, 5 trials, n = 1174). No significant effect was demonstrated for respiratory
      distress syndrome (RR 0.87; 95% CI 0.71 to 1.08, 8 trials, n = 1239). A few
      trials reported the following outcomes, with no difference detected: cerebral
      palsy, infant death and necrotizing enterocolitis. Betamimetics were
      significantly associated with the following: withdrawal from treatment due to
      adverse effects; chest pain; dyspnoea; tachycardia; palpitation; tremor;
      headaches; hypokalemia; hyperglycemia; nausea/vomiting; and nasal stuffiness; and
      fetal tachycardia. Other betamimetics were compared with ritodrine in five trials
      (n = 948). Trials were small, varied and of insufficient quality to delineate any
      consistent patterns of effect. REVIEWERS' CONCLUSIONS: Betamimetics help to delay
      delivery for women transferred to tertiary care or completed a course of
      antenatal corticosteroids. However, multiple adverse effects must be considered.
      The data are too few to support the use of any particular betamimetics.

PMID- 15495106
TI  - Chlorproguanil-dapsone for treating uncomplicated malaria.
AB  - BACKGROUND: In Africa, malaria is often resistant to chloroquine and sulfadoxine
      pyrimethamine. Chlorproguanil-dapsone is a potential alternative. OBJECTIVES: To
      compare chlorproguanil-dapsone with other antimalarial drugs for treating
      uncomplicated falciparum malaria. SEARCH STRATEGY: We searched the Cochrane
      Infectious Diseases Group Specialized Register (May 2004), CENTRAL (The Cochrane
      Library Issue 2, 2004), MEDLINE (1966 to May 2004), EMBASE (1988 to May 2004),
      LILACS (May 2004), Biosis Previews (1985 to May 2004), conference proceedings,
      and reference lists, and contacted researchers working in this field. SELECTION
      CRITERIA: Randomized and quasi-randomized controlled trials comparing
      chlorproguanil-dapsone to other antimalarial drugs. DATA COLLECTION AND ANALYSIS:
      Two reviewers independently applied the inclusion criteria, extracted data, and
      assessed methodological quality. We calculated the relative risk (RR) for
      dichotomous data and weighted mean difference for continuous data, and presented
      them with 95% confidence intervals (CI). MAIN RESULTS: Six trials (n = 3352) met
      the inclusion criteria. Chlorproguanil-dapsone (with 1.2 mg chlorproguanil) as a
      single dose had fewer treatment failures than chloroquine (1 trial), but more
      treatment failures and people with parasitaemia at day 28 than sulfadoxine
      pyrimethamine (3 trials). Two trials compared the three-dose chlorproguanil
      dapsone (with 2 mg chlorproguanil) regimen with sulfadoxine-pyrimethamine in new
      attendees. There were fewer treatment failures with chlorproguanil-dapsone by day
      7 (RR 0.30, CI 0.19 to 0.49; n = 827, 1 trial) and day 14 (RR 0.36, CI 0.24 to
      0.53; n = 1709, 1 trial). Neither trial reported total failures by day 28. A
      further trial was carried out in participants selected because they had
      previously failed sulfadoxine-pyrimethamine. Adverse event reporting was
      inconsistent between trials, but chlorproguanil-dapsone was associated with more
      adverse events leading to discontinuation of treatment compared with sulfadoxine
      pyrimethamine (RR 4.54, CI 1.74 to 11.82; n = 829, 1 trial). It was also
      associated with more red blood cell disorders (RR 2.86, CI 1.33 to 6.13; n =
      1850, 1 trial). REVIEWERS' CONCLUSIONS: There are insufficient data about the
      effects of the current standard chlorproguanil-dapsone regimen (three-dose, 2 mg
      chlorproguanil). Randomized controlled trials that follow up to day 28, record
      adverse events, and use an intention-to-treat analysis are required to inform any
      policy decisions.

PMID- 15495107
TI  - Intramuscular arteether for treating severe malaria.
AB  - BACKGROUND: Quinine and artemisinin drugs are used in severe malaria, but quinine
      resistance is increasing. Arteether is a recently developed artemisinin
      derivative that is oil soluble, has a long elimination half life, and is more
      stable than other derivatives. OBJECTIVES: To compare intramuscular arteether
      with other antimalarial drugs to treat severe malaria. 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 (1980 to August 2004), U.S. National Library of Medicine (NLM)
      Gateway (1953 to 1965), Web Science Citation (1981 to August 2004), LILACS
      (August 2004), Google search engine (August 2004), conference proceedings, and
      reference lists. We also contacted researchers, organizations, and pharmaceutical
      companies to help identify trials. SELECTION CRITERIA: Randomized and quasi
      randomized controlled trials of intramuscular arteether in adults and children
      with severe malaria. DATA COLLECTION AND ANALYSIS: We independently assessed the
      methodological quality of the trials and extracted data, and analysed data using
      Review Manager 4.2. MAIN RESULTS: Two small trials (n = 194) met the inclusion
      criteria. Both trials compared arteether with quinine in children with cerebral
      malaria and reported on similar outcomes. There was no statistically significant
      difference in the number of deaths (relative risk 0.75, 95% confidence interval
      0.43 to 1.30; n = 194, 2 trials), neurological complications (relative risk 1.18,
      95% confidence interval 0.31 to 4.46; n = 58, 1 trial), or other outcomes
      including time to regain consciousness, parasite clearance time, and fever
      clearance time. The meta-analyses lack statistical power to detect important
      differences. REVIEWERS' CONCLUSIONS: More trials with a larger number of
      participants are needed before a firm conclusion about the efficacy and safety of
      arteether can be reached.

PMID- 15495105
TI  - Interventions to improve adherence to lipid lowering medication.
AB  - BACKGROUND: Lipid lowering drugs are still widely underused, despite compelling
      evidence about their effectiveness in the treatment and prevention of
      cardiovascular disease. Poor patient adherence to medication regimen is a major
      factor in the lack of success in treating hyperlipidaemia. In this review we
      focus on interventions, which encourage patients at risk of heart disease or
      stroke to take lipid lowering medication regularly. OBJECTIVES: To assess the
      effect of interventions aiming at improved adherence to lipid lowering drugs,
      focusing on measures of adherence and clinical outcomes. SEARCH STRATEGY: We
      searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE,
      EMBASE, PsycInfo and CINAHL. Date of most recent search was in February 2003. No
      language restrictions were applied. SELECTION CRITERIA: Randomised controlled
      trials of adherence-enhancing interventions to lipid lowering medication in
      adults for both primary and secondary prevention of cardiovascular disease in an
      ambulatory setting. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data
      independently and assessed studies according to criteria outlined by the Cochrane
      Reviewers' Handbook. MAIN RESULTS: The eight studies found contained data on 5943
      patients. Interventions could be stratified into four categories : 1.
      simplification of drug regimen, 2. patient information/education, 3. intensified
      patient care such as reminding and 4. complex behavioural interventions such as
      group sessions. Change in adherence ranged from -3% to 25% (decrease in adherence
      by 3% to increase in adherence by 25%). Three studies reported significantly
      improved adherence through simplification of drug regimen (category 1), improved
      patient information/education (category 2) and reminding (category 3). The fact
      that the successful interventions were evenly spread across the categories, does
      not suggest any advantage of one particular type of intervention. The
      methodological and analytical quality was generally low and results have to be
      considered with caution. Combining data was not appropriate due to the
      substantial heterogeneity between included randomised controlled trials (RCTs).
      REVIEWERS' CONCLUSIONS: At this stage, no specific intervention aimed at
      improving adherence to lipid lowering drugs can be recommended. The lack of a
      gold standard method of measuring adherence is one major barrier in adherence
      research. More reliable data might be achieved by newer methods of measurement,
      more consistency in adherence assessment and longer duration of follow-up.
      Increased patient-centredness with emphasis on the patient's perspective and
      shared-decision-making might lead to more conclusive answers when searching for
      tools to encourage patients to take lipid lowering medication.

PMID- 15495108
TI  - Delayed antibiotics for symptoms and complications of respiratory infections.
AB  - BACKGROUND: The use of antibiotics for upper respiratory tract infections is
      controversial. Any benefits have to be weighed against common adverse reactions
      (including rash, abdominal pain, diarrhoea and vomiting), cost and antibacterial
      resistance. There has been interest in ways to reduce antibiotic prescribing for
      acute respiratory infections. One is delaying the use of prescribed antibiotics
      by more than 48 hours for acute upper respiratory tract infections. Such methods
      have been shown to reduce prescribing. This review asks what effect this practice
      has on the clinical course of the illness. OBJECTIVES: To evaluate the clinical
      effect of delayed antibiotic use in acute upper respiratory tract infections
      compared to immediate use of antibiotics SEARCH STRATEGY: The following
      electronic databases were searched: the Cochrane Central Register of Controlled
      Trials (CENTRAL) (The Cochrane Library Issue 1, 2004) which includes the Acute
      Respiratory Infection Groups' specialised register; MEDLINE (January 1966 to
      January Week 1 2004), EMBASE (1990 to September 2003) and Current Contents (1998
      to 2003). The search was carried out by an expert librarian. Abstracts of
      identified articles were used to determine which studies were trials. SELECTION
      CRITERIA: Randomised controlled trials involving patients of all ages defined as
      having acute otitis media, acute pharyngitis, sore throat, common cold, a viral
      upper respiratory tract infection, acute sinusitis, and acute bronchitis were
      included in which delayed antibiotics are compared to antibiotics used
      immediately. Delayed antibiotic use was defined as the use of or advice to use
      antibiotics more than 48 hours after the initial consultation. 'Immediate
      antibiotic use' was defined as the immediate use of oral antibiotics given at the
      initial consultation. Clinical outcomes measured included: the presence or
      absence of fever, cough, pain, duration and severity of illness, complications of
      the disease, adverse effects from the antibiotics. Trial quality was assessed
      independently by two reviewers who were blinded to the author, journal and
      results of each study. DATA COLLECTION AND ANALYSIS: Data was collected by two
      reviewers who were blinded to the author and journal. Data were analysed and
      reported using RevMan. MAIN RESULTS: Seven trials were eligible on the basis of
      design and all reported patient-centred outcomes. Methodological quality of
      included trials was generally high. There was no difference between immediate and
      delayed antibiotic groups for symptoms on day one and day seven. For most symptom
      measures there was no significant difference between the immediate and delayed
      antibiotic groups. Missing data and marked heterogeneity between study outcomes
      prevented pooling of results as a meta-analysis. Three studies out of six
      reporting fever, all involving patients with sore throat, indicated that there
      was more fever in the delayed antibiotic group. The remaining three studies
      showed no difference. There was no significant symptom difference for patients
      with cough or the common cold between the two intervention groups. Pain and
      malaise severity scores at day three significantly favoured the immediate
      antibiotic group in children with acute otitis media (Little 2001). In this study
      by Little 2001 of children with otitis media proxies for other malaise related
      outcomes were reported, including 'last day of crying' which favoured the
      immediate antibiotic group by approximately 16 hours (0.69 days; 95% CI 0.31 to
      1.07). In the same study, just over half a spoon of paracetamol a day less was
      used in the immediate antibiotic group (0.59; 95% CI 0.25 to 0.93). There was no
      significant difference between the intervention groups for the adverse outcome of
      rash. Two studies reported the outcome of vomiting which was reduced in the
      immediate antibiotic group in children with suspected streptococcal pharyngitis
      in El-Daher 1991 but there was no difference in children with sore throat in
      Little 1997. Diarrhoea was reported by three studies of which two showed no
      difference Little 1997; Arroll 2002a while Little 2001 reported less diarrhoea in
      the delayed antibiotic group in children with otitis media. REVIEWERS'
      CONCLUSIONS: When considering treatment options for upper respiratory tract
      infections, the option of delayed antibiotics has been used in an attempt to
      reduce the use of antibiotic prescriptions. This review shows that for all
      symptom scores the evidence varies between trials. Most symptom outcomes show no
      difference between immediate and delayed antibiotic groups. Three of the six
      studies, all involving patients with sore throat, indicated that patients in the
      delayed antibiotic group had significantly more fever that their counterparts in
      the immediate antibiotic group. The other three showed no difference for the
      outcome of fever. There is evidence indicating that for children with otitis
      media, pain and malaise scores are worse in the delayed antibiotic group compared
      to the immediate antibiotic group. This price must be weighed up against the
      benefits of reduced antibiotic prescribing. Future randomised controlled trials
      of delaying antibiotics as an intervention should fully report symptoms as well
      as changes of prescription rates.

PMID- 15495109
TI  - Oral appliances for obstructive sleep apnoea.
AB  - BACKGROUND: Obstructive sleep apnoea-hypopnoea is a syndrome characterised by
      recurrent episodes of partial or complete upper airway obstruction during sleep
      that are usually terminated by an arousal. Nasal continuous positive airway
      pressure is the primary treatment for obstructive sleep apnoea-hypopnoea, but
      many patients are unable or unwilling to comply with this treatment. Oral
      appliances are an alternative treatment for sleep apnoea. OBJECTIVES: The
      objective was to review the effects of oral appliance in the treatment of sleep
      apnoea in adults. SEARCH STRATEGY: We searched the Cochrane Airways Group Sleep
      Apnoea RCT Register. Searches were current as of June 2004. Reference lists of
      articles were also searched. SELECTION CRITERIA: Randomised trials comparing oral
      appliance with control or other treatments in adults with sleep apnoea. DATA
      COLLECTION AND ANALYSIS: Trial quality was assessed and two reviewers extracted
      data independently. Study authors were contacted for missing information. MAIN
      RESULTS: Thirteen trials involving 553 participants were included. All the
      studies had some shortcomings, such as small sample size, under-reporting of
      methods and data, and lack of blinding. Oral appliances versus control appliances
      (five studies): Oral appliances reduced daytime sleepiness in two crossover
      trials (WMD -1.81 [95%CI: -2.72, -0.90]), and improved apnoea-hypopnoea index
      (AHI) (-13.17 [-18.53 to -7.80] parallel group data - four studies). Oral
      appliances versus CPAP (seven studies): Oral appliances were less effective than
      continuous positive pressure in reducing apnoea-hypopnoea index (WMD 13 [95% CI:
      7.63, 18.36], parallel studies - two trials; WMD 6.96 [4.82, 9.10] cross-over
      studies - six trials). However, no significant difference was observed on symptom
      scores. Nasal continuous positive pressure was more effective at improving
      minimum arterial oxygen saturation during sleep compared with oral appliance. In
      two small crossover studies, participants preferred oral appliance therapy to
      continuous positive airways pressure. Oral appliances versus surgery (one study):
      Symptoms of daytime sleepiness were initially lower with surgery, but this
      difference disappeared at 12 months. AHI did not differ significantly initially,
      but did so after 12 months in favour of OA. REVIEWERS' CONCLUSIONS: There is some
      evidence suggesting that oral appliance improves subjective sleepiness and sleep
      disordered breathing compared with a control. Nasal continuous positive airways
      pressure appears to be more effective in improving sleep disordered breathing
      than oral appliance. Until there is more definitive evidence on the effectiveness
      of oral appliances, it would appear to be appropriate to restrict oral appliance
      therapy to patients with sleep apnoea who are unwilling or unable to comply with
      continuous positive airways pressure therapy.

PMID- 15495110
TI  - Spinal injuries centres (SICs) for acute traumatic spinal cord injury.
AB  - BACKGROUND: The majority of complications in traumatic spinal cord injury (SCI)
      can occur in the first 24 hours and it has been suggested that spinal injury
      centres (SICs) may influence the pre-transfer care of people with SCI. The
      specialist SIC concept has been adopted in a number of high-income countries.
      However, even in such countries, a potentially significant number of people with
      SCI do not have the opportunity to access this system and are managed in a non
      specialist environment. OBJECTIVES: To answer the question: does immediate
      referral to an SIC result in a better outcome than delayed referral? SEARCH
      STRATEGY: The following databases were searched: AMED, CCTR, CINAHL, DARE,
      EMBASE, HEED, HMIC, MEDLINE, NRR, NHS EED, and PsycLIT. Searches were updated in
      May 2003 and included the Cochrane Injuries Group Specialist Register. The
      reference lists of retrieved articles were checked. SELECTION CRITERIA:
      Randomised controlled trials and controlled trials that compared immediate
      referral to an SIC with delayed referral in patients with a traumatic SCI. DATA
      COLLECTION AND ANALYSIS: Two reviewers independently selected studies. One
      reviewer was to have assessed the quality of the studies and extracted data. MAIN
      RESULTS: No randomised controlled trials or controlled trials were identified
      that compared immediate referral to an SIC with delayed referral in patients with
      a traumatic SCI. All of the studies identified were retrospective observational
      studies and of poor quality. REVIEWERS' CONCLUSIONS: The current evidence does
      not enable conclusions to be drawn about the benefits or disadvantages of
      immediate referral versus late referral to SICs. Well-designed, prospective
      experimental studies with appropriately matched controls are needed.

PMID- 15495111
TI  - Discontinuation of epidural analgesia late in labour for reducing the adverse
      delivery outcomes associated with epidural analgesia.
AB  - BACKGROUND: Although epidural analgesia provides the most effective labour
      analgesia, it is associated with some adverse obstetric consequences, including
      an increased risk of instrumental delivery. Many centres discontinue epidural
      analgesia late in labour to improve a woman's ability to push and reduce the rate
      of instrumental delivery. OBJECTIVES: To assess the impact of discontinuing
      epidural analgesia late in labour on: i) rates of instrumental deliveries and
      other delivery outcomes; and ii) analgesia and satisfaction with labour care.
      SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials
      register (1 September 2003). SELECTION CRITERIA: Randomised controlled trials of
      epidurals discontinued late in labour compared with continuation of the same
      epidural protocol until birth, in women who receive an epidural for analgesia in
      the first stage of labour. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently assessed study eligibility and quality and extracted the data. We
      analysed categorical data using relative risk (RR), and continuous data using
      weighted mean difference. MAIN RESULTS: We identified six studies, of which five
      were included (462 participants). Three of these were high quality studies whilst
      the other two were judged to be of lower quality because placebo was not used and
      the method of randomisation not described. All studies used different epidural
      analgesia protocols (type of drug, dosage or method of administration). Overall,
      the reduction in instrumental delivery rate was not statistically significant
      (23% versus 28%, RR 0.84, 95% confidence interval (CI) 0.61 to 1.15) nor was
      there any statistically significant difference in rates of other delivery
      outcomes. The only statistically significant result was an increase in inadequate
      pain relief when the epidural was stopped (22% versus 6%, RR 3.68, 95% CI 1.99 to
      6.80). REVIEWERS' CONCLUSIONS: There is insufficient evidence to support the
      hypothesis that discontinuing epidural analgesia late in labour reduces the rate
      of instrumental delivery. There is evidence that it increases the rate of
      inadequate pain relief in the second stage of labour. The practice of
      discontinuing epidurals is widespread and the size of the reduction in
      instrumental delivery rate could be clinically important; therefore, we recommend
      a larger study than those included in this review be undertaken to determine
      whether this effect is real or has occurred by chance, and to provide stronger
      evidence about the safety aspects.

PMID- 15495112
TI  - Low glycaemic index diets for coronary heart disease.
AB  - BACKGROUND: The glycaemic index (GI) is a physiological measure of the ability of
      a carbohydrate to affect blood glucose. Interest is growing in the low GI
      carbohydrate concept for the clinical management of people at risk of, or with
      established coronary heart disease. There is a need to review the current
      evidence from controlled trials in this area. OBJECTIVES: The primary objective
      is to review the current evidence from RCTs that assess the relationship between
      the consumption of low glycaemic index diets and the effects on coronary heart
      disease and on risk factors for coronary heart disease. SEARCH STRATEGY: We
      searched CENTRAL (Issue 4, 2003), MEDLINE (1966 to 2003), EMBASE (1980 to 2003)
      and CINAHL (1982 to 2003). We also contacted experts in the field. SELECTION
      CRITERIA: We selected randomised controlled trials that assessed the effects of
      low glycaemic index diets, over a minimum of 4 weeks, on coronary heart disease
      (CHD) and risk factors. Participants included were adults who carry at least one
      major risk factor for coronary heart disease such as abnormal lipids, diabetes or
      being overweight. DATA COLLECTION AND ANALYSIS: Two of our research team
      independently assessed trial quality and extracted data. Authors of the included
      studies were contacted for additional information when this was appropriate. MAIN
      RESULTS: Fifteen randomised controlled trials met the inclusion criteria. No
      studies found reported the effect of low glycaemic index diets on CHD mortality
      or CHD events and morbidity. All fifteen included studies report the effect of
      low glycaemic index diets on major risk factors for CHD. Meta-analysis detected
      limited and weak evidence of a relationship between low glycaemic index diets and
      slightly lower total cholesterol, compared with higher glycaemic index diets.
      There is also limited and weak evidence of a small reduction in HbA1c after 12
      weeks on low glycaemic index diets but not at 4 to 5 weeks. There is no evidence
      that low glycaemic index diets have an effect on LDL cholesterol or HDL
      cholesterol, triglycerides, fasting glucose or fasting insulin levels. REVIEWERS'
      CONCLUSIONS: The evidence from randomised controlled trials showing that low
      glycaemic index diets reduces coronary heart disease and CHD risk factors is
      weak. Many of the trials identified were short-term, of poor quality and
      conducted on small sample sizes. There is a need for well designed, adequately
      powered, randomised controlled studies, of greater than 12 weeks duration to
      assess the effects of low glycaemic index diets for CHD.

PMID- 15495113
TI  - Pharmacologic therapies for adults with acute lung injury and acute respiratory
      distress syndrome.
AB  - BACKGROUND: Multiple pharmacologic treatments have been studied for acute lung
      injury (ALI) and acute respiratory distress syndrome (ARDS). OBJECTIVES: Our
      objective was to determine the effects of pharmacologic treatments on clinical
      outcomes in adults with ALI or ARDS. SEARCH STRATEGY: We searched OVID versions
      of CENTRAL (The Cochrane Library Issue 3, 2003), MEDLINE (1966 to week 2, January
      2004), EMBASE (1980 to week 4, 2004), CINAHL (1982 to week 2, January 2004), and
      HEALTHSTAR (1995 to December 2003); proceedings from four conferences (1994 to
      2003); and bibliographies of review articles and included studies. SELECTION
      CRITERIA: Randomized controlled trials of pharmacologic treatments compared to no
      therapy or placebo for established ALI or ARDS in adults admitted to an intensive
      care unit, with measurement of early mortality (primary outcome), late mortality,
      duration of mechanical ventilation, ventilator-free days to day 28, or adverse
      events. We excluded trials of nitric oxide, partial liquid ventilation, fluid and
      nutritional interventions, oxygen, and trials in other populations reporting
      outcomes in subgroups of patients with ALI or ARDS. DATA COLLECTION AND ANALYSIS:
      Two reviewers independently screened titles and abstracts, rated studies for
      inclusion, extracted data and assessed methodologic quality of included studies.
      Disagreements were resolved by consensus in consultation with a third reviewer.
      For each pharmacologic therapy, we quantitatively pooled the results of studies
      using random effects models where permitted by the available data. We contacted
      study authors when clarification of the primary outcome was required. MAIN
      RESULTS: Thirty three trials randomizing 3272 patients met our inclusion
      criteria. Pooling of results showed no effect on early mortality of prostaglandin
      E1 (seven trials randomizing 697 patients; relative risk [RR] 0.95, 95%
      confidence interval [CI] 0.77 to 1.17), N-acetylcysteine (five trials randomizing
      239 patients; RR 0.89, 95% CI 0.65 to 1.21), early high-dose corticosteroids (two
      trials randomizing 187 patients; RR 1.12, 95% CI 0.72 to 1.74), or surfactant
      (nine trials randomizing 1441 patients; RR 0.93, 95% CI 0.77 to 1.12). Two
      interventions were beneficial in single small trials; corticosteroids given for
      late phase ARDS reduced hospital mortality (24 patients; RR 0.20, 95% CI 0.05 to
      0.81), and pentoxifylline reduced one-month mortality (RR 0.67, 95% CI 0.47 to
      0.95) in 30 patients with metastatic cancer and ARDS. Individual trials of nine
      additional interventions failed to show a beneficial effect on prespecified
      outcomes. REVIEWERS' CONCLUSIONS: Effective pharmacotherapy for ALI and ARDS is
      extremely limited, with insufficient evidence to support any specific
      intervention.

PMID- 15495114
TI  - Antibiotic regimens for suspected early neonatal sepsis.
AB  - BACKGROUND: Early acquired infection may cause severe illness or death in the
      neonatal period. Prompt treatment with antibiotics has shown to reduce mortality.
      It is not clear which antibiotic regimen is suitable for treatment of presumed
      early neonatal sepsis. OBJECTIVES: To compare effectiveness and adverse effects
      of antibiotic regimens for treatment of presumed early neonatal sepsis. SEARCH
      STRATEGY: The Cochrane Central Register of Controlled Trials (CENTRAL, The
      Cochrane Library, Issue 2, 2003), MEDLINE (1966 to August 2003), EMBASE (1980 to
      September 2003) and ZETOC (1993 to August 2003) databases were searched for
      possible studies. Pharmaceutical companies were contacted for any unpublished
      data. SELECTION CRITERIA: Randomised and quasi-randomised controlled studies
      comparing antibiotic regimens for the treatment of early neonatal sepsis (both
      monotherapies and combination therapies). DATA COLLECTION AND ANALYSIS: Both
      reviewers screened abstracts and full reports against the inclusion criteria,
      appraised the quality of and extracted data from papers. For dichotomous
      outcomes, treatment effect was expressed as relative risk with 95% confidence
      interval. Meta-analysis was performed using a fixed effect model. MAIN RESULTS:
      Two small studies had compared monotherapy with combination therapy. There was no
      significant difference in mortality, treatment failure or bacteriological
      resistance. REVIEWERS' CONCLUSIONS: There is no evidence from randomised trials
      to suggest that any antibiotic regimen may be better than any other in the
      treatment of presumed early neonatal sepsis. More studies are needed to resolve
      this issue.

PMID- 15495116
TI  - Carnitine supplementation for preterm infants with recurrent apnea.
AB  - BACKGROUND: Apnea of prematurity is a common problem in preterm infants in the
      neonatal intensive care setting (NICU), often delaying their discharge home or
      transfer to a step down unit. Premature infants are at increased risk of
      carnitine deficiency. Carnitine supplementation has been used for both prevention
      and treatment of apnea. OBJECTIVES: To determine whether treatment with carnitine
      will reduce the frequency of apnea, the duration of ventilation and the duration
      of hospital stay in preterm infants with recurrent apnea. SEARCH STRATEGY:
      Computerised searches were carried out by two reviewers independently. Searches
      were made of MEDLINE (1966 to May 2004), EMBASE (1980 to May 2004), CINAHL (1982
      2004 June 2004,1st week), the Cochrane Central Register of Controlled Trials
      (CENTRAL, The Cochrane Library, Issue 2, 2004), abstracts of annual meetings of
      the Society for Pediatric Research (1995-2004), and contacts were made with the
      subject experts. SELECTION CRITERIA: Only randomized or quasi-randomized
      treatment trials of preterm infants with a diagnosis of recurrent apnea of
      prematurity were considered. Trials were included if they involved treatment with
      carnitine compared to placebo or no treatment, and measured at least one of the
      following outcomes: failure of resolution of apneas, the duration of ventilation
      and the duration of hospital stay. DATA COLLECTION AND ANALYSIS: Two reviewers
      evaluated the papers for inclusion criteria and quality. Corresponding authors
      were contacted for further information where needed. MAIN RESULTS: No eligible
      trials were identified. REVIEWERS' CONCLUSIONS: Despite the plausible rationale
      for the treatment of apnea of prematurity with carnitine, there are insufficient
      data to support its use for this indication. Further studies are needed to
      determine the role of this treatment in clinical practice.

PMID- 15495115
TI  - Intraventricular antibiotics for bacterial meningitis in neonates.
AB  - BACKGROUND: Neonatal meningitis may be caused by bacteria, especially gram
      negative bacteria, which are difficult to eradicate from the cerebrospinal fluid
      (CSF) using safe doses of antibiotics. In theory, intraventricular administration
      of antibiotics would produce higher antibiotic concentrations in the CSF than
      intravenous administration alone, and eliminate the bacteria more quickly.
      However, ventricular taps may cause harm. OBJECTIVES: To assess the effectiveness
      and safety of intraventricular antibiotics (with or without intravenous
      antibiotics) in neonates with meningitis (with or without ventriculitis) as
      compared to treatment with intravenous antibiotics alone. SEARCH STRATEGY:
      MEDLINE, EMBASE, The Cochrane Library, Issue 2, 2004, Science Citation Index, and
      the Oxford Database of Perinatal Trials were searched in June 2004. Pediatric
      Research (abstracts of proceedings) were searched (1990 - April 2004) as were
      reference lists of identified trials and personal files. No language restrictions
      were applied. SELECTION CRITERIA: Selection criteria for study inclusion were:
      Randomized or quasi-randomized controlled trials in which intraventricular
      antibiotics with or without intravenous antibiotics were compared with
      intravenous antibiotics alone in neonates (< 28 days old) with meningitis. One of
      the following outcomes was required to be reported: mortality during initial
      hospitalization, neonatal and/or infant mortality, neurodevelopmental outcome,
      duration of hospitalization, duration of culture positivity of CSF and side
      effects. DATA COLLECTION AND ANALYSIS: All reviewers abstracted information for
      outcomes reported and one reviewer checked for discrepancies and entered data
      into RevMan 4.2. Relative risk (RR), risk difference (RD), number needed to treat
      (NNT) or number needed to harm (NNH), and mean difference (MD), using the fixed
      effects model are reported with 95% confidence intervals (CI). The fixed effect
      model was used for meta-analysis. MAIN RESULTS: One study was included in the
      review. This study assessed the effect of intraventricular gentamicin in a mixed
      population of neonates (69%) and older infants (31%) with gram negative
      meningitis and ventriculitis. Mortality was statistically significantly higher in
      the group that received intraventricular gentamicin in addition to intravenous
      antibiotics compared to the group receiving intravenous antibiotics alone [RR
      3.43 (95% CI, 1.09, 10.74; RD 0.30 (95% CI, 0.08, 0.53); NNH was 3 (95% CI; 2
      ,13)]. Duration of CSF culture positivity did not differ significantly (MD -1.20
      days (95% CI, -2.67, 0.27). REVIEWERS' CONCLUSIONS: In one trial, enrolling
      infants with gram negative meningitis and ventriculitis, the use of
      intraventricular antibiotics in addition to intravenous antibiotics resulted in a
      3 fold increased RR for mortality compared to standard treatment with intravenous
      antibiotics alone. Based on this result, intraventricular antibiotics as tested
      in this trial should be avoided. Further trials comparing these interventions are
      not justified in this population.

PMID- 15495117
TI  - Long versus short inspiratory times in neonates receiving mechanical ventilation.
AB  - BACKGROUND: When intermittent positive pressure ventilation (IPPV) was introduced
      in newborn infants with hypoxic respiratory failure from hyaline membrane disease
      (HMD), mortality was high and air leaks problematic. This barotrauma was caused
      by the high peak inspiratory pressures (PIP) required to oxygenate stiff lungs.
      The primary determinants of mean airway pressure (and thus oxygenation) on a
      conventional ventilator are the inspiratory time (IT), PIP, positive end
      expiratory pressure and gas flow rates. In the 1970s uncontrolled studies on a
      small number of infants demonstrated a benefit in reducing barotrauma using a
      long IT and slow rates. This strategy was subsequently widely adopted. Current
      neonatal ventilators have been designed to minimise lung injury but rates of
      bronchopulmonary dysplasia (BPD) remain high. It is therefore important that the
      inspiratory time causing least harm is used. OBJECTIVES: To determine in
      mechanically ventilated newborn infants whether the use of a long rather than a
      short IT reduces the rates of death, air leak and BPD. SEARCH STRATEGY: The
      standard search strategy of the Cochrane Neonatal Review Group (CNRG) was used.
      Searches of electronic and other databases were performed. These included MEDLINE
      (1966 - April 2004) and the Cochrane Central Register of Controlled Trials
      (CENTRAL, The Cochrane Library, Issue 4, 2003). In order to detect trials that
      may not have been published, the abstracts of the Society for Pediatric Research,
      and the European Society for Pediatric Research were searched from 1998 - 2003.
      SELECTION CRITERIA: All randomised and quasi-randomised controlled trials
      enrolling mechanically ventilated infants with or without respiratory pathology
      evaluating the use of long versus short IT (including randomised crossover
      studies with outcomes restricted to differences in oxygenation). DATA COLLECTION
      AND ANALYSIS: The standard method of the Cochrane Collaboration and its Neonatal
      Review Group were used. Two authors independently assessed eligibility, and the
      methodological quality of each trial, and extracted the data. The data were
      analysed using relative risk (RR) and risk difference (RD) and their 95%
      confidence intervals. A fixed effect model was used for meta-analyses. MAIN
      RESULTS: In five studies, recruiting a total of 694 infants, a long IT was
      associated with a significant increase in air leak [typical RR 1.56 (1.25, 1.94),
      RD 0.13 (0.07, 0.20), NNT 8 (5, 14)]. There was no significant difference in the
      incidence of BPD. Long IT was associated with an increase in mortality before
      hospital discharge that reached borderline statistical significance [typical RR
      1.26 (1.00, 1.59), RD 0.07 (0.00, 0.13)]. REVIEWERS' CONCLUSIONS: Caution should
      be exercised in applying these results to modern neonatal intensive care, because
      the studies included in this review were conducted prior to the introduction of
      antenatal steroids, post natal surfactant and the use of synchronised modes of
      ventilatory support. Most of the participants had single pathology (HMD) and no
      studies examined the effects of IT on newborns ventilated for other reasons such
      as meconium aspiration and congenital heart disease (lungs with normal
      compliance). However, the increased rates of air leaks and deaths using long ITs
      are clinically important; thus, infants with poorly compliant lungs should be
      ventilated with a short IT.

PMID- 15495118
TI  - Catechol-O-methyltransferase inhibitors versus active comparators for levodopa
      induced complications in Parkinson's disease.
AB  - BACKGROUND: As Parkinson's disease progresses the control of the symptoms often
      requires the addition of other drugs to levodopa. The principle aim of COMT
      inhibitor therapy is to increase the duration of effect of the levodopa dose and
      thus reduce the time patients spend in the relatively immobile 'off' phase.
      OBJECTIVES: To compare the efficacy and safety of adjuvant COMT inhibitor therapy
      versus active comparators in patients with Parkinson's disease, already
      established on levodopa and suffering from motor complications. SEARCH STRATEGY:
      Electronic searches of the Cochrane Controlled Trials Register (The Cochrane
      Library Issue 1, 2003), MEDLINE (1966-2003), EMBASE (1974-2003), were conducted.
      Grey literature was hand searched and the reference lists of identified studies
      and reviews examined. The manufacturers of COMT inhibitors were contacted.
      SELECTION CRITERIA: Randomised controlled trials of adjuvant COMT inhibitor
      therapy versus an active comparator in patients with a clinical diagnosis of
      idiopathic Parkinson's disease and long-term complications of levodopa therapy.
      DATA COLLECTION AND ANALYSIS: Data was abstracted independently by the authors
      and differences settled by discussion. The outcome measures used included
      Parkinson's disease rating scales, levodopa dosage, 'off' time measurements and
      the frequency of withdrawals and adverse events. MAIN RESULTS: Two trials were
      found that examined the efficacy of a COMT inhibitor against an active comparator
      (n = 349). Koller 1998 compared the efficacy of tolcapone versus pergolide (n =
      203) over 12 weeks and TSG 1999 compared the efficacy of tolcapone versus
      bromocriptine (n = 146) over 8 weeks. No trials were found that compared
      entacapone with active comparators. Tolcapone produced similar benefits to
      bromocriptine in 'off' time reduction, motor impairment and disability ratings
      over three months of therapy. Tolcapone produced a greater reduction in levodopa
      dosage than bromocriptine. Tolcapone produced similar benefits to pergolide in
      levodopa dose reduction, motor impairment and disability ratings, and in generic
      health-related quality of life scales over the first two months of therapy.
      Tolcapone produced a greater improvement in the disease-specific quality of life
      scale PDQ-39 than pergolide. Nausea, constipation and orthostatic complaints were
      greater with agonist therapy, but otherwise the frequency of adverse events and
      withdrawals from treatment were similar with the two classes of adjuvant
      medication. One patient had significantly elevated liver enzymes whilst on
      tolcapone, but otherwise the frequency of adverse events and withdrawals from
      treatment were similar. REVIEWERS' CONCLUSIONS: The two trials comparing
      tolcapone with the dopamine agonists bromocriptine and pergolide were
      underpowered to detect clinically relevant differences between them. This is
      based on medium-term evidence. No evidence was found comparing entacapone with
      active comparators. Further larger and longer-term trials are required to compare
      tolcapone with entacapone and COMT inhibitor therapy with alternative adjuvant
      classes of drug in later Parkinson's disease such as dopamine agonists and
      monoamine oxidase inhibitors.

PMID- 15495119
TI  - Catechol-O-methyltransferase inhibitors for levodopa-induced complications in
      Parkinson's disease.
AB  - BACKGROUND: As Parkinson's disease progresses the control of motor symptoms often
      requires the addition of other drugs to levodopa. The principle aim of COMT
      inhibitor therapy is to increase the duration of effect of each levodopa dose and
      thus reduce the time patients spend in the relatively immobile 'off' phase.
      OBJECTIVES: To compare the efficacy and safety of adjuvant COMT inhibitor therapy
      versus placebo in patients with Parkinson's disease, already established on
      levodopa and suffering from motor complications. SEARCH STRATEGY: Electronic
      searches of the Cochrane Controlled Trials Register, (The Cochrane Library Issue
      1, 2003), MEDLINE (1966-2003), EMBASE (1974-2003), were conducted. Grey
      literature was hand searched and the reference lists of identified studies and
      reviews examined. The manufacturers of COMT inhibitors were contacted. SELECTION
      CRITERIA: Randomised controlled trials of adjuvant COMT inhibitor therapy versus
      a placebo in patients with a clinical diagnosis of idiopathic Parkinson's disease
      and long-term complications of levodopa therapy. DATA COLLECTION AND ANALYSIS:
      Data were abstracted independently by the authors and differences settled by
      discussion. The outcome measures used included Parkinson's disease rating scales,
      levodopa dosage, 'off' time measurements and the frequency of withdrawals and
      adverse events. MAIN RESULTS: Fourteen trials fulfilled the inclusion criteria.
      2566 patients with Parkinson's disease and motor fluctuations were included in
      this review. Eight trials examined entacapone versus placebo in a total of 1560
      patients. These trials were between two and twelve months in duration. Six trials
      examined tolcapone versus placebo in a total of 1006 patients. These trials were
      between six weeks and twelve months in duration. Both tolcapone and entacapone
      reduced 'off' time, reduced levodopa dose and modestly improved motor impairments
      and disability. This was at the expense of increased risk of dyskinesias, nausea,
      vomiting, and diarrhoea. A few participants taking tolcapone were found to have
      raised liver enzyme levels. REVIEWERS' CONCLUSIONS: In the management of the
      motor complications seen in Parkinson's disease, tolcapone and entacapone can be
      used to reduce off time, reduce levodopa dose, and modestly improve motor
      impairment and disability. This is based on, at best, medium term evidence.
      However some participants on tolcapone had raised liver enzymes. This combined
      with three cases of fatal hepatic toxicity found during post-marketing
      surveillance has raised concerns over the safety of tolcapone.

PMID- 15495120
TI  - Hyperbaric oxygen therapy for the adjunctive treatment of traumatic brain injury.
AB  - BACKGROUND: Traumatic brain injury is common and presents a health problem with
      significant effect on quality of life. Hyperbaric oxygen therapy (HBOT) has been
      suggested to improve oxygen supply to the injured brain and, therefore, to reduce
      the volume of brain that will ultimately perish. It is postulated that the
      addition of HBOT to the standard intensive care regimen may result in a reduction
      in patient death and disability as a result of these additional brain-preserving
      effects. OBJECTIVES: To assess the benefits and harms of adjunctive HBOT for
      treating traumatic brain injury. SEARCH STRATEGY: We searched CENTRAL (The
      Cochrane Library Issue 4, 2003), MEDLINE (1966 - 2003), EMBASE (1974 - 2003),
      CINAHL (1982 - 2003), DORCTHIM (1996 - 2003), and reference lists of articles.
      Relevant journals were handsearched and researchers in the field were contacted.
      SELECTION CRITERIA: Randomised studies comparing the effect on traumatic brain
      injury of therapeutic regimens which include HBOT with those that exclude HBOT
      (with or without sham therapy). DATA COLLECTION AND ANALYSIS: Three reviewers
      independently evaluated the quality of the relevant trials using the validated
      Oxford-Scale (Jadad 1996) and extracted the data from the included trials. MAIN
      RESULTS: Four trials contributed to this review (382 patients, 199 receiving HBOT
      and 183 control). There was a trend towards, but no significant increase in, the
      chance of a favourable outcome when defined as full recovery, Glasgow outcome
      score 1 or 2, or return to normal activities of daily living (relative risk [RR]
      for good outcome with HBOT 1.94, 95% confidence interval [CI] 0.92 to 4.08,
      P=0.08). Pooled data from the three trials with 327 patients that reported
      mortality, showed a significant reduction in the risk of dying when HBOT was
      added to the treatment regimen (RR 0.69, 95% CI 0.54 to 0.88, P=0.003).
      Heterogeneity between studies was low (I(2) =0%), and sensitivity analysis for
      the allocation of dropouts did not affect that result. This analysis suggests we
      would have to treat seven patients to avoid one extra death (number needed to
      treat [NNT] 7, 95% CI 4 to 22). One trial suggested intracranial pressure was
      favourably lower in those patients receiving HBOT in whom myringotomies had been
      performed (WMD with myringotomy -8.2 mmHg, 95% CI -14.7 mmHg to -1.7 mmHg,
      P=0.01), while in two trials there was a reported incidence of 13% for
      significant pulmonary impairment in the group receiving HBOT versus 0% in the non
      HBOT group (P=0.007). REVIEWERS' CONCLUSIONS: In people with traumatic brain
      injury, the addition of HBOT significantly reduced the risk of death but not of
      favourable clinical outcome. The routine application of HBOT to these patients
      cannot be justified from this review. 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.

PMID- 15495121
TI  - Mannitol and other osmotic diuretics as adjuncts for treating cerebral malaria.
AB  - BACKGROUND: The main treatment for cerebral malaria is parenteral antimalarials.
      Mannitol and urea are used as adjunct therapy for cerebral malaria, but the World
      Health Organization does not recommend them. OBJECTIVES: To compare mannitol or
      urea to placebo or no treatment for treating children and adults with cerebral
      malaria. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group
      Specialized Register (June 2004), CENTRAL (The Cochrane Library Issue 2, 2004),
      MEDLINE (1966 to June 2004), EMBASE (1974 to June 2004), LILACS (1982 to June
      2004), and reference lists of articles. We contacted relevant organizations and
      researchers. SELECTION CRITERIA: Randomized and quasi-randomized controlled
      trials comparing mannitol or urea to placebo or no treatment in children and
      adults with cerebral malaria. DATA COLLECTION AND ANALYSIS: No trials met the
      inclusion criteria. MAIN RESULTS: No trials met the inclusion criteria.
      REVIEWERS' CONCLUSIONS: We identified no randomized or quasi-randomized
      controlled trials to support or refute the use of mannitol or urea as adjuncts
      for treating cerebral malaria in clinical practice. This is likely to require a
      multicentre trial.

PMID- 15495122
TI  - Techniques and materials for closure of the abdominal wall in caesarean section.
AB  - BACKGROUND: There is a variety of techniques for closing the abdominal wall
      during caesarean section. Some methods may be better in terms of postoperative
      recovery and other important outcomes. OBJECTIVES: To compare the effects of
      alternative techniques for closure of the rectus sheath and subcutaneous fat on
      maternal health and healthcare resource use. SEARCH STRATEGY: We searched the
      Cochrane Pregnancy and Childbirth Group trials register (September 2003), MEDLINE
      (1966 to September 2003), EMBASE (1980 to September 2003), CINAHL (1983 to
      September 2003) and CAB Health (1973 to September 2003), and the reference lists
      of included articles. SELECTION CRITERIA: Randomised trials making any of the
      following comparisons: (a) any suturing technique or material used for closure of
      the rectus sheath versus any other; (b) closure versus non-closure of
      subcutaneous fat; (c) any suturing technique or material used for closure of the
      subcutaneous fat versus any other; (d) any type of needle for repair of the
      abdominal wall in caesarean section versus any other; (e) any other comparison of
      methods of abdominal wall closure. DATA COLLECTION AND ANALYSIS: Both reviewers
      evaluated trials for eligibility and methodological quality without consideration
      of their results. MAIN RESULTS: Seven studies involving 2056 women were included.
      The risk of haematoma or seroma was reduced with fat closure compared with non
      closure (relative risk (RR) 0.52, 95% confidence interval (CI) 0.33 to 0.82), as
      was the risk of 'wound complication' (haematoma, seroma, wound infection or wound
      separation) (RR 0.68, 95% CI 0.52 to 0.88). No difference in the risk of wound
      infection alone or other short-term outcomes was found. No long-term outcomes
      were reported. There was no difference in the risk of wound infection between
      blunt needles and sharp needles in one small study. No studies were found
      examining suture techniques or materials for closure of the rectus sheath or
      subcutaneous fat. REVIEWERS' CONCLUSIONS:  IMPLICATIONS FOR PRACTICE: Closure of
      the subcutaneous fat may reduce wound complications but it is unclear to what
      extent these differences affect the well-being and satisfaction of the women
      concerned. IMPLICATIONS FOR RESEARCH: Further trials are justified to investigate
      whether the apparent increased risk of haematoma or seroma with non-closure of
      the subcutaneous fat is real. These should use a broader range of short- and long
      term outcomes, and ensure that they are adequately powered to detect clinically
      important differences. Further research comparing blunt and sharp needles is
      justified, as are trials evaluating suturing materials and suturing techniques
      for the rectus sheath.

PMID- 15495123
TI  - Zhiling decoction for vascular dementia.
AB  - BACKGROUND: Zhiling decoction has a fixed composition of 15 Chinese herbs. The
      properties of each of these herbs and in combination provide the therapeutic
      rationale for a possible action of Zhiling decoction in dilating cerebral vessels
      and increasing cerebral blood flow, as well as reducing serum cholesterol. Thus
      the aim of this review is to evaluate efficacy and safety of Zhiling decoction
      for the treatment of vascular dementia. OBJECTIVES: To assess the efficacy and
      safety of Zhiling decoction for vascular dementia. SEARCH STRATEGY: The
      Specialized Register of the Cochrane Dementia and Cognitive Improvement Group was
      searched on 2 January 2004 using the term Zhiling. This Register contains records
      from all major health care databases and many ongoing trials databases and is
      updated regularly. In addition the reviewers hand searched 83 Chinese Traditional
      Medicine Journals (1993 to 2003). SELECTION CRITERIA: Randomised trials comparing
      Zhiling decoction with placebo in people with vascular dementia. DATA COLLECTION
      AND ANALYSIS: Two reviewers independently assessed trial quality and extracted
      data. Study authors were contacted for additional information. Adverse effects
      information was collected from the trials where possible. MAIN RESULTS: In the
      absence of any suitable randomised placebo-controlled trials in this area, we
      were unable to perform a meta-analysis. REVIEWERS' CONCLUSIONS: The currently
      available evidence is insufficient to assess the potential for Zhiling decoction
      in the treatment of vascular dementia. The little objective data concerning the
      management of Zhiling decoction versus Naofukang suggests that Zhiling decoction
      may be effective in treating vascular dementia. There is no evidence for or
      against Zhiling as a treatment for vascular dementia. Further randomised, double
      blind, placebo-controlled trials are urgently needed in order to define the
      relative efficacy and acceptability of Zhiling in vascular dementia.

PMID- 15495124
TI  - Antimicrobial agents for preventing peritonitis in peritoneal dialysis patients.
AB  - BACKGROUND: Peritoneal dialysis (PD) is used as substitutive treatment of renal
      function in a large proportion (15-50%) of the end-stage kidney disease (ESRD)
      population. The major limitation is peritonitis which leads to technique failure,
      hospitalisation and increased mortality. Oral, nasal, topical antibiotic
      prophylaxis, exit-site disinfectants and other antimicrobial interventions are
      used to prevent peritonitis. OBJECTIVES: The objective of this systematic review
      of randomised controlled trials (RCTs) was to evaluate what evidence supports the
      use of different antimicrobial approaches to prevent peritonitis in PD. SEARCH
      STRATEGY: The Cochrane CENTRAL Registry (issue 1, 2004), MEDLINE (1966-May 2003),
      EMBASE (1988-May 2003) and reference lists were searched for RCTs of
      antimicrobial agents in PD. SELECTION CRITERIA: Trials of the following agents
      were included: antibiotics by any route (oral, nasal, topical), exit-site
      disinfectants (chlorhexidine, povidone iodine, soap and water), vaccines, and
      ultraviolet germicidal devices. DATA COLLECTION AND ANALYSIS: Two reviewers
      extracted data on the number of patients with one or more episodes and rates of
      peritonitis and exit-site/tunnel infection, catheter removal, catheter
      replacement, technique failure, toxicity of antibiotic treatments, all-cause
      mortality. Statistical analyses were performed using the random effects model and
      the results expressed as relative risk (RR) with 95% confidence intervals (CI).
      MAIN RESULTS: Nineteen trials, enrolling 1949 patients met our inclusion
      criteria. Nasal mupirocin compared with placebo significantly reduced the exit
      site and tunnel infection rate (one trial, 2716 patient months, RR 0.58, 95% CI
      0.40 to 0.85) but not peritonitis rate (one trial, 2716 patient months, RR 0.84,
      95% CI 0.44 to 1.60). Perioperative intravenous antibiotics compared with no
      treatment significantly reduced the risk of early peritonitis (four trials, 335
      patients, RR 0.35, 95% CI 0.15 to 0.80) but not exit site and tunnel infection
      (three trials, 114 patients, RR 0.32, 95% CI 0.02 to 4.81). No intervention
      reduced the risk of catheter removal or replacement. REVIEWERS' CONCLUSIONS: This
      review demonstrates that nasal mupirocin reduces exit-site/tunnel infection but
      not peritonitis. Preoperative intravenous prophylaxis reduces early peritonitis
      but not exit-site/tunnel infection. No other antimicrobial interventions have
      proven efficacy. Given the large number of patients on PD and the importance of
      peritonitis, the lack of adequately powered RCTs to inform decision making about
      strategies to prevent peritonitis is striking.

PMID- 15495125
TI  - Catheter type, placement and insertion techniques for preventing peritonitis in
      peritoneal dialysis patients.
AB  - BACKGROUND: As many as 15-50% of end-stage kidney disease patients are on
      peritoneal dialysis (PD), but peritonitis limits its more widespread use. Several
      PD catheter-related interventions have been purported to reduce the risk of
      peritonitis in PD. OBJECTIVES: To evaluate the use of catheter-related
      interventions for the prevention of peritonitis in PD. SEARCH STRATEGY: The
      Cochrane Renal Group's specialised register (June 2004), The Cochrane CENTRAL
      Register of Controlled Trials (The Cochrane Library Issue 2 2004), MEDLINE (1966
      April 2004), EMBASE (1988-April 2004) and reference lists were searched without
      language restriction SELECTION CRITERIA: Trials comparing different catheter
      insertion techniques, catheter types, use of immobilisation techniques or
      different break in periods were included. Trials of different PD sets were
      excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed
      trial quality and extracted data. Statistical analyses were performed using a
      random effects model and the results expressed as relative risk (RR) with 95%
      confidence intervals (CI). MAIN RESULTS: Seventeen eligible trials (1089
      patients) were identified, eight of surgical strategies of catheter insertion,
      eight of straight versus coiled catheters, one of single cuff versus double cuff
      catheters and one of an immobiliser device. The methodological quality was
      suboptimal. There were no significant differences with laparoscopy compared with
      laparotomy for peritonitis, the peritonitis rate, exit-site/tunnel infection or
      catheter removal/replacement. Standard insertion with resting but no subcutaneous
      burying of the catheter versus implantation and subcutaneous burying was not
      associated with a significant reduction in peritonitis rate, exit-site/tunnel
      infection rate or all-cause mortality. Midline compared to lateral insertion
      showed no significant difference in the risk of peritonitis or exit-site/tunnel
      infection. There was no significant difference in the risk of peritonitis,
      peritonitis rate, exit-site/tunnel infection, exit-site/tunnel infection rate or
      catheter removal/replacement between straight versus coiled intraperitoneal
      portion catheters. One trial compared single versus double cuffed catheters and
      showed no significant difference in the risk of peritonitis, exit-site/tunnel
      infection or catheter removal/replacement. One trial compared immobilisation
      versus no immobilisation of the PD catheter and showed no significant difference
      in the risk of peritonitis and exit-site/tunnel infection. No trials of different
      break-in periods were identified. REVIEWERS' CONCLUSIONS: No major advantages
      from any of the catheter-related interventions which have been purported to
      reduce the risk of PD peritonitis could be demonstrated in this review. The
      frequency and quality of available trials are suboptimal.

PMID- 15495126
TI  - Transdermal nicotine for induction of remission in ulcerative colitis.
AB  - BACKGROUND: Ulcerative colitis is largely a disease of nonsmokers. Intermittent
      smokers often experience improvement in their symptoms while smoking. Nonsmokers
      with ulcerative colitis who begin smoking may go into remission. Randomized
      controlled trials were developed to test the efficacy of transdermal nicotine for
      the induction of remission in ulcerative colitis. OBJECTIVES: (1) To determine
      the efficacy of transdermal nicotine for induction of remission in ulcerative
      colitis. (2) To assess adverse events associated with transdermal nicotine
      therapy for ulcerative colitis SEARCH STRATEGY: The MEDLINE (via PubMed) and
      EMBASE databases were searched using the search criteria "ulcerative colitis" and
      "transdermal nicotine" or "nicotine" to identify relevant papers published
      between 1970 and December 2003. Manual searches of reference lists from
      potentially relevant papers were performed to identify additional studies.
      Abstracts from major gastroenterological meetings were searched to identify
      research submitted in abstract form only. The Cochrane Central Register of
      Controlled Trials and the Cochrane Inflammatory Bowel Disease Group Specialized
      Trials Register were also searched. SELECTION CRITERIA: We included only
      randomized controlled trials in which patients with active mild to moderate
      ulcerative colitis were randomly allocated to receive transdermal nicotine (15 to
      25 mg/day) or a placebo or another treatment (corticosteroids or mesalamine).
      DATA COLLECTION AND ANALYSIS: Data extraction and assessment of the
      methodological quality of each trial were independently performed by each author.
      Any disagreement among reviewers was resolved by consensus. The primary outcome
      measure was the number of patients achieving clinical or sigmoidoscopic remission
      as defined by the primary studies (e.g. no symptoms of ulcerative colitis), and
      expressed as a percentage of the patients randomized (intention to treat
      analysis). Secondary outcomes included clinical response, adverse events and
      withdrawal because of adverse events. MAIN RESULTS: Seven studies were
      identified, five of which met the inclusion criteria. A meta-analysis of two
      trials in which 71 patients were randomized to nicotine and 70 to placebo showed
      a statistically significant benefit for nicotine treatment. After four to six
      weeks of treatment 19 of 71 patients treated with transdermal nicotine were in
      clinical remission compared to 9 of 70 treated with placebo (OR=2.56, 95% CI 1.02
      6.45). In the same group of patients improvement or remission was noted in 29 of
      the 71 patients assigned to nicotine compared to 14 of 70 patients assigned to
      placebo (OR=2.72, 95% CI 1.28 - 5.81). For patients with left sided colitis the
      odds ratio was 2.31 (95% CI 1.05-5.10). When transdermal nicotine was compared to
      standard medical therapy no significant benefit for nicotine was observed. After
      four to six weeks of standard therapy (oral prednisone or mesalamine), 34 of 63
      patients were in clinical or sigmoidoscopic remission compared to 33 of 66
      patients treated with transdermal nicotine (OR=0.77, 95% CI 0.37-1.60). A meta
      analysis of all five studies which included 137 patients treated with transdermal
      nicotine and 133 patients treated with a placebo or standard therapy demonstrated
      no statistically significant benefit of nicotine therapy (OR=1.23; 95% CI 0.71
      2.14). Patients treated with transdermal nicotine were significantly more likely
      to withdrawal due to adverse events than patients treated with placebo or
      standard medical therapy (OR=5.82, 95% CI, 1.66 - 20.47) and were significantly
      more likely to suffer from an adverse event than patients treated with placebo or
      standard medical therapy (OR=3.54, 95% CI, 2.07 - 6.08). REVIEWERS' CONCLUSIONS:
      The results of this review provide evidence that transdermal nicotine is superior
      to placebo for the induction of remission in patient's with ulcerative colitis.
      The review did not identify any significant advantage for transdermal nicotine
      therapy compared to standard medical therapy. Adverse events associated with
      transdermal nicotine are significant and limit its use in some patients.

PMID- 15495127
TI  - D-penicillamine for primary biliary cirrhosis.
AB  - BACKGROUND: D-penicillamine is used for patients with primary biliary cirrhosis
      due to its hepatic copper decreasing and immunomodulatory potentials. The results
      from randomised clinical trials have been inconsistent. OBJECTIVES: To
      systematically review the beneficial and harmful effects of D-penicillamine for
      patients with primary biliary cirrhosis. SEARCH STRATEGY: We identified trials
      through electronic searches of The Cochrane Hepato-Biliary Group Controlled
      Trials Register (September 2003), The Cochrane Central Register of Controlled
      Trials on The Cochrane Library (Issue 3, 2003), MEDLINE (January 1966 to
      September 2003), EMBASE (January 1980 to September 2003), The Chinese Biomedical
      CD Database (January 1979 to August 2003), and LILACS (1982 to 2003); through
      manual searches of bibliographies; and by contacting authors of the trials and
      pharmaceutical companies. SELECTION CRITERIA: We included randomised clinical
      trials comparing D-penicillamine with placebo/no intervention or other control
      intervention irrespective of language, year of publication, and publication
      status. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the
      methodological quality of the trials and extracted data, validated by a third
      reviewer. The primary outcomes were 1) mortality and 2) a combination of those
      who died or underwent liver transplantation. We analysed dichotomous outcomes as
      relative risk (RR) with 95% confidence interval (CI) by a fixed effect model and
      a random effects model. We investigated sources of heterogeneity by subgroup
      analyses and tested the robustness of our findings by sensitivity analyses. MAIN
      RESULTS: We included seven trials randomising 706 patients with primary biliary
      cirrhosis. D-penicillamine compared with placebo/no intervention tended to
      increase mortality (RR 1.34, 95% CI 1.09 to 1.64, fixed; RR 1.46, 95% CI 0.85 to
      2.50, random). However, there was substantial heterogeneity. No significant
      differences were detected regarding the risks of mortality or liver
      transplantation, pruritus, liver complications, progression of liver histological
      stage, or the levels of liver biochemical variables (except alanine
      aminotransferase). D-penicillamine versus placebo/no intervention significantly
      increased the risk of adverse events (RR 3.11, 95% CI 2.33 to 4.16, fixed; RR
      4.18, 95% CI 1.38 to 12.69, random). REVIEWERS' CONCLUSIONS: D-penicillamine did
      not appear to reduce the risk of mortality, but significantly increased the
      occurrences of adverse events in patients with primary biliary cirrhosis. We do
      not support the use of D-penicillamine for patients with primary biliary
      cirrhosis.

PMID- 15495128
TI  - Fertility awareness-based methods for contraception.
AB  - BACKGROUND: "Fertility awareness-based methods" (FAB) of family planning "involve
      identification of the fertile days of the menstrual cycle, whether by observing
      fertility signs such as cervical secretions and basal body temperature, or by
      monitoring cycle days. FAB methods can be used in combination with abstinence or
      barrier methods during the fertile time" (WHO 2000). Several names have been used
      to describe this approach to contraception, including "rhythm," "natural family
      planning" and "periodic abstinence." Fertility awareness-based methods can be
      used with abstinence from sexual intercourse. Alternatively, they can be used
      with barrier contraceptives or withdrawal during presumed fertile times.
      OBJECTIVES: We retrieved and analyzed all randomized controlled trials that
      examined any fertility awareness-based methods used for contraception. SEARCH
      STRATEGY: We searched the computerized databases Cochrane Central Register of
      Controlled Trials (CENTRAL), MEDLINE, POPLINE, EMBASE, and LILACS (each from its
      inception to January, 2004) for randomized controlled trials of fertility
      awareness-based methods. We examined the reference list of each trial as well as
      that of review articles. SELECTION CRITERIA: We included all randomized
      controlled trials in any language that compared any fertility awareness-based
      methods for contraception with a placebo; another method, including an
      alternative fertility awareness-based method; or fertility awareness-based
      methods used in conjunction with another contraceptive. DATA COLLECTION AND
      ANALYSIS: We assessed all titles and abstracts found for inclusion. We evaluated
      the methodological quality of the trials for potential biases by qualitatively
      assessing the study design; randomization method; allocation concealment;
      blinding; premature discontinuation rates; and loss to follow-up rates. Because
      of methodological weaknesses, we could not enter the trial results in RevMan,
      calculate measures of association, or aggregate data. MAIN RESULTS: Because of
      poor methods and reporting, pregnancy rates could not be determined. A trial in
      Colombia found similar numbers of pregnancies among women randomized to the
      ovulation and symptothermal methods. In contrast, a companion trial in Los
      Angeles observed more pregnancies in the group assigned to the ovulation method.
      In the two U.S. trials, recruitment of participants was unexpectedly difficult;
      this aspect was not mentioned in the report from Colombia. Continuation rates
      were poor. In the two larger trials, most participants discontinued their
      assigned method before entering the observation phase of the trial. REVIEWERS'
      CONCLUSIONS: The comparative efficacy of fertility awareness-based methods of
      contraception remains unknown. Despite intensive training and ongoing support,
      most participants in these trials discontinued prematurely. Contraceptive methods
      should be properly evaluated, preferably in randomized controlled trials, before
      adoption and dissemination.

PMID- 15495129
TI  - Antifibrinolytic drugs for acute traumatic injury.
AB  - BACKGROUND: Uncontrolled bleeding is an important cause of death in trauma
      victims. Antifibrinolytic treatment has been shown to reduce blood loss following
      surgery and may also be effective in reducing blood loss following trauma.
      OBJECTIVES: To quantify the effect of antifibrinolytic drugs in reducing blood
      loss, transfusion requirement and mortality after acute traumatic injury. SEARCH
      STRATEGY: We searched the Cochrane Injuries Group's Specialised Register, the
      Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, EMBASE, Science
      Citation Index, National Research Register, Zetoc, SIGLE, Global Health, LILACS,
      and Current Controlled Trials. SELECTION CRITERIA: We included all randomised
      controlled trials of antifibrinolytic agents (aprotinin, tranexamic acid [TXA]
      and epsilon-aminocaproic acid) following acute traumatic injury. DATA COLLECTION
      AND ANALYSIS: The titles and abstracts identified in the electronic searches were
      screened by two independent reviewers to identify studies that had the potential
      to meet the inclusion criteria. The full reports of all such studies were
      obtained. From the results of the screened electronic searches, bibliographic
      searches, and contacts with experts, two reviewers independently selected trials
      meeting the inclusion criteria, with any disagreements resolved by consensus.
      MAIN RESULTS: Two studies met the inclusion criteria. The study by Auer (1979),
      with 20 randomised patients, provided no useable outcome data. The study by
      McMichan (1982), with 77 randomised patients, was reported in four separate
      reports. Outcome data were reported for death, the proportion undergoing surgical
      intervention and the volume of blood transfused. Because of the small number of
      randomised participants, the estimates for each of these outcomes were highly
      imprecise. Data on the proportion undergoing re-operation and the proportion
      receiving blood transfusion were not reported. REVIEWERS' CONCLUSIONS: There is
      insufficient evidence from randomised controlled trials of antifibrinolytic
      agents in trauma to either support or refute a clinically important treatment
      effect. Further randomised controlled trials of antifibrinolytic agents in trauma
      are required.

PMID- 15495130
TI  - Single or double-level anterior interbody fusion techniques for cervical
      degenerative disc disease.
AB  - BACKGROUND: The number of surgical techniques for decompression and solid
      interbody fusion as a treatment for cervical spondylosis has increased rapidly,
      but the rationale for the choice between different techniques is unclear.
      OBJECTIVES: The goal of this study was to determine which method of anterior
      cervical interbody fusion at a single or double-level provides the best clinical
      and radiological outcome in patients with degenerative disc disease. SEARCH
      STRATEGY: Studies were identified with a computer-assisted search of electronic
      databases in the Cochrane Central Register of Controlled Trials (Issue 1, 2004),
      MEDLINE (1966 to 2004), EMBASE (1980 to 2004), and Current Contents (1996 to
      2004). We also searched references of selected articles. SELECTION CRITERIA: With
      the aid of a checklist, two reviewers independently screened the identified
      references. Consensus was reached through negotiation. A third reviewer was
      consulted if consensus could not be reached. Inclusion criteria included:
      articles were reports of randomised comparative studies; treatments compared
      anterior cervical decompression and interbody fusion techniques, participants
      were individuals scheduled for surgery for a chronic (longer than 12 weeks)
      diagnosis of degenerative disc disease. DATA COLLECTION AND ANALYSIS:
      Methodological quality was assessed independently by two reviewers, using the van
      Tulder list of criteria. With the aid of a data extraction form, data was
      extracted independently by two reviewers on group characteristics, intervention
      details and outcome measures. MAIN RESULTS: Fourteen studies with 939 patients
      evaluated three comparisons of different fusion techniques. From these
      comparisons it appears that discectomy alone has a shorter operation time,
      hospital stay, and post-operative absence from work than discectomy with fusion,
      while there is no statistical difference for pain relief and rate of fusion. It
      also appears that fusion techniques that use autograft give a better chance for
      fusion than interbody fusion techniques that use a cage, but other outcome
      variables could not be combined. REVIEWERS' CONCLUSIONS: The low quality of the
      trials prohibits extensive conclusions from this review. More studies with better
      methodology and reporting are needed. There should be a more general agreement
      between researchers on which outcome parameters should be used in the evaluation
      of anterior cervical fusion procedures.

PMID- 15495131
TI  - Amphetamines for schizophrenia.
AB  - BACKGROUND: It is estimated that between 10% and 65% of people with schizophrenia
      use illicit drugs such as amphetamines. This group have an increased rate of
      hospitalisation, homelessness, unemployment and suicide compared with those with
      schizophrenia who do not abuse drugs. OBJECTIVES: To evaluate the effects of
      amphetamines for people with schizophrenia in terms of clinically meaningful
      outcomes, cognitive functioning and physiological tests. SEARCH STRATEGY: We
      searched the Cochrane Schizophrenia Group's Register (February 2002). SELECTION
      CRITERIA: We included all randomised controlled trials investigating the effects
      of amphetamines on people with schizophrenia, compared with a placebo
      intervention. 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 we calculated Weighted Mean Differences (WMD). MAIN RESULTS: We
      included four short studies with a total of 83 participants. Data were few and
      poorly reported. The results indicated a reduction of negative symptoms for
      people allocated to amphetamines (n = 16, 1 RCT, WMD -3 CI -5.02 to -0.98). No
      such effect was found for positive symptom change (n = 16, 1 RCT, WMD 0 CI -4.46
      to 4.46). Compared with placebo, amphetamines significantly increased metabolism
      in the left and right cerebellum (n = 23, 1 RCT, WMD 0.12 CI 0.06 to 0.18; n = 23
      1 RCT, WMD 0.12 CI 0.06 to 0.18) and left striatum (n = 23, 1 RCT, WMD 0.14 CI
      0.00 to 0.28) and also significantly decreased metabolism in the left
      dorsolateral prefrontal cortex (n = 23, 1 RCT, WMD -0.09 CI -0.17 to -0.01).
      REVIEWERS' CONCLUSIONS: Understandably amphetamines are rarely formally evaluated
      in randomised studies and therefore unpublished work in this area is likely to
      exist. Addition of more studies may clarify reasons why people with schizophrenia
      persist in taking these harmful stimulants.

PMID- 15495132
TI  - Interventions for replacing missing teeth: treatment of perimplantitis.
AB  - BACKGROUND: One of the key factors for the long-term success of oral implants is
      the maintenance of healthy tissues around them. Bacterial plaque accumulation
      induces inflammatory changes in the soft tissues surrounding oral implants and it
      may lead to their progressive destruction (perimplantitis) and ultimately to
      implant failure. Different treatment strategies for perimplantitis have been
      suggested, however it is unclear which are the most effective. OBJECTIVES: To
      identify the most effective interventions for treating perimplantitis around
      osseointegrated dental implants. SEARCH STRATEGY: We searched the Cochrane Oral
      Health Group's Trials Register, the Cochrane Central Register of Controlled
      Trials (CENTRAL), MEDLINE and EMBASE. Handsearching included several dental
      journals. We checked the bibliographies of the identified randomised controlled
      trials (RCTs) and relevant review articles for studies outside the handsearched
      journals. We wrote to authors of all identified RCTs, to more than 55 oral
      implant manufacturers and an internet discussion group to find unpublished or
      ongoing RCTs. No language restrictions were applied. The last electronic search
      was conducted on 28 June 2004. SELECTION CRITERIA: All RCTs of oral implants
      comparing agents or interventions for treating perimplantitis around dental
      implants. DATA COLLECTION AND ANALYSIS: Screening of eligible studies, assessment
      of the methodological quality of the trials and data extraction were conducted in
      duplicate and independently by two reviewers. We contacted the authors for
      missing information. Results were expressed as random effect models using
      weighted mean differences for continuous outcomes and relative risk for
      dichotomous outcomes with 95% confidence interval (CI). Heterogeneity was to be
      investigated including both clinical and methodological factors. MAIN RESULTS:
      Only two eligible trials were identified, but one was excluded due to
      insufficient data presented. The included study compared the use of locally
      applied metronidazole gel versus ultrasonic debridement in patients affected
      possibly by a slight form of perimplantitis. Both interventions were repeated 1
      week after. Twelve weeks after treatment there was no statistically significant
      difference in probing pocket depths among the two groups (mean difference = 0.1;
      95% CI -0.59 to 0.79). No side effects occurred. This trial was judged to be at
      high risk of bias. REVIEWERS' CONCLUSIONS: There is no reliable evidence
      suggesting which could be the most effective interventions for treating
      perimplantitis. This is not to say that currently used interventions are not
      effective. More quality research is needed.

PMID- 15495133
TI  - Pneumococcal conjugate vaccines for preventing vaccine-type invasive pneumococcal
      disease and pneumonia with consolidation on x-ray in children under two years of
      age.
AB  - BACKGROUND: Pneumonia, most commonly caused by Streptococcus pneumoniae (Pnc), is
      a major cause of morbidity and mortality among young children especially in
      developing countries. Recently, the prevalence of antibiotic-resistant Pnc has
      increased worldwide such that the effectiveness of preventive strategies, like
      the new pneumococcal conjugate vaccines (PCV) on rates of invasive pneumococcal
      disease (IPD) and pneumonia, needs to be evaluated. OBJECTIVES: To determine the
      efficacy of PCV in reducing the incidence of IPD due to vaccine serotypes (VT)
      and x-ray confirmed pneumonia with consolidation of unspecified etiology in
      children who received PCV before 12 months of age. SEARCH STRATEGY: We searched
      the following databases: the Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library, Issue 1 2004), MEDLINE (1990 to March 2004) and
      EMBASE (1990 to December 2003). Reference list of articles, and books of
      abstracts of relevant symposia, were hand searched. Researchers in the field were
      also contacted. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing
      PCV with placebo, or another vaccine, among children below two years with IPD and
      clinical/radiographic pneumonia as outcomes. DATA COLLECTION AND ANALYSIS: Two
      reviewers independently identified eligible studies, assessed trial quality, and
      extracted data. Differences were resolved by discussion. The inverse variance
      method was used to pool effect sizes. MAIN RESULTS: We identified four trials
      assessing the efficacy of PCV in reducing the incidence of IPD, two on x-ray
      confirmed pneumonia as outcome, and one on clinical pneumonia, with or without x
      ray confirmation. Results from pooling HIV-1 negative children from the South
      African study with the other studies were as follows: the pooled vaccine efficacy
      (VE) for vaccine-type IPD was 88% (95% confidence interval (CI) 73% to 94%; fixed
      effect and random effects models), the effect measure was statistically
      significant (p <0.00001) and there was no heterogeneity (p = 0.77I2 0%); the
      pooled VE for all-serotype IPD was 66% (95% CI 46% to 79%; fixed effect model),
      the effect measure was statistically significant (p <0.00001) and there was no
      statistical heterogeneity (p = 0.09, I2 51%); the pooled VE for x-ray confirmed
      pneumonia was 22% (95% CI 11% to 31%; both fixed effect and random effects
      models) and there was no statistical heterogeneity (p = 0.80, I2 0%). Analyses
      that included all the children in the South African study (HIV-1 negative and HIV
      1 positive children) and pooled with data from the other studies gave very
      similar results. REVIEWERS' CONCLUSIONS: PCV is effective in reducing the
      incidence of IPD from all serotypes but exerts a greater effect in reducing VT
      IPD. Although PCV is also effective in reducing the incidence of x-ray confirmed
      pneumonia, there are still uncertainties about the definition of this outcome.
      Additional randomised controlled trials are currently in progress.

PMID- 15495134
TI  - Surgery versus sclerotherapy for the treatment of varicose veins.
AB  - BACKGROUND: Varicose veins are a relatively common condition and account for
      around 54,000 in-patient hospital episodes per year. The two most common
      interventions for varicose veins are surgery and sclerotherapy. However, there is
      little comparative data regarding their effectiveness. OBJECTIVES: To identify
      whether the use of surgery or sclerotherapy should be recommended for the
      management of primary varicose veins. SEARCH STRATEGY: Thirteen electronic
      bibliographic databases were searched covering biomedical, science, social
      science, health economic and grey literature (including current research). In
      addition, the reference lists of relevant articles were checked and various
      health services research-related resources were consulted via the internet. These
      included health economics and HTA organisations, guideline producing agencies,
      generic research and trials registers, and specialist sites. SELECTION CRITERIA:
      All studies that were described as randomised controlled trials comparing surgery
      with sclerotherapy for the treatment of primary varicose veins were identified.
      DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted and
      summarised data from the eligible studies using a data extraction sheet for
      consistency. All studies were cross-checked independently by the reviewers. MAIN
      RESULTS: A total of 2306 references were found from our searches, 61 of which
      were identified as potential trials comparing surgery and sclerotherapy. However,
      only nine randomised trials, described in a total of 14 separate papers,
      fulfilled the inclusion criteria. Fifty trials were excluded and one trial is
      ongoing and is due for completion in 2004. The trials used a variety of outcome
      measures and classification systems which made direct comparison between trials
      difficult. However, the trend was for sclerotherapy to be evaluated as
      significantly better than surgery at one year; after one year (sclerotherapy
      resulted in worse outcomes) the benefits with sclerotherapy were less, and by
      three to five years surgery had better outcomes. The data on cost-effectiveness
      was not adequately reported. REVIEWERS' CONCLUSIONS: There was insufficient
      evidence to preferentially recommend the use of sclerotherapy or surgery. There
      needs to be more research that specifically examines both costs and outcomes for
      surgery and sclerotherapy.

PMID- 15495135
TI  - Trazodone for agitation in dementia.
AB  - BACKGROUND: Behavioural and psychiatric disturbances affect at least 50% of
      people with Alzheimer's disease and other dementias. Neuroleptic drugs are
      extensively prescribed to treat behavioural manifestations of dementia in spite
      of only modest efficacy and a high frequency of adverse effects. There is clearly
      a need for safer and more effective remedies. Trazodone is a psychoactive
      compound with sedative and antidepressant properties, and with mixed serotonin
      agonist and antagonist effects. Functional serotonergic deficits may be related
      to the genesis of behavioural disturbances in dementia. OBJECTIVES: To determine
      the clinical efficacy and safety of trazodone, for any type of behavioural or
      psychological cognition in people with dementia without an additional diagnosis
      of depression. SEARCH STRATEGY: Trials were identified from a search of the
      Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on
      1 June 2004 using the terms trazodon*, beneficat, desirel, sideril, trazodil,
      trazalon. This register contains records from all major health care databases and
      many ongoing trials databases, and is updated regularly. SELECTION CRITERIA: All
      unconfounded, double-blind, randomised controlled trials, comparing trazodone
      with placebo in managing behavioural and psychiatric symptoms (except depression)
      in any type of dementia. DATA COLLECTION AND ANALYSIS: Available data for this
      analysis were extracted from the two included studies and odds ratios or average
      differences, with 95% confidence intervals, calculated. Intention-to-treat
      analysis was undertaken where possible. MAIN RESULTS: Two studies were included,
      comprising 104 participants with dementia. The trials differed in design - one
      being a parallel-group study of patients with Alzheimer's disease (Teri 2000) and
      one being a cross-over study of patients with frontotemporal dementia (Lebert
      2004). It was not possible to pool the data. The studies were respectively of 16
      and 6 weeks duration, using trazodone from 50 to 300mg daily. Both trials
      examined global clinical state, behavioural disturbances and cognitive function.
      Teri 2000 also assessed activities of daily living and caregiver burden. Compared
      with placebo, the use of trazodone was not associated with statistically
      significant benefits for behavioural manifestations as measured by various rating
      scales (ABID, CERAD-BRSD,CMAI, NPI). Analysis of changes from baseline for
      clinical impression of change and for cognitive function did not produce
      statistically significant results in favour of trazodone. A variety of adverse
      effects were recorded with no significant differences between trazodone and
      placebo. REVIEWERS' CONCLUSIONS: There is insufficient evidence to recommend the
      use of trazodone as a treatment for behavioural and psychological manifestations
      of dementia. In order to assess effectiveness and safety of trazodone, longer
      term trials are needed, involving larger samples of participants with a wider
      variety of types and severities of dementia.

PMID- 15495136
TI  - Psychosocial and pharmacological treatments versus pharmacological treatments for
      opioid detoxification.
AB  - BACKGROUND: Different pharmacological approaches aimed at opioid detoxification
      are effective. Nevertheless a majority of patients relapse to heroin use, and
      relapses are a substantial problem in the rehabilitation of dependent heroin
      users. Some studies have suggested that the sorts of symptoms which are most
      distressing to addicts during detoxification are psychological symptoms rather
      than physiological symptoms associated with the withdrawal syndrome. OBJECTIVES:
      To evaluate the effectiveness of any psychosocial plus any pharmacological
      interventions versus any pharmacological alone for opioid detoxification, in
      helping patients to complete the treatment, reduce the use of substances and
      improve health and social status. SEARCH STRATEGY: We searched the Cochrane
      Central Register of Trials (CENTRAL) issue 3, 2003; MEDLINE 1966-2003; EMBASE
      1980-2003; PsycINFO 1985-2003; relevant web sites; scan of reference list of
      relevant articles. There were no language or publication restrictions. SELECTION
      CRITERIA: Randomised controlled trials which focus on any psychosocial associated
      with any pharmacological intervention aimed at opioid detoxification. People less
      than 18 years of age and pregnant women were excluded. DATA COLLECTION AND
      ANALYSIS: The trials were independently assessed for inclusion and methodological
      quality by three reviewers. Data were extracted independently and double checked.
      MAIN RESULTS: The searching process resulted in the identification of 77
      different studies: 8 studies met inclusion criteria. These studies considered 5
      different psychosocial interventions and 2 substitution detoxification
      treatments: Methadone and Buprenorphine. The results show promising benefit from
      adding any psychosocial treatment to any substitution detoxification treatment in
      terms of completion of treatment RR 1.68 (95% CI 1.11-2.55), results at follow-up
      RR 2.43 (95% CI 1.61-3.66), and compliance RR 0.48 (95% CI 0.38-0.59). In respect
      of the use of heroin during the treatment, the differences were not statistically
      significant but favoured the combined treatments. REVIEWERS' CONCLUSIONS:
      Psychosocial treatments offered in addition to pharmacological detoxification
      treatments are effective in terms of completion of treatment, results at follow
      up and compliance. Although a treatment, like detoxification, that exclusively
      attenuates the severity of opiate withdrawal symptoms can be at best partially
      effective for a chronic relapsing disorder like opiate dependence, this type of
      treatment is an essential step prior to longer-term drug-free treatment and it is
      desirable to develop adjunct psychosocial approaches that might make
      detoxification more effective. Limitations to this review are imposed by the
      heterogeneity of the assessment of outcomes. Because of lack of detailed
      information no meta analysis could be performed to analyse the results related to
      several outcomes.

PMID- 15495137
TI  - Relationship between multiple sequence alignments and quality of protein
      comparative models.
AB  - Comparative modeling is the method of choice, whenever applicable, for protein
      structure prediction, not only because of its higher accuracy compared to
      alternative methods, but also because it is possible to estimate a priori the
      quality of the models that it can produce, thereby allowing the usefulness of a
      model for a given application to be assessed beforehand. By and large, the
      quality of a comparative model depends on two factors: the extent of structural
      divergence between the target and the template and the quality of the sequence
      alignment between the two protein sequences. The latter is usually derived from a
      multiple sequence alignment (MSA) of as many proteins of the family as possible,
      and its accuracy depends on the number and similarity distribution of the
      sequences of the protein family. Here we describe a method to evaluate the
      expected difficulty, and by extension accuracy, of a comparative model on the
      basis of the MSA used to build it. The parameter that we derive is used to
      compare the results obtained in the last two editions of the Critical Assessment
      of Methods for Structure Prediction (CASP) experiment as a function of the
      difficulty of the modeling exercise. Our analysis demonstrates that the
      improvement in the scope and quality of comparative models between the two
      experiments is largely due to the increased number of available protein sequences
      and to the consequent increased chance that a large and appropriately spaced set
      of protein sequences homologous to the proteins of interest is available.

PMID- 15495138
TI  - Trends in the incidence of acquired immunodeficiency syndrome-related
      malignancies in Thailand.
AB  - BACKGROUND: Thailand was one of the first Asian countries to be affected by the
      epidemic of human immunodeficiency virus/acquired immunodeficiency syndrome
      (HIV/AIDS). Furthermore, Thailand possesses a national cancer surveillance system
      based upon regional cancer registries. METHODS: Data from five population-based
      cancer registries, covering one-fifth of the national population, were used to
      study trends in the incidence of malignancies related to HIV/AIDS in Thailand
      during the period 1989-2001. RESULTS: Although the incidence of Kaposi sarcoma
      (KS) increased slightly from 1989-1991 to 1995-1997, KS remains a very rare
      malignancy in Thailand compared with other countries in which the prevalence of
      HIV/AIDS is much lower. The authors reported a marked increase in the incidence
      of non-Hodgkin lymphoma (NHL), and particularly high-grade/diffuse NHL. However,
      the largest increases in incidence were noted among individuals age >/= 55 years
      and in regions with a relatively low prevalence of HIV/AIDS. CONCLUSIONS: The
      rarity of KS presumably reflected the low prevalence of the causative agent
      (i.e., KS-associated herpesvirus) in the Thai population. The increasing
      incidence of NHL may be related to the AIDS epidemic, although a similar increase
      is observed in many countries worldwide and is not specifically linked to the
      HIV/AIDS epidemic.

PMID- 15495139
TI  - State of the Art Symposium-prescreening and rescreening of cervical vaginal
      cytology specimens.

PMID- 15495140
TI  - Mass spectrometry in aging research.
AB  - This review covers the application of mass spectrometric techniques to aging
      research. Modern proteomic strategies will be discussed as well as the targeted
      analysis of specific proteins for the correlation of post-translational
      modifications with protein function. Selected examples will show both the power
      and also current limitations of the respective techniques. Experimental results
      and strategies are discussed in view of current theories of the aging process.

PMID- 15495141
TI  - Comparative proteomics analysis of human pituitary adenomas: current status and
      future perspectives.
AB  - This article will review the published research on the elucidation of the
      mechanisms of pituitary adenoma formation. Mass spectrometry (MS) plays a key
      role in those studies. Comparative proteomics has been used with the long-term
      goal to locate, detect, and characterize the differentially expressed proteins
      (DEPs) in human pituitary adenomas; to identify tumor-related and -specific
      biomarkers; and to clarify the basic molecular mechanisms of pituitary adenoma
      formation. The methodology used for comparative proteomics, the current status of
      human pituitary proteomics studies, and future perspectives are reviewed. The
      methodologies that are used in comparative proteomics studies of human pituitary
      adenomas are readily exportable to other different areas of cancer research.

PMID- 15495142
TI  - Copper complex cation templated gadolinium(III)-isophthalate frameworks.

PMID- 15495143
TI  - Selected ion flow tube mass spectrometry (SIFT-MS) for on-line trace gas
      analysis.
AB  - Selected ion flow tube mass spectrometry (SIFT-MS) is a new analytical technique
      for the real-time quantification of several trace gases simultaneously in air and
      breath. It relies on chemical ionization of the trace gas molecules in air/breath
      samples introduced into helium carrier gas using H(3)O(+), NO(+), and O(2) (+.)
      precursor ions. Reactions between the precursor ions and trace gas molecules
      proceed for an accurately defined time, the precursor and product ions being
      detected and counted by a downstream mass spectrometer, thus effecting
      quantification. Absolute concentrations of trace gases in single breath
      exhalation can be determined by SIFT-MS down to ppb levels, obviating sample
      collection and calibration. Illustrative examples of SIFT-MS studies include (i)
      analysis of gases from combustion engines, animals and their waste, and food;
      (ii) breath and urinary headspace studies of metabolites, ethanol metabolism,
      elevated acetone during ovulation, and exogenous compounds; and (iii) urinary
      infection and the presence of tumors, the influence of dialysis on breath
      ammonia, acetone, and isoprene, and acetaldehyde released by cancer cells in
      vitro. Flowing afterglow mass spectrometry (FA-MS) is briefly described, which
      allows on-line quantification of deuterium in breath water vapor.

PMID- 15495144
TI  - A highly flexible dinuclear ruthenium(II)-platinum(II) complex: crystal structure
      and binding to 9-ethylguanine.

PMID- 15495146
TI  - Bioequivalence evaluation of two brands of amoxicillin/clavulanic acid 250/125 mg
      combination tablets in healthy human volunteers: use of replicate design
      approach.
AB  - The purpose of this study was to apply a replicate design approach to a
      bioequivalence study of amoxicillin/clavulanic acid combination following a
      250/125 mg oral dose to 23 subjects, and to compare the analysis of individual
      bioequivalence with average bioequivalence. This was conducted as a 2-treatment 2
      sequence 4-period crossover study. Average bioequivalence was shown, while the
      results from the individual bioequivalence approach had no success in showing
      bioequivalence. In conclusion, the individual bioequivalence approach is a strong
      statistical tool to test for intra-subject variances and also subject-by
      formulation interaction variance compared with the average bioequivalence
      approach.

PMID- 15495147
TI  - The bounds of the concentration index when the variable of interest is binary,
      with an application to immunization inequality.
AB  - When the health sector variable whose inequality is being investigated is binary,
      the minimum and maximum possible values of the concentration index are equal to
      micro-1 and 1-micro, respectively, where micro is the mean of the variable in
      question. Thus as the mean increases, the range of the possible values of the
      concentration index shrinks, tending to zero as the mean tends to one and the
      concentration index tends to zero. Examples are presented on levels of and
      inequalities in immunization across 41 developing countries, and on changes in
      coverage and inequalities in selected countries.

PMID- 15495148
TI  - State motor vehicle laws and older drivers.
AB  - After teenage males, elderly individuals have the highest per capita motor
      vehicle fatality rate in the United States. Surprisingly, there has been only
      limited work examining the effect of state motor vehicle laws on older driver
      fatalities. This paper uses state-level data from the 1985-2000 Fatality Analysis
      Reporting System to examine the effects of changes in state laws dealing with
      license renewal, seatbelt use, speed limits, and driving while intoxicated on
      fatalities among drivers and others aged 65 and over. Negative binomial
      regressions are estimated using alternatively state and year fixed effects, or
      age and year fixed effects. In-person license renewal reduced fatalities among
      the oldest drivers, but vision tests, road tests and the length of the license
      renewal cycle generally did not. In terms of policies that apply to all drivers,
      seatbelt laws, particularly with primary enforcement, were generally the only
      policies that reduced older driver fatalities. These results are noteworthy
      because a number of policies that have been effective towards increasing younger
      driver safety are not relevant for older drivers, implying that policymakers must
      think broadly about using state laws to improve older driver safety.

PMID- 15495149
TI  - Large-scale production of NbS(2) nanowires and their performance in electronic
      field emission.

PMID- 15495150
TI  - Synthesis of a bisubstrate-type inhibitor of N-acetylglucosaminyltransferases.

PMID- 15495151
TI  - Enantioselective synthesis of tetrafluoroethylene-containing monosaccharides.

PMID- 15495152
TI  - A cyclobutadiene equivalent in the catalytic Pauson-Khand reaction.

PMID- 15495153
TI  - Radical copolymerization of a phosphaalkene with styrene: new phosphine
      containing macromolecules and their use in polymer-supported catalysis.

PMID- 15495154
TI  - Preparation of Ag(2)S nanocrystals of predictable shape and size.

PMID- 15495155
TI  - Scandium-bipyridine-catalyzed enantioselective addition of alcohols and amines to
      meso-epoxides.

PMID- 15495156
TI  - A versatile aminobenzannulation method based on the deprotonation of 2-(1
      alkynyl)benzaldimines and similar 2-aza-2,4-heptadienyl-6-ynes: a multistep
      rearrangement cascade.

PMID- 15495157
TI  - Synthesis and functionalization of a new kind of silica particle.

PMID- 15495158
TI  - A stage-specific functional role of the leucine zipper transcription factor c-Maf
      in lung Th2 cell differentiation.
AB  - The transcription factor c-Maf controls IL-4 gene expression in CD4(+) T cells,
      and its expression is up-regulated in human asthmatic airways after allergen
      challenge. In the present study, we addressed the role of c-Maf in asthma by
      studying transgenic (Tg) mice overexpressing c-Maf in CD4(+) T cells under the
      control of the CD2 promoter. As shown, lung CD4(+) T cells of c-maf-Tg mice
      produced more IL-5 at the early stage (day 2) of culture in the presence of IL-4
      than wild-type control cells. Consistently, c-maf-Tg mice spontaneously showed
      increased IL-5 expression and eosinophils in the bronchial alveolar lavage fluid
      (BALF) and activated IL-5 signal transduction via Raf-1 and Ras in lung
      eosinophils. Finally, IL-13 was suppressed in the BALF of c-maf-Tg mice and in
      supernatants of Tg lung CD4(+) T cells cultured in the presence of IL-2.
      Consistently, retroviral overexpression of c-Maf suppressed IL-13 production in
      developing lung Th2 cells. In summary, c-Maf induces IL-5 production in lung
      CD4(+) T cells at an early stage, but along with IL-2 suppresses IL-13 production
      in differentiating lung Th2 cells, thereby explaining the finding that
      overexpression of c-Maf does not cause airway hyperresponsiveness, a hallmark
      feature of asthma.

PMID- 15495159
TI  - MHC class I-associated presentation of exogenous peptides is not only enhanced
      but also prolonged by linking with a C-terminal Lys-Asp-Glu-Leu endoplasmic
      reticulum retrieval signal.
AB  - Vaccination with antigenic peptide-pulsed antigen-presenting cells (APC)
      represents an attractive approach for therapy for cancer and diseases caused by
      intracellular infections. It has been suggested that sufficient stable
      MHC/peptide complexes on the surface of APC might play an important role in the
      generation of antitumor and antiviral immunity in vivo. In this study, we
      observed that exogenous peptides that were artificially fused with an endoplasmic
      reticulum (ER) retrieval signal, a C-terminal Lys-Asp-Glu-Leu sequence, could be
      efficiently presented by intracellular MHC class I molecules in a TAP- and
      proteasome-independent, but brefeldin A-sensitive manner. The APC retained the
      capacity to display surface MHC/peptide complexes for a prolonged period. In
      addition, our results show that vaccination with DC bearing our fusion peptides
      induced greatly enhanced specific CTL response, and resulted in significant
      inhibition of tumor growth. Thus, the ER retrieval signal modification can be
      regarded as a novel method for targeting exogenous peptides into the
      intracellular MHC class I presentation pathway, and may improve the clinical
      utility of vaccines based on synthetic peptide pulsed DC.

PMID- 15495160
TI  - Impaired B-1 and B-2 B cell development and atypical splenic B cell structures in
      IL-7 receptor-deficient mice.
AB  - The cytokine IL-7 and its receptor are essential for normal B and T
      lymphopoiesis. We have analyzed the role of this receptor in B cell development
      throughout ontogeny in IL-7 receptor alpha-deficient mice. We demonstrate that
      the IL-7 receptor becomes progressively more important with age. B lymphopoiesis
      takes place, albeit at reduced levels, in fetal liver and bone marrow of young
      mice, but is arrested in adults. The outcome is a severe reduction, from an early
      age, in peripheral B cells including follicular, marginal zone and B-1 B cells as
      well as perturbed splenic B cell structures, which are restored after adoptive
      transfer of normal spleen cells. We conclude that in the absence of the IL-7
      receptor, the residual B lymphopoiesis occurring early in ontogeny must be
      facilitated by another component, whereas the IL-7 receptor is the key factor in
      adults. The impairment of marginal zone and B-1 B cells in IL-7 receptor- but not
      IL-7-deficient mice suggests non-redundant functions for the IL-7 receptor
      ligands, IL-7 and thymic stromal lymphopoietin.

PMID- 15495161
TI  - Two-photon analysis of calcium signals in T lymphocytes of intact lamina propria
      from human intestine.
AB  - Lamina propria (LP) T cells of the human intestinal mucosa usually do not develop
      systemic immune responses despite permanent exposure to foreign antigens. The
      mechanisms maintaining this hyporeactivity in the normal gut are poorly
      understood. It is, at present, not clear what role the microenvironment of the
      mucosa plays for low T cell reactivity and in the pathogenesis of mucosal
      inflammation. Despite the importance of cytosolic Ca(2+) signals for T lymphocyte
      activation, intracellular Ca(2+) concentration measurements have so far only been
      performed in dissociated T cells, following disruption of the microenvironment.
      We used two-photon technology to measure Ca(2+) signals in identified T
      lymphocytes within the intact mucosa to minimize impact on tissue integrity while
      preserving the cellular microenvironment. We show that Ca(2+) signals in LP T
      cells correlate with the hyporeactivity of T cells in the intestinal immune
      system and furthermore link Ca(2+) signals with inflammatory bowel disease. Our
      data implicate that Ca(2+) signals in LP T cells do not depend on the
      microenvironment of the intact mucosa, since they are very similar to Ca(2+)
      signals in dissociated LP T cells.

PMID- 15495162
TI  - Mechanism of modulation of T cell responses by N-palmitoylated peptides.
AB  - Small structural changes in the antigenic peptides recognized by TCR can alter
      the biological properties of those peptides and convert them into weak agonists,
      partial agonists, or antagonists of these receptors. These altered peptide
      ligands (APL) are usually generated by conservative amino acid substitutions at
      TCR contact residues. Here, we show that APL with therapeutic properties can also
      be generated by attachment of palmitic acid at the N terminus of the peptide
      without the need to modify the peptide's primary sequence. Using N-palmitoylated
      pigeon cytochrome-c peptide 81-104 (PALPCC(81-104)), we were able to induce T
      cell hyporesponsiveness to the wild-type peptide in vitro. More importantly,
      administration of the PALPCC(81-104 )to mice reduced the responsiveness to the
      native peptide when tested ex vivo. Biochemical and functional experiments
      indicated that the action of N-palmitoylated peptides was due to the conversion
      of the native peptide into a weak agonist that could then induce T cell anergy.
      Our results demonstrate that N-palmitoylation of antigenic peptides is a feasible
      strategy to generate APL, as it avoids the need to screen multiple amino acid
      variants of each specific antigen to identify those with therapeutic properties.

PMID- 15495163
TI  - Monoclonal antibody to a DNA-binding domain of p53 mimics charge structure of
      DNA: anti-idiotypes to the anti-p53 antibody are anti-DNA.
AB  - Antibodies to DNA are important markers of various autoimmune diseases and can be
      pathogenic; however, their generation is not understood. We previously reported
      that anti-DNA antibodies could be induced in mice by idiotypic immunization to
      PAb-421, an antibody to a DNA-binding domain of p53. We now report that two
      monoclonal antibodies of moderate affinity (K(D) asymptotically equal to 10(-7)),
      raised from PAb-421-immunized mice, specifically recognized both PAb-421 and DNA.
      These antibodies feature multiple arginine residues in the antigen-binding site,
      a unique characteristic of disease-associated anti-DNA antibodies; nevertheless,
      these anti-DNA antibodies show specific complementarity to PAb-421 by competing
      with p53 for PAb-421 binding and recognize defined oligonucleotides with a
      specificity similar to that of p53. To study the structural basis for the cross
      recognition of PAb-421 and DNA by the anti-DNA antibodies, we constructed
      computer models (fine-tuned by protein-protein docking) of PAb-421 and one of the
      monoclonal anti-DNA antibodies. The modeled structures manifested structural
      complementarity. Most notably, the modeled structure of PAb-421 resembled the
      structure of DNA by the positions of negatively charged groups and aromatic side
      chains. Thus, a protein molecule may mimic the structure of DNA and the elusive
      generation of anti-DNA antibodies could be explained by idiotypic immunity to a
      DNA-binding protein, like p53.

PMID- 15495164
TI  - Aberrant B1 cell migration into the thymus results in activation of CD4 T cells
      through its potent antigen-presenting activity in the development of murine
      lupus.
AB  - B1 cells have different origin and function from conventional B (B2) cells and
      are considered to be involved in autoantibody production in the development of
      autoimmune disease. We found that B1 cells preferentially accumulated in the
      target organs including thymus in aged BWF1 mice, a murine model for systemic
      lupus erythematosus, and that B lymphocyte chemoattractant (BLC/CXCL13)
      expression was increased in the thymus before the onset of lupus nephritis, while
      stromal cell-derived factor-1 (SDF-1/CXCL12) and secondary lymphoid tissue
      chemokine (SLC/CCL21) expression remained unchanged. Adhesion molecules such as
      peripheral node addressin (PNAd), ICAM-1, and VCAM-1 were also expressed on
      endothelial cells in the enlarged thymic perivascular space (PVS) in aged BWF1
      mice. BLC protein and PNAd were co-localized on these high-endothelial-venules
      like vessels in enlarged PVS. B1 cells expressed higher level of costimulatory
      molecules and showed a potent antigen-presenting activity in allogeneic mixed
      lymphocyte reaction comparable to splenic dendritic cells. Interestingly, B1
      cells stimulated proliferation of autologous thymic CD4 T cells in the presence
      of IL-2. These results indicate that aberrant B1 cell trafficking into the thymus
      due to ectopic high expression of BLC may result in an activation of self
      reactive T cells in the development of murine lupus.

PMID- 15495165
TI  - Stratification of the flexor retinaculum and the course and distribution of the
      ulnar, median, and palmar digital nerves: an anatomical study.
AB  - A gross anatomic study of 169 hands from 94 human adult cadavers was carried out
      to define the morphology of the flexor retinaculum and the relationship of the
      flexor retinaculum to the course of the median and ulnar nerves and branching of
      the palmar digital nerves. The following results were obtained. Three parts of
      the flexor retinaculum were arranged like overlapping tiles on a roof, and in all
      cases, the median nerve passed deep to the flexor retinaculum, whereas the ulnar
      nerve passed through various parts of the flexor retinaculum in 19% of cases
      irrespective of its proximal form and branching of the palmar digital nerves.

PMID- 15495166
TI  - Unusual insertion of the coracobrachialis muscle to the brachial fascia
      associated with high division of brachial artery.
AB  - Anatomical variations of the coracobrachialis muscle (CBM) are common. We
      detected an abnormal form of the CBM of the left arm during human cadaver
      dissection. The CBM originated from the tip of the coracoid process of the
      scapula and divided into muscular and musculo-aponeurotic bellies. The muscular
      belly inserted into the middle of the anteromedial surface of the humerus, which
      is the normal anatomic insertion point of the CBM. The musculo-aponeurotic belly
      inserted into the medial intermuscular septum as well as the brachial fascia,
      creating a tunnel for the passage of the brachial artery. Inside the tunnel, the
      brachial artery bifurcated into the radial and ulnar arteries. No abnormality of
      the CBM, the brachial artery, or the median nerve was detected in the
      contralateral arm. The phylogenic, ontogenic, functional, and clinical importance
      of this variant muscle is described. Knowledge of such variations is of
      considerable importance during invasive and non-invasive investigative procedures
      or orthopedic, reconstructive, or surgical procedures.

PMID- 15495167
TI  - Attitudes of Turkish anatomists toward cadaver donation.
AB  - There is an insufficient number of cadavers in anatomy education in Turkey. This
      is because of decreased number of unclaimed bodies and very few cadaver
      donations. Increasing the number of cadaver donation is one of the probable
      solutions. Although anatomists encourage people to donate bodies, the attitudes
      of anatomists toward donating their own bodies for dissection is not well known.
      In this study, the attitudes of Turkish anatomists toward cadaver donation were
      evaluated. The questionnaires were sent to the anatomists in Turkey by mail and E
      mail. Eighty-three anatomists replied to the questionnaire. The main solutions
      proposed for cadaver insufficiency included increasing the supply of unclaimed
      bodies (77.1%) and increasing body donation (78.3%). Further, 51.8% of the
      respondents thought that increasing body donation was a long-term solution. The
      general belief (83.1%) was that a campaign would help to increase body donation
      and 47% of respondents were willing to participate in such a campaign. Of the 83
      anatomists, 20.5% of the respondents donated their organs and 49.4% were planning
      to donate them. Further, 15.7% were planning to donate their bodies; however,
      63.9% did not consider donating. The main reasons of the respondents to object
      the donation were: to be dissected by a colleague (15.7%), the unacceptability of
      donation by family (26.5%), psychological reasons (43.4%), the anxiety of
      disrespectful behavior to cadavers (26.5%), and religious beliefs (3.6%).
      Although the majority of the respondents objected to donating their bodies due to
      psychological reasons, body donation was proposed as the main solution of cadaver
      insufficiency.

PMID- 15495168
TI  - Imaging microscopy of the middle and inner ear: Part I: CT microscopy.
AB  - Anatomic definition of the middle ear and bony labyrinth in the clinical setting
      remains limited despite significant technological advances in computed tomography
      (CT). Recent developments in ultra-high resolution imaging for use in the
      research laboratory on small animals and pathologic specimens have given rise to
      the field of imaging microscopy. We have taken advantage of this technique to
      image a human temporal bone cadaver specimen to delineate middle ear and
      labyrinthine structures, only seen previously using standard light microscopy.
      This approach to the study of the inner ear avoids tissue destruction inherent in
      histological preparations. We present high-resolution MicroCT images of the
      middle ear and bony labyrinth to highlight the utility of this technique in
      teaching radiologists and otolaryngologists clinically relevant temporal bone
      anatomy. This study is not meant to function as a complete anatomic atlas of the
      temporal bone. We have selected several structures that are routinely delineated
      on clinical scanners to highlight the utility of imaging microscopy in displaying
      critical anatomic relationships in three orthogonal planes. These anatomic
      relationships can be further enhanced using 3D volume rendering.

PMID- 15495169
TI  - Prevalence of accessory head of flexor pollicis longus muscle and its relation to
      anterior interosseous nerve in Thai population.
AB  - A detailed description of the accessory head of flexor pollicis longus muscle
      (AHFPL) in the Thai population has not been reported. Because it is one of the
      causes of anterior interosseous nerve syndrome (AINS), a study was carried out on
      120 Thai cadavers (70 embalmed, 50 fresh; 78 male, 42 female) to elucidate the
      prevalence of AHFPL, its morphology and relationship with the anterior
      interosseous nerve (AIN). The prevalence of AHFPL was 62.1% (149/240) with 74.5%
      (111/149) of its origin on medial epicondyle, 23.5% (35/149) on coronoid process
      and 2% (3/149) on flexor digitorum superficialis muscle. One hundred percent of
      its insertion was on the ulnar border of flexor pollicis longus tendon, and it
      was 98% (146/149) fusiform-shaped and 2% (3/149) slender shaped, with a diameter
      between 0.8-16.0 mm (average 6.7 mm), averaging 6.5 mm on the right and 4.2 mm on
      the left. The right was significantly statistically larger than the left (P <
      0.05). The average distance from the mid-point of the distal wrist crease to the
      insertion point of AHFPL was 12.8 cm. Four patterns of relationship with AIN were
      noted including: 1) I AIN passed anterior to AHFPL, 13.4% (20/149); 2) AIN passed
      lateral to AHFPL, 65.8% (98/149); 3) AIN passed posterior to AHFPL, 8.1%
      (12/149); and 4) AIN passed both lateral and posterior to AHFPL, 12.8% (19/149).
      We believe that the latter two patterns (3 and 4) with AIN passing posteriorly
      would be more likely to be associated with AINS due to anatomic considerations.

PMID- 15495170
TI  - Anatomical study of perforator arteries in the distally based radial forearm
      fasciosubcutaneous flap.
AB  - We investigated the anatomical vascular basis of the forearm fasciosubcutaneous
      flap (FSC-F), fed by the distal perforator arteries of the fascia. This type of
      flap was proposed, in hand reconstructive surgery, to avoid the disadvantages
      caused by axial-pattern reverse radial forearm fasciocutaneous flap, based on
      ligation and rotation of the radial artery (RA). In eight fresh cadaveric
      forearms, the RA was injected slowly with acrylic resin and the superficial
      flexor compartment was dissected. Then the FSC-F was raised from the lateral
      margins of the sample to the median RA axis, and the collaterals of the RA
      (number, interval of origin, and caliber) were evaluated. The fascial branches of
      RA (mean number +/- SD: 20 +/- 3) originated mainly from the radial and ulnar
      sides of the RA. In the distal forearm the vessels were more numerous (mean value
      = 11.3 vs. 8.9; Student's t-test, P < 0.05) but smaller in diameter (mean value =
      0.45 mm vs. 0.63 mm; Student's t-test, P < 0.05). The perforator arteries forked
      in a T-shape following the main axis of the forearm and anastomosed in the
      fascial plane, forming longitudinal fan-shaped arterial chains giving rise to the
      vascular epifascial network. Histological (hematoxylin-eosin, azan-Mallory,
      Weigert) and immunohistochemical (anti-von Willebrand factor) study of the FSC-F
      at different levels of sampling was also carried out. The epifascial branches of
      distal sections were smaller in diameter (78.3 +/- 35.5 microm) than those of
      intermediate (105.7 +/- 28.7 microm; Newman-Keuls test, P < 0.01) and proximal
      (116.8 +/- 31.2 microm; Newman-Keuls test, P < 0.001) sections. Our findings
      indicate that the perforator arteries and epifascial branches are smaller in the
      distal forearm, so that during surgical dissection, the safety distance from the
      radial styloid should take into account that also in the presence of a sufficient
      number of vessels in the distal forearm their caliber could be inadequate to the
      hemodynamic request of the flap. Thus, rather than on a theoretic distance from
      the radial styloid, the length of the flap should be based on an accurate
      evaluation of the individual vascularization of the forearm case by case.

PMID- 15495171
TI  - Sir Felix Semon and Semon's law.

PMID- 15495172
TI  - Contributions of the hypoglossal nerve to the innervations of the recti capiti
      lateralis and anterior.
AB  - We dissected five Japanese cadavers (three males, two females) to investigate the
      innervations of the anterior vertebral muscles. According to our observations, it
      could be considered that the hypoglossal nerve would participates in the
      innervations of the recti capiti lateralis and anterior. In addition, we observed
      the small muscle bundle spanning between the recti capiti lateralis and anterior,
      which was not reported in previous studies as far as we know. This bundle
      received a branch of the hypoglossal nerve or the first cervical nerve. Based on
      the morphology and the innervation pattern, this bundle was considered to have
      close relationships with the recti capiti lateralis and anterior, especially with
      the former muscle.

PMID- 15495173
TI  - Triplication of the lesser occipital nerve.
AB  - Triplication of the lesser occipital nerve (LON) was observed bilaterally in an
      adult male cadaver during routine prosection of the posterior triangle. The three
      LONs were studied to determine the clinical importance of this variation. The
      origin of one LON was from a nerve to the trapezius that had a common origin with
      the trunk of the supraclavicular nerve (C3,4) from the cervical plexus. Such a
      common origin of a LON may explain the pain referred to the shoulder and arm that
      is experienced by some patients with cervicogenic headache. Another LON ran
      across the roof of the posterior triangle, passed through the trapezius and was
      closely related to the point of exit of the greater occipital nerve (GON) from
      the trapezius. This LON supplied the nape of the neck, back of the scalp and the
      auricle. The anomalous course taken by this LON through the trapezius may be an
      explanation for cervicogenic headache precipitated by neck movement. The close
      relationship of this variant LON to the exit of the GON from the trapezius seems
      to be relevant to the management of cervicogenic headache. The authors suggest
      that the reason for the complete pain relief experienced by some patients with
      cervicogenic headache by anesthetic blockade of the GON may be because both the
      GON and LON are blocked simultaneously due to their proximity in these patients.

PMID- 15495174
TI  - Reply to "Anatomy of renal arterial supply".

PMID- 15495175
TI  - Course of the short gastric veins and their suitability for pancreatic islet
      transplantation.
AB  - Experience is being gained with pancreatectomy for patients with chronic
      pancreatitis suffering intractable pain. Transplantation of pancreatic islets
      isolated from the patient's own pancreas reduces the amount of injected insulin
      required, and research aims to develop treatments to make such patients
      independent of administered insulin. Claims have been made that the uppermost
      short gastric vein runs directly to the upper pole of the spleen in about 90% of
      subjects and that infusion of pancreatic islets by this route would allow them to
      settle in the spleen. This study investigates these claims. The findings suggest
      that the short gastric veins are inappropriate as a route of islet
      administration. Most short gastric veins, including the most superior, drain to
      tributaries of the splenic vein. Short gastric veins passing to the spleen itself
      without extra-splenic connections to the splenic vein and its tributaries are
      relatively rare. Only four examples in 12 specimens were found, and only two of
      these were the most superior short gastric vein. The short gastric veins run in
      the fat of the gastrosplenic ligament and are most readily visible as they leave
      the stomach. In our 12 dissecting room specimens, the short gastric veins ranged
      in number from 3-17, and in diameter from 0.5-4.5 mm (mean = 1.7 mm; SD = 0.7
      mm). The four short gastric veins that drained directly to the spleen ranged in
      diameter from 0.5-1 mm, significantly narrower than those draining to the splenic
      vein or its tributaries and small for cannulation.

PMID- 15495176
TI  - "Hour-glass" shape of the uterus in the diagnosis and treatment of cervical
      pregnancy.
AB  - This study attempts to point out the importance of the anatomo-clinical finding
      of an "hour-glass" shape to the uterus in the diagnosis and treatment of cervical
      pregnancy. From 1973 to 2001, four cases of cervical pregnancy were treated in
      the 2nd Obstetrical and Gynecological Clinic of the Aristotelion University of
      Salonica. The incidence was 1:13,111 pregnancies (4 cervical in 52,446
      pregnancies). Three of the patients underwent bilateral ligation of the anterior
      trunk of the internal iliac artery using absorbable ligatures. The fourth patient
      (a 42-year-old), elected to have a hysterectomy. All patients were well and
      discharged from hospital on the seventh postoperative day. Two of the three
      patients treated by ligation of the anterior trunk of the internal iliac arteries
      subsequently had normal pregnancies and deliveries. We lost contact with the
      third patient. The finding of an "hour-glass" uterine shape was very helpful in
      the diagnosis of cervical pregnancy. The Aristotelion University of Salonica has
      found that treatment by ligation of the anterior trunk of the internal iliac
      arteries is effective, causes no complications, never ends in hysterectomy, and
      maintains the normal menstrual cycles and reproductive ability of the woman.

PMID- 15495178
TI  - Maxillary and sphenoid sinus aplasia in Turkish individuals: a retrospective
      review using computed tomography.
AB  - The absence of a maxillary or sphenoid sinus in an adult is an extremely rare
      condition. We investigated maxillary and sphenoid sinus aplasia in adult Turkish
      individuals using computed tomography (CT). We examined CT scans in the axial and
      coronal planes of the paranasal sinuses in 1,526 patients. The CT scans of a 21
      year-old male were notable for bilateral maxillary sinus aplasia. Another
      patient, a 20-year-old female, had CT scans that showed the unilateral absence of
      a maxillary sinus. Two additional cases showed the unilateral absence of one
      sphenoid sinus. Bilateral absence of the sphenoid sinuses was not observed in our
      study. The clinical implications of maxillary and sphenoid sinus aplasia will be
      further discussed.

PMID- 15495177
TI  - Inverse association between prostatic polyunsaturated fatty acid and risk of
      locally advanced prostate carcinoma.
AB  - BACKGROUND: An effect of fatty acids has been implicated in men with advanced
      stage prostate carcinoma and in men who have died of the disease. To evaluate the
      influence of fatty acids in men with prostate carcinoma at earlier stages, the
      authors examined the relation between prostatic concentrations of fatty acids and
      locally advanced prostate carcinoma in men with clinically organ-confined
      disease. METHODS: Fatty acids were measured by capillary gas chromatography in
      fresh, nonmalignant prostate tissue specimens collected during surgery from 196
      men undergoing radical prostatectomy for localized prostate carcinoma. Two-sided,
      two-sample Student t tests compared mean concentrations in men with
      extraprostatic disease (pT3-4N0-1M0) with control men with organ-confined
      disease. Logistic regression accounted for clinical stage, prostate-specific
      antigen level, Gleason sum, and other factors. RESULTS: Percent total prostatic
      polyunsaturated fatty acid (PUFA) was found to be inversely associated with risk
      of locally advanced prostate carcinoma (n=52) (odds ratio [OR]=0.93, 95%
      confidence interval [95% CI], 0.87-0.99; P=0.035). Risk of seminal vesicle
      involvement accounted for this association (OR=0.86, 95% CI, 0.78-0.95; P=0.003).
      Percent omega-3 fatty acid (eicosapentanoic + docosahexanoic acids) and percent
      arachidonic acid also were found to be inversely related to the risk of seminal
      vesicle involvement (OR=0.52, 95% CI, 0.30-0.90; P=0.02; and OR=0.84, 95% CI,;
      0.75-0.95; P=0.005, respectively). CONCLUSIONS: Prostatic PUFA levels appear to
      influence the risk of locally advanced prostate carcinoma in men with clinically
      organ-confined disease. This association may be mediated through the immune
      system.

PMID- 15495179
TI  - Synthesis and endosomolytic properties of poly(amidoamine) block copolymers.
AB  - The poly(amidoamine)s (PAAs) ISA 1 and ISA 23 display pH-dependent conformational
      change and pH-dependent membrane perturbation. These properties confer potential
      for use as endosomolytic polymers for intracytoplasmic delivery of toxins and
      genes. Both polymers are relatively non-toxic, and moreover ISA 23 has the
      beneficial property in vivo, of being non hepatotropic when administered
      intravenously. Although ISA 23 and ISA 1 demonstrate ability to transfect cells,
      ISA 1 is also able to promote intracellular delivery of non-permeant toxins. The
      aim of this study was to synthesise random and block copolymers of ISA 1 and ISA
      23 and investigate whether these second generation hybrids would allow
      optimisation of PAA biological characteristics. Random and block copolymers of
      ISA 1 and ISA 23 were synthesised by hydrogen transfer polyaddition to generate a
      library of PAAs with an ISA 23:ISA 1 molar ratios of 2:1 to 4:1. The resultant
      polymers have a pI slightly below 7.4 and a M(w) of 19,900-49,000 g/mol and a
      M(n) of 13,100-24,100 g/mol. Whereas none of the random or block copolymers were
      haemolytic at pH 7.4 all demonstrated pH-dependent membrane activity. At pH 5.5
      they caused 50-60% haemoglobin (Hb) release over 1 h. This was slightly less than
      that seen for ISA 23 (80% Hb release). None of the copolymers were cytotoxic
      against B16F10 cells during a 72 h incubation (IC(50) > 2 mg/ml; MTT assay). The
      ability of the random and block copolymer PAAs to deliver the toxin gelonin was
      also examined, but only ISA 1 and the block copolymer B2 (ISA 23:ISA 1 at a 2:1
      molar ratio) were able to promote intracellular delivery, as measured by
      cytotoxic activity. It would be interesting to study the body distribution of B2
      and determine whether this toxin-delivering PAA is able to escape liver capture.

PMID- 15495180
TI  - A tool for predicting breast carcinoma mortality in women who do not receive
      adjuvant therapy.
AB  - BACKGROUND: Among the several proposed risk classification schemes for predicting
      survival in women with breast carcinoma, one of the most commonly used is the
      Nottingham Prognostic Index (NPI). The goal of the current study was to use a
      continuous prognostic model (similar to those that have already been demonstrated
      to possess greater predictive accuracy than risk group-based models in other
      malignancies) to predict breast carcinoma mortality more accurately compared with
      the NPI. METHODS: A total of 519 women who had been treated with mastectomy and
      axillary lymph node dissection at Memorial Sloan-Kettering Cancer Center (New
      York, NY) between 1976 and 1979 met the following requirements for study
      inclusion: confirmation of the presence of invasive mammary carcinoma, no receipt
      of neoadjuvant or adjuvant systemic therapy, no previous history of malignancy,
      and negative lymph node status as assessed on routine histopathologic
      examination. Paraffin blocks were available for 368 of the 519 eligible patients.
      All available axillary lymph node tissue blocks were subjected to enhanced
      pathologic analysis. The competing-risk method was used to predict disease
      specific death, and the accuracy of the novel prognostic model that emerged from
      this process was evaluated using the concordance index. Jackknife and 10-fold
      cross-validation predictions yielded by this new model were compared with
      predictions yielded by the NPI. RESULTS: Of the 348 women for whom complete data
      were available, 73 died of disease; the 15-year probability of breast carcinoma
      related death was 20%. On the basis of these 348 cases, the authors developed a
      prognostic model that took patient age, disease multifocality, tumor size, tumor
      grade, lymphovascular invasion, and enhanced lymph node staining into account,
      and using competing-risks regression analysis, they found that this new model
      predicted disease-specific death more accurately compared with the NPI.
      CONCLUSIONS: The authors have developed a model for predicting breast carcinoma
      specific death with improved accuracy. This tool should be useful in counseling
      patients with regard to their specific need for adjuvant therapy.

PMID- 15495181
TI  - Carcinoid metastasis to the brain.
AB  - BACKGROUND: Carcinoid tumors rarely metastasize to the brain. The objectives of
      the current study were to assess the frequency of brain metastasis from carcinoid
      tumors, determine correlates of survival, and describe treatment modalities and
      their outcomes. METHODS: Between January 1977 and December 2003, 1633 patients
      with a carcinoid tumor were registered at The University of Texas M. D. Anderson
      Cancer Center. Of those, 24 patients (1.5%) had a diagnosis of brain metastasis.
      The authors collected demographic and clinical data and performed a statistical
      analysis. RESULTS: The median age at the time patients were diagnosed with brain
      metastasis was 60 years. The metastases were treated with whole-brain
      radiotherapy (WBRT) alone in 7 patients (29%), and 12 patients (50%) underwent
      surgical resection, 7 of whom (29%) also received WBRT. The median survival time
      for the entire cohort after diagnosis of the primary tumor was 2.3 years (95%
      confidence interval [CI], 0.5-4.1 years), and the median survival time after the
      diagnosis of brain metastasis was 10.0 months (95% CI, 4.0-16.0 months). The
      longest median survival observed after the diagnosis of brain metastasis (3.2
      years) occurred in patients who underwent resection and received WBRT. In the
      multivariate analysis, the adjusted rate ratio for comparison of all treatments
      versus combination of neurosurgical intervention and WBRT was 5.7 (95% CI, 1.3
      26.1; P = 0.024). A positive effect of surgery followed by WBRT on the duration
      of survival was detected in patients with a single metastasis (P = 0.084) as well
      as in those with multiple metastases (P = 0.018). CONCLUSIONS: Prolonged survival
      was observed in patients < 65 years old as well as in those who underwent surgery
      and received WBRT in comparison with other treatments. Whenever feasible,
      neurosurgical resection followed by WBRT seems to be the indicated treatment in
      patients with brain metastases from carcinoid tumors.

PMID- 15495182
TI  - Dynamic imaging of cell, extracellular matrix, and tissue movements during avian
      vertebral axis patterning.
AB  - Vertebrate axis patterning depends on cell and extracellular matrix (ECM)
      repositioning and proper cell-ECM interactions. However, there are few in vivo
      data addressing how large-scale tissue deformations are coordinated with the
      motion of local cell ensembles or the displacement of ECM constituents. Combining
      the methods of dynamic imaging and experimental biology allows both cell and ECM
      fate-mapping to be correlated with ongoing tissue deformations. These fate
      mapping studies suggest that the axial ECM components "move" both as a composite
      meshwork and as autonomous particles, depending on the length scale being
      examined. Cells are also part of this composite, and subject to passive
      displacements resulting from tissue deformations. However, in contrast to the
      ECM, cells are self-propelled. The net result of cell and ECM displacements,
      along with proper ECM-cell adhesion, is the assembly of new tissue architecture.
      Data herein show that disruption of normal cell-ECM interactions during axis
      formation results in developmental abnormalities and a disorganization of the
      ECM. Our goal in characterizing the global displacement patterns of axial cells
      and ECM is to provide critical information regarding existing strain fields in
      the segmental plate and paraxial mesoderm. Deducing the mechanical influences on
      cell behavior is critical, if we are to understand vertebral axis patterning.
      Supplementary material for this article is available online at
      http://www.mrw.interscience.wiley.com/suppmat/1542-975X/suppmat/72/v72.266.html.

PMID- 15495183
TI  - In vivo biofluid dynamic imaging in the developing zebrafish.
AB  - Flow-structure interactions are ubiquitous in nature, and are important factors
      in the proper development of form and function in living organisms. In order to
      uncover the mechanisms by which flow-structure interactions affect vertebrate
      development, we first need to establish the techniques necessary to
      quantitatively describe the fluid flow environment within the embryo. To do this,
      we must bring dynamic, in vivo imaging methods to bear on living systems.
      Traditional avian and mammalian model systems can be problematic in this regard.
      The zebrafish (Danio rerio) is widely accepted as an excellent model organism for
      the study of vertebrate biology, as it shows substantial anatomical and genetic
      conservation with higher vertebrates, including humans. Their small size, optical
      transparency, and external development make zebrafish the ideal model system for
      dynamic imaging. This article reviews the current state of research in imaging
      biofluid flow within and around developing zebrafish embryos, with an emphasis on
      dynamic imaging modalities.

PMID- 15495184
TI  - Developmental imaging: Insights into the avian embryo.
AB  - The study of embryonic events using different animal model systems is crucial for
      gaining insights into human development and birth defects. Biological imaging
      plays a major role in this effort by providing a spatiotemporal framework to link
      complex cell movements with molecular data. However, depending on the age of the
      embryo and the location of a morphogenetic event, visualization often requires
      the design of novel culture and imaging techniques. One of the primary model
      systems for biological imaging is the avian embryo, due to its accessibility to
      manipulation, relatively two-dimensional morphogenesis early on, and viability
      when grown in culture. Significant work in avian embryo culture and cell
      labeling, together with advances in imaging technology, now make it possible to
      monitor many developmental events within the period from egg laying to hatching.
      Here, we present the latest in avian developmental imaging, focusing on cell
      labeling, embryo culture, and imaging technologies.

PMID- 15495185
TI  - Making the mouse embryo transparent: identifying developmental malformations
      using magnetic resonance imaging.
AB  - Developmental malformations are a major cause of childhood mortality and are
      typically characterized by lesions that allow survival of the embryo through
      gestation. The genetics of developmental malformations are powerfully studied by
      using high-throughput, phenotype-driven screens (e.g., following zebrafish or
      mouse mutagenesis) or by genotype-driven studies using transgenic or knockout
      mice. With regard to either approach, the mouse is anatomically and
      phylogenetically closer to humans than any other genetically tractable model
      organism. This is particularly important in the cardiovascular and respiratory
      systems, which have unique mammalian features. The identification of murine
      models of developmental malformations is, however, hindered by the opacity of the
      late gestational mouse embryo. In this review, we describe recent advances in
      magnetic resonance imaging that make it possible to rapidly identify
      malformations in the developing mouse embryo with high efficiency.

PMID- 15495186
TI  - Molecular imaging of the embryonic heart: Fables and facts on 3D imaging of gene
      expression patterns.
AB  - Molecular imaging, which is the three-dimensional (3D) visualization of gene
      expression patterns, is indispensable for the study of the function of genes in
      cardiac development. The instrumentation, as well as the development of specific
      contrast agents for molecular imaging, has shown spectacular advances in the last
      decade. In this review, the spatial resolutions, contrast agents, and
      applications of these imaging methods in the field of cardiac embryology are
      discussed. Apart from 3D reconstructions from histological sections, not many of
      these methods have been applied in embryological research. This review shows
      that, for most methods, neither the spatial resolutions nor the specificity and
      applicability of the contrast agents are adequate for the reliable imaging of
      specific gene expression at the microscopic resolution required for embryological
      studies of small organs like the developing heart. Although a 3D reconstruction
      from sections will always suffer from imperfections, the resulting
      reconstructions meet the aim of most biological studies, especially since the
      original microscopic images are linked. With respect to imaging of gene
      expression, only histological sections and laser scanning microscopy provide the
      required resolution and specificity at the tissue and cellular level. Episcopic
      fluorescence image capturing and optical projection tomography are being used for
      microscopic phenotyping and lineage analysis, and both show potential for
      detailed molecular imaging. Other methods can be used very efficiently in rapid
      evaluation of biological experiments and high-throughput screens of large-scale
      gene expression profiling efforts when high spatial resolution is not required.

PMID- 15495187
TI  - Microcomputed tomography imaging of skeletal development and growth.
AB  - Skeletogenesis is an exquisitely orchestrated and dynamic process, culminating in
      the formation of highly variable and complex mineralized structures that are
      optimized for their function. While cellular and molecular biology studies have
      provided tremendous recent progress toward understanding how patterns of bone
      formation are regulated, high resolution imaging techniques such as microcomputed
      tomography (micro-CT) can provide complementary quantitative information about
      the progressive changes in three-dimensional (3-D) skeletal morphology and
      density that occur during early skeletal development and postnatal growth.
      Furthermore, recently developed in vivo micro-CT systems promise to be a powerful
      and efficient tool for noninvasively monitoring normal skeletogenesis, as well as
      for evaluating the effects of genetic or environmental manipulation. This review
      focuses on the use of micro-CT imaging and analysis to better understand normal
      and abnormal skeletal development and growth.

PMID- 15495188
TI  - Rapid high resolution three dimensional reconstruction of embryos with episcopic
      fluorescence image capture.
AB  - One of the overarching goals in developmental biology is the elucidation of
      mechanisms that elaborate form and function. To this end, an accurate
      morphological description of embryonic development is essential. However,
      visualizing dynamic changes in the three-dimensional (3D) structure of the
      developing embryo has been a "holy grail" in the field of developmental biology.
      The fundamental difficulties that have hindered all efforts in 3D reconstruction
      using two-dimensional (2D) image stacks revolve around the seemingly intractable
      problems of section registration and distortion. A remarkably simple solution has
      come about with the development of a new technique referred to as episcopic
      fluorescence image capture (EFIC). With EFIC imaging, tissue autofluorescence is
      used to image the block face prior to cutting each section. The 2D resolution
      obtained is close to that achieved by histology, and such 2D image stacks can be
      readily reconstructed in 3D. The 3D models generated provide fine structural
      details with resolution unmatched by 3D reconstructions obtained with any other
      imaging modalities. Given the perfect registration of EFIC image stacks, another
      important capability provided by EFIC is digital resectioning in any plane. This
      provides complete flexibility in the selection of optimal virtual sectioning
      planes for viewing different features in a specimen, and is invaluable for
      analyzing dynamic changes in tissue structure in the developing embryo. The
      capabilities provided by EFIC for rapid high resolution 3D reconstruction
      together with digital resectioning make this an unparalleled tool for
      characterizing morphogenetic events in the developing embryo. Although our review
      is focused on using EFIC for studying embryonic development, it is important to
      note that there is no intrinsic limitation on the size of the specimen that can
      be analyzed by EFIC imaging. Overall, EFIC should serve as an important imaging
      technique that will complement other 3D imaging modalities such as MRI and
      optical tomography. Given the feasibility of generating EFIC image stacks using
      cryoembedded or polyethylene glycol (PEG)-embedded specimens, there is the
      possibility that EFIC may be combined with 3D RNA or protein expression
      profiling. Together, such studies may help further elucidate the relationship
      between form and function.

PMID- 15495192
TI  - Frequent deletions at 12q14.3 chromosomal locus in adult acute lymphoblastic
      leukemia.
AB  - Cytogenetic abnormalities at the 12q12-q14 chromosomal locus are rarely detected
      in acute lymphoblastic leukemia (ALL). To examine submicroscopic deletions at
      this locus, we analyzed 78 adult precursor B- and T-cell ALL cases [27 with
      Philadelphia chromosome (Ph)-negative B-cell ALL, 20 with Ph-negative B-cell ALL
      with expression of one or two myeloid markers, 18 with Ph-positive B-cell ALL,
      and 13 with T-cell ALL] using a panel of 13 microsatellite (MST) markers that
      span the 12q12-q14.3 region. The status of MST markers was evaluated by use of
      polymerase chain reaction performed with fluorescence-labeled primers and
      automated fragment analysis. The MST marker analyses showed submicroscopic
      deletions at the 12q14.3 locus in 20 of the 78 ALL cases (26%). The frequency of
      deletions was highest in Ph-negative B-cell ALL (13 of 27, 48%) compared with
      that in Ph-negative B-cell ALL with expression of myeloid markers (4 of 20, 20%),
      Ph-positive B-cell ALL (2 of 18, 11%), and T-cell ALL (1 of 13, 8%). Deletion
      frequencies of MST markers along the 12q12-q14.3 locus suggest that the targeted
      gene of deletion is located within a 170-kb region bordered by the markers
      D12S1504 (approximately 65 kb upstream of HMGA2) and D12S1509 (in intron 3 of
      HMGA2) at the 12q14.3 locus. These submicroscopic deletions at the 12q14.3 locus
      may play a role in the pathogenesis of ALL, particularly in Ph-negative precursor
      B-cell ALL.

PMID- 15495191
TI  - Homozygous deletions of CDKN2A caused by alternative mechanisms in various human
      cancer cell lines.
AB  - The CDKN2A tumor-suppressor locus on chromosome band 9p21, which encodes
      p16(INK4A), a negative regulator of cyclin-dependent kinases, and p14(ARF1), an
      activator of TP53, is inactivated in many human cancers by point mutation,
      promoter hypermethylation, and, often, deletion. Homozygous deletions are
      unusually prevalent at this locus in very different human cancers. In the present
      study, we compared deletions in squamous cell carcinoma of the head and neck
      (SCCHN) cell lines to those in T-cell acute lymphatic leukemia (T-ALL), glioma,
      and bladder carcinoma (TCC) cell lines. Of 14 SCCHN lines, 10 showed homozygous
      deletions of CDKN2A, one displayed promoter hypermethylation with gene silencing,
      and one had a frameshift deletion in exon 2. Many deletion ends were in or
      proximal to the repetitive sequence clusters flanking the locus. Breakpoint
      junctions displayed variable microhomologies or insertions characteristic of DNA
      repair by nonhomologous end-joining. In general, deletions were much smaller in
      SCCHN than in TCC and glioma. In T-ALL, breakpoints were near consensus sites for
      recombination mediated by RAG (recombination activating genes) enzymes, and the
      structure of the junctions was consistent with this mechanism. We suggest that
      different mechanisms of CDKN2A deletion prevail in different human cancers.
      Aberrant RAG-mediated recombination may be responsible in T-ALL, and exuberant
      DNA repair by nonhomologous end-joining is the likely prevailing mechanism in
      SCCHN, but a distinct mechanism in TCC and glioma remains to be elucidated.

PMID- 15495193
TI  - Computer-generated high-valent iron--oxo and manganese--oxo species with
      polyoxometalate ligands: how do they compare with the iron--oxo active species of
      heme enzymes?

PMID- 15495195
TI  - Prions: proof of proteinaceous nature but problems with population polymorphisms.

PMID- 15495196
TI  - Prospects for the development of pre-mortem laboratory diagnostic tests for
      Creutzfeldt-Jakob disease.
AB  - At present the diagnosis of Creutzfeldt-Jakob disease (CJD) and related
      transmissible spongiform encephalopathies in humans is based on clinical criteria
      and (at post-mortem) the histopathological and immunological examination of brain
      tissue. The misfolded prion protein, PrPSc, is the single most significant
      marker, but its recognition by standard serological methods is complicated by its
      antigenic similarity to the normal prion protein, PrPC. Although there are
      commercial diagnostic assays available for bovine spongiform encephalopathy using
      brain specimens taken at slaughter, there are no suitable pre-mortem assays for
      cattle and none either for pre-mortem human disease. Especially in view of the
      recent report of variant CJD transmission by blood transfusion, it is important
      that tests for pre-symptomatic infections are developed. This will safeguard the
      blood supply and, for example, prevent the transmission of CJD in neurosurgery.
      This paper reviews the current and prospective approaches to the pre-mortem
      diagnosis of CJD, in particular its variant form.

PMID- 15495197
TI  - Cytogenetic manifestations of multiple myeloma heterogeneity.
AB  - To investigate the genetic basis of the great heterogeneity observed in the
      clinical behavior of multiple myeloma (MM), a combined approach of G-banding,
      interphase fluorescence in situ hybridization (FISH), and multicolor FISH (M
      FISH) was employed to analyze 70 samples from 53 patients with MM. G-banding
      revealed abnormal karyotypes in 77% of the cases. The origin of 31 chromosome
      markers was identified or revised by M-FISH. Combined metaphase karyotypic data
      and interphase FISH findings, using the immunoglobulin heavy-chain (IGH),
      IGH/cyclin D1 gene (CCND1), and D13S319 probes, revealed chromosome abnormalities
      in all evaluated patients and marked inter- and intratumor cytogenetic
      heterogeneity in the investigated MM samples. Cytogenetically unrelated clones
      were detected in 26% of the cases, mostly MM evaluated at diagnosis, whereas
      cytogenetic clonal evolution, manifested as related clones in 20% of the cases,
      was associated with disease progression. Among the 14q32 rearrangements, present
      in 66% of the cases, at least three cytogenetic subsets could be identified: one
      with t(11;14), usually without 13q14 deletion; another with other IGH changes,
      often 13q14 deletion, and hypodiploid modal chromosome number; and a third
      without changes in 14q32 but with abnormalities of chromosome 17. The correlation
      found between cytogenetic and clinicopathologic characteristics provided support
      for the concept that general genomic features in conjunction with specific
      chromosome rearrangements define the malignant phenotype in the various subsets
      of MM.

PMID- 15495198
TI  - Discrete breakpoint mapping and shortest region of overlap of chromosome arm 1q
      gain and 1p loss in human hepatocellular carcinoma detected by semiquantitative
      microsatellite analysis.
AB  - Recurrent chromosomal gain at 1q is one of the most common features of human
      hepatocellular carcinoma (HCC), but how the gain at 1q contributes to
      hepatocarcinogenesis is still unclear. To identify the target genes, precise
      determination of the shortest region of overlap (SRO) and of breakpoints is
      necessary. Similarly, the role of loss at 1p, which is also a major cytogenetic
      aberration in HCC, needs to be determined. Fifty HCCs were examined with the aid
      of 59 microsatellite markers distributed throughout both arms of chromosome 1. To
      detect allelic gain effectively, the cutoff value of the allelic imbalance index
      was set at 0.70. Alleles showing imbalance were subjected to multiplex PCR, using
      a retained allele as an internal control, to determine whether the imbalance was
      the result of chromosomal gain or loss. The SRO of the gains was defined as
      D1S2878-D1S2619 (1q23.-q25.3, 16.9 Mb), which involved 36 cases (72%). Gains in
      the number of copies of certain oncogenes within this region seemed to be
      critical for the pathogenesis of HCC. In contrast, the centromeric breakpoints of
      these gains varied, but they tended to occur mainly in the pericentromeric region
      (26 of 50 cases, 52%). Rearrangement of specific genes associated with the gains
      is unlikely. On the other hand, the SRO of deletion was defined as D1S2893-D1S450
      (1p36.32-p36.22, 5.1 Mb). Four known putative tumor-suppressor genes (TP73, RIZ1,
      NBL1/DAN, and CDKN2C) were outside the SRO, suggesting the presence of other
      candidate genes with critical roles in hepatocarcinogenesis.

PMID- 15495199
TI  - Human prostate cancer risk factors.
AB  - Prostate cancer has the highest prevalence of any nonskin cancer in the human
      body, with similar likelihood of neoplastic foci found within the prostates of
      men around the world regardless of diet, occupation, lifestyle, or other factors.
      Essentially all men with circulating androgens will develop microscopic prostate
      cancer if they live long enough. This review is a contemporary and comprehensive,
      literature-based analysis of the putative risk factors for human prostate cancer,
      and the results were presented at a multidisciplinary consensus conference held
      in Crystal City, Virginia, in the fall of 2002. The objectives were to evaluate
      known environmental factors and mechanisms of prostatic carcinogenesis and to
      identify existing data gaps and future research needs. The review is divided into
      four sections, including 1) epidemiology (endogenous factors [family history,
      hormones, race, aging and oxidative stress] and exogenous factors [diet,
      environmental agents, occupation and other factors, including lifestyle
      factors]); 2) animal and cell culture models for prediction of human risk (rodent
      models, transgenic models, mouse reconstitution models, severe combined
      immunodeficiency syndrome mouse models, canine models, xenograft models, and cell
      culture models); 3) biomarkers in prostate cancer, most of which have been tested
      only as predictive factors for patient outcome after treatment rather than as
      risk factors; and 4) genotoxic and nongenotoxic mechanisms of carcinogenesis. The
      authors conclude that most of the data regarding risk relies, of necessity, on
      epidemiologic studies, but animal and cell culture models offer promise in
      confirming some important findings. The current understanding of biomarkers of
      disease and risk factors is limited. An understanding of the risk factors for
      prostate cancer has practical importance for public health research and policy,
      genetic and nutritional education and chemoprevention, and prevention strategies.

PMID- 15495200
TI  - Factors associated with complex visual hallucinations during antidepressant
      treatment.
AB  - Published case reports on complex visual hallucinations (CVH) occurring during
      antidepressant (AD) treatment were reviewed. Thirteen cases of CVH associated
      with SSRI treatment, 16 cases during tricyclic drug treatment and seven cases
      with other AD drug treatments were found. Nine patients were taking concomitant
      drugs while on therapy with SSRIs and four had a neurological disease in addition
      to depression. The cholinergic impoverishment occurring in dementia states or
      during concomitant therapy with anticholinergic drugs could increase the
      sensitivity to serotonergic agonists, triggering the manifestation of CVH. During
      tricyclic drug treatment, half of the reports were of hypnopompic or hypnagogic
      hallucinations and this can be associated with the effects of tricyclics (TCA) on
      sleep architecture. It is likely that the potent anticholinergic effect of
      amitriptyline was potentiated in a situation of a rapidly changing state of
      consciousness. In general, the review supports the view that an imbalance between
      serotonin and acetylcholine systems is at the root of AD-induced CVH, with a
      profile defined by a cholinergic hypoactivity and a serotonergic hyperactivity.
      Caution is needed when administering a combination of serotonergic and
      anticholinergic AD in the treatment of the demented population and in other
      already compromised patients because there is a risk of precipitating CVH.

PMID- 15495201
TI  - Drosophila tudor is essential for polar granule assembly and pole cell
      specification, but not for posterior patterning.
AB  - Pole cells and posterior segmentation in Drosophila are specified by maternally
      encoded genes whose products accumulate at the posterior pole of the oocyte.
      Among these genes is tudor (tud). Progeny of hypomorphic tud mothers lack pole
      cells and have variable posterior patterning defects. We have isolated a null
      allele to further investigate tud function. While no pole cells are ever observed
      in embryos from tud-null mothers, 15% of these embryos have normal posterior
      patterning. OSKAR (OSK) and VASA (VAS) proteins, and nanos (nos) RNA, all
      initially localize to the pole plasm of tud-null oocytes and embryos from tud
      null mothers, while localization of germ cell-less (gcl) and polar granule
      component (pgc), is undetectable or severely reduced. In embryos from tud-null
      mothers, polar granules are greatly reduced in number, size, and electron
      density. Thus, tud is dispensable for somatic patterning, but essential for pole
      cell specification and polar granule formation.

PMID- 15495202
TI  - Isolation and structure of an "imploded" cryptophane.

PMID- 15495203
TI  - Design of a modular-based fluorescent conjugated polymer for selective sensing.

PMID- 15495204
TI  - Directing self-assembly of nanoparticles at water/oil interfaces.

PMID- 15495205
TI  - Design and synthesis of photochemically controllable caspase-3.

PMID- 15495206
TI  - Magnetically separable, carbon-supported nanocatalysts for the manufacture of
      fine chemicals.

PMID- 15495207
TI  - Calibrated calculation of polyalanine fractional helicities from circular
      dichroism ellipticities.

PMID- 15495209
TI  - Synthesis and characterization of a directly linked N-confused porphyrin dimer.

PMID- 15495208
TI  - Micrometer-sized spherical assemblies of polypeptides and small molecules by acid
      base chemistry.

PMID- 15495210
TI  - 3,6-Di(azido)-1,2,4,5-tetrazine: a precursor for the preparation of carbon
      nanospheres and nitrogen-rich carbon nitrides.

PMID- 15495211
TI  - Projections from the trigeminal nuclear complex to the cochlear nuclei: a
      retrograde and anterograde tracing study in the guinea pig.
AB  - In addition to input from auditory centers, the cochlear nucleus (CN) receives
      inputs from nonauditory centers, including the trigeminal sensory complex. The
      detailed anatomy, however, and the functional implications of the nonauditory
      innervation of the auditory system are not fully understood. We demonstrated
      previously that the trigeminal ganglion projects to CN, with terminal labeling
      most dense in the marginal cell area and secondarily in the magnocellular area of
      the ventral cochlear nucleus (VCN). We continue this line of study by
      investigating the projection from the spinal trigeminal nucleus to CN in guinea
      pig. After injections of the retrograde tracers FluoroGold or biotinylated
      dextran amine (BDA) in VCN, labeled cells were found in the spinal trigeminal
      nuclei, most densely in the pars interpolaris and pars caudalis with ipsilateral
      dominance. The anterograde tracers Fluoro-Ruby or BDA were stereotaxically
      injected into the spinal trigeminal nucleus. Most labeled puncta were found in
      the marginal area of VCN and the fusiform cell layer of dorsal cochlear nucleus
      (DCN). A smaller number of labeled puncta was located in the molecular and deep
      layers of DCN and the magnocellular area of VCN. The trigeminal projection to CN
      may provide somatosensory information necessary for pursuing a sound source or
      for vocal production. These projections may have a role in the generation and
      modulation of tinnitus.

PMID- 15495213
TI  - The first all-cyanide Fe(4)S(4) cluster: [Fe(4)S(4)(CN)(4)](3-).

PMID- 15495212
TI  - Each sensory nerve arising from the geniculate ganglion expresses a unique
      fingerprint of neurotrophin and neurotrophin receptor genes.
AB  - Neurons in the geniculate ganglion, like those in other sensory ganglia, are
      dependent on neurotrophins for survival. Most geniculate ganglion neurons
      innervate taste buds in two regions of the tongue and two regions of the palate;
      the rest are cutaneous nerves to the skin of the ear. We investigated the
      expression of four neurotrophins, nerve growth factor (NGF), brain-derived
      neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and NT-4, and five
      neurotrophin receptors, trkA, trkB, trkC, p75, and truncated trkB (Trn-B) in
      single sensory neurons of the adult rat geniculate ganglion associated with the
      five innervation fields. For fungiform papillae, a glass pipette containing
      biotinylated dextran was placed over the target papilla and the tracer was
      iontophoresed into the target papilla. For the other target fields, Fluoro-Gold
      was microinjected. After 3 days, geniculate ganglia were harvested, sectioned,
      and treated histochemically (for biotinylated dextran) or immunohistochemically
      (for Fluoro-Gold) to reveal the neurons containing the tracer. Single labeled
      neurons were harvested from the slides and subjected to RNA amplification and RT
      PCR to reveal the neurotrophin or neurotrophin receptor genes that were
      expressed. Neurons projecting from the geniculate ganglion to each of the five
      target fields had a unique expression profile of neurotrophin and neurotrophic
      receptor genes. Several individual neurons expressed more than one neurotrophin
      receptor or more than one neurotrophin gene. Although BDNF is significantly
      expressed in taste buds, its primary high affinity receptor, trkB, was not
      prominently expressed in the neurons. The results are consistent with the
      interpretation that at least some, perhaps most, of the trophic influence on the
      sensory neurons is derived from the neuronal somata, and the trophic effect is
      paracrine or autocrine, rather than target derived. The BDNF in the taste bud may
      also act in a paracrine or autocrine manner on the trkB expressed in taste buds,
      as shown by others.

PMID- 15495214
TI  - The development of functional imaging in the diagnosis, management and
      understanding of childhood brain tumours.
AB  - Imaging plays a fundamental role in the management of children with brain
      tumours. A series of new techniques, commonly grouped under the heading
      functional imaging, promise to give information on the properties and biological
      characteristics of tissues thereby adding to the structural information available
      from current imaging. The EPSRC funded a workshop to bring together clinicians
      from the UK Children's Cancer Study Group and scientific experts in the field to
      identify clinical problems in childhood brain tumours that may be addressed by
      functional imaging and to develop a clinical test bed for applying, evaluating
      and developing this new technology. The presentations and discussion sessions
      from the workshop are summarised and a review of the current 'state of the art'
      for this rapidly developing area provided. A key output of the workshop was
      agreement on a series of hypotheses which can be tested in carefully designed
      clinical studies.

PMID- 15495215
TI  - Wiskott-Aldrich syndrome protein and the cytoskeletal dynamics of dendritic
      cells.
AB  - The regulated migration and spatial localization of dendritic cells in response
      to environmental signals are critical events during the initiation of
      physiological immune responses and maintenance of tolerance. Cells deficient in
      the Wiskott-Aldrich syndrome protein (WASP) have been used to demonstrate the
      importance of the dynamic remodelling of the actin-based cytoskeleton during the
      selective adhesion and migration of these cells. Unlike most cell types,
      macrophages, dendritic cells, and osteoclasts utilize a specialized adhesive
      array termed the podosome in order to migrate. Podosomes are composed of many of
      the same structural and regulatory proteins as seen in the more commonly found
      focal adhesion, but are unique in their requirement for WASP. Without WASP,
      podosomes cannot form and the affected cells are obliged to use focal adhesions
      for their migratory activities. Once activated by a series of upstream regulatory
      proteins, WASP acts as a scaffold for the binding of the potent actin nucleating
      protein complex known as Arp2/3. This article reviews the available evidence that
      suggests that failures in the regulation of the actin cytoskeleton may contribute
      significantly to the immunopathology of the Wiskott-Aldrich syndrome.

PMID- 15495216
TI  - Human alpha rhythms during visual delayed choice reaction time tasks: a
      magnetoencephalography study.
AB  - Magnetoencephalography (MEG) includes fast and comfortable recording procedures
      very suitable for the neurophysiological study of cognitive functions in aged
      people. In this exploratory MEG study in normal young adults, we tested whether
      very simple short-term memory (STM) demands induce visible changes in amplitude
      and latency of surface alpha rhythms. Two delayed response tasks were used. In
      the STM condition, a simple cue stimulus (one bit) was memorized along a brief
      delay period (3.5-5.5 s). In the control (no short-term memory; NSTM) condition,
      the cue stimulus remained available along the delay period. To make extremely
      simple the tasks, the explicit demand was visuospatial but the retention could be
      also based on phonological and somatomotor coding. Compared to the control
      condition, the amplitude of the alpha 1 (6-8 Hz) ERD decreased in the left
      hemisphere, whereas the amplitude of the alpha 2 (8-10 Hz) and alpha 3 (10-12 Hz)
      event-related desynchronization (ERD) increased in right and left parietal areas,
      respectively. Furthermore, the latency of the alpha ERD peak was slightly but
      significantly (P < 0.05) later in STM compared to control condition. In
      conclusion, whole-head MEG technology and very simple STM demands revealed
      significant changes of human neuromagnetic alpha rhythms in normal young adults.

PMID- 15495217
TI  - Noradrenaline up-regulates the neuronal and the inducible nitric oxide synthase
      isoforms in magnocellular neurons of rat brain slices.
AB  - Nitric oxide (NO) and noradrenaline (NA) are suggested to be implicated in the
      regulation of neuropeptide secretion in the supraoptic nuclei (SON) and the
      paraventricular nuclei (PVN) of the hypothalamus. Our study demonstrates short
      term interactions between NA and the activity and expression of NO synthase (NOS)
      in magnocellular neurons, by using an ex vivo model of hypothalamic slices. In
      the SON as well as in the PVN, total NOS activity exhibited a time-dependant
      increase after an incubation with NA. In the SON, this increase of total NOS
      activity was in part the consequence of stimulation of the iNOS activity.
      Coimmunodetections showed that cells expressing the inducible form of NOS were
      not astrocytes but magnocellular neurons. Steady-state levels of iNOS and nNOS
      mRNA were dramatically enhanced by NA, particularly in the SON. Consequently, we
      provide new evidence that iNOS could play an important role in multiple
      physiological functions, including extracellular fluid balance, lactation, and
      parturition.

PMID- 15495218
TI  - Keratins and skin disorders.
AB  - The association of keratin mutations with genetic skin fragility disorders is now
      one of the best-established examples of cytoskeleton disorders. It has served as
      a paradigm for many other diseases and has been highly informative for the study
      of intermediate filaments and their associated components, in helping to
      understand the functions of this large family of structural proteins. The keratin
      diseases have shown unequivocally that, at least in the case of the epidermal
      keratins, a major function of intermediate filaments is to provide physical
      resilience for epithelial cells. This review article reflects on the variety of
      phenotypes arising from mutations in keratins and the reasons for this variation.

PMID- 15495220
TI  - Siegfried Medal awarded to Joel m. Hawkins / Arndt Simon receives Liebig Medal /
      Lutz F. Tietze is awarded the Emil Fischer Medal.

PMID- 15495221
TI  - Syntheses of tetrodotoxin.

PMID- 15495222
TI  - Surface-templated nanostructured films with two-dimensional ordered arrays of
      voids.

PMID- 15495225
TI  - Testosterone, aging, and body composition in men from Harare, Zimbabwe.
AB  - To examine age-related changes in body composition and testosterone (T) among men
      in an urban sub-Saharan African population, measures of body composition and
      salivary T were obtained from 109 males ages 20-78 in Harare, Zimbabwe. Measures
      included height, weight, suprailiac and triceps skinfold, and percent body fat by
      bioelectric impedance (BIA). Saliva samples were assayed for T using
      radioimmunoassay. Average BMI of the overall sample (23.16 (SD = 18.12) kg/m(2)
      was close to Western populations, while salivary T levels (AM = 196 +/- 96
      pmol/l; pm = 172 +/- 98 pmol/l) were much lower. Both morning (beta = -0.535; P <
      0.001) and afternoon salivary T declined with age (beta = -0.385; P < 0.001).
      Multiple regression models indicate that pm salivary T (beta = 0.24; P = 0.025),
      was a predictor of fat-free mass, but neither am nor pm salivary T was related to
      fat mass or other measures of body composition. In addition, height was
      significantly related to pm salivary T levels in men under the age of 60.
      Multivariate regression indicates that pm salivary T is a predictor of fat-free
      mass when controlled for height and adiposity. These findings suggest that T is
      related to both lean mass and overall body size among men from a non-Western
      nonsubsistence population. As such they are consistent with the hypothesis that
      bioavailable T plays a role in energetic allocation among human males.

PMID- 15495226
TI  - Pathological situations characterized by altered actin isoform expression.
AB  - Modulation of actin isoform expression is a well-established feature of
      developmental phenomena. As one might expect, it is also characteristic of
      several pathological situations that are the subject of the present review. alpha
      Smooth muscle actin has proven to be a reliable marker for identifying (a)
      vascular smooth muscle cells during vascular development and vascular diseases,
      and (b) myofibroblasts during wound healing, fibrocontractive diseases, and
      stromal reaction to epithelial tumours. The hallmark of a differentiated
      myofibroblast relies on the acquisition of an organized contractile apparatus
      characterized by alpha-smooth muscle actin-expressing stress fibres. More and
      more data suggest that alpha-smooth muscle actin plays a direct role in
      myofibroblast contractile activity through its N-terminal domain AcEEED. Newly
      developed antibodies against alpha-skeletal and alpha-cardiac actins have allowed
      the detection of subpopulations of alpha-skeletal positive cardiomyocytes in
      adult, hypertrophic, and failing heart. These antibodies have also permitted us
      to identify the differentiation degree of malignant cells in tumours such as
      rhabdomyosarcoma. Whether the differential expression of actin isoforms in human
      diseases is functionally relevant is not yet fully established, although studies
      on human actin mutations, actin null mice, and the N-terminal end of alpha-smooth
      muscle actin support this possibility.

PMID- 15495227
TI  - Stability of variables associated with the metabolic syndrome from adolescence to
      adulthood: the Aerobics Center Longitudinal Study.
AB  - The purpose of the study was to examine the stability of variables associated
      with the metabolic syndrome from adolescence to adulthood. The sample included 48
      subjects from the Aerobics Center Longitudinal Study who had one clinical visit
      during adolescence (mean age = 15.8 years) and a follow-up visit during adulthood
      (mean age = 26.6 years). The following variables were considered: treadmill time
      to exhaustion (TM), body mass index (BMI), waist circumference (WC), percent body
      fat (%BF), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C),
      TC:HDL-C, triglycerides (TG), glucose (GLU), and systolic (SBP), diastolic (DBP),
      and mean (MAP) blood pressure. A composite risk factor score using variables
      consistent with the WHO and ATP III definition of the metabolic syndrome (WC, HDL
      C, TG, MAP, and GLU) was calculated. Tracking coefficients were computed as
      partial correlations, controlling for length of follow-up (mean = 11 years).
      Tracking coefficients (r values) were moderate for all variables (TM, 0.53; BMI,
      0.64; WC; 0.79;%BF, 0.44; TC, 0.62; HDL-C, 0.60; TG, 0.54; TC:HDL-C, 0.78; SBP,
      0.45; and MAP, 0.41), except GLU (0.26) and DBP (0.21). The composite risk factor
      score also tracked moderately well (0.56) from adolescence into adulthood. The
      results support previous findings that variables associated with the metabolic
      syndrome track moderately well from adolescence to adulthood. The findings
      support the prevention and treatment of obesity, atherosclerosis, type 2
      diabetes, and the metabolic syndrome during childhood and adolescence.

PMID- 15495229
TI  - Prevalence of overweight and obesity in 7-9-year-old Portuguese children: trends
      in body mass index from 1970-2002.
AB  - The aim of this study was to assess the prevalence of overweight and obesity in
      Portuguese children age 7-9 years and to analyze trends in body mass index (BMI)
      from 1970-2002. Data were collected from October 2002 to June 2003 in a random
      sample of Portuguese children. Height and weight were measured and BMI (Kg/m(2))
      was calculated. The International Obesity TaskForce (IOTF) cutoffs to define
      overweight and obesity were used. In the total sample we found 20.3% of
      overweight children and 11.3% of obese children. These results indicate a
      prevalence of overweight/obesity of 31.5%. Girls presented higher percentages of
      overweight than boys except at age 7.5. Girls also showed a higher percentages of
      obesity than boys except at age 9. From 1970 to 1992 and 1992 to 2002, height,
      weight, and BMI increased at different velocities: weight increased faster than
      height, and, consequently, BMI increased more in the last period than in the
      first one, leading to an increase in obesity values. Compared to published data
      by IOTF on other European countries, who applied the same methods to define
      overweight and obesity, Portuguese children showed the second-highest mean values
      in overweight/obesity. Italy showed the highest values (36%). The present study
      shows a very high prevalence of overweight/obesity (31.5%) in Portuguese children
      compared to other European countries. Portugal followed the trend of other
      Mediterranean countries like Spain (30%), Greece (31%), and Italy (36%). These
      high values require a national intervention program to control childhood obesity.

PMID- 15495228
TI  - Validation of different bioimpedance analyzers for predicting cell mass against
      whole-body counting of potassium (40K) as a reference method.
AB  - This study compared two different tetrapolar bioimpedance (BIA) devices for
      estimating body cell mass (BCM), validated them against whole-body counting of
      (40)K (TBK method), and developed improved prediction equations for estimating
      BCM from BIA. In 50 healthy volunteers (age 23-65 years, BMI 18.6-27.7 kg/m(2)),
      BCM was estimated with the BIA devices Nutriguard-M (Data Input, Germany) and
      Soft-Tissue-Analyzer-STA (Akern, Italy) and by the TBK method. Methods were
      compared by the Bland-Altman procedure. New prediction equations for BCM were
      developed by multiple stepwise regression analysis based on a single BIA parallel
      model. The Akern device gives similar mean estimates of BCM compared to the Data
      Input device in males (33.5 vs. 33.3 kg, P = 0.789), but higher values in females
      (24.6 vs. 22.8 kg; P < 0.001). Both BIA devices overestimate mean BCM relative to
      the TBK method; in males by 5.0 kg (Data Input, P < 0.001) and 5.1 kg (Akern, P <
      0.001); in females by 2.3 kg (Data Input, P < 0.001) and 4.1 kg (Akern, P <
      0.001). Limits of agreement between BIA and TBK methods are for males +/-4.99 kg
      (Data Input) and +/-7.16 kg (Akern); for females, +/-4.69 kg (Data Input) and +/
      4.12 kg (Akern). New equations were developed for estimating BCM for both BIA
      analyzers (Data Input, R(2) = 0.91, SEE = 1.46 kg; Akern, R(2) = 0.90, SEE = 1.48
      kg). Since estimates of BCM by the present BIA devices do not differ in males,
      they might be interchangeable. This does not hold true for females. Because both
      BIA devices overestimate BCM, the newly developed device-specific equations which
      reduce bias and limits of agreement should be applied.

PMID- 15495230
TI  - Exploring northeast African metric craniofacial variation at the individual
      level: a comparative study using principal components analysis.
AB  - A principal components analysis was carried out on male crania from the northeast
      quadrant of Africa and selected European and other African series. Individuals,
      not predefined groups, were the units of study, while nevertheless keeping group
      membership in evidence. The first principal component seems to largely capture
      "size" variation in crania from all of the regions. The same general morphometric
      trends were found to exist within the African and European crania, although there
      was some broad separation along a cline. Anatomically, the second principal
      component captures predominant trends denoting a broader to narrower nasal
      aperture combined with a similar shape change in the maxilla, an inverse relation
      between face-base lengths ("projection") and base breadths, and a decrease in
      anterior base length relative to base breadth. The third principal component
      broadly describes trends within Africa and Europe: specifically, a change from a
      combination of a relatively narrower face and longer vault, to one of a wider
      face and shorter vault; it shows the northeast quadrant Africans along a cline
      with the other Africans. Stated in relative terms, the northeastern Africans tend
      to exhibit narrower bases in relationship to more projecting faces, and broader
      nasal areas than Europeans, although there is range of variation. Relative to the
      other African groups, they have narrower nasal areas and narrower faces in
      relationship to vault length. The crania from the northeast quadrant of Africa
      collectively demonstrate the greatest pattern of overlap with both Europeans and
      other Africans. Variation was found to be high in all series but greatest in the
      African material as a whole. Individuals from different geographical regions
      frequently plotted near each other, revealing aspects of variation at the level
      of individuals that is obscured by concentrating on the most distinctive facial
      traits once used to construct "types." The high level of African interindividual
      variation in craniometric pattern is reminiscent of the great level of molecular
      diversity found in Africa. These results, coupled with those of Y chromosome
      studies, may help generate hypotheses concerning the length of time over which
      recent craniometric variation emerged in Africa.

PMID- 15495231
TI  - Variation in longitudinal diaphyseal long bone growth in children three to ten
      years of age.
AB  - Data from the Child Research Council (Denver, CO) were analyzed to model
      longitudinal growth changes in the humerus, radius, femur, and tibia in 31 boys
      and 36 girls between 3 and 10 years of age. Multilevel modeling of growth changes
      allowed efficient estimates of bone size and bone growth variation to be obtained
      as well as comparisons of growth patterns within and between limbs. The long
      bones displayed decelerating growth through time, with greater velocities for the
      larger lower limb (vs. smaller upper limb) bones and the larger proximal (vs.
      smaller distal) elements within limbs. Coordination for bone size and growth
      velocity is good both within and between limbs, suggesting a common growth
      control mechanism that should make growth prediction possible. Adjusted for size,
      the tibia appears to be the most variable of these four long bones, which may be
      due to a combination of environmental effects and flexible growth potential.

PMID- 15495232
TI  - Catch-up reproductive maturation in rural Tonga girls, Zambia?
AB  - To compare the timing of reproductive maturation among urban and rural Tonga
      girls in Zambia, anthropometric measures and Tanner stages of breast development
      were obtained. Subjects were 774 (282 rural, 492 urban) girls ages 6-18. Results
      indicate that rural girls are shorter and have smaller triceps and subscapular
      skinfolds than their urban counterparts. Median age at menarche for the entire
      sample, as estimated by probit analysis, was 14.8 years (95% CL = 14.34-15.40).
      Onset of breast development among urban girls was significantly younger than for
      the rural girls: 11.47 (95% CL 11.22-11.71) years vs. 13.15 (95% CL 12.40-14.15)
      years. In contrast, the two groups did not differ in timing of pubertal
      completion as assessed by median age for Tanner Breast Stage 5: 17.01 (95% CL
      16.30-18.33) vs. 16.96 (95% CL 16.37-17.56) years. Predictors of pubertal onset,
      based on multivariate logistic regression, included dental maturation, height,
      and triceps skinfold. Triceps skinfold was the only significant predictor of
      pubertal completion. These results suggest that rural girls progress through
      puberty more rapidly than the urban girls despite their later start. This finding
      of maturational catch-up contrasts with earlier urban/rural comparisons of girls
      as well as previous results among Gwembe boys, for which later pubertal onset is
      associated with longer duration of pubertal maturation. While the mechanism
      remains unclear, biocultural explanations suggest preferential feeding during
      adolescence as a source for rural girl's maturational catch-up.

PMID- 15495233
TI  - Morphological variation and airflow dynamics in the human nose.
AB  - Airflow dynamics are recognized as being important to the functioning of the
      human nose in conditioning and filtering inspired air, yet these dynamics are
      poorly understood. Despite considerable research on airflow dynamics by
      otolaryngologists, respiratory physiologists, and toxicologists, major
      disagreements remain about the nature of airflow in the human nose. Specifically,
      there is little consensus about the character of nasal airflow regimes (laminar
      or turbulent) and about the major pathways of airflow through the internal
      chamber. Additionally, a number of features in the human nose have been argued to
      enhance airflow turbulence, thus increasing the exposure of moving air to the
      nasal mucosa and facilitating heat and moisture exchange in cold and/or dry
      climates. These features include: an inferior orientation of the nares; a nasal
      sill that is high relative to the floor of the internal nasal chamber; a nasal
      valve that is small in cross-sectional area relative to that of the internal
      chamber; and large, projecting conchae. The claim that these features affect
      airflow dynamics has never been tested. To clarify the nature of human nasal
      airflow and to test these claims of functional significance to nasal variation,
      we studied airflow across physiological flow rates using water and dye flowing
      through anatomically accurate acrylic models of human nasal air passageways (with
      adjustment of water flow rates to maintain dynamic similarity). The models were
      derived from direct casting of the nasal passageways of 10 Caucasian
      ("leptorrhine") cadavers (six male, four female). Measures of naris angle, nasal
      sill height, nasal valve area relative to internal chamber cross-sectional area,
      and relative projection of the inferior and middle turbinates were taken directly
      on the resulting casts. The relationships between aspects of nasal morphology and
      turbulent air flow were evaluated by examining the flow regimes (laminar,
      semiturbulent, or turbulent) at varying flow rates, with the expectation that the
      greater the development of the proposed turbulence-enhancing features the slower
      the flow rate at which flow would shift from one regime to another. Flow
      characteristics (both flow regimes and principal pathways) were highly variable
      within our sample. The relative projection of the inferior turbinate was the only
      variable that significantly affected the flow rate at which flow became
      turbulent. However, more projecting turbinates appear to laminate flow rather
      than to induce turbulence. Nostril orientation was moderately correlated with
      flow dynamics (with more inferiorly directed nares producing turbulence at slower
      flow rates), but this correlation was not statistically significant. Relative
      nasal valve area and nasal sill height were unrelated to turbulence in our
      models.

PMID- 15495234
TI  - Behavioral and physiological indices related to BMI in a cohort of primary
      schoolchildren in Greece.
AB  - The purpose of this study was to investigate the differences between normal
      weight and overweight primary schoolchildren in terms of certain cardiovascular
      disease (CVD) risk factors and furthermore to identify behavioral correlates
      significantly affecting their body mass index (BMI). The sample consisted of 198
      children with a mean age of 11.5 +/- 0.4 years (106 females and 92 males). Data
      was obtained on children anthropometry, plasma lipids, plasma glucose, dietary
      intake, cardiorespiratory fitness, and physical activity. Significant gender
      differences were observed for most of these parameters, with boys being more
      active and fit but also spending more time on sedentary activities and exhibiting
      higher intake of energy and fat compared to girls. Using the International
      Obesity Task Force's (IOTF) BMI cut-off points, the prevalence of overweight and
      obesity was estimated to be 35.6% and 6.7% among boys and 25.7% and 6.7% among
      girls, respectively. Overweight and obese children had higher levels of plasma
      triglycerides (TG) and total cholesterol to HDL-cholesterol (TC/HDL-C) ratio and
      lower levels of HDL-C and physical fitness compared to their normal-weight peers.
      Among the behavioral variables tested, only participation in organized sports,
      cardiorespiratory fitness, and TV watching were significantly correlated with
      BMI, while energy and fat intake were found to have no significant effect. The
      current study suggests that even in childhood, overweight and obesity are
      indicative of an unfavorable lipidemic profile. Among the behavioral parameters
      known to affect BMI, those found to exert a significant effect were organized
      physical activities, cardiorespiratory fitness, and TV watching, but not energy
      or fat intake.

PMID- 15495235
TI  - Desminopathies in muscle disease.
AB  - A recently identified class of myopathies is produced by abnormal desmin, and is
      characterized by a disorganization of the desmin filament network, the
      accumulation of insoluble desmin-containing aggregates, and destructive changes
      in the sarcomeric organization of striated muscles. The desmin filaments interact
      with various other cytoskeletal proteins. The distinct clinical phenotypes are
      heterogeneous, with progressive skeletal myopathy, cardiomyopathy, and
      respiratory insufficiency as the most prominent features. Most of the desmin
      mutations are autosomal dominant. Identification of the causal genetic mutations
      shows that the desmin gene is not the only gene implicated in desminopathies;
      other genes encoding desmin-associated proteins, such as alpha-B-crystallin, and
      synemin may also be involved. Patients with mutations in their alpha-B-crystallin
      gene, which produce similar skeletal and cardiac myopathies, also have opaque
      lenses. Knockout mice have helped to reveal the fundamental role of desmin
      filaments in cell architecture, sarcomere alignment, myofibril organization, and
      the distribution of mitochondria. Transgenic mice, which accumulate aggregates of
      desmin and associated proteins in their muscles, show that the loss of desmin
      intermediate function as a result of mutations in desmin itself, or in the desmin
      associated constituents, is important for disease progression.

PMID- 15495237
TI  - Intractable hiccups may develop with cyclophosphamide infusion.

PMID- 15495238
TI  - Proportion of drug-related serious rare blood dyscrasias: estimates from the
      Berlin Case-Control Surveillance Study.
AB  - Drugs are an important cause of serious rare blood dyscrasias. To estimate the
      proportion of drug-related cases, we used data from the ongoing Berlin Case
      Control Surveillance Study. The analysis included a total of 171 cases. The
      number of cases in which a drug etiology was assessed as at least "possible" was
      n = 29 (97%) for acute agranulocytosis, n = 4 (0.21%) for aplastic anemia, n = 8
      (26%) for immune hemolytic anemia, n = 20 (25%) for immune thrombocytopenia, and
      n = 2 (20%) for thrombotic thrombocytopenic purpura/hemolytic uremic syndrome.
      Our analysis suggests that a substantial fraction of blood dyscrasias may be
      attributable to drug therapy.

PMID- 15495239
TI  - Doxycycline, gastrointestinal bleeding, and thrombotic microangiopathy.

PMID- 15495241
TI  - 5-Azacytidine supports the long-term repopulating activity of cord blood CD34(+)
      cells.
AB  - DNA methylation plays important roles in a wide range of biological phenomena,
      especially in the embryonic development and tumorigenesis. However, correlations
      between differentiation and DNA methylation have not been clarified well in each
      differentiation system. In this study, we focused our attention on regulatory
      roles of DNA methylation in normal hematopoietic differentiation using a
      demethylating reagent, 5-azacytidine (5-AzaC). As a source of hematopoietic
      progenitor cells, we used CD34(+) cells prepared from human umbilical cord blood
      and examined the effects of 5-AzaC on the colony-forming activity and the long
      term culture-initiating (LTC-IC) activity of these cells. 5-AzaC treatment
      increased LTC-IC frequency 1.57- to 2.50-fold as compared to the nontreated
      control. In parallel to this, immunoblotting analysis showed that the intensity
      of overall DNA methylation decreased after 5-AzaC treatment. These results
      indicated the involvement of DNA methylation and demethylation in controlling
      immaturity of hematopoietic progenitor cells and the usefulness of 5-AzaC for
      regulating this immaturity.

PMID- 15495242
TI  - Rituximab for refractory Evans syndrome and other immune-mediated hematologic
      diseases.
AB  - The authors describe a 21-year-old man with long-lasting Evans syndrome
      refractory to corticosteroids and immunosuppressive agents; the patient responded
      to four weekly infusions of rituximab. The patient relapsed with thrombocytopenia
      7 months post-therapy and was successfully re-treated with two weekly doses of
      the same monoclonal antibody. He remains in remission for 7-plus months after the
      second treatment. Therapy was well tolerated, and no infectious complications
      occurred, despite avoiding administration of prophylactic gammaglobulin.
      Rituximab appears safe and modestly effective in a variety of immune-mediated
      hematologic diseases, including autoimmune hemolytic anemia, chronic immune
      thrombocytopenia, Evans syndrome, pure red cell aplasia, mixed type II
      cryoglobulinemia, cold agglutinin disease, and Waldenstrom's macroglobulinemia.
      However, as most of the published literature consists of case reports and small
      case series, international collaboration is essential in order to better define
      the efficacy and safety of this agent in children and adults with hematologic
      diseases.

PMID- 15495240
TI  - The cytoskeleton in neurodegenerative diseases.
AB  - Abundant abnormal aggregates of cytoskeletal proteins are neuropathological
      signatures of many neurodegenerative diseases that are broadly classified by
      filamentous aggregates of neuronal intermediate filament (IF) proteins, or by
      inclusions containing the microtubule-associated protein (MAP) tau. The discovery
      of mutations in neuronal IF and tau genes firmly establishes the importance of
      neuronal IF proteins and tau in the pathogenesis of neurodegenerative diseases.
      Multiple IF gene mutations are pathogenic for Charcot-Marie-Tooth (CMT) disease
      and amyotrophic lateral sclerosis (ALS)--in addition to those in the copper/zinc
      superoxide dismutase-1 (SOD1) gene. Tau gene mutations are pathogenic for
      frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), and
      tau polymorphisms are genetic risk factors for sporadic progressive supranuclear
      palsy (PSP) and corticobasal degeneration (CBD). Thus, IF and tau abnormalities
      are linked directly to the aetiology and pathogenesis of neurodegenerative
      diseases. In vitro and transgenic animal models are being used to demonstrate
      that different mutations impair protein function, promote tau fibrilization, or
      perturb tau gene splicing, leading to aberrant and distinct tau aggregates. For
      recognition of these disorders at neuropathological examination,
      immunohistochemistry is needed, and this may be combined with biochemistry and
      molecular genetics to properly determine the nosology of a particular case. As
      reviewed here, the identification of molecular genetic defects and biochemical
      alterations in cytoskeletal proteins of human neurodegenerative diseases has
      facilitated experimental studies and will promote the development of assays of
      molecules which inhibit abnormal neuronal IF and tau protein inclusions.

PMID- 15495243
TI  - Megakaryocyte-like giant myeloma cells.

PMID- 15495244
TI  - Lymphoma-associated paraneoplastic angioedema with normal C1-inhibitor activity:
      does danazol work?
AB  - A patient with splenic marginal zone lymphoma presented with severe, symptomatic
      acquired angioedema. Unlike previously reported cases, his serum levels of
      complement and C1 inhibitor (C1-INH) were not decreased. Nonetheless, he
      responded clinically to treatment with an attenuated androgen and, after
      therapeutic splenectomy, has been maintained asymptomatic without androgen
      therapy for 5 years. Thus stimulation of C1-INH synthesis may overcome
      paraneoplastic angioedema in patients with lymphoproliferative disorders despite
      the absence of typical evidence for a quantitative or qualitative defect in C1
      INH. Androgens should not be withheld despite a normal level of C1-INH and
      complement in symptomatic patients.

PMID- 15495245
TI  - Rapid irreversible encephalopathy associated with anti-D immune globulin
      treatment for idiopathic thrombocytopenic purpura.
AB  - Intravenous Rho (D) immune globulin (IV RhIG, WinRho SDF) has been shown to be a
      safe treatment for idiopathic thrombocytopenic purpura (ITP). Common side effects
      of IV RhIG include mild hemolysis, febrile reaction, and headache. Significant
      hemolysis with renal impairment following IV RhIG has been reported. We report a
      case of irreversible encephalopathy 48 hr following an infusion of IV RhIG for
      treatment of ITP.

PMID- 15495246
TI  - Acute promyelocytic leukemia and HIV-1 infection: case report and review of the
      literature.
AB  - We report a 27-year-old man with HIV-1 infection who developed acute
      promyelocytic leukemia (APL) with a novel complex three-way chromosomal
      translocation t(15;16;17). Induction of remission and consolidation with all
      trans-retinoic acid (ATRA)- and anthracycline-based chemotherapy was followed by
      maintenance therapy consisting of ATRA, 6-mercaptopurine (6-MP), and methotrexate
      (MTX). Highly active antiretroviral therapy (HAART) was continued with brief
      interruptions. He remains in complete remission 40 months after diagnosis.

PMID- 15495247
TI  - HIV and plasmablastic lymphoma manifesting in sinus, testicles, and bones: a
      further expansion of the disease spectrum.
AB  - Patients with HIV infection are at increased risk for B-cell neoplasms and plasma
      cell dyscrasias. Both B cell and plasma cell tumors tend to be intermediate or
      high grade and are frequently associated with Epstein-Barr virus. Patients with
      HIV infection are also at higher risk of acquiring plasmablastic lymphoma. Until
      this time, only sinus, oral gastrointestinal, and lung manifestation have been
      noted. In this report we describe a 41-year-old male with HIV infection who
      developed multiple pleomorphic, extramedullary plasmablastic lymphomas associated
      with Epstein-Barr virus. We review the clinical and immunological features of his
      malignancy and thereby expand the spectrum of disease to include additional sites
      (bones, testicles) not previously reported.

PMID- 15495248
TI  - Pneumococcemia as the presenting feature of multiple myeloma.
AB  - Multiple myeloma is associated with a susceptibility to bacterial infections,
      specifically for encapsulated organisms such as Streptococcus pneumoniae.
      However, severe bacterial infection as the initial presentation of this disease
      has been rarely reported. The most common presenting features are anemia, lytic
      lesions, hypercalcemia, and renal failure. We report two cases of pneumococcal
      bacteremia as the initial manifestation of an underlying multiple myeloma. The
      first case is of a 68-year-old woman with pneumococcal pneumonia and bacteremia,
      presenting with a white blood cell count of 900/microL and mild anemia. Further
      work-up disclosed monoclonal IgG kappa and 50% plasma cells in bone marrow. Her
      course was complicated by acute renal failure requiring hemodialysis. The second
      patient is a 57-year-old man presenting with acute pneumococcal meningitis and
      bacteremia. Due to prior bacterial epiglottitis, further work-up disclosed IgG
      lambda monoclonal spike and 40% plasma cells in bone marrow. Both cases responded
      to antibiotic therapy without complications. These two cases add to the few
      patients described in the literature with pneumococcemia as the first sign of
      multiple myeloma. Features that were common in most of these cases, and that
      should lead to a suspicion of myeloma in an otherwise asymptomatic patient, are
      S. pneumoniae bacteremia, leukopenia, mild anemia, history of prior bacterial
      infections, and indirect evidence of a paraproteinemia, such as increased total
      protein levels with low albumin.

PMID- 15495249
TI  - Streptococcus bovis septic shock due to contaminated transfused platelets.
AB  - Although most physicians and the public are primarily concerned about the risk of
      transmitting human immunodeficiency virus (HIV) or hepatitis virus during a
      platelet transfusion, bacterial contamination is actually the most common
      infectious complication. Unlike red blood cells, platelets are stored at room
      temperature (20-24 degrees C), which raises the risk of bacterial proliferation.
      The risk of bacterial sepsis is 2.5-fold higher for each unit of transfused
      platelets compared to each unit of red blood cells. We report an unusual case of
      Streptococcus bovis septic shock associated with a contaminated platelet
      transfusion.

PMID- 15495250
TI  - The keratin cytoskeleton in liver diseases.
AB  - The keratin intermediate filament (IF) cytoskeleton of hepatocytes has
      continuously gained medical relevance over the last two decades. Originally it
      was mainly recognized as a differentiation marker for diagnostic purposes in
      pathology. However, keratin IFs were soon identified as major cellular structures
      to be affected in a variety of chronic liver diseases, such as alcoholic and non
      alcoholic steatohepatitis (ASH, NASH), copper toxicosis, and cholestasis. Based
      on observations in keratin gene knock-out mice, the insight into the functional
      role of keratins was extended from a mere structural role providing mechanical
      stability to hepatocytes, to an additional role as target and modulator of toxic
      stress and apoptosis. The functional relevance of keratins in human diseases has
      recently been underlined by the identification of mutations in keratin genes in
      patients with liver cirrhosis.

PMID- 15495251
TI  - Characterization of hemoglobin bassett (alpha94Asp-->Ala), a variant with very
      low oxygen affinity.
AB  - Hemoglobin (Hb) Bassett, an abnormal Hb variant with a markedly reduced oxygen
      affinity, was discovered in a Caucasian (Anglo-Saxon) male child who experienced
      episodes of cyanosis. Cation-exchange and reversed-phase (RP) high-performance
      liquid chromatography (HPLC) showed that the patient has an abnormal Hb, with a
      mutation in the alpha-globin. Tryptic peptide digest of the abnormal alpha-globin
      with subsequent HPLC analysis revealed abnormal elution of the alpha-T11 peptide.
      Further studies with Edman sequencing and electrospray mass spectrometry of
      tryptic peptide alpha-T11, as well as structural analysis by X-ray
      crystallography revealed an Asp-->Ala substitution at the alpha94 (G1) position,
      a match for Hb Bassett. Detailed functional studies showed that this Hb variant
      had a markedly reduced oxygen affinity (P(50) at pH 7.0 = 22 mmHg; Hb A P(50) =
      10.5 mmHg), reduced Bohr effect (-0.26 compared to - 0.54 in Hb A), and low
      subunit cooperativity (n = 1.4, compared to 2.6 in Hb A). X-ray crystallography
      results explain the probable effects of the structural modification on the oxygen
      binding properties of this Hb variant.

PMID- 15495252
TI  - Morbidity and mortality of deep sedation in outpatient bone marrow biopsy.
AB  - Deep sedation is being provided at an increasing rate for patients undergoing
      bone marrow biopsy and aspiration (BMBA). The aim of this study was to establish
      the safety of deep sedation used for adults undergoing BMBA. A nonrandomized
      database analysis and retrospective review of patient records from January 1997
      to December 2000 was performed; 5,811 patients were identified as having
      undergone their first outpatient BMBA. Outcome measures included 30-day mortality
      and same-day hospital admission; surrogate measures included need for a surgical
      procedure or receipt of red blood cells within the 48 hr following the BMBA.
      Patients who received intravenously administered midazolam, fentanyl, and
      propofol for maintenance of deep sedation plus infiltration of a local anesthetic
      (n = 2,604; 45%) comprised the deep sedation group; those who received
      infiltration of a local anesthetic but no intravenous sedation or analgesia (n =
      3,207; 55%) comprised the local anesthesia group. Patients in the deep sedation
      group compared to those in the local anesthesia group were less likely to die
      within 30 days (0.69% vs. 1.34%, P = 0.018) and less likely to receive red blood
      cells (1.27% vs. 2.25%, P = 0.006). No other differences between the groups were
      found. Although the study was retrospective and nonrandomized, the results
      suggest that the use of deep sedation for outpatient BMBA is as safe as using
      local anesthesia.

PMID- 15495253
TI  - Androgens and liver tumors: Fanconi's anemia and non-Fanconi's conditions.
AB  - The association between anabolic androgenic steroids and liver tumors was first
      noted in patients with Fanconi's anemia (FA). The hypotheses which led to this
      review were as follows: (1) androgen-treated individuals who do not have FA are
      also at risk of liver tumors; (2) parenteral as well as oral androgens may be
      responsible for liver tumors; (3) FA patients develop liver tumors after smaller
      and briefer androgen exposure than non-FA individuals; (4) the risk of hepatic
      neoplasms may depend on the specific androgen. Medline and Web of Science were
      searched for all cases of liver tumors associated with androgens. Information
      from individual cases was entered into a spreadsheet and descriptive statistical
      analyses were performed. Thirty-six FA cases and 97 non-FA cases with both
      nonhematologic disorders and acquired aplastic anemia (non-FA AA) were
      identified. The most common androgens were oxymetholone, methyltestosterone, and
      danazol. Hepatocellular carcinomas (HCC) were more often associated with
      oxymetholone and methyltestosterone, while adenomas were associated with danazol.
      Tumors were reported in six patients who received only parenteral and not oral
      androgens. FA patients were younger than non-FA patients when androgen use was
      initiated, and the FA patients developed tumors at younger ages. Non-AA patients
      were treated with androgens for longer periods of time, compared with FA and non
      FA AA patients. All patients on anabolic androgenic steroids are at risk of liver
      tumors, regardless of underlying diagnosis. The magnitude of the risk cannot be
      determined from currently available data, because the number of patients
      receiving androgens is unknown.

PMID- 15495254
TI  - Aberrant methylation of multiple tumor suppressor genes in acute myeloid
      leukemia.
AB  - Hypermethylator phenotype, a propensity of tumors to incur nonrandom concurrent
      methylation, has been described in several tumors, including acute myeloid
      leukemia (AML). More recent studies identified methylation of other tumor
      suppressor genes, DAP-kinase and SOCS1, singly in AML. We therefore assessed the
      methylation status of these genes concurrently with other known targets of
      methylation. We used methylation-specific PCR or COBRA to determine the extent of
      methylation of 10 genes in 28 AML samples from Turkey. In addition to DAP-kinase
      and SOCS1, we included ER, p15, and E-cadherin (reported to be frequently
      methylated) as well as p16, GSTP1, and HIC1 (reported as rarely methylated). We
      also included RARbeta and p73 for which only minimal data in AML is available.
      All samples were methylated at least in one locus and all except one demonstrated
      methylation of DAP-kinase, SOCS1, p15, and/or ER. DAP-kinase is the most
      frequently methylated gene in both pediatric (70%) and adult AML (55%). RARbeta
      is methylated in 18% and p73 in 10% of AMLs. Methylation of E-cadherin and
      RARbeta occurs preferentially in AMLs with high methylation index (MI), while
      epigenetic lesions in SOCS1, DAP-kinase, and p15 appear to be independent. MI may
      be age-dependent, with a peak in young adults. FAB M3 demonstrated a higher
      extent of methylation than M2/M4. This study provides an impetus for larger
      studies to define if the extent and pattern of methylation in subgroups of AML
      are clinically relevant.

PMID- 15495255
TI  - Autoimmune cytopenias associated with autoantibodies to nuclear envelope
      polypeptides.
AB  - A subset of anti-nuclear autoantibodies (ANA) are directed against nuclear
      envelope (NE) polypeptides and display by indirect immunofluorescence (IIF) a
      ring-like fluorescent pattern. We report herein 19 patients with autoimmune
      cytopenias associated with antibodies (Abs) to NE polypeptides. Anti-NE
      specificity was determined by immunoblot, using NE preparations and purified
      lamina fractions. Eleven sera reacted with lamin B(1), and two reacted with both
      lamin B(1) and an unidentified 150-kDa protein (p150). One serum reacted with
      only p150. Four sera reacted with lamins A and C, and one reacted with and an
      unidentified 52-kDa NE polypeptide (p52). Autoimmune cytopenias included
      hemolytic anemia (7 cases), thrombocytopenia (13 cases), and neutropenia (6
      cases). Five patients had 2 (3 cases) or 3 (2 cases) different cytopenias.
      Antiphospholipid antibodies (APLA) were detected in 14 patients, 2 of whom
      experienced thromboembolic events. A liver disorder was present in 7 patients.
      Systemic lupus erythematosus and lupus-like syndrome were diagnosed in 11 and 2
      patients, respectively. Cytopenias responded to steroids alone (13 patients), or
      together with intravenous immunoglobulins (2 patients), or cyclophosphamide (2
      patients). Two patients did not require treatment. Our results suggest that anti
      NE Abs need to be sought for in patients with peripheral cytopenias, particularly
      when they are associated with APLA and/or liver disorders. Their detection
      strongly suggests an autoimmune process. Such cytopenias are often manifestations
      of a lupus or lupus-like disease and are responsive to steroids.

PMID- 15495256
TI  - Immature granulocyte fraction in the peripheral blood is a practical indicator
      for mobilization of CD34(+) cells.
AB  - We propose a simple parameter that improves prediction of the number of CD34(+)
      cells in blood cells collected by apheresis for autologous peripheral blood stem
      cell (PBSC) transplantation following administration of granulocyte colony
      stimulating factor. The percentage of immature granulocytes including
      myeloblasts, promyelocytes, myelocytes, and metamyelocytes (LSI for left-shift
      index) immediately prior to the start of each apheresis correlated with the
      number of CD34(+) cells in PBSC collections (r = 0.79, P < 0.0001, Y = 0.227X -
      0.99, R(2) = 0.623) much better than did the white blood cell count (r = 0.07),
      currently the most commonly used predictor in deciding the initiation of
      apheresis. We then used receiver operating characteristic (ROC) curves to
      determine a cutoff point for LSI to prevent unnecessary apheresis. At LSI > 7.5,
      sensitivity and specificity of cutoff points in the probability of obtaining >1.0
      x 10(6) CD34(+) cells/kg BW were 93.3% and 94.3% (95% CI, 91.4-100.0%),
      respectively. When LSI reaches 15.25, nearly 100% of apheresis will attain the
      target CD34(+) cell dose. These findings indicate that LSI is a useful and simple
      method for predicting the yield of CD34(+) cells before the start of PBSC
      collection and avoiding unnecessary apheresis.

PMID- 15495257
TI  - Sickle cell crisis associated with hemophagocytic lymphohistiocytosis.
AB  - Sickle-beta(+) (beta(+)) thalassemia is a double heterozygous genetic disorder
      characterized by both a qualitative and quantitative abnormality. We present a
      case of an African American male who was first diagnosed with sickle cell disease
      (SCD) at the age 23 years when he presented with generalized bone pain, fever,
      and hepatosplenomegaly. Laboratory findings included thrombocytopenia, microcytic
      anemia, and markedly elevated ferritin. He was subsequently diagnosed with a
      sickle-beta thalassemia hemoglobinopathy. Findings in the bone marrow aspirate
      and biopsy were consistent with hemophagocytic lymphohistiocytosis (HLH). HLH
      resolved with the resolution of sickle cell bone pain crisis without use of
      immunosuppressive therapy. To the best of our knowledge this is the first
      documented case of HLH associated with sickle cell bone pain crisis.

PMID- 15495258
TI  - Management of patients with systemic mastocytosis: review of M. D. Anderson
      Cancer Center experience.
AB  - Mastocytosis is characterized by mast cell proliferation that may be limited to
      the skin (cutaneous mastocytosis) or may involve one or more extracutaneous
      organs, e.g., the bone marrow (systemic mastocytosis; SM). This study objective
      is to evaluate the features and outcome of patients referred to M. D. Anderson
      Cancer Center (MDACC) with SM. A search of the MDACC database from 1944 to 2002
      was conducted for patients with SM and review of their clinical charts. Eighteen
      patients with mastocytosis were identified in the MDACC database; 15 (11 males
      and 4 females) had SM and available information. Two had associated
      myelodysplastic syndrome (MDS), and one had acute myeloid leukemia (AML). The
      median age was 58 years (range 31-80). Nine patients were treated with
      subcutaneous interferon-alpha, and only 1 experienced temporary control of the
      disease. Three of these patients were then treated with imatinib mesylate:
      transient improvement was noted in two patients. One patient underwent stem cell
      transplantation as first therapy and achieved complete remission; this patient
      had associated MDS and is now in complete remission for 8 years. The patient with
      associated AML was treated with high-dose cytarabine and idarubicin; he has been
      in complete remission for 16 months. One patient was treated with induction
      chemotherapy consisting of high-dose cytarabine and 2CDA but expired due to
      sepsis. Three patients received symptomatic therapy only; these were the only 3
      patients who presented with normal blood counts. SM is rare and has no effective
      standard of care. Collaboration among academic centers to accrue enough patients
      to evaluate novel therapeutic strategies is needed.

PMID- 15495259
TI  - Serum ionized magnesium levels and ionized calcium-to-magnesium ratios in adult
      patients with sickle cell anemia.
AB  - Low levels of total magnesium in sickle cell erythrocytes have been linked to
      increased sickling due to cell dehydration. We tested the null hypothesis that
      adult sickle cell anemia (SCA) patients have the same serum level of ionized Mg
      (Mg(2+)) and Ca(2+)/Mg(2+) ratio as healthy African Americans (AA) and healthy
      Caucasians (CAUC). We measured serum Mg(2+) and ionized calcium (Ca(2+)) with ion
      selective electrodes and calculated the serum Ca(2+)/Mg(2+) ratios in patients
      with SCA and control groups (AA and CAUC). Seventy-four SCA patients and 61
      controls were compared. SCA patients had significantly (P < 0.001) lower levels
      of serum Mg(2+) (0.52 +/- 0.05) compared to healthy AA (0.57 +/- 0.04) and CAUC
      (0.62 +/- 0.03). Eighty-six percent of the adult SCA patients had serum Mg(2+)
      levels below the mean for the AA group, and 96% of SCA patients were above the AA
      group's mean serum Ca(2+)/Mg(2+). Of the SCA patients studied, 25.6% (95% CI,
      16.2-37.2%) had serum Mg(2+) levels below the racially adjusted lower limit of
      normal and 50% (95% CI, 38.1-61.9%) were above the upper limit of serum
      Ca(2+)/Mg(2+) for AA controls. By measuring serum Mg(2+) and Ca(2+), we were able
      to define a subset of SCA patients with hypomagnesemia and elevated Ca(2+)/Mg(2+)
      ratios, who may benefit from magnesium supplementation.

PMID- 15495260
TI  - Optimal docking area: a new method for predicting protein-protein interaction
      sites.
AB  - Understanding energetics and mechanism of protein-protein association remains one
      of the biggest theoretical problems in structural biology. It is assumed that
      desolvation must play an essential role during the association process, and
      indeed protein-protein interfaces in obligate complexes have been found to be
      highly hydrophobic. However, the identification of protein interaction sites from
      surface analysis of proteins involved in non-obligate protein-protein complexes
      is more challenging. Here we present Optimal Docking Area (ODA), a new fast and
      accurate method of analyzing a protein surface in search of areas with favorable
      energy change when buried upon protein-protein association. The method identifies
      continuous surface patches with optimal docking desolvation energy based on
      atomic solvation parameters adjusted for protein-protein docking. The procedure
      has been validated on the unbound structures of a total of 66 non-homologous
      proteins involved in non-obligate protein-protein hetero-complexes of known
      structure. Optimal docking areas with significant low-docking surface energy were
      found in around half of the proteins. The 'ODA hot spots' detected in X-ray
      unbound structures were correctly located in the known protein-protein binding
      sites in 80% of the cases. The role of these low-surface-energy areas during
      complex formation is discussed. Burial of these regions during protein-protein
      association may favor the complexed configurations with near-native interfaces
      but otherwise arbitrary orientations, thus driving the formation of an encounter
      complex. The patch prediction procedure is freely accessible at
      http://www.molsoft.com/oda and can be easily scaled up for predictions in
      structural proteomics.

PMID- 15495261
TI  - The cytoskeleton and disease.
AB  - Cytoskeletal research in recent years has revolutionized cell biology and
      biomedicine. The cytoskeleton spans the cytoplasm and interconnects the cell
      nucleus with the extracellular matrix, thereby forming a structural link between
      molecules involved in cell communication on the one hand, and gene expression on
      the other. Since the cytoskeleton is involved in virtually all cellular
      processes, abnormalities in this essential cellular component frequently result
      in disease. In this introduction, the basic structure of the cytoskeleton is
      briefly outlined. Furthermore, the disease processes in which the cytoskeleton
      plays a decisive role, and which are reviewed in detail in the papers in this
      issue, are briefly introduced. The advances in our understanding of the
      cytoskeleton and its function in disease will lead to new diagnostic and
      therapeutic applications in the foreseeable future.

PMID- 15495262
TI  - Laminopathies.
AB  - Nuclear lamins form a fibrous nucleoskeletal network of intermediate-sized
      filaments that underlies the inner nuclear membrane. It associates with this
      membrane through interactions with specific integral nuclear membrane proteins,
      while within this flattened lamin lattice the nuclear pore complexes are
      embedded. Next to this peripheral network, the lamins can form intranuclear
      structures. The lamins are the evolutionary progenitors of the cytoplasmic
      intermediate filament proteins and have profound influences on nuclear structure
      and function. These influences require that lamins have dynamic properties and
      dual identities as structural building blocks on the one hand, and transcription
      regulators on the other. Which of these identities underlies the laminopathies, a
      myriad of genetic diseases caused by mutations in lamins or lamin-associated
      proteins, is a topic of intense debate.

PMID- 15495263
TI  - Congenital myopathies: diseases of the actin cytoskeleton.
AB  - Congenital myopathies are clinical and genetic heterogeneous disorders
      characterized by skeletal muscle weakness ranging in severity. Three major forms
      have been identified: actin myopathy, intranuclear rod myopathy, and nemaline
      myopathy. Nemaline myopathy is the most common of these myopathies and is further
      subdivided into seven groups according to severity, progressiveness, and age of
      onset. At present, five genes have been linked to congenital myopathies. These
      include alpha-actin (ACTA1), alpha- and beta-tropomyosin (TPM3 and TPM2),
      troponin T (TNNT1), and nebulin (NEB). Their protein products are all components
      of the thin filament of the sarcomere. The mutations identified within these
      genes have varying impacts on protein structure and give rise to different forms
      of congenital myopathies. Greater understanding of muscle formation and cause of
      disease can be established through the study of the effect of mutations on the
      functional proteins. However, a major limitation in the understanding of
      congenital myopathies is the lack of correlation between the degree of sarcomeric
      disruption and disease severity. Consequently, great difficulty may be
      encountered when diagnosing patients and predicting the progression of the
      disorders. There are no existing cures for congenital myopathies, although
      improvements can be made to both the standard of living and the life expectancy
      of the patient through various therapies.

PMID- 15495264
TI  - The pathobiology of the septin gene family.
AB  - Septins are an evolutionarily conserved group of GTP-binding and filament-forming
      proteins that belong to the large superclass of P-loop GTPases. While originally
      discovered in yeast as cell division cycle mutants with cytokinesis defects, they
      are now known to have diverse cellular roles which include polarity
      determination, cytoskeletal reorganization, membrane dynamics, vesicle
      trafficking, and exocytosis. Septin proteins form homo- and hetero-oligomeric
      polymers which can assemble into higher-order filaments. They are also known to
      interact with components of the cytoskeleton, ie actin and tubulin. The precise
      role of GTP binding is not clear but a current model suggests that it is
      associated with conformational changes which alter binding to other proteins.
      There are at least 12 human septin genes, and although information on expression
      patterns is limited, most undergo complex alternative splicing with some degree
      of tissue specificity. Nevertheless, an increasing body of data implicates the
      septin family in the pathogenesis of diverse disease states including neoplasia,
      neurodegenerative conditions, and infections. Here the known biochemical
      properties of mammalian septins are reviewed in the light of the data from yeast
      and other model organisms. The data implicating septins in human disease are
      considered and a model linking these data is proposed. It is posited that septins
      can act as regulatable scaffolds where the stoichiometry of septin associations,
      modifications, GTP status, and the interactions with other proteins allow the
      regulation of key cellular processes including polarity determination.
      Derangements of such septin scaffolds thus explain the role of septins in disease
      states.

PMID- 15495265
TI  - Pathogen-induced actin filament rearrangement in infectious diseases.
AB  - Host defence mechanisms involve the establishment and maintenance of numerous
      barriers to infectious microbes, including skin and mucosal surfaces, connective
      tissues, and a sophisticated immune system to detect and destroy invaders.
      Defeating these defence mechanisms and breaching the cell membrane barrier is the
      ultimate challenge for most pathogens. By invading the host and, moreover, by
      penetrating into individual host cells, pathogens gain access to a protective
      niche, not only to avoid immune clearance, but also to replicate and to
      disseminate from cell to cell within the infected host. Many pathogens are
      accomplishing these challenges by exploiting the actin cytoskeleton in a highly
      sophisticated manner as a result of having evolved common as well as unique
      strategies.

PMID- 15495266
TI  - Cilia-related diseases.
AB  - There are at least eight categories of cilia in the human body and malfunctioning
      of any one or several of them will have different consequences for the patient. A
      genetic error of the respiratory cilia (9 + 2) is the cause of the airways
      disease named immotile-cilia syndrome (or PCD), whereas defective ependymal cilia
      (9 + 2) carries an increased risk of hydrocephalus. When the so-called nodal
      cilia (9 + 0) of the early embryo are malfunctioning, there is a random
      determination of asymmetry of the heart and visceral organs ('a 50% risk of situs
      inversus'). Some genes are responsible for the synthesis, transport, and assembly
      of the cilia, and mutations in these genes may lead to progressive degeneration
      of ciliary structures, such as the connecting cilium (9 + 0) of the photoreceptor
      cells-this is the cause of retinitis pigmentosa. Ciliary malfunctions due to
      genetic errors tend to be systemic and life-long, whereas acquired diseases are
      local and may be temporary only.

PMID- 15495267
TI  - Keratin mutations and intestinal pathology.
AB  - Whilst the importance of mutations in a wide range of keratins in skin fragility
      disorders is now well established, there is much less evidence for simple
      epithelial keratin involvement in disease. Some simple epithelial keratin
      mutations have been reported in liver cirrhosis and pancreatitis patients, and
      recently mutations in the simple epithelial keratin K8 were identified in a group
      of patients with inflammatory bowel disease (Crohn disease or ulcerative
      colitis). In comparison with the mutations seen in epidermal keratins, these
      simple epithelial mutations would be predicted to have mild consequences,
      although analysis shows that they do have a distinct effect. This review article
      discusses the evidence that these mutations are a predisposing factor for
      inflammatory bowel disease.

PMID- 15495268
TI  - Hereditary haemolytic anaemias: unexpected sequelae of mutations in the genes for
      erythroid membrane skeletal proteins.
AB  - Although the haemolytic anaemia may be the primary concern for hereditary
      spherocytosis and elliptocytosis patients, it is clear that their situation can
      be compromised by primary and secondary defects in erythroid and non-erythroid
      systems of the body. All seven of the red cell membrane skeletal proteins
      discussed in this review are also expressed in non-erythroid tissues, and
      mutations in their genes have the potential to cause non-erythroid defects. In
      some instances, such as the protein 4.1R and ANK1 neurological deficits, the
      diagnosis is clear. In other instances, because of the complex expression
      patterns involved, the non-erythroid effects may be difficult to assess. An
      example is the large multidomain, multifunctional band 3 protein. In this case,
      the location of the mutation can cause defects in one functional domain or
      isoform and not the other. In other cases, such as the beta-adducin null
      mutation, other isoforms may partially compensate for the primary deficiency. In
      such cases, it may be that the effects of the deficit are subtle but could
      increase under stress or with age. To be completely successful, treatment
      strategies must address both primary and secondary effects of the anaemia. If
      gene replacement therapy is to be used, the more that is known about the
      underlying genetic mechanisms producing the multiple isoforms the better we will
      be able to design the best replacement gene. The various animal models that are
      now available should be invaluable in this regard. They continue to contribute to
      our understanding of both the primary and the secondary effects and their
      treatment.

PMID- 15495269
TI  - Astrocyte intermediate filaments in CNS pathologies and regeneration.
AB  - Astroglial cells are the most abundant cells in the mammalian central nervous
      system (CNS), yet our knowledge about their function in health and disease has
      been limited. This review focuses on the recent work addressing the function of
      intermediate filaments in astroglial cells under severe mechanical or osmotic
      stress, in hypoxia, and in brain and spinal cord injury. Recent data show that
      when astrocyte intermediate filaments are genetically ablated in mice, reactive
      gliosis is attenuated and the course of several CNS pathologies is altered, while
      the signs of CNS regeneration become more prominent. GFAP is the principal
      astrocyte intermediate filament protein and dominant mutations in the GFAP gene
      have been shown to lead to Alexander disease, a fatal neurodegenerative condition
      in humans.

PMID- 15495270
TI  - Complexation of retroviruses with charged polymers enhances gene transfer by
      increasing the rate that viruses are delivered to cells.
AB  - BACKGROUND: We have previously found that retrovirus transduction is enhanced
      when an anionic polymer (chondroitin sulfate C) is added to virus stocks that
      contain an equal weight concentration of a cationic polymer (Polybrene). This
      observation was unexpected given that previous work has shown that cationic
      polymers enhance transduction while anionic polymers have the opposite effect.
      METHODS: Using model recombinant retroviruses and lentiviruses that encode for
      the Escherichia coli lacZ gene and quantitative assays of virus adsorption and
      transduction, we examined the mechanism of enhancement. RESULTS: We found that
      addition of oppositely charged polymers (Polybrene and chondroitin sulfate C) to
      virus stocks enhanced gene transfer by increasing the flux of active viruses to
      the cells. Virus-polymer complexes formed that did not reduce the stability of
      the viruses, yet were large enough to sediment, delivering the viruses to the
      cells more rapidly than by simple diffusion. The size of the complexes, the rate
      of sedimentation, and the levels of gene transfer increased with increasing
      concentrations of polymers. The degree to which transduction was enhanced ranged
      from 2- to nearly 40-fold, and varied depending on the type of cells and viruses
      used. Interestingly, we found that association of the viruses with the polymer
      complexes did not significantly hinder their ability to complete post-binding
      steps of transduction. CONCLUSIONS: Complexation of retroviruses with charged
      polymers significantly improves the efficiency of ex vivo gene transfer by
      increasing the number of active viruses that reach the cells.

PMID- 15495271
TI  - Identification of a naturally processed cyclin D1 T-helper epitope by a novel
      combination of HLA class II targeting and differential mass spectrometry.
AB  - T-helper (Th) cells play an important role in orchestrating the effector function
      of CTL in anti-tumor immunity. However, only a limited number of Th cell epitopes
      has been characterized. Here we describe a novel approach for identifying
      naturally processed and presented peptides derived from chosen antigens. This
      method combines a transfection step of antigen-presenting cells with a vector
      encoding a fusion protein between the Ii chain and the antigen of interest,
      elution of the HLA-bound peptides and identification of the antigen-derived
      peptides by mass spectrometric comparison to the non-transfected cells. In vitro
      stimulated Th cells against the identified peptide of interest specifically
      recognize transfectants overexpressing the cognate antigen. Using this approach,
      we were able to identify the HLA-DR4-restricted Th cell epitope NPPSMVAAGSVVAAV
      derived from cyclin D1, which is frequently overexpressed in tumors. This method
      will help in identifying peptide candidates for vaccination studies for tumor
      immunotherapy.

PMID- 15495272
TI  - Telemedicine in Baltic Sea region: experiences of Tartu University.

PMID- 15495273
TI  - Handball: the beauty or the beast.

PMID- 15495275
TI  - Education in family medicine--gains and dangers.
AB  - This editorial discusses the emerging evidence base for using family medicine as
      a core setting for medical training, and evaluates the challenges and impacts of
      this role on family medicine practice. Substantive, well designed educational
      opportunities can be effectively delivered in family medicine, and this has
      positive impacts on learning of clinical medicine, student attitudes towards
      patients, their understanding of population health, their choice of careers, and
      their respect for family medicine as a discipline. However, a poor standard of
      clinical practice and a lack of capacity in community based health care
      facilities could militate against such results being sustained and replicated in
      all countries. Medical schools in all parts of the world should be considering
      whether their family medical system can sustain a useful input to their
      curricula, and seeking to support colleagues in family medicine to develop their
      disciplinary base, because of the valuable contribution they can make to
      education as well as patient care and research.

PMID- 15495276
TI  - General practice east of Eden: an overview of general practice in Eastern Europe.
AB  - AIM: To review the status of family medicine in Eastern European countries,
      specifically the position of the discipline within the health care system, its
      academic status, and expected trends in the development of the discipline.
      METHODS: We used available data in the literature and information gathered from
      personal contacts with members of European Society of General Practice/Family
      Medicine (ESGP/FM) expert groups, European Academy of Teachers in General
      Practice (EURACT), and European General Practice Research Network (EGPRN).
      Personal interviews with key informants from countries that do not have members
      in these organizations were used. We also performed a Medline search using terms
      "primary health care" and "family medicine". RESULTS: It was difficult to get
      standardized information about the issues addressed. In some countries, contact
      persons and articles were impossible to find. Because of that, information from
      some countries is lacking (e.g. Belarus, Ukraine, the Kavkaz states and Central
      Asian republics). The information from the 14 countries showed that family
      medicine was formally widely recognized as a specific discipline. In 13 of them,
      there were some programs of vocational training. In 10 countries, academic
      recognition has resulted in rapid development in the past two decades, especially
      after 1989, but in Bulgaria and Moldova we found no evidence of family medicine
      departments. CONCLUSION: The position of general practice in most Central and
      Eastern European countries is formally adequate, but a lot of effort will still
      be needed to achieve the desired level of its recognition and quality.

PMID- 15495277
TI  - Family medicine in Croatia: past, present, and forthcoming challenges.
AB  - The aim of this paper is to present the effects of the reform of primary care by
      privatization and direct contracting between general practitioners/family
      physicians and the Croatian Institute for Health Insurance, as well as to propose
      possible improvements. Using the data of the Croatian Institute of Public Health,
      we analyzed the coverage of population and accessibility of service, management
      of chronic illnesses, home visits, and preventive check-ups in the family
      medicine service. In 2001, 2,408 (30.8% vocationally trained) doctors worked in
      the family medicine service, taking care of 3.759,248 (84.7%) registered
      inhabitants of Croatia. There was an average of 6 office encounters, 0.1 home
      visits, 0.05 preventive check-ups and 1.4 referrals per patient per year. Within
      the Project of Health System Reform a working group of primary care experts
      proposed the following improvements: 1) the family medicine service should be
      organized in accordance with the fundamental principles of accessibility,
      continuity, and integrated care; and 2) a multilayered financing model should be
      used, containing a capitation fee payment, fee for service payment, and specific
      program payment. Taking into account the European Union recommendation, a project
      aimed at ensuring the specialization of family medicine for all doctors working
      in the family medicine service was started in 2003. This study indicates that
      there is a gap between proclaimed health system improvements and effects of the
      reform of primary care. In order to achieve evidence-based health policy,
      concerted action of all participants in the decision-making process is needed.

PMID- 15495278
TI  - Are problems of academic medicine a new phenomenon?
AB  - Many of the problems of academic medicine are related to the actual challenges of
      health-care. Some disciplines have high prestige; these have advantages in
      education, while the needs of the society may differ to some extent. Introduction
      of the World Health Organization (WHO) concept on health as well as on
      functioning and disability into the training of physicians and more training in
      communication may remedy some of the discrepancies. The increase in the demand
      for physicians calls for improved ethical standards in the practice of importing
      health workers by the wealthy nations.

PMID- 15495279
TI  - Dilemma of an indigent country: Is academic medicine a good investment?
AB  - Academic medicine is a discipline which requires much financial expenditure and
      the profit is not always immediate. Therefore, an idea has been raised in some
      circles to limit the expenditures on it. The experience of Poland points out,
      however, that such a limitation will not bring benefit in the long run--just the
      opposite, it can bring about both social and economic loss. Even the countries
      that are not wealthy should invest in academic medicine, as this is a necessary
      condition for their harmonious growth.

PMID- 15495280
TI  - Academic medicine in a southern African country of Malawi.
AB  - Academic medicine is usually considered to be a tripartite composition of
      teaching, research, and health care services delivery or patient care. The
      meaning of each component varies with interpretation. Developing countries such
      as Malawi face particular challenges in the field of academic medicine, including
      research resources, financing, and the brain drain of health human resources.
      Such constraints contribute to reduced numbers of faculty members, poor
      remuneration and diminished capabilities for career advancement. Addressing the
      issues currently plaguing academic medicine will enable this essential and multi
      faceted discipline to flourish.

PMID- 15495281
TI  - Family medicine as a model of transition from academic medicine to academic
      health care: Estonia's experience.
AB  - This paper presents the development of academic family medicine in an environment
      of traditional academic medicine at the Tartu University, Estonia. The
      introduction of university family medicine teachers to everyday practice and
      practitioners to academic teaching and research helps bridge the gap between
      theory and practice, and it shows changed approach to academic medicine.

PMID- 15495282
TI  - Does equal availability of geographical and human resources guarantee access to
      family doctors in Estonia?
AB  - AIMS: To describe allocation of posts of trained family doctors geographically;
      to assess the patients' consultation rate and family doctors' workload
      geographically; and to evaluate comprehensiveness of the work of family doctors.
      METHODS: Data for the description of training in family medicine and the system
      of primary health care in Estonia were drawn from the health statistics of the
      Ministry of Social Affairs of Estonia and from data of the Estonian Health
      Insurance Fund. The comprehensiveness of work was expressed as the percentage of
      newborn babies on the practice lists of family doctors out of the total births in
      Estonia during 1999-2002. RESULTS: Altogether 979 doctors became family medicine
      specialists during 1991-2004, which corresponds to Estonia's need--one family
      doctor per 1,600+/-400 inhabitants. The rate of visits to family doctors has
      increased during recent years and in 2002 one inhabitant made 2.7 visits per year
      on average. Family doctors received an average of 22 visits per day throughout
      2002. The number of home visits increased: in 2002 every fifth person and almost
      every second child in Estonia was visited by a doctor. According to the
      registration of newborns on family doctors lists, the comprehensiveness of family
      practice rose: in 2002, 83% of all newborns were registered with family doctors.
      CONCLUSION: The allocation of family doctors geographically according to
      population density ensures access to medical services in their localities. The
      registration of newborns with family doctors shows the comprehensiveness of the
      work of family doctors. Elaboration of the indicators for the analysis of
      accessibility of family doctors services, using national statistics, helps
      evaluate the development and further planning of the primary health care system.

PMID- 15495283
TI  - Efficiency and sustainability of using resources in Estonian primary health care.
AB  - AIM: To assess the efficiency and sustainability of using health resources in
      Estonian primary health care during 1998-2002. Three economic criteria-
      allocative efficiency, technical efficiency, and financial sustainability were
      analyzed from the original set of indicators, in parallel with the analysis of
      the Estonian economic development in 1998-2002. METHOD: Routinely collected data
      from the Estonian Health Insurance Fund, the Department of Statistics and
      Analysis of the Ministry of Social Affairs, and Statistical Office of Estonia
      were used. All together, 22 empirical indicators that cover the most important
      areas of primary health care provision and utilization for the period 1998-2002
      were calculated. RESULTS: Since 1999, Estonian economic growth has been
      approximately 7% each year. In 2000-2002 the average growth of consumer prices
      was approximately 4%. The number of family doctors has increased because the
      relevant education has been provided on a regular basis. Family doctors are using
      both group and solo practice. The size of family doctors' patient lists has
      stabilized, but can still vary between different counties and between countryside
      and towns because of variations in the density of population in different areas.
      The new combined system of financing primary health care provides a financial
      sustainability in using resources in Estonian primary health care. CONCLUSION:
      Similar sets of indicators may prove useful in other countries of Eastern and
      Central Europe which are undergoing rapid changes in their health systems, yet do
      not have the complex health information systems like those in the countries from
      Organisation for Economic Co-operation and Development (OECD), and enable
      comparative analyses between them.

PMID- 15495284
TI  - Patients' opinions on family doctor accessibility in Estonia.
AB  - AIM: To investigate the accessibility of family doctors in Estonia from the
      patients' point of view. METHODS: Face to face interviews using structured
      questionnaires were performed. A random sample of the Estonian residents, aged 15
      74 years, was studied (n=999). RESULTS: The number of visits provided by family
      doctors has been continuously increasing since 1998. Out of 999 respondents, 59%
      visited the family doctor during the previous 12 months. The average number of
      visits per Estonian resident in one year is 2.48. Out of 999 interviewed persons,
      72% said that they had a possibility of contacting their family doctor by phone.
      The waiting time for an appointment was short in most cases. The family doctor
      admitted 60% of the respondents on the same day the patients had requested; 22%
      of the patients were admitted within 1-2 days and 9% of the patients were
      admitted within 3-4 days. Only 9% of them had to wait more than 5 days. The
      current home visit fee in Estonia would have affected the decision of the home
      call of 58% of people. There was a correlation between the acceptability of a
      visit fee and the people's income. CONCLUSION: The accessibility of family
      doctors can be considered good in Estonia.

PMID- 15495285
TI  - Evaluation of primary health care reform in Estonia from patients' perspective:
      acceptability and satisfaction.
AB  - AIM: To analyze the population's view of the primary health care reform five
      years after the formal implementation of the reform investigating the
      acceptability of the primary health care system, patients' preferences, and
      satisfaction with their family doctors. METHODS: Face-to-face interviews using
      structured questionnaires were preformed with a random sample of the Estonian
      residents aged 15-74 years (n=999). RESULTS: Out of 999 respondents, 35% prefer
      to first see their family doctor and if necessary to get a referral or a
      recommendation to see a specialist. The referral to the specialist by the family
      doctor is more preferred by older respondents, rural people, by the respondents
      with a lower level of education and income as well as by people who were more
      satisfied with their family doctor. The people who were more satisfied with their
      family doctor found that the whole health care system was functioning better than
      the previous primary health care system. Out of all the respondents who have had
      a contact with their family doctor during the last 12 months 87% (n=585) were
      satisfied with his work. The overall satisfaction with the family doctor depended
      on 1) perceived competence of the physician (OR=0.624, 95% confidence interval
      (CI)=0.419-0.933); 2) understanding the patient's problem (OR=0.699, 95%CI=0.496
      0.984); 3) punctuality of the physician (OR=1.533, 95%CI=1.075-2.186); and 4) the
      location of the primary health care center/clinic (OR=0.751, 95%CI=0.574-0.983).
      CONCLUSION: During the five-year-period most of the Estonian population has
      accepted the new primary health care system and the satisfaction rate has
      increased. Family doctors are in the center of the primary health care systems
      and their professional competence plays a great role in making the system
      acceptable for the patients.

PMID- 15495286
TI  - Rheumatic patients in primary and secondary care: differences in structure of
      diagnoses and working load within a five-year period.
AB  - AIM: To compare conditions handled by family doctors and rheumatologists and
      analyze changes in the distribution of work between primary and secondary care.
      METHODS: The study population consisted of patients listed with five family
      doctors. The number and structure of patients with rheumatic diseases and
      dynamics of visits were examined on the basis of yearly reports dating from 1999
      to 2003. Statistics for 1999-2003 were analyzed to provide a background for data
      concerning outpatient rheumatic care at the University Hospital. A 2-month survey
      of all consecutive patients referred to rheumatology outpatient center was
      performed. RESULTS: The number of visits per patient to a family doctor has
      decreased to 3.0 in 2003 while the number of visits of rheumatic patients to
      family doctors has increased to 5.9. In 2003 rheumatic patients made up 16.9% of
      all family doctors' patients, while their number of visits constituted 33.5% of
      the total visits to a family doctor. The share of visits to a family doctor by
      rheumatoid arthritis patients has decreased, whereas the share of patients with
      osteoarthritis has increased. Waiting time for a specialist appointment in 2004
      does not exceed three weeks. Out of all the patients referred to rheumatologists,
      31.2% were patients with rheumatoid arthritis and 10.4% with osteoarthritis.
      Patients assessed the availability of rheumatologists as excellent in 47% of
      cases. CONCLUSION: Since a new model of primary health care was implemented, the
      division of work between primary and secondary care has been rearranged and
      currently corresponds to the patient structure and available resources in
      outpatient care.

PMID- 15495287
TI  - Evaluation of symptom presentation in dyspeptic patients referred for upper
      gastrointestinal endoscopy in Estonia.
AB  - AIM: To investigate the structure of dyspeptic symptoms and determine the
      association between dyspeptic symptoms and endoscopic findings in patients
      referred for upper gastrointestinal endoscopy by family physicians in a country
      with a high prevalence of Helicobacter pylori infection. METHODS: Consecutive
      outpatients (n=172; median 36 years, range 18-75; 85 male; 87 female) were
      referred to upper gastrointestinal endoscopy. Patient history was recorded prior
      to upper gastrointestinal endoscopy using the computer-aided Glasgow Diagnostic
      System for Dyspepsia (GLADYS). Family physicians used open access endoscopy with
      a short waiting list. Two biopsies, both from the antrum and the corpus, were
      taken for histological assessment. RESULTS: Out of the 172 patients studied, 81%
      (n=139) were H. pylori positive, 65% (n=112) were younger than 45 years. The
      incidence of peptic ulcer was 44% (n=75). Upper abdominal pain was the
      predominant complaint in 73% (n=126) of the patients, as well as the most
      frequent overall complaint. Hunger pain, night pain, periodical nature of
      symptoms, and history over 2 years were of independent value in differentiating
      between peptic ulcer and functional dyspepsia. The symptoms of gastroesophageal
      reflux disease and irritable bowel syndrome predominated in the minority of
      patients (11% and 5% respectively) but accompanied other complaints in almost 2/3
      of the patients. In 32 out of 75 patients with peptic ulcer, the symptoms of
      irritable bowel syndrome and in 29 cases the presence of frequent heartburn and
      regurgitation were noted. CONCLUSIONS: Classical symptoms are valuable in
      predicting the diagnosis of peptic ulcer. Heartburn and acid regurgitation are
      present in both gastroesophageal reflux disease and peptic ulcer. Irritable bowel
      syndrome is common in patients with peptic ulcer.

PMID- 15495288
TI  - Seeking quality improvement in primary care in Crete, Greece: the first actions.
AB  - AIM: To implement quality improvement programs and assess the clinical
      effectiveness within the primary care setting. METHODS: The introduction of
      clinical governance teams, the establishment of a patient-based record system,
      and the dissemination of practice guidelines were included among the efforts made
      to improve the quality of care. The clinical effectiveness was measured using
      EUROPEP (European Task Force on Patient Evaluations of General Practice tool) for
      evaluating patient's opinion and contracts between health authorities and primary
      care physicians and nurses. RESULTS: Clinical governance teams of 5-6
      practitioners were formed in all health centers. Health cards were created for
      6,150 individuals, and a high satisfaction rate with the interest in the
      patient's personal situation (97.6% of participants assessed it as excellent),
      physical examination (97.6%), and giving information about symptoms and illness
      (97.6%) was recorded on the EUROPEP sample. Lack of infrastructure and diagnostic
      equipment were considered as important barriers in implementing contracts in
      primary care. CONCLUSION: Primary health care in a rural setting in Crete is
      engaged in setting up systems for implementing clinical governance and quality
      programs. The Regional Authorities of Health and Welfare should provide further
      support.

PMID- 15495289
TI  - New general practitioner payment formula in Croatia: is it consistent with
      worldwide trends?
AB  - We describe the history of general practitioner payment in Croatia, and assess
      the extent to which recent trends are consistent with developments in other
      countries. We provide a definition of a classification of payment methods, and
      summarization of the evidence about their merits as described in international
      literature and an outline of the history of payment methods in Croatia, with
      emphasis on the changes proposed for 2004. We conclude that the introduction of
      performance-based payment, as an adjunct to the capitation payments, is
      consistent with trends in well-managed health systems in other countries.
      However, we argue that the changes need to be incorporated into a long-term
      strategy, and we suggest some elements including refinement of the capitation
      payment risk adjustment.

PMID- 15495290
TI  - Croatian pharmaceutical sector reform project: rational drug use.
AB  - The Croatian Pharmaceutical Sector Reform Project was one component of a larger
      Health Reform Project financed by the World Bank. The Croatian government was
      concerned that Croatia appeared to spend more money on medicinal drugs than most
      other countries in the region; that the price of drugs purchased in Croatia was
      higher than in some other countries, and that the prescribing habits of some
      Croatian physicians were perceived to be unnecessarily expensive. In addition,
      the Croatian Institute for Health Insurance (CIHI), which pays for most health
      care, had come under considerable financial pressure due to increasing health
      expenditure and a decreasing proportion of the population contributing to
      insurance. The Australian Health Insurance Commission won the contract for the
      pharmaceutical reform project. Australian experts were matched with Croatian
      experts in order to share knowledge, learn from each other, and provide the best
      advice. The project had two main components. The first addressed supply side
      issues and provided advice about savings that could be made by incorporating
      pharmacoeconomic principles into the selection and purchase of drugs on the
      Croatian positive list. The second component addressed demand side issues and
      provided advice aimed at evaluating and improving the quality and effectiveness
      of drug prescribing by Croatian physicians. This paper describes the second
      project component. We quantitatively and qualitatively evaluated the prescribing
      practice of Croatian physicians and ascertain how these might be improved.
      Croatian general practitioners are required to enter an International
      Classification of Diseases, 10th Revision (ICD10) diagnostic code on their
      prescription in order to indicate the clinical problem being treated.
      Quantitative research involved sorting CIHI prescription data for 2002 into ICD10
      diagnostic categories and comparing the drugs prescribed for particular
      conditions with the recommendations in local and international best-practice
      guidelines. The results showed a number of areas where the prescribing of
      Croatian general practitioners and specialists could be improved, such as the use
      of antibiotics in upper respiratory tract infections and the treatment of
      hypertension. Qualitative research involved a series of workshops with local
      pharmacological experts and general practitioners during which the collected
      prescribing data was discussed, local factors which influenced prescribing were
      explored, and suggestions for improvement were collated. Many general
      practitioners felt pressured by increasingly assertive consumers, relentless
      pharmaceutical promotion, and strident government (CIHI) demands to restrain
      escalating health care costs. In addition, there was a lack of information about
      what constituted cost-effective treatment appropriate to the Croatian economic
      situation. There was support for the production of concise Croatian therapeutic
      guidelines that provided a limited number of best-practice treatment options for
      common conditions. A pilot set of such guidelines was devised and incorporated
      into a clinical software trialed in a Primary Health Care Information Technology
      Project in Koprivnica. This initiative received support from the general
      practitioners involved. It was recommended that a unit for the quality use of
      medicines should be set up to sustain the production of therapeutic guidelines
      and coordinate this activity with related initiatives. In addition, a quality
      assurance system (including performance indicators linked to financial
      incentives) was recommended that would encourage general practitioners to
      practice in accord with guidelines. We understand that the Croatian government
      has accepted a number of these recommendations and, in particular, performance
      indicators (and financial incentives) are written into new contracts for Croatian
      general practitioners in 2004.

PMID- 15495291
TI  - Frequent attenders in family practice in Croatia: retrospective study.
AB  - AIM: To determine the number of "frequent attenders" in family practice offices
      in Croatia according to the number and proportion of frequent attender visits in
      the total number of visits, and to follow up the frequent attenders and the
      number of visits they made over a period of three years. METHODS: The
      retrospective study involved 8 family practice offices in Northern Croatia. The
      number of visits to family practice was determined for 4,312 patients aged over
      18 years. There were 1,826 men (42.3%) and 2,486 (57.7%) women. The follow up
      period lasted from January 1, 1997 to December 31, 1999. The borderline value
      that divided the frequent from non-frequent attenders was the value at the third
      quartile of the number of visits in a single age-sex group of patients. RESULTS:
      We recorded a total of 58,088 visits of patients older than 18 years to 8 family
      practice offices in the three-year period. In 1997, out of 4,312 patients who
      made a total of 17,938 visits, 944 (22%) frequent attenders made 11,257 (63%)
      visits. In 1998, there were a total of 20,350 visits made, with 966 (22%)
      frequent attenders making 12,145 (60%) visits. In 1999, a total of 20,725 visits
      were made, with 988 (23%) frequent attenders making 12,259 (59%) visits. The
      differences in the distribution of frequent vs non-frequent attenders according
      to age and sex were not statistically significant in any of the three study years
      (chi-square, p=0.727). Older men and older women were not more often frequent
      attenders than younger men and younger women, respectively. Out of 4,312
      patients, 1,714 (40%) were frequent attenders in one of the three study years. Of
      these, 884 (21%) were frequent attenders in one year, 476 (11%) in two years, and
      354 (8%) in all three subsequent study years. Out of 4,312 patients, 1,762 (41%)
      patients in 1997, 1,139 (26%) in 1998, and 1,116 (26%) patients in 1999 did not
      make a single visit to a family physician. CONCLUSION: Frequent attender visits
      make a great proportion of the total number of visits to family practice offices
      in Croatia, a country with a health care system in transition. Eight percent of
      patients remained being frequent attenders during all three study years.

PMID- 15495292
TI  - Education about pharmacotherapy and psychotherapy of anxiety among primary care
      physicians in Croatia: Balint group approach.
AB  - AIM: Balint groups help general practitioners to be sensitive to the
      psychological needs of anxiety patients and cope with their stress and mental
      health. We evaluated knowledge about pharmacotherapy and psychotherapy of anxiety
      among Croatian primary care physicians before and after a course based on Balint
      group methodology. METHODS: There were 111 primary care physicians (general
      practitioners and specialists in general practice) who attended the Balint course
      as a part of their continuous education during 2003. Course participants answered
      questions on pharmacotherapy and psychotherapy of anxiety before and after the
      course. RESULTS: At the beginning of the course, there were significantly more
      specialists in general practice who gave correct answers on definition of
      anxiolytics and about their side effects (chi-square test, p=0.046 and p=0.030,
      respectively). Before the course, high number of physicians in both groups agreed
      that psychotherapy could be used by non-psychiatrists (70-80%, no significant
      difference), but after the course significantly more specialists in general
      practice were aware that supportive psychotherapy could be used in general
      practice (chi-square test, p=0.002). Before the course significantly more
      specialists in general practice knew that only supportive psychotherapy can be
      used in general practice (chi-square test, p=0.010), but after the course general
      practitioners' correct answers increased and the difference was not significant.
      Daily usage of psychotherapy before the course was significantly more frequent
      among specialists (chi-square test, p<0.001), but this difference disappeared
      after the course. Number of general practitioners who never used psychotherapy
      decreased after the course (chi-square=4.83, d.f.=1, p=0.028). Linear regression
      analysis revealed female sex to be a significant predictor for the positive
      effects of the course (B=0.71, p=0.025). CONCLUSION: The Balint course
      significantly reduced differences in knowledge of pharmacotherapy and
      psychotherapy of anxiety between specialists in general practice and general
      practitioners and improved prospects for the practice of psychotherapy among
      general practitioners.

PMID- 15495293
TI  - Obstacles which patients with type 2 diabetes meet while adhering to the
      therapeutic regimen in everyday life: qualitative study.
AB  - AIM: To explore type 2 diabetic patients' attitudes, thoughts, and fears
      connected with their illness; their expectations of the health care system; and
      the problems they encountered while adhering to the therapeutic regimen. METHOD:
      Explanatory descriptive focus groups were held with 49 type 2 diabetic patients.
      Patients were recruited by their general/family practitioners and divided into
      seven focus groups. The group discussions were audio taped and transcribed, then
      analyzed to find emerging themes and sub-themes. Textual data were explored
      inductively using content analysis to generate categories and explanations.
      Hypotheses were derived from the qualitative content analysis. RESULTS: Eight
      major themes and explanatory models of patient's perspective emerged out of the
      data: confronting the diagnosis, illness-related changes, treatment of illness,
      social context, relation to the health professionals, self-control, knowledge
      about the illness, and expectations from health professionals. Health beliefs,
      quality of the doctor-patient relationship, social environment of the family,
      workplace, health care system, and quality of the information they receive from
      health professionals and media were all important factors in patient adherence.
      CONCLUSIONS: There were many obstacles for bettering patients adhering to the
      therapeutic regimen, as from the patients' socio-economical aspect, and in the
      existing health system of Croatia as well. Providing of updated information about
      the disease, empathy and support of physicians can improve adherence to
      treatment.

PMID- 15495294
TI  - Interregional differences in health in Slovenia. I. Estimated prevalence of
      selected cardiovascular and related diseases.
AB  - AIM: To determine estimates of prevalence of selected cardiovascular and related
      diseases (myocardial and brain infarction, angina pectoris, hypertension,
      diabetes, and obesity) in western, central, and eastern regions of Slovenia.
      METHODS: A national survey on health status and health behavior of the adult
      population included 15,379 Slovene inhabitants, aged 25-64. The overall response
      rate to a mailed questionnaire was 63,8%, and finally 9,043 questionnaires were
      eligible for analysis. The prevalence rates per 100 of population were
      determined, and chi-square test was used for global assessment of interregional
      prevalence differences. Logistic regression was carried out for sex and age
      adjusted assessment. RESULTS: The highest prevalence was confirmed in eastern
      Slovenia and the lowest in western Slovenia, with the exception of myocardial
      infarction, whose prevalence was lowest in central Slovenia. Differences were
      statistically significant for brain infarction (west: 0.5, center: 0.8, east:
      1.1; p=0.045), angina pectoris (west: 3.5, center: 5.0, east: 6.9; p<0.001),
      hypertension (west: 15.6, center: 19.2, east: 20.0; p<0.001), and obesity (west:
      12.5, center: 14.1, east: 16.8; p<0.001), but not in myocardial infarction (west:
      1.3, center: 1.2, east: 1.5; p=0.583) and diabetes (west: 3.5, center: 4.5, east:
      4.6; p=0.097). CONCLUSION: Our study globally confirmed the hypothesis of
      existence of interregional differences in the prevalence of selected
      cardiovascular and related diseases.

PMID- 15495295
TI  - Interregional differences in health in Slovenia. II. Estimated prevalence of
      selected behavioral risk factors for cardiovascular and related diseases.
AB  - AIM: To estimate the prevalence of selected behavioral risk factors for
      cardiovascular and related diseases in western, central, and eastern region of
      Slovenia and to determine interregional differences. METHODS: A national survey
      on health status and health behavior of the adult population included 15,379
      Slovene inhabitants, aged 25 to 64. The overall response rate to a mailed
      questionnaire was almost 64%, and 9,043 questionnaires were eligible for
      analysis. Prevalence rates per 100 population (smoking, nutrition, alcohol
      intake, physical activity, stress) were determined, chi-square test was used for
      global assessment of interregional differences, and logistic regression for
      adjusting them for sex and age. RESULTS: Interregional differences in prevalence
      were observed in very unhealthy nutrition related to obesity and diabetes (west:
      34.0, center: 30.6, east: 41.8; p<0.001), very unhealthy nutrition related to
      hypertension (west: 25.5, center: 29.4, east: 28.4; p=0.011), very unhealthy
      nutrition related to atherosclerosis-based diseases (angina pectoris, myocardial
      and brain infarction, etc.) (west: 33.1, center: 31.8, east: 44.1; p<0.001),
      heavy alcohol drinking (west: 11.2, center: 12.0, east: 15.2; p<0.001), and
      physical inactivity (west: 18.0, center: 21.0, east: 15.3; p<0.001), but not in
      smoking (west: 22.4, center: 24.5, east: 23.9; p=0.230) or stress (west: 23.2,
      center: 24.4, east: 24.7; p=0.388). CONCLUSION: We confirmed significant
      interregional differences in the prevalence of most observed behavioral risk
      factors. In behaviors with statistically significant interregional differences,
      the highest prevalence was confirmed for eastern Slovenia.

PMID- 15495296
TI  - Patient satisfaction in dental outpatient clinics in Turkey.
AB  - AIM: To measure the level of patient satisfaction in the dental outpatient
      clinics from a group of state hospitals in Turkey and explore the factors that
      may influence satisfaction. METHODS: In a cross-sectional study, patients
      attending the outpatient clinics state hospitals from 9 provinces were
      interviewed. Data regarding socio-demographic characteristics of the respondents
      were collected and a patient satisfaction questionnaire, which consisted of 29
      statements regarding various aspects of satisfaction, were completed during face
      to-face interviews (n=641, response rate 89%). RESULTS: There was no difference
      between the mean satisfaction scores of the study group with regard to socio
      demographic characteristics except for the type of health insurance held by the
      patient. Patients covered by state pension funds had significantly higher
      satisfaction scores than the self-employed group with public insurance. Patients
      were most satisfied with privacy (82.1% of the respondents). Waiting time was the
      least satisfactory issue, with only 41.8% of patients reporting satisfaction with
      waiting time. CONCLUSION: The type of health insurance of the patients seems to
      be a significant predictor of dental patient satisfaction in Turkish state
      hospitals. Privacy was the most satisfactory service attribute whereas the
      waiting time had the lowest satisfactory rating.

PMID- 15495297
TI  - 200th anniversary (1804-2004) of the publication of the poem: Vaccinatio; De
      Jenneriano invento optime merito; Carmen elegiacum; by Croatian scientist Luko
      Stulli.
AB  - Luko Stulli (1772-1828) was a physician who in 1800 performed the first
      vaccination in Dubrovnik. He was one of the last Latin poets in the Croatian
      literature. In 1804, Stulli wrote the poem Vaccinaio; De Jenneriano invento
      optime merito; Carmen elegiacum (Vaccination; On the Outstanding Jennerian
      Invention; Elegiac Poem). Thus, the vaccination effort in Dubrovnik has a
      historical and a literary significance. This paper presents a critical reading of
      the poem Vaccinatio by Luko Stulli, together with important medical historical
      and literary background relevant to it. The complete, original Latin poem and its
      English and Croatian translation are found in the appendix of the article (p.
      661).

PMID- 15495298
TI  - The ways of being almost perfect.

PMID- 15495300
TI  - Quality of primary care.

PMID- 15495301
TI  - A characteristic condition of finite nilpotent group.
AB  - This paper gives a characteristic condition of finite nilpotent group under the
      assumption that all minimal subgroups of G are well-suited in G.

PMID- 15495302
TI  - A general version of the Morse-Sard theorem.
AB  - Let k, m, n be positive integers, and k> or =2, alphain(0,1], 0<r<min[m,n] an
      integer, d=r+(m-r)/(k+alpha), and if finC(k,alpha)(Rm, Rn),
      A=Cr(f)=[xinRm|rank(Df(x))< or =r], then f(A) is d-null. Thus the statement posed
      by Arthur Sard in 1965 can be completely solved when k> or =2.

PMID- 15495303
TI  - Extreme points of norm closed nest algebra modules.
AB  - Suppose that U is a norm closed nest algebra module. Using the characterization
      of rank one operators in U perpendicular, a complete description of the extreme
      points of the unit ball U1 is given.

PMID- 15495304
TI  - A flower image retrieval method based on ROI feature.
AB  - Flower image retrieval is a very important step for computer-aided plant species
      recognition. In this paper, we propose an efficient segmentation method based on
      color clustering and domain knowledge to extract flower regions from flower
      images. For flower retrieval, we use the color histogram of a flower region to
      characterize the color features of flower and two shape-based features sets,
      Centroid-Contour Distance (CCD) and Angle Code Histogram (ACH), to characterize
      the shape features of a flower contour. Experimental results showed that our
      flower region extraction method based on color clustering and domain knowledge
      can produce accurate flower regions. Flower retrieval results on a database of
      885 flower images collected from 14 plant species showed that our Region-of
      Interest (ROI) based retrieval approach using both color and shape features can
      perform better than a method based on the global color histogram proposed by
      Swain and Ballard (1991) and a method based on domain knowledge-driven
      segmentation and color names proposed by Das et al.(1999).

PMID- 15495305
TI  - Developing rigid constraint for the estimation of pose and structure from a
      single image.
AB  - Pose and structure estimation from a single image is a fundamental problem in
      machine vision and multiple sensor fusion and integration. In this paper we
      propose using rigid constraints described in different coordinate frames to
      iteratively estimate structural and camera pose parameters. Using geometric
      properties of reflected correspondences we put forward a new concept, the
      reflected pole of a rigid transformation. The reflected pole represents a general
      analysis of transformations that can be applied to both 2D and 3D
      transformations. We demonstrate how the concept is applied to calibration by
      proposing an iterative method to estimate the structural parameters of objects.
      The method is based on a coarse-to-fine strategy in which initial estimation is
      obtained through a classical linear algorithm which is then refined by iteration.
      For a comparative study of performance, we also implemented an extended motion
      estimation algorithm (from 2D-2D to 3D-2D case) based on epipolar geometry.

PMID- 15495306
TI  - Automated soil resources mapping based on decision tree and Bayesian predictive
      modeling.
AB  - This article presents two approaches for automated building of knowledge bases of
      soil resources mapping. These methods used decision tree and Bayesian predictive
      modeling, respectively to generate knowledge from training data. With these
      methods, building a knowledge base for automated soil mapping is easier than
      using the conventional knowledge acquisition approach. The knowledge bases built
      by these two methods were used by the knowledge classifier for soil type
      classification of the Longyou area, Zhejiang Province, China using TM bi-temporal
      imageries and GIS data. To evaluate the performance of the resultant knowledge
      bases, the classification results were compared to existing soil map based on
      field survey. The accuracy assessment and analysis of the resultant soil maps
      suggested that the knowledge bases built by these two methods were of good
      quality for mapping distribution model of soil classes over the study area.

PMID- 15495307
TI  - A matching algorithm based on hybrid matrices consisting of reference differences
      and disparities.
AB  - Unique correct correspondence cannot be obtained only by use of gray correlation
      technique, which describes gray similar degree of feature points between the left
      and right images too unilaterally. The gray correlation technique is adopted to
      extract gray correlation peaks as a coarse matching set called multi-peak set.
      The disparity gradient limited constraint is utilized to optimize the multi-peak
      set. Unique match will be obtained by calculating the correlation of hybrid
      matrices consisting of reference differences and disparities from the multi-peak
      set. Two of the known corresponding points in the left and right images,
      respectively, are set as a pair of reference points to determine search direction
      and search scope at first. After the unique correspondence is obtained by
      calculating the correlation of the hybrid matrices from the multi-peak set, the
      obtained match is regarded as a new reference point till all feature points in
      the left (or right) image have been processed. Experimental results proved that
      the proposed algorithm was feasible and accurate.

PMID- 15495308
TI  - Decryption of pure-position permutation algorithms.
AB  - Pure position permutation image encryption algorithms, commonly used as image
      encryption investigated in this work are unfortunately frail under known-text
      attack. In view of the weakness of pure position permutation algorithm, we put
      forward an effective decryption algorithm for all pure-position permutation
      algorithms. First, a summary of the pure position permutation image encryption
      algorithms is given by introducing the concept of ergodic matrices. Then, by
      using probability theory and algebraic principles, the decryption probability of
      pure-position permutation algorithms is verified theoretically; and then, by
      defining the operation system of fuzzy ergodic matrices, we improve a specific
      decryption algorithm. Finally, some simulation results are shown.

PMID- 15495309
TI  - A minimal axiom group for rough set based on quasi-ordering.
AB  - Rough set axiomatization is one aspect of rough set study to characterize rough
      set theory using dependable and minimal axiom groups. Thus, rough set theory can
      be studied by logic and axiom system methods. The classic rough set theory is
      based on equivalent relation, but rough set theory based on reflexive and
      transitive relation (called quasi-ordering) has wide applications in the real
      world. To characterize topological rough set theory, an axiom group named RT,
      consisting of 4 axioms, is proposed. It is proved that the axiom group
      reliability in characterizing rough set theory based on similar relation is
      reasonable. Simultaneously, the minimization of the axiom group, which requires
      that each axiom is an equation and each is independent, is proved. The axiom
      group is helpful for researching rough set theory by logic and axiom system
      methods.

PMID- 15495310
TI  - An integrated DBP for streams with (m, k)-firm real-time guarantee.
AB  - (m, k)-firm real-time or weakly hard real-time (WHRT) guarantee is becoming
      attractive as it closes the gap between hard and soft (or probabilistic) real
      time guarantee, and enables finer granularity of real-time QoS through adjusting
      m and k. For multiple streams with (m, k)-firm constraint sharing a single
      server, an on-line priority assignment policy based on the most recent k-length
      history of each stream called distance based priority (DBP) has been proposed to
      assign priority. In case of priority equality among these head-of-queue
      instances, Earliest Deadline First (EDF) is used. Under the context of WHRT
      schedule theory, DBP is the most popular, gets much attention and has many
      applications due to its straightforward priority assignment policy and easy
      implementation. However, DBP combined with EDF cannot always provide good
      performance, mainly because the initial DBP does not underline the rich
      information on deadline met/missed distribution, specially streams in various
      failure states which will travel different distances to restore success states.
      Considering how to effectively restore the success state of each individual
      stream from a failure state, an integrated DBP utilizing deadline met/missed
      distribution is proposed in this paper. Simulation results validated the
      performance improvement of this proposal.

PMID- 15495311
TI  - Mixed Gl2/GH2 multi-channel multi-objective control synthesis for discrete time
      systems.
AB  - This paper proposes a new approach for multi-objective robust control. The
      approach extends the standard generalized l2 (Gl2) and generalized H2 (GH2)
      conditions to a set of new linear matrix inequality (LMI) constraints based on a
      new stability condition. A technique for variable parameterization is introduced
      to the multi-objective control problem to preserve the linearity of the synthesis
      variables. Consequently, the multi-channel multi-objective mixed Gl2/GH2 control
      problem can be solved less conservatively using computationally tractable
      algorithms developed in the paper.

PMID- 15495312
TI  - Cellular automata modeling of pedestrian's crossing dynamics.
AB  - Cellular automata modeling techniques and the characteristics of mixed traffic
      flow were used to derive the 2-dimensional model presented here for simulation of
      pedestrian's crossing dynamics. A conception of "stop point" is introduced to
      deal with traffic obstacles and resolve conflicts among pedestrians or between
      pedestrians and the other vehicles on the crosswalk. The model can be easily
      extended, is very efficient for simulation of pedestrian's crossing dynamics, can
      be integrated into traffic simulation software, and has been proved feasible by
      simulation experiments.

PMID- 15495313
TI  - Delay-dependent robust H infinity control for a class of uncertain switched
      systems with time delay.
AB  - For linear switched system with both parameter uncertainties and time delay, a
      delay-dependent sufficient condition for the existence of a new robust H infinity
      feedback controller was formulated in nonlinear matrix inequalities solvable by
      an LMI-based iterative algorithm. Compared with the conventional state-feedback
      controller, the proposed controller can achieve better robust control performance
      since the delayed state is utilized as additional feedback information and the
      parameters of the proposed controllers are changed synchronously with the
      dynamical characteristic of the system. This design method was also extended to
      the case where only delayed state is available for the controller. The example of
      balancing an inverted pendulum on a cart demonstrates the effectiveness and
      applicability of the proposed design methods.

PMID- 15495314
TI  - Swarm intelligence for mixed-variable design optimization.
AB  - Many engineering optimization problems frequently encounter continuous variables
      and discrete variables which adds considerably to the solution complexity. Very
      few of the existing methods can yield a globally optimal solution when the
      objective functions are non-convex and non-differentiable. This paper presents a
      hybrid swarm intelligence approach (HSIA) for solving these nonlinear
      optimization problems which contain integer, discrete, zero-one and continuous
      variables. HSIA provides an improvement in global search reliability in a mixed
      variable space and converges steadily to a good solution. An approach to handle
      various kinds of variables and constraints is discussed. Comparison testing of
      several examples of mixed-variable optimization problems in the literature showed
      that the proposed approach is superior to current methods for finding the best
      solution, in terms of both solution quality and algorithm robustness.

PMID- 15495315
TI  - Carrier phase shifted SPWM based on current sourced multi-modular converter for
      active power filter.
AB  - A novel current-source active power filter (APF) based on multi-modular converter
      with carrier phase-shifted SPWM (CPS-SPWM) technique is proposed. With this
      technique, the effect of equivalent high switching frequency converter is
      obtained with low switching frequency converter. It is very promising in current
      source APF that adopt superconducting magnetic energy storage component.

PMID- 15495316
TI  - Adaptive swarm-based routing in communication networks.
AB  - Swarm intelligence inspired by the social behavior of ants boasts a number of
      attractive features, including adaptation, robustness and distributed,
      decentralized nature, which are well suited for routing in modern communication
      networks. This paper describes an adaptive swarm-based routing algorithm that
      increases convergence speed, reduces routing instabilities and oscillations by
      using a novel variation of reinforcement learning and a technique called
      momentum. Experiment on the dynamic network showed that adaptive swarm-based
      routing learns the optimum routing in terms of convergence speed and average
      packet latency.

PMID- 15495317
TI  - Bipolaron in different configuration of quantum confinement.
AB  - The authors used Landau-Pekar variational method to investigate a strong-coupling
      singlet optical bipolaron in different configuration of quantum confinement.
      Numerical and analytical results showed that when configuration changes from
      quantum dot and wire to well, confinement shows different effect on the formation
      of a bipolaron. In contrast to a bipolaron in a quantum dot or wire, the binding
      energy of a bipolaron in a quantum well increases with increasing confinement,
      indicating that confinement favors bipolaron formation in a quantum well.

PMID- 15495318
TI  - Study on shift schedule saving energy of automatic transmission of ground
      vehicles.
AB  - To improve ground vehicle efficiency, shift schedule energy saving was proposed
      for the ground vehicle automatic transmission by studying the function of the
      torque converter and transmission in the vehicular drivetrain. The shift schedule
      can keep the torque converter working in the high efficiency range under all the
      working conditions except in the low efficiency range on the left when the
      transmission worked at the lowest shift, and in the low efficiency range on the
      right when the transmission worked at the highest shift. The shift quality key
      factors were analysed. The automatic trans-mission's bench-test adopting this
      shift schedule was made on the automatic transmission's test-bed. The
      experimental results showed that the shift schedule was correct and that the
      shift quality was controllable.

PMID- 15495319
TI  - Numerical method to determine mechanical parameters of engineering design in rock
      masses.
AB  - This paper proposes a new continuity model for engineering in rock masses and a
      new schematic method for reporting the engineering of rock continuity. This
      method can be used to evaluate the mechanics of every kind of medium; and is a
      new way to determine the mechanical parameters used in engineering design in rock
      masses. In the numerical simulation, the experimental parameters of intact rock
      were combined with the structural properties of field rock. The experimental
      results for orthogonally-jointed rock are given. The results included the curves
      of the stress-strain relationship of some rock masses, the curve of the
      relationship between the dimension Delta and the uniaxial pressure-resistant
      strength sc of these rock masses, and pictures of the destructive procedure of
      some rock masses in uniaxial or triaxial tests, etc. Application of the method to
      engineering design in rock masses showed the potential of its application to
      engineering practice.

PMID- 15495320
TI  - Mathematical model of cylindrical form tolerance.
AB  - Tolerance is essential for integration of CAD and CAM. Unfortunately, the meaning
      of tolerances in the national standard is expressed in graphical and language
      forms and is not adaptable for expression, processing and data transferring with
      computers. How to interpret its semantics is becoming a focus of relevant
      studies. This work based on the mathematical definition of form tolerance in ANSI
      Y14.5.1M-1994, established the mathematical model of form tolerance for
      cylindrical feature. First, each tolerance in the national standard was
      established by vector equation. Then on the foundation of tolerance's
      mathematical definition theory, each tolerance zone's mathematical model was
      established by inequality based on degrees of feature. At last the variance area
      of each tolerance zone is derived. This model can interpret the semantics of form
      tolerance exactly and completely.

PMID- 15495321
TI  - On stochastic optimal control of partially observable nonlinear quasi Hamiltonian
      systems.
AB  - A stochastic optimal control strategy for partially observable nonlinear quasi
      Hamiltonian systems is proposed. The optimal control forces consist of two parts.
      The first part is determined by the conditions under which the stochastic optimal
      control problem of a partially observable nonlinear system is converted into that
      of a completely observable linear system. The second part is determined by
      solving the dynamical programming equation derived by applying the stochastic
      averaging method and stochastic dynamical programming principle to the completely
      observable linear control system. The response of the optimally controlled quasi
      Hamiltonian system is predicted by solving the averaged Fokker-Planck-Kolmogorov
      equation associated with the optimally controlled completely observable linear
      system and solving the Riccati equation for the estimated error of system states.
      An example is given to illustrate the procedure and effectiveness of the proposed
      control strategy.

PMID- 15495322
TI  - Time-dependent response of laminated isotropic strips with viscoelastic
      interfaces.
AB  - The two dimensional problem of simply supported laminated isotropic strips with
      viscoelastic interfaces and under static loading was studied. Exact solution was
      derived based on the exact elasticity equation and the Kevin-Voigt viscoelastic
      interfacial model. Numerical computations were performed for a strip consisting
      of three layers of equal thickness. Results indicated that the response of the
      laminate was very sensitive to the presence of viscoelastic interfaces.

PMID- 15495323
TI  - How to realize a negative refractive index material at the atomic level in an
      optical frequency range?
AB  - The theoretical mechanism for realizing a negative refractive index material in
      an optical frequency range with an atomic gas system of electromagnetically
      induced transparency (EIT) is studied. It is shown that under certain conditions
      such a dense gas can exhibit simultaneously negative permittivity and negative
      permeability, and negligibly small loss.

PMID- 15495324
TI  - Model-based testing with UML applied to a roaming algorithm for bluetooth
      devices.
AB  - In late 2001, the Object Management Group issued a Request for Proposal to
      develop a testing profile for UML 2.0. In June 2003, the work on the UML 2.0
      Testing Profile was finally adopted by the OMG. Since March 2004, it has become
      an official standard of the OMG. The UML 2.0 Testing Profile provides support for
      UML based model-driven testing. This paper introduces a methodology on how to use
      the testing profile in order to modify and extend an existing UML design model
      for test issues. The application of the methodology will be explained by applying
      it to an existing UML Model for a Bluetooth device.

PMID- 15495325
TI  - A novel OFDM transmission scheme with length-adaptive Cyclic Prefix.
AB  - Conventional OFDM transmission system uses a fixed-length Cyclic Prefix to
      counteract Inter-Symbol Interferences (ISI) caused by channel delay spreading
      under wireless mobile environment. This may cause considerable performance
      deterioration when the CP length is less than the channel RMS delay spread, or
      may decrease the system power and spectrum efficiency when it is much larger. A
      novel OFDM transmission scheme is proposed in this paper to adapt the CP length
      to the variation of channel delay spread. AOFDM-VCPL utilizes the preamble or
      pilot sub-carriers of each OFDM packet to estimate the channel RMS delay spread;
      and then uses a criterion to calculate the CP length , which finally affects the
      OFDM transmitter. As illustrated in the simulation section, by deploying this
      scheme in a typical wireless environment, the system can transmit at data rate
      11.5 Mb/s higher than conventional non-adaptive system while gaining a 0.65 dB
      power saving at the same BER performance.

PMID- 15495326
TI  - A novel self-organizing E-Learner community model with award and exchange
      mechanisms.
AB  - How to share experience and resources among learners is becoming one of the
      hottest topics in the field of E-Learning collaborative techniques. An intuitive
      way to achieve this objective is to group learners which can help each other into
      the same community and help them learn collaboratively. In this paper, we
      proposed a novel community self-organization model based on multi-agent
      mechanism, which can automatically group learners with similar preferences and
      capabilities. In particular, we proposed award and exchange schemas with
      evaluation and preference track records to raise the performance of this
      algorithm. The description of learner capability, the matchmaking process, the
      definition of evaluation and preference track records, the rules of award and
      exchange schemas and the self-organization algorithm are all discussed in this
      paper. Meanwhile, a prototype has been built to verify the validity and
      efficiency of the algorithm. Experiments based on real learner data showed that
      this mechanism can organize learner communities properly and efficiently; and
      that it has sustainable improved efficiency and scalability.

PMID- 15495327
TI  - TCP-Rab: a receiver advertisement based TCP protocol.
AB  - With the evolution of network technologies, the deficiencies of TCP protocol are
      becoming more and more distinct. The new TCP implementation, called Receiver
      Advertisement Based TCP (TCP-Rab) proposed here to eliminate these deficiencies,
      adopts two basic mechanisms: (1) Bandwidth Estimation and (2) Immediate Recovery.
      Bandwidth estimation is carried out at the receiver, and the result is sent back
      to the sender via the acknowledgements. Immediate Recovery guarantees high
      performance even in lossy link. Rab can distinguish the reason for packet loss,
      and thus adopt appropriate recovery strategy. For loss by network congestion, it
      will back off its congestion window, and for loss by link errors, it will recover
      the congestion window immediately. Simulations indicated that Rab has superiority
      over other TCP implementations.

PMID- 15495328
TI  - An adaptive mechanism to guarantee the bandwidth fairness of TCP flows.
AB  - End-to-end TCP (transmission control protocol) congestion control can cause
      unfairness among multiple TCP connections with different RTT (Round Trip Time).
      The throughput of TCP connection is inversely proportional to its RTT. To resolve
      this problem, researchers have proposed many methods. The existing proposals for
      RTT-aware conditioner work well when congestion level is low. However, they over
      protect long RTT flows and starve short RTT flows when congestion level is high.
      Due to this reason, an improved method based on adaptive thought is proposed.
      According to the congestion level of networks, the mechanism can adaptively
      adjust the degree of the protection to long RTT flows. Extensive simulation
      experiments showed that the proposed mechanism can guarantee the bandwidth
      fairness of TCP flows effectively and outperforms the existing methods.

PMID- 15495329
TI  - A multi-agent system architecture for geographic information gathering.
AB  - World Wide Web (WWW) is a vast repository of information, including a great deal
      of geographic information. But the location and retrieval of geographic
      information will require a significant amount of time and effort. In addition,
      different users usually have different views and interests in the same
      information. To resolve such problems, this paper first proposed a model of
      geographic information gathering based on multi-Agent (MA) architecture. Then
      based on this model, we construct a prototype system with GML (Geography Markup
      Language). This system consists of three tiers-Client, Web Server and Data
      Resource. Finally, we expatiate on the process of Web Server.

PMID- 15495330
TI  - MFV-class: a multi-faceted visualization tool of object classes.
AB  - Classes are key software components in an object-oriented software system. In
      many industrial OO software systems, there are some classes that have complicated
      structure and relationships. So in the processes of software maintenance,
      testing, software reengineering, software reuse and software restructure, it is a
      challenge for software engineers to understand these classes thoroughly. This
      paper proposes a class comprehension model based on constructivist learning
      theory, and implements a software visualization tool (MFV-Class) to help in the
      comprehension of a class. The tool provides multiple views of class to uncover
      manifold facets of class contents. It enables visualizing three object-oriented
      metrics of classes to help users focus on the understanding process. A case study
      was conducted to evaluate our approach and the toolkit.

PMID- 15495331
TI  - Feature selection based on mutual information and redundancy-synergy coefficient.
AB  - Mutual information is an important information measure for feature subset. In
      this paper, a hashing mechanism is proposed to calculate the mutual information
      on the feature subset. Redundancy-synergy coefficient, a novel redundancy and
      synergy measure of features to express the class feature, is defined by mutual
      information. The information maximization rule was applied to derive the
      heuristic feature subset selection method based on mutual information and
      redundancy-synergy coefficient. Our experiment results showed the good
      performance of the new feature selection method.

PMID- 15495332
TI  - An approach to offline handwritten Chinese character recognition based on segment
      evaluation of adaptive duration.
AB  - This paper presents a methodology for off-line handwritten Chinese character
      recognition based on mergence of consecutive segments of adaptive duration. The
      handwritten Chinese character string is partitioned into a sequence of
      consecutive segments, which are combined to implement dissimilarity evaluation
      within a sliding window whose durations are determined adaptively by the
      integration of shapes and context of evaluations. The average stroke width is
      estimated for the handwritten Chinese character string, and a set of candidate
      character segmentation boundaries is found by using the integration of pixel and
      stroke features. The final decisions on segmentation and recognition are made
      under minimal arithmetical mean dissimilarities. Experiments proved that the
      proposed approach of adaptive duration outperforms the method of fixed duration,
      and is very effective for the recognition of overlapped, broken, touched, loosely
      configured Chinese characters.

PMID- 15495333
TI  - Wave propagation of the traffic flow dynamic model based on wavefront expansion.
AB  - This paper discusses propagation of perturbations along traffic flow modeled by a
      modified second-order macroscopic model through the wavefront expansion
      technique. The coefficients in this expansion satisfy a sequence of transport
      equations that can be solved analytically. One of these analytic solutions yields
      information about wavefront shock. Numerical simulations based on a Pade
      approximation of this expansion were done at the end of this paper and results
      showed that propagation of perturbations at traffic flow speed conforms to the
      theoretical analysis results.

PMID- 15495334
TI  - Using Greedy algorithm: DBSCAN revisited II.
AB  - The density-based clustering algorithm presented is different from the classical
      Density-Based Spatial Clustering of Applications with Noise (DBSCAN) (Ester et
      al., 1996), and has the following advantages: first, Greedy algorithm substitutes
      for R(*)-tree (Bechmann et al., 1990) in DBSCAN to index the clustering space so
      that the clustering time cost is decreased to great extent and I/O memory load is
      reduced as well; second, the merging condition to approach to arbitrary-shaped
      clusters is designed carefully so that a single threshold can distinguish
      correctly all clusters in a large spatial dataset though some density-skewed
      clusters live in it. Finally, authors investigate a robotic navigation and test
      two artificial datasets by the proposed algorithm to verify its effectiveness and
      efficiency.

PMID- 15495335
TI  - Nonlinear control for a class of hydraulic servo system.
AB  - The dynamics of hydraulic systems are highly nonlinear and the system may be
      subjected to non-smooth and discontinuous nonlinearities due to directional
      change of valve opening, friction, etc. Aside from the nonlinear nature of
      hydraulic dynamics, hydraulic servo systems also have large extent of model
      uncertainties. To address these challenging issues, a robust state-feedback
      controller is designed by employing backstepping design technique such that the
      system output tracks a given signal arbitrarily well, and all signals in the
      closed-loop system remain bounded. Moreover, a relevant disturbance attenuation
      inequality is satisfied by the closed-loop signals. Compared with previously
      proposed robust controllers, this paper's robust controller based on backstepping
      recursive design method is easier to design, and is more suitable for
      implementation.

PMID- 15495336
TI  - A modified multitarget adaptive array algorithm for wireless CDMA system.
AB  - The paper presents a modified least squares despread respread multitarget
      constant modulus algorithm (LS-DRMTCMA). The cost function of the original
      algorithm was modified by the minimum bit error rate (MBER) criterion. The novel
      algorithm tries to optimize weight vectors by directly minimizing bit error rate
      (BER) of code division multiple access (CDMA) mobile communication system. In
      order to achieve adaptive update of weight vectors, a stochastic gradient
      adaptive algorithm was developed by a kernel density estimator of possibility
      density function based on samples. Simulation results showed that the modified
      algorithm remarkably improves the BER performance, capacity and near-far effect
      resistance of a given CDMA communication system.

PMID- 15495337
TI  - A scalable admission control scheme based on time label.
AB  - Resource reservation protocols allow communicating hosts to reserve resources
      such as bandwidth to offer guaranteed service. However, current resource
      reservation architectures do not scale well for a large number of flows. In this
      paper, we present a simple reservation protocol and a scalable admission control
      algorithm, which can provide QoS guarantees to individual flows without per-flow
      management in the network core. By mapping each flow to a definite time, this
      scheme addresses the problems that limit the effectiveness of current endpoint
      admission control schemes. The overall admission control process is described.
      Analysis is used to explain the reasonability of our scheme and simulation
      validates its performance.

PMID- 15495338
TI  - Genetic programming-based chaotic time series modeling.
AB  - This paper proposes a Genetic Programming-Based Modeling (GPM) algorithm on
      chaotic time series. GP is used here to search for appropriate model structures
      in function space, and the Particle Swarm Optimization (PSO) algorithm is used
      for Nonlinear Parameter Estimation (NPE) of dynamic model structures. In
      addition, GPM integrates the results of Nonlinear Time Series Analysis (NTSA) to
      adjust the parameters and takes them as the criteria of established models.
      Experiments showed the effectiveness of such improvements on chaotic time series
      modeling.

PMID- 15495339
TI  - A hybrid neural network model for consciousness.
AB  - A new framework for consciousness is introduced based upon traditional artificial
      neural network models. This framework reflects explicit connections between two
      parts of the brain: one global working memory and distributed modular cerebral
      networks relating to specific brain functions. Accordingly this framework is
      composed of three layers, physical mnemonic layer and abstract thinking layer,
      which cooperate together through a recognition layer to accomplish information
      storage and cognition using algorithms of how these interactions contribute to
      consciousness: (1) the reception process whereby cerebral subsystems group
      distributed signals into coherent object patterns; (2) the partial recognition
      process whereby patterns from particular subsystems are compared or stored as
      knowledge; and (3) the resonant learning process whereby global workspace stably
      adjusts its structure to adapt to patterns' changes. Using this framework,
      various sorts of human actions can be explained, leading to a general approach
      for analyzing brain functions.

PMID- 15495340
TI  - Hierarchical planning for a surface mounting machine placement.
AB  - For a surface mounting machine (SMM) in printed circuit board (PCB) assembly
      line, there are four problems, e.g. CAD data conversion, nozzle selection, feeder
      assignment and placement sequence determination. A hierarchical planning for them
      to maximize the throughput rate of an SMM is presented here. To minimize set-up
      time, a CAD data conversion system was first applied that could automatically
      generate the data for machine placement from CAD design data files. Then an
      effective nozzle selection approach implemented to minimize the time of nozzle
      changing. And then, to minimize picking time, an algorithm for feeder assignment
      was used to make picking multiple components simultaneously as much as possible.
      Finally, in order to shorten pick-and-place time, a heuristic algorithm was used
      to determine optimal component placement sequence according to the decided feeder
      positions. Experiments were conducted on a four head SMM. The experimental
      results were used to analyse the assembly line performance.

PMID- 15495341
TI  - Automatically extracting sheet-metal features from solid model.
AB  - With the development of modern industry, sheet-metal parts in mass production
      have been widely applied in mechanical, communication, electronics, and light
      industries in recent decades; but the advances in sheet-metal part design and
      manufacturing remain too slow compared with the increasing importance of sheet
      metal parts in modern industry. This paper proposes a method for automatically
      extracting features from an arbitrary solid model of sheet-metal parts; whose
      characteristics are used for classification and graph-based representation of the
      sheet-metal features to extract the features embodied in a sheet-metal part. The
      extracting feature process can be divided for valid checking of the model
      geometry, feature matching, and feature relationship. Since the extracted
      features include abundant geometry and engineering information, they will be
      effective for downstream application such as feature rebuilding and stamping
      process planning.

PMID- 15495342
TI  - Generalized solutions to the Benjamin-Ono equations in sense of Colombeau.
AB  - This paper discusses the existence and uniqueness of the generalized solution in
      the sense of Colombeau to the Benjamin-Ono (B-O) equation and the relationship
      between the new generalized solution and the classical solution.

PMID- 15495343
TI  - Mouse transcriptome: neutral evolution of 'non-coding' complementary DNAs.

PMID- 15495344
TI  - A 48-year-old HIV-positive man with chronic intermittent diarrhea.

PMID- 15495345
TI  - Is intraneuronal amyloid beta-peptide accumulation the trigger of Alzheimer's
      disease pathophysiology?

PMID- 15495346
TI  - Helping teenagers with eating disorders.

PMID- 15495347
TI  - The transformation of child health in the United States.
AB  - Social trends and medical progress have fueled major changes in the epidemiology
      of child health in the United States. Injuries remain a major contributor to
      childhood illness and death. However, among noninjury causes, chronic illness now
      accounts for the majority of children's hospital days and deaths. Although
      mortality rates for all children have fallen dramatically, social disparities
      persist. Approximately half of all excess deaths among African American children
      occur during infancy, primarily from extremely premature births, and the
      remaining portion, primarily from homicide and serious chronic conditions. These
      challenges may require changes in today's child health practices and policies.

PMID- 15495348
TI  - Urinary incontinence.

PMID- 15495349
TI  - Abstracts of the 9th Conference of the International Society for Fracture Repair
      (ISFR). Bologna, Italy, November 2-6, 2004.

PMID- 15495350
TI  - Abstracts of the Anaesthetic Research Society Meeting. Liverpool, United Kingdom,
      July 8-9, 2004.

PMID- 15495352
TI  - Pacemakers for the brain.

PMID- 15495351
TI  - From the electrodiagnostics lab: where transcranial stimulation, H-reflexes and F
      responses monitor cord function intraoperatively.

PMID- 15495353
TI  - Prediabetes--what it is, why it matters.

PMID- 15495354
TI  - The right responses to shoulder pain.

PMID- 15495355
TI  - SSRIs and suicide: how real is the risk?

PMID- 15495356
TI  - I was diagnosed with shingles several months ago, and although the rash has
      healed, I continue to experience pain. How long can this pain persist, is it
      treatable, and is it possible I could have another outbreak of shingles?

PMID- 15495357
TI  - A comparison of in vitro fertilization outcome by culture media used for
      developing cleavage-stage embryos.
AB  - PURPOSE: To determine whether removing glucose and phosphate from media used for
      developing cleavage-stage embryos improves outcome following transfer of fresh or
      frozen embryos. Furthermore the study would evaluate the efficacy of adding
      nonessential amino acids and glutamate to media. METHODS: Embryo development was
      rotated on a weekly basis in human tubal fluid (HTF), versus two media relatively
      devoid of glucose and phosphate (e.g., P1), with one having the addition of
      essential amino acids and glutamate (Quinn's Advantage Medium). RESULTS: For
      fresh cycles, the implantation rate was significantly higher for Quinn's. There
      was less fragmentation with P1 and Quinn's. For frozen cycles, the viable
      pregnancy, implantation rates and embryo quality were higher for Quinn's and P1
      than HTF. CONCLUSION: Removal of glucose and phosphate for day-2 embryos improves
      in vitro fertilization outcome after embryo transfer. It is not clear if adding
      certain non-essential amino acids and glutamate provides further improvement.

PMID- 15495359
TI  - [Animal research trends in the specific production of basic research].

PMID- 15495358
TI  - Outcome of in vitro fertilization-embryo transfer according to age in poor
      responders with elevated baseline serum follicle stimulation hormone using
      minimal or no gonadotropin stimulation.
AB  - PURPOSE: To determine whether decreased ovarian reserve or advancing age are more
      associated with decreased oocyte quality. METHODS: Women with baseline serum
      follicle stimulating hormone (FSH) > 12 mIU/ml who demonstrated previous poor
      response to controlled ovarian hyperstimulation (COH) had oocyte retrieval
      without gonadotropin stimulation in natural cycles or with minimal stimulation
      (maximum 75 IU gonadotropins) without agonists or antagonists were evaluated
      following in vitro fertilization-embryo transfer. RESULTS: The ongoing/delivered
      pregnancy rates were 27.3%, 30.8%, 21.7%, and 0.0%, respectively, with a mean of
      1.06 embryos per transfer. The implantation rates were 33.3%, 28.6%, 14.7%, and
      6.0%. Approximately half of the retrievals resulted in failed fertilization.
      CONCLUSION: Using these minimal or no drug COH regimens in a difficult group of
      women, age was found to be a more adverse infertility factor than elevated serum
      FSH.

PMID- 15495360
TI  - [Animal research statistics in 2003 are slightly smaller--a basis for joy?].

PMID- 15495361
TI  - Evaluation of lateral mechanical tension in thin-film tissue constructs.
AB  - Fibroblast-populated collagen matrices provide a simplified tissue model for
      wound healing and development processes. A technology (CELLDRUM Technology)
      evaluating lateral mechanical tension in fibroblast-populated collagen matrices
      (tissue constructs) with a thickness of 1 mm was introduced. Defined mechanical
      boundary conditions together with the known number and orientation of the cells
      revealed precise data on the average tension exerted by a single cell. Circular
      cell-populated collagen gels were manufactured inside the CELLDRUM on top of a
      flexible membrane. The collagen matrix was then excited by a sound pulse. The
      resulting resonance oscillation was monitored by a laser-based deflection sensor
      and frequency and damping were analyzed giving information on mechanical
      properties of the tissue construct. Several evaluation experiments were
      performed. Calf serum enhanced contractile forces of fibroblasts dose
      dependently. After the gels were treated with cytochalasin D for 24 h, the cell
      forces were reduced by 42% of control. The remaining tension was attributed to
      the extracellular matrix remodeling occurring during cell growth and to other
      cytoskeletal structures like microtubules and intermediate filaments. We also
      found that only after a few hours of culture fibroblast-seeded collagen gels
      began developing significant mechanical tension. A mechanical tension profile of
      proliferating fibroblasts in collagen gels over culture time was obtained.

PMID- 15495362
TI  - Life events, depression and social support in dementia.
AB  - OBJECTIVES: Recent research has highlighted the influence of psychosocial factors
      on the course of dementia, and previous studies have demonstrated an association
      between the experience of life events and depression. This study aimed to
      investigate the interrelationships between life events, depression and social
      support in people with dementia. DESIGN: Participants were 72 people with
      dementia and their carers. Data were collected on severity of dementia, cognitive
      impairment, depression, life events and social support. RESULTS: The results
      showed that 62% of people with dementia who had experienced a severely
      threatening and independent life event in the preceding 3 months were depressed,
      compared with only 28% of those people with dementia without such events (p =
      .005). No relationships were found between social support and depression in
      people with dementia. CONCLUSIONS: This study builds on previous research
      indicating that people with dementia who experience stressful life events have a
      higher risk of depression.

PMID- 15495364
TI  - How long will my column last if I use mobile phases with pH values above 8?

PMID- 15495363
TI  - An unexpected outcome resulting from changes in my gas chromatography system.

PMID- 15495365
TI  - Benefit of clopidogrel over aspirin is amplified in patients with a history of
      ischemic events.

PMID- 15495366
TI  - On location Hampshire. Hard times down south in a tale of two hard-up cities.

PMID- 15495367
TI  - [SOFCEP XVIIth congress report, 26-28 May 2004].

PMID- 15495368
TI  - [Regional differences in health status among 5-6 year-old children as assessed
      from school health screening].

PMID- 15495369
TI  - Expect to see more scrutiny of bariatric surgery.

PMID- 15495370
TI  - When prostate cancer markers become unreliable: the PCPT dilemma.

PMID- 15495371
TI  - Radical cystectomy: the minimally invasive approach.

PMID- 15495372
TI  - Asymptomatic late stent thrombosis after sirolimus stent implantation.

PMID- 15495373
TI  - Bleaching during and after orthodontic treatment.

PMID- 15495374
TI  - Considerations in case acceptance for ABO Phase III examination.

PMID- 15495375
TI  - Substitution treatment for missing lateral incisors.

PMID- 15495376
TI  - Pharmacopoeia of culture media--additional monographs (III).

PMID- 15495377
TI  - [Patient information. Prophylaxis in hepatitis B virus].

PMID- 15495378
TI  - Introduction.

PMID- 15495379
TI  - Death and organ procurement: public beliefs and attitudes.
AB  - Although "brain death" and the dead donor rule--i.e., patients must not be killed
      by organ retrieval--have been clinically and legally accepted in the U.S. as
      prerequisites to organ removal, there is little data about public attitudes and
      beliefs concerning these matters. To examine the public attitudes and beliefs
      about the determination of death and its relationship to organ transplantation,
      1351 Ohio residents >18 years were randomly selected and surveyed using random
      digit dialing (RDD) sample frames. The RDD telephone survey was conducted using
      computer-assisted telephone interviews. The survey instrument was developed from
      information provided by 12 focus groups and a pilot study of the questionnaire.
      Three scenarios based on hypothetical patients were presented: "brain dead," in a
      coma, or in a persistent vegetative state (PVS). Respondents provided personal
      assessments of whether the patient in each scenario was dead and their
      willingness to donate that patient's organs in these circumstances. More than 98
      percent of respondents had heard of the term "brain death," but only one-third
      (33.7%) believed that someone who was "brain dead" was legally dead. The majority
      of respondents (86.2%) identified the "brain dead" patient in the first scenario
      as dead, 57.2 percent identified the patient in a coma as dead (Scenario 2), and
      34.1 percent identified the patient in a PVS as dead (Scenario 3). Nearly one
      third (33.5%) were willing to donate the organs of patients they classified as
      alive for at least one scenario, in seeming violation of the dead donor rule.
      Most respondents were not willing to violate the dead donor rule, although a
      substantial minority was. However, the majority of respondents were unaware,
      misinformed, or held beliefs there were not congruent with current definitions of
      "brain death." This study highlights the need for more public dialogue and
      education about "brain death" and organ donation.

PMID- 15495380
TI  - The Ohio study in light of national data and clinical experience.
AB  - The Siminoff, Burant, and Youngner study in Ohio is strikingly consistent with
      data from a national study. Both suggest that there might be significant public
      acceptance of future policies that violate the dead donor rule, or that further
      extend the boundary between life and death to include brain-damaged patients
      short of "brain death." Experience with donation suggests that many individuals
      would donate their loved ones' organs when they have concluded that the brain
      injury is not survivable, even if all the criteria for "brain death" are not met.
      It would be very helpful to have research on those who have gone through the real
      life clinical situation. Based on the findings of this study and the increasing
      demand for organs, it may be appropriate for public policy to allow for ways to
      increase organ procurement from individuals who are not fully "brain dead" beyond
      the current method of procurement after cardiac death, but any change in this
      area should go slowly and with significant public input.

PMID- 15495381
TI  - Polling and public policy.
AB  - This commentary distinguishes five reasons why one might want to conduct a survey
      concerning people's beliefs about death and the permissibility of harvesting
      organs: (1) simply to learn what people know and want; (2) to determine if
      current law and practice conform to the wishes of the population; (3) to
      determine the level of popular support for or opposition to policy changes; (4)
      to ascertain the causes and effects of popular beliefs and attitudes; and (5) to
      provide guidance in determining which law and practices are ethical. The
      commentary expresses qualms about how well surveys in general can perform with
      respect to the fifth objective, and it provides specific reasons to doubt whether
      this survey is informative from the perspective of a moral philosopher concerned
      with the nature of death and the contours of a permissible system of organ
      procurement.

PMID- 15495382
TI  - Reconsidering the dead donor rule: is it important that organ donors be dead?
AB  - The "dead donor rule" is increasingly under attack for several reasons. First,
      there has long been disagreement about whether there is a correct or coherent
      definition of "death." Second, it has long been clear that the concept and
      ascertainment of "brain death" is medically flawed. Third, the requirement stands
      in the way of improving organ supply by prohibiting organ removal from patients
      who have little to lose--e.g., infants with anencephaly--and from patients who
      ardently want to donate while still alive--e.g., patients in a permanent
      vegetative state. One argument against abandoning the dead donor rule has been
      that the rule is important to the general public. There is now data suggesting
      that this assumption also may be flawed. These findings add additional weight to
      proposals to abandon the dead donor rule so that organ supply can be expanded in
      a way that is consistent with traditional notions of ethics, law, public policy,
      and public opinion.

PMID- 15495383
TI  - [Magnetic resonance imaging of hemangioma of the spleen].

PMID- 15495384
TI  - Leadership through interdisciplinary teams: a case study of an acute pain
      service.
AB  - Interdisciplinary teams are rapidly becoming the standard for the organization
      and delivery of acute care services. Increasingly, research is showing that an
      interdisciplinary approach has the potential to improve patient care.
      Implementing a team approach, however, has challenges because of the various
      perspectives that different disciplines bring. In this paper we present a case
      study of an Acute Pain Service to illustrate how an interdisciplinary team can
      work to improve pain management in hospitals. The development of the Acute Pain
      Service will be described along with a discussion of the challenges that were
      faced. Key lessons will be presented that may lend direction for the
      implementation of an Acute Pain Service or for any other interdisciplinary team.

PMID- 15495385
TI  - RN and RPN decision making across settings.
AB  - Nursing decision making was a focus of the Province-Wide Nursing Project (PWNP),
      a 3-year project to promote best nursing practice. In much of the growing
      literature on nursing decision making, it is assumed that there are differences
      in the way RNs and RPNs make decisions. However, there is little scientific
      evidence to support this assumption. The RN and RPN decision making across
      settings questionnaire was completed by nurses employed in the 23 agencies of the
      4 Participating Complexes taking part in the project. The survey questions were
      subjected to factor analysis and reduced to five factors. Results revealed
      measurable differences between the way that RNs and RPNs made decisions. Both RNs
      and RPNs reported making decisions frequently and experiencing little difficulty
      in making them. However, there were statistically significant differences in the
      frequency with which RNs and RPNs perceived they made decisions and the
      difficulty they found in making them. To plan effective health care, it is
      important to take account of the strengths of different health care workers.
      There is a need for further research to investigate the reasons behind the
      differences revealed in these findings.

PMID- 15495386
TI  - Transition management as an intervention for survivor syndrome.
AB  - In today's health care environment of merged organizations, downsizing and
      restructuring, employees can be experiencing a debilitating syndrome called
      "layoff survivor syndrome." This syndrome can have a crippling effect on workers
      and organizations as employees struggle to adapt to the changed working
      environment. This article represents my self-reflection as a nursing unit manager
      who personally experienced survivor sickness and witnessed its impact on the unit
      staff that I was leading at the time. The work of Noer (1993) is explored to
      clarify the syndrome and describe how the nursing staff and I manifested the
      syndrome. The writings of Bridges (1991), Brockner (1992) and Noer (1993) provide
      timely and relevant insights into managing the impact of layoffs and downsizing
      on those left behind to carry on. Noer (1993) sees the adaptation to the change
      as the ability to make the psychological shift from the old business paradigm
      that perpetuated codependency to the new business paradigm of fostering empowered
      employees. Bridges (1991) takes us a step further in making this psychological
      shift to adapt to the new work environment by providing a three phase process he
      calls transitions. The works of these three authors hold an important message for
      organizations and employees working in environments that abound with constant
      change.

PMID- 15495387
TI  - Profile of a leader: Margaret Mary Hunter CM, CStJ, CD, RN.
AB  - Margaret Mary Hunter (1918-1991) was Chief Nursing Officer for the St.John
      Ambulance Association from 1965-1981. She vigorously promoted the Association's
      Home Nursing course believing every Canadian household should have some one
      trained in home nursing. Her greatest achievement came in 1976 when, at her
      initiative, the Department of National Health and Welfare awarded 1,000,000
      dollars jointly to the Association and the Canadian Red Cross Society to develop
      the multi-media program "There' s No Place Like Home for Health Care".
      Unfortunately this award-winning instructional program was never widely
      implemented and, following her retirement, home health care training in the
      Association declined in importance. Margaret Hunter's efforts to effect change
      illuminate the complex challenges facing nursing leaders of all generations.

PMID- 15495388
TI  - Experiencing nursing governance: developing a post merger nursing committee
      structure.
AB  - In a mid-sized city in south-central Ontario, two hospitals with four physical
      sites underwent a merger to form one large corporation; this merger was in
      response to the recommendations of a provincial restructuring commission. Health
      care delivery within the large corporation was reorganized using a program
      management structure. An outcome of program management within this corporation
      was the dissolution of the traditional nursing departments. In recognition of the
      need for a professional voice, the corporation created a new governance
      structure, which included the Professional Advisory Committee. Twenty-five
      disciplines are represented within this committee; each of these disciplines
      created its own professional committee. Nursing, then, was responsible for
      developing the Nursing Practice Committee (NPC). The following article describes
      the process by which front line nursing staff developed the NPC. A nursing
      structure task force was struck to accomplish this purpose; the task force is
      described, including membership, mandate, activities, principles and goals. The
      environmental assessment that was conducted by the task force is described, along
      with the process by which the NPC structure was designed and implemented.
      Challenges and successes experienced are presented. Rosabeth Kanter's framework
      for staff empowerment is used to understand how nursing governance was
      transformed in the development of the NPC.

PMID- 15495389
TI  - Practice patterns of acute care nurse practitioners.
AB  - This study was undertaken to examine the practice pattern of nurse practitioners
      employed in Ontario acute care settings. A descriptive design, incorporating
      quantitative and qualitative methods for data collection, was used. The acute
      care nurse practitioners' practice pattern varied in terms of scope of practice,
      model guiding practice, reporting relations, and extent of role implementation.
      Role implementation encompassed activities representing the four role components:
      clinical practice, education, administration or management, and research. The
      acute care nurse practitioners engaged most frequently in the clinical component
      of the role. They performed medical and advanced nursing functions. They
      emphasized that they do not work in isolation and that they do not replace
      physicians or residents.

PMID- 15495390
TI  - Implementation of the primary care nurse practitioner role in Ontario.
AB  - The purpose of this descriptive study was to examine the implementation of the
      nurse practitioner role in primary care settings. Nurse practitioners who were
      certified by the College of Nurses of Ontario as Extended Class were surveyed.
      The questionnaire inquired about the nurse practitioners' professional
      characteristics, employment settings, scope of practice, practice pattern, and
      satisfaction with their role. The majority of the 166 respondents working as
      nurse practitioners were Baccalaureate prepared; has been in the role for a
      relatively short period of time; were employed in community health centers; and
      were able to practice to their full potential, within the expanded scope of
      practice. They saw patients who are primarily healthy or presenting with acute
      minor illness, and provided care with an emphasis on wellness. They were
      satisfied with their role. Directions for future research are presented.

PMID- 15495391
TI  - Evaluation of an advanced health assessment course for acute care nurse
      practitioners.
AB  - The Acute Care Nurse Practitioner (ACNP) role is being implemented in many
      centres in Canada. Administrators need to be aware there are very few
      universities in Canada that prepare ACNPs for advanced health assessment.
      Therefore, a need may exist for continuing education in the work environment. The
      ACNPs in London, Ontario recognized such a need, and developed and implemented an
      Advanced Health Assessment Course using available resources, and administrators
      supported participation in the course. A pre-post course evaluation based on
      Bandura's Self-Efficacy theory (1997) was performed. From pre-test to post-test
      there were significant increases in: (a) the use of health assessement skills;
      (b) confidence in performing these skills; and (c) confidence in recognizing
      abnormalities on health assessment. The reasons most often cited for infrequent
      skill use were "inappropriate to clinical setting" and "used only if problem
      suspected". The majority of participants agreed that the course met their needs.
      Implications for practice include administrative support for continuing education
      at other centres to enhance health assessment skills of ACNPs.

PMID- 15495393
TI  - Profile of a leader: pioneer government advisor: Laura Holland, RN, RRC, CBE, LLD
      (1883 - 1956).
AB  - Laura Holland, nurse and social worker, became one of Canada's first official
      "nurse advisors" to government when she was appointed Advisor to the B.C.
      Ministry of Health and Welfare from 1938 to 1945. Before that appointment, she
      had served, with distinction, as a Nursing Sister in World War I, brought
      innovative Red Cross and public health advances to northern Ontario, reformed
      Children's Aid services in Vancouver and B.C., and started a new department that
      combined nursing/social work in the field during the Great Depression of the
      1930s. She was an extraordinary leader.

PMID- 15495392
TI  - Organizational factors influencing nurse practitioners' role implementation in
      acute care settings.
AB  - The purpose of this study was to explore the influence of organizational factors
      on the Acute Care Nurse Practitioner (ACNP) role implementation. A descriptive
      correlational design, incorporating quantitative and qualitative methods for data
      collection was used. The sample of convenience consisted of 57 ACNPs assigned to
      various medical and surgical programs within acute care hospitals. Ten ACNPs
      participated in the unstructured qualitative interviews. In addition to the
      interviews, data pertinent to various organizational factors, including role
      formalization, receptivity of the role by others, perceived autonomy, role
      strain, and additional factors that may interfere with role implementation, were
      collected through a self-report structured questionnaire. A four-diary day was
      completed to gather data on role implementation. Descriptive and correlational
      statistics were used to analyze the quantitative data. The qualitative data were
      content analyzed. The ACNPs engaged most frequently in activities reflective of
      the clinical practice component of the role and less frequently in the non
      clinical components (i.e., education, administration, and research). Results of
      the quantitative and qualitative analyses indicated that lack of formal clear job
      description, conflicting demands and expectations, lack of receptivity of the
      role by others, lack of autonomy, and increased workload were negatively
      correlated with the ACNP role implementation. The ACNP role implementation varies
      across practice settings. This variability should be accounted for when examining
      outcomes of ACNP care.

PMID- 15495394
TI  - Hans Christian Andersen's spelling and syntax: allegations of specific dyslexia
      are unfounded.
AB  - Sources contemporary with Danish author Hans Christian Andersen claimed that he
      did not master the Danish language, which modern studies interpret as specific
      dyslexia. A systematic study of his diaries from age 20 to age 70 found a mean
      spelling error percentage of approximately 1.7 (SD = 1%, range = 0%-4%). A
      methodologically independent reliability study confirmed these figures.
      Andersen's error percentages in poems and letters from ages 11 to 19 show a
      typical initial part of a learning curve that, together with the results from the
      diaries, gives a life span curve of his spelling development. The diaries,
      letters, and poems contain only insignificant syntactic errors. Andersen's
      spelling in the above studies is compared with that of his contemporaries and
      with data from modern studies. His mean error percentages at different ages are
      equal to the figures from nondisabled participants, but between 2 and 15 times
      lower than the mean percentages in studies of individuals with dyslexia. A
      structural analysis of Andersen's spelling errors shows that they are mainly
      phonologically plausible from ages 11 to 70, and that the proportions of
      plausible/implausible errors match those of normal achievers, but not those of
      individuals with dyslexia.

PMID- 15495395
TI  - Inattentive behavior in childhood: epidemiology and implications for development.
AB  - Poor concentration is a relatively common childhood problem. The current North
      American psychiatric diagnostic classification system (Diagnostic and Statistical
      Manual of Mental Disorders, fourth edition; DSM-IV), American Psychological
      Association, 1994) differentiates children whose problems are distinguished
      primarily by symptoms of inattention (ADHD-I) from those whose difficulties are
      characterized by overactive, impulsive behavior by providing various subtypes
      within a broad diagnostic category. Yet, comparatively little is known about
      children who exhibit purely inattentive behavior. This study aims to redress this
      issue by using a large, community-based, epidemiological sample of 7-year-old
      children to compare the developmental functioning, social, and environmental
      backgrounds of children with pure inattentive behavior to that of children with
      pure overactive behavior and combined problems of inattentive and overactive
      behavior. Five hypotheses, centered on the validity of distinguishing inattentive
      behavior from overactivity, are tested. Children with pure inattentive behavior
      were more likely to have general cognitive delays, particularly in the area of
      language development, and were more likely to come from a family in which the
      father was of low occupational status. The results are discussed in relation to
      the implications for research and the identification of needs and intervention
      with children who exhibit pure inattentive behavior.

PMID- 15495396
TI  - Speed of information processing in children referred for learning problems:
      performance on a visual filtering test.
AB  - Children referred for evaluation of learning impairment (LI, N =100) and a
      comparison group of nonreferred (NLI, N = 243) children were evaluated on a
      visual filtering task. The task was designed hierarchically to provide for
      evaluation of component operations-serial search, parallel search, decision, and
      response. With each additional processing demand, response times increased
      disproportionately for the LI group relative to the NLI group. Overall response
      time reliably predicted academic skills and cognitive ability, but was more
      strongly related to group membership. Thus, this nonverbal visual task is
      sensitive to a characteristic of children with learning problems over and above
      discrete academic and cognitive skills. Children with problems adapting to the
      demands of schooling may be distinguished by a disproportionate vulnerability to
      processing load.

PMID- 15495397
TI  - Are working memory deficits in readers with learning disabilities hard to change?
AB  - This study investigated whether changes in the working memory (WM) performance of
      readers with learning disabilities (LD) is related to a general or domain
      specific system. The study compared readers with LD, chronologically age-matched
      (CA-M), and reading level-matched (RL-M) children's WM performance for
      phonological, visual-spatial, and semantic information under initial (no probes
      or cues), gain (cues that bring performance to an asymptotic level), and
      maintenance (asymptotic conditions without cues) conditions. The main findings
      indicated that (a) CA-M children were superior in performance to readers with LD
      across initial, gain, and maintenance conditions, (b) readers with LD showed less
      change (as reflected in effect size scores, slopes for the quadratic curve) on
      both visual-spatial and verbal (phonological and semantic) WM tasks across gain
      and maintenance conditions than the CA-matched children, and (c) the performance
      of readers with LD was superior to the RL-M children's performance on initial
      conditions, but inferior on gain and maintenance conditions. Taken together, the
      results suggest that a general system moderated the changes in retrieval of
      phonological, visual-spatial, and semantic information in readers with LD.

PMID- 15495398
TI  - Mathematical thinking in second-grade children with different forms of LD.
AB  - Based on their performance on a standardized achievement test, second-grade
      children (N = 49) were classified as having mathematics difficulties with normal
      reading achievement (MD only), both mathematics and reading difficulties (MD/RD),
      reading difficulties with normal mathematics achievement (RD only) and normal
      mathematics and reading achievement (NA). Each child was given a series of tasks
      so that we might assess their thinking across four areas of mathematics: number
      facts, story problems, place value, and written calculation. Children with MD/RD
      performed significantly worse than NA children in most areas of mathematical
      thinking, whereas children with MD only performed worse than NA children only on
      complex story problems. The MD-only group outperformed the MD/RD group on story
      problems and written calculation. No significant differences were found between
      the RD-only and NA groups on any of the tasks. The results suggested that among
      children with mathematics difficulties, the MD/RD subgroup is distinct from the
      MD-only subgroup, with the former being characterized by pervasive deficiencies
      in mathematical thinking and the latter by more specific deficits in problem
      solving.

PMID- 15495399
TI  - Effects of tutoring in phonological and early reading skills on students at risk
      for reading disabilities.
AB  - This study examined the effectiveness of nonprofessional tutors in a
      phonologically based reading treatment similar to those in which successful
      reading outcomes have been demonstrated. Participants were 23 first graders at
      risk for learning disability who received intensive one-to-one tutoring from
      noncertified tutors for 30 minutes, 4 days a week, for one school year. Tutoring
      included instruction in phonological skills, letter-sound correspondence,
      explicit decoding, rime analysis, writing, spelling, and reading phonetically
      controlled text. At year end, tutored students significantly outperformed
      untutored control students on measures of reading, spelling, and decoding. Effect
      sizes ranged from .42 to 1.24. Treatment effects diminished at follow-up at the
      end of second grade, although tutored students continued to significantly
      outperform untutored students in decoding and spelling. Findings suggest that
      phonologically based reading instruction for first graders at risk for learning
      disability can be delivered by nonteacher tutors. Our discussion addresses the
      character of reading outcomes associated with tutoring, individual differences in
      response to treatment, and the infrastructure required for nonprofessional
      tutoring programs.

PMID- 15495400
TI  - Effectiveness of a cognitive strategy intervention in improving arithmetic
      computation based on the PASS theory.
AB  - The purpose of this study was to determine if an instruction designed to
      facilitate planning, given by teachers to their class as a group, would have
      differential effects depending on the specific Planning, Attention, Simultaneous,
      Successive (PASS) cognitive characteristics of each child. A cognitive strategy
      instruction that encouraged planning was provided to the group of 19 students
      with learning disabilities and mild mental impairments. All students completed
      math worksheets during 7 baseline and 14 intervention sessions. During the
      intervention phase, students engaged in self-reflection and verbalization of
      strategies about how the arithmetic computation worksheets should be completed.
      The sample was sorted into one experimental and four contrast groups after the
      experiment was completed. There were four groups with a cognitive weakness in
      each PASS scale from the Cognitive Assessment System and one group with no
      cognitive weakness. The results showed that children with a cognitive weakness in
      Planning improved considerably (large effect size of 1.4), in contrast to those
      with a cognitive weakness in Attention (small effect size of 0.3), Simultaneous
      weakness (a slight deterioration and effect size of -0.2), Successive weakness
      (medium effect size of 0.4), and no cognitive weakness (small effect size of .2).
      These data showed that children with a Planning weakness benefitted from the
      instruction designed to help them be more plaful. Those children who received the
      planning-based instruction who were not low inplanning did not show the same
      level of improvement.

PMID- 15495401
TI  - The need for a national nursing strategy.

PMID- 15495402
TI  - Nursing and the Net.
AB  - Web technologies, including intranet and internet applications, have become
      pervasive throughout society. Applications in healthcare settings are evolving
      rapidly and clearly demonstrating that professional and departmental activities
      can be enhanced, streamlined, and supported by this new technology. At Mount
      Sinai Hospital, Toronto, obvious benefits are being derived from evolving
      internet and intranet applications that support nursing practice and management.
      The purpose of this paper is to discuss the advantages of internet/intranet
      functionality for nurses, and to describe an intranet application designed
      specifically for the adult critical care unit.

PMID- 15495403
TI  - A national education strategy to develop nursing informatics competencies.
AB  - Advances in the sophistication of information and communication technologies
      offer nursing practitioners opportunities for better information management, more
      complete documentation of their work, and knowledge development to support
      evidence-based nursing practice. However, a nursing culture that recognizes and
      adopts the contributions of technology to practice is required to take advantage
      of these opportunities. The nature of this change suggests a shift in emphasis
      from specialists in Nursing Informatics (NI) to NI being integrated into all four
      domains of nursing practice. The magnitude of change required on individual,
      organizational and professional levels points to the need for Nursing Informatics
      education strategies on a national level. Recognizing the role and history of NI
      specialists, defining NI and the required NI competencies are necessary first
      steps in developing such a plan. Expanding and adapting the educational
      infrastructure required to support this initiative follows. A working committee
      at the national level with representatives from a number of stakeholder groups is
      currently working on a National Nursing Informatics Project to address these
      issues. This article summarizes key points of an initial discussion paper.

PMID- 15495404
TI  - Pandora's box: physician order entry and nursing work redesign.
AB  - The Canadian health care industry is undergoing unprecedented restructuring in
      response to the quest for quality management and cost reduction. Physician order
      entry and on-line results viewing within a fully integrated hospital clinical
      information system is often thought to be essential to maximum quality
      management, cost control, and clinical decision support. Using Hackman and
      Oldham's Job Characteristics model (1989) as a grounding for discussion, this
      author examines the impact of computerized physician order entry and on-line
      results viewing on the intrinsic meaning of nursing work and its subsequent
      redesign. This paper explores the historical meaning of nursing work related to
      the manual transcription of physician's orders, and contemplates the implications
      for future nursing work and research. Until now there has been little discussion
      in the current informatics literature on this topic.

PMID- 15495405
TI  - Profile of a leader: Rae Chittick: a thoughtful leader.

PMID- 15495406
TI  - What do nurses mean by workload and work overload?
AB  - This paper describes 31 nurses' views of workload and work overload, identifying
      ten dimensions of workload and four dimensions of work overload. Findings suggest
      that researchers and nurse administrators do not include all of the dimensions
      that nurses think of when they use the word "workload". Nurse administrators who
      listen to nurses' experience of workload may be able to find strategies to help
      nurses deal with their workload. The theme of lack of control ran through the
      nurses' accounts of work overload. To retain nurses, employers need to allow
      nurses some control over their workload and some time to include in their nursing
      the things they enjoy the most.

PMID- 15495407
TI  - Liquid chromatography coupled to nuclear magnetic resonance spectroscopy for the
      identification of isoflavone glucoside malonates in T. pratense L. leaves.
AB  - Previous studies revealed that the main isoflavones in extracts of leaves of T.
      pratense L. are biochanin A and formononetin, their 7-O-glucosides, and two
      glucoside malonate isomers of each of them. Since LC-MS(/MS) did not provide
      sufficient information to distinguish the glucoside malonate isomers, in the
      present paper LC-NMR as well as off-line two-dimensional NMR were used to obtain
      further structural information. Matrix solid-phase dispersion (MSPD) was applied
      to obtain sufficiently high analyte concentrations to perform LC-NMR. Stop-flow
      reversed-phase LC-NMR was performed using a gradient of deuterated water and
      deuterated acetonitrile. Offline COSY and NOESY experiments were carried out to
      determine the positions of the glucose moiety on the flavonoid aglycone, and of
      the malonate moiety on the glucose. Based on the fragmentation patterns in MS/MS
      and the NMR spectra, the two formononetin glucoside malonate isomers were
      identified as 7-O-beta-D-glucoside 6"-O-malonate and 7-O-beta-D-glucoside 4"-O
      malonate; i.e. they only differ in the substitution position of the malonate
      group on the glucoside ring. The biochanin A glucoside malonate isomers, however,
      have quite different structures. The main and later eluting isomer is biochanin A
      7-O-beta-D-glucoside 6"-O-malonate, and the minor and earlier eluting isomer is 5
      hydroxy-7-methoxyisoflavone 4'-O-beta-D-glucoside 4"-O-malonate: the positions of
      the methoxy group and the glucoside 6"-O-malonate group on the flavonoid skeleton
      are interchanged.

PMID- 15495408
TI  - Determination of perfluorooctane sulfonate and perfluorooctanoic acid in human
      plasma by large volume injection capillary column switching liquid chromatography
      coupled to electrospray ionization mass spectrometry.
AB  - Rapid, selective, and sensitive methodology for the quantification of
      perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) in human
      plasma using packed capillary liquid chromatography coupled to electrospray
      ionization ion-trap mass spectrometry has been developed. Plasma proteins were
      precipitated using acetonitrile and the resulting supernatant was diluted 1+1
      with water containing 10 mM ammonium acetate (NH4Ac) prior to injection. Sample
      volumes of 250 microL were loaded onto a 30 mm x 0.32 mm ID 10 microm Kromasil
      C18 precolumn by a carrier solution consisting of 10 mM NH4Ac in ACN/H2O (5/95,
      v/v) at a flow rate of 100 microL/min, providing on-line analyte enrichment and
      sample clean-up. Backflushed elution onto a 100 mm x 0.32 mm ID 3.5 microm
      Kromasil C18 analytical column was conducted using an ACN/H2O solvent gradient
      containing 10 mM NH4Ac. In order to improve the robustness and performance of the
      method, perfluoroheptanoic acid (PFHA) was used as internal standard. Separation
      and detection of PFOA, PFHA, and PFOS were achieved within 10 minutes. Ionization
      was performed in the negative mode in the m/z range 250-550. The method was
      validated over the concentration range 1-200 ng/mL for PFOA and over the range 5
      200 ng/mL untreated plasma for PFOS, yielding correlation coefficients of 0.997
      (PFOA) and 0.996 (PFOS), respectively. The within-assay (n = 6) and between-assay
      (n = 6) precisions were in the range 2.1-9.2 and 5.6-12%, respectively. The
      concentration limits of detection (cLOD) of PFOA was 0.5 ng/mL while the cLOD of
      PFOS was estimated to be 0.2 ng/mL in untreated plasma.

PMID- 15495409
TI  - Semipreparative isolation of dehydrodiferulic and dehydrotriferulic acids as
      standard substances from maize bran.
AB  - A method for the isolation of diferulic and triferulic acids in quantities and
      purity that comply with the requirements for their use as standard substances was
      developed. The procedure includes alkaline hydrolysis of destarched maize bran
      and ether extraction of liberated phenolic compounds. Following a first
      purification by liquid-liquid extraction Sephadex LH-20 chromatography is
      performed. This step is the core of the method and allows the separation of
      monomeric and dimeric/trimeric substances. A good pre-separation of di- and
      triferulic acids (purity in most cases >75%) is also achieved. Further separation
      and purification is carried out by semipreparative RP18-HPLC. Using this rapid,
      easy to handle, and moderately priced separation procedure it is possible to
      obtain approx. 41 mg 8-O-4'-diferulic acid, 27 mg 5-5'-diferulic acid, 12 mg 8-5'
      diferulic acid (benzofuran form), 16 mg 8-5'-diferulic acid (open form), 11 mg 8
      5'-diferulic acid (decarboxylated form), 7 mg 8-8'-diferulic acid (cyclic form),
      5 mg 8-8'-diferulic acid (open form), and 10 mg 5-5',8'-O-4"-triferulic acid out
      of 20 g destarched maize bran. The incorporation of minor modifications allows a
      further upscaling of this procedure.

PMID- 15495410
TI  - Retention modelling in liquid chromatographic separation of simvastatin and six
      impurities using a microemulsion as eluent.
AB  - A novel and unique approach was used for retention modelling in the separation of
      simvastatin and six impurities by liquid chromatographic using a microemulsion as
      mobile phase. A microemulsion is a modification of a micellar system where a
      lipophilic organic solvent is dissolved in the micelles; for that reason,
      microemulsions are usually treated as solvent-modified micellar solutions. When
      microemulsions are used as eluents in HPLC separations, solutes partition between
      the charged oil droplets and the aqueous buffer phase. The complexity of the
      composition of the microemulsion permits extensive manipulations to be made
      during method development in order to achieve acceptable resolution of such a
      complex mixture of substances. In order to avoid a laborious "trial and error"
      procedure, a 2(3) full factorial design was applied for choosing an optimal
      microemulsion composition to obtain good separation in a reasonable run time.
      Organic solvent, sodium dodecyl sulphate, and n-butanol content were varied
      within defined experimental domain. Optimal conditions for the separation of
      simvastatin and its six impurities were obtained using an X Terra 50 x 4.6 mm,
      3.5 microm particle size column at 30 degrees C. The mobile phase consisted of
      0.9% w/w of diisopropyl ether, 2.2% w/w of sodium dodecylsulphate (SDS), 7.0% w/w
      of co-surfactant such as n-butanol, and 89.9% w/w of aqueous 25 mM disodium
      phosphate pH 7.0.

PMID- 15495411
TI  - Differences in retention of dioxin-like compounds and organochlorinated
      insecticides on an immunochromatographic column. Interpretation and
      applicability.
AB  - The retention of organochlorinated compounds on an immunochromatographic column
      is studied. The compounds considered are usually found together in real samples
      of environmental concern, and include chlorinated biphenyls, chlorinated dibenzo
      p-dioxins, chlorinated dibenzofurans, and organochlorinated insecticides. The
      different retention observed for different compounds is interpreted in light of
      the structural similarities of the compound studied with that used as a hapten to
      raise the antibodies employed as ligands in the immunochromatographic column.
      Differences in retention of the organochlorinated compounds on the immunocolumn
      make it possible to fractionate them. Mixtures of phosphate buffer solution and
      ACN in different ratios were used as desorption agents. Depending on the
      percentage of ACN employed, different fractionations of the organochlorinated
      compounds are obtained. The use of 20% ACN allows fractionation of most
      insecticides from chlorinated biphenyls, dioxins, and furans. Besides,
      chlorinated biphenyls of different chlorination degree can be separated.
      Moreover, pentachlorinated dioxins and pentachlorinated furans are separated from
      hexachlorinated biphenyls. Fractionation is of critical importance from a
      practical point of view, as it avoids some of the interferences that otherwise
      take place during the subsequent gas chromatography/mass spectrometry (GC/MS)
      analysis of these compounds. In this way, immunochromatography makes it possible
      to perform in a single step all the processes (extraction, clean-up,
      concentration, and fractionation) that are needed prior to the GC/MS analysis of
      these analytes in aqueous samples. An additional advantage of this method is the
      reusability of the immunoaffinity chromatography column for more than 500 times.

PMID- 15495412
TI  - Characterization of sulfated beta-cyclodextrins and determination of enantiomeric
      purity of (1 R,2S)-ephedrine by capillary zone electrophoresis.
AB  - Matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) mass
      spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy were employed
      to characterize two different sulfated beta-cyclodextrins (HS-beta-CD). It was
      found that the HS-beta-CDs have broad heterogeneity in terms of sulfation degree.
      The average sulfate contents were in the range of 6 to 8 per CD molecule.
      Furthermore the sugar moieties of both HS-beta-CDs were sulfated either at
      position 6 or at positions 2 and 6, but not at position 3. Enantiomeric
      separation by capillary zone electrophoresis (CZE) using the HS-beta-CDs as
      chiral selectors showed that these CDs exhibited similar chiral selectivity and
      resolution of the ephedrine enantiomers. One of the CDs was employed for the
      enantiomeric purity evaluation of (1R,2S)-ephedrine (or (-)-ephedrine) by
      capillary zone electrophoresis. Quantification was done by comparison between the
      corrected peak areas of the minor enantiomer and (-)-ephedrine.

PMID- 15495413
TI  - Enantiomer separations on a vancomycin stationary phase and retention mechanism
      of pressurized capillary electrochromatography.
AB  - Several chiral drugs, promethazine, carteolol, celiprolol, and albuterol, were
      resolved with vancomycin as the chiral stationary phase by pressurized capillary
      electrochromatography (pressurized CEC) and capillary HPLC. The effects of
      pressure and electrical field strength on efficiency, resolution, and capacity
      factor in pressurized CEC were investigated. A mathematical model describing the
      relationship of capacity factor in pressurized CEC with voltage, pressurized flow
      velocity, electroosmotic mobility, and electrophoretic mobility was established,
      which was in good agreement with the experimental data.

PMID- 15495414
TI  - Micellar electrokinetic chromatography with laser-induced fluorescence detection
      for rapid and sensitive analysis of two new bioactive reagents using dynamic
      covalent coating.
AB  - A simple, rapid, selective, and sensitive micellar electrokinetic chromatography
      (MEKC) with laser-induced fluorescence detection (LIF) method was developed,
      using hexamethyldisilazane (HMDS) as dynamic covalent coating (DCC), for the
      analysis of two new bioactive agents N-n-hexyl-N'-(sodium p
      aminobenzenesulfonate) thiourea (HXPT) and N-n-undecyl-N'-(sodium p
      aminobenzenesulfonate) thiourea (UPT) derivatized with 4-chloro-7-nitrobenzo-2
      oxa-1,3-diazole. MEKC methods both not using DCC and using DCC were investigated.
      In a series of optimization steps, DCC and a running buffer of 20 mM Na2B4O7 + 16
      mM SDS + 8% acetonitrile were applied for determination of the derivatives.
      Linear relationships for HXPT and UPT were obtained in the range of 5 to 100
      microM (correlation coefficient: 0.9986 for HXPT, 0.9978 for UPT), and the
      detection limits for HXPT and UPT were 16.5 and 39.0 ng mL(-1). The sensitivity
      was improved over that of fluorescence spectroscopy methods. The method was
      applied to the analysis of the two reagents in lab water waste with recoveries in
      the range of 95.6-107.5%.

PMID- 15495415
TI  - Topographical properties of polymer films deposited in capillaries for
      electrophoretic separations of large organic molecules.
AB  - Topography and thickness of hydrophilic polymer coatings of fused-silica
      capillaries for capillary electrophoresis (CE) were investigated using atomic
      force microscopy (AFM), scanning electron microscopy (SEM), and profilometry.
      Three hydrogels, poly(2-hydroxyethyl methacrylate) [poly(HEMA)], poly(diethylene
      glycol monomethacrylate) [poly(DEGMA)], and poly(triethylene glycol
      monomethacrylate) [poly(TEGMA)], were deposited using two procedures, either by
      simple physical sorption of the polymers, or by derivatization of the capillary
      wall surface with glycidyl methacrylate (EPMA) followed by polymerization of the
      appropriate monomers. The performance of the modified capillaries was tested
      under CE conditions (decrease in the electroosmotic flow, EOF dependence on pH,
      separation of milk and standard proteins). It has been found that the most
      important property of the polymer coating is its thickness, whereas its
      topography and the degree of its hydrophobicity are less significant. Film
      deposition by physical adsorption is preferable to polymerization on the
      derivatized surface.

PMID- 15495416
TI  - Optimization of the extraction of paclitaxel from Taxus baccata L. by the use of
      microwave energy.
AB  - A simple and rapid microwave-assisted extraction (MAE) procedure was developed
      and optimized for the extraction of paclitaxel (Taxol) from the needles of yew
      trees Taxus baccata L. grown in Iranian habitats. The samples, immersed in a
      methanol-water mixture, were irradiated with microwaves in a closed-vessel
      system. The method was evaluated using a factorial design approach based on
      parameters such as extraction time, temperature, methanol concentration in water
      (v/v), and the ratio of grams of sample to 10 mL of solvent. Statistical
      treatment of the results revealed that the selected parameters were all
      significant except the extraction time. Optimum conditions would be 1.5 g samples
      in 10 mL solvent (90% methanol), an extraction temperature of 95 degrees C, and
      an extraction time of 7 min. The extracts has been analyzed by reverse-phase high
      performance liquid chromatography with UV detection (LC/UV) at 227 nm for
      quantification. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was
      used for confirmation. The main advantage of the proposed MAE method versus
      conventional solvent extraction (CSE) are the considerable reductions in time (7
      min versus 16 h) and in solvent consumption (20 mL versus 150 mL). The MAE
      procedure yielded extracts that could be analyzed directly without any
      preliminary clean-up or solvent exchange steps. Both extraction methods show RSDs
      lower than 10% and lead to comparable recoveries of paclitaxel (87-92%).

PMID- 15495417
TI  - Beam shaping of focused partially coherent beams by use of the spatial coherence
      effect.
AB  - We demonstrate that when a partially coherent beam with a Gaussian intensity
      distribution is focused by a lens, the desired partially coherent flat-topped
      intensity distribution or doughnut-shaped intensity distribution at the
      geometrical focus can be generated by choice of appropriate form of spectral
      degree of coherence. We provide a novel approach to beam shaping of a partially
      coherent beam and offer new schemes for their potential applications such as
      material processing, optical therapy, and optical tweezers.

PMID- 15495418
TI  - Surface-stabilized ferroelectric liquid-crystal diffraction gratings with
      micrometer-scale pitches.
AB  - The first-order diffraction efficiency eta1 of surface-stabilized ferroelectric
      liquid-crystal (SSFLC) phase gratings is calculated for device thicknesses in the
      range d = 1 to 5 microm and for pitches p of 5 to 20 microm assuming incident
      light at 633 nm. The peak value of eta1 as a function of d has negligible
      dependence on the incoming polarization when p = 20 microm. For smaller pitch
      values the peak value of eta1 decreases and becomes increasingly dependent on the
      orientation of the incoming polarization owing to the influence of the domain
      walls that occur between the SSFLC pixels.

PMID- 15495419
TI  - Rapid optically based measurements of diameter and length for spherical or rod
      shaped bacteria in vivo.
AB  - The application in light scattering of the Mueller matrix ratio (S34)/(S11) for
      determining average particle size is extended to a large size parameter range for
      spherical or randomly oriented rod-shaped particles such as micro-organisms. It
      is shown that combining the graph of this ratio with a Coulter counter
      measurement of particle volume gives results in agreement with microscopic
      measurements. Thus this combination provides a method to measure particle
      diameter and width simultaneously in real time for elongated particles such as
      bacteria, which are measured in vivo with this method. An approximate empirical
      formula is developed to estimate the motion of the extrema in the graph of the
      oscillating matrix ratio as size changes occur. This formula is also shown to be
      consistent with wavelength changes.

PMID- 15495420
TI  - Efficient testing of segmented aspherical mirrors by use of reference plate and
      computer-generated holograms. I. Theory and system optimization.
AB  - Telescopes with large aspherical primary mirrors collect more light and are
      therefore sought after by astronomers. Instead of large mirrors as a single
      piece, they can be made by use of numerous smaller segments. Because the segments
      must fit together to create the effect of a single mirror, segmented optics
      present unique challenges to fabrication and testing that are absent for
      monolithic optics. We have developed a new method for measuring large quantities
      of segments accurately, quickly, and economically using an interferometric test
      plate and computer-generated hologram (CGH). In this test, the aspheric mirror
      segments are interferometrically measured by use of a test plate with a best-fit
      spherical surface. The aspherical departure is accommodated with a small CGH that
      is imaged onto the test plates. The radius of curvature is tightly controlled by
      maintaining the gap between the test plate and the segment. We present a summary
      of the test and give the basic design tradeoffs for using a single system to
      measure all of the segments of a large aspheric mirror.

PMID- 15495421
TI  - Efficient testing of segmented aspherical mirrors by use of a reference plate and
      computer-generated holograms. II. Case study, error analysis, and experimental
      validation.
AB  - Segmented mirrors present unique challenges to fabrication and testing that are
      absent for monolithic optics. Since traditional asphere tests do not address
      segmented optics adequately, we validate a previously developed method to test
      large quantities of segments accurately, quickly, and economically. In this test,
      the aspheric shape of each segment is controlled to high accuracy by use of
      computer-generated holograms, and the radius of curvature is tightly controlled
      by use of the reference plate. In an adjoining paper [Appl Opt 43, 5303 (2004)]
      we developed the theory for this test, and now we present a complete system
      design and optimization for measuring the 1.4-m segments from a 30-m F/1 primary.
      A complete tolerance analysis predicts a test accuracy of 4.8-nm rms surface and
      excellent accuracy for controlling the geometry of the segment. In addition, a
      laboratory demonstration using 30-cm optics is presented that demonstrated 3.9-nm
      rms surface accuracy.

PMID- 15495422
TI  - Design, fabrication, and characterization of high-efficiency extreme-ultraviolet
      diffusers.
AB  - As the development of extreme-ultraviolet (EUV) lithography progresses, interest
      grows in the extension of traditional optical components to the EUV regime.
      Because of the strong absorption of EUV by most materials and because of its
      extremely short wavelength, however, it is difficult to implement many components
      that are commonplace in the longer-wavelength regimes. One such example is the
      diffuser that is often implemented with ordinary ground glass in the visible
      light regime. Here we demonstrate the fabrication of reflective EUV diffusers
      with high efficiency within a controllable bandwidth. Using these techniques, we
      have fabricated diffusers with efficiencies exceeding 10% within a moderate
      angular single-sided bandwidth of approximately 0.06 rad.

PMID- 15495423
TI  - Stroke amplifier for deformable mirrors.
AB  - We demonstrate a simple optical configuration that amplifies the usable stroke of
      a deformable mirror. By arranging for the wavefront to traverse the deformable
      mirror more than once, we correct it more than once. The experimental
      implementation of the idea demonstrates a doubling of 2.0 and 2.04 by two
      different means.

PMID- 15495424
TI  - Green functions for diffuse light in a medium comprising two turbid half-spaces.
AB  - A review of Green functions for diffuse light in two semi-infinite scattering and
      absorbing half-spaces separated by a plane interface is presented. The frequency
      domain Green functions for an intensity-modulated point source are derived within
      the diffusion approximation by the Hankel transform with respect to the variable
      in the plane of the interface. Green functions for a line source and a plane
      source parallel to the interface are obtained from the three-dimensional Green
      functions by the method of descent. Green functions for a steady state are
      obtained as a limit of zero modulation frequency. Connection of the frequency
      domain Green functions with the time-domain Green functions is shown by use of
      the Fourier transform in time. The influence of the relative optical parameters,
      namely, the ratios of diffusion coefficients, absorption coefficients, and
      refractive indices of the two media on the shape of the contour lines of the
      specific intensity, is shown for the continuous and intensity-modulated point
      sources.

PMID- 15495425
TI  - Enhanced birefringence in vacuum evaporated silicon thin films.
AB  - We report an experimental study of enhanced optical birefringence in silicon thin
      films on glass substrates. Form anisotropy is introduced as an atomic-scale
      morphological structure through dynamic control of growth geometry. The resulting
      birefringence is large compared with naturally anisotropic crystals and is
      comparable to two-dimensional photonic crystals. The films are fabricated with
      serial bideposition onto a substrate held at a fixed tilt angle relative to the
      impinging vapor. Films were analyzed by spectroscopic ellipsometry and scanning
      electron microscopy, the latter clearly revealing form anisotropy in a morphology
      of bunched columns perpendicular to the deposition plane with dimensions of
      hundreds of nanometers and smaller. The observed linear birefringence varies with
      wavelength and tilt angle, with a maximum of 0.4 at a 630-nm wavelength and 0.25
      at 1500 nm.

PMID- 15495426
TI  - Linear focusing by a plane grating with curved grooves.
AB  - We study the field diffracted by a plane grating with curved (parabolic) grooves.
      We will demonstrate that when a monochromatic plane wave is incident on a grating
      with parabolic grooves the diffracted field has a focal line whose position
      depends on the curvature radius of the parabolas and the incidence angle of the
      light onto the grating. The effect described has potential applications in
      grating-based devices for focusing light without requiring any additional optics.

PMID- 15495427
TI  - Bayesian neural-networks-based evaluation of binary speckle data.
AB  - We present a new method using Bayesian probability theory and neural networks for
      the evaluation of speckle interference patterns for an automated analysis of
      deformation and erosion measurements. The method is applied to the fringe pattern
      reconstruction of speckle measurements with a Twyman-Green interferometer. Given
      a binary speckle image, the method returns the fringe pattern without noise, thus
      removing the need for smoothing and allowing a straightforward unwrapping
      procedure and determination of the surface shape. Because no parameters have to
      be adjusted, the method is especially suited for continuous and automated
      monitoring of surface changes.

PMID- 15495428
TI  - Analytical method for camera calibration from a single image with four coplanar
      control lines.
AB  - An analytical method to calibrate a camera's extrinsic parameters and effective
      focal lengths is presented. We used a single image with four coplanar control
      lines. Unique solutions of the camera's extrinsic parameters and the two
      effective focal lengths are derived linearly and analytically. If the effective
      focal lengths are known, unique solutions of the extrinsic parameters can be
      derived more easily. Our method can easily be implemented and has better
      precision than the analogous method by use of control points. The results of
      simulated experiments are presented.

PMID- 15495430
TI  - Calculation of Mie derivatives.
AB  - Analytical expressions are found for the derivatives of commonly used Mie
      scattering parameters, in particular the absorption and the scattering
      efficiencies, and for the angular intensity functions. These expressions are
      based on the analytical derivatives of the Mie scattering amplitudes a(n) and
      b(n) with respect to the particle size parameter and complex refractive index. In
      addition, analytical derivatives are found for the volume absorption and
      scattering coefficients, as well as for the intensity functions of a population
      of particles with log normal size distribution. These derivatives are given with
      respect to the total number density, to the median radius and spread of the
      distribution, and to the refractive index. Comparison between analytically and
      numerically computed derivatives showed the analytical version to be 2.5 to 6.5
      times as fast for the single-particle and particle-distribution cases,
      respectively.

PMID- 15495429
TI  - Aerosol lidar intercomparison in the framework of the EARLINET project. 3. Raman
      lidar algorithm for aerosol extinction, backscatter, and lidar ratio.
AB  - An intercomparison of the algorithms used to retrieve aerosol extinction and
      backscatter starting from Raman lidar signals has been performed by 11 groups of
      lidar scientists involved in the European Aerosol Research Lidar Network
      (EARLINET). This intercomparison is part of an extended quality assurance program
      performed on aerosol lidars in the EARLINET. Lidar instruments and aerosol
      backscatter algorithms were tested separately. The Raman lidar algorithms were
      tested by use of synthetic lidar data, simulated at 355, 532, 386, and 607 nm,
      with realistic experimental and atmospheric conditions taken into account. The
      intercomparison demonstrates that the data-handling procedures used by all the
      lidar groups provide satisfactory results. Extinction profiles show mean
      deviations from the correct solution within 10% in the planetary boundary layer
      (PBL), and backscatter profiles, retrieved by use of algorithms based on the
      combined Raman elastic-backscatter lidar technique, show mean deviations from
      solutions within 20% up to 2 km. The intercomparison was also carried out for the
      lidar ratio and produced profiles that show a mean deviation from the solution
      within 20% in the PBL. The mean value of this parameter was also calculated
      within a lofted aerosol layer at higher altitudes that is representative of
      typical layers related to special events such as Saharan dust outbreaks, forest
      fires, and volcanic eruptions. Here deviations were within 15%.

PMID- 15495431
TI  - Three- and four-photon absorption of a multiphoton absorbing fluorescent probe.
AB  - High-order multiphoton excitation processes are becoming a reality for
      fluorescence imaging and phototherapy treatment because they afford minimization
      of scattered light losses and a reduction of unwanted linear absorption in the
      living organism transparency window, making them less susceptible to photodamage,
      while improving the irradiation penetration depth and spatial resolution. We
      report the four-photon-excited fluorescence emission of (7-benzothiazol-2-yl-9,
      didecylfluoren-2-yl)diphenylamine in hexane and its four-photon absorption cross
      section sigma4' = 8.1 x 10(-109) cm8 s3 photon(-3) for the transition S0 --> S1
      when excited at 1600 nm with a tunable optical parametric generator (OPG) pumped
      by picosecond laser pulses. When pumped at 1200 nm, three-photon absorption was
      observed, corresponding to the same transition.

PMID- 15495432
TI  - Characterization of malignant tissue cells by laser-induced breakdown
      spectroscopy.
AB  - Cancer diagnosis and classification is extremely complicated and, for the most
      part, relies on subjective interpretation of biopsy material. Such methods are
      laborious and in some cases might result in different results depending on the
      histopathologist doing the examination. Automated, real-time diagnostic
      procedures would greatly facilitate cancer diagnosis and classification. Laser
      induced breakdown spectroscopy (LIBS) is used for the first time to our knowledge
      to distinguish normal and malignant tumor cells from histological sections. We
      found that the concentration of trace elements in normal and tumor cells was
      significantly different. For comparison, the tissue samples were also analyzed by
      an inductively coupled plasma emission spectroscopy (ICPES) system. The results
      from the LIBS measurement and ICPES analysis were in good agreement.

PMID- 15495433
TI  - Changes in the luminescence between dried and wet bacillus spores.
AB  - Fluorescence has been suggested as a method with which to detect and identify
      bacterial spores. To better understand the nature of the fluorescence signal, we
      observed the intrinsic steady-state fluorescence and phosphorescence spectra of
      Bacillus globigii (BG) in both dried and aqueous forms. In vitro, dried, and
      suspension forms of BG were measured at room temperature in 300-600-nm excitation
      wavelengths. Also, the phosphorescence of dry BG spores was measured at room
      temperature at 300-600-nm excitation wavelengths. The wet BG spores exhibited a
      strong maximum in their fluorescence spectrum, with the peak excitation
      wavelength near 300 nm and emission wavelength near 400 nm. When the BG was
      dried, this peak shifted to an approximately 450-nm excitation maximum and an 500
      nm emission maximum. The difference between the wet and the dry spore
      fluorescence spectra cannot be explained by the phosphorescence of the dry
      spores. Other changes must take place when the spores are wet to account for the
      large changes observed in the spectrum.

PMID- 15495434
TI  - Bariatric surgery: review of common procedures and mortality analysis.
AB  - Obesity is a growing epidemic, and its burden on the health care system and its
      impact on mortality are well known. Bariatric surgery is increasingly used
      worldwide to treat morbid obesity, generally defined as body mass index > or = 40
      kg/m2. Common bariatric surgical procedures are described and mortality analyses
      of two recent clinical studies are presented.

PMID- 15495435
TI  - Screening potential elderly preferred markers: exploratory analysis of
      Cardiovascular Health Study (CHS) data.
AB  - The Cardiovascular Health Study (CHS) analyzes risk factors for coronary heart
      disease and stroke in people age 65 and older. Since CHS is designed to
      comprehensively study cardiovascular risk factors in an elderly population, it
      provides a unique opportunity to study the association of risk factors with
      mortality, as well as morbidity risk. With the growth of the elderly as
      population and life insurance market segments, the need to more precisely
      stratify mortality within a standard risk group of the elderly has grown as well.
      This exploratory analysis assesses medical factors that could be used to improve
      mortality risk stratification within a "standard" mortality population, using the
      CHS public use data set. Participants with a personal history of cardiovascular
      disease, diabetes, or major electrocardiographic abnormalities were excluded from
      the analysis in order to mimic a standard life insurance selection process. Then,
      Cox proportional hazards regression was used to study 10 medical risk factors.
      This model suggested that forced vital capacity >80% predicted, serum creatinine
      <1.5 mg/dL (133 mcmol/L), hemoglobin >11 g/dL (110 g/L), and serum albumin >3.5
      mg/L (35 mmol/ L) are significantly associated (p = 0.05) with favorable
      mortality. C-reactive protein <1 mg/L is associated with favorable mortality at
      borderline significance levels (p = 0.09). On the other hand, a family history of
      cardiovascular disease (MI and/or stroke) and low BMI (<26 kg/m2) are associated
      with unfavorable mortality in the analysis. Total to HDL cholesterol ratio of <6,
      presence of supine systolic blood pressure < or = 140 mmHg, and the presence of
      minor rest electrocardiographic findings were not statistically significant
      factors in the multivariate model. Further assessment of the predictive value of
      the "significant" medical factors identified is required in insured lives.

PMID- 15495436
TI  - Mortality in rheumatoid disease.
AB  - This paper provides an overview of rheumatoid disease from the perspective of its
      impact on mortality. The term, rheumatoid arthritis, may promote the
      misconception that this disease is relatively trivial and easily managed;
      therefore, "rheumatoid disease" is preferred. Numerous long-term studies in many
      settings have established that significant excess mortality is associated with
      rheumatoid disease, and that this excess mortality is related to cardiovascular
      disease deaths. Inflammation in rheumatoid and cardiovascular diseases shares the
      same biologic mechanisms. Severity of extraarticular disease, decline in
      functional level, and level of inflammatory activity are associated with
      increased risk of mortality. Detection and measurement of novel inflammatory
      biomarkers may provide tools to assess prognosis and to monitor therapy. Close
      attention to the management of traditional cardiovascular risk factors is
      essential in these patients. Whether disease modifying antirheumatic drug (DMARD)
      therapy will reduce all-cause and cardiovascular disease mortality in rheumatoid
      disease is the subject of ongoing studies.

PMID- 15495437
TI  - Dementia screening using computerized tests.
AB  - The preclinical phase of dementia usually precedes the clinical diagnosis by many
      years. Early detection of dementing conditions during this preclinical phase may
      provide opportunities for treatments that may slow or mitigate progression.
      Conventional assessment tools usually can only detect dementia when the symptoms
      are overt and the disease is well-established. Computerized neurocognitive
      screening tools hold promise for diagnosing dementia in its early phase. The use,
      performance and development of several computerized screening tools to diagnose
      and monitor patients with pre-dementias and dementia are reviewed. The ability to
      accurately assess the presence of dementia clearly has direct relevance to
      insurance risk assessment and risk management. As new treatments appear, their
      role in clinical management of dementia patients will increase as well. In a
      future issue, the differential diagnosis of dementias related to the findings on
      these screening tools will be reviewed.

PMID- 15495438
TI  - Conversion of mortality ratios to a numerical rating classification for life
      insurance underwriting-revisited.
AB  - This is a commentary requested by the J Insur Med Editor to accompany a
      reprinting in this 2004 issue of my 1988 article on "Conversion of Mortality
      Ratios to a Numerical Rating Classification for Life Underwriting" (J Insur Med
      1988;20:54-61). Topics discussed in this commentary include the distinction
      between short-term and long-term mortality follow-up in certain conditions, the
      format and the introductory text of the US Decennial Life Tables, the distinction
      between mortality rate and mortality probability, averaging mortality rates over
      a period of years, and the great value of the exemplary follow-up study used in
      the 1988 article.

PMID- 15495439
TI  - Conversion of mortality ratios to a numerical rating classification for life
      insurance underwriting. 1988.

PMID- 15495440
TI  - Prostate cancer: a review of common underwriting problems, Part 1.
AB  - Part 1 of a two-part discussion of Prostate Cancer from an underwriting
      perspective, covers the epidemiology and screening for prostate cancer. Included
      is a "Primer on Screening Tests" that discusses problems with digital rectal exam
      (DRE) and prostate specific antigen (PSA) as screening tests. Approaches to
      enhancing the use of PSA for screening including age and race specific ranging,
      PSA density, PSA velocity, free PSA, and complexed PSA are discussed. Arguments
      for and against the use of PSA for prostate cancer are presented. The widespread
      use of PSA testing in the insurance setting is contrasted with cautious
      statements concerning general use of PSA in the clinical preventive care setting.
      In a future issue, Part 2 will cover staging and follow-up of treated prostate
      cancer.

PMID- 15495441
TI  - Tall R wave in lead V1.
AB  - Tall R waves in lead V1 present the life insurance company medical director with
      a diagnostic dilemma. This ECG pattern may be present in applicants with right
      bundle branch block, right ventricular hypertrophy, Wolff-Parkinson-White
      syndrome, posterior myocardial infarction, hypertrophic cardiomyopathy, muscular
      dystrophy, dextrocardia, misplaced precordial leads, as well as in normal
      individuals. This ECG case study discusses the ECG features involved in the
      differential diagnosis.

PMID- 15495442
TI  - Proteinuria as a mortality risk.
AB  - This case report examines the factors involved in the mortality risk of low-grade
      proteinuria. Proteinuria and microalbuminuria are defined and the use of the
      protein-creatinine ratio is discussed. Studies from the medical literature
      suggest that albuminuria complements risk selection in diabetics and nondiabetics
      and may parallel or adversely modify other cardiovascular risk factors.

PMID- 15495443
TI  - Pemphigus.
AB  - Pemphigus vulgaris and the related pemphigus vegetans, pemphigus foliaceus and
      pemphigus erythematous, are associated with the highest mortality among primary
      skin diseases. Typical findings are illustrated.

PMID- 15495444
TI  - Renal cell carcinoma--serendipitous scanning.

PMID- 15495445
TI  - Patient fears: overcoming dentistry's public perception.

PMID- 15495446
TI  - Global rumblings, dentistry style. Israel's dental dilemma, a fluoride crisis in
      Australia, and Thailand's attempt to save its national symbol (via root canal).

PMID- 15495447
TI  - How home care is essential to ensuring successful orthodontic treatment outcomes.
AB  - Patients can significantly affect the outcome of their orthodontic treatment. A
      practice committed to developing the right systems, scripts, and educational
      materials will experience a more satisfied patient, increased efficiencies, and
      higher profits. Educating and motivating patients to maintain their oral health
      and providing recommendations or dispensing of home care tools such as a power
      toothbrush increases patient compliance, positively impacts treatment outcomes,
      enhances customer service, and generates a new revenue stream for the practice.
      In a tight economy and a highly competitive orthodontic market, a power
      toothbrush can positively impact your marketing and case close rate. Treatment
      and fees being relatively equal, patients will tend to accept treatment from a
      practice that can demonstrate concern for the patients' overall oral health and
      greater value-added components to the orthodontic case. Power toothbrushes as
      part of a comprehensive orthodontic treatment provide a great differentiating
      marketing strategy.

PMID- 15495448
TI  - The role of the infection control coordinator.

PMID- 15495449
TI  - Solving the problems of maxillary asymmetry and the gummy smile.

PMID- 15495450
TI  - Using the golden proportion in aesthetic treatment: a case report.
AB  - Many dental patients are unhappy with their smile but believe a beautiful smile
      is outside their budget. The first step is to listen to the patient in order to
      understand what his or her primary concerns are. The second step is to examine
      carefully and analyze the case to develop a treatment plan that will fulfill as
      much as possible of the patient's desires within the context of his or her
      constraints (financial or otherwise). Also, remember that dentistry doesn't end
      when the last veneer is placed or the last bill is paid. The final step is to
      maintain a strong relationship with your patients to ensure good oral hygiene and
      restorations that are as long-lasting as they are beautiful.

PMID- 15495451
TI  - Full-arch fixed prosthetics supported by dental implants and natural teeth:
      planning, provisionalization, treatment sequences: 2 case examples.

PMID- 15495452
TI  - Do traditional sealants have a place in the new, super-magnified world?
AB  - The original concept of dental sealants is truly intoxicating... that an entry
      level auxiliary could prevent occlusal caries by painting over the grooves of the
      teeth, thereby freeing up the doctor for more difficult tasks... all with a tidy
      profit. The realities of high-level magnification and research are sobering the
      "sealant euphoria." Today, we now understand that prevention of occlusal caries
      is significantly more complex and technically challenging than originally
      thought. Changing the process from a lower-skill, auxiliary-driven procedure to a
      high-skill, microscope-centered procedure will require a shift in scheduling and
      value systems. Earlier in the article I mentioned my nephew with the catastrophic
      sealant failures. Today he drives 4 hours to the airport and then flies another 2
      hours so that he can receive a microscope-centered level of care (and pays in
      full). Microscope-enhanced dentistry is much more than simply making tiny little
      holes in teeth. It is a commitment to dentistry where vision is uncompromised,
      and today that level can best be attained with an operating microscope.

PMID- 15495453
TI  - Access to success, part 3: Super-efficient anterior root canals.

PMID- 15495454
TI  - Microendodontic ultrasonic instruments.

PMID- 15495455
TI  - The clinical use of night guards: occlusal objectives.

PMID- 15495456
TI  - Everyday uses of adult orthodontics.
AB  - Adults are now much more in favor of receiving orthodontic treatment than in the
      past. The baby boomer generation has a deep desire to keep their "youngness" and
      is willing to invest in such. Along with this attitude has come the ability to
      treat malocclusions and other clinical deficiencies with new products that
      decrease the treatment time. Nickel titanium wire has revolutionized the
      mechanics of treatment, so that often only one wire need be used throughout
      treatment, and the time of care has been reduced. Invisalign has resulted in
      higher acceptance rates for treatment that was passed up before. Although
      Invisalign has its limitations, for most basic alignment, it can provide a nice
      result. Patients who might come to an office for Invisalign can be open to braces
      if Invisalign will not correct their problem. In this article, several uses of
      adult orthodontics have been shown. It behooves the general practitioner to refer
      those cases that can benefit from the multiple uses of orthodontics. Should the
      GP desire to learn to perform any or all of the tooth movements necessary to
      create a more desired outcome, there are several marketed orthodontic courses
      that will provide the knowledge necessary. Finally, I encourage those who would
      enjoy treating patients with orthodontic needs. I have found it to be very
      rewarding to work toward a shared outcome that is often a less invasive
      treatment. Patients really enjoy the results.

PMID- 15495457
TI  - Infection of dental implements and appliances, part 1: The toothbrush.

PMID- 15495458
TI  - NCRP report No. 145: New dental X-ray guidelines: their potential impact on your
      dental practice.

PMID- 15495459
TI  - Saliva, chewing gum, and oral health.

PMID- 15495460
TI  - How bad ads can undermine good practices: get your message in print properly and
      new patients will follow.

PMID- 15495461
TI  - The eleven essentials of effective staff meetings, part 2: Getting it together in
      the name of customer service.
AB  - So there you have them: our first 5 Essentials: (1) Punctuality; (2) No
      Interruptions; (3) No Titles, No Privileges; (4) No Hanging Back, No
      Monopolizing; and (5) A Written Agenda. Meetings, even the best intentioned of
      them, need structure, and we are confident that if you adopt these rules, or some
      reasonable facsimile, you will see great improvement in both staff and patient
      relationships. In my next article, the remaining 6 Essentials will be discussed,
      including how we put the Essentials to effective use.

PMID- 15495462
TI  - Do you know the score? Using statistics to win the game of dental practice.

PMID- 15495463
TI  - [Urinary calculi].

PMID- 15495464
TI  - [Urinary calculi epidemiology in children].
AB  - We identified 40 pediatric patients with urolithiasis. There were 27 boys and 13
      girls. Initial symptoms were abdominal pain, with or without microscopic
      hematuria in 40% of the cases, and urinary tract infection/pyelonephritis in 25%
      of the cases. Stones were made of struvite (35% of the cases), calcium-phosphate
      (25%) or calcium-oxalate (20%). The high prevalence of struvite stones reflects
      the importance of urinary tract infection a major cause of urolithiasis in that
      specific age group. Hypercalciuria was the most common urinary biochemical
      abnormality, found in more than 50% of the children. In the absence of a
      spontaneous passage of the stone, extra-corporeal shock wave lithotripsy
      represents an excellent therapeutic option. This article emphasizes the
      importance of stone analysis and extensive biochemical investigations in children
      with urolithiasis, in order to avoid recurrence and potential progression towards
      chronic renal failure.

PMID- 15495465
TI  - [Lithogenesis].

PMID- 15495466
TI  - [Analysis and classification of calculi: contribution to the etiology of
      calculous disease].

PMID- 15495467
TI  - [Value of the study of crystalluria in clinical practice].

PMID- 15495468
TI  - [Medical treatment of urinary lithiasis].
AB  - Urinary stone disease is frequent, and characterized by a high recurrence rate.
      Prevention of recurrent urolithiasis is possible using an appropriate diet with
      or without medications. Patients should be encouraged to have a high fluid
      intake. For an adult, urine volume should exceed 2000 ml/day. Diet modification
      should be done according to the various metabolic factors contributing to the
      formation of the stone (ie, hypercalciuria, hyperoxaluria, hypocitraturia,
      hyperuricuria, and so forth). Calcium intake should be around 1000 mg/day,
      protein intake limited to 1.2 g/kg/day, and salt intake kept to less than 100-150
      mEq/jour. For uric acid urolithiasis, patient should limit uric acid intake to
      less than 500 mg/day. If these dietary manoeuvers fail, one can use thiazide
      diuretics to treat hypercalciuria, potassium citrate to correct hypocitraturia or
      sodium bicarbonate to alkalanize urine and prevent uric acid stone formation.

PMID- 15495469
TI  - [Infective lithiasis].
AB  - We report the case of a 69-year-old woman, with a BMI of 42.9, suffering from
      bilateral struvite calculi and who raised end stage renal failure. Urease
      synthesizing bacteria, leading to the hydrolysis of urea into ammonium and to an
      alkaline urine (pH > 7.2), are required for struvite stone formation in humans.
      Struvite component constitutes the majority of staghom calculi. Patients with
      struvite stones could lose renal function because of obstructive or
      pyelonephritic episodes and surgical interventions on the kidney. Therapeutic
      success needs a follow up by a specialized uro-nephrologist team as soon as
      possible.

PMID- 15495470
TI  - [Cysteine lithiasis].
AB  - Cystinuria is a common inherited amino-aciduria resulting in abnormal urinary
      excretion of cystine and the dibasic aminoacids, lysine, arginine and ornithine.
      Formation of cystine kidney stones, recurrent infections and subsequent renal
      failure are the main complications of the disease. Recently, the gene SLC3A1 and
      SLC7A9, encoding the two subunits rBAT et b0,+AT of the proximal renal
      transporter complex, have been identified. In this article, we report the medical
      history of a 30-year-old patient and discuss the recent molecular progress, the
      clinical evolution, and the medical treatment of the cystinuria.

PMID- 15495471
TI  - [Massive hyperoxaluria].
AB  - Primary hyperoxaluria type I is a rare inborn error of metabolism caused by a
      deficiency of a liver-specific peroxisomal enzyme. It manifests by increased
      oxalate production that ultimately results in kidney failure, due to urolithiasis
      and nephrocalcinosis, and finally induces systemic oxalosis and risk of premature
      death. Primary hyperoxaluria type 2 is mainly responsible of urolithiasis.
      Enteric hyperoxaluria is a commonly seen adverse event of Crohn disease or after
      extensive intestinal resection. These affections represent the main etiologies of
      massive hyperoxaluria. If not recognized very soon and adequately treated, these
      conditions can progress rapidly to end stage renal failure.

PMID- 15495472
TI  - [Drug-induced lithiasis].

PMID- 15495473
TI  - [Radiologic and biochemical studies of urinary lithiasis].
AB  - Clinical investigations of a patient with urolithiasis include a careful history
      and radiological and biochemical evaluation. Stone analysis by infrared
      spectrophotometry remains the most important step. These investigations are
      essential in order to understand why a patient developed urolithiasis and, most
      importantly, how to avoid its recurrence in the future. Simple exams are often
      enough in a patient with a single urolithiasis episode. But biochemical
      evaluation should be extensive in a child, or an adult with several urolithiasis
      episodes or with renal insufficiency.

PMID- 15495474
TI  - [Urologic treatment of lithiasis].
AB  - The urological treatment of urolithiasis has completely changed during the last
      20 years with a huge technical development. Many eclectic fields as aeronautical,
      micromechanic, Laser and optical research as well as computerised radiology have
      contributed to this evolution. We discuss here, the several therapeutic
      modalities, with there applications, combinations and various indications.

PMID- 15495476
TI  - [Diagnosis and management of kidney diseases in children].

PMID- 15495475
TI  - [6th French Swisse Conference of Practical Pediatrics organized by the French
      Swisse Task Force on Ambulatory Pediatrics (GREPA)].

PMID- 15495477
TI  - [Therapeutic implications of early screening of deafness].

PMID- 15495478
TI  - [Screening of vision disorders in young children].
AB  - Twenty pediatricians conducted a study for the detection of ophtalmological
      defects in children aged 36 to 54 months using a protocol designed by the Groupe
      Romand d'Etudes en Pediatrie Ambulatoire (GREPA) and by an ophthalmologist. After
      a pilot test run for correcting the protocol and the testing procedure, visual
      acuity was assessed using the Scholatest, stereoscopy using the Lang test and
      ocular deviation using the Hirschberg test. A total number of 1243 children were
      examined, some of which needed to be tested twice. The visual acuity assessment
      provided an abnormal result in 241/1387 tests (17.4%); stereoscopy defects were
      detected in 39/1371 tests (2.8%) and strabismus in 41/1446 tests (5.7%). The test
      system allowed for detection of ophtalmological abnormalities in 14.7% of all
      children. This first Swiss study on detection of ophtalmological defects in
      preschool age children has established the feasibility of the testing procedure
      in ambulatory pediatrics during a routine examination. This procedure allows
      earlier detection of defects as well as earlier treatment with a better outcome.
      Early detection of ophtalmological defects has obvious Public Health
      implications.

PMID- 15495479
TI  - [Gastroenterologic problems in children].

PMID- 15495480
TI  - [The knee in children and adolescents].

PMID- 15495481
TI  - Measuring professional values: authors respond.

PMID- 15495484
TI  - Cultural incommensurability.

PMID- 15495486
TI  - The KwaZulu-Natal health promotion model.
AB  - PURPOSE: To describe a health promotion model aimed at assisting primary health
      care nurses to incorporate health promotion into their practice. ORGANIZING
      STRUCTURE: The model is based on empowering people through a systematic, planned,
      needs-driven curriculum with comprehensive content, using interactive teaching in
      small groups, and linking the groups with external resources. The process
      involves identifying and engaging partners, planning the project, implementing
      it, and then disengaging. METHODS: The implementation of this model in a province
      of South Africa, KwaZulu-Natal, in a collaborative project involving two
      universities and the state health services, changed the practice of the primary
      health care nurses involved. They worked with women's groups over 3 years and
      changed both their own perspectives and the lives of the women. CONCLUSIONS:
      Unless nurses have an implementation model available to them, they frequently
      focus only on illness needs of people and do not participate in health promotion.

PMID- 15495487
TI  - Symptom clusters in oncology patients and implications for symptom research in
      people with primary brain tumors.
AB  - PURPOSE: To provide a critical analysis of the state of the science of research
      on symptom clusters in the general oncology population, compared to symptom
      research in the primary brain tumor population. ORGANIZING CONSTRUCT: Symptoms
      are a multidimensional experience that include perceptions of the frequency,
      intensity, distress, and meaning as symptoms occur and are expressed. A symptom
      can influence the occurrence and meaning of other symptoms. METHODS: Literature
      pertaining to symptom presentation in people with primary brain tumors and the
      occurrence of multiple symptoms and symptom clusters in patients with cancer was
      reviewed and analyzed. FINDINGS: Symptoms occur in clusters in general oncology
      patients, and these clusters have been shown to influence functional status. The
      potential effect of tumor biology on symptom clusters is shown by the cluster of
      symptoms theorized to be associated with proinflammatory cytokine production. In
      patients with primary brain tumors, few researchers have examined the occurrence
      of symptoms at the time of diagnosis. Studies to date are retrospective and
      descriptive and were conducted before the use of modern imaging techniques.
      Studies of symptom clusters have not been reported for patients with primary
      brain tumors. CONCLUSIONS: Symptom clusters have recently been identified in the
      general oncology population and might provide a new strategy for assessment and
      intervention. Neurologic symptoms in patients with primary brain tumors are those
      related to increased intracranial pressure and those that are location-dependent
      within the brain. Therefore, application of the symptom cluster paradigm to guide
      research is warranted.

PMID- 15495488
TI  - Quality of life in women with breast cancer in Turkey.
AB  - PURPOSE: To determine quality of life (QoL) of Turkish women with breast cancer,
      and to examine whether QoL was related to sociodemographic or clinical variables.
      DESIGN: This descriptive study was conducted with a convenience sample of 72
      Turkish women with breast cancer recruited from two hospitals in Turkey. METHODS:
      The data were collected using a questionnaire, the Quality of Life Scale (QoLS),
      and the Visual Analogue Scale (VAS), and were analyzed using descriptive
      statistics. FINDINGS: Two sociodemographic variables (educational background and
      employment status) were related to QoL of women with breast cancer. No
      statistically significant difference was found between patients with and without
      pain on scores obtained from the overall QoLS. CONCLUSIONS: The mean scores of
      total scale and subscales related to QoL perceived by women were considered to be
      moderately high. However, findings showed that educational level, employment
      status, and level of pain affected the level of QoL in Turkish women with breast
      cancer in varying degrees. Further studies are needed to determine specific
      effects of sociodemographic and clinical variables on QoL.

PMID- 15495489
TI  - Testing the efficacy of a creative-arts intervention with family caregivers of
      patients with cancer.
AB  - PURPOSE: To test the efficacy of a creative arts intervention (CAI) with family
      caregivers of patients with cancer. DESIGN: A pre-posttest quasi-experimental
      design, with participation in the CAI as the independent variable and stress,
      anxiety, and emotions as the dependent variables. METHOD: The 6-month study was
      implemented at a regional cancer treatment center with family caregivers. The CAI
      consisted of several creative arts activities designed for delivery at the
      bedside. FINDINGS: Forty family caregivers reported significantly reduced stress,
      lowered anxiety, and increased positive emotions following CAI participation.
      CONCLUSIONS: The CAI promoted short-term well being in this family caregiver
      sample. Caregivers also increased positive communication with cancer patients and
      health care providers while expressing delight over their handmade pieces of art.

PMID- 15495490
TI  - Evidence-based practice and research utilization activities among rural nurses.
AB  - PURPOSE: To identify the extent to which rural nurses utilize evidence-based
      practice guidelines from scientific research in their practice; to describe both
      previous and current research utilization activities in which they have
      participated, and to identify the specific barriers they face in their practice
      settings. DESIGN AND METHODS: Data for this descriptive study were collected
      through questionnaires with open-ended questions focused on (a) current
      utilization of nursing research findings, (b) previous involvement in nursing
      research activities, and (c) participation in medical research activities. The
      participants were 106 nurses from various practice areas in six rural counties of
      a southwestern state in the United States. FINDINGS: Results revealed that only
      20.8% of the participants stated they were currently involved in research
      utilization, and they were mostly nurses with bachelor's degrees. The two most
      common areas of current research utilization were pain management and pressure
      ulcer prevention and management. Barriers to research utilization, such as rural
      isolation and lack of nursing research consultants, were identified. CONCLUSIONS:
      The types of research utilization activities identified by these nurses indicate
      how much the facilities in which these nurses work in the rural areas are
      striving with the utilization of available scientific evidence. Rural nurses face
      unique barriers related to situational and geographic factors, with implications
      for nursing administrators, researchers, and educators.

PMID- 15495491
TI  - Becoming a mother versus maternal role attainment.
AB  - PURPOSE: To present evidence for replacing the term maternal role attainment
      (MRA), with becoming a mother (BAM). METHODS: A review of the evolution of MRA
      and a synthesis of research emanating from the theory was done, followed by
      synthesis of current research on the transition to motherhood. FINDINGS: A woman
      establishes maternal identity as she becomes a mother through her commitment to
      and involvement in defining her new self. Maternal identity continues to evolve
      as the mother acquires new skills to regain her confidence in self as new
      challenges arise. CONCLUSIONS: BAM more accurately encompasses the dynamic
      transformation and evolution of a woman's persona than does MRA, and the term MRA
      should be discontinued.

PMID- 15495492
TI  - Role strain and ease in decision-making to withdraw or withhold life support for
      elderly relatives.
AB  - PURPOSE: To describe the concepts of role strain and role satisfaction (renamed
      ease in decision-making following analysis) experienced by family caregivers when
      making decisions to withdraw or withhold life support for elderly relatives in a
      variety of settings. METHODS: Semi-structured interviews were conducted with 17
      family caregivers to obtain descriptions of their experiences when making
      decisions about life support for elderly relatives. Content analysis was used to
      analyze the data. FINDINGS: Role strain was complex, dynamic, and
      multidimensional, and it evolved over time before, during, and after decision
      making about life support. Role satisfaction, the concept name used at the
      beginning of the study, did not match descriptions or the experience of family
      caregivers, and a revised name, ease in decision-making, was selected.
      CONCLUSIONS: The concepts of role strain and ease in decision-making have not
      previously been used in studies of decisions about life support. Both role strain
      and ease in decision-making augment the existing literature on role strain in
      family care by providing a more complete picture of caregivers' responses during
      their experience of making life-support decisions. Research focused on the
      measurement of strain and ease in decision-making is needed to understand their
      interrelationship as well as their association with such variables as caregiver
      grief and health.

PMID- 15495493
TI  - The cross-cultural relationships between nurses and Filipino Canadian patients.
AB  - PURPOSE: To describe culturally embedded values that implicitly guide Filipino
      Canadian patients' interactions with Canadian nurses and are integral to nurse
      patient relationships. DESIGN AND METHODS: A focused ethnography was conducted,
      with a purposive sample of 23 Filipino-Canadians who received care in Canadian
      hospitals. Data consisted of interviews, field notes, and diary. FINDINGS: When
      receiving care, patients delineated hindi ibang tao (one of us) and ibang tao
      (not one of us) and this determined their preference for who performed personal
      and private tasks or received information. The urgency of the patients'
      conditions, the intimacy required for most nursing procedures, and short
      hospitalizations meant that patients often interacted without progressing through
      the cultural levels of pakikitungo (formality), pakikibagay (adjustability), and
      pakikisama (acceptance). Rather, the crisis of being hospitalized forced patients
      to immediately move toward the cultural levels of pakikipagpalagayang-loob
      (mutual comfort) or pakikiisa (oneness). Patients' willingness to trust and to
      share their kapwa-oriented worldview in relating with fellow human beings, and
      their use of their languages of words, gaze, touch, and food, allowed nurses to
      become hindi ibang tao (one of us). Caregiving roles and establishing
      relationships also distinguished that hindi ibang tao (one of us) was to bantay
      (watch over) the patient, whereas ibang tao (not one of us) was expected to alaga
      (care for) them (i.e., provide professional care). CONCLUSIONS: Communicating and
      caring effectively requires understanding of Filipino Canadians' languages of
      words, gaze, touch, and food and their levels of interaction. Culturally safe
      nurse-patient relationships can then develop.

PMID- 15495494
TI  - A comparison of three measures of elder abuse.
AB  - PURPOSE: To present a comparison of three measures for assessing elder abuse.
      DESIGN AND METHODS: Three measures for assessing elder abuse were identified
      through a literature review. The characteristics and uses of each measure were
      reviewed and evaluated. FINDINGS: The Indicators of Abuse (IOA) is a 22-item tool
      for discriminating abuse and nonabuse cases; it is completed by a health care
      professional after a home assessment is conducted. The Elder Abuse and Neglect
      Assessment (EAI) is a 44-item scale comprised of seven sections to review signs,
      symptoms, and subjective complaints of elder abuse, neglect, exploitation, and
      abandonment; it can be used by health care providers in all clinical settings.
      The Elder Abuse Screening Test (EAST) is a 15-item tool to be completed by a
      health care provider based on the patient's responses. This screening tool is
      limited because of the small unrepresentative samples used to test it, the low
      internal consistency, and a relatively high false-negative rate. CONCLUSIONS: An
      instrument to accurately assess elder abuse in long-term care is needed. Proper
      identification of elder abuse is the first step in assisting victims in dealing
      with abusive situations.

PMID- 15495495
TI  - Content validity and nursing sensitivity of community-level outcomes from the
      Nursing Outcomes Classification (NOC).
AB  - PURPOSE: To evaluate the content validity and nursing sensitivity of six
      community-level outcomes from the Nursing Outcomes Classification (NOC; Johnson,
      Maas, & Moorhead, 2000). DESIGN AND METHODS: A survey research design was used.
      Questionnaires were mailed to 300 public health nursing experts; 102 nurses
      responded. Experts evaluated between 11 and 30 indicators for each of the six
      outcomes for: (a) importance of the indicators for measuring the outcome, and (b)
      influence of nursing on the indicators. Content validity and nursing sensitivity
      of the outcomes were estimated with a modified Fehring technique. FINDINGS: All
      outcomes were deemed important; only Community Competence had an outcome content
      validity score < .80. The outcome sensitivity score for Community Health:
      Immunity was .80; other outcome scores ranged from .62-.70. Indicator ratios for
      all 102 indicators met the study criterion for importance, with 87% designated as
      critical and 13% as supplemental. Sensitivity ratios reflected judgments that 45%
      of the indicators were sensitive to nursing intervention. CONCLUSIONS: The study
      provided evidence of outcome content validity and nursing sensitivity of the
      study outcomes; further validation research is recommended, followed by testing
      of the study outcomes in clinical practice. Community-level nursing-sensitive
      outcomes will potentially enable study of the efficacy and effectiveness of
      public health interventions focused on improving health of populations and
      communities.

PMID- 15495496
TI  - A survey of IRB process in 68 U.S. hospitals.
AB  - PURPOSE: To compare IRB processes in 68 U.S. hospitals for the same multicenter
      study. DESIGN: Survey of IRB processes in 68 U.S. hospitals during 2001-2002.
      METHODS: Requirements of IRB submission including type and duration of review and
      qualifications of principal investigator were compared by hospital bed size,
      region, and academic affiliation. FINDINGS: The majority of hospitals (63.2%)
      were on the East coast, and mean bed size was 465 (range: 77-2,112). About one
      third (33.8%) required that the principal investigator listed on the application
      be from within the institution, 26.5% required evidence of human subjects
      research training, 10.3% required a conflict of interest statement. Mean number
      of pages for the application was 5.24 (1-31) and up to eight copies were
      requested. Time from submission of the IRB application to approval averaged 45.4
      days (range, 1-303 days), and the majority of reviews were "expedited" (61.8%).
      Expedited reviews required more time (mean, 54.8 days) than did either exempt
      (mean, 10.8 days) or full (mean, 47.1 days) reviews. CONCLUSIONS: Current IRB
      review processes are cumbersome and nonstandardized, and review time varies
      widely. The absence of efficient and streamlined review might unnecessarily
      impede national clinical research projects without improving participant safety.

PMID- 15495497
TI  - Working with human research protections.
AB  - PURPOSE: To provide a primer for novice nurse scientists about the increasingly
      regulated human research environment. ORGANIZING CONSTRUCTS: Federal regulations
      and international guidelines about protection of human research participants are
      discussed, with particular attention to institutional review boards for human
      research. CONCLUSION: Understanding the processes used by institutional review
      boards to foster ethical human research promotes collaborative interactions and
      supports compliant research work.

PMID- 15495498
TI  - A dimensional analysis of role enactment of acute care nurses.
AB  - PURPOSE: To identify dimensions of the role enactment process of acute care
      nurses. DESIGN: Dimensional analysis, rooted in grounded theory methodology, was
      used to analyze the role enactment process. METHODS: Twenty-eight articles
      related to acute care staff nurse roles were selected for analysis. Articles were
      from eight countries and were published between 1995 and 2002. Significant
      phrases or themes from each document were categorized to identify themes.
      FINDINGS: Initial analysis of the articles indicated 37 separate dimensions in
      the role enactment process of acute care nurses. The final, integrative analysis
      reduced the initial 37 to 7 core dimensions: care delivery, autonomy, culture
      management, information management, leadership, psychologic management, and
      relationship management. The analysis showed a role that is rooted in management
      processes. CONCLUSIONS: The multidimensional nature of the role of acute care
      nurses was indicated in the dimensional analysis. The findings have implications
      for the administration and education of nurses, as well as for human resource
      development of nurses in many parts of the world.

PMID- 15495499
TI  - Development and psychometric evaluation of the Professional Practice Environment
      (PPE) scale.
AB  - PURPOSE: To describe the Professional Practice Environment (PPE) scale, its
      conceptual development and psychometric evaluation, and its uses in measuring
      eight characteristics of the professional practice environment in an acute care
      setting. DESIGN AND METHODS: The 38-item PPE Scale was validated on a sample of
      849 professional practice staff at the Massachusetts General Hospital in Boston.
      Psychometric analysis included: item analysis, principal components analysis
      (PCA) with varimax rotation and Kaiser normalization, and internal consistency
      reliability using Cronbach's alpha coefficient. FINDINGS: Eight components were
      shown, confirming the original conceptually derived model's structure and
      accounting for 61% of explained variance. Cronbach's alpha coefficients for the
      eight PPE subscales ranged from .78 to .88. CONCLUSIONS: Findings showed the 38
      item PPE Scale was reliable and valid for use in health outcomes research to
      examine the professional practice environment of staff working in acute care
      settings.

PMID- 15495500
TI  - [The routine oral examination in The Netherlands. An orientation from the
      perspective of general dental practitioners].
AB  - In The Netherlands the routine oral examination (ROE) can be characterized as an
      important tool in dental care. As a result of the changing prevalence of oral
      diseases of the Dutch population the content of the routine oral examination has
      changed over time. A representative survey among general dental practitioners has
      been carried out to investigate the professional performance in the routine oral
      examination. Participants consisted of a random, stratified sample of 619
      dentists, of whom 521 (85%) responded. The Dutch general dental practitioners use
      the routine oral examination mainly for detecting dental caries and to asses the
      status of the restorations. About 50% of the responders use a standard recall
      interval for all patients whereas the other half takes individual patient factors
      into consideration when determining the recall interval. Both groups differ
      significantly on the variables: 'time spend on the routine oral examination',
      'the amount of diagnostic activities', 'the registration in patient dental
      records' and 'the frequency of using bitewing radiographs'. In the perspective of
      quality of dental care a national reconsideration of the routine oral examination
      by professionals and patients is advocated. The instrument of choice would be the
      use of evidence-based clinical practice guideline development procedures.

PMID- 15495501
TI  - [ART or conventional restorations? A final evaluation of proximal restorations in
      deciduous molars].
AB  - In this article the success rate of class 2 ART and conventional (prepared with a
      bur) restorations in deciduous molars is described. In 1999 approximately 200 ART
      and 200 conventional restorations were made in deciduous molars in Bandung,
      Indonesia. The restorations were evaluated after 1.5 month, half a year, 1 year,
      2 years and 3 years. The three-year evaluation took place in October 2003.
      Results show that after 3 years 31% (ART) and 33.6% (conventional) of the
      restorations were successful (no significant difference). There was a significant
      difference between the operators. If keeping the element until shedding is the
      only criterion, the success rate increased to 53.

PMID- 15495502
TI  - [Restoration of oral functions following a (partial) mandibulectomy due to an
      oral carcinoma].
AB  - For patients diagnosed with malignant oral lesions invading the mandible, a
      partial or complete mandibulectomy is unavoidable. In predicting the invasion of
      the lesion, preoperative imaging techniques are used, such as an
      orthopantomogram, computed tomography, and magnetic resonance imaging. A
      mandibular discontinuity can be restored using a stainless steel or titanium
      reconstruction plate, or using autogenous non-vascularized or vascularized bone
      grafts. In achieving the goal of complete rehabilitation endosseous permucosal
      implants can be inserted in order to support a prosthesis. There is a tendency of
      a higher implant loss frequency among bone-grafted patients who have had implants
      after irradiation when compared with non-irradiated patients. After a (partial)
      mandibulectomy, oromandibular reconstruction by non-vascularized or vascularized
      bone grafts and endosseous implants provides a unique opportunity to restore some
      oral functions.

PMID- 15495503
TI  - [Research methods in dentistry 3. Material analysis in the framework of the
      diagnosis of toxic and allergic reactions].
AB  - In dentistry studies concerning systemic effects of dental materials are scarce.
      However, in vitro research showed that from each metal-containing restoration
      ions will be released. These metal ions can be spread locally but also in the
      entire human body and initiate an immune response. Nickel and palladium are
      recognized as the most allergenic elements. In this manuscript a method for
      evaluation of the alloy composition is described which may help dentists to
      reveal the relation between alloy compostion and health effects.

PMID- 15495504
TI  - [An unnecessary endodontic treatment and extraction due to defective diagnosis].
AB  - A 22-year-old male patient was referred by his dentist to a department of Oral
      and Maxillofacial Surgery because of recurrent swelling of the oral mucosa of
      unknown origin in region 17. One year before, molar 17, although clinically sound
      but showing an apical radiolucency, was endodontically treated. Eight months ago,
      molar 17 was removed because of recurrent complaints. Clinical examination
      revealed a fistula with purulent drainage in region 17. Radiographic examination
      revealed the cause, viz. a follicular cyst originating from the right wisdom
      tooth located in the maxillary sinus. Thus, the persisting complaints in region
      17 were not related to molar 17, but related to a chronically inflamed follicular
      cyst originating from an impacted third molar.

PMID- 15495505
TI  - [Teeth decoration back after a long and forgotten history].
AB  - After the last ice-age modern man started to remove, file, dye and inlay teeth.
      The teeth had such a central role in the imagination that the habit of more or
      less ritual decoration by incurable manipulation of the teeth spread all over the
      world. The most skillful and artistic work was done by craftsmen of the Maya.
      Between 1500 and 1900 modern researchers classified the habits as primitive and
      barbarian but during the twentieth century some of them took the question
      seriously. In the last decennium tooth jewelery is sold more and more often. In
      two articles the history of teeth decoration is outlined. In this article the
      significance of the manipulations is emphasized. The second will focus on the
      changing appreciation of the phenomenon.

PMID- 15495506
TI  - [Neuroleptic malignant syndrome in users of risperidone].
AB  - Neuroleptic malignant syndrome is a potentially life-threatening complication of
      neuroleptic therapy. Three nursing-home residents who suffered from multiple
      somatic disorders and dementia, two men aged 78 and 76 years respectively and a
      woman aged 72 years, developed neuroleptic malignant syndrome following the use
      of risperidone. The first two patients presented with severe muscular pain.
      Initially, none of them exhibited high fever and so it is debatable whether the
      diagnosis 'neuroleptic malignant syndrome' can be excluded in the absence of
      fever. A review of the literature indicates that the syndrome can easily be
      mistaken for an infection. Patients with extrapyramidal side effects as a result
      of earlier use of neuroleptics seem to be more vulnerable to developing
      neuroleptic malignant syndrome. Patients using neuroleptics who become ill with
      an altered level of consciousness, sweating and muscular rigidity, should at
      least have their blood tested for the level of creatine phosphokinase activity.
      Furthermore, pain might be an initial symptom. Treatment of the neuroleptic
      malignant syndrome failed in all three patients, and they died.

PMID- 15495507
TI  - [Sentinel node metastasis in the case of colorectal cancer. No role for sentinel
      node biopsy at present].
AB  - With sufficient experience, sentinel node biopsy has a high identification rate
      for several techniques in the case of colorectal cancer. However, the sensitivity
      of the procedure seems to be too low to justify the replacement of routine
      pathological examination of the whole mesentery by sentinel node biopsy.
      Unexpected lymphatic drainage patterns can be found in about 5% of the patients.
      Therefore, the role of sentinel node biopsy in determining the extension of the
      resection is minimal in the case of colorectal cancer. In contrast, sentinel node
      biopsy is helpful in identifying the lymph nodes with the highest risk of
      harbouring metastases and it facilitates the scrutinising of the lymph node by
      the pathologist. This will lead to more micrometastases being detected. The
      prognostic significance of micrometastases and the impact on survival of adjuvant
      systemic therapy in such patients should be investigated in randomised controlled
      trials. At present, sentinel node biopsy in colorectal cancer should be
      restricted to a research setting.

PMID- 15495508
TI  - [Cardiac rehabilitation in patients with a congenital heart disease, an
      implantable cardioverter defibrillator or chronic heart failure].
AB  - Cardiac rehabilitation is no longer just used to treat patients after the
      manifestation of a coronary artery disease such as a myocardial infarct, after a
      PTCA or after a coronary bypass operation. Patients with a congenital heart
      disease, patients who have received an implantable cardioverter defibrillator
      (ICD) and patients with stable chronic heart failure are also suitable candidates
      for a multidisciplinary cardiac rehabilitation programme. The new Dutch
      guidelines for cardiac rehabilitation, published in 2004, can be helpful in
      identifying potential candidates for a programme. Physical training is often a
      component of the treatment, but psycho-social counselling and education targeted
      at reducing anxiety and uncertainty, accepting the heart disease and learning to
      cope with it, can be just as important as those aspects targeted at improving the
      physical condition. Cardiac rehabilitation that includes physical training is
      safe for patients with congenital heart disease, for patients who have undergone
      an ICD implantation and for patients with stable chronic heart failure, as long
      as the pretraining exercise test is given a guiding role in selecting the
      appropriate physical work load. Patients with stable chronic heart failure should
      continue their physical training in order to maintain its beneficial physical and
      psychological effects.

PMID- 15495509
TI  - [Protection of children born to hepatitis-B-infected mothers].
AB  - The vaccination schedule implemented on 1 March 2003 for the approximately 1000
      Dutch children per year born to hepatitis-B-virus-infected mothers is under
      discussion. The Health Council of The Netherlands and TNO have both published
      reports which reveal that the current schedule does not fulfil its objectives, as
      too many children are completely missed and many of the vaccinated children do
      not receive their scheduled vaccinations on time. Furthermore, doubts have been
      expressed about the effectiveness of the present vaccination schedule. In line
      with one of the schedules proposed by the Health Council we suggest the
      introduction of a 4-dose vaccination, in which the first vaccination is given
      immediately after the birth of the child. The subsequent vaccinations can then
      take place after 2, 4 and 11 months. These are the ages at which other children
      are also vaccinated against hepatitis B in accordance with the Dutch national
      vaccination programme. Furthermore, we advise an improved surveillance to ensure
      compliance with the individual vaccination schedules for these children. If data
      from the hepatitis-B screening of pregnant women, the regional vaccination
      registers, and the vaccinations actually administered are linked, then it will be
      possible to take swift action if a child is late for a hepatitis-B vaccination.
      In our opinion, this can best be achieved if a single national organisation is
      made responsible for the entire process, starting from the collection of the
      hepatitis-B data of pregnant women up to concluding the scheme, whether or not
      the serologic response is checked.

PMID- 15495510
TI  - [Diagnostic image (206). A woman with dyspnoea and retrosternal pain after
      vaginal delivery].
AB  - A 27-year-old healthy woman suffered from dyspnoea and retrosternal pain after a
      spontaneous vaginal delivery due to a pneumomediastinum and subcutaneous
      emphysema caused by labour.

PMID- 15495511
TI  - [Increased risk of hepatitis B due to incomplete or untimely immunisation in one
      quarter of infants of hepatitis-B-virus carriers].
AB  - OBJECTIVE: To determine the frequency of an increased risk of infection in
      children of hepatitis-B-virus carriers due to incomplete or untimely hepatitis-B
      immunisation. DESIGN: Descriptive. METHOD: Dates of birth and hepatitis-B
      immunisations were collected for all documented children of hepatitis-B-virus
      carriers in the vaccination registers, born in 2000 in The Netherlands. To assess
      the possible increased risk of infection, criteria were drawn up for the
      completeness and timeliness of the immunisations and on the basis of these the
      number of children who possibly had an increased risk of infection was
      determined. RESULTS: In total, 731 of the 769 children (95%) had received
      hepatitis-B immunoglobulins and at least 3 vaccinations. For 200 children (26%)
      the deviation from the immunisation schedule was so great that the child was
      possibly (temporarily) inadequately protected. CONCLUSION: A quarter of the
      children of hepatitis-B-virus carriers were immunised incompletely or at the
      wrong time. This calls for an adjustment of the immunisation schedule and
      national guidelines in which the responsibilities and tasks are clearly defined.

PMID- 15495512
TI  - [The incidence and initial symptoms of diabetes mellitus type 1 in 0-14-year-olds
      in the Netherlands, 1996-1999].
AB  - OBJECTIVE: To determine the incidence and characteristics of type-1 diabetes
      mellitus (DM) in children aged 0-14 years during the period 1996-1999 and to
      compare this with previous measurements of the incidence. DESIGN: Descriptive.
      METHOD: Data were collected via reports from all practicing paediatricians to the
      Dutch Paediatric Surveillance Unit and a questionnaire among members of the Dutch
      Diabetes Association. The incidence was calculated by the capture-recapture
      method, and the characteristics and symptoms of the children were determined from
      the questionnaires. RESULTS: The incidence of DM type 1 among 0-14-year-olds
      increased to 18.6/100,000/year (95% CI: 17.7-19.4) compared to 11.1/100,000/year
      (10.5-11.7) in 1978-1980. The increase was highest in the youngest age group, 0-4
      years. DM type 1 was diagnosed at an average age of 7.6 years (7.4-7.9) and in
      1988-1990 at 9.2 years (9.0-9.5). The boy-girl ratio also increased. Children
      with a mother from Surinam, Turkey or The Netherlands Antilles had lower risk of
      DM type 1 while a higher risk was calculated for children from Moroccan and
      Somali mothers. In comparison with 1993-1994, there were less frequent lethargy
      or dehydration; lower average serum-glucose values, a better blood pH and less
      frequent ketonuria at the time of diagnosis. Treatment on an outpatient basis had
      increased. However, over the time span 1993-1999, Moroccan children (n = 108)
      showed dehydration, ketonuria and low blood-pH values more frequently than
      children of Dutch parents (n = 1825) and their hospital admission lasted longer.
      CONCLUSION: The incidence of DM type 1 had increased and the disease manifested
      itself at a younger age. The clinical condition at time of diagnosis, however,
      was better. The incidence and clinical characteristics differed between children
      of different ethnic origin.

PMID- 15495513
TI  - [Outbreak of amoebiasis in a Dutch family; tropics unexpectedly nearby].
AB  - An amoebic liver abscess, amoebic dysentery and asymptomatic cyst passage were
      diagnosed in a father, a mother and one of their three children, respectively.
      One of the other children had been in the tropics, but only after the father's
      symptoms had begun. All three family members were infected with the same strain
      of Entamoeba histolytica as determined by polymerase chain reaction (PCR)-based
      DNA typing. The source of infection was most probably in Southern Italy where the
      family regularly spent their summer holidays. All three infected patients
      recovered after drug treatment. In a patient with a liver abscess or colitis,
      amoebiasis should be considered even in the absence of a history of a stay in the
      tropics. Stool samples should be examined for amoebic cysts and trophozoites. PCR
      analysis of parasite DNA extracted directly from stool samples makes
      differentiation between the morphologically identical cysts of E. histolytica and
      the non-pathogenic Entamoeba dispar possible. In addition, serum antibodies to E.
      histolytica are almost always present in symptomatic patients. Invasive
      infections with E. histolytica require treatment with a tissue amoebicidal drug,
      followed by a contact amoebicide to prevent recurrence. Currently, paromomycin is
      considered to be the first-line luminal amoebicide because of its efficacy and
      safety.

PMID- 15495514
TI  - [Surgery and follow-up 131I therapy in patients with differentiated thyroid
      carcinoma in the south-east of the Netherlands, 1983-1996, compliance with the
      1987 consensus guidelines: additional data].
AB  - In a previous study using data from the regional cancer registry of the
      Comprehensive Cancer Centre South, Eindhoven, The Netherlands, we concluded that
      in the majority of cases surgical treatment was in accordance with the consensus
      recommendations, but that about 40% of patients with differentiated thyroid
      cancer from a number of regional hospitals had not been referred for 131I
      therapy. However, in a subsequent study using patient data from these hospitals,
      it became clear that almost all patients had in fact been referred for therapy
      but to centres outside the 131I therapy region. The conclusion of the study
      should therefore be altered: the great majority of patients with differentiated
      thyroid cancer in the south-east of The Netherlands (1983-96) were referred for
      131I treatment and therefore the primary surgical and the follow-up treatment
      complied with the 1987 consensus guidelines.

PMID- 15495515
TI  - [The practice guideline 'Dementia' (second revision) from the Dutch College of
      General Practitioners].

PMID- 15495516
TI  - ['Hyperventilation syndrome': often an easy-to-treat panic disorder].

PMID- 15495517
TI  - [Diagnostic image (193). A man with a palpable swelling in the upper abdomen].

PMID- 15495518
TI  - [On the Scientific School].

PMID- 15495519
TI  - [Topography of changes in EEG spectrum power during a session of biological
      feedback of the beta rhythm].

PMID- 15495520
TI  - [Positron emission tomography of the human brain in relation to psychological
      defense mechanisms in patients with multiple sclerosis].

PMID- 15495521
TI  - [Specificity of hemispheric asymmetry in prosody perception in schizophrenia and
      in the norm].

PMID- 15495522
TI  - [Interhemispheric relationships in opiate-addicted patients during the withdrawal
      and early post-withdrawal periods].

PMID- 15495523
TI  - [Effect of various depressive states on the emotional evaluation of short musical
      fragments in humans].

PMID- 15495524
TI  - [Features of autonomic regulation and the character of convulsions in stammering
      children].

PMID- 15495525
TI  - [Effect of microcirculation reserves on spinal cord recovery after traumatic
      injury].

PMID- 15495526
TI  - [Dependence of heart weight on body weight in patients with cardiovascular
      diseases].

PMID- 15495527
TI  - [The role of the metabolic status of the donor and the recipient in survival of a
      skin graft according to histological data].

PMID- 15495528
TI  - [Hormonal regulation of lipid metabolism in healthy subjects and in patients with
      obesity].

PMID- 15495529
TI  - [Physiological mechanisms of histamine-induced hyposensibilization in infectious
      allergic bronchial asthma].

PMID- 15495530
TI  - [Postural effects on the hormone level in healthy subjects. Communication I. The
      cobra posture and steroid hormones].

PMID- 15495531
TI  - [Characteristics of central hemodynamics in women with different body mass living
      in the European North].

PMID- 15495532
TI  - The effects of estrogen on indices of skeletal muscle tissue damage after
      eccentric exercise in postmenopausal women.
AB  - This study examined if estrogen (E) usage (in the form of hormone replacement
      therapy [HRT]) has a protective effect on skeletal muscle damage in
      postmenopausal women. Nine postmenopausal women (age 55.2 +/- 9.9 [mean +/- SD])
      performed two exercise sessions at 70% of their maximal heart rate on HRT (E-HI)
      and without HRT (E-LO; following a 28-45 day HRT washout). All subjects followed
      a condition order of E-HI then E-LO with at least 42 days between exercise
      sessions. Serum creatine kinase (CK), perceived delayed onset muscle soreness
      (DOMS), and maximal quadriceps isometric force (MIF) were taken pre-exercise, 24,
      48 and 72-hr post exercise. E-HI and E-LO conditions produced a rise in CK (p <
      0.001) after exercise; but CK after E-HI was greater than in E-LO (p < 0.001) at
      24 hours and at 48 hours. DOMS was significantly elevated at 24, 48, and 72-hr
      post each exercise session (p < 0.05). The greatest peak DOMS score occurred
      during the E-HI condition. MIF was similarly reduced after each exercise session
      (p < 0.05). These results suggest elevated E does not offer a protective effect
      to skeletal muscle; however, design limitations (i.e., condition order) confound
      the present data. Interestingly, an association between peak-CK during the E-LO
      condition and the number of washout days (r = +0.707, p < 0.05) between
      conditions existed. This suggests a longer washout period may be necessary to
      elucidate the actual E effects on skeletal muscle. These findings suggest that
      more work correcting for the present design limitations is warranted on this
      topic.

PMID- 15495533
TI  - [Physiological criteria of endurance in athletes].

PMID- 15495534
TI  - [The role of monoarticular and biarticular muscles of the lower limb in ground
      locomotion].

PMID- 15495535
TI  - [Free fatty acids and Ca2+ in blood plasma of endurance-trained athletes after
      prolonged physical exercise].

PMID- 15495536
TI  - [Relationships between thyroid hormones, blood rheology, and lipid profile in
      athletes].

PMID- 15495537
TI  - [Functional status of the locomotor system in young children according to turn
      amplitude analysis of the electromyogram].

PMID- 15495538
TI  - [Correlation between electrophoretic mobility of erythrocytes and erythrocyte
      count in blood].

PMID- 15495539
TI  - [Alveolar bone regeneration stimulated by a combination of platelet-rich plasma
      and Cerasorb graft in Beagle dogs. Histological and histomorphometric studies].
AB  - Healing of extraction wounds was examined in an animal experiment model on Beagle
      dogs. After bilateral extraction of the premolars of 12 dogs the alveoli were
      filled up with a combination of beta-tricalcium phosphate (Cerasorb) graft and
      platelet rich plasma (PRP) on the experimental side, and with Cerasorb alone on
      the control side. Biopsy specimens were taken from the regenerating bone at 6, 12
      and 24 weeks after surgery for histological study. Results of the histologic and
      histomorphometric examinations revealed that after 6 weeks the newly formed bone
      was significantly denser on the experimental side. After 12 weeks this difference
      became moderate, and after 24 weeks the bone forming activity was nearly equal on
      the two sides. These results suggest that local administration of Cerasorb and
      PRP results in more intense bone regeneration, especially in the early phase.

PMID- 15495540
TI  - [Periodontal abscess: etiology, diagnosis and treatment].
AB  - The periodontal abscess is an acute destructive process in the periodontium
      resulting in localized collections of pus communicating with the oral cavity
      through the gingival sulcus or other periodontal sites and not arising from the
      tooth pulp. The prevalence of periodontal abscess is relatively high and it
      affects the prognosis of the tooth. Periodontal abscesses can develop on the base
      of persisting periodontitis but can also occur in the absence of periodontitis.
      The cause of the development of periodontal abscess originating from chronic
      periodontitis is the marginal closure of a periodontal pocket, or the pocket
      lumen might be too tight to drain the increased suppuration due to changes in the
      composition of subgingival microflora, alteration of bacterial virulence or host
      defenses. Diagnosis of a periodontal abscess is based on medical and dental
      history as well as oral examination (pocket depth, swelling, suppuration,
      mobility, sensibility of the tooth). The most prevalent group of bacteria: P.
      gingivalis, P. intermedia, B. forsythus, F. nucleatum and P. micros. Previous
      studies have suggested that the complete therapy of the periodontitis patients
      with acute periodontal abscess has to do in two stages: the first stage is the
      management of acute lesions, then the second stage is the appropriate
      comprehensive treatment of the original and/or residual lesions. The management
      of acute lesions includes establishing drainage via pocket lumen, subgingival
      scaling and root planing, curettage of the lining pocket epithelia and seriously
      inflamed connective tissue, compressing pocket wall to underlying tooth and
      periodontal support, and maintaining tissue contact. Some authors recommend the
      incision or to establish drainage and irrigation, or a flap surgery, or even
      extraction of hopeless teeth. We recommend the use of systemic antibiotics as a
      preventive measure of systemic disease or in case of systemic symptoms.

PMID- 15495541
TI  - [Prosthetic treatment of patient with multiple sclerosis (MS) and intact
      masticatory function (case report)].
AB  - Comprehensive dental care of functionally dependent patients requires particular
      attention because of the following conditions: invariably a poor general health
      status leading to a reduced demand for any essential dental or prosthetic care,
      poor socio-economic circumstances, and a lack of support services. The purpose of
      this paper, through a case report, is to highlight the positive effect of
      prosthetic treatment on the quality of life. The patient, a 46-year-old female
      suffering from SM, was referred to our clinic by her general practitioner. Both
      intra-oral and x-ray examinations indicated a severely neglected state of dental
      health including a large number of carious lesions, and advanced periodontal
      disease. On the basis of these findings all of her remaining teeth were removed.
      Six weeks following surgery a start was made to make a full, removable denture
      using the conventional technique. When taking the functional impression, borders
      of the custom tray were extended as far as possible to fully accommodate the
      denture bearing mucosa. This functional adaptation along the posterior border of
      the upper tray led to a significantly greater palatal seal thereby greatly
      increasing stability of the upper denture. An acceptable retention of the lower
      plate was achieved by utilizing tongue function with the modelling compound.
      Taking into consideration functional tooth positioning and biomechanical
      principles, the occlusal plane was positioned close to the lower alveolar ridge,
      and then a bilateral balance and lingualised occlusion were performed. Following
      polymerisation of the denture base, the remontage technique was used to modify
      the balanced forced occlusion. By using the conventional technique and taking
      into account particular biomechanical and psychosocial considerations, the
      successful masticatory functions of the patient were achieved. To achieve an
      optimal prognosis, priorities should be determined during the treatment planning
      stages.

PMID- 15495542
TI  - [Effectiveness of psychotherapy in the treatment of denture intolerance.
      Evaluation of 25 cases].
AB  - 25 "problem-patients" of the Clinic of Prosthetic Dentistry participated in this
      study (21 female, 4 male, aged between 32-81 yr.; mean age: 56.92+/-12.09). All
      included therapies were provided by dentists specialised in psychotherapy, and
      the efficacy of our model to treat denture intolerance patients was analysed
      based on the time need, and other parameters. Psychiatric diagnostic (ICD-10)
      categories were: F20-29: 12%; F30-39: 40%, F40-48: 36%; F60-69: 12%. The efficacy
      of the provided psychotherapy was: recovery in 44% (patient accepted the
      denture); improvement in 32% (patient compromised to accept the denture); no
      effect in 24% (the patient did not accept the denture). Number of
      psychotherapeutic sittings ranged: 1-10 in 24%; 10-20 in 28%, 20-30 in 16%, 30-40
      in 8%; 40-50 in 8%; 50-60 in 12%; and 80-90 in 4% of the cases. Our results
      indicate that, the efficacy of dentists specialised in psychotherapy is
      appropriate to treat denture intolerance patients. However, treatments are rather
      time consuming, and 24% of the cases are unsuccessful. Because of this, the
      prevention and early diagnosis of this problems are crucial.

PMID- 15495543
TI  - Stimulus gender and emotional difficulty level: their effect on recognition of
      facial expressions of affect in children with and without LD.
AB  - The ability to recognize emotions that were easily identifiable and those that
      were more difficult to identify, as expressed by male and female faces, was
      studied in 48 nondisabled children and 76 children with learning disabilities
      (LD) ages 9 through 12. On the basis of their performance on the Rey Auditory
      Verbal Learning Test and the Benton Visual Retention Test, the LD group was
      divided into three subgroups: those with verbal (VD), nonverbal (NVD), and both
      verbal and nonverbal (BD) deficits. A shortened version of Ekman and Friesen's
      Pictures of Facial Affect, including pictures of both men and women, was the
      measure of ability to identify facial expressions of affect. Children of both
      genders in all three groups of children with LD, as well as their normally
      achieving peers, were more accurate in identifying expressions of affect from
      female faces, notwithstanding differences in sensitivity to such emotional
      communication in favor of the nondisabled and VD groups. However, a significant
      interaction was found between gender and emotional recognition difficulty level,
      with female faces being more expressive for emotions that were difficult to
      recognize.

PMID- 15495544
TI  - Learning disabilities and ADHD: overlapping spectrumn disorders.
AB  - Clinical and psychoeducational data were analyzed for 119 children ages 8 to 16
      years who were evaluated in a child diagnostic clinic. A learning disability (LD)
      was present in 70% of the children with attention-deficit/hyperactivity disorder
      (ADHD), with a learning disability in written expression two times more common
      (65%) than a learning disability in reading, math, or spelling. Children with LD
      and ADHD had more severe learning problems than children who had LD but no ADHD,
      and the former also had more severe attention problems than children who had ADHD
      but no LD. Further, children with ADHD but no LD had some degree of learning
      problem, and children with LD but no ADHD had some degree of attention problem.
      Results suggest that learning and attention problems are on a continuum, are
      interrelated, and usually coexist.

PMID- 15495545
TI  - The IQs of children with ADHD are normally distributed.
AB  - The purpose of this investigation was to determine whether or not attention
      deficit/hyperactivity disorder (ADHD)-when there was an absence of reading
      problems-was associated with having a high IQ. The vocabulary and block design
      short forms of the Wechsler Intelligence Scale for Children-Third Edition were
      administered to 63 children with ADHD, 69 children with reading difficulties
      (RD), and 68 children with comorbid ADHD + RD. Results indicated that the
      distributions of estimated Full Scale IQs (FSIQ) for each of the three groups of
      children did not differ significantly from a normal distribution, with the
      majority of children (more than 50%) in each group scoring in the average range.
      The percentage of children with ADHD who scored in the above-average range for
      FSIQ was not significantly higher than the percentages of children in the other
      two groups. No significant group differences emerged for estimated FSIQ,
      vocabulary, or block design. It was concluded that children with ADHD are no more
      likely to have an above-average IQ than are other children.

PMID- 15495546
TI  - Follow-up of children with early expressive phonology disorders.
AB  - Fifty-two children identified at age 4 to 6 years as demonstrating a moderate to
      severe expressive phonology disorder were followed to the third and fourth
      grades. Children were classified into two groups based on the presence of an
      early phonology disorder in isolation (P) or the presence of a phonology disorder
      with other language problems (PL). At follow-up, articulation measures failed to
      differentiate the groups; however, the PL group performed more poorly than the P
      group on measures of phoneme awareness, language, reading decoding, reading
      comprehension, and spelling. The P group demonstrated poor spelling skills
      relative to their reading and language abilities, suggesting residual spelling
      weaknesses in these children. The PL group reported more nuclear family members
      with speech-language disorders and with reading disorders than the P group.
      Findings support previous research linking early language disorders with later
      reading difficulties.

PMID- 15495547
TI  - Factors enhancing sustained use of research-based instructional practices.

PMID- 15495548
TI  - Putting struggling readers on the PHAST track: a program to integrate
      phonological and strategy-based remedial reading instruction and maximize
      outcomes.
AB  - PHAST (for Phonological and Strategy Training) is a research-based remedial
      reading program that attempts to capitalize upon current research on reading
      disabilities and their remediation. The focus of the program is on the primary
      obstacles to word identification learning and independent decoding that most
      disabled readers face and the steps necessary to help these children achieve
      independent reading skills. A framework of phonologically based remediation was
      used as a foundation upon which a set of flexible and effective word
      identification strategies were scaffolded in an integrated developmental
      sequence. The program uses a combination of direct instruction and dialogue-based
      metacognitive training, with the pedagogical emphasis shifting from an initial
      direct instruction, remedial focus to increasingly metacognitive-strategy-based
      methods. A continuum of intervention over 70 hours provides both (a) remediation
      of the basic phonological awareness and letter-sound-learning deficits of
      disabled readers and (b) specific training of five word identification strategies
      that offer different approaches to the decoding of unfamiliar words and exposure
      to different levels of subsyllabic segmentation. Explicit instruction in the
      application and monitoring of multiple word identification strategies and their
      application to text-reading activities continues throughout the PHAST Program.
      PHAST training provides the disabled reader with the opportunity to become a
      flexible reader who approaches new words in or out of context with multiple
      strategies and has the ability to evaluate the success of their application. The
      PHAST Program was developed following the controlled evaluation of its components
      in laboratory classroom settings and recent positive results from their
      sequential combination. PHAST represents a new integrated approach to programming
      in this area using instructional components that have already demonstrated their
      efficacy with children with severe reading disabilities.

PMID- 15495549
TI  - Grouping for reading instruction: does one size fit all?
AB  - Twenty-nine third-grade teachers and selected students from their classes
      participated. Study 1 used teacher interviews and classroom observations to
      examine teachers' perceptions and practices for grouping for reading instruction;
      Study 2 examined the impact of these grouping practices on the academic progress,
      social progress, and attitudes about reading of students representing a range of
      achievement levels, including students with learning disabilities. Results
      indicated that, overall, teachers used whole class instruction for reading and
      the same materials for all students, including students with learning
      disabilities. Students with learning disabilities made little academic progress
      and their attitudes about reading did not improve over time.

PMID- 15495550
TI  - Characteristics of children referred for evaluation of school difficulties who
      have adequate academic achievement scores.
AB  - Forty children (7 to 11 years old) referred for evaluation of learning problems,
      who had scores within the normal range on standardized measures of academic
      achievement, were compared to 81 similarly referred children who had scored low
      (< 90) on at least one measure of academic achievement. We tested the hypothesis
      that children with normal achievement scores who are referred for evaluation of
      learning problems show neuropsychological profiles comparable to those of
      children with low achievement. Referral problems, school history, IQ, academic
      achievement, and neuropsychological function were evaluated. Referred children
      with normal achievement scores came from more advantaged backgrounds and had less
      intensive academic interventions, higher IQs, and better decoding skills.
      Nonetheless, the two groups showed similar neuropsychological profiles.
      Vulnerability to complexity and decreased automaticity were prominent. Normal
      range achievement test scores among children referred for evaluation should not
      be regarded as indicating absence of neurodevelopmental vulnerability.

PMID- 15495551
TI  - [Bicentennial of the Krakow Department of Forensic Medicine (1804-2004)].
AB  - Due to the bicentennial jubilee of the Krakow Department of Forensic Medicine a
      session of the XIII Scientific Conference of the Polish Forensic Medicine and
      Criminology Society will be devoted to its work. The Conference will be held in
      Krakow on the 15-17 of September 2004. Unpublished archive materials associated
      with the beginnings of the Department will be presented.

PMID- 15495552
TI  - [Polymorphism of the YCAII locus in a Polish population].
AB  - This paper describes the polymorphism of a YCAII locus in a Polish population
      sample of 189 males. In an analyzed population sample 6 of 11 alleles identified
      to date were found (www.ystr.org). The most frequent allele was 19 with a
      frequency of 0.4343. The calculated gene diversity value for YCAII locus is 0.62
      and possesses a rather moderate discrimination power for loci analyzed in our
      population to date. Comparison of homogeneity distribution of YCAII alleles
      between different populations was analyzed. Very significant statistical
      differences (p<0.0000) were observed between our population and Italian, German,
      Lithuanian, Latvian and Estonian populations. No statistical differences were
      observed between the Polish and Slovenian population sample (p=0.40).

PMID- 15495553
TI  - [Polymorphism of the DXS1062 locus in a Polish population].
AB  - This paper presents the results of a population study of a dinucleotide STR
      marker DXS1062. Blood samples were obtained from unrelated adult individuals
      (males and females) living in the northern part of Poland. In the analyzed
      population, 21 different phenotypes and 9 alleles of the DXS1062 locus were
      found. The alleles were sequenced and used for the construction of an allelic
      ladder. The nomenclature in accordance with ISFG guidelines was proposed. The
      most frequent alleles were 20 and 21. Statistical parameters (PR, PM, PD, PIC)
      showed that the examined system is useful in forensic medicine.

PMID- 15495554
TI  - [Rare, out-ladder alleles at the STR loci in the population of Upper Silesia].
AB  - Among individuals (participants of paternity testing) from the Upper Silesia
      region rare, out-ladder alleles in four STRs (routinely used in paternity
      testing) were found. There are alleles: VWA*12 and 21, CSF1PO*16, D13S317*6 and
      TPOX*5 with the following frequency: 0.0006 and 0.0006, 0.0005, 0.0006 and
      0.0005.

PMID- 15495555
TI  - [Mono- and dizygotic twins in forensic paternity testing in practice at the
      Department of Forensic Medicine (Silesian Academy of Medicine, Katowice) in the
      years 1996-2003].
AB  - Giving an opinion on disputable paternity, concerning monozygotic twins in
      practice at the Department of Forensic Medicine (Silesian Academy of Medicine,
      Katowice) demonstrated their ideal agreement according to examined genetic
      markers possible. Even the mutation, which was revealed using the RFLP-VNTR
      method was the same for both twin sisters. In the case of dizygotic twins a firm
      differentiation of paternity index and probability of paternity was proved. This
      was the consequence of independent features segregation in first, reductive
      meiotic division. While the rare, out-ladder allele 16 at the CSF1PO locus was
      transmitted to both twins: a daughter and a son by the putative father.

PMID- 15495557
TI  - [Hair analysis in the evaluation of complex drug-poisonings for medico-legal
      purposes].
AB  - Among various alternative materials used in toxicological analysis the most
      important is hair, in which xenobiotics deposited create a possibility to observe
      the history of their administration in the period determined by the hair-length.
      In this paper the authors have tried to outline the course of the application of
      hair analysis in forensic toxicology for medicolegal purposes. The undertaken
      subject has been recorded in four cases of complex drug poisonings in which hair
      analysis was used in the toxicological evaluation. Drugs detected in the hair of
      the examined subjects inform about the history of pharmacological therapy in
      confrontation with those administered in order to commit suicide. The analysis
      confirms a model of dependence and proves drinking of alcohol and use of cocaine
      during the pharmacological therapy of dependence.

PMID- 15495556
TI  - [Selected alcohols on the pro- and anti-oxidative processes in rat erythrocytes].
AB  - In forensic medicine practice poisonings are rather frequent, and among them,
      those caused by fatal "substitution" of ethyl alcohol. One of the most frequently
      encountered "substitutes" for ethyl alcohol is methanol. The purpose of our
      research was to determine the concentration of malonic dialdehyde as the
      expression of lipid peroxidation and antioxidant enzyme activity after dosed
      chronic ethyl and methyl alcohol intoxication. The experiment was conducted on
      approx. 6 month-old male inbred Lewis rats each weighing approx. 250 g. Ethanol
      and methanol solution was given in the concentration 1.0 M. The control group of
      rats received water. Each experimental group numbered 30 rats, this number was
      divided into three sub-groups, which were put-down at 4, 8 and 12 weeks. The
      activity of superoxide dismutase (CuZu-SOD) was determined by the Misra-Fridovich
      method, catalase (CAT) by the Beers-Sizer method. The concentration of malonic
      dialdehyde (MDA) was determined using the method of Placer et al. by assessing
      the concentration of TBARS compounds. Results are expressed as a mean +/- SD. The
      paired Student's test for small groups were used. Superoxide dismutase SOD1
      activity decreased compared with the control group throughout the duration of the
      experiment from 2212 U/gHb to 1676 U/gHb for ethanol and from 2212 U/gHb to 945
      U/gHb for methanol. Catalase activity for methanol decreased from 9.1 U/gHb to
      5.1 U/gHb, for ethanol to 7.4 U/gHb. In the 4th week of the experiment increase
      of malonyl dialdehyde concentration for methanol group was observed--from 0.14
      umol/gHb to 0.34 umol/Hb; after 8th weeks it decreased to 0.2 umol/gHb and in the
      12th week increased to 0.23 umol/gHb. For ethanol these changes was less visible
      and reached the level of 0.24 umol/l. The statistical processing of the results
      was performed on the basis of parametric tests (the t-Student test for small
      experiments) and computer software Statistica. The statistical significance was
      set for p<0.05.

PMID- 15495558
TI  - [Inconsistencies between clinical and forensic recognition of brain concussion in
      the material of the Department of Forensic Medicine of the Medical Academy in
      Bydgoszcz].
AB  - The material contains 128 cases of brain concussion diagnosed by physicians since
      1995 to 2000. The bases of diagnosing and the rules of opinionating of brain
      concussion after trauma of the head were discussed. Inconsistencies between
      clinical diagnosis and forensic medical opinionating were observed in 69.53%. In
      the group of patients who were intoxicated at the moment of head trauma
      disagreement was observed in 91.30%.

PMID- 15495559
TI  - [Domestic violence towards children in the material of the Department of Forensic
      Medicine of the Medical Academy in Bydgoszcz].
AB  - The aim of the paper was to analyze the phenomenon of domestic violence towards
      children. The paper was based on the results of forensic and medical
      investigations carried out at the Department of Forensic Medicine in The Medical
      Academy in Bydgoszcz between the year 1995 and 2000. Various, i.e. physical,
      psychological and moral forms of maltreatment were considered. The perpetrators
      were more often children's fathers and victims were more often boys over 10.
      Injuries were found most often in the lower extremities and the heads and rarely
      in the upper extremities, the trunk and the neck.

PMID- 15495560
TI  - [Regulations of the ethical evaluation system of scientific and clinical research
      in connection with Poland joining the European Union].
AB  - The author has discussed the procedures of the Bioethical Commission of a
      biomedical research assessment and clinical trials based on analysis of the
      directives of the European Commission. Particularly criticized was the omission
      of the role of local committees in the case of the multi-center studies. Also
      underlined was a necessity to inform the examined persons, in a wider and more
      understandable fashion, about an essence of the examination and the expected
      level of risk.

PMID- 15495561
TI  - [Child abuse syndrome].
AB  - The aggrievement of children is not only a present day problem. The term: child
      abuse has appeared in the literature in the mid XIX century. In this paper an
      attempt has been made to reference this phenomenon in region of Bydgoszcz. There
      were 2889 cases of children with bodily injuries requiring hospital treatment in
      the years 1992-1996. 10 cases were victims of long lasting violence in their
      homes. This paper also presented the basic regulations and pays attention to the
      requirement of greater engagement of the whole society. A restrictive system of
      child protection can contribute to a significant decrease in the scale of this
      phenomenon. Scandinavian countries can be used as an example of such an approach.

PMID- 15495562
TI  - [Positional asphyxia as a cause of death in a traffic accident with the driver-
      in the "upside-down car position"].
AB  - We demonstrate a case of positional asphyxia of the car with the driver in the
      upside-down position following a traffic accident. The discussion shows the
      confirmity of this type of death mechanism with the facts estimated during the
      investigation of the place of the accident and autopsy.

PMID- 15495563
TI  - [The use of entomologic methods in determining the time of death--case studies].
AB  - This paper describes a number of cases in which the determination of the time of
      death was based on entomological methods. These cases took place in the Pomorskie
      Province, and the autopsies were carried out in the Department of Forensic
      Medicine, Medical University of Gdansk.

PMID- 15495564
TI  - [Tuberculosis: a challenge we must face].

PMID- 15495565
TI  - [Autopsy of the corpse of his Excellency Libertador General Simon Bolivar. 1830].

PMID- 15495566
TI  - [The suffocating presence of the body].
AB  - A brief reflection is presented on tuberculosis as a paradigm of disease and its
      relationship with human behavior based on Thomas Mann's The magic mountain. The
      romantic myth of tuberculosis is analyzed as a disease prevailing among
      psychologically sensitive people. This myth is compared with present day health
      expectations as a consequence of widespread information produced by the tireless
      efforts of the medical sciences.

PMID- 15495567
TI  - [Demonstration of tuberculosis by DNA ribotyping of Mycobacterium tuberculosis in
      a Colombian prehispanic mummy].
AB  - The mummy studied belonged to the prehispanic Guane society. According to the Mom
      003 record of the Archaeological Museum of the House of the Marques de San Jorge,
      it was found in a cave in the department of Santander, Colombia, and was donated
      to the Culture Promotion Fund of the Banco Popular more than 30 years ago. The
      gender of the mummy had been previously determined by PCR study of the Y
      chromosome; computerized tomography studies (CT) were carried out and samples of
      lung tissue, vertebral spine and skin were taken for studying tuberculosis. The
      CT scans clearly show the presence of spinal tuberculosis, accounting for its
      important angular cifosis or Pott's disease. DNA obtained from lung tissue was
      submitted to ribotyping with genes of the 16S ribosomal subunit, giving positive
      results. This finding demonstrates the presence of tuberculosis in prehispanic
      Colombia.

PMID- 15495568
TI  - [Memories of an antituberculous sanatorium].
AB  - A summary of the existence of the Hospital San Carlos in Bogota as an
      antituberculous sanatorium is presented. Its origins, architectonic aspects of
      its building, the criteria with which it was equipped with state of the art
      scientific equipment and elements and the excellent facilities for attention of
      inpatients during their prolonged hospital stay are presented. The life of a
      sanatorium in the pre-antibiotic era, the changes in its routine brought upon by
      the introduction of effective anti-TB drugs as well as the evolution of
      treatments which eventually led to the disappearance of sanatoriums, with all its
      traumatic effects on the hospitals which had been specifically built for this
      purpose, are described. The contributions made by the hospital to the different
      medical and surgical aspects of TB management and to the introduction of
      effective short course ambulatory treatment regimens are also referred. Mention
      is also given to the rescue of this memory, an important part of the Health
      Sciences Museum which will shortly open in Bogota.

PMID- 15495569
TI  - [Paradoxical appearance of encephalic tuberculomas during treatment for
      tuberculosis in immunocompetent patients].
AB  - Two cases of appearance of encephalic tuberculomas during anti-tuberculous
      treatment in immunocompetent patients are presented. The first an adult man
      presenting a right frontal lesion which required surgical treatment and the
      second a girl with multiple lesions located mainly in the brainstem. This
      paradoxical presentation is attributed to a bizarre immunological reaction
      between the host and the tuberculosis bacillus. Patients with this condition do
      not require changes in anti-tuberculous treatment, and steroids are helpful in
      alleviating the symptoms. Surgery is indicated only for cases of uncontrollable
      intracranial hypertension or when there is diagnostic uncertainty. The prognosis
      of this entity is usually good.

PMID- 15495570
TI  - [Polymorphism of TNF-alpha in autoimmunity and tuberculosis].
AB  - Tumor necrosis factor alpha (TNF-alpha) has been incriminated in several
      autoimmune and infectious diseases. The influence of TNF-alpha -308 polymorphism
      was examined in patients with systemic lupus erythematosus (SLE), rheumatoid
      arthritis (RA), primary Sjogren's syndrome (pSS) and tuberculosis. Genomic DNA
      from patients with RA (N=165), SLE (N=118), pSS (N=67), tuberculosis (N=138), as
      well as ethnic-matched controls (N=419) were characterized for the TNF-alpha -308
      genetic polymorphism using the polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP) method. TNF2 allele was associated with RA (OR:
      1.6, C.I.95% 1.2-2.3, p=0.008), SLE (OR: 2.3, 95%C.I. 1.6-3.3, p<0.0001), and pSS
      (OR: 2.7, 95%C.I. 1.7-4.1, p<0.0001). TNF1 was associated with tuberculosis (OR:
      1.9, 95%C.I. 1.2-3.1, p=0.02). TNF1/TNF2 heterozygosity was associated with
      susceptibility for RA (OR: 1.7, 95%C.I. 1.2-2.6, p=0.01), SLE (OR: 3, 95%C.I. 2
      4.7, p<0.0001), and pSS (OR: 3.8, 95%C.I. 2.2-6.5, p<0.0001). The homozygous
      state TNF1/TNF1 was protective for autoimmunity (OR<0.6, p<0.01). In contrast,
      the TNF1/TNF2 genotype was a protective factor for tuberculosis (OR 0.5, 95%C.I.
      0.3-0.9, p=0.02) whereas TNF1/TNF1 homozygosity was associated with
      susceptibility (OR: 2, 95%C.I. 1.2-3.4, p=0.02). These results indicate that TNF2
      is a common susceptibility allele for autoimmune rheumatic diseases and a
      protective one for tuberculosis. In addition, the data point towards a genetic
      selection in our population that might be maintained through dominant selection
      (heterozygote advantage) to infection by M. tuberculosis but susceptible to
      autoimmunity.

PMID- 15495571
TI  - [Five year experience with thin layer agar medium for rapid diagnosis of
      tuberculosis].
AB  - Tuberculosis represents a public health problem worldwide, mainly in developing
      countries where 95% of the cases occur. New technologies that support rapid
      diagnosis are not available in these settings because of high cost. New, rapid,
      and less expensive techniques are necessary before diagnosis can be improved in
      these areas. The present work compared the performance of a rapid and costly
      culture media, thin layer agar (CD7H11), with the traditional Lowenstein-Jensen
      (LJ) culture method. For this comparison, 1,809 clinical specimens were processed
      for diagnosis of mycobacterial infections. Clinical samples were processed
      according to standard procedures and cultured concomitantly in LJ and CD7H11. The
      times required to obtain an isolate were compared for culture media. Sensitivity
      (S), specificity (Sp), predictive values (PPV, NPV) and agreement (kappa
      coefficient) were calculated for CD7H11, with LJ serving as the gold standard.
      CD7H11 showed S to be 73.5% (C.I.95%: 69.6-80.4), Sp to be 99.2% (C.I.95%: 98.8
      99.6), PPV 90.4% (C.I.95%: 85.3-95.6) and NPV 97.6% (C.I.95%: 96.8-98.3).
      Agreement had a kappa coefficient of 0.52. The mean time for CD7H11 was 11 days
      (SD+/-4.9) compared with 26.5 (SD+/-8.6) days for LJ. Similar results were
      obtained in a comparison of respiratory and multibacillary clinical samples. In
      extrapulmonary samples and those with lowered bacillus count, CD7H11 demonstrated
      a lower sensitivity. The concomitant use of both culture media enhanced
      sensitivity of detection. CD7H11 proved a simple and rapid technique for
      culturing mycobacteria and can be combined with traditional methods for improving
      laboratory capability for diagnosis of tuberculosis.

PMID- 15495572
TI  - [Distribution of PRA patterns of clinical isolates of the Mycobacterium avium
      complex from Spain and South America].
AB  - Mycobacterium avium complex (MAC) infections are the most frequent systemic
      infections associated with advanced AIDS. DNA probes for accurate identification
      of mycobacteria are available but are very expensive in many Latin American
      settings. Consequently, most Latin American diagnostic laboratories employ
      inaccurate and outdated tests for mycobacteria identification. Therefore, PCR
      restriction analysis (PRA) of the hsp65 gene was evaluated for the identification
      of 163 MAC human isolates originated from Spain and South America. The
      predominant PRA type in each country was: M. avium type I in Argentina (23/42,
      55%) and Brazil (48/72, 67%), M. avium type II in Spain (18/26, 69%) and M. avium
      type III in Colombia (10/23, 43%). The Colombia frequency is noteworthy, since
      the PRA type III was quite infrequent in the other three countries. Furthermore,
      its presence has not been reported outside the Americas. The advantages and
      disadvantages of PRA in diagnostic mycobacteriology are discussed.

PMID- 15495573
TI  - [Surgical treatment of multiresistant lung tuberculosis].
AB  - Drug resistance has become a major problem in the treatment of tuberculosis.
      Pulmonary resection in combination with chemotherapy appears to be an effective
      measure for the treatment of multi-drug resistant pulmonary tuberculosis. A
      retrospective review was performed of the medical and laboratory findings of 28
      patients with multi-drug resistant tuberculosis who underwent pulmonary resection
      for pulmonary tuberculosis between January 1990 and December 2000 at La Maria
      Hospital, Medellin. Twenty-one of them had medical therapy before surgery; 14
      patients underwent upper lobectomy and 10 patients pneumonectomy). The AFB
      negative sputum conversion rate was 88.9% (25/27) after surgery, during an
      average of 6 weeks. Bacteriological relapses were confirmed in 6 of 27, 4 of
      these 6 had AFB negative sputum. Twenty-eight patients had medical therapy after
      surgery. For selected patients, pulmonary resection in combination with
      chemotherapy should be considered an effective measure for treatment of multi
      drug resistant pulmonary tuberculosis.

PMID- 15495574
TI  - [Initial drug resistance as a threat for tuberculosis control: the case of
      Buenaventura, Colombia].
AB  - In 2001, Buenaventura, Colombia, the rate of smear-positive pulmonary
      tuberculosis was of 66 per 100,000 inhabitants. The poor control of the
      tuberculosis in this city during the last 10 years and the inadequate use of
      first-line anti-tuberculosis drugs was an opportune situation for the development
      of high resistance to these drugs. Two surveys of initial resistance to first
      line antituberculosis drugs were conducted in new cases of pulmonary TB, in the
      city of Buenaventura--the first from August 1, of 1997 to January 31 of 1998 and
      the second from November 15, of 2000 to November 15, 2001. The method of multiple
      proportions was used to determine drug susceptibility. Mycobacterium tuberculosis
      was isolated in 93% and 55% of the new cases of lung TB during each respective
      period. The initial resistance to at least one drug was 25% (9/36) and 32%
      (23/72), respectively. The initial multi-drug resistance (defined as resistance
      to at least isoniazid and rifampicin) was 6% for both surveys. This demonstrates
      the dissemination of multidrug-resistant bacilli and shows the need for
      surveillance of resistance to antituberculosis drugs in control of the disease,
      particularly in those areas where the TB control program has been erratically
      applied. In areas where multi-drug resistant TB occurs, the control strategy
      should be enhanced with the careful introduction of second-line drugs.

PMID- 15495575
TI  - [Surveillance of resistance of Mycobacterium tuberculosis to anti-TB drugs in
      Cuba, 1995-1998].
AB  - Drug-resistance surveillance by means of culture and drug susceptibility test
      (DST) allows the estimation of the regional and global magnitude of multidrug
      resistance (MDR). Two reports on anti-tuberculosis drug resistance by the
      WHO/IUATLD showed that drug-resistance TB varied widely across regions. This work
      determined the prevalence of drug resistance among new cases and among previously
      treated cases of tuberculosis in Cuba during the period 1995-1998. Drug
      resistance was determined using the proportion method in 1379 Mycobacterium
      tuberculosis strains to first line antituberculosis drugs (isoniazid,
      streptomycin, ethambutol and rifampicin). The resistance in new cases was 8.3%
      and 6.5%; MDR was 0.7% and 0% in the first and second study respectively. The
      contributed data through Cuba demonstrated that our country is relatively free of
      MDR strains, recognizing it to world level the good tuberculosis-control programs
      and the success of the application in our country of the directly-observed
      treatment strategy from the year 1971.

PMID- 15495576
TI  - In vitro susceptibility testing of Mycobacterium tuberculosis complex strains
      isolated from seals to antituberculosis drugs.
AB  - Mycobacteria strains belonging to the Mycobacterium tuberculosis complex were
      isolated from seals found in the South Atlantic. The animals were received in
      Mundo Marino installations and treated for Mycobacterium tuberculosis complex by
      conventional therapy of intensive care and enriched food supply; however, in all
      cases treatment failed. Necropsies of all animals revealed extensive lesions
      compatible with tuberculosis involving lungs, liver, spleen and lymphatic nodes.
      Classical biochemical methods as well as molecular techniques using the IS6110
      probes were performed for mycobacterial identification. Furthermore, the LCx M.
      tuberculosis assay (Abbott Laboratories) identified all strains as Mycobacterium
      tuberculosis complex members. The in vitro susceptibility pattern was examined in
      mycobacterial strains isolated from seven seals and in 3 reference strains--BCG,
      H37Rv (M. tuberculosis) and AN5 (Mycobacterium bovis)--to 4 medications-
      isoniazid, rifampin, streptomycin and ethambutol. Minimal inhibitory drug
      concentrations were determined by the Mycobacterial Growth Indicator Tube (BD
      Argentina) method and a microdilution and colorimetric assay using 3-(4-5
      dimethyltiazol-2)-2,5 diphenyltetrazolium bromide. All the isolates and the
      reference strains BCG and AN5 were inhibited by MIC values similar to those of
      H37Rv with good agreement obtained by both techniques. These findings suggest
      that a therapeutic regimen aimed to seals diagnosed with tuberculosis play an
      important role in the prevention of tuberculosis transmission from infected
      animals to humans that are in routine contact with them.

PMID- 15495577
TI  - [Tuberculosis in the San Jose University Hospital in Popayan, Colombia, 1998
      2000].
AB  - TB is a public health problem in the world. In Colombia the Health 100 Law caused
      changes in prevention programs. The TB control program was compromised too. The
      actions in relation with active looking and examination of respiratory
      symptomatic people has been lowering. This retrospective study describes the
      clinical, epidemiological and medical care characteristics of tuberculosis
      patients attended in the Hospital Universitario San Jose de-Popayan. The clinical
      expedients and laboratory registers were investigated. 120 cases of 187
      registered patients were included; finally only 89 were tuberculosis cases: 39
      pulmonary (43.8%) and 50 extrapulmonary (56.2%). The extrapulmonary forms were:
      miliar, 39 patients; pleural, 4: of lymph nodes, 3; osteoarticular, 2, and
      meningitis, 2 cases. 49% of patients were 15-59 years old, 28% more than 59;
      males 64% and 65% coming from country areas. Ziehl Neelsen (ZN) smear was
      positive in 22% of 59 sputums of pulmonary TB and 20.2% of 94 extrapulmonary TB
      samples: mycobacteria culture positive in 14.3% of 14 pulmonary TB sputum, and
      29.6% of 54 extrapulmonary TB samples. The media days into hospital/yard was 4-26
      and the media days to begin tuberculosis treatment/yard was 4-8. In summary there
      are important request for TB medical care to universitary hospital, however the
      diagnosis is difficult and takes a long time while mycobacteria can be
      transmitted to hospital contacts. It is necessary to get a better efficiency of
      diagnostic tests in the hospital and appropriated survey of the cases that begin
      treatment.

PMID- 15495578
TI  - [Situation of tuberculosis in Colombia, 2002].

PMID- 15495579
TI  - [Trends of tuberculosis related mortality and hospital discharges before and
      after the implementation of the health sector reform, Colombia, 1985-1999].
AB  - We describe the changes that have been presented in the tendencies of mortality
      and hospital discharges by tuberculosis (TB) between 1985-1999, period before and
      during the implementation of the Health Sector Reform (HSR) in Colombia. For it,
      we carried out an exploratory descriptive study with analysis of time series of
      hospital discharges and mortality rates of TB in Colombia. It was found that
      although starting from 1991 the Series approach stabilized, their tendencies
      showed a significant descent diminishing both in 30% between 1985 and 1990. The
      steady trend registered from 1991 to 1999, could be explained by deterioration of
      the primary care during this period, also due to other complex social processes
      occurred in Colombia during this decade, which barred the continuing the descent
      trend in hospital discharges and mortality due to TB previously registered. Due
      to the study design limitations we cannot establish causal relationships between
      these trends and the health sector reform in the country; we recommend the
      improvement the health sector performance about public health problems such as TB
      in order to avoid unnecessary hospitalizations and deaths due to causes
      responsive to health sector interventions.

PMID- 15495581
TI  - [Overview of the HIV/tuberculosis coinfection in Bogota, Colombia, 2001].
AB  - The magnitude and characteristics of the co-infection of TB-AIDS was evaluated in
      cases reported in Bogota, 2001. A cross sectional study was carried out using the
      epidemiological registry of TBC-AIDS cases from the Health Secretariat of Bogota.
      Only TB cases with a positive HIV test were included in. Of 950 TB cases reported
      in Bogota, 113 (11.9%) were indicated to have TB and HIV positive tests;
      epidemiological information was recovered from 103 of them. Most cases were male
      (male:female ratio was 12:1); 38.8% were between ages 25 to 34; 40.8% of cases
      belonged to the contributive regime; 82% were new cases. Of the 105 cases, 62%
      were classified with the pulmonary form of TB and 30% with extra pulmonary
      disease. In the last group, the most frequent form was lymph node tuberculosis.
      Diagnostic criteria were recorded for only 55 patients; however, 78% were
      confirmed with microscopic smears. Procedural data were available for 29 patients
      in the first phase of treatments; 86.2% had received therapy recommended by the
      Ministry of Health. The failures of TB control programs indicated by statistical
      data, do not reflect patient's activities that may be contributing to greater
      infection risk. Additional monitoring may be necessary to fortify the current TB
      control program.

PMID- 15495580
TI  - [Respiratory syntomatic prevalence, infection and tuberculosis disease and
      associated factors: population-based study].
AB  - A cross sectional survey on TB epidemiological characteristics was carried out in
      Mitu (Vaupes, Colombia) with the aim of measuring the prevalence of TB cases, the
      prevalence of TB suspected cases, the coverage with BCG vaccine and the
      prevalence of infection with Mycobacterium tuberculosis. One hundred and sixty
      five (165) households were included in the survey using a randomized cluster
      sampling design (n=20 clusters) which yielded a sample size of 972 subjects. The
      prevalence of TB suspect cases was 3.6% (C.I.95% 2.6-4.9%); coverage with BCG
      vaccine was 94%. Vaccinated people had a lower chance of being a TB suspected
      case (OR=0.37 C.I.95% 0.15-0.95). TB prevalence was 1.4%. People vaccinated with
      BCG had a lower chance of having been a TB case (OR=3.3 C.I.95% 1.0-14). These
      data recommend that 10% of people with respiratory symptoms be screened for in
      the National Control Program,and that the results be reviewed with surveys based
      at health centers. The data also reinforce the need for better vaccination
      coverages with BCG in high endemic areas.

PMID- 15495582
TI  - [Effects of the health sector reform upon tuberculosis control interventions in
      Valle del Cauca, Colombia].
AB  - Implementation of the General System of Social Security in Health (GSSSH) was
      initiated for the control of tuberculosis (TBC) in the state of Valle del Cauca,
      Colombia, between 1991-2000. A study of its effects was centered in 7
      municipalities of Valle del Cauca with a complementary set of qualitative and
      quantitative techniques for data collection and analysis. A reduction in
      planning, control and regulation of TBC activities by state agencies was
      observed. New administrative structures and new funding sources did not produce
      the expected positive effects on tuberculosis control. Instead, the quantity and
      quality of tuberculosis control activity were reduced as a consequence of the
      health sector reform. In conclusion, GSSSH implementation affected negatively
      tuberculosis control activity.

PMID- 15495583
TI  - Recent advances in molecular methods for early diagnosis of tuberculosis and drug
      resistant tuberculosis.
AB  - Tuberculosis (TB) remains the main infectious cause of deaths in the world. Due
      to the slow metabolism of the causative agent, Mycobacterium tuberculosis, the
      isolation, identification and drug susceptibility testing requires several weeks.
      New techniques have improved specificity, turnaround time and cost effectiveness.
      Although these methods yield results within hours from sample collection, the
      clinical significance of each positive result requires rigorous evaluation in
      most cases. Herein the advantages and disadvantages of the most promising
      molecular techniques for detection of TB and drug resistance are discussed.

PMID- 15495584
TI  - The other face of Janus.

PMID- 15495585
TI  - [Gene inactivation in Mycobacterium tuberculosis and its use in tuberculosis
      control and prevention].
AB  - Availability of the M. tuberculosis genome sequence and the development of
      sophisticated systems for genetic manipulation of bacilli offer the potential for
      new and effective tools to prevent and control tuberculosis. Efficient methods to
      inactivate mycobacterial genes have been developed. These methods have become the
      cornerstone for the application and development of mycobacterial functional
      genomics. Specific mutants are generated to establish the role of targetted genes
      associated with mycobacterial physiology and pathogenesis. Gene inactivation,
      supported directly or indirectly by the deciphering of the mycobacterial genome,
      has permitted the generation of large numbers of M. tuberculosis mutants.
      Analysis of these mutants has (in some cases) established relationships between
      gene products and their role in mycobacterial physiology and pathogenesis.

PMID- 15495586
TI  - Molecular epidemiology of tuberculosis: methodology and applications.
AB  - The resurgence of tuberculosis around the world has renewed interest in
      understanding the epidemiology and pathogenesis of this disease. A revolutionary
      advance in the field of tuberculosis research has been the development of
      molecular techniques that permit identification and tracking of individual
      strains of Mycobacterium tuberculosis. With these techniques, molecular
      epidemiology has been established as a new discipline that adds another dimension
      to the classical epidemiology of tuberculosis and has increased our understanding
      of the transmission dynamics of M. tuberculosis. The increased epidemiological
      knowledge has led to discovery of inadequacies in tuberculosis control programs;
      this information has helped garner resources for program improvement and has
      highlighted the need for the continuous surveillance of tuberculosis. Additional
      genetic methods are being developed based on the knowledge of the genome sequence
      of M. tuberculosis. These simpler and less costly genotyping techniques promise
      to expand the application of molecular epidemiology to developing nations (where
      90% of the disease burden occurs) in support of national tuberculosis programs.
      Furthermore, these tools permit ever more effective probes into the dynamics of
      transmission, the population structure, evolution and pathogenesis of M.
      tuberculosis.

PMID- 15495587
TI  - [New tools for detection of latent tuberculosis].
AB  - Tuberculosis is a serious public health problem worldwide, particularly in
      developing countries. In Colombia, the focus is on the clinical management of
      patients with active disease, but not on preventive programs that identify and
      treat individuals with a latent tuberculosis infection. This review emphasized
      the importance of preventative programs and their critical role in the
      curtailment of infection dissemination in the community. An effective program
      includes chemoprophylactic treatment of household contacts and detection of
      individuals with latent tuberculosis infection and with high risk of reactivation
      of disease. The tuberculin skin test has been used effectively for more than 100
      years, despite inherent sensitivity and specificity limitations. Herein the
      advances provided by a new generation of immunoassays are reviewed, includingthe
      commercially-available Quantiferon and the experimental development of ELISPOT.
      Both are based on the detection of IFNgamma secretion by peripheral T cells upon
      incubation with Mycobacterium tuberculosis antigens. Finally, the importance of
      molecular techniques aimed at detecting DNA from the mycobacterium is discussed
      as a possible complement to the described immunoassays.

PMID- 15495588
TI  - [Management of TB suspected cases of drug resistant tuberculosis requiring a
      second treatment].
AB  - The management of patients with resistance to anti tuberculous drugs is complex
      and therefore must be managed by physician specialists. The most difficult
      patients are the cases in retreatment, where some very different possibilities
      are possible, as abandonment, failures and relapses. Patients with multi-drug
      resistant (MDR) tuberculosis are the most difficult to treat; MDR appears in all
      the failures or non-adherences to the treatment regime. To elaborate a scheme of
      retreatment for these patients, two guidelines must be followed: (1) do not rely
      on outcomes of drug susceptibility tests and (2) a detailed history of drug
      treatment must be considered of paramount importance. With this information, a
      retreatment scheme can be formulated that involves the use of at least three
      drugs not previously taken by the patient. For a successful control of
      tuberculosis, the national tuberculosis programs in Latin American countries must
      assure careful management of newly diagnosed patients. Secondly, if resources are
      available, a bank of second-line drugs must be ready for managing retreatment
      situations (e.g., 3 Z-Kn-Eth-Of/15 Z-Eth-Of) if first line drug treatments fail.
      Using individualized retreatment with second line drugs is recommended only in
      industrialized countries, and for a few middle income countries as a last resort.

PMID- 15495589
TI  - [Perspectives for new anti-tuberculous vaccines in the post-genomic era].
AB  - Vaccination with attenuated Mycobacterium bovis BCG has been used as the routine
      procedure to immunize against tuberculosis. Since the efficacy of BCG vaccination
      is very controversial, the search for new immunoprophylatic tools against
      tuberculosis is an area of intense interest. Knowledge of the complete sequence
      of Mycobacterium tuberculosis (Mtb) H37Rv genome and the application of new
      immunological, biochemical and genetic technologies has led to a detailed
      understanding of the transcriptome and proteome of this bacterium. Approximately
      one-third of the human population is infected with Mtb; however, the bacillus is
      only detected once the symptoms appear and therefore most of the recent efforts
      have been devoted to the development of a post-infection vaccine. In theory, this
      vaccine (1) will give rise to an increase in the long-lasting specific immunity
      against Mtb, (2) will not have significant adverse effects, and (3) will be
      affordable for the people in third world countries. The main strategies that have
      been developed include the subunit vaccines, either as a mixture of relevant
      immunogenic proteins or DNA constructs, recombinant strains of Mycobacterium
      bovis BCG and Mtb, designed to secrete immunogenic proteins or with attenuated
      virulence, respectively, and DNA-based vaccines. The subunit vaccines are
      delivered either as mixtures of immunogenic proteins and adjuvants, or as naked
      DNA or by viral vectors in order to induce a potent Th1 response. Most of these
      vaccines have been tested in several kinds of animal models, but they do not
      fully reproduce the human pathology. However, the results obtained so far are
      very encouraging and have led to the development of phase I trials in humans.

PMID- 15495590
TI  - [Drugs: a world public good?].

PMID- 15495591
TI  - [Make your own diagnosis, first and second part].

PMID- 15495592
TI  - [Idiopathic hypertrophic cranial pachymeningitis].
AB  - Idiopathic hypertrophic cranial pachymeningitis is an infrequent chronic
      inflammatory process of unknown etiology which causes thickening of the dura
      mater and progressive neurologic alterations due to the compression of adjacent
      structures. A case is presented of an adult woman with a clinical syndrome
      consisting of headache, progressive visual loss and bilateral optic neuropathy.
      The diagnosis was based upon visualization of the thickened dura mater in
      neuroimaging studies and the exclusion of known causes by histopathological
      examination. Diagnosis and follow-up of this condition are currently easier with
      the use of nuclear magnetic resonance with contrast medium. Biopsy of the dura
      mater continues to be the gold standard for the definitive diagnosis of this
      disease. Steroid therapy causes clinical improvement in most of the patients;
      however, relapses are frequent, making necessary the concomitant use of other
      immunosuppressive agents such as cyclophosphamide or azathioprine. Mortality is
      low but definitive neurologic sequelae are common.

PMID- 15495593
TI  - [Relapses after multibacillary leprosy treatment].
AB  - Leprosy relapses are mainly due to bacillary persistence and diamino-diphenyl
      sulphone (DDS) monotherapy. Case histories were examined for 33 patients with
      lepromatous leprosy (LL), diagnosed 7-48 years before the relapse and treated
      only with DDS during 4 to 38 years. Twenty-eight patients received irregular non
      supervised polychemotherapy (PCT) since 1983. Five patients received only DDS,
      and presented relapses 13-20 years after the treatment was stopped. Relapses were
      diagnosed by clinical methods, including the reappearance of lesions or presence
      of new anesthetic areas. All cases were confirmed by bacilloscopy, and a subset
      of 20 cases by skin biopsy. Four patients presented indeterminate leprosy (IL)
      and one patient borderline tuberculoid leprosy (BT) in the biopsy. The latter 5
      demonstrated presence of intraneural bacilli; the remainder were LL. Two patients
      relapsed even with PCT treatment. The others were cured with supervised PCT.
      Predisposing factors for relapses were as follows: DDS monotherapy, irregular PCT
      with inadequate dosage, unsupervised treatment, treatment uncompliance, and
      inadequate relationship between the patient and the health staff. Inspections for
      relapse in leprosy is recommended for in all multibacillary patients that were
      treated with DDS. The clinical appearance of new lesions or new anesthetic zones,
      the bacilloscopy and skin biopsy, used together, are effective in establishing
      the presence of relapses.

PMID- 15495594
TI  - [Anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis: relation
      with clinical features, cytokines and HLA-DRB1].
AB  - The specificity and sensitivity of anti-cyclic citrullinated peptide antibodies
      (anti-CCP) was examined in Latin-American patients with rheumatoid arthritis
      (RA). The variables considered included: 1) relation with the activity of
      disease, 2) extra-articular manifestations (EAM), 3) synthesis of cytokines (IL
      4, IL-10, IL-12, TNF-alpha, and IFN-gamma) and IgM and IgA rheumatoid factor
      (RF), and 4) the association with HLA-DRB1 polymorphism. Seventy-nine RA patients
      were assessed (69 with established RA, and 10 with recent-onset RA not receiving
      any treatment), 56 with ankylosing spondylitis (AS), 25 with systemic lupus
      erythematosus (SLE), 50 with primary Sjogren's syndrome (pSS), and 10 healthy
      individuals. Of the 69 patients with established RA, 36 were reexamined 2 years
      later. The activity of the RA was measured by criteria adopted by the American
      College of Rheumatology. Anti-CCP2, RF and cytokines levels were determined by
      ELISA. HLA genotypes were established by first, PCR sequence amplification using
      sequence-specific primers and then, complete sequencing of the product. Anti-CCP
      antibodies were observed in 96% of patients with RA during the first evaluation
      and in 86% at the second evaluation (p = 0.12). No significant change in antibody
      titre was observed between the two evaluations (131 +/- 58.7 and 130.6 +/- 67.1
      IU, respectively). The overall sensitivity and specificity was 94% and 92%,
      respectively; however, at titres > 60 IU, the values were 84% and 95%,
      respectively. The anti-CCP likelihood ratio positive test was 12 and the
      likelihood ratio negative test was 0.06. The positive predictive value was 87%,
      and the negative predictive value was 96%. Anti-CCP antibodies were observed in
      12% of SLE and pSS patients, in 2% of AS patients, and in 10% of healthy
      controls. In RA patients, these antibodies were not associated with the activity
      of disease, EAM or HLA-DRB1 alleles; no significant correlation was observed
      between antibody titre and cytokines level. Although anti-CCP antibodies have
      potential as a diagnostic tool for RA, they are not useful for monitoring
      clinical activity or predicting the clinical course of disease. Antibody
      synthesis is HLA-DRB1 independent and not correlated with Th1/Th2 cytokines.

PMID- 15495595
TI  - [Genetic susceptibility and risk of gastric cancer in a human population of
      Cauca, Colombia].
AB  - Gastric cancer (GC) is the main cause of mortality by cancer in Colombia.
      Glutathione S-transferase (GST) enzymes are involved in the detoxification of
      many environmental carcinogens. The homozygous deletions of glutathione S
      transferase M1 (GSTM1-0) and glutathione S-transferase T1 (GSTT1-0) have been
      associated with several types of cancer. The risk to develop GC has been
      associated with environmental factors and Helicobacter pylori infection. The
      tumor necrosis factor (TNF-alpha) and its levels are increased in patients
      infected with H. pylori. A G/ A transition in the position -308 of the promoter
      of the TNF-alpha has been related in several studies to an increased expression
      of the gene and is associated with susceptibility to GC. The association of these
      polymorphisms with GC and the interaction with other risk factors (life style)
      were investigated. Blood samples were obtained from 46 GC patients and 96
      controls. The logistic regression model was used to obtain the odds ratio (OR)
      and their 95% confidence intervals. These statistics established the association
      between the enzymatic polymorphisms and GC and between other independent factors
      and GC. The frequency of the TNF-alpha polymorphism in people infected with H.
      pylori was 18% in the GC population and 7% in the control group. This transition
      was not significantly associated with H. pylori infection and GC. The frequencies
      of the deletion polymorphisms for patients and controls were as follows: GSTM1
      65.2% and 37.5%; GSTT1 17.4% and 14.6%. These results suggested that the GSTM1
      deletion polymorphism was associated with an increased risk of gastric cancer (OR
      of 5.5; 95%CI, 1.7-17.2). Furthermore, other risk factors such as H. pylori
      infection (OR 5.58, CI 1.8-17.2), smoking (OR 6.70, CI 2.2-20.3) and alcohol
      intake (OR 3.27, CI 1.1-9.4) were associated with GC.

PMID- 15495596
TI  - [Epstein-Barr virus presence in Colombian Hodgkin lymphoma cases and its relation
      to treatment response].
AB  - The role of Epstein-Barr virus as etiologic agent in Hodgkin lymphoma (HL)
      development has been supported by the detection of viral DNA in the Reed
      Sternberg cell in a subset of HL, and the high levels of latent membrane protein
      1 expression in these tumors. To gain further evidence of this relationship,
      lymph nodes from 67 patients with HL were analyzed for the presence of Epstein
      Barr virus using EBERs in situ hybridization and LMP-1 immunohistochemistry.
      Virus presence was related to histological subtype, patients' treatment response
      and tumor infiltrating lymphocytes phenotype. EBERs transcripts were found in 67%
      of the cases and LMP-1 in the Reed-Sternberg tumor cells at a 56.7% rate. The
      prevalence, as determined by histological subtype, was 69.81% for nodular
      sclerosing, 85.71% for mixed cellularity and 40% for lymphocyte-rich. Epstein
      Barr virus presence was more frequent in children (84.2%) in comparison with
      adults (60.4%). Positive patients presented higher failure-free survival rates
      than Epstein-Barr virus negative patients. CD4 positive infiltrating T cells were
      present in a higher proportion in relation to CD8 positive T infiltrating cells,
      the mean percentages for both subsets were higher in Epstein-Barr virus positive
      cases. A high percentage of Epstein-Barr virus was present in HL with a probable
      association with treatment response. This suggests an application of Epstein-Barr
      virus detection to use as a prognosis marker in treatment response for HL cases.

PMID- 15495597
TI  - Incomplete surveillance of a dengue-2 epidemic in Ibague, Colombia, 1995-1997.
AB  - From April 1995 through November 1997 a dengue epidemic occurred in Ibague
      (400,000 population), Colombia, where 3,419 cases were reported and DEN 2 virus
      was isolated from seven patients. A sero-survey conducted in 1996 found evidence
      of previous dengue infection in 9.6% of the population, indicating that many
      infections had not been reported. The dengue infections occurred in all age
      groups, but children under five years of age were most frequently infected. Forty
      five percent of this Ibague population were born after the re-appearance of
      dengue in Colombia in 1972, but have never been infected with dengue virus. Most
      of the cases reported as dengue hemorrhagic fever did not fulfill the current
      case definition. Aedes aegypti larvae were found in 19% of dwellings surveyed,
      most often in uncovered low tanks used for water storage. Many residents were not
      acquainted with the domestic nature of the mosquito vector. Health workers
      attributed the failure of the dengue control programs to lack of leadership and
      other administrative problems.

PMID- 15495598
TI  - Degeneration of primary afferent terminals following brachial plexus extensive
      avulsion injury in rats.
AB  - Important breakthroughs in the understanding regeneration failure in an injured
      CNS have been made by studies of primary afferent neurons. Dorsal rhizotomy has
      provided an experimental model of brachial plexus (BP) avulsion. This is an
      injury in which the central branches of primary afferents are disrupted at their
      point of entry into the spinal cord, bringing motor and sensory dysfunction to
      the upper limbs. In the present work, the central axonal organization of primary
      afferents was examined in control (without lesion) adult Wistar rats and in rats
      subjected to a C3-T3 rhizotomy. Specific sensory axon subtypes were recognized by
      application of antibodies to the calcitonin gene-related peptide (CGRP), the P2X3
      purinoreceptor, the low-affinity p75-neurotrophin receptor and the retrograde
      tracer cholera toxin subunit beta (TCbeta). Other subtypes weres labeled with the
      lectin Griffonia simplicifolia 1B4. Using immunohistochemistry and high
      resolution light microscopy, brachial plexus rhizotomy in adult rats has proven a
      reliable model for several neural deficits in humans. This lesion produced
      different degrees of terminal degeneration in the several types of primary
      afferents which define sub-populations of sensitive neurons. Between the C6 and
      C8 levels of the spinal cord,, deafferentation was partial for peptidergic GCRP
      positive fibers, in contrast with elimination of non peptidergic and myelinated
      fibers. Dorsal rhizotomy has provided an adequate experimental model to study
      sensory alterations such as acute pain and allodynia as well as factors that
      affect regeneration into the CNS., Therefore, the differential deafferentation
      response must be considered inr the evaluation of therapies for nociception
      (pain) and regeneration for brachial plexus avulsion. The anatomical diffierences
      among the primary afferent subtypes also affect their roles in normal and damaged
      conditions.

PMID- 15495599
TI  - [Development and evaluation of a PCR method for diagnosis of Salmonella enteric
      fever, based on DNA sequences of the hilA gene].
AB  - Typically, diagnosis of enteric fever due to Salmonella spp. is by bacterial
      isolation from blood culture; however, the blood culture method is slow, not
      always available, and not informative in patients with antibiotic treatment.
      Salmonella spp. uses the hilA gene (component of the pathogenicity island I) to
      invade epithelial cells and produce infection. Using the hilA gene sequence a PCR
      test was designed to detect Salmonella in blood samples. The sensitivity (S),
      specificity (SP), positive predictive value (PPV) and negative predictive value
      (NPV) of the PCR method were obtained by testing the blood samples from 34
      patients with suspected of enteric fever. Presence of S. typhi was confirmed by
      blood culture. Blood samples were also tested from 35 patients with infections
      due to other non-Salmonella pathogens, again corroborated by blood culture
      (Klebsiella pneumoniae, 9; Serratia marcescens, 5; Escherichia coli, 4;
      Pseudomonas aeruginosa, 9; Providencia alcalifaciens, 4; Enterobacter cloacae,
      4). Control samples were obtained from 150 healthy volunteers. The S, SP, PPV and
      NPV for the PCR method were all 100%. The lowest number of colony forming
      units/ml detected by PCR in blood samples was 10.

PMID- 15495600
TI  - [Chromosomal localization of the KMP-11 genes in the KP1(+) and KP1(-) strains of
      Trypanosoma rangeli].
AB  - Genes encoding for the KMP-11 protein were localized on the chromosomes of
      Trypanosoma rangeli. These genes were located in two chromosomes of 3,100 and
      3,400 kb in the KP1(-) strain whereas in the KP1(+) H14 and Choachi strains, the
      genes are located in a chromosome of 1,600 kb. The Choachi strain presents an
      additional band of 1,400 kb. In the Shubacbarina and Munanta strains of
      Trypanosoma cruzi, the KMP-11 genes are located on a chromosomal band of 1,490
      kb. Therefore, the chromosomal localization of the KMP-11 genes presents a
      potential tool to differentiate among these parasites.

PMID- 15495602
TI  - [Genetics of preeclampsia: an approach to genetic linkage studies].
AB  - Due to its high prevalence during pregnancies, preeclampsia is considered an
      important public health problem. Many investigators agree in that its expression
      is related to the interaction between genetic and environmental factors. Many
      studies have searched for genetic factors, attempting to identify chromosomal
      regions or candidate genes whose variants may be related to high preeclampsia
      susceptibility. Several studies have associated a number of susceptibility genes
      to preeclampsia, but the results have not been replicated consistently in all
      populations. Mapping of genes and chromosomal regions by linkage analysis has
      located potential markers on chromosomes 2 and 4. Identification of the genes
      located in these candidate regions will pinpoint the genetic risk factors, will
      lead to a better understanding of the syndrome, and will provide clues for its
      prevention and treatment.

PMID- 15495603
TI  - [Experience of application of the mixed enteral preparation Peptamen after
      performance of radical operations for malignant gastroduodenal tumor].
AB  - Results of application of nutritional mixture Peptamen (Nestle, Switzerland) in
      the early period after performance of radical operations for gastroduodenal tumor
      were summarized. Application of balanced nutritional mixtures in complex of
      treatment of the patients permits to restore the gut content passage and,
      accordingly, to transverse them toward complete enteral feeding more early. The
      conversion of catabolic processes into anabolic occurs faster. In the patients,
      to whom the balanced nutritional mixtures were administered, the leucocytes
      formula had normalized more quickly, witnessing faster restoration of the
      organism immune system. Using enteral nutritional mixtures the hemodynamic and
      allergic complications do not occur. Economic expediency of the mixtures for
      enteral nutrition application was noted, because their cost is lower than that of
      the complete parenteral feeding in 3-5 times.

PMID- 15495604
TI  - [Content and molecular composition of circulating immune complexes in patients
      with multiple gastroduodenal ulcers].
AB  - In 45 patients with multiple gastroduodenal ulcers the humoral immunity indexes
      were studied up. Formation of secondary immune deficiency with simultaneous
      raising of the circulating immune complexes level on account of accumulation in
      the blood of their most pathogenic middle and small molecular fractions and
      reduction of large molecular fractions was established in patients with multiple
      gastroduodenal ulcers.

PMID- 15495605
TI  - [Comparative estimation of an acute gastroduodenal ulcers, complicated by
      hemorrhage according to indexes of enzymatic-biochemical spectrum of the blood].
AB  - Comparative estimation of methods of endoscopic hemostasis and treatment of an
      acute gastroduodenal ulcers, complicated by hemorrhage, was done: in 22 patients
      the conventional methods were applied, in 41-endoscopic hemostasis, using
      flatorization with the help of ozone-oxygen mixture and subsequent ozone
      insufflations. For the treatment efficacy control the endoscopic monitoring was
      used, there were studied cytobiochemical indexes of the dehydrogenases complex
      activity and of peroxide oxygenation of lipids. It was established, that
      ozonotherapy, even applied solely, guarantees the erosions healing in 3 days on
      average with simultaneous approximation to the norm of cytobiochemical indexes
      investigated.

PMID- 15495606
TI  - [Ultrasonic diagnosis of an acute appendicitis and its complications].
AB  - Retrospective analysis of the examination results in 292 patients with an acute
      appendicitis (AA) was conducted. There were 184 (63%) of patients operated on,
      for AA--168 (57.5%). Possibilities of ultrasonic investigation in the AA
      diagnosis were estimated. Due to introduction of this method it become possible
      to escape the operation performance in 58 (13.7%) of patients and to reduce the
      frequency of idle appendectomy for simple AA as twice. Broad application of
      ultrasonic investigation in urgent surgery would permit to establish the AA
      diagnosis correctly and substantially and to determine the tactic of patients
      treatment.

PMID- 15495607
TI  - [The application experience of Relief and Relief Advance in practice of the
      coloproctological patients treatment].
AB  - The application efficacy of Relief and Relief Advance preparations, as
      pathogenetically directed remedies, was established, basing on the examination
      and treatment results of 129 patients with anorectal zone diseases (acute and
      chronic hemorrhoids, anal fissure, the perianal skin pruritus, nonspecific
      ulcerative colitis, Crohn's disease). For local conservative treatment it is
      expedient to apply the complex of various pharmacological forms of the
      preparation. Combined application of Relief and Relief Advance preparations
      endorectally and locally on the wound surface is indicated after performance of
      elective and urgent operative interventions for rectal and perianal region
      diseases.

PMID- 15495608
TI  - [Clinical-diagnostic estimation of carbohydrates metabolism in obturation
      jaundice].
AB  - Complex examination of 175 patients with obturation jaundice was conducted,
      peculiar attention was spared to the carbohydrates metabolism changes,
      characterizing hepatic state. It was established, that in obturation jaundice in
      the liver there are occurring inflammatory changes and disturbances of all kinds
      of metabolism, including that of carbohydrates, severity of which depends on
      duration of jaundice, the concurrent diseases presence, they shows lowering of
      the glucose and glycogen level in the blood, as well as the hepatic glycogen
      content, that's why they may be applied as a complex of prognostic criterions for
      the disease course. An early conduction of operative treatment, elimination of
      the biliary ducts impassability promote the rehabilitation period shortening and
      the hepatic functional activity normalization.

PMID- 15495609
TI  - [Dynamic of nonspecific markers of endogenous intoxication under the influence of
      enteral probe nutrition in patients with choledocholithiasis].
AB  - Results of the dynamic investigation of the endogenous intoxication nonspecific
      markers in 107 patients suffering choledocholithiasis were presented. Under the
      influence of enteral probe nutrition, using oligosized mixture Peptamen (Nestle),
      in patients of the main group the endogenous intoxication nonspecific markers
      normalization had occurred faster than in a control group.

PMID- 15495610
TI  - [Peculiarities of occurrence and prophylaxis of pulmonary thromboembolism in an
      urgent abdominal surgery].
AB  - Results of treatment of 8146 patients with an acute disease and injury of the
      abdominal cavity organs, ageing from 15 to 93 years, were analyzed. Pulmonary
      thromboembolism (PTHE) had occurred in 47 (0.6%) of operated patients and in
      93.6% of observations have lead to exitus lethalis, in spite of reanimation
      measures and intensive therapy conduction. In 4.3% of patients the PTHE
      occurrence was preceded by clinical signs of the lower extremity deep veins
      thrombosis. The risk factors for the PTHE occurrence were adduced, coexistence of
      them was established in 44.2% of observations. Basing on comparative analysis of
      the fatal PTHE frequency, depending on the occurrence risk degree, the escalating
      of the PTHE risk in conditions of urgent abdominal surgery was substantiated. The
      probable efficacy of Fraxiparine in the PTHE prophylaxis was established.

PMID- 15495611
TI  - [The lower extremity amputation in vascular diseases].
AB  - There were examined 78 patients, to whom the lower extremity amputation on the
      hip level was performed. Complex examination, using the nuclear magnet resonance
      relaxation and arteriography, was performed. Introduction of method of the lower
      extremity amputation on the hip level, the apparatuses for the cutaneo-fascial
      flaps cutting out had permitted to reduce the purulent-septic complications
      frequency from 34.1 down to 7.8% and postoperative mortality--from 13.1 to 5.3%.

PMID- 15495612
TI  - [The operative activity factors in hospital clinics and surgical departments and
      variants of their solution].
AB  - There were investigated the causes, influencing operative activity in hospital
      clinics and surgical stationaries. The operative activity limitations were
      influenced by factor of the organization-management tactics, equally with the
      patients state severity, determined by surgical disease strictly and the presence
      of concurrent diseases of cardiovascular and respiratory systems. It was
      established, that to almost 50% of patients with an acute surgical disease the
      special cardiological examination is indicated, what demands to change the bed
      fund specialization and to standardize the surgical service volume in regional
      hospitals. In 28.4% of observations the surgical treatment is not conducted
      without objective substantiation, causing the patients quantity increase,
      suffering severe polyorgan diseases.

PMID- 15495613
TI  - [Optimization of surgical and reanimation tactic in injured persons with
      dominating damage of the abdominal cavity organs in polytrauma].
AB  - Results of surgical treatment of 148 injured persons with polytrauma in
      dominating damage of the abdominal cavity organs and concurrent damage of various
      anatomic-functional regions were analyzed. Taking into account the delineated
      reanimation-operative period there were presented surgical and reanimation
      tactic, intensive infusion-transfusion therapy in an acute massive blood loss,
      which was conducted in conditions of artificial pulmonary ventilation and general
      multicomponent anesthesy performed. Introduction of the tactic elaborated into
      the clinical practice had promoted significant improvement of the treatment
      results in injured persons with polytrauma.

PMID- 15495614
TI  - [A new method of performance of thoracic sympathectomy, based on the analysis of
      peculiarities of anatomical architecture of cervicothoracic sympathetic stem].
AB  - Peculiarities of anatomic structure (disposition, form, size) of stellate
      ganglion, II and III thoracic sympathetic ganglions together with their branches
      were suggested. There were established their morphological differences.
      Peculiarities of anatomical structure of the "lateral branch" II sympathetic
      ganglions were studied, its role in occurrence of the disease recurrence after
      performance of the thoracic sympathectomy performance was proved. Basing on the
      results achieved the method of thoracoscopic sympathectomy performance for
      Raynaud's phenomenon was elaborated.

PMID- 15495615
TI  - [Experience of surgical treatment of diffuse thyrotoxic goiter in children and
      teenagers].
AB  - Results of surgical treatment of 137 children, operated on for thyrotoxic goiter
      (TG) in 1989-2002 yrs were analyzed. Thyrotoxic ophthalmopathy was revealed in 86
      (62.7%) patients, papillary carcinoma on background of diffuse TG--in 3 (2.1%).
      Subtotal resection of thyroid gland according to O. V. Nikolayev was performed in
      99 (72.2%) patients, almost thyroidectomy--in 30 (21.8%), thyroidectomy--in 8
      (5.8%). All the patients are alive. Bilateral affection of nervus laryngeus
      recurrens was not observed. Unilateral injury of nervus laryngeus recurrens was
      revealed in 5 (3.6%) childs. Transient hypoparathyrosis was noted in 20 (14.5%)
      patients. The TG recurrence had occurred in 5 (3.6%) childs, postoperative
      hypothyrosis--in 100 (72.9%).

PMID- 15495616
TI  - [Application of immunomodulators for correction of changes in the immune system
      in conditions of experimental hypothyroidism].
AB  - Changes of the immune system state were investigated in mice after performance of
      thyroidectomy under the influence of hormonal therapy using thyroxin and
      immunotropic preparations thymogen and polyoxydonium. In hypothyrosis there was
      observed the trustworthy lowering of the thymus endocrine function, interleukine
      2 activity, cytotoxic activity in the physiological cell-killers, the leukocytes
      proliferating ability and increase of the blood content of circulating immune
      complexes as well. The restorational therapy conduction using thyroxin,
      injections of thymogen or polyoxydonium removed the above mentioned changes only
      in part. The immunomodulators application, under condition of the hypothyrosis
      compensation occurrence, have had promoted the essential raising of their
      therapeutic action and secured the immune state restoration after thyroidectomy
      performance.

PMID- 15495617
TI  - [Role of interrelationship of neutrophils, endotheliocytes and mononuclear
      macrophages in occurrence and course of purulent-septic state. Communication 5.
      Mechanisms of kinetics of neutrophyl].

PMID- 15495618
TI  - [Foreign body of abdominal cavity as a cause of the complications occurrence].

PMID- 15495619
TI  - [Experience of median-linking laparotomy in abdominal surgery].

PMID- 15495620
TI  - [Operative interventions for the burn and cicatricial esophageal stenosis along
      the stages before the plasty].

PMID- 15495621
TI  - [Rare observation of diaphragmatic hernia].

PMID- 15495622
TI  - [Meckel's diverticulum as a cause of an acute adhesional ileus].

PMID- 15495623
TI  - [Posttraumatic laceration of hepatic solitary cyst].

PMID- 15495624
TI  - [Atypical clinical course of giant pulmonary tuberculoma].

PMID- 15495625
TI  - [Prophylaxis for the purulent complications occurrence in healing of primarily
      infected wound].

PMID- 15495626
TI  - Consumer-driven health plans are rapidly being added by the country's largest
      insurers and managed care organizations.

PMID- 15495627
TI  - Medicaid managed care: there's more for states to do.
AB  - Medicaid is a cornerstone of this country's health care system, covering over 50
      million people and supplying one in five health care dollars in the United
      States. Medicaid is again a contested issue in state capitols, where states
      facing sluggish revenues target Medicaid since it is the second largest and
      fastest growing component of state spending. Managed care was the policy tool
      many states embraced in order to slow Medicaid spending, and while managed care
      has had some successes in improving Medicaid services, it has not met states'
      expectations for cost savings. This analysis explores several reasons why these
      savings have not been realized, and proposes policy reforms for state Medicaid
      programs that would make Medicaid coverage more stable, thereby increasing the
      ability of managed care plans and network providers to work with Medicaid
      beneficiaries to change patterns of care and realize real savings.

PMID- 15495628
TI  - A marketing solution: managed care woes?
AB  - Two interrelated problems are included among the causes of managed care woes: the
      dramatic increase in unhealthy lifestyles together with the results these have
      had on health services utilization and expenditures; and the dramatic increase in
      consumer demand for "lifestyle" or quality of life (QoL) enhancing products and
      services. Together these are helping to drive managed care toward a crisis, in
      both commercial and government-sponsored insurance survival prospects. Aside from
      the frequently mentioned problem of our aging population and the shifting balance
      between the number of healthy young workers paying in, vs. unhealthy or older
      workers spending out, these problems greatly exacerbate the double-digit
      inflation that has become a recurring characteristic of health insurance
      premiums, and threaten the very existence of managed care.

PMID- 15495629
TI  - The truth about managed care: the silent provider discount.
AB  - At a time when many managed care organizations (MCOs) have announced improvements
      in administrative systems and a desire to ease provider relations and pay
      providers correctly and timely, many physician organizations continue to
      experience great difficulty in obtaining prompt and accurate claims payment. To
      understand this phenomenon better, physician organizations at two leading
      academic medical centers in the Northeast and South, respectively, compiled an
      analysis of their recent managed care claims payment experience. This analysis
      revealed substantial underpayments from MCOs, and documented the added
      administrative expense required to recover such underpayments.

PMID- 15495630
TI  - Financial performance indicators for health plans in Medicaid managed care.
AB  - This study is a descriptive analysis of the financial performance of licensed
      managed care plans that participate in Medicaid by ownership, provider
      sponsorship, and the level of Medicaid focus and Medicaid enrollment. Using 2001
      Interstudy data, health plan financial data for the Medicaid product line are
      analyzed on a national level for individual plans. Using SEC 10-K financial
      filings, company level analysis of two publicly traded, Medicaid-focused, managed
      care plans are analyzed as well. The analysis found that for-profit and non
      profit plans had similar profit margins; however, for-profit plans incurred
      higher administrative costs ratios and lower medical benefits ratio. Plans with
      higher Medicaid enrollment had higher medical benefits ratios, while both
      provider-sponsored and non-provider sponsored plans had similar profit margins.
      Finally, publicly traded Medicaid focused plans achieved profit margins
      considerably higher than other Medicaid-focused plans.

PMID- 15495631
TI  - What health plans report. And don't report.

PMID- 15495632
TI  - [Read me information for authors].

PMID- 15495633
TI  - [Clinical assessment of a new anesthetic system: the Temel Supra (II)].
AB  - OBJECTIVES: To assess the clinical performance of a new anesthetic system
      developed to provide novel advantages in ventilating the anesthetized patient.
      PATIENTS AND METHOD: The clinical performance of the Temel Supra was evaluated in
      100 adult patients who were anesthetized and ventilated using the device.
      RESULTS: The patients were adequately oxygenated and ventilated; no adverse
      events were observed. An open circuit, low flow, or closed circuit could be
      chosen freely. Ventilation was fully monitored: among the variables measured were
      rebreathed volume; leaks while the patient was connected; consumption of oxygen,
      nitrous oxide and anesthetic agents; and cardiac output (noninvasively).
      CONCLUSIONS: Ventilation and gas exchange were satisfactory in all cases even
      though some patients developed considerable respiratory impedance. The monitoring
      of oxygen and other gases consumed and of carbon dioxide produced provided very
      valuable information about metabolism and pharmacokinetics. The noninvasive
      monitoring of cardiac output seems to us to be a useful feature for aiding
      hemodynamic control. The independence of the open and closed circuits means that
      expired gases do not pass through the canister when the open circuit is used,
      resulting in savings on soda lime for drying. During pressure-control
      ventilation, the system maintains a plateau to guarantee better distribution of
      inspired gases. Other important features are warnings, constant monitoring of
      leaks, the 100% efficacy of the circuit, and the low internal volume.

PMID- 15495634
TI  - [Intraoperative measurement of cardiac output by transesophageal echocardiography
      of transmitral flow].
AB  - INTRODUCTION: Intraoperative transesophageal echocardiography is used to study
      cardiac structure and function. Cardiac output is measured by calculating the
      velocity with which a volume of blood travels a predetermined area. Output can be
      assessed at the mitral valve by parallel alignment of the Doppler transducer to
      measure flow velocity. OBJECTIVE: To compare cardiac output measurements from
      transesophageal echocardiography with measurements performed by the standard
      clinical technique of thermodilution. PATIENTS AND METHODS: Cardiac output
      measurements obtained by thermodilution and by echocardiography at the mitral
      valve were compared in a prospective study during 34 cardiac surgery procedures.
      RESULTS: Cardiac output measurements ranged from 2.3 L min(-1) to 7.8 L min(-1)
      (mean 4.27 +/- 0.125 L min(-1) for measurements made by Doppler echocardiography
      and from 1.9 L min(-1) to 8.1 L min(-1) (mean 4.36 +/- 0.124 L min(-1)) for
      measurements made by thermodilution. The correlation between the methods was high
      (r = 0.926, p = 0.00001). CONCLUSION: Intraoperative measurement of cardiac
      output by transesophageal Doppler echocardiography at the mitral valve is easy
      and correlates highly with the clinical method of thermodilution used at present.
      Use of the technique will widen the spectrum of information provided by
      echocardiography, which is a safe, minimally invasive technique.

PMID- 15495635
TI  - [Rocuronium: onset time or speed of action?].
AB  - OBJECTIVE: Rocuronium has been said to have an initially rapid onset of action
      followed by a slower final approach to maximum effect, the supporting data
      showing only that time to 75% of blockade is more rapid. Expressions of velocity
      are derived from basic measures such as length and time. The aim of our study was
      to confirm the onset characteristics of rocuronium by using appropriate
      expressions of velocity. PATIENTS AND METHODS: After consenting, 25 adults
      scheduled for elective surgery were anesthetized, using a bolus dose of
      rocuronium of 400 microg Kg(-1) for relaxation. Electromyography was used to
      determine maximal effect, time to reach 80% of a full neuromuscular block, onset
      time, the time interval between these two points, and the differential blockade
      produced during each period. Velocity for each period was calculated as the ratio
      between the percentage of block produced per amount of time elapsed (%/s) during
      each respective period. The ratio between time and blockade (s/%) was also
      calculated. RESULTS: More blockade was produced per second (velocity) during the
      initial period of activity (0.55%/s) than during the final period (0.109%/s). The
      average velocity during the onset period overall (0.33%/s) lay between those two
      figures. Rocuronium requires less time (acting fast) to achieve an initial effect
      (1.95 s/%) than it does to reach the final effect (10.8 s/%). The ratio of early
      to late speed of onset was 5.8 +/- 3.5. CONCLUSION: Using appropriate expressions
      and calculations, we can unequivocally conclude that rocuronium has a biphasic
      onset that is initially rapid and then slower. The rate of action is nearly 6
      times faster at the beginning.

PMID- 15495636
TI  - [Obstetric analgesia in 28 women with idiopathic thrombocytopenic purpura].
AB  - OBJECTIVE: To assess complications arising from regional analgesia for obstetric
      labor and delivery in women with idiopathic thrombocytopenic purpura (ITP).
      MATERIAL AND METHODS: Retrospective study of case records of women with ITP who
      gave birth at our hospital over the 10-year period from 1993 through 2002.
      Quality control checklists were applied to case records before including them for
      study. The chart had to contain information on the type of analgesia/anesthesia
      used during labor or cesarean section, the results of complete peripartum
      coagulation tests, and a record of the presence or absence of anesthetic
      complications. Twenty-eight births involving 24 patients with ITP were studied.
      RESULTS: Regional analgesia/anesthesia, usually by epidural infusion, was the
      technique most often used. All patients had prothrombin and cephalin times within
      the normal ranges. Regional analgesia/anesthesia was never used in cases where
      the platelet count was less than 70,000/mm3. In such cases, general anesthesia
      was used for cesareans, with endovenous administration of opioids. No analgesia
      was used when the patient declined it for normal deliveries. Eleven cesarean
      deliveries and 17 vaginal deliveries were recorded. No complications were
      observed either with regional or endovenous techniques. CONCLUSIONS: The regional
      neuroaxial techniques used in this series of women with ITP, in whom platelet
      counts exceeded 70,000/mm3, were not associated with hemorrhagic complications.

PMID- 15495637
TI  - [Four patients with mucormycosis in a postoperative recovery unit].
AB  - Mucormycosis, a rare opportunistic infection caused by fungi belonging to the
      Mucorales order, is a potentially fatal disease. We describe 4 patients with
      mucormycosis. Risk factors (chronic renal insufficiency and chronic lung disease
      treated with corticosteroids) were identified for 2 of the patients who did not
      respond favorably to appropriate surgical and medical treatment. Of the 2
      remaining patients, only the one with milder disease responded to treatment. The
      prognosis for this opportunistic infection, whose low incidence has increased in
      postoperative intensive care units, is very poor if early treatment is not given.

PMID- 15495638
TI  - [Lazarus phenomenon: spontaneous resuscitation].
AB  - A 94-year-old woman undergoing surgery for simple repair of a duodenal
      perforation experienced a sudden massive hemorrhage (1500 mL) when the duodenum
      was separated from adjacent structures. Hemodynamic stability was re-established
      when fluids were replaced. After the abdominal wall was closed, increased
      amplitude of the QRS wave was observed and heart rate slowed until there was no
      pulse. Electromechanical dissociation (EMD) was diagnosed and cardiopulmonary
      resuscitation was started. When EMD persisted after 40 minutes, resuscitative
      measures were stopped and the ventilator was disconnected, though orotracheal
      intubation and arterial and electrocardiographic monitoring were maintained.
      After 2 or 3 minutes, heart rhythm restarted spontaneously and arterial pressure
      waves reappeared on the monitor. The patient progressed well for 72 hours, after
      which she developed septic shock and multiorgan failure, dying 18 days later. The
      Lazarus phenomenon may be more common than the medical literature would indicate,
      possibly because a large gap in our understanding of the pathophysiology of the
      phenomenon underlies anecdotes about "miracles". As we wait for adequate
      international consensus on a protocol for monitoring the withdrawal of
      resuscitative measures, we should act prudently before definitively certifying
      death. The case we report occurred during a surgical intervention in which the
      patient had received general anesthesia. We believe that the causes that might
      explain the Lazarus phenomenon are quite different in that context than they
      would be in a nonsurgical setting, such that it would be useful to create a
      national database to keep a record of such intraoperative events.

PMID- 15495639
TI  - [Anaphylactic reaction versus carcinoid crisis: the role of octreotide as a
      vasoconstrictor].
AB  - A 35-year-old woman was scheduled for laparoscopic removal of an ovarian tumor.
      Intravenous metamizol was administered and when pneumoperitoneum was performed
      she developed severe hypotension and bronchospasm. Anaphylactic reaction was
      suspected, all drugs were suspended, and 2 doses of intravenous adrenalin (0.2
      and 1 mg) were injected followed by continuous perfusion. Because response was
      slow and given the unknown origin of the tumor, the possibility of a carcinoid
      crisis was considered. When an intravenous bolus dose of octreotide was
      administered, pressure recovered, patient was extubated and could be transferred
      asymptomatic to the recovery ward. Tests later ruled out carcinoid syndrome,
      whereas tryptase levels in blood extracted during surgery and allergy tests
      confirmed an anaphylactic reaction to metamizol. Carcinoid crisis can be
      difficult to distinguish from anaphylactic reaction because the clinical pictures
      are similar. Anesthetic management of carcinoid crisis has been facilitated by
      administration of octreotide. Less is known about the use of octreotide to treat
      hypotension in patients with autonomic neuropathy based mainly on the drug's
      ability to produce splanchnic vasoconstriction. This is probably the reason why
      octreotide resolved our patient's shock in a context of systemic vasodilation
      caused by the anaphylactic reaction.

PMID- 15495640
TI  - [Noncardiogenic pulmonary edema and acute kidney failure after withdrawal of a
      central venous catheter].
AB  - A 17-year-old male suffered severe noncardiogenic pulmonary edema with arterial
      hypotension and acute renal insufficiency after withdrawal of a central venous
      catheter from the subclavian vein. The patient was in semirecumbent supine
      position with the head of the bed at a 40 degree angle. Resuscitation maneuvers,
      orotracheal intubation, and hemodynamic support were required. After 4 days in
      intensive care the patient had fully recovered. Fibrin tracts form around
      catheters and can create a way for air to enter a vein after catheter removal.
      The causes of pulmonary edema secondary to venous air embolism have been well
      studied: it seems that edema develops as a consequence of the sudden appearance
      of small air bubbles in pulmonary circulation, leading to an acute inflammatory
      response in pulmonary microvasculature. Experimental studies have shown that
      edema is associated with increased pulmonary vascular resistance that leads to
      pulmonary hypertension. Venous air embolism as a complication of central venous
      catheterization is too seldom detected and little stress is placed on this
      possibility in the care and removal of catheters.

PMID- 15495642
TI  - [Obstetric epidural analgesia in a case of spinal bifida occulta].

PMID- 15495641
TI  - [Caudal block and sedation for bilateral herniorrhaphy in an infant with Cornelia
      de Lange syndrome].

PMID- 15495643
TI  - [Usefulness of pulse oximetry for the early diagnosis of postoperative arterial
      occlusion after placement of a hip prosthesis].

PMID- 15495644
TI  - [Anaphylactic reaction to propofol and beta-lactam antibiotics].

PMID- 15495645
TI  - [Cardiac arrest during a cesarean section with spinal anesthesia].

PMID- 15495646
TI  - [Turbinate avulsion: history repeats itself].

PMID- 15495647
TI  - [Is allergy to nonsteroidal antiinflamatory drugs common in surgical patients?].

PMID- 15495648
TI  - [Comment on the letter "Spinal anesthesia and tattos"].

PMID- 15495649
TI  - [Landmark events in European anesthesiology].

PMID- 15495650
TI  - William George Cross, MBBS, MS, BA, LDS RCS, MRCS, LRCP, FDS: the influence of
      America.

PMID- 15495651
TI  - Sir Wilfred Fish.

PMID- 15495652
TI  - History of dental surgery at Buchenwald (1937-45): witnesses, archives,
      statistics.

PMID- 15495653
TI  - 'Sequah': crown prince of charlatans.

PMID- 15495654
TI  - Fishburn: Malta's first dental graduate.

PMID- 15495655
TI  - Martin Rushton, CBE, LLD, MD, OdontD, FRCS, FDS: an appreciation.

PMID- 15495657
TI  - Taking stock of science in the schoolhouse: four ideas to foster effective
      instruction.
AB  - In the opening discussion of this special issue, I take stock of science and
      schooling for students with learning disabilities (LD) before probing four ideas
      to foster effective instruction in contemporary schools: (a) Turn to science as
      the best trick we know for solving educational problems; (b) specify clearly what
      we hope to achieve in our instructional decisions for students with LD; (c) rely
      on instruction as the best tool we have for improving student performance; and
      (d) cultivate-and keep-competent and caring personnel. I invite commentary, from
      the perspectives of researchers, practitioners, and those who prepare teachers
      and administrators, to assess the status of science in the schoolhouse and to
      offer practical strategies for how the scientific orientation of schools might be
      enhanced.

PMID- 15495658
TI  - Scientific practice and the tradition of advocacy in special education.
AB  - The purpose of this discussion is to describe and contrast several tenets of
      scientific behavior and practice with the behaviors and practices associated with
      advocacy. We argue that scientists must focus their efforts on solvable problems,
      consider their efforts to be uncertain, and present their findings
      dispassionately, so that others might judge the evidence for themselves.
      Advocates, in contrast, must confront the problems facing the people for whom
      they have concern over whether the problems appear to be solvable or not.
      Furthermore, advocacy requires a certainty of conviction that leads to the
      promotion of particular positions and their adoption by others. We suggest that
      although special education's roots are more closely aligned with advocacy than
      with science, its future depends on its ability to adopt a more fully scientific
      approach to practice. We conclude with a discussion of how the assignment of test
      accommodations to students with disabilities illustrates the tension between
      science and advocacy.

PMID- 15495659
TI  - Science in the schoolhouse: an uninvited guest.
AB  - Science and scientific thinking have not made a substantial impact on educational
      practice. In this discussion, we examine the relationship between science and
      education and delineate four reasons for characterizing science as an uninvited
      guest in schools: (a) Science is not highly regarded in society; (b) good science
      and bad science are often mistaken for one another; (c) the amount of current
      data is overwhelming; and (d) science is not easy for those who practice it
      (researchers), those who translate it (teacher educators), or those who consume
      it (teachers). We suggest several strategies to improve this relationship,
      including promoting standards of educational practice, emphasizing the role of
      teacher educators as translators of the research base into classroom practice,
      and linking student outcomes with the use of effective instructional practices.

PMID- 15495660
TI  - Maintaining the relationship between science and special education.
AB  - Science has been an important partner of the field of learning disabilities since
      its inception. Special educators have used science to confirm or reject
      approaches to identifying and teaching students with disabilities. Current
      research and practice is using science to find better approaches to preventing
      learning difficulties and reducing the number of students referred for special
      education. However, I caution that if we want science to have the desired impact
      on the educational and social outcomes of students with learning disabilities, we
      must take care not to misuse it.

PMID- 15495661
TI  - Co-teaching as science in the schoolhouse: more questions than answers.
AB  - The concept of science in the schoolhouse combines knowledge of research-based
      practices with the complexities of day-to-day life in schools. In this
      discussion, co-teaching is offered as an example of how advocacy for a practice
      can outpace the science that supports it. There is a push for co-teaching in
      contemporary schools, and special educators in great numbers are being asked to
      join with general educators in meeting the needs of students with disabilities.
      However, the science behind co-teaching to date is very limited. Studies have
      examined the implementation of co-teaching as a general service delivery option,
      but much less attention has been paid scientifically to the character and quality
      of the co-taught instruction or to the impact of co-teaching on student outcomes.
      Within this context, I also examine how Crockett's four recommendations to
      support science in the schoolhouse could address the questions about co-teaching
      for which there are few answers.

PMID- 15495662
TI  - Revealing the hidden world of research.
AB  - Bringing the science of schooling into standard practice for students with
      learning disabilities (LD) is a threefold process that requires understanding the
      nature and features of high-quality instruction, encouraging their use, and
      developing and maintaining systems that can sustain them. Examples are drawn from
      the LD research base to illustrate each of these areas, with a focus on research
      in reading acquisition with young children at risk of LD and with older students
      with LD. These examples suggest a continued push for special education reading
      instruction through and past the elementary years. I conclude with
      recommendations for preparing teachers that take advantage of the knowledge
      gained from research-to-practice endeavors across the country.

PMID- 15495663
TI  - Improving beginning reading instruction and intervention for students with LD:
      reconciling "all" with "each".
AB  - We begin with an examination of the tensions that exist between educational
      efforts that target the needs of all students and efforts that target the needs
      of individual students with disabilities. Next, we provide reasons why, in
      beginning reading, a schoolwide system designed to teach all students to read can
      also support individualized and flexible instruction designed to teach each
      student to read. Finally, we describe a schoolwide beginning reading model that
      includes a schoolwide framework or infrastructure that supports comprehensive and
      coordinated reading goals, assessment, and instruction for all students
      integrated with ongoing progress monitoring and instructional adjustments that
      allow for differentiated and individualized instruction for each student,
      including students with disabilities.

PMID- 15495664
TI  - Bringing science into the classroom by basing craft on research.
AB  - In response to Crockett's analysis of the relation of science and the instruction
      of students with learning disabilities, we discuss reasons why teaching in
      special education is infrequently affected by science and research, and we
      propose a model of naturalistic decision making and make recommendations for
      bridging the gap between research and practice based on that model. By building
      an extensive experiential base in using effective practices, we propose that
      teachers can become experts at the craft of applying research-based methods.
      Bringing science into the classroom by basing craft on research in this way
      represents one promising alternative for improving outcomes for students with and
      without learning disabilities.

PMID- 15495665
TI  - The science of professional development.
AB  - In this commentary, I discuss the science of professional development. A great
      deal is already known about how to provide professional development that supports
      teachers' implementation of evidence-based practices and the factors that enhance
      or inhibit teachers' sustained use of the practices. I summarize the work of
      researchers who have achieved some success in facilitating teachers' learning of
      new practices, highlighting my own research with colleagues. Professional
      development is known to be most successful when (a) researchers work closely with
      school districts, so that everyone is on the same page, and the practices that
      researchers are teaching are aligned with the district's curriculum and
      standards; (b) student outcome data showing that the practice works are provided
      to all; (c) administrative support is clearly evident; (d) long-term support is
      provided for teachers (including demonstrations and coaching); and (e) teachers
      take ownership of the practices and responsibility for mentoring their peers.

PMID- 15495666
TI  - Science in the schoolhouse: the critical role of the school leader.
AB  - School-level administrative support has been identified as an essential component
      of programs that promote research to practice. In this discussion, I address the
      critical role that school leaders play in supporting special educators and
      ensuring effective instruction for students with learning disabilities. Emphasis
      is placed on the need for teachers to be supported by administrators who are
      knowledgeable about special education and for administrators to receive the
      preparation and guidance they require to support science in contemporary schools.

PMID- 15495667
TI  - Transforming administration to support science in the schoolhouse for students
      with disabilities.
AB  - I examine the role that administrators play in facilitating the development,
      adoption, use, and evaluation of scientifically based interventions within the
      school culture to support the educational outcomes of students with learning
      disabilities (LD). Two ways of transforming the administrative role to support
      science in the schoolhouse are presented; one considers the importance of
      including language in future legislation that acknowledges the role of
      administrators in school reform, and the other focuses on establishing a national
      research agenda addressing issues of leadership and special education. I argue
      that these 2 venues should serve to identify and to stimulate the use of evidence
      based administrative practices that ultimately increase educational outcomes for
      students with LD, improve teacher instruction, and transform the leadership
      mission.

PMID- 15495669
TI  - Working out the workout.

PMID- 15495668
TI  - Science and schooling for students with LD: a discussion of the symposium.
AB  - In this summative discussion, we respond to Crockett's proposals about supporting
      science in the schoolhouse, and we summarize and reflect on the perspectives of
      the commentators. Overall, they identify discussion points in issues of science
      in schooling, implementation of scientific practices, teacher training and
      professional development, and issues in educational administration and
      leadership. We agree with Crockett and the commentators that intensive efforts in
      all these areas must be made to strengthen the role of science in the
      schoolhouse.

PMID- 15495670
TI  - Fitting in fitness.

PMID- 15495671
TI  - Mission possible.

PMID- 15495672
TI  - Behind Gate 27.

PMID- 15495673
TI  - Leading the fitness charge.

PMID- 15495674
TI  - Clearing the hurdles.

PMID- 15495675
TI  - Working wireless.

PMID- 15495676
TI  - Cardiovascular diseases and their prevention in Minnesota.
AB  - Despite Minnesota's good standing in national health rankings, preventable heart
      attacks and strokes continue to be a major medical, social, and economic burden.
      The recent downward trend in deaths from cardiovascular diseases (CVD) is now
      becoming less steep, and there has been an actual increase in stroke deaths.
      Moreover, average risk factor levels in the population are no longer decreasing,
      and health behaviors are deteriorating, particularly among youth and lower
      socioeconomic groups. This article reviews these Minnesota trends and outlines
      tested and promising medical and population wide approaches for reducing further
      the impact of CVD and for promoting health. These include self-help, school, work
      site, health provider, and community-based efforts.

PMID- 15495677
TI  - Raising awareness of hypertension among Minnesotans.

PMID- 15495678
TI  - Preventing cardiovascular disease in women: an intervention-control randomized
      study.
AB  - This 1-year, group-randomized, intervention-control study looked at the
      effectiveness of a primary prevention, community-based program for reducing
      cardiovascular (CV) risk factors in women. Women between the ages of 20 and 50
      were recruited through community contacts, including religious and academic
      institutions, health clinics, and large local employers in the Duluth, Minnesota,
      and Superior, Wisconsin, area. All study activities took place in neighborhood
      places of worship. Screenings at baseline and 12 months included physical and
      laboratory measurements addressing CV risk factors and assessment of the women's
      knowledge about CV disease in women. All participants received an individualized
      review of their CV risk factors and recommendations for modifying them, along
      with educational literature about CV disease in women. The control group had
      limited follow-up compared with the intervention group, who participated in
      general CV health classes and received a follow-up phone call and information
      about health resources. The study showed that education and one-on-one follow-up
      significantly change behavior. Comprehensive community-based screening and
      individualized review decrease women's risk for CV disease.

PMID- 15495680
TI  - Medical ethics guide physicians' actions.

PMID- 15495679
TI  - The role of flexibility in injury prevention and athletic performance: have we
      stretched the truth?
AB  - The use of stretching to prevent injury, off-set muscle soreness, and improve
      performance has been widely accepted and promoted in sports. However, little or
      no scientific evidence supports the practice, and recent research suggests that
      stretching, which increases flexibility beyond that needed for sport-specific
      movements, may cause injury. This article presents studies that have looked at
      the effects of stretching on injury and performance. Many earlier studies that
      showed benefits of stretching did not look at the effects of stretching alone;
      they also involved general cardiovascular workouts in the experimental but not
      control groups. More recent research shows that general fitness, rather than
      stretching, is a more important risk factor in injury prevention. This article
      also discusses studies of the relationship between joint laxity and injury and
      the role that stiffness may play in enhancing performance and preventing injury.
      Overall, the evidence suggests that increasing range of motion beyond function
      through stretching is not beneficial and can actually cause injury and decrease
      performance. These findings should be used to challenge common warm-up practices
      in athletics.

PMID- 15495681
TI  - [Treatment guidelines of acute poisoning in primary care setting].

PMID- 15495682
TI  - [The latest tendency of uncontrolled substance inquiries to JPIC].

PMID- 15495683
TI  - [MHLW's countermeasures for uncontrolled substance and future tasks].

PMID- 15495684
TI  - [Analysis of latest trends in illegal drug consumption ].

PMID- 15495685
TI  - [Latest cases of acute poisoning in clinical practice--5MeO-DIPT and GHB
      precursor].

PMID- 15495686
TI  - [Development of a simple method of detecting acetaminophen using 96 well
      microplate readers].
AB  - Acetaminophen (APAP: N-Acetyl-p-aminophenol) has been widely used as a relatively
      safe antipyretic and analgesic drug. However, APAP is known as a major causative
      agent of fulminant hepatic failure, in a dose and a blood concentration dependent
      manner, in Western countries. The APAP toxicity should be expected to increase in
      proportion as the increasing of the clinical use in Japan. Therefore, a
      simplified method which determines the concentration of APAP would be valuable
      for clinical use. We have modified the APAP determination method developed by
      Yasojima. Our method enabled to measure APAP concentration with a small volume of
      samples by using 96-well microtiter plate, which can handle multiple samples
      simultaneously. From 10 microg/ml to 320 microg/ml of APAP was quantitatively
      measured by our method, which is suitable for diagnostics of the APAP toxicity.
      APAP levels below the lethal concentration of 160 microg/ml can be determined
      with one plate.

PMID- 15495688
TI  - [Simple detection of arsenic compound using the Merckoquant Arsen-Test].

PMID- 15495687
TI  - [Three cases of organophosphate poisoning treated with pralidoxime iodide and
      whole-bowel irrigation].
AB  - We encountered three cases of organophosphate poisoning treated with pralidoxime
      iodide (PAM) and whole-bowel irrigation without atropine sulfate. All patients
      recovered without persistence or recurrence of toxic symptoms and without any
      somatic after effects. In case 1, a 48-year-old woman ingested approximately 5 g
      of ethylthiometon in a suicide attempt. She was transferred to the hospital
      because of cardiopulmonary arrest. After resuscitation, she was transferred to
      our center. She was placed on a ventilator and received i.v. PAM and polyethylene
      glycol-electrolyte through a nasojejunal tube for whole-bowel irrigation. Six
      days later, serum ChE was improved. In case 2, a 51-year-old man ingested
      approximately 30 g of malathion in a suicide attempt and was transferred to our
      center because of dyspnea. He was treated with PAM and whole-bowel irrigation,
      but did not require a respirator. Serum ChE already showed improvement the
      following day. In case 3, a 31-year-old man ingested approximately 50 g of DEP in
      a suicide attempt and was transferred to our center because of unconsciousness.
      He was treated with a respirator, PAM and whole-bowel irrigation. Serum ChE
      improved within two days. These cases suggest the possibility that preferential
      whole-bowel irrigation without atropine sulfate prevents the persistence or
      recurrence of the toxic effects of organophosphate.

PMID- 15495689
TI  - [Practical analysis of toxic substances useful for clinical toxicology-
      Methamphetamine].

PMID- 15495690
TI  - [Effective product labeling for prevention of poisoning--from the viewpoint of
      consumers].

PMID- 15495691
TI  - Wolff-Parkinson-White syndrome: essentials for the primary care nurse
      practitioner.
AB  - PURPOSE: To provide nurse practitioners with a basic understanding of the
      pathophysiology, clinical characteristics, diagnostic methods, and management of
      Wolff-Parkinson-White (WPW) syndrome. DATA SOURCES: Selected research and
      clinical articles. CONCLUSIONS: WPW syndrome is the most common form of
      ventricular preexcitation. The ventricular myocardium is activated earlier than
      expected by an accessory conduction pathway that allows a direct electrical
      connection between the atria and ventricles. Although many patients remain
      asymptomatic throughout their lives, approximately half of the patients with WPW
      syndrome experience symptoms secondary to tachyarrhythmias, such as paroxysmal
      supraventricular tachycardia, atrial fibrillation, atrial flutter, and, rarely,
      ventricular fibrillation and sudden death. Symptoms include palpitations,
      dizziness, syncope, and dyspnea. Diagnosis is usually made by electrocardiogram
      findings, but further testing may be warranted to confirm the diagnosis.
      IMPLICATIONS FOR PRACTICE: A thorough patient history and physical examination
      can aid the practitioner in identifying patients who may have WPW syndrome. With
      appropriate referral, treatment, and patient education, patients with WPW
      syndrome can expect to have a normal life expectancy and good quality of life.

PMID- 15495692
TI  - Treatment of hypertriglyceridemia with omega-3 fatty acids: a systematic review.
AB  - PURPOSE: To (a) critically appraise available randomized controlled trials (RCTs)
      addressing the efficacy of long-chain omega-3 fatty acids as secondary agents for
      prevention of hypertriglyceridemia and (b) make recommendations for clinical
      practice. DATA SOURCES: Two independent reviewers examined all RCTs from 1994 to
      2003 identified in several databases, extracted data from each study, and used
      the previously tested Boyack and Lookinland Methodological Quality Index (MQI) to
      determine study quality. CONCLUSIONS: Ten studies reported long-chain omega-3
      fatty acids to be effective in the treatment of hypertriglyceridemia. The average
      decrease in triglycerides was 29%, total cholesterol 11.6%, very low density
      lipoprotein (VLDL) 30.2%, and low-density lipoprotein (LDL) 32.5%. One study
      found LDLs to increase by 25%. The average increase in high-density lipoprotein
      was 10%. The overall average MQI score was 36% (range = 26% to 54%). Many of the
      RCTs had serious shortcomings, including short duration, lack of a power
      analysis, no intention-to-treat analysis, no report of blind assessment of
      outcome, and lack of dietary control as a confounding variable. IMPLICATIONS FOR
      PRACTICE: Overall study methodology was weak. Although the evidence supporting
      use of long-chain omega-3 fatty acids in the secondary prevention of
      hypertriglyceridemia is reasonably strong, until there are larger RCTs of better
      methodological quality, it is not recommended that practitioners treat
      hypertriglyceridemia with omega-3 fatty acid supplementation in lieu of lipid
      lowering medications.

PMID- 15495693
TI  - Caught in the middle: experiences of tobacco-dependent nurse practitioners.
AB  - PURPOSE: To explore how tobacco-dependent nurse practitioners (NPs) describe
      their experiences with health promotion and disease prevention practices with
      patients who smoke. DATA SOURCES: Twelve NPs who completed a graduate level NP
      program of study participated in face-to-face interviews and/or online chat room
      interviews. CONCLUSIONS: Participants' responses revealed three themes relevant
      to their experience as tobacco-dependent clinicians with health promotion
      responsibilities. These themes centered around (a) living as an insider in the
      world of tobacco addiction, (b) having the outside-in view of living with a
      tobacco addiction, and (c) being caught in the middle of a tobacco addiction.
      IMPLICATIONS FOR PRACTICE: All of the tobacco-dependent participants described
      limited smoking-cessation interventions with their patients. A barrier to
      implementation of more aggressive interventions, perhaps, is the provider's own
      tobacco addiction. With increasing evidence that tobacco-dependent health care
      professionals are not adequately intervening with tobacco-dependent patients,
      effective strategies are needed to assist and/or support not only tobacco
      dependent patients but providers as well.

PMID- 15495694
TI  - Flu vaccines and patient decision making: what we need to know.
AB  - PURPOSE: To describe and compare patient-perceived barriers and motivators and
      decision-making conflict between two groups of hospitalized patients, those who
      received flu vaccines and those who did not. DATA SOURCES: Data collection
      included extracting data from databases and mailing two surveys to 436 discharged
      patients. One hundred eight patients participated in the study. CONCLUSIONS: Top
      motivators for obtaining a flu vaccine included previous vaccination (93%) and
      provider recommendation (62%). Top barriers included fear of side effects from
      the vaccine (35%) and fear of contracting the flu (30%). Motivators, barriers,
      and patient decisional conflict differed depending upon the patient's vaccination
      status. IMPLICATIONS FOR PRACTICE: Given the potential negative consequences of
      contracting the flu, prevention is the best strategy. Prevention is contingent
      upon motivating patients to obtain an annual flu vaccine. Recommending flu
      vaccinations, offering vaccinations in convenient locations free of charge, and
      discussing perceived barriers with patients may increase vaccinations among high
      risk patients. Helping to clarify the advantages and disadvantages from the
      patient's perspective may decrease decisional conflict and increase vaccination
      rates.

PMID- 15495695
TI  - The process of changing health risk behaviors: an Oregon rural clinic experience.
AB  - PURPOSE: A counseling intervention was conducted by nurse practitioners (NPs) at
      a rural clinic in Oregon. The intervention was designed to help individuals
      change health risk behaviors. Three focus groups were conducted to aid in
      understanding the barriers to changing health behaviors and to identify resources
      that rural individuals needed to succeed in behavior change. DATA SOURCES:
      Quantitative data were collected using appraisal forms that were specific to five
      behaviors. Qualitative data were from written comments submitted by focus group
      participants in answer to questions sent prior to each meeting and from written
      summaries of focus group meetings submitted by the focus group leader.
      CONCLUSIONS: Most participants were not successful in changing their health
      behaviors. The issues raised in the focus group discussions provide an overview
      of the barriers to health behavior change as perceived by a group of adults in a
      rural environment. Both individual lack of will and the rural community
      environment were barriers to adopting new health behaviors. IMPLICATIONS FOR
      PRACTICE: NPs in rural health care clinics could provide important support for
      individuals attempting to adopt new health behaviors. Specific suggestions from
      focus group participants included discussing risky behaviors more often, forming
      support groups that do not charge a fee, and developing a peer-mentoring program.

PMID- 15495696
TI  - Choosing healthy behaviors: one small step for womankind.

PMID- 15495697
TI  - RE: Simpson, K. R., & Atterbury, J. (2003). Trends and issues in labor induction
      in the United States: implications for practice.

PMID- 15495698
TI  - The evolution of bed rest as a clinical intervention.
AB  - Bed rest as a therapy can be traced back to Hippocrates and has been used for
      many types of illnesses since then. It is still commonly used as an intervention
      in pregnancy despite known physiological and psychological side effects. Some
      historical and social reasons why nurses and other health care providers are slow
      to change practice are provided. Evidence from randomized trials is urgently
      needed to support or refute the use of bed rest in pregnancy.

PMID- 15495699
TI  - Is there logic behind fetal monitoring?
AB  - Practitioners of biomedicine pride themselves on making logical decisions based
      on scientific fact and research evidence. However, continuous electronic fetal
      monitoring, as it is applied in contemporary North American obstetric practice,
      does not stand up to the rules of logic or the application of empirical evidence.
      In the face of growing evidence against the efficacy of continuous electronic
      fetal monitoring for improving birth outcomes, perinatal health care providers
      need to critically evaluate the arguments that supported its inception and
      consider whether its continued application can be defended.

PMID- 15495700
TI  - Keeping birth normal: research findings on midwifery care during childbirth.
AB  - OBJECTIVE: This study describes processes and outcomes of midwifery care through
      narratives told by exemplary midwives. DESIGN: Narrative analysis. SETTING:
      Midwifery practices in hospital, birth center, and home settings. PARTICIPANTS:
      Purposive sample of 14 midwives drawn from a large national Delphi panel on
      exemplary midwifery practice. DATA ANALYSIS: Systematic analysis of interview
      data was conducted until interpretive consensus was achieved across all text and
      codes. Results were compared with two prior qualitative studies conducted by the
      first author on midwifery practice for congruence and emergence of new findings.
      RESULTS: The support of normalcy was identified as a significant process of
      midwifery care during labor and birth. CONCLUSIONS: The midwives believed that
      birth is normal, and many of their actions were specifically aimed toward the
      support of it as a physiologic, rather than pathologic, process. Through their
      words, we see subtle care processes focused on meeting a woman's individual needs
      and tapping into her personal strength. Implications for practice and further
      research to link their approach to caring for women with perinatal outcomes are
      reviewed.

PMID- 15495701
TI  - Influences of income, education, age, and ethnicity on physical abuse before and
      during pregnancy.
AB  - OBJECTIVE: To examine the influence of socioeconomic status, education,
      ethnicity, and age on the prevalence of intimate partner abuse before and during
      pregnancy. DESIGN: Retrospective correlational analysis. SETTING: Data were
      collected at six postpartum maternity settings. PARTICIPANTS: 1,004 women from
      six ethnic groups. MAIN OUTCOME MEASURE: Prevalence of intimate partner violence.
      RESULTS: 15.9% of study participants reported physical abuse by their current
      partner and 5.2% reported abuse during pregnancy. Decreased income, not having a
      high school education, and ethnicity were significantly related to current abuse
      and abuse during pregnancy in bivariate analyses. Having less than a high school
      education emerged as the most significant predictor of both abuse variables in
      multivariate analyses. African American and Puerto Rican women had the highest
      incidence of abuse in their current relationship. No significant differences were
      found in rates of abuse during pregnancy among women from different ethnic
      groups. CONCLUSIONS: The results of this analysis support the notion that abuse
      is most prevalent among the most disadvantaged women. However, it is not income
      per se, but rather the highly related variables of education and ethnicity that
      have the largest effect. Abuse occurs frequently among all women, warranting
      universal screening during health care encounters. Further research is needed to
      evaluate relationships between education, ethnicity, income, and abuse.

PMID- 15495702
TI  - Effect of an intimate partner violence educational program on the attitudes of
      nurses.
AB  - OBJECTIVE: To examine the effect of an intimate partner violence (IPV)
      educational program on the attitudes of nurses toward victims. DESIGN: A quasi
      experimental study utilizing a pretest and posttest. SETTING: An urban health
      care system. PARTICIPANTS: Fifty-two inpatient nurses completed both the pretest
      and posttest. INTERVENTION: One-hour and 3-hour IPV educational programs. MAIN
      OUTCOME MEASURES: Change in attitude was determined by scores from the Public
      Health Nurses' Response to Women Who Are Abused (PHNR), a standardized
      questionnaire that measures nurses' reactions to an IPV scenario. Parallel forms,
      each with a different scenario, were administered before and 2 months after the 1
      hour and 3-hour educational sessions. Scores were analyzed using a repeated
      measures analysis of variance followed by multiple comparisons with Bonferroni
      adjustments. RESULTS: Nurses' PHNR scores increased significantly after attending
      the 1-hour session if they had previous IVP education and after the 3-hour
      session if they had no previous IVP education. CONCLUSION: Educational offerings
      should be tailored for nurses. For nurses with previous IVP education, offer a 1
      hour update. For nurses with no previous IVP education, provide a 3-hour
      educational session. Further study is needed to determine if change in nurses'
      attitudes translates into improved screening, identification, and intervention
      for IPV victims.

PMID- 15495703
TI  - Interaction between feeding method and co-sleeping on maternal-newborn sleep.
AB  - BACKGROUND: Previous studies have demonstrated that breastfed newborns spend more
      time awake than bottle-fed newborns, breastfeeding mothers have more fragmented
      sleep than bottle-feeding mothers, and mother-newborn sleeping arrangements may
      affect the sleep/wake pattern of mother-newborn pairs. OBJECTIVE: To address the
      unsolved question of whether there is an interaction between type of feeding and
      sleeping arrangements that affects postpartum sleep during the 4th postpartum
      week. DESIGN: Correlational, two-way design using feeding method and location of
      newborn at night as independent variables, and sleep patterns as the dependent
      variables. SETTING: Patient's home during 4th week after giving birth.
      PATIENTS/PARTICIPANTS: First-time mothers and their newborns (n = 33). MAIN
      OUTCOME MEASURES: Amount of total sleep, amount of night sleep, number of night
      awakenings, and number of sleep periods in 24 hours using a modified version of
      the self-report sleep instrument by Barnard and Eyres. RESULTS: Breastfed
      newborns had less total sleep per day than bottle-fed newborns, and breastfeeding
      mothers had more sleep periods in 24 hours than bottle-feeding mothers.
      Breastfeeding mothers slept more than bottle-feeding mothers when co-sleeping,
      but bottle-feeding mothers' sleep was unaffected by location of newborn. Average
      total sleep for 4-week-old newborns was about 14 hours daily. CONCLUSIONS: More
      sleep was obtained when breastfeeding mothers slept with the newborn. Methods or
      devices that allow breastfeeding mothers and newborns to sleep next to each other
      in complete safety need to be developed.

PMID- 15495704
TI  - Evaluation of Korean newborns with the Brazelton Neonatal Behavioral Assessment
      Scale.
AB  - OBJECTIVES: To determine the unique responses of a group of Korean full-term
      newborns and to describe the pattern of behavior observed in the first few days
      of life. DESIGN: A descriptive study describing the behavioral patterns of Korean
      newborns using the Neonatal Behavioral Assessment Scale. PARTICIPANTS: Fifty
      newborns aged 1 to 3 days in a nursery of a large tertiary hospital in Daegu,
      Korea. RESULTS: Overall scores were at moderate levels in six clusters. These
      were (a) Response Decrement, (b) Social Interactive, (c) Motor System, (d) State
      Organization, (e) State Regulation, and (f) Autonomic System. Newborns showed
      good overall tone and activity level and low amount of irritable behavior.
      Although reflex responses were generally normal, Korean newborns showed
      particularly weak responses in standing and walking reflexes. Maternal variables
      such as employment and previous pregnancy history were related to the scores on
      the Neonatal Behavioral Assessment Scale. CONCLUSION: The results of the study
      indicate that Korean newborns showed a moderate level of autonomic stability and
      motor control and overall good state organization. These findings also provide
      some evidence that the mother's health status and lifestyle during the pregnancy
      may affect newborn behavior after birth.

PMID- 15495705
TI  - Support from health care providers and the psychological adjustment of
      individuals experiencing infertility.
AB  - OBJECTIVE: To examine the relationship between support from health care providers
      and psychological adjustment for men and women experiencing infertility. DESIGN:
      Survey research using confidential self-administered questionnaires.
      PARTICIPANTS: One hundred twenty individuals experiencing infertility within
      their couple relationship participated in this study (60.8% women; 29.3% men).
      MAIN OUTCOME MEASURES: Perceived support from health care providers was
      hypothesized to be related to stress, anxiety, and depression. Various treatment
      variables were held constant in the regression analyses. RESULTS: For women,
      perceived support from health care providers did not predict levels of stress,
      depression, or anxiety. For men, greater levels of perceived support from health
      care providers predicted lower levels of stress (FChange = 4.90, p < .05) and
      anxiety (FChange = 4.81, p < .05) but not depression. CONCLUSION: Much research
      exists indicating that friend and family support is a buffer to negative
      psychological adjustment for women. The results of this study emphasize that the
      study of support from nurses and other health care providers might provide
      greater understanding of ways to buffer negative psychological adjustment for men
      experiencing infertility in the couple relationship.

PMID- 15495706
TI  - Women with primary antibody deficiencies requiring IgG replacement therapy: their
      perception of prenatal care during pregnancy.
AB  - OBJECTIVE: To investigate how a group of women with primary antibody deficiencies
      (PAD) and receiving replacement therapy with IgG experienced the care they
      received in their prenatal clinics in relation to PAD and IgG therapy. DESIGN: An
      exploratory study using a written questionnaire. SETTING: The study originates
      from an immunodeficiency unit but evaluates care experienced at prenatal clinics.
      PARTICIPANTS: Nine women (25-43 years) attending an immunodeficiency unit and who
      fulfilled inclusion criteria for simultaneously having PAD, replacement IgG
      therapy, and full-term pregnancy (the latter within the past 5 years). MAIN
      OUTCOME: Women's perception of the response of midwives and physicians at their
      prenatal clinics to their PAD and IgG therapy during pregnancy. RESULTS: Women
      perceived that the obstetricians and the midwives had insufficient knowledge
      about PAD and IgG replacement therapy. Two women reported that their IgG therapy
      during pregnancy had been questioned. All nine women felt marginalized and
      unheard by staff regarding their PAD and need for IgG therapy. However, the women
      were satisfied with the checkups regarding the pregnancy as such. CONCLUSIONS:
      This study is the first attempt to investigate the prenatal experience of women
      with PAD (Search of PubMed, 1980 to present, including search terms primary
      immunodeficiency, pregnancy, and prenatal care). This study demonstrates that
      increased knowledge about PAD and IgG replacement therapy among midwives and
      physicians working in prenatal care clinics is needed. This can prevent
      misleading advice that puts the health of the mother and her fetus at risk.
      Sensitizing staff about this special group of women can create conditions in
      which women feel respected, heard, and satisfied with their prenatal care.

PMID- 15495707
TI  - Recipients of oocyte donation: an integrative review.
AB  - OBJECTIVE: To conduct a systematic review of published research to provide a
      synthesis of the psychosocial characteristics of donor oocyte recipient women.
      DATA SOURCES: The sample of published studies was selected from 1983 to September
      2002. Retrieval of the studies used online computer searches from CINAHL,
      MEDLINE, PsycINFO, and Wilson's Social Science Abstracts using the terms
      reproduction techniques, in vitro fertilization, oocyte donation, oocyte
      recipients, and egg donation; citations from references and bibliographies of
      previously located articles; and two 60-minute retrieval sessions with a
      librarian specializing in health science literature. STUDY SELECTION: The
      majority of studies retrieved were completed in the natural sciences. The final
      sample resulted in 16 studies. DATA EXTRACTION: Each study was read and the data
      were extracted using a survey instrument developed by the investigator. DATA
      SYNTHESIS: Multiple methodologies were used in the sample; most were exploratory,
      retrospective, and descriptive studies. Thus, the data were analyzed using a
      qualitative discursive approach. A total of 827 donor oocyte recipient women
      participated in the studies. CONCLUSIONS: Published research investigating the
      psychosocial characteristics of donor recipient women was categorized into six
      focused areas: motivation; desired donor characteristics; selection of a known
      versus an anonymous donor; demographic, educational, and psychosocial profiles;
      disclosure of the method of conception to family members, friends, and the
      resulting child; and the relationship between the oocyte recipient and her
      resulting offspring. Research involving the psychosocial aspects of donor oocyte
      recipient women is in the infancy stage.

PMID- 15495708
TI  - Youth is a gift of nature, but aging is a work of art: health issues of older
      women.

PMID- 15495709
TI  - Global aging: implications for women and women's health.
AB  - The world's older population has been growing for centuries; however, the pace of
      this growth is accelerating rapidly. According to the U.S. Census Bureau, by
      2030, more than 60 countries will have 2 million or more older people. Population
      aging represents a "success story," with increasing numbers of people worldwide
      enjoying additional years of life. However, the sustained increase in numbers of
      older people (usually defined as persons over the age of 65) poses many
      challenges to policy makers and health care providers around the world. As the
      world population ages, we are just beginning to understand the social, economic,
      and political implications of the "age wave." The majority of older people are
      women, thus the implications of population changes for women and women's health
      are astounding. Nurses can take a national and world leadership role to
      adequately address the health care needs of increasing numbers of older women.

PMID- 15495710
TI  - Health promotion for mid- and later-life women.
AB  - Health outcomes in later life are dependent in part on activities started in
      midlife. Primary and secondary prevention strategies include seeking healthier
      life choices, early detection of disease, and specific disease avoidance through
      immunization and other activities. The recommendations for various screenings and
      health care for postmenopausal women have changed rapidly over the past 2 years
      but still include the basics of nutrition, exercise, testing for common
      illnesses, and control of existing health problems.

PMID- 15495711
TI  - Postmenopausal hormone replacement and cardiovascular disease: incorporating
      research into practice.
AB  - The long-standing practice of prescribing hormones to postmenopausal women was
      based in part on the observation that following menopause, women's incidence of
      cardiovascular diseases such as atherosclerosis, myocardial infarction, and
      cerebral vascular accident increased. Recent large-scale research has shown an
      increase in cardiovascular events for postmenopausal women receiving estrogen
      replacement in oral form. This article examines research on positive effects of
      hormone replacement therapy, discusses what is known about the development of
      cardiovascular disease in women, and evaluates recent research that has shown
      increased cardiovascular risk in women receiving hormone replacement. It
      concludes with recommendations for preventing cardiovascular disease in women.
      This is essential information for nurses, who need to be informed of ways to
      maintain their own health while serving as sources of health information for the
      public at large.

PMID- 15495712
TI  - Elder mistreatment in women.
AB  - Elder mistreatment is a serious syndrome that affects more than 1.5 million older
      Americans every year. Actions such as abuse, neglect, exploitation, and
      abandonment by caregivers, relatives, friends, or acquaintances can have
      devastating sequelae for the elderly. Such actions may be intentional or
      unintentional, but the detrimental outcomes for older individuals can destroy the
      elder's quality of life and health. A lack of empirical research addresses gender
      differences in elder mistreatment. There is also confusion and debate over what
      constitutes elder mistreatment in older women versus what is domestic violence
      that has continued into later life. Professional nurses need to include both
      types of screening for their older female patients in order to address both types
      of family violence.

PMID- 15495713
TI  - Empowering older women: strategies to enhance their health and health care.
AB  - Older persons, especially older women, report that often their needs are not met
      in health care encounters. Lack of active participation by the patient is a major
      reason for this dissatisfaction. This article reviews research on older women's
      socialization that discourages them from challenging the status quo in
      interactions with others. It suggests ways that health care providers can empower
      female patients: They can encourage active participation during health care
      encounters, and they can help patients prepare for encounters so they can have
      their needs met.

PMID- 15495714
TI  - I would like to share our readiness for the next earthquake after the heaviest
      one in Turkey in 1999.

PMID- 15495715
TI  - Neumann and Peeples [Milit Med 2001; 166:v] found no clear association between a
      theistic religion index and treatment adherence or success in an outpatient
      nicotine reduction treatment program.

PMID- 15495716
TI  - Cardiopulmonary and mental health diagnoses surrounding the September 11
      terrorist acts in a military population.
AB  - BACKGROUND: In addition to psychological disorders, emotional stress can trigger
      a chain of neurohumoral imbalances that can manifest as cardiopulmonary
      complaints. No studies were identified that used objective clinical data on
      complaints after the terrorist attacks of September 11, 2001. The purpose of this
      descriptive study was to identify all cardiopulmonary and psychological diagnoses
      among active duty personnel seeking care at a military treatment facility and/or
      its ancillary facilities before and after September 11, 2001. METHODS: The study
      population included 40,981 active duty military personnel between August 13, 2001
      and October 9, 2001 (4 weeks before and 4 weeks after September 11, 2001).
      Demographic and diagnostic data were obtained from the Composite Health Care
      System for each visit during the study period. The outcomes of interest were
      psychological and cardiopulmonary diagnoses. RESULTS: There were 19,595 clinic
      visits before September 11, 2001 compared to 19,207 clinic visits in the 4 weeks
      after September 11. There was no increase in total psychological diagnoses in the
      postexposure period, compared with the preexposure period (risk ratio (RR), 0.97;
      95% confidence interval (CI), 0.84-1.11). The only statistically significant
      finding was a decrease in diagnoses of psychoses (RR, 0.62; 95% confidence
      interval, 0.42-0.91). However, diagnoses of depressive disorders were increased
      in the postexposure period (RR, 1.61; 95% CI, 0.89-2.90; p = 0.11). Total
      cardiopulmonary diagnoses did not increase in the postexposure period, compared
      with the preexposure period (RR, 0.96; 95% CI, 0.91-1.02). CONCLUSIONS: This
      descriptive study failed to identify evidence that any changes in cardiopulmonary
      or mental health diagnoses were attributable to September 11 terrorist attacks.
      In the unfortunate event of another national tragedy, it is recommended that
      health care professionals administer a questionnaire to determine why patients
      are seeking care after the tragedy. These data could be linked to International
      Classification of Diseases data to determine the effects of the tragedy on the
      health of personnel and their utilization of health care services.

PMID- 15495717
TI  - Diagnosis and treatment of a ruptured ectopic pregnancy in a combat support
      hospital during Operation Iraqi Freedom: case report and critique of a field
      ready sonographic device.
AB  - This case report describes a novel diagnostic approach for ectopic pregnancy in a
      combat environment. We diagnosed a ruptured ectopic pregnancy at our combat
      support hospital by using the SonoSite 180 Plus ultrasound device (SonoSite,
      Bothell, WA). The live ectopic pregnancy was immediately identified and the
      entire pelvic anatomy was easily assessed within 5 minutes. The SonoSite
      ultrasound device proved to be easy to use, durable, and reliable. It produced
      high-quality images in a variety of applications. The handheld SonoSite 180
      ultrasound device is sufficiently portable to be used effectively in a combat
      support hospital or field situation, such as a forward surgical team. This combat
      experience suggests that a handheld ultrasound device may also have great utility
      during patient transport for civilian hospitals.

PMID- 15495718
TI  - Suspected meningococcal meningitis on an aircraft carrier.
AB  - A suspected case of meningococcal meningitis was diagnosed in a 24-year-old
      sailor onboard an aircraft carrier at sea in 2003. He was immediately confined to
      the ship's hospital ward under respiratory isolation precautions and was treated
      with intravenously administered antibiotics. His illness resolved without
      sequelae. A total of 99 close contacts from the ship were identified and given
      antibiotic prophylaxis, with directly observed therapy. British public health
      authorities were contacted to trace and treat persons identified as close
      contacts during a port call a few days before presentation. Managing a
      communicable disease such as meningococcal meningitis in the austere shipboard
      environment represents a unique challenge to military medical personnel.
      Successful management is possible through prompt treatment, respiratory
      isolation, and open communication between primary health care providers and
      public health officials. The identification of shipboard close contacts and other
      infection control procedures used by the ship's medical department are reviewed.

PMID- 15495719
TI  - Prevalence of leptospira antibodies in U.S. Army blood bank donors in Hawaii.
AB  - Leptospirosis is a zoonotic infection of worldwide distribution that is commonly
      endemic in tropical regions. In the United States, the annual incidence rate in
      the state of Hawaii is approximately 30 times higher than that reported
      nationally. U.S. troops deployed to disease-endemic tropical environments and
      those training in the state of Hawaii are potentially at high risk for acquiring
      leptospirosis. Serum and risk factor data were obtained from 488 blood donors
      attending military-sponsored blood drives on the island of Oahu. Testing of sera
      for the presence of Leptospira-specific antibodies was performed with microscopic
      agglutination testing (MAT). Seven active duty U.S. Army soldiers were found to
      be seropositive by MAT (seroprevalence, 1.4%), 2 of 76 newly arrived residents
      (2.6%) and 5 of 412 established residents (1.2%). Positive MAT results were
      statistically more common among female subjects and those 18 to 30 years old.
      Seropositivity was not associated with specific exposures or prolonged residence
      in the state of Hawaii.

PMID- 15495720
TI  - Ventricular injury following cranial gunshot wounds: clinical study.
AB  - Gunshot wounds to the head are usually fatal injuries, despite all medical and
      surgical interventions. Ventricular injury is a poor prognostic factor-for
      penetrating cranial gunshot wounds. Intraventricular hemorrhage and ventricular
      lacerations are the main components of such injuries. The incidence, management,
      and outcomes of cases of ventricular injury secondary to cranial gunshot wounds
      that were treated during a 9-year period at Gulhane Military Medical Academy were
      examined. The study group consisted of 67 consecutive patients who were admitted
      to the Department of Neurosurgery with the diagnosis of ventricular injury, with
      different penetration sites. The patients had been injured by either bullets or
      shrapnel. Surgical treatment was performed for all patients with ventricular
      injuries and 22 (32.8%) died. Ventricular injury in cranial gunshot wounds is a
      complex severe type of trauma that requires serious treatment. Early radiological
      diagnosis and accurate treatment frequently had lifesaving roles for these
      patients.

PMID- 15495721
TI  - Class 3 dental treatment time.
AB  - OBJECTIVE: Dental emergencies take soldiers away from their assigned duties. The
      objective of this project was to determine the average clinical treatment time
      needed to correct nondeployable dental conditions using actual treatment times
      noted in an electronic scheduler. METHODS: The Fort Hood Class Three Intercept
      Clinic forwarded their daily treatment logs to the Dental Command for each week
      from November 1, 2002 through February 13, 2003. Clinical treatment times and
      types of services provided for dental fitness category (DFC) 3 conditions were
      tracked with the Corporate Dental Application scheduler. RESULTS: The project
      identified 398 DFC 3 soldiers who were scheduled to receive treatment at the Fort
      Hood Class Three Intercept Clinic between November 1, 2002 and February 13, 2003.
      Twenty-three of those soldiers did not receive treatment; therefore, the total
      sample size was 375. On average, it required 2.2 hours of clinical dental
      treatment time to make a DFC 3 soldier dentally deployable. CONCLUSIONS: The
      findings of this study suggest that treating DFC 3 conditions is time-intensive
      but most DFC 3 soldiers can be treated in approximately 2 hours in an efficient
      and properly staffed dental clinic. Without proper preventive education and
      maintenance, these soldiers may develop additional oral disease and may require
      repeated episodes of increasingly intensive dental treatment.

PMID- 15495722
TI  - Visceral leishmaniasis in a soldier returning from Operation Enduring Freedom.
AB  - This report presents a case of visceral leishmaniasis in a soldier returning from
      Operation Enduring Freedom. During the United States' last major military
      conflict, Operation Desert Storm, the diagnosis of multiple cases of visceral
      leishmaniasis led to policy changes, including a temporary ban on troop blood
      donation. This case demonstrates the applicability of recently developed
      Leishmania polymerase chain reaction and serological assays when conventional
      methods of diagnosis, such as tissue microscopy and culture, fail.

PMID- 15495723
TI  - Cold injuries among Israeli soldiers operating and training in a semiarid zone: a
      10-year review.
AB  - Cold weather injuries (CIs) in 242 incidences among Israeli soldiers, who were
      operating and training in a relatively warm country, were reviewed. Peripheral
      CIs accounted for 55% of all CIs, whereas hypothermia accounted for 45%. A
      significant relationship was found between peripheral CIs and continuous
      operations, characterized by prolonged static exposures to a relatively high
      environmental cold stress. A significant relationship was also found between
      hypothermia cases and training activities, characterized by relatively short
      exposures to a low environmental cold stress in the absence of adequate
      protective clothing for the cold. Static exposure to a cold environment while
      wearing wet clothing was found to be the leading cause of both CI types.
      Peripheral CI prevention requires the improvement of protective clothing for the
      cold, with special emphasis on protective gear for the extremities. Hypothermia
      prevention requires increased awareness of military regulations regarding cold
      weather behavior, especially the importance of changing wet clothing during
      static periods of the training program.

PMID- 15495724
TI  - Neoplasms in the Navy, 1998-2000: a descriptive analysis of the Physical
      Evaluation Board database.
AB  - Records with diagnoses for neoplasms (International Classification of Diseases,
      Ninth Revision, Clinical Modification, codes 140-239) contained in the U.S. Navy
      Physical Evaluation Board database for 1998 to 2000 were identified (n = 427
      cases, 342 malignant and 85 benign). The four most common sites of occurrence
      were other and unspecified sites (27%), lymphatic and hematopoietic tissues
      (22%), benign neoplasms (20%), and genitourinary organs (12%). Crude overall
      cancer rates were 37.7 cases per 100,000 male subjects and 55.4 cases per 100,000
      female subjects. Overall, Hodgkin's disease was the most common diagnosis, with a
      rate of 3.3 cases per 100,000 population. It also had the highest rate among male
      subjects, with 3.5 cases per 100,000 male subjects of all ages and 4.2 cases per
      100,000 men more than 40 years of age. For women, breast cancer had the highest
      rate of 8.5 cases per 100,000 subjects. These values are consistent with or lower
      than the published reports of U.S. Navy and national rates. Ongoing surveillance
      of malignancies among Navy personnel is an important part of force health
      protection.

PMID- 15495725
TI  - Severe anemia following uvulectomy in Kenya.
AB  - Uvulectomy is a common practice in eastern Africa for treatment of a variety of
      throat conditions. Traditional healers perform the procedure. I present a case
      report to illustrate a complication of uvulectomy. This is a report of a child
      who presented with severe anemia secondary to uvulectomy performed for treatment
      of chronic cough. This case report is intended to illustrate a procedure not
      commonly performed by western otolaryngologists and to describe the management of
      a severe complication. Western physicians are increasingly being tasked in
      medical situations in which they encounter traditional medical practices outside
      of their scope of training. The intent of this report is to familiarize western
      physicians with one such procedure and its potential complications.

PMID- 15495726
TI  - An isolated long thoracic nerve injury in a Navy Airman.
AB  - A palsy of the long thoracic nerve of Bell is a cause of scapular winging that
      has been reported after trauma, surgery, infection, electrocution, chiropractic
      manipulation, exposure to toxins, and various sports-related injuries that
      include tennis, hockey, bowling, soccer, gymnastics, and weight lifting. Scapular
      winging can result from repetitive or sudden external biomechanical forces that
      may either exert compression or place extraordinary traction in the distribution
      of the long thoracic nerve. We describe an active duty Navy Airman who developed
      scapular winging secondary to traction to the long thoracic nerve injury while
      working on the flight line. A thorough history and physical is essential in
      determining the mechanism of injury. Treatment should initially include
      refraining from strenuous use of the involved extremity, avoidance of the
      precipitating activity, and physical therapy to focus on maintaining range of
      motion and strengthening associated muscles, with most cases resolving within 9
      months.

PMID- 15495727
TI  - Hemostatic dressings for the first responder: a review.
AB  - The military is interested in finding a hemostatic dressing that is effective in
      controlling hemorrhage from combat wounds, relatively inexpensive, and easy to
      transport. The fibrin dressing has existed for decades, but the military has been
      reluctant to use the dressing because it is not Food and Drug Administration
      approved, fairly expensive, and difficult to apply on certain wounds. Newer
      dressings such as the microporous polysaccharide hemosphere (TraumaDEX), mineral
      zeolite (QuikClot), poly-N-acetylglucosamine (HemCon), and microporous hydrogel
      forming polyacrylamide (BioHemostat) dressings have addressed these deficiencies
      in that they are relatively inexpensive, easy to transport, and easy to apply.
      However, the effectiveness of these new dressings on wounds sustained in combat
      is still questionable according to studies and anecdotal reports from Operation
      Iraqi Freedom. More research is needed to draw definite conclusions about the
      effectiveness of these dressings in a combat setting.

PMID- 15495728
TI  - Small bowel injuries in penetrating abdominal trauma during war: ten-year follow
      up findings.
AB  - BACKGROUND: Injuries of the small intestine are common in penetrating abdominal
      trauma. This article presents 10-year follow-up results for 23 patients with
      penetrating small bowel injuries who were treated in Nova Gradiska City Hospital
      during the 1991-1992 war in Croatia. The early hospital mortality rate was 13%
      (three deaths), and good results were found for 16 (84%) of 19 patients after 10
      years. METHODS: The hospital charts of 23 patients who sustained small bowel
      injuries during an 8-month period were reviewed. Of 20 patients who survived, 19
      came for an examination and interview 10 years after injury. The following
      criteria were used: existence of an abdominal wall defect or hernia, bowel
      passage problems, and reoperations attributable to the small bowel injury.
      RESULTS: Early results revealed adhesive peritonitis and ileus for three patients
      demanding early reoperation (13%) and a hospital mortality rate of 13% (three
      deaths, mainly attributable to multiple injuries). Ten years after injury, 16
      patients had no problems, whereas 3 reported occasional abdominal pain.
      CONCLUSION: Penetrating abdominal injuries in war demand urgent diagnostic
      procedures and, in almost all cases, urgent laparotomy. In cases with no evidence
      of abdominal penetration and cases involving multiple injuries, an aggressive
      approach reduces the risk of missing small bowel injuries. Use of established
      principles for surgical management of small bowel injuries yields good results
      and low incidences of late complications and difficulties.

PMID- 15495729
TI  - An analysis of maxillofacial fractures: a 5-year survey of 157 patients.
AB  - The purpose of this study was to review retrospectively the outcomes for 157
      patients treated for maxillofacial fractures between 1994 and 1999 at one
      military hospital in Turkey. Significant data were collected according to age,
      gender, time of injury, type of facial injuries, cause of injury, treatment
      methods, and postinjury and postoperative complications. Fractures resulting from
      gunshot wounds were excluded in this study. Fractures were examined in two groups
      according to the type of fracture, i.e., isolated or combined. Methods of
      fixation with closed or open reduction were used to treat the fractures. Fixation
      was performed with miniplates, compression plates, microplates, reconstruction
      plates, and wires for open reduction, and stabilization was performed with arch
      bars for closed reduction. Complications were recorded in two groups, i.e.,
      postinjury and postoperative complications. There were 151 male patients (96.18%)
      and 6 female patients (3.82%). The patients ranged in age from 15 to 62 years
      (mean, 22.8 years). In our study, it was determined that the most significant
      causes of maxillofacial fractures were traffic accidents (69 cases, 43.95%) and
      fighting (42 cases, 26.75%). Most fractures were in the mandible (161 fractures).
      It was observed that most of the mandibular fractures were in the body (49
      fractures, 30.43%) and condylar (42 fractures, 26.09%) regions. Of the 223
      maxillofacial fractures, 63.68% (142 fractures) were treated with closed
      reduction and 36.32% (81 fractures) were treated with open reduction. Postinjury
      complications included infections (local infection or osteomyelitis), nerve
      injuries (alveolaris inferior, facial, lingual, and infraorbital nerves), and a
      salivary gland fistula, and postoperative complications included infection,
      facial asymmetry, and malocclusion.

PMID- 15495730
TI  - Treatment of infected tibial nonunions with debridement, antibiotic beads, and
      the Ilizarov method.
AB  - This study of 10 patients presents the early results of a protocol of
      debridement, antibiotic bead placement, and use of the Ilizarov method with a
      circular external fixator for treatment of infected nonunions of the tibia in a
      military population. The nonunions resulted from high-energy fractures in nine
      cases and an osteotomy in one. The Ilizarov techniques used were transport (five
      cases), shortening and secondary lengthening (two cases), minimal resection with
      compression (one case), and resection with bone grafting (two cases). Flap
      coverage was required for five patients. There were two recurrences of infection
      (20%) among patients with the most compromised soft tissue. Only 50% of patients
      were able to perform limited duties while wearing the external fixator. Only four
      patients returned to active duty; however, three patients from special operations
      units were able to return to jump status. Six patients underwent medical
      retirement because of insufficient function, resulting from decreased ankle or
      knee range of motion and arthrosis or muscle weakness.

PMID- 15495731
TI  - Does membership in veterans' service organizations influence use of the
      Department of Veterans Affairs as the usual source of care?
AB  - Veterans' service organizations (VSOs) provide outreach regarding veterans'
      benefits. Medical care provided by the Department of Veterans Affairs (VA) is one
      such benefit that has improved health and quality of life. This study evaluates
      the characteristics of veterans who report VSO membership and who use the VA as
      their usual source of care, and it determines whether VSO membership influences
      the choice of a VA or non-VA facility as the usual source of care. The findings
      reveal that VSO members, compared with nonmembers, are Caucasian, older, retired,
      of lower income, and more functionally impaired. Veterans who use the VA,
      compared with non-VA users, are African American, of lower income, unemployed,
      and more functionally impaired. VSO members are more likely to use the VA as the
      usual source of care than are VSO non-members, with the effects varying according
      to race/ethnicity. Policy recommendations include increasing the diversity of VSO
      membership, because VSOs play an important outreach and informational role for
      veterans.

PMID- 15495732
TI  - User trial and insulation tests to determine whether shock-absorbing insoles are
      suitable for use by military recruits during training.
AB  - A user trial was undertaken to determine whether a shock-absorbing insole is
      suitable for military use. Two thicknesses of insole (3 mm and 6 mm) were studied
      and were issued to 38 Royal Marine recruits to wear in their military boots for
      weeks 12 to 30 of training. Biomechanical measurements showed that both
      thicknesses of insole significantly (p < 0.05) attenuated the peak pressures
      generated at heel strike and during forefoot loading when new (relative to a no
      insole condition) and that this was well maintained after wear. This was
      supported by mechanical tests conducted on the insoles. It was concluded that the
      insoles are sufficiently durable for military use. The main user complaint was
      that water retention reduced the comfort of the insoles; however, insulation
      tests conducted with a foot manikin indicated that switching from the current
      issue Saran insoles to the trial insoles would not increase the risk of recruits
      sustaining nonfreezing cold injuries to their feet.

PMID- 15495733
TI  - Viral gastroenteritis: the USS THEODORE ROOSEVELT experience.
AB  - Although the spread of disease on board Navy ships is not a novel concept, the
      medical department of the USS THEODORE ROOSEVELT recently experienced a
      significant outbreak of viral gastroenteritis while at sea. The impact on the
      crew and medical department is reviewed in this case report. The use of the Navy
      Disease Non-Battle Injury tracking system was validated. Furthermore, we proposed
      the placement of waterless, isopropyl alcohol-based, hand-cleaning systems in
      strategic locations throughout the ship, to help prevent and minimize the spread
      of future disease. Finally, more stringent recommendations regarding sick in
      quarters status and careful utilization of consumable resources are necessary
      components of an effective outbreak management strategy.

PMID- 15495734
TI  - Applied tension treatment of vasovagal syncope during pregnancy.
AB  - Vasovagal syncope is a common clinical problem that is often difficult and
      expensive to diagnose and treat. Applied tension is a behavioral treatment
      approach that has been demonstrated to be efficacious for the treatment of
      vasovagal syncope associated with injection phobia. The present case study
      evaluated the treatment of vasovagal syncope in a 41-year-old pregnant patient
      with injection phobia. The treatment included the use of applied muscle tension
      to increase blood pressure and prevent syncope during graduated exposure to
      increasingly greater anxiety-provoking stimuli. After completion of the
      treatment, the patient was able to undergo a blood draw and other medical
      procedures involving exposure to needles, with significantly reduced anxiety and
      no episodes of syncope. Applied tension is an effective and relatively
      inexpensive treatment for patients with vasovagal syncope related to injection
      phobia and may hold promise as a treatment for other types of syncope.

PMID- 15495735
TI  - Hemoptysis in a 28-year-old active duty soldier.
AB  - A 28-year-old African American male, originally from West Africa, presented with
      complaints of cough and hemoptysis. This case follows the patient through
      transfer to Walter Reed Army Medical Center and outpatient follow-up. Exploring
      this case illustrates how an Army physician may approach a soldier with
      hemoptysis. Additionally, this case demonstrates the management and treatment of
      his condition.

PMID- 15495736
TI  - Leadership development and health management education: concepts for focus and
      change.

PMID- 15495737
TI  - Managing today's complex healthcare business enterprise: reflections on
      distinctive requirements of healthcare management education.
AB  - In early 2001, the community of educational programs offering master's-level
      education in healthcare management began an odyssey to modernize its approach to
      the organization and delivery of healthcare management education. The community
      recognized that cumulative long-term changes within healthcare management
      practice required a careful examination of healthcare management context and
      manpower requirements. This article suggests an evidence-based rationale for
      defining the distinctive elements of healthcare management, thus suggesting a
      basis for review and transformation of master's-level healthcare management
      curricula. It also suggests ways to modernize these curricula in a manner that
      recognizes the distinctiveness of the healthcare business enterprise as well as
      the changing management roles and careers within these complex organizations and
      systems. Through such efforts, the healthcare management master's-level education
      community would be better prepared to meet current and future challenges, to
      increase its relevance to the management practice community, and to allocate
      scarce faculty and program resources more effectively.

PMID- 15495738
TI  - Competency identification and modeling in healthcare leadership.
AB  - In line with the current interest in leadership development across many
      industries today, a number of competency-based educational programming
      initiatives have been launched in professional education. As well, the National
      Summit on the Future of Education and Practice in Health Management and Policy in
      2001 called for the documentation of learning outcomes for continual educational
      improvement in health management and policy. The National Center for Healthcare
      Leadership (NCHL) subsequently launched a comprehensive, multi-stage process for
      identifying the competencies salient to distinguishing outstanding leadership
      performance in health management. This article describes the plan and the
      processes associated with NCHL's specification of a preliminary model of core
      competencies for leadership in health management, as well as the continued
      methods for refinement and validation of the model with both educators and
      practitioners in the field. The initial version of the NCHL Competency Model has
      facilitated field-wide dialogue regarding outcomes-based learning and assessment
      for both educational and professional development program planning. Subsequent
      development of the model will continue to stimulate open exchanges regarding
      pedagogical practice, as well as facilitate the design of leadership assessments
      for individuals, programs, organizations, and the field at large.

PMID- 15495739
TI  - Study of factors affecting the career advancement of women and
      racially/ethnically diverse individuals in healthcare management.

PMID- 15495740
TI  - A study of the decision factors for careers in health administration.

PMID- 15495741
TI  - Supreme Court clarifies the breadth of ERISA preemption.

PMID- 15495742
TI  - Linkages to leverage improvement in health.

PMID- 15495743
TI  - Implications of patient and physician decision making: an illustration in
      treatment options for coronary artery disease.
AB  - The objective of this study was to explore the extent to which patients and
      physicians desire patient participation in medical decision making. The cross
      sectional pilot study involved 92 patients with coronary artery disease (CAD) and
      50 physicians involved in treating patients with CAD. Desire to participate in
      making the decision between treatment options for CAD and factors that influence
      the decision were assessed. Physicians prefer to participate in shared decision
      making more often than do the patients (P = .016). When faced with clinical
      scenarios requiring a decision to be made between percutaneous transluminal
      coronary angioplasty and coronary artery bypass graft, patients and physicians
      tended to defer to one another to make the decision. Multinomial logistic
      regression models showed that the overriding factor influencing patient decision
      making was the physician's opinion (P < .0001) and the patient's preference was
      the overriding factor influencing physician decision making (P < .0001). Because
      patients tend to defer to physicians when making medical decisions, it is
      incumbent upon the physician to assure that the physician-patient dialogue
      reflects important information about the procedures (coronary artery bypass graft
      and percutaneous transluminal coronary angioplasty) and that preferences are
      acknowledged. This may impact greatly on achieving satisfactory health outcomes
      and patient satisfaction.

PMID- 15495744
TI  - Measuring risk perception among low-income minority primary care patients.
AB  - Studying patients' risk perceptions by ascertaining the probabilities of
      developing a disease is suboptimal, as patients might have difficulty using
      numerical expressions to depict the probabilities/chances of developing a
      disease. We surveyed patients at 2 community health centers and assessed risk
      perception by patients' self-reported chance of developing a disease (expressed
      in percentages), patients' relative chance of developing a disease compared to
      others' chance of developing a disease, and patients' ranked chances of
      developing different diseases. Many patients had difficulties understanding
      percentages and most patients overestimated their absolute risk. However, most
      patients indicated that they had a lower chance of developing diseases when
      compared to others. Patients with known risk factors (smoking) indicated a higher
      relative risk of developing an associated disease (lung cancer). Patients' ranked
      chances of developing different diseases were consistent with the actual
      frequency of developing a disease. Although patients had difficulty expressing
      risk in percentages, they estimated their risks well through comparisons with
      others and by ranking of disease frequencies.

PMID- 15495745
TI  - Healthy doctors, healthy communities.
AB  - Promoting health and eliminating disease are goals of Healthy People 2010, a
      national initiative for all communities. Physician-directed interventions that
      advance these principles are most effective when directed by clinicians who
      regularly participate in such healthy behaviors themselves. This pilot study
      describes an 8-week intervention, "Well-being for You and Your Patients," for
      first-year medical students to experience health behavior change. In the 2-hour
      sessions, students set goals for changing health behavior in 6 dimensions of
      wellness; report their progress; and enjoy a 30-minute change-of-pace wellness
      activity. The authors recommend adapting the course for medical student alumni to
      facilitate health behavior change with small groups of adults, school-age
      children, teens, and elders in churches, schools, community health centers, and
      other community-based organizations. Through continuing medical education and
      Grand Rounds, residents and physicians in practice could also be trained to
      implement specific behavioral change strategies.

PMID- 15495746
TI  - The value of collaboration in eliminating barriers to preventive care and
      screening among underserved populations.
AB  - Collaboration among a community's institutions and its residents can help
      increase the use of appropriate screening, preventive, and primary care services.
      To improve the health of the community, institutions must reach out to their
      colleagues and other stakeholders. They must not only deal with the structure of
      the healthcare delivery system but also be responsive to the characteristics of
      the local population groups they are trying to serve. Over the last several
      years, a group of 25 community-based partnerships across the country have used a
      multifaceted model to guide their work in making their communities healthier.
      Through a wide variety of initiatives tailored to local needs, they have not only
      improved people's health but also provided a series of benefits to the partnering
      organizations and the community as a whole.

PMID- 15495747
TI  - Empowering factors in repeat mammography: insights from the stories of
      underserved women.
AB  - Screening mammography can reduce breast cancer mortality. Although a significant
      percentage of underserved women obtain low income, minority mammograms regularly
      women underutilize mammography and rates of regular screening are also very low
      in the general population. By structuring focus groups around constructs from the
      Precede-Proceed Model, our study explored how these underserved women overcame
      barriers to be screened on a regular basis. Twenty-eight items were categorized
      as personal factors that helped them overcome the barriers: awareness and
      knowledge of risk factors (age and family history); knowledge and trust in early
      detection and treatment processes; personal responsibility about own health and
      well-being; and pride in self and satisfaction with one's own actions.

PMID- 15495748
TI  - Support systems: older adults with neurogenic communication disorders.
AB  - As the population of older adults increases, there is a corresponding increase in
      the number of individuals with communication disorders resulting from brain
      damage. The purpose of this article was to describe the effects of aphasia and
      dementia on language and communication, and to suggest support systems for
      improving communication and maximizing residual language abilities. For both
      these disorders, we address the psychosocial environment, the roles of
      professionals and caregivers, individual versus group therapy, and support
      groups. Finally, we report on 2 specific support groups, one for aphasia and one
      for Alzheimer's dementia, with which the authors have been involved for many
      years.

PMID- 15495749
TI  - Technology for community health alliances.
AB  - A community health alliance brings together divergent interests within a
      community for the betterment of personal and population health. In this report we
      describe how a community responsive strategy in Chicago is facilitating the
      improvement of healthcare by providing local information of what needs to be
      done, supporting change at the practice level to meet these needs, and initiating
      community-wide approaches to manage prevalent and important needs without waiting
      for direct involvement of health professionals.

PMID- 15495750
TI  - Preserving and maintaining optimal peri-implant soft-tissue complex for function
      and aesthetics.

PMID- 15495751
TI  - [Primary hyperparathyroidism. Main symptoms: fatigue, weakness, lack of appetite,
      constipation, mental disorders, bone pain].

PMID- 15495753
TI  - [Adjuvant and palliative anticancer treatment of colon carcinoma in 2004].
AB  - This article reviews the available data regarding the acticity of postoperative
      adjuvant systemic therapy for colorectal cancer as first and second-line
      treatment in metastatic disease. The efficacy of adjuvant treatment of patients
      with stage III colorectal cancer is well established. 5-fluorouracil (5-FU) and
      folic acid over 6 months (still) represent todays standard and should serve as
      comparison in randomized studies. The risk of relapse is low in stage II colon
      carcinoma and consequently the efficacy is relatively small compared to stage
      III. New investigation indicate, Capecitabene has the potential to replace 5
      FU/FS as standard treatment for patients with colon cancer. Efficacy results are
      expected to be available in 2004. In metastatic disease combination of 5-FU/folic
      acid plus CPT-11 or OXA are treatment of choice for the first-line therapy of
      metastatic colorectal carcinoma. FOLFOX is high-dose intensity oxaliplatin added
      to the simplified bimonthly leucovorin and 5-fluorouracil regimen as second- line
      therapy for metastatic colorectal cancer. It resulted in prolongation of the
      median progress free survival from 6,8 to 8,8 months and increased the survival
      for 4,5 months. New perspectives are novel chemotherapeutic and targeted agents
      in metastatic colorectal cancer: For the first time, there has been a targeted
      therapy shown convincingly to prolong survival for patients with unresectable
      metastatic colorectal cancer in a well-performed Phase III trial. This agent is
      bevacizumab, a humanised monoclonal antibody targeting the circulating
      proangiogenic growth factor vascular endothelial growth factor. Results with
      bevacizumab should lead to rapid expansion of the number of strategies targeting
      tumour neovasculature. Additionally, an antibody against the epidermal growth
      factor, cetuximab, has been shown to have both single-agent activity and the
      potential ability to partially reverse resistance to a chemotherapy drug. These
      advancements, as well as data on other novel treatment agents that have been
      studied specifically in patients with colorectal neoplasms, are discussed in
      detail.

PMID- 15495754
TI  - [Appropriateness in gastroenterology: too many endoscopies or not enough?].

PMID- 15495752
TI  - [Therapy objectives and daily practice--to which extent are blood sugar target
      values accessible in daily practice?].
AB  - The healthcare sector is characterized at present by increasingly ambitious
      therapeutic objectives and rising healthcare costs. The aim of the Swiss study
      was to explore ways of achieving these therapeutic objectives in the present
      healthcare environment via the use of cost-effective antidiabetic agents. With a
      therapeutic regimen based on gliclazide, it was possible to reduce fasting blood
      glucose levels to below 7.0 mol/l in 70% of the 94 type 2 diabetics included in
      the study. Fasting blood glucose levels returned to normal in 80% of the women
      taking part of the study; the normalization rate was significantly higher in this
      group than in the study population as a whole. The target HbA1c -value was
      attained in 7% of both the patient group receiving gliclazide monotherapy and the
      group receiving gliclazide in combination with metformin. Weight reduction was
      observed in all the treatment groups. Some 86% of the patients experienced an
      improvement in life quality as a result of the more effective management of their
      diabetes. The tolerability of the treatment was very high. A total of two
      episodes of mild symptomatic hypoglycemia were recorded. The per diem costs of
      gliclazide-based treatment are in the range of 1-2 Swiss francs.

PMID- 15495756
TI  - [Versatile St. John's wort].

PMID- 15495755
TI  - [Neuritis of the maxillary nerve. A 55-year-old housewife].

PMID- 15495758
TI  - Collaborative graduate education: executive nurse practice and health care
      leadership.
AB  - Research College of Nursing and the Rockhurst University Helzberg School of
      Management Health Care Initiative collaborated to offer the Executive Nurse
      Practice: Health Care Leadership track to Research College of Nursing graduate
      students. This effort was not only cost effective, but also offered expert
      faculty in both the fields of nursing and business. The curriculum is an
      integration of both fields and faculties from both institutions as they
      communicate and collaborate each semester to successfully coordinate the track.

PMID- 15495759
TI  - Bringing magic to the nursing workforce of the future.
AB  - How can nursing education respond to the ominous signs of a serious shortage of
      nurses in the future? One answer to this question is a focus on reclaiming
      nurses' stories of the "real-world" of nursing practice. In the process of
      creating a childrens book, The Magic Stethoscope, a group of nurse authors found
      a new appreciation for the stories of their practice and the need to share these
      stories with children. The authors hope that these stories will inspire children
      to consider the exciting career opportunities for the nursing workforce of the
      future.

PMID- 15495760
TI  - The Nurse Manager Academy: an innovative approach to managerial competency
      development.
AB  - The quality of nursing leadership has a powerful impact on nurse retention.
      Hospitals that employ effective nursing leaders report increased nursing
      satisfaction, increased group cohesiveness, decreased job stress, and decreased
      turnover (Wells, Roberts, & Medlin, 2002). The Institute for Johns Hopkins
      Nursing has developed a unique training program for nurse managers that employs a
      learner-centered approach and is designed to teach the leadership skills
      essential to successful nursing management. The Nurse Manager Academy prepares
      nurse managers to assume management roles with confidence and competence, making
      them more likely to succeed in one of the most challenging jobs in health care
      today.

PMID- 15495761
TI  - The use of critical reflection in baccalaureate nursing education.
AB  - Leaders in nursing education are incorporating innovative educational strategies,
      including reflection, which will more fully develop student nurses' intellectual
      capacities to conceptualize knowledge to better meet patients' needs (Boud,
      Keough, & Walker, 1998; Duraghee, 1996; Hallett, 1997). This article examines the
      theoretical basis for reflective practice and explores its usefulness in the
      development and transmission of nursing knowledge in baccalaureate nursing
      education. Critical reflection can be effectively utilized by leaders in
      baccalaureate nursing education in classrooms, clinical settings, service
      learning experiences, experiential learning activities, and in the instruction of
      ethical decision-making.

PMID- 15495762
TI  - The process of becoming: from specialty practice to community-based nursing.
AB  - This article reports on the experience of the School of Nursing at Creighton
      University in cross-educating faculty to community-based nursing. In the late
      1990's the Helene Fuld Health Trust recognized the importance of preparing
      nursing faculty for community-based nursing because of changing trends in the
      health care system. Placed in the historical context of the early beginnings of
      nursing practice in the community, this renewed emphasis led to seeking grant
      support from the Trust to strengthen the place of community-based nursing for
      faculty and students alike to be responsive to future changes in health care.

PMID- 15495763
TI  - Presence in three interconnected contexts: considerations for nursing education
      in the 21st century.
AB  - Online nursing education has grown tremendously over the past decade and there is
      every reason to believe that this growth will continue in the 21st century.
      "Presence" is concept that has familiarity in nursing, education, and technology.
      With the convergence of these three interrelated contexts, presence holds a new
      level of interest for nursing education. "Connecting with," "being with," and/or
      "being available" to another in a virtual world poses challenges for nurse
      educators as they turn their focus on student satisfaction in online courses,
      connecting with others in ways that enhance learning, and exploring ways of
      "being with" or "connecting with" patients in both traditional and virtual
      environments of care.

PMID- 15495765
TI  - The role of clinical judgment in professional practice.

PMID- 15495764
TI  - Evidence-based dental advertising.

PMID- 15495766
TI  - [Bronchiolitis obliterans with organizing pneumonia (BOOP). Influenza simulating
      illness with opacity spots in the roentgen image (with no response to
      antibiotics].

PMID- 15495767
TI  - [Valve disease: what the general practicioner needs to know].
AB  - Patients with mitral or aortic valve disease constitute an important part of
      patients in cardiology practice. General practitioners and internists have an
      important role in the long-term care of these patients. We review current
      knowledge and recommendations for follow-up, medical therapy and indications for
      surgery in patients with aortic and mitral valve disease. Asymptomatic patients
      with valve disease need a clinical and echocardiographic follow-up at specific
      time intervals. Most patients with mild or moderate valve disease do not need
      medical or surgical therapy. However, once a patient becomes symptomatic, he
      needs a non-invasive and likely an invasive evaluation for surgical valve repair
      or replacement. In case the valve disease progresses without the development of
      clinical symptoms, the indication for surgery must be derived from hemodynamic
      parameters, the onset of arrhythmias (atrial fibrillation), and pulmonary
      hypertension. In symptomatic and asymptomatic severe valve disease specific
      medical therapy can be very beneficial. However, improvement under medical
      therapy should not delay a prognostically necessary surgical valve repair or
      replacement.

PMID- 15495768
TI  - [Cardiac indications for oral anticoagulation].
AB  - While considering long-term oral anticoagulation one should assess benefit (i.e.,
      reduction in thromboembolic events) and risks (i.e., bleeding complications)
      associated with therapy for each individual patient. The classic cardiac
      indications for oral anticoagulation include chronic atrial fibrillation,
      prosthetic heart valves, and left ventricular thrombus formation following
      anterior myocardial infarction. The value of anticoagulation in patients with
      impaired left ventricular function in stable sinus rhythm and in secondary
      prevention of coronary artery disease remains controversial. For decades warfarin
      has been the only compound available. Currently, promising results have been
      achieved with the oral thrombin inhibitor ximelagatran. In the future, oral
      anticoagulants, which are administered in fixed dose with no need for monitoring
      of the anticoagulation level, may replace warfarin. Safety and efficacy of double
      antiplatelet therapy (aspirin and clopidogrel) in the secondary prevention of
      thromboembolic events in patients with atrial fibrillation are currently being
      addressed in large-scale clinical trials.

PMID- 15495769
TI  - [Vertigo of several seconds duration. 73-year-old pensioned chemical laboratory
      worker].

PMID- 15495770
TI  - [Golden medicinal plant].

PMID- 15495771
TI  - Blanket statement: laundry should be pure and simple.

PMID- 15495772
TI  - See what infection control does.

PMID- 15495773
TI  - When it's said and done: making conference information work for you.

PMID- 15495774
TI  - Understanding ozone.

PMID- 15495775
TI  - Infections: the challenging trolls of transplantation.

PMID- 15495776
TI  - BK virus in kidney transplantation: a case study.
AB  - Prevention as well as treatment of viral infections in transplant recipients
      relies on minimal immunosuppressive therapy consistent with graft survival and
      the use of antiviral therapies in proportion to perceived risk. BK virus creates
      an even greater challenge in posttransplant management and graft survival because
      of difficulty in diagnosing and treatment. BK nephropathy develops in 1% to 5% of
      transplant recipients, with loss of allograft function occurring in 50% of the
      cases. We present a case of a 67-year-old man who developed BK virus allograft
      nephropathy 9.5 months after transplantation. His allograft function was extended
      through rigorous treatment with an antiviral agent, reduction of
      immunosuppressant, and monitoring in an outpatient setting.

PMID- 15495777
TI  - Nonprescription analgesics and their use in solid-organ transplantation: a
      review.
AB  - OBJECTIVE: To review the pharmacology, adverse events, drug interactions, and use
      of the nonprescription analgesics in solid-organ transplant recipients. STUDY
      SELECTION AND DATA EXTRACTION: Studies evaluating nonprescription analgesics in
      solid-organ transplantation were considered for evaluation. English-language
      studies were selected for inclusion. DATA SYNTHESIS: Nonprescription analgesics
      (aspirin, choline salicylate, magnesium salicylate, sodium salicylate, ibuprofen,
      ketoprofen, naproxen sodium, and acetaminophen) are the most commonly purchased
      over-the-counter agents in the United States. These agents, although generally
      considered safe, have been associated with a number of toxicities. The
      salicylates and nonsteroidal anti-inflammatory drugs have been associated with
      gastrointestinal damage, hematologic changes, liver and kidney dysfunction, and
      breathing difficulties. Acetaminophen has been shown to induce hematologic
      changes and liver and renal dysfunction. CONCLUSION: A closer look at the
      nonprescription analgesics reveals their potential for harm when used by solid
      organ transplant recipients. In this patient population, the salicylates and
      nonsteroidal anti-inflammatory drugs should generally be avoided if possible,
      because of their potential toxicities, especially renal dysfunction. Low-dose
      aspirin, for the prevention of cardiovascular and cardiocerebral events, appears
      to be safe, but patients must still be followed closely. Acetaminophen is
      generally considered the nonprescription analgesic and antipyretic of choice in
      transplant recipients because of its favorable toxicity profile. However, it is
      imperative that patients and transplant practitioners are aware that this agent
      is not without toxicities and proper monitoring is advised.

PMID- 15495778
TI  - Posttransplant malignancy.
AB  - In the past few decades, great advances have been made in the field of solid
      organ transplantation. A greater understanding of immune system function, the
      development of modern immunosuppression, and advancements in surgical technique
      have led to marked improvements in both recipient and graft survivals, as well as
      recipients' quality of life. However, improved survival rates have also led to
      prolonged exposure to chronic immunosuppression, which increases the risk for the
      development of posttransplant malignancies. In addition, older transplant
      candidates are being considered, carrying with them the increased likelihood of
      preexisting malignancy. Consequently, the potential risk of posttransplant
      malignancy must be considered. Moreover, as long-term transplant survivors
      continue to age, posttransplant malignancies will be seen more frequently. This
      review presents the more commonly encountered posttransplant malignancies and the
      measures that are currently being utilized to prevent and treat them.

PMID- 15495779
TI  - Living kidney donor decision making: state of the science and directions for
      future research.
AB  - BACKGROUND: The Federal government and transplantation organizations have called
      for further study of living donation at a time when 3 new living donor protocols
      are being introduced throughout the United States that promise to significantly
      increase the donor pool and change the face of living donation. Donation to a
      once incompatible and sometimes unknown recipient may now occur through the use
      of plasmapheresis therapy or paired and nondirected living donor protocols.
      OBJECTIVE: To describe the state of the science on living kidney donor decision
      making, and to provide recommendations for future research to guide donor
      education and care. DATA SOURCES: Automated literature search using PubMed and
      CINAHL scientific literature databases. STUDY DATA EXTRACTION: Research papers on
      living donor decision making from 1997 to 2003. Studies available only as
      abstracts were excluded. DATA SYNTHESIS: Studies of living kidney donor decision
      making and outcomes have been limited in scope, with small sample sizes and
      inconsistent reports of racial and ethnic characteristics of the sample. The
      retrospective nature of the majority of living donor studies is a significant
      limitation. CONCLUSIONS: Future prospective studies that are diverse by sex,
      race, and ethnicity will contribute to our knowledge of factors that influence
      the decision to be a living kidney donor.

PMID- 15495780
TI  - Evaluation of an immunosuppressant side effect instrument.
AB  - BACKGROUND: Clinicians continue to be compelled to evaluate the impact of
      immunosuppressive medication side effects on the quality of life of transplant
      recipients. We Were asked to develop an instrument to measure side effects in
      immunosuppressed transplant recipients. OBJECTIVE: To construct an instrument
      that measures the impact and severity of side effects of immunosuppressive
      medications used in transplantation and to assess the reliability and validity of
      the newly developed instrument called the Memphis Survey. DESIGN: The instrument
      was constructed by a panel of physicians, nurses, and pharmacists with experience
      in treating transplant recipients. A small group of kidney transplant recipients
      (n= 13) provided pilot data for refining and testing the instrument. A national
      sample of kidney, liver, and heart transplant recipients (n = 505) provided data
      that were used to further develop the instrument. ANALYSIS: Factor analysis was
      used to determine the psychological dimensions underlying the instrument and to
      guide the construction of scales from the survey items. The instrument scales
      were then computed from the dataset of 505 transplant recipients to quantify the
      impact of immunosuppressant side effects on the quality of life of transplant
      recipients. RESULTS AND CONCLUSION: Analyses showed the final instrument scales
      to be valid and reliable. Exploratory analysis suggests the need for further
      testing of the instrument to determine gender differences.

PMID- 15495781
TI  - Shopping for a transplant: when noncompliant patients seek wait listing at
      multiple hospitals.
AB  - United Network for Organ Sharing policy allows patients to be listed for a
      transplant at multiple hospitals. This strategy can sometimes lessen the
      transplant waiting time for patients because waiting times vary geographically.
      We explore the ethical dilemma of "shopping for a transplant" by presenting the
      case of a patient with an addictive disorder who was listed for liver
      transplantation at one hospital on the east coast of the United States and was
      seeking listing at 2 additional hospitals in midwestern United States, when
      marijuana use was suspected by 1 of the latter 2 facilities. Although the
      transplant team at this facility deferred listing the patient, the team's
      bioethicist posed the concept of a duty to notify the facility where the patient
      was already listed for transplantation about any confirmed substance abuse, in an
      effort to prevent a scarce resource from being allocated to an individual who is
      noncompliant.

PMID- 15495782
TI  - Appraisal and coping as predictors of psychological distress and self-reported
      physical disability before lung transplantation.
AB  - CONTEXT: Certain appraisals and coping strategies have been associated with
      increased levels of psychological distress and disability in other medical
      populations, but no study has examined this relationship with patients who are
      awaiting lung transplantation. OBJECTIVE: To describe the cognitive appraisal and
      coping strategies used by patients who are pursuing lung transplantation and to
      evaluate the extent to which these processes are associated with depression,
      anxiety, and disability. METHODS: This is a cross-sectional design with 160
      participants (42.5% men) who have end-stage lung disease and were evaluated for
      lung transplantation at a large medical center. MEASURES: The outcome variables
      of depression, anxiety, and physical disability were assessed using the Beck
      Depression Inventory, Spielberger Trait Anxiety Inventory, and the Sickness
      Impact Profile, respectively. The predictor variables, coping and appraisal
      styles, were measured using the COPE and the Stress Threat Questionnaire,
      respectively. Demographic variables were also assessed. RESULTS: Patients used a
      variety of adaptive problem- and emotion-focused coping strategies. Hierarchical
      multiple regressions demonstrated that harm appraisals and the use of particular
      types of coping styles; namely, disengagement, avoidance, ruminating and venting
      emotions, low solicitation of emotional support, and suppressing other activities
      are maladaptive and were uniquely related to psychological distress and
      disability. CONCLUSIONS: Maladaptive appraisal and coping styles can serve as
      markers of emotional distress and disability that may help the transplant team
      identify patients who may benefit from counseling and psychological
      interventions.

PMID- 15495783
TI  - Potential living kidney donors' health education use and comfort with donation.
AB  - CONTEXT: Much living kidney donation research focuses on actual donors rather
      than all donors who are evaluated by the transplant center. OBJECTIVE: To
      determine (1) what concerns and benefits potential donors saw possible from
      donation, (2) how they educated themselves before contacting the transplant
      center, and (3) who were the most comfortable donors. DESIGN: A telephone survey
      of 91 potential donors before transplant evaluation. SETTING: Barnes-Jewish
      Hospital Transplant Center in St Louis, Mo. MAIN OUTCOME MEASURES: Willingness
      and comfort donating, key concerns and perceived benefits to donation, hours of
      transplant-related education. RESULTS: On a 7-point scale, potential donors were
      very willing (mean=6.65, SD=0.95) and comfortable (mean=6.31, SD= 1.12) donating.
      They were most concerned that their recipients would die if they could not
      donate, the evaluation and surgery would be anxiety provoking or painful, and
      they did not understand what donation would require. Donors previously spent an
      average of 6 hours reading health resources and 32 hours discussing donation.
      Using logistic regression, those donors with 0 to 4 concerns (odds ratio=7.1, 95%
      confidence interval [CI], 2.2-23.16), more than 5 benefits (odds ratio=3.7, 95%
      CI, 1.2-11.0), and who were family members (odds ratio=4.7, 95% CI, 1.4-15.8)
      were more likely to be extremely comfortable donating compared to others.
      CONCLUSIONS: Before evaluation, most potential donors are willing to donate
      because they think that it is important to improve the health of a loved one.
      Their knowledge of donation varies and they need clear information about medical
      testing and support coping with any negative donation outcomes.

PMID- 15495784
TI  - Factors during donor care that may affect liver transplantation outcome.
AB  - Publications are reviewed that identify factors during donor care and
      characteristics of the donor liver that may be associated with outcome following
      liver transplantation. The procurement coordinator has the opportunity to
      influence cold ischemia time, blood pressure, the serum sodium concentration and,
      perhaps, liver glycogen reserves. These variables may significantly affect
      postimplantation graft performance and graft or recipient survival. Summaries of
      those publications comprising this database are presented, and several
      limitations in their interpretation are discussed.

PMID- 15495785
TI  - Increasing organ recovery from level I trauma centers: the in-house coordinator
      intervention.
AB  - PURPOSE: Daily presence of organ procurement organization staff in level I trauma
      centers combined with early family contact and interaction can increase donation
      rates. METHODS: A successful in-house coordinator program already in place at 2
      level I trauma centers in Houston was replicated in 6 other level I trauma
      centers in New York City, Los Angeles, and Seattle. Organ procurement
      organization staff were placed inside the 8 trauma centers to provide early
      family support in potential donor situations and day-to-day donation system
      management. Comparison data were obtained on 83 level I trauma centers
      nationally. Data from 1999 to 2000 were compared with data from 2001 to 2002.
      RESULTS: Despite demographic differences, the 8 centers with in-house
      coordinators had higher consent rates (60% vs 53%) and conversion rates (55% vs
      45%) than centers without them. Conversion of potential to actual donors was 22%
      higher in centers with in-house coordinators than in centers without them.
      Donation rates were affected by donor age, ethnicity, previous family discussion
      of donation, the family's initial reaction to the request (favorable,
      unfavorable, undecided), amount of time family spent with the in-house
      coordinator, presence of the in-house coordinator during explanation of brain
      death, whether the request was made at the same time as the brain-death
      explanation, and, in cases where donation was mentioned to the family before the
      formal request, who first mentioned donation to the family. CONCLUSIONS: In-house
      coordinators improve the donation process by interacting with families and staff
      earlier and more often during potential organ donations and improving donation
      systems through closer relationships with hospital staff.

PMID- 15495786
TI  - Circulating ICAM-1, VCAM-1, E-selectin, P-selectin, and TNFRII in patients with
      coronary artery disease.
AB  - OBJECTIVE: To evaluate the relationship between the serum concentration of tumor
      necrosis factor receptor 2 (TNFRII) and some adhesion molecules [including
      intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1
      (VCAM-1), P-Selectin, and E-Selectin] and coronary artery stenosis. DESIGN AND
      SETTING: Observational (cross-sectional) study in a University Heart Hospital in
      Tehran, Iran. PATIENTS: 75 patients with angiographically proven coronary artery
      disease were compared with 81 individuals who had undergone coronary angiography
      with no significant evidence of stenosis (control subjects). METHODS: Soluble
      adhesion molecules and TNFRII were determined by enzyme-linked immunosorbent
      assay technique. sICAM-1 and sP-selectin values were significantly higher in
      patients with coronary artery disease than in control subjects [146(38) vs.
      132(48) p < 0.04 and 275(107) vs. 241(104) ng/ml p < 0.04 respectively]. Multiple
      logistic regression analysis showed sICAM-1 an independent discriminating risk
      factor for coronary artery disease (p < 0.03). Prediction models that
      incorporated sICAM-1 in addition to other established coronary risk factors were
      significantly better at predicting risk than the models based on the other risk
      factors alone. Multiple regression analysis indicated that sP-selectin levels
      were greater in patients with single-vessel disease than in the respective normal
      (p < 0.01). CONCLUSIONS: Our findings suggest that sICAM-1 has an association
      with s1 coronary artery disease as such; the evaluation of this marker may
      improve the coronary risk assessment in Iranian patients.

PMID- 15495787
TI  - Proinflammatory cytokine profile in active kidney tuberculosis patients.
AB  - INTRODUCTION: Mycobacterium tuberculosis is a facultative intracellular pathogen
      that developes specific T cell response expressed by the production of IL-12, IFN
      gamma, and TNF-alpha. The response has been quite well investigated in the
      experimental models, however, there is little information about certain cytokine
      levels in patients with extrapulmonary tuberculosis. The shortage of data
      pertains also to its most common form-kidney tuberculosis, especially when
      bacilli dissemination into the blood circulation has occurred. OBJECTIVES: The
      aim of our study was to examine simultaneously the frequency of Mycobacterium
      tuberculosis presence in the blood circulation and the serum cytokine
      concentration during kidney tuberculosis to approach their relationship in the
      clinical infection process. It is considered that cytokine levels do not
      correlate with localisation of tuberculosis (pulmonary vs. extrapulmonary),
      however, there is little information about the cytokine levels in patients with
      kidney tuberculosis. MATERIALS AND METHODS: 30 patients attending the urology
      clinic with suspicion of kidney tuberculosis were evaluated. Serum concentrations
      of selected cytokines in patients with urine, urine and blood Mycobacterium
      tuberculosis presence were quantified by ELISA and compared to PCR negative
      patient and group of healthy people. RESULTS: Our study demonstrates the increase
      of TNF-alpha and IL-12 level in comparison to control group. TNF-alpha
      concentration was about 2-fold higher in the positive patients than it was in
      control group; IL-12 concentration was about 4-fold higher and the differences
      between IL-12 levels were statistically important (p < 0.05). However, no
      significant differences were found in IFN-gamma level among all groups. Using
      Spearman correlation rank test, a significant correlation was found between TNF
      alpha and IL-12 in the positive patient group. The correlation factor was more
      significant for the group of patients with Mycobacterium tuberculosis present in
      blood and urine than it was in urine positive PCR group (r = -0.66 vs. r = 
      0.51).

PMID- 15495788
TI  - Effect of L-arginine on age-related changes in macrophage phagocytic activity.
AB  - Aging is associated with decline in the functioning of immune cells and
      reductions in serum L-arginine and excretion of nitric oxide metabolites. Studies
      have shown that L-arginine plays an important role in many physiological,
      biological and immunological processes. The present study was performed to
      determine if treatment with L-arginine could prevent age-related changes in
      phagocytic function of peritoneal macrophages. The effects of L-arginine on
      phagocytic activity of peritoneal macrophages were compared between young and
      middle-aged rats. Studies were performed in four groups of rats for 8 weeks:
      group 1 (3 month-old) received physiological saline; group 2 (3 month-old)
      received L-arginine (160 mg/kg/day); group 3 (12 month-old) received
      physiological saline; group 4 (12 month-old) received L-arginine (160 mg/kg/day).
      There were no significant differences in percentage of cells which were
      phagocytized. However, the phagocytosis of activated charcoal by peritoneal
      macrophages reduced with age. Thus, the phagocytic index was lower in macrophages
      of middle-aged rats. L-arginine treatment increased phagocytosis by peritoneal
      macrophages of both young and middle-aged rats. L-arginine-induced augmentation
      in phagocytosis by macrophages were much higher in the middle-aged rats compared
      with young rats. In summary, we found that L-arginine prevented the age-related
      reduction in phagocytic capability of peritoneal macrophages.

PMID- 15495789
TI  - Polyphenolic antioxidants enhance IgE production.
AB  - Epidemiological data showed that total IgE and IL-4 levels in cigarette smokers
      were elevated, comparable to those in the asthmatics. The etiological agent(s)
      elevating IgE production are not clear. We evaluate whether tobacco polyphenols
      potentiate IgE production in a rodent model. Mice were fed with rutin or CGA in
      drinking water during antigen sensitization, followed by antigenic challenge i.p.
      in alum. CGA and rutin were also delivered in a bolus intraperitoneally or
      intranasally along with antigens during immunization. Antigen-specific IgE and
      IgG responses were measured. Enhancement of total IgE responses via i.p. and
      drinking routes can be achieved at concentrations as low as 0.1% CGA.
      Furthermore, IgG1 responses but not IgG2a and IgG2b were augmented, indicating a
      Th2 type of response by CGA. Moreover, both antigen-specific and serum IgE
      production can be achieved when CGA and antigenic challenges were delivered
      intranasally in the absence of alum. In contrast, nicotine does not enhance
      antigen-specific IgE production, and only marginally affects serum IgE levels.
      The more polarized Th2 development in CGA-treated mice may account for
      enhancement of both antigen-specific and total IgE responses. High levels of IL-4
      but not IFN-gamma or IL-12, were observed in antigen-challenged mesenteric lymph
      nodes (MLN) cultures from CGA-treated mice. In contrast, significant levels of IL
      4, IL-12, and IFN-gamma were observed in antigen-challenged cultures from
      nicotine-treated mice. This study shows that tobacco polyphenols, CGA and rutin
      potentiated IgE production in vivo. Polyphenolic antioxidants enhance Th2
      development. We propose that IgE production and T cell dichotomy may be
      critically influenced by the redox microenvironment. Enhanced Th2 development and
      IgE production henceforth may counteract more severe Th1-mediated tissue damage
      triggered by environmental oxidative stress.

PMID- 15495790
TI  - Multiparameter flow cytometric approach for simultaneous evaluation of
      proliferation and cytokine-secreting activity in T cells responding to allo
      stimulation.
AB  - We report a method combining mixed lymphocyte reaction (MLR) using a
      carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeling technique,
      intracellular cytokine immunofluorescence staining (ICIS), and multiparameter
      flow cytometry for simultaneous determination of proliferation and cytokine
      secreting activity in T cells responding to allo-stimulation. C57BL/6 (B6) mice
      and Balb/c mice were used in the experiments. CFSE-labeled responder splenocytes
      were cultured with irradiated stimulator splenocytes, followed by ICIS. In both
      the Balb/c stimulator-versus-B6 responder (Balb/c-vs.-B6) and the B6-vs.-Balb/c
      allogeneic combinations, interleukin (IL)-2 secreting cells and interferon (IFN)
      gamma secreting cells were identified predominantly in proliferating CD4+ and
      CD8+ T cell fractions, respectively. The suitability of this method was proven by
      demonstrating a close relationship between the values of cytokines in culture
      supernatants (that were determined by Cytometric Bead Array assay) and indexes
      for cytokine-production (that were obtained by multiplying the percentage of
      cytokine-producing cells in T cells and mean fluorescence intensity of cytokine
      staining determined by the combined MLR and ICIS).

PMID- 15495791
TI  - Double diffusion in gel reactions with antigens insoluble in aqueous media.
AB  - Ethanol-soluble, but saline-insoluble antigens were prepared as saline
      suspensions and studied in double diffusion reactions in a soft agarose gel.
      Positive reactions were observed with syphilis and SLE sera tested against the
      Kahn antigen as well as against commercial cardiolipin reagents. Also, ethanol
      soluble brain antigen was studied for organ-specific reactions with rabbit immune
      sera. It was shown that double diffusion in gel can be employed as an analytical
      procedure for studies on reactions of saline suspensions of ethanol-soluble
      antigens.

PMID- 15495792
TI  - Expression of neutral glycosphingolipids in the brain and spleen of mice lacking
      TNF receptor 1.
AB  - We investigated the expression of neutral glycosphingolipids (GSLs) in the brain
      and spleen of mice lacking the gene for the tumor necrosis factor-alpha receptor
      p55 (TNFR1). Neutral GSLs of the ganglio-, globo-, and neolacto-series were
      determined in the tissues of homozygous (TNFR1-/-) and control heterozygous
      (TNFR1+/-) animals by high performance thin layer chromatography (HPTLC) overlay
      immunostaining with specific antibodies. The spleen of homozygous TNFR1 knockout
      mice lacked glucosylceramide substituted with palmitic acid, GlcCer(C16), and
      showed severe reduction in the expression of GlcCer(C24). In addition,
      gangliotetraosylceramide substituted with palmitic acid, Gg4Cer(C16), and
      globotetraosylceramide, Gb4Cer, were down-regulated in the TNFR1-/- spleen in
      comparison with the heterozygous control. The brain of both groups of animals
      (TNFR1-/- and TNFR1+/-) did not express detectable levels of Gg4Cer, Gb5Cer and
      Gb4Cer, but the brain of TNFR1 knockout mice expressed abundant
      globotriaosylceramide, Gb3Cer, compared to no expression in control heterozygous
      mice. nLcCer(C24) had slightly higher (1.4 fold) expression in the brain of TNFR1
      /- mice compared with the control animals. This study provides in vivo evidence
      that TNF signaling via the TNFR1 is involved in the acquisition of a divergent
      GSL assembly in the brain, an immunologically privileged organ, and the spleen,
      typical secondary lymphoid organ.

PMID- 15495793
TI  - The immunosuppressive effect of methotrexate in active rheumatoid arthritis
      patients vs. its stimulatory effect in nonactive patients, as indicated by
      cytometric measurements of CD4+ T cell subpopulations.
AB  - This cytometric study assesses the effects of methotrexate (MTX) on the expanded
      CD4+ lymphocyte population in active and nonactive rheumatoid arthritis (RA)
      patients. In the active patients, MTX was found to reduce the predominant CD4+
      CD28+ subpopulation (by 30%), and the minor subpopulation of CD4+ CD28- (by 34%).
      The incidence of CD25 phenotype was downregulated by 15%. These reductions can be
      attributed to immunosuppression through apoptosis, which was demonstrated by MTX
      induced fluorescein diacetate (FDA) hyperpolarization (an established indicator
      of early apoptosis). In contrast, in nonactive RA patients, the major CD4+ CD28+
      subpopulation of small lymphocytes appeared to be activated by MTX, subsequently
      transforming into a major hyperblast population, whereas the minor CD4+ CD28-
      subpopulation was not affected by MTX treatment. The activation by MTX in this
      group of patients is evidenced by MTX-induced FDA depolarization (an indicator of
      early activation). Thus, MTX immunosuppressive effect on CD4+ subsets was found
      in active patients, whereas immunostimulation by MTX was shown in nonactive
      patients. The found discriminative effect of MTX may suggest a higher
      effectiveness of low-dose MTX therapy in active RA patients.

PMID- 15495794
TI  - Collaboration and social inquiry: multiple meanings of a construct and its role
      in creating useful and valid knowledge.
AB  - The concept of collaboration in community research and intervention, although not
      new, has grown tremendously in importance in the past 20 years. Yet, it is both a
      contested concept in terms of its intent and a still evolving idea in terms of
      its meaning and implications. The purpose of this monograph is to begin to
      "unpack" the collaboration construct in terms of its many meanings, rationales,
      goals, models, dynamics, and accomplishments. Although models of collaboration
      are often well articulated there is "partial paradigm acquisition" (E. J.
      Trickett, 1984) in terms of understanding their behavioral and ethical
      implications. There is more theology than conclusion. The promise of
      collaboration, although considerable, is still in need of multiple and varied
      empirical examples of how collaboration contributes to both the process and goals
      of community research and intervention, however defined. The monograph closes
      with a brief overview of what we have learned from reviewing this literature, an
      articulation of the kinds of questions that need to be addressed, and a series of
      recommendations for how to increase our understanding of the collaboration
      construct in community research and intervention.

PMID- 15495795
TI  - Racial identity, parental support, and alcohol use in a sample of academically at
      risk African American high school students.
AB  - This study examined racial identity and parental support as predictors of alcohol
      use in a sample of 488 African American adolescents. Two dimensions of racial
      identity were investigated: (1) racial centrality (i.e., the significance that
      one places on race in defining oneself) and (2) private regard (i.e., the extent
      to which one feels positively about Black people). In addition, perceived support
      from mothers and fathers was examined. Multivariate results showed that private
      regard and father support were associated with less self-reported alcohol use
      after partialling out the effects of age and gender. An interaction between the
      two racial identity dimensions was also found such that private regard was
      associated with less alcohol use for adolescents who reported that race was a
      more central part of their identity.

PMID- 15495796
TI  - Revisiting Hispanic adolescents' resilience to the effects of parental problem
      drinking and life stress.
AB  - Two previous studies found that life stress and parental alcoholism were not as
      highly related to distress for Hispanic adolescents as they were for European
      American adolescents (M. Barrera Jr., S. A. Li, and L. Chassin, 1993, 1995).
      Those findings could be interpreted as evidence of Hispanic youths' resilience,
      but limitations of the stress measure and the homogeneity of the Hispanic sample
      threatened this interpretation. The present study improved on those previous
      studies by using a new measure of uncontrollable stressors and a more
      heterogeneous Mexican American sample. Participants in this study were 175
      Mexican American and 59 European American adolescents and their parents. Unlike
      the previous studies, results did not show that Mexican American adolescents were
      more resilient to parental problem drinking or life stress than were European
      American adolescents. Overall, life stress was related to adolescents', mothers',
      and fathers' reports of adolescents' psychological distress above and beyond the
      effects of ethnicity and socioeconomic factors.

PMID- 15495797
TI  - The social networks of women experiencing domestic violence.
AB  - The research literature has demonstrated that battered women living in shelters
      experience impaired social support. This study examines this phenomenon among
      battered women living in the community. This study compared a group of pregnant
      battered women (n = 145) and a group of pregnant nonbattered women (n = 58) in
      terms of their structural [e.g., total number of supporters, network members in
      violent relationships with their partners (an index of homophily or nonhomophily)
      and functional (e.g., emotional)] social support. Four reasons for impaired
      support in battered women were proposed and examined, including social isolation,
      failure to disclose abuse, homophily, and low SES. Only homophily was related to
      impaired support among battered women. In addition, the relationship between
      structural and functional support and mental health outcomes (e.g., depression,
      self-esteem) was examined. Criticism, practical support, homophily, and
      disclosure were all significant predictors of mental health for battered women.
      Implications for community-based interventions are discussed in the context of
      current intervention strategies with battered women.

PMID- 15495798
TI  - Facilitators and inhibitors of positive school feelings: an exploratory study.
AB  - This paper brings together the educational psychology and place experience
      literatures to explore 8 children's experiences of school behavior settings.
      Within this framework, the goal is to think of school as a place comprised of
      multiple behavior settings, disentangle behavior and engagement, and problematize
      the construct of engagement. Results indicate that children liked places where
      the physical space was open, and they had some autonomy, independence, choice,
      opportunities for leadership, and social support. Conversely, they disliked
      places that were physically chaotic, where they perceived an abuse of power, and
      that inhibited choice, independence, and autonomy. Finally, children engaged
      their disliked places by attempting to personalize these spaces to bring in other
      parts of their identities. Implications include creating behavior settings that
      lead to positive experiences, attending to social justice, and the use of project
      based pedagogies.

PMID- 15495799
TI  - Beyond the individual: toward a nomological network of organizational
      empowerment.
AB  - Empowerment research has generally been limited to the individual level of
      analysis. Efforts to study empowerment beyond the individual require conceptual
      frameworks suggesting attributes that define the construct and guide its
      measurement. This paper presents an initial attempt to describe the nomological
      network of empowerment at the organizational level of analysis--organizational
      empowerment (OE). Intraorganizational, interorganizational, and
      extraorganizational components of OE are described. Implications for empowerment
      theory and practice are discussed.

PMID- 15495800
TI  - Abuse experiences in a community sample of young adults: relations with
      psychiatric disorders, sexual risk behaviors, and sexually transmitted diseases.
AB  - This study documents significant associations among lifetime abuse experiences,
      psychiatric diagnoses, and sexual risk behaviors in a multiethnic community
      sample of young men and women (N = 1803) in South Florida. Self-report data were
      collected via structured interviews as part of a longitudinal follow-up of a
      larger school-based study. Participants were grouped according to extent of
      lifetime abuse experiences. Cumulative lifetime abuse experiences were associated
      with increased risk for a broad range of individual lifetime psychiatric
      disorders, as well as cumulative lifetime psychiatric disorders. Both cumulative
      abuse experiences and cumulative psychiatric disorders were independently
      associated with (a) higher levels of sexual risk behaviors and (b) higher risk
      for lifetime sexually transmitted diseases (STDs). Implications for selective
      prevention of sexual risk behaviors and STDs among young adults with histories of
      abuse and psychiatric disorders are discussed.

PMID- 15495801
TI  - [Study on the changes of electrocardiogram and ultrastructural in heroin
      dependence in rats].
AB  - OBJECTIVE: To study the changes of electrocardiograms (ECG) and myocardial
      ultrastructure in heroin dependence in rats, in order to reveal the mechanisms of
      the myocardial injury by heroin. METHODS: Establish heroin addict model in SD
      mice, investigate the changes in electrocardiograms, HE staining and myocardial
      ultrastructure. RESULTS: The electrocardiograms of the addict group had
      prominently changes, main expressions: heart rate decreased, P wave and T wave
      amplitude reduced and duration increased, S-T reduced and duration increased, QT
      interval prolongation, these changes indicated that myocardium had been injured,
      myocardial ischemia, ventricle function declined. These difference was
      significant (P<0.05) between before inject heroin and after inject heroin.
      Transformations in the ultrastructure: nuclear concentrate, reduce, nuclear
      membrane shrink, chromatin agglutinate, mitochondria cristal had disorder
      formation, disappeared or hollowed, these indicated that heroin could cause
      pathological changes in myocardial ultrastructure. CONCLUSION: Above-mentioned
      changes indicated that heroin can injure myocardium, and the changes of
      myocardial ultrastructure suggested that myocardial apoptosis may be one of the
      mechanisms of the myocardial injury by heroin.

PMID- 15495802
TI  - [The study of the major sarcosaphagous flies in Hohhot].
AB  - OBJECTIVE: In order to determine the major species of sarcosaphagous flies and
      their regular activity on carcass in Hohhot district. METHODS: Six rabbits were
      killed and placed outdoors at different time from July to October in Hohhot
      district. Some species of sarcosaphagous flies that appeared the cadavers were
      observed and identified. RESULTS: It showed that there are 10 main spieces
      belonging to 3 families and 8 genera were from Diptera, including Musa domestica
      domestica Linnaeus, Musa domestica vicina Maequart, Ophyra capensis (Wiedemann),
      Hydrotaea armipes (Fall.), Muscina stabulans (Fall.) from Museidae; Lucilia
      sericata (Meigen), Chrysomya megacephala (Fabricius), Lucilia cuprina (Wiedemann)
      from Calliphoridae; Boettcherisca peregrina (Robineau-Desvoiy), Parascarcophaga
      crassipalpis (Maequart) from Sacrophagidae. Besides, it showed obvious
      regulations that different species of sarcosaphagous flies appeared on carcass at
      different postmortem interval and the first part of carcass that sarcosaphagous
      flies appeared on. CONCLUSION: It may be useful for estimating postmortem
      interval in Hohhot district.

PMID- 15495803
TI  - [Immunohistochemical study of Cx43 dephosphorylation in human left ventricular
      myocardium suffered by acute ischemia].
AB  - OBJECTIVE: This study was performed to detect the phosphorylation state of Cx43
      in human left ventricular myocardium among sudden deaths caused by acute
      myocardial ischemia (AMI) especially sudden coronary death (SCD) and control
      groups. And then evaluate the significance of these findings in diagnosing the
      early pathological changes of acute myocardial ischemia. METHODS:
      Immunohistochemistry (IHC) SP techniques were adopted to detect the
      phosphorylation state of Cx43 in the left ventricular myocardium samples of 45
      deceased, which classified as group I--SCD, group II & III (other two groups of
      AMI) and Group IV & V (two control groups, sudden death caused by lethal acute
      cranio-cerebral injury or pathologic intracranial hemorrhage). In addition, we
      selected anti-Pan-Cadherin (construction protein of adherent junctions on the
      intercalated disc) and PHA-E+L/Bio, to detect the integration of myocardial
      mechanical coupling and membranes (applying affinityhistochemistry, AHC)
      respectively. RESULTS: (1) Phosphorylated Cx43 positive staining was almost
      invisible in Group I, II and III or scattered in sarcoplasm in few samples; but
      it was assembling at the IDs clearly in group IV and V. (2) Strongly positive
      staining of Pan-Cadherin could be observed at the IDs and (3) integrated
      myocardial membranes were found in all samples. CONCLUSION: These findings
      suggested that compared with the control groups, the integration of myocardial
      mechanical coupling and membranes did not alter in AMI. But Cx43, the key protein
      of electrical coupling on myocardial gap junctions, occurred dephosphorylation
      remarkably in AMI. Thus applying IHC techniques to detect the Cx43
      dephosphorylation in human left ventricular myocardium maybe useful to recognize
      the onset of arrhythmia in AMI, especially in SCD whose myocardium without
      apparent morphological changes.

PMID- 15495804
TI  - [Study on relationship between changes of geometry parameters in human spleen
      nuclei and the postmortem interval].
AB  - OBJECTIVE: Using computer image-analyze technique (CIAT) to study changes of
      geometry parameters in human spleen nuclei and seek a new experimental method to
      deduce the estimation the postmortem interval (PMI). METHODS: 31 cadavers that
      known accurate PMI, sampled and smeared respectively every hour within the first
      36 hours after death, fixed with cold Carony fixation, stained by Feulgen-van's
      method, and measured 5 geometry parameters using the image-analyze instrument
      including Area (A), Mean-Dia (MD), Average Diameter (AD), perimeter (P), Index of
      density (ID). RESULTS: A, MD, AD and P in the human spleen nuclei have no
      correlation with the PMI. But ID rose regularly with the prolongation of PMI in
      36 hours. There was a definite correlation between ID and the PMI, r=0.983,
      linear regression equation with PMI (hours) as the dependent variable was
      calculated for ID. CONCLUSION: Geometry parameter ID was proved to be preferable
      indexes for estimation of PMI in 36 hours.

PMID- 15495805
TI  - [Concentration changes of amylase in vitreous humor of acute pancreatitis
      associated with different postmortem interval in rabbits].
AB  - OBJECTIVE: To investigate concentration changes of amylase in rabbits vitreous
      humor of acute pancreatitis associated with postmortem different interval.
      METHODS: To induce animal model of acute pancreatitis with sodium taurocholate,
      observed concentration changes of amylase after different postmortem interval,
      then compared with normal. RESULTS: The concentration of amylase in vitreous
      humor of rabbit 24h after death were related to postmortem interval
      significantly; The concluded formulae of the relationship between postmortem
      interval and amylase concentration is y=8.7420+0.7699x-0.0083x2 (R2=92.62792,
      F=14.89734, P=0.001). CONCLUSION: Concentration changes of amylase in vitreous
      humor of acute pancreatitis associated with postmortem interval may provide a new
      sensitive and objective method for the forensic early injury time estimation.

PMID- 15495806
TI  - [Identification of grades division to diminished criminal responsibility in
      mental disorder offender].
AB  - OBJECTIVE: To explore the basis to discriminate diminished criminal
      responsibility. METHODS: Chi-square test, one-way ANOVA test, factor analysis and
      stepwise discriminant analyses were conducted for 92 cases which were divided
      into three groups according to the degree of diminished criminal responsibility.
      RESULTS: There were significant differences in the type of crime and rating score
      among three groups. The factor 1 reflecting the premeditation and preparation
      before crime was the most important of all factors. Realistic motivation, time
      selectivity of offending, emotion during the crime, understanding the nature of
      the behavioral, impairment of life ability and impairment of reality testing were
      the discriminating factors of grades division in diminished criminal
      responsibility. CONCLUSION: The diminished criminal responsibility in mental
      disorder offender could be divided into three grades.

PMID- 15495807
TI  - [The creation of an instrument to determine competency to stand trial].
AB  - OBJECTIVE: To create an instrument to determine the mental disorder offenders'
      competency to stand trial, which is according with the Chinese legal system.
      METHODS: Integrating the foreign instruments and the Chinese criminal
      jurisprudence, and combing the authors' forensic psychiatric experience, the
      research team created an instrument which was called Competency to stand trial
      Determining Instrument firstly, then used the instrument in practice, in the end
      the validity and reliability of the instrument were inspected, and through an
      diagnostic test, the feasibility of the instrument was evaluated. RESULTS: Split
      half and homogeneity reliability of the instrument is 0.9366 and 0.9213
      respectively, the correspondence of the conclusion between the instrument and the
      expertise is 0.704. Except the sensitivity is 0.6097, all the other diagnostic
      index are over 0.80. CONCLUSION: The Competency to stand trial Determining
      Instrument is feasible.

PMID- 15495808
TI  - [A study of mental health issues in the objects of substance abstinence who got
      labor education and rehabilitation].
AB  - OBJECTIVE: To investigate the personality and mental health of the objects of
      substance (caffeine, cocaine, hallucinogens and so on) abstinence who got labor
      education and rehabilitation. METHODS: 258 male objects and 250 female objects of
      substance abstinence selected randomly from institutions of labor education and
      rehabilitation were assessed with MMPI and SCL-90. RESULTS: MMPI tests indicated
      the personality abnormality in the objects. SCL-90 tests manifested the mental
      health abnormality of them compared with Chinese models, especially in the female
      objects. CONCLUSION: More attention should be paid on the mental health of the
      objects of substance abstinence.

PMID- 15495809
TI  - [Study of DNA identification in burned bones].
AB  - OBJECTIVE: For the purpose of solving a problems of DNA testing of burned bones.
      METHODS: We present a novel strategy to obtain DNA from burned bones based on the
      use of cetyltrimethylammonium bromide (CTAB) lysis buffer and isoamyl alcohol
      chlorophorm extraction with subsequent DNA purification using the DNA IQ System.
      RESULTS: The methods were found to be effective in removing the PCR inhibitors
      from the burned bone. Then the extracted DNA was successfully genotyped by using
      the florescence labeling STR multiplex method. CONCLUSION: The results of this
      research will assist forensic scientists in the identification of DNA from
      victims whose bodies underwent significant trauma or burning, precluding the
      utilization of traditional forensic DNA identification techniques.

PMID- 15495810
TI  - [A study of genetic polymorphism of the STR locus D7S2846, D19S400 and D18S535 in
      Han population in Wenzhou].
AB  - OBJECTIVE: To study genetic polymorphism of D7S2846, D19S400 and D18S535 in Han
      population in Wenzhou. METHODS: DNA was extracted with chelex-100 method from
      EDTA-blood samples of 194 unrelated individuals in Wenzhou and amplified with PCR
      technique. The PCR products were analyzed by PAG vertical electrophoresis and
      silver-stain. RESULTS: 6 alleles and 15 genotypes of D7S2846, 10 alleles and 36
      genotypes of D19S400, 8 alleles and 26 genotypes of D18S535 was observed. The
      heterozygosities of the three loci are 0.644, 0.724 and 0.772; The power of
      discriminating are 0.854, 0.940 and 0.938. CONCLUSION: The heterozygosities of
      the three loci are high and the frequencies was in accordance with Hardy-Weinberg
      equilibrium (P>0.05), so the three loci can be used in forensic medicine and in
      other genetic researches.

PMID- 15495811
TI  - [A genetic study of 15 STR loci in Chinese E Wen-ke population].
AB  - OBJECTIVE: To investigate the genetic polymorphisms of 15 STRs loci in Chinese E
      Wen-ke population. METHODS: DNA samples from 99 unrelated individuals in Chinese
      E Wen-ke population were screened by Power Plex 16 System and ABI3100 Genetic
      Analyzer. RESULTS: The genotype frequencies of these 15 STR loci meet the Hardy
      Weinberg expectation. The Matching probability of 15 STRs loci were between
      0.0205-0.1733, discriminating power (DP) at 0.8267-0.9795, heterozygosity (Ho) at
      0.6061-0.9091, power of exclusion (PE) at 0.4038-0.7690, polymorphism information
      content (PIC) at 0.5985-0.8734. The total DP of 15 STRs loci is 0.9999999999998.
      CONCLUSION: Our results showed that the 15 STRs loci of Power Plex 16 System are
      valuable STR loci genetic marker system having high DP and are useful in forensic
      case work in Chinese E Wen-ke population.

PMID- 15495812
TI  - [A genetic study of 15 STR loci in Chinese East Mongolian population].
AB  - OBJECTIVE: To investigate the genetic polymorphisms of 15 STRs loci in Chinese
      East Mongolian population. METHODS: DNA samples from 105 unrelated individuals in
      Chinese East Mongolian population were screened by Power Plex 16 System and
      ABI3100 Genetic Analyzer. RESULTS: The genotype frequencies of these 15 STR loci
      meet the Hardy-Weinberg expectation. The Matching probability of 15 STRs loci
      were between 0.0084-0.2169, discriminating power (DP) at 0.7831-0.9916,
      heterozygosity (H) at 0.5619-0.9231, power of exclusion (PE) at 0.4490-0.8444,
      polymorphism information content (PIC) at 0.5438-0.9178. The total DP of 15 STRs
      loci is 0.9999999999998. CONCLUSION: Our results showed that the 15 STRs loci of
      Power Plex 16 System are valuable STR loci genetic marker system having high DP
      and are useful in forensic case work in Chinese East Mongolian population.

PMID- 15495813
TI  - [Progression of the manner of cardiomyocyte death and its potential significance
      in forensic medicine].
AB  - The manner of cell death is a hotspot of medical researchers. Apoptosis and
      necrosis were considered as two manners of cell death in the past. But recently a
      new manner of cell death--oncosis is gradually accepted by the pathologists.
      Oncosis is different from apoptosis in morphologic, mechanism and the role in
      cardiovascular diseases. In this paper, the progression of the research about
      manner of the cardiomyocyte death and its significance in forensic medicine in
      recent years was reviewed.

PMID- 15495814
TI  - [Mitochondrial apoptotic signaling pathway in neurons following brain injury
      induced by hypoxia].
AB  - Impairment of neuronal mitochondria following hypoxia of brain not only result in
      nerve cell's energy-deprivation and dysfunction, mitochondria also play key roles
      in apoptosis of neurons. A central step being the release of cytochrome c (cyt c)
      across the outer mitochondrial membrane into the cytoplasm through opening of the
      mitochondrial permeability transition pore. Releasing of cytochrome c induce to
      downstream consequences of specific caspase activation. The antiapoptotic and
      proapoptotic members of the Bcl-2 family regulate mitochondrial activities
      relevant to apoptotic signaling by influencing the realaseing of cyt c.

PMID- 15495815
TI  - [Study of toxicology of strychnos].
AB  - Because of its officinal value, strychnos is widely used by clinic and
      individual. Since toxic dose and therapeutic dose are very close, strychnos
      poisoning cases are frequently reported. In this paper the chemical component,
      toxic dose, mechanisms of toxicity, poisoning symptom and pathological changes
      after strychnos poisoning are reviewed.

PMID- 15495816
TI  - [The study developments about changes of methamphetamine-induced genes'
      transcriptions and translations].
AB  - The basic changes are to transform the levels of many genes' transcriptions and
      translations when methamphetamine is injected into the organism. Those genes
      enclose four classes: genes intermediating the damages or death of neurons,genes
      involving circadian rhythms of activity, genes concerning the abnormality of
      behaviors and some genes difficult to be classified. The transformations of the
      transcriptions or translations of these genes cooperate to produce many clinic
      syndromes of methamphetamine-addictors. Moreover, the study of these genes can
      provide testimonies to forensic identification.

PMID- 15495817
TI  - [Present status of peripheral angiopathy treated by integrative Chinese and
      Western medicine].

PMID- 15495818
TI  - [Study on relationship between the polymorphism of angiotensin converting enzyme
      gene and blood stasis syndrome in patients with coronary heart disease].
AB  - OBJECTIVE: To explore the relationship between the insertion/deletion (I/D)
      polymorphism of angiotensin converting enzyme (ACE), and blood stasis syndrome
      (BSS) in patients with coronary heart disease (CHD). METHODS: The ACE gene type
      in 48 patients of CHD of BSS type, 52 CHD patients of non-BSS type and 54 healthy
      subjects (control) was determined by PCR assay, also levels of endothelin (ET),
      angiotensin II (Ag II), and nitric oxide (NO) were determined. RESULTS:
      Occurrence of DD genotype and allele genotype of ACE gene was higher in patients
      of BSS than that in patients of non-BSS and control (P < 0.01). ET/NO level was
      higher in patients of BSS than that in control (P < 0.01). ET and Ag II levels in
      patients of BSS were significantly higher than those in patients of non-BSS (P <
      0.05) and control (P < 0.01). Levels of ET/NO and Ag II in subjects with DD
      genotype in various groups were higher than those in subjects with Ag II or ID
      genotype, the highest level occurred in patients of BSS with DD genotype, when
      compared with the other two groups, the difference in Ag II was significant (P <
      0.05 and P < 0.01), when compared with control, the difference in ET/NO was
      significant (P < 0.01). CONCLUSION: DD genotype of ACE gene may be the
      susceptible gene of CHD in patients of BSS type.

PMID- 15495819
TI  - [Constructing a Cox proportional hazard regression model of prognosis factors of
      acute myocardial infarction by retrospective cohort study].
AB  - OBJECTIVE: To study the effects of the potential factors, including Chinese
      herbal decoction, on the long-term prognosis of acute myocardial infarction
      (AMI). METHODS: Previous clinical data of 162 patients with AMI were collected,
      who were followed-up to observe the important events for prognosis, as death and
      cardio-cerebral episode, and the Cox proportional hazards regression model was
      used to assess the relative factors. RESULTS: The degree of cardiac function (by
      New York grading) increased 1 grade when age increased for 10 years, and the
      relative hazardous degree (RHD) raised to 1.983 and 3.169. After treatment with
      Chinese herbal decoction and angiotensin converting enzyme inhibitor (ACEI), the
      RHD could be reduced to 0.177 and 0.161 respectively. Taking the important cardio
      cerebral events, including death, as the endpoint, when age increased for 10
      years, the cardiac function would increase for 1 grade and RHD of endpoint events
      increased to 2.021 and 1.863, if patients had history of anterior infarction,
      arrhythmia and diabetes mellitus, it increased to 2.903, 2.588 and 4.039
      respectively. Chinese decoction and ACEI treatment could reduce it to 0.093 and
      0.141 respectively. CONCLUSION: Age, heart failure, anterior infarction,
      arrhythmia and diabetes mellitus are the hazardous factors of the long-term
      prognosis of AMI, Chinese herbal decoction and ACEI are the protective factors.

PMID- 15495820
TI  - [Effect of oral administration of guanxin II decoction on coronary blood flow and
      cardiac systolic/diastolic function in healthy males].
AB  - OBJECTIVE: To observe the effects of oral administration of guanxin II decoction
      (GX II) on cardiovascular function, especially on the dynamics of coronary blood
      flow in healthy males. METHODS: Changes of heart rate, diastolic pressure,
      systolic pressure, left ventricular ejection fraction (LVEF), E peak, A peak, E/A
      value of mitral flow, diastolic peak velocity (Vmax) and diastolic flow velocity
      time integrals (VTI) of left anterior descending coronary artery (LAD) in 11
      healthy male subjects were measured before and after oral administration of GX
      II, using non-invasive echocardiogram. RESULTS: Compared with those before GX II
      administration, the changes after administration in heart rate, systolic
      pressure, diastolic pressure, LVEF, E peak, A peak and E/A value, were
      insignificantly different (P>0.05), but the Vmax and VTI significantly increased
      at 30 min, 60 min, 90 min and 120 min after GX II administration (P<0.05).
      CONCLUSION: To increase the coronary blood flow is possibly one of the mechanisms
      of GX II in treating coronary heart disease and angina pectoris.

PMID- 15495821
TI  - [Study on the effect and mechanism of puerarin on the size of infarction in
      patients with acute myocardial infarction].
AB  - OBJECTIVE: To observe the effect of puerarin on infarction size, fatty acids
      metabolism, inflammatory response and atherosclerotic plaque stability in
      patients with acute myocardial infarction (AMI). METHODS: Sixty-one patients with
      AMI were randomly divided into two groups, the control group (n = 30) and the
      treated group (n = 31). All were treated with conventional treatment, but to the
      treated group, puerarin injection was given additionally by injecting 500 mg per
      day for 2 weeks. Before and after treatment, blood levels of free fatty acids
      (FFA), matrix metalloproteinases-9 (MMP-9) and C-reactive protein (CRP) were
      assayed, and the size of infarction was determined by Ideker QRS scoring method.
      RESULTS: Before treatment, the size of infarction was positively correlated to
      the levels of FFA, MMP-9 and CRP (r = 0.43, 0.42 and 0.39, respectively, all
      P<0.01). As compared with those before treatment, after treatment, the three
      parameters lowered by 30%, 41% and 23%, respectively and the size of infarction
      significantly reduced in the treated group (P<0.01), while in the control group,
      no significant change was found (P>0.05). CONCLUSION: Puerarin treatment could
      significantly reduce the size of infarction in patients with AMI, the mechanism
      is possibly related with its effects in lowering plasma levels of FFA, inhibiting
      inflammation and stabilizing atherosclerotic plaque.

PMID- 15495822
TI  - [Clinical study on manifestation of hepatolenticular degeneration complicated
      with epilepsy and therapeutic effect of integrative Chinese and Western medicine
      treatment].
AB  - OBJECTIVE: To observe the clinical manifestation of 155 patients with
      hepatolenticular degeneration (HLD) complicated with epilepsy and the therapeutic
      effect of integrative Chinese and Western medicine treatment on them. METHODS:
      Clinical manifestation of patients and its relationship with abnormalities in
      cranial CT and/or MRI were observed. Patients were treated by combined treatment
      of copper repellent with sodium dimercaptosulfonate 20 mg/kg per day by
      intravenous dripping, and modified Gandou Decoction (GDD) by oral intake and
      antiepileptics as well, after treatment for 8-10 courses, the clinical effect,
      copper levels in urine and serum were compared between groups. RESULTS: In the
      155 HLD patients, 96 were complicated with petit mal and 59 with grand mal. In
      the CT and/or MRI conducted in 72 patients, all showed abnormal images, besides
      such frequently met images as bilateral symmetrical basal ganglia focal lesion in
      65 case-episode (90.3%) and brain atrophy of various degrees in 61 case-episode
      (84.7%), the massive lesions in cerebral white matter as principal, with the
      cortex involved, were also found in 54 patients (74%), which were mostly
      bilateral and symmetric or located in 2 adjecent lobes of brain, the sites of
      damage, in sequence of occurrence, were frontal lobe, parietal lobe, temporal
      lobe and callosal gyrus. Brain atrophy was found in all the remained patients
      without above-mentioned lesions. Abnormal EEG was shown in 29 patients (40.2%),
      which mainly manifested as theta wave of moderate to high potential and/or short
      paroxysmal spike-slow or sharp-slow complex wave evoked. The urinary copper level
      in patients after treatment was 34.5 +/- 21.6 micromol/24 hrs, significantly
      higher than that before treatment, 4.49 +/- 1.93 micromol/24 hrs (P < 0.01). And
      the serum copper level in patients also lowered significantly (P< 0.01).
      Epileptic seizure was controlled completely along with the gradually improving of
      extrapyramidal symptoms. CONCLUSION: Partial seizure was the most common type of
      seizure of HLD patient complicated with epilepsy, the next is systemic seizure.
      Cerebral damage lesion and obvious brain atrophy could be the main etiological
      factors of HLD complicated with epilepsy, combined copper repellent therapy of
      integrative Chinese and Western medicine, and antiepileptics produced good
      clinical effect on the patients.

PMID- 15495823
TI  - [Characteristic changes of vascular tension factors in diabetic arterial
      occlusion of lower extremities].
AB  - OBJECTIVE: To study the change of vascular tension factors (VTF), including
      vascular contractile factors as endothelin-1 (ET-1), thromboxane A2 (TXA2) and
      vascular dilatory factors as nitric oxide (NO), prostacyclin (PGI2), in different
      stage of peripheral diabetic arterial occlusion (PDAO), and to preliminarily
      explore the clinical significance of these changes. METHODS: VTF in 40 diabetic
      patients, 15 of 2nd stage and 25 of 3rd stage, were observed by measuring level
      of ET-1, NO, TXB2 and 6-keto-PGF1alpha in blood plasma with RIA assay. RESULTS:
      (1) ET-1 and TXB2 levels in all patients were higher than those in control (P <
      0.05 and P < 0.01), those in patients of 3rd stage was higher than those of 2nd
      stage, showing significant difference (P < 0.05). (2) NO and 6-keto-PGF1alpha
      levels in all patients was lower than those in control, but showed no significant
      difference between patients of various stages (P > 0.05). CONCLUSION: There are
      changes of VTF in patients with PDAO, manifesting as increase of vascular
      contractive factors and decrease of vascular dilative factor. The changes are
      diffrent in various stages, the vascular contractive and thrombotic factors in
      patients of 3rd stage are higher than those in patients of 2nd stage, but the
      injury on vascular dilative factors in the two stages showed insignificant
      difference.

PMID- 15495824
TI  - [A 16-year clinical observation on 217 chronic HBsAg carriers].
AB  - OBJECTIVE: By means of observing the clinical development of asymptomatic chronic
      HBsAg carriers (AsC) to explore the clinical rule of development of chronic
      hepatitis B (CHB) to liver cirrhosis (LC) to hepatocellular carcinoma (HCC) and
      to seek effective method for blocking the procedure. METHODS: AsCs were selected
      from health examination according to the diagnostic standard from the National
      Program for Prevention and Treatment of Viral Hepatitis, by periodical or non
      periodical conventional examination of liver diseases, mixed infection of HCV was
      excluded. A 16-year systematic observation on clinical process of HBV infection
      series was completed. RESULTS: In the 217 AsCs observed, 21 cases (9.68%) with
      the HBsAg negatively converted, the average year negative conversion rate being
      0.58%, among them, 13/21 cases (61.9%) had production of anti-HBs antigen; 20
      cases were clinically cured; 1 case transferred to HCC; 124 cases (57.14%)
      remained asymptomatic carriers; 73 transferred to chronic liver disease, showing
      a tendency of gradually developing from CHB to LC to HCC, the year transferring
      rate from AsC to LC and HCC being 1.04% and 0.40%, respectively. Fifteen patients
      died of liver diseases, in which one died of severe CHB, 3 of LC and 11 of HCC.
      CONCLUSION: Different clinical end-results may reveal in AsCs according to their
      age and regulation on immune response to HBV. Few of the HCC and LC patients were
      HBeAg (e+) positive, they often reveal HBeAg (e-) negative or anti-HBe positive.
      HCC always develops on the basis of liver fibrosis or cirrhosis, which are the
      prophase of HCC, and patients with liver fibrosis or cirrhosis are the high risk
      group of developing HCC. HCC is not only the terminal pathologic stage of
      hepatopathy, but also one of the most important factors that causes death of
      chronic hepatopathy. From the viewpoint of integrative medicine in typing
      hepatopathy to observe the clinical speciality of AsC developing to CHB, LC and
      HCC, it is considered that the degree of blood stasis is in accordance with the
      development of hepatopathy.

PMID- 15495825
TI  - [Relationship of plasma endotoxin level with TCM deficiency/excess syndrome and
      grading/staging of pathologic change of liver in patients with chronic
      hepatitis].
AB  - OBJECTIVE: To explore the relationship of plasma endotoxin level with TCM
      deficiency/excess Syndrome and the grading/staging of pathologic change of liver
      in patients with chronic hepatitis B (CHB). METHODS: Plasma level of endotoxin
      (ET) was determined using chromogenic limulus amebocyte lysate (LAL) assay in 75
      patients with chronic hepatitis B (30 of excess dominance, 45 of deficiency
      dominance) and also in 15 healthy subjects for control. Moreover, pathological
      examination on liver biopsy of 20 patients was conducted. RESULTS: (1) ET level
      increased in all CHB patients, and the increment was higher in patients of excess
      dominance than that in patients of deficiency dominance, showing significant
      difference (P < 0.01). (2) Correlation between ET level and liver pathological
      grading/staging was shown in CHB patients. CONCLUSION: Plasma level of ET could
      be taken as one of the criteria of TCM microcosmic diagnosis in differentiating
      deficiency/excess syndrome. (2) Endotoxemia plays an important role in pathologic
      process of liver injury.

PMID- 15495826
TI  - [Clinical study on application of bailing capsule after renal transplantation].
AB  - OBJECTIVE: To observe and assess the immunosuppressive effect of applying bailing
      capsule (BLC, a dry powder preparation of Cordyceps sinensis mycelia), after
      renal transplantation, its influence on other systems of organism, and to explore
      the possible therapeutic mechanism. METHODS: One hundred and twenty-one
      recipients of renal homo-allograft were randomly divided into two groups. The 64
      cases in Group A was treated with cyclosporin A (Cs A) + prednisone (pred) +
      azathioprine (Aza), the 57 in Group B treated with Cs A + pred + BLC. They were
      followed-up for 1-2 year by checking up blood routine, urine routine, liver and
      renal function, blood electrolytes, glucose and lipids, and uric acid for 2 times
      every week in the first month after transplantation, followed by proper re
      examination of these items according to various condition. RESULTS: There was no
      significant difference between the two groups in aspects of graft survival rate,
      occurrence of reject reaction, renal function recovery, blood electrolytes and
      blood glucose levels. However, as compared with Group A, in Group B, levels of
      urinary erythrocytes and leucocytes, blood alanine transaminase (ALT), aspartate
      aminotransferase (AST), total cholesterol, uric acid as well as the incidence of
      infection were significantly lower, and blood high density lipoprotein, serum
      total protein, albumin, RBC and WBC count were significantly higher. CONCLUSION:
      BLC could effectively prevent the reject response after renal transplantation,
      protect renal and liver function, stimulate hemopoietic function, improve
      hypoproteinemia and hyperlipidemia, reduce the infection, etc., therefore, it is
      an ideal immunosuppressor after organ transplantation.

PMID- 15495827
TI  - [Antagonistic effect of yishen ruanjian san contained serum against aristolochic
      acid in antagonizing human renal interstitial fibroblasts].
AB  - OBJECTIVE: To study whether yishen ruanjian san contained serum (S-YRS) could
      intervene the action of aristolochic acid (AA) in antagonizing human renal
      interstitial fibroblasts (hRIFs) to induce extracellular matrix (ECM)
      accumulation. METHODS: AA-Na 40 microg/ml, with or without 10% S-YRS, was co
      cultured with hRIFs, then the hRIFs mRNA of transforming growth factor-beta1 (TGF
      beta1), connective tissue growth factor (CTGF), plasminogen activator inhibitor-1
      (PAI-1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and type I collagen
      (Col I) in the cultured cells were detected by RT-PCR, and their protein
      expression monitored with ELISA and Western blot respectively. RESULTS: The mRNA
      and protein expression of all the above-mentioned factors were significantly up
      regulated by AA-Na (P < 0.05). Excepting PAI-1, the enhanced mRNA and protein
      expression were significantly down-regulated by S-YRS (P < 0.05). CONCLUSION: S
      YRS could down-regulate the hRIF to promote the expression of ECM synthesis
      factors and inhibit the ECM degradation factors in hRIFs, so as to antagonize the
      AA stimulated accumulation of ECM such as Col I.

PMID- 15495828
TI  - [Effect of jiantai liquid on expression of estrogen and progesterone receptors in
      uterus of mice with embryo implantation dysfunction induced by mifepristone].
AB  - OBJECTIVE: To explore the molecular mechanism of jiantai liquid (JTL) in
      improving endometrial receptivity of mice with embryo implantation dysfunction
      (EID). METHODS: Mice model of EID induced by mifepristone were intervened with
      JTL (Twig of Chinese Taxillus, Red Sage root, Chinese Angelica, Milkvetch root,
      Chuanxiong rhizome), and sacrificed on day 8 of pregnancy. The endometrial
      estrogen receptor (ER) and progesterone receptor (PR) protein and their gene
      expressions were assessed by Western blot and semi-quantitative reverse
      transcriptase polymerase chain reaction (RT-PCR). RESULTS: Levels of ER and PR
      protein and their gene expressions in the JTL treated group were significantly
      higher than those in the model group respectively (all P < 0.05), and showed
      insignificant difference from those in the normal control group (all P > 0.05).
      CONCLUSION: JTL could promote the development of endometrium and improve the
      embryo implantation by way of regulating the levels of ER and PR protein and gene
      expression in mice with EID.

PMID- 15495829
TI  - [Study on effect of berbamine on multidrug resistance leukemia K562/Adr cells].
AB  - OBJECTIVE: To study the effect and mechanism of berbamine on the apoptosis of
      multidrug resistant leukemia K562/Adr cells and in reversing the drug resistance.
      METHODS: IC50 value of K562/Adr cell was determined with MTT method, cell
      apoptosis rate was analyzed by flow cytometry with Annexin V FITC-PI assay, with
      the peak and cell cycle detected by PI staining. At the same time, flow cytometry
      was also used in determining Caspase-3, P-GP protein expression and drug
      accumulating capacity in cells, and RT-PCR method was used to analyze the gene
      expression of mdr-1. RESULTS: Berbamine could inhibit human leukemia K562/Adr
      cell growth in dose-dependent manner, it could also induce cell apoptosis,
      increase the protein expression of Caspase-3 and the drug excretion capacity of
      cells, reduce the mRNA and protein expression levels of mdr-1 gene. CONCLUSION:
      Berbamine could activate Caspase-3 to induce human leukemia K562/Adr cell
      apoptosis, and by reducing mdr-1 gene expression to reverse its multidrug
      resistance.

PMID- 15495830
TI  - [Effect of jianxin pinglu pill on arrhythmia and aquaporin 4 expression in rats
      with myocardial ischemia/reperfusion injury].
AB  - OBJECTIVE: To explore the effect of jianxin pinglu pill (JPP) on arrhythmia and
      aquaporin 4 (AQP4) in rats with myocardial ischemia/reperfusion (I/R) injury.
      METHODS: The effects of JPP on arrhythmia, mortality and AQP4 on I/R injured rats
      model induced by blocking left coronary artery were observed using II lead of
      ECG, HE stain and AQP4 immunohistochemical stain. RESULTS: JPP showed significant
      effect in lowering the arrhythmia occurrence and mortality, reducing myocardial
      ischemic edema and injury, strengthening AQP4 expression in myocardial tissue.
      CONCLUSION: JPP has the effect of preventing I/R induced arrhythmia, it might be
      related with its action in up-regulating AQP4 expression level in myocardium and
      reducing the intracellular edema.

PMID- 15495831
TI  - [Effect of extract from Tripterygium hypoglaucum on proliferation and apoptosis
      of vascular smooth muscle cells].
AB  - OBJECTIVE: To study the effect of THW-4, an extract from Trypterygium hypoglaucum
      on proliferation and apoptosis of vascular smooth muscle cells (VSMC). METHODS:
      VSMC derived from rabbit aorta were cultured in vitro and different
      concentrations of THW-4 were added in experimental groups. Cell proliferation was
      evaluated by MTT and apoptosis by transmission electron microscopy (TEM), TUNEL
      assay and Annexin V-FITC/PI double labelled assay. RESULTS: The inhibitory
      effects of THW-4 on proliferation of VSMC displayed dose-time dependently, with
      the IC50 value of 15.6 microg/L at 48 hrs. Incubated with THW-4 (10-100 microg/L)
      for 56 hrs, VSMC mainly appeared early stage apoptosis and the percentage of
      apoptosis was found to raise along with the increase of the THW-4 concentration.
      Typical images of apoptosis could be observed under TEM and TUNEL assay showed
      increase of DNA segments with karyorrhexis and pyknosis after THW-4 treatment for
      72 hrs. Analysis of cell cycle indicated the THW-4 mainly lead to the blockage of
      VSMC in G2/M stage. CONCLUSION: THW-4 could inhibit the proliferation and induce
      the apoptosis of VSMC in vitro, suggesting that THW-4 is a potential agent for
      prevention of restenosis following angioplasty.

PMID- 15495832
TI  - [Effect of mailuoning on C-Fos protein expression in rats with cerebral
      infarction].
AB  - OBJECTIVE: To investigate the protective effect of mailuoning (MLN) on nerve
      cells after cerebral infarction induced by photochemistry. METHODS: Eighty SD
      rats were divided into three groups, the control group (n = 20), the model group
      (n = 30) and the MLN group (n = 30). Focal cerebro-ischemia induced by
      photothrombosis in adult rat was used as a model. Changes of C-Fos protein
      expression before and after MLN treatment were observed using
      immunohistochemistry, computerized imaging technique and transmission electron
      microscopy (TEM). RESULTS: C-Fos positive cells located in the transitional zone
      between the necrotic core and normal cortex. C-Fos protein expression began to
      show 3 hrs after cerebral infarction, peaked at 6 hrs. As compared with the model
      group, C-Fos expression was significantly reduced in the MLN group (P<0.01).
      CONCLUSION: MLN could markedly reduce the injury of nerve cell in the
      transitional zone, the protection may be related with its inhibition on C-Fos
      protein expression.

PMID- 15495833
TI  - [A prospective controlled study on the clinical therapeutic effect of treatment
      of menstrual syndrome by isoflavone of soybean].

PMID- 15495834
TI  - [Clinical observation on effect of dishengzhu decoction in treating vascular
      dementia].

PMID- 15495835
TI  - [Clinical observation on the treatment of middle-late stage liver carcinoma by
      combined therapy of hepato-arterial chemo-embolising and Chinese drugs for
      strengthening pi and regulating qi].

PMID- 15495836
TI  - [Study on the regulation of HPAT axis molecular network in patients with aging
      physiologic shen-deficiency syndrome].

PMID- 15495837
TI  - [Proteome and study on the essential of TCM syndromes].

PMID- 15495838
TI  - [Regulating antigen presentation--anti-tumor immuno-therapy by integrative
      Chinese and Western medicine].

PMID- 15495839
TI  - [Analysis on 638 cases of adverse reaction induced by Chinese patent drugs].

PMID- 15495840
TI  - [Influences of combined use of Chinese and Western drugs on cytochrome P450
      enzyme system].

PMID- 15495841
TI  - Young children's difficulty with adjectives modifying nouns.
AB  - In two experiments we tested the hypothesis that children have a basic problem in
      mastering the attributive relation because it involves a two-step logical
      semantic integration process of the head-noun and the attributive adjective.
      Hebrew-speaking children were asked to interpret highly familiar adjective-noun
      combinations by selecting a photo that depicted the correct referent. In
      Experiment I there were four choices for each adjective-noun pair: correct
      object/correct property, correct object/wrong property, wrong object/correct
      property, wrong object/ wrong property. 170 children (1.6-4.4) participated.
      Analyses of errors and spontaneous self-corrections indicated that children
      initially ignored the adjective and based their responses only on the noun. In
      Experiment 2, in addition to the 4-choice condition, there were two simpler
      conditions with only two choices: the correct object/correct property, and either
      the correct object/wrong property, or the wrong object/correct property. 30
      children (1.9-4.11) were tested. The children, and in particular the lowest
      scoring third of the sample, did significantly better in the 2-pictures
      conditions. The results suggest that young children do possess a basic adjective
      vocabulary and can use it in simple discriminations, but have a considerable
      difficulty in integrating the information furnished by the adjective with
      information furnished by the noun.

PMID- 15495842
TI  - A longitudinal study of language development in two children with Williams
      syndrome.
AB  - Williams syndrome (WS) is often cited as the prime example within developmental
      disorders of the dissociation of language from other cognitive skills,
      particularly from visuo-motor skills. This claim has been responsible for the
      challenges posed by this population to cognitive theories and to models of
      language acquisition. Two Hebrew-speaking children with WS were followed
      longitudinally for 18 months, from the first occurrences of two word
      combinations. Y was 3.9-5.3 and BT was 4.2-5.8 during data collection. Both
      children had an MLU of 1.8-2.8. The children's linguistic profiles were compared
      to the profiles of typically-developing (TD) children of similar MLU as well as
      to the profiles of 11 children with a variety of neurodevelopmental disorders
      (ND), matched on MLU. The profiles exhibited by the children with WS throughout
      the period of the study differed from the profiles seen in both control groups.

PMID- 15495843
TI  - Genetic and environmental interactions in determining the early lexicon: evidence
      from a set of tri-zygotic quadruplets.
AB  - A set of tri-zygotic quadruplets, three girls and one boy, participated in weekly
      observations from 1.2 to 1.10 (years;months), a period of transition from
      prelinguistic gesture to 50 words. In the study, one girl served as a genetic
      mate to her identical twin and a biological risk mate to her fraternal sister.
      The biological risk mates achieved milestones in lexical development at similar
      times; however, the genetic mates demonstrated more similarities in pattern of
      lexical development and in the modality of their word productions. Degree of
      similarity changed over the observation period. Imposed upon the natural
      experiment was a within-subject manipulation of the social environment: The
      experimenters modelled a core vocabulary via the gesture + verbal modalities to
      the children during each visit. The modelling resulted in increased rates of word
      learning for three of the children; the child with the greatest biological risk,
      the boy, derived the greatest benefit. The findings provide unique support for a
      dynamic, multi-factorial model of lexical development involving the interaction
      of genetics, the biological environment and the social environment. Furthermore,
      they illustrate the robustness of early lexical development in the face of
      biological risks.

PMID- 15495844
TI  - Linguistic indicators of inter-genre differentiation in later language
      development.
AB  - The paper examines two types of texts, personal experience narratives and
      expository discussions, dealing with the shared theme of interpersonal conflict.
      Both were produced by the same 80 subjects, participants in a crosslinguistic
      study on developing literacy: gradeschoolers aged 9.0 to 10.0, twelve-to-thirteen
      year-old junior high school students, sixteen-to-seventeen-year-old high school
      students, and graduate-level university students. The study reported here aims to
      demonstrate that inter-genre differentiation is evident from an early age and is
      reflected by distinct forms of expression across different interlocking
      linguistic systems. In keeping with the focus on relations between linguistic
      forms and discourse functions that motivates our study, we further aim to show
      how particular grammatical elements can fulfil different discourse functions
      across development. To this end, we analysed several different lexical and
      morphosyntactic constructions in 160 Hebrew-language texts as diagnostic of inter
      genre distinctiveness: subjectless constructions; verbless copular clauses; verb
      types and the temporal categories of verb tense and mood, including lexical
      expressions of modality in the two genres. Results show that narratives are
      clearly distinguished from expository texts along all these dimensions; these
      distinctions are evident from the youngest age group we considered; and with age,
      inter-genre differentiation emerges as more moderately dichotomous. We concluded
      from this that maturely proficient text construction is able to combine
      expository-type generalizations with narrative event-description and to
      intersperse narrative-type illustrative episodes with expository formulation of
      ideas.

PMID- 15495845
TI  - The acquisition of word connotations: asking 'what happened?'.
AB  - Although words have both denotative and connotative meanings, there has been
      little research on the child's acquisition of connotations. In large segments of
      written texts, connotations can be studied by examining word co-occurrences
      (collocations). Using this technique, corpus linguists have found, for example,
      that 'happen' has a negative connotation; it most often collocates with negative
      words (e.g. 'accidents', 'something dreadful'). The current research is a case
      study of the use of the lemma 'happen'. Adult production of
      'happen/happens/happening/happened' was examined in 151 American English
      speaking, adult-child dyads from the CHILDES database. Within these dyads, 35
      children used 'happen' and its variants. Both adults and children were
      increasingly likely to use 'happen' to describe negative contexts as children's
      language progressed from MLUs around 1.00 to MLUs greater than 4.00. Results are
      consistent with usage-based theories of language that claim that the relative
      frequency of information in the input is critical to language learning.

PMID- 15495846
TI  - On the use of the connective 'and' in oral narration: a study of French-speaking
      elementary school children.
AB  - The study deals with children's use of the connective and to end a story. One
      hundred and ninety-one children (aged 7.0 to 11.0) who were native speakers of
      French told two-character comic strip stories with no text to a same-age peer. In
      the consecutive-display condition, the comic strip was in booklet format with one
      frame per page, whereas in the simultaneous-display condition, all frames were on
      the same page. In the arbitrary-sequence condition, the events in each comic
      strip, although presented as a sequence, could have occurred in any order,
      whereas in the ordered-sequence condition, the order of the events could not be
      changed. In the maintained-topic condition, the materials were designed to induce
      a thematic subject right after the first frame (by the repeated presence of the
      same character in every picture, up to and including the last one), whereas in
      the changed-topic condition, the other character appeared alone in the last
      frame. The analysis focused on cases where the children began the narration of
      the last frame using and to change the text pattern established so far. The
      results showed that and was often used in this way (35.2% of the productions),
      especially in the experimental conditions that facilitated event interconnection
      (simultaneous display, ordered sequence, maintained topic). The ordered-sequence
      condition showed that the nine-year-olds in simultaneous display employed and in
      co-occurrence with another connective, whereas the eleven-year-olds mainly used
      and more specifically: when the topic changed. The discussion deals with the
      specialization during development of the use of and within a speaker's discourse.

PMID- 15495848
TI  - Health care initiatives in Estonia.

PMID- 15495847
TI  - The time for action is now!

PMID- 15495849
TI  - Kudos to Dr. Littman.

PMID- 15495850
TI  - The many faces of public health crises.

PMID- 15495851
TI  - Obesity: the shifting paradigm.

PMID- 15495852
TI  - Childhood obesity: a review of causes, prevention, and the role of the primary
      care provider.

PMID- 15495853
TI  - Bariatric surgery in morbidly obese adolescents.

PMID- 15495854
TI  - Defining overweight in children using growth charts.
AB  - Although the increase in pediatric overweight has paralleled the increase in
      obesity among adults, the definitions of obesity in adults and overweight in
      children are not the same. Empirically determined fixed cutoffs that identify
      increased risk are used for adults while statistical definitions based on
      reference populations are used for children. A variety of reference-data sets for
      BMI in childhood exist. In the United States, the 2000 Centers for Disease
      Control and Prevention (CDC) BMI-for-age growth charts are recommended for
      screening of overweight and at-risk for overweight in childhood. For children and
      teens ages two to 19 years, overweight is defined as a BMI-for-age > or = 95th
      percentile and atrisk for overweight is defined as a BMI-for-age between the 85th
      and 95th percentiles. The 2000 CDC growth charts provide a growth reference, not
      a prescriptive standard, for U.S. children.

PMID- 15495855
TI  - Obesity: a crisis in Maryland.

PMID- 15495856
TI  - Children, the feeding relationship, and weight.

PMID- 15495857
TI  - Taking obesity head on!

PMID- 15495858
TI  - Maryland Health Care Commission electronic medical records--a growing alternative
      to paper charts.

PMID- 15495859
TI  - Talking about dying: ethical obligations and Maryland state law.

PMID- 15495860
TI  - A most difficult challenge.

PMID- 15495861
TI  - Lexicon of war.

PMID- 15495862
TI  - America's biggest threat?

PMID- 15495863
TI  - The tug of the country.

PMID- 15495864
TI  - Talk is valuable: program promotes communication among rural providers.

PMID- 15495865
TI  - OB upgrade: rural hospitals combine resources to train staff.

PMID- 15495866
TI  - Mending broken hearts: can use of angioplasty in community hospitals save lives?

PMID- 15495867
TI  - 911 for rural pediatricians: outstate physicians tap expertise at Children's.

PMID- 15495868
TI  - Primum, non nocere, then what?

PMID- 15495869
TI  - A little fork in the road.

PMID- 15495870
TI  - Long distance service.

PMID- 15495871
TI  - The changing face of rural medicine.

PMID- 15495872
TI  - Starting small.

PMID- 15495873
TI  - An introduction to rural primary care medicine.

PMID- 15495874
TI  - The rural summer internship.

PMID- 15495875
TI  - The Rural Physician Associate Program.

PMID- 15495876
TI  - Minnesota physician workforce analysis: rural supply and demand.
AB  - Considering the physician supply in 2002, the potential number of new physicians,
      and the number of vacancies that year, rural Minnesota has shortages in the
      following specialties: family practice, internal medicine, obstetrics/gynecology,
      pediatrics, general surgery, gastroenterology, ophthalmology, orthopedic surgery,
      otolaryngology, psychiatry, and urology. Metropolitan areas have fewer shortages;
      however, there is a gap between supply and demand in obstetrics/gynecology,
      gastroenterology, general surgery, otolaryngology, and urology. Future areas of
      concern for all parts of the state include family practice, internal medicine,
      obstetrics/gynecology, pediatrics, cardiology, general surgery, psychiatry,
      ophthalmology, orthopedic surgery, and urology. In Minnesota, with several
      specialties facing a substantial number of retirements in the next 10 years, the
      number of new physicians completing graduate medical education remaining steady
      or declining, and the population growing--especially among people ages 65 to 84,
      the current shortages may increase, and additional specialties may experience a
      gap if the supply is not increased.

PMID- 15495877
TI  - Rural-urban differences in cancer care: results from the Lake Superior Rural
      Cancer Care Project.
AB  - Past studies have shown significant differences between rural and urban cancer
      patients in many measures of cancer care. There is little recent information
      about this disparity, which generally has shown disadvantages in rural
      populations. This study reports the rural and urban differences in cancer care
      using data from the Lake Superior Rural Cancer Care Project. The study used a
      prospective, population-based design that included all incident cases of breast,
      colorectal, lung, and prostate cancers diagnosed in northeastern Minnesota,
      northwestern Wisconsin, and the western portion of Michigan's Upper Peninsula
      from 1992 to 1997. The outcome measures were 9 endpoints that represented state
      of-the-art cancer care during the study. Rural cancer patients as compared with
      their urban counterparts were disadvantaged in proportion staged, stage at
      diagnosis, initial management procedures, post-treatment surveillance testing,
      and participation in cancer clinical trials. These findings are similar to
      previously published studies. Further research is needed to determine more
      clearly the barriers in rural cancer care and to find more effective strategies.

PMID- 15495878
TI  - Participatory research in rural primary care.
AB  - Translating research into practice will require researchers to develop new
      methods and approaches. Standard randomized control trials may help determine the
      efficacy of a test or treatment but are unlikely to help identify what will make
      it possible to implement that new test or treatment in everyday practice. Rural
      practices may have unique needs that are best addressed using a participatory
      research model that allows collaboration among the researchers and those being
      studied. This article gives one example of participatory research used to help
      translate asthma guidelines into primary care in rural Minnesota practices.

PMID- 15495879
TI  - Some doc.

PMID- 15495881
TI  - Comments on "Tuberculosis screening in college students" the devil is in the
      details.

PMID- 15495880
TI  - Tuberculosis prevention in college students.

PMID- 15495882
TI  - A close look at why one social norms campaign did not reduce student drinking.
AB  - The authors examined 3 possible explanations for the failure of a social norms
      campaign at a large public university. They administered an anonymous survey to 2
      random samples of undergraduate classes: a baseline assessment of 616 students
      before the campaign's implementation and a follow-up survey of 723 students 4
      academic years later. At follow-up, 66.5% of the students were aware of the
      campaign, yet the survey revealed no reduction in perceived drinking norms or
      alcohol use in this group. An analysis of the postcampaign sample revealed that
      (1) a majority of the students did not find the statistics used in the campaign
      messages credible, (2) higher levels of alcohol use predicted lower levels of
      perceived campaign credibility, and (3) only 38.5% of the students understood the
      campaign's intended purpose. If they are to influence personally relevant
      drinking norms, these campaigns must undergo further development to enhance
      message credibility and participants' understanding.

PMID- 15495883
TI  - College smoking-cessation using cell phone text messaging.
AB  - Although rates of smoking among college-aged students continue to rise, few
      interventions that focus on college smokers' unique motivations and episodic
      smoking patterns exist. The authors developed and evaluated a prototype program
      targeting college students that integrates Web and cell phone technologies to
      deliver a smoking-cessation intervention. To guide the user through the creation
      and initialization of an individualized quitting program delivered by means of
      cell phone text messaging, the program uses assessment tools delivered with the
      program Web site. Forty-six regular smokers were recruited from local colleges
      and provided access to the program. At 6-week follow-up, 43% had made at least
      one 24-hour attempt to quit, and 22% were quit--based on a 7-day prevalence
      criterion. The findings provide support for using wireless text messages to
      deliver potentially effective smoking-cessation behavioral interventions to
      college students.

PMID- 15495884
TI  - A collaborative approach to nutrition education for college students.
AB  - It is well established in the literature that college students have poor eating
      habits and that many barriers exist to achieving optimal nutrition for this busy
      population. Little is known about students' perceptions of this problem or
      suggestions for improving their dietary habits. Similarly, college health
      professionals need innovative approaches to nutritional education. In an effort
      to develop an online nutrition resource specifically geared to college students,
      the authors assessed the availability of Internet-based nutritional information
      for this population and conducted focus groups with students and health
      professionals to identify relevant nutrition concerns. They used concept-mapping
      techniques to conduct a systematic analysis of the qualitative information
      generated from their focus group participants. Their findings emphasize the need
      for targeted resources for college students and the importance of using students'
      suggestions in developing nutrition programs.

PMID- 15495885
TI  - An innovative program to fund health-oriented student projects and research.
AB  - The price of a university education has increased over the years. As a result,
      students often graduate with thousands of dollars of debt. Conducting research or
      developing class projects that require personal expenditures can be overwhelming,
      if not impossible. Participation in research and in developing projects can
      enhance a student's educational experience. In an effort to address cost issues
      and provide an optimal learning experience for all students through participation
      in projects and research, the College of Health Sciences at the University of
      Texas at El Paso (UTEP) collaborated with a regional foundation to fund health
      oriented students' projects and research. Approximately 100 projects have been
      funded in amounts from 200 dollars to 10,000 dollars at UTEP. Similar programs
      can be replicated at other US universities. Establishing a general fund and
      identifying contributors may be a viable option, although finding a foundation or
      agency to fund the project poses a challenge.

PMID- 15495886
TI  - New meningococcal vaccine recommendations under consideration.

PMID- 15495887
TI  - Meningococcal education: more than just a vaccine.

PMID- 15495888
TI  - Time for renewal.
AB  - During hard economic times, college health professionals must urge their
      supervisors and administrators to help them maintain or find new funding so that
      they can attend regional and national conferences of the American College Health
      Association. In this viewpoint, a nurse from a small college shares the various
      sources of funding she discovered to enable her to attend regional and national
      conference of the American College Health Association that saved her from burnout
      and also motivated her to strive for changes through setting goals.

PMID- 15495889
TI  - Nursing-sensitive outcomes in cardiac surgery patients.
AB  - Achieving optimum patient outcomes has always been the primary focus of
      healthcare providers. The degree to which any healthcare discipline can impact
      outcomes varies since patient outcomes are multiple and diverse. As the
      measurement and reporting of outcomes has moved into the arena of public
      reporting, it has become essential for disciplines to be able to identify which
      outcomes they can either partially or completely influence. The focus of this
      article is to (1) identify what specific nursing-sensitive outcomes have been
      measured or monitored on cardiac surgery patients in the past and then (2)
      suggest potential next generation outcomes.

PMID- 15495890
TI  - Stroke outcome measures.
AB  - Stroke is the third leading cause of death and the foremost cause of adult
      neurological disability in the United States. Comprehensive assessment of persons
      with stroke is necessary for appropriate management of care and evaluation of
      interventions and outcomes. With the emergence of new effective treatments for
      stroke, the opportunity to document stroke impairments and disabilities to
      monitor recovery and to plan for reentry back to the community is a high nursing
      priority. The utilization of well-validated standardized instruments makes this
      goal attainable.

PMID- 15495891
TI  - Nursing outcomes in coronary heart disease.
AB  - Nursing research has contributed to our knowledge of patients with coronary heart
      disease (CHD), although much of the research has focused on acute cardiac events.
      Active and ongoing programs of research into CHD patient outcomes are essential
      as significant gaps remain. Consistently effective strategies to help patients
      change risk behaviors, recognize salient symptoms, manage their CHD and ischemic
      symptoms, improve function and quality of life, and prevent subsequent coronary
      events are needed, especially in the elderly and those with multiple
      comorbidities.

PMID- 15495892
TI  - Ventricular dysrhythmias: nursing approaches to health outcomes.
AB  - Cardiovascular nurses contribute significantly to health outcomes and frequently
      assume responsibility for the clinical and organizational processes to ensure
      positive outcomes for patients and families. In ventricular dysrhythmia
      populations, nurses have provided evidence for practices that influence outcomes
      and have studied patient outcomes related to mortality, morbidity, quality of
      life, psychological and physical functioning, symptoms, and family responses.
      Additionally, nurses have contributed to understanding organizational outcomes,
      such as costs and resource use related to patients with dysrhythmias. Most
      ventricular dysrhythmia outcome studies are descriptive. More intervention
      research is needed to develop a cohesive and comprehensive body of evidence upon
      which to base dysrhythmia nursing care to improve patient outcomes.

PMID- 15495893
TI  - State of the science for cardiovascular nursing outcomes: heart failure.
AB  - The incidence of heart failure is increasing because of the progressive aging of
      the population and improved survival from cardiovascular disease. This article
      synthesizes the state of the science of nurse sensitive outcomes in heart failure
      treated medically or surgically and provides recommendations for building the
      science. Outcomes studied include mortality, morbidity, resource use, quality of
      life, symptoms, physical function, return to work, and self-care and compliance
      behavior. Gaps in the literature are identified and recommendations for future
      research are provided.

PMID- 15495894
TI  - Insulin resistance syndrome.
AB  - Insulin resistance syndrome, also referred to as the metabolic syndrome, affects
      1 in 3 to 4 adults older than 20 years. This syndrome consists of a clustering of
      metabolic abnormalities that put people at risk for type 2 diabetes and
      cardiovascular disease. These clinical abnormalities include dyslipidemia,
      specifically elevated triglycerides and low high-density lipoprotein cholesterol,
      elevated glucose, and hypertension. The incidence of this morbid syndrome is
      expected to continue to grow both in the United States and worldwide, and thus is
      of tremendous interest to nurses seeking to measure their impact on patient
      outcomes. The key lifestyle interventions essential to treating this syndrome are
      weight loss and physical activity. The purpose of this article is to (1) describe
      the insulin resistance syndrome and discuss the current focuses for inquiry in
      major outcome areas (eg, mortality, morbidity, costs); (2) describe the status of
      specific lifestyle interventions (weight loss, diet, and exercise); (3) identify
      outcomes that nurses could measure to assess their impact on patient care; and
      (4) identify areas for future nursing research.

PMID- 15495895
TI  - Nursing outcomes: percutaneous coronary interventions.
AB  - Percutaneous coronary interventional (PCI) procedures are commonly performed in
      the United States. The process of caring for this patient population has changed
      dramatically over the last 10 years, with many of the changes being driven by an
      evolution in the knowledge base underlying nursing practice. The purpose of this
      article is to provide a summary and critique of nurse-sensitive outcomes related
      to patients undergoing PCI procedures and to identify gaps in the literature to
      provide recommendations for future research. Nursing research on indicators
      related to costs of care, morbidity, symptom management, functional status,
      patient/family knowledge, patient responses, behavior, and home/occupational
      function following PCI are discussed in this review.

PMID- 15495896
TI  - A public health action plan to prevent heart disease and stroke: the mandate for
      prevention across the continuum of care and across the lifespan.

PMID- 15495897
TI  - Nesiritide: practical approach and benefits in the outpatient setting.
AB  - Several trials have documented the efficacy of inpatient infusions of nesiritide
      in patients with heart failure. Early results from the Follow-Up Serial Infusions
      of Nesiritide (FUSION) study have supported the safety and efficacy of outpatient
      nesiritide infusions. Our Heart Failure Treatment Program began the use of
      outpatient nesiritide infusions to provide a cost-effective approach to improve
      quality of life in patients with advanced congestive heart failure not responding
      to standard therapy. We have provided outpatient nesiritide infusions for 2 years
      with favorable improvement in patient's quality of life and reduction in
      hospitalizations with no adverse outcomes demonstrated. Our experience utilizing
      nesiritide in the outpatient setting has been similar to the FUSION findings.

PMID- 15495898
TI  - An analysis of the time course of attention in preview search.
AB  - We used a probe dot procedure to examine the time course of attention in preview
      search (Watson & Humphreys, 1997). Participants searched for an outline red
      vertical bar among other new red horizontal bars and old green vertical bars,
      superimposed on a blue background grid. Following the reaction time response for
      search, the participants had to decide whether a probe dot had briefly been
      presented. Previews appeared for 1,000 msec and were immediately followed by
      search displays. In Experiment 1, we demonstrated a standard preview benefit
      relative to a conjunction search baseline. In Experiment 2, search was combined
      with the probe task. Probes were more difficult to detect when they were
      presented 1,200 msec, relative to 800 msec, after the preview, but at both
      intervals detection of probes at the locations of old distractors was harder than
      detection on new distractors or at neutral locations. Experiment 3A demonstrated
      that there was no difference in the detection of probes at old, neutral, and new
      locations when probe detection was the primary task and there was also no
      difference when all of the shapes appeared simultaneously in conjunction search
      (Experiment 3B). In a final experiment (Experiment 4), we demonstrated that
      detection on old items was facilitated (relative to neutral locations and probes
      at the locations of new distractors) when the probes appeared 200 msec after
      previews, whereas there was worse detection on old items when the probes followed
      800 msec after previews. We discuss the results in terms of visual marking and
      attention capture processes in visual search.

PMID- 15495899
TI  - Metamers in the haptic perception of heaviness and moveableness.
AB  - It is hypothesized that heaviness perception for a freely wielded nonvisible
      object can be mapped to a point in a three-dimensional heaviness space. The three
      dimensions are mass, the volume of the inertia ellipsoid, and the symmetry of the
      inertia ellipsoid. Within this space, particular combinations yield heaviness
      metamers (objects of different mass that feel equally heavy), whereas other
      combinations yield analogues to the size-weight illusion (objects of the same
      mass that feel unequally heavy). Evidence for the two types of combinations was
      provided by experiments in which participants wielded occluded hand-held objects
      and estimated the heaviness of the objects relative to a standard. Further
      experiments with similar procedures showed that metamers of heaviness were
      metamers of moveableness but not metamers of length. A promising conjecture is
      that the haptic perceptual system maps the combination of an object's inertia for
      translation and inertia for rotation to a perception of the object's
      maneuverability.

PMID- 15495900
TI  - Attentional selection of a peripheral ring overrules the central attentional
      bias.
AB  - In visual search, distractors that fall between fixation and the target are more
      disruptive than distractors that fall at the same eccentricity as the target
      (Wolfe, O'Neill, & Bennett, 1998). This sensitivity to the relative eccentricity
      of target and distractor elements originates from a space-based bias favoring
      stimuli closer to the fovea. We show that this spatial bias can be overruled by
      cuing attention to a ring-shaped object. We rule out various space-based
      explanations of these findings, including (1) attention to fronto-parallel planes
      in depth and (2) serial attention to different portions of a ring. We suggest
      that attentional selection of a ring-shaped object operates independently of, and
      can overrule, spatial biases in selection.

PMID- 15495901
TI  - The influence of head contour and nose angle on the perception of eye-gaze
      direction.
AB  - We report seven experiments that investigate the influence that head orientation
      exerts on the perception of eye-gaze direction. In each of these experiments,
      participants were asked to decide whether the eyes in a brief and masked
      presentation were looking directly at them or were averted. In each case, the
      eyes could be presented alone, or in the context of congruent or incongruent
      stimuli In Experiment 1A, the congruent and incongruent stimuli were provided by
      the orientation of face features and head outline. Discrimination of gaze
      direction was found to be better when face and gaze were congruent than in both
      of the other conditions, an effect that was not eliminated by inversion of the
      stimuli (Experiment 1B). In Experiment 2A, the internal face features were
      removed, but the outline of the head profile was found to produce an identical
      pattern of effects on gaze discrimination, effects that were again insensitive to
      inversion (Experiment 2B) and which persisted when lateral displacement of the
      eyes was controlled (Experiment 2C). Finally, in Experiment 3A, nose angle was
      also found to influence participants' ability to discriminate direct gaze from
      averted gaze, but here the effect was eliminated by inversion of the stimuli
      (Experiment 3B). We concluded that an image-based mechanism is responsible for
      the influence of head profile on gaze perception, whereas the analysis of nose
      angle involves the configural processing of face features.

PMID- 15495902
TI  - Different effects of eyelid blinks and target blanking on saccadic suppression of
      displacement.
AB  - Displacements of visual stimuli during saccadic eye movements are often not
      noticed. We have demonstrated that saccadic suppression of image displacement can
      be eliminated by blanking the stimulus for a short period during and after the
      saccade (Deubel, Schneider, & Bridgeman, 1996). Here we report an experiment in
      which target visibility was interrupted after the saccade, either by distal
      target blanking or by voluntary eyeblink. The data show that the effect of
      blinking is different from blanking; interruption of vision due to a blink did
      not enable subjects to detect target displacements any better than they had done
      in the no-blank condition. The results provide evidence for an extraretinal
      signal that distinguishes between endogenous and exogenous sources of temporary
      object disappearance after the saccade.

PMID- 15495903
TI  - Spectral tilt as a cue to word segmentation in infancy and adulthood.
AB  - Across a variety of tasks, adults respond differently to syllables with multiple
      stress cues than to syllables with only one cue to stress. This series of
      experiments was designed to explore how infants and adults use partial stress as
      a cue to word boundaries. In the first experiment, 9-month-old infants treated
      syllables with only one cue to stress (spectral tilt) as a strong cue to word
      boundaries. The second experiment shows that whereas adults treat syllables with
      multiple cues to stress as word onsets, they do not consider syllables marked
      only by spectral tilt to be strong indicators of word boundaries. Thethird
      experiment shows that 1-year-old infants are more adultlike than 9-month-olds in
      their use of stress cues. Taken together, these results suggest a rapid
      development of stress cue knowledge in infancy, perhaps due to infants'
      experience with word segmentation.

PMID- 15495904
TI  - The effects of global grouping laws on surface lightness perception.
AB  - Previous studies of lightness perception have shown that local surface grouping
      laws such as proximity and T junction were powerful determinants of target
      surface lightness. Recent lightness theories also emphasize the importance of
      local grouping of surfaces. In this study, we further examined the effects of
      three global grouping laws--symmetry, repetition, and alternation--on lightness
      perception. Local surface grouping laws such as proximity and good continuation
      were controlled across all of our stimulus displays. Participants' lightness
      perception consistently depended on a given surface's belongingness as determined
      by these laws--that is, global grouping laws affected a target surface's
      lightness perception. Our results indicate that global grouping laws determine a
      target surface's lightness when local surface grouping does not produce any
      distinct surface belongingness. Implications of our basic results are discussed
      in terms of a recent lightness theory.

PMID- 15495905
TI  - Sustained change blindness to incremental scene rotation: a dissociation between
      explicit change detection and visual memory.
AB  - In a change detection paradigm, the global orientation of a natural scene was
      incrementally changed in 1 degree intervals. In Experiments 1 and 2, participants
      demonstrated sustained change blindness to incremental rotation, often coming to
      consider a significantly different scene viewpoint as an unchanged continuation
      of the original view. Experiment 3 showed that participants who failed to detect
      the incremental rotation nevertheless reliably detected a single-step rotation
      back to the initial view. Together, these results demonstrate an important
      dissociation between explicit change detection and visual memory. Following a
      change, visual memory is updated to reflect the changed state of the environment,
      even if the change was not detected.

PMID- 15495906
TI  - Temporal interval production and short-term memory.
AB  - Interference with time estimation from concurrent nontemporal processing has been
      shown to depend on the short-term memory requirements of the concurrent task
      (Fortin & Breton, 1995; Fortin, Rousseau, Bourque, & Kirouac, 1993). In
      particular, it has been claimed that active processing of information in short
      term memory produces interference, whereas simply maintaining information does
      not. Here, four experiments are reported in which subjects were trained to
      produce a 2,500-msec interval and then perform concurrent memory tasks.
      Interference with timing was demonstrated for concurrent memory tasks involving
      only maintenance. In one experiment, increasing set size in a pitch memory task
      systematically lengthened temporal production. Two further experiments suggested
      that this was due to a specific interaction between the short-term memory
      requirements of the pitch task and those of temporal production. In the final
      experiment, subjects performed temporal production while concurrently remembering
      the durations of a set of tones. Interference with interval production was
      comparable to that produced by the pitch memory task. Results are discussed in
      terms of a pacemaker-counter model of temporal processing, in which the counter
      component is supported by short-term memory.

PMID- 15495907
TI  - Mandarin speech perception by ear and eye follows a universal principle.
AB  - In this study, the nature of speech perception of native Mandarin Chinese was
      compared with that of American English speakers, using synthetic visual and
      auditory continua (from /ba/ to /da/) in an expanded factorial design. In
      Experiment 1, speakers identified synthetic unimodal and bimodal speech syllables
      as either /ba/ or /da/. In Experiment 2, Mandarin speakers were given nine
      possible response alternatives. Syllable identification was influenced by both
      visual and auditory sources of information for both Mandarin and English
      speakers. Performance was better described by the fuzzy logical model of
      perception than by an auditory dominance model or a weighted-averaging model.
      Overall, the results are consistent with the idea that although there may be
      differences in information (which reflect differences in phonemic repertoires,
      phonetic realizations of the syllables, and the phonotactic constraints of
      languages), the underlying nature of audiovisual speech processing is similar
      across languages.

PMID- 15495908
TI  - The use of a distractor-assigned response slows later responding in a location
      negative priming task.
AB  - Responding to a target's location takes longer when that location has recently
      contained a distractor event (ignored-repetition [IR] trial) relative to when it
      has been unoccupied (control trial). This is known as the location negative
      priming (NP) effect. We aimed to determine whether the elevated reaction time
      observed for IR trials was due to the reuse of a distractor location (location
      locus) and/or to the need to execute a (just inhibited) distractor response
      (response locus). We isolated these loci latency effects by using many-to-one and
      one-to-many location-response assignments. Our results showed that reusing a
      distractor location hastened target processing at that position (facilitative
      location locus), whereas the production of a distractor response was associated
      with a time cost (interfering response locus). Accordingly, part of the latency
      elevation seen with IR trials results from the need on these occasions to execute
      ajust inhibited (distractor) response, and, hence, the location NP effect has a
      response locus.

PMID- 15495909
TI  - Unconscious perception: a model-based approach to method and evidence.
AB  - Unconscious perceptual effects remain controversial because it is hard to rule
      out alternative conscious perception explanations for them. We present a novel
      methodological framework, stressing the centrality of specifying the single
      process conscious perception model (i.e., the null hypothesis). Various
      considerations, including those of SDT (Macmillan & Creelman, 1991), suggest that
      conscious perception functions hierarchically, in such a way that higher level
      effects (e.g., semantic priming) should not be possible without lower level
      discrimination (i.e., detection and identification). Relatedly, alternative
      conscious perception accounts (as well as the exhaustiveness, null sensitivity,
      and exclusiveness problems-Reingold & Merikle, 1988, 1990) predict positive
      relationships between direct and indirect measures. Contrariwise, our review
      suggests that negative and/or nonmonotonic relationships are found, providing
      strong evidence for unconscious perception and further suggesting that conscious
      and unconscious perceptual influences are functionally exclusive (cf. Jones,
      1987), in such a way that the former typically override the latter when both are
      present. Consequently, unconscious perceptual effects manifest reliably only when
      conscious perception is completely absent, which occurs at the objective
      detection (but not identification) threshold.

PMID- 15495910
TI  - Valid distinctions between conscious and unconscious perception?
AB  - In this commentary, we discuss the strengths and limitations of Snodgrass,
      Bernat, and Shevrin's (2004) theory of unconscious perception. Our commentary
      centers on the value of signal detection theory (SDT) to understanding the
      unconscious perception controversy, a value that Snodgrass et al. for the most
      part agree with (i.e., that most approaches to studying unconscious perception
      are invalid because they have confounded the criterion for detection with the
      criterion for awareness). However, we believe that their model relies on a
      somewhat restricted application of SDT. We discuss how SDTcan be better applied
      to provide the necessary tests to validate their model.

PMID- 15495911
TI  - Unconscious perception: the need for a paradigm shift.
AB  - According to Snodgrass, Bernat, and Shevrin (2004), unconscious perception can be
      demonstrated convincingly only at the objective detection threshold, provided
      that the conditions of their objective detection/strategic model are met, whereas
      both the subjective threshold model of Cheesman and Merikle (1984, 1986) and the
      objective threshold/rapid decay model of Greenwald, Draine, and Abrams (1996) are
      inconclusive. We argue on theoretical, metatheoretical, and empirical grounds
      that all three dual-process models, which are based on both conscious and
      unconscious perception, should be rejected in favor of the single-process
      conscious perception model.

PMID- 15495912
TI  - Unconscious perception and the classic dissociation paradigm: a new angle?
AB  - Reingold and Merikle's (1988, 1990) critique of the classic dissociation paradigm
      identified the exhaustiveness, exclusiveness, null sensitivity, and task
      comparability issues as inherent problems that severely undermine the utility of
      this paradigm. Snodgrass, Bernat, and Shevrin (2004) attempt to provide solutions
      to these problems and claim to propose a novel conceptual and methodological
      framework for the study of unconscious perception. Unfortunately, the present
      analysis indicates that the approach proposed by Snodgrass et al. involves the
      same problems as do previous implementations of the classic dissociation
      paradigm.

PMID- 15495913
TI  - Turning research into practice: cases on adopting evidence-based innovations for
      everyday care.
AB  - Turning clinical research and innovations into actual practices that enhance
      quality care--at both the hospital level and the health system level--can be
      challenging. But many organizations are finding creative ways to get those ideas
      on the front line.

PMID- 15495914
TI  - Lessons on speeding up adoption of research into everyday practice.
AB  - Many evidence-based programs and interventions have been adopted into clinical
      practice only partially if at all. But several successful clinical programs
      highlight lessons to be learned to make those practices reality.

PMID- 15495915
TI  - 10-year outline unveiled to roll out health information technology.
AB  - The Secretarial Summit on Health Information Technology unveiled a 10-year plan
      to develop a national electronic health infrastructure.

PMID- 15495916
TI  - 195,000 annual deaths linked to in-hospital errors, study says.
AB  - Approximately 195,000 people in the United States died from potentially
      preventable in-hospital medical errors--or double the highest number estimated by
      the Institute of Medicine in its 1999 landmark report--in 2000, 2001, and 2002,
      according to a new study of 37 million patient records.

PMID- 15495918
TI  - Perspectives: Payment, the uninsured loom large in specialty-hospital debate.

PMID- 15495917
TI  - New public, private initiatives will enroll more in drug card.

PMID- 15495919
TI  - Lewin estimate of Kerry health plan doubles campaign's fiqure.

PMID- 15495920
TI  - Panel: racism, cost keep minorities out of health professions.

PMID- 15495923
TI  - New report on nursing education programs will allow progress to be tracked.

PMID- 15495925
TI  - [Evaluation of the performance to date of the BHV-1 eradication campaign in
      Saxony-Anhalt (Germany)].
AB  - The present article is attempting to evaluate the to date performance of the BHV
      1 eradication campaign currently run in Saxony-Anhalt. Special emphasis is put on
      the modelling of missing data and an optimum performance--for comparison with the
      observed progress of eradication. The eradication campaign turned out to have
      performed almost optimally so far, but problems might arise in its final phase
      due to insular management deficiencies and violation of laws, as well. Possible
      sanctions are mentioned.

PMID- 15495926
TI  - The spatial and temporal disappearance of different oral rabies vaccine baits.
AB  - Bait disappearance can give valuable information for the assessment of oral
      vaccination campaigns of foxes against rabies. In this study, the spatial and
      temporal disappearance of three different vaccine baits under almost identical
      conditions was investigated. In the study area, 350 baits were placed at
      previously marked positions during two different periods; late autumn and early
      spring. The distribution of baits was in accordance with the method as
      recommended by the European Union; a density of 20 baits per km2 along flight
      lines 500m apart. Bait disappearance was checked 1, 3, 5 and 7 days after
      distribution. At least 80% of the baits had disappeared within one week after
      distribution. No difference in bait disappearance was observed between the two
      selected periods. However, a significant higher bait disappearance was observed
      in forested areas when compared to open agricultural areas. Furthermore, the
      differences in bait disappearance between the three type of baits tested were
      relatively small and not significant.

PMID- 15495927
TI  - [Pasteurella: insights into the virulence determinants of a heterogenous
      bacterial type].
AB  - Pasteurella (P.) multocida is the causative agent of numerous economically
      relevant diseases worldwide. These are enzootic bronchopneumonia in cattle and
      sheep and hemorraghic septicemia in cattle and buffaloes, Rhinitis atrophicans in
      swine, snuffles in rabbit, and fowl cholera. All disease complexes are associated
      with certain capsular and somatic antigens. Even as human pathogen P. multocida
      is of increasing importance, causing wound infections, and even septicemia,
      meningitis, and endocarditis. Despite extensive research activities including the
      genome analysis of one fowl cholera isolate in the year 2001 there are a lot of
      open questions concerning the molecular pathogenic mechanisms. Problems
      encountered are the high antigenic variability and the wide host spectrum of P.
      multocida as well as different courses of infection. In consequence there are
      enormous difficulties in producing vaccines. Transcriptomics and proteomics
      hopefully will give new insight into the pathogenesis of P. multocida infections
      in different hosts. A frequent problem particular in classical diagnostic
      laboratories is the diagnosis of P. multocida and its differentiation from other
      P. species and Mannheimia (M.) haemolytica. The biochemical identification of P.
      multocida is not reliable due to variable phenotypical characteristics often
      caused by different culture conditions, and it is time consuming and cost
      intensive. Extensive molecular biologic studies concerning the prevalence and
      distribution of virulence associated genes known so far in P. species, which will
      be described in detail in this paper, could contribute to the establishment of a
      diagnostic tool, such as a multiplex polymerase chain reaction, that would
      provide a cheap and time-saving identification and characterization of wildtype
      strains.

PMID- 15495928
TI  - [The use of macrolides, lincomycin and tiamulin as animal feed drugs for pigs in
      Schleswig-Holstein].
AB  - An evaluation of production orders for medicated feedingstuffs for pigs given in
      1998 in Schleswig-Holstein showed macrolides, lincomycin and tiamulin as
      frequently used antibiotical ingredients. The presented study analyses the
      production orders which include macrolides, lincomycin or tiamulin in more
      detail. There were large deviations to the rules of good clinical practise for
      the use of antibiotics (2000). The applied dosage was often lower than suggested
      in the literature.

PMID- 15495929
TI  - [The use of sulfonamides and sulfonamide/trimethoprim combinations as animal feed
      drugs for pigs in Schleswig-Holstein].
AB  - An evaluation of production orders for medicated feedingstuffs for pigs given in
      1998 in Schleswig-Holstein showed sulphonamides and combinations of sulphonamides
      and trimethoprim as frequently used antibiotical ingredients. The presented study
      analyses the production orders which include sulphonamides and combinations of
      sulphonamides and trimethoprim in more detail. There were large deviations to the
      rules of good clinical practise for the use of antibiotics. The applied dosage
      was often lower than suggested in the literature.

PMID- 15495930
TI  - [The use of aminoglycosides, colistin and beta-lactam antibiotics as animal feed
      drugs for pigs in Schleswig-Holstein].
AB  - An evaluation of production orders for medicated feedingstuffs for pigs given in
      1998 in Schleswig-Holstein showed aminoglycosides, colistin and beta-lactam
      antibiotics as regularly used antibiotical ingredients. The presented study
      analyses the production orders which include these antibiotics more in detail
      particularly with regard to the prescribed dosages. In part, there were
      deviations to the rules of good clinical practise for the use of anitbiotics. The
      applied dosage of spectinomycin and apramycin was often lower than suggested in
      the literature. The low oral bioavailability of amoxicillin was not considered
      when using amoxicillin in medicated feedingstuffs.

PMID- 15495931
TI  - [Screening for antibodies against zoonotic agents among employees of the
      Zoological Garden of Vienna, Schonbrunn, Austria].
AB  - The aim of this study was to investigate the prevalence of antibodies against
      zoonotic agents in employees of the zoological garden of Vienna, Schonbrunn,
      Austria. Sixty out of 120 employees participated in the study. In 97% of them
      antibodies to at least one zoonotic agent were identified. Only two participants
      were free of antibodies to the zoonotic agents tested. The following
      seroprevalences (in brackets) were obtained: Viral zoonotic (and potentially
      zoonotic) agents: Influenzavirus A/H1N1 (58%), Influenzavirus A/H3N2 (85%),
      Lymphocytic choriomeningitis virus (13%), Encephalomyocarditis virus (5%),
      Orthopox- (Cowpox-) virus and Hantavirus type Puumala (3%). Hantavirus type
      Hantaan and Borna disease virus (all negative). Bacterial zoonotic agents:
      Bartonella henselae (65 %), Borrelia burgdorferi (10%), Leptospira interrogans
      serovar copenhageni and serovar icterohaemorrhagiae as well as Chlamydophila
      psittoci (2% each). Brucella spp., Coxiella bumetii, and Francisella tularensis
      (all negative). Parasitic zoonotic agents: Toxoplasma gondii (53%), Toxocara spp.
      (21%), Capillaria hepatica (2%), Fasciola hepatica, Schistosoma mansoni, E.
      multilocularis, and E. granulosus (all negative). The remarkably high
      seroprevalence to the causative agent of cat scratch disease, Bartonella
      henselae, is probably due to the private contact of the employees to cats.
      Regarding viral zoonotic agents it has to be mentioned that Influenzavirus
      vaccination and/or human-to-human transmission of especially A/H3N2
      Influenzaviruses probably attributed significantly to the very high
      seroprevalence to both Influenzavirus types A/H1N1 and A/H3N2. When investigating
      parasitic zoonotic agents, high prevalence rates were found against Toxoplasma
      gondii and Toxocara spp., however, it was not possible to establish a causal link
      between seropositivity and the professional activity in the zoo. Interestingly,
      in the case of antibodies to T. gondii, the typical correlation with age was not
      found in this study, while in the case of the Toxocara spp. positive subjects a
      correlation was identified with both age and duration of employment in the zoo.
      Regarding the later two zoonotic parasites, employees of the zoological garden
      showed significantly higher seroprevalences than the average Austrian population.
      Antibodies to Capillaria hepatica, a hepatic-parasite in rodents which is
      diagnosed in humans rarely, were identified in one employee and another one
      showed a questionable positive result. Further investigations did not exhibit
      clinical infestations with the parasite in these two individuals so far.

PMID- 15495932
TI  - Comparison of conventional coproscopical methods and commercial coproantigen
      ELISA kits for the detection of Giardia and Cryptosporidium infections in dogs
      and cats.
AB  - Faecal samples of 270 dogs and 100 cats from 3 animal shelters in Germany were
      comparatively examined using conventional coproscopical methods and commercial
      coproantigen ELISA kits for the detection of Giardia and Cryptosporidium
      infections. Giardia cysts were found in 9.5% and 0% of the faecal samples in dogs
      and cats, respectively, examined once using the ZnCl2-NaCl flotation. However,
      the Giardia coproantigen ELISA (ProSpecT Giardia Microplate Assay) was positive
      in 29.5% and 22.4% of the samples from dogs and cats, respectively. Direct faecal
      smears stained with carbol fuchsin showed Cryptosporidium oocysts in one dog
      (0.4%) and one cat (1%). In contrast, the Cryptosporidium coproantigen ELISA
      (ProSpecT Cryptosporidium Microplate Assay) reacted positively in 23% of the
      samples from dogs and 30% of the samples from cats. Both coproantigen ELISAs were
      more often positive in coproscopically Giardia-negative canine faecal samples
      that contained Isospora burrowsi/ohioensis oocysts than in faecal samples without
      any parasite stage. Possible reasons for these observations are discussed.

PMID- 15495933
TI  - [Genotype effects of milk protein polymorphisms on milk production in East
      Friesian dairy sheep].
AB  - The frequencies of milk protein variants alphas1-casein, alphas2-casein, beta
      casein and beta-lactoglobulin were determined in 182 milk sheep from 7 flocks in
      Lower Saxony and Saxony. The genotype effects of these polymorphic milk protein
      variants on milk performance traits were estimated for 173 ewes using a test day
      model with fixed regression.The model included the fixed effects of colour
      variant of the breed, region, lambing season, lambing year, lactation number and
      number of lambs born. The herd and animal effect were treated as random and the
      days in milk as linear and non-linear covariates. The milk protein variants of
      alphas1-casein and beta-casein showed a significant relationship to protein
      content and the variants of beta-casein to milk fat content. Milk fat yield was
      significantly associated with the milk protein variants of alphas2-casein,
      whereas the other milk performance traits were not significantly correlated.

PMID- 15495934
TI  - [Evaluation of a modified exogenous creatinine clearance as a suitable renal
      function test for the small animal practice].
AB  - A suitable method in the routine veterinary practice for the quantitative
      determination of the glomerular filtration rate (GFR) in dogs and cats has not
      been available until to date. Therefore, we modified the known plasma clearance
      model (=P-CL). The resulting P-CLterminal was assessed concerning its diagnostic
      value. P-CL of exogenous creatinine (P-CLcrea) and of inulin were determined in
      dogs (n=12, Beagle, 6 months of age) and cats (n=11, Domestic Short Hair, 14
      months of age). The marker substances were administered as a bolus injection. In
      fasted dogs, P-CLcrea was 84.3 +/- 14.85 ml/min/m2 after a creatinine dose of 2.4
      g/m2. An electrolyte infusion during the clearance determination did not alter
      the resulting values (p>0.05). In fasted cats, P-CLcrea was 54.7 +/- 5.8
      ml/min/m2 (creatinine dose 2.0 g/m2). The inulin clearance, determined at the
      same time, was 104.5 +/- 19.81 ml/min/m2. Feeding the cats just before and during
      the test increased P-CL of both markers significantly (p<0.05). In order to adapt
      the clearance method for diagnostic assessment of GFR in the small animal
      practice, we aimed at minimizing the number of required blood samples (3 instead
      of 7 or more) and introduced the modified exogenous creatinine clearance (P
      CLterminal). These values determined were 108.4 +/- 20.81 ml/min/m2 in fasted
      dogs and 66.3 +/- 11.81 ml/min/m2 in fasted cats. An electrolyte infusion (dogs)
      and feeding (cats) had the same effect on P-CLterminal values as described above
      for P-CL. In conclusion,the modified exogenous creatinine clearance is a suitable
      renal function test for the early diagnosis of renal disease in dogs and cats
      presented in small animal practices.

PMID- 15495935
TI  - [Treatment of infected wounds and abscesses in bovine limbs with Ligasano
      polyurethane-soft foam dressing material].
AB  - The objective of this report is to present the most important indications for the
      use of Ligasano-polyurethane-soft-foam dressing material in the treatment of
      infected wounds in cattle. For this study, 28 cattle were selected, which were
      treated at the clinic (2000-2003) for infected cut, puncture and laceration
      wounds on the limbs, purulent tarsal hygromas, large abscesses in the tarsal,
      crural and thigh regions, and purulent tenosynovitis of the digital flexor tendon
      sheath caused by penetrating puncture wounds. After routine wound cleansing,
      debridement or adequate surgery with wound lavage, Ligasano-polyurethane-soft
      foam (Ligamed Medical Produkte, Cadolzburg-Wachendorf, Germany) was applied as a
      primary wound dressing instead of the conventional cotton gauze swabs or as
      drainage material in all these wounds. The porous surface structure of this
      material caused subtle wound debridement and mechanical stimulation of the wound
      surface increasing exudation and decreasing fibrinous adhesions. The pores
      ensured good drainage, reduced infection, avoided the accumulation of exudate and
      the following destruction of the wound surface. In all these indications, except
      abscesses and purulent hygromas, no or only slight purulent exudation of the
      treated wounds was observed. Especially in the treatment of purulent
      tenosynovitis of the digital flexor tendon sheath with tendon resection a rapid
      healing of these large surgical wounds--often within 2 weeks--was found. The
      therapeutic effect of Ligasano-polyurethane-soft-foam as a primary wound dressing
      was so convincing in these bovine patients, that it is now used exclusively as
      primary wound dressing material for treatment of infected wounds.

PMID- 15495936
TI  - [Eyelid drooping: diagnosis on the basis of an algorithm].
AB  - Five patients presented with eyelid drooping (blepharoptosis). A 26-year-old man
      with oculomotor disorders without anisocoria and a slow progressive course
      without fluctuations had a myogenic condition. His diplopia was alleviated by
      prism glasses. Surgical correction of the ptosis was planned. An 81-year-old man
      in whom the symptoms showed a course that varied over time had a disordered
      neuromuscular transmission that responded well to pyridostigmine. A 57-year-old
      man with oculomotor disorders and a dilated pupil on the affected side had an
      injury to the oculomotor nerve (and other cranial nerves), which remained stable
      after endovascular treatment of the causative aneurysm. A 22-year-old man had a
      constricted pupil (Horner's syndrome) and pain in the head and neck due to
      dissection of the internal carotid; his symptoms disappeared spontaneously. A 34
      year-old woman had an isolated ptosis due to detachment of the aponeurosis of the
      M. levator palpebrae superioris following the chronic use of hard contact lenses;
      she was advised as to how to remove the lenses cautiously, to prevent further
      detachment. Eyelid drooping can have many causes. A systematic arrangement of the
      information gathered by a careful medical history and neurological examination
      often provides a reasonably accurate indication of the possible causes of the
      complaints.

PMID- 15495937
TI  - [The progestagen-containing implant (Implanon); who is responsible for what?].
AB  - Implanon is a contraceptive device with a high reliability in the prevention of
      pregnancy. The insertion is a simple procedure but the physician must master this
      skill. A number of cases have been recorded in which the rod appeared to have
      disappeared, which sometimes led to an unwanted pregnancy and sometimes ended in
      claims for compensation. There are a number of tips the physician can use to make
      sure that the insertion is done properly. At present, training in the insertion
      of this device is only offered by the company that sells Implanon. The question
      arises whether the professional group of GP's or gynaecologists should take over
      this responsibility.

PMID- 15495938
TI  - [Blockade of chemokines in chronic inflammatory diseases].
AB  - Chemokines form a relatively new family of chemotactic cytokines that seem to
      play a central role in the migration and activation of leukocytes in a wide
      variety of immune-mediated disorders. Specific therapy targeted against these
      proteins may well become an effective treatment in many of these disorders. The
      efficacy and safety of chemokine blockade is currently being investigated in
      clinical trials on patients with HIV infection, multiple sclerosis, rheumatoid
      arthritis and other chronic inflammatory disorders. The first results have been
      reported in patients with rheumatoid arthritis and these seem to confirm the
      potency of this treatment.

PMID- 15495939
TI  - [The increase in pneumonia-related morbidity and mortality among adults in the
      Netherlands and possible explanations for it].
AB  - As seen in several national registration systems, the morbidity and mortality due
      to pneumonia-related disease has increased in the Netherlands in the past 10
      years. It is unlikely that the observed increase in mortality due to pneumonia is
      purely the result of the registration system used or misclassification. An
      increase in the elderly population is the most likely, albeit only partial,
      explanation. An increase in underlying diseases such as chronic obstructive
      pulmonary disease and diabetes mellitus is also a possible explanation. Increased
      antibiotic resistance, inadequate treatment or a shift in the spectrum of micro
      organisms causing pneumonia are less likely explanations. Reducing the morbidity
      and mortality due to pneumonia demands an integrated approach aimed at elderly
      patients or patients with co-existing disease and executed by specialists in the
      fields of geriatrics, internal medicine, pulmonary disease and infectious
      diseases.

PMID- 15495940
TI  - [Diagnostic image (205). A neonate with much yellow amniotic fluid].
AB  - A neonate was born prematurely with polyhydramnios and yellow amniotic fluid. He
      developed gastric retention and bilious vomiting. Abdominal rontgenography showed
      jejunum atresia.

PMID- 15495941
TI  - [From gene to disease; dopamine-beta-hydroxylase deficiency and orthostatic
      hypotension].
AB  - The DBH gene encodes dopamine-beta-hydroxylase (DbetaH), the enzyme that
      catalyses the formation of norepinephrine from dopamine. Inactivation of this
      enzyme due to a mutation of the DBH gene causes a selective (nor)-adrenergic
      failure of the sympathetic nervous system. This manifests as a severe orthostatic
      syndrome in which sweating and a normal parasympathetic function are preserved.
      Several mutations of the DBH gene that cause this very rare syndrome have now
      been identified. Diagnosis is made on the basis of clinical features and the
      finding of increased plasma dopamine in the near-absence of norepinephrine. A
      sole finding of absent plasma DbetaH is insufficient, since about 4% of the
      population have absent DbetaH. This trait cosegregates with a polymorphism in the
      promoter region of the DBH gene and is not associated with sympathetic failure.
      The orthostatic syndrome of DbetaH deficiency can be treated with the non-natural
      amino acid L-dihydroxyphenylserine, which is decarboxylated to norepinephrine by
      the ubiquitous aromatic-L-amino acid decarboxylase.

PMID- 15495942
TI  - [No major difference between population screening for cervical carcinoma at the
      present screening interval of 5 years and the former interval of 3 years].
AB  - OBJECTIVE: To assess the effect of extending the screening interval from 3 to 5
      years on the detection of premalignant changes and invasive cervical carcinoma in
      the restructured population screening programme. DESIGN: Retrospective follow-up
      study. METHOD: The results were collected of the 1st round (1996-2000; 277, 377
      women) and a part of the 2nd round (2001; 49,622 women; screening interval: 5
      years) of the screening programme in Region West, the Netherlands. Histoscores
      for cervical intraepithelial neoplasia (CIN) 3 and squamous cell carcinoma (n/100
      women investigated) and the hit count (sum of the histoscores for CIN 3,
      adenocarcinoma in situ and (micro)invasive cervical carcinoma) were calculated.
      Data of women with adenocarcinoma in situ and endocervical (adeno)carcinoma were
      recorded separately. The results of the 1st and 2nd round of the current
      screening programme (commenced in 1996) were compared with those of the
      historical screening programme that commenced in 1976 (screening interval: 3
      years). RESULTS: From the 1st to the 2nd round of the historical screening
      programme that commenced in 1976, the histoscores for CIN 3 (3.33, 1.88) and
      squamous cell carcinoma (0.53, 0.19) and the hit count (3.92, 2.15) all
      diminished significantly. The current restructured programme, which commenced in
      1996, showed low starting values for all three parameters, comparable to those in
      the 2nd round of the 1976 programme; a further reduction (0.16, 0.08; p < 0.01)
      was seen only in the histoscore for squamous cell carcinoma. In both rounds of
      both programmes, the histoscores for adenocarcinoma in situ (0.02, 0.02, 0.05,
      0.04, respectively) and endocervical adenocarcinoma (0.04, 0.06, 0.05, 0.04)
      remained stable. CONCLUSION: In the current cervical carcinoma screening
      programme, with a screening interval of 5 years, the hit count of serious
      abnormalities remained constant while the incidence of squamous cell carcinoma
      decreased; this is in contrast to the historical screening programme (commenced
      in 1976), when both the hit count and the histoscore for CIN 3 diminished
      significantly. There were indications that cervical screening has no beneficial
      effect on the prevention of cervical adenocarcinoma.

PMID- 15495944
TI  - [Two sisters with progressive familial intrahepatic cholestasis].
AB  - A few months after birth two sisters aged 5 and 9 years had developed cholestasis
      and abnormal liver functions with symptoms including itching and jaundice. The
      younger sister also developed rickets and clotting disorders. On clinical,
      biochemical and immunohistopathological grounds the diagnosis of 'progressive
      familial intrahepatic cholestasis (PFIC) type 2' was made. Medical treatment was
      not succesfull in reducing symptoms. An ileocolonic bypass in the younger child
      was not effective. Subsequently, both patients underwent partial external biliary
      diversion (PEBD). Except for a period of intermittent itching in the younger
      child, both patients remained free of symptoms 2 years after PEBD. In cases where
      an early diagnosis is made, PEBD could delay or even prevent the necessity of
      liver transplantation.

PMID- 15495943
TI  - [Two patients with a non-palpable, subcutaneously implanted contraceptive].
AB  - Two women, 33 and 31 years of age, were referred to a surgeon for the removal of
      a previously implanted hormonal contraceptive after the general practitioner had
      attempted this without success. However, no foreign body could be detected in
      either patient by surgery, echography and MRI and by X-ray, echography and MRI,
      respectively. They were then referred to a gynaecologist. In the first patient, a
      low level of etonogestrel confirmed that there was no contraceptive in her body.
      Subcutaneous contraceptives are sometimes implanted incorrectly. If the rod is
      not palpable at the site of insertion, then the etonogestrel level should be
      determined first of all. If the hormone level indicates that a rod is indeed
      present, then echography or MRI may be considered to localise it before resorting
      to surgical exploration. Many problems can be prevented by proper implantation.

PMID- 15495945
TI  - [Obstructive jaundice after surgery of the biliary tract: a benign stricture or
      not?].

PMID- 15495946
TI  - [Surveillance of hepatitis A in the Netherlands 1993-2002].

PMID- 15495947
TI  - [Clinical reasoning and decision-making in practice. A 23 year old woman with
      malaise, anorexia and behavior changes].

PMID- 15495948
TI  - [Congress of the European Urology Association 2004: state and perspective of
      prostate cancer management].

PMID- 15495949
TI  - Electrokinetic removal of chromium and copper from contaminated soils by lactic
      acid enhancement in the catholyte.
AB  - The electrokinetic removal of chromium and copper from contaminated soils by
      adding lactic acid in cathode chamber as an enhancing reagent was evaluated. Two
      sets of duplicate experiments with chromium contaminated kaolinite and with a
      silty soil sampled from a superfund site in California of USA and polluted by Cr
      and Cu, were carried out in a constant current mode. Changes of soil water
      content and soil pH before and after the electrokinetic experiments, and
      variations of voltage drop and electroosmosis flow during the treatments were
      examined. The results indicated that Cr, spiked as Cr( VI ) in the kaolinite, was
      accumulated mainly in the anode chamber, and some of Cr and metal hydroxides
      precipitated in the soil sections in contact with the cathode, which
      significantly increased electrical energy consumption. Treatment of the soil
      collected from the site showed accumulation of large amounts of Cr and Cu in the
      anode chamber while none was detected in the cathode one. The results suggested
      that the two metals either complexed with the injected lactic acid at the cathode
      or existed as negatively charged complex, and electromigrated toward the anode
      under a voltage gradient.

PMID- 15495950
TI  - Observations on carbon and nitrogen content of suspended matter in a headwater
      stream in Hong Kong.
AB  - The total carbon(C) and total nitrogen(N) content of suspended matter in a small
      undisturbed headwater drainage basin in the New Territories of Hong Kong has been
      monitored. Mean C and N contents were 12.85% and 0.99% respectively for 132
      samples. Samples collected under stableflow conditions had mean C and N contents
      of 12.81% and 1.06% respectively. Stormflow samples had mean C and N values of
      12.86% and 0.97% respectively, which were very similar to the levels observed
      under stableflow conditions. The mean C:N ratios of 12.47 and 13.39 for
      stableflow and stormflow also reveal little difference according to hydrologic
      conditions. When all the data is considered little difference is observed in C
      and N according to the season. However, in winter there is a significant
      difference in C and N content between stable and stormflow samples. When C and N
      are plotted against water level the scattergraphs suggested that as stage
      increases the percentage of C and N in the suspended matter declines.
      Scattergraphs of C and N against suspended sediment concentration reveal a
      negative association. Comparison has been made between fresh leaf C, N and C/N
      ratio for trees and shrubs and the suspended matter. Fresh leaves do not appear
      to contribute significantly to suspended matter. The C/N ratio of suspended
      matter would also seem to exclude woody material and algae as sources of
      suspended matter.

PMID- 15495951
TI  - Photochemistry of insecticide imidacloprid: direct and sensitized photolysis in
      aqueous medium.
AB  - The direct and sensitized photodegradations of imidacloprid, 1-(6-chloro-3
      pyridinylmethyl)-N-nitro-2-imidazolidinimine, were investigated in aqueous
      solution and with and without various photo-sensitizers. Results of the study
      revealed that the intensity of lamp-house and irradiation wavelength had
      significant effects on the photolysis of imidacloprid. Complete degradation of 20
      mg/L imidacloprid in aqueous phase was observed in 40 min under ultraviolet( UV)
      irradiation system, suggesting the ultraviolet ray played significant role in
      direct photolysis of imidacloprid. The additions of various photo-sensitizers
      lead to improve the degradation efficiency of imidacloprid under the irradiation
      of black light fluorescent lamp. TiO2 was the most efficient in the photo
      catalytic degradation of imidacloprid among other photo-sensitizers in used this
      study. However, addition of acetone inhibited the photolysis of imidacloprid
      under the irradiation of UV, indicating the occurrence of competition between
      acetone and imidacloprid for photos. Mineralization of the imidacloprid was
      examined to clarify the final photochemical degradation products of the
      insecticide which were CO2, Cl- and NO3-. Complete photo-oxidation of nitrogen to
      NO3- occurred very slowly via the intermediate formation of NH4+ and NO2-.

PMID- 15495952
TI  - Decomposition characteristics of toluene by a corona radical shower system.
AB  - Non-thermal plasma technologies offer an innovative approach to decomposing
      various volatile organic compounds(VOCs). The decomposition of toluene from
      simulated flue gas was investigated using a pipe electrode with nozzles for the
      generation of free radicals. Corona characteristics and decomposition of toluene
      were investigated experimentally. In addition, the decomposition mechanism of
      toluene was explored in view of reaction rate. The experimental results showed
      that the humidity of additional gas has an important effect on corona
      characteristics and modes and stable streamer corona can be generated through
      optimizing flow rate and humidity of additional gas. Applied voltage,
      concentration of toluene, humidity of toluene and resident time are some
      important factors affecting decomposition efficiency. Under optimizing
      conditions, the decomposition efficiency of toluene can reach 80%. These results
      can give a conclusion that the corona radical shower technology is feasible and
      effective on the removal of toluene in the flue gas.

PMID- 15495953
TI  - Effect of carbon source and nitrate concentration on denitrifying phosphorus
      removal by DPB sludge.
AB  - Effect of added carbon source and nitrate concentration on the denitrifying
      phosphorus removal by DPB sludge was systematically studied using batch
      experiments, at the same time the variation of ORP was investigated. Results
      showed that the denitrifying and phosphorus uptake rate in anoxic phase increased
      with the high initial anaerobic carbon source addition. However once the initial
      COD concentration reached a certain level, which was in excess to the PHB
      saturation of poly-P bacteria, residual COD carried over to anoxic phase
      inhibited the subsequent denitrifying phosphorus uptake. Simultaneously,
      phosphate uptake continued until all nitrate was removed, following a slow
      endogenous release of phosphate. High nitrate concentration in anoxic phase
      increased the initial denitrifying phosphorus rate. Once the nitrate was
      exhausted, phosphate uptake changed to release. Moreover, the time of this
      turning point occurred later with the higher nitrate addition. On the other hand,
      through on-line monitoring the variation of the ORP with different initial COD
      concentration, it was found ORP could be used as a control parameter for
      phosphorus release, but it is impossible to utilize ORP for controlling the
      denitrificaion and anoxic phosphorus uptake operations.

PMID- 15495954
TI  - Determination of methyl tert-butyl ether (MTBE) in Chinese fuels by gas
      chromatography/mass spectrometry and gas chromatography/flame ionization
      detector.
AB  - A method was developed to determine the concentration of methyl tert-butyl
      ether(MTBE) in gasoline, diesel and heating oil by gas chromatography(GC) with
      mass spectrometry(GC-MS) or flame ionization detection (FID). The diluted
      gasoline was directly injected into the GC, and the complete separation of MTBE
      from co-eluting hydrocarbons was not required. GC/MS or GC/FID method can be used
      to analyze MTBE in different concentration range and have good consistency.

PMID- 15495955
TI  - Kinetics study on catalytic wet air oxidation of phenol by several metal oxide
      catalysts.
AB  - Four metal oxide catalysts composed of copper (Cu), stannum(Sn), copper-stannum
      (Cu-Sn) and copper-cerium(Cu-Ce) respectively were prepared by the co
      impregnation method, and gamma-alumina (gamma-Al2O3) is selected as support. A
      first-order kinetics model was established to study the catalytic wet air
      oxidation of phenol at different temperature when these catalysts were used. The
      model simulations are good agreement with present experimental data. Results
      showed that the reaction rate constants can be significantly increased when
      catalysts were used, and the catalyst of 6% Cu--10% Ce/gamma-Al2O3 showed the
      best catalytic activity. This is consistent with the result of catalytic wet air
      oxidation of phenol and the COD removal can be arrived at 98.2% at temperature
      210 degrees C, oxygen partial pressure 3 MPa and reaction time 30 min. The
      activation energies of each reaction with different catalysts are nearly equal,
      which is found to beabout 42 kJ/mol and the reaction in this study is proved to
      be kinetics control.

PMID- 15495956
TI  - Incorporating sorption/desorption of organic pollutants into river water quality
      model.
AB  - Preliminary research was conducted about how to incorporate sorption/desorption
      of organic pollutants with suspended solids and sediments into single-chemical
      and one-dimensional water quality model of Jinghang Canal. Sedimentation
      resuspension coefficient k3 was deduced; characteristics of organic pollutants,
      concentrations and components of suspended solids/sediments and hydrological and
      hydraulic conditions were integrated into k3 and further into river water quality
      model; impact of sorption/desorption of organic pollutants with suspended solids
      and sediments on prediction function of the model was discussed. Results
      demonstrated that this impact is pronounced for organic pollutants with
      relatively large Koc and Kow, especially when they are also conservative and f.o
      of river suspended solids/sediments is high, and that incorporation of
      sorption/desorption of organic pollutants into river water quality model can
      improve its prediction accuracy.

PMID- 15495957
TI  - Sorption of biodegradation end products of nonylphenol polyethoxylates onto
      activated sludge.
AB  - Nonylphenol(NP), nonylphenoxy acetic acid (NP1EC), nonylphenol monoethoxy acetic
      acid (NP2EC), nonylphenol monoethoxylate (NP1EO) and nonylphenol diethoxylate
      (NP2EO) are biodegradation end products (BEPs) of nonionic surfactant
      nonylphenolpolyethoxylates (NPnEO). In this research, sorption of these compounds
      onto model activated sludge was characterized. Sorption equilibrium experiments
      showed that NP, NP1EO and NP2EO reached equilibrium in about 12 h, while
      equilibrium of NP1EC and NP2EC were reached earlier, in about 4 h. In sorption
      isotherm experiments, obtained equilibrium data at 28 degrees C fitted well to
      Freundlich sorption model for all investigated compounds. For NP1EC, in addition
      to Freundlich, equilibrium data also fitted well to Langmuir model. Linear
      sorption model was also tried, and equilibrium data of all NP, NP1EO, NP2EO and
      NP2EC except NP1EC fitted well to this model. Calculated Freundlich coefficient
      (K(F)) and linear sorption coefficient (K(D)) showed that sorption capacity of
      the investigated compounds were in order NP > NP2EO > NP1EO > NP1EC approximately
      NP2EC. For NP, NP1EO and NP2EO, high values of calculated K(F) and K(D) indicated
      an easy uptake of these compounds from aqueous phase onto activated sludge.
      Whereas, NP1EC and NP2EC with low values of K(F) and K(D) absorbed weakly to
      activated sludge and tended to preferably remain in aqueous phase.

PMID- 15495958
TI  - Characterization of fine organic particulate matter from Chinese cooking.
AB  - PM2.5 samples were collected by a three-stage cascade impactor at two kinds of
      Chinese restaurants to characterize fine organic particulate matter from Chinese
      cooking sources. Major individual organic compounds have been quantified by
      GC/MS, including series of alkanes, n-alkanoic acids, n-alkanals, alkan-2-ones
      and PAHs. Alkanes and ketones make up a significant fraction of particle-phase
      organic compounds, ranging from C11 to C26, and C9 to C19, respectively. In
      addition, other organic compound classes have been identified, such as alkanols,
      esters, furans, lactones, amides, and nitriles. The mass concentrations of fine
      particles, alkanes, n-alkanoic acids and PAHs in air emitted from the Uigur style
      cooking are hundreds times higher than ambient PM2.5 in Beijing.

PMID- 15495959
TI  - A new approach of drawing airport noise contours on computer based on Surfer.
AB  - Noise contours are used to describe the extent of airport noise pollution and to
      plan land use around airports. The L(WECPN) (weighted equivalent continuous
      perceive noise level) recommended by ICAO(International Civil Aviation
      Organization) is adopted as airport noise rating parameter in this paper. With
      the help of various mathematical models in the software Surfer, noise contours
      can be drawn automatically by the completed program in Visual C++ Code.
      Corrections for thrust, velocity, atmospheric temperature, humidity and lateral
      ground attenuation are also considered in the new method, which can improve the
      efficiency of drawing contours. An example of its use for drawing noise contours
      of an airport in Zhejiang Province of China is proposed and the predictions and
      the measurements show agreements well.

PMID- 15495960
TI  - Diversity surveys of soil bacterial community by cultivation--based methods and
      molecular fingerprinting techniques.
AB  - By combining the cultivation methods with molecular fingerprinting techniques,
      the diversity surveys of soil bacterial community in 13 areas of China were
      carried out. The cultivable heterotrophic diversity was investigated by colony
      morphology on solid LB medium. Genetic diversity was measured as bands on
      denaturing gradient gel electrophoresis(DGGE) by the extraction and purification
      of the total soil DNA, and amplification of bacterial 16S rDNA fragments by
      polymerase chain reaction (PCR). The Shannon-Wiener indices of diversity (H),
      richness (S) and evenness (E(H)) were employed to estimate the diversity of soil
      bacterial community. The results showed that there was an obvious diversification
      existed in soil from the different areas. However, the genetic diversity
      estimated by PCR-DGGE can provide more comprehensive information on bacterial
      community than the cultivation-based methods. Therefore, it is suggested to
      combine the traditional methods with genetic fingerprinting techniques to survey
      and estimate soil bacterial diversity.

PMID- 15495961
TI  - Coagulation of micro-polluted Pearl River water with IPF-PACls.
AB  - Water samples collected from early March 2001 to the end of April 2002 at the
      branch of Pearl River around the Guangzhou City were analyzed for its micro
      polluted characteristics. The coagulation behavior of polyaluminum chlorides
      (PACls) was then examined focusing on the effect of primary water quality and
      speciation distribution. The results showed that PACls exhibit better coagulation
      efficiency than alum in accordance with the different speciation. The turbidity
      removal property of PACls is evidently better than alum at low dosage. While in
      neutral zone (about 6.5-7.5), the turbidity removal of PACls decreases owing to
      the restabilization of particles at higher dosage. The organic matters in raw
      water exhibit marked influence on coagulation. In acidic zone, organic matters
      complex with polymer species and promote the formation of flocs. With an increase
      in pH, the complexation of organics with polymer species gradually decreases, and
      the removal of organics mainly depends on adsorption. The effect is evidently
      improved with the raise of B value.

PMID- 15495963
TI  - Characteristics of Cd uptake and accumulation in two Cd accumulator oilseed rape
      species.
AB  - Two pot experiments were conducted under greenhouse conditions to investigate the
      characteristics of Cd uptake and accumulation by two Cd accumulator oilseed rape
      varieties and one Indian mustard grown on a loamy soil that had been artificially
      contaminated by different amounts of CdSO4 (0, 20, 40, 60, 80, 100 mg/kg soil).
      The relationship between shoot Cd uptake of the two oilseed rape cultivars and
      the soil Cd concentrations could be simulated via quadratic equations. The curve
      showed that maximum shoot Cd uptake of Indian mustard was 314.7 microg/pot at
      soil Cd concentration of 87.8 mg/kg, while maximum uptake of the variety Xikou
      Huazi was 543.3 microg/pot at soil Cd concentration of 69.1 mg/kg and that of the
      variety Zhongyou Za-1hao was 576.7 microg/pot at soil Cd concentration of 84.0
      mg/kg, suggesting that shoot Cd uptake ability of the two Cd accumulator oilseed
      rapes was significantly higher than that of the Indian mustard. Xikou Huazi had
      higher phytoremediation potential for Cd contaminated soil. Shoot Cd accumulation
      ability of the two Cd accumulator oilseed rapes was correspond and Cd was easier
      translocated to the shoot than hyperaccumulator Indian mustard as comparation
      plant. Shoot Cd distribution pattern showed consistent and significant reduction
      from older leaves to younger ones of two oilseed rapes and Indian mustard. Cd
      uptake by oilseed rapes in growth prophase was higher than that of growth
      anaphase.

PMID- 15495962
TI  - Characterization and phylogenetic analysis of a phenanthrene-degrading strain
      isolated from oil-contaminated soil.
AB  - Bacterium strain EVA17 was isolated from an oil-contaminated soil, and identified
      as Sphingomonas sp. based on analysis of 16S rDNA sequence, cellular fatty acid
      composition and physiological-chemical tests. The salicylate hydroxylase and
      catechol 2, 3-dioxygenase (C230) were detected in cell-free lysates, suggesting a
      pathway for phenanthrene catabolism via salicylate and catechol. Alignment showed
      that both of the C230 and GST genes of the strain EVA17 had high similarity with
      homologues of strains from genus Sphingomonas. The phylogenetic analysis based on
      16S rDNA and C230 gene sequence indicated that EVA17 should be classified into
      genus Sphingomonas, although the two phylogenetic trees were slightly different
      from each other. The results of coamplification and sequence determination
      indicated that GST gene should be located upstream of the C230 gene.

PMID- 15495964
TI  - Overview of surface ozone variability in East Asia-North Pacific region during
      IGAC/APARE (1994--1996).
AB  - Surface ozone (O3) was measured at Oki Island (Japan), Cheju Island (South
      Korea), Lanyu Island (Taiwan Province, China), Cape D'Aguilar (Hong Kong SAR) and
      Lin'an, Longfenshan, Waliguan (China mainland) during January 1994--December 1996
      as a component of IGAC/APARE (International Global Atmospheric Chemistry/East
      Asia-North Pacific Regional Experiment). This paper gave a joint discussion on
      the observational results at these stations over the study region. Investigations
      showed that the average of surface O3 mixing ratios at the seven sites are 47.9+/
      15.8, 48.1+/-17.9, 30.2+/-16.4, 31.6+/-17.5, 36.3+/-17.5, 34.8+/-11.5 and 48.2+/
      9.5 ppbv, respectively. Significant diurnal variations of surface O3 have been
      observed at Oki, Cheju, D'Aguilar, Lin'an and Longfenshan. Their annual averaged
      diurnal differences range from 8 to 23 ppbv and differ in each season. Surface O3
      at Lanyu and Waliguan do not show strong diurnal variability. Seasonal cycles of
      surface O3 showed difference at the temperate and the subtropical remote sites.
      Oki has a summer minimum-spring maximum, while Lanyu has a summer minimum-autumn
      maximum. The suburban sites at D'Aguilar and Lin'an report high-level O3 in
      autumn and low level O3 in summer. Surface O3 remains-high in autumn and low in
      winter at the rural site Longfenshan. For the global background station Waliguan,
      surface O3 exhibits a broad spring-summer maximum and autumn-winter minimum. The
      backward air trajectories to these sites have shown different pathways of long
      range transport of air pollution from East Asia Continent to North Pacific Ocean.
      Surface O3 was found to be strongly and positively correlated with CO at Oki and
      Lanyu, especially in spring and autumn, reflecting the substantial photochemical
      buildup of O3 on a regional scale. It is believed that the regional sources of
      pollution in East Asia have enhanced the average surface O3 concentrations in the
      background atmosphere of North Pacific.

PMID- 15495965
TI  - Adopting an ecological view of metropolitan landscape: the case of "three
      circles" system for ecological construction and restoration in Beijing area.
AB  - Ecological construction and restoration for sustainable development are now a
      driving paradigm. It is increasingly recognized that ecological principles,
      especially landscape ecology theory, are not only necessary but also essential to
      maintain the long-term sustainability worldwide. Key landscape ecology principles
      element, structure and process, dynamics, heterogeneity, hierarchies,
      connectivity, place and time were reviewed, and use Beijing area as a case study
      to illustrate how these principles might be applied to ecological construction
      and restoration, to eventually achieve sustainability. An example to more
      effectively incorporate the ecological principles in sustainable planning in
      China was presented.

PMID- 15495966
TI  - Control of diffuse P-pollutants by multiple buffer/detention structures by Yuqiao
      Reservoir, North China.
AB  - A case study on the transport process of agricultural diffuse P-pollutants was
      conducted in an experimental watershed locating in the north bank of Yuqiao
      Reservoir during 2001 and 2002. It was found that diversified artificial and
      natural buffer/detention landscape structures distributing along the ephemeral
      stream channel in this watershed played an important role of pollutants removal
      on downstream water quality, especially they have control effect on the diffuse P
      pollutants transport process. Surface flow velocity was reduced sharply after
      passing through these structures. During continuous runoff events, the removal
      rate of TSS, TP, TDP, DRP by the whole system were 66.7%, 60.7%, 48.4%, and
      43.3%, respectively. During discontinuous runoff events, removal rate of
      pollutants by the whole system was higher due to there was no or little surface
      water and pollutants exported from the watershed, of which removal rate of
      pollutants all exceeded 99% . The statistical analysis results of runoff events
      (n = 8) indicated that dry pond was the steadiest structure for controlling
      diffuse P-pollutants export.

PMID- 15495967
TI  - Catalytic dechlorination of o-chlorophenol by nanoscale Pd/Fe.
AB  - Transformation of chlorophenols by nanoscale bimetallic particles represents one
      of the latest innovative technologies for environmental remediation. Nanoscale
      Pd/Fe bimetallic particles were synthesized in the laboratory for treatment of o
      chlorophenol. Most of the nanoscale particles are in the size range of 20-100 nm.
      BET specific surface area of the nanoscale Pd/Fe particles is 12.4 m2/g. In
      comparison, a commercially available Fe powder( < 100 mesh) has a specific
      surface area of just 0.49 m2/g. Batch experiments demonstrated that the nanoscale
      Pd/Fe bimetallic particles can effectively dechlorinate o-chlorophenol.
      Dechlorination efficiency is affected by the mass fraction of Pd in the bimetal,
      nanoscale Pd/Fe mass concentration and mixing intensity.

PMID- 15495968
TI  - Characteristics of aerobic granules grown on glucose a sequential batch shaking
      reactor.
AB  - Aerobic heterotrophic granular sludge was cultivated in a sequencing batch
      shaking reactor (SBSR) in which a synthetic wastewater containing glucose as
      carbon source was fed. The characteristics of the aerobic granules were
      investigated. Compared with the conventional activated sludge flocs, the aerobic
      granules exhibit excellent physical characteristics in terms of settleability,
      size, shape, biomass density, and physical strength. Scanning electron
      micrographs revealed that in mature granules little filamentous bacteria could be
      found, rod-shaped and coccoid bacteria were the dominant microorganisms.

PMID- 15495969
TI  - Adsorption of zinc on manganite (gamma-MnOOH): particle concentration effect and
      adsorption reversibility.
AB  - The adsorption and desorption processes of Zn(II) on gamma-MnOOH as a function of
      particle concentrations (Cp) were studied. An obvious Cp effect was observed in
      this adsorption system. The degree of adsorption hysteresis increased greatly
      with the increasing of Cp, indicating that the extent of the real metastable
      equilibrium states deviating from the ideal equilibrium state was enhanced with
      the increasing of Cp. The Cp-reversibility relationship confirmed the metastable
      equilibrium adsorption (MEA) inequality (Pan, 1998a), which was the core
      formulation of the MEA theory. Because the MEA inequality was based on the basic
      hypothesis of MEA theory that adsorption density [see symbol in text] is not a
      state variable, the Cp-reversibility relationship gave indirect evidence to the
      basic hypothesis of MEA theory.

PMID- 15495970
TI  - Impact of some chlorinated pesticides on the haematology of the fish Cyprinus
      carpio and Puntius ticto.
AB  - The effects of pesticides on blood characteristics and histological changes in
      erythrocytes of the fish species Cyprinus carpio and Puntius ticto were studied.
      The fishes were exposed to sub lethal concentrations of different chlorinated
      pesticides namely aldrin, dieldrin, DDT, BHC and chlordane for 10, 20 and 30 d in
      continuous flow-through test. The LC50 values were calculated based on acute
      toxicity tests and the sublethal doses were arrived at for chronic bioassay
      studies. Results showed an increase in haemoglobin content of both Cyprinus
      carpio and Puntius ticto in case of aldrin and dieldrin. Haemoglobin content
      reduced from an initial 13 g/100 ml to 8.07 and 10.15 g/100 ml in case of
      Cyprinus at the end of ten days exposure to aldrin and dieldrin respectively, and
      gradually increased to 8.7 g/100 ml and 10.15 g/100 ml after 20 d of exposure.
      The haemoglobin content after 30 d exposure to aldrin and dieldrin was 10.15
      g/100 ml and 11.6 g/100 ml respectively. In case of Puntius ticto, the
      haemoglobin content in control fishes recorded was 12.8 g/100 ml while in case of
      fish exposed to aldrin, the haemoglobin content reduced initially on ten days
      exposure to 10.15 g/100 ml and increased to 11.6 g/100 ml and 13.0 g/100 ml
      during twenty days and thirty days exposure respectively. This trend was also
      observed with dieldrin in both the fishes studied. Red blood cells were also
      counted in case of all the pesticides and exposure periods with respect to
      Cyprinus carpio and Puntius ticto. Irrespective of the species and pesticide, the
      RBC counts uniformly showed decreasing trend with the increase in exposure
      period, while packed cell volume, PCV(%) showed increasing trend with respect to
      increase in exposure period in case of aldrin and dieldrin in both the fishes.
      But DDT, BHC and chlordane showed decreasing trend in PCV(%) values with
      increasing periods of exposure.

PMID- 15495971
TI  - Volatilization of heavy metals during incineration of municipal solid wastes.
AB  - Incineration experiments with MSW, which had been impregnated with heavy metals,
      were presented to obtain information on the volatilization behavior of the
      elements cadmium(Cd), lead (Pb), and zinc (Zn) under different conditions.
      Experiments were carried out in a bubbling fluid bed system connected to a
      customized inductively coupled plasma optical emission spectroscopy (ICP-OES) for
      analyzing metals in the flue gas. The results indicated that the combustion
      temperature, the gas atmosphere, and the chlorine content in the flue gas could
      affect the volatilization behavior of heavy metals. In the fluidized bed
      combustion, a large surface area was provided by the bed sand particles, and they
      may act as absorbents for the gaseous ash-forming compound. Comparer with the
      metals Cd and Pb, the vaporization of Zn was low. The formation of stable
      compounds such as ZnO x Al2O3 could greatly decrease the metals volatilization.
      The presence of chlorine would enhance the volatilization of heavy metals by
      increasing the formation of metal chlorides. However, when the oxygen content was
      high, the chlorinating reaction was kinetically hindered, which heavy metals
      release would be delayed.

PMID- 15495972
TI  - Immobilization study of biosorption of heavy metal ions onto activated sludge.
AB  - Activated sludge was immobilized into Ca-alginate beads via entrapment, and
      biosorption of three heavy metal ions, copper(II), zinc(II), and chromimum(II),
      from aqueous solution in the concentration range of 10-100 mg/L was studied by
      using both entrapped activated sludge and inactivated free biomass at pH < or =
      5. A biphasic metal adsorption pattern was observed in all immobilized biomass
      experiments. The biosorption of metal ions by the biosorbents increased with the
      initial concentration increased in the medium. The adsorption rate of immobilized
      pretreated activated sludge(PAS) was much lower than that of free PAS due to the
      increase in mass transfer resistance resulting from the polymeric matrix.
      Biosorption equilibrium of beads was established in about 20 h and the adsorbed
      heavy metal ions did not change further with time. No significant effect of
      temperature was observed in the test for free biomass while immobilized PAS
      appeared to be strong temperature dependent in the test range of 10 and 40
      degrees C. Besides, the content of activated sludge in the calcium alginate bead
      has an influence on the uptake of heavy metals. The sorption equilibrium was well
      modeled by Langmuir isotherm, implying monomolecular adsorption mechanism.
      Carboxyl group in cell wall played an important role in surface adsorption of
      heavy metal ions on PAS.

PMID- 15495973
TI  - A distributed non-point source pollution model: calibration and validation in the
      Yellow River Basin.
AB  - The applicability of a non-point source pollution model--SWAT(soil and water
      assessment tools) in a large river basin with high sediment runoff modulus(770
      t/km2 in the Yellow River) was examined. The basic database, which includes DEM,
      soil and landuse map, weather data, and land management data, was established for
      the study area using GIS. A two-stage "Brute Force" optimization method was used
      to calibrate the parameters with the observed monthly flow and sediment data from
      1992 to 1997. In the process of calibration automated digital filter technique
      was used to separate direct runoff and base flow. The direct runoff was firstly
      calibrated, and the base flow, then the total runoff was matched. The sediment
      yield was calibrated to match well. Keeping input parameters set during the
      calibration process unchanged, the model was validated with 1998--1999's observed
      monthly flow and sediment. The evaluation coefficients for simulated and observed
      flow and sediment showed that SWAT was successfully applied in the study area:
      relative error was within 20%, coefficient of determination and Nash-Suttcliffe
      simulation efficiency were all equal to or above 0.70 during calibration and
      validation period.

PMID- 15495974
TI  - Influence of osmotic distillation on membrane absorption for the treatment of
      high strength ammonia wastewater.
AB  - Osmotic distillation (OD) was found to be a coupled process in membrane
      absorption (MA) for the treatment of high strength ammonia wastewater. As a
      result, ammonia could not be concentrated in absorption solution(AS) as expected.
      The inhibition of the coupled OD in MA process was investigated as well as
      various factors affecting the inhibition. The results indicated that the coupled
      OD can be effectively inhibited by heating concentrated solution and cooling
      dilute solution. It was also found that experimental minimum inhibition
      temperature difference(MITD) between concentrated and dilute solutions was
      different when using polyvinylidene fluoride(PVDF) and polypropylene(PP)
      membranes respectively, which could be ascribed to material properties, such as
      OD and membrane distillation (MD) coefficients of the membranes. Experimental
      MITDs were found to be higher than theoretical MITDs which were calculated using
      a simplified method.

PMID- 15495975
TI  - Biological removal of air loaded with a hydrogen sulfide and ammonia mixture.
AB  - The nuisance impact of air pollutant emissions from wastewater pumping stations
      is a major issue of concern to China. Hydrogen sulfide and ammonia are commonly
      the primary odor and are important targets for removal. An alternative control
      technology, biofiltration, was studied. The aim of this study is to investigate
      the potential of unit systems packed with compost in terms of ammonia and
      hydrogen sulfide emissions treatment, and to establish optimal operating
      conditions for a full-scale conceptual design. The laboratory scale biofilter
      packed with compost was continuously supplied with hydrogen sulfide and ammonia
      gas mixtures. A volumetric load of less than 150 gH2S/(m3 x d) and 230 gNH3/(m3 x
      d) was applied for about fifteen weeks. Hydrogen sulfide and ammonia elimination
      occurred in the biofilter simultaneously. The removal efficiency, removal
      capacity and removal kinetics in the biofilter were studied. The hydrogen sulfide
      removal efficiency reached was very high above 99%, and ammonia removal
      efficiency was about 80%. Hydrogen sulfide was oxidized into sulphate. The
      ammonia oxidation products were nitrite and nitrate. Ammonia in the biofilter was
      mainly removed by adsorption onto the carrier material and by absorption into the
      water fraction of the carrier material. High percentages of hydrogen sulfide or
      ammonia were oxidized in the first section of the column. Through kinetics
      analysis, the presence of ammonia did not hinder the hydrogen sulfide removal.
      According to the relationship between pressure drop and gas velocity for the
      biofilter and Reynolds number, non-Darcy flow can be assumed to represent the
      flow in the medium.

PMID- 15495976
TI  - Microbiological indication of municipal solid waste landfill non-stabilization.
AB  - Accidental collapse resulted from unstable factors is an important technological
      problem to be solved in sanitary landfill. Microbiological degradation of organic
      matters in landfilled solid waste are an important unstable factor. A landfill
      reactor was thus manufactured and installed to examine quantitative and
      population dynamics of microorganisms during degradation of landfilled solid
      waste. It was showed that unstable landfill can be reflected and indicated by
      microbiological features such as rapidly decreased growth amount of
      microorganisms, no detection of fungi and actinomyces, and changing the dominant
      population into methanogenic bacteria and Acinotobacter.

PMID- 15495977
TI  - Responses of chlorophyll fluorescence and nitrogen level of Leymus chinensis
      seedling to changes of soil moisture and temperature.
AB  - Controlled experiment of Leymus chinensis seedlings grown in the environmental
      growth chambers at 3 soil moisture levels and 3 temperature levels was conducted
      in order to improve the understanding how leaf photosynthetic parameters will
      respond to climatic change. The results indicated that soil drought and high
      temperature decreased the photochemical efficiency of photosystem (Fv/Fm), the
      overall photochemical quantum yield of PSII(yield), the coefficient of
      photochemical fluorescence quenching(qP), but increased the coefficient of non
      photochemical fluorescence quenching(qN). Severe soil drought would decrease
      Fv/Fm and yield by 3.12% and 37.04% under 26 degrees C condition, respectively,
      and 6.60% and 73.33% under 32 degrees C condition, respectively, suggesting that
      higher temperature may enhance the negative effects of soil drought. All the soil
      drought treatments resulted in the decline in leaf nitrogen content. There was no
      significant effect of temperature on leaf nitrogen level, but higher temperature
      significantly reduced the root nitrogen content and the ratio of root nitrogen to
      leaf nitrogen, indicating the different strategies of adaptation to soil drought
      and temperature. It was also implied that higher temperature would enhance the
      effect of soil drought on leaf photosynthetic capacity, decrease the adaptability
      of Leymus chinensis to drought.

PMID- 15495978
TI  - Responses of Sesbania rostrata and S. cannabina to Pb, Zn, Cu and Cd toxicities.
AB  - Responses of Sesbania rostrata and S. cannabina to Pb, Zn, Cu and Cd toxicities
      were assessed by a seed-suspending seedbed(SSS) approach. The results showed that
      the SSS approach was suitable for testing the tolerance of a plant to the stress
      of toxic metals. The endpoints include seed germination success, straightened
      radicle and hypocotyl of the seedlings from the seeds. The measurements could be
      done easily and accurately. It was found that the elongation of radicle was the
      most sensitive indicator to the stress of heavy metals among the endpoints. When
      exposure to lower or medium concentrations of Pb, Zn, and Cd, the development of
      the lateral roots were favorable. Species of S. rostrata was more tolerant than
      S. cannabina to the heavy metals, especially to Zn and Cd. The ED50 of Pb, Zn, Cu
      and Cd were 32.90, 5.32, 4.40 and 12.00 microg/ml for S. rostrata, respectively,
      and they were 30.11, 2.87, 4.05 and 4.94 microg/ml respectively for S. cannabina.

PMID- 15495979
TI  - Experimental study on the simultaneous desulfurization and denitrification by
      duct injection.
AB  - The highly active absorbent with oxidization based on fly ash, lime and additive
      was prepared. Experiments of simultaneous desulfurization and denitrification
      were carried out using fixture bed and duct injection. The influencial factors
      for the absorptive capacity of the absorbent were studied. The absorptive
      capacities of 120.7 mg for SO2 and 43.7 mg for NOx were achieved at a Ca/(S + N)
      molar ratio 1.2, respectively, corresponding removal efficiencies of 87% and 76%,
      while spent absorbent appeared in the form of dry powder. The optimal temperature
      and humidity of flue gas treated with this process were shown to be approximately
      50 degrees C, and 5% respectively. The mechanism of removal for SO2 and NOx was
      investigated. In comparison with traditional dry FGD, this process appears to
      have lower cost, less complicated configuration and simpler disposal of used
      absorbent. The valuable references can be provided for industrial application by
      this process. The foreground of application will be vast in China and in the
      world.

PMID- 15495980
TI  - Clomazone dissipation, adsorption and translocation in four paddy topsoils.
AB  - Laboratory experiments about the dissipation, adsorption and translocation in
      four paddy topsoils were conducted in this paper. From the results it can be
      concluded as follows: the dissipation rate of clomazone differed greatly in
      different paddy soil derived from different parent materials. The half-lives for
      clomazone degradation in paddy soils ranged from 5.7 to 22.0 d. The order of
      clomazone dissipation rate was reddish yellow paddy soil > alluvial sandy paddy
      soil > yellow clayey paddy soil > purple sandy paddy soil. Clomazone sorption
      quantity was significantly correlated with organic carbon (R2 = 0.62) and clay
      content(R2 = 0.67) in the tested paddy soils. Positive correlation was found
      between apparent Kd value and cation exchange content(CEC). The consequences for
      the adsorption of different soils were purple sandy paddy soil > yellow clayey
      paddy soil > reddish yellow paddy soil > alluvial sandy paddy soil. Under the
      simulated rainfall of 200 mm through four different unsaturated soil lysimeters
      over 24 h, clomazone was readily to be leached into lower surface soil and there
      was about 2.6%--4.2% of applied clomazone leached out of 20 cm cultivated soil
      layer. Translocation experiments showed that the order of clomazone leaching
      ability was: alluvial sandy paddy soil > reddish yellow paddy soil > yellow
      clayey paddy soil > purple sandy paddy soil. Simple regression results manifested
      that factors like CEC, organic carbon, clay, and adsorption rate constant had
      been negatively correlated with the percentage of clomazone loss from soil
      lysimeters.

PMID- 15495981
TI  - Effect of pyrolysis temperature and hold time on the characteristic parameters of
      adsorbent derived from sewage sludge.
AB  - According to the Doehlert's matrix method, the adsorbent derived from sewage
      sludge was prepared through chemical activation under controlling the pyrolysis
      temperature and hold time. The characteristic parameters including the total
      yield, adsorption of methylene blue, adsorption of iodine, BET surface area,
      micro-pore volume are 35%--49%, 16.5--38 mg/g, 285--362 mg/g, 185--359 m2/g, and
      0.112--0.224 m3/g, respectively. According to the experimental data, the multi
      linear regression method was adopted to fit the relations between the
      characteristic parameters and influential factors. At final, through optimization
      method, the optimal adsorbent is obtained when using 62 min as hold time and
      1105K as pyrolysis temperature. Under the conditions, the adsorbent was produced
      and compared the characteristic parameters with model forecast value, the
      coherence is satisfied.

PMID- 15495982
TI  - Determination of hydroxyl radicals with salicylic acid in aqueous nitrate and
      nitrite solutions.
AB  - The qualitative and quantitative analyses of reactive oxygen species are
      essential to determine their steady-state concentration and related reaction
      mechanisms in environmental aquatic systems. In this study, salicylic acid was
      employed as an innovative molecular probe of hydroxyl radical(OH) generated in
      aqueous nitrate and nitrite solutions through photochemical reactions. Kinetic
      studies showed that the steady-state concentrations of OH in aqueous NO3- (10
      mmol/L, pH = 5) and NO2- (10 mmol/L, pH = 5) solutions under ultraviolet
      irradiation were at a same magnitude, 10(-15) mol/L. Apparent quantum yields of
      OH at 313 nm were measured as 0.011 and 0.07 for NO3- and NO2- respectively, all
      comparable to the results of previous studies.

PMID- 15495983
TI  - Straw bio-degradation by acidogenic bacteria and composite fungi.
AB  - A composite microbial system, including a strain of Candida tropicalis (W3), a
      strain of Lactobacillus plantarm(WY3) and three strains of basidiomycete pL104,
      pL113 and C33, was chosen to degrade corn straw. The final pH was acid owing to
      the inoculation of acidogenic bacteria, and under this condition the composite
      fungi system could produce complex enzyme to destroy the compact structure of
      corn straw. The experimental results showed that the biomass of composite fungi
      could reach up to maximum when the pH value was 4.5. Through the bio-degradation
      by combining acidogenic bacteria with the composite fungi system, the cellulose,
      hemi-cellulose and lignin degradation rates of corn straw powder were 26.36%,
      43.30% and 26.96%, respectively. And the gross crude protein content increased
      60.41%. This study provided the evidence for the feasibility of developing a
      composite microbial system with high capability of degrading straw
      lignocelluloses in order to make reasonable use of straw resource and protect
      rural eco-environment.

PMID- 15495984
TI  - A method to extract algae toxin of microcystin-LR.
AB  - A simple and low-cost method to obtain cyanobacterial toxin microcystin-LR (MC
      LR) was developed. A new strain of Microcystis aeruginosa, named DC-1, producing
      microcystin-LR but not microcystin-RR, was separated from the field blooming
      algae samples of Dianchi Lake, in southwest of China. Following three times'
      freeze and thaw treatment, the cultivated DC-1 cells were extracted with 40%
      methanol in water. The extract was centrifuged and the supernatant applied to a
      Hydrophilic-Lipophilic Balance (HLB) SPE cartridge. Eluted impurities with a
      certain gradient from 30% to 50% methanol in water, MC-LR was finally eluted from
      the HLB cartridge with 60% methanol in water, and samples containing 3.85% to
      14.8% of MC-LR were obtained. These MC-LR samples may be used in adsorption and
      biodegradation experiments instead of using expensive standard reagents.

PMID- 15495985
TI  - Spatial and temporal variability of agricultural pollutants in an agricultural
      headwater stream within a multipond system, southeastern China.
AB  - The spatial and temporal variability of nutrients and suspended solids were
      investigated for two years in a 1.8 km agricultural headwater stream, located by
      Chaohu Lake, southeastern China. The stream form was greatly modified by human
      activities into channelized, pond and estuary shapes. The stream could be divided
      into 4 channelized reaches(1.3 km), a pond reach(0.15 km) and 3 estuary
      reaches(0.36 km). It was found that nutrients and TSS concentrations in the
      stream showed temporal variability, and higher concentrations occurred in months
      with high precipitation and intensive agricultural activities. And, retention of
      total nitrogen (TN), nitrate (NO(3-)-N), ammonium(NH4+-N) and total suspended
      solids (TSS) predominantly occurred in the pond reach and estuary reaches with
      larger width and low current velocity. Pollutants retained in these reaches
      accounted for more than 50% of those retained in whole stream. The retention
      mostly happened in the rain-runoff events and it was 7 to 27 times than that in
      base flow. The results showed that the channelized reach was the most important
      source for pollutants release under either runoff or base flow, and its release
      accounted for more than 90% of whole stream release. There was a high spatial
      variability of nutrients retention in different channelized reaches. The
      channelized reach directly discharging into the pond did always retain nutrients
      and TSS under base flow and runoff conditions, whereas the other channelized
      reaches performed differently in different hydrological conditions. The high
      spatial and temporal variability of nutrients and TSS in the stream indicated
      that anthropogenic disturbance of the agricultural headwater stream, such as
      channelization and excavation, would be expected to decrease the capacity of
      nutrients retention in the stream.

PMID- 15495986
TI  - [A 'blind' transfusion policy in patients with acute severe blood loss].
AB  - Three patients presented with acute, excessive bleeding: a 54-year-old man
      following trauma to the pelvis, a 34-year-old woman with postpartum blood loss
      and a 62-year-old man with a duodenal ulcer. Treatment consisted of surgery, the
      administration of blood products and haemostatic agents, in varying strategies.
      The men recovered but the woman died as a result of cardiac rhythm disorders. It
      is unclear to what extent blood products should be used in patients with acute,
      excessive blood loss. Also, haemostatic agents have already found a place in the
      treatment of these patients, but it is unclear whether they should be
      administered early, as prophylaxis, or later when all other treatments have
      failed. While official registration of the haemostatic agent recombinant
      activated factor VII for this indication is pending, it is important that
      treatment with rFVIIa be embedded in a structured protocol to prevent overuse of
      blood products and administration of this medication to patients who do not need
      it. Controlled clinical trials for validation should be carried out prior to the
      implementation of such a protocol.

PMID- 15495987
TI  - [Diagnostic and pharmaco-therapeutic options in acute severe blood loss].
AB  - In patients with excessive blood loss, coagulation is compromised by hypothermia,
      metabolic acidosis due to impaired tissue perfusion, loss of coagulation factors
      and platelets while their consumption is increased, and by massive infusion with
      plasma expanders. Currently available laboratory tests are insufficiently
      reliable and too time-consuming to enable the evaluation of the effect of
      pharmaco-therapeutic interventions during severe blood loss. Several haemostatic
      drugs appear to be effective in the treatment of blood loss after elective
      surgery, but have been insufficiently investigated in patients with severe
      bleeding. A rational transfusion policy entailing the use of sufficient amounts
      of plasma is necessary in the treatment of patients with severe bleeding.

PMID- 15495988
TI  - [Analogs of glucagon-like peptide-1 (GLP-1): an old concept as a new treatment of
      patients with diabetes mellitus type 2].
AB  - Upon ingestion of food, the incretin hormones glucagon-like peptide-1 (GLP-1) and
      glucose-dependent insulinotropic polypeptide (GIP) are synthesised and secreted
      by specialised gut cells. GLP-1 is also produced in the pancreatic islets and the
      central nervous system. Both incretins bind to specific G-protein-coupled
      receptors that are distributed throughout the body. Incretins potentiate meal
      induced insulin production and secretion by the beta-cells and lower the blood
      glucose level in the presence of hyperglycaemia. GLP-1 and GIP stimulate beta
      cell proliferation and differentiation, whereas GLP-1 only inhibits gastric
      emptying and glucagon secretion, reduces food intake and improves insulin
      sensitivity. Insulin-resistant and type-2 diabetic patients have an impaired
      incretin response to meal ingestion. However, the insulinotropic action of
      exogenous GLP-1, but not that of GIP, is preserved in these subjects. After
      parenteral administration, GLP-1 has an extremely short duration of action
      because it is rapidly degraded by the ubiquitous enzyme dipeptidyl peptidase IV
      (DPPIV). To prolong GLP-1 bioactivity, DPPIV-resistant GLP-1 analogues, DPPIV
      inhibitors and exenatide, a long-acting synthetic GLP-1 receptor agonist derived
      from the Gila monster hormone exendin-4, have been developed. Enhancement of
      incretin action seems a rational and promising option for the treatment of type-2
      diabetes.

PMID- 15495989
TI  - [Diagnostic image (208). A women with intermittant ileus].
AB  - A 87-year-old woman presenting with nausea, vomiting and lack of defaecation had
      a palpable mass in the left upper abdomen due to an intussusception of the
      terminal ileum into the transverse colon caused by a coecal adenocarcinoma.

PMID- 15495990
TI  - [From gene to disease; familial hemiplegic migraine as a result of mutations in a
      sodium-potassium pump gene].
AB  - Familial hemiplegic migraine (FHM) is a rare, autosomal dominant subtype of
      migraine, associated in half of the families with mutations in the CACNA1A gene
      located on chromosome 19p13, which encodes the Cav2.1-subunit of brain-specific
      P/Q-type calcium channels. Recently, mutations in a second gene, ATP1A2 on
      chromosome 1q23, which encodes a sodium-potassium exchange pump subunit, have
      been identified. The first functional studies indicate that A TP1A2 FHM mutations
      result in a loss of function of the pump, leading to an increase in extracellular
      potassium. This is known to evoke cortical spreading depression, the underlying
      mechanism of migraine aura.

PMID- 15495991
TI  - [Hyponatraemia during the use of selective serotonin re-uptake inhibitors
      (SSRIs): reports from 1992-2002].
AB  - OBJECTIVE: To describe the reports of serotonin re-uptake inhibitor (SSRI)
      induced hyponatraemia that were sent to The Netherlands Pharmacovigilance Centre
      Lareb and the Inspectorate for Health Care. DESIGN: Descriptive study. METHOD:
      Reports of SSRI-induced hyponatraemia received by Lareb and the Inspectorate for
      Health Care during the period 1 January 1992 to 1 July 2002 were described on the
      basis of symptoms, co-medication and comorbidity. RESULTS; A total of 42 cases
      were reported, 38 (90%) of which concerned women and 21 (50%) of which concerned
      the concomitant use of SSRIs and diuretics. The mean age was 74 years (range: 30
      91). The mean serum sodium concentration was 115 mmol/l (range: 97-132). The most
      important symptoms were reduced consciousness, confusion, falls, nausea and
      vomiting. 3 patients (7%) died in the period of the reported adverse drug
      reaction and 27 patients (64%) were hospitalised, of which 4 (10%) to the
      intensive care unit. CONCLUSION: These reports of suspected SSRI-induced
      hyponatraemia were attended with significant morbidity and substantial mortality.
      The considerable morbidity and substantial mortality in combination with the
      increasing use of SSRIs necessitates a clarification of the actual incidence and
      severity of SSRI-induced hyponatraemia.

PMID- 15495992
TI  - [Trial therapy with proton pump inhibitors is not a suitable test for
      gastroesophageal reflux disease; a meta-analysis of the diagnostic test
      characteristics].
AB  - OBJECTIVE: To determine the value of successful trial therapy with proton-pump
      inhibitors (PPIs) as a diagnostic test for gastro-oesophageal reflux disease
      (GERD). DESIGN: Systematic review and meta-analysis. METHOD: Studies were
      included in which the clinical response to a short course (1-4 weeks) of PPI
      therapy could be related to abnormal results of 24-hr pH monitoring, gastroscopy,
      and/or diagnostic questionnaires. The sensitivity and specificity of the trial
      therapy were calculated. The ROC method was used to summarize the test
      characteristics across studies. RESULTS: With 24-hr pH monitoring as the
      reference standard, the positive likelihood ratio of the diagnosis 'reflux
      disease' ranged from 1.63 to 1.87 and the combined estimates of sensitivity and
      specificity in the various studies were 0.78 (95% CI: 0.66-0.86) and 0.54 (0.44
      0.65), respectively. These values were lower with the other reference standards.
      CONCLUSION: Although there were insufficient data to determine the effect of
      varying dosages of PPIs and duration of therapy on the test characteristics,
      successful short-term treatment with PPIs in patients suspected of having GERD
      provides insufficient certainty as to the diagnosis.

PMID- 15495993
TI  - [A man from Surinam with haemorrhagic diarrhoea after long-standing
      schistosomiasis].
AB  - A 35-year-old man presented with a brief history of haemorrhagic diarrhoea. He
      had moved to The Netherlands 24 years before and had been in Surinam 12 years ago
      for the last time. Physical examination and routine laboratory tests revealed no
      abnormalities. Colonoscopy showed a striking congestion of the small blood
      vessels; histological examination of a sigmoid biopsy revealed Schistosoma eggs
      and microbiological investigation of the feces revealed ova of Schistosoma
      mansoni. The schistosomiasis was thus diagnosed more than 10 years after the last
      possible exposure to schistosomal cercariae. The patient was treated with a
      single dose of praziquantel.

PMID- 15495994
TI  - [Two newborns with both small-bowel atresia and cystic fibrosis].
AB  - Two newborn girls presented with congenital small-bowel atresia; in one case a
      high intestinal obstruction had been demonstrated by prenatal echography, while
      in the other case there were feeding problems and a failure to produce meconium.
      In both infants, the postoperative period was complicated by feeding problems,
      malabsorption and insufficient growth. Cystic fibrosis (CF) was then diagnosed in
      both patients. After modification of the diet, both showed rapid growth to a
      normal weight. The prevalence of CF in children with congenital small-bowel
      atresia is 6-13%, which is considerably higher than in a normal population. There
      is still no good explanation for this finding, but it is likely that CF
      contributes to the development of small-bowel atresia. In view of the high
      prevalence of CF in children with small-bowel atresia, children with congenital
      small-bowel atresia should be examined for CF.

PMID- 15495995
TI  - [Repeated suicide attempts: a need for continued care].

PMID- 15495996
TI  - [Important prognostic significance of a sentinel-node biopsy in patients with
      malignant melanoma].

PMID- 15495997
TI  - [Uterine hyperstimulation following cervix ripening with dinoprostone in a
      vaginal insert system].

PMID- 15495998
TI  - [Summary of the practice guideline 'Peripheral vascular disease' (first revision)
      from the Dutch College of General Practitioners].

PMID- 15495999
TI  - [Prevention in elective surgery].

PMID- 15496000
TI  - [The newborn infant and hepatitis B].

PMID- 15496001
TI  - [Clinical trial registration: a statement for the International Committee of
      Medical Journal Editors].

PMID- 15496002
TI  - [Systematic alcohol intervention in hospitals].

PMID- 15496003
TI  - [Mercury in influenza vaccine].

PMID- 15496004
TI  - [Thimerosal and the occurrence of autism. Negative ecological evidence from
      Danish registry-data].

PMID- 15496005
TI  - [Treatment of hospitalized patients in a medical department with acid-suppressing
      medication].

PMID- 15496006
TI  - [Smoking, alcohol overconsumption and obesity before elective surgery. Prevalence
      and patient motivation for risk reduction].

PMID- 15496007
TI  - [Cross-sectorial audit of hepatitis B screening of pregnant women and vaccination
      of newborns born to HBsAg-positive mothers in the county of Copenhagen].

PMID- 15496008
TI  - [Efficacy of antenatal screening for hepatitis B among pregnant women in
      Denmark].

PMID- 15496009
TI  - [POEMS syndrome].

PMID- 15496010
TI  - [Histamine poisoning after eating tuna burger].

PMID- 15496011
TI  - [Recurrence of group B streptococcal infection in neonates].

PMID- 15496012
TI  - [Quality of cervical cytological tests without endocervical cells].

PMID- 15496013
TI  - [Use of acupuncture in primary health care 2].

PMID- 15496014
TI  - [Why not to do anything substantial in vitamin D deficiency?].

PMID- 15496015
TI  - 3-D imaging of the temporomandibular joint: a current perspective.

PMID- 15496016
TI  - Edentulous ridge augmentation. Part I.

PMID- 15496017
TI  - Dental implants: a macroscopic review of host tissue response.

PMID- 15496018
TI  - Measuring denture deformation: from calipers to lasers.

PMID- 15496019
TI  - Chaning times for for women in dentistry.

PMID- 15496021
TI  - [Cutaneous melanoma prevention. Modify behaviors].

PMID- 15496022
TI  - [Blockade of the renin-angiotensin system by a combination of ACE inhibitors and
      AT1 receptor antagonists].
AB  - The results issued from experimental models and randomized controlled clinical
      trials have shown that the more intense is the blockade of the renin-angiotensin
      system (RAS), the more effective is the prevention of target organ damage.
      Combined inhibition of the RAS is aimed at more complete blockade of the system
      through action at two different sites, angiotensin I converting enzyme (ACE) and
      AT1 receptors. This is achieved either by neutralizing the rise in renin and
      angiotensin (Ang) I, which follows the interruption of the Ang II-renin negative
      feed-back loop, or by directly antagonizing Ang II, whose synthesis is in part
      independent of the RAS. By comparison with higher doses of single site RAS
      blockers, a combination of an ACE inhibitor and an AT1 receptor antagonist block
      more effectively the RAS. After the demonstration of its synergistic or additive
      blood pressure lowering effects in sodium depleted normotensive subjects and
      animal models, combined blockade of the RAS was shown to be more efficient than
      single site RAS blockade: 1. in lowering blood pressure in hypertensive patients;
      2. in lowering proteinuria and possibly retarding progression of renal failure in
      patients with diabetic and non-diabetic nephropathy; 3. finally, in improving
      left ventricular remodelling, cardiac function status and cardiovascular
      morbidity and mortality in patients with congestive heart failure. The advantage
      offered by combining two RAS blockers is to increase the beneficial effect of
      cardioprotection and nephroprotection which are currently demonstrated with the
      highest doses of an ACE inhibitor or an AT1 receptor antagonist.

PMID- 15496023
TI  - [Cutaneous melanoma. The early diagnosis, a must for efficacy].

PMID- 15496024
TI  - [Epidemiology and prevention of melanoma].
AB  - Melanoma incidence and mortality are still increasing, but new leveling-off and
      even decreasing trends are detected in young women generations in a few
      countries, where intensive prevention and screening campaigns have been
      conducted. Sun avoidance remains the basis of prevention, but is facing hard
      societal resistances. Sunscreens have a more and more theoretical protective
      profile, but in the real life, their ability to prevent skin cancers is quite
      uncertain. Some pieces of the melanoma genetic puzzle have been identified, but
      are not yet useful for the practical identification of patients at high risk for
      melanoma. Early detection is still the key for improving melanoma mortality. The
      most useful signs for melanoma detection are the impression of overall
      irregularity as compared to common nevi, the "ugly duckling sign" and a recent
      change. However, a subgroup of biologically aggressive melanoma will probably
      remain out of reach of early detection, due to their very rapid growth. In order
      to promote self-detection in the general population, a cognitive strategy using
      photographs is probably more efficacious than teaching the classical "ABCD"
      algorithm.

PMID- 15496025
TI  - [Clinical aspects of cutaneous melanoma: atlas].

PMID- 15496026
TI  - [Diagnosis and follow up of cutaneous melanoma].
AB  - The early diagnosis of cutaneous melanoma alone is capable of significantly
      reducing the morbidity and mortality associated with this tumour. It is pertinent
      to all physicians who normally observe skin during the clinical examination; who
      must have a degree of suspicion for all recent or modified pigmented lesions, and
      should offer a cutaneous follow-up and advise decreased sun exposure in all
      patients with multiple naevi. The modification of a lesion, intensely black in
      colour, are the key elements which arouse suspicion of a melanoma and incite
      either its removal or a specialist opinion. The follow-up of the patient treated
      surgically for a melanoma is mainly clinical (skin, subcutaneous tissues, lymph
      node examination) but has to be consistent (more often on a trimesterly basis),
      systematic, and annual after 5 to 8 years, during the whole life of the patient
      with a high risk of a second melanoma. Equally, family members of a patient with
      a melanoma should also be systematically examined.

PMID- 15496027
TI  - [Treatment of primary and regional melanoma].
AB  - The treatment of primary melanoma and regional melanoma remains essentially the
      surgery. At the stage of primary tumor, the treatment is established from the
      data of the conference of consensus of 1995. In addition, at this stage of
      primary tumor, when the index of Breslow of the melanoma is equal or higher than
      1.5 mm like at the stage of lymph node invasion, an adjuvant treatment by
      interferon alpha after the surgery must be discussed. Chemotherapy on the other
      hand never proved reliable of its effectiveness as adjuvant treatment. In the
      future, the approaches by vaccination and cellular therapy could be interesting
      at these stages of the disease.

PMID- 15496028
TI  - [Disseminated melanoma treatment].
AB  - Disseminated melanoma is an incurable disease whose prognosis has remained
      unchanged over the past 20 years. To date, no consensus treatment has emerged. No
      treatment strategy has proved superior to dacarbazine (Deticene) monochemotherapy
      that remains considered as the reference treatment for this disease. Both
      multidrug chemotherapy and biochemotherapy have provided disappointing results,
      with poorer quality of life and no survival benefit for the patients. Other
      treatment approaches, particularly immunotherapy, remain to be investigated in
      clinical trials.

PMID- 15496029
TI  - [Patient's note card. Melanoma: be careful with sun].

PMID- 15496030
TI  - [A thesis at Necker Medical School].

PMID- 15496031
TI  - [Women's pelvic mass diagnosis].

PMID- 15496032
TI  - [Addiction and drug associated behavior. Management, substitutive therapy and
      abstinence: alcohol, tobacco, psycho-active and illicit substances. Part I.
      Tobacco].

PMID- 15496033
TI  - [Evaluation of complementary examinations in the medical process. Useful and
      useless prescriptions].

PMID- 15496034
TI  - [Evaluation of the severity and monitoring of early complications in
      multitrauma].

PMID- 15496035
TI  - [Genito-scrotal pathology in the boy and in the man].

PMID- 15496036
TI  - [Epilepsy in the child and in the adult: Second part--adult epilepsy].

PMID- 15496037
TI  - [The unusual collection of the Hospital of Sainte-Anne].

PMID- 15496038
TI  - Veterinary pharmacy practice: you can do it.

PMID- 15496039
TI  - You've got to believe! The sky is the limit--if we believe we can change our
      patient's lives.

PMID- 15496040
TI  - Casus belli. Trends in health care create a 'call to arms' for pharmacists.

PMID- 15496041
TI  - National survey of pharmacists about coronary heart disease,
      hypercholesterolemia, nonprescription statintherapy, and pharmacists' services.
AB  - OBJECTIVE: To determine the beliefs and attitudes of pharmacists about the
      significance of high blood cholesterol, coronary heart disease (CHD),
      nonprescription statin therapy for patients at moderate risk for CHD, and their
      role in support of cholesterol-lowering treatments in patients. DESIGN: Cross
      sectional survey. SETTING: Nationwide sample of licensed pharmacists in
      ambulatory practice in the United States drawn randomly from databases of the
      American Pharmacists Association. PARTICIPANTS: 104 independent pharmacists and
      169 chain pharmacists. INTERVENTION: Web-based survey. MAIN OUTCOME MEASURE:
      Respondents' indication of strong agreement with questionnaire statements
      (selecting 8, 9, or 10 on a 10-point scale). RESULTS: The survey found that 75%
      and 61% of pharmacists believed strongly that CHD and high blood cholesterol
      levels, respectively, are significant health problems facing Americans, and 60%
      believed that not enough is currently being done to reduce this risk. Pharmacists
      indicated that they very regularly advised patients about prescription and
      nonprescription treatments (75%) and encouraged adherence to them (78%); a
      smaller but substantial proportion regularly monitored patient response to
      prescription (33%) and nonprescription therapies (15%) and provided point-of-care
      cholesterol testing (7%). The survey also revealed that the majority of
      pharmacists (68%) would support consumers interested in purchasing a
      nonprescription statin product and 82% believed such a product would be more
      effective than currently available cholesterol-lowering dietary supplements.
      Pharmacists were concerned that patients pursuing nonprescription statins might
      discontinue their prescription cholesterol-lowering medications (79%), experience
      adverse effects (79%), and not be able to self-manage their use of a
      nonprescription statin product (78%). CONCLUSION: Community pharmacist members of
      APhA believe that CHD and cholesterol are important problems facing many people,
      routinely provide services that support patients who wish to self-administer
      nonprescription therapies, and would be interested in supporting consumers who
      wish to carry out therapy with a nonprescription statin.

PMID- 15496042
TI  - Men's health initiative risk assessment study: effect of community pharmacy-based
      screening.
AB  - OBJECTIVES: To determine whether community pharmacists using a risk assessment
      tool could encourage men who were overdue for a physical examination to visit a
      physician and to calculate the return on investment from the pharmacy perspective
      for offering a complimentary risk assessment service. DESIGN: 12-week,
      prospective cohort study using convenience sampling among men who visited
      participating pharmacies. SETTING: Cross-section of community pharmacies.
      PATIENTS: 382 men aged 25-74 years with potential health risks that were
      untreated or uncontrolled, or who had not had a physical examination within the
      past year. INTERVENTION: Screening for specific health risks with or without
      telephone follow-up. MAIN OUTCOME MEASURE: Overall male patient response to
      pharmacist recommendations for follow-up medical care. RESULTS: Of 382 men
      identified by the Men's Health Risk Assessment Tool (MHRAT) as being at risk for
      1,194 significant health conditions (mean, 3.1 conditions per patient), 69% had
      not received a physical examination from a physician for a period ranging from
      more than 1 year to 22.6 years. Of men who were recommended to make an
      appointment, 64% were seen by a physician or were waiting on a scheduled
      appointment at the end of the study. No differences were seen between the
      telephone intervention group and the control group in rates of obtaining a
      physician examination. CONCLUSION: A positive public health initiative involving
      community pharmacists was demonstrated in this study. Community pharmacists had a
      significant impact on motivating men to see a physician for follow-up care once a
      potential health risk was identified. The MHRAT and the pharmacist recommendation
      or patient education were the motivating factors and not follow-up telephone
      interventions by the pharmacist. Given community pharmacists' unique
      accessibility, an enormous opportunity exists for community pharmacists to raise
      awareness of men's health care and influence men's health behavior.

PMID- 15496043
TI  - Knowledge and attitudes about smoking cessation among pharmacy technicians.
AB  - OBJECTIVE: To evaluate the knowledge and attitudes of pharmacy technicians before
      and after attending a continuing education program about smoking cessation.
      DESIGN: A pre/post survey of a single group. SETTING: Two statewide meetings of
      the Iowa Pharmacy Association. PARTICIPANTS: Pharmacy technicians. INTERVENTION:
      One 2-hour continuing education (CE) course about smoking cessation for pharmacy
      technicians. MAIN OUTCOME MEASURES: Changes in scores before and after the CE
      sessions among three domains (knowledge, efficacy, and outcome) of a validated
      survey instrument. RESULTS: Fifty-one technicians completed both the presession
      and postsession questionnaire. For the three survey domains, technicians'
      knowledge (P = .034), efficacy (P < .001), and outcome (P < .001) showed
      significant improvement between the presession and postsession surveys (Wilcoxon
      signed rank test). CONCLUSION: Pharmacy technicians who attended a CE program on
      smoking cessation improved their knowledge, attitudes, and self-confidence in
      helping smokers quit. Additional research should be conducted to test the role of
      pharmacy technicians in smoking cessation promotion.

PMID- 15496044
TI  - Variability in tablet fragment weights when splitting unscored cyclobenzaprine 10
      mg tablets.
AB  - OBJECTIVE: To determine the weight variation and calculated dosing variability of
      tablet fragments upon splitting unscored cyclobenzaprine hydrochloride 10 mg
      tablets using two common tablet splitting devices. DESIGN: Comparative
      pharmaceutics study. SETTING: Pharmacy school laboratory. PARTICIPANTS: Not
      applicable. INTERVENTIONS: Unscored cyclobenzaprine hydrochloride 10 mg tablets
      from one generic manufacturer were split with a tablet splitter or a kitchen
      knife by a licensed pharmacist and two doctor of pharmacy students (n = 15
      tablets for each method per participant). MAIN OUTCOME MEASURES: Fragment weights
      (FWs) were compared with the theoretical weights (TWs), which were calculated as
      one half of the mean weight of the tablets used in each part of the experiment;
      means, relative standard deviations (RSDs), and percentages of TW were also
      calculated. RESULTS: The mean weight before splitting the 45 tablets with the
      tablet splitter was 136.6 +/- 2.1 mg (TW = 68.3 mg). The mean FW after splitting
      was 67.9 +/- 7.9 mg. The RSD of 11.6% corresponded to a range of 69.4% to 130.2%
      of the TW and an estimated drug content of the split fragments between 3.47 mg
      and 6.51 mg. The mean weight before splitting the 45 tablets cut with a kitchen
      knife was 136.6 +/- 2.0 mg (TW = 68.3 mg). The mean FW was 68.0 +/- 15.7 mg with
      a RSD of 23.2%, corresponding to a range of 49.9% to 149.5% of the TW and an
      estimated drug content of the split fragments between 2.49 mg and 7.48
      CONCLUSION: Tablet fragments obtained after splitting this generic
      cyclobenzaprine 10 mg product varied considerably in weight and estimated drug
      content. Accordingly, splitting cyclobenzaprine 10 mg tablets to achieve 5 mg
      doses could result in unpredictable dosing and therapeutic response.

PMID- 15496045
TI  - Comparison of ease of swallowing of dietary supplement products for age-related
      eye disease.
AB  - OBJECTIVE: To examine patients' perceptions on the relative importance of the
      physical characteristics and appearance of dietary supplements, and to evaluate
      two supplements with the same combination of vitamins and minerals used in the
      Age-Related Eye Disease Study (AREDS) with respect to ease of swallowing and
      other features in elderly patients. DESIGN: A single-site, single-visit,
      crossover design, subject-masked comparison of two dietary supplements (ICaps
      AREDS Formula--Alcon; Ocuvite PreserVision-Bausch & Lomb). SETTING: Ophthalmology
      practice. PATIENTS: 50 patients aged 50 years or older. INTERVENTIONS: Patients
      ranked the importance of eight physical characteristics of a vitamin tablet or
      capsule (ease of swallowing, size, shape, color, smell, coating, texture, and
      taste) irrespective of the test products used in the study and then took both
      test products randomly and were asked to indicate which product they preferred
      based on the same eight characteristics. MAIN OUTCOME MEASURES: Overall patient
      preference and preference for swallowing two tablets at once. RESULTS: The
      highest rated (most important) characteristic in a vitamin supplement was ease of
      swallowing, with a median score of 9.0 on a 0-10 visual analogue scale. The
      characteristic of least importance was tablet color, with the lowest median score
      of 1.0. Statistically significant differences were detected between the products
      with regard to preferences for ease of swallowing, swallowing two tablets at
      once, size, and coating (P < or = .0001). Significantly more patients preferred
      the ICaps AREDS formula to Ocuvite PreserVision with respect to these
      characteristics and overall preference (P < .001). Age, gender, and previous
      vitamin use were contributing factors in the rating of physical characteristics
      and tablet preferences. CONCLUSION: Based on the results of this study, ease of
      swallowing is the most important characteristic of dietary supplement tablets for
      elderly patients, followed by taste, size, and smell. Significant differences in
      preference exist between the study products, which contain similar formulations
      but have different physical characteristics.

PMID- 15496046
TI  - Efficacy of zinc against common cold viruses: an overview.
AB  - OBJECTIVE: To review the laboratory and clinical evidence of the medicinal value
      of zinc for the treatment of the common cold. DATA SOURCES: Published articles
      identified through Medline (1980-2003) using the search terms zinc, rhinovirus,
      and other pertinent subject headings. Additional sources were identified from the
      bibliographies of the retrieved articles. STUDY SELECTION: By the author. DATA
      EXTRACTION: By the author. DATA SYNTHESIS: Human rhinoviruses, by attaching to
      the nasal epithelium via the intracellular adhesion molecule-1 (ICAM-1) receptor,
      cause most colds. Ionic zinc, based on its electrical charge, also has an
      affinity for ICAM-1 receptor sites and may exert an antiviral effect by attaching
      to the ICAM-1 receptors in the rhinovirus structure and nasal epithelial cells.
      Clinical tests of zinc for treatment of common colds have been inconsistent,
      primarily because of study design, blinding, and lozenge contents. Early
      formulations of lozenges also were unpalatable. In three trials with similar
      study designs, methodologies, and efficacy assessments, zinc effectively and
      significantly shortened the duration of the common cold when it was administered
      within 24 hours of the onset of symptoms. Recent reports of trials with zinc
      gluconate administered as a nasal gel have supported these findings; in addition,
      they have shown that treatment with zinc nasal gel is effective in reducing the
      duration and severity of common cold symptoms in patients with established
      illness. CONCLUSION: Clinical trial data support the value of zinc in reducing
      the duration and severity of symptoms of the common cold when administered within
      24 hours of the onset of common cold symptoms. Additional clinical and laboratory
      evaluations are warranted to further define the role of ionic zinc for the
      prevention and treatment of the common cold and to elucidate the biochemical
      mechanisms through which zinc exerts its symptom-relieving effects.

PMID- 15496047
TI  - Eplerenone: selective aldosterone antagonism in management of cardiovascular and
      renal disease.
AB  - OBJECTIVE: To review the pharmacology, safety, and efficacy data, as well as
      therapeutic use of eplerenone (Inspra-Pfizer) for management of cardiovascular
      and renal disease. DATA SOURCES: A Medline search (January 1980-July 2003) was
      performed using eplerenone, aldosterone, aldosterone antagonist, spironolactone,
      and other pertinent terms. Additional articles were identified from
      bibliographies of retrieved articles. STUDY SELECTION: All retrievable studies
      and review articles discussing the pharmacology, safety, and efficacy of
      eplerenone were evaluated. DATA EXTRACTION: By the authors. DATA SYNTHESIS: The
      detrimental role of the renin-angiotensin-aldosterone system (RAAS) in the
      pathophysiology of cardiovascular and renal disease has been well documented.
      Until recently, however, the direct injurious effects of aldosterone on
      nonclassical tissues such as the brain, heart, and vasculature have been
      overlooked. Although angiotensin-converting enzyme (ACE) inhibitors and
      angiotensin II receptor blockers (ARBs) significantly reduce morbidity and
      mortality associated with heart disease, preliminary data suggest further benefit
      with additional aldosterone blockade. The nonselective aldosterone antagonist
      spironolactone has demonstrated profound morbidity and mortality benefit in heart
      failure patients, but since its adverse event profile makes it unattractive to
      patients with milder disease, the need for a selective aldosterone receptor
      antagonist is evident. Preclinical studies with eplerenone, a recently approved
      selective aldosterone receptor antagonist, demonstrate a protective effect on
      nonclassical tissues, thus reducing injury associated with long-term unopposed
      aldosterone exposure. Early clinical trials with eplerenone have demonstrated
      additional benefit in hypertension, heart failure, and nephropathy, although long
      term morbidity and mortality outcome data in patients with various levels of
      disease severity are necessary to define the role of eplerenone in current
      cardiovascular pharmacotherapy. CONCLUSION: Eplerenone offers a new selective
      approach to optimizing aldosterone blockade. The availability of additional
      morbidity and mortality outcome data in various cardiovascular conditions will
      provide further insights into its role in clinical practice.

PMID- 15496048
TI  - White paper: value of specialty certification in pharmacy.
AB  - OBJECTIVE: To address the value of Board of Pharmaceutical Specialties (BPS)
      certification, particularly as perceived by different stakeholders (pharmacists,
      employers, government, and academia), and to draw a parallel between
      specialization and certification in pharmacy and in medicine. DATA SOURCES:
      Electronic databases (Medline, International Pharmaceutical Abstracts,
      Sociological Abstracts), associations/health care organizations Web sites,
      outside reports, and clinical pharmacists involved in certification processes.
      STUDY SELECTION: Studies and reports that addressed the value of specialty
      certification were selected by the authors. DATA EXTRACTION: By the authors. DATA
      SYNTHESIS: Pharmacists with specialty certification report enhanced feelings of
      self-worth, improved competence, and greater marketability. Other values of
      certification include increased acceptance by health care professionals, salary
      increases, and job promotions. Employers have acknowledged board-certified
      pharmacists through public recognition, increase in responsibility, and some
      types of monetary compensation. In some governmental organizations, certified
      pharmacists receive salary raises and are granted prescribing authority. However,
      the overall value of specialty certification in pharmacy as perceived by the
      public or payers lags behind when compared with the status of specialty
      certification in medicine. CONCLUSION: Board-certified pharmacists appreciate the
      value of pharmacy specialty certification, and in a number of organizations and
      practice settings, board-certified pharmacists are perceived as valuable. Still,
      unlike board-certified physicians, board-certified pharmacists are not widely
      recognized outside or even within the pharmacy profession. To address this
      challenge, board-certified pharmacists ought to market their services to assure
      that other stakeholders recognize their value.

PMID- 15496049
TI  - Advancing pharmacy practice through research: a 2004 perspective.
AB  - OBJECTIVE: To share the current reflections, perspectives, and recommendations of
      the Pharmacy Practice Research Roundtable about a research agenda for pharmacy
      practice in the United States. DATA SOURCES: Peer-reviewed medical literature,
      national and international developments relating to health care, laws and
      regulations affecting pharmacy practice, information provided by invited guests,
      and personal experiences of roundtable members. SUMMARY: Current realities with
      the potential to affect pharmacy practice relate to strategies for pursuing
      pharmacy practice research. Emerging roles and activities of pharmacists in
      health systems and the community are identified in this article. Based on
      consideration of the realities, strategies, and new roles, priority areas for
      pharmacy practice research are identified. Recommendations for research emphasis
      include the following: (1) define medication therapy management services that
      relate to medication safety, improved management of chronic disease, and
      implementation of a Medicare ambulatory drug benefit; (2) evaluate pharmacy
      practice models from external and internal perspectives; (3) differentiate
      patient groups based on their need for, access to, and affinity for pharmacist
      services; (4) define achievable roles and responsibilities for patients in
      medication use; (5) provide a deeper understanding about the professional
      workforce in pharmacy; (6) examine the gap between academic practice models and
      actual practice and test strategies to reduce the gap; and (7) evaluate the
      applicability to the United States of evolving pharmacy practice activities in
      other countries. CONCLUSION: A national pharmacy practice research agenda should
      be pursued in the context of those issues that are influencing health care.

PMID- 15496050
TI  - Community pharmacists' counseling about metformin-associated lactic acidosis.

PMID- 15496051
TI  - Simple additions to the pharmacy waiting area may increase patient satisfaction.

PMID- 15496052
TI  - Henry Armitt Brown Dunning (1877-1962): pharmacy philanthropist and father of the
      APhA Foundation.

PMID- 15496053
TI  - Health care workers and influenza vaccine: first do no harm, then do the right
      thing.

PMID- 15496054
TI  - Hypervalent iodine-mediated vicinal syn diazidation: application to the total
      synthesis of (+/-)-dibromophakellstatin.
AB  - [reaction: see text] The total synthesis of (+/-)-dibromophakellstatin is
      described. The molecule is constructed from a key syn-diazide, formed by a
      hypervalent iodine-mediated diazidation of a dihydrodipyrrolopyrazinone ring
      structure.

PMID- 15496055
TI  - Low-temperature deacylation of N-monosubstituted amides.
AB  - [reaction: see text] The (PhO)(3)P.Cl(2) reagent, prepared in situ by titrating a
      solution of triphenyl phosphite with chlorine, is used to convert N
      monosubstituted amides into their corresponding amines. The reaction, if compared
      to other traditional methods, shows the advantage of very mild conditions and low
      temperature (-30 degrees C-->rt).

PMID- 15496057
TI  - Oligobisvelcraplex: self-assembled linear oligomer by solvophobic pi-pistacking
      interaction of bisvelcrands based on resorcin[4]arene.
AB  - [reaction: see text] Bisvelcrand 3 based on resorcin[4]arene was obtained by a
      stepwise route, and the formation of oligobisvelcraplex 3(n) by solvophobic pi
      pistacking interaction was observed. (1)H NMR spectroscopic studies revealed that
      DeltaG(++)(pseudorotation) of oligobisvelcraplex 3(n) is 16.7 kcal mol(-1) in
      C(6)D(5)NO(2) solution. The pulsed field gradient spin-echo (PGSE) NMR experiment
      and VPO experiment showed that the number of aggregation (n) ranges from 7 to 10
      in CHCl(3) solution at 298 K. In high concentration, bisvelcrand 3 tends to form
      gels or fiber.

PMID- 15496056
TI  - Synthesis of the A,B,C-ring system of hexacyclinic acid.
AB  - [structure: see text] The synthesis of the A,B,C-ring system (2) of hexacyclinic
      acid (1) is achieved starting from a selective Diels-Alder reaction followed by
      vinyl cuprate addition. The diastereoselective reduction of the ketone carbonyl
      at C16 could be achieved with LiAlH(4). An intramolecular Michael addition
      established the ring system stereoselectively, providing access to the selective
      generation of 9 out of the 14 stereocenters of hexacyclinic acid.

PMID- 15496058
TI  - One-pot synthesis of 1,4-disubstituted 1,2,3-triazoles from in situ generated
      azides.
AB  - [reaction: see text] 1,4-Disubstituted 1,2,3-triazoles are obtained in excellent
      yields by a convenient one-pot procedure from a variety of readily available
      aromatic and aliphatic halides without isolation of potentially unstable organic
      azide intermediates.

PMID- 15496059
TI  - Synthesis of the trisaccharide repeating unit of the atypical O-antigen
      polysaccharide from Danish Helicobacter pylori strains employing the 2'
      carboxybenzyl glycoside.
AB  - [reaction: see text] Synthesis of the unique trisaccharide repeating unit of the
      O-polysaccharide of the lipopolysaccharide from Danish Helicobacter pylori
      strains has been accomplished. Key steps include the coupling of three
      monosaccharide moieties by glycosylations employing the 2'-carboxybenzyl
      glycoside method. Also presented is a method for the synthesis of the novel
      branched sugar, 3-C-methyl-D-mannose, which is one of three monosaccharide
      components.

PMID- 15496060
TI  - Diels-Alder reaction between indoles and cyclohexadienes photocatalyzed by pi,pi
      aromatic ketones.
AB  - [structure: see text] Diels-Alder reactions between indoles and cyclohexadienes
      can be photocatalyzed by benzoylthiophenes. Both experimental and theoretical
      studies show that the reactions occur through ternary excited triplet state
      complexes (triplet triplexes).

PMID- 15496061
TI  - Studies toward the synthesis of luminacin D: assembly of simplified analogues
      devoid of the epoxide displaying antiangiogenic activity.
AB  - [reaction: see text] A series of structurally simplified luminacin analogues
      devoid of the epoxide ring are assembled in a stereocontrolled manner from 2,4
      dimethoxybenzaldehyde using a syn-selective aldol reaction as the key step. The
      success of the approach is critically dependent on the nature and extent of the
      alcohol protecting groups. The synthetic analogues inhibit VEGF-stimulated
      angiogenesis in an in vitro assay indicating that the epoxide is not essential
      for biological activity in this compound class.

PMID- 15496062
TI  - A novel stereospecific synthesis of glycosyl cyanides from 1,2-O-sulfinyl
      derivatives.
AB  - [reaction: see text] An efficient synthesis of 1,2-trans-glycosyl cyanides via
      1,2-O-sulfinyl monosaccharides is described. Such S(N)2-type displacements at the
      anomeric center are stereospecific and are best performed with sodium cyanide in
      the presence of ytterbium triflate. Significantly, the resulting 1,2-trans
      glycosyl cyanides have a free hydroxyl group at C-2 ready for further
      modification.

PMID- 15496063
TI  - Highly (Z)-selective synthesis of beta-monosubstituted alpha,beta-unsaturated
      cyanides using the peterson reaction.
AB  - [reaction: see text] The Peterson reaction between (t-BuO)Ph(2)SiCH(2)CN and
      various aldehydes furnishes the corresponding beta-monosubstituted alpha,beta
      unsaturated cyanides with high Z selectivity (Z:E = 92:8 to >98:2).

PMID- 15496064
TI  - New scavenger resin for the reversible linking and monoprotection of
      functionalized aromatic aldehydes.
AB  - [reaction: see text] Polymer-supported benzylhydrazines were synthesized using
      poly(ethylene glycol) acrylamide (PEGA) resin. They can be used to scavenge
      electrophiles reactive with hydrazine. Especially aromatic aldehydes can be
      captured selectively, monoprotected, and reversibly linked in the presence of
      other functional groups, including electrophilic ones. Various reactions can be
      performed on these protectively linked aldehydes, which afterward can be released
      either with full restoration of the aldehyde function or, alternatively, with
      simultaneous conversion.

PMID- 15496065
TI  - The first trisaza-bridged [60]fulleroid: drilling a hole on the fullerene.
AB  - [reaction: see text] Two types of trisaza-bridged [60]fulleroids have been
      synthesized for the first time. By means of (13)C NMR, (1)H NMR, MALDI-TOF MS,
      FTIR, UV-vis, and 2D-NMR (gHSQC, gHMBC, and NOSEY) spectroscopy, they have been
      shown to be tris[6,5]-opened-aza-bridged adducts with substituents on the same
      five-membered ring with C(s)() symmetry. Some data of nonlinear optics and
      electrochemistry for the product are also reported.

PMID- 15496066
TI  - A new halopropargylation of alkynes promoted by boron trihalides. highly stereo-
      and regioselective syntheses of substituted (Z)-1-halo-1,4-enyne derivatives.
AB  - [reaction: see text] A new halopropargylation of alkynes promoted by boron
      trihalides has been developed. Reactions of (Z)-2-halo-1-vinylboron dihalides
      (generated in situ via reaction of alkynes with boron trihalides) with lithium
      propargyloxides in CH(2)Cl(2) at room temperature produce the corresponding (Z)-1
      halo-1,4-enynes in modest to good yields.

PMID- 15496067
TI  - Biogenetically inspired synthesis of marine C6N4 2-aminoimidazole alkaloids: Ab
      initio calculations, tautomerism, and reactivity.
AB  - [reaction: see text] A simple synthesis of the fused tetrahydro-imidazopyridine
      13 was accomplished via selective addition of protected guanidine to N
      carbomethoxy-1,2-dihydropyridine in the presence of bromine. Base-mediated
      semicleavage of the aminal gave 4-substituted 2-aminoimidazole 14. With this new
      method, natural marine metabolite 3-amino-1-(2-aminoimidazol-4-yl)-prop-1-ene (1)
      and derivatives may now be prepared from pyridine. Ab initio calculations of the
      energies of tautomers I-IV and deuteration experiments have provided insight into
      their reactivity.

PMID- 15496068
TI  - Cobalt(I)-mediated [2 + 2 + 2] cyclization of allenediynes toward a
      diastereoselective approach to 11-aryl steroid skeletons.
AB  - [reaction: see text] An 11-aryl steroid skeleton has been built in one step with
      a simultaneous introduction of the substituents at both C11 and C10 in 48%
      overall yield from a trans-allenediyne, whereas a formal Alder ene reaction
      leading to a bicyclic yne-trienic compound becomes the major process from the cis
      allenediyne.

PMID- 15496069
TI  - Synthesis of new 2',3'-dideoxy-6',6'-difluoro-3'-thionucleoside from gem
      difluorohomoallyl alcohol.
AB  - [reaction: see text] 2',3'-Dideoxy-6',6'-difluoro-3'-thionucleoside 1b, an
      analogue of 3Tc that has high biological activities against HIV and HBV, has been
      synthesized from gem-difluorohomoallyl alcohol 3 in an efficient way. The key
      intermediate 4-amino-3,3-difluorotetrahydrothiophen-2-ylmethyl benzoate 15 was
      prepared from 2,2-difluoro-1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]but-3-en-1-ol 3
      in 11 steps. The construction of pyrimidine ring with the amino group of compound
      15 gave the target compound 1.

PMID- 15496070
TI  - Hyperconjugative effects in the stereoselective ring-opening reactions of
      oxetenoxides.
AB  - [reaction: see text] Unexpectedly, the pattern of the stereoselectivity in the
      ring-opening reactions of lithium oxetenoxides is not consistent with the
      bulkiness of substituents, and both the bulkier tert-butyl and silyl substituents
      favor inward rotation. With the aid of B3LYP calculations, the hyperconjugative
      interaction between the breaking C(1)-O sigma and its anti-periplanar Z-Me (Z =
      Si or C) sigma orbital is found to be responsible among the secondary orbital
      interactions of the substituents and the oxetene moiety.

PMID- 15496071
TI  - A set of nonpolar thymidine nucleoside analogues with gradually increasing size.
AB  - [structure: see text] We describe a series of nonpolar nucleoside analogues
      having similar shapes and gradually increasing size. The structure of the
      nucleobase thymine was mimicked with toluene derivatives, replacing O2/O4 with
      hydrogen, fluorine, chlorine, bromine, and iodine. Glycosidic bonds were formed
      by reactions of lithiated 2,4-dihalotoluenes with a deoxyribonolactone
      derivative. Structural analysis by NMR showed similar conformations across the
      series. The compounds are useful for study of the biological recognition of
      nucleotides and nucleic acids.

PMID- 15496072
TI  - Samarium diiodide-induced asymmetric synthesis of optically pure unsymmetrical
      vicinal diamines by reductive cross-coupling of nitrones with N-tert
      butanesulfinyl imines.
AB  - [reaction: see text] An efficient method for the preparation of optically pure
      unsymmetrical vicinal diamines by the SmI(2)-induced reductive cross-coupling of
      nitrones with chiral N-tert-butanesulfinyl imines was developed. This is the
      first successful example of the highly diastereoselective and enantioselective
      cross-coupling between two different imine species. It provides a straightforward
      access to enantiopure unsymmetrical vicinal diamines that are widely applicable
      in asymmetric synthesis.

PMID- 15496073
TI  - End-capping of a pseudorotaxane via Diels-Alder reaction for the construction of
      C60-terminated [2]rotaxanes.
AB  - [reaction: see text] The Diels-Alder reaction of various dienophiles such as
      C(60) with a pseudorotaxane having a sultine moiety afforded corresponding
      [2]rotaxanes in moderate yields. The introduction of a porphyrin moiety on the
      wheel component considerably enhanced the efficiency of the end-capping reaction
      with C(60).

PMID- 15496074
TI  - Metathesis of structurally preorganized bivalent carbohydrates. Synthesis of
      macrocyclic and oligomeric scaffolds.
AB  - [reaction: see text] Bivalent carbohydrate substrates for metathesis were
      synthesized from glucuronic acid and phenylene-1,4-diamine. The substrate
      secondary structure depends on whether secondary or tertiary amides are present,
      and this influences the course of the metathesis reaction leading to novel
      multivalent scaffolding. Molecular modeling suggests that a very rigid
      macrocyclic scaffold has potential for the development of alpha-helix
      peptidomimetics.

PMID- 15496075
TI  - Synthesis of novel quinaldine-based squaraine dyes: effect of substituents and
      role of electronic factors.
AB  - [reaction: see text] Condensation of squaric acid with quinaldinium salts
      containing electron-donating substituents gave only the semisquaraines. However,
      with salts possessing electronegative and electron-withdrawing groups, the
      squaraine dyes were isolated in quantitative yields. The semisquaraines formed
      undergo condensation with highly nucleophilic salts yielding the unsymmetrical
      squaraine dyes. These results demonstrate the role of electronic factors and
      provide valuable information for the design of efficient squaraine-based
      sensitizers that can have potential applications in photodynamic therapy.

PMID- 15496076
TI  - Effect of halogenation on edge-face aromatic interactions in a beta-hairpin
      peptide: enhanced affinity with iodo-substituents.
AB  - [reaction: see text] In a model beta-hairpin peptide, we have found that the
      favorable interaction of cross-strand aromatic rings can be enhanced by up to 1
      kcal mol(-1) with halogen substituents. It appears that the polarizability of the
      halogen atoms accounts for the increase in stability and that there is a direct
      interaction between the N-terminal phenylalanine and the halogen atom. Thermal
      denaturation studies indicate that the interaction is enthalpically driven with
      an associated entropic cost. These findings have relevance to areas of molecular
      recognition and drug design.

PMID- 15496077
TI  - Asymmetric catalytic synthesis of enantiopure N-protected 1,2-amino alcohols.
AB  - [reaction: see text] The asymmetric aminolytic kinetic resolution (AKR) of
      racemic terminal epoxides using carbamates as the nucleophile catalyzed by
      (salen)Co(III) complex provides a practical and straightforward method for the
      synthesis of both aliphatic and aromatic N-Boc- or N-Cbz-protected 1,2-amino
      alcohols in almost enantiomerically pure form (ee >/= 99%). The AKR uses an
      easily accessible catalyst and inexpensive starting materials, and the reactions
      are conveniently carried out at room temperature under an air atmosphere.

PMID- 15496078
TI  - Efficient synthesis of acylsilanes using morpholine amides.
AB  - [reaction: see text] A general synthesis of acylsilanes from the corresponding
      morpholine amides and silyllithium species is described. The use of morpholine
      amides is economical and prevents over-addition by the silyl nucleophile. The
      procedure cleanly affords acylsilanes in good yields and circumvents the use of
      stoichiometric copper(I) cyanide typically employed to synthesize these compounds
      from acid chlorides.

PMID- 15496079
TI  - Palladium-catalyzed cross-coupling of pyrrole anions with aryl chlorides,
      bromides, and iodides.
AB  - [reaction: see text] A general method for the conversion of pyrrole anions to 2
      arylpyrroles has been developed. Using a palladium precatalyst and sterically
      demanding 2-(dialkylphosphino)biphenyl ligands, (pyrrolyl)zinc chloride may be
      cross-coupled with a wide range of aryl halides, including aryl chlorides and
      aryl bromides, at low catalyst loadings and under mild conditions. A high degree
      of steric hindrance is tolerated. Certain ring-substituted pyrrole anions have
      also been arylated with aryl bromide substrates.

PMID- 15496080
TI  - Total synthesis of the novel, biologically active epoxyquinone dimer (+/-)
      torreyanic acid: a biomimetic approach.
AB  - [reaction: see text] A total synthesis of the complex, biologically active,
      dimeric natural product (+/-)-torreyanic acid, which is composed of seven rings
      and laced with dense, variegated oxy-functionalization, has been accomplished
      from readily available allyl-substituted p-benzoquinone 8. Our synthetic
      stratagem involves crafting an epoxyquinone monomer for use in a biomimetic
      cascade process involving tandem a 6pi electrocyclization and a Diels-Alder
      dimerization.

PMID- 15496082
TI  - Double phosphinylation of propargylic alcohols: a novel synthetic route to 1,2
      bis(diphenylphosphino)ethane derivatives.
AB  - [reaction: see text] Double phosphinylation of propargylic alcohols with
      diphenylphosphine oxide in the presence of a thiolate-bridged diruthenium complex
      as catalyst gives the corresponding 2,3-bis(diphenylphosphinyl)-1-propenes in
      high yields with a complete selectivity.

PMID- 15496081
TI  - Total syntheses of (+)-cylindricines C-E and (-)-lepadiformine through a common
      intermediate derived from an aza-Prins cyclization and Wharton's rearrangement.
AB  - [reaction: see text] Enantioselective total syntheses of (+)-cylindricines C-E
      and (-)-lepadiformine through a common tricyclic intermediate are described here.
      These syntheses are concise and feature an aza-Prins cyclization and a seldom
      used Wharton rearrangement en route to the common intermediate.

PMID- 15496083
TI  - Tandem oxidation processes for the preparation of functionalized cyclopropanes.
AB  - [reaction: see text] A novel manganese dioxide-mediated tandem oxidation process
      (TOP) has been developed which allows the direct conversion of allylic alcohols
      into cyclopropanes, the intermediate aldehydes being trapped in situ with a
      stabilized sulfur-ylide. This methodology has been applied successfully to a
      variety of allylic alcohols and to a formal synthesis of the simple, naturally
      occurring lignan, (+/-)-picropodophyllone.

PMID- 15496084
TI  - An efficient synthetic route to glycoamino acid building blocks for glycopeptide
      synthesis.
AB  - [reaction: see text] Chemical glycopeptide synthesis requires access to gram
      quantities of glycosylated amino acid building blocks. Hence, the efficiency of
      synthesis of such building blocks is of great importance. Here, we report a fast
      and highly efficient synthetic route to Fmoc-protected asparaginyl glycosides
      from unprotected sugars in three steps with high yields. The glycosylated amino
      acids were successfully incorporated into target glycopeptides 7 and 8 by
      standard Fmoc solid-phase peptide synthesis.

PMID- 15496085
TI  - Stereoselective synthesis of Baylis-Hillman-type adducts via allenolates
      generated by acyl migration.
AB  - [reaction: see text] The rearrangement of the carbamoyl group in allenyl
      carbamate 1 in the presence of n-BuLi in situ generates the allenolate 3, which
      is subsequently intercepted with aromatic aldehydes furnishing (Z)- or (E)
      configured Baylis-Hillman-type adducts 4 or 5. The double bond isomers can be
      interconverted by a retro aldol-type reaction.

PMID- 15496086
TI  - Novel odd/even effect of alkylene chain length on the photopolymerizability of
      organogelators.
AB  - [reaction: see text] Starting from diactylene diacarboxylic acids, we have
      synthesized a series of photopolymerizable organogelators that possess simple
      amide structures, different alkylene chain lengths, and either optically active
      or racemic 3,7-dimethyl-1-octylamine units. The alkylene chain length of these
      compounds exhibits a prominent odd/even effect with respect to the
      photopolymerization in the gel state and is accompanied by a stereostructural
      effect on the gelation ability.

PMID- 15496087
TI  - Likonides A and B: new ansa farnesyl quinols from the marine sponge Hyatella sp.
AB  - [structure: see text] Two novel ansa farnesyl quinols, designated likonides A and
      B, were isolated together with avarone from the Kenyan sponge Hyatella sp. The
      compounds are of a unique ansa structure. The structures and stereochemistry of
      the compounds were elucidated by interpretation of MS, two-dimensional NMR, and
      CD experiments.

PMID- 15496088
TI  - C6H4 valence bond isomers: a reactive bicyclopropenylidene.
AB  - [reaction: see text] The simple bicyclopropenylidene derivative 21b, stabilized
      by fusion into naphthalene, results from reaction of dimesitylcyclopropenone 20b
      with the 1-trimethylsilyl-1H-cyclopropa[b]naphthalenyl anion. Although unstable
      in air, the molecule survives ambient conditions long enough for separation and
      mass spectral characterization. Aerial oxidation of 21b leads to 2,3
      dimesitylanthracene-1,4-dione 22b whose X-ray crystal structure has been
      determined. While diphenylcyclopropenone 20a does not give identifiable products,
      the di-tert-butyl analogue 20c gives quinone 22c but in lower yield.

PMID- 15496089
TI  - Syntheses of stereochemically diverse nine-membered ring-containing biaryls.
AB  - [reaction: see text] A library of nine-membered, biaryl-containing rings has been
      synthesized in parallel on polystyrene macrobeads. Dimeric medium rings were
      shown to be accessible via a regio- and stereoselective double cyclization.

PMID- 15496090
TI  - Total synthesis of eupomatilones 4 and 6: structurally rearranged and
      atropisomerically fluxional lignan natural products.
AB  - [structure: see text] A convergent and diastereocontrolled total synthesis of
      eupomatilones 4 and 6 is reported and was based on a diastereoselective
      hydroboration/oxidation sequence and a convergent Lipshutz biarylcuprate cross
      coupling reaction. The structure of eupomatilone 6 is revised.

PMID- 15496091
TI  - An aza-Achmatowicz approach toward the hydroxylated piperidine alkaloids (+/-)
      azimic acid and (+/-)-deoxocassine.
AB  - [reaction: see text] The synthesis of several cis-2,3,6-trisubstituted
      piperidines has been developed employing the aza-Achmatowicz oxidation as the key
      reaction step. Its usage is illustrated by the facile synthesis of the piperidin
      3-ol alkaloids (+/-)-deoxocassine and (+/-)-azimic acid.

PMID- 15496092
TI  - Investigation of the origin of C2 units in biosynthesis of streptolydigin.
AB  - [reaction: see text] Isotope labeling studies show that malonate, not acetate,
      furnishes all four C(2) units in the acyltetramic acid streptolydigin. The
      results are compared with those for pramanicin, and implications for the
      biosynthetic pathway are discussed.

PMID- 15496093
TI  - Oxygen-promoted palladium(II) catalysis: facile C(sp2)-C(sp2) bond formation via
      cross-coupling of alkenylboronic compounds and olefins.
AB  - [reaction: see text] Oxygen-promoted Pd(II) catalysis facilitated the synthesis
      of conjugated dienes by cross-coupling of alkenylboronic compounds and various
      olefins including highly substituted alkenes and cyclohexenone. Under mild
      conditions, these versatile reactions were efficient and highly stereoselective.

PMID- 15496094
TI  - Palladium-catalyzed tandem cyclization/suzuki coupling reaction of 1,2,7-trienes.
AB  - [reaction: see text] A Pd(0)-catalyzed 1,2,7-triene cyclization/arylation cascade
      reaction was realized via pi-allylpalladium intermediate formation and a
      subsequent Suzuki coupling reaction to preferentially give a five-membered ring
      product with a stereodefined exocyclic double bond. Excellent cis/trans
      selectivity was achieved (only cis-3 was isolated) with heteroatom-tethered 1,2,7
      triene substrates.

PMID- 15496095
TI  - Synthesis of the bryostatin 1 northern hemisphere (C1-C16) via desymmetrization
      by ketalization/ring-closing metathesis.
AB  - [reaction: see text] Synthesis of the northern hemisphere (C1-C16) of bryostatin
      1, a potent anticancer agent, has been accomplished in 14 steps and 11% overall
      yield via desymmetrization by ketalization/ring-closing metathesis. A 2,9
      dioxabicyclo[3.3.1]nonane template facilitated stereoselective A-ring
      functionalization, while an efficient hetero-Diels-Alder reaction was used to
      elaborate the B-ring.

PMID- 15496096
TI  - A 2:1 coupling reaction of arynes with aldehydes via o-quinone methides:
      straightforward synthesis of 9-arylxanthenes.
AB  - [reaction: see text] A novel coupling reaction, where an aldehyde and two molar
      amounts of an aryne are assembled selectively, has been demonstrated to afford
      diverse 9-arylxanthene derivatives in one step. o-Quinone methide arising from
      the [2 + 2] cycloaddition of an aldehyde with an aryne was postulated as a
      transient intermediate.

PMID- 15496097
TI  - Silylstannylation of highly functionalized acetylenes. synthesis of precursors
      for annulations via radical or Heck reactions.
AB  - [reaction: see text] Pd-catalyzed silylstannylation of acetylenes tolerates a
      variety of reactive functional groups (aldehydes, nonterminal acetylenes,
      epoxides, activated and unactivated olefins), providing easy access to precursors
      that can be converted into carbocyclic and heterocyclic compounds via free
      radical or Heck reactions. Examples of the synthesis of pyrrolidines, bicyclic
      beta-lactams, hydrindanes, and tetrahydrofurans are described.

PMID- 15496098
TI  - Synthesis of the tubuvaline-tubuphenylalanine (Tuv-Tup) fragment of tubulysin.
AB  - [structure: see text] Advanced intermediates and analogues of tubulysins were
      prepared in a convergent strategy.

PMID- 15496099
TI  - Synthesis of polysubstituted 4-fluoroquinolinones.
AB  - [reaction: see text] A convenient one-pot synthesis of 4-fluoroquinolinones that
      are active against KDR kinase is described. The mechanism of the reaction is
      believed to involve the formation of a quinone methide intermediate.

PMID- 15496100
TI  - Enzymatic synthesis of a ring-contracted analogue of 5-enolpyruvylshikimate-3
      phosphate.
AB  - [reaction: see text] Three ring-contracted mimics of shikimate-3-phosphate,
      formed from the triols by shikimate kinase, were evaluated as substrates of the
      next enzyme in the pathway, EPSP synthase. The cyclopentylidene analogue (+)-2P
      was converted enzymatically to the enolpyruvyl derivative, thus demonstrating the
      second step of an artificial biosynthetic sequence.

PMID- 15496101
TI  - Practical synthesis of 1-aryl-6-(hydroxymethyl)-2-ketopiperazines via a 6-exo
      amide-epoxide cyclization.
AB  - [reaction: see text] Chiral 1-aryl-6-(hydroxymethyl)-2-ketopiperazines can be
      prepared via an operationally simple, 6-exo epoxide ring-opening cyclization to
      form the ketopiperazine C6-N1 bond in high yields and with excellent enantiomeric
      purity.

PMID- 15496102
TI  - Electronically promoted Payne rearrangement of 3-CF3-2,3-epoxyalcohols.
AB  - [reaction: see text] Smooth and selective Payne rearrangement was achieved for
      the above types of epoxyalcohols with a CF(3) group so as to form
      thermodynamically more stable alkoxides, where the strongly electron-withdrawing
      nature of this moiety played a significantly important role and was proved to
      overcome increased steric instability of epoxides from syn-E to anti-Z isomers.

PMID- 15496103
TI  - Efficient synthesis of alpha-C-galactosyl ceramide immunostimulants: use of
      ethylene-promoted olefin cross-metathesis.
AB  - [reaction: see text] Olefin cross-metathesis has been used to prepare alpha-C
      galactosylceramide derivatives. The metathesis process merged vinyl and propenyl
      glycosides with vinyl derivatives of phytosphingosine. The use of ethylene
      enhanced the yield of the methathesis step.

PMID- 15496104
TI  - Kinetic evidence for remote pi-aryl participation in the BF3-catalyzed
      rearrangement of [2 + 2] photocycloadducts of diarylhomobenzoquinones with
      diphenylacetylene.
AB  - [reaction: see text] The BF(3)-catalyzed rearrangement of cyclobutene-fused m-
      and p-substituted diarylhomobenzoquinones exclusively gave the keto-alcohols via
      a Wagner-Meerwein vinyl-anion migration followed by the annulation of a delta
      located endo-aryl group. The Hammett treatments for the endo/exo substituent
      effects, as well as the kinetic solvent effects, indicated that this reaction
      proceeds through the concerted S(N)2-like mechanism involving a rate-determining
      endo-aryl-assisted transition state.

PMID- 15496105
TI  - Water enables direct use of allyl alcohol for Tsuji-Trost reaction without
      activators.
AB  - [reaction: see text] An aqueous biphasic reaction system enables the direct use
      of allyl alcohol in the Tsuji-Trost reaction without the help of any activating
      reagents for allyl alcohol. The reaction conditions are neutral to basic,
      allowing the use of amines as the nucleophile. Theoretical calculations have
      elucidated the importance of hydration of the hydroxy group for the smooth
      generation of pi-allylpalladium species.

PMID- 15496107
TI  - Rapid construction of multisubstituted olefin structures using vinylboronate
      ester platform leading to highly fluorescent materials.
AB  - [reaction: see text] A catalytic one-pot triarylation on the C=C core of
      vinylboronate pinacol ester (1) produces extended pi-systems based on a
      multisubstituted olefin structure very rapidly. We established an efficient
      protocol for the Pd-catalyzed double C-H arylation of 1 with aryl halides, which
      was successfully integrated with C-B arylation with aryl halides (cross-coupling)
      in one pot. By using this method, several highly fluorescent materials with a
      wide range of color variations (blue to red) were discovered.

PMID- 15496106
TI  - Solid-phase combinatorial synthesis of peptide-biphenyl hybrids as calpain
      inhibitors.
AB  - [structure: see text] The combinatorial parallel synthesis of peptide-biphenyl
      hybrids on solid support using state of the art of peptide synthesis is reported.
      Key steps were the N to C addition of an amino moiety, hydrolysis of the methyl
      ester, and the absence of cross-linked compounds when the 2,2'-diamino-1,1'
      biphenyl was incorporated. When tested for activity as calpain inhibitors, some
      of the compounds exhibited IC(50) values in the nanomolar range.

PMID- 15496108
TI  - A new class of substituted aryl bis(oxazoline) ligands for highly
      enantioselective copper-catalyzed asymmetric aldol addition of dienolsilane to
      pyruvate and glyoxylate esters.
AB  - [reaction: see text] A new class of bis(oxazoline) ligands are introduced that
      feature o-alkoxyaryl substituents and provide the highest enantioselectivities
      yet reported for the copper-catalyzed asymmetric dienosilane aldol addition to
      pyruvate and glyoxylate esters. Enantioselectivities up to 98% ee (before
      recrystallization) and isolated yields up to 91% were observed. Additionally,
      chloride counterions were found to be superior to triflate for this reaction.

PMID- 15496109
TI  - MPC1001 and its analogues: new antitumor agents from the fungus Cladorrhinum
      species.
AB  - [structure: see text] Eight new compounds, MPC1001 and MPC1001B-H, were isolated
      from the fungus Cladorrhinum sp. KY4922. Multiple NMR experiments and CD data
      revealed MPC1001 to be an O-methyl derivative of emestrin, a 15-membered
      antifungal antibiotic containing a unique epidithiodioxopiperazine skeleton.
      Other compounds were elucidated to be structurally related novel analogues.
      MPC1001 and the analogues exerted potent antiproliferative activities against a
      human tumor cell line.

PMID- 15496110
TI  - Asymmetric hydrogenation of ketones using a ruthenium(II) catalyst containing
      BINOL-derived monodonor phosphorus-donor ligands.
AB  - [structure: see text] A series of ruthenium(II) complexes containing BINOL-based
      monodonor phosphorus ligands have been prepared and applied to the asymmetric
      catalysis of the hydrogenation of aryl/alkyl ketones. The best ligands for this
      application are those which contain an aromatic groups with either a methoxide or
      bromide on the ortho position. Using these ligands, alcohols with ee's of up to
      99% are formed.

PMID- 15496111
TI  - Notable coordination effects of 2-pyridinesulfonamides leading to efficient
      aziridination and selective aziridine ring opening.
AB  - [reaction: see text] We have developed, on the basis of a chelation-strategy, an
      efficient copper-catalyzed aziridination protocol with the use of 5-methyl-2
      pyridinesulfonamide and PhI(OAc)(2). The reaction proceeds smoothly under mild
      conditions to give aziridines in moderate to good yields in the absence of
      external ligands or bases. The coordination-assisted approach offers the
      additional benefits that efficient deprotection of the N-substituent and
      selective aziridine ring-opening are effectively achieved.

PMID- 15496112
TI  - Asymmetric allylic alkylation of ketone enolates: an asymmetric Claisen
      surrogate.
AB  - [reaction: see text] The combination of catalytic palladium(0) and Trost ligand
      provides an effective catalyst for the rearrangement of allyl beta-ketoesters.
      The mechanism of the transformation involves formation of pi-allyl palladium
      intermediates which undergo enantioselective attack by ketone enolates.
      Decarboxylation of beta-ketocarboxylates allows regiospecific generation of
      enolates under extremely mild conditions.

PMID- 15496113
TI  - Enantioselective Cu-catalyzed conjugate addition of diethylzinc to acyclic
      aliphatic enones.
AB  - [reaction: see text] A new P-chiral phosphine bis(sulfonamide) ligand has been
      developed that allows the Cu-catalyzed enantioselective conjugate addition of
      Et(2)Zn to acyclic aliphatic enones. The reactions proceed with excellent levels
      of enantioselectivity (90-95% ee) with a range of enone substrates, involve the
      use of only 1.2 equiv of Et(2)Zn, and give best results at ambient temperature.

PMID- 15496114
TI  - Gold catalysis in organic synthesis: efficient cycloisomerization of alpha
      aminoallenes to 3-pyrrolines.
AB  - [reaction: see text] The gold(III) chloride-catalyzed cycloisomerization of
      various alpha-aminoallenes gave the corresponding 3-pyrrolines in good to high
      chemical yields. An interesting dependence of the chirality transfer and
      reactivity on the N-protecting group was observed. The 3-pyrrolines are highly
      useful intermediates for the synthesis of functionalized pyrrolines,
      pyrrolidines, and other natural products.

PMID- 15496115
TI  - A unified approach to quinolizinium cations and related systems by ring-closing
      metathesis.
AB  - [reaction: see text] The first example of an olefin ring-closing metathesis
      reaction on cationic heteroaromatic systems is described. Dihydroquinolizinium
      cations and a variety of related cationic systems are synthesized in an efficient
      approach from N-alkenyl alpha-vinyl azinium salts using Grubbs' catalysts.

PMID- 15496116
TI  - The first regioselective palladium-catalyzed indolization of 2-bromo- or 2
      chloroanilines with internal alkynes: a new approach to 2,3-disubstituted
      indoles.
AB  - [reaction: see text] The first practical and economical process for synthesis of
      2,3-disubstituted indole compounds has been developed with high regioselectivity
      by palladium-catalyzed indolization of 2-bromo- or chloroanilines and their
      derivatives with internal alkynes.

PMID- 15496117
TI  - Efficient and simple NaBH4 reduction of esters at cationic micellar surface.
AB  - [reaction: see text] A simple, efficacious, and biocompatible methodology for
      reducing esters with sodium borohydride at an aqueous cationic micellar surface
      under ambient conditions has been developed. The present method holds promise for
      future use in selective functional group reduction and stereocontrolled alcohol
      synthesis.

PMID- 15496119
TI  - Usefulness of optical brightners in medical mycology.

PMID- 15496120
TI  - [Colorimetric methods for in vitro antifungal susceptibility testing].

PMID- 15496121
TI  - Hospital sources of Aspergillus: New routes of transmission?
AB  - With the continuing increase in the number of severely immunocompromised
      patients, hospitals are faced with the growing problem of invasive aspergillosis
      and other opportunistic fungal infections. Since treatment of these infections
      are difficult and outcome is often fatal, preventive measures are of major
      importance in the control of invasive filamentous fungal infections. Until
      recently, inhalation of airborne conidia was believed to be the primary route of
      acquiring Aspergillus infection. Despite the fact, that efforts to filter the
      hospital air has led to a reduction of airborne conidia paralleled by a decrease
      in the frequency of invasive infections, the correlation between the
      concentration of Aspergillus conidia in hospital air and the risk of invasive
      infections remains unclear. Furthermore, alternative modes of transmission may
      exist and should be recognized and investigated. The discovery of hospital water
      as a potential source of Aspergillus fumigatus and other filamentous fungi may
      suggest a new route for the transmission of invasive filamentous fungal
      infections. Epidemiological studies, based on molecular characterization and
      comparisons of fungal isolates recovered from patients and environment, are
      needed to expand our understanding of these alternative routes of transmission.

PMID- 15496122
TI  - Characteristics of biofilm formation by Candida albicans.
AB  - A variety of manifestations of Candida albicans infections are associated with
      the formation of biofilms on the surface of biomaterials. Cells in biofilms
      display phenotypic traits that are dramatically different from their free
      floating planktonic counterparts, such as increased resistance to anti-microbial
      agents and protection form host defenses. Here, we describe the characteristics
      of C. albicans biofilm development using a 96 well microtitre plate model,
      microscopic observations and a colorimetric method based on the use of a modified
      tetrazolium salt (2,3-bis(2-methoxy-4-nitro-5-sulfo-phenyl)-2H-tetrazolium-5
      carboxanilide, XTT) to monitor metabolic activities of cells within the biofilm.
      C. albicans biofilm formation was characterized by initial adherence of yeast
      cells (0-2 h), followed by germination and micro-colony formation (2-4 h),
      filamentation (4-6 h), monolayer development (6-8 h), proliferation (8-24 h) and
      maturation (24-48 h). The XTT-reduction assay showed a linear relationship
      between cellular density of the biofilm and metabolic activity. Serum and saliva
      pre-conditioning films increased the initial attachment of C. albicans, but had
      minimal effect on subsequent biofilm formation. Scanning electron microscopy and
      confocal scanning laser microscopy were used to visualize C. albicans biofilms.
      Mature C. albicans biofilms consisted of a dense network of yeasts cells and
      hyphal elements embedded within exopolymeric material. C. albicans biofilms
      displayed a complex three dimensional structure which demonstrated spatial
      heterogeneity and a typical architecture showing microcolonies with ramifying
      water channels. Antifungal susceptibility testing demonstrated the increased
      resistance of sessile C. albicans cells against clinically used fluconazole and
      amphotericin B as compared to their planktonic counterparts.

PMID- 15496123
TI  - Effect of contraceptives on the prevalence of vaginal colonization with Candida
      species in Edo State, Nigeria.
AB  - High vaginal swabs (HVS) obtained from 500 volunteers in Edo State, Nigeria which
      comprised 394 contraceptive users and 106 non-contraceptive users were screened
      for the prevalence of Candida species using standard procedures. Results revealed
      the isolation of Candida species in 246 of volunteers. These included Candida
      albicans 174 (38.4%), Candida pseudotropicalis 20 (4%), Candida stellatoidea 15
      (3%), Candida krusei nine (1.8%), Candida guilliermondii 12 (2.4%), Candida
      tropicalis 11 (2.2%) and Candida glabrata five (1%). Of the 394 contraceptive
      users, 203 (51.5%) had Candida species isolated from them compared to 43 (40.6%)
      from 106 non-contraceptive users. There was significant relationship (P<0.001)
      between the type of contraceptive used and the prevalence of vaginal
      colonization. Age and marital status of the volunteers sampled had significant
      relationship (P<0.001) with the prevalence of vaginal colonization. Results have
      revealed an association between use of contraceptive and the prevalence of
      vaginal colonization in our environment.

PMID- 15496124
TI  - Chromosome length polymorphism in Cryptococcus neoformans clinical and
      environmental isolates.
AB  - A protocol for intact DNA preparation from the basidiomycetous yeast Cryptococcus
      neoformans has been developed and applied to karyotyping C. neoformans isolates
      displaying different degrees of capsule formation. A total of 46 strains have
      been analyzed: 23 (50%) isolated from environmental samples (pigeon droppings),
      all of them belonging to C. neoformans var. neoformans; and 23 (50%) from
      clinical samples (human and veterinarian) including 10 isolates of C. neoformans
      var. neoformans and 13 isolates of C. neoformans var. gattii. Our results showed
      a global genome size ranging from 14.2 to 20.9 Mb for variety neoformans and from
      7.9 to 16.8 Mb for variety gattii. The karyotype diversity was very high for
      variety neoformans (29 different patterns for the 33 analyzed strains) and lower
      for variety gattii (six different patterns for 13 strains). No grouping among
      variety neoformans strains from the same origin was found indicating very high
      genome diversity for this variety, irrespectively of the origin of the strains.

PMID- 15496125
TI  - Histoplasma capsulatum isolated from Didelphis albiventris (Marsupialia:
      Didelphidae) in the State of Minas Gerais, Brazil.
AB  - We report the isolation of Histoplasma capsulatum from a culture of the viscera
      of Didelphis albiventris, one of the marsupial species found in Brazil. To our
      knowledge, this is the first report of the isolation of this fungus from this
      mammalian species. This finding confirms the ubiquitous presence of H. capsulatum
      in nature.

PMID- 15496126
TI  - [Toxic activity of Penicillium citrinum metabolites on Mus musculus mice].
AB  - The aims of this work were to study the influence of secondary metabolites
      produced by a Penicillium citrinum strain. Mus musculus mice were fed with a diet
      containing those metabolites to determine both its influence on their development
      and the pathological and biochemical changes on experimental animals. Male and
      female including pregnant females, were studied. One group received commercial
      feed (A.B.) to which the citrinin- producing mould had been added (LF), another
      received A.B. contaminated with commercial citrinin (LC). The last group received
      noncontaminated feed (LT). The animals were weighed weekly, and sacrificed after
      sixty days, so that they could be studied both macro and microscopically. In LF
      and LT mice, haematological analysis was carried out and hemosiderin was looked
      for in urine. The diet of the newborne mice, after weaning, was identical to that
      of their parent. The treated animals (LF and LC) showed morphological
      alterations, a significant decrease in weight and morphologic alterations and
      hemosiderin granules were detected in some of their organs. In LT all breeds
      survived, none of the mice showed neither macro nor microscopic anomalies and had
      normal biochemical parameters. Fewer breeds in LF survived, male infertility was
      detected and some of their haematologic parameters were also measurably lower.

PMID- 15496127
TI  - [Efficacy of the APimicos-B to control and prevent chalkbrood disease in honey
      bees].
AB  - Chalkbrood disease in Apis mellifera is a fungal disease affecting developing
      brood, infested larvae become mummified. As it is a factorial disease, studies on
      this pathology are obstructed by the need of some predisposing conditions which
      must occur for such disease to develop. Thus, many questions are yet to be
      answered about which treatments to apply. The aim of this work is to evaluate the
      efficacy of the Apimicos-B, a treatment against chalk brood. To induce the
      disease, some pieces of combs containing susceptible worker brood both from
      infected and treated colonies and from infected and untreated colonies were
      cooled. No significant differences were registered (53.12% and 59.58% of
      mummification respectively).

PMID- 15496128
TI  - Viability, morphological characteristics and dimorphic ability of fungi preserved
      by different methods.
AB  - The viability, morphological characteristics and dimorphic ability of fungi were
      evaluated. Strain subcultures were maintained under mineral oil and in soil for
      different periods of time, ranging from 49 to eight years. Of the 16 Blastomyces
      dermatitidis strains, four maintained viability and were able to complete the
      dimorphic process to the M phase producing a large amount of conidia, but were
      unable to form Y cells at 36 degrees C. Of the 15 Histoplasma capsulatum var.
      capsulatum strains, only one was viable but it was impossible to check its
      identity because it lost sporulating and dimorphic ability. Of the 53 Sporothrix
      schenckii strains, 37 were viable, 28 able to sporulate and 12 of them completed
      the whole M <=> Y dimorphic process. All subcultures in soil became inviable. The
      results demonstrate that the preservation methods used here affected the
      morphology and sporulating and dimorphic ability of the strains. B. dermatitidis
      and S. schenckii were considered to be species that survive better than H.
      capsulatum var. capsulatum under mineral oil. Thus, it is necessary to establish
      routine monitoring and appropriate environmental and culture conditions, using
      less widely spaced transplants and choosing the exact time of intervention to
      induce growth and development restriction in each strain.

PMID- 15496129
TI  - [Identification of Candida albicans using the chromogenic medium Albicans ID].
AB  - The correct identification of the microrganism is the base for epidemiological
      studies and treatment of infections. The aim of our study was to evaluate the
      efficacy of the chromogenic media Albicans ID (bioMerieux, France) in the
      identification of Candida albicans. A total of 190 yeasts strains were evaluated
      in the study. A rate of 100% of all C. albicans (80) and Candida dubliniensis
      (five) strains exhibited blue color. Nevertheless, the blue color was also
      observed with cultures of Candida rugosa (3/5) and Candida tropicalis (3/17).
      Albicans ID cromogenic media presented specificity rate of 90% and positive and
      negative predictive values of 88% and 100%, respectively, in the identification
      of C. albicans.

PMID- 15496130
TI  - Cutaneous cryptococcosis due to Cryptococcus neoformans var. gattii.
AB  - A case of cutaneous cryptococcosis due to Cryptococcus neoformans var. gattii in
      an immunocompetent host is presented. In addition a review of the literature on
      this subject was carried out and a brief comment made on occurrence of the
      variety gattii in Brazil.

PMID- 15496131
TI  - Glacial influences on solar radiation in a subarctic sea.
AB  - Understanding macroscale processes controlling solar radiation in marine systems
      will be important in interpreting the potential effects of global change from
      increasing ultraviolet radiation (UV) and glacial retreat. This study provides
      the first quantitative assessment of UV in the water column of Prince William
      Sound, a subarctic, semienclosed sea surrounded by mountains, glaciers, rivers,
      bays and fjords in south central Alaska. Glacial influences on diffuse
      attenuation coefficients (Kd) were determined along an approximate 120 km
      transect running NE (61 degrees 07'43''N, 146 degrees 17'1''W) to SW (60 degrees
      27'25''N, 148 degrees 05'27'' W). Glacial meltwater and flour caused a 10-fold
      increase in Kd for visible light, UV-A and UV-B, whereas high optical clarity was
      present in a diversity of areas away from glacial influences. Transition areas
      and locations affected by calving of a tidewater glacier had intermediate Kd
      values. Depths at 99% attenuation ranged from less than 0.2 m near glacial
      streams to greater than 5 m in bays and open ocean distant from sources of
      glacial sediments. These results suggest that potential global change from
      increasing UV and glacial retreat may have heterogeneous effects on subarctic
      marine systems.

PMID- 15496132
TI  - Ultraviolet wavelength dependence of photomorphological and photosynthetic
      responses in Brassica napus and Arabidopsis thaliana.
AB  - Among the photomorphological responses in plants induced by ultraviolet-B
      radiation (UVB; 290 nm-320 nm) are leaf asymmetry, leaf thickening and cotyledon
      curling. We constructed an action spectrum of cotyledon curling in light-grown
      Brassica napus to characterize the UVB photoreceptor that initiates this
      response. Cotyledon curling was also characterized in Arabidopsis thaliana. Peak
      efficiency for this response occurred between 285 and 290 nm. Additionally, UVB
      induced changes in epidermal cells from A. thaliana cotyledons were assessed
      because they are the likely site of UVB photoreception that leads to curling.
      Investigation of cellular structure, chlorophyll a fluorescence and chlorophyll
      concentration indicated that cotyledon curling is not concomitant with gross
      cellular damage or inhibition of photosynthesis, which only occurred in response
      to wavelengths <280 nm. Many UVB effects are apparently an indirect consequence
      of UVB radiation, dependent on UVB-mediated increases in reactive oxygen species
      (ROS) that either act as a signal in the UVB transduction pathway or cause
      oxidative damage. The cotyledon curling response was impeded by ascorbate and
      cystine, ROS scavengers and was promoted by H(2)O(2), a ROS. We suggest that
      following absorption by a UVB chromophore, ROS are generated via
      photosensitization, ultimately leading to cotyledon curling.

PMID- 15496133
TI  - Phototropins and associated signaling: providing the power of movement in higher
      plants.
AB  - Recent developments in phototropin biology have provided exciting new findings on
      the roles of these photoreceptor proteins in plants. Much of the recent work has
      focused on phototropin photochemistry and the structural alterations in both the
      chromophoric and peptide components of the molecule associated with light
      perception. In this review, specific aspects of phototropin action in higher
      plants will be discussed in the context of these new findings. Although, as their
      name suggests, phototropins play a key role in phototropic responses in plants,
      increasing evidence shows they have many other functions in plants. In this
      review, the roles of phototropins in additional plant "movement" responses will
      be addressed; in particular their roles in stomatal aperture control and
      chloroplast movements. In discussing these various movement responses special
      attention will be given to identified and hypothesized downstream signaling
      partners or events that enable the phototropins to selectively participate in any
      one or more of these responses in a given light condition.

PMID- 15496134
TI  - Photobiology of ocular melanocytes and melanoma.
AB  - There are two different types of ocular melanocytes and melanomas. Conjunctival
      melanocytes are located on the surface of the eye and are exposed to visible
      light and UV radiation. Recently, epidemiological studies demonstrated that
      sunlight plays a definite role in the occurrence of conjunctival melanoma, as it
      does in cutaneous melanoma. Uveal melanocytes consist of the iridal melanocytes,
      which are exposed to visible light and UV radiation; and the ciliary body
      melanocytes and choroidal melanocytes, which are not exposed to light radiation.
      Epidemiological studies demonstrated that sunlight may play a role in the
      occurrence of iridal melanoma, but may not be a major factor in the etiology of
      ciliary body and choroidal melanomas. Uveal melanocytes differ from epidermal
      melanocytes in that epidermal melanocytes respond to UV radiation and skin color
      becomes darker after exposure to sunlight; but uveal melanocytes do not respond
      to UV radiation and the iris color remains stable after exposure to sunlight.
      Recently, in vitro studies indicate that this phenomenon is determined both by
      cellular factors and environmental factors.

PMID- 15496135
TI  - Inverse relationship between increased apoptosis and decreased skin cancer in UV
      irradiated CD1d-/- mice.
AB  - We previously demonstrated that CD1d knockout mice were resistant to ultraviolet
      (UV)-induced immunosuppression. Because immune suppression is a critical factor
      in the development of UV-induced skin cancers, we investigated the response of
      wild type (WT) and CD1d-/- mice to UV carcinogenesis. We found that although 100%
      of WT mice developed skin tumors after 45 weeks of UV irradiation, only 60% of
      CD1d-/- mice developed skin tumors. To investigate the mechanisms involved in the
      resistance of CD1d-/- mice to UV-induced carcinogenesis, we determined the time
      course and kinetics of keratinocyte cell death after UV irradiation. After acute
      UV exposure, the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick
      end-labeling (TUNEL)-positive keratinocytes were eliminated from the skin of WT
      mice by 72 h post-UV, but they still persisted until 96 h in CD1d-/- mice. The
      kinetics of p53 protein expression closely followed the kinetics of apoptotic
      cell death. Chronic UV irradiation resulted in induction of a significantly
      higher number of apoptotic keratinocytes in CD1d-/- than WT mice. In addition,
      epidermis and dermis from chronically UV-irradiated CD1d-/- mice harbored
      significantly fewer p53 mutations than WT mice. These results indicate that the
      resistance of CD1d-/- mice to UV carcinogenesis may be due to increased cell
      death and elimination of keratinocytes and fibroblasts containing DNA damage and
      p53 mutations.

PMID- 15496137
TI  - Thyroid hormones directly activate the expression of the human and mouse
      uncoupling protein-3 genes through a thyroid response element in the proximal
      promoter region.
AB  - The transcription of the human UCP3 (uncoupling protein-3) gene in skeletal
      muscle is tightly regulated by metabolic signals related to fatty acid
      availability. However, changes in thyroid status also modulate UCP3 gene
      expression, albeit by unknown mechanisms. We created transgenic mice bearing the
      entire human UCP3 gene to investigate the effect of thyroid hormones on human
      UCP3 gene expression. Treatment of human UCP3 transgenic mice with thyroid
      hormones induced the expression of the human gene in skeletal muscle. In
      addition, transient transfection experiments demonstrate that thyroid hormones
      activate the transcription of the human UCP3 gene promoter when MyoD and the TR
      (thyroid hormone receptor) were co-transfected. The action of thyroid hormones on
      UCP3 gene transcription is mediated by the binding of the TR to a proximal region
      in the UCP3 gene promoter that contains a direct repeat structure. An intact DNA
      sequence of this site is required for thyroid hormone responsiveness and TR
      binding. Chromatin immunoprecipitation assays revealed that the TR binds this
      element in vivo. The murine Ucp3 gene promoter was also dependent on MyoD and
      responsive to thyroid hormone in transient transfection assays. However, it was
      much less sensitive to thyroid hormone than the human UCP3 promoter. In summary,
      UCP3 gene transcription is activated by thyroid hormone treatment in vivo, and
      this activation is mediated by a TRE (thyroid hormone response element) in the
      proximal promoter region. Such regulation suggests a link between UCP3 gene
      expression and the effects of thyroid hormone on mitochondrial function in
      skeletal muscle.

PMID- 15496138
TI  - Rho GTPases and leucocyte-induced endothelial remodelling.
AB  - Leucocytes in the bloodstream respond rapidly to inflammatory signals by crossing
      the blood vessel wall and entering the tissues. This process involves adhesion
      to, and subsequent transmigration across, the endothelium, mediated by a cascade
      of interactions between adhesion molecules and stimulation of intracellular
      signalling pathways in both leucocytes and endothelial cells. This leads to
      changes in endothelial cell morphology that assist leucocyte extravasation,
      including endothelial cell contraction, intercellular junction disruption,
      increased permeability, remodelling of the endothelial apical surface and
      alterations in vesicle trafficking. Rho GTPases play a central role in many of
      the endothelial responses to leucocyte interaction. In this review, we discuss
      recent findings on leucocyte-induced alterations to endothelial cells, and the
      roles of Rho GTPases in these responses.

PMID- 15496139
TI  - Porphyrin-substrate binding to murine ferrochelatase: effect on the thermal
      stability of the enzyme.
AB  - Ferrochelatase (EC 4.99.1.1), the terminal enzyme of the haem biosynthetic
      pathway, catalyses the chelation of Fe(II) into the protoporphyrin IX ring. The
      energetics of the binding between murine ferrochelatase and mesoporphyrin were
      determined using isothermal titration calorimetry, which revealed a stoichiometry
      of one molecule of mesoporphyrin bound per protein monomer. The binding is
      strongly exothermic, with a large intrinsic enthalpy (DeltaH=-97.1 kJ x mol(-1)),
      and is associated with the uptake of two protons from the buffer. This proton
      transfer suggests that hydrogen bonding between ferrochelatase and mesoporphyrin
      is a key factor in the thermodynamics of the binding reaction. Differential
      scanning calorimetry thermograms indicated a co-operative two-state denaturation
      process with a single transition temperature of 56 degrees C for wild-type murine
      ferrochelatase. An increase in the thermal stability of ferrochelatase is
      dependent upon mesoporphyrin binding. Similarly, murine ferrochelatase variants,
      in which the active site Glu-289 was replaced by either glutamine or alanine and,
      when purified, contained specifically-bound protoporphyrin, exhibited enhanced
      protein stability when compared with wild-type ferrochelatase. However, in
      contrast with the wild-type enzyme, the thermal denaturation of ferrochelatase
      variants was best described as a non-co-operative denaturation process.

PMID- 15496140
TI  - Co-expression of glutaminase K and L isoenzymes in human tumour cells.
AB  - The pattern of expression of glutaminase isoenzymes in tumour cells has been
      investigated to clarify its role in the malignant transformation and the prospect
      of its use as a clinically relevant factor. Using leukaemia cells from medullar
      blood of human patients and several established human cancer cell lines, we have
      developed a competitive RT (reverse transcriptase)-PCR assay to quantify
      simultaneously K-type (kidney-type) and L-type (liver-type) glutaminase mRNAs. Co
      expression of both transcripts and higher amounts of L-type mRNA were always
      found in all cancer cell types analysed. However, mature lymphocytes from the
      medullar blood of a patient suffering aplasia did not express the K-type
      transcript and showed a 15-fold increase of L-type transcript. Co-expression was
      also confirmed at the protein level using isoform-specific antibodies;
      nevertheless, it did not correlate with the relative abundance of glutaminase
      transcripts and strong K-type protein signals were detected. On the other hand,
      marked differences were found with regard to glutamate inhibition and phosphate
      activation of tumour glutaminase activity. Taken together, the protein data
      suggest that K isoform would account for the majority of glutaminase activity in
      these human tumour cells. The results confirm that simultaneous expression of
      both isoenzymes in human cancer cells is a more frequent event than previously
      thought. Furthermore, the present work and other previous data suggest that K
      isoform is up-regulated with increased rates of proliferation, whereas prevalence
      of the L isoform seems to be related with resting or quiescent cell states.

PMID- 15496141
TI  - NEDD4-2 (neural precursor cell expressed, developmentally down-regulated 4-2)
      negatively regulates TGF-beta (transforming growth factor-beta) signalling by
      inducing ubiquitin-mediated degradation of Smad2 and TGF-beta type I receptor.
AB  - Inhibitory Smad, Smad7, is a potent inhibitor of TGF-beta (transforming growth
      factor-beta) superfamily signalling. By binding to activated type I receptors, it
      prevents the activation of R-Smads (receptor-regulated Smads). To identify new
      components of the Smad pathway, we performed yeast two-hybrid screening using
      Smad7 as bait, and identified NEDD4-2 (neural precursor cell expressed,
      developmentally down-regulated 4-2) as a direct binding partner of Smad7. NEDD4-2
      is structurally similar to Smurfs (Smad ubiquitin regulatory factors) 1 and 2,
      which were identified previously as E3 ubiquitin ligases for R-Smads and TGF-beta
      superfamily receptors. NEDD4-2 functions like Smurfs 1 and 2 in that it
      associates with TGF-beta type I receptor via Smad7, and induces its ubiquitin
      dependent degradation. Moreover, NEDD4-2 bound to TGF-beta-specific R-Smads,
      Smads 2 and 3, in a ligand-dependent manner, and induced degradation of Smad2,
      but not Smad3. However, in contrast with Smurf2, NEDD4-2 failed to induce
      ubiquitination of SnoN (Ski-related novel protein N), although NEDD4-2 bound to
      SnoN via Smad2 more strongly than Smurf2. We showed further that overexpressed
      NEDD4-2 prevents transcriptional activity induced by TGF-beta and BMP, whereas
      silencing of the NEDD4-2 gene by siRNA (small interfering RNA) resulted in
      enhancement of the responsiveness to TGF-beta superfamily cytokines. These data
      suggest that NEDD4-2 is a member of the Smurf-like C2-WW-HECT (WW is Trp-Trp and
      HECT is homologous to the E6-accessory protein) type E3 ubiquitin ligases, which
      negatively regulate TGF-beta superfamily signalling through similar, but not
      identical, mechanisms to those used by Smurfs.

PMID- 15496142
TI  - Identification and characterization of the human ARD1-NATH protein
      acetyltransferase complex.
AB  - Protein acetyltransferases and deacetylases have been implicated in oncogenesis,
      apoptosis and cell cycle regulation. Most of the protein acetyltransferases
      described acetylate epsilon-amino groups of lysine residues within proteins.
      Mouse ARD1 (homologue of yeast Ard1p, where Ard1p stands for arrest defective 1
      protein) is the only known protein acetyltransferase catalysing acetylation of
      proteins at both alpha-(N-terminus) and epsilon-amino groups. Yeast Ard1p
      interacts with Nat1p (N-acetyltransferase 1 protein) to form a functional NAT (N
      acetyltransferase). We now describe the human homologue of Nat1p, NATH (NAT
      human), as the partner of the hARD1 (human ARD1) protein. Included in the
      characterization of the NATH and hARD1 proteins is the following: (i) endogenous
      NATH and hARD1 proteins are expressed in human epithelial, glioma and
      promyelocytic cell lines; (ii) NATH and hARD1 form a stable complex, as
      investigated by reciprocal immunoprecipitations followed by MS analysis; (iii)
      NATH-hARD1 complex expresses N-terminal acetylation activity; (iv) NATH and hARD1
      interact with ribosomal subunits, indicating a co-translational acetyltransferase
      function; (v) NATH is localized in the cytoplasm, whereas hARD1 localizes both to
      the cytoplasm and nucleus; (vi) hARD1 partially co-localizes in nuclear spots
      with the transcription factor HIF-1alpha (hypoxia-inducible factor 1alpha), a
      known epsilon-amino substrate of ARD1; (vii) NATH and hARD1 are cleaved during
      apoptosis, resulting in a decreased NAT activity. This study identifies the human
      homologues of the yeast Ard1p and Nat1p proteins and presents new aspects of the
      NATH and hARD1 proteins relative to their yeast homologues.

PMID- 15496143
TI  - Induction of human spermine oxidase SMO(PAOh1) is regulated at the levels of new
      mRNA synthesis, mRNA stabilization and newly synthesized protein.
AB  - The oxidation of polyamines induced by antitumour polyamine analogues has been
      associated with tumour response to specific agents. The human spermine oxidase,
      SMO(PAOh1), is one enzyme that may play a direct role in the cellular response to
      the antitumour polyamine analogues. In the present study, the induction of
      SMO(PAOh1) enzyme activity by CPENSpm [N1-ethyl-N11-(cyclopropyl)methyl
      4,8,diazaundecane] is demonstrated to be a result of newly synthesized mRNA and
      protein. Inhibition of new RNA synthesis by actinomycin D inhibits both the
      appearance of SMO(PAOh1) mRNA and enzyme activity. Similarly, inhibition of newly
      synthesized protein with cycloheximide prevents analogue-induced enzyme activity.
      Half-life determinations indicate that stabilization of SMO(PAOh1) protein does
      not play a significant role in analogue-induced activity. However, half-life
      experiments using actinomycin D indicate that CPENSpm treatment not only
      increases mRNA expression, but also leads to a significant increase in mRNA half
      life (17.1 and 8.8 h for CPENSpm-treated cells and control respectively). Using
      reporter constructs encompassing the SMO(PAOh1) promoter region, a 30-90%
      increase in transcription is observed after exposure to CPENSpm. The present
      results are consistent with the hypothesis that analogue-induced expression of
      SMO(PAOh1) is a result of increased transcription and stabilization of SMO(PAOh1)
      mRNA, leading to increased protein production and enzyme activity. These data
      indicate that the major level of control of SMO(PAOh1) expression in response to
      polyamine analogues exposure is at the level of mRNA.

PMID- 15496144
TI  - Acceptance and rejection: cost-effectiveness and the working nephrologist.
AB  - While many nephrologists have developed a sophisticated approach to appraising
      clinical trials, an equal comfort in critiquing cost-effectiveness literature is
      often lagging. Readers can wonder how new results compare to those from other
      cost-effectiveness trials, and whether they should accept a new intervention as
      cost-effective or reject it as too costly for the benefit it produces. Critical
      readers should first judge whether the authors have made the correct trade-off
      between complexity and generalizability when selecting a study perspective, and
      should examine the method of linkage between costs and effectiveness. The most
      popular method is the incremental cost-effectiveness ratio (ICER), which has
      limitations that have led some authors to prefer the net monetary benefit (NMB),
      where confidence intervals are more easily determined and which can more readily
      be used in regression analyses. Interpretation of the ICER and NMB require the
      choice of a cost-effectiveness ceiling, representing the maximum that society
      would be willing to pay for an incremental health benefit, and the development of
      a decision rule based on this maximum. Comparing cost-effectiveness studies from
      different disciplines requires the use of "universal" effectiveness measures,
      such as the quality-adjusted life-year (QALY). An understanding of study
      perspective, the relative strengths of different cost-effectiveness measures, the
      methods for measuring uncertainty in these estimates, and how to select and use
      cost-effectiveness ceiling ratios will help the critical reader to determine if a
      new intervention should be accepted or rejected.

PMID- 15496145
TI  - Regulatory and functional interaction of vasoactive factors in the kidney and
      extracellular pH.
AB  - A growing body of evidence suggests that vasoactive factors produced in the
      kidney such as nitric oxide, endothelins, angiotensin, and prostaglandins
      participate actively in the regulation of acid-base homeostasis under physiologic
      conditions. In addition, recent reports indicate that alterations in the systemic
      acid-base status may also influence the generation of vasoactive cytokines in the
      kidney, which in turn may mediate the renal effector processes that tend to
      restore normality under such conditions. Metabolic acidosis, which so frequently
      accompanies many forms of chronic renal failure (CRF), may contribute to down
      regulation of intrarenal nitric oxide production that characterizes CRF. Reduced
      extracellular pH inhibits inducible nitric oxide production in mesangial cells by
      altering the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH)
      oxidation, an important posttranslational mechanism in the inducible nitric oxide
      synthase (iNOS) activation. The underlying defects resulting in the uncoupling of
      NADPH oxidation in acidemic microenvironment are discussed. Acidosis stimulates
      renal production of endothelins, which mediate proximal tubular acidification by
      enhancing sodium-hydrogen exchanger-3 (NHE-3) activity. Renal endothelins mediate
      enhanced urinary acid excretion following dietary acid ingestion, an effect that
      is effectively blocked by endothelin receptor blockers. Reduced extracellular pH
      stimulates endothelin secretion from renal microvascular endothelial cells, which
      may promote enhanced acid excretion from the distal tubule under conditions of
      acidosis. These phenomena as well as the role of angiotensin and renal
      prostaglandins in mediating renal acidification in normal and acidotic conditions
      are discussed in this review, which describe the regulatory interaction between
      extracellular pH and renal vasoactive factors.

PMID- 15496146
TI  - Disease-causing missense mutations in NPHS2 gene alter normal nephrin trafficking
      to the plasma membrane.
AB  - BACKGROUND: Podocin is a membrane-integrated protein that is located at the
      glomerular slit diaphragm and directly interacts with nephrin. The gene encoding
      podocin, NPHS2, is mutated in patients with autosomal-recessive steroid-resistant
      nephrotic syndrome (SRN). In order to study a potential pathomechanism of massive
      proteinuria in patients with SRN, we have investigated the trafficking and
      subcellular localization of five common disease-causing missense mutants of human
      podocin. METHODS: Site-directed mutagenesis was applied to generate cDNA
      constructs encoding five different missense mutations of human podocin (P20L,
      G92C, R138Q, V180M, and R291W). To identify the subcellular localization of each
      mutant in transfected human embryonic kidney (HEK)293 cells, we have generated
      and characterized a rabbit polyclonal antibody against the human podocin.
      Specificity of the antibody was determined by light and immunoelectron
      microscopy, as well as immunoblot analysis using human glomeruli. Confocal
      microscopy was applied to determine subcellular localization of the wild-type and
      the mutated podocin molecules, as well as wild-type nephrin in transfected cells.
      Immunoprecipitation and pull-down studies were carried out to investigate the
      molecular interaction of podocin mutants and wild-type nephrin. RESULTS:
      Immunofluorescence and confocal microscopy showed that wild-type podocin located
      to the plasma membrane when expressed in HEK293 cells. Two missense mutations,
      P20L and G92C, located at the N-terminus part of the molecule, were also present
      at the plasma membrane, indicating that these mutations did not affect the
      subcellular localization of the mutated podocin molecules. In contrast,
      subcellular localization of three other missense mutants located in the proximal
      C-terminus part of the protein was drastically altered, in which R138Q was
      retained in the endoplasmic reticulum (ER), V180M formed inclusion bodies in the
      cytoplasm, and the R291W mutant was trapped both in the ER and in small
      intracellular vesicles. Interestingly, this abnormal subcellular localization of
      podocin missense mutants also resulted in alteration in protein trafficking of
      wild-type nephrin in cotransfected cells through the strong protein binding
      between both molecules. CONCLUSION: In patients with SRN, some missense mutations
      in the NPHS2 gene not only lead to misfolding and mislocalization of the mutated
      podocin, but they can also interfere with slit diaphragm structure and function
      by altering the proper trafficking of nephrin to the plasma membrane.

PMID- 15496147
TI  - Epidermal growth factor receptor tyrosine kinase inhibition is not protective in
      PCK rats.
AB  - BACKGROUND: Advances in the understanding of cystogenesis, identification of the
      PKHD1 gene and availability of a rat model (the PCK rat) caused by a Pkhd1
      mutation facilitate testing of therapies for autosomal-recessive polycystic
      kidney disease (ARPKD). Considerable support exists for the importance of the
      epidermal growth factor (EGF)/transforming growth factor-alpha (TGF-alpha)/EGF
      receptor (EGFR) axis and of the adenylyl cyclase-adenosine 3',5'-cyclic
      monophosphate (cAMP) pathway in the pathogenesis of cyst formation and
      progressive enlargement. METHODS: To determine whether EGFR tyrosine kinase
      inhibition is protective in the PCK rat, male and female animals were treated
      with EKI-785 or EKB-569 or with vehicle alone between 3 and 10 weeks of age.
      Biochemical and histomorphometric analysis, immunohistochemistry, immunoblotting,
      enzyme immunoassay, and quantitative reverse transcription-polymerase chain
      reaction (RT-PCR) were used to ascertain the effects of treatment. RESULTS:
      Contrary to other murine models of ARPKD, overexpression and apical
      mislocalization of EGFR were not detected in the PCK rats. Consistent with these
      expression results, EKI-785 or EKB-569 administration had no effect or worsened
      PKD, and had no effect on the development of fibrocystic liver disease. Increased
      renal cAMP and vasopressin V2 receptor expression were observed in the EKI-785
      treated animals. CONCLUSION: EGFR tyrosine kinase inhibition did not protect PCK
      rats from the development of PKD. This may be due to effects on collecting duct
      cAMP that counteract possible beneficial effects on the extracellular-regulated
      protein kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway,
      particularly in the absence of EGFR overexpression or mislocalization. The
      relevance of these observations to the treatment of human cystic kidney diseases
      deserves further study.

PMID- 15496148
TI  - Combining TGF-beta inhibition and angiotensin II blockade results in enhanced
      antifibrotic effect.
AB  - BACKGROUND: Although angiotensin II (Ang II) blockade is rapidly becoming
      standard antifibrotic therapy in renal diseases, current data suggest that Ang II
      blockade alone cannot stop fibrotic disease. New therapies, such as antibodies to
      transforming growth factor-beta (TGF-beta), or drug combinations will be required
      to further slow or halt disease progression. Here, using the anti-Thy1 model of
      glomerulonephritis, the maximally therapeutic dose of the TGF-beta neutralizing
      mouse monoclonal antibody (1D11) was determined and compared with the maximally
      effective dose of enalapril. Then, the effect of combining both treatments at
      maximal doses was determined. METHODS: After disease induction with the anti-Thy1
      antibody, OX-7, increasing doses of 1D11 were given intraperitoneally (IP) on
      days 1, 3, and 5. Enalapril was administered in drinking water from day 1. The
      fibrotic response was assessed at day 6. RESULTS: 1D11 dose-dependently reduced
      fibrosis, with the 0.5 and 5 mg/kg doses showing maximal therapeutic effects,
      reducing period-acid Schiff (PAS) staining by 56% and 45%, respectively.
      Fibronectin and collagen I staining was reduced by 32% to 36%, respectively.
      Glomerular mRNA and production of fibronectin, plasminogen activator inhibitor-1
      (PAI-1), TGF-beta1, and p-Smad2 protein were also reduced. The maximal
      therapeutic effects of 1D11 and enalapril alone were very similar. However,
      combination therapy led to further reduction in disease. Notably, matrix
      deposition was reduced by 80%. CONCLUSION: While 1D11 or enalapril at maximal
      doses reduce fibrosis equally, simultaneous blockade of Ang II and TGF-beta
      reduces fibrotic disease considerably more, offering hope that such drug
      combinations may confer a therapeutic advantage over angiotensin blockade alone.

PMID- 15496149
TI  - Expression of somatostatin in the adult and developing mouse kidney.
AB  - BACKGROUND: Somatostatin (somatotropin release inhibiting factor) (SRIF) has
      potent antiproliferative and antisecretory actions. In the adult kidney,
      somatostatin alters renal blood flow, ion transport, and water permeability.
      While some evidence suggests that SRIF may be produced by adult kidney tubular
      cells, the specific tubules generating SRIF are unknown. Somatostatin has also
      been detected in a variety of embryonic tissues, although it has not been
      described in the developing kidney. Our objective was to determine the expression
      pattern of SRIF in both the adult and embryonic mouse kidney. METHODS: We
      performed reverse transcriptase-polymerase chain reaction (RT-PCR) and
      immunofluorescence for SRIF in developing and adult mouse kidney tissues. We
      localized SRIF by dual or serial labeling immunofluorescence with specific
      markers. RESULTS: Somatostatin mRNA was present in kidneys throughout
      embryogenesis and into adulthood. Starting at embryonic day (E) 12.5, SRIF was
      strongly expressed at the interface of the metanephric mesenchymal cells and the
      basolateral surfaces of ureteric bud trunks. Starting at E16.5, the staining at
      the interface was confined to the peripheral ureteric bud trunks and the clefts
      of newly dividing ureteric bud ampullae. In older embryos, SRIF also appeared in
      medullary tubules that appeared to be maturing thin descending limbs of Henle. In
      the adult kidney, SRIF proteins localized exclusively to medullary thin
      descending limbs of the Henle loop. CONCLUSION: In embryonic kidneys, SRIF is
      expressed first at the interface of the metanephric mesenchyme and basolateral
      ureteric bud and later in maturing thin descending limbs of Henle. Expression in
      the thin descending limb persists in the adult kidney.

PMID- 15496150
TI  - Caveolin-1 in mesangial cells suppresses MAP kinase activation and cell
      proliferation induced by bFGF and PDGF.
AB  - BACKGROUND: Caveolin is a principal component of caveolae and regulates signaling
      in caveolae. Mesangial cells contain many caveolae, and thus manipulation of
      caveolin-1 expression level might be useful to control mesangial cell
      proliferation, which is an important aggravating factor in many renal diseases.
      METHODS: In the present study, we transfected caveolin-1 cDNA to rat primary
      mesangial cells and MES13 cells, and examined the effects on Raf-extracellular
      signal-regulated protein kinase (ERK) kinase (MEK)-mitogen-activated protein
      (MAP) kinase pathway and cell proliferation stimulated by basic fibroblast growth
      factor (bFGF) and platelet-derived growth factor (PDGF). Activity of the kinases
      was analyzed by immunofluorescence labeling and Western blot analysis. RESULTS:
      The overexpression of caveolin-1 inhibited the activation of Raf-1, MEK-1/2, and
      MAP kinase induced by either bFGF or PDGF. Furthermore, it suppressed the cell
      proliferation caused by the cytokines. The effect was specific to the Raf-MEK-MAP
      kinase pathway, because it did not influence activation of Smad2 induced by
      transforming growth factor-beta (TGF-beta). On the contrary, expression of a
      dominant-negative caveolin mutant, DGV-caveolin, augmented activation of MAP
      kinase. CONCLUSION: The result showed that overexpression of caveolin-1 in
      mesangial cells suppresses MAP kinase activation and cell proliferation induced
      by bFGF and PDGF. Because bFGF and PDGF are two major cytokines involved in the
      mesangioproliferative nephritis, the result implies that introduction of caveolin
      1 expression vector is a potential therapeutic tool for the disease.

PMID- 15496151
TI  - Epidermal growth factor receptor inhibition attenuates early kidney enlargement
      in experimental diabetes.
AB  - BACKGROUND: Renal enlargement is an early feature of both human and experimental
      diabetes. Although the precise mechanisms underlying its development are
      incompletely understood, locally active growth factors have been suggested to
      have a key role. Having previously documented increased expression of the
      proproliferative and antiapoptotic growth factor, epidermal growth factor (EGF),
      in early diabetes-related kidney growth, the present study sought to evaluate its
      pathogenetic role by blocking its action with a specific inhibitor. METHODS:
      Sprague-Dawley rats were randomized to receive streptozotocin (diabetic) or
      buffer (control) and then further randomized to receive either vehicle or the
      inhibitor of the EGF receptor tyrosine kinase, PKI 166 (100 mg/kg/day) for 2 days
      and 3 weeks following streptozotocin administration. RESULTS: Experimental
      diabetes was associated with an increase in kidney weight and tubular epithelial
      cell proliferation as identified by increased expression of proliferating cell
      nuclear antigen (PCNA) and 5-bromo-2'-deoxyuridine (BrdU) incorporation. PKI 166
      resulted in a 30% reduction in kidney weight in diabetic rats (P < 0.01) and
      reduced tubular epithelial cell proliferation (P < 0.01). In addition, EGF
      receptor inhibition also led to a 40% increase in tubular epithelial cell
      apoptosis at 3 weeks (P < 0.01). Diabetes-associated glomerular enlargement was
      similarly attenuated by PKI 166, although glomerular hyperfiltration was
      unaffected. CONCLUSION: These findings suggest that the EGF-EGF receptor (EGFR)
      axis has a significant role in the development of early diabetes-related kidney
      growth. The impact of EGFR inhibition on the later development of renal
      dysfunction, however, remains to be determined.

PMID- 15496152
TI  - The renin-angiotensin system blockade does not prevent renal interstitial
      fibrosis induced by aristolochic acids.
AB  - BACKGROUND: Experimental aristolochic acid nephropathy (AAN), characterized by
      interstitial fibrosis, tubular atrophy, and chronic renal failure, was reported
      after 35-day injections of aristolochic acids (AA) to salt-depleted male Wistar
      rats. The link between renal fibrosis and the renin-angiotensin system (RAS) in
      this model remains unknown. METHODS: We investigated the impact of sodium diets
      (low and normal), of RAS inhibition with enalapril (ENA) alone, or combined with
      candesartan (CSN) for 35 days, and ENA + CSN for 65 days on AAN development. At
      the end of each observation period, blood pressure and renal angiotensin
      converting enzyme activity were measured, as well as renal functional impairment
      (plasma creatinine increase, proteinuria) and histologic lesions (interstitial
      fibrosis, monocytes/macrophages infiltration, myofibroblasts collagens type I and
      IV, proliferating cells). RESULTS: Sodium intake did not modify renal functional
      and morphologic impairment induced by AA. The RAS blockade by ENA or ENA + CSN in
      rats receiving AA did not result in any statistical difference in terms of renal
      failure, proteinuria, and interstitial fibrosis on day 35 or 65. On day 35, the
      monocytes/macrophages infiltration was significantly decreased by two-fold when
      ENA (P < 0.01) or ENA + CSN (P < 0.01) was given from day 0. CONCLUSION: Our data
      demonstrate that RAS modulation by salt depletion and pharmacologic blockade do
      not influence renal failure and interstitial fibrosis in the rat model of AAN. We
      suggest that pathways of interstitial renal fibrosis may be independent of RAS at
      least in some conditions.

PMID- 15496153
TI  - Gene expression profiling of anti-GBM glomerulonephritis model: the role of NF
      kappaB in immune complex kidney disease.
AB  - BACKGROUND: Immune complexes may cause an irreversible onset of chronic renal
      disease. Most patients with chronic renal disease undergo a final common pathway,
      marked by glomerulosclerosis and interstitial fibrosis. We attempted to draw a
      molecular map of anti-glomerular basement membrane (GBM) glomerulonephritis in
      mice using oligonucleotide microarray technology. METHODS: Kidneys were harvested
      at days 1, 3, 7, 11, and 16 after inducing glomerulonephritis by using anti-GBM
      antibody. In parallel with examining the biochemical and histologic changes, gene
      expression profiles were acquired against five pooled control kidneys. Gene
      expression levels were cross-validated by either reverse transcription-polymerase
      chain reaction (RT-PCR), real-time PCR, or immunohistochemistry. RESULTS:
      Pathologic changes in anti-GBM glomerulonephritis were confirmed in both BALB/c
      and C57BL/6 strains. Among the 13,680 spotted 65mer oligonucleotides, 1112 genes
      showing significant temporal patterns by permutation analysis of variance (ANOVA)
      with multiple testing correction [false discovery ratio (FDR) < 0.05] were chosen
      for cluster analysis. From the expression profile, acute inflammatory reactions
      characterized by the elevation of various cytokines, including interleukin (IL)-1
      and IL-6, were identified within 3 days of disease onset. After 7 days, tissue
      remodeling response was prominent with highly induced extracellular-matrix (ECM)
      genes. Although cytokines related to lymphocyte activation were not detected,
      monocyte or mesangial cell proliferation-related genes were increased. Tumor
      necrosis factor-alpha (TNF-alpha) and nuclear factor-kappaB (NF-kappaB) pathway
      were consistently activated along the entire disease progression, inducing
      various target genes like complement 3, IL-1b, IL-6, Traf1, and Saa1. CONCLUSION:
      We made a large-scale gene expression time table for mouse anti-GBM
      glomerulonephritis model, providing a comprehensive overview on the mechanism
      governing the initiation and the progression of inflammatory renal disease.

PMID- 15496154
TI  - C5b-9 regulates peritubular myofibroblast accumulation in experimental focal
      segmental glomerulosclerosis.
AB  - BACKGROUND: In human focal segmental glomerulosclerosis (FSGS), the
      tubulointerstitial deposition of the complement (C5b-9) membrane attack complex
      is correlated with interstitial myofibroblast accumulation and proteinuria. Here,
      we hypothesized that C5b-9 formation regulates renal myofibroblast accumulation
      in Adriamycin nephropathy. METHODS: Adriamycin nephropathy was induced in
      complement C6-sufficient (C6+) and C6-deficient (C6-) piebold viral glaxo (PVG)
      rats. Groups of animals (N= 7 to 8 each) were examined on days 21 and 42. A group
      of C6+ animals, injected with vehicle, served as the control group. RESULTS: C6+
      and C6- rats with Adriamycin nephropathy had equivalent proteinuria. C5b-9
      deposition was increased and present on the apical surface of proximal tubular
      epithelial cells (day 21 and 42) and peritubular region (day 42 only) in C6+ rats
      with Adriamycin nephropathy, and absent in C6- rats. Peritubular myofibroblast
      accumulation increased in a time-dependent manner in C6+ proteinuric rats
      (control 1.2 +/- 0.4; Adriamycin nephropathy day 21 11.0 +/- 0.7; Adriamycin
      nephropathy day 42 19.8 +/- 1.7 cells per high power field). In C6- rats this
      increase was blunted by 87% and 56% on days 21 and 42, respectively (P < 0.01),
      and was associated with reduced interstitial extracellular matrix (ECM)
      deposition. Tubulointerstitial injury, tubular vimentin and interstitial monocyte
      accumulation were also reduced in C6- rats with Adriamycin nephropathy on day 21,
      but not at day 42. In contrast, the increase in periglomerular myofibroblast
      accumulation and glomerulosclerosis in Adriamycin nephropathy were not altered by
      C6 deficiency. CONCLUSION: These data suggest that glomerular ultrafiltration of
      complement components and the intratubular formation of C5b-9 is a specific
      promotor of peritubular myofibroblast accumulation in FSGS.

PMID- 15496155
TI  - Albumin up-regulates the type II transforming growth factor-beta receptor in
      cultured proximal tubular cells.
AB  - BACKGROUND: Clinical and experimental observations suggest that proteinuria is
      not merely a marker of chronic nephropathies, but may also be involved in the
      progression to end-stage renal failure. Filtered proteins are taken up by tubular
      cells, and overwhelming this system may lead to tubular synthesis of various
      proinflammatory and profibrogenic cytokines, including transforming growth factor
      beta (TGF-beta). TGF-beta acts by first binding to specific receptors. We studied
      in an in vitro system using a well-defined mouse proximal tubular cell line (MCT
      cells) whether fatty acid-free bovine albumin modulates expression of specific
      receptors for TGF-beta. METHODS: MCT (and LLC-PK1) cells were challenged in serum
      free medium with different concentrations of albumin. Activation of a local renin
      angiotensin system was tested by real-time polymerase chain reaction (PCR) for
      renin and angiotensinogen transcripts and determination of secreted angiotensin
      II (Ang II) by enzyme-linked immunosorbent assay (ELISA). Some cells were also
      treated with the AT1 receptor antagonist losartan. TGF-beta receptor types I and
      II mRNA levels were determined by Northern analysis whereas protein abundance was
      measured by Western blots. To test for a functional consequence of up-regulated
      TGF-beta receptors, MCT cells were preincubated with albumin and subsequently
      treated with low-dose TGF-beta that normally does not induce collagen type IV
      expression by itself. Downstream signaling events were detected by Western blots
      for phosphorylated Smad2. Scatchard assays with [125I]TGF-beta1 were performed to
      estimate affinity and number of specific binding sites. Different length TGF-beta
      type II promoter constructs linked to CAT reporter were transiently transected
      into MCT cells to determine transcriptional activity. RESULTS: Incubation of MCT
      cells with 0.5 to 10 mg/mL albumin leads to an increase in type II TGF-beta
      receptor mRNA and protein expression without influencing type I receptors. An
      increase in type II TGF-beta receptor protein expression was detected after 12
      hours of albumin incubation and was still detectable after 48 hours. The albumin
      mediated increase in type II TGF-beta receptor mRNA was attenuated in the
      presence of 1 micromol/L losartan, suggesting involvement of a local renin
      angiotensin system. MCT cells treated with albumin significantly increased
      expression of angiotensinogen and renin transcripts and also secreted more Ang II
      into the culture supernatant. Analysis of transcriptional activity showed that
      promoter segments containing activating protein (AP-1)-binding sites are
      necessary for albumin-induced transcription of the TGF-beta type II receptor.
      Binding assays revealed that albumin treatment significantly increased the
      overall binding sites as well as the affinity for TGF-beta. This effect had
      functional consequences because MCT cells pretreated with albumin reacted with a
      stronger TGF-beta-mediated phosphorylation of down-stream Smad2 and also
      increased collagen IV expression compared with control cells. CONCLUSION: Our
      findings indicate that albumin up-regulates ligand-binding TGF-beta receptors on
      cultured proximal tubular cells. Albumin-induced activation of local Ang II
      production appears to be responsible for this effect. This may amplify the matrix
      stimulatory actions of TGF-beta on tubular cells and could be a novel mechanism
      for how proteinuria exhibits pathophysiologic effects on tubular cells ultimately
      leading to tubulointerstitial fibrosis.

PMID- 15496156
TI  - Heterozygous mice for TGF-betaIIR gene are resistant to the progression of
      streptozotocin-induced diabetic nephropathy.
AB  - BACKGROUND: Transforming growth factor-beta (TGF-beta) receptor complex and its
      downstream Smad signaling intermediates constitute an extracellular matrix (ECM)
      accumulation pathway. METHODS: In the present study, we examined whether
      decreased expression of the TGF-beta type II receptor (TGF-betaIIR) in TGF
      betaIIR gene heterozygous (TGF-betaIIR+/-) (HT) mice could inhibit the Smad
      signaling pathway and subsequent progression of renal lesions when streptozotocin
      (STZ) diabetes is induced. RESULTS: At the end of the 28-week experiment after
      STZ injections, wild-type diabetic mice showed severe glomerular hypertrophy and
      mesangial matrix accumulation occasionally featuring nodular glomerulosclerosis.
      In contrast, mean glomerular area and mesangial volume density were significantly
      decreased in the HT diabetic mice as compared with the wild-type diabetic mice.
      Immunostaining for phosphorylated Smad2/Smad3 and TGF-betaIIR in the glomerular
      cells was also significantly reduced in the HT diabetic mice. Southwestern
      histochemistry using digoxigenin-labeled CAGA sequence probes showed that
      localization of labeled probes to the nuclei of glomerular cells in the HT
      diabetic mice was significantly less frequent than that in the wild-type diabetic
      animals. Northern blot analysis showed that alpha1(IV) collagen mRNA levels were
      significantly reduced in the kidney tissue of HT diabetic mice as compared with
      the wild-type diabetic mice. CONCLUSION: These results suggest that decreased
      expression of TGF-betaIIR in the HT diabetic mice can inhibit the progression of
      diabetic renal injury by inhibiting the downstream Smad signaling pathway and
      subsequent ECM gene expression. Thus, TGF-betaIIR appears to play an important
      role in the progression of diabetic nephropathy by mediating intracellular Smad
      signaling.

PMID- 15496157
TI  - Mild hyperhomocysteinemia promotes renal hemodynamic dysfunction without
      histopathologic changes in adult rats.
AB  - BACKGROUND: Hyperhomocysteinemia is able to promote glomerular damage and
      generate tubulointerstitial lesions. These findings were reported in rats with
      unilateral nephrectomy or in weanling rats with normal function, two experimental
      models that are exposed to other concomitant vascular risk factors. The aim of
      this work is to study whether mild hyperhomocisteinemia per se can induce renal
      histopathologic changes in adults rats with normal renal function at either 10 or
      44 weeks of hyperhomocysteinemia. METHODS: Two months old male Wistar rats (N=
      52) were randomly allocated to either a normal control (N= 26) or
      hyperhomocysteinemic (N= 26) group. Control and hyperhomocysteinemic groups had
      free access to either tap water or homocysteine thiolactone 50 mg/kg/day, during
      10 or 44 weeks. Plasma homocysteine levels were determined by a high-performance
      liquid chromatography (HPLC) method. Glomerular filtration rate (GFR) and renal
      plasma flow (RPF) were calculated from inulin and sodium para-aminohippurate
      (PAH) clearance determinations. Structural renal changes were investigated in
      kidneys fixed by perfusion. Histopathologic and morphometric analysis were
      carried out by standard methods. RESULTS: Plasma total homocysteine levels were
      53% (10 weeks) and 56% (44 weeks) higher in hyperhomocysteinemic group compared
      to the control group. GFR and RPF were significantly lower in
      hyperhomocysteinemic than in control group. The histopathologic and morphometric
      studies did not show any differences between the control and hyperhomocysteinemic
      rats at 10 or 44 weeks. CONCLUSION: The present results show that mild
      hyperhomocysteinemia is able to induce renal functional and biochemical
      alterations in male adult rats that are not associated with renal histopathologic
      changes.

PMID- 15496158
TI  - In vitro evidence for immune activating effect of specific AGE structures
      retained in uremia.
AB  - BACKGROUND: Advanced glycation end-products (AGEs) have been identified to be
      accumulated in blood and tissues of patients with end-stage renal disease (ESRD).
      AGEs have been shown to modulate immune competent cell activities and in this way
      they may contribute to the progression of atherosclerosis. All studies in this
      context have been performed, however, with generated mix of glycation compounds,
      and not with structures similar to those encountered in uremia. In the present
      study, the immunologic effect of specific AGE compounds, known to be retained in
      uremia, has been evaluated. METHODS: Four albumin preparations, modified
      chemically at lysine or arginine residues, respectively, to contain N-epsilon
      carboxymethyllysine (CML albumin), N-epsilon-carboxyethyllysine (CEL albumin),
      glyoxal-induced imidazolinones (Arg I albumin) or methylglyoxal-induced
      imidazolinones (Arg II albumin) were applied. Their effect on chemiluminescence
      production, CD14 expression, and the DNA synthesis of calcitriol-differentiated
      HL-60 (monocyte/macrophage phenotype) was studied. RESULTS: The phorbol 12
      myristate 13-acetate (PMA)-stimulated chemiluminescence production of the
      calcitriol differentiated HL-60 cells was enhanced in the presence of CEL albumin
      (44.1 +/- 18.5 vs. 64.7 +/- 28.1 counts 10(3)/30 min) (P < 0.05), Arg I albumin
      (46.4 +/- 18.8 vs. 66.1 +/- 32.6 counts 10(3)/30 min) (P < 0.05) and CML albumin
      (41.9 +/- 25.5 vs. 60.9 +/- 5.5 counts 10(3)/30 min) (P= 0.0625) pointing to an
      increase in free radical production. The latter AGE compounds also significantly
      increased the calcitriol-induced CD14 expression on HL-60 cells (1675 +/- 796 vs.
      2075 +/- 1044; 768 +/- 143 vs. 890 +/- 150; 647 +/- 63 vs. 716 +/- 69 mean
      fluorescence intensity) (P < 0.05, respectively) pointing to an increase in
      expression of the lipopolysaccharide (LPS) receptor. Finally, the DNA synthesis
      of the calcitriol-differentiated HL-60 cells was enhanced in the presence of Arg
      I albumin [34.5 +/- 4.6 vs. 27.7 +/- 9.7% 5-bromo-2'-deoxyuridine (BrdU)-positive
      cells] (P < 0.05) resulting in an increased cell proliferation. CONCLUSION:
      Genuine AGE compounds, as they are encountered in the uremic condition, activate
      leukocyte response, and hence could play a role in uremia related atherogenesis.

PMID- 15496159
TI  - Induction of antioxidant enzymes in murine podocytes precedes injury by puromycin
      aminonucleoside.
AB  - BACKGROUND: An imbalance between the generation of reactive oxygen species (ROS)
      and antioxidant defense mechanisms has been suggested to play an important role
      in podocyte injury in nephrotic syndrome. Experimental nephrotic syndrome induced
      by injection of puromycin aminonucleoside (PAN) into rats is a well-established
      model of nephrotic syndrome, and can be largely prevented by pretreatment with
      antioxidant enzymes (AOE), suggesting that podocyte injury may be mediated by
      ROS. METHODS: To test the hypothesis that PAN-induced podocyte injury is
      modulated in part by podocyte antioxidant defenses, we analyzed AOE activities,
      lipid peroxidation products, and relative ROS levels in podocytes using our
      recently reported in vitro model of PAN-induced podocyte injury. RESULTS: PAN
      treatment induced early increases in both podocyte hydrogen peroxide and
      superoxide and later increases in lipid peroxidation products. Compared to
      baseline activities, PAN also induced significant changes in the major cellular
      AOE activities (maximum increases of 151% for catalase, 134% for superoxide
      dismutase, and 220% for glutathione peroxidase vs. time-matched controls). These
      changes largely preceded the development of extensive podocyte process retraction
      and actin filament disruption, which was maximal at 7 days. CONCLUSION: These
      results demonstrate that (1) PAN treatment induces significant early changes in
      podocyte ROS, (2) podocytes can mount an antioxidant defense against oxidant
      stress, and (3) this protective response is initiated prior to the development of
      extensive oxidant-induced podocyte structural injury. These findings suggest that
      enhancement of podocyte AOE activities represent a potential therapeutic target
      to protect from or ameliorate podocyte injury during nephrotic syndrome.

PMID- 15496160
TI  - Mitochondrial dysfunction is a primary event in renal cell oxalate toxicity.
AB  - BACKGROUND: In cultured renal epithelial cells, exposure to oxalate, a
      constituent of many kidney stones, elicits a cascade of responses that often
      leads to cell death. Oxalate toxicity is mediated via generation of reactive
      oxygen species (ROS) in a process that depends at least in part upon lipid
      signaling molecules that are generated through membrane events that culminate in
      phospholipase A2 (PLA2) activation. The present studies asked whether
      mitochondria, a major site of ROS production, were targets of oxalate toxicity,
      and if so, whether mitochondrial responses to oxalate were mediated by PLA2
      activation. METHODS: Effects of oxalate and various lipids on mitochondrial
      membrane potential (DeltaPsim) were measured in Madin-Darby canine kidney (MDCK)
      cell monolayers using 5,5',6,6'-tetrachloro 1,1',3,3'
      tetraethylbenzimidazolylcarbocyanine iodide (JC-1), a DeltaPsim-sensitive dye.
      Other studies assayed caspases, serine proteases activated during apoptosis, in
      response to oxalate or lipid signaling molecules. Additional studies asked
      whether oxalate or lipids produced by PLA2 activation promoted ROS formation in
      isolated renal mitochondria. RESULTS: Oxalate exposure decreased MDCK cell
      DeltaPsim within 30 minutes, a response attenuated by arachidonyl trifluoromethyl
      ketone (AACOCF3), an inhibitor of cytosolic PLA2 (cPLA2). Exposure to arachidonic
      acid or to lysophosphatidylcholine (lyso-PC), lipid products of PLA2 activation,
      or to ceramide, another lipid signal generated in MDCK cells following oxalate
      exposure, also depolarized MDCK cell DeltaPsim and increased the number of
      caspase-positive cells. Isolated renal mitochondria responded to oxalate,
      arachidonic acid, lyso-PC, and ceramide by increasing their accumulation of ROS,
      lipid peroxides, and oxidized thiol proteins. CONCLUSION: These studies suggest
      that lipid signaling molecules released after oxalate-induced PLA2 activation
      trigger marked, rapid changes in mitochondrial function that may mediate toxicity
      in renal epithelial cells.

PMID- 15496161
TI  - Podocyte foot process effacement is not correlated with the level of proteinuria
      in human glomerulopathies.
AB  - BACKGROUND: Nephrotic syndromes result from increased glomerular permeability to
      proteins and are structurally believed to be associated with podocyte foot
      process effacement. Despite increasing knowledge of the molecular composition of
      the glomerular filtration barrier, the relationship between proteinuria and foot
      process effacement is unclear. METHODS: We conducted a morphologic study on the
      relationship between podocyte foot process effacement and proteinuria. Electron
      microscope pictures of glomerular capillaries were randomly taken from 27 cases
      in various stages of minimal change nephrotic syndrome (MCNS), from six cases of
      IgA nephropathy (IgAN) with high proteinuria and from seven control kidneys. From
      each picture, the mean width of the foot processes (FPW) was quantitated.
      RESULTS: In normal kidney the mean FPW was 580 +/- 40 nm. In biopsies from
      patients with MCNS without treatment, foot processes were diffusely effaced,
      reflected by a FPW of 1600 +/- 440 nm. In biopsies from patients with MCNS
      relapsing under prednisolone treatment, foot processes were significantly less
      effaced than in untreated MCNS (FPW 920 +/- 200 nm). In biopsies displaying IgAN,
      effacement was significantly more segmental than in untreated MCNS (FPW 800 +/-
      170 nm). Proteinuria did not differ significantly among the groups. Neither in
      MCNS nor in IgAN was the extent of foot process effacement correlated with the
      level of proteinuria. CONCLUSION: Podocyte foot process effacement is not
      correlated with proteinuria. The differences in podocyte effacement between MCNS,
      MCNS relapsing under prednisolone treatment, and IgAN may point to different
      mechanisms of podocyte injury in these diseases.

PMID- 15496162
TI  - CCR and CC chemokine expression in relation to Flt3 ligand-induced renal
      dendritic cell mobilization.
AB  - BACKGROUND: We investigated the expression and function of CC chemokine receptors
      (CCR) on highly-purified kidney and blood dendritic cells isolated from mice in
      which dendritic cells were mobilized with fms-like tyrosine 3 kinase ligand
      (Flt3L). METHODS: CCR and CC chemokine expression were determined by RNase
      protection assay or flow cytometry, and dendritic cell migratory responses
      assayed using Transwell chambers. Chemokine production in renal tissue was
      detected by immunofluorescence staining. Trafficking of fluorochrome-labeled
      dendritic cells was monitored in vivo. RESULTS: Freshly-isolated renal dendritic
      cells expressed mRNA for CCR1, 2, 5, and 7 and CCR1 and 5 protein. They did not
      migrate to inducible chemokines--CCL3 [macrophage inflammatory protein (MIP)
      1alpha], CCL5 [regulated upon activation, normal T cell expressed and secreted
      (RANTES)], or CCL20 (MIP-3alpha). Following lipopolysaccharide (LPS) stimulation,
      the dendritic cells down-regulated CCR1, 2, and 5 expression, up-regulated or
      sustained signals for CCR7, and migrated to the constitutively expressed ligands
      CCL19 (MIP-3beta) and CCL21 (secondary lymphoid tissue chemokine). Normal kidneys
      expressed weak message for CCL2, 3, and 4, with stronger signals for CCL5 and 19.
      Intrarenal CCL5 production was enhanced by Flt3L administration, in association
      with marked increases in interstitial CD45+ mononuclear cells. Mobilized blood
      dendritic cells migrated to CCR2 and CCR5 ligands and trafficked to renal
      intertubular sites following adoptive (intravenous) transfer. Their migration to
      the CCR5 ligand MIP-1beta (CCL4) and homing to kidneys of Flt3L-treated
      recipients were inhibited by CCR5 antagonism. CONCLUSION: These data implicate
      specific CCR and their ligands in regulation of the dendritic cell constituency
      of the kidney. CCR5 antagonism inhibits their directed migration and intrarenal
      accumulation.

PMID- 15496163
TI  - Regulation of CLC-Ka/barttin by the ubiquitin ligase Nedd4-2 and the serum- and
      glucocorticoid-dependent kinases.
AB  - BACKGROUND: ClC-Ka and ClC-Kb, chloride channels participating in renal tubular
      Cl- transport, require the coexpression of barttin to become functional.
      Mutations of the barttin gene lead to the Bartter's syndrome variant BSND,
      characterized by congenital deafness and severe renal salt wasting. Barttin bears
      a proline-tyrosine motif, a target structure for the ubiquitin ligase Nedd4-2,
      which mediates the clearance of channel proteins from the cell membrane. Nedd4-2
      is, in turn, a target of the serum- and glucocorticoid-inducible kinase SGK1,
      which phosphorylates and, thus, inactivates the ubiquitin ligase. ClC-Ka also
      possesses a SGK1 consensus site in its sequence. We hypothesized that ClC
      Ka/barttin is stimulated by SGK1, and down-regulated by Nedd4-2, an effect that
      may be reversed by SGK1 and its isoforms, SGK2 or SGK3. METHODS: To test this
      hypothesis, ClC-Ka/barttin was heterologously expressed in Xenopus oocytes with
      or without the additional expression of Nedd4-2, SGK1, SGK2, SGK3, constitutively
      active S422DSGK1, or inactive K127NSGK1. RESULTS: Expression of ClC-Ka/barttin
      induced a slightly inwardly rectifying current that was significantly decreased
      upon coexpression of Nedd4-2, but not the catalytically inactive mutant
      C938SNedd4-2. The coexpression of S422DSGK1, SGK1, or SGK3, but not SGK2 or
      K127NSGK1 significantly stimulated the current. Moreover, S422DSGK1, SGK1, and
      SGK3 also phosphorylated Nedd4-2 and thereby inhibited Nedd4-2 binding to its
      target. The down-regulation of ClC-Ka/barttin by Nedd4-2 was abolished by
      elimination of the PY motif in barttin. CONCLUSION: ClC-Ka/barttin channels are
      regulated by SGK1 and SGK3, which may thus participate in the regulation of
      transport in kidney and inner ear.

PMID- 15496164
TI  - The relationship between cell proliferation, Cl- secretion, and renal cyst
      growth: a study using CFTR inhibitors.
AB  - BACKGROUND: In autosomal-dominant polycystic kidney disease (ADPKD), cAMP
      stimulated cell proliferation and Cl- secretion via the cystic fibrosis
      transmembrane conductance regulator (CFTR) Cl- channel drive the enlargement of
      fluid-filled epithelial cysts. To investigate how CFTR blockers inhibit cyst
      growth, we studied cAMP-dependent Cl- secretion, cell proliferation, and cyst
      growth using type I Madin Darby canine kidney (MDCK) cells as a model of renal
      cyst development and growth. METHODS: We grew MDCK cysts in collagen gels in the
      presence of the cAMP agonist forskolin, measured Cl- secretion with the Ussing
      chamber technique, and assayed cell proliferation using nonpolarized and
      polarized MDCK cells. To inhibit CFTR, we used glibenclamide, 5-nitro-2-(3
      phenylpropylamino)-benzoic acid (NPPB), genistein, and the specific CFTR
      inhibitor CFTRinh-172. As controls, we tested the effects of blockers of other
      types of apical membrane Cl- channels and inhibitors of basolateral membrane ion
      channels and transporters. RESULTS: In the absence of inhibitors of
      transepithelial ion transport, forskolin stimulated dramatic cyst growth. CFTR
      blockers and inhibitors of basolateral membrane ion channels and transporters
      retarded cyst growth. In contrast, blockers of other types of apical membrane Cl-
      channels, which were without effect on CFTR, failed to inhibit cyst growth.
      Inhibition of cyst growth by CFTR blockers was correlated with inhibition of cAMP
      stimulated Cl- current (correlation coefficient = 0.81; P < 0.05), but not cell
      proliferation (correlation coefficient = 0.50; P > 0.05). CONCLUSION: Our data
      suggest that CFTR blockers might retard cyst growth predominantly by inhibiting
      fluid accumulation within the cyst lumen.

PMID- 15496165
TI  - Real-time observation of glomerular hemodynamic changes in diabetic rats: effects
      of insulin and ARB.
AB  - BACKGROUND: The progression of diabetic nephropathy is closely related to
      disturbances in glomerular hemodynamics, such as glomerular hypertension and/or
      hyperperfusion. The aim of this study was to observe and to analyze glomerular
      hemodynamics in rats with diabetes mellitus (DM) in vivo using confocal laser
      scan microscopy (CLSM). We also examined the effects of candesartan cilexetil
      (TCV-116), a selective angiotensin II type 1 receptor blocker (ARB), on
      glomerular hemodynamics in DM. METHODS: Munich-Wistar rats were divided into six
      groups: (1) four-day control; (2) four-day DM; (3) 28-day control; (4) 28-day DM;
      (5) DM treated with insulin; (6) DM treated with TCV-116. The kidney-to-body
      weight ratio, glomerular volume, and proteinuria were estimated. Glomerular
      hemodynamic changes were observed using CLSM and renal expression of endothelial
      nitric oxide synthase (eNOS), and neuronal nitric oxide synthase (nNOS) was
      evaluated by immunofluorescence. RESULTS: The kidney-to-body weight ratio,
      glomerular volume, the diameters of afferent arterioles (AA) and efferent
      arterioles (EA), erythrocyte velocities within glomeruli, and volume flow in
      glomerular capillary loops in four-day DM were significantly higher than in
      control rats, and increases were even more pronounced in the 28-day DM. TCV-116
      treatment ameliorated all these findings and significantly decreased proteinuria,
      but there was no effect on the blood glucose level. On the other hand, insulin
      treatment was followed by normalization of all these changes induced in DM.
      Enhanced renal expression of eNOS in DM was suppressed when treated with either
      TCV-116 or insulin, while expression of nNOS was unaltered among the four groups.
      CONCLUSION: This imaging procedure allowed us to evaluate glomerular
      microcirculation in vivo, including the diameters of AA and EA, erythrocyte
      velocity, and volume flow. DM significantly induced glomerular hemodynamic
      alteration and renal hypertrophy. DM treated with either insulin or ARB
      ameliorated these changes. This study shows that progress in imaging technology
      promises to make major contributions to revealing the involvement of hemodynamic
      changes in glomerular diseases, aiding prognosis and the monitoring of
      therapeutic effects, as well.

PMID- 15496166
TI  - AT1 receptors mediate angiotensin II-induced release of nitric oxide in afferent
      arterioles.
AB  - BACKGROUND: Recent studies have indicated that angiotensin II (Ang II) possibly
      activates the nitric oxide (NO) system. We investigated the role of AT receptor
      subtypes (AT-R) in mediating the Ang II-induced NO release in afferent arterioles
      (Af) of mice. METHODS: Isolated Af of mice were perfused, and the isotonic
      contraction measured. Further, NO release was determined using DAF-FM, a
      fluorescence indicator for NO. Moreover, we qualitatively assessed the expression
      of AT-R at the mRNA level using reverse transcription-polymerase chain reaction
      (RT-PCR). RESULTS: Ang II reduced luminal diameters dose dependently (67.3 +/-
      6.3% at 10(-6) mol/L). Inhibition of AT2-R with PD123.319 did not change the Ang
      II contractile response. AT1-R blockade with ZD7155 inhibited contraction.
      Stimulation of AT2-R during AT1-R inhibition with ZD7155, and preconstriction
      with norepinephrine (NE) had no influence on the diameter. Drug application via
      the perfusion pipette changed flow and pressure, and enhanced NO fluorescence by
      DeltaF = 4.0 +/- 0.4% (N= 14, background). Luminal application of Ang II (10(-7)
      mol/L) increased the NO fluorescence by DeltaF = 9.9 +/- 1.2% (N= 8). AT1-R
      blockade blunted the increase to background levels (DeltaF to 4.0 +/- 0.3%, N= 6,
      P < 0.05), but AT2-R blockade did not (8.1 +/- 0.9%, N= 9). L-NAME nearly
      abolished the Ang II effect on the NO fluorescence (DeltaF = 1.6 +/- 0.5% (N= 8).
      NE did not increase NO release beyond the background levels. RT-PCR showed
      expression of both AT1-R and AT2-R. CONCLUSION: The results indicate an Ang II
      induced NO release in Af of mice, which is mediated by AT1-R. Thus, Ang II
      balances its own constrictor action in Af. This control mechanism is very
      important in view of high renin and angiotensin II concentration in the
      juxtaglomerular apparatus.

PMID- 15496167
TI  - Vasopeptidase inhibitor restores the balance of vasoactive hormones in
      progressive nephropathy.
AB  - BACKGROUND: The mechanism(s) underlying greater renoprotection of combined
      blockade of angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP)
      by vasopeptidase over ACE inhibitors are ill defined. We previously found that
      progressive renal disease is associated with increased renal synthesis of
      endothelin-1 (ET-1) in the face of reduced generation of renal nitric oxide (NO)
      in the remnant kidney model. Here we compared changes in urinary excretion of ET
      1 and nitrite/nitrate, markers of renal ET-1, and NO synthesis, respectively, and
      urinary cGMP, an indirect index of renal atrial natriuretic peptide (ANP)
      synthesis, after administration of vasopeptidase or ACE inhibitor in rats with
      renal mass reduction (RMR). METHODS: Twenty-one days after 5/6 nephrectomy, after
      the onset of hypertension and overt proteinuria, rats were divided in 3 groups
      (N= 7-8) and given daily by gavage: vehicle, the vasopeptidase inhibitor AVE7688
      (3 mg/kg bid), or enalapril (5 mg/kg bid) until day 90. Normal rats (N= 5) served
      as control rats. RESULTS: Systolic blood pressure in RMR rats was equally
      controlled by AVE7688 and enalapril. AVE7688 resulted in a significant
      antiproteinuric effect, with urinary protein levels being reduced on average by
      83% in respect to vehicle (88 +/- 28 vs. 518 +/- 27 mg/day, P < 0.0001).
      Enalapril achieved a 47% reduction in proteinuria (277 +/- 81 mg/day, P < 0.01
      vs. vehicle) to levels that remained higher (P < 0.01), however, than those after
      AVE7688. Renal function impairment and glomerular and tubular changes were
      significantly (P < 0.05 vs. vehicle) ameliorated by AVE7688, and partially
      affected by enalapril. AVE7688 reduced the abnormal urinary excretion of ET-1 of
      RMR animals (98 +/- 8 vs. vehicle: 302 +/- 50 pg/24 h, P < 0.001) more than
      enalapril (159 +/- 14 pg/24 h, P < 0.05 vs. AVE7688). Consistently, AVE7688 was
      more effective than enalapril in augmenting renal synthesis of NO (2487 +/- 267
      and 1519 +/- 217 vs. vehicle: 678 +/- 71 nmol/15 h; P < 0.001, AVE7688 vs.
      vehicle, P < 0.01 AVE7688 vs. enalapril). AVE7688 significantly increased urinary
      cGMP (78 +/- 6 vs. vehicle 45 +/- 9 nmol/24 h; P < 0.01). CONCLUSION: The
      superior renoprotection achieved by AVE7688 over enalapril in progressive renal
      injury is due to the correction of the altered balance of
      vasoconstrictor/vasodilator mediators in the kidney.

PMID- 15496168
TI  - Ovariectomy enhances renal cortical expression and function of cyclooxygenase-2.
AB  - BACKGROUND: Cyclooxygenase-2 (COX-2) inhibitors are used as analgesics in
      postmenopausal women, who develop edema and require a salt-restricted diet. This
      study was performed to determine the renal expression of COX-2 and on COX-2
      dependent regulation of renal blood flow (RBF) in ovariectomized rats. METHODS:
      Sprague-Dawley rats were divided into 4 groups: sham-operated rats fed a normal
      salt diet (Sh+NS) or a low-salt diet (Sh+LS), and bilaterally ovariectomized rats
      fed a normal-salt diet (Ox+NS) or a low-salt diet (Ox+LS) (N= 6 in each group).
      Estrogen replacement therapy was performed on other ovariectomized rats. A renal
      clearance study was performed in anesthetized animals. RESULTS: Ovariectomy
      increased renal cortical COX-2 expression independently of dietary salt intake
      (Sh+NS <Ox+N; Sh+LS <Ox+LS). Inhibition of COX-2 by NS398 reduced the urinary
      excretion of 6-keto-prostaglandin F1alpha in all 4 groups, although the reduction
      was greater in the Ox+LS group than in the Ox+NS and Sh+LS groups, which in turn
      had a greater reduction than the Sh+NS group. RBF significantly decreased in
      every group except the Sh+NS group, but no effect on blood pressure, inulin
      clearance, or urinary sodium excretion was seen. The decrease in RBF was
      significantly greater in the Ox+LS group than in the Sh+LS and Ox+NS group. The
      decrease in RBF was dependent on cortical RBF in the Sh+LS and Ox+NS groups, and
      on both cortical and medullary RBF in the Ox+LS group. Estrogen replacement
      therapy reversed the ovariectomy-induced changes. CONCLUSION: Estrogen-dependent
      COX-2 expression plays an important role in the RBF regulation in female rats.

PMID- 15496169
TI  - Homocysteine activates NADH/NADPH oxidase through ceramide-stimulated Rac GTPase
      activity in rat mesangial cells.
AB  - BACKGROUND: We recently demonstrated that homocysteine (Hcys) increases
      superoxide (O2-) production via NADH/NADPH oxidase in renal mesangial cells. This
      O2- production contributes to increased expression of tissue inhibitor of
      metalloproteinase (TIMP-1) and consequent deposition of collagen in response to
      Hcys. However, the mechanism by which Hcys activates NADH/NADPH oxidase remains
      unknown. Given that ceramide is an intracellular activator of this oxidase in
      several cell types, the present study tests the hypothesis that Hcys activates
      NADH/NADPH oxidase through a ceramide-mediated signaling pathway in rat mesangial
      (MG) cells, resulting in O2- production. METHODS: Rat MG cells were incubated
      with L-homocysteine (L-Hcys) to determine the mechanism by which Hcys activates
      NADH/NADPH oxidase. Thin layer chromatography (TLC), Western blot analysis, Rac
      GTPase activity pull down assay, and NADH/NADPH oxidase activity measurements
      were performed. RESULTS: TLC analysis demonstrated that L-Hcys increased de novo
      production of ceramide in MG cells. L-Hcys and increased ceramide did not alter
      the amount of NADH/NADPH oxidase subunit p47phox and p67phox in both membrane and
      cytosolic fractions from MG cells. However, L-Hcys or ceramide markedly increased
      the level of GTP-bound Rac, which was accompanied by enhanced activity of
      NADH/NADPH oxidase. These Hcys or ceramide-induced actions were substantially
      blocked by a Rac GTPase inhibitor, GDPbetaS, and a de novo ceramide synthesis
      inhibitor, fumonisin B1 (FB1). CONCLUSION: These results indicate that Hcys
      activates NADH/NADPH oxidase by stimulating de novo ceramide synthesis, and
      subsequently enhancing Rac GTPase activity in rat MG cells. This ceramide-Rac
      GTPase signaling pathway may mediate Hcys-induced oxidative stress in these
      glomerular cells.

PMID- 15496170
TI  - Oxidative stress is enhanced in correlation with renal dysfunction: examination
      with the redox state of albumin.
AB  - BACKGROUND: Cardiovascular disease is known to be the most important complication
      among patients with renal failure, and oxidative stress has been proposed to play
      a major role as the source of such complications. Human serum albumin (HSA) is
      composed of human mercaptoalbumin (HMA) with cysteine residues having reducing
      powers, of reversibly oxidized human non-mercaptoalbumin-1 (HNA-1), and strongly
      oxidized human non-mercaptoalbumin-2 (HNA-2). METHODS: We used the "redox state
      of HSA" as a marker to investigate the current status of oxidative stress in
      predialysis patients with renal failure. The subjects were 55 nondialysis
      patients (31 males and 24 females) with chronic renal diseases, and having
      various degrees of renal function. The subjects' redox state of HSA was
      determined by a high-performance liquid chromatographic (HPLC) procedure, and the
      results presented in terms of the ratios between HNA-total(HNA-1 + HNA-2) and HNA
      2. RESULTS: The values for each fraction of HNA-total (f(HNA-total)) and f(HNA-2)
      were increased with a decrease of renal functions, and a significant positive
      correlation with serum creatinine (R= 0.529, P < 0.0001 and R= 0.618, P < 0.0001)
      was detected. Multiple (forward stepwise) regression analysis using f(HNA-total)
      and f(HNA-2) as the criterion variables was performed, and creatinine was adopted
      as significant explanatory variable in both equations. CONCLUSION: We found that
      even before dialysis, oxidative stress was enhanced in correlation with the level
      of renal dysfunction among patients with chronic renal failure. In the future,
      antioxidant strategies should become part of treatment for predialysis renal
      failure.

PMID- 15496171
TI  - Quantitative amino acid and proteomic analysis: very low excretion of
      polypeptides >750 Da in normal urine.
AB  - BACKGROUND: Quantitative data on protein and polypeptide excretion in normal
      urine are lacking. In Fanconi syndrome, failure of proximal tubular protein
      reabsorption leads to 'tubular' proteinuria, but little is known about peptide
      excretion. METHODS: Urine from normal (N=5) and Fanconi patients (Dent's disease,
      N=2; Lowe syndrome, N=3) was fractionated by size-exclusion chromatography into
      proteins (>10 kD) and smaller polypeptides. Each fraction was subjected to amino
      acid analysis after acid hydrolysis. In complementary proteomic approaches,
      urinary polypeptides were each subjected to reversed-phase high-performance
      liquid chromatography (HPLC) followed by matrix-assisted laser
      desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) and nano
      flow liquid chromatography directly coupled to electrospray ionization/tandem
      mass spectrometry (NanoLC-ESI-MS/MS) before and after tryptic digestion. RESULTS:
      Based on amino acid composition, normal human urine, excluding Tamm-Horsfall
      protein, contains 33.7 +/- 10.7 mg protein per 24 hr (mean +/- SEM) protein
      defined as polypeptide >10 kD; peptide content in range 750 Da to 10 kD is 22.0
      +/- 9.6 mg. Fanconi patients excrete greatly increased amounts of protein, 1740
      +/- 660 mg/24 hr, and peptide, 446 +/- 145 mg/24 hr. Peptides 2 to 5 kD were
      present in 12.9- +/- 3.9-fold excess in Fanconi compared with normal urine. In
      contrast, free amino acid excretion in Fanconi was elevated only 2.14- +/- 0.73
      fold. Mass spectrometric techniques determined that the major form of albumin in
      both normal and Fanconi urine was the full-length protein, and did not detect
      significant peptides of nonrenal origin. CONCLUSION: There is only very low
      excretion of polypeptides >750 Da in normal human urine. In Fanconi syndrome,
      excretion of unknown peptides of mass 2 to 5 kD, possibly relevant to the
      development of renal failure, is greatly increased.

PMID- 15496172
TI  - Kidney and anemia in familial amyloidosis type I.
AB  - BACKGROUND: Familial amyloid polyneuropathy (FAP) type I is caused by a mutated
      transthyretin (TTR V30M) and characterized by a sensorimotor and autonomic
      neuropathy. Renal, cardiac, and ocular abnormalities can also occur. Anemia has
      been described in previous reports, but its prevalence in Portuguese FAP patients
      is not precisely known. The aim of this study was to estimate the prevalence of
      anemia in FAP type I Portuguese patients and to evaluate the contribution of
      erythropoietin (Epo) to its genesis. METHODS: A retrospective cross-sectional
      study was undertaken to determinate the prevalence and characteristics of anemia
      in 165 FAP patients. For comparison analysis, 3 control groups were also
      evaluated, 1 group of 46 apparently healthy subjects, 1 group of 17 asymptomatic
      carriers of FAP-trait, and a group of 14 non-FAP patients with chronic renal
      insufficiency. Serum Epo levels were analyzed in all groups. RESULTS: Anemia was
      present in 24.8% of symptomatic FAP patients. Iron stores, B12 vitamin, and serum
      folate levels were normal. FAP patients presented significantly lower serum Epo
      levels than healthy controls (P= 0.003). Epo levels were found lower than
      expected for the degree of anemia and in 17.5% were undetectable. Low Epo values
      were observed independently of the presence of renal failure or anemia, and
      sometimes preceded clinical disease. CONCLUSION: Anemia in FAP type I is a common
      manifestation. The results clearly suggest a defective endogenous Epo production
      in the genesis of the anemia.

PMID- 15496173
TI  - Survival following parathyroidectomy among United States dialysis patients.
AB  - BACKGROUND: Secondary hyperparathyroidism (SHPTH) is highly prevalent among
      persons with end-stage renal disease (ESRD). SHPTH has been linked to uremic bone
      disease, vascular calcification, and a higher risk of death. Parathyroidectomy
      (PTX) can dramatically reduce parathyroid hormone (PTH) and phosphate levels;
      however, the relationship between PTX and survival is not known. METHODS: We
      conducted an observational matched cohort study utilizing data from the United
      States Renal Database System (USRDS) in which 4558 patients undergoing a first
      PTX while on hemodialysis or peritoneal dialysis were individually matched by
      age, race, gender, cause of ESRD, dialysis duration, prior transplantation
      status, and dialysis modality to 4558 control patients who did not undergo PTX.
      Patients were followed from the date of PTX until they died or were lost to
      follow-up. RESULTS: The 30-day postoperative mortality rate following PTX was
      3.1%. Long-term relative risks of death among patients undergoing PTX were
      estimated to be 10% to 15% lower than those of matched control patients not
      undergoing surgery. Survival curves between the 2 groups crossed 587 days
      following PTX. Median survival was 53.4 months (95% CI: 51.2-56.4) in the PTX
      group, and 46.8 months (95% CI: 44.7-48.9) in the control group. CONCLUSION: PTX
      was associated with higher short-term, and lower long-term, mortality rates among
      U.S. patients receiving chronic dialysis. Measures to attenuate SHPTH may play an
      important role in reducing mortality among patients with end-stage renal disease.

PMID- 15496174
TI  - Kidney function is inversely associated with coronary artery calcification in men
      and women free of cardiovascular disease: the Framingham Heart Study.
AB  - BACKGROUND: Among patients with end-stage renal disease (ESRD), the risk of
      cardiovascular disease is 10 to 20 times higher than the general population.
      Adults with ESRD have increased coronary-artery calcification (CAC) detected by
      electron-beam computed tomography (EBCT). Because the risk of coronary heart
      disease is increased even at moderate declines in kidney function, we sought to
      test whether high CAC scores are seen among those with mild reductions in kidney
      function. METHODS: Men and women free of symptomatic cardiovascular disease
      underwent EBCT. Coronary calcium was quantified using the method described by
      Agatston. Renal function was estimated by glomerular filtration rate (GFR).
      Spearman correlation coefficients were used to test the association between GFR
      and CAC. RESULTS: Three hundred nineteen subjects (162 men/157 women), mean age
      60, were included. Mean GFR was 86 +/- 23 mL/min/1.73 m2 (range 31-169; 10% with
      GFR <60 mL/min/1.73 m2). The median CAC scores by quartile of GFR were 85.9,
      48.1, 7.9, and 2.7. Overall, the unadjusted correlation of GFR and CAC was -0.28
      (P < 0.0001). This remained significant after adjustment for age and sex (-0.11,
      P < 0.05), and additionally after adjustment for body mass index (-0.11, P <
      0.05), hypertension (-0.11, P < 0.05), or total cholesterol (-0.12, P= 0.04). A
      similar correlation was noted after multivariable adjustment (-0.10, P < 0.08).
      CONCLUSION: Mild declines in kidney function are associated with subclinical
      coronary artery calcification in a sample of subjects free of clinically apparent
      cardiovascular disease. This might help explain the increased risk of
      cardiovascular disease among individuals with renal dysfunction. Larger ongoing
      studies are needed to better quantify this finding.

PMID- 15496175
TI  - Determinants of coronary artery calcification in diabetics with and without
      nephropathy.
AB  - BACKGROUND: In the general population, including those with diabetes mellitus,
      coronary artery calcification (CAC) correlates with atherosclerotic plaque
      burden. On the other hand, accumulating evidence suggests that disordered mineral
      metabolism significantly contributes to the vascular calcification in individuals
      with end-stage renal disease (ESRD). METHODS: In order to determine the relative
      contribution of accelerated atherosclerosis and disordered mineral metabolism to
      CAC in chronic kidney disease, a pilot study of 90 patients with type 2 diabetes
      mellitus was done [age, 40-65 years; normoalbuminuria, N= 30; diabetic
      nephropathy (DN), N= 60]. RESULTS: CAC was more prevalent and severe among
      individuals with DN compared to diabetic controls (odds ratio for prevalence 8.1,
      95% CI 2.3-28.5; median scores, 66 vs. 4, P < 0.001). None of the 4 measures of
      disordered mineral metabolism evaluated in this study (serum calcium, phosphorus,
      parathyroid hormone, and 1,25 di-hydroxy vitamin D levels) correlated with the
      prevalence or severity of CAC, or accounted for the differences seen between DN
      and diabetic controls. On the other hand, the difference in the severity of
      hypertension (number of antihypertensive medications) appeared to account for the
      differences in CAC burden seen between DN and diabetic controls. CONCLUSION: This
      first such study of nondialyzed individuals with DN suggests that, unlike ESRD
      patients, the high CAC burden seen at earlier stages of diabetic chronic kidney
      disease is probably unrelated to disordered mineral metabolism. The relationship
      between the severity of hypertension and CAC burden provides a probable target
      for intervention in the predialysis phase of DN.

PMID- 15496176
TI  - Rapid Communication: relative effect of urinary calcium and oxalate on saturation
      of calcium oxalate.
AB  - BACKGROUND: The study compared the effect of urinary calcium with that of oxalate
      on urinary saturation [relative saturation ratio (RSR)] of calcium oxalate.
      METHODS: A retrospective data analysis was conducted on urinary stone risk
      analysis from 667 patients with predominantly calcium oxalate stones. Urinary RSR
      of calcium oxalate was individually calculated using Equil 2. A "theoretical"
      curve of the relationship between urinary RSR of calcium oxalate and
      concentration of calcium or oxalate was obtained at two stability constants for
      calcium oxalate complex, while varying calcium or oxalate and using group mean
      values for urinary constituents. RESULTS: At the stability constant of 7.07 x
      10(3), the increase in RSR of calcium oxalate was less marked with calcium than
      with oxalate. However, at the stability constant of 2.746 x 10(3) from the Equil
      2 that is considered the "gold standard," calcium and oxalate were equally
      effective in increasing RSR of calcium oxalate. The above theoretical curves
      (relating RSR with calcium or oxalate) were closely approximated by the actual
      curves constructed with data from individual urine samples. Urinary saturation of
      calcium oxalate was equally dependent on urinary concentrations of calcium and
      oxalate (r= 0.75 unadjusted and 0.57 adjusted for variables, and P < 0.0001 for
      calcium; r= 0.73 unadjusted and 0.60 adjusted, P <0.0001 for oxalate).
      CONCLUSION: Among calcium oxalate stone-formers, urinary calcium is equally
      effective as urinary oxalate in increasing RSR of calcium oxalate.

PMID- 15496177
TI  - Differentiation between chronic rejection and chronic cyclosporine toxicity by
      analysis of renal cortical mRNA.
AB  - BACKGROUND: In kidney transplantation, chronic allograft nephropathy (CAN) is the
      major cause of graft loss. Causes of CAN include chronic rejection and chronic
      cyclosporine A (CsA) nephrotoxicity. It is necessary to differentiate between
      these two entities in order to apply the appropriate therapeutic regimen for the
      individual patient, but this is hampered by the lack of discriminating functional
      and morphologic parameters. We investigated whether renal cortical mRNA levels
      for several matrix proteins can serve as discriminating parameters. METHODS:
      Patients with chronic rejection (N= 19) and chronic CsA toxicity (N= 17) were
      selected by clinical and histologic criteria. Protocol biopsies without
      histologic abnormalities, taken at 6 months after transplantation from patients
      receiving CsA, were used as controls (N= 6). Total RNA was extracted from the
      renal biopsy tissue, and mRNA levels of transforming growth factor-beta (TGF
      beta) and the extracellular matrix (ECM) molecules collagen Ialpha1, IIIalpha1,
      IValpha3, decorin, fibronectin, and laminin beta2 were measured by real-time
      polymerase chain reaction (PCR). RESULTS: In both patient groups, the mean
      collagen IValpha3 and fibronectin mRNA levels were significantly elevated
      compared to those in controls, whereas only in CsA toxicity were the laminin
      beta2 and TGF-beta mRNA levels significantly increased. The increase of laminin
      beta2 and TGF-beta mRNA levels was significantly higher in the CsA toxicity group
      than in the chronic rejection group (P < 0.001 and P= 0.004, respectively).
      Receiver-operating characteristic (ROC) curve analysis showed that with a 15.6
      fold increase in laminin beta2 mRNA expression as cut-off point, the presence of
      CsA toxicity could be predicted with an 87% sensitivity and an 88% specificity.
      CONCLUSION: Renal laminin beta2 and TGF-beta mRNA levels can be used to
      differentiate between chronic rejection and chronic CsA toxicity in renal
      transplants. The method of mRNA quantification might be applicable as an
      additional diagnostic tool in clinical practice.

PMID- 15496178
TI  - Screening for depression in hemodialysis patients: associations with diagnosis,
      treatment, and outcomes in the DOPPS.
AB  - BACKGROUND: Depressive symptoms and depression are the most frequent psychologic
      problems reported by hemodialysis patients. We assessed the prevalence of
      depressive symptoms and physician-diagnosed depression, their variations by
      country, and associations with treatment by antidepressants among hemodialysis
      patients. We also assessed whether depressive symptoms were independently
      associated with mortality, hospitalization, and dialysis withdrawal. METHODS: The
      sample was represented by 9382 hemodialysis patients randomly selected from
      dialysis centers of 12 countries enrolled in the Dialysis Outcomes and Practice
      Patterns Study (DOPPS II). Depressive symptoms were assessed by the short version
      of the Center for Epidemiological Studies Depression Screening Index (CES-D),
      using > or =10 CES-D score as the cut-off value. RESULTS: Overall prevalence of
      physician-diagnosed depression was 13.9%, and percentage of CES-D score > or =10
      43.0%. While the smallest prevalence of physician-diagnosed depression was
      observed in Japan (2.0%) and France (10.6%), the percentage of CES-D score > or
      =10 in these counties was similar to the whole sample. Patients on
      antidepressants also varied by country, 34.9% and 17.3% among those with
      physician-diagnosed depression and CES-D scores > or =10, respectively. In Cox
      models adjusted for several comorbidities, CES-D scores > or =10 were associated
      with significantly higher relative risks (RR) of death (RR = 1.42; 95% CI = 1.29
      to 1.57), hospitalization (RR = 1.12; 95% CI = 1.03 to 1.22), and dialysis
      withdrawal (RR = 1.55; 95% CI = 1.29 to 1.85). CONCLUSION: The data suggest that
      depression is underdiagnosed and undertreated among hemodialysis patients. CES-D
      can help identify hemodialysis patients who are at higher risk of death and
      hospitalization. Interventions should target these patients with the goal to
      improve survival and reduce hospitalizations.

PMID- 15496179
TI  - Uremic malnutrition is a predictor of death independent of inflammatory status.
AB  - BACKGROUND: Several studies have pointed out the influence of nutritional
      parameters and/or indices of inflammation on morbidity and mortality. Often,
      these conditions coexist, and the relative importance of poor nutritional status
      and chronic inflammation in terms of predicting clinical outcomes in chronic
      hemodialysis (CHD) patients has not been clarified. METHODS: We undertook a
      prospective cohort study analyzing time-dependent changes in several established
      nutritional and inflammatory markers, and their influence on mortality in 194 CHD
      patients (53% male, 36% white, 30% with diabetes mellitus, mean age 55.7 +/- 15.4
      years) throughout a 57-month period. Serial measurements of serum concentrations
      of albumin, prealbumin, creatinine, transferrin, cholesterol, and C-reactive
      protein (CRP), as well as normalized protein catabolic rate, postdialysis weight,
      and phase angle and reactance by bioelectrical impedance analysis were performed
      every 3 months. Clinical outcomes were simultaneously assessed using indicators
      of mortality. RESULTS: Serum albumin, serum prealbumin, serum creatinine, and
      phase angle were significant predictors of all-cause mortality, even after
      adjustment for serum CRP concentrations. Serum CRP concentrations were not
      significantly associated with mortality. Serum albumin concentrations and phase
      angle were also independent predictors of cardiovascular deaths in the
      multivariate model. CONCLUSION: The nutritional status of CHD patients predicts
      mortality independent of concomitant presence or absence of inflammatory
      response. Prevention of, and timely intervention to treat uremic malnutrition by
      suitable means are necessary independent of the presence and/or therapy of
      inflammation in terms of improving clinical outcomes in CHD patients.

PMID- 15496180
TI  - Inhibition of neointimal hyperplasia in vascular grafts by sustained perivascular
      delivery of paclitaxel.
AB  - BACKGROUND: Neointimal hyperplasia occurs commonly at the anastomoses of
      arteriovenous grafts for chronic hemodialysis, causing stenosis and occlusion.
      Antiproliferative drugs may be effective in inhibiting hyperplasia, but local
      drug delivery would be required to minimize systemic side effects. We examined
      the feasibility of local drug delivery to inhibit neointimal hyperplasia at
      dialysis grafts in a canine model. METHODS: Bilateral polytetrafluoroethylene
      loop grafts (10-cm length and 6-mm internal diameter) were placed between the
      femoral artery and ipsilateral femoral vein of five mongrel dogs. At the time of
      surgery or 1 to 5 weeks later, 2 mL of a thermosensitive biodegradable copolymer
      (ReGel) mixed with 0.26 mg or 0.65 mg paclitaxel were applied to the external
      surface of one graft around the anastomoses to provide a depot for sustained
      release of the drug. ReGel alone without paclitaxel was applied to the
      contralateral graft as a control. The grafts and the connecting vessels were
      explanted at eight or nine weeks, and the cross-sections were examined
      histologically. The degree of hyperplasia at the anastomoses was graded by five
      blinded independent reviewers, with scores ranging from 0 to 5. RESULTS: The
      median (25th-75th percentile) hyperplasia score of both arterial and venous
      anastomoses was 1.80 (0.90-3.05) in the grafts treated with ReGel alone, and 0.95
      (0.70-1.50) in the grafts treated with ReGel/paclitaxel (N= 8; P < 0.05 by
      Wilcoxon signed rank test). There were no noticeable localized or systemic
      complications attributed to the treatments in these animals. Paclitaxel levels in
      the plasma obtained from forelimb veins were undetectable (<10 ng/mL).
      CONCLUSION: These results suggest that the local delivery of antiproliferative
      agents using a thermosensitive, injectable biodegradable copolymer (ReGel) for
      sustained delivery is a promising strategy to inhibit neointimal hyperplasia of
      arteriovenous hemodialysis grafts.

PMID- 15496181
TI  - Long-term follow-up study on bone mineral density and fractures after
      simultaneous pancreas-kidney transplantation.
AB  - BACKGROUND: In type 1 diabetic patients with end-stage renal failure, low bone
      mass is prevalent and the incidence of fractures high after simultaneous pancreas
      kidney transplantation (SPK). Data are scarce on preexisting skeletal morbidity
      or the long-term effects of SPK on bone mass and risk of fractures. METHODS: We
      conducted a prospective study addressing these issues in 19 consecutive SPK
      recipients before and at 3, 6, and 12 months, and 2.5 to 4 years after
      establishment of graft function. RESULTS: Prior to transplantation, 13 patients
      (68%) had hyperparathyroidism, 7 of whom had osteoporosis. Mean bone mineral
      density (BMD) was significantly lower at the femoral neck than at the lumbar
      spine (T-scores -2.0 +/- 0.89 vs. -0.66 +/- 0.84). There was a significant
      decrease in BMD at both lumbar spine and femoral neck at 6 months post
      transplantation (-6.0 +/- 5.4% and -6.9 +/- 4.3%, respectively). No further loss
      was observed in the following 6 months. At 1 year post-transplantation, 9
      patients had osteoporosis associated with hyperparathyroidism in 8, and none had
      sustained a clinical fracture. A significant albeit small increase in BMD was
      observed 6 months after start of alfacalcidol 0.25 microg/day. At end-evaluation,
      osteoporosis and hyperparathyroidism persisted in the patients in whom it was
      documented at 1 year. Five patients who had lower BMD at the femoral neck
      pretransplantation sustained a clinical fracture. CONCLUSION: Cortical
      osteoporosis is prevalent in SPK recipients at the time of transplantation,
      progresses early post-transplantation, and is associated with relatively high
      incidence of fractures. Reversal of persistent hyperparathyroidism with the use
      of alfacalcidol may contribute to a decrease in skeletal morbidity.

PMID- 15496182
TI  - Measurement of dialyzer clearance, dialysis time, and body size: death risk
      relationships among patients.
AB  - BACKGROUND: Urea pharmacokinetic equation systems have contributed to better
      understanding of treatment dose among hemodialysis patients. The methods are
      indirect, however, and require the measurement of blood urea nitrogen (BUN)
      concentration before and after a dialysis session to estimate the total treatment
      dose that clinicians prescribe [urea clearance x dialysis time (Kt)] indexed to
      an estimate of body size [the volume of urea distribution in the body (V)]
      yielding the ratio, Kt/V. New technology permits direct on-line measurement of
      average small molecule clearance (Kecn) during each dialysis treatment that can
      be multiplied by time (t) to give a direct measurement of total treatment dose
      (Kt). This study evaluated the relationship of measured Kt with death risk. It
      also evaluated the relationship of simple body size measures to risk and also the
      combination of one such measure [body surface area (BSA)] with Kt to death risk.
      METHODS: The data were taken from the Fresenius Medical Care (NA) (FMCNA)
      clinical database that included patients who had outcome data, height and weight
      measurements, and at least one average Kecn and t measurement during April 2002.
      Kecn, t, and the body size measures [body weight, body mass index (BMI), and
      BSA)] were averaged during the month. Those values were used as predictors of
      survival during the next 1 year in unadjusted and case mix adjusted proportional
      hazards (Cox) models. RESULTS: Increasing values of Kecn, t, Kt and all of the
      body size measures were associated with lower death risk. The body size measure
      most closely associated with risk was the BSA that was used in subsequent models.
      Kt and BSA were independent risk predictors. There was a significant interaction
      between Kt and BSA in the case mix but not the unadjusted model indicating that
      the risk burden of lower total dialysis dose, Kt, may be greater among small than
      large patients. CONCLUSION: The direct measurement of dialysis dose during each
      treatment is practical and the values reported by it are clinically relevant.
      Higher dose was associated with better survival in both small and large patients
      treated three times weekly. Furthermore, smaller patients may require
      proportionately greater total dose than larger patients to achieve comparable
      survival.

PMID- 15496183
TI  - Albumin turns on a vicious spiral of oxidative stress in renal proximal tubules.

PMID- 15496185
TI  - Phosphate intake and the CARE study.

PMID- 15496187
TI  - Using the right MDRD equation.

PMID- 15496189
TI  - Pathophysiology of ANCA-associated vasculitis: are ANCA really pathogenic? A note
      of caution.

PMID- 15496190
TI  - Bioimpedance vector migration up to three days after the hemodialysis session.

PMID- 15496191
TI  - End-stage renal disease increases plasma transcobalamin and neutralizes influence
      of TCN 776C>G polymorphism.

PMID- 15496193
TI  - Microinflammation versus inflammation in chronic renal failure patients.

PMID- 15496194
TI  - Diabetic nephropathy: Linking histology, cell biology, and genetics.

PMID- 15496196
TI  - Tetraspanin microdomains in immune cell signalling and malignant disease.
AB  - A contemporary goal of researchers in leucocyte signalling has been to uncover
      how cells physically organize and compartmentalize signalling molecules into
      efficient, regulated signalling networks. This work has revealed important roles
      of membrane microdomains that are characterized by their distinctive protein and
      lipid compositions. Recent studies have demonstrated that besides typical
      cholesterol- and glycosphingolipid-enriched 'rafts', leucocyte membranes are
      equipped with a different type of microdomain, made up of tetraspanin proteins.
      Tetraspanin proteins are involved in the organization of tetraspanin-enriched
      microdomains by virtue of their capacity to specifically associate with key
      molecules, including integrins, leucocyte receptors and signalling proteins. The
      aspects of leucocyte function influenced by tetraspanin microdomains include
      adhesion, proliferation and antigen presentation. However, the mechanisms by
      which tetraspanin complexes link to intracellular signalling pathways, are still
      largely unknown. This review discusses how tetraspanin microdomains might
      function to regulate signalling in lymphoid and myeloid cells, and how they
      relate to lipid rafts. In addition, we discuss new insights into the role of
      tetraspanins in malignant disease.

PMID- 15496197
TI  - Integration of microsatellite characteristics in the MHC region: a literature and
      sequence based analysis.
AB  - Reviews of microsatellite markers in the human leukocyte antigen region have been
      very useful in addressing the needs of the immunogenetics community.
      Nevertheless, characterization of the same microsatellite loci in different
      laboratories can lead to seemingly contradictory results, particularly in terms
      of nomenclature. Here we provide an update of previous reports, as well as a
      standardized characterization of primers for microsatellites located within the
      major histocompatibility complex (MHC). A uniform and extended inventory of 378
      primer pairs from published reports was performed as well as a standardized
      characterization of the corresponding microsatellite loci according to the
      extended full-length consensus sequence of MHC region. The literature-based
      approach was complemented by a sequence-based analysis of each reported
      microsatellite locus. Iterative electronic polymerase chain reaction runs and an
      original algorithm that characterizes patterns of repeats within sequence were
      used. The sequence of primers was corrected according to the consensus sequence.
      Table of synonymous names for individual microsatellite loci is provided.

PMID- 15496198
TI  - Assign 2.0: software for the analysis of Phred quality values for quality control
      of HLA sequencing-based typing.
AB  - As improvements to DNA sequencing technology have resulted in increasing the
      throughput of DNA sequencing, the bottleneck for high throughput DNA sequencing
      based typing (SBT) has shifted to sequence analysis, genotyping and quality
      control (QC). Consistent high-quality DNA sequence is required in order to reduce
      manual verification and editing of sequence electropherograms. However,
      identifying systematic changes in quality is difficult to achieve without the aid
      of sophisticated sequence analysis programs dedicated to this purpose. We
      describe a computer software program called Assign 2.0, which integrates sequence
      QC analysis and genotyping in order to facilitate high-throughput SBT. Assign 2.0
      performs an analysis of Phred quality values in order to produce quality scores
      for a sample and a sequencing run. This enables sample-to-sample and run-to-run
      QC monitoring and provides a mechanism for the comparison of sequence quality
      between various genes, various reagents and various protocols with the aim of
      improving the overall quality of DNA sequence data. This, in turn, will result in
      reducing sequence analysis as a bottleneck for high-throughput SBT.

PMID- 15496199
TI  - Characterization and functional study of five novel monoclonal antibodies against
      human OX40L highlight reverse signalling: enhancement of IgG production of B
      cells and promotion of maturation of DCs.
AB  - OX40 ligand (OX40L), a molecule originally identified as human gp34, is an
      important co-stimulatory molecule during immune response. In this study, we
      report on five functional mouse anti-human OX40L monoclonal antibodies named as
      9H10, 4C12, 8D10, 4H4 and 1G1, characterized by means of flow cytometry, Western
      blot and competition assay. These monoclonal antibodies bound to distinct OX40L
      epitopes on activated B cells and dendritic cells (DCs) and two of them could
      suppress the proliferation of T lymphocytes co-stimulated by mature DCs.
      Furthermore, we demonstrated that our monoclonal antibodies, such as 9H10 and
      4C12, could trigger OX40L reverse signal that enhanced IgG production of B cells
      and promoted maturation of DCs as evidenced by the upexpression of CD80, CD86,
      CD83 and CXCR4 and monoclonal antibody 9H10 could also promote anti-CD40
      monoclonal-antibody-stimulated DCs in order to induce T cells to secrete more
      interleukin-2 and interferon-gamma, which suggested that OX40L signals could
      strengthen the effect of CD40 signals on promoting Th1 differentiation.

PMID- 15496200
TI  - Two major histocompatibility complex haplotypes influence susceptibility to
      sporadic inclusion body myositis: critical evaluation of an association with HLA
      DR3.
AB  - Previous studies of sporadic inclusion body myositis (sIBM) have shown a strong
      association with HLA-DR3 and other components of the 8.1 ancestral haplotype (AH)
      (HLA-A1, B8, DR3), where the susceptibility locus has been mapped to the central
      major histocompatibility complex (MHC) region between HLA-DR and C4. Here, the
      association with HLA-DR3 and other genes in the central MHC and class II region
      was further investigated in a group of 42 sIBM patients and in an ethnically
      similar control group (n = 214), using single-nucleotide polymorphisms and
      microsatellite screening. HLA-DR3 (marking DRB1*0301 in Caucasians) was
      associated with sIBM (Fisher's test). However, among HLA-DR3-positive patients
      and controls, carriage of HLA-DR3 without microsatellite and single-nucleotide
      polymorphism alleles of the 8.1AH (HLA-A1, B8, DRB3*0101, DRB1*0301, DQB1*0201)
      was marginally less common in patients. Patients showed no increase in carriage
      of the 18.2AH (HLA-A30, B18, DRB3*0202, DRB1*0301, DQB1*0201) or HLA-DR3 without
      the central MHC of the 8.1AH, further arguing against HLA-DRB1 as the direct
      cause of susceptibility. Genes between HLA-DRB1 and HOX12 require further
      investigation. BTL-II lies in this region and is expressed in muscle. Carriage of
      allele 2 (exon 6) was more common in patients. BTL-II(E6)*2 is characteristic of
      the 35.2AH (HLA-A3, B35, DRB1*01) in Caucasians and HLA-DR1, BTL-II(E6)*2,
      HOX12*2, RAGE*2 was carried by several patients. The 8.1AH and 35.2AH may confer
      susceptibility to sIBM independently or share a critical allele.

PMID- 15496201
TI  - Molecular analysis of HLA allele frequencies and haplotypes in Baloch of Iran
      compared with related populations of Pakistan.
AB  - The extreme polymorphism in different loci of the human leukocyte antigen (HLA)
      system has been used as an invaluable tool for anthropological studies.
      Determination of HLA allele and haplotype frequencies in different ethnic groups
      is useful for population genetic analyses and the study of genetic relationships
      among them. In the present study, molecular analysis of HLA-A, -B, -C, -DQA1, 
      DQB1, and -DRB1 genes has been used to assign HLA allele and haplotype
      frequencies in 100 unrelated healthy individuals from the Baloch ethnic group of
      Iran. The results were compared with Baloch and other ethnic groups in the
      neighboring Pakistan. The results of this study showed that the most frequent HLA
      class I alleles were A*02011 (20.2%), B*4006 (11.1%), and C*04011 (28.6%). The
      most common HLA class II alleles were DQA1*0101/2 (42.5%), DQB1*0201 (32%), and
      DRB1*0301 (29%). Three-locus haplotype analysis revealed that A*11011-B*4006
      C*15021 (5.8%) and DQA1*0501-DQB1*0201-DRB1*0301 (22.1%) were the most common HLA
      class I and II haplotypes, respectively, in this population. Neighbor-joining
      tree based on DA genetic distances and correspondence analysis according to HLA
      A, -B, -DQB1, and -DRB1 allele frequencies showed that Baloch of Iran are
      genetically very close to Baloch and Brahui of Pakistan. This may reflect an
      admixture of Brahui and Baloch ethnic groups of Pakistan in the Balochistan
      province of Iran.

PMID- 15496202
TI  - HLA-E polymorphism in patients with nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma (NPC) has been known to be associated with HLA class I
      region. The aim of this study was to investigate the association between HLA-E
      and genetic susceptibility to nasopharyngeal carcinogenesis by comparing the
      frequencies of HLA-E alleles in 100 Thai NPC patients and 100 healthy controls.
      HLA-E typing was performed by means of polymerase chain reaction-sequence
      specific oligonucleotide probe method. The frequency of the HLA-E*0103 allele and
      HLA-E*0103, 0103 genotype, but not others, was increased in NPC patients,
      compared to controls. This observation suggests a possible role for HLA-E in NPC
      development, possibly via natural killer cell or cytotoxic lymphocyte function.

PMID- 15496203
TI  - Genetic analysis of the CD28/CTLA4/ICOS (CELIAC3) region in coeliac disease.
AB  - In order to extend our previous findings of genetic linkage to the
      CD28/CTLA4/ICOS region on chromosome 2q33 (CELIAC3) in coeliac disease (CD), we
      have investigated 22 genetic markers in 325 Norwegian/Swedish multiplex and
      simplex CD families. We found both linkage and association with several markers,
      primarily in the multiplex material. We observed strong linkage disequilibrium
      (LD) between SNPs (Single Nucleotide Polymorphisms) within an LD block delimited
      by MH30 and D2S72. A haplotype of this region marked by the alleles -1147*T: +
      49*A:CT60*G:CT61*A was significantly associated with CD, suggesting that one or
      more polymorphisms of this haplotype, possibly -1147*T, are involved in CD
      susceptibility. The CT60 SNP, a polymorphism found to be most strongly associated
      with some other immune-mediated diseases, was not associated with CD, as this SNP
      was part of both associated and non-associated haplotypes. Moreover, our results
      suggest that CELIAC3 harbours several independent loci contributing to CD
      susceptibility.

PMID- 15496204
TI  - Assessment of synthetic peptides of severe acute respiratory syndrome coronavirus
      recognized by long-lasting immunity.
AB  - In order to determine highly immunogenic severe acute respiratory syndrome
      coronavirus (SARS-CoV) epitope peptides capable of inducing long-lasting
      immunity, we first screened immunoglobulin-G (IgG) antibodies reactive to 197
      different overlapping 15-mers from the SARS-CoV proteins in the sera of three
      infected patients. Forty-two peptides among them were reactive to the sera from
      all three patients. Consequently, we tested for the reactivity of these 42
      peptides to patients' sera (n = 45) at 6-month post-infection. The significantly
      higher levels of IgG antibodies specific to three (S791, M207 and N161) of 42
      peptides were detectable in the post-infection sera from 23 (51%), 27 (60%) and
      19 (42%) of 45 patients, respectively. These three peptides, recognized by their
      long-lasting immunity, may provide a better understanding of the immunogenicity
      of SARS-CoV.

PMID- 15496205
TI  - HLA-B*8102*, a new allele found in an external proficiency testing scheme.
AB  - A new human leukocyte allele HLA-B*8102 has been identified in a cell provided by
      the UCLA International Cell Exchange scheme. The nucleotide sequences of exons 2
      and 3 of the new allele are identical with HLA-B*8101. Four nucleotide
      differences, however, are observed in exon 1, three of them representing non
      synonymous base changes.

PMID- 15496206
TI  - High frequency of QPY allele and linkage disequilibrium of granzyme-B in Epstein
      Barr-virus-associated hemophagocytic lymphohistiocytosis.
AB  - Mediation of Epstein-Barr virus (EBV)-specific cytotoxicity in T lymphocyte via
      the perforin/granzyme pathway has been demonstrated; therefore, a study involving
      cytolytic molecules was essential for the clarification of hemophagocytic
      lymphohistiocytosis (HLH) pathogenesis. This investigation, which analysed the
      frequency of three allelic mutations of granzyme-B (55Q/R, 95P/A and 247Y/H) in
      patients with EBV-HLH and infectious mononucleosis, identified the high
      prevalence of the QPY haplotype in EBV-HLH patients in comparison with healthy
      controls. A > G polymorphism was also detected in intron 5; furthermore, nearly
      complete linkage disequilibrium was observed among these polymorphisms. The
      recessive role of the QPY haplotype of granzyme-B might be responsible for the
      pathogenesis of EBV-HLH. Cytotoxicity and DNA fragmentation of cytotoxic T
      lymphocytes did not differ among patients characterized by the QPY/QPY, RAH/RAH
      and QPY/RAH genotypes. This finding suggested that DNA fragmentation in target
      cells is mediated not only by granzyme-B but also by other molecules, including
      other granzymes or Fas.

PMID- 15496207
TI  - Description of a novel HLA-B allele, B*5613, identified during HLA-typing using
      sequence-specific oligonucleotide hybridization and sequence-specific
      amplification.
AB  - Here, we report on the characterization of a novel human leukocyte antigen (HLA)
      B allele, B*5613. The allele was identified in an adult male from North Africa
      who was suffering from sickle cell anemia. HLA-B*5613 most closely matches to
      B*5601 differing only by a substitution of three nucleotides of codon 180. Due to
      this substitution, low-resolution HLA-typing using sequence-specific
      oligonucleotide hybridization or amplification using sequence-specific primers
      gave inconclusive results. DNA sequencing confirmed a variation of codon 180 (CTG
      ->GAC) resulting in an amino acid substitution Leu156Asp.

PMID- 15496208
TI  - Characterization of a novel HLA-DQB1 allele, DQB1*020102.
AB  - A novel human leukocyte antigen (HLA)-DQB1 allele, DQB1*020102, was detected in a
      28-year-old woman of Han ethnic in Guangzhou, China. Compared with HLA
      DQB1*020101 and HLA-DQB1*0202, they differed in only one nucleotide at the
      position 167 (C to T) of exon 2, which was a highly conserved position. This is a
      synonymous mutation, which does not cause any change in the amino acid sequence
      of mature protein.

PMID- 15496209
TI  - Three new DRB alleles routinely identified by sequence-based typing: DRB1*010103,
      DRB1*0326 and DRB3*0219.
AB  - We describe here two additional DRB1 alleles found in two Caucasoid recipient
      candidates for organ transplant and a new DRB3 allele found in a Caucasoid
      unrelated bone marrow donor from the German file. HLA-DRB generic and allele
      typing were performed using commercial kits, subsequently exon 2 was sequenced.
      We found a DRB1*010101 with a silent mutation at codon 68 and a DRB1*0306 with a
      mutation at codon 38 (T-C) which causes an amino acid substitution from Val to
      Ala. DRB3*0219 differs from DRB3*020201 by two-point mutations at codons 60 and
      74 (A/C and A/G, respectively). These mutations at positions 266 and 308 were
      responsible for two amino acid substitutions (Tyr to Ser and Gln to Arg).

PMID- 15496210
TI  - Characterization of a new HLA-DRB1*01 allele (HLA-DRB1*010203) in a Caucasian
      Italian family by using sequence-based typing.
AB  - We report the identification of an HLA-DRB1*01 nucleotide sequence variant in
      three members of a Caucasian Italian family by using sequence-based typing. The
      nucleotide sequence of exon 2 observed in the new allele is identical to that of
      HLA-DRB1*010201 except in position 189 (codon 34) where the adenine of the
      consensus was replaced by a guanine and it was designated officially as HLA
      DRB1*010203* by the WHO Nomenclature Committee.

PMID- 15496211
TI  - Nomenclature for factors of the HLA system, update July 2004.

PMID- 15496213
TI  - Review article: the pharmacodynamics and pharmacokinetics of proton pump
      inhibitors--overview and clinical implications.
AB  - During the past two decades, enormous changes occurred in the management of
      gastric acid-related diseases. First, the histamine2-receptor antagonists were
      introduced, offering patients the first single-agent therapy that effectively
      reduced gastric acid secretion. Proton pump inhibitors became widely available in
      the early 1990s, and they generally appeared to be superior to the histamine2
      receptor antagonists in acid-suppressing activity, symptom control and healing.
      Most physicians now use proton pump inhibitors as first-line treatment for many
      patients with acid-peptic disorders, including erosive gastro-oesophageal reflux
      disease (GERD), nonerosive reflux disease (NERD) and duodenal and gastric ulcers.
      Although proton pump inhibitors are often thought to be interchangeable, some
      differences have emerged in their pharmacological properties, which may be
      reflected in some aspects of clinical efficacy. Such differences include potency,
      speed of onset and duration of pH 'holding times'. Helicobacter pylori has now
      been recognized as an important factor in the pathogenesis of acid-peptic
      disorders. It is clear that H. pylori eradication can dramatically reduce the
      chronicity of gastric and duodenal ulcers, and accepted therapeutic regimens for
      H. pylori eradication now include proton pump inhibitors and two or more
      antibiotics. Although all accepted proton pump inhibitor-based 'triple therapies'
      are roughly equivalent in efficacy, there is now a shortened regimen available
      that will potentially enhance compliance and decrease cost. This review examines
      the relative advantages of proton pump inhibitors vs. histamine2-receptor
      antagonists in the context of acid suppression and in various gastric acid
      related diseases. A brief overview presents the pharmacodynamics and
      pharmacokinetics of the proton pump inhibitors with particular attention paid to
      rabeprazole, one of the newer drugs in its class.

PMID- 15496215
TI  - Review article: relief of symptoms in gastric acid-related diseases--correlation
      with acid suppression in rabeprazole treatment.
AB  - Symptom relief is one of the key goals in the management of gastric acid-related
      disorders such as gastro-oesophageal reflux disease (GERD), including nonerosive
      reflux disease (NERD), and duodenal and gastric ulcer. Whereas heartburn and
      regurgitation are classic symptoms of GERD, duodenal and gastric ulcers are
      associated with epigastric pain. The relationship between gastric acid and the
      presence of symptoms correlates well in GERD and duodenal ulcer, but not in
      gastric ulcer and NERD. Nevertheless, in all these disorders, gastric acid is
      considered a key pathogenic element, and acid suppression remains central to
      therapy. With their profound, prolonged effect on acid inhibition, proton pump
      inhibitors are considered the first-choice therapy for these disorders.
      Rabeprazole is a newer generation proton pump inhibitor that suppresses the
      gastric proton pump and acid secretion more rapidly than does omeprazole,
      lansoprazole or pantoprazole. In clinical trial settings, rabeprazole provided
      fast and sustained symptom relief, which can help ensure patient acceptance of
      therapy and aid in patient compliance.

PMID- 15496214
TI  - Review article: relationship between the metabolism and efficacy of proton pump
      inhibitors--focus on rabeprazole.
AB  - Proton pump inhibitors are now considered the mainstay of treatment for acid
      related disease. Although all proton pump inhibitors are highly effective, the
      antisecretory effects of different drugs in this class are not completely
      consistent across patients. One reason for this is the acid-suppressing effect of
      Helicobacter pylori infection, which may augment the actions of proton pump
      inhibitors. A second important reason for interpatient variability of the effects
      of proton pump inhibitors on acid secretion involves genetically determined
      differences in the metabolism of these drugs. This article focuses on the impact
      of genetic polymorphism of cytochrome P450 (CYP)2C19 on the pharmacokinetics and
      pharmacodynamics of proton pump inhibitors, particularly rabeprazole. Results
      reviewed indicate that the metabolism and pharmacokinetics of rabeprazole differ
      significantly from those of other proton pump inhibitors. Most importantly, the
      clearance of rabeprazole is largely nonenzymatic and less dependent on CYP2C19
      than other drugs in its class. This results in greater consistency of
      pharmacokinetics for rabeprazole across a wide range of patients with acid
      related disease, particularly those with different CYP2C19 genotypes. The
      pharmacodynamic profile for rabeprazole is also characterized by more rapid
      suppression of gastric acid secretion than with other proton pump inhibitors,
      which is also independent of CYP2C19 genotype. The favourable
      pharmacokinetic/pharmacodynamic profile for rabeprazole has been shown to result
      in high eradication rates for H. pylori in both normal and poor metabolizers.
      Pharmacodynamic results have also suggested that rabeprazole may be better suited
      than omeprazole as on-demand therapy for symptomatic gastro-oesophageal reflux
      disease. Finally, the use of rabeprazole is not complicated by clinically
      significant drug-drug interactions of the type that have been reported for
      omeprazole.

PMID- 15496216
TI  - Review article: pH, healing and symptom relief with rabeprazole treatment in acid
      related disorders.
AB  - Control of gastric acid secretion by antisecretory agents has been the
      cornerstone of therapy in the successful management of all acid-related
      disorders, including gastro-oesophageal reflux disease (GERD), and duodenal and
      gastric ulcer. Treatment efficacy has been strongly correlated with degree and
      duration of acid suppression within the 24-h period and with total duration of
      therapy. All proton pump inhibitors are highly effective for the healing of
      ulcers and erosive oesophagitis. All have closely similar mechanisms of action,
      yet important pharmacological differences exist, which can significantly impact
      certain aspects of their clinical efficacy. Rabeprazole's rapid activation over a
      wide pH range may be the explanation for its early onset of effective acid
      inhibition compared with other proton pump inhibitors such as omeprazole,
      lansoprazole and pantoprazole. Like rabeprazole, esomeprazole is also a potent
      inhibitor of gastric acid at steady state, although it is thought that
      rabeprazole may provide enhanced first-day acid suppression compared with
      esomeprazole. First-day antisecretory efficacy should produce faster symptom
      relief, a hypothesis supported by clinical data. Moreover, drugs with
      pharmacological profiles that include both rapid onset and potent antisecretory
      effects should help control healthcare costs by reducing the need for otherwise
      commonly used twice-daily proton pump inhibitor administration.

PMID- 15496217
TI  - The safety and tolerability of donepezil in patients with Alzheimer's disease.
AB  - Cholinesterase (ChE) inhibitors, which prevent the hydrolysis of acetylcholine,
      have been approved for the symptomatic treatment of Alzheimer's disease (AD) for
      over a decade. However, the first ChE inhibitors were associated with a high
      incidence of side-effects and general tolerability concerns, including
      hepatotoxicity. Side-effects associated with increased cholinergic activity,
      particularly in the gastrointestinal (GI) system, can prevent patients from
      achieving effective doses of drug. In addition, the advanced age and frail nature
      of patients with AD mean that poor tolerability is a serious concern. The
      potential for drug-drug interactions is also an important consideration, due to
      the high prevalence of comorbid disease in these patients. Data both from
      clinical trials and studies in routine clinical practice have shown that
      donepezil is associated with a low incidence of GI adverse events (AEs) that is
      comparable with placebo. Donepezil is a potent, selective inhibitor of
      acetylcholinesterase, and selective inhibition of central as opposed to
      peripheral ChEs might be expected to reduce the incidence of AEs, thus this may
      explain the lower incidence of cholinergic AEs observed following treatment with
      donepezil, compared with nonselective ChE inhibitors. There are no differences in
      cardiovascular AEs, including bradycardia, between placebo and donepezil groups
      in the clinical trials published to date, even in a very sick vascular dementia
      population with high rates of comorbidity and concomitant medication use. Data
      from single- and multiple-dose studies of donepezil in patients with hepatic
      impairment and with moderately to severely impaired renal function indicate that
      donepezil is safe and well tolerated in these groups. Furthermore, both in vitro
      and clinical studies have shown that donepezil is not associated with drug-drug
      interactions. The incidence of weight loss is very similar between donepezil- and
      placebo-treated patients. Although insomnia and other sleep disorders have been
      reported following administration of donepezil, lengthening the time period
      before increasing the dose of donepezil from 5 to 10 mg day(-1) or switching to
      morning dosing can reduce these events to the levels of placebo-treated patients.
      Over 770 million days of patient use and an extensive publication database
      demonstrate that donepezil has a good tolerability and safety profile.

PMID- 15496218
TI  - Steady-state pharmacokinetics, pharmacodynamics and tolerability of donepezil
      hydrochloride in hepatically impaired patients.
AB  - AIMS: To evaluate the pharmacokinetics (PK), pharmacodynamics (PD), tolerability
      and safety of donepezil HCl 5 mg following oral doses for 1 and 24 days in
      hepatically impaired patients compared with healthy controls under steady-state,
      multiple-dose conditions. METHODS: In this single-centre, multiple-dose, open
      label study, patients with impaired hepatic function (Child-Pugh grade A or B)
      and healthy controls (matched by gender, age and weight to the hepatically
      impaired patients) received a single 5 mg dose of donepezil on day 1 and then
      donepezil HCl 5 mg once daily from days 6 to 29. PK and PD (determination of
      erythrocyte acetylcholinesterase inhibition) parameters were evaluated on days 1
      and 29. Treatment-emergent adverse events (AEs), vital signs, physical
      examination and clinical laboratory test parameters were monitored throughout the
      study. RESULTS: A total of 35 subjects (18 patients with hepatic impairment and
      17 healthy controls) were enrolled and 32 subjects (16 in each group) completed
      the study. On day 1 (following a single dose) hepatically impaired patients
      showed a significant decrease in T(max), while t((1/2)) and AUC(0-infinity) were
      significantly increased compared with the healthy controls. On day 29 (following
      multiple doses), AUC(0-24 h), C(max), t((1/2)), C(SS), and R(A) were
      significantly increased in hepatically impaired patients compared with healthy
      controls. AUC(0-24 h) increased by 47.6% in the patients with hepatic impairment
      compared with the healthy controls. There were no significant differences in PD
      between the groups, although at steady state, the mean AChE inhibition was 16.2%
      higher in the hepatically impaired patients. No serious AEs were reported and no
      subject withdrew from the study due to AEs. The most common AEs in both groups
      were headache and diarrhoea. No clinically significant changes from baseline were
      observed in vital signs, physical examination findings or electrocardiograms.
      There was a significant difference in the number of hepatically impaired subjects
      with abnormalities in serum glucose compared with healthy subjects. However,
      these elevations were not associated with AEs. CONCLUSIONS: The results of this
      study suggest that patients with AD and mild to moderate hepatic impairment
      (Child-Pugh grade A or B) can be safely given donepezil 5 mg once daily and that
      this dose is associated with a nonsignificantly higher AChE inhibition than age
      matched volunteers.

PMID- 15496219
TI  - Steady-state pharmacokinetics and safety of donepezil HCl in subjects with
      moderately impaired renal function.
AB  - AIMS: To characterize the pharmacokinetic, pharmacodynamic and safety profiles of
      donepezil in subjects with moderate renal impairment and matched healthy controls
      during single-dose and multiple-dose phases. METHODS: This open-label study
      enrolled subjects with moderate renal impairment (creatinine clearance [CL(Cr)]
      17-33 ml min(-1) 1.73 m(-2) body surface area) and age, weight and sex-matched
      healthy controls. A single-dose (5 mg donepezil) phase was followed by a 23-day
      multiple dose (5 mg day(-1) donepezil) steady-state phase. The pharmacokinetic
      and pharmacodynamic parameters of donepezil were determined for up to 144 h after
      the first dose and 168 h after the last dose. RESULTS: Thirty-six subjects were
      enrolled, 19 renally impaired and 17 healthy controls. All pharmacokinetic and
      pharmacodynamic parameters were similar between groups after a single dose of
      donepezil (C(max) 5.17 +/- 0.36 and 6.07 +/- 0.49 ng ml(-1); AUC(0-24) 76.05 +/-
      5.54 and 77.45 +/- 4.49 ng.h ml(-1); mean maximum percentage inhibition [I(max)]
      red blood cell (RBC) AChE activity 32.07 +/- 2.00 and 31.69 +/- 2.45%; for
      subjects with renal impairment and healthy subjects, respectively).
      Pharmacokinetic parameters under steady-state conditions did not differ between
      renally impaired and healthy subjects (C(SS) 20.83 +/- 1.78 and 18.38 +/- 1.52 ng
      ml(-1); AUC(0-24) 500.0 +/- 42.8 and 441.1 +/- 36.4 ng.h ml(-1); degree of
      accumulation [R(A)] 6.98 +/- 0.59 and 5.94 +/- 0.53; for subjects with renal
      impairment and healthy subjects, respectively). Main pharmacodynamic parameters
      were also similar in renally impaired and healthy subjects at steady state
      (average percentage inhibition [I(SS)] RBC AChE activity 65.11 +/- 2.52 and 60.62
      +/- 2.95, respectively). Protein binding was also similar between groups (% free
      donepezil 23.54 +/- 1.96 and 20.23 +/- 0.64, respectively). Donepezil was well
      tolerated by both groups. CONCLUSIONS: These results indicate that the
      pharmacokinetics of donepezil are not altered after dosing to steady state, and
      that donepezil can be administered safely to subjects with moderate renal
      impairment.

PMID- 15496220
TI  - Concurrent administration of donepezil HCl and sertraline HCl in healthy
      volunteers: assessment of pharmacokinetic changes and safety following single and
      multiple oral doses.
AB  - AIM: This study evaluated the safety and pharmacokinetics (PK) of donepezil HCl
      and sertraline HCl when administered separately and in combination. METHODS: This
      was a randomized, open-label, three-period crossover study. In consecutive dosing
      periods separated by washout periods of > or = 3 weeks, healthy volunteers
      received either oral donepezil HCI 5 mg once daily for 15 days, oral sertraline
      HCl 50 mg once daily for 5 days followed by 10 days of once-daily sertraline HCl
      100 mg, or the simultaneous administration of oral donepezil HCl and sertraline
      HCl. Plasma donepezil and sertraline concentrations were determined by high
      performance liquid chromatography/mass spectrometry. Safety was evaluated by
      physical and laboratory evaluations and the monitoring of adverse events (AEs).
      RESULTS: A total of 19 volunteers (16 male and three female) were enrolled. Three
      male subjects withdrew from the study prematurely due to AEs (one case of
      nausea/stomach cramps and one case of eosinophilia during combination treatment,
      and one upper respiratory tract infection during treatment with sertraline HCl
      alone). In subjects who completed all three treatment periods (n = 16), the
      concurrent administration of donepezil HCl and sertraline HCl did not alter the
      steady-state (day 15) PK parameters of donepezil HCl. A small (< 12%) but
      statistically significant (P = 0.02) increase in donepezil C(max) was seen after
      single doses of sertraline HCl and donepezil HCl on day 1 but this was not
      thought to be clinically meaningful. No significant differences in the t(max) or
      AUC(0-24 h) of donepezil were observed between the donepezil HCl only or
      donepezil HCl plus sertraline HCl groups on day 1. No significant changes in
      sertraline PK parameters were observed either on day 1 (single dose) or on day 15
      (steady state) when sertraline HCl was co-administered with donepezil HCl.
      Generally, the concurrent administration of donepezil HCl and sertraline HCl was
      well tolerated, with no serious AEs reported during the study. Some digestive
      system AEs tended to occur more frequently during combination treatment than with
      either treatment alone, but there was no statistically significant increase in
      the incidence of any individual AE. The most common AEs during the combination
      therapy were nausea and diarrhoea, which were rated as mild or moderate in
      severity. These AEs were also reported during the administration of each drug
      alone. CONCLUSIONS: The co-administration of once-daily oral donepezil HCl 5 mg
      for 15 days and once-daily oral sertraline HCl (50 mg for 5 days increased to 100
      mg for 10 days) did not result in any clinically meaningful pharmacokinetic
      interactions, and no unexpected AEs were observed.

PMID- 15496221
TI  - Repeated dosing with donepezil does not affect the safety, tolerability or
      pharmacokinetics of single-dose thioridazine in young volunteers.
AB  - AIM: To investigate the effects of donepezil at steady state on the safety,
      tolerability and pharmacokinetics of a single dose of thioridazine, in healthy
      subjects. METHODS: An open, two-way, balanced crossover study, in 12 subjects
      (six men and six women) aged 19-41 years. During both treatment periods, subjects
      received a single oral dose of 50 mg thioridazine; in one period the thioridazine
      was given alone, and in the other period it was given together with the last of
      15 daily, oral doses of donepezil 5 mg. The 'washout' periods were 1 week when
      thioridazine was given first, and 2 weeks when thioridazine was given last.
      Plasma concentrations of thioridazine were measured after each dose, and
      pharmacokinetic parameters were determined. Interactions were tested by using an
      equivalence analysis in which thioridazine was the 'Reference' and thioridazine +
      donepezil the 'Test' regimen. Safety and tolerability were monitored. RESULTS:
      Donepezil had no marked effect on the pharmacokinetics of thioridazine, as judged
      by the equivalence analysis of AUC(0-tn), AUC(0-infinity), t((1/2)) and t(max).
      C(max) was very similar in the 'Test' and 'Reference' regimens, but the
      confidence intervals were too wide to confirm equivalence. Donepezil was well
      tolerated, whereas thioridazine was associated with light-headedness, tiredness
      and postural hypotension, irrespective of whether or not donepezil was given
      concurrently. CONCLUSIONS: Repeated dosing with donepezil, 5 mg daily for 2
      weeks, had no significant effect on the safety, tolerability or pharmacokinetics
      of thioridazine. Thioridazine was poorly tolerated.

PMID- 15496222
TI  - Concurrent administration of donepezil HCl and levodopa/carbidopa in patients
      with Parkinson's disease: assessment of pharmacokinetic changes and safety
      following multiple oral doses.
AB  - AIM: The use of acetylcholinesterase inhibitors for the treatment of comorbid
      Alzheimer's disease in Parkinson's disease (PD) patients stabilized on a levodopa
      regimen may potentially disrupt cholinergic balance. This randomized, double
      blind, crossover study investigated the safety of, and possible drug-drug
      interaction between, donepezil HCl and levodopa/carbidopa. METHODS: Twenty-five
      patients with PD who were taking physician-optimized doses of levodopa/carbidopa
      (with daytime dosing intervals of 4-8 h) were administered once-daily doses of
      either donepezil HCl (5 mg) or placebo for 15 days, in two treatment periods,
      separated by a washout of at least 2 weeks. Some patients took a second dose of
      levodopa/carbidopa after 4 h, therefore subanalysis of the levodopa/carbidopa
      data was conducted up to 4 h and 8 h after dosing. Twenty-six healthy matched
      controls received open-label donepezil HCl only, for a single 15-day period.
      Blood samples were collected before, during and after the 15 doses of donepezil
      HCl for pharmacokinetic (PK) assessments. Pharmacokinetic parameters included
      maximum attained plasma drug concentration (C(max)), time at which C(max) is
      attained (t(max)), plasma drug concentration at steady state (C(ss)), and area
      under the drug concentration-time curve over the dosing interval. Safety
      assessments included monitoring adverse events, and the Unified Parkinson's
      Disease Rating Scale (UPDRS) motor examination. RESULTS: The mean age of all
      subjects was 72.6 +/- 1.3 years. Donepezil PK assessments of PD patients
      receiving levodopa/carbidopa were similar to the PK results from healthy controls
      who received donepezil HCl only (mean AUC(0-12 h)= 281.6 +/- 17.6 and 268.6 +/-
      19.9 ng.h ml(-1), respectively). Carbidopa PK were not significantly altered by
      the concomitant administration of multiple doses of donepezil HCl, compared with
      when PD patients received placebo (mean AUC(0-8 h)= 921.8 +/- 160 and 821.8 +/-
      113 ng.h ml(-1), respectively). Four hours after administration of donepezil HCl
      in PD patients, AUC(0-4 h), C(max) and C(ss) of levodopa were higher than when PD
      patients received placebo (P < 0.05). Eight hours after donepezil HCl, however,
      only C(max) and t(max) were observed to change compared with when PD patients
      received placebo (mean C(max) = 2652 +/- 429 and 2077 +/- 276 ng ml(-1),
      respectively; mean t(max) = 1.7 +/- 0.4 and 2.9 +/- 0.5 h, respectively; P< or =
      0.05). The number of PD patients who experienced at least one adverse event
      during the study (13/25) was higher when they received donepezil HCl than when
      they received placebo (5/25), but was the same as healthy subjects who received
      donepezil HCl only (13/26). There were no significant differences in change from
      baseline on the UPDRS motor examination parameters in PD patients when they took
      donepezil HCl and when they took placebo. CONCLUSIONS: No clinically significant
      drug-drug interactions between donepezil HCl and levodopa/carbidopa were observed
      at steady state. The small changes in the pharmacokinetics of levodopa did not
      result in any change in motor symptoms. Co-administration of the two drugs led to
      a small increase in adverse events compared with administration of
      levodopa/carbidopa alone in PD patients. These adverse events, however, were
      consistent with donepezil's cholinomimetic effect, and their incidence was
      comparable to that observed following the administration of donepezil HCl alone.

PMID- 15496223
TI  - Concurrent administration of donepezil HCl and risperidone in patients with
      schizophrenia: assessment of pharmacokinetic changes and safety following
      multiple oral doses.
AB  - AIM: This open-label, multiple-dose trial investigated the effect of concurrent
      administration of donepezil HCl with risperidone on the pharmacokinetics (PK) and
      safety profiles of both drugs. METHODS: Sixteen male patients with schizophrenia,
      who were receiving stable, physician-optimized risperidone (1-4 mg twice daily),
      and 15 healthy age- and weight-matched male controls, received donepezil HCl 5 mg
      daily for 7 days. Patients with schizophrenia remained on their physician
      optimized dose of risperidone throughout the study. Pharmacokinetic parameters
      (C(max), t(max) and AUC) were assessed from plasma drug concentrations measured
      in blood collected before, during and after administration (for 12 h after
      risperidone on days 0 and 7, and for 24 h after donepezil HCl on day 7). RESULTS:
      The mean age of all the subjects was 38.5 years. Donepezil PK parameters were
      similar between patients taking donepezil HCl + risperidone (AUC(0-24 h) = 329.0
      +/- 17.2 ng x h ml(-1)) and controls taking donepezil HCl alone (AUC(0-24 h) =
      354.7 +/- 28.2 ng x h ml(-1)). Pharmacokinetic parameters for risperidone and 9
      OH risperidone were not altered in patients with schizophrenia after 7 days of
      donepezil HCl administration (AUC(0-12 h) standardized by dose: risperidone =
      59.6 +/- 16.3 ng.h ml(-1) at day 0, 56.0 +/- 15.8 ng x h ml(-1) at day 7; 9-OH
      risperidone = 162.1 +/- 19.2 ng x h ml(-1) at day 0, 163.3 +/- 15.0 ng x h ml(-1)
      at day 7). The most common adverse event in both treatment groups was diarrhoea
      (6/16 risperidone + donepezil HCl patients and 9/16 donepezil HCl only subjects).
      There were no significant changes in physical examination, ECG, vital signs or
      treatment-emergent abnormal laboratory values associated with either of the
      treatment regimens. No subject developed extrapyramidal side-effects following
      donepezil administration. CONCLUSIONS: These results suggest that once-daily
      dosing of 5 mg donepezil HCl does not alter the PK of risperidone in patients
      with schizophrenia. The combination of risperidone and donepezil HCl was well
      tolerated.

PMID- 15496225
TI  - Community effectiveness of chloroquine and traditional remedies in the treatment
      of young children with falciparum malaria in rural Burkina Faso.
AB  - BACKGROUND: There is little information on the effectiveness of modern compared
      to traditional malaria treatment from the rural areas of Africa. METHODS: Follow
      up of 402 episodes of clinical malaria among pre-school children in Nouna Health
      District, northwestern Burkina Faso. The exposure of interest was the type of
      treatment (chloroquine versus traditional); the outcome was clinical response to
      treatment. RESULTS: Out of the 402 observed malaria episodes, 87% were treated
      with chloroquine and 13% with traditional remedies. Overall, community
      effectiveness was 67% with chloroquine and 54% with traditional treatment.
      Chloroquine effectiveness was associated with age and ethnicity. An additional
      interview survey demonstrated wide variations in the dosages of chloroquine given
      to young children in this community. CONCLUSIONS: The effectiveness of
      chloroquine, when used within the community, was significantly lower in this
      study than its known efficacy in the study area. This concerns, in particular,
      the very young children. These findings demonstrate the need for better education
      of parents about correct dosage of first-line malaria drugs, and for particular
      attention in the treatment of very young children.

PMID- 15496226
TI  - Risk factors for acute chemical releases with public health consequences:
      Hazardous Substances Emergency Events Surveillance in the U.S., 1996-2001.
AB  - BACKGROUND: Releases of hazardous materials can cause substantial morbidity and
      mortality. To reduce and prevent the public health consequences (victims or
      evacuations) from uncontrolled or illegally released hazardous substances, a more
      comprehensive analysis is needed to determine risk factors for hazardous
      materials incidents. METHODS: Hazardous Substances Emergency Events Surveillance
      (HSEES) data from 1996 through 2001 were analyzed using bivariate and multiple
      logistic regression. Fixed-facility and transportation-related events were
      analyzed separately. RESULTS: For fixed-facility events, 2,327 (8%) resulted in
      at least one victim and 2,844 (10%) involved ordered evacuations. For
      transportation-related events, 759 (8%) resulted in at least one victim, and 405
      (4%) caused evacuation orders. Fire and/or explosion were the strongest risk
      factors for events involving either victims or evacuations. Stratified analysis
      of fixed-facility events involving victims showed a strong association for acid
      releases in the agriculture, forestry, and fisheries industry. Chlorine releases
      in fixed-facility events resulted in victims and evacuations in more industry
      categories than any other substance. CONCLUSIONS: Outreach efforts should focus
      on preventing and preparing for fires and explosions, acid releases in the
      agricultural industry, and chlorine releases in fixed facilities.

PMID- 15496224
TI  - Nutrition and cancer: a review of the evidence for an anti-cancer diet.
AB  - It has been estimated that 30-40 percent of all cancers can be prevented by
      lifestyle and dietary measures alone. Obesity, nutrient sparse foods such as
      concentrated sugars and refined flour products that contribute to impaired
      glucose metabolism (which leads to diabetes), low fiber intake, consumption of
      red meat, and imbalance of omega 3 and omega 6 fats all contribute to excess
      cancer risk. Intake of flax seed, especially its lignan fraction, and abundant
      portions of fruits and vegetables will lower cancer risk. Allium and cruciferous
      vegetables are especially beneficial, with broccoli sprouts being the densest
      source of sulforophane. Protective elements in a cancer prevention diet include
      selenium, folic acid, vitamin B-12, vitamin D, chlorophyll, and antioxidants such
      as the carotenoids (alpha-carotene, beta-carotene, lycopene, lutein,
      cryptoxanthin). Ascorbic acid has limited benefits orally, but could be very
      beneficial intravenously. Supplementary use of oral digestive enzymes and
      probiotics also has merit as anticancer dietary measures. When a diet is compiled
      according to the guidelines here it is likely that there would be at least a 60
      70 percent decrease in breast, colorectal, and prostate cancers, and even a 40-50
      percent decrease in lung cancer, along with similar reductions in cancers at
      other sites. Such a diet would be conducive to preventing cancer and would favor
      recovery from cancer as well.

PMID- 15496227
TI  - Factors influencing quality of life in patients with active tuberculosis.
AB  - BACKGROUND: With effective treatment strategies, the focus of tuberculosis (TB)
      management has shifted from the prevention of mortality to the avoidance of
      morbidity. As such, there should be an increased focus on quality of life (QoL)
      experienced by individuals being treated for TB. The objective of our study was
      to identify areas of QoL that are affected by active TB using focus groups and
      individual interviews. METHODS: English, Cantonese, and Punjabi-speaking subjects
      with active TB who were receiving treatment were eligible for recruitment into
      the study. Gender-based focus group sessions were conducted for the inner city
      participants but individual interviews were conducted for those who came to the
      main TB clinic or were hospitalized. Facilitators used open-ended questions and
      participants were asked to discuss their experiences of being diagnosed with
      tuberculosis, what impact it had on their lives, issues around adherence to anti
      TB medications and information pertaining to their experience with side effects
      to these medications. All data were audio-recorded, transcribed verbatim, and
      analyzed using constant comparative analysis. RESULTS: 39 patients with active TB
      participated. The mean age was 46.2 years (SD 18.4) and 62% were male. Most were
      Canadian-born being either Caucasian or Aboriginal. Four themes emerged from the
      focus groups and interviews. The first describes issues related to the diagnosis
      of tuberculosis and sub-themes were identified as 'symptoms', 'health care
      provision', and 'emotional impact'. The second theme discusses TB medication
      factors and the sub-themes identified were 'adverse effects', 'ease of
      administration', and 'adherence'. The third theme describes social support and
      functioning issues for the individuals with TB. The fourth theme describes health
      behavior issues for the individuals with TB and the identified sub-themes were
      "behavior modification" and "TB knowledge." CONCLUSION: Despite the ability to
      cure TB, there remains a significant impact on QOL. Since much attention is spent
      on preventative or curative mechanisms, the impact of this condition on QoL is
      often not considered. Attention to the issues experienced by patients being
      treated for TB may optimize adherence and treatment success.

PMID- 15496228
TI  - Trends in suicide in Scotland 1981 - 1999: age, method and geography.
AB  - BACKGROUND: Male suicide rates continued to increase in Scotland when rates in
      England and Wales declined. Female rates decreased, but at a slower rate than in
      England and Wales. Previous work has suggested higher than average rates in some
      rural areas of Scotland. This paper describes trends in suicide and undetermined
      death in Scotland by age, gender, geographical area and method for 1981 - 1999.
      METHODS: Deaths from suicide and undetermined cause in Scotland from 1981 - 1999
      were identified using the records of the General Registrar Office. The deaths of
      people not resident in Scotland were excluded from the analysis. Death rates were
      calculated by area of residence, age group, gender, and method. Standardised
      Mortality Ratios (SMRs) and 95% confidence intervals were calculated for rates by
      geographical area. RESULTS: Male rates of death by suicide and undetermined death
      increased by 35% between 1981 - 1985 and 1996 - 1999. The largest increases were
      in the youngest age groups. All age female rates decreased by 7% in the same
      period, although there were increases in younger female age groups. The commonest
      methods of suicide in men were hanging, self-poisoning and car exhaust fumes.
      Hanging in males increased by 96.8% from 45 per million to 89 per million,
      compared to a 30.7% increase for self-poisoning deaths. In females, the commonest
      method of suicide was self-poisoning. Female hanging death rates increased in the
      time period. Male SMRs for 1981 - 1999 were significantly elevated in Western
      Isles (SMR 138, 95% CI 112 - 171), Highland (135, CI 125 - 147), and Greater
      Glasgow (120, CI 115 - 125). The female SMR was significantly high only in
      Greater Glasgow (120, CI 112 - 128). CONCLUSION: All age suicide rates increased
      in men and decreased in women in Scotland in 1981 - 1999. Previous findings of
      higher than expected male rates in some rural areas were supported. Rates were
      also high in Greater Glasgow, one of the most deprived areas of Scotland. There
      were changes in the methods used, with an increase in hanging deaths in men, and
      a smaller increase in hanging in women. Altered choice of method may have
      contributed to the increased male deaths.

PMID- 15496229
TI  - Phylogenetic inference in Rafflesiales: the influence of rate heterogeneity and
      horizontal gene transfer.
AB  - BACKGROUND: The phylogenetic relationships among the holoparasites of
      Rafflesiales have remained enigmatic for over a century. Recent molecular
      phylogenetic studies using the mitochondrial matR gene placed Rafflesia,
      Rhizanthes and Sapria (Rafflesiaceae s. str.) in the angiosperm order
      Malpighiales and Mitrastema (Mitrastemonaceae) in Ericales. These phylogenetic
      studies did not, however, sample two additional groups traditionally classified
      within Rafflesiales (Apodantheaceae and Cytinaceae). Here we provide molecular
      phylogenetic evidence using DNA sequence data from mitochondrial and nuclear
      genes for representatives of all genera in Rafflesiales. RESULTS: Our analyses
      indicate that the phylogenetic affinities of the large-flowered clade and
      Mitrastema, ascertained using mitochondrial matR, are congruent with results from
      nuclear SSU rDNA when these data are analyzed using maximum likelihood and
      Bayesian methods. The relationship of Cytinaceae to Malvales was recovered in all
      analyses. Relationships between Apodanthaceae and photosynthetic angiosperms
      varied depending upon the data partition: Malvales (3-gene), Cucurbitales (matR)
      or Fabales (atp1). The latter incongruencies suggest that horizontal gene
      transfer (HGT) may be affecting the mitochondrial gene topologies. The lack of
      association between Mitrastema and Ericales using atp1 is suggestive of HGT, but
      greater sampling within eudicots is needed to test this hypothesis further.
      CONCLUSIONS: Rafflesiales are not monophyletic but composed of three or four
      independent lineages (families): Rafflesiaceae, Mitrastemonaceae, Apodanthaceae
      and Cytinaceae. Long-branch attraction appears to be misleading parsimony
      analyses of nuclear small-subunit rDNA data, but model-based methods (maximum
      likelihood and Bayesian analyses) recover a topology that is congruent with the
      mitochondrial matR gene tree, thus providing compelling evidence for organismal
      relationships. Horizontal gene transfer appears to be influencing only some taxa
      and some mitochondrial genes, thus indicating that the process is acting at the
      single gene (not whole genome) level.

PMID- 15496230
TI  - Age-related changes in serum growth hormone, insulin-like growth factor-1 and
      somatostatin in system lupus erythematosus.
AB  - BACKGROUND: Systemic lupus erythematosus is an age- and gender-associated
      autoimmune disorder. Previous studies suggested that defects in the
      hypothalamic/pituitary axis contributed to systemic lupus erythematosus disease
      progression which could also involve growth hormone, insulin-like growth factor-1
      and somatostatin function. This study was designed to compare basal serum growth
      hormone, insulin-like growth factor-1 and somatostatin levels in female systemic
      lupus erythematosus patients to a group of normal female subjects. METHODS: Basal
      serum growth hormone, insulin-like growth factor-1 and somatostatin levels were
      measured by standard radioimmunoassay. RESULTS: Serum growth hormone levels
      failed to correlate with age (r2 = 3.03) in the entire group of normal subjects
      (i.e. 20 - 80 years). In contrast, serum insulin-like growth factor-1 levels were
      inversely correlated with age (adjusted r2 = 0.092). Of note, serum growth
      hormone was positively correlated with age (adjusted r2 = 0.269) in the 20 - 46
      year range which overlapped with the age range of patients in the systemic lupus
      erythematosus group. In that regard, serum growth hormone levels were not
      significantly higher compared to either the entire group of normal subjects (20 -
      80 yrs) or to normal subjects age-matched to the systemic lupus erythematosus
      patients. Serum insulin-like growth factor-1 levels were significantly elevated
      (p < 0.001) in systemic lupus erythematosus patients, but only when compared to
      the entire group of normal subjects. Serum somatostatin levels differed from
      normal subjects only in older (i.e. >55 yrs) systemic lupus erythematosus
      patients. CONCLUSIONS: These results indicated that systemic lupus erythematosus
      was not characterized by a modulation of the growth hormone/insulin-like growth
      factor-1 paracrine axis when serum samples from systemic lupus erythematosus
      patients were compared to age- matched normal female subjects. These results in
      systemic lupus erythematosus differ from those previously reported in other
      musculoskeletal disorders such as rheumatoid arthritis, osteoarthritis,
      fibromyalgia, diffuse idiopathic skeletal hyperostosis and hypermobility syndrome
      where significantly higher serum growth hormone levels were found. Somatostatin
      levels in elderly systemic lupus erythematosus patients may provide a clinical
      marker of disease activity in these patients.

PMID- 15496232
TI  - Early detection of Pseudomonas aeruginosa--comparison of conventional versus
      molecular (PCR) detection directly from adult patients with cystic fibrosis (CF).
AB  - BACKGROUND: Pseudomonas aeruginosa (PA) is the most important bacterial pathogen
      in patients with cystic fibrosis (CF) patients. Currently, routine
      bacteriological culture on selective/non- selective culture media is the
      cornerstone of microbiological detection. The aim of this study was to compare
      isolation rates of PA by conventional culture and molecular (PCR) detection
      directly from sputum. METHODS: Adult patients (n = 57) attending the regional
      adult CF centre in Northern Ireland, provided fresh sputum following airways
      clearance exercise. Following processing of the specimen with sputasol (1:1 vol),
      the specimen was examined for the presence of PA by plating onto a combination of
      culture media (Pseudomonas isolation agar, Blood agar & McConkey agar). In
      addition, from the same specimen, genomic bacterial DNA was extracted (1 ml) and
      was amplified employing two sequence-specific targets, namely (i) the outer
      membrane protein (oprL) gene locus and (ii) the exotoxin A (ETA) gene locus.
      RESULTS: By sputum culture, there were 30 patients positive for PA, whereas by
      molecular techniques, there were 35 positive patients. In 39 patients (22 PA +ve
      & 17 PA -ve), there was complete agreement between molecular and conventional
      detection and with both PCR gene loci. The oprL locus was more sensitive than the
      ETA locus, as the former was positive in 10 more patients and there were no
      patients where the ETA was positive and the oprL target negative. Where a PCR
      +ve/culture -ve result was recorded (10 patients), we followed these patients and
      recorded that 5 of these patients converted to being culture-positive at times
      ranging from 4-17 months later, with a mean lag time of 4.5 months. CONCLUSIONS:
      This study indicates that molecular detection of PA in sputum employing the oprL
      gene target, is a useful technique in the early detection of PA, gaining on
      average 4.5 months over conventional culture. It now remains to be established
      whether aggressive antibiotic intervention at this earlier stage, based on PCR
      detection, has any significant benefits on clinical outcome.

PMID- 15496231
TI  - Practice patterns of naturopathic physicians: results from a random survey of
      licensed practitioners in two US States.
AB  - BACKGROUND: Despite the growing use of complementary and alternative medicine
      (CAM) by consumers in the U.S., little is known about the practice of CAM
      providers. The objective of this study was to describe and compare the practice
      patterns of naturopathic physicians in Washington State and Connecticut. METHODS:
      Telephone interviews were conducted with state-wide random samples of licensed
      naturopathic physicians and data were collected on consecutive patient visits in
      1998 and 1999. The main outcome measures were: Sociodemographic, training and
      practice characteristics of naturopathic physicians; and demographics, reasons
      for visit, types of treatments, payment source and visit duration for patients.
      RESULT: One hundred and seventy practitioners were interviewed and 99 recorded
      data on a total of 1817 patient visits. Naturopathic physicians in Washington and
      Connecticut had similar demographic and practice characteristics. Both the
      practitioners and their patients were primarily White and female. Almost 75% of
      all naturopathic visits were for chronic complaints, most frequently fatigue,
      headache, and back symptoms. Complete blood counts, serum chemistries, lipids
      panels and stool analyses were ordered for 4% to 10% of visits. All other
      diagnostic tests were ordered less frequently. The most commonly prescribed
      naturopathic therapeutics were: botanical medicines (51% of visits in
      Connecticut, 43% in Washington), vitamins (41% and 43%), minerals (35% and 39%),
      homeopathy (29% and 19%) and allergy treatments (11% and 13%). The mean visit
      length was about 40 minutes. Approximately half the visits were paid directly by
      the patient. CONCLUSION: This study provides information that will help other
      health care providers, patients and policy makers better understand the nature of
      naturopathic care.

PMID- 15496233
TI  - Translation research: from accurate diagnosis to appropriate treatment.
AB  - This review article focuses on the various aspects of translational research,
      where research on human subjects can ultimately enhance the diagnosis and
      treatment of future patients. While we will use specific examples relating to the
      asbestos related cancer mesothelioma, it should be stressed that the general
      approach outlined throughout this review is readily applicable to other diseases
      with an underlying molecular basis. Through the integration of molecular-based
      technologies, systematic tissue procurement and medical informatics, we now have
      the ability to identify clinically applicable "genotype"-"phenotype" associations
      across cohorts of patients that can rapidly be translated into useful diagnostic
      and treatment strategies. This review will touch on the various steps in the
      translational pipeline, and highlight some of the most essential elements as well
      as possible roadblocks that can impact success of the program. Critical issues
      with regard to Institutional Review Board (IRB) and Health Insurance Portability
      and Accountability Act (HIPAA) compliance, data standardization, sample
      procurement, quality control (QC), quality assurance (QA), data analysis,
      preclinical models and clinical trials are addressed. The various facets of the
      translational pipeline have been incorporated into a fully integrated
      computational system, appropriately named Dx2Tx. This system readily allows for
      the identification of new diagnostic tests, the discovery of biomarkers and
      drugable targets, and prediction of optimal treatments based upon the underlying
      molecular basis of the disease.

PMID- 15496234
TI  - Genomic-scale analysis of bacterial gene and protein expression in the host.
AB  - The developing complementary technologies of DNA microarrays and proteomics are
      allowing the response of bacterial pathogens to different environments to be
      probed at the whole genome level. Although using these technologies to analyze
      pathogens within a host is still in its infancy, initial studies indicate that
      these technologies will be valuable tools for understanding how the pathogen
      reacts to the in vivo microenvironment. Some bacterial pathogens have been shown
      to substantially modify their surface components in response to the host immune
      system and modify their energy metabolism and transport pathways to allow
      efficient growth within the host. Further detailed analyses of these responses
      will increase understanding of the molecular mechanisms of pathogenesis, identify
      new bacterial virulence factors, and aid in the design of new vaccines.

PMID- 15496235
TI  - Vibrio vulnificus in Taiwan.
AB  - Residents in Taiwan are often exposed to marine microorganisms through seafood
      and occupational exposure. The number of reported cases of infection attributable
      to this organism has increased since the first case was reported in 1985. The
      increasing number of cases may be caused by greater disease activity or improved
      recognition by clinicians or laboratory workers. We analyze a clinical-case
      series of 84 patients with Vibrio vulnificus infection from 1995 to 2000 and
      describe the molecular epidemiologic features of pathogens isolated from these
      patients. The spectrum of clinical manifestations and outcomes, options of
      antimicrobial therapy, and virulence mechanisms were investigated. Results of
      molecular typing of isolates from humans and marine environment in this country
      had a high genetic divergence among these isolates. Education and measures are
      needed to prevent this emerging disease.

PMID- 15496236
TI  - West Nile virus in California.
AB  - West Nile virus (WNV) was first isolated in California during July 2003 from a
      pool of Culex tarsalis collected near El Centro, Imperial County. WNV
      transmission then increased and spread in Imperial and Coachella Valleys, where
      it was tracked by isolation from pools of Cx. tarsalis, seroconversions in
      sentinel chickens, and seroprevalence in free-ranging birds. WNV then dispersed
      to the city of Riverside, Riverside County, and to the Whittier Dam area of Los
      Angeles County, where it was detected in dead birds and pools of Cx. pipiens
      quinquefasciatus. By October, WNV was detected in dead birds collected from
      riparian corridors in Los Angeles, west to Long Beach, and through inland valleys
      south from Riverside to San Diego County. WNV was reported concurrently from
      Arizona in mid-August and from Baja, Mexico, in mid-November. Possible mechanisms
      for virus introduction, amplification, and dispersal are discussed.

PMID- 15496237
TI  - Crimean-Congo hemorrhagic fever in Turkey.
AB  - In 2002 and 2003, a total of 19 persons in Turkey had suspected cases of Crimean
      Congo hemorrhagic fever (CCHF) or a similar viral infection. Six serum samples
      were tested; all six were found positive for immunoglobulin M antibodies against
      CCHF virus. Two of the samples yielded CCHF virus isolates. Genetic analysis of
      the virus isolates showed them to be closely related to isolates from former
      Yugoslavia and southwestern Russia. These cases are the first of CCHF reported
      from Turkey. Eighteen patients handled livestock, and one was a nurse with
      probable nosocomial infection. The case-fatality rate was 20% among confirmed
      CCHF case-patients (1 of 5 patients), and the overall case-fatality rate was 11%
      (2 of 19 patients). In addition to previously reported symptoms and signs, we
      report hemophagocytosis in 50% of our patients, which is the first report of this
      clinical phenomenon associated with CCHF.

PMID- 15496238
TI  - Predicting antigenic variants of influenza A/H3N2 viruses.
AB  - Current inactivated influenza vaccines provide protection when vaccine antigens
      and circulating viruses share a high degree of similarity in hemagglutinin
      protein. Five antigenic sites in the hemagglutinin protein have been proposed,
      and 131 amino acid positions have been identified in the five antigenic sites. In
      addition, 20, 18, and 32 amino acid positions in the hemagglutinin protein have
      been identified as mouse monoclonal antibody-binding sites, positively selected
      codons, and substantially diverse codons, respectively. We investigated these
      amino acid positions for predicting antigenic variants of influenza A/H3N2
      viruses in ferrets. Results indicate that the model based on the number of amino
      acid changes in the five antigenic sites is best for predicting antigenic
      variants (agreement = 83%). The methods described in this study could be applied
      to predict vaccine-induced cross-reactive antibody responses in humans, which may
      further improve the selection of vaccine strains.

PMID- 15496239
TI  - Mycobacterium ulcerans disease (Buruli ulcer) in rural hospital, Southern Benin,
      1997-2001.
AB  - Data from 1,700 patients living in southern Benin were collected at the Centre
      Sanitaire et Nutritionnel Gbemoten, Zagnanado, Benin, from 1997 through 2001. In
      the Zou region in 1999, Buruli ulcer (BU) had a higher detection rate
      (21.5/100,000) than leprosy (13.4/100,000) and tuberculosis (20.0/100,000). More
      than 13% of the patients had osteomyelitis. Delay in seeking treatment declined
      from 4 months in 1989 to 1 month in 2001, and median hospitalization time
      decreased from 9 months in 1989 to 1 month in 2001. This reduction is attributed,
      in part, to implementing an international cooperation program, creating a
      national BU program, and making advances in patient care.

PMID- 15496240
TI  - SARS in three categories of hospital workers, Hong Kong.
AB  - We analyzed attack rates for severe acute respiratory syndrome (SARS) in three
      categories of hospital workers (nurses, nonmedical support staff, and other
      technical or medical staff) in all public hospitals in Hong Kong that had
      admitted SARS patients. Of 16 such hospitals, 14 had cases. The overall attack
      rate was 1.20%. Nonmedical support staff had the highest attack rate (2.73%). The
      odds ratios of group nonmedical support staff versus those of nurses and of
      nonmedical support staff versus other technical or medical staff were 2.30 (p <
      0.001) and 9.78 (p < 0.001), respectively. The number of affected staff and
      attack rates were significantly correlated with the number of SARS patients
      admitted (r = 0.914 and 0.686, respectively). Affected patients were concentrated
      in three hospitals and in the earlier phase of the epidemic. Cleaning and
      clerical staff on hospital wards were at a much higher risk.

PMID- 15496241
TI  - Long-term prognosis for clinical West Nile virus infection.
AB  - Relatively little is known about the long-term prognosis for patients with
      clinical West Nile virus (WNV) infection. We conducted a study to describe the
      recovery of New York City residents infected during the 1999 WNV encephalitis
      outbreak. Patients were interviewed by telephone on self-perceived health
      outcomes 6, 12, and 18 months after WNV illness onset. At 12 months, the
      prevalence of physical, functional, and cognitive symptoms was significantly
      higher than that at baseline, including muscle weakness, loss of concentration,
      confusion, and lightheadedness. Only 37% achieved a full recovery by 1 year.
      Younger age at infection was the only significant predictor of recovery. Efforts
      aimed at preventing WNV infection should focus on elderly populations who are at
      increased risk for neurologic manifestations and more likely to experience long
      term sequelae of WNV illness. More studies are needed to document the long-term
      sequelae of this increasingly common infection.

PMID- 15496242
TI  - Serotype III Streptococcus agalactiae from bovine milk and human neonatal
      infections.
AB  - Streptococcus agalactiae (group B streptococcus [GBS]) causes invasive human
      infections and bovine mastitis. This study examined the genetic relationship
      between bovine and human serotype III GBS by using molecular techniques that
      classify human serotype III GBS into four distinct phylogenetic lineages. Bovine
      serotype III GBS were largely contained in two lineages, which are distinct from
      the two major lineages (restriction digest types III-2 and III-3) that infect
      human neonates. One of the bovine lineages closely resembles the human III-1
      lineage, whose members occasionally cause human neonatal infections. The bovine
      strains in the other lineage characteristically have an initiation factor IF2
      gene (infB) H allele and multilocus sequence types that are not found in human
      GBS strains. Evidence suggests that this "H allele" lineage is related to the
      human III-3 lineage. These results support the assertion that human and bovine
      GBS are largely unrelated and provide further insight into the genetic relation
      between human and bovine GBS.

PMID- 15496243
TI  - Thrombocytopenia and acute renal failure in Puumala hantavirus infections.
AB  - Nephropathia epidemica, caused by Puumala virus (PUUV) infection, is a form of
      hemorrhagic fever with renal syndrome of variable severity. Early prognostic
      markers for the severity of renal failure have not been established. We evaluated
      clinical and laboratory parameters of 15 consecutive patients with acute PUUV
      infection, which is endemic in the Alb-Danube region, South Germany. Severe renal
      failure (serum creatinine >620 micromol/L) was observed in seven patients; four
      required hemodialysis treatment. Low platelet count (<60 x 109/L), but not
      leukocyte count, C-reactive protein, or other parameters obtained at the initial
      evaluation, was significantly associated with subsequent severe renal failure (p
      = 0.004). Maximum serum creatinine was preceded by platelet count nadirs by a
      median of 4 days. Thrombocytopenia <60 x 109/L appears predictive of a severe
      course of acute renal failure in nephropathia epidemica, with potential value for
      risk-adapted clinical disease management.

PMID- 15496244
TI  - Pharmacy data for tuberculosis surveillance and assessment of patient management.
AB  - Underreporting tuberculosis (TB) cases can compromise surveillance. We evaluated
      the contribution of pharmacy data in three different managed-care settings and
      geographic areas. Persons with more than two anti-TB medications were identified
      by using pharmacy databases. Active TB was confirmed by using state TB
      registries, medical record review, or questionnaires from prescribing physicians.
      We identified 207 active TB cases, including 13 (6%) missed by traditional
      surveillance. Pharmacy screening identified 80% of persons with TB who had
      received their medications through health plan-reimbursed sources, but missed
      those treated solely in public health clinics. The positive predictive value of
      receiving more than two anti-TB medications was 33%. Pharmacy data also provided
      useful information about physicians' management of TB and patients' adherence to
      prescribed therapy. Pharmacy data can help public health officials to find TB
      cases and assess their management in populations that receive care in the private
      sector.

PMID- 15496245
TI  - Antimicrobial drug use and methicillin-resistant Staphylococcus aureus, Aberdeen,
      1996-2000.
AB  - Similar to many hospitals worldwide, Aberdeen Royal Infirmary has had an outbreak
      of methicillin-resistant Staphylococcus aureus (MRSA). In this setting, the
      outbreak is attributable to two major clones. The relationships between
      antimicrobial use and MRSA prevalence were analyzed by time-series analysis. From
      June 1997 to December 2000, dynamic, temporal relationships were found between
      monthly %MRSA and previous %MRSA, macrolide use, third-generation cephalosporin
      use, and fluoroquinolone use. This study suggests that use of antimicrobial drugs
      to which the MRSA outbreak strains are resistant may be an important factor in
      perpetuating the outbreak. Moreover, this study confirmed the ecologic effect of
      antimicrobial drug use (i.e., current antimicrobial use) may have an effect on
      resistance in future patients. Although these results may not be generalized to
      other hospitals, they suggest new directions for control of MRSA, which has thus
      far proved difficult and expensive.

PMID- 15496246
TI  - Acute encephalitis hospitalizations, California, 1990-1999: unrecognized
      arboviral encephalitis?
AB  - Historically, Western equine encephalomyelitis and St. Louis encephalitis caused
      substantial human and equine illness and death in California. This study
      describes the epidemiology of encephalitis with data from 13,807 patients
      hospitalized in California with acute encephalitis from 1990 through 1999. The
      incidence of encephalitis hospitalizations decreased over this period. The
      greatest proportion of case-patients was hospitalized in the winter. Encephalitis
      of unspecified origin was the most common diagnosis, and arboviral encephalitis
      was the least common. Some California counties had concurrent increases in
      encephalitis rates and in detected arboviral activity in sentinel chickens and
      mosquito vectors. However, a diagnosis of arboviral encephalitis was made for few
      hospitalized patients in these counties during these periods. Although some
      arboviral encephalitis cases may have been undiagnosed, such cases probably did
      not occur frequently. Active hospital-based surveillance during periods of
      heightened sylvatic arboviral activity could increase detection of arboviral
      encephalitis.

PMID- 15496247
TI  - Human herpesviruses 6 and 7 and central nervous system infection in children.
AB  - The role and frequency of human herpesviruses (HHV)-6 and -7 in central nervous
      system (CNS) diseases of children are unclear. Cerebrospinal fluid samples from
      245 pediatric patients (median age 43 days), submitted for evaluations of
      possible sepsis or of neurologic symptoms, were tested for HHV-6 and HHV-7 DNA by
      polymerase chain reaction. HHV-6 DNA was found in 3 of 245 samples, and HHV-7 was
      found in 0 of 245 samples. The three patients with HHV-6 DNA were <2 months of
      age. HHV-6 was likely pathogenic in two patients with meningitis who lacked
      evidence of another microbiologic cause. HHV-6 and HHV-7 are uncommon causes of
      CNS infection in children. HHV-6 may occasionally cause meningitis in young
      infants.

PMID- 15496249
TI  - Print media response to SARS in New Zealand.
AB  - To examine the media response to severe acute respiratory syndrome, we reviewed
      New Zealand's major newspaper (261 articles for 3 months). While important
      accurate health messages were frequently included, some were missed (e.g., hand
      washing in only 2% of articles). No incorrect information was identified, and
      health spokespersons were accurately quoted.

PMID- 15496248
TI  - Group G streptococcal bacteremia in Jerusalem.
AB  - Group G Streptococcus (GGS) can cause severe infections, including bacteremia.
      These organisms often express a surface protein homologous to the Streptococcus
      pyogenes M protein. We retrospectively studied the characteristics of patients
      from the Hadassah Medical Center with GGS bacteremia from 1989 to 2000. Ninety
      four cases of GGS bacteremia were identified in 84 patients. The median age was
      62 years, 54% were males, and 92% had underlying diseases (35% had a malignancy,
      and 35% had diabetes mellitus). The most frequent source for bacteremia was
      cellulitis (61%). emm typing of 56 available isolates disclosed 13 different
      types, including 2 novel types. Six patients had recurrent bacteremia with two to
      four bacteremic episodes, five had chronic lymphatic disorders, and two had emm
      type stG840.0 in every episode. Recurrent bacteremia has not been described for
      invasive group A Streptococcus. We describe an entity of recurrent GGS
      bacteremia, which is associated with lymphatic disorders and possibly with emm
      stG840.0.

PMID- 15496250
TI  - Crimean-Congo hemorrhagic fever in Bulgaria.
AB  - We report the epidemiologic characteristics of Crimean-Congo hemorrhagic fever in
      Bulgaria, as well as the first genetic characterization of the virus strains
      circulating in the country in 2002 to 2003 that caused disease in humans.

PMID- 15496251
TI  - Recombinant human enterovirus 71 in hand, foot and mouth disease patients.
AB  - Hand, foot and mouth disease (HFMD) is a common illness of infants and young
      children <10 years of age. It is characterized by fever, ulcers in the oral
      cavity, and rashes with blisters that appear on the palm and sole. The most
      common causal agents of HFMD are coxsackievirus A16 (CV-A16) and human
      enterovirus 71 (HEV71), but other enteroviruses, including CV-A5 and CV-A10, can
      also cause it. When caused by CV-A16 infection, it is usually a mild disease, and
      patients normally recover without requiring any special medical attention.

PMID- 15496252
TI  - Syphilis in the HIV era.
AB  - The incidence of syphilis has consistently increased from 2000 to 2002. We report
      a case of acquired syphilis with symptoms of Tullio phenomenon in a patient
      concurrently diagnosed with HIV infection. The resurgence of syphilis in HIV
      positive groups at high risk has public health implications for prevention of
      both diseases.

PMID- 15496253
TI  - Swimming and Campylobacter infections.
AB  - A matched case-control study was conducted to study risk factors for domestically
      acquired sporadic Campylobacter infections in Finland. Swimming in natural
      sources of water was a novel risk factor. Eating undercooked meat and drinking
      dug-well water were also independent risk factors for Campylobacter infection.

PMID- 15496254
TI  - Spotted-fever group Rickettsia in Dermacentor variabilis, Maryland.
AB  - Three-hundred ninety-two adult Dermacentor variabilis were collected from six
      Maryland counties during the spring, summer, and fall of 2002. Infection
      prevalence for spotted fever group Rickettsia was 3.8%, as determined by
      polymerase chain reaction. Single strand conformational polymorphism (SSCP)
      analysis followed by sequencing indicated that all infections represented a
      single rickettsial taxon, Rickettsia montanensis.

PMID- 15496255
TI  - Human Escherichia coli O157:H7 genetic marker in isolates of bovine origin.
AB  - The antiterminator Q gene of bacteriophage 933W (Q933) was identified upstream of
      the stx2 gene in 90% of human disease-origin Escherichia coli O157:H7 isolates
      and in 44.5% of bovine isolates. Shiga toxin production was higher in Q933
      positive isolates than Q933-negative isolates. This genetic marker may provide a
      useful molecular tool for epidemiologic studies.

PMID- 15496256
TI  - SARS risk perception, knowledge, precautions, and information sources, the
      Netherlands.
AB  - Severe acute respiratory syndrome (SARS)-related risk perceptions, knowledge,
      precautionary actions, and information sources were studied in the Netherlands
      during the 2003 SARS outbreak. Although respondents were highly aware of the SARS
      outbreak, the outbreak did not result in unnecessary precautionary actions or
      fears.

PMID- 15496257
TI  - Flies and Campylobacter infection of broiler flocks.
AB  - A total of 8.2% of flies caught outside a broiler house in Denmark had the
      potential to transmit Campylobacter jejuni to chickens, and hundreds of flies per
      day passed through the ventilation system into the broiler house. Our study
      suggests that flies may be an important source of Campylobacter infection of
      broiler flocks in summer.

PMID- 15496258
TI  - Rickettsia parkeri in Amblyomma triste from Uruguay.
AB  - Our goal was to detect whether spotted fever group Rickettsia are found in the
      suspected vector of rickettsioses, Amblyomma triste, in Uruguay. Rickettsia
      parkeri was detected in A. triste, which suggests that this species could be
      considered a pathogenic agent responsible for human rickettsioses in Uruguay.

PMID- 15496260
TI  - Protective behavior survey, West Nile virus, British Columbia.
AB  - We investigated personal protective behaviors against West Nile virus infection.
      Barriers to adopting these behaviors were identified, including the perception
      that DEET (N,N-diethyl-m-toluamide and related compounds) is a health and
      environmental hazard. Televised public health messages and knowing that family or
      friends practiced protective behaviors were important cues to action.

PMID- 15496259
TI  - Hantavirus infection in Anajatuba, Maranhao, Brazil.
AB  - In 2000, the first outbreak of hantavirus pulmonary syndrome was recognized in
      the Brazilian Amazon (Maranhao State). An epidemiologic study identified a 13.3%
      prevalence of hantavirus-specific immunoglobulin G. The analysis of risk factors
      suggests that persons are occupationally exposed to infected rodents in the crop
      fields.

PMID- 15496261
TI  - Current Treatment Options for Patients with Endocarditis: The Evolving
      Indications for Cardiac Surgery.
AB  - Infective endocarditis (IE) is a serious and deadly disease. Despite medical
      advances over the past half century, more than one half of patients with IE
      suffer a serious complication, and the mortality rate remains approximately 20%
      during the initial hospitalization and approaches 40% at 1 year. In patients with
      documented IE, the treatment centers on two main aspects: effective antibiotic
      therapy and consideration of surgical therapy. Effective antibiotic therapy is
      the mainstay of treatment and focuses on sustained bactericidal concentrations
      tailored specifically to the causative microorganism. Surgical therapy is also an
      important option for many patients with IE. The goals of surgical therapy are to
      eradicate the focus of infection, to repair endocardial destruction, and to
      prevent the development of complications and relapse of infection. Ideally,
      surgical therapy should offer a survival advantage over medical therapy alone.
      Recent evidence supports the survival benefit of surgery in patients with IE,
      specifically in those with heart failure and complicated, left-sided IE. Future
      therapeutic strategies may include broader indications for surgery, as well as
      new treatments such as immune-modulating agents.

PMID- 15496262
TI  - Pulmonary Arterial Hypertension: New Management Options.
AB  - The past decade has realized remarkable advances in the treatment of pulmonary
      arterial hypertension (PAH), a progressive and potentially fatal disease. A small
      proportion of patients will have a dramatic hemodynamic response to acute
      vasodilator testing performed at the time of right heart catheterization and may
      be candidates for calcium channel blocker therapy. The vast majority of patients
      with PAH will not benefit from calcium channel blockers and should be treated
      with one of the three US Food and Drug Administration-approved therapies for PAH;
      bosentan, treprostinil, or epoprostenol. Because of the ease of administration
      relative to other therapies, the majority of patients with functional class III
      symptoms should be treated with the oral nonselective endothelin antagonist
      bosentan. Randomized controlled trials with treprostinil have demonstrated
      improvements in exercise endurance and hemodynamics. Patients who are critically
      ill, with functional class IV symptoms, should be started on epoprostenol because
      it is the most rapidly effective therapy. Intravenous epoprostenol improves
      exercise endurance, quality of life, hemodynamics, and survival in PAH.
      Investigational therapies on the horizon include phosphodiesterase inhibitors,
      prostacyclin analogues with alternative delivery routes (eg, inhaled, oral), and
      selective endothelin A receptor antagonists. The future of PAH therapy will
      likely include combinations of these therapies based on the multiple mechanisms
      of action.

PMID- 15496263
TI  - Management of the Patient After Heart Transplant.
AB  - Cardiac transplantation is a highly effective therapy for selected patients with
      end-stage cardiac disease. The management of the patient after heart transplant
      involves three main strategies: optimization of immunosuppressive therapy,
      prevention of complications resulting from the transplant or the
      immunosuppressive agents, and treatment of those complications when they arise.
      For most patients, optimal current immunosuppression in the first year after
      transplantation consists of combination therapy with a calcineurin inhibitor (eg,
      cyclosporine or tacrolimus), corticosteroids, and an antimetabolite agent (eg,
      azathioprine or mycophenolate mofetil). Ideally, the corticosteroid is weaned and
      discontinued 1 to 2 years following transplantation and the patient is managed
      chronically with a two-drug immunosuppressive regimen. The major complications
      that occur following cardiac transplantation include infection, hypertension,
      diabetes, dyslipidemia, osteoporosis, graft coronary disease, renal
      insufficiency, and malignancy. Preventive efforts focused on infection,
      osteoporosis, renal insufficiency, and malignancy include minimization of
      immunosuppression. Once established, treatment of any of the above conditions
      generally relies on standard pharmacologic therapies; however, an understanding
      of potential drug interactions is critical. In addition, although standard
      nonpharmacologic therapies may be used to treat several of these conditions, one
      must be cognizant of special issues related to the post-transplant state.

PMID- 15496264
TI  - Left Ventricular Assist Devices as Destination Therapy for End-stage Heart
      Failure.
AB  - In the therapy of advanced heart failure, left ventricular assist devices
      represent an exciting new option. The role of mechanical circulatory support is
      currently limited predominantly by factors related to device durability. The
      population for whom mechanical circulatory support can be considered as permanent
      therapy is defined by those for whom improvement in survival and clinical
      function is expected from current devices. Reported device survival in the range
      of 50% at 1 year limits the present candidate population to those with greater
      than 50% mortality at 1 year, who are not eligible for cardiac transplantation,
      after which survival is 50% at 10 years. Even as we learn to identify these
      patients who are "sick enough" to warrant device placement and yet "well enough"
      to survive surgery, the devices and surgical techniques are evolving so that the
      outcomes are improving and the candidate population is expanding.

PMID- 15496265
TI  - Peripartum Cardiomyopathy: Current Therapeutic Perspectives.
AB  - Peripartum cardiomyopathy is a rare condition of unclear etiology that accounts
      for an important percentage of pregnancy-related deaths. Deaths from peripartum
      cardiomyopathy can be attributed to profound left ventricular failure,
      thromboembolic events, or arrhythmia. Prompt recognition of the condition,
      initiation of appropriate medical management, collaboration with perinatology for
      delivery management, referral to cardiac transplant centers when necessary, and
      counseling regarding future pregnancies is required for a successful outcome.
      Patients should be diagnosed by clinical evaluation and echocardiography. After
      establishing left ventricular dysfunction, a standard heart failure medical
      regimen should be instituted. Hospitalization should be considered for patients
      with class III or greater symptoms, or for those patients not responding to
      outpatient management. If the diagnosis is made in the antepartum period,
      delivery should be strongly considered. Endomyocardial biopsy has low yield in
      this situation and should not be considered standard care, especially because
      controversy exists over the effectiveness of immunosuppressive therapy for
      myocarditis. Selenium, pentoxifylline, and immune globulin have all been shown to
      have a beneficial effect in small series of patients. The addition of these
      agents to standard therapy, however, should be considered on a case-by-case
      basis. Anticoagulation should be considered in patients with ejection fractions
      less than 35%. Transplantation results in survival comparable to women with
      idiopathic-dilated cardiomyopathy, and should be pursued in the appropriate
      setting. Future pregnancies should be discouraged, even if the left ventricular
      function recovers. Significant improvement in ventricular function can be
      expected in up to 50% of patients.

PMID- 15496266
TI  - Approach to Hypertrophic Cardiomyopathy.
AB  - Hypertrophic cardiomyopathy is a genetic disease characterized by marked left
      ventricular (LV) hypertrophy. A dynamic LV outflow obstruction is present in
      approximately 20% of patients. Many affected individuals remain asymptomatic
      throughout life, others develop heart failure symptoms or atrial fibrillation
      (AF), and some die suddenly, often young and in the absence of previous symptoms.
      Stratification of sudden death risk is based on several markers, including a
      previous cardiac arrest, sustained ventricular tachycardia, family history of
      sudden death, extreme LV hypertrophy (>/= 30 mm), syncope, nonsustained
      ventricular tachycardia on Holter, and abnormal exercise blood pressure response.
      The implantable cardioverter-defibrillator is the most effective treatment for
      sudden death prevention, and should be considered in patients with either one
      strong or multiple risk factors. Important symptoms of heart failure develop in a
      minority of patients, largely as a consequence of diastolic dysfunction, and are
      usually treated with beta blockers, or verapamil. In patients with LV obstruction
      and severe symptoms unresponsive to medications, myectomy operation or alcohol
      septal ablation is indicated for relieving the gradient and improving quality of
      life. AF develops in approximately 20% of patients. Amiodarone is the most
      effective medication for preventing AF recurrences. In chronic AF, beta blockers
      or verapamil are usually effective for heart rate control. The threshold for
      anticoagulants is low, because even brief AF episodes have a substantial
      embolization risk.

PMID- 15496267
TI  - Neurohormonal Therapy for Congestive Heart Failure.
AB  - Guidelines for heart failure management have been published by the American
      College of Cardiology and the American Heart Association in 2001. These
      guidelines recommend the use of angiotensin-converting enzyme inhibitors and beta
      blockers to improve the symptoms and prognosis of heart failure. Despite being
      advocated as the cornerstone of medical management, these agents remain
      underutilized. Not only are these drugs underutilized, but titration to dosages
      with proven beneficial effects is lacking. Simply achieving widespread usage of
      these agents would have a significant impact on heart failure outcomes.

PMID- 15496268
TI  - Mitral Regurgitation: Current Treatment Options and Their Selection.
AB  - Mitral regurgitation (MR) is a mechanically complex hemodynamic abnormality of
      various etiologies that, if untreated, leads to myocardial dysfunction, heart
      failure, and sudden death. Unless hemodynamically severe, MR is not a major risk
      factor for debility and death. However, even more modest MR may impact on
      longevity and may create risk for thromboembolic and infectious sequelae.
      Currently, therapy for severe MR is surgical valve replacement or repair. When MR
      is not secondary to ischemic sequelae, generally accepted indications for surgery
      include any symptoms, left ventricular or right ventricular dysfunction or left
      ventricular geometric variations that reach defined levels of prognostic concern,
      or development of atrial fibrillation. However, low perioperative risk of repair
      causes some to urge surgery for severe MR irrespective of other findings. Similar
      controversy confounds decisions about mitral valve surgery during coronary artery
      bypass grafting when MR is a sequel of ischemic disease. Drug treatment has not
      altered MR outcome, although drugs can mitigate symptoms if surgery is
      contraindicated by intercurrent disease. There is no basis for prophylactic drug
      treatment to preserve myocardial function in asymptomatic patients.

PMID- 15496270
TI  - The dark side?

PMID- 15496271
TI  - ECOG 4402: randomized phase III-trial comparing two different rituximab dosing
      regimens for patients with low tumor burden indolent non-Hodgkin's lymphoma.

PMID- 15496269
TI  - Treatment of Arrhythmias in Patients with Congestive Heart Failure.
AB  - Both ventricular and atrial arrhythmias are commonly encountered in patients with
      ventricular dysfunction. In fact, roughly half of the deaths occurring in
      patients with ventricular dysfunction are caused by ventricular arrhythmias.
      Atrial arrhythmias in this patient population compromise left ventricular filling
      and if uncontrolled can exacerbate (and in some cases cause) the underlying
      myopathic process. Consequently, the diagnosis and treatment of these complex,
      and often life-threatening, arrhythmias is a critical component in the management
      of congestive heart failure (CHF). As the complexity of pharmacologic and
      nonpharmacologic antiarrhythmic therapy evolves, it has become increasingly
      important to understand the potential benefits and limitations of the various
      treatment modalities in the setting of patients with CHF. The management of
      arrhythmias in patients with CHF includes conventional drug therapies, as well as
      therapies directed specifically at treating the arrhythmias that are encountered.
      The treatment of atrial arrhythmias may include anticoagulation, drugs for rate
      control, rhythm control, or radiofrequency ablation. The treatment of ventricular
      arrhythmias, conversely, uses the implantable cardioverter-defibrillator to
      prevent sudden death, with adjuvant drug therapy or ablation for refractory
      ventricular tachycardia. This article provides an overview of the current state
      of-the-art arrhythmia management in patients with CHF.

PMID- 15496272
TI  - Erythropoietic agents in chemotherapy-induced anemia: a review of recent
      therapeutic progress, issues, and concerns.
AB  - Erythropoietic agents are widely used to alleviate anemia in patients with cancer
      receiving chemotherapy. Over the past decade, the efficacy and safety of these
      agents in improving hemoglobin levels and reducing transfusion requirements in an
      oncology setting has been demonstrated in a number of clinical trials. The
      overall risk-benefit relationship of treatment with erythropoietic agents is
      favorable, and these agents represent a tremendous advance in anemia management.
      This review discusses prevalent issues and addresses key questions concerning the
      use of erythropoietic agents for the treatment of chemotherapy-induced anemia.

PMID- 15496273
TI  - Cytokines and stem cell mobilization for autologous and allogeneic
      transplantation.
AB  - Mobilized peripheral blood has become the preferred source of stem cells for both
      autologous and allogeneic transplantation, and granulocyte colony-stimulating
      factor is the most widely used cytokine for mobilization. However, the mechanisms
      of cytokine-induced peripheral blood stem cell mobilization are not completely
      understood. Several recent studies suggest a model in which proteases released
      into the bone-marrow microenvironment during cytokine treatment play a critical
      role in mobilization. However, the finding that progenitor mobilization is normal
      in certain protease-deficient mice suggests that this model may be too
      simplistic. Here we review recent studies that advance our understanding of the
      biology of stem cell mobilization. We then discuss cytokines in current use and
      in development for mobilization of autologous and allogeneic peripheral blood
      stem cells.

PMID- 15496274
TI  - Growth factor priming in therapy of acute myelogenous leukemia.
AB  - Treatment of acute myelogenous leukemia (AML) incorporates the use of growth
      factors towards several objectives, including abbreviating the time of
      neutropenia, reducing susceptibility to infections, reducing length of
      hospitalization, and increasing susceptibility of the blasts to chemotherapy
      drugs, or priming. Priming is defined as the driving of leukemia cells into cell
      cycle in order to increase response to S-phase-specific drugs such as cytarabine
      (Ara-C). Growth factors that have been used in priming include both filgrastim (G
      CSF) and sagramostim (GM-CSF). Priming has often been applied in the treatment of
      older patients, who do not respond as well to standard treatment regimens, and
      whose disease was transformed from a myelodysplastic syndrome (MDS), or
      preleukemia. Recent, large randomized trials have demonstrated that although
      subgroups of patients may benefit, there does not appear to be any improvement in
      the complete remission rate sustained by inclusion of growth factor priming as
      part of the initial therapy of acute myelogenous leukemia.

PMID- 15496275
TI  - Pegfilgrastim use during chemotherapy: current and future applications.
AB  - Chemotherapy-induced myelosuppression is the most common dose-limiting side
      effect of cancer chemotherapy. Neutropenia is a serious risk with chemotherapy,
      associated with infectious complications, use of intravenous antibiotics,
      hospitalization, and even death. The occurrence of febrile neutropenia can lead
      to dose reductions and delay in subsequent cycles of chemotherapy that may have a
      detrimental affect on overall survival and disease-free survival. Granulocyte
      colony-stimulating factors (G-CSF) can reduce the duration of severe neutropenia,
      the incidence of febrile neutropenia, and allow planned dosing and timing of
      chemotherapy. Filgrastim is a G-CSF that has demonstrated benefit for the
      treatment and prophylaxis of chemotherapy-induced neutropenia (CIN), but its
      short half-life requires repeated daily subcutaneous injection. Pegfilgrastim is
      a recombinant G-CSF created by attaching a polyethylene glycol (PEG) molecule to
      the filgrastim protein. Once-per-cycle dosing of pegfilgrastim has been evaluated
      in clinical trials using myelosuppressive chemotherapy in breast cancer,
      Hodgkin's lymphoma, and non-Hodgkin's lymphoma. Trials have demonstrated that
      pegfilgrastim is comparable in safety and efficacy to filgrastim for decreasing
      the duration of severe neutropenia after chemotherapy in patients with nonmyeloid
      malignancy. This review will summarize recent clinical trial results and novel
      uses of pegfilgrastim.

PMID- 15496276
TI  - Granulocyte-macrophage-colony-stimulating factor and other cytokines: as adjuncts
      to cancer immunotherapy, stem cell transplantation, and vaccines.
AB  - A new role for myeloid-acting cytokines in regulating immune responses has been
      proposed based upon their activity on dendritic cell (DC) maturation and
      activation. Subsets of DCs may augment or inhibit cellular immune responses.
      Enhanced DC1 activity has been associated with enhanced cytotoxic immune
      responses. Granulocyte-macrophage-colony-stimulating factor (GM-CSF) and
      granulocyte-colony- stimulating factor (G-CSF) differ by their effects on
      enhancing the numbers or activity of DC1 or DC2 subsets of DCs, respectively. The
      increase in DC1 content and activity following local and systemic GM-CSF
      administration support a role for GM-CSF as an immune stimulant and vaccine
      adjuvant in cancer patients. The clinical activity of GM-CSF in anti-tumor immune
      responses has been documented in its use in tumor cell and DC vaccines, but a
      significant anti-tumor effect of parenterally administered GM-CSF in a randomized
      clinical study has yet to be consistently demonstrated. The successful use of
      myeloid acting cytokines to enhance anti-tumor responses will likely require
      targeting these drugs or activating DCs directly into the tumor microenvironment.

PMID- 15496277
TI  - Leukocyte reduction reduces the rate of febrile nonhemolytic transfusion
      reactions to platelets and red blood cells.

PMID- 15496278
TI  - Whole-blood donation: blood donor suitability and adverse events.
AB  - Approximately 3% to 3.5% of the US population donates whole blood each year.
      Physicians might be approached by a blood donor because of a donor suitability
      issue, a positive postdonation test, or a donation-related complication.
      Approximately 83% of blood donors successfully donate; but 13% are rejected
      because of a donor suitability issue; 1% have a positive test, which is often
      nonspecific or false-positive; and 2% to 4% of the phlebotomies are not
      successful. The most common adverse physical events based on donor interviews are
      bruise (23%), sore arm (10%), fatigue (8%), and vasovagal reaction (7%), while
      uncommon events include nerve irritation (0.9%), syncope (0.1-0.3%), and arterial
      puncture (0.01%). One in 3400 donors (0.033%) report seeking outside medical
      care. Serious injuries occur but are very rare. More often, blood donors do well
      and feel satisfied with the blood donation experience.

PMID- 15496279
TI  - Transfusion support in liver transplantation.
AB  - As liver transplantation becomes increasingly common and complex, the demands on
      the transfusion service grow. Liver transplant recipients present unique
      challenges not only in terms of blood supply, but requirements for specialized
      blood components, serologic problems, and immunologic effects of transfusion on
      both the allograft and the recipient. As a result of immunosuppression, liver
      transplant recipients are more susceptible to some transfusion complications such
      as cytomegalovirus (CMV) infection but not to transfusion associated graft versus
      host disease. The transfusion specialist must recommend the optimal approach to
      reducing the risk of these complications in liver transplant recipients.

PMID- 15496280
TI  - Bacterial contamination of blood products.
AB  - The occurrence of a septic reaction resulting from bacterial contamination of
      blood products, particularly with room-temperature stored platelets, is the most
      common transfusion-associated infectious risk in the United States. Bacterial
      contamination of blood products was first identified more than 60 years ago; yet,
      strategies to resolve this problem have proved daunting despite ongoing awareness
      and increasing concern especially in the last few years. With the recent US Food
      and Drug Administration (FDA) approval of culture methods for quality control
      testing of platelet units and the promulgation of accreditation standards by the
      College of American Pathologists and American Association of Blood Banks to
      detect bacterially contaminated platelet units and to prevent transfusion of
      these units, blood banks and transfusion services have finally started to address
      this problem, in a more standardized manner. Furthermore, as new methods of
      interdicting, inactivating and detecting bacterially contaminated blood products
      emerge, it is hoped that the problem of bacterial contamination of blood products
      will be overcome.

PMID- 15496281
TI  - Leukocyte antibodies and biologically active mediators in the pathogenesis of
      transfusion-related acute lung injury.
AB  - Transfusion-related acute lung injury (TRALI) is a clinical constellation of
      signs and symptoms associated with transfusion. In severe cases, the most
      prominent feature is acute onset of pulmonary edema. Two mechanisms have been
      advanced to explain pulmonary injury in this syndrome. One mechanism involves the
      presence of antibodies to white blood cells, usually in a transfused blood
      component. Interaction of antibodies, with white blood cells in the transfusion
      recipient, is hypothesized to cause cellular activation with release of cytokines
      resulting in pulmonary vascular endothelial damage and exudation of fluid across
      the pulmonary basement membrane. In the biologically active mediator mechanism,
      two events are hypothesized to cause TRALI. In the first event, polymorphonuclear
      cells become primed and pulmonary vascular endothelium becomes activated
      secondary to the production of biologically active mediators, as a result of
      physiologic stress. The second event is the infusion of biologically active
      mediators in a stored cellular blood product. The second event causes release of
      cellular activators with subsequent endothelial damage and exudation of fluid
      into the pulmonary alveoli.

PMID- 15496282
TI  - Proteomics in platelet science.
AB  - Proteomics, the rapid large-scale analysis of cellular proteins, is becoming an
      important tool in the study of human platelet biology. A number of investigators
      have used proteomics techniques to study platelets including two-dimensional gel
      electrophoresis, protein separation, and mass spectrometry protein
      identification. Most efforts have focused on: 1) cataloging the spectrum of
      proteins that comprise the normal platelet "proteome", 2) characterizing proteins
      released from activated platelets, and 3) identifying phosphoproteins generated
      upon platelet stimulation. The incorporation of modern proteomics technology to
      platelet studies will further our understanding of platelet activation, adhesion,
      and aggregation at the protein level. Moreover, proteomics offers hope that novel
      biomarkers can be discovered that diagnose inherited and/or acquired platelet
      disorders, or predict the susceptibility of such individuals to bleeding or
      thrombosis. Finally, proteomics could lead to identification of novel agents that
      have therapeutic value. This review discusses the current status and future
      opportunities of proteomics technologies in platelet science.

PMID- 15496283
TI  - Joint tests for quantitative trait loci in experimental crosses.
AB  - Selective genotyping is common because it can increase the expected correlation
      between QTL genotype and phenotype and thus increase the statistical power of
      linkage tests (i.e., regression-based tests). Linkage can also be tested by
      assessing whether the marginal genotypic distribution conforms to its
      expectation, a marginal-based test. We developed a class of joint tests that, by
      constraining intercepts in regression-based analyses, capitalize on the
      information available in both regression-based and marginal-based tests. We
      simulated data corresponding to the null hypothesis of no QTL effect and the
      alternative of some QTL effect at the locus for a backcross and an F2 intercross
      between inbred strains. Regression-based and marginal-based tests were compared
      to corresponding joint tests. We studied the effects of random sampling,
      selective sampling from a single tail of the phenotypic distribution, and
      selective sampling from both tails of the phenotypic distribution. Joint tests
      were nearly as powerful as all competing alternatives for random sampling and two
      tailed selection under both backcross and F2 intercross situations. Joint tests
      were generally more powerful for one-tailed selection under both backcross and F2
      intercross situations. However, joint tests cannot be recommended for one-tailed
      selective genotyping if segregation distortion is suspected.

PMID- 15496284
TI  - Identification of gametes and treatment of linear dependencies in the gametic QTL
      relationship matrix and its inverse.
AB  - The estimation of gametic effects via marker-assisted BLUP requires the inverse
      of the conditional gametic relationship matrix G. Both gametes of each animal can
      either be identified (distinguished) by markers or by parental origin. By
      example, it was shown that the conditional gametic relationship matrix is not
      unique but depends on the mode of gamete identification. The sum of both gametic
      effects of each animal--and therefore its estimated breeding value--remains
      however unaffected. A previously known algorithm for setting up the inverse of G
      was generalized in order to eliminate the dependencies between columns and rows
      of G. In the presence of dependencies the rank of G also depends on the mode of
      gamete identification. A unique transformation of estimates of QTL genotypic
      effects into QTL gametic effects was proven to be impossible. The properties of
      both modes of gamete identification in the fields of application are discussed.

PMID- 15496285
TI  - Enhanced individual selection for selecting fast growing fish: the "PROSPER"
      method, with application on brown trout (Salmo trutta fario).
AB  - Growth rate is the main breeding goal of fish breeders, but individual selection
      has often shown poor responses in fish species. The PROSPER method was developed
      to overcome possible factors that may contribute to this low success, using (1) a
      variable base population and high number of breeders (Ne >100), (2) selection
      within groups with low non-genetic effects and (3) repeated growth challenges.
      Using calculations, we show that individual selection within groups, with
      appropriate management of maternal effects, can be superior to mass selection as
      soon as the maternal effect ratio exceeds 0.15, when heritability is 0.25.
      Practically, brown trout were selected on length at the age of one year with the
      PROSPER method. The genetic gain was evaluated against an unselected control
      line. After four generations, the mean response per generation in length at one
      year was 6.2% of the control mean, while the mean correlated response in weight
      was 21.5% of the control mean per generation. At the 4th generation, selected
      fish also appeared to be leaner than control fish when compared at the same size,
      and the response on weight was maximal (approximately 130% of the control mean)
      between 386 and 470 days post fertilisation. This high response is promising,
      however, the key points of the method have to be investigated in more detail.

PMID- 15496287
TI  - Genetic diversity, introgression and relationships among West/Central African
      cattle breeds.
AB  - Genetic diversity, introgression and relationships were studied in 521
      individuals from 9 African Bos indicus and 3 Bos taurus cattle breeds in Cameroon
      and Nigeria using genotype information on 28 markers (16 microsatellite, 7 milk
      protein and 5 blood protein markers). The genotypes of 13 of the 16
      microsatellite markers studied on three European (German Angus, German Simmental
      and German Yellow) and two Indian (Nelore and Ongole) breeds were used to assess
      the relationships between them and the African breeds. Diversity levels at
      microsatellite loci were higher in the zebu than in the taurine breeds and were
      generally similar for protein loci in the breeds in each group. Microsatellite
      allelic distribution displayed groups of alleles specific to the Indian zebu,
      African taurine and European taurine. The level of the Indian zebu genetic
      admixture proportions in the African zebus was higher than the African taurine
      and European taurine admixture proportions, and ranged from 58.1% to 74.0%. The
      African taurine breed, Muturu was free of Indian zebu genes while its counter
      Namchi was highly introgressed (30.2%). Phylogenic reconstruction and principal
      component analysis indicate close relationships among the zebu breeds in Cameroon
      and Nigeria and a large genetic divergence between the main cattle groups-
      African taurine, European taurine and Indian zebu, and a central position for the
      African zebus. The study presents the first comprehensive information on the
      hybrid composition of the individual cattle breeds of Cameroon and Nigeria and
      the genetic relationships existing among them and other breeds outside of Africa.
      Strong evidence supporting separate domestication events for the Bos species is
      also provided.

PMID- 15496286
TI  - Mitochondrial D-loop sequence variation among Italian horse breeds.
AB  - The genetic variability of the mitochondrial D-loop DNA sequence in seven horse
      breeds bred in Italy (Giara, Haflinger, Italian trotter, Lipizzan, Maremmano,
      Thoroughbred and Sarcidano) was analysed. Five unrelated horses were chosen in
      each breed and twenty-two haplotypes were identified. The sequences obtained were
      aligned and compared with a reference sequence and with 27 mtDNA D-loop sequences
      selected in the GenBank database, representing Spanish, Portuguese, North
      African, wild horses and an Equus asinus sequence as the outgroup. Kimura two
      parameter distances were calculated and a cluster analysis using the Neighbour
      joining method was performed to obtain phylogenetic trees among breeds bred in
      Italy and among Italian and foreign breeds. The cluster analysis indicates that
      all the breeds but Giara are divided in the two trees, and no clear relationships
      were revealed between Italian populations and the other breeds. These results
      could be interpreted as showing the mixed origin of breeds bred in Italy and
      probably indicate the presence of many ancient maternal lineages with high
      diversity in mtDNA sequences.

PMID- 15496288
TI  - Apoptosis induced by 5-(N,N-hexamethylene)-amiloride in regenerating liver after
      partial hepatectomy.
AB  - The effects of a specific inhibitor of the Na+/H+ exchanger, 5-(N,N
      hexamethylene)-amiloride (HMA), on liver regeneration after partial hepatectomy
      were investigated. A single injection of HMA inhibited DNA synthesis and caused
      apoptosis in regenerating liver. Characteristic DNA fragmentation was observed at
      4 h after partial hepatectomy with HMA-injection. The activity of Jun N-terminal
      kinase (JNK) increased to a maximal level at 15 min after partial hepatectomy in
      HMA-injected rats, while it was not detected until 30 min in the control. Western
      blot analysis revealed that the injection of HMA markedly increased c-Jun and
      phosphorylated c-Jun protein levels at 30 min after partial hepatectomy. An
      increase in p53 was also observed at 30 min after the HMA-injection and was
      followed by the upregulation of p21WAF1/CIP1 protein expression at 1 h after
      partial hepatectomy. These results suggested that HMA induced apoptosis
      accompanied by the activation of JNK and the upregulation of c-Jun, p53 and
      p21WAF1/CIP1 expression at an early stage of liver regeneration.

PMID- 15496289
TI  - Chronic regulation of the expression of gap junction proteins connexin40,
      connexin43, and connexin45 in neonatal rat cardiomyocytes.
AB  - Gap junction channels form the basis of intercellular communication in the heart.
      In the working myocardium, the connexin43 (Cx43) is most abundantly found,
      whereas connexin40 (Cx40) is expressed in the atria and in the conduction system
      [together with low levels of connexin45 (Cx45)]. However, little is known about
      the differential regulation of the connexins by pathophysiologically stimuli such
      as tumor necrosis factor alpha (TNFalpha). Inasmuch as TNFalpha may play a
      contributory role in the concert of factors involved in the pathophysiology of
      heart failure and because this cardiac disease often leads to ventricular
      reentrant arrhythmia, the goal of our study was to find out whether TNFalpha may
      influence the expression of the cardiac connexins connexin43, connexin40, and
      connexin45. Neonatal rat cardiomyocytes were exposed to TNFalpha (10, 40, 100,
      400, and 1000 pg/ml) for 24 h with or without additional treatment with the
      mitogenic-activated protein kinase (MAP-kinase) inhibitors SB203580 [4-(4
      fluorophenyl)-2-(4-methyl-sulfinylphenyl)-5-(4-pyridyl)-1H-imidazole; 10(-5) M,
      protein38 mitogenic-activated protein kinase (p38 MAP kinase) inhibitor] or the
      MEK1 (mitogenic-activated protein kinase/extracellular signal-regulated kinase
      kinase) inhibitor PD98059 [2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; 10(
      5) M]. Connexin43, connexin40, and connexin45 expressions were analysed using
      Western blot analysis, immunohistology, and polymerase chain reaction (PCR)
      studies (connexin43 and connexin40). TNFalpha induced a concentration-dependent
      increase in connexin43 (by 2.9+/-0.6, P<0.05, n=5) but not in connexin40 or
      connexin45 expressions. Both connexins (40 and 45) showed a very low expression
      near the detection limit. The increases in connexin43 expression could be
      completely suppressed by SB203580 (0.9+/-0.4, P<0.05, n=5) but not by PD98059. In
      absence of a stimulating drug, these inhibitors (SB203580 or PD98059) did not
      affect connexin43 content. Additional PCR experiments revealed increases in
      connexin43 mRNA under the influence of 100 pg/ml TNFalpha (211+/-38%, P<0.05,
      n=5), which could be completely suppressed by SB203580. In contrast, the
      connexin40 expression remained unchanged. From these results, we conclude that
      TNFalpha can differentially regulate cardiac connexin expression via p38 MAP
      kinase pathway and thus may alter intercellular communication. This may
      contribute to the changes observed in heart failure with regard to the formation
      of an arrhythmogenic substrate.

PMID- 15496290
TI  - Investigation of extrinsic and intrinsic apoptosis pathways of new clerodane
      diterpenoids in human prostate cancer PC-3 cells.
AB  - In our continuing search to discover bioactive compounds from natural products,
      we isolated six new clerodane diterpenes, caseamembrins A to F, from Casearia
      membranacea and examined their antiproliferative activities in human hormone
      resistant prostate cancer PC-3 cells. All of these compounds displayed effective
      antiproliferative activity using sulforhodamine B assays and induced cell
      apoptosis by a terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling
      (TUNEL)-reaction technique. The data demonstrated that caseamembrin C was the
      most effective compound among these clerodane diterpenoids. Caseamembrin C
      induced down-regulation of Bcl-2 and Bcl-xL expression, while up-regulation of
      proapoptotic protein Mcl-1S (short chain), suggesting that these Bcl-2 family
      member proteins may play a role on arbitrating the apoptotic cell death.
      Caseamembrin C also induced the up-regulation of Fas ligand (FasL) expression,
      cleavage and activation of caspase-8 and caspase-9, Bid cleavage and activation
      of executor caspase-3. However, z-IETD-FMK (Z-Ile-Glu-Thr-Asp-fluoromethyl
      ketone, a selective caspase-8 inhibitor) almost completely inhibited caseamembrin
      C-induced Bid cleavage without any modification of caspase-9 activation,
      indicating that the extrinsic pathway of FasL/caspase-8/Bid cascade only played a
      minor role in the apoptotic signaling. Taken together, it is suggested that
      caseamembrin C-induced apoptosis is predominantly through the activation of
      intrinsic apoptosis pathways by causing the down-regulation of Bcl-2 and Bcl-xL
      expression, up-regulation of Mcl-1S protein and activation of caspase-9 and
      caspase-3.

PMID- 15496291
TI  - Different transport properties between famotidine and cimetidine by human renal
      organic ion transporters (SLC22A).
AB  - Histamine H2 receptor antagonist famotidine and cimetidine are commonly used for
      treatment of gastrointestinal ulcer diseases. Inasmuch as these drugs are mainly
      secreted by renal tubules, dosages have been adjusted according to renal
      function. Although many studies have been performed on the molecular mechanisms
      of renal handling of cimetidine, little is known about that of famotidine. In
      this study, to examine the recognition and transport of famotidine by human
      organic anion transporters (OATs; hOAT1, hOAT3) and human organic cation
      transporter (OCT; hOCT2), the uptake studies using Xenopus laevis oocytes were
      performed in comparison with cimetidine. The half-maximal inhibitory
      concentrations of famotidine for [3H]estrone sulfate transport by hOAT3 and
      [14C]tetraethylammonium transport by hOCT2 (300 microM and 1.8 mM, respectively)
      were higher than those of cimetidine (53 and 67 microM, respectively). While
      cimetidine inhibited p-[14C]aminohippurate transport by hOAT1 in a concentration
      dependent manner, famotidine did not affect it at 5 mM. In addition, hOAT3
      mediated famotidine uptake, but hOAT1 and hOCT2 did not show famotidine
      transport. These results indicate that there are marked differences between
      famotidine and cimetidine in the recognition and transport by organic ion
      transporters and that hOAT3 contributes to the renal tubular secretion of
      famotidine. Present findings should be useful information to understand the renal
      handling of famotidine and cimetidine.

PMID- 15496292
TI  - Effect of the flavonol quercetin on membrane conductances in rat colonic crypt
      cells.
AB  - The plant polyphenol quercetin was shown to induce Cl- secretion in rat colon.
      This study was performed to investigate the alterations of membrane conductances
      in isolated epithelial cells induced by quercetin. Whole-cell patch-clamp
      recordings were performed in isolated crypts from rat distal colon. In cells of
      the crypt basis, quercetin significantly hyperpolarized the membrane potential at
      concentrations > or =3 microM and increased the K+ conductance without visibly
      altering the Cl- conductance. Thus, quercetin induces Cl- secretion merely by
      activation of K+ channels in the colon epithelium.

PMID- 15496293
TI  - Locus coeruleus activity in perinatally protein-deprived rats: effects of
      fluoxetine administration.
AB  - We have previously described an increased locus coeruleus activity in perinatally
      protein-deprived rats. Since locus coeruleus dysfunction has been involved in
      different types of anxiety disorders and considering the modulating action of
      serotonergic transmission on locus coeruleus activity, we assessed the effect of
      fluoxetine, a selective serotonin reuptake inhibitor (SSRI), on locus coeruleus
      activity as measured by the firing rate and the number of spontaneously active
      cells/track. Repeated fluoxetine administration reduced locus coeruleus activity
      in both control and protein-deprived rats, although the reduction was greater in
      protein-deprived rats. Dose-response curves for the inhibitory effect of
      clonidine showed subsensitivity of alpha2-adrenergic autoreceptors in protein
      deprived rats, a phenomenon reversed by fluoxetine treatment. Dose-response
      curves for the inhibitory effect of 2,5-dimethoxy-4-iodoamphetamine (DOI) were
      similar in both groups of rats. Following fluoxetine administration,
      subsensitivity to this effect developed in control but not in protein-deprived
      rats. Extracellular noradrenaline level in the prefrontal cortex, as measured by
      microdialysis procedure, was higher in protein-deprived rats compared to
      controls, and this difference was reduced after fluoxetine administration. A
      challenge with yohimbine increased the extracellular noradrenaline level in
      control but not in protein-deprived rats, suggesting subsensitivity of alpha2
      adrenergic autoreceptors in early protein malnourished animals. These results
      stress the complexity of plastic changes induced by early protein malnutrition
      and sustain the hypothesis that perinatally protein-deprived rats may represent a
      useful animal model for screening antipanic agents.

PMID- 15496294
TI  - Peripheral involvement of the nitric oxide-cGMP pathway in the indomethacin
      induced antinociception in rat.
AB  - The role of nitric oxide (NO) in the antinociceptive effect of indomethacin was
      assessed in the pain-induced functional impairment model in the rat (PIFIR
      model), a model of inflammatory and chronic pain similar to that observed in
      clinical gout. Oral administration of indomethacin (5.6 mg/kg), a nonselective
      cyclooxygenase inhibitor, significantly decreased the nociceptive response
      elicited by uric acid injected into the knee joint of the right hind limb (2.0+/
      3.0 and 149.7+/-18.0 area units [au], in the absence and the presence of
      indomethacin, respectively). This effect of indomethacin was reduced in nearly
      50% by local pretreatment with the nonselective inhibitor of NO synthase, N G-L
      nitro-arginine methyl ester (L-NAME) (72.9+/-10.7 vs. 149.7+/-18.0 au, P<0.05).
      On the other hand, local administration of L-arginine (a NO synthase substrate)
      or sodium nitroprusside (a non-enzymatic NO donor) each increased in almost 40%
      the antinociceptive effect of indomethacin (230.9+/-12.6 and 226.6+/-9.7 vs.
      149.7+/-18.0 au, P<0.05), whereas D-arginine (the inactive isomer of arginine)
      had no effect on the indomethacin antinociceptive response (208.0+/-34.9 vs.
      149.7+/-18.0 au). These results suggest that, the antinociceptive effect of
      indomethacin involves, at least in part, the NO-cyclic GMP pathway at peripheral
      level.

PMID- 15496295
TI  - General anesthetics inhibit the nitrous-oxide-induced activation of corticotropin
      releasing factor containing neurons in rats.
AB  - The activation of intracerebral corticotropin releasing factor (CRF) system is
      involved in nitrous oxide analgesia. We evaluated the effect of general
      anesthetics on nitrous-oxide-induced CRF activation and antinociception. Male
      Sprague-Dawley rats inhaled isoflurane (0%, 0.6%, 1.0% and 1.5%) or were
      administered with intravenous propofol (0, 0.1 and 0.2 mg/kg/min), with or
      without 75% nitrous oxide inhalation, for 90 min. The brain was fixed with
      fixative, and brain sections, including the paraventricular nucleus of the
      hypothalamus, were double immunostained with c-Fos and CRF antibodies to assess
      the activation of CRF-containing neurons. In other groups of rats, the effect of
      propofol on nitrous oxide antinociception was evaluated with tail flick latency
      tests. Both inhaled isoflurane and intravenous propofol inhibited nitrous-oxide
      induced activation of CRF neurons, suggesting that these general anesthetics may
      inhibit one of the analgesic mechanisms of nitrous oxide. Indeed, propofol
      inhibited the antinociceptive action of nitrous oxide, as evaluated with tail
      flick latencies (TFL).

PMID- 15496296
TI  - Endogenously released 5-hydroxytryptamine depresses the spinal monosynaptic
      reflex via 5-HT1D receptors.
AB  - In the spinal cord, various 5-hydroxytryptamine (5-HT) receptor subtypes are
      involved in the modulation of motor output. Previously, we have shown that 5-HT1B
      receptors mediate the monosynaptic reflex depression induced by exogenously
      applied 5-HT that was formed from the precursor L-5-hydroxytryptophan in
      spinalized rats. In this study, we determined the effects of endogenous 5-HT,
      which was released from serotonergic terminals by DL-p-chloroamphetamine, on
      spinal reflexes. DL-p-chloroamphetamine depressed the monosynaptic reflex and
      increased the polysynaptic reflex. The depletion of 5-HT abolished the
      monosynaptic reflex depression, but the increase in polysynaptic reflexes was
      maintained, suggesting that endogenous 5-HT released by DL-p-chloroamphetamine
      mediates depression of the monosynaptic reflex in the spinal cord. The depression
      of the monosynaptic reflex was antagonized by GR127935 (N-[methoxy-3-(4-methyl-l
      piperazinyl)phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)[1,1-biphenyl]-4
      carboxamide; 5-HT1B/1D receptor antagonist) and BRL15572 (3-[4-(4
      chlorophenyl)piperazin-1-yl]-1,1-diphenyl-2-propanol; 5-HT1D receptor antagonist)
      but not by isamoltane (5-HT(1B) receptor antagonist). These results suggest that
      5-HT released from serotonergic terminals depresses monosynaptic reflex
      transmission via 5-HT1D receptors.

PMID- 15496297
TI  - Role of the histamine system in nefopam-induced antinociception in mice.
AB  - The present study explored the role of the histaminergic system in nefopam
      analgesia based on the structural relationship between nefopam and
      diphenhydramine. In vitro binding assays revealed that nefopam possesses moderate
      affinity for histamine H1 and H2 receptor subtypes, with IC50 of 0.8 and 6.9
      microM, respectively, but no affinity for histamine H(3) receptor subtype until
      100 microM. Subcutaneous nefopam administration dose-dependently inhibited pain
      in acetic acid-induced writhing (1-30 mg/kg) and formalin (1-10 mg/kg) tests in
      the mouse. Pretreatment with the histamine-depleting agent alpha
      fluoromethylhistidine (alpha-FMH, 50 mg/kg), the histamine H1 receptor antagonist
      pyrilamine (3 or 10 mg/kg), or the histamine H2 receptor antagonists cimetidine
      (100 mg/kg) and zolantidine (10 or 30 mg/kg) did not significantly modify nefopam
      antinociception in both tests. The histamine H3 receptor agonist R(-)alpha
      methylhistamine (RAMH, 10 mg/kg) did not significantly modify the nefopam
      analgesic activity in the writhing test. At 25 mg/kg, RAMH inhibited nefopam
      antinociception at 3 mg/kg, but not at 10 mg/kg in the formalin test. However,
      pretreatment with the histamine H3 receptor antagonist thioperamide (25 mg/kg)
      inhibited nefopam antinociception in the writhing test, but not in the formalin
      test. In conclusion, nefopam analgesic activity is not mediated by histamine H1
      or H2 receptors, but can be slightly modulated by histamine H3 receptors in mouse
      pain tests.

PMID- 15496298
TI  - Characterization of N-methyl-D-aspartate receptor subunits responsible for
      postoperative pain.
AB  - N-methyl-D-aspartate (NMDA) receptors have been suggested to be critical for the
      development of central sensitization, which may amplify postoperative pain. NMDA
      receptors are formed by GluRzeta (NR1) with any one of four GluRvarepsilon1-4
      (NR2A-D) subunits. To clarify the involvement of NMDA receptors in postoperative
      pain, we examined the effect of the GluRepsilon2-selective antagonist (1S,2S)-1
      (4-hydroxyphenyl)-2-(4-hydroxy-4-phenyl piperidino)-1-propanol (CP-101,606) on
      postoperative pain caused by plantar incision. We also applied the postoperative
      pain model to GluRepsilon1 and GluRepsilon4 knockout mice. CP-101,606
      administered intrathecally 30 min prior to incision significantly increased
      mechanical withdrawal thresholds 2 h and 1-3 days after surgery and reduced
      postoperative pain dose-dependently. Neither GluRvarepsilon1 nor GluRepsilon4
      knockout mice showed a difference in withdrawal thresholds as compared with wild
      type mice. Pretreatment with CP-101,606 did not produce an additive analgesic
      effect in the mice. These results demonstrate that GluRepsilon2-containing NMDA
      receptors are involved in postoperative pain and that CP-101,606 may be effective
      in reducing it.

PMID- 15496299
TI  - Protection by the GABAB receptor antagonist, SCH 50911, of gamma-hydroxybutyric
      acid-induced mortality in mice.
AB  - Different effects of moderate to high doses of gamma-hydroxybutyric acid,
      including sedation/hypnosis, have been found to be blocked by gamma-aminobutyric
      acidB (GABAB) receptor antagonists. The present study investigated whether the
      protective effect of GABAB receptor antagonists extends also to gamma
      hydroxybutyric acid-induced mortality. To this aim, the present study
      investigated the effect of the GABAB receptor antagonist, (2S)(+)-5,5-dimethyl-2
      morpholineacetic acid (SCH 50911; 100 mg/kg, ip), on mortality induced by gamma
      hydroxybutyric acid (1-6 g/kg, ip) in DBA mice. Pretreatment with SCH 50911
      resulted in a significant shift to the right of the dose-response curve of gamma
      hydroxybutyric acid-induced mortality. Accordingly, the LD50 in SCH 50911
      pretreated mice was significantly higher than that obtained in water-pretreated
      mice. The results of the present study support the hypothesis that (a) the GABAB
      receptor is a relevant site of action of gamma-hydroxybutyric acid, and (b) GABAB
      receptor antagonists may constitute potentially effective therapeutic
      interventions for gamma-hydroxybutyric acid intoxication.

PMID- 15496300
TI  - The effects of nitric oxide on the acquisition and expression of nicotine-induced
      conditioned place preference in mice.
AB  - In the present study, the possible role of nitric oxide on the conditioned place
      preference (CPP) induced by nicotine in mice was investigated. Intraperitoneal
      (i.p.) injections of nicotine (1 mg/kg) and the nitric oxide (NO) precursor, L
      arginine (200 and 500 mg/kg), produced significant place preference. However,
      injection of mecamylamine (0.05 and 0.1 mg/kg; i.p.) or the NO synthase (NOS)
      inhibitor, L-Nitro-amino-methyl-ester, L-NAME (5-20 mg/kg; i.p.), had no effect.
      Ineffective doses of nicotine in combination with ineffective doses of L-arginine
      produced significant place preference. Administration of L-arginine (50, 100 and
      150 mg/kg; i.p.) on the test day reduced the expression of nicotine-induced place
      preference. Nicotine injection (0.25, 0.5 and 0.75 mg/kg) on the test day reduced
      the expression of place preference induced by L-arginine, while both mecamylamine
      (0.05 and 0.1 mg/kg) and L-NAME (5, 10 and 20 mg/kg) inhibited the acquisition of
      place preference induced by nicotine (1 mg/kg) and L-arginine (200 mg/kg).
      Moreover, neither of the antagonists reduced the expression of nicotine- or L
      arginine-induced place preference. It is suggested that nitric oxide may play an
      important role in nicotine-induced place preference.

PMID- 15496301
TI  - The effects of intraperitoneal and intracerebroventricular administration of the
      GABAB receptor antagonist CGP 35348 on food intake in rats.
AB  - In order to test the hypothesis that endogenous gamma-aminobutyric acid (GABA),
      acting at central GABAB receptors, plays a physiological role in the control of
      feeding behaviour, it was reasoned that blocking these receptors with a centrally
      active GABAB receptor antagonist should reduce food intake in hungry rats. In the
      present study, experiments were carried out to test this possibility using the
      GABAB receptor antagonist 3-aminopropyl-diethoxy-methyl-phosphinic acid (CGP
      35348), which is water-soluble and can penetrate the blood-brain barrier from the
      systemic circulation. CGP 35348 (50 and 100 mg/kg, i.p.) had no effect on food
      intake in 22-h fasted rats, but a higher dose (i.e. 500 mg/kg., i.p.)
      significantly reduced cumulative food consumption. These findings are consistent
      with previous observations that high systemic doses of CGP 35348 are needed to
      block central GABAB receptors. However, to eliminate the possibility that the 500
      mg/kg dose of CGP 35348 decreased food intake by a peripheral, rather than a
      central mode of action, further experiments were undertaken where the drug was
      given directly into the brain by the intracerebroventricular (i.c.v.) route.
      I.c.v. administration of CGP 35348 (5 and 10 microg) significantly decreased
      cumulative food intake food intake in rats that had been fasted for 22 h. By
      contrast, i.c.v. administration of CGP 35348 (10 microg) had no effect on water
      intake in 16-h water-deprived rats. The results indicate that CGP 35348 reduces
      food consumption in hungry rats by blocking central GABAB receptors in a
      behaviourally specific manner. These findings suggest that endogenous GABA acting
      at central GABAB receptors plays a physiological role in the regulation of
      feeding behaviour.

PMID- 15496302
TI  - Effect of neramexane on ethanol dependence and reinforcement.
AB  - It has been suggested that drugs modulating the glutamate/N-methyl-D-aspartate
      (NMDA) receptor system may be useful in the treatment of alcohol dependence. The
      effect of neramexane, a low-to-moderate affinity uncompetitive NMDA receptor
      antagonist, was examined on the development and expression of ethanol dependence
      (withdrawal-associated audiogenic seizures) and ethanol-induced conditioned place
      preference. Neramexane hydrochloride (3.5 mg/kg and higher) inhibited both the
      development and expression of ethanol dependence. Neramexane hydrochloride also
      inhibited the acquisition (1.75 mg/kg and higher) and expression (3.5 mg/kg and
      higher) of ethanol-induced place preference. Our data support therapeutic
      potential of neramexane as a treatment for alcohol abuse.

PMID- 15496303
TI  - Ondansetron, given during the acute cocaine withdrawal, attenuates oral cocaine
      self-administration.
AB  - We have previously shown that ondansetron, given 3.5 h after intravenous cocaine
      self-administration, can attenuate self-administration the following day. Here we
      tested ondansetron given either before or after a 14-h oral cocaine session in
      rats. Ondansetron (0.2 mg/kg sc) given 30 min before the cocaine session had no
      effect. However, when given 3.5 h after, ondansetron attenuated cocaine intake
      the following day while having no effect on water intake. Taken with our previous
      data in intravenous cocaine self-administration, we suggest that the acute
      cocaine withdrawal period may be an important treatment window and that
      ondansetron may be an effective cocaine abuse therapy.

PMID- 15496304
TI  - The neuronal selective nitric oxide synthase inhibitor, Nomega-propyl-L-arginine,
      blocks the effects of phencyclidine on prepulse inhibition and locomotor activity
      in mice.
AB  - Phencyclidine has frequently been used to model schizophrenia in animals. In the
      present study, the ability of the neuronal selective nitric oxide synthase (NOS)
      inhibitor, Nomega-propyl-L-arginine, to block the behavioural effects of
      phencyclidine in mice was investigated. N(omega)-propyl-L-arginine (20 mg/kg) was
      found to block both phencyclidine (4 mg/kg)-induced disruption of prepulse
      inhibition and phencyclidine-induced stimulation of locomotor activity in the
      mice tested. It is concluded that the NOS-sensitive behavioural effects of
      phencyclidine in rodents is dependent on neuronal NOS and that NO may play a role
      in the psychotomimetic effects of phencyclidine.

PMID- 15496305
TI  - Differences in the effects of Na+-H+ exchange inhibitors on cardiac function and
      apoptosis in guinea-pig ischemia-reperfused hearts.
AB  - The protective effects of the Na+-H+ exchange (NHE) inhibitors SM-198110 (2
      [[(aminoiminomethyl) amino] carbonyl]-4-chloro-1H-indole-1-propanesulfonic acid
      monohydrate) and SM-197378 (N-(aminoiminomethyl)-1-methyl-7-(sulfooxy)-4
      (trifluoromethyl)-1H-indole-2-carboxamide monohydrate) were investigated in
      perfused Langendorff guinea-pig hearts subjected to ischemia (40 min) and
      reperfusion (40 min). The recovery of left ventricular developed pressure (LVDP)
      from ischemia by reperfusion was 39.0% in the control, while in the hearts
      pretreated with SM-198110 or SM-197378 (10(-7) M), it was about 100%. The ATP
      level, monitored simultaneously by (31)P-nuclear magnetic resonance spectrometry,
      was already higher than the control value at the end of the ischemic period, and
      the elevation in Na+ or Ca2+ fluorometric signals induced during ischemia was
      suppressed. In post-treated hearts, the LVDP recovery rate was significantly
      higher with SM-198110 than with SM-197378. By in vitro electron paramagnetic
      resonance spectrometry, SM-197378 was found to directly quench the active oxygen
      radical, whereas SM-198110 had no effect. Numbers of apoptotic cardiomyocytes
      after ischemia (1 h) followed by reperfusion (5 h) were significantly lower in SM
      197378-treated than in SM-198110-treated hearts, consistent with the level of
      activity of caspase-3. These results suggest that the antioxidant effects of NHE
      inhibitors have an important role in apoptosis during ischemia-reperfusion, but
      apoptosis is not a major manifestation of cardiac function during postischemic
      recovery, and that NHE-sensitive mechanisms of reperfusion injury promote both
      necrotic and apoptotic processes death.

PMID- 15496306
TI  - Protective effect of trimetazidine on myocardial mitochondrial function in an ex
      vivo model of global myocardial ischemia.
AB  - Trimetazidine is an anti-ischemic drug whose cytoprotective mechanisms are not
      yet fully understood (but until now mainly related to the trimetazidine-induced
      "metabolic shift" from lipid beta-oxidation to glucose aerobic oxidation). We
      studied the effect of trimetazidine on the mitochondrial function of ischemic
      Wistar rat hearts perfused with glucose, using a model of ex-vivo perfusion
      (Langendorff system). We measured the electrical potential of the mitochondrial
      membrane, O2 consumption by the respiratory chain, energy charges generated and
      the enzyme activities of the respiratory chain complexes. In this model,
      trimetazidine had a preferential action on the oxidative system (mainly on
      complex I), increasing its enzyme activity and decreasing O2 consumption after
      phosphorylation; this could decrease oxygen free radical production and increase
      mitochondrial integrity, thus allowing the maintenance of the electrical
      potential. These results allow us to better understand the cytoprotective effects
      of trimetazidine in coronary artery disease.

PMID- 15496307
TI  - Control of vascular changes by renin-angiotensin-aldosterone system in salt
      sensitive hypertension.
AB  - The purpose of this study was to investigate the role of the renin-angiotensin
      aldosterone system in hypertension development and cardiovascular structural
      changes in a salt-sensitive hypertensive model induced by capsaicin (CAP).
      Newborn male Wistar rats were injected with either capsaicin or vehicle. After
      weaning at 3 weeks, these rats were divided into the following six treatment
      groups: capsaicin plus high-salt diet (CAP+HS), control plus high-salt diet
      (CON+HS), control plus normal salt diet (CON+NS), capsaicin plus high-salt diet
      and telmisartan (CAP+HS+T, 10 mg/kg/day), capsaicin plus high-salt diet and
      perindopril (CAP+HS+P, 2 mg/kg/day), and capsaicin plus high-salt diet and
      spironolactone (CAP+HS+S, 80 mg/kg/day). Treatment with different salt diets and
      drugs was initiated at 3 weeks of age and lasted 18 weeks. We found that
      beginning at the second week after the initiation of the treatment, blood
      pressure became significantly higher in CAP+HS than in other groups, accompanied
      by the development of cardiac hypertrophy. Treatment with telmisartan,
      perindopril or spironolactone prevented the development of hypertension in the
      CAP+HS group. Cardiac hypertrophy was prevented in the perindopril treatment
      group. The medial thickness, media-to-lumen ratio and cross-sectional area of the
      thoracic, renal and mesenteric arteries were significantly increased in CAP+HS
      than in other groups. Lumen diameter was similar in all the vessels among all the
      groups. Treatment with telmisartan, perindopril or spironolactone prevented the
      development of vascular remodeling, as found in the CAP+HS group. Beginning at 8
      weeks after the initiation of the salt diet treatment (11 weeks of age), blood
      pressure also became higher in CON+HS than in CON+NS, but lower than CAP+HS.
      Structural changes of vessels were also present in CON+HS, but the degree of
      change was less when compared with CAP+HS. We conclude that neonatal treatment
      with capsaicin plus a high-salt diet, and a high-salt diet alone both induced
      hypertension development in normal Wistar rats, which are associated with
      cardiovascular remodeling. The renin-angiotensin-aldosterone system is involved
      in this salt-sensitive model because treatment that interfered with this system
      also prevented the development of hypertension and vascular remodeling.

PMID- 15496308
TI  - Effects of trimetazidine on myocardial preconditioning in anesthetized rats.
AB  - Trimetazidine is a widely used anti-ischemic agent, but its effect on myocardial
      preconditioning in anesthetized animals has not been investigated. The aim of
      this study was to examine the effects of trimetazidine on ischemic
      preconditioning and carbachol preconditioning in anesthetized rats. Ischemic
      preconditioning, induced by 5-min coronary artery occlusion and 5-min
      reperfusion, decreased the incidence of ventricular tachycardia and abolished the
      occurrence of ventricular fibrillation during 30-min ischemia. Trimetazidine (10
      mg/kg, i.v.) alone attenuated these parameters of arrhythmia. Carbachol infusion
      induced preconditioning with a marked depression of mean arterial blood pressure,
      heart rate and ventricular tachycardia. The marked reductions in parameters of
      arrhythmia induced by ischemic preconditioning and carbachol preconditioning were
      preserved in the presence of trimetazidine. Arrhythmia scores and myocardial
      infarct size were significantly reduced with ischemic preconditioning or
      carbachol preconditioning and were not inhibited by trimetazidine. These results
      show that trimetazidine protects the heart against ischemia-induced arrhythmias,
      reduces myocardial infarct size, preserves the effects of ischemic
      preconditioning and pharmacological preconditioning, and is able to mimic
      ischemic preconditioning in anesthetized rats.

PMID- 15496309
TI  - Ischemic heart disease down-regulates angiotensin type 1 receptor mRNA in human
      coronary arteries.
AB  - Angiotensin II is important in the development of cardiovascular disease. In the
      present study, angiotensin II receptor mRNA levels were quantified by real-time
      polymerase chain reaction (real-time PCR) in human coronary arteries from
      patients with ischemic heart disease and controls. Furthermore, the suitability
      of artery culture for studying angiotensin receptor changes was evaluated by in
      vitro pharmacology and real-time PCR. The angiotensin type 1 (AT1) receptor mRNA
      levels were down-regulated in human coronary arteries from patients with ischemic
      heart disease as compared to controls (P<0.05). Culture of coronary arteries for
      48 h induced down-regulation of the angiotensin AT1 and AT2 receptor mRNA levels
      and also a less efficacious angiotensin II-induced vasoconstriction (Emax=103+/
      2% before and 23+/-7% after artery culture, P<0.001). Artery culture may thus be
      a suitable method for studying angiotensin receptor regulation.

PMID- 15496310
TI  - Pharmacological characterization of alpha1-adrenoceptors in mouse isolated
      femoral small arteries.
AB  - Arteries were isolated from male DBA/2 mice and mounted on a small vessel wire
      myograph for isometric recording. Responses to exogenous noradrenaline were
      inhibited with high affinity by prazosin (pKB, 9.3) and 5-methyl-urapidil (pKB,
      9.2) and with low affinity by 8-[2-[4-(2-methoxyphenyl)-1 piperazinyl]ethyl]-8
      azaspiro[4.5]decane-7,9-dione (BMY 7378) (pA(2), 6.7). Chloroethylclonidine (10
      microM) produced only a small reduction in the maximum response to noradrenaline.
      Responses to electrical field stimulation were also inhibited with high affinity
      by prazosin (pIC50, 9.3-9.5) and 5-methyl-urapidil (pIC50, 8.0-8.3). Responses
      were sensitive to BMY 7378 at low frequencies of stimulation (pIC50 at 2 Hz, 8.2)
      but not at high frequencies (pIC50 at 20 Hz, 6.5). In conclusion, contractions to
      exogenous and endogenous noradrenaline in mouse femoral small arteries are
      mediated mainly by alpha1A-adrenoceptors. alpha1D-adrenoceptors are not involved
      in responses to exogenous noradrenaline but appear to be activated by neurally
      released noradrenaline at a low frequency of stimulation.

PMID- 15496311
TI  - Genistein reduces agonist-induced contractions of porcine coronary arterial
      smooth muscle in a cyclic AMP-dependent manner.
AB  - Low concentrations of genistein enhance the vasodilatation induced by endothelium
      independent vasodilators. The present study examined whether or not low
      concentrations of genistein modulate contractions in isolated porcine coronary
      arteries. The role of second messengers in the response to genistein was also
      assessed. Arterial rings were studied in organ baths and contracted with KCl, U
      46619 (9,11-dideoxy-9alpha, 11alpha-methanoepoxy prostaglandin F2alpha), 5
      hydroxytryptamine (5-HT) or endothelin-1 in the absence or presence of genistein
      (< or =3 microM). Genistein significantly reduced agonist-induced but not KCl
      induced contraction. Inhibition of endothelial nitric oxide synthase and
      disruption of endothelial function by Triton-X100 did not affect the modulation
      of contraction by genistein. The genistein-induced attenuation of contraction
      could be mimicked by both cAMP and cGMP analogs. However, only the cAMP-dependent
      protein kinase inhibitor, Rp-8-Br-cAMPS, abolished the effect of genistein. These
      results suggest that genistein reduces agonist-induced contraction by an
      endothelium-independent manner. This action is mediated via the cAMP-dependent
      signal transduction pathway.

PMID- 15496312
TI  - Differential effects of caspase inhibitors on the renal dysfunction and injury
      caused by ischemia-reperfusion of the rat kidney.
AB  - Caspase activation has been implicated in the development of ischemia-reperfusion
      injury. Here, we investigate the effects of different caspase inhibitors on the
      renal dysfunction and injury caused by ischemia-reperfusion of the rat kidney.
      Bilateral clamping of renal pedicles (45 min) followed by reperfusion (6 h)
      caused significant renal dysfunction and marked renal injury. Caspase-1 inhibitor
      II (N-acetyl-L-tyrosyl-L-valyl-N-[(1S)-1-(carboxymethyl)-3-chloro-2-oxo-propyl]-L
      alaninamide, Ac-YVAD-CMK, 3 mg/kg, administered i.p.) significantly reduced
      biochemical and histological evidence of renal dysfunction and injury. However,
      although caspase-3 inhibitor I (N-acetyl-L-aspartyl-L-glutamyl-N-(2-carboxyl-1
      formylethyl]-L-valinamide, Ac-DEVD-CHO, 3 mg/kg, administered i.p.) produced a
      significant improvement of renal (glomerular) dysfunction (reduction of serum
      creatinine levels), it was not able to reduce tubular dysfunction and injury.
      Furthermore, the pan-caspase inhibitor caspase inhibitor III (N-tert
      butoxycarbonyl-aspartyl(OMe)-fluoromethylketone, Boc-D-FMK, 3 mg/kg, administered
      i.p.) did not reduce renal dysfunction and injury. Both caspase-1 and -3
      inhibitors markedly reduced the evidence of oxidative and nitrosative stress in
      rat kidneys subjected to ischemia-reperfusion. Overall, these results demonstrate
      that inhibition of caspase-1 reduces renal ischemia-reperfusion injury to a
      greater extent than caspase-3 inhibition, supporting the notion that the mode of
      acute cell death in our model of renal ischemia-reperfusion is primarily via
      necrosis. Furthermore, our finding that a pan-caspase inhibitor did not reduce
      the renal dysfunction and injury suggests that activation of some caspases during
      ischemia-reperfusion could provide protection against acute ischemic renal
      injury. Overall, these results demonstrate that inhibition of caspase-1 activity
      reduces renal ischemia-reperfusion injury and that this therapeutic strategy may
      be of benefit against ischemic acute renal failure.

PMID- 15496313
TI  - The kappa-opioid receptor agonist asimadoline inhibits epithelial transport in
      mouse trachea and colon.
AB  - The potent kappa-opioid receptor agonist n-methyl-N-[(1S)-1-phenyl-2-((3S)-3
      hydroxypyrrolidin-1-yl)-ethyl]-2,2-diphenyl-acetamide hydrochloride (asimadoline,
      EMD 61753) was initially developed for the treatment of chronic pain. Because
      opioids are well known to reduce secretion and to cause constipation, we
      investigated the effects on epithelial transport in murine trachea and colon. In
      Ussing chamber experiments, asimadoline (100 microM) decreased short-circuit
      currents in airways and colon epithelium. The inhibition of I(SC) was not blocked
      by naloxone (10 microM) or nor-binaltorphimine (10 microM), suggesting that the
      response was not mediated by kappa-opioid receptors. The effect of asimadoline on
      I(SC) was concentration-dependent with half-maximal inhibition of I SC at 23.7
      (9.5-49.3) microM and was sensitive to the K+ channel blocker charybdotoxin (10
      nM). The amiloride-sensitive Na+ current was reduced by asimadoline, but not in
      cAMP stimulated tissues. Asimadoline strongly inhibited transient Ca2+-dependent
      Cl- secretion, activated by the muscarinic receptor agonist carbachol (100
      microM) or the purinergic agonist ATP (100 microM). Thus, asimadoline inhibits
      epithelial transport independent of kappa-opioid receptors, by inhibition of
      basolateral Ca2+-activated and charybdotoxin-sensitive K+ channels.

PMID- 15496314
TI  - Enhancement of purinergic neurotransmission by galantamine and other
      acetylcholinesterase inhibitors in the rat vas deferens.
AB  - Galantamine, a mild acetylcholinesterase inhibitor and an allosteric ligand of
      nicotinic receptors, enhanced in a concentration-dependent manner the amplitude
      of purinergic twitch contractions of the electrically stimulated rat vas deferens
      (0.2 Hz, 1 ms, 60 V). Other acetylcholinesterase inhibitors also increased the
      twitches, showing a hierarchy of potencies of
      galantamine>physostigmine>tacrine>rivastigmine=donepezil. The potentiations seem
      to be unrelated to the ability to inhibit acetylcholinesterase, since the
      hierarchy of potencies to block the enzyme in vas deferens was
      tacrine>physostigmine>rivastigmine>donepezil>galantamine. Acetylcholine also
      increased the twitches; such effect was produced by a low range of concentrations
      of acetylcholine (10(-10)-10(-7) M). This facilitatory effect of acetylcholine on
      twitches was significantly potentiated by galantamine (10(-7)-10(-6) M), but not
      by rivastigmine or donepezil. A striking enhancement of twitches was also caused
      by charybdotoxin, a blocker of high-conductance Ca2+-activated K+ channels, and
      by 4-aminopyridine, a non-specific blocker of K+ channels; in addition, apamin, a
      blocker of small-conductance Ca2+-activated K+ channels, induced a lower
      potentiation. The antagonist mecamylamine (10(-7)-10(-6) M) reduced by 80% the
      potentiation by galantamine, indicating the involvement of nicotinic receptors.
      Therefore, it is suggested that, besides an inhibition of acetylcholinesterase,
      some additional mechanisms, such as blockade of Ca2+-dependent K+ channels, or
      activation of nicotinic receptors of nerve terminals, might be involved in twitch
      potentiation. These results are relevant in the context of the clinical use of
      galantamine to improve cognition and behaviour in patients with Alzheimer's
      disease.

PMID- 15496316
TI  - Opioid receptors and acetaminophen (paracetamol).
AB  - We report that the acetaminophen (paracetamol)-induced spinal (intrathecal,
      i.t.)/supraspinal (intracerebroventricular, i.c.v.) site/site antinociceptive
      'self-synergy' in mice is attenuated by the opioid receptor subtype selective
      antagonists beta-funaltrexamine hydrochloride (beta-FNA; mu), naltrindole
      (delta), and nor-binaltorphine hydrochloride (nor-BNI; kappa). These findings
      further implicate endogenous opioids (viz., endorphins, enkephalins, and
      dynorphins) and their pathways as contributors to the central antinociceptive
      action of acetaminophen.

PMID- 15496315
TI  - Titanocene modulation of cytokine imbalance induced by Ehrlich ascites tumour
      progression.
AB  - In the present work, we have studied the effects of two titanocenes,
      biscyclopentadienyldichlorotitanium IV (DDCT) and its derivative,
      biscyclopentadienylditiocianatetitanium IV (BCDT), on the production of cytokines
      [interferon-gamma (IFN-gamma), interelukin-1, interleukin (IL) 2, IL-4, and IL
      10] by concanavalin A (Con A)-stimulated T cells obtained from Ehrlich ascites
      tumour (EAT)-bearing BALB/c mice. The treatment consisted of intraperitoneal
      (i.p) administration of 15 mg/kg/day DDCT for 2 days or 10 mg/kg/day BCDT for 3
      days. We observed that the levels of IFN-gamma, but not IL-2, were dramatically
      increased in the early phase of EAT development. With tumour evolution, however,
      a sharp and progressive decrease in the levels of both IFN-gamma and IL-2 was
      found concomitantly to an enhancement in the levels of IL-10. Treatment of these
      mice with both titanocene compounds demonstrated that DDCT is more effective in
      modulating the cytokine imbalance induced by the tumour since it could prevent
      the early enhancement of IFN-gamma, the late decline of IFN-gamma and IL-2, and
      the increase in the IL-10. The administration of BCDT, in spite of preventing
      early IFN-gamma enhancement and increase in IL-10, did not produce any change in
      the IL-2 levels and did not prevent the decline of IFN-gamma levels during tumour
      evolution. Collectively, these results reveal that the ability of titanocenes to
      reverse tumour-induced immunosuppression and delay tumour growth is more evident
      in the DDCT compound, thus indicating that the substitution of the halides
      halogens by pseudohalogens, present in the molecular structure of BCDT, leads to
      a less effective antitumoral compound.

PMID- 15496317
TI  - UV spectroscopy and reverse-phase HPLC as novel methods to determine Capreomycin
      of liposomal fomulations.
AB  - Capreomycin (CS) is an antitubercular drug active against several Mycobacterium
      strains, in particular, against M. Avium. In spite of its activity, it is
      considered a second line drug because it can induce severe renal and hepatic
      damages when administered as free drug. However, it is possible to employ drug
      delivery systems, such as liposomes, to reduce the toxicity of the peptide
      without loss of its biological activity. For this purpose, appropriately
      validated time and money saving analytical methods are needed for a careful
      capreomycin dosage. In the present paper, UV spectroscopy and a reverse-phase
      HPLC (RP-HPLC) were investigated as alternative methods for capreomycin
      quantitative analysis. These techniques were validated against the USP XXVI
      microbiological turbidimetric assay and the normal-phase HPLC (NP-HPLC) method
      reported in the British Pharmacopoeia 2003. The results obtained showed that
      either UV spectrophotometry or RP-HPLC are techniques having higher accuracy and
      reproducibility with respect to the microbiological assay. Moreover, the RP-HPLC
      method provided improved performances if compared to NP-HPLC. In fact, RP-HPLC
      showed: (i) enhanced sensitivity and (ii) increased resolution. Thus we propose
      RP-HPLC and UV as valid alternative methods to the conventional procedures for
      capreomycin quantitative analysis.

PMID- 15496318
TI  - Fast separation of bacitracin on monolithic silica columns.
AB  - The development of isocratic and gradient stability indicating HPLC methods for
      bacitracin (Bc) and bacitracin zinc (BcZn), which are complex mixture of several
      related polypeptides, is described. The methods are based on a new type of
      reversed phase (RP-18e) monolithic silicagel stationary phase. Chromatographic
      experimental conditions used on conventional column with microparticles were
      adopted and further modified to achieve efficient separation of Bc. The influence
      of methanol and acetonitrile in combination with phosphate buffer was thoroughly
      studied to separate microbiologically active components A, B1, B2, B3 and their
      oxidative degradation products F, H1, H2 and H3. Chromatographic peaks of all the
      mentioned components were identified using compounds isolated previously by
      preparative HPLC. Applying isocratic or gradient approach, highly efficient
      separation was achieved together with drastically reduced analysis times (ca. 6
      min) compared to all published HPLC methods up to date. With thus developed HPLC
      methods, it is possible to evaluate not only the main degradation product F, but
      for the first time also several other oxidative degradation products of Bc (H1,
      H2 and H3). Such methods are also suitable for routine quality control and
      stability testing. Validation of both isocratic and gradient methods confirmed
      the selectivity and efficiency comparable to that on microparticulate columns,
      yet contrary to conventional columns with highly reduced analysis time.

PMID- 15496319
TI  - Identification of low-level degradants from low dose tablets.
AB  - A multifaceted approach was successfully used to identify three of four unknown
      degradants in degraded low dose tablets. Accelerated solvent extraction (ASE) was
      found to be an invaluable tool in this multifaceted approach. ASE was capable of
      extracting four individual degradants of an active pharmaceutical component from
      10 tablets into 15 mL of solvent with approximately 100% recovery for each
      degradant. Using ASE instead of manual extraction led to the extraction and
      isolation of the degradants in 1 day instead of 7 days. One of the degradants was
      extracted by ASE, isolated by semi-prep HPLC, and identified by LC-MS and NMR
      spectroscopy. The structures of two of the remaining three degradants were
      confirmed by synthesis of authentic samples, while the fourth degradant is yet to
      be identified.

PMID- 15496320
TI  - Rapid analysis of liquid formulations containing sodium chloride using laser
      induced breakdown spectroscopy.
AB  - The purpose of this work was to demonstrate the possibilities offered by laser
      induced breakdown spectroscopy (LIBS) for the direct and rapid analysis of
      pharmaceutical liquid formulations. Sodium chloride in solution was chosen as a
      model compound. A pulsed Nd:YAG laser (1064 nm) was used to produce a gaseous
      plasma from the liquid sample. The ensuing plasma emission was spectrally
      analysed, and the intensity of an atomic line from sodium was used to quantitate
      the sodium chloride. Using surface analysis of a flowing solution, the precision
      (%R.S.D.) of a measurement lasting 50 s (average of 50 laser shots at 1 shot/s)
      was approximately 0.5% for isotonic solutions. On a non-flowing solution, a 50 s
      measurement had an R.S.D. of 1.8%. Direct analysis in closed (transparent)
      bottles was possible but more complex, requiring the superimposition of two
      sequential laser sparks. Using a surface procedure, common commercial isotonic
      products (including injectable, bacteriostatic injectable, and nasal solutions)
      were analysed. Their sodium content (corresponding to 0.9% sodium chloride) was
      accurately determined in all cases, demonstrating the capabilities of LIBS for
      the rapid analysis of liquid pharmaceutical products.

PMID- 15496321
TI  - Validation of the COSTIM bioassay for dendritic cell potency.
AB  - Dendritic cells (DCs) are increasingly prepared in vitro for use in clinical
      trials of human disease. Their utility in experimental immunotherapy has driven
      significant advances in the manufacture of these cells. Thus it has become
      imperative that, in concert with other quality control measures, a potency test
      be utilized for the GMP/GLP lot-release of DC products for preclinical and
      clinical studies. For this purpose we developed a novel method named the 'COSTIM
      bioassay', which selectively measures co-stimulatory activity, or functional
      potency of the DCs. In this method, T-cells stimulated with a sub-optimal amount
      of anti-CD3 antibody are unable to proliferate unless a source of co-stimulation
      (DCs) is added to the culture. We describe our validation of this method in this
      paper.

PMID- 15496322
TI  - Microcalorimetric evaluation of the in vitro compatibility of
      amoxicillin/clavulanic acid and ampicillin/sulbactam with ciprofloxacin.
AB  - Solution calorimetric technique has been used to determine the compatibility of
      binary and ternary systems of ampicillin trihydrate (AMP), sulbactam sodium (SS),
      amoxicillin trihydrate (AM), potassium clavulanate (PC) and ciprofloxacin
      hydrochloride (CP). The enthalpy of solution (DeltasolH) were obtained over a
      wide range of composition in the pH range 2-9. For all the pure drugs the
      DeltasolH is endothermic in nature. The molar enthalpies of interaction of binary
      (DeltaHbi.E) and ternary (DeltaHter.E) mixtures of the drugs in aqueous buffers
      have been determined. The DeltaHbi.E for all binary systems is negative and pH
      dependent (maximum pH 6-8) indicating the interaction among charged species of
      the drugs. In case of binary systems with CP the magnitude of DeltaHbi.E indicate
      strong interactions. The variation and magnitude of DeltaHbi.E for the systems is
      discussed in terms of hydrogen bonding and van der Waal's interaction in the
      solution. The interaction parameter for ternary systems (A) is positive
      indicating repulsive interaction among the drugs. The coefficients hi's
      calculated from Redlich-Kister equation for binary systems (DeltaHbi.E) and
      ternary interaction parameter (A) were used to predict the compatibility of the
      marketed formulations in pH range studied.

PMID- 15496323
TI  - An HPLC method to evaluate purity of a steroidal drug, loteprednol etabonate.
AB  - Validation of an analytical method for impurities and degradation products in an
      active pharmaceutical ingredient is important to assessment of quality and safety
      in a new pharmaceutical product. In the present study, a high-performance liquid
      chromatographic method was validated to evaluate purity of loteprednol etabonate
      (LE). LE and its four related substances, major process impurities and
      degradation products (PJ-90, PJ-91, LE-11-keto and LE-methyl ester) were well
      resolved using a phenyl-stationary phase under isocratic conditions. Two photo
      degradation products were identified as chloromethyl 17alpha-ethoxycarbonyloxy
      11beta-hydroxy-5alpha-methyl-2-oxo-19-norandrosta-1(10),3-diene-17beta
      carboxylate and chloromethyl 17alpha-ethoxycarbonyloxy-11beta-hydroxy-1-methyl-3
      oxo-6(5-->10alpha)-abeo-19-norandrosta-1,4-diene-17beta-carboxylate. A photo
      degradation product, chloromethyl 1beta,11beta-epoxy-17alpha-ethoxycarbonyloxy-2
      oxo-10alpha-androsta-4-ene-17beta-carboxylate, was not abundant by ultraviolet
      detector. The risk depending on only ultraviolet detection should be noted.
      Calibration curves for PJ-90, PJ-91, LE-11-keto and LE-methyl ester showed
      linearity over the range of 0.05-2.0% levels in LE with correlation coefficient
      of 0.999. Accuracy (n = 3) at the concentration of 0.5% level in LE for PJ-90, PJ
      91, LE-11-keto and LE-methyl ester were 2.0, 2.0, 2.3 and 2.0%, respectively.
      Intra-day repeatability (n = 6) at the concentration of 0.5% level in LE for PJ
      90, PJ-91, LE-11-keto and LE-methyl ester were 1.4, 1.4, 1.8 and 1.4%,
      respectively. The lower limits of detection for PJ-90, PJ-91, LE-11-keto and LE
      methyl ester were 0.002, 0.001, 0.004 and 0.003% levels in LE, respectively.

PMID- 15496324
TI  - Identification and quantification method of spiramycin and tylosin in
      feedingstuffs with HPLC-UV/DAD at 1 ppm level.
AB  - The use of the two macrolides antibiotics Spiramycin (S) and Tylosin (T) as
      growth promoters in animal feeding has been recently withdrawn in the European
      Union due to a concern about the outbreaks of farmacoresistance fenomena as a
      possible hazard for humans. For feed additives monitoring purposes, an analytical
      method has been developed for their extraction, purification and identification
      in different animal feedingstuffs (pelleted beef, pig, poultry feeds and calves
      milk replacer) at a minimum performance required limit (MRPL) of 1 microg g(-1)
      (ppm). Such limit has been established according to the lowest dosage of
      additives still able to elicit an appreciable growth promoting effect. Blank
      feeds were spiked at two concentration levels, 1.0 and 2.5 ppm in six replicates.
      After methanolic extraction, samples were cleaned up on SPE CN columns and
      extracts analysed in HPLC-UV/DAD, using a gradient elution. Detection limits,
      calculated as the tree time mean noise of 20 blank feeds, were 176 and 118 ng g(
      1) for S and T, respectively. Results show good repeatability (CV% not exceeding
      the value of 15) and mean recovery in the range of 99-74% and 81-53% for S and T,
      respectively, at 1 ppm. When the standards were injected up to 250 ng the
      chromatographic method can resolve the components of analytes (Spiramycin I, II
      and III; Tylosin A and B) but can not resolve the components on real feed samples
      at the spiked levels considered. For this reason the identification and
      quantification of analytes on matrix were carried out considering the main
      compound of the drugs (Spiramycin I and Tylosin A). As a verification, the
      overlapping of UV spectra in the range 220-350 nm between analytical standards
      and the compounds in the matrix were considered.

PMID- 15496325
TI  - Combined effect of pH and polysorbates with cyclodextrins on solubilization of
      naringenin.
AB  - pH control and inclusion complex formation are commonly used as solubilization
      techniques in formulating ionizable drugs. Naringenin is a weakly acid compound
      with a low water solubility. The role of both ionized and unionized species of
      naringenin in solution by complexation with beta-cyclodextrin, 2-hydroxypropyl
      beta-cyclodextrin and methyl-beta-cyclodextrin was investigated. This combined
      use of ionization and complexation increases not only the solubility of the
      unionized naringenin, but also that of the ionized one. This study puts on
      evidence the role of pH, pKa and complexation constants in increasing drug total
      aqueous solubility, determined by the single components in solution, as ionized
      and unionized naringenin both in free and complexed forms. Moreover, the presence
      of non-ionic surfactants in the media of complexation gives a positive
      contribution to the improvement of the solubility of naringenin, alone or in
      combination with beta-cyclodextrin.

PMID- 15496326
TI  - Use of in situ FT-Raman spectroscopy to study the kinetics of the transformation
      of carbamazepine polymorphs.
AB  - The solid-state transformation of carbamazepine from form III to form I was
      examined by Fourier Transform Raman spectroscopy. Using a novel environmental
      chamber, the isothermal conversion was monitored in situ at 130 degrees C, 138
      degrees C, 140 degrees C and 150 degrees C. The rate of transformation was
      monitored by taking the relative intensities of peaks arising from two CH bending
      modes; this approach minimised errors due to thermal artefacts and variations in
      power intensities or scattering efficiencies from the samples in which crystal
      habit changed from a characteristic prism morphology (form III) to whiskers (form
      I). The solid-state transformation at the different temperatures was fitted to
      various solid-state kinetic models of which four gave good fits, thus indicating
      the complexity of the process which is known to occur via a solid-gas-solid
      mechanism. Arrhenius plots from the kinetic models yielded activation energies
      from 344 kJ mol(-1) to 368 kJ mol(-1) for the transformation. The study
      demonstrates the value of a rapid in situ analysis of drug polymorphic type which
      can be of value for at-line in-process control.

PMID- 15496327
TI  - Determination of cetirizine dihydrochloride, related impurities and preservatives
      in oral solution and tablet dosage forms using HPLC.
AB  - An HPLC method was developed and validated for the determination of cetirizine
      dihydrochloride (CZ) as well as its related impurities in commercial oral
      solution and tablet formulations. Furthermore, two preservatives associated with
      the drug formulations, namely, propyl (PP) and butylparabens (BP) were
      successfully determined by this method. The chromatographic system used was
      equipped with a Hypersil BDS C18, 5 microm column (4.6 x 250 mm) and a detector
      set at 230 nm in conjunction with a mobile phase of 0.05 M dihydrogen
      phosphate:acetonitrile:methanol:tetrahydrofuran (12:5:2:1, v/v/v/v) at a pH of
      5.5 and a flow rate of 1 ml min(-1). The calibration curves were linear within
      the target concentration ranges studied, namely, 2 x 10(2) - 8 x 10(2) microg ml(
      1) and 1-4 microg ml(-1) for CZ, 20-100 microg ml(-1) for preservatives and 1-4
      microg ml(-1) for CZ related impurities. The limits of detection (LOD) and
      quantitation (LOQ) for CZ were, respectively, 0.10 and 0.34 microg ml(-1) and for
      CZ related impurities were in the ranges of 0.08-0.26 microg ml(-1) and 0.28-0.86
      microg ml(-1), respectively. The method proved to be specific, stability
      indicating, accurate, precise, robust and could be used as an alternative to the
      European pharmacopoeial method set for CZ and its related impurities.

PMID- 15496328
TI  - A rapid HPLC-DAD method for the analysis of fluoxetine and norfluoxetine in
      plasma from overdose patients.
AB  - There is a need for fast, simple and reliable analytical methods for the analysis
      of fluoxetine and norfluoxetine in patients who voluntarily or involuntarily have
      taken an overdose of the drug. A new liquid chromatographic method with diode
      array detection is presented herein for the determination of fluoxetine and its
      main active metabolite in human plasma for toxicological purposes. A mobile phase
      composed of acetonitrile and aqueous tetramethylammonium perchlorate allows to
      obtain the complete separation of the analytes on a C18 reversed phase column.
      The fast and accurate sample pre-treatment step is carried out by means of solid
      phase extraction using hydrophilic-lipophilic balance cartridges and loading 100
      microL of plasma only. This procedure gives satisfactory extraction yield values,
      as well as good plasma sample purification from matrix interference. Linearity
      was obtained in the 150-3000 ng/mL range for both analytes. Selectivity with
      respect to other psychotropic drugs was satisfactory. The method seems to be
      suitable for the analysis of fluoxetine and its metabolite in human plasma for
      depressed patients in overdose.

PMID- 15496329
TI  - Micellar liquid chromatography determination of some biogenic amines with
      electrochemical detection.
AB  - A simple and reliable liquid chromatographic procedure is successfully applied to
      the simultaneous determination of the biogenic amines, dopamine, serotonin, their
      metabolites (homovalinic acid (HVA) and hydroxyindoleacetic acid (HIAA)) as well
      as tyramine in serum samples. After an optimization procedure using a C18 column,
      the mobile phase selected was 0.15 M sodium dodecyl sulfate buffered at pH 3, in
      which the serum samples were directly injected and the analysis time for the five
      substances was less than 12 min. The use of electrochemical (ED) and ultraviolet
      (UV) detection was compared. The limits of detection of the biogenic amines
      studied were drastically improved using ED detection. Repeatability and
      intermediate precision were tested at three different concentrations and the
      relative standard deviations were below 1.5% for most assays. Finally, the method
      was successfully applied to the determination of biogenic amines in serum
      samples.

PMID- 15496330
TI  - Determination of icariin and metabolites in rat serum by capillary zone
      electrophoresis: rat pharmacokinetic studies after administration of icariin.
AB  - A simple and rapid method for determination of icariin (ICA) and its two
      metabolites, icaritin (ICT) and desmethylicaritin (DICT), by capillary zone
      electrophoresis has been developed and validated. Optimum separation of ICA, ICT,
      and DICT was obtained on 43.6 cm x 50 microm capillary using sodium tetraborate
      (30 mmol/L), monobasic sodium phosphate (50 mmol/L)-acetonitrile (50:50, v/v) (pH
      10.0) as running buffer. Carbamazepine (CMP) was used as internal standard (IS).
      The temperature and voltage were optimized at 25 degrees C and 12 kV,
      respectively. The limit of detection of ICA was 1.0 mg/L (S/N = 3) by UV
      detection at 270 nm. The elaborated method was tested in vivo after
      administration of a single dose of 120 mg ICA/kg to healthy rats. Calculated
      parameters confirmed usefulness of the method in rat pharmacokinetic studies on
      ICA.

PMID- 15496331
TI  - HPLC-UV method for assaying 99/357, a synthetic trioxane antimalarial derivative
      in rat and rabbit serum.
AB  - In the present study an accurate and precise HPLC-UV assay method in rat and
      rabbit serum has been developed and validated for determination of 99/357--a new
      synthetic analogue of artemisinin developed by Central Drug Research Institute
      (CDRI), of the class of trioxane derivative. Separation was achieved using a C-18
      reversed phase column with a mobile phase comprising of acetonitrile and
      deionized water (80:20%, v/v) using a UV detector, set at a wavelength of 266 nm.
      The method, applicable to 200 microl serum, involved double extraction of the
      samples with 20% isopropyl alcohol (IPA) in n-hexane. The recovery of 99/357 in
      the two matrices was >90%. The method was sensitive with a limit of quantitation
      of 25 ng/ml in both rat and rabbit matrices. Precision and accuracy were within
      the acceptable limits, as indicated by relative standard deviation (accuracy)
      varying from -12.7 to 5.7% and bias (precision) values ranging from 0.6 to 11.8%.
      Moreover, 99/357 was stable in serum up to 30 days of storage at -60 degrees C
      and after being subjected to three freeze/thaw cycles. The method will be applied
      to perform pharmacokinetic studies of 99/357.

PMID- 15496332
TI  - Rapid determination of minoxidil in human plasma using ion-pair HPLC.
AB  - A rapid, simple and sensitive ion-pair high-performance liquid chromatography
      (HPLC) method has been developed for quantification of minoxidil in plasma. The
      assay enables the measurement of minoxidil for therapeutic drug monitoring with a
      minimum detectable limit of 0.5 ng ml(-1). The method involves simple, one-step
      extraction procedure and analytical recovery was complete. The separation was
      performed on an analytical 150 x 4.6 mm i.d. microbondapak C18 column. The
      wavelength was set at 281 nm. The mobile phase was a mixture of 0.01 M sodium
      dihydrogen phosphate buffer and acetonitrile (60:40, v/v) containing 2.5 mM
      sodium dodecyl sulphate adjusted to pH 3.5 at a flow rate of 1 ml/min. The column
      temperature was set at 50 degrees C. The calibration curve was linear over the
      concentration range 2-100 ng ml(-1). The coefficients of variation for inter-day
      and intra-day assay were found to be less than 8%.

PMID- 15496333
TI  - Solid-phase microextraction-gas chromatography-mass spectrometric analysis of
      volatile compounds in a compounded Chinese medicinal prescription, Xiao-Cheng-Qi
      Tang.
AB  - In this paper, a headspace solid-phase microextraction (HS-SPME) coupled to gas
      chromatography-mass spectrometry (GC-MS) was applied for the analysis of volatile
      compounds in a famous compounded Chinese medicinal prescription, Xiao-Cheng-Qi
      Tang. Some parameters affecting the extraction efficiency such as stirring,
      extraction temperature, fiber exposure time and desorption time were optimized.
      The best results were obtained using a 100 microm PDMS fiber during headspace
      extraction at 90 degrees C with stirring at 1000 rpm for 20 min. Twenty-seven
      compounds were identified in Xiao-Cheng-Qi-Tang including some main compounds
      such as d-limonene and linalool. Inter- and intra-day relative standard
      deviations (R.S.Ds.) were less than 15.6%, showing that the method had a good
      reproducibility. The result might provide some foundation for building the
      convincing theory on the pharmacological activity of this prescription.

PMID- 15496334
TI  - Quantification intracellular levels of oligodeoxynucleotide-doxorubicin conjugate
      in human carcinoma cells in situ.
AB  - Bifunctional oligodeoxynucleotide-intercalator conjugates provide new tools for a
      selective control of gene expression and may have potential applications as novel
      therapeutic agents. An 'in situ' analysis method has been developed to determine
      intracellular levels of oligodeoxynucleotide- doxorubicin conjugate which may be
      used to reverse the multidrug resistance in KB-A-1 cells. A linear response over
      a broad concentration range (0.05-6.0 microM, r2 = 0.97) was obtained. The limit
      of detection and quantitation was set at 0.015 and 0.05 microM, respectively.
      Assay validation studies revealed that compared with HPLC, the method is rapid,
      high simple, high throughput and convenient for the determination of the
      conjugate in cells in situ. The uptake studies of the conjugate in cells using
      this method demonstrated that the cellular accumulation of the conjugate in KB-A
      1 cells was dependent on a dynamic balance between influx and efflux processes.

PMID- 15496335
TI  - Comparison between sodium dodecylsulphate and cetyltrimethylammonium bromide as
      mobile phases in the micellar liquid chromatography determination of non
      steroidal anti-inflammatory drugs in pharmaceuticals.
AB  - The retention behaviour of non-steroidal anti-inflammatory drugs (NSAIDs) using
      micellar mobile phases of sodium dodecylsulphate (SDS) is studied and compared
      with that observed with micellar mobile phases of cetyltrimethylammonium bromide
      (CTAB). A liquid chromatographic procedure for the determination of acemetacin,
      diclofenac, indomethacin, ketoprofen, naproxen and tolmetin in pharmaceutical
      preparations is described. The proposed system uses a Kromasil C18 analytical
      column and a solution of 0.15 M SDS at pH 3 with 10% 1-propanol as mobile phase.
      Under these conditions, the studied NSAIDs elute between 6 and 10 min at a 1 mL
      min(-1) flow rate. Limits of detection (LOD) are lower than 0.5 microg mL(-1).
      Recoveries in the analysis of the pharmaceutical preparations are ranged between
      91 and 104% respect to the nominal content declared by the manufacturers and the
      relative standard deviations are in general lower than 4%.

PMID- 15496336
TI  - Validation of a generic analytical procedure for determination of residual
      solvents in drug substances.
AB  - A generic analytical procedure for determination of residual solvents in drug
      substances is described and validated. The procedure is based on methods
      described in the European and United States parmacopeias, but is faster than the
      compendial procedures. It is applicable both during drug development and for
      quality control in commercial manufacture. The method is accurate, linear and
      shows a satisfactory level of precision. The solvents included in the validation
      comprise the five class 1 solvents, 17 out of 27 class 2 solvents, 17 out of 27
      class 3 solvents and three unclassified solvents according to ICH guideline Q3C.
      The solvents can be detected and quantified at levels at or below the ppm limits
      given in the guideline. In most cases the quantification limit is in the lower
      ppm range. A strategy is proposed to choose between water or N,N-dimethyl
      formamide as a diluent. The need for re-validation of the method, mandatory for
      quantitative procedures according to the European Pharmacopeia, is minimised when
      using the generic procedure.

PMID- 15496337
TI  - 19F NMR spectroscopic study on the binding of triflupromazine to bovine and human
      serum albumins.
AB  - The 19F NMR spectrum of triflupromazine hydrochloride (TFZ) in a buffer solution
      (pH 6.8) showed a single sharp signal of the TFZ CF3 group at 13.5 ppm from the
      external trifluoroacetic acid. The addition of 1 mM HSA or BSA to the sample
      solution caused a split of the CF3 signal into two broadened signals shifted to
      slightly lower (0.2 ppm) and higher (0.7 ppm) fields, respectively, from the
      original position. Denaturation of the albumins by guanidine hydrochloride (3M)
      restored the two broadened signals to a slightly broadened single signal,
      indicating that TFZ has at least two binding sites on HSA and BSA, respectively.
      From the competitive binding 19F NMR experiments using Warfarin (Site-I ligand),
      l-tryptophan (Site-II ligand), NaCl, and oleate, the signal at high field was
      assigned to the TFZ bound to Site II. Comparison of the signal intensity revealed
      that the affinity of TFZ for Site II on HSA was considerably higher than that on
      BSA. The low-field signal could be identified as a weight-averaged signal between
      nonspecifically bound TFZ to HSA (BSA) and free TFZ in the water phase. In the
      presence of physiological concentrations of NaCl, major binding of TFZ to HSA and
      BSA was considered to be nonspecific. The present work indicates that 19F NMR is
      very useful for obtaining important detailed information regarding the binding of
      fluorinated drugs to serum albumins.

PMID- 15496338
TI  - A method for fast determination of psoralens in oral solutions of phytomedicines
      using liquid chromatography.
AB  - A method for sample preparation and analysis by high performance liquid
      chromatography with UV detection (HPLC-UV) has been developed for routine
      analysis of psoralen and bergapten, photosensitizing compounds, in oral solutions
      of phytomedicines employed in Brazil for some illnesses. The linearity, accuracy,
      the inter- and intra-day precision of the procedure were evaluated. Calibration
      curves for psoralen and bergapten were linear in the range of 1.0-600.0 microg
      ml(-1) and 1.0-400.0 microg ml(-1) respectively. The recoveries of the psoralens
      in the oral solutions analysed were 94.43-99.97%. The percentage coefficient of
      variation (CV) of the quantitative analysis of the psoralens in the products
      analysis was within 5%. In inter-equipment study was employed gas chromatography
      flame ionization (CG-FID) detection.

PMID- 15496339
TI  - LC-MS determination and bioavailability study of loperamide hydrochloride after
      oral administration of loperamide capsule in human volunteers.
AB  - The purpose of the present study was to develop a standard protocol for
      loperamide hydrochloride bioequivalence testing. For this purpose, a simple rapid
      and selective LC-MS method utilizing a single quadrupole mass spectrometer was
      developed and validated for the determination of loperamide hydrochloride in
      human plasma, and we followed this with a bioavailability study. Methyl tert
      butylether (MTBE) was used to extract loperamide hydrochloride and ketoconazole
      (internal standard (IS)) from an alkaline plasma sample. LC separation was
      performed on a Zorbax RX C18 column (5 microm, 2.1 mm x 150 mm) using
      acetonitrile-water-formic acid (50:50:0.1 (v/v)) as a mobile phase. The retention
      times of loperamide hydrochloride and IS were 1.2 and 0.8 min, respectively.
      Quadrupole MS detection was by monitoring at m/z 477 (M + 1) corresponding to
      loperamide hydrochloride and at m/z 531 (M + 1) for IS. The described assay
      method showed acceptable precision, accuracy, linearity, stability, and
      specificity. The bioavailability of loperamide hydrochloride was evaluated in
      eight healthy male volunteers. The following pharmacokinetic parameters were
      elucidated after administering a single dose of four 2mg capsules of loperamide:
      the area under the plasma concentration versus time curve from time 0 to 72 h
      (AUC72 h) 19.26 +/- 7.79 ng h/ml; peak plasma concentration (Cmax) 1.18 +/- 0.37
      ng/ml; time to Cmax (Tmax) 5.38 +/- 0.74 h; and elimination half-life (t1/2)
      11.35 +/- 2.06 h. The developed method was successfully used to study the
      bioavailability of a low dose (8 mg) of loperamide hydrochloride.

PMID- 15496340
TI  - Gender, work-home conflict, and morbidity amongst white-collar bank employees in
      the United Kingdom.
AB  - Most research on work-home conflict focuses solely on women. This study compares
      men and women's perceptions of the extent to which paid work interferes with
      family life, and examines associations between work-home conflict and health.
      Data were collected from 2,176 full-time white-collar employees of a British
      bank. We did not find any significant gender differences in perceptions of work
      home conflict. However, predictors of work-home conflict did vary by gender;
      having children and being in a senior position were more strongly related to work
      home conflict for women than for men, while working unsociable hours was more
      important for men than for women. Work-home conflict was strongly associated with
      reporting fair or poor self-assessed health, a high number of reported physical
      symptoms and minor psychological morbidity (GHQ-12). These associations were
      equally strong for men and women. Our results suggest that work-home conflict is
      a problem for men as well as women.

PMID- 15496341
TI  - Perceived environment and physical activity in youth.
AB  - The examination of physical environments to explain and promote physical activity
      is an important yet under-investigated area of research inquiry. This study
      explored relationships between the perceived availability of physical
      environmental resources and the perceived importance of these resources in
      relation to physical activity levels amongst youth. A self-report questionnaire
      was completed by 610 students (mean age = 15.5 years old; 62% female
      participants) from four high schools (grades 9-12) in rural Alberta, Canada.
      Perceived physical environment constructs explained 5% of the variance in
      physical activity, with home, neighborhood, and school as significant domains.
      Perceived importance constructs explained 8% of the variance in physical activity
      with school context showing the only significant relationship with physical
      activity. A hierarchical regression analysis entered sex, grade, self-efficacy,
      peer, family and physical education teacher relationships, as the first block and
      eight environmental constructs as the second block. The first block variables
      accounted for 22% of the variance and environmental constructs accounted for an
      added 4% of the variance in physical activity. Perceived importance of the school
      environment was the only environment variable significantly associated with
      physical activity (beta = .14; p < .05) after taking into account the impact of
      these traditional predictors. These findings reinforce the need to provide and
      support school physical environments related to physical activity.

PMID- 15496342
TI  - Explaining the social gradient in health in Canada: using the National Population
      Health Survey to examine the role of stressors.
AB  - Understanding the mechanisms that explain the pervasive association between
      socioeconomic status and health has been identified as an important area of
      research. Using the 1994-1995 National Population Health Survey, this study
      examines whether exposure to psychosocial stressors may be one mediating
      mechanism of the social gradient in health. Data were obtained including
      indicators of socioeconomic status (SES); exposure to recent life events and
      chronic stressors; and self-rated health status. Results showed a clear gradient
      in poor self-rated health with decreasing SES. Higher exposure to stressors
      across several domains was also observed with decreasing SES. Exposure to
      stressors was further associated with poor self-rated health, above and beyond
      adjusting for SES. Across income adequacy groups, exposure to stressors accounted
      for 16% to 26% of the relationship between income group and poor self-rated
      health among men and for 6% to 15% among women, suggesting that exposure to
      psychosocial stressors may be one of the mediators underlying the higher
      prevalence of poor self-rated health within lower socioeconomic groups.

PMID- 15496343
TI  - Couch kids: correlates of television viewing among youth.
AB  - The purpose of this study was to review the published empirical correlates of
      television/video viewing among youth (2 to 18 years). A descriptive semi
      quantitative review was conducted based on 68 primary studies. Variables
      consistently associated with TV/video viewing were ethnicity (non-white +),
      parent income (-), parent education (-), body weight (+), between meal snacking
      (+), number of parents in the house (-), parents TV viewing habits (+), weekend
      (+) and having a TV in the bedroom (+). Variables consistently unrelated to
      TV/video viewing were sex, other indicators of socio-economic status, body
      fatness, cholesterol levels, aerobic fitness, strength, other indicators of
      fitness, self-perceptions, emotional support, physical activity, other diet
      variables, and being an only child. Few modifiable correlates have been
      identified. Further research should aim to identify modifiable correlates of
      TV/video viewing if interventions are to be successfully tailored to reduce this
      aspect of inactivity among youth.

PMID- 15496344
TI  - Prophecies of childhood: how children's social environments and biological
      propensities affect the health of populations.
AB  - During the past decade, important steps have been taken globally to improve the
      status of children. Concurrently, significant advances have been made toward
      understanding how child development is shaped by transactions between biological
      and environmental influences. Despite such advances, ongoing adversities in the
      lives of children worldwide undermine the development of individuals and thus the
      health of nations. The primary tenets of this paper are that: children continue
      to suffer a disproportionate share of the world's adversities; exposure to early
      adversities is not only associated with increased morbidity during childhood, but
      also across the lifespan; and recent advances in understanding the operation and
      ontogeny of stress-response systems can help explain how adversity is translated
      into lifelong effects on health. Acknowledging the long-lasting sequelae of
      childhood adversity has important implications for public health and society.

PMID- 15496345
TI  - Preliminary study: psychological effects of muscle relaxation on juvenile
      delinquents.
AB  - The purpose of this study is to test our hypothesis that muscle relaxation is
      effective on the psychological well-being of juvenile delinquents. Subjects were
      16 juvenile delinquents who had entered a reform school. Subjects were divided
      into two groups. The muscle relaxation group received muscle relaxation therapy
      once a week for a total of 4 times. The control group spent an ordinary daily
      life in the reformatory. Psychological questionnaires used were the Rosenzweig
      Picture Frustration Study (P-F study), the Psychological Stress Response Scale
      (PSRS), and the Eysenck Personality Questionnaire (EPQ). There was a significant
      Group Time interaction of the Group Conformity Rating (GCR) of the P-F study (F
      [1,14] =10.1, P=0.007). There were no significant interactions in the other
      psychological subscales. Thus, muscle relaxation therapy may improve frustration
      tolerance among juvenile delinquents.

PMID- 15496347
TI  - Advances in early-stage breast cancer treatment. It's October, and once again,
      we're observing Breast Cancer Awareness month. Here's a progress report.

PMID- 15496346
TI  - Ethnic differences in cardiovascular responses to laboratory stress: a comparison
      between asian and white americans.
AB  - Compared to other ethnic groups, Asian Americans show significantly lower rates
      of cardiovascular disease (CVD). We tested the hypothesis that Asian Americans
      would show reduced cardiovascular responses to laboratory stressors than
      Caucasians. Forty-three Asians (18 men, 25 women) and 77 Caucasians (36 men, 41
      women) with a mean age of 24 years (SD = 3.93) participated in a stress
      reactivity protocol consisting of four tasks (speech, serial subtraction, mirror
      tracing, handgrip) while heart rate (HR), systolic blood pressure (SBP), and
      diastolic blood pressure (DBP) were measured. Asian Americans demonstrated
      overall lower reactivity across tasks for SBP F(1,117 = 7.48, p < .01) and a
      trend toward lower HR response F(1,117 = 3.18, p < .10). A significant ethnicity
      by task interaction was observed for HR reactivity F(3,351 = 2.94, p < .05) such
      that Caucasians showed greater responses for the subtraction task.

PMID- 15496348
TI  - Psychotherapy at midlife: worth the trouble.

PMID- 15496349
TI  - MRI a valuable add-on to mammography for some women.

PMID- 15496350
TI  - Time for tea. A growing number of studies suggest that drinking tea, especially
      green tea, is good for you.

PMID- 15496351
TI  - By the way, doctor. I've been diagnosed with deQuervain's tenosynovitis. What can
      I do to help it heal?

PMID- 15496352
TI  - By the way, doctor. Three years ago I had a deep vein thrombosis. Should I now
      avoid any treatment for spider or varicose veins?

PMID- 15496353
TI  - Is obesity a mental health issue?

PMID- 15496354
TI  - Drug treatment of schizophrenia: what experts are recommending.

PMID- 15496355
TI  - Questions & answers. What is the relationship between stroke and depression. Does
      depression increase the risk of stroke? How does depression affect life
      expectancy after a stroke?

PMID- 15496356
TI  - Depression--theme and variations.

PMID- 15496357
TI  - Whole grains: why the fuss?

PMID- 15496359
TI  - Exhaustion and the heart.

PMID- 15496358
TI  - Body fat and health: less is more.

PMID- 15496360
TI  - On call. Nearly every day I seem to get an e-mail offering a foolproof way to
      lengthen my penis. Is there anything to this?

PMID- 15496361
TI  - On call. I am 47 years old and I've just been diagnosed with high blood pressure.
      My doctor wants to put me on medication, but I'm worried that it will make me
      impotent. If I decide to take a drug, which would be best?

PMID- 15496362
TI  - New lowdown on cholesterol. The latest advisory ratchets down targets for LDL
      (bad) cholesterol for some people, not others; no one-size-fits-all
      recommendations yet.

PMID- 15496363
TI  - Take pressure off your sex life. High blood pressure can contribute to sexual
      problems, as can some treatments for it.

PMID- 15496364
TI  - Positive winds of change for pulmonary hypertension. New treatments offer help
      and hope for people with high blood pressure in the lungs.

PMID- 15496365
TI  - Chest pain isn't all bad.

PMID- 15496366
TI  - Brain bonus with niacin?

PMID- 15496367
TI  - Blood pressure drugs may fight cancer, too.

PMID- 15496368
TI  - Inherited fibrillation.

PMID- 15496369
TI  - Beta blockers and heart failure.

PMID- 15496370
TI  - Ask the doctor. I need to quit drinking, but don't think I can do it on my own.
      Can I use a drug like Antabuse even though I have heart disease?

PMID- 15496371
TI  - Ask the doctor. Every day I take a baby aspirin (81 milligrams) that is coated to
      protect my stomach. Out of curiosity, I dropped a tablet into a glass filled with
      equal parts water and vinegar. Two days later, it hadn't dissolved. That has me
      wondering if the aspirin inside the coating gets into my stomach and bloodstream,
      or whether I've been unprotected against heart disease all this time?

PMID- 15496372
TI  - A lifetime of distractions. ADHD is no longer just a children's disease. Many
      adults are being diagnosed and treated for the condition.

PMID- 15496373
TI  - Staying the course. Getting the right medication is only half the battle.

PMID- 15496374
TI  - Essential tremor. Parkinson's disease isn't the only disease that causes shaky
      hands. Essential tremor may be less well known, but it's far more common.

PMID- 15496375
TI  - Vitamins after angioplasty: maybe not such a good idea after all.

PMID- 15496376
TI  - Quitting smoking: sooner is best, but later is better than not at all.

PMID- 15496377
TI  - School spirits.

PMID- 15496378
TI  - By the way, doctor. I have been taking two Advil tablets two or three times per
      day to reduce pain and inflammation in my knees. Could it be harmful to do this
      for an extended period of time, say a year?

PMID- 15496379
TI  - By the way, doctor. I have phlebotomies every six months to manage my
      hemochromatosis. At my most recent bloodletting, a fibrous clot came out after
      the nurse removed the needle from my forearm. It seems to me that such clotting
      presents an unnecessary risk for ischemic stroke. What do you think?

PMID- 15496381
TI  - Production of Yersinia stable toxin (YST) and distribution of yst genes in
      biotype 1A strains of Yersinia enterocolitica.
AB  - Two hundred and fifty nine isolates of Yersinia enterocolitica and related
      species were examined for the production of heat-stable enterotoxin (Yersinia
      stable toxin; YST) as well as for the prevalence of enterotoxin genes, viz. ystA,
      ystB and ystC. Under the conventional conditions used for the production of Y.
      enterocolitica enterotoxin, i.e. in tryptic soy broth (TSB) supplemented with
      yeast extract at 28 degrees C for 48 h, 77.7 % of clinical isolates and 62.3 % of
      swine isolates showed enterotoxigenicity in infant mice. All isolates that
      produced enterotoxin at 28 degrees C also showed enterotoxic activity at 37
      degrees C after 48 h incubation under an alkaline pH of 7.5, the pH present in
      the ileum. All Yersinia intermedia and Yersinia frederiksenii isolates were
      negative for enterotoxin production. All clinical isolates and 96.3 % of Y.
      enterocolitica isolates from swine hybridized with a probe for ystB, which
      indicated that the ystB gene was most prevalent in Y. enterocolitica biotype 1A
      strains. None of the Y. enterocolitica isolates showed hybridization with
      oligonucleotide probes for ystA or ystC. The study indicated that YST-b was the
      major contributor to diarrhoea produced by biotype 1A strains of Y.
      enterocolitica.

PMID- 15496380
TI  - Role of quorum sensing in the pathogenicity of Burkholderia pseudomallei.
AB  - Burkholderia pseudomallei is the causative agent of human and animal melioidosis.
      The role of quorum sensing (QS) in the in vivo pathogenicity of B. pseudomallei
      via inhalational exposure of BALB/c mice and intraperitoneal challenge of Syrian
      hamsters has not been reported. This investigation demonstrates that B.
      pseudomallei encodes a minimum of three luxI and five luxR homologues that are
      involved in animal pathogenicity. Mass spectrometry analysis of culture
      supernatants revealed that wild-type B. pseudomallei and the luxI mutants
      synthesized numerous signalling molecules, including N-octanoyl-homoserine
      lactone, N-decanoyl-homoserine lactone, N-(3-hydroxyoctanoyl)-L-homoserine
      lactone, N-(3-hydroxydecanoyl)-L-homoserine lactone and N-(3-oxotetradecanoyl)-L
      homoserine lactone, which was further confirmed by heterologous expression of the
      B. pseudomallei luxI alleles in Escherichia coli. Mutagenesis of the B.
      pseudomallei QS system increased the time to death and reduced organ colonization
      of aerosolized BALB/c mice. Further, intraperitoneal challenge of Syrian hamsters
      with the B. pseudomallei QS mutants resulted in a significant increase in the
      LD50. Using semi-quantitative plate assays, preliminary analysis suggests that QS
      does not affect lipase, protease and phospholipase C biosynthesis/secretion in B.
      pseudomallei. The findings of the investigation demonstrate that B. pseudomallei
      encodes multiple luxIR genes, and disruption of the QS alleles reduces animal
      pathogenicity, but does not affect exoproduct secretion.

PMID- 15496382
TI  - Occurrence of virulence-associated genes in clinical Enterococcus faecalis
      strains isolated in Londrina, Brazil.
AB  - Epidemiological studies have reinforced the importance of Enterococcus faecalis
      in causing serious infections, and to date, our understanding of how certain
      virulence factors are involved in the pathogenesis of enterococcal infections is
      still limited. The aim of the present study was to examine the occurrence of
      known virulence determinants in a group of E. faecalis strains isolated from
      different clinical sources in Brazil. A total of 95 E. faecalis strains were
      investigated for the presence of nine virulence genes including aggA, cylA, cylB,
      cylM, eep, efaA, enlA, esp and gelE by using PCR. The data showed a relatively
      wide distribution of the virulence genes among the investigated strains. The
      clinical strains carried at least one and concomitantly up to as many as eight
      virulence markers, with two or three being the most common pattern. Most of the
      strains carried efaA (58.9 %), eep (58.9 %) and esp (57.9 %) genes, whereas the
      remaining virulence markers were detected in variable percentages ranging from
      9.5 to 45 %. Simultaneous presence of virulence markers was observed among
      clinical strains regardless of their sources. In this study, the efaA+ esp+ gelE+
      profile was the virulence genotype most frequently detected among E. faecalis
      strains. Finally, there was no significant association between virulence markers
      and clinical sources.

PMID- 15496383
TI  - Role of anti-CD3 in modulation of Th1-type immune response in Shigella
      dysenteriae infection.
AB  - A murine model was used to evaluate the role of anti-CD3 in modulating a Th1-type
      response by restimulation of T-cells after immunization with the 57 kDa
      immunodominant antigen of Shigella dysenteriae 1 outer-membrane proteins (OMPs),
      followed by Shigella infection after immunization. To observe the effect of anti
      CD3, other T-cell cultures were also established following anti-CD1, anti-IL2 and
      phytohaemagglutinin stimulation. Anti-CD3 stimulation of reconstituted T-cells
      showed 'mean' levels of CD4 and CD25 were enhanced by 34.5 and 31.1 % in
      immunized mice, which was comparable to 53.2 and 50.7 %, respectively, in
      challenged-immunized mice, and were dominant over CD8+ T-cells. Levels of IL2
      generated by anti-CD3-stimulated T-cells of immunized mice were greater than
      those of unstimulated T-cells and were significantly elevated in challenged
      immunized mice. The reactivity of T-cells indicated their complete
      responsiveness, as anti-CD3 antibody might not inhibit the migration of the
      macrophages but rather inhibit IL4. These macrophage factors synergistically act
      with anions towards an activated response, which in turn provokes IL2 secretion
      with a low degree of internalization of its receptor. Thus, sharing of IL2 to
      form a high-affinity receptor complex with CD4+ T-cells through motive signals
      suggested a generalized T-cell activation with increased humoral responses.
      Macrophage migration inhibition factor (MIF) and IL4 responses during anti-CD3
      stimulation of immunized mice indicated that the role of anti-CD3 in generation
      of O2- is due to a synergistic effect by Th1 subsets of Th0 cells. The above
      findings should have implications for understanding the immunoregulatory role of
      anti-CD3 associated with 57 kDa antigen in immunoprophylactic measures.

PMID- 15496384
TI  - Streptococcus sinensis may react with Lancefield group F antiserum.
AB  - Lancefield group F streptococci have been found almost exclusively as members of
      the 'Streptococcus milleri' group, although they have been reported very
      occasionally in some other streptococcal species. Among 302 patients with
      bacteraemia caused by viridans streptococci over a 6-year period, three cases
      were caused by Streptococcus sinensis (type strain HKU4T, HKU5 and HKU6). All
      three patients had infective endocarditis complicating their underlying chronic
      rheumatic heart diseases. Gene sequencing showed no base differences between the
      16S rRNA gene sequences of HKU5 and HKU6 and that of HKU4T. All three strains
      were Gram-positive, non-spore-forming cocci arranged in chains. All grew on sheep
      blood agar as alpha-haemolytic, grey colonies of 0.5-1 mm in diameter after 24 h
      incubation at 37 degrees C in ambient air. Lancefield grouping revealed that HKU5
      and HKU6 were Lancefield group F, but HKU4T was non-groupable with Lancefield
      groups A, B, C, D, F or G antisera. HKU4T was identified by the Vitek system
      (GPI), API system (20 STREP) and ATB system (ID32 STREP) as 99 % Streptococcus
      intermedius, 51.3 % S. intermedius and 99.9 % Streptococcus anginosus,
      respectively. Using the same tests, HKU5 was identified as 87 % Streptococcus
      sanguinis/Streptococcus gordonii, 59 % Streptococcus salivarius and 99.6 % S.
      anginosus, respectively, and HKU6 as 87 % S. sanguinis/S. gordonii, 77 %
      Streptococcus pneumoniae and 98.3 % S. anginosus, respectively. The present data
      revealed that a proportion of Lancefield group F streptococci could be S.
      sinensis. Lancefield group F streptococci should not be automatically reported as
      'S. milleri'.

PMID- 15496385
TI  - Rapid genotyping of Pseudomonas aeruginosa isolates harboured by adult and
      paediatric patients with cystic fibrosis using repetitive-element-based PCR
      assays.
AB  - In this study, the suitability of two repetitive-element-based PCR (rep-PCR)
      assays, enterobacterial repetitive intergenic consensus (ERIC)-PCR and BOX-PCR,
      to rapidly characterize Pseudomonas aeruginosa strains isolated from patients
      with cystic fibrosis (CF) was examined. ERIC-PCR utilizes paired sequence
      specific primers and BOX-PCR a single primer that target highly conserved
      repetitive elements in the P. aeruginosa genome. Using these rep-PCR assays, 163
      P. aeruginosa isolates cultured from sputa collected from 50 patients attending
      an adult CF clinic and 50 children attending a paediatric CF clinic were typed.
      The results of the rep-PCR assays were compared to the results of PFGE. All three
      assays revealed the presence of six major clonal groups shared by multiple
      patients attending either of the CF clinics, with the dominant clonal group
      infecting 38 % of all patients. This dominant clonal group was not related to the
      dominant clonal group detected in Sydney or Melbourne (pulsotype 1), nor was it
      related to the dominant groups detected in the UK. In all, PFGE and rep-PCR
      identified 58 distinct clonal groups, with only three of these shared between the
      two clinics. The results of this study showed that both ERIC-PCR and BOX-PCR are
      rapid, highly discriminatory and reproducible assays that proved to be powerful
      surveillance screening tools for the typing of clinical P. aeruginosa isolates
      recovered from patients with CF.

PMID- 15496386
TI  - Genetic relatedness of antibiotic-resistant pneumococci isolated during case
      clusters.
AB  - Multilocus sequence typing of Streptococcus pneumoniae associated with two case
      clusters of disease is reported here for the first time. Isolates from the first
      cluster were serotype 19F, resistant to penicillin and erythromycin, and were
      characterized as ST 320. Isolates from the second cluster were serogroup 4,
      resistant to ciprofloxacin, and were characterized as ST 206. Therefore, the
      isolates from these clusters were antibiotic-resistant, of serotypes infrequently
      isolated, and of uncommon sequence types.

PMID- 15496387
TI  - Erythromycin resistance in invasive serotype 14 pneumococci is highly related to
      clonal type.
AB  - Sixty-seven serotype 14 pneumococci, isolated from invasive disease in Scotland
      during the first 6 months of 2003, were characterized. Serotype 14 pneumococci
      accounted for 18.2 % of the total number of cases. Serotyping, multilocus
      sequence typing and antibiotic susceptibility testing revealed 10 different
      sequence types (STs), predominantly ST 9 and ST 124; most ST 9 pneumococci were
      erythromycin-resistant whilst those of ST 124 were not.

PMID- 15496388
TI  - Assessing clonality of Vibrio cholerae Inaba isolates by characterization of
      nonsense mutations in wbeT.
AB  - The transferase gene wbeT of six clinical isolates of Vibrio cholerae O1 biotype
      El Tor was analysed. Two unique mutations were identified in the wbeT gene of
      three Inaba isolates. Due to their random nature, mutations in wbeT can be used
      to determine the clonal origin of clinical Inaba isolates.

PMID- 15496389
TI  - Global distribution of Streptococcus pneumoniae serotypes isolated from
      paediatric patients during 1999-2000 and the in vitro efficacy of telithromycin
      and comparators.
AB  - Few data exist on the distribution of Streptococcus pneumoniae serotypes in many
      countries and in non-invasive disease overall. Here, data are presented from 772
      paediatric isolates from children with community-acquired respiratory tract
      infections isolated from the PROTEKT global surveillance study during 1999-2000.
      Overall, 60.0 % of isolates were covered by the 7-valent pneumococcal vaccine
      formulation (PCV7), with greater coverage in the USA compared with Europe (69.6
      vs 55.5 %, P = 0.014). Geographically dispersed clones of serogroups 3, 11 and 15
      accounted for most of the isolates outside PCV7 coverage. Overall, macrolide,
      penicillin and cotrimoxazole non-susceptibility rates were high; however, all
      isolates were susceptible to telithromycin. Although only 7.4 % of isolates were
      resistant to amoxycillin/clavulanate, a higher prevalence of resistance was found
      in isolates from the USA and South Korea. This study shows the feasibility and
      importance of serotyping antibiotic surveillance study isolates and the potential
      of telithromycin as an important option for empiric therapy.

PMID- 15496390
TI  - Enhanced active efflux, repression of porin synthesis and development of Mar
      phenotype by diazepam in two enterobacteria strains.
AB  - The aim of this work was to determine whether diazepam could induce the multiple
      antibiotic resistance (Mar) phenotype in Klebsiella pneumoniae and Escherichia
      coli strains. The Mar phenotype is characterized by decreased susceptibility to
      multiple antibiotics due to the loss of porins and/or increased expression of
      active efflux systems. The effect of subinhibitory concentrations of diazepam on
      the susceptibility of different antimicrobial agents, outer-membrane protein
      expression and norfloxacin intracellular accumulation was studied. The results
      revealed that diazepam concentrations equal or twice adult dosage induced the
      same Mar phenotype as two well known E. coli marRAB inducers, sodium salicylate
      and sodium benzoate. Susceptibility to norfloxacin in a K. pneumoniae clinical
      isolate and E. coli strain Ag100 decreased due to enhanced active efflux and loss
      of porin expression. A decreased susceptibility to chloramphenicol, tetracycline,
      nalidixic acid and beta-lactam antibiotics was also observed. In conclusion, like
      sodium salicylate or sodium benzoate, diazepam may induce the Mar phenotype.

PMID- 15496391
TI  - Role of the rdxA and frxA genes in oxygen-dependent metronidazole resistance of
      Helicobacter pylori.
AB  - Almost 50 % of all Helicobacter pylori isolates are resistant to metronidazole,
      which reduces the efficacy of metronidazole-containing regimens, but does not
      make them completely ineffective. This discrepancy between in vitro metronidazole
      resistance and treatment outcome may partially be explained by changes in oxygen
      pressure in the gastric environment, as metronidazole-resistant (MtzR) H. pylori
      isolates become metronidazole-susceptible (MtzS) under low oxygen conditions in
      vitro. In H. pylori the rdxA and frxA genes encode reductases which are required
      for the activation of metronidazole, and inactivation of these genes results in
      metronidazole resistance. Here the role of inactivating mutations in these genes
      on the reversibility of metronidazole resistance under low oxygen conditions is
      established. Clinical H. pylori isolates containing mutations resulting in a
      truncated RdxA and/or FrxA protein were selected and incubated under anaerobic
      conditions, and the effect of these conditions on the MICs of metronidazole,
      amoxycillin, clarithromycin and tetracycline, and cell viability were determined.
      While anaerobiosis had no effect on amoxycillin, clarithromycin and tetracycline
      resistance, all isolates lost their metronidazole resistance when cultured under
      anaerobic conditions. This loss of metronidazole resistance also occurred in the
      presence of the protein synthesis inhibitor chloramphenicol. Thus, factor(s) that
      activate metronidazole under low oxygen tension are not specifically induced by
      low oxygen conditions, but are already present under microaerophilic conditions.
      As there were no significant differences in cell viability between the clinical
      isolates, it is likely that neither the rdxA nor the frxA gene participates in
      the reversibility of metronidazole resistance.

PMID- 15496392
TI  - Comparative analysis of Clostridium difficile clinical isolates belonging to
      different genetic lineages and time periods.
AB  - Recent studies have shown that Clostridium difficile strains with variant toxins
      and those with resistance to macrolide-lincosamide-streptogramin B (MLSB) are
      increasingly causing severe disease and outbreaks in hospital settings. Here, the
      pathogenicity locus (PaLoc), the acquisition of binary toxin, and the genotypic
      and phenotypic characteristics of antibiotic resistance of 74 C. difficile
      clinical strains isolated from symptomatic patients in Italy during different
      time periods were studied. These strains were found to belong to two different
      lineages, and those isolated before 1991 were genetically unrelated to the more
      recent strains. The majority of recent C. difficile strains showed variations in
      toxin genes and in the toxin negative regulator (tcdC) and had the binary toxin.
      In 62 % of them, variations in tcdC and the presence of the binary toxin were
      associated. Five classes of susceptibility/resistance pattern (EC-a to -e) for
      erythromycin and clindamycin were identified in all strains studied. Most of the
      recent isolates belonged to EC-d and EC-e and, although erythromycin-resistant in
      vitro, did not harbour the commonly associated ermB determinant. Interestingly,
      two strains of the EC-d class were resistant to clindamycin only after induction
      with subinhibitory concentrations of the antibiotic. A decrease in tetracycline
      and chloramphenicol MIC values was also observed in the recently isolated
      strains, associated with less frequent detection of the catD and tetM genes. Two
      tetM-positive strains were resistant in vitro only after induction with
      subinhibitory concentrations of the antibiotic. The acquisition of the binary
      toxin, the possible increase in toxin production due to a mutated negative
      regulator and a decrease in the fitness cost as a result of lower levels of
      antibiotic resistance or other mechanisms may have led to the successful
      establishment of these new phenotypes, with potentially serious clinical
      implications.

PMID- 15496393
TI  - Association of atypical enteropathogenic Escherichia coli (EPEC) with prolonged
      diarrhoea.
AB  - The aim of the present case control study was to investigate the prevalence of
      atypical enteropathogenic Escherichia coli (EPEC) and its possible role in
      causing diarrhoea among children < 5 years of age in Norway. Stool specimens
      received in the laboratory from children with suspected gastroenteritis (n = 251)
      were, in addition to routine testing, analysed for the presence of EPEC by PCR of
      the eae, bfpA and stx genes. Specimens from healthy children (n = 210) recruited
      from Maternal and Child Health Centres were analysed for EPEC only. EPEC isolates
      (eae+, stx-) were classified as typical (bfpA+) or atypical (bfpA-), and were
      tested for O : K serogroup. Information on duration of diarrhoea was recorded in
      a questionnaire and from referral forms. Atypical EPEC was diagnosed in 37
      patients (14.7 %) compared to 21 (10.0 %) of the healthy controls [Odds ratio
      (OR) = 1.4, P = 0.3]. Only three isolates, all from patients, belonged to EPEC
      serogroups. One patient had typical EPEC. Twenty (22.5 %) of 89 patients with
      diarrhoea lasting > or = 14 days had atypical EPEC. The association between
      atypical EPEC and prolonged diarrhoea (OR = 2.1, P = 0.04) was caused by a high
      prevalence among female patients (40.6 %). In conclusion, atypical EPEC was found
      to be slightly more prevalent in patients than controls, without any overall
      significant association with diarrhoea. However, a significant association was
      observed with diarrhoea lasting 14 days or more, a finding that may indicate a
      role for atypical EPEC in prolonged disease.

PMID- 15496394
TI  - Distribution of espI among clinical enterohaemorrhagic and enteropathogenic
      Escherichia coli isolates.
AB  - Enterohaemorrhagic (EHEC) and enteropathogenic (EPEC) Escherichia coli are
      important diarrhoeagenic pathogens; infection is dependent on translocation of a
      number of type III effector proteins. Until recently all the known effectors were
      encoded on the LEE pathogenicity island, which also encodes the adhesin intimin
      and the type III secretion apparatus. Recently, a novel non-LEE effector protein,
      EspI/NleA, which is required for full virulence in vivo and is encoded on a
      prophage, was identified. The aim of this study was to determine the distribution
      of espI among clinical EHEC and EPEC isolates. espI was detected in 86 % and 53 %
      of LEE+ EHEC and EPEC strains, respectively. Moreover, the espI gene was more
      commonly found in patients suffering from a more severe disease.

PMID- 15496395
TI  - Predictive value of isolating Pseudomonas aeruginosa from aerobic and anaerobic
      blood culture bottles.
AB  - Pseudomonas aeruginosa is a particularly virulent pathogen when it causes
      bacteraemia and early diagnosis is essential to reduce morbidity and mortality.
      It is an aerobe and is thought by many to be almost exclusively isolated from the
      aerobic blood culture bottle in cases of bacteraemia. This study analysed 277
      Gram-negative bacteraemic episodes over 1 year at a single institution in order
      to assess the predictive value of this finding. In 39 of 44 episodes of P.
      aeruginosa bacteraemia, the organism was isolated from the aerobic bottle only,
      which gave a sensitivity of 88.6 % for this 'test' and a specificity of 73.8 %.
      However, for all episodes of Gram-negative bacteraemia, the likelihood of a Gram
      negative bacillus occurring in the aerobic bottle first being P. aeruginosa was
      only 39 %. The converse finding of a Gram-negative bacillus isolated first in the
      anaerobic bottle or from both bottles together was clinically helpful, having a
      negative predictive value of 97.2 % (i.e. that the organism was not P.
      aeruginosa).

PMID- 15496396
TI  - Infection with cytomegalovirus in patients with inflammatory bowel disease:
      prevalence, clinical significance and outcome.
AB  - Despite frequent use of immunosuppressive drugs in patients with inflammatory
      bowel disease (IBD) and reports of cytomegalovirus (CMV) infection following post
      transplant immunosuppression, data on the frequency and clinical significance of
      CMV in patients with IBD are scant. Sixty-three patients with IBD (61 ulcerative
      colitis and two Crohn's disease) were evaluated for CMV using serology (IgM
      antibody, mu-capture ELISA), PCR for CMV DNA in colonic biopsy and histological
      assessment of haematoxylin and eosin-stained colonic biopsy. Positive result in
      any test was considered as CMV infection. Various parameters associated with CMV
      infection were analysed using univariate and multivariate analysis. Ten of 63
      (15.8 %) patients (age 36.0 +/- 11.2 years, 31 female) were infected with CMV
      (DNA alone in four, IgM antibody alone in two and both in four, inclusion body in
      one). Patients with CMV infection were more often female (8/10 vs 23/53, P <
      0.05), had pancolitis (10/10 vs 33/53, P < 0.05), histological activity (9/10 vs
      17/53, P < 0.005) and used azathioprine (5/10 vs 7/53, P = 0.04; Fisher exact
      test for all). On multivariate analysis, female gender, pancolitis and
      histological activity were the independent factors associated with infection.
      Patients with CMV infection more often required surgical treatment for IBD (4/10
      vs 4/53, P = 0.01) and had fatal outcome (3/10 vs 0/53, P = 0.003). CMV infection
      in patients with IBD may be common and is associated with poor outcome. PCR of
      rectal biopsy was the most sensitive method of detection followed by IgM antibody
      for diagnosis.

PMID- 15496397
TI  - Clonal relationship of recent invasive Haemophilus influenzae serotype f isolates
      from Denmark and the United States.
AB  - Surveillance performed after the introduction of general Haemophilus influenzae
      serotype b (Hib) vaccination in Denmark identified 13 cases of invasive
      bacteraemic H. influenzae serotype f (Hif) disease in adults over a period of 7
      years. Bacteraemic respiratory tract infections accounted for 61 % of cases, but
      meningitis, epiglottitis and osteoarthritis were also seen. Recent Danish
      isolates were compared to recent American isolates, historical Hif strains and
      non-Hif invasive strains. Results of conventional serotyping were confirmed by
      PCR detection of the serotype-f-specific cap and bexA gene sequences. Multilocus
      enzyme electrophoresis typing revealed that recent Danish and American isolates
      belonged to a single Hif clone, which may be undergoing expansion. The need for
      accurate serotyping of H. influenzae to enable reliable monitoring for Hib
      replacement by other capsular types is emphasized.

PMID- 15496398
TI  - Two intriguing Bilophila wadsworthia cases from Hungary.
AB  - Bilophila wadsworthia, an obligately anaerobic Gram-negative bacillus, was first
      isolated from appendicitis specimens and human faeces. The two cases described
      here are the first report of the isolation of B. wadsworthia in Hungary, and
      include the first isolation from chronic mastoiditis complicated with a brain
      abscess.

PMID- 15496399
TI  - Contribution of culture media and chemical properties of polystyrene tissue
      culture plates to biofilm development by Staphylococcus aureus.

PMID- 15496400
TI  - Negative regulation of JNK signaling by the tumor suppressor CYLD.
AB  - CYLD is a tumor suppressor that is mutated in familial cylindromatosis, an
      autosomal dominant predisposition to multiple tumors of the skin appendages.
      Recent studies suggest that transfected CYLD has deubiquitinating enzyme activity
      and inhibits the activation of transcription factor NF-kappaB. However, the role
      of endogenous CYLD in regulating cell signaling remains poorly defined. Here we
      report a critical role for CYLD in negatively regulating the c-Jun NH(2)-terminal
      kinase (JNK). CYLD knockdown by RNA interference results in hyper-activation of
      JNK by diverse immune stimuli, including tumor necrosis factor-alpha, interleukin
      1, lipopolysaccharide, and an agonistic anti-CD40 antibody. The JNK-inhibitory
      function of CYLD appears to be specific for immune receptors because the CYLD
      knockdown has no significant effect on stress-induced JNK activation.
      Consistently, CYLD negatively regulates the activation of MKK7, an upstream
      kinase known to mediate JNK activation by immune stimuli. We further demonstrate
      that CYLD also negatively regulates IkappaB kinase, although this function of
      CYLD is seen in a receptor-dependent manner. These findings identify the JNK
      signaling pathway as a major downstream target of CYLD and suggest a receptor
      dependent role of CYLD in regulating the IkappaB kinase pathway.

PMID- 15496401
TI  - Tetrameric oligomerization mediates transcriptional repression by the BRCA1
      dependent Kruppel-associated box-zinc finger protein ZBRK1.
AB  - The Kruppel-associated box (KRAB)-zinc finger protein ZBRK1 has been implicated
      in the transcriptional regulation of DNA damage-response genes that function in
      cell growth control and survival. Recently, we described a novel BRCA1-dependent
      C-terminal transcriptional repression domain (CTRD) within ZBRK1, the mode of
      repression of which is functionally distinguishable from that of the N-terminal
      KRAB repression domain within ZBRK1. The identification of BRCA1 binding
      competent but repression-defective CTRD mutants further revealed that BRCA1
      binding is necessary, but not sufficient, for ZBRK1 CTRD function. During an
      unbiased search for possible co-regulators of the CTRD, we identified ZBRK1
      itself, suggesting that ZBRK1 can oligomerize through its CTRD. Herein we explore
      the physical and functional requirements for ZBRK1 oligomerization in ZBRK1
      directed transcriptional repression. Protein interaction analyses confirmed that
      ZBRK1 can homo-oligomerize both in vitro and in vivo and further mapped the ZBRK1
      oligomerization domain to the CTRD C terminus. Biochemical analyses, including
      protein cross-linking and gel filtration chromatography, revealed that ZBRK1 homo
      oligomers exist as tetramers in solution. Functionally, ZBRK1 oligomerization
      facilitates ZBRK1-directed transcriptional repression through ZBRK1 response
      elements; requirements for oligomerization-dependent repression include the ZBRK1
      CTRD and KRAB repression domains but not the DNA binding activity of ZBRK1. These
      observations suggest that higher order oligomers of ZBRK1 may assemble on target
      ZBRK1 response elements through both protein-DNA and CTRD-dependent protein
      protein interactions. These findings thus reveal an unanticipated dual function
      for ZBRK1 in both DNA binding-dependent and -independent modes of transcriptional
      repression and further establish the CTRD as a novel protein interaction surface
      responsible for directing homotypic and heterotypic interactions necessary for
      ZBRK1-directed transcriptional repression.

PMID- 15496402
TI  - A structural basis for the acute effects of HIV protease inhibitors on GLUT4
      intrinsic activity.
AB  - Human immunodeficiency virus (HIV) protease inhibitors (PIs) act as reversible
      noncompetitive inhibitors of GLUT4 with binding affinities in the low micromolar
      range and are known to contribute to alterations in glucose homeostasis during
      treatment of HIV infection. As aspartyl protease inhibitors, these compounds all
      possess a core peptidomimetic structure together with flanking hydrophobic
      moieties. To determine the molecular basis for GLUT4 inhibition, a family of
      related oligopeptides containing structural elements found in PIs was screened
      for their ability to inhibit 2-deoxyglucose transport in primary rat adipocytes.
      The peptide oxybenzylcarbonyl-His-Phe-Phe-O-ethyl ester (zHFFe) was identified as
      a potent inhibitor of zero-trans glucose flux with a K(i) of 26 mum. Similar to
      PIs, transport inhibition by this peptide was acute, noncompetitive, and
      reversible. Within a Xenopus oocyte expression system, zHFFe acutely and
      reversibly inhibited GLUT4-mediated glucose uptake, whereas GLUT1 activity was
      unaffected at concentrations as high as 1 mm. The related photoactivatable
      peptide zHFF-p-benzoylphenylalanine-[(125)I]Tyr-O-ethyl ester selectively labeled
      GLUT4 in rat adipocytes and indinavir effectively protected against
      photolabeling. Furthermore, GLUT4 bound to a peptide affinity column containing
      the zHFF sequence and was eluted by indinavir. These data establish a structural
      basis for PI effects on GLUT4 activity and support the direct binding of PIs to
      the transport protein as the mechanism for acute inhibition of insulin-stimulated
      glucose uptake.

PMID- 15496403
TI  - A mathematical model of the folate cycle: new insights into folate homeostasis.
AB  - A mathematical model is developed for the folate cycle based on standard
      biochemical kinetics. We use the model to provide new insights into several
      different mechanisms of folate homeostasis. The model reproduces the known pool
      sizes of folate substrates and the fluxes through each of the loops of the folate
      cycle and has the qualitative behavior observed in a variety of experimental
      studies. Vitamin B(12) deficiency, modeled as a reduction in the V(max) of the
      methionine synthase reaction, results in a secondary folate deficiency via the
      accumulation of folate as 5-methyltetrahydrofolate (the "methyl trap"). One form
      of homeostasis is revealed by the fact that a 100-fold up-regulation of
      thymidylate synthase and dihydrofolate reductase (known to occur at the G(1)/S
      transition) dramatically increases pyrimidine production without affecting the
      other reactions of the folate cycle. The model also predicts that an almost total
      inhibition of dihydrofolate reductase is required to significantly inhibit the
      thymidylate synthase reaction, consistent with experimental and clinical studies
      on the effects of methotrexate. Sensitivity to variation in enzymatic parameters
      tends to be local in the cycle and inversely proportional to the number of
      reactions that interconvert two folate substrates. Another form of homeostasis is
      a consequence of the nonenzymatic binding of folate substrates to folate enzymes.
      Without folate binding, the velocities of the reactions decrease approximately
      linearly as total folate is decreased. In the presence of folate binding and
      allosteric inhibition, the velocities show a remarkable constancy as total folate
      is decreased.

PMID- 15496404
TI  - The type I Hsp40 zinc finger-like region is required for Hsp70 to capture non
      native polypeptides from Ydj1.
AB  - The cytosolic yeast Hsp40 Ydj1 contains a conserved zinc finger-like region
      (ZFLR), which has two zinc-binding domains (ZBD), that helps regulate and specify
      Hsp70 function. To investigate the mechanism for Ydj1 ZFLR action, ZBDI and ZBDII
      mutants were constructed and characterized. ZBDII mutants exhibited temperature
      sensitive growth defects, but yeast tolerated mutation of ZBDI. However, ZBDI and
      ZBDII mutants were defective at facilitating androgen receptor (AR) folding.
      Defective AR folding was associated with the accumulation of complexes between AR
      and Ydj1 ZFLR mutants and a reduction in Hsp70.AR complex formation. Purified
      Ydj1 ZBDI and ZBDII mutants could bind non-native polypeptides but could not
      deliver luciferase to Hsp70 and were defective at luciferase refolding.
      Interestingly, the ability of Ydj1 to synergize with Hsp70 to suppress thermally
      induced protein aggregation was blocked by mutation of ZBDII, but not ZBDI.
      Hence, ZBDII is required for yeast to survive heat stress because it is essential
      for Ydj1 to cooperate with Hsp70 to suppress protein aggregation. On the other
      hand, protein folding is dependent upon the action of both ZBDI and ZBDII because
      each is required for Hsp70 to capture non-native polypeptides from Ydj1.

PMID- 15496405
TI  - Two-dimensional transcriptome analysis in chemostat cultures. Combinatorial
      effects of oxygen availability and macronutrient limitation in Saccharomyces
      cerevisiae.
AB  - Genome-wide analysis of transcriptional regulation is generally studied by
      determining sets of "signature transcripts" that are up- or down-regulated
      relative to a reference situation when a single culture parameter or genetic
      modification is changed. This approach is especially relevant for defining small
      subsets of transcripts for use in high throughput, cost-effective diagnostic
      analyses. However, this approach may overlook the simultaneous control of
      transcription by more than one environmental parameter. This study represents the
      first quantitative assessment of the impact of transcriptional cross-regulation
      by different environmental parameters. As a model, we compared the response of
      aerobic as well as anaerobic chemostat cultures of the yeast Saccharomyces
      cerevisiae to growth limitation by four different macronutrients (carbon,
      nitrogen, phosphorus, and sulfur). The identity of the growth-limiting nutrient
      was shown to have a strong impact on the sets of transcripts that responded to
      oxygen availability and vice versa. We concluded that identification of reliable
      signature transcripts for specific environmental parameters can be obtained only
      by combining transcriptome data sets obtained under several sets of reference
      conditions. Furthermore, the two-dimensional approach to transcriptome analysis
      is a valuable new tool to study the interaction of different transcriptional
      regulation systems.

PMID- 15496406
TI  - Characterization of mammalian Ecm29, a 26 S proteasome-associated protein that
      localizes to the nucleus and membrane vesicles.
AB  - In addition to its thirty or so core subunits, a number of accessory proteins
      associate with the 26 S proteasome presumably to assist in substrate degradation
      or to localize the enzyme within cells. Among these proteins is ecm29p, a 200-kDa
      yeast protein that contains numerous HEAT repeats as well as a putative VHS
      domain. Higher eukaryotes possess a well conserved homolog of yeast ecm29p, and
      we produced antibodies to three peptides in the human Ecm29 sequence. The
      antibodies show that Ecm29 is present exclusively on 26 S proteasomes in HeLa
      cells and that Ecm29 levels vary markedly among mouse organs. Confocal
      immunofluorescence microscopy localizes Ecm29 to the centrosome and a subset of
      secretory compartments including endosomes, the ER and the ERGIC. Ecm29 is up
      regulated 2-3-fold in toxinresistant mutant CHO cells exhibiting increased rates
      of ER-associated degradation. Based on these results we propose that Ecm29 serves
      to couple the 26 S proteasome to secretory compartments engaged in quality
      control and to other sites of enhanced proteolysis.

PMID- 15496407
TI  - Transgenic mice overexpressing glutathione peroxidase 4 are protected against
      oxidative stress-induced apoptosis.
AB  - Glutathione peroxidase 4 (Gpx4) is uniquely involved in the detoxification of
      oxidative damage to membrane lipids. Our previous studies showed that Gpx4 is
      essential for mouse survival and that Gpx4 deficiency makes cells vulnerable to
      oxidative injury. In the present study, we generated two lines of transgenic mice
      overexpressing Gpx4 (Tg(GPX4) mice) using a genomic clone containing the human
      GPX4 gene. Both lines of Tg-(GPX4) mice, Tg5 and Tg6, had elevated levels of Gpx4
      (mRNA and protein) in all tissues investigated, and overexpression of Gpx4 did
      not cause alterations in activities of glutathione peroxidase 1, catalase, Cu/Zn
      superoxide dismutase, and manganese superoxide dismutase. The human GPX4
      transgene rescued the lethal phenotype of null mutation of the mouse Gpx4 gene,
      indicating that the transgene can replace the essential role of mouse Gpx4 in
      mouse development. Cell death induced by t-butylhydroperoxide and diquat was
      significantly less in murine embryonic fibroblasts from Tg(GPX4) mice compared
      with wild type mice. Liver damage and lipid peroxidation induced by diquat were
      reduced significantly in Tg(GPX4) mice. In addition, diquat-induced apoptosis was
      decreased in Tg(GPX4) mice, as evidenced by attenuated caspase-3 activation and
      reduced cytochrome c release from mitochondria. These data demonstrate that Gpx4
      plays a role in vivo in the mechanism of apoptosis induced by oxidative stress
      that most likely occurs through oxidative damage to mitochondrial phospholipids
      such as cardiolipin.

PMID- 15496408
TI  - The pancreatic duodenal homeobox-1 protein (Pdx-1) interacts with histone
      deacetylases Hdac-1 and Hdac-2 on low levels of glucose.
AB  - We have previously demonstrated that high concentrations of glucose stimulate
      insulin gene expression by causing hyperacetylation of histone H4 at the insulin
      gene promoter. Furthermore, we have shown that the glucose-mediated
      hyperacetylation of histone H4 depends on the recruitment of the histone
      acetyltransferase p300 by the beta cell-specific transcription factor Pdx-1. In
      this study, we demonstrate that the histone deacetylases Hdac-1 and Hdac-2 are
      rapidly recruited to the insulin promoter in the mouse insulinoma cell line MIN6
      when cells are switched from high to low glucose media. Moreover, we demonstrate
      that the beta cell-specific homeodomain protein Pdx-1 interacts with histone
      deacetylases Hdac-1 and Hdac-2 at low levels of glucose. In vitro studies
      indicate that the interaction between Pdx-1 and Hdac-1 or Hdac-2 is direct and
      requires the C terminus of Pdx-1. Treatment of MIN6 cells with okadaic acid,
      which inhibits the activity of protein phosphatases, abolishes the interaction of
      Pdx-1 with Hdac-1 and Hdac-2 on low levels of glucose, suggesting the requirement
      of a dephosphorylation event for this interaction to occur. These data indicate
      that insulin gene expression is decreased on low levels of glucose by recruitment
      of Hdac-1 and Hdac-2 to the insulin promoter by the transcription factor Pdx-1.

PMID- 15496409
TI  - Toll-like receptor 2 and mitogen- and stress-activated kinase 1 are effectors of
      Mycobacterium avium-induced cyclooxygenase-2 expression in macrophages.
AB  - Understanding how pathogenic mycobacteria subvert the protective immune response
      is crucial to the development of strategies aimed at controlling mycobacterial
      infections. Prostaglandin E(2) exerts an immunosuppressive function in the
      context of mycobacterial infection. Because cyclooxygenase-2 (COX-2) is a rate
      limiting enzyme in prostaglandin biosynthesis, there is a need to delineate the
      mechanisms through which pathogenic mycobacteria regulate COX-2 expression in
      macrophages. Our studies demonstrate that the NF-kappaB and CRE elements of the
      COX-2 promoter are critical to Mycobacterium avium-induced COX-2 gene expression.
      M. avium-triggered signaling originates at the Toll-like receptor 2 (TLR2). Ras
      associates with TLR2 and activates the mitogen-activated protein kinase (MAPK)
      extracellular signal-regulated kinase (ERK), whereas tumor necrosis factor
      receptor-associated factor 6 (TRAF6)/transforming growth factor beta-activated
      kinase 1 (TAK1)-dependent signaling activates p38 MAPK. Both ERK and p38 MAPK
      activation converge to regulate the activation of mitogen- and stress-activated
      kinase 1 (MSK1). MSK1 mediates the phosphorylation of the transcription factor
      CREB accounting for its stimulatory effect on CRE-dependent gene expression. M.
      avium-triggered cytoplasmic NF-kappaB activation following IkappaB
      phosphorylation is necessary but not sufficient for COX-2 promoter-driven gene
      expression. MSK1 activation is also essential for M. avium-triggered NF-kappaB
      dependent gene expression, presumably mediating nucleosomal modifications. These
      studies demonstrate that the nuclear kinase MSK1 is necessary in regulating the
      pathogen-driven expression of a gene by controlling two transcription factors.
      The attenuation of MSK1 may therefore have potential benefit in restricting
      survival of pathogenic mycobacteria in macrophages.

PMID- 15496410
TI  - Oligomerization of the {gamma}-aminobutyric acid transporter-1 is driven by an
      interplay of polar and hydrophobic interactions in transmembrane helix II.
AB  - The available evidence indicates that members of the neurotransmitter:sodium
      symporter family form constitutive oligomers. Their second transmembrane helix
      (TM2) contains a leucine heptad repeat proposed to be involved in
      oligomerization. In artificial transmembrane segments, interhelical interactions
      are stabilized by polar residues. We searched for these hydrogen bond donors in
      TM2 by mutating the five polar residues in TM2 of the gamma-aminobutyric acid
      transporter-1 (GAT1). We tested the ability of the resulting mutants to
      oligomerize by fluorescence microscopy, Foerster resonance energy transfer, and
      beta-lactamase fragment complementation. Of all generated mutants, only Y86A-
      (but not Y86F-), E101A-, E101Q-, and E101D-GAT1 were judged by these criteria to
      be deficient in oligomerization and were retained intracellularly. The
      observations are consistent with a model where the leucine heptad repeat in TM2
      drives a homophilic association that is stabilized by Tyr(86) and Glu(101);
      Tyr(86) participates in hydrophobic stacking. Glu(101) is in the a-position of
      the leucine heptad repeat (where positions 1-7 are denoted a-g, and each leucine
      is in the central d-position). Thus, Glu(101) is in the position predicted for
      the hydrogen bond donor (i.e. sandwiched between Leu(97) and Leu(104), which are
      one helical turn above and below Glu(101)). These key residues, namely Tyr(86)
      and Glu(101), are conserved in related transporters from archaeae to humans; they
      are therefore likely to support oligomeric assembly in transporter orthologs and
      possibly other proteins with multiple transmembrane segments.

PMID- 15496411
TI  - Multiple promoters direct expression of three AKAP12 isoforms with distinct
      subcellular and tissue distribution profiles.
AB  - A Kinase Anchoring Protein 12 (AKAP12; also known as src-suppressed C kinase
      substrate (SSeCKS) and Gravin) is a multivalent anchoring protein with tumor
      suppressor activity. Although expression of AKAP12 has been examined in a number
      of contexts, its expression control remains to be elucidated. Herein, we
      characterize the genomic organization of the AKAP12 locus, its regulatory
      regions, and the spatial distribution of the proteins encoded by the AKAP12 gene.
      Using comparative genomics and various wet-lab assays, we show that the AKAP12
      locus is organized as three separate transcription units that are governed by non
      redundant promoters coordinating distinct tissue expression profiles. The
      proteins encoded by the three AKAP12 isoforms (designated alpha, beta, and gamma)
      share >95% amino acid sequence identity but differ at their N termini. Analysis
      of the targeting of each isoform reveals distinct spatial distribution profiles.
      An N-terminal myristoylation motif present in AKAP12alpha is shown to be
      necessary and sufficient for targeted expression of this AKAP12 isoform to the
      endoplasmic reticulum, a novel subcellular compartment for AKAP12. Our results
      demonstrate heretofore unrecognized complexity within the AKAP12 locus and
      suggest a mechanism for genetic control of signaling specificity through distinct
      regulation of alternately targeted anchoring protein isoforms.

PMID- 15496412
TI  - Nerve growth factor receptor signaling induces histone acetyltransferase domain
      dependent nuclear translocation of p300/CREB-binding protein-associated factor
      and hGCN5 acetyltransferases.
AB  - The transcriptional coactivators, p300/CREB-binding protein-associated factor
      (PCAF) and hGCN5, are recruited to chromatin-remodeling complexes on enhancers of
      various gene promoters in response to growth factor stimulation. However, the
      molecular mechanisms by which surface receptor signals modulate the assembly of
      nuclear transcription complexes are not fully understood. Here we report that
      nerve growth factor receptor signaling induces nuclear translocation of PCAF and
      hGCN5 dependent upon the phosphorylation of Ser and Thr residues within their
      histone acetyltransferase domains, which requires activation of PI3K, Rsk2(pp90),
      and MSK-1. Neurotrophin stimulation induces p53(K320) acetylation by PCAF and
      transcriptionally activates p53-responsive enhancer elements within the
      p21(WAF/CIP1) promoter associated with G(1)/S arrest during neuronal
      differentiation. Most importantly, these findings represent the first evidence
      for signal-dependent nuclear translocation of PCAF and hGCN5 acetyltransferases
      and allude to a novel mechanism for ligand/receptor modulation of nuclear
      chromatin-remodeling complexes in neurons.

PMID- 15496413
TI  - N-WASP and WAVE2 acting downstream of phosphatidylinositol 3-kinase are required
      for myogenic cell migration induced by hepatocyte growth factor.
AB  - During skeletal muscle regeneration caused by injury, muscle satellite cells
      proliferate and migrate toward the site of muscle injury. This migration is
      mainly induced by hepatocyte growth factor (HGF) secreted by intact myofibers and
      also released from injured muscle. However, the intracellular machinery for the
      satellite cell migration has not been elucidated. To examine the mechanisms of
      satellite cell migration, we utilized satellite cell-derived mouse C2C12 skeletal
      muscle cells. HGF induced reorganization of actin cytoskeleton to form
      lamellipodia in C2C12 myoblasts. HGF treatment facilitated both nondirectional
      migration of the myoblasts in phagokinetic track assay and directional
      chemotactic migration toward HGF in a three-dimensional migration chamber assay.
      Endogenous N-WASP and WAVE2 were concentrated in the lamellipodia at the leading
      edge of the migrating cells. Moreover, exogenous expression of wild-type N-WASP
      or WAVE2 promoted lamellipodial formation and migration. By contrast, expression
      of the dominant-negative mutant of N-WASP or WAVE2 and knockdown of N-WASP or
      WAVE2 expression by the RNA interference prevented the HGF-induced lamellipodial
      formation and migration. When the cells were treated with LY294002, an inhibitor
      of phosphatidylinositol 3-kinase, the HGF-induced lamellipodial formation and
      migration were abrogated. These results imply that both N-WASP and WAVE2, which
      are activated downstream of phosphati-dylinositol 3-kinase, are required for the
      migration through the lamellipodial formation of C2C12 cells induced by HGF.

PMID- 15496414
TI  - Connective tissue growth factor (CTGF) is regulated by Wnt and bone morphogenetic
      proteins signaling in osteoblast differentiation of mesenchymal stem cells.
AB  - Osteoblast lineage-specific differentiation of mesenchymal stem cells is a well
      regulated but poorly understood process. Both bone morphogenetic proteins (BMPs)
      and Wnt signaling are implicated in regulating osteoblast differentiation and
      bone formation. Here we analyzed the expression profiles of mesenchymal stem
      cells stimulated with Wnt3A and osteogenic BMPs, and we identified connective
      tissue growth factor (CTGF) as a potential target of Wnt and BMP signaling. We
      confirmed the microarray results, and we demonstrated that CTGF was up-regulated
      at the early stage of BMP-9 and Wnt3A stimulations and that Wnt3A-regulated CTGF
      expression was beta-catenin-dependent. RNA interference-mediated knockdown of
      CTGF expression significantly diminished BMP-9-induced, but not Wnt3A-induced,
      osteogenic differentiation, suggesting that Wnt3A may also regulate osteoblast
      differentiation in a CTGF-independent fashion. However, constitutive expression
      of CTGF was shown to inhibit both BMP-9- and Wnt3A-induced osteogenic
      differentiation. Exogenous expression of CTGF was shown to promote cell migration
      and recruitment of mesenchymal stem cells. Our findings demonstrate that CTGF is
      up-regulated by Wnt3A and BMP-9 at the early stage of osteogenic differentiation,
      which may regulate the proliferation and recruitment of osteoprogenitor cells;
      however, CTGF is down-regulated as the differentiation potential of committed pre
      osteoblasts increases, strongly suggesting that tight regulation of CTGF
      expression may be essential for normal osteoblast differentiation of mesenchymal
      stem cells.

PMID- 15496415
TI  - Molecular isolation and characterization of a soluble isoform of activated
      leukocyte cell adhesion molecule that modulates endothelial cell function.
AB  - Cell adhesion molecules regulate a variety of endothelial cell functions such as
      migration, response to inflammation, and angiogenesis. Recently, activated
      leukocyte cell adhesion molecule (ALCAM), a member of the Ig superfamily, has
      been detected in the primitive subsets of hematopoietic cells and endothelial
      cells during embryogenesis. ALCAM supports the development of hematopoietic cells
      as well as enhancing capillary tube formation in vitro. Here, we isolated a novel
      soluble isoform of ALCAM (sALCAM) that is produced via alternative splicing.
      sALCAM contains the single amino-terminal Ig-like domain of ALCAM and lacks a
      transmembrane domain. When expressed in cultured cells, sALCAM was properly
      secreted into the media. Both ALCAM and sALCAM are expressed in a variety of
      cultured human endothelial cells. Notably, their transcripts were differentially
      regulated in human microvascular endothelial cells (HMVEC) upon tumor necrosis
      factor-alpha stimulation. ALCAM significantly enhanced tube formation of
      endothelial-like yolk sac cells on Matrigel, whereas it inhibited their migration
      in vitro. sALCAM completely abolished these effects of ALCAM. Furthermore, sALCAM
      enhanced migration of mock-transfected endothelial-like yolk sac cells that do
      not express ALCAM, indicating that sALCAM has an independent effect on cell
      migration in addition to modulating ALCAM function. In addition, sALCAM
      significantly enhanced migration of HMVEC, whereas it inhibited tube formation of
      HMVEC on Matrigel. sALCAM demonstrated an ability to bind ALCAM and partially
      inhibited ALCAM-ALCAM homophilic interactions. Taken together, these data
      characterize a novel soluble isoform of ALCAM that may have ALCAM-dependent and
      ALCAM-independent functions, providing further insights regarding the role of
      this adhesion molecule in the regulation of endothelial cell function.

PMID- 15496416
TI  - Association of paracellin-1 with ZO-1 augments the reabsorption of divalent
      cations in renal epithelial cells.
AB  - Paracellin-1 (PCLN-1) belongs to the claudin family of tight junction proteins
      and possibly plays a critical role in the reabsorption of magnesium and calcium.
      So far, the physiological properties of PCLN-1 have not been clarified. In the
      present study, we investigated whether PCLN-1 is associated with ZO-1. We also
      investigated whether (45)Ca(2+) transport across the paracellular barrier is
      affected by this association. In vitro binding analysis using glutathione S
      transferase fusion protein showed that the C-terminal TRV sequence, especially
      Thr and Val residues, of PCLN-1 interacts with ZO-1. Next, PCLN-1 was stably
      expressed in Madin-Darby canine kidney cells using a FLAG tagging vector. ZO-1
      was co-immunoprecipitated with the wild-type PCLN-1 and the alanine substitution
      (TAV) mutant. However, mutants of the deletion (Delta TRV) and the alanine
      substitution (ARV and TRA) inhibited the association of PCLN-1 with ZO-1.
      Confocal immunofluorescence demonstrated that the wild-type PCLN-1 and the TAV
      mutant localized in the tight junction along with ZO-1, but the Delta TRV, ARV,
      and TRA mutants were widely distributed in the lateral membrane including the
      tight junction area. Interestingly, monolayers of cells expressing the wild-type
      PCLN-1 and the TAV mutant showed higher activities of (45)Ca(2+) transport from
      apical to basal compartments, compared with those expressing the Delta TRV, ARV,
      and TRA mutants and the mock cells. (45)Ca(2+) transport was inhibited by
      increased magnesium concentration suggesting that magnesium and calcium were
      competitively transported by PCLN-1. It was noted that a positive electrical
      potential gradient enhanced (45)Ca(2+) transport from apical to basal
      compartments without affecting the opposite direction of transport. Thus, PCLN-1
      localizes to the tight junction followed by association with ZO-1, and the PCLN
      1.ZO-1 complex may play an essential role in the reabsorption of divalent cations
      in renal epithelial cells.

PMID- 15496418
TI  - IRF-2 is involved in up-regulation of nonmuscle myosin heavy chain II-A gene
      expression during phorbol ester-induced promyelocytic HL-60 differentiation.
AB  - Transcription of the nonmuscle myosin heavy chain II-A (NMHC-A) gene is regulated
      by various factors, including cell type, proliferation and differentiation stage,
      and extracellular stimuli. We have identified an intronic region (designated 32kb
      150), which is located 32 kb downstream of the transcription start sites in the
      human NMHC-A gene, as a transcriptional regulatory region. 32kb-150 contains an
      interferon-stimulated response element (ISRE). By using HeLa and NIH3T3 cells, in
      which NMHC-A is constitutively expressed, interferon regulatory factor (IRF)-2
      was found to be the only major protein, among the IRF family proteins, that bound
      to the ISRE in 32kb-150 both in vitro and in intact cells. IRF-2, which is known
      to either repress or activate target gene expression, acts as a transcriptional
      activator in the context of the 32kb-150 reporter gene. The carboxyl-terminal
      basic region of IRF-2 serves as an activation domain in this context. This is in
      contrast to its acting as a repressor domain in the context of the synthetic core
      ISRE. Furthermore, after treatment of promyelocytic HL-60 cells with 12-O
      tetradecanoylphorbol-13-acetate (TPA), which triggers differentiation into
      macrophages, both NMHC-A expression and IRF-2 expression were found to be up
      regulated with a similar time course. TPA treatment leads to recruitment of IRF-2
      to 32kb-150 of the endogenous NMHC-A gene and acetylation of the core histones
      surrounding this region. In addition, the ISRE in the 32kb-150 reporter gene
      recruits IRF-2 and mediates TPA-induced activation of a reporter gene in HL-60
      cells. Together, these results indicate that IRF-2 contributes to transcriptional
      activation of the NMHC-A gene via 32kb-150 during TPA-induced differentiation of
      HL-60 cells.

PMID- 15496417
TI  - Cyclophilin-A is bound through its peptidylprolyl isomerase domain to the
      cytoplasmic dynein motor protein complex.
AB  - Although cyclophilin A (CyP-A) is a relatively abundant small immunophilin
      present in the cytoplasm of all mammalian cells, its general function(s) in the
      absence of the immunosuppressant drug cyclosporin A is not known. In contrast,
      the high molecular weight hsp90-binding immunophilins appear to play a role in
      protein trafficking in that they have been shown to link glucocorticoid receptor
      hsp90 and p53.hsp90 complexes to the dynein motor protein for retrograde movement
      along microtubules. These immunophilins link to cytoplasmic dynein indirectly
      through the association of the immunophilin peptidylprolyl isomerase (PPIase)
      domain with dynamitin, a component of the dynein-associated dynactin complex
      (Galigniana, M. D., Harrell, J. M., O'Hagen, H. M., Ljungman, M., and Pratt, W.
      B. (2004) J. Biol. Chem. 279, 22483-22489). Here, we show that CyP-A exists in
      native heterocomplexes containing cytoplasmic dynein that can be formed in cell
      free systems. Prolyl isomerase activity is not required for forming the dynein
      complex, but the PPIase domain fragment of FKBP52 blocks complex formation and
      CyP-A binds to dynamitin in a PPIase domain-dependent manner. CyP-A
      heterocomplexes containing tubulin and dynein can be formed in cytosol prepared
      under microtubule-stabilizing conditions, and CyP-A colocalizes in mouse
      fibroblasts with microtubules. Colocalization with microtubules is disrupted by
      overexpression of the PPIase domain fragment. Thus, we conclude that CyP-A
      associates in vitro and in vivo with the dynein/dynactin motor protein complex
      and we suggest that CyP-A may perform a general function related to the binding
      of cargo for retrograde movement along microtubules.

PMID- 15496419
TI  - Human ADA3 binds to estrogen receptor (ER) and functions as a coactivator for ER
      mediated transactivation.
AB  - We have recently identified the hADA3 protein, the human homologue of yeast
      transcriptional coactivator yADA3, as a novel HPV16 E6 target. Using ectopic
      expression approaches, we further demonstrated that hADA3 directly binds to the 9
      cis retinoic acid receptors alpha and beta, and functions as a coactivator for
      retinoid receptor-mediated transcriptional activation. Here, we examined the role
      of endogenous hADA3 as a coactivator for estrogen receptor (ER), an important
      member of the nuclear hormone receptor superfamily. We show that ADA3 directly
      interacts with ER alpha and ER beta. Using the chromatin immunoprecipitation
      assay, we also show that hADA3 is a component of the activator complexes bound to
      the native ER response element within the promoter of the estrogen-responsive
      gene pS2. Furthermore, using an ER response element-luciferase reporter, we show
      that overexpression of ADA3 enhances the ER alpha- and ER beta-mediated sequence
      specific transactivation. Reverse transcription-PCR analysis showed an ADA3
      mediated increase in estrogen-induced expression of the endogenous pS2 gene. More
      importantly, using RNA interference against hADA3, we demonstrate that inhibition
      of endogenous hADA3 inhibited ER-mediated transactivation and the estrogen
      induced increase in the expression of pS2, cathepsin D, and progesterone
      receptor, three widely known ER-responsive genes. The HPV E6 protein, by
      targeting hADA3 for degradation, inhibited the ER alpha-mediated transactivation
      and the protein expression of ER target genes. Thus, our results demonstrate that
      ADA3 directly binds to human estrogen receptor and enhances the transcription of
      ER-responsive genes, suggesting a broader role of mammalian hADA3 as a
      coactivator of nuclear hormone receptors and the potential role of these pathways
      in HPV oncogenesis.

PMID- 15496420
TI  - The poxvirus p28 virulence factor is an E3 ubiquitin ligase.
AB  - A majority of the orthopoxviruses, including the variola virus that causes the
      dreaded smallpox disease, encode a highly conserved 28-kDa protein with a classic
      RING finger sequence motif (C(3)HC(4)) at their carboxyl-terminal domains. The
      RING domain of p28 has been shown to be a critical determinant of viral virulence
      for the ectromelia virus (mousepox virus) in a murine infection model (Senkevich,
      T. G., Koonin, E. V., and Buller, R. M. (1994) Virology 198, 118-128). Here, we
      demonstrate that the p28 proteins encoded by the ectromelia virus and the variola
      virus possess E3 ubiquitin ligase activity in biochemical assays as well as in
      cultured mammalian cells. Point mutations disrupting the RING finger domain of
      p28 completely abolish its E3 ligase activity. In addition, p28 functions
      cooperatively with Ubc4 and UbcH5c, the E2 conjugating enzymes involved in 26 S
      proteasome degradation of protein targets. Moreover, p28 catalyzes the formation
      of Lys-63-linked polyubiquitin chains in the presence of Ubc13/Uev1A, a
      heterodimeric E2 conjugating enzyme, indicating that p28 may regulate the
      biological activity of its cognate viral and/or host cell target(s) by Lys-63
      linked ubiquitin multimers. We thus conclude that the poxvirus p28 virulence
      factor is a new member of the RING finger E3 ubiquitin ligase family and has a
      unique polyubiquitylation activity. We propose that the E3 ligase activity of the
      p28 virulence factor may be targeted for therapeutic intervention against
      infections by the variola virus and other poxviruses.

PMID- 15496421
TI  - Somatic deletion events occur during early embryonic development and modify the
      extent of CAG expansion in subsequent generations.
AB  - Alterations in trinucleotide repeat length during transmission are important in
      the pathophysiology of Huntington's disease (HD). However, it is not well
      understood where, when and by what mechanism expansion occurs. We have followed
      the fate of CAG repeats during development in mice that can [hHD(-/+)/Msh2(+/+)]
      or cannot [hHD(-/+)/Msh2(-/-)] expand their repeats. Here we show that long
      repeats are shortened during somatic replication early in the embryo of the
      progeny. Our data point to different mechanisms for expansion and deletion.
      Deletions arise during replication, do not depend on the presence of Msh2 and are
      largely restricted to early development. In contrast, expansions depend on strand
      break repair, require the presence of Msh2 and occur later in development.
      Overall, these results suggest that deletions in early development serve as a
      safeguard of the genome and protect against expansion of the disease-range
      repeats during transmission.

PMID- 15496422
TI  - Lowering of Pkd1 expression is sufficient to cause polycystic kidney disease.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is a major cause of renal
      failure and is characterized by the formation of many fluid-filled cysts in the
      kidneys. It is a systemic disorder that is caused by mutations in PKD1 or PKD2.
      Homozygous inactivation of these genes at the cellular level, by a 'two-hit'
      mechanism, has been implicated in cyst formation but does not seem to be the sole
      mechanism for cystogenesis. We have generated a novel mouse model with a
      hypomorphic Pkd1 allele, Pkd1(nl), harbouring an intronic neomycin-selectable
      marker. This selection cassette causes aberrant splicing of intron 1, yielding
      only 13-20% normally spliced Pkd1 transcripts in the majority of homozygous
      Pkd1(nl) mice. Homozygous Pkd1(nl) mice are viable, showing bilaterally enlarged
      polycystic kidneys. This is in contrast to homozygous knock-out mice, which are
      embryonic lethal, and heterozygous knock-out mice that show only a very mild
      cystic phenotype. In addition, homozygous Pkd1(nl) mice showed dilatations of
      pancreatic and liver bile ducts, and the mice had cardiovascular abnormalities,
      pathogenic features similar to the human ADPKD phenotype. Removal of the neomycin
      selection-cassette restored the phenotype of wild-type mice. These results show
      that a reduced dosage of Pkd1 is sufficient to initiate cystogenesis and vascular
      defects and indicate that low Pkd1 gene expression levels can overcome the
      embryonic lethality seen in Pkd1 knock-out mice. We propose that in patients
      reduced PKD1 expression of the normal allele below a critical level, due to
      genetic, environmental or stochastic factors, may lead to cyst formation in the
      kidneys and other clinical features of ADPKD.

PMID- 15496423
TI  - Seckel syndrome exhibits cellular features demonstrating defects in the ATR
      signalling pathway.
AB  - To date, the only reported genetic defect identified in the developmental
      disorder, Seckel syndrome, is a mutation in ataxia telangiectasia and Rad3
      related protein (ATR). Seckel syndrome is clinically and genetically
      heterogeneous and whether defects in ATR significantly contribute to Seckel
      syndrome is unclear. Firstly, we characterize ATR-Seckel cells for their response
      to DNA damage. ATR-Seckel cells display impaired phosphorylation of ATR-dependent
      substrates, impaired G2/M checkpoint arrest and elevated micronucleus (MN)
      formation following exposure to UV and agents that cause replication stalling. We
      describe a novel phenotype, designated nuclear fragmentation (NF), that occurs
      following replication arrest. Finally, we report that ATR-Seckel cells have an
      endogenously increased number of centrosomes in mitotic cells demonstrating a
      novel role for ATR in regulating centrosome stability. We exploit these
      phenotypes to examine cell lines derived from additional unrelated Seckel
      syndrome patients. We show that impaired phosphorylation of ATR-dependent
      substrates is a common but not invariant feature of Seckel syndrome cell lines.
      In contrast, all cell lines displayed defective G2/M arrest, increased levels of
      NF and MN formation following exposure to agents that cause replication stalling.
      All the Seckel syndrome cell lines examined showed increased endogenous
      centrosome numbers. Though ATR cDNA can complement the defects in ATR-Seckel
      cells, it failed to complement any of the additional cell lines. We conclude that
      Seckel syndrome represents a further damage response disorder that is uniquely
      associated with defects in the ATR-signalling pathway resulting in failed
      checkpoint arrest following exposure to replication fork stalling.

PMID- 15496424
TI  - Branch site haplotypes that control alternative splicing.
AB  - We show that the allele-dependent expression of transcripts encoding soluble HLA
      DQbeta chains is determined by branchpoint sequence (BPS) haplotypes in DQB1
      intron 3. BPS RNAs associated with low inclusion of the transmembrane exon in
      mature transcripts showed impaired binding to splicing factor 1 (SF1), indicating
      that alternative splicing of DQB1 is controlled by differential BPS recognition
      early during spliceosome assembly. We also demonstrate that naturally occurring
      human BPS point mutations that alter splicing and lead to recognizable phenotypes
      cluster in BP and in position -2 relative to BP, implicating impaired SF1-BPS
      interactions in disease-associated BPS substitutions. Coding DNA variants
      produced smaller fluctuations of exon inclusion levels than random exonic
      substitutions, consistent with a selection against coding mutations that alter
      their own exonization. Finally, proximal splicing in this multi-allelic reporter
      system was promoted by at least seven SR proteins and repressed by hnRNPs F, H
      and I, supporting an extensive antagonism of factors balancing the splice site
      selection. These results provide the molecular basis for the haplotype-specific
      expression of soluble DQbeta, improve prediction of intronic point mutations and
      indicate how extraordinary, selection-driven DNA variability in HLA affects pre
      mRNA splicing.

PMID- 15496425
TI  - MUSK, a new target for mutations causing congenital myasthenic syndrome.
AB  - We report the first case of a human neuromuscular transmission dysfunction due to
      mutations in the gene encoding the muscle-specific receptor tyrosine kinase
      (MuSK). Gene analysis identified two heteroallelic mutations, a frameshift
      mutation (c.220insC) and a missense mutation (V790M). The muscle biopsy showed
      dramatic pre- and postsynaptic structural abnormalities of the neuromuscular
      junction and severe decrease in acetylcholine receptor (AChR) epsilon-subunit and
      MuSK expression. In vitro and in vivo expression experiments were performed using
      mutant MuSK reproducing the human mutations. The frameshift mutation led to the
      absence of MuSK expression. The missense mutation did not affect MuSK catalytic
      kinase activity but diminished expression and stability of MuSK leading to
      decreased agrin-dependent AChR aggregation, a critical step in the formation of
      the neuromuscular junction. In electroporated mouse muscle, overexpression of the
      missense mutation induced, within a week, a phenotype similar to the patient
      muscle biopsy: a severe decrease in synaptic AChR and an aberrant axonal
      outgrowth. These results strongly suggest that the missense mutation, in the
      presence of a null mutation on the other allele, is responsible for the dramatic
      synaptic changes observed in the patient.

PMID- 15496426
TI  - Polymorphisms in the prostaglandin E2 receptor subtype 2 gene confer
      susceptibility to aspirin-intolerant asthma: a candidate gene approach.
AB  - Aspirin-intolerant asthma (AIA) is a subtype of bronchial asthma characterized by
      development of bronchoconstriction evoked by non-steroidal anti-inflammatory
      drugs (NSAIDs). NSAIDs inhibit the cyclooxygenase pathway, leading to enhancement
      of the lipoxygenase pathway. We evaluated allelic association of 370 single
      nucleotide polymorphisms (SNPs) of 63 candidate genes, mostly from the
      arachidonic acid metabolic cascade, with AIA. After two rounds of screening with
      198 AIA patients, multiple SNPs in the prostaglandin E(2) receptor subtype 2
      (EP2) gene were associated with AIA (P<0.05). Among the 77 SNPs identified in the
      EP2 gene, we selected 17 SNPs on the basis of linkage disequilibrium and allelic
      frequencies (minor allele frequency >0.1) for further association study. SNPs in
      the promoter region of the EP2 gene, uS5, uS5b, and uS7, were significantly
      associated with AIA (permutation P=0.039-0.001). Analysis of haplotypes
      constructed according to the LD pattern showed a significant association with AIA
      (permutation P=0.001). The most significantly associated SNP, uS5, located in the
      regulatory region of the EP2 gene, was in a STATs-binding consensus sequence [AIA
      31.1% versus control 22.1% (permutation P=0.0016) or versus aspirin-tolerant
      asthma 22.2% (permutation P=0.0017)]. Although STAT1 binding was not observed in
      gel mobility shift assay with HeLa nuclear extract, an unidentified protein was
      specifically bound to the allelic sequence. In in vitro reporter assay in HCT116
      cells, the site containing the uS5 allele showed reduced transcription activity.
      Taken together, these results suggest that uS5 allele serves as a target of a
      transcription repressor protein. A functional SNP of the EP2 gene associated with
      risk of AIA should decrease the transcription level, resulting in reduction of
      the PGE(2) braking mechanism of inflammation and involvement in the molecular
      mechanism underlying AIA.

PMID- 15496427
TI  - Prediction of sensitivity of advanced non-small cell lung cancers to gefitinib
      (Iressa, ZD1839).
AB  - Gefitinib (Iressa, ZD1839), an inhibitor of epidermal growth factor receptor
      tyrosine kinase, has shown potent anti-tumor effects and improved symptoms and
      quality-of-life of a subset of patients with advanced non-small cell lung cancer
      (NSCLC). However, a large portion of the patients showed no effect to this agent.
      To establish a method to predict the response of NSCLC patients to gefitinib, we
      used a genome-wide cDNA microarray to analyze 33 biopsy samples of advanced NSCLC
      from patients who had been treated with an identical protocol of second to
      seventh line gefitinib monotherapy. We identified 51 genes whose expression
      differed significantly between seven responders and 10 non-responders to the
      drug. We selected the 12 genes that showed the most significant differences to
      establish a numerical scoring system (GRS, gefitinib response score), for
      predicting response to gefitinib treatment. The GRS system clearly separated the
      two groups without any overlap, and accurately predicted responses to the drug in
      16 additional NSCLC cases. The system was further validated by the semi
      quantitative RT-PCR, immunohistochemistry and ELISA for serological test.
      Moreover, we proved that the anti-apoptotic activity of amphiregulin, a protein
      that was significantly over-expressed in non-responders but undetectable in
      responders, leads to resistance of NSCLC cells to gefitinib in vitro. Our results
      suggested that sensitivity of a given NSCLC to gefitinib can be predicted
      according to expression levels of a defined set of genes that may biologically
      affect drug sensitivity and survival of lung cancer cells. Our scoring system
      might eventually lead to achievement of personalized therapy for NSCLC patients.

PMID- 15496428
TI  - The gene for paroxysmal non-kinesigenic dyskinesia encodes an enzyme in a stress
      response pathway.
AB  - Paroxysmal non-kinesigenic dyskinesia (PNKD) is characterized by spontaneous
      hyperkinetic attacks that are precipitated by alcohol, coffee, stress and
      fatigue. We report mutations in the myofibrillogenesis regulator 1 (MR-1) gene
      causing PNKD in 50 individuals from eight families. The mutations cause changes
      (Ala to Val) in the N-terminal region of two MR-1 isoforms. The MR-1L isoform is
      specifically expressed in brain and is localized to the cell membrane while the
      MR-1S isoform is ubiquitously expressed and shows diffuse cytoplasmic and nuclear
      localization. Bioinformatic analysis reveals that the MR-1 gene is homologous to
      the hydroxyacylglutathione hydrolase (HAGH) gene. HAGH functions in a pathway to
      detoxify methylglyoxal, a compound present in coffee and alcoholic beverages and
      produced as a by-product of oxidative stress. Our results suggest a mechanism
      whereby alcohol, coffee and stress may act as precipitants of attacks in PNKD.
      Stress response pathways will be important areas for elucidation of episodic
      disease genetics where stress is a common precipitant of many common disorders
      like epilepsy, migraine and cardiac arrhythmias.

PMID- 15496429
TI  - Transcription factor MEF2A mutations in patients with coronary artery disease.
AB  - Coronary artery disease (CAD), including its most serious complication myocardial
      infraction (MI), is the leading cause of death in the US and developed countries.
      We recently discovered that a seven-amino acid deletion in MEF2A, a transcription
      factor with a high level of expression in the endothelium of coronary arteries,
      co-segregates with CAD/MI in one family, and it suppresses transcription
      activation activity of MEF2A by a dominant-negative mechanism. In this study, we
      used single-strand conformation polymorphism and DNA sequence analyses to
      identify mutations in MEF2A in 207 independent CAD/MI patients and 191 controls
      with normal angiograms. We identified three novel mutations in exon 7 of MEF2A in
      four of 207 CAD/MI patients (1.93%). No mutations were detected in the 191
      controls. The mutations identified here include N263S identified in two
      independent CAD patients, P279L in one patient and his father with the diagnosis
      of CAD and G283D in one patient. These mutations are clustered within or close to
      the major transcriptional activation domain of MEF2A. They significantly reduce
      the transcriptional activation activity of MEF2A and act by a loss-of-function
      mechanism. The gene carriers with loss-of-function mutations appear to be
      associated with less severe CAD. These results suggest that CAD/MI can result
      from a spectrum of MEF2A transcription dysfunctions ranging from loss-of-function
      to dominant-negative suppression and that a significant percent of the CAD/MI
      population (1.93%) may carry mutations in MEF2A, although further definition of
      the prevalence of MEF2A mutations is warranted.

PMID- 15496430
TI  - Huntingtin-associated protein 1 (Hap1) mutant mice bypassing the early postnatal
      lethality are neuroanatomically normal and fertile but display growth
      retardation.
AB  - Huntingtin-associated protein 1 (Hap1) is the first huntingtin interacting
      protein identified in a yeast two-hybrid screen. Although Hap1 expression has
      been demonstrated in neuronal and non-neuronal tissues, its molecular role is
      poorly understood. Recently, it has been shown that targeted disruption of Hap1
      in mice results in early postnatal death as a result of depressed feeding
      behavior. Although this result clearly demonstrates an essential role of Hap1 in
      postnatal feeding, the mechanisms leading to this deficiency, as well as the role
      of Hap1 in adults, remain unclear. Here we show that Hap1 null mutants display
      suckling defects and die within the first days after birth due to starvation.
      Upon reduction of the litter size, some mutants survive into adulthood and
      display growth retardation with no apparent brain or behavioral abnormalities,
      suggesting that Hap1 function is essential only for early postnatal feeding
      behavior. Using a conditional gene repair strategy, we also show that the early
      lethality can be rescued if Hap1 expression is restored in neuronal cells before
      birth. Furthermore, no synergism was observed between Hap1 and huntingtin
      mutation during mouse development. Our results demonstrate that Hap1 has a
      fundamental role in regulating postnatal feeding in the first 2 weeks after birth
      and a non-essential role in the adult mouse.

PMID- 15496431
TI  - Myotonic dystrophy type 1 is associated with nuclear foci of mutant RNA,
      sequestration of muscleblind proteins and deregulated alternative splicing in
      neurons.
AB  - Myotonic dystrophy type 1 (DM1) is caused by expansion of a CTG repeat in the
      DMPK gene. In skeletal muscles, DM1 may involve a novel, RNA-dominant disease
      mechanism in which transcripts from the mutant DMPK allele accumulate in the
      nucleus and compromise the regulation of alternative splicing. Here we show
      evidence for a similar disease mechanism in brain. Examination of post-mortem DM1
      tissue by fluorescence in situ hybridization indicates that the mutant DMPK mRNA,
      with its expanded CUG repeat in the 3'-untranslated region, is widely expressed
      in cortical and subcortical neurons. The mutant transcripts accumulate in
      discrete foci within neuronal nuclei. Proteins in the muscleblind family are
      recruited into the RNA foci and depleted elsewhere in the nucleoplasm. In
      parallel, a subset of neuronal pre-mRNAs show abnormal regulation of alternative
      splicing. These observations suggest that CNS impairment in DM1 may result from a
      deleterious gain-of-function by mutant DMPK mRNA.

PMID- 15496432
TI  - Heterologous mitochondrial DNA recombination in human cells.
AB  - Inter-molecular heterologous mitochondrial DNA (mtDNA) recombination is known to
      occur in yeast and plants. Nevertheless, its occurrence in human cells is still
      controversial. To address this issue we have fused two human cytoplasmic hybrid
      cell lines, each containing a distinct pathogenic mtDNA mutation and specific
      sets of genetic markers. In this hybrid model, we found direct evidence of
      recombination between these two mtDNA haplotypes. Recombinant mtDNA molecules in
      the hybrid cells were identified using three independent experimental approaches.
      First, recombinant molecules containing genetic markers from both parental
      alleles were demonstrated with restriction fragment length polymorphism of
      polymerase chain reaction products, by measuring the relative frequencies of each
      marker. Second, fragments of recombinant mtDNA were cloned and sequenced to
      identify the regions involved in the recombination events. Finally, recombinant
      molecules were demonstrated directly by Southern blot using appropriate
      combinations of polymorphic restriction sites and probes. This combined approach
      confirmed the existence of heterogeneous species of recombinant mtDNA molecules
      in the hybrid cells. These findings have important implications for mtDNA-related
      diseases, the interpretation of human evolution and population genetics and
      forensic analyses based on mtDNA genotyping.

PMID- 15496433
TI  - In vitro biomarker discovery for atherosclerosis by proteomics.
AB  - The purpose of this study was to identify in vitro and then prioritize a
      tractable set of protein biomarker candidates of atherosclerosis that may
      eventually be developed to measure the extent, progression, regression, and
      stability of atherosclerotic lesions. A study was conducted using an in
      vitro"foam cell" model based on the stimulation of differentiated THP1 cells with
      oxidized low-density lipoprotein (oxidized LDL) as compared with low-density
      lipoprotein (LDL). Analysis of the proteins contained in the cell supernatant
      using proteome scanning technology identified 59 proteins as being increased, 57
      with no statistically measurable difference, and 17 decreasing in abundance
      following treatment with oxidized LDL, as compared with LDL. From the up
      regulated list, proteins were prioritized based on their analytical confidence as
      well as their relevance to atherosclerosis pathways. Within the group of
      increased abundance, seven families of proteins were of particular interest:
      fatty acid-binding proteins, chitinase-like enzymes, cyclophilins, cathepsins,
      proteoglycans, urokinase-type plasminogen activator receptor, and a macrophage
      scavenger receptor.

PMID- 15496434
TI  - Mental stress and sudden cardiac death: asymmetric midbrain activity as a linking
      mechanism.
AB  - Patients with specific neurological, psychiatric or cardiovascular conditions are
      at enhanced risk of cardiac arrhythmia and sudden death. The neurogenic
      mechanisms are poorly understood. However, in many cases, stress may precipitate
      cardiac arrhythmia and sudden death in vulnerable patients, presumably via
      centrally driven autonomic nervous system responses. From a cardiological
      perspective, the likelihood of arrhythmia is strongly associated with
      abnormalities in electrical repolarization (recovery) of the heart muscle after
      each contraction. Inhomogeneous and asymmetric repolarization, reflected in ECG T
      wave abnormalities, is associated with a greatly increased risk of arrhythmia,
      i.e. a proarrhythmic state. We therefore undertook a study to identify the brain
      mechanisms by which stress can induce cardiac arrhythmia through efferent
      autonomic drive. We recruited a typical group of 10 out-patients attending a
      cardiological clinic. We simultaneously measured brain activity, using H2(15)O
      PET, and the proarrhythmic state of the heart, using ECG, during mental and
      physical stress challenges and corresponding control conditions. Proarrhythmic
      changes in the heart were quantified from two ECG-derived measures of
      repolarization inhomogeneity and were related to changes in magnitude and
      lateralization of regional brain activity reflected in regional cerebral blood
      flow. Across the patient group, we observed a robust positive relationship
      between right-lateralized asymmetry in midbrain activity and proarrhythmic
      abnormalities of cardiac repolarization (apparent in two independent ECG
      measures) during stress. This association between stress-induced lateralization
      of midbrain activity and enhanced arrhythmic vulnerability provides empirical
      support for a putative mechanism for stress-induced sudden death, wherein
      lateralization of central autonomic drive during stress results in imbalanced
      activity in right and left cardiac sympathetic nerves. A right-left asymmetry in
      sympathetic drive across the surface of the heart disrupts the
      electrophysiological homogeneity of ventricular repolarization, predisposing to
      arrhythmia. Our findings highlight a proximal brain basis for stress-induced
      cardiac arrhythmic vulnerability.

PMID- 15496435
TI  - Motor inhibition in patients with Gilles de la Tourette syndrome: functional
      activation patterns as revealed by EEG coherence.
AB  - There is considerable evidence that Gilles de la Tourette syndrome (TS) is due to
      frontal-striatal dysfunction. Here we determine whether adaptive cortical changes
      occur that might ameliorate the effects of this dysfunction. Specifically we test
      the hypothesis that increased interactions between selected cortical areas may
      help compensate through strengthened inhibition of inappropriate motor responses.
      To this end we recorded EEG in nine unmedicated patients with TS and nine age
      matched healthy subjects during a variety of behavioural tasks related to motor
      inhibition. Functional connectivity between cortical areas was assessed by means
      of EEG coherence in the alpha frequency band (8-12 Hz). Elevated coherence was
      found between sensorimotor areas and the prefrontal and mesial frontal cortex
      during the acute voluntary suppression of tics. The same frontomesial network was
      overactive in TS patients compared with healthy subjects even when suppression of
      voluntary movement rather than tics was required during a Go-NoGo task.
      Behavioural performance in the Go-NoGo task was not different between patients
      and controls, confirming that the elevated frontomesial coherence in TS was
      likely to be adaptive rather than functionally disruptive. It is concluded that
      the gain in inhibitory frontomesial cortical networks is adaptively heightened in
      TS, and that the same network can also be engaged in the voluntary suppression of
      tics.

PMID- 15496436
TI  - Six-month recovery from mild to moderate Traumatic Brain Injury: the role of APOE
      epsilon4 allele.
AB  - The possession of at least one APOE-epsilon4 allele may be linked to poor outcome
      in patients with predominantly severe traumatic brain injury (TBI). In mild TBI,
      which accounts for approximately 85% of all cases, the role of the APOE-epsilon4
      allele is less clear. Studies completed to date have relied on brief cognitive
      assessments or coarse measures of global functioning, thereby limiting their
      conclusions. Our study investigated the influence of the APOE-epsilon4 allele in
      a prospective sample of 90 adults with mild to moderate TBI in whom
      neuropsychiatric outcome 6 months after injury was assessed as follows: (i) a
      detailed neuropsychological battery; (ii) an index of emotional distress (General
      Health Questionnaire); (iii) a diagnosis of major depression (Structured Clinical
      Interview for DSM-IV); (iv) a measure of global functioning (Glasgow Outcome
      Scale); (v) an index of psychosocial outcome (Rivermead Head Injury Follow-up
      Questionnaire); and (vi) symptoms of persistent post-concussion disorder
      (Rivermead Post-Concussion Symptoms Questionnaire). No association was found
      between the presence of the APOE-epsilon4 allele and poor outcome across all
      measures. Given the homogeneous nature of our sample (mild to moderate injury
      severity), the uniform follow-up period (6 months) and the comprehensive markers
      of recovery used, our data suggest that the APOE-epsilon4 allele does not
      adversely impact outcome in this group of TBI patients.

PMID- 15496437
TI  - The impact of obesity on rising medical spending.
AB  - Obese people incur higher health care costs at a given point in time, but how
      rising obesity rates affect spending growth over time is unknown. We estimate
      obesity-attributable health care spending increases between 1987 and 2001.
      Increases in the proportion of and spending on obese people relative to people of
      normal weight account for 27 percent of the rise in inflation-adjusted per capita
      spending between 1987 and 2001; spending for diabetes, 38 percent; spending for
      hyperlipidemia, 22 percent; and spending for heart disease, 41 percent. Increases
      in obesity prevalence alone account for 12 percent of the growth in health
      spending.

PMID- 15496438
TI  - Conserved and acquired features of neurogenin1 regulation.
AB  - The telencephalon shows vast morphological variations among different vertebrate
      groups. The transcription factor neurogenin1 (ngn1) controls neurogenesis in the
      mouse pallium and is also expressed in the dorsal telencephalon of the
      evolutionary distant zebrafish. The upstream regions of the zebrafish and
      mammalian ngn1 loci harbour several stretches of conserved sequences. Here, we
      show that the upstream region of zebrafish ngn1 is capable of faithfully
      recapitulating endogenous expression in the zebrafish and mouse telencephalon. A
      single conserved regulatory region is essential for dorsal telencephalic
      expression in the zebrafish, and for expression in the dorsal pallium of the
      mouse. However, a second conserved region that is inactive in the fish
      telencephalon is necessary for expression in the lateral pallium of mouse
      embryos. This regulatory region, which drives expression in the zebrafish
      diencephalon and hindbrain, is dependent on Pax6 activity and binds recombinant
      Pax6 in vitro. Thus, the regulatory elements of ngn1 appear to be conserved among
      vertebrates, with certain differences being incorporated in the utilisation of
      these enhancers, for the acquisition of more advanced features in amniotes. Our
      data provide evidence for the co-option of regulatory regions as a mechanism of
      evolutionary diversification of expression patterns, and suggest that an
      alteration in Pax6 expression was crucial in neocortex evolution.

PMID- 15496439
TI  - Negative regulation of Smad2 by PIASy is required for proper Xenopus mesoderm
      formation.
AB  - Mesoderm induction and patterning are primarily regulated by the concentration of
      locally expressed morphogens such as members of the TGFbetasuperfamily. Smad2
      functions as a transcription factor to regulate expression of mesodermal genes
      downstream of such morphogens. We have identified Xenopus PIASy (XPIASy), a
      member of the PIAS family, by yeast two-hybrid screening using Xenopus Smad2
      (XSmad2) as a bait. During mesoderm induction, XPIASy is expressed in the animal
      half of embryos with a ventral high-dorsal low gradient at the marginal zone.
      XPIASy expression is positively and negatively regulated by activities of the
      XSmad2 and Wnt pathways, respectively. Interestingly, inhibition of XPIASy by
      morpholinos induces elongation of animal caps with induction of mesoderm genes
      even in the absence of their morphogen-mediated activation. In addition, their
      introduction into the ventral marginal zone results in a secondary axis
      formation. Gain-of-function analysis revealed that XPIASy inhibits mesoderm
      induction by specific and direct downregulation of XSmad2 transcriptional
      activity. These observations indicate that XPIASy functions as an essential
      negative regulator of the XSmad2 pathway to ensure proper mesoderm induction at
      the appropriate time and in the appropriate region, and suggest that both the
      initial step of morphogen-mediated activation of the XSmad2 pathway and
      regulation of the final downstream transcription step have crucial roles in
      mesoderm induction and patterning.

PMID- 15496440
TI  - Drosophila deltex mediates suppressor of Hairless-independent and late-endosomal
      activation of Notch signaling.
AB  - Notch (N) signaling is an evolutionarily conserved mechanism that regulates many
      cell-fate decisions. deltex (dx) encodes an E3-ubiquitin ligase that binds to the
      intracellular domain of N and positively regulates N signaling. However, the
      precise mechanism of Dx action is unknown. Here, we found that Dx was required
      and sufficient to activate the expression of gene targets of the canonical Su(H)
      dependent N signaling pathway. Although Dx required N and a cis-acting element
      that overlaps with the Su(H)-binding site, Dx activated a target enhancer of N
      signaling, the dorsoventral compartment boundary enhancer of vestigial (vgBE), in
      a manner that was independent of the Delta (Dl)/Serrate (Ser) ligands- or Su(H).
      Dx caused N to be moved from the apical cell surface into the late-endosome,
      where it accumulated stably and co-localized with Dx. Consistent with this, the
      dx gene was required for the presence of N in the endocytic vesicles. Finally,
      blocking the N transportation from the plasma membrane to the late-endosome by a
      dominant-negative form of Rab5 inhibited the Dx-mediated activation of N
      signaling, suggesting that the accumulation of N in the late-endosome was
      required for the Dx-mediated Su(H)-independent N signaling.

PMID- 15496441
TI  - Spatial pattern of sonic hedgehog signaling through Gli genes during cerebellum
      development.
AB  - The cerebellum consists of a highly organized set of folia that are largely
      generated postnatally during expansion of the granule cell precursor (GCP) pool.
      Since the secreted factor sonic hedgehog (Shh) is expressed in Purkinje cells and
      functions as a GCP mitogen in vitro, it is possible that Shh influences foliation
      during cerebellum development by regulating the position and/or size of lobes. We
      studied how Shh and its transcriptional mediators, the Gli proteins, regulate GCP
      proliferation in vivo, and tested whether they influence foliation. We
      demonstrate that Shh expression correlates spatially and temporally with
      foliation. Expression of the Shh target gene Gli1 is also highest in the anterior
      medial cerebellum, but is restricted to proliferating GCPs and Bergmann glia. By
      contrast, Gli2 is expressed uniformly in all cells in the developing cerebellum
      except Purkinje cells and Gli3 is broadly expressed along the anteroposterior
      axis. Whereas Gli mutants have a normal cerebellum, Gli2 mutants have greatly
      reduced foliation at birth and a decrease in GCPs. In a complementary study using
      transgenic mice, we show that overexpressing Shh in the normal domain does not
      grossly alter the basic foliation pattern, but does lead to prolonged
      proliferation of GCPs and an increase in the overall size of the cerebellum.
      Taken together, these studies demonstrate that positive Shh signaling through
      Gli2 is required to generate a sufficient number of GCPs for proper lobe growth.

PMID- 15496442
TI  - Eya1 and Six1 are essential for early steps of sensory neurogenesis in mammalian
      cranial placodes.
AB  - Eya1 encodes a transcriptional co-activator and is expressed in cranial sensory
      placodes. It interacts with and functions upstream of the homeobox gene Six1
      during otic placodal development. Here, we have examined their role in cranial
      sensory neurogenesis. Our data show that the initial cell fate determination for
      the vestibuloacoustic neurons and their delamination appeared to be unaffected in
      the absence of Eya1 or Six1 as judged by the expression of the basic helix-loop
      helix genes, Neurog1 that specifies the neuroblast cell lineage, and Neurod that
      controls neuronal differentiation and survival. However, both genes are necessary
      for normal maintenance of neurogenesis. During the development of epibranchial
      placode-derived distal cranial sensory ganglia, while the phenotype appears less
      severe in Six1 than in Eya1 mutants, an early arrest of neurogenesis was observed
      in the mutants. The mutant epibranchial progenitor cells fail to express Neurog2
      that is required for the determination of neuronal precursors, and other basic
      helix-loop-helix as well as the paired homeobox Phox2 genes that are essential
      for neural differentiation and maintenance. Failure to activate their normal
      differentiation program resulted in abnormal apoptosis of the progenitor cells.
      Furthermore, we show that disruption of viable ganglion formation leads to
      pathfinding errors of branchial motoneurons. Finally, our results suggest that
      the Eya-Six regulatory hierarchy also operates in the epibranchial placodal
      development. These findings uncover an essential function for Eya1 and Six1 as
      critical determination factors in acquiring both neuronal fate and neuronal
      subtype identity from epibranchial placodal progenitors. These analyses define a
      specific role for both genes in early differentiation and survival of the
      placodally derived cranial sensory neurons.

PMID- 15496443
TI  - Hes genes regulate size, shape and histogenesis of the nervous system by control
      of the timing of neural stem cell differentiation.
AB  - Radial glial cells derive from neuroepithelial cells, and both cell types are
      identified as neural stem cells. Neural stem cells are known to change their
      competency over time during development: they initially undergo self-renewal only
      and then give rise to neurons first and glial cells later. Maintenance of neural
      stem cells until late stages is thus believed to be essential for generation of
      cells in correct numbers and diverse types, but little is known about how the
      timing of cell differentiation is regulated and how its deregulation influences
      brain organogenesis. Here, we report that inactivation of Hes1 and Hes5, known
      Notch effectors, and additional inactivation of Hes3 extensively accelerate cell
      differentiation and cause a wide range of defects in brain formation. In Hes
      deficient embryos, initially formed neuroepithelial cells are not properly
      maintained, and radial glial cells are prematurely differentiated into neurons
      and depleted without generation of late-born cells. Furthermore, loss of radial
      glia disrupts the inner and outer barriers of the neural tube, disorganizing the
      histogenesis. In addition, the forebrain lacks the optic vesicles and the
      ganglionic eminences. Thus, Hes genes are essential for generation of brain
      structures of appropriate size, shape and cell arrangement by controlling the
      timing of cell differentiation. Our data also indicate that embryonic neural stem
      cells change their characters over time in the following order: Hes-independent
      neuroepithelial cells, transitory Hes-dependent neuroepithelial cells and Hes
      dependent radial glial cells.

PMID- 15496444
TI  - Caspase inhibition during apoptosis causes abnormal signalling and developmental
      aberrations in Drosophila.
AB  - Programmed cell death or apoptosis plays an important role in the development of
      multicellular organisms and can also be induced by various stress events. In the
      Drosophila wing imaginal disc there is little apoptosis in normal development but
      X-rays can induce high apoptotic levels, which eliminate a large fraction of the
      disc cells. Nevertheless, irradiated discs form adult patterns of normal size,
      indicating the existence of compensatory mechanisms. We have characterised the
      apoptotic response of the wing disc to X-rays and heat shock and also the
      developmental consequences of compromising apoptosis. We have used the caspase
      inhibitor P35 to prevent the death of apoptotic cells and found that it causes
      increased non-autonomous cell proliferation, invasion of compartments and
      persistent misexpression of the wingless (wg) and decapentaplegic (dpp)
      signalling genes. We propose that a feature of cells undergoing apoptosis is to
      activate wg and dpp, probably as part of the mechanism to compensate for cell
      loss. If apoptotic cells are not eliminated, they continuously emit Wg and Dpp
      signals, which results in developmental aberrations. We suggest that a similar
      process of uncoupling apoptosis initiation and cell death may occur during tumour
      formation in mammalian cells.

PMID- 15496446
TI  - Induction and autoregulation of the anti-proneural gene Bar during retinal
      neurogenesis in Drosophila.
AB  - Neurogenesis in Drosophila eye imaginal disc is controlled by interactions of
      positive and negative regulatory genes. The basic helix-loop-helix (bHLH)
      transcription factor Atonal (Ato) plays an essential proneural function in the
      morphogenetic furrow to induce the formation of R8 founder neurons. Bar
      homeodomain proteins are required for transcriptional repression of ato in the
      basal undifferentiated retinal precursor cells to prevent ectopic neurogenesis
      posterior to the furrow of the eye disc. Thus, precise regulation of Bar
      expression in the basal undifferentiated cells is crucial for neural patterning
      in the eye. We show evidence that Bar expression in the basal undifferentiated
      cells is regulated by at least three different pathways, depending on the
      developmental time and the position in the eye disc. First, at the time of furrow
      initiation, Bar expression is induced independent of Ato by Hedgehog (Hh)
      signaling from the posterior margin of the disc. Second, during furrow
      progression, Bar expression is also induced by Ato-dependent EGFR (epidermal
      growth factor receptor) signaling from the migrating furrow. Finally, once
      initiated, Bar expression can be maintained by positive autoregulation.
      Therefore, we propose that the domain of Bar expression for Ato repression is
      established and maintained by a combination of non autonomous Hh/EGFR signaling
      pathways and autoregulation of Bar.

PMID- 15496447
TI  - Modulation of Erbb2 signaling during development: a threshold level of Erbb2
      signaling is required for development.
AB  - We have generated a series of Erbb2 cDNA knock-in animals to explore the role of
      signaling pathways coupled to Erbb2 during development. Although this knock-in
      allele was hypomorphic, expressing tenfold less Erbb2 protein than wild type, the
      knock-in animals were healthy. However, a further twofold reduction in Erbb2
      levels in hemizygous knock-in animals resulted in perinatal lethality with
      defects in the innervation of the diaphragm. Genetic rescue of this hypomorph was
      accomplished by expression of the Erbb2-Y1028F mutant in a comparable knock-in
      allele. Interestingly, hemizygous Y1028F animals were viable with normal
      innervation of the diaphragm. Molecular analyses revealed that the Y1028F allele
      expressed higher levels of Erbb2 and that Y1028 promoted the turnover of the
      receptor. In addition, ablation of the Shc-binding site in Erbb2 (Y1227) resulted
      in subtle defects in the sensory nerves not observed in the other mutant erbb2
      strains. Thus, we have established how Erbb2 levels may be modulated through
      development and that a minimum threshold level of Erbb2 is required.

PMID- 15496445
TI  - Neural crest stem cells undergo multilineage differentiation in developing
      peripheral nerves to generate endoneurial fibroblasts in addition to Schwann
      cells.
AB  - Neural crest stem cells (NCSCs) persist in peripheral nerves throughout late
      gestation but their function is unknown. Current models of nerve development only
      consider the generation of Schwann cells from neural crest, but the presence of
      NCSCs raises the possibility of multilineage differentiation. We performed Cre
      recombinase fate mapping to determine which nerve cells are neural crest derived.
      Endoneurial fibroblasts, in addition to myelinating and non-myelinating Schwann
      cells, were neural crest derived, whereas perineurial cells, pericytes and
      endothelial cells were not. This identified endoneurial fibroblasts as a novel
      neural crest derivative, and demonstrated that trunk neural crest does give rise
      to fibroblasts in vivo, consistent with previous studies of trunk NCSCs in
      culture. The multilineage differentiation of NCSCs into glial and non-glial
      derivatives in the developing nerve appears to be regulated by neuregulin, notch
      ligands, and bone morphogenic proteins, as these factors are expressed in the
      developing nerve, and cause nerve NCSCs to generate Schwann cells and
      fibroblasts, but not neurons, in culture. Nerve development is thus more complex
      than was previously thought, involving NCSC self-renewal, lineage commitment and
      multilineage differentiation.

PMID- 15496448
TI  - Elucidating the protective and pathologic T cell species in the virus-induced
      corneal immunoinflammatory condition herpetic stromal keratitis.
AB  - Herpetic stromal keratitis (HSK) results in postinfection with Herpes simplex
      virus type 1 (HSV-1). The pathogenesis involves tissue damage by the host immune
      system, classifying HSK as an immunopathological disease. The crucial disease
      orchestrating cells is thought to be the T lymphocytes. The present study
      elucidates pathogenic and protective T cell subsets involved in the development
      of HSK using the gBT mice, which possess a monoclonal population of CD8+ T cells
      reactive to a HSV immunodominant epitope. Results show that HSV-reactive CD8+ T
      cells enter infected corneas during the acute but not the chronic phase of the
      disease during which the predominant population is CD4+ T cells. Adoptive
      transfer experiments in T and B cell-deficient recombination-activating gene
      knockout mice revealed that HSV-reactive CD8+ T cells are capable of ocular virus
      clearance, possibly through a combination of corneal and peripheral nervous
      system antiviral effects, but are not involved in lesion development. CD4+ T
      cells of the virus-specific or nonspecific species emerged as the pathogenic T
      cells capable of precipitating disease. These observations have the potential to
      yield important treatment strategies by targeting specific cell types in HSK.

PMID- 15496449
TI  - JAK2 is necessary and sufficient for interferon-gamma-induced transcription of
      the gene encoding gp91PHOX.
AB  - During the inflammatory response, interferon-gamma (IFN-gamma) increases
      transcription of the gene encoding gp91PHOX, a respiratory burst oxidase
      component. This gene (referred to as the CYBB gene) is transcribed in phagocytic
      cells differentiated beyond the promyelocyte stage, and transcription continues
      until cell death. Previous investigations identified a positive regulatory
      element in the proximal CYBB promoter referred to as the hematopoiesis-associated
      factor 1 (HAF1)-cis element. This element is activated by a multiprotein complex,
      which includes the IFN consensus sequence-binding protein (ICSBP). Interaction of
      this complex with the HAF1-cis element requires ICSBP tyrosine phosphorylation,
      which is induced by IFN-gamma stimulation of phagocytic cells. Previous studies
      also identified a negative cis element in the CYBB promoter. This element is
      repressed by the homeodomain protein HoxA10. HoxA10 tyrosine phosphorylation,
      which occurs in response to IFN-gamma, decreases HoxA10 DNA binding and therefore
      repression of CYBB transcription. In these studies, we determine Janus tyrosine
      kinase 2 (JAK2) activation is necessary and sufficient for IFN-gamma-induced CYBB
      transcription in phagocytic cells and also for ICSBP and HoxA10 tyrosine
      phosphorylation. Consistent with these results, we find JAK2 activation is
      sufficient to induce ICSBP interaction with the HAF1 element and abolish HoxA10
      binding to the CYBBrepressor element. Therefore, these findings provide direct
      demonstration of JAK2 dependence of IFN-gamma-induced CYBB transcription. In
      addition, these results identify a mechanism mediating this effect.

PMID- 15496450
TI  - Linking the "two-hit" response following injury to enhanced TLR4 reactivity.
AB  - Severe injury can initiate an exaggerated systemic inflammatory response and
      multiple organ failure (MOF) if a subsequent immune stimulus, "second hit",
      occurs. Using a mouse thermal injury model, we tested whether changes in innate
      immune cell reactivity following injury can contribute to the development of
      heightened inflammation and MOF. Using high-purity Escherichia coli
      lipopolysaccharide (LPS) to selectively stimulate Toll-like receptor 4 (TLR4), we
      demonstrate augmented interleukin (IL)-1beta, tumor necrosis factor alpha (TNF
      alpha), and IL-6 production by 1 day but particularly, at 7 days after injury.
      The in vivo significance of enhanced TLR4 responsiveness was explored by
      challenging sham or burn mice with LPS at 1 or 7 days after injury and
      determining mortality along with in vivo cytokine and chemokine levels. Mortality
      was high (75%) in LPS-challenged burn but not sham mice at 7 days, although not
      at 1 day, after injury. Death was associated with leukocyte sequestration in the
      lungs and livers along with increased proinflammatory cytokine and chemokine
      levels in these organs. Blocking TNF-alpha activity prevented this mortality,
      suggesting that excessive TNF-alpha production contributes to this lethal
      response. These findings demonstrate the potential lethality of excessive TLR4
      reactivity after injury and provide an explanation for the exaggerated
      inflammatory response to a second hit, which can occur following severe injury.

PMID- 15496451
TI  - Macrophage activation by a DNA/cationic liposome complex requires endosomal
      acidification and TLR9-dependent and -independent pathways.
AB  - Previously, we showed that bacterial DNA and vertebrate DNA/cationic liposome
      complexes stimulate potent inflammatory responses in cultured mouse macrophages.
      In the present study, we examined whether endocytosis and subsequent
      acidification are associated with these responses. The endocytosis inhibitor,
      cytochalasin B, reduced tumor necrosis factor alpha (TNF-alpha) production by a
      plasmid DNA (pDNA)/cationic liposome complex. The endosomal acidification
      inhibitor, monensin, inhibited cytokine production by pDNA or a calf thymus
      DNA/liposome complex. These results suggest, similarly to CpG motif-dependent
      responses, that endocytosis and subsequent endosomal acidification are also
      required for these inflammatory responses. It is intriguing that another
      inhibitor of endosomal acidification, bafilomycin A, stimulated the production of
      TNF-alpha mRNA and its protein after removal of the pDNA/liposome complex and
      inhibitors, although it inhibited the release of interleukin-6. Similar phenomena
      were observed in the activation of macrophages by CpG oligodeoxynucleotide, calf
      thymus DNA, and Escherichia coli DNA complexed with liposomes. Moreover,
      bafilomycin A also induced a high degree of TNF-alpha release after stimulation
      with naked pDNA. These results suggest that bafilomycin A increases TNF-alpha
      production induced by DNA at the transcriptional level via an as-yet unknown
      mechanism. Furthermore, we investigated the contribution of Toll-like receptor 9
      (TLR9), the receptor of CpG motifs, to the cell activation by the DNA/cationic
      liposome complex using the macrophages from TLR9-/- mice. We observed a reduced
      inflammatory cytokine release from macrophages of TLR9-/- mice compared with wild
      type mice. However, the cytokine production was not completely abolished,
      suggesting that the DNA/cationic liposome complex can induce macrophage
      activation via TLR9-dependent and -independent pathways.

PMID- 15496452
TI  - Proteomic analysis of the Arabidopsis nucleolus suggests novel nucleolar
      functions.
AB  - The eukaryotic nucleolus is involved in ribosome biogenesis and a wide range of
      other RNA metabolism and cellular functions. An important step in the functional
      analysis of the nucleolus is to determine the complement of proteins of this
      nuclear compartment. Here, we describe the first proteomic analysis of plant
      (Arabidopsis thaliana) nucleoli, in which we have identified 217 proteins. This
      allows a direct comparison of the proteomes of an important nuclear structure
      between two widely divergent species: human and Arabidopsis. The comparison
      identified many common proteins, plant-specific proteins, proteins of unknown
      function found in both proteomes, and proteins that were nucleolar in plants but
      nonnucleolar in human. Seventy-two proteins were expressed as GFP fusions and 87%
      showed nucleolar or nucleolar-associated localization. In a striking and
      unexpected finding, we have identified six components of the postsplicing exon
      junction complex (EJC) involved in mRNA export and nonsense-mediated decay
      (NMD)/mRNA surveillance. This association was confirmed by GFP-fusion protein
      localization. These results raise the possibility that in plants, nucleoli may
      have additional functions in mRNA export or surveillance.

PMID- 15496453
TI  - Mammalian protein SCP1 forms synaptonemal complex-like structures in the absence
      of meiotic chromosomes.
AB  - Synaptonemal complexes (SCs) are evolutionary conserved, meiosis-specific
      structures that play a central role in synapsis of homologous chromosomes,
      chiasmata distribution, and chromosome segregation. However, it is still for the
      most part unclear how SCs do assemble during meiotic prophase. Major components
      of mammalian SCs are the meiosis-specific proteins SCP1, 2, and 3. To investigate
      the role of SCP1 in SC assembly, we expressed SCP1 in a heterologous system,
      i.e., in COS-7 cells that normally do not express SC proteins. Notably, under
      these experimental conditions SCP1 is able to form structures that closely
      resemble SCs (i.e., polycomplexes). Moreover, we show that mutations that modify
      the length of the central alpha-helical domain of SCP1 influence the width of
      polycomplexes. Finally, we demonstrate that deletions of the nonhelical N- or C
      termini both affect polycomplex assembly, although in a different manner. We
      conclude that SCP1 is a primary determinant of SC assembly that plays a key role
      in synapsis of homologous chromosomes.

PMID- 15496454
TI  - Anillin binds nonmuscle myosin II and regulates the contractile ring.
AB  - We demonstrate that the contractile ring protein anillin interacts directly with
      nonmuscle myosin II and that this interaction is regulated by myosin light chain
      phosphorylation. We show that despite their interaction, anillin and myosin II
      are independently targeted to the contractile ring. Depletion of anillin in
      Drosophila or human cultured cells results in cytokinesis failure. Human cells
      depleted for anillin fail to properly regulate contraction by myosin II late in
      cytokinesis and fail in abscission. We propose a role for anillin in spatially
      regulating the contractile activity of myosin II during cytokinesis.

PMID- 15496455
TI  - FAT/CD36-mediated long-chain fatty acid uptake in adipocytes requires plasma
      membrane rafts.
AB  - We previously reported that lipid rafts are involved in long-chain fatty acid
      (LCFA) uptake in 3T3-L1 adipocytes. The present data show that LCFA uptake does
      not depend on caveolae endocytosis because expression of a dominant negative
      mutant of dynamin had no effect on uptake of [3H]oleic acid, whereas it
      effectively prevented endocytosis of cholera toxin. Isolation of detergent
      resistant membranes (DRMs) from 3T3-L1 cell homogenates revealed that FAT/CD36
      was expressed in both DRMs and detergent-soluble membranes (DSMs), whereas FATP1
      and FATP4 were present only in DSMs but not DRMs. Disruption of lipid rafts by
      cyclodextrin and specific inhibition of FAT/CD36 by sulfo-N-succinimidyl oleate
      (SSO) significantly decreased uptake of [3H]oleic acid, but simultaneous
      treatment had no additional or synergistic effects, suggesting that both
      treatments target the same mechanism. Indeed, subcellular fractionation
      demonstrated that plasma membrane fatty acid translocase (FAT/CD36) is
      exclusively located in lipid rafts, whereas intracellular FAT/CD36 cofractionated
      with DSMs. Binding assays confirmed that [3H]SSO predominantly binds to FAT/CD36
      within plasma membrane DRMs. In conclusion, our data strongly suggest that
      FAT/CD36 mediates raft-dependent LCFA uptake. Plasma membrane lipid rafts might
      control LCFA uptake by regulating surface availability of FAT/CD36.

PMID- 15496456
TI  - Flagellar length control system: testing a simple model based on intraflagellar
      transport and turnover.
AB  - Flagellar length regulation provides a simple model system for addressing the
      general problem of organelle size control. Based on a systems-level analysis of
      flagellar dynamics, we have proposed a mechanism for flagellar length control in
      which length is set by the balance of continuous flagellar assembly and
      disassembly. The model proposes that the assembly rate is length dependent due to
      the inherent length dependence of intraflagellar transport, whereas disassembly
      is length independent, such that the two rates can only reach a balance point at
      a single length. In this report, we test this theoretical model by using three
      different measurements: 1) the quantity of intraflagellar transport machinery as
      a function of length, 2) the variation of flagellar length as a function of
      flagellar number, and 3) the rate of flagellar growth as a function of length. We
      find that the quantity of intraflagellar transport machinery is independent of
      length, that flagellar length is a decreasing function of flagellar number, and
      that flagellar growth rate in regenerating flagella depends on length and not on
      the time since regeneration began. These results are consistent with the balance
      point model for length control. The three strategies used here are not limited to
      flagella and can in principle be adapted to probe size control systems for any
      organelle.

PMID- 15496457
TI  - Normal biogenesis and cycling of empty synaptic vesicles in dopamine neurons of
      vesicular monoamine transporter 2 knockout mice.
AB  - The neuronal isoform of vesicular monoamine transporter, VMAT2, is responsible
      for packaging dopamine and other monoamines into synaptic vesicles and thereby
      plays an essential role in dopamine neurotransmission. Dopamine neurons in mice
      lacking VMAT2 are unable to store or release dopamine from their synaptic
      vesicles. To determine how VMAT2-mediated filling influences synaptic vesicle
      morphology and function, we examined dopamine terminals from VMAT2 knockout mice.
      In contrast to the abnormalities reported in glutamatergic terminals of mice
      lacking VGLUT1, the corresponding vesicular transporter for glutamate, we found
      that the ultrastructure of dopamine terminals and synaptic vesicles in VMAT2
      knockout mice were indistinguishable from wild type. Using the activity-dependent
      dyes FM1-43 and FM2-10, we also found that synaptic vesicles in dopamine neurons
      lacking VMAT2 undergo endocytosis and exocytosis with kinetics identical to those
      seen in wild-type neurons. Together, these results demonstrate that dopamine
      synaptic vesicle biogenesis and cycling are independent of vesicle filling with
      transmitter. By demonstrating that such empty synaptic vesicles can cycle at the
      nerve terminal, our study suggests that physiological changes in VMAT2 levels or
      trafficking at the synapse may regulate dopamine release by altering the ratio of
      fillable-to-empty synaptic vesicles, as both continue to cycle in response to
      neural activity.

PMID- 15496458
TI  - Palmitoylation-dependent estrogen receptor alpha membrane localization:
      regulation by 17beta-estradiol.
AB  - A fraction of the nuclear estrogen receptor alpha (ERalpha) is localized to the
      plasma membrane region of 17beta-estradiol (E2) target cells. We previously
      reported that ERalpha is a palmitoylated protein. To gain insight into the
      molecular mechanism of ERalpha residence at the plasma membrane, we tested both
      the role of palmitoylation and the impact of E2 stimulation on ERalpha membrane
      localization. The cancer cell lines expressing transfected or endogenous human
      ERalpha (HeLa and HepG2, respectively) or the ERalpha nonpalmitoylable Cys447Ala
      mutant transfected in HeLa cells were used as experimental models. We found that
      palmitoylation of ERalpha enacts ERalpha association with the plasma membrane,
      interaction with the membrane protein caveolin-1, and nongenomic activities,
      including activation of signaling pathways and cell proliferation (i.e., ERK and
      AKT activation, cyclin D1 promoter activity, DNA synthesis). Moreover, E2 reduces
      both ERalpha palmitoylation and its interaction with caveolin-1, in a time- and
      dose-dependent manner. These data point to the physiological role of ERalpha
      palmitoylation in the receptor localization to the cell membrane and in the
      regulation of the E2-induced cell proliferation.

PMID- 15496459
TI  - The efficiency of protein compartmentalization into the secretory pathway.
AB  - Numerous proteins targeted for the secretory pathway are increasingly implicated
      in functional or pathological roles at alternative cellular destinations. The
      parameters that allow secretory or membrane proteins to reside in intracellular
      locales outside the secretory pathway remain largely unexplored. In this study,
      we have used an extremely sensitive and quantitative assay to measure the in vivo
      efficiency of signal sequence-mediated protein segregation into the secretory
      pathway. Our findings reveal that segregation efficiency varies tremendously
      among signals, ranging from >95 to <60%. The nonsegregated fraction is generated
      by a combination of mechanisms that includes inefficient signal-mediated
      translocation into the endoplasmic reticulum and leaky ribosomal scanning. The
      segregation efficiency of some, but not other signal sequences, could be
      influenced in cis by residues in the mature domain or in trans by yet
      unidentified cellular factors. These findings imply that protein
      compartmentalization can be modulated in a substrate-specific manner to generate
      biologically significant quantities of cytosolically available secretory and
      membrane proteins.

PMID- 15496460
TI  - NGF controls dendrite development in hippocampal neurons by binding to p75NTR and
      modulating the cellular targets of Notch.
AB  - Notch and neurotrophins control neuronal shape, but it is not known whether their
      signaling pathways intersect. Here we report results from hippocampal neuronal
      cultures that are in support of this possibility. We found that low cell density
      or blockade of Notch signaling by a soluble Delta-Fc ligand decreased the mRNA
      levels of the nuclear targets of Notch, the homologues of enhancer-of-split 1 and
      5 (Hes1/5). This effect was associated with enhanced sprouting of new dendrites
      or dendrite branches. In contrast, high cell density or exposure of low-density
      cultures to NGF increased the Hes1/5 mRNA, reduced the number of primary
      dendrites and promoted dendrite elongation. The NGF effects on both Hes1/5
      expression and dendrite morphology were prevented by p75-antibody (a p75NTR
      blocking antibody) or transfection with enhancer-of-split 6 (Hes6), a condition
      known to suppress Hes activity. Nuclear translocation of NF-kappaB was identified
      as a link between p75NTR and Hes1/5 because it was required for the up-regulation
      of these two genes. The convergence of the Notch and p75NTR signaling pathways at
      the level of Hes1/5 illuminates an unexpected mechanism through which a
      diffusible factor (NGF) could regulate dendrite growth when cell-cell interaction
      via Notch is not in action.

PMID- 15496461
TI  - An unusual and overlooked complication of nasogastric tube feeding.
AB  - Rechecking the position of the nasogastric tube after oropharyngeal suction is
      not common practice. Our patient deteriorated after oropharyngeal suction was
      performed, whilst nasogastric feeding continued. We suggest that nasogastric
      feeding should be stopped during oropharyngeal suction and the tube position
      should be checked every time an oropharyngeal suction is performed.

PMID- 15496462
TI  - Older people's use of Accident and Emergency services.
AB  - INTRODUCTION: It has previously been reported that patients aged over 65 years
      account for 15% of Accident and Emergency (A&E) attendances. Despite this, there
      have been few studies looking at older people's use of A&E. This study describes
      the A&E attendance patterns of older people, defined as those aged 65 years and
      over, using data from an NHS region over a number of years. Their attendances are
      also compared with those of the rest of the population. DATA AND METHODS: A&E
      attendance data were collected for 14 Acute Trusts in the West Midlands for the
      period from 1 April 1999 to 31 March 2002 via the West Midlands Accident and
      Emergency Surveillance Centre. RESULTS: Patients aged 65 years and over accounted
      for 18% of all attendances. Attendance rates were highest in those aged over 80
      years. Older patients were significantly more likely to attend during the morning
      and early afternoon, during the winter months, arrive by ambulance and require
      admission to hospital. Older patients were significantly more likely to attend
      with non-injury, particularly cardiac-related conditions. Injuries accounted for
      33.1% of attendances in the over-65s compared with 59.9% in the 0-64s.
      CONCLUSIONS: This study is the first in England to look at the A&E attendance
      patterns of all older people in an NHS region. It has demonstrated the continued
      high level use of A&E by those aged over 65 years. This highlights the need for
      continued systemic monitoring of A&E attendance patterns to enable planners to
      accommodate the impact of the increasingly ageing population.

PMID- 15496463
TI  - Capacity and coercion: dilemmas in the discharge of older people with dementia
      from general hospital settings.
AB  - Discharge planning of older people with dementia can present difficult ethical
      dilemmas to the general hospital clinician. These difficulties may be
      particularly pronounced for those who are moderately severely affected and for
      whom hazards are anticipated on discharge home. In many cases the wishes of the
      individual to return home may differ markedly from those of health care
      professionals, carers or relatives. In order to reduce these tensions and
      preserve the choice of the individual as far as possible, we try to put into
      context a number of different issues. We discuss some of the misconceptions
      regarding the legal powers available in these situations, the limited and
      sometimes confusing issue of capacity and the role of Community Mental Health
      Teams in preserving autonomy and independence of older people with dementia in
      their own homes.

PMID- 15496464
TI  - A biochemical oscillator explains several aspects of Myxococcus xanthus behavior
      during development.
AB  - During development, Myxococcus xanthus cells produce a series of spatial patterns
      by coordinating their motion through a contact-dependent signal, the C-signal. C
      signaling modulates the frequency at which cells reverse their gliding direction.
      It does this by interacting with the Frz system (a homolog of the Escherichia
      coli chemosensory system) via a cascade of covalent modifications. Here we show
      that introducing a negative feedback into this cascade results in oscillatory
      behavior of the signaling circuit. The model explains several aspects of M.
      xanthus behavior during development, including the nonrandom distribution of
      reversal times, and the differences in response of the reversal frequency to both
      moderate and high levels of C-signaling at different developmental stages. We
      also propose experiments to test the model.

PMID- 15496465
TI  - Formation of an actin-like filament concurrent with the enzymatic synthesis of
      inorganic polyphosphate.
AB  - Inorganic polyphosphate (poly P), a chain of hundreds of phosphate residues
      linked by ATP-like bonds, is found in every cell in nature and is commonly
      produced from ATP by poly P kinases (e.g., PPK1). Dictyostelium discoideum, the
      social slime mold, possesses a PPK activity (DdPPK1) with sequence similarity to
      bacterial PPKs. We find here a previously unrecognized PPK (DdPPK2) in D.
      discoideum with the sequences and properties of actin-related proteins (Arps)
      that are similar to muscle actins in size, properties, and globular-filamentous
      structural transitions. Significantly, the unique actin inhibitors, phalloidin
      and DNase I, also inhibit synthesis of poly P by DdPPK2. Thus, this particular
      Arp complex is an enzyme that can polymerize into an actin-like filament
      concurrent with its synthesis of a poly P chain in a fully reversible reaction.

PMID- 15496466
TI  - Total synthesis of long DNA sequences: synthesis of a contiguous 32-kb polyketide
      synthase gene cluster.
AB  - To exploit the huge potential of whole-genome sequence information, the ability
      to efficiently synthesize long, accurate DNA sequences is becoming increasingly
      important. An approach proposed toward this end involves the synthesis of
      approximately 5-kb segments of DNA, followed by their assembly into longer
      sequences by conventional cloning methods [Smith, H. O., Hutchinson, C. A., III,
      Pfannkoch, C. & Venter, J. C. (2003) Proc. Natl. Acad. Sci. USA 100, 15440
      15445]. The major current impediment to the success of this tactic is the
      difficulty of building the approximately 5-kb components accurately, efficiently,
      and rapidly from short synthetic oligonucleotide building blocks. We have
      developed and implemented a strategy for the high-throughput synthesis of long,
      accurate DNA sequences. Unpurified 40-base synthetic oligonucleotides are built
      into 500- to 800-bp "synthons" with low error frequency by automated PCR-based
      gene synthesis. By parallel processing, these synthons are efficiently joined
      into multisynthon approximately 5-kb segments by using only three endonucleases
      and "ligation by selection." These large segments can be subsequently assembled
      into very long sequences by conventional cloning. We validated the approach by
      building a synthetic 31,656-bp polyketide synthase gene cluster whose
      functionality was demonstrated by its ability to produce the megaenzyme and its
      polyketide product in Escherichia coli.

PMID- 15496467
TI  - A single active site residue directs oxygenation stereospecificity in
      lipoxygenases: stereocontrol is linked to the position of oxygenation.
AB  - Lipoxygenases are a class of dioxygenases that form hydroperoxy fatty acids with
      distinct positional and stereo configurations. Several amino acid residues
      influencing regiospecificity have been identified, whereas the basis of
      stereocontrol is not understood. We have now identified a single residue in the
      lipoxygenase catalytic domain that is important for stereocontrol; it is
      conserved as an Ala in S lipoxygenases and a Gly in R lipoxygenases. Our results
      with mutation of the conserved Ala to Gly in two S lipoxygenases (mouse 8S-LOX
      and human 15-LOX-2) and the corresponding Gly-Ala substitution in two R
      lipoxygenases (human 12R-LOX and coral 8R-LOX) reveal that the basis for R or S
      stereo-control also involves a switch in the position of oxygenation on the
      substrate. After the initial hydrogen abstraction, antarafacial oxygenation at
      one end or the other of the activated pair of double bonds (pentadiene) gives,
      for example, 8S or 12R product. The Ala residue promotes oxygenation on the
      reactive pentadiene at the end deep in the substrate binding pocket and S
      stereochemistry of the product hydroperoxide, and a Gly residue promotes
      oxygenation at the proximal end of the reactive pentadiene resulting in R
      stereochemistry. A model of lipoxygenase reaction specificity is proposed in
      which product regiochemistry and stereochemistry are determined by fixed
      relationships between substrate orientation, hydrogen abstraction, and the Gly or
      Ala residue we have identified.

PMID- 15496468
TI  - Combining biological networks to predict genetic interactions.
AB  - Genetic interactions define overlapping functions and compensatory pathways. In
      particular, synthetic sick or lethal (SSL) genetic interactions are important for
      understanding how an organism tolerates random mutation, i.e., genetic
      robustness. Comprehensive identification of SSL relationships remains far from
      complete in any organism, because mapping these networks is highly labor
      intensive. The ability to predict SSL interactions, however, could efficiently
      guide further SSL discovery. Toward this end, we predicted pairs of SSL genes in
      Saccharomyces cerevisiae by using probabilistic decision trees to integrate
      multiple types of data, including localization, mRNA expression, physical
      interaction, protein function, and characteristics of network topology.
      Experimental evidence demonstrated the reliability of this strategy, which, when
      extended to human SSL interactions, may prove valuable in discovering drug
      targets for cancer therapy and in identifying genes responsible for multigenic
      diseases.

PMID- 15496469
TI  - The Ets-1 transcription factor is required for complete pre-T cell receptor
      function and allelic exclusion at the T cell receptor beta locus.
AB  - The pre-T cell receptor (TCR) functions as a critical checkpoint during alphabeta
      T cell development. Signaling through the pre-TCR controls the differentiation of
      immature CD4(-)CD8(-)CD25(+)CD44(-) [double-negative (DN)3] thymocytes into
      CD4(+)CD8(+) double-positive (DP) cells through the CD4(-)CD8(-)CD25(-)CD44(
      )(DN4) stage. In addition, pre-TCR activity triggers expansion and survival of
      thymocytes and inhibits TCRbeta gene rearrangement through a process referred to
      as allelic exclusion. Whereas many proteins involved in the pre-TCR transduction
      cascade have been identified, little is known about the nuclear factors
      associated with receptor function. Here, we use gene targeting to inactivate the
      Ets-1 transcription factor in mice and analyze pre-TCR function in developing Ets
      1-deficient (Ets-1(-/-)) thymocytes. We find that inactivation of Ets-1 impairs
      the development of DN3 into DP thymocytes and induces an elevated rate of cell
      death in the DN4 subset. This defect appears specific to the alphabeta lineage
      because gammadelta T cells maturate efficiently. Finally, the percentage of
      thymocytes coexpressing two different TCRbeta chains is increased in the Ets-1(-/
      ) background and, in contrast with wild type, forced activation of pre-TCR
      signaling does not block endogenous TCRbeta gene rearrangement. These data
      identify Ets-1 as a critical transcription factor for pre-TCR functioning and for
      allelic exclusion at the TCRbeta locus.

PMID- 15496470
TI  - Resolution of the novel immune-type receptor gene cluster in zebrafish.
AB  - The novel immune-type receptor (NITR) genes encode a unique multigene family of
      leukocyte regulatory receptors, which possess an extracellular Ig variable (V)
      domain and may function in innate immunity. Artificial chromosomes that encode
      zebrafish NITRs have been assembled into a contig spanning approximately 350 kb.
      Resolution of the complete NITR gene cluster has led to the identification of
      eight previously undescribed families of NITRs and has revealed the presence of C
      type lectins within the locus. A maximum haplotype of 36 NITR genes (138 gene
      sequences in total) can be grouped into 12 distinct families, including
      inhibitory and activating receptors. An extreme level of interindividual
      heterozygosity is reflected in allelic polymorphisms, haplotype variation, and
      family-specific isoform complexity. In addition, the exceptional diversity of
      NITR sequences among species suggests divergent evolution of this multigene
      family with a birth-and-death process of member genes. High-confidence modeling
      of Nitr V-domain structures reveals a significant shift in the spatial
      orientation of the Ig fold, in the region of highest interfamily variation,
      compared with Ig V domains. These studies resolve a complete immune gene cluster
      in zebrafish and indicate that the NITRs represent the most complex family of
      activating/inhibitory surface receptors thus far described.

PMID- 15496471
TI  - Carbohydrate response element binding protein directly promotes lipogenic enzyme
      gene transcription.
AB  - Carbohydrate response element (ChRE)-binding protein (ChREBP) is a recently
      discovered transcription factor that is activated in response to high glucose
      concentrations in liver independently of insulin. ChREBP was first identified by
      its ability to bind the ChRE of the liver pyruvate kinase (LPK) gene. We recently
      reported that the increase in expression of multiple liver lipogenic enzyme mRNAs
      elicited by feeding a high-carbohydrate diet as well as that of LPK mRNA is
      markedly reduced in mice lacking ChREBP gene expression (ChREBP(-/-)) in
      comparison to WT mice. The present study provides evidence for a direct and
      dominant role of ChREBP in the glucose regulation of two key liver lipogenic
      enzymes, acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). ACC, FAS,
      and LPK mRNA levels were higher in WT hepatocytes cultured with high (25 mM)
      rather than low (5.5 mM) glucose medium, but there was no effect of glucose
      concentration on these mRNA levels in ChREBP(-/-) hepatocytes. Similarly,
      reporter constructs containing ACC, FAS, or LPK gene ChREs were responsive to
      glucose when transfected into WT but not ChREBP(-/-) hepatocytes, and glucose
      transactivation of the constructs in ChREBP(-/-) hepatocytes was restored by
      cotransfection with a ChREBP expression plasmid. ChREBP binding to ACC, FAS, and
      LPK ChRE sequences in vitro was demonstrated by electrophoretic mobility super
      shift assays. In vivo binding of ChREBP to ACC, FAS, and LPK gene promoters in
      intact liver nuclei from rats fed a high-carbohydrate diet was demonstrated by
      using a formaldehyde crosslinking and chromatin immunoprecipitation procedure.

PMID- 15496472
TI  - Modulation of dendritic differentiation by corticotropin-releasing factor in the
      developing hippocampus.
AB  - The interplay of environmental and genetic factors in the developmental
      organization of the hippocampus has not been fully elucidated. The neuropeptide
      corticotropin-releasing factor (CRF) is released from hippocampal interneurons by
      environmental signals, including stress, to increase synaptic efficacy. In the
      early postnatal hippocampus, we have previously characterized a transient
      population of CRF-expressing Cajal-Retzius-like cells. Here we queried whether
      this stress-activated neuromodulator influences connectivity in the developing
      hippocampal network. Using mice deficient in the principal hippocampal CRF
      receptor [CRF(1)(-/-)] and organotypic cultures grown in the presence of
      synthetic CRF, or CRF receptor antagonists, we found robust effects of CRF on
      dendritic differentiation in hippocampal neurons. In CRF(1)(-/-) mice, the
      dendritic trees of hippocampal principal cells were exuberant, an effect that was
      induced in normal hippocampi in vitro by the presence of CRF(1) antagonists. In
      both cases, total dendritic length and dendritic branching were significantly
      increased. In contrast, exogenous synthetic CRF blunted the dendritic growth in
      hippocampal organotypic cultures. Taken together, these findings suggest that
      endogenous CRF, if released excessively by previous early postnatal stress, might
      influence neuronal connectivity and thus function of the immature hippocampus.

PMID- 15496473
TI  - Crystal structure of 4-hydroxybutyryl-CoA dehydratase: radical catalysis
      involving a [4Fe-4S] cluster and flavin.
AB  - Dehydratases catalyze the breakage of a carbon-oxygen bond leading to unsaturated
      products via the elimination of water. The 1.6-A resolution crystal structure of
      4-hydroxybutyryl-CoA dehydratase from the gamma-aminobutyrate-fermenting
      Clostridium aminobutyricum represents a new class of dehydratases with an
      unprecedented active site architecture. A [4Fe-4S](2+) cluster, coordinated by
      three cysteine and one histidine residues, is located 7 A from the Re-side of a
      flavin adenine dinucleotide (FAD) moiety. The structure provides insight into the
      function of these ubiquitous prosthetic groups in the chemically nonfacile,
      radical-mediated dehydration of 4-hydroxybutyryl-CoA. The substrate can be bound
      between the [4Fe-4S](2+) cluster and the FAD with both cofactors contributing to
      its radical activation and catalytic conversion. Our results raise interesting
      questions regarding the mechanism of acyl-CoA dehydrogenases, which are involved
      in fatty acid oxidation, and address the divergent evolution of the ancestral
      common gene.

PMID- 15496474
TI  - CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus.
AB  - Angiotensin-converting enzyme 2 (ACE2) is a receptor for SARS-CoV, the novel
      coronavirus that causes severe acute respiratory syndrome [Li, W. Moore, M. J.,
      Vasilieva, N., Sui, J., Wong, S. K., Berne, M. A., Somasundaran, M., Sullivan, J.
      L., Luzuriaga, K., Greenough, T. C., et al. (2003) Nature 426, 450-454]. We have
      identified a different human cellular glycoprotein that can serve as an
      alternative receptor for SARS-CoV. A human lung cDNA library in vesicular
      stomatitis virus G pseudotyped retrovirus was transduced into Chinese hamster
      ovary cells, and the cells were sorted for binding of soluble SARS-CoV spike (S)
      glycoproteins, S(590) and S(1180). Clones of transduced cells that bound SARS-CoV
      S glycoprotein were inoculated with SARS-CoV, and increases in subgenomic viral
      RNA from 1-16 h or more were detected by multiplex RT-PCR in four cloned cell
      lines. Sequencing of the human lung cDNA inserts showed that each of the cloned
      cell lines contained cDNA that encoded human CD209L, a C-type lectin (also called
      L-SIGN). When the cDNA encoding CD209L from clone 2.27 was cloned and transfected
      into Chinese hamster ovary cells, the cells expressed human CD209L glycoprotein
      and became susceptible to infection with SARS-CoV. Immunohistochemistry showed
      that CD209L is expressed in human lung in type II alveolar cells and endothelial
      cells, both potential targets for SARS-CoV. Several other enveloped viruses
      including Ebola and Sindbis also use CD209L as a portal of entry, and HIV and
      hepatitis C virus can bind to CD209L on cell membranes but do not use it to
      mediate virus entry. Our data suggest that the large S glycoprotein of SARS-CoV
      may use both ACE2 and CD209L in virus infection and pathogenesis.

PMID- 15496475
TI  - Transcriptional targets of DAF-16 insulin signaling pathway protect C. elegans
      from extreme hypertonic stress.
AB  - All cells adapt to hypertonic stress by regulating their volume after shrinkage,
      by accumulating organic osmolytes, and by activating mechanisms that protect
      against and repair hypertonicity-induced damage. In mammals and nematodes,
      inhibition of signaling from the DAF-2/IGF-1 insulin receptor activates the DAF
      16/FOXO transcription factor, resulting in increased life span and resistance to
      some types of stress. We tested the hypothesis that inhibition of insulin
      signaling in Caenorhabditis elegans also increases hypertonic stress resistance.
      Genetic inhibition of DAF-2 or its downstream target, the AGE-1
      phosphatidylinositol 3-kinase, confers striking resistance to a normally lethal
      hypertonic shock in a DAF-16-dependent manner. However, insulin signaling is not
      inhibited by or required for adaptation to hypertonic conditions. Microarray
      studies have identified 263 genes that are transcriptionally upregulated by DAF
      16 activation. We identified 14 DAF-16-upregulated genes by RNA interference
      screening that are required for age-1 hypertonic stress resistance. These genes
      encode heat shock proteins, proteins of unknown function, and trehalose synthesis
      enzymes. Trehalose levels were elevated approximately twofold in age-1 mutants,
      but this increase was insufficient to prevent rapid hypertonic shrinkage.
      However, age-1 animals unable to synthesize trehalose survive poorly under
      hypertonic conditions. We conclude that increased expression of proteins that
      protect eukaryotic cells against environmental stress and/or repair stress
      induced molecular damage confers hypertonic stress resistance in C. elegans daf
      2/age-1 mutants. Elevated levels of solutes such as trehalose may also function
      in a cytoprotective manner. Our studies provide novel insights into stress
      resistance in animal cells and a foundation for new studies aimed at defining
      molecular mechanisms underlying these essential processes.

PMID- 15496476
TI  - Dynamic fibroblast cytoskeletal response to subcutaneous tissue stretch ex vivo
      and in vivo.
AB  - Cytoskeleton-dependent changes in cell shape are well-established factors
      regulating a wide range of cellular functions including signal transduction, gene
      expression, and matrix adhesion. Although the importance of mechanical forces on
      cell shape and function is well established in cultured cells, very little is
      known about these effects in whole tissues or in vivo. In this study we used ex
      vivo and in vivo models to investigate the effect of tissue stretch on mouse
      subcutaneous tissue fibroblast morphology. Tissue stretch ex vivo (average 25%
      tissue elongation from 10 min to 2 h) caused a significant time-dependent
      increase in fibroblast cell body perimeter and cross-sectional area (ANOVA, P <
      0.01). At 2 h, mean fibroblast cell body cross-sectional area was 201% greater in
      stretched than in unstretched tissue. Fibroblasts in stretched tissue had larger,
      "sheetlike" cell bodies with shorter processes. In contrast, fibroblasts in
      unstretched tissue had a "dendritic" morphology with smaller, more globular cell
      bodies and longer processes. Tissue stretch in vivo for 30 min had effects that
      paralleled those ex vivo. Stretch-induced cell body expansion ex vivo was
      inhibited by colchicine and cytochalasin D. The dynamic, cytoskeleton-dependent
      responses of fibroblasts to changes in tissue length demonstrated in this study
      have important implications for our understanding of normal movement and posture,
      as well as therapies using mechanical stimulation of connective tissue including
      physical therapy, massage, and acupuncture.

PMID- 15496477
TI  - Regulation of P2X7-induced pore formation and cell death in pericyte-containing
      retinal microvessels.
AB  - The purpose if this study was to elucidate how extracellular ATP causes cell
      death in the retinal microvasculature. Although ATP appears to serve as a
      vasoactive signal acting via P2X(7) and P2Y(4) purinoceptors, this nucleotide can
      kill microvascular cells of the retina. Because P2X(7) receptor activation causes
      transmembrane pores to form and microvascular cells to die, we initially surmised
      that pore formation accounted for ATP's lethality. To test this hypothesis, we
      isolated pericyte-containing microvessels from rat retinas, assessed cell
      viability using Trypan blue dye exclusion, detected pores by determining the
      uptake of the fluorescent dye YO-PRO-1, measured intracellular Ca(2+) with the
      use of fura-2, and monitored ionic currents via perforated patch pipettes. As
      predicted, ATP-induced cell death required P2X(7) receptor activation. However,
      we found that pore formation was minimal because ATP's activation of P2Y(4)
      receptors prevented P2X(7) pores from forming. Rather than opening lethal pores,
      ATP kills via a mechanism involving voltage-dependent Ca(2+) channels (VDCC). Our
      experiments suggest that when high concentrations of ATP caused nearly all
      microvascular P2X(7) receptor channels to open, the resulting profound
      depolarization opened VDCC. Consistent with lethal Ca(2+) influx via VDCC, ATP
      induced cell death was markedly diminished by the VDCC blocker nifedipine or a
      nitric oxide (NO) donor that inhibited microvascular VDCC. We propose that
      purinergic vasotoxicity is normally prevented in the retina by NO-mediated
      inhibition of VDCC and P2Y(4)-mediated inhibition of P2X(7) pore formation.
      Conversely, dysfunction of these protective mechanisms may be a previously
      unrecognized cause of cell death within the retinal microvasculature.

PMID- 15496478
TI  - Expression of constitutively stable hybrid hypoxia-inducible factor-1alpha
      protects cultured rat cardiomyocytes against simulated ischemia-reperfusion
      injury.
AB  - Preconditioning in cultured cardiomyocytes elevates the expression of several
      protective genes including Glut-4 and heat shock protein (HSP)70. Hypoxia
      inducible factor-1 (HIF-1) is known to mediate the transcriptional activation of
      hypoxia-responsive genes. In this study, we examined the effect of adenovirus
      mediated expression of constitutively stable hybrid forms of HIF-1alpha on
      cardiomyocyte viability and gene expression. Cultured neonatal rat cardiomyocytes
      were subjected to simulated ischemia-reperfusion with or without preinfection
      with recombinant adenoviral vectors [Ad2/HIF-1alpha/herpes simplex virus protein
      VP16 and Ad2/HIF-1alpha/nuclear factor-kappaB (NF-kappaB)]. Cellular viability
      and mRNA levels of several cardioprotective genes were measured. We demonstrated
      that infection with Ad2/HIF-1alpha/VP16 and Ad2/HIF-1alpha/NF-kappaB mimicked the
      upregulation of the mRNA levels of vascular endothelial growth factor (VEGF),
      Glut-1, Glut-4, HSP70, and inducible NO synthase (iNOS) and the protection of
      cultured neonatal rat cardiomyocytes by late-phase preconditioning against
      simulated ischemia-reperfusion. The same dose of a control viral vector
      expressing no transgene had no effect. Preconditioning also elevated HIF-1alpha
      protein levels. These results suggest that adenovirus-mediated expression of HIF
      1alpha/VP16 or HIF-1alpha/NF-kappaB, a constitutively stable hybrid
      transcriptional factor, protected cultured neonatal cardiomyocytes against
      simulated ischemia-reperfusion injury by inducing multiple protective genes.

PMID- 15496479
TI  - MEK1 restores migration of polyamine-depleted cells by retention and activation
      of Rac1 in the cytoplasm.
AB  - We previously showed that polyamines are required for proliferation and migration
      both in vivo and in a cultured intestinal epithelial cell (IEC-6) model. Wounding
      of the IEC-6 monolayer induced transient ERK activation, which was further
      enhanced by EGF. EGF stimulated migration in control and polyamine-depleted
      cells, but the degree of stimulation was significantly less in polyamine-depleted
      cells. Inhibition of MEK1 inhibited basal as well as EGF-induced ERK activation
      and migration. Expression of constitutively active (CA)-MEK and dominant-negative
      (DN)-MEK had significant effects on F-actin structure. CA-MEK increased stress
      fiber and lamellipodia formation, while DN-MEK showed loss of stress fibers and
      abnormal actin cytoskeletal structure. Unlike EGF, CA-MEK significantly increased
      migration of both control and polyamine-depleted cells. The most important and
      significant finding in this study was that polyamine depletion caused
      localization of Rac1 and RhoA to the nuclear as well as perinuclear regions.
      Interestingly, CA-MEK completely reversed the subcellular distribution of Rac1
      and RhoA proteins in polyamine-depleted cells. Polyamine depletion increased Rac1
      in the nuclear fraction and decreased it in the cytoplasmic and membrane
      fractions of vector-transfected cells. CA-MEK prevented accumulation of Rac1 in
      the nucleus. Polyamine depletion significantly decreased Rac1 activity during 6-h
      migration in vector-transfected cells. Cells transfected with CA-MEK had almost
      identical levels of activated Rac1 in all three groups. These results suggest
      that polyamine depletion prevents activation of Rac1 and RhoA by sequestering
      them to the nucleus and that expression of constitutively active MEK reverses
      this effect, creating the cellular localization required for activation.

PMID- 15496480
TI  - Mitochondrial regular arrangement in muscle cells: a "crystal-like" pattern.
AB  - The aim of this work was to characterize quantitatively the arrangement of
      mitochondria in heart and skeletal muscles. We studied confocal images of
      mitochondria in nonfixed cardiomyocytes and fibers from soleus and white
      gastrocnemius muscles of adult rats. The arrangement of intermyofibrillar
      mitochondria was analyzed by estimating the densities of distribution of
      mitochondrial centers relative to each other (probability density function). In
      cardiomyocytes (1,820 mitochondrial centers marked), neighboring mitochondria are
      aligned along a rectangle, with distance between the centers equal to 1.97 +/-
      0.43 and 1.43 +/- 0.43 microm in the longitudinal and transverse directions,
      respectively. In soleus (1,659 mitochondrial centers marked) and white
      gastrocnemius (621 pairs of mitochondria marked), mitochondria are mainly
      organized in pairs at the I-band level. Because of this organization, there are
      two distances characterizing mitochondrial distribution in the longitudinal
      direction in these muscles. The distance between mitochondrial centers in the
      longitudinal direction within the same I band is 0.91 +/- 0.11 and 0.61 +/- 0.07
      microm in soleus and white gastrocnemius, respectively. The distance between
      mitochondrial centers in different I bands is approximately 3.7 and approximately
      3.3 microm in soleus and gastrocnemius, respectively. In the transverse
      direction, the mitochondria are packed considerably closer to each other in
      soleus than in white gastrocnemius, with the distance equal to 0.75 +/- 0.22
      microm in soleus and 1.09 +/- 0.41 microm in gastrocnemius. Our results show that
      intermyofibrillar mitochondria are arranged in a highly ordered crystal-like
      pattern in a muscle-specific manner with relatively small deviation in the
      distances between neighboring mitochondria. This is consistent with the concept
      of the unitary nature of the organization of the muscle energy metabolism.

PMID- 15496481
TI  - Three-dimensional simulation of calcium waves and contraction in cardiomyocytes
      using the finite element method.
AB  - To investigate the characteristics and underlying mechanisms of Ca(2+) wave
      propagation, we developed a three-dimensional (3-D) simulator of cardiac
      myocytes, in which the sarcolemma, myofibril, and Z-line structure with Ca(2+)
      release sites were modeled as separate structures using the finite element
      method. Similarly to previous studies, we assumed that Ca(2+) diffusion from one
      release site to another and Ca(2+)-induced Ca(2+) release were the basic
      mechanisms, but use of the finite element method enabled us to simulate not only
      the wave propagation in 3-D space but also the active shortening of the myocytes.
      Therefore, in addition to the dependence of the Ca(2+) wave propagation velocity
      on the sarcoplasmic reticulum Ca(2+) content and affinity of troponin C for
      Ca(2+), we were able to evaluate the influence of active shortening on the
      propagation velocity. Furthermore, if the initial Ca(2+) release took place in
      the proximity of the nucleus, spiral Ca(2+) waves evolved and spread in a complex
      manner, suggesting that this phenomenon has the potential for arrhythmogenicity.
      The present 3-D simulator, with its ability to study the interaction between
      Ca(2+) waves and contraction, will serve as a useful tool for studying the
      mechanism of this complex phenomenon.

PMID- 15496482
TI  - Calmodulin interactions with IQ peptides from voltage-dependent calcium channels.
AB  - Calmodulin (CaM) functions as a Ca(2+) sensor for inactivation and, in some
      cases, facilitation of a variety of voltage-dependent Ca(2+) channels. A crucial
      determinant for CaM binding to these channels is the IQ motif in the COOH
      terminal tail of the channel-forming subunit. The binding of CaM to IQ peptides
      from Lc-, P/Q-, and R-type, but not N-type, voltage-dependent Ca(2+) channels
      increases the Ca(2+) affinity of both lobes of CaM, producing similar N- and C
      lobe Ca(2+) affinities. Ca(2+) associates with and dissociates from the N-lobe
      much more rapidly than the C-lobe when CaM is bound to the IQ peptides. Compared
      with the other IQ peptides, CaM-bound Lc-IQ has the highest Ca(2+) affinity and
      the most rapid rates of Ca(2+) association at both lobes, which is likely to make
      Ca(2+) binding to CaM, bound to this channel, less sensitive than other channels
      to intracellular Ca(2+) buffers. These kinetic differences in Ca(2+) binding to
      the lobes of CaM when bound to the different IQ motifs may explain both the
      ability of CaM to perform multiple functions in these channels and the
      differences in CaM regulation of the different voltage-dependent Ca(2+) channels.

PMID- 15496483
TI  - alpha1-Adrenoceptors stimulate a Galphas protein and reduce the transient outward
      K+ current via a cAMP/PKA-mediated pathway in the rat heart.
AB  - alpha(1)-Adrenoceptor stimulation prolongs the duration of the cardiac action
      potentials and leads to positive inotropic effects by inhibiting the transient
      outward K(+) current (I(to)). In the present study, we have examined the role of
      several protein kinases and the G protein involved in I(to) inhibition in
      response to alpha(1)-adrenoceptor stimulation in isolated adult rat ventricular
      myocytes. Our findings exclude the classic alpha(1)-adrenergic pathway:
      activation of the G protein G(alphaq), phospholipase C (PLC), and protein kinase
      C (PKC), because neither PLC, nor PKC, nor G(alphaq) blockade prevents the
      alpha(1)-induced I(to) reduction. To the contrary, the alpha(1)-adrenoceptor does
      not inhibit I(to) in the presence of protein kinase A (PKA), adenylyl cyclase, or
      G(alphas) inhibitors. In addition, PKA and adenylyl cyclase activation inhibit
      I(to) to the same extent as phenylephrine. Finally, we have shown a functional
      coupling between the alpha(1)-adrenoceptor and G(alphas) in a physiological
      system. Moreover, this coupling seems to be compartmentalized, because the
      alpha(1)-adrenoceptor increases cAMP levels only in intact cells, but not in
      isolated membranes, and the effect on I(to) disappears when the cytoskeleton is
      disrupted. We conclude that alpha(1)-adrenoceptor stimulation reduces the
      amplitude of the I(to) by activating a G(alphas) protein and the cAMP/PKA
      signaling cascade, which in turn leads to I(to) channel phosphorylation.

PMID- 15496484
TI  - Blue-yellow signals are enhanced by spatiotemporal luminance contrast in macaque
      V1.
AB  - We measured the color tuning of a population of S-cone-driven V1 neurons in
      awake, fixating monkeys. Analysis of randomly chosen color stimuli that were
      effective in evoking action potentials showed that these neurons received
      opposite sign input from the S cones and a combination of L and M cones.
      Surprisingly, these cells also responded to LM cone contrast irrespective of
      polarity, a nonlinear sensitivity that was masked by conventional linear analysis
      methods. Taken together, these observations can be summarized in a nonlinear
      model that combines nonopponent and opponent signals such that luminance contrast
      enhances color processing. These findings indicate that important aspects of the
      cortical representation of color cannot be described by classical linear
      analysis, and reveal a possible neural correlate of perceptual color-luminance
      interactions.

PMID- 15496485
TI  - Auditory-feedback control of temporal call patterns in echolocating horseshoe
      bats.
AB  - During flight, auditory feedback causes horseshoe bats to adjust the duration and
      repetition rate of their vocalizations in a context-dependent manner. As these
      bats approach a target, they make finely graded adjustments in call duration and
      interpulse interval (IPI), but their echolocation behavior is also characterized
      by abrupt transitions in overall temporal calling patterns. We investigated the
      relative contributions of two prominent acoustic cues, echo frequency and delay,
      toward the control of both graded and transitional changes in call duration and
      IPI. Echoes returning at frequencies above the emitted call frequency caused bats
      to switch from long single calls to pairs of short calls (doublets).
      Alternatively, increasing echo delay caused progressive increases in IPI but
      caused no accompanying changes in call duration. When frequency shifts were
      combined with changing echo delays, echo delay altered the IPIs occurring between
      doublets but not the IPI within a doublet. When the echo mimic was replaced by
      presentation of either an artificial constant-frequency (CF) stimulus or a
      frequency-modulated (FM) stimulus, each designed to mimic major components of the
      echo acoustic structure, we found that CF stimuli could trigger the switch to
      doublets, but changing CF delay had no influence on IPI, whereas the timing of an
      FM-sweep presentation had a strong effect on IPI. Because CF and FM sounds are
      known to be processed separately in the bat auditory system, the results indicate
      that at least two distinct neural feedback pathways may be used to control the
      temporal patterns of vocalization in echolocating horseshoe bats.

PMID- 15496486
TI  - Locomotor-like rhythms in a genetically distinct cluster of interneurons in the
      mammalian spinal cord.
AB  - Electrophysiological and morphological properties of genetically identified
      spinal interneurons were examined to elucidate their possible contribution to
      locomotor-like rhythmic activity in 1- to 4-day-old mice. In the transgenic mice
      used in our study, the HB9 promotor controlled the expression of the reporter
      gene enhanced green fluorescent protein (eGFP), giving rise to GFP+ motoneurons
      and ventral interneurons. However, only motoneurons and a small group of bipolar,
      GFP+ interneurons expressed the HB9 protein. The HB9(+)/GFP+ interneurons were
      clustered close to the medial surface in lamina VIII along segments L1-L3. The
      correlation between activity pattern in these visually identified interneurons
      and motoneuron output was examined using simultaneous whole cell and ventral root
      recordings. Neurochemically induced rhythmic membrane depolarizations in HB9/GFP
      interneurons were synchronous with ventral root rhythms, indicating that the
      interneurons received synaptic inputs from rhythm-generating networks. The
      frequency of excitatory postsynaptic currents significantly increased during
      ventral root bursts, but there was no change in the frequency of inhibitory
      postsynaptic currents during the cycle period. These data implied that HB9/GFP
      interneurons received primarily excitatory inputs from rhythmogenic interneurons.
      Neurobiotin-filled axon terminals were in close apposition to other neurons in
      the cluster and to motoneuron dendrites, raising the possibility that HB9/GFP
      interneurons formed synaptic connections with each other and with motoneurons.
      The expression of the vesicular glutamate transporter 2 in axon terminals of
      HB9/GFP interneurons indicated that these were glutamatergic interneurons. Our
      findings suggest that the visually identified HB9/GFP interneurons are premotor
      excitatory interneurons and putative constituents of networks generating
      locomotor rhythms in the mammalian spinal cord.

PMID- 15496487
TI  - Time-frequency representation of inspiratory motor output in anesthetized C57BL/6
      mice in vivo.
AB  - Inspiratory motor discharges, in addition to long-time-scale rhythmic oscillatory
      bursting, exhibit short-time-scale rhythmic oscillations that have been
      identified, and subsequently characterized, using power spectral analyses
      [predominantly fast-Fourier transforms (FFT)]. These analyses assume that the
      signal being analyzed is stationary; however, this is not the case for most
      biological signals, which exhibit varying degrees of nonstationarity. To overcome
      this limitation, time-frequency methods, which provide not only the frequency
      content but also information regarding the timing of these fast rhythmic
      oscillations (i.e., dynamics of spectral activity), should be used. Thus this
      study was performed to investigate the dynamic or time-varying features of
      spectral activity in inspiratory motor output. Both conventional time-invariant
      and time-frequency (time-varying) spectral analysis methods were performed on
      recordings of diaphragm EMG, phrenic nerve, and hypoglossal nerve discharges
      obtained from spontaneously breathing urethan-anesthetized adult C57BL/6 mice.
      Conventional time-invariant spectral analysis using a FFT algorithm revealed
      three dominant peaks in the power spectrum, which were located at 1) 20-46, 2) 83
      149, and 3) 177-227 Hz. Time-frequency spectral analysis using a generalized time
      frequency representation (TFR) with the smoothed pseudo-Wigner-Ville distribution
      (SPWD) kernel confirmed the general location of these spectral peaks, identified
      additional spectral peaks within the frequency ranges described above, and
      revealed a time-dependent expression of spectral activity within the inspiratory
      burst for each of the frequency ranges. Furthermore, this method revealed that 1)
      little or no spectral activity occurs during the initial portion of the
      inspiratory burst in any of the frequency ranges identified, 2) transient
      oscillations in the magnitude of spectral power exist where spectral activity
      occurs, and 3) total spectral power exhibits an augmenting pattern over the
      course of the inspiratory burst. These data, which provide the first description
      of spectral content in inspiratory motor discharges in adult mice, show that both
      time-invariant and time-varying spectral analysis methods are capable of
      identifying short-time-scale rhythmic oscillations in inspiratory motor discharge
      (as expected); however, the dynamic (i.e., timing) features of this oscillatory
      activity can only be obtained using the time-frequency method. We suggest that
      time-frequency methods, such as the SPWD, should be used in future studies
      examining short-time-scale (fast) rhythmic oscillations in inspiratory motor
      discharges, because additional insight into the neural control mechanisms that
      participate in inspiratory-phase neuronal and motoneuronal synchronization may be
      obtained.

PMID- 15496488
TI  - Decrease in synaptic transmission can reverse the propagation direction of
      epileptiform activity in hippocampus in vivo.
AB  - Most types of epileptiform activity with synaptic transmission have been shown to
      propagate from the CA3 to CA1 region in hippocampus. However, nonsynaptic
      epileptiform activity induced in vitro is known to propagate slowly from the
      caudal end of CA1 toward CA2/CA3. Understanding the propagation modes of
      epileptiform activity, and their causality is important to revealing the
      underlying mechanisms of epilepsy and developing new treatments. In this paper,
      the effect of the synaptic transmission suppression on the propagation of
      epilepsy in vivo was investigated by using multiple-channel recording probes in
      CA1. Nonsynaptic epileptiform activity was induced by calcium chelator EGTA with
      varied concentrations of potassium. For comparison, disinhibition synaptic
      epileptiform activity was induced by picrotoxin (PTX) with or without partial
      suppression of excitatory synaptic transmission. The propagation velocity was
      calculated by measuring the time delay between two electrodes separated by a
      known distance. The results show that in vivo nonsynaptic epileptiform activity
      propagates with a direction and velocity comparable to those observed in in vitro
      preparations. The direction of propagation for nonsynaptic activity is reversed
      from the PTX-induced synaptic activity. A reversal in propagation direction and
      change in velocity were also observed dynamically during the process of synaptic
      transmission suppression. Even a partial suppression of synaptic transmission was
      sufficient to significantly change the propagation direction and velocity of
      epileptiform activity. These results suggest the possibility that the measurement
      of propagation can provide important information about the synaptic mechanism
      underlying epileptic activity.

PMID- 15496489
TI  - Object perception in natural scenes: encoding by inferior temporal cortex
      simultaneously recorded neurons.
AB  - The firing of inferior temporal cortex neurons is tuned to objects and faces, and
      in a complex scene, their receptive fields are reduced to become similar to the
      size of an object being fixated. These two properties may underlie how objects in
      scenes are encoded. An alternative hypothesis suggests that visual perception
      requires the binding of features of the visual target through spike synchrony in
      a neuronal assembly. To examine possible contributions of firing synchrony of
      inferior temporal neurons, we made simultaneous recordings of the activity of
      several neurons while macaques performed a visual discrimination task. The
      stimuli were presented in either plain or complex backgrounds. The encoding of
      information of neurons was analyzed using a decoding algorithm. Ninety-four
      percent to 99% of the total information was available in the firing rate spike
      counts, and the contribution of spike timing calculated as stimulus-dependent
      synchronization (SDS) added only 1-6% of information to the total that was
      independent of the spike counts in the complex background. Similar results were
      obtained in the plain background. The quantitatively small contribution of spike
      timing to the overall information available in spike patterns suggests that
      information encoding about which stimulus was shown by inferior temporal neurons
      is achieved mainly by rate coding. Furthermore, it was shown that there was
      little redundancy (6%) between the information provided by the spike counts of
      the simultaneously recorded neurons, making spike counts an efficient population
      code with a high encoding capacity.

PMID- 15496490
TI  - Similar kinematic properties for ocular following and smooth pursuit eye
      movements.
AB  - Ocular following (OFR) is a short-latency visual stabilization response to the
      optic flow experienced during self-motion. It has been proposed that it
      represents the early component of optokinetic nystagmus (OKN) and that it is
      functionally linked to the vestibularly driven stabilization reflex during
      translation (translational vestibuloocular reflex, TVOR). Because no single eye
      movement can eliminate slip from the whole retina during translation, the OFR and
      the TVOR appear to be functionally related to maintaining visual acuity on the
      fovea. Other foveal-specific eye movements, like smooth pursuit and saccades,
      exhibit an eye-position-dependent torsional component, as dictated by what is
      known as the "half-angle rule" of Listing's law. In contrast, eye movements that
      stabilize images on the whole retina, such as the rotational vestibuloocular
      reflex (RVOR) and steady-state OKN do not. Consistent with the foveal
      stabilization hypothesis, it was recently shown that the TVOR is indeed
      characterized by an eye-position-dependent torsion, similar to pursuit eye
      movements. Here we have investigated whether the OFR exhibits three-dimensional
      kinematic properties consistent with a foveal response (i.e., similar to the TVOR
      and smooth pursuit eye movements) or with a whole-field stabilization function
      (similar to steady-state OKN). The OFR was elicited using 100-ms ramp motion of a
      full-field random dot pattern that moved horizontally at 20, 62, or 83 degrees/s.
      To study if an eye-position-dependent torsion is generated during the OFR, we
      varied the initial fixation position vertically within a range of +/-20 degrees .
      As a control, horizontal smooth pursuit eye movements were also elicited using
      step-ramp target motion (10, 20, or 30 degrees/s) at similar eccentric positions.
      We found that the OFR followed kinematic properties similar to those seen in
      pursuit and the TVOR with the eye-position-dependent torsional tilt of eye
      velocity having slopes that averaged 0.73 +/- 0.16 for OFR and 0.57 +/- 0.12
      (means +/- SD) for pursuit. These findings support the notion that the OFR, like
      the TVOR and pursuit, are foveal image stabilization systems.

PMID- 15496491
TI  - Spatiotemporal characteristics of neuronal sensory integration in the barrel
      cortex of the rat.
AB  - In primary sensory cortices, neuronal responses to a stimulus presented as part
      of a rapid sequence often differ from responses to an isolated stimulus. It has
      been reported that sequential stimulation of two whiskers produces facilitatory
      modulations of barrel cortex neuronal responses. These results are at odds with
      the well-known suppressive interaction that has been usually described. Herein,
      we have examined the dependency of response modulation on the spatiotemporal
      pattern of stimulation by varying the spatial arrangement of the deflected
      vibrissae, the temporal frequency of stimulation, and the time interval between
      whisker deflections. Extracellular recordings were made from primary
      somatosensory cortex of anesthetized rats. Two contralateral whiskers were
      stimulated at 0.5 and 8 Hz at intervals ranging from 0 to +/-30 ms. Response
      interactions were assessed during stimulation of the principal and adjacent
      whiskers, first from the same row and second from the same arc. When tested at
      0.5 Hz, 59% of single units showed a statistically significant suppressive
      interaction, whereas response facilitation was found in only 6% of cells. In
      contrast, at 8 Hz, a significant supralinear summation was observed in 19% of the
      cells, particularly for stimulations along an arc rather than along a row. Multi
      unit recordings showed similar results. These observations indicate that most of
      the interactions in the barrel cortex during two-whisker stimulation are
      suppressive. However, facilitation can be revealed when stimuli are applied at a
      physiological frequency and could be the basis for internal representations of
      the spatiotemporal pattern of the stimulus.

PMID- 15496492
TI  - Temporal evolution of oscillations and synchrony in GPi/muscle pairs in
      Parkinson's disease.
AB  - Both standard spectral analysis and time-dependent phase correlation techniques
      were applied to 27 pairs of tremor-related single units in the globus pallidus
      internus (GPi) and EMG of patients with Parkinson's disease (PD) undergoing
      stereotactic neurosurgery. Over long time-scales (approximately 60 s), GPi tremor
      related units were statistically coherent with restricted regions of the
      peripheral musculature displaying tremor. The distribution of pooled coherence
      across all pairs supports a classification of GPi cell/EMG oscillatory pairs into
      coherent or noncoherent. Analysis using approximately 2-s sliding windows shows
      that oscillatory activity in both GPi tremor units and muscles occurs
      intermittently over time. For brain/muscle pairs that are coherent, there is
      partial overlap in the times of oscillatory activity but, in most cases, no
      significant correlation between the times of oscillatory subepisodes in the two
      signals. Phase locking between coherent pairs occurs transiently; however, the
      phase delay is similar for different phase-locking subepisodes. Noncoherent pairs
      also show episodes of transient phase locking, but they occurred less frequently,
      and no preferred phase delay was seen across subepisodes. Tremor oscillations in
      pallidum and EMGs are punctuated by phase slips, which were classified as
      synchronizing or desynchronizing depending on their effect on phase locking. In
      coherent pairs, the incidence of synchronizing slips is higher than
      desynchronizing slips, whereas no significant difference was seen for noncoherent
      pairs. The results of this quantitative characterization of parkinsonian tremor
      provide a foundation for hypotheses about the structure and dynamical functioning
      of basal ganglia motor control networks involved in tremor generation.

PMID- 15496494
TI  - Correlation between gene expression and morphological alterations in baboon
      carotid after balloon dilatation injury.
AB  - Treatment for fibroproliferative restenosis after angioplasty and endovascular
      surgery is an unmet medical need. Rational therapy and drug design still lack the
      very basic knowledge about the underlying biological processes leading to
      pathological changes in the vessel wall. We have developed a primate model for
      vascular response to denudation-overstretch injury of baboon carotid artery. With
      this model, we have investigated the time course of vascular expression of 41,000
      human cDNA clones and correlated these changes with carotid histology and
      function. Analysis revealed 20,788 differentially regulated cDNA clones. After
      high stringency data selection, the most prominently regulated 1629 cDNA clones
      representing 1510 genes of known function were clustered. Genes corresponding to
      functional and anatomical alterations in the injured carotid wall were further
      aligned into functional groups according to Gene Ontology classification. The
      observed expression patterns faithfully reflected the functional and anatomical
      alterations observed in the vascular wall in response to injury. The analysis
      presents a tentative model for genomic response to balloon catheter injury and a
      road map to identify time-related genomic alterations in human vascular
      specimens.

PMID- 15496493
TI  - Syntaxin-1A binds to and modulates the Slo calcium-activated potassium channel
      via an interaction that excludes syntaxin binding to calcium channels.
AB  - From its position in presynaptic nerve terminals, the large conductance Ca(2+)
      activated K+ channel, Slo, regulates neurotransmitter release. Several other ion
      channels known to control neurotransmitter release have been implicated in
      physical interactions with the neurotransmitter release machinery. For example,
      the Ca(v)2.2 (N-type) Ca2+ channel binds to and is modulated by syntaxin-1A and
      SNAP-25. Furthermore, a close juxtaposition of Slo and Ca(v)2.2 is presumed to be
      necessary for functional coupling between the two channels, which has been shown
      in neurons. We report that Slo exhibits a strong association with syntaxin-1A.
      Robust co-immunoprecipitation of Slo and syntaxin-1A occurs from transfected
      HEK293 cells as well as from brain. However, despite this strong interaction and
      the known association between syntaxin-1A and the II-III loop of Ca(v)2.2, these
      three proteins do not co-immunoprecipitate in a trimeric complex from transfected
      HEK293 cells. The Slo-syntaxin-1A co-immunoprecipitation is not significantly
      influenced by [Ca2+]. Multiple relatively weak interactions may sum up to a tight
      physical coupling of full-length Slo with syntaxin-1A: the C-terminal tail and
      the S0-S1 loop of Slo each co-immunoprecipitate with syntaxin-1A. The presence of
      syntaxin-1A leads to reduced Slo channel activity due to an increased V(1/2) for
      activation in 100 nM, 1 muM, and 10 microM Ca2+, reduced voltage-sensitivity in 1
      microM Ca2+, and slower rates of activation in 10 microM Ca2+. Potential
      physiological consequences of the interaction between Slo and syntaxin-1A include
      enhanced excitability through modulation of Slo channel activity and reduced
      neurotransmitter release due to disruption of syntaxin-1A binding to the Ca(v)2.2
      II-III loop.

PMID- 15496495
TI  - Prevention and reversal of renal injury by leptin in a new mouse model of
      diabetic nephropathy.
AB  - Diabetic nephropathy is the leading cause of end-stage renal disease, for which
      effective therapy to prevent the progression at advanced stages remains to be
      established. There is also a long debate whether diabetic glomerular injury is
      reversible or not. Lipoatrophic diabetes, a syndrome caused by paucity of adipose
      tissue, is characterized by severe insulin resistance, dyslipidemia, and fatty
      liver. Here, we show that a genetic model of lipoatrophic diabetes (A-ZIP/F-1
      mice) manifests a typical renal injury observed in human diabetic nephropathy
      that is associated with glomerular hypertrophy, diffuse and pronounced mesangial
      widening, accumulation of extracellular matrix proteins, podocyte damage, and
      overt proteinuria. By crossing A-ZIP/F-1 mice with transgenic mice overexpressing
      an adipocyte-derived hormone leptin, we also reveal that leptin completely
      prevents the development of hyperglycemia and nephropathy in A-ZIP/F-1 mice.
      Furthermore, continuous leptin administration to A-ZIP/F-1 mice by minipump
      beginning at 40 weeks of age significantly alleviates the glomerular injury and
      proteinuria. These findings demonstrate the therapeutic usefulness of leptin at
      least for a certain type of diabetic nephropathy. The model presented here will
      serve as a novel tool to analyze the molecular mechanism underlying not only the
      progression but also the regression of diabetic nephropathy.

PMID- 15496496
TI  - Differential expression of mouse hepatic transporter genes in response to
      acetaminophen and carbon tetrachloride.
AB  - Drug-metabolizing enzymes and membrane transporters are responsible for the
      detoxication and elimination of xenobiotics from the body. The goal of this study
      was to identify alterations in mRNA expression of various transport and
      detoxication proteins in mouse liver after administration of the hepatotoxicants,
      acetaminophen or carbon tetrachloride. Therefore, male C57BL/6 J mice received
      acetaminophen (APAP, 200, 300, or 400 mg/kg, ip) or carbon tetrachloride (CCl4,
      10 or 25 microl/kg, ip). Plasma and liver samples were collected at 6, 24, and 48
      h for assessment of alanine aminotransferase (ALT) activity, total RNA isolation,
      and histopathological analysis of injury. Heme oxygenase-1 (Ho-1), NAD(P)H
      quinone oxidoreductase-1 (Nqo1), organic anion-transporting polypeptides
      (Oatp1a1, 1a4 and 1b2), sodium/taurocholate-cotransporting polypeptide (Ntcp),
      and multidrug resistance-associated protein (Mrp 1-6) mRNA levels in liver were
      determined using the branched DNA signal amplification assay. Hepatotoxic doses
      of APAP and CCl4 increased Ho-1 and Nqo1 mRNA levels by 22- and 2.5-fold,
      respectively, and reduced Oatp1a1, 1a4, and Ntcp mRNA levels in liver. By
      contrast, expression of Mrps 1-4 was increased after treatment with APAP and
      CCl4. Notably, a marked elevation of Mrp4 mRNA expression was observed 24 h after
      APAP 400 mg/kg (5-fold) and CCl4 25 microl/kg (37-fold). Collectively, these
      expression patterns suggest a coordinated regulation of both transport and
      detoxification genes during liver injury. This reduction in expression of uptake
      transporters, as well as enhanced transcription of detoxication enzymes and
      export transporters may limit the accumulation of potentially toxic products in
      hepatocytes.

PMID- 15496497
TI  - Signaling modulation of bile salt-induced necrosis in isolated rat hepatocytes.
AB  - Hydrophobic bile salts induce either necrosis or apoptosis depending on the
      severity of the injury caused by them. Since bile salt-induced apoptosis is
      influenced by Ca2+- and protein kinase-signaling pathways, and both necrosis and
      apoptosis share common initiating mechanisms, we analyzed whether these signaling
      cascades also influence bile salt-induced necrosis in isolated rat hepatocytes.
      Taurochenodeoxycholate (TCDC, 0.25-1.50 mM, 2 h) reduced, in a dose-dependent
      manner, the percentage of viable hepatocytes, and increased the release of the
      cytosolic enzyme, lactate dehydrogenase (LDH) and alanine aminotransferase
      (ALAT), and that of the plasma membrane enzyme, alkaline phosphatase (AP). The
      PKC inhibitors, H7 (100 microM) and chelerythrine (2.5 microM), both prevented
      significantly TCDC-induced necrosis. On the contrary, the PKA activator,
      dibutyryl-cAMP, exacerbated TCDC-induced cell damage in a dose-dependent manner;
      this effect was more likely due to cAMP-mediated PKA activation, as the PKA
      inhibitor, KT5720 (1 microM), counteracted this effect. Instead, the
      intracellular Ca2+ chelator, BAPTA/AM (20 microM), was without effect. TCDC (1
      mM) increased lipid peroxidation from 0.7 +/- 0.2 to 7.5 +/- 0.9 nmol of
      malondialdehyde per mg of protein, p < 0.001; the addition of the free radical
      scavenger, diphenyl-p-phenylendiamine, completely blocked this increase and
      prevented significantly TCDC-induced necrosis. PKC inhibition induced only a
      slight attenuation of TCDC-induced lipid peroxidation. Possible mechanisms
      accounting for the modulatory effect of signal transduction pathways on TCDC
      induced necrosis, including signaling influence on TCDC transport events and TCDC
      induced oxidative stress, are discussed.

PMID- 15496498
TI  - Peroxisome proliferator-activated receptors: mediators of phthalate ester-induced
      effects in the male reproductive tract?
AB  - Many phthalate ester plasticizers are classified as peroxisome proliferators
      (PP), a large group of industrial and pharmaceutical chemicals. Like PP, exposure
      to some phthalates increases hepatocyte peroxisome and cellular proliferation, as
      well as the incidence of hepatocellular adenomas in mice and rats. Most effects
      of PP are mediated by three nuclear receptors called peroxisome proliferator
      activated receptors (PPARalpha,beta,gamma). An obligate role for PPARalpha in PP
      induced events leading to liver cancer is well-established. Exposure of rats in
      utero or in the neonate to a subset of phthalate esters causes profound,
      sometimes irreversible malformations in the male reproductive tract. We review
      here the data that supports or discounts roles for PPARs in phthalate-induced
      testis toxicity including (1) toxic effects of phthalates on the male
      reproductive tract, (2) expression of PPARs in the testis, (3) activation of
      PPARs by phthalates, (4) role of PPARalpha in testis toxicity, (5) gene targets
      of phthalates involved in steroid biosynthesis and catabolism, and (6)
      interactions between PPARs and other nuclear receptors that play roles in testis
      development and homeostasis. Critical research needs are identified that will
      help determine the significance of PPARs in phthalate-induced effects in the rat
      male reproductive tract and the relevance of toxicity to humans.

PMID- 15496499
TI  - Effects of trichloroethylene and perchloroethylene on muscle contractile
      responses and epithelial prostaglandin release and acetylcholinesterase activity
      in swine trachea.
AB  - Trichloroethylene (TCE) and perchloroethylene (PERC) have been reported to induce
      respiratory complications such as airway hyperactivity and asthma. The present
      study was designed to investigate their influence on smooth muscle contraction
      and epithelial release of prostanoids in swine trachea. Results showed that TCE
      and PERC exposure did not alter the basal tone of tracheal smooth muscle.
      However, TCE and PERC concentration-dependently increased both ACh-induced and
      high K+-induced muscle contraction. In addition to potentiation of muscle
      contractile responses evoked by acetylcholine or histamine, pretreatment of
      smooth muscle with PERC at higher concentration significantly suppressed the
      relaxant activity of beta-adrenergic agonists. The epithelial prostaglandin
      (PG)E2, but not PGD2, release from tracheal epithelium was significantly
      increased by TCE and PERC. In addition, the acetylcholinesterse (AChE) activity
      of tracheal epithelia was reduced by TCE and PERC. In conclusion, our results
      suggest that the enhancement of spasmogen-evoked muscle contractile responses and
      epithelial PGE2 secretion, as well as reduction of epithelial AChE activity, may
      participate in airway impairment and hyperresponsiveness after TCE and PERC
      exposure.

PMID- 15496500
TI  - Preparation and application of biologically active fluorescent hyaluronan
      oligosaccharides.
AB  - We report the production of biologically active hyaluronan (HA) oligosaccharides
      labeled with the fluorophore 2-aminobenzoic acid (2AA). Oligosaccharides from 4
      to 40 residues in length were purified to homogeneity by ion exchange
      chromatography using a logarithmic gradient. Molecular weight and purity
      characterization of HA oligosaccharides is facilitated by 2AA derivatization
      because it enhances signals in MALDI-TOF MS and improves FACE (fluorophore
      assisted carbohydrate electrophoresis) analysis by avoiding the inverted
      parabolic migration characteristic of 2-aminoacridone (AMAC)-labeled sugars. The
      small size and shape of the fluorophore maintains the biological activity of the
      derivatized oligosaccharides, as demonstrated by their ability to compete for
      polymeric HA binding to the G1-domain of human recombinant versican (VG1). An
      electrophoretic mobility shift assay was used to study VG1 binding to labeled HA
      8-, 10-, 20-, 30-, and 40-mers, and although no stable VG1 binding was observed
      to labeled 8-mers, the equilibrium dissociation constant (100 nM) for VG1 with
      HA(10) was estimated from densitometry analysis of the free oligosaccharide.
      Interactions involving HA 20-, 30-, and 40-mers (proposed to be multivalent)
      could also be studied using this protocol. Oligosaccharides labeled with 2AA
      therefore show excellent potential as probes in fluorescence-based assays that
      investigate protein-carbohydrate interactions.

PMID- 15496501
TI  - Undersulfated, low-molecular-weight glycol-split heparin as an antiangiogenic
      VEGF antagonist.
AB  - Vascular endothelial growth factor (VEGF) represents a target for antiangiogenic
      therapies in a wide spectrum of diseases, including cancer. As a novel strategy
      to generate nonanticoagulant antiangiogenic substances exploiting binding to VEGF
      while preventing receptor engagement, we assessed the VEGF-antagonist activity of
      a low-molecular-weight (LMW) compound (ST2184, Mw = 5800) generated by
      depolymerization of an undersulfated glycol-split heparin derivative. The
      parental compound was obtained by introducing regular sulfation gaps along the
      prevalently N-sulfated heparin regions, followed by glycol-splitting of all
      nonsulfated uronic acid residues (approximately 50% of total uronic acid
      residues). ST2184 was endowed with a negligible anticoagulant activity after S.C.
      injection in mice. ST2184 binds VEGF165 as evaluated by its capacity to retard
      125I-VEGF165 electrophoretic migration in a gel mobility shift assay and to
      prevent VEGF165 interaction with heparin immobilized onto a BIAcore sensor chip.
      Unlike heparin, ST2184 was unable to present 125I-VEGF165 to its high-affinity
      receptors in endothelial cells and inhibited VEGF165-induced neovascularization
      in the chick embryo chorioallantoic membrane. Undersulfated, LMW glycol-split
      heparins may therefore provide the basis for the design of novel nonanticoagulant
      angiostatic compounds.

PMID- 15496502
TI  - Regulation of P2Y1 receptor-mediated signaling by the ectonucleoside triphosphate
      diphosphohydrolase isozymes NTPDase1 and NTPDase2.
AB  - Ectonucleoside triphosphate diphosphohydrolases (NTPDases) control the
      concentration of released extracellular nucleotides, but the precise
      physiological roles played by these isozymes in modulation of P2 receptor
      signaling remain unclear. Activation of the human P2Y(1) receptor was studied in
      the presence of NTPDase1 or NTPDase2 expressed either in the same cell as the
      receptor or in P2Y(1) receptor-expressing cells cocultured with NTPDaseexpressing
      cells. Coexpression of NTPDase1 with the P2Y(1) receptor resulted in increases in
      the EC(50) for 2'-methylthioadenosine 5'-diphosphate (2MeSADP; 12-fold), ADP (50
      fold), and ATP (10-fold) for activation of phospholipase C. Similar effects were
      observed when the P2Y(1) receptor and NTPDase1 were expressed on different cells.
      These results are explained by the capacity of NTPDase1 to hydrolyze both
      nucleoside triphosphates and diphosphates. NTPDase2 preferentially hydrolyzes
      nucleoside triphosphates, and the presence of NTPDase2 under either coexpression
      or coculture conditions did not change the EC(50) of 2MeSADP, ADP, or adenosine
      5'-O-(2-thiodiphosphate) for activation of the P2Y(1) receptor. However, the
      EC(50) for ATP was 15-fold lower in the presence of NTPDase2 than in cells
      expressing the P2Y(1) receptor alone. Whereas expression of NTPDase1 decreased
      basal activity of the P2Y(1) receptor, the presence of the NTPDase2 resulted in
      P2Y(1) receptor-dependent increases in basal activity. These results suggest that
      basal activity of the P2Y(1) receptor is maintained by paracrine or autocrine
      release of receptor agonists and that the biological and/or pharmacological
      response mediated by P2Y receptors in target tissues is highly dependent on the
      types of ectonucleotidases expressed in the vicinity of the receptor.

PMID- 15496503
TI  - Reciprocal regulation of agonist and inverse agonist signaling efficacy upon
      short-term treatment of the human delta-opioid receptor with an inverse agonist.
AB  - Rapid regulation of receptor signaling by agonist ligands is widely accepted,
      whereas short-term adaptation to inverse agonists has been little documented. In
      the present study, guanosine 5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS)
      binding and cAMP accumulation assays were used to assess the consequences of 30
      min exposure to the inverse agonist N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH
      (ICI174864) (1 microM) on delta-opioid receptor signaling efficacy. ICI174864
      pretreatment increased maximal effect (E(max)) for the partial agonist Tyr
      1,2,3,4-tetrahydroisoquinoline-Phe-Phe-OH (TIPP) at the two levels of the
      signaling cascade, whereas E(max) values for more efficacious agonists like (+)-4
      [(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N
      diethylbenzamide (SNC-80) and bremazocine were increased in [(35)S]GTPgammaS
      binding but not in cAMP accumulation assays. Pre-exposure to ICI174864 also
      induced a shift to the left in dose-response curves for bremazocine and TIPP. On
      the other hand, E(max) for the inverse agonist H-Tyr-TicPsi[CH(2)NH]Cha-Phe-OH
      was reduced in both assays, but no changes in potency were observed. For the
      weaker inverse agonist naloxone, E(max) in [(35)S]GTPgammaS binding was
      drastically modified because the drug turned from inverse agonist to agonist
      after ICI174864 pretreatment. Likewise, ICI174864 turned from inverse agonist to
      agonist when tested in cAMP accumulation assays. In both cases, inversion of
      efficacy was concomitant with marked increase in potency for agonist effects.
      Together with functional changes, short-term treatment with ICI174864 reduced
      basal receptor phosphorylation and increased immunoreactivity for Galpha(i3) in
      membrane preparations. Functional consequences of ICI174864 pretreatment were
      simulated in the cubic ternary complex model by increasing receptor/G protein
      coupling or G protein amount available for interaction with the receptor. Taken
      together, these data show that inverse agonists may induce rapid regulation in
      receptor signaling efficacy.

PMID- 15496504
TI  - Estrogen receptor activation of phosphoinositide-3 kinase, akt, and nitric oxide
      signaling in cerebral blood vessels: rapid and long-term effects.
AB  - Estrogen receptor regulation of nitric oxide production by vascular endothelium
      may involve rapid, membrane-initiated signaling pathways in addition to classic
      genomic mechanisms. In this study, we demonstrate using intact cerebral blood
      vessels that 17beta-estradiol rapidly activates endothelial nitric-oxide synthase
      (eNOS) via a phosphoinositide-3 (PI-3) kinase-dependent pathway. The effect is
      mediated by estrogen receptors (ERs), consistent with colocalization of ERalpha
      and caveolin-1 immunoreactivity at the plasma membrane of endothelial cells
      lining cerebral arteries. Treatment with 10 nM 17beta-estradiol for 30 min
      increased NO production, as measured by total nitrite assay, in cerebral vessels
      isolated from ovariectomized rats. This effect was significantly decreased by
      membrane cholesterol depletion with beta-methyl-cyclodextrin, the ER antagonist
      ICI 182,780 [fulvestrant (Faslodex)], and two inhibitors of PI-3 kinase:
      wortmannin and LY294002 [2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one
      hydrochloride]. In parallel with NO production, 17beta-estradiol treatment
      rapidly increased phosphorylation of both eNOS (p-eNOS) and Akt (p-Akt). PI-3
      kinase inhibitors also blocked the latter effects; together, these data are
      consistent with ER activation of the PI-3 kinase-p-Akt-p-eNOS pathway. ERalpha
      protein (66 and 50 kDa) coimmunoprecipitated with eNOS as well as with the
      p85alpha regulatory subunit of PI-3 kinase, further implicating ERalpha in kinase
      activation of eNOS. Little is known regarding the effects of estrogen on cellular
      kinase pathways in vivo; therefore, we compared cerebral blood vessels isolated
      from ovariectomized rats that were either untreated or given estrogen replacement
      for 4 weeks. Long-term estrogen exposure increased levels of cerebrovascular p
      Akt and p-eNOS as well as basal NO production. Thus, in addition to the rapid
      activation of PI-3 kinase, p-Akt, and p-eNOS, estrogen signaling via
      nontranscriptional, kinase mechanisms has long-term consequences for vascular
      function.

PMID- 15496505
TI  - Protein kinase C-independent effects of protein kinase D3 in glucose transport in
      L6 myotubes.
AB  - Protein kinase C (PKC) and protein kinase D (PKD) coordinate and regulate many
      fundamental cellular processes. In this study, we evaluate the role of classic
      and novel PKC (c/nPKC) and PKD in glucose transport in L6 myotubes. c/nPKC is
      either activated by short-term phorbol 12-myristate 13-acetate (PMA) treatment or
      down-regulated by prolonged PMA treatment at a high dose in L6 myotubes. Our
      results indicate that PMA treatments have little impact on basal and insulin
      stimulated glucose uptake and insulin-induced Akt activation. In contrast, the
      PKC inhibitors Go6976 [12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H
      indolo[2,3-a]pyrrolo[3,4-c] carbazole], Go6983 [2-[1-(3-dimethylaminopropyl)-5
      methoxyindol-3-yl]-3-(1H-indol-3-yl)maleimide], GF 109203X [bisindolylmaleimide
      I; 2-[1-(3-dimethylaminopropyl)indol-3-yl]-3-(1H-indol-3-yl)maleimide], and Ro 31
      8220 [bisindolylmaleimide IX; 2-{1-[3-(amidinothio)propyl]-1H-indol3-yl}-3-(1
      methylindol-3-yl)maleimide] block basal and insulin-stimulated glucose uptake,
      and their inhibitory effects persist upon down-regulation of c/nPKC by PMA,
      implying the presence of PKC-independent effectors in mediating their inhibition
      of glucose uptake. Go6976, the potent cPKC inhibitor that also effectively
      inhibits PKD, dose-dependently blocks basal glucose uptake in L6 myotubes,
      whereas Go6983, the nonselective PKC inhibitor that is ineffective for PKD, has
      little effect on basal glucose uptake, implying the involvement of PKD in this
      process. Most prominently, adenoviral gene expression of a dominant-negative PKD
      isoform, PKD3, primarily inhibits basal glucose uptake and, to a lesser extent,
      insulin-stimulated glucose uptake, whereas overexpression of wild-type PKD3
      significantly enhances basal glucose uptake. Moreover, expression of a PKD3
      targeted siRNA significantly inhibits basal glucose uptake. Taken together, our
      results indicate that PKD, specifically PKD3, directly contributes to insulin
      independent basal glucose uptake in L6 skeletal muscle cells.

PMID- 15496506
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin induces insulin-like growth factor binding
      protein-1 gene expression and counteracts the negative effect of insulin.
AB  - Recent epidemiological studies have revealed a possible correlation between
      exposure to high levels of dioxins or dioxin-like compounds and diabetes. Yet the
      interaction between insulin and dioxin actions remains elusive. We studied the
      regulation of insulin-like growth factor binding protein-1 (IGFBP-1), a protein
      involved in glucose homeostasis and whose expression is down-regulated by
      insulin. We showed that 2,3,7,8-tetrachorodibenzo-p-dioxin (TCDD) specifically
      induced IGFBP-1 mRNA in human hepatocytes and HepG2 human hepatoma cells (2.5-
      and 8-fold, respectively). Cellular and secreted IGFBP-1 protein levels were also
      up-regulated. Transfection and reporter assays showed that the IGFBP-1 promoter
      was activated by TCDD and that this activation was dependent on the integrity of
      a proximal xenobiotic-responsive element (XRE). This XRE, located near the
      insulin-glucocorticoid regulatory region, binds the aryl-hydrocarbon receptor. In
      agreement with previous studies, the IGFBP-1 promoter was down-regulated by
      insulin (50%); we show here that although TCDD activated the IGFBP-1 promoter 5-
      to 6-fold, the combination of TCDD and insulin led to an expression level of
      IGFBP-1 that was higher than basal level (2- to 3-fold activation). Similar
      regulations were observed for the endogenous IGFBP-1 mRNA. These data suggest
      that the xenobiotic-hormonal regulatory region of the IGFBP-1 promoter mediates
      an up-regulation of IGFBP-1 expression by TCDD even in the presence of insulin.
      Because IGFBP-1 modulates blood glucose levels, the up-regulation of IGFBP-1 by
      dioxins might account for the disruptive effects of these pollutants on glucose
      metabolism.

PMID- 15496507
TI  - Structural basis for epibatidine selectivity at desensitized nicotinic receptors.
AB  - The agonist binding sites of the fetal muscle nicotinic acetylcholine receptor
      are formed at the interfaces of alpha-subunits and neighboring gamma- and delta
      subunits. When the receptor is in the nonconducting desensitized state, the alpha
      gamma site binds the agonist epibatidine 200-fold more tightly than does the
      alpha-delta site. To determine the structural basis for this selectivity, we
      constructed gamma/delta-subunit chimeras, coexpressed them with complementary
      wild-type subunits in HEK 293 cells, and determined epibatidine affinity of the
      resulting complexes. The results reveal three determinants of epibatidine
      selectivity: gamma104-117/delta106-delta119, gamma164-171/delta166-177, and
      gammaPro190/deltaAla196. Point mutations reveal that three sequence differences
      within the gamma104-117/delta106-delta119 region are determinants of epibatidine
      selectivity: gammaLys104/deltaTyr106, gammaSer111/deltaTyr113, and
      gammaTyr117/deltaTyr119. In the delta-subunit, simultaneous mutation of these
      residues to their gamma equivalent produces high affinity, gamma-like epibatidine
      binding. However, converting gamma to delta affinity requires replacement of the
      gamma104-117 segment with delta sequence, suggesting interplay of residues in
      this region. The structural basis for epibatidine selectivity is explained by
      computational docking of epibatidine to a homology model of the alpha-gamma
      binding site.

PMID- 15496508
TI  - Palmitoylation and plasma membrane targeting of RGS7 are promoted by alpha o.
AB  - Regulator of G protein signaling (RGS) proteins modulate G protein signaling by
      acting as GTPase-activating proteins for G protein alpha-subunits. RGS7 belongs
      to a subfamily of RGS proteins that exist as dimers with the G protein beta(5)
      subunit. In this report, we addressed the mechanisms of plasma membrane
      localization of beta(5)RGS7. When expressed in human embryonic kidney 293 cells,
      beta(5)RGS7 was found to be cytoplasmic and soluble. Expression of alpha(o)
      promoted a strong redistribution of beta(5)RGS7 to the plasma membrane.
      Expression of alpha(q), however, failed to affect the subcellular localization of
      beta(5)RGS7. The constitutively active mutant alpha(o)R179C, like wild-type
      alpha(o), strongly recruited beta(5)RGS7 to plasma membranes; however, inactive
      alpha(o)G204A, RGS-insensitive alpha(o)G184S, and lipidation-deficient
      alpha(o)G2A were all defective in the ability to promote plasma membrane
      localization of beta(5)RGS7. In addition, palmitoylation of RGS7 was
      demonstrated, and palmitoylation required expression of alpha(o) or
      alpha(o)R179C. To examine potential palmitoylation sites of RGS7, several
      cysteines were substituted with serines. beta(5)RGS7C133S failed to localize to
      plasma membranes when coexpressed with alpha(o), suggesting cysteine 133 of RGS7
      as a putative palmitoylation site. Finally, deletion of amino acids 76 to 128 of
      RGS7, which includes part of the disheveled, EGL-10, pleckstrin (DEP) domain,
      prevented alpha(o)-mediated plasma membrane recruitment of beta(5)RGS7. These
      findings are the first to demonstrate Galpha-regulated plasma membrane
      localization and palmitoylation of beta(5)RGS7 and suggest that membrane
      targeting of beta(5)RGS7 is a complex process requiring at least RGS domain
      mediated interaction with alpha(o) and RGS7 palmitoylation.

PMID- 15496509
TI  - Agonists at mu-opioid receptors spin the wheels to keep the action going.
AB  - A study in this issue of Molecular Pharmacology on agonist-induced
      internalization of mu-opioid receptors during long-term opiate drug exposure is
      discussed. The study demonstrates the critical role of re-cycling of reactivated
      mu receptors back to the plasma membrane for the maintenance of agonist signaling
      during long-term opiate exposure.

PMID- 15496510
TI  - Role of mPKCI, a novel mu-opioid receptor interactive protein, in receptor
      desensitization, phosphorylation, and morphine-induced analgesia.
AB  - The human mu-opioid receptor (HmuOR) is a G-protein coupled receptor that
      mediates analgesia, euphoria and other important central and peripheral
      neurological functions. In this study, we found in a yeast two-hybrid screen that
      a protein kinase C-interacting protein (PKCI) specifically interacts with the C
      terminus of HmuOR. The interaction of PKCI with HmuOR was recapitulated in
      Chinese hamster ovary cells that express the full-length HmuOR and PKCI proteins.
      The affinity of HmuOR for an opioid ligand and its ability to mediate the
      activation of a G-protein were not altered by their interaction. However, the
      association of PKCI with HmuOR reduced agonist-induced inhibition of adenylyl
      cyclase and suppressed HmuOR desensitization partially at the G protein level and
      completely at the adenylyl cyclase level. Furthermore, PMA-induced, but not DAMGO
      induced, HmuOR phosphorylation was partially inhibited by the coexpression of
      PKCI, suggesting that PKCI exerts a selective regulatory effect on HmuOR
      signaling. This effect was specific to the mu-opioid receptor because delta
      opioid receptor desensitization was unaffected by PKCI. In addition, behavioral
      studies revealed that both basal and morphine-induced analgesia were
      significantly enhanced in the mutant mice that lacked expression of PKCI gene,
      and these mice developed a greater extent of tolerance to morphine analgesia.
      Taken together, these results suggest that PKCI functions as a negative regulator
      in HmuOR desensitization, phosphorylation, and in mediating morphine analgesia.

PMID- 15496511
TI  - His452Tyr polymorphism in the human 5-HT2A receptor destabilizes the signaling
      conformation.
AB  - Naturally occurring variation within the human 5-HT(2A) receptor results in an
      amino acid substitution in the carboxyl terminus of the receptor. This single
      nucleotide polymorphism (SNP), encoding a His452Tyr substitution, occurs at a
      frequency of 9% in the general population. It is noteworthy that this SNP has
      been linked to attention deficit hyperactivity disorder and has been associated
      with schizophrenic patients that do not respond to treatment with clozapine. To
      evaluate functional consequences of this SNP, agonist-stimulated signaling was
      investigated in NIH3T3 cells stably expressing either wild-type or 452Tyr variant
      receptors. The 452Tyr variant of the 5-HT(2a) receptor had reduced ability to
      activate phospholipases C and D, suggesting that signaling through both G(q) and
      G(13) pathways is hindered. This conclusion was supported by assays of G protein
      coupling, which documented a loss of agonist-induced high affinity binding and a
      decreased turnover of guanosine 5'-O-(3-[(35)S]thio)triphosphate after agonist
      stimulation. Kinetic analysis of time-course data revealed an altered
      desensitization phenotype, resulting in a blunted signal downstream of receptor
      activation. This diminished signaling implies that the His452Tyr variant receptor
      alters physiological responses, possibly contributing to psychiatric disease.

PMID- 15496512
TI  - RNF4 is a coactivator for nuclear factor Y on GTP cyclohydrolase I proximal
      promoter.
AB  - GTP cyclohydrolase I (GCH) is the rate-controlling enzyme in the production of
      tetrahydrobiopterin (BH4) that is essential for the synthesis of nitric oxide and
      catecholamines including dopamine and serotonin. Therefore, the regulation of GCH
      expression is important in determining the catecholamine levels in the brain
      under pathophysiological conditions. During the study of human disease dopa
      responsive dystonia, we found that coactivator RNF4 is involved in the GCH gene
      expression. Through serial deletion and mutagenesis studies of the GCH promoter,
      we defined the RNF4-responsive element on GCH proximal promoter as a CCAAT box.
      RNF4 did not possess specific DNA binding activity toward this CCAAT box, which
      suggests that RNF4 may be a coactivator of the CCAAT boxbinding protein nuclear
      factor Y (NF-Y). Cotransfection of a dominant-negative mutant of NF-Y resulted in
      a significant reduction in RNF4-mediated CCAAT box activation. In addition,
      overexpression of RNF4 could not activate the CCAAT box in Drosophila
      melanogaster SL2 cells, which are devoid of endogenous NF-Y, whereas
      overexpression of RNF4 and NF-Y could. Furthermore, immunoprecipitation
      experiments revealed the physical association between RNF4 and the NF-Y complex.
      These data indicate that RNF4 imposes functional importance on GCH promoter.

PMID- 15496513
TI  - Seasonal changes in mesotocin and localization of its receptor in the prostate of
      the brushtail possum (Trichosurus vulpecula).
AB  - The prostate gland in the brushtail possum grows and regresses seasonally. It has
      similarities to the human prostate and may therefore provide a unique model for
      investigating prostatic hyperplasia. Oxytocin has been implicated in the
      regulation of prostate growth in eutherian mammals, and the initial aim of this
      study was to identify and localize the marsupial equivalent, mesotocin, and its
      receptor in the prostate of the brushtail possum. Seasonal changes in prostatic
      mesotocin concentrations and receptor localization were then assessed and related
      to prostate growth. Mesotocin and mesotocin receptor gene transcripts with high
      sequence homology to eutherian oxytocin/oxytocin receptors were demonstrated, and
      mesotocin, neurophysin, and the receptor were all localized predominantly in the
      epithelial cells of the glandular acini. Western blot analysis confirmed the
      presence of a single immunoreactive receptor protein of approximately 60 Mr-3.
      Prostatic mesotocin concentrations were highest immediately before the increases
      in prostate weight associated with the autumn and spring breeding periods. At
      this time, mesotocin receptors were also present in the prostatic capsule in
      addition to those present in the glandular tissue. Mesotocin concentrations
      proceeded to decrease in association with the regression of prostate size toward
      the end of the breeding periods. No significant differences were present in serum
      testosterone or dihydrotestosterone throughout the year. The identification of
      mesotocin and its receptor in the possum prostate and the demonstration of
      seasonal changes in local mesotocin concentrations preceding changes in prostate
      size suggests that mesotocin may play a physiological role in regulating prostate
      growth and regression.

PMID- 15496514
TI  - A comprehensive survey of the genes involved in maturation and development of the
      rainbow trout ovary.
AB  - Development and maturation of the ovary requires precisely coordinated expression
      of specific gene classes to produce viable oocytes. We undertook identification
      of some of the genes involved in these processes by creating ovary-specific cDNA
      libraries by suppression subtractive hybridization and by microarray-based
      analyses. We present 5778 tissue- and sex-specific genes from subtracted ovary
      and testis libraries, many of which remain unidentified. A microarray containing
      3557 salmonid cDNAs was used to compare the transcriptomes of precocious ovary at
      three different stages during the second year of life with a reference (normal
      ovary) transcriptome. On average, approximately 240 genes were developmentally
      regulated during the study period from June to October. Classes of genes
      maintaining relatively steady-state levels of expression, such as those
      controlling tissue remodeling, immunoregulation, cell-cycle progression,
      apoptosis, and growth also were identified. Concurrent expression of various cell
      division and ubiquitin-mediated proteolysis regulators revealed the utility of
      microarray analysis to monitor important maturation events. We also report
      unequivocal evidence for expression of the transcripts that encode the common
      glycoprotein alpha, LH beta, FSH beta, thyroid-stimulating hormone beta, and
      retinol-binding protein in both the ovary and testis of trout.

PMID- 15496515
TI  - NF-kappaB is activated in the rat testis following exposure to mono-(2
      ethylhexyl) phthalate.
AB  - The process of spermatogenesis requires a delicate balance of proapoptotic and
      antiapoptotic signaling to maintain optimal sperm output. A major transcription
      factor known to regulate numerous apoptosis-related genes is NF-kappaB. Here we
      show that mono-(2-ethylhexyl) phthalate (MEHP, 1 g/kg) induces translocation of
      NF-kappaB subunits (p65, p50, and c-Rel) to germ cell nuclei in young rats
      (Postnatal Day 28) as early as 1 h after exposure. Immunohistochemistry of rat
      testes exposed to MEHP showed increased p50 and c-Rel presence in spermatocytes
      and spermatogonia. In addition, there was increased p65 nuclear positivity in
      Sertoli cells and germ cells after MEHP, while Rel-B localization was unchanged.
      These alterations correlated with increased nuclear NF-kappaB-binding activity
      after MEHP exposure, as shown by electrophoretic mobility shift assays of whole
      testis nuclear protein extracts. The increased activity of this transcription
      factor was associated with a transient protection of the seminiferous epithelium
      manifested as a decreased number of germ cell apoptotic nuclei measured by TUNEL
      assay 6 h after MEHP exposure. These results suggest that NF-kappaB is involved
      in the testicular response to MEHP-induced injury.

PMID- 15496516
TI  - Inhibition of the beta-catenin signaling pathway in blastocyst and uterus during
      the window of implantation in mice.
AB  - Beta-catenin, the mammalian homolog of Drosophila armadillo protein, was first
      identified as a cadherin-associated protein at cell-cell junctions. Another
      function of beta-catenin is the transduction of cytosolic signals to the nucleus
      in a variety of cellular contexts, which usually are elicited by the active form
      of beta-catenin. The aim of the present study was to examine the potential role
      of active beta-catenin in the mouse embryo and uterus during embryo implantation.
      Active beta-catenin was detected differentially in mouse embryos and uteri during
      the peri-implantation period. Aberrant activation of beta-catenin by LiCl, a well
      known glycogen synthase kinase-3 inhibitor, significantly inhibited blastocyst
      hatching and subsequent adhesion and outgrowth on fibronectin. Results obtained
      from pseudopregnant and implantation-delayed mice imply an important role for
      implanting blastocysts in the temporal and spatial changes of active beta-catenin
      in the uterus during the window of implantation. Collectively, these results
      suggest that the beta-catenin signaling pathway is inhibited in both blastocyst
      and uterus during the window of implantation, which may represent a new mechanism
      to synchronize the development of preimplantation embryos and differentiation of
      the uterus during this process.

PMID- 15496517
TI  - Profiling gene expression during the differentiation and development of the
      murine embryonic gonad.
AB  - The application of microarray technology to the study of mammalian organogenesis
      can provide greater insights into the steps necessary to elicit a functionally
      competent tissue. To this end, a temporal profile of gene expression was
      generated with the purpose of identifying changes in gene expression occurring
      within the developing male and female embryonic gonad. Gonad tissue was collected
      from mouse embryos at 11.5, 12.5, 14.5, 16.5, and 18.5 days postcoitum (dpc) and
      relative steady-state levels of mRNA were determined using the Affymetrix MGU74v2
      microarray platform. Statistical analysis produced 3693 transcripts exhibiting
      differential expression during male and/or female gonad development. At 11.5 dpc,
      the gonad is morphologically indifferent, but at 12.5 dpc, transitions to a male
      or female phenotype are discernible by the appearance of testicular cords. A
      number of genes are expressed during this period and many share similar
      expression profiles in both sexes. As expected, the expression of two well-known
      sex determination genes, specifically Sry and Sox9, is unique to the testis.
      Beyond 12.5 dpc, differential gene expression becomes increasingly evident as the
      male and female tissue morphologically and physiologically diverges. This is
      evident by two unique waves of transcriptional activity occurring after 14.5 dpc
      in the male and female. With this study, a large number of transcripts comprising
      the murine transcriptome can be examined throughout male and female embryonic
      gonad development and allow for a more complete description of gonad
      differentiation and development.

PMID- 15496518
TI  - RNAi: finding the elusive endonuclease.
AB  - RNA interference involves endonucleolytic cleavage of mRNAs at a site determined
      by complementary siRNAs. Initial cleavage leads to rapid degradation of the
      message, resulting in a corresponding reduction in the level of the encoded
      protein. Despite intensive study, the identity of the endonucleolytic activity
      (designated slicer) has remained obscure. Now, a combination of structural and
      biochemical analyses provide compelling evidence that human Argonaute2 (Ago2), a
      protein already known to be a key player in the RNAi pathway, is in fact the
      missing endonuclease.

PMID- 15496520
TI  - Novel application of sRNA: stimulation of ribosomal frameshifting.
AB  - Small RNAs play an important role in regulation of gene expression in eukaryotic
      and eubacterial cells by modulating gene expression both at the level of
      transcription and translation. Here, we show that short complementary RNAs can
      also affect gene expression by stimulating ribosomal frameshifting in vitro. This
      finding has important implications for understanding the process of ribosomal
      frameshifting and for the potential application of small RNAs in the treatment of
      diseases that are due to frameshift mutations.

PMID- 15496519
TI  - Under the Tucson sun: a meeting in the desert on mRNA decay.

PMID- 15496521
TI  - A base triple in the Tetrahymena group I core affects the reaction equilibrium
      via a threshold effect.
AB  - Previous work on group I introns has suggested that a central base triple might
      be more important for the first rather than the second step of self-splicing,
      leading to a model in which the base triple undergoes a conformational change
      during self-splicing. Here, we use the well-characterized L-21 ScaI ribozyme
      derived from the Tetrahymena group I intron to probe the effects of base-triple
      disruption on individual reaction steps. Consistent with previous results,
      reaction of a ternary complex mimicking the first chemical step in self-splicing
      is slowed by mutations in this base triple, whereas reaction of a ternary complex
      mimicking the second step of self-splicing is not. Paradoxically, mechanistic
      dissection of the base-triple disruption mutants indicates that active site
      binding is weakened uniformly for the 5'-splice site and the 5'-exon analog,
      mimics for the species bound in the first and second step of self-splicing.
      Nevertheless, the 5'-exon analog remains bound at the active site, whereas the 5'
      splice site analog does not. This differential effect arises despite the uniform
      destabilization, because the wild-type ribozyme binds the 5'-exon analog more
      strongly in the active site than in the 5'-splice site analog. Thus, binding into
      the active site constitutes an additional barrier to reaction of the 5'-splice
      site analog, but not the 5'-exon analog, resulting in a reduced reaction rate
      constant for the first step analog, but not the second step analog. This
      threshold model explains the self-splicing observations without the need to
      invoke a conformational change involving the base triple, and underscores the
      importance of quantitative dissection for the interpretation of effects from
      mutations.

PMID- 15496522
TI  - Two distinct Staufen isoforms in Xenopus are vegetally localized during
      oogenesis.
AB  - Localization of mRNA is an important way of generating early asymmetries in the
      developing embryo. In Drosophila, Staufen is intimately involved in the
      localization of maternally inherited mRNAs critical for cell fate determination
      in the embryo. We show that double-stranded RNA-binding Staufen proteins are
      present in the oocytes of a vertebrate, Xenopus, and are localized to the vegetal
      cytoplasm, a region where important mRNAs including VegT and Vg1 mRNA become
      localized. We identified two Staufen isoforms named XStau1 and XStau2, where
      XStau1 was found to be the principal Staufen protein in oocytes, eggs, and
      embryos, the levels of both proteins peaking during mid-oogenesis. In adults,
      Xenopus Staufens are principally expressed in ovary and testis. XStau1 was
      detectable throughout the oocyte cytoplasm by immunofluorescence and was
      concentrated in the vegetal cortical region from stage II onward. It showed
      partial codistribution with subcortical endoplasmic reticulum (ER), raising the
      possibility that Staufen may anchor mRNAs to specific ER-rich domains. We further
      showed that XStau proteins are transiently phosphorylated by the MAPK pathway
      during meiotic maturation, a period during which RNAs such as Vg1 RNA are
      released from their tight localization at the vegetal cortex. These findings
      provide evidence that Staufen proteins are involved in targeting and/or anchoring
      of maternal determinants to the vegetal cortex of the oocyte in Xenopus. The
      Xenopus oocyte should thus provide a valuable system to dissect the role of
      Staufen proteins in RNA localization and vertebrate development.

PMID- 15496523
TI  - The crystal structure of a high affinity RNA stem-loop complexed with the
      bacteriophage MS2 capsid: further challenges in the modeling of ligand-RNA
      interactions.
AB  - We have determined the structure to 2.8 A of an RNA aptamer (F5), containing 2'
      deoxy-2-aminopurine (2AP) at the -10 position, complexed with MS2 coat protein by
      soaking the RNA into precrystallised MS2 capsids. The -10 position of the RNA is
      an important determinant of binding affinity for coat protein. Adenine at this
      position in other RNA stem-loops makes three hydrogen bonds to protein functional
      groups. Substituting 2AP for the -10 adenine in the F5 aptamer yields an RNA with
      the highest yet reported affinity for coat protein. The refined X-ray structure
      shows that the 2AP base makes an additional hydrogen bond to the protein compared
      to adenine that is presumably the principal origin of the increased affinity.
      There are also slight changes in phosphate backbone positions compared to
      unmodified F5 that probably also contribute to affinity. Such phosphate movements
      are common in structures of RNAs bound to the MS2 T = 3 protein shell and
      highlight problems for de novo design of RNA binding ligands.

PMID- 15496524
TI  - Internal ribosome entry site drives cap-independent translation of reaper and
      heat shock protein 70 mRNAs in Drosophila embryos.
AB  - Translation is a sensitive regulatory step during cellular stress and the
      apoptosis response. Under such conditions, cap-dependent translation is reduced
      and internal ribosome entry site (IRES)-dependent translation plays a major role.
      However, many aspects of how mRNAs are translated under stress remain to be
      elucidated. Here we report that reaper mRNA, a pro-apoptotic gene from Drosophila
      melanogaster, is translated in a cap-independent manner. In Drosophila mutant
      embryos devoid of the eukaryotic initiation factor 4E (eIF4E), reaper
      transcription is induced and apoptosis proceeds. In vitro translation experiments
      using wild-type and eIF4E mutant embryonic extracts show that reporter mRNA
      bearing reaper 5' untranslated region (UTR) is effectively translated in a cap
      independent manner. The 5'UTR of reaper exhibits a high degree of similarity with
      that of Drosophila heat shock protein 70 mRNA, and both display IRES activity.
      Studies of mRNA association to polysomes in embryos indicate that both reaper and
      heat shock protein 70 mRNAs are recruited to polysomes under apoptosis or thermal
      stress. Our data suggest that heat shock protein 70 and reaper, two antagonizing
      factors in apoptosis, use a similar mechanism for protein synthesis.

PMID- 15496525
TI  - The PRC-barrel domain of the ribosome maturation protein RimM mediates binding to
      ribosomal protein S19 in the 30S ribosomal subunits.
AB  - The RimM protein in Escherichia coli is associated with free 30S ribosomal
      subunits but not with 70S ribosomes. A DeltarimM mutant is defective in 30S
      maturation and accumulates 17S rRNA. To study the interaction of RimM with the
      30S and its involvement in 30S maturation, RimM amino acid substitution mutants
      were constructed. A mutant RimM (RimM-YY-->AA), containing alanine substitutions
      for two adjacent tyrosines within the PRC beta-barrel domain, showed a reduced
      binding to 30S and an accumulation of 17S rRNA compared to wild-type RimM. The
      (RimM-YY-->AA) and DeltarimM mutants had significantly lower amounts of polysomes
      and also reduced levels of 30S relative to 50S compared to a wild-type strain. A
      mutation in rpsS, which encodes r-protein S19, suppressed the polysome- and 16S
      rRNA processing deficiencies of the RimM-YY-->AA but not that of the DeltarimM
      mutant. A mutation in rpsM, which encodes r-protein S13, suppressed the polysome
      deficiency of both rimM mutants. Suppressor mutations, found in either helices 31
      or 33b of 16S rRNA, improved growth of both the RimM-YY-->AA and DeltarimM
      mutants. However, they suppressed the 16S rRNA processing deficiency of the RimM
      YY-->AA mutant more efficiently than that of the DeltarimM mutant. Helices 31 and
      33b are known to interact with S13 and S19, respectively, and S13 is known to
      interact with S19. A GST-RimM but not a GST-RimM(YY-->AA) protein bound strongly
      to S19 in 30S. Thus, RimM likely facilitates maturation of the region of the head
      of 30S that contains S13 and S19 as well as helices 31 and 33b.

PMID- 15496527
TI  - Biopharmaceuticals derived from genetically modified plants.
AB  - Modern biotechnology has resulted in a resurgence of interest in the production
      of new therapeutic agents using botanical sources. With nearly 500 biotechnology
      products approved or in development globally, and with production capacity
      limited, the need for efficient means of therapeutic protein production is
      apparent. Through genetic engineering, plants can now be used to produce
      pharmacologically active proteins, including mammalian antibodies, blood product
      substitutes, vaccines, hormones, cytokines, and a variety of other therapeutic
      agents. Efficient biopharmaceutical production in plants involves the proper
      selection of host plant and gene expression system, including a decision as to
      whether a food crop or a non-food crop is more appropriate. Product safety issues
      relevant to patients, pharmaceutical workers, and the general public must be
      addressed, and proper regulation and regulatory oversight must be in place prior
      to commercial plant-based biopharmaceutical production. Plant production of
      pharmaceuticals holds great potential, and may become an important production
      system for a variety of new biopharmaceutical products.

PMID- 15496526
TI  - Probing microRNAs with microarrays: tissue specificity and functional inference.
AB  - MicroRNAs (miRNAs) are short, stable, noncoding RNAs involved in post
      transcriptional gene silencing via hybridization to mRNA. Few have been
      thoroughly characterized in any species. Here, we describe a method to detect
      miRNAs using micro-arrays, in which the miRNAs are directly hybridized to the
      array. We used this method to analyze miRNA expression across 17 mouse organs and
      tissues. More than half of the 78 miRNAs detected were expressed in specific
      adult tissues, suggesting that miRNAs have widespread regulatory roles in adults.
      By comparing miRNA levels to mRNA levels determined in a parallel microarray
      analysis of the same tissues, we found that the expression of target mRNAs
      predicted on the basis of sequence complementarity is unrelated to the tissues in
      which the corresponding miRNA is expressed.

PMID- 15496528
TI  - Life-threatening envenoming by the Saharan horned viper (Cerastes cerastes)
      causing micro-angiopathic haemolysis, coagulopathy and acute renal failure:
      clinical cases and review.
AB  - BACKGROUND: The desert horned vipers (Cerastes cerastes and C. gasperettii) are
      the most familiar snakes of the great deserts of North Africa and the Middle
      East, including the plains of Iraq. They are responsible for many human snake
      bites. In Western countries, they are popular among exotic-snake keepers. AIM: To
      investigate mechanisms of life-threatening envenoming and treatment. DESIGN:
      Clinical investigation. METHODS: Clinical and laboratory studies with measurement
      of serum venom antigen concentrations by enzyme immunoassay. RESULTS: Two men
      bitten while handling captive Saharan horned vipers (Cerastes cerastes) in Europe
      developed extensive local swelling and life-threatening systemic envenoming,
      characterized by coagulopathy, increased fibrinolysis, thrombocytopenia, micro
      angiopathic haemolytic anaemia and acute renal failure. The clinical picture is
      explicable by the presence in C. cerastes venom of several thrombin-like, Factor
      X-activating, platelet-aggregating, haemorrhagic and nephrotoxic components. In
      one case, prophylactic use of subcutaneous epinephrine may have contributed to
      intracranial haemorrhage. The roles in treatment of heparin (rejected) and
      specific antivenom (recommended) are discussed. DISCUSSION: Cerastes cerastes is
      capable of life-threatening envenoming in humans. Optimal treatment of envenoming
      is by early administration of specific antivenom, and avoidance of ineffective
      and potentially-dangerous ancillary methods.

PMID- 15496529
TI  - Mathematical estimation of the potential effect of vascular
      remodelling/dilatation on B-mode ultrasound intima-medial thickness.
AB  - BACKGROUND: Arterial diameter changes are known to impact wall thickness, but the
      clinical relevance of the changes is unclear. AIM: To use known mathematical
      relationships to estimate anticipated changes in arterial wall thicknesses
      occurring with enlargement of atherosclerotic regions. DESIGN: Mathematical
      relationships between a cylinder's diameter and its wall thickness were used to
      calculate the theoretical effect of diameter enlargement on the thickness of an
      atherosclerotic wall. METHODS: Equating the wall areas of two cylinders, one of
      smaller diameter than the other, allowed estimation of the degree of thickening
      that would be needed to maintain intima-medial thickness (IMT) after arterial
      remodelling. The difference in cylinder diameters was based on arterial diameter
      enlargement reported with atherosclerosis progression. Thus, the calculated wall
      changes estimate arterial changes which could go undetected if only IMT is
      measured by ultrasound. RESULTS: The expected IMT change for diameter enlargement
      is not a linear function of the diameter change, but varies depending upon
      initial size (diameter and IMT). Thus a 0.6 mm arterial diameter enlargement
      would be expected to cause a 0.039-0.235 mm change in IMT, depending on artery
      size. The estimated IMT change is similar to that associated with major
      atherosclerotic risk factors. DISCUSSION: The level of vascular remodelling
      reported with atherosclerosis could have a measurable impact on IMT, suggesting
      that indicators incorporating both diameter and IMT may be better disease
      indicators than IMT alone. Arterial diameters, as well as IMT, should be obtained
      in ultrasound studies of atherosclerosis.

PMID- 15496530
TI  - Asymptomatic isolated microscopic haematuria: long-term follow-up.
AB  - BACKGROUND: Evidence to support current diagnostic and management approaches to
      asymptomatic haematuria is lacking and based on short-term clinical observation.
      AIM: To ascertain the natural history and long-term outcome of asymptomatic and
      isolated haematuria, and to determine the clinical correlates of adverse renal
      events. DESIGN: Prospective observational referral-based study. METHODS: We
      evaluated 90 consecutive patients with isolated microscopic haematuria, first
      seen between 1985 and 1996 at an out-patient nephrology clinic. We defined
      adverse renal events as the development of proteinuria (> 0.5 g/24 h) on two
      consecutive occasions, development of hypertension, or impaired renal function
      characterized by glomerular filtration rate (GFR) of <60 ml/min/1.73 m(2) for 3
      months or more. RESULTS: There were 24 males and 66 females, median follow-up 5.2
      years (total 442 patient-years). Mean age at presentation was 39 +/- 13 years.
      Fifteen (17%) had complete resolution of microscopic haematuria. One (1%) had
      transitional cell carcinoma of urinary bladder 20 months after initial
      presentation. Twelve (13%) developed hypertension, and 10 (11%) proteinuria. Only
      one developed chronic renal failure, 2.3 years after initial presentation.
      Altogether, 16 (19%) developed at least one adverse event, after a mean 42
      months. Neither history of renal biopsy nor histological diagnosis of glomerular
      disease was predictive of renal events. Three independent variables were
      predictive of adverse renal events: baseline proteinuria (RR per 0.1 g/day 2.04;
      95%CI 1.13-3.68; p = 0.018); MDRD-estimated GFR at presentation (RR per 10
      ml/min/1.73 m(2) decrement 2.01; 95%CI 1.09-3.71; p = 0.025); and baseline serum
      urate (RR per 100 micromol/l 1.02; 95%CI 1.01-1.03; p = 0.009). DISCUSSION:
      Asymptomatic microscopic haematuria can lead to adverse renal events, and
      warrants nephrologist evaluation and regular follow-up. Its isolated microscopic
      haematuria is closely related to early hints of chronic kidney disease, such as
      low-grade proteinuria and renal insufficiency, as well as hyperuricaemia.

PMID- 15496531
TI  - Unexplained swelling symptoms in women (idiopathic oedema) comprise one component
      of a common polysymptomatic syndrome.
AB  - BACKGROUND: Non-menstrually-related swelling symptoms (idiopathic oedema) are
      common in women. The community prevalence of such symptoms, their association
      with other symptoms, and their underlying aetiology, are uncertain. AIM: To
      determine the community prevalence of swelling symptoms and the independent
      contributions of major risk factors. DESIGN: Comparison of major risk factors in
      women with and without swelling symptoms. METHODS: We assessed 196 women
      attending a menopause clinic, 201 women attending a fracture clinic and 201 women
      attending their general practitioner. Each documented family histories of
      swelling symptoms and diabetes mellitus, age, height and current weight. Women
      attending the menopause and fracture clinics also completed Visual Analogue
      Symptom (VAS) scales documenting the perceived severity of swelling symptoms, and
      of 20 affective, somatic and functional autonomic symptoms. The independent
      contributions of risk factors to swelling symptom risk were estimated by logistic
      regression analysis. RESULTS: Of those attending a fracture clinic or their
      general practitioner, 28% and 33%, respectively, experienced non-menstrually
      related swelling symptoms in the month before interview. Severe (RR 43, 95%CI 16
      112, p < 0.001) and moderate (RR 7.8, 95%CI 4-15, p < 0.001) affective symptoms,
      a family history of swelling symptoms (RR 4.5, 95%CI 2.3-8.8, p < 0.001) and a
      body mass index (BMI) >or=25 kg/m(2) (RR 4.8, 95%CI 2.5-8.9, p < 0.001) were
      significantly associated with the presence of mild to severe swelling symptoms
      (VAS 1-9). The prevalence of swelling symptoms increased from 8% in women with no
      risk factors to 100% in women with three risk factors, which included severe
      affective symptoms. DISCUSSION: Affective symptom severity provides the principal
      independent contribution to swelling symptom risk. BMI >or=25 and a family
      history of swelling symptoms provide smaller independent contributions. The
      nature of the mechanisms underlying these associations remains uncertain.

PMID- 15496532
TI  - Using subcutaneous fluids to rehydrate older people: current practices and future
      challenges.

PMID- 15496533
TI  - Bones, muscle, medals and privacy.

PMID- 15496534
TI  - Unspeakable.

PMID- 15496535
TI  - CYP3A4 polymorphisms--potential risk factors for breast and prostate cancer: a
      HuGE review.
AB  - The steroid hydroxylase CYP3A4 is the most abundant P-450 enzyme in the human
      liver, and CYP3A enzymes metabolize more than 50% of prescription drugs. The
      CYP3A4 gene is expressed in the liver, gut, colon, prostate, and breast.
      Individual variation in CYP3A4 may play a role in breast and prostate
      carcinogenesis through modulation of sex hormone metabolite levels.
      Alternatively, CYP3A4 can metabolically activate exogenous carcinogens. CYP3A4
      activity varies widely in humans, and more than 78 DNA sequence polymorphisms are
      known. These observations prompted the hypothesis that variant CYP3A4 may be
      involved in breast and prostate cancer. Two epidemiologic studies of breast
      cancer and five of prostate cancer examined CYP3A4 genotypes. A US study showed
      that inheritance of CYP3A4*1B correlates with early menarche, a breast cancer
      risk factor. However, an Australian breast cancer case-control study found no
      association with CYP3A4*1B. Two Scottish prospective studies showed CYP3A4*1B to
      be a risk factor for prostate cancer among men with benign prostatic hyperplasia.
      Three other studies were undertaken in the United States: two were case-only
      studies and the other was a case-sibling control study. Although results for
      African Americans were inconsistent, these studies suggested that CYP3A4*1B was
      associated with markers of advanced disease. These observations support the
      notion that development of robust, conventional molecular epidemiologic case
      control studies to address these questions, including gene-gene and gene
      environment interactions, will be timely.

PMID- 15496536
TI  - CYP1A1, cigarette smoking, and colon and rectal cancer.
AB  - Cytochrome P-450 (CYP) is involved in the activation and metabolism of polycyclic
      aromatic hydrocarbons in tobacco products. The authors evaluated the association
      of two polymorphisms in the CYP1A1 gene--the noncoding Msp I polymorphism in the
      3'-untranslated region and the Ile462Val polymorphism in exon 7--with colon and
      rectal cancer. The authors used data from two incident case-control studies of
      colon cancer (1,026 cases and 1,185 controls) and rectal cancer (820 cases and
      1,036 controls) conducted in California and Utah (1991-2002). CYP1A1 genotype was
      not associated with colon or rectal cancer. Having GSTM1 present, a CYP1A1
      variant allele, and the rapid-acetylator NAT2 imputed phenotype was associated
      with increased risk of colon cancer (odds ratio = 1.7, 95% confidence interval:
      1.2, 2.3). Among men, the greatest colon cancer risk was observed for having any
      CYP1A1 variant allele and currently smoking (odds ratio = 2.5, 95% confidence
      interval: 1.3, 4.8; Wald chi(2)test: p < 0.01). Assessment of GSTM1 and CYP1A1
      and rectal cancer in men showed a twofold elevation in risk for more than 20 pack
      years of smoking, except among those with GSTM1 present who had a variant CYP1A1
      allele. These data support the association between smoking and colon and rectal
      cancer. Smoking may have a greater impact on colorectal cancer risk based on
      CYP1A1 genotype; this might further be modified by GSTM1 for rectal cancer risk.

PMID- 15496537
TI  - Arsenic concentrations in prediagnostic toenails and the risk of bladder cancer
      in a cohort study of male smokers.
AB  - At high concentrations, inorganic arsenic can cause bladder cancer in humans.
      However, it is unclear whether low exposure to inorganic arsenic in drinking
      water (<100 microg/liter) is related to bladder cancer risk. No study has been
      known to use biomarkers to assess the relation between individual arsenic
      exposure and bladder cancer risk. Toenail samples provide an integrated measure
      of internal arsenic exposure and reflect long-term exposure. The authors examined
      the relation between toenail arsenic levels and bladder cancer risk among
      participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a
      cohort of Finnish male smokers aged 50-69 years. Data for 280 incident bladder
      cancer cases, identified between baseline (1985-1988) and April 1999, were
      available for analysis. One control was matched to each case on the basis of age,
      toenail collection date, intervention group, and smoking duration. Arsenic levels
      in toenail samples were determined by using neutron activation analysis. Logistic
      regression analyses were performed to estimate odds ratios. Arsenic toenail
      concentrations in this Finnish study were similar to those reported in US studies
      (range: 0.02-17.5 microg/g). The authors observed no association between
      inorganic arsenic concentration and bladder cancer risk (odds ratio = 1.13, 95%
      confidence interval: 0.70, 1.81 for the highest vs. lowest quartile). These
      findings suggest that low-level arsenic exposure is unlikely to explain a
      substantial excess risk of bladder cancer.

PMID- 15496538
TI  - Commuting physical activity and risk of colon cancer in Shanghai, China.
AB  - Colon cancer incidence rates have been rapidly increasing in Shanghai, China, for
      reasons still unclear. Low physical activity is a known risk factor for colon
      cancer. The authors examined the effects of physical activity, particularly
      commuting physical activity, and its joint effects with body mass index on colon
      cancer risk in a population-based, case-control study. The study included 931
      incident colon cancer patients and 1,552 randomly selected controls in Shanghai
      between 1990 and 1993. Colon cancer risk was significantly reduced among subjects
      with high commuting physical activity (odds ratio (OR) = 0.52, 95% confidence
      interval (CI): 0.27, 0.87 for men; OR = 0.56, 95% CI: 0.21, 0.91 for women),
      particularly among those who had high commuting physical activity for at least 35
      years (OR = 0.34, 95% CI: 0.09, 0.76 for men; OR = 0.31, 95% CI: 0.07, 0.72 for
      women). Commuting physical activity significantly modified the risk conferred by
      high body mass index, with the highest risk observed among those at the highest
      quintile of body mass index and the lowest activity level (OR = 6.43, 95% CI:
      1.82, 8.54 for men; OR = 7.42, 95% CI: 2.84, 10.01 for women). Our results
      suggest that regular and frequent physical activity over a long period of time
      protects from colon cancer and significantly modifies the body mass index
      associated risk.

PMID- 15496539
TI  - Risk factors for breast cancer in elderly women.
AB  - As the population ages, an increasing fraction of women diagnosed with breast
      cancer will be elderly. Heterogeneity of breast cancer risk factors between pre-
      and postmenopausal women is recognized, but few studies have examined elderly
      women specifically. The authors describe the age-specific influence of risk
      factors for postmenopausal breast cancer, with emphasis on women aged 75 or more
      years. Among 36,658 members of the Iowa Women's Health Study (1986-2001), a
      population-based cohort study, 428 incident breast cancers were diagnosed in
      women aged 55-64 years, 1,297 in women aged 65-74 years, and 561 in women aged 75
      84 years. Women with a body mass index (weight (kg)/height (m)(2)) in the highest
      versus the lowest quartile were at increased risk of breast cancer at age 75 or
      more years (adjusted hazard ratio = 1.44, 95% confidence interval (CI): 1.12,
      1.84). Family history of breast cancer (hazard ratio = 1.54, 95% CI: 1.24, 1.93
      for a first-degree family history vs. none) and an older age at menopause
      (p(trend) = 0.07) conferred increased risk for women aged 75 or more years, and a
      high number of livebirths was protective (hazard ratio = 0.67, 95% CI: 0.51, 0.88
      for five or more births compared with one or two). Obesity, a modifiable risk
      factor, remained positively associated with breast cancer for all age groups of
      postmenopausal women.

PMID- 15496540
TI  - Pesticides and lung cancer risk in the agricultural health study cohort.
AB  - The authors examined the relation between 50 widely used agricultural pesticides
      and lung cancer incidence in the Agricultural Health Study, a prospective cohort
      study of 57,284 pesticide applicators and 32,333 spouses of farmer applicators
      with no prior history of lung cancer. Self-administered questionnaires were
      completed at enrollment (1993-1997). Cancer incidence was determined through
      population-based cancer registries from enrollment through December 31, 2001. A
      lung cancer standardized incidence ratio of 0.44 (95% confidence interval: 0.39,
      0.49) was observed overall, due in large part to a low cigarette smoking
      prevalence. Two widely used herbicides, metolachlor and pendimethalin (for low
      exposed groups to four higher exposure categories: odds ratio (OR) = 1.0, 1.6,
      1.2, 5.0; p(trend) = 0.0002; and OR = 1.0, 1.6, 2.1, 4.4; p(trend) = 0.003,
      respectively), and two widely used insecticides, chlorpyrifos and diazinon (OR =
      1.0, 1.1, 1.7, 1.9; p(trend) = 0.03; and OR = 1.0, 1.6, 2.7, 3.7; p(trend) =
      0.04, respectively), showed some evidence of exposure response for lung cancer.
      These excesses could not be explained by previously identified lung cancer risk
      factors. The usage levels in this cohort are considerably higher than those
      typically experienced by the general population. An excess risk among spouses
      directly exposed to pesticides could not be evaluated at this time.

PMID- 15496541
TI  - Multivitamin use and the risk of preterm birth.
AB  - Previous research suggests that multivitamin use before and during pregnancy can
      diminish diet-related deficiencies of certain micronutrients and potentially
      prevent preterm birth. To assess this association, the authors performed an
      analysis by using data from the Pregnancy, Infection, and Nutrition Study (n =
      2,010). Women were recruited at 24-29 weeks of pregnancy from four prenatal care
      clinics in North Carolina from August 1995 to June 2000. For women who took
      multivitamins prior to pregnancy, compared with nonusers, the adjusted risk ratio
      was 0.50 (95% confidence interval: 0.20, 1.25) for delivering preterm (<37
      weeks). In contrast, prenatal and periconceptional use, compared with nonuse,
      were not related to preterm birth, with adjusted risk ratios of 1.1.
      Preconceptional multivitamin use was inversely associated with both early (<35
      weeks; adjusted odds ratio = 0.59, 95% confidence interval: 0.12, 2.76) and late
      (35-36 weeks; adjusted odds ratio = 0.40, 95% confidence interval: 0.12, 1.40)
      preterm birth; findings were based on only two and three exposed cases,
      respectively. These results suggest that, compared with nonusers, women who take
      multivitamin supplements prior to conception may have a reduced risk of preterm
      birth, but further studies are needed with a larger sample of preconceptional
      users.

PMID- 15496542
TI  - Racial difference in lung function in African-American and White children: effect
      of anthropometric, socioeconomic, nutritional, and environmental factors.
AB  - African-American children have lower lung volumes than White children. However,
      the contributions of anthropometric, socioeconomic, nutritional, and
      environmental factors to this difference are unknown. From participants in the
      Third National Health and Nutrition Examination Survey (1988-1994), the authors
      selected 1,462 healthy nonsmoking children (623 White and 839 African-American)
      aged 8-17 years. The African-American children were taller and heavier but had
      lower lung function. African Americans were poorer and had lower levels of the
      antioxidant vitamins A and C and alpha-carotene. The authors performed regression
      analyses using data on anthropometric, socioeconomic, and nutritional factors and
      smoke exposure. Adjustment for sitting height explained 42-53% of the racial
      difference. Socioeconomic factors and antioxidant vitamin levels accounted for an
      additional 7-10%. Overall, the authors could account for only 50-63% of the
      racial difference. Exposure to tobacco in the home was weakly associated with
      forced expiratory volume in 1 second in girls, accounting for 1% of the
      difference. In children aged 8-12 years (n = 752), birth weight explained 3-5% of
      the racial difference, whereas in-utero exposure to maternal smoking had no
      significant effect. The authors conclude that in healthy children, the major
      explanatory variable for the racial difference in lung function is body habitus;
      socioeconomic, nutritional, and environmental confounders play a smaller role.

PMID- 15496543
TI  - Bone density-related predictors of blood lead level among peri- and
      postmenopausal women in the United States: The Third National Health and
      Nutrition Examination Survey, 1988-1994.
AB  - Because of the long half-life of lead stored in bone (years), skeletal lead
      stores may be a source of endogenous lead exposure during periods of increased
      bone demineralization, such as menopause. To test the hypothesis that
      postmenopausal bone resorption increases blood lead levels, the authors examined
      cross-sectional associations of bone density-related factors with blood lead
      levels among women aged 40-59 years from the Third National Health and Nutrition
      Examination Survey (1988-1994). Factors related to bone turnover were significant
      predictors of blood lead level. Bone mineral density was significantly inversely
      related to blood lead levels in log-linear multivariate models that adjusted for
      age, race/ethnicity, smoking, education, household income, alcohol use, and
      residence (urban/rural). With menopausal status added to the model, naturally and
      surgically menopausal women had adjusted median blood lead levels that were 25%
      and 30% higher, respectively, than those of premenopausal women (2.0 microg/dl).
      Current use of hormone replacement therapy was associated with significantly
      lower adjusted median blood lead levels (1.8 microg/dl) than past use (2.6
      microg/dl) and never use (2.2 microg/dl). Lead stored in bone may significantly
      increase blood lead levels in perimenopausal women because of postmenopausal bone
      mineral resorption. Attention to factors that prevent bone loss may lessen or
      prevent this endogenous lead exposure.

PMID- 15496544
TI  - Physical activity and changes in weight and waist circumference in midlife women:
      findings from the Study of Women's Health Across the Nation.
AB  - Controversy exists regarding the extent to which age, menopausal status, and/or
      lifestyle behaviors account for the increased weight, fat mass, and central
      adiposity experienced by midlife women. To address this question, the authors
      longitudinally examined the relations of aging, menopausal status, and physical
      activity to weight and waist circumference in 3,064 racially/ethnically diverse
      women aged 42-52 years at baseline who were participating in the Study of Women's
      Health Across the Nation (SWAN), an observational study of the menopausal
      transition. Over 3 years of follow-up (1996-1997 to 1999-2000), mean weight
      increased by 2.1 kg (standard deviation (SD), 4.8) or 3.0% (SD, 6.5) and mean
      waist circumference increased by 2.2 cm (SD, 5.4) or 2.8% (SD, 6.3). Change in
      menopausal status was not associated with weight gain or significantly associated
      with increases in waist circumference. A one-unit increase in reported level of
      sports/exercise (on a scale of 1-5) was longitudinally related to decreases of
      0.32 kg in weight (p < 0.0001) and 0.10 cm in waist circumference (not
      significant). Similar inverse relations were observed for daily routine physical
      activity (biking and walking for transportation and less television viewing).
      These findings suggest that, although midlife women tend to experience increases
      in weight and waist circumference over time, maintaining or increasing
      participation in regular physical activity contributes to prevention or
      attenuation of those gains.

PMID- 15496545
TI  - Re: "cellular telephone use and risk of acoustic neuroma".

PMID- 15496546
TI  - Re: "cellular telephone use and risk of acoustic neuroma".

PMID- 15496548
TI  - Re: "Do men have a higher case fatality rate of severe acute respiratory syndrome
      than women do?".

PMID- 15496549
TI  - Evolution of bitter taste receptors in humans and apes.
AB  - Bitter taste perception is crucial for the survival of organisms because it
      enables them to avoid the ingestion of potentially harmful substances. Bitter
      taste receptors are encoded by a gene family that in humans has been shown to
      contain 25 putatively functional genes and 8 pseudogenes and in mouse 33
      putatively functional genes and 3 pseudogenes. Lineage-specific expansions of
      bitter taste receptors have taken place in both mouse and human, but very little
      is known about the evolution of these receptors in primates. We report the
      analysis of the almost complete repertoires of bitter taste receptor genes in
      human, great apes, and two Old World monkeys. As a group, these genes seem to be
      under little selective constraint compared with olfactory receptors and other
      genes in the studied species. However, in contrast to the olfactory receptor gene
      repertoire, where humans have a higher proportion of pseudogenes than apes, there
      is no evidence that the rate of loss of bitter taste receptor genes varies among
      humans and apes.

PMID- 15496550
TI  - Evolution of the AID/APOBEC family of polynucleotide (deoxy)cytidine deaminases.
AB  - The AID/APOBEC family (comprising AID, APOBEC1, APOBEC2, and APOBEC3 subgroups)
      contains members that can deaminate cytidine in RNA and/or DNA and exhibit
      diverse physiological functions (AID and APOBEC3 deaminating DNA to trigger
      pathways in adaptive and innate immunity; APOBEC1 mediating apolipoprotein B RNA
      editing). The founder member APOBEC1, which has been used as a paradigm, is an
      RNA-editing enzyme with proposed antecedents in yeast. Here, we have undertaken
      phylogenetic analysis to glean insight into the primary physiological function of
      the AID/APOBEC family. We find that although the family forms part of a larger
      superfamily of deaminases distributed throughout the biological world, the
      AID/APOBEC family itself is restricted to vertebrates with homologs of AID (a DNA
      deaminase that triggers antibody gene diversification) and of APOBEC2 (unknown
      function) identifiable in sequence databases from bony fish, birds, amphibians,
      and mammals. The cloning of an AID homolog from dogfish reveals that AID extends
      at least as far back as cartilaginous fish. Like mammalian AID, the pufferfish
      AID homolog can trigger deoxycytidine deamination in DNA but, consistent with its
      cold-blooded origin, is thermolabile. The fine specificity of its mutator
      activity and the biased codon usage in pufferfish IgV genes appear broadly
      similar to that of their mammalian counterparts, consistent with a coevolution of
      the antibody mutator and its substrate for the optimal targeting of somatic
      mutation during antibody maturation. By contrast, APOBEC1 and APOBEC3 are later
      evolutionary arrivals with orthologs not found in pufferfish (although synteny
      with mammals is maintained in respect of the flanking loci). We conclude that AID
      and APOBEC2 are likely to be the ancestral members of the AID/APOBEC family
      (going back to the beginning of vertebrate speciation) with both APOBEC1 and
      APOBEC3 being mammal-specific derivatives of AID and a complex set of domain
      shuffling underpinning the expansion and evolution of the primate APOBEC3s.

PMID- 15496551
TI  - How strong is the mutagenicity of recombination in mammals?
AB  - It is commonly believed that a high recombination rate such as that in a
      pseudoautosomal region (PAR) greatly increases the mutation rate because a 170
      fold increase was estimated for the mouse PAR region. However, sequencing PAR and
      non-PAR introns of the Fxy gene in four Mus taxa, we found an increase of only
      twofold to fivefold. Furthermore, analyses of sequence data from human and
      orangutan PAR and X-linked regions and from autosomal regions showed a weak
      effect of recombination on mutation rate (a slope of less than 0.2% per cM/Mb),
      although a much stronger effect on GC content (1% to 2% per cM/Mb). Because
      typical recombination rates in mammals are much lower than those in PARs, the
      mutagenicity of recombination is weak or, at best, moderate, although its effect
      on GC% is much stronger. In addition, contrary to a previous study, we found no
      Fxy duplicate in Mus spretus.

PMID- 15496552
TI  - An exponential core in the heart of the yeast protein interaction network.
AB  - Protein interactions in the budding yeast have been shown to form a scale-free
      network, a feature of other organized networks such as bacterial and archaeal
      metabolism and the World Wide Web. Here, we study the connections established by
      yeast proteins and discover a preferential attachment between essential proteins.
      The essential-essential connections are long ranged and form a subnetwork where
      the giant component includes 97% of these proteins. Unexpectedly, this subnetwork
      displays an exponential connectivity distribution, in sharp contrast to the scale
      free topology of the complete network. Furthermore, the wide phylogenetic extent
      of these core proteins and interactions provides evidence that they represent the
      ancestral state of the yeast protein interaction network. Finally, we propose
      that this core exponential network may represent a generic scaffold around which
      organism-specific and taxon-specific proteins and interactions coalesce.

PMID- 15496553
TI  - Root of the Eukaryota tree as inferred from combined maximum likelihood analyses
      of multiple molecular sequence data.
AB  - Extensive studies aiming to establish the structure and root of the Eukaryota
      tree by phylogenetic analyses of molecular sequences have thus far not resulted
      in a generally accepted tree. To re-examine the eukaryotic phylogeny using
      alternative genes, and to obtain a more robust inference for the root of the tree
      as well as the relationship among major eukaryotic groups, we sequenced the genes
      encoding isoleucyl-tRNA and valyl-tRNA synthetases, cytosolic-type heat shock
      protein 90, and the largest subunit of RNA polymerase II from several protists.
      Combined maximum likelihood analyses of 22 protein-coding genes including the
      above four genes clearly demonstrated that Diplomonadida and Parabasala shared a
      common ancestor in the rooted tree of Eukaryota, but only when the fast-evolving
      sites were excluded from the original data sets. The combined analyses, together
      with recent findings on the distribution of a fused dihydrofolate reductase
      thymidylate synthetase gene, narrowed the possible position of the root of the
      Eukaryota tree on the branch leading to Opisthokonta or to the common ancestor of
      Diplomonadida/Parabasala. However, the analyses did not agree with the position
      of the root located on the common ancestor of Opisthokonta and Amoebozoa, which
      was argued by Stechmann and Cavalier-Smith [Curr. Biol. 13:R665-666, 2003] based
      on the presence or absence of a three-gene fusion of the pyrimidine biosynthetic
      pathway: carbamoyl-phosphate synthetase II, dihydroorotase, and aspartate
      carbamoyltransferase. The presence of the three-gene fusion recently found in the
      Cyanidioschyzon merolae (Rhodophyta) genome sequence data supported our analyses
      against the Stechmann and Cavalier-Smith-rooting in 2003.

PMID- 15496554
TI  - Isolation and molecular evolution of the selenocysteine tRNA (Cf TRSP) and RNase
      P RNA (Cf RPPH1) genes in the dog family, Canidae.
AB  - In an effort to identify rapidly evolving nuclear sequences useful for
      phylogenetic analyses of closely related species, we isolated two genes
      transcribed by RNA polymerase III (pol III), the selenocysteine tRNA gene (TRSP)
      and an RNase P RNA (RPPH1) gene from the domestic dog (Canis familiaris). We
      focus on genes transcribed by pol III because their coding regions are small
      (generally 100-300 base pairs [bp]) and their essential promoter elements are
      located within a couple of hundred bps upstream of the coding region. Therefore,
      we predicted that regions flanking the coding region and outside of the promoter
      elements would be free of constraint and would evolve rapidly. We amplified TRSP
      from 23 canids and RPPH1 from 12 canids and analyzed the molecular evolution of
      these genes and their utility as phylogenetic markers for resolving relationships
      among species in Canidae. We compared the rate of evolution of the gene-flanking
      regions to other noncoding regions of nuclear DNA (introns) and to the
      mitochondrial encoded COII gene. Alignment of TRSP from 23 canids revealed that
      regions directly adjacent to the coding region display high sequence variability.
      We discuss this pattern in terms of functional mechanisms of transcription.
      Although the flanking regions evolve no faster than introns, both genes were
      found to be useful phylogenetic markers, in part, because of the synapomorphic
      indels found in the flanking regions. Gene trees generated from the TRSP and
      RPPH1 loci were generally in agreement with the published mtDNA phylogeny and are
      the first phylogeny of Canidae based on nuclear sequences.

PMID- 15496555
TI  - Evolutionary history of chromosome 20.
AB  - The evolutionary history of human chromosome 20 in primates was investigated
      using a panel of human BAC/PAC probes spaced along the chromosome.
      Oligonucleotide primers derived from the sequence of each human clone were used
      to screen horse, cat, pig, and black lemur BAC libraries to assemble, for each
      species, a panel of probes mapping to chromosomal loci orthologous to the loci
      encompassed by the human BACs. This approach facilitated marker-order comparison
      aimed at defining marker arrangement in primate ancestor. To this goal, we also
      took advantage of the mouse and rat draft sequences. The almost perfect
      colinearity of chromosome 20 sequence in humans and mouse could be interpreted as
      evidence that their form was ancestral to primates. Contrary to this view, we
      found that horse, macaque, and two New World monkeys share the same marker-order
      arrangement from which the human and mouse forms can be derived, assuming similar
      but distinct inversions that fully account for the small difference in marker
      arrangement between humans and mouse. The evolutionary history of this chromosome
      unveiled also two centromere repositioning events in New World monkey species.

PMID- 15496556
TI  - Molecular phylogeny of the plant pathogenic genus Botrytis and the evolution of
      host specificity.
AB  - The cosmopolitan genus Botrytis contains 22 recognized species and one hybrid.
      The current classification is largely based on morphological characters and, to a
      minor extent, on physiology and host range. In this study, a classification of
      the genus was constructed based on DNA sequence data of three nuclear protein
      coding genes (RPB2, G3PDH, and HSP60) and compared with the traditional
      classification. Sexual reproduction and the host range, important fitness traits,
      were traced in the tree and used for the identification of major evolutionary
      events during speciation. The phylogenetic analysis corroborated the classical
      species delineation. In addition, the hybrid status of B. allii (B. byssoidea x
      B. aclada) was confirmed. Both individual gene trees and combined trees show that
      the genus Botrytis can be divided into two clades, radiating after the separation
      of Botrytis from other Sclerotiniaceae genera. Clade 1 contains four species that
      all colonize exclusively eudicot hosts, whereas clade 2 contains 18 species that
      are pathogenic on either eudicot (3) or monocot (15) hosts. A comparison of
      Botrytis and angiosperm phylogenies shows that cospeciation of pathogens and
      their hosts have not occurred during their respective evolution. Rather, we
      propose that host shifts have occurred during Botrytis speciation, possibly by
      the acquisition of novel pathogenicity factors. Loss of sexual reproduction has
      occurred at least three times and is supposed to be a consequence of negative
      selection.

PMID- 15496557
TI  - Molecular evolution and phylogenetic utility of the petD group II intron: a case
      study in basal angiosperms.
AB  - Sequences of spacers and group I introns in plant chloroplast genomes have
      recently been shown to be very effective in phylogenetic reconstruction at higher
      taxonomic levels and not only for inferring relationships among species. Group II
      introns, being more frequent in those genomes than group I introns, may be
      further promising markers. Because group II introns are structurally constrained,
      we assumed that sequences of a group II intron should be alignable across seed
      plants. We designed universal amplification primers for the petD intron and
      sequenced this intron in a representative selection of 47 angiosperms and three
      gymnosperms. Our sampling of taxa is the most representative of major seed plant
      lineages to date for group II introns. Through differential analysis of
      structural partitions, we studied patterns of molecular evolution and their
      contribution to phylogenetic signal. Nonpairing stretches (loops, bulges, and
      interhelical nucleotides) were considerably more variable in both substitutions
      and indels than in helical elements. Differences among the domains are basically
      a function of their structural composition. After the exclusion of four
      mutational hotspots accounting for less than 18% of sequence length, which are
      located in loops of domains I and IV, all sequences could be aligned
      unambiguously across seed plants. Microstructural changes predominantly occurred
      in loop regions and are mostly simple sequence repeats. An indel matrix
      comprising 241 characters revealed microstructural changes to be of lower
      homoplasy than are substitutions. In showing Amborella first branching and
      providing support for a magnoliid clade through a synapomorphic indel, the petD
      data set proved effective in testing between alternative hypotheses on the basal
      nodes of the angiosperm tree. Within angiosperms, group II introns offer
      phylogenetic signal that is intermediate in information content between that of
      spacers and group I introns on the one hand and coding sequences on the other.

PMID- 15496558
TI  - Cystic kidney diseases: learning from animal models.

PMID- 15496559
TI  - Renal cysts and diabetes syndrome resulting from mutations in hepatocyte nuclear
      factor-1beta.

PMID- 15496560
TI  - The prognostic impact of fluctuating levels of C-reactive protein in Brazilian
      haemodialysis patients: a prospective study.
AB  - BACKGROUND: A single elevated C-reactive protein (CRP) value predicts mortality
      in haemodialysis (HD) patients, but the relative importance of repeated vs
      occasional positive systemic inflammatory response findings is not known.
      METHODS: To assess the influence on survival of occasional inflammation, CRP,
      serum albumin (S-Alb) and fibrinogen were analysed bimonthly in 180 HD patients
      (54% male, 49+/-14 years). Clinically significant inflammation was defined as CRP
      >5.1 mg/l, based on the receiver operating characteristics curve for CRP as
      predictor of death. Based on four consecutive measurements of CRP, patients were
      assigned into three groups: group 1 (n = 74; 41%), no inflammation (CRP < or =
      5.1 mg/l in all measurements); group 2 (n = 65; 36%), occasional inflammation (1
      3 measurements of CRP > 5.1 mg/l); and group 3 (n = 41; 23%), persistent
      inflammation (all measurements of CRP >5.1 mg/l). The nutritional status was
      evaluated by subjective global assessment (SGA) and body mass index (BMI), and
      the survival (21 months of follow-up) by Kaplan-Meier curve and Cox model.
      RESULTS: The median and range of CRP values (mg/l) for group 1, 2 and 3 were: 3.2
      (3.2-5.1), 3.6 (3.2-54.9) and 13.8 (5.2-82), respectively (P<0.001), whereas the
      prevalence of malnutrition, assessed by SGA and BMI, did not differ significantly
      between the groups. The survival rate by Kaplan-Meier analysis was significantly
      different among the groups (chi2 = 12.34; P = 0.0004). Patients in group 3 showed
      the highest mortality (34%; P = 0.001), compared with group 1 (8%) and group 2
      (14%; P = 0.01), respectively, whereas there was no significant difference in
      mortality between groups 1 and 2. Age, CRP, S-Alb level and SGA were independent
      predictors of mortality. CONCLUSION: The patients with a persistent elevation of
      CRP had a higher mortality rate than the patients with occasional CRP elevation.
      Thus, persistent, rather than occasional, inflammation is an important predictor
      of death in HD patients.

PMID- 15496561
TI  - Time course of low molecular weight proteins in the early kidney transplantation
      period--influence of corticosteroids.
AB  - BACKGROUND: Cystatin C (Cys C) is an established new marker of renal function in
      patients with various renal diseases and in kidney transplantation. However, few
      data are available for the early post-transplantation period. METHODS: Twenty-two
      patients who underwent renal transplantation (RTx) were evaluated for the
      kinetics of Cys C from day 0 to 14 in relation to creatinine and beta-2
      microglobulin (B2MG). Blood samples were obtained immediately before and after
      transplantation and on a daily basis thereafter. Serum levels before
      transplantation (100%) were used to calculate reduction ratios. RESULTS: The
      decrease of the analytes differed considerably: immediately after RTx Cys C
      declined by 27.3% (P < 0.01). However, after 3 days, on average, all patients
      showed a significant increase in Cys C levels (15+/-2.5%; P < 0.01). B2MG levels
      fell quickly by 55.4 and 73.8% after days 1 and 7, respectively, and remained
      stable thereafter. In contrast, creatinine did not decrease immediately after RTx
      but fell slowly by 67.5% at the end of the study. Prior to rejection, all
      analytes showed a similar behaviour. Rejection treatment with high-dose
      methylprednisolone induced a significant increase in Cys C (+22.8+/-7.9%, P <
      0.05), while in parallel, creatinine and B2MG decreased (-12.9+/-3.4 and -8.4+/
      6.89%). CONCLUSIONS: Corticosteroid treatment for induction of immunosuppression
      or rejection therapy significantly induces Cys C, but decreases B2MG. Cys C and
      B2MG are not helpful in establishing the diagnosis of rejection earlier. Thus,
      our data indicate that Cys C and B2MG testing does not accurately reflect changes
      in the glomerular filtration rate early after transplantation.

PMID- 15496562
TI  - Mycophenolate mofetil vs azathioprine in a large population of elderly renal
      transplant patients.
AB  - BACKGROUND: Mycophenolate mofetil (MMF) has been shown to decrease acute
      rejection episodes after kidney transplantation, and has been associated with
      better graft and patient survival vs azathioprine (AZA). Previous studies
      reported a higher risk of death due to infection in elderly recipients treated
      with MMF-based immunosuppression. METHODS: We analysed 5069 elderly ( > 65 years
      of age) primary renal allograft recipients treated with either MMF or AZA
      reported to the Scientific Registry of Transplant Recipients between 1988 and
      2000, and compared rates of acute rejection, late acute rejection, graft
      survival, death-censored graft survival, patient survival and death with a
      functioning graft. RESULTS: In Cox proportional hazard models, MMF was associated
      with lower rates of late acute rejection with 12 (RR = 0.72, P = 0.11) and 24
      months (RR = 0.50, P = 0.028) of continuous therapy. In univariate analysis
      (Kaplan-Meier), MMF was associated with improved patient (P = 0.0003) and graft
      (P<0.0001) survival vs AZA, and trends toward improved patient and graft survival
      in multivariate analyses. CONCLUSIONS: These findings demonstrate the efficacy of
      MMF-based immunosuppression in elderly transplant recipients and do not suggest
      an increased risk of death compared to treatment with AZA.

PMID- 15496563
TI  - Epithelial cell polarity and improved early outcomes in delayed graft function: a
      pilot study of polyclonal vs monoclonal antibodies.
AB  - BACKGROUND: Polyclonal antibody preparations contain antibodies that bind not
      only to molecules on circulating lymphocytes but also to other sites that bear
      similar antigens. We hypothesized that this extra-antibody effect would increase
      the number of intact tubular epithelial cells in organs at high risk for delayed
      graft function (DGF). METHODS: We used immunohistochemistry to examine serial
      biopsy samples (time 0 and 7-10 days after transplantation) in 18 kidney
      transplant recipients with DGF. These individuals received either polyclonal
      rabbit antithymocyte sera or a monoclonal humanized anti-CD25 antibody as
      induction immunosuppression. We also examined their early clinical course over 6
      months. RESULTS: Individuals treated with the polyclonal preparation demonstrated
      greater preservation of kidney epithelial cell polarity manifested by more
      intense and more localized basolateral distribution of E-cadherin (P = 0.016),
      beta-catenin (P = 0.008) and Na-K ATPase (P = 0.02). These individuals were also
      more likely to maintain greater estimated glomerular filtration rates (eGFRs) at
      follow-up than patients treated with an anti-CD25 monoclonal antibody (6 month
      eGFR polyclonal: 55.5+/-7.12 ml/min vs monoclonal: 43.33+/-6.48 ml/min; P =
      0.002). CONCLUSION: Though a pilot study, these data suggest that a purified
      polyclonal antibody preparation may help conserve functional kidney mass during
      DGF with potential benefits on transplant function overall.

PMID- 15496564
TI  - A novel SGLT2 mutation in a patient with autosomal recessive renal glucosuria.

PMID- 15496565
TI  - An immunosuppressed patient with systemic vasculitis suffering from cerebral
      abscesses due to Nocardia farcinica identified by 16S rRNA gene universal PCR.

PMID- 15496566
TI  - Re-challenging patients who developed pure red cell aplasia with epoetin: can it
      be done?

PMID- 15496567
TI  - Sirolimus and angiotensin-converting enzyme inhibitors together induce tongue
      oedema in renal transplant recipients.

PMID- 15496568
TI  - Vasculitis and kidney involvement in pregnancy: evidence-based medicine and
      ethics bear upon clinical choices.

PMID- 15496569
TI  - Malignant hypertension after adrenalectomy.

PMID- 15496570
TI  - An expensive multifactorial renal failure.

PMID- 15496571
TI  - Obstructive uropathy associated with bilateral renal lymphangiomatosis.

PMID- 15496572
TI  - Recurrent secondary hyperparathyroidism and calciphylaxis due to a retro
      oesophageal gland.

PMID- 15496573
TI  - Is the afferent arteriole the main location of nitric oxide action and synthesis
      in humans?

PMID- 15496574
TI  - Some notes about the usage of the Charlson co-morbidity index.

PMID- 15496575
TI  - Severe bladder dysfunction in a family with ADH receptor gene mutation
      responsible for X-linked nephrogenic diabetes insipidus.

PMID- 15496576
TI  - Conflict of interest.

PMID- 15496577
TI  - A fatal case of aluminium encephalopathy in a patient with severe chronic renal
      failure not on dialysis.

PMID- 15496578
TI  - Hypercalcaemia from non-prescription vitamin A.

PMID- 15496579
TI  - Old-time features are back in renal transplanted patients.

PMID- 15496580
TI  - Sirolimus-induced pneumonitis, sinusitis and macular oedema.

PMID- 15496581
TI  - Physiological roles of SAPK/JNK signaling pathway.
AB  - Stress-activated protein kinase/c-Jun NH(2)-terminal kinase (SAPK/JNK) is
      activated by many types of cellular stresses and extracellular signals. Recent
      studies, including the analysis with knockout mice, have led to progress towards
      understanding the physiological roles of SAPK/JNK activation in embryonic
      development in addition to immune responses. SAPK/JNK activation plays essential
      roles in organogenesis during mouse development by regulating cell survival,
      apoptosis, and proliferation. Two SAPK/JNK activators, SEK1 and MKK7, are
      required for fetal liver formation and full activation of SAPK/JNK, which
      responds to various stimuli in an all-or-none manner. This article focuses on
      physiological roles of SAPK/JNK activation in fetal liver formation and in
      apoptosis regulation.

PMID- 15496582
TI  - A MAP kinase cascade that controls plant cytokinesis.
AB  - Several components of mitogen-activated protein kinase (MAPK) cascades have been
      identified in higher plants and have been implicated in cellular responses to a
      wide variety of abiotic and biotic stimuli. Our recent work has demonstrated that
      a MAP kinase cascade is involved in the regulation of cytokinesis in plant cells.
      The MAP kinase cascade in tobacco includes NPK1 MAPK kinase kinase, NQK1 MAPK
      kinase, and NRK1 MAPK, and its activation is triggered by the binding of NACK1/2
      kinesin-like protein to the NPK1 MAPK kinase kinase at the late M-phase of the
      cell cycle. We refer to this cascade as the NACK-PQR pathway. In this review, we
      introduce a mechanism for the regulation of plant cytokinesis, focusing on the
      role of the NACK-PQR pathway.

PMID- 15496583
TI  - Ribozymes: applications to functional analysis and gene discovery.
AB  - Ribozymes are catalytic RNA molecules that cleave RNAs with high specificity.
      Since the discovery of these non-protein enzymes, the rapidly developing field of
      ribozymes has been of particular interest because of the potential utility of
      ribozymes as tools for reversed genetics. However, despite extensive efforts, the
      activity of ribozymes in vivo has not usually been high enough to achieve the
      desirable biological effects. Now, by the use of RNA polymerase III (pol III)
      promoters, the ribozyme activity in cells has been successfully improved by
      developing efficient transport systems for the transcripts to the cytoplasm. In
      addition, it is possible to cleave a specific target RNA in cells by using an
      allosterically controllable ribozyme or an RNA-protein hybrid ribozyme. These
      ribozymes are potentially applicable to molecular gene therapy and efficient gene
      discovery systems. Furthermore, the developed pol III expression system is
      applicable to the expression of small interfering RNAs (siRNAs). The advantage of
      such ribozymes over siRNAs is the high specificity of the ribozyme that would not
      cause interferon responses.

PMID- 15496584
TI  - A picoliter chamber array for cell-free protein synthesis.
AB  - The completion of human genome sequencing has shifted the focus of research from
      genes to proteins. In this regard, a protein library chip has become a useful
      tool for cell-free protein synthesis. In this study, we attempted to make a
      highly-integrated protein chip from a DNA library using in vitro protein
      synthesis on a microchamber array fabricated by using PDMS (polydimethyl
      siloxane), a hydrophobic surface, and glass, a hydrophilic bottom substrate.
      These structural properties prevented cross-contamination among the chambers. The
      minimum volume capacity of the smallest chamber was about 1 pl. The total number
      of chambers per chip was 10,000 on one chip (capacity 150 pl) and 250,000 on two
      others (1 and 5 pl). Next, we attempted in vitro protein synthesis using this
      microchamber array. The fluorescence of Green Fluorescent Protein (GFP) expressed
      on the chamber was rapidly detected (within just 1 h). GFP expression was also
      successful using immobilized DNA molecules on polymer beads. DNA immobilized
      beads were added as the source to each microchamber. Protein was successfully
      synthesized from DNA immobilized beads, which allowed easy handling of the DNA
      molecules.

PMID- 15496585
TI  - Conformational difference in HMGB1 proteins of human neutrophils and lymphocytes
      revealed by epitope mapping of a monoclonal antibody.
AB  - HMGB1 and HMGB2 are abundant nonhistone chromosomal proteins in eukaryotic
      organisms. Their respective primary sequences are highly conserved. Our previous
      studies showed that these proteins are novel autoantigens of anti-neutrophil
      cytoplasmic antibodies in sera from patients with ulcerative colitis (UC),
      rheumatic disease and autoimmune hepatitis (AIH). In the present paper, we showed
      that anti-HMGB1 and HMGB2 antibodies in sera of patients with UC do not recognize
      HMGB1 in neutrophils while they recognize the protein in lymphocytes. Anti-HMGB2
      monoclonal antibody FBH7, recognizing HMGB1 in lymphocytes, showed a similar
      profile to the antibodies in the patients' sera. In order to elucidate the
      difference in immunoreactivity to HMGB1 between neutrophils and lymphocytes, we
      mapped the epitope for FBH7 by means of several methods. The results showed that
      FBH7 recognizes the intact conformation composed of 52-56 residues of HMGB1 in
      lymphocytes. This suggested that HMGB1 in neutrophils is conformationally changed
      in the epitope or the peripheral structure of the epitope from the protein in
      lymphocytes. The apparent conformational change of HMGB1 between neutrophils and
      lymphocytes will be important for understanding the functional difference of
      HMGB1 in these cells.

PMID- 15496586
TI  - Importance of exposed aromatic residues in chitinase B from Serratia marcescens
      2170 for crystalline chitin hydrolysis.
AB  - Chitinase B (ChiB) of S. marcescens has five exposed aromatic residues linearly
      aligned toward the catalytic cleft, Tyr481 and Trp479 in the C-terminal domain,
      and Trp252, Tyr240 and Phe190 in the catalytic domain. To determine the
      contribution of these residues to the hydrolysis of crystalline beta-chitin, site
      directed mutagenesis, to replace them by alanine, was carried out. The Y481A,
      W479A, W252A, and Y240A mutations all decreased the binding activity and
      hydrolyzing activity toward beta-chitin microfibrils. Substitution of Trp
      residues affected the binding activity more severely than that of Tyr residues.
      The F190A mutation decreased neither the binding activity nor the hydrolyzing
      activity. None of the mutations decreased the hydrolyzing activity toward soluble
      substrates. These results suggest that ChiB hydrolyzes crystalline beta-chitin
      via a mechanism in which four exposed aromatic residues play important roles,
      similar to the mechanism of hydrolysis by ChiA of this bacterium, although the
      directions of hydrolysis of the two chitinases are opposite.

PMID- 15496587
TI  - HTRP--an immediate-early gene product induced by HSV1 infection in human embryo
      fibroblasts, is involved in cellular co-repressors.
AB  - The interaction between virus and receptor is a process that mimics physiological
      ligand binding receptors and induces signal transduction. In the investigation of
      the interaction between HSV1 (Herpes Simplex virus 1) and human fibroblasts via
      virus binding to its receptor complex on cellular membranes, the HTRP (human
      transcription regulator protein), a protein encoded by an immediate-early gene of
      cellular response against the specific stimulation of HSV1 binding, was cloned
      from a cDNA library established from early gene response mRNA. The localization
      of HTRP expressed as a fusion polypeptide with a fluorescent protein in HeLa
      cells was confirmed to be the nucleus. The results of a yeast two-hybrid
      experiment indicated that HTRP is indeed involved in the interaction with the SAP
      (mSin3-associate polypeptide) complex via SAP30. A pull-down test and Western
      blotting in vitro, and immunoprecipitation in vivo also provided evidence in
      support of this result. The interaction of HTRP with SAP30 in its conserved
      domain implies that this protein family, as the products of immediate-early
      genes, comprise functional molecules involved in the transcriptional regulation
      of cells, which might be related to the inhibition of some cell survival genes.

PMID- 15496588
TI  - Anaerobic treatment of antibiotic production wastewater and kinetic evaluations.
AB  - In this study, the anaerobic treatment of high-strength antibiotic production
      wastewater and the development of a mathematical model for the treatment were
      attempted. Anaerobic treatability was investigated using synthetic solutions and
      original wastewater of which the initial chemical oxygen demand (COD) was
      determined. Initial COD of solutions was increased from 3,000 to 43,000 mg
      O(2)/liter in an anaerobic bioreactor. The bioreactor pH was maintained at 6.5
      7.5. The temperature was kept constant at 37 +/- 1 degrees C. Raw materials and
      original wastewater containing penicillin antibiotics were obtained from Fako
      Pharmaceutical Factory (Fako) in Istanbul, Turkey. Anaerobic sludge used for
      treatment was obtained from Pakmaya Baker's Yeast Producing Factory (Pakmaya) in
      Izmit, Turkey and the Fako. A mathematical model based on substrate (total COD)
      concentration was developed assuming that only three consecutive reactions,
      namely, hydrolysis, acidogenesis and methanogenesis, are significant. From the
      experimental data, a model that can be used for COD calculation as a function of
      time was developed using the first- and the second-order kinetic approaches.
      Making use of the developed model equation, it was proved that the anaerobic
      treatment of high strength (COD > 25,000 mg O(2)/liter) antibiotic production
      wastewater fits the second-order kinetics.

PMID- 15496589
TI  - Identification and characterization of nuclear localization signals of CaMKP-N.
AB  - Calmodulin-dependent protein kinase phosphatase (CaMKP) and CaMKP-N
      dephosphorylate and regulate multifunctional Ca(2+)/calmodulin-dependent protein
      kinases. The enzymatic properties of CaMKP-N and CaMKP resemble each other,
      whereas their localizations are different. CaMKP-N is localized in the nucleus,
      whereas CaMKP is localized in the cytosol. In the present study, the nuclear
      localization signals (NLSs) of CaMKP-N were identified and characterized. CaMKP-N
      contains two NLSs, NLS1 and NLS2, at the C-terminus. A cluster of basic residues
      in the NLSs is important for their function. NLS1 and NLS2 function
      independently, but mutagenesis analysis suggests that these NLSs interact with
      each other.

PMID- 15496590
TI  - Developmental expression of a sialyltransferase responsible for sialylation of
      cortical alveolus glycoprotein during oogenesis in rainbow trout (Oncorhynchus
      mykiss).
AB  - Polysialoglycoprotein (PSGP) is a major cortical alveolus glycoprotein of rainbow
      trout eggs that is characterized by the attachment of a polysialic acid structure
      to its O-glycan chains. It has been demonstrated that the polysialic acid
      structure is synthesized by at least three sialyltransferases mostly localized in
      cortical alveoli. Here we have cloned a cDNA encoding the sialyltransferase,
      designated rtST6GalNAc, responsible for the transfer of the first sialic acid
      residue onto the O-glycan chain of PSGP. This enzyme belongs to the vertebrate
      ST6GalNAc II family, and is strongly expressed in ovaries. Of those O
      glycoproteins tested as substrates, asialo-PSGP is the best substrate. These
      results indicate that rtST6GalNAc is the enzyme responsible for the sialylation
      of PSGP during oogenesis. Furthermore, the rtST6GalNAc mRNA is expressed
      throughout oogenesis, is down-regulated at the late yolk vesicle stage (May), and
      then up-regulated during vitellogenesis (until August). This developmental
      profile is highly similar to that of STL2, a cortical alveolus lectin, while it
      is quite different from that of PSGP, which is extensively expressed at the yolk
      vesicle stage and down-regulated at later stages. Thus, not all cortical alveolus
      components are transcribed concomitantly. This is the first description of a
      developmental change in the transcription of a glycosyltransferase during
      oogenesis.

PMID- 15496591
TI  - Interchangeability and distinct properties of bacterial Fe-S cluster assembly
      systems: functional replacement of the isc and suf operons in Escherichia coli
      with the nifSU-like operon from Helicobacter pylori.
AB  - The assembly of iron-sulfur (Fe-S) clusters, a key step in the post-translational
      maturation of Fe-S proteins, is mediated by a complex apparatus. In E. coli, this
      process involves two independent systems called ISC and SUF encoded by the iscSUA
      hscBA-fdx gene cluster and sufABCDSE operon, respectively. Another system, termed
      NIF (nifSU), is required for the maturation of nitrogenase in nitrogen-fixing
      bacteria. We have developed a novel genetic system to gain further insight into
      these multi-component systems, and to determine how ISC, SUF and NIF might differ
      in their roles in Fe-S assembly. We have constructed an E. coli mutant lacking
      both the isc and suf operons, and this strain can only survive in the presence of
      a complementing plasmid. Using the plasmid replacement technique, we examined the
      isc and suf operons, and identified the genes essential for the function.
      Additionally, we have found that nifSU-like genes cloned from Helicobacter pylori
      are functionally exchangeable with the isc and suf operons. Thus, the NIF-like
      system participates in the maturation of a wide variety of Fe-S proteins. An
      increased ability of NIF to complement isc and suf loss was seen under anaerobic
      conditions. This may explain why the NIF system is only found in a limited number
      of bacterial species, and most other organisms prefer the ISC and/or SUF systems.
      While the differences between ISC and SUF were small with respect to the
      complementing activity, the SUF system appears to be more advantageous for
      bacterial growth in the presence of hydrogen peroxide.

PMID- 15496592
TI  - Purification and characterization of human uroporphyrinogen III synthase
      expressed in Escherichia coli.
AB  - The side-chain asymmetry of physiological porphyrins is produced by the
      cooperative action of hydroxymethylbilane synthase and uroporphyrinogen (uro'gen)
      III synthase. Although the role of uro'gen III synthase is essential for the
      chemistry of porphyrin biosynthesis, many aspects, structural as well as
      mechanical, of uro'gen III synthase have yet to be studied. We report here an
      expression system in Escherichia coli and a purification procedure for human
      uro'gen III synthase. The enzyme in the lysate was unstable, but we found that
      glycerol prevents the activity loss in the lysate. The purified enzyme showed
      remarkable thermostability, particularly when kept in phosphate buffer containing
      DTT or EDTA, indicating that the enzyme activity may depend on its oxidation
      state. Examination of the relationship between the number of Cys residues that
      are accessible to 5,5'-dithiobis(2-nitrobenzoic acid) and the remaining activity
      during heat inactivation showed that a particular Cys residue is involved in
      activity loss. From the crystal structure of human uro'gen III synthase [Mathews
      et al. (2001) EMBO J. 20, 5832-5839], this Cys residue was considered to be
      Cys73, which is buried deep inside the enzyme, suggesting that Cys73 of human
      uro'gen III synthase plays an important role in enzyme activity.

PMID- 15496593
TI  - Biochemical characterization of TT1383 from Thermus thermophilus identifies a
      novel dNTP triphosphohydrolase activity stimulated by dATP and dTTP.
AB  - The HD domain motif is found in a superfamily of proteins in bacteria, archaea
      and eukaryotes. A few of these proteins are known to have metal-dependant
      phosphohydrolase activity, but the others are functionally unknown. Here we have
      characterized an HD domain-containing protein, TT1383, from Thermus thermophilus
      HB8. This protein has sequence similarity to Escherichia coli dGTP
      triphosphohydrolase, however, no dGTP hydrolytic activity was detected. The
      hydrolytic activity of the protein was determined in the presence of more than
      two kinds of deoxyribonucleoside triphosphates (dNTPs), which were hydrolyzed to
      their respective deoxyribonucleosides and triphosphates, and was found to be
      strictly specific for dNTPs in the following order of relative activity: dCTP >
      dGTP > dTTP > dATP. Interestingly, this dNTP triphosphohydrolase (dNTPase)
      activity requires the presence of dATP or dTTP in the dNTP mixture. dADP, dTDP,
      dAMP, and dTMP, which themselves were not hydrolyzed, were nonetheless able to
      stimulate the hydrolysis of dCTP. These results suggest the existence of binding
      sites specific for dATP and dTTP as positive modulators, distinct from the
      dNTPase catalytic site. This is, to our knowledge, the first report of a non
      specific dNTPase that is activated by dNTP itself.

PMID- 15496594
TI  - Role of the heme regulatory motif in the heme-mediated inhibition of
      mitochondrial import of 5-aminolevulinate synthase.
AB  - 5-Aminolevulinate synthase (ALAS) is a mitochondrial enzyme that catalyzes the
      first step of the heme biosynthetic pathway. The mitochondrial import, as well as
      the synthesis, of the nonspecific isoform of ALAS (ALAS1) is regulated by heme
      through a feedback mechanism. A short amino acid sequence, the heme regulatory
      motif (HRM), is known to be involved in the regulatory function of heme. To
      determine the role of the HRM in the heme-regulated transport of the nonspecific
      and erythroid forms of ALAS in vivo, we constructed a series of mutants of rat
      ALAS1, in which the cysteine residues in the three putative HRMs in the N
      terminal region of the enzyme were converted to serine ones by site-directed
      mutagenesis. The wild-type and mutant enzymes were expressed in quail QT6
      fibroblasts through transient transfection, and the mitochondrial import of these
      enzymes was examined in the presence of hemin. Hemin inhibited the mitochondrial
      import of wild-type ALAS1, but this inhibition was reversed on the mutation of
      all three HRMs in the enzyme, indicating that the HRMs are essential for the heme
      mediated inhibition of ALAS1 transport in the cell. By contrast, exogenous hemin
      did not affect the mitochondrial import of the erythroid-specific ALAS isoform
      (ALAS2) under the same experimental conditions. These results may reflect the
      difference in the physiological functions of the two ALAS isoforms.

PMID- 15496595
TI  - Isoosmotic isolation of rat brain synaptic vesicles, some of which contain
      tyrosine hydroxylase.
AB  - Rat brain synaptic vesicles were isoosmotically isolated and examined for Mg(2+)
      ATPase [EC 3.6.1.3.] and tyrosine hydroxylase [EC 1.14.16.2.] associated with the
      synaptic vesicles. Synaptosomes in 0.32 M sucrose were disrupted by freezing and
      thawing treatment, and the cytosol fraction was fractionated on a Sephacryl S-500
      column with a mean exclusion size of 200 nm. Peak I at the void volume was a
      mixture of large vesicular membranes, small amounts of synaptic vesicles and
      coated vesicles, etc. Peak II consisted of non- and granulated synaptic vesicles
      of 35-40 nm diameter, and peak III of soluble proteins. The synaptic vesicles in
      peak II reacted with antibodies against the H(+)-ATPase A-subunit, vesicular
      acetylcholine transporter, and vesicular monoamine transporter. However, they
      showed little Mg(2+)-ATPase activity. Tyrosine hydroxylase was observed in either
      peak II or III on blotting with an anti-tyrosine hydroxylase antibody. These
      results imply that tyrosine hydroxylase exists in soluble and bound forms to
      synaptic vesicles in nerve terminals.

PMID- 15496596
TI  - Effect of forskolin on synaptotagmin IV protein trafficking in PC12 cells.
AB  - Synaptotagmin IV (Syt IV) was originally described as an immediate early gene
      product induced by forskolin or membrane depolarization in PC12 cells; however,
      nothing is known about the subcellular localization and transport of the newly
      translated Syt IV protein in PC12 cells. In this study, we investigated the
      transport mechanism of Syt IV protein induced by forskolin and found that
      forskolin treatment dramatically increases the Syt IV protein level
      (approximately 10-fold, to a level comparable to that of Syt IX) and promotes the
      transport of Syt IV protein from the Golgi to the cell periphery by a microtubule
      dependent motor(s). The expression levels and subcellular localizations of two
      major Syt isoforms (I and IX) in PC12 cells, on the other hand, were unaffected
      by such treatment. Immunoelectron microscopic analysis showed that some Syt IV
      signals are clearly associated with dense-core vesicles in forskolin-treated PC12
      cells, although the majority of the Syt IV molecules at the cell periphery were
      present on clear vesicular structures other than dense-core vesicles. An N
      terminal antibody-uptake experiment indicated that Syt IV-containing vesicles in
      forskolin-treated PC12 cells undergo Ca(2+)-dependent exocytosis, because uptake
      of the anti-Syt IV-N antibody from the culture medium was slightly, but
      significantly, increased after forskolin treatment. Our results indicate that
      forskolin (or the increased cAMP level) is important for the transport of the Syt
      IV protein from the Golgi to the cell periphery, but not sufficient for the
      sorting of all Syt IV molecules to mature dense-core vesicles.

PMID- 15496597
TI  - Induction of transient ion channel-like pores in a cancer cell by antibiotic
      peptide.
AB  - The anticancer activity of anti-bacterial cecropins makes them potentially useful
      as peptide anti-cancer drugs. We used the cell-attached patch to study the effect
      of cecropin B (CB; having one hydrophobic and one amphipathic alpha-helix) and
      its derivative, cecropin B3 (CB3; having two hydrophobic alpha-helices) on the
      membrane of Ags cancer cells. Application of 10-60 microM CB onto the membrane of
      the cancer cell produces short outward currents. Comparative study with CB3,
      which induces no outward currents, shows that the amphipathic group of CB is
      necessary for the pore formation. The results provide a rationale to study the
      cell-killing activity of antimicrobial peptides at the single cancer cell level.

PMID- 15496598
TI  - Vasectomy techniques for male sterilization: systematic Cochrane review of
      randomized controlled trials and controlled clinical trials.
AB  - BACKGROUND: The review aimed to compare the effectiveness, safety and
      acceptability of vasectomy techniques for male sterilization. METHODS: We
      searched five computerized databases and reference lists of relevant articles and
      book chapters for randomized controlled trials (RCTs) and controlled clinical
      trials (CCTs) comparing vasectomy techniques. Two reviewers independently
      extracted data from eligible articles. RESULTS: Two poor-quality trials compared
      vas occlusion with clips versus a conventional technique, and four poor-quality
      trials examined vas irrigation with water versus no irrigation or irrigation with
      euflavine. No significant differences regarding the primary outcome of time to
      azoospermia were found. However, one trial reported fewer median number of
      ejaculations to azoospermia with euflavine rather than water irrigation. An
      interim report of a high-quality trial comparing vasectomy with and without
      fascial interposition found more azoospermia with fascial interposition but also
      more surgical difficulties. CONCLUSIONS: No conclusions can be reached regarding
      the effectiveness, safety and acceptability of vas occlusion techniques or vas
      irrigation since only low-quality, underpowered studies were available. Fascial
      interposition had improved vasectomy success but also increased surgical
      difficulty. High-quality, adequately reported RCTs are required. More work is
      also needed in the standardization of follow-up protocols, evaluation of
      vasectomy success and failure, recanalization and analytical methods.

PMID- 15496599
TI  - Multiple births: does the news media influence public perceptions?

PMID- 15496600
TI  - Live birth with sperm cryopreserved for 21 years.

PMID- 15496601
TI  - Are laparoscopic ovarian diathermy and gonadotropin administration the only
      therapeutic second-steps in clomiphene-citrate resistant women with polycystic
      ovary syndrome?

PMID- 15496602
TI  - Mechanisms regulating the expression of indoleamine 2,3-dioxygenase during
      decidualization of human endometrium.

PMID- 15496603
TI  - Effect of dietary ribonucleotides on infant immune status. Part 2: Immune cell
      development.
AB  - The objective of this study was to determine whether dietary ribonucleotides
      alter immune cell phenotypes or function in the first year of life. Newborn term
      infants in a double-blind, 12-mo, multicenter trial were randomized to cow milk
      formula groups with (FN, n = 138) or without (F, n = 147) 72 mg/L supplemental
      ribonucleotides. A nonrandomized HMF cohort (n = 192) was concurrently enrolled.
      Eighty-eight immune blood cell types were characterized by flow cytometry. Data
      were analyzed by multivariate ANOVA (MANOVA), ANOVA, and repeated measures
      analysis (RMA), with adjustments made for multiple comparisons. Ribonucleotide
      feeding changed subpopulations of T and natural killer (NK) cells. FN had higher
      numbers and percentages of memory/effector (M/E) cytotoxic/suppressor
      (CD45R0(+)CD8(+), RMA) T, Fas(+) M/E (CD45R0(+)CD95(+)CD3(+), 6 mo) T, and
      CD56(+)CD16(-) NK cells (CD56(+)CD16(-)CD3(-)CD8(-), 12 mo), and higher
      percentages of M/E helper (CD45R0(+)CD4(+), RMA) T, Tc1 (IFN gamma(+)CD4(
      )CD3(+), RMA), total interferon (IFN)gamma T (IFN gamma(+)CD4(+/-)CD3(+), RMA),
      Th2 (IL-4(+)CD4(+)CD3(+), 7 mo), and CD57(+) NK-T cells (CD57(+)CD56(-)CD3(+), 6
      mo, 7 mo) compared with F. Percentages of naive helper T (CD45RA(+)CD4(+), 12 mo)
      and numbers and percentages of CD56(+) NK-T cells (CD56(+)CD16(-)CD3(+)CD8(-), 2
      mo, 6 mo) were lower in FN than F. Percentages of M/E cytotoxic/suppressor, Th2,
      and CD56(+)CD16(-) NK cells in FN were significantly higher than F but were not
      different from HMF, whereas F was significantly lower than HMF. Ribonucleotide
      supplementation of infant formula supported increased T-cell maturation and
      affected immunoregulatory NK cell subsets. These FN-associated immune cell
      profiles either did not differ from those infants fed HMF or tended to be more
      like those fed HMF than those fed F.

PMID- 15496605
TI  - Dysfunction of pulmonary surfactant in chronically ventilated premature infants.
AB  - Infants of <30 wk gestation often require respiratory support for several weeks
      and may develop bronchopulmonary dysplasia (BPD), which is associated with long
      term pulmonary disability or death in severe cases. To examine the status of
      surfactant in infants at high risk for BPD, this prospective study analyzed 247
      tracheal aspirate samples from 68 infants of 23-30 wk gestation who remained
      intubated for 7-84 d. Seventy-five percent of the infants had one or more
      surfactant samples with abnormal function (minimum surface tension 5.1-21.7 mN/m
      by pulsating bubble surfactometer), which were temporally associated with
      episodes of infection (p = 0.01) and respiratory deterioration (p = 0.005).
      Comparing normal and abnormal surfactant samples, there were no differences in
      amount of surfactant phospholipid, normalized to total protein that was recovered
      from tracheal aspirate, or in relative content of phosphatidylcholine and
      phosphatidylglycerol. Contents of surfactant proteins (SP) A, B, and C, measured
      in the surfactant pellet by immunoassay, were reduced by 50%, 80%, and 72%,
      respectively, in samples with abnormal surface tension (p < or = 0.001). On
      multivariable analysis of all samples, SP-B content (r = -0.58, p < 0.0001) and
      SP-C content (r = -0.32, p < 0.001) were correlated with surfactant function. We
      conclude that most premature infants requiring continued respiratory support
      after 7 d of age experience transient episodes of dysfunctional surfactant that
      are associated with a deficiency of SP-B and SP-C.

PMID- 15496604
TI  - Effect of dietary ribonucleotides on infant immune status. Part 1: Humoral
      responses.
AB  - The objective of this study was to further explore previously identified effects
      of supplemental ribonucleotides on infant immune status as measured by antibody
      responses to routine infant immunizations. Infants were randomized to a milk
      based formula with (FN, n = 138) or without (F, n = 147) 72 mg ribonucleotides/L.
      A cohort of human milk-fed (HMF, n = 192) infants was also followed. Subjects
      were given Haemophilus influenzae type b (Hib), diphtheria tetanus acellular
      pertussis, and oral poliovirus vaccinations at 2, 4, and 6 mo of age, and
      specific antibody responses were assessed at 2, 6, 7, and 12 mo. Growth and
      safety data were also monitored. Using a two-group repeated measures analysis
      (RMA), FN-fed infants had significantly higher poliovirus type 1 neutralizing
      antibody (PV-VN1) responses than F-fed infants (p = 0.045). Using three-group
      RMA, PV-VN1 responses in HMF infants were not different from FN-fed infants,
      while HMF-fed infant PV-VN1 responses were significantly higher than F-fed
      infants at 6 (p = 0.0004) and 12 mo (p = 0.0001). FN-fed infants had responses to
      Hib Farr, diphtheria, tetanus toxoid, oral poliovirus-specific IgA, and PV-VN3
      not significantly different from those of F and HMF infants. Growth,
      gastrointestinal tolerance, and adverse events were equivalent among the three
      groups. The FN-associated increase in PV-VN1 response and nonstatistically
      significant trends toward increased Hib and diphtheria antibody responses were
      consistent with observations from earlier studies, indicating immune benefits of
      nucleotide supplementation of infant formula.

PMID- 15496606
TI  - Fic1 is expressed at apical membranes of different epithelial cells in the
      digestive tract and is induced in the small intestine during postnatal
      development of mice.
AB  - Mutations in ATP8B1 are associated with FIC1 disease, an autosomal recessive
      disorder in which intrahepatic cholestasis is the predominant manifestation.
      ATP8B1 encodes FIC1, which is expressed in several tissues, most prominently in
      the intestine, pancreas, and stomach and, to a much lesser extent, in the liver.
      In this study, Fic1 localization and expression during postnatal development was
      examined in healthy mice. Immunoblot and RT-PCR analysis indicated Fic1 is
      expressed abundantly in regions of the adult gastrointestinal tract of humans and
      mice. Immunohistochemistry revealed that Fic1 was localized to the apical
      membranes of enterocytes, pancreatic acinar cells, gastric pit epithelial cells,
      and hepatocytes and cholangiocytes. Subsequent analysis of early postnatal
      expression revealed that Fic1 expression in the small intestine was limited or
      absent at the age of 7 and 14 d and increased significantly with maturation. In
      contrast, pancreatic, hepatic, and gastric Fic1 expression was not diminished
      during the first 3 wk of postnatal development. In conclusion, these data show
      that Fic1 is expressed in a tissue-specific and developmentally regulated fashion
      at the apical membranes of epithelial cells. We speculate that the developing
      bile salt pool in the maturing intestine accounts for the increase in Fic1
      protein expression in this tissue.

PMID- 15496607
TI  - Patients homozygous for the T435N mutation of succinyl-CoA:3-ketoacid CoA
      Transferase (SCOT) do not show permanent ketosis.
AB  - Succinyl-CoA:3-ketoacid CoA transferase (SCOT; locus symbol OXCT; E.C. 2.8.3.5)
      is the main determinant of the ketolytic capacity of tissues. Hereditary SCOT
      deficiency causes episodic ketoacidosis. Permanent ketosis has been regarded as a
      pathognomonic feature of SCOT deficiency. There are three SCOT-deficient patients
      from a small region in Japan and they have not manifested permanent ketosis, even
      though their ketoacidotic crises were as severe as those of other SCOT-deficient
      patients. All three were homozygous for the T435N mutation. Transient expression
      analysis of wild-type and mutant cDNA showed that the T435N mutant retained
      significant residual SCOT activities (20% for that of the wild-type at 39.5
      degrees C, 25% at 37 degrees C, and 50% at 30 degrees C). The difference of
      residual SCOT activities at these temperatures in expression analyses was due to
      differences in the level of the mutant protein. SCOT activity of the T435N
      protein was more vulnerable than the wild-type to heat treatment at 42 degrees C
      and 55 degrees C. These temperature-sensitive characteristics of the mutant
      protein may explain, in part, why the patients developed ketoacidotic crises
      during febrile illness. In SCOT-deficient patients retaining some residual
      activity, permanent ketosis may be absent.

PMID- 15496608
TI  - Altered protein kinase C activation associated with rat embryonic
      dysmorphogenesis.
AB  - It has been suggested that protein kinase C (PKC) is involved in the etiology of
      diabetic complications. The aim of the present study was to investigate the
      putative involvement of different PKC isoforms (alpha, beta1, beta 2, gamma,
      delta, epsilon, and zeta) in the embryopathy of diabetic rat pregnancy. Embryos
      were collected from normal and diabetic rats and assayed for PKC activity, PKC
      mRNA levels, and PKC protein distribution on gestational d 10 and 11. Embryos of
      diabetic rats showed markers of increased activity of PKC-alpha, PKC-beta1, PKC
      gamma, PKC-delta, and PKC-zeta compared with embryos of normal rats on d 10. In
      addition, the malformed embryos had further increased PKC-gamma, and PKC-delta
      activity markers compared with nonmalformed embryos of diabetic rats on
      gestational d 10. In contrast, maternal diabetes caused only two alterations in
      PKC activity markers on gestational d 11, i.e. both PKC-alpha and PKC-zeta were
      decreased in embryos of diabetic rats. We found increased mRNA levels of PKC-beta
      1 and PKC-zeta on d 10 in embryos of diabetic rats and decreased mRNA levels of
      PKC-gamma on d 11 in embryos of diabetic rats. Malformed embryos from diabetic
      rats showed increased distribution of PKC-beta 1 and PKC-beta 2 protein in the
      tissue compared with nonmalformed embryos from diabetic rats and embryos from
      normal rats. We conclude that diabetic rat embryopathy may be associated with
      increased activity and enhanced tissue distribution of several PKC isoforms in
      early organogenesis.

PMID- 15496609
TI  - Fetal intestinal obstruction induces alteration of enteric nervous system
      development in human intestinal atresia.
AB  - Intestinal motility disorders are a major cause of morbidity after surgical
      repair of intestinal atresia of unknown mechanism. We hypothesized that
      interruption of antenatal peristalsis may disturb the normal development of the
      enteric nervous system. Using a series of neuronal (synaptophysin, neuronal
      nitric oxide synthase, neurofilaments) and nonneuronal markers (glial acidic
      fibrillary protein and c-Kit) and immunohistochemistry, we have defined
      developmental steps of the enteric nervous system in normal intestine (12
      fetuses, 15 children, and 4 adults) and their alterations above and below the
      obstacle in 22 human intestinal atresia compared with age-matched controls.
      Antisynaptophysin antibody revealed the progressive conversion of the myenteric
      plexus from a continuous belt into regularly spaced ganglions during normal fetal
      gut development and, by contrast, the significantly delayed appearance of
      individual neuronal ganglions in the distal segments of atresia (p < 0.05).
      Staging using three other markers for neuronal (neurofilaments and neuronal
      nitric oxide synthase) and nonneuronal cells (glial acidic fibrillary protein)
      confirmed that maturation of the myenteric plexus was significantly delayed below
      atresia (p < 0.01). These results indicate that intestinal atresia impairs the
      development of the enteric nervous system and provide an anatomical substrate for
      the motility disorders observed after surgical repair. They point to the role of
      peristalsis in normal gut development and suggest that stimulation of peristalsis
      might be used to accelerate recovery.

PMID- 15496610
TI  - Interleukin (IL)-1 beta in tracheal aspirates from premature infants induces
      airway epithelial cell IL-8 expression via an NF-kappa B dependent pathway.
AB  - Tracheal aspirate IL-8 concentration and airway epithelial cell IL-8 expression
      are each increased in premature infants undergoing mechanical ventilation. We
      sought to determine the cytokines responsible for IL-8 expression in this
      context. Tracheal aspirates were collected from 18 mechanically ventilated
      premature infants. IL-8 protein abundance was high in tracheal aspirates from
      ventilated premature infants (mean, 5806 +/- 4923 pg/mL). IL-1 alpha (mean, 20 +/
      6 pg/mL), IL-1 beta (mean 67 +/- 46 pg/mL), and tumor necrosis factor (TNF)
      alpha (mean, 8 +/- 2 pg/mL) were also found. Incubation of tracheal aspirates
      with 16HBE14o- human bronchial epithelial cells increased IL-8 protein in both
      cell lysates and supernatants, as well as transcription from the IL-8 promoter.
      Aspirates also induced nuclear factor (NF)-kappa B activation. Mutation of the IL
      8 promoter NF-kappa B site abolished aspirate-induced IL-8 transcription.
      Endotoxin concentrations in the tracheal aspirates were negligible and incapable
      of inducing IL-8 promoter activity. Finally, incubation of tracheal aspirates
      with a neutralizing antibody against IL-1 beta reduced epithelial cell IL-8
      production, whereas neutralizing antibodies against IL-1 alpha and TNF-alpha had
      no effect. We conclude that airway fluid from mechanically ventilated premature
      infants contains soluble factors capable of inducing airway epithelial cell IL-8
      expression via a NF-kappa B-dependent pathway, and that IL-1 beta plays a
      specific role in this process.

PMID- 15496611
TI  - Neonatal encephalopathy: association of cytokines with MR spectroscopy and
      outcome.
AB  - In term neonatal encephalopathy, little is known about the relationship between
      early inflammatory markers, neonatal brain injury, and long-term
      neurodevelopmental outcome. Our goal was to determine whether neonatal serum
      cytokine levels are associated with cerebral metabolism assessed by proton
      magnetic resonance spectroscopy (MRS), with magnetic resonance imaging (MRI)
      abnormalities, and with neurodevelopmental outcome at 30 mo of age. Levels of
      seven cytokines [IL-1 beta, IL-6, IL-8, IL-9, IL-12, IL-13, and tumor necrosis
      factor (TNF)-alpha] were measured in dried neonatal blood by immunoaffinity
      chromatography in a prospective cohort of 62 term newborns at risk of neonatal
      encephalopathy. MR images (n = 61) were scored and lactate/choline and N-acetyl
      aspartate (NAA)/choline were measured by MRS (n = 42) on median day of life 6 in
      the deep gray nuclei (DGN) and in the watershed/cortical zone (WS).
      Neurodevelopmental outcome (n = 54) was considered abnormal if the infant died or
      if cognitive delay and/or functional motor deficit were detected at 30 mo. IL-1
      beta, IL-6, IL-8 and TNF-alpha were significantly associated with lactate/choline
      in the DGN (p = 0.03, 0.02, 0.03, and 0.01 respectively), but not in the WS (all
      p > 0.1). Cytokines were not associated with NAA/choline in any region or with
      MRI scores. Children with abnormal neurodevelopmental outcome had higher neonatal
      levels of IL-1 beta, IL-6, IL-8, and lower levels of IL-12 (p = 0.04, 0.03, 0.01,
      0.03 respectively). Elevated inflammatory cytokines were associated with impaired
      cerebral oxidative metabolism, but not with detectable MRI changes in the
      neonatal period. Understanding the link between elevated cytokines and outcome
      would inform novel strategies of cerebral protection.

PMID- 15496612
TI  - Cholesterol in childhood: friend or foe?: Commentary on the article by Merkens et
      al. on page 726.

PMID- 15496613
TI  - Renal D-amino acid oxidase mediates chiral inversion of N(G)-nitro-D-arginine.
AB  - N(G)-nitro-d-arginine (d-NNA), i.v. injected into rats, produced a pressor
      response, and was presumed to act via chiral inversion into N(G)-nitro-l-arginine
      (l-NNA), an inhibitor of nitric oxide synthase. We examined the possible role of
      renal d-amino acid oxidase (DAAO) in the chiral inversion of d-NNA to l-NNA. In
      pentobarbital-anesthetized rats, l-NNA was detected via capillary
      electrochromatography in the blood immediately after i.v. injection of d-NNA. The
      time course of appearance of l-NNA paralleled the increase in blood pressure
      elicited by d-NNA. Unilateral renal ligation partially, and bilateral ligation
      completely, blocked the pressor response as well as the conversion of d-NNA to l
      NNA. Furthermore, injection into conscious rats of sodium benzoate, a selective
      DAAO inhibitor, completely blocked the pressor response to naive d-NNA, but not
      pressor response to d-NNA preincubated with homogenates of the kidney.
      Homogenates of the kidneys, liver (lesser degree), and brain (much lesser degree)
      converted d-NNA to l-NNA, and the chiral inversion was blocked by the addition of
      benzoate. Moreover, d-NNA chiral inversion correlates with the activity of DAAO.
      Our results reveal a novel pathway of chiral inversion of d-amino acids where the
      renal DAAO plays an essential role that accounts for the biological activity of d
      NNA.

PMID- 15496614
TI  - Considerations for use of recombinant adenoviral vectors: dose effect on hepatic
      cytochromes P450.
AB  - Recombinant adenovirus (Ad) serotype 5 is a vector commonly used for gene
      delivery. Although this vector has a natural tropism for the liver, there is a
      limited understanding of how Ad administration affects one of the primary hepatic
      processes, drug metabolism. The effects of systemic administration of a model
      recombinant adenoviral vector on two hepatic cytochrome P450 (P450) enzymes,
      CYP3A2 and 2C11, were investigated. Sprague-Dawley rats were treated with one of
      six vector doses, ranging from 5.7 x 10(6) to 5.7 x 10(12) virus particles
      (vp)/kg. Hepatic P450 protein expression, catalytic activity, and mRNA levels
      were measured over 14 days. Ad administration (5.7 x 10(10)-5.7 x 10(12) vp/kg)
      reduced CYP3A2 over the duration of the study. Six hours after administration of
      5.7 x 10(12) vp/kg, CYP3A2 activity and mRNA levels were suppressed by 45 and
      65%, respectively (P < or = 0.01). This continued throughout the study with
      levels dropping to 36 and 45% of controls by 14 days, respectively (P < or =
      0.01). A similar trend was detected for CYP2C11 within this dosing range.
      Administration of 5.7 x 10(6), 5.7 x 10(8), and 5.7 x 10(9) vp/kg of Ad
      significantly increased both CYP2C11 protein expression by 86, 71, and 107% and
      activity 110, 118, and 53%, respectively, above those of animals treated with
      saline (P < or = 0.01). These results clearly indicate that a single dose of
      adenovirus significantly alters key drug metabolizing enzymes for an extended
      period of time and should be investigated further in the context of the design
      and implementation of clinical trial protocols.

PMID- 15496615
TI  - The chemoprotective agent N-acetylcysteine blocks cisplatin-induced apoptosis
      through caspase signaling pathway.
AB  - Thiols such as N-acetylcysteine (NAC) are increasingly used in clinical trials of
      platinum chemotherapy as chemoprotectants. NAC can prevent
      cisdiamminedichloroplatinum (cisplatin)-induced ototoxicity, nephrotoxicity, and
      gastrointestinal toxicity; however, the molecular mechanisms of NAC on apoptosis
      and cisplatin cytotoxicity remain unknown. We investigated cisplatin cytotoxicity
      and NAC chemoprotection in human tumor cell lines, as assessed by immunoblotting
      and immunocytochemistry. Cisplatin cytotoxicity was associated with nuclear
      translocation of apoptosis induction factor, expression of the pro-apoptotic Bax
      protein, cleavage of caspases 3 and 9, and cleavage of PARP. NAC administration
      reversed the cytotoxic and apoptotic effects if added concurrent with cisplatin
      or up to 2 h after cisplatin, but chemoprotection was reduced if NAC
      administration was delayed more than 2 h and was minimal by 8 h after cisplatin.
      Expression of tumor suppressor p53 and the cell cycle regulatory protein p21 was
      stimulated within 5 to 10 min by cisplatin in p53-positive LX-1 small cell lung
      carcinoma cells, and this effect was blocked by NAC. In p53-negative SKOV3 cells,
      cisplatin toxicity and NAC chemoprotection remained effective, suggesting that
      chemoprotection may be mediated through both p53-dependent and -independent
      pathways. Specific kinase inhibitors demonstrated that cisplatin induced
      apoptosis through the p38 mitogen-activated protein kinase (MAPK) pathway, not
      the extracellular signal-regulated kinase MAPK pathway. These results show that
      NAC blocks both the death receptor and the mitochondrial apoptotic pathways
      induced by cisplatin. The time course for NAC chemoprotection after cisplatin
      matches our previous in vivo results and provides an opportunity to manipulate
      route and timing to maintain cisplatin antitumor efficacy while protecting
      against chemotherapy side effects.

PMID- 15496616
TI  - Images in clinical medicine. Nontraumatic Clostridium septicum myonecrosis.

PMID- 15496617
TI  - Bankrolling stem-cell research with California dollars.

PMID- 15496618
TI  - Financing Medicare in the next administration.

PMID- 15496619
TI  - Triggering myocardial infarction.

PMID- 15496620
TI  - Tuberculous meningitis.

PMID- 15496621
TI  - Exposure to traffic and the onset of myocardial infarction.
AB  - BACKGROUND: An association between exposure to vehicular traffic in urban areas
      and the exacerbation of cardiovascular disease has been suggested in previous
      studies. This study was designed to assess whether exposure to traffic can
      trigger myocardial infarction. METHODS: We conducted a case-crossover study in
      which cases of myocardial infarction were identified with the use of data from
      the Cooperative Health Research in the Region of Augsburg Myocardial Infarction
      Registry in Augsburg, in southern Germany, for the period from February 1999 to
      July 2001. There were 691 subjects for whom the date and time of the myocardial
      infarction were known who had survived for at least 24 hours after the event,
      completed the registry's standardized interview, and provided information on
      factors that may have triggered the myocardial infarction. Data on subjects'
      activities during the four days preceding the onset of symptoms were collected
      with the use of patient diaries. RESULTS: An association was found between
      exposure to traffic and the onset of a myocardial infarction within one hour
      afterward (odds ratio, 2.92; 95 percent confidence interval, 2.22 to 3.83;
      P<0.001). The time the subjects spent in cars, on public transportation, or on
      motorcycles or bicycles was consistently linked with an increase in the risk of
      myocardial infarction. Adjusting for the level of exercise on a bicycle or for
      getting up in the morning changed the estimated effect of exposure to traffic
      only slightly (odds ratio for myocardial infarction, 2.73; 95 percent confidence
      interval, 2.06 to 3.61; P<0.001). The subject's use of a car was the most common
      source of exposure to traffic; nevertheless, there was also an association
      between time spent on public transportation and the onset of a myocardial
      infarction one hour later. CONCLUSIONS: Transient exposure to traffic may
      increase the risk of myocardial infarction in susceptible persons.

PMID- 15496622
TI  - Preoperative versus postoperative chemoradiotherapy for rectal cancer.
AB  - BACKGROUND: Postoperative chemoradiotherapy is the recommended standard therapy
      for patients with locally advanced rectal cancer. In recent years, encouraging
      results with preoperative radiotherapy have been reported. We compared
      preoperative chemoradiotherapy with postoperative chemoradiotherapy for locally
      advanced rectal cancer. METHODS: We randomly assigned patients with clinical
      stage T3 or T4 or node-positive disease to receive either preoperative or
      postoperative chemoradiotherapy. The preoperative treatment consisted of 5040 cGy
      delivered in fractions of 180 cGy per day, five days per week, and fluorouracil,
      given in a 120-hour continuous intravenous infusion at a dose of 1000 mg per
      square meter of body-surface area per day during the first and fifth weeks of
      radiotherapy. Surgery was performed six weeks after the completion of
      chemoradiotherapy. One month after surgery, four five-day cycles of fluorouracil
      (500 mg per square meter per day) were given. Chemoradiotherapy was identical in
      the postoperative-treatment group, except for the delivery of a boost of 540 cGy.
      The primary end point was overall survival. RESULTS: Four hundred twenty-one
      patients were randomly assigned to receive preoperative chemoradiotherapy and 402
      patients to receive postoperative chemoradiotherapy. The overall five-year
      survival rates were 76 percent and 74 percent, respectively (P=0.80). The five
      year cumulative incidence of local relapse was 6 percent for patients assigned to
      preoperative chemoradiotherapy and 13 percent in the postoperative-treatment
      group (P=0.006). Grade 3 or 4 acute toxic effects occurred in 27 percent of the
      patients in the preoperative-treatment group, as compared with 40 percent of the
      patients in the postoperative-treatment group (P=0.001); the corresponding rates
      of long-term toxic effects were 14 percent and 24 percent, respectively (P=0.01).
      CONCLUSIONS: Preoperative chemoradiotherapy, as compared with postoperative
      chemoradiotherapy, improved local control and was associated with reduced
      toxicity but did not improve overall survival.

PMID- 15496623
TI  - Dexamethasone for the treatment of tuberculous meningitis in adolescents and
      adults.
AB  - BACKGROUND: Tuberculous meningitis kills or disables more than half of those
      affected with the disease. Previous studies have been too small to determine
      whether adjunctive treatment with corticosteroids can reduce the risk of
      disability or death among adults with tuberculous meningitis, and the effect of
      coinfection with the human immunodeficiency virus (HIV) is unclear. METHODS: We
      performed a randomized, double-blind, placebo-controlled trial in Vietnam in
      patients over 14 years of age who had tuberculous meningitis, with or without HIV
      infection, to determine whether adjunctive treatment with dexamethasone reduced
      the risk of death or severe disability after nine months of follow-up. We
      conducted prespecified subgroup analyses and intention-to-treat analyses.
      RESULTS: A total of 545 patients were randomly assigned to groups that received
      either dexamethasone (274 patients) or placebo (271 patients). Only 10 patients
      (1.8 percent) had been lost to follow-up at nine months of treatment. Treatment
      with dexamethasone was associated with a reduced risk of death (relative risk,
      0.69; 95 percent confidence interval, 0.52 to 0.92; P=0.01). It was not
      associated with a significant reduction in the proportion of severely disabled
      patients (34 of 187 patients [18.2 percent] among survivors in the dexamethasone
      group vs. 22 of 159 patients [13.8 percent] in the placebo group, P=0.27) or in
      the proportion of patients who had either died or were severely disabled after
      nine months (odds ratio, 0.81; 95 percent confidence interval, 0.58 to 1.13;
      P=0.22). The treatment effect was consistent across subgroups that were defined
      by disease-severity grade (stratified relative risk of death, 0.68; 95 percent
      confidence interval, 0.52 to 0.91; P=0.007) and by HIV status (stratified
      relative risk of death, 0.78; 95 percent confidence interval, 0.59 to 1.04;
      P=0.08). Significantly fewer serious adverse events occurred in the dexamethasone
      group than in the placebo group (26 of 274 patients vs. 45 of 271 patients,
      P=0.02). CONCLUSIONS: Adjunctive treatment with dexamethasone improves survival
      in patients over 14 years of age with tuberculous meningitis but probably does
      not prevent severe disability.

PMID- 15496625
TI  - Clinical practice. The thyroid nodule.

PMID- 15496624
TI  - Role of prostanoid DP receptor variants in susceptibility to asthma.
AB  - BACKGROUND: Previous genetic studies have associated the region of the human
      genome (14q22.1) containing the gene for the prostanoid DP receptor (PTGDR) with
      asthma. A study of a mouse model suggests that the receptor is required for the
      expression of the asthma phenotype. Our associations of asthma with functional
      genetic variants of PTGDR link these observations. METHODS: We identified and
      evaluated combinations of genetic variants that influence PTGDR transcription for
      disease association in case-control studies of 518 white patients with asthma and
      175 white controls and 80 black patients with asthma and 45 black controls.
      RESULTS: We identified four novel and two previously reported single-nucleotide
      polymorphisms (SNPs) in PTGDR and its vicinity. These define four common three
      SNP haplotypes, which vary in their ability to support transcription of PTGDR and
      have distinct DNA-binding-protein affinity profiles. Individual PTGDR SNPs were
      significantly associated with asthma in both populations. Specific PTGDR
      haplotypes were significantly associated with a diagnosis of asthma in a large
      case-control study of whites (P=0.002); we confirmed these findings in a second
      population of blacks (P=0.01). Multivariate analysis of the haplotype
      combinations (diplotypes) demonstrated that both whites (odds ratio, 0.55; 95
      percent confidence interval, 0.38 to 0.80; P=0.002) and blacks (odds ratio, 0.32;
      95 percent confidence interval, 0.12 to 0.89; P=0.03) who had at least one copy
      of the haplotype with a low transcriptional efficiency had a lower risk of asthma
      than subjects with no copies of the haplotype. CONCLUSIONS: Our functional and
      genetic findings identify PTGDR as an asthma-susceptibility gene.

PMID- 15496626
TI  - Therapeutic potential of RNA interference.

PMID- 15496627
TI  - Images in clinical medicine. Beau's lines.

PMID- 15496628
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 32-2004. A 68-year-old man with a large retroperitoneal mass.

PMID- 15496629
TI  - Embryonic stem-cell research--the case for federal funding.

PMID- 15496630
TI  - Chemoradiotherapy for rectal cancer--when, why, and how?

PMID- 15496631
TI  - Adjunctive steroids for tuberculous meningitis--more evidence, more questions.

PMID- 15496632
TI  - Making sense of asthma genes.

PMID- 15496633
TI  - Embryonic stem-cell research.

PMID- 15496634
TI  - Combat duty in Iraq and Afghanistan and mental health problems.

PMID- 15496635
TI  - PSA velocity and prostate cancer.

PMID- 15496636
TI  - Prostate cancer with low PSA levels.

PMID- 15496637
TI  - Flavivirus encephalitis.

PMID- 15496638
TI  - Case 22-2004: a 30-year-old woman with a pericardial effusion.

PMID- 15496639
TI  - Effects of fluvoxamine on lansoprazole pharmacokinetics in relation to CYP2C19
      genotypes.
AB  - Lansoprazole is a substrate of CYP2C19 and CYP3A4. The aim of this study was to
      compare the inhibitory effects of fluvoxamine, an inhibitor of CYP2C19, on the
      metabolism of lansoprazole between CYP2C19 genotypes. Eighteen volunteers--of
      whom 6 were homozygous extensive metabolizers (EMs), 6 were heterozygous EMs, and
      6 were poor metabolizers (PMs) for CYP2C19--received three 6-day courses of
      either daily 50 mg fluvoxamine or placebo in a randomized fashion with a single
      oral 60-mg dose of lansoprazole on day 6 in all cases. Plasma concentrations of
      lansoprazole and its metabolites, 5-hydroxylansoprazole and lansoprazole sulfone,
      were monitored up to 24 hours after the dosing. During placebo administration,
      there was a significant difference in the area under the plasma concentration
      time curve from time 0 to infinity (AUC(0-infinity)) of lansoprazole between
      CYP2C19 genotypes. Fluvoxamine treatment increased AUC(0-infinity) of
      lansoprazole by 3.8-fold (P < .01) in homozygous EMs and by 2.5-fold (P < .05) in
      heterozygous EMs, whereas no difference in any pharmacokinetic parameters was
      found in PMs. There was a significant difference in the fluvoxamine-mediated
      percentage increase in the AUC(0-infinity) of lansoprazole between CYP2C19
      genotypes. The present study indicates that there are significant drug
      interactions between lansoprazole and fluvoxamine in EMs. CYP2C19 is
      predominantly involved in lansoprazole metabolism in EMs.

PMID- 15496640
TI  - Lack of a clinically significant effect of zonisamide on phenytoin steady-state
      pharmacokinetics in patients with epilepsy.
AB  - This study was designed to measure the effect of the addition of zonisamide on
      phenytoin pharmacokinetics under steady-state conditions in patients with
      epilepsy. Nineteen patients stabilized under phenytoin monotherapy were included
      in a 3-center, open-label, 1-way drug interaction trial. Zonisamide was gradually
      increased to 400 mg/day, taken twice daily. Three pharmacokinetic profiles were
      performed: on days -7 and -1, to assess pharmacokinetic parameters of oral
      phenytoin administered alone, and on day 35, after 14 days of zonisamide
      treatment, to evaluate the effect of zonisamide on phenytoin pharmacokinetics and
      to characterize zonisamide pharmacokinetics in the presence of phenytoin.
      Fourteen patients completed the study; the coadministration of zonisamide and
      phenytoin was safe and well tolerated. Zonisamide did not significantly affect
      the mean C(min), C(max), AUC(0-12), and CL/F of phenytoin measured before and
      after zonisamide administration. The pharmacokinetic measures of zonisamide in
      the presence of phenytoin were consistent with previous reports of induction of
      zonisamide metabolism by phenytoin.

PMID- 15496641
TI  - Unaltered etanercept pharmacokinetics with concurrent methotrexate in patients
      with rheumatoid arthritis.
AB  - The purpose of this study was to evaluate the potential impact of concurrent
      weekly oral methotrexate administration on the pharmacokinetics of etanercept in
      patients with rheumatoid arthritis (RA) in a phase 3B trial. As part of a double
      blind randomized trial of 682 patients with rheumatoid arthritis who received
      etanercept (25 mg subcutaneously twice weekly), methotrexate (weekly oral dose,
      median weekly dose: 20 mg), or etanercept (25 mg subcutaneously twice weekly)
      plus methotrexate (weekly oral dose, median weekly dose: 20 mg), serum etanercept
      concentrations were measured in a subset of patients. Serum samples for 98
      randomly selected patients (48 receiving etanercept-alone treatment, 50 receiving
      etanercept plus methotrexate combination treatment) were analyzed to assess the
      pharmacokinetics of etanercept. A single blood sample was drawn from each patient
      at baseline and at the week 24 visit. Given the variable sampling time for
      patients in both groups, a population pharmacokinetic analysis using NONMEM was
      conducted for etanercept. A final covariate population pharmacokinetic model was
      constructed based on previously obtained etanercept data from both healthy
      subjects (n = 53) and patients with RA (n = 212) in 10 prior clinical trials. The
      predictive performance of the final model was assessed by both bootstrap and data
      splitting validation approaches. The final model was then used to estimate
      Bayesian pharmacokinetic parameters for the patients in both treatments in the
      current trial. The potential effect of the concurrent administration of
      methotrexate on the pharmacokinetics of etanercept was examined by comparing the
      clearance values between 2 treatments using statistical criteria. A population 2
      compartment model with first-order elimination from the central compartment and
      with either zero-order (intravenous administration) or first-order (subcutaneous
      administration) input was selected based on the data from the prior 10 etanercept
      clinical studies. The following pharmacokinetic parameters (typical value +/-
      standard error) were estimated: clearance (CL: 0.072 +/- 0.005 L/h), volume of
      distribution in the central compartment (V(c): 5.97 +/- 0.45 L), volume of
      distribution in the peripheral compartment (V(p): 2.05 +/- 0.32 L),
      intercompartment clearance (Q: 0.0645 +/- 0.0093 L/h), first-order absorption
      rate constant (k(a): 0.0282 +/- 0.0039 1/h), and absolute bioavailability for
      subcutaneous administration (F: 0.626 +/- 0.056). Interindividual variability of
      the pharmacokinetic parameters was quantified for CL (25.1%), V(c) (41.7%), k(a)
      (53.1%), and F (24.2%). Residual variability consisted of combined additive (11.4
      ng/mL) and proportional error (49.9%). Both age (< 17 years) and body weight (<
      60 kg) were found to be important covariates on CL. The results of both
      validation tests indicated the adequate predictive performance of the population
      model. Based on the bioequivalence criteria, the Bayesian-estimated clearance for
      patients receiving etanercept alone (mean: 0.070 L/h) was comparable to that for
      patients receiving a combination of etanercept and methotrexate (mean = 0.066
      L/h). The pharmacokinetics of etanercept were not altered by the concurrent
      administration of methotrexate in patients with rheumatoid arthritis. Thus, no
      etanercept dose adjustment is needed for patients taking concurrent methotrexate.

PMID- 15496642
TI  - Absence of a clinically relevant interaction between etanercept and digoxin.
AB  - Etanercept, a soluble recombinant human tumor necrosis factor receptor (TNFr), is
      effective and well tolerated in the treatment of rheumatoid arthritis, juvenile
      rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and psoriasis.
      The primary objective of this study was to investigate the potential
      pharmacokinetic and pharmacodynamic interaction between digoxin and etanercept at
      steady state. In a crossover, open-label, nonrandomized, 3-period study, 12
      healthy male subjects received loading oral doses of digoxin 0.5 mg every 12
      hours on day 1 and 0.25 mg every 12 hours on day 2, followed by a daily
      maintenance dose of 0.25 mg for a total of 27 days. Etanercept was administered
      as a twice-weekly 25-mg subcutaneous dose beginning on day 9 and continuing up to
      day 37 for a total of 9 doses. All ratios of maximum plasma concentration
      (C(max)) and area under the plasma concentration versus time curve (AUC) for
      pharmacokinetics of digoxin fell within the confidence interval of 0.8 to 1.25.
      Although not considered clinically relevant, the mean C(max) and AUC of
      etanercept were 4.2% and 12.5% lower, respectively, when etanercept was given
      with digoxin than when administered alone. There were no clinically relevant
      changes in the electrocardiogram (ECG) parameters, and adverse events did not
      increase when both drugs were combined. In conclusion, there is no clinically
      relevant interaction between etanercept and digoxin, and both drugs can be safely
      coadministered without the need for a dosage adjustment.

PMID- 15496643
TI  - Pharmacokinetics/pharmacodynamics of desloratadine and fluoxetine in healthy
      volunteers.
AB  - The authors assessed the potential for a pharmacokinetic/pharmacodynamic
      interaction between desloratadine and fluoxetine. This randomized, placebo
      controlled, open-label study was conducted in 54 healthy volunteers. Subjects
      received 1 of 3 treatments: desloratadine 5 mg plus fluoxetine 20 mg,
      desloratadine 5 mg plus placebo, or fluoxetine 20 mg plus placebo. Serial
      electrocardiograms (ECGs) were performed at baseline and day 35. Treatment
      effects on C(max) and AUC were assessed. During coadministration of desloratadine
      with fluoxetine, the ratio of the mean log-transformed C(max) and AUC values for
      desloratadine following concomitant fluoxetine therapy revealed a small increase
      in C(max) values of 15% (90% confidence interval [CI], 95%-139%) but no increase
      for AUC values (90% CI, 82%-123%). Corresponding values for 3-OH desloratadine
      demonstrated small increases in mean log-transformed C(max) and AUC ratios: 17%
      (90% CI, 100%-136%) and 13% (90% CI, 96%-132%), respectively. Statistical
      evaluation of the ratio of the mean C(max) and AUC values for fluoxetine
      following concomitant desloratadine therapy revealed small decreases of 9% (90%
      CI, 72%-115%) and 11% (90% CI, 69%-113%), respectively. Corresponding values for
      norfluoxetine demonstrated modest increases in mean log-transformed C(max) and
      AUC ratios: 22% (90% CI, 100%-139%) and 18% (90% CI, 101%-136%), respectively.
      Coadministration of desloratadine with a potent inhibitor of CYP2D6 did not
      result in clinically relevant changes in its pharmacokinetic parameters.
      Desloratadine administration was not associated with clinically important changes
      in the pharmacokinetics of fluoxetine, a drug metabolized by CYP2D6. The most
      common adverse event in all groups was headache (65%). Desloratadine plus
      fluoxetine caused no significant changes in ECGs or ventricular rate.

PMID- 15496644
TI  - Important role of the dihydrouracil/uracil ratio in marked interpatient
      variations of fluoropyrimidine pharmacokinetics and pharmacodynamics.
AB  - Dihydropyrimidine dehydrogenase (DPD) deficiency in patients causes severe
      toxicities in 5-fluorouracil/floxuridine (5-FU/FUDR) treatments. To determine the
      plasma dihydrouracil/uracil ratio (DUUR) as a potential index for setting 5
      FU/FUDR doses, the authors conducted a prospective study on the relationships of
      the DUUR with 5-FU/FUDR pharmacokinetic and pharmacodynamic parameters. Forty
      gestational trophoblastic tumor (GTT) patients were treated with 30 mg/kg of 5-FU
      or prodrug FUDR during a 10-day cycle. The pretreatment DUURs of the patients
      were determined prior to the treatments, and plasma 5-FU and FUDR concentrations
      on day 1 of the test cycle were measured to calculate the corresponding
      pharmacokinetic parameters. The absolute neutrophil count (ANC) and human
      chorionic gonadotrophins (HCG/beta-HCG) were recorded as the efficacy indexes.
      The correlation of the DUUR with pharmacokinetic parameters and efficacy indexes
      was analyzed to look for a relationship between individual doses (in milligrams)
      and the varied DUUR. Pretreatment DUUR was significantly correlated with the
      corresponding plasma AUC (r > 0.80, P < .01), the plasma drug clearance (r >
      0.78, P < .01), the ANC (r > 0.76, P < 0.01), and the decrease of HCG/beta-HCG
      levels (r > 0.5, P < 0.01). In addition, the charts for setting 5-FU/FUDR doses
      were designed for further validation in clinical trials. These findings indicate
      the important roles of the DUUR in remarkable interpatient variations of
      fluoropyrimidine pharmacokinetics and pharmacodynamics and propose a better index
      for setting individual 5-FU/FUDR doses based on interpatient variations in DPD
      levels.

PMID- 15496645
TI  - Induction of CYP3A4 by efavirenz in primary human hepatocytes: comparison with
      rifampin and phenobarbital.
AB  - The antiretroviral agent efavirenz enhances the systemic clearance of
      coadministered drugs that are cytochrome P450 (CYP) 3A4 substrates. The mechanism
      of the apparent increase in CYP3A4 activity by efavirenz and the magnitude of
      change relative to other known inducers are not known. The authors tested the
      hypothesis that increased enzymatic activity by efavirenz entails CYP3A4
      induction and activation of the human pregnane X receptor (hPXR), a key
      transcriptional regulator of CYP3A4. Employing primary cultures of human
      hepatocytes, they compared the CYP3A4 inductive effects of efavirenz (1-10
      microM) to rifampin (10 microM) and phenobarbital (2 mM). A cell-based reporter
      assay was employed to assess hPXR activation. The authors observed that efavirenz
      caused a concentration-dependent CYP3A4 induction and hPXR activation. Based on
      the CYP3A4 activity assay, the average magnitude of induction by efavirenz (5-10
      microM) was approximately 3- to 4-fold. In comparison, phenobarbital (2 mM) and
      rifampin (10 microM) caused a 5- and 6-fold induction, respectively.

PMID- 15496646
TI  - Pharmacokinetics of articaine hydrochloride in tumescent local anesthesia for
      liposuction.
AB  - The aim of the investigation was to assess the pharmacokinetic characteristics
      and safety of articaine HCl used in tumescent local anesthesia for liposuction.
      Maximum plasma concentrations of articaine HCl were observed from 136 to 264
      ng/mL, on average, from 1.2 to 4.3 hours after the start of infiltration,
      depending on the area of liposuction. The average extent of absorption ranged
      from 827 to 2203 ng*h/mL. Average maximum plasma concentrations of articainic
      acid ranged from 1719 to 7292 ng/mL. The high articainic acid concentrations at 1
      hour after the start of infiltration indicate that articaine HCl was hydrolyzed
      rapidly by esterases in tissue and plasma. Although up to 38.2 mg/kg body weight
      articaine HCl was applied, no cardiac side effects or symptoms of central nervous
      intoxication occurred. Articaine HCl provided a safe and sufficient analgesia for
      tumescent liposuction.

PMID- 15496647
TI  - Oxcarbazepine pharmacokinetics and tolerability in children with inadequately
      controlled epilepsy.
AB  - This two-part, open-label study evaluated the pharmacokinetics, safety, and
      tolerability of oxcarbazepine as combination therapy in 112 children 2 to 12
      years old with inadequately controlled epilepsy. Part I was a pharmacokinetic
      study in children stratified by age (2-5 years and 6-12 years) and randomized to
      receive a single oxcarbazepine dose of 5 mg/kg or 15 mg/kg. Mean specific AUC and
      t(1/2) values of the active metabolite (MHD) were approximately 30% lower in
      younger children compared with older children, regardless of dose. Part II was a
      4-month safety, tolerability, and pharmacokinetic study in which children
      received oxcarbazepine doses of 11 to 68 mg/kg/day. The mean specific
      oxcarbazepine daily dose was 38% higher in younger children compared with older
      children. Similarly, mean trough plasma MHD concentrations were 34% lower in
      younger children. Six (5%) children discontinued due to adverse events.
      Oxcarbazepine was safe and well tolerated. Younger children require higher
      oxcarbazepine doses because of rapid clearance.

PMID- 15496648
TI  - Pharmacokinetic and pharmacodynamic analysis of amprenavir-containing combination
      therapy in HIV-1-infected children.
AB  - Several factors influence the antiviral response to antiretroviral therapy. In
      this pharmacokinetic and pharmacodynamic analysis, the relationship of drug
      exposure, demographics, and cotherapy measures to antiviral response in a cohort
      of largely treatment-experienced children treated with amprenavir and nucleoside
      reverse transcriptase inhibitors was examined. Multiple pharmacodynamic and
      demographic factors were examined, but only the minimum plasma concentration
      (C(min))/protein-binding-adjusted 50% inhibitory drug concentration (IC(50))
      ratio and whether individuals received 2 versus fewer than 2 nucleosides to which
      their viral isolates were susceptible were associated with the magnitude of the
      time-weighted average change in HIV-1 RNA log(10) copies/mL from baseline
      (AAUCMB). In multivariate logistic regression analysis, only the C(min)/IC(50)
      ratio was independently associated with having a >or=1 log(10) AAUCMB decline.
      The probability in the study population of having a >or=1log(10) AAUCMB was 50%
      and 85% at C(min)/IC(50) ratios of approximately 1 and 4, respectively. Of the
      multiple factors examined, only the C(min)/IC(50) ratio was a significant
      predictor of antiviral response in the first 8 weeks on amprenavir-containing
      combination antiretroviral therapy.

PMID- 15496649
TI  - Population pharmacokinetics of clofarabine, a second-generation nucleoside
      analog, in pediatric patients with acute leukemia.
AB  - The population pharmacokinetics of plasma clofarabine and intracellular
      clofarabine triphosphate were characterized in pediatric patients with acute
      leukemias. Traditional model-building techniques with NONMEM were used.
      Covariates were entered into the base model using a forward selection
      significance level of .05 and a backwards deletion criterion of .005. Model
      performance, stability, and influence analysis were assessed using the
      nonparametric bootstrap and n-1 jackknife. Simulations were used to understand
      the relationship between important covariates and exposure. A 2-compartment model
      with weight (scaled to a 40-kg reference patient) modeled as a power function on
      all pharmacokinetic parameters (0.75 on clearance-related terms and 1.0 on volume
      related terms) was fit to plasma clofarabine concentrations (n = 32). White blood
      cell (WBC) count, modeled as a power function (scaled to a WBC count of 10 x
      10(3)/microL), was a significant predictor of central volume with power term
      0.128 +/- 0.0314. A reference patient had a systemic clearance of 32.8 L/h (27%
      between-subject variability [BSV]), a central volume of 115 L (56% BSV), an
      intercompartmental clearance of 20.5 L/h (27% BSV), and a peripheral volume of
      94.5 L (39% BSV). Intracellular clofarabine triphosphate concentrations were
      modeled using a random intercept model without any covariates. The average
      predicted concentration was 11.6 +/- 2.62 microM (80% BSV), and although
      clofarabine triphosphate half-life could not be definitively estimated, its value
      was taken to be longer than 24 hours. The results confirm that clofarabine should
      continue being dosed on a per-squaremeter or per-body-weight basis.

PMID- 15496650
TI  - Effects of Corydalis yanhusuo and Angelicae dahuricae on cold pressor-induced
      pain in humans: a controlled trial.
AB  - Pain is considered the most common complaint worldwide for which patients seek
      treatment. Conventional analgesic agents play an important role in modern pain
      therapy, but they cause several adverse effects. Therefore, newer and better
      analgesics continue to be investigated. In this controlled clinical trial, the
      authors evaluated the analgesic effects of 2 herbal medicines, Corydalis yanhusuo
      and Angelicae dahuricae. They used the cold-pressor test-a simple, reliable, and
      widely used model in humans-for induction of tonic pain. They demonstrated that
      after a single, oral administration of the extracts of C. yanhusuo and A.
      dahuricae, the pain intensity and pain bothersomeness scores significantly
      decreased (both P < .01). Dose-related analgesic effect was also observed.
      Results from this study suggest that C. yanhusuo and A. dahuricae may have a
      potential clinical value for treating mild to moderate pain.

PMID- 15496651
TI  - Glycoprotein IIb/IIIa receptor antagonists and risk of bleeding: a single-center
      experience in 1020 patients.
AB  - The safety of glycoprotein (GP) IIb/IIIa inhibitors has been well documented in
      clinical trials. Although these trials have included a broad patient population,
      the strict enrollment criteria may have resulted in exclusion of patients at a
      higher risk of bleeding complications. The authors conducted a retrospective
      chart review of 1020 consecutive patients who received GP IIb/IIIa inhibitors and
      underwent percutaneous coronary intervention in a large community hospital. They
      used Thrombolysis in Myocardial Infarction (TIMI) criteria to define major or
      minor bleeding complications. Bleeding complications developed in 214 (21%)
      patients, with major bleeding in 89 (9%). Univariate predictors of bleeding were
      older age, lower body weight, elevated serum creatinine, higher activated partial
      thromboplastin time (aPTT) level, history of diabetes mellitus (DM), peripheral
      vascular disease (PVD), congestive heart failure (CHF), and emergency procedure
      for acute myocardial infarction (AMI). Multivariate predictors of major bleeding
      were PVD (20% in bleeding group vs 11% in nonbleeders, odds ratio [OR] = 1.8, 95%
      confidence interval [CI] = 1.2-2.6, P < .004), age (68 +/- 2 years, 95% CI = 66
      70 in bleeding group vs 63 +/- 13 years, 95% CI = 61.2-63 in nonbleeders, P <
      .001), and higher aPTT level (66 +/- 27 seconds, 95% CI = 63-70 in bleeding group
      vs 53 +/- 28 seconds, 95% CI = 51-56 in nonbleeders, P < .001). The risk of
      bleeding in the large community hospital setting may be higher than in randomized
      clinical trials. This increased risk is associated with higher hospitalization
      costs. Recognition of predictors of bleeding should further enhance the safety of
      these antiplatelet agents.

PMID- 15496653
TI  - The beat goes on: spontaneous firing in mammalian neuronal microcircuits.

PMID- 15496654
TI  - Molecules and mechanisms of mechanotransduction.

PMID- 15496655
TI  - Novel approaches to monitor and manipulate single neurons in vivo.

PMID- 15496656
TI  - Autism and abnormal development of brain connectivity.

PMID- 15496657
TI  - Divide and die: cell cycle events as triggers of nerve cell death.

PMID- 15496658
TI  - Neuronal oscillations in the basal ganglia and movement disorders: evidence from
      whole animal and human recordings.

PMID- 15496659
TI  - Cell adhesion molecules in synapse formation.
AB  - Neuronal transmission relies on signals transmitted through a vast array of
      excitatory and inhibitory neuronal synaptic connections. How do axons communicate
      with dendrites to build synapses, and what molecules regulate this interaction?
      There is a wealth of evidence suggesting that cell adhesion molecules (CAMs)
      provide much of the information required for synapse formation. This review
      highlights the molecular mechanisms used by CAMs to regulate presynaptic and
      postsynaptic differentiation.

PMID- 15496660
TI  - Mechanisms and roles of axon-Schwann cell interactions.

PMID- 15496661
TI  - Prenatal nicotine exposure alters central cardiorespiratory responses to hypoxia
      in rats: implications for sudden infant death syndrome.
AB  - Maternal cigarette smoking and prenatal nicotine exposure are the highest risk
      factors for sudden infant death syndrome (SIDS). During hypoxia, respiratory
      frequency and heart rate transiently increase and subsequently decrease. These
      biphasic cardiorespiratory responses normally serve to prolong survival during
      hypoxia by reducing the metabolic demands of cardiac and respiratory muscles.
      However, exaggerated responses to hypoxia may be life threatening and have been
      implicated in SIDS. Heart rate is primarily determined by the activity of
      brainstem preganglionic cardioinhibitory vagal neurons (CVNs) in the nucleus
      ambiguus. We developed an in vitro rat brainstem slice preparation that maintains
      rhythmic inspiratory-related activity and contains fluorescently labeled CVNs.
      Synaptic inputs to CVNs were examined using patch-clamp electrophysiological
      techniques. Hypoxia evoked a biphasic change in the frequency of both GABAergic
      and glycinergic IPSCs in CVNs, comprised of an initial increase followed by a
      decrease in IPSC frequency. Prenatal exposure to nicotine changed the GABAergic
      response to hypoxia from a biphasic response to a precipitous decrease in
      spontaneous GABAergic IPSC frequency. This study establishes a likely
      neurochemical mechanism for the heart rate response to hypoxia and a link between
      prenatal nicotine exposure and an exaggerated bradycardia during hypoxia that may
      contribute to SIDS.

PMID- 15496662
TI  - Characterization of fear memory reconsolidation.
AB  - Reactivation of consolidated memories returns them to a protein synthesis
      dependent state. One interpretation of these findings is that the memory
      reconsolidates after use. Two alternative interpretations are that protein
      synthesis inhibition facilitates extinction and that postreactivation protein
      synthesis inhibition leads to an inability to retrieve the consolidated memory.
      First, using two different approaches, we report that reconsolidation cannot be
      reduced down to facilitated extinction. We show that the reconsolidation deficit
      does not show renewal after a contextual shift, whereas an extinguished auditory
      fear memory does under the same conditions and the deficit occurs regardless of
      whether the memory is reactivated with an extinction [conditioned stimulus (CS)
      alone] or a reinforced trial (CS-unconditioned stimulus). To address the issue of
      whether postreactivation anisomycin leads to an inability to retrieve the
      consolidated memory, we used two traditional assays for retrieval deficits.
      First, we demonstrate that the amnesia induced by blockade of reconsolidation
      does not show any spontaneous recovery. Second, we show that application of
      reminder shock does not result in the reinstatement of the memory. These findings
      support the idea that reactivation of consolidated memories initiates a second
      time-dependent memory formation process.

PMID- 15496663
TI  - The subfornical organ is the primary locus of sodium-level sensing by Na(x)
      sodium channels for the control of salt-intake behavior.
AB  - Dehydration causes an increase in the sodium (Na) concentration and osmolarity of
      body fluid. For Na homeostasis of the body, controls of Na and water intake and
      excretion are of prime importance. However, the system for sensing the Na level
      within the brain that is responsible for the control of Na- and water-intake
      behavior remains to be elucidated. We reported previously that the Na(x) channel
      is preferentially expressed in the circumventricular organs (CVOs) in the brain
      and that Na(x) knock-out mice ingest saline in excess under dehydrated
      conditions. Subsequently, we demonstrated that Na(x) is a Na-level-sensitive Na
      channel. Here we show that the subfornical organ (SFO) is the principal site for
      the control of salt-intake behavior, where the Na(x) channel is the Na-level
      sensor. Infusion of a hypertonic Na solution into the cerebral ventricle induced
      extensive water intake and aversion to saline in wild-type animals but not in the
      knock-out mice. Importantly, the aversion to salt was not induced by the infusion
      of a hyperosmotic mannitol solution with physiological Na concentration in either
      genotype of mice. When Na(x) cDNA was introduced into the brain of the knock-out
      mice with an adenoviral expression vector, only animals that received a
      transduction of the Na(x) gene into the SFO among the CVOs recovered salt
      avoiding behavior under dehydrated conditions. These results clearly show that
      the SFO is the center of the control of salt-intake behavior in the brain, where
      the Na-level-sensitive Na(x) channel is involved in sensing the physiological
      increase in the Na level of body fluids.

PMID- 15496664
TI  - Astrocyte-associated fibronectin is critical for axonal regeneration in adult
      white matter.
AB  - Although it has been suggested that astroglia guide pioneering axons during
      development, the cellular and molecular substrates that direct axon regeneration
      in adult white matter have not been elucidated. We show that although adult
      cortical neurons were only able to elaborate very short, highly branched,
      dendritic-like processes when seeded onto organotypic slice cultures of postnatal
      day 35 (P35) rat brain containing the corpus callosum, adult dorsal root ganglion
      (DRG) neurons were able to regenerate lengthy axons within the reactive glial
      environment of this degenerating white matter tract. The callosum in both P35
      slices and adult rat brain was rich in fibronectin, but not laminin. Furthermore,
      the fibronectin was intimately associated with the intratract astrocytes.
      Blockade of fibronectin function in situ with an anti-fibronectin antibody
      dramatically decreased outgrowth of DRG neurites, suggesting that fibronectin
      plays an important role in axon regeneration in mature white matter. The critical
      interaction between regrowing axons and astroglial-associated fibronectin in
      white matter may be an additional factor to consider when trying to understand
      regeneration failure and devising strategies to promote regeneration.

PMID- 15496665
TI  - Dynamic sound localization during rapid eye-head gaze shifts.
AB  - Human sound localization relies on implicit head-centered acoustic cues. However,
      to create a stable and accurate representation of sounds despite intervening head
      movements, the acoustic input should be continuously combined with feedback
      signals about changes in head orientation. Alternatively, the auditory target
      coordinates could be updated in advance by using either the preprogrammed gaze
      motor command or the sensory target coordinates to which the intervening gaze
      shift is made ("predictive remapping"). So far, previous experiments cannot
      dissociate these alternatives. Here, we study whether the auditory system
      compensates for ongoing saccadic eye and head movements in two dimensions that
      occur during target presentation. In this case, the system has to deal with
      dynamic changes of the acoustic cues as well as with rapid changes in relative
      eye and head orientation that cannot be preprogrammed by the audiomotor system.
      We performed visual-auditory double-step experiments in two dimensions in which a
      brief sound burst was presented while subjects made a saccadic eye-head gaze
      shift toward a previously flashed visual target. Our results show that
      localization responses under these dynamic conditions remain accurate. Multiple
      linear regression analysis revealed that the intervening eye and head movements
      are fully accounted for. Moreover, elevation response components were more
      accurate for longer-duration sounds (50 msec) than for extremely brief sounds (3
      msec), for all localization conditions. Taken together, these results cannot be
      explained by a predictive remapping scheme. Rather, we conclude that the human
      auditory system adequately processes dynamically varying acoustic cues that
      result from self-initiated rapid head movements to construct a stable
      representation of the target in world coordinates. This signal is subsequently
      used to program accurate eye and head localization responses.

PMID- 15496666
TI  - Spontaneous withdrawal from the triazolobenzodiazepine alprazolam increases
      cortical corticotropin-releasing factor mRNA expression.
AB  - Corticotropin-releasing factor (CRF) is the major physiologic regulator of the
      hypothalamic-pituitary-adrenal (HPA) axis and plays a key role in coordinating
      the mammalian stress response. Substantial data implicates hyperactivity of CRF
      neuronal systems in the pathophysiology of depression and anxiety disorders.
      Enhanced CRF expression, release, and function have also been demonstrated during
      acute withdrawal from several drugs of abuse. Previous studies revealed that
      chronic administration of the anxiolytic alprazolam reduced indices of CRF and
      CRF1 receptor function. Conversely, measures of urocortin I and CRF2 receptor
      function were increased. To further scrutinize these findings, we sought to
      determine whether CRF neuronal systems are activated during spontaneous
      withdrawal from the triazolobenzodiazepine alprazolam in dependent rats and to
      characterize the time course, extent, and regional specificity of the patterns of
      activation. After 14 d of alprazolam administration (90 mg x kg(-1) x d(-1)),
      spontaneous withdrawal produced activation of the HPA axis, as well as
      suppression of food intake and weight loss that peaked 24-48 hr after withdrawal.
      Remarkably, CRF mRNA expression in the cerebral cortex was markedly (>300%)
      increased over the same time period. Other indices of CRF-CRF1 and urocortin I
      CRF2A function, altered by chronic alprazolam treatment as previously described,
      returned to pretreatment levels over 96 hr. The physiologic significance of this
      dramatic induction of cortical CRF mRNA expression, as well as whether this
      occurs during withdrawal from other drugs of abuse is yet to be determined. The
      marked increase in CRFergic neurotransmission is hypothesized to play a major
      role in benzodiazepine withdrawal.

PMID- 15496667
TI  - The effects on place cells of local scopolamine dialysis are mimicked by a
      mixture of two specific muscarinic antagonists.
AB  - Using a dialysis probe near CA1 hippocampal recording electrodes, we infused
      nonspecific (scopolamine) and specific (methoctramine, pirenzepine) antagonists
      of muscarinic cholinergic transmission to determine their effects on the
      positional firing properties of place cells. Both low (0.5 mM) and high (2.0 or
      3.0 mM) scopolamine significantly decreased in-field firing rate, increased the
      ratio of out-of-field to in-field rate, and reduced the smoothness of rate maps,
      while tending to increase out-of-field rate. Thus, local nonspecific muscarinic
      blockade mimicked the effects seen with intracerebroventricular application,
      suggesting that blockade of receptors local to the recorded cells plays an
      essential role. Unexpectedly, dialysis of scopolamine reduced locomotor activity,
      again duplicating the effects of intracerebroventricular administration. Most
      effects of methoctramine (1.0 mM), which blocks presynaptic m2 and m4 receptors,
      were initially strong but then diminished over hours. Methoctramine produced a
      significant increase only in out/in ratio and out-of-field rate, whereas it
      tended to increase in-field rate and monotonically decrease smoothness.
      Pirenzepine (3.0 mM), which blocks postsynaptic m1 receptors, produced a
      significant increase only in out/in ratio, whereas it tended to increase out-of
      field rate and decrease in-field rate; all these effects were monotonic with
      respect to time. A mixture of methoctramine plus pirenzepine recapitulated the
      place-cell effects of scopolamine, although neither the mixture nor its separate
      components affected behavior. We conclude that the effects of scopolamine on
      place cells likely result from a combination of blockade of postsynaptic m1
      receptors, leading to reduced excitability, with blockade of presynaptic m2 and
      m4 receptors, leading to increased out-of-field firing.

PMID- 15496668
TI  - Persistent accumulation of calcium/calmodulin-dependent protein kinase II in
      dendritic spines after induction of NMDA receptor-dependent chemical long-term
      potentiation.
AB  - Calcium/calmodulin-dependent protein kinase II (CaMKII) is a leading candidate
      for a synaptic memory molecule because it is persistently activated after long
      term potentiation (LTP) induction and because mutations that block this
      persistent activity prevent LTP and learning. Previous work showed that synaptic
      stimulation causes a rapidly reversible translocation of CaMKII to the synaptic
      region. We have now measured green fluorescent protein (GFP)-CaMKIIalpha
      translocation into synaptic spines during NMDA receptor-dependent chemical LTP
      (cLTP) and find that under these conditions, translocation is persistent. Using
      red fluorescent protein as a cell morphology marker, we found that there are two
      components of the persistent accumulation. cLTP produces a persistent increase in
      spine volume, and some of the increase in GFP-CaMKIIalpha is secondary to this
      volume change. In addition, cLTP results in a dramatic increase in the bound
      fraction of GFP-CaMKIIalpha in spines. To further study the bound pool,
      immunogold electron microscopy was used to measure CaMKIIalpha in the
      postsynaptic density (PSD), an important regulator of synaptic function. cLTP
      produced a persistent increase in the PSD-associated pool of CaMKIIalpha. These
      results are consistent with the hypothesis that CaMKIIalpha accumulation at
      synapses is a memory trace of past synaptic activity.

PMID- 15496669
TI  - Cranial afferent glutamate heterosynaptically modulates GABA release onto second
      order neurons via distinctly segregated metabotropic glutamate receptors.
AB  - The balance between excitation and inhibition dictates central integration.
      Glutamatergic and GABAergic neurotransmission dominate this process. Cranial
      primary afferents enter the brainstem to release glutamate (Glu) onto second
      order neurons within the caudal nucleus tractus solitarius (NTS) to initiate
      autonomic reflexes. The simplest pathways for these reflexes contain as few as
      two central neurons, but display robust frequency-dependent behavior. Within NTS,
      multiple metabotropic Glu receptors (mGluRs) are present, but their roles are
      poorly understood. Using synaptically discriminated second-order NTS neurons in
      brainstem slices and mechanically dissociated NTS neurons with intact boutons, we
      show that Glu differentially controls GABA release via distinct presynaptic
      mGluRs. In second-order NTS neurons recorded in slices, activation of primary
      afferents at frequencies as low as 10 shocks per second released sufficient Glu
      to alter rates of spontaneous IPSCs (sIPSCs). In both approaches, group I mGluRs
      increased GABA release in some neurons, but, on different neurons, group II and
      group III mGluRs decreased the sIPSC rate. mGluR actions were remarkably rapid,
      with onset and reversal beginning within 100 msec. In all cases, mGluR actions
      were exclusively presynaptic, and mGluRs did not alter postsynaptic properties in
      second-order neurons in either slices or isolated neurons. Tests with capsaicin
      and alphabeta-methylene ATP suggest that myelinated and unmyelinated afferent
      pathways engage both mGluR-GABA mechanisms. Afferent Glu spillover provides
      heterosynaptic cross talk with GABAergic inhibition in NTS. This process may
      critically shape the dynamic character and use dependence for cranial afferent
      transmission at the first stage of autonomic reflexes.

PMID- 15496670
TI  - Action potential backpropagation and multiglomerular signaling in the rat
      vomeronasal system.
AB  - In the accessory olfactory bulb (AOB), sensory neurons expressing a given
      vomeronasal receptor (VR) gene send divergent projections to many glomeruli, and
      second-order neurons (mitral cells) link to multiple glomeruli via branched
      primary dendrites. We used calcium imaging and paired somadendritic patch-clamp
      recording to track backpropagated action potentials (APs) in rat AOB primary
      dendrites. In cells loaded with 150 microm Calcium Orange, somatic spikes
      elicited fluorescence transients over the entire primary dendritic tree, and the
      relative fluorescence increment DeltaF/F(0) increased along all branches from
      soma to glomeruli. Backpropagation was reliant on Na+ channels: in 1 microm TTX,
      somatic AP commands evoked dendritic Ca2+ transients that declined steeply with
      distance. In paired soma- dendritic whole-cell recordings, backpropagated APs
      were unattenuated up to approximately 200 microm from the soma, whereas
      subthreshold voltage transients decayed markedly. Computational modeling
      indicated that the large distal Ca2+ transients are consistent with active, not
      passive, backpropagation. Genetic tracing in the AOB has suggested homotypic
      connectivity with individual mitral cell dendritic arbors projecting only to
      glomeruli targeted by sensory neurons expressing the same VR gene. Non
      decremental, non-dichotomous backpropagation in AOB primary dendrites ensures
      fast, reliable communication between mitral cells and their homotypic glomeruli,
      binding them into functional modules in accordance with their VR-coded inputs.

PMID- 15496671
TI  - Localizing P300 generators in visual target and distractor processing: a combined
      event-related potential and functional magnetic resonance imaging study.
AB  - Constraints from functional magnetic resonance imaging (fMRI) were used to
      identify the sources of the visual P300 event-related potential (ERP). Healthy
      subjects performed a visual three-stimulus oddball paradigm with a difficult
      discrimination task while fMRI and high-density ERP data were acquired in
      separate sessions. This paradigm allowed us to differentiate the P3b component of
      the P300, which has been implicated in the detection of rare events in general
      (target and distractor), from the P3a component, which is mainly evoked by
      distractor events. The fMRI-constrained source model explained >99% of the
      variance of the scalp ERP for both components. The P3b was mainly produced by
      parietal and inferior temporal areas, whereas frontal areas and the insula
      contributed mainly to the P3a. This source model reveals that both higher visual
      and supramodal association areas contribute to the visual P3b and that the P3a
      has a strong frontal contribution, which is compatible with its more anterior
      distribution on the scalp. The results point to the involvement of distinct
      attentional subsystems in target and distractor processing.

PMID- 15496672
TI  - Biochemical, ultrastructural, and reversibility studies on huntingtin filaments
      isolated from mouse and human brain.
AB  - Huntington's disease (HD) and eight additional inherited neurological disorders
      are caused by CAG triplet-repeat expansions leading to expanded polyglutamine
      sequences in their respective proteins. These triplet-CAG repeat disorders have
      in common the formation of aberrant intraneuronal proteinaceous inclusions
      containing the expanded polyglutamine sequences. These aggregates have been
      postulated to contribute to pathogenesis caused by conformational toxicity,
      sequestration of other polyglutamine-containing proteins, or by interfering with
      certain enzymatic activities. Testing these hypotheses has been hampered by the
      difficulty to isolate these aggregates from brain. Here we report that
      polyglutamine aggregates can be isolated from the brain of the Tet/HD94
      conditional mouse model of HD, by following a method based on high salt buffer
      homogenization, nonionic detergent extraction, and gradient fractionation. We
      then verified that the method can be successfully applied to postmortem HD
      brains. Immunoelectron microscopy, both in human and mouse samples, revealed that
      the stable component of the inclusions are mutant huntingtin-containing and
      ubiquitin-containing fibrils. Atomic-force microscopy revealed that these fibrils
      have a "beads on a string" morphology. Thus, they resemble the in vitro assembled
      filaments made of recombinant mutant-huntingtin, as well as the Abeta and alpha
      synuclein amyloid protofibrils. Finally, by shutting down transgene expression in
      the Tet/HD94 conditional mouse model of HD, we were able to demonstrate that
      these filaments, although stable in vitro, are susceptible to revert in vivo,
      thus demonstrating that the previously reported reversal of ubiquitin
      immunoreactive inclusions does not simply reflect disassembling of the inclusions
      into their constituent fibrils and suggesting that any associated conformational
      or protein-sequestration toxicity is also likely to revert.

PMID- 15496673
TI  - Polysialylated neural cell adhesion molecule promotes remodeling and formation of
      hippocampal synapses.
AB  - Expression of the neural cell adhesion molecule (NCAM) has been shown to promote
      long-term potentiation (LTP) and stabilization of synapses during early
      synaptogenesis. Here, we searched for the mechanisms of synaptogenic activity of
      NCAM, focusing on the role of polysialic acid (PSA), an unusual carbohydrate
      preferentially associated with NCAM. We show that enzymatic removal of PSA with
      endoneuraminidase-N (endo-N) abolished preferential formation of synapses on NCAM
      expressing cells in heterogenotypic cocultures of wild-type and NCAM-deficient
      hippocampal neurons. Transfection of NCAM-deficient neurons with either of three
      major NCAM isoforms (different in intracellular domains but identical in
      extracellular domains and carrying PSA) stimulated preferential synapse formation
      on NCAM isoform-expressing neurons. Enzymatic removal of heparan sulfates from
      cultured neurons and a mutation in the heparin-binding domain of NCAM diminished
      synaptogenic activity of neuronally expressed PSA-NCAM, suggesting that
      interaction of NCAM with heparan sulfate proteoglycans mediates this activity.
      PSA-NCAM-driven synaptogenesis was also blocked by antagonists to fibroblast
      growth factor receptor and NMDA subtype of glutamate receptors but not by
      blockers of non-NMDA glutamate receptors and voltage-dependent Na+ channels.
      Enzymatic removal of PSA and heparan sulfates also blocked the increase in the
      number of perforated spine synapses associated with NMDA receptor-dependent LTP
      in the CA1 region of organotypic hippocampal cultures. Thus, neuronal PSA-NCAM in
      complex with heparan sulfate proteoglycans promotes synaptogenesis and activity
      dependent remodeling of synapses.

PMID- 15496674
TI  - Induction of a parafacial rhythm generator by rhombomere 3 in the chick embryo.
AB  - Observations of knock-out mice suggest that breathing at birth requires correct
      development of a specific hindbrain territory corresponding to rhombomeres (r) 3
      and 4. Focusing on this territory, we examined the development of a neuronal
      rhythm generator in the chick embryo. We show that rhythmic activity in r4 is
      inducible after developmental stage 10 through interaction with r3. Although the
      nature of this interaction remains obscure, we find that the expression of
      Krox20, a segmentation gene responsible for specifying r3 and r5, is sufficient
      to endow other rhombomeres with the capacity to induce rhythmic activity in r4.
      Induction is robust, because it can be reproduced with r2 and r6 instead of r4
      and with any hindbrain territory that normally expresses Krox20 (r3, r5) or can
      be forced to do so (r1, r4). Interestingly, the interaction between r4 and r3/r5
      that results in rhythm production can only take place through the anterior border
      of r4, revealing a heretofore unsuspected polarity in individual rhombomeres. The
      r4 rhythm generator appears to be homologous to a murine respiratory parafacial
      neuronal system developing in r4 under the control of Krox20 and Hoxa1. These
      results identify a late role for Krox20 at the onset of neurogenesis.

PMID- 15496675
TI  - A functional role of postsynaptic density-95-guanylate kinase-associated protein
      complex in regulating Shank assembly and stability to synapses.
AB  - Postsynaptic density (PSD) proteins include scaffold, cytoskeletal, and signaling
      proteins that structurally and functionally interact with glutamate receptors and
      other postsynaptic membrane proteins. The molecular mechanisms regulating the
      assembly of PSD proteins and their associations with synapses are still widely
      unknown. We investigated the molecular mechanisms of Shank1 targeting and synapse
      assembly by looking at the function of guanylate kinase-associated protein (GKAP)
      and PSD-95 interactions. Shank1 when it is not associated to GKAP, which binds to
      the Shank PSD-95-Discs Large-zona occludens-1 domain, forms filamentous and
      fusiform structures in which the Src homology 3 domain specifically interacts
      with the ankyrin repeat domain, thus allowing its multimerization via a novel
      form of intermolecular interaction. Surprisingly, in both COS-7 cells and
      hippocampal neurons, GKAP forms insoluble aggregates with Shank that colocalize
      with heat shock protein 70 and neurofilaments, two markers of the aggresomes in
      which misfolded proteins accumulate. However, the two proteins are organized in
      clusters in COS cells and synaptic clusters in neurons when both are
      overexpressed and associated with wild-type PSD-95, but not with palmitoylation
      deficient PSD-95. Synaptic activity in neurons induces the formation of Shank and
      GKAP intracellular aggregation and degradation. Similarly, the overexpression of
      a GKAP mutant that is incapable of binding PSD-95 induces Shank aggregation and
      degradation in neurons. Our data suggest a possible functional and structural
      role of the PSD-95-GKAP complex in Shank and PSD protein assembly and stability
      to synapses.

PMID- 15496676
TI  - Neurotrophin-3 reverses chronic mechanical hyperalgesia induced by intramuscular
      acid injection.
AB  - Injection of acid into the gastrocnemius muscle results in a persistent,
      mechanical hyperalgesia of the hindpaw (Sluka et al., 2001). Here, the ability of
      neurotrophins to alter the development of this secondary hyperalgesia was
      assessed using transgenic mice and exogenous neurotrophin administration. Acid
      induced hyperalgesia was measured in wild-type and transgenic mice that
      overexpress neurotrophin-3 (NT-3) in muscle (myo/NT-3 mice). Mechanical and
      thermal sensitivity of the hindpaws were assessed after injections of acidic
      saline, pH 4, into the right medial gastrocnemius. Wild-type mice exhibited
      mechanical but not thermal hyperalgesia in both paws 1 d after acid injection. In
      contrast, myo/NT-3 mice developed a transient mechanical hyperalgesia in both
      paws that disappeared by 2-3 d. The reversal of hyperalgesia in myo/NT-3 mice
      could be mimicked by intramuscular administration of exogenous NT-3 to acid
      injected mice but not by other neurotrophins. The route of NT-3 administration
      appears critical, because intrathecal or intraperitoneal delivery were
      ineffective. The hyperalgesia could only be reversed by NT-3 treatment concurrent
      with acid injection and not after the emergence of hyperalgesia. The acid-induced
      hyperalgesia did not redevelop after the termination of NT-3 treatment,
      suggesting that NT-3 permanently reversed the hyperalgesia. Consistent with the
      behavioral data, paw palpation of acid-injected mice significantly increased Fos
      expression in the spinal cord of wild-type but not myo/NT-3 or NT-3-injected
      mice. The attenuation of hyperalgesia suggests that NT-3 may be a modulator of
      muscle-derived pain, and NT-3 may suppress events that lead to secondary
      hyperalgesia triggered by insult to muscle afferents.

PMID- 15496677
TI  - Time-dependent alterations in mRNA expression of brain neuropeptides regulating
      energy balance and hypothalamo-pituitary-adrenal activity after withdrawal from
      intermittent morphine treatment.
AB  - Chronic stressors alter brain function and may leave traces after their relief.
      We used intermittent morphine treatment to examine the relationships between
      stress-induced changes in energy balance and hypothalamo-pituitary-adrenal (HPA)
      activity and the recovery thereafter. We studied the effects of morphine
      injections on energy balance, hormones and fat stores, brain neuropeptide
      expression, and the ACTH and corticosterone responses to restraint 12 hr after
      the final injection and 8 d later during recovery. Weight gain, food intake, and
      caloric efficiency decreased at morphine onset, and these were maintained
      throughout the morphine injections. At 12 hr, fat stores, leptin, insulin, and
      testosterone concentrations were reduced. Subsequently, body weight gain and food
      intake increased and caloric efficiency was above control during the final days.
      By the eighth recovery day, fat stores and peripheral hormones were no longer
      depressed. At 12 hr, an over-response of CRF mRNA to restraint occurred in the
      hypothalamus, similar to the facilitated ACTH and corticosterone responses. On
      day 8, the hypothalamic CRF mRNA response to restraint was still facilitated,
      opposite to inhibited ACTH responses. Hypothalamic CRF mRNA correlated highly
      with mesenteric fat weight in morphine-treated rats. We conclude that there is a
      prolonged recovery from chronic stressors involving interrelated changes in
      energy balance and HPA activity. Nonetheless, 8 d after withdrawal from morphine,
      rats still display facilitated central stress responses, similar to the HPA
      symptoms described in posttraumatic stress disorder patients. Repeated partial
      withdrawal associated with intermittent morphine treatment, compounded by
      complete withdrawal associated with termination of the treatment, is likely
      required for these metabolic and HPA derangements.

PMID- 15496678
TI  - Rapid, activity-induced increase in tissue plasminogen activator is mediated by
      metabotropic glutamate receptor-dependent mRNA translation.
AB  - Long-term synaptic plasticity is both protein synthesis-dependent and synapse
      specific. Therefore, the identity of the newly synthesized proteins, their
      localization, and mechanism of regulation are critical to our understanding of
      this process. Tissue plasminogen activator (tPA) is a secreted protease required
      for some forms of long-term synaptic plasticity. Here, we show tPA activity is
      rapidly increased in hippocampal neurons after glutamate stimulation. This
      increase in tPA activity corresponds to an increase in tPA protein synthesis that
      results from the translational activation of mRNA present at the time of
      stimulation. Furthermore, the mRNA encoding tPA is present in dendrites and is
      rapidly polyadenylated after glutamate stimulation. Both the polyadenylation of
      tPA mRNA and the subsequent increase in tPA protein is dependent on metabotropic
      glutamate receptor (mGluR) activation. A similar mGluR-dependent increase in tPA
      activity was detected after stimulation of a synaptic fraction isolated from the
      hippocampus, suggesting tPA synthesis is occurring in the synaptodendritic
      region. Finally, we demonstrate that tPA mRNA is bound by the mRNA-binding
      protein CPEB (cytoplasmic polyadenylation element binding protein-1), a protein
      known to regulate mRNA translation via polyadenylation. These results indicate
      that neurons are capable of synthesizing a secreted protein in the synaptic
      region, that mGluR activation induces mRNA polyadenylation and translation of
      specific mRNA, and suggest a model for synaptic plasticity whereby translational
      regulation of an immediate early gene precedes the increase in gene
      transcription.

PMID- 15496679
TI  - Early and progressive sensorimotor anomalies in mice overexpressing wild-type
      human alpha-synuclein.
AB  - Accumulation of alpha-synuclein in brain is a hallmark of synucleinopathies,
      neurodegenerative diseases that include Parkinson's disease. Mice overexpressing
      alpha-synuclein under the Thy-1 promoter (ASO) show abnormal accumulation of
      alpha-synuclein in cortical and subcortical regions of the brain, including the
      substantia nigra. We examined the motor deficits in ASO mice with a battery of
      sensorimotor tests that are sensitive to alterations in the nigrostriatal
      dopaminergic system. Male wild-type and ASO mice were tested every 2 months for 8
      months for motor performance and coordination on a challenging beam, inverted
      grid, and pole, sensorimotor deficits in an adhesive removal test, spontaneous
      activity in a cylinder, and gait. Fine motor skills were assessed by the ability
      to grasp cotton from a bin. ASO mice displayed significant impairments in motor
      performance and coordination and a reduction in spontaneous activity as early as
      2 months of age. Motor performance and coordination impairments became
      progressively worse with age and sensorimotor deficits appeared at 6 months. Fine
      motor skills were altered at 4 months and worsened at 8 months. These data
      indicate that overexpression of alpha-synuclein induced an early and progressive
      behavioral phenotype that can be detected in multiple tests of sensorimotor
      function. These behavioral deficits provide a useful way to assess novel drug
      therapy in genetic models of synucleinopathies.

PMID- 15496680
TI  - Pronounced cell death in the absence of NMDA receptors in the developing
      somatosensory thalamus.
AB  - Genetic deletion of NMDA glutamate receptors disrupts development of whisker
      related neuronal patterns in the somatosensory system. Independent studies have
      shown that NMDA receptor antagonists increase cell death among developing
      neurons. Here, we report that a dramatic feature of the developing somatosensory
      system in newborn NMDA receptor 1 (NMDAR1) knock-out mice is increased cell death
      in the ventrobasal nucleus (VB) of the thalamus. Sections were subject to
      terminal deoxynucleotidyl transferase dUTP nick end labeling staining for
      apoptotic DNA fragmentation, thionine staining for pyknotic nuclei, silver
      staining for degenerating cells, and immunostaining for caspase-3. All four
      methods demonstrated that deletion of NMDAR1 causes a large (on the order of
      threefold to fivefold) increase in cell death in the VB. The NMDA receptor
      antagonists dizocilpine maleate (MK-801) and phencyclidine also increase cell
      death in this structure. The onset of increased cell death in the VB in the
      absence of NMDA receptor function is approximately the time of birth, overlaps
      with naturally occurring cell death and synaptogenesis, and displays some
      anatomical specificity. For example, there was no increase in cell death in the
      hippocampus or neocortex of NMDAR1 knock-out mice at any of the time points
      examined: embryonic day 15.5 (E15.5), E17.5, and postnatal day 0. We also report
      a significant reduction in the size of the VB that is evident starting at E17.5.
      The results indicate that NMDA receptors play a major role in cell survival
      during naturally occurring cell death in the VB and demonstrate that cell death
      is a consideration in NMDA receptor knock-out studies.

PMID- 15496681
TI  - Olfactory sex discrimination persists, whereas the preference for urinary
      odorants from estrous females disappears in male mice after vomeronasal organ
      removal.
AB  - Based on observed changes in the social context for the display of ultrasonic
      vocalizations, scent marking, aggression, and mounting behavior by male mice with
      a null mutation of the transient receptor potential 2 ion channel, it was
      proposed recently that a primary function of the mouse vomeronasal organ
      (VNO)/accessory olfactory system is sex discrimination. We tested this hypothesis
      directly by studying the ability of male mice to discriminate between urinary
      odors of conspecifics of the two sexes and in different endocrine states using
      habituation-dishabituation tests. Male mice from which the VNO had been
      surgically removed (VNOx) resembled sham-operated controls (VNOi) in their
      ability to discriminate between volatile urinary odors from estrous females
      versus gonadally intact males, as well as between urinary odors from estrous
      versus ovariectomized females and from gonadally intact versus castrated males.
      When physical access to stimuli was permitted, VNOi control males strongly
      preferred to investigate volatile and nonvolatile urinary odorants from estrous
      females as opposed to intact males, whereas VNOx males showed no such preference.
      Mating performance in tests with estrous females was equivalent in VNOi and VNOx
      subjects. Both groups of males preferred to mount an estrous female instead of a
      castrated male. Our results suggest that the VNO is not required for sex
      discrimination but instead detects the nonvolatile components of opposite-sex
      urine that may be used to help prolong contact with individuals that produce
      these chemosignals.

PMID- 15496682
TI  - Metaplastic facilitation and ultrastructural changes in synaptic properties are
      associated with long-term modulation of the lamprey locomotor network.
AB  - The neuropeptide substance P evokes a long-term protein synthesis-dependent
      increase in the cycle frequency of locomotor network activity in the lamprey.
      Although cellular and synaptic mechanisms that could induce this effect have been
      identified, nothing is known of the underlying maintenance mechanisms. These
      mechanisms have been examined here. Substance P potentiates low-frequency-evoked
      EPSPs from excitatory network interneurons. It also converts the depression of
      the EPSP during spike trains into facilitation, an example of metaplasticity. The
      metaplasticity was associated with a reduction of the transmitter release
      probability but an increase in the number of release sites. Although the
      potentiation of low-frequency-evoked EPSPs recovered within 1 hr, the metaplastic
      facilitation had not recovered 3-4 hr after substance P application. The
      metaplasticity thus extended into the protein synthesis-dependent maintenance
      phase of the network modulation, making it the only identified cellular or
      synaptic effect of substance P to last this long. It also had the same induction
      and maintenance features as the network burst frequency modulation, further
      suggesting that the two effects were related. Long-term changes in synaptic
      properties are often associated with changes in synaptic organization. We have
      thus also examined the effects of substance P on synaptic ultrastructure up to 5
      hr after substance P application. Substance P had several significant effects.
      These included an increase in the number of docked vesicles and a reduction of
      the synaptic gap. Substance P thus has long-term effects on synaptic organization
      and function. The relevance of these effects to the long-term locomotor network
      modulation is discussed.

PMID- 15496684
TI  - Acute medicine: past, present, and future.

PMID- 15496685
TI  - Changes and thanks.

PMID- 15496686
TI  - Should etomidate be the induction agent of choice for rapid sequence intubation
      in the emergency department?
AB  - The ideal induction agent for emergency airway management should be rapidly
      acting, permit optimum intubating conditions, and be devoid of significant side
      effects. This review was performed to ascertain whether etomidate should be the
      induction agent of choice for rapid sequence intubation (RSI) in the emergency
      department, specifically examining its pharmacology, haemodynamic profile, and
      adrenocortical effects. A search of Medline (1966-2002), Embase (1980-2002), the
      Cochrane controlled trials register, and CINAHL was performed. In addition, the
      major emergency medicine and anaesthesia journals were hand searched for relevant
      material. Altogether 144 papers were identified of which 16 were relevant. Most
      studies were observational studies or retrospective reviews with only one double
      blind randomised controlled trial and one un-blinded randomised controlled trial.
      Appraisal of the available evidence suggests that etomidate is an effective
      induction agent for emergency department RSI; it has a rapid onset of anaesthesia
      and results in haemodynamic stability, even in hypovolaemic patients or those
      with limited cardiac reserve. Important questions regarding the medium to long
      term effects on adrenocortical function (even after a single dose) remain
      unanswered.

PMID- 15496687
TI  - Impact of a severe acute respiratory syndrome outbreak in the emergency
      department: an experience in Taiwan.
AB  - OBJECTIVES: To evaluate the impact of a severe acute respiratory syndrome (SARS)
      outbreak in the emergency department (ED). METHODS: Computerised records of all
      ED visits in January and May 2003 were analysed and compared, representing before
      and during the SARS epidemic respectively. Data were grouped into two categories.
      Group 1 was the indicators of impact on patients, including visitor's condition
      classification, number of patients that died on arrival (DOA), received
      cardiopulmonary resuscitation, underwent endotracheal intubation, needed
      mechanical ventilation, discharged against medical advice (AAD), died in the ED,
      and the admission rate to wards. Group 2 was the indicators of impact on the
      quality of medical care, including number of visits that returned within 72 hours
      (early returns), underwent chest radiography, upper abdomen sonography or
      computed tomography, and the length of stay. RESULTS: There were 6650 and 3901
      consecutive encounters in January and May 2003 respectively. There were
      significant differences on condition classifications (p = 0.000), increased rate
      of patients that underwent endotracheal intubation (p = 0.003), needed mechanical
      ventilation (p = 0.020), and admission (p = 0.000). The rate of AAD decreased
      significantly (p = 0.024). There was no significant difference on early returns,
      although the length of stay in the ED increased (p = 0.043). The number of visits
      that underwent chest radiological examination increased (p = 0.000) and upper
      abdomen sonography (p = 0.007) decreased significantly in May. CONCLUSIONS: SARS
      had an impact on the medical service system and decreased visits by 40% in the
      ED. Patients visiting the ED had more severe conditions than before. The impact
      of SARS on quality of medical care can be minimised when adequate infection
      control measures are applied.

PMID- 15496688
TI  - Evaluation of the Simplify D-dimer assay as a screening test for the diagnosis of
      deep vein thrombosis in an emergency department.
AB  - OBJECTIVES: To evaluate the use in an emergency department of a new D-dimer assay
      (Simplify D-dimer) as a screening test for deep vein thrombosis (DVT). METHODS:
      187 outpatients with clinical features suspicious of acute DVT were entered into
      this study. A Simplify D-dimer test was performed in the emergency department on
      all patients. A SimpliRED D-dimer test and a semi-automated latex agglutination
      assay (Auto-D-dimer 700 on a Thromboscreen 400C analyser) were performed in the
      haematology laboratory. All patients were investigated with contrast venography
      to confirm or exclude the diagnosis of DVT. RESULTS: The Simplify test had a
      sensitivity of 94.1% and a negative predictive value (NPV) of 94.8%. These
      results compared favourably with the SimpliRED test (sensitivity 74.5%, NPV
      89.7%) and the latex agglutination assay (sensitivity 90.2%, NPV 92.2%). This
      increased sensitivity was at the cost of a lower specificity, the specificity of
      the three d-dimer tests being Simplify 40.4%, SimpliRED 83.1%, and latex
      agglutination 43.4%. CONCLUSIONS: Simplify proved to be a rapid and easy to use
      test and may be useful for use in the emergency department as part of a
      diagnostic algorithm for deep vein thrombosis. Further larger scale studies are
      needed.

PMID- 15496689
TI  - ACCESS: the acute cerebral CT evaluation stroke study.

PMID- 15496690
TI  - Patients with community acquired pneumonia discharged from the emergency
      department according to a clinical practice guideline.
AB  - OBJECTIVES: To assess the safety of discharging patients with community acquired
      pneumonia (CAP) according to a clinical practice guideline. METHODS: A systematic
      retrospective review of medical records of 867 adult patients discharged from an
      emergency department (ED) with CAP between 3 January 1999 and 3 January 2001.
      Readmission or death rates within 30 days of discharge were evaluated, using data
      from all local hospitals and from the provincial coroner. RESULTS: Of 685
      patients with pneumonia severity index (PSI) scores of <91, 13 (1.9%) were
      readmitted and five (0.76%) died within 30 days of the ED visit. Thirty day
      readmission and death rates for patients with PSI >90 were 7.14% (13 of 182) and
      9.34% (17 of 182), respectively. CONCLUSION: Adult patients with CAP discharged
      from the ED according to the recommendations of a clinical practice guideline
      based on the PSI have low readmission and death rates, and are generally safely
      managed as outpatients.

PMID- 15496691
TI  - Heliox in the treatment of chronic obstructive pulmonary disease.
AB  - OBJECTIVE: To determine if breathing helium oxygen mixtures in addition to
      conventional therapy in non-intubated adult chronic obstructive airways disease
      (COPD) patients reduces the arterial partial pressure of carbon dioxide (Paco(2))
      more than conventional treatment alone, and confers an advantage in terms of the
      odds of intubation in the acute setting. DESIGN: Meta-analysis. SETTING: Diverse
      settings. PARTICIPANTS: Adult patients with a diagnosis of either stable severe
      or acute COPD. MAIN OUTCOME MEASURES: Decrease in partial pressure of arterial
      Paco(2) and intubation rates. RESULTS: Combination of the results from trials
      measuring change in Paco(2) in COPD subjects receiving conventional therapy but
      breathing helium-oxygen estimated a reduction of 0.78 KPa (1.44-0.13) beyond that
      produced by conventional therapy with air-oxygen breathing (n = 234). Using
      quantitative and qualitative measures of validity it was found that most trials
      were unsatisfactory. Chief concerns were poor concealment of allocation and lack
      of blinding. Analysis excluding all papers with low methodological quality
      (Jadad<2) estimated the reduction in Paco(2) conferred by use of Heliox breathing
      to be 0.22 KPa (+0.57 to -0.14). A non-significant reduction (p = 0.2). When
      combined, the results from trials measuring the intubation rates of patients
      treated conventionally or with Heliox (n = 121) the odds ratio of intubation was
      0.096 (0.03-0.27). CONCLUSION: Definitive evidence of a beneficial role of Heliox
      in treatment of severe COPD is lacking and therefore its wide scale use cannot be
      recommended based on this analysis. However, as a beneficial effect of Heliox
      breathing was reported in all trials, further investigation with a well conducted
      randomised controlled trial is warranted.

PMID- 15496693
TI  - A paradigm shift in the nature of care provision in emergency departments.
AB  - OBJECTIVES: Access block to acute hospital inpatient beds has pressured emergency
      departments (EDs) to develop strategies to facilitate the management of patients
      in the community (new services) and to streamline ED care (facilitative
      initiatives). The aim of this study was to determine the nature and extent of
      those strategies introduced into the 17 public hospital EDs in Melbourne,
      Australia, since 1998. METHODS: This was a cross sectional survey of ED directors
      and/or nurse unit managers undertaken in November and December, 2002. Face to
      face or telephone interviews were conducted using a researcher administered
      questionnaire. RESULTS: All 17 EDs participated. A total of 15 strategies had
      been introduced into 15 (88.2%) EDs. New services included care coordination
      teams (12 ED, 70.6%), short stay units (10, 58.8%), psychiatric services (10,
      58.8%), chest pain units (7, 41.2%), pharmacy services (3, 17.7%), sexual assault
      service (1, 5.9%), and hospital in the home within the ED (1, 5.9%). Facilitative
      initiatives included nurse initiated management (12, 70.6%), fast track processes
      (10, 58.8%), multidisciplinary triage (4, 23.5%), disposition
      nurses/communication clerks (3, 17.7%), and day treatment clinics (2, 11.8%).
      CONCLUSIONS: Melbourne's EDs have adapted rapidly to external pressures of access
      block and increasing patient numbers. Many traditional inpatient services have
      now been incorporated into the EDs. These EDs now provide a different and
      expanded paradigm of care.

PMID- 15496692
TI  - Emergency department thrombolysis improves door to needle times.
AB  - OBJECTIVE: To identify the effect on door to needle (DTN) time of moving the site
      of thrombolysis delivery from the coronary care unit (CCU) to the emergency
      department (ED). To ascertain if moving the site of thrombolysis enables
      appropriate use of thrombolysis. DESIGN: Prospective cohort study. SETTING: CCU
      and ED of a 450 bed Scottish district general hospital without on-site primary
      angioplasty. PARTICIPANTS: Primary site for thrombolysis of patients presenting
      to the hospital with ST elevation MI (STEMI) moved from CCU to ED on 1 April
      2000. Study patients who had a confirmed STEMI and/or received thrombolytic
      therapy before this date were defined as the pre-change group; those who were
      diagnosed as STEMI and/or received thrombolytic therapy after this date were
      defined as the post-change group. STATISTICAL ANALYSIS: Mann-Whitney test was
      used to compare medians and chi(2) test for categorical data. RESULTS: 1349
      patients were discharged from CCU with a diagnosis of STEMI or received
      thrombolysis in the ED or CCU between April 1998 and April 2002. There were 632
      patients in the pre-change group and 654 patients in the post-change group. Sixty
      three patients were excluded. Median DTN time for the pre-change group (321
      thrombolysed patients) was 64 minutes and median DTN time for the post-change
      group (324 thrombolysed patients) was 35 minutes, a median difference of 25
      minutes (95% CI for difference 20 to 29 minutes, p<0.0001, Mann-Whitney U test).
      A total of 37 patients were thrombolysed but did not have a final diagnosis of
      STEMI. CONCLUSION: A significant reduction in DTN times accompanied this change
      in practice in this hospital.

PMID- 15496694
TI  - Reviewing emergency care systems I: insights from system dynamics modelling.
AB  - OBJECTIVES: To describe the components of an emergency and urgent care system
      within one health authority and to investigate ways in which patient flows and
      system capacity could be improved. METHODS: Using a qualitative system dynamics
      (SD) approach, data from interviews were used to build a conceptual map of the
      system illustrating patient pathways from entry to discharge. The map was used to
      construct a quantitative SD model populated with demographic and activity data to
      simulate patterns of demand, activity, contingencies, and system bottlenecks.
      Using simulation experiments, a range of scenarios were tested to determine their
      likely effectiveness in meeting future objectives and targets. RESULTS: Emergency
      hospital admissions grew at a faster annual rate than the national average for
      1998-2001. Without intervention, and assuming this trend continued, acute
      hospitals were likely to have difficulty sustaining levels of elective work, in
      reaching elective admission targets and in achieving bed occupancy targets.
      General practice admissions exerted the greatest influence on occupancy rates.
      Prevention of emergency admissions for older people (3%-6% each year) reduced bed
      occupancy in both hospitals by 1% per annum over five years. Prevention of
      emergency admissions for patients with chronic respiratory disease affected
      occupancy less noticeably, but because of the seasonal pattern of admissions, had
      an effect on peak winter occupancy. CONCLUSIONS: Modelling showed the potential
      consequences of continued growth in demand for emergency care, but also
      considerable scope to intervene to ameliorate the worst case scenarios, in
      particular by increasing the care management options available in the community.

PMID- 15496695
TI  - Reviewing emergency care systems 2: measuring patient preferences using a
      discrete choice experiment.
AB  - OBJECTIVE: To investigate patients' strength of preferences for attributes
      associated with modernising delivery of out of hours emergency care services in
      Nottingham. METHODS: A discrete choice experiment was applied to quantify
      preferences for key attributes of out of hours emergency care. The attributes
      reflected the findings of previous research, current policy initiatives, and
      discussions with local key stakeholders. A self complete questionnaire was
      administered to NHS Direct callers and adults attending accident and emergency,
      GP services and NHS walk-in centre. Regression analysis was used to estimate the
      relative importance of the different attributes. RESULTS: Response was 74% (n =
      457) although 61% (n = 378) were useable. All attributes were statistically
      significant. Being consulted by a doctor was the most important attribute. This
      was followed by being consulted by a nurse, being kept informed about waiting
      time, and quality of the consultation. Respondents were prepared to wait an extra
      2 hours 20 minutes to be consulted by a doctor. There were no measurable
      preference differences between patients surveyed at different NHS entry points.
      Younger respondents preferred single telephone call access to health care out of
      hours. Although having services provided close to home and making contact in
      person were generally preferred, they were less important than others, suggesting
      that a range of service locations may be acceptable to patients. CONCLUSIONS:
      This study showed that local solutions for reforming emergency out of hours care
      should take account of the strength of patient preferences. The method was
      acceptable and the results have directly informed the development of a local
      service framework for emergency care.

PMID- 15496696
TI  - Use of the patient at risk scores in the emergency department: a preliminary
      study.
AB  - OBJECTIVES: To assess the feasibility of using a modified patient at risk (PAR)
      scoring system in the emergency department. METHODS: Modified PAR scores were
      calculated for 30 triage category 1 and 2 patients on arrival in the department
      and at 15 minutes after the initial resuscitation was underway using observation
      datasheets designed for this project. RESULTS: Three patients (10%) were admitted
      to the intensive care unit (ICU). Twenty six patients (88%) were admitted to a
      general ward and one was discharged. Fifty per cent of the patients had a PAR
      score of 3 or more on arrival. Eighty seven per cent of the general ward patients
      had a PAR score that was stable or improved during the first 15 minutes of
      resuscitation. The other three ward patients, whose scores deteriorated, were
      assessed in the emergency department by the appropriate teams and deemed
      appropriate for ward beds. Two of the three ICU patients deteriorated in the
      resuscitation room. The third ICU patient maintained a PAR score of 2 but had
      such overwhelming injuries that ICU was the only option. DISCUSSION: Serial PAR
      scores are far more informative than isolated scores. This study suggests that
      serial PAR scores could be used in three ways in the emergency department.
      Firstly, in the assessment of individual patients and their response to initial
      resuscitation. Secondly, as a guide to the need further specialist assessment
      before leaving the emergency department. Finally, as an audit tool to measure the
      effectiveness of initial treatments in large numbers of patients during the
      initial resuscitation.

PMID- 15496697
TI  - Midazolam is more likely to cause hypotension than etomidate in emergency
      department rapid sequence intubation.
AB  - OBJECTIVE: To compare the haemodynamic effect of low dose midazolam and etomidate
      as induction agent in emergency department rapid sequence intubation. METHODS: A
      prospective observational study in two phases. In phase one, midazolam 2-4 mg was
      used as induction agent and in phase two, etomidate 0.2-0.3 mg/kg was used. The
      haemodynamic data were recorded before and after intubation for comparison.
      Changes in mean systolic blood pressure were analysed with SPSS software.
      RESULTS: A 10% decrease in mean systolic blood pressure was observed in the
      midazolam group (p = 0.001) while there was no significant change in the
      etomidate group. Some 19.5% of patients had hypotension after being given
      midazolam while only 3.6% with etomidate (p = 0.002). Patients older than 70
      tended to have more hypotension episodes but the difference was not statistically
      significant. CONCLUSIONS: Midazolam, even in low dose, was more likely than
      etomidate to cause significant hypotension when used as an induction agent for
      rapid sequence intubation. Etomidate is a better alternative.

PMID- 15496698
TI  - Research in emergency situations: with or without relatives consent.
AB  - Patients in emergency situations with impaired consciousness are unable to give
      informed consent to participate in clinical trials. In this situation, some
      ethics committees ask that consent is obtained from a relative or a legal
      representative. Others however, waive the need for informed consent and allow the
      doctor in charge to take responsibility for entering such patients. This study
      used data from the MRC CRASH Trial, an international randomised controlled trial
      of corticosteroids in head injury, to assess whether the practice of waiving
      consent results in earlier administration of the trial treatment. It was found
      that time from injury to randomisation was significantly reduced (1.2 hours, 95%
      CI 0.7 to 1.8 hours) and patient recruitment was higher in hospitals where
      consent was waived compared with those that required relatives consent.

PMID- 15496699
TI  - Review of sports injuries presenting to an accident and emergency department.

PMID- 15496700
TI  - Best evidence topic report. Which facial views for facial trauma?
AB  - A short cut review was carried out to establish whether a reduced number of
      facial radiographs had acceptable clinical utility at detecting facial fractures
      after trauma. Altogether 614 papers were found using the reported search, of
      which five 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- 15496702
TI  - Best evidence topic report. Two thumb compared with two finger cardiopulmonary
      resuscitation in infants.
AB  - A short cut review was carried out to establish whether the two thumb technique
      was superior to the two finger technique in delivering effective chest
      compressions in infants with cardiac arrest. Altogether 175 papers were found
      using the reported search, of which four 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- 15496703
TI  - Best evidence topic report. Low molecular weight heparin for intravenous drug
      users with deep vein thrombosis.
AB  - A short cut review was carried out to establish whether low molecular weight
      heparins were safer and more effective anticoagulants than coumarins in injecting
      drug users (IDUs) with deep venous thrombosis (DVT). Altogether 276 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- 15496704
TI  - Best evidence topic report. Non-steroidal anti-inflammatory drugs and
      exacerbations of asthma in children.
AB  - A short cut review was carried out to establish whether non-steroidal anti
      inflammatory agents cause exacerbations of asthma in children. Altogether 301
      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- 15496705
TI  - Best evidence topic report. Thrombotic complications of a femoral central venous
      catheter.
AB  - A short cut review was carried out to establish whether the insertion of a
      femoral central venous pressure line causes more thrombotic complications than
      insertion of a jugular line. Altogether 90 papers were found using the reported
      search, of which eight 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- 15496706
TI  - Best evidence topic report. Suicide at christmas.
AB  - A short cut review was carried out to establish whether the risk of suicide and
      parasuicide increases at Christmas. Fifteen papers were found using the reported
      search, of which six 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- 15496707
TI  - SOCRATES 2 (synopsis of Cochrane reviews applicable to emergency services).

PMID- 15496708
TI  - Impact of "dual response" on prehospital thrombolysis in remote and rural areas
      of Scotland: prospective observational study.

PMID- 15496709
TI  - Does setting up out of hours primary care cooperatives outside a hospital reduce
      demand for emergency care?
AB  - OBJECTIVE: To investigate whether the reorganisation of out of hours primary
      care, from practice rotas to GP cooperatives, changed utilisation of primary and
      hospital emergency care. METHODS: During a four week period before and a four
      week period after the reorganisation of out of hours primary care in a region in
      the south of the Netherlands all patient contacts with general practitioners and
      hospital accident and emergency (A&E) departments were analysed. RESULTS: A 10%
      increase was found in patient contacts with out of hours primary care, and a 9%
      decrease in patient contacts with out of hours emergency care. The number of self
      referrals at the A&E department was reduced by about 4%. CONCLUSIONS: The
      reorganisation of out of hours primary care has led to a shift in patient
      contacts from emergency care to primary care.

PMID- 15496710
TI  - Developing alternative ambulance response schemes: analysis of attitudes,
      barriers, and change.
AB  - OBJECTIVES: Alternative response schemes for emergency calls are being set up by
      many UK ambulance services. The barriers to such developments from the
      perspective of ambulance service staff have not been formally investigated. The
      aims of this study are to identify attitudes and barriers to the development of
      alternative response schemes and ways of easing the transition as they are
      implemented. METHODS: South Yorkshire Ambulance Service crews and control room
      staff were interviewed, using South Yorkshire's paramedic practitioner (PP)
      scheme as a model of an alternative response scheme. RESULTS: 55 ambulance crew
      and 17 control staff were interviewed. Most (97%, n = 70) thought that the PP
      scheme was a good way of dealing with patients who call 999 but may not need
      urgent transport and hospital treatment. The perceived effect of the PP scheme on
      traditional ambulance service duties was equally divided between a third who
      thought there had been no effect, a third who perceived an improvement, and a
      third a deterioration. Recurrent difficulties with the scheme were found relating
      to the AMPDS methodology of ambulance dispatch, and ambulance service performance
      targets. CONCLUSIONS: Flexibility of AMPDS and dispatch targets will need to be
      reviewed to permit the successful implementation of alternative responses to 999
      calls. Careful consideration needs to be given to communicating the aims and
      value of such schemes to all staff and ensuring a common understanding of, and
      commitment to, a shared vision. The effect of implementation on the remaining
      service function must be well planned.

PMID- 15496711
TI  - 8 management of allergy, rashes, and itching.

PMID- 15496712
TI  - Cardiac emergencies caused by honey ingestion: a single centre experience.
AB  - An unusual type of food poisoning is commonly seen in the Black Sea coast of
      Turkey attributable to andromedotoxin containing toxic honey ingestion. This
      study is a retrospective case series of 19 patients admitted to an emergency
      department in 2002, poisoned by "mad" honey. All of the patients had the
      complaints of nausea, vomiting, sweating, dizziness, and weakness, several hours
      after ingesting "mad" honey. Physical examination showed hypotension in 15
      patients, sinus bradycardia in 15, and complete atrioventricular block (AVB) in
      four patients on admission. Two patients with bradycardia and two with AVB fell
      and injured their heads. Three of them presented with local haematoma. One
      patient had a 6 cm cut on his head without any neurological deficit and his
      cranial computed tomography imaging was normal. Hypotension and conduction
      disorders resolved with atropine treatment, resulting in complete recovery within
      24 hours.

PMID- 15496713
TI  - Atrial fibrillation after electrical shock: a case report and review.
AB  - A 52 year old man was admitted to an emergency department with a fast ventricular
      rate atrial fibrillation after an electrical shock. Electrical cardioversion was
      attempted after echocardiographic examination. This failed, but the heart rate
      slowed. Successful pharmacological cardioversion was achieved after 16 hours of
      amiodarone infusion. Pre-excitation syndrome was detected on baseline
      echocardiograph. Serum cardiac specific markers were all within normal limits. No
      abnormal findings were detected by chest radiography, echocardiographic, or
      coronary angiographic investigations. Acute onset atrial fibrillation after
      electrical injury is discussed.

PMID- 15496714
TI  - Postnatal pre-cordial pain. Pulmonary embolism or peripartum cardiomyopathy.

PMID- 15496715
TI  - Hard to swallow: an unusual complication of thrombolysis.

PMID- 15496716
TI  - Congenital para-oesophageal hiatus hernia: an interesting family history.

PMID- 15496717
TI  - Lightning: an unusual cause of cerebellar infarction.
AB  - The neurological complications of lightning injury are not infrequent. However,
      scarce data are available on cerebellar infarction attributable to lightning
      injury. A 45 year old man was admitted to the emergency department because of
      lightning injury. The patient had a Glasgow coma scale score of 13/15 on arrival
      at hospital with accompanying dysarthria and hypotonia. Computed tomography of
      the head showed only a mild cerebral oedema. Ataxia was recorded on the fourth
      day. Magnetic resonance imaging of the head showed ischaemia predominantly in the
      cerebellar hemispheres bilaterally and in the parietal, temporal, and frontal
      lobes on the right. Anti-oedema treatment was started. The patient was discharged
      after seven days. After one month the patient was re-examined and found to have
      minimal ataxia and dysarthria. Lightning injury should not be overlooked in the
      aetiology and differential diagnosis of acute cerebellar ischaemic insult and
      relevant clinical findings in adults.

PMID- 15496718
TI  - Acute urinary retention attributable to sacral herpes zoster.
AB  - Acute urinary retention in women is uncommon. A 63 year old woman presented with
      suprapubic pain, a palpable bladder, and multiple grouped vesicles on the right
      buttock. Catheterisation showed a residual of 2000 ml. A case is reported of
      acute urinary retention secondary to herpes zoster infection of the sacral nerves
      (S2-4).

PMID- 15496719
TI  - Aetiology of cerebral oedema in diabetic ketoacidosis.

PMID- 15496720
TI  - The hidden dangers of dietary supplements.

PMID- 15496721
TI  - What to do about psychological distress in emergency department senior house
      officers?

PMID- 15496722
TI  - Emergency management of contact lens associated corneal abrasions.

PMID- 15496723
TI  - Glucagon use in symptomatic beta blocker overdose.

PMID- 15496724
TI  - RNA interference silencing the transcriptional message: aspects and applications.
AB  - RNA interference (RNAi) is silencing of gene expression by double-stranded RNA
      (dsRNA) having complementary sequence to the target gene to be silenced. This
      phenomenon has transformed into a complete technology for functional genomic
      studies. Small interfering RNAs (siRNAs) are 21- to 23-nucleotide dsRNAs, in
      which the sense strand is the same as the target mRNA and the antisense strand is
      the complement of the target mRNA sequence. These are the effector molecules for
      inducing RNAi, leading to posttranscriptional gene silencing with RNA-induced
      silencing complex. Besides siRNA, which can be chemically synthesized, various
      other systems in the form of potential effector molecules for posttranscriptional
      gene silencing are available, such as short hairpin RNAs (shRNAs), long dsRNAs,
      short temporal RNAs, and micro RNAs (miRNAs). These effector molecules either are
      processed into siRNA such as in the case of shRNA or directly aid gene silencing
      as in the case of miRNA. RNAi for various unknown genes may facilitate to
      elucidate inherited genetic diseases and provide drug candidates for viral and
      oncogenic diseases. This can be achieved by targeting mRNA from oncogenic genes
      or mRNA for viral cellular receptor and viral structural proteins for RNAi. In
      this article, we evaluate various aspects and applications of RNAi technology and
      provide comprehensive information for the system currently available for inducing
      RNAi.

PMID- 15496725
TI  - Effect of detoxification of dilute-acid corn fiber hydrolysate on xylitol
      production.
AB  - Four different detoxification methods were evaluated for the production of
      xylitol from corn fiber dilute-acid hydrolysate using Candida tropicalis.
      Although C. tropicalis could ferment the dilute partially neutralized hydrolysate
      to xylitol in low yields (0.1 g/g), it could not ferment the concentrated
      hydrolysate. Overliming, calcium hydroxide neutralization, neutralization
      combined with activated charcoal, and overliming combined with activated charcoal
      methods were used to improve the fermentation of the concentrated hydrolysates.
      The partial neutralization combined with activated charcoal treatment was the
      most effective method with respect to xylitol yield and productivity. The highest
      xylitol yield (0.4 g of xylitol/g of xylose) was obtained for the highest
      concentration of hydrolysate (three times the original) that had been treated
      with calcium hydroxide and activated charcoal. The corresponding productivity was
      0.23 g/(L x h). Overliming caused reduction in xylitol yield.

PMID- 15496726
TI  - Decolorization and partial degradation of selected azo dyes by methanogenic
      sludge.
AB  - The toxicity potential and decolorization of three acid azo dyes (Acid Orange 6,
      Acid Orange 7, and Acid Orange 52) by methanogenic granular sludge from an
      anaerobic expanded granular sludge bed reactor was assayed. Complete bioreduction
      was found for all three azo dyes. Sulfanilic acid and 4-aminoresorcinol were
      detected from the decolorization of Acid Orange 6, sulfanilic acid and 1-amino-2
      naphtol were detected from the reduction of Acid Orange 7, and sulfanilic acid
      and N,N-dimethyl-1,4-phenylenediamine (DMP) were found to be intermediates of
      Acid Orange 52 degradation. Sulfanilic acid and 1-amino-2-naphtol were persistent
      in the anaerobic conditions, whereas 4-aminoresorcinol was completely mineralized
      by anaerobic sludge and DMP was transformed into 1,4-phenylenediamine. Enrichment
      cultures obtained via consecutive passages on basal medium with only azo dye as a
      carbon and an energy source seemed to be morphologically heterogeneous.
      Baculiform and coccus cells were found when viewed under a light microscope.
      Cocci were joined in chains. Because anaerobic sludge contains sulfate-reducing
      bacteria and therefore may generate sulfide, azo dyes were tested for chemical
      decolorization by sulfide to compare rates of chemical and biologic reduction.

PMID- 15496727
TI  - Purification, characterization, and structural investigation of a new moderately
      thermophilic and partially calcium-independent extracellular alpha-amylase from
      Bacillus sp. TM1.
AB  - A new alpha-amylase was extracted from a recently found strain of Bacillus sp.
      and purified by ion-exchange chromatography. Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis showed a single band for the purified enzyme
      with an apparent molecular weight of 59 kDa. The optimum temperature and pH range
      of the enzyme were 40-60 degrees C and 4.5-7.5, respectively, and its activation
      energy was 1.974 kcal/mol. The Km value for the enzyme activity on soluble starch
      was 4 mg/mL, and the Tm values obtained from the circular dichroism (CD) results
      of thermal unfolding were 78.7 and 80.2 degrees C in the absence and presence of
      the calcium, respectively. The enzyme was almost completely inhibited by the
      addition of Fe3+, Mn2+, and Zn2+ and was activated by EDTA, Cr3+, and Al3+.
      Moreover, it was partially inhibited by Ca2+, Ba2+, Ni2+, and Co2+. Proteolytic
      digestion of the enzyme using trypsin combined with results from Tm using CD and
      irreversible thermoinactivation suggests that this enzyme can be considered a
      moderate thermophile with both mild flexibility and rigidity.

PMID- 15496728
TI  - High-cell-density cultivation of Pseudomonas putida IPT 046 and medium-chain
      length polyhydroxyalkanoate production from sugarcane carbohydrates.
AB  - We studied high-density cultures of Pseudomonas putida IPT 046 for the production
      of medium-chain-length polyhydroxyalkanoates (PHAMCL) using an equimolar mixture
      of glucose and fructose as carbon sources. Kinetics studies of P. putida growth
      resulted in a maximum specific growth rate of 0.65 h(-1). Limitation and
      inhibition owing to NH4+ ions were observed, respectively, at 400 and 3500 mg of
      NH4+/L. The minimum concentration of dissolved oxygen in the broth must be 15% of
      saturation. Fed-batch strategies for high-cell-density cultivation were proposed.
      Pulse feed followed by constant feed produced a cell concentration of 32 g/L in
      18 h of fermentation and low PHAMCL content. Constant feed produced a cell
      concentration of 35 g/L, obtained in 27 h of fermentation, with up to 15% PHAMCL.
      Exponential feed produced a cell concentration of 30 g/L in 20 h of fermentation
      and low PHAMCL content. Using the last strategy, 21% PHAMCL was produced during a
      period of 34 h of fed-batch operation, with a final cell concentration of 40 g/L
      and NH4+ limitation. Using phosphate limitation, 50 g/L cell concentration, 63%
      PHAMCL and a productivity of 0.8 g/(L x h) were obtained in 42 h of fed-batch
      operation. The PHAMCL yield factors from consumed carbohydrate for N-limited and
      P-limited experiments were, respectively, 0.15 and 0.19 g/g.

PMID- 15496729
TI  - Production of optically pure D-lactic acid by Nannochlorum sp. 26A4.
AB  - Microalgae were screened from seawater for greenhouse gas CO2 fixation and D
      lactic acid production by self-fermentation and tested for their growth rate,
      starch content, and conversion rate from starch into D-lactic acid. More than 300
      strains were isolated, and some of them were found to have suitable properties
      for this purpose. One of the best strains, Nannochlorum sp. 26A4, which was
      isolated from Sakito Island, had a starch content of 40% (dry weight), and a
      conversion rate from consumed starch into D-lactic acid of 70% in the dark under
      anaerobic conditions. The produced D-lactic acid showed a high optical purity
      compared with the conventional one. The proposed new D-lactic acid production
      system using Nannochlorum sp. 26A4 should also be an effective technology for
      greenhouse gas CO2 fixation and/or conversion into industrial raw materials.

PMID- 15496730
TI  - Effect of ion and surfactant choice on the recovery of a histidine-tagged protein
      from tobacco extract using foam fractionation.
AB  - Tobacco plants can be used for the production of proteins for pharmaceutical
      applications. One of the most difficult and expensive tasks associated with this
      technology is isolating the product of interest from the hundreds of other
      chemicals found in tobacco. We describe a new recovery strategy in which the
      protein of interest is "tagged" with a histidine structure, which forms a complex
      with metal ions and a surfactant that will accumulate in the foamate of a foam
      fractionation step. His-gus, a histidine-tagged enzyme, was selectively recovered
      in the presence of two different surfactants and two different metal ions. The
      foam fractionation with N-epsilon-dodecylamido-N-alpha, N-alpha,
      bis(carboxymethyl)-L-lysine surfactant and Ni2+ ions resulted in an average His
      gus activity recovery value of 88% and an activity enrichment of 2.27. The
      performance of the recovery strategy without tobacco extract resulted in an
      average activity recovery value of 63.32% and an average activity enrichment
      value of 5.16, utilizing lauroyl ethylenediaminetriacetate surfactant and Ni2+
      ions. It was shown that even though a majority of the native tobacco proteins are
      removed during the prefoaming step, the presence of tobacco extract does affect
      the recovery of His-gus.

PMID- 15496732
TI  - CCD-based X-ray area detector for time-resolved diffraction experiments.
AB  - A fast X-ray area detector for diffraction, scattering and imaging experiments at
      microsecond to millisecond time resolution has been developed. The key element of
      the detector is a fast (291 frames s(-1)) framing camera with three CCDs. A prism
      forms identical images on the CCDs and the frame rate is increased three times by
      reading them alternately. In order to convert X-rays into visible light that is
      detectable with the CCDs, an X-ray image intensifier is used. The camera can also
      be used with a high-resolution X-ray detector. In both cases it was found to be
      important to use a phosphor with a short decay time to fully make use of the high
      speed framing capability of the camera. Preliminary results of a fibre
      diffraction experiment on a skeletal muscle and coronary angiography are
      presented.

PMID- 15496731
TI  - Suite of three protein crystallography beamlines with single superconducting bend
      magnet as the source.
AB  - At the Advanced Light Source, three protein crystallography beamlines have been
      built that use as a source one of the three 6 T single-pole superconducting
      bending magnets (superbends) that were recently installed in the ring. The use of
      such single-pole superconducting bend magnets enables the development of a hard X
      ray program on a relatively low-energy 1.9 GeV ring without taking up insertion
      device straight sections. The source is of relatively low power but, owing to the
      small electron beam emittance, it has high brightness. X-ray optics are required
      to preserve the brightness and to match the illumination requirements for protein
      crystallography. This was achieved by means of a collimating premirror bent to a
      plane parabola, a double-crystal monochromator followed by a toroidal mirror that
      focuses in the horizontal direction with a 2:1 demagnification. This optical
      arrangement partially balances aberrations from the collimating and toroidal
      mirrors such that a tight focused spot size is achieved. The optical properties
      of the beamline are an excellent match to those required by the small protein
      crystals that are typically measured. The design and performance of these new
      beamlines are described.

PMID- 15496733
TI  - Radiation damage to a protein solution, detected by synchrotron X-ray small-angle
      scattering: dose-related considerations and suppression by cryoprotectants.
AB  - In small-angle X-ray scattering experiments at high-brilliant synchrotron
      sources, protein aggregation results from radiation damage. The radiation-induced
      aggregation of lysozyme in solution was qualitatively evaluated based on forward
      scattering and radii of gyration. The scattering did not change below 400 Gy and
      increased exponentially above this dose. The aggregation is only seen beyond the
      critical dose rate, and the 'dilution effect' known in radiology was also
      observed. Mass spectroscopy of the lysozyme solution exposed to a monochromatic X
      ray beam did not show any cleavage of the polypeptide chain. Small-angle X-ray
      scattering patterns suggested that the radiation-induced aggregation should be a
      non-specific association of intact lysozyme, without substantial alterations of
      the folding topologies. It was found that the addition of small amounts of
      cryoprotectants, such as glycerol, ethylene glycol and sucrose, effectively
      reduced the radiation damage. Glycerol and ethylene glycol were identically
      effective in the 100 mM concentration range. A similar effective concentration
      was observed for sucrose. The damage reduction by the cryoprotectants was mainly
      ascribed to changes in the protein-protein interactions, and rarely to decreases
      in the diffusion rates of activated species.

PMID- 15496734
TI  - Hysteresis effect in FePd magnetic stripes studied by coherent soft X-ray
      resonant magnetic scattering.
AB  - An FePd thin film sample, showing magnetic stripe domains as imaged by magnetic
      force microscopy, has been measured by soft X-ray resonant magnetic scattering in
      reflection geometry. Illumination with coherent radiation, produced by inserting
      a 20 microm pinhole in front of the sample, leads to a magnetic speckle pattern
      in the scattered intensity that gives access to the domain morphology.
      Application of an in-plane magnetic field for a few seconds gives a strong change
      in the observed intensity fluctuations, which indicates a large degree of
      variation between the two patterns taken before and after field exposure. From
      the speckle pattern we calculate a degree of coherence of beta = 0.5 for the
      incident beam.

PMID- 15496735
TI  - The partial Talbot effect and its use in measuring the coherence of synchrotron X
      rays.
AB  - The Talbot effect is the self-imaging, at distances D multiple of D(R), of the
      intensity downstream of a periodic object. Earlier work with hard synchrotron
      radiation X-rays showed the variation with D of the fundamental Fourier component
      of intensity to be a good measurement of beam coherence. Any higher-order Fourier
      coefficients I (D, m > 1) would be periodic with a reduced period D(Rm) = D(R)/m
      for an ideally coherent incident beam (partial Talbot effect). The degree of
      coherence gamma(x) is sampled through the ratio of I (D, m) at D = 0 and
      multiples of D(Rm). This requires the Fourier coefficient for D = 0, which is not
      accessible for a phase object (no contrast at D = 0). However, the ratio of the
      slopes of I (D, m) at D = 0 and D = pD(Rm) also provides this information.
      Furthermore, a characterization of gamma(x) is possible, provided an assumption
      is made on its shape, using only the ratio of the Fourier coefficient I (D, m) of
      two images a distance pD(Rm) apart. Experiments with one- and two-dimensional
      phase gratings and a mixed (amplitude and phase) two-dimensional grating confirm
      that the partial Talbot effect approach is viable. It requires a reduced range of
      distances, and yields important results directly, obviating the need for computer
      fits. In particular, 8% of the beam intensity was found to have very low
      coherence in the vertical direction, probably due to monochromator imperfection.

PMID- 15496736
TI  - Experimental requirements for light-induced reactions in powders investigated by
      time-resolved X-ray diffraction.
AB  - A general outline of how to perform a light-excited time-resolved diffraction
      experiment by applying the optical pump/X-ray probe technique is given. Owing to
      the difference in penetration depths between the optical light (laser) pump and
      the X-ray probe, only specific or specially designed crystalline systems can be
      investigated, so special requirements have to be fulfilled concerning the sample
      and its compartments. A summary of the experimental conditions of optical pump/X
      ray probe experiments is presented, emphasizing why the use of powder diffraction
      is a useful and necessary X-ray technique for this kind of experiment. The
      possibilities and bottlenecks of time-resolved X-ray diffraction on the
      picosecond time scale will be demonstrated in the powder diffraction studies of
      N,N-dimethylaminobenzonitrile and N,N-diisopropylaminobenzonitrile, where the
      photo-induced structural changes of these molecular organic systems have been
      studied as a function of time.

PMID- 15496737
TI  - Synergistic use of synchrotron radiation techniques for biological samples in
      solution: a case study on protein-ligand recognition by the peroxisomal import
      receptor Pex5p.
AB  - Circular dichroism spectropolarimetry and X-ray scattering data, obtained using
      synchrotron radiation, can yield information about the secondary and tertiary
      structure of proteins in solution. These techniques have been used to analyse the
      architecture and shape of a complex of two proteins in solution. The crystal
      structures of two separate proteins, the C-terminal domain of Pex5p and SCP2, are
      available but their complex has not previously been structurally characterized.
      Circular dichroism spectropolarimetry indicated that complex formation requires
      little secondary structure rearrangement. X-ray scattering data fit an elongated
      irregular 'shoe'-shaped particle of the complex of the two proteins, with
      dimensions of the order of 30 A x 40 A x 90 A. Comparison with the known crystal
      structures suggests that this 'shoe' shape requires a conformational change of
      the C-terminus of SCP2 to appropriately locate its peroxisomal targeting signal
      type-1 recognition motif into the binding pocket of the Pex5p receptor.
      Implications of the combined use of synchrotron-based circular dichroism
      spectropolarimetry and X-ray scattering in structural biology and proteomics are
      discussed.

PMID- 15496738
TI  - X-ray absorption spectroscopy study of the LixFePO4 cathode during cycling using
      a novel electrochemical in situ reaction cell.
AB  - The extraction and insertion of lithium in LiFePO4 has been investigated in
      practical Li-ion intercalation electrodes for Li-ion batteries using Fe K-edge X
      ray absorption spectroscopy (XAS). A versatile electrochemical in situ reaction
      cell was utilized, specifically designed for long-term X-ray experiments on
      battery electrodes during the lithium-extraction/insertion process in electrode
      materials for Li-ion batteries. The electrode contained about 7.7 mg of LiFePO4
      on a 20 microm-thick Al foil. In order to determine the charge compensation
      mechanism and structural perturbations occurring in the system during cycling, in
      situ X-ray absorption fine-structure spectroscopy (XAFS) measurements were
      conducted on the cell at a moderate rate using typical Li-ion battery operating
      voltages (3.0-4.1 V versus Li/Li+). XAS studies of the LiFePO4 electrode measured
      at the initial state (LiFePO4) showed iron to be in the Fe(II) state
      corresponding to the initial state (0.0 mAh) of the battery, whereas in the
      delithiated state (FePO4) iron was found to be in the Fe(III) state corresponding
      to the final charged state (3 mAh) of the battery. The X-ray absorption near-edge
      structure (XANES) region of the XAS spectra revealed a high-spin configuration
      for the two states [Fe(II), d6 and Fe(III), d5]. The XAFS data analysis confirmed
      that the olivine structure of the LiFePO4 and FePO4 is retained by the
      electrodes, which is in agreement with the X-ray diffraction observations on
      these compounds. The XAFS data that were collected continuously during cycling
      revealed details about the response of the cathode to Li insertion and
      extraction. These measurements on the LiFePO4 cathode show that the material
      retains good structural short-range order leading to superior cycling.

PMID- 15496739
TI  - Small-angle X-ray scattering on the ChemMatCARS beamline at the Advanced Photon
      Source: a study of shear-induced crystallization in polypropylene.
AB  - The first ever time-resolved small-angle X-ray scattering (SAXS) data from the
      undulator 15-ID-D beamline (ChemMatCARS) are presented. A 1.3 A (9.54 keV) X-ray
      beam was selected to study the structure development in a polypropylene sample
      during shear-induced crystallization. A Linkam CSS450 shear cell provided the
      temperature and shear control. The polypropylene was first melted and then
      quenched to the crystallization temperature, where a step shear was applied. The
      SAXS data were collected using a Bruker 6000 CCD detector, which provided images
      of excellent resolution. The SAXS images (with 180 degrees rotational symmetry)
      indicated that the polypropylene crystallizes with a high degree of anisotropy,
      and the lamellae are oriented perpendicular to the flow direction.

PMID- 15496740
TI  - Comments on treatment of EXAFS data taken in the fluorescence mode in non-linear
      conditions by G. Ciatto et al. (2004). J. Synchrotron Rad. 11, 278-283.

PMID- 15496743
TI  - Measuring higher education outcomes with a multidimensional Rasch model.
AB  - A multidimensional Rasch model was applied to two instruments measuring abilities
      in two related areas of a university general education curriculum. Grades from
      related courses were also calibrated using the Rasch model. Thus, course grades,
      test items, and persons were all placed on the same metric. Incorporating grades
      within the metric provided additional meaning to the measures; instructors could
      see which items were matched to students in a particular grade range for a
      course. This could help not only in interpreting items but also in interpreting
      grades. Test items and grades fit the model reasonably well, with adequate person
      separation reliability.

PMID- 15496744
TI  - Measurement in clinical vs. biological medicine: the Rasch model as a bridge on a
      widening gap.
AB  - In the dominant Bio-medical paradigm Medicine is mostly Biology applied to Man.
      Measurement in Biology stems from physical sciences and has established validity.
      This is not the case for whole-person variables such as behaviors and psychic
      conditions (disability, pain, knowledges). The very existence of these variables
      can only be inferred by observing samples of representative behaviors. The
      quantity of the inferred variable may only come from subjective and discrete
      counts (scores) of events (coming in a questionnaire). Contemporary statistics
      demonstrated that raw scores intrinsically lack fundamental properties for
      scientific measurement, whatever their algebraic manipulations. This adds to the
      stigmatization of Clinical Medicine as "soft science", compared to Bio-medicine.
      In the 1960s Georg Rasch inaugurated a new statistical approach allowing
      transformation of raw scores into objective linear measures comparable to
      physical measures. This may help the Bio-medical paradigm to redirect resources
      from laboratory bench back to bedside.

PMID- 15496745
TI  - Dimensionality and construct validity of an instrument designed to measure the
      metacognitive orientation of science classroom learning environments.
AB  - The purpose of this study was to establish the factorial construct validity and
      dimensionality of the Metacognitive Orientation Learning Environment Scale
      Science (MOLES-S) which was designed to measure the metacognitive orientation of
      science classroom learning environments. The metacognitive orientation of a
      science classroom learning environment is the extent to which psychosocial
      conditions that are known to enhance students' metacognition are evident within
      that classroom. The development of items comprising this scale was based on a
      theoretical understanding of metacognition, learning environments and the
      development of previous learning environments instruments. Four possible
      hypothesized structure models, each consistent with the literature, were reviewed
      and their merits were compared on the basis of empirical data drawn from two
      populations of 1026 and 1223 Hong Kong secondary school students using
      confirmatory factor analysis procedures. The scale was calibrated using the Rasch
      rating scale model using data from the 1223 student sample. The results suggest
      that there is strong evidence to support the factorial construct validity of the
      MOLES-S but that, on the basis of the Rasch analysis, there are still suggestions
      for further refinement and improvement of the MOLES-S.

PMID- 15496746
TI  - A new class of parametric IRT models for dichotomous item scores.
AB  - A new class of parametric IRT models for dichotomously scored items is presented.
      The new class of models is a subclass of both the class of models defined by the
      four-parameter logistic item response function and the nonparametric Double
      Monotonicity (DM) model. Three special cases of this new class of models are
      discussed. One of these special cases is shown to be the one-parameter logistic
      Rasch model. Both specific objectivity at the interval level of measurement and
      the sufficiency of the total score for the latent trait are shown to be
      measurement properties of the whole new class of models. For maximum likelihood
      estimation of the model parameters, both a joint and a conditional likelihood
      function are proposed.

PMID- 15496747
TI  - Comparing factor analysis and the Rasch model for ordered response categories: an
      investigation of the scale of gambling choices.
AB  - Using both factor analysis (Spearman, 1904) and the Rasch model for ordered
      response categories (Andrich, 1978), the present study investigated the structure
      of the Scale of Gambling Choices (SGC, Baron, Dickerson and Blaszczynski, 1995).
      The scale was administered to a participant sample (n = 210) consisting of 57
      first year psychology students, 104 in situ club Electronic Gaming Machine (EGM)
      players and 49 self-referred problem gamblers. It was hypothesised that the
      results yielded by factor analysis and Andrich's model would not agree with
      respect to the behaviour of individual items. This hypothesis was supported;
      supporting the results of previous research (Johnson, et al., 1995; Raju, et al.,
      2002; Reise, et al., 1993). It was also hypothesised that a relationship would
      exist between item factor loadings and item expected value curve slope
      coefficients. This hypothesis was not supported and so hence did not support the
      findings of Parsons and Hulin (1982) and Roskam (1985). It was concluded that
      this was perhaps due to the different latent variable conceptions which exist
      between the Rasch models and factor analysis (Bollen, 2002). The limitations of
      the research were outlined and suggestions for future research were made.

PMID- 15496748
TI  - Assessing the assumption of symmetric proximity measures in the context of
      multidimensional scaling.
AB  - Applications of multidimensional scaling often make the assumption of symmetry
      for the population matrix of proximity measures. Although the likelihood of such
      an assumption holding true varies from one area of research to another, formal
      assessment of such an assumption has received little attention. The present
      article develops a nonparametric procedure that can be used in a confirmatory
      fashion or in an exploratory fashion in order to probabilistically assess the
      assumption of population symmetry for proximity measures in a multidimensional
      scaling context. The proposed procedure makes use of the bootstrap technique and
      alleviates the assumptions of parametric statistical procedures. Computer code
      for R and S-Plus is included in an appendix in order to carry out the proposed
      procedures.

PMID- 15496749
TI  - Detecting item bias with the Rasch model.
AB  - The purpose of this article is to introduce the concept of item bias,
      highlighting the differences between the definition of the term as it is used
      within Rasch measurement and the definition of the term as it is used in the true
      score model, non-model based approaches, or multi-item parameter latent trait
      models. The discussion continues with a description of alternative methods of
      assessing item bias within the Rasch measurement framework and discusses the
      power of these methods to detect the presence of item bias. The discussion
      concludes with several examples drawn from a number of different mathematics
      tests. This includes a comparison of the Rasch separate calibration t-test and
      the Mantel-Haenszel approaches.

PMID- 15496766
TI  - Genetics.

PMID- 15496767
TI  - Environmental influences on asthma and allergy.

PMID- 15496768
TI  - Early immunological influences.

PMID- 15496769
TI  - Prediction and early diagnosis.

PMID- 15496770
TI  - Preventive measures section 1: early interventions.

PMID- 15496772
TI  - Allergy and asthma education.

PMID- 15496771
TI  - Preventive measures section 2: occupational allergies and asthma.

PMID- 15496773
TI  - The costs of allergy and asthma and the potential benefit of prevention
      strategies.

PMID- 15496774
TI  - Fundamentals of endotoxin structure and function.

PMID- 15496775
TI  - Bacterial exotoxins.

PMID- 15496776
TI  - Capsular polysaccharides and their role in virulence.

PMID- 15496777
TI  - Fimbriae, pili, flagella and bacterial virulence.

PMID- 15496778
TI  - Gram-positive adhesins.

PMID- 15496779
TI  - Microbial pathogenesis and biofilm development.

PMID- 15496780
TI  - Bacterial peptidases.

PMID- 15496781
TI  - Bacterial invasins: molecular systems dedicated to the invasion of host tissues.

PMID- 15496783
TI  - Pathogenicity islands and their role in bacterial virulence and survival.

PMID- 15496782
TI  - Bacterial iron transport related to virulence.

PMID- 15496784
TI  - Horizontal and vertical gene transfer: the life history of pathogens.

PMID- 15496785
TI  - The history and rationale of daily and nightly hemodialysis.

PMID- 15496786
TI  - Requirements of an in-center daily hemodialysis program.

PMID- 15496787
TI  - Technical requirements of a home hemodialysis program.

PMID- 15496788
TI  - Patient recruitment and selection.

PMID- 15496789
TI  - Patient training and education.

PMID- 15496790
TI  - Vascular access.

PMID- 15496791
TI  - Cardiovascular risk factor modification with quotidian hemodialysis.

PMID- 15496792
TI  - Calcium and phosphorus control.

PMID- 15496793
TI  - Management of anemia.

PMID- 15496794
TI  - Dialysis prescription and dose monitoring in frequent hemodialysis.

PMID- 15496795
TI  - Nutrition.

PMID- 15496796
TI  - Quality of life.

PMID- 15496797
TI  - A business model approach to quotidian hemodialysis.

PMID- 15496798
TI  - Patient testimonials--'back in the land of the living'. As told by quotidian
      hemodialysis patients.

PMID- 15496799
TI  - Genetic variation: nutritional implications.

PMID- 15496800
TI  - Gene: environment interactions and coronary heart disease risk.

PMID- 15496801
TI  - Genes, diet and plasma lipids: the evidence from observational studies.

PMID- 15496802
TI  - Dynamic relationships between the genome and exposures to environments as causes
      of common human diseases.

PMID- 15496803
TI  - Achieving balance in the omega-6/omega-3 ratio through nutrigenomics.

PMID- 15496804
TI  - Nutrients and gene expression.

PMID- 15496805
TI  - Nutrigenomics in efficacy and safety evaluation of food components.

PMID- 15496806
TI  - Genetic variation and nutritional requirements.

PMID- 15496807
TI  - Vitamin metabolism, genetics and the environment.

PMID- 15496808
TI  - Gene-nutrient interactions in type 1 diabetes.

PMID- 15496809
TI  - Cancer nutrigenomics.

PMID- 15496810
TI  - Genetic variation and physical performance.

PMID- 15496811
TI  - Making sense of the Canadian experience. Notes from the Editor-in-Chief.

PMID- 15496812
TI  - Regionalization: making sense of the Canadian experience.
AB  - This paper revisits the purposes and achievements of regionalization, a decade
      after its widespread implementation across Canada, and considers to what extent
      changes in healthcare concepts, emphasis and delivery can reasonably be
      attributed to it. The authors address four main questions. What, conceptually, is
      regionalization in healthcare, and what distinguishes it as a structure? How was
      regionalization intended to contribute to the achievement of the goals for the
      health system articulated in the 1980s and 1990s? How has regionalization been
      implemented in Canada, and how have these factors affected its potential to
      achieve its intended impact? And finally, with the experience gained over the
      last decade, how might we now (re)design regionalization to better contribute to
      health system goals? In Canada, regionalization of healthcare has entailed more
      than devolution and decentralization of services from provincial governments to
      regional authorities. It included consolidation of authority from local boards
      and agencies, and some centralization of services. Regionalization was the remedy
      proposed for the diagnosis of fragmentation and incoherence made by commissions
      across the country in the 1980s. Regionalization addressed the organizational
      dimensions of the perceived problems, but provincial governments added goals
      unrelated to structural change to its mandate. The authors assess the potential
      impact of regionalization on health system goals and take stock of current
      Canadian circumstances. Even where regionalization's impact is theoretically
      high, there are many practical limits to its effect. Although it can facilitate
      or impede change, in the end the will and actions of provincial governments,
      providers and other actors in the health system are fundamental to attaining more
      substantive goals. Many health reform goals require nothing less than a
      transformation of how society views health, and in the culture of healthcare
      delivery. Further, the authors argue that the implementation of regionalization
      in Canada has been limited. Devolution has typically been halting and
      provisional; there has been little stability; and there have been constraints on
      the ability to act. These limitations have reduced its potential effect. The
      authors conclude with proposals for increasing regionalization's contribution to
      health reform goals. These include a more stable and transparent provincial-RHA
      relationship, information and measures to better align resources to needs,
      increased regional-level system integration and changes to organizational culture
      and practice in the health system.

PMID- 15496813
TI  - Regionalization and the allocation of healthcare resources to meet population
      health needs.
AB  - This brief commentary examines why regionalization can improve the extent to
      which resources are allocated in line with need; highlights the challenges
      associated with the two stages of resource allocation within regionalized systems
      (allocation from the ministry to the regions and allocation within a region); and
      assesses the experience with needs-based funding in Canada under regionalized
      governance.

PMID- 15496814
TI  - Regionalization in Canada: a promising heritage to build on.
AB  - Regionalization has been a major policy experiment in Canadian healthcare.
      Objectives attached to this policy were ambitious and somewhat unrealistic.
      Regional health authorities have shown that they can play a useful role in
      implementing healthcare reform. However, their legitimacy is difficult to
      sustain, and they need to renew their roles in order to remain a valuable asset
      in the improvement of healthcare delivery. A model of leadership for RHAs based
      on content and process dimensions is proposed to support the development of their
      role in improving the delivery of care. RHAs need to depart from a too distant
      mode of managing healthcare and support more healthcare organizations in their
      search for innovative ideas and organizing models and strategies. By adopting
      such an approach to their roles, it is expected that RHAs will further contribute
      to the improvement of healthcare and consequently will gain legitimacy to develop
      more autonomous policies with regard to broad ideals such as democratization and
      health improvement.

PMID- 15496815
TI  - Regionalization: an opportunity for improving management.
AB  - Lewis and Kouri provide an excellent review of the status of regionalization
      across Canada. Their paper examines the potential benefits of regionalization and
      the factors increasing or decreasing potential impact, the state of
      regionalization in each province and regionalization's contribution to health
      reforms. Of the six goals mentioned in the potential benefits of regionalization,
      four focus on effectiveness and efficiency and two on accountability and public
      input. The political nature of healthcare is mentioned often, and the negative
      impact of end-runs to political authority if patients or providers are not
      satisfied is underlined.

PMID- 15496816
TI  - Let regionalization continue to evolve.
AB  - This commentary provides a practical perspective on the benefits of
      regionalization within the context of the lead paper by Lewis and Kouri.
      Discussion of the best structure of health systems needs to take into account the
      reality that constitutional and funding responsibility--and therefore
      accountability--for our healthcare system lies with provincial governments.
      Accountability at the provincial government level is simply a part of
      regionalization and should be expected by health system managers. Regionalization
      of healthcare is in its infancy. Systems necessary to support regionalization,
      which can only be established under a regionalized structure (e.g., information
      technology, procurement, human resources and service planning), are evolving.
      Given the size and complexity of the healthcare system, as we gain more
      experience with regionalization the systems we need to support it will attain
      their potential, as will the managers of the system. Regionalization was the most
      appropriate option for healthcare in the 1990s given the objectives of provincial
      governments to achieve efficiencies, better utilize resources and improve patient
      care. We must allow regionalization to evolve in order to see long-term
      improvements in the healthcare system.

PMID- 15496817
TI  - Continuum of care must be under region's control.
AB  - Lewis and Kouri have provided an overview of the various aspects of
      regionalization, its implementation and resulting impact across Canada. The
      authors note that although it has had some success in Canada, it remains unclear
      as to what the single compelling vision or focus is or should be. This commentary
      suggests that the inability to include all components of the continuum of care
      within most models accounts for the lack of "transformational change" that
      regionalization has as yet been unable to achieve. To expect that any significant
      gains will be made in the regionalization process until all aspects of the
      continuum are under a region's control is unrealistic. The commentary proposes
      that it is time to review the underlying premises for regionalization and its
      current emphasis on acute care.

PMID- 15496818
TI  - Critical insights for researchers and decision-makers.
AB  - Regionalization organizations are essential building blocks of health
      restructuring and are designed to be agents of change and integration in most
      provinces in Canada. Yet, despite this, most citizens seem to be unaware of
      regional health authorities, why they exist, the drivers and constraints
      involved, or whether these divergent structures and regional governance processes
      have influenced patterns of restructuring and health outcomes. And even when
      discussions have taken place, these debates have tended to be more prescriptive
      than analytical. All of this has complicated the task of conceptualizing and
      making sense of the determinants that have influenced regionalization forms of
      health service restructuring in Canada and how these have influenced the way
      resources have been allocated, decisions reached and accountability exercised.

PMID- 15496819
TI  - Devolution--a solution for Ontario: could the lone wolf lead the pack?
AB  - In response to what we describe as the "accountability gap" in healthcare, nine
      provinces have embraced the devolution of management responsibility and authority
      from central government administrations to regional health authorities. Ontario,
      Canada's most populous province, is the lone wolf. This commentary focuses on the
      consequences of Ontario's reluctance to adopt devolution. The authors argue that
      devolution is an important first step in improving the lines of accountability
      within publicly funded healthcare; however, as a reform initiative, devolution
      must form part of a series of interlocking initiatives. These complementary
      reforms include refocusing the debate from funding (money) to governance,
      clarifying the governance roles of both the federal and provincial governments
      and developing an incentive- and information-based system that is geared more to
      rewarding gains in healthcare outcomes as opposed to the delivery of health
      services. With a new government in Ontario, there is now a window of opportunity
      to capitalize on the experiences and failures of other provinces and for Ontario
      to emerge as the leader of the pack, rather than the lone wolf.

PMID- 15496820
TI  - Reconstructing cancer services in Ontario.
AB  - This paper draws upon experience gained in the recent restructuring of cancer
      services in Ontario that can provide insights for broader regionalization
      efforts. Although Ontario is the only province in Canada not to regionalize its
      healthcare system, the Ontario cancer services system, like most others in
      Canada, is based on a regionalized system. However, the growing burden of cancer
      and predictable crises in cancer services in Ontario necessitated a rethinking of
      how the cancer system should be structured and how services should be delivered.
      Based on recommendations by the Cancer Services Implementation Committee in 2001,
      Ontario's cancer services system has recently gone through major restructuring,
      which has established new institutional arrangements for the Ministry of Health
      and Long-Term Care, Cancer Care Ontario (CCO) (the provincial cancer agency) , a
      new Quality Council and 11 new regionally based Integrated Cancer Programs
      (ICPs). This restructuring has created several levers for promoting regional
      change and motivating performance improvement, including (1) public reporting on
      performance with a new quality mandate, (2) fiscal and performance-based
      agreements between CCO and the ICPs, (3) leading and coordinating communities of
      practice and (4) direct ministerial access. While institutional relationships are
      still developing, these experiences may provide important insights for
      regionalization efforts in other jurisdictions and sectors in Canada.

PMID- 15496821
TI  - Regionalization: are even the flaws quintessentially Canadian?
AB  - Lewis and Kouri's analysis of the Canadian experience of regionalization
      resonates strongly with the Australian experience, but Australia lacks a clear
      trend. Rather, there is a record of oscillation in the system between
      consolidation "at state level" and devolution "to regions or networks", although
      there is a general movement away from atomization "that is, stand-alone hospitals
      and health services". This paper briefly reviews the Australian situation, and
      then focuses on the differences in our two countries' regionalization
      experiences. I argue that two Australian problems "the federal/state split and
      the struggle for control" have led to different outcomes, and they throw a
      different light on the basic question posed by Lewis and Kouri: How might
      regionalization better contribute to health system goals? This paper is written
      from the perspective of a participant in Australia's regionalization process-
      most recently as chair of the governance and funding task group of a
      comprehensive health system review in South Australia, one of Australia's eight
      states and territories. The task group recommendation to regionalize the system
      "Generational Health Review 2003" was accepted, and the changes come into force
      in July 2004. This looks like being the last devolution in the Australian system
      for some time.

PMID- 15496822
TI  - Regionalizing Canadian healthcare: the good--the bad--the ugly.
AB  - In their lead paper, Lewis and Kouri leave us with a revealing and perplexing
      picture of Canadian experience with healthcare regionalization. Take-home
      messages are that regionalization is riddled with dilemmas, saddled with problems
      and tasked to find solutions current incentives do not encourage. And yet this
      mode of restructuring healthcare endures through peaks and flows of reconfiguring
      and renaming exercises, rarely discarded completely and apparently making some
      positive differences. While this peer commentary shares many of the lead authors'
      perspectives, it suggests that if we want to better understand the role of
      regionalization as a structure supporting organizational change, then there is
      value in broadening some investigative spaces and some analytical frames when
      trying to understand this seemingly endless restructuring effort. The commentary
      begins by arguing that we should seek transferable lessons and lenses more widely
      and more often, as regionalization is neither uniquely Canadian nor solely
      healthcare oriented. The remainder of the paper revisits some of the Lewis and
      Kouri terrain, viewing in turn the good, the bad and the ugly aspects of
      regionalization and reflecting on how these characteristics influence change
      opportunities both in practice and for research.

PMID- 15496824
TI  - Self-reported frequent mental distress among adults--United States, 1993-2001.
AB  - Poor mental health is a major source of distress, disability, and social burden;
      in any given year, as many as one in five adults in the United States has a
      mental disorder. To identify differences among populations and factors
      contributing to poor mental health, CDC examined the prevalence of frequent
      mental distress (FMD) among U.S. adults by race/ethnicity, socioeconomic status
      (SES), and sex, by using aggregate data from Behavioral Risk Factor Surveillance
      System (BRFSS) surveys for 1993-2001. This report describes the results of that
      analysis, which indicated that the prevalence of FMD varied among racial/ethnic
      populations and increased substantially among whites and blacks. In addition, FMD
      was reported more frequently by women and by persons with low SES within each
      racial/ethnic population. Targeting adverse socioeconomic risk factors and
      improving access to mental health services might decrease FMD among adults and
      reduce racial/ethnic disparities in mental health.

PMID- 15496825
TI  - Transmission of primary and secondary syphilis by oral sex--Chicago, Illinois,
      1998-2002.
AB  - During 1998-2002, the STD/HIV Prevention and Care Program of the Chicago
      Department of Public Health (CDPH) recorded 1,582 cases of primary and secondary
      (P&S) syphilis, the most of any U.S. city. Although case numbers and overall
      rates remained stable in Chicago during this period, patterns of transmission
      changed substantially. Throughout most of the 1990s, P&S syphilis was reported
      almost exclusively among heterosexuals. During 1998-2000, however, men who have
      sex with men (MSM) accounted for approximately 15% of Chicago's P&S syphilis
      morbidity. Since 2001, MSM have accounted for nearly 60% of patients with P&S
      syphilis. During 2000-2002, CDPH conducted interviews with persons with syphilis;
      some MSM reported they had engaged in only oral sex and were surprised to have
      acquired syphilis. In response, CDPH began collecting information on oral sex
      from persons with syphilis. To assess the role of oral sex in the transmission of
      P&S syphilis in Chicago, CDPH analyzed surveillance data and interview responses.
      This report summarizes the results of these analyses, which suggested that a
      substantial proportion (13.7%) of syphilis cases were attributed to oral sex,
      particularly among MSM. Persons who are not in a long-term monogamous
      relationship and who engage in oral sex should use barrier protection (e.g., male
      condoms or other barrier methods) to reduce the risk for sexually transmitted
      disease (STD) transmission.

PMID- 15496826
TI  - Postexposure prophylaxis, isolation, and quarantine to control an import
      associated measles outbreak--Iowa, 2004.
AB  - On March 12, 2004, a college student infectious with measles returned to Iowa
      from India by a commercial airliner; the case was subsequently linked to two
      other measles cases. This report updates information about this outbreak and
      provides details regarding vaccination, quarantine, and other measures used by
      Iowa public health authorities to interrupt disease transmission in a vulnerable
      population. The effective uses of quarantine and isolation during the outbreak
      underscore the utility of these public health tools in halting communicable
      disease transmission.

PMID- 15496827
TI  - Fibronectin overexpression inhibits trabecular meshwork cell monolayer
      permeability.
AB  - PURPOSE: To study whether excess synthesis of an extracellular matrix (ECM)
      component, fibronectin (FN), underlying the monolayer of human trabecular
      meshwork (HTM) cells, influences permeability. METHODS: To upregulate FN
      expression, HTM cells were grown in high glucose (30 mM) medium for 10 days. In
      parallel, cells were grown in normal (5 mM) medium as control, and two separate
      groups of HTM cells were grown in high glucose medium for transfection with FN
      antisense phosphorothioate oligonucleotides (AS-FN oligos) to modulate high
      glucose induced FN overexpression, or random phosphorothioate oligonucleotides
      (Ran oligos) as control. FN protein expression and distribution was assessed by
      western blot analysis and immunofluorescence microscopy. In parallel, HTM cells
      were grown in transwell plates in normal or high glucose medium to perform in
      vitro permeability (IVP) assays and to assess transelectrical resistance (TER).
      RESULTS: Western blot analysis showed FN expression was upregulated by 27%
      (p=0.018) in HTM cells grown in high glucose medium compared to cells grown in
      normal medium. Immunofluorescence microscopy showed intense FN immunostaining,
      and IVP results showed a consistent reduction in monolayer permeability (13%
      reduction, p=0.004) in cells grown in high glucose medium compared to cells grown
      in normal medium. When cells grown in high glucose medium were transfected with
      AS-FN oligos FN expression was reduced by 33% (p=0.009) and resulted in increased
      permeability to near normal levels (98+/-7% of control, p=0.01), whereas random
      oligos had no effect on either FN expression or IVP. TER was significantly
      increased across TM cell monolayers grown in high glucose compared to those grown
      in normal medium (143+/-11% of control, p=0.001), which was reduced when cells
      were transfected with AS-FN oligos (109+/-7% of control, p=0.02) whereas cells
      transfected with random oligos showed no change. CONCLUSIONS: Excess FN synthesis
      by trabecular meshwork cells may contribute to blockage in aqueous outflow
      associated with the development of primary angle open glaucoma (POAG).

PMID- 15496828
TI  - Analysis of transcriptional regulation of the small leucine rich proteoglycans.
AB  - PURPOSE: Small leucine rich proteoglycans (SLRPs) constitute a family of secreted
      proteoglycans that are important for collagen fibrillogenesis, cellular growth,
      differentiation, and migration. Ten of the 13 known members of the SLRP gene
      family are arranged in tandem clusters on human chromosomes 1, 9, and 12. Their
      syntenic equivalents are on mouse chromosomes 1, 13, and 10, and rat chromosomes
      13, 17, and 7. The purpose of this study was to determine whether there is
      evidence for control elements, which could regulate the expression of these
      clusters coordinately. METHODS: Promoters were identified using a comparative
      genomics approach and Genomatix software tools. For each gene a set of human,
      mouse, and rat orthologous promoters was extracted from genomic sequences.
      Transcription factor (TF) binding site analysis combined with a literature search
      was performed using MatInspector and Genomatix' BiblioSphere. Inspection for the
      presence of interspecies conserved scaffold/matrix attachment regions (S/MARs)
      was performed using ElDorado annotation lists. DNAseI hypersensitivity assay,
      chromatin immunoprecipitation (ChIP), and transient transfection experiments were
      used to validate the results from bioinformatics analysis. RESULTS: Transcription
      factor binding site analysis combined with a literature search revealed co
      citations between several SLRPs and TFs Runx2 and IRF1, indicating that these TFs
      have potential roles in transcriptional regulation of the SLRP family members. We
      therefore inspected all of the SLRP promoter sets for matches to IRF factors and
      Runx factors. Positionally conserved binding sites for the Runt domain TFs were
      detected in the proximal promoters of chondroadherin (CHAD) and osteomodulin
      (OMD) genes. Two significant models (two or more transcription factor binding
      sites arranged in a defined order and orientation within a defined distance
      range) were derived from these initial promoter sets, the HOX-Runx (homeodomain
      Runt domain), and the ETS-FKHD-STAT (erythroblast transformation specific
      forkhead-signal transducers and activators of transcription) models. These models
      were used to scan the genomic sequences of all 13 SLRP genes. The HOX-Runx model
      was found within the proximal promoter, exon 1, or intron 1 sequences of 11 of
      the 13 SLRP genes. The ETS-FKHD-STAT model was found in only 5 of these genes.
      Transient transfections of MG-63 cells and bovine corneal keratocytes with Runx2
      isoforms confirmed the relevance of these TFs to expression of several SLRP
      genes. Distribution of the HOX-Runx and ETS-FKHD-STAT models within 200 kb of
      genomic sequence on human chromosome 9 and 500 kb sequence on chromosome 12 also
      were analyzed. Two regions with 3 HOX-Runx matches within a 1,000 bp window were
      identified on human chromosome 9; one located between OMD and osteoglycin
      (OGN)/mimecan genes, and the second located upstream of the putative
      extracellular matrix protein 2 (ECM2) promoter. The intergenic region between OMD
      and mimecan was shown to coincide with different patterns of DNAse I
      hypersensitivity sites in MG-63 and U937 cells. ChiP analysis revealed that this
      region binds Runx2 in U937 cells (mimecan transcript note detectable), but binds
      Pitx3 in MG-63 cells (expressing high level of mimecan), thereby demonstrating
      its functional association with mimecan expression. Upon comparing the
      predictions of S/MARs on the relevant chromosomal context of human chromosomes 9
      and 12 and their rodent equivalents, no convincing evidence was found that the
      tandemly arranged genes build a chromosomal loop. CONCLUSIONS: Twelve of 13 known
      SLRP genes have at least one HOX-Runx module match in their promoter, exon 1,
      intron 1, or intergenic region. Although these genes are located in different
      clusters on different chromosomes, the common HOX-Runx module could be the basis
      for co-regulated expression.

PMID- 15496829
TI  - Novel retinal genes discovered by mining the mouse embryonic RetinalExpress
      database.
AB  - PURPOSE: Bioinformatics has emerged as a powerful tool for identifying novel
      genes and pathways associated with retinal biology and disease. The developing
      mouse retina expresses an exceedingly large and complex variety of genes. Many of
      these genes have not been characterized but nevertheless are likely to have
      important developmental or physiological functions. The purpose of this study was
      to use an in silico approach with a mouse embryonic retinal database of
      cDNAs/expressed sequence tags (ESTs) named RetinalExpress to identify previously
      uncharacterized genes that are represented in the developing retina. METHODS:
      cDNA clones unique to the RetinalExpress database were identified by comparing
      clones in the RetinalExpress database with those in other cDNA/EST databases. We
      used a hierarchical filtering procedure with high stringency criteria that
      included sequence quality, colinearity with hypothetical gene sequences, and
      absence of any substantial existing annotation to select clones that were likely
      to represent novel genes. Selected clones were located on mouse chromosomes using
      National Center for Biotechnology Informatics Map Viewer software and the
      database from the University of California at Santa Cruz Genome Bioinformatics
      Web browser. The expression of selected retinal transcripts was determined using
      reverse transcriptase (RT)-PCR. In situ hybridization of sectioned embryonic and
      postnatal retinas was performed to determine spatial expression patterns of
      selected transcripts. RESULTS: Of the 27,765 cDNA clones from RetinalExpress that
      we filtered through several public cDNA/EST databases, 26 cDNA/EST sequences were
      identified that, at the time of the analysis, were unique to RetinalExpress.
      Seventeen clones were selected for RT-PCR analysis, and retinal transcripts
      corresponding to previously uncharacterized genes were unambiguously detected for
      six clones. Three genes encoded open reading frames containing putative
      functional domains; one sequence contained an HMG DNA binding domain, another, an
      RFX DNA binding domain, and another, a phospholipase C catalytic domain X.
      Transcripts from the genes encoding DNA binding domains were expressed in
      embryonic and postnatal retinas with distinct spatial patterns. CONCLUSIONS: The
      characterization of 26 mouse genes whose partial nucleotide sequences were
      uniquely represented in the RetinalExpress cDNA/EST database demonstrated the
      feasibility of retinal gene discovery using in silico analysis. Two of these
      genes had distinctive spatial expression patterns in the retina and one was
      likely to function as a DNA binding protein in embryonic and postnatal retinas.
      The gene identification approach described here demonstrates the usefulness of
      establishing large cDNA/EST databases from highly specialized neuronal tissues
      such as the retina to find novel genes.

PMID- 15496830
TI  - [Epidemiology and a course of allergic rhinitis in children].
AB  - The authors present the results of a clinico-epidemiological trial of allergic
      rhinitis (AR) in children according to the ISAAC program (International Study of
      Asthma and Allergy in Childhood). AR symptoms occurred in 12.1+/-0.8% children
      including in 9.7+/-1.1% first-formers and 14.5+/-1.3% eight-formers. AR is
      represented by mild (49.4%), moderate (31.4%) and severe (19.2%) forms.
      Prevalence of AR in children by active diagnosis is 4.7 times higher than by
      reference and reaches 9.8+/-0.7%. Six-year follow-up shows that 59.6% children
      developed bronchial asthma, more frequently boys aged 3-7 years. Progression of
      AR occurred in 25.5% children while a favourable course of the disease with a
      complete clinical remission was observed in 14.9%.

PMID- 15496831
TI  - [Late effects of long-term exposure to low-dose ionizing radiation on lymphoid
      pharyngeal system in children].
AB  - The examination of 468 children and adolescents estimated frequency and structure
      of chronic pathology of the pharyngeal ring in long-term exposure to low-dose
      radiation. Chronic disease of the tonsils and adenoids was detected in 194
      children (45.4%). Chronic tonsillitis was diagnosed in 142 (33.3%) examinees.
      31.7 and 59.9% cases had compensated and subcompensated disease. Decompensated
      process took place in 8.5% cases of chronic tonsillitis. Hypertrophy of the
      palatine tonsils and adenoids was detected in 96 (22.5%) children. High incidence
      of lymphadenopathy of the neck in combination with chronic tonsillitis and tonsil
      and adenoid hypertrophy was found. Structure of chronic pathology of the lymphoid
      pharyngeal ring correlated with internal radiation dose. Comparison of
      postnatally and antenatally radiated children demonstrated less frequent
      incidence of affected lymphoid pharyngeal ring in children born before the
      Chernobyl accident.

PMID- 15496832
TI  - [Evoked otoacoustic emission in conduction of dehydration tests in patients with
      Meniere's disease].
AB  - We studied potentiality of the test of evoked otoacoustic emission (EOAE) for
      monitoring of dynamic changes in the internal ear in conduction of dehydration
      tests. In parallel to registration of tonal hearing thresholds and speech
      intelligibility in conduction of dehydration tests we registered two classes of
      EOAE: delayed EOAE (DEOAE) and distortion product otoacoustic emission (DPOAE).
      Of 36 examinees, we registered DEOAE prior to dehydration in 22 patients. By
      audiometry, these patients had hearing under 40 dB lower the hearing threshold at
      frequencies 250-4000 Hz. In registration of DEOAE in dynamics a maximal amplitude
      increase was seen 2 hours after intake of glycerin. A mean amplitude increase was
      7.0+/-2.3 dB. Before dehydration DEOAE was recorded in 26 of 36 patients. Two
      hours laser otoacoustic response was registered in 29 patients. Hearing loss was
      not more than 60 dB at frequencies 250-4000 Hz. A maximal amplitude increase was
      seen in 2 hours. A mean amplitude increase in dehydration was 7.3+/-3.7 dB.

PMID- 15496833
TI  - [Taurine effects on background impulse activity of the internal geniculate body
      neurons and mesencephalic inferior tubers of white rats].
AB  - Microelectrophysiological and computer techniques were used in the study of
      background impulse activity (BIA) of the internal geniculate body (IGB) neurons
      and mesencephalic inferior tubers (MIT) of white rats. Definite differences were
      found in BIA by regularity, dynamic types and modality of interimpulse
      histograms. Mean frequency of MIT neuron discharges was 16-17 Hz and was about 3
      times higher than in neurons of the IGB. Intraperitoneal injection of taurin
      noticeably suppressed neuronal activity in both nuclei. The drug reduced mean
      frequency of background impulse discharges both in MIT and IGB. Thus, taurin
      produces primarily suppressing modulating effect on neuronal activity of IGB and
      MIT.

PMID- 15496834
TI  - [Visualization of the operative field by adenotome of a new design].
AB  - The article describes design characteristics of a new adenotome model for surgery
      under anesthesia. The results of adenotomy under anesthesia were analysed for 53
      patients aged 3 to 14 years made with Beckman's adenotome and the new device.
      Surgical anatomy of the nasopharynx before the intervention, variants of
      correlations between adenoid vegetations and other anatomic formations are
      described. Individual adjustment of the size of the adenotome currete by the
      distance between Eustachian cushins of the nasopharynx is discussed. The new
      design of adenotome improves visualization of the operative field during the
      operation and visual control of the course of surgery.

PMID- 15496835
TI  - [A new outlook on adenoid hypertrophy: adenoids or adenoid disease?].
AB  - Hypertrophy of the pharyngeal tonsil affects functions of some organs and systems
      producing negative effects on physical and mental development of the child. The
      existing classification based of the tonsil size does not reflect the complexity
      of the pathological process. "Adenoid disease" is thought to be a more adequate
      term. A new classification of adenoid disease is proposed. Indications for
      conservative and surgical treatments can be well formulated with the new
      classification. The authors prefer adenotomy as, in their opinion, adenectomy is
      not safe for health.

PMID- 15496836
TI  - [Computed tomography of the temporal bone in diagnosis of otitis media chronica
      purulenta].
AB  - Computed tomography (CT) of the temporal bone has been used to study thirty-eight
      5-72-year-old patients with otitis media chronica purulenta (OMCP), in 14 of them
      the process was bilateral. A scheme of CT assessment of the temporal bone is
      proposed. The analysis of 52 CTs of the temporal bone with consideration of
      otoscopic and operative findings helped to distinguish CT signs of non
      cholesteatomic OMCP. These signs include sclerotic alterations of the bone tissue
      of the mastoid process (82.7%), defective pneumaticity of the middle ear cavities
      (tympanic cavity - 80.7%) due to pathological substrate, destructive changes of
      the auditory bones (50%), carious alterations of the walls of the middle ear
      cavities (21%). The study of the temporal bone by the proposed scheme detected
      such anomalies and structural features as presentation of the sigmoid sinus
      (36.5%), elevation of the bulb of the jugular vein (3.8%), diverticulum of the
      jugular vein (3.8%), low fundus of the middle cranial fossa (7.7%).

PMID- 15496837
TI  - [Concomitant labyrinthitis].
AB  - The principal pathogenetic mechanism of labyrinthopaty development after traumas
      and operations lies in autoimmune inflammation of the contralateral ear similar
      to sympathetic inflammation of the eye. By analogy with sympathetic ophthalmitis,
      a term <<concomitant labyrinthitis>> is proposed. Due to selective permeability
      of selective membranes, immune system has no connection with <<extrabarrier>>
      organs. These organs and tissues are isolated from the key sourse of immunity --
      blood. Autotolerance to them is absent and their proteins are autoantigens. In
      destruction of hemato-labyrinthine barrier these autoantigens can reach lymphoid
      organs and provoke immune response inducing a cytotoxic action in relation to
      both the affected and the contralateral labyrinth. Besides pathology of the
      affected labyrinth, clinical picture of labyrinthopathy is caused by autoimmune
      labyrinthitis of the contralateral ear whereas in <<dead>> labyrinthitis of the
      affected ear - slow-progressive autoimmune concomitant labyrinthitis. Case
      reports are presented.

PMID- 15496838
TI  - [Pathogenetic aspects of treating patients with neurosensory hypoacusis].
AB  - Homeostatic examination of the blood was made with conventional methods in 115
      patients with acute and chronic neurosensory hypoacusis. Statistically
      significant changes of hemostasis, blood rheology and lipid spectrum were
      detected. Causes of acute and chronic progressive neurosensory hypoacusis in some
      patients are discussed. The above changes should be taken into account when
      planning medication.

PMID- 15496839
TI  - [Phenomenon of calcification of the stylohyoid ligament].
AB  - Patients with continuous pain in the pharynx were examined roentgenologically for
      calcification of the stylohyoid ligaments and the styloid process. Symptoms and
      surgical outcomes are described in cases with calcification of the stylohyoid
      process and muscle. Surgical treatment eliminated pain, noise in the ears,
      chronic pharyngeal inflammation. No recurrences occurred. Histological
      examination of the removed stylohyoid ligaments detected calcificated hyalin
      plaques in these ligaments.

PMID- 15496840
TI  - [The study of mucociliary clearance of maxillary mucosa with radionuclide dynamic
      maxillary scintigraphy of various forms of maxillary sinusitis].
AB  - Mucociliary transport and absorption of maxillary mucosa were studied in patients
      with different forms of maxillary sinusitis. Radionuclide dynamic maxillary
      scintigraphy specified functional characteristics of maxillary mucosa in respect
      to the form of its inflammation.

PMID- 15496842
TI  - [Our experience using triderm for the treatment of external otitis].

PMID- 15496841
TI  - [Pharmacological correction of cochleovestibular impairments].

PMID- 15496843
TI  - [Use of the drug otipax in acute otitis media in newborns and infants].

PMID- 15496844
TI  - [Elimination therapy in the treatment of adenoiditis in children with acute
      sinusitis].

PMID- 15496845
TI  - [Field of view of the otorhinolaryngologist in the evolutionary aspect].

PMID- 15496846
TI  - [Approaches to rehabilitation of patients beginning to use hearing aids].

PMID- 15496847
TI  - [Non-Hodgkin's lymphoma of the Pirogov-Waldeyer pharyngeal ring].

PMID- 15496848
TI  - [A case of lipoma of deep fat of the neck].

PMID- 15496849
TI  - [Professor Nikolai Alekseevich Nikolaev].

PMID- 15496850
TI  - Introduction and methodologic aspects of the consensus document. Spanish
      consensus panel on erectile dysfunction.

PMID- 15496851
TI  - Specific aspects of erectile dysfunction in endocrinology.
AB  - Prominent diseases of the endocrine system, such as diabetes mellitus,
      hypogonadism, and hyperprolactinemia, may cause erectile dysfunction (ED). ED
      affects about 50% of male diabetic patients possibly due to the vascular and
      neuropathic complications. Metabolic control and selective phosphodiesterase type
      5 inhibitors are therapies of choice for controlling ED. By correcting
      hypogonadism, testosterone levels are restored. This, and the use of dopaminergic
      drugs, which normalize prolactin levels in male hyperprolactinemia, may be
      effective in reversing ED in these endocrine disorders.

PMID- 15496852
TI  - Erectile dysfunction in heart disease patients.
AB  - Atherosclerosis is a general health problem that not only affects the coronary
      arteries but also (in men) the penile arteries, thus contributing to organic
      causes of erectile dysfunction (ED) in heart disease patients. These organic
      causes are intertwined with psychological and pharmacological causes because
      medication prescribed for heart disease patients may also cause ED. The incidence
      of ED after myocardial infarction ranges from 38 to 78%. As sexual intercourse
      involves physical exertion, the medical history, ventricular function determined
      through echocardiography, and stress testing are used to classify patients into
      various groups where coital activity represents a greater or lesser
      cardiovascular risk. The energy requirements for intercourse are not high,
      ranging from 3.7 metabolic equivalents (METs) of energy expenditure at resting
      state during the preorgasmic phase to 5 METs during orgasm. The Bruce protocol
      for exercise stress testing is a six-stage protocol with changes in the slope and
      speed of the treadmill. As a general rule, a patient who completes the first two
      stages of the Bruce protocol has a functional capacity greater than 7 METs, which
      is considered sufficient for sexual intercourse. The physician or cardiologist
      concerned should institute first-line treatment with oral drugs according to the
      indications listed below. If sexual activity is not contraindicated, the
      treatment of choice for ED in heart disease patients is oral therapy with
      sildenafil, except in those cases in which its use is contraindicated. Specific
      recommendations are discussed.

PMID- 15496853
TI  - Specific aspects of erectile function in urology/andrology.
AB  - The urologist/andrologist is the specialist responsible for diagnosis and
      treatment of health problems related to the genitourinary tract, and his or her
      participation in comprehensive care for a patient with erectile dysfunction (ED)
      is fundamental and often indispensable. The urologists/andrologists should
      characterize the origin of ED because of their knowledge and familiarity of all
      diagnostic tests and second- and third-line therapy. The origin of ED is
      important to determine for various reasons, such as young people suitable for
      etiologic treatment, medicolegal reasons, or patients' wishes for a better
      understanding of their condition. A review of the diagnostic tests available as
      well as indications for second- and third-line therapy is presented. The close
      relationship between ED and urological disorders, such as benign prostatic
      hyperplasia, prostate cancer and their treatments, and renal failure, in
      association with penile conditions like Peyronie's disease, priapism, and
      possible androgen deficiency in men older than 50 years, places the urologist at
      the center of integrated treatment of male ED.

PMID- 15496854
TI  - Core document on erectile dysfunction: key aspects in the care of a patient with
      erectile dysfunction.
AB  - The aim of this Core Document of the Spanish Consensus on Erectile dysfunction
      (ED) is to offer guidance to the nonspecialist physician in the management of
      patients with ED. ED is one of the most frequent chronic health problems in men
      older than 40 y of age and may also act as a sentinel symptom for other important
      underlying diseases. Its etiology can be classified into organic, psychogenic, or
      mixed. In most cases, the underlying cause of ED is usually a chronic health
      problem (such as diabetes, hypertension, atherosclerosis, and so on) or an
      adverse drug effect. The initial step in the management is to assess erectile
      function in patients with risk factors for ED. Once ED has been established, a
      detailed sexual, medical, and social history, including a review of medications
      used, is the most important aspect of a patient's assessment. Generally,
      examination should be limited to the cardiovascular, neurological, and urogenital
      systems. Fasting glucose and blood lipid profile should be performed in every man
      with ED, and free testosterone levels in men older than 50 y or if hypogonadism
      is suspected; other diagnostic tests are optional and should be requested on an
      individualized basis. In many cases, the most likely cause of ED can be
      identified based on the above information. Therapeutic intervention should be
      patient-oriented and based on the expectations and wishes of the patient and his
      partner, who should be included in discussions whenever possible. Basic
      interventions common to any type of ED include sexual counseling, lifestyle
      modifications, treatment of associated medical conditions, and switching to
      alternative drugs with lower risk of ED. In certain cases, an etiologic treatment
      may be performed (sex therapy, revascularization surgery, and hormonal therapy).
      Most patients with ED will benefit from symptomatic treatments; first-line
      therapy may be prescribed by physicians who are not specialists in ED, and
      includes oral agents such as inhibitors of phosphodiesterase type 5, currently
      considered the drugs of choice for initial treatment of ED. Intracavernous drugs
      are the second-line therapy, and surgical treatments, such as implantation of
      penile prostheses, are reserved for urologists/andrologists who specialize in ED.
      Referral may be appropriate where indicated by age, clinical findings, or the
      patient's request.

PMID- 15496855
TI  - Specific aspects of erectile dysfunction in sexology.
AB  - The sexology of erectile dysfunction (ED) is approached from a perspective that
      integrates medical, psychological, and social aspects. This article reviews the
      clinical intervention in sexology beginning with the diagnostic evaluation, where
      the organic and psychological factors (predisposing, precipitating, and
      perpetuating) contributing to ED are determined. A description of the
      differential diagnosis process follows, which establishes the relevance of
      organic factors in order to organize therapeutic strategies. There are three
      possible treatment processes: psychological intervention with the patient,
      intervention on the partner relationship, or intervention with the partner.
      Referral criteria are also described, such as when patients with ED should be
      referred to a sexologist, and to whom sexologists should refer patients with ED.

PMID- 15496856
TI  - Erectile dysfunction: information for the health administration.

PMID- 15496857
TI  - Specific aspects of erectile dysfunction in spinal cord injury.
AB  - According to preliminary studies, the overall incidence of spinal cord injury
      (SCI; traumatic and medical) in Spain is estimated to be between 12 and 20 per
      million inhabitants, and almost 80% of these injuries occur in young men. SCI
      causes organic changes in men leading to erectile dysfunction (ED), impaired
      ejaculation, and changes in genital orgasmic perception. A vast majority of men
      with both complete and incomplete SCI will require treatment for ED, and the
      therapeutic options should include sexual counseling so that the patient can be
      informed about his disorder and can adjust his sexual behavior accordingly. The
      first-line treatment of choice is oral drugs, such as phosphodiesterase
      inhibitors (sildenafil, tadalafil, and vardenafil). Sildenafil has been shown to
      be highly effective and well tolerated in men with ED of various etiologies,
      including SCI. Data are also presented on sublingual apomorphine, which has
      limited indications for the treatment of ED in SCI, and on constrictive rings and
      vacuum systems. Second-line treatments include intracavernous injections of
      prostaglandin E(1), papaverine, and phentolamine, alone or in combination, which
      have been shown to be highly effective in the treatment of ED in men with SCI.
      Finally, for third-line treatments, the indications for surgical methods are
      given, including penile prostheses and neuroprosthesis of anterior sacral roots.
      These devices should be reserved for the cases when the above-mentioned methods
      have repeatedly failed. Historically, the treatment of ED among patients with SCI
      has been managed by clinicians in physical medicine and rehabilitation. Thus, the
      criteria for referral and the competencies of these specialists are established,
      and they should be included as an integral part of the rehabilitation program.

PMID- 15496858
TI  - Specific aspects of erectile dysfunction in psychiatry.
AB  - The participation of the psychiatrist in the management of erectile dysfunction
      (ED) is focused on three types of patients based on the origin of the
      dysfunction: (1) patients with functional or psychogenic ED, (2) patients with
      mixed, organic psychogenic ED, and (3) patients with ED and active
      psychopathology. The second group is influenced by three psychological factors:
      perpetuating factors, aggravating factors, and accompanying factors. The main
      psychopathological disorders that interfere directly with the erectile mechanism
      are depressive disorders (18-35%), anxiety disorders (37%), obsessive-compulsive
      disorder, psychotic disorders (46-47%), and the antipsychotic medications used to
      treat these disorders. The diagnostic proposal includes psychological and
      sexologic evaluation and differential diagnosis. The therapeutic proposal
      includes the basic principles of sex therapy in the model of behavioral-cognitive
      therapy (eg, prohibition of intercourse, sensate focus, voluntary loss of
      erections, no expectations about response), pharmacological therapy (eg,
      sildenafil, intracavernous injection of vasoactive drugs), and a combination of
      both therapies.

PMID- 15496859
TI  - Specific aspects of erectile dysfunction and its treatment for community
      pharmacists.
AB  - We reviewed several topics relating to erectile dysfunction (ED) and its
      treatment, which are of interest to the community pharmacy. First, we analyze the
      community pharmacy's role as a center of health education to the population.
      Second, we discuss the legal aspects of medical prescription for drugs not
      financed by the Spanish National Health Service. Finally, we explain how
      community pharmacists may inform patients on the proper use of prescribed
      medicines for ED and any medications that may cause interactions or should be
      avoided with treatment.

PMID- 15496860
TI  - Document for the general public. Spanish consensus panel on erectile dysfunction.

PMID- 15496861
TI  - Early language acquisition: cracking the speech code.
AB  - Infants learn language with remarkable speed, but how they do it remains a
      mystery. New data show that infants use computational strategies to detect the
      statistical and prosodic patterns in language input, and that this leads to the
      discovery of phonemes and words. Social interaction with another human being
      affects speech learning in a way that resembles communicative learning in
      songbirds. The brain's commitment to the statistical and prosodic patterns that
      are experienced early in life might help to explain the long-standing puzzle of
      why infants are better language learners than adults. Successful learning by
      infants, as well as constraints on that learning, are changing theories of
      language acquisition.

PMID- 15496862
TI  - Neuronal signalling of fear memory.
AB  - The learning and remembering of fearful events depends on the integrity of the
      amygdala, but how are fear memories represented in the activity of amygdala
      neurons? Here, we review recent electrophysiological studies indicating that
      neurons in the lateral amygdala encode aversive memories during the acquisition
      and extinction of Pavlovian fear conditioning. Studies that combine unit
      recording with brain lesions and pharmacological inactivation provide evidence
      that the lateral amygdala is a crucial locus of fear memory. Extinction of fear
      memory reduces associative plasticity in the lateral amygdala and involves the
      hippocampus and prefrontal cortex. Understanding the signalling of aversive
      memory by amygdala neurons opens new avenues for research into the neural systems
      that support fear behaviour.

PMID- 15496863
TI  - Specificity of priming: a cognitive neuroscience perspective.
AB  - Priming is a nonconscious form of memory that involves a change in a person's
      ability to identify, produce or classify an item as a result of a previous
      encounter with that item or a related item. One important question relates to the
      specificity of priming - the extent to which priming reflects the influence of
      abstract representations or the retention of specific features of a previous
      episode. Cognitive neuroscience analyses provide evidence for three types of
      specificity: stimulus, associative and response. We consider empirical,
      methodological and conceptual issues that relate to each type of specificity, and
      suggest a theoretical perspective to help in guiding future research.

PMID- 15496864
TI  - Iron, brain ageing and neurodegenerative disorders.
AB  - There is increasing evidence that iron is involved in the mechanisms that
      underlie many neurodegenerative diseases. Conditions such as neuroferritinopathy
      and Friedreich ataxia are associated with mutations in genes that encode proteins
      that are involved in iron metabolism, and as the brain ages, iron accumulates in
      regions that are affected by Alzheimer's disease and Parkinson's disease. High
      concentrations of reactive iron can increase oxidative-stress induced neuronal
      vulnerability, and iron accumulation might increase the toxicity of environmental
      or endogenous toxins. By studying the accumulation and cellular distribution of
      iron during ageing, we should be able to increase our understanding of these
      neurodegenerative disorders and develop new therapeutic strategies.

PMID- 15496865
TI  - VSDI: a new era in functional imaging of cortical dynamics.
AB  - During the last few decades, neuroscientists have benefited from the emergence of
      many powerful functional imaging techniques that cover broad spatial and temporal
      scales. We can now image single molecules controlling cell differentiation,
      growth and death; single cells and their neurites processing electrical inputs
      and sending outputs; neuronal circuits performing neural computations in vitro;
      and the intact brain. At present, imaging based on voltage-sensitive dyes (VSDI)
      offers the highest spatial and temporal resolution for imaging neocortical
      functions in the living brain, and has paved the way for a new era in the
      functional imaging of cortical dynamics. It has facilitated the exploration of
      fundamental mechanisms that underlie neocortical development, function and
      plasticity at the fundamental level of the cortical column.

PMID- 15496866
TI  - What is an auditory object?
AB  - Objects are the building blocks of experience, but what do we mean by an object?
      Increasingly, neuroscientists refer to 'auditory objects', yet it is not clear
      what properties these should possess, how they might be represented in the brain,
      or how they might relate to the more familiar objects of vision. The concept of
      an auditory object challenges our understanding of object perception. Here, we
      offer a critical perspective on the concept and its basis in the brain.

PMID- 15496867
TI  - Antenatal risk factors associated with the development of lenticulostriate
      vasculopathy (LSV) in neonates.
AB  - OBJECTIVE: To determine the antenatal risk factors associated with neonatal
      lenticulostriate vasculopathy (LSV). STUDY DESIGN: Women in preterm labor were
      randomized to magnesium sulfate (MgSO4), other tocolytic, or saline control. The
      surviving babies underwent head ultrasounds (HUS) (weeks of life 1, 2, and 4) and
      periodic developmental examinations (months 4, 8, 12, and 18). RESULTS: Of 140
      infants, 17.1% (24) had neonatal intraventricular hemorrhage (IVH), and 10.0%
      (14) had LSV (half of the latter (7 of 14) had both IVH and LSV). In a regression
      model in which other risk factors were controlled for, the association between
      antenatal exposures to tocolytic MgSO4 >or=50 g and LSV were significant
      (adjusted odds ratio (OR), 8.3; 95% confidence interval (CI), 1.5 to 45.0;
      p=0.01). CONCLUSION: Based on our data and their analyses, we infer that
      antenatal exposure to high-dosage, tocolytic MgSO4 may be associated with LSV.

PMID- 15496868
TI  - Effect of instrument precision on estimation of low birth weight prevalence.
AB  - OBJECTIVE: Reductions in prevalence of low birth weight (LBW) are likely to be
      achieved only through small increments, amplifying the importance of precision of
      measurement. This study compared two instruments for measuring birth weight to
      investigate the effect of instrument precision on estimates of LBW prevalence.
      STUDY DESIGN: Analysis was based on 497 infants born to mothers enrolled in an
      ongoing community-based trial of the effect of umbilical cord and skin antisepsis
      on neonatal mortality in Nepal. For each child, two birth weight measurements
      were recorded within 72 hours after delivery using weighing scales of differing
      precisions (100 vs 2 g). RESULTS: While continuous measures between the two
      instruments were similar, the prevalence of LBW among lower precision
      measurements (30%) was 11.3% lower than for higher precision measurements (34%).
      The difference in precision between the instruments accounted for 96% of the
      difference in LBW prevalence estimates. CONCLUSIONS: Differences in estimated LBW
      rates may be entirely due to differences in instrument precision. Conclusions
      concerning programmatic or research intervention impact, or comparisons of rates
      across populations should consider the effect of instrument precision on
      estimates of LBW.

PMID- 15496869
TI  - Follow-up of infants exposed to hydroxychloroquine given to mothers during
      pregnancy and lactation.
AB  - OBJECTIVE: To determine the effect of hydroxychloroquine treatment during
      pregnancy and lactation on babies of mothers affected by rheumatic diseases.
      STUDY DESIGN AND METHODS: A total of 40 infants born from mothers affected by
      rheumatic diseases and treated with hydroxychloroquine during pregnancy were
      enrolled in a prospective observational study. Main outcome measures at birth
      were incidence of prematurity, congenital malformations and neonatal infections.
      Of these babies, including 13 who were breast-fed, 24 were followed up during
      early infancy for visual function and neurodevelopmental outcome. RESULTS:
      Preterm delivery was the main complication (20.5%). No significant congenital
      malformations or neonatal infections were detected. All infants, including those
      who were breast-fed, had normal visual function and neurodevelopmental outcome.
      CONCLUSIONS: Hydroxychloroquine treatment during gestation and lactation appeared
      to be safe. The relatively high incidence of preterm deliveries may reflect the
      maternal disease state.

PMID- 15496870
TI  - Twelve-month prospective study of oxygen saturation measurements among term and
      preterm infants.
AB  - BACKGROUND: Optimising home oxygen delivery in infants has important logistical
      and safety implications. This can be aided by having a suitable reference range
      of normal values for arterial oxygen saturation using pulse oximetry (SpO(2)).
      OBJECTIVES: To describe oxygenation profiles in healthy preterm and term infants
      in relation to gestational and postnatal age, to extend reference values to guide
      home oxygen therapy. STUDY DESIGN: Prospective monitoring of SpO(2) for 4 hours
      at 3 monthly intervals of 34 term, and 53 preterm healthy infants, took place
      over a 12-month period using an Ohmeda Biox 3700e pulse oximeter and data logger.
      RESULTS: Group mean and 5th percentiles were used to construct cumulative
      frequency curves at each time interval, representing the normal reference range
      of SpO(2) profiles for term and preterm infants over time. CONCLUSIONS: These
      data may be used to test the benefits in the home or hospital of having a
      reference range of normal values for cumulative SpO(2).

PMID- 15496871
TI  - Indicated and non-indicated preterm delivery in twin gestations: impact on
      neonatal outcome and cost.
AB  - OBJECTIVE: To identify the etiology and impact of preterm delivery in twin
      gestations. STUDY DESIGN: Twin gestations delivered at 33.0 to 36.9 weeks were
      identified in a perinatal database, and categorized by indication for delivery.
      Deliveries were identified as indicated, or non-indicated (discretionary).
      Neonatal outcomes were measured by birth weight, length of stay, NICU admission,
      and ventilator utilization. Data were divided and analyzed by indicated or
      discretionary delivery, and gestational age at delivery. RESULTS: Analyzed were
      3252 twin gestations (6504 infants), with 78% having indicated delivery. Of the
      22% with discretionary delivery, nearly 40% required NICU admission. With each
      advancing week of gestation, there was a significant decrease in incidence of
      NICU admission and nursery days. CONCLUSION: The majority of preterm deliveries
      were indicated, though 22% were discretionary. It is vital to consider neonatal
      morbidity and costs related to gestational age when choosing discretionary
      delivery.

PMID- 15496872
TI  - The impact of hydramnios on pregnancy outcome in twin gestations.
AB  - OBJECTIVE: To compare pregnancy outcome in twin pregnancies with and without
      hydramnios. STUDY DESIGN: A database of women receiving outpatient preterm labor
      surveillance services was studied for the period 1988 to 2002. Included were
      women with twin gestations under 30 weeks' gestation at start of outpatient
      services. We compared pregnancy outcomes for twin gestations with hydramnios
      (n=201) to twin gestations that had normal amniotic fluid volume (n=13,111).
      RESULTS: Obstetrical and perinatal outcomes in twin pregnancies were adversely
      affected by the presence of hydramnios. Delivery was shifted to earlier
      gestations in women with hydramnios (32.8 vs 35.1 weeks, p<0.001), especially
      under 32 weeks (38.3 vs 12.7%). Perinatal loss was notable in women with
      hydramnios: stillbirths (12.7 vs 1.1%, p<0.001) and neonatal mortality (7.5 vs
      1.1%, p<0.001). CONCLUSIONS: Hydramnios in twin gestations negatively impacts
      gestational age at delivery. The incidence of perinatal mortality is
      significantly increased in the presence of hydramnios.

PMID- 15496873
TI  - Barriers to screening infants for retinopathy of prematurity after discharge or
      transfer from a neonatal intensive care unit.
AB  - OBJECTIVE: To assess neonatal intensive care unit (NICU) practices affecting
      screening and follow-up for retinopathy of prematurity (ROP). METHODS:
      Retrospective study of infants at risk for ROP, eligible for back transport,
      admitted to a regional NICU from January 1, 1999 until May 31, 2002. Patients
      failed to receive needed follow-up for ROP after discharge or transfer from a
      NICU, if we could not verify their ROP screening follow-up within 1 month.
      RESULTS: A total of 74 infants were identified to need follow-up eye care.
      Infants who did not receive the follow-up care had greater mean gestational age
      (mean SD; 30.7+/-2.3 vs 29.6+/-2.5 weeks, p=0.05) and birth weights (mean SD;
      1581+/-366 vs 1360+/-508 g, p=0.007), compared to infants who received the
      recommended care. Infants transported back to the community hospital were
      significantly more likely to miss follow-up eye care compared to infants
      discharged from the regional center (relative risk 2.81, 95% confidence interval
      (CI) (1.09 to 7.20)). Infants not screened for ROP in the NICU had greater risk
      for missing follow-up care compared to infants who had their first retinal
      examination in the NICU (relative risk 4.25, 95% CI (1.42 to 12.73)).
      CONCLUSIONS: Infants transferred back or discharged from the NICU before ROP
      screening represent a high-risk group for not receiving follow-up eye care.

PMID- 15496874
TI  - Agreement of carbon dioxide levels measured by arterial, transcutaneous and end
      tidal methods in preterm infants < or = 28 weeks gestation.
AB  - OBJECTIVE: To assess the agreement of transcutaneous carbon dioxide (TcPCO(2))
      and end tidal carbon dioxide (PetCO(2)) with arterial carbon dioxide (PaCO(2))
      values in infants < 28 weeks gestational age. STUDY DESIGN: In all, 27 ventilated
      preterm infants were prospectively studied. PaCO(2) was compared with TcPCO(2)
      and PetCO(2) measured at three similar time points within first 24 hours after
      birth. RESULTS: The Intraclass correlation coefficients for TcPCO(2) and PaCO(2)
      were 0.45, 0.73 and 0.53; and for PetCO(2) and PaCO(2) were 0.61, 0.56 and 0.57
      at 4, 12 and 24 hours after birth, respectively. CONCLUSION: A moderate agreement
      with a wide variation in individual values was observed between noninvasive
      methods and PaCO(2) in preterm infants in the first 24 hours. Noninvasive
      monitoring methods cannot be substituted for PaCO(2) analyses in preterm infants
      during this critical period.

PMID- 15496875
TI  - Reduction in red blood cell transfusions using a bedside analyzer in extremely
      low birth weight infants.
AB  - BACKGROUND: Preterm infants typically experience heavy phlebotomy losses from
      frequent laboratory testing in the first few weeks of life. This results in
      anemia, requiring red blood cell (RBC) transfusions. We recently introduced a
      bedside point-of-care (POC) blood gas analyzer (iSTAT, Princeton, NJ) that
      requires a smaller volume of blood to replace conventional Radiometer blood gas
      and electrolyte analysis used by our neonatal intensive care unit (NICU). The
      smaller volume of blood required for sampling (100 vs 300-500 microl), provided
      an opportunity to assess if a decrease in phlebotomy loss occurred and, if so, to
      determine if this resulted in decreased transfusions administered to extremely
      low birth weight (ELBW) infants. OBJECTIVE: We hypothesized that the use of the
      POC iSTAT analyzer that measures pH, PCO(2), PO(2), hemoglobin, hematocrit, serum
      sodium, serum potassium and ionized calcium would result in a significant
      decrease in the number and volume of RBC transfusions in the first 2 weeks of
      life. DESIGN/METHODS: A retrospective chart review was conducted of all inborn
      premature infants with birth weights less than 1000 g admitted to the NICU that
      survived for 2 weeks of age during two separate 1-year periods. Blood gas
      analysis was performed by conventional laboratory methods during the first period
      (designated Pre-POC testing) and by the iSTAT POC device during the second period
      (designated post-POC testing). Data collected for individual infants included the
      number of RBC transfusions, volume of RBCs transfused, and the number and kind of
      blood testing done. There was no effort to change either the RBC transfusion
      criteria applied or blood testing practices. RESULTS: The mean (+/-SD) number of
      RBC transfusions administered in the first 2 weeks after birth was 5.7+/-3.74
      (n=46) in the pre-POC testing period to 3.1+/-2.07 (n=34) in the post-POC testing
      period (p<0.001), a 46% reduction. The mean volume of RBC transfusions decreased
      by 43% with use of the POC analyzer, that is, from 78.4+/-51.6 ml/kg in the pre
      POC testing group to 44.4+/-32.9 ml/kg in the Post-POC testing group (p<0.002).
      There was no difference between the two periods in the total number of laboratory
      blood tests done. CONCLUSIONS: Use of a bedside blood gas analyzer is associated
      with clinically important reductions in RBC transfusions in the ELBW infant
      during the first two weeks of life.

PMID- 15496876
TI  - Phosphorylation-dependent binding of mitotic cyclins to Cdc6 contributes to DNA
      replication control.
AB  - Cyclin-dependent kinases (CDKs) limit the activation of DNA replication origins
      to once per cell cycle by preventing the assembly of pre-replicative complexes
      (pre-RCs) during S, G2 and M phases of the cell cycle in the budding yeast
      Saccharomyces cerevisiae. CDKs inhibit each pre-RC component (ORC, Cdc6,
      Cdt1/Mcm2-7) by different mechanisms. We show here that the mitotic CDK,
      Clb2/Cdc28, binds tightly to an amino-terminal domain (NTD) of Cdc6, and that
      Cdc6 in this complex is unable to assemble pre-RCs. We present evidence
      indicating that this Clb2-dependent mechanism contributes to preventing re
      replication in vivo. CDK interaction with the NTD of Cdc6 is mediated by the
      cyclin subunit Clb2, and could be reconstituted with recombinant Clb2 protein and
      synthetic NTD peptides. Tight Clb2 binding occurred only when the NTD was
      phosphorylated on CDK consensus sites. Human CDKs containing cyclins A, B and E
      also bound specifically to phospho-NTD peptides. We propose that direct binding
      of cyclins to phosphopeptide motifs may be a widespread phenomenon contributing
      to the targeting of CDKs to substrates.

PMID- 15496877
TI  - Going public.

PMID- 15496878
TI  - Biologists seek consensus on guidelines for stem-cell research.

PMID- 15496879
TI  - Early success claimed for Zerhouni's NIH roadmap.

PMID- 15496880
TI  - Infertility specialists counsel caution over frozen eggs.

PMID- 15496881
TI  - French delegation strengthens bond with China.

PMID- 15496882
TI  - Russians fear privatization of state labs.

PMID- 15496883
TI  - Germany balks at funding ESA's planetary ambitions.

PMID- 15496884
TI  - Schwarzenegger endorses stem-cell push.

PMID- 15496885
TI  - Germany's junior professors fight for their rights.

PMID- 15496886
TI  - Quarrel over book leads to call for misconduct inquiry.

PMID- 15496888
TI  - Antibiotics: a shot in the arm.

PMID- 15496889
TI  - Genetics: deaf by design.

PMID- 15496890
TI  - Today is the time to take environmental action.

PMID- 15496891
TI  - US restrictions limit anthrax networking.

PMID- 15496892
TI  - The real dirty secret of academic publishing.

PMID- 15496893
TI  - Antibiotics at the crossroads.

PMID- 15496901
TI  - Climbing the co-evolution ladder.

PMID- 15496902
TI  - Human genome: end of the beginning.

PMID- 15496903
TI  - Comparative genomics: small genome, big insights.

PMID- 15496905
TI  - General relativity: frame-dragging confirmed.

PMID- 15496906
TI  - Cancer: negative feedback for B cells.

PMID- 15496907
TI  - Climate: wider connections for El Nino.

PMID- 15496908
TI  - Physiology: joint approach.

PMID- 15496909
TI  - Obituary: Maurice Wilkins (1916-2004).

PMID- 15496911
TI  - Palaeontology: leg feathers in an Early Cretaceous bird.
AB  - Here we describe a fossil of an enantiornithine bird from the Early Cretaceous
      period in China that has substantial plumage feathers attached to its upper leg
      (tibiotarsus). The discovery could be important in view of the relative length
      and aerodynamic features of these leg feathers compared with those of the small
      'four-winged' gliding dinosaur Microraptor and of the earliest known bird,
      Archaeopteryx. They may be remnants of earlier long, aerodynamic leg feathers, in
      keeping with the hypothesis that birds went through a four-winged stage during
      the evolution of flight.

PMID- 15496912
TI  - Shotgun sequence assembly and recent segmental duplications within the human
      genome.
AB  - Complex eukaryotic genomes are now being sequenced at an accelerated pace
      primarily using whole-genome shotgun (WGS) sequence assembly approaches. WGS
      assembly was initially criticized because of its perceived inability to resolve
      repeat structures within genomes. Here, we quantify the effect of WGS sequence
      assembly on large, highly similar repeats by comparison of the segmental
      duplication content of two different human genome assemblies. Our analysis shows
      that large (> 15 kilobases) and highly identical (> 97%) duplications are not
      adequately resolved by WGS assembly. This leads to significant reduction in
      genome length and the loss of genes embedded within duplications. Comparable
      analyses of mouse genome assemblies confirm that strict WGS sequence assembly
      will oversimplify our understanding of mammalian genome structure and evolution;
      a hybrid strategy using a targeted clone-by-clone approach to resolve
      duplications is proposed.

PMID- 15496913
TI  - Finishing the euchromatic sequence of the human genome.
AB  - The sequence of the human genome encodes the genetic instructions for human
      physiology, as well as rich information about human evolution. In 2001, the
      International Human Genome Sequencing Consortium reported a draft sequence of the
      euchromatic portion of the human genome. Since then, the international
      collaboration has worked to convert this draft into a genome sequence with high
      accuracy and nearly complete coverage. Here, we report the result of this
      finishing process. The current genome sequence (Build 35) contains 2.85 billion
      nucleotides interrupted by only 341 gaps. It covers approximately 99% of the
      euchromatic genome and is accurate to an error rate of approximately 1 event per
      100,000 bases. Many of the remaining euchromatic gaps are associated with
      segmental duplications and will require focused work with new methods. The near
      complete sequence, the first for a vertebrate, greatly improves the precision of
      biological analyses of the human genome including studies of gene number, birth
      and death. Notably, the human genome seems to encode only 20,000-25,000 protein
      coding genes. The genome sequence reported here should serve as a firm foundation
      for biomedical research in the decades ahead.

PMID- 15496915
TI  - A confirmation of the general relativistic prediction of the Lense-Thirring
      effect.
AB  - An important early prediction of Einstein's general relativity was the advance of
      the perihelion of Mercury's orbit, whose measurement provided one of the
      classical tests of Einstein's theory. The advance of the orbital point-of-closest
      approach also applies to a binary pulsar system and to an Earth-orbiting
      satellite. General relativity also predicts that the rotation of a body like
      Earth will drag the local inertial frames of reference around it, which will
      affect the orbit of a satellite. This Lense-Thirring effect has hitherto not been
      detected with high accuracy, but its detection with an error of about 1 per cent
      is the main goal of Gravity Probe B--an ongoing space mission using orbiting
      gyroscopes. Here we report a measurement of the Lense-Thirring effect on two
      Earth satellites: it is 99 +/- 5 per cent of the value predicted by general
      relativity; the uncertainty of this measurement includes all known random and
      systematic errors, but we allow for a total +/- 10 per cent uncertainty to
      include underestimated and unknown sources of error.

PMID- 15496916
TI  - Poisson's ratio and the fragility of glass-forming liquids.
AB  - The nature of the transformation by which a supercooled liquid 'freezes' to a
      glass--the glass transition--is a central issue in condensed matter physics but
      also affects many other fields, including biology. Substantial progress has been
      made in understanding this phenomenon over the past two decades, yet many key
      questions remain. In particular, the factors that control the temperature
      dependent relaxation and viscous properties of the liquid phase as the glass
      transition is approached (that is, whether the glass-forming liquid is 'fragile'
      or 'strong') remain unclear. Here we show that the fragility of a glass-forming
      liquid is intimately linked to a very basic property of the corresponding glass
      phase: the relative strength of shear and bulk moduli, or Poisson's ratio.

PMID- 15496917
TI  - Low-voltage organic transistors with an amorphous molecular gate dielectric.
AB  - Organic thin film transistors (TFTs) are of interest for a variety of large-area
      electronic applications, such as displays, sensors and electronic barcodes. One
      of the key problems with existing organic TFTs is their large operating voltage,
      which often exceeds 20 V. This is due to poor capacitive coupling through
      relatively thick gate dielectric layers: these dielectrics are usually either
      inorganic oxides or nitrides, or insulating polymers, and are often thicker than
      100 nm to minimize gate leakage currents. Here we demonstrate a manufacturing
      process for TFTs with a 2.5-nm-thick molecular self-assembled monolayer (SAM)
      gate dielectric and a high-mobility organic semiconductor (pentacene). These TFTs
      operate with supply voltages of less than 2 V, yet have gate currents that are
      lower than those of advanced silicon field-effect transistors with SiO2
      dielectrics. These results should therefore increase the prospects of using
      organic TFTs in low-power applications (such as portable devices). Moreover,
      molecular SAMs may even be of interest for advanced silicon transistors where the
      continued reduction in dielectric thickness leads to ever greater gate leakage
      and power dissipation.

PMID- 15496918
TI  - Ultra-remote stereocontrol by conformational communication of information along a
      carbon chain.
AB  - Many receptors and allosteric proteins function through binding of a molecule to
      induce a conformational change, which then influences a remote active site. In
      synthetic systems, comparable intramolecular information transfer can be effected
      by using the shape of one part of a molecule to control the stereoselectivity of
      reactions occurring some distance away. However, the need for direct
      communication with the reaction site usually limits such remote stereocontrol to
      distances of not more than about five bond lengths. Cyclic structures overcome
      this problem by allowing the controlling centre and the reaction site to approach
      each other, but the information transfer spans only short absolute distances.
      Truly remote stereocontrol can, however, be achieved with rigid compounds
      containing amide groups: the conformation of the amides can be controlled by
      stereogenic centres and responds to that of neighbouring amide groups and in turn
      influences stereoselective reactions. This strategy has allowed remote
      stereocontrol spanning 8 (ref. 11) or 9 (ref. 12) bonds. Here we demonstrate
      stereocontrol over a reaction taking place more than 20 bond lengths from the
      controlling centre, corresponding to a linear distance of over 2.5 nm. This
      transmission of information, achieved by conformational changes relayed through
      the molecule, provides a chemical model of allostery and might serve as a
      molecular mechanism for communicating and processing information.

PMID- 15496919
TI  - Extreme climate of the global troposphere and stratosphere in 1940-42 related to
      El Nino.
AB  - Although the El Nino/Southern Oscillation phenomenon is the most prominent mode
      of climate variability and affects weather and climate in large parts of the
      world, its effects on Europe and the high-latitude stratosphere are
      controversial. Using historical observations and reconstruction techniques, we
      analyse the anomalous state of the troposphere and stratosphere in the Northern
      Hemisphere from 1940 to 1942 that occurred during a strong and long-lasting El
      Nino event. Exceptionally low surface temperatures in Europe and the north
      Pacific Ocean coincided with high temperatures in Alaska. In the lower
      stratosphere, our reconstructions show high temperatures over northern Eurasia
      and the north Pacific Ocean, and a weak polar vortex. In addition, there is
      observational evidence for frequent stratospheric warmings and high column ozone
      at Arctic and mid-latitude sites. We compare our historical data for the period
      1940-42 with more recent data and a 650-year climate model simulation. We
      conclude that the observed anomalies constitute a recurring extreme state of the
      global troposphere-stratosphere system in northern winter that is related to
      strong El Nino events.

PMID- 15496920
TI  - Release of gold-bearing fluids in convergent margin magmas prompted by magnetite
      crystallization.
AB  - A relationship between convergent margin magmas and copper-gold ore
      mineralization has long been recognized. The nature of the genetic link is
      controversial, particularly whether the link is due to high-oxygen-fugacity (fO2)
      melts and fluids released from subducted slabs or to brine exsolution during
      magmatic evolution. For submarine, subduction-related volcanic glasses from the
      eastern Manus basin, Papua New Guinea, we here report abrupt decreases in gold
      and copper abundances, coupled with a switch in the behaviour of titanium and
      iron from concentration increases to decreases as SiO2 rises. We propose that the
      abrupt depletion in gold and copper results from concurrent sulphur reduction as
      a result of fO2 buffering, causing enhanced formation of copper-gold
      hydrosulphide complexes that become scavenged from crystallizing melts into
      cogenetic magmatic aqueous fluids. This process is particularly efficient in
      oxidized arc magmas with substantial sulphate. We infer that subsequent migration
      and cooling of exsolved aqueous fluids create links between copper-gold
      mineralization and arc magmatism in the Manus basin, and at convergent margins in
      general.

PMID- 15496914
TI  - Genome duplication in the teleost fish Tetraodon nigroviridis reveals the early
      vertebrate proto-karyotype.
AB  - Tetraodon nigroviridis is a freshwater puffer fish with the smallest known
      vertebrate genome. Here, we report a draft genome sequence with long-range
      linkage and substantial anchoring to the 21 Tetraodon chromosomes. Genome
      analysis provides a greatly improved fish gene catalogue, including identifying
      key genes previously thought to be absent in fish. Comparison with other
      vertebrates and a urochordate indicates that fish proteins have diverged markedly
      faster than their mammalian homologues. Comparison with the human genome suggests
      approximately 900 previously unannotated human genes. Analysis of the Tetraodon
      and human genomes shows that whole-genome duplication occurred in the teleost
      fish lineage, subsequent to its divergence from mammals. The analysis also makes
      it possible to infer the basic structure of the ancestral bony vertebrate genome,
      which was composed of 12 chromosomes, and to reconstruct much of the evolutionary
      history of ancient and recent chromosome rearrangements leading to the modern
      human karyotype.

PMID- 15496921
TI  - A Silurian sea spider.
AB  - Pycnogonids (sea spiders) are marine arthropods numbering some 1,160 extant
      species. They are globally distributed in depths of up to 6,000 metres, and
      locally abundant; however, their typically delicate form and non-biomineralized
      cuticle has resulted in an extremely sparse fossil record that is not accepted
      universally. There are two opposing views of their phylogenetic position: either
      within Chelicerata as sister group to the euchelicerates, or as a sister taxon to
      all other euarthropods. The Silurian Herefordshire Konservat-Lagerstatte in
      England (approximately 425 million years (Myr) bp) yields exceptionally preserved
      three-dimensional fossils that provide unrivalled insights into the palaeobiology
      of a variety of invertebrates. The fossils are preserved as calcitic void in
      fills in carbonate concretions within a volcaniclastic horizon, and are
      reconstructed digitally. Here we describe a new pycnogonid from this deposit,
      which is the oldest adult sea spider by approximately 35 Myr and the most
      completely known fossil species. The large chelate first appendage is consistent
      with a chelicerate affinity for the pycnogonids. Cladistic analyses place the new
      species near the base of the pycnogonid crown group, implying that the latter had
      arisen by the Silurian period.

PMID- 15496922
TI  - Performance of maximum parsimony and likelihood phylogenetics when evolution is
      heterogeneous.
AB  - All inferences in comparative biology depend on accurate estimates of
      evolutionary relationships. Recent phylogenetic analyses have turned away from
      maximum parsimony towards the probabilistic techniques of maximum likelihood and
      bayesian Markov chain Monte Carlo (BMCMC). These probabilistic techniques
      represent a parametric approach to statistical phylogenetics, because their
      criterion for evaluating a topology--the probability of the data, given the tree-
      is calculated with reference to an explicit evolutionary model from which the
      data are assumed to be identically distributed. Maximum parsimony can be
      considered nonparametric, because trees are evaluated on the basis of a general
      metric--the minimum number of character state changes required to generate the
      data on a given tree--without assuming a specific distribution. The shift to
      parametric methods was spurred, in large part, by studies showing that although
      both approaches perform well most of the time, maximum parsimony is strongly
      biased towards recovering an incorrect tree under certain combinations of branch
      lengths, whereas maximum likelihood is not. All these evaluations simulated
      sequences by a largely homogeneous evolutionary process in which data are
      identically distributed. There is ample evidence, however, that real-world gene
      sequences evolve heterogeneously and are not identically distributed. Here we
      show that maximum likelihood and BMCMC can become strongly biased and
      statistically inconsistent when the rates at which sequence sites evolve change
      non-identically over time. Maximum parsimony performs substantially better than
      current parametric methods over a wide range of conditions tested, including
      moderate heterogeneity and phylogenetic problems not normally considered
      difficult.

PMID- 15496923
TI  - Ecological constraints on diversification in a model adaptive radiation.
AB  - Taxonomic diversification commonly occurs through adaptive radiation, the rapid
      evolution of a single lineage into a range of genotypes or species each adapted
      to a different ecological niche. Radiation size (measured as the number of new
      types) varies widely between phylogenetically distinct taxa and between replicate
      radiations within a single taxon where the ecological opportunities available
      seem to be identical. Here we show how variation in energy input (productivity)
      and environmental disturbance combine to determine the extent of diversification
      in a single radiating lineage of Pseudomonas fluorescens adapting to laboratory
      conditions. Diversity peaked at intermediate rates of both productivity and
      disturbance and declined towards the extremes in a manner reminiscent of well
      known ecological patterns. The mechanism responsible for the decrease in
      diversity arises from pleiotropic fitness costs associated with niche
      specialization, the effects of which are modulated by gradients of productivity
      and disturbance. Our results indicate that ecological gradients may constrain the
      size of adaptive radiations, even in the presence of the strong diversifying
      selection associated with ecological opportunity, by decoupling evolutionary
      diversification from ecological coexistence.

PMID- 15496924
TI  - Megabase deletions of gene deserts result in viable mice.
AB  - The functional importance of the roughly 98% of mammalian genomes not
      corresponding to protein coding sequences remains largely undetermined. Here we
      show that some large-scale deletions of the non-coding DNA referred to as gene
      deserts can be well tolerated by an organism. We deleted two large non-coding
      intervals, 1,511 kilobases and 845 kilobases in length, from the mouse genome.
      Viable mice homozygous for the deletions were generated and were
      indistinguishable from wild-type littermates with regard to morphology,
      reproductive fitness, growth, longevity and a variety of parameters assaying
      general homeostasis. Further detailed analysis of the expression of multiple
      genes bracketing the deletions revealed only minor expression differences in
      homozygous deletion and wild-type mice. Together, the two deleted segments
      harbour 1,243 non-coding sequences conserved between humans and rodents (more
      than 100 base pairs, 70% identity). Some of the deleted sequences might encode
      for functions unidentified in our screen; nonetheless, these studies further
      support the existence of potentially 'disposable DNA' in the genomes of mammals.

PMID- 15496925
TI  - Neural correlates of mental rehearsal in dorsal premotor cortex.
AB  - Behavioural and imaging studies suggest that when humans mentally rehearse a
      familiar action they execute some of the same neural operations used during overt
      motor performance. Similarly, neural activation is present during action
      observation in many of the same brain regions normally used for performance,
      including premotor cortex. Here we present behavioural evidence that monkeys also
      engage in mental rehearsal during the observation of sensory events associated
      with a well-learned motor task. Furthermore, most task-related neurons in dorsal
      premotor cortex exhibit the same activity patterns during observation as during
      performance, even during an instructed-delay period before any actual observed
      motion. This activity might be a single-neuron correlate of covert mental
      rehearsal.

PMID- 15496926
TI  - Regulation of oxidative stress by ATM is required for self-renewal of
      haematopoietic stem cells.
AB  - The 'ataxia telangiectasia mutated' (Atm) gene maintains genomic stability by
      activating a key cell-cycle checkpoint in response to DNA damage, telomeric
      instability or oxidative stress. Mutational inactivation of the gene causes an
      autosomal recessive disorder, ataxia-telangiectasia, characterized by
      immunodeficiency, progressive cerebellar ataxia, oculocutaneous telangiectasia,
      defective spermatogenesis, premature ageing and a high incidence of lymphoma.
      Here we show that ATM has an essential function in the reconstitutive capacity of
      haematopoietic stem cells (HSCs) but is not as important for the proliferation or
      differentiation of progenitors, in a telomere-independent manner. Atm-/- mice
      older than 24 weeks showed progressive bone marrow failure resulting from a
      defect in HSC function that was associated with elevated reactive oxygen species.
      Treatment with anti-oxidative agents restored the reconstitutive capacity of Atm
      /- HSCs, resulting in the prevention of bone marrow failure. Activation of the
      p16(INK4a)-retinoblastoma (Rb) gene product pathway in response to elevated
      reactive oxygen species led to the failure of Atm-/- HSCs. These results show
      that the self-renewal capacity of HSCs depends on ATM-mediated inhibition of
      oxidative stress.

PMID- 15496927
TI  - Essential role for the p110delta phosphoinositide 3-kinase in the allergic
      response.
AB  - Inflammatory substances released by mast cells induce and maintain the allergic
      response. Mast cell differentiation and activation are regulated, respectively,
      by stem cell factor (SCF; also known as Kit ligand) and by allergen in complex
      with allergen-specific immunoglobulin E (IgE). Activated SCF receptors and high
      affinity receptors for IgE (FcvarepsilonRI) engage phosphoinositide 3-kinases
      (PI(3)Ks) to generate intracellular lipid second messenger signals. Here, we
      report that genetic or pharmacological inactivation of the p110delta isoform of
      PI(3)K in mast cells leads to defective SCF-mediated in vitro proliferation,
      adhesion and migration, and to impaired allergen-IgE-induced degranulation and
      cytokine release. Inactivation of p110delta protects mice against anaphylactic
      allergic responses. These results identify p110delta as a new target for
      therapeutic intervention in allergy and mast-cell-related pathologies.

PMID- 15496930
TI  - Rewarding season.

PMID- 15496928
TI  - DNA end resection, homologous recombination and DNA damage checkpoint activation
      require CDK1.
AB  - A single double-strand break (DSB) induced by HO endonuclease triggers both
      repair by homologous recombination and activation of the Mec1-dependent DNA
      damage checkpoint in budding yeast. Here we report that DNA damage checkpoint
      activation by a DSB requires the cyclin-dependent kinase CDK1 (Cdc28) in budding
      yeast. CDK1 is also required for DSB-induced homologous recombination at any cell
      cycle stage. Inhibition of homologous recombination by using an analogue
      sensitive CDK1 protein results in a compensatory increase in non-homologous end
      joining. CDK1 is required for efficient 5' to 3' resection of DSB ends and for
      the recruitment of both the single-stranded DNA-binding complex, RPA, and the
      Rad51 recombination protein. In contrast, Mre11 protein, part of the MRX complex,
      accumulates at unresected DSB ends. CDK1 is not required when the DNA damage
      checkpoint is initiated by lesions that are processed by nucleotide excision
      repair. Maintenance of the DSB-induced checkpoint requires continuing CDK1
      activity that ensures continuing end resection. CDK1 is also important for a
      later step in homologous recombination, after strand invasion and before the
      initiation of new DNA synthesis.

PMID- 15496931
TI  - Boosting biotech in Finland.

PMID- 15496933
TI  - Recruiters and academia.

PMID- 15496935
TI  - Electroconvulsive seizures increase the expression of MAP kinase phosphatases in
      limbic regions of rat brain.
AB  - The mitogen-activated protein (MAP) kinase cascades regulate a variety of
      cellular activities, including cell growth, proliferation, and apoptosis, and are
      reported to play a role in the actions of antidepressant treatment. There are a
      number of different classes of protein phosphatases that could influence the MAP
      kinase cascade. One of these, the MAP kinase phosphatase (MKP) family, is known
      to play a key role in dephosphorylation of activated MAP kinase. In the present
      study, we analyzed the expression of the MKP1, MKP2, and MKP3 isoforms in rat
      brain after electroconvulsive seizure (ECS), considered the most effective
      treatment for depression. In situ hybridization analysis demonstrates that ECS
      differentially regulates the expression of the MKP isoforms. Expression of MKP1
      mRNA is robustly increased by acute ECS in the major cell layers of the
      hippocampus, including the dentate gyrus granule cell layer and the CA1 and CA3
      pyramidal cell layers. In contrast, MKP2 is induced mainly in the dentate gyrus
      and MKP3 is preferentially increased in the CA1 and CA3 cell layers. In the
      prefrontal cortex, all three MKP isoforms are upregulated by acute ECS
      administration. Chronic ECS resulted in a similar pattern of induction for each
      of the MKP subtypes, demonstrating that there is little or no desensitization of
      the response to repeated ECS. The induction of MKP expression serves as negative
      feedback control for the MAP kinase cascades. Upregulation of MKP expression
      could dampen the actions of ECS, indicating that blockade of the MKPs could
      enhance the actions of antidepressant treatment.

PMID- 15496936
TI  - Brief social defeat stress: long lasting effects on cocaine taking during a binge
      and zif268 mRNA expression in the amygdala and prefrontal cortex.
AB  - Social stress can engender behavioral and neural sensitization and this process
      appears to enhance the transition to compulsive drug abuse. Exposures to brief
      social defeat stress in rats have significant consequences on cocaine-reinforced
      behavior and on the level of functional activation within regions of the
      mesocorticolimbic dopamine system. The objectives of the current study were to
      examine the enduring consequences of brief episodes of social defeat stress on
      cocaine bingeing (during 24 h of continuous access) and on the emergence of
      neural adaptations as revealed by zif268 immediate early gene expression. Adult,
      male Long-Evans rats were subjected to four 25 min episodes of social defeat
      (once every 72 h). After 2 months, cocaine binges or zif268 mRNA gene expression
      were studied after confirming behavioral cross-sensitization to stimulant
      challenge. Sensitization to social defeat increased cocaine intake during a 24 h
      binge, effectively abolishing the typical circadian pattern of intake.
      Furthermore, 60 days after exposure to the sensitizing regimen of social defeat,
      levels of functional activation, measured by zif268 mRNA expression, in the
      central and medial amygdala were increased, while levels of activation in the
      medial prefrontal cortex were decreased. Persistent stress-induced levels of
      zif268 in the central and medial amygdala were attenuated by an injection of
      amphetamine (1.0 mg/kg). Divergent changes in zif268 within the amygdala and
      cortex 2 months after social defeat stress indicate the vulnerability of distinct
      cellular populations in networks that modulate the behavioral actions of
      psychomotor stimulants.

PMID- 15496937
TI  - Acetaldehyde enhances acquisition of nicotine self-administration in adolescent
      rats.
AB  - Tobacco use has one of the highest rates of addiction and relapse of any abused
      drug. Paradoxically, however, in animal models of reinforcement nicotine appears
      weak compared to other abused drugs. We report here that acetaldehyde, a major
      component of tobacco smoke, enhances nicotine self-administration. Juvenile and
      adult male rats were implanted with intravenous catheters and tested for self
      administration 4 days later at postnatal day 27 or 90, respectively. Animals were
      tested, without prior response training, in five daily 3-h sessions where each
      nose-poke delivered an intravenous injection followed by a 60-s timeout. Animals
      (11-13/group) were offered one of the following solutions: nicotine (30
      microg/kg/injection), acetaldehyde (16 microg/kg/inj), nicotine (30
      microg/kg/inj)+acetaldehyde (16 microg/kg/inj), or saline. The youngest animals
      responded significantly more for nic+acet than for saline or for either drug
      alone. Responding at the reinforced hole was significantly higher than at the
      nonreinforced hole or at the reinforced hole during noncontingent injections of
      nic+acet. Tests with receptor antagonists indicated that these drug effects are
      mediated by central, but not peripheral, nicotinic receptors. There was an age
      related decline in self-administration of nic+acet, but not for cocaine. Taken
      together, these results indicate that acetaldehyde, at the low concentrations
      found in tobacco smoke, interacts with nicotine to increase responding in a
      stringent self-administration acquisition test where nicotine alone is only
      weakly reinforcing, and that adolescent animals are more sensitive to these
      actions than adults. Animal models of tobacco addiction could be improved by
      combining acetaldehyde, and possibly other smoke components, with nicotine to
      more accurately reflect the pharmacological profile of tobacco smoke.

PMID- 15496938
TI  - N-substituted piperazines abused by humans mimic the molecular mechanism of 3,4
      methylenedioxymethamphetamine (MDMA, or 'Ecstasy').
AB  - 3,4-Methylenedioxymethamphetamine (MDMA, or 'Ecstasy') is an illicit drug that
      stimulates the release of serotonin (5-HT) and dopamine (DA) from neurons. Recent
      evidence reveals that drug users are ingesting piperazine analogs, like 1
      benzylpiperazine (BZP, or 'A2') and 1-(m-trifluoromethylphenyl)piperazine (TFMPP,
      or 'Molly'), to mimic psychoactive effects of MDMA. In the present study, we
      compared the neurochemistry of MDMA, BZP, and TFMPP in rats. The effects of MDMA,
      BZP, and TFMPP on transporter-mediated efflux of [3H]5-HT and [3H]MPP+ (DA
      transporter substrate) were determined in synaptosomes. The effects of drugs on
      extracellular levels of 5-HT and DA were examined using in vivo microdialysis in
      conscious rats. MDMA evoked transporter-mediated release of [3H]5-HT and
      [3H]MPP+. BZP released [3H]MPP+, whereas TFMPP was a selective releaser of [3H]5
      HT. MDMA (1-3 mg/kg, i.v.) increased dialysate 5-HT and DA in a dose-related
      fashion, with actions on 5-HT being predominant. BZP (3-10 mg/kg, i.v.) elevated
      dialysate DA and 5-HT, while TFMPP (3-10 mg/kg, i.v.) elevated 5-HT.
      Administration of BZP plus TFMPP at a 1:1 ratio (BZP/TFMPP) produced parallel
      increases in dialysate 5-HT and DA; a 3 mg/kg dose of BZP/TFMPP mirrored the
      effects of MDMA. At a 10 mg/kg dose, BZP/TFMPP increased dialysate DA more than
      the summed effects of each drug alone, and some rats developed seizures. Our
      results show that BZP/TFMPP and MDMA share the ability to evoke monoamine
      release, but dangerous drug-drug synergism may occur when piperazines are
      coadministered at high doses.

PMID- 15496939
TI  - Prolonged nicotine administration results in biphasic, brain-specific changes in
      kynurenate levels in the rat.
AB  - The content of the endogenous NMDA and alpha7 nicotinic acetylcholine receptor
      antagonist kynurenate (KYNA) is increased in the cerebral cortex and
      cerebrospinal fluid of patients with schizophrenia. In view of the very high
      incidence of smoking in schizophrenic individuals, a study was designed to
      examine the effect of acute and prolonged nicotine administration on brain KYNA
      levels in experimental animals. Adult male rats received subcutaneous nicotine
      injections twice daily for up to 10 days, and animals were routinely killed 1 h
      after the last injection. Neither acute treatment nor a 2-day regimen with 1
      mg/kg nicotine (= 0.35 mg/kg pure base) caused changes in cerebral KYNA levels.
      Four- or 6 day-treatment with this dose resulted in 20-40% decreases in cerebral
      KYNA content. Animals treated with 1 or 10 mg/kg nicotine for 10 days showed dose
      dependent, significant increases in KYNA in hippocampus, striatum, and cortex,
      but not in the serum. Discontinuation of nicotine treatment for 7 days restored
      brain KYNA to control levels. Separate animals, implanted with osmotic minipumps
      delivering 2 mg/kg of nicotine/day for 10 days also showed significant elevations
      in brain KYNA. Hippocampal microdialysis, performed in animals receiving nicotine
      (1 mg/kg) for 10 days, revealed a significant increase in basal extracellular
      KYNA levels compared to controls, whereas acute treatment with this dose produced
      no such change. Measurements of KYNA's bioprecursor kynurenine in brain or blood
      did not reveal any nicotine-induced changes. These results indicate that nicotine
      has a brain-specific, biphasic effect on the transamination of kynurenine to
      KYNA. Such nicotine-induced fluctuations in brain KYNA may cause functional
      changes in processes that regulate glutamatergic and cholinergic
      neurotransmission in the normal and diseased brain.

PMID- 15496940
TI  - Nicotine therapy in adulthood reverses the synaptic and behavioral deficits
      elicited by prenatal exposure to phenobarbital.
AB  - A major objective in identifying the mechanisms underlying neurobehavioral
      teratogenicity is the possibility of designing therapies that reverse or offset
      drug- or toxicant-induced neural damage. In our previous studies, we identified
      deficits in hippocampal muscarinic cholinergic receptor-induced membrane
      translocation of protein kinase C (PKC)gamma as the likely mechanism responsible
      for adverse behavioral effects of prenatal phenobarbital exposure. We therefore
      explored whether behavioral and synaptic defects could be reversed in adulthood
      by nicotine administration. Pregnant mice were given milled food containing
      phenobarbital to achieve a daily dose of 0.5-0.6 g/kg from gestational days 9-18.
      In adulthood, offspring showed deficits in the Morris maze, a behavior dependent
      on the integrity of septohippocampal cholinergic synaptic function, along with
      the loss of the PKCgamma response. Phenobarbital-exposed and control mice then
      received nicotine (10 mg/kg/day) for 14 days via osmotic minipumps. Nicotine
      reversed the behavioral deficits and restored the normal response of hippocampal
      PKCgamma to cholinergic receptor stimulation. The effects were regionally
      specific, as PKCgamma in the cerebellum was unaffected by either phenobarbital or
      nicotine; furthermore, in the hippocampus, PKC isoforms unrelated to the
      behavioral deficits showed no changes. Nicotine administration thus offers a
      potential therapy for reversing neurobehavioral deficits originating in
      septohippocampal cholinergic defects elicited by prenatal drug or toxicant
      exposures.

PMID- 15496941
TI  - Biphasic effects of adrenal steroids on learned helplessness behavior induced by
      inescapable shock.
AB  - Corticosterone (CS) has been shown to regulate behavior in the learned
      helplessness (LH) paradigm. Here we provide evidence for a U-shaped relationship
      between the increasing doses of CS administered and escape failures in the LH
      model. Replacement with CS (20-400 microg/ml in drinking water) in
      adrenalectomized (ADX) animals was utilized to examine how the selective
      activation of mineralocorticoid (MR) and glucocorticoid (GR) receptors is related
      to the behavioral impairments induced by inescapable shock (IS). Available MR and
      GR levels were determined in hippocampal cytosol by radioligand binding assays.
      Non-CS replaced ADX animals showed a high percentage of escape failures assessed
      48 h after IS. A CS does of 100 microg/ml given to ADX animals markedly reduced
      escape failures and resulted in an almost total reduction of available MR
      associated with a partial reduction of GR. However, the administration of
      aldosterone (ALDO), a selective MR agonist, was not sufficient to restore normal
      coping behavior. Moreover, an important role for GR was further shown by means of
      the specific GR antagonist, RU 38486, which blocked the reduction of LH in ADX
      rats that were given 100 microg/ml CS. Higher doses of CS given to ADX rats
      reinstated the LH behavior, and SHAM rats that produced stress CS levels also
      produced LH behavior. The results indicate a U-shaped dose response function with
      both negligible and high CS levels being associated with LH behavior. Hence,
      along with a moderate reduction of available GR level in the cytosol, a large
      decrease in MR availability seems to be necessary to prevent the acquisition and
      expression of LH. However, very high reduction of available GR is associated with
      LH behavior.

PMID- 15496942
TI  - Generics for AIDS.

PMID- 15496943
TI  - Mucosal dendritic cells in immunity and inflammation.

PMID- 15496944
TI  - A license to remember.

PMID- 15496945
TI  - Inside sensors detecting outside pathogens.

PMID- 15496946
TI  - Class switching and Myc translocation: how does DNA break?

PMID- 15496947
TI  - CD28-B7 bidirectional signaling: a two-way street to activation.

PMID- 15496948
TI  - Are dendritic cells end cells?

PMID- 15496950
TI  - Intrinsic immunity: a front-line defense against viral attack.
AB  - In addition to the conventional innate and acquired immune responses, complex
      organisms have evolved an array of dominant, constitutively expressed genes that
      suppress or prevent viral infections. Two major cellular defenses against
      infection by retroviruses are the Fv1 and TRIM5 class of inhibitors that target
      incoming retroviral capsids and the APOBEC3 class of cytidine deaminases that
      hypermutate and destabilize retroviral genomes. Additional, less well
      characterized activities also inhibit viral replication. Here, the present
      understanding of these 'intrinsic' immune mechanisms is reviewed and their role
      in protection from retroviral infection is discussed.

PMID- 15496954
TI  - Combined haplotype analysis of the interleukin-19 and -20 genes: relationship to
      plaque-type psoriasis.
AB  - There is increasing evidence to suggest that the newly discovered cytokines
      interleukin (IL)-19 and -20 have a role in the function of epidermis and in
      psoriasis. The genes encoding these cytokines locate into the genomic IL-10
      region on human chromosome 1. The aim of the present study was to analyze whether
      single-nucleotide polymorphisms (SNPs) in these genes have an impact on the
      susceptibility for psoriasis. From pairwise linkage disequilibrium (LD) matrix of
      the IL-19 and -20 gene polymorphisms, what reflects the nonrandom association of
      alleles at these markers, it was apparent that IL-19 and -20 genes form one block
      of LD. We found that the HT3 CACCGGAA haplotype of the IL-19 and -20 genes was
      associated with an increased risk of psoriasis, reflecting its role in
      determining susceptibility to plaque-type psoriasis. Although association
      analysis of the IL-19 gene indicated that minor alleles of the IL-19 gene SNPs
      (rs2243188, rs2243169 and rs2243158) revealed protective effect to psoriasis and
      haplotype analysis of the IL-19 gene proved significant protective effect of the
      TGATA haplotype in case of late-onset disease, combined haplotype analysis of the
      IL-19 and -20 genes demonstrated that protective effect of the IL-19 gene is
      secondary to the susceptibility effect of the IL-20 gene.

PMID- 15496956
TI  - T-cell engineering by a chimeric T-cell receptor with antibody-type specificity
      for the HIV-1 gp120.
AB  - Immune-based approaches of cell therapy against viral pathogens such as the human
      immunodeficiency virus type 1 (HIV-1) could be of primary importance for the
      control of this viral infection. Here, we designed a chimeric cell surface
      receptor (105TCR) to provide primary human T-lymphocytes with antibody-type
      specificity for the HIV-1 envelope glycoprotein. This receptor includes the
      single chain Fv domain of the neutralizing anti-gp120 human monoclonal antibody
      F105, CD8alpha hinge and the transmembrane and the cytoplasmic domains of
      TCRzeta. Our results show that 105TCR is expressed at the cellular surface and is
      capable of recognizing the HIV-1 envelope glycoprotein inducing highly efficient
      effector T-cell responses, including extracellular signal-regulated kinase
      phosphorylation and cytokine secretion. Moreover, human primary CD8+ T
      lymphocytes transduced by oncoretroviral and lentiviral vectors containing the
      105TCR gene are able to mediate in vitro-specific cytolysis of envelope
      expressing cells and HIV-1-infected CD4+ T-lymphocytes. These findings suggest
      that 105TCR is particularly suited for in vivo efficacy studies.

PMID- 15496955
TI  - DNA microarray allows molecular profiling of rheumatoid arthritis and
      identification of pathophysiological targets.
AB  - This study was undertaken to evaluate the possibility to obtain a molecular
      signature of rheumatoid arthritis (RA) comparatively osteoarthritis (OA), and to
      lay the bases to develop new diagnostic tools and identify new targets.
      Microarray technology was used for such an analysis. The gene expression profiles
      of synovial tissues from patients with confirmed RA, and patients with OA were
      established and compared. A set of 63 genes was selected, based, more
      specifically, on their overexpression or underexpression in RA samples compared
      to OA. Results for six of these genes have been verified by quantitative PCR
      using both samples identical to those used in the microarray experiments and
      entirely separate samples. Expression profile of the 48 known genes allowed the
      correct classification of additional RA and OA patients. Furthermore, the
      distinct expression of three of the selected genes was also studied by
      quantitative RT-PCR in cultured synovial cells. Detailed analysis of the
      expression profile of the selected genes provided evidence for dysregulated
      biological pathways, pointed out to chromosomal location and revealed novel genes
      potentially involved in RA. It is proposed that such an approach allows valuable
      diagnosis/prognostics tools in RA to be established and potential targets for
      combating the disease to be identified.

PMID- 15496957
TI  - Gene therapy progress and prospects: gene therapy for diabetes mellitus.
AB  - Diabetes mellitus has long been targeted, as yet unsuccessfully, as being curable
      with gene therapy. The main hurdles have not only been vector-related toxicity
      but also the lack of physiological regulation of the expressed insulin. Recent
      advances in understanding the developmental biology of beta-cells and the
      transcriptional cascade that drives it have enabled both in vivo and ex vivo gene
      therapy combined with cell therapy to be used in animal models of diabetes with
      success. The associated developments in the stem cell biology and immunology have
      opened up further opportunities for gene therapy to be applied to target
      autoimmune diabetes.

PMID- 15496958
TI  - Retroviral vector backbone immunogenicity: identification of cytotoxic T-cell
      epitopes in retroviral vector-packaging sequences.
AB  - Retroviral vectors are the frequently applied gene delivery vehicles for clinical
      gene therapy, but specificity of the immunogenicity to the protein encoded by the
      inserted gene of interest is a problem which needs to be overcome. Here, we
      describe human cytotoxic T-lymphocyte (CTL) clones recognizing epitopes derived
      from the protein encoded by the retroviral vector backbone, which were
      established during the course of our attempts to generate CTLs against
      cytomegalovirus (CMV) or human papilloma virus (HPV) in vitro. In the case of
      healthy CMV-seronegative donors, CTL lines specific for retrovirally transduced
      cells were generated in four out of eight donors by stimulating CD8 T cells with
      CD40-activated B (CD40-B) cells retrovirally transduced with CMV-pp65. Two CTL
      clones derived from one of the CTL lines were found to recognize epitopes from
      gag in the context of HLA-B(*)4403 and -B(*)4601, respectively. Similarly, an HLA
      B(*)3501-restricted CTL clone from a cervical cancer patient recognized an
      epitope located in the junctional regions of the gag and pol sequences. These
      results show that polypeptides encoded by components of the retroviral vector
      backbone are in fact immunogenic, generating CTLs in vitro in human cells. Thus,
      potential CTL responses to retroviral products should also be considered in
      clinical settings.

PMID- 15496959
TI  - Adenoviral clostridial light chain gene-based synaptic inhibition through
      neuronal synaptobrevin elimination.
AB  - Clostridial neurotoxins have assumed increasing importance in clinical
      application. The toxin's light chain component (LC) inhibits synaptic
      transmission by digesting vesicle-docking proteins without directly altering
      neuronal health. To study the properties of LC gene expression in the nervous
      system, an adenoviral vector containing the LC of tetanus toxin (AdLC) was
      constructed. LC expressed in differentiated neuronal PC12 cells was shown to
      induce time- and concentration-dependent digestion of mouse brain synaptobrevin
      in vitro as compared to control transgene products. LC gene expression in the rat
      lumbar spinal cord disrupted hindlimb sensorimotor function in comparison to
      control vectors as measured by the Basso-Beattie-Bresnahan (BBB) scale (P<0.001)
      and rotarod assay (P<0.003). Evoked electromyography (EMG) showed increased
      stimulus threshold and decreased response current amplitude in LC gene
      transferred rats. At the peak of functional impairment, neither neuronal TUNEL
      staining nor reduced motor neuron density could be detected. Spontaneous
      functional recovery was observed to parallel the cessation of LC gene expression.
      These results suggest that light chain gene delivery within the nervous system
      may provide a nondestructive means for focused neural inhibition to treat a
      variety of disorders related to excessive synaptic activity, and prove useful for
      the study of neural circuitry.

PMID- 15496960
TI  - Ribozyme targeting of the growth factor pleiotrophin in established tumors: a
      gene therapy approach.
AB  - The growth and metastasis of solid tumors relies on the activities of polypeptide
      growth factors to recruit stromal tissue and expand the tumor mass. Pleiotrophin
      (PTN) is a secreted growth factor with angiogenic activity that has been found to
      contribute to the growth and metastasis of tumors including melanoma. Here, we
      present a gene therapy approach of targeting PTN in established tumors using
      ribozymes. Tetracycline-regulated ribozyme expression vectors were used to
      deplete conditionally PTN mRNA from melanoma xenograft tumors in vivo. We found
      that tetracycline-mediated initiation of ribozyme expression in established
      tumors reduced further tumor growth. Next, we generated synthetic anti-PTN
      ribozymes that inhibit PTN-dependent colony formation of cells in soft agar.
      Intraperitoneal administration of these synthetic ribozymes into nude mice
      inhibited growth of PTN-positive, subcutaneous melanoma. Furthermore, PTN
      released from the tumors into the circulation of mice was reduced after ribozyme
      treatment. These data show that ribozyme targeting of rate-limiting tumor growth
      factors could provide an efficient tool for cancer therapy and that the efficacy
      may be reflected in the reduction of the serum levels of the targeted protein,
      PTN.

PMID- 15496961
TI  - Redirecting human CD4+ T lymphocytes to the MHC class I-restricted melanoma
      antigen MAGE-A1 by TCR alphabeta gene transfer requires CD8alpha.
AB  - Adoptive immunotherapy involving the transfer of autologous tumor or virus
      reactive T lymphocytes has demonstrated its effectiveness in the eradication of
      cancer and virally infected cells. Clinical trails and in vitro studies have
      focused on CD8+ cytotoxic T-cell receptor (TCR) alphabeta lymphocytes since these
      cells directly kill virally infected- and tumor cells after antigen-specific
      recognition via their TCR alphabeta. However, increasing evidence suggests that
      induction of sustained immunity against cancer and viral infections depends on
      the presence of tumor- or virus-specific CD4+ T lymphocytes, which are restricted
      by MHC class II. Here, we show that these MHC class II-restricted CD4+ T
      lymphocytes can efficiently be redirected to MHC class I-restricted tumor cells
      by retroviral introduction of an HLA-A1/MAGE-A1-specific chimeric two-chain TCR
      ValphaCalphazeta/VbetaCbetazeta (tcTCR/zeta). However, TCR-transduced CD4+ T
      lymphocytes were only able to specifically bind to HLA-A1/MAGE-A1 complexes and
      respond to HLA-A1+/MAGE-A1+ melanoma cells when the CD8alpha gene was
      cointroduced. These CD4+/CD8alpha+/TCR(POS) T lymphocytes produce IFN-gamma,
      TNFalpha and IL-2 when specifically stimulated via the introduced TCR with
      immobilized HLA-A1/MAGE-A1 complexes or HLA-A1+/MAGE-A1+ melanoma cells.
      Furthermore, introduction of the CD8alpha gene into TCR(POS) T lymphocytes
      rendered these T lymphocytes cytotoxic for HLA-A1+/MAGE-A1+ melanoma cells. These
      results demonstrate that human CD4+ T lymphocytes when genetically grafted with
      an HLA-A1/MAGE-A1-specific TCR and CD8alpha are induced to kill and produce
      cytokines upon specific interaction with the relevant melanoma cells. Hence, CD4+
      T lymphocytes, in addition to CD8+ T lymphocytes, may be critical effector cells
      for adoptive immuno-gene therapy to generate a sustained tumor-specific immune
      response in cancer patients.

PMID- 15496962
TI  - siRNA therapeutics: big potential from small RNAs.
AB  - RNA interference (RNAi) is now an umbrella term referring to post-transcriptional
      gene silencing mediated by either degradation or translation arrest of target
      RNA. This process is initiated by double-stranded RNA with sequence homology
      driving specificity. The discovery that 21-23 nucleotide RNA duplexes (small
      interfering RNAs, siRNAs) mediate RNAi in mammalian cells opened the door to the
      therapeutic use of siRNAs. While much work remains to optimize delivery and
      maintain specificity, the therapeutic advantages of siRNAs for treatment of viral
      infection, dominant disorders, cancer, and neurological disorders show great
      promise.

PMID- 15496963
TI  - Adeno-associated virus vector-mediated interleukin-10 gene transfer inhibits
      atherosclerosis in apolipoprotein E-deficient mice.
AB  - Inflammation is a major contributor to atherosclerosis by its effects on arterial
      wall biology and lipoprotein metabolism. Interleukin-10 (IL-10) is an anti
      inflammatory cytokine that may modulate the atherosclerotic disease process. We
      investigated the effects of adeno-associated virus (AAV) vector-mediated gene
      transfer of IL-10 on atherogenesis in apolipoprotein E (ApoE)-deficient mice. A
      murine myoblast cell line, C2C12, transduced with AAV encoding murine IL-10 (AAV2
      mIL10) secreted substantial amounts of IL-10 into conditioned medium. The
      production of monocyte chemoattractant protein-1 (MCP-1) by the murine macrophage
      cell line, J774, was significantly inhibited by conditioned medium from AAV2
      mIL10-transduced C2C12 cells. ApoE-deficient mice were injected with AAV5-mIL10
      into their anterior tibial muscle at 8 weeks of age. The expression of MCP-1 in
      the vascular wall of the ascending aorta and serum MCP-1 concentration were
      decreased in AAV5-mIL10-transduced mice compared with AAV5-LacZ-transduced mice.
      Oil red-O staining of the ascending aorta revealed that IL-10 gene transfer
      resulted in a 31% reduction in plaque surface area. Serum cholesterol
      concentrations were also significantly reduced in AAV5-mIL10-transduced mice. To
      understand the cholesterol-lowering mechanism of IL-10, we measured the cellular
      cholesterol level in HepG2 cells, resulting in its significant decrease by the
      addition of IL-10 in a dose-dependent manner. Furthermore, IL-10 suppressed HMG
      CoA reductase expression in the HepG2 cells. These observations suggest that
      intramuscular injection of AAV5-mIL10 into ApoE-deficient mice inhibits
      atherogenesis through anti-inflammatory and cholesterol-lowering effects.

PMID- 15496964
TI  - Combining high selectivity of replication with fiber chimerism for effective
      adenoviral oncolysis of CAR-negative melanoma cells.
AB  - Oncolytic adenoviruses constitute a new and promising tool for cancer treatment
      that has been rapidly translated into clinical trials. However, minimal or absent
      expression of the adenovirus serotype 5 (Ad5) receptor CAR (coxsackievirus and
      adenovirus receptor) on cancer cells represents a major limitation for Ad5-based
      oncolysis. Here, we report on the resistance of CAR-negative primary melanoma
      cells to cell killing by wild-type Ad5 (Ad5wt) even after high titer infection,
      thus underlining the need for tropism-modification of oncolytic adenoviruses. We
      engineered a new generation of oncolytic adenoviruses that exhibit both efficient
      target cell infection by swapping Ad5 fiber domains with those of Ad serotype 3,
      which binds to a receptor distinct from CAR, and targeted virus replication.
      Fiber chimerism resulted in efficient cytopathicity to primary melanoma cells,
      which was at least 10(4)-fold increased relative to Ad5wt. Since viral
      infectivity mediated by such modified viral capsids was not cell type-specific,
      it was pivotal to carefully restrict adenoviral replication to target cells.
      Towards this end, we replaced both E1A and E4 promoters of fiber chimeric viruses
      by tyrosinase enhancer/promoter constructs. The resulting viruses showed melanoma
      specific expression of E1A and E4 and combined efficient virus replication and
      cell killing in melanoma cell lines and primary melanoma cells with a remarkable
      specificity profile that implements strong attenuation in nonmelanoma cells,
      including normal fibroblasts and keratinocytes.

PMID- 15496965
TI  - What factors are associated with high plasma B-type natriuretic peptide levels in
      a general Japanese population?
AB  - There are few community-based epidemiologic studies that have dealt with risk
      factors for heart failure in non-Western populations. It has been reported that
      the measurement of plasma B-type natriuretic peptide (BNP) is useful for
      detecting patients with asymptomatic heart failure. To clarify the determinants
      of high plasma BNP level, the association of BNP with cardiovascular risk factors
      in community dwelling residents was examined. The plasma BNP levels were measured
      in 686 residents aged 35-69 years who received annual health check-up. The
      relationship of BNP to blood pressure, blood haemoglobin, serum cholesterol
      (total and high-density lipoprotein cholesterol), plasma glucose,
      electrocardiographic (ECG) findings, urinary salt excretion, and lifestyle
      factors (smoking and alcohol consumption) were cross-sectionally analysed. The
      plasma BNP geometric mean was 13.7 pg/ml. Both linear and logistic regression
      analyses indicated that the plasma BNP levels were positively associated with
      age, urinary salt excretion, higher blood pressure, high R-wave voltage in the 12
      lead ECG (Minnesota Code 3-1 or 3-3), and female gender. Plasma BNP levels were
      inversely associated with blood haemoglobin levels. Gender-specific analysis
      showed similar results. However, plasma BNP did not correlate with other
      cardiovascular risk factors such as serum lipids.

PMID- 15496966
TI  - The coming epidemic: hypertension in rural Kyrgyzstan, Central Asia.
AB  - Eastern Europe is experiencing an epidemic of cardiovascular disease far
      outpacing rates in Western Europe. This epidemic was heralded by a precipitous
      rise in hypertension prevalence. The former Soviet states of Central Asia may be
      facing a similar epidemic. In order to access this threat, we performed a
      retrospective analysis of data generated during humanitarian medical visits to
      two villages in Kyrgyzstan, Central Asia. The age-adjusted prevalence of
      hypertension was 39%. Hypertension was much more common among men than women (46
      vs 33%, respectively). In addition, the rise in blood pressure with age was
      striking, surpassing the experience in Western countries. This epidemic of
      hypertension may herald a coming epidemic of cardiovascular disease in Central
      Asia.

PMID- 15496967
TI  - Acute effects of inhaled nitric oxide on pulmonary and cardiac function in
      preterm infants with evolving bronchopulmonary dysplasia.
AB  - BACKGROUND: Inhaled nitric oxide (iNO) reduces pulmonary vascular resistance by
      preferential vasodilation in ventilated lung units. In experimental animals, iNO
      also reduces airway resistance by smooth muscle relaxation. Hence, there may be a
      therapeutic role for iNO in evolving bronchopulmonary dysplasia (BPD). OBJECTIVE:
      To evaluate the acute effects of low-dose iNO on lung mechanics, ventilation
      distribution, oxygenation, and cardiac function in preterm infants with evolving
      BPD. METHODS: Measurements of lung compliance (C(L)), airway resistance (R(L)),
      ventilation-distribution (N(2) clearance in multiple-breath washout), oxygenation
      (SpO(2)), left ventricular ejection fraction (LVEF) and right ventricular
      shortening fraction were obtained before and during 2 hours of iNO (10 ppm) in a
      group of ventilated preterm infants with evolving BPD. RESULTS: A total of 13
      preterm infants with (mean+/-SD) BW: 663.8+/-116 g, GA: 24.9+/-1.2 weeks, age:
      32+/-14 days, mean airway pressure: 6.7+/-0.9 cmH(2)O and fraction of inspired
      oxygen: 0.35+/-0.06 were studied. iNO did not affect C(L), R(L) or N(2)
      clearance. There was a small increase in LVEF. Mean SpO(2) remained unchanged,
      but the duration of spontaneous hypoxemic episodes increased during iNO.
      CONCLUSION: Low-dose iNO had no acute effects on lung function, cardiac function
      and oxygenation in evolving BPD.

PMID- 15496969
TI  - Effect of managed care on perinatal transports for the publicly funded in upstate
      New York.
AB  - OBJECTIVE: To determine if Medicaid Managed Care (MMC) status influences
      perinatal transfer rates among publicly funded individuals in a well-regionalized
      area. STUDY DESIGN: Perinatal transport rates were determined from deidentified
      data from the NYS Perinatal Data System (PDS). The predictor of interest was
      managed care status. Covariates included maternal, newborn, and regional
      variables. RESULTS: The unadjusted probability of maternal transfer was 28% lower
      among women enrolled in MMC vs those with Medicaid Fee-for-Service (MFFS) (odds
      ratio (OR)=0.72; 95% confidence interval (CI): 0.63 to 0.82). When adjusted for
      clinical variables influencing maternal transfer and hospital level, women in
      managed care were 44% less likely to be transferred (OR=0.56; 95% CI: 0.36 to
      0.86). Newborns were transferred at similar rates regardless of managed care
      status. CONCLUSIONS: MMC status remains a significant independent predictor for
      maternal transfer in upstate New York (NY). Despite a well-regionalized
      organization for perinatal care where pre-existing written protocols for transfer
      between institutions are established independent of insurance status, managed
      care may influence decisions on nature and location of care delivery.

PMID- 15496968
TI  - Mortality risk associated with perinatal drug and alcohol use in California.
AB  - OBJECTIVE: To analyze the relationship between perinatal drug/alcohol use and
      maternal, fetal, neonatal, and postneonatal mortality. STUDY DESIGN: Linked
      California discharge, birth and death certificate data from 1991-1998 were used
      to identify drug/alcohol-diagnosed births. Mortality relative risk (RR) ratios
      were calculated and logistic models were generated for mortality outcomes.
      RESULTS: Among 4,536,701 birth records, 1.20% contained drug/alcohol discharge
      diagnostic codes (n=54,290). The unadjusted RRs for maternal (RR=2.7), fetal
      (RR=1.3), neonatal (RR=2.4), and postneonatal (RR=4.3) mortality were increased
      for drug/alcohol-diagnosed births. After controlling for potential confounding,
      the odds of maternal death for cocaine use (OR=2.15) remained significant as did
      amphetamine (OR=1.77), cocaine (OR=1.43), polydrug (OR=2.01) and other
      drug/alcohol use (OR=1.79) for postneonatal mortality. CONCLUSIONS: The
      association of cocaine use with maternal mortality and any drug/alcohol use with
      postneonatal mortality supports screening and identifying women using illicit
      drugs and alcohol during pregnancy. Increased collaboration with drug treatment
      programs and closer follow-up for drug-using women and their children may improve
      mortality outcomes.

PMID- 15496970
TI  - A new translocation t(9;11)(q34;p15) fuses NUP98 to a novel homeobox partner
      gene, PRRX2, in a therapy-related acute myeloid leukemia.

PMID- 15496971
TI  - Immune recovery after low-dose Campath therapy in a group of pretreated patients
      affected by B-cell chronic lymphocytic leukemia.

PMID- 15496972
TI  - Inhibition of PI3K, mTOR and MEK signaling pathways promotes rapid apoptosis in B
      lineage ALL in the presence of stromal cell support.
AB  - Bone marrow stromal cells are essential for the differentiation, survival and
      proliferation of normal and leukemic human B-lineage cells. Leukemic cells
      require stromal cell support for optimal proliferation and apoptotic resistance.
      Stromal cell contact can promote resistance to chemotherapeutic agents. In this
      study, we have made use of small molecular weight inhibitors and an established
      stromal cell-dependent pre-B-ALL cell line, BLIN-2, to investigate the role of
      the MAP kinase, PI3K/Akt, JAK/STAT and mTOR pathways in the promotion of leukemic
      cell growth in the presence of stromal cell support. Treatment with PI3K+JAK,
      PI3K+MEK, or MEK+JAK inhibitor combinations resulted in an inhibition of
      proliferation as measured by DNA synthesis. However, only inhibition of both PI3K
      and MEK or both mTOR and MEK resulted in a dramatic increase in the number of
      annexinV(+)/PI(+) apoptotic events within a 24 h period. Our data suggest that
      stromal cell-mediated apoptotic protection in B-lineage ALL is mediated by
      PI3K/mTOR and MEK via a synergistic mechanism(s).

PMID- 15496973
TI  - Overexpression of HOXB4 confers a myelo-erythroid differentiation delay in vitro.

PMID- 15496974
TI  - Immunosurveillance of childhood ALL: polymorphic interferon-gamma alleles are
      associated with age at diagnosis and clinical risk groups.
AB  - Interferon-gamma (IFN-gamma) has been implicated as an important mediator of
      antitumor immunity in murine model systems. To determine whether a CA-repeat
      associated with differential NFkappaB-binding and IFN-gamma-expression levels may
      influence the incidence, manifestation and early clinical treatment response of
      childhood acute lymphoblastic leukemia, we performed PCR-based genotyping of 393
      patients with ALL and 207 healthy controls. We could not find any differences in
      the allele distribution comparing patients and controls. However, when we further
      analyzed the allele frequencies with respect to age of clinical manifestation, we
      found that patients with B-lineage ALL showing the IFN-gamma high-expressing
      genotype presented at a more advanced age compared to those patients with
      intermediate and low-expressing genotypes (median 6 vs 4.4 years, P=0.01).
      Furthermore, we found a significantly higher number of low expressors in the
      group of high-risk patients (HR n=32 and MR/SR n=266, P=0.025, defined by
      prednisone response, cytological remission and minimal residual disease (MRD))
      with B-lineage ALL. Thus, we provide evidence that polymorphic IFN-gamma alleles
      are associated with age at clinical presentation and risk groups such as
      prednisone response in B-lineage ALL, suggesting distinct effects of IFN-gamma in
      immunosurveillance and early response to steroid therapy.

PMID- 15496975
TI  - KIAA1509 is a novel PDGFRB fusion partner in imatinib-responsive
      myeloproliferative disease associated with a t(5;14)(q33;q32).
AB  - We report the cloning of a novel PDGFRB fusion gene partner in a patient with a
      chronic myeloproliferative disorder characterized by t(5;14)(q33;q32), who
      responded to treatment with imatinib mesylate. Fluorescence in situ hybridization
      demonstrated that PDGFRB was involved in the translocation. Long distance
      inversion PCR identified KIAA1509 as the PDGFRB fusion partner. KIAA1509 is an
      uncharacterized gene with a predicted coiled-coil oligomerization domain with
      homology to the HOOK family of proteins. The predicted KIAA1509-PDGFRbeta fusion
      protein contains the KIAA1509 coiled-coil domain fused to the cytoplasmic domain
      of PDGFRbeta that includes the tyrosine kinase domain. Imatinib therapy resulted
      in rapid normalization of the patient's blood counts, and subsequent bone marrow
      biopsies and karyotypic analysis were consistent with sustained complete
      remission.

PMID- 15496976
TI  - Multipotent neural precursors express neural and hematopoietic factors, and
      enhance ex vivo expansion of cord blood CD34+ cells, colony forming units and
      NOD/SCID-repopulating cells in contact and noncontact cultures.
AB  - In view of the possible crosstalks between hematopoiesis and neuropoiesis, we
      evaluated two microenvironments, murine neonatal neural cell line C17.2 and
      primary embryonic aorta-gonad-mesonephros (AGM) stromal cells, on the ex vivo
      expansion of CD34+ cells from human cord blood. In a contact culture system,
      C17.2 or AGM cells significantly enhanced the expansion of CD34+ cells to a panel
      of early and committed hematopoietic progenitor cells. In a noncontact transwell
      system, pre-established C17.2 cells significantly increased the expansion of
      total nucleated cells, CD34+ cells and multilineage colony forming cells
      (P<0.01). Expanded cells were infused into nonobese diabetic/severe-combined
      immunodeficient mice. The engraftment of human (hu)CD45+ cells in the bone marrow
      of these mice was consistently higher in all the 10 experiments conducted with
      the support of C17.2 cells when compared with those in respective control groups
      (11.9 vs 2.43%, P=0.03). Using RT-PCR and Southern blot analysis, we showed that
      AGM and C17.2 cells expressed a panel of hematopoietic, bone morphogenetic and
      neurotrophic factors. Our data provided the first evidence on the promoting
      effects of a neural progenitor cell line on hematopoiesis at a noncontact
      condition. The mechanism could be mediated by the expression of multilineage
      regulatory factors.

PMID- 15496977
TI  - Efficacy of melphalan, arsenic trioxide, and ascorbic acid combination therapy
      (MAC) in relapsed and refractory multiple myeloma.

PMID- 15496978
TI  - The novel histone deacetylase inhibitor NVP-LAQ824: an addition to the
      therapeutic armamentarium in leukemia?

PMID- 15496979
TI  - Histone deacetylase inhibitor NVP-LAQ824 has significant activity against myeloid
      leukemia cells in vitro and in vivo.
AB  - NVP-LAQ824 is a novel potent hydroxamic acid-derived histone deacetylase
      inhibitor that induces apoptosis in nanomolar concentrations in myeloid leukemia
      cell lines and patient samples. Here we show the activity of NVP-LAQ824 in acute
      myeloid leukemia cells and BCR/ABL-expressing cells of mouse and human origin,
      both sensitive and resistant to imatinib mesylate (Gleevec, STI-571). Whereas
      imatinib inhibited overall cellular tyrosine phosphorylation in Ba/F3.p210 cells,
      NVP-LAQ824 did not inhibit tyrosine phosphorylation, and did not affect BCR/ABL
      or ABL protein expression. Neither compound was able to inhibit cellular tyrosine
      phosphorylation in the imatinib-resistant Ba/F3.p210-T315I cell line. These data
      taken together suggest that BCR/ABL kinase activity is not a direct target of NVP
      LAQ824. Synergy between NVP-LAQ824 and imatinib was demonstrated against BCR/ABL
      expressing K562 myeloid leukemia cell lines. In addition, we show that NVP-LAQ824
      was well tolerated in vivo in a pre-clinical murine leukemia model, with
      antileukemia activity resulting in significant prolongation of the survival of
      mice when treated with NVP-LAQ824 compared to control mice. Taken together, these
      findings provide the framework for NVP-LAQ824 as a novel therapeutic in myeloid
      malignancies.

PMID- 15496980
TI  - Rapid amplification of immunoglobulin heavy chain switch (IGHS) translocation
      breakpoints using long-distance inverse PCR.
AB  - Molecular cloning of immunoglobulin heavy chain (IGH) translocation breakpoints
      identifies genes of biological importance in the development of normal and
      malignant B cells. Long-distance inverse PCR (LDI-PCR) was first applied to
      amplification of IGH gene translocations targeted to the joining (IGHJ) regions.
      We report here successful amplification of the breakpoint of IGH translocations
      targeted to switch (IGHS) regions by LDI-PCR. To detect IGHS translocations,
      Southern blot assays using 5' and 3' switch probes were performed. Illegitimate
      Smu rearrangements were amplified from the 5' end (5'Smu LDI-PCR) from the
      alternative derivative chromosome, and those of Sgamma or Salpha were amplified
      from the 3' end (3'Sgamma or 3'alpha LDI-PCR) from the derivative chromosome 14.
      Using a combination of these methods, we have succeeded in amplifying IGHS
      translocation breakpoints involving FGFR3/MMSET on 4p16, BCL6 on 3q27, MYC on
      8q24, IRTA1 on 1q21 and PAX5 on 9p13 as well as BCL11A on 2p13 and CCND3 on 6p21.
      The combination of LDI-PCR for IGHJ and IGHS allows rapid molecular cloning of
      almost all IGH gene translocation breakpoints.

PMID- 15496981
TI  - The International Prognostic Scoring System (IPSS) for childhood myelodysplastic
      syndrome (MDS) and juvenile myelomonocytic leukemia (JMML).
AB  - The International Prognostic Scoring System (IPSS) for myelodysplastic syndrome
      (MDS) is based upon weighted data on bone marrow (BM) blast percentage,
      cytopenia, and cytogenetics, separating patients into four prognostic groups. We
      analyzed the value of the IPSS in 142 children with de novo MDS and 166 children
      with juvenile myelomonocytic leukemia (JMML) enrolled in retro- and prospective
      studies of the European Working Group on childhood MDS (EWOG-MDS). Survivals in
      MDS and JMML were analyzed separately. Among the criteria considered by the IPSS
      score, only BM blasts <5% and platelets >100 x 10(9)/l were significantly
      associated with a superior survival in MDS. In JMML, better survival was
      associated with platelets >40 x 10(9)/l, but not with any other IPSS factors
      including cytogenetics. In conclusion, the IPSS is of limited value in both
      pediatric MDS and JMML. The results reflect the differences between
      myelodysplastic and myeloproliferative diseases in children and adults.

PMID- 15496982
TI  - RseP (YaeL), an Escherichia coli RIP protease, cleaves transmembrane sequences.
AB  - Escherichia coli RseP (formerly YaeL) is believed to function as a 'regulated
      intramembrane proteolysis' (RIP) protease that introduces the second cleavage
      into anti-sigma(E) protein RseA at a position within or close to the
      transmembrane segment. However, neither its enzymatic activity nor the substrate
      cleavage position has been established. Here, we show that RseP-dependent
      cleavage indeed occurs within predicted transmembrane sequences of membrane
      proteins in vivo. Moreover, RseP catalyzed the same specificity proteolysis in an
      in vitro reaction system using purified components. Our in vivo and in vitro
      results show that RseP can cleave transmembrane sequences of some model membrane
      proteins that are unrelated to RseA, provided that the transmembrane region
      contains residues of low helical propensity. These results show that RseP has
      potential ability to cut a broad range of membrane protein sequences.
      Intriguingly, it is nevertheless recruited to the sigma(E) stress-response
      cascade as a specific player of RIP.

PMID- 15496983
TI  - Mash1 specifies neurons and oligodendrocytes in the postnatal brain.
AB  - Progenitors in the telencephalic subventricular zone (SVZ) remain mitotically
      active throughout life, and produce different cell types at embryonic, postnatal
      and adult stages. Here we show that Mash1, an important proneural gene in the
      embryonic telencephalon, is broadly expressed in the postnatal SVZ, in
      progenitors for both neuronal and oligodendrocyte lineages. Moreover, Mash1 is
      required at birth for the generation of a large fraction of neuronal and
      oligodendrocyte precursors from the olfactory bulb. Clonal analysis in culture
      and transplantation experiments in postnatal brain demonstrate that this
      phenotype reflects a cell-autonomous function of Mash1 in specification of these
      two lineages. The conservation of Mash1 function in the postnatal SVZ suggests
      that the same transcription mechanisms operate throughout life to specify cell
      fates in this structure, and that the profound changes in the cell types produced
      reflect changes in the signalling environment of the SVZ.

PMID- 15496984
TI  - Binding site for Robo receptors revealed by dissection of the leucine-rich repeat
      region of Slit.
AB  - Recognition of the large secreted protein Slit by receptors of the Robo family
      provides fundamental signals in axon guidance and other developmental processes.
      In Drosophila, Slit-Robo signalling regulates midline crossing and the lateral
      position of longitudinal axon tracts. We report the functional dissection of
      Drosophila Slit, using structure analysis, site-directed mutagenesis and in vitro
      assays. The N-terminal region of Slit consists of a tandem array of four
      independently folded leucine-rich repeat (LRR) domains, connected by disulphide
      tethered linkers. All three Drosophila Robos were found to compete for a single
      highly conserved site on the concave face of the second LRR domain of Slit. We
      also found that this domain is sufficient for biological activity in a chemotaxis
      assay. Other Slit activities may require Slit dimerisation mediated by the fourth
      LRR domain. Our results show that a small portion of Slit is able to induce Robo
      signalling and indicate that the distinct functions of Drosophila Robos are
      encoded in their divergent cytosolic domains.

PMID- 15496985
TI  - Evolving nature of the AP2 alpha-appendage hub during clathrin-coated vesicle
      endocytosis.
AB  - Clathrin-mediated endocytosis involves the assembly of a network of proteins that
      select cargo, modify membrane shape and drive invagination, vesicle scission and
      uncoating. This network is initially assembled around adaptor protein (AP)
      appendage domains, which are protein interaction hubs. Using crystallography, we
      show that FxDxF and WVxF peptide motifs from synaptojanin bind to distinct
      subdomains on alpha-appendages, called 'top' and 'side' sites. Appendages use
      both these sites to interact with their binding partners in vitro and in vivo.
      Occupation of both sites simultaneously results in high-affinity reversible
      interactions with lone appendages (e.g. eps15 and epsin1). Proteins with multiple
      copies of only one type of motif bind multiple appendages and so will aid adaptor
      clustering. These clustered alpha(appendage)-hubs have altered properties where
      they can sample many different binding partners, which in turn can interact with
      each other and indirectly with clathrin. In the final coated vesicle, most
      appendage binding partners are absent and thus the functional status of the
      appendage domain as an interaction hub is temporal and transitory giving
      directionality to vesicle assembly.

PMID- 15496986
TI  - High-efficiency bypass of DNA damage by human DNA polymerase Q.
AB  - Endogenous DNA damage arises frequently, particularly apurinic (AP) sites. These
      must be dealt with by cells in order to avoid genotoxic effects. DNA polymerase
      theta; is a newly identified enzyme encoded by the human POLQ gene. We find that
      POLQ has an exceptional ability to bypass an AP site, inserting A with 22% of the
      efficiency of a normal template, and continuing extension as avidly as with a
      normally paired base. POLQ preferentially incorporates A opposite an AP site and
      strongly disfavors C. On nondamaged templates, POLQ makes frequent errors,
      incorporating G or T opposite T about 1% of the time. This very low fidelity
      distinguishes POLQ from other A-family polymerases. POLQ has three sequence
      insertions between conserved motifs in its catalytic site. One insert of
      approximately 22 residues into the tip of the polymerase thumb subdomain is
      predicted to confer considerable flexibility and additional DNA contacts to
      affect enzyme fidelity. POLQ is the only known enzyme that efficiently carries
      out both the insertion and extension steps for bypass of AP sites, commonly
      formed as endogenous genomic lesions.

PMID- 15496988
TI  - Editorial.

PMID- 15496987
TI  - An alternative strategy for bacterial ribosome synthesis: Bacillus subtilis rRNA
      transcription regulation.
AB  - As an approach to the study of rRNA synthesis in Gram-positive bacteria, we
      characterized the regulation of the Bacillus subtilis rrnB and rrnO rRNA
      promoters. We conclude that B. subtilis and Escherichia coli use different
      strategies to control rRNA synthesis. In contrast to E. coli, it appears that the
      initiating NTP for transcription from B. subtilis rRNA promoters is GTP, promoter
      strength is determined primarily by the core promoter (-10/-35 region), and
      changes in promoter activity always correlate with changes in the intracellular
      GTP concentration. rRNA promoters in B. subtilis appear to be regulated by
      changes in the initiating NTP pools, but in some growth transitions, changes in
      rRNA promoter activity are also dependent on relA, which codes for ppGpp
      synthetase. In contrast to the situation for E. coli where ppGpp decreases rRNA
      promoter activity by directly inhibiting RNA polymerase, it appears that ppGpp
      may not inhibit B. subtilis RNA polymerase directly. Rather, increases in the
      ppGpp concentration might reduce the available GTP pools, thereby modulating rRNA
      promoter activity indirectly.

PMID- 15496989
TI  - Computed Tomography is Diagnostic in the Cervical Imaging of Helmeted Football
      Players With Shoulder Pads.
AB  - OBJECTIVE: Prospective, observational case series evaluating the value of
      cervical spine computed tomography (CT) scans in the initial evaluation of a
      helmeted football player with suspected cervical spine injury. SUBJECTS: Five
      asymptomatic male football players, fully equipped and immobilized on a
      backboard. DESIGN: Multiple 3.0-mm, helically acquired, axially displayed CT
      images of the cervical spine were obtained from the skull base inferiorly through
      T1, with images filmed at soft tissue and bone windows. Sagittal and coronal
      reformatted images were performed. Software was used to minimize metallic
      artifact. MEASUREMENTS: All series were reviewed by a Board-certified
      neuroradiologist for image clarity and diagnostic capability. RESULTS: Lateral
      scout films demonstrated mild segmental degradation, depending on the location of
      the metallic snaps overlying the spine. Anteroposterior scout films and bone
      window images were of diagnostic quality. The soft tissue windows showed minimal
      localized artifact occurring at the same levels as in the lateral scout views.
      This minimal beam-hardening streak artifact did not affect the diagnostic quality
      of the soft tissue windows. Reconstructed images were uniformly of clinical
      diagnostic quality. DISCUSSION: When CT scans were reviewed as a unit, sufficient
      information was available to allow reliable clinical decisions about the helmeted
      football player. In light of recent publications demonstrating the difficulty of
      obtaining adequate radiographs to evaluate cervical spine injury in equipped
      football players, helmeted athletes may undergo CT scanning without any
      significant diagnostic limitations.

PMID- 15496990
TI  - Low-Level Laser Therapy Facilitates Superficial Wound Healing in Humans: A Triple
      Blind, Sham-Controlled Study.
AB  - OBJECTIVE: Low-level laser therapy (LLLT) has been promoted for its beneficial
      effects on tissue healing and pain relief. However, according to the results of
      in vivo studies, the effectiveness of this modality varies. Our purpose was to
      assess the putative effects of LLLT on healing using an experimental wound model.
      DESIGN AND SETTING: We used a randomized, triple-blind, placebo-controlled design
      with 2 within-subjects factors (wound and time) and 1 between-subjects factor
      (group). Data were collected in the laboratory setting. SUBJECTS: Twenty-two
      healthy subjects (age = 21 +/- 1 years, height = 175.6 +/- 9.8 cm, mass = 76.2 +/
      14.2 kg). MEASUREMENTS: Two standardized 1.27-cm(2) abrasions were induced on
      the anterior forearm. After wound cleaning, standardized digital photos were
      recorded. Each subject then received LLLT (8 J/cm(2); treatment time = 2 minutes,
      5 seconds; pulse rate = 700 Hz) to 1 of the 2 randomly chosen wounds from either
      a laser or a sham 46-diode cluster head. Subjects reported back to the laboratory
      on days 2 to 10 to be photographed and receive LLLT and on day 20 to be
      photographed. Data were analyzed for wound contraction (area), color changes
      (chromatic red), and luminance. RESULTS: A group x wound x time interaction was
      detected for area measurements. At days 6, 8, and 10, follow-up testing revealed
      that the laser group had smaller wounds than the sham group for both the treated
      and the untreated wounds (P < .05). No group x wound x time differences were
      detected for chromatic red or luminance. CONCLUSIONS: The LLLT resulted in
      enhanced healing as measured by wound contraction. The untreated wounds in
      subjects treated with LLLT contracted more than the wounds in the sham group, so
      LLLT may produce an indirect healing effect on surrounding tissues. These data
      indicate that LLLT is an effective modality to facilitate wound contraction of
      partial-thickness wounds.

PMID- 15496991
TI  - Three-MHz Ultrasound Heats Deeper Into the Tissues Than Originally Theorized.
AB  - OBJECTIVE: To measure muscle temperature of ultrasound at 1-MHz and 3-MHz
      frequencies at a depth of 2.5 cm and to compare treatment durations for vigorous
      heating (increase of 4 degrees C) and for heating to 40 degrees C. DESIGN AND
      SETTING: A counterbalanced, repeated-measures design with 1 fixed, independent
      variable, 1.5-W/cm(2) ultrasound treatment (1 MHz, 3 MHz, or control [sham])
      using a Theratouch 7.7 ultrasound device. Dependent variables were end-treatment
      temperature at 2.5 cm, time to vigorous heating, and time to reach 40 degrees C.
      SUBJECTS: Eighteen healthy volunteers (age = 24.6 +/- 2.3 years, height = 173.0
      +/- 9.7 cm, mass = 72.0 +/- 16.3 kg) without a history of lower leg injury.
      MEASUREMENTS: The medial triceps surae intramuscular temperature at 2.5 cm was
      measured every 10 seconds using an implantable thermocouple. Each of the 3
      ultrasound frequencies was applied in counterbalanced order at 24-hour intervals.
      RESULTS: Ultrasound of 3 MHz produced both vigorous heating (at 3.4 minutes) and
      an absolute temperature of 40 degrees C (at 4 minutes). CONCLUSIONS: Our results
      suggest that 3-MHz ultrasound heats 0.5 cm deeper than suggested by others. With
      our machine, 3-MHz ultrasound was more effective in heating muscle at this depth
      than 1-MHz ultrasound.

PMID- 15496992
TI  - Thermal Responses in Football and Cross-Country Athletes During Their Respective
      Practices in a Hot Environment.
AB  - OBJECTIVE: To determine if football (FB) players and cross-country (CC) runners
      had different thermal responses to their respective training sessions. DESIGN AND
      SETTING: On days 4 and 8 of preseason training, we assessed core (T(c)) and skin
      (T(sk)) temperatures. SUBJECTS: Fifteen collegiate athletes volunteered: 10 FB
      players (age = 21.2 +/- 1.14 years, height = 193.5 +/- 4.8 cm, mass = 116.6 +/-
      16.3 kg, and V(2max) = 44.7 +/- 9.4 mLkg(-1)min(-1)) and 5 CC runners (age = 22.8
      +/- 2.77 years, height = 176.3 +/- 8.9 cm, mass = 71.16 +/- 8.9 kg, and V(2max) =
      71.3 +/- 6.18 mLkg(-1)min(-1)). MEASUREMENTS: We measured T(c) using ingestible
      sensors before, during, and immediately after exercise. The T(sk) was measured at
      the calf, forearm, back, chest, and forehead sites. Level of dehydration was
      assessed by urine specific gravity. RESULTS: Mean wet-bulb temperature was 74
      degrees F (23.33 degrees C). Resting T(c) in shorts and T-shirts was higher in
      the FB group. The T(c) midway through practices and runs was higher in the CC and
      FB subjects when active, compared with the FB subjects when inactive.
      Postexercise T(c) was higher in the CC group than the FB group with pads, and
      postconditioning T(c) was higher in the FB subjects with pads versus no pads.
      Forehead, chest, back, and mean weighted T(sk) were higher in the FB group. The
      T(c) and urine specific gravity were not correlated. CONCLUSIONS: The T(c)
      fluctuated in the FB subjects during practice depending on exercise intensity,
      whereas T(c) increased steadily in the CC subjects during continuous running.
      Thus, CC athletes may have to decrease intensity to maintain thermoregulation.
      Our FB players seemed to dissipate heat adequately during rest periods.

PMID- 15496993
TI  - Balance Recovers Within 20 Minutes After Exertion as Measured by the Balance
      Error Scoring System.
AB  - OBJECTIVE: To determine a balance recovery timeline after a functional exertion
      protocol using the Balance Error Scoring System (BESS). DESIGN AND SETTING: Five
      subject groups (4 test, 1 control) were tested 3 times during 1 session: once
      before the exertion protocol (pretest) and twice after the exertion protocol
      (posttest I and posttest II). Posttest I occurred at staggered intervals of 0, 5,
      10, and 15 minutes, depending on experimental group assignment, and posttest II
      occurred at 20 minutes. SUBJECTS: One hundred subjects (80 test, 20 control)
      volunteered to participate in this study. None of the subjects had a balance
      disorder, mild head injury, or lower extremity injury in the 6 months before
      testing. MEASUREMENTS: We assessed balance using the BESS, assigning a score for
      each stance-surface condition. RESULTS: We found a significant decrease in BESS
      performance after the exertion protocol in all test groups, with exertion having
      the greatest effect on the tandem and single-leg stance conditions. All subjects
      recovered by posttest II, which was administered 20 minutes after cessation of
      the exertion protocol. CONCLUSIONS: Athletic trainers need to be aware of the
      effect of exertion when administering the BESS after physical activity. Athletic
      trainers can expect the BESS performance of healthy athletes to return to
      baseline levels within 20 minutes of rest.

PMID- 15496994
TI  - Dynamic Stabilization Time After Isokinetic and Functional Fatigue.
AB  - OBJECTIVE: To compare the effects of an isokinetic fatigue protocol and a
      functional fatigue protocol on time to stabilization (TTS), ground reaction force
      (GRF), and joint kinematics during a jump landing. DESIGN AND SETTING: Subjects
      were assessed on 2 occasions for TTS, GRF, and joint kinematics immediately
      before and after completing a fatigue protocol. One week separated the 2
      sessions, and the order of fatigue protocols was randomly assigned and
      counterbalanced. SUBJECTS: Twenty healthy male (n = 8, age = 21.8 +/- 1.4 years,
      height = 180.6 +/- 7.6 cm, and mass = 74.1 +/- 13.0 kg) and female (n = 12, age =
      22.2 +/- 2.1 years, height = 169.3 +/- 9.8 cm, and mass = 62.5 +/- 10.1 kg)
      subjects volunteered to participate. MEASUREMENTS: Subjects performed 2-legged
      jumps equivalent to 50% of maximum jump height, followed by a single-leg landing
      onto the center of a forceplate 70 cm from the starting position. Peak vertical
      GRF and vertical, medial-lateral, and anterior-posterior TTS were obtained from
      forceplate recordings. Maximum ankle dorsiflexion, knee-flexion, and knee-valgum
      angles were determined using 3-dimensional motion analysis. RESULTS: A 2-way
      analysis of variance with repeated measures revealed no significant differences
      when comparing TTS, GRF, and joint kinematics after isokinetic and functional
      fatigue protocols. CONCLUSIONS: No difference was noted between isokinetic and
      functional fatigue protocols relative to dynamic stability when landing from a
      jump.

PMID- 15496995
TI  - Eccentric Training and Static Stretching Improve Hamstring Flexibility of High
      School Males.
AB  - OBJECTIVE: To determine if the flexibility of high-school-aged males would
      improve after a 6-week eccentric exercise program. In addition, the changes in
      hamstring flexibility that occurred after the eccentric program were compared
      with a 6-week program of static stretching and with a control group (no
      stretching). DESIGN AND SETTING: We used a test-retest control group design in a
      laboratory setting. Subjects were assigned randomly to 1 of 3 groups: eccentric
      training, static stretching, or control. SUBJECTS: A total of 69 subjects, with a
      mean age of 16.45 +/- 0.96 years and with limited hamstring flexibility (defined
      as 20 degrees loss of knee extension measured with the thigh held at 90 degrees
      of hip flexion) were recruited for this study. MEASUREMENTS: Hamstring
      flexibility was measured using the passive 90/90 test before and after the 6-week
      program. RESULTS: Differences were significant for test and for the test-by-group
      interaction. Follow-up analysis indicated significant differences between the
      control group (gain = 1.67 degrees ) and both the eccentric-training (gain =
      12.79 degrees ) and static-stretching (gain = 12.05 degrees ) groups. No
      difference was found between the eccentric and static-stretching groups.
      CONCLUSIONS: The gains achieved in range of motion of knee extension (indicating
      improvement in hamstring flexibility) with eccentric training were equal to those
      made by statically stretching the hamstring muscles.

PMID- 15496996
TI  - A Skinfold Model to Predict Fat-Free Mass in Female Athletes.
AB  - OBJECTIVE: Despite widespread use of skinfolds to estimate body fatness, few
      prediction models have been validated on female athletes. Most skinfold models
      have been validated with hydrodensitometry, which does not account for the
      variability in bone density that may exist among female athletes. Our purpose was
      to develop a skinfold model that predicts fat-free mass (FFM) in female
      collegiate athletes. DESIGN AND SETTING: A skinfold model was developed using
      dual-energy x-ray absorptiometry (DEXA) as the criterion method. Four skinfold
      measures (abdominal, suprailiac, thigh, triceps), height, and weight were entered
      into a regression model. The best model was developed and validated by
      calculating the predicted error sum of squares statistic. SUBJECTS: Study
      participants included 101 National Collegiate Athletic Association Division I
      female athletes (age = 20.3 +/- 1.4 years, height = 166.7 +/- 7.8 cm, mass = 63.1
      +/- 8.1 kg) from several sports. MEASUREMENTS: Each participant's FFM was
      measured via DEXA. Skinfold thicknesses were measured and entered into the
      regression model. RESULTS: The final regression model included mass and abdominal
      and thigh skinfolds: FFM = 8.51 + (0.809 x mass) - (0.178 x abdominal skinfold) -
      (0.225 x thigh skinfold). The model showed excellent predictive ability (R =
      0.98, standard error of the estimate = 1.1 kg). Pairwise comparisons indicated
      that prediction error showed no overprediction or underprediction bias.
      CONCLUSIONS: In female collegiate athletes, FFM can be predicted accurately from
      body mass and abdominal and thigh skinfolds. This model is practical and can be
      used in most athletic settings.

PMID- 15496997
TI  - A Prospective Study of Overuse Knee Injuries Among Female Athletes With Muscle
      Imbalances and Structural Abnormalities.
AB  - OBJECTIVE: To prospectively examine the influence of hamstring-to-quadriceps
      (H:Q) ratio and structural abnormalities on the prevalence of overuse knee
      injuries among female collegiate athletes. DESIGN AND SETTING: We used chi-square
      2 x 2 contingency tables and the Fischer exact test to examine associations among
      H:Q ratios, structural abnormalities, and overuse knee injuries. SUBJECTS: Fifty
      three apparently healthy women (age = 19.4 +/- 1.3 years, height = 167.6 +/- 10.1
      cm, mass = 65.0 +/- 10.0 kg) from National Collegiate Athletic Association
      Division I women's field hockey (n = 23), soccer (n = 20), and basketball teams
      (n = 10) volunteered. MEASUREMENTS: The H:Q ratio was determined from a preseason
      isokinetic test on a Biodex system at 60 degrees /s and 300 degrees /s. We
      measured athletes for genu recurvatum and Q-angles with a 14-in (35.56-cm)
      goniometer. Iliotibial band flexibility was assessed via the Ober test. RESULTS:
      Ten overuse knee injuries (iliotibial band friction syndromes = 5, patellar
      tendinitis = 3, patellofemoral syndrome = 1, pes anserine tendinitis = 1)
      occurred in 9 athletes. The H:Q ratio below the normal range at 300 degrees /s (P
      = 0.047) was associated with overuse knee injuries, as was the presence of genu
      recurvatum (P = 0.004). In addition, athletes possessing lower H:Q ratios at 300
      degrees /s and genu recurvatum incurred more overuse knee injuries than athletes
      without these abnormalities (P = 0.001). CONCLUSIONS: The presence of genu
      recurvatum and an H: Q ratio below normal range was associated with an increased
      prevalence of overuse knee injuries among female collegiate athletes. Further
      investigation is needed to clarify which preseason screening procedures may
      identify collegiate athletes who are susceptible to overuse knee injuries.

PMID- 15496998
TI  - Does Cryotherapy Improve Outcomes With Soft Tissue Injury?
AB  - REFERENCE: Bleakley C, McDonough S, MacAuley D. The use of ice in the treatment
      of acute soft-tissue injury: a systematic review of randomized controlled trials.
      Am J Sport Med. 2004; 32:251-261. CLINICAL QUESTION: What is the clinical
      evidence base for cryotherapy use? DATA SOURCES: Studies were identified by using
      a computer-based literature search on a total of 8 databases: MEDLINE, Proquest,
      ISI Web of Science, Cumulative Index to Nursing and Allied Health (CINAHL) on
      Ovid, Allied and Complementary Medicine Database (AMED) on Ovid, Cochrane
      Database of Systematic Reviews, Cochrane Database of Abstracts of Reviews of
      Effectiveness, and Cochrane Controlled Trials Register (Central). This was
      supplemented with citation tracking of relevant primary and review articles.
      Search terms included surgery,orthopaedics,sports injury,soft tissue
      injury,sprains and strains,contusions,athletic injury,acute,compression,
      cryotherapy,ice,RICE, andcold. STUDY SELECTION: To be included in the review,
      each study had to fulfill the following conditions: be a randomized, controlled
      trial of human subjects; be published in English as a full paper; include
      patients recovering from acute soft tissue or orthopaedic surgical interventions
      who received cryotherapy in inpatient, outpatient, or home-based treatment, in
      isolation or in combination with placebo or other therapies; provide comparisons
      with no treatment, placebo, a different mode or protocol of cryotherapy, or other
      physiotherapeutic interventions; and have outcome measures that included function
      (subjective or objective), pain, swelling, or range of motion. DATA EXTRACTION:
      The study population, interventions, outcomes, follow-up, and reported results of
      the assessed trials were extracted and tabulated. The primary outcome measures
      were pain, swelling, and range of motion. Only 2 groups reported adequate data
      for return to normal function. All eligible articles were rated for methodologic
      quality using the PEDro scale. The PEDro scale is a checklist that examines the
      believability (internal validity) and the interpretability of trial quality. The
      11-item checklist yields a maximum score of 10 if all criteria are satisfied. The
      intraclass correlation coefficient and kappa values are similar to those reported
      for 3 other frequently used quality scales (Chalmers Scale, Jadad Scale, and
      Maastricht List). Two reviewers graded the articles, a method that has been
      reported to be more reliable than one evaluator. MAIN RESULTS: Specific search
      criteria identified 55 articles for review, of which 22 were eligible randomized,
      controlled clinical trials. The articles' scores on the PEDro scale were low,
      ranging from 1 to 5, with an average score of 3.4. Five studies provided adequate
      information on the subjects' baseline data, and only 3 studies concealed
      allocation during subject recruitment. No studies blinded their therapist's
      administration of therapy, and just 1 study blinded subjects. Only 1 study
      included an intention-to-treat analysis. The average number of subjects in the
      studies was 66.7; however, only 1 group undertook a power analysis. The types of
      injuries varied widely (eg, acute or surgical). No authors investigated subjects
      with muscle contusions or strains, and only 5 groups studied subjects with acute
      ligament sprains. The remaining 17 groups examined patients recovering from
      operative procedures (anterior cruciate ligament repair, knee arthroscopy,
      lateral retinacular release, total knee and hip arthroplasties, and carpal tunnel
      release). Additionally, the mode of cryotherapy varied widely, as did the
      duration and frequency of cryotherapy application. The time period when
      cryotherapy was applied after injury ranged from immediately after injury to 1 to
      3 days postinjury. Adequate information on the actual surface temperature of the
      cooling device was not provided in the selected studies. Most authors recorded
      outcome variables over short periods (1 week), with the longest reporting follow
      ups of pain, swelling, and range of motion recorded at 4 weeks postinjury. Data
      in that study were insufficient to calculate effect size. Nine studies did not
      provide data of the key outcome measures, so individual study effect estimates
      could not be calculated. A total of 12 treatment comparisons were made. Ice
      submersion with simultaneous exercises was significantly more effective than heat
      and contrast therapy plus simultaneous exercises at reducing swelling. Ice was
      reported to be no different from ice and low-frequency or high-frequency electric
      stimulation in effect on swelling, pain, and range of motion. Ice alone seemed to
      be more effective than applying no form of cryotherapy after minor knee surgery
      in terms of pain, but no differences were reported for range of motion and girth.
      Continuous cryotherapy was associated with a significantly greater decrease in
      pain and wrist circumference after surgery than intermittent cryotherapy.
      Evidence was marginal that a single simultaneous treatment with ice and
      compression is no more effective than no cryotherapy after an ankle sprain. The
      authors reported ice to be no more effective than rehabilitation only with regard
      to pain, swelling, and range of motion. Ice and compression seemed to be
      significantly more effective than ice alone in terms of decreasing pain.
      Additionally, ice, compression, and a placebo injection reduced pain more than a
      placebo injection alone. Lastly, in 8 studies, there seemed to be little
      difference in the effectiveness of ice and compression compared with compression
      alone. Only 2 of the 8 groups reported significant differences in favor of ice
      and compression. CONCLUSIONS: Based on the available evidence, cryotherapy seems
      to be effective in decreasing pain. In comparison with other rehabilitation
      techniques, the efficacy of cryotherapy has been questioned. The exact effect of
      cryotherapy on more frequently treated acute injuries (eg, muscle strains and
      contusions) has not been fully elucidated. Additionally, the low methodologic
      quality of the available evidence is of concern. Many more high-quality studies
      are required to create evidence-based guidelines on the use of cryotherapy. These
      must focus on developing modes, durations, and frequencies of ice application
      that will optimize outcomes after injury.

PMID- 15496999
TI  - Simmering innards: Does irritable bowel syndrome have an immunological basis?

PMID- 15497000
TI  - A Canadian clinical practice algorithm for the management of patients with
      nonvariceal upper gastrointestinal bleeding.
AB  - AIM: To use current evidence-based recommendations to provide a user-friendly
      clinical algorithm for the management of upper gastrointestinal bleeding, adapted
      to the Canadian environment. METHODS: A multidisciplinary consensus group of 25
      participants representing 11 national societies used a seven-step approach to
      develop recommendations according to accepted standards. Sources of data included
      narrative and systematic reviews as well as published and new meta-analyses. A
      small writing subgroup subsequently created the algorithm. RESULTS:
      Recommendations emphasize appropriate initial resuscitation of the patient and a
      multidisciplinary approach to clinical risk stratification that determines the
      need for early endoscopy. Early endoscopy allows safe and prompt discharge of
      selected patients classified as low risk. Endoscopic hemostasis is reserved for
      patients with high-risk endoscopic lesions. Although monotherapy with injection
      or thermal coagulation is effective, the combination is superior to either
      treatment alone. High-dose intravenous proton-pump inhibition is recommended in
      patients who have undergone successful endoscopic therapy. Routine second-look
      endoscopy is not recommended. Patients with upper gastrointestinal bleeding
      secondary to ulcer disease should be tested and treated for Helicobacter pylori
      infection. CONCLUSIONS: This algorithm should facilitate appropriate risk
      stratification, use of endoscopic therapy and the appropriate utilization of
      proton-pump inhibition to optimize the care of patients with upper
      gastrointestinal bleeding. The algorithm should be customized to the resources of
      individual medical centres. Its application should be studied with appropriate
      outcomes recorded and validation performed.

PMID- 15497001
TI  - Survival and prognostic factors in patients with hepatocellular carcinoma treated
      by percutaneous ethanol injection: a 10-year experience.
AB  - The treatment of early and intermediate stage hepatocellular carcinoma (HCC) is
      still debated. Surgical treatments are considered to be the only curative
      procedures available, and only for a minority of patients. Percutaneous ethanol
      injection (PEI) is an established technique for the ablation of HCC nodules, and
      shows survival rates similar to those of resection. The efficacy of PEI in
      patients with biopsy-proven viral cirrhosis and small to intermediate inoperable
      HCC was evaluated. One hundred twenty-seven patients (85 men, 42 women, mean age
      63 years, range 51 to 92 years, 115 hepatitis C virus-positive, 12 hepatitis B
      virus-positive) were enrolled between January 1993 and December 2002. They all
      underwent a standard PEI procedure and were prospectively followed-up. Overall
      median survival rate was 28 months (range six to 112 months). The following
      parameters were associated with a significantly longer survival: nodule diameter
      smaller than 30 mm (P=0.0480), the presence of a perinodular boundary (P=0.0008),
      serum alpha-fetoprotein less than 20 ng/mL (P=0.0104), a Child-Pugh A class score
      (P<0.0001) or a Cancer of the Liver Italian Program score of 0 (P<0.0001) and the
      presence or absence of small esophageal varices (P=0.013). The 19 patients with
      all these favourable characteristics showed an overall median survival of 61
      months. An alpha-fetoprotein below 20 ng/mL was associated with significantly
      longer disease-free survival (P=0.0009). The Child-Pugh and Cancer of the Liver
      Italian Program scores were effective in predicting prognosis of these patients.
      In conclusion, PEI still represents a safe and economically sound treatment for
      HCC.

PMID- 15497002
TI  - Patterns of use of endoscopic retrograde cholangiopancreatography in a Canadian
      province.
AB  - BACKGROUND: Data on current endoscopic retrograde cholangiopancreatography (ERCP)
      practice patterns drawn from large population-based samples are limited. METHODS:
      Patterns of ERCP use were determined using billing records for ERCP,
      sphincterotomy, stone extraction or stent placement performed between April 1,
      1994 and March 31, 2002 in Alberta from a population-based administrative
      database. Age-sex adjusted rates (per 1000 population) were calculated using the
      1991 Canadian population as the standard. RESULTS: The eight-year average ERCP
      rate was 0.98 without evidence of an increasing or decreasing trend over time.
      The ERCP rate was 0.85 in men and 1.12 in women. Significant regional variation
      in ERCP rates was seen, ranging from a low of 0.64 to a high of 1.27. The
      proportion of procedures that were therapeutic increased from 33% in 1994 to 70%
      in 2001. The likelihood of a procedure being considered therapeutic varied with
      the age and sex of the patient as well as the health region in which the
      procedure was performed. CONCLUSIONS: The ERCP rate remained relatively stable
      over an eight-year time period, but the proportion of procedures that were
      therapeutic increased dramatically. Important regional variation in ERCP rates
      and therapeutic procedures exists.

PMID- 15497003
TI  - Benzocaine-induced methemoglobinemia: a condition of which all endoscopists
      should be aware.
AB  - Methemoglobinemia is a rare complication that can occur with the use of
      benzocaine-containing compounds. Two cases of methemoglobinemia are reported, and
      the pathophysiology and treatment of methemoglobinemia are reviewed. Both
      patients received topical 20% benzocaine spray before endoscopy. Immediately
      following the procedure, there was a reduction in O2 saturation assessed by pulse
      oximetry that was refractory to O2 therapy. Dramatic peripheral and central
      cyanosis developed. O2 saturation measured by pulse oximetry ranged from 83% to
      87% on O2 by nasal prongs and 100% O2 by a nonrebreathing mask. Both patients
      were mildly confused and one patient complained of a significant headache. The
      diagnosis of methemoglobinemia was considered and arterial blood gas sampling was
      performed. In both patients, the arterial blood had a chocolate brown colour. A
      methemoglobin level of 48% and 18% was noted in patient 1 and patient 2,
      respectively. Both patients were treated with methylene blue, resulting in a
      significant improvement with gradual normalization of their O2 saturation within
      10 min to 30 min. The use of benzocaine spray may not markedly alter the
      patient's perception of endoscopy and thus, the routine use of these agents
      should be questioned. If such agents are used, the physician must be aware of
      this association to prevent a delay in the diagnosis and management of this rare,
      but potentially lethal, condition.

PMID- 15497005
TI  - Quantitation of severe acute respiratory syndrome coronavirus genome by real-time
      polymerase chain reaction assay using minor groove binder DNA probe technology.
AB  - The ability to rapidly recognize severe acute respiratory syndrome coronavirus
      (SARS-CoV) as a cause of infections is critical to quickly limiting further
      spread of the disease. A rapid, sensitive, and specific laboratory diagnostic
      test is needed to confirm outbreaks of SARS-CoV infection and distinguish it from
      other diseases that can cause similar clinical symptoms. An improved TaqMan
      technology using minor groove binder (MGB) probes was used to detect and quantify
      SARS-CoV in suspected patients. SARS-CoV primers and probe were designed based on
      the open reading frame 1b sequence, which encodes coronavirus replicase protein.
      A linear standard curve with R2 > 0.99 was obtained, and the threshold
      sensitivity was 10 genome equivalents per reaction. Interassay coefficients of
      variation were 1.73 to 2.72%, indicating good reproducibility of this method. A
      total of 228 specimens from 151 suspected patients were quantified by this
      method, 13 specimens from 6 patients were positive with viral load range from 362
      to 36,240,000 genome equivalents/mL. In conclusion, the high sensitivity and
      reproducibility of the real-time polymerase chain reaction SARS-CoV RNA
      quantitation using MGB probe allowed the screening of large numbers of clinical
      samples.

PMID- 15497006
TI  - Characteristics of a dengue hemorrhagic fever outbreak in 2001 in Kaohsiung.
AB  - A dengue outbreak occurred in Kaohsiung City starting in July in 2001. We studied
      the clinical profile of all patients admitted to Kaohsiung Veterans General
      Hospital during this outbreak from July 2001 to January 2002. A total of 25 cases
      of clinically suspected dengue fever were treated during this period, and 13 of
      them were confirmed by laboratory results (13/25; 52%). Eleven of the 25 patients
      (11/25; 44%) were admitted. The mean age of the patients with laboratory
      confirmation of infection was 53 years (range, 7 to 85 years). Headache (7/13;
      53.8%), bone pain (8/13; 61.5%), myalgia (10/13; 76.9%), abdominal pain (7/13;
      53.8%), and skin rash (9/13; 69.2%) were the most common presentations. A high
      proportion of patients were classified as having dengue hemorrhagic fever (DHF)
      [6/13; 46.2%] and 2 of these patients had dengue shock syndrome (DSS) based on
      the World Health Organization criteria. Pretibial petechia (6/13; 46.1%),
      gastrointestinal bleeding (6/13; 46.1%), and hemoptysis (4/13; 30.8%) were the
      most common hemorrhagic manifestations. The average hospital stay was 7.1 days.
      Thrombocytopenia was very common and 84.6% patients had a platelet count less
      than 100,000/mm3. Monocytosis was found in all patients. Few patients required
      blood or platelet concentrate transfusion. The 2 patients who developed DSS both
      survived. All patients recovered completely without any obvious sequela. In
      conclusion, there was a high percentage of DHF among patients in the dengue
      outbreak in 2001. Increasing rates of DHF compared to previous reports from
      Taiwan may be a sign of hyperendemicity (multiple serotypes present) of the
      dengue virus in Kaohsiung City and its greater likelihood elsewhere in Taiwan.
      Prevention and control of both dengue fever and DHF have thus become increasingly
      important.

PMID- 15497007
TI  - Clinical presentations and virologic characteristics of primary human
      immunodeficiency virus type-1 infection in a university hospital in Taiwan.
AB  - Clinical manifestations of primary human immunodeficiency virus (HIV) infection
      (acute retroviral syndrome) and virologic characteristics of HIV-1 have rarely
      been described in Taiwan. Medical records of patients followed at the National
      Taiwan University Hospital between June 1994 and September 2003 were
      retrospectively reviewed to identify HIV-infected patients who were diagnosed
      with primary HIV infection. Blood specimens obtained at the diagnosis of primary
      HIV infection were submitted for viral subtyping and genotypic resistance assay.
      Twenty out of 940 patients were diagnosed with acute retroviral syndrome during
      the study period. All of the patients were males, with a median age of 31 years
      (range, 23 to 42 years); all were men who had sex with men. The most common
      clinical manifestations were fever (95%), generalized lymphadenopathy (75%),
      pharyngitis (70%), skin rashes (70%), and gastrointestinal symptoms (60%)
      including nausea, vomiting, and diarrhea. Thrombocytopenia (35%), leukopenia
      (35%), and elevated liver function test (50%) were seen in the laboratory tests.
      The median CD4 lymphocyte count was 312 cells/microL (range, 112-520
      cells/microL), and the plasma HIV RNA load by reverse transcriptase-polymerase
      chain reaction was 230,500 copies/mL (range, 602 --> 750,000 copies/mL). No major
      resistance mutations on protease or reverse transcriptase were identified in the
      11 available viral isolates. We conclude that primary HIV infection was rarely
      diagnosed in the designated hospital for HIV care in Taiwan. More education of
      health care providers and counseling of persons at risk to increase awareness of
      HIV infection are urgently needed in Taiwan in order to facilitate earlier
      diagnosis of primary HIV infection and prevent further transmission.

PMID- 15497008
TI  - Molecular diagnosis of Wiskott-Aldrich syndrome in Taiwan.
AB  - The spectrum of Wiskott-Aldrich syndrome (WAS) mutation in Han Chinese residing
      in Taiwan has not been previously reported. We describe a multidisciplinary
      approach to the molecular diagnosis of WAS which could be applied to clinical
      diagnosis, carrier prediction, and prenatal diagnosis. A total of 6 male
      patients, from 6 independent families, were referred for the molecular diagnosis
      of WAS. The respective methylation status of the 6 X chromosomes in peripheral
      blood leukocytes from obligatory female carriers was analyzed initially, followed
      by analysis of the level of expression of WAS protein (WASP) in peripheral
      leukocytes from patients, using a Western blotting technique. The analysis of the
      specific WAS gene mutation was done by direct sequencing. Mutations were
      identified in the WAS gene of all patients. Mutations identified included p.R13X,
      p.R41X, p.S82P, IVS1-1 G --> C, p.L342TFsX493, and a large deletion. Four
      patients had no WASP expression in peripheral leukocytes obtained before bone
      marrow transplantation. Several female carriers in the families of the 6 patients
      with such mutations were confirmed. One prenatal diagnosis was made in a fetus
      and he did not inherit the mutation. The importance of mutations in the first 2
      exons of the WAS gene was demonstrated in this study, which represented 5 of the
      6 mutations identified in 6 patients. The use of a multidisciplinary approach
      including DNA and protein analysis is required for molecular diagnosis and
      genetic counseling of WAS.

PMID- 15497009
TI  - Correlation of viral factors with cervical cancer in Taiwan.
AB  - The correlation of viral factors with cervical cancer was investigated. 27
      cervical cancer biopsies and 29 normal cervical scrapings were determined by
      polymerase chain reaction method for 6 viruses, including human papillomavirus
      (HPV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus
      (HSV)-1, HSV-2, and human herpes virus (HHV)-8. Among 27 biopsies of cervical
      cancer, HPV was identified in 18. Of these HPV-positive specimens, 9 cases of HPV
      type 16 were identified, 2 cases of HPV type 18 and 1 case of mixed infection
      with HPV types 16 and 18 were identified. Among the HPV types detected, type-16
      is the most closely associated with cervical cancer and type-18 ranks second. Of
      the remaining 6 cases, 1 case of HPV-45, 1 case of mixed infection with HPV type
      35, CMV and HSV-2, and 4 cases of unidentified HPV type were also found. EBV, HSV
      1 and HHV-8 were not found in the cervical cancer samples and might have no or
      little relationship with cervical cancer. Among the 29 specimens in the normal
      female control group, no viral infection was detected. The correlation of HPV
      with cervical cancer was significantly different between frozen tissues and
      paraffin-embedded tissues. Other viruses such as HSV-2 and CMV are not predictive
      of cervical cancer. They might not be involved in the oncogenic processes
      directly but might enhance the possibility of oncogenesis or infect cancer
      tissues opportunistically.

PMID- 15497010
TI  - Bordetella pertussis infection in northern Taiwan, 1997-2001.
AB  - The clinical presentations of laboratory-confirmed Bordetella pertussis infection
      in Chang Gung Children's Hospital during 1997 and 2001 were analyzed. Of the 46
      cases, 25 (54.3%) were male. The patients ages ranged from 24 days to 37 years,
      with a mean and median of 4.3 years and 10.5 years, respectively. Forty four
      patients had vaccination records, among them 23 patients (52.2%) had received >
      or = 3 doses of pertussis vaccine. Of the patients who were partially vaccinated
      (received 1 or 2 doses vaccine) or unvaccinated, 16 (69.6%) presented with
      whooping cough, 5 (22.2%) with post-tussive vomiting, and 13 (59.1%) with
      cyanosis. Leukocytosis (white blood cells > or = 15,000 cells/microL) and
      lymphocytosis (lymphocytes > or = 10,000 cells/microL) were observed in 17
      (47.2%) and 16 (44.4%) of the patients, respectively. Fourteen patients (30.4%)
      developed complications, among which pneumonia was the most common (92.3%). Among
      infants < or = 1 year of age, 95.2% were partially vaccinated (20/21), compared
      with 5% (1/20) of the patients > 1 year of age (p<0.05). The overall complication
      rate was 37.5%, compared with 18.2% for patients > 1 year of age (p<0.05). One 2
      month-old patient required ventilatory support after the development of
      cardiopulmonary failure. There was no mortality in this study. In summary,
      pertussis most commonly occurred in infants who were unvaccinated or partially
      vaccinated. These patients usually presented with atypical symptoms such as
      cyanosis or apnea. The importance of vaccination still cannot be overemphasized
      because immunized patients usually present with milder disease than those who are
      not immunized.

PMID- 15497011
TI  - Drug resistance of Mycobacterium tuberculosis complex in central Taiwan.
AB  - The prevalence of drug resistance to Mycobacterium tuberculosis complex (MTBC)
      shows marked geographic difference and is the key to determining drugs of choice
      for the initial treatment of tuberculosis (TB). This retrospective study
      investigated the MTBC resistance rate and its contributing factors based on the
      review of medical records from a hospital in central Taiwan. TB culture and
      antimicrobial susceptibility test were performed using the BACTEC MGIT 960
      System. Isoniazid, rifampin, ethambutol and streptomycin were tested. Molecular
      detection of MTBC using BDProbeTec ET kits was conducted in positive culture
      media containing acid-fast bacilli. Between July 2001 and June 2002, 974 (12.4%)
      strains of MTBC were isolated from 7892 clinical specimens from 513 patients.
      They included 348 males and 165 females with mean age of 66.1 +/- 15.6 years and
      63.4 +/- 19.2 years, respectively. Sixty one percent of patients were older than
      64 years of age. The overall resistance rate to 1 or more drugs was 22.4% (n =
      115). The number of strains resistant to individual drugs was 86 (16.8%) to
      isoniazid, 25 (4.9%) to rifampin, 21 (4.1%) to ethambutol, and 63 (12.3%) to
      streptomycin. Twenty (3.9%) isolates were resistant to at least isoniazid and
      rifampin. A history of anti-TB treatment was associated with drug resistance
      (36.8% vs 20.6%, p=0.0056). Only 22 (4.3%) patients were tested for HIV
      antibodies and the results were all negative. The prevalence of resistance to
      anti-TB drugs remains high in Taiwan and is associated with a previous history of
      anti-TB treatment. Retreatment may contribute to an increased prevalence of
      multiple drug resistance.

PMID- 15497012
TI  - Neonatal sepsis in the neonatal intensive care unit: characteristics of early
      versus late onset.
AB  - Neonatal sepsis is a major cause of death in newborns despite sophisticated
      neonatal intensive care. This retrospective study reviewed the clinical
      characteristics of cases of culture-proven sepsis in a neonatal intensive care
      unit from January 1992 to December 2001. Patients were divided into those with
      onset of sepsis in the first 7 days of life (early-onset group) and those with
      onset after the seventh day of life (late-onset group). A total of 270 cases with
      325 episodes of sepsis and 353 isolated pathogens were identified and included in
      the study. The male-to-female ratio was 1.4. The majority of cases of sepsis
      occurred in low birth weight (75.9%) and premature babies (76.7%). Late onset
      occurred in 71.9% of cases. Patients with late onset had a lower mortality rate
      than those with early onset (11.3% vs 28.9%). Coagulase-negative staphylococci
      (20.1%) was the most common organism isolated, but infection with Pseudomonas
      aeruginosa was associated with the highest morality rate (55.0%). Late-onset
      sepsis was significantly more common in very low birth weight and premature
      infants. The most frequently encountered pathogens in the early-onset group were
      group B streptococci (GBS) and Escherichia coli, while in the late-onset group,
      the organisms were coagulase-negative staphylococci and Enterobacteriaceae,
      including E. coli, Klebsiella pneumoniae, and Acinetobacter baumannii. GBS
      infection resulted in the highest mortality when the onset of sepsis was within
      the first 24 hours of life.

PMID- 15497013
TI  - Favorable outcome of infective endocarditis due to Streptococcus agalactiae after
      conservative treatment.
AB  - Infective endocarditis due to Streptococcus agalactiae is uncommon and carries an
      ominous prognosis, leading some authors to advocate early surgery. This report
      describes an 83-year-old woman with community-acquired infective endocarditis due
      to S. agalactiae. The patient, who had a history of surgery for colon cancer,
      presented with fever, agitation and general malaise. She achieved a favorable
      outcome with antibiotic treatment only. For infective endocarditis due to S.
      agalactiae, appropriate antimicrobial agents should be started as soon as
      possible, with surgery reserved for those cases of particular indication.

PMID- 15497014
TI  - Aortic aneurysm in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is frequently associated with cardiovascular
      manifestations, but rarely complicated with aortic disease. We report a 28-year
      old female patient with a 14-year history of SLE and a 3-year history of
      hypertension. She had suffered from palpitation and chest tightness for 1 month
      before admission. Heart echo showed thoracic to low abdominal level with low
      flow. A computed tomography (CT) scan confirmed aneurysms of the descending
      thoracic and upper abdominal aorta, down to the renal level. Diagnosis of aortic
      aneurysm should be considered in patients with SLE, especially those who have a
      history of hypertension, prolonged steroid use, palpitation and chest pain.
      Current imaging modalities, such as cardiac echo, CT and magnetic resonance
      angiography may provide earlier detection of subclinical disease, which may aid
      in preventing these fatal complications. It is important to control hypertension
      aggressively in patients with SLE. In addition to decreasing steroid doses, early
      use of immunosuppressive agents and accurate noninvasive image modalities may
      allow us to prevent severe damage to the aorta and avoid the fatal complications.

PMID- 15497015
TI  - Differentiation of low-molecular-weight heparins: practical implications.

PMID- 15497016
TI  - Anti-Xa and anti-IIa drugs alter international normalized ratio measurements:
      potential problems in the monitoring of oral anticoagulants.
AB  - Several of the newly developed anti-Xa and anti-IIa agents have been shown to
      influence the International Normalized Ratio (INR) values. During phase I trials
      with normal healthy volunteers and phase II study patients who were given
      warfarin and concomitant anti-IIa or anti-Xa agents, it has been reported that
      INR values were falsely elevated. It is of critical importance to know of the
      effects of these agents on INR to avoid dosage errors. To study the influence of
      these agents on INR, we used several anti-IIa agents (argatroban, recombinant
      hirudin, efegatran, and PEG-hirudin) and anti-Xa drugs (pentasaccharides such as
      fondaparinux and idraparinux, DX-9065a and JTV-803). The anti-IIa drugs were
      supplemented in citrated plasma at a concentration of 0 to 1 microg/mL level and
      anti-Xa drugs in the range of 0 to 25 microg/mL. The IC(50) values for each of
      these agents were calculated. Four different commercially available prothrombin
      time (PT) reagents were used to perform the PT assays and to calculate the
      relative INR values. Direct synthetic factor IIa and Xa inhibitors exhibited a
      concentration-dependent increase in the INR values. Hirudin, efegatran, and PEG
      hirudin showed a weaker effect, whereas argatroban showed a much higher elevation
      of the INR values. Synthetic indirect anti-Xa agents such as the pentasaccharide
      did not show any effect on the INR values. Furthermore, prothrombin time reagents
      with high ISI values exhibited disproportionally higher INR values for both the
      direct anti-Xa and anti-IIa agents. Elevation of INR values has therapeutic
      implications when non-oral anticoagulant drugs are used in combination with drugs
      such as warfarin. Because of the false elevation of INR values with some of the
      non-oral anticoagulant drugs, patients who are on concomitant warfarin therapy
      should be carefully evaluated for their corresponding INR values for proper
      dosing. To avoid dosing errors it is best not to use the INR values in the
      therapeutic monitoring of anti-Xa and anti-IIa agents either in the
      monotherapeutic or polytherapeutic modalities. These data also warrant the
      development clinically relevant methods for the monitoring of the concomitant use
      of newly developed anti-Xa and anti-IIa drugs with oral anticoagulants.

PMID- 15497017
TI  - Sapheno-femoral junction pathology: molecular mechanism of saphenous vein
      incompetence.
AB  - A molecular mechanism responsible for varicose vein occurrence was investigated.
      The role of potential cell cycle regulator p21 and programmed cell death in the
      pathology leading to the proximal long saphenous vein (LSV) incompetence was
      investigated. Proximal LSV specimens were obtained from 40 patients with primary
      varicose veins who had undergone crossectomy. The expression of the p21, p53, and
      fas encoding genes was investigated by the means of real-time RT-QPCR.
      Immunostaining for gene product presence, proliferating cell nuclear antigen
      (PCNA), and apoptotic cells (TUNEL assay) was carried out. The results were
      compared to the control healthy vein specimens and correlated with pathologic
      examination findings (of the valve and vein structure). A significant increase in
      p21, p53, and fas mRNA expression were reported in the proximal incompetent
      veins. The expression of p21 correlated with expression of p53 (r = 0.658;
      p<0.05) and negative correlation between media apoptotic index and p21 mRNA
      expression was found (r = -0.493; p<0.05). Decrease in the muscular component
      within the media and disturbances of the local structure in the incompetent LSVs
      were reported. Fas overexpression did not correlate with p53 expression level and
      did not correlate with apoptotic cell number in the respective vein layers. PCNA
      positive cells were present more frequently in the media of the control veins,
      especially in young subjects. Apoptosis downregulation, cell cycle inhibition and
      smooth muscle cell hypertrophy are important factors influencing vein wall
      disturbances related to sapheno-femoral junction incompetence.

PMID- 15497018
TI  - Pregnancy loss, polycystic ovary syndrome, thrombophilia, hypofibrinolysis,
      enoxaparin, metformin.
AB  - Thrombophilia, hypofibrinolysis, and polycystic ovary syndrome (PCOS) are
      associated with recurrent pregnancy loss (RPL) and spontaneous abortion (SAB)
      alone and concurrently. The efficacy and safety of combined enoxaparin-metformin
      was prospectively assessed in women with PCOS with one or more previous SAB,
      thrombophilia, and/or hypofibrinolysis. Twenty-four white women with PCOS were
      studied; 23 with previous pregnancies, seven with RPL of unknown etiology
      (>/=three consecutive pregnancy losses <20 weeks' gestation), two with two
      consecutive SABs, 13 with one SAB, and one with one live birth (HELLP syndrome).
      Prospectively, metformin (1.5 to 2.55 g/day) was administered before and
      throughout gestation, with concurrent enoxaparin (60 mg/day) throughout
      gestation. The 24 cases differed from 93 normal white female controls for the
      factor V Leiden mutation, 17% vs. 2%, Fisher's p [p(f)] = .016, and for the 4G4G
      mutation of the plasminogen activator inhibitor-1 (PAI-1) gene (46% vs. 24%, Chi
      square 4.63, p =. 031). The patients also differed from 44 normal white female
      controls for high levels (> 21.1 U/mL) of the PAI-1 gene product, plasminogen
      activator inhibitor activity (PAI-Fx) (33% vs. 8%, p(f) =. 018), and for high
      factor VIII (>150%) (22% vs. 0%, p(f) = .037). Of the 24 women, 23 had 65
      previous pregnancies without metformin or enoxaparin, with 18 live births, 46 SAB
      (71%), and one elective abortion. On metforminenoxaparin, the same 23 women had
      26 current pregnancies (28 fetuses), with 20 live births, two normal pregnancies
      13 weeks or longer, and six SAB (21%), 3.4-fold lower than previous gestations
      (McNemar's S = 33.6, p <. 0001). There were no adverse maternal or fetal therapy
      effects. Enoxaparin-metformin reduces pregnancy loss in women with PCOS with one
      or more previous SAB, who also have thrombophilia and/or hypofibrinolysis.

PMID- 15497019
TI  - Prevalance of heparin-dependent platelet-activating antibodies in preterm
      newborns after exposure to unfractionated heparin.
AB  - Heparin is frequently used in preterm infants to prolong the patency of
      intravascular catheters. The aim of this study was to evaluate the prevalence of
      heparin-dependent platelet-activating antibodies in newborns. A cross-section of
      all preterm newborn infants expected to require heparin to maintain patency of a
      central venous access line were enrolled. A blood sample was obtained soon after
      birth before heparin exposure to exclude the possibility of placental transfer of
      maternal heparin-dependent platelet-activating antibodies. A second sample was
      obtained at termination of heparin use (mean duration of heparin exposure was 23
      +/- 13 days; range, 6-67). Paired samples, at birth and after heparin use, were
      available for 42 infants with a mean gestational age of 27.8 +/- 2.2 weeks and
      birth weight of 1036 +/- 267 g. Thrombocytopenia developed in 57% (24/42) of the
      infants. None of these infants had clinical suspicion of thrombosis during the
      study period. The etiology of thrombocytopenia was confirmed sepsis in six,
      presumed sepsis in three, necrotizing enterocolitis in one, and unclear in 14
      infants. Anti-heparin/platelet factor 4 antibodies measured using the standard
      assays for heparin-induced thrombocytopenia (two commercially available enzyme
      linked immunosorbent assay tests and the functional platelet serotonin release
      assay) were negative on all infants. Although it could be related to the poor
      ability of these infants to mount an immunologic response, further research is
      necessary to fully understand this lack of response to heparin and to elucidate
      further the reasons for thrombocytopenia in very-low-birth-weight infants.

PMID- 15497020
TI  - Hemostatic abnormalities and changes following bone marrow transplantation.
AB  - Hemostatic parameters were examined in 39 patients who underwent allogeneic bone
      marrow transplantation (BMT). Twenty-six patients survived and 13 patients died
      within 6 months after BMT. The main causes of death were acute graft-versus-host
      disease (GVHD: n=6), veno-occlusive disease (VOD: n=2), and thrombotic
      microangiopathy (TMA: n=2). Plasma levels of D-dimer and thrombomodulin (TM) were
      significantly elevated in the non-survivor group. Plasma levels of soluble fibrin
      (SF) and Fas were significantly elevated in the non-survivor group at 1 to 4
      weeks after BMT. Plasma levels of thrombin-antithrombin complex (TAT), D-dimer,
      and tissue plasminogen activator-plasminogen activator inhibitor-1 complex (tPA
      PAI-1 complex) were significantly elevated in patients with complications after
      BMT. Plasma levels of TAT, D-dimer, and tPA-PAI-1 complex were significantly
      elevated in patients with GVHD. These results suggest that abnormalities of
      hemostatic parameters might predict poor outcomes or complications in patients
      with BMT.

PMID- 15497021
TI  - Thrombosis-free surgical procedures in severe (Homozygote) factor XII deficiency:
      report of four additional cases and literature review.
AB  - The outcome of various surgical procedures carried out in patients with severe
      (homozygote) factor XII deficiency were investigated for the appearance of blood
      coagulation-related complications with particular emphasis on thrombotic
      complications. The surgical procedures were total mastectomy, tonsillectomy and
      adenoidectomy, placement of a hip prosthesis, and double hernia repair. None of
      the patients slowed any complication. Several other reported cases of surgical
      procedures carried out in several patients ware found in the literature. Bleeding
      or thrombotic complications were noted in none of these cases. The surgical
      procedures in some cases were minor such as adenoidectomy, tonsillectomy, or
      nasal polyp removal. However several major surgical procedures were carried out
      in some patients (cholecystectomy, gastrectomy, repair of atrial septal defect,
      coronary bypass). All patients remained asymptomatic. In some cases whole blood
      and/or plasma were used as requested by the caring surgeons. In a few patients,
      the plasma was given prophylactically because of the long partial thromboplastin
      time. Finally, three patients (two for cardiac surgery and one after hip
      replacement) received heparin prophylaxis as foreseen by accepted procedures
      without the undue sequels. These data supply further evidence that factor XII
      deficiency does not only show any bleeding tendency but also can withstand even
      major surgical procedures without thrombotic complications.

PMID- 15497022
TI  - Blood levels of nitric oxide, C-reactive protein, and tumor necrosis factor-alpha
      are upregulated in patients with malignancy-associated hypercoagulable state:
      pathophysiologic implications.
AB  - Endogenous generation of nitric oxide (NO) plays an important role in the
      regulation of cardiovascular and inflammatory responses. This mediator is
      synthesized by a family of enzymes collectively known as NO synthase. Several
      isoforms of this enzyme have been identified and can be grouped as constitutive
      or inducible. Increased production of NO is reported in several inflammatory
      disorders, such as sepsis, arthritis, thrombotic thrombocytopenic purpura (TTP),
      and antiphospholipid syndrome. In addition, NO upregulates cyclo-oxygenase-2 and
      synthesis of several other inflammatory cytokines. Inflammation and thrombotic
      complications are usually associated with malignancy. Earlier reports indicate
      the upregulation of tumor necrosis factor-alpha (TNF-alpha), C-reactive protein
      (CRP), and tissue factor (TF) in patients with malignancy. To determine the
      relationship between inflammatory cytokines and NO in cancer patients with
      hypercoagulable states, baseline plasma samples from 160 patients with confirmed
      malignancy and hypercoagulable state were analyzed for NO levels. A chemical
      method based on a chemiluminescent reaction between NO and ozone using a highly
      sensitive gas phase NO analyzer was used. CRP, TF, and TNF-alpha were measured
      using enzyme-linked immunosorbent assay methods. Of the 160 patients who were
      plasma tested, the baseline NO levels ranged from 13.7 to 98.6 microM (63.1+/
      15.9 microM, mean+/-SD) in contrast to age-matched control, which ranged from 9.1
      to 34.6 microM (19.8+/-6.2 microM, mean+/-SD, n=138). Cancer patients also showed
      marked variations in the NO levels. Eighteen of 60 cancer patients exhibited
      greater than 60 microM NO levels. The CRP, TNF-alpha and TF were also
      significantly elevated. A correlation between CRP (r(2)=0.73) and NO levels was
      noted in cancer patients with hypercoagulable state. These data suggest that the
      pathogenesis associated with malignancy/hypercoagulable state is associated with
      an inflammatory component. In addition, the observed hemodynamic changes in some
      of the cancer patients may be due to increased NO production.

PMID- 15497023
TI  - Ramifications of four concurrent thrombophilic mutations and one hypofibrinolytic
      mutation.
AB  - A kindred was examined in which the 48-year-old white female proband with three
      deep venous thrombosis-pulmonary emboli events had four thrombophilic and one
      hypofibrinolytic mutations, and in which her 14-year-old asymptomatic daughter
      had four thrombophilic mutations. The proband was heterozygous for the G1691A
      factor V Leiden, G20210A prothrombin, and platelet glycoprotein IIIa PL A1/A2
      mutations, had high factor VIII (221%), and was homozygous for the 4G4G
      plasminogen activator inhibitor-1 gene mutation, with high plasminogen activator
      inhibitor activity (23.7 U/mL). Her 14-year-old daughter was homozygous for the
      G1691A factor V Leiden and platelet glycoprotein IIb-IIIa PL A2/A2 mutations,
      compound heterozygous for the C677T and A1298C methylenetetrahydrofolate
      reductase (MTHFR) mutations, and heterozygous for the G20210A prothrombin
      mutation, a combination with an estimated likelihood of 1.6 x 10(-7). In 247
      white healthy controls, there was no V Leiden homozygosity and no V Leiden
      prothrombin gene compound heterozygosity. Heterozygosity for the V Leiden and
      prothrombin gene mutations was 3.2% and 4.1%, respectively. Homozygosity for the
      platelet glycoprotein IIb-IIIa PL A2A2, PAI-1 gene 4G4G, and C677T MTHFR
      mutations was 3.2%, 22.7%, and 12%, respectively. The proband will receive
      anticoagulation therapy for life. Beyond aspirin, avoidance of exogenous
      estrogens, and enoxaparin prophylaxis during pregnancy, it is not known whether
      the proband's daughter should have lifelong anticoagulation therapy, or only
      after her first thrombotic event.

PMID- 15497024
TI  - Prevention of venous thrombosis and thrombophlebitis in long-haul flights with
      pycnogenol.
AB  - The aim of this study was to evaluate the occurrence of deep venous thrombosis
      (DVT) and superficial vein thrombosis (SVT) and its prophylaxis with an oral anti
      edema and antithrombotic agent (Pycnogenol, Horphag, Research Management SA,
      Geneva, Switzerland) in long-haul flights, in subjects at moderate to high-risk
      of DVT and SVT. The study pre-included 244 pre-selected subjects; 211 were
      included (33 were excluded for several reasons due to logistic problems) and 198
      completed the study; 13 subjects were lost for follow-up at the end of the
      flight, all for non-medical problems (i.e., for difficult connections). All
      subjects were scanned within 90 minutes before the flight and within 2 hours
      after disembarking. Subjects were supplemented with 100 mg Pycnogenol per
      capsule. Treatment subjects received two capsules between 2 and 3 hours before
      flights with 250 mL of water; two capsules were taken 6 hours later with 250 mL
      of water and one capsule the next day. The control group received comparable
      placebo at the same intervals. The flight duration was on average 8 hours and 15
      minutes (SD 55 min) (range, 7.45-12.33). In the control group there were five
      thrombotic events (one DVT and four superficial thromboses) while only
      nonthrombotic, localized phlebitis was observed in the Pycnogenol group (5.15%
      vs. no events; p<0.025). The ITT (intention to treat) analysis detects 13
      failures in the control group (eight lost to follow up + five thrombotic events)
      of 105 subjects (12.4%) vs. five failures (4.7%; all lost, no thrombotic events)
      in the treatment group (p<0.025). No unwanted effects were observed. In
      conclusion, this study indicates that Pycnogenol treatment was effective in
      decreasing the number of thrombotic events (DVT and SVT) in moderate-to-high risk
      subjects, during long-haul flights.

PMID- 15497025
TI  - Tissue factor pathway inhibitor and thrombin activatable fibrinolytic inhibitor
      plasma levels following burn and septic injuries in rats.
AB  - Burn and septic injuries induce profound changes in coagulation status. This
      study examined the changes in plasma tissue factor pathway inhibitor (TFPI) and
      thrombin activatable fibrinolytic inhibitor (TAFI) levels in a rat model of burn
      and septic injuries. Rats underwent 30% TBSA cutaneous scald burn injury and
      septic insult was induced by caecal ligation and puncture (CLP). CLP was
      superimposed on burn injury to mimic the clinical model of sepsis complicating
      burn injury. Rats were pretreated with Cprofloxacin orally to colonize their gut
      with Enterococcus faecalis. TFPI and TAFI plasma levels were measured using
      functional activity assay kit with a chromogenic method at 24 and 72 hours
      following the injuries. TFPI levels decreased significantly at 24 hours in burn,
      CLP, and burn+CLP groups, followed by incomplete rebound recovery at 72 hours in
      all three groups. On the other hand, TAFI levels increased significantly at 24-
      and 72-hour time points in all three groups. These results suggest that burn,
      septic, and their combined injuries perturb coagulation cascade and thrombotic
      process toward the procoagulant pathway by impairing fibrinolysis.

PMID- 15497026
TI  - Iron deficiency and thrombosis: literature review.
AB  - Compared to primary thrombocytosis such as that caused by essential
      thrombocytosis, reactive thrombocytosis is generally regarded as benign. However,
      reactive thrombocytosis has infrequently been reported to cause severe and even
      fatal complications. Two fatal cases of reactive thrombocytosis and iron
      deficiency anemia associated with peripheral/pulmonary vascular and
      cerebrovascular thrombosis are described. The literature on thrombosis and
      reactive thrombocytosis associated with iron deficiency anemia is reviewed.

PMID- 15497027
TI  - Antiphospholipid syndrome associated with malignant mesothelioma presenting with
      superior vena cava thrombosis: a case report.
AB  - A 59-year-old woman who had dyspnea and neck swelling for 10 days was admitted to
      the hospital. Malignant peritoneal mesothelioma was diagnosed previously.
      According to the clinical findings, and laboratory and pathologic examination,
      the patient was found to have disseminated venous thrombosis and antiphospholipid
      syndrome, which is treatment-resistant autoimmune paraneoplastic syndrome.

PMID- 15497028
TI  - Bleeding and other presentations in Thai patients with dengue infection.
AB  - Dengue infection is a major public health problem, affecting the general
      population in Southeast Asia. Hematologic aberrations in dengue infection include
      atypical lymphocytosis, coagulopathy, and predominant thrombocytopenia. Bleeding
      and other presentations in 30 Thai patients with dengue infection during an
      endemic season (2003) are presented. A review of the clinical presentation of
      these patients was performed. All had fever as a chief complaint. The three most
      common complaints were fever (100%), vomiting (90%), and cough (90%),
      respectively. Concerning bleeding, only eight cases (26.6%) had signs of
      bleeding. Those manifestations included petechiae (seven cases, 23.3%) and melena
      (one case, 3.3%). Skin bleeding (petechiae) due to thrombocytopenia is the most
      common bleeding manifestation in dengue infection. However, physicians should not
      overlook bleeding from other less common sites such as the gastrointestinal tract
      and genitourinary tract.

PMID- 15497029
TI  - The importance of platelet counts in dengue infection: 35 cases and literature
      review.
AB  - Dengue infection is a major vector-borne disease. The classical form of this
      infection has an incubation period of 5 to 8 days followed by fever, violent
      headache, and chills, with rash developing after 3 to 4 days. A summative report
      on the platelet count and its clinical correlation to duration of fever in 35
      Thai children is presented. Most of the subjects visited to the physician with a
      complaint for fever. Most patients went to see the physician between the 3rd and
      the 5th day from the onset of fever. There is no significant correlation between
      platelet count and duration of fever (ANOVA test, p = 0.28). However, there is a
      trend of increase platelet count in the later days. In addition, an overview on
      the previous literatures on platelet count and dengue infection is presented.

PMID- 15497030
TI  - Endothelial injury markers with high-dose intravenous iron therapy in renal
      failure.
AB  - Endothelial injury is prevalent in patients with chronic renal failure (CRF) and
      may be exacerbated by commonly used intravenous (IV) iron therapy. The effects of
      high-dose IV iron sucrose treatment (200 mg daily in 250 mL of 0.9% saline,
      administered over 1 hour, median treatment duration 5 days) on circulating
      endothelium and/or tissue injury markers such as hepatocyte growth factor,
      thrombomodulin, von Willebrand factor, and C-reactive protein levels were
      studied. The markers were determined in 24 anemic (mean hemoglobin 9.48 g/dL) pre
      dialysis (median creatinine clearance 21.5 mL/min) patients with CRF and defined
      absolute and/or functional iron deficiency. The measurements were performed
      before iron administration and 24 hours after the last infusion. All the markers
      remained unchanged following the IV iron therapy (all p < 0.172); no thrombotic
      or other adverse effects were observed. In conclusion, the above high-dose IV
      iron sucrose supplementation does not cause evident endothelial or other tissue
      injury in patients with CRF, and is clinically safe.

PMID- 15497032
TI  - Hearing AIDS and music.
AB  - Historically, the primary concern for hearing aid design and fitting is
      optimization for speech inputs. However, increasingly other types of inputs are
      being investigated and this is certainly the case for music. Whether the hearing
      aid wearer is a musician or merely someone who likes to listen to music, the
      electronic and electro-acoustic parameters described can be optimized for music
      as well as for speech. That is, a hearing aid optimally set for music can be
      optimally set for speech, even though the converse is not necessarily true.
      Similarities and differences between speech and music as inputs to a hearing aid
      are described. Many of these lead to the specification of a set of optimal
      electro-acoustic characteristics. Parameters such as the peak input-limiting
      level, compression issues-both compression ratio and knee-points-and number of
      channels all can deleteriously affect music perception through hearing aids. In
      other cases, it is not clear how to set other parameters such as noise reduction
      and feedback control mechanisms. Regardless of the existence of a "music
      program,'' unless the various electro-acoustic parameters are available in a
      hearing aid, music fidelity will almost always be less than optimal. There are
      many unanswered questions and hypotheses in this area. Future research by
      engineers, researchers, clinicians, and musicians will aid in the clarification
      of these questions and their ultimate solutions.

PMID- 15497034
TI  - [Regulation of G protein-coupled receptor kinase 5 mRNA and protein level in rat
      brain by addictive drugs].
AB  - G protein-coupled receptor kinase 5 (GRK5) plays an important role in the
      regulation of GPCR-transduced signals. Our previous study showed that acute
      administration of morphine could significantly increase GRK5 mRNA level in the
      cerebral cortex and hippocampus of the rat brain. The current study investigated
      the potential effects of acute administration of addictive drugs including
      morphine, heroine and cocaine on GRK5 mRNA level in the rat brain using in situ
      hybridization and analyzed the effects of acute and chronic morphine treatments
      on GRK5 protein level in the rat brain using Western blotting assay. Our results
      showed that 2 h after the initial morphine (10 mg/kg), cocaine (15 mg/kg) and
      heroine (1 mg/kg) treatment, the mRNA level of GRK5 in the parietal cortex
      increased about 110% (P<0.01), 70% (P<0.05) and 100% (P<0.01), respectively. In
      the temporal cortex, GRK5 mRNA level increased about 90% (P<0.01), 40% (P<0.05)
      and 80.0% (P<0.01), respectively . In the hippocampus, the mRNA level of GRK5
      increased about 60% (P<0.01), 30% (P<0.05) and 80% (P<0.01). However, the mRNA
      level of GRK5 remained unchanged after acute morphine, cocaine or heroine
      treatment. In the cerebral cortex of the rat brain, the acute administration of
      morphine (NS-Mor) increased GRK5 protein level by about 60% while the chronic
      morphine treatment (Mor-Mor) increased GRK5 protein level even higher [about 130%
      compared with the control group (chronic saline treatment, NS-NS) group, P<0.01].
      In the hippocampus, GRK5 protein level remained unchanged after acute
      administration of morphine (P>0.1),while the level of GRK5 protein tended to
      decrease after chronic morphine treatment (P=0.098). In the thalamus, acute
      morphine treatment caused no change in GRK5 protein level (P>0.1) while after
      chronic morphine treatment, GRK5 protein level decreased significantly (more than
      90%, P<0.01), Taken together, our results indicate that addictive drugs can
      regulate GRK5 in the rat brain on protein level as well as on mRNA level and
      suggest that GRK5 may play a role in addiction of psychoactive substances.

PMID- 15497033
TI  - Music perception with cochlear implants: a review.
AB  - The acceptance of cochlear implantation as an effective and safe treatment for
      deafness has increased steadily over the past quarter century. The earliest
      devices were the first implanted prostheses found to be successful in
      compensating partially for lost sensory function by direct electrical stimulation
      of nerves. Initially, the main intention was to provide limited auditory
      sensations to people with profound or total sensorineural hearing impairment in
      both ears. Although the first cochlear implants aimed to provide patients with
      little more than awareness of environmental sounds and some cues to assist visual
      speech-reading, the technology has advanced rapidly. Currently, most people with
      modern cochlear implant systems can understand speech using the device alone, at
      least in favorable listening conditions. In recent years, an increasing research
      effort has been directed towards implant users' perception of nonspeech sounds,
      especially music. This paper reviews that research, discusses the published
      experimental results in terms of both psychophysical observations and device
      function, and concludes with some practical suggestions about how perception of
      music might be enhanced for implant recipients in the future. The most
      significant findings of past research are: (1) On average, implant users perceive
      rhythm about as well as listeners with normal hearing; (2) Even with technically
      sophisticated multiple-channel sound processors, recognition of melodies,
      especially without rhythmic or verbal cues, is poor, with performance at little
      better than chance levels for many implant users; (3) Perception of timbre, which
      is usually evaluated by experimental procedures that require subjects to identify
      musical instrument sounds, is generally unsatisfactory; (4) Implant users tend to
      rate the quality of musical sounds as less pleasant than listeners with normal
      hearing; (5) Auditory training programs that have been devised specifically to
      provide implant users with structured musical listening experience may improve
      the subjective acceptability of music that is heard through a prosthesis; (6)
      Pitch perception might be improved by designing innovative sound processors that
      use both temporal and spatial patterns of electric stimulation more effectively
      and precisely to overcome the inherent limitations of signal coding in existing
      implant systems; (7) For the growing population of implant recipients who have
      usable acoustic hearing, at least for low-frequency sounds, perception of music
      is likely to be much better with combined acoustic and electric stimulation than
      is typical for deaf people who rely solely on the hearing provided by their
      prostheses.

PMID- 15497035
TI  - [Identification of a novel mutation at the point of low density lipoprotein
      receptor gene from a subject with familial hypercholesterolemia].
AB  - Family hypercholesterolemia (FH) is a genetic disorder caused by mutation in the
      low density lipoprotein receptor (LDLR) gene. It is characterized by a high
      concentration of low density lipoprotein (LDL), which frequently gives rise to
      tendon xanthenes and premature coronary artery disease. We studied a FH family
      ,which was diagnosed by clinical features and blood lipid tests. The Total
      cholesterol level of the family was 19.05 mmol/L and the LDL level was 17.06
      mmol/L in the proband homozygous FH subjects, while the total cholesterol was
      7.96 mmol/L and LDL was 5.55 mmol/L in the heterozygous FH subjects. DNA segments
      amplified with PCR were sequenced in heterozygous and homozygous FH patients. Two
      novel identical mutation alleles of GAG683GCG, which caused an amino acid change
      from Glu to Ala, were detected in Exon4 of LDL receptor gene in homozygous
      proband. DNA sequencing revealed that the proband's parents were heterozygotes
      with the same mutational alleles as the proband. These results are in coincidence
      with the clinical diagnoses. Moreover Epstein-Barr virus transformed lymphocytes
      (EBV-Ls) were derived by routine virus infection transforming protocol. The cells
      bounded with the fluorescently conjugated LDL were measured by fluorescence flow
      cytometry. The ratios of functional LDLR in EBV-Ls originated from homozygous FH,
      heterozygous FH and normal control were 7.02%, 62.64% and 84.69%, respectively.
      As a result, the homozygous FH patient's LDLR had 8.29% and the heterozygous FH
      patient's LDLR had 73.96% of the activity of the control. It is apparent that LDL
      receptor activity of homozygous FH subject is significantly lower than normal
      control. The data from fluorescence flow cytometry analysis of EBV-Ls strongly
      support the clinical diagnoses and the results of DNA sequencing. In accordance
      with the updated version of UMD-LDLR, the mutant GAG683GCG in Exon4 of LDLR gene
      which we have identified is a novel mutation of the LDLR gene in human with
      hypercholesterolemia.

PMID- 15497036
TI  - Effect of chronic cigarette smoking on large-conductance calcium-activated
      potassium channel and Kv1.5 expression in bronchial smooth muscle cells of rats.
AB  - To investigate the role of potassium channels in the pathogenesis of airway
      hyperresponsiveness induced by cigarette smoking, the alteration in expression of
      large-conductance calcium-activated potassium channel (BKca) and voltage
      dependent delayed rectifier potassium channel (Kv1.5) in bronchial smooth muscle
      cells were investigated in chronic cigarette smoking rats. Airway responsiveness
      was determined, hematoxylin and eosin staining, immuno-histochemistry, in-situ
      hybridization and western blot techniques were used. The results showed: (1)
      Chronic cigarette smoking down-regulated the protein synthesis and mRNA
      expression of BKca and Kv1.5 in bronchial and bronchiolar smooth muscles. (2)
      BKca decreased more markedly than Kv1.5 in bronchi, but there was no difference
      between them in bronchioli. (3) No changes in the expression of these two
      potassium channel proteins were found in extracted cell membrane protein from
      lung tissue. The results suggest that chronic cigarette smoking can down-regulate
      the levels of BKca and Kv1.5 in rat bronchial smooth muscle cells in vivo, which
      might contribute to the mechanism of airway hyperresponsiveness induced by
      cigarette smoking.

PMID- 15497037
TI  - [Dynamic changes of heme oxygenase-1 protein and mRNA in the brains of rats with
      experimental allergic encephalomyelitis].
AB  - In order to investigate the role of heme oxygenase-1 (HO-1) in the molecular
      mechanism of experimental allergic encephalomyelitis (EAE), which was induced by
      guinea pig spinal cord homogenate + complete freund adjuvant on Wistar rats, we
      observed the gene of HO-1 and its protein expression with reverse transcriptase
      polymerase chain reaction(RT-PCR) and immunohistochemistry 1, 7, 14, and 21 d
      after EAE induction in rats. The relationship between HO-1 and the symptoms of
      EAE was also observed. The results showed that the levels of HO-1 mRNA and its
      protein expression were very low in the brains of the control group, whereas they
      were enhanced gradually with pathological course in the brain and onsets of
      symptoms, signs of EAE. On day 7, the level of HO-1 mRNA reached the peak, but
      the expression level of HO-1 protein in the brains reached the peak on day 14.
      The immunoreactive cells of HO-1 were mainly located at the choroid plexuses and
      subfornical organ (SFO), as well as in regions around the "sleeve-like" lesion
      foci, all of which were coincident with the locations of lesions of EAE. The
      levels of HO-1 mRNA and its protein expression were lowered gradually on day 21,
      which were in parallel with the severities of symptoms and signs of EAE. After a
      specific inhibitor of HO-1, Snpp-9, was applied, both of the symptoms and
      pathological lesions of EAE in the rat brains were mitigated markedly. Therefore,
      these results may suggest that the dynamic changes of HO-1 mRNA and its protein
      expression are in parallel with the changes of symptoms and pathological lesions
      of EAE in the brain. In conclusion, the levels of HO-1 mRNA and its protein
      expression in brains may play an important role in the pathogenesis of EAE, and
      application of inhibitors of HO-1 may be one of the potential therapeutic ways
      for the prevention and treatment of EAE.

PMID- 15497038
TI  - Somatic and visceral nociceptive inputs from the orofacial area and the upper
      alimentary tract converge onto CB-containing neurons in interstitial nucleus of
      the spinal trigeminal tract in rats.
AB  - The interstitial nucleus of the spinal trigeminal tract (INV) contains many
      calbindin-D28k-containing neurons (CB-neurons) receiving convergence information
      from the somatic and visceral structures. The purpose of the present study was to
      confirm whether the primary afferent terminals from the inferior alveolar nerve
      (IAN) make close contact and synaptic connections with the same CB-neurons
      receiving visceral nociceptive signals in INV. Biotinylated dextran amine (BDA)
      and horseradish peroxidase (HRP) tracing combined with CB and Fos proteins
      immunohistochemistry were used. After injections of BDA and formalin into
      unilateral IAN and upper alimentary tract, respectively, the transganglionic
      labeled afferent fibers and terminals from IAN were observed in the ipsilateral
      INV, especially in its enlarged part. A large number of CB- and Fos-like
      immunoreactive (LI) neurons were found in bilateral INV. These CB- and Fos-LI
      neurons mostly overlapped with BDA-labeled terminals in the enlarged part of INV.
      About one half of the CB-LI neurons were double labeled with Fos-LI nuclei
      (74/153). The terminals from IAN were to made close contacts with many CB/Fos
      double labeled or CB-single labeled neurons. After injection of HRP into IAN, HRP
      labeled fibers and terminals in INV were similar to that labeled with BDA. Under
      the electron microscope, a large number of CB-LI dendrites and a few soma in the
      enlarged part of INV were found to form asymmetrical axo-dendritic and axo-somal
      synapses with the HRP-labeled axon terminals. These results indicate that the
      orofacial somatic inputs from IAN and the visceral nociceptive inputs from the
      upper alimentary tract converge onto the same CB-containing neurons in INV. These
      CB-containing neurons in INV probably play an important role in information
      integration as well as visceral and cardiovascular activity.

PMID- 15497039
TI  - Acute nerve injury induces long-term potentiation of C-fiber evoked field
      potentials in spinal dorsal horn of intact rat.
AB  - Nerve injury produces a long lasting neuropathic pain, manifested as allodynia, a
      decrease in pain threshold and hyperalgesia, an increase in response to noxious
      stimuli. The mechanism underlying the lasting abnormal pain is not well
      understood. Our previous works have shown that electrical tetanic stimulation of
      the sciatic nerve induces long-term potentiation (LTP) of C-fiber evoked field
      potentials in the spinal dorsal horn, which is considered as a synaptic model of
      pathological pain. In the present study we tested if nerve injury, which is
      proved to produce neuropathic pain, induced the spinal LTP in intact rats. C
      fiber evoked field potentials in spinal dorsal horn produced by electrical
      stimulation (10-20 V, 0.5 ms, 1/min) of the sciatic nerve were recorded. For
      induction of LTP of C-fiber evoked field potentials, three types of noxious
      stimuli were applied. (1) Electrical tetanic stimulation (40 V, 0.5 ms pulses at
      100 Hz for 1 s repeated four times at 10 s intervals). (2) Transection of the
      sciatic nerve at 4-5 mm distal to the stimulation electrode. (3) Crushing the
      sciatic nerve with a forceps four times at 4-5 mm distal to stimulation electrode
      (from distal to proximal with 1 mm spacing at 10 s intervals), which simulated
      electrical tetanic stimulation. Acute nerve injury was made by either transection
      of the sciatic nerve at the distal to the stimulating electrode or crushing the
      sciatic nerve. We found that nerve injury by cutting or crushing the sciatic
      nerve produced LTP of C-fiber evoked field potentials lasting until the end of
      the experiments (3-9 h), and that pretreatment of the sciatic nerve with
      lidocaine 10 min prior to the nerve transectoin completely blocked LTP induced by
      nerve transection. The nerve transection-induced LTP was blocked by NMDA receptor
      antagonist AP5. LTP produced by nerve transection could not be further
      potentiated by electrical tetanic stimulation, while LTP induced by single
      electrical tetanic stimulation could be further potentiated by transection of the
      sciatic nerve. However, when LTP was saturated by several times of electrical
      tetanic stimulation, nerve transection did not affect the spinal LTP. We conclude
      that acute nerve injury induces LTP of C-fiber evoked field potentials in intact
      animals and that nerve transection is more powerful than electrical tetanic
      stimulation for induction of the spinal LTP. The results further support the
      notion that LTP of C-fiber evoked field potentials may underlie neuropathic pain.

PMID- 15497040
TI  - [Changes of discharge rate and pattern of 5-hydroxytrypamine neurons of dorsal
      raphe nucleus in a rat model of Parkinson's disease].
AB  - In the present study, changes of the neuronal activity of 5-hydroxytrypamine (5
      HT) neurons of dorsal raphe nucleus(DRN) in a rat model of Parkinson's disease
      (PD) were investigated with glass microelectrode recording. The results showed
      that the discharge rates of 5-HT neurons in control and PD rats were (1.61+/
      0.56) Hz and (2.61+/-1.97) Hz, respectively. The discharge rate of PD rats was
      significantly increased when compared to that of the control rats. In control
      rats, 79% of 5-HT neurons discharged regularly and 21% in bursts. In PD rats,
      however, 36% of 5-HT neurons discharged regularly, 16% irregularly and 47% in
      bursts. The percentage of 5-HT neurons discharging in bursts was obviously higher
      than that of the control rats (P<0.05). The data suggest that the discharge rate
      and bursting pattern of 5-HT neurons in DRN are increased in a rat model of
      Parkinson's disease.

PMID- 15497041
TI  - [Nitric oxide increases persistent sodium current of ventricular myocytes in
      guinea pig during normoxia and hypoxia].
AB  - Whole cell patch-clamp technique was used to record the changes of persistent
      sodium current (I(Na.P)) and the effect of administered agents in ventricular
      myocytes of guinea pig to investigate the essence of I(Na.P) and mechanism of
      increased I(Na.P) of ventricular myocytes during hypoxia. The results showed: (1)
      Pro-NO L-arginine(L-Arg) and donor sodium nitroprusside (SNP) increased I(Na.P)
      in a concentration-dependent manner in normoxia. (2) I(Na.P) increased gradually
      with the prolongation of hypoxia time. After 15 min of hypoxia, administration of
      N(G)-nitro-L-arginine methyl ester (L-NAME), a NO synthase inhibitor, could not
      significantly recover the increased I(Na.P) [(1.344+/-0.320) vs (1.301+/-0.317)
      pA/pF, P>0.05, n=5]; (3) During hypoxia the perfusion solution with L-NAME
      decreased the increased I(Na.P), and the difference was significant compared with
      pure hypoxia [(0.914+/-0.263), n=5 vs (1.344+/-0.320) pA/pF, P<0.05, n=6],
      whereas the amplitude of I(Na.P) was still larger than that in normoxia [(0.914+/
      0.263) vs (0.497+/-0.149) pA/pF, P<0.05, n=5]; (4) Reducing agent dithiothreitiol
      (DTT) not only recovered the increased I(Na.P) by L-Arg and administered SNP
      after hypoxia [(1.449+/-0.522) vs (0.414+/-0.067) pA/pF, P<0.01, n=6, and
      (1.786+/-0.636) vs (0.436+/-0.141) pA/pF, P<0.01, n=5, respectively], but also
      decreased the I(Na.P) in normoxia [(0.442+/-0.056) vs (0.396+/-0.057) pA/pF,
      P<0.01, n=6]. Our results suggest that hypoxia increases I(Na.P) of ventricular
      myocytes, which is induced by raised NO oxidating sodium channel protein in
      myocardial membrane during hypoxia. The activity of I(Na.P) in normoxia is
      related to the oxidation state of the channel protein.

PMID- 15497042
TI  - [Role of hypoxia-inducible factor-1alpha in the prevention of cardiomyocyte
      injury induced by hypoxic preconditioning].
AB  - In order to understand the intracellular mechanism of preconditioning, we
      investigated the relationship among activities of extracellular signal-regulated
      protein kinases (ERKs), the expression of hypoxia-inducible factor -1alpha (HIF
      1alpha) and the effect of hypoxic preconditioning (HPC) on cell injury induced by
      hypoxia-reoxygenation in cultured neonatal rat cardiomyocytes 24 h after brief
      hypoxia. Cultured cardiomyocytes of neonatal Sprague-Dawley rats were divided
      into four groups: hypoxia/reoxygenation (H/R), hypoxia preconditioning (HPC),
      hypoxia preconditioning + mitogen-activated protein kinase (MAPK) inhibitor
      PD98059 (HPC+PD98059), and control (C). We measured the survival rate and
      apoptosis rate of cardiomyocytes at 6 or 12 h after hypoxia/reoxygenation,
      activities of extracellular signal-regulated protein kinases (ERKs), and
      expression of hypoxia-inducible factor-1alpha (HIF-1alpha). We found that the
      survival rate of cardiomyocytes in hypoxic preconditioning group increased by
      6.08% and 7.91% at 6 and 12 h after hypoxia/reoxygenation (n=6, P<0.05),
      respectively, and the apoptotic rate decreased by 10.92% and 14.34% (n=6, P<0.05)
      respectively. Hypoxic preconditioning increased the abundance of phospho-ERK1/2
      by 3-folds and expression of HIF-1alpha by 1-fold in whole cell extracts from
      hypoxic preconditioned cardiomyocytes. PD98059, an inhibitor of the upstream
      kinase of ERKs, abolished the anti-injury effect, ERKs activation, and expression
      of HIF-1alpha induced by hypoxic preconditioning. Statistical analysis indicated
      that there was negative correlation between apoptotic rate and activities of ERKs
      or expression of HIF-1alpha, and positive correlation between activities of ERKs
      and expression of HIF-1alpha. It is concluded that hypoxic preconditioning
      protects cardiomyocytes from hypoxia/reoxygenation-induced injury and that
      upregulation of HIF-1alpha through ERKs pathway mediates the cardioprotection of
      hypoxic preconditioning.

PMID- 15497043
TI  - [Chronic multiple stress enhances learning and memory capability in rats].
AB  - The present study aimed at investigating the effects of chronic multiple stress
      on learning and memory functions of rats. Adult male Wistar rats were randomly
      divided into stressed and control groups. Rats in the stressed group were
      irregularly and alternately exposed to the situation of vertical revolution,
      sleep deprivation, noise stimulation, and night illumination 6 h per day for 6
      weeks to prepare a chronic multiple stressed model. Learning and memory
      performance of rats was measured by using Morris water maze first and Y-maze
      afterwards. Neurons in the dentate gyrus(DG), CA3 and CA1 regions of the
      hippocampus were stained by using Cresyl violet method and counted. The results
      showed that: (1) After chronic multiple stress, compared with the control rats,
      the escape latency to the hidden platform in Morris water maze was significantly
      shortened in stressed rats. In stressed and control groups, the escape latency
      periods were (15.89+/-9.15) s and (27.30+/-12.51) s, respectively, indicating
      that spatial memory of the stressed rats was stronger than that of the control
      ones. In brightness-darkness discrimination learning in the Y- maze, the correct
      trials and correct percentage of entering safe arm was remarkably increased in
      the stressed rats, the correct rates of stressed and control groups were (79.01+/
      1.23)% and (66.12+/-1.61)%, respectively, indicating that brightness-darkness
      discrimination learning ability of the stressed rats was better than that of the
      control ones. (2) After chronic multiple stress, nerve cell density in DG, CA1
      and CA3 of the hippocampus in stressed rats was higher than that of the control
      group, the cell densities in DG, CA1 and CA3 of the stressed and the control
      group were (223.78+/-26.52), (112.07+/-14.23) and (105.55+/-18.12) as well as
      (199.13+/-15.36), (92.89+/-13.69), and (89.02+/-15.77) respectively. These
      results suggest that the chronic multiple stress may enhance the capability of
      spatial memory and brightness-darkness discrimination learning of rats. Possible
      reasons for the chronic multiple stress-induced learning and memory enhancement
      of rats were also discussed.

PMID- 15497044
TI  - High-frequency electrical stimulation of femoral nerve reduces infarct size
      following myocardial ischemia-reperfusion in rats.
AB  - The effects of femoral nerve electrostimulation (FNES) on ischemia-reperfused
      myocardium were examined in the urethane- anesthetized rats to determine whether
      FNES may provide cardioprotection and to observe the possible mechanism. The area
      at risk (AR) and infarct area (IA) were determined using Evans blue and nitro
      blue tetrazolium staining, respectively. Infarct size (IS) was defined as
      100xIA/AR (%). The results are as follows: (1) During 30 min myocardial ischemia
      and subsequent 120 min reperfusion, the myocardial infarct size occupied (54.96+/
      0.82)% of the area at risk. (2) FNES of high frequency (10 V, 100 Hz, 1 ms)
      significantly reduced myocardial infarct size to (36.94+/-1.34)% (P<0.01),
      indicating the cardioprotective effect FNES of high frequency on myocardial
      ischemia-reperfusion, while FNES of low frequency (10 V, 10 Hz, 1 ms) had no
      effect on myocardial infarct size. (3) Pretreatment with either naloxone (5 mg
      /kg, i.v), a nonselective opioid receptor antagonist, or glibenclamide (5 mg /kg,
      i.v), a K(ATP) channel antagonist, completely abolished the cardioprotection of
      FNES (100 Hz) from myocardial ischemia-reperfusion. It is suggested that FNES of
      high frequency can protect myocardium from ischemia-reperfusion injury. The
      possible mechanism is that FNES of high frequency may induce the release of
      opioids from the central nervous system, and the activation of opioid receptors
      in the heart results in an opening of myocardial K(ATP) channels which can
      protect myocardium.

PMID- 15497045
TI  - [Chronic intermittent hypoxia decreases acute hypoxic inhibition of voltage-gated
      potassium channel in rat pulmonary arterial smooth muscle cells].
AB  - For determination the ionic mechanisms of the hypoxic acclimatization at the
      level of channels, male Spradue-Dawley rats were divided into two groups: control
      normoxic group and chronic intermittent hypoxic group [O2 concentration: (10 +/
      0.5)%, hypoxia 8 h a day]. Using whole cell patch-clamp technique, voltage-gated
      potassium channel currents (IK(V)) were recorded in freshly isolated pulmonary
      arterial smooth muscle cells (PASMCs) of rat with acute isolated method. The
      effect of acute hypoxia on IK(V) of PASMCs from chronic intermittent hypoxia
      group was investigated to offer some basic data for clarifying the ionic
      mechanisms of the hypoxic acclimatization. The results showed: (1) In control
      normoxic group, after acute hypoxia free-Ca(2+) solution, the resting membrane
      potential (Em) of PASMCs was depolarized significantly from -47.2+/-2.6 mV to 
      26.7+/-1.2 mV, and the IK(V) of PASMCs was decreased significantly from 153.4+/
      9.5 pA/pF to 70.1+/-0.6 pA/pF, the peak current percent inhibition was up to
      (57.6+/-3.3)% at +60 mV, and current-voltage relationship curve shifted to the
      right. (2) In chronic intermittent hypoxic group, the IK(V) of PASMCs was
      decreased significantly by exposure to intermittent hypoxia in a time-dependent
      manner, appeared to start on day 10 and continued to day 30 (the longest time
      tested) of hypoxia, and current-voltage relationship curve shifted to the right
      in a time-dependent manner. (3) Compared with the control normoxic group, the
      percent IK(V) inhibition by acute hypoxia was significantly attenuated in the
      chronic intermittent hypoxia group and this inhibition effect declined with time
      exposure to hypoxia. The results suggest that K(V) inhibition was significantly
      attenuated by chronic intermittent hypoxia, and this effect may be a critical
      mechanism of the body hypoxic acclimatization.

PMID- 15497046
TI  - [The protective effect of diazoxide on long-term heart preservation].
AB  - Prolongation of the duration of heart preservation in vitro is very important in
      clinical heart transplantation. Previous studies have shown that mitochondrial
      ATP-sensitive potassium channel (mitoK(ATP)) plays an important role in
      cardioprotective effect. The purpose of this study was to assess whether the
      mitoK(ATP) opener diazoxide as an additive to cardioplegia solution could enhance
      myocardial protection during long-term hypothermic preservation of the rat heart.
      Langendorff model of isolated rat heart was used. After 30 min stabilization of
      perfusion, the hearts were stored in Celsior cardioplegia solution at 4 degrees C
      with (15, 30 and 45 micromol/L) or without diazoxide, a mitoK(ATP) channel
      opener, for 10 h followed by 60 min reperfusion. The recovery of cardiac
      contractile function, myocardial enzyme leakage in the coronary effluent, and
      myocardial water content were determined. The myocardial ultrastructure was also
      observed. We found that: (1) Diazoxide treatment improved the recovery of left
      ventricular developed pressure and +/-dp/dt(max) dose-dependently. Left
      ventricular end-diastolic pressure was significantly lower in diazoxide-treated
      hearts than that of hearts in Celsior solution after hypothermic preservation for
      10 h. (2) Diazoxide at 30 and 45 micromol/L significantly decreased the water
      content of myocardium and increased coronary flow of the hearts compared to those
      in control. (3) The leakage of myocardial enzymes (lactate dehydrogenase,
      creatine kinase and glutamate-oxaloacetate transaminase) in the coronary effluent
      was significantly reduced in diazoxide-treated hearts. (4) Impairment of
      myocardial ultrastructure after 10 h hypothermic preservation was alleviated in
      hearts treated with 30 micromol/L diazoxide. (5) The cardiac effects of 30
      micromol/L diazoxide were attenuated by a mitoK(ATP) blocker 5-hydroxydecanoate
      (5-HD, 100 micromol/L). These results indicate that diazoxide as a
      supplementation in cardioplegia solution could enhance myocardial protection
      during long-term hypothermic heart preservation via opening of mitochondrial
      K(ATP) channel.

PMID- 15497047
TI  - [The locus coeruleus modulates the inspiratory inhibition induced by electrical
      stimulation of the Botzinger complex].
AB  - Experiments were done on urethane anesthetized adult rabbits. Long-train
      electrical stimulation was delivered to the Botzinger complex (Bot.C) to observe
      the changes in the peak amplitude of integrated phrenic nerve activity. Then, a
      long-train electrical stimulation was delivered to the locus coeruleus (LC) or
      monosodium glutamate was microinjected into the LC . Within a certain period of
      time, another long-train electrical stimulation was delivered to the Bot.C to
      observe the responses of phrenic nerve activity. We investigated whether the LC
      could modulate the inspiratory inhibition induced by electrical stimulation of
      the Bot.C. The results are as follows: (1) Within a certain period of time after
      a long-train electrical stimulation applied at the LC, the inspiratory inhibition
      produced by electrical stimulation at the Bot.C was significantly attenuated.
      Comparing with the control stimulation that was only delivered at Bot.C without
      pre-stimulation of the LC, the inspiratory inhibition was decreased by (28.78+/
      19.49)%. (2) Similarly, after chemical stimulation of the LC with microinjection
      of monosodium glutamate, the inspiratory inhibition produced by electrical
      stimulation of Bot.C was also significantly attenuated [decreased by (19.18+/
      8.06)%]. The results obtained suggest that the LC plays a role in the modulation
      of the inspiratory inhibition of Bot.C stimulation.

PMID- 15497048
TI  - Stimulatory effects of gonadotropin-releasing hormone and dopamine on growth
      hormone release and growth hormone mRNA expression in Epinephelus coioides.
AB  - Gonadotropin-releasing hormone (GnRH) and dopamine (DA) can stimulate growth
      hormone (GH) release, but their effects on GH mRNA synthesis are controversial
      and deficient in fish. Orange-spotted grouper (Epinephelus coioides) is a
      hermaphroditic marine fish with sex reversal. Few data are available concerning
      the regulation of GH in grouper. In the present study, the effects of GnRH and DA
      on GH release and GH mRNA expression were determined using pituitary fragments of
      orange-spotted grouper under static culture conditions. After incubation from 1 h
      to 24 h, salmon GnRH (sGnRH, 100 nmol/L) stimulated the release of GH and
      increased the level of GH mRNA time-dependently. The minimum duration of sGnRH
      effect was 1 h. Both of sGnRH and mammalian GnRH (mGnRH) augmented the release of
      GH and the level of GH mRNA in a dose-dependent manner. The potency of sGnRH on
      both GH release and GH mRNA level was more pronounced than that of mGnRH. The
      effects of 1 micromol/L APO (Apomorphine), an agonist of D(1)/ D(2) dopamine
      receptors, significantly stimulated GH release and GH mRNA synthesis after
      incubation for 12 h. APO stimulated GH release and GH mRNA abundance in a dose
      dependent manner. These results demonstrate that both GnRH and DA directly
      stimulate GH release and GH mRNA expression at the pituitary level, the actions
      of GnRH are more potent than that of DA in orange-spotted grouper.

PMID- 15497049
TI  - [Isolation and electrophysiological characteristics of embryonic cardiomyocytes
      in mice].
AB  - To explore the electrophysiological characteristics of embryonic cardiomyocytes,
      single embryonic cardiomyocytes were obtained from mice at different periods by a
      collegenase B digestion approach, whole cell patch clamp recording technique was
      used to record I(f) and I(Ca-L), and spontaneous action potential was also
      recorded. The morphological and spontaneous contractile properties of the
      isolated cells appeared to be typical embryonic cardiomyocytes when the cells
      were assessed by phase-contrast microscope. Whole cell recording of isolated
      cells is easily performed by the whole cell patch clamp technique.
      Elelctrophysiological properties of I(f) and I(Ca-L) from embryonic
      cardiomyocytes have been proved to be similar to those from adult pacemaker cells
      or cardiomyocytes. The established method of isolation is simple, stable,
      effective and reliable. It allows to obtain as early as 8.5-day embryonic
      myocytes. The electrophysiological recording of embryonic cardiomyocytes will
      provide a useful model for exploring the electrophysiological characteristics of
      embryonic cardiomyocytes and the possible mechanism underlying some heart
      diseases.

PMID- 15497050
TI  - [Isolation of cardiomyocytes from the adult mouse heart].
AB  - In order to culture cardiomyocytes or to observe the contractile function of
      adult mouse cardiomyocytes, it is necessary to isolate high-yield and high
      quality cardiomyocytes at first. The mouse was injected with heparin (5,000
      IU/kg, i.p.) 20 min prior to the experimental protocol, then was sacrificed by
      cervical dislocation. The heart was excised and the aorta was cannulated rapidly.
      The cannulated heart was mounted on a Langendorff perfusion apparatus with
      constant flow and perfusion pressure was monitored. The initial perfusion
      pressure was maintained at 40 mmHg by regulating the flow rate. The heart was
      digested by 0.05 % crude collagenase I at 37 degrees C and the enzymatic
      digestion was terminated immediately when the perfusion pressure was lowered to
      28 mmHg. The heart was then cut off the cannula and the atria and aorta dissected
      away. The ventricular tissue was chopped and the single myocyte was dispersed
      gently by a wide tipped pipette. The viability of freshly isolated cardiomyocytes
      was more than 70 %. The cardiomyocytes were kept in Joklik's minimum essential
      medium containing 1 % BSA and 10 mmol/L BDM, then extracellular calcium was
      restored step-wise to a final concentration of 1.25 mmol/L. The viability of
      cardiomyocytes reduced to (40-50) % after 4 h standing. More than 90 % of rod
      shaped cardiomyocytes were quiescent and had visible cross striations and sharp
      edges. The amplitude of unloaded shortening in cardiomyocytes was (9.72+/-0.43) %
      during 1.0 Hz stimulation, (11.28+/-0.43) % at 2.0 Hz and (11.40+/-0.45) % at 5.0
      Hz. These results indicate that high yield and high quality cardiomyocytes can be
      obtained. In addition, the standards of identifying cardiomyocyte quality are
      concise and are suitable to culture the cardiomyocytes or to study the
      physiological function of cardiomyocytes.

PMID- 15497051
TI  - Sexual addiction, sexual compulsivity, sexual impulsivity, or what? Toward a
      theoretical model.
AB  - We critically review the concepts of sexual addiction, sexual compulsivity, and
      sexual impulsivity and discuss their theoretical bases. A sample of 31 self
      defined sex addicts were assessed by means of interview and questionnaires and
      compared with a large age-matched control group. A tendency to experience
      increased sexual interest in states of depression or anxiety was strongly
      characteristic of the sex addict group. Dissociative experiences were described
      by 45% of sex addicts and may have some explanatory relevance. Obsessive
      compulsive mechanisms may be relevant in some cases, and the addiction concept
      may prove to be relevant with further research. Overall, results suggested that
      out of control sexual behavior results from a variety of mechanisms. We propose
      an alternative theoretical approach to investigating these mechanisms based on
      the dual control model and recent research on the relation between mood and
      sexuality.

PMID- 15497052
TI  - The relationship between indicators of sexual compulsivity and high risk sexual
      practices among men and women receiving services from a sexually transmitted
      infection clinic.
AB  - Sexual compulsivity, defined by sexual preoccupation and lack of sexual impulse
      control, is related to high-risk sexual behaviors. However, little is known about
      the prevalence and predictors of sexual compulsivity in people at high risk for
      contracting sexually transmitted infections (STIs). In the current study,
      patients receiving diagnostic and treatment services (85% African American) at an
      urban STI clinic completed measures of demographic characteristics, sexual
      compulsivity, substance use, and sexual behaviors. Measures were administered to
      492 men and 193 women using confidential procedures and audio computer-assisted
      interviewing technology. Results showed that men and women receiving STI clinic
      services frequently endorsed multiple indicators of sexual compulsivity. In this
      mostly African American sample, individuals with scores above the 80th percentile
      on the sexual compulsivity scale (translating to over one standard deviation
      above the mean) had more sex partners, engaged in higher rates of sexual risk
      behaviors with casual or one-time sex partners, and were nearly four times as
      likely to have been recently diagnosed with multiple STIs than were individuals
      who scored below the 80th percentile. Although sexual compulsivity scores were
      associated with alcohol and other drug use, associations between sexual
      compulsivity and sexual risks were not accounted for by substance abuse. Findings
      suggest an urgent need for interventions to help men and women with sexual
      preoccupations and poor sexual impulse control to reduce their risks for sexually
      transmitted infections.

PMID- 15497053
TI  - Sexual behavior and responsiveness to sexual stimuli following laboratory-induced
      sexual arousal.
AB  - Sexual excitement can be seen as an action disposition. In this study sexual
      arousal was expected to generate sexual action and to increase interest and
      responsiveness to sexual stimuli. In two experiments, male and female
      participants were exposed to a neutral or a sexual film. We measured genital and
      subjective responses to the film, and sexual behavior following the laboratory
      visit. In Experiment 2, film exposure was followed by a task in which
      participants rated the sexual arousability of neutral and sexual pictures. Rating
      time of the sexual pictures served as an index for sexual interest.
      Responsiveness to the sexual pictures was measured by modulation of spinal
      tendinous (T) reflexes. Sexual activity, but not sexual desire, was higher for
      participants in the sexual film condition than for participants in the neutral
      condition. Sexual interest and responsiveness to still pictures were not higher
      for participants in the sexual film condition than for those in the neutral film
      condition. In addition, men who saw the neutral film showed a greater
      responsiveness to still pictures than men who saw the sexual film. The results
      support the view of sexual arousal as an emotional state generating action
      tendencies and actual sexual behavior.

PMID- 15497054
TI  - Correlates of negative attitudes toward gay men: sexism, male role norms, and
      male sexuality.
AB  - Research has shown that heterosexual men are more negative toward gay men than
      women are on measures of attitudes toward homosexual behaviour and homosexual
      persons (Kite & Whitley, 1996). Gender differences in attitudes toward gay men's
      civil rights are less clear. No empirical studies, however, have investigated
      these findings with a scale that measures specifically these three attitudinal
      subcomponents. This study was a preliminary test of a scale that measured these
      subcomponents. In addition, this study investigated the relationship between
      these subcomponents and other attitudinal measures: hostile sexism, male
      toughness, and attitudes toward male sexuality. Results revealed that attitudes
      toward homosexual behaviour and homosexual persons comprised one factor:
      affective reactions toward gay men. Results showed that men were more negative on
      affective reactions than women were. No gender differences were revealed on
      attitudes toward civil rights. I found significant correlations between affective
      reactions, hostile sexism, male toughness, and male sexuality. I discuss these
      findings in relation to traditional gender role beliefs and make suggestions for
      future research.

PMID- 15497055
TI  - Evaluation of two school-based HIV prevention interventions in the border city of
      Tijuana, Mexico.
AB  - This research project examined the individual and combined effectiveness of an
      HIV prevention workshop and a free condom distribution program in four high
      schools in Tijuana, Mexico. Adolescents (N = 320) completed baseline measures on
      sexual practices and theoretical correlates and participated in a two-part study.
      In Study 1, students were randomly assigned to an HIV prevention workshop or a
      control condition, with a 3-month follow-up assessment. Results indicate three
      significant workshop benefits regarding HIV transmission by altering sexual
      initiation, access to condoms, and traditional beliefs regarding condoms. In
      Study 2, we set up a condom distribution program at two of the participating
      schools, and students completed a 6-month follow-up assessment. Results indicate
      that exposure to the workshop followed by access to the condom distribution
      program yielded two beneficial results for reducing HIV transmission: moderating
      sexual initiation and increasing condom acquisition. Access to the condom
      distribution program alone had no effects on behavioral and psychosocial
      correlates of HIV transmission. We discuss implications of these results.

PMID- 15497056
TI  - Asexuality: prevalence and associated factors in a national probability sample.
AB  - I used data from a national probability sample (N > 18,000) of British residents
      to investigate asexuality, defined as having no sexual attraction to a partner of
      either sex. Approximately 1% (n = 195) of the sample indicated they were asexual.
      A number of factors were related to asexuality, including gender (i.e., more
      women than men), short stature, low education, low socioeconomic status, and poor
      health. Asexual women also had a later onset of menarche relative to sexual
      women. The results suggest that a number of pathways, both biological and
      psychosocial, contribute to the development of asexuality.

PMID- 15497057
TI  - Power, desire, and pleasure in sexual fantasies.
AB  - One hundred and sixty-two participants (ages 21-45) wrote open-ended sexual
      fantasies and completed self-report measures of rape myth acceptance, adversarial
      sexual beliefs, and attitudes toward women. We coded fantasies using a newly
      developed scoring system that includes themes of dominance, submission, sexual
      pleasure, and sexual desire. Men fantasized about dominance more than women did;
      they also tended to focus more on the desire and pleasure of their partner.
      Desire and pleasure were more closely linked in the fantasies of men than in the
      fantasies of women, for whom the two were distinct constructs. Although fantasies
      of submission were not associated with problematic attitudes for either gender,
      men's fantasies of dominance were associated with greater acceptance of rape
      myths. For women, greater rape myth acceptance was associated with emotional and
      romantic fantasy themes.

PMID- 15497058
TI  - Actual and desired duration of foreplay and intercourse: discordance and
      misperceptions within heterosexual couples.
AB  - One hundred and fifty-two heterosexual couples reported their actual and ideal
      duration of foreplay and intercourse, as well as their perceptions of their
      partners' desired duration of foreplay and intercourse. Further, participants
      reported the duration of foreplay and intercourse that they felt most men and
      most women wanted. Ideal length of foreplay did not differ for men and women.
      However, men reported a significantly longer ideal duration of intercourse than
      did their partners. The ideal duration of foreplay and intercourse were
      significantly longer than the actual duration for both genders. The women, but
      not the men, significantly underestimated their partners' desired duration of
      foreplay and intercourse. Further, both genders exhibited faulty stereotypes
      concerning men's but not women's ideal scripts. Men were seen as desiring a
      significantly shorter duration of foreplay and intercourse than the ideal
      reported by the men in the study. Both men's and women's perceptions of their
      partners' ideal duration of foreplay and intercourse were found to be more
      strongly related to their own sexual stereotypes than to their partners' self
      reported sexual desires, suggesting that people rely on sexual stereotypes when
      estimating their partners' ideal sexual scripts. Men's and women's ideal scripts
      and men's and women's sexual stereotypes concerning the opposite gender's ideal
      duration of foreplay were found to uniquely predict the foreplay performance
      script. For intercourse, men's and women's ideal scripts and men's stereotypes
      concerning the duration of intercourse that women want uniquely predicated the
      performance script. We present potential reasons for the discrepancy in
      individuals' performance and ideal scripts.

PMID- 15497059
TI  - Definitive treatment of traumatic biliary injuries.
AB  - BACKGROUND: We presented our experience with definitive treatment of traumatic
      biliary injuries. METHODS: Six male patients (mean age 13 years; range 2 to 32
      years) who were referred to our unit for definitive treatment of traumatic
      biliary injuries were retrospectively evaluated. Data were analyzed in terms of
      demographic characteristics, mechanisms of injuries, associated injuries,
      previous treatments, symptoms on admission, treatment at our unit, and the
      results of treatment. Outcome was assessed using modified Schweiser and Blumgart
      criteria. RESULTS: The injuries were due to blunt abdominal trauma in all the
      patients but one who had a gunshot wound. In three patients, biliary injuries
      were missed at the initial operation. On admission, three patients had external
      biliary fistulas, two had biliary strictures. One patient was sent following
      inadvertent ligation of the hepatoduodenal ligament during attempts to control
      hemorrhage. Roux-en-Y hepaticojejunostomy was performed in three patients.
      Percutaneous biloma drainage was performed in two patients, resulting in fistula
      closure in 13 and 40 days, respectively. One patient was treated by endoscopic
      retrograde cholangiopancreatography and papillotomy, which enabled fistula
      closure in three days. One patient was lost to follow-up. One patient died from
      hepatic failure 11 years after the trauma. At the end of a mean follow-up of 49
      months (range 15 to 75 months), three patients were in excellent condition, while
      one patient experienced occasional attacks of cholangitis. CONCLUSION: In
      patients with undetected biliary injuries and in those with unsuccessful repair
      attempts, biliary reconstruction should be performed in experienced
      hepatopancreatobiliary surgery units.

PMID- 15497060
TI  - [Evaluation criteria for selecting patients for surgical or nonoperative
      treatment in nonvariceal upper gastrointestinal bleeding].
AB  - BACKGROUND: We evaluated the patients who underwent surgical or nonoperative
      treatment for acute nonvariceal upper gastrointestinal bleeding. METHODS: The
      study included 31 patients (21 males, 10 females; mean age 60 years; range 19 to
      82 years) with nonvariceal upper gastrointestinal bleeding. Surgical treatment
      was performed in 14 patients (10 males, 4 females; mean age 64 years), while 17
      patients (11 males, 6 females; mean age 55.6 years) were treated conservatively.
      The two groups were compared with respect to age, sex, associated diseases,
      arterial blood pressure, pulse rate, and hematocrit values on admission, number
      of blood transfusions, endoscopic findings, cause of bleeding, and mortality.
      RESULTS: Upon admission, all the patients underwent endoscopic examination except
      for five surgically-treated patients. Peptic ulcer was detected in 74.1% of the
      bleedings. The incidences of duodenal ulcer and stomach ulcer did not differ
      between the two groups. No significant differences were found with respect to the
      causes of bleedings. The mean number of blood transfusions was 4.36 units
      preoperatively, and 2.29 units in those treated conservatively (p=0.013). The
      mean systolic (p=0.002) and diastolic pressures (p=0.029), pulse rates (p=0.003),
      and hematocrit values (p=0.011) obtained on admission differed significantly.
      Mortality occurred in only one patient (7.1%) due to cardiac failure in the
      postoperative period. CONCLUSION: Our study yielded elucidative data on the
      referral of patients to surgical treatment for nonvariceal upper gastrointestinal
      bleeding.

PMID- 15497061
TI  - [Combination of direct and indirect reduction techniques in periarticular complex
      knee fractures].
AB  - BACKGROUND: We evaluated the efficiency of treatment of comminuted intraarticular
      fractures of the knee, involving direct reduction and rigid fixation for
      articular components, and indirect reduction and biological fixation for
      metaphyseal-diaphyseal components. METHODS: Twelve patients (9 males, 3 females;
      mean age 46 years; range 22 to 71 years) with distal femoral (n=6) and proximal
      tibial (n=6) intraarticular fractures were included. There were seven closed and
      five open fractures. Intraarticular fractures were fixed directly through a
      lateral parapatellar incision; while comminuted metaphyseal-diaphyseal fractures
      were indirectly reduced and internally fixed with biological fixation methods.
      The patients were evaluated clinically and radiographically. Intraarticular bone
      and soft tissue changes were evaluated by conventional and three-dimensional
      computed tomography. The results were assessed according to the HSS (Hospital for
      Special Surgery) criteria. The mean follow-up was 43 months (range 15 to 78
      months). RESULTS: All fractures healed without any refractures, implant failures,
      or infections. The mean time to full weight-bearing was 25.5 weeks for tibial,
      and 24 weeks for femoral fractures. Leg length discrepancy occurred in all the
      patients with femoral fractures (1-2 cm), and in two patients with tibial
      fractures (1 cm). One patient with a femoral fracture had a valgus deformity of
      10 degrees. According to the HSS criteria, the results were good in five cases,
      and moderate in one case for tibial fractures; good in one case, moderate in four
      cases, and poor in one case for femoral fractures. Tomographic evaluations showed
      articular congruity in all the cases without any signs of loose bodies.
      CONCLUSION: Combination of indirect and direct reduction techniques is an
      effective method for the treatment of comminuted intraarticular knee fractures.

PMID- 15497062
TI  - Knee dislocations: an evaluation of surgical and conservative treatment.
AB  - BACKGROUND: We evaluated the results of surgical or non-operative treatment of
      knee dislocations and the effect of associated soft tissue injuries on the
      planning of treatment. METHODS: The study included 12 patients (10 males, 2
      females; mean age 34 years; range 17 to 75 years). Knee dislocations were caused
      by low-energy injuries in five patients, and by high-energy injuries in seven
      patients. All the knees were dislocated posteriorly. Three dislocations were
      open. Three patients had popliteal artery injuries and three patients had
      peroneal nerve injuries. Dislocations affecting the anterior and/or posterior
      cruciate ligaments were treated surgically (n=6), whereas the medial collateral
      ligament and lateral ligament injuries were treated non-operatively (n=6). The
      Lysholm scores and the range of motion of the knees were compared between
      surgically and conservatively treated groups. The mean follow-up period was 46
      months (range 26 to 82 months). RESULTS: The mean range of motion of the knees
      (116 degrees versus 72 degrees ; p<0.01) and the mean Lysholm scores (84.6 versus
      74; p<0.01) differed significantly between patients undergoing surgical and non
      operative treatment. Chronic laxity occurred in two knees (one with surgical, one
      with conservative treatment). Arthrofibrosis developed in four patients (one with
      surgical, three with conservative treatment). There were no deep infections.
      Superficial infections occurred in two open dislocations. CONCLUSION: Knee
      dislocations should be regarded as significant limb-threatening injuries.
      Evaluation and immediate treatment of vascular insufficiency is of primary
      importance. Then, treatment depending on the presence and severity of ligamentous
      injuries is essential to provide a stable and functional extremity.

PMID- 15497063
TI  - [Surgical treatment of type III acromioclavicular joint dislocations by a
      modified Bosworth technique].
AB  - BACKGROUND: We evaluated the results of surgical treatment of type III
      acromioclavicular joint dislocations by a modified Bosworth technique. METHODS:
      Thirty-four patients (9 females, 25 males; mean age 35 years; range 20 to 53
      years) were treated with a modified Bosworth technique for type III
      acromioclavicular joint dislocations. Dislocations were caused by falls (n=18),
      traffic accidents (n=8), and during contact sports (n=8). Involvement was on the
      right side in 23 patients, and on the left side in 11 patients. The mean time to
      operation was two days (range 1 to 4 days). Functional evaluations were made with
      the use of the Constant scores. The mean follow-up was 35 months (range 12 to 57
      months). RESULTS: The mean postoperative Constant score was 93 (range 46 to 96).
      No complications were seen during operation. The results were excellent in 24
      patients (70.6%), good in seven patients (20.6%), and poor in three patients
      (8.8%). None of the patients had to change their jobs or give up any previous
      sports activities. Radiographically, the distal clavicle appeared normal in 32
      patients, atrophied in one patient, and enlarged in another. Functional results
      were good in 12 patients (35.3%) in whom calcifications were detected in the
      coracoclavicular ligament. Dislocations recurred in three patients (8.8%). Two
      patients developed superficial infections. CONCLUSION: Surgical treatment of
      acromioclavicular joint dislocations by the modified Bosworth technique is a
      convenient option with regard to short- and long-term results.

PMID- 15497064
TI  - An evaluation of the underlying causes of fall-induced hip fractures in elderly
      persons.
AB  - BACKGROUND: Falls are the major cause of hip fractures in elderly patients. The
      aim of this prospective study was to investigate the underlying causes of fall
      induced hip fractures in the elderly. METHODS: The study included 32 patients (18
      males, 14 females; mean age 78 years; range 57 to 95 years) who had proximal
      femoral fractures following an unexpected and sudden fall from about a meter
      height at a moment of lying, sitting, or standing position. Underlying causes of
      falls were sought, including previous falls, stroke, polyneuropathy, motion
      disorders, dementia, vision problems, fainting, vestibular pathologies, and
      cardiac diseases. RESULTS: Eight patients (25%) had a history of previous falls
      and 12 patients (37.5%) had a history of stroke. Polyneuropathy, Parkinson's
      Disease, and dementia were diagnosed in eight (25%), three (9.4%), and five
      (15.6%) patients, respectively. Twenty-one patients (65.6%) had neurologic
      diseases, 11 patients (34.4%) had cataract or other vision problems, eight
      patients (25%) had osteoarthritis and rheumatoid arthritis, 10 patients (31.3%)
      had vestibular pathologies, and 17 patients (53.1%) had cardiac diseases such as
      heart failure, orthostatic hypotension, ischemic heart disease, and arrhythmia.
      CONCLUSION: In order to prevent recurrent falls, risk factors associated with
      falls should be determined and preventive treatment and measures should be put
      into practice in elderly patients who have fall-induced injuries.

PMID- 15497065
TI  - [Rectal foreign bodies: a report of four cases].
AB  - Foreign bodies were detected in the rectum in four male patients with ages
      ranging from 36 to 64 years. The materials were an iron rod, a specially shaped
      wooden device, and in two cases, deodorant caps. They were extracted with the
      patients in lithotomy position after anal dilatation, under general anesthesia in
      three cases, and spinal anesthesia in one case. No procedure-related
      complications occurred and the patients were discharged 24 hours after the
      operation.

PMID- 15497066
TI  - [A case of posttraumatic intracranial meningioma].
AB  - Several etiologic factors have been proposed in the development of meningiomas,
      including trauma, radiation, oncogenic viruses, chromosomal abnormalities, and
      hormonal factors. We presented a 71-year-old female patient who had undergone an
      operation for a head trauma 27 years ago. Brain computed tomography scans showed
      a contrast-enhancing intracranial mass lesion, 5 x 4 x 4 cm in size, leading to
      diffuse edema in the left frontal region. At surgery, a tumoral mass was detected
      below the former craniotomy flap, with dural invasion, and a total excision was
      performed. Two silver clips were also noted in the previous surgical site.
      Histopathologic diagnosis was made as a transitional meningioma. No recurrences
      were detected within a year follow-up period.

PMID- 15497067
TI  - [A case of Rapunzel syndrome].
AB  - Trichobezoars are concretions of hair casts in the stomach associated with
      trichotillomania and trichophagia. The condition is termed Rapunzel syndrome when
      formation of a huge trichobezoar extends to the small bowel, resulting in
      gastrointestinal obstruction. We present a 19-year-old girl who had complaints of
      colicky abdominal pain, nausea and vomiting seven years after surgical treatment
      for a gastric trichobezoar. Gastric endoscopy was performed with an initial
      diagnosis of recurrent trichobezoar, which revealed a huge one. The patient
      underwent laparotomy, during which a huge trichobezoar with a long tail was
      totally removed by an anterior gastrotomy. Following removal of the lesion, the
      antrum was observed with multiple ulcers secondary to extensive pressure.
      Postoperative period was uneventful. A subsequent psychiatric consultation
      revealed depressive personality disorder.

PMID- 15497068
TI  - [A case of superior mesenteric artery syndrome following head trauma].
AB  - A twenty-four-year-old male patient developed a high level gastrointestinal
      obstruction during hospitalization in intensive care unit following a head
      trauma. He suffered from vomiting and weight loss and was unable to tolerate
      nasoenteral feeding. Barium radiographs revealed obstruction in the third portion
      of the duodenum. Upon failure of conservative treatment, laparotomy was
      performed, which showed compression and obstruction of the third portion of the
      duodenum by the superior mesenteric artery. A side-to-side duodenojejunostomy
      performed yielded complete relief of compression symptoms. The patient was
      symptomless in the sixth postoperative year. Although primary treatment of
      superior mesenteric artery syndrome is conservative, surgical treatment should be
      considered in unresponsive patients.

PMID- 15497069
TI  - [A second-degree burn related to air bag deployment: a case report].
AB  - Although air bags have been shown to reduce mortality and morbidity in motor
      vehicle crashes, they are associated with specific injuries. Burns due to air bag
      deployment account for more than 5% of all air bag injuries and typically involve
      upper extremities or head and neck. Aside from friction burns, thermal and
      chemical burns are also seen resulting from the use of certain chemicals for the
      deployment mechanism. We reported a female patient who presented to the emergency
      department with a second-degree burn in her left breast, six days after a motor
      vehicle crash. She was treated with irrigation with saline solution and 2% sodium
      fusidate ointment. The burn area healed within a week, without any further
      treatment. Only a slight scar tissue remained after a six-month follow-up.

PMID- 15497070
TI  - [The hospital in the midst of changing -- the department of radiology in the
      course of transition to a radiology service center].

PMID- 15497071
TI  - Experimental autoimmune encephalomyelitis (EAE): lesion visualization on a 3
      Tesla clinical whole-body system after intraperitoneal contrast injection.
AB  - PURPOSE: To investigate the intravital visibility of CNS lesions in rats with
      experimental autoimmune encephalomyelitis (EAE), the animal correlate of multiple
      sclerosis, using a 3-Tesla (T) whole-body MR system. MATERIALS AND METHODS: Three
      healthy Dark Agouti (DA) rats and 16 DA rats with clinical signs of EAE were
      examined on a 3T whole body-system using a normal wrist coil. In total, 25
      examinations were preformed using T2- and T1-weigthed images in transverse and
      sagittal orientation with a slice thickness of 2 mm or 1 mm (voxel size up to 0.2
      x 0.2 x 1 mm). Sedation was achieved by intraperitoneal injection of ketamine and
      xylazine. In addition, T1-weighted images were obtained after the instillation of
      1.0 ml of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) (0.5 mmol/ml)
      into the peritoneal cavity. RESULTS: T2- and T1-weighted images of the brain and
      spinal cord with high spatial and contrast resolution could be obtained in all
      animals. The anatomical details of the olfactory bulb glomeruli, cerebellum
      foliae, ventricles and corpus callosum were clearly visible. The EAE lesions
      presented as hyperintense areas in T2-weighted images and could be demonstrated
      in all clinically affected animals by MRI and histologically verified. In total,
      the 16 affected rats had 28 cerebral and 2 spinal cord lesions (range 1 to 4,
      median 2). Contrast enhancement was noted in 12 animals and ranked as severe in
      ten and moderate in two cases. No adverse effects were noted due to sedation or
      intraperitoneal contrast injection. CONCLUSIONS: The intravital demonstration of
      cerebral and spinal cord EAE lesions in rats is possible on a 3T whole-body MR
      scanner using a normal wrist coil. Intraperitoneal injection of ketamine/xylazine
      and contrast agent is an easy, safe and effective procedure in rats.

PMID- 15497072
TI  - Clinical and angiographic outcome after interventional treatment of the iliac
      arteries with a new carbofilm coated stent: preliminary results.
AB  - PURPOSE: To evaluate the handling, the procedural success rate and the six-month
      outcome of a new Carbofilm coated balloon-expandable stent in iliac artery
      lesions. MATERIALS AND METHODS: In a prospective study, 46 stenoses and 2
      occlusions of the iliac arteries were primarily stented in 30 patients with the
      Isthmus CarboStent (Sorin Biomedica Cardio S.p. A., Saluggia, Italy). The ankle
      brachial index (ABI) at rest was determined before intervention and at the six
      month follow-up visit. Iliac angiography, including intraarterial pressure
      measurement, was performed before intervention, post-procedurally and at the
      follow-up visit. RESULTS: All lesions were treated with procedural success. The
      mean degree of all stenoses was 73.9 % +/- 14.6 before and 2.4 % +/- 8.2 after
      intervention. The mean pressure gradient was 15.6 mm Hg +/- 10.1 before and 2.5
      mm Hg +/- 2.7 after treatment. No or only a mild restenosis developed in 27
      patients. The mean ABI increased from 0.64 +/- 0.21 to 0.86 +/- 0.33 and the mean
      pressure gradient was 2.7 mm Hg +/- 5.4 at the six-month visit. The six-month
      patency rate was 97.9 %. Three patients showed acute stent thrombosis due to an
      insufficient postprocedural antiplatelet regimen. DISCUSSION: The Isthmus
      CarboStent is a safe and easy to handle balloon-expandable stent for
      interventional therapy of iliac artery lesions. The six-month patency rate is
      good. Despite its Carbofilm coating, postprocedural antiplatelet therapy is
      necessary.

PMID- 15497073
TI  - Evaluation of balanced steady-state free precession (TrueFISP) and K-space
      segmented gradient echo sequences for 3D coronary MR angiography with navigator
      gating at 3 Tesla.
AB  - PURPOSE: To test the feasibility of k-space segmented gradient-echo pulse
      sequences for free-breathing coronary magnetic resonance angiography (cMRA) on a
      clinical 3T system. MATERIALS AND METHODS: T2-prepared, fat-suppressed turbo
      field echo (TFE, turboFLASH, SFPGR) as well as balanced TFE (b-TFE, trueFISP,
      FIESTA, segmented SSFP) sequences with navigator gating for prospective motion
      correction were applied on a 3T system equipped with a six-element phased-array
      cardiac coil. In 15 healthy volunteers, the right coronary artery (RCA) was
      examined with TFE and b-TFE sequences. Due to examination time limitations, the
      left coronary artery (LM/LAD) was examined exclusively with the TFE sequence in
      ten volunteers. Image quality was graded on a five point scale (0 = not
      visualized to 4 = excellent). The length, diameter and sharpness of the vessels
      and the contrast-to-noise ratios (CNR) were measured. RESULTS: 98 % of all major
      segments (proximal/middle/distal) of the RCA could be seen with the TFE sequence
      and 82 % with the b-TFE sequence. The image quality for the three segments was
      graded higher for the TFE sequence (2.7/2.7/1.5) than for the b-TFE sequence
      (1.9/1.6/0.9) with P: (< or = 0.001/< or = 0.004/< or = 0.056). The kappa of the
      interobserver variability was 0.75 for the TFE sequence and 0.8 for the b-TFE
      sequence. The measured vessel lengths were longer for the TFE sequence (95 +/- 22
      mm) than for the b-TFE sequence (80 +/- 40 mm; P < or = 0.115). No significant
      changes (P < or = 0.074, P < or = 0.145) in diameter and vessel sharpness of the
      RCAs were observed between the TFE (2.4 +/- 0.3 mm, 60 % +/- 5) and b-TFE
      sequences (2.4 +/- 0.3 mm, 62 % +/- 6). The CNR was higher for the TFE sequence
      (10.1 +/- 3.4) than for the b-TFE sequence (6.6 +/- 2.1; P < or = 0.014). All ten
      main and proximal segments of the LM/LAD, which were examined exclusively with
      the TFE sequence, were visible with grade 2.5 and 2.1. The middle segment was
      visible in seven cases with grade 1.3. In three cases, the distal segment was
      visible with grade 0.5. The vessel length was 78 +/- 27 mm and the CNR 11.9 +/-
      2.4. CONCLUSION: The conventional TFE technique has demonstrated good feasibility
      for cMRA at 3T. In its operational availability at 3T, the b-TFE sequence is
      inferior to the TFE sequence.

PMID- 15497074
TI  - [Value of electron beam tomography (EBT)].
AB  - Electron beam tomography (EBT) has been scientifically evaluated to a much lesser
      degree for non-cardiac indications than for cardiac purposes. Therefore, four
      groups of investigators in Berlin (2), Mannheim and Munchen, which were supported
      by the Deutsche Forschungsgemeinschaft (DFG), included applications outside the
      heart in their evaluation of EBT technology. EBT has proven useful to look for
      pulmonary embolism and to assess other vessels (aorta, aortic branches, and
      intracranial arteries). Imaging of the lung parenchyma benefits from its
      intrinsic high contrast and from the fast data acquisition of EBT. Limited photon
      efficiency, higher radiation exposure, increased noise levels and other
      artifacts, however, markedly reduce the value of EBT for imaging of low contrast
      objects compared to conventional spiral CT and multislice CT (MSCT),
      compromising, in particular, the morphologic depiction of parenchymal abdominal
      organs and the brain. Consequently, scientific studies to further evaluate EBT
      for scanning of the brain and parenchymal abdominal organs were not pursued.
      Radiation exposure for non-cardiac EBT studies is up to three times higher than
      that for respective spiral CT studies, and in children EBT can only be advocated
      in select cases. Radiation exposure for the various prospectively triggered
      cardiac examination protocols of EBT is lower than that for conventional coronary
      angiography. Radiation exposure in cardiac multislice CT exceeds severalfold that
      of EBT, but the dose efficiency of EBT and MSCT are similar due to higher spatial
      resolution and less image noise of MSCT. In addition, modifications of MSCT (ECG
      pulsing) can further reduce radiation exposure to the level of EBT. Technical
      improvements of the EBT successor scanner "e-Speed" enable faster data
      acquisition at higher spatial resolution. Within comparative studies, the "e
      Speed" will have to prove its value and competitiveness, particularly in
      comparison with multislice CT. After profound scientific assessment in a
      multicenter evaluation supported by the Deutsche Forschungsgemeinschaft (DFG) and
      regardless of the specific suitability of electron beam tomography for various
      cardiac and some non-cardiac indications, the investigators unanimously find the
      electron beam tomograph Evolution C150 XP not suitable as a whole body CT
      scanner.

PMID- 15497075
TI  - [The diagnostic value of radial multiplanar reformatting (MPR) in the CT
      diagnosis of pulmonary embolism].
AB  - PURPOSE: To evaluate the diagnostic value of radial reformatting of axial
      multislice CT (MS-CT) data sets in the presumptive diagnosis of pulmonary
      embolism. MATERIALS AND METHODS: In 126 cases with the presumptive diagnosis of
      an acute pulmonary embolism, 4- and 8-slice axial MS-CT data sets were radially
      reformatted. The pulmonary vessels were evaluated by five experienced
      radiologists who determined the number of thrombi at the level of the segmental
      and subsegmental arteries. A pulmonary artery was considered as thrombosed if it
      showed at least one unambiguous filling defect on two consecutive sections. It
      was determined whether the artery was uniformly opacified without filling
      defects, contained thrombotic material or was completely occluded by a blood
      clot. Pulmonary vessels that could not be evaluated because of moving artifacts
      or inadequate opacification were classified as negative. Finally, all experts
      gave a subjective estimate concerning the simplicity of the diagnosis for both
      reconstructions. RESULTS: The diagnosis of thromboembolism at a subsegmental
      level was significantly different for axial sections and radial reconstruction:
      at 4-slice CT, 77 subsegmental thromboembolisms were found in axial sections vs.
      98.6 in radial reconstructions; at 8-slice CT, 23.6 in axial sections vs. 31.2 in
      radial reconstructions; and using the combined evaluation, 103.2 in axial
      sections vs. 130.6 in radial reconstructions, with a significance of p = 0.043.
      The five judges did not find any significant differences in the number of the
      blood clots in each pulmonary segment. Concerning the simplicity of the
      diagnosis, the subjective judgment classified the radial reconstructions as
      better in 49.7 % and the axial sections as better in 22 %. The radial
      reconstructions of the 4-slice CT were classified as better in 45.7 % vs. 25 %
      and the 8-slice CT as better in 66 % vs. 16 %. CONCLUSION: Using radial
      multiplanar reformatting of the MS-CT data sets improves significantly the
      recognition of subsegmental pulmonary embolism.

PMID- 15497076
TI  - [Value of cardiac multislice spiral CT for the assessment of degenerative aortic
      stenosis: comparison with echocardiography].
AB  - OBJECTIVE: To non-invasively assess the severity of aortic valve stenosis (AS) by
      the determination of aortic valve calcification (AVC) using multislice spiral
      computed tomography (MSCT). MATERIALS AND METHODS: Forty-one consecutive patients
      (17 male, 24 female, mean age 71.0 +/- 7.9 years) with a history of AS and an
      aortic valve area < or = 2 cm (2) underwent retrospectively ECG-gated 4-slice
      MSCT and echocardiography. The AVCs were quantitatively assessed using the score
      described by Agatston as well as by calculating the calcium mass. The
      echocardiographically determined aortic valve area (AVA) and the severity of AS
      according to the ACC/AHA guidelines were compared to the degree of aortic valve
      calcifications. Pearson's correlation coefficient, cut-off values, kappa test and
      F-test with post hoc Bonferroni t-tests were calculated. RESULTS: Calcium scores
      were significantly higher in patients with severe AS, when compared to mild or
      moderate AS (p < 0.001). In patients suffering from severe AS, the mean Agatston
      score was 4125.5 +/- 1168.9 (calcium mass 904.1 +/- 263.3) while in patients with
      moderate and mild AS the corresponding values were 1596.3 +/- 987.0 (319.1 +/-
      208.3) and 785.9 +/- 390.1 (149.1 +/- 90.2), respectively. Pearson's correlation
      coefficients were r = - 0.75 for the Agatston score and r = - 0.72 for the
      calcium mass. There was a moderate agreement between severity of AS according to
      the ACC/AHA guidelines and the degree of AS determined from AVC scores with kappa
      = 0.6091 and kappa = 0.6985, respectively. CONCLUSION: Severe AS may be
      differentiated from moderate or mild AS using cardiac MSCT. Extensive
      calcifications of the aortic valve presenting with an Agatston-Score > or = 2824
      (calcium mass > or = 611) indicate a severe AS and should be taken as an
      indication for further diagnostic workup.

PMID- 15497077
TI  - [MR-coronary angiography: comparison of SSFP and spoiled GRE sequence (bright
      blood technique) and a TSE sequence (black blood technique) in healthy
      volunteers].
AB  - PURPOSE: Comparison of a free breathing steady-state free precession (SSFP), a
      spoiled gradient-echo (GRE) and a turbo spin-echo sequence (TSE) for imaging of
      the coronary arteries (MRCA) in healthy volunteers. MATERIALS AND METHODS: Twenty
      two healthy volunteers were imaged with a standard clinical scanner (1.5 T,
      Intera, Philips), with the right coronary system imaged in 11 and the left
      coronary system in the other 11 volunteers. Images were obtained with a 3D-SSFP
      (balanced TFE, TR 6.2 ms, TE 3.1 ms, alpha 65 degrees ), a 3D-GRE (TFE, TR 7.2
      ms, TE 2.2 ms, alpha 30 degrees ) and a 2D-TSE (Dual-IR, TR 2RR, TE 25 ms)
      sequence. The in plane resolution was 0.7 x 0.8 mm for both the SSFP and GRE
      sequence with an effective slice thickness of 1.5 mm. For the TSE sequence, an in
      plane resolution of 0.7 x 0.9 mm and a slice thickness of 3.0 mm were used. All
      investigations were performed using prospective navigator gating and slice
      following technique. The signal-to-noise ratio (SNR) and contrast-to-noise ratio
      (CNR) for the blood pool to myocardium and blood pool to epicardial fat were
      calculated. Image quality and measurement artifacts were assessed for all
      sequences by 5 independent investigators using a 4- and 5-point grading scale.
      RESULTS: CNR was significantly higher for the GRE sequence compared with the SSFP
      sequence and TSE sequence (mean 20.8 +/- 4.8 vs. 14.6 +/- 5.0 and 10.1 +/- 3.7
      for blood pool to myocardium; mean 27.5 +/- 6.3 vs. 16.4 +/- 5.4 and 18.1 +/- 5.7
      for blood pool to fat). The SNR revealed no significant differences between the
      SSFP and GRE sequences. The SSFP and the TSE sequences showed significantly more
      artefacts than the spoiled GRE sequence. Image quality was graded slightly higher
      for the GRE than for the SSFP sequence for the right coronary system, while there
      was no substantial difference in the left coronary system (median 2.1 +/- 0.6 and
      2.5 +/- 0.6 vs. 2.5 +/- 0.8 and 2.6 +/- 0.7 for the right and left coronary
      system). In comparison, image quality was lower with the TSE sequence (median 2.9
      +/- 0.5 for the right coronary system with p < 0.05 vs. GRE sequence and 3.0 +/-
      0.3 for the left coronary system). CONCLUSION: For the scan parameters chosen in
      this study, the GRE-sequence represents the most robust technique for imaging of
      the coronary arteries. Currently, the TSE sequence is no alternative.

PMID- 15497078
TI  - [Normal cardiac diameters in cine-MRI of the heart].
AB  - PURPOSE: To measure the normal diameters of cardiac cavities in standard cardiac
      views using cine MRI. MATERIALS AND METHODS: Fifty-six volunteers were examined
      (27 male, 29 female) on a 1.5 T MR unit with ECG-triggered single shot free
      precision (SSFP) cine MR sequences and parallel image acquisition. Standardized
      echocardiographic planes were used to depict the heart of all volunteers (short
      axis, 4-chamber view, left and right 2-chamber views). The different diameters of
      the cardiac cavities were measured using a fixed protocol. RESULTS: For the
      estimation of ventricular dilatation, the important female/male cross diameters
      of the left ventricle are 45.2 +/- 3.4/51.6 +/- 4.6 mm diastolic and 30.5 +/-
      3.5/33.8 +/- 3.6 mm systolic, and of the right ventricle 30.7 +/- 3.8/37.1 +/-
      5.9 mm diastolic and 22.3 +/- 3.8/28.1 +/- 4.4 mm systolic. For the determination
      of a left ventricular hypertrophy, relevant septal wall thickness measured in the
      short axis of the left ventricle of female/male volunteers are 8.0 +/- 1.0/9.9 +/
      1.2 mm diastolic and 10.9 +/- 1.4/13.6 +/- 1.9 mm systolic. The measured normal
      values of male volunteers were generally higher than those of female volunteers.
      The thickness of the ventricular septum correlated well when measured in the
      short axis and 4-chamber view. When measured in the 4-chamber view, the
      longitudinal diameter of the ventricles had a higher value in diastole and a
      lower value in systole, compared to the 2-chamber views of the right and left
      cardiac cavities. The atrial longitudinal diameters were higher in the 4-chamber
      view compared to the 2-chamber views, without any difference in systole or
      diastole. CONCLUSION: Diameters of cardiac cavities are easily and quickly
      measured. Using the tables with the normal values published here, it is simple to
      estimate an abnormal size of the heart.

PMID- 15497079
TI  - [Characterization of hepatic tumors with contrast-enhanced ultrasound and digital
      grey-scale analysis].
AB  - PURPOSE: The characterization of different liver tumors is of therapeutic and
      prognostic relevance and has been the purpose of several studies. Although
      ultrasound offers the opportunity to detect hepatic tumors without ionizing
      radiation, its previous techniques did not lead toward a definitive
      differentiation of different tumor entities. The purpose of this study was the
      clinical evaluation of contrast enhanced ultrasound followed by quantitative
      digital analysis in patients with focal hepatic tumors. MATERIALS AND METHODS: In
      a prospective study, 50 patients (18 females, 32 males, age 28 to 83 years, mean
      age 59.4 years) with liver tumors previously detected by CT (n = 47) or MRI (n =
      3) were examined by ultrasound of the upper abdomen using conventional technique
      and phase inversion technique after intravenous application of sulfur-based
      contrast enhancer SonoVue. At scheduled intervals after application of the
      contrast enhancer, a digital image was stored and the characteristic signal
      course of each lesion determined semiquantitatively. The gold standard was either
      resection (n = 17), percutaneous needle biopsy (n = 19) or the clinical course (n
      = 14). RESULTS: While the percentage of tumors correctly characterized by CT/MRI
      amounted to 78 %, the percentage increased from 60 % using conventional
      ultrasound to 86 % using contrast enhanced ultrasound including grey-scale
      analysis. Typical graphs were achieved for different tumor entities on digital
      grey-scale analysis. The optimal intervals for the differentiation of particular
      entities were 20 and 100 seconds after injection. CONCLUSION: Quantification of
      contrast enhanced ultrasound is an addition to the previous diagnostic procedure
      in hepatic tumors. It offers the possibility of an investigator-independent
      characterization of lesions and should be evaluated in further studies.

PMID- 15497080
TI  - [Is the renal excretion of orally applied diatrizoate (Gastrografin) a reliable
      marker of gastrointestinal perforation or dehiscence of a gastrointestinal
      anastomosis?].
AB  - PURPOSE: Renal excretion of orally or rectally applied Gastrografin is reported
      to be a reliable indicator of a perforation or a postoperative anastomotic
      dehiscence of the GI-tract. The study was conducted to determine whether
      increased attenuation of the urine measured by CT after oral or rectal
      application of Gastrografin can give reliable evidence of any leakage from the
      gastrointestinal tract. MATERIALS AND METHODS: Urine samples of 33 patients, who
      underwent a Gastrografin-enhanced fluoroscopic examination of the esophagus or
      the GI-tract for different clinical reasons, were examined by CT. The samples had
      been taken immediately before and 60 to 90 minutes after application of 100 ml
      Gastrografin. The results were compared with those of 5 healthy volunteers, who
      took urine samples before, 30, 60, 90, and 120 minutes after drinking 100 ml of
      Gastrografin. RESULTS: Maximal attenuation of the volunteers' urine samples was
      achieved 60 to 90 minutes after Gastrografin application with a mean of 50
      Hounsfield units (HU), SD = 17 HU. The urine of three patients with
      radiologically proven fistula or dehiscence of a GI-tract anastomosis had no
      relevant increase in attenuation. Three other cases without any clinical or
      radiological evidence of an anastomotic leak had a substantial increase in the
      attenuation of the urine probes (87, 110, and 290 HU, respectively). CONCLUSION:
      The CT-measured urine samples as evidence of renal excretion of orally or
      rectally applied Gastrografin are not reliable for the detection of leaks from
      the GI-tract.

PMID- 15497081
TI  - [Diagnosis and staging of pancreatic carcinoma: MRI versus multislice-CT -- a
      prospective study].
AB  - PURPOSE: To evaluate multislice-CT versus MRI in the diagnosis and staging of
      pancreatic carcinoma in a prospective multi-reader analysis. MATERIALS AND
      METHODS: Fifty patients with suspected pancreatic carcinoma underwent both
      multislice-CT (4-Row, "hydro-technique") and state-of-the-art MRI (two 1.5 T
      units). In correlation with histopathologic findings or in case of a non-lesion
      diagnosis by follow-up (6-month interval), we evaluated MRI versus CT in a multi
      reader analysis (2 reader pairs) for: 1. diagnostic quality; 2. examination time;
      3. accuracy of potential resectability; 4. kappa analysis of observer variations;
      and 5. overall diagnostic reliability. RESULTS: A total of 28 lesions (n = 22
      malignant, n = 6 benign) were present in the cohort group versus 22 patients
      without a focal lesion (n = 10 pancreatitis, n = 12 no tumor). For lesion
      detection, CT had a sensitivity of 100/89 % (reader pair 1/2) and specificity of
      77 %, and MRI had a sensitivity of 75/89 % and specificity of 77/73 %. For the
      subgroup of adenocarcinomas of the pancreas (n = 17), we found a sensitivity of
      100 % and a specificity of 61 % for CT versus a sensitivity of 82/94 % and a
      specificity of 67/61 % for MRI. The accuracy for determining the resectability
      was 91/82 % for CT and 90/82 % for MRI. The kappa analysis showed a good
      correlation for CT (0.71) and a moderate correlation of both groups for MRI
      (0.49). CONCLUSION: CT and MRI showed comparable results in the detection of
      pancreatic carcinomas as well as in the determination of resectability. Chronic
      pancreatitis as a "tumor-like-lesion" was the major factor of a missed diagnosis.
      The results of multi-reader analysis for both reading groups were almost
      identical with a moderate to good kappa correlation. There is no reason to prefer
      MRI (more expensive) over CT for patients with the presumptive diagnosis of
      pancreatic cancer.

PMID- 15497082
TI  - [CT-angiography with a 16-row CT scanner for perioperative evaluation of the
      hepatic arteries].
AB  - PURPOSE: To evaluate the efficiency of CT angiography (CTA) with 16-row MSCT
      compared with MR angiography (MRA) in analyzing the arterial anatomy in patients
      undergoing liver surgery. MATERIALS AND METHODS: In 30 patients, MRA and CTA
      studies of the abdominal vessels were reviewed. CT parameters: slice thickness 3
      mm; collimation 1.5; reconstruction interval 2 mm (Philips MX 8000 IDT); 120 ml
      contrast media (400 mg/ml) at a rate of 4 ml/sec; acquisition of arterial-phase
      scans. The anatomy of the hepatic artery was evaluated from axial and
      reconstructed maximum-intensity-projection (MIP) images ("Slab-Viewer", Philips).
      MR parameters: contrast-enhanced coronal FLASH-3D sequences; slice thickness 1.4
      mm; TR 3.47, TE 1.3; 1.5 T scanner (Siemens Somatom). Image quality was rated
      with a scoring system. Contrast enhancement of the hepatic artery and the liver
      parenchyma was measured. RESULTS: The image quality of CTA was rated as excellent
      in 18 (MRA 5); good in 8 (MRA 22); satisfactory in 4 patients (MRA 3), and non
      diagnostic in 0 patient (MRA 1). Compared to MRA, the image quality of CTA was
      better in 15/30 patients; equal for both in 13 and worse in 2 patients. CTA
      provided a better depiction of the segmental branches of the hepatic arteries in
      15/30 patients and revealed important anatomic variations of the hepatic artery
      in 8/30 patients. These variations were not be seen in MRA: e. g., MRA missed a
      left gastric arterial supply to the left liver. The ratio of contrast enhancement
      in liver parenchyma and hepatic artery was 4.7 in CTA and 4.5 in MRA. CONCLUSION:
      CTA with multislice scanners delivers better image quality and depiction of the
      hepatic arteries than MRA. Thus, MRI of the hepatic arteries can be replaced by
      routine CT, which is already part of the preoperative evaluation for liver
      transplantation.

PMID- 15497083
TI  - [Uterine adenomyosis in infertile patients: MR imaging findings and clinical
      conclusions].
AB  - PURPOSE: To evaluate the clinical value of magnetic resonance imaging (MRI) of
      the uterus and the pelvis in infertile female with symptomatic endometriosis for
      the assessment of uterine morphology and function. MATERIALS AND METHODS: Forty
      one infertile women (mean age: 33.2 years) with symptomatic endometriosis
      documented by laparoscopy were evaluated with high-field MRI (Sonata, Siemens)
      using T2- and T1-weighted sequences. In addition, the patients underwent
      hysterosalpingoscintigraphy (HSSG) for evaluation of the uterotubal transport
      capacity. Pathologic findings of the uterine junction zone were correlated with
      the laparoscopic results, clinical symptoms and uterotubal transport capacity.
      RESULTS: Adenomyosis was diagnosed on T2-weigthed MR-images in 35 (85.4 %)
      patients (focal adenomatosis in 26 patients and diffuse adenomatosis in 9).
      Patients showing signs of adenomyosis tended to be older than patients without
      adenomyosis (mean age 34.1 years vs. 30.1 years) and showed a longer history of
      symptomatic endometriosis. A positive transport capacity in HSSG was observed in
      73.1 % (19/26) of the patients with focal adenomyosis and in only 22.2 % (2/9) of
      patients with diffuse adenomyosis. In 83.3 % (5/6) of the patients without signs
      of adenomyosis, a positive uterotubal transport was documented. CONCLUSION: MRI
      of the uterus is a helpful diagnostic tool for the diagnosis of adenomyosis and
      for planning further therapies. Patients with the diagnosis of adenomyosis showed
      a reduced uterotubal transport capacity that depended on the severity of
      adenomyotic changes and might be a possible cause of infertility.

PMID- 15497084
TI  - [Uterine fibroid embolization with spheric micro-particles using flow guiding:
      safety, technical success and clinical results].
AB  - PURPOSE: To evaluate safety and mid term efficacy (> or = 1 year follow-up) of
      uterine fibroid embolization (UFE) using spherical particles (Embosphere) in a
      study applying criteria identical to those submitted to the FDA for initial
      material approval. MATERIALS AND METHODS: Twenty of the first 26 consecutive
      patients referred for potential UFE were enrolled in the study. Pre
      interventional MRI was used to assess morphologic contraindication to UFE. The
      embolization procedures were performed from a unilateral femoral approach using
      4F selective catheters in straight vessels, > 2 mm in diameter, and micro
      catheters in smaller and tortuous arteries. The endpoint of the "flow guided"
      embolization was defined by reaching the angiographic "pruned tree" appearance
      and sluggish flow in the main stem of the uterine artery. Assessment of
      morphologic mid term success was done by MRI 10 days, 3 months, 6 months, 9
      months and 1 year after UFE. The clinical mid term success was assessed by having
      questionnaires completed for menstrual bleeding, retention of clinical
      (symptomatic) benefit and quality of life. RESULTS: Technical success was 100 %,
      with 8 minor (2 post-interventional collapses, 2 hematomas, 4 relevant post
      embolizations syndromes, 1 spontaneous expulsion of a submucous myoma) and 3
      major complications (1 hysterectomy because of vaginal bleeding for 5 weeks, 1
      transient amenorrhea and 1 spontaneous expulsion of myoma with transient bleeding
      requiring admission). In 17 of 19 patients, MRI showed total fibroid
      devascularization throughout the entire follow-up. The average shrinkage of the
      dominant fibroid was 71.3 % at one year. The menstrual bleeding record in the
      cohort group fell from an average of 501.6 before treatment to 76.2 points at one
      year. At the same time, the clinical symptoms significantly improved. The patient
      satisfaction with the applied therapy was > 95 % at 1 year. One patient with
      residual fibroid perfusion underwent a second procedure, which achieved complete
      devascularization and adequate clinical success at one year. The second patient
      with incomplete devascularization had a persistent clinical benefit. CONCLUSION:
      Under controlled study conditions, flow guided UFE with spherical particles
      achieves high overall success and patient satisfaction. MRI provides exact
      morphologic description of the fibroid for the initial evaluation and for post
      procedural follow-up.

PMID- 15497085
TI  - [Percutaneous thermoablation of pulmonary metastases. Experience with the
      application of laser-induced thermotherapy (LITT) and radiofrequency ablation
      (RFA), and a literature review].
AB  - PURPOSE: Evaluation of technical aspects, local efficiency and complications of
      thermoablative procedures, such as radiofrequency ablation (RFA) and laser
      induced thermotherapy (LITT), in percutaneous lung metastases. MATERIALS AND
      METHODS: Techniques of thermal ablative procedures of RFA and LITT are presented.
      For primary positioning, monitoring and therapy control, computed tomography (CT)
      or magnetic resonance imaging (MRI) was performed. Different monopolar systems
      and one bipolar system were available for RFA and two different cooling systems
      for LITT. Percutaneous CT-guided RFA was performed on 32 metastases in 20
      patients and percutaneous LITT on 34 metastases in 24 patients. Inclusion
      criteria were metastases < or = 5 cm in diameter in unresectable patients with up
      to 3 metastases per lung. All treatments were performed on outpatient basis using
      analgosedation. RESULTS: In our patient group, all patients tolerated both the
      RFA and LITT procedures well with mild sedation. The pneumothorax rate was 15 %
      (5/32 procedures) for the RFA group and 12 % (4/34 procedures) for the LITT
      group, without insertion of a chest tube. In all RF ablations, a complete "roll
      off" (increase in impedance) was achieved. Local tumor control rate in the 6
      month follow-up was 85 % for RFA and 91 % for LITT. Nineteen of the 20 patients
      treated are still alive, one patient died from tumor progression. CONCLUSION:
      Both pulmonary RFA and LITT allow safe thermal ablation of pulmon arg metastases
      with a low complication rate and an acceptable tumor control rate.

PMID- 15497086
TI  - [Value of various MR sequences using 1.5 and 3.0 Tesla in analyzing cartilaginous
      defects of the patella in an animal model].
AB  - PURPOSE: Comparison of MRI and macropathologic evaluation using various sequences
      and field strengths in the detection, localization and measurement of cartilage
      defects in an animal model. MATERIALS AND METHODS: After open creation of
      retropatellar cartilage defects of various widths, depths and locations in 8
      cadaveric sheep knee joints, the knees were examined using a fat-suppressed (FS),
      proton density-weighted (PD) fast spin echo (FSE), and 2D and 3D gradient echo
      (GE) sequences on 1.5 T and 3.0 T MR scanners. The images were analyzed by two
      independent radiologists in a blinded manner, by dividing the patella into 15
      virtual segments. The results were correlated with the macropathologic findings
      with regards to location, width, and depth of the defects. RESULTS: The highest
      sensitivity (67.1 %), diagnostic accuracy (85.4 %), positive (87.3 %), and
      negative (84.7 %) predictive values in detecting defects were obtained using the
      3.0 T FS-3D-GE sequence. The highest specificity (95.6 %) yielded the 3.0 T FS-2D
      GE sequence, with the other sequences inferior by no more than 2.6 %. In general,
      FS-3D-GE sequences were superior to FS-2D-GE (3.0 T: p < 0.05; 1.5 T: p < 0.05)
      and especially to FS-PD-FSE sequences (3.0 T: p < 0.01; 1.5 T: p < 0.05). In
      determining the defects' widths, the 3.0 T FS-3D-GE sequence was superior to all
      other sequences (correct measurements: 50.0 %), with only slight superiority to
      the 1.5 T FS-3D-GE sequence (46.9 %, p > 0.05) but clear superiority to the other
      sequences (28.1 - 40.6 %, vs. 1.5 T FS-PD-FSE: p < 0.05, vs. other sequences: p >
      0.05). To determine the defects' depths, the 1.5 T FS-3D-GE sequence was most
      reliable (correct measurements: 53.1 %), followed by the 3.0 T FS-3D-GE sequence
      (50.0 %, significance of difference: p > 0.05). CONCLUSION: In detecting
      cartilage defects, the field strength of 3.0 Tesla was only superior to 1.5 T MRI
      using fat-saturated 3D- or 2D-GE-sequences but not in fat-saturated proton
      density-weighted SE-sequences. In determination of depth and length of the
      defects, the higher field strength was not advantageous.

PMID- 15497087
TI  - [Image quality of thin- and thick-slice MSCT reconstructions in low-contrast
      objects (liver lesions) with equal doses].
AB  - PURPOSE: To evaluate the image quality of thin-section MSCT examinations of low
      contrast objects such as liver lesions, and to find out whether a thin slice
      technique requires an increase in radiation dose. MATERIALS AND METHODS: MSCT
      examinations of the liver were performed in the portal venous phase on a Volume
      Zoom Scanner (Siemens, Erlangen) with a collimation of 4 x 2.5 mm, 120 kV, 125
      mAs and table speed of 12.5 mm. Forty small hypodense liver lesions with a mean
      size of 3 mm (1 to 8 mm) were reconstructed using a slice thickness of 3, 5, 7,
      and 10 mm. All lesions were evaluated for each slice thickness by 3 independent
      radiologists using a 5-point scale (excellent to poor) for the following 7
      criteria: contrast, demarcation and contour of the lesion, image noise and
      quality, demarcation of liver veins and liver contour. The mean values of the
      reviewers' scores were calculated. The correlation of the three observers in the
      evaluation of the criteria was determined using the Kendall's Tau coefficient.
      RESULTS: The 3-mm thin sections were excellent in the evaluation of lesion
      detection, lesion contrast and lesion contour with a mean score of 1.4 compared
      to 4.1 for 10-mm sections. Concerning the criteria image quality and liver
      contour, thin sections achieved the best results in our series. Image noise was
      pronounced in thin sections but did not affect negatively the image analysis.
      Interrater agreement was 0.53 for the criterium image noise. CONCLUSION: Thin
      sections in MSCT examinations of low contrast objects such as liver lesions do
      not require an increase in radiation dose because the increase in image noise is
      compensated by improved lesion contrast.

PMID- 15497088
TI  - [5 years of "concerted action dose reduction in CT" -- what has been achieved and
      what remains to be done?].
AB  - In May 1998, the German "Concerted Action Dose Reduction in CT" was founded by
      all parties involved in CT. Its intention was to achieve a significant reduction
      of the radiation exposure caused by CT, a matter that has increasingly been
      considered a major challenge since the early nineties. As a result of a number of
      joint efforts, the essential preconditions have been established by now. The
      fifth anniversary of the Concerted Action gave rise for both retrospection and
      outlook on the tasks that have already been accomplished and those that still
      need to be done. For this purpose, a one-day symposium took place in Berlin on
      November 4, 2003. The contents of a total of 18 contributions will be outlined
      here in brief.

PMID- 15497089
TI  - [Initial experiences with a laser-supported, integrated into the CT-gantry target
      system, when executing CT-controlled functions].

PMID- 15497090
TI  - [Renal vein thrombosis that did not exist].

PMID- 15497091
TI  - [Glioblastoma multiforme of the optic nerve].

PMID- 15497093
TI  - Application of flow cytometry to platelet disorders.
AB  - Flow cytometry is a powerful and versatile tool that can be used to yield
      definitive information regarding the phenotypic status of platelets. The method
      provides a quantitative assessment of the physical and antigenic properties of
      platelets (e.g., surface expression of receptors, bound ligands, components of
      granules, or interactions of platelets with other platelets, other blood cells,
      or components of the plasma coagulation system), thereby facilitating the
      diagnosis of inherited or acquired platelet disorders (e.g., Bernard-Soulier
      syndrome, Glanzmann thrombasthenia, storage pool disease), the pathological
      activation of platelets (e.g., in the setting of acute coronary syndromes,
      cerebrovascular ischemia, peripheral vascular disease, cardiopulmonary bypass),
      and changes in the ability of platelets to activate via specific stimuli (e.g.,
      efficacy of antiplatelet therapies). Accordingly, this review summarizes the key
      technical and methodologic components of flow cytometric analysis of platelets,
      as well as specific examples of its application to diagnosis and patient care.

PMID- 15497094
TI  - Inherited thrombocytopenias: molecular mechanisms.
AB  - Each megakaryocyte forms 10(3) platelets and 10(11) platelets are replenished
      daily. The unique and amazing mechanisms that allow megakaryocytes to become
      giant and polyploid and to release such a large number of platelets are still
      poorly understood. The study of inherited thrombocytopenias offers the
      possibility to gain new information on these processes because several different
      forms, deriving from defective megakaryocytic commitment, differentiation,
      maturation, or platelet formation, have been identified. Moreover, in the
      presence of some genetic defects, megakaryocytes produce platelets with a
      shortened life span. In this review, we summarize what we have learned about
      inherited thrombocytopenias in the last few years.

PMID- 15497095
TI  - Inherited defects in platelet signaling mechanisms.
AB  - In the majority of patients with an inherited abnormality in platelet function
      and a bleeding diathesis, the underlying platelet molecular mechanisms are
      unknown. The usually considered entities, such as thrombasthenia, the Bernard
      Soulier syndrome, and storage pool deficiency, occur in a small proportion of
      patients. A substantial number of patients present with decreased aggregation and
      secretion of dense granule contents upon activation, and are lumped in the
      category of primary secretion defects or platelet activation defects. Evidence is
      now available that defects in platelet signaling mechanisms may be the basis for
      the platelet dysfunction in some of these patients. This evidence is presented
      here. If the key components in signal transduction are the surface receptors, the
      G-proteins, and the effectors, evidence now exists for specific human platelet
      abnormalities at each of these levels. There is a pressing need for a concerted
      effort to delineate the molecular mechanisms in the large group of patients with
      impaired platelet function who represent an untapped reservoir of new information
      into normal platelet function.

PMID- 15497096
TI  - Molecular defects that affect platelet dense granules.
AB  - Platelet dense granules form using mechanisms shared by melanosomes in
      melanocytes and by subsets of lysosomes in more generalized cells. Consequently,
      disorders of platelet dense granules can reveal how organelles form and move
      within cells. Models for the study of new vesicle formation include isolated
      delta-storage pool deficiency, combined alphadelta-storage pool deficiency,
      Hermansky-Pudlak syndrome (HPS), Chediak-Higashi syndrome, Griscelli syndrome,
      thrombocytopenia absent radii syndrome, and Wiskott-Aldrich syndrome. The
      molecular bases of dense granule deficiency are known for the seven subtypes of
      HPS, as well as for Chediak-Higashi syndrome, Griscelli syndrome, and Wiskott
      Aldrich syndrome. The gene products involved in these disorders help elucidate
      the generalized process of the formation of vesicles from extant membranes such
      as the Golgi.

PMID- 15497097
TI  - Molecular mechanisms in thrombotic thrombocytopenic purpura.
AB  - Thrombotic thrombocytopenic purpura (TTP) is characterized by thrombocytopenia
      and microangiopathic hemolysis. Unlike the typical hemolytic uremic syndrome
      (HUS), which follows infection with shiga toxin-producing microorganisms, most
      cases of TTP do not have an obvious etiology. Recent studies revealed that a
      plasma zinc metalloprotease ADAMTS (a disintegrin and metalloprotease with
      thrombospondin type 1 motif) 13 cleaves von Willebrand factor in a shear
      dependent manner. Deficiency of ADAMTS13, due to autoimmune inhibitors of the
      protease or genetic mutation in the ADAMTS13 gene, results in a propensity to the
      development of von Willebrand factor-platelet aggregation and intravascular
      thrombosis characteristic of TTP. The identification of the molecular defect in
      TTP raises the prospect that this hitherto mysterious disorder will be managed
      with a more rationally designed strategy in the near future.

PMID- 15497098
TI  - Heparin-induced thrombocytopenia and other immune thrombocytopenias: lessons from
      mouse models.
AB  - The prototype immune thrombocytopenia is (auto)immune thrombocytopenic purpura,
      ITP. The major issues in the pathophysiology, diagnosis, and therapy of ITP are
      presented. Mouse models of the pathophysiology of ITP have allowed greater
      understanding of the role of antiplatelet antibodies and of antibody effector
      mechanisms. In addition, there has been a substantial increase in interest in the
      use of mouse models to understand the mechanisms of action of therapeutics for
      ITP, with notable progress for intravenous immunoglobulin (IVIG) and anti-red
      blood cell therapies. The immune-mediated thrombocytopenia and thrombosis
      syndromes are a common cause of morbidity and mortality; the prototype is heparin
      induced thrombocytopenia and thrombosis (HITT). There has been substantial
      progress in understanding the pathophysiology, diagnosis, and therapy of HITT in
      the last decade, but there remain major questions. The four necessary and
      sufficient elements for HITT in vivo were established in our mouse model (namely
      platelet factor 4 [PF4], heparin, antibody to the heparin/PF4 complex, and
      platelet Fc receptor for immunoglobulin G [FcgammaRIIa]). Currently, our HITT
      mouse models are being used to address a number of questions. For example, what
      are the roles of antibody titer, isotype, and epitope targets? Are there genetic
      determinants of platelet activation, such as the platelet FcgammaRIIa receptor
      density, operable in HITT? What are the roles of tissue factor/factor VIIa
      (TF/VIIa), monocytes, and blood cell-derived microparticles? What is the
      contribution of pre-existing endothelial cell (EC) dysfunction, and/or induced EC
      dysfunction? As in many human disorders, preclinical mouse models will continue
      to be important in the immune thrombocytopenia syndromes to achieve translation
      into improved patient care.

PMID- 15497099
TI  - Thrombocytopenia resulting from sensitivity to GPIIb-IIIa inhibitors.
AB  - Agents that inhibit the binding of fibrinogen to its platelet receptor
      (glycoprotein [GP] IIb-IIIa, alpha(IIb)/beta3 integrin) constitute a promising
      new group of antithrombotic drugs. Acute thrombocytopenia, often occurring within
      a few hours of starting treatment, is a recognized side effect of this family of
      compounds. Although most affected patients recover uneventfully, severe bleeding
      and fatal outcomes have been described. Both nonimmune and immune mechanisms have
      been implicated in the pathogenesis of this complication, but accumulating
      evidence suggests that drug-dependent antibodies are responsible for platelet
      destruction in many (and perhaps most) affected individuals. These antibodies are
      unique in that they can be present in persons not previously exposed to a GPIIb
      IIIa inhibitor, allowing for the possibility that thrombocytopenia can occur
      within hours of starting treatment. Additional studies are needed to more fully
      define the characteristics of these antibodies and to identify risk factors that
      predispose patients to this complication.

PMID- 15497100
TI  - Platelet dysfunction in renal failure.
AB  - Patients with end-stage renal disease suffer from complex hemostatic disorders.
      Uremic patients show a bleeding diathesis that is mainly due to abnormalities of
      primary hemostasis; in particular, platelet dysfunction and impaired platelet
      vessel wall interaction. However, despite decreased platelet function, these
      patients have a high prevalence of cardiovascular and thrombotic complications.
      Platelet dysfunction in uremic patients is partially due to uremic toxins present
      in circulating blood. Dialysis improves platelet abnormalities and reduces, but
      does not eliminate, the risk of hemorrhage. Hemodialysis can even contribute to
      the bleeding through the continuous platelet activation induced by the
      interaction between blood and artificial surfaces. Thrombocytopenia, glomerular
      thrombosis, and thrombi in small arteries and glomerular capillaries are common
      pathological features in many renal diseases. Platelets are also involved
      directly in the pathogenesis of glomerular diseases through a variety of
      mechanisms, including release of active molecules, by enhancing immune complex
      deposition, and by altering glomerular permeability.

PMID- 15497101
TI  - Clinical and functional consequences of platelet membrane glycoprotein
      polymorphisms.
AB  - The last several years have seen an abundance of studies of genetic risk factors
      for vascular disease, and platelet glycoprotein (GP) polymorphisms have been a
      primary focus of this area of research. This article reviews GP receptor
      polymorphisms, particularly those on GPIa-IIa (integrin alpha2beta1), GPIb-IX-V,
      GPIIb-IIIa (integrin alpha(IIb)beta3), and GPVI, and summarizes clinical and
      functional studies that have attempted to clarify their roles in human disease.
      Our focus is on recent work relevant to thrombotic and hemostatic processes and
      advances in pharmacogenetics. We consider issues affecting our ability to derive
      firm conclusions from these studies, and discuss future directions in this
      rapidly evolving area.

PMID- 15497102
TI  - [Shared decision making].
AB  - BACKGROUND AND OBJECTIVE: The demand for integration of patients in medical
      decisions becomes more and more obvious. Little is known about whether patients
      are willing and ready to share therapeutic decisions. So far information is
      lacking, whether existing communication skills of both -- patients and physicians
      -- are sufficient for shared decision making (SDM). This paper presents new data
      on patients perspectives regarding SDM. METHODS: Standardized survey of 3058
      German speaking people (1565 females, 1493 males), aged 18-79 years, a population
      based random sample of an access panel (pool of german households available for
      specific surveys) regarding the following topics: medical decision making in
      practice, communication skills and behaviour of physicians. RESULTS: A majority
      of patients approved the model of SDM. However, some subgroups of patients,
      especially older patients, were less interested in the concept of SDM. Necessary
      communication skills which may help patients to participate in decision making
      were used rather scarcely. Patients who approved the model of SDM more often
      experienced a common and trustful exchange of information. CONCLUSION: Most
      patients favour the concept of SDM. The communication skills necessary for this
      process are to be promoted and extended. Research on patients' preferences and
      their participation in health care reform should be intensified. Academic and
      continuous medical education should focus on knowledge transfer to patients.

PMID- 15497103
TI  - [Left ventricular apical ballooning].
AB  - HISTORY: A 40-year-old woman and a 50-year-old man were admitted with acute chest
      pain indicative of an acute coronary syndrome. INVESTIGATIONS: In addition to ECG
      changes suggestive of acute ischemia and a minor increase in the serum
      concentration of troponin-I both patients had a severely reduced left ventricular
      function with extensive apical akinesis on echocardiography (LV- ejection
      fraction 20, respectively 40%). Stenotic coronary artery disease was excluded by
      coronary angiography, however left ventriculography showed a "ballooned" apex
      resembling an aneurysm. DIAGNOSIS, TREATMENT AND COURSE: Both patients were
      observed and treated symptomatically in the intensive care unit. Within four
      weeks the LV-function had completely recovered in both patients. Both patients
      had an atypical acute coronary syndrome as indicated by electrocardiographic
      signs of ischemia and serological markers. After perusal of the relevant
      literature the diagnosis of "apical ballooning" based on the finding of a
      "ballooned" akinesis of the left ventricular apex in the absence of coronary
      artery stenosis or a reasonable alternative cause of myocardial ischemia was
      made. The aneurysm-like left ventricular dysfunction is fully reversible without
      specific treatment. CONCLUSION: Left apical ballooning is a rare, but
      increasingly recognized diagnosis in patients presenting with the clinical
      picture of cardiac ischemia in the absence of coronary artery disease. The
      pathogenesis of the LV-dysfunction, which is reversible, is not known and the
      prognosis is good in patients who survive the initial period of severe
      ventricular dysfunction.

PMID- 15497104
TI  - [Hypothenar hammer syndrome as a cause of severe digital ischemia].
AB  - HISTORY AND CLINICAL FINDINGS: A 69-year-old amateur carpenter complained of a
      sudden stabbing pain and a white discoloration of D4 and D5 of the right hand
      while shoveling snow. On admission in our clinic twelve days later, clinical
      inspection showed a gangrene of the distal bone of D5 and proximal garland-shaped
      radial and ulnar subcutaneous haemorrhage and already ischemic contracture. D4
      showed pale livid colour. INVESTIGATIONS: According to the results of an
      arteriography acral pulse oscillography revealed a occlusion of the digital
      arteries. Duplex sonography showed a thrombotic occluded aneurysm of the right
      ulnar artery over the hypothenar area. DIAGNOSIS: Hypothenar hammer syndrome with
      a thrombotic occlusion of an aneurysm of the distal ulnar artery and multiple
      thromboembolic occlusions of the digital arteries of D4 and D5 of the right hand.
      TREATMENT AND COURSE: After initial therapy with Iloprost, treatment of pain and
      local treatment, an intraarterial locoregional lysis therapy with urokinase was
      performed. Acral blood circulation improved significantly and the patient was
      completely painless after treatment. CONCLUSION: In case of an acute onset of
      unilateral digital ischemia hypothenar hammer syndrome should be considered.
      Regional thrombolysis can be performed in case of severe digital ischemia.

PMID- 15497105
TI  - [Growth hormone-receptor antagonist pegvisomant].

PMID- 15497106
TI  - [Rational therapy of urolithiasis in every-day practice].
AB  - Patients with renal colic are usually treated in emergency care units or by their
      family doctors and require immediate diagnosis and treatment. The life-time risk
      is up to 10 %. The prevalence amounts to 4.7 % in Germany. In addition to
      confirming the diagnosis and inducing an adequate pain therapy it's very
      important for patients to be directed correctly and, above all, prevention is
      important, too. Without treatment the recurrence rate ranges between 50 and 100
      %. Particularly, these principals should give useful advice, wherever patients
      are treated without urological department.

PMID- 15497108
TI  - [Competitors' complaint of the residents against the authorization of hospital
      physicians to contract medical care. Decision of the Federal Constitutional
      Court, 8/17/2004].

PMID- 15497109
TI  - ["Adult form" of congenital liver fibrosis].

PMID- 15497107
TI  - [Adjuvant therapy for colon cancer].

PMID- 15497110
TI  - [ACE inhibitor therapy until end of life?].

PMID- 15497112
TI  - Current issues in diagnosis and treatment of primary and metastatic brain tumors.

PMID- 15497113
TI  - Altered molecular pathways in gliomas: an overview of clinically relevant issues.
AB  - Primary central nervous system (CNS) tumors constitute a small fraction of the
      overall incidence of human cancer, but they represent a major source of cancer
      related morbidity and mortality. The most common CNS tumor subtype in adults,
      high-grade astrocytoma, confers a dismal prognosis with a median survival of only
      1 to 2 years. Other common adult CNS tumors, ie, low-grade astrocytomas and
      oligodendrogliomas, carry a less ominous, yet still poor prognosis.
      Unfortunately, there has been little progress in extending the survival or
      quality of life for glioma patients, despite nearly four decades of extensive
      research. This research has, however, greatly increased our understanding of the
      underlying molecular biology of these tumors, examples of which include the
      determination of elevated epidermal growth factor receptor (EGFR) as well as
      platelet-derived growth factor receptor (PDGF) signaling, and the inactivation of
      p53 , p16 , and PTEN tumor-suppressor genes (TSGs) that negatively regulate
      specific enzymatic activities in normal glial cells. Such observations have
      greatly improved our understanding of the pathogenesis of these tumors and have
      potential diagnostic as well as therapeutic relevance. With respect to the latter
      of these two issues, the identification of aberrant enzymatic activities in
      gliomas has promoted the development of novel therapeutic agents that target
      specific signaling effectors, and whose inhibition should, in theory, prove to be
      cytostatic, if not cytotoxic, to tumor cells. Several clinical trials are
      currently underway for testing these therapeutic agents in patients with primary
      brain tumors, and it is hoped that the targeting of pro-tumorigenic enzymatic
      activities will lead to better patient outcomes. In this review, we will describe
      the most pertinent genetic and signaling pathway alterations that are clinically
      relevant to the management of glial tumors.

PMID- 15497111
TI  - Attention-deficit/hyperactivity disorder in a population isolate: linkage to loci
      at 4q13.2, 5q33.3, 11q22, and 17p11.
AB  - Attention-deficit/hyperactivity disorder (ADHD [MIM 143465]) is the most common
      behavioral disorder of childhood. Twin, adoption, segregation, association, and
      linkage studies have confirmed that genetics plays a major role in conferring
      susceptibility to ADHD. We applied model-based and model-free linkage analyses,
      as well as the pedigree disequilibrium test, to the results of a genomewide scan
      of extended and multigenerational families with ADHD from a genetic isolate. In
      these families, ADHD is highly comorbid with conduct and oppositional defiant
      disorders, as well as with alcohol and tobacco dependence. We found evidence of
      linkage to markers at chromosomes 4q13.2, 5q33.3, 8q11.23, 11q22, and 17p11 in
      individual families. Fine mapping applied to these regions resulted in
      significant linkage in the combined families at chromosomes 4q13.2 (two-point
      allele-sharing LOD score from LODPAL = 4.44 at D4S3248), 5q33.3 (two-point allele
      sharing LOD score from LODPAL = 8.22 at D5S490), 11q22 (two-point allele-sharing
      LOD score from LODPAL = 5.77 at D11S1998; multipoint nonparametric linkage [NPL]
      log[P value] = 5.49 at approximately 128 cM), and 17p11 (multipoint NPL-log [P
      value] >12 at approximately 12 cM; multipoint maximum location score 2.48 [alpha
      = 0.10] at approximately 12 cM; two-point allele-sharing LOD score from LODPAL =
      3.73 at D17S1159). Additionally, suggestive linkage was found at chromosome
      8q11.23 (combined two-point NPL-log [P value] >3.0 at D8S2332). Several of these
      regions are novel (4q13.2, 5q33.3, and 8q11.23), whereas others replicate already
      published loci (11q22 and 17p11). The concordance between results from different
      analytical methods of linkage and the replication of data between two independent
      studies suggest that these loci truly harbor ADHD susceptibility genes.

PMID- 15497114
TI  - Proton magnetic resonance spectroscopic evaluation of brain tumor metabolism.
AB  - Magnetic resonance imaging (MRI) is the neuroimaging method of choice for the
      noninvasive monitoring of patients with brain tumors due to the enormous amount
      of information it yields regarding the morphologic features of the lesion and
      surrounding parenchyma. Over the past decade, proton magnetic resonance
      spectroscopy (1H-MRS), which uses the same technology as MRI and can be performed
      during a routine clinical imaging examination, has been used to glean information
      about the metabolic status of the brain. Accurate interpretation of 1H-MRS data
      from individual patients requires an understanding of the various techniques for
      acquiring the data, the physiologic basis of the metabolic signatures obtained
      from different types of tumors, and the specificity of the technique. This review
      covers the basic physics of 1H-MRS, the spectral and physiological
      characteristics of the metabolites that are typically measured in various types
      of brain tumors, and the clinical utility of 1H-MRS with respect to diagnosis,
      therapeutic planning, and the assessment of response to treatment.

PMID- 15497115
TI  - Anaplastic astrocytoma: diagnosis, prognosis, and management.
AB  - The designation of a tumor as anaplastic astrocytoma (AA) reflects a distinct
      histologic classification of malignant glioma characterized by an abundance of
      pleomorphic astrocytes with evidence of mitosis. Although these tumors are
      malignant, they have a better prognosis and a higher likelihood of response to
      treatment than glioblastoma. Despite advances in brain tumor imaging, making an
      accurate diagnosis requires the evaluation of tumor tissue and is essential for
      treatment planning. Currently, most patients undergo maximal surgical debulking
      of tumor followed by external beam radiation, often with subsequent adjuvant
      chemotherapy. However, despite the use of these treatment modalities, most tumors
      recur within a few years and these recurrent tumors are more refractory to
      subsequent therapies. This review examines the diagnosis, prognosis, and
      treatment of AAs. Ongoing clinical research investigations are also summarized,
      reflecting advances in our knowledge of the molecular pathogenesis of these
      tumors and providing hope for significant improvements in patient outcomes.

PMID- 15497116
TI  - Current management of glioblastoma multiforme.
AB  - Glioblastoma multiforme is the most common primary brain tumor in adults. Despite
      major research efforts and progress in neuroimaging, neurosurgery, and radiation
      and medical oncology, the overall survival of patients with this disease has
      changed little over the past 30 years. Surgery and radiation therapy remain
      critical components in the care of patients with glioblastoma multiforme.
      Treatment with chemotherapy has been hampered by the apparent resistance of these
      tumor cells to available agents and challenges in delivering agents to the tumor
      cells. The blood-brain barrier can restrict entry of some agents and the effect
      of antiepileptic drugs inducing hepatic P450 can significantly affect the
      pharmacology of a wide range of antineoplastic agents. As a result, new agents
      and novel approaches are required. Translational research efforts should: (1)
      pursue a broad research agenda until productive avenues are identified; (2)
      quantify the delivery of novel agents to the malignant brain tumor cells; (3)
      determine the maximum tolerated dose (MTD) and preliminary efficacy data on novel
      agents before initiating combination therapies; (4) optimize trial designs; and
      (5) improve psychosocial and supportive care for patients with this devastating
      illness.

PMID- 15497117
TI  - Diagnosis and management of oligodendroglioma.
AB  - The discovery of the sensitivity to chemotherapy of oligodendroglial tumors has
      greatly increased the interest in this tumor type. After the first studies
      showing the activity of chemotherapy with procarbazine, lomustine (CCNU), and
      vincristine (PCV), it is now clear that temozolomide is also effective in this
      tumor type. Fifty percent to 70% of patients with recurrent oligodendroglial
      tumors may respond to chemotherapy. The histological diagnosis of
      oligodendroglial tumors is still subject to a significant observer bias. This
      variation appears to be one of the causes of the recent relative increase in
      incidence of oligodendroglial tumors. Genetically, 60% to 70% of oligodendroglial
      tumors are characterized by the loss of the short arm of chromosome 1 (1p) and
      the loss of the long arm of chromosome 19 (19q). Virtually all tumors with the
      combined loss of 1p/19q respond to chemotherapy, which has been the first
      demonstration of the clinical usefulness of the genotyping of brain tumors. These
      tumors also more often have a classical oligodendroglial histology and have a
      much better prognosis than oligodendrogliomas without 1p/19q loss. Although the
      belief is widely held that in the near future the genotype of oligodendroglial
      tumors may help in selecting patients for treatment, this assumption has not been
      proven. Prospective trials on oligodendroglial tumors with analyses of the
      genotype are needed before such conclusions can be drawn. In the meantime it is
      clear that ultimately all patients with oligodendroglial tumors die of their
      disease, and that novel treatments are required to improve prognosis. For an
      improved prognosis, a better understanding of the aberrant pathways and the
      driving force behind these tumors is required.

PMID- 15497118
TI  - Current controversies in the radiotherapeutic management of adult low-grade
      glioma.
AB  - Over the last decade, the results of four prospective clinical trials of
      supratentorial low-grade glioma (LGG) in adults have been published. The data
      from the nearly 1,000 patients treated on these studies are summarized in this
      presentation, addressing the following three current controversies in the
      radiotherapeutic management of these patients: (1) optimum timing of radiation
      therapy (RT); (2) optimum RT dose; and (3) addition of chemotherapy to RT. The 5
      year overall survival (OS) and progression-free survival (PFS) rates in these
      four studies ranged from 58% to 72% and from 37% to 55%, respectively.
      Significant prognostic factors included extent of surgical resection, histology,
      tumor size, and age. The European Organization for Research and Treatment of
      Cancer (EORTC) study 22845 randomized 311 adults to postoperative observation or
      RT. There was no difference in the 5-year OS rate between the two arms, but the
      irradiated patients had a significantly improved 5-year PFS rate. EORTC study
      22844 randomized 379 adults to low- versus high-dose RT. Similarly, an intergroup
      study conducted by the North Central Cancer Treatment Group (NCCTG), Radiation
      Therapy Oncology Group (RTOG), and Eastern Cooperative Group (ECOG) randomized
      211 adults to low- versus high-dose RT. There was no difference in the 5-year OS
      or PFS rates between the two dose groups in either study. A Southwest Oncology
      Group (SWOG) study randomized 60 adults with incompletely resected LGG to RT
      alone or RT plus lomustine (CCNU) chemotherapy. There was no difference in
      outcome between the two treatment arms. Further prospective clinical trials are
      needed to define the optimal management strategy for adults with supratentorial
      LGG. The schemata from recently completed and ongoing LGG studies will be
      presented.

PMID- 15497119
TI  - Advances in neurosurgical technique in the current management of brain tumors.
AB  - Despite significant advances in anatomical and functional neuroimaging modalities
      (eg, magnetic resonance [MR] imaging [MRI], MR spectroscopy [MRS], diffusion and
      perfusion MR, functional MRI [fMRI], magnetic-source imaging [MSI], diffusion
      tensor imaging [DTI]) and neuronavigation techniques, intraoperatively obtained
      functional information remains of crucial importance to the neurosurgeon,
      especially when operating on tumors that are located in or adjacent to functional
      cortical sites and subcortical pathways. This article focuses on recent advances
      in the surgical management of of intracerebral tumors with special emphasis on
      intraoperative cortical and subcortical stimulation mapping methods, and the
      prognostic significance of surgery on patient outcome.

PMID- 15497120
TI  - Current treatment of medulloblastoma: recent advances and future challenges.
AB  - Medulloblastoma (MB) is the most common malignant brain tumor of childhood, yet
      it makes up only 1% of adult brain tumors. MB is uniquely sensitive to
      chemotherapy and radiation, but successful surgical resection continues to be an
      important component of therapeutic success. Progress in the treatment of MB has
      occurred in multiple areas from improved neurosurgical techniques, refined dosing
      and delivery of radiation, and optimized chemotherapy. Tumors are currently risk
      stratified as average risk or high risk depending on clinical factors such as
      age, extent of resection, and presence of metastases. Molecular biology is
      beginning to improve upon clinical prognostication and may soon provide the means
      to accurately predict response to therapy. Treatment for average-risk MB has
      achieved a level of success that allows efforts to be focused on the limitation
      of adverse treatment effects. Therapy for high-risk and relapsed MB has been
      positively affected by the advent of high-dose chemotherapy with stem cell
      rescue. In addition, molecular targets are being elucidated and new therapeutic
      agents are being tested for safety and efficacy. Treatment for this disease has
      evolved a great deal over the preceding decades, but a great deal of work remains
      to be done to effect reliable cures while reducing long-term sequelae of therapy.

PMID- 15497121
TI  - Clinical management of primary central nervous system germ cell tumors.
AB  - Despite excellent long-term results for patients with germinoma treated with
      radiation therapy, the potential for late effects makes the treatment
      controversial. On the other hand, most patients with non-germinomatous tumors
      treated by conventional treatment with surgery and radiation therapy fail to
      survive longer than 3 years. After combination chemotherapy with cisplatin was
      confirmed to be effective in gonadal germ cell tumors, germ cell tumors of the
      brain became candidates for chemotherapy. The author reviews several prospective
      phase II studies that are being investigated to assess the effect of combination
      chemotherapy and radiation therapy for germ cell tumors. The aim of these studies
      is to reduce the volume and dose of radiation therapy for germinoma and prolong
      the survival of patients of non-germinomatous tumors. For germinoma, a trial with
      chemotherapy alone failed, with a high rate of recurrence, but Japanese and
      European trials with reduced-dose chemotherapy and a smaller volume of radiation
      therapy have resulted in high event-free survival (EFS) rates. Ongoing phase II
      studies with combined chemotherapy and radiation therapy for non-germinomatous
      tumors will result in a 5-year survival rate of greater than 50%, which is better
      than that achieved by radiation therapy alone.

PMID- 15497122
TI  - Treatment of primary central nervous system lymphoma.
AB  - Primary central nervous system lymphoma (PCNSL) is a rare neoplasm that has
      captured popular attention because of its rising incidence and marked
      chemosensitivity. It is a non-Hodgkins B-cell lymphoma (NHL) that appears
      confined to the central nervous system (CNS) at presentation but may be
      multifocal within the brain or involve the leptomeninges or eyes at diagnosis.
      Like systemic lymphoma, it is highly sensitive to corticosteroids, and
      administration of steroids should be withheld until the diagnosis has been
      confirmed histologically. Currently, the initial treatment of choice incorporates
      high-dose methotrexate (HD-MTX) either as a single agent or in combination with
      other systemic chemotherapies. Whole-brain radiotherapy (WBRT) can be a highly
      effective treatment modality when combined with MTX, but the combination causes
      an unacceptably high incidence of severe permanent neurotoxicity, particularly in
      patients over age 60. Therefore, chemotherapy alone is the initial treatment of
      choice in older patients. This approach is also being explored in younger
      patients, but it is possible that deferring radiotherapy may compromise disease
      control. Consequently, the role of radiotherapy remains to be clarified in newly
      diagnosed younger patients with PCNSL.

PMID- 15497123
TI  - Management of brain metastases.
AB  - Patients with brain metastases have a generally poor outcome with a median
      survival after diagnosis of approximately 4 months. Management of brain
      metastases involves symptomatic treatment and definitive therapy, with the goal
      of stabilizing and improving neurologic function and survival. Traditional and
      novel therapies, including whole-brain radiation therapy (WBRT), surgery,
      radiosurgery, radiosensitizers, and chemotherapy are reviewed. The results of
      important clinical trials are discussed. In addition, current controversies in
      the management of brain metastases, such as the choice of surgery or radiosurgery
      for resectable lesions and the possible avoidance of (WBRT), are highlighted.

PMID- 15497124
TI  - Cognitive sequelae of brain radiation in adults.
AB  - Radiotherapy (RT) is a proven curative and palliative therapeutic tool in the
      treatment of a wide variety of primary and metastatic brain tumors in adults.
      Recent advances in multimodality therapy have led to improvement in survival for
      many cancer patients. As survival has improved, more attention has been directed
      toward long-term treatment-related morbidity. Specifically, the effect of RT on
      the long-term cognitive performance of these patients is a major concern. This
      article reviews the neurocognitive effects of cranial RT on adult patients with
      brain tumors. Analyses of neurocognitive function are confounded by factors such
      as surgery, chemotherapy, tumor characteristics, tumor progression, concurrent
      medical illnesses, neurologic comorbidity, and medications that can contribute to
      neurocognitive deficits. Risk of deficits after cranial RT is associated with
      high RT dose, large fraction size, larger field size, and extremes of age at time
      of treatment. Using modern techniques with moderate total doses (50 to 54 Gy),
      conformal RT, conventional fractionation, and advanced planning imaging and
      software, the risks of neurocognitive deficits are quite small and greatly
      overshadowed by deficits caused by the tumor itself. Further studies need to be
      undertaken to elucidate the degree and cause of cognitive decline in adult
      patients undergoing multimodality therapy for cranial tumors.

PMID- 15497125
TI  - Progress in modulating the RBC membrane to produce transfusable universal/stealth
      donor RBCs.
AB  - Two approaches have been used to produce red blood cells (RBCs) that could be
      transfused, regardless of the ABO group of the donor and recipient, the so-called
      "universal donor" RBCs. The first approach has involved converting group A and B
      RBCs to group O by cleaving off the terminal immunodominant sugars; the second
      approach involves masking the A and B antigens with polyethylene glycol (PEG).
      The latter approach has also been used to mask all other blood group antigens on
      the RBC membrane, yielding so-called "stealth RBCs"; the hope is that such
      PEGylated RBCs (PEG-RBCs) will not react with any blood group antibodies and may
      not be recognized as foreign, thus not initiating an immune response. The former
      approach is well advanced. Clinical trials have shown that units of group B blood
      converted to group O, using a galactosidase, survived normally without any ill
      effects to recipients. Work is progressing on the efficient conversion of group A
      RBCs to group O. PEG-RBCs can be prepared that will not react with any blood
      group antibodies in vitro, but RBC survival in animals has not been good. Recent
      data show that PEG is immunogenic and can induce antibodies that shorten survival
      of transfused PEG-RBCs in rabbits.

PMID- 15497126
TI  - Improving technology for collecting platelets by apheresis: five-year experience
      in one blood center.
AB  - Over the past decade, newly introduced methods for apheresis platelet collection
      have led to increased collection yields. This has resulted in "splitting," which
      allows transfusion of 2 patients from 1 high-yield collection. Although many
      small studies exist, no large studies have described the impact of methodological
      changes on routine blood center collections. We constructed a database containing
      selected parameters from 45,224 apheresis collections spanning July 1997 to April
      2002, using Gambro BCT Spectra (Lakewood, CO), Fenwal CS-3000+ (Baxter Healthcare
      Corp, Fenwal Division, Deerfield, IL), and Baxter Amicus instruments. A Baker
      9110+ hematology analyzer (Bio Chem Immunosystems, Inc., Allentown, PA) was used
      for platelet counting. Monthly average collection yields, distribution yields
      (product platelet contents after splitting), and split rates (the fraction of
      donations which may be split) were determined. The monthly mean collection yield
      and split rate correlated very closely. Both rose throughout the study period.
      The split rate climbed from 25% to 70% by study end. However, mean monthly
      distribution yields decreased by 7% because split and unsplit platelet yields
      both rose as split rates rose. Overcollections with the Amicus correlated with
      underestimation of donors' true preprocedure platelet counts during machine
      programming. Undercollections occurred in donors with low counts and, with-single
      needle Amicus, microcytic platelet collection. These results may assist in the
      optimization of an apheresis program. Increased collection yields correlated with
      cell separator type, dual-needle access, donor platelet count >250 x 10(9)/L,
      programming with true preprocedure platelet counts and capacity for triple
      product preparation from collection yields exceeding 2-bag storage capacity.

PMID- 15497127
TI  - Evidence-based practice of transfusion medicine: is it possible and what do the
      words mean?
AB  - Evidence-based medicine (EBM) optimizes clinical decision making by dictating
      that clinical decisions be based on the best available research evidence and by
      integrating best research evidence with clinical expertise and patient values.
      Several rankings of the strength of the evidence generated from different types
      of clinical research designs have been presented, and, in addressing a particular
      problem, clinicians can base their decision making on the types of clinical
      reports that have been published, along with an assessment of the strengths and
      weaknesses of each study. At a policy level, the concept of EBM would dictate
      that policy decisions also be made based on the best available research evidence.
      In transfusion medicine, however, decisions are based on a broader range of
      inputs, and the criteria for evaluating the efficacy and/or cost-effectiveness of
      proposed interventions differ from those used in other areas. Reasons why policy
      decisions are often based on considerations other than the best research evidence
      include public expectations about transfusion safety and proposals for applying
      the precautionary principle to transfusion medicine. Using the debate over the
      appropriateness of introducing universal white-cell reduction as an example, this
      review describes 2 perspectives for assessing evidence and/or making clinical or
      policy decisions: the evidence-based approach and the precautionary-principle
      approach; and also considers whether decisions in transfusion medicine can be
      truly evidence based.

PMID- 15497128
TI  - Fresh blood product manufacture, issue, and use: a chain of diminishing returns?
AB  - The available pool of potential blood donors continues to decrease. There are
      blood component losses all along the chain of production from the recruitment of
      the donor, attendance and bleeding of the donor, production process, storage of
      the inventory in the blood center, storage in the hospital or laboratory,
      selection, and transfusion of the recipient. There is a requirement and potential
      to improve product availability by better recruitment strategies, production
      methods, inventory management, and recipient selection. All of these areas of
      transfusion medicine have been investigated, and some data and options for
      improving donor/donation utilization are available in the literature. There are
      also some developing strategies that have the potential to have a positive
      influence on the availability of blood components. They include the use of blood
      components that have often been regarded as expensive. Further studies are
      required to determine if products such as leukoreduced red cells and platelets,
      unrefrigerated or fresh whole blood, and some recombinant products can conserve
      large numbers of other components or reduce hospital costs.

PMID- 15497129
TI  - Transfusion-transmitted tick-borne infections: a cornucopia of threats.
AB  - Over the past several decades, the frequency of contact between humans and ticks
      has increased dramatically. Concomitantly, several newly recognized tick-borne
      pathogens have emerged joining those already known to be transmitted by ticks.
      Together these factors have led to an enhanced public health awareness of ticks,
      tick-borne agents, and their associated diseases. Reports that several of these
      agents are transmitted by blood transfusion have raised concerns about blood
      safety. The primary agents of interest are members of the genus Babesia, but
      Anaplasma phagocytophilum, Rickettsia rickettsii, Colorado tick fever virus, and
      tick-borne encephalitis virus also have been transmitted by transfusion. In many
      cases, these agents and their diseases share common features including vectors,
      symptoms, and diagnosis. Unfortunately, they also share the common problem of
      insufficient epidemiologic and transmissibility data necessary for making
      informed decisions regarding potential blood safety interventions. Although
      further surveillance and epidemiologic studies of tick-borne agents are clearly
      needed, at present only the Babesia warrant consideration for active
      intervention; because donor management strategies based on risk-factor questions
      are inadequate, leukoreduction not effective for agents found in red cells and
      pathogen inactivation remains problematic for red cell products. Despite the
      present unavailability of screening assays, some form of serologic and nucleic
      acid testing may be justified for the Babesia. Given that interactions between
      humans and ticks are likely to increase in the future, vigilance is required as
      new and extant tick-borne agents pose potential threats to transfusion safety.

PMID- 15497131
TI  - The impact of diabetes on employment: genetic IVs in a bivariate probit.
AB  - Diabetes has been shown to have a detrimental impact on employment and labor
      market productivity, which results in lost work days and higher
      mortality/disability. This study utilizes data from the Border Epidemiologic
      Study on Aging to analyze the endogeneity of diabetes in an employment model. We
      use family history of diabetes as genetic instrumental variables. We show that
      assuming that diabetes is an exogenous variable results in an overestimate
      (underestimate) of the negative impact of diabetes on female (male) employment.
      Our results are particularly relevant in the case of populations where genetic
      predisposition has an important role in the etiology of diabetes.

PMID- 15497132
TI  - Thermosensitivity of optically active hydrogels constructed with N-(L)-(1
      hydroxymethyl)propylmethacrylamide.
AB  - We previously reported on the water soluble, optically active polymer, poly[N-(L)
      (1-hydroxymethyl)propylmethacrylamide] (P(L-HMPMA)), which has lower critical
      solution temperatures of approximately 30 and 21 degrees C upon heating and
      cooling, respectively. The phase separation behavior of the P(L-HMPMA)-water
      binary system has a reversible and clear hysteresis during heating and cooling
      cycles. The present study describes the thermosensitive properties of the
      optically active polymer and its hydrogel. Circular dichroism and
      microcalorimetric measurements of the polymer in water supported the hypothesis
      that the soluble polymer chains might be compactly folded with an interaction
      between optically active side chains. In addition, these measurements showed the
      polymer chains in a state of relatively low hydration compared to that of P(D,L
      HMPMA), which was free-radically synthesized from racemates of monomers. The
      solution properties reflected the swollen-shrunken behavior of corresponding
      hydrogels in response to temperature changes. The microscopic observation of
      aqueous polymer solutions and hydrogels also confirmed that the optically active
      properties of polymer chains affect their structure and thermosensitivity. SEM
      micrograph of the surfaces of the crosslinked P(L-HMPMA).

PMID- 15497133
TI  - Gluconic acid production in bioreactor with immobilized glucose oxidase plus
      catalase on polymer membrane adjacent to anion-exchange membrane.
AB  - Gluconic acid was obtained in the permeate side of the bioreactor with glucose
      oxidase (GOD) immobilized onto anion-exchange membrane (AEM) of low-density
      polyethylene grafted with 4-vinylpiridine. The electric resistance of the anion
      exchange membranes was increased after the enzyme immobilization on the membrane.
      The gluconic acid productions were relatively low with the GOD immobilized by any
      method on the AEM. To increase the enzyme reaction efficiency, GOD was
      immobilized on membrane of AN copolymer (PAN) adjacent to an anion-exchange
      membrane in bioreactor. Uses of anion-exchange membrane led to selective removal
      of the gluconic acid from the glucose solution and reduce the gluconic acid
      inhibition. The amount of gluconic acid obtained in the permeate side of the
      bioreactor with the GOD immobilized on the PAN membrane adjacent to the AEM under
      electrodialysis was about 30 times higher than that obtained with enzyme directly
      bound to the AEM. The optimal substrate concentration in the feed side was found
      to be about 1 g/l. Further experiments were carried out with the co-immobilized
      GOD plus Catalase (CAT) on the PAN membrane adjacent to the AEM to improve the
      efficiency of the immobilize system. The yield of this process was at least 95%.
      The storage stability of the co-immobilized GOD and CAT was studied (lost 20% of
      initial activity for 90 d). The results obtained clearly showed the higher
      potential of the dual membrane bioreactor with GOD plus CAT bound to
      ultrafiltration polymer membrane adjacent to the AEM. Storage stability of GOD
      activity in GOD plus CAT immobilized on PAN//AEM membranes and on AEM.

PMID- 15497134
TI  - High-throughput characterisation of materials by photoluminescence spectroscopy.
AB  - An automatic system for high-throughput (HT) characterisation of large libraries
      of solid materials by photoluminescence spectroscopy is described. The system
      provides time-resolved transient emission spectra in the microsecond scale and
      can be employed for characterisation of materials of interest in the fields of
      catalysis and electroluminescence, amongst others. Here, we present its
      application to the optimisation of the ship-in-a-bottle synthesis of a novel
      electroluminescent polymer (PPV) and a photocatalyst (TP+), both encapsulated in
      large-pore zeolites.

PMID- 15497135
TI  - Understanding sterol-membrane interactions part I: Hartree-Fock versus DFT
      calculations of 13C and 1H NMR isotropic chemical shifts of sterols in solution
      and analysis of hydrogen-bonding effects.
AB  - 1H and 13C NMR chemical shifts are exquisitely sensitive probes of the local
      environment of the corresponding nuclei. Ultimately, direct determination of the
      chemical shifts of sterols in their membrane environment has the potential to
      reveal their molecular interactions and dynamics, in particular concerning the
      hydrogen-bonding partners of their OH groups. However, this strategy requires an
      accurate and efficient means to quantify the influence of the various
      interactions on chemical shielding. Herein the validity of Hartree-Fock and DFT
      calculations of the 13C and 1H NMR chemical shifts of cholesterol and ergosterol
      are compared with one another and with experimental chemical shifts measured in
      solution at 500 MHz. A computational strategy (definition of basis set, simpler
      molecular models for the sterols themselves and their molecular complexes) is
      proposed and compared with experimental data in solution. It is shown in
      particular that the effects of hydrogen bonding with various functional groups
      (water as a hydrogen-bond donor and acceptor, acetone) on NMR chemical shifts in
      CDCl3 solution can be accurately reproduced with this computational approach.

PMID- 15497137
TI  - Enantioselective catalysis with chiral phosphine oxide preligands.

PMID- 15497136
TI  - Understanding sterol-membrane interactions, part II: complete 1H and 13C
      assignments by solid-state NMR spectroscopy and determination of the hydrogen
      bonding partners of cholesterol in a lipid bilayer.
AB  - The complete assignment of cholesterol 1H and 13C NMR resonances in a lipid
      bilayer environment (Lalpha-dimyristoylphosphatidylcholine/cholesterol 2:1) has
      been obtained by a combination of 1D and 2D MAS NMR experiments: 13C spectral
      editing, ge-HSQC, dipolar HETCOR and J-based HETCOR. Specific chemical shift
      variations have been observed for the C1-C6 atoms of cholesterol measured in CCl4
      solution and in the membrane. Based on previous work (F. Jolibois, O. Soubias, V.
      Reat, A. Milon, Chem. Eur. J. 2004, 10, preceding paper in this issue: DOI:
      10.1002/chem.200400245) these variations were attributed to local changes around
      the cholesterol hydroxy group, such as the three major rotameric states of the C3
      O3 bond and different hydrogen bonding partners (water molecules, carboxy and
      phosphodiester groups of phosphatidylcholine). Comparison of the experimental and
      theoretical chemical shifts obtained from quantum-chemistry calculations of
      various transient molecular complexes has allowed the distributions of hydrogen
      bonding partners and hydroxy rotameric states to be determined. This is the first
      time that the probability of hydrogen bonding occurring between cholesterol's
      hydroxy group and phosphatidylcholine's phosphodiester has been determined
      experimentally.

PMID- 15497138
TI  - Zebrafish IRX1b in the embryonic cardiac ventricle.
AB  - The synchronous contraction of the vertebrate heart requires a conduction system.
      While coordinated contraction of the cardiac chambers is observed in zebrafish
      larvae, no histological evidence yet has been found for the existence of a
      cardiac conduction system in this tractable teleost. The homeodomain
      transcription factor gene IRX1 has been shown in the mouse embryo to be a marker
      of cells that give rise to the distinctive cardiac ventricular conduction system.
      Here, I demonstrate that zebrafish IRX1b is expressed in a restricted subset of
      ventricular myocytes within the embryonic zebrafish heart. IRX1b expression
      occurs as the electrical maturation of the heart is taking place, in a location
      analogous to the initial expression domain of mouse IRX1. The gene expression
      pattern of IRX1b is altered in silent heart genetic mutant embryos and in embryos
      treated with the endothelin receptor antagonist bosentan. Furthermore, injection
      of a morpholino oligonucleotide targeted to block IRX1b translation slows the
      heart rate.

PMID- 15497139
TI  - Implication of bax in Xenopus laevis tail regression at metamorphosis.
AB  - Apoptosis is fundamental to normal vertebrate development. A dramatic example of
      postembryonic development involving apoptosis is tail regression during amphibian
      metamorphosis. Earlier studies led us to propose a functional role for the pro
      apoptotic protein Bax in tadpole tail regression. However, its physiological
      relevance has never been analyzed. We have now cloned a cDNA encoding Xenopus
      laevis bax (xlbax) and used in vivo gene transfer in tail muscle to analyze the
      effects of xlbax overexpression. Furthermore, by using an antisense strategy in a
      similar experimental paradigm, xlbax antisense mRNA was shown to block the
      apoptotic effects of xlbax and protect against apoptosis in metamorphosing
      tadpoles. Our results suggest that xlbax is a regulator of muscle fiber death in
      the regressing tail during metamorphosis.

PMID- 15497141
TI  - Tissue inhibitor of metalloproteinase-2 (TIMP-2) expression during cardiac neural
      crest cell migration and its role in proMMP-2 activation.
AB  - Matrix metalloproteinases (MMPs) are important mediators of neural crest (NC)
      cell migration. Here, we examine the distribution of tissue inhibitor of
      metalloproteinase (TIMP) -2 and TIMP-3 and test whether manipulating TIMP levels
      alters chicken cardiac NC cell migration. TIMP-2 mRNA is expressed at stage 11 in
      the neural epithelium and only in migrating cardiac NC cells. TIMP-3 mRNA is
      expressed only in the notochord at stage 8 and later in the outflow tract
      myocardium. Exogenous TIMP-2 increases NC motility in vitro at low concentrations
      but has no effect when concentrations are increased. In vitro, NC cells express
      membrane type-1 matrix metalloproteinase (MT1-MMP) and TIMP-2 and they secrete
      and activate proMMP-2. Antisense TIMP-2 oligonucleotides block proMMP-2
      activation, decrease NC cell migration from explants, and perturb NC
      morphogenesis in ovo. Because TIMP-2 is required for activation of proMMP-2 by
      MT1-MMP, this finding suggests TIMP-2 expression by cardiac NC cells initiates
      proMMP-2 activation important for their migration.

PMID- 15497142
TI  - Origin and evolution of large brains in toothed whales.
AB  - Toothed whales (order Cetacea: suborder Odontoceti) are highly encephalized,
      possessing brains that are significantly larger than expected for their body
      sizes. In particular, the odontocete superfamily Delphinoidea (dolphins,
      porpoises, belugas, and narwhals) comprises numerous species with encephalization
      levels second only to modern humans and greater than all other mammals.
      Odontocetes have also demonstrated behavioral faculties previously only ascribed
      to humans and, to some extent, other great apes. How did the large brains of
      odontocetes evolve? To begin to investigate this question, we quantified and
      averaged estimates of brain and body size for 36 fossil cetacean species using
      computed tomography and analyzed these data along with those for modern
      odontocetes. We provide the first description and statistical tests of the
      pattern of change in brain size relative to body size in cetaceans over 47
      million years. We show that brain size increased significantly in two critical
      phases in the evolution of odontocetes. The first increase occurred with the
      origin of odontocetes from the ancestral group Archaeoceti near the Eocene
      Oligocene boundary and was accompanied by a decrease in body size. The second
      occurred in the origin of Delphinoidea only by 15 million years ago.

PMID- 15497143
TI  - OC29 is preferentially expressed in the presumptive sensory organ region of the
      otocyst.
AB  - The mammalian inner ear derives from the otocyst. Molecular mechanisms underlying
      inner ear development are largely unknown. We have isolated a secreted molecule,
      OC29, from a rat otocyst cDNA library by the signal sequence trap method. OC29
      was revealed to be a rat homologue of human WFIKKN. OC29 is preferentially
      expressed in the developing inner ear and the dorsal neural tube. In the inner
      ear, the expression of OC29 is first detectable at embryonic day 11.5 (E11.5),
      broadly in the dorsolateral region of the otocyst, which gives rise to the
      vestibular organ. At E12.5, the expression of OC29 becomes restricted to the
      presumptive sensory region, mainly to the BMP4-positive presumptive cristae, and
      expression becomes reduced at later stages. These results suggest that OC29 may
      have a role in the early development of the inner ear sensory organ, particularly
      in the formation of the cristae of the semicircular canals.

PMID- 15497144
TI  - Detection of recipient's cells in liver graft using antibodies to mismatched HLA
      class I antigens.
AB  - Engraftment by recipient's (R) cells has been already demonstrated in gender
      mismatched liver grafts using fluorescence in situ hybridization (FISH), with
      contrasting results concerning epithelial cells. Mismatch for human leukocyte
      antigen (HLA) class I (HLA-I) is quite common in patients with orthotopic liver
      transplantation (OLT). We thus aimed to assess whether monoclonal antibodies
      (MoAbs), currently employed in the HLA typing process, could be used to study the
      dynamics of R cells in liver grafts. A total of 50 frozen liver biopsies from 37
      patients receiving a HLA mismatch liver were tested. Biopsies were obtained from
      3 days to more than 360 days after OLT. Frozen sections of graft biopsies were
      stained using an immunoperoxidase technique with the proper MoAbs. In selected
      cases, a double immunofluorescence was also performed. Circulating R blood cells
      and sinusoidal cells were occasionally observed in liver biopsies obtained within
      10 days after OLT and were commonly detected after 1 month. The number of
      sinusoidal cells continued to increase up to 6 months, as shown on serial
      biopsies. On the whole, R blood cells and R sinusoidal cells were detected in 86%
      and 82% of the biopsies, respectively. R hepatocytes and biliary cells were
      detected after 40 and 60 days after OLT, respectively, in 14% (hepatocytes), 8%
      (bile ducts), and 12% (proliferating bile ducts) of the biopsies. R hepatocytes
      presented as single cells or groups of few cells; their number was lower than 1%
      and apparently did not increase with time after OLT. In conclusion, it is
      possible to detect R cells in liver graft using MoAbs to specific mismatched HLA
      I alleles. R sinusoidal cells start to appear after 10 days and are commonly
      observed after 1 month; bile duct cells and hepatocytes appear later and their
      number does not increase with time. Engraftment by R epithelial cells seems to be
      less important than previously reported.

PMID- 15497145
TI  - One-year morbidity after donor right hepatectomy.
AB  - Live donors are becoming an increasingly important source of donor organs in
      liver transplantation; however, long-term functional aspects of recovery from
      donor right hepatectomy are unknown. We analyzed donor outcomes at 1-year follow
      up. We performed a single-center retrospective analysis of 70 right hepatectomy
      donors. Six-week and 1-year postoperative follow-up results were compared to
      preoperative baseline values. Ultrasonography was performed in all donors at 6
      weeks and as clinically indicated. All donors were alive and well at the end of
      the study period. Of 66 right hepatic donors, only 22 (32%) were fully compliant
      with a 1-year follow-up visit. All those not compliant were contacted by phone.
      All complications except 1 (late finding of portal vein thrombosis) occurred in
      the perioperative (90-day) period. The incidence of bile leak was 4.3%,
      incisional hernia 20%, and autologous transfusion 1.0%. There were no aborted
      procedures. In those compliant with full 1-year follow-up, total bilirubin,
      aspartate aminotransferase, and alanine aminotransferase were normal in 97%. A
      total of 5 donors were noted to have persistence of asymptomatic thrombocytopenia
      beyond the perioperative period (90 days). These were investigated with Doppler
      sonography. Sonography was unremarkable in 3 of the 5, while 2 had abnormal
      findings: splenomegaly alone in 1, and splenomegaly with portal vein thrombosis
      in the other. Magnetic resonance angiography was performed in both, and the
      patient with portal vein thrombosis underwent endoscopy, which failed to reveal
      varices. Neither has clinical portal hypertension. Both remain asymptomatic
      albeit with stable thrombocytopenia. In conclusion, the majority of complications
      after donor right hepatectomy occur in the perioperative period. Later findings
      may include asymptomatic thrombocytopenia, with an incidence possibly as high as
      23%, though the significance of this finding remains uncertain. Larger-scale
      studies are needed to confirm the true incidence and clinical significance of
      persistent thrombocytopenia in the donor hepatectomy population. Strategies to
      improve compliance with 1-year follow-up visits need to be developed.

PMID- 15497147
TI  - Safety and efficacy of combined orthotopic liver transplantation and coronary
      artery bypass grafting.
AB  - Advanced coronary artery disease (CAD) is increasingly common in patients
      awaiting orthotopic liver transplantation (OLT). Unfortunately, in patients whose
      coronary artery anatomy is not amenable to angioplasty, coronary artery bypass
      grafting (CABG) alone may precipitate hepatic decompensation. Thus, combined
      liver transplant and coronary artery bypass grafting (CABG-OLT) may be required
      to effectively treat both conditions. Clinical records were analyzed for 5 CABG
      OLT procedures at a single institution. Operative indications, technical details,
      and postoperative course were determined for each patient. Patients undergoing
      CABG-OLT had a mean age of 57.8 years (range, 54-66) and were predominantly male
      (80%). All patients had significant 3-vessel coronary atherosclerotic disease
      with preserved left ventricular function. There were no intraoperative deaths. At
      mean 25 months of follow-up (range, 8.0-25) there was an 80% graft and patient
      survival. Overall average length of stay was 21 days (range, 7-59 days). In
      conclusion, CABG-OLT procedure appears to be safe and effective in the population
      of patients with advanced CAD and liver disease. In this series, patients appear
      to benefit from multidisciplinary preoperative evaluation, coordination between
      cardiac and transplant surgeons, careful graft selection, and use of sapheno
      atrial veno-veno bypass.

PMID- 15497148
TI  - Living donor liver transplant with clinical tolerance, laboratory evidence of
      chimerism, and spontaneous clearance of HBV.
AB  - We present a case of functional and histopathologic tolerance, chimerism, and
      spontaneous clearance of HBV in a patient four years after living donor liver
      transplant (LDLT). A 19-year-old male patient underwent a LDLT for HBV cirrhosis.
      He voluntarily ceased immunosuppression and antiviral therapy after 6 months. He
      is now four years status post transplant without any episodes of rejection or
      clinical manifestation of liver disease. PCR and VNTR were used to show donor
      recipient chimerism and a large degree of genetic similarity between the pair.
      MLC and cytokine elaboration were used to show recipient hyporeactivity towards
      donor antigen. He also has clinical evidence of clearing his HBV without
      continued use of HBIG.

PMID- 15497149
TI  - Liver transplant for the treatment of giant hepatic hemangioma.

PMID- 15497150
TI  - Applicability of histidine-tryptophan-ketoglutarate solution in right lobe adult
      to-adult live donor liver transplantation.
AB  - In a consecutive series of 60 right lobe adult-to-adult live donor liver
      transplantations (ALDLTs), safety and efficacy of the University of Wisconsin
      (UW) and histidine-tryptophan-ketoglutarate (HTK) solution were evaluated. The
      first 30 liver grafts were perfused with UW solution and the subsequent 30 by HTK
      solution. Donor and recipient characteristics of both groups were comparable. All
      liver graft implantations were performed with cross-clamping of the inferior vena
      cava (IVC) and without veno-venous bypass. Main outcome measures were
      posttransplantation liver biochemistry, prothrombin time, and recipient
      morbidity, as well as graft and recipient survival. There were no significant
      differences of the outcome measures between the 2 groups. The low potassium
      content of the HTK solution nonetheless offered logistic advantages. In 25 of the
      30 recipients of the HTK group, portal vein anastomosis was performed with a
      clamp on the donor portal vein while the clamps on the IVC were already released.
      This shortened the period during which the IVC was being cross-clamped. HTK
      solution was as safe and effective as a cold storage solution as UW solution in
      ALDLT. Its low potassium content has advantage of earlier restoration of patency
      of the IVC and thus hemodynamic stability. The cost of using HTK solution was
      also lower.

PMID- 15497151
TI  - Ability to pay and geographical proximity influence access to liver
      transplantation even in a system with universal access.
AB  - Ireland, in common with many countries, has a mixed private and public health
      care system. Concern has been expressed that this system may lead to inequity in
      access to medical treatment. To investigate this concern, all contacts and first
      admissions to the national liver transplant unit were identified between April 1,
      2000, and March 31, 2002. The effects of private health insurance and area of
      residence on the likelihood of receiving a liver transplant were assessed. A
      total of 202 patients were admitted. Forty-three patients from this cohort
      received a liver transplant (21.3%). Of patients with private health insurance,
      17 of 50 (34.0%) were transplanted, compared with 26 of 152 (17.1%) without
      private health insurance (relative risk [RR] = 1.99; 95% CI, 1.18-3.35; P = .01).
      For residents of the Eastern (close to the liver transplant unit), patients with
      private health insurance were no more likely to be transplanted (RR = 0.95; 95%
      CI, 0.35-2.54; P = 1.0), whereas for residents of other areas, patients with
      private insurance were 3 times more likely to receive a transplant than those
      without health insurance (RR = 3.11; 95% CI, 1.59-6.08; P = .001). Patients
      living outside the Eastern region without private health insurance were only half
      as likely as all other patient types combined to receive a transplant (RR = 0.52;
      95% CI, 0.29-0.92; P = .02). In this study the possession of private health
      insurance appeared to increase the chances of receiving a liver transplant.
      Patients without private health insurance living distant from the liver
      transplant unit appeared particularly disadvantaged. In conclusion, these
      findings suggest significant inequity in liver transplant allocation in Ireland
      and deserve further assessment.

PMID- 15497152
TI  - Molecular modeling of green fluorescent protein: structural effects of
      chromophore deprotonation.
AB  - Molecular dynamics (MD) simulations were carried out to study the conformational
      rearrangement induced by deprotonation of the fluorescent chromophore in GFP, as
      well as the associated changes in the hydrogen-bonding network. For both the
      structures with either a neutral or an anionic chromophore, it was found that the
      beta-barrel was stable and rigid, and the conformation of the chromophore was
      consistent with the available x-ray structure. The conformational change in
      Thr203 due to deprotonation was also found to be consistent with the three-state
      isomerization model. Although GFP is highly fluorescent, denatured-GFP is
      nonfluorescent, indicating that the environment of the protein plays an important
      role in its fluorescence behavior. Our MD simulations, which explore the effect
      of the protein shell on the conformation of the chromophore, find the flexibility
      of the central chromophore to be significantly restricted due to the rigid nature
      of the protein shell. The hydrogen-bonding between the chromophore and
      neighboring residues was also shown to contribute to the chromophore rigidity. In
      addition to the MD studies, quantum mechanics/molecular mechanics (QM/MM) ONIOM
      calculations were carried out to investigate the effect of the beta-barrel on the
      internal rotation in the chromophore. Along with providing quantitative values
      for torsional rotation barriers about the bridging bond in the chromophore, the
      ONIOM calculations also validate our MD force field parameters.

PMID- 15497153
TI  - Evidence for the involvement of neurotrophins in muscle transdifferentiation and
      acetylcholine receptor transformation in the esophagus of Myf5(-/-):MyoD(-/-) and
      NT-3(-/-) embryos.
AB  - The primary aim of our study was to determine whether the esophageal innervation
      (i.e., vagal and enteric) and the skeletal muscle-secreted neurotrophins have a
      role in smooth-to-skeletal muscle transdifferentiation and in the muscarinic-to
      nicotinic acetylcholine receptor type transition. To that end, we used
      genetically engineered embryos and immunohistochemistry. We found that, in the
      absence of Myf5 and MyoD, the esophageal muscle cells failed to develop the
      striated phenotype of acetylcholine receptors. In addition, the development of
      vagal and enteric innervation was delayed in Myf5(-/-):MyoD(-/-) and NT-3(-/-)
      mutants, but it was reestablished 2 days before the end of gestation. The smooth
      muscle cells in the esophagus appeared to be a distinct subpopulation of cells
      and their ability to transdifferentiate was based on their competence to express
      neurotrophins and their receptors. Finally, our data suggest a role for NT-3 in
      the esophageal muscle transdifferentiation.

PMID- 15497154
TI  - Autoantibodies against heterogeneous nuclear ribonucleoprotein B1 in CSF of MS
      patients.
AB  - Heterogeneous nuclear ribonucleoproteins (hnRNPs) play an important role as the
      autoantigens in certain autoimmune disorders including neurological diseases such
      as HTLV-1-associated myelopathy/tropical spastic paraparesis and paraneoplastic
      neurological syndromes. To clarify their implication in multiple sclerosis (MS),
      we assayed antibodies (Abs) against hnRNP A and B proteins in sera and
      cerebrospinal fluid (CSF) of MS patients and compared the results with 25
      patients with other neurological diseases (ONDs). Using recombinant hnRNP A1, A2,
      and B1 proteins and Western blotting for the assay, we found Abs against hnRNP B1
      in CSF from 32 of 35 MS patients (91.4%) but not in any sera or CSF of the 25 OND
      patients. Most notably, no Abs against hnRNP B1 were found in sera of all 22 MS
      patients examined. Although Abs against hnRNP A1 and A2 were concomitantly found
      in CSF reacting with B1, their incidence and immunoreactivity were lower or
      weaker than those of anti-hnRNP B1 Abs. There was no correlation between the
      reactivity of CSF with hnRNP B1 and CSF parameters-such as the number of the
      cells and the IgG level-or clinical parameters-such as duration of illness and
      disease activity. The selective generation of Abs against hnRNP B1 in CSF was
      shown to be highly specific for MS, which makes them a disease marker.

PMID- 15497155
TI  - C-peptide prevents nociceptive sensory neuropathy in type 1 diabetes.
AB  - We examined the effects of C-peptide replacement on unmyelinated fiber function
      in the hind paw, sural nerve C-fiber morphometry, sciatic nerve neurotrophins,
      and the expression of neurotrophic receptors and content of neuropeptides in
      dorsal root ganglia in type 1 diabetic BB/Wor-rats. C-peptide replacement from
      onset of diabetes had no effect on hyperglycemia, but it significantly prevented
      progressive thermal hyperalgesia and prevented C-fiber atrophy, degeneration, and
      loss. These findings were associated with preventive effects on impaired
      availability of nerve growth factor and neurotrophin 3 in the sciatic nerve and
      significant prevention of perturbed expression of insulin, insulin growth factor
      1, nerve growth factor, and neurotrophin 3 receptors in dorsal root ganglion
      cells. These beneficial effects translated into prevention of the decreased
      content of dorsal root ganglia nociceptive peptides such as substance P and
      calcitonin gene-related peptide. From these findings we conclude that replacement
      of insulinomimetic C-peptide prevents abnormalities of neurotrophins, their
      receptors, and nociceptive neuropeptides in type 1 BB/Wor-rats, resulting in the
      prevention of C-fiber pathology and nociceptive sensory nerve dysfunction. The
      data indicate that perturbed insulin/C-peptide action plays an important
      pathogenetic role in nociceptive sensory neuropathy and that C-peptide
      replacement may be of benefit in treating painful diabetic neuropathy in insulin
      deficient diabetic conditions.

PMID- 15497156
TI  - Preoperative evaluation of biliary anatomy in adult live liver donors with
      volumetric mangafodipir trisodium enhanced magnetic resonance cholangiography.
AB  - Accurate preoperative depiction of biliary anatomy is not always adequately
      accomplished by imaging techniques in living donor liver transplantation (LDLT).
      We present the results of a prospective study designed to evaluate the ability of
      mangafodipir trisodium (Mn-DPDP)-enhanced magnetic resonance (MR) cholangiography
      (MRC) for this purpose in a series of 25 adult living liver donors (LLDs). We
      also analyze if a simple or a more complex surgical procedure can be
      preoperatively suggested for biliary reconstruction in the recipients. Findings
      on MRC were compared with operative cholangiography (OC). A conventional
      distribution with a right hepatic duct (RHD) longer than 1 cm anticipated a
      simple procedure (duct-to-duct anastomosis or hepaticojejunostomy [HJ]). A
      shorter RHD or any variant were predictors of a more complex surgery (bench
      ductoplasty or multiple anastomoses). Agreement between MRC and OC in assessing
      the biliary anatomy was measured using the kappa statistic, and differences
      between the kind of surgery predicted at MRC and the biliary anastomosis
      performed were evaluated with Fisher's exact test. Normal variants were present
      in 16 / 25 donors (64%). MRC was accurate in depicting the pattern of bile duct
      distribution observed at OC in 22 / 25 (88%) donors (kappa = .831), and correctly
      predicted the complexity of biliary anastomosis in the recipient in 22 / 25 (88%)
      donors. No significant differences were observed between complexity of biliary
      surgery proposed at MRC and the final surgery performed (P = .002). In
      conclusion, Mn-DPDP-enhanced MRC is highly accurate in depicting the biliary duct
      anatomy and can be used preoperatively for surgical planning in LDLT.

PMID- 15497157
TI  - Simplified standardized technique for living donor liver transplantation using
      left liver graft plus caudate lobe.
AB  - Concomitant resection of the caudate lobe (CL) would increase the liver mass in
      the left liver graft. We tried to define a simplified standardized technique for
      adult living donor liver transplantation using the extended left lobe (ELL) plus
      CL (ELLC) through a prospective study of 27 consecutive ELLC graft cases in 2003.
      Donor CL was dissected toward the 10 o'clock direction and transected at the
      midpoint between the trunks of the right hepatic vein (RHV) and the middle
      hepatic vein (MHV). This orthodox transection was performed in 18 cases, but the
      transection plane was moved left in 9 cases. Compared with conventional left
      liver implantation, there was no additional reconstruction except for single
      revascularization of the largest short hepatic vein of the CL (V1) in 21 cases.
      On 1-week computed tomography (CT) images, the perfusion states of the CL portion
      were good in 15 cases, fair in 7 cases, and poor in 5 cases. Regeneration of the
      CL portion during the 1st week was +43%, +18%, and -10% in the good, fair, and
      poor perfusion groups, respectively. There were positive correlations among the
      perfusion state of the CL, the location of the CL transection plane, and the
      width of the CL portion that was attached to the left liver graft. CL
      implantation resulted in a mean gain of graft mass by 5.9% in the left liver at
      the time of operation and by 3.9% after 1 week. There were no donor
      complications, and 25 recipients (93%) survive to date. In conclusion, this
      simplified standardized technique was feasible for most of the living donor
      livers and required only 1 additional reconstruction of the V1.

PMID- 15497158
TI  - Liver transplantation outcomes for early-stage hepatocellular carcinoma: results
      of a multicenter study.
AB  - The incidence of hepatocellular carcinoma (HCC), a frequent and incurable
      complication of cirrhosis, continues to rise. Orthotopic liver transplantation
      (OLT) has been proposed as a treatment for unresectable, intrahepatic HCC limited
      in extent to the Milan criteria adopted by the United Network of Organ Sharing
      (UNOS) in 1998. More recently, somewhat less restrictive University of
      California, San Francisco (UCSF)10, criteria were proposed. To examine the long
      term outcomes of OLT for HCC patients and to assess the UNOS policy of assigning
      weighted allocation points to patients with HCC, we retrospectively analyzed 144
      patients (113 after 1998) with HCC who underwent OLT over an 11-year period at 3
      institutions from UNOS Region 1. We compared their outcomes with 525 patients
      (272 after 1998) who underwent OLT for nonmalignant liver disease. The 1- and 5
      year survival rates were 80.3% and 46.7%, respectively, for patients with HCC and
      81.5% and 70.6%, respectively, for patients without HCC (P = .020). However,
      there was no difference in survival between HCC and non-HCC patients after
      implementation of disease-specific allocation for HCC in 1998. A higher
      proportion of the HCC cohort was older and male and had chronic HCV infection and
      alcoholic liver disease. In univariate analysis, having alpha-fetoprotein (AFP)
      levels of 10 ng/mL or less and meeting clinical and pathologic UCSF criteria were
      each significant predictors of improved survival (P = .005, P = .02, and P = .03,
      respectively). AFP greater than 10 ng/mL and exceeding pathologic UCSF criteria
      were also significant predictors of recurrence (P = .003 and P = .02,
      respectively). In conclusion, taken together, our data suggest that OLT is an
      acceptable option for patients with early HCC and that UCSF criteria predict
      outcome better than Milan or UNOS criteria. Regardless of which criteria are
      adopted to define eligibility, strict adherence to the criteria is important to
      achieve acceptable outcomes.

PMID- 15497159
TI  - Posttransplant survival in pediatric fulminant hepatic failure: the SPLIT
      experience.
AB  - Pediatric patients with fulminant hepatic failure (FHF) tend to be the sickest
      and have the most urgent need for a liver transplant. The purpose of this
      analysis was to identify factors associated with posttransplant survival in this
      subset of patients. Data on all FHF patients registered in the Studies of
      Pediatric Liver Transplantation (SPLIT) registry from 1995 to 2002 were analyzed.
      Demographics such as age, gender, race, weight, and etiology of liver disease
      were recorded. Pretransplant degree of encephalopathy; intubation; dialysis;
      laboratory parameters such as serum bilirubin and international normalized ratio
      of coagulopathy (INR); and type of graft: cadaveric whole, cadaveric technical
      variant, or living donor were analyzed to determine effects on patient survival.
      Overall, FHF accounted for 12.9% (141 / 1,092) of primary transplants performed
      between 1995 and 2002. The etiology of liver disease was unknown in the vast
      majority of children (126 / 141; 89.4%). Mortality while on the waiting list for
      FHF children is significantly higher than for children with other liver disease
      (P < .0001). Six-month survival posttransplant for patients with FHF (74.5%) is
      significantly lower (P < .0001) than those with chronic liver disease (88.9%). A
      multivariate model demonstrates that the highest risk group includes those
      children with grade 4 encephalopathy (P < .0001), infants less than 1 year of age
      (P = .018), and children requiring dialysis prior to transplantation (P = .002).
      Pretransplant bilirubin and INR were not significant predictors of posttransplant
      survival after controlling for the other significant factors. Living donor and
      split / reduced grafts did not have a significantly increased risk of
      posttransplant death compared to whole grafts. In conclusion, despite advances in
      the surgical techniques and changes in organ allocation, pediatric patients with
      FHF continue to have a high pretransplant mortality and less successful
      posttransplant survival compared to children with chronic liver disease.

PMID- 15497160
TI  - Risk factors for renal dysfunction in the postoperative course of liver
      transplant.
AB  - Renal dysfunction (RD) is a frequent complication after orthotopic liver
      transplantation (OLT), and it has an unfavorable effect on the prognosis of OLT
      patients. The purpose of our study was to identify possible risk factors for RD
      and its impact on survival. The possible relations of pre-, peri-, and
      postoperative variables to early-onset renal dysfunction (ED) (within the 1st 3
      months), late-onset renal dysfunction (LD) (between 3 and 6 months), and chronic
      renal dysfunction (CRD) (beyond 6 months) was analyzed. We studied 245 liver
      transplants in 241 patients. RD was found in 64.1% of these patients, and 69% of
      the patients with RD recovered. LD was found in 16.7% of the transplant patients.
      In the multivariate analysis, baseline serum creatinine, perioperative volume of
      transfused bank-red blood cells, Acute Physiology and Chronic Health Evaluation
      (APACHE) II score at intensive care unit (ICU) admission, and infection were
      associated with the development of RD. Overall mortality was 27.8% and for the RD
      group, it was 33.5%. LD, but not ED, was related to lower survival (together with
      graft dysfunction and APACHE II score at ICU admission). In conclusion, ED is
      frequent alter OLT and is related to preexisting RD, the volume of transfused
      bank--red blood cells during surgery, higher APACHE II score at ICU admission,
      and infection. In general, the prognosis for ED is good, in contrast with that of
      LD, which is associated with diminished survival.

PMID- 15497161
TI  - Hepatic tissue engineering for adjunct and temporary liver support: critical
      technologies.
AB  - The severe donor liver shortage, high cost, and complexity of orthotopic liver
      transplantation have prompted the search for alternative treatment strategies for
      end-stage liver disease, which would require less donor material, be cheaper, and
      less invasive. Hepatic tissue engineering encompasses several approaches to
      develop adjunct internal liver support methods, such as hepatocyte
      transplantation and implantable hepatocyte-based devices, as well as temporary
      extracorporeal liver support techniques, such as bioartificial liver assist
      devices. Many tissue engineered liver support systems have passed the "proof of
      principle" test in preclinical and clinical studies; however, they have not yet
      been found sufficiently reliably effective for routine clinical use. In this
      review we describe, from an engineering perspective, the progress and remaining
      challenges that must be resolved in order to develop the next generation of
      implantable and extracorporeal devices for adjunct or temporary liver assist.

PMID- 15497162
TI  - Survival of cirrhotic patients with early hepatocellular carcinoma treated by
      percutaneous ethanol injection or liver transplantation.
AB  - For "early" hepatocellular carcinoma (HCC), surgery, orthotopic liver
      transplantation (OLT) and percutaneous ethanol injection (PEI) improve the
      natural history of the disease. We performed a retrospective study to evaluate
      the outcome of patients with cirrhosis and early HCC treated by PEI (n = 417) or
      OLT (n = 172). Overall, 589 patients with cirrhosis were studied. The proportion
      of patients in Child-Turcotte-Pugh (CTP) classes A, B, and C was 52.5%, 33.6%,
      and 13.9%, respectively. Most patients (78.9%) had solitary HCC. Overall 5-year
      and 10-year cumulative survival rates were 36.1% and 15.5% after PEI, and 66.3%
      and 49.1% after OLT, respectively (P < .0001). Overall 5-year and 10-year
      cumulative tumor-free survival rates were 25.3% and 18.0% after PEI, and 84.6%
      and 82.2% after OLT, respectively (P < .0001). When patients were sorted
      according to the severity of cirrhosis, mean survival times in PEI and OLT
      patients were 67 and 80 months in CTP class A (P = .05), 38 and 90 months in
      class B (P < .0001), and 31 and 95 months in class C (P = .0004). Similarly, mean
      tumor-free survival times in the 2 series of patients were 49 and 98 months in
      CTP class A (P < .0001), 39 and 121 months in class B (P < .0001), and 35 and 139
      months in class C (P < .0001). In conclusion, this study challenges the
      therapeutic efficacy of PEI for patients with cirrhosis and early HCC, when
      compared to OLT: the proportion of both long-term survivors and tumor-free
      survivors was increased by OLT over PEI. The benefit of OLT extends to all
      patients, regardless of the degree of liver impairment.

PMID- 15497163
TI  - Outcomes in liver transplant recipients with hepatitis B virus: resistance and
      recurrence patterns from a large transplant center over the last decade.
AB  - Hepatitis B virus (HBV) recurrence following liver transplantation (LTx) has been
      controllable primarily with the use of hepatitis B immune globulin (HBIg) and
      lamivudine (LAM). However, HBV resistance to LAM and/or HBIg has become an
      increasing problem prompting the use of newer antiviral agents. The purpose of
      our study was to investigate the association between therapy, HBV breakthrough,
      and allograft / patient survival in HBV-positive liver transplant recipients. We
      performed a retrospective review of the medical records of patients that were
      transplanted for HBV from June 1994 to May 2003. A total of 92 patients, positive
      for either hepatitis B surface antigen (HBsAg) or HBV deoxyribonucleic acid (DNA)
      pretransplant, received LAM monotherapy or HBIg (6 months) plus LAM therapy post
      liver transplant. HBV breakthrough post-LTx was noted in 14 patients. All
      patients had detectable HBV DNA prior to liver transplantation; none of the
      patients that were HBV DNA negative prior to transplant had detectable HBV DNA
      posttransplant. Of these 14, 9 patients (64%) were switched from LAM to adefovir
      dipivoxil (ADF) and 5 patients (36%) to tenofovir disoproxil fumarate (TNV). In
      conclusion, pre-LTx HBV viremia should be considered in planning post-LTx
      prophylaxis. Trials to evaluate oral antiviral agents in combination with or
      without HBIg therapy are needed.

PMID- 15497164
TI  - In vivo performance of the Nitinol shape-memory stapes prosthesis during hearing
      restoration surgery in otosclerosis: a first report.
AB  - The limitations of manual prosthesis crimping in hearing restoration surgery for
      otosclerosis are thought to have a key role in the occurrence of incomplete
      postoperative elimination of conductive hearing loss and postoperative
      recurrences of conductive hearing loss. To eliminate manual crimping, the self
      crimping, shape-memory alloy Nitinol stapes piston was introduced in nine
      otosclerosis patients. The results were compared with those in a database of
      surgeries performed with conventional titanium pistons. The effects of the self
      crimping Nitinol prosthesis on the postoperative elimination of conductive
      hearing loss and its postoperative variations were investigated. The variations
      of postoperative residual conductive hearing loss were significantly smaller and
      the extent of conductive hearing-loss elimination greater in the Nitinol group.
      The mean postoperative residual conductive hearing loss was smaller in the
      Nitinol group. The postoperative stability of conductive hearing loss elimination
      was similar in both patient groups. Preliminary results suggest that the self
      crimping shape-memory alloy Nitinol stapes piston overcomes the drawbacks of
      manual crimping in hearing restoration surgery for otosclerosis.

PMID- 15497165
TI  - Zirconia to Ti-6Al-4V braze joint for implantable biomedical device.
AB  - A strong, hermetic, reliable, and biocompatible ceramic-to-metal seal is
      essential for many implantable medical devices. Yttria-stabilized tetragonal
      zirconia polycrystals (Y-TZPs) and a titanium alloy Ti-6Al-4V were selected as
      the ceramic and metal components of the seal because both materials have
      excellent mechanical properties and favorable biocompatibility. A brazing method
      using titanium nickel (TiNi)-clad braze filler material is presented to bond the
      components together forming a seal. Laboratory tests show that the ceramic-to
      metal seal is hermetic, strong, and resistant to electrochemical corrosion.
      Twenty-eight microstimulators utilizing the ceramic-to-metal seals were implanted
      in seven sheep to stimulate the hypoglossal nerve. When the tissue was evaluated
      by gross inspection at necropsy and examined histologically by a pathologist,
      there were no signs of local hemorrhage, infection, or hypoglossal nerve tissue
      damage.

PMID- 15497166
TI  - Subsurface microstructure of metal-on-metal hip joints and its relationship to
      wear particle generation.
AB  - To control and minimize wear of metal-on-metal hip joints it is essential to
      understand the mechanisms of debris generation. In vivo, mainly nanosize globular
      and needle-shaped particles are found. These can neither stem from the action of
      abrasion nor from tribochemical reactions. In this study the acting wear
      mechanisms have been first identified on the surface by means of scanning
      electron microscopy (SEM). Afterwards, the microstructures of the subsurface
      regions of explants have been investigated using a transmission electron
      microscope (TEM). Observation of the subsurface gave additional insight about the
      microstructural changes of cobalt-base alloys subjected to wear. At some distance
      from the surface, a network of stacking faults and hexagonal epsilon-martensite
      was found strengthening the bulk material. This microstructure changed into a
      nanocrystalline type moving closer towards the surface. A comparison of in vivo
      debris size and grain size of the surface suggests that the globular wear
      particles result from torn off nanocrystals, while the needle shaped particles
      are generated by fractured epsilon-martensite. Identified cracks, propagating
      through the nanocrystalline layer, further support these findings. Thus, it is
      suggested that the dominating mechanism of particle generation for metal-on-metal
      joints is surface fatigue within a nanocrystalline surface layer.

PMID- 15497167
TI  - Pulpal temperature rise during light-activated bleaching.
AB  - The purpose of this study was to measure intrapulpal temperature rise induced by
      two kinds of bleaching gels when the tooth was exposed to a variety of light
      curing units and a diode laser in vitro. The root portions of 80 extracted intact
      human maxillary central incisors were sectioned with a carborundum disk
      approximately 2 mm below the cementoenamel junction perpendicular to the long
      axis of the teeth. Two bleaching agents containing heat-enhancing colorant was
      applied to the labial surface. Light-curing units used were a conventional
      halogen (40 s), a high-intensity halogen (30 s), a light-emitting diode unit (40
      s), and a diode laser (15 s). The temperature rise was measured in the pulpal
      chamber with a J-type thermocouple wire that was connected to a data logger. Ten
      specimens were used for each system and bleaching-agent combination. Differences
      between the starting temperature and highest temperature reading were taken and
      the calculated temperature changes were averaged to determine the mean value in
      temperature rise. Temperature rise values were compared using two-way analysis of
      variance (ANOVA) at a preset alpha of 0.05. Temperature rise varied significantly
      depending on curing unit and diode laser used. The diode laser induced
      significantly higher temperature increases than any other curing unit (11.7
      degrees C). The light-emitting diode unit produced the lowest temperature changes
      (6.0 degrees C); however, there were no statistically significant differences
      among the curing units and there were no statistically significant differences
      between bleaching agents. Light activation of bleaching materials with diode
      laser caused higher temperature changes as compared to other curing units and the
      temperature rise detected was viewed as critical for pulpal health.

PMID- 15497168
TI  - Elemental distributions and microtensile bond strength of the adhesive interface
      to normal and caries-affected dentin.
AB  - The aim of this study was to evaluate the microtensile bond strength (microTBS)
      and the elemental contents of the adhesive interface created to normal versus
      caries-affected dentin. Extracted human molars with coronal carious lesions were
      used in this study. A self-etching primer/adhesive system (Clearfil Protect Bond)
      was applied to flat dentin surfaces with normal and caries-affected dentin
      according to the manufacturer's instructions. After 24 h water storage, the
      bonded specimens were cross-sectioned and subjected to a microTBS test and
      electron probe microanalysis for the elemental distributions [calcium (Ca),
      phosphorus (P), magnesium (Mg), and nitrogen (N)] of the resin-dentin interface
      after gold sputter-coating. The microTBS to caries-affected dentin was lower than
      that of normal dentin. The demineralized zone of the caries-affected dentin-resin
      interface was thicker than that of normal dentin (approximately 3 microm thick in
      normal dentin; 8 microm thick in caries-affected dentin), and Ca and P in both
      types of dentin gradually increased from the interface to the underlying dentin.
      The caries-affected dentin had lost most of its Mg content. The distributions of
      the minerals, Ca, P, and Mg, at the adhesive interface to caries-affected dentin
      were different from normal dentin. Moreover, a N peak, which was considered to be
      the collagen-rich zone resulting from incomplete resin infiltration of exposed
      collagen, was observed to be thicker within the demineralized zone of caries
      affected dentin compared with normal dentin.

PMID- 15497169
TI  - New strategy for the synthesis of 3',5'-bifunctionalized oligonucleotide
      conjugates through sequential formation of chemoselective oxime bonds.
AB  - A convenient strategy for the synthesis of bifunctionalized oligonucleotide
      conjugates bearing two different reporters at the 3' and 5' ends of the
      oligonucleotide is presented. The method involves the preparation of
      oligonucleotides bearing an aldehyde and/or aminooxy functionality at each end,
      followed by reaction to form oxime bonds with appropriately functionalized
      reporters. The conjugation reactions are carried out under mild aqueous
      conditions with good reaction yield.

PMID- 15497171
TI  - On a policy of transferring public patients to private practice.
AB  - We consider an economy where public hospitals are capacity-constrained, and we
      analyse the willingness of health authorities to reach agreements with private
      hospitals to have some of their patients treated there. When physicians are dual
      suppliers, we show that a problem of cream-skimming arises and reduces the
      incentives of the health authority to undertake such a policy. We argue that the
      more dispersed are the severities of the patients, the greater the reduction in
      the incentives will be. We also show that, despite the patient selection problem,
      when the policy is implemented it is often the case that health authorities
      decide a more intensive transfer of patients to private practice.

PMID- 15497174
TI  - Food and Nutrition: Focus on the Molecular Level.
AB  - No Abstract.

PMID- 15497172
TI  - Azithromycin for acute lower respiratory tract infections.
AB  - BACKGROUND: The spectrum of acute lower respiratory tract infection ranges from
      acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia.
      Annually approximately five million people die of acute respiratory tract
      infections. Among these, pneumonia represents the most frequent cause of
      mortality, hospitalization and medical consultation. Azithromycin is a new
      macrolide antibiotic, structurally modified from erythromycin and is noted for
      its activity against some gram-negative organisms associated with respiratory
      tract infections, particularly Haemophilus influenzae (H. influenzae).
      OBJECTIVES: To compare the effectiveness of azithromycin to amoxycillin or
      amoxycillin/clavulanic acid (amoxyclav) in the treatment of LRTI, in terms of
      clinical failure, incidence of adverse events and microbial eradication. SEARCH
      STRATEGY: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library Issue 4, 2003), MEDLINE (January 1966 to January
      Week 3, 2004), and EMBASE (January 1988 to 2003). SELECTION CRITERIA: Randomised
      and quasi-randomised controlled trials, which compared azithromycin to
      amoxycillin or amoxycillin/clavulanic acid in patients with clinical evidence of
      acute LRTI: acute bronchitis, pneumonia, and acute exacerbation of chronic
      bronchitis were studied. DATA COLLECTION AND ANALYSIS: The criteria for assessing
      study quality were generation of allocation sequence, concealment of treatment
      allocation, blinding, and completeness of the trial. All types of acute lower
      respiratory tract infections were initially pooled in the meta-analyses. Funnel
      plot was used to examine publication bias. The heterogeneity of results was
      investigated by the forest plot and Chi-square test. Index of I(2) was also used
      to measure inconsistency results among trials. Subgroup analysis was conducted
      for age, types of respiratory tract infection and types of antibiotic in control
      groups. Sensitivity analysis was conducted under the condition of trial size and
      concealment of treatment allocation. MAIN RESULTS: Fourteen trials with 2,521
      enrolled patients used 2,416 patients in the analysis. A total of 1,350 patients
      received azithromycin and 1,066 received amoxicillin or amoxicillin-clavulanic
      acid. The pooled analysis of all trials showed that there was no significant
      difference in the incidence of clinical failure on about day 10 to 14 after
      therapy started between the two groups (relative risk (RR) (random effects) 0.96;
      95% CI 0.58 to 1.57). Sensitivity analysis showed that a reduction of clinical
      failure in azithromycin-treated patients (RR 0.52; 95% CI 0.24 to 1.12) in three
      adequately concealed studies, compared to RR 1.14 (95% CI 0.62 to 2.08) in eleven
      studies with inadequate concealment. Eleven trials reported the incidence of
      microbial eradication and there was no significant difference between the two
      groups (RR 0.98; 95% CI 0.91 to 1.07). The reduction of adverse events in
      azithromycin group was RR 0.75 (95% CI 0.56 to 1.00). REVIEWERS' CONCLUSIONS:
      There is unclear evidence that azithromycin is superior to amoxicillin or
      amoxicillin-clavulanic acid in treating acute LRTI. Future trials with high
      methodological quality are needed.

PMID- 15497175
TI  - The discovery of alapyridaine, a new multimodal flavor enhancer.

PMID- 15497176
TI  - Vibrational circular dichroism: chiroptical analysis of biomolecules.

PMID- 15497177
TI  - Effects of thermal food processing on the chemical structure and toxicity of
      fumonisin mycotoxins.
AB  - Fumonisins are Fusarium mycotoxins that occur in corn and corn-based foods. They
      are toxic to animals and at least one analogue, fumonisin B1, is carcinogenic to
      rodents. Their effect on human health is unclear, however, fumonisins are
      considered to be risk factors for cancer and possibly neural tube defects in some
      heavily exposed populations. It is therefore important to minimize exposures in
      these populations. Cleaning corn to remove damaged or moldy kernels reduces
      fumonisins in foods while milling increases their concentration in some and
      reduces their concentration in other products. Fumonisins are water-soluble and
      nixtamalization (cooking in alkaline water) lowers the fumonisin content of food
      products if the cooking liquid is discarded. Baking, frying, and extrusion
      cooking of corn at high temperatures ( > or = 190 degrees C) also reduces
      fumonisin concentrations in foods, with the amount of reduction achieved
      depending on cooking time, temperature, recipe, and other factors. However, the
      chemical fate of fumonisins in baked, fried, and extruded foods is not well
      understood and it is not known if the reduced concentrations result from thermal
      decomposition of fumonisins or from their binding to proteins, sugars or other
      compounds in food matrices. These possibilities might or might not be beneficial
      depending upon the bioavailability and inherent toxicity of decomposition
      products or the degree to which bound fumonisins are released in the
      gastrointestinal tract. In this review the affects of cooking and processing on
      the concentration and chemical structure of fumonisins as well as the
      toxicological consequences of known and likely fumonisin reaction products are
      discussed.

PMID- 15497178
TI  - Systematic studies of structure and physiological activity of alapyridaine. A
      novel food-born taste enhancer.
AB  - By application of taste dilution analysis (+)-(S)-1-(1-carboxyethyl)-5-hydroxy-2
      (hydroxymethyl)-pyridinium inner salt was recently successfully identified as a
      multimodal taste enhancer in beef bouillon. While being taste-less on its own,
      this so-called alapyridaine was found to intensify the human perception of sweet,
      salty, and umami taste. To gain information on the molecular requirements of this
      novel class of taste enhancer, a range of structurally related pyridinium
      betaines were synthesized, purified, and their physiological activities
      sensorially evaluated. Removal or modification of the hydroxyl and the
      hydroxymethyl group, respectively, induced a loss in bioactivity, thus indicating
      the 2-(hydroxymethyl)-5-hydroxypyridinium moiety as an essential structural
      element for taste enhancement. Regarding the amino substituent, neither the
      prolongation or removal of the alkyl chain or the carboxy function in the 1-(1
      carboxy-2-ethyl)-moiety, nor the incorporation of an additional carboxy function
      led to any active derivative, thus demonstrating that also the structure of the
      nitrogen substituent is rather conserved for taste enhancement. But substitution
      of the methyl group by a benzyl group yielded a compound showing similar taste
      enhancing activities as found for alapyridaine. Interestingly, additional
      insertion of glycine between the 1-(1-carboxy-2-phenylethyl)-moiety and the
      pyridinium ring resulted in a compound eliciting comparable taste enhancing
      effects as shown for the compound lacking the glycine spacer. In contrast to
      these multimodal taste enhancers, substitution of the alanine moiety in
      alapyridaine by an arginine moiety revealed an one-dimensional taste enhancer
      exclusively increasing the human sensitivity for salty taste.

PMID- 15497179
TI  - Sensitive in vitro test systems to determine androgenic/antiandrogenic activity.
AB  - We report on the establishment of one transgenic and two endogenous reporter gene
      assays to determine androgenic/antiandrogenic activity. A transient
      transactivation assay was developed in COS-7 African green monkey kidney cells.
      Three plasmids were co-transfected by electroporation: the human androgen
      receptor expression vector pSG5AR, the reporter gene vector pMamneoLuc,
      expressing luciferase under the control of the mouse mammary tumor virus (MMTV)
      promotor containing 4 hormone responsive elements (HREs), and the control plasmid
      pSVbeta. Transcriptional activation was measured by luciferase-mediated
      chemoluminescence. In T47D human breast cancer cells two endogenous reporter gene
      systems were established: one based on the androgen-induced expression of
      prostate-specific antigen (PSA), the other based on the androgen-repressed
      expression of testosterone repressed message 2 (TRPM-2). PSA protein was measured
      by enzyme-linked immunosorbent assay (ELISA), TRPM-2 m-RNA by reverse
      transcriptase polymerase chain reaction (RT-PCR). All three test systems were
      validated using the physiological androgen dihydrotestosterone (DHT) as agonist
      and the established antiandrogens hydroxyflutamide and p,p'
      dichlorodiphenylethene (p,p'-DDE) as antagonists. The PSA assay was the most
      sensitive test system with an EC50 of 0.7 nM for DHT-induced response. The
      transient transactivation assay in COS-7 cells was less sensitive with an EC50 of
      9.7 nM DHT. In the PSA assay hydroxyflutamide was a more potent antagonist (IC30
      = 0.02 microM) than p,p'-DDE (IC30 = 0.9 microM). In the transient
      transactivation assay in COS-7 cells, both compounds elicited about 30% of the
      agonistic response induced by 100 nM DHT, thus showing partial agonistic
      properties. In summary, three highly sensitive and complementary in vitro test
      systems, together achieving enhanced specificity for detection and assessment of
      androgenic/antiandrogenic activity have been established and validated.

PMID- 15497180
TI  - Heterocyclic amines in some Swedish cooked foods industrially prepared or from
      fast food outlets and restaurants.
AB  - Accurate assessment of human intake of mutagenic/carcinogenic heterocyclic amines
      (HAs) is necessary for epidemiological studies and future risk assessment. Using
      questionnaires, the frequency of consumption of specific dishes can be obtained
      at an individual level and linked to analyzed concentrations of different
      compounds in corresponding dishes. Some typical Swedish cooked meat dishes,
      hamburgers and kebab, industrially prepared or from fast food outlets and
      restaurants, were analyzed regarding their content of 11 different HAs. The
      amount of each of these compounds was below 0.1 ng/g cooked weight in most of the
      industrially prepared products. The total amount of HAs was highest in the kebab
      samples. The intake of HAs from 200 g of the dishes was estimated to range from
      not detectable levels to 0.6 microg. The results of the present study indicate
      that the content of HAs in a specific dish may vary with origin, and that the
      concentrations of HAs in commercial fried meat products are generally low,
      although some of these food items may contain elevated amounts.

PMID- 15497181
TI  - Levels of mycotoxins and sample cytotoxicity of selected organic and conventional
      grain-based products purchased from Finnish and Italian markets.
AB  - The contamination levels of 16 different Fusarium- and Aspergillus-mycotoxins
      were chemically determined from randomly selected organic and conventional grain
      based products purchased from Finnish and Italian markets. The cytotoxicity of
      the samples was analyzed with an in vitro test using feline fetal lung cells.
      Overall, the concentrations of the mycotoxins studied were low in all of the
      samples. Enniatins B and B1 as well as deoxynivalenol were the most predominant
      mycotoxins in the samples, being present in 97%, 97%, and 90% of the samples,
      respectively. The geographical origin or the agricultural practice had no
      influence on the mycotoxin concentrations of the samples. The babyfoods included
      in the samples had significantly lower concentrations of mycotoxins than the
      other products with a mean total mycotoxin content of 47 microg/kg compared with
      99 microg/kg for the other kinds of food. All the samples evoked toxicity in the
      in vitro test, but no correlation between cytotoxicity and the mycotoxin
      concentrations was observed.

PMID- 15497182
TI  - Antioxidant activity of plant extracts on the inhibition of citral off-odor
      formation.
AB  - Grape seed, pomegranate seed, green tea, and black tea extracts were used to
      inhibit the off-odor from citral degradation. A 0.1 M citrate buffer (pH 3),
      containing 100 ppm citral and 200 ppm gallic acid equivalent plant extract, was
      incubated at 40 degrees C. The reaction mixtures were analyzed by high
      performance liquid chromatography (HPLC) at days 0, 6, 10, 13, and 16 to monitor
      degradation of citral and formation of alpha, p-dimethylstyrene, p-cymene-8-ol,
      and p-methylacetophenone. The addition of plant phenolic extracts could not
      inhibit citral degradation, however, all four plant extracts significantly
      inhibited p-methylacetophenone formation. The samples, with the addition of plant
      extracts, exhibited higher concentrations of alpha, p-dimethylstyrene and p
      cymene-8-ol than the control. This is presumed to be due to the oxygen-scavenging
      effect of plant extracts blocking the pathway from p-cymene-8-ol to p
      methylacetophenone. Our results suggest that these plant extracts act as general
      antioxidants inhibiting the generation ofp-methylacetophenone regardless of the
      types of water-soluble phenolic compounds existing in the plant extracts.

PMID- 15497183
TI  - The substitution pattern of anthocyanidins affects different cellular signaling
      cascades regulating cell proliferation.
AB  - The aglycons of the most abundant anthocyanins in food, cyanidin (cy) and
      delphinidin (del), represent potent inhibitors of the epidermal growth factor
      receptor (EGFR). Structure-activity studies show that the presence of vicinal
      hydroxy substituents at the phenyl ring at the 2-position (B-ring) is crucial for
      target interaction. The presence of a single hydroxy group or introduction of
      methoxy substituents at the B-ring results in a substantial loss of inhibitory
      properties. However, biological activity is not exclusively limited to compounds
      bearing vicinal hydroxy groups. A contradictory structure-activity relationship
      is observed for the inhibition of cAMP-specific phosphodiesterases (PDEs). Of the
      anthocyanidins tested, malvidin, bearing methoxy substituents in the 3'- and 5'
      positions, most effectively inhibited cAMP hydrolysis. The absence of methoxy
      groups and/or replacement by hydroxy substituents was found to strongly diminish
      PDE-inhibitory properties. We found that either effective EGFR inhibition or
      effective PDE inhibition is required to achieve a shut-down of the central
      mitogen-activated protein kinase (MAPK) pathway, a signaling cascade crucial for
      the regulation of cell growth. This is consistent with the finding that efficient
      reduction of cell growth is limited to anthocyanidins that are potent EGFR- or
      PDE-inhibitors including cy and del or malvidin (mv), respectively. In summary,
      depending on the substitution pattern at the B-ring, anthocyanidins interfere
      with different signaling cascades involved in the regulation of cell growth.

PMID- 15497185
TI  - Meeting Diary: Mol. Nutr. Food Res. 4/2004.
AB  - No Abstract.

PMID- 15497184
TI  - The pig caecum model: a suitable tool to study the intestinal metabolism of
      flavonoids.
AB  - Pig caecum was used under anaerobic conditions to metabolize flavonoids from
      several classes, i.e., chrysin 1, naringenin 2, quercetin 3, and hesperetin 4.
      Whereas chrysin 1 was not converted by the pig intestinal flora under the
      experimental conditions used, naringenin 2 was transformed to 3-(4-hydroxyphenyl)
      propionic acid and 3-phenylpropionic acid. Quercetin 3 was metabolized to
      phloroglucinol, 3,4-dihydroxyphenylacetic acid, and 3,4-dihydroxytoluene.
      Hesperetin 4 was degraded via eriodictyol to 3-(3-hydroxyphenyl)-propionic acid
      and phloroglucinol. Structural elucidation of the formed metabolites was
      performed by high-performance liquid chromatography--diode array detection (HPLC
      DAD) as well as HPLC-electrospray ionization--mass spectrometry (ESI-MS (MS)) and
      high resolution gas chromatography-mass spectrometry (HRGC-MS) analyses. The time
      course of microbial conversion of 2-4 was determined by HPLC-DAD analysis,
      revealing slow degradation of 2 and rapid transformation of 3 and 4. The results
      lead to the conclusion that the pig caecum model is a suitable ex vivo model for
      studying the intestinal degradation of flavonoids.

PMID- 15497187
TI  - Instructions to authors: Mol. Nutr. Food Res. 4/2004.
AB  - No Abstract.

PMID- 15497186
TI  - Impressum: Mol. Nutr. Food Res. 4/2004.
AB  - No Abstract.

PMID- 15497188
TI  - Outcome versus service based payments in health care: lessons from African
      traditional healers.
AB  - We compare the more common physician compensation method of fee-for-service to
      the less common payment-for-outcomes method. This paper combines an investigation
      of the theoretical properties of both of these payment regimes with a unique data
      set from rural Cameroon in which patients can choose between outcome and service
      based payments. We show that consideration of the role of patient effort in the
      production of health leads to important differences in the performance of these
      contracts. Theory and empirical evidence show that when illnesses require (or are
      responsive to) large amounts of both patient and practitioner effort, outcome
      based payment schemes are superior to effort based schemes. The traditional
      healer--a practitioner who offers health services on an outcome-contingent basis-
      is advanced as an important example of how patient effort can be better
      understood and tapped in health care.

PMID- 15497189
TI  - The importance of age in allocating health care resources: does intervention-type
      matter?
AB  - BACKGROUND: Recent proposals to reform cost-effectiveness analysis (CEA) by
      weighting health benefits [(Quality-adjusted life-years) QALYs] by recipients'
      age are based on studies examining age-related preferences in life-saving
      contexts. We investigated whether the perceived importance of age in resource
      allocation decisions differs among intervention-types. METHODS: 160 individuals
      were recruited from a cafeteria of a university medical centre and asked to
      choose between hypothetical health care programmes. Scenario A described two
      programmes treating life-threatening conditions and Scenario B two programmes
      providing palliative care. Programmes were identical except in average patient
      age (35 versus 65). Respondents also directly rated the importance of age for
      allocating resources for six types of interventions. RESULTS: Responses for the
      life-saving scenario favoured younger age groups while those for the palliative
      care scenario showed no age preference. The difference between scenarios was
      statistically significant. When directly rating the importance of age in
      allocating treatment resources, people placed greatest importance on age in
      treating infertility and life-saving, and least importance in treating
      depression. DISCUSSION: The importance people place on age as a resource
      allocation criterion depends on the clinical context. As QALYs serve as a common
      measure of health benefits for all intervention types, age weighting of QALYs is
      premature.

PMID- 15497191
TI  - Effects of socio-economic status on mortality: separating the nearby from the
      farther away.
AB  - Socio-economic status effects on total and cause-specific mortality are studied
      using data on all 15.8 million inhabitants of the Netherlands in 1999. Two
      problems are addressed that often hamper this kind of research: the lack of
      reliable social status information at the individual level and the intermingling
      of individual and neighbourhood status effects. The first problem is dealt with
      by using socio-economic status information of the very close environment of the
      detailed postcode areas (average 41 inhabitants) in which one is living and the
      second one by combining this information with such area information at the much
      larger level of neighbourhoods (1500 inhabitants) or boroughs (6600 inhabitants).
      Clear and independent effects of socio-economic status at all three levels of
      aggregation are found on total mortality and for a majority of causes of death.
      In almost all cases, the effects are to the disadvantage of people living in the
      lowest status areas. The effects are generally strongest at the detailed postcode
      level and weakest at the borough level, suggesting greater importance of factors
      at the nearby or individual level than at the farther away level(s).

PMID- 15497192
TI  - Effect of Tai Chi on depressive symptoms amongst Chinese older patients with
      depressive disorders: a randomized clinical trial.

PMID- 15497193
TI  - Donepezil and cardiac syncope: case report.

PMID- 15497194
TI  - 5-HT2A receptor polymorphism may modulate antipsychotic treatment response in
      Alzheimer's disease.

PMID- 15497195
TI  - 'Immigrant paid caregivers' and primary caregivers' burden.

PMID- 15497196
TI  - Technology and managed care: patient benefits of telemedicine in a rural health
      care network.
AB  - Rural health providers have looked to telemedicine as a technology to reduce
      costs. However, virtual access to physicians and specialists may alter patients'
      demand for face-to-face physician access. We develop a model of service demand
      under managed care, and apply the model to a telemedicine application in rural
      Alaska. Provider-imposed delays and patient costs were highly significant
      predictors of patient contingent choices in a survey of ENT clinic patients. The
      results suggest that telemedicine increased estimated patient benefits by about
      $40 per visit, and reduced patients' loss from rationing of access to physicians
      by about 20%.

PMID- 15497197
TI  - The welfare loss from hospital cost-shifting behavior: a partial equilibrium
      analysis.
AB  - Cost shifting occurs when changes in administered prices of one payer lead to
      compensating changes in prices charged to other payers. Microeconomic theory
      suggests that cost shifting can take place under limited conditions and some
      empirical studies indicate that that hospital cost shifting may have actually
      occurred at various times. This study designs a model to conceptualize and
      quantify the potential welfare loss caused by hospital cost shifting under
      idealized yet fairly plausible conditions. The resulting estimate yields only a
      small efficiency loss of at most, 0.84% of private hospital expenditures in the
      US for 1992.

PMID- 15497198
TI  - Estimating mean QALYs in trial-based cost-effectiveness analysis: the importance
      of controlling for baseline utility.
AB  - In trial-based cost-effectiveness analysis baseline mean utility values are
      invariably imbalanced between treatment arms. A patient's baseline utility is
      likely to be highly correlated with their quality-adjusted life-years (QALYs)
      over the follow-up period, not least because it typically contributes to the QALY
      calculation. Therefore, imbalance in baseline utility needs to be accounted for
      in the estimation of mean differential QALYs, and failure to control for this
      imbalance can result in a misleading incremental cost-effectiveness ratio. This
      paper discusses the approaches that have been used in the cost-effectiveness
      literature to estimate absolute and differential mean QALYs alongside randomised
      trials, and illustrates the implications of baseline mean utility imbalance for
      QALY calculation. Using data from a recently conducted trial-based cost
      effectiveness study and a micro-simulation exercise, the relative performance of
      alternative estimators is compared, showing that widely used methods to calculate
      differential QALYs provide incorrect results in the presence of baseline mean
      utility imbalance regardless of whether these differences are formally
      statistically significant. It is demonstrated that multiple regression methods
      can be usefully applied to generate appropriate estimates of differential mean
      QALYs and an associated measure of sampling variability, while controlling for
      differences in baseline mean utility between treatment arms in the trial.

PMID- 15497199
TI  - Testing the internal consistency of the lottery equivalents method using health
      outcomes: a comment to Oliver.

PMID- 15497200
TI  - Biological natural retting for determining the hierarchical structuration of
      banana fibers.
AB  - Extraction processes of natural fibers can be performed by different procedures
      that include mechanical, chemical and biological methods. Each method presents
      different advantages or drawbacks according to the amount of fiber produced or
      the quality and properties of fiber bundles obtained. In this study, biological
      natural retting was satisfactorily used for obtaining banana fibers from plant
      bunches. However, the most important contribution of this work refers to the
      description of the hierarchical microstructural ordering present in banana fiber
      bundles in both bundle surface and inner region. The chemical composition of
      banana fiber bundles has been evaluated by FTIR spectroscopy. Through exposure
      time, the fiber bundle configuration presents small variations in composition.
      The main changes are related to hemicellulose and pectins as they conform the
      outer walls of the bundle. Hierarchical helicoidal ordering in the bundle surface
      as well as orientation on the longitudinal axis of the bundle were observed by
      optical microscopy (OM) and scanning electron microscopy (SEM) for 3-4 microm
      surface fibers and 10-15 microm inner elementary fibers, respectively. With
      increasing exposure time, fiber bundle walls lose integrity, as reflected in
      their mechanical behavior.

PMID- 15497201
TI  - Correcting for compensating mechanisms related to productivity costs in economic
      evaluations of health care programmes.
AB  - In the economic evaluation of health care programmes, productivity costs are
      often estimated using patients' wages for the period of absence. However, the use
      of such methods for short periods of absence is controversial. A previous study
      found that short-term absence is often compensated for during normal working
      hours and therefore does not lead to productivity losses. As such, the
      application of any approach almost certainly overestimates productivity costs. In
      this study, we examined the productivity costs for five different patient
      populations and one employee population, using the classical method and by
      identifying when extra effort was needed. In general, the results showed that
      productivity costs based on identifying extra effort were 25-30% of the classical
      estimates. For absences of just one day, productivity costs were relevant in only
      17-19% of cases. For absences of two weeks or longer, productivity costs were
      relevant in 35-39% of cases. Measurement of the compensating mechanisms seemed to
      be valid, since there is considerable agreement between the opinion of
      supervisors and their employees about whether compensation covers productivity
      costs. There was much less agreement between supervisors and their employees on
      specific compensating mechanisms, however. The measurement of compensating
      mechanisms also seemed to be valid, because--as expected--different compensating
      mechanisms were reported for different occupations. In our study populations,
      compensating mechanisms appeared to differ with occupational characteristics,
      like part-time work, managerial work and shift work.

PMID- 15497202
TI  - Using covariates to reduce uncertainty in the economic evaluation of clinical
      trial data.
AB  - As part of their practice, policymakers have to make economic evaluations using
      clinical trial data. Recent interest has been expressed in determining how cost
      effectiveness analysis can be undertaken in a regression framework. In this
      respect, published research basically provides a general method for prognostic
      factor adjustment in the presence of imbalance, emphasizing sub-group analysis.
      In this paper, we present an alternative method from a Bayesian approach. We
      propose the use of covariates in Bayesian health technology assessment in order
      to reduce uncertainty about the effect of treatments. We show its advantages by
      comparison with another published method that do not adjust for covariates using
      simulated data.

PMID- 15497203
TI  - Reagan, Clinton, tobacco, and children: an interview with C. Everett Koop.
AB  - At eighty-seven years of age, former Surgeon General C. Everett Koop has an
      extraordinary perspective on health and medicine in America. He reflects on child
      health from his thirty-five years as a pediatric surgeon; AIDS from his position
      as Surgeon General at the outset of the epidemic; Presidents Reagan and Clinton,
      with whom he worked extensively; and smoking from his long battle first in
      government and then later as public antagonist to what he sees as the duplicitous
      and deceptive "killer" industry: tobacco.

PMID- 15497204
TI  - Review of current literature.

PMID- 15497205
TI  - Decreased likelihood [correction of likelyhood] of infants contracting HIV when
      taking nevirapine.

PMID- 15497206
TI  - Nematode molecular diagnostics: from bands to barcodes.
AB  - Nematodes are considered among the most difficult animals to identify. DNA-based
      diagnostic methods have already gained acceptance in applications ranging from
      quarantine determinations to assessments of biodiversity. Researchers are
      currently in an information-gathering mode, with intensive efforts applied to
      accumulating nucleotide sequence of 18S and 28S ribosomal genes, internally
      transcribed spacer regions, and mitochondrial genes. Important linkages with
      collateral data such as digitized images, video clips and specimen voucher web
      pages are being established on GenBank and NemATOL, the nematode-specific Tree of
      Life database. The growing DNA taxonomy of nematodes has lead to their use in
      testing specific short sequences of DNA as a "barcode" for the identification of
      all nematode species.

PMID- 15497207
TI  - Transdermal fentanyl (Duragesic): respiratory arrest in adolescents.

PMID- 15497208
TI  - Infliximab (Remicade) adn etanercept (Enbrel): serious infections and
      tuberculosis.

PMID- 15497209
TI  - Products containing bitter orange or synephrine: suspected cardiovascular adverse
      reactions.

PMID- 15497210
TI  - Ibutilide (Corvert): suspected association with torsades de pointes.

PMID- 15497211
TI  - Tubersol and anaphylaxis.

PMID- 15497212
TI  - The genetic make-up of renal cell tumors.
AB  - Recent developments in (molecular genetics have led to a better understanding of
      renal tumor biology. The current knowledge of the genetics of benign as well as
      malignant renal tumors is discussed briefly. This knowledge may, in the near
      future, be used to more accurately diagnose these tumors and also to optimalize
      individually based therapy.

PMID- 15497213
TI  - Bacterial translocation in experimental uremia.
AB  - The aim of this study was to investigate whether or not experimental uremia would
      induce bacterial translocation. Forty male Wistar rats were randomized into two
      groups: uremic (n = 20) and control (n = 20). Under anesthesia, the upper and
      lower left renal poles and the marginal lateral parenchyma were excised in uremic
      group. Seven days later, in a second operation, the liver, spleen and the
      mesenteric lymph nodes (MLN) were excised and cultured. Blood samples were sent
      for biochemical analysis (BUN, creatinine, sodium and potassium) and cultured.
      Specimens of the jejunum (1 cm below the Treitz angle) and ileum (1 cm above the
      ileocecal valve) were collected and sent for histological examination and scored
      for the degree of inflammation of the mucosa using a classification proposed by
      Chiu et al. in 1970. Uremic rats presented higher BUN, creatinine and potassium
      than controls. Bacterial translocation was more frequent in uremic than in
      control animals (8/20 (40%) vs. 1/20 (5%); p = 0.02). Translocation in uremic
      rats was observed mainly at the MLN (all eight cases). Both at the jejunum
      (uremic = 3 [0-5] vs. control = 2 [0-4]; p = 0.04) and the ileum (uremic - 2 [0
      5] vs. control = 0 [0-3]; p = 0.01), inflammation score was higher in uremic rats
      than in controls. The intestinal mucosa barrier is impaired and bacterial
      translocation occurs in experimental uremia.

PMID- 15497214
TI  - Odontoma of the middle ear: a case presentation. 1975.

PMID- 15497215
TI  - The sequencing of the rat genome.

PMID- 15497216
TI  - Impact of current treatment guidelines on minority patients with HIV infection.
AB  - Guidelines regarding treatment of HIV/AIDS are frequently updated in response to
      the growing complexity of antiretroviral medicine and the volume of data emerging
      from clinical research. Since april 1998, the Department of Health and Human
      Services has issued 11 updates of its Guidelines for the Use of Antiretroviral
      Agents in HIV-1-Infected Adults and Adolescents. These guidelines impact
      physician practice in the treatment of HIV-infected patients of multiple races
      and ethnicities, though their benefit in improving outcomes in minority patient
      populations is not fully understood.

PMID- 15497217
TI  - Impact of resistance to antiretroviral therapy in the minority community.
AB  - The development of resistance to antiretroviral therapies has become a formidable
      barrier to providing optimal treatment of HIV infection in the United States. The
      emergence of new mutations resistant to antiretroviral agents and a rise in
      transmission of resistant viruses contribute to an increased risk of treatment
      failure. Resistance testing of both treatment-experienced and treatment-naive
      patients i snow recommended for identification of the most effective treatment
      regimen; however, resistance testing is not universally available or easily
      interpreted. Furthermore, poor adherence to a treatment regimen or treatment with
      less potent antiretroviral agents can lead to exposure of virus to subinhibitory
      levels of drug and the development of resistance. In this article, we discuss
      several issues that specifically impact the development and transmission of
      resistant HIV in patients belonging to ethnic minorities and teh implementation
      of strategies that will overcome resistance as an obstacle to optimal treatment.

PMID- 15497218
TI  - Recognizing and managing common toxicities in patients receiving antiretroviral
      therapy.
AB  - Each of the 3 traditional classes of antiretroviral drugs (nucleoside/nucleotide
      reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors,
      and protease inhibitors [PIs]) has characteristic sets of toxicities that are not
      found with the other drug classes. On the other hand, lipodystrophy, which was
      thought to be specific to PIs, is now known to be common to all 3 classes of
      drugs. An understanding of the drug-specific, class-specific, and general
      toxicities and side effects of antiretroviral drugs will help the clinician
      tailor treatment regimens to individual patients.

PMID- 15497219
TI  - Hepatitis C virus and HIV coinfection: clinical management and new strategies.
AB  - Approximately one third of all HIV-infected people are coinfected with hepatitis
      C virus (HCV). The progression from initial HCV infection to cirrhosis of the
      liver is accelerated in coinfected patients compared with HCV-monoinfected
      patients. Because of improved therapies for HIV/AIDS, one of the leading causes
      of death for HIV-infected patients is liver disease. It is therefore important to
      screen all persons with HIV infection for the presence of HCV and to treat the
      HCV infection as appropriate. Treatment options need to be tailored to each
      patient, depending on the severity of liver damage, the HCV genotype, and the
      willingness of the patient to receive therapy. Current first-line therapy for
      hepatitis C consists of pegylated interferon plus ribavirin. However, this
      therapy has only limited success in persons with HCV genotype 1 and in African
      Americans. In addition, the side effects of anti-HCV therapy can be considerable
      and require careful management. Improvement or delayed progression of fibrosis
      should be the main goal of therapy in most patients.

PMID- 15497220
TI  - African Americans and HIV/AIDS: cultural concerns.
AB  - AIDS is a disease that has had a disproportionate effect on African Americans.
      While there has been significant progress in the treatment of people with HIV
      infection, there are obstacles to the optimal treatment of African Americans,
      such as distrust of the medical system, cultural differences between patients and
      providers, and institutional racism. To optimize treatment of African Americans
      with HIV/AIDS, health care providers must learn more about cultural issues that
      impact treatment. The goals of treatment for African Americans with HIV infection
      are the same as those for all patients: maintain durable suppression of HIV
      replication, prevent resistance, support optimal immune system function, extend
      AIDS-free survival time, maximize adherence to antiretroviral regimens, and
      improve quality of life.

PMID- 15497221
TI  - HAART, adherence, and cultural issues in the US Latino community.
AB  - Latinos represent the largest and fastest growing minority group in the United
      States. They are a culturally diverse population united by a common Spanish
      language. Although they represent approximately 13% of the US population, Latinos
      account for 19% of diagnosed HIV cases and 20% of AIDS cases. Latinos typically
      present late in the course of the disease and face barriers to care, including
      limited health care access and the withholding of HAART by care providers.
      Adherence to HAART can be difficult to predict, but adherence can be improved
      through better patient-centered care and better provider understanding of Latino
      cultural issues and needs.

PMID- 15497222
TI  - Femoral injuries in modem warfare since Vietnam.

PMID- 15497223
TI  - Faculty matters. Joseph Colagreco.

PMID- 15497224
TI  - Who will remember you?

PMID- 15497225
TI  - Neurotoxicity of available root sealant pastes.

PMID- 15497226
TI  - Abandon the dead donor rule or change the definition of death?
AB  - Research by Siminoff and colleagues reveals that many lay people in Ohio classify
      legally living persons in irreversible coma or persistent vegetative state (PVS)
      as dead that additional respondents, although classifying such patients as
      living, would be willing to procure organs from them. This paper analyzes
      possible implications of these findings for public policy. A majority would
      procure organs from those in irreversible coma or in PVS. Two strategies for
      legitimizing such procurement are suggested. One strategy would be to make
      exceptions to the dead donor rule permitting procurement from those in PVS or at
      least those who are in irreversible coma while continuing to classify them as
      living. Another strategy would be to further amend the definition of death to
      classify one or both groups as deceased, thus permitting procurement without
      violation of the dead donor rule. Permitting exceptions to the dead donor rule
      would require substantial changes in law--such as authorizing procuring surgeons
      to end the lives of patients by means of organ procurement--and would weaken
      societal prohibitions on killing. The paper suggests that it would be easier and
      less controversial to further amend the definition of death to classify those in
      irreversible coma and PVS as dead. Incorporation of a conscience clause to permit
      those whose religious or philosophical convictions support whole-brain or cardiac
      based death pronouncement would avoid violating their beliefs while causing no
      more than minimal social problems. The paper questions whether those who would
      support an exception to the dead donor rule in these cases and those who would
      support a further amendment to the definition of death could reach agreement to
      adopt a public policy permitting organ procurement of those in irreversible coma
      or PVS when proper consent is obtained.

PMID- 15497227
TI  - The dead donor rule: lessons from linguistics?
AB  - American society traditionally has assumed a univocal notion of "death," largely
      because we have only one word for it and, until recently, have not needed a more
      nuanced notion. The reality of death-processes does not preclude the reality of
      death events. Linguistically, "death" can be understood only as an event; there
      are other words for the process. Our death vocabulary should expand to reflect
      multiple events along the process from sickness to decomposition. Depending on
      context, some death-related events may constitute a more obvious discontinuity
      than others and more justifiably may be considered "death" within that context.
      There is no reason to assume a priori that there must be an overarching, unitary
      concept of death from which all diagnostic criteria must derive. Regarding organ
      transplantation, the relevant question is not "Is the patient dead?" but rather
      "Can organs X, Y, Z ... be removed without causing or hastening death or harming
      the patient?"

PMID- 15497228
TI  - Harvesting the living?: separating "brain death" and organ transplantation.
AB  - The chronic shortage of transplantable organs has reached critical proportions.
      In the wake of this crisis, some bioethicists have argued that there is
      sufficient public support to expand organ recovery through use of neocortical
      criteria of death or even pre-mortem organ retrieval. I present a typology of
      ways in which data gathered from the public can be misread or selectively used by
      bioethicists in service of an ideological or policy agenda, resulting in bad
      policy and bad ethics. Such risks should lead us to look at alternatives for
      increasing organ supplies short of expanding or abandoning the dead donor rule.
      The chronic problem of organ scarcity should prompt bioethicists to engage in
      constructive dialogue about the relation of the social sciences and bioethics, to
      examine the social malleability of the definition of death, and to revisit the
      question of the priority of organ transplants in the overall package of
      healthcare benefits provided to most, but not all, citizens.

PMID- 15497229
TI  - The dead donor rule: how much does the public care...and how much should we care?
AB  - In this brief commentary, we reflect on the recent study by Siminoff, Burant, and
      Youngner of public attitudes toward "brain death" and organ donation, focusing on
      the implications of their findings for the rules governing from whom organs can
      be obtained. Although the data suggest that many seem to view "brain death" as
      "as good as death" rather than "dead" (calling the dead donor rule into
      question), we find that the study most clearly demonstrates that understanding an
      individual's definition of death is neither a straightforward task nor a good
      predictor of views about donation. Reflecting on the implications for ongoing
      debates over the dead donor rule, we suggest that perhaps it is not a change in
      policy that is warranted, but rather a change in the priorities that have
      garnered such intense focus on this issue within the field of bioethics.

PMID- 15497230
TI  - Smokers' rights to health care: why the 'restoration argument' is a moralising
      wolf in a liberal sheep's clothing.
AB  - Do people who cause themselves to be ill (e.g. by smoking) forfeit some of their
      rights to healthcare? This paper examines one argument for the view that they do,
      the restoration argument. It goes as follows. Smokers need more health-resources
      than non-smokers. Given limited budgets, we must choose between treating everyone
      equally (according to need) or reducing smokers' entitlements. This paper
      criticises the restoration argument on the following grounds. In order to avoid
      generating unpalatable conclusions elsewhere, it must be combined with a
      principle according to which activities which are sufficiently 'socially
      valuable' (e.g. parenting) are immune from restoration claims. This however means
      that what was supposed to be one of the argument's most attractive features, its
      compatibility with 'liberal neutrality' with respect to the values of different
      lifestyles, doesn't really exist. Hence, the restoration argument is nowhere near
      as attractive as it first appears to be.

PMID- 15497231
TI  - Setting bioethics in context.

PMID- 15497232
TI  - Animal dispute.

PMID- 15497233
TI  - Comments: implications of hormesis for industrial hygienists.
AB  - Quantitative health risk assessment is based on extrapolating from the high-dose
      end of the dose-response curve to points close to the origin or the threshold
      where the dose levels are closer to the lower environmental or occupational
      exposures. Hormesis is demonstrated in chronic toxicological studies where the
      animals treated at the lowest experimental dose appear to be healthier than the
      controls, as evidenced by longer life spans, less disease and/or increased body
      weight. If the occupational exposure limit (OEL) or environmental exposure limit
      (EEL) is in the range of the hormetic effect, or lower than the hormetic effect,
      then a case could be made that exposure at the OEL or EEL is 'safe.' This idea is
      controversial because it challenges some of the basic assumptions of quantitative
      health risk assessment as it has been practiced during the past 50 years. De
      emphasis of the dose-response curve in determining OELs and EELs will occur not
      because of hormesis, but because the emerging sciences of genomics and proteomics
      will shift the focus from statistical methods to individuals as genetic and
      protein engineering becomes more sophisticated and powerful.

PMID- 15497234
TI  - In drug research, some guinea pigs are now human.

PMID- 15497235
TI  - Abdominal pain in a patient with AIDS.

PMID- 15497236
TI  - Review of "Implications of Hormesis for Industrial Hygiene".
AB  - Hormesis is an appealing concept when considered from the evolutionary viewpoint.
      It may provide a new approach to deriving the "no observed adverse effect level"
      for occupational exposures to chemicals. An over-reliance on mathematical
      modeling without a clear understanding of exposures and health outcomes stymies
      current scientific decision-making. Care must be taken, however, as not all
      endpoints will exhibit a hormetic response.

PMID- 15497237
TI  - Abstracts from the 11th International Congress on Twin Studies. Denmark, 1-4 July
      2004.

PMID- 15497238
TI  - Comments on "Implications of Hormesis for Industrial Hygiene".
AB  - Although demonstrated evidence for hormesis of an agent could be important in
      setting occupational exposure limits (OELs) for industrial hygiene, several
      practical problems may limit the utility of toxicologic testing for hormesis.
      This commentary responds to the lead article of this section, in which Jayjock
      and Lewis propose using the results of tests for hormesis to guide the
      establishment of OELs. The principal difficulties may include: a different
      mechanism or even a different effect leading to the conclusion of hormesis;
      distinction between a threshold for a health effect and a crossover point in the
      dose response relationship; estimation of threshold or crossover point from
      limited test data and estimation of slope at this point; sensitivity of tests for
      hormesis; and cost of testing. Nevertheless, the proposals of Jayjock and Lewis
      have considerable merit, and exploratory testing could be useful.

PMID- 15497239
TI  - Hormesis: the new approach in risk assessment?
AB  - Hormesis is a dose-response phenomenon characterized by either a U-shaped or an
      inverted U-shaped dose response depending on the different end points measured.
      In a paper in this issue of the journal, Drs Jayjock and Lewis advocate for the
      application of hormesis in the field of industrial hygiene, and suggest the use
      of hormesis as a default assumption in the risk assessment process. However,
      there are many difficulties for the utilization of hormesis in the field of
      industrial hygiene. Indeed, it is impossible to test the hormesis hypothesis in
      many commonly employed experimental model systems for end points of public health
      concern, and the mechanism of low-dose stimulation of hormesis is not clear. Even
      if hormesis were proven biologically, its assessment is limited due to
      difficulties of study design, biological markers selection, statistical power
      considerations, model and end point selection, and risk model approaches.

PMID- 15497240
TI  - Hormesis and industrial hygiene: a new hypothesis for low-dose response in
      occupational risk assessment.
AB  - The study of Jayjock and Lewis, 'Implication of Hormesis for Industrial Hygiene',
      represents a challenge for the scientific community to consider hormesis as a
      possible working hypothesis for redefining risk assessment strategy for low-dose
      exposures in the realm of industrial hygiene. This invited commentary aims at
      examining some aspects of the study for which no proven and conclusive scientific
      evidence has yet been found, such as the limited nature of some statistical
      tests, the calculation of the safety factor, the place occupied by hormesis in
      industrial hygiene and, finally, the impact that scarce knowledge of this
      phenomenon and rejection by part of the scientific community has on the
      possibility of using hormesis in the safeguarding of workers' health.

PMID- 15497241
TI  - Comments on the Jayjock et al. paper.
AB  - Establishing hormesis as an evolution-based biological phenomenon requires a
      broad discussion of its implications for currently used risk paradigms. The
      Jayjock et al. papers provide an industrial hygienist's perspective and, as such,
      represent a valuable contribution to this discussion. Our comments outline a
      toxicologist's view on the limits and practicability of the Jayjock et al.
      suggestions. The arguments are primarily based on the shape of dose and time
      responses and associated variabilities and uncertainties.

PMID- 15497242
TI  - Non-Hodgkin's Lymphoma: Current Status and Future Prospects. Proceedings of the
      1st International Workshop on Non-Hodgkin's Lymphoma. November 2002, Chantilly,
      France.

PMID- 15497244
TI  - What price education?

PMID- 15497243
TI  - Jayjock and Lewis reply.
AB  - The current state-of-the-science, in our opinion, is incapable of accurately
      predicting the human health risk at environmental exposures to chemicals. We
      believe that dose-response models represent an integral part of the scientific
      method but that all models require valid scientific data in the realm of actual
      exposure in order to be derived and function properly. Given this current state,
      the evidence to date and the promise of hormesis to provide a detectable signal
      at low-dose, we view it as a variable and valuable hypothesis worthy of
      significant scientific effort.

PMID- 15497245
TI  - Written description.

PMID- 15497246
TI  - Jonathan K. C. Knowles discusses the impact of pharmacogenomics on market
      segmentation.

PMID- 15497247
TI  - Pemetrexed disodium.

PMID- 15497248
TI  - Missed opportunities in pharma?

PMID- 15497249
TI  - Proceedings of the 4th Nestle Nutrition Conference: Loss of Homeostasis in Body
      Weight Regulation.

PMID- 15497250
TI  - Drugs, alcohol, and accidental death coverage.
AB  - Accidental death policies insure against what their name implies, but what is an
      accidental death? This is often not a question easily answered, and when alcohol
      and drugs (prescribed or illegal) are the causes of, or contributors to, the
      death, the issue becomes even thornier, and highly fact- and jurisdiction
      specific. As this survey shows, the law in this area is inconsistent but
      nevertheless susceptible of coherent and organized analysis.

PMID- 15497251
TI  - A primer on case law under the Americans with Disabilities Act.
AB  - This article provides a comprehensive guide through the Americans with
      Disabilities Act. It discusses highlights of the statutory scheme, and surveys
      many of the cases decided under the Act, by subject matter.

PMID- 15497252
TI  - A barium marking method using an ultrathin bronchoscope with virtual
      bronchoscopic navigation.
AB  - CT scanning in a 77-year-old woman showed a ground-glass opacity pattern shadow(9
      x 7 mm) in the right lower lobe. To allow identification of the location of the
      lesion during thoracoscopic surgery, preoperative barium marking was performed
      using an ultrathin bronchoscope and virtual bronchoscopic navigation. Virtual
      bronchoscopy was performed based on thin-section CT images, and virtual
      bronchoscopic images to the target sites were obtained. Subsequently, using
      virtual bronchoscopic images to right B8aiibetax, B6biibeta for navigation, an
      ultrathin bronchoscope was advanced to this site under direct observation. A
      special catheter for ultrathin bronchoscopy was advanced to sites near the
      lesion, and barium was infused. Barium was clearly observed by radiographic
      fluoroscopy during thoracoscopic surgery and was useful for determining the area
      for resection. Pathological examination of the resected specimen revealed
      atypical adenomatous hyperplasia. There were no complications with this method,
      and a number of target areas could be readily marked in a short time. This method
      may be useful before thoracoscopic surgery for small peripheral pulmonary
      lesions.

PMID- 15497253
TI  - Primary lung involvement with amyloid deposition in Waldenstom's
      macroglobulinemia: observations from over 20 years.
AB  - Primary lung involvement in Waldenstrom's macroglobulinemia (WM) is rare. The
      present case had lymphoplasmacytic lymphoma, secreting monoclonal IgM, localized
      to the lung.WM is also of great interest with regard to the pathogenesis of
      amyloidosis. The nodular, parenchymal amyloid lesions of the lung are presented
      with CXR observations of more than 20 years.

PMID- 15497254
TI  - Pulmonary alveolar proteinosis associated with psoriasis and complicated by
      mycobacterial infection: successful treatment with granulocyte-macrophage colony
      stimulating factor after a partial response to whole lung lavage.
AB  - Pulmonary alveolar proteinosis (PAP) is a rare lung disease. Although whole lung
      lavage is considered the most effective treatment, not every patient shows a
      complete response. The case ofa young man with PAP in association with psoriasis
      who underwent frequent whole lung lavage but only achieved remission following
      treatment with granulocyte-macrophage colony stimulating factor (GM-CSF) is
      reported. His lung problem was complicated by atypical mycobacterial
      infection,which resolved with treatment. The role of GM-CSF is discussed.

PMID- 15497255
TI  - What is the 'appropriate' term for saline nose drops: placebo or drug?

PMID- 15497256
TI  - Prospective timing under dual-task paradigms: attentional and contextual-change
      mechanisms.
AB  - The effect of a concurrent memory task on prospective time estimates by human
      participants was investigated in two experiments. The objective was to isolate
      task effects from those of participant timing strategy (self-paced counting) and
      number of contextual changes during the temporal stimulus. Accordingly, self
      paced counting was suppressed by requiring participants to perform a word-reading
      task during the temporal stimuli, while number of stimulus changes presented
      during temporal stimuli was controlled. Presence versus absence of the concurrent
      memory task was manipulated in Experiment 1, and instruction to focus on timing
      or to focus on memory was manipulated in Experiment 2. There was no significant
      effect of presence versus absence of the concurrent memory task on time
      estimates; however, time estimates were shorter when participants were instructed
      to focus on memory versus timing. In both experiments, time estimates were
      positively correlated with participants' estimates of the number of words
      presented during the interval, even though number of words presented was
      invariant. These findings were generally consistent with resource-allocation
      attentional accounts of concurrent task effects; however, support for a
      contextual-change model of timing was also obtained.

PMID- 15497257
TI  - Comparison of the behaviour of European brown bears (Ursus arctos arctos) in six
      different parks, with particular attention to stereotypies.
AB  - In order to assess the influence of environmental parameters on their behaviour,
      16 European brown bears were observed in six different zoological parks.
      Activities were measured by scan sampling and their relationships to housing
      conditions were established by multifactorial correspondence analysis and cluster
      analysis. The largest enclosures were characterised by high scores of play,
      social behaviours, eating, and interest in the inside as well as the outside of
      the enclosure. Because these parks were newer, their bears were the youngest of
      those studied. Stereotypies were associated with medium age animals and small
      enclosures. The oldest subjects were characterised by high frequencies of
      resting. Stereotyped walk was observed only in those parks where keepers throw
      food to the bears. This result and detailed observation of stereotyped movements
      suggest that the meaning of the stereotypy for the animal could be to induce the
      keeper's arrival.

PMID- 15497258
TI  - Locomotion induced by non-contingent intracranial stimulation: comparison to
      psychomotor stimulant.
AB  - Non-contingent experimenter-applied stimulation (nEAS) to the ventral
      mesencephalon, unlike contingent intracranial self-stimulation (ICSS), elicits
      high rates of general locomotion. This locomotion may be due to the nature of the
      presentation of stimulation, in that nEAS is non-contingent, while ICSS depends
      on a specific and focused response (e.g., bar pressing). Psychomotor stimulants
      also elicit high amounts of general locomotion, with the locomotion attributed to
      increased dopamine release. Interestingly, dopamine release decreases or is
      absent with repeated ICSS, but not nEAS. This suggests that the locomotion
      elicited by nEAS may be the result of DA release similar to that observed with
      psychomotor stimulants. To determine the relationship between locomotion induced
      by nEAS and psychomotor stimulants, locomotion elicited by nEAS was directly
      compared to that produced by cocaine, a psychomotor stimulant and indirect DA
      agonist. Six groups of rats were examined: (1) DA+ group: rats were implanted
      with a stimulating electrode in the ventral mesencephalon and activation of DA
      neurons was verified during surgery by monitoring DA release in the striatum; (2)
      DA- group: rats were also implanted with stimulating electrodes, but the location
      in the ventral mesencephalon did not elicit DA release; (3) 10-mg/kg cocaine
      group: rats were exposed to a low dose (10 mg/kg) of cocaine; (4) 40-mg/kg
      cocaine group: rats were exposed to a high dose (40 mg/kg) of cocaine; (5) saline
      group: rats were injected with saline; and (6) naive group: rats received no
      treatment. The topography of behavior was assessed in all rats during four
      periods: a pre-treatment baseline, treatment, early post-treatment, and a late
      post-treatment end point. The results suggest that locomotion elicited by nEAS
      was stereotypic, dependent upon DA release and similar, but not identical, to
      psychomotor stimulant-induced locomotion.

PMID- 15497259
TI  - Categorical perception of orientation in monkeys.
AB  - Structural and functional substrates of orientation processing in monkeys have
      been clarified. However, orientation perception in monkeys has not been fully
      studied. In this study, the cognitive mechanism that controls monkeys' perception
      of orientation was evaluated. After the monkeys were trained to discriminate
      between a cardinal and an oblique orientation (e.g., 0 degrees and 30 degrees),
      their perceptual mechanisms underlying orientation discrimination were tested by
      using six orientations, ranging from 0 degrees to 150 degrees, including ones
      used in the discrimination training. Generalization tests showed that the monkeys
      who were trained with cardinal orientations (e.g., 0 degrees) as positive stimuli
      generalized their responses to the other cardinal orientation (e.g., 90 degrees).
      Similarly, the monkeys who were trained with oblique orientations (e.g., 30
      degrees) as positive stimuli generalized their responses to all other oblique
      orientations (e.g., 60 degrees, 120 degrees, and 150 degrees). These findings
      indicated that the monkeys abstracted the quality of the cardinal/oblique
      category from the physical features of orientation stimuli although they were not
      trained to do so. Such an abstraction also suggested a discrepancy between a
      continuously and orderly arranged cortical map and a discontinuously categorized
      perception of orientation. The present findings provide insight into the learning
      correlated plasticity of cortical orientation preference.

PMID- 15497260
TI  - Effects of rearing conditions on sand digging efficiency in juvenile cuttlefish.
AB  - The effect of environment on the maturation of sand digging behaviour in
      cuttlefish was studied. Sand digging behaviour of cuttlefish individually reared
      on sand was daily observed in their rearing tanks (first study). Other cuttlefish
      were individually reared from hatching to 2 weeks of life in different conditions
      (Group A, on a sandy substrate and group B, without sand). At days 0, 3, 6, 9, 12
      and 15, cuttlefish from Groups A and B were placed in a novel tank, the bottom of
      which was covered by sand (second study). The first study shows that more and
      more cuttlefish sand dig in their rearing tank during the first 6 days of life.
      The second study shows that, confronted with a novel sand bottom, cuttlefish from
      Group A show shorter latencies of sand digging and they cover more completely
      than do cuttlefish from Group B. This indicates that the developmental changes in
      sand digging appear not totally pre-programmed, but at least partially experience
      dependent. Presence of sand in rearing tanks may allow cuttlefish to acquire
      experience of digging to make this behaviour more efficient.

PMID- 15497261
TI  - Catch me if you can: hospitals battle to come clean on MRSA.

PMID- 15497262
TI  - Boys with reading disabilities and/or ADHD: distinctions in early childhood.
AB  - We examined distinctions in the early childhood characteristics of boys with
      reading disabilities (RD) and/or attention-deficit/ hyperactivity disorder
      (ADHD). A four-group mixed design consisting of boys identified at age 11 with
      reading disabilities only (RD only; n = 46), reading disabilities and ADHD
      (RD/ADHD; n = 16), ADHD only (n = 20), and a comparison group (n = 281) was
      utilized. Differences on receptive and expressive language and temperament for
      ages 3 and 5 were investigated. Analyses indicated that the boys from the RD-only
      group performed worse on measures of receptive and expressive language. The
      results also indicated that boys from the RD/ADHD groups consistently performed
      worse on measures of receptive language and exhibited more behaviors indicative
      of an undercontrolled temperament. In summary, we suggest that reading
      disabilities and ADHD represent moderately unique disorders that frequently co
      occur and are characterized by distinct developmental pathways.

PMID- 15497263
TI  - Role of visual attention in cognitive control of oculomotor readiness in students
      with reading disabilities.
AB  - This study investigated eye movement and comprehension therapy in Grade 6
      children with reading disabilities (RD). Both order of therapy and type of
      therapy were examined. Furthermore, the implications of visual attention in
      ameliorating reading disability are discussed. Thirty-one students with RD were
      identified using standardized reading comprehension tests. Eye movements were
      analyzed objectively using an infra-red recording device. Reading scores of
      participating children were 0.5 to 1 SD below the national mean. Testing took
      place before the start of therapy (T1) and was repeated after 12 weeks (T2) and
      24 weeks (T3) of therapy. One group of students had eye movement therapy first,
      followed by comprehension therapy; in the other group, the order was reversed.
      Data were evaluated using a repeated measures MANOVA and post hoc tests. At T1,
      mean reading grade was 2 years below grade level, and eye movement scores were at
      about Grade 2 level. Mean growth in reading comprehension for the total sample
      was 2.6 years (p < .01) at T3; equally significant improvement was measured in
      eye movements (p < .01). Learning rate in reading comprehension improved from 60%
      (T1) to 400% (T3). Although within-group differences were statistically
      significant, between-group differences were not significant for comprehension or
      eye movements. Order of therapy (comprehension first or eye movements first) was
      not significant. Improvements in within-group scores for comprehension and eye
      movements were consistently significant at T2 and T3. Eye movement therapy
      improved eye movements and also resulted in significant gains in reading
      comprehension. Comprehension therapy likewise produced improvement both in eye
      movement efficiency and in reading comprehension. The results support the notion
      of a cognitive link among visual attention, oculomotor readiness, and reading
      comprehension.

PMID- 15497264
TI  - Cerebellar tests differentiate between groups of poor readers with and without IQ
      discrepancy.
AB  - A comprehensive test battery, including phonological, speed, motor and cerebellar
      tasks, was administered to the entire cohort of two schools for children with
      learning disabilities. Testing was undertaken blind without accessing the
      psychometric data on the children. Children were then allocated to a discrepancy
      group on the basis of their IQ, with the majority (n = 29) classified as
      nondiscrepant (IQ < 90) and a smaller set (n = 7), with IQ of at least 90,
      classified as discrepant (with dyslexia). Both groups showed significant deficits
      relative to age-matched controls on almost all the tests. On phonological, speed,
      and motor tasks, the nondiscrepant group were at least as severely impaired as
      the discrepant group. By contrast, on the cerebellar tests of postural stability
      and muscle tone, the nondiscrepant group performed significantly better than the
      children with dyslexia and close to the level of the controls. The findings
      indicate that cerebellar tests may prove a valuable method of differentiating
      between poor readers with and without IQ discrepancy. The findings are
      interpreted in terms of the cerebellar deficit hypothesis for dyslexia.

PMID- 15497265
TI  - Accuracy of teacher assessments of second-language students at risk for reading
      disability.
AB  - This study examined the accuracy of teacher assessments in screening for reading
      disabilities among students of English as a second language (ESL) and as a first
      language (L1). Academic and oral language tests were administered to 369 children
      (249 ESL, 120 L1) at the beginning of Grade 1 and at the end of Grade 2.
      Concurrently, 51 teachers nominated children at risk for reading failure and
      completed rating scales assessing academic and oral language skills. Scholastic
      records were reviewed for notation of concern or referral. The criterion measure
      was a standardized reading score based on phonological awareness, rapid naming,
      and word recognition. Results indicated that teacher rating scales and
      nominations had low sensitivity in identifying ESL and L1 students at risk for
      reading disability at the 1-year mark. Relative to other forms of screening,
      teacher-expressed concern had lower sensitivity. Finally, oral language
      proficiency contributed to misclassifications in the ESL group.

PMID- 15497266
TI  - A case study of the apprenticeship process: another perspective on the apprentice
      and the scaffolding metaphor.
AB  - This study focused on the apprenticeship opportunities in a collaborative writing
      context. The examination of written artifacts and discursive interactions
      revealed that collaborative contexts offered unique participatory spaces that
      allowed students to use their knowledge in ways that exceeded their independent
      competence. Of note, too, is that the study revealed students' active and
      constructive role, refuting the perception that most students with disabilities
      are passive learners in the teaching-learning process. Implications of the study
      further suggest the importance of peer collaborations in creating successful
      literacy apprenticeships, as well as in providing teachers with greater insight
      into the developmental progress and literacy potentials of their students in the
      context of situated literacy activity.

PMID- 15497267
TI  - Features of an interactive writing discourse: conversational involvement,
      conventional knowledge, and internalization in "Morning Message".
AB  - This study describes how meaning potentials were constructed in the literacy
      event known as Morning Message. Morning Message provided teachers and students
      with opportunities to construct a written text around the experiences of one
      student. This discourse of writing allowed for the examination of how meaning was
      orchestrated and scaffolded between the teacher and her students. Three findings
      are discussed, including the function of a series of conversational involvement
      moves utilized by the teacher, the specific writing conventions and metamessages
      afforded in the Morning Message dialogue, and an examination of how the social
      dialogues of Morning Message may have come to guide independent action as
      internalized processes on several transfer measures.

PMID- 15497268
TI  - Relation between Kaufman Brief Intelligence Test and WISC-III scores of children
      with RD.
AB  - Concurrent validity of the Kaufman Brief Intelligence Test (K-BIT) with the
      Wechsler Intelligence Scale for Children-Third Edition (WISC-III) was evaluated,
      as well as the K-BIT's accuracy as a predictor of WISC-III scores, in a sample of
      young children with reading disabilities. The two measures were administered to
      65 children from Atlanta, Boston, and Toronto who ranged from 6-5 to 7-11 years
      of age at testing. Correlations between the verbal, nonverbal, and composite
      scales of the K-BIT and WISC-III were .60, .48, and .63, respectively. Mean K-BIT
      scores ranged from 1.2 to 5.0 points higher than the corresponding WISC-III
      scores. Standard errors of estimation ranged from 10.0 to 12.3 points. In
      individual cases, K-BIT scores can underestimate or overestimate WISC-III scores
      by as much as 25 points. Results suggest caution against using the K-BIT
      exclusively for placement and diagnostic purposes with young children with
      reading disabilities if IQ scores are required.

PMID- 15497269
TI  - Early case reports of dyslexia in the United States and Europe.
AB  - Current understanding of reading disabilities is rooted in the early observations
      of physicians dating as far back in history as the 17th century. This article
      reviews medical case study research from the United Kingdom, Germany, and the
      United States that identified characteristics, etiological factors, and treatment
      methods of reading disorders. The physicians involved provided rich descriptions
      of the personal struggles of individuals who lost the ability to read because of
      brain insult as well as of those who failed to achieve literacy because of
      reading disability. Although many of the theories that were advanced by these
      early researchers have not been supported by current investigations, others have
      been substantiated and withstand the test of time. This article also addresses
      the validity of case study research from an historic and current-day perspective.

PMID- 15497270
TI  - Teachers with learning disabilities: a view from both sides of the desk.
AB  - The purpose of this qualitative multicase study was to explore the perceptions of
      individuals who could speak from both sides of the special education desk--as
      students and as teachers. The three participants for this study each received
      special education services for learning disabilities while in school and were
      currently teaching students with learning disabilities. Specifically the study
      focused on how participants' past experiences with receiving special education
      services influenced their current practice as special education teachers.
      Participants' views on service delivery models, the importance of teacher
      expectations, and the value of conceiving a learning disability as a tool rather
      than a deficit are discussed.

PMID- 15497271
TI  - Intensive remedial instruction for children with severe reading disabilities:
      immediate and long-term outcomes from two instructional approaches.
AB  - Sixty children with severe reading disabilities were randomly assigned to two
      instructional programs that incorporated principles of effective instruction but
      differed in depth and extent of instruction in phonemic awareness and phonemic
      decoding skills. All children received 67.5 hours of one-to-one instruction in
      two 50-minute sessions per day for 8 weeks. Both instructional programs produced
      very large improvements in generalized reading skills that were stable over a 2
      year follow-up period. When compared to the growth in broad reading ability that
      the participants made during their previous 16 months in learning disabilities
      resource rooms, their growth during the intervention produced effect sizes of 4.4
      for one of the interventions and 3.9 for the other. Although the children's
      average scores on reading accuracy and comprehension were in the average range at
      the end of the follow-up period, measures of reading rate showed continued severe
      impairment for most of the children. Within 1 year following the intervention,
      40% of the children were found to be no longer in need of special education
      services. The two methods of instruction were not differentially effective for
      children who entered the study with different levels of phonological ability, and
      the best overall predictors of long-term growth were resource room teacher
      ratings of attention/behavior, general verbal ability, and prior levels of
      component reading skills.

PMID- 15497272
TI  - Developmental dyscalculia is a familial learning disability.
AB  - Whereas current evidence attests to a genetic component in the etiology of
      dyslexia and attention-deficit/hyperactivity disorder (ADHD), little is known
      about the role of genetics in developmental dyscalculia (DC). The objective of
      this study was to determine the familial aggregation of DC. Siblings and parents
      of children with DC were assessed for arithmetic, reading and attention
      disorders. The criteria for DC were an IQ higher than 85, poor performance in
      arithmetic, and a significant discrepancy between arithmetic achievement and IQ.
      The study group was composed of 39 children with DC, 21 mothers, 22 fathers, 90
      siblings, and 16 second-degree relatives. We found that 66% of mothers, 40% of
      fathers, 53% of siblings, and 44% of second-degree relatives had DC. The
      intraclass correlation between the sib pairs was .27. A 95% confidential interval
      (CI) for the prevalence of DC among siblings of DC probands (see Note 1) ranged
      from 40% to 64%, indicating a familial prevalence almost tenfold higher than
      expected for the general population. IQ and attention problems were not risk
      factors for DC. We conclude that DC, like other learning disabilities, has a
      significant familial aggregation, suggesting a role for genetics in the evolution
      of this disorder.

PMID- 15497273
TI  - The relation of LD and gender with emotional intelligence in college students.
AB  - This study examined the relation of learning disabilities (LD) and gender with
      emotional intelligence in 128 college students. Fifty-four students with LD (32
      men and 22 women) and 74 without LD (34 men and 40 women) attending two colleges
      and one university participated in the study. Emotional intelligence was assessed
      using the Emotional Quotient Inventory (EQ-i; BarOn,1997), a self-report
      instrument designed to measure interpersonal and intrapersonal skills, stress
      management, adaptability, and general mood. A 2-way multivariate analysis of
      variance (MANOVA) was performed to examine the main effects of LD and gender and
      the interaction of the two main effects on the five composites of the EQ-i.
      Students with LD had fewer credits and lower scholastic aptitude test (SAT)
      scores, high school grade point averages (GPAs), and college GPAs than students
      without LD; women students were older and had higher college GPAs than men
      students. Results of the MANOVA indicated significant main effects of both LD and
      gender; no significant interaction occurred. Post hoc univariate analyses of the
      five composites revealed significant differences between students with LD and
      students without LD on stress management and adaptability, significant
      differences between men and women students on interpersonal skills, and
      significant differences of the interaction of LD and gender on interpersonal
      skills.

PMID- 15497274
TI  - A reconceptualization of learning disabilities via a self-organizing systems
      paradigm.
AB  - A dilemma exists regarding the interpretation of learning disabilities. A self
      organizing systems (SOS) paradigm suggests widespread, diffuse outcomes, whereas
      a specific learning disability concept suggests more localized dysfunction. There
      may be very good reason to doubt the veridicality of the concept of a specific
      learning disability, not because the construct of learning disabilities itself is
      a frivolous concept, as some have held, but because the biological or
      neurological events that underlie a learning disability do not remain focal and
      constrained only to specific dysfunction. It is important to know whether an
      identified learning disability remains contained or whether processing disorders
      might be found in other areas. The assessment profiles of school-age children
      identified with nonverbal learning disabilities (NLD), assumed to have primarily
      right-hemispheric brain dysfunctions, and children with language-based learning
      disabilities (LLD), assumed to have primarily left-hemispheric brain
      dysfunctions, were examined to explore learning disabilities using an SOS
      paradigm. The pilot study reported here is used as an exemplar of how a self
      organizing systems paradigm is conceptualized. Although a more comprehensive
      study is needed to confirm the data, this exemplar suggests that overflow into
      areas not typically associated with each disability subtype may occur. Concerns
      regarding ways of determining discrepancy for diagnostic purposes are noted, and
      remediation strategies designed for specific disabilities are questioned.

PMID- 15497279
TI  - Walton Centre for Neurology and Neurosurgery NHS Trust: a centre specialising in
      excellence.

PMID- 15497280
TI  - Driving the IT plan ahead.

PMID- 15497281
TI  - Leading the switch to patient-centred care.

PMID- 15497282
TI  - Reducing the risks of parenteral nutrition.
AB  - Parenteral nutrition is a vital method of delivering essential nutrients to some
      patients. But if used inappropriately it can increase the risk of catheter
      related infection and incur unnecessary expense. Mary Bird explains how a
      nutritional support team's involvement transformed the quality of care for
      patients receiving the therapy at one trust.

PMID- 15497283
TI  - The growing input of specialist nurses in the health care of looked-after
      children.
AB  - Children in care suffer many health problems but are often reluctant to seek
      help. Recent policies have focused on changing the emphasis from treating
      sickness to regular assessments with a focus on well-being and health education.
      Nurses are playing an important part in putting this into practice, as Terry
      Philpot reports.

PMID- 15497284
TI  - Case study: a consultant nurse for looked after children.

PMID- 15497285
TI  - Back to the basics of wound care: why nurses should question their practice.
AB  - The high incidence of hospital-acquired infections, about a tenth of which occur
      in wounds, has propelled the issue of prevention to the top of the health-care
      agenda. Policy centres on hygiene, protective precautions and educating staff and
      patients. This article focuses on detection and treatment options for confirmed
      wound infections.

PMID- 15497286
TI  - How to get practical support and advice.

PMID- 15497287
TI  - How a health promotion model reduces disabling complications of diabetes.
AB  - Health promotion strategies provide a support framework for preventing ill health
      or reducing complications of chronic disease. This article explains the need for
      a strategy that embraces partnership working.

PMID- 15497288
TI  - Developing and piloting a structured, stepped approach to patient education.
AB  - The DESMOND initiative aims to provide patients with Type 2 diabetes with ongoing
      education about their condition from the point of diagnosis. The programme is in
      the process of developing a structured education curriculum that, combined with
      clinical management, will offer an integrated care pathway to patients.

PMID- 15497289
TI  - Handwashing: what is the best solution?
AB  - The options for keeping hands clean in hospital include soap; antimicrobial
      solutions; iodine and iodophours; and alcohol solutions and rubs. Following the
      recent directive for alcohol rubs to be placed at hospital bedsides, this paper
      considers the pros and cons of these and other hand-hygiene methods.

PMID- 15497290
TI  - Rationalising examination glove use to improve patient care and reduce costs.
AB  - An exercise to standardise glove use across three hospitals uncovered incorrect
      use of gloves in clinical practice. It also found that a wide range of gloves
      were being used for different purposes and procured at different costs. This
      paper explores the reasons and looks at strategies to streamline practice and
      achieve trust-wide standardisation and cost savings

PMID- 15497291
TI  - Diuretic drugs.
AB  - This group of drugs is commonly used to treat oedema in conditions ranging from
      congestive heart failure to raised intracranial pressure, where the aim is to
      increase urine output and the amount of sodium and other electrolytes excreted in
      urine. Carol McLoughlin looks at the indications for administering diuretics,
      describes their modes of action and the possible side-effects.

PMID- 15497292
TI  - 'I feel strongly about supporting people'. Interview by Carolyn Scott.

PMID- 15497293
TI  - The power of persuasion.

PMID- 15497294
TI  - How can we work as a team?

PMID- 15497295
TI  - Increased anesthetic risk for patients with obesity and obstructive sleep apnea.

PMID- 15497296
TI  - Effects of a midazolam-ketamine admixture in human volunteers.
AB  - As the ideal sedative does not exist for all situations, we examined the effect
      of a midazolam-ketamine sedoanalgesic admixture in human volunteers. Ten ASA
      physical status I volunteers were administered loading doses of 0.07 mg/kg of
      midazolam followed by 0.7 mg/kg of ketamine. The same amount of midazolam and
      ketamine was then infused constantly over 1 hour via a 60 drops (gtts)/mL i.v.
      infusion set. Blood samples were analyzed for plasma catecholamine levels.
      Respiration rate and oxygen saturation did not alter significantly from baseline
      levels. Heart rate and systolic blood pressure remained stable with an increase
      of 15% in heart rate and 6% in systolic blood pressure only at 10 minutes
      following the bolus loading. Diastolic blood pressure did not alter significantly
      from baseline levels (P < .05). Plasma catecholamines levels remained stable
      except for an increase in epinephrine (38%) and norepinephrine (19%) 10 minutes
      following the bolus injections. Plasma dopamine levels remained unchanged. There
      were no cases of unpleasant dreaming, dysphoria, or emergence-type reactions.
      This combined nonnarcotic sedoanalgesic technique maintains spontaneous
      ventilation and stable cardiorespiratory parameters and may be considered as an
      alternative to traditional conscious sedation or general anesthesia.

PMID- 15497297
TI  - Anesthetic efficacy of the anterior middle superior alveolar (AMSA) injection.
AB  - The purpose of this prospective, randomized, blinded study was to determine the
      anesthetic efficacy of the anterior middle superior alveolar (AMSA) injection
      using the computer-assisted Wand Plus injection system versus a conventional
      syringe. The authors, using a crossover design, randomly administered in a blind
      manner 2 AMSA injections utilizing the computer-assisted injection system and a
      conventional syringe to 40 subjects during 2 separate appointments. A pulp tester
      was used to test for anesthesia, in 4-minute cycles for 60 minutes, of the
      central and lateral incisors, canine, and first and second premolars. Anesthesia
      was considered successful when 2 consecutive no responses (80 readings) with the
      pulp tester were obtained. For all teeth, except the central incisor, the use of
      the computer-assisted injection system was significantly (P < .05) more likely to
      result in pulpal anesthesia than the use of the conventional syringe technique.
      For the computer-assisted injection system, successful pulpal anesthesia ranged
      from 35 to 58%, and for the conventional syringe, successful pulpal anesthesia
      ranged from 20 to 42%. For both techniques, the onset of pulpal anesthesia was
      slow, and duration of pulpal anesthesia declined steadily over 60 minutes. We
      conclude that although the AMSA injection using the computer-assisted injection
      system was more successful than the conventional syringe technique, the rather
      modest to low success rates, slow onset, and declining duration of pulpal
      anesthesia over 60 minutes would not ensure predictable pulpal anesthesia from
      the second premolar to the central incisor.

PMID- 15497298
TI  - Dental fears, health status, and quality of life.
AB  - A total of 137 patients in a Hamburg dental fears clinic, a majority of them
      persons with dental phobia, were administered questionnaires regarding dental
      fears and health-related quality of life. Subjects also underwent a dental
      examination. Dental fears were shown to be associated with dental health
      problems. Women were more fearful than men, and younger persons were more fearful
      than older ones. Patients of lower social economic status had somewhat more
      dental health problems compared with more economically privileged persons. This
      study also shows, with the use of the SF-36, that dental fears are negatively
      related to quality of life, especially as measured in areas such as psychological
      well-being, vitality, and social functioning.

PMID- 15497299
TI  - Sedation in Japanese dental schools.
AB  - There is very little information about the practice of sedation in Japan. Despite
      the remarkable advances in dentistry, fear and anxiety continue to be significant
      deterrents for seeking dental services. Most dental procedures can fortunately be
      undertaken with the aid of sedation. A comprehensive survey of all the dental
      schools in Japan was carried out to determine what sedation practices were used
      in Japan. All 29 dental schools in Japan possessed a dedicated department of
      anesthesiology at the time of this survey. The survey attempted to determine the
      specific sedation methods (techniques, routes of administration, and agents used
      in sedation) as well as practices (monitoring, fasting, location, education, and
      fees involved in sedation). The results indicate that there was a broad range in
      sedation practices. The Japanese Dental Society of Anesthesiology may wish to
      examine the findings of this study and may wish to formulate guidelines
      appropriate for the practice of sedation in Japan. Others may also wish to
      compare their own practices with those of Japan.

PMID- 15497301
TI  - [Role for vasopressin in cardiopulmonary resuscitation].

PMID- 15497300
TI  - Anesthetic management of a child with congenital central hypoventilation syndrome
      (CCHS, Ondine's curse) for dental treatment.
AB  - Congenital Central Hypoventilation Syndrome (CCHS, also known as Ondine's Curse)
      is a rare syndrome characterized by apnea, cyanosis, and hypotonia. A 4-year-old,
      90-cm, 12-kg girl with CCHS, mental retardation (MR), and Hischsprung's disease
      (HD) was treated under general anesthesia. Intravenous drugs were not used, but
      sevoflurane, a volatile anesthetic, was used. As a result, the recovery time from
      the end of the operation to returning to the ward was very short, only 18
      minutes. There was no trouble during the perioperative period. We safely
      performed general anesthesia and dental treatment for a girl who had CCHS with HD
      and MR.

PMID- 15497302
TI  - [When individuals are protected from research and trials, who protects their
      rights to receive best care based on existing studies?].

PMID- 15497303
TI  - [Do we need a Finnish biobank? Availability of epidemiologic data should benefit
      everybody].

PMID- 15497304
TI  - [Schizophrenia as a consequence of genetic modifications affecting brain
      development and plasticity].

PMID- 15497306
TI  - [What does the past can predict about the future?].

PMID- 15497305
TI  - [Surprise, surprise--the correlation between legislation and behavior of people
      explains the increasing number of accidents due to driving under the influence of
      alcohol].

PMID- 15497307
TI  - [Cognitive deficits in depression].

PMID- 15497308
TI  - [Abnormal coagulation in critical care patients].

PMID- 15497309
TI  - [Coarctation of aorta].

PMID- 15497310
TI  - [The role of therapeutic drug monitoring--what to study and when?].

PMID- 15497311
TI  - [Empyema--increasingly common complication connected to pneumonia in children].

PMID- 15497312
TI  - [Maxillary sinusitis].

PMID- 15497313
TI  - [A three month headache].

PMID- 15497314
TI  - [The cost of rehabilitating patients with hearing disorders].

PMID- 15497315
TI  - [Is there any reason to withhold statins from high risk patients with coronary
      artery disease during surgery?].

PMID- 15497316
TI  - [Dyslipidemias].

PMID- 15497317
TI  - [Mycobacteria and tropical regions: from the environment to man].

PMID- 15497318
TI  - [Use of the mycobacteria genome to develop new vaccines and therapeutic targets].

PMID- 15497319
TI  - [Tuberculosis in Africa: epidemiology and control measures].

PMID- 15497320
TI  - [Aspects and management of tuberculosis in the Far East. Case of Cambodia].

PMID- 15497321
TI  - [Control of leprosy in the world in 2004. Current situation and perspectives].

PMID- 15497322
TI  - [Buruli ulcer: epidemiological, clinical and therapeutic aspects in the Ivory
      Coast].

PMID- 15497323
TI  - [Utility of molecular tools in diagnosis, treatment, and epidemiology of
      mycobacterial infections].

PMID- 15497324
TI  - [A riddle solved--why valerian-hops extract makes you drowsy].

PMID- 15497325
TI  - [A fungal substance against arteriosclerosis].

PMID- 15497326
TI  - [Flexibility in avoiding resistance].

PMID- 15497327
TI  - [Nuclear receptors--watchful mistrust of tamoxifen].

PMID- 15497328
TI  - [The history of estrogen].

PMID- 15497329
TI  - [Selective estrogen receptor modulators].

PMID- 15497330
TI  - [The pharmacology of estrogens].

PMID- 15497331
TI  - [The women's health initiative and more].

PMID- 15497332
TI  - [When is hormone therapy useful?].

PMID- 15497333
TI  - [What are phytoestrogens and phyto-SERMS].

PMID- 15497334
TI  - [Phytotherapy in menopausal symptoms].

PMID- 15497335
TI  - [Estrogens--drug preparations].

PMID- 15497336
TI  - [Hormone therapy: consultation with the pharmacist].

PMID- 15497344
TI  - HBO thrapy: beyond the bends.

PMID- 15497345
TI  - Pediatric poisoning!

PMID- 15497346
TI  - Patient information. Poison control: keeping your children safe.

PMID- 15497347
TI  - Help patients cope with fibromyalgia.

PMID- 15497348
TI  - Patient information. Fibromyalgia.

PMID- 15497349
TI  - A nurse's apology.

PMID- 15497350
TI  - Prostate disease.

PMID- 15497351
TI  - Why not pursue a sideline career?

PMID- 15497352
TI  - Servants or colleagues?

PMID- 15497353
TI  - Do you have reasonable access to new products?

PMID- 15497354
TI  - Adhesive restorative materials: a review.
AB  - 'Adhesive' restorative dentistry originated with the work of Buonocore in 1955 in
      bonding resin to etched enamel. Since then, adhesive materials and techniques
      have developed at a rapid rate. The first chemically adhesive material (zinc
      polycarboxylate cement) was marketed in the late 1960s, and glass-ionomer cements
      and dentine bonding agents have since become available. This review focuses on
      the latter two products. Glass-ionomer cements have a particular role in adhesive
      dentistry because of their reliable chemical adhesion to enamel and dentine, and
      because of their apparent ability to promote the remineralization of 'affected'
      dentine. Dentine bonding agents have undergone marked changes in presentation
      over the last 15 years, but all have an essentially similar bonding system, that
      of hybrid layer formation. However, the most recent systems have limited clinical
      data supporting their use.

PMID- 15497355
TI  - Microbiological evaluation of endodontic files after cleaning and steam
      sterilization procedures.
AB  - BACKGROUND: Infection control procedures are essential for modern dental practice
      and they are continually evolving to meet the dental profession's high standards.
      The present study evaluated the efficacy of two cleaning procedures to reduce
      bacterial numbers on endodontic files, and evaluated the effect of biological
      debris on the subsequent sterilization of files. METHODS: Stainless steel and
      nickel-titanium (NiTi) files were examined upon removal from the manufacturer's
      packaging, after instrumentation in root canals of human teeth inoculated with a
      broth containing two anaerobic species and one facultative anaerobic species of
      bacteria, and after instrumentation and cleaning with either an ultrasonic bath
      or a thermal disinfector. For each file, the bacterial numbers were quantified
      using routine microbiological techniques in an anaerobic chamber. RESULTS: No
      bacteria were detected from files direct from their packets. The size, taper and
      type of file did not affect the ability of either of the cleaning procedures to
      reduce bacterial numbers. However, an absence of bacteria was more likely when
      files were cleaned in the thermal disinfector. No bacteria were detected from
      files that were-subjected to steam sterilization irrespective of the type of
      prior cleaning procedure. CONCLUSIONS: Steam sterilization eliminated all
      bacteria from the endodontic files irrespective of the presence of biological
      debris. The majority of bacteria were eliminated from endodontic files after
      either ultrasonic cleaning or using a thermal disinfector.

PMID- 15497356
TI  - A SEM evaluation of debris removal from endodontic files after cleaning and steam
      sterilization procedures.
AB  - BACKGROUND: In recent times, it has been proposed to classify endodontic files as
      single-use items due to a perceived inability to adequately clean the
      instruments. The purpose of the present study was to quantify the surface debris
      on files removed from the manufacturer's packaging, and after cleaning using an
      ultrasonic bath or a thermal disinfector. METHODS: Stainless steel and rotary
      nickel-titanium files were examined after removal from the manufacturer's
      packaging, after instrumentation in broth-contaminated human teeth, and after
      various cleaning procedures. The cleaning procedures consisted of either a
      thermal disinfector cycle, ultrasonication with the files placed in a perforated
      container or ultrasonication with the files loosely placed in a beaker. The
      presence of manufacturing debris and biological debris was evaluated using
      scanning electron microscopy and quantified using image analysis software.
      RESULTS: The effectiveness of cleaning was not affected by variation in the size
      or taper of the files when an effective cleaning procedure was used. Cleaning the
      files in a thermal disinfector or by ultrasonication within a container did not
      consistently achieve complete removal of biological debris. Placing the files
      loosely in the ultrasonic bath achieved the most effective cleaning, an average
      of 98.33 per cent of the file surface area was freed of any biological debris.
      CONCLUSIONS: A conventional cleaning method is capable of effectively removing
      biological debris from endodontic files. The efficacy of ultrasonic cleaning was
      impaired when the files were placed within a perforated container.

PMID- 15497357
TI  - A baseline study of the demographics of the oral health workforce in rural and
      remote Western Australia.
AB  - BACKGROUND: A shortage of dental practitioners in Australia is predicted for the
      future, and the greatest effect of this will be felt in rural and remote areas.
      Strategies are needed to increase the recruitment and retention of dental
      practitioners in these areas. Part of this process is to assess the demographics
      of the oral health workforce. METHODS: A postal questionnaire survey was
      undertaken in 2002, that involved all registered dentists, therapists and
      hygienists in rural and remote Western Australia. RESULTS: Rural dentists are
      predominantly male, early middle aged, married, UWA trained, Australian born with
      one to two children. Rural dental therapists are predominantly female, in their
      mid-thirties, married, Australian born, trained in Western Australia, with two
      children. Male dentists worked slightly more hours per week than female dentists.
      The majority of the workforce does have access to email and the internet. Taking
      leave is a problem for most dentists because of difficulties in finding locums.
      CONCLUSIONS: The rural dental workforce capacity and demographic distribution
      need monitoring and analysis. This will determine the dental workforce's future
      ability to deliver the necessary services in rural and remote regions, where
      currently there is a dental workforce shortage.

PMID- 15497358
TI  - Bond strength of simplified-step adhesives to enamel prepared with two different
      diamond burs.
AB  - BACKGROUND: Self-etching primers are reported to produce considerable etching on
      flat enamel surfaces. However, little is known about the influence of different
      enamel surface textures. In this study the influence of grinding enamel on bond
      strength of two all-in-one and one two-step adhesives was investigated. METHODS:
      Resin composite was bonded to the ground enamel of extracted human third molars
      that was reduced 0.5 mm from the buccal or lingual surfaces using either regular-
      or superfine-grit diamond burs with each of the three adhesives. After 24 hours
      in 37 degrees C water, the specimens were sectioned into slabs of 0.7 mm
      thickness, trimmed to an hourglass configuration, and subjected to microtensile
      bond strength (MTBS) testing. RESULTS: For all adhesive systems, MTBS to enamel
      ground with a regular-grit diamond bur was not significantly different from that
      with a superfine-grit diamond bur. The etching patterns of these adhesives were
      partly varied according to the aggressiveness of the adhesives. CONCLUSION: The
      use of two different burs does not affect the tensile bond strength of the
      adhesives to enamel.

PMID- 15497359
TI  - Latex allergy in dentistry. Review and report of case presenting as a serious
      reaction to latex dental dam.
AB  - Latex allergy may have severe consequences including development of anaphylaxis.
      This report describes a patient who underwent a reaction to latex dental dam
      manifesting as erythema, facial swelling and mild airway compromise. Restorative
      procedures under latex dental dam were performed under local anaesthesia on two
      occasions resulting in reactions of increasing severity. Following the first
      event the cause of the reaction was undetermined, but attributed to a possible
      allergy to local anaesthetic, and managed with corticosteroids and
      antihistamines. On a subsequent occasion the swelling was more severe, associated
      with difficulty in swallowing and mild airway compromise, and was managed as
      previously with adrenaline also being required. Latex allergy was subsequently
      confirmed.

PMID- 15497360
TI  - Oral health of Aboriginal Australians.

PMID- 15497361
TI  - Assessing restored teeth with pulp and periapical diseases.

PMID- 15497362
TI  - Army Ranger casualty, attrition, and surgery rates for airborne operations in
      Afghanistan and Iraq.
AB  - INTRODUCTION: Although numerous articles have been published documenting
      parachute injuries, a search of the medical literature revealed none that detail
      casualty, attrition, and surgery rates for airborne operations conducted into
      actual combat. This study examines observed airborne casualty, attrition, and
      surgery rates in U.S. Army Rangers during combat operations in order to identify
      risk factors attributed to static-line parachute injuries and provide a
      comparison to estimated attrition rates. METHODS: Data were recorded on
      standardized manual casualty cards and tracking forms while treatment was
      provided during two missions into Afghanistan during Operation Enduring Freedom
      and two missions into Iraq during Operation Iraqi Freedom, and then consolidated
      onto an electronic database for further analysis. RESULTS: There were 4 airborne
      missions totaling 634 jumpers that resulted in 83 injuries sustained by 76
      Rangers (12%). Of those, 27 Rangers (4%) were unable to continue the mission and
      were subsequently evacuated. There were 11 Rangers (2%) who required surgery
      following evacuation. The overall observed attrition rate differed from the
      estimated rate (p = 0.04). Although observed attrition rates did not differ from
      estimations in Afghanistan (p = 0.75), attrition rates in Iraq were greater than
      estimated rates (p = 0.02) and observed rates in Afghanistan (p = 0.05).
      DISCUSSION: Many factors impact casualty, attrition, and injury patterns. Terrain
      and equipment load were notable associations analyzed in this study. CONCLUSIONS:
      Medical, logistical, and operational personnel can optimize support for airborne
      forces through improved estimation of casualty, attrition, and surgical rates.
      Risk factors associated with military parachuting can potentially provide further
      accuracy in estimating attrition and are recommended for integration into current
      models.

PMID- 15497363
TI  - Lower body positive and negative pressure alter thermal and hemodynamic responses
      after exercise.
AB  - INTRODUCTION: The purpose of this study was to determine the effect of upright
      lower body positive and negative pressure (LBPP/LBNP) application on the post
      exercise thermal response. It was hypothesized that the application of LBPP would
      decrease core temperature secondary to increases in skin blood flow (SkBF) and
      sweating, whereas the application of LBNP would maintain core temperature
      secondary to attenuated SkBF and sweating responses. METHODS: There were six
      subjects who randomly underwent each of the following treatments in the upright
      posture, separated by a minimum of 48 h: 1) +45 mmHg LBPP; 2) -20 mmHg LBNP; or
      3) no pressure for 45 min after performing 15 min of cycle ergometry exercise at
      70% of their VO2peak. Measurements included mean arterial pressure (MAP), heart
      rate (HR), cardiac output (Q), stroke volume (SV), total peripheral resistance
      (TPR), mean skin temperature (Tsk), mean heat flux, esophageal temperature (Tes),
      SkBF, and sweat rate. RESULTS: After the application of LBPP, we observed a
      significantly greater decrease in core temperature relative to the LBNP and
      control conditions (p < 0.001). This was accompanied by increases in SkBF,
      sweating, and heat flux (p < 0.05), all of which were higher than the LBNP and
      control conditions. Core temperature, SkBF, sweating, and heat flux in the LBNP
      and control conditions were not different from each other. LBPP promoted the
      restoration of hemodynamics while LBNP and control prolonged the post-exercise
      hemodynamic state. CONCLUSION: We conclude that during recovery from exercise in
      the upright seated posture, core temperature recovery is affected by compromised
      SkBF and sweating secondary to nonthermal cardiovascular influences.

PMID- 15497364
TI  - Centrifuge training increases presyncopal orthostatic tolerance in ambulatory
      men.
AB  - INTRODUCTION: Exposure to spaceflight or simulations of microgravity reduce human
      postflight orthostatic tolerance. Exercise training and volume loading can reduce
      associated losses of plasma volume and muscle strength, but are not successful in
      maintaining postflight orthostatic tolerance. A preliminary study (16) indicated
      that short bouts of artificial gravity (AG) training on a centrifuge could
      increase orthostatic tolerance in healthy, ambulatory volunteers. We tested the
      same AG protocol for its tolerance effect on 14 men who underwent a 3-wk exposure
      to Gz acceleration training on NASA-Ames' (Moffet Field, CA) human-powered
      centrifuge. METHODS: Subjects trained supine (head near the center of rotation)
      and in pairs (one subject rode passively while the other provided power to
      operate the 1.9-m centrifuge). The acceleration profile consisted of 7 min at 1
      Gz before alternating between 1 and 2.5 Gz at 2-min intervals for 28 min. Each
      subject's presyncopal orthostatic tolerance limit (to a combination of 70 degrees
      head-up tilt and increasing lower body negative pressure) was determined before
      and after training. RESULTS: There were no significant differences between
      training groups, but presyncopal orthostatic tolerance time was improved 17 +/-
      10% (p < 0.05) for the combined groups. Mechanisms associated with increased
      tolerance included: increased cardiac output (p < 0.04), stroke volume (p < 0.01)
      and low-frequency spectral power of arterial pressure (p < 0.006), and decreased
      arterial pressure (p < 0.05) and vascular resistance (p < 0.04). Artificial
      gravity training in this group of men appears to increase orthostatic tolerance
      through a combination of decreased vascular resistance and enhanced cardiac
      function.

PMID- 15497365
TI  - Altitude decompression sickness at 7620 m following prebreathe enhanced with
      exercise periods.
AB  - INTRODUCTION: Over 80% altitude decompression sickness (DCS) was reported during
      a 4-h exposure with mild exercise to 7620 m (25,000 ft) without prebreathe.
      Prebreathe for more than 1 h would be necessary to reduce the DCS risk below 40%.
      Use of a single period of exercise to enhance prebreathe effectiveness has been
      successfully tested and used during some U-2 operations. The current tests used
      multiple exercise sessions to enhance prebreathe (MEEP) as a means of improving
      denitrogenation efficiency. METHODS: Two MEEP profiles, 30 or 60 min, preceded 4
      h exposures to 7620 m with mild, upper-body exercise while breathing 100% oxygen.
      Resting prebreathe controls were from published studies at the same laboratory.
      Both MEEP profiles involved 10 min of strenuous dual-cycle ergometry (75% of
      maximal oxygen uptake) at the beginning of prebreathe. After a 15-min rest period
      during the 60-min prebreathe, an additional 5 min of strenuous ergometry was
      performed. Mild exercise was performed during 15 of the last 20 min of both
      prebreathe profiles. RESULTS: The 60-min MEEP resulted in 25% DCS and the 30-min
      MEEP 40% DCS (N.S.). The 25% incidence of DCS following the 60-min MEEP profile
      was significantly less than the 63% DCS following an equal-time, resting
      prebreathe control. Following the 30-min MEEP, DCS incidence was not greater than
      the incidence following a 60-min, resting prebreathe control. There was a lower
      incidence of venous gas emboli during the MEEP exposures than during resting
      control exposures. CONCLUSION: Denitrogenation with multiple periods of exercise
      provides a shorter alternative to resting prebreathe for reducing DCS risk during
      exposure to 7620 m.

PMID- 15497366
TI  - Acute caffeine intake before and after fatiguing exercise improves target
      shooting engagement time.
AB  - INTRODUCTION: Previous research has identified acute caffeine ingestion as an
      effective aid in counteracting the decline in vigilance experienced during sentry
      duty and sustained operations. However, further research is needed to clarify
      caffeine's effects under various stressors and additional operational conditions.
      The purpose of the present study was to examine the effect of caffeine on target
      detection and rifle marksmanship during simulated combat operations. METHODS:
      There were 12 reservists who ingested 5 mg x kg(-1) body mass of caffeine (C) or
      placebo (P) 1 h before beginning a 2.5-h loaded march and 1.0-h sandbag wall
      construction task. Following exercise, participants were given a re-dose of 2.5
      mg x kg(-1) body mass of C or P. An hour after ingestion, participants commenced
      a 2.5-h shooting session on a small arms simulator, which included friend-foe
      discrimination (FF) and vigilance (VIG) tasks. Marksmanship performance measures
      included engagement time (ET), the number of shots fired (NS), accuracy, and
      precision. RESULTS: C ingestion (initial and/or redose) did not affect shooting
      performance during the FF task. ET and NS improved during the VIG task with C
      ingestion (mean +/- SD of 2.82 +/- 0.27 s and 29.2 +/- 1.9 shots out of 30
      targets, respectively) compared with the P trial (3.00 +/- 0.26 s and 28.0 +/-
      3.0 shots; p < 0.05). CONCLUSION: Caffeine ingestion improves target detection
      and engagement speed during vigilance situations, but is not effective during
      more complex operations requiring higher levels of cognitive processing and fine
      motor control and coordination.

PMID- 15497367
TI  - Sopite symptoms in the optokinetic drum.
AB  - Sopite syndrome is a disturbance caused by motion characterized by drowsiness and
      mood changes that may occur without the classic symptoms of motion sickness.
      Because sopite symptoms are often subtle, it is important to assess for their
      presence, and to distinguish true sopite symptoms from changes in mood and
      drowsiness that are due to non-motion related factors such as fatigue and
      boredom. We compared sopite symptoms in the optokinetic drum (OKD) with symptoms
      in a control condition in which the drum's motion cues were removed. METHODS:
      There were 48 Introductory Psychology students who were randomly assigned to 1 of
      2 groups: the rotating stripes group (RS) sat inside a drum lined with black and
      white stripes. The drum rotated at 5 rpm. The control group (Ctrl) sat inside the
      same drum without stripes or rotation. All participants completed the Positive
      and Negative Affect Scale (PANAS), the Motion Sickness Assessment Questionnaire
      (MSAQ), and the Epworth Sleepiness Scale (ESS) at pre- and post-drum exposures.
      RESULTS: The RS, but not the Ctrl, showed increases on all four MSAQ subscales
      (gastric, peripheral, central, sopite). The groups showed equivalent decreases in
      positive and negative affect. These findings show that some sopite-related
      symptoms were due specifically to the motion stimuli, while others could be
      attributed to non-motion aspects of the experimental situation. DISCUSSION: The
      findings have implications for the use of control conditions in the study of
      sopite syndrome, and for methods of assessing the changes in mood and drowsiness
      that are the cardinal symptoms of sopite.

PMID- 15497368
TI  - Apnea-induced changes in time estimation and its relation to bradycardia.
AB  - INTRODUCTION: Both exercise and hypoxia affect human ability to estimate time, an
      alteration thought to be induced by changes in subjects' level of arousal. Apnea
      induces cardiovascular changes and a decrease in oxygen uptake that indicate
      changes in physiological arousal. We tested time estimation (TE) during brief
      periods of voluntary apnea. We hypothesized that there would be a relationship
      between TE and heart rate (HR), a physiological indicator of arousal. METHODS:
      Subjects were two different groups of seven triathletes. To measure TE, the
      target time interval (20 or 30 s) was demonstrated and the subject was then asked
      to reproduce it under various conditions. Experiment 1 required 1 min of breath
      holding while immersed in a pool at 31 degrees C. Experiment 2 was performed
      seated on a cycle ergometer in a laboratory and involved short periods of apnea
      at rest and during exercise. RESULTS: TE during apnea was significantly greater
      than baseline during both immersion and at rest on the cycle (+27% and +17%
      compared with their respective baselines). A significant linear negative
      correlation was demonstrated between TE and HR. Training in apnea during exercise
      had no effect on TE. DISCUSSION: Although this study revealed a relationship
      between TE and HR, our results should be interpreted with caution. Further
      studies are needed to confirm the relationship between HR and TE. A misperception
      of elapsed time may be a contributing factor in diving accidents which involve
      inexperienced breath-hold divers.

PMID- 15497370
TI  - EEG and ECG changes during selected flight sequences.
AB  - BACKGROUND: Mental workload has become a critical factor in the design and use of
      modern aircraft. Because of the complexity of the human-machine system, it is
      necessary to determine workload, fatigue, and level of performance using
      noninvasive electrophysiological measures. OBJECTIVE: Our objective was to
      identify the electrophysiological indicators of mental workload during piloting
      tasks. METHODS: Electroencephalographic (EEG) and electrocardiographic (ECG)
      activity was recorded during actual flight, with a profile planned to produce
      different levels of mental workload. RESULTS: In-flight EEG and ECG recordings
      enabled us to document mental workload levels. During active segments, delta and
      theta band activity increased (p < 0.05 or greater); results showed an increase
      of 22.5% for theta band activity during active flight segments compared with in
      flight rest periods. Inversely, alpha band activity diminished: the decrease
      between ground baseline and all flight sequences was 30% (p < 0.05 or greater).
      These variations were reversed during the in-flight rest sequences. Instrumental
      flight caused an increase in the theta and alpha frequency band activity in the
      parietal-occipital area (p < 0.05 or greater); the alpha/beta ratio also
      increased. Heart rate increased during the active segments and fell during the in
      flight rest periods. The mean difference between active segments and in-flight
      rest periods was of 8.89 bpm (i.e., an increase of 11.5%; p < 0.01). Heart rate
      was correlated to the EEG activity of the delta and beta bands in the central
      area (C3, Cz, C4, p < 0.05). CONCLUSIONS: The electrophysiological measures
      recorded provide useful indicators of the mental workload required by different
      flight sequences.

PMID- 15497369
TI  - Antioxidant supplementation does not attenuate oxidative stress at high altitude.
AB  - INTRODUCTION: Hypobaric hypoxia and heightened metabolic rate increase free
      radical production. PURPOSE: We tested the hypothesis that antioxidant
      supplementation would reduce oxidative stress associated with increased energy
      expenditure (negative energy balance) at high altitude (HA 4300 m). METHODS: For
      12 d at sea level (SL), 18 active men were fed a weight-stabilizing diet. Testing
      included fasting blood and 24-h urine samples to assess antioxidant status
      [plasma alpha-tocopherol, beta-carotene, lipid hydroperoxides (LPO), and urinary
      8-hydroxydeoxyguanosine (8-OHdG)] and a prolonged submaximal (55% Vo2peak)
      oxidative stress index test (OSI) to evaluate exercise-induced oxidative stress
      (plasma LPO, whole blood reduced and oxidized glutathione, glutathione
      peroxidase, and urinary 8-OHdG). Subjects were then matched and randomly assigned
      to either a placebo or antioxidant supplement group for a double-blinded trial.
      Supplementation (20,000 IU of beta-carotene, 400 IU alpha-tocopherol acetate, 500
      mg ascorbic acid, 100 microg selenium, and 30 mg zinc, or placebo) was begun 3 wk
      prior to and throughout a 14-d HA intervention. At HA, subjects' daily energy
      intake and expenditure were adjusted to achieve a caloric deficit of
      approximately 1400 kcal. Fasting blood and 24-h urine samples were collected
      throughout HA and the OSI test was repeated on HA day 1 and day 13. RESULTS:
      Resting LPO concentrations increased and urinary 8-OHdG concentrations decreased
      over HA with no effect of supplementation. Prolonged submaximal exercise was not
      associated with increased concentrations of oxidative stress markers at SL or HA.
      CONCLUSIONS: Antioxidant supplementation did not significantly affect markers of
      oxidative stress associated with increased energy expenditure at HA.

PMID- 15497371
TI  - Clockwise and counterclockwise rotating shifts: effects on temperature and
      neuroendocrine measures.
AB  - INTRODUCTION: Most researchers suggest that shift rotation in a clockwise (CW)
      direction produces less disruption of circadian rhythms than rotations in a
      counterclockwise (CCW) direction. This is based on extrapolation from quasi
      experimental studies of shift workers and research on the effects of jet lag that
      indicate that westward travel results in less disruption of circadian rhythms.
      METHODS: The effect of direction of rotation on cortisol, melatonin, and rectal
      temperature was examined in participants randomly assigned to either a CW (n =
      14) or CCW (n = 14) shift rotation. RESULTS: Results revealed lower amplitude
      [F(1,21) = 14.6, p < 0.05] and a delay of the acrophase [F(1,21) = 4.4, p < 0.05]
      in temperature for the CCW group. Sample time effects for cortisol and melatonin
      revealed normal circadian variation for both rotations, although melatonin levels
      on the midnight shift were clearly suppressed relative to baseline melatonin
      levels. DISCUSSION: The changes observed in the temperature rhythm for the CCW
      rotation may be related to adaptation or shift-work hardiness; however, it is
      unclear if these differences indicate beneficial or detrimental changes for the
      individual. The fact that there were no significant effects of rotation condition
      for cortisol or melatonin argues against a detrimental effect. These findings are
      bolstered by performance and sleep data, reported elsewhere from this study,
      indicating a lack of significant differences as a function of rotation condition.

PMID- 15497372
TI  - Predicted arterial oxygenation at commercial aircraft cabin altitudes.
AB  - INTRODUCTION: The degree of hypoxia manifested by airline passengers during
      flight is not well characterized. Statistical models to predict age-specific
      levels of Pao2 manifest at altitudes between sea level and 8000 ft (Pao2alt) are
      described. METHODS: The relationship between age and Pao2 at sea level (Pao2sl)
      and the relationship between Pao2alt, and Pao2sl, Pco2 at sea level (Pco2sl), and
      pulmonary health status were investigated using linear regression techniques to
      analyze previously published data. RESULTS: In persons with normal pulmonary
      health, the relationship between Pao2sl (mmHg) and age (yr) was Pao2sl = 105.9 -
      0.44 * age (R2 = 0.582, MSE = 25.314); Pco2sl (38.1 +/- 2.8 mmHg) was not related
      to age over the range 18-75 yr. In persons with chronic obstructive lung disease
      (COPD), neither Pao2sl (78.2 +/- 11.3 mmHg) nor Pco2sl (40.5 +/- 5.7 mmHg) were
      related to age (77.0 +/- 9.0 yrs).The relationship between PaO2alt and Pao2sl,
      Pco2sl and altitude (ft) was: Pao2alt = 1.59 + 0.98 * Pao2sl + 0.0031 * Alt -
      0.000061 * Pao2sl * Alt - 0.000065 * PCO(2)sl [corrected] * Alt + 0.000000092 *
      Alt2 (R2 = 0.932, MSE = 22.774). DISCUSSION: Pao2sl declines with age in persons
      with normal pulmonary health; Pco2sl remains constant. Neither vary with age in
      persons with COPD. Pao2alt can be estimated with acceptable precision from
      knowledge of Pao2sl, Pco2sl, and altitude. These models predict a substantial
      proportion of older passengers will manifest a Pao2alt at 8000 ft below the
      threshold at which supplemental oxygen is recommended.

PMID- 15497373
TI  - Acute cerebellar vertigo in a fighter pilot.
AB  - Vertigo is a frequently encountered complaint among aviators. This complaint is
      usually labyrinthine in origin. We present a case of a combat jet fighter pilot
      who experienced a vertiginous episode during flight that nearly resulted in a
      mishap. Work-up revealed a dissecting aneurysm of the posterior inferior
      cerebellar artery. Coiling of the aneurysm was performed. This case emphasizes
      the importance of performing a complete vestibular evaluation in aviators with
      acute vertigo. Since central nervous system causes may be responsible for
      vertiginous events, and when undiagnosed may result in a recurrence during
      flight, magnetic resonance scanning should be considered in those with no obvious
      peripheral cause for their vertigo.

PMID- 15497374
TI  - The contributions of Lavoisier, Carnot, and Mayer to understanding heat illness.
AB  - Although heat illness has been described throughout recorded history, an
      understanding of its pathophysiology was only achieved in the 20th century.
      Lavoisier, Carnot, and Mayer described fundamental concepts about thermodynamics
      in the late 18th and early 19th centuries that were crucial to the eventual
      understanding of heat illness. Lavoisier recognized that the human body was a
      heat engine. Carnot recognized that useful heat engines must dissipate heat.
      Mayer recognized that humans possess the capacity to regulate body heat. The
      fundamental contributions of Lavoisier, Carnot, and Mayer to the understanding of
      heat illness have gone largely unacknowledged.

PMID- 15497375
TI  - This month in Aerospace medicine history--October 2004.

PMID- 15497376
TI  - The resurgence of tactile display technologies.

PMID- 15497377
TI  - Physiologic control of rotary blood pumps: an in vitro study.
AB  - Rotary blood pumps (RBPs) are currently being used as a bridge to transplantation
      as well as for myocardial recovery and destination therapy for patients with
      heart failure. Physiologic control systems for RBPs that can automatically and
      autonomously adjust the pump flow to match the physiologic requirement of the
      patient are needed to reduce human intervention and error, while improving the
      quality of life. Physiologic control systems for RBPs should ensure adequate
      perfusion while avoiding inflow occlusion via left ventricular (LV) suction for
      varying clinical and physical activity conditions. For RBPs used as left
      ventricular assist devices (LVADs), we hypothesize that maintaining a constant
      average pressure difference between the pulmonary vein and the aorta (deltaPa)
      would give rise to a physiologically adequate perfusion while avoiding LV
      suction. Using a mock circulatory system, we tested the performance of the
      control strategy of maintaining a constant average deltaPa and compared it with
      the results obtained when a constant average pump pressure head (deltaP) and
      constant rpm are maintained. The comparison was made for normal, failing, and
      asystolic left heart during rest and at light exercise. The deltaPa was
      maintained at 95 +/- 1 mm Hg for all the scenarios. The results indicate that the
      deltaPa control strategy maintained or restored the total flow rate to that of
      the physiologically normal heart during rest (3.8 L/m) and light exercise (5.4
      L/m) conditions. The deltaPa approach adapted to changing exercise and clinical
      conditions better than the constant rpm and constant deltaP control strategies.
      The deltaPa control strategy requires the implantation of two pressure sensors,
      which may not be clinically feasible. Sensorless RBP control using the deltaPa
      algorithm, which can eliminate the failure prone pressure sensors, is being
      currently investigated.

PMID- 15497378
TI  - Transient and quasi-steady computational fluid dynamics study of a left
      ventricular assist device.
AB  - The HeartQuest continuous flow left ventricle assist device (LVAD) with a
      magnetically levitated impeller operates under highly transient flow conditions.
      Due to insertion of the in-flow cannula into the apex of the left ventricle, the
      inlet flow rate is transient because of ventricular contraction, and the pump's
      asymmetric circumferential configuration with five rotating blades forces blood
      intermittently through the pump to the great arteries. These two transient
      conditions correspond to time varying boundary conditions and transient
      rotational sliding interfaces in computational fluid dynamics (CFD). CFD was used
      to investigate the pump's performance under these dynamic flow conditions. A
      quasi-steady analysis was also conducted to evaluate the difference between the
      steady and transient analyses and demonstrate the significance of transient
      analysis, especially for transient rotational sliding interfaces transient
      simulations. This transient flow analysis can be applied generally in the design
      process of LVADs; it provides more reliable fluid forces and moments on the
      impeller for successful design of the magnetic suspension system and motor.

PMID- 15497379
TI  - Effects of turbulent stresses upon mechanical hemolysis: experimental and
      computational analysis.
AB  - Experimental and computational studies were performed to elucidate the role of
      turbulent stresses in mechanical blood damage (hemolysis). A suspension of bovine
      red blood cells (RBC) was driven through a closed circulating loop by a
      centrifugal pump. A small capillary tube (inner diameter 1 mm and length 70 mm)
      was incorporated into the circulating loop via tapered connectors. The suspension
      of RBCs was diluted with saline to achieve an asymptotic apparent viscosity of
      2.0 +/- 0.1 cP at 23 degrees C to produce turbulent flow at nominal flow rate and
      pressure. To study laminar flow at the identical wall shear stresses in the same
      capillary tube, the apparent viscosity of the RBC suspension was increased to 6.3
      +/- 0.1 cP (at 23 degrees C) by addition of Dextran-40. Using various
      combinations of driving pressure and Dextran mediated adjustments in dynamic
      viscosity Reynolds numbers ranging from 300-5,000 were generated, and rates of
      hemolysis were measured. Pilot studies were performed to verify that the
      suspension media did not affect mechanical fragility of the RBCs. The results of
      these bench studies demonstrated that, at the same wall shear stress in a
      capillary tube, the level of hemolysis was significantly greater (p < 0.05) for
      turbulent flow as compared with laminar flow. This confirmed that turbulent
      stresses contribute strongly to blood mechanical trauma. Numerical predictions of
      hemolysis obtained by computational fluid dynamic modeling were in good agreement
      with these experimental data.

PMID- 15497380
TI  - Extensive coagulation monitoring in patients after implantation of the MicroMed
      Debakey continuous flow axial pump.
AB  - Ventricular assist device (VAD) implantation is associated with impaired primary
      hemostasis and thromboembolic complications. Recently, a new generation of
      implantable continuous flow axial pumps was introduced into clinical application.
      To study the potential thrombogenic properties of this type of pump, we applied
      extensive platelet monitoring was applied. In our institution, 13 patients
      received the MicroMed DeBakey VAD as a bridge to transplantation. Routine
      coagulation tests (platelet count, activated partial thromboplastin time,
      prothrombin time, antithrombin III activity) and platelet function tests (whole
      blood aggregometry, thrombelastography, flow cytometry) were performed. No
      clinically relevant thromboembolic events were detected. No correlation was found
      between global function tests, platelet aggregation, and thrombelastography. No
      correlation was detected between platelet activation and hemolysis parameters.
      Platelet aggregation and coagulation index were significantly suppressed early
      after operation. A subsequent phase of hyper-aggregability, starting around day
      6, suggested the initiation of antiaggregation therapy. Platelet activation
      markers were upregulated in the postoperative period but were returned to
      preoperative levels after initiation of aspirin. In contrast to routine
      coagulation monitoring, platelet function tests reflect in detail the coagulation
      status of blood pump recipients and the efficiency of antiaggregation therapy.
      Aspirin and dipyridamole therapy in addition to oral anticoagulation using
      phenprocoumon may contribute to platelet function and clot mechanics restoration
      and is, therefore, recommended for patients after VAD implantation.

PMID- 15497381
TI  - Effects of left ventricular assist device support and outflow graft location upon
      aortic blood flow.
AB  - Although continuous flow (CFVAD) and pulsatile (PVAD) ventricular assist devices
      (VADs) are being clinically used, their effects upon aortic blood flow as a
      measure of overall blood distribution remain unclear. The objective of this study
      was to compare the effects of CFVAD and PVAD support for ascending (AscA) and
      descending (DA) aorta outflow cannulation upon mean aortic blood flow and
      waveform morphology. Six experiments were conducted in a normal, acute calf
      model, in which an inflow cannula was implanted in the left ventricle apex and
      outflow cannulae were anastomosed to both the AscA and DA. Flow probes were
      placed around the pulmonary artery, pump outflow, brachiocephalic trunk, and
      aorta proximal and distal to the DA outflow. For each acute experiment, calves
      received randomly selected levels of VAD support (0-100% of cardiac output) and
      pump failure (VAD off and outflow cannula unclamped) for each of four randomly
      selected test conditions: (1) PVAD and AscA, (2) PVAD and DA, (3) CFVAD and AscA,
      and (4) CFVAD and DA. Regardless of pump type or support level, proximal and
      distal aorta mean flows were lower (p < 0.05) for DA compared with the AscA. No
      differences in mean aortic flows between pump types at either outflow graft
      location were discerned. Differences in morphologic features of blood flow
      waveforms between PVAD and CFVAD were observed. During simulated pump failure,
      retrograde aortic blood flow in both the aortic arch and DA was observed. Partial
      ventricular suction was also observed during the greatest levels of CFVAD support
      and suggested pronounced effects upon both the right and left ventricle.
      Collectively, these findings imply that VAD outflow location may have an
      important role in patient response and recovery. Investigation of the long-term
      pathophysiologic responses to pump type and outflow location is ongoing.

PMID- 15497382
TI  - Safety and biocompatibility of the Myosplint system--a passive implantable device
      that alters ventricular geometry for the treatment of heart failure.
AB  - A passive implantable device developed for the treatment of heart failure, the
      Myosplint System, has demonstrated therapeutic efficacy in a canine model of
      pacing induced heart failure. The current study sought to demonstrate chronic
      device safety and biocompatibility, in vivo, in a normal porcine model. Two
      devices were implanted into each normal, beating heart of 6 juvenile and 15 adult
      pigs without cardiopulmonary bypass. Animals survived 90 (juvenile and adult) or
      180 days (adult only). Serial hematologic and biochemical profiles were evaluated
      in each pig during the study period. A comprehensive necropsy study was performed
      in each pig to evaluate device stability, healing response, thromboembolism,
      hemorrhage, and intravascular hemolysis related to the Myosplint system. Six
      adult animals died from infectious disease (four) or perioperative (two)
      complications unrelated to device design or function and were excluded from the
      final analysis. No clinical, biochemical or pathologic evidence of significant,
      device related adverse events was observed in surviving animals. The chronic
      myocardial healing response appeared normal at term, and all devices maintained
      their structural integrity throughout the study. The Myosplint system was easily
      implanted in beating hearts and was rapidly incorporated into host tissues
      without clinically significant morbidity in this porcine model.

PMID- 15497383
TI  - Biventricular support with the Jarvik 2000 ventricular assist device in a calf
      model of pulmonary hypertension.
AB  - The Jarvik 2000 ventricular assist device (VAD) is clinically efficacious for
      treating end-stage left ventricular failure. Because simultaneous right
      ventricular support is also occasionally necessary, we developed a biventricular
      Jarvik 2000 technique and tested it in a calf model. One VAD was implanted in the
      left ventricle with outflow-graft anastomosis to the descending aorta. The other
      VAD was implanted in the right ventricle with outflow-graft anastomosis to the
      pulmonary artery. Throughout the 30 day study, hemodynamic values were
      continuously monitored. On day 30, both pumps were evaluated at different speeds,
      under various hemodynamic conditions. By gradually occluding the pulmonary artery
      proximally or distally, we simulated varying degrees of high pulmonary vascular
      resistance, right ventricular hypertension, global heart failure, or ventricular
      fibrillation. The two VADs maintained biventricular support even during pulmonary
      artery occlusion and ventricular fibrillation, yielding a cardiac output of 3-11
      L/min, left ventricular end-diastolic pressure of 11-24 mm Hg, and central venous
      pressure of 9-25 mm Hg. End-organ function was unimpaired, and no major adverse
      events occurred. The dual VADs offered safe, effective biventricular assistance
      in the calf. Additional studies are needed to assess the effects of lowered pulse
      pressure upon the pulmonary circulation and to develop a single pump speed
      controller.

PMID- 15497384
TI  - The relationship between antioxidant supplements and oxidative stress in renal
      transplant recipients: a review.
AB  - Renal transplant recipients (RTRs) have elevated oxidative stress and a high
      incidence of cardiovascular morbidity and mortality. Although recent studies do
      not support the use of antioxidant supplements as a cardioprotectant in the
      general population, evidence suggests that RTRs may represent individuals that
      would benefit from this therapy. RTRs have elevated oxidative stress probably
      caused by the immunosuppressive therapy, and although only a small number of
      studies have examined the effects of antioxidant supplementation in these
      patients, most have reported beneficial findings. This review discusses these
      studies along with the rationale for the use of antioxidant supplements in RTRs
      and a call for more research to investigate this important topic.

PMID- 15497385
TI  - Hemorrhagic shock resuscitation with an artificial oxygen carrier, hemoglobin
      vesicle, maintains intestinal perfusion and suppresses the increase in plasma
      tumor necrosis factor-alpha.
AB  - It is known that damage to the intestinal mucosa followed by systemic
      inflammatory response is one of the leading causes of shock related morbidity and
      mortality. In this study, we examined the ability of an artificial oxygen carrier
      hemoglobin vesicle (HbV) to sustain systemic and intestinal perfusion during
      hemorrhagic shock. In rabbits, hemorrhagic shock (40% of the estimated blood
      volume) was resuscitated with 5% albumin (alb group), HbV suspended in 5% albumin
      (HbValb group), or washed red blood cells suspended in 5% albumin (RBCalb group).
      Plasma tumor necrosis factor (TNF)-alpha level was measured in rats under the
      same experimental protocol. No significant intergroup differences were seen in
      systemic hemodynamics. In contrast, parameters of intestinal perfusion
      significantly deteriorated in the alb group but were equally well sustained in
      the HbValb and RBCalb groups. Also, a significant increase in plasma TNF-alpha
      level was seen in the alb group but not in the RBCalb or HbValb groups. These
      results indicate the proficient oxygen transporting capability of HbV and its
      potential efficacy in shock resuscitation.

PMID- 15497386
TI  - Use of omentum as an in vivo cell culture system in tissue engineering.
AB  - Many modifications of in vitro culture techniques have been applied to promote
      tissue formation, resulting in limitations. Because the omentum is composed of
      lobes of adipose tissue with abundant blood vessels and has been used for organ
      reconstruction, we used the omentum as an in vivo culture system to promote
      cellular proliferation upon the scaffold. Two kinds of autogenous cells, oral
      epithelial cells and rib chondrocytes, obtained from canine were isolated and
      then seeded on porous poly-lactic-glycolic acid scaffolds of a pre-determined
      shape and size. Comparison was performed in two groups. In Group 1, cell-polymer
      constructs were cultured in vitro for 2 weeks, and in group 2, cell-polymer
      constructs were cultured in vitro for 1 week following the same protocol as group
      1 but were then implanted into the omentum of same canines for the next week. We
      performed histologic analysis of tissue formation between the two groups. In
      group 1, seeded cells were presented spatially along the porous polymer surface
      only. However, in group 2, the cell-polymer constructs maintained their original
      dimensions and showed formation of a multicell layered structure with abundant
      blood vessels. We concluded that the use of the omentum as an in vivo culture
      medium offers possibilities as an efficient and effective method for tissue
      engineering with greater vascularization and more consistent cell spacing
      throughout the construct.

PMID- 15497387
TI  - Initial assessment of a tissue engineered stomach derived from syngeneic donors
      in a rat model.
AB  - The objective of this study is to assess the feasibility of creating a tissue
      engineered stomach using isolated stomach epithelium organoid unit from syngeneic
      adult donors and a biodegradable polymer scaffold in a rat model. Despite recent
      advances in reconstruction techniques, total gastrectomy is still accompanied by
      various complications. As an alternative treatment, a tissue engineered stomach
      that replaces the mechanical and metabolic functions of a normal stomach is
      proposed. Stomach epithelium organoid units were isolated from syngeneic adult
      rats and seeded onto biodegradable polymers. These constructs were implanted into
      the omenta of recipient adult rats. All constructs were harvested for histologic
      and immunohistochemical examination at designated time points. Cyst-like
      structures were formed that showed the development of vascularized tissue with a
      neomucosa. Immunohistochemical staining for alpha-actin smooth muscle, gastric
      mucin, and proton pump indicated the presence of a smooth muscle layer and
      gastric epithelium, as well as the existence of parietal cells of the stomach
      mucosa, respectively. Epithelium derived stomach organoid units seeded on
      biodegradable polymers were transplanted in donor rats and have been shown to
      vascularize, survive, and regenerate into complex tissue resembling a native
      stomach. These initial results are encouraging, and studies are currently
      underway to further assess this approach.

PMID- 15497388
TI  - Blood damage related to cardiopulmonary bypass: in vivo and in vitro comparison
      of two different centrifugal pumps.
AB  - Cardiopulmonary bypass (CPB) induces hemolysis and the activation of the
      inflammatory and coagulation systems. Several components of the CPB equipment may
      contribute to such phenomenon. We tested the effects of two differently designed
      centrifugal pumps (Bio-Pump, Medtronic and Revolution, Cobe) on several markers
      of hemolysis, coagulation, and inflammation: plasma free hemoglobin,prothrombin
      fragment 1.2, platelet factor 4, and P-selectin. Twenty patients requiring
      coronary artery bypass grafting were randomized to undergo CPB with one of the
      study centrifugal pumps, and 10 experiments (5 for each pump) were performed with
      a closed loop circuit to assess pumps' performances over 6 circulation hours
      using human blood. CPB induced a significant elevation of all the tested markers.
      Neither in the in vivo nor in the in vitro study were significant differences
      observed between the groups. Because the Revolution centrifugal pump, which was
      recently designed and distributed, produced results comparable with those
      obtained with the BioPump, it should be considered as safe as the Bio-Pump to
      perform clinical CPB.

PMID- 15497389
TI  - Biostability of Thoralon left ventricular assist device blood pumping sacs after
      long-term clinical use.
AB  - The purpose of this paper is to investigate the biostability of Thoralon
      polyurethane blood pumping sacs that have been used for up to 14 months in the
      Thoratec ventricular assist device (VAD) in human subjects. Thoralon is a
      proprietary polyetherurethaneurea (PEUU) blended with siloxane based surface
      modifying additive (SMA). Samples of Thoralon blood sacs that were used in
      Thoratec LVAD pumps for 53, 171, 336, and 434 days were taken from three distinct
      regions identified as high flex, medium flex, and low flex for physicochemical
      analysis. Explanted samples exhibited a slight but not significant increase in
      physical properties. The molecular weight of the blood sacs had also increased
      significantly in all blood sacs regardless of duration of use. SEM images did not
      indicate any cracking, pitting, or surface erosion; however, in a small area of
      the high flex region of the 336 day sac some biofilm was seen. The Attenuated
      Total Reflectance Fourier Transform Infra Red Spectroscopy (ATR-FTIR) analysis
      showed no significant reduction of surface ether content. The surface chemistry
      analyzed using Electron Spectroscopy for Chemical Analysis (ESCA) also indicated
      no significant change compared with control. These results confirm the
      biostability of Thoralon for long-term clinical applications in the Thoratec VAD.

PMID- 15497390
TI  - Total liquid ventilation: dynamic airway pressure and the development of
      expiratory flow limitation.
AB  - Expiratory flow limitation occurs during total liquid ventilation (TLV), and is
      characterized by the sudden development of excessively negative intratracheal
      pressures without increases in flow. The purpose of this study was to identify a
      dynamic signal for the servoregulation of expiratory flow (Ve), by determining
      the range of dynamic intratracheal pressures [P(T)], which mark the onset of flow
      limitation during liquid expiration, where choke occurs at the critical pressure
      (Pc). The lungs of rabbits were filled with perflurocarbon to an end-inspiratory
      lung volume (EILV) of 20, 30, or 40cc/kg and connected to a piston driven liquid
      ventilator, which removed perfluorocarbon at a rate (Vs) of 2.5, 5.0, or 7.5
      ml/s. Nine animals per EILV group were used (27 animals total), and within each
      EILV group each (Vs) was used three times. P(T) and (Ve) (T) were measured at the
      tracheostomy tube, and dP/dT was calculated from P(T). Pc was determined within
      each EILV/(Vs) group by examining the average dP/dT curve for the first
      significant change from baseline. Pc ranged from -6.02 +/- 1.83 to -9.02 +/- 3.2
      mm Hg. In general, the higher the EILV, the more negative the Pc. We conclude
      that Pc during TLV varies within a limited range in rabbits. These data may be
      used to maximize expired volume during TLV by sequentially tapering flow rates as
      this critical range of pressures is approached.

PMID- 15497391
TI  - Evaluation of plasma resistant hollow fiber membranes for artificial lungs.
AB  - Hollow fiber membranes (HFMs) used in artificial lungs (oxygenators) undergo
      plasma leakage (or wetting) in which blood plasma slowly fills the pores of the
      fiber wall, plasma leaks into gas pathways, and overall gas exchange decreases.
      To overcome this problem plasma resistant fibers are being developed that are
      skinned asymmetric or composite symmetric versions of microporous oxygenator
      fibers. This report evaluates several candidate plasma resistant HFMs in terms of
      their gas permeance and plasma resistance as measured in a surfactant wet out
      test. Five candidate fibers were compared with each other and with a control
      fiber. CO2 and O2 gas permeance (in ml/s/cm2/cm Hg) in the plasma resistant
      fibers ranged from 3.15E-04 to 1.71E-03 and 3.40E-04 to 1.08E-03, respectively,
      compared with 1.62E-02 and 1.77E-02 for the control fiber. Maximum dye bleed
      through for the plasma resistant fibers in the forced wet out test were
      significantly less than for the control fiber. CO2 gas permeance of a plasma
      resistant fiber imposes the greatest constraint upon artificial lung design for
      sufficient gas exchange. However, our results suggest sufficient plasma
      resistance can be achieved using special skinned and composite HFMs while
      maintaining an acceptable CO2 gas permeance for a broad range of artificial lung
      applications.

PMID- 15497392
TI  - The influence of a nonlinear resistance element upon in vitro aortic pressure
      tracings and aortic valve motions.
AB  - In vitro testing of biological heart valves requires pressure and flow waveforms
      closely simulating natural conditions, which are mainly influenced by the
      characteristics of the vascular system. Simulation of the arterial function in
      artificial circulations was mostly performed by the useful Windkessel model but
      sometimes failed by generating inadequate systolic pressures. The integration of
      a novel nonlinear resistance element may improve the Windkessel function. Native
      porcine aortic valves were studied in a mock circulation with a novel nonlinear
      resistance element combined with the Windkessel compared with an aperture plate
      resistance. Pressure and flow measurements were performed at varying heart rates
      and stroke volumes and analyzed in the time and frequency domain. Aortic valve
      motions were evaluated using high speed video recording. With the classical
      afterload configuration including an aperture plate resistance, the pressure
      tracings showed a nonphysiologic decrease of pressure during systole after early
      peak pressure. By integration of the novel nonlinear resistance, peak systolic
      pressure occured later, peak pressure was higher, and the pressure waveform was
      more physiologically shaped. Leaflet motions of the aortic valves were less
      oscillatory and compared well with in vivo characteristics. In conclusion, a
      novel nonlinear resistance element in a mock circulation has the potential to
      provide more physiologic aortic pressure waveforms as influencing aortic valve
      dynamics and thus may be a helpful tool for investigation of biological heart
      valves.

PMID- 15497393
TI  - Liver function during extracorporeal whole liver perfusion in a pig model of
      acute ischemic liver failure.
AB  - The shortage of livers for transplant has renewed interest in the potential of
      temporary liver support such as extra corporeal whole liver perfusion. In an
      ischemic induced liver failure model we perfused an extra corporeal liver through
      only a portal vein and assessed the function of this ex vivo liver by using
      hepatic tests to estimate elimination as well as synthesis capacities. Acute
      liver failure was performed in five control pigs by a hepatic devascularization
      associated to an end to side portocaval shunt. In a treated group, 5 to 6 h after
      this hepatic devascularization, animals were connected to an extra corporeal
      liver perfused via the portal vein with blood withdrawn from the ischemic liver
      animal from its portal vein. Devascularization of the liver induced an increase
      in liver enzymes and ammonia, a drop in the ratio of branched chain amino acids
      to aromatic amino acids, and a decrease in blood urea and indocyanine green and
      galactose clearances. In treated animals, urea, amino acid ratio, and clearances
      increased after the ex vivo liver perfusion. In this group, mean bile production
      and mean liver oxygen consumption were 13.7 +/- 3.6 ml/h and 16.1 +/- 7.7 ml/min,
      respectively. In an acute ischemic liver failure pig model, an extra corporeal
      whole liver perfusion demonstrated detoxification properties as well as synthesis
      capacities.

PMID- 15497394
TI  - Left ventricular and myocardial perfusion responses to volume unloading and
      afterload reduction in a computer simulation.
AB  - Ventricular assist devices (VADs) have been used successfully as a bridge to
      transplant in heart failure patients by unloading ventricular volume and
      restoring the circulation. In a few cases, patients have been successfully weaned
      from these devices after myocardial recovery. To promote myocardial recovery and
      alleviate the demand for donor organs, we are developing an artificial
      vasculature device (AVD) that is designed to allow the heart to fill to its
      normal volume but eject against a lower afterload. Using this approach, the heart
      ejects its stroke volume (SV) into an AVD anastomosed to the aortic arch, which
      has been programmed to produce any desired afterload condition defined by an
      input impedance profile. During diastole, the AVD returns this SV to the aorta,
      providing counterpulsation. Dynamic computer models of each of the assist devices
      (AVD, continuous, and pulsatile flow pumps) were developed and coupled to a model
      of the cardiovascular system. Computer simulations of these assist techniques
      were conducted to predict physiologic responses. Hemodynamic parameters,
      ventricular pressure-volume loops, and vascular impedance characteristics were
      calculated with AVD, continuous VAD, and asynchronous pulsatile VAD support for a
      range of clinical cardiac conditions (normal, failing, and recovering left
      ventricle). These simulation results indicate that the AVD may provide better
      coronary perfusion, as well as lower vascular resistance and elastance seen by
      the native heart during ejection compared with continuous and pulsatile VAD. Our
      working hypothesis is that by controlling afterload using the AVD approach,
      ventricular cannulation can be eliminated, myocardial perfusion improved,
      myocardial compliance and resistance restored, and effective weaning protocols
      developed that promote myocardial recovery.

PMID- 15497395
TI  - Successful treatment of refractory bleeding after bridging from acute to chronic
      left ventricular assist device support with recombinant activated factor VII.
AB  - Cardiac surgery often is associated with a significant disruption of the
      coagulation system, particularly in high risk patients such as those undergoing
      placement of ventricular assist devices. This type of severe coagulopathy can
      lead to life threatening bleeding that can require massive transfusions to
      restore hemostasis. Recently, recombinant activated factor VII (rFVlla) has been
      +used as an alternative to massive transfusion for the treatment of refractory
      bleeding in several patient populations, including cardiac surgery patients. In
      the case reported here, the patient's risk was compounded by multiple operations
      in a short period of time and circulatory collapse that was initially managed
      with a shortterm left ventricular assist device. After multiple failed attempts
      at weaning the patient from circulatory assistance, he was taken back to the
      operating room for conversion to a chronic, implantable device. This procedure
      was complicated by a severe coagulopathy secondary to a myriad of factors
      commonly encountered after the use of cardiopulmonary bypass. The administration
      of rFVlla resulted in a rapid cessation of bleeding without thrombotic
      complications. This is the first case reported involving an acute to chronic
      bridge patient. Despite the anecdotal success of rFVlla, further clinical
      research is needed to establish both the safety and economic feasibility of this
      agent.

PMID- 15497396
TI  - Use of A-Med Paraflow System for right heart support after heart transplantation.

PMID- 15497397
TI  - Development of ectopic roots from abortive nodule primordia.
AB  - The symbiotic phenotype of five Tn5-induced mutants of Rhizobium etli affected in
      different anabolic pathways (namely, gluconeogenesis and biosynthesis of lysine,
      purine, or pyrimidine) was analyzed. These mutants induced, on the root of
      Phaseolus vulgaris, a normal early sequence of morphogenetics events, including
      root hair deformation and development of nodule primordia. Later on, however,
      from the resulting root outgrowths, instead of nodules, one or more ectopic roots
      (spaced closely related and agravitropic) emerged. Therefore, this group of
      mutant was collectively called "root inducer" (RIND). It was observed that the
      RIND-induced infection threads aborted early inside the invaded root hair, and
      that the resulting abortive nodules lack induction of late nodulin genes.
      Moreover, experiments performed using a conditional mutant (a methionine
      requiring invader) revealed that bacterial invasion plays a key role in the
      maintenance of the program of nodule development and, in particular, in the
      differentiation of the most specific symbiotic tissue of globose nodules, the
      central tissue. These data indicate that, in P. vulgaris, the nodule primordium
      is a root-specified pro-meristematic tissue.

PMID- 15497398
TI  - Patterns of gene expression upon infection of soybean plants by Phytophthora
      sojae.
AB  - To investigate patterns of gene expression in soybean (Glycine max) and
      Phytophthora sojae during an infection time course, we constructed a 4,896-gene
      microarray of host and pathogen cDNA transcripts. Analysis of rRNA from soybean
      and P. sojae was used to estimate the ratio of host and pathogen RNA present in
      mixed samples. Large changes in this ratio occurred between 12 and 24 h after
      infection, reflecting the rapid growth and proliferation of the pathogen within
      host tissues. From the microarray analysis, soybean genes that were identified as
      strongly upregulated during infection included those encoding enzymes of
      phytoalexin biosynthesis and defense and pathogenesis-related proteins.
      Expression of these genes generally peaked at 24 h after infection. Selected
      lipoxygenases and peroxidases were among the most strongly downregulated soybean
      genes during the course of infection. The number of pathogen genes expressed
      during infection reached a maximum at 24 h. The results show that it is possible
      to use a single microarray to simultaneously probe gene expression in two
      interacting organisms. The patterns of gene expression we observed in soybean and
      P. sojae support the hypothesis that the pathogen transits from biotrophy to
      necrotrophy between 12 and 24 h after infection.

PMID- 15497399
TI  - Transcriptome profiling in root nodules and arbuscular mycorrhiza identifies a
      collection of novel genes induced during Medicago truncatula root endosymbioses.
AB  - Transcriptome profiling based on cDNA array hybridizations and in silico
      screening was used to identify Medicago truncatula genes induced in both root
      nodules and arbuscular mycorrhiza (AM). By array hybridizations, we detected
      several hundred genes that were upregulated in the root nodule and the AM
      symbiosis, respectively, with a total of 75 genes being induced during both
      interactions. The second approach based on in silico data mining yielded several
      hundred additional candidate genes with a predicted symbiosis-enhanced
      expression. A subset of the genes identified by either expression profiling tool
      was subjected to quantitative real-time reverse-transcription polymerase chain
      reaction for a verification of their symbiosis-induced expression. That way,
      induction in root nodules and AM was confirmed for 26 genes, most of them being
      reported as symbiosis-induced for the first time. In addition to delivering a
      number of novel symbiosis-induced genes, our approach identified several genes
      that were induced in only one of the two root endosymbioses. The spatial
      expression patterns of two symbiosis-induced genes encoding an annexin and a beta
      tubulin were characterized in transgenic roots using promoter-reporter gene
      fusions.

PMID- 15497400
TI  - Nitrogen fixation in wheat provided by Klebsiella pneumoniae 342.
AB  - In this report, all of the criteria necessary for the demonstration of nitrogen
      fixation in wheat (Triticum aestivum L.), the world's most important crop, are
      shown upon inoculation with a nitrogen-fixing bacterium, Klebsiella pneumoniae
      342 (Kp342). Kp342 relieved nitrogen (N) deficiency symptoms and increased total
      N and N concentration in the plant. Nitrogen fixation was confirmed by 15N
      isotope dilution in the plant tissue and in a plant product, chlorophyll. All of
      these observations were in contrast to uninoculated plants, plants inoculated
      with a nitrogen-fixing mutant of Kp342, and plants inoculated with dead Kp342
      cells. Nitrogenase reductase was produced by Kp342 in the intercellular space of
      the root cortex. Wild-type Kp342 and the nifH mutant colonized the interior of
      wheat roots in equal numbers on a fresh weight basis. The nitrogen fixation
      phenotype described here was specific to cv. Trenton. Inoculation of cvs. Russ or
      Stoa with Kp342 resulted in no relief of nitrogen deficiency symptoms.

PMID- 15497401
TI  - Enhancer trapping identifies TRI, an Arabidopsis gene up-regulated by pathogen
      infection.
AB  - Enhancer trap Arabidopsis thaliana plants were screened for genes up-regulated by
      virus infection. The plants carried T-DNA insertions comprising a minimal -60-bp
      Cauliflower mosaic virus 35S promoter fused to the beta-glucuronidase (GUS)
      reporter gene. Approximately 12,000 plants were assayed for GUS activity before
      and after rub-inoculation with Tobacco rattle virus (TRV) tagged with the green
      fluorescent protein (GFP). One plant and its progeny consistently showed
      upregulation of GUS activity in response to TRV-GFP infection, indicating that a
      virus-responsive enhancer element was "tagged" by the T-DNA in this line. Other
      viruses, bacteria, and oomycetes, but not wounding, up-regulated GUS activity in
      the enhancer trap line, indicating that the response was not specific to TRV-GFP
      infection. A pathogen-inducible, alternatively spliced gene was identified, which
      we have termed TRI for TRV-induced gene. A pathogen-responsive element was
      localized to a 1.1-kb region upstream of the T-DNA insertion, and two different
      cis-acting elements, both implicated in defense responses, were found in the
      sequence upstream of TRI. Sequence analyses revealed that TRI is similar to
      ACRE169, a gene that is up-regulated in Cf-9-expressing tobacco when treated with
      Avr-9, the Cladosporium fulvum elicitor of the Cf-9 resistance response.

PMID- 15497402
TI  - Impact of temperature on in planta expression of genes involved in synthesis of
      the Pseudomonas syringae phytotoxin coronatine.
AB  - Coronatine (COR) is a chlorosis-inducing phytotoxin produced by the plant
      pathogenic bacterium Pseudomonas syringae. Confocal laser scanning microscopy was
      used to investigate in vitro and in planta expression of COR genes by two model
      organisms, P. syringae pv. glycinea PG4180, a pathogen of soybean, and P syringae
      pv. tomato DC3000, a pathogen of tomato and crucifers. Previously, it was shown
      in vitro that the cma operon involved in COR synthesis in PG4180 is expressed in
      a temperature-dependent manner, with maximal rates at 18 degrees C and low
      activity at 28 degrees C. However, nothing was known about the influence of
      temperature on the expression of COR biosynthetic genes in planta. Therefore,
      transcriptional fusions of the PG4180 and DC3000 cma promoter regions to a
      promoterless egfp gene were constructed and expressed in both P. syringae
      strains. The fluorescence patterns in response to temperature during growth of a
      strain in vitro were consistent with its COR production and the cma transcript
      abundance as revealed by RNA dot blot hybridization. Quantification of
      fluorescence indicated that cma promoter activity was dependent on the genetic
      background of the host strain. Expression of cma::egfp in PG4180 was temperature
      dependent in minimal medium as well as inside the plant tissue. In contrast,
      transcription of the cma operon was not significantly affected by temperature in
      DC3000. However, cells of DC3000 harboring the cma::egfp fusions showed higher
      levels of fluorescence when recovered from infected host plants compared with
      cells grown in minimal medium. These results indicate that the signals for
      induction of COR biosynthesis differ significantly in PG4180 and DC3000.

PMID- 15497403
TI  - Expression patterns of defense-related genes in different types of arbuscular
      mycorrhizal development in wild-type and mycorrhiza-defective mutant tomato.
AB  - The expression of defense-related genes was analyzed in the interactions of six
      arbuscular mycorrhizal (AM) fungi with the roots of wild-type tomato
      (Lycopersicon esculentum Mill.) cv. 76R and of the near-isogenic mycorrhiza
      defective mutant rmc. Depending on the fungal species, wild-type tomato forms
      both major morphological AM types, Arum and Paris. The mutant rmc blocks the
      penetration of the root surface or invasion of the root cortex by most species of
      AM fungi, but one fungus has been shown to develop normal mycorrhizas. In the
      wild-type tomato, accumulation of mRNA representing a number of defense-related
      genes was low in Arum-type interactions, consistent with findings for this AM
      morphotype in other plant species. In contrast, Paris-type colonization,
      particularly by members of the family Gigasporaceae, was accompanied by a
      substantial transient increase in expression of some defense-related genes.
      However, the extent of root colonization did not differ significantly in the two
      wild-type AM morphotypes, suggesting that accumulation of defense gene products
      per se does not limit mycorrhiza development. In the mutant, interactions in
      which the fungus failed to penetrate the root lacked significant accumulation of
      defense gene mRNAs. However, phenotypes in which the fungus penetrated epidermal
      or hypodermal cells were associated with an enhanced and more prolonged gene
      expression. These results are discussed in relation to the mechanisms that may
      underlie the specificity of the interactions between AM fungi and the rmc mutant.

PMID- 15497404
TI  - Molecular population genetic analysis differentiates two virulence mechanisms of
      the fungal avirulence gene NIP1.
AB  - Deletion or alteration of an avirulence gene are two mechanisms that allow
      pathogens to escape recognition mediated by the corresponding resistance gene in
      the host. We studied these two mechanisms for the NIP1 avirulence gene in field
      populations of the fungal barley pathogen Rhynchosporium secalis. The product of
      the avirulence gene, NIP1, causes leaf necrosis and elicits a defense response on
      plants with the Rrs1 resistance gene. A high NIP1 deletion frequency (45%) was
      found among 614 isolates from different geographic populations on four
      continents. NIP1 was also sequenced for 196 isolates, to identify DNA
      polymorphisms and corresponding NIP1 types. Positive diversifying selection was
      found to act on NIP1. A total of 14 NIP1 types were found, 11 of which had not
      been described previously. The virulence of the NIP1 types was tested on Rrs1 and
      rrs1 barley lines. Isolates carrying three of these types were virulent on the
      Rrs1 cultivar. One type each was found in California, Western Europe, and Jordan.
      Additionally, a field experiment with one pair of near-isogenic lines was
      conducted to study the selection pressure imposed by Rrs1 on field populations of
      R. secalis. Deletion of NIP1 was the only mechanism used to infect the Rrs1
      cultivar in the field experiment. In this first comprehensive study on the
      population genetics of a fungal avirulence gene, virulence to Rrs1 in R. secalis
      was commonly achieved through deletion of the NIP1 avirulence gene but rarely
      also through point mutations in NIP1.

PMID- 15497405
TI  - Tagging quantitative trait loci for maturity-corrected late blight resistance in
      tetraploid potato with PCR-based candidate gene markers.
AB  - Late blight caused by the oomycete Phytophthora infestans is the economically
      most important and destructive disease in potato cultivation. Quantitative
      resistance to late blight available in tetraploid cultivars is correlated with
      late maturity in temperate climates, which is an undesirable characteristic. A
      total of 30 DNA-based markers known to be linked to loci for pathogen resistance
      in diploid potato were selected and tested as polymerase chain reaction-based
      markers for linkage with quantitative trait loci (QTL) for late blight resistance
      and plant maturity in two half-sib families of tetraploid potatoes. Most markers
      originated from within or were physically closely linked to candidate genes for
      quantitative resistance factors. The families were repeatedly evaluated in the
      field for quantitative resistance to late blight and maturity. Resistance was
      corrected for the maturity effect. Nine of eleven different map segments tagged
      by the markers harbored QTL affecting maturity-corrected resistance. Interactions
      were found between unlinked resistance QTL, providing testable strategies for
      marker-assisted selection in tetraploid potato. Based on the linkage observed
      between QTL for resistance and plant maturity and based on the genetic
      interactions observed between candidate genes tagging resistance QTL, we discuss
      models for the molecular basis of quantitative resistance and maturity.

PMID- 15497406
TI  - Tobacco genes induced by the bacterial effector protein AvrPto.
AB  - The type III effector protein AvrPto acts as a virulence factor in susceptible
      plants lacking a cognate resistance gene but triggers hypersensitive response and
      disease resistance in tomato plants carrying the Pto gene or in tobacco plants
      carrying an unknown resistance gene. To assist the characterization of cellular
      responses caused by AvrPto in the plant, a pathogen-free system was adopted to
      isolate genes up-regulated 12 h after induced expression of AvrPto. By using
      subtraction cloning and transgenic tobacco plants expressing avrPto as a
      transgene, we isolated 125 nonredundant cDNA clones that represent avrPto
      response genes (ARG). In addition to genes that are known to be induced by Pto
      avrPto recognition, a number of new genes were also isolated. Most of ARG showed
      a specific induction in tobacco plants challenged with incompatible or nonhost
      pathogens. The use of an avrPto mutant that selectively eliminated the avrPto
      recognition in tobacco demonstrated that the ARG were induced in a highly
      specific manner by the avirulence, instead of the virulence activity of avrPto.

PMID- 15497407
TI  - Candidate defense genes as predictors of quantitative blast resistance in rice.
AB  - Although quantitative trait loci (QTL) underpin many desirable agronomic traits,
      their incorporation into crop plants through marker-assisted selection is limited
      by the low predictive value of markers on phenotypic performance. Here we used
      candidate defense response (DR) genes to dissect quantitative resistance in rice
      using recombinant inbred (RI) and advanced backcross (BC) populations derived
      from a blast-resistant cultivar, Sanhuangzhan 2 (SHZ-2). Based on DNA profiles of
      DR genes, RI lines were clustered into two groups corresponding to level of
      resistance. Five DR genes, encoding putative oxalate oxidase, dehydrin, PR-1,
      chitinase, and 14-3-3 protein, accounted for 30.0, 23.0, 15.8, 6.7, and 5.5% of
      diseased leaf area (DLA) variation, respectively. Together, they accounted for
      60.3% of the DLA variation and co-localized with resistance QTL identified by
      interval mapping. Average phenotypic contributions of oxalate oxidase, dehydrin,
      PR-1, chitinase, and 14-3-3 protein in BC lines were 26.1, 19.0, 18.0, 11.5, and
      10.6%, respectively, across environments. Advanced BC lines with four to five
      effective DR genes showed enhanced resistance under high disease pressure in
      field tests. Our results demonstrate that the use of natural variation in a few
      candidate genes can solve a long-standing problem in rice production and has the
      potential to address other problems involving complex traits.

PMID- 15497408
TI  - Flavonoids, NodD1, NodD2, and nod-box NB15 modulate expression of the y4wEFG
      locus that is required for indole-3-acetic acid synthesis in Rhizobium sp. strain
      NGR234.
AB  - Flavonoids secreted by host plants activate, in conjunction with the
      transcriptional activator NodD, nod gene expression of rhizobia resulting in the
      synthesis of Nod factors, which trigger nodule organogenesis. Interestingly,
      addition of inducing flavonoids also stimulates the production of the
      phytohormone indole-3-acetic acid (IAA) in several rhizobia. Here, the molecular
      basis of IAA synthesis in Rhizobium sp. NGR234 was investigated. Mass
      spectrometric analysis of culture supernatants indicated that NGR234 is capable
      of synthesizing IAA via three different pathways. The production of IAA is
      increased strongly by exposure of NGR234 to daidzein in a NodD1-, NodD2-, and
      SyrM2-dependent manner. This suggests that the y4wEFG locus that is downstream of
      nod-box NB15 encodes proteins involved in IAA synthesis. Knockout mutations in
      y4wE and y4wF abolished flavonoid-inducible IAA synthesis and a functional y4wF
      was required for constitutive IAA production. The promoter activity of NB15 and
      IAA production both were enhanced by introduction of a multicopy plasmid carrying
      nodD2 into NGR234. Surprisingly, the y4wE mutant still nodulated Vigna
      unguiculata and Tephrosia vogelii, although the nodules contained less IAA and
      IAA conjugates than those formed by the wild-type bacterium.

PMID- 15497409
TI  - Overexpression of NtERF5, a new member of the tobacco ethylene response
      transcription factor family enhances resistance to tobacco mosaic virus.
AB  - A new member of the tobacco (Nicotiana tabacum) AP2/ERF (ethylene response
      factor) transcription factor family, designated NtERF5, has been isolated by
      yeast one-hybrid screening. In vitro, recombinant NtERF5 protein weakly binds GCC
      box cis-elements, which mediate pathogen-regulated transcription of several PR
      (pathogenesis related) genes. NtERF5 transcription is transiently activated by
      wounding, by infection with the bacterial pathogen Pseudomonas syringae, as well
      as by inoculation with Tobacco mosaic virus (TMV). In contrast, NtERF5
      transcription is not enhanced after application of salicylic acid, jasmonic acid,
      or ethylene. Constitutive overexpression of NtERF5 (ERF5-Oex) under control of
      the 35S promoter results in no visible alterations in plant growth or enhanced
      resistance to Pseudomonas infection. Furthermore, no constitutive expression of
      PR genes has been observed. In contrast, ERF5-Oex plants show enhanced resistance
      to TMV with reference to reduced size of local hypersensitive-response lesions
      and impaired systemic spread of the virus. Since, in TMV-infected ERF5-Oex
      plants, the viral RNA accumulates only up to 10 to 30% of the wild-type level, we
      suggest that NtERF5-regulated gene expression is controlling resistance to viral
      propagation. Previous research has demonstrated that overexpression of ERF genes
      enhances resistance to bacterial and fungal pathogens. Here, we provide further
      evidence that resistance to viral infection can be engineered by overexpression
      of ERF transcription factors.

PMID- 15497410
TI  - Estimating visible through near-infrared spectral reflectance from a sensor
      radiance spectrum.
AB  - We show that surface spectral reflectance can be separated from illumination
      effects in visible through near-infrared (350 nm-1740 nm) hyperspectral data by
      using only the information in a single radiance spectrum. The separation method
      exploits the fact that reflectance and illumination spectra typically lie in
      distinct subspaces. We present a comparison of a linear and a nonlinear algorithm
      for the separation. These algorithms compute an estimate of the spectral
      reflectance up to a scaling factor. In addition, we present an iterative method
      that is used to determine the starting point for the nonlinear algorithm. We also
      develop a method for selecting the dimension of the reflectance and illumination
      subspaces that is appropriate for material identification applications. The
      accuracy of the separation methods is quantified by application to noisy visible
      through near-infrared spectral data with a database of 107 materials and 3000
      illumination spectra. The utility of the separation method for material
      identification is demonstrated with the same database. The results show that
      accurate reflectance recovery and material identification is possible by use of
      visible through near-infrared spectral data over the outdoor environmental
      conditions represented in this data set.

PMID- 15497411
TI  - Aberration reduction by multiple relays of an incoherent image.
AB  - Consider a generally aberrated one-dimensional (1D) optical pupil P illuminated
      by quasi-monochromatic light of mean wavelength lambda. In past work it was found
      that, if the pupil's intensity point-spread function (psf) is multiply convolved
      with itself, as in an imaging relay system, and then ideally (stigmatically)
      demagnified, the resulting psf s(x) approaches a fixed Cauchy form s(x) = deltax(
      pi2x2 + deltax2)(-1), which is independent of the aberrations of the pupil. Here
      deltax is the Nyquist sampling interval given by deltax = lambdaf/2 with f the
      f/number of the pupil. This Cauchy form for this intensity psf s(x) also
      manifestly lacks sidelobes. The overall questions that we examine are how far do
      these effects carry over to the case of a circular, two-dimensional (2D) pupil,
      and to what extent do practical imaging considerations compromise the theoretical
      results? It is found that, in the presence of spherical aberration of all orders,
      the resulting theoretical psf of a large number of self-convolutions approaches a
      "circular" Cauchy form, S(r) = 2deltar[pi2r2 + (4deltar/pi)2](-3/2), where deltar
      is the Nyquist sampling interval lambdaf/2 with f the f/number of the (now)
      circular pupil. Thus, for these aberrations the 1D effect does carry over to the
      2D case: The output psf does not depend on the aberrations and completely lacks
      sidelobes. However, when all aberrations are generally present, the output psf
      s(r, theta) does depend on the aberrations, although its azimuthal average over
      theta still preserves the circular Cauchy form, as a superposition of Cauchy
      functions. Imaging requirements for achieving these ideal effects are briefly
      discussed as well as probability laws for photons that are implied by the above
      mentioned PSF's s(x) and S(r). Real-time super resolution is not attained, since
      the stigmatic imaging demanded of the demagnification step requires the use of a
      larger-apertured lens. Rather, the approach achieves significant aberration
      suppression.

PMID- 15497412
TI  - MISTRAL: a myopic edge-preserving image restoration method, with application to
      astronomical adaptive-optics-corrected long-exposure images.
AB  - Deconvolution is a necessary tool for the exploitation of a number of imaging
      instruments. We describe a deconvolution method developed in a Bayesian framework
      in the context of imaging through turbulence with adaptive optics. This method
      uses a noise model that accounts for both photonic and detector noises. It
      additionally contains a regularization term that is appropriate for objects that
      are a mix of sharp edges and smooth areas. Finally, it reckons with an imperfect
      knowledge of the point-spread function (PSF) by estimating the PSF jointly with
      the object under soft constraints rather than blindly (i.e., without
      constraints). These constraints are designed to embody our knowledge of the PSF.
      The implementation of this method is called MISTRAL. It is validated by
      simulations, and its effectiveness is illustrated by deconvolution results on
      experimental data taken on various adaptive optics systems and telescopes. Some
      of these deconvolutions have already been used to derive published astrophysical
      interpretations.

PMID- 15497413
TI  - Factor graph methods for three-dimensional shape reconstruction as applied to
      LIDAR imaging.
AB  - Two methods based on factor graphs for reconstructing the three-dimensional (3D)
      shape of an object from a series of two-dimensional images are presented. First,
      a factor graph model is developed for image segmentation to obtain silhouettes
      from raw images; the shape-from-silhouette technique is then applied to yield the
      3D reconstruction of the object. The second method presented is a direct 3D
      reconstruction of the object using a factor graph model for the voxels of the
      reconstruction. While both methods should be applicable to a variety of input
      data types, they will be developed and demonstrated for a particular application
      involving the LIDAR imaging of a submerged target. Results from simulations and
      from real LIDAR data are shown that detail the performance of the methods.

PMID- 15497414
TI  - Transverse or axial superresolution with radial birefringent filter.
AB  - The superresolution technique is well known for its ability to compress the
      central diffraction spot to a size that is smaller than the Airy diffraction
      spot. The radial birefringent filter, which consists of two parallel polarizers
      and a rotationally symmetric birefringent element, is introduced into the
      superresolution technology, and the pupil function of it is deduced. It is shown
      that such a filter can be adapted either for transverse superresolution or for
      axial superresolution simply by changing the angle between either of the two
      polarizers and the radial birefringent element. At the same time the
      superresolution parameters are discussed. The filter is relatively simple in
      construction as it requires no phase changes, and low-cost replication is
      possible.

PMID- 15497415
TI  - Chromatic compensation of broadband light diffraction: ABCD-matrix approach.
AB  - Compensation of chromatic dispersion for the optical implementation of
      mathematical transformations has proved to be an important tool in the design of
      new optical methods for full-color signal processing. A novel approach for
      designing dispersion-compensated, broadband optical transformers, both Fourier
      and Fresnel, based on the collimated Fresnel number is introduced. In a second
      stage, the above framework is fully exploited to achieve the optical
      implementation of the fractional Fourier transform (FRT) of any diffracting
      screen with broadband illumination. Moreover, we demonstrate that the amount of
      shift variance of the dispersion-compensated FRT can be tuned continuously from
      the spatial domain, which is totally space variant, to the spectral domain, which
      is totally space invariant, with the chromatic correction remaining unaltered.

PMID- 15497416
TI  - Reduction of computation time for crossed-grating problems: a group-theoretic
      approach.
AB  - A systematic approach based on group theory is established to deal with
      diffraction problems of crossed gratings by exploiting symmetries. With this
      approach, a problem in an asymmetrical incident mounting can be decomposed into a
      superposition of several symmetrical basis problems so that the computation
      efficiency is improved effectively. This methodology offers a convenient and
      succinct way to treat all possible symmetry cases by following only several
      mechanical steps instead of intricate mathematical considerations or physical
      intuition. It is also general, applicable to both scalar-wave and vector-wave
      problems and in principle can be easily adapted to any numerical method. A
      numerical example is presented to show its application and effectiveness.

PMID- 15497417
TI  - Diffraction corrections in radiometry: spectral and total power and asymptotic
      properties.
AB  - Wolf's result for integrated flux in the case of diffraction by a circular lens
      or aperture in the scalar, paraxial Fresnel approximation is considered anew.
      Compact integral formulas for pertinent infinite sums are derived, and the
      result's generalizations to extended sources and Planckian sources and asymptotic
      aspects at small wavelength and high temperature are all considered.
      Simplification of calculations for an actual absolute radiometer is demonstrated.

PMID- 15497418
TI  - Coherence and polarization of electromagnetic beams modulated by random phase
      screens and their changes on propagation in free space.
AB  - The spectral degree of coherence and of polarization of some model
      electromagnetic beams modulated by a polarization-dependent phase-modulating
      device, such as a liquid-crystal spatial light modulator, acting as a random
      phase screen are examined on the basis of the recent theory formulated in terms
      of the 2 x 2 cross-spectral density matrix of the beam. The phase-modulating
      device is assumed to have strong polarization dependence that modulates only one
      of the orthogonal components of the electric vector, and the phase of the phase
      modulating device is assumed to be a random function of position imitating a
      random phase screen and is assumed to obey Gaussian statistics with zero mean.
      The propagation of the modulated beam is also examined to show how the spectral
      degrees of coherence and of polarization of the beam change on propagation, even
      in free space. The results are illustrated by numerical examples.

PMID- 15497419
TI  - Variable-coherence tomography for inverse scattering problems.
AB  - We propose a technique for determining the pair-correlation function of a quasi
      homogeneous medium. The method uses the variation of the spatial-coherence
      properties of the incident beam to generate two separate volumes of coherence
      where the field is correlated. Using this specially prepared beam, we reconstruct
      experimentally the correlation function of a scattering potential by recording
      the scattered intensity in only one direction.

PMID- 15497420
TI  - Partially coherent vectorial nonparaxial beams.
AB  - Generalized vectorial Rayleigh-Sommerfeld diffraction integrals are developed for
      the cross-spectral-density matrices of spatially partially coherent beams. Using
      the Gaussian Schell-model (GSM) beam as an example, we derive the expressions for
      the propagation of cross-spectral-density matrices and intensity of partially
      coherent vectorial nonparaxial beams, and the corresponding far-field asymptotic
      forms, beyond the paraxial approximation. The propagation of the vectorial
      nonparaxial GSM beams are evaluated and analyzed. It is shown that a 3 x 3 cross
      spectral-density matrix or a vector theory is required for the exact description
      of nonparaxial GSM beams.

PMID- 15497421
TI  - Revised Kubelka-Munk theory. I. Theory and application.
AB  - Using a statistical analysis of light propagation in media, we propose a revision
      to Kubelka-Munk (K-M) theory by taking into account the effect of scattering on
      the path length of light propagation (path variation). This leads to new
      relationships between the K-M scattering S and absorbing K coefficients and the
      intrinsic scattering s and absorbing a coefficients of a material that indicate
      that the S and K coefficients depend non-linearly on both a and s. The additivity
      law that bridges K-M S and K coefficients of a composite medium, such as dye
      dispersed paper (dyed paper) and those of its material components (dye and
      paper), is also revised. It is further shown that experimental findings on dyed
      paper that the original K-M theory failed to explain can be clearly understood
      and accommodated by the new K-M theoretical framework (two-flux approach).
      Numerical simulations with the revised theory on model ink, paper, and dyed paper
      have been carried out.

PMID- 15497422
TI  - Revised Kubelka-Munk theory. II. Unified framework for homogeneous and
      inhomogeneous optical media.
AB  - We extend the applicability of the recently revised Kubelka-Munk (K-M) theory to
      inhomogeneous optical media by treating inhomogeneous ink penetration of the
      substrate. We propose a method for describing light propagation in either
      homogeneous or inhomogeneous layers using series representations for the K-M
      scattering and absorption coefficients as well as for intensities of the upward
      and downward light streams. The conventional and matrix expressions for spectral
      reflectance and transmittance values of optically homogeneous media in the K-M
      theory are shown to be special cases of the present framework. Three types of ink
      distribution-homogeneous, linear, and exponential-have been studied. Simulations
      of spectral reflectance predict a depression of reflectance peaks and reduction
      of absorption bands characteristic of hue shifts and significant reduction of
      saturation and, in turn, color gamut.

PMID- 15497424
TI  - Modeling turbulent wave-front phase as a fractional Brownian motion: a new
      approach.
AB  - We introduce a new, general formalism to model the turbulent wave-front phase by
      using fractional Brownian motion processes. Moreover, it extends results to non
      Kolmogorov turbulence. In particular, generalized expressions for the Strehl
      ratio and the angle-of-arrival variance are obtained. These are dependent on the
      dynamic state of the turbulence.

PMID- 15497423
TI  - Light scattering by multiple red blood cells.
AB  - The interaction of light with multiple red blood cells was systematically
      investigated by the finite-difference time-domain method (FDTD). The simulations
      showed that the lateral multiple scattering between red blood cells is very weak
      and that the polarization has an almost insignificant influence on the
      distribution of the scattered light. The numerical results of the FDTD method
      were compared with the results from the Rytov approximation and the discrete
      dipole approximation (DDA). The agreement with the DDA was excellent.

PMID- 15497425
TI  - Iterative transform algorithm for the computation of optimal beams.
AB  - The problem of maximizing the integrated-weighted intensity of a transmitted beam
      in a receiver plane is equivalent to the problem of finding the largest
      eigenvalue's eigenfunction for a particular Hermitian operator. Application of
      the power method for the determination of this eigenfunction, along with its
      associated eigen-value, results in an iterative transform algorithm that can be
      applied to arbitrary apertures, nonnegative windows, and propagation media. The
      computational complexity of each iteration of this algorithm is equivalent to the
      numerical propagation of an arbitrary beam through the transmission medium.

PMID- 15497426
TI  - A class of solution-invariant transformations of cost functions for minimum cost
      flow phase unwrapping.
AB  - Phase unwrapping (PU) represents an important step in synthetic aperture radar
      interferometry (InSAR) and other interferometric applications. Among the
      different PU methods, the so called branch-cut approaches play an important role.
      In 1996 M. Costantini [Proceedings of the Fringe '96 Workshop ERS SAR
      Interferometry (European Space Agency, Munich, 1996), pp. 261-272] proposed to
      transform the problem of correctly placing branch cuts into a minimum cost flow
      (MCF) problem. The crucial point of this new approach is to generate cost
      functions that represent the a priori knowledge necessary for PU. Since cost
      functions are derived from measured data, they are random variables. This leads
      to the question of MCF solution stability: How much can the cost functions be
      varied without changing the cheapest flow that represents the correct branch
      cuts? This question is partially answered: The existence of a whole linear
      subspace in the space of cost functions is shown; this subspace contains all cost
      differences by which a cost function can be changed without changing the cost
      difference between any two flows that are discharging any residue configuration.
      These cost differences are called strictly stable cost differences. For
      quadrangular nonclosed networks (the most important type of MCF networks for
      interferometric purposes) a complete classification of strictly stable cost
      differences is presented. Further, the role of the well-known class of node
      potentials in the framework of strictly stable cost differences is investigated,
      and information on the vector-space structure representing the MCF environment is
      provided.

PMID- 15497427
TI  - Modal analysis of astronomical bolometric interferometers.
AB  - A procedure is described for modeling the behavior of astronomical bolometric
      interferometers. The scheme is based on the notion of eigenfields. The input and
      output eigenfields are those field distributions on the sky and at the detector
      to which the individual telescopes of an interferometer can couple. Eigenfields
      are more fundamental than eigenmodes and provide, regardless of optical
      configuration, an orthogonal basis for propagating the second-order statistical
      properties of a field from a source through the telescopes, through the beam
      combiners, and onto the detectors. With our scheme, it is possible to calculate
      the power coupled into coherent, partially coherent, and incoherent imaging
      arrays and to include the spatially distributed noise sources of the telescopes
      themselves.

PMID- 15497428
TI  - Fringing-field effect in liquid-crystal beam-steering devices: an approximate
      analytical model.
AB  - An approximate analytical model was developed that links the fringing-field
      broadening of the phase profile of a liquid-crystal (LC) beam-steering device,
      and the resulting diffraction efficiency, to the physical parameters of the
      device including the cell thickness as well as the dielectric, optical, and
      geometrical constants of the device. The analysis includes a full solution of the
      Laplace equation for the LC device in which the broadening of the initial voltage
      profile into an effective voltage-drop profile, due to the fringing-field effect,
      is derived. It is shown that within the linear approximation used, the broadening
      of the phase profile is identical to the broadening of the effective voltage
      profile in the presence of the fringing field. On the basis of this model, the
      resulting broadening kernel of the phase profile is found to be proportional to
      the LC cell thickness. These results are found to be in an excellent agreement
      with high-precision computer simulations performed on the LC beam-steering
      structure, thereby validating this approximate linear model.

PMID- 15497429
TI  - Reflectivity of buried slab waveguides.
AB  - The scattering properties of an abruptly ended buried slab waveguide for both TE
      and TM modes are examined by an improved iteration technique that is based on the
      integral equation method with "accelerating" parameters. The waveguide is
      considered a symmetrical slab, for which the weakly guiding conditions are
      invalid, and it is embedded in a different dielectric material. The tangential
      electric field distribution on the terminal plane, the reflection coefficient of
      the first TE and TM guided modes, and the far-field radiation pattern are
      computed. Numerical results are presented for several ended waveguides, while
      special attention is given to the far-field radiation pattern rotation and the
      terminal field distributions.

PMID- 15497430
TI  - Achromatic angle-insensitive infrared quarter-wave retarder based on total
      internal reflection at the Si-SiO2 interface.
AB  - An achromatic infrared (lambda = 1.2-4 microm), Si-prism quarter-wave retarder
      (QWR) is described that uses total internal reflection at a buried Si-SiO2
      interface at an angle of incidence phi near 33 degrees, where deltaDelta/deltaphi
      = 0. The retardance delta deviates from 90 degrees by < +/- 2 degrees within a
      field of view of +/- 10 degrees (in air) over the entire bandwidth. Because the
      SiO2 layer at the base of the prism is optically thick, this QWR is unaffected by
      environmental contamination.

PMID- 15497431
TI  - Discrete-dipole approximation with polarizabilities that account for both finite
      wavelength and target geometry.
AB  - The discrete-dipole approximation (DDA) is a powerful method for calculating
      absorption and scattering by targets that have sizes smaller than or comparable
      with the wavelength of the incident radiation. We present a new prescription-the
      surface-corrected-lattice-dispersion relation (SCLDR)--for assigning the dipole
      polarizabilities while taking into account both target geometry and finite
      wavelength. We test the SCLDR in DDA calculations for spherical and ellipsoidal
      targets and show that for a fixed number of dipoles, the SCLDR prescription
      results in increased accuracy in the calculated cross sections for absorption and
      scattering. We discuss extension of the SCLDR prescription to irregular targets.

PMID- 15497432
TI  - Nonparaxial propagation of spirally polarized optical beams.
AB  - The free-propagation features of light beams whose transverse electric field
      lines are logarithmic spirals (namely, spirally polarized beams) are investigated
      in both the paraxial and the nonparaxial regime. The complete propagated electric
      field is considered, and some general properties are obtained regardless of the
      specific transverse distribution. Simple and significant analytical results are
      obtained when the transverse intensity profile is chosen as that pertinent to an
      axially symmetric Laguerre-Gaussian beam of order 1 (namely, spirally polarized
      donut beams). In particular, it is found that for such beams, the propagated
      longitudinal electric field can be expressed as a simple superposition of elegant
      Laguerre-Gaussian beams. Numerical results are presented for different values of
      the beam parameters and are compared with recently obtained experimental results.

PMID- 15497433
TI  - A neural network model of adaptively timed reinforcement learning and hippocampal
      dynamics.
AB  - A neural model is described of how adaptively timed reinforcement learning
      occurs. The adaptive timing circuit is suggested to exist in the hippocampus, and
      to involve convergence of dentate granule cells on CA3 pyramidal cells, and N
      methyl-D-aspartate (NMDA) receptors. This circuit forms part of a model neural
      system for the coordinated control of recognition learning, reinforcement
      learning, and motor learning, whose properties clarify how an animal can learn to
      acquire a delayed reward. Behavioral and neural data are summarized in support of
      each processing stage of the system. The relevant anatomical sites are in
      thalamus, neocortex, hippocampus, hypothalamus, amygdala and cerebellum.
      Cerebellar influences on motor learning are distinguished from hippocampal
      influences on adaptive timing of reinforcement learning. The model simulates how
      damage to the hippocampal formation disrupts adaptive timing, eliminates
      attentional blocking and causes symptoms of medial temporal amnesia. Properties
      of learned expectations, attentional focussing, memory search and orienting
      reactions to novel events are used to analyze the blocking and amnesia data. The
      model also suggests how normal acquisition of subcortical emotional conditioning
      can occur after cortical ablation, even though extinction of emotional
      conditioning is retarded by cortical ablation. The model simulates how increasing
      the duration of an unconditioned stimulus increases the amplitude of emotional
      conditioning, but does not change adaptive timing; and how an increase in the
      intensity of a conditioned stimulus 'speeds up the clock', but an increase in the
      intensity of an unconditioned stimulus does not. Computer simulations of the
      model fit parametric conditioning data, including a Weber law property and an
      inverted U property. Both primary and secondary adaptively timed conditionings
      are simulated, as are data concerning conditioning using multiple interstimulus
      intervals (ISIs), gradually or abruptly changing ISIs, partial reinforcement and
      multiple stimuli that lead to time-averaging of responses. Neurobiologically
      testable predictions are made to facilitate further tests of the model.

PMID- 15497434
TI  - Task-determined strategies of visual process.
AB  - Lateral masking in the peripheral field of vision obscures letter recognition and
      is not accounted for by diminished acuity. In measuring lateral masking between
      letters in the peripheral visual field we accidentally discovered that ordinary
      readers and severe dyslexics differ markedly in tachistoscopic letter recognition
      tasks. Tests were devised to measure the differences accurately. Ordinary readers
      recognize letters best in and near the center of gaze. Recognition falls off
      rapidly with angular distance in the peripheral field. Severe dyslexics recognize
      letters farther in the periphery in the direction of reading (English-natives to
      the right, Hebrew-natives to the left). They have marked lateral masking in and
      near the center of the field when letters are presented in aggregates. With
      dyslexia as an example, we proposed that the distribution of lateral masking is a
      task-dependent strategy in visual perception. To test this notion we designed an
      active practise regimen for 4 severe adult dyslexics, who within a few months
      improved sharply in reading. At the same time their test results changed to those
      of ordinary readers. We conclude that there are switchable task-determined pre
      cognitive strategies of vision that can be learned and that the distribution of
      lateral masking may be part of what is learned.

PMID- 15497435
TI  - Distinctions and similarities among working memory processes: an event-related
      potential study.
AB  - Working memory has been conceptualized as consisting of a number of components,
      such as an articulatory loop for rehearsing verbal material, a visuo-spatial
      sketch pad for maintaining visual images and a central executive that controls
      which information is made available for conscious processing. We recorded event
      related brain potentials (ERPs) from normal human subjects while they maintained
      either visuo-spatial or phonological material in short-term memory for a 5-s
      interval. The results indicated that specialized brain systems for short-term
      storage of phonological and visuo-spatial information could be identified on the
      basis of marked differences between the topographies and morphologies of the ERP
      components elicited during these two types of short-term memory. The differences
      emerged during early encoding stages and continued through later retention
      stages.

PMID- 15497436
TI  - NBQX does not affect learning and memory tasks in mice: a comparison with D
      CPPene and ifenprodil.
AB  - The alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) antagonist 2,3
      dihydroxy-6-nitro-7-sulfamoyl-benzo(F)-quinoxaline (NBQX) did not impair working
      memory measured as alternation behavior in the Y-maze in mice. No depressant
      effect on alternation was detected even when NBQX impaired locomotion measured as
      the total number of arm entries. Similar profile of action in the Y-shaped maze
      was observed after administration of an anti-ischemic drug ifenprodil. In
      contrast, the N-methyl-D-aspartate (NMDA) antagonist (D-(E)-4-(3-phosphonoprop-2
      enyl)piperazine-2-carboxylate (D-CPPene) impaired spontaneous alternation. In the
      step-through passive avoidance task, mice were trained to avoid dark compartment
      entry. NBQX and ifenprodil did not impair learning in this task when administered
      before or immediately after training. In contrast, D-CPPene disturbed acquisition
      when administered before but not immediately after training or before retention
      test. These observations suggest that AMPA receptors are not critically involved
      in the formation of spatial working memory and acquisition (storage) in the
      passive avoidance, and have no effect on recall (retrieval) from long-term
      memory.

PMID- 15497437
TI  - Dr Nat Bumstead: pioneer researcher in mapping the chicken genome.

PMID- 15497438
TI  - Identification of polymorphisms in the human glucocorticoid receptor gene (NR3C1)
      in a multi-racial asthma case and control screening panel.
AB  - The glucocorticoid receptor (GR) gene (NR3C1) maps to 5q31, a region genetically
      linked to asthma. In this study, NR3C1 exons 1A, 1B, and exons 1C to 9 (alpha and
      beta) were sequenced in a screening panel of asthmatics and unaffected controls
      from US Caucasian, African American, US Hispanic, and Dutch Caucasian populations
      to identify polymorphisms for genetic association studies. Eight polymorphisms
      were identified in exon 1A, but none were located in putative transcription
      regulatory sites. Thirty-four polymorphisms were identified in exons 1B to 9
      (alpha and beta), 17 of which were novel. Eight coding polymorphisms were
      identified (4 non-synonymous). One novel mutation (Ala229Thr) was identified in a
      Hispanic individual. Linkage disequilibrium (LD) was strongest between
      polymorphisms spanning intron 2 to exon 9beta. This data shows the variability of
      NR3C1 polymorphism frequencies between racial groups and confirms that NR3C1 non
      synonymous coding polymorphisms are generally rare in mild/moderate asthmatics
      and unaffected controls.

PMID- 15497439
TI  - Novel member of the PAR domain bZIP gene family isolated from Pacific oyster,
      Crassostrea gigas.
AB  - A cDNA encoding the first mollusk member of the PAR subfamily of bZIP
      transcription factors has been characterized in the Pacific oyster, Crassostrea
      gigas. The sequence of the cDNA predicts a protein of 260 amino acids that has 41
      50% identity with the PAR domain, 72-79% identity with the basic DNA-binding
      domain and 34-56% identity with the leucine zipper domain of other members of the
      PAR subfamily. Polymerase chain reaction with reverse transcription indicates
      that this gene is expressed during developmental stages from an unfertilized egg
      to a juvenile. It was demonstrated by northern hybridization that the gene is
      also expressed on several adult tissues. The identification of a novel member of
      the PAR subfamily bZIP genes in mollusks may help to identify common functions
      that have been conserved through evolution and to elucidate evolutionary
      relationships within this subfamily of proteins.

PMID- 15497440
TI  - Molecular cloning and characterization of a CBF gene from Capsella bursa
      pastoris.
AB  - A new CBF gene was cloned from Capsella bursa-pastoris(shepherd's purse) by rapid
      amplification of cDNA ends (RACE). The full-length cDNA of C. bursa-pastoris CBF
      gene (designated as Cbcbf) was 1034 bp long and contained a 657 bp open reading
      frame (ORF) encoding a putative DRE/CRT (LTRE)-binding protein of 219 amino
      acids. The predicted CbCBF protein was found to have a potential nuclear
      localization signal (NLS) in its N-terminal region followed by an AP2 DNA-binding
      motif and an acidic C-terminal half that might act as an activator domain.
      Bioinformatic analysis revealed that Cbcbf strongly resembled other CBF genes
      from Arabidopsis thaliana (cbf1, cbf2, cbf3) and Brassica napus (Bncbf5, Bncbf 7,
      Bncbf16 and Bncbf17). Subsequent cold acclimation assay showed that Cbcbf was
      relevant to cold acclimation. Our study implies that Cbcbf might have similar
      functions possessed by other CBF genes such as inducing the expression of some
      cold-regulated genes and increasing plants' freezing tolerance.

PMID- 15497441
TI  - Cloning and characterization of a new polyketide synthase gene cluster in
      Streptomyces aureofaciens CCM 3239.
AB  - We cloned a new polyketide gene cluster, aur2, in Streptomyces aureofaciens
      CCM3239. Sequence analysis of the 9531-bp DNA fragment revealed 10 open reading
      frames, majority of which showed high similarity to the previously characterized
      type II polyketide synthase (PKS) genes. An unusual feature of the aur2 cluster
      is a disconnected organization of minimal PKS genes; ACP is located apart from
      the genes for ketosynthases KSalpha and KSbeta. The aur2 gene cluster was
      disrupted in S. aureofaciens CCM3239 by a homologous recombination, replacing the
      four genes (aur2A, E, F, G) including ketosynthase KSalpha, with antibiotic
      resistance marker gene. The disruption did not affect growth and differentiation,
      and disrupted strain produced spores with wild-type grey-pink pigmentation. The
      biochromatographic analysis of the culture extracts from S. aureofaciens wild
      type and aur2-disrupted strains did not reveal any difference in the pattern of
      antibacterial compounds.

PMID- 15497442
TI  - CDNA cloning and expression of ATP synthase subunit b from the fire-bellied frog
      Bombina orientalis (Anura: Discoglossidae).
AB  - We cloned the Bombina orientalis adenosine triphosphate (ATP) synthase subunit b
      gene from a B. orientalis oviduct cDNA library. The transcript was 997 bp long
      and encoded 250 amino acid residues. It showed high similarity to amphibian (84
      85%), mammalian (56-62%) and invertebrate (46-50%) sequences. In phylogenetic
      analyses, it clustered with other amphibian sequences. This gene was highly
      expressed in brain, intestine and oviduct but not in muscle and liver. In this
      paper, we report the basic characteristics of B. orientalis ATP synthase subunit
      b gene.

PMID- 15497443
TI  - Cloning and sequencing of an epoxide hydrolase gene from Rhodosporidium
      paludigenum.
AB  - Epoxide hydrolase (EH) activity was recently described in yeasts and highly
      selective hydrolysis of epoxides was observed during whole cell
      biotransformations. To expand the available molecular data regarding yeast EHs,
      the EH encoding gene from Rhodosporidium paludigenum (CBS 6565) was isolated,
      cloned and sequenced. The genomic EH sequence revealed a 1600 bp sequence
      interrupted by six introns. cDNA sequence analysis revealed an open reading frame
      of 1236 bp with a deduced polypeptide length of 411 amino acids. The deduced
      amino acid sequence revealed a relative high degree of sequence homology compared
      to the amino acid sequence of the EH from Rhodotorula glutinis.

PMID- 15497444
TI  - A Pisum sativum glyoxysomal malate dehydrogenase induced by cadmium exposure.
AB  - The glyoxysomal malate dehydrogenase (gMDH) catalyses the formation of
      oxaloacetate from malate during beta-oxidation of fatty acids in the glyoxysome.
      A partial Pisum sativum L. (cv. Greenfeast) cDNA was first isolated from a
      suppression subtractive hybridisation cDNA library obtained from heavy metal
      stressed plants. The full length cDNA was then isolated by rapid amplification of
      cDNA ends. The translated sequence showed strong similarity to Cucumis sativus
      and Citrullus lanatus gMDH including a typical glyoxysome-targeting presequence
      comprising the PTS2 motif and a cleavage site for a cystein-directed protease.
      Exposure of pea plants to Cd2+ induced expression of the gMDH gene in mature pea
      leaves indicating that the enzyme is under environmental control in addition to
      the normal developmental regulation pattern.

PMID- 15497445
TI  - Assignment of canine MSS1 microsatellite markers to chromosomes by linkage data.
AB  - Recent advances in mapping the canine genome have led to an increase in the
      number of linkage studies aimed at dissecting the genetic causes of many
      hereditary diseases that affect the domestic dog. The first step in developing
      molecular tools for a whole genome scan was the characterization of a set of
      microsatellite markers, termed minimal screening set 1 (MSS1), that provided an
      estimated coverage of 10 cM. A limiting factor in use of the MSS1 is not all of
      the 172 MSS1 markers have been localized to specific chromosomes. Seventy-five of
      the markers were positioned on a total of 15 chromosomes with the original
      publication of the MSS1. The localization based on linkage data of 14 additional
      MSS1 markers to chromosomes using CRIMAP v. 2.4 to build a linkage map of 113
      MSS1 markers that were polymorphic in a kindred of Dalmatians is reported here.

PMID- 15497446
TI  - Cloning and characterization of a splice variant of human Bardet-Biedl syndrome 4
      gene (BBS4).
AB  - Bardet-Biedl syndrome (BBS) is a heterogeneous multisystemic disorder
      characterized primarily by five cardinal features of retinal degeneration,
      obesity, polydactyly, hypogenitalism and mental retardation. To date, six
      distinct BBS loci that have been identified on different chromosomes. BBS4 gene
      is mapped to 15q22.2-23, which when mutated can cause BBS4. Its protein shows
      strong homology to O-linked N-acetylglucosamine (O-GlcNAc) transferase. Here we
      report a splice variant of BBS4, which is 2556 bp in length and has an open
      reading frame coding a predicted 527 amino-acids protein. RT-PCR shows that the
      cDNA is widely expressed while it has higher expression levels in pancreas, liver
      and prostate.

PMID- 15497447
TI  - Cloning and characterization of a novel human RNA binding protein gene PNO1.
AB  - Present work reported the cloning and characterization of a human novel RNA
      binding gene Partner of NOB1 (PNO1), with a length of 1637bp and a putative open
      reading frame of 759 bp, isolated from human kidney. It is composed of seven
      exons and is localized on chromosome 2p14. Western blot showed that the molecular
      weight of PNO1 is about 35kDa. RT-PCR results in 16 human tissues indicated that
      PNO1 is expressed mainly in liver, lung, spleen and kidney, slightly in thymus,
      testis, ovary, respectively, but not in heart, brain, skeletal muscle, placenta,
      pancreas, prostate, small intestine, colon and peripheral blood leukocytes. GFP
      fusion expression in mammalian cells exhibited its localization in the nucleus,
      especially in nucleoli. Subcellular localization of thirteen GFP fusion PNO1
      deletion proteins showed that the region of 92-230 aa is solely responsible for
      its nucleolar retention, and KH domain alone is not sufficient for nucleolar
      retention. The PNO1 family shows significant conservation in both eukaryotes and
      prokaryotes.

PMID- 15497448
TI  - Genetic and physical map of the pLAFR1 vector.
AB  - This paper presents the complete sequencing and annotation of the pLAFR1 vector.
      pLAFR is a tetracycline-resistant "cosmid" cloning vector, which is derived from
      the 20 kb plasmid pRK290, a RK2-derivative. Due to its broad host range, the
      pLAFR1 vector has been widely used in the genetic analysis of a broad number of
      gram-negative bacterial species. The availability of the complete pLAFR1 sequence
      will most definitely help in the construction and analysis of clone librares
      based on pRK290 or pLAFR vectors.

PMID- 15497449
TI  - Cloning of CYP9G2 from the diamondback moth, Plutella xylostella (Lepidoptera:
      Yponomeutidae).
AB  - Cytochrome P450s constitute a superfamily of hemoproteins, important in the
      metabolism of endogenous and xenobiotic compounds. The full-length cDNA of a
      novel cytochrome P450, CYP9G2, was isolated from a cDNA library. The cDNA is 2143
      bp in length and contains an open reading frame from 50 to 1615 bp, encoding a
      protein of 521 amino acid residues. The putative P450 protein contains a highly
      hydrophobic N terminus and a P450 protein signature motif, FG/S*G*R*C*G***A/G,
      known as the important ligand for heme binding, analysis of the NH2-terminal
      sequence indicated that CYP9G2 is a microsomal P450. Using polymerase chain
      reaction with primers specific to CYP9G2, the genomic structure of CYP9G2 was
      analyzed, and it was found that the gene contains seven introns and eight exons
      within the coding region, all the sequences of the exon-intron junctions are
      consistent with the AG-GT rule. Multiple alignment indicated that CYP9G2 is most
      similar to CYP9E2 from the Blattella germanica (42.7% identity), it is also
      similar to the insect P450s in family 9, including CYP9L1 from Anopheles gambiae
      (38.7%) and CYP9A1 from Heliothis virescens (39.5%).

PMID- 15497450
TI  - Toll-like receptors and their role in the development of autoimmune diseases.
AB  - Human Toll-like receptors (TLRs) are crucial for the recognition of invading
      pathogens and for the activation of both innate and adaptive immunity. Upon
      stimulation, TLRs recruit various protein kinases via several adaptor molecules,
      such as MyD88, leading to the activation of NFkB. The identification of TLR
      signaling pathways may unravel molecular mechanisms of self-tolerance and the
      means underlying the development of autoimmunity. The maturation of antigen
      presenting cells (APCs), in response to signals received by the innate immune
      system, may lead to the breakdown of tolerance. This process is mainly activated
      by TLRs that have been triggered by self-antigens. Auto-reactive B cells are
      present in the lymphoid tissues of healthy individuals, but since they are
      subject to self-tolerance mechanisms, they remain silent. However, when tolerance
      to self-antigens fails, a complex of self-reactive antibodies against self- or
      cross-reactive DNA co-engages the antigen receptor and the TLRs, leading to a
      continuous activation of these auto-reactive B cells and the development of
      autoimmune diseases. The contribution of TLRs to the production of auto
      antibodies by such dual-engagement suggests that this signaling pathway may
      become a target for new therapeutic approaches in autoimmune diseases.

PMID- 15497451
TI  - Polymorphisms of interleukin 4 receptor gene and interleukin 10 gene are not
      associated with Graves' disease in the UK.
AB  - Graves' disease (GD) is an autoimmune disorder of the thyroid gland and both
      environmental and genetic factors contribute to disease aetiology. Cytokines,
      such as interleukin 4 (IL-4) and interleukin 10 (IL-10), are involved in the
      immune response and may be implicated in the autoimmune disease process.
      Associations have been reported between single nucleotide polymorphisms (SNPs) of
      IL-10 and the Ile50Val polymorphism of the IL-4 receptor gene (IL-4R) gene and
      atopy and autoimmune diseases such as systemic lupus erythematosus and rheumatoid
      arthritis. The autoimmune diseases cluster within families and susceptibility
      genes may overlap between the different disorders. Therefore, we investigated 5
      SNPs (-592C/A, -657G/A, - 819C/T, -1349A/G, and -2013G/A) in the promoter region
      of the IL-10 and the Ile50Val polymorphism (A/G) in the IL-4R in a large UK
      population based case-control dataset with GD. No association was found between
      the polymorphisms studied and GD and no significant differences were found in
      genotype or allele frequencies between the patients and control subjects. We
      conclude these polymorphisms of IL-10 and IL-4R previously associated with other
      immune mediated diseases, do not confer susceptibility to GD in white Caucasians
      in the United Kingdom.

PMID- 15497452
TI  - Nonstandard antibodies as prognostic markers in autoimmune hepatitis.
AB  - BACKGROUND: Antibodies to actin, chromatin, soluble liver antigen/liver pancreas
      and liver cytosol type 1 have been ascribed prognostic value in autoimmune
      hepatitis. AIM: Evaluate the performance parameters of these nonstandard
      autoantibodies and determine the critical battery for clinical application.
      METHODS: All antibodies were tested concurrently by enzyme immunoassay in 106
      patients who had reached a treatment outcome. Tests were repeated in 149 serum
      samples obtained later to assess durability of the findings. RESULTS: Antibodies
      to chromatin and soluble liver antigen/liver pancreas were superior to the other
      markers in predicting relapse. Patients with antibodies to chromatin and/or
      soluble liver antigen/liver pancreas relapsed more frequently than patients
      without these markers (100 versus 79%, p < 0.0003). Maximum sensitivity and
      predictability for relapse required combined testing, and they were 54 and 60%,
      respectively. Antibody status remained stable in 60% of patients during 127 +/- 9
      months of follow-up, and antibodies to soluble liver antigen/liver pancreas were
      less labile than antibodies to chromatin (frequency of status change, 4 versus
      22%). None of the antibodies were associated with treatment failure, death from
      hepatic failure or requirement for liver transplantation. CONCLUSIONS: Antibodies
      to chromatin and soluble liver antigen/liver pancreas are associated with relapse
      after corticosteroid withdrawal, and they may be useful prognostic markers.
      Combined testing improves but does not eliminate deficiencies in sensitivity,
      predictability and durability.

PMID- 15497453
TI  - Antigenic complementarity resulting in idiotype-antiidiotype immune complexes:
      possible contributor to AIDS pathogenesis and autoimmunity.
AB  - One hundred and sixty seven combinations of viral + viral antibodies or viral +
      bacterial antibodies were tested for their ability to precipitate each other.
      Some antibodies produced against HIV epitopes recognize and precipitate some
      antibodies produced against cytomegalovirus (CMV), hepatitis B virus (HBV) core
      antigen, and Mycobacteria tuberculosis (MTb) and Staphylococcus epitopes but not
      those against HBV surface antigen, herpes simplex types 1 and 2 (HSV1 and HSV2)
      or Epstein-Barr virus (EBV), Streptococcus, or Escherichia coli. In addition, CMV
      antibodies precipitate those of HBV core and surface antigens as well as MTb, but
      not HSV, HSV2, EBV, Streptococcus or E. coli. HBV core (but not surface)
      antibodies precipitated Mycobacterium avium antibodies (MAv) but not MTb,
      Streptococcus, Staphylococcus or E. coli antibodies. Binding constants vary
      between kds of 10(-9) and 10(-7) M. Interactive antibodies act like idiotype
      antiidiotype pairs suggesting that the inducing antigens are molecularly
      complementary. The resulting antibody interactions may explain the formation of
      circulating immune complexes that are commonly found in AIDS and in other
      diseases characterized by multiple, concurrent infections. This observation
      suggests that AIDS pathogenesis may involve autoimmune mechanisms in which the
      immune system attacks itself to form antibody-antibody circulating immune
      complexes that contribute to the hypergammaglobulinemia characteristic of AIDS.
      Complementary cofactor infections in AIDS may therefore contribute to the
      immunosuppression of the syndrome and difficulties treating these corresponding
      infections.

PMID- 15497454
TI  - Proportion of antibodies to the A and B immunodominant regions of thyroid
      peroxidase in Graves and Hashimoto disease.
AB  - Autoantibodies to thyroid peroxidase (TPO) predominately recognise conformational
      epitopes, restricted to two immunodominant regions (IDR) -A and -B. We have
      estimated the proportion of IDR-A and -B autoantibodies in 75 Hashimoto and 68
      Graves patients sera. There were no statically significant differences between
      Hashimoto and Graves patients sera in the IDR-A and -B autoantibodies level,
      despite great differences between individual patients sera. In 75 Hashimoto
      patients sera, the mean value of IDR-A was 24.26%, IDR-B--52.26%, IDR (A + B)
      76.66%, and to non-A, non-B regions--23.5%. In 68 Graves disease patients, the
      mean value of IDR-A was 24.87, IDR-B--54.29, IDR (A + B)--79.07, non-A, non-B-
      20.92%, at a single autoantibodies concentration 5IU/ml. At high autoantibodies
      concentration (50 IU/ml) the proportion of autoantibodies to the IDR (A + B)
      diminished to 58% and to the non-A, non-B TPO regions increased to 42%. The
      autoimmune response to TPO regions outside the IDR (A + B) epitopes is stronger
      then previously assumed and this response is also conformation dependent.

PMID- 15497455
TI  - Anti-soluble liver antigen (SLA) antibodies in chronic HCV infection.
AB  - Hepatitis C infection is associated with autoimmune disorders, such as the
      production of autoantibodies. Anti-LKM1 and anti-LC1, immunomarkers of type 2
      autoimmune hepatitis, have been previously associated with a HCV infection. Anti
      Soluble-Liver-Antigen autoantibodies (SLA) are specifically associated with type
      1 and type 2 autoimmune hepatitis and more closely related to patients who
      relapse after steroid therapy. The recent molecular cloning of the soluble liver
      antigen provides the opportunity to develop more specific tests for the detection
      of antibodies against it. The aim of this work is to characterize anti-soluble
      liver autoantibodies in sera from patients chronically infected by HCV. A
      recombinant cDNA from activated Jurkat cells coding for the full length
      tRNP(Ser)Sec/SLA antigen was obtained. ELISA, Western Blot and
      immunoprecipitation tests were developed and used to search for linear and
      conformational epitopes recognized by anti-SLA antibodies in sera from patients
      chronically infected by HCV. Anti-soluble liver antigen antibodies were found in
      sera from 10.4% of HCV-infected patients. The prevalence was significantly
      increased to 27% when anti-LKM1 was also present. Most anti-SLA reactivity was
      directed against conformational epitopes on the antigen. The means titers by
      ELISA were lower than those obtained in type 2 AIH. The result of autoantibody
      isotyping showed a subclass restriction to IgG1 and also IgG4. This study shows
      the presence of anti-SLA antibodies in approximately 10% of HCV infected
      patients. The prevalence of SLA autoantibodies in HCV infected patients increases
      when LKM1 autoantibodies are also present. The relationship between the
      prevalence of this characteristic autoimmune hepatitis autoantibody and the
      implication of an autoimmune phenomenon in the liver injury of patients
      chronically infected by HCV needs further investigation.

PMID- 15497456
TI  - Association of G-174C polymorphism of the interleukin-6 gene promoter with
      Graves' ophthalmopathy.
AB  - Interleukin-6 (IL-6) may play an important role in the pathogenesis of Graves'
      ophthalmopathy (GO). The aim of this study was to analyze the association of IL-6
      gene promoter polymorphism, at position - 174 (G --> C, termed as G-174C), which
      may affect IL-6 production, with the development of GO. The G-174C polymorphism
      was determined in 279 Polish-Caucasian patients with Graves' disease (GD), of
      which 108 had clinically evident ophthalmopathy (NOSPECS class III or higher) and
      186 healthy Polish adults. In patients with GD, the frequencies of the C allele
      (45 vs 42%; P = 0.35) and C/C genotype (20 vs 15%; P = 0.13) were not
      significantly different compared to controls. Subdividing patients with GD for
      the presence of eye disease revealed that the C allele (44 vs 45%; P = 0.76) and
      C/C genotype (20 vs 20%; P = 0.92) were equally distributed in patients with or
      without ophthalmopathy. There was also no association between the G-174C
      polymorphism and the severity of eye changes. Finally, IL-6 genotypes were not
      associated with laboratory findings (thyroid volume, serum IL-6 and thyroid
      autoantibodies levels) in patients with GD at diagnosis. Our results suggest that
      G-174C polymorphism of the IL-6 gene does not contribute to the development and
      severity of GO.

PMID- 15497457
TI  - Hyperactivation and proliferation of lymphocytes from the spleens of flaky skin
      (fsn) mutant mice.
AB  - Mice homozygous for the flaky skin (fsn) single gene mutation have a severe
      hyperproliferative disease resulting in a complex phenotype, which includes
      widespread inflammation and autoimmunity. This study sought to characterize
      lymphocyte function of flaky skin mutant mice. Flaky skin lymphocytes show
      enhanced proliferation with in vitro mitogen stimulated spleen cells, as well as
      enriched splenic B- and T-cells. The production of IL-4 by fsn/fsn T-lymphocytes
      is increased dramatically compared with normal controls. Flaky skin lymphocytes
      exhibited increased responsiveness to IL-2, IL-4 and IL-7 in the absence of pre
      activation, enhanced IgE production in response to ovalbumin immunization, and
      constitutive STAT6 activation. These data indicate that the cytokines IL-2, IL-4
      and IL-7 likely contribute to the lymphocyte activation in fsn/fsn mutant mice.
      This lymphocyte hyperactivation may result in the development of systemic
      autoimmunity in fsn/fsn mutant mice.

PMID- 15497458
TI  - Evidence of association between FKBP1B and thyroid autoimmune disorders in a
      large Tunisian family.
AB  - FKBP1B belongs to immunophilins superfamily and functions as a cytosolic receptor
      protein of FK506. The role of FKBP1B in the immunosuppressive pathway of FK506 is
      well established. Previously, we reported a strong evidence of linkage between
      D2S171 microsatellite marker (located in vicinity of FKBP1B gene) and
      susceptibility to autoimmune thyroid diseases (AITDs). In this study, we report
      linkage disequilibrium between the dimorphism (C/T) in the 3' untranslated region
      (3' UTR) of FKBP1B gene and susceptibility to AITDs. DNAs were extracted from a
      large Tunisian family affected with Graves' disease (GD) and Hashimoto's
      thyroiditis (HT) and analysed by PCR-RFLP using DraIII restriction enzyme. Our
      results showed an excess of transmission of the allele C from heterozygous
      parents to affected offspring (transmission disequilibrium test (TDT) = 4.76; p =
      0.012). This suggests a linkage disequilibrium of 3' UTR (C/T) SNP with AITDs.
      Moreover, The FBAT analysis gives a significant association with the C allele
      under the recessive model (chi2 = 5.50; p = 0.018). These results support the
      involvement of FKBP1B gene in the genetic susceptibility to the AITDs development
      in the studied family.

PMID- 15497459
TI  - IgG antibodies to human cytomegalovirus late protein UL94 in patients with
      systemic sclerosis.
AB  - Human cytomegalovirus (HCMV) has been proposed as an amplifying agent for at
      least some of the spectrum of systemic sclerosis (SSc; scleroderma). In support
      of this hypothesis, antibodies to the HCMV late protein UL94 have been detected
      in the majority of SSc patients in a study involving Caucasian subjects from
      Italy. The aim of this investigation was to determine whether elevated levels of
      anti-UL94 antibodies are present in African American and Caucasian SSc patients
      from the U.S. We further wished to determine whether there was a significant
      difference in the levels of anti-UL94 antibodies between the diffuse and the
      limited forms of the disease. IgG antibodies to a UL94 peptide were measured in
      254 Caucasian and 90 African American subjects by an enzyme-linked immunosorbent
      assay (ELISA). In both Caucasian and African American subjects, the mean antibody
      level in the diffuse form of SSc was significantly higher than that in the
      respective control subjects (714 vs. 466 ng/ml, p = 0.005; 1226 vs. 512 ng/ml, p
      < 0.0001). Also, among Caucasian SSc patients, the mean antibody level in the
      diffuse form of SSc was significantly higher than that in the limited form of the
      disease (714 vs. 465 ng/ml, p = 0.02). These results show that increased levels
      of antibodies to the HCMV late protein UL94 are associated with SSc and they may
      be a marker for the severity of the disease.

PMID- 15497460
TI  - Lack of association of latent autoimmune diabetes in adults (LADA) with
      enterovirus infection.

PMID- 15497461
TI  - ARH missense polymorphisms and plasma cholesterol levels.
AB  - Mutations in a putative low-density lipoprotein (LDL) receptor adaptor protein
      called ARH have been recently described in patients with autosomal recessive
      hypercholesterolemia (ARH). ARH plays a tissue-specific role in determination of
      LDL receptor function. In the ARH gene three mismatched polymorphisms have been
      detected: Pro202Ser, Pro202His and Arg238Trp. These are of putative interest in
      plasma cholesterol level determination. To evaluate the effect of polymorphisms
      on plasma cholesterol levels, all polymorphisms were analyzed by PCR and
      restriction enzyme analysis by MnII, HpyCH4IV and SacII in 100 Caucasian males
      with high (>90%, 6.29 +/- 0.89 mmol/l), and 100 males with low (<10%, 3.60 +/-
      0.57 mmol/l), total plasma cholesterol levels. No significant differences were
      observed in frequencies of ARH genotypes or alleles between these two extreme
      groups. These results suggest that ARH polymorphisms are unlikely to be important
      genetic determinants of plasma cholesterol levels.

PMID- 15497462
TI  - Genetic and immunological analyses of patients with increased serum
      butyrylcholinesterase activity and its C5 variant form.
AB  - Recent evidence has denied genetic abnormality as a mechanism of the C5 variant
      of butyrylcholinesterase (BChE) and proposed the binding of an unknown protein
      with the C4 component. The present study aimed to evaluate whether the coding
      sequences and non-translated sequences of the BChE gene at exons 1 to 4, 3q are
      structurally different in subjects having elevated BChE with and without the C5
      variant phenotype. We also attempted to identify the unknown protein associated
      with the C5 variant and measured the BChE-specific activity in the C5 variant
      with an enzyme-linked immunosorbent assay (ELISA) using anti-BChE monoclonal
      antibody. We investigated five subjects, four of whom had elevated plasma BChE
      (three C5-positive [C5(+)] and one C5-negative [C5(-)]) and one control with a
      normal plasma BChE level. Direct DNA sequencing of the BChE gene revealed no
      relevant genetic mutations and no abnormal migrations in the genes of all five
      subjects. Precipitation of the patients' sera with anti-human immunoglobulin A
      (IgA), -IgG, -IgM, anti-human albumin antibodies had no effect on the BChE
      activity. The measured BChE activity in C5(+) was 30 to 54% higher than the
      activity calculated from BChE protein content. The present results suggest that
      the C5(+) phenotype is not associated with any genetic abnormality in the CHE1
      locus, and BChE-specific activity is enhanced in the C5(+) variant. However, the
      exact nature of the unknown protein related to the C5(+) phenotype remains
      unclear.

PMID- 15497463
TI  - Polymorphisms in the P-selectin (CD62P) and P-selectin glycoprotein ligand-1
      (PSGL-1) genes and coronary heart disease.
AB  - P-selectin and its ligand, PSGL-1, are cell adhesion molecules that facilitate
      interaction of platelets, leukocytes and endothelial cells. Polymorphisms of
      these genes have been reported to be associated with coronary heart disease
      (CHD). In the present study, we characterized the entire coding regions of P
      selectin and PSGL-1 genes in CHD patients and healthy controls. The 17 exons of
      the P-selectin gene and exon 2 of the PSGL-1 gene were screened for single
      nucleotide polymorphisms (SNPs) by exon re-sequencing in 88 CHD patients and 96
      controls. For rapid genotyping of the SNPs we developed PCR techniques with
      sequence-specific primers (PCR-SSP). By using PCR-SSPs we genotyped 261 CHD
      patients and 214 controls for 5 SNPs in P-selectin and 2 SNPs in PSGL-1. In
      addition to the already described SNPs in P-selectin (S290N, N562D, V599L and
      T715P), we identified a novel SNP in exon 5 (V168M). The P-selectin 715P allele
      was more frequent among CHD patients with hypercholesterolemia compared to
      patients with normal cholesterol levels. A SNP (M621) in the PSGL-1 gene was
      found close to the P-selectin binding site and the 621 allele revealed a higher
      prevalence in the control group indicating a protective effect of the mutation.
      The molecular characterization of P-selectin and PSGL-1 in a case-control study
      including CHD patients and healthy controls revealed evidence for association of
      the genes with development of the disease. However, the functional role of the
      gene variants should be elucidated by further experimental data.

PMID- 15497464
TI  - Odd-numbered long-chain fatty acids in erythrocyte phospholipids as long-term
      follow-up parameter in propionic acidemia.
AB  - Odd-numbered long-chain fatty acids (OLCFAs) increase in total erythrocyte lipids
      or plasma in patients with propionic acidemia and have been proposed as a useful
      parameter of metabolic control. However, up to now no parameter for long-term
      metabolic control has been available for this disorder. In contrast to previous
      investigations, we investigated OLCFAs with particular reference to differences
      for two phospholipid fractions of erythrocyte lipids. The
      phosphatidylethanolamine (PE) fraction of erythrocyte lipids has a slow turnover
      rate and might reflect the metabolic propionyl-CoA burden over a period of some
      weeks. Distinct increases in OLCFA of up to 200% in the phosphatidylcholine
      fraction were observed after episodes of metabolic decompensation and maximum
      OLCFA levels were found 3 weeks after the onset of a crisis. As a sign of poor
      metabolic control, OLCFA levels in PE steadily increased after recurrent episodes
      of decompensation, but not in clinically stable patients. However, in one patient
      with clinically good metabolic control, OLCFAs continually increased after the
      second year of life for an as yet unknown reason. In conclusion, data from this
      study indicate the usefulness of OLCFA analysis in the PE fraction of erythrocyte
      lipids, in particular with regard to the need for such a parameter for evidence
      based improvement of management strategies in propionic acidemia.

PMID- 15497465
TI  - Simplified method for the diameter sizing of serum low-density lipoprotein using
      polyacrylamide gradient gel electrophoresis.
AB  - The appearance of small, dense, low-density lipoprotein in serum has been
      demonstrated to be associated with increased risk of coronary artery disease. The
      molecular diameter of low-density lipoprotein is usually measured on the basis of
      mobility differences on polyacrylamide gel electrophoresis. However, since
      mobility assessed by this method is seriously affected by the increased levels of
      serum free fatty acids associated with hypertriglyceridemia, we used
      polyacrylamide gradient gel electrophoresis to eliminate the interference by
      fatty acids and devised a simple, precise method of polyacrylamide gradient gel
      electrophoresis to measure the diameter of small, dense, low-density lipoproteins
      in serum. We used apoferritin and thyroglobulin, which have a molecular diameter
      of 12.2 nm and 17.0 nm, respectively, and standard low-density lipoprotein
      particles having a diameter of 25.7 and 27.0 nm as calibrators, estimated by
      measurement of negative staining of electron microscopy. We also included
      apoferritin as an internal standard for polyacrylamide gradient gel
      electrophoresis. The only stain used was Coomassie brilliant blue, and it was
      used for lipoprotein staining. When we used low-density lipoprotein of 25.73 nm
      in diameter as a quality control specimen, the coefficient of variation of the
      size measurements obtained by our method was less than 1.2%. The new method
      markedly improved the laboratory procedure for measuring the diameter of low
      density lipoproteins.

PMID- 15497466
TI  - In vitro inhibition of fibrinolysis by apolipoprotein(a) and lipoprotein(a) is
      size- and concentration-dependent.
AB  - Lipoprotein(a) (Lp(a)) is considered an independent risk factor for
      atherosclerotic heart and circulatory diseases. The unique, polymorphic character
      of Lp(a) is based on its apolipoprotein(a) (apo(a)), which has remarkable
      structural analogies with plasminogen, an important protein for fibrinolysis. The
      formation of plasmin from plasminogen is a fundamental step in the dissolution of
      fibrin. Repression of this step may lead to a deceleration of fibrinolysis. It
      has been suggested that Lp(a) has antifibrinolytic properties through apo(a) and
      that the apo(a)-size polymorphism has a distinct influence on the prothrombotic
      properties of Lp(a). However, the results on this topic are controversial.
      Therefore we used a standardized in vitro fibrinolysis model to provide further
      information on the influence of Lp(a) on plasmin formation. Monitoring the time
      course of plasmin formation, we investigated the inhibition of plasmin formation
      through dependence on Lp(a), respectively, free apo(a) concentration.
      Furthermore, we investigated the influence of three Lp(a)/apo(a) phenotypes
      ((22K)Lp(a), 22 kringle-4 repeats; (30K)Lp(a), 30 kringle-4 repeats; (35K)Lp(a),
      35 kringle-4 repeats). Adding varying amounts of Lp(a) to our model, we observed
      that the rate of plasmin formation was inversely related to the Lp(a)
      concentration. At 0.1 micromol/l (30K)Lp(a), for example, the plasmin formation
      was reduced by 12.7% and decreased further by 40.7% at 0.25 micromol/l Lp(a). A
      similar but more distinct effect was observed when free (30K)apo(a) was added to
      the model (25.3% at 0.1 micromol/l vs. 59.3% at 0.25 micromol/l). Comparing the
      antifibrinolytic influence of different apo(a) phenotypes we found that the
      reduction of plasmin generation advanced with the size of apo(a). At 0.1
      micromol/l Lp(a) the reduction of the plasmin formation increased in the order
      (22K)Lp(a), (30K)Lp(a) and (35K)Lp(a) from 3.7% to 10.7% and 22.3%, respectively.
      Experiments with different phenotypes of free apo(a) showed similar results (0.5
      micromol/l: (22K)apo(a), 56.4% vs. (30K)Lp(a), 80.4%). Summarizing these results,
      our study indicates a distinct interrelation of Lp(a)/apo(a) phenotype and
      concentration with the formation of plasmin. From the antifibrinolytic
      Lp(a)/apo(a) effect in vitro it may be hypothesized that Lp(a)/apo(a) also has an
      inhibitory influence on in vivo fibrinolysis.

PMID- 15497467
TI  - Comparison of cardiac troponin T and I in healthy men and in aortic valve
      replacement.
AB  - Troponins are of outstanding importance for the diagnosis of myocardial
      infarction. Cardiac troponin T (cTnT) and the various cardiac troponin I (cTnI)
      assays differ with respect to method comparison, diagnostic sensitivity and
      diagnostic specificity. To understand the differences in the diagnostic behavior
      of troponin assays, AccuTnI and Elecsys Troponin STAT were used in a group of
      healthy men and in the follow-up of patients with aortic valve replacement (AVR).
      Within the healthy subjects AccuTnI was able to differentiate two subgroups from
      each other, whereas the cTnT concentrations of all subjects were below the
      detection limit. In AVR patients, cTnT and cTnI correlated sufficiently, if the
      postoperative periods were taken into consideration. There was a rapid increase
      in cTnI within 24 h. In contrast, a broad peak was evident for cTnT between 48
      and 120 h. The results emphasize more the differences in the release of cTnI and
      cTnT from the cytoplasm and the thin filaments of the cardiomyocytes than the
      modifications of the troponins circulating in the blood.

PMID- 15497468
TI  - Evaluation of a shorter methionine loading test.
AB  - We validated whether a shorter methionine loading test is as accurate as the
      original 6-h test in identifying hyperhomocysteinemic patients and investigated
      determinants of fasting and post-load homocysteine concentration. Plasma
      homocysteine was determined in EDTA-blood from women with a history of pre
      eclampsia (n=106) after 12 h fasting and 3 and 6 h after an oral methionine load
      (0.1 g/kg body weight). The 677C>T polymorphism in the methylenetetrahydrofolate
      reductase (MTHFR) gene, vitamin B6, vitamin B12, folate and creatinine were
      measured as determinants of homocysteine concentration. Good correlation and
      agreement between 3-h and 6-h plasma concentration of post-load (r=0.93,
      Kendall's tau-b=0.85) and delta (post-load minus the fasting value; r=0.90,
      Kendall's tau-b=0.79) homocysteine was observed and gross misclassification did
      not occur after division of 3-h and 6-h homocysteine scores into quartiles.
      Multiple linear regression revealed MTHFR 677 TT (p=0.01), folate (p=0.04) and
      vitamin B12 (p=0.06) as determinants of fasting homocysteine concentration; only
      MTHFR 677TT was related to 3-h (p=0.04) and 6-h (p=0.004) post-load homocysteine
      concentration. The MTHFR 677TT genotype resulted in >30% higher fasting and 3-h
      and 6-h post-load homocysteine concentrations compared to the wild-type CC
      genotype. This study shows that the 3-h methionine loading test is as good as the
      6-h methionine loading test in identifying hyperhomocysteinemic patients.
      Furthermore, remethylation parameters (MTHFR 677C>T) strongly affect both fasting
      and post-load homocysteine.

PMID- 15497469
TI  - Homocysteine, vitamin B12 and folate in vascular dementia and in Alzheimer
      disease.
AB  - The association between elevated plasma levels of homocysteine (Hcy) and
      nutritional status has been shown in Alzheimer disease (AD) patients and also in
      vascular dementia (VaD). Moreover, a previous study provided evidence that the
      relation between a high Hcy level and low vitamin B12 and folate levels in AD
      patients is due to biochemical damage, rather than a nutritional deficit. The
      purpose of this study was to investigate the relationship between plasma Hcy
      levels and vitamins involved in its metabolism in AD and VaD. Twenty-two VaD
      patients, 22 AD patients and 24 healthy subjects were studied for Hcy, vitamin
      B12, vitamin B6 and folate. All patients and control subjects were comparable for
      age, educational level, nutritional and socioeconomic status. None of them showed
      macrocytic anemia or impaired renal function. Hcy was significantly increased in
      VaD patients (26.0 +/- 6.58 micromol/l) as compared to controls (10.7 +/- 3.0
      micromol/l) and AD patients (22.3 +/- 4.51 micromol/l; p<0.001); however, AD
      patients also showed increased levels of Hcy. Folates were significantly reduced
      in both VaD (10.8 +/- 2.81 nmol/l) and AD (10.0 +/- 2.72 nmol/l; p<0.001)
      patients, while vitamin B12 showed significantly reduced levels only in AD
      patients (392.1 +/- 65.32 pmol/l; p=0.02). Vitamin B6 was not significantly
      different in the three groups. Increased levels of Hcy associated with low
      vitamin B12 plasma levels were found only in AD patients. This observation led us
      to consider that vitamin B12 metabolism does not represent the direct consequence
      of the nutritional status and suggests that neuronal damage results in a
      functional vitamin B12 deficiency, as emphasized by recent reports. New
      therapeutic strategies are necessary, considering that available pharmaceutical
      forms of vitamin B12 are not utilized by neurons in oxidative stress conditions.

PMID- 15497470
TI  - The clinical impact of screening for gestational diabetes.
AB  - Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance during
      pregnancy. In Denmark the health service offers selective screening for GDM,
      i.e., admission to an oral glucose tolerance test (OGTT) after pre-screening with
      interview for clinical risk factors for GDM, two capillary fasting blood glucose
      (cFBG) measurements and a urine test for glucosuria. The aim of the present study
      was to investigate the power of the pre-screening to identify GDM and the
      screening to predict adverse clinical outcome. A retrospective investigation of
      pregnant women undergoing screening during 1998 at Vejle County Hospital, Denmark
      was undertaken. The two most frequent pre-screening criteria for OGTT were body
      mass index (BMI) > or = 27 kg/m2 and age > or = 35 years. The highest odds ratio
      (OR) of 9.07 (95% CI: 2.60 to 63.70) for GDM had glucosuria and the lowest (zero)
      had cFBG. The frequency of complicated delivery was similar in GDM (58%) compared
      to non-GDM (56%). The best predictor of complicated delivery was a BMI with OR =
      1.50 (95% CI: 0.87 to 2.60) for BMI > or = 27 kg/m2 vs. < 27 kg/m2. The best
      predictor of adverse neonatal outcome was a capillary blood glucose 120 min after
      glucose load (cBG(120 min)) > or = 9.0 mmol/l (OR = 3.18, 95% CI: 1.14 to 8.89).
      The intermediary endpoint GDM was not superior for predicting adverse maternal
      and neonatal outcome. The cumulative probability distribution of cBG(120 min)
      after a 75 g glucose load was not homogeneously distributed in groups stratified
      according to maternal and foetal outcome. A changed slope was seen after cBG(120
      min) 9.0 mmol/l. Screening cFBG of 4.1 mmol/l was unable to predict GDM and
      adverse outcome. Glucosuria was too rare to be effective as a screening tool. Pre
      screening did not identify GDM. The best predictor of complicated delivery was a
      high BMI. The best predictor of foetal adverse outcome was cBG120 miin > or = 9.0
      mmol/l after a 75 g glucose load. Identical fraction complications were present
      in GDM and non-GDM. A refinement of the screening procedure is highly needed, and
      this has been initiated in Denmark.

PMID- 15497471
TI  - Comparison between creatinine and pregnanediol adjustments in the retrospective
      analysis of urinary hormone profiles during the human menstrual cycle.
AB  - Measurement of reproductive hormones in urine is a practical way of obtaining
      large amounts of information; however, there is still controversy on how to
      overcome problems derived from volume fluctuations between samples. Creatinine
      adjustment is a widely accepted solution, however, it introduces an extra cost,
      and large studies involving multiple sequential determinations would benefit from
      more economical solutions. We determined the value of creatinine adjustment, and
      compared it with a mathematical method that uses the smoothed profile of
      pregnanediol (PdG) as a reference to adjust other hormonal markers. To do this,
      we investigated the effects on three major urinary reproductive hormonal markers
      (luteinizing hormone (LH), estrone 3-glucuronide (E1G) and PdG) in 17 complete
      menstrual cycles. Detection of the day of LH peak did not differ between raw and
      adjusted data. Creatinine adjustment reduced variation in pre-ovulatory E1G
      levels between individuals, though the effect was negligible within individuals.
      No significant differences were found regarding post-ovulatory PdG rise. Although
      creatinine adjustment significantly reduces variability, producing smoother
      profiles, an equivalent degree of smoothness is obtained using the PdG
      adjustment. We conclude that under the current technology, for the retrospective
      study of urinary hormonal profiles in the human menstrual cycle, PdG adjustment
      is a valid alternative to creatinine.

PMID- 15497472
TI  - The measurement of complexed prostate-specific antigen has a better performance
      than total prostate-specific antigen.
AB  - The aim of this study was to compare the diagnostic utility of complexed prostate
      specific antigen (cPSA) with total PSA (tPSA) in screening for prostate cancer.
      Serum concentrations of tPSA and cPSA were measured in 4479 adult men during the
      prostate cancer screening program in the Saarland region (Germany). The
      percentage of men with c/tPSA ratio above the cut-off value of 0.75 increased
      with increasing tPSA intervals: tPSA 0-0.9 microg/l, 4.4%; 1.0-1.9 microg/l,
      24.3%; 2.0-2.9 microg/l, 43.9%; 3.0-3.9 microg/l, 50.4%; and 4.0-20 microg/l,
      60.2%. The commonly accepted tPSA cut-off value of 3.9 microg/l matched to the
      93rd percentile of the overall population (corresponding cPSA value, 2.9
      microg/l). A total of 202 men out of 313 with increased cPSA had increased c/tPSA
      ratio (cut-off > or = 0.75) vs. 186 out of 312 men with increased tPSA. Thus, an
      additional 16 men at high risk for prostate cancer were selected only if cPSA was
      utilised as a first line parameter. Our data show that, compared to tPSA, cPSA
      measurement will always detect more high-risk patients, independent of the cut
      off levels utilised for cPSA, tPSA and c/tPSA ratio. cPSA is more effective than
      tPSA in selecting subjects with an elevated c/tPSA ratio who are at high risk of
      prostate cancer. Thus, cPSA might be seen as the superior first-line parameter in
      screening for prostate cancer. Using lower cut-off values for tPSA or cPSA than
      the commonly accepted values seems reasonable for screening purposes.

PMID- 15497474
TI  - Diagnostic efficiency of different amphetamine screening tests--the search for an
      optimal cutoff.
AB  - Increased use of designer drugs (amphetamines and amphetamine-like substances)
      raises the need for fast screening tests in urine in clinical settings, workplace
      and drug rehabilitation. Immunological assays currently used are subject to
      unwanted crossreactivities, partly depending on the cutoff concentrations used.
      The values recommended in Europe and the USA are 500 and 1000 ng/ml,
      respectively. In Switzerland, the recommended concentration of 300 ng/ml results
      in a high rate of false-positive urine samples and expensive, time-consuming
      confirmation testing. Using the Abbott Axsym analyzer, we found numerous false
      positives from patients in rehabilitation centers due to concomitant medication.
      Therefore, the diagnostic sensitivity and specificity of the Abbott test at
      different cutoff concentrations and the sensitivity of the Roche Cobas Integra,
      Beckman Synchron and Biosite Triage point-of-care test were examined. HPLC BioRad
      Remedi was chosen as the method of higher hierarchical order. The specificity of
      the Axsym analyzer (300 ng/ml) was 86%. At 500 ng/ml or 1000 ng/ml the
      specificity was increased to 99 or 100%, respectively, while the sensitivity only
      decreased from 97 to 91 or 81%, respectively. In summary, the cutoff
      concentration for amphetamine screening tests should not be below 500 ng/ml to
      avoid a high rate of false-positive results.

PMID- 15497473
TI  - Effect of prolonged physical exercise on urinary proANP1-30 and proANP31-67.
AB  - Dynamic exercise strongly affects atrial natriuretic peptides (ANP), in
      particular the mature bioactive alphaANP and the proANP fragments, namely proANP1
      98, proANP1-30 and proANP31-67. The proANPs influence kidney functions and their
      plasma levels increase after physical exercise. We measured urinary proANP1-30
      and proANP31-67 levels before and at the end of physical exercise in 28 well
      trained male cyclists. For the first time, the proANP1-30 and proANP31-67 urinary
      levels in athletes before and at the end of a prolonged agonistic bicycle race
      were measured. Urinary creatinine and total proteins were also measured. The
      urinary proANP31-67, creatinine and total protein levels were significantly
      higher at the end of exercise than before. In contrast, proANP1-30/protein and
      proANP31-67/protein ratios decreased after exercise. Even proANP1-30/creatinine
      and proANP31-67/creatinine ratios were lower after exercise. A significant
      correlation between proANP1-30 and proANP31-67 urinary levels at the end of
      exercise was found. The proANP31-67/creatinine ratio before and after exercise
      also showed a significant correlation. The variation of urinary proANP fragments
      confirmed their possible role in physical exercise. In particular, it could be
      interpreted as a response of the body or kidney to renal impairment occurring
      during exercise.

PMID- 15497475
TI  - Evaluation of a new lithium colorimetric assay performed on the dade behring
      dimension X-pand system.
AB  - Lithium is the standard first line of treatment for bipolar disorder. Because of
      its potential toxicity, levels of the drug have to be constantly monitored. To
      this end, an accurate and rapid assay is thus required. Moreover, lithium
      measurement allows differential diagnosis in patients with hallucinations,
      dementia and amnesia. The lithium concentration in blood is usually evaluated by
      flame photometry, atomic absorption spectroscopy or ion selective electrode. The
      aim of this study was to evaluate the analytical performance of a new
      colorimetric assay for lithium. Within-day precision of a pool with a target
      value of 1.25 mmol/l was 2.18% (CV) and day-to-day precision was assessed using
      serum aliquots containing two concentrations of lithium, and CVs were 5.47 and
      1.6% at 0.6 and 1.15 mmol/l, respectively. The lower detection limit (LLD) was
      <0.08 mmol/l. The assay seemed to be linear up to 5 mmol/l. Results of a
      comparison method using Deming regression were: y=1.161x-0.0075 (r=0.9879) for
      regression with the Flame Photometer and y=0.9729 x+0.0133 (r=0.9787) for
      regression with atomic absorption spectroscopy. Moreover, in this study we did
      not find any interference with drugs or other analytes tested. In conclusion,
      this assay may be a method of choice for measuring lithium blood concentrations,
      especially in emergency situations.

PMID- 15497476
TI  - Reference interval of serum insulin concentrations.

PMID- 15497477
TI  - Significant decimals and rounding.

PMID- 15497478
TI  - Questionable results--who directs the EQAS organisers?

PMID- 15497479
TI  - [Standardising hunger: Francois Magendie's feeding experiments on a gelatin fare
      1831-1841].
AB  - Although Francois Magendie's studies on the functional differentiation of the
      spinal nerves, on the maintenance of blood pressure, and on the circulation of
      the cerebrospinal fluid have been sufficiently considered in medical
      historiography, his physiological research on nutrition, carried out between 1831
      1841, has hardly attracted attention. With several series of animal experiments,
      Magendie tried to answer the question whether a gelatine-based fare would be
      suitable for feeding the indigent people of Paris. Taking these experimental
      series as a specific historical example, an approach from sociological systems
      theory is proposed in order to analyse the relations between Magendie's hunger
      laboratory, the French Academie des Sciences, food industrialists, and health and
      military administrators. The historiographical relevance of this approach as well
      as its methodological limitations are discussed in this article.

PMID- 15497480
TI  - [Improvement of hygiene and the combat of epidemics as Russian state concerns
      during World War I: Prince Alexander von Oldenburg and the POWs of the Central
      Powers in Russia].
AB  - When Russia joined the war against the Central Powers in 1914, she immediately
      faced problems of public health care among the masses of people who were forced
      to move across far distances in the country: soldiers, refugees, and prisoners of
      war. Because of poor organisation and the unexpectedly long duration of the war,
      the POWs fared worst of all war victims in Russia. Subjected to an overstrained
      military organisation in the rear, the fate of this broadly neglected group
      illustrates how and with what success Russia strove to meet its deficiencies in
      administrative structure during wartime. The "Evacuation and Sanitation Section"
      was put under the command of a member of the Imperial family, Prince Alexander of
      Oldenburg, a high ranking official of German origin. This amateur scientist and
      initiator of medical institutions was an energetic and courageous personality who
      became vital for the fate of millions of POWs in epidemic-stricken Russia. The
      role of this "silent" ally of the German and Austro-Hungarian governments has
      hitherto been unknown. Newly found sources in Russian archives now shed an
      interesting light on a weak spot of Russia's administration and a generally
      neglected chapter of the history of medicine, the handling of epidemics and of
      deficits in hygiene.

PMID- 15497481
TI  - ["Euthanasia"--victims and test subjects. The fate of diseased, disabled children
      in Berlin during World War II].
AB  - This article shows, through a study of the Berlin-Brandenburg region, that
      children and juveniles who were subjected to the killings of diseased and
      disabled, or mentally retarded, persons during the Third Reich did not only fall
      victim to the operations of the "Reichsausschuss" ("Reich Commission for
      Registration of Severe Disorders in Childhood"). Many were also included in the
      gas chamber killings of the "T4"-action and in various decentralized killing
      actions. Furthermore, the co-operation of various medical disciplines in the
      misuse of children for scientific research is demonstrated by looking into the
      research on a tuberculosis vaccine. It can be shown that the purpose of the
      killings was not the painless ending of individual suffering, but that they
      constituted a means of freeing the public from so-called "ballast existences",
      whose lives were only prolonged if they could be of scientific use.

PMID- 15497482
TI  - [Developments and trends in 19th- and 20th-century German nursing
      historiography].
AB  - This paper analyses important trends in 19th- and 20th-century German nursing
      historiography. Frequently, the diverse contributions, which were predominantly
      written by physicians and nurses, were strongly shaped by the occupational
      background of the author and purposes of professional politics. In recent years,
      valuable scholarly contributions on nursing organisations have appeared. Anglo
      American nursing history research should serve as a model for Germany. The paper
      calls for the extension of a recently founded nursing history research network.

PMID- 15497483
TI  - Memory for everyday information in students with learning disabilities.
AB  - This study compared students with and without learning disabilities (LD) on their
      recall of academic information and information encountered in the students'
      everyday lives. The academic recall measures included a sentence listening span
      test, a rhyming words working memory test, and a visual matrix working memory
      task. Students' cued recall of all the tasks was also measured. The everyday
      working memory tasks included a dance episode event recall test; a library
      procedure recall test; and recall tests of commonly found objects, such as a
      coin, a telephone, and a McDonald's sign. Compared to students without LD,
      students with LD performed poorly on both the academic recall tasks and the
      everyday recall tasks. These results support the notion that some students with
      LD may have working memory problems that affect their performance on tasks other
      than reading. The results of the cued recall showed that the availability of cues
      significantly decreased the ability group differences on many of the academic and
      everyday tasks. This result replicates prior research findings that students with
      LD do not use retrieval strategies effectively and that some students with LD may
      have a production deficiency that affects their retrieval of previously encoded
      information.

PMID- 15497484
TI  - Cognitive, academic, and attitudinal predictors of the grade point averages of
      college students with learning disabilities.
AB  - This study examined cognitive, academic, and attitudinal predictors of college
      grade point average (GPA) among college students with learning disabilities (LD).
      The study population included 84 youth who attended a large private university in
      the midwestern United States. Measures of cognitive and academic functioning,
      along with a self-report measure of study habits and study attitudes, were used
      to predict college GPA. The results indicated that Full Scale IQ and one factor
      on the self-reported study habits scale accounted for a significant amount of
      variance in students' college GPA. These findings suggest that variables other
      than traditional cognitive and academic skills are important for determining the
      performance of youth with LD during college. The implications of these findings
      for future research efforts and practice are discussed.

PMID- 15497485
TI  - Assessment of three-and-a-half-year-old children's emerging phonological
      awareness in a computer animation context.
AB  - Four computer-animated tasks were created to analyze the underlying structure of
      emerging phonological awareness at 3.5 years of age and to explore the factors
      that influence children's (N = 91) performance on the tasks. Our findings
      indicated that already at this young age, children are able to master tasks
      demanding identification, blending, and continuation of phonological units when
      the tasks are presented in a motivating assessment context. In line with earlier
      research, children showed higher mastery in dealing with words and syllables than
      in dealing with phonemes. Targets in the initial position of a word were easier
      for children to identify than those in the final position. Our analysis provided
      support for two major dimensions of emerging phonological awareness based on the
      cognitive operations of the tasks: identification and blending of phonological
      units.

PMID- 15497486
TI  - The role of IQ in a component model of reading.
AB  - The purpose of this study was to test the role of visual processing speed and IQ
      in a model of reading. This study investigated whether the processes involved in
      reading differ between a group of children with and a group without reading
      disability. These two groups of children completed tests of reading
      comprehension, listening comprehension, decoding, processing speed, and
      intelligence. The results indicated that processing speed explains a significant
      amount of variance in reading comprehension over that accounted for by the simple
      view of reading. Also, IQ accounts for a significant amount of variance in
      reading over that accounted for by the simple view of reading and processing
      speed. Path analyses indicated that the effect of IQ on reading is partially
      mediated by decoding in the children with reading disability. The results point
      to the importance of the role of IQ in predicting reading comprehension.

PMID- 15497487
TI  - A cross-sectional study of mathematics achievement, estimation skills, and
      academic self-perception in students of varying ability.
AB  - This study investigated students' mathematics achievement, estimation ability,
      use of estimation strategies, and academic self-perception. Students with
      learning disabilities (LD), average achievers, and intellectually gifted students
      (N = 135) in fourth, sixth, and eighth grade participated in the study. They were
      assessed to determine their mathematics achievement, ability to estimate discrete
      quantities, knowledge and use of estimation strategies, and perception of
      academic competence. The results indicated that the students with LD performed
      significantly lower than their peers on the math achievement measures, as
      expected, but viewed themselves to be as academically competent as the average
      achievers did. Students with LD and average achievers scored significantly lower
      than gifted students on all estimation measures, but they differed significantly
      from one another only on the estimation strategy use measure. Interestingly, even
      gifted students did not seem to have a well-developed understanding of estimation
      and, like the other students, did poorly on the first estimation measure. The
      accuracy of their estimates seemed to improve, however, when students were asked
      open-ended questions about the strategies they used to arrive at their estimates.
      Although students with LD did not differ from average achievers in their
      estimation accuracy, they used significantly fewer effective estimation
      strategies. Implications for instruction are discussed.

PMID- 15497488
TI  - The differential effects of teaching addition through strategy instruction versus
      drill and practice to students with and without learning disabilities.
AB  - Forty-two second-grade general education students and 42 students with learning
      disabilities (LD) were taught basic, one-digit addition facts (e.g., 5 + 3 = _).
      Students received instruction via (a) a minimum addend strategy, (b) drill and
      practice, or (c) control. The effectiveness of the two methods was measured
      through students' accuracy and latency scores on a posttest and a transfer task
      (e.g., 5 + 3 + 7 =_). Students with LD improved significantly only in the
      strategy condition, as compared to drill-and-practice and control conditions,
      whereas general education students improved significantly both in the strategy
      and the drill-and-practice conditions as compared to the control condition.
      However, in the transfer task, students from all groups became significantly more
      accurate only in the strategy condition, while all students were significantly
      faster than their control group peers regardless of teaching method. The
      implications for teachers' differential choices of methods of instruction for
      students with different learning characteristics are discussed.

PMID- 15497489
TI  - Agreement among four models used for diagnosing learning disabilities.
AB  - We compared the level of agreement among four models used to diagnose learning
      disabilities (LD), including the simple discrepancy, intraindividual,
      intellectual ability-achievement, and underachievement models. The sample
      included 170 clinic-referred university students. The simple discrepancy model
      diagnosed significantly more students with LD than the other three models. The
      highest degree of agreement occurred between the intraindividual and intellectual
      ability-achievement models (70%); the lowest level of agreement occurred between
      the simple discrepancy and underachievement models (48%). Finally, only two of
      the six comparisons among the four models demonstrated significant correlations.
      We conclude that even when discrepancy models diagnose similar numbers of
      students with LD, the same students are not diagnosed across different models.

PMID- 15497490
TI  - Neurobehavioral factors associated with referral for learning problems in a
      community sample: evidence for an adaptational model for learning disorders.
AB  - We evaluated community general education (CGE; n = 178), community special
      education (CSE; n = 30) and hospital-referred (HR, n = 145) children (ages 7-6 to
      11-11) prospectively over a 2-year period. During this period, 17 CGE children
      were referred for evaluation (community referred; CR). Prior to referral, CR
      children performed more poorly than community-nonreferred (CNR) children on
      cognitive ability, academic achievement, attention problems, and information
      processing. CR group performance was equivalent to that of CSE and HR groups, but
      HR children showed poorer academic achievement. Referred children performed more
      poorly on all measures than nonreferred, whether they met formal diagnostic
      criteria for a learning disorder or not. Learning disorders may be better
      conceptualized as a context-dependent problem of functional adaptation than as a
      disability analogous to physical disabilities, raising questions about the
      validity of using psychometric test scores as the criterion for identification.

PMID- 15497491
TI  - Comparative vascular effects of hormone replacement therapy and raloxifene in
      women at increased cardiovascular risk.
AB  - Hormone replacement therapy (HRT) improves endothelial function in postmenopausal
      women while the effects of raloxifene, a selective estrogen receptor modulator,
      are still under debate. The aim of this study was to evaluate endothelium
      dependent flow-mediated vasodilatation in the brachial artery and plasma levels
      of nitrite, nitrate and endothelin-1 in 20 postmenopausal women with increased
      cardiovascular risk treated with either HRT or raloxifene for 4 weeks in a
      randomized double-blind single cross-over study. Patients had an endothelium
      dependent flow-mediated dilatation of 4% prior to initiation of the study.
      Treatment with HRT resulted in a 67% increase in dilatation compared with
      baseline (from a 7.4% increase to a 12.4% increase, p < 0.01). Raloxifene
      treatment resulted in no change in vasodilatation from baseline. Endothelium
      dependent dilatation was significantly improved by HRT compared with raloxifene
      treatment (12.4+/-0.6% vs. 6.1+/-2.0%; p < 0.01). Compared with baseline values,
      nitrate plus nitrite levels increased significantly (p < 0.05) with HRT but not
      with raloxifene. Similarly, endothelin-1 decreased from baseline with both
      treatments, but only the HRT-induced decrease was statistically significant (p <
      0.05). In conclusion, HRT improved endothelial function and reduced plasma levels
      of endothelin-1 in postmenopausal women at risk of coronary artery disease. These
      beneficial effects were not shared by raloxifene.

PMID- 15497492
TI  - Effect of previous hormone replacement therapy on endometrial polyps during
      menopause.
AB  - The aim of this study was to evaluate the effect of hormone replacement therapy
      (HRT) on the expression of Ki-67, bcl-2 and c-erb.B2 in endometrial polyps during
      menopause. Sixteen patients using HRT and 24 untreated controls with endometrial
      polyps were enrolled in this study. Polypectomy was carried out by hysteroscopy.
      The presence of c-erb.B2, bcl-2 and Ki-67 expression was determined by
      immunohistochemistry. HRT was found to decrease Ki-67 and bcl-2 expression in
      endometrial polyps without affecting the c-erb.B2 staining reaction. HRT may
      cause endometrial polyp involution by decreasing proliferation and stimulating
      apoptosis.

PMID- 15497493
TI  - Long-term effects of two different continuous combined regimens of hormone
      replacement therapy on well-being.
AB  - Our aim was to compare the effect on well-being of two different continuous
      combined hormone replacement therapies (HRT) in women starting treatment
      ('starters') and women switching from mainly sequential HRT ('switchers'). The
      design was a randomized, double-blind, 1-year, prospective study, including 249
      postmenopausal women treated with 0.625 mg conjugated estrogen (CE)/5 mg
      medroxyprogesterone acetate (MPA) or 2 mg estradiol/1 mg norethisterone acetate
      (NETA) continuously. The main outcome measure was well-being, reported daily on a
      validated symptom scale during treatment cycles 1, 2, 6 and 13. Both treatment
      groups, starters and switchers, improved significantly in episodes of sweating
      during the first 6 months (p < 0.05). Women treated with estradiol/NETA
      experienced more breast tenderness compared to women using CE/MPA during the
      whole study period (p < 0.001), whereas there were no differences in negative
      mood symptoms between treatment groups. Starters experienced improved well-being
      during the whole study, whereas switchers experienced a transient improvement
      during the first 2 months. Overall, negative mood symptoms were more frequently
      reported by women with a history of premenstrual syndrome (PMS) (p < 0.05).
      Progestogen side-effects were more pronounced with estradiol/NETA than with
      CE/MPA combinations. Individual factors, such as previous PMS and previous HRT
      use, should be taken into consideration when prescribing HRT.

PMID- 15497494
TI  - Plasma concentrations of endogenous hormones during one regular treatment cycle
      with a low-dose oral contraceptive and during two cycles with deliberate omission
      of two tablets.
AB  - In this open, prospective, phase-I study we closely monitored levels of
      endogenous progesterone, 17beta-estradiol, luteinizing hormone (LH) and follicle
      stimulating hormone in six healthy women. We determined plasma concentrations
      every 1-3 days during one untreated baseline cycle and during the first treatment
      cycle with regular pill intake of an oral contraceptive containing 30 microg
      ethinylestradiol plus 75 microg gestodene. During the following two treatment
      cycles, two tablets were deliberately omitted (in cycle 2 on days 6/7 and in
      cycle 3 on days 11/12). All but possibly one volunteer ovulated in the untreated
      pre-cycle, as concluded from LH peaks followed by marked increases of
      progesterone. During the regular first treatment cycle and even after deliberate
      omission of two tables in treatment cycles 2 and 3, the progesterone and
      estradiol levels remained low, so that we concluded that no ovulation took place.
      However, two volunteers showed some sort of LH peak in the first regular
      treatment cycle and all women showed LH increases of > 40 microg/ml in at least
      one omission cycle. In ten out of 12 cycles, omissions of pill intake were
      followed by an episode of intermenstrual bleeding. In conclusion, we have shown
      that, after omission of two consecutive oral contraceptive tables, the endogenous
      hormone parameters did not provide evidence for ovulation. Although this provides
      confirmation of the robustness of this oral contraceptive towards non-compliance,
      the widely published practical recommendations should be followed.

PMID- 15497495
TI  - Leptin and its association with polycystic ovary syndrome: a twin study.
AB  - Polycystic ovary syndrome (PCOS) is a common endocrinopathy with symptoms such as
      obesity, insulin resistance and hyperandrogenemia. PCOS might be the result of a
      genetic disorder. Genetic discrepancy in the production of leptin, a product of
      the obesity gene, may lead to various endocrinopathies such as PCOS. The
      objective of this study was first, to ascertain the incidence of PCOS, using the
      gold standard; second, to ascertain the genetic property of leptin; and third, to
      evaluate the association between leptin concentration and PCOS. A total of 154
      Tehran-resident female-female twins were studied. They included 48 pairs of
      monozygotic (MZ) and 29 pairs of dyzygotic (DZ) twins, aged 15-45 years.
      Clinical, ultrasound and biochemical findings were used to diagnose PCOS. The
      incidence of PCOS using biochemical and clinical features was 16.2%. The
      correlation coefficient between serum leptin levels of MZ twins was higher than
      that of the DZ twins. The serum level of leptin was similar between subjects with
      or without PCOS, irrespective of their zygosity. It was concluded that the
      incidence of PCOS is high among twins, and that leptin is likely to be
      genetically determined, although the effect of environmental factors cannot be
      denied. This study did not find any association between the diagnosis of PCOS and
      leptin level. However, the link between the two may lie with other entities such
      as eating disorders and/or obesity.

PMID- 15497496
TI  - Prediction of ovarian reserve based on day-3 serum follicle stimulating hormone
      concentrations during the pituitary suppression cycle using a gonadotropin
      releasing hormone agonist in patients undergoing in vitro fertilization-embryo
      transfer.
AB  - Satisfactory results following in vitro fertilization-embryo transfer (IVF-ET)
      treatments depend on retrieving an appropriate number of mature oocytes without
      causing the development of ovarian hyperstimulation syndrome (OHSS). The present
      study was carried out to investigate whether the ovarian reserve is predictable
      based on the day-3 serum concentration of follicle stimulating hormone (FSH)
      during the pituitary suppression cycle using a gonadotropin releasing hormone
      (GnRH) agonist (defined as day-3 FSH) in patients undergoing IVF-ET treatment.
      Day-3 FSH before the administration of gonadotropin was assessed in 72 IVF-ET
      cycles from 59 infertile women. The mean+/-SD of day-3 FSH, the total amount of
      FSH plus human menopausal gonadotropin (hMG) administered, and the total number
      of oocytes retrieved was 5.5+/-2.6 mIU/ml, 2834.2+/-1236.5 IU and 7.7+/-5.8,
      respectively. There were significant correlations between day-3 FSH and the total
      amount of FSH-hMG administered (p < 0.001), and day-3 FSH and total number of
      oocytes retrieved (p < 0.001). There was a significant difference of day-3 FSH
      between patients who subsequently conceived (4.4+/-1.3 mIU/ml) and those who did
      not conceive (6.1+/-2.9 mIU/ml) (p = 0.001). There was also a significant
      difference of day-3 FSH between patients who developed moderate or severe OHSS
      (4.5+/-1.2 mIU/ml) and those who did not (5.9+/-2.8 mIU/ml) (p = 0.003). Receiver
      operator characteristic curve analysis showed that the significant cut-off point
      for day-3 FSH for predicting ovarian reserve was 5.25 mIU/ml. These findings
      indicate that day 3-FSH is usefulfor predicting ovarian reserve during the
      pituitary suppression cycle using a GnRH agonist in patients undergoing IVF-ET.

PMID- 15497497
TI  - Serum levels of leptin, insulin-like growth factor-I and insulin-like growth
      factor binding protein-3 in women with pre-eclampsia, and their relationship to
      insulin resistance.
AB  - The present study was carried out to compare serum levels of leptin, insulin-like
      growth factor-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3),
      homeostasis model assessment--(pancreatic beta-cell function) (HOMA-(%B)) and
      homeostasis model assessment--(tissue insulin sensitivity) (HOMA-(%S)) in women
      with mild and severe pre-eclampsia and normotensive pregnant women; and to
      evaluate the possible relationships between these parameters in the pathogenesis
      of pre-eclampsia. Seventy-three women were divided into three groups: group A
      consisted of 20 normotensive pregnant women (NPW); group B consisted of 25 women
      with mild pre-eclampsia (MPE); and group C consisted of 28 women with severe pre
      eclampsia (SPE). Serum level of leptin was measured by enzyme immunoassay using a
      commercial kit. Serum levels of IGF-I and IGFBP-3 were measured with a two-site
      immunoradiometric assay. Serum level of insulin was measured by the
      electrochemiluminescence immunoassay method. HOMA used indices of pancreatic beta
      cell function and tissue insulin sensitivity. Differences between groups were
      compared by one-way analyses of variance and the post hoc Tukey-HSD test for
      multiple comparisons; however, when a variable was not normally distributed, the
      Mann-Whitney U test was used. Associations between variables were tested using
      Pearson's coefficient of correlation. Birth weight was significantly lower (p <
      0.001) in the MPE and SPE groups than in the NPW group. Serum levels of leptin
      and insulin in women with SPE and MPE were significantly higher (p < 0.001) than
      in NPW. Serum levels of IGF-I and IGFBP-3 were significantly lower in women with
      SPE and MPE compared with NPW (p < 0.001). The mean HOMA-(%B) level in women with
      SPE and MPE was significantly higher than in NPW (p < 0.001), whereas the mean
      HOMA-(%S) level in women with SPE and MPE was significantly lower than in NPW (p
      < 0.001). In the SPE group, systolic blood pressure correlated significantly with
      serum levels of IGF-I and leptin (r = 0.375, p < 0.05 and r = 0.495, p < 0.01,
      respectively). A negative correlation between mean HOMA-(%S) level and serum
      IGFBP-3 level was noted (r = -0.357, p < 0.05). There was a positive correlation
      between serum level of IGF-I and mean HOMA-(%B) level in mildly pre-eclamptic
      women (r = 0.541, p < 0.01). We conclude that pre-eclampsia is associated with
      insulin resistance; and that existing hyperinsulinemia and insulin resistance in
      women with pre-eclampsia seem not to correlate with leptin and birth weight, but
      may correlate positively with IGF-1 and IGFBP-3. Therefore we think that
      hyperleptinemia, low IGF-I or IGFBP-3, and insulin resistance may contribute to
      the pathogenesis of pre-eclampsia.

PMID- 15497498
TI  - Tetratricopeptide repeat cochaperones in steroid receptor complexes.
AB  - The molecular chaperone machinery contains multiple protein components that have
      1 or more structural domains composed of tetratricopeptide repeat (TPR) motifs.
      Many other proteins of separate or unknown function also have TPR domains, so
      this motif is not exclusive to molecular chaperones. A general function of TPR
      domains is to bind other polypeptides, but this otherwise prosaic function has
      been exploited in an assortment of ways that link chaperones and other protein
      systems into cooperative networks. Among the best-characterized TPR proteins are
      several cochaperones that participate in assembly and regulation of steroid
      receptor complexes. Steroid receptors, members of the nuclear receptor subfamily,
      are hormone-dependent transcription factors that regulate many vertebrate
      pathways of homeostasis, growth, differentiation, reproduction, and pathology
      and, as such, have been of great interest to biologists and clinicians. Moreover,
      the steroid receptors are among the first recognized native clients for
      chaperones and have been widely studied models for complex chaperone
      interactions. To provide a coherent, representative minireview of TPR protein
      function, the scope of this article has been narrowed down primarily to functions
      of steroid receptor-associated TPR cochaperones.

PMID- 15497499
TI  - On mechanisms that control heat shock transcription factor activity in metazoan
      cells.
AB  - Heat shock factor Hsf in nonvertebrate animals and homologous heat shock factor
      Hsf1 in vertebrate animals are key transcriptional regulators of the stress
      protein response. Hsf/Hsf1 is constitutively present in cells but is, typically,
      only active during periods during which cells are experiencing a physical or
      chemical proteotoxic stress. It has become increasingly clear that regulation of
      Hsf/Hsf1 activity occurs at multiple levels: the oligomeric status of Hsf/Hsf1,
      its DNA-binding ability, posttranslational modification, transcriptional
      competence, nuclear/ subnuclear localization, as well as its interactions with
      regulatory cofactors or other transcription factors all appear to be carefully
      controlled. This review emphasizes work reported over the past several years
      suggesting that regulation at several of these levels is mediated by repressive
      interactions of Hsp90-containing multichaperone complexes and/or individual
      chaperones and Hsf/Hsf1.

PMID- 15497500
TI  - Expression of cytoprotective proteins, heat shock protein 70 and
      metallothioneins, in tissues of Ostrea edulis exposed to heat and heavy metals.
AB  - Heat shock proteins (Hsps) are constitutively expressed in cells and involved in
      protein folding, assembly, degradation, intracellular localization, etc, acting
      as molecular chaperones. However, their overexpression represents a ubiquitous
      molecular mechanism to cope with stress. Hsps are classified into families, and
      among them the Hsp70 family appears to be the most evolutionary preserved and
      distributed in animals. In this study, the expression of Hsp70 and the related
      messenger ribonucleic acid (mRNA) has been studied in Ostrea edulis after
      exposure to heat and heavy metals; moreover, levels of metallothioneins (MTs),
      another class of stress-induced proteins, have contemporaneously been assessed in
      the same animals. Thermal stress caused the expression of a 69-kDa inducible
      isoform in gills of O edulis but not in the digestive gland. Northern dot blot
      analysis confirmed that the transcription of Hsp69-mRNA occurs within 3 hours of
      stress recovery after oyster exposure at 32 and 35 degrees C. Hsp69-mRNA
      transcripts were not present in the gills of animals exposed to 38 degrees C
      after 3 hours of poststress recovery, but they were detected after 24 hours. The
      expression of the 69-kDa protein in O edulis exposed to 38 degrees C was rather
      low or totally absent, suggesting that the biochemical machinery at the base of
      the heat shock response is compromised. Together with the expected increase in MT
      content, the oysters exposed to Cd showed a significant enhancement of Hsp70,
      although there was no clear appearance of Hsp69. Interestingly, the levels of MT
      were significantly increased in the tissues of individuals exposed to thermal
      stress. Unlike oysters, heat did not provoke the expression of inducible Hsp
      isoforms in Mytilus galloprovincialis, Tapes philippinarum, and Scapharca
      inaequivalvis, although it significantly enhanced the expression of constitutive
      proteins of the 70-kDa family. The expression of newly synthesized Hsp70 isoforms
      does not seem therefore a common feature in bivalves exposed to thermal stress.

PMID- 15497501
TI  - Hsp72 is present in plasma from Holstein-Friesian dairy cattle, and the
      concentration level is repeatable across days and age classes.
AB  - Although heat shock proteins (Hsps) are primarily considered as being
      intracellular, this study identified the presence of Hsp72 in plasma from female
      Holstein-Friesian dairy cattle. Plasma samples were collected from the same
      animals at different ages and on different days after calving and accordingly
      divided into 5 age classes. The age classes were calves less than 235 days of
      age, young heifers between 235 and 305 days of age, older heifers between 305 and
      560 days of age, cows early in lactation, and cows later in lactation. For a
      subsample of animals within each age class, replicate plasma samples were
      collected from 1 to 7 days apart to test whether the Hsp72 concentration levels
      are repeatable on this shorter timescale. Hsp72 was observed in plasma samples
      from animals of all 5 age classes. For animals with blood samples taken a few
      days apart, the repeatability (within age class) of the Hsp72 concentration was
      0.52 +/- 0.06. Age and days from calving significantly affected the Hsp72
      concentration level. The highest Hsp72 level was observed in older heifers (305
      560 days of age). The repeatability of Hsp72 concentrations across age classes
      within animal was 0.22 +/- 0.06. High environmental sensitivity and negative
      genetic associations between production and health traits in this high-producing
      breed have been documented earlier. Hsp72 is believed to be strictly stress
      inducible, and the finding of Hsp72 in plasma indicates that even apparently
      healthy individuals may experience extrinsic or intrinsic stress (or both).

PMID- 15497502
TI  - Stimulation of Fas agonistic antibody-mediated apoptosis by heparin-like agents
      suppresses Hsp27 but not Bcl-2 protective activity.
AB  - We report that in Jurkat T cells or freshly isolated T lymphocytes, physiological
      concentrations of high-molecular weight sulfated polysaccharides such as heparin,
      heparan sulfate, and dextran sulfate significantly increased the percentage of
      cell death induced by Fas IgM agonistic antibody. The phenomenon was caspase
      dependent and P53 independent and correlated with an increased accessibility of
      cell surface Fas receptors. We also observed that the Fas IgM agonistic antibody
      dependent formation of sodium dodecyl sulfate (SDS)-resistant large structures
      containing Fas receptor was decreased in the presence of heparin-like agents. In
      contrast, the different agents had no effect when cell death was triggered by
      FasL, the natural ligand of Fas that does not generate SDS-resistant forms of
      Fas. Interestingly, the synergistic effect of heparin-like agents toward Fas IgM
      agonistic antibody-mediated cell death abolished Hsp27 antiapoptotic activity but
      did not alter much the protection generated by Bcl-2 expression.

PMID- 15497503
TI  - Interaction of the Hsp90 cochaperone cyclophilin 40 with Hsc70.
AB  - The high-affinity ligand-binding form of unactivated steroid receptors exists as
      a multicomponent complex that includes heat shock protein (Hsp)90; one of the
      immunophilins cyclophilin 40 (CyP40), FKBP51, or FKBP52; and an additional p23
      protein component. Assembly of this heterocomplex is mediated by Hsp70 in
      association with accessory chaperones Hsp40, Hip, and Hop. A conserved structural
      element incorporating a tetratricopeptide repeat (TPR) domain mediates the
      interaction of the immunophilins with Hsp90 by accommodating the C-terminal EEVD
      peptide of the chaperone through a network of electrostatic and hydrophobic
      interactions. TPR cochaperones recognize the EEVD structural motif common to both
      Hsp90 and Hsp70 through a highly conserved clamp domain. In the present study, we
      investigated in vitro the molecular interactions between CyP40 and FKBP52 and
      other stress-related components involved in steroid receptor assembly, namely
      Hsp70 and Hop. Using a binding protein-retention assay with CyP40 fused to
      glutathione S-transferase immobilized on glutathione-agarose, we have identified
      the constitutively expressed form of Hsp70, heat shock cognate (Hsc)70, as an
      additional target for CyP40. Deletion mapping studies showed the binding
      determinants to be similar to those for CyP40-Hsp90 interaction. Furthermore, a
      mutational analysis of CyP40 clamp domain residues confirmed the importance of
      this motif in CyP40-Hsc70 interaction. Additional residues thought to mediate
      binding specificity through hydrophobic interactions were also important for
      Hsc70 recognition. CyP40 was shown to have a preference for Hsp90 over Hsc70.
      Surprisingly, FKBP52 was unable to compete with CyP40 for Hsc70 binding,
      suggesting that FKBP52 discriminates between the TPR cochaperone-binding sites in
      Hsp90 and Hsp70. Hop, which contains multiple units of the TPR motif, was shown
      to be a direct competitor with CyP40 for Hsc70 binding. Similar to Hop, CyP40 was
      shown not to influence the adenosine triphosphatase activity of Hsc70. Our
      results suggest that CyP40 may have a modulating role in Hsc70 as well as Hsp90
      cellular function.

PMID- 15497504
TI  - Rapid, transient, and dose-dependent expression of hsp70 messenger RNA in the rat
      brain after morphine treatment.
AB  - Induction of Hsp70 in the brain has been reported after intake of drugs of abuse
      like amphetamine and lysergic acid diethylamide. In this investigation, gene
      expression of Hsp70 and other heat shock genes in the rat brain was studied in
      response to morphine. Twenty milligrams per kilogram morphine intraperitoneally
      resulted in a marked induction of Hsp70 messenger RNA (mRNA) expression in the
      frontal cortex with a maximum increase of 13.2-fold after 2 hours. A moderate
      increase of Hsp27 mRNA expression (6.7-fold) could be observed after 4 hours,
      whereas mRNA expression of Hsp90 and of the constitutive Hsc70 did not exceed a
      mean factor of 1.8-fold during the 24 hours interval. The increase in Hsp70 mRNA
      was dose dependent, showing a significant elevation after doses ranging from 10
      to 50 mg/kg morphine. In situ hybridization revealed enhanced Hsp70 mRNA
      expression mainly in cortical areas, in the hippocampus, in the paraventricular
      and supraoptic nuclei of the hypothalamus, in the locus coeruleus, as well in the
      pineal body. The double in situ hybridization technique revealed increased Hsp70
      mRNA expression mainly in VGLUT1-positive neurons and to a lesser extent in olig1
      positive oligodendroglia. Immunohistochemistry revealed a marked increase of
      Hsp70 protein in neuronal cells and blood vessels after 12 hours. In contrast to
      animal experiments, morphine did not increase Hsp70 mRNA expression in vitro in
      micro-opioid receptor (MOR1)-expressing human embryonic kidney 293 cells,
      suggesting no direct MOR1-mediated cellular effect. To exclude a body temperature
      related morphine effect on Hsp70 mRNA expression, the temperature was recorded.
      Five to 20 mg/kg resulted in hyperthermia (maximum 40.6 degrees), whereas a high
      dose (50 mg/kg) that produced the highest mRNA induction, showed a clear
      hypothermia (minimum 37.2 degrees C). These findings argue against the
      possibility that Hsp70 induction by morphine is caused by its effect on body
      temperature. It may be speculated that increased expression of Hsp70 after
      morphine application protects brain structures against potentially hazardous
      effects of opiates.

PMID- 15497505
TI  - Upregulation and intrarenal redistribution of heat shock proteins 90alpha and
      90beta by low-sodium diet in the rat.
AB  - Two genes encoding isoforms heat shock protein (Hsp) 90alpha and Hsp90beta
      constitute the Hsp90 subfamily. In addition to their role in regulating
      mineralocorticoid and glucocorticoid receptors, these proteins have been
      associated with nitric oxide production. However, little is known regarding Hsp90
      isoform expression and regulation in kidney. In this study we characterized the
      expression and localization of Hsp90 isoforms and evaluated the influence of low
      sodium intake on their expression and distribution in kidney by using reverse
      transcription-polymerase chain reaction, Western blot, and immunohistochemistry
      techniques. We found that Hsp90alpha and Hsp90beta were expressed abundantly in
      both the renal cortex and the medulla; however, Hsp90 isoform expression was
      higher in the medulla than in the cortex. Immunohistochemistry of Hsp90alpha and
      Hsp90beta showed intense staining in the apical membrane of proximal and distal
      tubules. In the outer cortex these proteins were localized intracytosolically,
      whereas in the inner renal medulla they were restricted mainly to the basolateral
      membrane. Expression of Hsp9alpha and Hsp90beta was upregulated in the renal
      cortex during sodium restriction. In addition, both proteins exhibited
      redistribution from the cytoplasm to the basolateral side in thick ascending limb
      cells when rats were fed with a low-salt diet. Our results showed that Hsp90alpha
      and Hsp90beta were expressed abundantly in renal tissue. Expression and
      localization patterns under normal and salt-restricted intake were different
      between the cortex and the medulla, suggesting that these proteins may be
      involved in different processes along the nephron. Hsp90alpha and Hsp90beta
      upregulation induced by a low-sodium diet together with redistribution in thick
      ascending limb cells suggests that Hsp90 plays a role in the modulation of sodium
      reabsorption under these circumstances.

PMID- 15497506
TI  - Frequency-specific association of antibodies against heat shock proteins 60 and
      70 with noise-induced hearing loss in Chinese workers.
AB  - Noise exposure may result in production of auto-antibodies against heat shock
      proteins (Hsps), which might be of significance in the pathogenesis or prognosis
      (or both) of auto-immune ear diseases. However, it is not known whether these
      antibodies are associated with noise-induced hearing loss (NIHL) in workers
      exposed to noise in occupational settings. Using immunoblotting with human
      recombinant Hsps, audiological assessment, and multivariate logistic regression
      models, we investigated the presence of antibodies against Hsp60 and Hsp70 and
      hearing levels, and analyzed their associations with NIHL in 399 workers exposed
      to noise between 75 and 115 dB. Our findings showed that the prevalence of
      positive anti-Hsp70 was significantly higher in the workers with slight and
      moderate high-frequency hearing loss than in normal workers (P < 0.05).
      Furthermore, the prevalence of positive anti-Hsp60 in workers with moderate low
      frequency NIHL was significantly higher than in the normal (P < 0.01). The levels
      of anti-Hsp70 and anti-Hsp60 seemed correlated, and the level of anti-Hsp70
      better predicted the level of anti-Hsp60. An elevated plasma level of anti-Hsp70
      was associated with a nonsignificantly increased risk of high-frequency NIHL
      (adjusted OR = 1.45; 95% CI = 0.89-2.36) and an elevated plasma level of anti
      Hsp60 was associated with a nonsignificantly increased risk of the low-frequency
      NIHL (adjusted OR = 2.25; 95% CI = 0.85-5.96). These results suggest that the
      production of anti-Hsp60 and anti-Hsp70 may play a role in the pathogenesis of
      NIHL, and that anti-Hsps may be a risk factor. The precise mechanisms for the
      elevation of antibodies against Hsps caused by noise exposure and their possible
      role in the development of NIHL warrant further investigations.

PMID- 15497507
TI  - Identification of Xenopus heat shock transcription factor-2: conserved role of
      sumoylation in regulating deoxyribonucleic acid-binding activity of heat shock
      transcription factor-2 proteins.
AB  - Heat shock transcription factor (Hsf)-1 and Hsf2 are members of the heat shock
      factor (HSF) protein family involved in heat shock protein (hsp) gene regulation,
      a regulation that is critical for the ability of cells to survive exposure to
      stress conditions. Although the role of Hsf1 in binding and activating
      transcription of hsp gene promoters in response to cell stress is well
      established, how Hsf2 enhances stress-induced hsp expression is not understood.
      To gain an insight into the critical conserved features of the regulation and
      function of Hsf2, we have identified and characterized the Hsf2 protein from
      Xenopus laevis. We found that, similar to its human counterpart, Xenopus Hsf2 is
      sumoylated at lysine 82 and that, as it does in human Hsf2, the modification
      event of the small ubiquitin-related modifier 1 functions to increase the
      deoxyribonucleic acid-binding activity of this transcription factor in Xenopus.
      These results indicate that sumoylation is an evolutionarily conserved
      modification of Hsf2 proteins, supporting the position of this modification as a
      critical regulator of Hsf2 function.

PMID- 15497508
TI  - Is hyperhomocysteinemia related to widowers' stroke syndrome?

PMID- 15497509
TI  - Practical aspect of monitoring hypertension based on self-measured blood pressure
      at home.
AB  - Devices for home blood pressure (BP) measurement are produced worldwide at a rate
      of more than 10 million a year and 30 million such devices have already been
      distributed in Japan. The clinical significance of home BP measurement is
      obvious; patients can recognize the effects of antihypertensive treatment. Home
      BP measurements encourage medication compliance, follow-up clinic visits, and
      active participation in the medical treatment, thus resulting in improved
      management of hypertension. Home BP measurements more accurately reflect damage
      to target organs and the prognosis of cardiovascular diseases. The purpose of
      home BP measurements is to obtain information on the patient's inherent BP
      pattern using longterm, repetitive measurement under controlled conditions. Since
      home BP is measured under controlled condition, values are reproducible, and
      thus, useful in the diagnosis and treatment of hypertension. Blood pressures
      measured under standardized condition are indispensable when comparing data among
      individuals, among groups and among institutes. Working Group of Japanese Society
      of Hypertension (JSH) established JSH Guidelines for Self-Monitoring of Blood
      Pressure at Home in 2003. Standardization of the measurement procedure may
      elevate the position of home BP measurements for the purpose of diagnosing and
      treating hypertension. As a result, home BP measurements may improve the accuracy
      of screening for hypertension and assessment of BP control during treatment and
      encourage drug compliance. Home BP measurements, under such controlled
      conditions, should have a beneficial effect on the economics of diagnosing and
      treating hypertension.

PMID- 15497510
TI  - Lispro is superior to regular insulin in transient intensive insulin therapy in
      type 2 diabetes.
AB  - OBJECTIVE: The optimal approach to relatively recent onset type 2 diabetes
      patients is still unknown. We speculated that the use of short-acting insulin
      analogs might be of particular benefit in this context. PATIENTS AND METHODS: To
      explore this possibility, we compared the effect on beta- and alpha-cell function
      of transient intensive insulin therapy using lispro versus human regular insulin
      in a total of 21 type 2 diabetic patients who were randomly assigned to 14-days
      intensive insulin therapy consisting of bedtime NPH insulin plus three injections
      of mealtime lispro (n=11) or regular insulin (n=10). The dosages of both types of
      insulin were adjusted to attain preprandial glucose levels of <6.1 mmol/l within
      1 week with similar rates of glucose decline. An oral glucose tolerance test
      (OGTT) was performed at day 0 (baseline), 7, and 14; plasma glucose, serum
      insulin, and plasma glucagon responses over 0-120 minutes were measured, and
      calculated as the area under the curve (AUC). RESULTS: Lispro led to a
      significant reduction in glucose-AUC and also an increase in insulin-AUC versus
      regular insulin on day 7. Glucagon secretion following OGTT was well suppressed
      with lispro on day 14 compared to regular insulin. CONCLUSION: Two-week intensive
      insulin therapy with lispro appeared to be more effective than that with regular
      insulin in type 2 diabetes in attaining both more rapid beta-cell rest and
      greater suppression of glucagon. These changes may provide significant long-term
      benefits.

PMID- 15497511
TI  - The lower pole of the earlobe is an alternative site for painless blood sampling
      in the self-assessment of blood glucose concentrations.
AB  - OBJECTIVES: Measurement of blood glucose is essential for better control of
      diabetes mellitus. The pain associated with repeated blood sampling is a
      significant problem, and a less painful technique would be advantageous. This
      study was conducted to establish a less painful method of blood sampling for
      monitoring of blood glucose concentrations. METHODS: Fourteen healthy doctors and
      nurses at the age of 22 to 32 years were enrolled into this study. The earlobe
      was divided into 20 areas. Each area was punctured with a fine needle and the
      pain was assessed by the visual analog scale (VAS). Then, localized cooling or
      warming was applied before puncture and the pain was assessed by the VAS.
      RESULTS: The VAS tended to be lower toward the lower part of the earlobe. The VAS
      in the uppermost area was 53.1 +/- 19.1 mm and 28.9 +/- 16.8 mm in the lowest
      part of the earlobe. The VAS was higher in the uppermost area than in the lowest
      area in six of the seven volunteers (p=0.028). We did not find significant
      differences in the VAS and blood glucose levels between the control sampling and
      the warming, or cooling sampling. The localized warming shortens the time to
      obtain blood by 4.4 seconds (p=0.0426). CONCLUSION: The area of the ear, but not
      localized cooling or warming, significantly affects the pain in sampling blood
      from the earlobe. Blood sampling for glucose tests are recommended to be obtained
      at the lower pole of the earlobe.

PMID- 15497512
TI  - Pilot study to reduce dioxins in the human body.
AB  - OBJECTIVE: The accumulation of dioxins, characterized by its lipophilicity and
      persistency in human tissue, is a great concern since many of these compounds
      elicit adverse health effects and developmental toxicity. Although the half-life
      of dioxins in the human body have been described to be as long as 3-25 years,
      there are very few drugs or methods that can exclude them from the human body.
      Thus, it is necessary to establish a new method to reduce them and prevent
      adverse health effects. Here, a pilot study to reduce the dioxins accumulated in
      the human body using the cholesterol-lowering drug, colestimide, is reported.
      PATIENTS AND METHODS: Eight male and two female subjects were investigated. All
      of them were treated with colestimide for six months, and the dioxin level of the
      blood samples was assessed before and after the treatment. The dioxins in the
      blood samples were measured by gas-chromatography/mass spectrometry. RESULTS:
      Nine out of the ten subjects completed the treatment, and their blood samples
      were analyzed. The mean dioxin level in the blood samples before the treatment
      was 44.0 +/- 8.22 pg-TEQ/g-fat. Six months later, the mean dioxin level was
      lowered about 20% on average to 34.7 +/- 5.49 pg-TEQ/g-fat. CONCLUSION: Previous
      studies have reported that the blood dioxin level increases with age. In this
      study, the results suggest that colestimide can decrease the blood dioxin level
      of humans. A randomized placebo-controlled clinical study including large numbers
      of subjects are needed to confirm the present result.

PMID- 15497513
TI  - Serial changes of intrathecal viral loads evaluated by chemiluminescence assay
      and nested PCR with aciclovir treatment in herpes simplex virus encephalitis.
AB  - OBJECTIVE: We assessed the potential for estimating the effects of antiviral
      therapy on the clearance of intrathecal herpes simplex virus (HSV) antigens as
      evaluated by the chemiluminescence assay (CL) and on that of intrathecal HSV-DNA
      as evaluated by the nested polymerase chain reaction (PCR) in serial patients
      with herpes simplex virus encephalitis (HSVE). METHODS: The materials comprised
      serial cerebrospinal fluid (CSF) samples from 18 patients with HSVE. All patients
      were diagnosed as having HSVE retrospectively based on the detection of
      intrathecal HSV antigens by the CL, that of HSV-DNA by the nested PCR, and also
      serological confirmation of intrathecal antibody production. The relationships
      between the days of aciclovir therapy and serial HSV viral loads as evaluated by
      the CL and nested PCR in the serial CSFs were assessed. RESULTS: The serial
      intrathecal viral loads evaluated by the CL and nested PCR declined after the
      commencement of aciclovir administration in all patients. The serial alterations
      of the intrathecal viral load evaluated by the CL in each patient were similar to
      those of the intrathecal viral load evaluated by the nested PCR. The initial and
      maximum viral loads evaluated by the CL and nested PCR showed a wide distribution
      in the CSF samples taken from the patients with poor and good outcomes.
      Differences in the means of the viral loads in the CSF samples taken from the
      patients between a poor outcome and a good outcome were not evident. A transient
      increase of viral load as evaluated by these two methods was noted in the same 4
      patients. The viral loads in these 4 patients also declined in the subsequent CSF
      samples. The outcome of these 4 patients was good in one patient and poor in the
      others. CONCLUSION: Evaluation of intrathecal viral antigens by the CL has a
      potential for estimating the effects of antiviral therapy, as does evaluation of
      the intrathecal HSV-DNA by the nested PCR. The intrathecal viral loads evaluated
      by CL and nested PCR were not a predictor of outcome in HSVE.

PMID- 15497514
TI  - Liver transplantation-associated hypercalcemia followed by acute renal
      dysfunction.
AB  - A 34-year-old woman with liver insufficiency due to glycogen storage disease III
      underwent a living spousal liver transplantation. Soon after the successful
      operation, moderate hypercalcemia along with hyperbilirubinemia emerged without
      clarified reasons. The hypercalcemia persisted for over a month despite
      calcitonin treatment and the serum calcium level surged to 13.2 mg/dl with
      albumin correction. Renal dysfunction was indicated by an acute increase in serum
      creatinine (approximately 0.8 to approximately 2.8 mg/ml), which was assumed to
      be hypercalcemia-induced and was effectively treated with bisphosphonate,
      pamidronate (30 mg, i.v.). Recent topics related to transplantation-associated
      hypercalcemia are discussed.

PMID- 15497515
TI  - Domestic infection of hepatitis E in Japan.
AB  - In most cases of hepatitis E in Japan, patients acquire the viral infection
      abroad in countries where hepatitis E is endemic. However, in Nagano Prefecture,
      Japan, we encountered a patient with hepatitis E who had never been abroad. The
      diagnosis was made on finding hepatitis E viral RNA and antibodies against the
      virus in the serum. Prompt normalization of liver function test occurred without
      medication. The nucleotide sequence of the virus isolated from this patient was
      closely related to the sequence of previously isolated viruses of genotype III.
      The source of infection could not be identified.

PMID- 15497516
TI  - Post-operative constrictive pericarditis complicated with lymphocytopenia and
      hypoglobulinemia.
AB  - A 71-year-old man who had a history of open chest surgery was admitted due to
      anasarca and bilateral pleural effusions. Although imaging modalities could not
      demonstrate any pericardial abnormalities, right-sided cardiac catheterization
      revealed 'dip and plateau' in diastolic pressure waveform. He was admitted
      frequently because of the episodic right-sided congestive heart failure and
      hypoproteinemia due to protein-losing enteropathy. The peripheral lymphocyte
      count and serum gamma-globulin concentration were gradually decreased, and
      finally showed lymphocytopenia and hypoglobulinemia. On the last admission, the
      patient showed extensive cellulitis on both legs, and he developed septicemia,
      and finally died due to septic shock. Post-mortem examination showed that both
      visceral and parietal layers of the pericardium adhered tightly with mediastinal
      fibrosis. This case report suggested that constrictive pericarditis should be
      considered even if there is a lack of typical abnormal pericardial imaging
      findings when patients have a history of open chest surgery and recurrent right
      sided congestive heart failure. In addition, we should be aware of a serious
      outcome due to immune compromised conditions such as lymphocytopenia and
      dysglobulinemia in this disorder.

PMID- 15497517
TI  - A patient with classic severe primary hyperparathyroidism in whom both Tc-99m
      MIBI scintigraphy and FDG-PET failed to detect the parathyroid tumor.
AB  - A 24-year-old woman was admitted to our department for further examination of
      hypercalcemia, a high level of intact parathyroid hormone (PTH) and a right
      parathyroid tumor. She complained of bone pain throughout her body and was unable
      to walk due to systemic cystic osteofibrosis, including a brown tumor of the left
      lower extremities. Neck ultrasonography (US) and magnetic resonance imaging (MRI)
      revealed a tumor 2 cm in diameter in the upper side of the right thyroid lobe.
      99mTc sestamibi (99mTc-MIBI) imaging and F-18 fluorodeoxyglucose positron
      emission tomography (FDG-PET) were performed to diagnose primary
      hyperparathyroidism and examination of other parathyroid glands. However, neither
      imaging modality detected the parathyroid tumor. To confirm the diagnosis, we
      performed selective venous sampling around the parathyroid and the patient was
      diagnosed with primary hyperparathyroidism due to a right parathyroid tumor.
      Resection of the right parathyroid tumor was performed and the pathological
      diagnosis was parathyroid adenoma. To date, both 99mTc-MIBI and FDG-PET are
      useful to localize parathyroid tumors. In this case, however, neither modality
      detected the tumor. Although recent studies state that expression of P
      glycoprotein (P-gp) in parathyroid tumors plays an important role in the false
      negative results of both 99mTc-MIBI scans and FDG-PET, immunohistological study
      detected no P-gp expression in the parathyroid tumor in the current case.

PMID- 15497518
TI  - Severe hypoglycemia and hypokalemia in association with liver metastases of
      gastric cancer.
AB  - We report an 80-year-old man who presented with non-islet cell tumor hypoglycemia
      (NICTH) in association with hepatic recurrence of gastric cancer. His serum
      potassium was reduced from 3.9 to 3.1 mmol/l 5 weeks after gastrectomy, and he
      subsequently developed hypoglycemic coma. He was diagnosed as having NICTH
      because of the presence of serum big IGF-II and positive staining for IGF-II in
      gastric cancer cells obtained at surgery. A computed tomography showed multiple
      liver metastases. His hypoglycemia was refractory to steroid therapy. This case
      suggested that NICTH could develop in association with hepatic metastases of
      gastric cancer. Unexpected hypokalemia may be a manifestation of occult NICTH.

PMID- 15497519
TI  - Tracheo-bronchitis associated with Crohn's disease improved on inhaled
      corticotherapy.
AB  - We report a case of tracheo-bronchitis in Crohn's disease. A 23-year-old Japanese
      woman who had been diagnosed with Crohn's disease three years previously was
      hospitalized. She had been suffering from dry cough for one month. Computed
      tomography of the chest revealed marked thickening of the tracheal wall.
      Bronchoscopy showed erythematous and edematous mucosa with diffuse whitish
      granular lesions in the trachea and bronchi. The bronchial biopsy specimens
      showed non-specific inflammatory infiltrates consisting of lymphocytes and plasma
      cells, and hyperplasia of bronchial glands. Inhaled corticotherapy, fluticasone
      propionate 800 microg/day, was effective for both the inflammatory mucosa and
      thickened tracheal wall.

PMID- 15497520
TI  - Chronic bird fancier's lung presenting with acute exacerbation due to use of a
      feather duvet.
AB  - A 67-year-old man was admitted due to fever and exertional dyspnea. He used to
      raise budgerigars and hill mynahs from 1980 to 1988. He was diagnosed as having
      chronic bird fancier's lung (BFL) based on a positive peripheral lymphocyte
      proliferation to pigeon serum in 1994. His disease was stable until 2000. Three
      months before admission he became a daily user of a feather duvet. A chest CT
      showed newly-developed peribronchial ground-glass opacities and preexisting
      honeycombing. Inhalation provocation test was positive. Administration of
      steroids improved his condition. He has been well after refraining from the use
      of the feather duvet.

PMID- 15497521
TI  - Nonspecific interstitial pneumonia with poor prognosis associated with amyopathic
      dermatomyositis.
AB  - Amyopathic dermatomyositis (ADM) is a clinical subtype of dermatomyositis,
      characterized by the lack of motor weakness and the presence of normal muscle
      enzyme levels. ADM is sometimes accompanied by interstitial pneumonia that shows
      a rapid progressive course associated with a poor prognosis. We report a 49-year
      old patient who presented with nonspecific interstitial pneumonia (NSIP)
      associated with ADM. The patient failed to respond to prednisolone and
      immunosuppressive therapy and died. Although idiopathic NSIP is known to have a
      better prognosis, NSIP in ADM could be a fatal disease. Therefore, we should
      appropriately treat interstitial pneumonia in ADM even if it is NSIP.

PMID- 15497522
TI  - Henoch-Schonlein purpura associated with pulmonary Mycobacterium avium
      intracellulare complex.
AB  - A 57-year-old woman presented with bloody sputum and high grade fever. She had
      been treated for Mycobacterium avium-intracellulare complex (MAC). High grade
      fever slightly decreased and bloody sputum disappeared after two weeks, but low
      grade fever persisted. After 3 days of recurrence of bloody sputum, she suddenly
      complained of palpable pururitic lesions on the bilateral lower extremities with
      bilateral gonalgia. Although there are some reports of direct skin lesions due to
      MAC, there are no reports of hypersensitivity vasculitis, Henoch-Schonlein
      purpura, in MAC. It is necessary to consider MAC infection as a potential cause
      of Henoch-Schonlein purpura.

PMID- 15497523
TI  - Noncardiogenic pulmonary edema in low-dose oral methotrexate therapy.
AB  - In the past two decades, low-dose methotrexate (MTX) has been widely used in the
      treatment of rheumatoid arthritis (RA). As adverse effects, various types of
      pulmonary toxicity have been reported with this therapy. We report a case of MTX
      induced noncardiogenic pulmonary edema in a 35-year-old woman. MTX used in high
      dose for anti-cancer therapy is known to cause non-cardiogenic pulmonary edema.
      However, there are no previous reports of noncardiogenic pulmonary edema caused
      by low-dose MTX therapy. This report suggests that patients receiving oral
      weekly, low-dose MTX may be at risk for the development of noncardiogenic
      pulmonary edema.

PMID- 15497524
TI  - Pulmonary nocardiosis with multiple cavitary nodules in a HIV-negative
      immunocompromised patient.
AB  - The radiological manifestations of pulmonary nocardiosis are very diverse, and
      include non-segmental consolidation and pulmonary nodule(s). Cavitary nodules
      most commonly appear in AIDS patients, and are uncommon in non-AIDS patients. We
      report a case of pulmonary nocardiosis with bilateral multiple cavitary nodules
      in a HIV-negative 60-year-old man with nephrotic syndrome who was receiving
      corticosteroid treatment. It is suggested that pulmonary nocardiosis should be
      considered in the differential diagnosis of multiple cavitary nodules on chest
      radiographs, even in non-AIDS immunocompromised patients.

PMID- 15497525
TI  - Pulmonary Mycobacterium avium disease with a solitary pulmonary nodule requiring
      differentiation from recurrence of pulmonary adenocarcinoma.
AB  - A 56-year-old man with a past history of surgical resection of a primary
      pulmonary adenocarcinoma in the right upper lobe was admitted to our hospital
      because of a rapidly increasing solitary nodule (50x30 mm) in the right S5
      followed on the chest computed tomography (CT) for three months. Although we
      suspected recurrence of the pulmonary adenocarcinoma and performed a CT-guided
      lung biopsy, we could not make a definite diagnosis. Therefore, to rule out
      recurrence of the primary pulmonary adenocarcinoma completely, a partial surgical
      resection of the right middle lobe was performed and a caseating epitheloid
      granuloma with acid-fast bacilli was found. As the causative pathogen,
      Mycobacterium avium complex (MAC) disease should be considered in the
      differential diagnosis of a rapidly increasing solitary nodule through this
      peculiar case of pulmonary MAC disease.

PMID- 15497526
TI  - Involvement of the esophagus and stomach as a first manifestation of varicella
      zoster virus infection after allogeneic bone marrow transplantation.
AB  - A 46-year-old man with myeloproliferative disorder received a stem cell
      transplant from an HLA-identical unrelated donor. Eight months status post
      transplantation, during the course of tacrolimus therapy, the patient developed
      severe epigastric pain and fever. FGS findings showed eruptions with blisters in
      the esophagus and ulcers in the stomach. Biopsy specimens revealed acidophilic
      inclusion bodies in the nuclei. Varicella zoster virus (VZV) DNA copies were
      detected in the serum. No skin lesions were observed prior to hospital admission.
      The diagnosis of visceral VZV infection was made and the gastric and esophageal
      lesions were successfully healed with acyclovir (ACV). Severe abdominal pain is
      one of the most important signs of VZV infection for recipients of stem cell
      transplantation.

PMID- 15497527
TI  - Pseudogout showing meningoencephalitic symptoms: crowned dens syndrome.
AB  - We report a 70-year-old man who presented symptoms resembling those of
      meningoencephalitis and who was subsequently diagnosed as having a crowned dens
      syndrome. The patient exhibited severe neck pains, headache, high fever and a
      pain in his knee joints together with symptoms of the central nervous system. The
      patient's cerebrospinal fluid was almost clear and showed no sign of viral
      infection. An analysis of the synovial fluid in the right knee joint revealed
      typical calcium pyrophosphate dehydrate crystal deposition and a diagnosis of
      pseudogout was therefore made. A tomographic examination of the neck showed
      periodontoid calcification. The patient was first treated with non-steroidal anti
      inflammatory drug, but its effect was only minimal. On the other hand, the
      administration of corticosteroid resulted in a dramatic improvement in his
      condition.

PMID- 15497528
TI  - Recurrent small-artery disease in hyperhomocysteinemia: widowers' stroke
      syndrome?
AB  - Hyperhomocysteinemia is thought to cause ischemic strokes. We report two middle
      aged widowers with frequent recurrences of small-artery strokes, two capsular
      infarcts and a thalamic hemorrhage in one patient, and two thalamic and pontine
      infarcts in the other. Blood tests following the final stroke showed
      hyperhomocysteinemia and methylenetetrahydrofolate reductase C677T gene mutation,
      with low concentration of vitamin B6. Multivitamin supplementation normalized
      plasma homocysteine levels in both patients. Hyperhomocysteinemia is treatable;
      therefore, serum homocysteine should be measured as a potential risk factor for
      stroke recurrence in relatively young patients with recurrent small-artery
      infarctions or hemorrhage, especially those with insufficient lifestyle factors.

PMID- 15497529
TI  - Neurosarcoidosis with spinal root pain as the first symptom.
AB  - We report a 60-year-old woman with neurosarcoidosis. She was referred to our
      hospital for examination of the cause of pain in left Th4-6 dermatome. Chest X
      ray and computed tomography (CT) revealed bilateral hilar and mediastinal
      lymphadenopathy, and her serum angiotensin converting enzyme (ACE) level was
      elevated. Histological finding of mediastinal lymph nodes consisted with
      sarcoidosis. Therefore, her pain was thought to be spinal root pain caused by
      neurosarcoidosis. With the administration of prednisolone, her symptom and
      bilateral hilar lymphadenopathy disappeared, and serum ACE level became normal.
      It is important to pay attention to neurosarcoidosis when patients show unknown
      spinal root symptom, although it is rare.

PMID- 15497530
TI  - Rapidly progressed secondary amyloidosis in a patient with mixed connective
      tissue disease.
AB  - A 39-year-old woman with mixed connective tissue disease suddenly developed
      repeated watery diarrhea two years after the onset of the disease. A colonic
      biopsy specimen revealed amyloid A protein deposition and the diagnosis of
      secondary amyloidosis was established. The amyloid deposition disappeared after
      the 8-month course of the treatment with prednisolone and azathioprine. Molecular
      genetic analysis showed the presence of the gamma-allele in her serum amyloid A
      protein 1 gene. This might be associated with the early onset and progression of
      secondary amyloidosis in our case, just like cases reported in rheumatoid
      arthritis.

PMID- 15497531
TI  - Electrocardiographic abnormality of pure posterior myocardial infarction.

PMID- 15497532
TI  - Does violence still occur in the OR?

PMID- 15497533
TI  - Patient positioning.

PMID- 15497535
TI  - Organ procurement from the perspective of perioperative nurses.
AB  - This study explores the essential personal challenges associated with organ
      procurement from the perspective of perioperative nurses experienced with this
      process. Nurses participated in interviews that reflected and provided detailed
      experiential information about their participation in the procurement process.
      Challenges associated with participation included personalizing the event and
      identifying with the donor family members' grief. Reported feelings about
      participation in organ procurement included anger, sadness, and helplessness.

PMID- 15497536
TI  - Experiences with an intraoperative magnetic resonance imaging system in
      neurosurgery.
AB  - Magnetic resonance imaging (MRI) systems are becoming essential intraoperative
      tools in neurosurgery because they provide high-resolution, detailed images. Only
      a few institutions around the world currently have intraoperative MRI
      capabilities. Consequently, the body of knowledge with regard to safety
      procedures in such an environment is fragmented and often institution-specific.
      The components of the MRI system are described in relationship to surgical
      procedures. Perioperative nursing responsibilities are discussed and a case study
      is presented. The article concludes with a discussion about the present
      limitations of intraoperative MRI equipment.

PMID- 15497537
TI  - Kicking it up a notch--successful teaching techniques.
AB  - Leaders in today's ORs face the challenge of preparing nurses to work in highly
      technical and demanding environments. Various programs have evolved to prepare
      nurses to successfully and safely care for perioperative patients. This article
      reviews teaching techniques used in the Inova Learning Network, Falls Church, VA,
      perioperative nurse fellowship program and examines why they are successful.

PMID- 15497538
TI  - Perioperative clinical learning experiences.
AB  - Academic accreditation is valued by professional perioperative nurses, and it can
      be supported with nursing student interactions in the perioperative environment.
      Coherent, logically ordered educational objectives and participation in
      perioperative interventions facilitate student learning and can be used to meet
      academic accreditation standards. This article shows how nursing student learning
      in the perioperative setting can meet course objectives, satisfy academic
      accreditation criteria, and ultimately, improve patient care.

PMID- 15497539
TI  - Shared governance in an integrated health care network.
AB  - The nursing practice model of shared governance is a key strategy for enhancing
      work environments in Magnet hospitals. Shared governance is a dynamic process
      that promotes collaboration, shared decision making, and accountability for
      practice through workforce empowerment. Although the principles of shared
      governance are universal, structure and process generally follow the needs of an
      organization based on its core values, mission, vision, and philosophy. This
      article details the shared governance structure of one health care network.

PMID- 15497540
TI  - Improving staff member satisfaction and productivity through technology.
AB  - In 2000, the Hospital of the University of Pennsylvania, Philadelphia, installed
      a patient flow management system. Staff members embraced the technology, finding
      that it improved communication and quality of patient care, and hospital
      administrators noticed increased productivity and revenue after implementing the
      system. This article offers an overview of the system's benefits as well as
      recommendations for successful technology implementation.

PMID- 15497541
TI  - From handmaiden to right hand--the beginning of World War I.
AB  - As the United States recovered from the War Between the States, unrest was
      brewing in Europe. In 1914, the assassination of the Archduke of Austria-Hungary,
      Franz Ferdinand, and his wife set events in motion that eventually would lead to
      the first World War. During that time, Edith Cavell, a British-born nurse working
      in Belgium, was drawn into events that would lead to her eventual death. She was
      tried, convicted, and executed for her role in helping her countrymen escape
      through the underground.

PMID- 15497542
TI  - Certification--the gold standard.
AB  - The CNOR certification represents professional achievement, excellence in
      practice, and commitment to continuing education. Reasons for becoming certified
      include monetary rewards, personal satisfaction, and recognition from peers and
      other health care providers. This article provides insight into the development
      of the CNOR examination and information about certifying and recertifying.

PMID- 15497543
TI  - Pushing through barriers to advocate for a patient.

PMID- 15497544
TI  - Too tired to work safely?

PMID- 15497546
TI  - Comparison of the thermal effect on clear corneal incisions during
      phacoemulsification with different generation machines.
AB  - BACKGROUND AND OBJECTIVE: Older generation phacoemulsification units are widely
      employed where economics do not permit frequent upgrades. Thermal effects on the
      cornea while performing phacoemulsification with different generation machines
      were evaluated. PATIENTS AND METHODS: The thermal effect on the clear corneal
      incision during uncomplicated phacoemulsification performed by the Series 10,000
      (Alcon Laboratories, Fort Worth, TX) and the Diplomax (Allergan, Irvine, CA)
      machines was clinically evaluated and correlated with the effective
      phacoemulsification time required. The clinical outcome was analyzed with respect
      to wound closure and surgically induced corneal astigmatism. RESULTS: The average
      effective phacoemulsification time required to emulsify a grade IV cataract was
      88.33 +/- 15.81 seconds with the Series 10,000 machine and 61.67 +/- 21.79
      seconds with the Diplomax machine. A grade 2 or more thermal effect was seen in
      19.33% of patients operated on with the Series 10,000 machine and 3.22% of
      patients operated on with the Diplomax machine. The resultant tissue retraction
      affected wound closure and mean surgically induced corneal astigmatism (1.71 +/-
      1.05 D with the Diplomax machine and 2.21 +/- 1.32 D with the Series 10,000
      machine). CONCLUSIONS: Newer generation machines require less phacoemulsification
      power to emulsify hard cataracts, and the clinical outcomes are more favorable.
      Incision burns must be kept in mind when working with older generation
      phacoemulsification machines.

PMID- 15497545
TI  - The smooth surface tunnel porous polyethylene enucleation implant.
AB  - BACKGROUND AND OBJECTIVE: To describe early clinical results with the porous
      polyethylene smooth surface tunnel (SST) enucleation implant. PATIENTS AND
      METHODS: Uncontrolled, prospective interventional case series of patients
      undergoing enucleation with placement of the SST implant. This implant consists
      of a porous polyethylene sphere with a smooth anterior surface containing pre
      drilled tunnels to facilitate direct suturing of the rectus muscles to the
      implant without use of an implant wrap. Postoperatively, socket healing was
      assessed, and prosthesis and socket motility were evaluated by the surgeon using
      an ordinal scale (0 = no motility to 4 = excellent motility). RESULTS: Thirty
      patients received the SST implant, with a mean follow-up of more than 23 months.
      Two cases of exposure occurred and were managed surgically without the need for
      explantation. Mean socket motility was 3.1 on a 0 to 4 ordinal scale, with mean
      prosthesis motility of 2.8. CONCLUSION: The SST implant provides satisfactory
      socket motility and is generally well tolerated in the anophthalmic socket
      without the need for wrapping material.

PMID- 15497547
TI  - Management of magnetic intravitreal foreign bodies in 71 eyes.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the management of a series of eyes with
      magnetic intravitreal foreign bodies. PATIENTS AND METHODS: This retrospective
      review examined consecutive cases of ocular injury associated with intraocular
      foreign bodies; 71 eyes included had a single metallic intraocular foreign body
      (< 5 mm) located in the vitreous cavity removed by external magnet or intraocular
      forceps. Variables included preoperative and postoperative visual acuity, retinal
      break formation, retinal detachment, presence of an afferent pupillary defect,
      intraocular pressure, entrance site, foreign body size, method of extraction, and
      time between occurrence and surgical extraction. RESULTS: Factors predictive of
      good visual outcome (visual acuity > 20/200) were: shortest interval between
      trauma and foreign body extraction, preoperative visual acuity of 20/200 or
      better, and absence of afferent pupillary defect. CONCLUSIONS: In this
      nonrandomized study, good visual results could be obtained in eyes undergoing
      prompt foreign body removal, especially those with good preoperative visual
      acuity and no afferent pupillary defect.

PMID- 15497548
TI  - Prevention of suture knot exposure in posterior chamber intraocular lens
      implantation by 4-point scleral fixation technique.
AB  - BACKGROUND AND OBJECTIVE: The results and complications of posterior chamber
      intraocular lens (IOL) implantation by a 4-point scleral fixation technique are
      described. PATIENTS AND METHODS: Fifty eyes of 47 patients who underwent scleral
      fixated IOL implantation were retrospectively evaluated. Twenty-one (42%) eyes
      had a history of trauma and 29 (58%) eyes had previously undergone cataract
      surgery. In all cases, IOL implantation by 4-point scleral fixation was performed
      and the knots of fixation sutures were rotated and buried in the globe. The IOL
      position was adjusted by suture rotation for best centration. RESULTS: The mean
      follow-up time was 7 +/- 4 months. Four (8%) eyes had minimal corneal edema
      preoperatively. Cystoid macular edema was noted in 2 (6.8%) eyes in the cataract
      surgery group and 8 (38%) eyes in the posttraumatic group. Two (9.5%) eyes in the
      posttraumatic group had atrophic macular changes and 1 (4.7%) had corneal
      scarring, which impaired vision. No complications such as knot exposure, tilting
      of the IOL, decentralization, or endophthalmitis were noted postoperatively.
      Postoperative mean corrected visual acuity was 0.4 +/- 0.3 in the posttraumatic
      group and 0.4 +/- 0.2 in the cataract surgery group. CONCLUSION: The 4-point
      scleral fixation technique resulted in no serious postoperative complications
      such as suture exposure and endophthalmitis. Because the knot can be rotated and
      buried in the globe, knot exposure is less likely to occur. This procedure is
      more effective than other techniques regarding IOL centralization.

PMID- 15497549
TI  - Changing concepts in management of circumscribed choroidal hemangioma: the 2003
      J. Howard Stokes Lecture, Part 1.
AB  - BACKGROUND AND OBJECTIVE: To review trends in the management of circumscribed
      choroidal hemangioma (CCH) and to propose treatment guidelines based on review of
      recent literature and the authors' personal experience with more than 250 METHOD:
      The English-language literature on the management of CCH was reviewed, with
      emphasis on changing concepts in recent years. RESULTS: Xenon arc and argon laser
      photocoagulation and thermotherapy have been used to treat CCH with localized
      retinal detachment, but there has recently been enthusiasm for photodynamic
      therapy (PDT) using fluorescein angiography and optical coherence tomography to
      monitor subretinal fluid and cystoid retinal edema before and after treatment.
      Tumors with extensive retinal detachment have been managed by surgical attempts
      at retinal reattachment followed by photocoagulation or cryotherapy, and more
      recently by radiotherapy. Management currently includes observation, argon laser
      photocoagulation, transpupillary thermotherapy, PDT, and radiotherapy.
      Enucleation may be necessary in rare cases. The goal of treatment should be to
      induce resolution of existing retinal detachment and to improve or stabilize
      visual loss. CONCLUSIONS: There is increasing use of PDT for CCH with localized
      retinal detachment and radiotherapy for CCH with more extensive detachment.
      Although follow-up is short, current methods may achieve better tumor control and
      better visual outcome. However, caution is advised because long-term follow-up is
      still not available.

PMID- 15497550
TI  - A novel high-resolution kinetic method for visual field mapping of scotoma in age
      related macular degeneration.
AB  - BACKGROUND AND OBJECTIVE: To examine a new high-resolution kinetic mapping method
      for scotoma in age-related macular degeneration. PATIENTS AND METHODS: A computer
      based program for kinetic visual field mapping was tested in 10 healthy subjects
      and 14 patients with age-related macular degeneration and fixed preferred retinal
      locus. The stimulus was presented using a back projector on a screen located 40
      cm from the subject. The findings were then compared with static results.
      RESULTS: Control group mapping revealed good congruency with the anatomic blind
      spot. Mapping of the 14 patients with age-related macular degeneration was rapid
      and revealed good accuracy. The average deviation of the mapping border from the
      anatomic scotoma border was no more than 3.1% of the scotoma radius. Static
      mapping of 7 of the patients with age-related macular degeneration was longer and
      revealed lower accuracy. CONCLUSIONS: The proposed method is more rapid,
      accurate, and consistent than static mapping. It allows accurate mapping of
      central scotoma with suprathreshold stimulus, and may be used in the future for
      detecting the early stages of age-related macular degeneration using subthreshold
      stimulus.

PMID- 15497551
TI  - Blood flow studies and serological testing in the diagnostic evaluation of
      glaucoma: a pilot study.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the prevalence of hemodynamically
      significant carotid artery stenosis, peripapillary blood flow, and serologic
      abnormalities in a pilot study among patients with glaucoma. PATIENTS AND
      METHODS: All subjects underwent complete eye examination, standard automated
      perimetry, carotid Doppler ultrasonography, serum laboratory testing, and
      scanning laser Doppler flowmetry (SLDF). Subjects were subdivided into two groups
      based on glaucoma subtype (normal-tension vs primary open-angle glaucoma) and
      severity (mild vs moderate-advanced). RESULTS: Twenty eyes of 20 patients with
      associated glaucomatous visual field loss were enrolled. No significant
      differences in age, gender, intraocular pressure, systemic comorbidity, number of
      antiglaucoma medications, and prior filtration surgery were observed between the
      groups based on the type and severity of glaucoma. The prevalence of clinically
      significant (> 70%) carotid stenosis, mean peripapillary blood flow assessed by
      SLDF, mean erythrocyte sedimentation rate, mean hematocrit, mean hemoglobin, and
      positive FTA-ABS was similar in both groups. Severity of glaucomatous damage as
      determined by visual field mean defect did not correlate with the degree of
      carotid artery stenosis (R2 < 0.0001, P = .99) or peripapillary blood flow
      derived from mean SLDF (R2 = 0.0005, P = .92). CONCLUSION: Data from this pilot
      study demonstrate that the prevalence of hemodynamically significant carotid
      stenosis, peripapillary blood flow, and serologic abnormalities are similar in
      patients with normal-tension and primary open-angle glaucoma, and do not
      correlate with glaucoma severity.

PMID- 15497552
TI  - Feasibility of noninvasive imaging of chorioretinal oxygenation.
AB  - BACKGROUND AND OBJECTIVE: The feasibility of an optical system for noninvasive
      imaging of chorioretinal oxygenation was evaluated. Due to its depth
      discrimination, this optical section imaging technique has potential for
      differential imaging of oxygen tension in the chorioretinal vasculatures.
      MATERIALS AND METHODS: The method consisted of projecting a narrow laser line
      obliquely on the retina after intravenous injection of an oxygen-sensitive probe
      and imaging the phosphorescence emission. Due to the angle between the incident
      laser and imaging path, a phosphorescence optical section image of the retina was
      captured. The phosphorescence intensity was measured in the chorioretinal
      vasculatures. The method was tested in three rats while breathing 10% oxygen, 50%
      oxygen, and room air. RESULTS: On the phosphorescence optical section image,
      vasculatures appeared laterally displaced according to their depth location,
      displaying probe phosphorescence separately in the chorioretinal vasculatures.
      Oxygenation increased in all vasculatures with increased inhaled percent oxygen.
      Oxygenation in the retinal artery was 2.3, 1.9, and 1.6 times oxygenation in the
      retinal vein, capillary, and choroid, respectively. During hypoxia, oxygenation
      decreased by 28%, 18%, 22%, and 14% in the retinal vein, artery, capillary, and
      choroid, respectively. During hyperoxia, oxygenation increased by 30%, 45%, 36%,
      and 28% in the retinal vein, artery, capillary, and choroid, respectively.
      CONCLUSION: The results demonstrate the feasibility of this technique for
      noninvasive and separate imaging of chorioretinal oxygenation and its potential
      for three-dimensional oxygen tension imaging.

PMID- 15497553
TI  - Transpalpebral migration of solid silicone explant in a phthisical globe.
AB  - A rare case of transpalpebral migration of a solid silicone explant associated
      with polymicrobial infection in a pthisical eye is described. The condition
      resolved completely after surgical removal, wound repair, and antibiotic therapy.

PMID- 15497554
TI  - Successful treatment of rhegmatogenous retinal detachment secondary to globe
      perforation during peribulbar injection in a case of sympathetic ophthalmia.
AB  - Rhegmatogenous retinal detachment followed peribulbar injection in a patient with
      preexisting sympathetic ophthalmia. Inadvertent globe perforation resulted in
      subsequent rhegmatogenous retinal detachment. Scleral buckling and pars plana
      vitrectomy reattached the retina. The histopathology of the subretinal fibrotic
      tissue confirmed the diagnosis.

PMID- 15497555
TI  - Treatment of overhanging blebs with frequency-doubled Nd:YAG laser.
AB  - Large overhanging blebs can be associated with various complications (eg,
      overfiltration, endophthalmitis, and dellen formation). Argon laser treatment of
      such blebs has already been described. The authors used frequency-doubled Nd:YAG
      laser in 3 eyes of 3 patients with large filtering blebs. Gentian violet was used
      to stain the bleb surface and enhance the laser absorption. Laser spots were
      applied over the bleb surface. Bleb shrinkage and remodeling was observed in all
      3 eyes. Intraocular pressure remained normal, suggesting that the filtering
      capability of the blebs was maintained.

PMID- 15497556
TI  - Small pupil phacoemulsification using iris sutures: a new method?
AB  - A case is presented in which an alternative surgical method for managing poorly
      dilating pupils preoperatively or intraoperatively was employed. The technique
      uses iris sutures, is simple, safe, easily reproducible, and reversible, and does
      not require new devices for pupil enlargement. This new surgical method is
      appropriate for extracapsular cataract extraction and phacoemulsification or
      posterior segment surgeries, and maintains pupillary appearance and function
      postoperatively. Although other techniques are generally available, this
      technique may be useful in unique situations where other pupil devices or methods
      are not available.

PMID- 15497557
TI  - Purtscher's-like retinopathy in a patient with systemic lupus erythematosus.

PMID- 15497558
TI  - As the pie shrinks, the table manners deteriorate.

PMID- 15497559
TI  - Printed prescriptions law.

PMID- 15497560
TI  - 2004 legislative primaries provide some surprises statewide.

PMID- 15497561
TI  - Workers comp cost containment committee meets; focus on rules to establish fee
      schedule.

PMID- 15497562
TI  - Are you billing and completing the CMS 1500 correctly?

PMID- 15497563
TI  - Taking care of members--update on TennCare and insurance lawsuits.

PMID- 15497564
TI  - Lawsuits.

PMID- 15497565
TI  - Help is available.

PMID- 15497566
TI  - Communication in the medical marriage. Part 1: listening.

PMID- 15497567
TI  - What every doctor should know about long-term care insurance, part I.

PMID- 15497568
TI  - Literacy, medical care, and health status in Tennessee.
AB  - Based on the most recent information, Tennessee is facing an enormous problem
      with literacy and health outcomes. As a result, the healthcare industry is
      vulnerable because of patients' inability to understand and follow a plan of
      treatment. This in part has resulted in poor healthcare and increased costs in
      providing care. By implementing strategies such as those outlined in Table 1,
      strides can be made in improving the healthcare provided to Tennesseans and
      reducing costs associated.

PMID- 15497569
TI  - Specific carbohydrate diet in treatment of inflammatory bowel disease.

PMID- 15497570
TI  - Treating amiodarone-induced thyrotoxicosis with radioactive iodine.
AB  - Amiodarone use in the United States is increasing including a role in advanced
      cardiac life support protocols. There has been a significant increase in
      hypothyroidism, destructive thyroiditis (type II), and iodine-induced
      thyrotoxicosis (type I) with amiodarone. Preexisting thyroid disease and status
      of iodine intake can determine the nature of iodine-induced thyroid disease.
      Treating amiodarone-induced thyrotoxicosis (AIT) may include traditional
      antithyroid agents, glucocorticoids, and surgery. Usually, it is assumed the
      radioactive iodine uptake (RAIU) will be low, and this choice as a treatment
      modality is excluded at the initial visit. We report a satisfactory outcome in a
      patient with AIT using radioactive iodine. The role of radioactive iodine in
      treating AIT is reviewed

PMID- 15497571
TI  - Portrait of mental illness in the media.

PMID- 15497572
TI  - "Mad cow" and prion diseases.

PMID- 15497574
TI  - Under the laptop.

PMID- 15497573
TI  - Obtaining input with urgency.

PMID- 15497575
TI  - Air recirculation: a case study.

PMID- 15497576
TI  - 10 steps to implementing OSH software.
AB  - Properly implementing software is no simple task. Even the best software will
      fail miserably when not implemented properly. You must have the right individuals
      on your project team to increase the odds of success. I have identified the most
      common steps that should be reviewed to avoid typical pitfalls, ensuring the
      project is completed within the budget and timeline agreed to and not only meets
      the technical scope, but is well received by the users. If done properly, the
      entire process should only take a few months, depending on the complexity and
      size of your project.

PMID- 15497577
TI  - Staying in control.

PMID- 15497578
TI  - Employee wellness--and beyond.

PMID- 15497579
TI  - The cost of cardiac arrest in the workplace.
AB  - As documented in this study, 19 percent were found to have a significant risk of
      having a cardiac arrest. The impressive ROI calls out to other organizations that
      cardiac arrest testing is a good use of funds. But more important, yet more
      difficult to define, is the human impact. Cost savings aside, this form of
      testing may be able to offer a greater solution than the reactive measures
      employed to date. If we can reduce cardiac arrest proactively and save
      considerable amounts of money in the meantime, is there any reason not to try?

PMID- 15497580
TI  - Delivering timely safety recognition.

PMID- 15497581
TI  - A morale boost at Saint Alphonsus Regional Medical Center.

PMID- 15497582
TI  - Make it memorable.

PMID- 15497583
TI  - Evacuation preparedness: managing the safety of employees with disabilities.

PMID- 15497584
TI  - It's your business: fire prevention & recovery.

PMID- 15497585
TI  - 'Undeclared' no more.

PMID- 15497586
TI  - Tips for fitting the masses.

PMID- 15497587
TI  - Hand protection: frequently asked questions.

PMID- 15497588
TI  - The winning combination.

PMID- 15497589
TI  - Up to the task.

PMID- 15497590
TI  - A hidden hazard.

PMID- 15497591
TI  - Horizontal fall arrest systems: rigid systems vs. flexible line systems.
AB  - There are many types of flexible and rigid systems on the market, both permanent
      and temporary. This article does not mean to encompass all possible systems or
      hazards and only intends to give an outline of what at a minimum should be
      examined to make an educated purchasing decision. In many instances, the buyer
      will use the same type of horizontal system for all situations. This is a good
      idea in some cases because it will reduce the need for training on a number of
      different systems, reduce system compatibility issues, and may reduce costs for
      installation, supply, and maintenance. This may not be the best idea if the
      hazard areas differ a great deal; as we have illustrated, one system may not
      function for all areas and tasks. The rigid system is typically the best solution
      simply based on the fact the worker won't fall as far as when he is connected to
      a flexible system, because of the elimination of any dynamic sag and horizontal
      energy absorber deployment. In any case, where you stop the worker from falling
      farther, you decrease the chance there may be an incident where the worker is
      injured. From a cost standpoint, flexible fall arrest systems typically are
      cheapest. In the end, safety professionals must balance the cost and
      effectiveness of the system to prevent an injury.

PMID- 15497592
TI  - A 'win-win' for manual material handling.

PMID- 15497593
TI  - An ergonomics turnaround.

PMID- 15497594
TI  - Protection for process industries.

PMID- 15497595
TI  - The gender gap.

PMID- 15497596
TI  - 5 steps to a world-class safety system.

PMID- 15497597
TI  - Really effective training.

PMID- 15497598
TI  - WHO Expert Committee on Biological Standardization.
AB  - This report presents the recommendations of a WHO Expert Committee commissioned
      to coordinate activities leading to the adoption of international recommendations
      for the production and quality control of vaccines and other biologicals and the
      establishment of international biological reference materials. The report starts
      with a discussion of general issues brought to the attention of the Committee and
      provides information on issues relevant to international guidelines,
      recommendations and other matters related to the manufacture and quality control
      of biologicals. This is followed by information on the status and development of
      reference materials for bovine spongiform encephalopathy, various antigens, blood
      products, cytokines, growth factors and endocrinological substances. The second
      part of the report, of particular interest to manufacturers and national control
      authorities, contains sets of recommendations for the production and control of
      poliomyelitis vaccine (oral) and poliomyelitis vaccine (inactivated) and
      guidelines for the production and control of live attenuated Japanese
      encephalitis vaccine. Also included are lists of recommendations and guidelines
      for biological substances used in medicine, and other relevant documents.

PMID- 15497599
TI  - A miracle of hi touch, hi tech!

PMID- 15497600
TI  - Managing disruptive behaviors in an acute medical/surgical service: a strategy
      for success.
AB  - The implementation of a clinical nurse specialist role is an effective strategy
      for managing disruptive patient behaviors and improving staff nurse morale in an
      acute medical/surgical service.

PMID- 15497601
TI  - The effects of meridian exercise on anxiety, depression, and self-esteem of
      female college students in Korea.
AB  - This study examined the effects of meridian exercise on anxiety, depression, and
      self-esteem of female college students in Korea. The effects of meridian exercise
      on anxiety, depression, and self-esteem were statistically significant (t = 
      7.982, P= .000; t= -8.814, P = .000; t = 9.649, P = .000) between the
      experimental and control group.

PMID- 15497602
TI  - A shift in staff relationships.

PMID- 15497603
TI  - The placebo effect and holistic interventions.
AB  - The growing use of holistic interventions in the form of complementary and
      alternative therapies has renewed interest in the placebo effect. A brief history
      of thought on the placebo effect as a nonspecific, bona fide effect and the
      result of meaning making were explored. Case situations illustrate the interplay
      among holistic interventions, the placebo effect, and healing.

PMID- 15497604
TI  - Factors associated with pressure ulcers in adults in acute care hospitals.
AB  - OBJECTIVES: To identify and describe the relationship of factors associated with
      pressure ulcers in adults in acute care hospitals. DESIGN: Cross-sectional
      prevalence studies. SETTING: University teaching hospital. PATIENTS: Prevalence
      studies conducted from 1993 to 1995 with a total of 1992 subjects served as the
      derivation sample and a 1996 prevalence study with 581 subjects served as the
      validation sample. MAIN OUTCOME MEASURES: Pressure ulcers and the Braden risk
      assessment subscale scores. DATA ANALYSIS: Logistic regression analysis was used
      to derive a model that fit the data and performed well at identifying factors
      associated with pressure ulcers. Performance of the model, in terms of
      calibration, was statistically evaluated using the Hosmer-Lemeshow goodness-of
      fit test. The effectiveness of the model, in terms of discrimination, was
      assessed by considering the cut-off values using 2 by 2 classification tables to
      measure the overall percentage of subjects correctly classified in the validation
      sample. MAIN RESULTS: Factors associated with pressure ulcers in adults in acute
      care hospitals were identified as age, male gender, sensory perception, moisture,
      mobility, nutrition, and friction/shear. Three interactions were also found to be
      associated with pressure ulcers; 2 interactions (age and sensory perception and
      moisture and sensory perception) were negatively associated and 1 interaction
      (nutrition and gender/male) was positively associated with pressure ulcers. The
      Hosmer-Lemeshow goodness-of-fit test for the derivation sample (0.76) and the
      validation sample (0.79) indicated that the model was well calibrated and a good
      fit. The overall percentage of subjects correctly classified using the validation
      sample was 88%, indicating that the model performed well. CONCLUSIONS: This study
      enhances the knowledge of the relationship of factors associated with pressure
      ulcers in adults in acute care populations and enhances the use and relative
      importance of particular Braden Scale subscales.

PMID- 15497606
TI  - Botanicals' effect on menopausal symptoms.

PMID- 15497607
TI  - [Hydrogels: properties and application in the technology of drug form. I. The
      characteristic hydrogels].
AB  - The following presentation is a review of literature related to application of
      hydrogels in the technology of modern drug form. The review contains the
      description of physical-chemical properties of hydrogels, such as swelling, water
      structure, sol-gel temperature transitions, tacticity. Each characteristic is
      followed by the description of its application as a therapeutical substance
      carrier. In this review described also examples of polymers used to produce
      stimuli-sensitive hydrogels in response to physiological temperature, pH, present
      of ions in organism fluid, or blood glucose level and external response such as
      electric current, light.

PMID- 15497608
TI  - Effect of some anionic polymers on pH of triethanolamine aqueous solutions.
AB  - One of the suggested approaches in the management and prophylaxis of acne
      involves binding of free fatty acids in the form of soap with alcoholamines. Due
      to a possible irritating effect of alcoholamines associated with a relatively
      high pH of their aqueous solutions, complexation of alcoholamines with acid
      polymers is advocated. Triethanolamine is one of the best recognized
      alcoholamines. It was conventionally neutralized with Carbopols, Eudragits,
      alginic acid and pectin. During neutralization of polymer dispersions with
      triethanolamine, variations in the course of the neutralization curve have been
      observed among individual macromolecular compounds. The pH of 0.1 mol/l
      triethanolamine solution reaches 10.51, while following a complete neutralization
      with anionic polymers, such as Carbopols, Eudragits, alginic acid and pectin, pH
      ranges from 3.88 for systems neutralized with alginic acid to 8.50 for the system
      neutralized with Eudragit S-100. Complexation of triethanolamine with anionic
      polymers decreases its pH, and it is possible to find such pH range in which pH
      of the preparation containing the polymer and triethanolamine will correspond to
      the physiological pH of the skin.

PMID- 15497609
TI  - [Effect of corundum-vancomycin composite on soft tissue reaction].
AB  - The ceramics on the basis of corundum is used for implantation in the form of
      porous and solid materials. The solid form was used to produce tissue
      endoprosthesis while porous form is mainly used to fill in the bone defects. The
      corundum ceramics are also known to be used as coatings for implants in
      orthopedics and dentistry. On the other hand there is still a need to find out
      the new way of treatment of the chronic bone infection, during which the
      traditional way of antibiotics therapy is no more effective. One of the possibly
      solution is to use the different biomaterials as drug carriers and in the bone
      surgery one of the best are porous corundum implants, being themselves of high
      biocompatibility, and additionally containing Vancomycin. The main target of the
      investigation presented in this paper was the comparative assessment of the
      corundum ceramics and its composite containing Vancomycin after implantation into
      back muscle of the total of 15 rats. During the post mortem macroscopic
      assessment in the tissues which surrounded the implants there were no any
      inflammatory neither pathological changes observed. In the microscopic findings,
      in early periods, the observed inflammatory tissue reaction for implants with
      vancomycin was significantly greater what could be explained by the high
      concentration of the antibiotic in the given material. On the basis of the
      results of macroscopic and microscopic findings we can state that the composite
      material of corundum ceramic containing vancomycin is of high compatibility and
      could be regarded as the good drug carrier.

PMID- 15497610
TI  - [The bone reaction to the implantation of the corundum-vancomycin composite].
AB  - Polymethacrylate methylene (PMMA) used as the carrier for antibiotic gentamycin
      (Septopal) shows today very limited effectiveness. Only 24% of the staphylococcus
      strains is still susceptible for it. In 1982 this factor was as high as 97%!
      Because of the growing resistance of different strains of staphylococcus,
      enterococcus and G(-) bacillus for antibiotics in present use, came into being
      the necessity for evaluation of the state-of-the-art antibiotic carrier of the
      new generation, which should be effective to destroy the resistant strains of
      bacteria. The porous corundum ceramics proved to be good material for this
      purpose, specially in use for bone surgery. During the laboratory tests it was
      confirmed that corundum ceramics could be soaked with the different antibiotics
      of the new generations. The bacteriological tests proved that corundum ceramics
      soaked with the Vancomycin show the highest possibly antibacterial activity. On
      the basis of those results we undertook the implantation test on animals. The
      implantation was carried out on 10 rabbits in which the samples of tested ceramic
      with Vancomycin were implanted into femoral bone. The investigation periods were
      set up for 1, 3, 6 and 9 months. On the basis of received results of macroscopic,
      microscopic and radiological findings we can stated that corundum ceramic with
      Vancomycin can be used in the treatment of bone infections.

PMID- 15497611
TI  - Use of mesh fibrous dressing covered with fibrin glue (TachoComb) in hemostasis
      after vascular anastomoses in the groin.
AB  - We present in this paper application of haemostatic device TachoComb onto
      bleeding after vascular anastomosis of dacron vascular prosthesis (branch of
      aortobifemoral or bypass aortofemoral) with common femoral artery in the groin.
      Hemorrhagic complications have influence onto clinical status of operated
      patients. Haemostatic TachoComb dressing was applied at 30 cases and results were
      compared to control group consist of 25 cases, in which gas compresses were
      applied. Mean loss blood in group I with the usage of TachoComb was statistical
      characteristic (p < 0.003) smallest than in group II. Also mean time of
      hemostasis was shortest than in group II (p < 0.01). We proved that use of
      TachoComb limits bleeding from suture line connecting artery with vascular
      prosthesis.

PMID- 15497612
TI  - The otodystrophies: diagnosis and differential diagnosis.
AB  - The imaging evaluation of hearing loss is usually focused on inflammatory
      entities, especially chronic otitis/ cholesteatoma and cerebellopontine angles
      lesions, particularly acoustic tumors. This discussion concerns several
      developmental and acquired entities. The developmental entities referred to as
      the otodystrophies include otosclerosis, Paget's disease, fibrous dysplasia, and
      osteogenisis imperfecta. Otosyphilis and postradiation temporal bone changes are
      also included because of the overlapping imaging appearances.

PMID- 15497613
TI  - An approach to the evaluation of the patient with pulsatile tinnitus with
      emphasis on the anatomy and pathology of the jugular foramen.
AB  - Tinnitus is an extraordinarily common malady. The pulsatile variety is especially
      troublesome to both the patient and physician. In this communication, an overview
      of this frustrating symptom is provided with emphasis on the regional anatomy.

PMID- 15497614
TI  - Lesions of the cerebellopontine angle and internal auditory canal: diagnosis and
      differential diagnosis.
AB  - Schwannoma of the eighth cranial nerve (acoustic neuroma) is, by far, the most
      common cerebellopontine angle lesion. There is, however, a wide variety of
      differential diagnostic possibilities that must be considered when viewing images
      of patients with sensorineural hearing loss (SNHL), vertigo, and dizziness. This
      communication is intended to provide the reader with an approach to this problem.
      Detailed anatomy of the region is also included in this communication.

PMID- 15497615
TI  - An overview of congenital/developmental sensorineural hearing loss with emphasis
      on the vestibular aqueduct syndrome.
AB  - The evaluation of children with congenital/developmental hearing loss has
      undergone substantial transformation in recent years. This communication focuses
      on the most common cause of this type of hearing loss for which there are imaging
      findings: the vestibular aqueduct syndrome. The normal anatomy of the vestibular
      aqueduct is discussed in detail. The cochlear aqueduct with which it is commonly
      confused is also discussed. An overview of other congenital defects and abnormal
      middle/inner ear communications is also included. A brief discussion of cochlear
      implants is also included for completeness.

PMID- 15497616
TI  - Biofeedback treatment for functional anorectal disorders: a comprehensive
      efficacy review.
AB  - This review aimed to critically evaluate the literature on the efficacy of
      biofeedback for functional anorectal disorders, rate these biofeedback
      applications according to established guidelines, and make recommendations for
      this field based on the literature. The Medline and PsychInfo databases were
      searched to obtain all papers published from 1975 to 2003 that included the terms
      "biofeedback" and either "constipation" "pelvic floor dyssynergia" "fecal
      incontinence" or "anorectal pain." Adult and pediatric papers in any language
      were screened. Prospective studies with five or more participants and a
      description of the treatment protocol and outcome were selected for review.
      Seventy-four studies qualified for review: 33 trials on fecal incontinence (FI),
      38 on pelvic floor dyssynergia (PFD) or functional constipation, and 3 on
      anorectal pain. Only 20% of studies were controlled outcome trials. Treatment
      protocols, etiological subgroups studied and outcome measures varied greatly. The
      overall average probability of successful treatment outcome for patients treated
      with biofeedback was 67.2% for functional FI and 62.4% for constipation. There
      were insufficient data to warrant such calculation for anorectal pain. According
      to standard efficacy rating criteria, biofeedback treatment is efficacious for
      functional constipation or PFD in children and probably efficacious in adults;
      probably efficacious for functional FI; and possibly efficacious for anorectal
      pain. Utilizing data from all applicable studies, we found that success rate per
      subject is significantly higher for biofeedback treatment than for standard
      medical care for PFD/functional constipation, and FI (p < .001 for both).
      Biofeedback treatment may therefore be viewed as a valuable adjunct to medical
      management of functional PFD/constipation and incontinence. A number of
      recommendations for future investigations are made based on the review.

PMID- 15497617
TI  - Electrophysiological correlates of vigilance during a continuous performance test
      in healthy adults.
AB  - The present study evaluated patterns of electrophysiological activity associated
      with sustained vigilance in healthy adults. Quantitative electroencephalographs
      (QEEG) were recorded during the performance of a Continuous Performance Test
      (CPT). Participants were divided into low and high vigilance groups based upon
      their reaction time changes between the early and late portions of the CPT.
      Coherence measures were calculated from the QEEG across the baseline, early CPT,
      and late CPT experimental conditions. Participants in the low vigilance group had
      higher baseline and CPT frontal to posterior coherence in the alpha and beta
      bands suggestive of a less vigilant state throughout the entire study.
      Additionally, the low vigilance group had a significantly greater beta 1 band
      coherence drop from baseline to the initial portion of the CPT than the high
      vigilance group. The combined groups had significantly lower amounts of right
      hemisphere frontal to posterior coherence across a number of frequency bands
      throughout all of the phases of the study when compared to the homologous left
      hemisphere sites. These interhemispheric coherence differences are consistent
      with vigilance network theories that implicate the right frontal and parietal
      lobes in the maintenance of sustained attention (M. I. Posner & M. E. Raichle,
      1994).

PMID- 15497618
TI  - The effects of upright and slumped postures on the recall of positive and
      negative thoughts.
AB  - This study assessed whether it was easier to generate positive and negative
      thoughts in either an upright or slumped position. Twenty-four participants, who
      reported no clinical depression or anxiety, completed the Tellegen absorption
      questionnaire and a self-assessment of imagery ability. Surface electromyography
      (sEMG) of zygomaticus major, heart rate, and respiratory rate were assessed
      across four 1-min counterbalanced conditions of either upright or slumped posture
      and either positive or negative thought generation. Posttrial checks of
      compliance were completed. At the end of the study, participants rated which
      thought was easiest to generate in the two postures. Significantly more
      participants (22), or 92%, indicated it was easiest to generate positive thoughts
      in the upright position. ANOVA of sEMG activity significantly distinguished
      positive and negative thoughts in both positions. Significant correlation
      coefficients were observed between scores on the Tellegen scale of absorption and
      the ability to generate thoughts quickly and between self-perceptions of imagery
      ability with the maintenance of thoughts across time. This study supports the
      finding that positive thoughts are more easily recalled in the upright posture.

PMID- 15497619
TI  - Modification of baroreceptor cardiac reflex function by biofeedback.
AB  - Baroreceptor sensitivity (BRS) is considered a powerful prognostic factor in
      cardiovascular health. This study investigated the possibility of modifying the
      baroreflex cardiac function through biofeedback. Thirty-two psychology students
      underwent 3 biofeedback sessions, with four 5-min trials each, in which they had
      to increase and decrease baroreflex function. BRS was assessed by a system that
      analyzed baroreflex cardiac function on-line using a noninvasive spontaneous
      sequence method in the time domain. Baroreceptor parameters were differentiated
      in terms of blood pressure increases ("up" sequences) or blood pressure decreases
      ("down" sequences). BRS in the "up" sequences increased during the Increase
      Condition and decreased during the Decrease Condition. BRS in the "down"
      sequences decreased during the Decrease Condition but was unchanged during the
      Increase Condition. The increase in BRS during the Increase Condition was
      associated with a significant reduction in blood pressure and increase in heart
      period. The opposite cardiovascular changes were observed during the Decrease
      Condition. Suggestions for future research were discussed.

PMID- 15497620
TI  - Hemodynamic changes during long meditation.
AB  - Changes in heart rate (HR) and blood pressure (BP) in advanced male meditators
      during 1 hr of meditation were compared with matched control participants resting
      for 1 hr. Also, changes in HR and BP during 3-hr meditation were analyzed. HR was
      recorded continuously during meditation (n = 38) and the control rest (n = 21).
      BP was measured before and after the meditation (n = 44) and the rest (n = 30).
      During the first hour, HR declined more in the meditators than the controls (p <
      .01). Within participant variability of HR was significantly lower during
      meditation than rest (p < .05). In the second hour of meditation, HR declined
      further (p = .01). BP was unaffected by either meditation or rest. In conclusion,
      meditation reduced the level of HR and within participant variability of HR more
      than rest. HR continued to decline during the second hour of meditation.

PMID- 15497621
TI  - Startle responses in motor vehicle accident survivors: a pilot study.
AB  - The aim of the present study was to investigate startle responses in motor
      vehicle accident (MVA) survivors to trauma-related, startle, and neutral sounds.
      Participants were 17 MVA survivors, 11 of whom participated in a controlled
      treatment study comparing cognitive-behavioral treatment (CBT) and supportive
      therapy (ST) versus a waitlist condition. Though participants differed
      significantly in their pretreatment clinical status and symptom severity, these
      differences were not reflected by group differences in EMG (at orbicularis oculi)
      to the stimuli at the initial assessment. Some cue-specificity was found, as all
      participants showed larger startle responses to trauma-related sounds, compared
      to startle and neutral sounds. At posttreatment, a significant reduction in EMG
      reactivity to all stimuli was observed in participants who received active
      treatment (either CBT or ST), compared to waitlist controls. The use of startle
      responses as a PTSD treatment outcome index is discussed.

PMID- 15497622
TI  - Forensic psychiatry in its time and place.

PMID- 15497623
TI  - Violent adolescents: psychiatry, philosophy, and politics.
AB  - Historically, the American Academy of Psychiatry and the Law (AAPL) has not
      engaged in debates on public policy. In its unique position at the interface of
      law and medicine, AAPL is able to make important contributions to social policy
      involving management of violent youths. In the 1990s, increasing rates of
      violence among adolescents spawned a new era of research into the causes and
      correlates of violence in youths. The resultant data on risk factors have
      provided opportunities for establishing empirical assessments and risk-focused
      treatment programs. Community treatment programs that demonstrate a moderate
      effect in reducing violence have renewed optimism about the benefit of treatment
      over punishment. The ongoing development of methodology to assess risk for
      violence presents opportunities for advancement of rehabilitation. Current social
      policies that limit the ability to provide treatment and rehabilitation in
      juvenile settings should be challenged by organized psychiatry.

PMID- 15497624
TI  - Ethnicity, race, and forensic psychiatry: are we color-blind?
AB  - Race, ethnicity, and culture have an effect on all aspects of mental illness.
      Forensic psychiatrists and psychologists should consider these issues when
      performing evaluations for legal purposes and when providing treatment to the
      special populations with whom they work. This article defines race and ethnicity
      and reviews the available literature on the impact of race and ethnicity on
      diagnosis, dangerousness assessment, involuntary commitment, competency, criminal
      matters, evaluation of children and matters related to them, and tort issues.
      Also discussed is the effect of ethnicity on the role of the forensic evaluator
      in his or her interactions with the subject and the justice system. Forensic
      evaluators are encouraged to develop specific skills related to competency in
      dealing with cultural matters.

PMID- 15497625
TI  - Commentary: racial bias in diagnosis and medication of mentally ill minorities in
      prisons and communities.

PMID- 15497626
TI  - Commentary: ethnicity, race, and forensic psychiatry--is being unblinded enough?

PMID- 15497627
TI  - Commentary: forensic psychiatry--can its pursuit of the truth be color-blind?

PMID- 15497628
TI  - Clergy counselors and confidentiality: a case for scrutiny.
AB  - As religious organizations contribute increasingly to community mental health,
      counseling by clergy acquires greater significance. As a result, clergy confront
      from time to time ethics challenges resulting from the need to balance a
      commitment to clients and an obligation to follow the requirements of religious
      doctrine. The recent New York case of Lightman v. Flaum highlights an example of
      this dilemma. A woman who asked two rabbis (Flaum and Weinberger) for help in her
      marriage complained that they had violated the confidentiality she expected of
      them. The rabbis requested summary judgment based on religious grounds, and the
      trial court rejected their request. The state's highest court concurred with an
      appeal court's reversal of the trial court. We discuss the arguments raised in
      this case about the extent to which clergy may owe a duty of confidentiality to
      those who consult them for psychological help, and we also consider the religion
      based arguments that would fashion an exception to confidentiality in this unique
      context.

PMID- 15497629
TI  - Commentary: clergy confidentiality--a response to Griffith and Young.

PMID- 15497630
TI  - Patterns of spouse and child maltreatment by discharged U.S. Army soldiers.
AB  - The transitional compensation (TC) program of the U.S. Army provides financial
      and other benefits to the families of service members discharged for child or
      spouse maltreatment. We analyzed the TC records of the 347 offenders, 337 spouses
      (160 victims and 177 nonvictims) who were applicants for benefits, and 820
      children (244 victims and 576 nonvictims). One hundred fifty-two spouses were
      physically abused and eight were sexually abused. One hundred eighty-two children
      were sexually abused, 61 were physically abused, and one was emotionally abused.
      The Army Central Registry (ACR) of child and spouse maltreatment cases was
      examined to determine whether the TC offenders and victims had a history of prior
      maltreatment and to assess its severity. Ninety percent of the TC offenders had
      an ACR history as child or spouse maltreatment offenders. Seventy-four percent of
      the TC child abuse victims had an ACR history as victims, and 81 percent of the
      TC spouse abuse victims had such a history. The severity of maltreatment in the
      ACR of TC child and spouse victims was greater than the overall severity of
      maltreatment for those in the ACR database who were not in the TC database. Other
      children in the family who had not been identified as TC victims also had an ACR
      history that was more severe. Health and social service agencies should be aware
      of the TC program and be knowledgeable about its benefits for family members of
      soldiers discharged for abuse-related offenses.

PMID- 15497631
TI  - Culpability for inducing mental states: the insanity defense of Dr. Jekyll.
AB  - Insanity acquittees are often (erroneously) believed to get away with murder.
      This article examines one possible cause of this view--that insanity acquittees
      may have, to various degrees, caused or exacerbated their own mental disorder in
      the first instance. Such a component of prior fault is illustrated with recourse
      to the putative insanity defense of Dr. Jekyll, who, while almost certainly not
      criminally responsible at the time he committed murder (in the guise of Mr.
      Hyde), was culpable for bringing about that nullification of responsibility
      (thereby causing the conditions of his own defense). Such culpability (also found
      in intoxication cases) is examined in relation to medication noncompliance in
      mentally disordered offenders, and possible solutions for dealing with "culpable
      madness" are presented.

PMID- 15497632
TI  - Expert witness perceptions of bias in experts.
AB  - A pilot study of perceptions of different sources of expert bias, as well as of
      personal investment in case outcomes, was performed among attendees at a workshop
      at an annual meeting of the American Academy of Psychiatry and the Law.
      Participants were asked to rate hypothetical responses by experts to various case
      outcomes and the biasing potential of different kinds of situations for opposing
      or other experts. A factor analysis produced two factors. Factor 1 included
      questions about situations that were obviously biasing (such as working only for
      the defense). Factor 2 included questions assessing the potential of certain
      situations to cause bias in experts, or how likely experts thought other experts
      were to be biased. In general, experts identified only four areas to be overtly
      biasing. All occurred within situations in which experts worked only for one or
      the other side of civil or criminal cases. Experts otherwise thought other
      experts were reasonably bias free and well able to compensate for any bias when
      it occurred. The data suggest that experts may deal with bias by turning down
      cases that may cause them personal discomfort.

PMID- 15497633
TI  - Physician reporting of impaired drivers: a new trend in state law?
AB  - The State of Oregon recently enacted legislation that increases physician
      responsibility for reporting medically at-risk drivers. The legislation comes at
      a time when the public is closely scrutinizing the question of the elderly and
      driving and the role of physicians in the reporting of potentially dangerous
      drivers. The evolution of Oregon's law is somewhat unique and offers an
      opportunity to examine what perhaps is to come in other states. The law broadened
      the role of the physician in assessment and reporting of impaired drivers. It
      also opened the door for new tort, that of "negligent failure to report," before
      input from physicians and other health care providers led to important revisions
      in the final statute. Physicians must look to current statutes to guide the
      legislative process in their own states, so that new law aimed at maintaining
      safe highways also preserves the physician-patient relationship and allows for a
      collaborative assessment of driving skill in the physician's office.

PMID- 15497634
TI  - Commentary: driving and psychiatric illness.

PMID- 15497635
TI  - Sell v. U.S.: involuntary medication to restore trial competency--a workable
      standard?
AB  - Competency to Stand Trial (CST) evaluations are common in the U.S. criminal
      justice system. Of those defendants found Incompetent to Stand Trial (IST),
      psychotic disorders are the most common diagnoses, and active psychotic symptoms
      are strongly correlated with impairments in trial-related abilities. If a
      defendant is rendered IST because of psychosis, restoration will be unlikely
      without antipsychotic medication. Last term, in Sell v. U.S., the U.S. Supreme
      Court dealt with medication refusal in the context of competency restoration. The
      Court held that involuntary medication, under certain circumstances, is
      appropriate. This article includes a review of earlier relevant legal decisions
      and an analysis and discussion of the Sell decision.

PMID- 15497636
TI  - Psychotherapy as law enforcement.
AB  - Legal doctrines do not stand still, but instead evolve and tend to grow and to
      spawn what law school academicians fondly term progeny. Tarasoff is no exception.
      In an expanding list of court decisions, psychiatric patients are being convicted
      of crimes by virtue of actions by their psychiatrists or psychotherapists
      purportedly based on the duty to warn. One recent case has featured surreptitious
      evidence-gathering by a psychiatrist, the latest progeny of Tarasoff.

PMID- 15497637
TI  - Commentary: no place to hide.

PMID- 15497638
TI  - American correctional system.

PMID- 15497639
TI  - [Mini-tRNA as a tool for identification of tRNA structural elements responsible
      for aminoacylation].

PMID- 15497640
TI  - [Lipid complexes as carriers for genetic material].

PMID- 15497641
TI  - [Hepatitis delta virus (HDV) ribozymes].

PMID- 15497642
TI  - [Microbial cold shock proteins].

PMID- 15497643
TI  - [Mitochondrial disorders caused by defects in the intergenomic communication].

PMID- 15497644
TI  - [Molecular mechanism of thyroid hormone action].

PMID- 15497645
TI  - [About inteins: their structure, evolution and applications].

PMID- 15497646
TI  - [Endoglycosidases and glycoamidases].

PMID- 15497647
TI  - Physical activity and health in the European Union.

PMID- 15497648
TI  - A life course approach to preventing and treating oral disease.

PMID- 15497649
TI  - Mental health and physical activity in the European Union.
AB  - OBJECTIVES: This article is the 3rd in a series of four that present data about
      physical activity in 15 member states of the European Union collected by the
      Eurobarometer 58.2. On a descriptive level it investigates the relationships
      between physical activity (MET-h/week) and mental health. METHODS: Data were
      collected in 2002 as part of the Eurobarometer by face-to-face interviews. A
      total of 16,230 respondents age 15 years and older were interviewed. Sample sizes
      were about 1,000 respondents in most nations. Mental health was assessed with the
      Mental Health Inventory (MHI-5) and the Energy and Vitality Scale (EVI-scale).
      Physical activity was assessed with the last 7-days short version of the
      International Physical Activity Questionnaire (IPAQ). RESULTS: Across
      sociodemographic subgroups of the populations investigated (age, gender, marital
      status, gross household income, educational status) it was found, that those
      being more physically active had in general a better mental health. In some of
      the 15 nations evidence for a dose-response relationship between physical
      activity and mental health was found, while in others this was not the case.
      CONCLUSION: Results seem to indicate a positive relationship between physical
      activity level and mental health for population subgroups. However, analysis
      found no evidence that this relationship can be characterized as being dose
      response in all nations.

PMID- 15497650
TI  - Perceptions of environmental opportunities for physical activity in the European
      Union.
AB  - OBJECTIVES: This article is the last in a series of four that present data about
      physical activity in 15 member states of the European Union collected by the
      Eurobarometer 58.2. The focus of this article is on the perception of
      environmental opportunities for physical activity across the European Union.
      METHODS: Data were collected in 2002 as part of the Eurobarometer by face-to-face
      interviews. A total of 16,230 respondents age 15 years and older were
      interviewed. Sample sizes ranged about 1,000 respondents in most nations.
      Physical activity was assessed with the last 7-days short version of the
      International Physical Activity Questionnaire (IPAQ). RESULTS: Results indicate
      relationships between the perceptions of environmental opportunities; gross
      household income and physical activity level (in MET-hours/per week) of
      respondents. Respondents who reported lower income and less physical activity had
      also more negative perceptions of environmental opportunities. Across nations,
      respondents in Denmark, the Netherlands, Luxembourg, and Western Germany had the
      highest satisfaction with environmental opportunities for physical activity. In
      some nations, positive correlations between the perception of environmental
      opportunities and physical activity levels could be observed. CONCLUSION: Results
      show variations in the perception of environmental opportunities across the EU.
      Overall, the majority of respondents rated their environmental opportunities for
      physical activity favourable.

PMID- 15497651
TI  - [Personal support and mortality: a cohort analysis of the National Questionnaire
      Survey 1984-86].
AB  - OBJECTIVES: The aim of the study is to investigate the association between
      personal support and mortality experience in Germany. METHODS: Data source is the
      Life Expectancy Survey of the Federal Institute for Population Research
      (Wiesbaden). This study comprises the National Questionnaire Survey of the German
      Cardiovascular Prevention Study (1984-86) and a mortality follow-up (1998).
      Included are 7240 persons with German nationality aged 31-69 years at baseline.
      957 persons (13.2%) died during the observation period from 1984-1998. An
      additive index combining familiy status and number of persons available in
      emergency situations was administered as indicator for social support. The
      multivariate statistical analysis was performed with the cox-regression method.
      RESULTS: Persons with low or very low personal support yielded in both sexes
      significantly higher relative risks for mortality during the 14 years of follow
      up. The relative risks in the regression models including confounding factors for
      low personal support were 1.49 (p < 0.01) in males and 1.67 (p < 0.01) in
      females, and for very low personal support 1.81 (p < 0.05) in males and 2.31 (p <
      0.01) in females. CONCLUSIONS: These results are indicating an increasing
      importance of personal support for the mortality experience in the general
      population.

PMID- 15497652
TI  - Health inequalities in different age groups: the case of type 2-diabetes: a study
      with health insurance and medication data.
AB  - OBJECTIVE: This study investigates social differentials in the prevalence of
      diabetes type 2 in women and men in a health insurance population. It is
      considered whether social gradients are present over different age strata.
      METHODS: Analyses were performed with records obtained from a German statutory
      health insurance comprising 77,294 women (31.8%) and men (68.2%) of at least 20
      years. Occupational status was used as indicator of socio-economic position.
      Individuals with diabetes were identified using information about antidiabetic
      medication or by hospital diagnoses according to ICD9. The analyses were
      performed for the entire insurance population and for different age strata (<40
      yrs /40-55 yrs/ >55 yrs). RESULTS: The analyses revealed considerable social
      differences in diabetes risks. Considering the whole insurance population with
      the highest socio-economic category as reference group, the odds ratio (OR) for
      skilled non-manuals was OR = 2.9, for skilled manuals it was OR = 4.7, and OR =
      5.6 for unskilled and semi-skilled individuals. After stratifying the insurance
      population into three age groups the social gradients were reproduced for each
      stratum, but their magnitudes increased with age. CONCLUSIONS: In the health
      insurance population considered health inequalities with respect to diabetes are
      considerable, and they are persisting after stratification into age groups.

PMID- 15497653
TI  - [Non-reciprocity in close social relationships, depressive symptoms, and poor
      self-rated health].
AB  - OBJECTIVES: Associations of experienced non-reciprocity in close social
      relationships with health are analyzed in a group of middle-aged employed men and
      women using depressive symptoms and self-rated health as indicators. METHODS: Non
      reciprocity is measured by a newly developed questionnaire containing three
      scales: "partnership", "parent-child", and "non-specific close relationships".
      Depressive symptoms are assessed by the German version of the CES-D scale and
      self-rated health by a single widely tested item. The factorial structure of the
      questionnaire measuring non-reciprocity is analyzed. Subsequently, associations
      are explored using logistic regression analyses with age, gender, socio-economic
      status, and social support as control variables. RESULTS: The factorial structure
      of the questionnaire is confirmed. Significantly elevated odds ratios (OR) of
      depressive symptoms are observed in people who experience non-reciprocity
      (partnership OR = 2.97; parent-child OR = 2.70; non-specific OR = 1.84).
      Similarly, the risk of poor self-rated health is significantly elevated in these
      conditions, except for non-specific non-reciprocity. CONCLUSIONS: Based on the
      newly developed measurement consistent associations of non-reciprocity in close
      social relationships with depressive symptoms and poor self-rated health are
      documented.

PMID- 15497654
TI  - Relationship between caries prevalence and fissure sealants among 12-year-old
      German children at three educational strata.
AB  - OBJECTIVES: To investigate the relationship between caries prevalence and fissure
      sealants among 12-year-old German children at three educational levels. METHODS:
      In 1998 a cross-sectional investigation which comprised 60% of the 12-year-old
      children was performed in Heidelberg, Germany. The children attended three types
      of schools: Gymnasium, Hauptschule, and Realschule. The children received a
      dental examination. Teeth with caries experience were recorded according to WHO
      criteria, and teeth with a fissure sealant were also noted. RESULTS: The mean
      number of fissure sealed teeth per child was 2.49 (Gymnasium), 2.31 (Realschule)
      and 1.17 (Hauptschule). In children who attended a Gymnasium the mean DMFT scores
      were the lowest (0.87 in children with fissure sealant and 1.31 in children
      without fissure sealant). The corresponding values for children who attended a
      Realschule were distinctly higher. The highest mean DMFT scores (2.14 and 3.48,
      resp.) were observed in children who attended a Hauptschule. The proportion of
      caries-free children was higher in all three types of school when fissure
      sealants were present. CONCLUSION: In spite of a high prevalence of fissure
      sealants there is an unequal caries experience among 12-year-old children from
      different educational strata. To improve this situation, persons important to
      promotion of dental health should do all their part to ensure that fissure
      sealants are applied to permanent teeth as early as possible, especially when
      children have caries experience in their primary dentition.

PMID- 15497655
TI  - Mechanisms of action of GH.
AB  - The process of growth, which is common to all multicellular organisms, is complex
      and involves the interaction of a multiplicity of factors; despite this, the
      GH/IGF function still maintains its preminence, and, in turn, the same is true
      for all approaches aimed at reducing the consequences of GH/IGF excess. In this
      review paper, we will deal briefly with some aspects of GH/IGF mechanism of
      action which are instrumental to the appreciation of a novel class of a
      "designer" GH antagonist, for use in conditions characterized by excess GH action
      and elevated serum IGF-I.

PMID- 15497656
TI  - Discovery and development of a new class of drugs: GH antagonists.
AB  - In attempting to understand the structure of the GH molecule and its function(s),
      we found that 1 amino acid, glycine, in the third alpha-helix of GH (Gly119 of
      bovine GH and Gly120 of human GH) was important for biologic activity.
      Substitution of this glycine residue with a variety of amino acids resulted in GH
      analogs that lacked growth-promoting activity. More important, these analogs
      inhibited the actions of GH in vitro and in vivo and were classic antagonists. In
      this regard, the in vivo expression of GH-antagonist genes in transgenic mice
      results in dwarf animals that are fertile and have no abnormal phenotypes. The
      mechanism by which the GH antagonists appear to operate is to inhibit proper or
      functional GH-receptor dimerization. GH antagonists may have clinical
      applications when endogenous GH levels are elevated (e.g. acromegaly), or when GH
      action has been implicated in disease states (e.g., cancer- or diabetes-induced
      end-organ damage). A GH-receptor antagonist, pegvisomant, has been developed for
      these clinical situations.

PMID- 15497657
TI  - Hormonal diagnosis of GH hypersecretory states.
AB  - GH hypersecretory states include organic and functional causes. Among functional
      GH hypersecretory states, enhanced somatotroph secretion physiologically occurs
      at birth associated with reduced IGF-I levels reflecting the still immature
      sensitivity of liver to circulating GH levels; this may also occur in women
      exposed to oral extrogens. Pathophysiological conditions of GH hypersecretion are
      generally associated with congenital or acquired/functional conditions of
      peripheral GH insensitivity. Genetic alterations of the GH receptor lead to the
      so called Laron's syndrome. On the other hand, a relevant number of clinical
      conditions (malnutrition, malabsorption, anorexia nervosa, liver cirrhosis, renal
      failure, Type 1 diabetes mellitus) are associated with acquired GH insensitivity
      and a more or less pronounced GH hypersecretion. Both organic and acquired
      conditions of GH insensitivity show low IGF-I synthesis and release and therefore
      lack the negative IGF-I feedback action on somatotroph function. GH
      hypersecretion may be associated with renal failure; however, in this case, the
      alteration in the metabolic clearance rate of GH would also have a role;
      moreover, IGF-I levels are generally normal in this condition. Hyperthyroidism is
      another condition connoted by elevated GH levels that reflects a true GH
      hypersecretory state and is, in fact, associated with high-normal IGF-I levels;
      this peculiar condition is likely to be reflecting the stimulatory effect of
      thyroid hormones on both GH and IGF-I secretion and is promptly reversed by
      treatment-induced euthyroidism. Apart from these "functional" hypersecretory
      state, the classic organic GH hypersecretory state is represented by acromegaly
      or giantism. In these conditions GH hypersecretion is generally sustained by a
      pituitary adenoma hypersecreting GH alone or together with another pituitary
      hormone, mostly PRL; less frequently GH hypersecretion may be due to ectopic GHRH
      hypersection. Exaggerated GH secretion elicits exaggerated IGF-I synthesis and
      secretion that is, in turn, responsible for the large majority of endocrine signs
      and symptoms. In the appropriate clinical context of acromegalic features,
      evidence of concomitant marked GH and IGF-I hypersecretion at baseline
      demonstrates active acromegaly or giantism and indicates the need for magnetic
      resonance imaging in order to verify the presence of a pituitary tumor. However,
      as random measurement of basal GH levels is not reliable for definite diagnosis
      of acromegaly, it is considered mandatory to rely on the lack of GH suppression
      below 1 microg/l during oral glucose tolerance test (OGTT) coupled with elevated
      IGF-I levels. The same criteria are assumed, at present, to define true cure of
      the disease after (or under) treatment. There is consensus about the assumption
      that concomitant normalization or persistent abnormality of both OGTT-induced GH
      nadir and IGF-I levels define a successfully or a poorly controlled disease
      status, respectively. On the other hand, acromegalic patients with GH nadir above
      1 microg/l or IGF-I levels persistently elevated are inadequately controlled and
      their disease should not be considered inactive. It has been clearly demonstrated
      that an extended exposure to GH and IGF-I excess level, even if slight, has a
      very harmful effect on patients; therefore early diagnosis of acromegaly and
      appropriate definition of its cure are of fundamental extreme in order to plan a
      prompt and appropriate therapeutic intervention(s) guaranteed also by the
      continuous improvement in the therapeutic tools available to treat this systemic
      disease.

PMID- 15497658
TI  - Therapy for the syndromes of GH excess.
AB  - This short review summarizes the results of treatments now available in Italy for
      the management of GH and IGF-I excess due to primary pituitary somatotroph
      adenoma, which accounts for over 99% of cases of acromegaly. Goals of treatment
      of acromegaly should now include, in addition to the reduction of tumor bulk and
      symptomatic relief, the lowering of GH circulating concentrations to below a
      critical level (2.5 microg/l, "safe" GH), the normalization of serum IGF-I
      concentrations according to age, improvement (or at least not worsening) of co
      morbidities (diabetes mellitus, hypertension, cardiomyopathy, sleep-apnea), the
      decrease of the risk of premature mortality. Surgery, radiation (fractionated
      conventional radiotherapy and radiosurgery) and medical treatments with dopamine
      agonists and somatostatin analogs are the available options that are discussed in
      detail. The treatment of acromegaly must be tailored to the needs of the
      individual patient. Age, tumor size and invasiveness, GH concentrations, the
      patient's general medical conditions, presence and severity of co-morbidities,
      availability of local resources such as an expert neurosurgeon or gamma-knife
      radiosurgery, and of course the informed wishes of the patient are all factors
      that must be taken into account. For most patients the treatment will be
      multimodal. However, despite criteria and guidelines based on continuously
      emerging information about the management of acromegaly, patient outcomes are
      still less than desirable, with 10 to 20% of patients with uncontrolled disease,
      despite the use of all available therapies. This underscores the need for the
      quick introduction in clinical practice of the new therapies.

PMID- 15497659
TI  - Lessons from 6 years of GH receptor antagonist therapy for acromegaly.
AB  - Pegvisomant is a GH receptor antagonist and a new agent for the medical
      management of acromegaly. The clinical efficacy and safety of pegvisomant in the
      treatment of active acromegaly were demonstrated in a 12-week, placebo-controlled
      trial of 112 patients. After a washout period, patients were randomized to a
      fixed dose of pegvisomant (10, 15 or 20 mg/day) or placebo given by sc injection.
      Serum IGF-I levels were within the normal age-adjusted reference range in 54, 81
      and 89% of patients in the 10-, 15- and 20-mg/day groups, respectively. The
      decrease in serum IGF-I levels was accompanied by considerable improvement in the
      signs and symptoms of active acromegaly. This efficacy profile was maintained in
      a long-term continuation trial, with normalization of serum IGF-I at 12 months
      occurring in 97% of patients. Pegvisomant has been well tolerated with an adverse
      event profile similar to placebo. Two patients had elevations in liver function
      tests that resolved after discontinuing treatment with pegvisomant. During
      treatment with pegvisomant, liver function tests should be monitored on a regular
      basis. Two patients had an increase in pituitary tumor volume during pegvisomant
      therapy; however, the relationship to pegvisomant therapy was not clear. In 131
      patients treated for at least 6 months, there was no increase in mean tumor
      volume, regardless of whether they underwent previous radiotherapy. Pegvisomant
      is an effective new treatment for the management of patients with acromegaly.
      Longer-term data are needed to confirm the safety profile that has been
      demonstrated in studies up to 18 months.

PMID- 15497660
TI  - The use of a GH receptor antagonist in patients with acromegaly resistant to
      somatostatin analogs.
AB  - Pegvisomant, a GH receptor antagonist, is a new pharmaceutical approach to
      acromegaly. It enables IGF-I levels to return in the age- and sex-reference range
      in approximately 90% of patients. This new approach is particularly beneficial in
      those patients who do not experience control of hormone hypersecretion after
      surgery and/or medical treatment with somatostatin analogs. In our preliminary
      experience, out of 16 patients unsuccessfully operated on by transsphenoidal
      surgery and resistant to 40-mg octreotide-LAR or 120-mg lanreotide for at least 6
      months, 13 normalized their IGF-I levels within 6 months from treatment
      beginning. Normalization of IGF-I levels was accompanied by a significant
      decrease of ring size. We did not observe any increase of tumor remnant in this
      short period of treatment. In two cases we observed a significant increase of
      liver transaminases levels. In conclusion, more than 80% of patients with
      acromegaly unsuccessfully treated by surgery or currently available somatostatin
      analogs can achieve normal IGF-I levels after short-term treatment with
      pegvisomant.

PMID- 15497661
TI  - Bioequivalence studies on bisphosphonates: the example of alendronate.
AB  - The study was designed to evaluate the bioequivalence of two formulations of
      alendronate (CAS 121268-17-5, Osalen 10 mg tablets, in the following referred to
      as "test" vs. the originator product, in the following referred to as
      "reference") in 89 healthy male and female volunteers, who were administered four
      10 mg alendronate tablets under fasting conditions. The trial was performed
      according to an open, randomized, cross-over design with a wash-out period of 14
      days in one study center. Urine samples were taken up to 36 h post dose, and the
      concentrations of alendronate were determined by HPLC/Fl method. The mean Ae0-36
      were 102.89 +/- 57.52 microg and 96.23 +/- 60.81 microg for the test and
      reference formulations, respectively, while the mean Rmax were 36.15 +/- 21.07
      microg/h and 35.36 +/- 22.88 microg/h, respectively. The test and reference
      tablets Tmax were 0.592 +/- 0.858 h and 0.583 +/- 0.858 h, respectively. No
      significant differences of pharmacokinetic parameters between the two studied
      formulations were found. The 90% confidence interval for the primary target
      parameters, intra-individual ratios of Ae0-36 and Rmax of alendronate were
      between 1.01 and 1.17 for Ae0-36 and between 0.96 and 1.11 for Rmax, and thus
      within the acceptance range for bioequivalence trials. In the light of the
      present study it can be concluded that alendronate test tablets are bioequivalent
      to the reference formulation.

PMID- 15497662
TI  - Bioequivalence study of atorvastatin tablets.
AB  - The study was designed to evaluate the relative bioavailability of two
      formulations of atorvastatin (CAS 134523-03-8). A bioequivalence study was
      carried out in 24 healthy male volunteers who received four 10 mg tablets of the
      test formulation (Kolestor) and the same dose of the originator product. The
      trial was performed according to an open, crossover design with a wash-out period
      of 7 days in one study center. Blood samples were taken up to 48 h post dose, the
      plasma was separated and the concentrations of atorvastatin were determined by
      HPLC-MS-MS method. The mean Cmax were 16.37 ng/mL and 17.05 ng/mL, while the mean
      AUC0-t were 103.61 ng x h/mL and 102.55 ng x h/mL for the test and reference
      formulations, respectively. The mean AUC0-inf were 118.10 ng x h/mL and 117.13 ng
      x h/mL for the test and reference formulations, respectively. The median tmax was
      0.67 h for both the test tablet and the reference product. The mean t(1/2 el) was
      11.85 h for the test formulation and 13.28 h for the reference formulation. No
      significant differences of pharmacokinetic parameters between the two studied
      formulations were found. The 90% confidence intervals for the primary target
      parameters, intra-individual ratios of AUC0-t and Cmax of atorvastatin, were
      between 0.85 and 1.05 (AUC0-t) and between 0.84 and 1.23 (Cmax), respectively,
      and thus within the acceptance ranges. Concerning the secondary parameter tmax
      the 90% confidence interval for the intra-individual differences was between 
      0.17 and 0.17 h. In the light of the present study it can be concluded that the
      two evaluated atorvastatin formulations, i.e. test formulation of atorvastatin
      and reference preparation are bioequivalent in terms of the rate and extent of
      absorption.

PMID- 15497663
TI  - Assessment of the bioequivalence of different formulations containing
      azithromycin (tablets and suspension).
AB  - Azithromycin (CAS 11772-70-0) is an orally administered macrolide antimicrobial
      drug, structurally related to erythromycin, with a similar spectrum of
      antimicrobial activity. The aim of the present studies, performed in two
      different groups of volunteers, was to compare the bioavailability of
      azithromycin (Azro) 500 mg tablets (study 1) and azithromycin (Azro) 200 mg/5 mL
      suspensions (study 2) with originator products. Each study was conducted
      according to an open, randomized, single-dose, two-period cross-over design in 24
      healthy volunteers with a wash-out period from 14 to 21 days. Blood samples were
      taken up to 96 h post dosing, and concentrations of azithromycin were determined
      by HPLC method. In the first study, the 90% confidence interval for intra
      individual ratios (test vs. reference) of AUC0-t and Cmax of azithromycin were
      between 0.82 and 1.04 for AUC0-t and 0.81 and 1.11 for Cmax, and thus within the
      acceptance ranges for bioequivalence trials. The 90% confidence interval for
      intra-individual ratios of AUC0-t and Cmax of azithromycin administered as
      suspension were between 0.89 and 1.22 and 0.91 and 1.23, respectively. These
      values were also within the acceptance range. Concerning the secondary parameter
      tmax the 90% confidence interval for the intra-individual differences for
      azithromycin were between -0.49 - 0.50 in the first and between -0.50 - 0.25 in
      the second study, respectively. In the light of the results of the studies
      reported here it can be concluded that azithromycin test formulations, i.e.
      tablet and suspension are bioequivalent to the respective reference formulations.

PMID- 15497664
TI  - Studies on the bioequivalence of second generation cephalosporins: cefaclor
      capsules and suspension.
AB  - The aim of the present studies, performed in two different groups of volunteers,
      was to prove the bioequivalence of 500 mg cefaclor (CAS 70356-03-5) test and
      reference capsules (Losefar 500 mg Capsules as test and an originator product as
      reference; study 1) and cefaclor 250 mg/5 mL test and reference suspensions
      (Losefar 250 mg/5 mL Granules oral suspension as test and an originator product
      as reference; study 2). Each study was conducted according to an open,
      randomized, single-dose, two-period cross-over design in healthy volunteers with
      a wash-out period from 7 to 14 days. Blood samples were taken up to 8 h post
      dosing, and concentrations of cefaclor were determined by HPLC method. In the
      first study, the 90% confidence intervals for intra-individual ratios of AUC0-t
      and Cmax of cefaclor were 0.99-1.08 for AUC0-t and 0.82-1.06 for Cmax, and thus
      within the acceptance ranges for bioequivalence trials. The 90% confidence
      interval for intra-individual ratios of AUC0-t and Cmax of cefaclor administered
      as suspensions were 1.10-1.19 and 1.02-1.21, respectively. These values were also
      within the acceptance range. Concerning the secondary parameter tmax the 90%
      confidence interval for the intra-individual differences for cefaclor were
      between -0.13 - 0.13 in the first and between 0.00 - 0.13 in the second study,
      respectively. In the light of the results of the studies reported here it can be
      concluded that cefaclor test formulations, i.e. capsules and suspension are
      bioequivalent to the respective reference formulations.

PMID- 15497665
TI  - Studies on the bioequivalence of different strengths of tablets containing
      clarithromycin.
AB  - The aim of the present studies, performed in two different groups of volunteers,
      was to compare the bioavailability of clarithromycin (CAS 81103-11-9) tablets
      (Klaromin, test tablets) containing 250 mg (study 1) or 500 mg (study 2) of the
      drug with reference tablets of the same strength. Each study was conducted
      according to an open, randomized, single-dose, two-period crossover design in
      healthy volunteers with a wash-out period from 7 to 14 days. Blood samples were
      taken up to 24 h in both studies, and concentrations of clarithromycin and its
      principal active 14-hydroxy metabolite were determined by HPLC method. In the
      first study, the 90% confidence interval for intra-individual ratios of AUC0-t
      and Cmax of clarithromycin were between 0.93 and 1.05 (AUC0-t) as well as between
      0.90 and 1.18 (Cmax). In the second study, i.e. after administration of
      clarithromycin 500 mg tablets, the 90% confidence interval for intra-individual
      ratios of AUC0-t and Cmax of clarithromycin were between 0.90 and 1.08 (AUC0-t)
      as well as between 0.85 and 1.22 (Cmax). All these values were within the
      acceptance ranges for bioequivalence studies. In both studies, the 90% confidence
      interval for intra-individual ratios of AUC0-t and Cmax of 14-hydroxy
      clarithromycin were also within the acceptance ranges, although the confidence
      intervals for these parameters were not planned to be compared with the
      acceptance ranges. In the light of the results of the studies reported here it
      can be concluded that the clarithromycin 250 mg and 500 mg test tablets are
      bioequivalent to the respective reference formulations.

PMID- 15497666
TI  - Clarithromycin suspension: bioequivalence studies on two different strengths.
AB  - Two studies were performed in different groups of volunteers, with the aim to
      prove the bioequivalence of test (Klaromin) and reference clarithromycin (CAS
      81103-11-9) suspensions containing in 5 mL either 125 mg (study 1) or 250 mg
      (study 2) of the drug, administered as an oral dose of 10 mL. Each study was
      conducted according to an open, randomized, single-dose, two-period cross-over
      design in healthy volunteers with a wash-out period from 7 to 14 days. Blood
      samples were taken up to 24 h in both studies, and concentrations of
      clarithromycin and its principal active 14-hydroxy metabolite were determined by
      HPLC. In the first study, the 90% confidence interval for intra-individual ratios
      of AUC0-t and Cmax of clarithromycin were between 0.84 and 1.03 (AUC0-t) and
      between 0.89 and 1.03 (Cmax). In the second study, i.e. after administration of
      clarithromycin suspension 250mg/5mL, the 90% confidence interval for intra
      individual ratios of AUC0-inf and Cmax of clarithromycin were between 1.01 and
      1.17 (AUC0-inf) and between 1.01 and 1.16 (Cmax). All these values were within
      the acceptance ranges for bioequivalence studies. In both studies, the 90%
      confidence interval for intra-individual ratios of AUC0-inf and Cmax of 14
      hydroxy-clarithromycin were also within the acceptance ranges. In the light of
      the results of the studies reported here it can be concluded that the
      clarithromycin test formulations are bioequivalent to the respective reference
      formulations, i.e. suspensions containing 125 mg/5 mL and 250 mg/5 mL of the
      drug.

PMID- 15497667
TI  - Bioequivalence study of clopidogrel bisulfate film-coated tablets.
AB  - The aim of the present study was to evaluate the bioequivalence of two
      clopidogrel (CAS 120202-66-6) formulations. The study was performed according to
      an open, cross-over design in one study center in 36 healthy male and female
      volunteers, comparing a new generic product (tablets containing clopidogrel
      bisulfate, 75 mg) with the originator product (reference). In each of the two
      study periods (separated by a wash-out of 7 days) a single dose of 150 mg (test
      or reference) was administered. Blood samples were taken up to 48 h post dose,
      the plasma was separated and the concentrations of clopidogrel were determined by
      an LC/MS/MS method. AUC0-inf, AUC0-t, Cmax, Tmax and T(1/2 el) were calculated
      for both formulations. The mean AUC0-inf, AUC0-t and Cmax were 29.94 ng x h/mL,
      29.53 ng x h/mL and 7.386 ng/mL, respectively, for the test formulation and 29.24
      ng x h/mL, 28.83 ng x h/mL and 7.921 ng/mL, respectively, for the reference
      formulation. The median Tmax for both formulations was 1.25 h. The point
      estimators of the ratios test/reference formulation for AUC0-inf, AUC0-t and Cmax
      were 101.17%, 101.13% and 90.96%, respectively. Furthermore, the 90% geometric
      confidence intervals of the mean ratio of In-transformed AUC0-inf and AUC0-t were
      narrow and symmetrical around 100%, i.e. from 96.38% to 106.21% for AUC0-inf and
      from 96.20% to 106.30% for AUC0-t, whereas the confidence interval for Cmax was
      84.07% to 98.41%. In can be concluded that the two clopidogrel formulations (test
      formulation of clopidogrel bisulfate and reference formulation) are bioequivalent
      in terms of the rate and extent of absorption.

PMID- 15497668
TI  - Effect of the combination of lisinopril and hydrochlorothiazide on the
      bioequivalence of tablet formulations.
AB  - The aim of the present studies, performed in two different groups of volunteers,
      was to compare the bioavailability of 20 mg lisinopril tablets (Sinopryl as test
      and an orignator product as reference formulation; study 1) and
      lisinopril/hydrochlorothiazide (20 mg/12.5 mg) (CAS 83915-83-7/CAS 58-93-5)
      combined formulations (Sinoretik as test and an originator product as reference
      formulation; study 2). Each study was conducted according to an open, randomized,
      single-dose, two-period cross-over design in healthy volunteers with a wash-out
      period from 7 to 14 days. Blood samples were taken up to 72 h in both studies,
      the plasma was separated. Concentrations of lisinopril and hydrochlorothiazide
      were determined by HPLC-MS-MS method. In the first study, the 90% confidence
      interval for intra-individual ratios of AUC0-t and Cmax of lisinopril were
      between 0.85 and 1.12 (AUC0-t) and between 0.87 and 1.17 (Cmax), and thus within
      the acceptance ranges. In the second study, i.e. after administration of combined
      lisinopril/hydrochlorothiazide formulations, the 90% confidence interval for
      intra-individual ratios of AUC0-inf and Cmax of lisinopril were between 0.83 and
      1.22 (AUC0-inf) and between 0.80 and 1.25 (Cmax). The 90% confidence interval for
      intra-individual ratios of AUC0-inf and Cmax of hydrochlorothiazide were between
      0.92 and 1.04 (AUC0-inf) and between 0.88 and 1.08 (Cmax). All the above values
      were within the acceptance ranges for bioequivalence studies. In the light of the
      present studies it can be concluded that Hsinopril as well as
      lisinopril/hydrochlorothiazide test formulations are bioequivalent to the
      respective reference formulations.

PMID- 15497669
TI  - Combination of losartan and hydrochlorothiazide: in vivo bioequivalence.
AB  - Two trials were performed in different groups of volunteers with the aim to
      compare the bioavailability of 50 mg losartan tablets (Sarvas as test and an
      originator product as reference formulation; study 1) and
      losartan/hydrochlorothiazide (50 mg/12.5 mg) (CAS 124750-99-8/CAS 58-93-5)
      combined formulations (Sarvastan as test and an originator product as reference
      formulation; study 2), respectively. Each study was conducted according to an
      open, randomized, single-dose, two-period cross-over design in 24 healthy
      volunteers with a wash-out period from 7 to 14 days. Blood samples were taken up
      to 36 h in the first study and up to 48 h in the second study. Concentrations of
      losartan and its principal active metabolite, i.e. E3174, as well as
      hydrochlorothiazide were determined by HPLC or LC-MS-MS, respectively. In the
      first study, the 90% confidence interval for intra-individual ratios of AUC0-t
      and Cmax of losartan were between 0.91 and 1.03 (AUC0-t) as well as between 0.87
      and 1.19 (Cmax), and thus within the acceptance ranges. The 90% confidence
      interval for intra-individual ratios of AUC0-t, and Cmax of E3174 were between
      0.90 and 1.13 for AUC0-t, and between 0.97 and 1.14 for Cmax. In the second
      study, i.e. after administration of combined losartan/hydrochlorothiazide
      formulations, the 90% confidence interval for intra-individual ratios of AUC0-t
      and Cmax of losartan were between 0.90 and 1.04 (AUC0-t) as well as between 0.86
      and 1.20 (Cmax). Similarly to the parent compound, no significant differences of
      bioavailability parameters of E3174 between the two studied formulations were
      found. The 90% confidence interval for intra-individual ratios of AUC0-t and Cmax
      of hydrochlorothiazide were between 0.89 and 0.98 (AUC0-t) as well as between
      0.82 and 1.00 (Cmax). In the light of the present studies it can be concluded
      that the losartan as well as losartan/hydrochlorothiazide test formulations are
      bioequivalent to the respective reference formulations.

PMID- 15497670
TI  - In vivo bioequivalence of oral antidiabetic agents: pioglitazone tablets.
AB  - The study was designed to evaluate the bioequivalence of two pioglitazone (CAS
      112529-15-4) formulations. The trial was performed in 26 healthy male volunteers
      with the aim of comparing a new generic product (tablets containing 30 mg pioglit
      azone hydrochloride, test) with the originator product (reference). The trial was
      performed according to an open, crossover design in one study centre. In each of
      the two study periods (separated by a wash-out of 14 days) a single oral dose of
      30 mg (test or reference) formulation was administered. Blood samples were taken
      up to 120 h post dose, the plasma was separated and the concentrations of
      pioglitazone and its principal active metabolite hydroxypioglitazone were
      determined by LC-MS-MS method. AUC0-inf, AUC0-t, Cmax, and Tmax were calculated
      for both formulations. The mean Cmax of pioglitazone ranged between 1.01
      microg/mL and 1.05 microg/mL, while the mean AUC0-inf and AUC0-t ranged between
      10.89 microg x h/mL and 10.98 microg x h/mL as well as between 10.56 microg x
      h/mL and 10.62 microg x h/mL for the test and reference formulations,
      respectively. The median Tmax for the test tablets was 1.50 h and for the
      reference was 1.75 h. The ratios test/reference formulation for AUC0-inf, AUC0-t
      and Cmax were 99.70%, 100.13% and 99.17%, respectively. Furthermore, the 90%
      geometric confidence intervals of the mean ratio of In-transformed AUC0-inf were
      narrow and symmetrical around 100%, i.e. 90.59% to 109.72%, for AUC0-t, 90.69% to
      110.55%, whereas for Cmax they were 87.52% to 112.37%. As in the case of
      pioglitazone, mean values of the principal bioequivalence parameters of
      hydroxypioglitazone did not differ significantly after administration of the test
      and reference formulations. In the light of the present study it can be concluded
      that the two evaluated pioglitazone formulations, i.e. test formulation of
      pioglitazone hydrochloride and reference formulation, are bioequivalent in terms
      of the rate and extent of absorption.

PMID- 15497671
TI  - Bioequivalence study of rofecoxib tablets.
AB  - The study was designed to evaluate the bioavailability of two rofecoxib (CAS
      162011-90-7) tablet formulations. Twenty-four healthy male volunteers were
      administered a 25 mg tablet of the test formulation (Ecrox) containing rofecoxib
      or the originator product (reference). The trial was performed according to an
      open, cross-over design with a wash-out period of 7 days. Blood samples were
      taken up to 72 h post dose, the plasma was separated and the concentrations of
      rofecoxib were determined by an HPLC method. The mean Cmax were 192.07 ng/mL and
      187.35 ng/mL, while the mean AUC0-t were 3613.84 ng x h/mL and 3501.56 ng x h/mL
      for the test and reference formulations, respectively. The median tmax was 3.75 h
      for the test tablet and 4.00 h for the reference formulation. The mean t(1/2 el)
      was 10.66 h and 10.61 h for the test and reference formulation, respectively.
      Mean MRT values for the test and reference tablets were 15.34 h and 15.33 h,
      respectively. Mean MRT values for the test and reference tablets were 15.34 h and
      15.33 h, respectively. No significant differences of pharmacokinetic parameters
      between the two studied formulations were found. The 90% confidence interval for
      the primary target parameters, i.e. intra-individual ratios of AUC0-t and Cmax of
      rofecoxib were between 0.99 and 1.10 (AUC0-t) as well as between 0.96 and 1.10
      (Cmax) and thus within the acceptance ranges. Concerning the secondary parameter
      tmax the 90% confidence interval for the intra-individual differences was between
      -0.25 and 0.25 h. In the light of the present study it can be concluded that the
      two evaluated rofecoxib formulations, i.e. test tablets of rofecoxib and a
      reference preparation are bioequivalent in terms of the rate and extent of
      absorption.

PMID- 15497672
TI  - Serotonin reuptake inhibitors: bioequivalence of sertraline capsules.
AB  - The study was designed to evaluate the bioavailability of two sertraline (CAS
      79617-96-2) formulations. A bioequivalence study was carried out in 24 healthy
      male volunteers, who were administered 50 mg capsules of the test formulation
      (Seralin) and the originator product (reference) as a single dose. The trial was
      performed according to an open, randomized, cross-over design with a washout
      period of 14-20 days in one study center. Blood samples were taken up to 96 h
      post dose, the plasma was separated and the concentrations of sertraline were
      determined by HPLC-MS-MS. The mean Cmax were 9.01 +/- 2.26 ng/mL and 8.24 +/-
      2.14 ng/mL, while the mean AUC0-t were 259.09 +/- 105.36 ng x h/mL and 234.36 +/-
      95.18 ng x h/mL for the test and reference formulations, respectively. The mean
      AUC0-inf were 292.66 +/- 128.09 ng x h/mL (test) and 267.23 +/- 116.40 ng x h/ mL
      (reference). The mean tmax was 5.88 +/- 1.03 h for the test capsules and 6.17 +/-
      1.66 h for the reference formula. The mean t1/2el was 26.49 +/- 6.45 h for the
      test formulation and 26.23 +/- 6.64 h for the reference formulation. Mean MRT
      values for the test and reference formulations were 28.14 +/- 5.37 h and 27.81 +/
      5.13 h, respectively. No significant differences of pharmacokinetic parameters
      between the two studied formulations were found. The 90% confidence interval for
      the primary target parameters, intra-individual ratios of AUC0-t and Cmax of
      sertraline were between 1.03 and 1.19 (AUC0-t) as well as between 1.02 and 1.17
      (Cmax) and thus within the acceptance ranges for bioequivalence trials.
      Concerning the secondary parameter tmax the 90% confidence interval for the intra
      individual differences was between -1.00 and 0.50 h. In the light of the present
      study it can be concluded that sertraline test capsules are bioequivalent to the
      reference formulation.

PMID- 15497673
TI  - Effect of the formulation on the bioequivalence of sultamicillin: tablets and
      suspension.
AB  - Sultamicillin (CAS 76497-13-7) is a pro-drug of a combination of ampicillin and
      sulbactam linked as a double ester. The aim of the present studies, performed in
      two different groups of volunteers, was to compare the bioavailability of 750 mg
      sultamicillin tablets (Duobaktam 750 mg tablets, study 1) and sultamicillin 250
      mg/5mL suspensions (Duobaktam 250 mg/5mL, study 2). Each study was conducted
      according to an open, randomized, single-dose, two-period cross-over design in 24
      healthy volunteers with a wash-out period from 7 to 14 days. Blood samples were
      taken up to 12 h post dosing, and concentrations of ampicillin and sulbactam were
      determined by a HPLC-UV method. In the first study, the 90% confidence interval
      for intra-individual ratios of AUC0-t and Cmax of ampicillin and sulbactam were
      between 1.01-1.18 and 0.95-1.09 (AUC0-t) as well as between 0.87-1.04 and 0.80
      0.96 (Cmax), respectively, and thus within the acceptance ranges. The 90%
      confidence interval for intra-individual ratios of AUC0-t and Cmax of
      sultamicillin suspensions (2nd study) were between 0.94-1.16 (ampicillin) and
      0.92-1.14 (sulbactam) for AUC0-t and between 0.96-1.23 (ampicillin) and 0.97-1.24
      (sulbactam) for Cmax. These values were also within the acceptance range for
      bioequivalence studies. Concerning the secondary parameter tmax the 90%
      confidence interval for the intra-individual differences for both ampicillin and
      sulbactam were between 0.00-0.50 in the first and between -0.17-0.00 in the
      second study, respectively. In the light of the present studies it can be
      concluded that the sultamicillin test formulations, i.e. tablet and suspension
      are bioequivalent to the respective reference formulations.

PMID- 15497674
TI  - Novel approaches to vaccine delivery.
AB  - Although the currently available vaccines represent an outstanding success story
      in modern medicine and have had a dramatic effect on morbidity and mortality
      worldwide, it is clear that improvements are required in the current vaccine
      delivery technologies. Improvements are required to enable the successful
      development of vaccines against infectious diseases that have so far proven
      difficult to control with conventional approaches. Improvements may include the
      addition of novel injectable adjuvants or the use of novel routes of delivery,
      including mucosal immunization. Mucosal delivery may be required to provide
      protection against pathogens that infect at mucosal sites, including sexually
      transmitted diseases. Alternatively, novel approaches to delivery, including
      mucosal administration, may be used to improve compliance for existing vaccines.
      Of particular interest for safer mass immunization campaigns are needle-free
      delivery devices, which would avoid problems due to needle re-use in many parts
      of the world and would avoid needle-stick injuries.

PMID- 15497675
TI  - Peroxisome proliferator-activated receptor (PPAR)-alpha: a pharmacological target
      with a promising future.
AB  - Peroxisome proliferator-activated receptor (PPAR)-alpha is a ligand-activated
      transcriptional factor that belongs to the family of nuclear receptors. PPAR
      alpha regulates the expression of genes involved in fatty acid beta-oxidation and
      is a major regulator of energy homeostasis. Fibrates are PPAR-alpha agonists and
      have been used to treat dyslipidemia for several decades because of their
      triglyceride (TG) lowering and high-density lipoprotein cholesterol (HDL-C)
      elevating effects. More recent research has demonstrated anti-inflammatory and
      anti-thrombotic actions of PPAR-alpha agonists in the vessel wall as well. Thus,
      PPAR-alpha agonists decrease the progression of atherosclerosis by modulating
      metabolic risk factors and by their anti-inflammatory actions on the level of the
      vascular wall. This is confirmed by several clinical studies, in which fibrates
      have shown to reduce atherosclerotic plaque formation and the event rate of
      coronary heart disease (CHD), especially in patients suffering from metabolic
      syndrome (MS). MS is characterized by a group of metabolic risk factors that
      include obesity, raised blood pressure, dyslipidemia, insulin resistance or
      glucose intolerance, and a prothrombotic state, and its incidence in the Western
      world is rising to epidemic proportions. This review paper will focus on the
      functions of PPAR-alpha in fatty acid beta-oxidation, lipid metabolism, and
      vascular inflammation. Furthermore, PPAR-alpha genetics, the clinical use of PPAR
      alpha activators and their future perspective will be discussed.

PMID- 15497676
TI  - An automated method for the determination of montelukast in human plasma using
      dual-column HPLC analysis and peak height summation of the parent compound and
      its photodegradation product.
AB  - PURPOSE: To develop an assay to evaluate the bioequivalence of overcoated and
      marketed montelukast formulations, the former to be used for future blinded
      clinical studies. METHODS: The method used automated 96-well sample preparation
      and dual-column HPLC analysis for increased throughput. Regression analysis was
      performed using the total peak height of montelukast and its photodegradent, a
      cis-ethenyl geometric isomer. This approach successfully compensated for
      montelukast's light sensitivity, allowing both clinical specimen handling and
      bioanalytical laboratory analysis to be conducted without extensive precautions
      being taken to protect samples from UV light. To ensure a molar equivalent
      fluorescence response between the cis (Z) and trans (E) isomers, the emission
      wavelength and detector attenuation were both increased just prior to the elution
      of the montelukast peak (i.e., the trans isomer), effectively dampening the
      response of the stronger fluorophore. Plasma proteins were precipitated using
      acetonitrile, and 50 microl of supernatant was injected onto an HPLC system
      consisting of two C18 analytical columns connected to a 10-port switching valve.
      Injections were overlapped on alternating columns allowing twice as many samples
      to be processed during each analytical run. RESULTS: The calibration curve was
      linear from 5 to 2000 ng ml(-1). The inter-day and intra-day precision expressed
      as coefficient of variation (%CV), were 1.1-6.1% and 3.1-6.7%, respectively. The
      accuracy, reported as percentage bias, was less than or equal to +/-9.1%. The
      absolute recovery was determined to be 94.3% and 98.1% at 15 and 1500 ng ml(-1),
      respectively. CONCLUSIONS: This assay represents a rapid, accurate, and sensitive
      method for the determination of montelukast in human plasma. The method has been
      successfully used to demonstrate the bioequivalence of the overcoated montelukast
      formulations to their equivalent marketed tablets.

PMID- 15497677
TI  - Insulin nanoparticles: a novel formulation approach for poorly water soluble Zn
      insulin.
AB  - PURPOSE: To determine the feasibility of using wet milling technology to
      formulate poorly water soluble zinc-insulin as a stable, biologically active,
      nanoparticulate dispersion. METHODS: The feasibility of formulating zinc-insulin
      as a nanoparticulate dispersion using wet milling technology was studied. An
      insulin nanoparticulate formulation was reproducibly obtained after milling zinc
      insulin in the presence of F68, sodium deoxycholate and water at neutral pH. The
      physical and chemical properties of these peptide particles were studied using
      electron microscopy, laser light scattering, HPLC and SDS-PAGE. To verify
      efficacy, hyperglycemic rats were dosed subcutaneously and intraduodenally with
      nanoparticles or solubilized insulin. Glucose and insulin levels were monitored
      on blood samples collected throughout the study. RESULTS: Zn-insulin (mean size =
      16.162 microm) was processed using milling technology to form an aqueous-based
      nanoparticle dispersion with a mean particle size of less than 0.150 microm. The
      formulation was homogeneous and exhibited a unimodal particle size distribution
      profile using laser light diffraction techniques. Insulin, processed as a peptide
      particle dispersion, was shown to be comparable to unprocessed powder using HPLC
      and SDS-PAGE. In addition, HPLC analyses performed on samples, heat-treated at 70
      degrees C for 100 minutes, demonstrate that under conditions which effect the
      solubilized peptide, formulated as a peptide-particle dispersion, insulin was
      chemically stable. Also, when stored refrigerated, the insulin dispersion was
      chemically and physically stable. Finally, peptide particles of insulin, dosed
      subcutaneously and intraduodenally, were effective at lowering blood glucose
      levels of hyperglycemic rats. CONCLUSION: Water insoluble Zn-insulin can be
      formulated as a stable, biologically active nanometer-sized peptide particle
      dispersion using wet media milling technology.

PMID- 15497678
TI  - The use of inverse phase gas chromatography to study the glass transition
      temperature of a powder surface.
AB  - PURPOSE: To measure the glass transition temperature (Tg) at the surface of a
      hydrophobic particle at different temperatures and humidities, on the hypothesis
      that the surface may be plasticized to a different extent to the bulk due to slow
      water sorption giving a concentration gradient of water through the particles.
      METHODS: Amorphous indomethacin was exposed to a range of relative humidities
      (RH) and temperatures in an inverse gas chromatograph (IGC). The retention
      volumes of decane were calculated at all conditions using center of mass (Vcom)
      and peak height (Vmax) methods. The extent of water sorption was determined
      gravimetrically. RESULTS: The Vcom retention volumes were found to deviate from
      Vmax results at certain critical humidities at each temperature. This was taken
      as a novel method for determining the Tg of the sample surface at different
      experimental conditions. Extrapolating the critical RH to lower the Tg to
      experimental temperature to 0% RH yeilded a Tg similar to literature values.
      Water sorption data provided valuable information on changes in mobility of the
      amorphous form as a function of temperature and RH. CONCLUSIONS: It is possible
      to use IGC to determine the Tg of the surface of particles at defined conditions.
      This overcomes the problems of conventional methods of assessing Tg, relating to
      disruption of water sorption on heating. This helps in the understanding of the
      physical form of the surface of hydrophobic particles and how and when the
      surface will start to crystallize.

PMID- 15497679
TI  - Influence of 5-fluorouracil-loaded microsphere formulation on efficient rat
      glioma radiosensitization.
AB  - PURPOSE: To determine (i) the efficiency of radiosensitizing 5-FU-loaded
      microspheres and (ii) the impact of microparticle formulation on response to
      treatment. METHODS: C6 tumor-bearing rats were stereotactically implanted with
      microspheres and/or allocated to: control groups (untreated) or treatment (only
      radiotherapy; fast-release 5-FU microspheres + radiotherapy; slow-release 5-FU
      microspheres + radiotherapy). The next day, fractionated radiotherapy, limited to
      the hemibrain, was initiated in all treated animals. The irradiation cycle
      included 36 Gy, given in 9 sessions for 3 consecutive weeks. Tumor development
      was assessed by T2-weighted MRI. RESULTS: 5-FU microspheres associated with
      radiotherapy caused a 47% complete remission rate (9/19) as opposed to the 8%
      rate (1/12) when radiotherapy alone or 0% in control animals. Drug delivery for 3
      weeks produced better survival results (57%) compared to one-week sustained
      release (41%). MR images showed exponentially increasing tumor volumes during the
      first half of the radiotherapy cycle, followed by a decrease, and the
      disappearance of the tumor if survival exceeded 120 days. CONCLUSIONS: 5-FU
      controlled delivery is a promising strategy for radiosensitizing gliomas. Drug
      delivery system formulation is unambiguously implicated in both the response to
      treatment and the limitation of toxic side effects.

PMID- 15497680
TI  - Heat-treated Fungizone retains amphotericin B antifungal activity without renal
      toxicity in rats infected with Aspergillus fumigatus.
AB  - PURPOSE: The purpose of this study was to assess the antifungal activity and
      renal and hepatic toxicity of amphotericin B (AmpB) following administration of
      Fungizone (FZ) and a heat-treated form of FZ (HFZ) to rats infected with
      Aspergillus fumigatus. METHODS: Infected rats were administered FZ and HFZ at a
      dosing regimen of 1 mg/kg i.v. once daily for 4 consecutive days. Following
      administration the number of colony forming units (CFUs) of Aspergillus fumigatus
      in different organs and serum creatinine concentrations were determined. RESULTS:
      FZ and HFZ had similar overall effectiveness in decreasing the total number of
      Aspergillus fumigatus CFUs found in all organs analyzed compared to controls.
      Except for the serum creatinine concentrations reported in the nontreated
      infected control rats, none of the treatment groups tested displayed a greater
      than 50% increase in serum creatinine. CONCLUSIONS: Taken together, these
      findings suggest that HFZ at 1 mg/kg once daily x 4 days appears to be as
      effective as FZ as an antifungal agent without renal toxicity.

PMID- 15497681
TI  - Identification of biowaivers among Class II drugs: theoretical justification and
      practical examples.
AB  - PURPOSE: To set up a theoretical basis for identifying biowaivers among Class II
      drugs and apply the methodology developed to nonsteroidal anti-inflammatory drugs
      (NSAIDs). METHODS: The dynamics of the two consecutive drug processes dissolution
      and wall permeation are considered in the time domain of the physiologic transit
      time using a tube model of the intestinal lumen. The model considers constant
      permeability along the intestines, a plug flow fluid with the suspended particles
      moving with the fluid, and dissolution in the small particle limit. The
      fundamental differential equation of drug dissolution-uptake in the intestines is
      expressed in terms of the fraction of dose dissolved. RESULTS: The fundamental
      parameters, which define oral drug absorption in humans resulting from this
      analysis, are i) the formulation-related factors, dose, particle radius size, and
      ii) the drug-related properties, dimensionless solubility/dose ratio (1/q), and
      effective permeability. Plots of dose as a function of (1/q) for various particle
      sizes unveil the specific values of these meaningful parameters, which ensure
      complete absorption for Class II drugs [(1/q) < 1]. A set of NSAIDs were used to
      illustrate the application of the approach in identifying biowaivers among the
      NSAIDs. CONCLUSIONS: The underlying reason for a region of fully absorbed drugs
      in Class II originates from the dynamic character of the dissolution-uptake
      processes. The dynamic character of the approach developed allows identification
      of biowaivers among Class II drugs. Several biowaivers among the NSAIDs were
      identified using solubility data at pH 5.0 and in fed-state-simulated intestinal
      fluid at pH 5.0. The relationships of formulation parameters, dose, particle
      radius, and the drug properties, dimensionless solubility/dose ratio (1/q), and
      permeability with the fraction of dose absorbed for drugs with low 1/q values
      [(1/q) < 1] can be used as guidance for the formulation scientist in the
      development phase.

PMID- 15497682
TI  - Design and evaluation of an emulsion vehicle for paclitaxel. I. Physicochemical
      properties and plasma stability.
AB  - PURPOSE: The current formulation of paclitaxel contains ethanol and Cremophor EL
      and has been reported to cause serious adverse reactions. The purpose of the
      present work was to develop an improved emulsion vehicle for paclitaxel and to
      study the physicochemical properties of such a system. METHODS: Emulsions were
      prepared by either microfluidization or sonication method and the droplet size
      characterized by dynamic light scattering and light microscopy. RESULTS: Stable
      emulsions could be made using mixtures of lecithin/sodium deoxycholate as the
      emulsifiers. The formulation was further improved by using a combination of free
      acid and the sodium salt. Paclitaxel could be loaded into the emulsions at 2.5
      mg/ml without the formation of drug crystals. While these emulsions were stable
      on storage, they flocculated when mixed with plasma. Steric stabilization of the
      emulsion droplets with poloxamer 188 increased the stability of the emulsions in
      plasma but promoted the crystallization of paclitaxel. The crystallization
      tendency could be reduced by using PEG5000PE (1,2-dipalmitoyl-sn-glycero-3
      phosphoethanolamine-N-[poly (ethylene glycol) 5000]), a less water-soluble
      stabilizer. CONCLUSIONS: Emulsions with good stability characteristics containing
      2.5 mg/ml paclitaxel could be made using bile salt/acid and lecithin, and the
      excellent stability of these emulsions in plasma was achieved by steric
      stabilization using PEG5000PE.

PMID- 15497683
TI  - Biodegradable self-assembling PEG-copolymer as vehicle for poorly water-soluble
      drugs.
AB  - PURPOSE: To develop self-assembling systems increasing the solubility of poorly
      water-soluble drugs. METHODS: Low molecular weight liquid biodegradable
      copolymers were synthesized by ring-opening polymerization using caprolactone
      (CAP) and trimethylenecarbonate (TMC) as monomers. Various initiators were
      evaluated. The emulsifying and self-assembling properties were investigated by a
      water titration method. The self-assembling systems were characterized for size,
      shape, isotropic behavior, cloud point, surface charge, and critical micellar
      concentration in order to optimize the polymer synthesis. Finally, the
      improvement of solubility of model drugs was assessed. RESULTS: Only diblock
      monomethyl ether PEG-CAP/TMC copolymers synthesized with monomethyl ether
      polyethyleneglycol 550 to 2000 as initiator have shown self-assembling
      properties: upon dilution, these copolymers formed an isotropically clear
      solution with droplet sizes in the range of 20 to 100 nm. The hypothesis that
      these diblock polymers form micelles was confirmed by their low critical micellar
      concentration (10(-5) g/ml). The copolymers initated with mmePEG750 had a higher
      cloud point and better colloidal stability than those initiated with mmePEG 550.
      The solubility of the poorly water-soluble drugs was increased by 1 to 2 orders
      of magnitude. Good reproducibility was observed from batch to batch. CONCLUSIONS:
      The polyester diblock copolymer mmePEG750-CAP/TMC forms spontaneously stable
      micelles in aqueous medium and increases the solubility of lipophilic drugs. They
      are very promising vehicles for the oral delivery of poorly water-soluble drugs.

PMID- 15497684
TI  - The cohesive-adhesive balances in dry powder inhaler formulations I: Direct
      quantification by atomic force microscopy.
AB  - PURPOSE: To obtain a quantitative assessment of the cohesive and adhesive force
      balance within dry powder inhaler formulations. METHODS: The atomic force
      microscope (AFM) colloid probe technique was used to measure the adhesive and
      cohesive force characteristics of dry powder systems containing an active
      component (budesonide, salbutamol sulphate) and alpha-lactose monohydrate. To
      minimize the variations in contact area between colloid probe and substrates,
      nanometer smooth crystal surfaces of the drugs and the excipient were prepared.
      RESULTS: The uniformity in contact area allowed accurate and reproducible force
      measurements. Cohesive-adhesive balance (CAB) graphs were developed to allow
      direct comparison of the interaction forces occurring in model carrier-based
      formulations. A salbutamol sulphate-lactose system revealed a significant
      tendency for the two materials to adhere, suggesting a propensity for the powder
      to form a homogenous blend. In contrast, the budesonide-lactose system exhibited
      strong cohesive properties suggesting that the formulation may exhibit poor blend
      homogeneity and potential for segregation upon processing and handling.
      CONCLUSIONS: The novel approach provides a fundamental insight into the cohesive
      adhesive balances in dry powder formulations and further understanding of powder
      behavior.

PMID- 15497685
TI  - Phase behavior of amorphous molecular dispersions I: Determination of the degree
      and mechanism of solid solubility.
AB  - PURPOSE: To understand the phase behavior and the degree and mechanism of the
      solid solubility in amorphous molecular dispersions by the use of thermal
      analysis. METHODS: Amorphous molecular dispersions of trehalose-dextran and
      trehalose-PVP were prepared by co-lyophilization. The mixtures were exposed to 23
      degrees C, 40 degrees C, and 50 degrees C [75% relative humidity (RH)] and 23
      degrees C (69% RH) storage conditions, respectively. Thermal analysis was
      conducted by modulated differential scanning calorimeter (MDSC). RESULTS: Upon
      exposure to moisture, two glass transition temperatures (TgS), one for phase
      separated amorphous trehalose (Tg1) and the other for polymer-trehalose mixture
      (Tg2), were observed. With time, Tg2 increased and reached to a plateau (Tg(eq)),
      whereas Tg1 disappeared. The disappearance of Tg1 was attributed to
      crystallization of the phase-separated amorphous trehalose. It was observed that
      Tg(eq) was always less than Tg of pure polymer. The lower Tg(eq) when compared to
      Tg of pure polymer may be the result of solubility of a fraction of trehalose in
      the polymers chosen. The miscible fraction of trehalose was estimated to be 12%
      and 18% wt/wt in dextran at 50 degrees C/75% RH and 23 degrees C/75% RH,
      respectively, and 10% wt/wt in PVP at 23 degrees C/69% RH. CONCLUSIONS: Mixing
      behavior of trehalose-dextran and trehalose-PVP dispersions were examined both
      experimentally and theoretically. A method determining the "extent of molecular
      miscibility," referred to as "solid solubility," was developed and
      mechanistically and thermodynamically analyzed. Solid dispersions prepared at
      trehalose concentrations below the "solid solubility limit" were physically
      stable even under accelerated stability conditions.

PMID- 15497686
TI  - Characterization of suspension-based metered dose inhaler formulations composed
      of spray-dried budesonide microcrystals dispersed in HFA-134a.
AB  - PURPOSE: To assess the physicochemical characteristics and aerosol properties of
      suspensions of lipid-coated budesonide microcrystals dispersed in HFA-134a.
      METHODS: Lipid-coated budesonide microcrystals were prepared by spray-drying an
      emulsion-based feedstock. Physicochemical characteristics of spray-dried
      particles were assessed by electron microscopy, laser diffraction, and
      differential scanning calorimetry. Purity and content were determined by reverse
      phase HPLC. Particle aggregation and suspension stability were assessed visually,
      and aerosol performance was assessed by Andersen cascade impaction and dose
      content uniformity. RESULTS: Spray-drying of micronized budesonide microcrystals
      in the presence of phospholipid-coated emulsion droplets results in the
      production of low-density lipid-coated microcrystals with low surface energy.
      These spray-dried particles form stable suspensions in HFA-134a. This translates
      into good uniformity in the metered dose across the contents of the inhaler and
      acceptable aerodynamic particle size distributions (MMAD = 3.2 to 3.4 microm).
      The formulation was observed to maintain its performance over 6 months at 40
      degrees C/75% RH and 16 months at 25 degrees C/60% RH. No effect of storage
      orientation was observed on the content of first sprays following storage (i.e.,
      no Cyr effect). The fine particle dose was found to be linear out to suspension
      concentrations of about 2% wt/vol, and FPD(4.7 microm) values approaching 400
      microg can be delivered in a single inhalation. CONCLUSIONS: Engineered particles
      comprised of lipid-coated microcrystals may provide an acceptable alternative
      formulation technology for metered dose inhalers in the new hydrofluoroalkane
      propellants.

PMID- 15497687
TI  - Effect of pH, counter ion, and phosphate concentration on the glass transition
      temperature of freeze-dried sugar-phosphate mixtures.
AB  - PURPOSE: The aim of the present work is to study the interaction of phosphate
      salts with trehalose and sucrose in freeze-dried matrices, particularly the
      effect of the salts on the glass transition temperature (Tg) of the sugars.
      METHODS: Freeze-dried trehalose and sucrose systems containing different amounts
      of sodium or potassium phosphate were analyzed by differential scanning
      calorimetry to determine the Tg and by Fourier-transform infrared spectroscopy
      (FTIR) analysis to evaluate the strength of the interaction between sugars and
      phosphate ions. RESULTS: Sucrose-phosphate mixtures show an increase in Tg up to
      40 degrees C in a broad pH range (4-9) compared to that of pure sucrose. Sucrose
      phosphate mixtures exhibit a higher Tg than pure sucrose while retaining higher
      water contents. Trehalose-phosphate mixtures (having a Tg of 135 degrees C at a
      pH of 8.8) are a better option than pure trehalose for preservation of labile
      materials. The -OH stretching of the sugars in the presence of phosphates
      decreases with increase in pH, indicating an increase in the sugar-phosphate
      interaction. CONCLUSIONS: Sugar-phosphate mixtures exhibit several interesting
      features that make them useful for lyophilization of labile molecules; Tg values
      much higher than those observed for the pure sugars can be obtained upon the
      addition of phosphate.

PMID- 15497688
TI  - Metabolism and disposition of the HIV-1 protease inhibitor lopinavir (ABT-378)
      given in combination with ritonavir in rats, dogs, and humans.
AB  - PURPOSE: The objective of this study was to examine the metabolism and
      disposition of the HIV protease inhibitor lopinavir in humans and animal models.
      METHODS: The plasma protein binding of [14C]lopinavir was examined in vitro via
      equilibrium dialysis technique. The tissue distribution of radioactivity was
      examined in rats dosed with [14C]lopinavir in combination with ritonavir. The
      metabolism and disposition of [14C]lopinavir was examined in rats, dogs, and
      humans given alone (in rats only) or in combination with ritonavir. RESULTS: The
      plasma protein binding of lopinavir was high in all species (97.4-99.7% in human
      plasma), with a concentration-dependent decrease in binding. Radioactivity was
      extensively distributed into tissues, except brain, in rats. On oral dosing to
      rats, ritonavir was found to increase the exposure of lopinavir-derived
      radioactivity 13-fold. Radioactivity was primarily cleared via the hepato-biliary
      route in all species (>82% of radioactive dose excreted via fecal route), with
      urinary route of elimination being significant only in humans (10.4% of
      radioactive dose). Oxidative metabolites were the predominant components of
      excreted radioactivity. The predominant site of metabolism was found to be the
      carbon-4 of the cyclic urea moiety, with subsequent secondary metabolism
      occurring on the diphenyl core moiety. In all the three species examined, the
      primary component of plasma radioactivity was unchanged lopinavir (>88%) with
      small amounts of oxidative metabolites. CONCLUSIONS: Lopinavir was subject to
      extensive metabolism in vivo. Co-administered ritonavir markedly enhanced the
      pharmacokinetics of lopinavir-derived radioactivity in rats, probably due to
      inhibition of presystemic and systemic metabolism, leading to an increased
      exposure to this potent HIV protease inhibitor.

PMID- 15497689
TI  - Tamoxifen alters hepatic cytochrome P450 enzyme expression and circulating growth
      hormone levels in intact male rats.
AB  - PURPOSE: To investigate the effects of acute tamoxifen treatment on hepatic
      cytochrome P450 (CYP) expression and circulating thyroid and growth hormone (GH)
      levels in intact adult male rats. METHODS: Rats were injected subcutaneously with
      peanut oil (vehicle) or tamoxifen at a dosage of 20 or 200 mg/kg for 2
      consecutive days. Blood for GH measurements was collected on day 34. Rats were
      sacrificed at 37 days after treatment, trunk blood was collected, and hepatic
      microsomes were prepared. RESULTS: Mean body weight of rats treated with
      tamoxifen at 200 mg/kg was decreased compared to vehicle-treated rats throughout
      the 5-week period after treatment. Hepatic CYP2A1-dependent testosterone 7alpha
      hydroxylase activity and CYP2A1 protein content were increased, whereas CYP2C11
      mediated testosterone 2alpha- and 16alpha-hydroxylase activities and CYP2C11
      protein content were decreased significantly following tamoxifen administration.
      Peak plasma GH levels were 60% lower and nadir plasma GH levels were 30% higher
      in tamoxifen-treated relative to vehicle-treated rats. In contrast, serum
      triiodothyronine and thyroxine levels were not affected by tamoxifen treatment.
      CONCLUSIONS: Hepatic CYP enzyme expression was altered and body weight was
      decreased in adult male rats 5 weeks after treatment with tamoxifen. This
      alteration corresponded to changes in plasma GH levels.

PMID- 15497690
TI  - Assessment of the potential skin irritation of lysine-derivative anionic
      surfactants using mouse fibroblasts and human keratinocytes as an alternative to
      animal testing.
AB  - PURPOSE: The aim of this study was to identify new surfactants with low skin
      irritant properties for use in pharmaceutical and cosmetic formulations,
      employing cell culture as an alternative method to in vivo testing. In addition,
      we sought to establish whether potential cytotoxic properties were related to the
      size of the counterions bound to the surfactants. METHODS: Cytotoxicity was
      assessed in the mouse fibroblast cell line 3T6 and the human keratinocyte cell
      line NCTC 2544 using the MTT assay and uptake of the vital dye neutral red 24 h
      after dosing (NRU). RESULTS: Lysine-derivative surfactants showed higher IC50s
      than did commercial anionic irritant compounds such as sodium dodecyl sulfate,
      proving to be no more harmful than amphoteric betaines. The aggressiveness of the
      surfactants depended on the size of their constituent counterions: surfactants
      associated with lighter counterions showed a proportionally higher aggressivity
      than those with heavier ones. CONCLUSIONS: Synthetic lysine-derivative anionic
      surfactants are less irritant than commercial surfactants such as sodium dodecyl
      sulfate and hexadecyltrimethylammonium bromide and are similar to betaines. These
      surfactants may offer promising applications in pharmaceutical and cosmetic
      preparations, representing a potential alternative to commercial anionic
      surfactants as a result of their low irritancy potential.

PMID- 15497691
TI  - Isothermal titration calorimetric study of RNase-A kinetics (cCMP --> 3'-CMP)
      involving end-product inhibition.
AB  - PURPOSE: Isothermal titration calorimetry (ITC) and progress curve analysis was
      used to measure the enzyme kinetic parameters (KM and kcat) of the hydrolysis of
      cCMP by RNase-A, a reaction that includes end-product competitive inhibition by
      3'-CMP. METHODS: The heat generated from injection of 9-15 microl cCMP (20 mM)
      into bovine pancreatic RNase-A (600 nM) in 50 mM Na+ acetate buffer (pH 5.5; 37
      degrees C) was monitored for 1500-2000 s. Thermal power (dQ/dt), equal to
      (1)/deltaH(app) x d(cCMP)/dt was recorded every 1 s. The end-product inhibition
      constant (Kp) and enthalpy of the inhibitor binding interaction was obtained from
      the saturation data of 60 sequential injections of 3'-CMP (1.2 mM) into 0.05 mM
      RNase-A. The data of the plot of -d[cCMP]/dt against [cCMP] were fitted to
      kinetic equations incorporating Kp to yield KM and kcat. RESULTS: DeltaH(app) for
      each run was obtained by integration of the progress curve. The plot of 
      d[cCMP]/dt against [cCMP] yielded the kinetic parameters KM = 105.3 microM, 121.6
      microM, and 131.3 microM; kcat = 1.63 s(-1), 1.56 s(-1), and 1.71 s(-1). The end
      product bound with 1:1 stoichiometry and Kp = 53.2 microM. CONCLUSIONS: The
      combination of progress curve analysis and ITC allowed rapid and facile
      measurement of the kinetic parameters for catalytic conversion of cCMP to 3'-CMP
      by RNase-A, a reaction complicated by end-product inhibition.

PMID- 15497692
TI  - Tryptophan residues play an important role in the extraordinarily high affinity
      binding interaction of UCN-01 to human alpha-1-acid glycoprotein.
AB  - PURPOSE: To investigate the factors that contribute to the exceptionally high
      affinity binding of UCN-01 to human alpha1-acid glycoprotein (hAGP). METHODS:
      Interactions between UCN-01, UCN-02, and staurosporine with native and chemically
      modified hAGPs were examined using ultracentrifugation and spectroscopic
      analysis. RESULTS: The binding affinity of staurosporine, as well as UCN-02, to
      hAGP was lower than that of UCN-01 by 20- and 100-fold respectively. The
      percentage of UCN-01 that binds to hAGP was low at acidic pH but increased with
      increasing pH, reaching a maximum at pH 7.4. The binding of UCN-01 to
      desialylated hAGP was comparable to that of hAGP. No significant difference was
      found for the binding of UCN-01 to F1*S and A variants of hAGP. Chemical
      modification of the His, Lys, Trp, and Tyr residues caused a decrease in
      percentage of bound UCN-01. Trp-modified hAGP showed the largest decrease in
      binding. Tryptophanyl fluorescence quenching results indicate that Trp residues
      play a prominent role in the binding of UCN-01 to hAGP. CONCLUSIONS: A
      substituent at position C-7 of UCN-01 appeared to influence the binding
      specificity of the drug, and Trp residues in hAGP play a prominent role in the
      high affinity binding of UCN-01 to hAGP.

PMID- 15497693
TI  - Polyelectrolyte nanoparticles mediate vascular gene delivery.
AB  - PURPOSE: The purpose is to develop a non-viral gene delivery system that meets
      the requirements of colloidal stability of DNA complexes expressed in terms of no
      particle aggregation under physiologic conditions. The system should be used to
      transfect cardiovascular tissues. METHODS: We used a strategy based on the
      formation of polyelectrolyte nanoparticles by deposition of alternatively charged
      polyelectrolytes onto a DNA core. Polyelectrolytes were transfer RNA as well as
      the synthetic polyanion, polyvinyl sulfate (PVS), and the polycation
      polyethylenimine (PEI). The PEI/DNA complex formed the DNA core. RESULTS: We
      observed that the DNA is condensed by polycations and further packaged by
      association with a polyanion. These nanoparticles exhibited negative surface
      charge and low aggregation tendency. In vivo rat carotid artery experiments
      revealed high transfection efficiency, not only with the reporter gene but also
      with the gene encoding human urokinase plasminogen activator (Hu-uPA). Hu-uPA is
      one of the proteins involved in the recovery of the blood vessels after balloon
      catheter injury and therefore clinically relevant. CONCLUSIONS: A strategy for in
      vivo gene transfer is proposed that uses the incorporation of polyanions as RNA
      or PVS into PEI/DNA complexes in order to overcome colloidal instability and to
      generate a negative surface charge. The particles proved to be transfectionally
      active in vascular gene transfer.

PMID- 15497694
TI  - Application of novel solid lipid nanoparticle (SLN)-gene vector formulations
      based on a dimeric HIV-1 TAT-peptide in vitro and in vivo.
AB  - PURPOSE: To optimize gene delivery of SLN-based gene vectors by incorporation of
      a dimeric HIV-1 TAT peptide (TAT2) into SLN gene vectors. METHODS: Plasmid DNA
      was complexed with two SLN preparations either with or without pre-compaction of
      DNA by TAT2, poly-L-arginine, or the mutant TAT2-M1. DNA complexed with
      polyethylenimine (PEI) served as a standard. Gene expression was analyzed upon
      transfection of bronchial epithelial cells in vitro and after intratracheal
      instillation or aerosol application to the lungs of mice in vivo. Stability of
      DNA was analyzed by agarose gel electrophoresis. RESULTS: Incorporation of TAT2
      into SLN gene vectors induced an up to 100-fold sequence-dependent increase of
      gene expression as compared with the mutant TAT2-M1 and was 4- to 8-times higher
      as compared with PEI in vitro. In vivo application of TAT2-SLN gene vectors via
      jet nebulization increased SLN-based gene expression but was accompanied with DNA
      degradation. DNA degradation was not observed when an innovative device operating
      on the principle of a perforated vibrating membrane was used. CONCLUSIONS:
      Incorporation of TAT2 into SLN gene vectors is suitable to optimize gene transfer
      in vitro. The use of a mild nebulization technology avoids DNA degradation and
      offers the opportunity for further studies in large animal models.

PMID- 15497695
TI  - In vitro and in vivo metabolism of the anti-cancer agent CI-1040, a MEK
      inhibitor, in rat, monkey, and human.
AB  - PURPOSE: The use of in vitro and in vivo models using both rodent and non-rodent
      species plays an important role with regard to metabolism during the drug
      development process. In this study, we compared the metabolism of a MEK inhibitor
      (CI-1040) using in vitro and in vivo models with that observed in a cancer
      patient. METHODS: Radiolabeled CI-1040 was assessed for metabolism using rat and
      monkey liver microsomes and hepatocytes, as well as in Wistar rats and cynomolgus
      monkeys via oral administration. Human bile and plasma samples were obtained
      immediately after administration of CI-1040 to a patient with advanced colon
      cancer. A combination of HPLC-radiochromatography (HPLC-RAM), LC/MS and LC/MS/MS
      experiments were used to analyze all resulting metabolites. Unlabeled CI-1040 was
      administered (100 mg/day, QD) for 15 days to a patient suffering from colon
      cancer. Bile was collected by the insertion of a T-tube directly into the bile
      duct over a 14-h period. Metabolites were also monitored in the patient's plasma.
      RESULTS: Analysis of the metabolites in all species using in vitro and animal
      models demonstrated that CI-1040 undergoes extensive oxidative metabolism (14
      metabolites identified) with subsequent glucuronidation of the hydroxylated
      metabolites. Metabolites were predominantly excreted through the bile in the
      animal models. CONCLUSIONS: Overall, the in vitro and animal models in
      combination provided comprehensive coverage for all metabolites observed in human
      bile and plasma. In conclusion, the results obtained in this study demonstrate
      the utility of conducting investigations across species in order to gain complete
      coverage for successfully predicting human metabolites of new compounds in
      development.

PMID- 15497696
TI  - Role of PEPT2 in the choroid plexus uptake of glycylsarcosine and 5
      aminolevulinic acid: studies in wild-type and null mice.
AB  - PURPOSE: To determine the importance of PEPT2 in the uptake of glycylsarcosine
      (GlySar) and 5-aminolevulinic acid (5-ALA) in mouse choroid plexus whole tissue.
      METHODS: Uptake studies were performed in bicarbonate artificial cerebrospinal
      fluid buffer using choroid plexuses isolated from PEPT2+/+ and PEPT2-/- mice.
      [14C]GlySar and [14C]5-ALA were studied as a function of temperature,
      concentration, potential inhibitors, and low sodium conditions. RESULTS: PEPT2-/-
      mice exhibited a 90% reduction in GlySar uptake (p < 0.001) and a 92% reduction
      in 5-ALA uptake (p < 0.001) as compared to wild type animals. At 4 degrees C (vs.
      37 degrees C), GlySar uptake was reduced by 95% in PEPT2+/+ mice; no difference
      was observed in null animals. Unlabeled GlySar inhibited the uptake of
      [14C]GlySar in PEPT2+/+ mice (p < 0.01); self-inhibition did not occur in PEPT2-/
      mice. GlySar demonstrated saturable uptake in PEPT2+/+ mice (Vmax = 16.4 pmol
      mg(-1) min(-1), Km = 70 microM, Kd = 0.014 microl mg(-1) min(-1)), however,
      uptake was linear in PEPT2-/- mice (Kd = 0.023 microl mg(-1) min(-1)). Low sodium
      buffer (1 mM) resulted in 75% and 59% reductions, respectively, in GlySar (p <
      0.001) and 5-ALA (p < 0.01) uptake in PEPT2+/+ mice; no differences were observed
      in PEPT2-/- mice. Overall, about 90-95% of the choroid plexus uptake of GlySar
      and 5-ALA was mediated by PEPT2, with about 5-10% of the residual uptake
      occurring by nonspecific mechanisms. CONCLUSIONS: The results demonstrate that
      PEPT2 is the only transporter responsible for the choroid plexus uptake of GlySar
      and 5-ALA. They also suggest a role for PEPT2 in the clearance of dipeptides and
      endogenous peptidomimetics from cerebrospinal fluid.

PMID- 15497697
TI  - Interactions of human P-glycoprotein with simvastatin, simvastatin acid, and
      atorvastatin.
AB  - PURPOSE: In this study, P-glycoprotein (P-gp) mediated efflux of simvastatin
      (SV), simvastatin acid (SVA), and atorvastatin (AVA) and inhibition of P-gp by
      SV, SVA, and AVA were evaluated to assess the role of P-gp in drug interactions.
      METHODS: P-gp mediated efflux of SV, SVA, and AVA was determined by directional
      transport across monolayers of LLC-PK1 cells and LLC-PK1 cells transfected with
      human MDR1. Inhibition of P-gp was evaluated by studying the vinblastine efflux
      in Caco-2 cells and in P-gp overexpressing KBV1 cells at concentrations of SV,
      SVA, and AVA up to 50 microM. RESULTS: Directional transport studies showed
      insignificant P-gp mediated efflux of SV, and moderate P-gp transport [2.4-3.8
      and 3.0-6.4 higher Basolateral (B) to Apical (A) than A to B transport] for SVA
      and AVA, respectively. Inhibition studies did not show the same trend as the
      transport studies with SV and AVA inhibiting P-gp (IC50 -25-50 microM) but SVA
      not showing any inhibition of P-gp. CONCLUSIONS: The moderate level of P-gp
      mediated transport and low affinity of SV, SVA, and AVA for P-gp inhibition
      compared to systemic drug levels suggest that drug interactions due to
      competition for P-gp transport is unlikely to be a significant factor in adverse
      drug interactions. Moreover, the inconsistencies between P-gp inhibition studies
      and P-gp transport of SV, SVA, and AVA indicate that the inhibition studies are
      not a valid means to identify statins as Pgp substrates.

PMID- 15497698
TI  - Formulation optimization of paclitaxel carried by PEGylated emulsions based on
      artificial neural network.
AB  - PURPOSE: To develop paclitaxel carried by injectable PEGylated emulsions, an
      artificial neural network (ANN) was used to optimize the formulation--which has a
      small particle size, high entrapment efficiency, and good stability--and to
      investigate the role of each ingredient in the emulsion. METHODS: Paclitaxel
      emulsions were prepared by a modified ethanol injection method. A computer
      optimization technique based on a spherical experimental design for three-level,
      three factors [soybean oil (X1), PEG-DSPE (X2) and polysorbate 80 (X3)] were used
      to optimize the formulation. The entrapment efficiency of paclitaxel (Y1) was
      quantified by HPLC; the particle size of the emulsions (Y2) was measured by
      dynamic laser light scattering and the stability of paclitaxel emulsions was
      monitored by the changes in drug concentration (Y3) and particle size (Y4) after
      storage at 4 degrees C. RESULTS: The entrapment efficiency, particle size and
      stability of paclitaxel emulsions were influenced by PEG-DSPE, polysorbate 80,
      and soybean oil. Paclitaxel emulsions of small size (262 nm), high entrapment
      efficiency (96.7%), and good stability were obtained by the optimization.
      CONCLUSIONS: A novel formulation for paclitaxel emulsions was optimized with ANN
      and prepared. The contribution indices of each component suggested that PEG-DSPE
      mainly contributes to the entrapment efficiency and particle size of paclitaxel
      emulsions, while polysorbate 80 contributes to stability.

PMID- 15497699
TI  - An integrated model for the analysis of pharmacokinetic data from microdialysis
      experiments.
AB  - PURPOSE: To develop an integrated model for microdialysis data that incorporates
      all data including the recovery measurements in one model, and to compare this
      model to a previous model and the results from a noncompartmental analysis.
      METHODS: The models were developed in NONMEM. The modes of analysis were compared
      with respect to parameter estimates, model structures, gained mechanistic
      insight, and practical aspects. RESULTS: Both modeling approaches resulted in
      similar model structures. The parameter estimates in blood and brain from the
      models and the results from the noncompartmental analysis were comparable. Using
      the integrated model all data, that is, the total arterial concentrations, the
      venous and brain dialysate concentrations, and the recovery measurements, were
      analyzed simultaneously. CONCLUSION: The theoretical benefits of the integrated
      model are related to the inclusion of the recovery in the model and the use of
      all collected data as it was observed. Thus, all data are described in a single
      model, corrections for the recovery and the protein binding are done within the
      model, and the dialysate observations are described by the integral over each
      collection interval. Thereby, the variability and the uncertainty in the model
      parameters are handled correctly to give more reliable parameter estimates.

PMID- 15497700
TI  - Early prediction of pharmaceutical oxidation pathways by computational chemistry
      and forced degradation.
AB  - PURPOSE: To show, using a model study, how electronic structure theory can be
      applied in combination with LC/UV/MS/MS for the prediction and identification of
      oxidative degradants. METHODS: The benzyloxazole 1, was used to represent an
      active pharmaceutical ingredient for oxidative forced degradation studies. Bond
      dissociation energies (BDEs) calculated at the B3LYP/6-311+G(d,p)//B3LYP/6-31G(d)
      level with isodesmic corrections were used to predict sites of autoxidation. In
      addition, frontier molecular orbital (FMO) theory at the Hartree-Fock level was
      used to predict sites of peroxide oxidation and electron transfer. Compound 1 was
      then subjected to autoxidation and H2O2 forced degradation as well as formal
      stability conditions. Samples were analyzed by LC/UV/MS/MS and degradation
      products proposed. RESULTS: The computational BDEs and FMO analysis of 1 was
      consistent with the LC/UV/MS/MS data and allowed for structural proposals, which
      were confirmed by LC/MS/NMR. The autoxidation conditions yielded a number of
      degradants not observed under peroxide degradation while formal stability
      conditions gave both peroxide and autoxidation degradants. CONCLUSIONS:
      Electronic structure methods were successfully applied in combination with
      LC/UV/MS/MS to predict degradation pathways and assist in spectral
      identification. The degradation and excipient stability studies highlight the
      importance of including both peroxide and autoxidation conditions in forced
      degradation studies.

PMID- 15497701
TI  - Use of inverse gas chromatography (IGC) to determine the surface energy and
      surface area of powdered materials.

PMID- 15497702
TI  - [Influence of Ureaplasma urealyticum infection on the sperm-egg binding
      associated molecule, sulfogalactosylglycerolipid].
AB  - OBJECTIVE: To study the influence of Ureaplasma urealyticum (Uu) infection on the
      sperm-egg binding associated molecule, sulfogalactosylglycerolipid (SGG).
      METHODS: Epididymal sperm was collected from adult mice. The sperm suspension was
      randomly divided into 4 groups: Uu group (coincubated with Uu suspension), medium
      group (coincubated with Uu medium), normal group and PRS group. The indirect
      immunofluorescence technique was used to localize SGG on the sperm membrane and
      to observe the influence of Uu on SGG. RESULTS: In the epididymal sperm, SGG was
      localized to the head plasma membrane overlaying the acrosomal region. The SGG
      positive rate of the sperm coincubated with Uu medium was 82.0%, while that of
      the sperm coincubated with Uu suspension was reduced to 39.0% (P = 0.001).
      CONCLUSION: Uu can adhere to the sperm surface. SGG might be a membrane receptor
      on the sperm surface for Uu infection of the mammalian male genital tract. The
      blockage of SGG by Uu might be one of the molecular mechanisms correlative to
      male infertility induced by Uu infection.

PMID- 15497703
TI  - [Expression and significance of granulocyte-macrophage colony-stimulating factor
      receptors in human prostate cancer].
AB  - OBJECTIVE: To study the expression and significance of granulocyte-macrophage
      colony-stimulating factor (GM-CSF) receptors in human prostate cancer. METHODS:
      SP immunohistochemical method was employed to investigate the expression of alpha
      subunit of GM-CSF receptors in 48 cases of primary prostate cancer, 20 benign
      prostate hyperplasia samples and four kinds of cancer cell lines K562, PC-3M, HL
      60 and MCF-7. RESULTS: The total positive percentage of GM-CSF expression in
      prostate cancer was 79.2%. The positive percentages in the groups with Gleason
      score 2-4, 5-8, and 9-10 were 75%, 82.3% and 81.2% respectively. The four kinds
      of cancer cell lines had prominent GM-CSF receptor alpha subunit expression.
      CONCLUSION: It suggests that both hyperplastic and neoplastic prostate tissues
      are responsive to GM-CSF and the extensive expression of GM-CSF receptors is an
      important characteristic of prostate cancer.

PMID- 15497704
TI  - [The synergistic effects of paclitaxel and gemcitabine on prostate cancer cell
      line PC-3].
AB  - OBJECTIVE: To observe the synergistic effects of paclitaxel and gemcitabine on
      prostate cancer cell line PC-3 in vitro. METHODS: Cell morphology, MTU, flow
      cytometer and immunocytochemical method were used to observe the effects of 10(
      6), 10(-7), 10(-8) mol/L paclitaxel and 10(-7), 10(-8), 10(-9) mol/L gemcitabine
      on prostate cancer cell line PC-3 by single or synergistic administration for 48
      hours in vitro. RESULTS: Gemcitabine above 10(-8) mol/L enhanced the growth
      suppression [suppression ratio > or = (50.8 +/- 4.2)%, P < 0.05] and apoptosis
      [apoptosis ratio > or = (22.9 +/- 2.3)%, P < 0.05] and down-regulation of the
      expression of cyclin D1 [expression ratio < or = (9.6 +/- 1.6)%, P < 0.01]
      induced by paclitaxel above 10(-7) mol/L in PC-3 cells. Gemcitabine changed the
      ratio of G2/M cell arrest induced by paclitaxel from (70.3 +/- 9.7)% to (38.2 +/-
      4.2)%, and reversed the G2/M arrest partially (P < 0.01). CONCLUSION: Paclitaxel
      and gemcitabine can enhance the growth suppression and apoptosis induced by
      paclitaxel in a synergistic way. They show great potential in the treatment of
      androgen-independent carcinoma of the prostate.

PMID- 15497705
TI  - [Expression of androgen receptor and heat shock protein 90alpha in the testicular
      biopsy specimens of infertile patients with spermatogenic arrest].
AB  - OBJECTIVE: To explore the association of spermatogenic arrest with the expression
      of AR and HSP90alpha. METHODS: The two-step immunohistochemical method was used
      to examine the expression of AR and HSP90alpha in the testicular biopsy specimens
      of 57 infertile men with spermatogenic arrest, compared with those taken from 15
      normal healthy men. RESULTS: AR was expressed in the nuclei of the spermatogonia,
      spermatocytes and round spermatids of the normal testicular biopsy, but the
      intensity of the AR expression showed difference in each type of cells.
      Furthermore, the high expression of AR in spermatogonia and spermatids was on the
      margin of the cytoplasm, and perinuclear (forming a ring-like structure) were
      very distinctive in the spermatogenic arrest testicular biopsy specimens.
      HSP90alpha was expressed in spermatogonia, spermatocytes, Sertoli cells, Leydig
      cells and myoid cells in the normal testicular tissues, but highly expressed in
      the testicular tissues with spermatogenic arrest. The immunostaining intensity of
      HSP90alpha showed significant difference (P < 0.05) between the two kinds of
      testicular tissues. CONCLUSION: The results indicate that the abnormal expression
      sites of AR may make the androgen receptor unable to mediate androgen into the
      nucleus, which may down-regulate the gene transcription activity of spermatogenic
      cells. It is possible that the high expression of HSP90alpha may lead to a
      dramatic decrease in AR stability and an increase in AR abiquitirylation.

PMID- 15497706
TI  - [Effect of successive ejaculation on semen analysis parameters in normal men].
AB  - OBJECTIVE: To study the effect of successive ejaculation on semen analysis
      parameters in normal men. METHODS: Eight ejaculates were collected at daily
      intervals from 8 normal men. The semen parameters were analyzed according to WHO
      laboratory manual for the examination of human semen and sperm-cervical mucus
      interaction. RESULTS: The semen volumes and total sperm counts decreased
      gradually day by day, significantly lower from the 5th to the 8th day than the
      1st (P < 0.01). The sperm densities also declined day by day, but not
      significantly. The sperm viability and motility (a + b grade) presented an
      increasing trend, but with no significance except on the 7th day. CONCLUSION:
      With the increase of the ejaculatory frequency, human semen volumes and the total
      counts significantly decrease, while sperm viability and motility gradually
      increase. Successive ejaculation does not affect the quality of human semen.

PMID- 15497707
TI  - [Initial observation on L-carnitine for asthenospermia with epididymal knob].
AB  - OBJECTIVE: To evaluate the efficacy of L-carnitine on asthenospermia with
      epididymal knob. METHODS: Thirty-five patients aged 25-39 years with
      asthenospermia with epididymal knob were received at our clinic of andrology from
      May 2003 to July 2004, and given oral L-carnitine 2 g/d for 3 months. The sperm
      parameters of the patients were analyzed by computer-assisted sperm analysis
      system before and after L-carnitine treatment. RESULTS: Of the 32 patients who
      accomplished the 3-month L-carnitine therapy, only 4 remained unimproved in sperm
      parameters, while the other 28 were significantly improved in sperm
      concentration, forward sperm motility, total sperm motility, straight line
      velocity, curvilinear velocity and average path velocity. Four of the patients
      wives were pregnant and one patient fathered a child. CONCLUSION: Oral L
      carnitine therapy is efficacious for asthenospermia with epididymal knob.

PMID- 15497708
TI  - [Changes of semen quality in uremia patients].
AB  - OBJECTIVE: To evaluate the changes of the semen quality in uremia patients before
      renal transplantation. METHODS: The semen of 24 patients with uremia and 12
      normal volunteers was analyzed. RESULTS: The semen volume, sperm motility,
      survival rate, density and morphological normality percentage were (2.5 +/- 0.4)
      ml, (13.4 +/- 3.9)%, (25.4 +/- 5.6)%, (20.6 +/- 4.5) x 10(6)/ml and (16.8 +/-
      2.1)%, respectively, significantly lower than those of the normal group (P <
      0.01). CONCLUSION: Semen qualities were lowered significantly and spermatogenesis
      severely affected in patients with uremia.

PMID- 15497709
TI  - [Xinxibao for the treatment of chronic bacterial prostatitis].
AB  - OBJECTIVE: To study the effect of Xinxibao as a supplementary drug in the
      treatment of chronic bacterial prostatitis (CBP). METHODS: Eighty-one cases of
      CBP were divided into two groups: Group A (n = 38), treated with Xinxibao
      combined with sensitive antibiotic, and Group B (n = 43), treated with sensitive
      antibiotic only. Contrast studies were made on the therapeutic effects in the two
      groups, and the results were analyzed. RESULTS: The effectivity rate was
      significantly higher in Group A than in Group B. CONCLUSION: Xinxibao can
      effectively relieve the symptoms of CBP.

PMID- 15497710
TI  - [Clinical analysis of 7 cases of adult prostate sarcoma].
AB  - OBJECTIVE: To investigate the diagnosis, treatment and prognosis of adult
      prostatic sarcoma. METHODS: The records of 7 patients with prostate sarcoma were
      reviewed in the light of clinical manifestation, laboratory examination,
      therapeutic methods and histological subtypes. Several clinicopathological
      variables were assessed for prognostic significance. RESULTS: Of the 7 cases, 3
      were leiomyosarcoma, 3 rhabdomyosarcoma and the other malignant neurilemoma. Most
      patients presented urinary obstruction, and the diagnosis of prostate sarcoma was
      established with ultrasound guided biopsy. Histological subtypes were related to
      the rate of survival. Two patients received radical cystoprostatectomy and died
      13 and 21 months respectively after operation. Two cases underwent total pelvic
      exenteration, followed by chemotherapy and/or radiotherapy and still alive 15
      months after operation. The other 3 received only chemotherapy and/or
      radiotherapy and died 7 months on average after diagnosis. CONCLUSION: The long
      term survival rate for adults with prostate sarcoma is low. Early diagnosis and
      complete surgical resection offer patients the best chance for survival. Long
      term surveillance is necessary for the early detection of recurrence.

PMID- 15497711
TI  - [The positive effect of sildenafil on LUTS from BPH while treating ED].
AB  - OBJECTIVE: To explore the possible relationship between erectile dysfunction (ED)
      and benign prostate hyperplasia (BPH) in men, and to assess the positive effect
      of Sildenafil on the lower urinary tract symptoms (LUTS) from BPH while treating
      ED. METHODS: Thirty-two patients with ED and BPH were offered oral Sildenafil and
      reviewed before and six months after the administration of Sildenafil by the
      International Index of Erectile Function-5 (IIEF-5) and the International
      Prostate Symptom Score (IPSS) questionnaires. Scores were tested by chi-square.
      RESULTS: IIEF-5 scores were increased by 42.36% and IPSS scores declined by
      20.14%, with statistical significance (P < 0.01). CONCLUSION: Treatment of ED
      with Sildenafil appears to improve urinary symptom scores. A lower IPSS at
      baseline seems to predict a better response to Sildenafil therapy for ED.

PMID- 15497712
TI  - [Detection of free testosterone in the serum and semen of idiopathic oligospermia
      patients and its significance].
AB  - OBJECTIVE: To detect free testosterone (FT) in the serum and semen of patients
      with idiopathic oligospermia, and further analyze the relationship between FT and
      idiopathic oligospermia. METHODS: Blood samples were collected from the males of
      a normal control group (n = 44) and an idiopathic oligospermia group (n = 44) at
      8:00-10:00 a.m.. Semen samples were collected from the males of a normal control
      group (n = 30) and an idiopathic oligospermia group (n = 37) at the same time.
      Sperm density was detected by routine semen analysis, and FT in the serum and
      semen was detected by RIA. RESULTS: There was no significant difference in the
      serum concentrations of FT between the groups of normal control [(97.50 +/-
      46.96) pmol/L] and idiopathic oligospermia [(94.88 +/- 42.04) pmol/L], P > 0.5.
      But the difference was significant in the semen concentrations of FT between the
      groups of normal control [(2.01 +/- 0.32) pmol/L] and idiopathic oligospermia
      [(0.52 +/- 0.44) pmol/L], P < 0.01. CONCLUSION: Measurement of semen FT
      concentration could early reflect the function of the testis, which contributes
      to the early diagnosis and treatment of idiopathic oligospermia.

PMID- 15497713
TI  - [Tubularized incised plate urethroplasty for hypospadias (a report of 35 cases)].
AB  - OBJECTIVE: To evaluate the clinical effects of tubularized incised plate
      urethroplasty for hypospadias. METHODS: Thirty-five children aged 1 to 12 years
      with hypospadias were included in this study, 5 cases of them were glans type, 27
      cases penis type, and 3 cases penoscrotal type. Hypospadias was treated by one
      stage tubularized incised plate urethroplasty. Incised plate in the middle line
      loosened the urethral plate, and the microsurgery technique was applied during
      the suture. RESULTS: The appearance and function of the new urinary meatus was
      satisfactory. Thirty cases were successfully corrected with no urethral fistula
      and stricture. Two cases with urethral fistula and 3 cases with urinary meatus
      stricture were corrected by re-operation. Follow-up investigations were carried
      out in 32 patients. CONCLUSION: The urethral plate, close to normal urethral
      tissues, has an abundant blood supply and satisfactory elasticity. Tubularized
      incised plate urethroplasty is an ideal method for stage-one correction of
      hypospadias.

PMID- 15497714
TI  - [Relationship between the Sertoli cell and germ cell apoptosis].
AB  - Germ cells exist in an environment created by Sertoli cells. The differentiation
      of germ cells from spermatogonia to sperm in the seminiferous epithelium is
      controlled by many factors such as hormones, growth factors, temperature and
      interaction with Sertoli cells. Paracrine signaling between these intimately
      associated cells also regulates the process of germ cell death. Sertoli cells'
      products play an important role in the process of germ cell differentiation in
      the testis, in which both the spontaneous and induced germ cell apoptosis often
      occur.

PMID- 15497715
TI  - [Progress in researches on A-kinase anchor proteins in sperm].
AB  - This article reviews the advances in the studies of A-kinase anchor proteins
      (AKAPs) in sperm, including their classification, structure and mechanism. The
      influence of AKAPs that are involved on sperm mobility and acrosome reaction is
      emphasized. We hope it could play a directive role in the studies of AKAPs that
      are involved in regulating sperm mobility and acrosome reaction.

PMID- 15497716
TI  - [Efficacy and safety of vardenafil for men with erectile dysfunction].
AB  - Vardenafil is an oral, potent, highly selective phosphodiesterase 5 (PDE5)
      inhibitor. It improves erectile function significantly regardless of the etiology
      and severity of erectile dysfunction (ED) or the age of the patients. Its onset
      time leading to successful intercourse is as short as 10 minutes after
      administered orally, and in most patients it works persistently. Adverse
      reactions are generally transient and mild to moderate in nature. So vardenafil
      is both effective and safe for men with ED.

PMID- 15497717
TI  - [Pharmacodynamics and pharmacokinetics of vardenafil in patients with erectile
      dysfunction].
AB  - Vardenafil is a potent and highly selective phosphodiesterase type 5 (PDE5)
      inhibitor with a potency about 10-fold higher than sildenafil. Vardenafil can
      significantly improve erectile function and works rapidly. Vardenafil is a PDE5
      inhibitor with the fastest onset of action among its kind so far found and works
      as early as 10 minutes after oral administration, providing patients with penile
      erection sufficient to complete an intercourse. The absolute oral bioavailability
      is about 15%. Vardenafil is rapidly absorbed with a median tmax of 0.7 h and a
      terminal half-life (t1/2) of more than 4 h. The observed pharmacodynamic
      properties, pharmacokinetic characteristics and good safety and tolerability
      profile showed that vardenafil treatment provides an effective and generally well
      tolerated treatment for ED.

PMID- 15497718
TI  - Second chance for a friend.

PMID- 15497719
TI  - USS New Jersey medicine.

PMID- 15497720
TI  - A twenty-six-year-old female with hypoglycemia and hypotension.

PMID- 15497721
TI  - Taxing cosmetic surgery: another first for New Jersey.

PMID- 15497722
TI  - Multitasking can lead to miscommunication.

PMID- 15497723
TI  - Changes in premature mortality due to HIV infection in New Jersey during the
      1990s.

PMID- 15497724
TI  - The high cost of low drug prices; July-August 2004.

PMID- 15497725
TI  - Charity care is everyone's problem.

PMID- 15497726
TI  - Public health emergencies: terrorism preparedness.

PMID- 15497727
TI  - Potential hazards-with or without terrorism.

PMID- 15497728
TI  - Preparedness: response to the challenge.

PMID- 15497729
TI  - Preparedness: prevention.

PMID- 15497730
TI  - Legal issues involving bioterrorism preparedness in New Jersey. An initial
      discourse.

PMID- 15497731
TI  - New Jersey state program development for terrorism preparedness and other public
      health emergencies.

PMID- 15497732
TI  - An epidemiologist's view of bioterrorism.

PMID- 15497733
TI  - The ten most prevalent hazardous chemicals in New Jersey.

PMID- 15497734
TI  - Communicable-disease surveillance in New Jersey.
AB  - The DHSS and federal agencies have expanded their surveillance efforts to improve
      existing methods of reporting notifiable communicable diseases and to include
      additional data sources that might provide a more comprehensive view of disease
      activity in New Jersey. Currently, the DHSS is evaluating these efforts and
      recognizes several issues that need to be addressed, including: assessment of the
      timeliness, completeness, and accuracy of surveillance data; validation of
      surveillance data through comparison with hospital uniform billing data;
      characterization of the sensitivity of alerts through examination of reasons for
      identified aberrations in disease activity; evaluation of DHSS staffs and LINCS
      epidemiologists' follow-up efforts in response to alerts; evaluation of
      cumulative data trends to determine patterns in baseline disease activity (e.g.,
      variations in disease activity attributed to seasonality); development of methods
      to integrate data from all surveillance efforts to provide timely, comprehensive,
      and coordinated summaries of disease activity and to distribute these summaries
      regularly to all New Jersey public health partners to better inform public health
      and clinical management; and development of a coordinated multi-agency response
      plan in conjunction with adjacent states. Though the DHSS hopes that these
      surveillance efforts will contribute to the early detection of sentinel events
      that might represent possible bioterrorist or emerging infectious disease
      threats, the DHSS will also need to engage the medical community more fully in
      surveillance activities. In previous experiences, astute clinicians were
      responsible for the identification of the first cases of West Nile virus,
      anthrax, and SARS. Therefore, to further ensure the success of its surveillance
      efforts, the DHSS will also need to continue educating clinicians about its
      surveillance activities and the importance of timely reporting of patients with
      illness patterns that might suggest an unusual infectious disease outbreak
      associated with bioterrorism or emerging infectious diseases.

PMID- 15497735
TI  - Is New Jersey ready for a resurgence of SARS?

PMID- 15497736
TI  - New Jersey State Public Health Laboratory's bioterrorism response activities.

PMID- 15497737
TI  - Radiological terrorism.

PMID- 15497738
TI  - Nuclear power plant emergencies and thyroid cancer risk. What New Jersey
      physicians need to know.

PMID- 15497739
TI  - The bio-psycho-social consequences of terrorism.

PMID- 15497740
TI  - Education and training for public health emergencies.

PMID- 15497741
TI  - Clinical training of undergraduate communication pathology students in neonatal
      assessment and neonate-caregiver interaction in South Africa.
AB  - Developing an undergraduate clinical training module in Early Communication
      Intervention (ECI) that provides sufficient opportunity for students' learning
      experiences, and that allows contextually relevant and ethically accountable
      services to clients, as well as the dissemination of the latest scientific
      findings to both students and clients, poses a significant challenge. The article
      describes the development of a clinical training block and the development of an
      appropriate instrument for the assessment of neonatal communication skills that
      was used in this student practical. A qualitative research approach, employing a
      series of formative assessments, was used to refine the instrument. The results
      indicated changes in the content and use of the neonatal assessment instrument
      regarding the approach to infant and caregiver risk assessment; caregiver beliefs
      about neonatal capabilities; newborn state observation; caregiver training;
      language, cultural and age barriers; collaboration with nurses; kangaroo mother
      care; involvement of caregivers during the assessment; and adolescent mothers.
      The results confirmed the need for the ongoing refinement of an instrument to
      ensure quality training of students in the difficult field of neonatal
      assessments and neonate-caregiver interaction. The results also highlighted to
      the importance of initiating ECI services before birth in communities at risk for
      infant neglect and abuse, and the close relationship between ECI service delivery
      and student training.

PMID- 15497742
TI  - The performance of South African English first language child speakers on a "low
      linguistically loaded" central auditory processing test protocol.
AB  - The lack of standardized tests for central auditory processing disorders (CAPD)
      in South Africa (SA) led to the formation of a SA CAPD Taskforce, and the interim
      development of a "Low Linguistically Loaded" CAPD test protocol using test
      recordings from the 'Tonal and Speech Materials for Auditory Perceptual
      Assessment Disc 2.0'. This study compared the performance of 50 SA English first
      language child speakers (aged 8 to 12 years of age) on this protocol, with the
      previously published American normative data of Bellis (1996, 2003). Results with
      respect to predicted pass criteria as calculated by mean-2SD cutoffs, suggested
      that the SA speakers performed of a lower level than the American speakers by an
      average of 5.3% per ear for the two pair dichotic digits test, 1.9 dB for the
      masking level difference test, 8.8% per ear for the frequency pattern test-
      humming report, 14.5% per ear for the frequency patterns test--verbal report, and
      39.7% per ear for the low pass filtered speech test. Consequently, the Bellis
      (1996, 2003) data was not considered appropriate for immediate use as normative
      data in SA. Instead, the preliminary data provided in this study was recommended
      as interim normative data for SA English first language child speakers until
      larger scale SA normative data can be obtained.

PMID- 15497743
TI  - The performance of South African English first and second adult speakers on a
      "low linguistically loaded" central auditory processing test protocol.
AB  - The lack of standardized tests of central auditory processing disorder (CAPD) in
      South Africa (SA) led to the formation of a SA CAPD Taskforce, and the interim
      development of a "low linguistically loaded" CAPD test protocol using test
      recordings from the 'Tonal and Speech Materials for Auditory Perceptual
      Assessment Disc 2.0'. This study inferentially compared the performance of 16 SA
      English first, and 16 SA English second, language adult speakers on this test
      protocol, and descriptively compared their performances to previously published
      American normative data. Comparisons between the SA English first and second
      language speakers showed a poorer right ear performance (p < .05) by the second
      language speakers on the two-pair dichotic digits test only. Equivalent
      performances (p < .05) were observed on the left ear performance on the two pair
      dichotic digits test, and the frequency patterns test, the duration patterns
      test, the low-pass filtered speech test, the 45% time compressed speech test, the
      speech masking level difference test, and the consonant vowel consonant (CVC)
      binaural fusion test. Comparisons between the SA English and the American
      normative data showed many large differences (up to 37.1% with respect to
      predicted pass criteria as calculated by mean-2SD cutoffs), with the SA English
      speakers performing both better and worse depending on the test involved. As a
      result, the American normative data was not considered appropriate for immediate
      use as normative data in SA. Instead, the preliminary data provided in this study
      was recommended as interim normative data for both SA English first and second
      language adult speakers, until larger scale SA normative data can be obtained.

PMID- 15497744
TI  - Novel non-covalent azaphenylalanine thrombin inhibitors with an aminomethyl or
      amino group at the P1 position.
AB  - Design, synthesis and biological evaluation of a series of novel non-covalent
      azaphenylalanine thrombin inhibitors are presented. Replacement of the basic
      benzamidine moiety in azaphenylalanine derivatives by benzylamine (P1 part of a
      molecule) and the introduction of a N-cyclopentyl-N-methylamine moiety in the P2
      part of a molecule resulted in the thrombin inhibitor LK-733 with greatly
      increased selectivity against trypsin and an in vitro Ki of 31 nM.

PMID- 15497745
TI  - Synthesis of potential metabolites of (S)-(-)-bromofosfamide.
AB  - (S)-(-)-Bromofosfamide, a newly obtained anticancer agent, recently became a
      subject of phase I clinical trials in Poland. With the aim to study its
      metabolism in humans using phosphorus nuclear magnetic resonance a group of
      potential metabolites of this agent was synthesized.

PMID- 15497746
TI  - [Bisbenzothieno[3,2-b: 2',3'-e]pyridines].
AB  - Heating potassium 3-aminobenzo[b]thiophene-2-carboxylate (1) with ethyl
      propiolate or ethyl 3-ethoxyacrylate in acetic acid yielded the ethyl 2-(6,12
      Dihydro-bis[1]benzothieno[3,2-b:2',3'-e]pyridin-6-yl)acetate (3) as main product
      and 1,4-dihydro-[1]benzothieno[3,2-b]-4-pyridone (2) as by-product. The
      dihydropyridine (DHP) 3 was dehydrogenated with ammonium cerium nitrate (CAN) to
      give the pyridine (Py) 4. The half wave potential E(1/2) = 1.64 V showed that 3
      was much more stable against oxidizing agents than the reference compound
      nifedipine with E(1/2) = 1.15 V. Alkaline saponification of the acetic acid ester
      4 did not yield the corresponding acetic acid, because decarboxylation took place
      to form the methylpyridine 5.

PMID- 15497747
TI  - Determination of anionactive tensides using cetylpyridinium tetrachlorozincate as
      titrant. Analytical methods in respect to environmental and economical concern,
      part 20.
AB  - Sodium lauryl sulphate (sodium dodecylsulphate) can be determined in aqueous
      medium using cetylpyridinium tetrachlorozincate as standard solution and methyl
      orange resp. bromophenol blue as indicator. However, the determination of
      cetostearyl sulphate is problematic due to its slight solubility in cold water.
      Therefore, the titration has to be performed in warm solution. As well with
      methyl orange as with bromophenol blue the change of the indicator has to be
      titrated to colour shade. A photometric detection is recommended. The visual
      indication concerning the determination of the content of the technical solutions
      of the secondary paraffin sulphonates such as Ateban TH liquid and Marlon PS 30
      is also critical.

PMID- 15497748
TI  - [Bromometric assay of alprenolol and oxprenolol].
AB  - Alprenolol (1a) reacts with an excess of bromine to yield the tribromo derivative
      3a by addition and monosubstitution, while applying oxprenolol (1b) the
      disubstituted tetrabromo derivative 2b is obtained. The N-dealkylated substance
      3c was isolated as a by-product. Heating the compounds 2b and 3a with potassium
      hydroxide in acetone gives the 2-bromoallyl derivatives 5. Using potassium tert
      butanolate the 2-propyne 7 is formed from 3a. The different colours, obtained
      from 1a, 1b, pindolol and propranolol with perchloric acid in acetic acid or
      conc. sulfuric acid, are suitable for the identification test in the European
      Pharmacopoeia.

PMID- 15497749
TI  - A novel preparation of solid lipid nanoparticles with cyclosporin A for prolonged
      drug release.
AB  - Solid lipid nanoparticles were prepared by a novel solvent diffusion method in an
      aqueous system. The lipophilic model drug cyclosporin A was incorporated into SLN
      to study encapsulation efficiency, zeta potential (charge) and drug delivery.
      Stearylamine and cyclosporin A were dissolved in ethanol and acetone and the
      resultant organic solution was dropped into water at 60 degrees C. The drug
      loaded SLN suspension quickly formed with an azury color. After burst drug
      release with 18% of the drug over the first 12 hours, a distinctly prolonged
      release over a monitored period of 16 days was observed, with nearly 4% of the
      drug being released each day. These results demonstrate the suitability of SLN
      produced with the proposed method as a prolonged release formulation for
      lipophilic drugs.

PMID- 15497751
TI  - Comparative in vitro performance evaluation of the Novopulmon 200 Novolizer and
      Budesonid-ratiopharm Jethaler: two novel budesonide dry powder inhalers.
AB  - A special single dose collector and a multi stage liquid impinger were used to
      assess the consistency of delivered dose and fine particle fraction respectively,
      of the Novopulmon 200 Novolizer (Viatris, Frankfurt, Germany) and Budesonid
      ratiopharm Jethaler (Ratiopharm, Ulm, Germany). The obtained average delivered
      dose from the Jethaler at 4 kPa is 199 microg (99.5% of the label claim) versus
      219 microg (109.6%) for the Novolizer (mean of 90 doses from the same device).
      The corresponding relative standard deviation (RSD) for the Jethaler is on
      average 14.05% (maximal and minimal dose are 289 and 148 microg respectively),
      versus an RSD of 5.56% for the Novolizer (max. is 240; min. is 187 microg). It
      can be shown that the rather extreme spread in the delivered dose from the
      Jethaler is caused by a variation in metered mass, and to less extent by a poor
      content uniformity of the drug-lactose compact. The fine particle fractions
      (FPFs, as percent of label claim, for particles <5.1 microm) of both devices show
      an increase with increasing pressure drop across the inhalers, although at 4 kPa
      already 62% (Jethaler), respectively 72% (Novolizer) of the 'maximal' value (at 8
      kPa) is achieved. FPF from the Novolizer is highest at all pressure drops and
      varies between 23.2% (at 2 kPa) and 54.3% (at 8 kPa). The difference in FPF
      between both devices increases with decreasing upper class for the FPF: the ratio
      of FPF from Novolizer to that from Jethaler (at 4 kPa) is 1.42 for particles <
      5.1 microm versus 2.14 for particles < 1.8 microm, suggesting that the aerosol
      produced by the Novolizer has much greater potential for deep lung deposition.

PMID- 15497750
TI  - Hydroxypropyl methylcellulose microspheres with piroxicam and piroxicam
      hydroxypropyl-beta-cyclodextrin inclusion complex.
AB  - Inclusion complexation between piroxicam (PX) and hydroxypropyl-beta-cyclodextrin
      (HPbetaCD) in the presence of hydroxypropyl methylcellulose (HPMC) was studied in
      aqueous solution and in the solid state. Phase solubility studies were used to
      evaluate the HPbetaCD complexation in the presence of HPMC. Stability constants,
      Ks, of the complexes were determined. The stability of the inclusion complex was
      improved in the presence of HPMC. Solid microspheres were obtained by spray
      drying, and were characterized by differential scanning calorimetry (DSC),
      regarding drug content, and particle size distribution. Scanning electron
      microscopy (SEM) was also used to characterize the systems prepared. In the solid
      system HPMC facilitated to some extent the drug dissolution due to increased
      solubility. The presence of HPMC and HPbetaCD in the microspheres promoted
      dissolution rate. Cyclodextrin complexation increased PX flux through a
      semipermeable membrane. Presence of HPMC in the system additionally increased the
      drug flux more than 80%, by increasing the drug solubility and consequently the
      affinity of the ternary complex for the aqueous diffusion layer in the donor
      compartment.

PMID- 15497752
TI  - Multivariate spectral calibration technique based on regression analysis for the
      quantitative multiresolution of a ternary mixture containing paracetamol,
      ascorbic acid and acetylsalicylic acid in effervescent tablets.
AB  - Multivariate spectral calibration techniques based on regression analysis were
      established for the quantitative multiresolution of a ternary mixture containing
      parecetamol (PAR) ascorbic acid (AA) and acetylsalicylic acid (ASP) having
      closely overlapping spectra. The mathematical algorithms of multivariate spectral
      calibrations as namely tri-linear regression calibration (TLRC) and multi-linear
      regression calibration (MLRC) are based on the use of the linear regression
      equations at a three-wavelength set and a ten-wavelength set in the range of 215
      305 nm. These calibration techniques do not require any chemical pre-treatment
      and a graphical procedure of the overlapping spectra. The mathematical content of
      TLRC and MLRC approaches were briefly formulated for the quantitative analysis of
      three- or multi-component mixtures. The applicability of the formulated
      calibration models were tested by analysing the various synthetic ternary
      mixtures consisting of these active compounds and then these models were applied
      to real pharmaceutical formulations. It was observed that TLRC and MLRC models
      give a successful quantitative multiresolution. The experimental results of these
      techniques were compared with each other as well as with those obtained by
      literature methods.

PMID- 15497753
TI  - A mathematical model to predict the release of water-soluble drugs from HPMC
      matrices.
AB  - A mathematical model to predict the fraction of water-soluble drug released as a
      function of release time (t, h), HPMC concentration (CH, w/w), and volume of drug
      molecule (V, nm3) was derived with ranitidine hydrochloride, diltiazem
      hydrochloride, and ribavirin as model drugs. The model is log (M(t)/M(infinity))
      = 0.5 log t-0.3322CH-0.2222V-0.2988 (n = 140, r = 0.9848), where M(t) is the
      amount of drug released at time t, M(infinity) is the amount of drug released
      over a very long time, which corresponds in principle to the initial loading, n
      is the number of samples, and r is the correlation coefficient. The model was
      validated using isoniazid and satisfactory results were obtained. The model can
      be used to predict the release fraction of various soluble drugs from HPMC
      matrices having different polymer levels.

PMID- 15497754
TI  - Organ distribution of 5-fluorouracil loaded gelatine microspheres in mice.
AB  - The aim of this study was to investigate the organ distribution characteristics
      of 5-fluorouracil (5-Fu) loaded crosslinked gelatine microspheres (5-Fu-MS) after
      intravenous (i.v.) injection compared to 5-Fu solution in mice, and to evaluate
      the targetability of 5-Fu-MS. The concentrations of 5-Fu in mice plasma, heart,
      liver, lung, kidney, spleen and brain were determined by HPLC. The parameters
      drug targeting index C(e), time-averaged relative drug exposure values r(e), drug
      targeting efficiency t(e), and drug distributed to target-tissue (%) were used to
      evaluate the targetability of the 5-Fu-MS delivery system. The results showed
      that the concentration of 5-Fu in the lung was significantly higher than after
      application of 5-Fu solution, and that the maximum concentration of 5-Fu, 72.8
      microg x g organ(-1), was reached in the lung at 15 min after i.v.
      administration. As for 5-Fu-MS, r(e) was calculated to be 2.2, and t(e) was
      considerably higher than after application of 5-Fu in solution. Furthermore, the
      percentage of drug distributed to the lung was 2 times as high as after
      application in solution. Accordingly, 5-Fu-MS were capable of effectively
      delivering 5-Fu to the lung and possessed specific targetability towards the lung
      compared to 5-Fu solution.

PMID- 15497755
TI  - In vitro anti-inflammatory effects and immunomodulation by gemifloxacin in
      stimulated human THP-1 monocytes.
AB  - Cultured human THP-1 monocytes were exposed to serial concentrations of
      gemifloxacin over 4 h after pre-stimulation with zymogen A for 1 h or
      Staphylococcus aureus for 2 h. The following parameters were assessed: pH,
      phagocytosis, c-AMP, NO, TNFalpha, IL-1, IL-6, IL-8 and H2O2 levels, enzyme
      activities of protein kinase C, NADPH oxidase, SOD, gluthathion reductase, NAG
      and cathepsin D as well as lipid peroxidation. The reversiblity of these changes
      was determined in the presence of known blockers of the phagocytic process. The
      effects of gemifloxacin on DNA synthesis and killing of S. aureus was assessed in
      bacteria alone and in those bacteria phagocytosed by THP-1 monocytes over 24 h.
      Gemifloxacin in stimulated THP-1 monocytes over the first 30 min caused an
      increase in c-AMP, NO, H2O2 and TNFalpha levels and protein kinase C, NADPH
      oxidase, glutathione reductase, NAG and cathepsin D activities. The pH became
      more acidic and phagocytosis was stimulated. These parameters were reversed at 1
      h and continued to decline until 4 h. Lipid peroxidation was at the highest
      levels at 1 h and IL-8 levels at 2 h. DNA synthesis and bacterial growth were
      suppressed at 2 h in both S. aureus alone and bacteria phagocytosed by THP-1
      monocytes. These effects were at a higher magnitude at 24 h. Gemifloxacin
      initiates a phagocyticidal effect of THP-1 monocytes at an early time of 30 min
      which plays a role in killing bacteria but a higher magnitude of killing of
      bacteria occurs later by a standard static mechanism. This early action of
      gemifloxacin should decrease the spread of infection and the inflammatory
      response since the tissue destruction process was attenuated at 4 h.

PMID- 15497756
TI  - Spectrophotometric analysis of raloxifene hydrochloride in pure and
      pharmaceutical formulations.
AB  - Two simple and sensitive spectrophotometric methods (A and B) for the
      determination of raloxifene hydrochloride in bulk samples and pharmaceutical
      formulations are described. Method A is based on the oxidation of the drug with
      ferric chloride and coupling with potassium ferric cyanide. Method B is based on
      reduction of the drug with Fehling's reagent. Bluish green color formed in method
      A absorbs at 735 nm and brown color produced in method B absorbs at 430 nm.

PMID- 15497757
TI  - Determination of peroxide values using ethyl acetate as solvent. Analytical
      methods in respect to environmental and economical concern, part 21.
AB  - Peroxide values of fixed oils can be determined in ethyl acetate, an easily
      biodegredable solvent instead of chloroform according to PH. EUR. 2002, method A.
      Potentiometric indication is recommended. Further investigations are necessary to
      explain the high blank values obtained, when ethyl acetate is used.

PMID- 15497758
TI  - Comparison of biodegradable nanoparticles and multiple emulsions (water-in-oil-in
      water) containing influenza virus antigen on the in vivo immune response in rats.
AB  - Multiple water-in-oil-water (w/o/w) emulsion and polymeric nanoparticle
      formulations containing influenza virus surface antigen hemagglutinin (HA) are
      thought to be suitable carriers for a vaccine delivery system. The multiple
      emulsion technique leads to high entrapment of HA, while the solvent evaporation
      technique encapsulates and adsorbs HA within the nanoparticle. Immune responses
      of these formulations were investigated in rats and compared with the immune
      response raised against the conventional vaccine. The responses were detected
      with the hemagglutinin inhibition (HAI) assay. A single administration of
      multiple emulsion (F1, F2, F3) and nanoparticle (F4) formulations proved to
      stimulate a more effective immune response in rats than conventional vaccine.

PMID- 15497759
TI  - Calcium sulphate dihydrate: an useful excipient for tablets containing labile
      actives.
AB  - Tablets containing an angiotensin-converting enzyme inhibitor and either calcium
      sulphate dihydrate or lactose monohydrate as main excipients (fillers) exhibited
      similar technical properties and stability.

PMID- 15497760
TI  - Extraction of valerenic acids from valerian (Valeriana officinalis L.) rhizomes.
AB  - Extraction of valerenic acids (valerenic, acetoxyvalerenic and hydroxyvalerenic)
      from dry ground rhizomes of valerian (Valeriana officinalis L.) was studied. The
      effect of ethanol concentration in the solvent, extraction temperature and drug
      particle size on extraction kinetics were investigated and the optimum values of
      these process parameters were determined for the case of intensively stirred two
      phase dispersion. It was found that increased processing temperature favors
      extraction kinetics, but provokes moderate degradation of valerenic acids.

PMID- 15497761
TI  - Compatibility of sennoside A and B with pharmaceutical excipients.
AB  - This study reports the incompatibility of sennoside A and B with the following
      commonly used pharmaceutical excipients: stearic acid, sodium carbonate, glucose,
      lactose, propyl paraben, sodium carbonate, stearic acid, citric acid, PEG, and
      sorbitol. Drug-excipient compatibility was tested using thermal (DSC) and
      analytical (HPLC) methods of analysis. Compatibility evaluation showed that dry
      powder mixtures could be used to formulate sennoside A and B products. However,
      when mixed with water--propyl paraben, sodium carbonate, stearic acid, citric
      acid, PEG, and sugar derivatives such as lactose, glucose and sorbitol--should
      not be used in sennoside containing products.

PMID- 15497762
TI  - Phosphorohydrazines of 4-oxo-4H-1-benzopyran and 1-benzopyran-2,4-dione exhibit
      antitumor activity against L1210 leukemia.
AB  - Phosphorohydrazines and phosphorohydrazones of benzopyran-2,4-dione as well as
      the phosphorohydrazone of 4-hydroxycoumarine were tested for antitumor activity
      in lymphatic leukemia L1210 bearing mice.

PMID- 15497763
TI  - Serum cholinesterase inhibition by omeprazole and lansoprazole.
AB  - Omeprazole inhibited human and rat serum cholinesterase by approximately 5 to 60%
      over the 0.5 to 50 mg/L (1.4-140 microM) concentration range. In contrast
      lansoprazole only produced 20-30% inhibition at the highest concentration of 10
      mg/L (29 microM). Thus omeprazole but not lansoprazole is likely to potentiate
      the effect of succinylcholine at human clinical concentrations by inhibiting its
      hydrolysis in vivo by serum cholinesterases.

PMID- 15497764
TI  - Effect of water extract of Psidium guajava leaves on alloxan-induced diabetic
      rats.
AB  - A water extract of Psidium guajava leaves was screened for hypoglycemic activity
      on alloxan-induced diabetic rats. In both acute and sub-acute tests, the water
      extract, at an oral dose of 250 mg/kg, showed statistically significant
      hypoglycemic activity.

PMID- 15497765
TI  - A new homotriterpene from the roots of Marsdenia tenacissima Wight and Arn.
AB  - A new homotriterpene isolated from the roots of Marsdenia tenacissima Wight et
      Arn. has been characterized as 13-(31,32-dimethyl-30-methylene-21alpha
      acetoxytetradecanyl)-29-methyl-perhydrophenanthr-1,3-diene on the basis of
      spectral analyses.

PMID- 15497766
TI  - Polyunsaturated fatty acid regulation of gene expression.
AB  - Polyunsaturated fatty acids (PUFAs), specifically the n-3 series, have been
      implicated in the prevention of various human diseases, including obesity,
      diabetes, coronary heart disease and stroke, and inflammatory and neurologic
      diseases. PUFAs function mainly by altering membrane lipid composition, cellular
      metabolism, signal transduction, and regulation of gene expression. PUFAs
      regulate the expression of genes in various tissues, including the liver, heart,
      adipose tissue, and brain. The role of transcription factors such as SREBP1c and
      nuclear receptors such as PPAR-alpha, HNF-4alpha, and LXRalpha in mediating the
      nuclear effects of PUFAs are addressed.

PMID- 15497767
TI  - Micronutrients and the risk of type 1 diabetes: vitamin D, vitamin E, and
      nicotinamide.
AB  - Evidence from animal experiments and human observational studies suggests that
      some dietary micronutrients may protect against the development of type 1
      diabetes. The most promising data so far have been obtained for a beneficial role
      of vitamin D. Beneficial effects of vitamin E (or other antioxidants) in diabetes
      development remain hypothetical. Despite plausible theoretical background
      evidence from animal experiments and supportive data from pilot studies,
      randomized, controlled trials using nicotinamide have not provided any evidence
      for a beneficial effect.

PMID- 15497768
TI  - New roles for cysteine and transsulfuration enzymes: production of H2S, a
      neuromodulator and smooth muscle relaxant.
AB  - The enzymes of the transsulfuration pathway also have the capacity to catalyze
      the desulfhydration of cysteine. Recent studies demonstrate a role of the
      transsulfuration enzymes, cystathionine gamma-lyase and cystathionine beta
      synthase, in catalyzing the desulfhydration of cysteine in brain and smooth
      muscle. The H2S produced from cysteine functions as a neuromodulator and smooth
      muscle relaxant. In glutamatergic neurons, the production of H2S by cystathionine
      beta-synthase enhances N-methyl-D-aspartate (NMDA) receptor-mediated currents. In
      smooth muscle cells, H2S produced by cystathionine gamma-lyase enhances the
      outward flux of potassium by opening potassium channels, leading to
      hyperpolarization of membrane potential and smooth muscle relaxation.

PMID- 15497769
TI  - Hypovitaminosis D-induced pain.
AB  - Vitamin D deficiency is a problem of considerable magnitude that has reemerged as
      a major public health issue in the United States and several other developed
      countries. Vitamin D plays a crucial role in calcium homeostasis in the body.
      Hypovitaminosis D leads to osteomalacia and increased risk of fractures,
      especially in the elderly. Preliminary research suggests that vitamin D can
      prevent certain types of cancer and autoimmune diseases. A recent large study has
      shown the association between severe hypovitaminosis D and persistent, non
      specific musculoskeletal pain, further suggesting that patients with no apparent
      cause of pain should be assessed and possibly treated for vitamin D deficiency.

PMID- 15497770
TI  - A milligram of gluten a day keeps the mucosal recovery away: a case report.
AB  - In recent years it has been suggested that patients with celiac disease can be
      adequately followed up on the basis of merely clinical and serological response
      to a gluten-free diet. Thus, a duodenal biopsy some months after commencement of
      a gluten-free diet would no longer be necessary. We report here the case of a
      celiac patient in whom the ingestion of a milligram of gluten every day for 2
      years prevented histological recovery in spite of satisfactory clinical and
      serological response. The literature regarding the minimal amount of gluten that
      could be harmless to celiac patients is reviewed.

PMID- 15497771
TI  - Bone marrow pathology in AIDS.
AB  - Bone marrow morphology is frequently abnormal in patients with AIDS. In this
      study, we reviewed 97 bone marrow biopsies of AIDS patients performed between
      1998 and 2000 in the Emilio Ribas Institute of Infectology, which is the
      reference department for HIV. Specific diagnoses were performed in 33 cases.
      Fungi were observed in eight cases. Five of them were Histoplasma capsulatum, two
      were Cryptococcus neoformans, and one probably Candida albicans. Acid-fast
      bacilli were observed in 12 bone marrow biopsies, three of which were diagnosed
      to have no mycobacteriosis clinically. Foci of necrosis with clusters of
      macrophages without any well-formed granuloma were observed in nine cases and
      well-formed granuloma in three cases. Lymphomatous infiltration was observed in
      four cases of non-Hodgkin's lymphoma and in two Hodgkin's diseases (mixed
      cellularity). Extensive necrosis of bone marrow was observed in one case of
      Burkitt's lymphoma. In conclusion, bone marrow biopsy should be performed to
      elucidate the etiology of cytopenias, secondary infections, and fever of
      undetermined origin in AIDS patients.

PMID- 15497772
TI  - Quantitation of conventional histologic parameters and biologic factors in
      prostatic needle biopsy are useful to distinguish paramalignant from malignant
      disease.
AB  - The scope of this work was to determine the potential use of prostatic
      conventional histologic parameters and biologic factors in distinguishing between
      paramalignant and malignant prostatic disease, taking into account benign
      fragments of biopsies obtained from patients with prostatic cancer or from
      patients suspected to have cancer. Each prostate sample was semi-quantified for
      macronucleoli, mucin, crystalloid, collagen micronodules, and quantified for
      glands, stroma, AgNOR, and p53. The database covered 185 biopsy specimens from
      136 patients: 56 samples from the same number of patients in whom all the
      biopsies were benign; 49 samples from patients whose biopsies showed malignant
      features, and 80 malignant samples. Discriminant analysis of the results showed
      statistical differences for four parameters: macronucleoli, mucin, gland volume,
      and AgNOR, allowing us to identify three patterns of prostate involvement:
      normal, paramalignant, and malignant. The discriminant function permitted an
      adequate classification of the three patterns in 84% of the cases. Normal areas
      showed glands with a mean volume of 38.93 microm3, inconspicuous nucleoli, low
      mucin production, and a mean AgNOR area of 1.26 microm2. Prostatic biopsies with
      prominent nucleoli and the presence of mucin (60%), gland volume of 22.31
      microm3, and AgNOR area of 2.14 microm2 characterized the paramalignant
      condition. Malignant areas were characterized by mean glands with a volume of
      8.11 microm3, prominent nucleoli, high mucin secretion (100%), and AgNOR area of
      4.47 microm2. We concluded that modifications in prostate histoarquitecture and
      function, such as the presence of macronucleoli, volume of glands, abnormal
      secretion of acid mucin and AgNOR expression, represent important parameters that
      must be incorporated in the pathologist's evaluation of prostate biopsies to the
      purpose of indicating a subsequent biopsy, particulary in those patients with
      clinical suspicion of malignancy, and whose prostate biopsy specimen showed
      paramalignant areas.

PMID- 15497773
TI  - Chlamydia pneumoniae in coronary bypass grafts of redo patients. The concept of
      the 'adventitial baseline infection'.
AB  - The pathogenic role of Chlamydia pneumoniae in late coronary bypass graft failure
      has not yet been extensively investigated. We examined failed and new
      arterial/venous bypass grafts using immunohistochemistry, polymerase chain
      reaction (PCR), and serology. Thirty-four long-term failed grafts and 28 new
      grafts were examined in 21 patients undergoing redo coronary artery bypass
      grafting (CABG). Immunohistochemically, 28 (82%) failed grafts were positive in
      the intimal-medial compartment, and 33 grafts (97%) were positive for C.
      pneumoniae in the adventitia. Thirteen (46%) and 27 (96%) new grafts showed
      infection in the intima-media and in the adventitia, respectively (p < 0.05).
      Immunohistochemically, the overall presence of C. pneumoniae in all vessels
      examined was 66% in the intima-media and 97% in the adventitia (p < 0.05). C.
      pneumoniae was detected by PCR in 19 (31%) of all the vessels examined. C.
      pneumoniae seems to be frequently present in grafts of patients considered for
      redo CABG in Hungary. The adventitia of both failed, and new grafts particularly
      often contained C. pneumoniae. The results suggest that there exists an
      adventitial baseline infection from which infection of the inner wall layers
      develops, depending on local microenvironmental conditions. This is the first
      study to evaluate chlamydial infection in arterial/venous coronary grafts by
      immunohistochemistry, PCR, and serology.

PMID- 15497774
TI  - High mobility group I-C protein in astrocytoma and glioblastoma.
AB  - High mobility group I-C (HMGI-C) protein is a non-histone DNA-binding factor that
      organizes active chromatin. This protein is expressed during the limited phase of
      embryonic development and may regulate the expression of genes critical for
      embryonic cell growth and differentiation. As embryonic mechanisms are also known
      to play a role in the development of some neoplasms, we investigated human brain
      tumors for the expression of HMGI-C to determine its role in the differentiation
      of glial cell tumors. Immunohistochemical analysis revealed HMGI-C in all of the
      low-grade astrocytomas, in 2 of 3 anaplastic astrocytomas (grade 3), but in only
      one of 8 glioblastomas. The results were confirmed at the mRNA level by nested
      reverse-transcription polymerase chain reaction analyses. Loss of HMGI-C was also
      demonstrated in a case of glioblastoma transformed from the low-grade astrocytoma
      strongly expressing HMGI-C protein. These results suggest that HMGI-C may be
      involved in the differentiation of glial tumor cells, and that loss of HMGI-C
      expression may contribute to the transformation of low-grade astrocytoma into
      glioblastoma.

PMID- 15497775
TI  - Endometrial atypical (bizarre) stromal cells: a potential diagnostic pitfall in
      biopsy.
AB  - Atypical stromal cells (ASCs) may be detected in endometrial polyps and, more
      rarely, in normal endometrium. Owing to their worrisome cytological features,
      these cells may represent a potential diagnostic pitfall and are often
      misinterpreted as malignant, particularly in biopsy samples. We report on ASCs in
      proliferative phase endometrium of a woman who underwent biopsy for vaginal
      bleeding. Morphological and immunohistochemical features are discussed in detail.
      The differential diagnosis to endometrial malignant tumors containing atypical
      mesenchymal cells is provided.

PMID- 15497776
TI  - [Inflammatory bowel disease in three elderly patients; an unexpected diagnosis in
      long-standing abdominal complaints].
AB  - Three female patients, 68, 75 and 68 years of age, were treated symptomatically
      for long-standing abdominal complaints such as gastralgia, diarrhoea and loss of
      blood or mucus with the stools. In all cases there was no clear diagnosis and
      treatment did not relieve the complaints, even after surgery. Inflammatory bowel
      disease was ultimately established on the basis of histological analysis of both
      resection specimens and biopsies in combination with endoscopy. Clinical
      improvement was achieved after adequate treatment. Aspecific abdominal complaints
      in elderly patients have multiple differential diagnoses. The most important of
      these are diverticulitis, ischaemia and colon carcinoma. In contrast,
      inflammatory bowel disease (both Crohn's disease and ulcerative colitis) is
      usually diagnosed at a younger age. Ignoring inflammatory bowel disease as a
      cause of abdominal complaints in elderly patients could be responsible for
      inadequate treatment, higher morbidity and an increase of symptoms.

PMID- 15497777
TI  - [Forty years of discussion about perinatal mortality in the Netherlands].
AB  - In the recently published Peristat study, in which perinatal mortality in the
      countries of the European Union is compared, the figures for The Netherlands are
      higher than in the other countries. These figures are based partly on civil
      registration data. In the countries where these civil registration data were
      compared with clinical records, i.e. The Netherlands, Northern Ireland and
      Greece, a considerable underregistration was demonstrated. In The Netherlands,
      prenatal screening for congenital anomalies is less prevalent than in some other
      European countries and paediatricians are more reluctant to resuscitate seriously
      immature infants. This may have some influence on perinatal mortality figures,
      but a more fundamental question is: are the figures from various countries, based
      on national civil registration and a large number of divergent clinical
      registration systems, comparable? This question has not been answered
      satisfactorily.

PMID- 15497778
TI  - [High perinatal mortality in the Netherlands compared to the rest of Europe].
AB  - In the Peristat-project, a European collaborative study, a set of indicators has
      been defined for monitoring perinatal health outcomes. For a group of 10 core
      indicators, with variables for subgroup analysis, national registry data from 15
      European member states were collected and compared. The Netherlands was found to
      have the highest perinatal mortality in Europe: the foetal and neonatal mortality
      amounted to 7.4 and 3.5 per 1000 births, respectively. European countries differ
      in registration practices. Some countries do not register perinatal deaths
      occurring before a duration of amenorrhoea of 28 weeks. Therefore, the Peristat
      mortality data should be compared with 28 weeks of gestation as a cut-off point.
      With this cut-off point, The Netherlands has the second highest perinatal
      mortality. A number of factors may have contributed to this relatively high
      mortality, such as differences in registration practices, the profile of the
      Dutch childbearing population and the characteristics of Dutch perinatal care.
      The Netherlands has a relatively high proportion of older mothers, multiple
      births and mothers belonging to an ethnic minority. Also, Dutch neonatologists
      are known to be conservative in their treatment of premature newborns, which
      reduces their chances of survival. There is also less prenatal screening for
      congenital abnormalities in The Netherlands than in many other European
      countries. Further analysis of the Dutch data, as well as continued monitoring at
      the European level, can serve as a basis for future policy decisions to enhance
      the health of Dutch mothers and newborns.

PMID- 15497779
TI  - [Immunophenotyping of haematologic malignancies].
AB  - Over the last 10 years, immunophenotyping of haematologic malignancies has become
      an indispensable diagnostic supplement to the classical morphological approach.
      Immunophenotyping of haematopoietic cells is performed with the use of a number
      of monoclonal antibodies (MOABs), which are directed specifically against
      structures of blood cells that become expressed at the different stages of
      differentiation and maturation. Cells to which the fluorescently labelled MOABs
      are directed can be recognised and measured using fluorescence microscopy or
      fluorescence flow cytometry. Many MOABs, fluorochromes and user-friendly flow
      cytometers have become available in the last 15 years, as a result of which
      immunophenotyping is now routinely applied in clinical practice.
      Immunophenotyping has the potential to classify leukaemias and other malignant
      lymphomas according to cell type and stage of maturation. This information is
      important for the establishment of the right diagnosis and prognosis, and for the
      optimal treatment choice. In a number of cases immunophenotyping provides
      information which cannot be obtained by simple morphological investigation. The
      immunophenotyping of blood and bone-marrow cells is also a sensitive method for
      detecting minimal residual disease after an apparent complete remission has been
      achieved.

PMID- 15497780
TI  - [A national prospective trial register for randomised controlled trials: ethical
      and practical necessity].
AB  - The decision to treat a patient is often based on the results of randomised
      controlled trials (RCTs). These important investigations inform physicians and
      patients with regard to the chance of favourable results of treatment and the
      risks of adverse reactions. However, research has shown that especially the
      smaller RCTs in which no or even an adverse effect of new interventions is found
      run a relatively high risk of remaining unpublished, which leads to publication
      bias and an overestimate of the efficacy of an intervention. This is undesirable.
      The best way to identify possible publication bias and reduce its negative
      effects is to register RCTs from their starting date onwards in a prospective and
      publicly accessible register. Other motives for such a register are the
      prevention of duplication of research work and its financial support, and
      informing patients. Currently, a prospective Dutch national trial register is
      being developed by the Dutch Cochrane Centre. This is not only of importance to
      researchers and patients, but also to grant-providing bodies and the editors of
      medical scientific journals.

PMID- 15497781
TI  - [Registration of clinical trials: a statement from the International Committee of
      Medical Journal Editors].
AB  - Altruistic motives and trust are central to scientific investigations involving
      people. These prompt volunteers to participate in clinical trials. However,
      publication bias and other causes of the failure to report trial results may lead
      to an overly positive view of medical interventions in the published evidence
      available. Registration of randomised controlled trials right from the start is
      therefore warranted. The International Committee of Medical Journal Editors has
      issued a statement to the effect that the 11 journals represented in the
      Committee will not consider publication of the results of trials that have not
      been registered in a publicly accessible register such as www.clinicaltrials.gov.
      Patients who voluntarily participate in clinical trials need to know that their
      contribution to better human healthcare is available for decision making in
      clinical practice.

PMID- 15497782
TI  - [Diagnostic image (207). A woman with orange hands].
AB  - A 45-year-old woman was diagnosed with carotenaemia due to excessive intake of
      beta-carotene in a vitamin drink.

PMID- 15497783
TI  - [The determinants of the high Dutch perinatal mortality in a complete regional
      cohort, 1990-1994].
AB  - OBJECTIVE: Analysis of the effects of population-based determinants (maternal
      age, parity, multiple pregnancy and ethnicity) and of professional and
      organisational factors (conservative management in case of early preterm birth,
      the policy on prenatal screening and the Dutch obstetric-care system in general)
      on perinatal mortality. DESIGN: Population-based prospective cohort study.
      METHOD: In a regional cohort (Zaanstreek) of 8031 pregnancies in the period 1990
      1994 data were prospectively collected in an electronic database by deliverers of
      primary and secondary care. Analysis focussed on the effect on perinatal
      mortality of maternal age, parity, multiple pregnancy, ethnicity and professional
      and organisational factors (the policy in case of early preterm birth, the policy
      on prenatal screening and the Dutch obstetric-care system in general). Perinatal
      mortality was defined as mortality from a gestational age of 22 weeks until 28
      days post partum. RESULTS: The perinatal mortality in the Zaanstreek was
      12.6/1000. Increasing the gestational age to 28 weeks decreased the perinatal
      mortality by 29%. The perinatal mortality in this cohort was significantly
      affected by parity, multiple pregnancy and maternal age (relative risk: 2.8), but
      not by ethnicity if corrected for the previous factors. Conservative management
      in case of early preterm birth and a restrictive screening policy for lethal
      birth defects were associated with an increase in perinatal mortality. In 31 of
      92 singleton pregnancies followed by perinatal mortality, a relationship to
      substandard care was established. In 7 cases this relationship was probable and
      in 1 case the midwife was responsible. CONCLUSION: Given the magnitude of their
      effects, both independently and via interaction, stratification for maternal age,
      parity, multiple pregnancy and ethnicity must precede any interpretation and
      comparison of perinatal mortality rates. Although clinical policy played a modest
      role, a negative role of the organisation of obstetric care was unlikely in this
      cohort. A definitive judgement as to the quality of perinatal care would require
      extension of the evaluation to at least the entire first year of life in
      connection with the morbidity. The most favourable effects can be expected from
      stimulatory measures directed at lowering the age at first pregnancy.

PMID- 15497784
TI  - [Treatment of patients with acute coronary syndromes in the Netherlands in 2000
      2001; a comparison with other European countries and with the guidelines].
AB  - OBJECTIVE: To determine whether the guidelines for the management of acute
      coronary syndrome (ACS) are being applied in daily clinical practice, and in what
      ways the management differs between the Netherlands and other member countries of
      the European Society of Cardiology (ESC). DESIGN: Prospective, observational
      study. METHOD: Patients with a confirmed diagnosis of ACS who were enrolled in 6
      Dutch hospitals and in 97 hospitals in 24 other ESC member countries in the
      period from 4 September 2000 to 15 May 2001 were included. Data were collected on
      the acute treatment and secondary prevention in patients with ST-elevation and on
      the pharmacotherapy, risk stratification and secondary prevention in patients
      without ST-elevation. The findings were compared with the recommendations and
      guidelines of the ESC. RESULTS: A total of 223 patients with ST-elevation and 198
      patients without ST-elevation were enrolled in the Netherlands, plus 4208 and
      5169 patients, respectively, in the other European countries. The median age was
      64-67 years and the percentage of males was 64-73. Of the patients with ST
      elevation who arrived in the hospital within 12 hours after the onset of
      symptoms, 35% received neither thrombolysis nor primary percutaneus coronary
      intervention. In both the Netherlands and the rest of Europe, half of the ST
      elevation patients received thrombolysis later than 40 minutes and primary
      percutaneous coronary intervention later than 90 minutes after arrival in the
      hospital. Risk stratification using troponin measurements was applied more often
      in the Netherlands. Of the high-risk patients without ST-elevation, over 50% in
      both the Netherlands and the rest of Europe underwent coronary angiography.
      Almost 70% and 80% of low-risk, non-ST-elevation patients underwent an exercise
      tolerance test or coronary angiography. In the Netherlands, clopidogrel,
      glycoprotein IIb/IIIa antagonists and statins were prescribed more often and ACE
      inhibitors less often. CONCLUSION: Guidelines for the management of ACS were
      followed to a moderate extent in both the Netherlands and the rest of Europe. The
      management differed in a number of ways between the Netherlands and the other
      countries.

PMID- 15497785
TI  - [Eosinophilia caused by solid malignancy].
AB  - A 48-year-old woman with exanthema, pruritus and eosinophilia was found upon
      further examination to have a small-cell bronchus carcinoma; after chemotherapy
      and radiotherapy there was an almost complete response and the skin symptoms
      disappeared. A 70-year-old man who was recently treated due to primary malignant
      fibrous histiocytoma associated with eosinophilia became cachectic and anaemic.
      He was found to have a metastased leiomyosarcoma and died shortly afterwards.
      Worldwide the most common cause of eosinophilia is a parasitic infection, whereas
      in Western Europe the most common causes are allergic reactions and medicine use.
      Paraneoplastic symptoms are present in 7-10% of adults with cancer. However, the
      frequency of eosinophilia as a paraneoplastic phenomenon is unknown. It is
      important to recognise this phenomenon of paraneoplastic eosinophilia for the
      timely diagnosis and treatment of the underlying disease.

PMID- 15497786
TI  - [Severe adverse reactions after the use of sulphur hexafluoride (SonoVue) as an
      ultrasonographic contrast agent].
AB  - European Medicines Agency (EMEA) recently took precautionary measures to limit
      the use of the ultrasonographic contrast agent sulphur hexafluoride (SonoVue) in
      patients with cardiac disease. Throughout Europe a number of serious allergic
      reactions with probable secondary cardiovascular problems have been reported. In
      addition to this, there have been 3 reports of a fatal outcome soon after the
      administration of SonoVue. For all of these patients there was a risk of serious
      cardiac complications as a consequence of underlying cardiac problems. In The
      Netherlands 3 anaphylactic reactions have been reported, two in women aged 59 and
      70 years respectively, and one in a man aged 80 years.

PMID- 15497787
TI  - [The hot summer of 2003: heat stroke in Maastricht].

PMID- 15497788
TI  - [A patient with lessened sensitivity to acenocoumarol during a period of enteral
      feeding].

PMID- 15497789
TI  - [Widely divergent clinical phenotype of X-linked agammaglobulinemia in two
      cousins].

PMID- 15497790
TI  - [Do we really have to forbid therapeutic cloning?].

PMID- 15497791
TI  - [Therapeutic use of stem cells].
AB  - Stem cells display important capacities of self renewing, proliferation and
      differentiation. Because those present in the embryo have the more remarkable
      properties, their potential use in the therapy of until now incurable
      degenerative diseases have been envisioned. Embryonic stem (ES) cells are located
      in the inner mass of the balstocyst at early stages of the development. Even in
      long-term cultures they still retain their undifferentiated features. Under
      specific culture conditions, ES cells can be committed into a variety of
      differentiation pathways, giving rise to large amounts of cells corresponding to
      different tissues (neurones, cardiomyocytes, skeletal muscle, etc.). However,
      producing these tissues from already established ES cell lines would lead to
      immune rejection when transplanted to patients. To prevent this pitfall and using
      the expertise accumulated by animal cloning by nucleus transfer, it has been
      proposed to adapt this technique to human ES cells. The therapeutic cloning
      consists in transferring the nucleus of somatic stem cells isolated from the
      patient into an enucleated oocyte, to allow blastocyst development from which ES
      cells will be derived. From these stem cells, compatible tissues will be then
      produced. The problem is that it is in theoretically possible to reimplant the
      cloned blastocyst into a surrogate mother for obtaining a baby genetically
      identical to the donor. This is called reproductive cloning. This worrying risk
      raises important ethic and legal questions.

PMID- 15497792
TI  - [Chronic obstructive pulmonary disease. The heavy burden of tobacco addiction].

PMID- 15497793
TI  - [Epidemiology of chronic obstructive pulmonary disease].
AB  - Prevalence of COPD is 4 to 10% in developed countries according to spirometric
      studies. COPD is markedly under-diagnosed, only 1/3 of patients being recognised.
      COPD is the only disease whose rank among causes of death increases, placing it
      at the third place in 2020. In France, COPD-related annual mortality rate is 25
      per 100 000, which corresponds to 15 000 deaths. Between 1990 and 2020, it will
      rise from the 12th to the 5th rank among causes of handicap in the world. The
      main risk factor is tobacco smoking. Other factors with proven responsibility in
      the occurrence of COPD include some occupational exposures and inherited alpha 1
      antitrypsine deficiency. Other genetic factors, prematurity, bronchial hyper
      responsiveness and respiratory infections may also be involved.

PMID- 15497794
TI  - [COPD: from early symptoms to chronic respiratory failure].
AB  - COPD is a frequent and progressive disease, which can lead to severe respiratory
      impairment. Smoking is the main causal factor. Therefore, respiratory symptoms
      should not be underestimated in smokers. Chronic cough, chronic sputum,
      persistent dyspnea on exercise (even for sustained efforts) need further
      investigations. Each smoker has to be considered as potentially having COPD. Lung
      function measurements are required in these patients.

PMID- 15497795
TI  - [Emphysema].
AB  - The term emphysema refers both to abnormal enlargement and destruction of distal
      spaces of the lung. Diagnosis of emphysema is achieved by high resolution CT-scan
      of the thorax. Advanced forms of emphysema are associated with severe respiratory
      insufficiency. Isolated forms of emphysema may present as giant bullae with
      normal surrounding parenchyma. Diffuse panlobular emphysema is frequently
      associated with a genetic disease characterized by a severe deficit in alpha1
      antitrypsin (AAT). Common forms of emphysema are observed in the distal lung of
      patients with COPD, or around fibrous and retractile lesions of the lung. Apart
      from the possible beneficial effect of augmentation therapy in case of severe
      deficit in AAT, there is no medical therapy currently active on the emphysematous
      process. Surgical approaches include bullaectomy which may be indicated in some
      cases of giant bullae, and lung transplantation and lung volume reduction surgery
      whose indications are both restricted to selected cases of advanced emphysema.

PMID- 15497796
TI  - [Management of stable COPD].
AB  - The term chronic obstructive pulmonary disease (COPD) is mainly characterised by
      an irreversible obstructive airway obstruction, that in most cases, is secondary
      to tobacco exposure. Management of the disease includes an assessment of
      severity, and measures to decrease FEV decline, to treat bronchial obstruction,
      to improve exercise tolerance and to correct abnormal gas exchange. Treatment not
      only requires drug therapy, but also respiratory rehabilitation, surgery of
      emphysema, and psychosocial support. In this way, a global strategy, adapted to
      the severity of COPD, can be proposed.

PMID- 15497797
TI  - [Pulmonary rehabilitation in patients with chronic obstructive pulmonary
      disease].
AB  - Management of COPD has underscored the systemic dimension of the disease, but
      pulmonary rehabilitation is now recognised as a cornerstone of the treatment of
      COPD. A multidisciplinary team is needed where the general practitioner has a
      central role as a coordinator. The efficacy of pulmonary rehabilitation in
      decreasing dyspnea, improving endurance capacity, quality of life, reducing
      health related costs, is evidenced based with the highest degree of validation.
      Modalities regarding the setting: (in-based, out-based, or at home) are not
      precisely delineated but results are comparable. Finally, resources dedicated to
      pulmonary rehabilitation are inadequate regarding the growing demand.

PMID- 15497798
TI  - [Diagnosis and management of exacerbations and acute respiratory failure in
      patients with chronic obstructive pulmonary disease].
AB  - Acute episode of chronic obstructive pulmonary disease occurs in almost all
      patients, during which cough, expectoration and dyspnea increase. When the
      underlying disease is not severe and the acute episode not life-threatening, the
      term "exacerbation" is appropriate, and the patients can be managed at home. When
      the underlying disease is advanced and the acute episode possibly life
      threatening, the terms of "acute respiratory failure" or "decompensation" can be
      used. These patients are most often admitted to the hospital, and at times to the
      intensive care unit. Bronchodilators and respiratory physiotherapy form the basis
      of the management of acute episodes of COPD. In severe cases, oxygen must be
      administered, and the decision of an hospitalisation considered. Antibiotics and
      corticosteroids shoud not be prescribed in a systematic manner. In the most
      severe cases, non-invasive ventilation must be accessible. The prevention of
      acute episodes of COPD is best achieved through tobacco cessation and influenza
      vaccine. Finally, an acute episode may be an opportunity to make a diagnosis of
      COPD if this has not been done before.

PMID- 15497799
TI  - [Means and organisation of the management of severe forms of COPD].
AB  - Chronic obstructive pulmonary disease is becoming the 3rd aetiology of death by
      disease. In its advanced presentation, it generates a chronic respiratory failure
      with hypoxia and frequent hypercapnia. Its complex management implies at that
      stage a medical treatment, physiotherapy and pulmonary rehabilitation, associated
      with long-term oxygentherapy. In the most severe stages, may be discussed long
      term home mechanical ventilation with non invasive connection in order to avoid
      tracheotomy and to prevent acute respiratory episodes leading these patients in
      intensive care units and yet responsible for 15 000 deaths per year in our
      country.

PMID- 15497801
TI  - [Patient facts. What is COPD?].

PMID- 15497800
TI  - [Health status in patients with chronic obstructive pulmonary disease].
AB  - Health status is usually impaired in patients with moderate to severe chronic
      obstructive pulmonary disease. Generic and specific questionnaires have been used
      as measures of the health status. They can provide information on the patient's
      status that cannot be established using physiological evaluations. Health status
      is improved by smoking cessation, bronchodilators and rehabilitation. Inhaled
      corticosteroids can be useful in patients with more severe disease or more
      frequent exacerbations. No progress in health status has been observed with oral
      corticosteroids nor mucomodifiers. For patients with severe chronic respiratory
      failure, health status can sometimes be improved with long-term oxygenotherapy
      and supplemental oxygenotherapy during exercise.

PMID- 15497802
TI  - [A new heading].

PMID- 15497803
TI  - [National class examination].

PMID- 15497804
TI  - [Cardio-respiratory arrest].

PMID- 15497805
TI  - [Professional environment and health. Occupational medicine organization].

PMID- 15497806
TI  - [Naso-sinusoidal infections of the adult].

PMID- 15497807
TI  - [Goiter and thyroid nodules].

PMID- 15497808
TI  - [Childhood cancer. Epidemiologic, diagnostic, and therapeutic aspects].

PMID- 15497809
TI  - [Righteous doctors among the nations].

PMID- 15497810
TI  - Optimal reconstruction of historical water supply to a distribution system: A.
      Methodology.
AB  - The New Jersey Department of Health and Senior Services (NJDHSS), with support
      from the Agency for Toxic Substances and Disease Registry (ATSDR) conducted an
      epidemiological study of childhood leukaemia and nervous system cancers that
      occurred in the period 1979 through 1996 in Dover Township, Ocean County, New
      Jersey. The epidemiological study explored a wide variety of possible risk
      factors, including environmental exposures. ATSDR and NJDHSS determined that
      completed human exposure pathways to groundwater contaminants occurred in the
      past through private and community water supplies (i.e. the water distribution
      system serving the area). To investigate this exposure, a model of the water
      distribution system was developed and calibrated through an extensive field
      investigation. The components of this water distribution system, such as number
      of pipes, number of tanks, and number of supply wells in the network, changed
      significantly over a 35-year period (1962--1996), the time frame established for
      the epidemiological study. Data on the historical management of this system was
      limited. Thus, it was necessary to investigate alternative ways to reconstruct
      the operation of the system and test the sensitivity of the system to various
      alternative operations. Manual reconstruction of the historical water supply to
      the system in order to provide this sensitivity analysis was time-consuming and
      labour intensive, given the complexity of the system and the time constraints
      imposed on the study. To address these issues, the problem was formulated as an
      optimization problem, where it was assumed that the water distribution system was
      operated in an optimum manner at all times to satisfy the constraints in the
      system. The solution to the optimization problem provided the historical water
      supply strategy in a consistent manner for each month of the study period. The
      non-uniqueness of the selected historical water supply strategy was addressed by
      the formulation of a second model, which was based on the first solution.
      Numerous other sensitivity analyses were also conducted using these two models.
      Both models are solved using a two-stage progressive optimality algorithm along
      with genetic algorithms (GAs) and the EPANET2 water distribution network solver.
      This process reduced the required solution time and generated a historically
      consistent water supply strategy for the water distribution system.

PMID- 15497811
TI  - Optimal reconstruction of historical water supply to a distribution system: B.
      Applications.
AB  - In a recently completed case-control epidemiological study, the New Jersey
      Department of Health and Senior Services (NJDHSS) with support from the Agency
      for Toxic Substances and Disease Registry (ATSDR) documented an association
      between prenatal exposure to a specific contaminated community water source and
      leukaemia in female children. An important and necessary step in the
      epidemiological study was the reconstruction of the historical water supply
      strategy of the water distribution system serving the Dover Township area, New
      Jersey. The sensitivity of solutions to: (1) pressure and pattern factor
      constraints, (2) allowable operational extremes of water levels in the storage
      tanks, and (3) the non-uniqueness of the water supply solution are analysed in
      detail. The computational results show that the proposed approach yields
      satisfactory results for the complete set of monthly simulations and sensitivity
      analyses, providing a consistent approach for identifying the historical water
      supply strategy of the water distribution system. Sensitivity analyses indicated
      that the alternative strategy obtained from the revised objective function and
      the variation of constraints did not yield significantly different water supply
      characteristics. The overall analysis demonstrates that the progressive
      optimality genetic algorithm (POGA) developed to solve the optimization problem
      is an effective and efficient algorithm for the reconstruction of water supply
      strategies in water distribution systems.

PMID- 15497812
TI  - The prominence of health in donor policy for water supply and sanitation: a
      review.
AB  - Improved water supply, sanitation and hygiene used in combination are effective
      at achieving better health for poor people in developing countries. However,
      donor policy has been dominated by interventions in water supply, at the expense
      of achieving the potential health benefits of improved sanitation and hygiene.
      Commitments recently made by the international community require greater emphasis
      on improved sanitation and hygiene and their impacts on health. This review
      assesses whether such a shift in emphasis is apparent in donor policy. It
      examines the prominence given to achieving better health in water supply and
      sanitation policies of three donors: the World Bank, the European Union and the
      Department for International Development of the British Government. It finds that
      health benefits are explicit and integral in recently updated policy
      documentation concerning water supply and sanitation. This has taken place in an
      environment focused on poverty reduction and demand-led, financially sustainable
      interventions. Mechanisms that have enabled donors to prioritise the health
      impacts in this environment are discussed, including adoption of an asset-based
      conceptualisation of poverty and a cross-sectoral approach.

PMID- 15497813
TI  - Usefulness of monitoring tropical streams for male-specific RNA coliphages.
AB  - The objective of this study was to evaluate the usefulness of monitoring streams
      in Hawaii for FRNA coliphages as a reliable indicator of sewage contamination.
      This study was undertaken as a result of our previous findings that monitoring
      streams in Hawaii for traditional faecal indicator bacteria (faecal coliform,
      Escherichia coli, enterococci) was not useful in determining when streams are
      contaminated with sewage, because environmental (soil) sources rather than sewage
      accounted for the high concentrations of faecal bacteria in streams. Two
      perennial streams, sewage and soil samples were monitored for traditional faecal
      indicator bacteria (faecal coliform, E. coli, enterococci) and FRNA coliphages.
      The results showed that sewage treatment processes and disinfection drastically
      reduced the concentrations of traditional faecal indicator bacteria but FRNA
      coliphages were still present in significant concentrations in the treated sewage
      effluents. These results indicate that monitoring sewage effluents and
      environmental waters for only traditional faecal indicator bacteria may not be
      adequately protective of human health effects. Ambient concentrations of
      traditional faecal indicator bacteria in soil and streams of Hawaii were
      consistently high but consistently low for FRNA coliphages, indicating that
      monitoring streams of Hawaii for FRNA coliphages can be used to determine when
      streams are contaminated with sewage.

PMID- 15497814
TI  - Waterfowl and the bacteriological quality of amenity ponds.
AB  - This study investigated the impact of waterfowl on the bacteriological quality of
      village ponds in East Yorkshire, north-east England. Water and sediment samples
      were collected from ponds with and without resident ducks and geese; faecal
      indicator and potentially pathogenic bacteria were assayed by membrane filtration
      and by selective enrichment. Escherichia coli, faecal streptococci and, to a
      degree, Clostridium perfringens were more abundant in ponds with waterfowl;
      Salmonella was isolated in June-August from the sediment of a pond with
      waterfowl. The results suggested that the bacteriological quality of village
      ponds might be adversely affected by waterfowl. All water samples from ponds with
      waterfowl had faecal indicators at higher concentrations than EU requirements for
      bathing waters. Although these ponds are not bathing waters we suggest skin
      contact and accidental ingestion of water should be avoided.

PMID- 15497815
TI  - Cryptosporidium and Giardia in swimming pools in the Netherlands.
AB  - The occurrence of Cryptosporidium and Giardia in indoor swimming pools in the
      Netherlands was studied at five locations. The backwash water from seven pool
      filters was analysed for the presence of Cryptosporidium oocysts and Giardia
      cysts for a period of 1 year. Of the 153 samples of filter backwash water
      analysed, 18 (11.8%) were found positive for either Cryptosporidium (4.6%),
      Giardia (5.9%) or both (1.3%). Oocysts and cysts were also detected in the water
      of one toddler pool and one learner pool. Although most of the (oo)cysts in the
      filter backwash water were dead, viable and potentially infectious oocysts were
      detected in the learner pool. On the basis of numbers of potentially infectious
      (oo)cysts detected in the learner pool, and assuming one visit to an infected
      pool per year, risk assessment indicated an estimated risk of infection with
      Cryptosporidium that exceeded the generally accepted risk of one infection per
      10,000 persons per year. Guidelines for pool operators on how to manage faecal
      accidents and public information on the importance of hygiene in swimming pool
      complexes are recommended tools in controlling the risk of infection.

PMID- 15497816
TI  - Assessment of drinking water quality using indicator bacteria and bacteriophages.
AB  - Bacterial indicators and bacteriophages suggested as potential indicators of
      water quality were determined by public laboratories in water from springs,
      household water wells, and rural and metropolitan water supplies in north-eastern
      Spain. Indicator bacteria were detected more frequently than bacteriophages in
      springs, household water wells and rural water supplies. In contrast, positive
      bacteriophage detections were more numerous than those of bacteria in
      metropolitan water supplies. Most of the metropolitan water supply samples
      containing indicators had concentrations of chlorine below 0.1 mg l(-1), their
      indicator loads resembling more closely those of rural water supplies than any
      other samples taken from metropolitan water supplies. The number of samples from
      metropolitan water supplies containing more than 0.1 mg l(-1) of chlorine that
      contained phages clearly outnumbered those containing indicator bacteria. Some
      association was observed between rainfall and the presence of indicators.
      Sediments from service reservoirs and water from dead ends in the distribution
      network of one of the metropolitan water supplies were also tested. Bacterial
      indicators and phages were detected in a higher percentage than in samples of tap
      water from the same network. Additionally, indicator bacteria were detected more
      frequently than bacteriophages in sediments of service reservoirs and water from
      dead end samples. We conclude that naturally occurring indicator bacteria and
      bacteriophages respond differently to chlorination and behave differently in
      drinking water distribution networks. Moreover, this study has shown that testing
      for the three groups of phages in routine laboratories is easy to implement and
      feasible without the requirement for additional material resources for the
      laboratories.

PMID- 15497817
TI  - A comparison between in vitro rat and human and in vivo rat skin absorption
      studies.
AB  - In vitro skin penetration rates in rat and man were compared to those obtained in
      vivo in rats. Saturation of absorption was frequently observed at higher exposure
      levels in in vitro and in vivo. Lipophilic compounds showed the highest
      penetration rates through rat skin in vitro. In all cases in vitro dermal
      penetration through rat skin was higher than in vivo. Thus, the in vitro study
      may serve as a first tier test. The in vivo data suggest an inverse relationship
      between molecular weight and the rate of dermal absorption for lipophilic as well
      as hydrophilic compounds. Rat skin was more permeable to all tested substances
      than human skin (mean difference 10.9-fold). Thus, the systemic exposure of
      humans may be significantly overestimated if risk assessment is based only on the
      results of an in vivo rat study, because human skin is less permeable than rat
      skin. It would appear, therefore, that an estimate of actual dermal penetration
      through human skin should be based on the combined use of in vivo and in vitro
      data, using the following equation: % Human dermal penetration = (% rat in vivo
      dermal penetration) x (in vitro rate dermal penetration human / in vitro rate
      dermal penetration rat).

PMID- 15497818
TI  - Thioacetamide differentially affects the expression and activity of glutathione-S
      transferase in the liver of Wistar rats.
AB  - Glutathione-S-transferase (GST) is a family of enzymes involved in the
      detoxification of toxic and carcinogenic compounds. In the present study, the
      effect of thioacetamide (TA), a hepatotoxic and hepatocarcinogenic compound, on
      the activity and expression of GST of Wistar female rats was tested. Animals were
      treated with a single dose of TA (250 mg/kg) for 12, 24, 48 and 72 hours. GST
      activity toward the broad substrate 1-chloro-2,4-dinitrobenzene was enhanced by
      TA. The protein level of the GST classes alpha and mu as well as the mRNA level
      of several GST subunits were also positively affected by the TA treatment. Female
      Wistar rats of the same age but from two other different colonies had their GST
      activity either inhibited or not affected by TA. The basal mRNA level of class
      alpha and class mu GST was also tested in female Wistar rats obtained from five
      different sources. Differences in the basal level of class alpha mRNA were
      observed in rats from at least three different sources, while class mu mRNA level
      was distinct in two groups of animals.

PMID- 15497819
TI  - Pro-oxidant activity of zuclopenthixol in vivo: differential effect of the drug
      on brain oxidative status of scopolamine-treated rats.
AB  - Several clinical studies implicated oxidative stress in the pathophysiology of
      both psychosis and dementia. As dementia is commonly associated with psychosis,
      antipsychotic medications are of importance in the pharmacotherapy of dementia
      particularly as a number of antipsychotics were reported to demonstrate neuronal
      pro-oxidant and/or antioxidant properties. Impairment of learning and memory, as
      the most characteristic manifestation of dementia, could be induced in
      experimental animals by acute administration of scopolamine (SCO) with a
      resultant elevation in brain oxidative status. This study investigated the
      potential pro-oxidant and/or antioxidant activity of the antipsychotic drug
      zuclopenthixol acetate, as its effect on brain oxidative status has yet to be
      evaluated. A 2 x 3 between-subjects factorial design was used to investigate the
      simultaneous and interactive effects of zuclopenthixol (0.7 and 1.4 mg/kg i.p.)
      and SCO on rat brain malondialdehyde, glutathione, glutathione peroxidase and
      superoxide dismutase levels/activities. Results revealed a significant pro
      oxidant effect for both zuclopenthixol and SCO alone conditions. In addition,
      combined treatment of zuclopenthixol and SCO was found to be significantly
      different compared to either treatment conditions with regard to their effect on
      different brain oxidative stress indices. Such findings may have valuable
      implications in the pharmacotherapy of both psychosis and dementia.

PMID- 15497820
TI  - Mercury intake by inflammatory phagocytes: in vivo cytology of mouse macrophages
      and neutrophils by X-ray elemental microanalysis coupled with scanning electron
      microscopy.
AB  - Phagocytes remove and store mercury (Hg) that enters the body. Macrophages and
      granulocytes respond in opposite ways to Hg: macrophages loose cell viability,
      and neutrophils become protected from apoptosis. We have investigated the
      cytology of early intake of Hg by macrophages and neutrophils after a short
      period (2-4 min) of in vivo exposure to HgCl2. The two types of phagocytes were
      attracted either to a subcutaneous air pouch or to the peritoneal cavity of
      BALB/c mice by in situ BSA injection. BSA caused, 72 hours later, inflammatory
      exudates where neutrophils (air-pouch cavity) or macrophages (peritoneal cavity)
      were the predominant cell type. A lethal dose of HgCl2 (25 mg) was then injected
      in the two inflammatory cavities. The mice died 2-4 min later and the cell
      exudates were harvested and studied by scanning electron microscopy coupled with
      X-ray elemental microanalysis (SEM-XRM). More than half of the phagocytes showed
      ingested Hg; a higher percentage of macrophages (around 70%) than neutrophils
      (around 50%) were positive for the metal. Intracellular particles of Hg were
      spheroid and presented a small diameter (less than 20 nm). They could be seen in
      large numbers inside phagocytes (up to 20-30 Hg dots per cell); they were
      scattered throughout the cytoplasm of the cells. The ability of phagocytes to
      ingest Hg increased as the BSA-induced inflammation progressed. We conclude that
      (i) Hg is quickly ingested as small particles by phagocytes; (ii) endocytosis of
      Hg increases with the degree of activation of phagocytes; and (iii) phagocytes
      internalize Hg by pinocytosis.

PMID- 15497821
TI  - Antiulcer activity and subacute toxicity of trans-dehydrocrotonin from Croton
      cajucara.
AB  - The antiulcerogenic activity of trans-dehydrocrotonin (DHC), a nor-clerodane
      diterpene isolated from Croton cajucara Benth. (Euphorbiaceae), and its subacute
      (35 days) toxicity were studied in mice and rats, respectively. For the
      antiulcerogenic tests, models of gastric ulcers induced in mice by ethanol/HCl or
      stress were used. In both models, an oral dose of DHC (100 mg/kg) significantly
      reduced (P < 0.01) the formation of gastric lesions. DHC was also tested for its
      ability to scavenge free radicals, but no such action was observed in rat liver
      mitochondria. To assess the subacute toxicity, rats were treated orally with DHC
      (25, 50 and 100 mg/kg) for 5 weeks. A significant increase in liver weight was
      observed in male and female rats at highest doses, whereas a significant
      reduction in plasma alkaline phosphatase and cholesterol levels and an increase
      in gamma glutamyl transpeptidase were observed only at the highest dose (100
      mg/kg) in female rats. DHC caused histopathological alterations in the liver that
      included a turbid tumefaction, microvacuolar degeneration and nuclear
      alterations. Despite the beneficial antiulcerogenic activity of DHC, our results
      suggest that the long-term use of this compound may induce liver damage.

PMID- 15497822
TI  - Removal of endocrine disrupting compounds with membrane processes in wastewater
      treatment and reuse.
AB  - Endocrine disrupting compounds can affect the hormone system in organisms and are
      the subject of environmental and human health concerns. The effluents of
      wastewater treatment plants contribute to the emission of estrogenically active
      substances into the environment. Membrane technology, which is an advanced
      wastewater treatment option, is the subject of this research. The removal
      techniques under investigation are membrane bioreactors, reverse osmosis, and
      nanofiltration. Eleven different nanofiltration membranes were tested in the
      laboratory set-up. The observed retention of NP and BPA ranged between 70% and
      100%. The contact angle is an indicator for the hydrophobicity of a membrane,
      whose influence on the permeability and retention of NP was evident. Regarding
      the retention of BPA no dependency on the contact angle was observed. Results of
      the investigation of a full-scale landfill leachate treatment plant indicate a
      bisphenol A (BPA) removal of more than 98% with membrane bioreactors and reverse
      osmosis. The mass balance indicates that biological degradation is the most
      important removal process in the membrane bioreactor configuration.

PMID- 15497823
TI  - Efficiency of nanofiltration for the elimination of steroids from water.
AB  - Steroid hormones such as the synthetic 17-alpha-ethinylestradiol often persist in
      the sewage treatment process and metabolites of the natural steroids like estrone
      from estradiol accumulate resulting in relevant amounts in the aquatic
      environment. Since biological removal of steroids in the sewage treatment plant
      is not successfully complete, physical processes such as membrane filtration may
      become more important. We investigated the elimination of natural and synthetic
      steroids by nanofiltration using a laboratory membrane reactor. Chemical analysis
      of 17-beta-estradiol, estrone, estriol, 17-alpha-ethinylestradiol, mestranol,
      diethylstilbestrol, progesterone and beta-sitosterine was performed after solid
      phase extraction by GC-MS with standard addition. The elimination rate depended
      on the nanofiltration membrane material. LFC1 membrane consisting of polyamide
      removed the steroids over 99% whereas PES10 membrane consisting of hydrolysed
      polyethersulfone was less efficient, obviously caused by different pore sizes and
      permeability of the membrane structure.

PMID- 15497824
TI  - Removal of hormones and pharmaceuticals in the Advanced Water Recycling
      Demonstration Plant in Queensland, Australia.
AB  - An advanced water recycling demonstration plant was employed to investigate the
      effectiveness of a number of treatment technologies in the removal of some
      residuals of commonly prescribed pharmaceuticals as well as natural and synthetic
      hormones found in sewage. Analysis of targeted compounds was carried out by solid
      phase extraction (SPE) and gas chromatography-mass spectrometry (GC-MS). Initial
      tests were undertaken to determine the background concentrations of the analytes
      during various stages of treatment. Subsequent tests, undertaken by spiking with
      standard solutions of the target compounds provided further information on the
      removal efficiencies of some selected treatment modules. The results of the study
      indicate that while ozonation, microfiltration and nanofiltration were partially
      effective, treatment by reverse osmosis was the most universally successful in
      the removal of the target residuals. While significantly more data is required
      for a full evaluation, this initial investigation suggests that reverse osmosis
      may be an effective means of removing a wider range of pharmaceutically active
      residuals and hormones from treated sewage.

PMID- 15497825
TI  - Effects of advanced oxidation processes (AOPs) on the toxicity of a mixture of
      pharmaceuticals.
AB  - The possibility of applying main AOP techniques, namely ozonation, H2O2/UV
      photolysis and TiO2 photocatalysis to provide a significant reduction of toxicity
      of pharmaceutical mixtures has been evaluated. For the preparation of the mixture
      six pharmaceuticals were chosen among those found at highest concentrations in
      Sewage Treatment Plant effluents, namely carbamazepine, clofibric acid,
      diclofenac, sulfamethoxazole, ofloxacin and propranolol. The blue-green alga
      Synechococcus leopoliensis and the rotifer Brachyonus calyciflorus were utilised
      to assess the toxicity of the mixtures after AOP treatments. All the toxicity
      tests were performed using chronic standardized bioassays. The best results were
      obtained with ozonation. With this type of treatment a complete removal of
      mixture toxicity on S. leopolensis was obtained even after the shortest time of
      application (1 min). The ozonation treatment leads also to removal of all the
      pharmaceutical mixture toxicity on B. calyciflorus, by applying the oxidizing
      agent for at least for 2 minutes.

PMID- 15497826
TI  - Comparison of the behaviour of selected micropollutants in a membrane bioreactor
      and a conventional wastewater treatment plant.
AB  - Micropollutants as pharmaceutical active compounds (PhACs), residuals of personal
      care products or endocrine disrupting chemicals are of increasing interest in
      water pollution control. In this context the removal efficiencies of sewage
      treatment plants (STPs) are of importance, as their effluents are important point
      sources for the release of those substances into the aquatic environment.
      Activated sludge based wastewater treatment is the worldwide prevalently used
      treatment technique. In conventional plants the separation of treated wastewater
      and sludge occurs via sedimentation. A new development is the application of
      membrane technology for this separation step. The studies focus on the influence
      of the solids retention time (SRT) on the removal efficiency, as the SRT is the
      most important parameter in the design of STPs. A conventional activated sludge
      plant (CASP) and a membrane bioreactor (MBR) were operated at different SRTs. The
      substances selected are the antiepileptic carbamazepine, the analgesics
      diclofenac and ibuprofen, the lipid regulator bezafibrate, the polycyclic musks
      tonalide and galaxolide and the contraceptive 17alpha-ethinylestradiole. No
      significant differences in the removal efficiency were detected. Due to the
      absence of suspended solids in the MBR effluent, substances with high adsorption
      potential could be retained to slightly higher amounts.

PMID- 15497827
TI  - Combined chemical analyses and biomonitoring at Avedoere wastewater treatment
      plant in 2002.
AB  - Influent--effluent monitoring by comprehensive chemical analyses was conducted at
      the Avedoere wastewater treatment plant (WWTP) during 2002. In one programme, the
      same samples were tested for algal toxicity by the ISO 8692 method. Based on
      evaluation of 17 hazardous substances (including 7 heavy metals), there was a
      quite good agreement between calculated and measured toxic units. In another
      programme, influent--effluent monitoring for 11 pharmaceuticals and specific
      hormones showed high removal rates, except for sulphamethizol and furosemide.
      High removal is probably due to WWTP operation with long SRTs. Effluent
      biomonitoring of freshwater mussels showed only bioaccumulation for:
      diethylphthalate, LAS, EOX as well as Cr and Ni. Surprisingly, no bioaccumulation
      could be observed for 100 other specific organic compounds and 8 other heavy
      metals (including Hg, Cd and Pb).

PMID- 15497828
TI  - Acclimation of activated sludge to degrade toxic levels of 2,4-dinitrophenol.
AB  - Biodegradation of 75 and 100 mg/l of 2,4-dinitrophenol (DNP) by activated sludge
      acclimated in a Sequencing Batch Reactor (SBR) consistently required less than 6
      hours although a lag at the beginning of every 48-hour SBR cycle was observed.
      Other investigators have reported that DNP levels of 100 mg/l and higher are
      significantly toxic even to acclimated bacteria. The activated sludge acclimated
      to 75 mg/l initial DNP had over 100 times the DNP-degrading bacteria than an SBR
      acclimated to 10 mg/l DNP, although the MLSS concentration in both reactors was
      similar. Results suggest that two mechanisms are responsible for activated sludge
      acclimation to toxic levels of DNP: maintenance of DNP-degrading biomass
      sufficiently large to reduce initial DNP to non-toxic levels, allowing for
      subsequent rapid degradation; and extension of the aeration period well beyond
      the time required for degradation to prevent gradual accumulation of any by
      product which might also be toxic.

PMID- 15497829
TI  - Heavy metal pollution from Russian landfill leachates and its elimination
      together with other contaminants.
AB  - Systematic monitoring of raw leachates (RL) from the operating landfill
      "Khmet'yevo" during December, 2001--June, 2002 with regard to heavy metals (HM)
      revealed that these RL were moderately contaminated with Fe, Zn, Pb and Cd (Cu is
      present in non-dangerous concentrations). This contamination depends on season-
      the winter leachates are less polluted compared to the summer ones. For removal
      of HM together with removal of bulk COD, the UASB reactors were applied where,
      besides elimination of the major part of organic matter, concomitant
      precipitation of HM in the form of insoluble sulphides inside the sludge bed
      occurred due to development of the process of biological sulphate reduction. Both
      removal processes were quite efficient even during operation under submesophilic
      and psychrophilic conditions (20-10 degrees C). The subsequent submesophilic
      aerobic-anoxic treatment of submesophilic anaerobic effluents led to only 75% of
      total inorganic N removal due to COD deficiency for denitrification created by a
      too efficient anaerobic step. On the contrary, psychrophilic anaerobic effluents
      (richer in COD compared to the submesophilic ones) were more suitable for
      subsequent aerobic-anoxic treatment giving the total N removal of 95 and 92% at
      20 and 10 degrees C, respectively. The final effluent is approaching the current
      national standards for direct discharge of treated wastewater.

PMID- 15497830
TI  - A strategy for the assessment of hazardous substances in industrial effluents
      (IDA).
AB  - A strategy for the assessment of industrial wastewater discharges with regard to
      the major hazard parameters toxicity, persistence and bioaccumulation is
      presented. The modular design of the strategy named IDA (Industrial Discharge
      Assessment) allows us to successively determine the three hazard parameters.
      Starting with the parameter toxicity biological tests for acute and chronic as
      well as genotoxicity are performed. Next persistence in the aquatic environment
      is simulated by a biological degradation test. A method based on solid-phase
      extraction was developed to cover the parameter bioaccumulation by determination
      of the amount of potentially bioaccumulating substances. The strategy was applied
      to real wastewater samples to test its applicability. In one of the investigated
      discharges toxic and persistent but no potentially bioaccumulating substances
      were found to be present. The strategy IDA is generally applicable and provides
      reasonable results to allow for a deeper insight into the hazard potential of an
      effluent.

PMID- 15497831
TI  - Combined biological and physico-chemical treatment of baker's yeast wastewater
      including removal of coloured and recalcitrant to biodegradation pollutants.
AB  - The UASB reactor (35 degrees C) was quite efficient for removal of bulk COD (62
      67%) even for such high strength and recalcitrant wastewater as the cultivation
      medium from the first separation process of baker'syeasts (the average organic
      loading rates varied from 3.7 to 10.3 g COD/l/d). The aerobic-anoxic biofilter
      (20 degrees C) can be used for removal of remaining BOD and ammonia from strong
      nitrogenous anaerobic effluents; however, it suffered from COD-deficiency to
      fulfil denitrification requirements. To balance the COD/N ratio, some bypass of
      raw wastewater should be added to the biofilter feed. The application of iron
      chloride coagulation for post-treatment of aerobic effluents may fulfil the
      discharge limits (even for colour mainly exerted by hardly biodegradable
      melanoidins) under iron concentrations around 200 mg/l.

PMID- 15497832
TI  - The effect of nitrogen supplementation on the efficiency of colour and COD
      removal by Malaysian white-rot fungi in textile dyeing effluent.
AB  - White-rot fungi, namely Coriolus versicolor and Schizophyllum commune, were
      studied for the biodecolorization of textile dyeing effluent in shaker-flask
      experiments. The results showed that C. versicolor was able to achieve 68% color
      removal after 5 days of treatment while that of S. commune was 88% in 9 days.
      Both fungi achieved the above results in non-sterile condition with diammonium
      hydrogen phosphate as the nutrient supplement. On the other hand, the best COD
      removal of 80% was obtained with C. versicolor in 9 days in sterile effluent with
      yeast extract as nutrient supplement, while S. commune was able to remove 85% COD
      within 8 days in non-sterile textile effluent supplemented with diammonium
      hydrogen phosphate.

PMID- 15497833
TI  - The case of the nonionic alkylphenol ethoxylates in the Mediterranean Sea region:
      is there a problem?
AB  - The concentration profiles of the potential endocrine disrupting nonionic
      alkylphenol ethoxylate (APEO) surfactants in Israel's rivers, groundwaters and
      coastal water of the eastern Mediterranean Sea, were found to be within the range
      of 12.5-74.6, trace - 20.2 and 4.2-25.0 microg/L respectively. Determination of
      the APEO's homologic distribution revealed "skewing" towards the more toxic
      shorter-chain ethoxylates. Egg production of zebrafish, Danio rerio, exposed to
      these actually found the environmental concentrations range of the APEOs
      decreased, after 20 days, to 89.6+/-2.1, 84.7+/-3.9 and 76.9+/-2.2% of the
      baseline levels, compared with control, in concentrations of 10, 25 and 75
      microg/L respectively. These results suggest that, (a) there is a potential
      health problem, particularly in countries in which the "hard"/environmentally
      persistent APEOs are still in use; and (b) the related health-risk is seasonally
      dependent, particularly in semi-arid regions where the fluctuations in the water
      quantities in surface- and groundwater are substantial.

PMID- 15497835
TI  - Analysis of the transport of cyanide spill on the Tisza River.
AB  - The present paper deals with the wastewater pond accident in Nagybanya (Romania)
      in 2000 of which the result was an about 100 tons of highly toxic cyanide spill
      into the River Tisza. Measurements and laboratory tests were performed during the
      toxic wave transport. On the basis of this data set mass balance calculations
      were performed by hydraulic and transport models to investigate and better
      understand the effect of the accident and to calculate the possible heavy metal
      sedimentation process in Tisza River bed. This paper deals with calculations for
      cyanide and copper which are mostly associated to cyanide pollution.

PMID- 15497834
TI  - BTE-OX biodegradation kinetics with MTBE through bioaugmentation.
AB  - The biodegradation kinetics of BTE-oX and MTBE, mixed all together, in the
      presence of bioaugmented bacterial populations as high as 880 mg/L VSS was
      evaluated. The effect of soil in aqueous samples and the effect of Tergitol NP-10
      on substrate biodegradation rates were also evaluated. Biodegradation kinetics
      was evaluated for 36 hours, every 6 hours. Benzene and o-xylene biodegradation
      followed a first-order one-phase kinetic model, whereas toluene and ethylbenzene
      biodegradation was well described by a first-order two-phase kinetic model in all
      samples. MTBE followed a zero-order removal kinetic model in all samples. The
      presence of soil in aqueous samples retarded BTE-oX removal rates, with the
      highest negative effect on o-xylene. The presence of soil enhanced MTBE removal
      rate. The addition of Tergitol NP-10 to aqueous samples containing soil had a
      positive effect on substrate removal rate in all samples. Substrate percent
      removals ranged from 95.4-99.7% for benzene, toluene and ethylbenzene. O-xylene
      and MTBE percent removals ranged from 55.9-90.1% and 15.6-30.1%, respectively.

PMID- 15497836
TI  - Development of automated high-throughput ecotoxicity and genotoxicity test
      systems and fields of application.
AB  - Bioassays like growth inhibition and genotoxicity assays are frequently used for
      the characterization of chemicals and contaminated environmental samples. In this
      work two standardized bioassays are automated completely using newly developed
      liquid handling stations and robotics. A high-throughput algal growth inhibition
      assay prototype is set up and optimized in cooperation with Hoelle & Huettner AG
      (Tuebingen, Germany) and Polygen GmbH (Langen, Germany). A software package for
      both the control of the test system and for data evaluation has been developed
      (Biolane Supervisor, BioLane Manager HTT). The applicability of the prototype is
      demonstrated by testing reference compounds with the automated assay in parallel
      with the Erlenmeyer flask assay. It is shown that EC50-values of chemicals do not
      differ significantly when incubation parameters like homogeneity of light
      intensity, temperature and evaporation during 72 hours of incubation are
      optimized. The umu-genotoxicity test is automated completely using a "RoboSeq
      4204 SE" pipetting station (MWG AG, Ebersberg, Germany) equipped with two
      shakers, microplate photometer, four pipettes, stacker for ten microplates and
      incubation cabin with temperature regulation. As a result of miniaturization and
      automation large numbers of toxicants and far more treatments and parallels can
      be tested and, additionally, only low sample volumes are needed.

PMID- 15497837
TI  - Derivatisation of 4-nonylphenol and bisphenol A with halogenated anhydrides.
AB  - The aim of this work is to synthesize and characterise the halogenated
      derivatives of the endocrine disrupting compounds (EDCs) 4-nonylphenol (4-NP) and
      bisphenol A (BPA). Characterisation was performed after gas chromatographic (GC)
      separation on-line coupled to mass spectrometric (MS) detector and a Fourier
      Transform Infrared (FTIR) spectroscopic detector. Further structure elucidation
      was done applying Nuclear Magnetic Resonance spectroscopy (NMR). Two different
      approaches for the preparation of derivatives were evaluated. At first
      trifluoroacetyl derivatives were synthesized by the reaction of trifluoroacetic
      acid (TFA) anhydride and the EDCs in acetonitrile at a temperature of 50 degrees
      C for 30 minutes. In a second step the 4-NP was derivatised using trichloroacetic
      acid anhydride and triethylamine in diethyl ether at 20 degrees C for 30 minutes.
      After synthesis the halogenated NP and BPA derivatives were characterised
      applying GC/MS, GC/FTIR and NMR. Three indices for a successful derivatisation
      were observed: El-GC/MS proved a complete derivatisation presenting a
      characteristic fragmentation pattern for each derivative. The IR spectra obtained
      by GC/FTIR after derivatisation and separation confirmed the loss of the phenolic
      O-H stretching vibration at 3,600 cm(-1) while typical absorptions for
      halogenated compounds now were observed. The NMR-spectra contained the predicted
      resonance signals.

PMID- 15497838
TI  - Determination of musks and other fragrance compounds at ng/L levels using CLSA
      (closed loop stripping analysis) and GC/MS detection.
AB  - Closed loop stripping analysis (CLSA), a suitable tool for the determination of
      volatile and semivolatile compounds at low trace levels (ng/l), has been used to
      determine and quantify seven selected musks and two fragrances (Acetyl cedrene
      and Amberonne). The obtained extracts are analyzed by high resolution gas
      chromatography coupled to mass spectrometry (GC/MS) operating in the SIM mode.
      Quality parameters such as limit of detection; matrix effects; precision
      expressed as repeatability and reproducibility relative standard deviations of
      the method and an estimation of the uncertainty have been evaluated. The method
      has been applied to the analysis of wastewater effluents, surface water and tap
      water from different places in Europe. All samples contained differents musks at
      ng/l levels with the polycyclic musks Galaxolide and Tonalide and both
      fragrances, Amberonne and Acetyl cedrene, being the most abundant. These results
      suggest the importance of studying and controlling the presence of these
      ubiquitous environmental compounds in water systems.

PMID- 15497839
TI  - The effect of bisphenol A and chlorinated derivatives of bisphenol A on the level
      of serum vitellogenin in Japanese medaka (Oryzias latipes).
AB  - 2,2-bis (4-hydroxyphenyl) propane or Bisphenol A (BPA), has been reported to
      behave as an endocrine disrupter below acute toxic levels, and is widely present
      in the water environment. Although BPA is easily chlorinated, very little is
      reported on the effect of chlorinated BPA to the aquatic organisms. In this
      study, the estrogenic activities of BPA and its chlorinated derivatives were
      evaluated by the induction of vitellogenin (VTG) in the serum of mature male
      Japanese medaka. In addition, the effect of sodium hypochlorite on the
      decomposition of BPA was tested. The relative potencies of estrogenic activities
      of chlorinated BPA descended in the order 3,3'-diCIBPA>BPA> or =3-CIBPA>3,3',5
      triCIBPA, and no estrogenic activity was observed in 3,3',5,5'-tetraCIBPA. Lowest
      Observed Effect Concentration (LOEC) and No Observed Effect Concentration (NOEC)
      for both 3-CIBPA and 3,3'-diCIBPA were 500 microg/L and 200 microg/L,
      respectively. LOEC for 3,3',5-triCIBPA was >500 microg/L. When BPA was reacted
      with sodium hypochlorite (24 hours; residual chlorine at 1 ppm), however,
      complete decomposition of BPA and its chlorinated derivatives was observed. The
      decrease in BPA and its chlorinated derivatives paralleled the decrease in
      estrogenic potency evaluated by the induction of vitellogenin (VTG) in the serum
      of mature male Japanese medaka.

PMID- 15497840
TI  - Behaviour of endocrine disrupting chemicals during the treatment of municipal
      sewage sludge.
AB  - Agricultural application of municipal sewage sludge has been emotionally
      discussed in the last decades, because the latter contains endocrine disrupting
      chemicals (EDCs) and other organic micropollutants with unknown fate and risk
      potential. Bisphenol A (BPA) was chosen as a model substance to investigate the
      influence of sludge conditioning on the end-concentration of EDCs in sludge.
      Adsorption studies with radioactive-labelled BPA showed that more than 75% BPA in
      anaerobically digested sludge is bound to solids (log Kd = 2.09-2.30; log Koc =
      2.72-3.11). Sludge conditioning with polymer or iron (III) chloride alone had no
      influence on the adsorption of BPA. After conditioning with iron (III) chloride
      and calcium hydroxide desorption of BPA took place. Apparently, it occurred due
      to the deprotonation of BPA (pKa= 10.3) as the pH-value reached 12.4 during the
      process. The same behaviour is expected for other phenolic EDCs with similar pKa
      (nonylphenol, 17beta-estradiol, estron, estriol, 17alpha-ethinylestradiol). This
      study shows high affinity of BPA to the anaerobically digested sludge and
      importance of conditioning in the elimination of EDCs during the sludge
      treatment. Addition of polymer is favourable in the case of sludge incineration.
      Conditioning with iron (III) chloride and calcium hydroxide shows advantages for
      the use of sludge as fertiliser.

PMID- 15497841
TI  - Behaviour of bisphenol A (BPA), 4-nonylphenol (4-NP) and 4-nonylphenol
      ethoxylates (4-NP1EO, 4-NP2EO) in oxidative water treatment processes.
AB  - Endocrine disrupting chemicals (EDCs) such as natural and synthetic hormones or
      industrial chemicals can adversely affect the endocrine system at very low
      concentrations. As such substances can be present in raw water used for drinking
      water production, they potentially pose a health risk to humans. In this study
      laboratory tests were performed to determine removal efficiencies of selected
      oxidative drinking water treatment processes, namely ozonation (1.4 mg/l O3) and
      chlorination, using sodium hypochlorite (0.5 mg/l NaClO) and chlorine dioxide
      (0.4-0.6 mg/l ClO2) under conditions applied in technical plants. 500-300,000
      ng/l of bisphenol A (BPA), 4-nonylphenol (4-NP) and 4-nonylphenol-n-ethoxylates
      (NPnEO) were selected for investigations and measured by HPLC/FLD and HPLC/MS. To
      investigate possible oxidation by-products, adsorbable organic halogens (AOX)
      were determined and estrogenic activities were assessed with the help of an
      estrogen receptor binding assay (YES). Ozonation and chlorination with ClO2
      removed both 4-NP and BPA below detection limits, corresponding with AOX and
      estrogenic activity. Concerning NPnEO ozonation removed NP1EO and NP2EO up to 28%
      and 30%, respectively, whereas ClO2 showed high removal efficiencies, eliminating
      >94% and 92%, respectively. NaCIO removed 4-NP and BPA below detection limits,
      but estrogenic activities increased and AOX could be measured. NP1EO and NP2EO
      were only marginally reduced corresponding to the slight decrease of estrogenic
      potential.

PMID- 15497842
TI  - Relevance of the sludge retention time (SRT) as design criteria for wastewater
      treatment plants for the removal of endocrine disruptors and pharmaceuticals from
      wastewater.
AB  - Wastewater treatment plants (WWTPs) represent a significant source for the input
      of micro pollutants as endocrine disruptors (EDs) or pharmaceutically active
      compounds (PhACs) into the aquatic environment. Treatment efficiency of WWTPs
      often is reported, taking into account only inflow and effluent concentrations
      without further specification of the WWTP investigated. In order to allow
      comparison and evaluation of the removal efficiency of different layouts and
      concepts in wastewater treatment, additional information like the sludge
      retention time (SRT) and sludge load (F/M ratio) are necessary. Presented results
      from different WWTPs show correlation of removal of EDs and PhACs to the SRT.
      Compared to WWTPs with high F/M ratio implementation of the nitrification process
      on WWTPs results in a significant increase of the removal efficiency for EDs and
      PhACs. This paper describes an approach to determine comparable removal rates for
      different activated sludge systems based on mass balance and SRT.

PMID- 15497843
TI  - Analysis of nonylphenol polyethoxylates and their metabolites in water samples by
      high-performance liquid chromatography with electrospray mass spectrometry
      detection.
AB  - Evidence that some alkylphenol polyethoxylates (APEOs) breakdown products are
      estrogenic has intensified the interest over their environmental and human health
      effects. Different quantitative methods but one single preparation and extraction
      method for the analysis of nonylphenol polyethoxylates (NPEOs) and their
      metabolites in water samples using solid-phase extraction (SPE) and high
      performance liquid chromatography (HPLC) with electrospray mass spectrometry
      detection (ESI-MS), are described. Quantification limits range about the low ng/l
      for the enrichment of 500 ml water samples and mean recoveries of 70% are
      achieved. These methods were subsequently applied to water samples coming from
      Austrian treatment plants.

PMID- 15497844
TI  - Mass spectrometric analytical methods for the determination of endocrine
      disrupting chemicals (EDCs).
AB  - This paper describes a method for the determination of endocrine disrupting
      chemicals (EDCs) in waste water. The method involves a SPE-C18 extraction
      followed by a SPE-silica gel column clean up and elution of the analytes with a
      mixture of acetone/pentane (2+1). Thereafter derivatisation of the analytes with
      heptafluorobutyric acid anhydride (HFBA) and analysis by gas chromatography/mass
      spectrometry (GC/MS) with positive electron impact ionisation (EI) or negative
      chemical ionisation (NCI) using methane as reactant gas was performed. The two
      different ionisation techniques were compared and the negative chemical
      ionisation technique proved significant lower limits of detection (LODs) and
      quantitation (LOQs) than positive electron impact ionisation. Recoveries of the
      analytes in various spiked waste water samples ranged from 75.4 to 96.9%. The
      concentrations of the EDCs in feed waste water from three different waste water
      treatment plants (WWTPs) ranged from non-detectable up to a concentration of
      10,305 ng/L for 4-NP and in the corresponding effluent samples from non
      detectable to 723 ng/L for BPA.

PMID- 15497845
TI  - Distribution of estrogen, nonylphenol and its derivatives in the sediments of a
      shallow lake.
AB  - To determine the distribution of endocrine disruptors (EDs) in lake water and
      sediments, field investigation was conducted in Lake Teganuma, which is a shallow
      eutrophic lake, highly affected by human activities. Concentration profiles with
      sediment depths were obtained for estrogens, nonylphenol (NP), nonylphenol
      ethoxylates (NPnEO), and nonylphenoxy acetic acids (NPnEC). 17beta-Estradiol (E2)
      was rarely detected, and 17alpha-ethynylestradiol (EE2) and estriol (E3) were
      undetected at all depths (0-98 cm) in any of the sediment core samples. The
      sediment concentrations of estrone (E1) ranging from <0.05 to 3.5 microg/kg-dry
      wt. and NP from 11.8 microg/kg-dry wt. to 21 mg/kg-dry wt. were obtained. The
      maximum concentrations of NPnEO and NPnEC in the core sediments were 2.5 mg/kg
      dry wt. and 1.4 mg/kg-dry wt., respectively. The EDs concentrations are higher at
      the inlet than at the outlet (except for NP) in the sediments near the surface.
      The longitudinal distributions of E1, NPnEO and NPnEC in the benthic sediments
      show that the concentrations are highest at the inlet, and are fairly constant at
      lower levels towards the downstream. The obtained results also indicate that NP
      tends to be adsorbed to the organic particulates produced by algae, followed by
      sedimentation near the outlet of the lake.

PMID- 15497846
TI  - Assessing the elimination of estrogenic activity in advanced wastewater treatment
      with a reporter gene-based bioassay.
AB  - Estrogen-like chemicals, so-called xenoestrogens, have become a topic of concern
      because they are potentially capable of disturbing the hormonal balance of
      wildlife and humans. Effluents of wastewater treatment plants (WWTPs) are
      presumably the major source of xenoestrogens in the aquatic environment. In this
      study, we investigated eight WWTPs with respect to their input, elimination
      efficiency, and output of estrogenic activity by means of a reporter gene-based
      bioassay. All WWTPs employed activated sludge treatment with
      nitrification/denitrification and tertiary treatment (second nitrification and/or
      filtration). Estradiol equivalents (EEQs) in the influents of the WWTPs were
      between 5.7 and 65.8 ng/L. The greatest inputs were found in plants treating pure
      domestic sewage and in samples collected in winter. Process waters either had no
      estrogenic activity or EEQs in the range of raw sewage, depending on the source
      of the process water. EEQs of effluents ranged from mostly below quantification
      limit (0.8 ng/L) to a maximum of 5.4 ng/L in secondary and 1.4 ng/L in tertiary
      effluents. These findings demonstrate the elimination efficiency of the activated
      sludge treatment and the further improvement by additional tertiary treatment.
      However, several concentrated effluents elicited little, but detectable
      estrogenic responses in the bioassay.

PMID- 15497847
TI  - Microbial degradation of a single branched isomer of nonylphenol by Sphingomonas
      TTNP3.
AB  - The endocrine disrupting chemical nonylphenol (NP) is a technical product which
      consists of a complex mixture of nonylphenols with different alkyl side-chain
      isomers. Since the bio-degradation of each NP isomer may lead to its own range of
      metabolites, the isolation and identification of transformation products is very
      difficult. In order to overcome this difficulty, the nonylphenol isomer 4(3',5'
      dimethyl-3'-heptyl)-phenol (p353NP) was synthesized, and its degradation by an
      axenic culture of Sphingomonas TTNP3 was investigated with [ring-U-14C]-labelled
      and non-labelled p353NP including a time-course study. Radioactive mass balancing
      resulted in different polar soluble fractions, in insoluble radioactivity
      associated with biomass, and volatile radioactivity in the form of the
      mineralization product 14CO2. In the extracellular media, the presence of nonanol
      corresponding to the nonyl chain of the NP isomer was confirmed and its
      concentration was determined during the course of fermentation. No other
      radioactive compounds were detected beside the parent isomer. Radioactive
      metabolites were only found in the intracellular fraction of S. TTNP3.

PMID- 15497848
TI  - Removal of persistent polar pollutants through improved treatment of wastewater
      effluents (P-THREE).
AB  - The EU-project P-THREE started with the establishment of analytical methods for
      persistent polar pollutants (P3) and quality assurance, followed by screening of
      P3 in influents and effluents of known wastewater (WW) treatment plants (TP),
      receiving waters and tap water produced thereof in several European countries. A
      final selection of analytes for further studies has been performed. Model MBR
      reactors have been constructed and an optimisation on synthetic wastewater spiked
      with P3 (linear alkylbenzene sulfonates (LAS), naphthalene sulfonates) has been
      performed. An initial dynamic modelling of treatment processes has also started.
      Advanced oxidation process (AOP) treatment has been done in groundwater with
      isoproturon and nonylphenol ethoxylates (NPEO). The analysis of individual P3 and
      potential degradation products was also performed. An integrated systeme analysis
      of the WW treatment processes has also been initiated.

PMID- 15497849
TI  - Occurrence of benzothiazoles in municipal wastewater and their fate in biological
      treatment.
AB  - A number of 2-substituted benzothiazoles that are known to be used as fungicides,
      corrosion inhibitors and vulcanization accelerators in industry have been
      analyzed in municipal wastewater and the effluents of activated sludge and
      membrane bioreactor (MBR) treatment over a three month period. All six analytes
      were regularly detected in the municipal wastewater by liquid chromatography-mass
      spectrometry and amount to a total concentration of 3.4 microg/L. Of these
      compounds benzothiazole-2-sulfonic acid (1,700 ng/L), benzothiazole (850 ng/L)
      and 2-hydroxybenzothiazole (500 ng/L) were most prominent. The source of the
      benzothiazole emission is yet unknown. Activated sludge treatment did not reduce
      total benzothiazole concentration significantly. Removals of the individual
      compounds ranged from 90% for 2-mercaptobenzothiazole and 70% for
      hydroxybenzothiazole to 40% for benzothiazole. The concentration of benzothiazole
      2-sulfonic acid increased by 20%, whereas 2-methylthiobenzothiazole increased by
      160% during activated sludge treatment, likely due to the methylation of
      mercaptobenzothiazole. Total benzothiazole removal in two parallely operated MBRs
      was significantly better (43%) than in the conventional activated sludge
      treatment. Namely benzothiazole and benzothiazole-2-sulfonic acid were more
      effectively removed. This first systematic study on the occurrence of
      benzothiazoles in municipal wastewater has shown that this is a relevant class of
      trace contaminants in municipal wastewater which is only incompletely removed in
      biological wastewater treatment. Emission from sewage treatment is dominated by
      the most polar benzothiazole-2-sulfonic acid. MBR treatment may reduce but cannot
      avoid this emission.

PMID- 15497850
TI  - Modelling the degradation of low concentration pollutants in membrane
      bioreactors.
AB  - This paper deals with the development of a description of membrane bioreactor
      systems, focussing on wastewater treatment and removal of specific low
      concentration persistent organic pollutants (e.g. persistent polar pollutants--P3
      compounds). In the present work we offer a basic model, adapted to Membrane
      Bioreactor (MBR) conditions, which reflects the biodegradation of recalcitrant
      (organic) substances. We put a particular focus on organic aromatic pollutants
      and demonstrate a model parameter estimation approach, with experiments carried
      out for linear alkylbenzene sulphonates (LAS).

PMID- 15497851
TI  - Comparison of linear alkylbenzene sulfonates removal in conventional activated
      sludge systems and membrane bioreactors.
AB  - The potential of a membrane bioreactor (MBR) and a conventional activated sludge
      (CAS) system to remove polar micropollutants was evaluated using linear
      alkylbenzene sulfonates (LAS) as model components. Removal efficiencies over 97%
      were achieved in both reactor systems. The appearance of biological breakdown
      metabolites and the respirometric response of the sludges to LAS addition
      indicated that LAS removal was due to biodegradation, rather than sorption
      phenomena. The effect of operational variables, such as hydraulic retention time,
      LAS composition and hydrophobicity of the membrane used in the MBR, was
      negligible in the range tested. A stepwise increase in LAS influent concentration
      resulted in higher residual effluent concentrations but did not change the
      procentual removal efficiency. Because an increase in LAS and SPC effluent
      concentration occurred to a larger extent in the CAS than in the MBR under
      similar operating conditions, MBRs may turn out to be be more robust with respect
      to biological degradation of micropollutants than CAS.

PMID- 15497852
TI  - LC-MS-(MS) determination of oxidative degradation products of nonylphenol
      ethoxylates, carboxylates and nonylphenols in water.
AB  - A commercial blend of nonylphenol ethoxylates (NPEOs) was chosen as
      representative for non-ionic polyethoxylated surfactants to study the oxidative
      degradation of this class of surfactants in water using ozonation as well as
      electron beam irradiation with and without the addition of ozone as treatment
      processes. The electron beam irradiation processes applied represent so-called
      Advanced Oxidation Processes (AOPs); the combined ozone/electron beam irradiation
      is, moreover, the most powerful AOP which can be applied in aqueous systems. It
      was found that both ozonation and the two AOPs applied were able to decompose not
      only the NPEOs but also the polyethyleneglycoles (PEGs) formed as by-products
      from NPEO degradation to residual concentrations below the limit of detection.
      Moreover, the treatment processes were also used to study the oxidative
      degradation of nonylphenoxy acetic acid (NPEC) and of nonylphenol (NP) which are
      formed as by-products from biodegradation of NPEOs.

PMID- 15497853
TI  - Perfluorooctane sulfonate--a quite mobile anionic anthropogenic surfactant,
      ubiquitously found in the environment.
AB  - The biochemical degradation of perfluorooctanesulfonate (PFOS) and
      perfluorooctanoic acid (PFOA) under aerobic and anaerobic conditions in closed
      loop systems was monitored in laboratory scale. Adsorptive effects of these
      compounds to glass and polypropylene were also examined. Liquid
      chromatography/mass spectrometry (LC-MS) under negative electrospray (ESI(-))
      conditions was applied for determination. Elimination of PFOS was observed under
      anaerobic conditions whereas aerobic treatment was not effective.

PMID- 15497854
TI  - Integrated systems analysis of persistent polar pollutants in the water cycle.
AB  - Persistent polar pollutants (P3) are difficult to degrade in standard waste water
      treatment plants. As a result, they end up in the effluent and are emitted to the
      surface water. In some areas, this problem is aggravated through "closed loop
      recycling", causing concentrations of P3 in surface water to build up over time.
      This could cause violation of (future) EU regulations. In the P-THREE project,
      various alternative waste water treatment techniques are investigated regarding
      their effectiveness in eliminating these substances, especially membrane
      bioreactor treatment and advanced oxidation processes, MBR and AOP. The
      integrated systems analysis which is the subject of this paper assesses these
      techniques in a broader systems context: (1) the life-cycle of the P3, (2) the
      life cycle of the WWTPs, and (3) the WWTP life cycle costs.

PMID- 15497855
TI  - Removal of selected non-steroidal anti-inflammatory drugs (NSAIDs), gemfibrozil,
      carbamazepine, beta-blockers, trimethoprim and triclosan in conventional
      wastewater treatment plants in five EU countries and their discharge to the
      aquatic environment.
AB  - The removal of commonly used pharmaceuticals (ibuprofen, naproxen, diclofenac,
      gemfibrozil, carbamazepine, atenolol, metoprolol and trimethoprim) and a biocide
      (triclosan) in operating wastewater treatment plants in five EU countries has
      been studied. Under normal operating conditions the acidic drugs and triclosan
      were partially removed with removal rates varying from ca. 20 to >95%. The
      highest removal rate was found for ibuprofen and triclosan (>90%) followed by
      naproxen (80%), gemfibrozil (55%) and diclofenac (39%). Ibuprofen undergoes an
      oxidative transformation to corresponding hydroxy- and carboxy-metabolites, which
      contributes to its high removal rate. Disturbances in the activated sludge
      process resulted in lower removal rates for all acidic drugs, mostly for
      diclofenac (<10% removed) but also for ibuprofen (<60% removed). The treatment of
      wastewaters by activated sludge usually did not result in any practical removal
      (<10%) of neutral carbamazepine or basic atenolol, metoprolol and trimethoprim.
      The removal rates of the investigated drugs and triclosan are discussed in terms
      of mechanisms responsible for their removal. Discharges of carbamazepine,
      diclofenac, gemfibrozil, naproxen, triclosan and trimethoprim from WWTPs to the
      aquatic environment, expressed as the average concentration in the effluent and
      the daily discharged quantity per person served by WWTPs were assessed.

PMID- 15497856
TI  - Bank filtration: a suitable process for the removal of iodinated X-ray contrast
      media?
AB  - After bank filtration, effluent influenced surface waters are often used as raw
      drinking water. It is known that high concentrations of iodinated X-ray contrast
      media are detectable in such surface waters and thus, more knowledge about the
      behaviour of the contrast media during bank filtration is necessary and the
      subject of investigations in this study. The adsorbable organic iodine (AOI),
      four widely used iodinated X-ray contrast media and four possible transformation
      products were quantified in an influenced lake, five groundwater wells and a
      drinking water well. Under anoxic conditions the AOI as well as the concentration
      of the contrast media are decreased by bank filtration, whereby the AOI is
      decreased by 64% and the contrast media concentration can be reduced up to 95%,
      depending on the compound. In the raw drinking water the following average
      concentrations were determined: lopromid < 20 ng/L, Diatrizote 166 ng/L,
      lopamidol 166 ng/L and lohexol 34 ng/L. Instationary conditions during the
      sampling period indicate that, at least under anoxic conditions, a large part of
      the contrast media and transformation products, which are still iodinated, may be
      associated to colloids and/or humic material.

PMID- 15497857
TI  - Carbamazepine, diclofenac, ibuprofen and bezafibrate--investigations on the
      behaviour of selected pharmaceuticals during wastewater treatment.
AB  - Numerous investigations in different European countries observed various
      pharmaceutically active compounds (PhACs) in notable concentrations in the
      aquatic environment. Further determinations found the effluents of sewage
      treatment plants (STPs) to be significant sources for the entry of pharmaceutical
      residuals to rivers, streams and surface waters. Due to those pathways the
      knowledge about the elimination of these substances and their behaviour in
      wastewater treatment plants (WWTP) is elementary for protection of an intact
      aquatic environment. Since the sludge retention time (SRT) is the most important
      parameter for the design of STPs, its influence on the reduction rate of these
      PhACs in the wastewater treatment process was investigated. To study this
      influence of the SRT on the elimination of PhACs, lab scale plants have been
      operated with different sludge retention times. The results of the laboratory
      experiments have been validated analysing various STPs within a wide capacity
      range and operating at different SRTs. This report describes the determinations
      observed on the antiepileptic drug Carbamazepine, the two antiphlogistics and
      analgesics Diclofenac and Ibuprofen and the lipid regulator Bezafibrate.

PMID- 15497858
TI  - Bioavailability of a nonylphenol isomer in dependence on the association to
      dissolved humic substances.
AB  - Humic substances are important environmental components since they represent a
      very large part of organic compounds on earth. According to many reports,
      dissolved humic substances are a determinant parameter for the bioavailability of
      xenobiotic compounds. For the present bioavailability studies, two kinds of
      dissolved humic substances, a commercially available humic acid and fulvic acids
      isolated from peat were used. As the relevant xenobiotic, a defined branched
      nonylphenol isomer, 4(3',5'-dimethyl-3'-heptyl)-phenol (p353NP) was synthesised
      according to Friedel-Crafts alkylation. Equilibrium dialysis studies were
      implemented in order to investigate the association between 14C-labelled p353NP
      and dissolved humic substances. The biodegradability in the presence of dissolved
      humic substances was examined in experiments with the nonylphenol degrading
      bacterium strain Sphingomonas TTNP3 and with p353NP as sole carbon source. The
      results showed that p353NP-humic acid associates were formed in high amounts,
      whereas no adducts with fulvic acids occurred. In the degradation studies with
      Sphingomonas TTNP3, no effects of dissolved humic substances on the
      bioavailability of p353NP could be observed. It was assumed that the association
      between nonylphenol and humic acids occurs rapidly and is reversible. Thus, the
      formation of "labile" complexes did not influence biodegradation rates, which
      were quite low.

PMID- 15497859
TI  - Assessment of ecological status in small urban streams of Prague agglomeration.
AB  - The purpose of this research was to compare ecological status of a few small
      urban watersheds in Prague agglomeration (the Botic creek, the Zatissky creek and
      the Komoransky creek) with different sources of pollution, different sewer
      systems and with different hydraulic regimes of the recipient. Concentrations of
      selected heavy metals (Cd, Cu, Ni, Pb, Zn) were measured in water and sediment
      samples and in different species of benthic organisms. The biological assessment
      of macrozoobenthos has also been carried out using two biotic indexes: the
      saprobic index and the ASPT. The assessment of the environmental risk in an
      aquatic environment has been based on three different coefficients: the
      Distribution coefficient (Kd), the Hazard Quotient (HQ) and the Metal Pollution
      Index (MPI). In the Botic creek there was found out chronic load of bottom
      sediment by heavy metals. There is higher ecological risk of sediment toxicity in
      this creek. Outlets of combined sewer system in the Botic creek degrade water
      quality and consequently deteriorate biological indicators. In the Zatissky creek
      the main problem is connected with storm sewer outlets. The comparison of the
      Zatissky creek with the reference stream, the Komoransky creek demonstrates
      strong hydraulic impact, which induces frequent changes of watercourse morphology
      reflecting on the composition and representation of benthic macroorganisms.

PMID- 15497860
TI  - Endocrine disrupters in the aquatic environment: the Austrian approach--ARCEM.
AB  - A consortium of Austrian scientists (ARCEM) carried out a multidisciplinary
      environmental study on Austrian surface and ground waters including chemical
      monitoring, bioindication, risk assessment and risk management for selected
      endocrine disrupters: 17beta-estradiol, estriol, estrone, 17alpha
      ethinylestradiol, 4-nonylphenol, 4-nonylphenol ethoxylates (4-NP1EO, 4-NP2EO) and
      their degradation products, ocytlphenol, ocytlphenol ethoxylates (OP1EO, OP2EO)
      as well as bisphenol A. To obtain data representative for Austria, a material
      flow analysis served to select relevant compounds and water samples were
      collected monthly over one year at those sites routinely used in Austrian water
      quality control. The following results were obtained and conclusions drawn: 1.
      Chemical monitoring: As compared to other countries, relatively low levels of
      pollution with endocrine disrupters were detected. 2. Bioindication: In the
      surface waters under study, male fish showed significant signs of feminization
      and demasculinization (increased production of the egg-yolk protein and
      histological changes of the gonads. 3. Risk assessment: For humans, exposure via
      either drinking water abstraction (ground water) or fish consumption was
      considered. The exposure levels of the compounds under study were below those
      considered to result in human health risks. Likewise, for bisphenol A and
      octylphenols, there was no indication for risk posed upon the aquatic environment
      (fish). However, nonylphenol or 17alpha-ethinylestradiol exposure along with
      results of bioindication (2) suggest a borderline estrogenic activity in a
      considerable number of surface waters. Consequently the emissions of these
      substances into the surface waters affected have to be reduced. 4. Risk
      management: Waste water treatment experiments revealed a positive correlation
      between the removal rate of endocrine disrupters from the waste water and the
      sludge retention time in the treatment plants. These substances are removed to a
      higher extend at low loaded plants designed for nutrient removal than at plants
      that remove carbon and/or employ nitrification only. As to drinking water
      treatment, chlorine dioxide and ozone were found to eliminate all investigated
      substances, except nonylphenol ethoxylates. (For the complete study see:
      www.arcem.at)

PMID- 15497861
TI  - Analysis and fate of insect repellents.
AB  - During summer months the insect repellent N,N-diethyl-m-toluamide (DEET) could
      always be detected in influents and effluents of wastewater treatment plants
      (WWTP) and anthropogenically influenced surface waters. In Germany the
      concentrations have decreased constantly since 1999, when DEET was substituted by
      Bayrepel. DEET can be degraded in WWTP, but only after an adaptation period and
      values in the influent above the threshold value. Since the year 2000 Bayrepel
      could also be detected during the summer months in the influents of WWTP, whereas
      in the effluents Bayrepel was not present.

PMID- 15497862
TI  - The Elbe flood in August 2002--occurrence of polychlorinated dibenzo-p-dioxins,
      polychlorinated dibenzofurans (PCDD/F) and dioxin-like PCB in suspended
      particulate matter (SPM), sediment and fish.
AB  - As a result of extreme precipitation in August 2002 major flooding occurred in
      the catchment area of the rivers Elbe, Vltava (Moldau) and Mulde. Pollutants from
      industrial sites and from municipal sewage treatment works (STW) entered the Elbe
      and led to a serious pollution problem in the river. PCDD/F concentrations (in pg
      WHO-TEQ/g dw) in SPM ranged from 7-150, in sediments from 3-140; the "safe
      sediment value" of 20 was exceeded in 46% of the samples. 24 eels showed a wide
      concentration variation for these contaminants. The WHO-PCDD/F+PCB-TEQ values lay
      in the range from 11-56 pg/g ww, whereby the WHO-PCB-TEQ values were several
      times higher than the WHO-PCDD/F-TEQ values. The maximum permitted value of 4 pg
      WHO-PCDD/F/g ww (EU Directive No. 2375/2001) was reached or exceeded in 54% of
      the individuals. A statistical analysis using data from SPM and sediment samples
      showed that in the Czech river section the flooding activated a contamination
      source in the vicinity of the Spolana works. The influence of the tributary Mulde
      could be clearly demonstrated. Only a major clean-up of the contaminated sites in
      Bitterfeld can lead to a mid to long term improvement in respect of PCDD/F and
      dioxin-like PCB input into the Elbe.

PMID- 15497863
TI  - Contamination of sediments in Varna Lake and Varna Bay.
AB  - Varna Bay is one of the hot spots along the Black Sea coastal zone. Its
      ecological state is strongly influenced by the connection with the Varna Lake.
      Along the lake coast are located many sources of pollution such as rivers, ports,
      chemical industry, WWTPs. The shipping is another pressure on the environment.
      The study was carried out in the western part of the Varna Lake and Varna Bay.
      The following parameters: heavy metals, polichlorinated biphenyls, chlororganic
      pesticides, phenols, petroleum hydrocarbons were analysed in sediments. The high
      content of the last one is indicative for an extremely unfavourable long-year
      exploitation of the lake as a water route. The metals concentration in lakes
      sediments shows the influence of anthropogenic inputs. Comparative analysis of
      the sediments shows higher concentrations of contaminants in Varna Lake. and near
      the ports. As a consequence of the worsened state of the bottom a very poor
      benthic community characterizes a part of the investigated area in the lake.

PMID- 15497864
TI  - Contribution of brominated organic disinfection by-products to the mutagenicity
      of drinking water.
AB  - The activity inducing chromosomal aberrations of the mixture of brominated
      disinfection by-products (DBPs) was approximately three times higher than that of
      the chlorinated counterparts for the same hypohalous acid dose. With the
      combination of chromosomal aberration test and a new analytical technique to
      differentiate total organic chlorine (TOCl) and total organic bromine (TOBr), it
      was found that TOBr was correlated to the mutagenicity of chlorinated waters. It
      was also implied that for a bromide-to-TOC ratio of 0.1 (mg/mg C), brominated
      DBPs could account for at least 29% of the total toxicity of DBPs formed during
      chlorination. On the other hand, bromate ion, a major ozonation DBP, was not a
      major contributor to the activity inducing chromosomal aberrations of the water
      treated with an ozone/chlorine sequential process. Therefore, ozonation is one
      possible option to reduce the health risk caused by DBPs even in the presence of
      bromide.

PMID- 15497865
TI  - Comparison of different advanced oxidation process to reduce toxicity and
      mineralisation of tannery wastewater.
AB  - Many organic compounds contained in wastewater are resistant to conventional
      chemical and/or biological treatment. Because of this reason different
      degradation techniques are studied as an alternative to biological and classical
      physico-chemical processes. Advanced Oxidation Processes (AOPs) probably have
      developed to become the best options in the near future. AOP while making use of
      different reaction systems, are all characterised by the same chemical feature:
      production of OH radicals (*OH). The versatility of AOPs is also enhanced by the
      fact that they offer different possibilities for OH radical production, thus
      allowing them to conform to specific treatment requirements. The main problem
      with AOPs is their high cost. The application of solar technologies to these
      processes could help to diminish that problem by reducing the energy consumption
      required for generating UV radiation. In this work, different AOPs (O3, TiO2/UV,
      Fenton and H2O2/UV) were examined to treat tannery wastewater or as a pre
      treatment step for improving the biodegradation of tannery wastewater, at
      different pH and dosage of the chemicals. Under certain circumstances retardation
      in biodegradation and/or an increase in toxicity may be observed within these
      treatment steps. Two different bioassays (Daphnia magna and Vibrio fischeri) have
      been used for testing the progress of toxicity during the treatment. In parallel
      other objectives were to analyse and identify organic compounds present in the
      untreated wastewater and arising degradation products in AOP treated wastewater
      samples. For this purpose substance specific techniques, e.g., gas chromatography
      mass spectrometry (GC-MS) in positive electron impact (El(+)) mode and
      atmospheric pressure ionisation (API) in combination with flow injection analysis
      (FIA) or liquid chromatography-mass and tandem mass spectrometry (LC-MS or LC-MS
      MS) were performed.

PMID- 15497866
TI  - Toxic effect of pharmaceuticals on methanogenesis.
AB  - Pharmaceuticals present in sewage may inhibit the biological processes in a
      sewage treatment plant. In this work, the toxic-effect of six pharmaceuticals
      (carbamazepine, sulfamethoxazole, propranolol hydrochloride, diclofenac sodium,
      ofloxacin and clofibric acid) on the anaerobic digestion process is assessed.
      Acetoclastic methanogenes are the most sensitive group of microorganisms
      participating in the anaerobic digestion process. Appropriate toxicity tests for
      these microorganisms were then based on assessing the impact of pharmaceuticals
      on the specific methanogenic activity (SMA) of the anaerobic biomass. The
      toxicity was expressed by the IC80 and IC50 values, i.e. the concentration at
      which bioactivity was 80% and 50% of the control, respectively. Results showed
      that the pharmaceuticals tested caused a mild inhibition to the methanogenes in
      most cases, related directly to the tendency of the compounds to adsorb on the
      anaerobic biomass.

PMID- 15497867
TI  - On the effect of pharmaceuticals on bacterial nitrite oxidation.
AB  - Pharmaceuticals or their metabolites are partially excreted with urine or faeces
      ending up in raw sewage. Many of these substances are not biodegradable and their
      presence in influents of municipal wastewater treatment plants may cause adverse
      effects to sensitive biological processes such as nitrification, while on the
      other hand, they may go through the activated sludge process unreacted. The
      second step of nitrification, i.e. oxidation of nitrite to nitrate is
      particularly sensitive. Inhibition of this step under uncontrolled conditions may
      lead to accumulation of nitrite nitrogen in the plant effluent, a form of
      nitrogen which is particularly toxic. The effects caused by the presence of seven
      different pharmaceuticals to a culture of nitrite-oxidizing bacteria isolated
      from activated sludge are presented. These pharmaceuticals were ofloxacin,
      propranolol, clofibrate, triclosan, carbamazepine, diclofenac and
      sulfamethoxazole. Different effects were observed for each of the pharmaceuticals
      tested in this study. In the cases of ofloxacin and sulfamethoxazole significant
      inhibition was observed. Triclosan presented a substantial inhibitory effect on
      the substrate (nitrite) reduction rate. The long-term effect of triclosan on
      nitrite oxidizers was also examined in a CSTR reactor and conclusions were drawn
      regarding the reversibility of the inhibition caused by this compound.

PMID- 15497868
TI  - Assessment of microbial natural attenuation in groundwater polluted with gasworks
      residues.
AB  - Intrinsic biodegradation, representing the key process in Natural Attenuation,
      was examined at a tar-oil polluted disposal site. Methods to assess microbial
      natural attenuation of BTEX and PAH included analysis of groundwater
      hydrochemistry, pollutant profiles, composition of the microflora, and microcosm
      studies. In the polluted groundwater downgradient the disposal site, oxygen and
      nitrate were only available adjacent to the groundwater table and at the plume
      fringes. In the anaerobic core of the plume, a sequence of predominating redox
      zones (methanogenic, sulphate-reducing, Fe(III)-reducing) was observed. Changing
      pollutant profiles in the plume indicated active biodegradation processes, e.g.
      biodegradation of toluene and naphthalene in the anaerobic zones. High numbers of
      microorganisms capable of growing under anaerobic conditions and of aerobic
      pollutant degrading organisms confirmed the impact of biodegradation at this
      site. In microcosm studies, the autochthonous microflora utilised toluene,
      ethylbenzene, and naphthalene under sulfate- and Fe(III)-reducing conditions.
      Additionally, benzene and phenanthrene were degraded in the presence of Fe(III).
      Under aerobic conditions, all BTEX and PAH were rapidly degraded. The microcosm
      studies in particular were suitable to examine the role of specific electron
      acceptors, and represented an important component of the multiple line of
      evidence concept to assess natural attenuation.

PMID- 15497869
TI  - LAS in urban rivers and factors contributing to reduction of their
      concentrations.
AB  - LC/MS analysis with improved SPE preparation was applied to determine trace
      amounts of LAS in river waters. By using this procedure, the distribution of LAS
      was investigated and compared with the previous concentration level measured by
      HPLC in the Akashi River flowing through urbanized coastal areas in Hyogo
      Prefecture, western Japan. Detected LAS were in the range of 0.6-11 microg/L and
      considerably lower than those in 1985. This indicated that LAS concentration
      levels reduced to 1/10 and below during the past 18 years. From the model
      analysis, major factors contributing to the reduction of their concentrations
      were estimated to be the sewerage development and the decrease of consumption of
      anionic surfactants. Statistical analysis of MBAS monitoring data suggested that
      over 90% of sewerage diffusion rate was needed in order to reduce LAS to the
      concentration level of the order of 10 microg/L in river waters.

PMID- 15497870
TI  - Re-evaluation and reconstruction of water purification system using soil. I.
      Assessment of soil as a sorbent of humic substances and phosphate ion.
AB  - The purpose of our study is to develop a treatment procedure for humic substances
      (HS hereafter) and phosphate ion in wastewater and environmental water by
      percolation of the water through a constructed soil layer at the hydraulic
      loading of a few metres per day. In the present work, batch sorption tests were
      conducted for more than 80 samples of soil, sludge, mineral and organic materials
      in order to find good sorbents for fulvic acid (FA hereafter) and phosphate ion.
      The results showed that the sorption of FA was high for some charcoal, and
      apatite and goethite minerals. Comparatively high sorption of FA was found for
      some Andosols and volcanic ash soil. Significant sorption of phosphate ion, on
      the other hand, was found for various types of soil, sludge from water treatment
      plants and some waste materials. The linear isotherm was obtained for the
      sorption of FA to a charcoal, apatite and goethite minerals, and Andosols.

PMID- 15497871
TI  - Re-evaluation and re-construction of water purification system using soil. II.
      Removal of pollutants from infiltrating water.
AB  - Presented in this paper are the results of a series of column experiments and a
      pilot scale test conducted to develop the treatment system of freshwater and
      wastewater by their percolation through soil and the other materials at the rate
      of a few metres per day. Materials that had high ability to sorb fulvic acid (FA
      hereafter) and phosphate ion were selected based on the results of the batch
      sorption tests and were processed into beads before subjecting them to the column
      test. The results of the column experiment suggested that the reagents added to
      increase the strength of the beads reduced the sorption of FA, thus causing the
      early breakthrough of the FA injected into the column. Less effect from the bead
      processing was observed for the removal of phosphate ion. Pilot scale test showed
      that the removal of particulate fraction of phosphorus differed among the
      materials used. The bead processing technique that can ensure the high water
      permeability while maintaining the sorption capacity of the material was required
      for further development of the treatment system.

PMID- 15497872
TI  - Teething problems highlight framework's lack of bite.

PMID- 15497873
TI  - Patient safety ideas. The safety gap.

PMID- 15497874
TI  - HSJ interview: Trevor Phillips. Diversity no charity case. Interview by Mary
      Louise Harding.

PMID- 15497875
TI  - Clinical management. Where medicine meets management. Teach to his own.
AB  - A course developed by an Isle of Wight diabetes consultant teaches patients to
      instruct other patients on self-management of the condition. Supporters say the
      training is more relevant to diabetes than the expert patient programme. Health
      professionals' wariness of the scheme has taken its toll on take-up of the
      service.

PMID- 15497876
TI  - Community services. Buried treasure.
AB  - Central Cornwall PCT suffers from a historical under-investment in community
      services. Fines related to delayed discharge will bring in pounds sterling 2m,
      which will help build up community capacity. A reorganisation of community
      hospitals is being planned.

PMID- 15497877
TI  - Finance. Playing for power.

PMID- 15497878
TI  - HSJ people. Where do they come in?

PMID- 15497879
TI  - My brilliant career--human resources director. Incredible journey.

PMID- 15497880
TI  - Racial diversity. Mountains to climb.

PMID- 15497881
TI  - [Without determining the current status there is no future].

PMID- 15497882
TI  - [Nursing pedagogues visit the "Workshop for Nurses": faculty in the "teaching
      plan" curriculum].

PMID- 15497883
TI  - [Qualification of faculties of nursing: future orientation instead of ideological
      brake].

PMID- 15497884
TI  - [Reforms in professional education in nursing: (no) way out of the special
      program?].

PMID- 15497885
TI  - [Significance of nutrition for coronary heart diseases: healthy eating--knowing
      how?].

PMID- 15497886
TI  - [Home nursing of a child with a heart defect: a bridge to the outside world].

PMID- 15497887
TI  - [Caring for patients with heart failure: promoting self-care capacity].

PMID- 15497888
TI  - [Presentation of statistical data in nursing 9--Scatter plots (II):
      Multidimensional evaluation].

PMID- 15497889
TI  - [Cardiovascular diseases from the viewpoint of public health: a mass social
      phenomenon].

PMID- 15497890
TI  - [Early defibrillation by laity: not a minute to waste].

PMID- 15497891
TI  - [Art therapy in heart diseases: access to feelings].

PMID- 15497892
TI  - [Spiritual dimensions of nursing--3: Life according to the Tora].

PMID- 15497893
TI  - [Internal quality development: a general practice concept].

PMID- 15497894
TI  - [With decision making model toward compromise: 4 questions for a solution].

PMID- 15497895
TI  - [Inpatient care--2: Ways for to restore investment costs].

PMID- 15497896
TI  - [When the heart weakens].

PMID- 15497897
TI  - [Foreign study with the Leonardo da Vinci Program: an "especially valuable"
      experience].

PMID- 15497898
TI  - [Developing and deepening of reflecting capacity of nurses--a research project
      exemplified by staff transitioning].

PMID- 15497899
TI  - Publishing the results of the estrogen-only arm of WHI.

PMID- 15497900
TI  - Do female sex hormones initiate breast cancer? A review of the evidence.
AB  - Over the past 2 years, the media have highlighted a number of epidemiological
      articles which suggest that estrogen therapy, with or without progestogens, is
      responsible for initiating breast cancer in postmenopausal women. However, the
      essential biological mutations necessary to induce a new breast cancer suggest
      that the increase in diagnosis is due to promotion of an already existing, but
      undiagnosed, oncogenic change, rather than to sex hormones initiating malignant
      mutations. In this review, anomalies in the hypothesis that hormonal therapy
      causes breast cancer are identified, the sequence of mutations which must occur
      prior to development of an invasive breast cancer are defined and the influence
      of the sex hormones on these changes is briefly reviewed. The conclusion is that
      sex hormones are mitogenic but not oncogenic.

PMID- 15497901
TI  - Human breast cell proliferation and its relationship to steroid receptor
      expression.
AB  - The steroidal regulation of proliferation and differentiation in the rodent
      mammary gland is well described, but how ovarian hormones regulate these
      processes in the human remains poorly understood. To investigate this, we
      developed the athymic nude mouse model in which intact normal human breast tissue
      is grafted subcutaneously and treated with estrogen and/or progesterone at human
      physiological serum levels. We demonstrated, first, that estrogen and not
      progesterone is the major epithelial cell mitogen in the adult non-pregnant, non
      lactating breast, second, that estrogen induces progesterone receptor (PR)
      expression and, third, that PR expression is maximally induced at low estrogen
      concentrations while a higher amount of estrogen was required to induce
      proliferation. These data raised the question of whether one cell type possessed
      differential responses to high and low estrogen concentrations or whether PR
      expression and proliferation occurred in two cell populations. Using double-label
      immunofluorescence, we demonstrated that steroid receptor expression and cell
      proliferation (Ki67 antigen) occurred in separate cell populations in normal
      human breast epithelium, and that cells expressing the estrogen receptor-alpha
      (ERalpha) invariably contained the PR. We also found that this dissociation
      between steroid receptor expression and cell proliferation in normal epithelium
      was disrupted at an early stage in breast tumor formation. Recent findings
      presented herein support the proposal that some ERalpha/PR-positive epithelial
      cells are quiescent breast stem cells that act as 'steroid hormone sensors'. Such
      hormone sensor cells are likely to secrete positive or negative
      paracrine/juxtacrine factors dependent on the prevailing estrogen or progesterone
      concentration to influence the proliferative activity of adjacent ERalpha/PR
      negative epithelial cells.

PMID- 15497902
TI  - Hormone therapy use after the Women's Health Initiative.
AB  - OBJECTIVE: To continue surveillance of hormone therapy (HT) use in an Australian
      population and to assess the impact of the Women's Health Initiative (WHI) and
      associated reports on HT use 16 months after the results of the WHI were first
      reported. METHODS: Data were obtained from the 2003 South Australian Health
      Omnibus Survey, which involves a representative, population face-to-face
      interview survey. Data were compared to five surveys undertaken between 1991 and
      2000, which had consistent methods and quality-control procedures. A total of 907
      interviews were conducted with women over 40 years in their own homes by trained
      health interviewers. RESULTS: In association with the timing of media reporting
      of the WHI, current HT use rates dropped from 28% in women over 50 years in 2000
      to an estimated 10.2% in 2002. By October 2003, current use rates had returned to
      18.8% in this age group. The media had been the main influence in the women's
      decision-making. Half of those who restarted therapy changed to another type of
      HT. Only 2.8% changed to an alternative/complementary therapy. CONCLUSIONS:
      Nearly two-thirds (64%) of those currently using HT in 2002 stopped therapy,
      mostly in response to the media reporting of the WHI. Nearly half of those who
      stopped HT in 2002 have since restarted. Media reporting greatly influences the
      use of hormonal therapies.

PMID- 15497903
TI  - Use and perception of hormone therapy following media reports of the Women's
      Health Initiative: a survey of Australian WISDOM participants.
AB  - OBJECTIVES: To investigate the impact of the Women's Health Initiative (WHI) on
      the use and perception of hormone therapy (HT) in well-informed and altruistic
      women who had volunteered for a similar long-term study of HT (Women's
      International Study of long Duration Oestrogen after Menopause, WISDOM). METHODS:
      A total of 840 South Australian WISDOM participants were sent questionnaires
      asking about their source of information about the WHI, interpretation of the
      2002 WHI findings, perception of HT as a risk factor for breast cancer, attitudes
      towards doctors and the media and intent to use HT in the future. RESULTS:
      Altogether, 618 participants (74%) responded. Written and verbal information
      provided by WISDOM were rated as the most helpful sources of information about
      the WHI. Participants were aware of the increase in breast cancer and decrease in
      fractures seen with combined estrogen/progestogen hormone therapy (EPT) but were
      less convinced about the other major findings, including cardiovascular disease
      and dementia. HT was rated as an important risk factor for breast cancer.
      Participants valued medical research and were more likely to question therapies
      without evidence. After WHI and WISDOM, most were willing to participate in a
      subsequent trial and most past HT users resumed therapy. CONCLUSIONS: There are
      sufficient recruits for future long-term HT studies if they are given sufficient
      quality information and individual counselling. Our study also suggests that
      women who are appropriately informed may choose to take long-term HT despite a
      more conservative approach advised by some agencies.

PMID- 15497904
TI  - A comparison of acupuncture and oral estradiol treatment of vasomotor symptoms in
      postmenopausal women.
AB  - OBJECTIVE: To compare the effects of electro-acupuncture with oral estradiol and
      superficial needle insertion on hot flushes in postmenopausal women. MATERIAL AND
      METHODS: Forty-five postmenopausal women with vasomotor symptoms were randomized
      to electro-acupuncture, superficial needle insertion or oral estradiol treatment
      during 12 weeks, with 6 months' follow-up. The number and severity of flushes
      were registered daily and the Kupperman index and a general estimate of
      climacteric symptoms were completed before, during and after therapy. RESULTS: In
      the electro-acupuncture group, the mean number of flushes/24 h decreased from 7.3
      to 3.5 (ANOVA, p < 0.001). Eleven of the 15 women had at least a 50% decrease in
      number of flushes (with a mean decrease of 82%). Superficial needle insertion
      decreased the number of flushes/24 h from 8.1 to 3.8 (p < 0.001). In seven out of
      13 women, the number of flushes decreased by at least 50% (mean decrease 83%). In
      the estrogen group, the number of flushes decreased from 8.4 to 0.8 (p < 0.001).
      The decrease in number of flushes persisted during the 24-week follow-up period
      in all treatment groups. The Kupperman index and the general climacteric symptom
      score decreased, and remained unchanged 24 weeks after treatment in all groups (p
      < 0.001). Electro-acupuncture decreased the number of flushes/24 h significantly
      over time, but not to the same extent as the estrogen treatment. No significant
      difference in effect was found between electro-acupuncture and the superficial
      needle insertion. CONCLUSION: We suggest that acupuncture is a viable alternative
      treatment of vasomotor symptoms in postmenopausal women and cannot recommend
      superficial needle insertion as an inactive control treatment.

PMID- 15497905
TI  - Menopause in Australia and Japan: effects of country of residence on menopausal
      status and menopausal symptoms.
AB  - OBJECTIVES: The aim of the study was to explore the effects of country of
      residence on menopausal status and menopausal symptoms in Australian and Japanese
      women. The study objectives included exploring the impact of country of residence
      (Australia and Japan) and menopausal status on menopausal symptoms, and
      identifying whether country of residence (Australia and Japan) moderates the
      relationship between menopausal status and menopausal symptoms. METHODS: Analyses
      are based on 1743 women aged between 40 and 60 years who participated in the
      multi-race, multi-site, cross-sectional study of mid-aged women called the
      Australian and Japanese Midlife Women's Health Study (AJMWHS) in 2001--2002.
      Study participants completed a mailed questionnaire that contained questions on a
      variety of health-related topics. RESULTS: In both cultures there was a similar
      increase in prevalence of depression (p < 0.001), somatic symptoms (p < 0.001)
      and vasomotor symptoms (p < 0.001) at perimenopause. Australian women experienced
      more night sweats than Japanese women but the prevalence of hot flashes was not
      statistically different. Postmenopausal Japanese women had more somatic,
      psychological and sexual symptoms. The main effect for menopausal status and the
      interaction effect of country of residence was significant in the somatic
      symptoms (p < 0.001), but not in any of the other areas. CONCLUSIONS: Vasomotor,
      psychological and somatic symptoms decrease after menopause in Australian women,
      with only sexual symptoms continuing. In Japanese women, somatic, psychological
      and sexual symptoms remain high after menopause. It is possible that
      westernization may be having a significant impact on the aging of women in Japan
      and it is, therefore important to capture through research just what this impact
      may be.

PMID- 15497906
TI  - How menopause affects the lives of women in suburban Chandigarh, India.
AB  - OBJECTIVE: To ascertain the effect of menopause on the lives of women in suburban
      Chandigarh. METHOD: An integrated qualitative and quantitative study was
      performed in a low socioeconomic area of Chandigarh city, India. Women aged 40-60
      years were enlisted and interviewed. RESULTS: Of the 725 enlisted women, 298
      (41%) had attained menopause, 47 (6.5%) were in transition and 43 (5.9%) had
      undergone hysterectomy. The transition phase lasted for 1-12 months in 48.7% of
      cases and for 1 year or more in 20.8% of cases. No transitional changes were
      reported by 30.5% of women. A change in menstrual pattern was the hallmark of
      this phase and included delayed periods (37.6%), heavy bleeding (13%), scanty
      periods (7%) or a mixed pattern (11.7%). The majority of women interviewed (76%)
      did not experience any tension on attainment of menopause. Diminished acuity of
      vision was the most commonly reported menopausal symptom. Hot flushes were
      reported by 17.1% of women. Most women (94%) welcomed menopause. Use of hormone
      replacement therapy was not reported by anyone. CONCLUSION: Although north Indian
      women experienced various symptoms at menopause, they largely ignored these,
      while welcoming the freedom from menstruation-related worries.

PMID- 15497907
TI  - Low levels of endogenous estradiol protect bone mineral density in young
      postmenopausal women.
AB  - OBJECTIVE: Low levels of endogenous estrogens may play a role in the protection
      of bone mineral density (BMD) in healthy postmenopausal women. The aim of this
      study was to evaluate the effect of endogenous estradiol and testosterone on bone
      mass in young and older healthy postmenopausal women. METHODS: The study involved
      99 postmenopausal women aged 55-75 years. The BMDs of the lumbar spine, proximal
      femur and total skeleton were determined. Measurements were taken of serum
      calcium, bone alkaline phosphatase, Crosslaps, estradiol, estrone, sex hormone
      binding globulin, testosterone, bioavailable testosterone and urine calcium.
      Estradiol was measured using a sensitive assay with a lower detection limit at 5
      pg/ml. RESULTS: A multivariate analysis showed that the BMD of the lumbar spine
      was significantly predicted by estradiol (p < 0.05), and testosterone (p <
      0.0001). Likewise, testosterone was found to be an independent predictor of the
      BMD of the total femur (p < 0.001) and the total skeleton (p < 0.001). The
      population was divided into two groups: < or = 65 (Group 1) and > 65 years (Group
      2) of age and also stratified according to estradiol levels: > 10 and < or = 10
      pg/ml. Significant differences in BMD were found in women in Group 1 in whom
      estradiol levels higher than 10 pg/ml were associated with a higher BMD of the
      lumbar spine (+ 14%, p < 0.01), proximal femur (+ 6%, p < 0.05) and total
      skeleton (+ 7%, p < 0.05) compared with women with estradiol levels below 10
      pg/ml. Bone alkaline phosphatase levels (p < 0.05) and serum Crosslaps (not
      significant) were lower in women in Group 1 with a level of estradiol more than
      10 pg/ ml. CONCLUSION: Endogenous estradiol levels higher than 10 pg/ml and
      testosterone protected bone mass in healthy postmenopausal women under 65 years
      of age. These results were not observed in the group of older women.

PMID- 15497908
TI  - Estradiol and drospirenone for climacteric symptoms in postmenopausal women: a
      double-blind, randomized, placebo-controlled study of the safety and efficacy of
      three dose regimens.
AB  - METHOD: A randomized, placebo-controlled trial was conducted to evaluate the
      safety and efficacy of drospirenone (1, 2 or 3 mg) combined with estradiol (1 mg)
      in the treatment of climacteric symptoms in healthy postmenopausal women.
      RESULTS: The frequency of hot flushes was significantly decreased in all
      treatment groups (range 86-90%) in comparison to placebo (45%, p < or = 0.001)
      and remained suppressed at 16 weeks. Treatment with drospirenone and estradiol
      also decreased the intensity and severity of sweating, sleep problems,
      depression, nervousness, and urogenital symptoms. Most adverse events were mild
      or moderate, with similar rates observed in all groups. No serious adverse events
      or clinically significant laboratory abnormalities attributed to treatment
      occurred. CONCLUSION: These results demonstrate that the combinations of 1, 2,
      and 3 mg drospirenone with 1 mg estradiol are safe and effective for the
      treatment of climacteric symptoms.

PMID- 15497909
TI  - Clinical background of women prescribed tibolone or combined estrogen +
      progestogen therapies: a UK MediPlus study.
AB  - OBJECTIVES: To describe and compare the history and clinical characteristics of
      women who were prescribed tibolone or one of the following combined estrogen +
      progestogen therapies (CEPT): sequential conjugated equine estrogens
      (CEE)/norgestrel, sequential CEE/medroxyprogesterone acetate (MPA), continuous
      CEE/MPA or continuous estradiol/norethisterone acetate (NETA). METHODS: This was
      a descriptive study using MediPlus, a UK Primary Care database; 3762 women
      participated who, between July 1st, 1999 and June 30th, 2001, were prescribed
      either tibolone or one of the CEPT regimens mentioned above. Risk factors
      associated with endometrial cancer and breast cancer were assessed. RESULTS: The
      results of this study suggest that the clinical background of women who were
      prescribed tibolone differed from that of the women who were prescribed the
      combination products. More frequently than expected women who were most recently
      prescribed tibolone have a history of chronic breast disease, a personal history
      of breast cancer or a history of being prescribed (long-term) estrogen-only
      therapy. Furthermore, this group of women more frequently had hypertension and
      performed uterine procedures recorded in their medical records. This preferential
      prescribing of tibolone occurs at first-ever prescription of hormone therapy but
      is, in some instances, the underlying reason for switch behavior. CONCLUSION: In
      the UK, general practitioners seem to preferentially prescribe tibolone to women
      with an increased risk for breast and endometrial cancer, as compared to women
      being prescribed other CEPT products.

PMID- 15497910
TI  - Practical recommendations for hormone replacement therapy in the peri- and
      postmenopause.

PMID- 15497911
TI  - Introduction to the special issue on psychosocial perspectives on amputation and
      prosthetics.

PMID- 15497912
TI  - Amputation rehabilitation and prosthetic restoration. From surgery to community
      reintegration.
AB  - PURPOSE: The purpose of this review is to summarize the literature related to the
      advances that have taken place in the management and rehabilitation care of limb
      amputation. RESULTS: Prostheses for the lower and upper limb amputee have changed
      greatly over the past several years, with advances in components, socket
      fabrication and fitting techniques, suspension systems and sources of power and
      electronic controls. Higher levels of limb amputation can now be fitted with
      functional prostheses, which allow more patients to achieve independent life
      styles. This is of particular importance for the multi-limb amputee. The
      rehabilitation of more traditional lower limb levels of amputation have also
      greatly benefited from the technological advances including energy storing feet,
      electronic control hydraulic knees, ankle rotators and shock absorbers to mention
      a few. For the upper limb amputee, myoelectric and proportional controlled
      terminal devices and elbow joints are now used routinely in some rehabilitation
      facilities. Experimental prosthetic fitting techniques and devices such as the
      use of osseo-implantation for suspension of the prosthesis, tension control hands
      or electromagnetic fluids for knee movement control will also be briefly
      discussed in this paper. CONCLUSION: It is possible to conclude from this review
      that many advances have occurred that have greatly impacted the functional
      outcomes of patients with limb amputation.

PMID- 15497913
TI  - Psychosocial adjustment to lower-limb amputation: a review.
AB  - PURPOSE: To review the existing literature on the social and psychological
      challenges faced by people with an amputation and to provide a detailed analysis
      of the literature examining psychological adjustment to these challenges across
      time. METHOD: Existing papers on psychological adjustment to amputation were
      analysed according to their results, methodology, and conclusions. RESULTS:
      Although depression and anxiety are relatively high up to 2 years post
      amputation, they appear to decline thereafter to general population norms.
      However, social discomfort and body-image anxiety have also been found among some
      people with amputations, and these have been associated with increased activity
      restriction, depression, and anxiety. Factors associated with positive adjustment
      to limb loss include greater time since amputation, more social support, greater
      satisfaction with the prosthesis, active coping attempts, an optimistic
      personality disposition, a lower level of amputation in the case of lower limbs,
      and lower levels of phantom limb pain and stump pain. CONCLUSION: The majority of
      studies on adjustment to amputation are cross-sectional in design and have used
      noncomparable measures. Furthermore, they have neglected to study many important
      areas of rehabilitation, including immediate reaction to amputation, adjustment
      during and shortly after the rehabilitation period, and development of a changed
      sense of self and identity. In order to address these concerns, more longitudinal
      and qualitative research is called for. We end by outlining the components of a
      descriptive phased model of the rehabilitation process.

PMID- 15497914
TI  - Coping after trans-femoral amputation due to trauma or tumour--a phenomenological
      approach.
AB  - PURPOSE: To describe, by use of a phenomenological approach, how relatively young
      trans-femoral amputees experienced their amputation and their coping strategies
      in the acute phase and over time. METHOD: Eleven trans-femoral amputees, median
      age 33.5 years, were interviewed. The amputation was caused by tumour, motorcycle
      accidents or work-related traumas. Amputation was made in median 7.5 years before
      the interview. The informants were community dwelling and managed well indoors.
      One had a half disablement pension and all the others were working or studying
      full time. The interviews were tape-recorded and transcribed verbatim. RESULTS:
      Two themes emerged. In the first theme 'Experiences of the amputation' denial and
      avoidance were the coping strategies mainly used. In the second theme 'Coping
      strategies to relate to a new norm' the informants used downward comparison,
      positive comparison and repression. Only one informant indicated a full
      acceptance of his situation. CONCLUSION: Relatively young, trans-femoral amputees
      within this sample, have not reached the acceptance level, though a long time has
      passed since the amputation. They might have benefited from professional support
      and guidance during the rehabilitation process in order to improve coping
      strategies to relate to a new norm.

PMID- 15497915
TI  - A two-year longitudinal study of social support following amputation.
AB  - PURPOSE: (1) To describe one aspect of social support, social integration,
      longitudinally for 2 years following lower limb amputation and (2) to explore the
      impact of social support on depression, pain interference, life satisfaction,
      mobility, and occupational functioning. METHOD: Eighty-nine adults recruited from
      consecutive admissions to an orthopaedic surgery service completed telephone
      interviews 1, 6, 12 and 24 months following amputation surgery. Dependent
      variables included the Social Integration (SI) sub-scale of the Craig Handicap
      Assessment and Reporting Technique (CHART) and the Multidimensional Scale of
      Perceived Social Support (MSPSS). RESULTS: There was a high level of SI among
      most persons following lower limb amputations that was relatively unchanged in
      the 2 years following surgery. However, mean levels of SI were lower in this
      group compared to a sample without disabilities. MSPSS scores were highly
      variable, ranging from almost no support to the maximum amount of support. MSPSS
      was an important concurrent predictor of pain interference, life satisfaction,
      and mobility, controlling for demographic and amputation-related factors.
      Baseline MSPSS predicted mobility and occupational functioning 6 months post
      amputation, controlling for demographic and amputation-related factors.
      CONCLUSIONS: Findings suggest that interventions aimed at improving the quality
      of social relationships after amputation may facilitate participation in
      activities.

PMID- 15497916
TI  - A prospective study examining balance confidence among individuals with lower
      limb amputation.
AB  - PURPOSE: In this study we assessed whether balance confidence scores changed over
      a 2-year follow up period, and identified predictors of balance confidence and
      predictors of change in balance confidence among lower limb amputees. METHOD: A
      prospective follow-up survey of 245 community living adults with unilateral below
      and above knee lower limb amputation who used their prosthetic limb daily was
      conducted. Balance confidence, assessed using the 16-item Activity-specific
      Balance Confidence (ABC) Scale, socio-demographic, health and amputation related
      variables were collected at baseline and 2 years later. RESULTS: ABC scores were
      similar at baseline (mean = 67.6; SD = 25.7) and follow up (mean = 68.0; SD =
      25.8). Lower balance confidence scores at follow up were predicted by older age,
      being female, use of a mobility device, poor perceived health, increased symptoms
      of depression, having to concentrate while walking, and fear of falling (all p <
      0.05). Predictors of change in balance confidence included gender and perceived
      health (all p < 0.05). CONCLUSION: Balance confidence appears to be a persistent
      problem in the amputee population. Health professionals are encouraged to
      consider balance confidence as a potentially important variable that may
      influence function in this clinically unique group of individuals. The identified
      predictor variables may be useful to clinicians in targeting individuals who
      require attention to improve balance confidence.

PMID- 15497917
TI  - Psychosocial predictors of long-term adjustment to lower-limb amputation and
      phantom limb pain.
AB  - PURPOSE: To evaluate the utility of a biopsychosocial model to predict long-term
      adjustment to lower-limb amputation and phantom limb pain (PLP). METHOD: One
      month after lower-limb amputation, 70 participants completed measures of PLP
      intensity, cognitions (catastrophizing, perceived control over pain), coping
      (pain-contingent rest), social environment (social support, solicitous
      responding), and functioning (pain interference, depressive symptoms). The
      measures of functioning were administered again at 1- and 2-years post
      amputation. Multiple regression analyses were used to examine the ability of the
      psychosocial variables at 1-month post-amputation to predict changes in the
      functioning measures over time. RESULTS: The psychosocial variables at 1-month
      post-amputation, controlling for initial PLP intensity, accounted for 21% of the
      variance in change in depressive symptoms at 1-year (p < 0.05), and 27% and 22%
      (p's < 0.01 and 0.05, respectively) of the variance in change in pain
      interference and depressive symptoms, respectively, at 2-years post-amputation.
      Catastrophizing and social support were associated with decreases (improvement)
      in both criterion measures, while solicitous responding was associated with
      increases (worsening) in both measures. DISCUSSION: The findings support a
      biopsychosocial model of long-term adjustment to amputation and PLP. In addition,
      results suggest that some psychosocial variables are more important than others
      for predicting adjustment, providing important implications for early
      interventions after amputation.

PMID- 15497918
TI  - The illusive phantom: does primary care meet patient need following limb loss?
AB  - PURPOSE: Anecdotal evidence suggests that General Practitioners (GPs) vary in
      their understanding of phantom pain and associated factors in amputees. This has
      implications in that the GP's conception of the problem will determine what
      treatment or referral is offered. METHOD: The present study aimed to explore GP's
      knowledge and understanding of phantom limb pain using a postal questionnaire. A
      sample of 129 GPs responded resulting in a response rate of 38%. RESULTS: The
      results suggest that GPs underestimate the prevalence, intensity and duration of
      phantom and residual limb pain. Moreover, inconsistencies in the reasons given
      for referral to specialist services for the management of phantom pain were
      reported. CONCLUSION: These findings have serious implications for the management
      of phantom limb pain, disability and psychological distress in amputees in that
      GPs not only provide first line treatment, but are also the gatekeepers for
      referral to other services. Given this, the role of other professionals within
      the primary health care team may prove an additional resource for providing both
      support and accurate information to amputees in the community.

PMID- 15497919
TI  - Mirror treatment of lower limb phantom pain: a case study.
AB  - PURPOSE: Phantom limb pain (PLP) can be an enduring and distressing experience
      for people with amputations. Previous research has shown that 'mirror treatment'
      can reduce PLP for some people who have an upper limb amputation, and that it can
      increase a sense of motor control over the phantom in people with lower limb
      amputations who are not reporting PLP. There has been no previous report of
      therapeutic 'mirror treatment' for lower-limb phantom pain. METHOD: We present
      the first case study of the use of 'mirror treatment' in a person with a lower
      limb amputation who was reporting PLP at the time of treatment. RESULTS: During
      the intervention there was a significant reduction in his PLP, an increase in
      sense of motor control over the phantom and a change in aspects of the phantom
      limb that was experienced. CONCLUSION: This case study, conducted in a
      conventional clinical setting, supports the potential of 'mirror treatment' for
      PLP in people with a lower limb amputation.

PMID- 15497920
TI  - Phantom pain: a sensitivity analysis.
AB  - PURPOSE: To analyse how decisions to dichotomise the frequency and impediment of
      phantom pain into absent and present influence the outcome of studies by
      performing a sensitivity analysis on an existing database. METHOD: Five hundred
      and thirty-six subjects were recruited from the database of an orthopaedic
      workshop and filled out a questionnaire in which the following items were
      assessed: demographics, side, date, level and reason of amputation, presence and
      frequency of phantom sensations, phantom pain and stump pain, and impediment due
      to phantom pain. RESULTS: The prevalence of phantom pain ranged from 7-72% when
      different cut off points for the frequency of phantom pain were applied. The
      significance of the various risk factors for the prevalence of phantom pain
      changed when different cut off points were applied. Only stump pain and phantom
      sensations were significant risk factors for all cut off points. Risk factors for
      the impediment of phantom pain changed when different cut off points were applied
      and these risk factors were different from those for the prevalence of phantom
      pain. CONCLUSION: The choice of cut off points influences the outcome of phantom
      pain studies considerably. This study provides some insight into the differences
      in prevalence and risk factors found in literature.

PMID- 15497921
TI  - Comparison of clinical test and questionnaires for the evaluation of upper limb
      prosthetic use in children.
AB  - PURPOSE: The aim of the present study was to find out if there was a correlation
      between an observational clinical test and a questionnaire for the evaluation of
      upper limb prosthetic use in children and to determine which one was better and
      easier to use in clinical practice. METHOD: Twenty children who were patients of
      the children's prosthetic clinic at the Rehabilitation Institute in Ljubljana,
      Slovenia, and had a functional prosthesis were included in the study. The age
      appropriate subtest of the University of New Brunswick Test of Prosthetic
      Function (the UNB test) was assessed by an occupational therapist. Parents
      completed either the Child Amputee Prosthetics Project-Functional Status
      Inventory for Preschool children (CAPP-FSIP) or the Child Amputee Prosthetics
      Project-Functional Status Inventory (CAPP-FSI), depending on which was
      appropriate for the child's age. Information was limited to the upper extremity
      items. RESULTS: We found a significant correlation between UNB spontaneity and
      skill score (r = 0.956, p = 0.000) and also between the parental CAPP score and
      UNB test (UNB spontaneity--CAPP activities r = 0.634, p = 0.003; UNB spontaneity-
      CAPP prosthetic use r = 0.542, p = 0.014, UNB skill--CAPP activities r = 0.559, p
      = 0.010, UNB skill--CAPP prosthetic use r = 0.597, p = 0.005). CONCLUSIONS: We
      concluded that both instruments can be used for assessing upper limb prosthetic
      use in children but neither is an optimal choice.

PMID- 15497922
TI  - A comparison of upper limb amputees and patients with upper limb injuries using
      the Disability of the Arm, Shoulder and Hand (DASH).
AB  - PURPOSE: To use the Disability of the Arm Shoulder and Hand (DASH) scale to
      measure the disability of patients with upper limb amputation(s) and to compare
      these to other upper limb injuries. METHOD: All 274 patients over the age of 18
      years presenting to Prince Henry Hospital in Sydney over a 4-year time frame were
      given the DASH assessment tool and asked to complete it under supervision of the
      Occupational Therapist. RESULTS: Patients with brachial plexus injuries, Complex
      Regional Pain Syndrome and bilateral upper limb amputations demonstrated
      significantly higher levels of disability to patients with unilateral upper limb
      amputations. Partial hand amputees reported a higher level of disability than
      major unilateral upper limb amputees. For the 48 patients who completed pre- and
      post-treatment assessments, there was a significant improvement in their health
      status. CONCLUSIONS: Further research is required to understand the factors that
      affect a patient's perceptions of their disability. Perhaps the definitive nature
      of an amputation and the immediate involvement of highly skilled health
      professionals serve to assist patients to accept their injury and therefore
      minimizes the level of disability.

PMID- 15497923
TI  - Using the theory of planned behaviour to develop an assessment of attitudes and
      beliefs towards prosthetic use in amputees.
AB  - PURPOSE: To develop a questionnaire based on the theory of planned behaviour
      (TPB) to predict prosthetic use. METHOD: In part one, 31 amputees over 50 years
      of age with peripheral arterial disease completed attitude items containing 27
      bipolar adjectives and open-ended questions on behavioural, normative and control
      beliefs relating to using the prosthesis. Academic, clinical and patient experts
      (n = 12) identified bipolar adjectives with best face validity. In part two, 15
      amputees completed three behavioural format questions relating to prosthetic use
      and were asked to indicate the easiest to answer. RESULTS: Following the
      completion of the attitude items by the amputees and the expert panel review, 5
      items remained (Cronbach's alpha = 0.87) with corrected item-total correlations
      ranging from 0.43 to 0.83. Modal behavioural beliefs concerned mobility (46.5%),
      independence (25.6%) and participation restrictions (16.3%), normative beliefs
      concerned family (33.3%), NHS staff (31.7%), friends (19.1%) and other patients
      (15.9%) and control beliefs concerned stairs (21.1%), slippery/rough surfaces
      (28.9%), disabled facilities (54.8%) and people helping (22.6%). In relation to
      part 2, an exact numerical report of hours and days of prosthetic use was found
      easiest to answer (73%). CONCLUSIONS: Based on this qualitative and quantitative
      development work, the questionnaire contains five attitude items, six
      behavioural, eight normative, eight control belief items and two self-report
      questions of the behaviour.

PMID- 15497924
TI  - Psychological factors after traumatic amputation in landmine survivors: the
      bridge between physical healing and full recovery.
AB  - PURPOSE: Limb loss due to a landmine injury is sudden and devastating. The
      resulting disability makes life challenging in a world where physical ability is
      the 'norm'. In order to better understand the psychological adjustments
      individuals make in their recovery from a landmine injury, the Landmine Survivors
      Network conducted an exploratory qualitative study to determine factors that
      contribute to an individual's recovery. The study examined psychosocial aspects,
      coping strategies, and resilience characteristics of limb loss survivors across
      differing cultural, societal and economic backgrounds. METHOD: Eighty-five
      participants (68 persons of limb loss, 10 family members, seven service
      providers) were interviewed using a semi-structured protocol in the USA and an
      open-ended format in six landmine affected countries. Data analysis was completed
      using grounded theory analytic strategies. RESULTS: Data indicated that the
      survivors' acceptance of limb loss and their state of psychological recovery were
      greatly influenced by the individual's resilience characteristics, social
      support, medical care, economic situation and societal attitudes toward people
      with disabilities. CONCLUSION: Recovery from traumatic amputation in landmine
      survivors needs to be comprehensive and coordinated, and requires addressing the
      individual's physical, psychological, economic and social needs within the
      context of family, community, and the socio-cultural environment in which they
      live.

PMID- 15497925
TI  - Sexuality in persons with limb amputation: a meaningful discussion of re
      integration.
AB  - PURPOSE: Rehabilitation professionals do not appear to be sufficiently prepared
      to deal with the sexual issues of people with a physical disability, although
      they have recognized the value of discussing them during the rehabilitation
      process. This commentary argues that the sexuality of people with a disability
      should be evaluated from the two viewpoints of sexual function and sexual
      concern. With regard to people with a limb amputation, their sexual life has not
      attracted researchers' or clinicians' interest because their sexual function is
      usually preserved, is the same as that of able-bodied persons, and there is a
      perception that assistance is not required. Indeed, the number of published
      studies on the sexuality of this population is apparently fewer than the number
      of studies on the sexuality of persons with central nervous system impairment.
      CONCLUSION: Investigation of the body image of people with a limb amputation and
      recognition of their needs are considered to be necessary for further discussion
      of this theme. Discussion of sexuality with some realistic statistical figures
      should also have great value in assisting with the re-integration of people with
      a limb amputation.

PMID- 15497926
TI  - Diversity in adjustment to a leg amputation: case illustrations of common themes.
AB  - PURPOSE: To provide in-depth case descriptions that illustrate the common themes
      in the research literature on psychological adjustment to a lower-extremity
      amputation as well as capture the uniqueness of each individual's response to
      this prevalent acquired disability. METHOD: Four cases were chosen based on the
      diversity of adjustment issues they represented. These case presentations were
      reconstructed from evaluations completed by the authors, all psychologists, as
      part of routine care on an inpatient rehabilitation service. Identifying
      information was changed to protect confidentiality. CONCLUSIONS: Taken together,
      these four cases serve to underscore the importance attending to common issues
      such as post-amputation depression and anxiety, body image, feelings of
      vulnerability, social support changes, grief, pre-amputation psychological issues
      and phantom limb pain and sensations. Psychological assessment and referrals for
      treatment should be included as part of the routine care provided to individuals
      with amputations, irrespective of the length of time that has passed since the
      amputation.

PMID- 15497927
TI  - Real time RT-PCR analysis of thyroglobulin mRNA in peripheral blood in patients
      with congenital athyreosis and with differentiated thyroid carcinoma after
      stimulation with recombinant human thyrotropin.
AB  - OBJECTIVE: Thyroglobulin (Tg), measured by immunometric assay, is the most
      sensitive and widely used clinical marker for thyroid cancer progression and
      relapse. However, these Tg determinations are of limited sensitivity and
      susceptible to interference by Tg autoantibodies. As a possible diagnostic
      alternative, we tested a real time RT-PCR protocol to determine Tg mRNA levels in
      peripheral blood. METHODS: Tg mRNA was determined by real-time RT-PCR using total
      RNA from peripheral blood. Tg mRNA blood levels were calibrated to the mRNA
      encoding the housekeeping enzyme glyceraldehyde phosphate dehydrogenase (GAPDH);
      pooled blood from ten healthy subjects served as a RT-PCR positive control.
      RESULTS: Tg mRNA and serum Tg were detected in twelve patients with
      differentiated thyroid cancer (DTC) after thyroidectomy and radioiodine therapy,
      however, there was no correlation with the clinical stage. An increase in Tg mRNA
      and protein was observed after application of recombinant human thyrotropin
      (rhTSH) in four patients with DTC stimulated with rhTSH for postoperative follow
      up. Tg mRNA and protein were also detected in four congenital athyreotic
      patients. Analysis of Tg mRNA levels using a commercial multiple tissue Northern
      blot revealed Tg hybridization signals in several extrathyroidal tissues
      (salivary gland, trachea, kidney, pancreas, adrenal gland, etc.). CONCLUSIONS:
      Our data suggests that RT-PCR detects Tg mRNA of extrathyroidal origin, from
      leukocytes or from metastasizing carcinoma cells under basal conditions or after
      TSH stimulation. However, considering the marked and highly variable individual
      Tg mRNA backgrounds, interpretation of real time PCR results requires caution.
      This limits the clinical use of Tg mRNA determination by real time PCR to an
      individual tumor progression marker in follow-up.

PMID- 15497928
TI  - In vitro effects of inhibin on apoptosis and apoptosis related proteins in human
      ovarian granulosa cells.
AB  - OBJECTIVE: To clarify the in vitro effects of inhibin A (I) on apoptotic cell
      death and its mechanisms in ovarian granulosa cells the immunoexpression patterns
      of the apoptosis markers caspase-3 and pro- and anti-apoptotic proteins (Bcl-2,
      Bcl-xl, Bak) were evaluated in ovarian granulosa cells collected from women with
      different hormonal status. MATERIALS AND METHODS: Granulosa cells were isolated
      from follicles of women participating in an in vitro fertilization (IVF) program,
      normally cyclic (NC) and premenopausal women (PrM). The obtained cells were
      cultured for 72 h with inhibin A (Sigma, USA)--10 ng/ml. The concentration of
      estradiol in the culture medium was determined by radioimmunoassay using the Coat
      A-Count kit (Nippon, Japan), whose intra- and interassay coefficients of
      variations were 6,8% and 6,2% respectively. The expression of caspase-3, Bak, Bcl
      2, Bcl-xl was investigated immunohistochemically. The percentages of
      immunopositive cells were calculated and Student's t-test was used for
      statistical analysis. RESULTS: Addition of inhibin A (10 ng/ml) to granulosa
      cells cultures resulted in increased estradiol production. Maximal stimulation
      was observed in granulosa cells collected from women participating in IVF whereas
      minimal effect of inhibin treatment on estradiol production was demonstrated in
      premenopausal women. Inhibin A exposition enhanced the immunoexpression of
      prooncogenes (Bcl-2, Bcl-xl) and reduced the expression of caspase-3 and pro
      apoptotic protein Bak in ovarian granulosa cells from the three experimental
      groups. CONCLUSIONS: Our findings suggest that inhibin A in vitro stimulates the
      estradiol secretion by granulosa cells dependently of the woman hormonal status,
      while it inhibits apoptotic process in granulosa cells independently of the
      hormonal status.

PMID- 15497929
TI  - Concentration of metalloproteinase-2 and tissue inhibitor of metalloproteinase-2
      in the serum of patients with benign and malignant thyroid tumours treated
      surgically.
AB  - OBJECTIVES: Neoplastic angiogenesis is an essential stage of growth, progression
      and invasion of solid tumours. The process of basement membrane degradation and
      remodelling of the extracellular matrix (EMC) involves proteolytic enzymes called
      metalloproteinases. Among the numerous proteolytic enzymes of this group the key
      role is played by metalloproteinase-2 (MMP-2) and tissue inhibitor of
      metalloproteinase 2 (TIMP-2). Tissue expression and concentration of these
      compounds in body fluids have been used in early diagnostics of tumours
      development, assessment of tumours advancement and treatment results monitoring.
      The aim of the study was to evaluate the concentration of MMP-2 and TIMP-2 in
      blood serum of patients with benign and malignant thyroid tumours and the effect
      of surgical treatment on these parameters in the postoperative period as well as
      assessment whether to MMP-2 and TIMP-2 serum concentration in patients with
      thyroid cancer positively correlates with the clinical staging classification of
      the International Union Against Cancer (UICC). PATIENTS AND METHODS: The study
      group consisted of 53 patients with various types of thyroid cancer and 23
      patients with benign thyroid tumours, while 26 healthy adults served as controls.
      According to clinical staging classification of thyroid cancer the 32 patients
      were classified with stage I, 6 with stage II, 8 with stage III and 7 with stage
      IV. We have found higher mean concentration of MMP-2 in 53 patients with thyroid
      cancer as compared to the control group and the group of 23 patients with benign
      thyroid tumours. All patients were treated operatively. Additionally, a
      significant effect of radical surgical treatment on mean concentration of MMP-2
      and TIMP-2 in patients with papillary and follicular thyroid cancer was
      demonstrated. CONCLUSIONS: MMP-2 and its tissue inhibitor TIMP-2 apparently play
      a significant role in the pathogenesis of thyroid cancer. Evaluation of their
      concentration in peripheral blood serum may be useful for the differentiation
      between benign and malignant thyroid tumours. Serum MMP-2 and TIMP-2
      concentrations in patients with thyroid cancer did not significantly correlate
      with the clinical staging of thyroid cancer.

PMID- 15497930
TI  - Hormonal control of protein glycosylation: role of steroids and related
      lipophilic ligands.
AB  - Glycosylation represents one of the most frequent and certainly the most variable
      co- and post-translational modification of proteins. Carbohydrate moieties of
      glycoproteins are known to provide important prerequisites for various biological
      functions, and their structural diversity can serve as ideal candidate to carry
      also biological information. Production and/or function of various glycoproteins
      is under control of steroids and other ligands of nuclear receptors which
      influence synthesis, glycosylation, storage or usage of target proteins. It
      appears that among small lipophilic hormonal compounds the steroids are chiefly
      involved in regulation of protein glycosylation. There is no apparent difference
      between ability of these hormones to regulate N- or O-glycosylation, but majority
      of documented cases deals with terminal modifications involving sialylation or
      fucosylation of N-linked carbohydrate moieties. In spite of the knowledge on
      glycosylation in general, published results offers only a glimpse of data on the
      hormonal control of glycosidase activity which is equally required for
      carbohydrate chain elongation as is the activity of various glycosyltransferases.
      The significance of this research is daily growing owing to the fact that changes
      in glycosylation pattern of various intracellular or secretory proteins not only
      reflect developmental or differentiation stage but also serve as well established
      markers in invasiveness or regression of numerous cancers responding to hormonal
      stimuli. Combination of classical methods and more complex approach in
      genetically well defined model systems can not only increase recent surge of
      interest in glycosylation but also provide a formidable amount of qualitatively
      new type of data on the mechanism how hormones control glycosyltransferases and
      glycosidases and how their activity is interconnected to the synthesis of
      substrates, posttranslational maturation, and final destination or function of
      target proteins.

PMID- 15497931
TI  - Endocrine and metabolic activities of a recently isolated peptide hormone
      ghrelin, an endogenous ligand of the growth hormone secretagogue receptor.
AB  - Ghrelin is a member of the group of growth hormone secretagogues (GHSs). It is a
      peptide hormone, recently isolated from stomach as an endogenous ligand for the
      growth hormone secretagogue receptor (GHS-R). Ghrelin is mostly produced by the
      stomach, although its production has been proved in various tissues. It is a
      potent releaser of growth hormone (GH) from anterior pituitary cells, but it also
      stimulates the release of other hypophyseal hormones. Ghrelin stimulates food
      intake and induces metabolic changes leading to an increase in body weight and
      body fat mass. This effect seems to be independent of GH action and needs an
      intact NPY/AGRP (neuropeptide Y/agouti-related protein) system. Plasma ghrelin
      levels are decreased in obesity, elevated in cachexia and show a diurnal rhythm.
      Its preprandial elevation suggests, that it might be a signal for meal
      initiation. Ghrelin further stimulates the release of gastric acid and gastric
      motility and affects pancreatic functions. It has vasodilatatory,
      cardioprotective and antiproliferative effects. This article is focused on
      ghrelin's endocrine and metabolic functions.

PMID- 15497932
TI  - Four new dammarane saponins from Zizyphus lotus.
AB  - Five dammarane-type saponins were isolated by means of centrifugal partition
      chromatography from the leaves of Zizyphus lotus. Their structures were
      elucidated using a combination of 1D and 2D 1H and 13C NMR spectra and mass
      spectroscopy. One of these glycosides is the known jujuboside B (5). Three are
      new jujubogenin glycosides, identified as 3-O-alpha-L-rhamnopyranosyl-(1-->6)
      beta-D-glucopyranosyljujubogenin-20-O-(2,3,4-O-triacetyl)-alpha-L
      rhamnopyranoside (1), 3-O-alpha-L-rhamnopyranosyl-(1-->6)-beta-D
      glucopyranosyljujubogenin-20-O-alpha-L-rhamnopyranoside (2), and 3-O-alpha-L
      rhamnopyranosyl-(1-->2)-[(4-sulfo)-beta-D-glucopyranosyl-(1-->3)]-alpha-L
      arabinopyranosyljujubogenin (3). The last is a new sulfated derivative of
      jujubasaponine IV, identified as 3-O-alpha-L-rhamnopyranosyl-(1-->2)-[(4-sulfo)
      beta-D-glucopyranosyl-(1-->3)]-beta-D-galactopyranosyl-(20R,22R)
      16beta,22:16alpha,30-diepoxydammar-24-ene-3beta,20-diol (4).

PMID- 15497933
TI  - Cadinane sesquiterpenes from the brown alga Dictyopteris divaricata.
AB  - Seven new cadinane sesquiterpenes, (-)-(1R,6S,7S,10R)-1-hydroxycadinan-3-en-5-one
      (1), (+)-(1R,5S,6R,7S, 10R)-cadinan-3-ene-1,5-diol (2), (+)-(1R,5R,6R,7S,10R)
      cadinan-3-ene-1,5-diol (3), (+)-(1R,5S,6R,7S,10R)-cadinan-4(11)-ene-1,5-diol (4),
      (+)-(1R,5R,6R,7R,10R)-cadinan-4(11)-ene-1,5,12-triol (5), (-)-(1R,4R,5S,6R,7S,
      10R)-cadinan-1,4,5-triol (6), and (-)-(1R,6R,7S,10R)-11-oxocadinan-4-en-1-ol (7),
      together with nine known compounds were isolated from the brown alga Dictyopteris
      divaricata. The structures of the new natural products, as well as their absolute
      configuration, were established by means of spectroscopic data including IR,
      HRMS, 1D and 2D NMR, single-crystal X-ray diffraction, and CD. All compounds were
      inactive against several human cancer cell lines including lung adenocarcinoma
      (A549), stomach cancer (BGC-823), breast cancer (MCF-7), hepatoma (Bel7402), and
      colon cancer (HCT-8) cell lines.

PMID- 15497934
TI  - Steroids and sesquiterpenoids from the soft corals Dendronephthya gigantea and
      Lemnalia cervicorni.
AB  - One new cytotoxic steroid, dendronesterone A (1), two new steroids,
      dendronesterones B and C (2 and 3), and a known steroid (4) were isolated from
      the methylene chloride solubles of the Formosan soft coral Dendronephthya
      gigantea. Two cytotoxic ylangene-type sesquiterpenoids, lemnalol (5) and the new
      compound cervicol (6), as well as two ylangene-type sesquiterpenoids, isolemnalol
      (7) (a new compound) and 4-oxo-alpha-ylangene (8), were isolated from the
      methylene chloride solubles of the Formosan soft coral Lemnalia cervicorni. Their
      structures were elucidated by 1D and 2D NMR spectral analysis, and their
      cytotoxicity against selected cancer cells was measured in vitro.

PMID- 15497935
TI  - Additional cytotoxic sterols and saponins from the starfish certonardoa
      semiregularis.
AB  - Twelve new (1-7, 9-13) polyhydroxysterols and two new saponins (14 and 15) were
      isolated from the starfish Certonardoa semiregularis by activity-guided
      fractionation. Compounds 1-7 are rare examples of 15-keto steroids from starfish.
      The side chain of compound 11 was also unprecedented in nature. The structures
      were determined by combined spectroscopic methods and chemical derivatization.
      These compounds were evaluated for cytotoxicity against a small panel of human
      solid tumor cell lines, and most of them exhibited considerable activity. One of
      the 15-keto sterols (6) displayed the highest potency, which is comparable to
      that of doxorubicin.

PMID- 15497936
TI  - Dibenzyl bromophenols with diverse dimerization patterns from the brown alga
      Leathesia nana.
AB  - Six novel dibenzyl bromophenols (1-6) with different dimerization patterns and
      two propyl bromophenol derivatives (7 and 8), together with 11 known bromophenol
      derivatives, were isolated from the ethanolic extract of the brown alga Leathesia
      nana. On the basis of spectroscopic methods the structures of the new compounds
      were determined as 5,6'-diethyloxymethyl-3,4,2'-tribromo-2,3',4'
      trihydroxydiphenyl ether (1), 2-(2,3-dibromo-4,5-dihydroxybenzyl)-3,5-dihydroxy-4
      methoxybenzyl alcohol (2), 6-(2,3-dibromo-4,5-dihydroxybenzyl)-2,3-dibromo-4,5
      dihydroxy benzyl methyl ether (3), 9,10-dihydro-9,10-dimethoxy-3,4,7,8-tetrabromo
      1,2,5,6-tetrahydroxyanthracene (4), (+)-3-(2,3-dibromo-4,5-dihydroxyphenyl)-4
      bromo-5,6-dihydroxy-1,3-dihydroisobenzofuran (5), rel-(4aS,10aR)-(+/-)-6,7
      dibromo-4a-hydroxy-3,8-dihydroxymethyl-10a-methoxy-1,4,4a,10a
      tetrahydrodibenzo[b,e][1,4]dioxin-1-one (6), (E)-2-methyl-3-(2,3-dibromo-4,5
      dihydroxyphenyl)propenal (7), and 2-methyl-3-(2,3-dibromo-4,5-dihydroxyphenyl)-1
      propanol (8). Some compounds including 3 showed in vitro selective cytotoxicity
      against several human cancer cell lines. This is the first brown alga to be
      reported containing bromophenols.

PMID- 15497937
TI  - Five new alkaloids from the leaves of Remijia peruviana.
AB  - Three new indolylquinuclidine-type alkaloids, remijinine (1), epiremijinine (2),
      and 5-acetyl-apocinchonamine (3), and two new cinchonine-derived alkaloids, N
      acetyl-deoxycinchonicinol (4) and N-acetyl-cinchonicinol (5), as well as the
      known alkaloids quinamine, conquinamine, cinchonine, and quinidine were isolated
      from the leaves of Remijia peruviana. The structures of the new alkaloids were
      elucidated on the basis of spectroscopic analysis, including homonuclear and
      heteronuclear correlation NMR experiments (COSY, ROESY, HMQC, and HMBC). The
      relative configuration at C-7 for remijinine (1) and, in consequence, for
      epiremijinine (2) was established by X-ray crystal structure analysis of the
      former.

PMID- 15497938
TI  - New pseudopterosin and seco-pseudopterosin diterpene glycosides from two
      Colombian isolates of Pseudopterogorgia elisabethae and their diverse biological
      activities.
AB  - As part of an ongoing program to explore the chemical constituents of Caribbean
      marine invertebrates, a family of 13 new diterpene glycosides, pseudopterosins P
      Z (1-11) and seco-pseudopterosins H (12) and I (13), have been isolated from the
      organic extracts of two collections of the sea whip Pseudopterogorgia elisabethae
      procured near the Colombian Southwestern Caribbean Sea. The structures of
      compounds 1-13, including absolute stereochemistry, have been proposed on the
      basis of comprehensive spectral analyses, chemical transformations, specific
      rotation, and TLC chromatographic analyses. Pseudopterosin Q (2) inhibited
      thromboxane B2 (TXB2) (IC50 = 4.7 microM) and superoxide anion (O2-) (IC50 = 11.2
      microM) generation from E. coli lipopolysaccharide (LPS) activated rat neonatal
      microglia in vitro. In contrast, pseudopterosins P (1), U (6), V (7), W (8), and
      X (9) as well as seco-pseudopterosins H (12) and I (13) demonstrated minimal
      effects on both TXB2 and O2- release. In addition, some of the new compounds
      displayed strong antituberculosis, antiviral, antimalarial, and anticancer
      activity.

PMID- 15497939
TI  - Inhibition of the human chemokine receptor CCR5 by variecolin and variecolol and
      isolation of four new variecolin analogues, emericolins A-D, from Emericella
      aurantiobrunnea.
AB  - An extract from the fungus Emericella aurantiobrunnea was found to compete with
      macrophage inflammatory protein (MIP)-1alpha for binding to human CCR5 in a
      scintillation proximity assay (SPA). Bioassay-guided fractionation led to the
      isolation of variecolin (1) and variecolol (2), which had IC50 values of 9 and 32
      microM, respectively. An X-ray crystal structure of variecolin (1) was obtained
      for the first time. Also isolated were four new inactive analogues, emericolin A
      (3), B (4), C (5), and D (6), and the relative stereochemistry of these compounds
      was determined by NMR methods using ROESY spectra and 1H/1H coupling constants.

PMID- 15497940
TI  - Ingenamine G and cyclostellettamines G-I, K, and L from the new Brazilian species
      of marine sponge Pachychalina sp.
AB  - The chemical investigation of the cytotoxic and antituberculosis active MeOH
      crude extract of the marine sponge Pachychalina sp. led to the isolation of six
      new nitrogenous metabolites, including ingenamine G (1), as well as a mixture of
      new cyclostellettamines G, H, I, K, and L (10-14) with the known
      cyclostellettamines A-F (4-9). Structural assignments of compound 1 were based on
      the analysis of MS and NMR data, while the structures of compounds 10-14 could be
      established by HPLC-MS/MS analysis. Ingenamine G displayed cytotoxic activity
      against HCT-8 (colon), B16 (leukemia), and MCF-7 (breast) cancer cell lines,
      antibacterial activity against Staphylococcus aureus (ATCC 25923), Escherichia
      coli (ATCC 25922), and four oxacilin-resistant S. aureus strains, and
      antimycobacterial activity against Mycobacterium tuberculosis H37Rv.

PMID- 15497941
TI  - Steroidal glycosides from the bulbs of Ornithogalum thyrsoides.
AB  - Phytochemical analyses have been carried out on the fresh bulbs of Ornithogalum
      thyrsoides with particular attention to the steroidal glycoside constituents,
      resulting in the isolation of four new spirostanol saponins and seven new
      cholestane glycosides, together with three known steroidal compounds. The
      structures of the new glycosides were determined on the basis of their
      spectroscopic data, including 2D NMR spectroscopy, and the results of hydrolytic
      cleavage. The isolated compounds were evaluated for their cytotoxic activities
      against HL-60 human promyelocytic leukemia cells and HSC-2 human oral squamous
      cell carcinoma cells.

PMID- 15497942
TI  - Triterpenoids from Brazilian Ilex species and their in vitro antitrypanosomal
      activity.
AB  - From the leaves of Ilex affinis and Ilex buxifolia, two adulterant species of
      "erva mate" (Ilex paraguariensis), three new triterpenoid glycosides were
      isolated. Affinoside 1 (3beta-O-[beta-D-glucopyranosyl-(1-->3)-[2-O-acetyl-(1-
      >2]]-alpha-L-arabinopyranosyl pomolic acid 28-O-beta-D-glucopyranosyl ester, 1)
      was isolated from I. affinis, while buxifolioside I (28-O-beta-D-glucopyranosyl
      ester of (20S)-3alpha,19alpha-dihydroxyurs-12-ene-23,28-dioic acid, 7) and
      buxifolioside II (28-O-beta-D-glucopyranosyl ester of (20S)-3beta,19alpha
      dihydroxyurs-12-en-24,28-dioic acid, 8) were isolated from I. buxifolia. Along
      with these new compounds, ilexoside II (2), ursolic acid (3), 28-nor-ursolic acid
      (4), 3beta-O-acetylursolic acid (5), and uvaol (6) were also isolated. The
      observed results confirm the structural specificity of the I. paraguariensis
      triterpenoids and reinforce a previous proposal to detect mate adulteration by
      triterpenoid analysis. In addition, the in vitro antitrypanosomal activity of
      some Ilex triterpenoids is also reported.

PMID- 15497943
TI  - Isocyanide terpene metabolites of Phyllidiella pustulosa, a nudibranch from the
      South China Sea.
AB  - A series of isocyanides, compounds 4-11, including diterpenes never before found
      in Phyllidiid nudibranchs, have been isolated from a Chinese population of the
      nudibranch Phyllidiella pustulosa. Three new sesquiterpenes (8, 10, and 11), with
      eudesmane, guaiane, and bisabolane skeletons, respectively, have been
      characterized by spectral methods and chemical comparison with known related
      molecules. The absolute stereochemistry of the major metabolite, the isocyanide
      8, an enantiomer of the known sponge metabolite stylotelline (12), has also been
      determined.

PMID- 15497944
TI  - Polyol monoterpenes and sesquiterpene lactones from the Pacific Northwest plant
      Artemisia suksdorfii.
AB  - Five new polyol monoterpenes (1-5) and seven new sesquiterpene lactones (6-12),
      along with five previously identified compounds, were isolated from the aerial
      parts of Artemisia suksdorfii. The structures of the new compounds were
      established by high-field NMR techniques (1H, 13C, 1H-1H DEPT, COSY, HMQC, and
      HMBC) and in case of 6 confirmed by X-ray analysis.

PMID- 15497945
TI  - Novel cassane and cleistanthane diterpenes from Myrospermum frutescens: absolute
      stereochemistry of the cassane diterpene series.
AB  - Four new diterpenes (1-4) were isolated from the leaves of Myrospermum frutescens
      as minor constituents. Chagresnol (1), 6beta,18-diacetoxycassan-13,15-diene (2),
      and chagreslactone (3) possess cassane skeletons, while chagresnone (4) exhibits
      a cleistanthane skeleton. Molecular structures and their relative
      stereochemistries were elucidated using NMR spectroscopy in combination with UV,
      IR, and MS spectral data. Although compound 2 was previously reported as a
      synthetic product, we report its first isolation as a natural product. Derivative
      products (10-13) were obtained to test their activities against Chagas's disease.
      In addition, the absolute stereochemistry of the previously isolated cassane
      diterpene 5 from M. frutescens is presented.

PMID- 15497947
TI  - New indole alkaloids from the roots of Ochrosia acuminata.
AB  - Two new indole alkaloids, polyneuridine-N-oxide (1) and 17-hydroxy-10-methoxy
      yohimbane (2), together with seven known alkaloids were isolated from the roots
      of Ochrosia acuminata collected in Savu, Indonesia. 9-Methoxyellipticine (3) and
      ellipticine (4) were responsible for the antitumor activities of the extract. The
      structures of all compounds were elucidated using MS and NMR methods.

PMID- 15497946
TI  - Marine sesquiterpenoids that inhibit the lyase activity of DNA polymerase beta.
AB  - Bioassay-directed fractionation of an extract of the marine species Spongia sp.
      led to the discovery of the new sesquiterpenoid derivative 17-O
      isoprenyldictyoceratin-C (1), the known sesquiterpenoid derivative dictyoceratin
      C (2), and the sesquiterpenoid quinone ilimaquinone (3), in addition to the
      nucleoside 2'-deoxyuridine. The structure of the new compound 1 was determined on
      the basis of spectroscopic methods and by conversion of dictyoceratin-C (2) to 1.

PMID- 15497948
TI  - Chaetoglobosins Q, R, and T, three further new metabolites from Chaetomium
      globosum.
AB  - Nine cytotoxic metabolites, including three novel compounds, chaetoglobosins Q
      (1), R (2), and T (3), have been isolated from cultures of the fungus Chaetomium
      globosum. The structures were elucidated primarily from NMR spectroscopic data.

PMID- 15497949
TI  - Xanthones from Drimiopsis maculata.
AB  - Six new xanthones, drimiopsins A-F (1-6), have been isolated from the South
      African Drimiopsis maculata. The structures of these compounds were difficult to
      elucidate due to the lack of correlating protons seen in the NMR spectra, and
      INADEQUATE spectra were used to confirm the structures. Xanthones have not
      previously been reported from the Hyacinthaceae.

PMID- 15497950
TI  - Blanchaquinone: a new anthraquinone from an Australian Streptomyces sp.
AB  - Chemical analysis of an Australian Streptomyces species yielded a range of known
      anthracyclines and biosynthetically related metabolites, including daunomycin
      (1), epsilon-rhodomycinone (2), 11-hydroxyauramycinone (3), 11
      hydroxysulfurmycinone (4), aklavinone (5), bisanhydro-gamma-rhodomycinone (6),
      and the anthraquinone 7, as well as the hitherto unreported blanchaquinone (8).
      The structure assigned to 8 was secured by detailed spectroscopic analysis and
      correlation to known analogues, such as the anthraquinone 7. This account also
      represents the first natural occurrence of 3, 4, and 7 and the first
      spectroscopic characterization of 11-hydroxysulfurmycinone (4).

PMID- 15497951
TI  - A novel antimicrobial indolizinium alkaloid from Aniba panurensis.
AB  - Activity-guided fractionation of an Aniba panurensis organic solvent extract has
      led to the isolation of the novel alkaloid 6,8-didec-(1Z)-enyl-5,7-dimethyl-2,3
      dihydro-1H-indolizinium, as the trifluoroacetic acid salt (1). Its structure was
      determined by NMR and mass spectrometry. Bioassays performed in vitro
      demonstrated toxicity of compound 1 to a drug-resistant strain of Candida
      albicans.

PMID- 15497952
TI  - Hyrtiosenolides A and B, two new sesquiterpene gamma-methoxybutenolides and a new
      sterol from a Red Sea sponge Hyrtios species.
AB  - Two new sesquiterpene gamma-methoxybutenolides, hyrtiosenolides A (1) and B (2),
      together with a new 4alpha-methyl polyoxygenated steroid, hyrtiosterol (3), were
      isolated from a Red Sea sponge, Hyrtios species. Their structures were elucidated
      by analysis of their 1D and 2D NMR spectra and HRFABMS. Compounds 1 and 2 showed
      weak antibacterial activity against Escherichia coli.

PMID- 15497953
TI  - Phytochemical studies on Stemona burkillii prain: two new dihydrostemofoline
      alkaloids.
AB  - Two new dihydrostemofoline alkaloids, 11(S),12(R)-dihydrostemofoline (3) and
      stemoburkilline (4), along with stemofoline (1) and 2'-hydroxystemofoline (2)
      have been isolated from a root extract of Stemona burkillii Prain. The structure
      and relative configuration of 3 have been determined via spectroscopic data and
      from comparison with synthetic 11(S),12(S)-dihydrostemofoline (5). The
      configuration of the exo-cyclic alkene group in 4 is tentively assigned as E on
      the basis of mechanistic considerations.

PMID- 15497955
TI  - New sesterterpenes from the sponge Smenospongia sp.
AB  - Five new sesterterpenes, three scalarane-type (1-3) and two linear
      furanosesterterpenes (4, 5), were isolated from the marine sponge Smenospongia
      sp. collected from Gagu-Do, Korea. The structures of the new compounds, which
      exhibited moderate cytotoxicity toward the human leukemia cell line K562, were
      determined from an analysis of spectroscopic data.

PMID- 15497954
TI  - DNA polymerase beta lyase inhibitors from Maytenus putterlickoides.
AB  - During a survey of plant secondary metabolites for DNA polymerase beta lyase
      inhibitors, we found that a crude methyl ethyl ketone extract prepared from
      Maytenus putterlickoides showed strong inhibition of the lyase activity of DNA
      polymerase beta in an in vitro assay. Bioassay-guided fractionation of the
      extract, using an in vitro assay, resulted in the discovery of a new active
      principle, 30-(4'-hydroxybenzoyloxy)-11alpha-hydroxylupane-20(29)-en-3-one (1),
      as well as a known compound, (-)-epicatechin (2). Compounds 1 and 2 exhibited DNA
      polymerase beta lyase inhibitory activity with IC50 values of 62.8 and 18.5
      microM, respectively. Compound 2 was capable of potentiating the action of the
      monofunctional methylating agent methyl methanesulfonate in cultured human cancer
      cells, consistent with the possible utility of inhibitors of this type in vivo.

PMID- 15497956
TI  - Boneratamides A-C, new sesquiterpenoids isolated from the marine sponge Axinyssa
      aplysinoides.
AB  - Three new sesquiterpenoids, boneratamides A (1)-C (3), have been isolated as
      their methyl esters 4-6 from extracts of the marine sponge Axinyssa aplysinoides
      collected in Indonesia. The structures of methyl esters 4-6 were elucidated by
      analysis of spectroscopic data and confirmed by single-crystal X-ray diffraction
      analysis of 4.

PMID- 15497957
TI  - Cyanopeptolin 963A, a chymotrypsin inhibitor of Microcystis PCC 7806.
AB  - A new depsipeptide, cyanopeptolin 963 A (1), was isolated from an axenic strain
      of the toxic freshwater cyanobacterium Microcystis PCC 7806. The structure of
      this compound was elucidated by chemical and spectroscopic analyses, including
      high-resolution ESI-FTICR-MS, 2-D NMR, and GC-MS of the hydrolysate. The major
      structural difference compared to previously characterized cyanopeptolins of this
      strain is the replacement of the basic amino acid in position 3 by L-tyrosine.
      Compound 1 displayed inhibitory activity against chymotrypsin with an IC50 value
      of 0.9 microM.

PMID- 15497958
TI  - Tetradehydrohalicyclamine A and 22-hydroxyhalicyclamine A, new cytotoxic bis
      piperidine alkaloids from a marine sponge Amphimedon sp.
AB  - Two new 3-alkylpiperidine alkaloids, tetradehydrohalicyclamine A (2) and 22
      hydroxyhalicyclamine A (3), have been isolated from a marine sponge Amphimedon
      sp. as cytotoxic constituents. Their structures were elucidated by spectroscopic
      analysis. Compounds 2 and 3 inhibited growth of P388 cells with IC50 values of
      2.2 and 0.45 microg/mL, respectively.

PMID- 15497959
TI  - cis-Eudesmane sesquiterpene glycosides from Liriope muscari and Ophiopogon
      japonicus.
AB  - Two new cis-eudesmane sesquiterpene glycosides, liriopeoside A (1) and
      ophiopogonoside A (2), were extracted and purified from tubers of Liriope muscari
      and Ophiopogon japonicus, respectively, along with three known compounds. Their
      structures were elucidated as 1beta,6beta-dihydroxy-cis-eudesm-3-ene-6-O-beta-D
      glucopyranoside (1) and 1beta,4beta,6beta-trihydroxy-cis-eudesmane-6-O-beta-D
      glucopyranoside (2) by spectral data analysis. The structure and the relative
      configuration of compound 1 were confirmed by X-ray crystallographic analysis.
      This is the first time that cis-eudesmane-type sesquiterpenes have been reported
      from the genera Ophiopogon and Liriope.

PMID- 15497960
TI  - Tichocarpols A and B, two novel phenylpropanoids with feeding-deterrent activity
      from the red alga Tichocarpus crinitus.
AB  - Two novel phenylpropanoic acid derivatives, tichocarpol A (1) and tichocarpol B
      (2), were isolated along with floridoside and isethionic acid from the red alga
      Tichocarpus crinitus. The structures of these novel metabolites were elucidated
      using a combination of spectral (1D and 2D NMR techniques and ESIMS) and chemical
      methods. Compounds 1, 2, and floridoside exhibited feeding-deterrent activity
      against the sea urchin Strongylocentrotus intermedius.

PMID- 15497961
TI  - Antitubercular sesterterpenes from the Thai sponge Brachiaster sp.
AB  - A new scalarane-type sesterterpene, 12-deacetoxyscalarin 19-acetate (2), and two
      naturally new derivatives of manoalide-type sesterterpenes, (E)- and (Z)
      neomanoalide 24,25-diacetates (3 and 4), were isolated from the Thai sponge
      Brachiaster sp., along with five other known sesterterpenes: heteronemin (1),
      heteronemin acetate (5), 12-epi-19-deoxyscalarin (6), 12-deacetyl-12-epi-19
      deoxyscalarin (7), and manoalide 25-acetate (8). The antitubercular and cytotoxic
      activities of all eight compounds were evaluated to reveal the potent activity of
      compounds 1, 2, 5, and 8. Among these, compound 2 showed an interesting
      bioactivity profile, in possessing potent antitubercular activity and being
      practically inactive in the cytotoxicity bioassay.

PMID- 15497963
TI  - Simultaneous assignment of all diastereotopic protons in strychnine using RDCs:
      PELG as alignment medium for organic molecules.
AB  - The concept of using residual dipolar couplings (RDCs) for the structure
      determination of organic molecules is applied to the simultaneous assignment of
      all diastereotopic protons in strychnine. To use this important NMR parameter the
      molecule has to be aligned in the magnetic field. Here we present a new alignment
      medium for organic substrates. The optimization of the alignment properties of
      mixtures of poly-gamma-ethyl-L-glutamate (PELG) and CDCl(3) are described and the
      alignment properties of PELG at different concentrations are evaluated. A
      comparison of PELG with poly-gamma-benzyl-L-glutamate (PBLG) shows considerable
      differences in the magnitude of alignment for strychnine in the two alignment
      media. PELG induces a lower degree of order and makes the measurement of residual
      dipolar couplings (RDCs) in strychnine possible. All one-bond C-H RDCs of
      strychnine in PELG were determined by using 2D heteronuclear single quantum
      coherence (HSQC) spectroscopy. The strategy for the extraction of RDCs for
      methylene groups is described in detail. The RDCs and order parameters are used
      to assign pairs of diastereotopic protons. This methodology can distinguish not
      only one pair of diastereotopic protons but it can be used to assign all pairs of
      diastereotopic protons simultaneously. Two different calculation approaches to
      achieve this task are described in detail.

PMID- 15497964
TI  - Regioselectivity and nucleophilic control in the cyclopropane ring opening of
      duocarmycin SA derivatives under neutral and acid conditions: a quantum
      mechanical study in the gas phase and in solution.
AB  - We present a quantum mechanical investigation of the nucleophilic addition to the
      cyclopropane ring of a representative member of antitumor antibiotics related to
      CC-1065. We have analyzed, in particular, the regioselectivity of the reaction
      and its tuning by the nature of the etheroatom (O or N) in the nucleophile under
      both neutral and acidic conditions. Our results are in agreement with the
      experimental trends and suggest that, contrary to methanol, N-bases can be
      effective also under neutral conditions, irrespective of the additional steric
      constraints experienced in the biologically active substrate (DNA). The
      reliability of the computational protocol, rooted in the density functional
      theory coupled to a refined continuum solvent model, allows us to put forward
      reliable structure/reactivity relationships and to interpret the results in terms
      of reactivity indexes (hardness, electrophilic character).

PMID- 15497965
TI  - Synthesis and spectroscopy of a series of substituted N-confused
      tetraphenylporphyrins.
AB  - A series of N-confused tetraphenylporphyrins (H(2)NCTPPs) with substituents on
      either the para- or the 3,5-positions of the meso phenyl rings were prepared
      using Lindsey conditions. Both electron-withdrawing and electron-donating groups
      were chosen in order to probe the effects of peripheral substitution on the
      properties of the macrocycles. The series includes 5,10,15,20-tetra-(4-R-phenyl)
      N-confused porphyrins (where R = bromo (1), iodo (2), cyano (3), methoxy (4),
      2',5'-dimethoxyphenyl (5), or ethynyl (6)) and 5,10,15,20-(3,5-di-tert
      butylphenyl) N-confused porphyrin (7). Absorption and steady-state fluorescence
      measurements were carried out, and quantum yields were measured for all compounds
      in both dichloromethane (CH(2)Cl(2)) and dimethylacetamide (DMAc).

PMID- 15497966
TI  - Eremophilane sesquiterpenes from capsidiol.
AB  - A series of eremophilane sesquiterpene alcohols and hydrocarbons was prepared
      from the phytoalexin capsidiol (1) for mechanistic studies with epiaristolochene
      synthase and epiaristolochene dihydroxylase. Among them, 3-deoxycapsidiol (10)
      was obtained through selective derivatization and reductive cleavage of the
      equatorial 3 alpha hydroxyl group. Two novel isomers of aristolochene and
      eremophilene were accessed from the 1- and 3-deoxycapsidiol isomers. 4
      Epieremophilene (17) was obtained by conjugate reduction of epiaristolochen-1-one
      tosylhydrazone with catecholborane followed by sulfinate elimination and diimide
      rearrangement. Epimerization of epiaristolochen-3-one (27a) at the C4 methyl
      followed by reductions led to the previously unknown aristolochene isomer,
      eremophila-9(10),11(12)-diene (30). Optical rotations and characteristic (1)H NMR
      data for the related eremophilenols and dienes are collected in Tables 1 and 2.
      Finally, bioassays were used to assess the antifungal potencies of capsidiol and
      its synthetic derivatives. The minimum inhibitory concentration for capsidiol (3
      10 ng) was at least 1 order of magnitude lower than that of any of the
      derivatives and considerably lower than those previously reported for
      ketoconazole, nystatin, and propiconazole.

PMID- 15497967
TI  - Rational design of CH/pi interaction sites in a basic resolving agent.
AB  - A novel synthetic basic resolving agent, cis-1-aminobenz[f]indan-2-ol (ABI), was
      rationally designed by introducing effective CH/pi interaction sites to cis-1
      aminoindan-2-ol (AI), whose chiral recognition ability has been reported from our
      laboratory. ABI was applicable to a wide variety of racemic arylalkanoic acids
      and showed moderate to excellent chiral recognition ability, which was obviously
      higher than that of AI. The fundamental and important role of CH/pi interactions,
      such as tunable CH(sp(2))/pi and CH(sp(3))/pi interactions, in the chiral
      recognition by ABI was revealed by X-ray crystallographic study.

PMID- 15497968
TI  - Stereochemical features of Lewis acid-promoted glycosidations involving 4'
      spiroannulated DNA building blocks.
AB  - Tin tetrachloride-catalyzed glycosidation of persilylated nucleobases with
      acetate donor 6 in CH(2)Cl(2) solution followed by deprotection gave rise very
      predominantly to alpha-spironucleosides. These stereochemical assignments stem
      from the determination of NOE interactions and an X-ray crystallographic analysis
      of the latter product. Computational studies revealed that these results are
      consistent with the fact that the C5' substituent shields the beta-face of the
      oxonium ion involved in the coupling reaction while the C3' substituent is
      projected away from the alpha-underside. Attack from the more open direction is
      therefore kinetically favored. Entirely comparable calculations suggested that
      donor 19 should behave comparably. Experimentation involving this donor gave
      results consistent with this model although more equitable alpha/beta
      spironucleoside product ratios were seen when acetonitrile was employed as the
      reaction medium.

PMID- 15497969
TI  - Molecular recognition of carbohydrates with acyclic pyridine-based receptors.
AB  - The recognition capabilities of acyclic pyridine-based receptors toward
      monosaccharides were evaluated. Aminopyridine receptors based on the 2,4,6
      trimethyl- or 2,4,6-triethylbenzene frame show high beta vs alpha binding
      selectivity in the recognition of glucopyranosides. Amidopyridine receptors,
      which are sterically less hindered at nitrogen, display high efficiency and an
      inverse selectivity. The 2-aminopyridine group has been established as a highly
      effective recognition group in the binding of monosaccharides. The factors
      influencing the binding properties of receptors 1-15, which differ in the nature
      and number of binding and spacer subunits used as the buildings blocks, are
      discussed.

PMID- 15497970
TI  - Design and efficient synthesis of 2 alpha-(omega-hydroxyalkoxy)-1 alpha,25
      dihydroxyvitamin D3 Analogues, including 2-epi-ED-71 and their 20-epimers with HL
      60 cell differentiation activity.
AB  - A concise and efficient synthetic approach to 2 alpha-(omega-hydroxyalkoxy)-1
      alpha,25-dihydroxyvitamin D(3) (4a-c), including 2-epi-ED-71, was developed
      starting from D-glucose as a chiral template for the construction of the 2 alpha
      modified A-ring precursors (11a-c). It was found that the best ligand for the
      bovine thymus vitamin D receptor (VDR) in this series is 4b, which has 1.8 times
      greater binding affinity for the bovine thymus VDR than that of the natural
      hormone 1. Interestingly, potency in the induction of HL-60 cell differentiation
      for 4a-c was almost the same or weaker than that of 1 despite the strong binding
      affinity for the VDR. Next, we were interested in the "double modification"of 1
      based on 4a-c with C20-epimerization, affording 2 alpha-(omega-hydroxyalkoxy)-20
      epi-1 alpha,25-dihydroxyvitamin D(3) (20-epi-4a-c). All three 2 alpha-substituted
      20-epi analogues of 1 (20-epi-4a-c) exhibited stronger binding affinities for the
      VDR, and their conformations in the ligand binding domain of VDR were analyzed by
      molecular modeling. Double-modified analogues of 20-epi-4a-c showed marked HL-60
      cell differentiation activity, and 20-epi-4a possesses an activity 58-fold higher
      than that of the natural hormone 1.

PMID- 15497971
TI  - Synthesis and evaluation of new substrate analogues of streptomyces R61 DD
      peptidase: dissection of a specific ligand.
AB  - Good substrates of the Streptomyces R61 dd-peptidase, such as glycyl-L-alpha
      amino-epsilon-pimelyl-D-alanyl-D-alanine, 1 (Anderson, J. W.; Pratt, R. F.
      Biochemistry 2000, 39, 12200-12209), contain the glycyl-L-alpha-amino-epsilon
      pimelyl side chain. A number of thia variants of this structure have been
      synthesized by means of a disconnection strategy whereby the appropriate thiols
      were reacted with either acryloyl-D-alanyl-D-alanine or haloalkanoyl-D-alanyl-D
      alanines. Kinetics studies of the hydrolysis of these compounds by the R61 DD
      peptidase showed that the presence of the N-terminal glycylammonium ion and the
      pimelyl-alpha-carboxylate are very important for efficient catalysis. The results
      of deletion of the C-terminal D-alanine indicate a promising direction toward new
      inhibitors. Shorter (one methylene less) and longer (one methylene more)
      analogues of 1 are also poor substrates. Molecular modeling and dynamics studies
      suggest that the higher mobility of the active site residues and the modified
      substrates in enzyme-substrate complexes may be the dominant factor in this loss
      of reactivity. The general conclusion is that essentially all of the structural
      elements of the side chain of 1 are required to produce a good substrate. This
      result has important implications for the design of inhibitors of DD-peptidases.

PMID- 15497972
TI  - New paradigms for the peroxy acid epoxidation of CC double bonds: the role of the
      peroxy acid s-trans conformer and of the 1,2-H transfer in the epoxidation of
      cyclic allylic alcohols.
AB  - RB3LYP calculations, on reaction of performic acid with cyclic allylic alcohols,
      demonstrate that the less stable s-trans conformer of peroxy acids can be
      involved in epoxidations of C=C bonds. Transition structures (TSs) arising from s
      trans performic acid retain some of the well-established characteristics of the
      TSs of the s-cis isomer such as the perpendicular orientation of the O-H peroxy
      acid bond relative to the C=C bond and a one-step oxirane ring formation. These
      TSs are very asynchronous but collapse directly (without formation of any
      intermediate) to the final epoxide-peroxy acid complex via a 1,2-H shift. Thus,
      our findings challenge the traditional mechanism of peroxy acid epoxidation of
      C=C bonds by demonstrating that the involvement of the s-trans isomer opens an
      alternative one-step reaction channel characterized by a 1,2-H transfer. This
      novel reaction pathway can even overcome, in the case of the reaction of cyclic
      allylic alcohols in moderately polar solvents (e.g., in dichloromethane), the
      classical Bartlett's mechanism that is based on the s-cis peroxy acid form and
      that features a 1,4-H shift. However, the latter mechanism remains strongly
      favored for the epoxidation of normal alkenes.

PMID- 15497973
TI  - Theoretical analysis of Lewis basicity based on local electron-donating ability.
      Origin of basic strength of cyclic amines.
AB  - It has been experimentally established that the proton affinities (PA), as well
      as the solution basicities (pK(BH)(+)), of aziridine derivatives are much smaller
      than those of the corresponding pyrrolidines and piperidines, though the basic
      strength of azetidines is close to those of pyrrolidines and piperidines. A
      simple idea of dependence of the basic strength on bond angles seems to be
      invalid. Because the basicity of cyclic amines is a fundamental property in
      organic chemistry, we revisited this topic in order to clarify quantitatively the
      intrinsic origin of the strength of Lewis basicity of the relevant amines, in
      particular, based on the local electron-donating ability of the amine nitrogen
      atoms evaluated in terms of the localized reactive hybrid orbital (RHO) concept.
      In the cases of representative N-substituents such as hydrogen, methyl, and
      phenyl groups, the electron-donating energy level of the nitrogen center,
      obtained by maximizing a kind of superdelocalizability, was shown to be
      correlated with the magnitudes of experimental and calculated gas-phase proton
      affinities. The present results strongly support the view that the C-N-C bond
      angle, i.e., angle strain, in the cyclic amines is not the major source of the
      difference in strength of basicity of these amines, but rather, the degree of
      pyramidalization around the nitrogen atom has a significant impact on the
      electron-donating ability of the nitrogen lone-pair orbital.

PMID- 15497974
TI  - Novel autoxidative cleavage reaction of 9-fluoredenes discovered during synthesis
      of a potential DNA-threading indenoisoquinoline.
AB  - The indenoisoquinolines are a novel class of cytotoxic non-camptothecin
      topoisomerase I inhibitors. A potential DNA-threading agent was designed by
      attaching different amine side chains on the lactam nitrogen as well as on the
      C11 position of the indenoisoquinoline ring system. It was hypothesized that
      substituents on the lactam nitrogen could protrude out toward the DNA major
      groove while those on the C11 project out toward the DNA minor groove in the
      ternary "cleavage complex." Compound 4 was synthesized in order to test this DNA
      threading scenario. It was found unexpectedly that an alkenyl substituent on the
      C11 position was autoxidatively cleaved under basic conditions to afford a
      ketone. A possible mechanism for this unusual oxidative cleavage was proposed on
      the basis of the studies of a 9-fluoredene model compound. The proposed mechanism
      was further supported by computational studies. Although the designed compound 4
      showed potent cytotoxicities in various cancer cell lines, it was less potent
      than its nonthreading counterparts and was not a topoisomerase I inhibitor.

PMID- 15497975
TI  - C2-symmetric diphosphinite ligands derived from carbohydrates. The strong
      influence of remote stereocenters on asymmetric rhodium-catalyzed hydrogenation.
AB  - Modular ligands of C(2) symmetry (13a-e, 14a,b,d, and ent-9), systematically
      modified at positions 2 and 5, were easily prepared from d-glucosamine, D
      glucitol, and tartaric acid, respectively. The application of these ligands in
      the rhodium-catalyzed hydrogenation of methyl acetamidoacrylate, methyl
      acetamidocinnamate, and dimethyl itaconate shows that both the configuration and
      the substituents at positions 2 and 5 of the tetrahydrofuran backbone have a
      strong influence on the enantioselectivty of the processes.

PMID- 15497976
TI  - Can simple enones be useful partners for the catalytic stereoselective alkylation
      of indoles?
AB  - A new catalytic system for the first example of enantioselective Friedel-Crafts
      type (FC) addition of indoles to simple enones is described. The use of an
      equimolar amount of chiral [Al(salen)Cl] and 2,6-lutidine (10 mol %) was found to
      be effective in promoting the conjugate addition of indoles to (E)-arylcrotyl
      ketones, furnishing the corresponding beta-indolyl ketones in excellent yield and
      high enantioselectivity (ee up to 89%). The role of the base was investigated
      through spectroscopic as well as computational analyses, which suggested that in
      situ formation of a new chiral (base.[Al(salen)]) complex was operating under our
      reaction conditions. In particular, a stable cationic [Al(salen)] hexacoordinate
      trans complex with the additive base and the enone is suggested as being
      responsible for the stereocontrolled reaction. Finally, detailed monitoring of
      the reaction course was carried out showing that a conventional FC pathway
      induced by [Al(salen)Cl] acting as a Lewis acid is operating.

PMID- 15497977
TI  - Structure, bonding, and solvation of dilithiodiamines.
AB  - Computational methods were used to determine the structure of dilithiodiamines
      and the effects of solvation by ethereal solvents. Solvation was examined by the
      use of microsolvation with explicit dimethyl ether or THF ligands and by the
      combined use of microsolvation and the IEFPCM continuum solvent model. It was
      determined that each of the compounds studied exists exclusively as a bridged
      intramolecular dimer, both in the gas phase and in solution. Thermodynamic
      properties were calculated at 200 and 298 K to estimate the effect of temperature
      on the cyclization energies. Infrared spectroscopy was used to confirm the
      proposed intramolecular dimer structures.

PMID- 15497978
TI  - Experimental and theoretical studies of fused-ring persistent [1,2,4]thiadiazinyl
      radicals.
AB  - Five persistent radicals 1a-1e were generated by the oxidation of 4H
      [1,2,4]thiadiazines 2a-2e and studied with ESR and UV-vis spectroscopy. Three of
      the radicals, 1a, 1d, and 1e, were generated in high yields (>90%) using either
      SO(2)Cl(2)/amine in toluene or AgO/K(2)CO(3) in a toluene/MeCN mixture.
      Halogenated radicals 1d and 1e were sufficiently stable for chromatographic
      isolation and vacuum sublimation. The solution stability of the fluorinated 1d
      was measured at t(1/2) approximately 4 months in the absence of oxygen, and 1e at
      t(1/2) approximately 40 min in the presence of air. The crystal and molecular
      structures of 1d were determined by X-ray crystallography showing columns of
      parallel almost evenly spaced planar heterocycles connected by infinite
      ...N...S... chains. Cyclic voltammetry of 1d and 1e shows reversible reduction
      waves at about 0 V and irreversible oxidations at about 1.2 V. Spectral and
      electrochemical properties of 1 were well reproduced by DFT methods.

PMID- 15497979
TI  - Local aromaticity of the six-membered rings in pyracylene. A difficult case for
      the NICS indicator of aromaticity.
AB  - In this work, we have analyzed the local aromaticity of the six-membered rings (6
      MRs) of planar and pyramidalized pyracylene species through the structurally
      based harmonic oscillator model of aromaticity (HOMA), the electronically based
      para-delocalization index (PDI), and the magnetic-based nucleus independent
      chemical shift (NICS) measurements, as well as with maps of ring current density.
      According to ring currents and PDI and HOMA indicators of aromaticity, there is a
      small reduction of local aromaticity in the 6-MRs of pyracylene with a bending of
      the molecule. In the case of NICS, the results depend on whether the NICS value
      is calculated at the center of the ring (NICS(0)) or at 1 A above (NICS(1)(out))
      or below (NICS(1)(in)) the ring plane. While NICS(1)(out) values also indicate a
      slight decrease of aromaticity with bending, NICS(0) and NICS(1)(in) wrongly
      point out a large increase of aromaticity upon distortion. We have demonstrated
      that the NICS(0) reduction in the 6-MRs of pyracylene upon bending is due to (a)
      a strong reduction of the paratropic currents in 5-MRs and (b) the fact that, due
      to the distortion, the paratropic currents point their effects in other
      directions.

PMID- 15497980
TI  - Synthesis of a 1'-aminomethylthymidine and oligodeoxyribonucleotides with 1'
      acylamidomethylthymidine residues.
AB  - Reported here is a 10-step synthesis of a phosphoramidite building block of 1'
      aminomethylthymidine that starts from 2-deoxyribose. The framework of the
      branched aminonucleoside was elaborated from a known 1-cyano-1-bromo glycosyl
      donor, whose reaction with the silylated nucleobase furnished the 1'-cyanide,
      which was reduced to the desired aminomethylnucleoside. The N-allyloxycarbonyl
      (Alloc)-protected nucleoside was converted to a phosphoramidite building block
      and incorporated into the oligonucleotides 5'-GCAT*TATTAC-3', and 5'-GCAT*TAT*TAC
      3', where T* denotes 1'-acylamidomethylthymidine residues. Removal of the Alloc
      protecting group and acylation with the residue of pyrene-1-yl-butanoic acid were
      achieved on support, using microwave irradiation to ensure full conversion. The
      UV-melting point of the duplex of the singly and doubly modified decamers with
      their fully complementary target sequence is 0.1-6.9 degrees C higher than that
      of the unmodified control duplex, depending on the salt concentration. This
      suggests that the aminomethyl linker may allow for the placing of a functional
      "payload" in the minor groove of DNA duplexes without disrupting the helix.
      Oligonucleotides thus endowed with functional modifications may become useful for
      biomedical applications.

PMID- 15497981
TI  - Palladium-catalyzed addition of mono- and dicarbonyl compounds to conjugated
      dienes.
AB  - An intermolecular, palladium-catalyzed addition of the alpha-C-H bond of
      monocarbonyl and 1,3-dicarbonyl compounds to dienes has been developed, and an
      exploration of the scope of these reactions with a broad range of carbonyl
      compounds and nitriles was conducted. The combination of CpPd(allyl) and the
      commercially available 1,3-bis(dicyclohexylphosphino)propane (DCyPP) catalyzed
      the 1:1 addition of the C-H bonds of these substrates to dienes in high yields.
      These reactions included unusual additions of the C-H bonds of ketones, lactones,
      esters, and nitriles to dienes, as well as the more common additions of
      cyanoesters, malononitrile, and alpha-sulfonyl esters. Reactions of these
      substrates with both cyclic and acyclic dienes are reported. Reactions catalyzed
      by complexes of nonracemic chiral ligands were also conducted, and the first
      enantioselective version of this reaction was achieved with a Josiphos ligand
      with enantioselectivities up to 81%.

PMID- 15497983
TI  - Nucleophilicities of nitroalkyl anions.
AB  - The kinetics of the reactions of eight nitroalkyl anions (nitronate anions) with
      benzhydrylium ions and quinone methides in DMSO and water were investigated
      photometrically. The second-order rate constants were found to follow a Ritchie
      constant selectivity relationship with slightly smaller selectivities than those
      observed previously for other carbanions and O or N nucleophiles. Evaluation of
      the kinetic data by the correlation equation log k (20 degrees C) = s(N + E)
      yields the nucleophilicity parameters (N), which allow a comparison of the
      nucleophilicities of nitronates with those of other classes of compounds.
      Although the aliphatic nitronates 1a-c are more nucleophilic than the aromatic
      representatives 1d-h in DMSO, hydration reduces the nucleophilicities of
      aliphatic nitronates by a factor of 1 million, which is considerably greater than
      the reduction of the reactivities of the aromatic nitronates with the consequence
      that aromatic nitronates are more nucleophilic in water than aliphatic ones. The
      nucleophilic reactivities of nitronates are only slightly affected by substituent
      variation in DMSO and even less so in aqueous solution, which is considered to be
      the reason for the unusual rate equilibrium relationships, the so-called
      nitroalkane anomaly. Outer-sphere electron transfer does not occur in any of the
      reactions that were investigated.

PMID- 15497982
TI  - Diastereoselective syntheses of deoxydysibetaine, dysibetaine, and its 4-epimer.
AB  - (+/-)-Deoxydysibetaine 2 and 4-epi-dysibetaine 3 were prepared in a few steps
      from methyl pyroglutamate through a regioselective Mannich reaction at C-2.
      Natural (2S,4S)-dysibetaine 1, a sponge metabolite isolated from Dysidea
      herbacea, and (2S)-2 were synthesized from enantiopure (S)-pyroglutaminol with
      very high stereoselectivity. The key steps were an original formation of
      stereogenic quaternary center C-2 and the diastereoselective hydroxylation at C
      4.

PMID- 15497984
TI  - Synthesis of Chiral beta 3-aminoxy peptides.
AB  - A series of chiral beta(3)-aminoxy acids or amides with various side chains have
      been synthesized via two different approaches. One is the Arndt-Eistert
      homologation approach, using chiral alpha-aminoxy acids as starting materials.
      The other approach, utilizing the enantioselective reduction of beta-keto esters
      catalyzed by baker's yeast or chiral Ru(II) complexes, produces chiral beta(3)
      aminoxy acids with nonproteinaceous side chains. The oligomers of beta(3)-aminoxy
      acids can be readily prepared using EDCI/HOAt as the coupling reagent.

PMID- 15497985
TI  - Photochemical preparation of highly functionalized 1-indanones.
AB  - A series of o-alkylphenyl alkyl ketones 1 were synthesized by different methods.
      The presence of a leaving group X adjacent to the carbonyl group is the special
      peculiarity of these ketones. Upon irradiation the keto carbonyl group of these
      compounds undergoes an n-pi* excitation followed by a 1,5-hydrogen migration from
      the o-alkyl substituent to the carbonyl oxygen atom. The thus formed 1,4
      diradicals are subject to a very rapid elimination of acid HX, giving 1,5
      diradicals. We called this process spin center shift. After intersystem crossing
      these diradicals cyclize to 1-indanones 20 in good yields. Depending on the
      solvent and on substituents, o-alkoxyalkyl ketones 22 or benzo[c]furanes 21 are
      obtained as byproducts. The mechanism of the cyclization was elucidated by
      quantum chemical calculations and kinetic measurements.

PMID- 15497986
TI  - Synthesis of allylsilanes by reductive lithiation of thioethers.
AB  - Although much work in reductive lithiation has been done, the utilization of
      allylthioethers bearing various substituents to prepare allylsilanes has not been
      explored. The main reason clearly stems from the anticipated lack of
      regioselectivity. We describe herein the first study on the regioselectivity of
      the reductive silylation involving dissymmetric allylthioethers. We surveyed a
      broad spectrum of parameters and showed that this process displays a great
      dependence of the reaction conditions. We also discovered that an electron
      transporter, DBB or naphthalene, can cleave THF at room temperature by
      sonication, to generate a strong base, 4-lithiobutoxide. This feature was
      successfully exploited to the straightforward synthesis of bis-silanes in one
      pot. Examples are provided for maximizing both the chemical yield and the
      regioselectivity of the reductive silylation through the tuning of the reaction
      conditions. By changing these conditions, several allylsilanes can be selectively
      synthesized from one thioether.

PMID- 15497987
TI  - Acid-catalyzed reactions of aromatic aldehydes with ethyl diazoacetate: an
      investigation on the synthesis of 3-hydroxy-2-arylacrylic acid ethyl esters.
AB  - Several commercial Lewis acids, including those of the Bronsted type,
      specifically HBF(4).OEt(2), are able to catalyze the reaction between aromatic
      aldehydes and ethyl diazoacetate to produce 3-hydroxy-2-arylacrylic acid ethyl
      esters and 3-oxo-3-arylpropanoic acid ethyl esters. Reactions catalyzed by the
      iron Lewis acid [(eta(5)-C(5)H(5))Fe(+)(CO)(2)(THF)]BF(4)(-) (i.e., 1) have the
      best yields and greatest ratio of 3-hydroxy-2-arylacrylic acid ethyl ester. The
      product distribution of 1 is not affected in the presence of Proton Sponge, but
      is dependent on temperature and the nature of the substrate aldehyde, whereas the
      activity of HBF(4).OEt(2) is affected by the presence of Proton Sponge and is
      reactive at temperatures as low as -78 degrees C. Consequently, both 1 and
      HBF(4).OEt(2) are valuable catalysts in producing important 3-hydroxy-2
      arylacrylic acid ethyl esters as precursors to biologically active compounds.

PMID- 15497988
TI  - Solid-phase synthesis of oligonucleotide glycoconjugates bearing three different
      glycosyl groups: orthogonally protected bis(hydroxymethyl)-N,N'-bis(3
      hydroxypropyl)malondiamide phosphoramidite as key building block.
AB  - Diethyl O,O'-(methoxymethylene)bis(hydroxymethyl)malonate (3) was observed to
      undergo a stepwise aminolysis when treated with 3-aminopropanol. This allowed
      convenient preparation of bis(hydroxymethyl)-N,N'-bis(3
      hydroxypropyl)malondiamide bearing orthogonal levulinyl (Lev) and tert
      butyldiphenylsilyl (TBDPS) protections at the two N-hydroxypropyl groups (8). One
      of the hydroxylmethyl functions was then protected with a 4,4'-dimethoxytrityl
      (DMTr) group, and the other one was phosphitylated to obtain a methyl N,N
      diisopropylphosphoramidite (1). This building block was used for the synthesis of
      oligonucleotide glycoconjugates (25 and 26) carrying three different sugar units.
      After conventional phosphoramidite chain assembly of the sequence containing 1,
      the 5'-terminal DMTr group was removed and an appropriate glycosyl 6-O
      phosphoramidite was coupled. The remaining protections of the branching unit were
      removed in the order of Lev and TBDPS, and the exposed hydroxyl functions were
      reacted one after another with the desired glycosyl 6-O-phosphoramidites. Global
      deprotection and cleavage of the conjugate from the support were achieved by
      conventional ammonolysis.

PMID- 15497989
TI  - Preparation and regioselective SN2' reaction of novel gem-difluorinated
      vinyloxiranes with RLi.
AB  - A series of hitherto unknown 3,4-epoxy-1,1-difluorobutenes were prepared from the
      readily accessible alpha,beta-epoxy ketones and these compounds were found to
      undergo regioselective S(N)2' reactions with hard RLi nucleophiles occurring at
      the highly positively charged terminal fluorine-possessing sp(2) carbon atom in
      quite sharp contrast to the cases of the corresponding nonfluorinated
      vinyloxiranes which only attained a low level of regioselectivity. Addition of
      HMPA substantially improved the products' olefinic stereoselectivity. Theoretical
      calculations were used to qualitatively explore the nature of selectivity in
      these reactions.

PMID- 15497990
TI  - Electronic structure of persistent radicals: nitroxides.
AB  - The molecular and electronic structures of 10 free nitroxide radicals have been
      investigated by HeI/HeII photoelectron spectroscopy (UPS), DFT calculations, and
      comparison with the spectra of related compounds. We observe that the electronic
      structure of the nitroxide group is unaffected by substitution except in a
      carbonyl derivative where nitroxide group orbitals are noticeably stabilized.
      Also, we have detected small variations in the photoionization cross-sections for
      singlet and triplet states of cation, the states belonging to the same electron
      configuration. The relationship between electronic structure and radical
      reactivity is discussed, and an experimentally based estimate of delocalization
      energy of the unpaired electron is given. Some conflicting kinetic data on
      radical reactivity have been analyzed in view of the UPS results.

PMID- 15497991
TI  - Phosphaadamantanes as ligands for palladium catalyzed cross-coupling chemistry:
      library synthesis, characterization, and screening in the Suzuki coupling of
      alkyl halides and tosylates containing beta-hydrogens with boronic acids and
      alkylboranes.
AB  - A 15-member library of phosphaadamantane ligands has been prepared via P
      arylation of 1,3,5,7-tetramethyl-2,4,8-trioxa-6-phosphaadamantane. Screening of
      this tertiary phosphine collection has allowed for the rapid determination of the
      most suitable ligand, specifically 1,3,5,7-tetramethyl-6-(2,4-dimethoxyphenyl)
      2,4,8-trioxa-6-phosphaadamantane, for facilitating Suzuki-type couplings of alkyl
      halides or tosylates containing beta-hydrogens with either boronic acids or
      alkylboranes.

PMID- 15497992
TI  - Azolium-linked cyclophanes: a comprehensive examination of conformations by 1H
      NMR spectroscopy and structural studies.
AB  - The synthesis and characterization of a series of azolium-linked cyclophanes are
      reported. The cyclophanes consist of two azolium groups (17 examples) or three
      imidazolium groups (1 example) linked to two benzenoid units (benzene,
      naphthalene, p-xylene, mesitylene, 1,2,3,4- and 1,2,4,5-tetramethylbenzene, 2,6
      pyridine, and p-tert-butylphenol) via methylene groups. Cyclophanes containing
      ortho-, meta-, and para-substitution patterns in the benzenoid units were
      examined. The conformations of the cyclophanes were examined in solution by
      variable-temperature NMR studies and in the solid state by crystallographic
      studies. The p-cyclophanes and mesitylene-based m- and o/m-cyclophanes are rigid
      on the NMR time scale, as indicated by sharp (1)H NMR spectra at all accessible
      temperatures. The non-mesitylene-based m-cyclophanes and the o-cyclophanes are
      fluxional on the NMR time scale at high temperatures, but in most cases, specific
      conformations can be "frozen out" at low temperatures. Many structures deduced
      from solution studies were consistent with those in the solid state.

PMID- 15497993
TI  - Stereochemistry of C-6 nucleophilic displacements on 1,1
      difluorocyclopropyldibenzosuberanyl substrates. An improved synthesis of
      multidrug resistance modulator LY335979 trihydrochloride.
AB  - Studies of the displacement chemistry of 1,1-difluorocyclopropyldibenzosuberanyl
      alcohol 4 and its activated bromide derivative 6 have led to an improved approach
      to anti-2, a key precursor to LY335979 3HCl (1). Bromination of either syn-4 or
      anti-4 gave anti-oriented 6, indicating thermodynamically controlled product
      stereochemistry via a stabilized 1,1-difluorohomotropylium ion intermediate.
      Reaction of 6 with piperazine proceeded irreversibly to provide an isomeric
      mixture of piperazine products, with the syn:anti product ratio increased by
      solvent effects. Reaction of 6 with pyridine and pyrazine, on the other hand,
      gave anti-pyridinium and pyrazinium salts, respectively, apparently via
      equilibration of initially formed syn products. Reduction of pyrazinium salt 11
      with lithium borohydride/TFA provided anti-2 unaccompanied by its syn isomer. A
      practical and expeditious approach to 1 was derived from these new results.

PMID- 15497994
TI  - Substituent effects on the Z/E-selectivity in cross-metathesis of conjugated
      enynes.
AB  - Cross-metathesis of a range of conjugated enynes with alkenes turns out to
      proceed with preferential formation of Z-isomers over E-isomers up to >25:1.
      Careful studies including substrate modification and control experiments revealed
      that the reaction proceeds under kinetic rather than thermodynamic control.
      Driving forces for this substrate-dependent Z-selectivity are attributed to the
      steric hindrance between substituents on the reacting enynes and NHC ligand of
      the ruthenium catalyst in the putative metallacyclobutane, as well as chelation
      effects of suitably positioned functional groups to Ru, which is strongly
      supported by ab initio calculations.

PMID- 15497995
TI  - Synthesis of the enantiomers of hexahydrodibenz[d,f]azecines.
AB  - Suzuki coupling procedures were used to make appropriate 2-(3-aminopropyl)- 2'-(2
      mesyloxy)ethyl disubstituted biphenyl derivatives 19 and 20 from which the
      racemic hexahydrodibenz[d,f]azecines 3 and 4 were produced following
      intramolecular mesyloxy displacement in dilute solution. The enantiomers of the
      former azecine were prepared by use of an analogue of the biphenyl aminomesylate
      19 having a chiral auxiliary bound to the amino group during the closure of the
      10-membered ring. Absolute configurations were assigned by X-ray diffraction
      analysis of compound 28.

PMID- 15497996
TI  - Ruthenium-catalyzed olefin metathesis double-bond isomerization sequence.
AB  - A novel ruthenium-catalyzed tandem ring-closing metathesis (RCM) double-bond
      isomerization reaction is described in this paper. The utility of this method for
      the efficient syntheses of five-, six-, and seven-membered cyclic enol ethers is
      demonstrated. It relies on the conversion of a metathesis-active ruthenium
      carbene species to an isomerization-active ruthenium-hydride species in situ.
      This conversion is achieved by using various additives. Scope and limitations of
      the different protocols are discussed, and some mechanistic considerations based
      on (31)P and (1)H NMR spectroscopic studies are presented.

PMID- 15497997
TI  - Vanadium-catalyzed sulfenylation of indoles and 2-naphthols with thiols under
      molecular oxygen.
AB  - Vanadium oxyacetylacetonate [VO(acac)(2)] works as a catalyst for the direct
      synthesis of 3-sulfanylindoles from indoles and thiols under an atmospheric
      pressure of molecular oxygen as a reoxidant. For example, the reaction of 2
      phenylindole with benzenethiol in the presence of a catalytic amount of
      VO(acac)(2), potassium iodide, and 2,6-di-tert-butyl-p-cresol in chlorobenzene
      under molecular oxygen proceeds to afford 2-phenyl-3-(phenylsulfanyl)indole in
      86% yield. This catalytic system can also be applied to 2-naphthols instead of
      indoles to give the corresponding 1-sulfanyl-2-naphthols in up to 57% yield.

PMID- 15497998
TI  - An efficient preparation of isosteric phosphonate analogues of sphingolipids by
      opening of oxirane and cyclic sulfamidate intermediates with alpha-lithiated
      alkylphosphonic esters.
AB  - D-erythro-(2S,3R,4E)-Sphingosine-1-phosphonate (1), the isosteric phosphonate
      analogue of naturally occurring sphingosine 1-phosphate (1a), and D-ribo
      phytosphingosine 1-phosphonate (2), the isosteric phosphonate analogue of D-ribo
      phytosphingosine-1-phosphate (2a), were synthesized starting with methyl 2,3-O
      isopropylidene-d-glycerate (4) and D-ribo-phytosphingosine (3), respectively.
      Oxirane 12 was formed in eight steps from 4, and cyclic sulfamidate 22 was formed
      in five steps from 3. The phosphonate group was introduced via regioselective
      ring-opening reactions of oxirane 12 and cyclic sulfamidate 22 with lithium
      dialkyl methylphosphonate, affording 13 and 23, respectively. The synthesis of 1
      was completed by S(N)2 displacement of chloromesylate intermediate 14b with azide
      ion, followed by conversion of the resulting azido group to a NHBoc group and
      deprotection. The synthesis of 2 was completed by cleavage of the acetal, N
      benzyl, and alkyl phosphonate ester groups.

PMID- 15497999
TI  - Ruthenium-catalyzed cyclization of alkyne-epoxide functionalities through
      alternation of the substituent and structural skeleton of epoxides.
AB  - Treatment of 1-(o-ethynylphenyl)-2-alkyl-2-aryl epoxides with
      TpRuPPh(3)(CH(3)CN)(2)PF(6) catalyst (10 mol %) in hot toluene (100 degrees C, 12
      h) led to an atypical cyclization and gave 1-aryl-2-alkyl-1H-indene derivatives
      and carbon monoxide efficiently. The cyclization of 1-cis-enynyl-2-alkyl epoxides
      with this catalyst in hot toluene (10 mol %, 100 degrees C, 12 h) gave 2,5
      disubstituted phenols in 45-72% yields. Under the same conditions, 1-cis-enynyl-
      2,2-dialkyl epoxides and 1-cis-enynyl- 2-alkyl-2-aryl epoxides gave the
      corresponding 6,6-disubstituted cyclohexa-2,4-dien-1-ones in good yields (85
      91%). Mechanisms for these new cyclization reactions are proposed on the basis of
      trapping experiments and isotope labeling experiments. The formation of 1H-indene
      products likely involves ruthenium-acyl intermediates whereas cyclohexa-2,4-dien
      1-ones are thought to derive from ruthenium-ketene intermediates.

PMID- 15498000
TI  - New synthetic approach to cyclopenta-fused heterocycles based upon a mild nazarov
      reaction. 2. Further studies on the torquoselectivity.
AB  - Conjugated alkoxytrienes in which one of the double bonds is embedded in a
      heterocyclic moiety are obtained by the Pd-catalyzed coupling reaction of lactam-
      and lactone-derived vinyl triflates with alpha-alkoxydienylboronates. These
      compounds undergo a 4pi electrocyclization process (Nazarov reaction) under
      acidic conditions and afford cyclopenta-fused heterocycles in good yields. As a
      continuation of a previous study, the torquoselectivity of this Nazarov reaction
      has been investigated using 2-alkyl-substituted pyrrolidinone and 2- and 4
      substituted delta-valerolactone derivatives. High or complete stereoselectivity
      has only been observed with the 2-alkyl-substituted heterocycles. Both steric and
      stereoelectronic effects could contribute to determining the stereoselection of
      the ring closure.

PMID- 15498001
TI  - Electroreductive intramolecular coupling of aromatic beta- and gamma-imino
      esters: a new synthetic method for N-alkoxycarbonyl-2-aryl-3-ones and cis-2-aryl
      3-ols of pyrrolidines and piperidines.
AB  - The electroreduction of aromatic beta- and gamma-imino esters prepared from beta
      alanine and GABA in the presence of chlorotrimethylsilane and subsequent N
      alkoxycarbonylation of the resulting five- and six-membered cyclized amines gave
      mixed ketals of N-alkoxycarbonyl-2-arylpyrrolidin-3-ones and 2-arylpiperidin-3
      ones, respectively. The best result of the electroreductive intramolecular
      coupling was achieved using Bu(4)NClO(4) as a supporting electrolyte and a Pb
      cathode in THF. Acid hydrolysis of the mixed ketals afforded N-alkoxycarbonyl-2
      arylpyrrolidin-3-ones and 2-arylpiperidin-3-ones in good yields. The reduction of
      these ketones with NaBH(4) in methanol afforded the corresponding N
      alkoxycarbonyl-cis-2-arylpyrrolidin-3-ols and cis-2-arylpiperidin-3-ols
      diastereospecifically.

PMID- 15498002
TI  - Investigations of a novel process to the framework of benzo[c]cinnoline.
AB  - A novel synthetic process leading to the framework of benzo[c]cinnoline has been
      discovered and investigated. The process is composed of two separate reactions,
      the first of which is a partial reduction of the nitro groups of the 2,2'
      dinitrobiphenyl, a process that we believe proceeds via a SET mechanism to yield
      the hydroxyamino and nitroso groups. In the following step the cyclization takes
      place under formation of the -N=N- bond. We believe that this process take place
      via a radical mechanism through the nitroso radical anion. The novel process
      affords either benzo[c]cinnoline or benzo[c]cinnoline N-oxide, both in high
      yields, 93% and 91%, respectively. To obtain benzo[c]cinnoline, the reaction is
      conducted with an alcohol as solvent and an alkoxide as the base, while for
      benzo[c]cinnoline N-oxide, water is used as solvent with sodium hydroxide as the
      base. To establish the latter procedure, statistical experimental design and
      multivariate modeling were utilized to reveal the response surface for the
      reaction and to determine the optimal conditions for the reaction. A proposal for
      the complex reaction mechanism is given. During the corroboration of the
      mechanism, a new deoxygenation reaction for converting benzo[c]cinnoline N-oxide
      into benzo[c]cinnoline was discovered. The reaction is conducted by treating the
      N-oxide with sodium ethoxide at elevated temperature to achieve near-quantitative
      conversion into benzo[c]cinnoline in a yield of 96%.

PMID- 15498003
TI  - Novel fragmentation reaction of 2-alkyl- and 2,4-dialkyl-3-iodo-1-oxocyclohexan
      2,4-carbolactones.
AB  - 2-Alkyl- and 2,4-dialkyl-3-iodo-1-oxocyclohexan-2,4-carbolactones undergo lithium
      hydroxide- and lithium alkoxide-induced fragmentation reactions to provide
      butenolides, gamma-hydroxycyclohexenones, and/or gamma-butyrolactones. In
      general, product distribution is governed by two factors: (1) the nature of
      nucleophiles and (2) the steric bulkiness of the substituents at C-2 and C-4 of
      the cyclohexanones. Lithium hydroxide-induced fragmentation provides butenolides
      and gamma-hydroxycyclohexenones. In contrast, lithium alkoxide-promoted
      fragmentation results in predominantly 5-substituted gamma-butyrolactones along
      with a small amount of butenolides in limited cases. Fragmentation products
      induced by lithium hydroxide are largely influenced by the steric bulkiness of
      the substituents at C-2 and C-4 of the cyclohexanone ring. The bulky substituents
      render the exclusive formation of butenolides.

PMID- 15498004
TI  - Synthesis of (-)-9,10-epi-stemoamide.
AB  - An efficient synthesis of (-)-9,10-epi-stemoamide has been accomplished in nine
      steps and 13% overall yield. The synthesis features a lithium hydroxide-promoted
      fragmentation and an intramolecular 7-exo-trig radical cyclization.

PMID- 15498006
TI  - Efficient synthesis of 1,4,5,12-tetraazatriphenylene and derivatives.
AB  - Condensation of 5,6-diamino-4,7-phenanthroline with glyoxal provides 1,4,5,12
      tetraazatriphenylene in quantitative yield. This procedure avoids the 50% loss of
      product inherent in previous methods. Derivatives were also prepared by using
      alpha-dicarbonyl compounds other than glyoxal. Additional derivatives were
      prepared from 1,4,5,12-tetraazatriphenylene-2,3-dicarbonitrile, produced by
      condensation of diaminomaleonitrile with 4,7-phenanthroline-5,6-dione.

PMID- 15498005
TI  - Large cyclic peptides as cores of multivalent ligands: application to inhibitors
      of receptor binding by cholera toxin.
AB  - Large cyclic decapeptides (up to 50-atom ring) were synthesized efficiently on
      the solid phase with allyl-ester protection of the carboxyl terminus during
      elongation. Pentavalent ligands, in a "core-linker-finger" modular setup, were
      assembled by using these cyclic peptide cores to demonstrate large affinity gains
      for inhibition of surface receptor binding by the cholera toxin B pentamer. The
      results suggest that the peptide cores retain expanded conformation in solution
      so that shorter flexible linkers are needed for larger peptide cores to achieve
      the best inhibitory results.

PMID- 15498007
TI  - Solvent-free Al(OTf)3-catalyzed aminolysis of 1,2-epoxides by 2-picolylamine: a
      key step in the synthesis of ionic liquids.
AB  - Beta-Amino alcohols N-2'-pyridylmethyl substituted 3 have been prepared in
      excellent yields under mild conditions by the first Lewis acid-catalyzed
      aminolysis of 1,2-epoxides 1 with the bihaptic amine 2-picolylamine (2) with use
      of 5 mol % of Al(OTf)(3) under solvent-free conditions. As a representative of a
      new class of ionic liquids, cis-5-[(4'-methylphenyl)sulfonyl]-1,2,3,4,4a,5,6,11a
      octahydropyrido[1,2-a]quinoxalin-11-ium methanesulfonate (6) and its chloride
      derivative 7 have been synthesized under environmentally friendly conditions by
      the one-pot aminolysis of cyclohexene oxide (1a) with 2 and intramolecular
      cyclization of the resulting 2-[(pyridin-2'-yl)methylamino]cyclohexanol (3a).

PMID- 15498008
TI  - A fine-tuned molybdenum hexacarbonyl/phenol initiator for alkyne metathesis.
AB  - A new, highly potent activator for molybdenum hexacarbonyl and 2-fluorophenol is
      described. An "instant"catalyst formed in situ from molybdenum hexacarbonyl and 2
      fluorophenol shows high activity for cross- and ring-closing alkyne metathesis
      reaction. The use of 2-fluorophenol can be combined with other activation methods
      to allow alkyne metathesis at relatively low temperature (80 degrees C).

PMID- 15498009
TI  - Synthesis of disubstituted imidazo[4,5-b]pyridin-2-ones.
AB  - Regioselective palladium-catalyzed amination of 2-chloro-3-iodopyridine followed
      by a subsequent palladium-catalyzed amination leads to 2,3-diaminopyridines.
      Treatment with triphosgene affords highly functionalized unsymmetrical
      imidazo[4,5-b]pyridin-2-ones in just three synthetic steps. A two-step synthesis
      of pseudosymmetrically disubstituted imidazo[4,5-b]pyridin-2-ones, 1,4
      disubstituted pyrido[2,3-b]pyrazinediones, and 1,3-disubstituted thiadiazolo[3,4
      b]pyridin-2-ones is also described.

PMID- 15498010
TI  - Microwave-assisted allylation of acetals with allyltrimethylsilane in the
      presence of CuBr.
AB  - We describe the first synthesis of homoallyl ethers from acetals and
      allyltrimethylsilane using microwave heating and CuBr as a promoter. This method
      works best for aromatic acetals, giving the corresponding homoallyl ethers in
      good to quantitative yield.

PMID- 15498011
TI  - Streamlined synthesis of per-O-acetylated sugars, glycosyl iodides, or
      thioglycosides from unprotected reducing sugars.
AB  - Solvent-free per-O-acetylation of sugars with stoichiometric acetic anhydride and
      catalytic iodine proceeds in high yield (90-99%) to give exclusively pyranose
      products as anomeric mixtures. Without workup, subsequent anomeric substitution
      employing iodine in the presence of hexamethyldisilane (i.e., TMS-I generated in
      situ) gives the corresponding glycosyl iodides in 75-95% isolated yield.
      Alternatively, and without workup, further treatment with dimethyl disulfide or
      thiol (ethanethiol or thiocresol) gives anomerically pure thioglycosides in more
      than 75% overall yield.

PMID- 15498012
TI  - Synthesis of novel KDR kinase inhibitors through catalytic reductive cyclization
      of o-nitrobenzylcarbonyl compounds.
AB  - An efficient synthesis of o-nitrobenzylcarbonyl compounds is demonstrated through
      the Swern-type oxidation of readily accessible phenethanol analogues. Reductive
      cyclization of o-nitrobenzylcarbonyl 3 using catalytic Raney nickel gives 1H
      indol-2-yl-1H-quinoline 2 in 95% yield. Hydrolysis of 2 affords the KDR kinase
      inhibitor 1 in quantitative yield. The examination of the reductive cyclization
      reaction and optimization of conditions is described.

PMID- 15498013
TI  - A concise route to (+)-lactacystin.
AB  - A facile chromatography-free route to Kang's intermediate for the synthesis of
      (+)-lactacystin, a potent proteasome inhibitor, has been developed starting with
      Brown's asymmetric crotylation of tert-butyl 5-formyl-2,2-dimethyl-1,3-dioxan-5
      ylcarbamate, easily available from 2-amino-2-(hydroxymethyl)propane-1,3-diol
      (Tris).

PMID- 15498014
TI  - Diels-Alder additions of benzynes within helicene skeletons.
AB  - Although the contortions required are unprecedented, the benzynes formed by the
      fluoride-induced elimination of TMSOTf from o-trimethylsilyl [6]- and [7]
      helicenol triflates add to another ring of the helicenes rather than to an
      external furan molecule.

PMID- 15498015
TI  - Regioselective copolymerization of acryl sucrose monomers.
AB  - 1',2,3,3',4,4',6-Hepta-O-benzyl-sucrose has been prepared and selectively 6'-O
      esterified with small alpha,beta-unsaturated acid derivatives. New chiral
      copolymers containing sucrose have been synthesized by radical polymerization,
      and some of their physical properties have been determined.

PMID- 15498016
TI  - Biological tuning of synthetic tactics in solid-phase synthesis: application to A
      beta(1-42).
AB  - The beta-amyloid(1-42) sequence has long been recognized as a challenging target
      for solid-phase peptide synthesis. We found that the known disaggregating role of
      Met-35 sulfoxide could be capitalized during stepwise solid-phase assembly of the
      A beta(1-42) peptide chain to mitigate on-resin peptide chain aggregation, a
      presumed major source of synthetic difficulties. Furthermore, we demonstrate a
      hitherto-unreported on-resin reduction of the sulfoxide "aggregation protecting
      group" to allow for standard cleavage protocols, obviating a separate solution
      phase sulfoxide reduction step.

PMID- 15498017
TI  - Ferrocenyl monophosphine ligands: synthesis and applications in the Suzuki
      Miyaura coupling of aryl chlorides.
AB  - Ferrocenyl monophosphine ligands have been developed by a method based on
      palladium-catalyzed Suzuki-Miyaura coupling. The modular procedure creates a
      rapid synthesis of phosphines with diverse properties. The electron-rich
      phosphines have been successfully applied to the Suzuki-Miyaura coupling of
      activated and deactivated aryl chlorides, with low catalyst loading being
      feasible in the synthesis of tris-ortho-substituted biaryls.

PMID- 15498018
TI  - Preparation of C-3,5-acyl furanoses via highly selective intramolecular acyl
      migration.
AB  - A practical synthesis of C-3,5-acyl furanose via a base-catalyzed, highly
      selective intramolecular acyl migration in alcohol solvents is reported.

PMID- 15498019
TI  - Asymmetric synthesis of C-aliphatic homoallylic amines and biologically important
      cyclohexenylamine analogues.
AB  - An efficient method for the asymmetric synthesis of C-aliphatic homoallylic
      amines with up to 94% yield and 80% de is reported. Ring-closing metathesis of
      several chiral homoallylic amines using the second-generation Grubbs catalyst
      provided easy access to a wide variety of cyclohexenylamines.

PMID- 15498023
TI  - Demonstration of N- and C-terminal domain intramolecular interactions in rat
      liver carnitine palmitoyltransferase 1 that determine its degree of malonyl-CoA
      sensitivity.
AB  - We have previously proposed that changes in malonyl-CoA sensitivity of rat L-CPT1
      (liver carnitine palmitoyltransferase 1) might occur through modulation of
      interactions between its cytosolic N- and C-terminal domains. By using a cross
      linking strategy based on the trypsin-resistant folded state of L-CPT1, we have
      now shown the existence of such N-C (N- and C-terminal domain) intramolecular
      interactions both in wild-type L-CPT1 expressed in Saccharomyces cerevisiae and
      in the native L-CPT1 in fed rat liver mitochondria. These N-C intramolecular
      interactions were found to be either totally (48-h starvation) or partially
      abolished (streptozotocin-induced diabetes) in mitochondria isolated from animals
      in which the enzyme displays decreased malonyl-CoA sensitivity. Moreover,
      increasing the outer membrane fluidity of fed rat liver mitochondria with benzyl
      alcohol in vitro, which induced malonyl-CoA desensitization, attenuated the N-C
      interactions. This indicates that the changes in malonyl-CoA sensitivity of L
      CPT1 observed in mitochondria from starved and diabetic rats, previously shown to
      be associated with altered membrane composition in vivo, are partly due to the
      disruption of N-C interactions. Finally, we show that mutations in the regulatory
      regions of the N-terminal domain affect the ability of the N terminus to interact
      physically with the C-terminal domain, irrespective of whether they increased
      [S24A (Ser24-->Ala)/Q30A] or abrogated (E3A) malonyl-CoA sensitivity. Moreover,
      we have identified the region immediately N-terminal to transmembrane domain 1
      (residues 40-47) as being involved in the chemical N-C cross-linking. These
      observations provide the first demonstration by a physico-chemical method that L
      CPT1 adopts different conformational states that differ in their degree of
      proximity between the cytosolic N-terminal and the C-terminal domains, and that
      this determines its degree of malonyl-CoA sensitivity depending on the
      physiological state.

PMID- 15498024
TI  - Manganese toxicity and Saccharomyces cerevisiae Mam3p, a member of the ACDP
      (ancient conserved domain protein) family.
AB  - Manganese is an essential, but potentially toxic, trace metal in biological
      systems. Overexposure to manganese is known to cause neurological deficits in
      humans, but the pathways that lead to manganese toxicity are largely unknown. We
      have employed the bakers' yeast Saccharomyces cerevisiae as a model system to
      identify genes that contribute to manganese-related damage. In a genetic screen
      for yeast manganese-resistance mutants, we identified S. cerevisiae MAM3 as a
      gene which, when deleted, would increase cellular tolerance to toxic levels of
      manganese and also increased the cell's resistance towards cobalt and zinc. By
      sequence analysis, Mam3p shares strong similarity with the mammalian ACDP
      (ancient conserved domain protein) family of polypeptides. Mutations in human
      ACDP1 have been associated with urofacial (Ochoa) syndrome. However, the
      functions of eukaryotic ACDPs remain unknown. We show here that S. cerevisiae
      MAM3 encodes an integral membrane protein of the yeast vacuole whose expression
      levels directly correlate with the degree of manganese toxicity. Surprisingly,
      Mam3p contributes to manganese toxicity without any obvious changes in vacuolar
      accumulation of metals. Furthermore, through genetic epistasis studies, we
      demonstrate that MAM3 operates independently of the well-established manganese
      trafficking pathways in yeast, involving the manganese transporters Pmr1p, Smf2p
      and Pho84p. This is the first report of a eukaryotic ACDP family protein involved
      in metal homoeostasis.

PMID- 15498025
TI  - Another biological effect of tosylphenylalanylchloromethane (TPCK): it prevents
      p47phox phosphorylation and translocation upon neutrophil stimulation.
AB  - TPCK (tosylphenylalanylchloromethane), first discovered as a serine protease
      inhibitor, has been described to affect in diverse systems a number of
      physiological events probably unrelated to its antiprotease effect, such as
      proliferation, apoptosis and tumour formation. In the present study, we focus on
      its inhibition of the neutrophil respiratory burst, an important element of non
      specific immunological defence. The superoxide anion-producing enzyme, NADPH
      oxidase, is quiescent in resting cells. Upon cell stimulation, the redox
      component, membrane-bound flavocytochrome b558, is activated when the cytosolic
      factors (p47phox, p67phox and p40phox, as well as the small GTPase Rac) associate
      with it after translocating to the membrane. This requires the phosphorylation of
      several p47phox serine residues. The signal transduction events leading to enzyme
      activation are not completely understood. In the past, the use of diverse
      protease inhibitors suggested that proteases were involved in NADPH oxidase
      activation. We suggested previously that TPCK could prevent enzyme activation by
      the phorbol ester PMA, not due to inhibition of a protease, but possibly to
      inhibition of the cytosolic factor translocation [Chollet-Przednowed and Lederer
      (1993) Eur. J. Biochem. 218, 83-93]. In the present work, we show that TPCK, when
      added to cells before PMA, prevents p47phox phosphorylation and hence its
      translocation; moreover, when PMA-stimulated cells are incubated with TPCK,
      p47phox is dephosphorylated and dissociates from the membrane. These results are
      in line with previous suggestions that the respiratory burst is the result of a
      series of continuous phosphorylation and dephosphorylation events. They suggest
      that TPCK leads indirectly to activation of a phosphatase or inactivation of a
      kinase, and provide the first clue towards understanding the steps leading to its
      inhibition of NADPH oxidase activation.

PMID- 15498026
TI  - The role of pneumolysin in pneumococcal pneumonia and meningitis.
AB  - Diseases caused by Streptococcus pneumoniae include pneumonia, septicaemia and
      meningitis. All these are associated with high morbidity and mortality. The
      pneumococcus can colonize the nasopharynx, and this can be a prelude to
      bronchopneumonia and invasion of the vasculature space. Proliferation in the
      blood can result in a breach of the blood-brain barrier and entry into the
      cerebrospinal fluid (CSF) where the bacteria cause inflammation of the meningeal
      membranes resulting in meningitis. The infected host may develop septicaemia
      and/or meningitis secondary to bronchopneumonia. Also septicaemia is a common
      precursor of meningitis. The mechanisms surrounding the sequence of infection are
      unknown, but will be dependent on the properties of both the host and bacterium.
      Treatment of these diseases with antibiotics leads to clearance of the bacteria
      from the infected tissues, but the bacteriolytic nature of antibiotics leads to
      an acute release of bacterial toxins and thus after antibiotic therapy the
      patients can be left with organ-specific deficits. One of the main toxins
      released from pneumococci is the membrane pore forming toxin pneumolysin. Here we
      review the extensive studies on the role of pneumolysin in the pathogenesis of
      pneumococcal diseases.

PMID- 15498027
TI  - Is there a role for mannan/mannose-binding lectin (MBL) in defence against
      infection following chemotherapy for cancer?

PMID- 15498028
TI  - Variable NKG2 expression in the peripheral blood lymphocytes of rhesus monkeys.
AB  - To provide a basis for beginning to explore the CD94/NKG2 family of molecules in
      rhesus monkeys, we sought to characterize the expression of these inhibitory and
      activating cell signalling molecules in peripheral blood mononuclear cells
      (PBMCs) from healthy rhesus monkeys. We developed and employed a semiquantitative
      polymerase chain reaction (PCR)-based assay to evaluate mRNA expression levels of
      nine NKG2 molecules in PBMCs from the monkeys. In addition to quantitating NKG2A,
      NKG2B, NKG2C2, NKG2C and NKG2D expression, mRNA expression of transmembrane
      deleted forms of these molecules was also evaluated. Significant variability in
      NKG2 mRNA expression in the PBMCs was detected, with 15 unique NKG2 expression
      level profiles detected in a study of 15 monkeys. We also found that the ratio of
      the expressed levels of mRNA of the four NKG2 splice variants, NKG2A, NKG2B,
      NKG2ADeltatm, and NKG2BDeltatm, was variable between the monkeys as well as in an
      individual monkey over a period of 1.5 years. These findings indicate the dynamic
      nature of NKG2 mRNA expression in the rhesus monkey.

PMID- 15498029
TI  - The lung cytokine microenvironment influences molecular events in the lymph nodes
      during Th1 and Th2 respiratory mucosal sensitization to antigen in vivo.
AB  - Originally defined by their patterns of cytokine production, Th1 and Th2 cells
      have been described more recently to express other genes differentially as well,
      at least in vitro. In this study we compared the expression of Th1- and Th2
      associated genes directly during in vivo sensitization to ovalbumin (OVA) in Th1-
      and Th2-polarized models of airways inflammation. Th1-polarized airway
      inflammation was achieved by the intranasal instillation of adenoviral vectors
      (Ad) encoding granulocyte-macrophage colony-stimulating factor (GM-CSF) and
      interleukin (IL)-12, followed by daily aerosolizations of OVA; instillation of
      Ad/GM-CSF alone with OVA aerosolization led to Th2-polarized responses. Lymph
      nodes were obtained at various time-points, RNA extracted, and analysed by real
      time quantitative polymerase chain reaction (PCR). Consistent with reports from
      in vitro and human studies, mice undergoing Th1-polarized inflammation showed
      preferential expression of the transcription factor t-bet, the chemokines IFN
      gamma inducible protein (IP)-10 and macrophage inflammatory protein 1 alpha (MIP
      1-alpha), and the chemokine receptor CCR5. In contrast, the transcription factor
      GATA-3, the chemokines I-309 and thymus and activation regulated chemokine
      (TARC), and the chemokine receptors CCR3 and CCR4 were preferentially expressed
      in the Th2 model. Importantly, we also show that Ad/transgene expression remains
      compartmentalized to the lung after intranasal instillation. Flow cytometric
      analysis of lung myeloid dendritic cells indicated that B7.1 was expressed more
      strongly in the Th1 model than in the Th2 model. These studies provide a direct
      comparison of gene expression in in vivo Th1- and Th2-polarized models, and
      demonstrate that molecular events in the lymph nodes can be altered fundamentally
      by cytokine expression at distant mucosal sites.

PMID- 15498030
TI  - Are alterations of lymphocyte subpopulations in polymicrobial sepsis and DHEA
      treatment mediated by the tumour necrosis factor (TNF)-alpha receptor (TNF-RI)? A
      study in TNF-RI (TNF-RI(-/-)) knock-out rodents.
AB  - Sepsis is associated with depression of T cell-dependent immune reactivity with
      proinflammatory cytokines, such as tumour necrosis factor (TNF)-alpha, playing an
      important role. Recent investigations describe an association between these
      immunological alterations and disturbances of the endocrine system, related most
      frequently to sex steroid hormones. Dehydroepiandrosterone (DHEA), one of the
      most abundant adrenal sex steroid precursors, seems to have a protective
      immunological effect towards septic insults. In this study, both the role of TNF
      receptor I (RI) and possible interactions in the protective role of DHEA were
      investigated in a murine model of polymicrobial sepsis. Polymicrobial sepsis was
      induced by caecal ligation and puncture (CLP) in a murine model. The effects of
      DHEA on survival, clinical parameters and cellular immunity (T lymphocytes and
      natural killer (NK) cells) were investigated. CLP was performed in genetically
      modified TNF-RI knock-out (TNF-RI(-/-)) and genetically unmodified (wild-type,
      WT) mice. DHEA application was associated with a decrease in the mortality rate
      in WT animals. A mortality rate of 91.7% was observed in TNF-RI(-/-) mice after
      CLP. This mortality rate was reduced to 37.5% by the application of DHEA. In sham
      operated TNF-RI(-/-) animals, a significantly higher proportion of NK cells
      within the lymphocyte population was measured compared with the corresponding WT
      group. After CLP, a significant increase in the percentage cell count of NK cells
      was recorded in WT mice. Overall, following DHEA application in WT mice, an
      alteration in the cellular immune response was characterized by a reduction in
      the percentage counts of CD4(+), CD8(+) and NK cells. In the group of TNF-RI(-/-)
      mice treated with DHEA, no increase in the percentage cell count of NK cells was
      observed after CLP. No data for cell analysis were available from the CLP-TNF-RI(
      /-) mice treated with saline, due to the high mortality rate in these animals.
      DHEA reduces the complications of sepsis in a TNF-RI-independent manner. Our
      study suggests that NK cells are involved in the protective mechanism of DHEA in
      WT mice. It would therefore seem that DHEA represents a feasible alternative
      therapy for the dysregulated immune system in sepsis.

PMID- 15498031
TI  - Interferon-gamma-modified dendritic cells suppress B cell function and ameliorate
      the development of experimental autoimmune myasthenia gravis.
AB  - This study was designed to investigate the therapeutic effects of interferon
      (IFN)-gamma-modulated dendritic cells (DC) in experimental autoimmune myasthenia
      gravis (EAMG). We induced EAMG in Lewis rats by immunization with Torpedo
      nicotinic acetylcholine receptor (nAChR) and adjuvant. On day 33 post
      immunization (p.i.), splenic DC were prepared, exposed to IFN-gamma alone (IFN
      gamma-DC) or to IFN-gamma in combination with 1-methyl-DL-tryptophan (1-MT), the
      specific inhibitor of indoleamine 2,3-dioxygenase (IDO) (IFN-gamma + 1-MT-DC),
      and injected subcutaneously into rats with incipient EAMG on day 5 p.i. A control
      group of EAMG rats received naive DC on day 5 p.i., while another group received
      1-MT every other day, intraperitoneally (p.i.), from days 5 to 41 p.i. The
      severity of clinical signs of EAMG was reduced dramatically in IFN-gamma-DC
      treated rats compared to rats receiving naive DC, IFN-gamma + 1-MT-DC or 1-MT
      alone. The number of plasma cells secreting nAChR antibodies was reduced and the
      expression of B cell activation factor (BAFF) on splenic and lymph node
      mononuclear cells (MNC) was down-regulated in rats treated with IFN-gamma-DC. In
      vitro co-culture of MNC derived from EAMG rats with IFN-gamma-DC produced
      relatively few cells secreting nAChR antibodies. Addition of 1-MT to the co
      culture significantly increased the number of cells secreting nAChR antibodies.
      We conclude that IFN-gamma-DC reduced the number of plasma cells secreting nAChR
      antibodies in an IDO-dependent manner and ameliorated the development of EAMG in
      Lewis rats.

PMID- 15498032
TI  - Chemical induction of HO-1 suppresses lupus nephritis by reducing local iNOS
      expression and synthesis of anti-dsDNA antibody.
AB  - There is accumulating evidence that haem oxygenase (HO)-1 plays a protective role
      in various disorders. The beneficial efficacy of HO-1 induction therapy has been
      shown in renal diseases such as glomerulonephritis, interstitial nephritis and
      drug induced nephrotoxicity. However, involvement of HO-1 in the development of
      autoimmune renal diseases remains uncertain. To assess the clinical efficacy of
      HO-1 induction therapy for lupus glomerulonephritis, MRL/lpr mice were
      intraperitoneally injected with 100 micromol/kg hemin, a potent HO-1 inducer, or
      PBS as controls, once a week from 6 weeks of age to 21-24 weeks-old. We found
      that treatment with hemin led to a significant reduction of proteinuria and
      remarkable amelioration of glomerular lesions accompanied by decreased immune
      depositions. In addition, the circulating IgG anti-double-stranded DNA antibody
      level was significantly decreased in hemin treated mice when compared with
      controls. A single intraperitoneal injection with hemin resulted in reduction of
      inducible nitric oxide synthase expression in the kidney and spleen, and serum
      interferon-gamma level. Our results suggest that HO-1 induction therapy
      ameliorates lupus nephritis by suppressing nitric oxide (NO) dependent
      inflammatory responses and attenuating production of pathogenic autoantibodies.

PMID- 15498033
TI  - Allogenic donor splenocytes pretreated with antisense peptide against B7 prolong
      cardiac allograft survival.
AB  - The interaction of T cell CD28/CTLA-4 receptors with B7 on antigen-presenting
      cells (APCs) represents an important co-stimulatory pathway in T cell activation
      or anergy. Our previous study indicated that recipients immunized with allogenic
      donor immature dendritic cells (DCs) or resting B cells could induce specific
      immune tolerance and prolong allograft survival. A possible mechanism for this
      observation is that the expression of B7 molecules is either at a low level or
      lacking on these cells. The present study investigates whether blockade of B7
      molecules on donor splenocytes with a B7 antisense peptide (B7AP), i.e. a peptide
      analogue of the CD28-binding region, could induce specific immune tolerance and
      prolong allograft survival in the recipients. Both the lymphocyte proliferation
      reaction and the mice pinna cardiac allograft experiment were performed to
      evaluate the role of B7AP in inducing specific immune tolerance in recipients in
      vitro and in vivo. The results showed that 56.65% and 20.52% of C57BL/6
      splenocytes expressed B7.1 and B7.2 molecules, respectively, on their cell
      surface. There were no significant changes of the B7 expression on such
      splenocytes after being treated by the B7AP (53.28% and 19.06%, respectively).
      B7AP inhibited the mixed lymphocyte reaction by up to 38.4% and a dose-response
      correlation was observed for inhibition. The recipients (BALB/c) immunized with
      B7AP-pretreated C57BL/6 splenocytes induced a specific immune hypo-response
      (43%versus control) and notably prolonged survival of the C57BL/6 cardiac
      allograft by up to 20.3 days. In contrast to the normal saline group (average:
      8.6 days) and FTD(10) control peptide group (<4 days), the cardiac allograft
      survival of the test group was extended for an additional 11.7 days. These
      results strongly support the notion that immunization with donor splenocytes,
      which had been pretreated with B7AP, induced specific immune tolerance and
      prolonged allograft survival in the recipients.

PMID- 15498034
TI  - Expression of Werner and Bloom syndrome genes is differentially regulated by in
      vitro HIV-1 infection of peripheral blood mononuclear cells.
AB  - In HIV infection, continuous immune activation leads to accelerated ageing of the
      adaptive immune system, similar to that observed in elderly people. We
      investigated the expression of WRN and BLM (genes involved in disorders
      characterized by premature ageing, genomic instability and cancer predisposition)
      in peripheral blood mononuclear cells (PBMC) activated in vitro with
      phytohaemagglutinin (PHA) and infected with different HIV-1 strains. The steady
      state levels of mRNA were analysed by reverse transcription-polymerase chain
      reaction (RT-PCR), and protein expression was assayed using immunocytochemistry
      and Western blot techniques. In uninfected PBMC, PHA stimulation induced an
      increase in BLM mRNA and protein expression, while WRN expression remained
      virtually unchanged. When PBMC were infected in vitro with a lymphotropic HIV-1
      strain, the level of BLM mRNA showed a peak at 24 h of infection, followed by a
      decline to uninfected culture levels. A similar result failed to be seen using an
      R5-tropic HIV-1 strain. In accordance with mRNA expression, in HIV-infected
      cultures PBMC were stained more frequently and more intensely by a BLM-specific
      antibody as compared to uninfected cultures, staining peaking at 24. Conversely,
      WRN expression was not modulated by HIV-1. The proportion of cells showing BLM up
      regulation, established by immunocytochemical staining, was much greater than the
      proportion of productively infected PBMC, as established by proviral DNA
      measurement. This result indicates that BLM up-regulation is probably a result of
      an indirect bystander cell effect. Activation of the BLM gene in infected PBMC
      suggests that premature ageing could be a further immunopathogenetic mechanism
      involved in HIV-induced immunodeficiency, and points to a possible new candidate
      target for innovative therapeutic intervention.

PMID- 15498035
TI  - Interleukin-12 up-regulates perforin- and Fas-mediated lymphokine-activated
      killer activity by intestinal intraepithelial lymphocytes.
AB  - Human intraepithelial lymphocytes (IELs) comprise a unique compartment of memory
      T cell receptor (TCR)-alphabeta( +)CD8(+) T lymphocytes interspersed between
      intestinal epithelial cells. They develop potent lymphokine-activated killer
      (LAK) activity with interleukin (IL)-15, a cytokine that is found in excess in
      certain mucosal inflammatory states. IL-12, released by activated antigen
      presenting cells, is known to potentiate perforin-induced cytotoxicity. This
      study evaluates the mechanism by which IL-12 up-regulates LAK activity. When IELs
      were stimulated with IL-15, the CD94(+) IEL subset expanded and carried out
      cytotoxic activity in redirected lysis against P815 cells as well as Fas ligand
      (FL)- and tumour necrosis factor (TNF)-alpha-mediated lysis of Jurkat and WEHI
      cells, respectively. IL-12 enhanced the perforin- and FL-, but not TNF-alpha
      mediated events. In addition, the up-regulated killing of HT-29 cells by IL-12
      was reduced by concanamycin (which targets perforin) and antibody neutralizing FL
      but not by anti-TNF-alpha antibody. Furthermore, IL-12 augmented IL-15-stimulated
      release of serine esterases as well as expression of perforin and FL by IELs, but
      not TNF-alpha. This study shows that LAK activity, carried out by the CD94(+)
      IELs, involves perforin, FL and TNF-alpha. IL-12 up-regulates the first two
      mechanisms of action, showing for the first time its effect on FL production and
      lytic activity.

PMID- 15498036
TI  - The - 564 A/G polymorphism in the promoter region of the proteinase 3 gene
      associated with Wegener's granulomatosis does not increase the promoter activity.
AB  - Proteinase 3 is the major autoantigen in patients with Wegener's granulomatosis.
      Earlier studies have shown that circulating leucocytes from patients with
      Wegener's granulomatosis show elevated proteinase 3 surface expression and mRNA
      levels. Wegener's granulomatosis patients also have increased levels of
      proteinase 3 in plasma. A single nucleotide polymorphism (SNP) (-564 A/G SNP) in
      the promoter region has been associated with disease. This SNP introduces a new
      potential Sp1 transcription factor binding site that may be responsible for the
      observed up-regulated expression of proteinase 3. To investigate this a 740 base
      pair long region of the promoter was cloned from genomic DNA. The disease
      associated -564 A/G, as well as a control -621 A/G exchange, were introduced by
      polymerase chain reaction mutagenesis and cloned into a luciferase reporter
      vector. Endogenous expression levels of proteinase 3 mRNA and promoter activity
      of the cloned constructs were measured in three myeloid cell lines, HL-60, U937
      and NB-4, and in epithelial HeLa cells. The results demonstrate a good
      correlation between the endogenous proteinase 3 mRNA expression and the promoter
      activity, as judged by luciferase activity. However, no significant differences
      in activity between the wild-type, polymorphic and the mutated control variant
      were found. In conclusion, the -564 A/G polymorphism is not responsible for the
      increased expression levels seen in myeloid cells from patients with Wegener's
      granulomatosis.

PMID- 15498037
TI  - Neutrophil responses to CRP are not dependent on polymorphism of human
      FcgammaRIIA (R131H).
AB  - IgG2a mediated in vitro phagocytosis is less effective for individuals homozygous
      for Fcgamma RIIaR131 allele and such individuals are also more susceptible to
      certain infections. It has been reported that CRP binds to Fcgamma RIIaR131 but
      not Fcgamma RIIaH131 and since Fcgamma RIIa is also a major Fc receptor on
      neutrophils it would be expected that normal healthy donors who did not have at
      least one copy of Fcgamma RIIaR131 would not respond to CRP. We examined
      responses reported to be dependent on FcgammaRIIa but no difference between
      groups was observed in CRP mediated phagocytosis of S. pneumoniae, reactive
      oxygen production, or IL-8 synthesis. This suggests that either neutrophil
      receptors other than Fcgamma RIIa are responsible for CRP mediated responses or
      differences in CRP binding to the forms of Fcgamma RIIa are comparatively minor.

PMID- 15498038
TI  - Gene expression analysis of peripheral T cells in a subgroup of common variable
      immunodeficiency shows predominance of CCR7(-) effector-memory T cells.
AB  - Common variable immunodeficiency (CVID) represents a heterogeneous group of
      antibody deficiency syndromes, characterized by defective antibody production in
      which T cell deficiency may play a pathogenic role. A subgroup of CVID patients
      has impaired in vitro T cell proliferation. Using microarray analyses of T cells
      from these patients, we found a gene expression pattern different from healthy
      controls and patients with X-linked agammaglobulinaemia. The profile of the
      differentially expressed genes suggests enhanced cytotoxic effector functions,
      antigen experienced or chronically activated T cells and a predominance of CCR7(
      ) T cells. Further experiments using flow cytometry revealed a striking
      predominance of CCR7(-) T cells in a subgroup of CVID patients, and an
      association with impaired T cell proliferation. Our observations indicate that a
      predominance of CCR7(-) T cells with effector-memory cell features and with
      reduced proliferative capacity may characterize a subgroup of CVID.

PMID- 15498039
TI  - Glycolytic enzymes associated with the cell surface of Streptococcus pneumoniae
      are antigenic in humans and elicit protective immune responses in the mouse.
AB  - Streptococcus pneumoniae is a leading cause of otitis media, sinusitis,
      pneumonia, bacteraemia and meningitis worldwide. The drawbacks associated with
      the limited number of various capsular polysaccharides that can be included in
      the polysaccharide-based vaccines focuses much attention on pneumococcal proteins
      as vaccine candidates. We extracted an enriched cell wall fraction from S.
      pneumoniae WU2. Approximately 150 soluble proteins could be identified by 2D gel
      electrophoresis. The proteins were screened by 2D-Western blotting using sera
      that were obtained longitudinally from children attending day-care centres at 18,
      30 and 42 months of age and sera from healthy adult volunteers. The proteins were
      further identified using matrix-assisted laser desorption ionization-time of
      flight mass spectrometry. Seventeen proteins were antigenic in children and
      adults, of which 13 showed an increasing antibody response with age in all eight
      children analysed. Two immunogenic proteins, fructose-bisphosphate aldolase (FBA)
      and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and a control protein with
      known low immunogenicity, heat shock protein 70 (DnaK), were expressed in
      Escherichia coli, purified and used to immunize mice. Mouse antibodies elicited
      to the recombinant (r) FBA and rGAPDH were cross-reactive with several
      genetically unrelated strains of different serotypes and conferred protection to
      respiratory challenge with virulent pneumococci. In addition, the FBA used in
      this study (NP_345117) does not have a human ortholog and warrants further
      investigation as a candidate for a pneumococcal vaccine. In conclusion, the
      immunoproteomics based approach utilized in the present study appears to be a
      suitable tool for identification of novel S. pneumoniae vaccine candidates.

PMID- 15498040
TI  - Association of increased platelet-associated immunoglobulins with
      thrombocytopenia and the severity of disease in secondary dengue virus
      infections.
AB  - Severe thrombocytopenia and increased vascular permeability are two major
      characteristics of dengue haemorrhagic fever (DHF). To develop a better
      understanding of the roles of platelet-associated IgG (PAIgG) and IgM (PAIgM) in
      inducing thrombocytopenia and its severity of disease in patients with secondary
      dengue virus infection, the relationship between the PAIgG or PAIgM levels and
      disease severity as well as thrombocytopenia was examined in 78 patients with
      acute phase secondary infection in a prospective hospital-based study. The
      decrease in platelet count during the acute phase recovered significantly during
      the convalescent phase. In contrast, the increased levels of PAIgG or PAIgM that
      occurred during the acute phase of these patients decreased significantly during
      the convalescent phase. An inverse correlation between platelet count and PAIgG
      or PAIgM levels was found in these patients. Anti-dengue virus IgG and IgM
      activity was found in platelet eluates from 10 patients in an acute phase of
      secondary infection. Increased levels of PAIgG or PAIgM were significantly higher
      in DHF than those in dengue fever (DF). An increased level of PAIgM was
      associated independently with the development of DHF, representing a possible
      predictor of DHF with a high specificity. Our present data suggest that platelet
      associated immunoglobulins involving antidengue virus activity play a pivotal
      role in the induction of thrombocytopenia and the severity of the disease in
      secondary dengue virus infections.

PMID- 15498041
TI  - Mannan-binding lectin modulates the response to HSV-2 infection.
AB  - Viruses have developed numerous strategies to escape recognition by the immune
      system. However, some viruses such as herpes simplex virus-2 (HSV-2) are
      recognized by initiators of the complement system, e.g. mannan-binding lectin
      (MBL). To study the effects of MBL deficiency during viral infection we have
      chosen a model of generalized HSV-2 infection. We infected MBL-A and MBL-C double
      knock-out mice (DKO) with HSV-2 via the intraperitoneal (i.p.) route. DKO mice
      cleared HSV-2 from the liver less efficiently than the comparable wild-type
      animals. The impairment to effectively neutralize HSV-2 correlated with
      compromised liver function as measured by increased plasma levels of alanine
      amino transferase. No differences in the viral burden were found in other organs
      such as spleen or brain. Thus, MBL-mediated protection was limited to the effects
      of preservation of liver homeostasis. Reconstitution with recombinant human MBL
      before and during the HSV-2 infection dramatically lowered the viral titres in
      the liver. Taken together, the data show that MBL modulates the response to HSV-2
      in mice by affecting neutralization of the virus. To analyse if MBL plays a role
      in establishment and progression of human HSV-2 infection we analysed MBL levels
      in the serum samples from asymptomatic (virus-exposed people who have never
      displayed symptoms of HSV-2 infection) and symptomatic HSV-2 patients (people
      with recurrent HSV-2 infections). We found that the frequency of the MBL
      deficiency (<100 ng/ml) was higher in the symptomatic group and significantly
      different from that in the asymptomatic group (P = 0.0369). This suggests that
      lack of MBL-mediated complement activation increases susceptibility to viral
      infection.

PMID- 15498042
TI  - The common heat shock protein receptor CD91 is up-regulated on monocytes of
      advanced melanoma slow progressors.
AB  - Despite advances in our understanding of tumour immunology there is no therapy of
      proven survival benefit for advanced melanoma. Nevertheless, disease progression
      is slow in a small proportion of patients with metastatic melanoma, suggesting a
      contribution to outcome from host factors. Recent data have indicated the
      importance of the heat shock protein receptor CD91 in immune responses to, and
      progression of, infectious disease. Here we investigate the relationship between
      CD91 expression and outcome in malignancy. Rare melanoma patients were recruited
      with advanced disease that was progressing unusually slowly. CD91 expression on
      their monocytes was compared with control patients with more typical rapidly
      advancing metastatic disease. Th1 and Th2 cytokines, as well as innate and
      adaptive immune subsets, were also measured in the two groups. A significant
      increase in median CD91 expression levels was observed in slow progressors (P =
      0.006). There were no differences in other immune subset markers or inflammatory
      cytokines. The ability of CD91 to internalize and cross-present tumour antigens
      through the major histocompatibility complex class I pathway may maintain CD8
      positive cytotoxic T cell responses and contribute to slow progression of
      advanced melanoma.

PMID- 15498043
TI  - Antioxidant supplementation and nasal inflammatory responses among young
      asthmatics exposed to high levels of ozone.
AB  - The inflammatory response to ozone in atopic asthma suggests that soluble
      mediators of inflammation are released in response to oxidant stress.
      Antioxidants may alleviate additional oxidative stress associated with
      photochemical oxidant pollution. This study investigates the impact of
      antioxidant supplementation on the nasal inflammatory response to ozone exposure
      in atopic asthmatic children. We conducted a randomized trial using a double
      blinded design. Children with asthma (n = 117), residents of Mexico City, were
      given randomly a daily supplement of vitamins (50 mg/day of vitamin E and 250
      mg/day of vitamin C) or placebo. Nasal lavages were performed three times during
      the 4-month follow-up and analysed for content of interleukin-6 (IL-6), IL-8,
      uric acid and glutathione (GSx). IL-6 levels in the nasal lavage were increased
      significantly in the placebo group after ozone exposure while no increase was
      observed in the supplement group. The difference in response to ozone exposure
      between the two groups was significant (P = 0.02). Results were similar for IL-8,
      but with no significant difference between the groups (P = 0.12). GSx decreased
      significantly in both groups. Uric acid decreased slightly in the placebo group.
      Our data suggest that vitamin C and E supplementation above the minimum dietary
      requirement in asthmatic children with a low intake of vitamin E might provide
      some protection against the nasal acute inflammatory response to ozone.

PMID- 15498044
TI  - Imbalance between interleukin-1 agonists and antagonists: relationship to
      severity of inflammatory bowel disease.
AB  - Interleukin (IL)-1 is a key mediator in the pathogenesis of inflammatory bowel
      disease (IBD). Naturally occurring IL-1 modulators include IL-1 receptor
      antagonist (IL-1Ra), IL-1 soluble receptor Type I (IL-1sRI), IL-1sRII and IL-1
      receptor accessory protein (AcP). Systemic and mucosal levels of IL-1 soluble
      receptors remain unknown in IBD. Plasma or colonic tissues were obtained from 185
      consecutive unselected patients with Crohn's disease (CD) or ulcerative colitis
      (UC) and from 52 control subjects. Plasma and colonic explant culture
      supernatants were assessed for IL-1alpha, IL-1beta, IL-1Ra, IL-1sRI and IL-1sRII.
      Plasma IL-1Ra levels were higher in UC (+93%) than in healthy subjects. IL-1alpha
      and IL-1beta were not detected. IL-1sRII levels were marginally lower in CD (
      10%) and UC (-9%), whereas IL-1sRI levels were elevated in CD (+28%) only. Plasma
      IL-1sRI levels correlated positively (P < 0.01) with Crohn's disease activity
      index (r = 0.53), C-reactive protein (r = 0.46) and alpha1-acid glycoprotein (r =
      0.42). In colonic explant cultures, IL-1alpha and IL-1Ra levels were elevated in
      non-lesional (+233% and +185% respectively) and lesional CD (+353% and +1069%),
      lesional UC (+604% and +1138%), but not in non-lesional UC. IL-1beta was elevated
      in lesional UC (+152%) and CD (+128%). In contrast, IL-1sRII levels were elevated
      in non-lesional CD (+65%), but remained unchanged in lesional CD, non-lesional
      and lesional UC. IL-1sRI levels did not differ between patient and control
      groups. These results indicate that (i) the proinflammatory moiety IL-1sRI is a
      systemic marker of inflammation and activity in CD and (ii) local shedding of the
      functional antagonist IL-1sRII may dampen colonic inflammation in CD, but not in
      UC.

PMID- 15498045
TI  - No evidence for apoptosis of decidual leucocytes in normal and molar pregnancy:
      implications for immune privilege.
AB  - Complete hydatidiform moles are totally paternally derived and represent complete
      allografts that might be expected to provoke maternal immune rejection. Our
      previous and other studies have shown expression of Fas by increased numbers of
      activated decidual CD4(+) T cells in both complete and partial molar pregnancy as
      well as increased FasL(+) expression by molar trophoblasts compared with
      trophoblasts in normal pregnancies. As the Fas/FasL system represents a major
      apoptotic pathway that can play a role in immune privilege, the aim of this study
      was to investigate whether apoptosis of decidual immune cells, particularly T
      cells, could be responsible for maternal immune tolerance in molar pregnancy.
      Using terminal deoxynucleotidyl transferase (TdT)-mediated nick end-labelling
      (TUNEL), a significant increase in TUNEL(+) cells was demonstrated in decidua
      associated with partial (P = 0.0052) and complete (P = 0.0096) hydatidiform mole
      compared with normal early pregnancy. Co-labelling immunoperoxidase studies
      showed that the TUNEL(+) cells in both normal and molar pregnancies were not
      activated CD45RO(+) immune cells, CD3(+) T cells, CD56(+) uterine natural killer
      (NK) cells or CD14(+) CD68(+) macrophages. Double immunohistochemical labelling
      with antiactive caspase-3 and leucocyte markers confirmed the lack of leucocyte
      apoptosis. Double immunostaining with anticytokeratin to detect trophoblast and
      M30 CytoDeath, which detects a neoepitope of cytokeratin 18 revealed after
      caspase-mediated cleavage, revealed apoptotic extravillous trophoblast cells
      within decidual tissue. We conclude that there is no evidence that apoptosis of
      decidual leucocytes plays a role in maintaining maternal tolerance in either
      normal or molar pregnancy.

PMID- 15498046
TI  - Multiplicity of the antibody response to GAD65 in Type I diabetes.
AB  - Type I diabetes (TID) is an autoimmune disease characterized in part by the
      presence of autoantibodies directed against glutamic acid decarboxylase 65
      (GAD65), among other pancreatic islet antigens. We investigated the independent
      epitope specificities of these GAD65 antibodies (GAD65Ab) and their combinations
      in the sera of new onset TID patients and first-degree relatives positive for
      GAD65Ab. For our analysis, we used four GAD65-specific recombinant Fabs (rFabs)
      that recognize different conformational determinants of GAD65 located throughout
      the molecule, including the N-terminal, the middle and the C-terminal regions. We
      used these epitope-specific rFabs in competition assays to determine the binding
      specificity of the autoantibodies found in patient sera. Among the 61 sera from
      newly diagnosed GAD65Ab-positive TID patients GAD65 binding was competed for 23
      sera by all four rFabs, 29 by at least two rFabs, and in nine sera were displaced
      by one or no rFab. In contrast, none of the 24 sera from GAD65Ab-positive first
      degree relatives of TID patients were displaced by all four rFabs. When using all
      four rFabs simultaneously to compete with GAD65Ab binding, binding of sera from
      TID patients was reduced by an average of 70%. A significantly weaker competition
      was observed when evaluating sera of GAD65Ab-positive first-degree relatives (P <
      0.0001).

PMID- 15498047
TI  - Increased CCR4 expression on circulating CD4(+) T cells in ankylosing
      spondylitis, rheumatoid arthritis and systemic lupus erythematosus.
AB  - Previous studies have suggested that CCR4 is particularly important in the
      selective recruitment of various subsets of leucocytes in rheumatoid arthritis
      (RA) and systemic lupus erythematosus (SLE). In this study, we examined the
      percentage of CD4(+)/CCR4(+) T cells within circulating lymphocytes in active
      ankylosing spondylitis (AS), RA and SLE patients. The clinical significance of
      CCR4 expression as well as possible associations between the expression and serum
      levels of tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma and
      interleukin (IL)-10 were also examined. Our results showed that the percentage of
      CD4(+)/CCR4(+) T cells was significantly elevated in AS and RA patients as
      compared with normal controls. The percentage was also significantly higher in
      SLE patients who had received no treatment with glucocorticoids or cytotoxic
      drugs (untreated SLE) than that in controls. In addition, the percentage of
      CD4(+)/CCR4(+) T cells showed significant positive correlations with the Bath
      ankylosing spondylitis disease activity index (BASDAI) in AS and with the SLE
      disease activity index (SLEDAI) in untreated SLE. Of all the cytokines examined,
      the elevated serum IL-10 level was closely correlated with the percentage of
      CD4(+)/CCR4(+) T cells in AS, RA and untreated SLE. These results suggest that
      CCR4 may be crucial in the pathogenesis of AS, RA and SLE. The percentage of
      CD4(+)/CCR4(+) T cells can serve as a useful marker for the activity of AS and
      untreated SLE.

PMID- 15498048
TI  - Interleukin (IL)-10, IL-1ra and IL-12 profiles in active and quiescent systemic
      lupus erythematosus: could longitudinal studies reveal patient subgroups of
      differing pathology?
AB  - Several cytokines have been implicated individually in the pathogenesis of
      systemic lupus erythematosus (SLE) and some, including interleukin (IL)-10, IL-12
      and IL-1ra are raised during flares of disease activity. Few studies have been
      directed at examining the interactions between these cytokines and how their
      combined profile relates to disease activity. We have examined serum levels of IL
      10, IL-12 and IL-1ra in a cohort of SLE patients obtained from the Queen
      Elizabeth Hospital, Birmingham in cross-sectional and, in a smaller group,
      longitudinal analyses. In the cross-sectional study, there were significant
      correlations between levels of the three cytokines. There were also significant
      correlations between levels of each cytokine and measures of disease activity. IL
      10 levels correlated with ESR, anti-dsDNA antibody titres and C3D, IL-12 levels
      with anti-dsDNA antibody titres and IL-1ra levels with ESR, anti-dsDNA antibody
      titres and C3D. IL-1ra levels also correlated with CRP. Circulating IL-10 and IL
      1ra levels were higher in patients with SLE than in normal controls, although in
      this study group they did not reach significance. Circulating IL-12 levels were,
      however, significantly higher in SLE compared to controls. This was true both in
      patients with active disease and those sampled during a quiescent phase. These
      data add to the evidence that cytokines such as IL-10, IL-12 and IL-1ra are
      important in SLE pathogenesis. In a retrospective study of serial serum samples
      from seven patients, we found two patients whose cytokine profile was very
      different from the rest of the group. In most patients normalized IL-10, IL-12
      and IL-1ra levels mirrored BILAG scores closely, but in these two patients, IL
      10, IL-12 and IL-1ra levels did not fluctuate with disease activity. It is
      possible that there is a subgroup of SLE patients whose cytokine profile could be
      an important indicator of their pathology. In order to confirm this and determine
      the frequency of such patients this study needs to be repeated with a much larger
      subject group. The coexistence of patient groups with different patterns of
      cytokine activity might explain conflicting reports of associations of levels of
      particular cytokines with SLE. As the observed differences could reflect
      different aetiologies of SLE, this information could reveal valuable
      endophenotypes for genetic and functional studies of SLE and might, ultimately,
      inform therapeutic management.

PMID- 15498049
TI  - Autoantibody against matrix metalloproteinase-3 in patients with systemic
      sclerosis.
AB  - Systemic sclerosis (SSc) is characterized by multi-organ fibrosis with an
      autoimmune background. Although autoantibodies are detected frequently in SSc
      patients, the role of autoantibody in the development of fibrosis remains
      unknown. Connective tissue homeostasis is a balance between the synthesis and
      degradation of the extracellular matrix (ECM); ECM degradation is regulated
      mainly by matrix metalloproteinases (MMPs). Anti-MMP-1 antibody is suggested to
      inhibit MMP-1 and be involved in the development of the fibrosis in SSc. However,
      the accumulation of various ECM components in the tissue of SSc cannot be
      explained by the anti-MMP-1 antibody alone. In this study, we examined the
      presence or levels of antibody to MMP-3, a protein which degrades various ECM
      components relevant to SSc fibrosis. Enzyme-linked immunosorbent assay (ELISA)
      using human recombinant MMP-3 revealed that IgG anti-MMP-3 autoantibody levels
      were elevated significantly in the sera from SSc patients, but not in patients
      with active systemic lupus erythematosus or dermatomyositis. IgG and IgM anti-MMP
      3 antibody levels were significantly higher in diffuse cutaneous SSc, a severe
      form, than those in limited cutaneous SSc. Consistently, IgG anti-MMP-3 antibody
      levels correlated significantly with fibrosis of the skin, lung and renal blood
      vessels. The presence of IgG anti-MMP-3 autoantibody in sera from SSc patients
      was confirmed by immunoblotting analysis. Remarkably, MMP-3 activity was
      inhibited by IgG anti-MMP-3 antibody. These results suggest that anti-MMP-3
      antibody is a serological marker that reflects the severity of SSc and also
      suggest that it may contribute to the development of fibrosis by inhibiting MMP-3
      activity and reducing the ECM turnover.

PMID- 15498050
TI  - Circulating monocytes in patients with acute coronary syndromes lack sufficient
      interleukin-10 production after lipopolysaccharide stimulation.
AB  - Acute coronary syndromes (ACS) are associated with inflammation resulting from
      monocyte activation. We sought for differences in the production of pro- and anti
      inflammatory cytokines by monocytes from patients with ACS. C-reactive protein
      (CRP) and neopterin were measured in 22 patients with acute coronary syndromes,
      50 patients with stable vascular disease and 22 healthy controls. Production of
      tumour necrosis factor (TNF)-alpha and interleukin (IL)-10 was determined after,
      respectively, 6 and 24 h of incubation of full blood with lipopolysaccharide
      (LPS). Levels of CRP [median, interquartile range (IQR)][1.5 mg/l (0.8-4.5) ACS
      patient versus 2.1 (0.9-3.6) stable disease versus 0.4 (0.3-1.2) healthy
      controls] (P < 0.001) and neopterin [7.4 nmol/l (6.0-8.7) ACS patient versus
      7.1(6.0-8.9) stable disease versus 6.4 (5.6-7.3) healthy controls] (P = 0.07)
      were higher in both the patient groups. IL-10 production after LPS stimulation
      was greatly reduced in patients with acute coronary syndromes (16 175 pg/ml, 7559
      28 470 pg/ml) as opposed to patients with stable disease (28 379 pg/ml, 12 601-73
      968 pg/ml) and healthy controls (63 830 pg/ml, 22 040-168 000 pg/ml) (P = 0.003).
      TNF-alpha production was not signi fi cantly different between the groups [7313
      pg/ml (4740-12 615) ACS patient versus 11 002 (5913-14 190) stable disease versus
      8229 (5225-11 364) healthy controls] (P = 0.24). Circulating monocytes in
      unstable coronary syndromes produce equal amounts of TNF-alpha but less IL-10
      after stimulation with LPS in vitro as compared with healthy controls. We
      hypothesize that, in acute coronary syndromes, the production proinflammatory
      cytokines is not counterbalanced by anti-inflammatory cytokines such as IL-10.

PMID- 15498052
TI  - Understanding neurochemical changes during retinal diseases.

PMID- 15498051
TI  - Cytokine mRNA repertoire of peripheral blood mononuclear cells in Takayasu's
      arteritis.
AB  - We have investigated constitutive and phytohaemagglutinin (PHA) + phorbol 12
      myristate 13-acetate (PMA)-induced gene expression of tumour necrosis factor
      (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-2, IL-3, IL-4, IL-10, IL-12
      and granulocyte macrophage colony-stimulating factor (GM-CSF) in peripheral blood
      mononuclear cells (PBMCs) of 10 patients with Takayasu's arteritis (TA) and 10
      healthy controls by semiquantitative reverse transcriptase polymerase chain
      reaction (RT-PCR). The constitutive mRNA expression of TNF-alpha (69.0 +/-
      4.0%versus 27.5 +/- 18.0%; P = 0.001) and IL-4 (60.0 +/- 10.0%versus 0%; P =
      0.001) was significantly higher in patients than controls; that of IL-3 was
      comparable in both groups (38.0 +/- 6.0%versus 32.0 +/- 5.0%; P = 0.651) while no
      constitutive mRNA expression was observed for the other cytokines studied. The
      stimulated PBMCs of patients, as compared with the controls, had higher mRNA gene
      expression of TNF-alpha (127.0 +/- 16.0%versus 54.0 +/- 6.0%; P = 0.001), IFN
      gamma (93.0 +/- 13.0%versus 57.0 +/- 5.0%; P = 0.032), IL-2 (109.0 +/-
      13.0%versus 68.0 +/- 6.0%; P = 0.015), IL-3 (60.0 +/- 8.0%versus 21.2 +/- 3.0%; P
      = 0.045) and IL-4 (68.0 +/- 7.0%versus 27.0 +/- 7.2%; P = 0.01) The mRNA
      expression of IL-10 was lower in patients than controls (35.0 +/- 8.0%versus 75.0
      +/- 12.0%; P = 0.022). The GM-CSF mRNA was similar (102.0 +/- 6.0%versus 89.0 +/-
      5.0%; P = 0.475) in both groups. Stimulation of cells with PHA + PMA showed no IL
      12 expression but stimulation with lipopolysaccharide induced higher IL-12 mRNA
      in patients than controls (83.0 +/- 14.0%versus 33.0 +/- 4.0%; P = 0.005). Our
      data suggest that an inflammatory cytokine signature exists in TA with a key role
      for TNF-alpha, IL-4, IL-10 and IL-12 in different pathological processes of the
      disease.

PMID- 15498054
TI  - An adjustable medial orbital wall suture for third nerve palsy.
AB  - A 16-year-old girl presented with a large-angle exotropia due to congenital third
      nerve palsy. She had undergone recession/resection surgery as a child. A nasal
      transposition of the superior oblique and the lateral rectus produced some
      improvement but the result was still cosmetically unacceptable. Subsequent
      surgery to permanently secure the globe to the medial orbital wall using an
      intraoperatively adjustable nonabsorbable traction suture produced a satisfactory
      outcome.

PMID- 15498055
TI  - Comparative study on the safety and efficacy of different cycloplegic agents in
      children with darkly pigmented irides.
AB  - BACKGROUND: The ideal cycloplegic drug that is safe, effective and convenient in
      children is not yet available. This study aimed to evaluate the safety and
      efficacy of three cycloplegic regimens in hyperopic children with pigmented
      irides. The responses to cycloplegia in different age groups and presence of
      strabismus were also compared. METHODS: Tropicamide 0.5% and phenylephrine 0.5%
      (regimen I), tropicamide 1.0% and cyclopentolate 1.0% (regimen II), and atropine
      1.0% (regimen III) were evaluated in 25 children using a crossover study design.
      Cycloplegic refractions were assessed. RESULTS: The mean age of the children was
      5.7 +/- 2.0 years (range 2.5-10.8 years). Six (24.0%) of them had strabismus. The
      spherical equivalent (SE) refraction for regimens I, II and III were +5.11 +/-
      2.04 D, +5.29 +/- 1.89 D and +5.71 +/- 1.90 D, respectively, and were significant
      different from the manifest SE (+3.95 +/- 2.17 D) (P < 0.001). There was no
      statistical difference between regimen I and II in children without strabismus (P
      = 0.258) or aged older than 5 years (P > 0.050). CONCLUSION: In older children,
      regimen I was as effective as regimen II and can be used to avoid cyclopentolate
      toxicity.

PMID- 15498056
TI  - Paediatric uveitis: a Sydney clinic experience.
AB  - PURPOSE: The aim of this study was to retrospectively review uveitis cases at The
      Children's Hospital at Westmead, Sydney, since its inception in 1997 to 2001,
      including patients presenting at the Camperdown, Sydney, campus between 1989 and
      1997 attending Westmead for further care. Comparison is made with international
      centres. METHODS: Information was obtained from medical records. RESULTS: Forty
      patients (53 eyes) presented, of whom 23 (57.5%) were female and 17 (42.5%) were
      male (mean age 6.7 years). Of 53 eyes, 35 (66%) had anterior uveitis, three
      (5.7%) intermediate uveitis, seven (13.2%) posterior uveitis and eight (15.1%)
      panuveitis. Twenty-seven (67.5%) patients had disease unilaterally and 13 (32.5%)
      bilaterally. Twenty-four (60%) cases were idiopathic. Seven (17.5%) cases were
      associated with juvenile rheumatoid arthritis, three (7.5%) with herpes zoster,
      two (5%) with herpes simplex, two (5%) with toxocara, one (2.5%) with toxoplasma,
      and one (2.5%) with ulcerative colitis. Complications included cataract in 14
      (26.4%) eyes; band keratopathy in four (7.5%) eyes; macular scarring in three
      (5.7%) eyes; and glaucoma in four (7.5%) eyes. Last measured acuity was 6/6 for
      19 (35.8%) eyes, < or =6/18 for 15 (28.3%) eyes and <6/60 for eight (15.1%) eyes.
      CONCLUSIONS: Despite small numbers, the comparisons of this study with some
      international studies, and its contrasts with other studies, are due to
      similarities and differences amongst these studies with respect to factors of
      referral bias, and the aetiological basis of disease.

PMID- 15498057
TI  - Autologous platelets for macular hole surgery: the Sussex Eye Hospital
      experience.
AB  - PURPOSE: To evaluate the anatomical and visual outcomes of patients managed by
      macular hole surgery with adjunctive use of autologous platelets at Sussex Eye
      Hospital, UK. METHODS: A retrospective non-comparative consecutive interventional
      case series was conducted. Standard macular hole vitrectomy surgery was combined
      with autologous platelets. No other adjuncts were used, nor internal limiting
      membrane peeling performed. The main outcome measure was anatomical closure of
      the macular hole. Secondary outcome measures included: visual outcome (best
      postoperative best corrected visual acuity [BCVA] and final BCVA), hole reopening
      and/or re-operation, complications, and time to and influence of cataract
      surgery. RESULTS: Seventy eyes of 65 patients underwent macular hole surgery with
      vitrectomy and autologous platelets. There were 14 stage 2 holes, 52 stage 3
      holes and four stage 4 holes. Mean follow up was 29 months (range 1.5-78 months).
      Primary anatomical success (hole closure) was 95.7% (n = 67); however, six (8.5%)
      holes reopened at a mean of 12.7 months (range 3.6-36.3 months) after their
      initial surgery. Final surgical success was 98.5% (65/66) in those eyes of
      patients electing re-operation procedures. Seventy-seven per cent (n = 54) of
      patients obtained 2 or more lines of visual acuity improvement at final follow up
      with a mean improvement of 4 lines (range -3 to +12 lines). Forty per cent (n =
      28) achieved final BCVA of 6/12 or better, which improved to 51% (n = 36) if best
      postoperative BCVA was considered. CONCLUSIONS: Adjunctive use of autologous
      platelets at the time of macular hole surgery yields good surgical and visual
      results, without significant complications, and should remain a considered option
      in the surgical management of macular holes. Improved macular hole closure with
      autologous platelets (compared with vitrectomy alone) has previously been
      demonstrated in a randomized controlled trial. Visual outcome benefit of
      platelets remains to be investigated by randomized controlled trial and any
      planned trials should include an autologous platelets intervention arm along with
      visual acuity as a primary outcome measure.

PMID- 15498058
TI  - Bacterial keratitis in Christchurch, New Zealand, 1997-2001.
AB  - PURPOSE: To identify which organisms cause bacterial keratitis in a local
      community and to determine how patients with suspected bacterial keratitis should
      be initially treated. METHODS: The results of all corneal scrapes performed in
      the ophthalmology department of Christchurch Hospital between 1997 and 2001 were
      reviewed. All samples were collected at the 'bedside' by a technician from the
      microbiology department and were processed immediately. RESULTS: Eighty-seven
      corneal scrapes were performed on 78 patients. There was a positive Gram stain in
      43.7% (38/87) of scrapes. There was a positive culture in 58.6% (51/87) of
      scrapes. The commonest Gram-positive organisms were coagulase negative
      Staphylococci (19.4%) and Corynebacterium spp. (16.1%). The commonest Gram
      negative organisms were Moraxella spp. (19.4%) and Pseudomonas aeruginosa (3.2%).
      Every Gram-positive organism was sensitive to chloramphenicol and every Gram
      negative organism was sensitive to ciprofloxacin. In contrast, 89% of Gram
      negative organisms were sensitive to chloramphenicol and 88% of Gram-positive
      organisms were sensitive to ciprofloxacin. CONCLUSION: The results are very
      different to those reported by other centres. Most notably, a much higher
      incidence of infection by Corynebacterium spp. and Moraxella spp. and a lower
      incidence of Pseudomonas aeruginosa was found. In this centre it appears
      appropriate to initially treat patients with Gram-positive organisms with
      chloramphenicol and patients with Gram-negative organisms with ciprofloxacin.
      Patients with a negative Gram stain should be treated with alternating
      chloramphenicol and ciprofloxacin while awaiting culture results.

PMID- 15498059
TI  - Public versus private patient priorities and satisfaction in cataract surgery.
AB  - BACKGROUND: Despite strong stereotypes of differences, few studies have compared
      private and public patient priorities and satisfaction, and none in the context
      of cataract surgery. The objective of this study was to compare samples of
      private and public patients undergoing day-stay cataract surgery. METHODS: Forty
      two public patients and 39 private patients were asked to rate the importance of
      13 domains that prior research has shown to influence patient satisfaction.
      Patients were also asked about their waiting time, amount of information they
      received, and current and expected VF-14 functional ability. One month after
      surgery, patients recorded their satisfaction with each of the 13 domains.
      RESULTS: Public patients waited ninefold longer for surgery and had lower
      preoperative visual function. Nonetheless both groups expected, and achieved, the
      same level of postoperative outcome. Although 90% of private patients were
      satisfied with the information they received regarding the surgery, 45% of public
      patients wanted more. There were significant differences in priorities between
      private and public patients. After surgery, public patients were less satisfied
      than private patients, although when accounting for the importance as well as
      satisfaction of each factor, the level of satisfaction between groups was not
      different. CONCLUSIONS: The dearth of information received by public patients
      raises important questions whether their surgery decision was sufficiently
      individualized or adequately consented. Patient satisfaction is an important
      health outcome, and understanding both the domains of satisfaction, as well as
      their relative importance to patients, is necessary to improve the overall
      quality of patient care.

PMID- 15498060
TI  - Effect of volume used in sub-Tenon's anaesthesia on efficacy and intraocular
      pressure: a randomized clinical trial of 3 mL versus 5 mL.
AB  - PURPOSE: To compare the effect of volume used in sub-Tenon's anaesthesia on
      efficacy and intraocular pressure (IOP). METHODS: A prospective, randomised
      clinical trial was conducted on 52 eyes of 52 consecutive patients undergoing sub
      Tenon's anaesthetic for cataract surgery. Eyes were randomly assigned to either 3
      mL or 5 mL volume of anaesthetic solution (0.5% bupivacaine/2% lidocaine in a
      50:50 mixture). The main outcome measures were akinesia 5 min post-administration
      of anaesthetic, changes in IOP immediately after and 5 min after anaesthetic
      administration, and patient pain perception during procedure. RESULTS: The level
      of kinesia was greater in the 3 mL group (n = 25) compared to the 5 mL group (n =
      27) (P = 0.001, Mann-;Whitney U-test). There was no significant difference in
      pain perception between the two groups (P = 0.464, student t-test). Although
      there was great variation in IOP changes following sub-Tenon's anaesthetic, there
      was a trend for a larger rise in mean IOP immediately after anaesthetic
      administration in the 5 mL group (mean +/- SD +5.6 +/- 4.2 mmHg) compared to the
      3 mL group (+4.3 +/- 3.8 mmHg), but this did not reach statistical significance
      (P = 0.25, student t-test). CONCLUSIONS: A 5 mL volume of anaesthetic provides
      akinesia superior to a 3 mL volume in sub-Tenon's anaesthesia for cataract
      surgery.

PMID- 15498061
TI  - Calcification of intraocular hydrogel lens: evidence of dystrophic calcification.
AB  - PURPOSE: To report and describe the surface calcification of three cases of
      implanted intraocular hydrogel lens. METHODS: Three surgically extracted hydrogel
      intraocular lenses were studied by light and transmission electron microscopy as
      well as by energy dispersion X-ray microanalysis. RESULTS: The lens surfaces were
      covered by granular deposits of calcium phosphate, clearly delineated by von
      Kossa and alizarin stains for calcium. Transmission electron microscopy showed
      the deposits to be located within the superficial lens material to a depth of 7
      microm and to be associated with what appear to be traces of cellular material
      including basement membrane and plasmalemma. To the authors' knowledge there has
      been only one other transmission electron microscopic study. Energy dispersion X
      ray microanalysis showed the deposits to contain calcium and phosphorous in all
      cases. CONCLUSIONS: This study confirms and extends the previous reports of five
      cases of calcification of hydrogel intraocular lenses. The exact mechanism of
      calcification remains obscure but evidence suggesting cell-mediated dystrophic
      calcification of the lens surface is presented. Further study is required to
      monitor the incidence and development of this phenomenon.

PMID- 15498062
TI  - Amniotic membrane grafting in the surgical management of primary pterygium.
AB  - BACKGROUND: To evaluate the efficacy of amniotic membrane transplantation in
      primary pterygium surgery. METHODS: Patients presenting to the outpatient clinic
      of the Royal Victorian Eye and Ear Hospital with primary pterygium requiring
      surgical management were included in this study. The pterygia were excised to
      bare sclera and the conjunctival defects were closed with amniotic membrane
      grafts. The primary outcome was pterygium recurrence. RESULTS: Twenty-eight
      pterygia of 26 patients were included. Twenty-three patients (88%, 25 eyes)
      completed 12 months follow up. By 12 months postoperatively 16 of these eyes
      (64%) had developed corneal recurrence and a further two had developed a limbal
      recurrence (9%). Five required repeat surgery during the 12 month follow-up
      period. No association was found between pterygium recurrence and pterygium size
      (P = 0.33), amniotic membrane graft dimension (P = 0.12), patient age (P = 0.53)
      or patient sex (P = 0.63). CONCLUSION: Amniotic membrane grafting for primary
      pterygium was associated with an unacceptably high recurrence rate in this
      population.

PMID- 15498064
TI  - Analysis of optineurin (OPTN) gene mutations in subjects with and without
      glaucoma: the Blue Mountains Eye Study.
AB  - BACKGROUND: The optineurin (OPTN) gene has been reported to possess both causal
      as well as risk-associated alleles for open-angle glaucoma. However, these
      findings have so far only been reported in family and clinic based studies. The
      aim of this study was to investigate the spectrum of mutations and gene variants
      in OPTN that might be present in people with glaucoma from a population-based
      study, the Blue Mountains Eye Study (BMES). METHODS: A total of 108 subjects of
      Caucasian origin were identified at baseline in the BMES as having open-angle
      glaucoma. Blood samples were available from 27 of these, of whom 18 had high
      tension glaucoma and the remaining nine had normal-tension glaucoma. Ninety-four
      control subjects were chosen at random from the BMES, who satisfied the criteria
      of not having glaucoma at baseline and were over age 70 years. The 13 coding
      exons (exons 4-16 inclusive) and their intron-exon boundaries of OPTN were
      screened by the use of single-strand conformation polymorphism. Samples
      exhibiting mobility shifts were di-deoxy nucleotide sequenced. The M98K
      polymorphism was additionally screened using the restriction enzyme Stu1 in all
      cases and controls in this study. RESULTS: The M98K risk-associated alteration
      was identified in 2/18 (11%) subjects with high-tension glaucoma, 0/9 subjects
      (0%) with normal-tension glaucoma and 3/94 (3.2%) controls. However, association
      of this variant with disease was not significant (P = 0.2 for each phenotype) for
      either high-tension glaucoma or normal-tension glaucoma. A novel variant (P556P
      in exon 16) was found in one subject with open-angle glaucoma and a previously
      described variant (exon 7) was found in a further subject with open-angle
      glaucoma and in one control. No other OPTN variants were identified in this study
      cohort. CONCLUSIONS: Cross-sectional analysis from baseline observations of the
      BMES suggested that the M98K risk-associated allele appeared at a higher
      prevalence in high-tension glaucoma compared with controls, although this finding
      was not statistically significant.

PMID- 15498063
TI  - Quantification of amino acid neurochemistry secondary to NMDA or betaxolol
      application.
AB  - BACKGROUND: Alterations in retinal amino acid neurochemistry are an indicator of
      metabolic function. Glutamate is the primary excitatory amino acid
      neurotransmitter within the retina, and excessive levels of glutamate can
      potentially cause excitotoxicity, in particular, through the N-methyl-D-aspartate
      (NMDA) subtype of glutamate receptor. Anomalies in NMDA receptor function have
      been implicated as causing many neurodegenerative disorders, and overactivation
      leads to neuronal death secondary to metabolic insult. Several pharmaceutical
      agents have been proposed as potential neuroprotective agents against
      excitotoxicity (e.g. betaxolol), yet any effects such drugs have on retinal
      neurochemistry have not been determined. Therefore, the aim of this study was to
      quantify the changes in retinal amino acid neurochemistry secondary to the
      application of NMDA with and without betaxolol. METHODS: Functional NMDA channel
      activation was confirmed in both amacrine and ganglion cells by quantifying the
      entry into these neurones of a channel permeable probe (agmatine: 1-amino-4
      guanidobutane [AGB]). By probing serial thin sections with immunoglobulins
      targeting AGB, glutamate, gamma-aminobutyric acid (GABA) and glycine, it was
      possible to simultaneously study the neurochemical characteristic as well as the
      NMDA-evoked AGB responses of different neurochemical populations of inner retinal
      neurones. RESULTS: The authors have previously shown no accumulation of glutamate
      or GABA within Muller cells following NMDA application. Herein they report
      altered GABA and glycine immunoreactivity, but not glutamate immunoreactivity
      within neurones of the amacrine and ganglion cell layers following NMDA
      application. Finally, the addition of betaxolol did not significantly alter the
      normal neurochemistry of the retina. CONCLUSION: The retina possesses intrinsic
      mechanisms that allow it to maintain metabolic integrity during short periods of
      high NMDA application.

PMID- 15498065
TI  - Pleomorphic adenomas of the lacrimal gland: a clinicopathological analysis.
AB  - PURPOSE: To analyse retrospectively 32 cases of pleomorphic adenoma of the
      lacrimal gland diagnosed over a 10-year period in a tertiary referral eye centre
      from North India. METHODS: The clinical features of 32 cases of pleomorphic
      adenomas diagnosed between 1991 and 2000 were analysed and the histopathological
      features reviewed light microscopically. RESULTS: Among the clinical features, a
      marked male predominance with younger age of presentation and left-sided
      dominance was noted. The duration of symptoms was less than 10 months in 28%
      cases. Histopathologically, the features included presence of cystic degeneration
      (15.6%) and squamous metaplasia (18.7%). Calcification, osteoid formation and
      malignant transformation (3.1% each) were occasionally observed. CONCLUSIONS:
      Pleomorphic adenomas of the lacrimal gland may present with duration of symptoms
      of less than 10 months. Cystic degeneration, squamous metaplasia, calcification
      or ossification may be observed in lacrimal gland pleomorphic adenomas, as has
      been described in pleomorphic adenomas of salivary glands. However, the presence
      of calcification and bone erosion radiologically in a lacrimal gland tumour does
      not necessarily indicate malignancy.

PMID- 15498066
TI  - Syphilis presenting as scleritis in an HIV-positive man undergoing immune
      reconstitution.
AB  - A 45-year-old HIV-positive man receiving highly active antiretroviral therapy
      (HAART) presented with 6 weeks of right-sided headache and right eye pain. He had
      been diagnosed seropositive 2 years previously and screened negative for syphilis
      at that time. Examination demonstrated focal anterior scleritis with underlying
      retinitis and a mild vitritis. He was found to have positive syphilis serology
      and further investigations were consistent with neurosyphilis. Parenteral
      penicillin was commenced with prompt clinical response. This initial presentation
      of syphilis as acute scleritis emphasizes the need for thorough work-up of
      immunocompromised patients with inflammatory ocular disease.

PMID- 15498067
TI  - A tribute to Charles David Kelman MD: ophthalmologist, inventor and pioneer of
      phacoemulsification surgery.
AB  - Charles David Kelman was born in Brooklyn, New York, USA, on 23 May 1930 and
      passed away in Boca Raton, Florida, USA, on 1 June 2004 at the age of 74 years
      after a long battle with cancer. He received a Bachelor of Science degree from
      Tufts University in 1950 and completed medical studies at the University of
      Geneva, Switzerland, in 1956. He was Clinical Professor of Ophthalmology at New
      York Medical College and an Attending Surgeon at New York Eye and Ear Infirmary
      and Manhattan Eye, Ear and Throat Hospital. Although a prolific inventor, he will
      be best remembered for developing phacoemulsification, following his realization
      while sitting in a dentist's chair, that ultrasonic vibrations could be used to
      emulsify the aged crystalline lens through a very small incision. His pioneering
      work revolutionized cataract surgery. He also pioneered cryo-extraction of
      cataracts, the use of freezing for the repair of retinal detachments and designed
      numerous ophthalmic instruments and intraocular lenses. Dr Kelman received
      numerous awards, including the American Academy of Ophthalmology Achievement
      Award (1970), the Ridley Medal from the International Congress of Ophthalmology
      (1990), and the Inventor of the Year Award from The New York Patent, Trademark
      and Copyright Law Association (1992). Most recently (2003), Dr Kelman was
      honoured by the American Academy of Ophthalmology with the Laureate Recognition
      award. Dr Kelman was also an accomplished Broadway producer, composer and jazz
      saxophonist. With his demise, the ophthalmic and medical community lost a famed
      inventor with multifaceted talents and one of the great ophthalmologists of the
      twentieth century.

PMID- 15498068
TI  - Snowflake degeneration of an intraocular lens.
AB  - Snowflake degeneration of intraocular lenses is a recently recognized late
      postoperative complication of cataract surgery. All known cases reported to date
      in the literature have involved polymethyl methacrylate (PMMA) lens optic
      material. Reported herein is an atypical variant of snowflake degeneration of a
      PMMA posterior chamber intraocular lens in an 81-year-old woman, 7 years post
      implantation. The aetiology of the atypical late opacification of the intraocular
      lens is this case is unclear, and no clinical risk factors appear to have been
      identified.

PMID- 15498069
TI  - Nanophthalmic cataract extraction.
AB  - Nanophthalmos is a rare ophthalmic condition with potential sight-threatening
      complications. In addition, nanophthalmic eyes have a high incidence of
      intraoperative and postoperative complications, including uveal effusion and
      retinal detachment. Prophylactic measures to prevent these complications may be
      used. The case is presented where cataract extraction for a nanophthalmic eye was
      performed from a posterior approach in combination with a pars plana vitrectomy
      and gas procedure. To the authors' knowledge, this method of cataract extraction
      has not been reported before for this condition.

PMID- 15498070
TI  - Bilateral subacute angle-closure glaucoma in association with tonic pupils post
      coronary artery bypass graft.
AB  - Anterior and posterior visual pathway disturbances have been reported post
      coronary artery bypass graft surgery. Acute angle-closure glaucoma after general
      anaesthesia has also been well described in the literature. To date, however,
      there are only two cases of angle closure caused by tonic pupils. The case is
      reported herein of bilateral subacute angle-closure glaucoma that occurred
      following coronary artery bypass graft surgery in association with tonic pupils.

PMID- 15498071
TI  - Surgical detachment of Descemet's membrane and endothelium imaged over time by in
      vivo confocal microscopy.
AB  - A 90-year-old woman developed a large circular capsulorhexis-like defect in
      Descemet's membrane as a complication of small incision cataract surgery. Nine
      months post-surgery, in vivo confocal microscopic examination of the temporal mid
      peripheral cornea revealed an endothelial cell density of 934 +/- 69 cells/mm2
      (normal range 1566-3088 cells/mm2). Endothelial pigmented deposits were visible
      as scattered hyper-reflective areas on the posterior endothelial surface.
      Descemet's folds were also noted. In vivo confocal microscopy performed 3 years
      later showed the temporal mid-peripheral corneal endothelial density (in the
      region of the break) was 948 +/- 66 cells/mm2. A reduction of endothelial
      polymegathism and pleomorphism was observed. Imaging in the region of the
      temporal portion of the original Descemet's defect showed well-defined linear
      structures with hyper-reflective edges. Compared to 3 years previously, the
      cornea at the level of Descemet's membrane appeared to have greater reflectivity.
      This case demonstrates how microstructural changes in the cornea can be described
      and analysed over time with the assistance of in vivo confocal microscopy.

PMID- 15498072
TI  - Changing trends in sympathetic ophthalmia.
AB  - Sympathetic ophthalmia is a rare and potentially visually devastating bilateral
      panuveitis, typically following non-surgical penetrating injury to one eye. Three
      patients are presented where sympathetic ophthalmia developed after repeated
      vitreoretinal surgery. Prompt and effective management with systemic
      immunosuppressive agents permitted control of their disease and retention of good
      visual acuity in their remaining eye. Vitreoretinal surgery is an important risk
      factor in sympathetic ophthalmia. Informed consent for vitreoretinal surgery
      (especially in the re-operation setting) should now include the risk of
      sympathetic ophthalmia (approximately 1 in 800). Diverse clinical presentations
      are possible in sympathetic ophthalmia and any bilateral uveitis following
      vitreoretinal surgery should alert the surgeon to the possibility of sympathetic
      ophthalmia. Modern immunosuppressive therapy with systemic steroids and steroid
      sparing agents such as cyclosporin A and azathioprine have improved the
      prognosis. This is particularly so in cases where early diagnosis is made and
      prompt and suitable immunotherapy is commenced.

PMID- 15498073
TI  - Orbital apex syndrome secondary to Pseudallescheria boydii fungal sinusitis in an
      immunocompetent patient.
AB  - Orbital apex syndrome secondary to mucormycosis in immuno-compromised patients is
      well described; however, few reports exist of a paranasal sinus mycetoma
      resulting in this presentation in the immuno-competent patient. The case is
      reported of a 92-year-old man who developed orbital apex syndrome secondary to a
      sphenoidal sinus mycetoma of Pseudallescheria boydii.

PMID- 15498074
TI  - Life-threatening haematological disorders presenting with opthalmic
      manifestations.
AB  - Three cases are reported where life-threatening haematological disorders
      requiring urgent medical intervention presented initially to the ophthalmologist.
      Case one, chronic myeloid leukaemia, presented with bilateral leukaemic
      retinopathy and central retinal vein obstruction due to hyperviscosity. Case two,
      acute myeloid leukaemia, presented with bilateral haemorrhagic retinopathy. Case
      three, aplastic anaemia, presented with bilateral retinopathy due to anaemia and
      thrombocytopaenia resembling bilateral central retinal vein occlusion. In all
      three cases the presence of simultaneous bilateral retinal vascular involvement
      and white-centred haemorrhages suggested an underlying haematological disorder
      and differentiated them from typical retinal venous obstruction. Prompt
      identification of the underlying haematological disorder allows timely referral
      for potentially life-saving treatment.

PMID- 15498075
TI  - Cataracts and driving: experiences of a New Zealand eye clinic population.

PMID- 15498076
TI  - Cataract surgery in an Australian teaching hospital: anterior vitrectomy and
      trainee participation rates.

PMID- 15498077
TI  - Comment on 'Medial canthal tendon repair for moderate to severe tendon laxity'.

PMID- 15498079
TI  - Blue-yellow deficits in diabetes.

PMID- 15498081
TI  - New and experimental approaches to treatment of diabetic foot ulcers: a
      comprehensive review of emerging treatment strategies.
AB  - Diabetic foot ulcers occur in up to 15% of all diabetic patients and are a
      leading cause of nontraumatic amputation worldwide. Neuropathy, abnormal foot
      biomechanics, peripheral vascular disease and external trauma are the major
      contributors to the development of a foot ulcer in the diabetic patient. Therapy
      today includes repeated debridement, offloading, and dressings, for lower grade
      ulcers, and broad spectrum antibiotics and occasionally limited or complete
      amputation for higher grades, requiring a team effort of health care workers from
      various specialties. The large population affected by diabetic foot ulcers and
      the high rates of failure ending with amputation even with the best therapeutic
      regimens, have resulted in the development of new therapies and are the focus of
      this review. These include new off loading techniques, dressings from various
      materials, methods to promote wound closure using artificial skin grafts,
      different growth factors or wound bed modulators and methods of debridement.
      These new techniques are promising but still mostly unproven and traditional
      approaches cannot be replaced. New and generally more expensive therapies should
      be seen as adding to traditional approaches.

PMID- 15498082
TI  - Does autonomic neuropathy play a role in erythropoietin regulation in non
      proteinuric Type 2 diabetic patients?
AB  - AIMS: Erythropoietin (EPO)-deficient anaemia has been described in Type 1
      diabetic patients with both severe autonomic neuropathy (AN) and proteinuria.
      This study was aimed at distinguishing between the effects of AN and nephropathy
      on haemoglobin and EPO levels in Type 2 diabetic patients at an early stage of
      diabetic nephropathy. METHODS: In 64 Type 2 diabetic patients (age 52 +/- 10
      years, duration 10 +/- 9 years) without overt nephropathy and other causes of
      anaemia or EPO deficit, we assessed cardiovascular tests of AN, 24-h blood
      pressure (BP) monitoring, urinary albumin excretion rate (UAE), a full blood
      count, and serum EPO. RESULTS: Although the Type 2 diabetic patients with AN did
      not show differences in haemoglobin and EPO when compared with patients without
      AN, the presence of haemoglobin < 13 g/dl was associated with the presence of AN
      (chi(2)= 3.9, P < 0.05) and of postural hypotension (chi(2)= 7.8, P < 0.05). In a
      multiple regression analysis including as independent variables gender, body mass
      index, duration of diabetes, smoking, creatinine, 24-h UAE, 24-h diastolic BP,
      ferritin, erythrocyte sedimentation rate, and autonomic score, we found that the
      only variables independently related to haematocrit were autonomic score,
      ferritin and erythrocyte sedimentation rate. Finally, the physiological inverse
      relationship between EPO and haemoglobin present in a control group of 42 non
      diabetic non-anaemic subjects was completely lost in Type 2 diabetic patients.
      The slopes of the regression lines between EPO and haemoglobin of the control
      subjects and the Type 2 diabetic patients were significantly different (t = 14.4,
      P < 0.0001). CONCLUSIONS: This study documents an early abnormality of EPO
      regulation in Type 2 diabetes before clinical nephropathy and points to a
      contributory role of AN in EPO dysregulation.

PMID- 15498084
TI  - A prospective study of Type 2 diabetes and depressive symptoms in the elderly:
      the Rancho Bernardo Study.
AB  - AIMS: The association between Type 2 diabetes and depressive symptoms was
      examined prospectively to assess possible causal relationships between the two
      diseases. METHODS: A cohort of 971 men and women aged 50 and older from the adult
      population of Rancho Bernardo, California had an oral glucose tolerance test and
      completed the Beck Depression Inventory (BDI) at two clinic visits, 1984-87 and
      1992-96. RESULTS: Depressive symptoms at baseline were associated with higher
      follow-up levels of non-fasting plasma glucose (P = 0.001) and an increased risk
      of developing Type 2 diabetes [odds ratio (OR) = 2.50; 95% confidence interval
      (CI) = 1.29-4.87], independent of sex, age, exercise and body mass index.
      Conversely, baseline non-fasting plasma glucose was not significantly associated
      with follow-up depressive symptoms and Type 2 diabetes at baseline was not
      significantly associated with the onset of BDI scores > or = 11 by the second
      visit (OR = 0.73; 95% CI = 0.41-1.30). CONCLUSIONS: Depressed mood is more likely
      to be a risk factor for Type 2 diabetes in older adults than the reverse.

PMID- 15498083
TI  - Diurnal blood glucose profiles in women with gestational diabetes with or without
      hypertension.
AB  - AIM: The aim of the study was to establish whether diurnal blood glucose profiles
      differed in women with gestational diabetes (GDM) with different forms of
      hypertensive complications. METHODS: The subjects were patients diagnosed at 26
      32 gestational weeks as having GDM (n = 178). They were classified as being
      normotensive, having chronic hypertension (with or without superimposed pre
      eclampsia on chronic hypertension) or pregnancy-induced hypertension (with or
      without proteinuria). We compared diurnal blood glucose profiles (blood glucose
      taken every 4 h over 24 h) in these three groups. RESULTS: Hypertension
      complicated 43% of the women with GDM. The glucose profiles were similar between
      the three groups, except that in early morning hours (from 04:00 to 08:00 h)
      blood glucose concentrations increased in mothers with chronic hypertension,
      whereas they decreased in the normotensive women. In univariate regression
      analysis, both obesity (BMI > or = 28 kg/m(2)) and chronic hypertension showed
      significant association with blood glucose rise from 04:00 to 08:00 h, but in a
      multiple regression model neither showed significant independent effect.
      CONCLUSIONS: The rise in blood glucose levels during the early morning hours in
      women with GDM and chronic hypertension could reflect greater insulin resistance
      and sympathetic overactivity.

PMID- 15498085
TI  - Long-term renoprotection by perindopril or nifedipine in non-hypertensive
      patients with Type 2 diabetes and microalbuminuria.
AB  - AIMS: To assess the efficacy of an angiotensin converting enzyme (ACE) inhibitor
      (perindopril), a dihydropyridine calcium channel blocker (sustained release
      nifedipine) and placebo in preventing the progression of albuminuria and decline
      in glomerular filtration rate (GFR) in patients with Type 2 diabetes and
      microalbuminaria. METHODS: A prospective, randomized, open, blinded end point
      study of 77 patients allocated to three treatment groups (23 perindopril, 27
      nifedipine, 27 placebo). Drug doses were adjusted to achieve a decrease in
      diastolic blood pressure (DBP) of 5 mmHg in the first 3 months and additional
      therapy was given if hypertension developed (supine DBP > 90 mmHg and/or systolic
      blood pressure (SBP) > 140 mmHg if < or = 40 years; supine DBP > 90 mmHg and/or
      SBP > 160 mmHg if > 40 years). Median follow-up was 66 months, with 37 patients
      being followed for at least 6 years. RESULTS: Blood pressure remained within the
      non-hypertensive range in 83% of perindopril-, 95% of nifedipine- and 30% of
      placebo-treated patients (P < 0.01). In the first 12 months albumin excretion
      rate (AER) decreased by 47% only in the perindopril group (P = 0.04). From 12 to
      72 months, AER gradients increased by 27% per year only in the placebo group (P <
      0.01). After 6 years, macroalbuminuria had developed in 7/15 placebo compared
      with 2/11 in perindopril and 1/11 nifedipine-treated patients (P = 0.05). GFR did
      not change in the first 12 months, but thereafter the median GFR gradient
      (ml/min/1.73 m(2) per year) was -2.4 (P < 0.01) for perindopril-, -1.3 (P = 0.26)
      for nifedipine- and -4.2 (P = 0.01) for placebo-treated patients. The rate of
      decline in GFR for the study group as a whole from 12 months to the end of follow
      up correlated negatively with mean arterial pressure (MAP) (r = -0.38, P < 0.01).
      During a 3-month treatment pause in 29 patients AER tended to increase only in
      the perindopril group (P < 0.07). CONCLUSIONS: Long-term control of blood
      pressure with perindopril or nifedipine stabilizes AER and attenuates GFR decline
      in proportion to MAP in non-hypertensive patients with Type 2 diabetes and
      microalbuminuria.

PMID- 15498086
TI  - Pre-prandial vs. post-prandial capillary glucose measurements as targets for
      repaglinide dose titration in people with diet-treated or metformin-treated Type
      2 diabetes: a randomized controlled clinical trial.
AB  - OBJECTIVE: Repaglinide is an oral anti-diabetic agent that has a short duration
      of action, and is suitable for preventing post-prandial rises in glucose levels.
      Targeting post-prandial glucose levels may lead to lower HbA(1c) levels and rates
      of hypoglycaemia than targeting pre-prandial glucose levels. RESEARCH DESIGN AND
      METHODS: In 42 centres, 193 drug-naive (n = 122) or metformin-treated (n = 71)
      individuals with Type 2 diabetes were randomly allocated to a 40-day period of
      repaglinide dose-titration (starting at 0.5 mg three times daily) based on either
      self-measured pre-prandial or post-prandial glucose levels. They were followed
      for a further 12 weeks and HbA(1c) and hypoglycaemia rates were recorded.
      RESULTS: Repaglinide reduced HbA(1c) by 1.25 and 1.07% in the post-prandial and
      pre-prandial groups, respectively (P for difference = 0.6), and achieved target
      glucose levels in 80.7 and 66.7%, respectively (P = 0.16). The effect of
      titration strategy differed by baseline drug therapy, and was more effective in
      the metformin-treated individuals who experienced a HbA(1c) fall of 0.6 vs. 1.10%
      with pre-prandial vs. post-prandial titration (P for metformin-allocated group
      interaction = 0.043). The rate of hypoglycaemia did not differ by group.
      CONCLUSIONS: In drug-naive individuals with Type 2 diabetes, similar HbA(1c)
      levels are achieved with repaglinide when dosing is adjusted according to either
      post-prandial or pre-prandial levels. Conversely, in metformin-treated
      individuals, repaglinide dosing according to post-prandial levels may lead to
      better glycaemic control than dosing according to pre-prandial levels.

PMID- 15498087
TI  - Amylin replacement with pramlintide as an adjunct to insulin therapy improves
      long-term glycaemic and weight control in Type 1 diabetes mellitus: a 1-year,
      randomized controlled trial.
AB  - AIMS: The autoimmune-mediated destruction of pancreatic beta-cells in Type 1
      diabetes mellitus renders patients deficient in two glucoregulatory peptide
      hormones, insulin and amylin. With insulin replacement alone, most patients do
      not achieve glycaemic goals. We aimed to determine the long-term efficacy and
      safety of adjunctive therapy with pramlintide, a synthetic human amylin analogue,
      in patients with Type 1 diabetes. METHODS: In a double-blind, placebo-controlled,
      parallel-group, multicentre study, 651 patients with Type 1 diabetes (age 41 +/-
      13 years, HbA(1c) 8.9 +/- 1.0%, mean +/- sd) were randomized to mealtime
      injections of placebo or varying doses of pramlintide, in addition to their
      insulin therapy, for 52 weeks. RESULTS: Addition of pramlintide [60 microg three
      times daily (TID) or four times daily (QID)] to insulin led to significant
      reductions in HbA(1c) from baseline to Week 52 of 0.29% (P < 0.011) and 0.34% (P
      < 0.001), respectively, compared with a 0.04% reduction in placebo group. Three
      times the proportion of pramlintide- than placebo-treated patients achieved an
      HbA(1c) of < 7%. The greater reduction in HbA(1c) with pramlintide was achieved
      without an increase in concomitant insulin use and was accompanied by a
      significant reduction in body weight from baseline to Week 52 of 0.4 kg in the 60
      microg TID (P < 0.027) or QID (P < 0.040) pramlintide treatment groups, compared
      with a 0.8-kg gain in body weight in the placebo group. The most common adverse
      event in pramlintide-treated patients was transient, mild-to-moderate nausea.
      CONCLUSIONS: These results show that mealtime amylin replacement with
      pramlintide, as an adjunct to insulin therapy, improves long-term glycaemic and
      weight control in patients with Type 1 diabetes.

PMID- 15498088
TI  - Better long-term glycaemic control with the basal insulin glargine as compared
      with NPH in patients with Type 1 diabetes mellitus given meal-time lispro
      insulin.
AB  - BACKGROUND: Glargine is a long-acting insulin analogue potentially more suitable
      than NPH insulin in intensive treatment of Type 1 diabetes mellitus (T1 DM), but
      no study has proven superiority. The aim of this study was to test superiority of
      glargine on long-term blood glucose (BG) as well as on responses to hypoglycaemia
      vs. NPH. METHODS: One hundred and twenty-one patients with T1 DM on intensive
      therapy on four times/day NPH and lispro insulin at each meal, were randomized to
      either continuation of NPH four times/day (n = 60), or once daily glargine at
      dinner-time (n = 61) for 1 year. Lispro insulin at meal-time was continued in
      both groups. In 11 patients from each group, responses to stepped
      hyperinsulinaemic-hypoglycaemia were measured before and after 1 year's
      treatment. RESULTS: Mean daily BG was lower with glargine [7.6 +/- 0.11 mmol/l
      (137 +/- 2 mg/dl)] vs. NPH [8.1 +/- 0.22 mmol/l (146 +/- 4 mg/dl)] (P < 0.05).
      HbA(1c) at 4 months did not change with NPH, but decreased with glargine (from
      7.1 +/- 0.1 to 6.7 +/- 0.1%), and remained lower than NPH at 12 months (6.6 +/-
      0.1%, P < 0.05 vs. NPH). Frequency of mild hypoglycaemia [self-assisted episodes,
      blood glucose < or = 4.0 mmol/l (72 mg/dl)] was lower with glargine vs. NPH (7.2
      +/- 0.5 and 13.2 +/- 0.6 episodes/patient-month, P < 0.05). After 1 year, NPH
      treatment resulted in no change of responses to hypoglycaemia, whereas with
      glargine plasma glucose, thresholds and maximal responses of plasma adrenaline
      and symptoms to hypoglycaemia improved (P < 0.05). CONCLUSIONS: The simpler
      glargine regimen decreases the percentage of HbA(1c) and frequency of
      hypoglycaemia and improves responses to hypoglycaemia more than NPH. Thus,
      glargine appears more suitable than NPH as basal insulin for intensive treatment
      of T1 DM.

PMID- 15498089
TI  - Sustainability and effectiveness of comprehensive diabetes care to a district
      population.
AB  - AIMS: To evaluate whether diabetes care in a district population can be sustained
      over time and intensive management of multiple risk factors can be achieved
      against a background of rising prevalence of known diabetes and shift of
      responsibility towards primary care. METHODS: Assessment of process and outcome
      measures achieved by a comprehensive diabetes service. Routine data were
      collected from patients registered with diabetes in a district population by
      repeated cross-sectional survey in 1991 (n = 2284 patients) and 2001 (n = 5809
      patients). RESULTS: Between 1991 and 2001 the recording of body mass index (76.8
      vs. 71.3%, P = 0.01) and HbA(1c) measurement (92.2 vs. 86.4%, P < 0.001)
      decreased, whereas recording of smoking status (72.4 vs. 82%, P < 0.001),
      cholesterol level (54.7 vs. 82.5%, P < 0.001) and eye screening result (86.1 vs.
      91.3%, P < 0.001) improved. Surviving patients with Type 2 diabetes had
      significant improvements in systolic blood pressure, diastolic blood pressure and
      cholesterol, significant deterioration in HbA(1c) and creatinine, and no change
      in body mass index. Changes in blood pressure and HbA(1c) over time were similar
      to those reported in the UKPDS. CONCLUSIONS: The delivery of processes and
      outcomes of care to a district population can be sustained at a high level over a
      10-year period within a comprehensive diabetes service. We would suggest that a
      multifaceted complex intervention is required to achieve these results.

PMID- 15498090
TI  - Economic evaluation of therapeutic interventions to prevent Type 2 diabetes in
      Canada.
AB  - AIMS: To compare the health and economic outcomes of using acarbose, an intensive
      lifestyle modification programme, metformin or no intervention to prevent
      progression to diabetes in Canadian individuals with impaired glucose tolerance
      (IGT). METHODS: A model was developed to simulate the course of individuals with
      IGT under each treatment strategy. Patients remain in the IGT state or transition
      from IGT to diabetes, to normal glucose tolerance (NGT) or to death.
      Effectiveness and resource use data were derived from published intervention
      trials. A comprehensive health-care payer perspective incorporating all major
      direct costs, reported in 2000 Canadian dollars, was adopted. RESULTS: Over a
      decade, 70 of the 1000 untreated patients are expected to die and 542 develop
      diabetes. Intensive lifestyle modification is estimated to prevent 117 cases of
      diabetes, while metformin would prevent 52 and acarbose 74 cases. The proportion
      of those who return to NGT also increases with any treatment. While lifestyle
      modification is more effective, it can increase overall costs depending on how it
      is implemented, whereas acarbose and metformin reduce costs by nearly $1000 per
      patient. Lifestyle modification was cost effective, varying from CAD $10 000/LYG
      vs. acarbose. Acarbose costs somewhat more than metformin, but is more effective:
      CAD $1798/LYG. CONCLUSION: The results of this model suggest that the treatment
      of IGT in Canada is a cost-effective way to prevent diabetes and may generate
      savings. While pharmacological treatments tended to be less costly, intensive
      lifestyle modification, if maintained, led to the greatest health benefits at
      reasonable incremental costs.

PMID- 15498091
TI  - Prevalence of the metabolic syndrome among the Inuit in Greenland. A comparison
      between two proposed definitions.
AB  - AIMS: To estimate the prevalence of the metabolic syndrome among Greenland Inuit
      according to the World Health Organization (WHO) definition and the definition
      suggested by the National Cholesterol Education Program (NCEP). METHODS: From
      1999 to 2001, 917 adult Inuit participated in a health survey in Greenland. The
      examination included a 75-g oral glucose tolerance test (OGTT). Body mass index
      (BMI), waist circumference, waist-to-hip ratio and blood pressure were measured.
      Plasma glucose, serum insulin, lipids and urine albumin/creatinine ratio were
      measured. The metabolic syndrome was diagnosed according to the WHO criteria 1999
      and to the working definition suggested by the NCEP 2001. RESULTS: Using the WHO
      and the NCEP criteria, 20.7% and 17.9% of the participants had the metabolic
      syndrome, respectively. There was a moderate agreement between the two
      definitions, kappa = 0.56 (95% CI 0.51-0.61). Of those with the WHO metabolic
      syndrome, 37.9% did not have the NCEP syndrome, and 28.5% of those with the NCEP
      syndrome were not classified with the metabolic syndrome under the WHO criteria.
      Compared with the WHO syndrome, men with the NCEP syndrome had higher mean values
      of waist circumference, BMI and triglycerides, and lower mean values of high
      density lipoprotein (HDL) cholesterol; among women, triglycerides were higher
      with the NCEP syndrome. CONCLUSION: The metabolic syndrome is common among Inuit
      using either the WHO definition or the proposed NCEP definition. The
      classification disagreement is considerable and a universally accepted definition
      is needed.

PMID- 15498092
TI  - Mortality in patients with diabetic neuropathic osteoarthropathy (Charcot foot).
AB  - OBJECTIVE: To determine the mortality of a population of patients diagnosed with
      Charcot neuropathic osteoarthropathy managed by a single specialist unit and to
      compare the results with a control population. METHODS: We have undertaken a
      retrospective analysis of all cases of Charcot foot on the comprehensive database
      which has been maintained at the specialist diabetic foot clinic at the City
      Hospital, Nottingham since 1982. Survival and the incidence of amputation (major
      and minor) was compared with a control population referred with uncomplicated
      neuropathic ulceration. Controls were individually matched for gender, age (+/-2
      years), disease type, disease duration (+/-2 years) and year of referral (+/-3
      years). RESULTS: Forty-seven cases (21 female, 26 male) of Charcot foot were
      identified, of whom 18 (38.3%) had Type 1 diabetes. Mean age and disease duration
      at presentation were 59.2 +/- 13.4 (sd) and 16.2 +/- 11.2 years, compared with
      59.7 +/- 12.6 and 16.3 +/- 11.2 years, respectively, in the controls. Twenty-one
      (44.7%) of those with Charcot had died, after a mean interval of 3.7 +/- 2.8
      years. This compared with 16 (34.0%) after a mean 3.1 +/- 2.7 years in the
      control group. Mean duration of follow-up in the survivors was 4.7 +/- 4.9 years
      (Charcot) and 5.3 +/- 3.9 years (controls). A total of 11 (23.4%) Charcot
      patients had had a major amputation on the side of the index lesion, compared
      with five (10.6%) controls. There was no difference between the two groups (P >
      0.05, Chi-square). CONCLUSIONS: The mortality in this group of patients with
      Charcot foot was higher than expected. Nevertheless, there was no difference
      between those with Charcot and those with uncomplicated neuropathic ulceration.
      It is possible that it is neuropathy, rather than Charcot osteoarthropathy, which
      is independently associated with increased mortality in diabetes. The mechanism
      underlying any such association is not known. There is a need for a formal,
      prospective, multicentre study to investigate the life expectancy and
      cardiovascular risk of those with Charcot osteoarthropathy.

PMID- 15498093
TI  - Isolation of Bordetella trematum from a diabetic leg ulcer.
AB  - BACKGROUND: The species Bordetella trematum (a Gram-negative, opportunistic
      bacterium) was established in 1996. To date, 10 cases of human
      infection/colonization with the pathogen have been described. CASE REPORT: The
      first case of isolation of B. trematum from a diabetic ulcer is reported. Since
      there are no commercially available kits for identification of the organism,
      species diagnosis was based on 16S rDNA sequencing. B. trematum disappeared from
      the ulcer without antimicrobial therapy. CONCLUSION: In the present case, there
      was no evidence for a causative role of the organism in the diabetic foot
      infection, which is in agreement with previously published data. However, B.
      trematum has to be considered when otherwise unclassified Gram-negative rods are
      isolated from infected diabetic ulcers.

PMID- 15498094
TI  - The preventive anti-oxidant action of thiazolidinediones: a new therapeutic
      prospect in diabetes and insulin resistance.
AB  - BACKGROUND: Hyperglycaemia-derived oxygen free radicals may be mediators of
      diabetic complications. METHODS: Recent studies show that hyperglycaemia-induced
      overproduction of superoxide seems to be the first and key event in activation of
      pathways involved in the pathogenesis of diabetic complications. Superoxide
      overproduction is accompanied by increased nitric oxide generation and
      consequently formation of the powerful oxidant peroxynitrite and by poly(ADP
      ribose) polymerase activation. This results in acute endothelial dysfunction and
      activation of inflammation in blood vessels that contribute to the development of
      diabetic complications. RESULTS: Thiazolidinediones are a new class of insulin
      sensitizing agents. They inhibit intracellular free radical overproduction. In
      particular, they inhibit the same pathways involved in hyperglycaemia-derived
      oxidative stress, particularly iNOS and NF-kappaB. Studies in animal models
      suggest that thiazolidinediones can reduce oxidative stress, independent of their
      ability to reduce hyperglycaemia. CONCLUSIONS: The availability of compounds that
      simultaneously decrease hyperglycaemia, restore insulin resistance and inhibit
      pathways activated by high glucose producing oxidative stress signals a promising
      approach.

PMID- 15498095
TI  - Effects of improved glycaemic control maintained for 3 months on cognitive
      function in patients with Type 2 diabetes.
AB  - BACKGROUND AND AIM: In a previous study we failed to find beneficial short-term
      effects of improved glycaemic control on cognitive functioning in patients with
      Type 2 diabetes mellitus. A subgroup of the entire sample was tested again to
      examine the effect of longer-lasting improvement of metabolic control on
      cognitive functioning. METHODS: The cognitive performance of 26 patients with
      Type 2 diabetes was assessed at baseline and 3 months after discharge. Thirteen
      controls were tested at the similar time-points. Attention/concentration,
      psychomotor speed, verbal fluency, verbal memory and depressive symptoms were
      assessed. Improved glycaemic control was generally achieved with insulin therapy
      (20/26). RESULTS: At baseline, there was a trend for diabetic patients to perform
      worse than controls. Both groups improved significantly over 3 months in several
      measures. However, diabetic patients did not improve more than controls.
      CONCLUSIONS: In individuals with long-standing Type 2 diabetes, previous reports
      of improved cognitive capacity following restoration and maintenance of near
      normoglycaemia were not confirmed. This might relate to the type of anti-diabetic
      therapy.

PMID- 15498096
TI  - High risk of diabetes and metabolic syndrome in Indian women with gestational
      diabetes mellitus.

PMID- 15498097
TI  - A case of primary antiphospholipid syndrome and Type 2 diabetes mellitus with
      large artery thromboses successfully treated by abdominal stent implantation.

PMID- 15498098
TI  - Neuronal oxidative damage and dendritic degeneration following activation of CD14
      dependent innate immune response in vivo.
AB  - The cause-and-effect relationship between innate immune activation and
      neurodegeneration has been difficult to prove in complex animal models and
      patients. Here we review findings from a model of direct innate immune activation
      via CD14 stimulation using intracerebroventricular injection of
      lipopolysaccharide. These data show that CD14-dependent innate immune activation
      in cerebrum leads to the closely linked outcomes of neuronal membrane oxidative
      damage and dendritic degeneration. Both forms of neuronal damage could be blocked
      by ibuprofen and alpha-tocopherol, but not naproxen or gamma-tocopherol, at
      pharmacologically relevant concentrations. This model provides a convenient
      method to determine effective agents and their appropriate dose ranges for
      protecting neurons from CD14-activated innate immunity-mediated damage, and can
      guide drug development for diseases, such as Alzheimer disease, that are thought
      to derive in part from CD14-activated innate immune response.

PMID- 15498099
TI  - Peroxynitrite-mediated inactivation of heme oxygenases.
AB  - BACKGROUND: Endogenous nitric oxide (NO) and carbon monoxide (CO) are generated
      by nitric oxide synthase and heme oxygenase, respectively. Like NO, CO has been
      accepted as an important cellular signaling molecule in biological systems. An up
      regulation in both gene and protein expression of heme oxygenase-1 (HO-1) under
      oxidative/nitrosative stress has been well documented, and the protective role of
      HO-1 and HO-2 against oxidative damage is proposed. However, data on the direct
      effect of reactive oxygen/nitrogen species (ROS/RNS) on HO function is
      incomplete. Using gas chromatography to quantify carbon monoxide (CO) formation
      from heme oxidation, we investigated the effects of peroxynitrite (ONOO-) on the
      in vitro catalytic activity of rat spleen (HO-1) and brain (HO-2) microsomal heme
      oxygenases. RESULTS: Exposure to ONOO- led to concentration-dependent but
      reversible decreases in the activity of microsomal rat spleen and brain HO
      activity. Spleen HO activity was 100-fold more sensitive to ONOO--dependent
      inactivation compared to that of the brain, with IC50 values of 0.015 +/- 0.005
      mM and 1.25 +/- 0.25 mM respectively. Inhibition of both rat spleen and brain
      microsomal HO activity was also observed with tetra-nitromethane, a tyrosine
      nitrating agent, as well as two NO donors, S-nitrosoglutathione (GSNO) and
      diethylamine NONOate (DEA-NONOate). However, no additive effect was found
      following the application of NO donors and ONOO- together. CONCLUSION: These
      results indicate that ONOO- may regulate HO-1 and HO-2 activities by mechanisms
      that involve different interactions with these proteins. It is suggested that
      while nitration of tyrosine residues and oxidation of sulfhydryl groups may be
      involved, consideration should be given to other facets of ONOO- chemistry. This
      inhibition of HO activity offers a mechanism for cross talk between the nitric
      oxide synthase and HO systems.

PMID- 15498100
TI  - HLA haplotypes associated with hemochromatosis mutations in the Spanish
      population.
AB  - BACKGROUND: The present study is an analysis of the frequencies of HLA-A and -B
      antigens and HLA haplotypes in two groups of individuals homozygous for the two
      main HFE mutations (C282Y and H63D) and a group heterozygous for the S65C
      mutation. METHODS: The study population includes: 1123 healthy individuals, 100
      homozygous for the C282Y mutation, 138 homozygous for the H63D mutation and 17
      heterozygous for the S65C mutation. HFE and HLA alleles were detected using DNA
      based and microlymphocytotoxicity techniques respectively. RESULTS: An expected
      significant association between C282Y and the HLA-A3/B7 haplotype was found, but
      other HLA haplotypes carrying the -A3 antigen were found: HLA-A3/B62 and HLA
      A3/B44. Also, a significant association between H63D mutation and HLA-A29/B44
      haplotype was found, and again other HLA haplotypes carrying the HLA-A29 antigen
      were also found: HLA-A29/B14 and HLA-A29/B62. In addition, the S65C mutation
      seems to be associated with a HLA haplotype carrying the HLA-A26 antigen.
      CONCLUSION: These findings clearly suggest that HLA-A3/B7 and HLA-A29/B44 are the
      ancestral haplotypes from which the C282Y and H63D mutations originated,
      respectively. The frequencies of these mutations in different populations, their
      geographical distribution, and the degree of the statistical association to the
      ancestral haplotypes, suggest that the H63D mutation must have occurred earlier
      than the C282Y mutation.

PMID- 15498101
TI  - Germinating fission yeast spores delay in G1 in response to UV irradiation.
AB  - BACKGROUND: Checkpoint mechanisms prevent cell cycle transitions until previous
      events have been completed or damaged DNA has been repaired. In fission yeast,
      checkpoint mechanisms are known to regulate entry into mitosis, but so far no
      checkpoint inhibiting S phase entry has been identified. RESULTS: We have studied
      the response of germinating Schizosaccharomyces pombe spores to UV irradiation in
      G1. When germinating spores are irradiated in early G1 phase, entry into S phase
      is delayed. We argue that the observed delay is caused by two separate
      mechanisms. The first takes place before entry into S phase, does not depend on
      the checkpoint proteins Rad3, Cds1 and Chk1 and is independent of Cdc2
      phosphorylation. Furthermore, it is not dependent upon inhibiting the Cdc10
      dependent transcription required for S phase entry, unlike a G1/S checkpoint
      described in budding yeast. We show that expression of Cdt1, a protein essential
      for initiation of DNA replication, is delayed upon UV irradiation. The second
      part of the delay occurs after entry into S phase and depends on Rad3 and Cds1
      and is probably due to the intra-S checkpoint. If the germinating spores are
      irradiated in late G1, they enter S phase without delay and arrest in S phase,
      suggesting that the delay we observe upon UV irradiation in early G1 is not
      caused by nonspecific effects of UV irradiation. CONCLUSIONS: We have studied the
      response of germinating S. pombe spores to UV irradiation in G1 and shown that S
      phase entry is delayed by a mechanism that is different from classical checkpoint
      responses. Our results point to a mechanism delaying expression of proteins
      required for S phase entry.

PMID- 15498102
TI  - The use of warfarin in veterans with atrial fibrillation.
AB  - BACKGROUND: Warfarin therapy is effective for the prevention of stroke in
      patients with atrial fibrillation. However, warfarin therapy is underutilized
      even among ideal anticoagulation candidates. The purpose of this study was to
      examine the use of warfarin in both inpatients and outpatients with atrial
      fibrillation within a Veterans Affairs (VA) hospital system. METHODS: This
      retrospective medical record review included outpatients and inpatients with
      atrial fibrillation. The outpatient cohort included all patients seen in the
      outpatient clinics of the VA Connecticut Healthcare System during June 2000 with
      a diagnosis of atrial fibrillation. The inpatient cohort included all patients
      discharged from the VA Connecticut Healthcare System West Haven Medical Center
      with a diagnosis of atrial fibrillation during October 1999 - March 2000. The
      outcome measure was the rate of warfarin prescription in patients with atrial
      fibrillation. RESULTS: A total of 538 outpatients had a diagnosis of atrial
      fibrillation and 73 of these had a documented contraindication to
      anticoagulation. Among the 465 eligible outpatients, 455 (98%) were prescribed
      warfarin. For the inpatients, a total of 212 individual patients were discharged
      with a diagnosis of atrial fibrillation and 97 were not eligible for warfarin
      therapy. Among the 115 eligible inpatients, 106 (92%) were discharged on
      warfarin. CONCLUSIONS: Ideal anticoagulation candidates with atrial fibrillation
      are being prescribed warfarin at very high rates within one VA system, in both
      the inpatient and outpatient settings; we found warfarin use within our VA was
      much higher than that observed for Medicare beneficiaries in our state.

PMID- 15498103
TI  - Pregnancy weight gain and breast cancer risk.
AB  - BACKGROUND: Elevated pregnancy estrogen levels are associated with increased risk
      of developing breast cancer in mothers. We studied whether pregnancy weight gain
      that has been linked to high circulating estrogen levels, affects a mother's
      breast cancer risk. METHODS: Our cohort consisted of women who were pregnant
      between 1954-1963 in Helsinki, Finland, 2,089 of which were eligible for the
      study. Pregnancy data were collected from patient records of maternity centers.
      123 subsequent breast cancer cases were identified through a record linkage to
      the Finnish Cancer Registry, and the mean age at diagnosis was 56 years (range 35
      - 74). A sample of 979 women (123 cases, 856 controls) from the cohort was linked
      to the Hospital Inpatient Registry to obtain information on the women's stay in
      hospitals. RESULTS: Mothers in the upper tertile of pregnancy weight gain (>15
      kg) had a 1.62-fold (95% CI 1.03-2.53) higher breast cancer risk than mothers who
      gained the recommended amount (the middle tertile, mean: 12.9 kg, range 11-15
      kg), after adjusting for mother's age at menarche, age at first birth, age at
      index pregnancy, parity at the index birth, and body mass index (BMI) before the
      index pregnancy. In a separate nested case-control study (n = 65 cases and 431
      controls), adjustment for BMI at the time of breast cancer diagnosis did not
      modify the findings. CONCLUSIONS: Our study suggests that high pregnancy weight
      gain increases later breast cancer risk, independently from body weight at the
      time of diagnosis.

PMID- 15498104
TI  - Weight loss dynamics during combined fluoxetine and olanzapine treatment.
AB  - BACKGROUND: Fluoxetine and olanzapine combination therapy is rapidly becoming an
      effective strategy for managing symptoms of treatment-resistant depression.
      Determining drug-drug interactions, drug metabolism and pharmacokinetics is of
      particular interest for revealing potential liabilities associated with drug
      augmentation in special patient populations. In the current studies, we
      chronically administered fluoxetine and olanzapine in non-stressed rats to extend
      our previous findings regarding body weight dynamics. RESULTS: Chronic fluoxetine
      (10 mg/kg) and olanzapine (5 mg/kg and 0.5 mg/kg) treatment decreased weight gain
      irrespective of olanzapine dosing. At the 10 mg/kg and 5 mg/kg dose,
      respectively, fluoxetine and olanzapine also significantly reduced food and water
      consumption. This pharmacodynamic event-related effect, however, was not observed
      at the 10 mg/kg and 0.5 mg/kg dosing paradigm suggesting differences in
      tolerability rates as a function of olanzapine dose. The decrease in weight gain
      was not associated with apparent changes in glucose metabolism as vehicle- and
      drug-treated rats showed undistinguishable serum glucose levels. The combination
      of fluoxetine and olanzapine in rats yielded drug plasma concentrations that fell
      within an expected therapeutic range for these drugs in psychiatric patients.
      CONCLUSIONS: These data suggest that fluoxetine and olanzapine treatment
      decreases weight gain in rats; a pharmacodynamic event-related effect that
      differs considerably from what is observed in the clinical condition. The
      possibility of mismatched models regarding body weight changes during drug
      augmentation therapy should be seriously considered.

PMID- 15498105
TI  - Inhibitory effects of proanthocyanidins from Ribes nigrum leaves on carrageenin
      acute inflammatory reactions induced in rats.
AB  - BACKGROUND: The anti-inflammatory effects of proanthocyanidins (PACs), isolated
      from blackcurrant (Ribes nigrum L.) leaves, were analysed using carrageenin
      induced paw oedema and carrageenin-induced pleurisy in rats. RESULTS:
      Pretreatment of the animals with PACs (10, 30, 60 and 100 mg/kg, i.p.) reduced
      paw oedema induced by carrageenin in a dose and time-dependent manner. PACs also
      inhibited dose-dependently carrageenin-induced pleurisy in rats. They reduced (A)
      lung injury, (B) pleural exudate formation, (C) polymorphonuclear cell
      infiltration, (D) pleural exudate levels of TNF-alpha, IL-1beta and CINC-1 but
      did not affect IL-6 and IL-10 levels. They reduced (E) pleural exudate levels of
      nitrite/nitrate (NOx). In indomethacin treated rats, the volume of pleural
      exudate was low, its content in leukocytes and its contents in TNF-alpha, IL
      1beta, IL-6 and IL-10 but not in NOx were reduced. These data suggest that the
      anti-inflammatory properties of PACs are achieved through a different pattern
      from those of indomethacin. CONCLUSION: These results suggest that the main
      mechanism of the anti-inflammatory effect of PACs mainly lies in an interference
      with the migration of the leukocytes. Moreover, PACs inhibited in vivo nitric
      oxide release.

PMID- 15498106
TI  - Symptomatic hypogammaglobulinemia in infancy and childhood - clinical outcome and
      in vitro immune responses.
AB  - BACKGROUND: Symptomatic hypogammaglobulinemia in infancy and childhood (SHIC),
      may be an early manifestation of a primary immunodeficiency or a maturational
      delay in the normal production of immunoglobulins (Ig). We aimed to evaluate the
      natural course of SHIC and correlate in vitro lymphoproliferative and secretory
      responses with recovery of immunoglobulin values and clinical resolution.
      METHODS: Children, older than 1 year of age, referred to our specialist clinic
      because of recurrent infections and serum immunoglobulin (Ig) levels 2 SD below
      the mean for age, were followed for a period of 8 years. Patient with any known
      familial, clinical or laboratory evidence of cellular immunodeficiency or other
      immunodeficiency syndromes were excluded from this cohort. Evaluation at 6- to 12
      months intervals continued up to 1 year after resolution of symptoms. In a
      subgroup of patients, in vitro lymphocyte proliferation and Ig secretion in
      response to mitogens was performed. RESULTS: 32 children, 24 (75%) males, 8 (25%)
      females, mean age 3.4 years fulfilled the inclusion criteria. CLINICAL
      PRESENTATION: ENT infections 69%, respiratory 81%, diarrhea 12.5%. During follow
      up, 17 (53%) normalized serum Ig levels and were diagnosed as transient
      hypogammaglobulinemia of infancy (THGI). THGI patients did not differ clinically
      or demographically from non-transient patients, both having a benign clinical
      outcome. In vitro Ig secretory responses, were lower in hypogammaglobulinemic,
      compared to normal children and did not normalize concomitantly with serum Ig's
      in THGI patients. CONCLUSIONS: The majority of children with SHIC in the first
      decade of life have THGI. Resolution of symptoms as well as normalization of Ig
      values may be delayed, but overall the clinical outcome is good and the clinical
      course benign.

PMID- 15498107
TI  - Differential diagnosis of tuberculous meningitis from partially-treated pyogenic
      meningitis by cell ELISA.
AB  - BACKGROUND: Tuberculous meningitis (TBM) is a major global health problem, and it
      is sometimes difficult to perform a differential diagnosis of this disease from
      other diseases, particularly partially-treated pyogenic meningitis (PTPM). In an
      earlier study, we demonstrated the presence of a 30-kD protein antigen in
      cerebrospinal fluid (CSF) of TBM patients. We have also shown that lymphocytes
      from CSF of TBM patients respond differently to this antigen than do those from
      PTPM patients. The purpose of this study was to develop an assay that can
      discriminate between TBM and PTPM. METHODS: We developed a cell enzyme-linked
      immunosorbant assay (Cell ELISA) to quantitatively measure production of
      antibodies against the 30-kD protein in B cells from CSF of TBM and PTPM
      patients. RESULTS: The cell ELISA yielded 92% (11/12) sensitivity and 92% (11/12)
      specificity for the differential diagnosis of TBM from PTPM. CONCLUSION: When
      induced with the 30-kD protein antigen, B cells derived from CSF of TBM patients
      respond to IgG production within 24 h while those derived from PTPM patients do
      not respond.

PMID- 15498108
TI  - Active collaboration with primary care providers increases specialist referral in
      chronic renal disease.
AB  - BACKGROUND: Late referral to specialist nephrological care is associated with
      increased morbidity, mortality, and cost. Consequently, nephrologists'
      associations recommend early referral. The recommendations' effectiveness remains
      questionable: 22-51% of referrals need renal replacement therapy (RRT) within 3-4
      months. This may be due to these recommendations addressing the specialist,
      rather than the primary care providers (PCP). The potential of specialist
      intervention aiming at slowing progression of chronic renal failure was
      introduced individually to some 250 local PCPs, and referral strategies were
      discussed. To overcome the PCPs' most often expressed fears, every referred
      patient was asked to report back to his PCP immediately after the initial
      specialist examination, and new medications were prescribed directly, and thus
      allotted to the nephrologist's budget. METHODS: In retrospective analysis, the
      stage of renal disease in patients referred within three months before the
      introductory round (group A, n = 18), was compared to referrals two years later
      (group B, n = 50). RESULTS: Relative number of patients remained stable (28%) for
      mild/ moderate chronic kidney disease (MMCKD), while there was a noticeable shift
      from patients referred severe chronic kidney disease (SCKD) (group A: 44%, group
      B: 20%) to patients referred in moderate chronic kidney disease (MCKD) (group A:
      28%, group B: 52%). CONCLUSION: Individually addressing PCPs' ignorance and
      concerns noticeably decreased late referral. This stresses the importance of
      enhancing the PCPs' problem awareness and knowledge of available resources in
      order to ensure timely specialist referral.

PMID- 15498109
TI  - [Progress of studies on molecular immunology of human platelets].
AB  - In autoimmune thrombocytopenic purpura (AITP) specific autoantibodies bind
      platelet GP via their Fab fragments. Both splenic CD5+ B and CD5- B cells produce
      platelet glycoprotein-specific antibodies. There is limited number of antigenic
      determinants, and the GP-specific autoantibodies are derived from a restricted
      number of B-cell clones in chronic AITP. Blocking co-stimulatory signals could
      induce platelet-specific T cell anergy. MMF could be used as a second line agent
      for the treatment of steroid-resistant AITP. Detection of plasma thrombopoietin
      levels play an important role in the differentiation of thrombocytopenic states
      caused by platelet destruction or due to bone marrow hypoplasia. Endogenous TPO
      level is also important on the differential diagnosis of ET and RT. Quinine- or
      heparin-dependent antibodies could induce thrombocytopenia. PCR-SSP is useful for
      the genotyping of the platelet-specific alloantigen HPA. Biotinylated platelets
      have an impaired response to agonists as evidenced by in vitro platelet
      aggregation tests.

PMID- 15498110
TI  - [The mechanism of arsenic trioxide-inducing apoptosis of K562 cells].
AB  - The aim was to investigate the mechanism of arsenic trioxide (ATO) inducing
      apoptosis of K562 cells that express P210Bcr-Abl. Apoptosis was analyzed by cell
      proliferation assay, morphological changes, DNA-PI staining and cell cycle
      analysis. ELISA kits were also used to analyze the concentration of cytosolic
      cytochrome C and activation of caspase-3. Transcriptional levels of Bcl-XL and
      Bcr-Abl were assayed by semiquantitative reverse transcription polymerase chain
      reaction (RT-PCR). The results showed that K562 cells were induced to apoptosis
      after exposure to 2.5 micromol/L ATO for at least 48 hours, and the cell cycle of
      K562 cells was arrested at the G2/M phase. Caspase-3 was activated and there was
      a cytosolic accumulation of cytochrome C. ATO could only reduce the
      transcriptional level of Bcl-XL, but could not down-regulate the Bcr-Abl
      transcriptional level. In conclusion, ATO can induce K562 cells to apoptosis. The
      signal pathway mediated by the cytosolic translocation of mitochondria cytochrome
      C is one of the mechanisms for ATO inducing apoptosis. And the decrease of Bcl-XL
      may induce more apoptosis.

PMID- 15498111
TI  - [Influence of antisense oligonucleotide targeting Chk1/2 on apoptosis of K562
      cell induced by DDP].
AB  - In order to investigate the change of cell-cycle of K562 cells induced by
      cisplatin (DDP) and role of antisense oligonucleotide targeting Chk1/2 on
      apoptosis of K562 cell induced by DDP, the change of cell-cycle was observed by
      means of flow cytometry after different intervals in which the K562 cell were
      treated by DDP. Chk1/2 protein expression was investigated by Western blot and
      confocal microscopy in best condition of transfection of antisense
      oligonucleotide targeting Chk1/2 by lipofection. Apoptosis of K562 induced by DDP
      was investigated by flow cytometry after transfection of antisense
      oligonucleotide targeting Chk1/2. The results showed that K562 cells were
      arrested at S phase at 10 micromol/L of DDP. Transfection with antisense
      oligonucleotide targeting Chk1/2 could inhibit expression of Chk1/2 at different
      levels. The frequency of apoptosis induced by DDP was increased when transfected
      with antisense oligonucleotide targeting Chk1 and/or Chk2. The effect of
      antisense oligonucleotide targeting Chk1 and Chk2 synchronously exceeded that of
      antisense oligonucleotide targeting either Chk1 or Chk2 alone. In conclusion,
      Chk1 and Chk2 may be regarded as targets of therapy for leukemia.

PMID- 15498112
TI  - [Inhibitive effect of previously activated psoralens on K562 cell proliferation].
AB  - The objective was to observe the influence of previously activated psoralens on
      the proliferation of K562 cells, and to provide laboratory data for its clinical
      usage. K562 cells were treated separately with previously and late activated
      psoralens, then their trypan blue exclusion inhibited rates (TBIR), cell
      proliferation inhibited rates (CPIR) and colony forming inhibited rates (CFIR)
      after culture were compared. The results showed that previously activated
      psoralens displayed an inhibiting effect on the proliferation of K562 cells with
      a dose-effect relationship. There was no obvious difference between previously
      and late activated psoralens on TBIR, CPIR and CFIR. In order to exert the
      inhibitive effect of previously activated psoralens, the time of ultraviolet ray
      exposure should be 10 minutes at least, and longer than 12 hours for inhibiting
      K562. The inhibitive effect of previously activated psoratens decreased as the
      time interval from activation to its use was prolonged. The inhibiting effect of
      previously activated psoralens was strongest within 6 hours after activation. In
      conclusion, both previously and late activated psoralens show inhibiting effects
      on the proliferation of K562, which may be able to use an antineoplastic drug in
      clinic.

PMID- 15498113
TI  - [Effect of curcumin on STAT5 signaling pathway in primary CML cells].
AB  - To study the effect of curcumin on signaling pathway of signal transducers and
      activators of transcription (STAT5) in primary newly-diagnosed chronic myelocytic
      leukemia (CML) cells, and to explore the clinical significance of curcumin in the
      treatment of primary CML cells, the cells were randomly divided into 3 groups:
      normal control group, CML cells group, and curcumin group; the cellular
      proliferation was assayed by MTT test; the expression of cellular STAT5 mRNA in
      CML cells was detected by RT-PCR; the activation of STAT5 in CML cell was
      detected by electrophoretic mobility shift assay (EMSA). The results showed that
      the cellular proliferation of curcumin group (OD value 0.640 +/- 0.073) was
      decreased, as compared with that of the CML cells group (OD value 0.856 +/-
      0.083, P <0.01). The expression levels of STAT5 mRNA in CML cells group (integral
      ratio of OD 1.782 +/- 0.156) were significantly greater than that in the normal
      control group (integral ratio of OD 0.289 +/- 0.025, P <0.01). The expression of
      STAT5 mRNA in curcumin group (integral ratio of OD 1.398 +/- 0.126) was
      significantly decreased as compared with that in the CML cells group (P <0.01).
      The activation of STAT5 was significantly increased in CML cells group (gray
      value 5323.375 +/- 515.640) as compared with that in the normal control group
      (gray value 2943.000 +/- 273.377, P <0.01). The activation of STAT5 of curcumin
      group (gray value 4331.750 +/- 398.035) was significantly decreased as compared
      with that of CML cells group (P <0.01). It is concluded that the cellular
      proliferation and the expression of STAT5 mRNA are increased in the primary CML
      cells. The activation of STAT5 in primary CML cells is markedly enhanced. STAT5
      signaling pathway may be involved in the proliferation of primary CML cells.
      Curcumin can inhibit the cellular proliferation and the expression of STAT5 mRNA,
      and down-regulate the activation of STAT5 in primary CML cells. Curcumin may be
      used in treatment of leukemia.

PMID- 15498114
TI  - mitochondrial ceramidase overexpression up-regulates Bcl-2 protein level in K562
      cells, probably through its metabolite sphingosine-1-phosphate.
AB  - Recently, a mitochondrial ceramidase has been identified and cloned, whose
      mitochondrial localization strongly suggests the existence of an unexpected
      mitochondrial pathway of ceramide metabolism that may play a key role in
      mitochondrial functions, especially in the regulation of apoptosis. To explore
      the biological effect of mitochondrial ceramidase on cells, pcDNA 3.1/His-CDase
      plasmid, containing mitochondrial ceramidase cDNA sequence, was transducted into
      K562 cells mediated by liposome, and G418 was used to screen for positive
      colonies. A stable transfected K562 cell line was established and named as
      'K562TC'. The difference between K562 and K562TC cells in chemotheraputic
      cytotoxicity response and serum-withdrawal resistance and Bcl-2 protein
      expression were evaluated by MTT assay, annexin V/PI test, flow cytometry or
      Western blotting, respectively. The results showed that although survival was
      comparable between K562 and K562TC cells after exposed to adriamycin, etoposide
      or arsenious acid, K562TC cells with elevated Bcl-2 protein expression level as
      identified by FCM or Western blotting revealed stronger resistance to apoptosis
      induced by serum withdrawal than their parental cells. Inhibition of
      mitochondrial ceramidase expression in K562TC cells by its specific antisense
      oligodeoxynucleotide was correlated with a decrease in Bcl-2 protein level. N, N
      dimethylsphingosine, a sphingosine kinase inhibitor, depleted intracellular
      sphingosine-1-phosphate production, also abrogated Bcl-2 protein expression in
      K562TC cells, while Bcl-2 protein level in K562 cells was up-regulated by
      exogenous sphingosine-1-phosphate. It is concluded that mitochondrial ceramidase
      overexpression in K562 cells leads to markedly elevated level of Bcl-2 protein
      and results in more resistance to serum withdrawal. This effect is initiated not
      by sphingosine, the direct metabolite of mitochondrial ceramidase, but via
      sphingosine-1-phosphate, its phosphorylated form. This is the first evidence that
      mitochondrial ceramidase, through its sphingoid metabolite sphingosine-1
      phosphate, up-regulates Bcl-2 protein expression in K562 cells.

PMID- 15498115
TI  - [Establishment of K562 cell lines resistant to STI571 and a preliminary
      biological study].
AB  - To produce leukemic STI571-resistant cell lines and to explore the molecular
      mechanism of STI571-resistance, cell lines K562-n and K562-n/VCR were induced by
      exposing cells to gradually increasing STI571 concentration of culture medium to
      have STI571-resistance and major biological characteristics between these
      subclones and the parent cells were compared. The results showed that a STI571
      resistant cell line based on multidrug-resistance was established, which
      exhibited 23.41-fold resistance to STI571, 662.26-fold resistance to VCR and
      cross-resistance to HHT. K562-n/STI was generated from K562-n and had some
      characteristics of MDR. The intracellular accumulation of DNR in K562-n/STI and
      K562-n/VCR/STI were 33.24 and 18.76 respectively. Transcription of mdr-1 gene in
      both K562-n/STI and K562-n/VCR/STI was positive. Cell doubling time of K562-n/STI
      and K562-n/VCR/STI was significantly longer than that in their parent cells (P
      <0.05). And proliferation index was also higher than that in parent cells (P
      <0.05). It is conclusion that the tolerance of K562-n cells to STI571 can be
      augmented by adding low-dose of STI571 into the culture medium repeatedly. K562
      n/STIs expressed MDR at some extent, and transcription of mdr-1 gene in K562
      n/STIs was positive. As K562-n is a cell line used to develop human leukemia in
      nude mice, K562-n/STI and K562-n/VCR/STI 571 will contribute to the study of
      mechanism of STI571-resistance as in vitro and in vivo experimental models.

PMID- 15498116
TI  - [CML cell line K562 cell apoptosis induced by mangiferin].
AB  - This study was aimed to investigate the effects and the mechanism of mangiferin
      on chronic myeloid leukemia cell lines K562 cells in vitro. The antiproliferation
      effects of mangiferin on K562 leukemia cells were tested by tetrazolium salt
      (MTT) method; the apoptosis induced by mangiferin on K562 cell line was explored
      by means of cell morphology, DNA gel electrophoresis and flow cytometry. The
      changes in bcr/abl gene expression was detected by using reverse transcriptase
      (RT)-PCR. The results showed that five different concentrations of mangiferin (25
      - 200 micromol/L) dose-dependently and time-dependently inhibited the
      proliferation of K562 cells, and induced apoptosis in K562 cell line. RT-PCR
      revealed that bcr/abl gene expression was down-regulated when K562 cells had been
      treated with different concentrations of mangiferin. In conclusion, mangiferin
      remarkably inhibits the proliferation of K562 leukemia cells in vitro, and
      induces apoptosis in K562 cell line probably through down-regulation of bcr/abl
      gene expression.

PMID- 15498117
TI  - Preliminary study on the gene expression profiles of bone marrow mononuclear
      cells from patients with myelo-dysplastic syndrome by using cDNA microarray.
AB  - cDNA microarray, recently applied to analyze gene expression profile of cancers,
      was difficult to be utilized in myelodysplastic syndrome (MDS) for a special need
      of excessive mRNA hardly provided by ordinary bone marrow aspiration in MDS
      patients. The aim of this study was to investigate the feasibility of exploring
      the molecular events underlying MDS by using cDNA microarray and mixing mRNA from
      multiple patients. A commercially purchased BioStar H141 cDNA microarray
      containing 14,110 clones of cDNA or EST was employed to analyze the gene
      expression profile of bone marrow mononuclear cells from two cases of MDS. Equal
      amount of total RNA from each patient was mixed, reversely transcribed to cDNA
      and labeled with Cy5. Mixture of Cy5-labeled cDNA and Cy3-labeled cDNA from
      normal bone marrow cells was concomitantly hybridized to H141 microarray in
      duplicate. In H141 chips, 1,064 cDNAs were spotted at least twice targeting
      different fragments of a single gene cDNA. The results showed that among these
      1,064 cDNA clones, the expression level of 625 (58.7%) and 630 (59.2%) ones was
      consistent within these two chips, respectively, 297 (27.9%) and 191 (18.0%)
      inconsistent, 21 (2.0%) and 11 (1.0%) in opposite. Among 411 duplicately spotted
      cDNAs with complete data, expression levels of 400 (97.3%) was consistent between
      two chips. 488 genes with known function were identified as differentially
      expressed in MDS, among which 101 genes were involved in hematopoiesis
      regulation, including those encoding transcription factors, cell cycle-regulating
      proteins, metabolism-relating enzymes, and adhesive molecules. It is concluded
      that cDNA microarray can be used for profiling gene expression of mixed MDS
      samples and replication shall be necessary for reducing the data bias caused by
      experimental operation.

PMID- 15498118
TI  - [Effect of sodium butyrate in combination with ATRA on the
      proliferation/differentiation of MDS cell line SKM-1].
AB  - The study was purposed to explore the molecular mechanisms of sodium butyrate
      (NaB) action on SKM-1 cell proliferation/differentiation and to study its
      synergistic effect with all-trans retinoic acid (ATRA). SKM-1 cells were grown in
      the absence or presence of NaB and/or ATRA; the percentage of viable cells was
      determined by trypan blue exclusion; differentiation was investigated by nitro
      blue tetrazolium (NBT) reduction; adhesion molecules of cell surface were
      analysed by FACS; cell cycle distribution was studied after DNA staining by
      propidium iodide; D-type cyclins, CDK and P21 mRNA were detected by reverse
      transcription-polymerase chain reaction (RT-PCR). The results showed that NaB
      and/or ATRA blocked cells mainly in the G0/G1 phase of the cell cycle; ATRA
      inhibited the mRNA expression of CDK6, CDK4, cyclin D3 and cyclin D1; NaB
      inhibited the mRNA expression of CDK2, cyclin D2 and cyclin D1; ATRA and NaB
      inhibited the mRNA expression of CDK6, CDK4, CDK2, cyclin D1, cyclin D2 and
      cyclin D3; ATRA and/or NaB both stimulated p21 expression at the mRNA levels. It
      is concluded that the NaB effect on cell proliferation/differentiation may be
      linked to its ability to induce expression of p21 mRNA and inhibit the cyclin D
      CDK complexes. These observations support the claim that NaB has the synergistic
      effect with ATRA.

PMID- 15498119
TI  - [Study on the relationship between the inhibitors of apoptosis proteins and the
      apoptosis of myelodysplastic syndrome cell line cells induced by aclacinomycin in
      vitro].
AB  - To explore the correlation between the cellular inhibitors of apoptosis proteins
      (cIAPs) and the apoptosis of myelodysplastic syndrome (MDS) cell line (RAEB type)
      cells induced by aclacinomycin (ACM), the apoptosis of MDS cell line MUTZ-1 cells
      induced by ACM was analyzed with terminal deoxyribonucleotidy transferase
      mediated dUTP-biotin nick end labeling (TUNEL) technique. By using semi
      quantitative reverse transcriptase polymerase chain reaction (RT-PCR), the
      expression levels of cIAP-1 and cIAP-2 mRNA in MUTZ-1 cells were assayed. The
      results showed as follow: (1) Using 0.5 micromol/L, 1.0 micromol/L ACM treated
      cells for 24 hours, the relative expression level of cIAP-1 mRNA (cIAP-1/GAPDH)
      was lower than those in the untreated cell group (P=0.002, 0.0002, respectively).
      (2) Using 0.5 micromol/L ACM treated for 6, 12, 24 hours, the relative expression
      level of cIAP-1 mRNA was 0.95 +/- 0.04, 0.73 +/- 0.05, 0.38 +/- 0.07,
      respectively and the relative expression level of cIAP-1 mRNA was correlated
      negatively with the time treated by ACM (r=-0.996, P <0.01). (3) Using 0.5
      micromol/L ACM treated for 3, 6, 12, 24 hours, the relative expression level of
      cIAP-2 mRNA was 1.17 +/- 0.06, 0.91 +/- 0.03, 0.69 +/- 0.07 and 0.00 +/- 0.00,
      respectively and relative expression level of CIAP-2 mRNA was correlated
      negatively with the time treated by ACM (r=-0.091, P <0.01). (4) The percentages
      of TUNEL positive cells were correlated negatively with the relative expression
      level of CIAP1 and CIAP2 mRNA (r=-0.984, -0.959 and P=0.002, 0.013 respectively)
      when treated with increasing concentration of ACM. In conclusion, ACM can induce
      significantly MUTZ-1 cell apoptosis via suppressing expression of anti-apoptotic
      gene cIAP-1 and cIAP-2 mRNA.

PMID- 15498120
TI  - [Study on negative regulatory factors in bone marrow mononuclear cells of
      myelodysplastic syndromes].
AB  - To explore the difference of negative regulatory factors among T lymphocyte
      subsets in bone marrow (BM) of myelodysplastic syndromes (MDS) and their
      relations to apoptotic gene Fas, different lymphocyte subsets in BM were
      categorized by monoclonal antibodies with 3 color fluorescence using flow
      cytometry, and the intracellular cytokines such as tumor necrosis factor-alpha
      (TNF-alpha), interferon-gamma (IFN-gamma) were determined following marrow cells
      culture. Then Fas mRNA of bone marrow mononuclear cells (BMMNC) were examined by
      RT-PCR. The results showed that TNF-alpha, IFN-gamma levels in BM of MDS both
      increased, the former produced by cells CD4+CD45RO+, CD8+CD45RO+, the latter by
      cells CD4+CD45RO+, CD8+CD45RO+, CD8+CD45RA+, in which the cells CD8+CD45RO+ were
      dominant. Fas mRNA expression had relationship with IFN-gamma produced by T cells
      but not with TNF-alpha. It is concluded that in hematopoietic microenvironment of
      MDS, not only the T lymphocyte subsets are in disorder, but also negative
      regulatory factors secreted by T lymphocyte increase. T lymphocytes play an
      important role in producing IFN-gamma in patients with MDS.

PMID- 15498121
TI  - [Differentiation and increase of dendritic cells from umbilical cord blood in
      vitro].
AB  - The aims of this study were to analyze the composition of umbilical cord blood
      cells (UCBC), to examine the characteristics of dendritic cells (DC) before and
      after culture, to search the method of differentiation and increase of DC in
      vitro and to appraise surface antigen from UCBC. Twelve units of umbilical cord
      blood were collected from May 2002 to September 2002. Peripheral blood
      mononuclear cells of 9 cases were collected from healthy adult donors. The nature
      of UCBC was freshly determined and then UCBC were cultured for 1, 2, 3 and 4
      weeks with granulocyte-monocyte colony-stimulating factor (GM-CSF), interleukin 3
      (IL-3), recombinant human stem cell factor (SCF) and EPO. Method of flow
      cytometry was used to determine the number of DC and cell surface antigens before
      and after culture by using monoclonal antibodies. The monoclonal antibodies
      included CD4, CD8, CD19, CD34, CD38, CD83, CD1a, CD11c and CDw123. The results
      showed that amounts of CD34+ progenitors in peripheral blood cells were 0.02 x
      10(5)/ml, and amounts of CD34+ progenitors in human UCBC were 0.22 x 10(5)/ml.
      UCBC cultured for 1, 2, 3 and 4 weeks with GM-CSF, IL-3, EPO and SCF were shown
      to differentiate into CD1a+ CD11c+ CD83+ CDw123+ DC. Numbers of DC from UCBC
      remarkably generated in 2-4 weeks and then decreased in number. By culture with
      cytokines DC increased up to (10.6 - 28.2) x 10(5)/ml in actual numbers. It is
      concluded that the mononuclear cells of UCB are able to differentiate into CD1a+,
      CD83+, CD11c+ and CDw123+ DC when UCBC are cultured with proper cytokines of GM
      CSF, SCF, EPO and IL-3 for 2-4 weeks. These DCs as antigen presenting cells are
      possibly effective in cancer immunotherapy.

PMID- 15498122
TI  - [Differentiation and function of human dendritic cells influenced by heat shock
      protein gp96 purified from K562 cells].
AB  - This study was to establish the method of purifying heat shock protein GP96 from
      K562 cells and explore the differentiation and function of human DC influenced by
      heat shock prolein (HSP). Using ammonium sulfate precipitation, conA-sepharose
      affinity chromatography and DEAE-sephacel anion exchange chromatography GP96 from
      K562 cells lysate was isolated and purified. The identification of the purified
      protein was controlled by Western blot with anti-human GP96 IgG. Human dendritic
      cell derived from peripheral blood mononuclear cell were cultured with purified
      GP96. The phenotype changes of DC were analyzed by flow cytometry and MLR was
      detected by MTT. The results showed that 60-80 microg GP96 was purified
      successfully from 1 x 10(10) K562 cells. DC stimulated with HSP-GP96 had higher
      expression rates of CD83, CD86, HLA-DR and lower expression rates of CD1a and had
      stronger ability to induce T cells proliferation. It is concluded that heat shock
      protein GP96 can be isolated and purified from K562 cells and could induce
      maturation of dendritic cell. HSP-DC vaccine show stronger ability to induce T
      cell proliferation than DC.

PMID- 15498123
TI  - The induction and function study on dendritic cells derived from blasts from
      patients with acute myelogenous leukemia.
AB  - To investigate the induction method and function of dendritic cells (DC) derived
      from acute myelogenous leukemia (AML) blasts in vitro, cytokine-supplemented
      suspension cultures of leukemia blasts in 25 AML patients were performed.
      Mononuclear cells were cultured for 8 to 12 days using recombinant human
      granulocyte-macrophage colony stimulating factor (rhGM-CSF), recombinant human
      interleukin-4 (rhIL-4) and recombinant human tumor necrosis factor-alpha (rhTNF
      alpha). Morphology, phenotype, cytogenetics, and function of induced cells were
      studied. The results showed that after culture for 3 days, cells in 20/25 AML
      cases demonstrated an increase in size with dendritic morphology. After culture
      for 8 - 9 days, the percentage of such cells reached peak. When cultured for 12
      days, the total number of cells and the number of cells with DC morphology
      decreased greatly. Phenotypic analyses of cells (11/20 cases) were measured by
      flow cytometry before and after culture. Before culture, cells did not express
      CD1a, CD80 and CD83, while expressed CD54, CD86 and HLA-DR with low frequency.
      After culture, cells upregulated CD1a, CD80, CD83, CD54, CD86 and HLA-DR
      significantly. A marked increase of the T-cell stimulatory capacity could be
      generated in Allo-MLRs. FISH confirmed the leukemic origin of generated cells. In
      conclusion, leukemia-derived DC can be generated from AML blasts using cytokine
      combination (GM-CSF, IL-4, and TNF-alpha) in vitro.

PMID- 15498124
TI  - [Expression of VEGFA, VEGFC, angiopoietin-1, angiopoietin-2 and their receptors
      on development liver during gestation of weeks 3-12 of human embryo].
AB  - The aim was to study the expression of VEGF-A, VEGF-C, angiopoietin-1,
      angiopoietin-2 and their receptors on development liver during gestation of weeks
      3-12 of human embryo. Human embryo contingently aborted at 3-12 weeks of
      gestation were collected with signed agreements of the pregnant women suffered
      from accidental abortions. The specimens were fixed by 4% paraformaldehyde and
      embedded by paraffin. 5 microm serial sections were made. HE staining,
      immunohistochemistry method and light-microscope were employed. The results
      showed that at 4-5 weeks of development, liver was constituted by a few hepatic
      cords. Hematopoietic cell or blood cells were undetectable in the 4 week of
      gestation. A few cells which were larger, rounded and nucleared cells appeared
      and expressed VEGFA, flt-4 and Tie-2 proteins strongly in liver at 5 weeks of
      gestation. The number of these immuno-positive cells was highest in the 7th week
      and decreased at 11-12 weeks of gestation. These cells expressed flk-1
      transiently in the 6th week. VEGF-C and flt-1 were expressed by hepatic cells
      from weeks 7 to 12 of gestation. The immuno-positive products were deposited in
      plasma of hepatic cells. Angiopoietin-1, angiopoietin-2 and Tie-2 were detectable
      on those cells which expressed VEGFA, flt-4 and Tie-2 from weeks 5 to 12 of
      gestation. The expression of angiopoietin-1 and angiopoietin-2 were weakly and
      Tie-2 was strongly. They were expressed weakly too by hepatic cells at 5 to 12
      weeks of gestation. All factors and their receptors were undetectable on vascular
      endothelial cells at 4-12 weeks of gestation. It is concluded that the expression
      patterns of VEGF family on cells of liver are different before and after 7 weeks
      of gestation. The hematopoiesis in fetal liver may be related to development of
      hepatic cell.

PMID- 15498125
TI  - [Study on the expression of hematopoietic growth factor gene in human umbilical
      vein endothelial cells using gene chip].
AB  - In order to detect the hematopoietic growth factor gene expressed in human
      umbilical vein endothelial cells using gene chip, human umbilical vein
      endothelial cells (ECV304) were cultured in vitro and divided into VEGF group and
      control group in same medium. 50 ng/ml hVEGF165 was added in the VEGF group.
      After culture for 24 hours all cells were collected for total RNA extraction.
      Then, cDNAs were marked with Cy3 and Cy5 for control group and VEGF group,
      respectively, and hybridized with gene chip. Hybridization signals were collected
      and analyzed following scanning by laser co-focal microscopy. The results showed
      that a large number of hematopoietic growth factor and receptor genes (Epo/R, GM
      CSF/R, G-CSF/R, LIF, IL-3, TPO, Flt-3, SCF) were expressed in both groups, while
      many other growth factors (VEGF, IGF2, PDGFA, PDGFB, TGFbeta1) and receptors
      (neuropilin-1, neuropilin-2, TGFbeta-R1)were expressed. The differentially
      expressed genes amounted to 24. It is concluded that many hematopoietic growth
      factors and receptors expressed by hUVECs could be analyzed in a short period by
      using gene chip, which provides a powerful method for further studies on
      characteristics of vascular endothelial cells.

PMID- 15498126
TI  - [Effect and mechanism of VEGF antisense phosphorothioate deoxynucleotides on HL
      60 leukemic cells].
AB  - To explore dose-effect or time-effect of vascular endothelial growth factor
      (VEGF) antisense phosphorothioate oligodeoxynucleotides (AS PS-ODN) on growth of
      HL-60 cells, and to study the effect mechanism so as to find new role of VEGF,
      A7, which was the most effective one of AS PS-ODN selected with computer-aided
      design and experimental assay, contains 20-DNA modified with phosphorothioate and
      was tranferred into cells mediated with lipofectin. After culture for 72 hours,
      inhibitive rate of cell growth was detected with MTT methods, viable cells were
      counted with trypan blue exclusion each 24 hour, cell configuration and apoptosis
      were observed with Geimsa staining and flow cytometry respectively, level of VEGF
      protein was detected with VEGF ELISA kit. The results showed that A7 is able to
      inhibit cell growth of HL-60 in dose-depending manner of AS PS-ODN, to down
      regulate VEGF protein expression significantly, and not to induce apoptosis of HL
      60 cells. It is concluded that there is possibility that the inhibition effect of
      VEGF AS PS-ODN on HL-60 cell growth is to restrain cell proliferation without
      inducing apoptosis of HL-60 cell, which would interpret that endogenous VEGF
      proteins have a capacity of promoting proliferation of HL-60 cell.

PMID- 15498128
TI  - [Application of sequential and quantitative analysis of donor chimerism in donor
      lymphocyte infusion].
AB  - In order to study the value of sequential and quantitative analysis of chimerism
      in determination of optional time of donor lymphocyte infusion (DLI) and
      prediction of efficacy of DLI, six patients with leukemias who relapsed or failed
      of engraftment were treated with DLI. Serial and quantitative analyses of donor
      chimerism (DC) both prior to and following DLI were performed by multiplex PCR
      amplification of STR markers (STR-PCR) and capillary electrophoresis with
      fluorescence detection. The results showed that at the time of relapse or graft
      rejection, STR-PCR indicated the decreasing donor chimerism in all six patients,
      at levels ranging from 27.3% to 85.7%. The declining value of DC (<90%) was
      detected in four patients at 26 days before relapse or graft rejection diagnosed
      clinically. Therefore the decrease of value of DC can be identified the high risk
      of relapse or graft failure and can be used to guide DLI implementation at early
      stage. In this study the clinical response were seen in two patients, the value
      of DC in these patients increased with convertion to a predominant donor profile
      (>90%) or converted to stable FDC shortly after DLI, while in the patients
      without clinical response, the level of DC decreased persistently or declined
      after transient increase. Three patients without response received second DLI. It
      is concluded that the monitoring of chimerism is proved to be a valuable to
      determine the optional time point of DLI and to early evaluate the efficacy of
      DLI. Furthermore, it can present a rational basis for treatment of
      intensification in the patients who did not respond to first-line DLI treatment.

PMID- 15498127
TI  - [Effect of transforming growth factor-beta1 on proliferation and apoptosis of
      mononuclear cells of cord blood].
AB  - To explore the mechanism of transforming growth factor-beta1 (TGF-beta1) effect
      on umbilical cord blood mononuclear cells proliferation and apoptosis, 5-bromo-2'
      deoxyurine (BrdU) incorporation assay was adopted to detect effect of TGF-beta1
      on synthesis of DNA in cells. Western blot method was used to examine effect of
      TGF-beta1 on expression of cyclin A, Cyclin D1, CDK2 and CDK4 in G1 phase of cell
      cycle. Giemsa staining and flow cytometry (FCM) were performed to detected effect
      of TGF-beta1 on cell apoptosis. The results showed that (1) after culture of
      cells with IMDM containing 10% FBS, 10% FBS + 1 ng/ml TGF-beta1, 10% FBS + 2
      ng/ml TGF-beta1 or 10% FBS + 5 ng/ml TGF-beta1 for 12 hours the OD values of TGF
      beta1 group were significantly lower than control group (P <0.01); after culture
      for 24 hours the OD values of 1 ng/ml TGF-beta1 group had no significant
      difference compared with control group (P >0.05), but the OD values of 2 ng/ml
      and 5 ng/ml TGF-beta1 groups were significantly lower than control group (P
      <0.05). (2) 2 ng/ml TGF-beta1 could significantly inhibit the production of
      cyclin A, cyclin D1, CDK2 and CDK4, the protein levels were significantly lower
      than control group. (3) when the cells were co-cultured with 2 ng/ml TGF-beta1
      for 12 and 24 hours, Giemsa staining and FCM detection could display typical
      apoptosis, the apoptosis rates were 14.42% and 31.98%, while apoptosis rate in
      control were 4.71% and 5.76%. It is concluded that TGF-beta1 can inhibit
      production of G1 cyclins and CDKs of umbilical cord blood mononuclear cells,
      arrest cells in the G1 phase of cell cycle and induce cell apoptosis. Thus, TGF
      beta1 may be an important negative modulator in hematopoiesis.

PMID- 15498129
TI  - [Establishment of nonmyeloablative allogeneic stem cell transplantation model in
      H-2 haploidentical mice and its related study].
AB  - To explore the feasibility of nonmyeloablative conditioning regimens,
      hematopoietic reconstitution, chimera level and the occurrence of GVHD after
      nonmyeloablative allogeneic stem cell transplantation in H-2 haploidentical mice,
      CB6F1 mice were used as the recipient and were divided into 3 groups, mice were
      pretreated five days before transplantation. Group A was pretreated with
      myeloablative conditioning regimens (TBI with 10.5 Gy), group B was pretreated by
      TBI (2 Gy) + Ara-C + Cy and group C-TBI (2 Gy) + Ara-C + CY + Flu, respectively.
      For all recipient mice, the prevention of GVHD was not given, and 2 x 10(7) bone
      marrow cells mixed 1 x 10(7) spleen cells from C57BL/6 mice were injected through
      tail vein on day 0, and then hematopoietic recovery, engraftment and GVHD of
      recipients were observed. The results of chimera detection after transplantation
      showed that the engraftment of group A remained full donor chimerism, and
      engraftments of group B and group C were associated with mixed chimerism or full
      donor chimerism, but the chimerism of group B remained below 80% and tended to
      decrease after 50 days whereas chimerism of group C was above 80% (chimerism
      close to or being full donor type) and preserved even after 50 days. GVHD
      occurred in all the recipient mice due to that prevention was not given, wherein
      the occurrence and death rate of GVHD in group A was obviously higher than that
      of group B and group C (P <0.01), but there was no statistical difference between
      group B and group C. In conclusion, the nonmyeloablative conditioning regimens
      mainly based on fludarabine can form stable and lasting engraftment in the body
      of recipients. The mixed chimerism established in recipients induce tolerance of
      transplantation and decrease or avoid the occurrence of GVHD.

PMID- 15498130
TI  - [Dynamic examination of the serum erythropoietin levels following ABO
      incompatible allogeneic hematopoietic stem cell transplantation and its
      implications].
AB  - To evaluate the dynamic changes of erythropoietin (EPO) and its significance
      following ABO-incompatible allogeneic hematopoietic stem cell transplantation
      (allo-HSCT), sequential changes in serum EPO levels were measured by enzyme
      linked immunosorbent assay (ELISA) in 11 patients receiving allo-HSCT from ABO
      incompatible donors. The results showed that the mean EPO level was markedly
      elevated and reached to its highest level at 0 day-2 week after allo-HSCT (233.73
      +/- 81.95 mU/ml and 226.07 +/- 113.87 mU/ml respectively, P >0.05). Although the
      EPO levels were significantly lower at 1 month (128.49 +/- 108.92 mU/ml, P <0.05)
      and after the reversion of blood type (73.07 +/- 68.85 mU/ml, P <0.05), they were
      still elevated up to 2 months after allo-HSCT. The EPO levels always had
      significant positive correlation with the RBC transfusions. At 0 day and 4 week
      after allo-HSCT, the EPO levels had significant negative correlation with the Hb
      levels; at 6 and 8 week after allo-HSCT, the EPO levels had no relation with the
      Hb levels, they had significant positive correlation with the time of erythrocyte
      recovery and anti-A isoagglutinin titers at the same time. It is concluded that
      serum erythropoietin levels continuously increasing following ABO-incompatible
      allogeneic allo-HSCT suggest that exogenous recombinant human erythropoietin
      treatment for anemia may not be beneficial.

PMID- 15498131
TI  - [Inhibition effect of bone marrow mesenchymal stem cells on T-lymphocyte
      proliferation through up-regulation of CD8+CD28- T cells].
AB  - The aim of this study was to explore effect of CD8+CD28- T-lymphocyte in the
      inhibition of mesenchymal stem cells (MSC) on T-lymphocyte proliferation. T cells
      were harvested by using nylon column and CD8+ T cells were sorted by magnetic
      beads; the T-lymphocyte proliferation in the presence of PHA was evaluated by
      MTT; the proportion of CD8+CD28- T cells was assayed by fluorescence-activated
      cell sorter (FACS). The results showed that MSC inhibited T-lymphocyte
      proliferation and the inhibitory effect depended on the amount of MSC; the data
      of FACS indicated that in the CD8+ T cells co-cultured with MSC, CD8+CD28- T
      cells were up-regulated significantly, compared with the non-treated CD8+ T
      cells. In conclusion, MSC perform their immunosuppressive function by up
      regulation of CD8+CD28- T cells.

PMID- 15498132
TI  - [Study on non-programmed process using dimethyl sulfoxide and hydroxyethyl starch
      as cryoprotectants in cryopreservation of cord blood hematopoietic cells].
AB  - This study was aimed to search for effective cryoprotectants and freezing methods
      used in cord blood bank (CBB) for cryopreservation of cord blood hematopoietic
      stem cells. The non-programmed group using 8% final concentration of dimethyl
      sulfoxide (DMSO) and 5% final concentration hydroxyethyl starch (HES) (molecular
      weight 120,000) as protectants and group of conventional of programmed controller
      method using 10% DMSO only as cryoprotectant in cryopreservation of cord blood
      hematopoietic stem cells were compared. In each of the two groups, 15 cord blood
      units were used. In non-programmed group, cord blood units put in -80 degrees C
      refrigerator for 24 hours as a transitional step before deep-freezing in liquid
      nitrogen, when both of DMSO and HES had been added. The recoveries of the nuclear
      cells number, the yield of granulocyto-macrophage colony forming units (CFU-GM)
      and the cells viability in cord blood units before preservation and after thawing
      were tested for both methods. The results showed that no significant difference
      was found in above assays between two groups. The clinical application results
      also showed that hematopoietic engraftment rates after infusion were similar in
      both groups. It is concluded that the non-programmed method by -80 degrees C
      refrigerator as a transitional step and using the combined two protectants seems
      simple in operation and effective in clinical transplantation as well as the
      conventional programmed method.

PMID- 15498133
TI  - [Gene polymorphisms of rennin-angiotensin system and coronary artery thrombosis
      disease].
AB  - To investigate the distribution frequencies of angiotensin-converting enzyme
      (ACE), angiotensinogen (AGT), angiotensin II I type receptor (AT1R) genotypes in
      Chinese, to find the relationships between polymorphisms of ACE, AGT and AT1R
      gene, and coronary artery thrombosis disease (CATD) and to study the interactions
      of themselves, PCR and PCR-RFLP techniques were performed to determine the
      genotypes of ACE, AGT and AT1R gene in CATD group (192 cases) and control group
      (110 cases). The results showed that (1) genotype frequencies of the three
      polymorphisms in the control group were 12.2% (DD), 43.9% (ID), and 43.9% (II)
      for the ACE I/D polymorphism; 8.2% (MM), 36.7% (MT), and 55.1% (TT) for AGT M235T
      polymorphism; 91.8% (AA), 8.2% (AC) for AT1R A1166C polymorphism respectively;
      (2) there were no significant differences between patients in either the control
      group, the non-MI group, or the MI group in any genotype frequency of all these
      three genes (P >0.05). (3) the odds ratio for CATD in subjects carrying both AT1R
      AC and AGT-TT genotype was 3.517 (95% CI 0.988 - 12.527), compared with those
      carrying AT1R-AA and AGT-TT genotype and was 15.000 (95% CI 1.940-115.963),
      compared with those carrying AT1R-AC and AGT-MM/MT genotype. In subjects with
      AT1R-AC genotype, there was also a great difference of ACE D allele frequency
      between control group and CATD group (P=0.017). It is concluded that genotype
      frequencies of ACE I/D polymorphism, AGT M235T polymorphism, and AT1R A1166C
      polymorphism were obviously different from those in western countries. Although
      these three polymorphisms were not independent risk factors for CATD or
      myocardial infarction (MI) in Chinese, AT1R-AC genotype has a significant
      synergistic effect with AGT-TT genotype. There is also a obvious interaction
      between AT1R-AC genotype and ACE D allele.

PMID- 15498134
TI  - [Comparison of platelet activators used in slide platelet aggregation test].
AB  - The study was purposed to explore the suitable platelet activators to be used in
      slide platelet aggregation test. Experiments were as follows: (1) to detect the
      intensity and time in 15 healthy donors' platelet aggregation tests induced by
      cationic propyl gallate (c-PG) and the usual platelet activators: ADP, collagen,
      epinephrine, arachidonic acid and ristocentin, respectively; (2) to detect the
      time in platelet aggregation tests of 15 healthy donors induced by c-PG and the
      above usual platelet activators respectively after addition of PGI2, cAMP or
      EDTA; (3) to detect the time in 15 healthy donors' platelet aggregation tests
      induced by c-PG after addition of heparin; (4) to detect the intensity and time
      of platelet aggregation induced by c-PG at the platelet count of (240-15) x
      10(9)/L, (5) to detect the time of platelet aggregation induced by c-PG in eight
      patients each of whom had taken 100 mg aspirin per day for five days. The results
      showed that (1) c-PG reduced the strongest intensity of platelet aggregation and
      the time taken was appropriate, (2) c-PG was the most effective activator to
      reveal the inhibitive effect on platelet by PGI2, cAMP or EDTA, (3) 0.5 - 3 U/ml
      heparin did not significantly change the platelet aggregation induced by c-PG,
      (4) 15 healthy donors' platelet aggregation induced by c-PG displayed clearly on
      the slide until the platelet count below 30 x 10(9)/L, (5) The platelet
      aggregation time induced by c-PG was significantly prolonged in eight patients
      who had taken aspirin. In conclusion, compared to the usual platelet activators,
      c-PG has remarkable potential advantages when used in slide platelet aggregation
      test.

PMID- 15498135
TI  - [Study on the changes of IL-3 and its receptor in mice with immune-mediated
      aplastic anemia].
AB  - The aim of this study was to find new idea for clinical treatment of aplastic
      anemia. Immune-mediated aplastic anemia mice were developed, IL-3 in the
      supernatant with PHA stimulating splenic cells was detected by ELISA, semi
      quantiting analysis of IL-3R was performed by point hybridization. The results
      showed that the IL-3 level in the supernatant with PHA stimulating splenic cells
      of immune-mediated aplastic anemia mice was higher than controls, difference
      between them was significant (P <0.001), while amount of IL-3 receptor by semi
      quantiting analysis was lower than control significantly. In conclusion, the IL-3
      receptor expression level is important for pathogenesis and treatment strategy of
      aplastic anemia.

PMID- 15498136
TI  - [Construction of recombinant vector expressing ALAS2 gene in X-linked
      sideroblastic anemia].
AB  - X-linked sideroblastic anemia (XLSA) is caused by mutations of erythroid-specific
      5-aminolevulinate synthetase (ALAS2) gene. In this study a eukaryotic expression
      vector of ALAS2 was constructed and transfected into eukaryotic cells to observe
      the expression of ALAS2 gene. The full length cDNA of ALAS2 gene was inserted
      into plasmid pDs-red2-N1, named pDs-red2-N1/ALAS2. Then, the vector was
      transfected into K562 cells via electroporation. At 48 hours after transfection,
      total RNA from K562 cells was extracted, expressions of ALAS2 gene and protein
      with red fluorescence in the K562 cells were detected by RT-PCR and flow
      cytometry, respectively. The vector was also transfected into COS 7 cells via
      liposome. Both mRNA and protein expression in COS7 cells were detected by RT-PCR
      and fluorescence microscopy. The result showed that after the pDs-red2-N1/ALAS2
      eukaryotic expression vector was digested by KpnI and BamHI, two fragments of 4
      700 bp and 1 764 bp were displayed by electrophoresis on agarose gel. Sequence
      method confirmed that the sequence was correct. RT-PCR amplified the total RNA
      extracted from the transfected K562 and COS7 cells, and could find mRNA of ALAS2
      gene that can't be found in K562 and COS7 cells usually. The expressions of both
      fluorescein and ALAS2 were significantly increased. The percentage of positive
      cells reached about 19.2% and 10.7%, respectively. ALAS2 expression lasted for 10
      days in COS7 cells and the peak was at the third day. It is concluded that the
      eukaryotic expression vector of ALAS2 gene is successfully constructed; K562 and
      COS7 cells transfected with the vector via electroporation and liposome can
      express ALAS2 protein. So, the vector has the potential in gene replacement and
      can be used for patients with XLSA in future.

PMID- 15498137
TI  - [Time tendency and its cohort study of leukemia mortality of residents in
      Urumqi].
AB  - To explore the distribution of leukemia mortality and its relationship with age
      of residents who live in city Urumqi, data of leukemia mortality of Urumqi
      residents from 1985 years to 2000 years was analysed. On the basis of multiple
      cross-sectional analysis,a cohort study was applied to further analysis. The
      results showed that the total mortality and male's mortality of leukemia in
      Urumqi residents were almost the same as that of national level, while the
      female's mortality of leukemia was lower than that of national level. The cohort
      study showed that mortality of adolescent with leukemia descended with the
      increase of age, but mortality of gerontic leukemia ascended with the increase of
      age. In conclusion, there is a significant relationship between the morbific age
      of leukemia and prognosis of patients with leukemia.

PMID- 15498138
TI  - [Clinical report on treatment of 7 patients with refractory anemia by using
      cyclosporin A].
AB  - To explore the treatment of refractory anemia (RA), 7 cases of myelodysplastic
      syndrome (subtype of refractory anemia) were treated in combination of
      cyclosporin A (CsA) with stanozolol. Duration of treatment with CsA was 5 months
      3 years (mean 13 months). The results showed that among 7 cases 6 were effective,
      1 case no responded to treatment. 3 cases out of 6 effective cases achieved
      complete remission without transfusion dependence, 1 cases achieved partial
      remission, 2 cases were improved. During the investigation signs of leukemia ot
      other malignant tumors not were found in all cases. In conclusion, CsA treatment
      is effective for part cases of RA, side effects of drugs are tolerable for
      patients.

PMID- 15498139
TI  - [Progress on the study of HLA-Cw--review].
AB  - HLA-Cw belongs to classic HLA-I gene, HLA-Cw molecules have high polymorphism
      like HLA-A and B molecules. They distribute extensively on the surfaces of
      karyote, not only presenting endogenetic antigen to CD8+ T cells to induce
      specific killing effect, but also participating in immunologic reaction as the
      ligands of killer cell immunoglobulin-like receptor (KIR). Thus it has been
      valued for their relations to diseases and the functions in transplantation
      immunity, anti virus and anti-tumor immunity.

PMID- 15498140
TI  - [Platelet activation through signal transduction--review].
AB  - Platelet is activated through signal transduction, that mainly includes
      phospholipase-beta (PLCbeta) pathway, protein tyrosine kinases (PTK) pathway,
      phosphatidylinositol3-kinase (PI3-K) pathway, mitogen-activated protein kinases
      (MAPK) pathway, cyclic adenosine monophosphate-protein kinase A (cAMP-PKA)
      pathway and phospholipase A2 (PLA2) pathway. This article focuses on the
      relationship between signal transduction and platelet activation.

PMID- 15498141
TI  - [Progress of studies on VEC apoptosis-inducing proteins in snake venom and its
      mechanism--review].
AB  - Hemorrhagic snake venom specially induces apoptosis of VEC (vascular endothelial
      cells). Five apoptosis-inducing proteins had been purified and characterized from
      crude snake venom. Two of these are L-amino acid oxidase (LAO), the others belong
      to metalloprotease/disintegrin family. LAO catalyzes H2O2 production by oxidizing
      some plasma membrane proteins of VEC, disintegrins interfere with binding of
      integrins with their ligands. The expression of p53 and bcl-2 increases during
      VEC apoptosis induced by snake venom, moreover, the mRNA of bcl-2 is spliced into
      two fragments. It has been proved that one of adhesion-dependent signal
      molecules, alphavbeta3, and one of phospholipid signal molecules, PC-PLC
      (phosphatidylcholine-specific phospholipase C), are involved in above apoptosis
      inducing signal transudation pathway. These results throw light on finding out
      specific component from protein is snake venom. This component is able to induce
      tumor vascular endothelial cells apoptosis. This review summarized progress of
      research on hemorrhagic snake venoms.

PMID- 15498142
TI  - [Resistance mechanism of ST1571 and its prevention research--review].
AB  - STI571 is a new antileukemia agent targeting BCR-ABL tyrosine kinase and
      successfully used in treatment of leukemia patients. Despite strong efficacy of
      the tyrosine kinase inhibitor STI571, resistance has been observed in a
      significant proportion of leukemia patients. This review focuses on the diverse
      mechanisms of ST1571 resistance and its preventive measures.

PMID- 15498143
TI  - [Progress on research and clinical application of interleukin-11 in treatment of
      leukemia--review].
AB  - Interleukin-11 (IL-11) is a multifunctional cytokine that directly acts on
      hematopoietic progenitors, macrophage, T cells, epithelial cells and hepatocytes,
      as well as promotes hematopoiesis, regulates immunity, protects mucosa and
      epithelium, and has the effect of anti-inflammatory. Preclinical and clinical
      studies have demonstrated that IL-11 effectively accelerates the recovery of
      peripheral blood platelets of acute leukemia patients after chemotherapy. In the
      hematopoietic stem cell transplantation, IL-11 prevents and treats the graft
      versus-host disease leading to the effect of graft-versus-leukemia. Synergizing
      with G-CSF, IL-11 mobilizes hematopoietic progenitors and stem cells from bone
      marrow to peripheral blood with higher efficiency. Progress on research and
      clinical application of IL-11 in treatment of leukemia was reviewed in this
      paper.

PMID- 15498144
TI  - Radioimmunotherapy in non-Hodgkin's lymphoma: trials of yttrium 90-labeled
      ibritumomab tiuxetan and beyond.
AB  - The treatment for non-Hodgkin's lymphoma (NHL) has improved over the past 20
      years, but the natural history of the disease has not improved with conventional
      therapeutics. New modalities using targeted therapy based on molecular biology
      and immunology hold promise for better outcomes with less toxicity. Major
      radionuclides available (iodine I 131 and yttrium 90) are discussed and clinical
      trial data with the 90Y-labeled antibody ibritumomab tiuxetan are presented. Long
      term toxicity questions are addressed, the use of dosimetry as a means for
      predicting toxicity is reviewed, and quality-of-life analyses are discussed.
      Radioimmunotherapy represents a safe and effective treatment modality for
      patients with NHL.

PMID- 15498145
TI  - Factors associated with toxicity and response to yttrium 90-labeled ibritumomab
      tiuxetan in patients with indolent non-Hodgkin's lymphoma.
AB  - Treatment of patients with indolent non-Hodgkin's lymphoma (NHL) is evolving.
      These patients usually present with advanced-stage disease. Treatment options for
      patients who experience relapse are limited, and no treatment has been shown to
      be superior to others in improving overall survival of this group of patients,
      with the possible exception of allogeneic stem cell transplantation. Therefore,
      new approaches are needed to improve outcomes in patients with relapsed or
      refractory disease. The anti-CD20 monoclonal antibody, rituximab, was the first
      monoclonal antibody approved for the treatment of indolent B-cell NHL. As a
      single agent in the treatment of relapsed or refractory indolent lymphoma,
      response rates as high as 56% have been observed. This promising new therapy was
      followed by development of radioimmunotherapy, a novel treatment approach that
      combines the targeting capability of monoclonal antibodies with the additional
      cytotoxic effects of radiation. Yttrium 90-labeled ibritumomab tiuxetan (Zevalin)
      is a radiolabeled monoclonal antibody that has been shown to produce clinically
      significant responses in up to 80% of patients with indolent NHL and is the first
      radiolabeled monoclonal antibody approved for therapeutic use in the treatment of
      lymphoma. This article reviews some of the safety and efficacy data for this
      agent in addition to examining factors that could aid in predicting response and
      toxicity in patients with low-grade relapsed or refractory NHL treated with 90Y
      ibritumomab tiuxetan.

PMID- 15498146
TI  - Combining yttrium 90-labeled ibritumomab tiuxetan with high-dose chemotherapy and
      stem cell support in patients with relapsed non-Hodgkin's lymphoma.
AB  - Targeted radioimmunotherapy, including yttrium 90-labeled ibritumomab tiuxetan
      (Zevalin) and iodine I 131 tositumomab (Bexxar), has the potential to increase
      the cure rate for patients with CD20+ B-cell malignancies who are undergoing
      autologous hematopoietic stem cell transplantation. The results of phase I and II
      trials suggest that radioimmunoconjugates can be safely combined with high-dose
      chemotherapy, although the optimal approach remains to be established. This
      review focuses on the use of 90Y ibritumomab tiuxetan combined with high-dose
      chemotherapy in the setting of autologous hematopoietic stem cell
      transplantation.

PMID- 15498147
TI  - Ongoing trials with yttrium 90-labeled ibritumomab tiuxetan in patients with non
      Hodgkin's lymphoma.
AB  - Targeted radiation therapy or radioimmunotherapy has been an important recent
      advance in the treatment of patients with B-cell non-Hodgkin's lymphoma (NHL).
      Yttrium 90-labeled ibritumomab tiuxetan (Zevalin) comprises the murine monoclonal
      antibody ibritumomab, the linker chelator tiuxetan, and the radiolabeled isotope
      yttrium 90. Yttrium 90 ibritumomab tiuxetan has been shown to be efficacious in
      the treatment of B-cell NHL. Initial phase I/II trials established the
      therapeutic dose of ibritumomab tiuxetan for low-grade NHL to be 0.4 mCi/kg, or
      0.3 mCi/kg for patients with mild thrombocytopenia. Currently, there are many
      ongoing trials of ibritumomab tiuxetan with different dose schedules and dose
      intensities in combination with chemotherapy and autologous or allogeneic stem
      cell transplantation in an attempt to improve response rate and duration and to
      study its effectiveness in other B-cell lymphomas including mantle cell lymphoma,
      and chronic lymphocytic leukemia. This article reviews the ongoing trials with
      90Y ibritumomab tiuxetan. Radioimmunotherapy has great promise, and the safe
      incorporation of 90Y ibritumomab tiuxetan into treatment will hopefully result in
      improved survival for patients with NHL.

PMID- 15498148
TI  - New directions in radioimmunotherapy of non-Hodgkin's lymphoma.

PMID- 15498149
TI  - Radiometals as payloads for radioimmunotherapy for lymphoma.
AB  - Because of their remarkable effectiveness in radioimmunotherapy (RIT), 2 anti
      CD20 monoclonal antibody (MAb) drugs, one labeled with indium 111 for imaging or
      yttrium 90 for therapy, and another labeled with iodine I 131 for imaging and
      therapy, have been approved for use in patients with non-Hodgkin's lymphoma
      (NHL). Successful RIT for lymphomas is due in large part to the rapid and
      efficient binding of the targeted MAb to lymphoma cells. Carcinomas are more
      difficult to access, necessitating novel strategies matched with radionuclides
      with specific physical properties. Because there are many radionuclides from
      which to choose, a systematic approach is required to select those preferred for
      a specific application. Thus far, radionuclides with g emissions for imaging and
      particulate emissions for therapy have been investigated. Radionuclides of iodine
      were the first to be used for RIT. Many conventionally radioiodinated MAbs are
      degraded after endocytosis by target cells, releasing radioiodinated peptides and
      amino acids. In contrast, radiometals have been shown to have residualizing
      properties, advantageous when the MAb is localized in malignant tissue. b
      emitting lanthanides like those of 90Y, lutetium 177, etc. have attractive
      combinations of biologic, physical, radiochemical, production, economic, and
      radiation safety characteristics. Other radiometals, such as copper-67 and copper
      64, are also of interest. a-emitters, including actinium-225 and bismuth-213,
      have been used for therapy in selected applications. Evidence for the impact of
      the radionuclide is provided by data from the randomized pivotal phase III trial
      of 90Y ibritumomab tiuxetan (Zevalin) in patients with NHL; responses were about
      2 times greater in the 90Y ibritumomab tiuxetan arm than in the rituximab arm. It
      is clear that RIT has emerged as a safe and efficient method for treatment of
      NHL, especially in specific settings.

PMID- 15498151
TI  - New measurable indicator for tuberculosis case detection.
AB  - The World Health Organization's goal for tuberculosis (TB) control is to detect
      70% of new, smear-positive TB cases and cure 85% of these cases. The case
      detection rate is the number of reported cases per 100,000 persons per year
      divided by the estimated incidence rate per 100,000 per year. TB incidence is
      uncertain and not measured but estimated; therefore, the case detection rate is
      uncertain. This article proposes a new indicator to assess case detection: the
      patient diagnostic rate. The patient diagnostic rate is the rate at which
      prevalent cases are detected by control programs and can be measured as the
      number of reported cases per 100,000 persons per year divided by the prevalence
      per 100,000. Prevalence can be measured directly through national prevalence
      surveys. Conducting prevalence surveys at 5- to 10-year intervals would allow
      countries with high rates of disease to determine their case detection
      performance by using the patient diagnostic rate and determine the effect of
      control measures.

PMID- 15498152
TI  - Potential public health impact of new tuberculosis vaccines.
AB  - Developing effective tuberculosis (TB) vaccines is a high priority. We use
      mathematical models to predict the potential public health impact of new TB
      vaccines in high-incidence countries. We show that preexposure vaccines would be
      almost twice as effective as postexposure vaccines in reducing the number of new
      infections. Postexposure vaccines would initially have a substantially greater
      impact, compared to preexposure vaccines, on reducing the number of new cases of
      disease. However, the effectiveness of postexposure vaccines would diminish over
      time, whereas the effectiveness of preexposure vaccines would increase. Thus,
      after 20 to 30 years, post- or preexposure vaccination campaigns would be almost
      equally effective in terms of cumulative TB cases prevented. Even widely deployed
      and highly effective (50%-90% efficacy) pre- or postexposure vaccines would only
      be able to reduce the number of TB cases by one third. We discuss the health
      policy implications of our analyses.

PMID- 15498153
TI  - Deaths due to unknown foodborne agents.
AB  - This study reviews the available evidence on unknown pathogenic agents
      transmitted in food and examines the methods that have been used to estimate that
      such agents cause 3,400 deaths per year in the United States. The estimate of
      deaths was derived from hospital discharge and death certificate data on deaths
      attributed to gastroenteritis of unknown cause. Fatal illnesses due to unknown
      foodborne agents do not always involve gastroenteritis, and gastroenteritis may
      not be accurately diagnosed or reported on hospital charts or death certificates.
      The death estimate consequently omitted deaths from unknown foodborne agents that
      do not cause gastroenteritis and likely overstated the number of deaths from
      agents that cause gastroenteritis. Although the number of deaths from unknown
      foodborne agents is uncertain, the possible economic cost of these deaths is so
      large that increased efforts to identify the causal agents are warranted.

PMID- 15498154
TI  - Laboratory exposures to staphylococcal enterotoxin B.
AB  - Staphylococcal enterotoxins are 23- to 29-kDa polypeptides in the bacterial
      superantigen protein family. Clinical symptoms from intoxication with
      staphylococcal enterotoxins vary by exposure route. Ingestion results in
      gastrointestinal symptoms, and inhalation results in fever as well as pulmonary
      and gastrointestinal symptoms. Review of occupational exposures at the U.S. Army
      Medical Research Institute of Infectious Diseases from 1989 to 2002 showed that
      three laboratory workers had symptoms after ocular exposure to staphylococcal
      enterotoxin B (SEB). Conjunctivitis with localized cutaneous swelling occurred in
      three persons within 1 to 6 hours after exposure to SEB; two of these persons
      also had gastrointestinal symptoms, which suggests that such symptoms occurred as
      a result of exposure by an indirect cutaneous or ocular route. Ocular exposures
      from SEB resulting in conjunctivitis and localized swelling have not previously
      been reported. Symptoms from these patients and review of clinical symptoms of 16
      laboratory-acquired inhalational SEB intoxications may help healthcare workers
      evaluate and identify SEB exposures in laboratory personnel at risk.

PMID- 15498155
TI  - Viral loads in clinical specimens and SARS manifestations.
AB  - A retrospective viral load study was performed on clinical specimens from 154
      patients with laboratory-confirmed severe acute respiratory syndrome (SARS); the
      specimens were prospectively collected during patients' illness. Viral load in
      nasopharyngeal aspirates (n = 142) from day 10 to day 15 after onset of symptoms
      was associated with oxygen desaturation, mechanical ventilation, diarrhea,
      hepatic dysfunction, and death. Serum viral load (n = 53) was associated with
      oxygen desaturation, mechanical ventilation, and death. Stool viral load (n = 94)
      was associated with diarrhea, and urine viral load (n = 111) was associated with
      abnormal urinalysis results. Viral replications at different sites are important
      in the pathogenesis of clinical and laboratory abnormalities of SARS.

PMID- 15498156
TI  - SARS antibody test for serosurveillance.
AB  - A peptide-based enzyme-linked immunosorbent assay (ELISA) can be used for
      retrospective serosurveillance of severe acute respiratory syndrome (SARS) by
      helping identify undetected chains of disease transmission. The assay was
      developed by epitope mapping, using synthetic peptides from the spike, membrane,
      and nucleocapsid protein sequences of SARS-associated coronavirus. The new
      peptide ELISA consistently detected seroconversion by week 2 of onset of fever,
      and seropositivity remained through day 100. Specificity was 100% on normal blood
      donor samples, on serum samples associated with infection by other pathogens, and
      on an interference panel. The peptide-based test has advantages of safety,
      standardization, and automation over previous immunoassays for SARS. The assay
      was used for a retrospective survey of healthy healthcare workers in Taiwan who
      treated SARS patients. Asymptomatic seroconversions were detected in two
      hospitals that had nosocomial disease.

PMID- 15498157
TI  - Experimental infection of ground squirrels (Spermophilus tridecemlineatus) with
      monkeypox virus.
AB  - A proposed new small-animal (rodent) model for studying the pathogenesis and
      treatment of severe orthopoxvirus infections is described. Thirteen-lined ground
      squirrels (Spermophilus tridecemlineatus) were infected intraperitoneally and
      intranasally with monkeypox virus (MPXV). A fulminant illness developed in all
      animals, and they died 6-9 days after infection. Virus was cultured from the
      blood and oropharynx several days before death; at necropsy, all of the organs
      tested contained relatively high titers of MPXV. The major pathologic findings
      were in the liver, which showed centrilobular necrosis, steatosis, and basophilic
      inclusion bodies in hepatocytes. Splenic necrosis was also observed, as well as
      interstitial inflammation in the lungs. The pathologic features of MPXV in ground
      squirrels are similar to that described with MPXV in macaques and severe variola
      (smallpox) virus infection in humans.

PMID- 15498158
TI  - Silent nucleotide polymorphisms and a phylogeny for Mycobacterium tuberculosis.
AB  - Much remains unknown of the phylogeny and evolution of Mycobacterium
      tuberculosis, an organism that kills 2 million people annually. Using a
      population-based approach that analyzes multiple loci around the chromosome, we
      demonstrate that neutral genetic variation in genes associated with antimicrobial
      drug resistance has sufficient variation to construct a robust phylogenetic tree
      for M. tuberculosis. The data describe a clonal population with a minimum of four
      distinct M. tuberculosis lineages, closely related to M. bovis. The lineages are
      strongly geographically associated. Nucleotide substitutions proven to cause drug
      resistance are distributed throughout the tree, whereas nonsynonymous base
      substitutions unrelated to drug resistance have a restricted distribution. The
      phylogenetic structure is concordant with all the previously described genotypic
      and phenotypic groupings of M. tuberculosis strains and provides a unifying
      framework for both epidemiologic and evolutionary analysis of M. tuberculosis
      populations.

PMID- 15498159
TI  - Genetic divergence and dispersal of yellow fever virus, Brazil.
AB  - An analysis of 79 yellow fever virus (YFV) isolates collected from 1935 to 2001
      in Brazil showed a single genotype (South America I) circulating in the country,
      with the exception of a single strain from Rondonia, which represented South
      America genotype II. Brazilian YFV strains have diverged into two clades; an
      older clade appears to have become extinct and another has become the dominant
      lineage in recent years. Pairwise nucleotide diversity between strains ranged
      from 0% to 7.4%, while amino acid divergence ranged from 0% to 4.6%. Phylogenetic
      analysis indicated traffic of virus variants through large geographic areas and
      suggested that migration of infected people may be an important mechanism of
      virus dispersal. Isolation of vaccine virus from a patient with a fatal case
      suggests that vaccine-related illness may have been misdiagnosed in the past.

PMID- 15498160
TI  - Genotyping, Orientalis-like Yersinia pestis, and plague pandemics.
AB  - Three pandemics have been attributed to plague in the last 1,500 years. Yersinia
      pestis caused the third, and its DNA was found in human remains from the second.
      The Antiqua biovar of Y. pestis may have caused the first pandemic; the other two
      biovars, Medievalis and Orientalis, may have caused the second and third
      pandemics, respectively. To test this hypothesis, we designed an original
      genotyping system based on intergenic spacer sequencing called multiple spacer
      typing (MST). We found that MST differentiated every biovar in a collection of 36
      Y. pestis isolates representative of the three biovars. When MST was applied to
      dental pulp collected from remains of eight persons who likely died in the first
      and second pandemics, this system identified original sequences that matched
      those of Y. pestis Orientalis. These data indicate that Y. pestis caused cases of
      Justinian plague. The two historical plague pandemics were likely caused by
      Orientalis-like strains.

PMID- 15498162
TI  - Foodborne botulism in the Republic of Georgia.
AB  - Foodborne botulism is a potentially fatal, paralytic illness that can cause large
      outbreaks. A possible increase in botulism incidence during 2001 in the Republic
      of Georgia prompted this study. We reviewed surveillance data and abstracted
      records of patients with botulism who were hospitalized from 1980 to 2002. During
      this period, 879 botulism cases were detected. The median annual incidence
      increased from 0.3 per 100,000 during 1980 to 1990 to 0.9 per 100,000 during 1991
      to 2002. For 706 botulism patients hospitalized from 1980 to 2002, 80% of their
      cases were attributed to home-preserved vegetables. Surveillance evaluation
      verified that botulism incidence varied greatly by region. Georgia has the
      highest nationally reported rate of foodborne botulism in the world. A strategy
      addressing individual behaviors in the home is needed to improve food safety;
      developing this strategy requires a deeper understanding of why botulism has
      increased and varies by region.

PMID- 15498161
TI  - Rotavirus serotype G9P[8] and acute gastroenteritis outbreak in children,
      Northern Australia.
AB  - During 2001, an outbreak of severe acute gastroenteritis swept through Central
      and northern Australia and caused serious disruption to health services. We
      tracked and characterized the rotavirus strain implicated in the outbreak.
      Comparison of the electropherotypes of outbreak samples suggested that one G9P[8]
      strain was likely responsible for the outbreak. Samples were obtained from
      geographically distinct regions of Australia where the epidemic had occurred. The
      outbreak strains showed identical nucleotide sequences in genes encoding three
      rotavirus proteins, VP7, VP8, and NSP4, but they were distinct from G9P[8]
      strains isolated in previous years. Several of the amino acid substitutions on
      the VP7 and NSP4 proteins were identified in regions known to influence function
      and may have contributed to the emergence and increased dominance of the outbreak
      strains. Rotavirus serotype surveillance should continue with methods capable of
      identifying new and emerging types.

PMID- 15498163
TI  - Foodborne botulism in the United States, 1990-2000.
AB  - Foodborne botulism, a potentially lethal neuroparalytic disease, is caused by
      ingesting preformed Clostridium botulinum neurotoxin. We reviewed surveillance
      data and reports from 1990 to 2000. Of 263 cases from 160 foodborne botulism
      events (episode of one or more related cases) in the United States, 103 (39%)
      cases and 58 events occurred in Alaska. Patients' median age was 48 years; 154
      (59%) were female; the case-fatality rate was 4%. The median number of cases per
      event was 1 (range 1-17). Toxin type A caused 51% of all cases; toxin type E
      caused 90% of Alaska cases. A particular food was implicated in 126 (79%) events.
      In the lower 49 states, a noncommercial food item was implicated in 70 (91%)
      events, most commonly home-canned vegetables (44%). Two restaurant-associated
      outbreaks affected 25 persons. All Alaska cases were attributable to traditional
      Alaska Native foods. Botulism prevention efforts should be focused on those who
      preserve food at home, Alaska Natives, and restaurant workers.

PMID- 15498164
TI  - Computer algorithms to detect bloodstream infections.
AB  - We compared manual and computer-assisted bloodstream infection surveillance for
      adult inpatients at two hospitals. We identified hospital-acquired, primary,
      central-venous catheter (CVC)-associated bloodstream infections by using five
      methods: retrospective, manual record review by investigators; prospective,
      manual review by infection control professionals; positive blood culture plus
      manual CVC determination; computer algorithms; and computer algorithms and manual
      CVC determination. We calculated sensitivity, specificity, predictive values,
      plus the kappa statistic (kappa) between investigator review and other methods,
      and we correlated infection rates for seven units. The kappa value was 0.37 for
      infection control review, 0.48 for positive blood culture plus manual CVC
      determination, 0.49 for computer algorithm, and 0.73 for computer algorithm plus
      manual CVC determination. Unit-specific infection rates, per 1,000 patient days,
      were 1.0-12.5 by investigator review and 1.4-10.2 by computer algorithm
      (correlation r = 0.91, p = 0.004). Automated bloodstream infection surveillance
      with electronic data is an accurate alternative to surveillance with manually
      collected data.

PMID- 15498165
TI  - Space-time cluster analysis of invasive meningococcal disease.
AB  - Clusters are recognized when meningococcal cases of the same phenotypic strain
      (markers: serogroup, serotype, and subtype) occur in spatial and temporal
      proximity. The incidence of such clusters was compared to the incidence that
      would be expected by chance by using space-time nearest-neighbor analysis of
      4,887 confirmed invasive meningococcal cases identified in the 9-year
      surveillance period 1993-2001 in the Netherlands. Clustering beyond chance only
      occurred among the closest neighboring cases (comparable to secondary cases) and
      was small (3.1%, 95% confidence interval 2.1%-4.1%).

PMID- 15498166
TI  - Methicillin-resistant Staphylococcus aureus in Europe, 1999-2002.
AB  - We explored the variation in proportions of methicillin-resistant Staphylococcus
      aureus (MRSA) between and within countries participating in the European
      Antimicrobial Resistance Surveillance System and temporal trends in its
      occurrence. This system collects routine antimicrobial susceptibility tests for
      S. aureus. We examined data collected from January 1999 through December 2002
      (50,759 isolates from 495 hospitals in 26 countries). MRSA prevalence varied
      almost 100-fold, from <1% in northern Europe to >40% in southern and western
      Europe. MRSA proportions significantly increased in Belgium, Germany, Ireland,
      the Netherlands, and the United Kingdom, and decreased in Slovenia. Within
      countries, MRSA proportions varied between hospitals with highest variance in
      countries with a prevalence of 5% to 20%. The observed trends should stimulate
      initiatives to control MRSA at national, regional, and hospital levels. The large
      differences between hospitals indicate that efforts may be most effective at
      regional and hospital levels.

PMID- 15498167
TI  - Outbreak of hantavirus pulmonary syndrome, Los Santos, Panama, 1999-2000.
AB  - An outbreak of hantavirus pulmonary syndrome occurred in the province of Los
      Santos, Panama, in late 1999 and early 2000. Eleven cases were identified; 9 were
      confirmed by serology. Three cases were fatal; however, no confirmed case-patient
      died. Case-neighborhood serologic surveys resulted in an overall hantavirus
      antibody prevalence of 13% among household and neighborhood members from the
      outbreak foci. Epidemiologic investigations did not suggest person-to-person
      transmission of hantavirus infection. By use of Sin Nombre virus antigen,
      hantavirus antibodies were detected in Oligoryzomys fulvescens and Zygodontomys
      brevicauda cherriei. This outbreak resulted in the first documented cases of
      human hantavirus infections in Central America.

PMID- 15498168
TI  - Detection of Anaplasma phagocytophilum DNA in Ixodes ticks (Acari: Ixodidae) from
      Madeira Island and Setubal District, mainland Portugal.
AB  - A total of 278 Ixodes ticks, collected from Madeira Island and Setubal District,
      mainland Portugal, were examined by polymerase chain reaction (PCR) for the
      presence of Anaplasma phagocytophilum. Six (4%) of 142 Ixodes ricinus nymphs
      collected in Madeira Island and 1 nymph and 1 male (2%) of 93 I. ventalloi
      collected in Setubal District tested positive for A. phagocytophilum msp2 genes
      or rrs. Infection was not detected among 43 I. ricinus on mainland Portugal. All
      PCR products were confirmed by nucleotide sequencing to be identical or to be
      most closely related to A. phagocytophilum. To our knowledge, this is the first
      evidence of A. phagocytophilum in ticks from Setubal District, mainland Portugal,
      and the first documentation of Anaplasma infection in I. ventalloi. Moreover,
      these findings confirm the persistence of A. phagocytophilum in Madeira Island's
      I. ricinus.

PMID- 15498169
TI  - Year-round West Nile virus activity, Gulf Coast region, Texas and Louisiana.
AB  - West Nile virus (WNV) was detected in 11 dead birds and two mosquito pools
      collected in east Texas and southern Louisiana during surveillance studies in the
      winter of 2003 to 2004. These findings suggest that WNV is active throughout the
      year in this region of the United States.

PMID- 15498170
TI  - SARS-CoV antibody prevalence in all Hong Kong patient contacts.
AB  - A total of 1,068 asymptomatic close contacts of patients with severe acute
      respiratory (SARS) from the 2003 epidemic in Hong Kong were serologically tested,
      and 2 (0.19%) were positive for SARS coronavirus immunoglobulin G antibody. SARS
      rarely manifests as a subclinical infection, and at present, wild animal species
      are the only important natural reservoirs of the virus.

PMID- 15498171
TI  - Yellow fever virus infectivity for Bolivian Aedes aegypti mosquitoes.
AB  - The absence of urban yellow fever virus (YFV) in Bolivian cities has been
      attributed to the lack of competent urban mosquito vectors. Experiments with
      Aedes aegypti from Santa Cruz, Bolivia, demonstrated infection (100%),
      dissemination (20%), and transmission of a Bolivian YFV strain (CENETROP-322).

PMID- 15498172
TI  - Typing of Borrelia relapsing fever group strains.
AB  - Partial sequencing of the 16S-23S rDNA intergenic spacer showed two to four
      genotypes each for Borrelia hermsii and B. turicatae, both relapsing fever agents
      transmitted by argasid ticks, and for B. miyamotoi and B. lonestari, transmitted
      by ixodid ticks. Field surveys of Ixodes ticks in Connecticut and Sweden showed
      limited local diversity for B. miyamotoi.

PMID- 15498173
TI  - Salmonella enterica serotype Uganda infection in New York City and Chicago.
AB  - Outbreaks associated with distinct strains of Salmonella enterica serotype
      Uganda, a rare serotype, occurred in New York City and Chicago during the summer
      of 2001. Both outbreaks were linked to eating ready-to-eat pork products. This
      serotype may emerge as a more frequent cause of human infections.

PMID- 15498174
TI  - Yellow fever outbreak, southern Sudan, 2003.
AB  - In May 2003, an outbreak of fatal hemorrhagic fever, caused by yellow fever
      virus, occurred in southern Sudan. Phylogenetic analysis showed that the virus
      belonged to the East African genotype, which supports the contention that yellow
      fever is endemic in East Africa with the potential to cause large outbreaks in
      humans.

PMID- 15498175
TI  - Acinetobacter baumannii in human body louse.
AB  - While we were isolating Bartonella quintana from body lice, 40 Acinetobacter
      baumannii strains were also isolated and genotyped. One clone was unique and the
      other was ampicillin susceptible. A. baumannii DNA was later detected in 21% of
      622 lice collected worldwide. These findings show an A. baumannii epidemic in
      human body lice.

PMID- 15498176
TI  - Fluoroquinolone resistance in Salmonella enterica serotype Choleraesuis, Taiwan,
      2000-2003.
AB  - Salmonella enterica serotype Choleraesuis is a highly invasive pathogen that
      infects humans and causes systemic infections that require antimicrobial therapy.
      Surveillance in Taiwan showed that fluoroquinolone resistance in S. Choleraesuis
      markedly increased from 2000 to 2003, reaching approximately 70% in 2003.

PMID- 15498177
TI  - Barriers to Creutzfeldt-Jakob disease autopsies, California.
AB  - Creutzfeldt-Jakob disease (CJD) surveillance relies on autopsy and
      neuropathologic evaluation. The 1990-2000 CJD autopsy rate in California was 21%.
      Most neurologists were comfortable diagnosing CJD (83%), but few pathologists
      felt comfortable diagnosing CJD (35%) or performing autopsy (29%). Addressing
      obstacles to autopsy is necessary to improve CJD surveillance.

PMID- 15498178
TI  - Leishmaniasis in refugee and local Pakistani populations.
AB  - The epidemiology of anthroponotic cutaneous leishmaniasis was investigated in
      northwest Pakistan. Results suggested similar patterns of endemicity in both
      Afghan refugee and Pakistani populations and highlighted risk factors and
      household clustering of disease.

PMID- 15498179
TI  - Botulism type E outbreak associated with eating a beached whale, Alaska.
AB  - We report an outbreak of botulism that occurred in July 2002 in a group of 12
      Alaskan Yu'pik Eskimos who ate blubber and skin from a beached beluga whale.
      Botulism death rates among Alaska Natives have declined in the last 20 years, yet
      incidence has increased.

PMID- 15498180
TI  - [Current concept of polycystic ovary syndrome].

PMID- 15498181
TI  - [Summary of the national symposium on polycystic ovary syndrome].

PMID- 15498182
TI  - [Correlation between single nucleotide polymorphism of insulin receptor gene with
      polycystic ovary syndrome].
AB  - OBJECTIVE: To investigate the correlation of C/T single nucleotide polymorphism
      at exon 17 in tyrosine kinase domain of insulin receptor gene with polycystic
      ovary syndrome (PCOS). METHODS: One hundred and twenty patients with PCOS (PCOS
      group) and 40 normal females (control group) were included and the 1058 site
      single nucleotide polymorphism at exon 17 of insulin receptor gene (INSR) was
      detected with polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP). The baseline parameters including levels of serum follicular
      stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), estradiol
      (E(2)), testosterone (T) and lipid, as well as the body mass index (BMI) and
      waist/hip ratio (WHR) were measured. Glucose tolerance and insulin releasing
      before and after loading with 75 g of glucose were also assayed. RESULTS: (1) BMI
      (25 +/- 4 vs. 23 +/- 3, P < 0.01), WHR (0.82 +/- 0.06 vs. 0.79 +/- 0.07, P <
      0.05), LH [(9.2 +/- 6.1) U/L vs. (4.4 +/- 1.6) U/L, P < 0.01], T [(1.9 +/- 0.9)
      nmol/L vs. (1.0 +/- 0.6) nmol/L, P < 0.01] and E(2) [(205 +/- 119) pmol/L vs.
      (143 +/- 75) pmol/L, P < 0.01] of PCOS group were higher than those of control
      group. (2) The blood sugar and insulin levels of fasting, 30 min, 60 min, 120 min
      after glucose loading in obese PCOS (BMI >/= 25 kg/m(2)) were significantly
      higher than those in the non-obese PCOS (BMI < 25 kg/m(2)). (3) C/T single
      nucleotide polymorphism frequency at exon 17 of INSR in patients with PCOS was
      significantly higher than that in normal female (41% vs. 12.5%, P < 0.01). There
      was a significant difference between the frequency in non-obese PCOS (52.2%) and
      obese PCOS (25.5%, P < 0.01). (4) BMI in patients with T allele 23 +/- 3 of INSR
      single nucleotide polymorphism was lower than that with C allele (26 +/- 4, P <
      0.05). CONCLUSIONS: (1) The body weight and gene single nucleotide polymorphism
      of INSR may play an important role in the occurrence of insulin resistance in
      patients with PCOS. (2) The 1058 site nucleotide polymorphism of insulin receptor
      gene is one of the susceptibility genes in patients with PCOS, especially in non
      obese PCOS patients.

PMID- 15498183
TI  - [Clinical study on treating insulin resistance and promoting ovulation in
      polycystic ovary syndrome].
AB  - OBJECTIVE: To investigate the effects of metformin and clomiphene on infertility
      caused by polycystic ovary syndrome (PCOS) with insulin-resistance (IR) and to
      observe the effects of metformin on PCOS with pseudoacanthosis nigricans (AN) and
      IR. METHODS: Seventy infertility patients caused by PCOS with IR were randomly
      divided into three groups : patients in group Aa (n = 20) took metformin 500 mg
      only, three times daily for 3 months; patients in group Ab (n = 20) took
      clomiphene 50 mg only, once daily from the 5th day of menstrual cycle or
      withdrawal bleeding for 5 days and 3 cycles, and patients in group Ac (n = 30)
      were treated by metformin and clomiphene for 3 cycles, with the same dosages as
      groups Aa and Ab. Thirty patients who suffered from PCOS with AN and IR were
      served as group B, They took metformin only, the same as group Aa. The following
      indexes were measured before and after three months or cycles of treatment in all
      the patients: body height, weight, waistline, hipline, body mass index (BMI),
      waist hip ratio (WHR), fasting insulin (FINS), fasting blood-glucose (FBG), total
      cholesterol (TC), triglyceride (TG), and sex hormones [follicle-stimulating
      hormone (FSH), luteotropic hormone (LH), prolactin (PRL), estradiol (E(2)),
      progestin (P), testosterone (T)]. RESULTS: The pregnant rate was 15% (group Aa),
      20% (group Ab), and 57% (group Ac) respectively. It was significantly higher in
      group Ac than in groups Aa and Ab, (P < 0.01), while there was no significant
      difference between the latter two groups (P > 0.05). In group Ac the pretreatment
      levels of FINS, BMI, T, TG, and TC were (49.7 +/- 6.4) mU/L, 29.4 +/- 2.2, (6.4
      +/- 2.2) nmol/L, (4.1 +/- 1.0) mmol/L, (6.3 +/- 0.5) mmol/L, and posttreatment
      levels were (27.7 +/- 1.8) mU/L, 23.6 +/- 5.2, (3.8 +/- 2.0) nmol/L, (2.2 +/-
      0.7) mmol/L, (4.6 +/- 0.5) mmol/L. In group Aa pretreatment levels of FINS, BMI,
      T, TG, and TC were (50.0 +/- 8.2) mU/L, 28.7 +/- 1.2, (6.4 +/- 2.0) nmol/L, (4.3
      +/- 1.2) mmol/L, (6.6 +/- 0.3) mmol/L, and posttreatment levels were (29.9 +/-
      8.2) mU/L, 22.4 +/- 9.3, (4.3 +/- 0.9) nmol/L, (2.3 +/- 0.3) mmol/L, (4.8 +/-
      0.6) mmol/L. In group B pretreatment levels of FINS, BMI, T, TG, and TC were
      (51.0 +/- 8.1) mU/L, 29.8 +/- 3.1, (6.3 +/- 3.5) nmol/L, (4.5 +/- 1.2) mmol/L,
      (6.8 +/- 0.2) mmol/L, and posttreatment levels were (28.5 +/- 2.8) mU/L, 23.4 +/-
      6.1, (3.0 +/- 0.9) nmol/L, (2.3 +/- 0.9) mmol/L, (5.0 +/- 0.6) mmol/L. In groups
      Ac, Aa and B, the IR condition was obviously improved and posttreatment serum
      levels of T, TG, TC, FINS and BMI were significantly lower than those of
      pretreatment (all P < 0.01). In group Ab pretreatment levels of FINS, BMI, T, TG,
      and TC were (48.8 +/- 7.4) mU/L, 27.3 +/- 2.8, (6.0 +/- 2.0) nmol/L, (3.9 +/-
      1.4) mmol/L, (6.4 +/- 0.6) mmol/L, and posttreatment levels were (42.9 +/- 7.0)
      mU/L, 27.5 +/- 3.1, (4.0 +/- 2.4) nmol/L, (3.9 +/- 0.3) mmol/L, (5.9 +/- 0.3)
      mmol/L, (all P > 0.05). Among patients in group B, 90% (27/30) menstrual
      condition and ovulation function were improved and AN was reduced in different
      degree after three months' treatment. CONCLUSION: Metformin can increase the
      sensitivity of PCOS to clomiphene and improve ovulation function of clomiphene.
      Metformin plus clomiphene is an effective way of treating infertility caused by
      PCOS with IR.

PMID- 15498184
TI  - [Correlation between local hormones and CD36 transcription level in women with
      polycystic ovary].
AB  - OBJECTIVE: To detect CD(36) expressions in polycystic ovary (PCO), and to explore
      its correlation with local androgen and insulin at transcription level. METHODS:
      From August 2002 to February 2003, 12 patients with asymmetric PCO, 15 primary or
      secondary infertile patients without endocrine disorders and 8 polycystic ovary
      syndrome (PCOS) with bilateral PCO were recruited. Extraction of follicular fluid
      and detection of testosterone (T), dehydroepiandrosterone sulfate (DHEAS),
      insulin (INS) and androstenedione (A(2)) were performed. Relative CD(36) mRNA
      expression level of human ovarian inner thecal cells was analyzed by auto image
      analysis system (IAS) after RT-PCR. RESULTS: The level of CD(36) mRNA expression
      in thecal cells was 0.24 +/- 0.07 in polycystic ovary of PCO group and 0.21 +/-
      0.05 in bilateral ovaries of PCOS group, respectively, which were significantly
      lower than 0.83 +/- 0.13 in normal ovaries (P < 0.01). T and INS levels of
      follicle fluid in PCO were significantly higher than that in normal ovaries (P <
      0.01). T and INS levels of follicle fluid were negatively related to CD(36) mRNA
      expression of follicular theca interna (r = -0.6810, r = -0.6708, P < 0.01).
      CONCLUSION: Decrease of scavenger receptor gene CD(36) mRNA may play a role in
      the pathogenesis of PCO by increasing the level of T and INS in follicular fluid.

PMID- 15498185
TI  - [Ultrasound criterion for the diagnosis of polycystic ovary syndrome: ovarian
      stroma/total area ratio].
AB  - OBJECTIVE: To evaluate the diagnostic value of ultrasound parameters of ovarian
      stroma area (S), total ovarian area (A) and S/A ratio for polycystic ovarian
      syndrome (PCOS). METHODS: The A, S and S/A ratio were determined by use of
      transvaginal pelvic ultrasound, and serum levels of follicle stimulating hormone
      (FSH), luteinizing hormone (LH) and testosterone (T) were assayed in 58 PCOS
      patients and 60 controls. Of 58 PCOS patients, 32 underwent hyperinsulinemic
      euglycemic clamp technique (HGCT). RESULTS: Patients with PCOS showed
      significantly higher ovarian S and S/A ratio when compared to the control groups
      (P = 0.045, P = 0.001, respectively). S/A ratio and S were significantly related
      to HGCT results and T. CONCLUSION: The S/A ratio and S are of value in diagnosis
      of PCOS.

PMID- 15498186
TI  - [Epithelial ovarian tumors in adolescence: a study of clinical features and
      treatment].
AB  - OBJECTIVE: To study the clinical feature, diagnosis and treatment of epithelial
      ovarian tumors in adolescent patients. METHODS: A retrospective analysis was
      performed on 29 patients of epithelial ovarian tumors between the age of 13 and
      19 during the period of 1983 - 2002 in Peking Union Medical College Hospital.
      Twenty of the cases were with benign tumors, four with borderline, and five with
      malignant tumors. RESULTS: The average age was 16.5 years old. The majority of
      patients presented with abdominal pain, abdominal distention and a large pelvic
      mass. The histological types included mucinous tumor in twenty-two cases, serous
      tumor in six, and endometroid tumor in one case. Among the nine cases with
      borderline or malignant tumors, eight were at stage I and one at stage IIIc. Of
      benign tumor group, an abdominal unilateral salpingo-oophorectomy was performed
      on nine cases. A laparoscopic cystectomy was undertaken in 11 patients. The nine
      cases with borderline or malignant tumors underwent cytoreductive surgery and
      comprehensive staging surgery; fertility was preserved for eight of them. A
      cisplatin combined chemotherapy was given to four patients with malignant tumors.
      All of the patients were without evidence of disease recurrence during the follow
      up. CONCLUSIONS: The incidence of epithelial ovarian tumors during adolescence
      increases with age. Mucinous tumor is the most common histological type in
      adolescent patients. A laparoscopic cystectomy could be considered for most
      benign patients. The therapeutic strategy should be individualized, and surgical
      approach should consider both cure and preservation of fertility in malignant
      cases.

PMID- 15498187
TI  - [Multidisciplinary treatment of recurrent epithelial ovarian carcinoma and
      prognostic analysis].
AB  - OBJECTIVE: To investigate individualized and multi-phase management of recurrent
      epithelial ovarian carcinoma in order to improve survival of the patients.
      METHODS: From 1998 to 2002, 70 patients with recurrent epithelial ovarian
      carcinoma were enrolled in the present study. The treatments were divided into:
      (1) Induction of tumor remission: platinum sensitive patients were treated with
      paclitaxol + cisplatin (TP) or carboplatin + cyclophosphamide (CP) regimen;
      platinum resistant patients used Taxol + mitomycin (TM) or etoposide + mitomycin
      (VM) regimen. Resection of tumors was done in an attempt to reduce the residual
      tumor with a diameter less than 1 cm. Local radiotherapy was performed for those
      with residual tumor and who achieved clinical response after chemotherapy or
      surgery. (2) Consolidation therapy: chemotherapy with lower doses was
      administrated after disease remission. Interferon was used as immunotherapy
      during chemotherapy and radiotherapy. Survival analysis was done. RESULTS: (1)
      The 1, 2, 3, 4, 5-year survival rates were 67%, 51%, 45%, 38%, 32%. Median
      survival was 38.57 months. (3) The 1, 2, 3-year progression-free survival rates
      of the research arm were 41%, 37%, 24%. Median progression-free survival was
      12.00 months. (4) Multivariate analysis revealed that platinum-free interval (P <
      0.05), Karnofsky performance scale (P < 0.01), residual disease (P < 0.01) and
      courses of second-line chemotherapy (P < 0.05) were independent prognostic
      factors. Residual disease (P < 0.05) and courses of second-line chemotherapy (P <
      0.01) contributed to progression-free survival. CONCLUSIONS: Individualized and
      multi-phase treatment of recurrent epithelial ovarian carcinoma is efficacious.
      Optimal second cytoreduction and second-line chemotherapy are beneficial to
      improve the survival.

PMID- 15498188
TI  - [Effects of Spasfon on course of labor].
AB  - OBJECTIVE: To observe the effects of Spasfon on improving dilatation of cervix
      and promoting the progression of labor. METHODS: Ninety seven normal primiparae
      with cervical edema were randomly divided into Spasfon group (group A, n = 46)
      and atropine group (group B, n = 51) when the cervix dilated 2 - 3 cm. Group A
      was given 80 mg of Spasfon intravenously, and group B was injected atropine 0.5
      mg into the cervix. RESULTS: (1) The mean time period from drug administration to
      full dilation of the cervix was (3.1 +/- 0.3) h in group A, and (4.4 +/- 0.4) h
      in group B (P < 0.01). (2) The disappearance ratio of cervical edema 2 h after
      drug administration in group A was 95.6%, while in group B it was 90.2% (P >
      0.05); the mean dilatation of cervix between the 2 hours in group A was (4.3 +/-
      0.2) cm, while in group B it was (2.5 +/- 0.3) cm (P < 0.01). (3) There were no
      obvious side effects in group A. While eight women in group B complained of
      thirst and 22 women had increased heart rate accompanied with elevated baseline
      FHR, which all recovered in about 60 minutes. (4) Vaginal delivery rate in group
      A was 95.7%, and 90.2% in group B (P > 0.05). (5) There was no statistically
      significant difference in the color of amniotic fluid, suffocation state and
      weight of the newborns between the two groups (P > 0.05). (6) There was no
      statistically significant difference in postpartum hemorrhage between the two
      groups, either (P > 0.05). CONCLUSION: Spasfon can effectively improve cervical
      dilatation during labor and it is well tolerated by both mother and newborn.

PMID- 15498189
TI  - [Relationship between expression of vimentin, type IV collagen and fibronectin in
      human placenta and pregnancy induced hypertension].
AB  - OBJECTIVE: To elucidate the possible relationship between pregnancy-induced
      hypertension syndrome (PIH) and expression of vimentin, type IV collagen and
      fibronectin in human placenta. METHODS: Nineteen pregnant women (PIH group) and
      15 normal pregnant women (control group) matched for age and gestation were
      recruited. The expression of vimentin, type IV collagen and fibronectin in the
      placenta of PIH patients and normal subjects was investigated using
      immunohistochemical perioxidase-antiperoxidase (PAP) staining technique combined
      with an analysis through a computer-aided microphotographic system and compared
      between the two groups. RESULTS: The average grey value difference (GVD) which
      indicated positive staining of vimentin was 30 +/- 7 in section images of the
      moderate and severe PIH group, significantly lower than that of normal control
      group, 42 +/- 6 and mild PIH group, 42 +/- 9 (P < 0.01). The average GVD of type
      IV collagen in moderate and severe PIH group was 70 +/- 6, significantly higher
      than 29 +/- 4 of control group and 30 +/- 5 of mild PIH group (P < 0.001). The
      average GVD of fibronectin in moderate and severe PIH group was 37 +/- 4,
      significantly higher than that in control group, 31 +/- 4 and mild PIH group, 32
      +/- 6 (P < 0. 05). CONCLUSIONS: There is tight relationship between abnormal
      expression of placental vimentin, type IV collagen, fibronectin and pathogenesis
      of PIH. Furthermore, the severity of PIH is positively correlated with the
      abnormal expression levels of those proteins.

PMID- 15498190
TI  - [Study on cytokeratin and CA125 for diagnosing lymph node micrometastases in
      endometrial cancer].
AB  - OBJECTIVE: To study the roles of cytokeratin (CK) and CA(125) in diagnosing lymph
      node micrometastasis in endometrial cancer. METHODS: The expressions of CK and
      CA(125) in 50 primary tumors and 298 lymph nodes from 50 patients with
      endometrial cancers were analysed by immunohistochemical methods. RESULTS: (1)
      The positive expression rates of CK and CA(125) in primary tumors of cases with
      endometrial cancer were respectively 100%, and 78%. (2) The expressions of CK and
      CA(125) in metastatic lymph nodes were both strong with 100% positive rate. In
      lymph nodes without metastasis, the expressions of CK and CA(125) were both weak,
      with positive rates of 15% and 12% respectively. (3) Among patients with stage I,
      II diseases, tumor recurrence rate was significantly higher in patients with
      positive CK or CA(125) expression in lymph nodes than in patients without CK or
      CA(125) expression (P < 0.05). (4) Multiple regression analysis revealed that in
      stages I, II endometrial cancer, CK expression in lymph nodes, and CA(125)
      expression in lymph nodes together with depth of myometrial invasion were
      relevant factors with tumor recurrence. CONCLUSIONS: CK expression in lymph nodes
      without metastasis can predict lymph node micrometastasis and is an independent
      risk factor for recurrence of disease in stages I, II endometrial cancers.
      CA(125) expression in lymph nodes without metastasis can also suggest lymph node
      micrometastasis, but it is not an independent predictive factor for tumor
      recurrence in stages I, II endometrial cancers.

PMID- 15498191
TI  - [Study on the expression and mutation of cadherin 6 gene in human ovarian
      carcinoma].
AB  - OBJECTIVE: To study expression and mutation of cadherin 6 gene in human ovarian
      tumor tissues and its clinical significance and to explore new molecular
      biomarker of ovarian tumors. METHODS: The expression and mutation of cadherin 6
      in 41 cases of malignant ovarian tumors, 15 cases of benign ovarian tumors and
      borderline ovarian tumors and 17 cases of normal tissues were detected by RT-PCR
      and polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP)
      technique respectively. RESULTS: The positive expression rates of cadherin 6 were
      71% in normal group, 53% in benign ovarian tumors, 24% in malignant ovarian
      tumors, being significantly higher in the former two groups than in malignant
      tumor group (P < 0.05). Statistical analysis revealed a significant correlation
      between cadherin 6 gene expression and clinical stages and histological subtype
      of malignant ovarian tumors. Lower expression rate of cadherin 6 gene was found
      in cancer tissues at stages III approximately IV than at stages I approximately
      II (P < 0.01). No mutation was found in normal group and benign tumor tissues and
      it was observed in 2 out of 41 malignant ovarian tumor tissues. CONCLUSIONS:
      These results suggest that expression of cadherin 6 gene tends to lack in
      advanced ovarian carcinoma with lymph node metastases, as well as in poorly
      differentiated carcinomas. It may be a prognostic marker of ovarian carcinoma.

PMID- 15498192
TI  - [Peripheral blood CD34+-positive mononuclear cells participate in
      neovasculogenesis of human ovarian epithelial carcinoma].
AB  - OBJECTIVE: To observe whether endothelial cell (EC) progenitors (CD(34)(+)
      positive mononuclear cells) participated in neovasculogenesis of ovarian
      epithelial carcinoma through in vitro and in vivo experiments, and to explore the
      mechanism of tumor neovasculogenesis. METHODS: CD(34)(+)-positive mononuclear
      cells were isolated from peripheral blood of ovarian epithelial carcinoma
      patients by means of magnetic beads coated with antibody to CD(34)(+), plated on
      culture dishes coated with human fibronectin in endothelium medium, and examined
      by using RT-PCR, fluorescence-activated cell sorting (FACS) and nitric oxide (NO)
      assay kit for the expression of EC lineage-markers. EC-like cells were labeled
      with DiI ex vivo, and injected into immunodeficiency mice model with transplanted
      hypodermic SKOV3 by caudal vein. After 4 - 6 weeks, the tumor was resected and
      examined by confocal microscopy, and immunohistochemistry. RESULTS: In vitro,
      CD(34)(+)-positive mononuclear cells differentiated into ECs. In animal models of
      SKOV3, EC progenitors (CD(34)(+)-positive mononuclear cells) incorporated into
      sites of neovasculogenesis in tumor, 4 - 6 weeks later DiI-labeled cells
      incorporated into capillaries and small arteries. CONCLUSIONS: The
      neovasculogenesis in human ovarian epithelial carcinoma involves angiogenesis and
      vasculogenesis.

PMID- 15498205
TI  - [Alpha-methylacyl-CoA racemase: a useful marker for diagnosis of prostatic
      carcinoma].

PMID- 15498206
TI  - [Relationship between apoptosis of neurons and microglia activation in
      Alzheimer's disease].
AB  - OBJECTIVE: To assess the relationship between microglia activation and apoptosis
      of neurons, and the significance of activated microglias in the formation and
      progression of senile plaques in Alzheimer's disease. METHODS: IL-1alpha and beta
      amyloid immunohistochemistry, combined with TUNEL assay were used to assess brain
      tissue samples from 10 patients with Alzheimer's disease and 4 negative control
      cases without neurological disease. RESULTS: The number of resting microglias in
      the brains of Alzheimer's disease patients was similar to that of the control
      group (P > 0.05), but the number of activated microglias was significant greater
      in the Alzheimer's disease patients than that of the controls (P < 0.01). The
      activated microglias displayed altered size and morphology, and was therefore,
      categorized into three subtypes as primed, enlarged and phagocytic microglias.
      The numbers of primed, enlarged and phagocytic microglias were 5.4 +/- 0.87, 11.5
      +/- 1.25, and 3.4 +/- 0.32 microglia/mm2 and represented 26.6%, 56.65%, and
      16.75% of all activated microglias respectively. The number of TUNEL positive
      apoptotic neurons was significantly greater in Alzheimer patients than that in
      the control group (P < 0.05). There was a close relationship between the
      apoptosis of neurons and the activation of microglias (P < 0.01). The activated
      microglias were differentially distributed among four different plaque types in
      Alzheimer patients. Many primed (42.3%) and most of the enlarged and phagocytic
      microglias (56.2% and 70.6%) were present in the diffuse neuritic plaques.
      CONCLUSIONS: Hyperplasia and activation of microglias are a common phenomena in
      AD and may play an important role in its pathogenesis. There is a close
      relationship between the apoptosis of neurons and activation of microglias. The
      activation of microglias may play a key pathogenic role in senile plaque
      formation and progression of Alzheimer disease.

PMID- 15498207
TI  - [Pathologic diagnosis of non-Alzheimer type dementia].
AB  - OBJECTIVE: To characterize histopathologic features of non-Alzheimer type
      dementia. METHODS: Bodian, Gallyas-Braak silver staining, tau and ubiquitin
      immunohistochemistry were applied in an analysis of 22 cases of autopsy-proven
      neurodegenerative dementia. Appearance, distribution and immunoreactivity of
      neuronal and glial inclusions in the brain were observed. The final histological
      diagnoses were made according to the pathological criteria for several types of
      common non-Alzheimer type dementia. RESULTS: Among the 22 cases of
      neurodegenerative dementia, 12 cases were identified as non-Alzheimer type
      dementia, including Pick's disease (2 cases), progressive supranuclear palsy (3
      cases) and corticobasal degeneration (3 cases), dementia with Lewy bodies (1
      case), and Parkinson's disease (3 cases). Another 10 cases consisted of pure
      Alzheimer's disease (AD, 9 cases) and AD combined with argyrophilic grain disease
      (1 case). Characteristic neuronal and glial inclusions, such as classical and
      cortical Lewy body, Pick body, Globous NFTs, astrocytic plaque and tufted
      astrocyte, argyrophilic grain were found in the brains of non-Alzheimer type
      dementia. Classical and cortical Lewy bodies were not argyrophilic but were
      immunoreactive to ubiquitin. Pick bodies, Globous NFTs, astrocytic plaques,
      tufted astrocytes and argyrophilic grains were all argyrophilic. Pick bodies
      showed tau and ubiquitin immunoreactivity. However, Globous NFTs, astrocytic
      plaques, tufted astrocytes, and argyrophilic grains were reactive only to tau
      immunohistochemistry. CONCLUSIONS: Findings of characteristic neuronal and glial
      inclusions may help to differentiate non-Alzheimer type dementia from AD, and in
      conjunction with Gallyas-Braak staining and immunohistochemistry for tau and
      ubiquitin, to further define histopathologic subcategories of non-Alzheimer type
      dementia.

PMID- 15498208
TI  - [Genome-wide genetic study of medulloblastoma using allelotype analysis].
AB  - OBJECTIVE: To investigate global genetic alterations in medulloblastoma, and to
      localize critical chromosomal loci with allelic imbalances associated with the
      development of medulloblastoma. METHODS: A high-resolution genome-wide allelotype
      analysis, including 384 microsatellite markers, was performed in 12
      medulloblastomas. RESULTS: An average of 238 (62.3%) allelic imbalances were
      detected on all 39 autosomal arms. Non-random allelic gains or losses were
      detected on chromosomes 7q (58.3%), 8p (66.7%), 16q (58.3%), 17p (58.3%) and 17q
      (66.7%). In addition, chromosomal arms with frequencies of allelic imbalances
      higher than the mean percentage were identified on 3p (33.3%), 3q (33.3%), 4q
      (41.7%), 7p (33.3%), 8q (41.7%), 10q (41.7%), 13q (33.3%), 14q (33.3%) and 20q
      (33.3%). No relationship was found between the frequency of allelic imbalances
      and the clinical outcome of the patients. CONCLUSIONS: A global view of the
      genetic alterations in medulloblastoma was provided. The allelic imbalances
      involving chromosomes 7q, 8p, 16q, 17p and 17q may play an important role in the
      pathogenesis of medulloblastoma.

PMID- 15498209
TI  - [Traumatic cerebral infarction: a histopathological study of 17 cases].
AB  - OBJECTIVE: To assess the morphologic changes in traumatic cerebral infarction and
      to discuss its mechanism. METHODS: Specimens from seventeen cases of cerebral
      infarction were selected from 81 patients with severe brain injury, and subject
      to routine gross and histological examinations. RESULTS: (1) The cerebral
      infarction in all cases was hemorrhagic in nature with a wedged or irregular
      shape upon gross inspection. The lesions were found in occipital gyrus (8 cases),
      occipital lobes (3 cases), basal nuclei (3 cases), cingulate gyrus (2 cases), and
      lateral occipitotemporal gyrus (1 case). Histologically, the lesions were located
      at the junction between the cortex and medulla, showing congestion, edema,
      hemorrhage, necrotic nerve tissue and blood vessels. In severe cases, the lesion
      extended into the entire cortex and subarachnoid spaces. (2) Swelling of the
      brain and cerebral hernia were found in all cases, 8 of which demonstrated that
      the posterior cerebral artery was compressed and stenotic within the space
      between the crus cerebri and uncus. CONCLUSION: Brain tissue necrosis in
      traumatic cerebral infarction is the result of brain swelling and cerebral hernia
      formation, following congestion, bleeding and ischemia due to vasculature
      compression.

PMID- 15498210
TI  - [Assessment of P504S immunohistochemistry in diagnosis and differential diagnosis
      of prostatic adenocarcinoma].
AB  - OBJECTIVE: To assess the utility of P504S immunohistochemistry in the diagnosis
      and differential diagnosis of prostatic adenocarcinoma. METHODS: Light microscopy
      and immunohistochemistry examinations (EnVision staining) were performed in 117
      cases of prostatic adenocarcinoma, PIN, AAH, ASAP, BPH and normal prostatic
      tissue to correlate the morphology and protein expression of P504S, 34betaE12,
      and P63. RESULTS: Seventy-one of the 78 (91%) cases of prostatic adenocarcinoma
      stained positive for P504S, with strong cytoplasmic granular staining in most
      cases, and a weak or intense granular staining along the circumferential luminal
      and apical cell border membrane in a few cases. Negative P504S immunostaining was
      observed in 7 of 78 (9%) cases of prostatic adenocarcinoma, all of which were
      clear cell type prostatic adenocarcinoma. Cases of PIN (9 cases), AAH (6 cases)
      and ASAP (2 cases) showed various expression levels of P504S. Sixty-five of 68
      (96%) cases of normal prostates and BPH were negative for P504S and basal cell
      hyperplasia cases were also negative. CONCLUSIONS: P504S is a useful marker for
      microscopic diagnosis of prostatic adenocarcinoma, and immunohistochemistry study
      using a combination of P504S and 34betaE12/p63 may be of greater benefit in
      aiding the differential diagnoses.

PMID- 15498211
TI  - [Pathological diagnosis and ultrastructure features of primary pulmonary
      cryptococcosis: a study of 27 cases].
AB  - OBJECTIVE: To investigate diagnostic histopathology and ultrastructure features
      of primary pulmonary cryptococcosis (PC). METHODS: Clinical data and pathologic
      findings of 27 cases of PC were retrospectively reviewed, light and electron
      microscopic evaluations and histochemistry stain studies were performed. RESULTS:
      The specimens consisted of 2 fine-needle aspiration lung biopsies and 25 cases of
      open lung biopsies. Cryptococcosis granuloma formation was identifiable by
      histopathological examination in 25 of 27 cases, with gum-like lesion and fungi
      in the remaining 2 cases. The detection rates of cryptococcus neoformans (CN) by
      mucicarmine (MC), periodic acid-Schiff (PAS), alcian blue (AB) and Grocott
      methenamine-silver (GMS) were 87.0% (20/23), 100% (27/27), 66.7% (18/27), and
      100% (23/23) respectively. Under the electron microscope, most CN had a simple
      structure with a few organelles. The capsule was seen in all organisms. A
      percentage of the organisms showed nuclei, nucleoli, mitochondria and vacuoles.
      The detection rate of CN by EM was 91.7% (11/12). CONCLUSIONS: The clinical
      manifestation and imaging of PC are nonspecific for PC. Lung biopsy is the major
      diagnostic modality. The detection rate by electron microscopy was quite high.
      Therefore, a correct diagnosis of pulmonary cyrptococcosis should rely on the
      combination of histopathological evaluation, histochemistry staining and/or
      electron microscopic examination.

PMID- 15498212
TI  - [Relationship between microsatellite alterations on chromosome 8 and
      clinicopathological characteristics in hepatocellular carcinoma].
AB  - OBJECTIVE: To study the features of microsatellite alterations and their
      association with clinicopathological characteristics of hepatocellular carcinoma
      (HCC). METHODS: Ten high-polymorphic microsatellite markers on chromosome 8 were
      selected to detect the loss of heterozygosity (LOH), microsatellite instability
      (MSI) and allelic imbalance (AI) in 56 HCCs using automatic capillary array
      electrophoresis DNA analysis system. RESULTS: LOH was found in 37 of 56 HCCs
      (66.1%) on at least 10 locus. The three most frequently altered loci were D8S261
      (53.5%, 23/43), D8S1721 (52.5%, 21/40) and D8S1771 (52.5%, 21/40). LOH on D8S277
      was significantly higher in cases with positive serum HBsAg than in those with
      negative HBsAg (P < 0.01). Similarly, LOH on D8S261, D8S298 and D8S1733 occurred
      more frequently in patients with negative HBsAg than those with positive HBsAg (P
      < 0.01). LOH on D8S298 and D8S1771 were more frequent in tumors larger than 3 cm
      in size (P < 0.05 and P < 0.01 respectively). LOH frequencies of D8S1721 were
      significantly higher in cases with absent or partially encapsulated tumor than in
      those with intact tumor capsule (P < 0.05). LOH on D8S298 and D8S1771 were more
      frequently detected in tumors with intrahepatic metastasis than those without (P
      < 0.01). MSI was found in 12.5% (7/56) cases. AI was found in 19.6% (11/56) of
      all cases examined. CONCLUSIONS: Microsatellite alterations on chromosome 8 were
      frequent in HCC. LOH, possibly representing alterations of the tumor suppressor
      pathway, may play an important role in hepatocarcinogenesis. MSI, reflecting a
      dysfunction of the mismatch repair pathway, may also contribute to this process,
      but in a less significant way. LOH at some particular loci is associated with
      certain clinicopathological parameters of human HCC.

PMID- 15498213
TI  - [Methylation of mismatch repair gene (MMR) in primary hepatocellular carcinoma].
AB  - OBJECTIVE: To assess the role of methylated mismatch repair (MMR) genes (hMLH1,
      hMSH2 and hMSH3) in the carcinogenesis and progression of hepatocellular
      carcinoma (HCC). METHODS: Samples of 38 cases of HCC along with their
      corresponding noncancerous tissues, 2 samples of donated normal tissue and 6 cell
      lines were collected and subject to the methylation-specific PCR (MSP) to examine
      promoter methylation status of MLH1, MSH2 and MSH3. Six tumor cell lines were
      analyzed before and after 5-aza-2'-deoxycytidine treatment. In addition,
      alterations of mRNA expression of MMRs were investigated by quantitative reverse
      transcription-PCR. RESULTS: CpG island methylation of hMLH1 and hMSH2 was
      observed in 13.2% (5 of 38 samples) and 68.4% (26 of 38 samples) respectively in
      HCC, 2.6% (1 of 38 samples) and 55.3% (21 of 38) respectively in corresponding
      noncancerous tissues, but not in normal control tissues. Promoter methylation of
      the hMSH2 gene was present in 83.3% of cell lines tested (5/6), but none were
      observed for the hMLH1 gene. Promoter methylation of the hMSH3 gene was not
      identified in any tissue samples or cell lines. After 5-aza-2'-deoxycytidine
      treatment, hMSH2 methylation was induced or completely reversed, and its mRNA
      expression was increased in most cell lines. CONCLUSIONS: Our results suggest
      that promoter hypermethylation of hMLH1 and hMSH2 genes is common in HCC.
      Particularly, there is a high frequency of methylation of hMSH2 in both cancer
      and noncancerous tissues, but not in normal control tissue. Therefore,
      hypermethylation of MMR genes, especially hMSH2, may be involved in the
      carcinogenesis of HCC and may serve as an early diagnostic marker for HCC. The
      close correlation between hMSH2 methylation and low expression of its mRNA
      suggests that hMSH2 methylation is an important pathway in the regulation of gene
      expression.

PMID- 15498214
TI  - [Morphologic variants and immunohistochemical features of hepatic
      angiomyolipoma].
AB  - OBJECTIVE: To study the clinicopathological characteristics, immunohistochemical
      features and differential diagnosis of hepatic angiomyolipoma (AML). METHODS: The
      clinicopathological features of hepatic AML were systematically examined in 44
      surgically resected tumor specimens, with additional immunohistochemistry study
      using 10 relevant antibodies. RESULTS: The tumors were composed of various
      amounts of three components, i.e. blood vessels, smooth muscle cells and adipose
      cells. According to the proportions of each of these tissue components, AML was
      subcategorized into the classical type (n = 13), myomatous type (n = 25),
      lipomatous type (n = 4), and angiomatous type (n = 2). Myoid cells displayed
      various morphology, including epithelioid, intermediate (ovoid or short spindle),
      spindle, oncocytic, and pleomorphic features. Hematopoietic elements were present
      as minor findings in eight tumors. Immunohistochemically, the tumor cells were
      strongly positive for HMB45 (44/44, 100%), SMA (38/38, 100%) and CD117 (30/38,
      78.9%). CONCLUSIONS: A correct diagnosis of hepatic AML might be difficult due to
      its various growth patterns and cell types. HMB-45 positivity in the myoid cells
      is a key feature for hepatic AML. CD117 may be another useful ancillary marker
      for reaching a definite diagnosis.

PMID- 15498215
TI  - [Clinicopathological study of intermediate trophoblastic non-tumor lesions:
      exaggerated placental site and placental site nodule].
AB  - OBJECTIVE: To investigate the clinicopathological features of intermediate
      trophoblastic non-tumor lesions, and to evaluate the position of
      immunohistochemistry in differential diagnoses. METHODS: Clinical presentation
      and morphological study of 15 cases of exaggerated placental site (EPS) and 4
      cases of placental site nodule or plaque (PSNP) were reviewed.
      Immunohistochemical stains for hCG, hPL, inhibin-alpha, PLAP, CK18 and Ki-67 were
      performed. RESULTS: The age of patients ranged from 25 to 40 years with an
      average of 31.5 years for EPS and 26 to 39 years with an average of 34.3 years
      for PSNP. Microscopically, EPS was characterized by cords and small sheets of
      implantation site intermediate trophoblasts infiltrating the endometrium,
      myometrium and arterial walls. The general histological structures of the
      endometrium and myometrium were preserved. PSNP was characterized by multiple
      circumscribed nodular lesions consisting of so-called chorionic-type intermediate
      trophoblasts and hyaline-like matrix present in the endometrium.
      Immunohistochemical stainings for hPL and CK18 were positive in the 15 EPS cases.
      Immunoreactivity for CK18, Inhibin-alpha and PLAP was detected in 4 PSNP cases.
      The Ki-67 labeling index in 15 EPS cases was low (< or = 5%), while Ki-67 index
      in 4 PSNP cases was close to 0. CONCLUSIONS: The clinical presentation and
      pathological features of EPS and PSNP differ from those of trophoblastic tumors
      (placental site trophoblastic tumor, epithelioid trophoblastic tumor and
      choriocarcinoma). Immunochemical staining is of great value in their differential
      diagnoses.

PMID- 15498216
TI  - [Clinicopathological analysis of primary intestinal non-Hodgkin's lymphoma: a
      report of 32 cases].
AB  - OBJECTIVE: To investigate the clinical and pathological features and prognostic
      factors of primary intestinal non-Hodgkin's lymphoma (NHL). METHODS: Thirty-Two
      cases of intestinal NHL were studied clinically and pathologically. All cases
      were reclassified according to the WHO classification of lymphoma in 2001.
      RESULTS: Twenty-one cases (65.6%) were diagnosed as B-cell lymphomas, including
      15 cases of diffuse large B-cell lymphoma, 2 cases of mantle cell lymphoma, 1
      case of follicular lymphoma, 2 cases of MALT lymphoma and 1 case of Burkitt's
      lymphoma. Ten cases (31.2%) were diagnosed as T cell lymphomas, including 2
      enteropathy-associated T cell lymphomas (EATCL) and 8 cases non-EATCL. One case
      (3.1%) was diagnosed as histiocytic lymphoma. Nine cases were at stage I-II and
      23 cases were at stage III-IV. Follow-up information was available in all cases
      ranging from 4 to 168 months (mean 25.6 months). Fifteen cases died of the
      disease. The mortality rates were 33% for B cell lymphoma and 80% for T cell
      neoplasms. Based on Cox multivariate analysis, the clinical stage and
      histological types of the disease were important prognostic factors (P < 0.05). T
      cell lymphoma had a relatively poor prognosis. CONCLUSIONS: Diffuse large B cell
      lymphoma is the most common subtype of primary intestinal lymphomas. Colon is the
      most common site involved, followed by the small intestine. Early stage of the
      disease and low-grade lymphoma appear to have a better prognosis. T cell lymphoma
      has a very poor prognosis.

PMID- 15498217
TI  - [Effects of ectopic glial fibrillary acidic protein/green fluorescent protein
      gene expression on cellular differentiation and proliferation of human glioma
      cell line].
AB  - OBJECTIVE: To investigate the biological effects of ectopic overexpression of
      glial fibrillary acidic protein (GFAP) in human malignant glioma cell line, and
      to explore new method of differentiation induction gene therapy for gliomas.
      METHODS: A eukaryotic expression vector containing 1.1 kb GFAP cDNA fused with
      green fluorescent protein (GFP) gene, pIRGFP-GFAP, was transfected into human SHG
      44 glioma cell line by lipofectamine. The expression of GFAP/GFP gene and their
      proteins were detected by fluorescent real-time monitoring, in situ
      hybridization, Western blot and immunocytochemistry. Flow cytometry, soft agar
      colony formation and other methods were used to measure the effects of exogenous
      GFAP expression on cell cycle progression, morphology and growth features of the
      transfected glioma cells. RESULTS: The expressions of GFAP mRNA and its protein
      were markedly increased in SHG-44 cells upon stable transfection with pIRGFP/GFAP
      vector. Profound morphological changes in these cells were also observed,
      including the formation of abundant, stellate and thin cytoplasmic processes and
      a reduction of atypia. Cell proliferation rate and its tumorigenecity on soft
      agar were markedly reduced. In addition, cell cycle analysis revealed a
      percentage decrease of cell populations at G0/G1 and G2/M phases. CONCLUSIONS:
      Ectopic overexpression of GFAP gene could significantly suppress the growth of
      SHG-44 malignant glioma cells along with an induction of differentiation. These
      results imply that forced over-expression of GFAP gene may provide a new strategy
      for glioma therapy.

PMID- 15498218
TI  - [Antisense hTERT inhibits gene expression and functional activity of telomerase
      in leukemia cell lines].
AB  - OBJECTIVE: To explore the inhibitory effects of gene expression and functional
      activity of telomerase in leukemia cell lines by in vitro antisense hTERT
      treatment. METHODS: An antisense hTERT eukaryotic expression vector was
      constructed by using gene recombination technique, targeting the 5' end mRNA
      sequence of the telomerase catalytic subunit. The vector expression in leukemia
      cell lines (HL60 and K562) was achieved by transfection using the SuperFect
      transfection reagent (Qiagen). After transfection, ectopic expression of the
      telomerase catalytic subunit was analyzed by quantitative fluorescence real-time
      RT-PCR, and cellular apoptosis and cell cycle parameters were evaluated by flow
      cytometry respectively. RESULTS: An antisense pcDNA-hTERT eukaryotic expression
      vector was successfully constructed. Leukemia cell lines transfected with
      antisense hTERT constructed displayed a significant inhibition of gene expression
      of telomerase and its activity in vitro, as compared with the result of the
      control groups (without transfection and vector control). CONCLUSION: In-vitro
      antisense hTERT expression may down-regulate the gene expression and biological
      activity of telomerase in leukemia cells, suggesting a possibility of gene
      therapy against human malignancy through the telomerase-targeted molecular
      mechanism.

PMID- 15498219
TI  - [mtDNA mutations in mouse tumors].
AB  - OBJECTIVE: To investigate variations of mtDNA in mouse tumors and to explore the
      relationship between mtDNA mutations and murine carcinogenesis. METHODS:
      Variations of D-loop, ND3 and tRNAIle + Glu + Met gene fragments of mtDNA from
      six mouse tumor cell lines were analyzed by PCR-RFLP and PCR-SSCP techniques.
      RESULTS: ND3 and tRNAIle + Glu + Met gene fragments of mtDNA from the tumors
      showed no variations at 27 endonuclease sites. The D-loop of mtDNA from Hca-F
      demonstrated an additional endonuclease site of Hinf I in contrast to the inbred
      mouse. Upon PCR-SSCP analysis, the D-loop of mtDNA was found to possess mutations
      in 4 of 6 tumors. CONCLUSION: D-loop appears to be the hot spot for tumor mtDNA
      mutations, which may contribute to the carcinogenesis of murine tumors.

PMID- 15498225
TI  - [The molecular genetics of oligodendroglioma].

PMID- 15498226
TI  - [Modern immunocytochemistry and fluorescence-imaging technology].

PMID- 15498236
TI  - [Current situation and challenges to China's fight against acquired
      immunodeficiency syndrome].

PMID- 15498227
TI  - [Cat scrach disease].

PMID- 15498237
TI  - [Active prevention and treatment of superinfection with HBV, HCV and HIV].

PMID- 15498238
TI  - [Community-based survey on human immunodeficiency virus infection among injection
      drug users in Sichuan, China].
AB  - OBJECTIVE: To investigate prevalence of human immunodeficiency virus (HIV)
      infection and risk factors for its transmission among injection drug users (IDUs)
      in Liangshan Yizu Autonomous Prefecture of Sichuan Province, China. METHODS: A
      community-based survey was conducted to investigate demographic characteristics,
      pattern and frequency of sharing injection equipment, and sexual behaviors in
      IDUs. Blood samples were also collected from them to detect for antibodies
      against HIV and syphilis. RESULTS: A total of 379 subjects were recruited with
      informed consent for study through community outreach and peer recruiting
      methods. Their prevalence of HIV infection was 11.3% (43/379). Ethnicity,
      frequency of sharing syringes and cotton swab during the past three months and
      syphilis infection associated with HIV infection by univariate analysis using chi
      square test. Multivariate logistic regression analysis showed odds ratio of
      frequency of sharing syringes for HIV infection during the past three months was
      2.28 (95% CI 1.18 - 4.43), and that for syphilis infection 3.10 (95% CI 1.48 -
      6.48). CONCLUSION: Frequency of sharing syringes during the past three months
      associated with syphilis and HIV infection.

PMID- 15498239
TI  - [Effect of selenomethionine on cell division of esophageal cancer line].

PMID- 15498240
TI  - [Distribution of recombinant human immunodeficiency virus type-1 CRF01_AE strains
      in China and its sequence variations in the env V3-C3 region].
AB  - OBJECTIVE: To characterize CRF01_AE strains of recombinant human immunodeficiency
      virus type-1 (HIV-1) found in the Second National Molecular Epidemiology Study on
      HIV in China and to analyze its sequence variation in the env V3-C3 region during
      the First National Molecular Epidemiology Study (NMES1, 1996 - 1998) to the
      Second National Molecular Epidemiology Study (NMES2, 2001 - 2002). METHODS: DNA
      was extracted from peripheal blood mononuclear cells of the subjects with HIV
      infection. The env C2-V4 region of HIV-1 was amplified with nested polymerase
      chain reaction (n-PCR). PCR products were directly sequenced using ABI 377 DNA
      sequencer, then the gene-based phylogenetic tree was constructed and its
      variation of amino acids was analyzed with GCG software. RESULTS: Totally, 169
      strains of recombinant HIV-1 CRF01_AE were identified from blood samples
      collected from different high risk groups in 17 of 31 provinces, municipalities
      and autonomous regions all over China by the end of 2002. Although sexual
      transmission still dominated during NMES1 (62.2%, 23/37) and NMES2 (55.3%,
      73/132), prevalence of HIV-1 CRF01_AE in intravenous drug users (IDUs) increased
      to 41.6% (57/137) during NMES2 from 27% (10/37) during NMES1. Phylogenetic tree
      analysis showed that HIV-1 CRF01_AE strains prevalent in IDUs during NMES2 did
      not cluster with those prevalent in the subjects infected by sexual transmission
      during NMES2 and those in IDUs during NMES1. The amino acid residues of V3 region
      of HIV-1 CRF01_AE in IDUs were relatively conservative, but the sixth, eighth,
      ninth, tenth, twelfth, fifteenth, sixteenth amino acid residues of C3 region
      displayed regular changes. CONCLUSIONS: HIV-1 CRF01_AE strain has been introduced
      into inland provinces from southeastern coast areas and southwestern border
      areas, with an increasing prevalence in IDUs. The sequence of env V3-C3 region of
      recombinant HIV-1 CRF01_AE strains prevalent in IDUs during NMES2 was obviously
      different from that during NMES1, suggesting that HIV-1 CRF01_AE strains
      prevalent in IDUs during NMES2 might come from a new source and have a potential
      to spread.

PMID- 15498241
TI  - [Evaluation of a pilot study on needle and syringe exchange program among
      injecting drug users in a community in Guangdong, China].
AB  - OBJECTIVE: To evaluate the feasibility and effectiveness of needle and syringe
      exchange program among a community of injecting drug users (IDUs) on AIDS
      prevention. METHODS: A quasi-experiment design was used in a controlled community
      intervention study. Needle and syringe exchange program was implemented for 10
      months in IDUs of an intervention community, including peer education and health
      education, provision of free needles and syringes, and collecting back of used
      needles and syringes by trained peer educators and local health workers, whereas
      no intervention measure in a control community was instituted. Interviews with
      IDUs were conducted before and after intervention with a snowballing strategy to
      evaluate its effectiveness. RESULTS: A total of 428 and 429 IDUs were interviewed
      with structured questionnaire before and after intervention in intervention and
      control communities, respectively. Results revealed that awareness of HIV-related
      knowledge increased from 29.4% to 58.7% in the intervention community.
      Multivariate logistic regression analysis showed that awareness of HIV-related
      knowledge was higher in those who had read health education materials (OR = 2.93,
      95% CI 2.12 - 4.04). As compared with the baseline data, frequency of sharing
      needles and syringes in past 30 days in the intervention community decreased from
      48.9% to 20.4% in before intervention community (chi(2) = 41.02, P = 0.001),
      whereas there was no significant change in the control community. The causes of
      sharing needles and syringes in the intervention community included 'disable to
      get needle and syringe during the night', 'lack of needle and syringe when
      injecting at friend's home', 'not daring to buy needle and syringe for fear of
      being arrested' and 'no money to buy needle and syringe', declined markedly.
      CONCLUSIONS: Needle and syringe exchange program was feasible and effective in
      reducing their risky drug injecting behavior among IDUs in communities. Such
      strategy should be adopted in the country to reduce rapid spread of HIV.

PMID- 15498242
TI  - [Analysis for epidemic trend of acquired immunodeficiency syndrome in Yunnan
      Province of China].
AB  - OBJECTIVE: To understand epidemiologic characteristics and changes in epidemic
      trend of human immunodeficiency virus infection and acquired immunodeficiency
      syndrome (HIV/AIDS) in different areas and populations of Yunnan Province.
      METHODS: Seroepidemiological studies were conducted in injection drug users
      (IDUs), women sex workers, whoring goers, patients with sexually transmitted
      disease (STD), patients with tuberculosis, pregnant women and blood donors with
      sentinel surveillance, ad hoc investigations, regular case-finding and data
      collection during 1989 to 2003 in Yunnan Province. RESULTS: Relatively high
      prevalence of HIV/AIDS was firstly found in IDUs from border areas of the
      province in 1989. By December of 2003, totally 14 905 cases with HIV infection
      were reported in 121 counties of 16 prefectures in Yunnan Province. Prevalence of
      HIV infection ranged from 21.2% to 27.8% in IDUs, over 40% in IDUs from six
      areas, and 1.23% to 6.67% and 0.3% to 1.8% in underground prostitutes and whoring
      goers, respectively. Prevalence of HIV infection was 2.1% to 2.7%, 10.8% in
      specific areas, in male patients with STD, and was 0.14% to 0.25% in pregnant
      women during 1993 to 2002 and increased to 0.37% in 2003. Prevalence of HIV
      infection ranged 1.5% to 1.6% in patients with tuberculosis and 0.01% in blood
      donors during 1999 to 2000 and increased to 0.07% in 2003. CONCLUSIONS: Epidemic
      of HIV infection began in late 1980s in Yunnan, then spread from border areas to
      inland through IDUs, maintaining a higher prevalence in them to date. Sexual
      transmission of HIV/AIDS showed an increasing trend in them, with a low
      prevalence in general population, but appeared a wide spread in local areas.

PMID- 15498243
TI  - [Investigation on emerging rate and prevalence of male homosexuality in Hangzhou
      City].
AB  - OBJECTIVE: To understand prevalence of male homosexuality in Hangzhou, Zhejiang
      Provicne of China. METHODS: To investigate emerging rate of male homosexuality
      and infer its prevalence in public gathering by observation at fixed points and
      questionnaire survey in gay men. RESULTS: There were 2 012.5 male homosexuals
      taking part in public gatherings, with 95% confidence interval of 1 899 - 2 129,
      in Hangzhou. Frequency of such activities they took part in was once every 3 - 15
      days (11.3 +/- 2.7) days. Each gay man knew 1.51 +/- 0.33 (0 - 6) other male
      homosexuals who never exposed their sexual orientation. The emerging number of
      male homosexuals was 5 051.38. CONCLUSION: The emerging rate of male
      homosexuality was 0.58%, with its prevalence of about 1% - 2% in public
      gatherings in Hangzhou.

PMID- 15498244
TI  - [A study on awareness of sexually-transmitted disease/acquired immunodeficiency
      syndrome and related factors among migrant workers in Hangzhou City, Zhejiang
      Province of China].
AB  - OBJECTIVE: To understand awareness on transmission routes of sexually transmitted
      diseases and acquired immunodeficiency syndrome (STD/AIDS) among migrant workers
      in Hangzhou City, Zhejiang Province. METHODS: A cross-sectional study was
      conducted in migrant workers in Hangzhou with self-administered anonymous
      questionnaire to collect their demographic information and awareness on STD/AIDS.
      All the data were analyzed by SPSS 11.0 software. RESULTS: A total of 3 001
      subjects were interviewed. Most of them have already had some knowledge about
      STD/AIDS, but not complete. There were 556 (18.8%) migrant workers did not
      understand that condom could prevent from STD, and 759 did not know if it could
      do. There were 357 (11.9%) workers did not know AIDS could be prevented, and 746
      (24.9%) thought that AIDS could be cured. There were 637 workers did not know
      that correct use of condom could reduce occurrence of AIDS, and 725 of them
      thought AIDS could be infected by hands-shaking and hugging with patients of
      AIDS. There existed statistically significant difference in awareness on STD/AIDS
      between men and women, workers with varied marital status and education levels.
      CONCLUSIONS: Awareness on STD/AIDS in migrant workers was smattering, allowing of
      not optimistic. Community-based health education on knowledge about STD/AIDS
      should be strengthened among high-risk migrant workers with varied channels to
      improve their awareness.

PMID- 15498246
TI  - [Effects of iron supplementation on human serum level of transferrin receptor].
AB  - OBJECTIVE: To study trend of dynamic change in level of serum transferrin
      receptor (sTfR) in the process of iron supplementation to provide evidence for
      sTfR in evaluating the efficacy of iron supplementation. METHODS: Totally, 942
      child-bearing-age women aged 18 to 45 years were selected from Longfang City,
      Hebei Province and Shunyi County, Beijing. Biochemical indicators of iron
      metabolism were measured for all of them, including serum levels of ferritin (SF)
      and zinc protoporphyrin (ZPP), and hemoglobin (Hb). According to the current
      criteria for assessing iron status, women were screened for iron deficiency
      erythropoiesis (IDE) or iron deficiency anemia (IDA). Seventy-two women agreed to
      participate in the study, and 59 of them finished whole dynamic observations with
      signed informed consent. Four capsules of ferrous L-threonate (containing 7 mg of
      iron element per capsule) were administered for women with IDE every other day
      and for women with IDA every day, respectively, for 12 weeks. Serum biochemical
      indicators and level of sTfR were measured in 0 wk, 3 wk, 6 wk, 9 wk and 12 wk,
      respectively, during the process of iron supplementation, and their dynamic
      changes were observed. RESULTS: Level of sTfR in women with IDE and IDA was
      (26.62 +/- 10.57) nmol/L and (41.25 +/- 21.96) nmol/L, respectively,
      significantly higher than normal level. During the process of iron
      supplementation, level of sTfR changed as the following characteristics. In women
      with IDE, level of sTfR kept stable within the first 3 weeks of iron
      supplementation, then dropped gradually and progressively, reached to normal,
      with (17.86 +/- 5.57) nmol/L, in the 12 wk after iron supplementation. In women
      with IDA, level of sTfR dropped quickly within the first 3 wk of iron
      supplementation, then dropped slowly until the 9th wk and kept stable, and
      reached to normal level in the 12 wk, with (19.54 +/- 5.94) nmol/L and a ratio of
      sTfR/SF of 12.23 +/- 4.34. Ratio of sTfR/SF changed as level of sTfR during the
      process of iron supplementation. Level of sTfR correlated reversely with levels
      of Hb and SF and positively with level of ZPP. CONCLUSION: Serum level of sTfR in
      child-bearing age women gradually decreased to normal with the restoration of
      their normal iron status during the process of iron supplementation and could be
      used as a specific indicator for assessing efficacy of iron supplementation.

PMID- 15498245
TI  - [Association between the functional monoamine oxidase A gene polymorphism and
      aggressively driving behavior].
AB  - OBJECTIVE: This study is purposed to explore the relationship between
      aggressively driving behavior and functional polymorphism in the promoter region
      of the monoamine oxidase-A (MAOA) gene. METHODS: A total of 348 automobile
      drivers were investigated with Deffenbacher's driver anger scale, driving
      vengeance questionnaire (DVQ) and driver aggression behavior questionnaire.
      Eighty-eight drivers were selected as more, medium and less aggressive group,
      each. Polymerase chain reaction (PCR) and 2.5% agarose gel electrophoresisi were
      adopted to detect the polymorphism of functional 30 bp-uVNTR in the promoter
      region of the X-chromosomal MAOA gene and their frequencies of varied genotypes
      were estimated. RESULTS: Two alleles with 3 and 4 repeats of 30 bp-uVNTR were
      detected in the drivers. Among the more aggressive group, number of the allele
      with 3 repeats of 30 bp-uVNTR (63/88) was significantly more than that with 4
      repeats (25/88) (chi(2) = 10.21, P < 0.01), and number of the allele with 4
      repeats of 30 bp-uVNTR was more in the less aggressive group, indicating that
      persons with allele of 3 repeats of 30 bp VNTR were more aggressive in their
      driving than those with 4 repeats. CONCLUSIONS: Aggressively driving behavior in
      drivers possibly related to their functional MAOA-uVNTR polymorphism. Effect of
      the gene on aggressively driving behavior should be further studied.

PMID- 15498247
TI  - [Diagnosis error in latent acute thallium poisoning--a case report].

PMID- 15498248
TI  - [An epidemiological study on omphalocele in China during 1996 to 2000].
AB  - OBJECTIVE: To understand the trend of incidence of omphalocele and its
      epidemiological characteristics in China during 1996 to 2000. METHODS:
      Surveillance data of omphalocele were collected from 460 hospitals at county
      level or above county level, involving all births with 28-week gestation to 7
      days after delivery, including live births, fetal deaths and stillbirths in 31
      provinces, autonomous regions and municipalities all over the country during 1996
      to 2000. RESULTS: Overall incidence of omphalocele in China was 1.52 per 10 000
      live births, with an increasing trend during 1996 to 2000. Incidence of
      omphalocele was 1.40 per 10 000 and 1.83 per 10 000 in the rural and urban areas,
      respectively, with a statistically significant difference (P < 0.05), and 1.54
      per 10 000 and 1.41 per 10 000 in boys and girls, respectively. Babies of
      omphalocele associated with other malformation accounted for 30.77% of the total
      cases. Perinatal fatality rate of omphalocele was 51.18%, with prenatal
      diagnostic rate of 31.07%. CONCLUSIONS: Prevalence of omphalocele appeared an
      increasing trend in China during the period from 1996 to 2000. Occurrence of
      omphalocele was more frequent in rural areas than that in urban areas. Perinatal
      fatality rate in babies with omphalocele was higher and fatality of associated
      omphalocele was higher than that of simple one. It is suggested that management
      of perinatal care and level of prenatal diagnosis for omphalocele should be
      improved.

PMID- 15498249
TI  - [Effects of shen mai injection on blood superoxide dismutase in silicosis].

PMID- 15498250
TI  - [Combination of direct-ELISA and PCR for the rapid detection and identification
      of Salmonella spp].
AB  - OBJECTIVE: To develop a protocol for the rapid detection of Salmonellae. METHODS:
      A mono-antibody-based direct-ELISA and PCR methods for the detection of
      Salmonella were developed previously. This study assessed the accuracy of both
      direct-ELISA and PCR methods for the rapid detection of Salmonella and set up a
      new detection protocol. RESULTS: The sensitivity of the PCR method was higher
      than that of direct-ELISA method. In the 2002 spring physical examination for
      employees, 1 546 human fecal samples were examined by the combination of direct
      ELISA and PCR method. Compared with the results of national standard method, the
      sensitivity and specificity of direct ELISA was 100% and 97.14%, respectively,
      while those of PCR method reached both 100%. It also indicated that combination
      use of two methods could give positive report within 40 hrs, and also achieve
      high sensitivity and specificity. CONCLUSIONS: Based on the results obtained, a
      protocol for the rapid detection of Salmonella was developed. The first step is
      to us direct-ELISA method to screen the large number of samples, and then use PCR
      method to validate the ELISA positive samples, and the final step is, if needed,
      is to use the national standard method to determine the serotypes of Salmonellae.

PMID- 15498251
TI  - [Influence of alcohol on insulin sensitivity and insulin receptor substrate-1
      mRNA expression in rat skeletal muscle].
AB  - OBJECTIVE: To investigate the molecular mechanism of the effect of alcohol on
      insulin sensitivity. METHODS: Four groups of Wistar rats were used, i.e. control
      (C) group, and low (L), moderate (M) and high (H) alcohol group. Alcohol doses of
      each group were 0, 0.6, 1.8 and 3.0 ml.(kg.bw)(-1).day(-1). Each group was
      comprised of 10 male and 10 female rats. Alcohol was given to rats by gastric
      intubation. Thirteen weeks later, serum was collected for testing of fasting
      plasma glucose and insulin. HOMA-IR index of each group were calculated. Total
      muscle RNA was extracted using Trizol Reagent (Promega). The expression level of
      IRS-1 mRNA in muscle was detected by RT-PCR. RESULTS: In female rats, the fasting
      plasma glucose of group (8.36 +/- 0.57) mmol/L was higher and the fasting plasma
      insulin (15.25 +/- 3.32) was lower than those of group C (7.56 +/- 0.85, 20.80 +/
      3.25). The HOMA-IR of group L (1.775 3 +/- 0.138 1) was lower than that of group
      C (1.982 6 +/- 0.124 6) (P < 0.05), while IRS-1 mRNA (0.766 1 +/- 0.076 9) was up
      regulated (P < 0.05); HOMA-IR of group M (2.202 2 +/- 0.271 0) was higher than
      that of group C (P < 0.01), while IRS-1 mRNA (0.501 8 +/- 0.049 2) was suppressed
      (P < 0.01); HOMA-IR of group H (1.850 1 +/- 0.162 8) was not significantly
      changed as compared with that of group C (1.982 6 +/- 0.124 6) (P > 0.05), while
      IRS-1 mRNA (0.418 1 +/- 0.049 1) was significantly suppressed (P < 0.01). In male
      rats, the fasting plasma glucose and insulin had the similar change as those of
      female rats. The HOMA-IR of group M (1.878 5 +/- 0.250 2) was lower than that of
      C group (2.147 3 +/- 0.330 8) (P < 0.05), IRS-1 mRNA was up-regulated (0.824 9 +/
      0.064 7) (P < 0.05). CONCLUSIONS: The present study showed that low-to-moderate
      dose of alcohol could increase insulin sensitivity; while alcohol abuse could
      decrease insulin sensitivity. Sex difference in this effect was found. Changes of
      IRS-1 mRNA expression may be involved in the molecular mechanism of the effects
      of alcohol on insulin sensitivity.

PMID- 15498252
TI  - [Analysis of disease burden of diabetes mellitus in 1971-2000 in Shanghai].

PMID- 15498253
TI  - [Expression of hormone-sensitive lipase mRNA in diet-induced obesity resistant
      rats].
AB  - OBJECTIVE: In order to explore the expression of hormone-sensitive lipase (HSL)
      mRNA in white adipose tissue 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 DIO rats were selected according to their
      body weight and the quantity of energy intake, then observing changing of the
      body fat content, the level of serum growth hormone was determined by
      radioimmunoassay and the level of the HSL mRNA in white adipose tissue was
      determined by RT-PCR. RESULTS: The body fat content of DIO-R rats were lower than
      those of DIO rats (P < 0.05). The level of serum growth hormone of DIO-R rats
      were higher than those of DIO rats (P < 0.05). High fat diets increased the level
      of the HSL mRNA in DIO-R rats. CONCLUSION: Increasing expression of HSL in white
      adipose tissue may play a part of role in resisting diet-induced obesity of rats.

PMID- 15498254
TI  - [Discussing on" Suggestion of prevention and control of iodine deficiency in
      China"].

PMID- 15498255
TI  - [Progress in the study of human apurinic endonuclease].

PMID- 15498256
TI  - [Pseudo negative reaction in the detection of HIV antibodies in colloidal gold
      test and its resolving methods].

PMID- 15498257
TI  - [Progress in the study of food contamination with acrylamide].

PMID- 15498258
TI  - [Bacteria contamination of keyboard and mouse of computers for public using ].

PMID- 15498259
TI  - [Field investigation and prevention of severe acute respiratory syndrome].

PMID- 15498260
TI  - [Determination of Trace elements in Children by finger blood in London Town].

PMID- 15498262
TI  - [Effect of boletus aereous on blood lipids and antioxidant action in
      hyperlipidemia in rats].

PMID- 15498263
TI  - [Epidemiologic study of colon cancer in last 20 years in Tainjin].

PMID- 15498264
TI  - [Biological safety management of laboratory of severe acute respiratory
      syndrome].

PMID- 15498265
TI  - [Changes of angiotensin II and its receptor during the development of chronic
      intermittent hypoxia-induced hypertension in rats].
AB  - OBJECTIVE: To observe the changes of angiotensin II (ATII) and ATII type-1
      receptor (AT1R) during the development of chronic intermittent hypoxia (CIHO)
      induced hypertension in rats, and the effect in the mechanism of CIHO-induced
      hypertension. METHODS: Seventy-two male Wistar rats were divided into three
      groups:intermittent hypoxia group (IH), sham control group (SC) and control group
      (UC). By using supply of nitrogen (30 s each cycle) followed by compressed air
      (30 s each cycle) into the exposure chambers (4% - 6% nadir ambient oxygen with
      return to 21%), IH rats were subjected to intermittent hypoxia every 60 s for 8
      h/d during the diurnal sleep period. SC rats were similarly treated but received
      compressed air instead of nitrogen. UC rats were not treated. Mean arterial
      pressure (MAP), the levels of ATII and renin activity (RA) in plasma as well as
      the expression of AT1R mRNA in tissue were measured on day 7, 21 and 42 after
      experiment. RESULTS: MAP was significantly elevated in IH rats [(102.2 +/- 6.2)
      mm Hg, 1 mm Hg = 0.133 kPa] compared with initial MAP [(94.1 +/- 4.3) mm Hg, P <
      0.01] and compared with that in SC [(95.7 +/- 3.6) mm Hg], UC [(97.2 +/- 3.6) mm
      Hg, all P < 0.05] on day 42. The levels of ATII and RA in plasma in IH rats
      increased gradually over time, and RA started to increase significantly on day 7
      [(3.86 +/- 1.25) ng.ml(-1).h(-1)] compared with that in SC [(2.73 +/- 0.98)
      ng.ml(-1).h(-1)], UC [(2.55 +/- 0.87) ng.ml(-1).h(-1), all P < 0.05], and ATII
      started to increase significantly on day 21 [(214 +/- 41) ng/L] compared with
      that in SC [(124 +/- 21) ng/L], UC [(121 +/- 18) ng/L, all P < 0.01]. The RA and
      ATII levels in plasma showed positive correlation with MAP (r = 0.529, P = 0.008;
      r = 0.475, P = 0.019 respectively). The expression of AT1R mRNA in heart, kidney
      and aorta in IH rats showed no differences compared with that in SC and UC group
      (all P > 0.05). All indices were not different between SC and UC rats at any time
      point (all P > 0.05). CONCLUSION: CIHO can cause the levels of circulating RA and
      ATII to increase, but has no effects on AT1R mRNA expression in tissue, which
      suggests that activated renin-angiotensin system may contribute to the
      pathogenesis of CIHO-induced hypertension.

PMID- 15498266
TI  - [A prospective study on the cough mechanism induced by angiotensin-converting
      enzyme inhibitors in patients with hypertension].
AB  - OBJECTIVE: To explore the possible mechanisms underlying cough induced by
      angiotensin-converting enzyme inhibitors (ACEI) in patients with hypertension.
      METHODS: 127 patients with hypertension were enrolled to receive ACEI (97 cases
      prescribed cilazapril and 30 cases prescribed benazepril hydrochloride) for 8
      weeks. Patients who had coughed in the period were assigned to the cough group
      (48 cases) and patients who hadn't coughed were assigned to the non-cough group
      (79 cases). The serum ACE activity before and after administration of the drugs
      and the polymorphism of ACE gene (including homozygous-alleles II, DD, and
      heterozygous ID) were analyzed. Binary logistic regression was used as a
      statistical method to determine the factors associated with cough. RESULTS: The
      frequencies of the I alleles and II genotype of ACE gene in the cough group
      (0.70% and 56.3%) were significantly higher than those in the non-cough group
      (0.42% and 23.3%, P < 0.05). The mean serum ACE activity before and after
      administration of the ACEI in the cough group [(26 +/- 6) U/L, (4 +/- 4) U/L] was
      significantly lower than that in the non-cough group [(33 +/- 8) U/L, (8 +/- 8)
      U/L, all P < 0.01]. The difference in the range of decrease of serum ACE activity
      after ACEI between the cough group [(22 +/- 7) U/L] and the non-cough group [(25
      +/- 9) U/L] was not significant (P = 0.077). Serum ACE activity before ACEI was
      highest in the homozygous-alleles DD group [(36 +/- 8) U/L], secondly in the
      heterozygous ID group [(29 +/- 6) U/L] and the lowest in homozygous-alleles II
      group [(26 +/- 7) U/L], differences being significant among three groups (P <
      0.01). ACEI-related cough showed no relationship with sex, smoking habit and the
      ACEI used. CONCLUSIONS: The serum ACE activity was associated with polymorphism
      of ACE gene. Cough induced by ACEI was related to I allele and II genotype. There
      was a relationship between the serum ACE activity before administration of ACEI
      and cough induced by ACEI.

PMID- 15498267
TI  - [Expression of epidermal growth factor receptor and MUC5AC on human airway with
      chronic obstructive pulmonary disease].
AB  - OBJECTIVE: To determine the relationship between epidermal growth factor receptor
      (EGFR) expression and mucin 5AC (MUC5AC) synthesis in human airways with chronic
      obstructive pulmonary disease (COPD). METHODS: Lung specimens were obtained from
      38 patients who were undergoing lobectomy, and the samples were taken from areas
      remote to the lesion. EGFR and MUC5AC protein expression were examined using
      immunohistochemical analysis and Western blot in peripheral airways (less than 2
      mm in diameter) from 16 subjects with COPD, 10 subjects with a history of more
      than 30 pack-year smoking and 12 nonsmokers or exsmokers (0 - 10 pack-year
      smoker). RESULTS: Weak EGFR protein signals were detected in the lungs of the
      controls (2.01 +/- 1.02) in comparison with stronger signal in the COPD patients
      (4.62 +/- 1.65, P < 0.01) and the smokers (4.89 +/- 1.89, P < 0.01). EGFR
      immunoreactivity was observed mainly in goblet cells in the controls, the
      percentage of positive cell being 71.1% +/- 14.3%, which was higher than those in
      COPD (21.1% +/- 8.6%) or in the smoker (21.9% +/- 9.7%) airways. In contrast,
      COPD or smoker airways showed more expression of EGFR which expressed mainly in
      basal cells (42.9% +/- 14.2%, 52.1% +/- 13.5%, respectively) than that in the
      control airways (23.7% +/- 9.5%, P < 0.01). However there was no significant
      differences in EGFR expression and location in peripheral airways between COPD
      patients and smokers (P > 0.05). There was significant positive correlation
      between EGFR immunoreactivity and the area of the MUC5AC positive staining in all
      subjects (r = 0.877 4, P < 0.001). CONCLUSION: It is suggested that EGFR
      activation is involved in mucin expression in COPD airways.

PMID- 15498268
TI  - [Comparison of lateral position and prone position ventilation in patients with
      acute lung injury/acute respiratory distress syndrome].
AB  - OBJECTIVE: To evaluate the clinical result of lateral position ventilation and
      prone position ventilation in acute lung injury/acute respiratory distress
      syndrome (ALI/ARDS) patients. METHODS: Twenty-four patients were allocated to two
      groups, with one group (n = 13) receiving lateral position ventilation after
      April 2002, and the other (n = 11) received prone position ventilation before
      March 2002. Respiratory and circulatory indices were monitored after position
      changes and compared between the two groups. RESULTS: One hour after position
      change PaO(2) was elevated in both groups; in the lateral position group from
      (103 +/- 12) mm Hg to (126 +/- 13) mm Hg (P < 0.01), and in the prone position
      group from (87 +/- 19) mm Hg to (119 +/- 15) mm Hg (P < 0.01). If a 10 mm Hg
      increase was regarded as the standard of treatment effectiveness, then the
      effective rate in the lateral position group was 61.5% and in the prone position
      group was 63.6%, the difference being not significant. CONCLUSION: As auxiliary
      means in the treatment of ALI/ARDS, lateral position and prone position
      ventilation showed similar effects, but the lateral position was more convenient
      for practice and medical care, thus needs further investigation.

PMID- 15498269
TI  - [Acute respiratory failure and noninvasive positive pressure ventilation
      treatment in patients with severe acute respiratory syndrome].
AB  - OBJECTIVE: To describe the blood gas features and short-term outcomes of
      noninvasive positive pressure ventilation (NPPV) treatment for acute respiratory
      failure (ARF) in patients with severe acute respiratory syndrome (SARS) in this
      retrospective case series study sought. METHODS: Between April 22 and May 1,
      2003, 120 clinically compatible SARS patients were admitted to a special hospital
      for infectious diseases in Beijing. All patients' records were reviewed. The
      outcome variables of NPPV therapy were analyzed. RESULTS: At 6 weeks of SARS
      onset, 25% (30/120) patients had respiratory failure with ALI/ARDS. 16 (53%) had
      hypercapnia (PaCO(2) > 45 mm Hg) during the course of SARS. 28 of them received
      NPPV therapy. One was intolerable to NPPV treatment. In the remaining 27
      patients, NPPV was initiated 1.2 +/- 1.6 (0 - 10) days after onset of respiratory
      failure. One hour of NPPV therapy led to significant increases in PaO(2), SpO(2)
      and PaO(2)/FiO(2), and decrease in respiratory rate (all P < 0.01). 18 of the 27
      patients were weaned successfully from NPPV. The mean duration of NPPV use was 10
      +/- 6 (5 - 30) days. In addition to one patient who was intolerable to NPPV
      treatment, intubation was required in other 9 patients who initially had a
      favorable response to NPPV. Remarkable pulmonary barotrauma was noted in 7 of the
      120 (5.8%) patients with SARS, among which 1 developed 2 days after intubation,
      and 6 occurred while the patients were on NPPV, the incidence being 22% (6/27) in
      patients using NPPV. The fatality rate at 13 weeks of SARS onset was 6.7% (8/120)
      in the patient cohort, and 26.7% (8/30) in the ALI/ARDS patients. No SARS
      occurred in medical staff taking care of NPPV patients. CONCLUSIONS: Some of the
      SARS patients with ALI/ARDS could experience CO(2) retention, which might be
      related to the impairment of respiratory muscles. It is proved to be feasible and
      appropriate for NPPV treatment of respiratory failure in SARS patients who were
      at high risk of intubation related complications. As there was a high incidence
      of remarkable barotrauma, a careful lung protective strategy is necessary during
      the administration of NPPV as well as invasive mechanical ventilation.

PMID- 15498270
TI  - [Large-volume whole lung lavage in the treatment of severe pulmonary alveolar
      proteinosis].
AB  - OBJECTIVE: To evaluate the efficacy and safety of large-volume whole lung lavage
      in the treatment of severe pulmonary alveolar proteinosis (PAP). METHODS: Five
      severe PAP patients underwent large-volume whole lung lavage under general
      anaesthesia using a double lumen endotracheal tube. Suction was used for
      returning fluid. The volume of lavage and return volume and the return rate were
      calculated. The efficacy was evaluated according to the improvement of symptoms,
      amelioration of chest radiograph or chest CT scan and the changes of pulmonary
      function and artery blood gas analysis. RESULTS: After lavage, the symptoms,
      pulmonary function and artery blood gas were markedly improved, and the chest
      radiographs showed dissipation of lung consolidation. No severe complications
      were observed in the 5 cases. CONCLUSION: Large-volume whole lung lavage is an
      effective and safe therapeutic method in the treatment of PAP.

PMID- 15498271
TI  - [The significance of cell cycle distribution and expression of cell cycle
      regulatory proteins in T lymphocytes in patients with acute asthma attack].
AB  - OBJECTIVE: To explore the molecular regulatory mechanisms of excessive T
      lymphocyte activation and proliferation in patients with asthma attack by
      studying the cell cycle distribution and the expression of cell cycle regulatory
      proteins (CCRP) in peripheral blood T lymphocytes. METHODS: DNA of T lymphocytes
      from 30 patients with asthma attack and 20 normal subjects was stained with
      propidium iodide, and the cell cycle distribution was analyzed by flow cytometry.
      By indirect immunofluorescence, the expressions of P27kipl, cyclin E, cyclin A,
      and cyclin B in T lymphocytes were measured by flow cytometry. The difference
      between patients with asthma attack and normal subjects was analyzed. RESULTS:
      The percentage of T lymphocytes in the S phase and S + G(2)/M phase was (18 +/-
      9)% and (25 +/- 10)% respectively in the asthma group, which were significantly
      higher than those in the control group [(5 +/- 4)%, (11 +/- 6)%, all P < 0.01
      respectively]. The percentage of T lymphocytes in the G(0)/G(1) phase in the
      asthma group was (76 +/- 10)%, which was significantly lower than that in the
      control group [(90 +/- 6)%, P < 0.01]. The expression of P27kipl in T lymphocytes
      of the asthma group (4.0 +/- 2.4)% was lower than that of the control group [(6.7
      +/- 4.8)%, P < 0.05]. The expression of cyclin E, cyclin A, and cyclin B in T
      lymphocytes of the asthma group [(25 +/- 24)%, (9 +/- 7)% and (6.4 +/- 5.9)%,
      respectively] were significantly higher than those of the control group [(6 +/-
      5)%, (4 +/- 4)% and (3.4 +/- 1.6)% respectively], the differences being all
      statistically significant (all P < 0.01). CONCLUSIONS: The abnormal expression of
      CCRP in T lymphocytes was related to the excessive activation and proliferation
      of T lymphocytes in patients with asthma attack. A new approach to asthma therapy
      may be developed with CCRP as a regulatory target.

PMID- 15498272
TI  - [Preliminary research on the effect of antisense oligodeoxynucleotides of
      tankyrase 1 on tumor growth following intratumoral injection in mice].
AB  - OBJECTIVE: To observe the suppressing effect of antisense oligodeoxynucleotides
      of tankyrase 1 (TANK1-ASODN) on murine tumor growth following intratumoral
      injection, and to explore its potential use in clinical treatment of lung cancer.
      METHODS: After human lung cancer cells CALU had been inoculated subcutaneously to
      BALB/c nude mice and grew to tumor nodules, these mice were distributed randomly
      into three groups: four in the saline group, five in the TANK1-ASODN group, and
      another five in the sense oligodeoxynucleotides of tankyrase (TANK1-SODN) group.
      Multiple direct intratumoral injections of TANK1-ASODN, TANK1-SODN or saline were
      given into the tumor nodules, respectively. The tumor growth and the
      histopathological characteristics were observed and the expression of ki67 and
      telomerase hTERT in tumor cells were measured by SABC immunohistrochemical
      method. RESULTS: After 16 days of continuous injection, the tumor volume of the
      TANK1-ASODN group was significantly smaller than that of the TANK1-SODN (P <
      0.01) and saline-treated groups (P < 0.01); tumor cell degeneration and necrosis
      were observed in mice treated with TANK1-ASODN. Moreover, a statistically
      significant decrease in Ki67 labeling index (P < 0.01) and the positive
      expression ratio of telomerase hTERT (P < 0.01) was observed in the TANK1-ASODN
      group. CONCLUSIONS: Human lung tumor cell lines express high telomerase activity.
      TANK1-ASODN can inhibit the activity of telomerase and suppress the proliferation
      of tumor cells.

PMID- 15498273
TI  - [Diffuse panbronchiolitis complicated by thymoma: a case report and a review of
      literature].
AB  - OBJECTIVE: To highlight the characteristics of diffuse panbronchiolitis (DPB).
      METHOD: One patient with DPB confirmed by thorocoscopic biopsy was described and
      relevant literatures were reviewed. RESULTS: DPB is a chronic lower respiratory
      tract disease common in Japanese, rare in China, characterized by infiltration of
      inflammatory cells around bronchioles. Although the etiology and precise
      mechanisms are under investigation, it is commonly hypothesized that heredity and
      immunity have a major role in DPB. Symptoms include cough, expectoration, and
      dyspnea after exercises. Pseudomonas aeruginosa is isolated from sputum in some
      cases. If left untreated, DPB progresses rapidly and has a poor prognosis if
      respiratory failure occurs. CONCLUSIONS: DPB should be included in the
      differential diagnosis of bilateral multiple pulmonary nodular shadows. Long
      term, low-dose macrolide therapy may improve the prognosis through an anti
      inflammatory effect.

PMID- 15498274
TI  - [A study of the protective effect of the DNA vaccine encoding tubercle antigen
      85B with MPT64 in mice challenged with Mycobacterium tuberculosis].
AB  - OBJECTIVE: To explore the protective effect of the DNA vaccine encoding
      Mycobacterium tuberculosis Ag85B with MPT64 in mice infected with Mycobacterium
      tuberculosis. METHODS: Fifty four C57BL/6 mice were randomized into six groups
      and subjected to the following treatments respectively: intramuscularly immunized
      with PBS, pcDNA3.1, BCG, pcDNA/Ag85B, pcDNA/MPT64 and pcDNA/Ag85B + pcDNA/MPT64
      on three occasions at 3-week intervals. The BCG group received a single
      subcutaneous injection of 1 x 10(6) CFU BCG. The mice were challenged with 10(6)
      CFU H(37)Rv via lateral tail vein 35 days later after the third immunization for
      DNA vaccine groups and 100 days later for BCG vaccinated group. The mice in
      vaccinated groups and control groups were sacrificed 42 days later following
      challenge. The lungs and spleens were removed, and the number of CFU in organs
      and histopathologic changes were determined. The antibody level, IFN-gamma, IL-4
      and the survival time in all of the mice were evaluated. RESULTS: The number of
      bacterial colonies in the lungs and spleens were lg(-1) (7.854 +/- 0.003) CFU/g
      and lg(-1) (7.190 +/- 0.016) CFU/g in PBS group, lg(-1) (7.700 +/- 0.016) CFU/g
      and lg(-1) (7.072 +/- 0.068) CFU/g in pcDNA3.1 group, lg(-1) (6.449 +/- 0.002)
      CFU/g and lg(-1) (5.436 +/- 0.042) CFU/g in BCG group, lg(-1) (7.370 +/- 0.002)
      CFU/g and lg(-1) (6.430 +/- 0.009) CFU/g in pcDNA/Ag85B group, lg(-1) (7.547 +/-
      0.003) CFU/g and lg(-1) (6.784 +/- 0.002) CFU/g in pcDNA/MPT64 group, and lg(-1)
      (6.918 +/- 0.002) CFU/g and lg(-1) (6.079 +/- 0.004) CFU/g in pcDNA/Ag85B +
      pcDNA/MPT64 group respectively, which showed significant decrease at 6th week
      postchallenge in all the vaccinated groups (P < 0.05), especially in BCG group (P
      < 0.01). Antibody titer of pcDNA/Ag85B + pcDNA/MPT64 group and pcDNA/Ag85B group
      was higher than that of the other groups (P < 0.05). The level of IFN-gamma
      produced by spleen lymphocytes and spleen lymphocyte proliferation from BCG
      group, pcDNA/Ag85B + pcDNA/MPT64 group was higher than that of the other groups
      (P < 0.05). No IL-4 was detected in all groups. The pulmonary histopathological
      changes were observed 6 weeks later following challenge with Mycobacterium
      tuberculosis H(37)Rv. In PBS and pcDNA3.1 groups, the lesion was characterized by
      inflammatory infiltration and lung tissue necrosis, in BCG group by granulomas
      and numerous macrophages, lymphocytes and a few epithelioid cells. The lesion in
      pcDNA/Ag85B group was characterized by serofibrous inflammatory infiltration and
      a few macrophages, in pcDNA/Ag85B + pcDNA/MPT64 group, by granulomas, numerous
      macrophages and lymphocytes. The lesion in spleen was different from the lung and
      characterized by proliferative lymphocytes and inflammatory infiltration. The
      results in spleen were similar to those in the lung. The survival time of BCG
      vaccinated mice after challenge with Mycobacterium tuberculosis H(37)Rv was
      longer than that of the other groups. The survival time of pcDNA/Ag85B +
      pcDNA/MPT64 group was longer than that of other DNA vaccine groups. CONCLUSION:
      The protective effect of BCG was more significant than the other groups, while
      the effect of pcDNA/Ag85B + pcDNA/MPT64 was better than other DNA vaccines.

PMID- 15498275
TI  - [Factors associated with diagnostic delay for patients with smear-positive
      pulmonary tuberculosis in rural Hunan, China].
AB  - OBJECTIVE: To explore the influences of socio-economic, health services, cultural
      beliefs, and symptoms on health seeking behavior of tuberculosis patients
      attending county tuberculosis dispensaries in rural Hunan province of China.
      METHODS: A cross-sectional descriptive survey was conducted in 4 counties
      randomly stratified by economic status from 122 counties, Hunan, China. After
      informed consent, a consecutive sample of patients, aged 15 years and older, with
      smear-positive pulmonary tuberculosis were interviewed and completed a pre-tested
      questionnaire. RESULTS: A total of 318 patients with smear-positive pulmonary
      tuberculosis were interviewed. The median of patient delay, health system delay
      and total delay were 30, 24 and 65 days, respectively. Logistic regression shows
      that factors significantly contributed to patient delay were haemoptysis, far
      distance to health institute, seeking folk therapy, and lower per capita income.
      Factors significantly associated with health system delay were female, lower
      level of education, prior health education on tuberculosis, seeking folk therapy
      and stigma associated with tuberculosis. CONCLUSION: In order to reduce
      diagnostic delay, integrated measures including extensive training of medical
      staff in non-tuberculosis health facilities, decentralization of services and
      more specific and effective health education on tuberculosis should be taken.

PMID- 15498276
TI  - [The genetic polymorphisms of the enzymes involved in the leukotrienes formation:
      relationship with asthma].

PMID- 15498277
TI  - [TASK-1, an acid-sensitive K+ channel may modulate respiration and its clinical
      significance].

PMID- 15498278
TI  - [The relationship between cystic fibrosis and bronchiectasis and its research
      implications in Chinese].

PMID- 15498292
TI  - [The discussion of standards for clinical functional gradation and preoperative
      preparation of pheochromocytoma].
AB  - OBJECTIVE: To discuss the standards for clinical functional gradation and
      preoperative preparation of pheochromocytoma. METHODS: According to the
      preoperative clinical manifestations and 24 hr urine catecholamine, 172 cases of
      pheochromocytomas were divided into 4 grades. Functionary grade 0 including 22
      patients was given no volume expansion. Functionary Grade 1 consisted of 17
      cases, 10 of which were given phenoxybenzamine orally 5 - 10 mg/d for 1 week
      (therapeutic group), the rest were control group; the results were analyzed by
      the chi(2) test. Functionary Grade 2 including 120 patients had phenoxybenzamine
      orally 30 - 240 mg/d for 4 weeks, hemodynamics and microcirculation image were
      standards for evaluating volume expansion. Functionary Grade 3 consisted of 13
      patients including 1 with acute heart failure, 2 and 10 patients with past
      history of cerebral hemorrhage and hypertensive crisis respectively, they were
      treated with enough phenoxybenzamine and other emergent measures. RESULTS: The
      perioperative blood pressure of Functionary Grade 0 had no fluctuation. The blood
      pressure of therapeutic group of Functionary Grade 1 had small range fluctuation
      (< 20 mm Hg), that of the control group was large (> 40 mm Hg). Chi(2) = 13.12, P
      < 0.01. The hemodynamics of Functionary Grade 2 and Grade 3 recovered within 24
      hours postoperatively and no complications occurred. CONCLUSION: According to the
      function of pheochromocytoma, it is safe and efficient to use different
      preoperative preparations. Hemodynamics and microcirculation image are golden
      standards for evaluating preoperative preparations.

PMID- 15498293
TI  - [Retroperitoneal laparoscopic management of primary aldosteronism with report of
      130 cases].
AB  - OBJECTIVE: To evaluate retroperitoneal laparoscopic partial or total
      adrenalectomy for primary aldosteronism. METHODS: From February 2000 to September
      2003, 130 patients (76 women and 54 men) with a confirmed diagnosis of primary
      aldosteronism underwent retroperitoneal laparoscopic operation. Of the 130 cases,
      there were 119 cases with Aldosterone-producing Adenoma and 11 cases with
      Idiopathic Adrenal Hyperplasia (unilateral of 2 cases). Eleven cases with
      Idiopathic Adrenal Hyperplasia underwent unilateral adrenalectomy. Of the 119
      cases with Aldosterone-producing Adenoma, 61 cases underwent total adrenalectomy,
      and 58 cases underwent partial adrenalectomy. All cases were with preoperatively
      high plasma aldosterone, low plasma rennin and hypokalemia and arterial
      hypertension. RESULTS: Operations were successfully performed in all cases. The
      operative time ranged from 15 to 225 min (mean 52 +/- 40 min, Md = 43 min) and
      the operative bleeding ranged from 0 to 200 ml (mean 23 +/- 34 ml, Md = 20 ml,
      zero bleeding means that less than 5 ml) without blood transfusion. The hospital
      length of stay was ranged from 3 to 9 d (mean 5.1 +/- 1.3 d). No major
      complication occurred. Kalemia was normalized within one month and
      aldosterone/PRA ratio was decreased obviously in all cases. Postoperatively blood
      pressure was normalized within 2 month in 88 cases without using any drug.
      CONCLUSION: It is safe and practical to perform retroperitoneal laparoscopic
      partial on total adrenalectomy on the patients with primary aldosteronism.

PMID- 15498294
TI  - [The clinical characteristics and therapy of multiple endocrine neoplasia type
      2].
AB  - OBJECTIVE: To study the clinical characteristics and treatment of multiple
      endocrine neoplasia (MEN) type 2. METHODS: The clinical features, diagnosis and
      treatment of from 1980 to 2002 8 cases of multiple endocrine neoplasia type 2
      from Peking Union Medical College Hospital were reviewed and analyzed in clinical
      features, diagnosis and treatment retrospectively. RESULTS: Seven cases were with
      paroxysmal hypertension, the highest blood pressure was over 200 mm Hg (1 mm Hg =
      0.133 kPa). Tumor was found in 3 cases. The diagnosis was confirmed by B
      ultrasonography, CT and urine catecholamine test: six cases with MEN 2a 2 with
      MEN 2b. Six cases were medullary carcinoma of thyroid with or without
      parathyroidoma or hyperplasia, 1 with multiple mucosal neuromata. One case was
      pheochromocytoma with marfan's syndrome; 7 cases were with bilateral adrenal
      tumor. Total resection or resection ectomy was performed on different stages on
      adrenal gland, parathyroid tubercle. Average follow-up was 9 years. And the
      feedback was good. CONCLUSION: The diagnosis of multiple endocrine neoplasia type
      2 depends on endocrine biochemical tests, B-ultrasonography and CT. When the
      pheochromocytoma and the other tumor exists at the same time, operation is the
      primary treatment, and it is better to remove the pheochromocytoma at the first.

PMID- 15498295
TI  - [Pediatric renal transplantation: clinical analysis of 23 cases].
AB  - OBJECTIVE: To study the clinical characters and the therapeutic experience of
      pediatric kidney transplantation. METHODS: Clinical data of 23 pediatric renal
      transplant recipients (less than 18 years, 14 boys, 9 girls) were analyzed.
      Recipients were 11 - 17 (mean 15.4 +/- 1.0 years) years old at transplantation.
      The kidneys were transplanted en bloc extraperitoneally into the recipient's
      iliac fossa, with the donor renal vein anastomosed to the recipient's external
      iliac vein. Among 23 transplant procedures, the donor renal artery was
      anastomosed to the external iliac artery in 14 cases, to the internal iliac
      artery in 4 cases and to the common iliac artery in 3. The other two allografts
      were unusual. All the patients were treated with cyclosporine or tacrolimus based
      immunosuppression, including steroid and azathioprine or mycophenolate mofetil.
      The initial dose of cyclosporine was 6 - 7 mg per kilogram of body weight per day
      and that of tacrolimus was 0.15 - 0.20 mg per kilogram of body weight per day.
      The data of the recovery of renal function, rejection episodes, incidences of
      side effect and related complication were analyzed respectively. RESULTS: The
      transplantation operations were performed uneventful in all the 23 recipients.
      There were no graft losses for technical reasons. The single graft failure was
      the result from bad compliance. The renal function was improved 5.5 days in
      average after transplantation in 22 cases. Main complications were arterial
      hypertension (57%), pulmonary infection (13%), drug-induced hepatic injury (13%)
      and bone marrow suppression (13%). Acute rejection occurred in 4 persons 1 year
      post-operatively (17%). The body weight of the recipients increased 2.3 kg in
      average and height increased 1.0 cm after the first post-operative year. The mean
      duration for follow-up was 42 month. One-year patient/graft survival rate was
      100%/96% and three-year patient/graft survival rate was 90%/80%. CONCLUSION:
      Kidney transplantation is the preferred treatment for end stage renal failure in
      children patient. The well procedure, reasonable immunosuppressive regime,
      prevention and prompt therapy of complication are the keys to get satisfactory
      survival rate of human/kidney.

PMID- 15498296
TI  - [The significance of the expression of cyclooxygenase-2 in bladder transitional
      cell carcinoma tissues].
AB  - OBJECTIVE: To investigate the expression of cyclooxygenase-2 (COX-2) in bladder
      transitional cell carcinoma tissues, and understand its clinical significance.
      METHODS: Reversal transcription polymerase chain reaction (RT-PCR) was used to
      assess the expression of COX-2 mRNA in 52 cases of bladder transitional cell
      carcinoma tissues and 17 cases of normal bladder tissues far from neoplasm;
      Western blot was used to assess the expression of COX-2 protein in 49 cases of
      bladder cancerous tissues and 17 cases of normal tissues. RESULTS: Positive
      expression of COX-2 mRNA was detected in 83% (43/52) of bladder cancer tissues
      and in 29% (5/17) of normal tissues by RT-PCR and there was significant
      difference in expression of COX-2 mRNA between cancer tissues and normal tissues.
      Western blot analysis showed that expression of COX-2 protein was correlation
      with the stage and grade of cancer. CONCLUSION: COX-2 is overexpressed in bladder
      transitional cell carcinoma. COX-2 maybe play a certain role in carcinogenesis
      and progression of bladder cancer and turn into a useful target of
      chemoprevention of bladder cancer.

PMID- 15498297
TI  - [The heat shock protein 70 antisense oligomers enhance the sensitivity of bladder
      cancer cell EJ to mitomycin C].
AB  - OBJECTIVE: To investigate whether the heat shock protein (HSP) 70 antisense
      oligomers can enhance the sensitivity of bladder cancer cell EJ to mitomycin C.
      METHODS: The HSP70 mRNA of EJ cells was blocked by the 10 micromol/L HSP70
      antisense oligomers, while its effect on cell growth was evaluated by methyl
      thiazolyl tetrazolium (MTT) and colony forming ability test. RESULTS: The HSP70
      expressions in HSP70 antisense treated group were lower than the corresponding
      sense and nonsense treated groups (P < 0.01). While, the increased sensitivity of
      EJ to mitomycin C was found in antisense treated group, compared with the
      corresponding sense and nonsense treated groups (P < 0.01). CONCLUSION: The
      sensitivity of bladder cancer cell EJ to mitomycin C was enhanced by the blockage
      of the HSP70 expression.

PMID- 15498298
TI  - [Comparative studies of the expression of estrogen receptor-alpha and estrogen
      receptor-beta in prostatic carcinoma].
AB  - OBJECTIVE: To determine the expression of estrogen receptor-alpha (ERalpha) and
      estrogen receptor-beta (ERbeta) in prostatic carcinoma (PCa). METHODS: The
      expression of ERalpha and ERbeta was analysed in 32 cases of PCa, 12 cases of
      normal prostate tissue and 32 cases of benign prostate hyperplasia (BPH) by semi
      quantitative reverse transcriptase polymerase chain reaction (RT-PCR), and the
      genes were sequenced. RESULTS: Compared with the tissue of BPH, the ERalpha
      expression significantly increased, but the ERbeta expression decreased in the
      tissue of PCa (P < 0.01). Compared with in the early stage and high
      differentiation of prostatic carcinoma, the ERalpha expression increased
      obviously, but ERbeta expression decreased in the developed stage and low
      differentiation (P < 0.01). ERalpha increased, but ERbeta decreased in hormone
      refractory prostatic carcinoma (P < 0.05). CONCLUSION: ERalpha and ERbeta may
      play an important role in the development of PCa. It is shown that analysis of
      the expression of ER, especially ERbeta in PCa, will benefit to the diagnosis and
      treatment of this disease.

PMID- 15498299
TI  - [Exploration on endovascular treatment for disorders of great vessels].
AB  - OBJECTIVE: To explore the efficacy and shortcoming of endovascular therapy with
      mainly endovascular graft in treating disorders occurring in the thoracic or
      thoracoabdominal aorta. METHODS: Total 137 cases with great vessel disorders
      including dissections, aneurysm, pseudoaneurysm, aortic deceleration injury and
      coarctation were treated by endovascular technique. The lowest lesion located
      between the celiac and mesenteric arteries. RESULTS: Two cases underwent emergent
      surgery due to acute visceral arterial insufficiency. Seven cases had early
      endoleaks. After a follow-up of 1 - 43 (average of 11) months, 2 late endoleaks
      were detected; 5 patients died, 4 of them were due to endograft unrelated
      diseases, one due to a recurrent multiple aneurysms. CONCLUSION: Endovascular
      treatment is relatively safe and effective for treating high risky patients with
      lesions occurring in the great vessels and seems to have a prospective future,
      although the device needs to be further improved and the long-term efficacy
      should be confirmed.

PMID- 15498300
TI  - [The evaluation for the therapeutic effect and the clinical practicability of
      encircling constriction of superficial femoral vein in the treatment of primary
      deep venous insufficiency].
AB  - OBJECTIVE: To evaluate the therapeutic effect and the clinical practicability of
      encircling constriction of superficial femoral vein in the treatment of primary
      deep venous insufficiency (PDVI). METHODS: Ninety-seven limbs in 97 patients who
      were proved to be PDVI by ascending venography were divided into Group A (79
      limbs) and Group B (18 limbs). Patients of Group A were treated with the
      encircling constriction of venous wall at the first valve of superficial femoral
      veins. And they were also treated with the high ligation and ablation of great
      saphenous vein, ablation of superficial veins and ligation of perforator veins at
      the same time. Patients of Group B were simply treated with the high ligation and
      ablation of great saphenous vein, ablation of superficial veins and ligation of
      perforator veins. Ascending venography and CEAP classification and clinical
      scoring were proceeded from two months to six years after operation to evaluate
      the effect of the operation. RESULTS: The difference between preoperative and
      postoperative scores of Group A and Group B were both remarkable (Group A, P <
      0.01; Group B, P < 0.05). The difference of scores, which equated to preoperative
      scores minus postoperative score, between Group A and Group B were also prominent
      (P < 0.01). Post-operation ascending venography was performed on 67 limbs in
      Group A. The effective rate of the operation is 83.58% (28 + 28/67), obviously
      effective rate is 41.79% (28/67). Same exam was performed on 12 limbs in Group B
      and the effective rate of the operation is 33.33%. The difference between two
      groups' effective rate is significant (P < 0.05). CONCLUSIONS: Clinical scoring
      of Group A decreased much more than Group B; The effective rate of Group A in
      ascending venography is also much higher than Group B. Encircling constriction of
      superficial femoral vein is useful to relief the symptom and recover the shape
      and function of the valve of superficial femoral veins. Those who are diagnosed
      to be PDVI by means of pre-operation ascending venography and Valsalva test
      should accept the operation of the encircling constriction of superficial femoral
      vein.

PMID- 15498301
TI  - [Endovenous laser treatment of 62 patients with primary varicose veins of lower
      extremities].
AB  - OBJECTIVE: To retrospectively analyze the experiences and results of the
      treatment on 62 patients with primary varicose of lower extremities with
      endovenous laser. METHODS: All patients were treated with endovenous laser. The
      laser treatment could begin when the fiber withdraw with 1 cm/2 s. The laser
      power was 10 - 12 w with the laser pulse duration and the interval 1 second
      respectively. RESULTS: The duration of follow-up varied from 2 months to 8
      months. After endovenous treatment, the varicose veins and edema disappeared in
      all cases. The itching and uncomfortable feeling was dissipated. No morphine-like
      analgesic has been used and no serious complications occurred. CONCLUSION:
      Endovenous laser treatment of primary varicose of lower extremities is a safe and
      effective technique.

PMID- 15498302
TI  - [The clinical classification and treatment of arteriovenous malformations of
      maxilloface].
AB  - OBJECTIVE: To explore the clinical classification and ideal therapy for
      maxillofacial AVMs. METHODS: According to the clinical characteristics, 106
      patients with maxillofacial AVMs were divided into the 4 types Of them, 38 cases
      were cystic dilatation lesions, 22 cases were limited thicken lesions, 42 case
      were diffuse thicken lesions, 4 cases were central maxillary hemangioma. 106
      patients with maxillofacial AVMs were treated in our hospital, of them, 8 cases
      received operation (group 1); 23 cases received embolization of supplying artery
      alone (group 2); 37 cases received embolization of supplying artery plus hardener
      intra-tumorous injection (group 3); 38 cases received embolization of supplying
      artery plus tumor resection (group 4). RESULTS: Of all the patients were followed
      up 1 - 11 years, In group 1, 2, 3, and 4, the cure rates is 62.50%, 17.39%,
      89.19%, and 97.37% respectively. one patient died of embolization of abnormal
      communication branches between external carotid and intra-cranical arteries.
      CONCLUSIONS: (1) This new clinical classification is beneficial for selecting
      method of treatment. (2) It is necessary that a good digital subtraction
      angiography for maxillofacial AVMs. (3) The embolization of tumor supplying
      artery alone could cure the small AVM with single branch terminal blood supply.
      (4) The embolization of supplying artery plus hardener intratumorous injection or
      the embolization of supplying artery plus tumor resection is an effective method
      for maxillofacial AVMs.

PMID- 15498303
TI  - [Clinicopathologic features of kaposiform hemangioendothelioma].
AB  - OBJECTIVE: To explore the clinicopathologic features of kaposiform
      hemangioendothelioma (KHE). METHODS: The clinicopathologic data were studied in
      three cases of KHE and review the literatures. RESULTS: Two cases were female and
      one was male. All cases occurred in infancy. Two tumor located in axillary chest
      wall and one in lumbar region. All of the three patients had Kasabach-Merritt
      syndrome. Histologically, the tumor was composed of spindle-shaped cells. in all
      cases nodular growth pattern was seen. Immunohistochemically, Neoplastic spindled
      cells expressed CD34 and CD31. Associated lymphangiomatosis was present in two
      cases. Two tumors were resected completely, one was resected partly. the follow
      up period ranged from 6 months to 3 years, and all were alive. CONCLUSIONS:
      Kaposiform hemangioendothelioma is a rare locally aggressive vascular tumor that
      mainly occurred in early infancy. It is frequently complicated by Kasabach
      Merritt syndrome, and it has features common to both capillary hemangioma and
      Kaposi sarcoma. The prognosis of KHE is determined by the size, location and the
      hemorrhage degree of vascular tumor. Better outcome might be achieved in patients
      with KHE of the skin and in the soft tissues under the skin. It appears that the
      main treated measure should be wide local excision.

PMID- 15498304
TI  - [Study on the potentiation of bone marrow mesenchymal stem cells involved in
      sebaceous duct formation].
AB  - OBJECTIVE: To investigate the feasibility of differentiation of bone marrow
      mesenchymal stem cells (MSCs) into skin appandence. METHODS: Porcine MSCs were
      isolated from porcine marrow and grown in vitro. After labeling with BrdU, MSCs
      were engrafted to porcine skin. At 1, 2, 4 weeks after the transplantation,
      immunohistochemical examinations were carried out to detect the positive staining
      of BrdU and cytokeratin. RESULTS: A few sebaceous duct cells, which expressed
      cytokeratin, were also BrdU positive, and these cells were considered may to be
      transplanted MSCs-derived cells. CONCLUSION: Porcine MSCs might have the
      potential to differentiated into sebaceous duct cells in skin.

PMID- 15498305
TI  - [One-stage reconstruction of bilateral mandibular with free fibula flap].
AB  - OBJECTIVE: To explore the method of clinical application and the efficacy of free
      fibula osteomyocutaneous flap in one-stage reconstruction of transmidline
      bilateral mandibular defect caused by giant neoplasms. METHODS: From july 2000 to
      october 2002, transmidline bilateral mandibular defects caused by ameloblastoma
      (4 cases) and gingival carcinoma (2 cases), according to the character of
      defects, were reconstructed with free fibula osteomyocutaneous flaps. Peroneal
      artery and vein were used as vascular pedicle, the fibula was reshaped, and micro
      titanium plates were used in rigid fixation between fibula and residue of
      bilateral mandible. Microvascular anastomoses were carried out between peroneal
      artery/vein and small artery/vein in neck. RESULTS: Six free fibular
      osteomyocutaneous flaps survived well. Follow up duration ranged from 6 months to
      2 years, the lower face appearance recovered well, occlusion relationship were
      normal, all patients were satisfactory with appearance and chewing function after
      repair of removable denture. CONCLUSION: Free fibular osteomyocutaneous flap is a
      favorable material in the reconstruction of transmidline bilateral mandibular
      giant defect. The blood supplement of fibula is offered both by segmentral
      periosteum and nutrient artery from bone marrow, It is greatly benefit to
      reshaping as arched mandible.

PMID- 15498306
TI  - [Effects of escharectomy during burn shock stage on the mRNA expression of IFN
      gamma and IL-4 in spleen T lymphocytes in rats after thermal injury].
AB  - OBJECTIVE: To determine the serum level and mRNA expression of type-1/type-2
      cytokines of T lymphocytes in spleens of rats after thermal injury and to
      investigate the effects of escharectomy during burn shock stage on IFN-gamma and
      IL-4. METHODS: One hundred and sixty male Wistar rats were randomized into four
      groups. In group A, animals were not subjected to escharectomy. In groups B, C
      and D, escharectomy and skin allograft were performed at 8, 24, 96 hours postburn
      (PB) respectively. At 4, 12, 24, 48, 96, 120 and 168 hours PB, animals were
      killed and blood and spleens samples were harvested. ELISA was applied to
      determine the concentration of IFN-gamma and IL-4 in serum. The expression
      pattern of IFN-gamma and IL-4 were observed at mRNA level in T lymphocytes
      isolated from spleen by RT-PCR. RESULTS: The serum level of IFN-gamma and IL-4
      rose rapidly and significantly after scald injury, expression of IFN-gamma and IL
      4 mRNA in rats' T lymphocyte were also up-regulated spontaneously. The serum
      level of IFN-gamma and its mRNA expression began to rise within 4 hours PB,
      peaking at 24 hours PB. Whereas IL-4 and its mRNA expression showed a persistent
      elevation. Thereby leading to a dominant tendency of Th2 cytokine response on 7 d
      PB. In group A all above parameters revealed most obvious changes compared with
      controls, then ranked in group D, B and C. CONCLUSION: Escharectomy during burn
      shock stage is helpful to decrease the harmful over expression of Th2-type
      lymphocyte after severe thermal injury.

PMID- 15498311
TI  - [Surgical treatment for the giant hepatic carcinomas occupying the central part
      of the liver].
AB  - OBJECTIVE: To evaluate the techniques and the effects of surgical resection of
      giant hepatic carcinomas which occupied the central part of the liver. METHODS: A
      retrospective study was carried out of hepatectomies performed for central giant
      hepatic carcinomas. The hepatic tumors included in this study were hepatocellular
      carcinomas, cholangiocarcinomas and hepatic metastases which situated in the
      central part of the liver (segment IV, V, VIII, I) with a diameter of larger than
      10 cm and involved hepatocaval confluence, retrohepatic inferior vena cava (IVC)
      as well as hepatic portal. RESULTS: A total of 40 central giant hepatic
      carcinomas were successfully resected, with a mean diameter of 13.6 cm (range
      10.5-19.0 cm). The types of the hepatectomies conducted were as follows: extended
      mid-hepatectomy in 9 cases, atypical mid-hepatectomy in 13 cases, extended left
      hepatectomy in 13 cases, total caudatectomy plus extended left hepatectomy in 3
      cases and extended right hepatectomy in 2 cases. The mean operation time was 197
      min (range 90 - 380 min) and the mean intraoperative blood lose 1,596 ml (range
      300-11,000 ml), with operative mortality and morbidity being 0 and 20%,
      respectively. The postoperative 1, 3 and 5 year survival rates for the patients
      were 88%, 56% and 28%, respectively. CONCLUSIONS: The hepatic carcinomas of
      central type, when larger than 10 cm in diameter, frequently involves all the
      hepatic portal, hepatocaval confluence and retrohepatic IVC. Surgical resection
      of this kind of tumor, though sophisticated in technique, is safe and effective
      and, therefore, the first choice of the treatments.

PMID- 15498312
TI  - [Ultrasound-guided percutaneous composite thermal ablation technique in treatment
      of medium and large hepatocellular carcinoma].
AB  - OBJECTIVE: To evaluate the clinical values of ultrasound-guided percutaneous
      composite thermal ablation technique in the treatment of medium and large
      hepatocellular carcinoma (HCC). METHODS: By the composite technique of multiple
      needle insertion and multi-point energy application, ultrasound-guided
      percutaneous radiofrequency ablation (RFA) or microwave ablation (MWA) were
      employed to treat 68 patients of HCC with tumor nodule > or = 3.1 cm in diameter.
      There was a total number of 73 tumor nodules, with a mean diameter of (4.5 +/-
      1.7) cm (3.1-13.0 cm). Sixty-three patients had single tumor nodule, and the
      remaining 5 had 2 nodules. With a follow-up time of 1.9 - 67.6 months [(16.0 +/-
      14.8) months], the local and long-term efficacy was analyzed. RESULTS: Hepatic
      subcapsular hematoma were found in 1 patient. And skin burning in 1 patient 1.
      Complete ablation rate was 78.1% (57/73), local tumor progression was presented
      in 24.6% tumor nodules (14/57) and distant recurrence developed in 56.7% patients
      (38/67). The 1-, 3-, 5-years survival rate was 62.3%, 29.6% and 21.6%,
      respectively, with a median survival time of 18.6 months, (95% confidence
      interval: 10.9 months, 26.3 months). There were no remarkable differences in
      complete ablation rate, local tumor progression, distant recurrence rate and
      survival rate between RFA and MWA. CONCLUSIONS: By the composite ablation
      technique, ultrasound-guided percutaneous thermal ablation was effective in
      treating medium and large unresectable HCC. And the advantage is minimal
      invasiveness. RFA and MWA had no marked differences in terms of therapeutic
      efficacy.

PMID- 15498313
TI  - [Segmentectomy for hepatoma originated from segment IX].
AB  - OBJECTIVE: To report the procedure of segmentectomy for hepatoma located in
      segment IX. METHODS: 11 cases of hepatoma originated from segment IX were treated
      by segmentectomy without interruption of blood flow of the liver. Among total 11
      cases, 10 cases were primary liver cancer, the other one was secondary liver
      cancer. RESULTS: Tumor diameters from 6 to 14 cm (median 9.2 cm), no
      perioperative death occurred in this group. Intraoperative blood losses were 200
      600 ml (median 350 ml) without severe postoperative complications. Postoperative
      hospitalization time were 9-14 days (median 11 days). Transhepatic artery
      chemoembolization (TACE) was given at 4-6 weeks after operation and repeated at
      intervals of 2 to 4 months for 1 year. During the follow up time of 5-29 months
      (media 17 months), 10 patients were tumor-free and 1 patient developed an
      intrahepatic metastasis. CONCLUSIONS: Segmentectomy without interruption of blood
      flow of the liver is safe and practical for hepatoma located in segment IX.

PMID- 15498314
TI  - [Mechanism of spontaneous rupture of hepatocellular carcinoma].
AB  - OBJECTIVE: To study the mechanism of spontaneous rupture of hepatocellular
      carcinoma (HCC). METHODS: The specimens of 30 patients with ruptured HCC and 30
      patients with non-ruptured HCC were collected. Immunofluorescence,
      immunohistochemical and flow cytometry techniques were used to detect the
      phagocytosis of macrophages and the deposition of immune complex (IC) on vascular
      wall. RESULTS: In this study, the poor function of macrophage phagocytosis was
      found in patients with ruptured HCC, which could results in the cumulating of IC
      and deposition on vascular wall. The IC, which composed of hepatitis B virus e1
      antigen (HBeAg/1), complement C1q and immunoglobulins, was found deposited in the
      elastic membrane of arteries. Likely as a result of IC deposition, vascular
      injury occurs mainly in the small arteries where the deposition of IC was
      present. As the small arteries were the blood vessels with predominant injury,
      they would likely to be the ones to split and cause hemorrhage and rupture of HCC
      during vascular load increase. CONCLUSIONS: We would conclude that the poor
      function of macrophage phagocytosis, which lead to the IC deposition and vascular
      injury may be the factors involved in the pathogenesis of ruptured HCC.

PMID- 15498315
TI  - [Clinical study of adjuvant individualized chemotherapy for hepatocellular
      carcinoma after liver transplantation].
AB  - OBJECTIVE: To investigate the effect of adjuvant individualized chemotherapy in
      prevention of tumor recurrence and improvement of patient survival after liver
      transplantation for hepatocellular carcinoma (HCC). METHODS: 21 HCC cases
      received orthotopic liver transplantation and treated with adjuvant
      individualized chemotherapy based on ATP tumor chemosensitivity assay (ex vivo)
      between April 2001 and January 2003 were retrospective reviewed, compared with 52
      cases received orthotopic liver transplantation only. The cumulative and tumor
      free survivals were compared between 2 groups. RESULTS: The 1, 2 years overall
      survival rates were 92.31%, 73.85% for the individualized chemotherapy group and
      92.06%, 63.93% for the non-chemotherapy group, the difference was not
      statistically significant. The 6, 12, 18, 24 months tumor-free survival rates
      were 90.00%, 80.00%, 80.00%, 60.00% and 67.31%, 51.92%, 40.03%, 37.81%
      respectively, the difference was statistically significant (P <0.05).
      CONCLUSIONS: This study suggests that tumor recurrence decreases and tumor-free
      survival increases by adjuvant individualized chemotherapy after liver
      transplantation for HCC. The individualized protocol based on ATP-TCA may be
      effective for patients with HCC after liver transplantation.

PMID- 15498316
TI  - [The diagnosis and treatment of hepatic artery complications in 107 cases of
      orthotopic liver transplantation].
AB  - OBJECTIVE: To investigate the diagnosis and managements of hepatic artery
      complications in orthotopic liver transplantation. METHODS: The clinical data of
      107 consecutive orthotopic liver transplantation patients was reviewed
      retrospectively to assess the risk factors and the diagnosis and treatment of the
      vascular complications. RESULTS: The incidence of the artery related
      complications in orthotopic liver transplantation was associated with the quality
      of the donor organ artery and the reconstruction way of donor-recipient artery
      intimately. The main hepatic artery related complications were hepatic artery
      thrombosis and stenosis. The incidence of the vascular complications was 6.54%,
      and the mortality rate was 85.7%. CONCLUSIONS: The main influence factors of
      vascular complications were the quality of the donor organ artery and the
      reconstruction way of donor-recipient artery. The key steps of organ salvaging
      and the patients' life saving were early diagnosis and treatment of those
      complications.

PMID- 15498317
TI  - [The possible causes of central pontine myelinolysis after liver
      transplantation].
AB  - OBJECTIVE: To sum up the clinical characteristics of patients with central
      pontine myelinolysis (CPM) after orthotopic liver transplantation (OLT) and to
      document the possible causes on CPM. METHODS: 142 patients' data with OLT between
      January 1999 to May 2003 were analyzed retrospectively. The following risk
      factors during preoperation were analyzed between patients with and without CPM:
      primary liver disease, preoperative serum sodium level, magnesium level and
      plasma osmolality, fluctuation degree of serum sodium concentration, and
      immunosuppressive drugs level etc. RESULTS: A total of 13 (9.2%) neurologic
      symptoms appeared in 142 patients post operation, including 5 cases (3.5%) with
      CPM and 8 cases (5.6%) with cerebral hemorrhage or infarct. 2 patients who
      developed CPM after OLT had hyponatremia history before operation (serum sodium
      <130 mmol/L), and the mean serum sodium level was (130.6 +/- 5.54) mmol/L. The
      serum sodium level was significantly lower in CPM than that of patients without
      neurologic complication or with cerebral hemorrhage/infarct (P <0.05). The rises
      of serum sodium perioperative 48 h after OLT in patients with CPM was
      significantly greater than that in patients with cerebral hemorrhage/infarct or
      no neurologic complication (19.5 +/- 6.54) mmol/L, (10.1 +/- 6.43) mmol/L, (4.5
      +/- 4.34) mmol/L, respectively, (P < 0.05). Plasma osmolality increased greatly
      postoperatively in patients with CPM. Hypomagnesemia was noted in all patients
      perioperatively, but there was not significant difference among groups. The
      duration of operation in CPM was longer than in others (492 +/- 190.05) min (P
      <0.05). Cyclosporin A (CsA) levels were normal in all patients, but there was
      significant difference between patients with and without neurologic complication
      (P <0.05). CONCLUSIONS: CPM may be more prevalent following liver
      transplantation. Although the diagnosis of CPM after OLT can be made by complete
      neurologic evaluation including magnetic resonance imaging (MRI) of the head, the
      mortality is still very high. The occurrence of CPM may be associated with
      hyponatremia, rapid rise of serum sodium concentration, postoperative increase of
      plasma osmolality, the duration of operation and high CsA levels.

PMID- 15498318
TI  - [Ciclosporin down-regulates interferon-gamma gene transcription via its
      inhibition of nuclear factor kappaB activity after liver transplantation].
AB  - OBJECTIVE: To investigate the relation between the activity of nuclear factor
      kappaB (NF-kappaB) and the expression of interferon (IFN)-gamma gene
      transcription with or without ciclosporin treatment after liver transplantation.
      METHODS: Orthotopic liver transplantation was performed in this study. Group I:
      syngeneic control (Wistar-to-Wistar); Group II: acute rejection (SD-to-Wistar);
      Group III: acute rejection treated with ciclosporin by intramuscular route (SD-to
      Wistar + ciclosporin). Electrophoretic mobility shift assay and reverse
      transcriptase polymerase chain reaction were used to analyze NF-kappaB activity
      of splenocytes and IFN-gamma gene transcription expression of grafted liver with
      or without ciclosporin treatment after liver transplantation. Histopathological
      examination was also used in this study. RESULTS: Low NF-kappaB activity was only
      detected at day 5 and day 7 in Wistar-to-Wistar group after transplantation,
      meanwhile low IFN-gamma mRNA expression was detected at any time in this group.
      In contrast, high NF-kappaB activity was detected in SD-to-Wistar group and high
      level IFN-gammamRNA expression was detected at all time points in this group. The
      activity of NF-kappaB and IFN-gammamRNA expression were significantly inhibited
      in SD-to-Wistar + ciclosporin group which was significantly lower than that of SD
      to-Wistar group (P < 0.001). A good correlation was found between activity of NF
      kappaB and IFN-gamma mRNA expression in this study (r=0.815, P <0.01).
      CONCLUSIONS: The change of expression IFN-gamma mRNA is at least partially due to
      the activity change of NF-kappaB after orthotopic liver transplantation. CsA down
      regulates NF-kappaB activity and further inhibit IFN-gamma gene transcription.

PMID- 15498319
TI  - [Total cyst excision with ultrasonic scalpel under the laparoscope for
      choledochal cyst].
AB  - OBJECTIVE: To discuss the technique and its advantage on application of
      ultrasonic scalpel in laproscopic cyst excision with Roux-en-Y hepatoenterostomy.
      METHODS: Forty-five cases were undergone laparoscopic cyst excision with Roux-en
      Y hepatoenterostomy by ultrasonic scalpel. After intraoperative cholangiogram,
      the gallbladder and the dilated bile duct were completely excised by ultrasonic
      scalpel. Roux-en-Y hepatoenterostomy was performed extracorporeally through
      umbilical incision, then an end-to-side anastomosis was carried out
      intracorporeally. RESULTS: All 45 cases were completely accomplished under
      laparoscope combined with ultrasonic scalpel. Median duration of operation was
      4.2 h (3.5-6.0 h). Intraoperative bleeding was between 10-50 ml (median 15 ml).
      No complication were found during operation. All children were discharged in 3-9
      d (median 5.5 d) after operation. Thirty-eight cases were followed up 1-18
      months. No stenosis or ileus occurred. Liver functions were in normal level.
      CONCLUSIONS: Total cyst excision with Roux-en-Y hepatoenterostomy by ultrasonic
      scalpel under the laparoscope was effective and safe for choledochal cyst. The
      most excellence was that clearly viewing during operation, less bleeding and
      injury, free of pain postoperation, microincision and scar.

PMID- 15498320
TI  - [Detection of alpha-fetoproteins mRNA and melanoma antigen-1 mRNA in peripheral
      blood of patients with hepatocellular carcinoma and its clinical significance].
AB  - OBJECTIVE: To explore the feasibility of alpha-fetoproteins (alpha-FP) mRNA and
      melanoma antigen-1 (MAGE-1) mRNA as 2 markers of micrometastasis in
      hepatocellular carcinoma (HCC) patients' peripheral blood. METHODS: Subjects were
      divided into five groups: patients with HCC (n=65); patients with hepatitisB and
      liver cirrhosis (n=22); patients with metastatic liver cancer (n=12); patients
      with hepatic hemangioma (n=12); and healthy volunteers (n=20). alpha-FP mRNA and
      MAGE-1 mRNA in peripheral blood were tested by nested reverse transcription
      polymerase chain reaction (RT-PCR). RESULTS: MAGE-1 mRNA and alpha-FP mRNA were
      detected in 27 (42%) and 35 (54%) of 65 HCC patients respectively, while 42 (65%)
      HCC patients were positive for at least 1 marker. The frequency of alpha-FP mRNA
      and MAGE-1 mRNA positivity strongly correlated with portal thrombosis,
      intrahepatic metastatic nodules, tumor diameter and TNM stage (P <0.05). With
      regard to controls, 4 of 12 (33%) samples from patients with metastatic liver
      cancer showed MAGE-1 mRNA in their peripheral blood, but groups of hepatitis and
      cirrhosis, hepatic hemangioma, healthy volunteers did not. And 3 of 22 samples
      (14%) from group hepatitis and cirrhosis showed alpha-FP mRNA, but none of
      samples from other control group showed alpha-FP mRNA. CONCLUSIONS: Nested RT-PCR
      is a sensitive and reliable method for detecting circulating HCC cells. Two
      marker RT-PCR assay with a liver-specific alpha-FP marker in combination with a
      cancer-specific MAGE-1 marker may be a promising tool for detecting
      micrometastases with better sensitivity and specificity than one marker RT-PCR.

PMID- 15498321
TI  - [Study on the interface of human hepatocyte L-02 polypropylene:simple culture
      method of human hepatocyte with spheroidal aggregate culture].
AB  - OBJECTIVE: To found new interface of human hepatocyte/poly propylene with good
      cytocompatibility for made polypropylene hollow fibers bioreactor of
      bioartificial liver in future. METHODS: Using the macromolecular hydroperoxide
      groups on the polypropylene membrane surface as initiators, acrylamides were
      polymerized on the polypropylene membranes, under induction by both UV
      irradiation and Fe2+ reduction. Growth characteristics of human hepatocyte L-02
      were detected when it was cultured on polystyrene, polypropylene and modified
      polypropylene membrane surface. RESULTS: Water contact angle measurement of the
      polypropylene and the modified polypropylene membranes decreased from (72 +/- 5)
      degrees to (30 +/- 4) degrees , which indicated that the hydrophilicity of the
      membrane was improved obviously after the grafting modification. Human hepatocyte
      L-02 could not adhere and spread on modified polypropylene membrane surface, and
      grown in spheroidal aggregate with higher density and higher proliferation ratio
      measured by MTT method. CONCLUSIONS: Acrylamide polymerized on the polypropylene
      membranes is a good method which not only improved human hepatocytes
      cytocompatibility but also found a new simple culture method with spheroidal
      aggregate culture of human hepatocyte.

PMID- 15498322
TI  - [Expression and significance of caspase-3 gene in apoptotic muscle cells 103Pd
      radioactive stent bile duct in dogs].
AB  - OBJECTIVE: To discuss the expression and significance of caspase-3 gene in the
      apoptotic muscle cells in gamma-radiation-induced muscle cell lines. METHODS: The
      caspase-3 mRNA in the control and gamma-radiation induced apoptotic muscle cells
      was analysed by RT-PCR. RESULTS: The expression of caspase-3 gene transcript was
      higher in 103Pd radioactive stent dog bile duct than in general stent dog bile
      duct, and apoptotic muscle cells were higher in 103Pd radioactive stent dog bile
      duct than in general stent dog bile duct. CONCLUSIONS: The high level expression
      of caspase-3 gene may help to understand the muscle cells sensitivity to gamma
      radiation apoptosis. 103Pd radioactive stent may increase the expression of
      caspase-3 gene in dog bile duct and prevent the billiary narrow when dog bile
      duct was injured by balloon.

PMID- 15498332
TI  - [Improve whole level of the sequence treatment in cleft lip and palate].

PMID- 15498334
TI  - [Perioperative risk factors evaluation of cleft palate repair in Pierre Robin
      sequence at early age].
AB  - OBJECTIVE: To evaluate the perioperative risk factors of the cleft palate repair
      in Pierre Robin sequence patients at early age and to investigate how to control
      the risk factors. METHODS: Six consecutive patients with Pierre Robin sequence
      underwent primary repair of cleft palate in Department of Oral Maxillofacial
      Surgery, Peking University School of Stomatology from June 2001 to February 2004.
      The patients underwent von Longenbeck operation by the same perioperative
      observation of serum oxygen saturation were obtained for these patients. patients
      included 4 males and 2 females with age of 9 months to 5 surgeon. Pre- and post
      operative polysomnographic studies and years. RESULTS: All the patients suffered
      various degree of hypoxaemia during the period of intubation. There was only one
      patient who had hypoxaemia within the first 2 hours during postanaesthetic
      recovery period. No obvious difference was found in apnea and hypopnea index
      (AHI) among the patients before and after operation. CONCLUSIONS: Severe
      hypoxaemia may happen in perioperative period when the patients with PRS
      underwent cleft palate repair. Most patients with PRS could undergo cleft palate
      repair safely performed by experienced surgeon at early age under comprehensive
      consideration and careful control of the risk factors.

PMID- 15498335
TI  - [Key points of theory and technique in unilateral cleft lip repair].

PMID- 15498336
TI  - [Surgical correction of secondary deformities with lip and palate cleft].

PMID- 15498337
TI  - [The Fourth National Cleft Lip and Palate Academic Conference summary].

PMID- 15498338
TI  - [Preliminary proposal of the severity score system for maxillofacial injuries].
AB  - OBJECTIVE: A new injury severity score system was proposed in this study to
      evaluate maxillofacial injuries. METHODS: Based on AIS-90, all clinical samples
      were given diagnosis. Their month opening limitation, malocclusion and facial
      deformity were recorded as indices in scoring system. Severity injury scores for
      different groups and types were statistically. analyzed. RESULTS: It was
      demonstrated that there was a significant difference in scores between injuries
      of soft tissue and bone tissue and between different fracture groups.
      CONCLUSIONS: The proposed scoring was system useful to predict the cost of
      medical care and the days of in-patient, reliable, sensitive and specific in
      evaluation the maxillofacial injury severity.

PMID- 15498339
TI  - [Effect of salvage surgery for patients with recurrent oral squamous cell
      carcinoma].
AB  - OBJECTIVE: To examine the benefit of restaging recurrent oral squamous cell
      carcinoma (R-OSCC) and the effect on salvage surgery. METHODS: An analysis was
      performed on 30 patients with local only first failure (n = 13) or loca-regional
      only first failure (n = 9) or first recurrence in the neck (n = 8) after surgery
      and/or radiation treatment given for oral squamous cell carcinoma. All the 30
      patients were restaged and treated with salvage surgery. RESULTS: The overall
      survival time and disease-free survival time of patients with early staged R-OSCC
      was longer than that of patients with advanced staged R-OSCC. The 1-year survival
      and 1-year disease-free survival rates for early staged R-OSCC is also higher
      than that of advanced staged R-OSCC. CONCLUSIONS: The re-stage of the recurrent
      tumor is significantly correlated with survival. The salvage surgery is an
      effective measure in patients with recurrent oral squamous cell carcinoma,
      especially in early staged patients of R-OSCC.

PMID- 15498340
TI  - [Antimetastatic effects of genistein on salivary adenoid cystic carcinoma in
      vivo].
AB  - OBJECTIVE: To study the antimetastatic effects of genistein on salivary adenoid
      cystic carcinoma (ACC-M) in vivo. METHODS: ACC-M cells were exposed to genistein
      for 3 days. The treated cells and control cells were then injected into the tail
      vein of 20 nude mice, which were randomized into 2 groups. The mice were
      sacrificed at the sixth week after implantation. The lung metastasis rates and
      the number of metastases were detected. Apoptosis index (AI), the expression of
      VEGF and MMP-9 of the lung metastases were also observed. RESULTS: Compared to
      the control groups, the number of metastases was significantly reduced in
      genistein treated group (P < 0.05). The AI of ACC-M cells was higher in the
      treated group than in the control group (P < 0.05). The level of VEGF and MMP-9
      expression were decreased in the treated groups (P < 0.05). CONCLUSIONS:
      Genistein has a moderate inhibitory effect on metastasis of ACC. Inducing
      apoptosis, inhibiting the expression of VEGF and MMP-9 are the mechanisms of
      antimetastatic effects of genistein on ACC-M in nude mice.

PMID- 15498341
TI  - [Telomerase SiRNA inhibits KB cell growth in human oral squamous cell carcinoma].
AB  - OBJECTIVE: To test the telomerase SiRNA on telomerase mRNA and on KB cell growth
      of oral squamous cell carcinoma. METHODS: We synthesized 21-nucleotide SiRNA
      duplexes with symmetric 2-nucleotide 3' overhangs corresponding to the target
      sequence (2 657 approximately 2 675 nucleotide downstream of the start codon) of
      telomerase mRNA. Telomerase activity, cell proliferation, cell cycle and
      apoptosis were measured after transfection. RESULTS: Twenty one-nucleotide small
      interfering RNA (SiRNA) duplexes specifically suppressed expression of endogenous
      telomerase mRNA in human oral squamous carcinoma KB cells. This inhibitory effect
      lasted only for about 48 h after transfection. Telomerase activity reduction
      corresponded to the mRNA suppression. Cell proliferation decreased by 30% at 48 h
      after transfection and lasted for 120 h after treatment. This inhibitory effect
      resulted from the block of G(1) to S transition. Apoptosis was not involved in
      this process. CONCLUSIONS: SiRNA is a powerful tool for studying gene function
      and can be used as gene-specific therapeutics.

PMID- 15498342
TI  - [Management of intracanal separated instruments with the microsonic technique and
      its clinical outcome].
AB  - OBJECTIVE: To evaluate the clinical effect of microsonic technique on removal of
      intracanal separated instruments. METHODS: Forty-four teeth with 47 intracanal
      separated instruments, which could not be successfully managed by conventional
      methods, were endodontically treated with ultrasonic instruments under dental
      operating microscope. The success rate was calculated and the cases were reviewed
      5 to 19 months after retreatment. RESULTS: Thirty-four (34/47) separated
      instruments in 33 (33/44) teeth were completely removed with a success rate of
      75%. Thirteen separated instruments in 11 teeth, however, could not be eliminated
      from the canals. Root canal perforation or vertical fracture was not found. None
      of these teeth showed periapical deterioration in the follow-up. CONCLUSIONS: The
      combined use of dental operating microscope and ultrasonic instruments in
      endodontic treatment enriched the way of managing complicated cases of intracanal
      separated instruments.

PMID- 15498343
TI  - [Preliminary study on gene related to acid tolerance of Streptococcus mutans].
AB  - OBJECTIVE: To construct an acid-sensitive mutant of Streptococcus mutans (S.
      mutans) by transposon mutagenesis and to find a new gene related to the acid
      tolerance of S. mutans. METHODS: The transposon Tn917 was delivered into S.
      mutans UA159 by the temperature-sensitive plasmid pTV1-OK bearing Tn917 and
      transposition of Tn917 was induced after incubation at non-permissive temperature
      (42 degrees C). Transposants harboring Tn917 in the chromosome were screened for
      the selection of mutant that had diminished growth at low pH. Southern analysis
      was performed with EcoRI (no cut within Tn917) digests of S. mutans UA159 and the
      selected aid-sensitive mutant, with DIG-labeled probe of 4.3 kb KpnI fragment of
      pTV1-OK containing Tn917. Genetic backcross experiment was performed by
      transforming the genome of the mutant to another S. mutans strain MT8148 to
      determine the linkage of Tn917 insertion to the change of phenotype (acid
      sensitivity). Comparison of the abilities to grow at low pH, the glycolytic pH
      drop and killing pH values were done between the acid-sensitive mutant and the
      parent strain. The asymmetric PCR method was used to obtain the fragment flanking
      Tn917 and the PCR products were cloned to pMD18-T vector for sequencing. RESULTS:
      One mutant that showed no growth at pH 5.0 was isolated from 2 316 transposants
      and was named as b23. Southern analysis and genetic backcross experiment
      confirmed the linkage between single Tn917 insertion into the chromosome and the
      phenotypic change (acid sensitive). b23 was less acid tolerant than UA159 in that
      it showed poorer growth at low pH and higher glycolytic pH minimum and higher
      killing pH. BLAST results indicated that Tn917 inserted into the genome of S.
      mutans UA159 at the site of 996 123 bp. CONCLUSION: An acid-sensitive mutant of
      S. mutans was successfully constructed and a new gene that is responsible for the
      acid tolerance in S. mutans UA159 was revealed.

PMID- 15498344
TI  - [Bone morphogenetic protein-2-induced alpha 2 (I) collagen expression in
      odontoblastic MDPC-23 cells mediated by Smad proteins].
AB  - OBJECTIVE: To characterize the role of Smads proteins in alpha 2 (I) collagen
      (COL1A2) gene expression induced by bone morphogenetic protein-2 (BMP-2) in
      odontoblast cell line MDPC-23. METHODS: Endogenous Smad protein expression was
      determined by immunocytochemistry. Smads function and their role in COL1A2 gene
      expression were investigated in cotransfection experiments using promoter
      luciferase reporter gene construct. RESULTS: MDPC-23 cells expressed Smad1, Smad5
      and Smad6. BMP-2 promoted the activation of COL1A2 promoter reporter construct.
      Transient overexpression of Smad1 or Smad5 was enhanced, while overexpression of
      Smad6 inhibited BMP-2-induced COL1A2 promoter activity. BMP-2 inducibility could
      be blocked by overexpression of Smad1 or Smad5 dominant negative mutant.
      CONCLUSIONS: Smad signaling is functioning and appears to be involved in BMP-2
      induced COL1A2 collagen transcription in MDPC-23. Smad signaling may play an
      important role in odontoblast differentiation and dentin extracellular matrix
      formation mediated by BMP-2.

PMID- 15498346
TI  - [Association of mandibular angle size with cortical thickness and residual ridge
      height of the edentulous mandible].
AB  - OBJECTIVE: To evaluate the mandible angle and to investigate the relationship of
      angle size to gender, age-group, cortical thickness at the mandibular angle
      (CTMA), height of mandibular residual body, and edentulous period in the elderly
      edentulous subjects. METHODS: A total of 356 panoramic radiographs of three
      groups of subjects were evaluated: the young dentate group, 131 subjects (mean
      age: 27); the older dentate group, 97 (mean age: 64); and the elderly edentulous
      group, 128 (ages 76, 81, or 86). Mandibular angle size, CTMA, and height of
      mandibular residual body were measured from panoramic radiographs. A structured
      questionnaire was used to determine the history of edentulousness. RESULTS:
      Difference in angle size was found between dentate men and women (P < 0.05, P <
      0.001), but not between the elderly edentulous men and elderly women. The elderly
      edentulous subjects had larger mandibular angles than did older dentate subjects
      (P < 0.001). The angle size was negatively related to CTMA only among 76-year-old
      edentulous women (P < 0.01) and negatively associated with average height of the
      mandibular residual body in the edentulous men and women (P < 0.01). No
      association existed between angle size and duration of edentulousness.
      CONCLUSIONS: Elderly edentulous subjects have large mandibular angles and the
      angle size is correlated with low-height of the mandibular residual body, which
      suggests that masticatory function of natural dentition and complete denture may
      influence change of the mandibular angle. The significant relationship of
      mandibular angle size to CTMA probably indicates the effect of systemic factors
      on change in the mandibular angle.

PMID- 15498347
TI  - [A preliminary study on the color effect of IPS Empress all-ceramic veneers].
AB  - OBJECTIVE: To evaluate the opaquing capacity, color compatibility and stability
      of IPS Empress all-ceramic veneers. METHODS: A total of 86 IPS Empress all
      ceramic veneers were made for 18 patients. The patients were divided into three
      groups: Group A was tetracycline teeth, 64 veneers for 5 patients; Group B was
      non-tetracycline teeth, 22 veneers for 13 patients; Group C was 22 natural vital
      teeth with normal color as control group. Before and after veneers were inserted,
      ShadeEye NCC was employed to obtain L * a * b * values of each tooth. The values
      of cemented veneers used as the baseline, the L * a * b * values of each veneer
      were measured half a year, 1 year, and 2 years after restoration respectively.
      All L * a * b * values at different evaluation times were analyzed by SPSS 10.0.
      RESULTS: Before and after veneers were restored, the L * a * b * values of both
      Group A and Group B were significantly different, the color difference being 5.01
      and 4.15 respectively. The color difference between Group A and selected shade
      guides was 2.45. Compared with the baseline value, the L * value of Group A
      significantly decreased 2 years after restoration, but the DeltaE of different
      evaluation times was not significantly different. The color difference between
      Group B and Group C was 0.22 and there was no significant color difference after
      restoration. CONCLUSIONS: IPS Empress all-ceramic veneers have excellent opaquing
      capacity, color compatibility and stability to non-tetracycline teeth. To
      tetracycline teeth IPS Empress all-ceramic veneers have a certain opaquing
      capacity, but they cannot completely match with shade guides; the L * value is
      significantly different after restoration and further studies are needed to
      evaluate its color effect.

PMID- 15498348
TI  - [Combined orthodontic-periodontal treatment on periodontal patients with anterior
      displaced incisors].
AB  - OBJECTIVE: Combined orthodontic-periodontal treatment with supracrestal
      fiberotomy was undergone on the periodontal patients with anterior displacement
      of incisors. Evaluate of the changes before and after treatment. METHODS:
      Periodontal indices, periapical x-ray analysis, and model analysis were used for
      investigating the changes of alveolar bone height and periodontal health by
      orthodontic treatment following supracrestal fiberotomy of anterior displaced
      incisors on periodontal patients. RESULTS: Alveolar bone height was increase by
      1.2 mm in fiberotomy patients. The overjet was reduced from 7.0 mm to 2.0 mm,
      while the overbite was decreased from 4.0 mm to 2.0 mm, and the periodontal
      health maintained as well. CONCLUSION: Combined orthodontic periodontal treatment
      with supracrestal fiberotomy could correct the malpositioned teeth, and improve
      the periodontium conditions and gain the crest bone.

PMID- 15498349
TI  - [Orthodontic extrusion of crown-root fractured teeth and teeth with root caries-
      report of 5 cases].
AB  - OBJECTIVE: To discuss orthodontic extrusion of crown-root fractured teeth before
      restoration. METHODS: 3 cases with fractured teeth and 2 cases with root caries
      were performed canal therapy. RESULTS: Orthodontic extrusion of the root was
      carried out before restoration. All cases were satisfactory after treatment.
      CONCLUSIONS: Orthodontic extrusion of remaining root before restoration not only
      can maintain the remaining root but also obtain functional and esthetic results.

PMID- 15498350
TI  - [Expression of pRb and E2F-1 and telomerase activity in ameloblastoma].
AB  - OBJECTIVE: To investigate the expression of pRb and E2F-1, and the association
      between their expression and the activity of telomerase (hTERT) or cyclin E in
      human ameloblastoma (AB), and to explore the clinical biological characteristics
      of AB. METHODS: The expressions of pRb, E2F-1, cyclin E and hTERT mRNA in human
      AB were detected by in situ hybridization or immunohistochemistry (SP method).
      RESULTS: The positive expression ratio of pRb in the cell nucleus of AB was 20.4%
      (11/54). The positive ratio of E2F-1, cyclin E and hTERT mRNA was 92.6% (50/54),
      66.7% (36/54) and 94.4% (51/54), respectively. With AB recurrence and malignant
      transformation, the expression of hTERT, E2F-1, cyclin E was up-regulated. hTERT
      and cyclin E or E2F-1 mRNA had high positive relation (Spearsman'r(s) = 1.000, P
      = 0.0001). CONCLUSIONS: The regulatory pathway of Rb/E2F-1 is associated with the
      cell proliferation and in differentiation of AB. The activity or release of
      telomerase may be related to the lower expression of Rb and higher expression of
      E2F-1, and is up-regulated in G(1) late phase by cyclin E.

PMID- 15498351
TI  - [Immunohistochemical study of benign lymphoadenosis of oral mucosa].
AB  - OBJECTIVE: To study the expression of Ki-67 and the changes of MVD and apoptosis
      in benign lymphoadenosis of oral mucosa (BLOM). METHODS: The expression of Ki-67,
      CD34 and apoptosis were evaluated by SP immunohistochemical staining in 15 BLOM,
      9 BLOM with dysplasia, 15 oral squamous cell carcinoma (OSCC). RESULTS: The
      expression of Ki-67 in BOLM with dysplasia and OSCC was significantly higher than
      that of BLOM without dysplasia and normal oral mucosa (P < 0.05). The MVD in all
      BLOM and OSCC was significantly higher than that in normal mucosa (P < 0.05).
      Apoptosis in BLOM was higher than in normal mucosa and OSCC (P < 0.05).
      CONCLUSIONS: The expression of Ki-67 and MVD in BLOM with dysplasia were between
      normal oral mucosa and oral carcinoma. The occurrence of apoptosis in BLOM was
      significantly higher than in normal oral mucosa. The results suggest that BLOM
      had the potentiality of malignant transformation.

PMID- 15498352
TI  - [Enamelin transcriptional expression in developing postnatal rat tooth germ].
AB  - OBJECTIVE: To observe the transcriptional expression of enamelin in developing
      postnatal rat first mandibular molar germs, for further studies of functions of
      enamelin in enamel development and mineralization. METHODS: Tissue slices of
      first mandibular molar germ of rat 1, 3, 7, 10, 14 days after birth were
      prepared. The enamelin mRNA expression was identified by in situ hybridization.
      RESULTS: Enamelin mRNA was observed in both ameloblast and odontoblast in 1-10
      day old rat postnatal first mandibular molar germs. Enamelin mRNA appeared very
      weakly at 1st day, and increased through 3rd day, reached the maximum at 7th day,
      and reduced at 10th day and became negative at 14th day postnatally; while the
      expression of enamelin mRNA in odontoblast maintained lower from 1st to 10th day
      and negative at 14th day postnatally. CONCLUSION: Enamelin gene transcriptional
      expression lasts from preameloblast to maturation ameloblast, which suggests that
      enamelin may participate in the development of enamel and mantle dentin.

PMID- 15498354
TI  - [The expression of PPTA and c-fos mRNA in dog caudal spinal trigeminal nucleus
      induced by traumatic occlusion].
AB  - OBJECTIVE: PPTA and c-fos mRNA expression were detected in dog caudalis
      subnucleus of trigeminal spinal tract nucleus (VC) induced by trauma occlusion in
      order to investigate orofacial pain mechanism. METHODS: The occlusal surface of
      the first and second maxillary right molars in 15 dogs were unilaterally raised
      1.5 mm with casting Ni-Cr inlay which were fixed in Class I hole. On days 3, 7,
      14, 30 and 60 after teeth operation, the VC of right and left sides were removed.
      PPTA and c-fos mRNAs were detected in experimental and control groups with
      reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: (1) The basal
      levels of PPTA and c-fos mRNAs were extremely low and poorly detectable in VC in
      control animals. (2) The expression of PPTA mRNA in VC of traumatic side was up
      regulated from 3 days after inlay was fixed in molar and reached peak level
      during 14 to 30 days and then down-regulated gradually and no significant
      difference was noted between 60 days group and control group. (3) c-fos mRNA
      expression was more intense during 3 to 7 days compared with the control group
      but undetectable in the other experimental period. (4) Both PPTA and c-fos mRNAs
      expression in VC of trauma occlusal side were more intense than that in the
      contralateral side. CONCLUSIONS: The present results show that both PPTA and c
      fos mRNA expression are elevated in dog's VC induced by traumatic occlusion. The
      primary afferent terminal of orofacial area is sensitized, which suggest one kind
      of mechanism of orofacial pain in the condition of traumatic occlusion.

PMID- 15498355
TI  - [Expression of PN3 and NaN in trigeminal ganglion during occlusal trauma in rat].
AB  - OBJECTIVE: To investigate changes of two sodium channels, PN(3) and NaN, during
      orofacial pain by occlusal trauma in rat. METHODS: Expressions of PN(3) mRNA and
      NaN mRNA in trigeminal ganglion were tested during various periods of persistent
      occlusal trauma with reverse transcription-polymerase chain reaction (RT-PCR).
      RESULTS: In groups, including control, occlusal trauma groups, PN(3) mRNA and NaN
      mRNA were all expressed in trigeminal ganglion neurons. In the control group,
      there were similar density values bilaterally. In the occlusal trauma group, the
      density values in gel electrophoresis of PN(3) mRNA and NaN mRNA on the
      intervention side were slightly greater than those on the control side.
      CONCLUSIONS: The stimulation of occlusal trauma upregulates expressions of PN(3)
      mRNA and NaN mRNA, which suggests the signal occurring and conduction of chronic
      pain by occlusal trauma have the same molecular mechanism of sodium channel as
      inflammatory pain.

PMID- 15498356
TI  - [A study of 108 cases on facial nerve contralateral innervation after facial
      nerve injury].
AB  - OBJECTIVE: To investigate the facial nerve contralateral innervation of patients
      with facial nerve injury. METHODS: Electroneuronography (ENoG) of 22 university
      student volunteers (US) without any injury and systemic diseases and 108 patients
      with facial nerve injury were measured. The patients were divided into three
      groups: iatrogenic, traumatic, and Bell's palsy groups. When stimulating the
      facial nerve at the site below the lobule and behind the ramus, ENoGs of each
      branch of the facial nerve on ipsilateral and contralateral sides were recorded.
      A total of 76 branch I, 81 branch II, 88 branch III, and 66 branch IV were
      measured. RESULTS: (1) There were no significant differences among three patient
      groups (P > 0.05). (2) The ratios of contralateral innervation of the branch I
      and II of the patients were significantly. greater than those of the US group (P
      < 0.001). (3) The ratio of contralateral innervation of the branch I was greater
      than that of the branch II in the patients (P < 0.001). CONCLUSION: The
      contralateral innervation of the facial nerve increases after facial nerve
      injured.

PMID- 15498357
TI  - [Quality control in private dental office].

PMID- 15498358
TI  - [Guide for The Examination of National Certified Dentist Preparation: A review
      guideline and strategy on prosthodontics for the candidates National certificated
      dentist qualification test].

PMID- 15498359
TI  - [Temporomandibular joint surgery].

PMID- 15498360
TI  - [Discussion of the mental state problem in children with cleft lip and palate and
      their parents].

PMID- 15498361
TI  - [Non-glucocorticoid therapy for pemphigus].

PMID- 15498362
TI  - Improvement of cardiac function after transplantation of autologous bone marrow
      mesenchymal stem cells in patients with acute myocardial infarction.
AB  - BACKGROUND: The infarct size determines the long-term prognosis of patients with
      acute myocardial infarction (AMI). There is a growing interest in repairing scar
      area by transplanting bone marrow stem cells. However, effectiveness of
      intracoronary injection of bone marrow mesenchymal stem cells (BMSCs) in patients
      with AMI still remains unclear. METHODS: Sixty-nine patients with AMI after
      percutaneous coronary intervention (PCI) were randomly divided into intracoronary
      injection of BMSCs (n = 34) and saline (control group, n = 35) groups. Serial
      single positron emission computer tomography (SPECT), cardiac echo and cardiac
      electromechanical mapping were done at the designed time intervals until six
      months after transplantation of BMSCs or injection of saline. RESULTS: The
      proportion with functional defect decreased significantly in the BMSCs patients
      after three months [(13 +/- 5)%] compared with that pre-transplantation [(32 +/-
      11)%] and the control group [(28 +/- 10)%] at three month follow-up (P < 0.05,
      respectively). Wall movement velocity over the infracted region increased
      significantly in the BMSCs group [(4.2 +/- 2.5) cm/s vs (2.2 +/- 1.3) cm/s, P <
      0.05], but not in the control group [(2.2 +/- 1.5) cm/s vs (2.7 +/- 1.7) cm/s, P
      > 0.05]. Left ventricular ejection fraction (LVEF) three months after
      transplantation in BMSCs group increased significantly compared with that pre
      implantation and with that of the control group at three months post-injection
      [(67 +/- 11)% vs (49 +/- 9)% and (53 +/- 8)%, P < 0.05 respectively]. SPECT scan
      results showed that perfusion defect was improved significantly in BMSCs group at
      three-month follow-up compared with that in the control group [(134 +/- 66) cm(2)
      vs (185 +/- 87) cm(2), P < 0.01]. At the same time, left ventricular end
      diastolic volume [(136 +/- 31) ml vs (162 +/- 27) ml, P < 0.05] and end-systolic
      volume [(63 +/- 20) ml vs (88 +/- 19) ml, P < 0.05] decreased synchronously. The
      ratio of end-systolic pressure to end-systolic volume [Psyst/ESV, (2.84 +/- 1.30)
      mmHg/ml vs (1.72 +/- 1.23) mmHg/ml, P < 0.05] increased significantly. Cardiac
      electromechanical mapping demonstrated significant improvement at three months
      after implantation of BMSCs compared with that pre-injection in both cardiac
      mechanical capability as left line local shorting [LLS, (11.29 +/- 1.64)% vs
      (7.32 +/- 1.86)%, P < 0.05] and electrical property as left ventricular
      endocardial unipolar voltage [UV, (10.38 +/- 1.12) mV vs (7.61 +/- 1.09) mV, P <
      0.01]; perfusion defect decreased from (36.2 +/- 6.2)% to (20.3 +/- 5.31)% (P <
      0.01). Twenty-four-hour electrocardiographic monitoring demonstrated no
      arrhythmias occurred at three-months follow-up. CONCLUSIONS: The transplantation
      of BMSCs might improve the cardiac function and it is safe and feasible with no
      deaths or malignant arrhythmias.

PMID- 15498363
TI  - Relationship between HLA-DQA1 polymorphism and genetic susceptibility to
      idiopathic dilated cardiomyopathy.
AB  - BACKGROUND: Autoimmune mechanisms are likely to participate in the pathogenesis
      of subgroup of idiopathic dilated cardiomyopathy (IDC), and components of the
      major histocompatibility complex may serve as markers for the propensity to
      develop immune-mediated myocardial damage. Human leukocyte antigen (HLA) class II
      genes, especially highly polymorphic HLA-DQ genes, play an important role in the
      activation of immune responses, and thus control the predisposition for or
      protect from IDC. This study was conducted to investigate the HLA-DQA1 allele
      polymorphisms in IDC patients and to explore the underlying immunological
      mechanism and the hereditary susceptibility to IDC. METHODS: The polymerase chain
      reaction sequence-specific primers (PCR-SSP) technique was used to analyze the
      polymorphisms in the second exon of DQA1 in three groups: 72 IDC patients
      diagnosed according to the criteria of World Health Organization (IDC group); 100
      end-stage heart failure patients suffering from a disease of known etiology (HF
      group); and 100 healthy subjects enrolled for the study during a routine health
      survey (control group). Patients in the IDC group were stratified according to
      ejection fraction (EF). Those with EF values were higher than 35% were placed
      into subgroup 1; subgroup 2 included patients with an EF value of 15% - 35%; and
      subgroup 3 consisted of those whose EF values less than 15%. RESULTS: The
      frequency of HLA-DQA1 *0501 alleles was significantly higher in the IDC group
      (0.39) than that in the HF group (0.12) and the control group (0.09) (both P <
      0.05). Further analysis of the three IDC subgroups showed a higher frequency of
      DQA1 *0501 among patients with lower EF values (both P < 0.05, compared with
      subgroups 1 and 2). The frequency of DQA1 *0201 was higher in the control group
      than that in the IDC group (P < 0.05). CONCLUSIONS: The HLA-DQA1 *0501 allele
      confers susceptibility to IDC, while the DQA1 *0201 allele confers protection
      against it, which indicates that genetic background involved in IDC and heart
      failure is different. HLA-DQA1 genes are involved in the regulation of specific
      immune responses by auto- or foreign anti-myocardium antibody.

PMID- 15498364
TI  - Effects of hypoxia on coronary flow reserve as determined by myocardial contrast
      echocardiography in swine.
AB  - BACKGROUND: Time-intensity curves derived from microbubble destruction/refilling
      sequences and recorded using myocardial contrast echocardiography (MCE) can
      provide parameters that correlate with coronary blood flow. The response of these
      parameters to adenosine vasodilatation correlates with coronary flow reserve
      (CFR) measured by fluorescent microsphere techniques (FMT). Currently, no data
      exist regarding the effect of physiological variables, such as hypoxia, on the
      determination of CFR by MCE. The purpose of this study was to define the effects
      of decreases in blood partial pressure of oxygen (PO2) on CFR as measured by MCE.
      METHODS: Studies were performed in 9 closed chest swine. Low-energy, real-time
      MCE was performed with commercial instruments in short axis view at papillary
      muscle level while infusing BR1 at 30 ml/h. High-energy ultrasound bursts
      (referred to as FLASH frames) destroyed the bubbles every 15 cardiac cycles, and
      resultant time-intensity curves derived from these sequences were fitted to the
      exponential function y = A [1-e(-bt)] + c, from which the rate of signal rise (b)
      was obtained. CFR was calculated as the ratio of b values after adenosine
      infusion to baseline and was obtained during the control period and after
      decreasing blood PO2 by giving nitrogen via a respirator to create artificial
      hypoxic conditions. CFR was independently determined by FMT. RESULTS: Nitrogen
      led to significant decreases in mean PO2, from (120.6 +/- 18.9) mmHg to (51.8 +/-
      15.9) mmHg (P < 0.01). Adenosine produced a similar increase in CFR (2.5 fold vs
      3.1 fold) as assessed by MCE and FMT during the control period. The decrease in
      PO2 post nitrogen resulted in a slight increase in values at rest: 0.46 +/- 0.15
      to 0.53 +/- 0.18 for b and (1.39 +/- 0.66) ml x min(-1) x g(-1) to (1.72 +/-
      0.30) ml x min(-1) x g(-1) for myocardial blood flow (MBF) (both P < 0.05). In
      addition, values decreased in response to adenosine using both techniques: 1.05
      +/- 0.35 to 0.82 +/- 0.27 for b and (4.30 +/- 3.16) ml x min(-1) x g(-1) to (3.93
      +/- 1.27) ml x min(-1) x g(-1) for MBF (both P < 0.05). Thus, CFR was markedly
      reduced under hypoxic conditions, to 1.4 by MCE (P < 0.05 compared with the
      baseline), and to 2.5 by FMT (P > 0.05 compared with the baseline). CONCLUSIONS:
      CFR values diminish under hypoxic conditions according to both MCE and FMT. The
      reductions in CFR involve both an increase in resting values and a decrease in
      post adenosine measurements, as determined by both techniques. The reduction in
      CFR under hypoxia is slightly greater using MCE than using FMT. Physiological
      variables, such as hypoxia, must be taken into consideration when assessing CFR
      by MCE.

PMID- 15498365
TI  - Pharmacokinetics of rapamycin-eluting stents in miniswine coronary model.
AB  - BACKGROUND: The results of clinical trials of rapamycin-eluting stents reduce
      restenosis have been quite promising. The main purpose of this study was to
      characterize the in vivo pharmacokinetics of high dose rapamycin (Rapa)-eluting
      stents in a miniswine coronary model. METHODS: Ten miniswines underwent placement
      of 18 high dose Rapa-eluting stents in the left anterior descending and right
      coronary arteries. At the planned times of the 1.5th, 12th, 24th hour, 3th, 7th
      and 28th day, the animals (n = 1, 1, 2, 2, 2, and 2, respectively) were
      euthanized after completion of coronary angiography. Blood samples were obtained
      at 0, 10, 20, 30 minutes; 1, 2, 6, 24 hours; and 3, 7, 28 days to determine
      systemic Rapa levels. Rapa levels in whole blood, arterial wall, heart, renal and
      liver tissues were determined by high-performance liquid chromatography/mass
      spectroscopy. RESULTS: Peak whole blood concentration (Cmax), time to peak
      concentration (tmax), elimination half-life (t1/2beta), area under the curve
      (AUC), and apparent systemic clearance (Cl/F) were (10.91 +/- 1.28) ng/ml, (2.0
      +/- 0.2) hours, (7.25 +/- 0.63) hours, (1.15 +/- 0.11) ng x h x ml(-1), and (180
      +/- 12) ml x h(-1) x kg(-1), respectively. More than 95% Rapa detected is
      localized in the coronary artery surrounding the stent and heart. CONCLUSION:
      Stent-based delivery of Rapa via a copolymer stent is feasible and safe. This
      strategy holds promise for the prevention of stent restenosis.

PMID- 15498366
TI  - Killing effect of coexpressing cytosine deaminase and thymidine kinase on rat
      vascular smooth muscle cells.
AB  - BACKGROUND: Vascular smooth muscle cell (VSMC) proliferation following arterial
      injury plays a critical role in a variety of vascular proliferative disorders,
      such as atherosclerosis and restenosis after balloon angioplasty. Herpes simplex
      virus-thymidine kinase (HSV-TK)/ganciclovir (GCV) and E. coli cytosine deaminase
      (CD)/5-fluorocytosine (5-Fc) suicide gene systems have been successfully employed
      in cardiovascular gene therapy, respectively. We reasoned that coexpression of
      both HSV-TK with CD suicide genes would lead to increased cell killing. To test
      this imagine, the adenoviral vectors expressing TK and/or CD genes were developed
      and tested on vascular smooth muscle cells. METHODS: Adenoviral vectors,
      including Ad-EF1alpha-CD-cytomegalovirus (CMV)-TK coexpressing both CD and TK
      double suicide genes, Ad-EF1alpha-CD and Ad-CMV-TK expressing CD and TK
      respectively, and control vector Ad-CMV-LacZ, were constructed and prepared with
      homologous recombination in RecA + E. coli cells. Integration and expression of
      CD and/or TK gene were identified by PCR and Western blot. Primary cultured VSMCs
      were infected at a multiplicity of infection (MOI) of 20 with exposure to their
      matching prodrugs 5-Fc and GCV. Cell mortality was measured by methyl thiazolyl
      tetrazolium (MTT) assays. Flow cytometry analysis was used to detect cell death.
      Apoptotic cells were analyzed using Hoechst 33342 fluorescence dye as a DNA
      probe. Genomic DNA cleavage of apoptotic VSMCs was tested by agarose gel
      electrophoresis. RESULTS: Recombinant adenovirus expressing CD and/or TK suicide
      genes were successfully constructed. Both single and double suicide genes could
      be integrated into adenoviral genome and expressed. Cytotoxic effects of Ad
      EF1alpha-CD-CMV-TK double suicide genes combined with 5-Fc and GCV were higher
      than those of Ad-CMV-TK and Ad-EF1alpha-CD single gene groups. The rate of cell
      survival was only (9 +/- 3)% in the Ad-EF1alpha-CD-CMV-TK group, but (37 +/- 3)%
      in the Ad-CMV-TK and (46 +/- 4)% in the Ad-EF1alpha-CD groups (P < 0.05). Flow
      cytometry analysis indicated that the killing mechanisms of the groups were
      different. Necrosis and apoptosis were involved in the mechanism of the double
      gene group. Based on the DNA stainability with Hoechst 33342, the apoptotic rates
      of VSMCs in the Ad-EF1alpha-CD-CMV-TK [(11.0 +/- 2.1)%] and Ad-CMV-TK [(12.0 +/-
      2.2)%] groups were higher than those in Ad-CMV-LacZ [(1.2 +/- 0.11)%] and Ad
      EF1alpha-CD [(5.0 +/- 1.8)%] groups (P < 0.05, respectively). DNA smear could be
      observed in both Ad-CMV-TK and Ad-EF1alpha-CD-CMV-TK groups after administration
      of prodrugs. CONCLUSIONS: The killing effect on rat VSMCs mediated by adenoviral
      CD/TK double suicide genes is superior to that of single suicide gene. The
      killing mechanism of recombinant adenovirus coexpressing CD/TK double suicide
      genes is mainly through cytotoxic effect and apoptosis.

PMID- 15498367
TI  - Effects of transforming growth factor-beta1 and signal protein Smad3 on rat
      cardiomyocyte hypertrophy.
AB  - BACKGROUND: SMAD proteins have recently been identified as the first family of
      putative transforming growth factor-beta1 (TGF-beta1) signal transducers. This
      study was to investigate the effects of TGF-beta1 and signal protein Smad3 on rat
      cardiac hypertrophy. METHODS: The incorporation of [(3)H]-leucine was measured to
      determine the hypertrophy of cardiomyocyte incubated with different doses of TGF
      beta1 in cultured neonatal cardiomyocytes. The model of rat cardiac hypertrophy
      was produced with constriction of the abdominal aorta. At different times after
      the operation, rats were killed, and their left ventricular mass index (LVMI)
      determined. The mRNA expression of TGF-beta1 and Smad3 of cultured cells and
      hypertrophic left ventricles were assessed by RT-PCR. The protein expression of
      Smad3 was assessed by Western blot. RESULTS: In cultured neonatal cardiomyocytes,
      TGF-beta1 significantly promoted incorporation of [(3)H]-leucine. With the
      concentration of 3 pg/L, it increased the expression of Smad3 in mRNA and protein
      levels after 15 minutes, and continued for up to 8 hours of cultured
      cardiomyocytes. The LVMI and the expression of TGF-beta1 (mRNA) and Smad3 (mRNA
      and protein) of hypertrophic left ventricle were increased by day 3 after the
      operation and continued to the 4th week. The peak expression of these was in the
      second week after operation. CONCLUSION: TGF-beta1 has positive effects on rat
      cardiomyocyte hypertrophy. Signal protein Smad3 could be related to the
      pathologic progression of rat cardiac hypertrophy.

PMID- 15498368
TI  - Low-power Helium-Neon laser irradiation enhances the expression of VEGF in murine
      myocardium.
AB  - BACKGROUND: Low-power helium-neon (He-Ne) lasers have been increasingly widely
      applied in the treatment of cardiovascular diseases, and its vasodilation effect
      has been proven. The aim of this study was to determine the effects of low-power
      He-Ne laser irradiation directed at the precardial region of Wistar rats on
      capillary permeability in the myocardium and the expression of myocardial
      vascular endothelial growth factor (VEGF). METHODS: Sixteen rats were divided
      randomly into control and irradiated groups (n = 8, each). A He-Ne laser (632.8
      nm) was applied to the irradiated group with a dose of 60.5 J/cm(2). Ferritin was
      perfused into the left femoral vein and capillary permeability was examined under
      an electron microscope. VEGF expression in the myocardium was investigated by
      immunohistochemical methods, RT-PCR, and image analysis. RESULTS: The
      ultrastructures of the myocardial capillaries were examined. Compared to the
      control group, more high-density granules (ferritin), which were present within
      the capillary endothelium and the mitochondrions of myocardial cells in the
      internal layer of the myocardium, were observed in the irradiated group. VEGF
      staining of the myocardium was stronger in the irradiated group than that in the
      control group. The optic density of the irradiated group (0.246 +/- 0.015) was
      significantly higher than that of the control group (0.218 +/- 0.012, P < 0.05).
      Finally, the levels of RT-PCR products of VEGF165 mRNA were 2.79 times higher in
      irradiated rats than in the control rats. CONCLUSIONS: Our study demonstrates
      that He-Ne laser irradiation (in doses of 60.5 J/cm(2)) increases myocardial
      capillary permeability and the production of VEGF in myocardial microvessels and
      in myocardium. Our study provides experimental morphological evidence that
      myocardial microcirculation can be improved using He-Ne laser irradiation.

PMID- 15498369
TI  - Genetic polymorphism in matrix metalloproteinase-9 and the susceptibility to
      chronic obstructive pulmonary disease in Han population of south China.
AB  - BACKGROUND: There are many candidate genes for chronic obstructive pulmonary
      disease (COPD). Matrix metalloproteinase-9 (MMP-9) plays an essential role in
      tissue remodeling and repair associated with development of COPD. In this study
      we investigated the correlation between MMP-9 gene polymorphism and COPD
      susceptibility in the Han population of South China. METHODS: We examined the
      frequency of polymorphic genotypes of the MMP-9 promoter (-1562C/T) in 100 COPD
      patients and 98 healthy smokers by restriction fragment length polymorphism.
      RESULTS: The frequencies of polymorphic genotypes in promoters of MMP-9 were C/C
      86%, C/T 14% in COPD group; and C/C 98%, C/T 2% in the control group. There were
      significant differences between the two groups (P < 0.01). The allele frequencies
      were also significantly different between the COPD group and the control group (C
      allele frequency: 93% vs 99%, T allele frequency: 7% vs 1%, P < 0.05
      respectively). CONCLUSION: The genetic polymorphism in promoters of MMP-9 gene is
      associated with the susceptibility to COPD in the Han population of South China.

PMID- 15498370
TI  - Quantification of plasma DNA as a screening tool for lung cancer.
AB  - BACKGROUND: Recent studies suggest that circulating DNA may be a potential tumor
      marker for lung cancer, but most of these studies are conducted between healthy
      controls and lung cancer patients, with few or no benign lung disease patients
      included. The objective of this study was to evaluate the performance of plasma
      DNA quantification in discriminating lung cancer from the healthy and benign lung
      disease. METHODS: Plasma DNA was extracted with a QIAamp DNA Blood Midi kit and
      quantified by a PicoGreen dsDNA quantitation kit in 44 healthy individuals, 36
      benign lung disease patients and 67 lung cancer patients. Discrimination power
      was evaluated by the receiver operating characteristic curve. RESULTS: Plasma DNA
      values were significantly increased in lung cancer patients, especially in those
      with metastases, and in benign lung disease patients compared with that in the
      healthy individuals (P < 0.001, respectively). The values in lung cancer patients
      were significantly increased compared with that in the benign lung disease
      patients (P < 0.001). The area under the curve was 0.96 [95% confidence interval
      (CI) 0.92 - 0.99] for the healthy versus lung cancer, 0.73 (95% CI 0.64 - 0.83)
      for lung cancer versus benign lung disease, and 0.86 (95% CI 0.80 - 0.91) for
      lung cancer versus the healthy and benign lung disease. CONCLUSIONS: Plasma DNA
      quantification has a strong power to discriminate lung cancer from the healthy
      and from the healthy and benign lung disease, less power to discriminate lung
      cancer from benign lung disease. Plasma DNA quantification may be useful as a
      screening tool for lung cancer.

PMID- 15498371
TI  - Pulmonary functional MRI: an animal model study of oxygen-enhanced ventilation
      combined with Gd-DTPA-enhanced perfusion.
AB  - BACKGROUND: The assessment of regional pulmonary ventilation and perfusion is
      essential for the evaluation of a variety of lung disorders. Pulmonary
      ventilation MRI using inhaled oxygen as a contrast medium can be obtained with a
      clinical MR scanner, without additional equipment, and has been demonstrated to
      be a feasible means of assessing ventilation in animal models and some clinical
      patients. However, few studies have reported on MR ventilation-perfusion imaging.
      In this study, we evaluated the usefulness of oxygen-enhanced ventilation in
      combination with first-pass Gd-DTPA-enhanced perfusion MRI in a canine model of
      pulmonary embolism and airway obstruction. METHODS: Peripheral pulmonary
      embolisms were produced in eight dogs by intravenous injection of gelfoam strips
      at the pulmonary segmental arterial level, and airway obstructions were created
      in five of the dogs by inserting a self-designed balloon catheter into a
      secondary bronchus. Oxygen-enhanced MR ventilation images were produced by
      subtracting images from before and after inhalation of pure oxygen. Pulmonary
      perfusion MR images were acquired with a dynamic three-dimensional fast gradient
      echo sequence. MR ventilation and perfusion images were read and contrasted with
      results from general examinations of pathological anatomy, ventilation-perfusion
      scintigraphy, and pulmonary angiography. RESULTS: Regions identified as having
      airway obstructions matched using both MR ventilation and perfusion imaging, but
      regions of pulmonary embolisms were mismatched. The area of airway obstruction
      defects was smaller using MR ventilation imagery than that using ventilation
      scintigraphy. Abnormal perfusion regions due to pulmonary embolisms were divided
      into defective regions and reduced regions based on the time course of signal
      intensity changes. In the diagnosis of pulmonary embolisms with the technique of
      ventilation and perfusion MRI, sensitivity and specificity were 75.0% and 98.1%,
      respectively, and the diagnostic results of this MRI technique were in agreement
      with the results of ventilation-perfusion scintigraphy and pulmonary angiography
      (K: 0.899, 0.743). CONCLUSIONS: Oxygen-enhanced ventilation in combination with
      pulmonary perfusion MRI can be used to diagnose abnormalities of airways and
      blood vessels in the lungs, and can provide regional functional information with
      high spatial and temporal resolution. This method possesses great potential value
      for clinical applications.

PMID- 15498372
TI  - Case-control study and transmission/disequilibrium tests of the genes encoding
      GABRA5 and GABRB3 in a Chinese population affected by childhood absence epilepsy.
AB  - BACKGROUND: Childhood absence epilepsy (CAE) is one of the most frequently
      recognized syndromes among the idiopathic generalized epilepsies (IGEs). CAE is
      considered to be a genetic disease, with a possible polygenic inheritance
      pattern. The genes responsible for CAE have not been identified yet. The object
      of this study was to investigate whether or not CAE is associated with the gene
      encoding the gamma-aminobutyric acid (GABA) type-A receptor subunits alpha5
      (GABRA5) and beta3 (GABRB3) in a Chinese population. METHODS: Five microsatellite
      DNA repeats, 69CA, 85CA, 155CA1, 155CA2, and A55CA1, adjoining chromosome 15q11
      q13, were used as genetic markers. Both case-control study and
      transmission/disequilibrium tests (TDTs), as well as fluorescence-based semi
      automated genotyping techniques, were used in 90 CAE patient-mother-father trios
      and 100 normal controls of Han ethnicity to conduct association analysis.
      RESULTS: The frequencies of allele 5 of 69CA, alleles 2 and 8 of 85CA, alleles 6
      and 7 of 155CA1, allele 2 of 155CA2, and alleles 1 and 11 of A55CA1 were
      significantly higher in CAE patients than in normal controls. To prevent spurious
      associations arising from population admixture, we further conducted TDT tests in
      the 90 CAE trios. The results of TDT analysis further suggested that
      microsatellite DNA repeats 85CA, 155CA1, and 155CA2 were associated with CAE.
      CONCLUSIONS: GABA type-A receptor subunit genes GABRA5 and GABRB3 may be either
      directly involved in the etiology of CAE in the Chinese population or in linkage
      disequilibrium with disease-predisposing sites.

PMID- 15498373
TI  - Efficacy of acupuncture and moxibustion in treating Bell's palsy: a multicenter
      randomized controlled trial in China.
AB  - BACKGROUND: Bell's palsy involves acute facial paralysis due to inflammation of
      the facial nerve. Acupuncture and moxibustion (acu-moxi) is beneficial in
      treating facial palsy. In order to verify the efficacy of acu-moxi on Bell's
      palsy, a randomized single-blind, multicenter clinical trial was performed.
      METHODS: A total of 480 patients from four clinical centers were involved in this
      trial, of whom 439 completed the trial and 41 did not. All patients were randomly
      assigned to either the control group or to one of two treatment groups. The
      control group was treated with prednisone, vitamin B1, vitamin B12, and dibazole;
      the treatment groups were treated either with acu-moxi alone or in combination
      with prednisone, Vitamin B1, vitamin B12, and dibazole. Symptoms and signs, the
      House-Brackmann scale, and facial disability index (FDI) scores were assessed and
      determined both pre- and post-treatment to evaluate the effectiveness of the
      treatment methods. RESULTS: The characteristics of the control and two treatment
      groups were comparable without statistically significant differences before
      treatment. There were significant differences between the control and treatment
      groups after treatment (chi(2) = 15.265, P = 0.018). According to evaluations
      based on the House-Brackmann scale and FDI scores, the effectiveness of treatment
      in the two treatment groups was better than in the control group and was most
      effective in patients receiving acu-moxi treatment alone (Z = -2.827, P = 0.005).
      CONCLUSION: The efficacy of acu-moxi treatment for Bell's palsy is verified
      scientifically.

PMID- 15498374
TI  - Correlation between neuronal injury and Caspase-3 after focal ischemia in human
      hippocampus.
AB  - BACKGROUND: Cerebral ischemia is a significant clinical problem, and cerebral
      ischemia usually causes neuron injury such as apoptosis in various brain areas,
      including hippocampus. Cysteinyl aspartate-specific protease (Caspases) are
      fundamental factors of apoptotic mechanism. Caspase-3 inhibitors show effect in
      attenuating brain injury after ischemia. But all the results were from animal
      models in research laboratories. This study aimed at investigating the
      correlation between the change of ischemic neuronal injury and Caspase-3 post
      ischemia in human hippocampus. METHODS: We selected and systematized 48 post
      mortem specimens from 48 patients, who died of cerebral infarction. Morphological
      change was firstly analyzed by observing hematoxyline/eosin-staining hippocampal
      sections. The expression of Caspase-3 was investigated using the methods of in
      situ hybridization and immunohistochemistry. Terminal deoxynucleotidyl
      transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick-end labeling
      (TUNEL) method was used to clarify the involvement of Caspase-3 in neuron death.
      The loss of MAP 2 (MAP-2) was applied to judging the damaged area and degree of
      neuronal injury caused by ischemia. RESULTS: In the CA1 sector of hippocampus,
      Caspase-3 immunostaining modestly increased at 8 hours [8.05/high-power field
      (hpf)], dramatically increased at 24 hours (24.85/hpf), decreased somewhat after
      72 hours. Caspase-3 mRNA was detectable at 4 hours (6.75/hpf), reached a maximum
      at 16 hours (17.60/hpf), faded at 72 hours. TUNEL-positive cells were detectable
      at 24 hours (10.76/hpf), markedly increased at 48 - 72 hours. The loss of MAP-2
      was obviously detected at 4 hours, progressed significantly between 24 and 72
      hours; MAP-2 immunoreactivity was barely detectable at 72 hours. Before 72 hours,
      the Caspase-3 evolution was related with the upregulation of TUNEL and the loss
      of MAP-2. The positive correlation between Caspase-3 mRNA and TUNEL was
      significant at the 0.05 level (correlation coefficient was 0.721); the negative
      correlation between Caspase-3 mRNA and MAP-2 was significant at the 0.05 level
      (correlation coefficient is 0.857). In the early stage (before 72 hours), the
      staining of Caspase-3 mRNA and immunohistochemistry was predominantly present in
      cytoplasm; the staining of TUNEL was predominantly localized in nucleus. At 4 -
      16 hours, most neurons in hippocampal CA1 areas had relatively normal morphology;
      at 24 - 48 hours, neurons showed apoptotic morphology; at 72 hours, most cells
      showed significantly pathological morphology. CONCLUSIONS: There exist a time
      dependent evolution of neuronal damage after hippocampal ischemia in human brain,
      which was characterized by its close correspondence to Caspase-3.

PMID- 15498375
TI  - Lipoprotein glomerulopathy: clinical features and pathological characteristics in
      Chinese.
AB  - BACKGROUND: Lipoprotein glomerulopathy (LPG), once recognized as a rare
      glomerular disease, has been reported around the world in recent years. In this
      study, we reported 8 patients of LPG and aimed to explore the clinical features
      and pathological characteristics of LPG under light microscope,
      immunofluorescence staining, and electron microscope. METHODS: Clinical
      manifestations were recorded on the day of renal biopsy. Biochemical patterns of
      lipids and lipoproteins were detected by routine examination. Plasma
      concentrations of apo B and apo E were determined by radial immunodiffusion
      assays. Biopsy specimens were then processed for light microscopy,
      immunohistochemical staining for immunoglobulins and complement components, and
      electron microscopy. Glomerular deposition of apo A, B, and E were detected using
      monoclonal antibodies on cryostatic sections. RESULTS: All of the eight patients
      presented with edema, microscopic hematuria, severe proteinuria, anemia, and
      enlarged kidney size. Biochemical profiles revealed high levels of triglycerides,
      apo B, and apo E. We noted increments of glomerular size and lipoprotein thrombi
      occupying capillary lumina in the glomeruli of all patients. Immunofluorescence
      staining showed that the thrombi were strongly positive for apo A, B, and E.
      Granules and various sizes of vacuoles were observed in the thrombi under
      electron microscope. CONCLUSION: Compared with previous reports on LPG in other
      countries, unique clinical and pathological features were found in this group of
      Chinese LPG patients.

PMID- 15498376
TI  - Effect of different iodine intake on schoolchildren's thyroid diseases and
      intelligence in rural areas.
AB  - BACKGROUND: Reports are increasingly appearing on the side effects caused by
      excessive iodine intake. Our objective was to find out whether iodine excess
      would impair the thyroid function and intelligence of schoolchildren in rural
      areas of China. METHODS: A comparative epidemiological study was made on thyroid
      function and intelligence of the schoolchildren in the areas of low, moderate or
      excessive intake of iodine. In the area of low intake of iodine (Panshan,
      Liaoning province, median urinary iodine (MUI) was 99 microg/L), of moderate
      intake of iodine (Zhangwu, Liaoning Province, MUI was 338 microg/L) and of
      excessive intake of iodine (Huanghua, Hebei Province, MUI was 631 microg/L). The
      numbers of schoolchildren from each area selected to take part in a Chinese
      version of Raven's Test were 190, 236 and 313, respectively, and then 116, 110
      and 112 of them were tested for thyroid function, thyroid autoantibody (TAA) and
      urinary iodine (UI). RESULTS: There were no significant differences in the
      incidences of overt hyperthyroidism, subclinical hyperthyroidism and overt
      hypothyroidism in Panshan, Zhangwu and Huanghua. But significant differences were
      found in the incidences of subclinical hypothyroidism (P = 0.001) in these three
      areas. The incidences of subclinical hypothyroidism in Huanghua and Zhangwu were
      4.76 and 3.37 times higher than that in Panshan. TAA were negative in all the
      schoolchildren with subclinical hypothyroidism except for one. No significant
      difference was found among the rates of thyroid peroxidase antibody (TPOAb) and
      thyroglobulin antibody (TGAb) in these three areas. Mean serum thyroglobulin (TG)
      value of Huanghua was markedly higher than those of the other two (P = 0.02).
      Mean serum TG value of Zhangwu was higher than that of Panshan but the difference
      was not significant. Mean IQ value of the schoolchildren in Huanghua was markedly
      higher than that for Zhangwu (P = 0.001). Mean IQ value of the schoolchildren in
      Panshan was lower than that of Huanghua and higher than that of Zhangwu but,
      again, the differences were not significant. CONCLUSIONS: The increase of iodine
      intake may increase the risk for schoolchildren of subclinical hypothyroidism. In
      the area of iodine excess, most of the subclinical hypothyroidism cases are not
      of autoimmune origin. No obvious effect of excess iodine was found on mental
      development of schoolchildren.

PMID- 15498377
TI  - Effects of timely insulin treatment on protection of beta cells in a rat model of
      type 2 diabetes mellitus.
AB  - BACKGROUND: Insulin treatment plays a key role in management of diabetes
      mellitus. Clinical researches showed that extra improvements in restoration of
      insulin secretion of pancreatic beta cells were found in patients with newly
      diagnosed type 2 diabetes. The purpose of this study was to investigate the
      effects of early insulin treatment on insulin mRNA expression and morphological
      alterations of beta cells in a Sprague Dawley (SD) rat model of type 2 diabetes.
      METHODS: A rat model of type 2 diabetes mellitus (T2DM) was induced by a high fat
      diet (high energy, HE) and low doses of streptozotoxin (STZ, 40 mg/kg). A group
      of diabetic rats was then injected with protamine zinc insulin [PZI, 1 - 2 U x
      kg(-1) x d(-1)] for one week. Insulin mRNA expression, morphological features of
      pancreatic islets, and metabolic parameters were examined in rats using reverse
      transcriptase-polymerase chain reaction (RT-PCR), immunohistochemistry, and other
      techniques. RESULTS: In insulin-treated diabetic rats, insulin mRNA levels
      prominently increased by 81.3% (P < 0.05), as compared with untreated diabetic
      rats. Moreover, timely insulin treatment noticeably improved the insulin content
      of beta cells, with an increase of 10.2% (P < 0.05), despite a slight reduction
      in fasting blood glucose (FBG), triglyceride (TG), and free fatty acid (FFA)
      levels, as compared to an untreated diabetic group. CONCLUSION: Insulin treatment
      at the onset of T2DM effectively improves insulin synthesis, as confirmed by
      morphological changes to beta cells in a rat model of type 2 diabetes.

PMID- 15498378
TI  - Relations of proliferative activities of gastric carcinoma cells to lymphatic
      involvement, venous invasion and prognosis.
AB  - BACKGROUND: This study was to evaluate bivariate bromodeoxyuridine (BrdUrd)/DNA
      flow cytometric analysis in detection of gastric carcinoma and to study the
      relations of cellular BrdUrd labeling indices (LI), G2/M-phase fraction (G2/MPF)
      and DNA ploidy pattern to lymphatic involvement, venous invasion and prognosis.
      METHODS: Fresh tumor samples from 60 patients with gastric carcinoma were
      analyzed by bivariate BrdUrd/DNA flow cytometry. The results were correlated with
      lymphatic vessel invasion, lymphatic node metastasis, the number of metastatic
      lymphatic nodes, and venous invasion. Propidium iodide (PI) was used as a
      fluorescent probe for total cellular DNA, and a monoclonal antibody against
      BrdUrd was used as a probe for BrdUrd incorporated into DNA. Fluorescent-labeled
      goat anti-mouse antibody was used as a second antibody. S-phase fractions were
      measured by in vitro BrdUrd labeling, and DNA ploidy and G2/MPF were also
      measured. Comparison of survival was performed with the log-rank test, the Chi
      square test for qualitative data, and Student's t test for quantu data. RESULTS:
      BrdUrd LI and G2/MPF values were significantly higher in tumors with lymphatic
      vessel invasion than in those without invasion respectively (P < 0.01); the
      patients who had tumors with lymphatic vessel invasion showed a significantly
      poor prognosis (P < 0.01). Both BrdUrd LI and G2/MPF values were significantly
      higher in tumors with lymphatic node metastasis than in those without metastasis
      (P < 0.01). A statistical significant difference was noted in the 5-year survival
      rates between the patients with lymph node metastasis and those without
      metastasis. Compared with diploid carcinoma, the incidence of lymph node
      metastasis was significantly higher in aneuploid carcinoma (P < 0.05), and the
      patients with aneuploid carcinoma showed a significantly poor prognosis (P <
      0.05). BrdUrd LI was significantly higher in patients with more than 5 metastatic
      lymph nodes than those with 1 - 4 metastatic lymph nodes (P < 0.05) and those
      without metastasis (P < 0.01). G2/MPF values in those patients either with more
      than 5 metastatic lymph nodes or 1 - 4 metastatic lymph nodes were higher than
      those without metastasis (P < 0.01 and P < 0.05). A statistical significance was
      seen in the 5-year survival rates among the patients with no metastatic lymph
      node, 1 - 4 metastatic nodes and more than 5 metastatic nodes (P < 0.01). G2/MPF
      values were significantly higher in patients with venous invasion than in those
      without invasion (P < 0.01). CONCLUSIONS: Positive correlations exist between
      cellular BrdUrd LI, G2/MPF with lymphatic involvement and prognosis, and DNA
      aneuploid with lymphatic involvement and prognosis. The same was true between
      G2/MPF value and venous invasion in gastric carcinoma.

PMID- 15498379
TI  - Biological characteristics of breast carcinomas with neuroendocrine cell
      differentiation.
AB  - BACKGROUND: The aim of this study was to investigate DNA content and expression
      of c-erbB-2, PS2, and prostate-specific antigen (PSA) proteins in breast
      carcinomas with neuroendocrine (NE) cell differentiation. METHODS: Chromogranin,
      c-erbB-2, PS2, and PSA in 131 samples of breast cancer were detected
      immunohistochemically. Classic Feulgen staining image analysis techniques were
      used to quantify DNA content in 81 of the breast cancer samples. RESULTS: The c
      erbB-2 positive rate in breast carcinoma samples containing neuroendocrine cells
      was 37.5% and the rate of high expression of c-erbB-2 (++ or +++) was 33.3%, both
      significantly lower than that in breast carcinomas without neuroendocrine cells
      (62.6% and 68.7%, respectively, P < 0.05). The rates of positive PS2 and PSA
      expression in breast carcinoma samples containing neuroendocrine cells were 72.2%
      and 55.0%, respectively, both significantly higher than that in breast carcinoma
      samples without neuroendocrine cells (45.0% and 16.4%, respectively, P < 0.05).
      In NE(+) samples, the integral optical density, DNA index, DNA stemline peak, > 5
      c aneuploidy cells, and rate of aneuploidy among cells were all lower than that
      in NE(-) breast carcinomas (P < 0.01). In NE(+) grade I or II breast carcinomas,
      these indices were also all lower than that in the NE(-) breast carcinoma samples
      (P < 0.01). CONCLUSION: Breast carcinomas with neuroendocrine differentiation
      have a lower rate of malignancy. Neuroendocrine differentiation could serve as a
      prognostic marker in clinical practice.

PMID- 15498380
TI  - Expression levels and significance of hypoxia inducible factor-1 alpha and
      vascular endothelial growth factor in human colorectal adenocarcinoma.
AB  - BACKGROUND: Hypoxia-inducible factor 1 (HIF-1), a transcription factor, is
      overexpressed in common human cancers and their metastases. This study aimed at
      determining the expression levels of HIF-1alpha and vascular endothelial growth
      factor (VEGF) in SW480 cells and in colorectal adenocarcinoma tissue and
      ascertaining whether HIF-1alpha and VEGF play important roles in tumor
      angiogenesis. METHODS: HIF-1alpha mRNA expression was analyzed using in situ
      hybridization and RT-PCR. HIF-1alpha and VEGF protein were detected in SW480
      cells and colorectal adenomas and adenocarcinomas by immunohistochemistry using
      streptavidin/peroxidase (SP). Western blot was used to detect HIF-1alpha protein
      extracted from SW480 cells. Microvessel density (MVD) in colorectal carcinomas
      was determined by anti-CD34 immunostaining in colorectal carcinomas. RESULTS:
      Optical density values representing HIF-1alpha mRNA expression levels were found
      to be significantly higher in SW480 cells in hypoxic conditions than in cells
      under normoxic conditions (P < 0.05) or in hypoxic conditions but treated with
      genistein (P < 0.05). The levels of HIF-1alpha and VEGF protein expression in
      SW480 cells were significantly higher in the hypoxia group than in the normoxia
      group (P < 0.01, P < 0.05, respectively) and hypoxia/genistein group (P < 0.01, P
      < 0.05, respectively). The positive expression rates of HIF-1alpha mRNA changed
      dramatically when comparing colorectal adenomas with adenocarcinomas of different
      Dukes' stages (P < 0.05). HIF-1alpha mRNA was also expressed at higher levels in
      adenocarcinomas than that in adenomas (P < 0.01). HIF-1alpha protein expression
      correlated significantly with VEGF protein expression and MVD. CONCLUSIONS:
      Hypoxia induces the expression of HIF-1alpha and VEGF in colorectal
      adenocarcinomas. HIF-1alpha may play an important role in angiogenesis and tumor
      progression by regulating the expression of VEGF in human colorectal carcinomas.

PMID- 15498381
TI  - Neoadjuvant intraarterial chemotherapy and embolization in treatment of advanced
      ovarian epithelial carcinoma.
AB  - BACKGROUND: The purpose of the study was to evaluate the role of neoadjuvant
      chemotherapy and embolization via the anterior branches of the bilateral internal
      iliac arteries in treating patients with advanced ovarian epithelial carcinoma.
      METHODS: Forty-two patients with advanced ovarian epithelial carcinoma (study
      group) were treated via the anterior branches of the bilateral internal iliac
      arteries after cytoreductive surgery and 7 courses of adjuvant platinum-based
      combination chemotherapy. Primary cytoreductive surgery was performed in 43
      patients with advanced ovarian epithelial carcinoma (control group), and then
      followed by 8 courses of adjuvant platinum-based combination chemotherapy. The
      rate of optimal cytoreductive surgery, survival rate, blood loss during operation
      and operative time were investigated in the two groups. Statistical significance
      was assessed using Student's t test, the Chi-square test and the log-rank test.
      RESULTS: In the study group, the rate of optimum debulking after platinum-based
      chemotherapy and embolization via the anterior branches of the bilateral internal
      iliac arteries was 71.43% (30/42) (chi(2) = 10.06, P < 0.005), and 9 (21.43%) of
      the 42 patients showed no gross residual disease after surgery. Blood loss and
      operative time were significantly decreased in the study group as compared with
      those in the control group (665.24 +/- 37.61 ml: 849.31 +/- 41.20 ml, t(1) =
      33.21, P(1) < 0.001; 4.23 +/- 0.21 hours: 6.15 +/- 0.38 hours, t(2) = 28.92, P(2)
      < 0.01). In the study group, the mean survival time and the median overall
      survival were 33.66 months (95% CI, 24.73 to 42.58) and 26.00 months (95% CI,
      19.22 to 32.78), respectively. The median disease-free interval was 18.20 months.
      In the control group, the mean survival time and the median overall survival were
      32.38 months (95% CI, 24.92 to 39.84) and 25.00 months (95% CI, 22.80 to 27.20),
      respectively. The median disease-free interval was 14.20 months. The overall
      survival rates were not significantly different between the two groups (chi(2) =
      6.48, P > 0.05). CONCLUSIONS: Neoadjuvant platinum-based combination chemotherapy
      and embolization via the anterior branches of the bilateral internal iliac
      arteries is an alternative treatment for patients with advanced ovarian
      epithelial carcinoma, in whom the chance of optimal cytoreductive surgery is low.
      The treatment can reduce blood loss, decrease operative time, and increase the
      rate of optimal cytoreductive surgery; but the median survival can't be improved
      significantly.

PMID- 15498382
TI  - Electron paramagnetic resonance in monitoring of nitric oxide production after
      kidney transplantation in rats.
AB  - BACKGROUND: Much research has been focused on ischemia/reperfusion injury (IRI)
      to the transplanted organs. As a free radical, nitric oxide (NO) plays an
      important role in IRI. In this study, the production of NO and its functions
      during IRI were monitored in rat models after allotransplantation of kidney
      grafts. METHODS: Of 75 male LEW rats, 30 served as donors, and the remaining 45
      rats were divided into three groups (15 rats in each group): controls (group 1),
      kidney allotransplantation followed by bilateral nephrectomy during reperfusion
      (group 2), 2 hours before operation, donors and recipients were treated with N(G)
      nitro L-arginine methyl ester (L-NAME), a NO synthase inhibitor, at a dose of 30
      mg/kg (group 3). Bilateral nephrectomies were performed while kidney grafts were
      reperfused. The kidney grafts were hypothemically stored for 24 hours. The
      production of NO before and after reperfusion was measured by electron
      paramagnetic resonance (EPR). The creatinine level, the glomerular filtration
      rate (GFR) and the protein carbonyl content in tissue samples were recorded on
      the first and the fifth day after operation. The data were evaluated by one-way
      analysis of variance. Differences were considered to be statistically significant
      when a P value was less than 0.05. RESULTS: After reperfusion for 15 minutes, the
      production of NO increased remarkably and kept increasing till 120 minutes, after
      which the level returned to normal. In group 3, which was pretreated with L-NAME,
      creatinine levels were higher than those in group 2 at the 24th hour (4.10 +/-
      0.50 mg/dl vs. 3.77 +/- 0.42 mg/dl, P < 0.05) and the 120th hour (3.19 +/- 0.79
      mg/dl vs. 2.22 +/- 0.53 mg/dl, P < 0.05). GFR levels in group 3 were lower than
      those in group 2 at the 24th hour (0.50 +/- 0.12 ml/min vs. 0.71 +/- 0.19 ml/min,
      P < 0.05) and the 120th hour (0.59 +/- 0.38 ml/min vs. 1.27 +/- 0.23 ml/min, P <
      0.01). The content of protein carbonyl in tissue samples of group 3 was lower
      than that in group 2 at the 24th hour (29.01 +/- 7.02 nmol/mg protein vs. 49.39
      +/- 13.13 nmol/mg protein, P < 0.05), but was higher than that at the 120th hour
      (75.71 +/- 16.74 nmol/mg protein vs. 57.93 +/- 15.32 nmol/mg protein, P < 0.05).
      CONCLUSIONS: After transplantation of hypothemically stored kidney grafts, the
      increased NO production in the early stage has protective effects on the
      transplanted kidney. Application of L-NAME to inhibit NO production is harmful to
      the recovery of the renal functions of kidney grafts.

PMID- 15498383
TI  - Induction of T-cell immunity against Epstein-Barr virus-associated tumors by
      means of adenovirally transduced dendritic cells.
AB  - BACKGROUND: Dendritic cells (DCs) are the most powerful antigen-presenting cells
      to induce specific T-cell immunity, which plays an important role in the body's
      anti-tumor responses. In this study, we assessed the feasibility and efficacy of
      inducing T-cell immunity against Epstein-Barr virus (EBV)-associated tumors in
      vivo using dendritic cells transfected with EBV latent membrane 2A (LMP2A)
      recombinant adenovirus. METHODS: Cytokine-activated bone marrow-derived DCs
      transfected with EBV LMP2A recombinant adenovirus were infused into BALB/c mice.
      Splenic cytotoxic T-cell responses were evaluated by cytotoxicity and interferon
      gamma production assays. in vivo immune protection was then assessed in the mice
      tumor models implanted with tumor cells expressing EBV LMP2A. RESULTS: DCs
      transfected with EBV LMP2A recombinant adenovirus could strongly induce EBV LMP2A
      specific cytotoxic T-cell responses and upregulate interferon-gamma production in
      vivo. Vaccination using these DCs led to prolongation of overall survival rates
      in the mice tumor models and retarded tumor growth. CONCLUSIONS: The results
      suggest that DCs transfected with EBV LMP2A recombinant adenovirus can serve as a
      feasible and effective tool for eliciting LMP2A-specific cytotoxic T-cell
      responses against EBV LMP2A in vivo in the treatment of EBV-associated tumors.

PMID- 15498384
TI  - Dose protocols of acetylcholine test in Chinese.

PMID- 15498385
TI  - Systematic examination of DNA variants in the parkin gene in patients with
      Parkinson's disease.

PMID- 15498386
TI  - Specific cytotoxic T lymphocyte responses in Chinese HIV/AIDS patients.

PMID- 15498387
TI  - Suppression of local immune response by GrB expression in gastric cancer cells.

PMID- 15498388
TI  - Marrow stromal cells administrated intracisternally to rats after traumatic brain
      injury migrate into the brain and improve neurological function.

PMID- 15498389
TI  - Effects of flotation therapy on relaxation and mental state.

PMID- 15498390
TI  - Initial application of picture archiving and communication system and its benefit
      analysis.

PMID- 15498391
TI  - Primary hepatic carcinosarcoma: a case report.

PMID- 15498392
TI  - Misdiagnosed ectopic thyroid carcinoma: report of two cases.

PMID- 15498393
TI  - Ipsilateral synchronous renal pelvic transitional cell carcinoma, squamous cell
      carcinoma and adenocarcinoma.

PMID- 15498394
TI  - Ovarian juvenile granulosa cell tumor associated with Maffucci's syndrome: case
      report.

PMID- 15498395
TI  - Disseminated cryptococcosis with extensive subcutaneous nodules in a renal
      transplant recipient.

PMID- 15498396
TI  - Inflammatory myofibroblastic tumour in the left maxillary sinus: a case report.

PMID- 15498398
TI  - [Repercussion on the hemodynamic measurements across a Swan-Ganz catheter with
      the postural changes].
AB  - AIM: Usually hemodynamic measures are done with the patient in dorsal decubitus
      and the bedside at 0 degrees. Our aim has been to evaluate the influence that
      postural changes has in the hemodynamic measures which were carried out with a
      pulmonary artery catheter, so as called Swan-Ganz. MATERIAL AND METHOD: It's a
      prospective study. The same patient is control group and study group. There were
      done tree consecutive measures in each patient. Firstly in dorsal decubitus, then
      right lateral decubitus and finally in left lateral decubitus. Before doing the
      measures after change of posture a thirty minutes period was left in order to
      stabilise the hemodynamical flow. The items of study were, a part of demographic
      ones, cardiac index, pulmonary artery systolic pressure, pulmonary artery
      diastolic pressure, pulmonary artery mean pressure, pulmonary artery occlusion
      pressure, right atrial pressure, systolic arterial pressure, diastolic arterial
      pressure, mean arterial pressure and heart rate. 28 patients were included in the
      study. RESULTS: The age average was 62.5 years (27.05-67.05); a 78.6% were male.
      Who had a NEMS average of 42.4 (39.9-44.9). No difference was found between
      hemodynamic measures in the different postures. CONCLUSIONS: Postural changes in
      stable patients have no influence in pressures and other hemodynamic variables
      measures.

PMID- 15498399
TI  - [Assessment of the efficacy of the implementation of an arterial cannulation
      protocol as quality assurance method].
AB  - AIM: Arterial cannulation is a usual technique in intensive care. With this
      study, we aim to assess the efficacy of the implementation of an arterial
      cannulation protocol. MATERIAL AND METHOD: The study was performed in several
      phases: a first cross-sectional cut-off to assess the technique performed and the
      incidence of complications, without knowledge of the study by the staff involved.
      There was a second phase of development and explanation to the unit staff of a
      protocol performed based on the results obtained and the available evidence. The
      third phase was of reevaluation of the results after the implementation of the
      protocol by a new cross-sectional cut-off without knowledge of the staff.
      RESULTS: In phase 1, a total of 100 arterial cannulations were studied, obtaining
      the existence of a large amount of catheters not fixed by suture (44%) and a
      significant percentage of cases of accidental withdrawal (15%) as fundamental
      results. The protocol was implemented to solve these problems. It stressed the
      suture of all the cannalized catheters. Data on 80 patients and 133 catheters
      have now been gathered. The percentage of catheters that were sutured according
      to the protocol indication was 98%, significantly greater than phase 1 (p<
      0.0001). The number of catheters whose withdrawal reason was accident removal was
      also significantly inferior (4%; p = 0.002). CONCLUSIONS: The implementation of
      an arterial cannulation protocol with a high rate of follow-up by the nursing
      staff has achieved a reduction in the incidence of iatrogenies due to the
      technique.

PMID- 15498402
TI  - [The Framework Convention on Tobacco Control: a response to the globalization of
      a communicated epidemic].

PMID- 15498403
TI  - [Temporal analysis of mortality due to intimate partner violence in Spain].
AB  - OBJECTIVES: To analyze the temporal distribution of mortality due to violence by
      intimate partners (VIP) and to identify possible temporal clusters in women
      deaths by VIP in Spain. METHODS: We performed a descriptive epidemiological study
      based on the VIP deaths included in the database of the Federation of Divorced
      and Separated Women (1998-2003). The epidemic index (EI) was calculated as the
      ratio between the actual number of VIP deaths in a given month from January to
      July 2003 and the median number in the same month in the five preceding years. A
      Poisson model was used to analyze the distribution by years (1998-2002), seasons,
      months, and days. Simple regression analysis was performed with three-monthly
      means. A temporal cluster analysis was also carried out. RESULTS: In 2003, the EI
      of VIP mortality was high in January (EI = 1.6), March (EI = 1.2), May (EI =
      1.5), June (EI = 2), and July (EI = 2.5). Compared with 1998 and Sundays,
      respectively, mortality due to VIP was significantly increased in 2001 (relative
      risk, RR = 1.52; 95% confidence interval [CI], 1.05-2.20) and on Mondays (RR =
      1.77; 95%CI, 1.13-2.76). The regression analyses confirmed an increase between
      the first three-month period of 1998 and the last three-month period of 2001.
      There were no differences between seasons and months. No temporal clusters of
      deaths were detected. CONCLUSIONS: VIP is currently an increasing epidemic in
      Spain with no clear temporal pattern. Political and legal efforts to reduce this
      problem do not seem to be successful.

PMID- 15498404
TI  - [Inequalities in mental health in the working population].
AB  - OBJECTIVES: To analyze inequalities in mental health in the working population by
      gender and professional qualifications and to identify psychosocial risk factors
      and employment conditions related to the mental health of this population.
      METHODS: We performed a cross-sectional study using data from the Barcelona
      Health Survey 2000. The working population aged 16-64 years (2322 men and 1836
      women) was included. Mental health was measured with the General Health
      Questionnaire (GHQ-12). Adjusted odds ratios (aOR) and their 95% confidence
      intervals (CI) were calculated by means of multivariate logistic regression
      models separated by job qualifications and gender. RESULTS: The prevalence of
      poor mental health ranged from 8% among men working in non-manual occupations to
      19% in women working in manual jobs. Women were more likely to report poor mental
      health status than men, although sex differences were greater among manual
      workers (aOR = 2.26; 95%CI, 1.68-3.05 for women compared to men in the same
      group). Differences according to qualifications were found among women only (aOR
      = 1.58 [95%CI, 1.22-2.05] for women working in manual jobs compared to those
      working in non-manual jobs), while no differences were found among men according
      to qualifications. Psychosocial risk factors were associated with mental health:
      demand was associated in all groups, autonomy only in non-manual occupations, and
      social support only in the most highly qualified working women. Employment
      conditions such as working a split shift (working day with a long lunch break) or
      having a temporary contract were associated with mental health in manual
      occupations only. CONCLUSIONS: Mental health among the working population is
      related to professional qualifications and gender. Women are at greater risk than
      men, especially those working in manual occupations. Psychosocial occupational
      factors are related to mental health status, showing different patterns depending
      on gender and professional qualifications.

PMID- 15498405
TI  - [Variability in hospital care. Nasosinus surgery in Spain].
AB  - OBJECTIVES: To describe variations in the management of nasosinus disorders among
      the Autonomous Communities and hospitals of Spain. METHODS: We analyzed the
      Minimum Basic Data Set of the public health system from 1998-2000 for the
      diagnoses of nasosinus polyps and chronic sinusitis. We studied the distribution
      by regions of the rate of hospitalizations and of 4 indicators of quality of care
      and efficiency: mean length of stay, percentage of discharges without surgery,
      percentage of functional endoscopic sinus surgery and surgical complications. A
      cluster analysis was performed to classify hospitals according to the values of
      these indicators. RESULTS: We analyzed 13061 discharges from 263 hospitals.
      Marked differences were found in age-adjusted hospitalization rates by regions.
      Cluster analysis classified the centers with more than 10 annual discharges in 3
      categories: a) 32 hospitals in which the 4 quality indicators were above average;
      b) 35 hospitals in which 3 of the indicators were below average, and c) 74
      hospitals in which 2 indicators were above average and 2 indicators were below
      average. CONCLUSIONS: Marked interregional variations were found in
      hospitalization rates, as well as in the characteristics of management of
      nasosinus disorders in Spanish hospitals. The centers examined could be grouped
      into three clearly defined patterns according to indicators of quality of care
      and efficiency.

PMID- 15498406
TI  - [Self-regulation systems to control tobacco advertising. An empirical analysis].
AB  - OBJECTIVE: Against the background of the debate aroused by the tobacco
      advertising ban as a result of Directive 98/43/EC and of the Proposed Directive
      of 5/9/2001, we aimed to evaluate how self-regulation of tobacco advertising
      systems has worked in the last 5 years and to evaluate its effectiveness and
      relevance as a potential tool in public health prevention. METHODS: We performed
      a content and discourse analysis of all advertisements appearing in the Sunday
      supplements of the three weekly newspapers with the widest circulation in Spain
      (El Pais, El Mundo, and ABC) between January 1995 and January 2000 to detect
      infractions of the norms of the self-regulation code of the Spanish Tobacco
      Association (Asociacion Espanola de Tabaco [AET]) regarding: a) the identity of
      models used in advertising; b) direct or indirect claims for the therapeutic
      properties of smoking; c) depiction of cigarettes in advertisements, and d)
      printed warnings on advertisements. RESULTS: We examined 910 banners and 369
      advertisements. Very few advertisements displayed rational arguments on elements
      such as price (13%) or product components (7%). Although the AET's code was
      generally respected, the advertisements displayed a series of subtleties that
      allowed the industry to get around the code: 10 of the 369 advertisements
      reviewed depicted famous people (mainly pilots and artists) and one third of them
      used iconic personages (Joe Camel or Marlboro Man); one advertisement suggested
      the therapeutic properties of tobacco and almost all linked smoking with social
      success and leisure. Although cigarettes were not depicted, 18% of the
      advertisements showed substitutes for cigarettes in various places (12%) and a
      large percentage infringed the code's recommendations on printed warnings.
      CONCLUSIONS: The industry's use of creative subtleties infringing its self
      imposed norms begs the question of how far self-regulation is viable when a
      failure in the system can have serious consequences for public health.

PMID- 15498407
TI  - [Who is against prevention? A map of policy actors favoring smoking in Spain].
AB  - OBJECTIVES: For a comprehensive approach to policies on smoking, the map of
      actors related to tobacco and their political ties needs to be identified. The
      present article constitutes the first attempt at this task in Spain. METHODOLOGY:
      Analysis of the press, industry publications, and interviews with key people.
      Active actors favoring smoking in Spain were identified and classified according
      to their characteristics, the sphere in which they act, and their preferred
      territorial arena. RESULTS: We identified tobacco companies (Altadis and Philip
      Morris dominate the market), tobacco trade organizations (tobacconists), front
      line organizations created by the tobacco industry (The Smokers for Tolerance
      Club), organizations of tobacco growers, and processing companies. Distribution
      to retailers is dominated by Logista, owned by Altadis. Other sectors to take
      into account are vending companies and those manufacturing related products
      (cigarette paper, matches or lighters). The contacts of these actors with the
      public administration are reviewed, notable among which are the role of the
      Commissioner for the Tobacco Market, the Ministry of Agriculture, the Ministry of
      Finance and the Ministry of the Economy. Ties were also found with employers'
      organizations, some political parties, and unions, as well as with other sectors
      with social influence such as the media and advertising sectors. CONCLUSIONS: The
      map of actors favoring smoking in Spain is complex and goes beyond the confines
      of the tobacco industry. Understanding this web is crucial to promoting
      comprehensive prevention policies.

PMID- 15498408
TI  - [Comparison of Spanish gypsy and foreign immigrant maltreated children admitted
      to protection centers].
AB  - OBJECTIVES: To determine whether there are differences between Spanish gypsy and
      foreign immigrant children admitted to protection centers in the characteristics
      of the maltreatment, social and familial factors linked to maltreatment, and
      health status. METHODS: The social and health reports of 83 Spanish gypsy and 105
      foreign immigrant children admitted to protection centers of the Aragonese
      Institute for Social Services (Instituto Aragones de Servicios Sociales [IASS])
      because of maltreatment from January 1994 to December 2003 were reviewed.
      Maltreatment, its types, and warning signs were defined and assessed according to
      the guidelines drawn up by the IASS. The social and familial risk factors
      associated with maltreatment were determined according to national studies.
      Health status was assessed following protocols used by the IASS. A descriptive
      and comparative statistical study was performed. RESULTS: The Spanish gypsy
      children were mostly in the age group of 0-5 years, while foreign immigrants were
      mostly in the age group of 12-17 years. Spanish gypsy children showed a greater
      frequency of physical and emotional neglect and/or abandonment (p < 0.001) and
      were more likely to have families with problems of crime (odds ratio [OR] = 16.5;
      95% confidence interval [95%CI], 6.7-40.7), drug/alcohol abuse (OR = 8.8; 95%CI,
      3.7-21) and families with more than one social and health risk factor (OR = 9.3;
      95%CI, 3.8-22.8). Spanish gypsy children showed a greater frequency of
      neurological disorders, disabling diseases, absent or incomplete immunizations,
      and dermatologic diseases. Foreign immigrant children showed a greater frequency
      of physical and psychological and/or sexual abuse (p < 0.001) and were more
      likely to live in a single parent family (OR = 7.9; 95%CI, 2.2-27.7).
      CONCLUSIONS: Identifying the differences between these two groups of maltreated
      children could be useful for professionals working in the community social
      services in charge of developing intervention strategies for the prevention and
      early detection of maltreatment, as well as for professionals in charge of the
      health of these children during their stay in a protection center.

PMID- 15498409
TI  - [Characteristics of road accident victims with positive blood alcohol levels].
AB  - OBJECTIVE: To identify the differential features of positive blood alcohol level
      (BAL) in people injured in road crashes who were attended an acute care service.
      METHODS: Cross-sectional study of persons aged 18 years old or older injured in
      motor vehicle crashes who were attended in the Traumatology Emergency Department
      of Vall d'Hebron Hospital (Spain) between July 2001 and February 2002. RESULTS:
      The study sample included 431 patients. A positive alcohol test was found in
      13.7% of the sample. A statistically significant and independent association was
      found between positive BAL and male sex (odds ratio [OR] = 2.5 [95% CI, 1.3
      5.4]), hospital admission (OR = 2.7 [95% CI, 1.3-5.4]), being attended on a
      weekend (OR = 3.7 [95% CI, 2.0-6.9]) and being attended during the night and
      early morning (OR = 4.6 [95% CI, 2.0-10.3]) or in the morning (OR = 3.6 [95% CI,
      1.5-8.4]). CONCLUSIONS: The present study identifies a subgroup of people injured
      in motor vehicle crashes with a greater likelihood of positive BAL, in whom more
      active screening and secondary prevention activities should be implemented within
      traumatology and acute care settings.

PMID- 15498410
TI  - [Survival analysis with competing risks: estimating failure probability].
AB  - OBJECTIVE: To show the impact of competing risks of death on survival analysis.
      METHOD: We provide an example of survival time without chronic rejection after
      heart transplantation, where death before rejection acts as a competing risk.
      Using a computer simulation, we compare the Kaplan-Meier estimator and the
      multiple decrement model. RESULTS: The Kaplan-Meier method overestimated the
      probability of rejection. Next, we illustrate the use of the multiple decrement
      model to analyze secondary end points (in our example: death after rejection).
      Finally, we discuss Kaplan-Meier assumptions and why they fail in the presence of
      competing risks. CONCLUSIONS: Survival analysis should be adjusted for competing
      risks of death to avoid overestimation of the risk of rejection produced with the
      Kaplan-Meier method.

PMID- 15498411
TI  - [The introduction of technologies in health care systems: from saying to doing].
AB  - INTRODUCTION: Health technology assessment (HTA) is a tool based on scientific
      evidence useful for making decisions about the introduction of technological
      advances in healthcare systems. However, there are multiple elements that
      influence the actual use of the results of HTA. These elements are related both
      to the characteristics of HTA and to the stakeholders involved -health
      professionals, politicians, and society. The aim of this article was to describe
      the main elements that influence the applicability of HTA in practice, as well as
      the use of HTA in clinical practice and health policy. METHODS: A literature
      search was performed in PubMed. The references retrieved, as well as additional
      bibliography and gray literature dealing with different aspects of HTA practice
      identified from the references retrieved, were reviewed. The results are
      presented descriptively, with analysis of the studies grouped according to the
      various HTA-related topics. RESULTS: Key elements that could be improved are
      standardization of the evaluation process, description of the organization's
      mission, prioritization of the technologies to be assessed, the clarity of the
      presentation of results, inclusion of values other than scientific evidence, such
      as social and cost-effectiveness values, and increased international
      coordination. CONCLUSIONS: For many people, the rationale for HTA is its explicit
      role in decision making, despite its problems. The immediate future of HTA would
      seem to include making the assessment process explicit, and the inclusion of HTA
      in decision making. This entails prioritization of technologies, setting limits
      on resource allocation and interrelation with political processes.

PMID- 15498412
TI  - [Use of antihypertensive agents in Cantabria, Spain [1995-2002]: discrepancy with
      the published evidence].
AB  - OBJECTIVE: To ascertain the pattern of prescription of antihypertensive drugs in
      Cantabria and its variation from published evidence between 1995 and 2002.
      METHOD: We reviewed the database of the pharmaceutical data processing system of
      the Cantabrian Health Service on the consumption and cost of the drugs indicated
      in the treatment of hypertension. Consumption data is expressed in defined daily
      doses per thousand inhabitants and day (DID). RESULTS: Consumption of
      antihypertensive agents was 130.2 DID in 1995 and was 235 DID in 2002. The
      contribution of diuretics to overall consumption fell from 34.3% in 1995 to 25.8%
      in 2002, and that of beta-blockers fell from 6.5% in 1995 to 5.9% in 2002. The
      most commonly used group in all years was angiotensin converting-enzyme
      inhibitors, which represented 36.8% of consumption in 2002. Angiotensin-II
      antagonists showed the biggest rise, accounting for 13.2% of prescriptions in
      2002 and for 26% of expenditure on antihypertensive agents. The pattern of use of
      the drugs utilized in the major published trials during this period showed no
      change or even fell, except in the case of enalapril. CONCLUSIONS: The present
      study confirms that the prescription antihypertensive drugs has considerably
      increased and that the consumption pattern of these drugs has changed. The
      discrepancy between these findings and those of the major trials could have
      significant economic implications.

PMID- 15498413
TI  - [Research profiles and appointments to academic posts in preventive medicine and
      public health].

PMID- 15498414
TI  - [Structured triage and urgency relatal case mix analysis. A new management model
      for emergency deparments].

PMID- 15498415
TI  - [Quality of diagnostic test for HIV. Thinking of the patient].

PMID- 15498416
TI  - [Al-baitar].

PMID- 15498438
TI  - [Chronic hepatitis C in HIV co-infected patients. Study of 55 cases with liver
      biopsy].
AB  - BACKGROUND AND OBJECTIVE: To study the evolution of chronic hepatitis in HIV-HCV
      co-infected patients and the factors conditioning this evolution. PATIENTS AND
      METHOD: 55 intravenous drug users with HIV-HCV co-infection were studied. We
      performed a clinical and laboratory study determining the age at the time of HCV
      infection and the date of liver biopsy, HIV stage, CD4 cell count, viral load,
      and time under antiretroviral treatment. Moreover, we analyzed the HCV genotype,
      HCV viral load, ALT plasmatic level, and liver biopsy. Univariate and
      multivariate analyses were made. RESULTS: 55 patients with HIV-HCV co-infection
      were evaluated. In the multivariate analysis, gender (p = 0.034; 95% confidence
      interval [CI], 1.306-1082.625), lowest level of CD4+ lymphocytes (p = 0.021; 95%
      CI, 1,693-653,484) and highest viral load value (p = 0.022; 95% CI, 1366-53,817)
      were significantly correlated with liver disease progression. CONCLUSIONS: Both a
      male sex and a poor immune system situation are associated with a worse evolution
      of chronic hepatitis C.

PMID- 15498439
TI  - [Secular growth changes. Weight, height and body mass index values in infant,
      children, adolescent and young adults from Barcelona population].
AB  - BACKGROUND AND OBJECTIVE: A secular trend in growth has been reported in
      developed countries. Our aim was to evaluate weight, height and body mass index
      values in a middle class sample of people from Barcelona and compare these values
      with those obtained before 1987. SUBJECTS AND METHOD: Height, weight and body
      mass index were evaluated in a) 268 male and 243 female newborns from normal
      gestations of 40 weeks, born in 2001 and 2002; b) 158 boys and 146 girls born
      during 1998-2000 and evaluated every 0.25-0.50 years from 0.25 to 3 years of age;
      c) 2,781 boys and 2,476 girls, aged 3-18 years, evaluated in 2002 and 2003, and
      distributed in 0.5 year intervals, and d) 394 males and 364 females, aged 18-24
      years, evaluated in 2002 and 2003. RESULTS: Mean, standard deviation and
      percentiles values with 0.25-0.5 year-period intervals from birth to adulthood
      are reported. In comparison with data obtained before 1987 in Spanish
      populations, an increase of 3.5 cm was observed in adult height in both sexes as
      well as an increase of 7-8.3 kg in percentiles 3, 50 and 97 values in male adult
      weight with no significant differences in female adult weight. Moreover, pubertal
      growth spurt begins one year earlier in both boys and girls. Age of menarche
      (12.78 [1.30] years) was similar in our adult female population and in the female
      population evaluated before 1987. CONCLUSIONS: A secular trend in growth was
      observed in our population. There is a need to update periodically the growth
      data used in the evaluation of children and adolescents.

PMID- 15498440
TI  - [GHBP, IGF-1 and IGFBP-3 serum levels in familial short-statured and normal
      statured children].
AB  - BACKGROUND AND OBJECTIVE: Growth hormone binding protein (GHBP), insuline-like
      growth factor 1 (IGF-1) and insuline-like growth factor binding protein 3 (IGFBP
      3) serum concentrations were studied in familial short-statured patients (FSS)
      and age-matched normal-statured subjects. The aim of the study was to ascertain
      whether differences in growth factors concentrations between groups could be
      shown and whether they may contribute to explaining the different patterns of
      growth in both groups. SUBJECTS AND METHOD: Serum samples of 38 FSS patients (20
      boys) and 31 normal-statured subjects (15 boys) in Tanner I stage (prepubertal),
      were analysed in a central laboratory. All auxological parameters (height, growth
      velocity, target height, body mass index (BMI) and biochemical parameters (IGF-1
      and IGFBP-3) were standardised for age and sex-matched subjects. GHBP values were
      expressed as percentage of specific binding. RESULTS: The studied populations
      were similar and no statistically-significant differences in chronological age,
      bone age and BMI were found. Height, growth velocity and target height were
      significantly lower in FSS patients compared with normal subjects (p < 0.0001).
      IGF-1, IGFBP-3 and GHBP concentrations were significantly lower in the FSS group
      (p < 0.01). Correlations were found between IGF-1 and IGFBP-3 (r = 0.56; p =
      0.0004) and between IGF-1 and GHBP (r = 0.34; p = 0.03) in the FSS group.
      However, in the normal-statured group only BMI and GHBP were correlated (r = 0.5;
      p = 0.02). CONCLUSIONS: These results strongly support the importance of the
      GH/IGF-1 functional axis in the pattern of growth and probably contribute to
      understanding of the pathophysiologic basis of the auxological differences found
      between groups.

PMID- 15498441
TI  - [Clinical and biochemical characteristics of familial ligand-defective apo B-100
      in a South European population].
AB  - BACKGROUND AND OBJECTIVE: To compare the lipoprotein phenotype between FDB and
      heterozygous familial hypercholesterolemia (FH); to study the prevalence and
      possible founder effect of familial ligand-defective apo B100 (FDB) in a
      Mediterranean population, and to analyze the clinical and biochemical
      characteristics of FDB patients. SUBJECTS AND METHOD: We studied 19 heterozygous
      FDB subjects (8 males) from 12 related families, carriers of the R3500Q mutation
      on the apo B gene, and 57 heterozygous FH (24 males) genetically characterized,
      randomly selected from a total of 213 FH. The genetic diagnosis was established
      with Southern blot analysis, PCR-SSCP analysis and automatic sequencing. In all
      subjects, plasma lipids and apolipoprotein levels were determined with standard
      procedures. RESULTS: We demonstrated a founder effect for the R3500Q mutation in
      a geographically isolated rural area from our community. The prevalence of FDB in
      this area is high: 4/350. Heterozygous FDB subjects showed a statistical
      significantly lower prevalence of xanthomas and coronary heart disease, plasma
      concentrations of total and LDL cholesterol, HDL cholesterol, apo B and apo A-I
      values than heterozygous FH subjects. CONCLUSIONS: A founder effect for the
      R3500Q mutation was found in a rural population with a high prevalence of FDB. In
      our population, FDB patients showed a mild clinical expression and lipoprotein
      phenotype compared with FH patients.

PMID- 15498442
TI  - [The era of antiretroviral therapy... and the era of hepatitis C virus
      coinfection].

PMID- 15498443
TI  - [Update on the human skeletal growth and its markers].

PMID- 15498444
TI  - [Clinical and immunological features in 112 patients with antiphospholipid
      syndrome].
AB  - BACKGROUND AND OBJECTIVE: We decided to describe the demographic, clinical and
      laboratory characteristics of a series of patients with antiphospholipid syndrome
      (APS) (Harris criteria) and review other Spanish published series. PATIENTS AND
      METHOD: We describe 112 patients with APS, 50 primary (PAPS) and 62 secondary
      (SAPS) -56 (90%) to systemic lupus erythematosus (SLE)-, monitorized in two
      referral centers in Malaga (Spain) from 1989 to 2000. All data were obtained from
      the medical records by means of a protocol. RESULTS: The age was similar in both
      groups (42.3 [14.7] years for the whole series). Patients with SAPS had an
      earlier onset of the disease (29.6 [12.6] years, vs 37.0 [13.9] years in PAPS)
      and they had a longer evolution of the disease (143.3 [115.5] months, vs 83.5
      [73.5] months in PAPS). There was a female predominance (84% and 60% in SAPS and
      PAPS, respectively). The prevalences of arterial (43%) and venous thrombosis
      (39%), fetal loss (40%), premature births (9%), anticardiolipin antibodies (88%)
      and lupus anticoagulant (54%) were similar in both groups. The prevalence of ANA
      IFI, thrombocytopenia and autoimmune anemia was higher in SAPS. CONCLUSIONS:
      Patients with PAPS and SAPS did not present any differences in the clinical
      manifestations and immunological disorders of the syndrome. Those patients with
      SAPS were younger at the beginning of the disease and there was a female
      predominance. Our patients were different from those included in other Spanish
      published series, which could be explained by selection and classification bias.

PMID- 15498445
TI  - [Kikuchi-Fujimoto disease].

PMID- 15498447
TI  - [Short stay units, creating the scientific basis].

PMID- 15498449
TI  - [Sarcoidosis, Lofgren's syndrome and uveoparotid fever].

PMID- 15498450
TI  - [Phencyclidine: drug of abuse in Spain?].

PMID- 15498452
TI  - The genomics of gene expression.
AB  - The study of gene regulation on a genomic scale has been constrained by the
      modest pace with which new trans-regulatory factors have been identified and by
      the fact that cis-regulatory sequences have to date been described even in part
      for only a small fraction of vertebrate genes. An indirect approach for assessing
      the significance of cis- and trans-regulatory mechanisms on a global scale is to
      utilize gene expression as a surrogate for transcriptional regulation and to
      combine genome-scale transcriptional profiling with studies of genetic variation,
      classical genetic techniques such as linkage analysis, and examination of allelic
      expression patterns that reveal cis-regulatory variability. A number of recent
      studies employing these methods provide insight into questions of central
      importance to our understanding of the larger role of transcriptional regulation
      in the organization of the human and other complex genomes.

PMID- 15498453
TI  - The evolutionary history of human chromosome 7.
AB  - We report on a comparative molecular cytogenetic and in silico study on
      evolutionary changes in human chromosome 7 homologs in all major primate
      lineages. The ancestral mammalian homologs comprise two chromosomes (7a and
      7b/16p) and are conserved in carnivores. The subchromosomal organization of the
      ancestral primate segment 7a shared by a lemur and higher Old World monkeys is
      the result of a paracentric inversion. The ancestral higher primate chromosome
      form was then derived by a fission of 7b/16p, followed by a centric fusion of
      7a/7b as observed in the orangutan. In hominoids two further inversions with four
      distinct breakpoints were described in detail: the pericentric inversion in the
      human/African ape ancestor and the paracentric inversion in the common ancestor
      of human and chimpanzee. FISH analysis employing BAC probes confined the 7p22.1
      breakpoint of the pericentric inversion to 6.8 Mb on the human reference sequence
      map and the 7q22.1 breakpoint to 97.1 Mb. For the paracentric inversion the
      breakpoints were found in 7q11.23 between 76.1 and 76.3 Mb and in 7q22.1 at 101.9
      Mb. All four breakpoints were flanked by large segmental duplications.
      Hybridization patterns of breakpoint-flanking BACs and the distribution of
      duplicons suggest their presence before the origin of both inversions. We propose
      a scenario by which segmental duplications may have been the cause rather than
      the result of these chromosome rearrangements.

PMID- 15498454
TI  - Organization and concerted evolution of the ampliconic Y-chromosomal TSPY genes
      from cattle.
AB  - The Y-chromosomal gene TSPY (testis-specific protein Y-encoded) is probably
      involved in early spermatogenesis and has a variable copy number in different
      mammalian species. Analysis of bovine BAC clones leads to an estimate of 90 TSPY
      loci on the bovine Y chromosome. Half of these loci (TSPY-M1 and TSPY-M2) contain
      a single copy, while the other loci (TSPY-C) contain a cluster of three, possibly
      four, truncated pseudogenes. Fluorescence in situ hybridization indicated that
      the TSPY loci are located mainly on the short arm (Yp). The TSPY genes appear to
      account for about 2.5% of the Y chromosome and contain several published bovine Y
      chromosomal microsatellites. The homology of TSPY and the major Y-chromosomal
      repetitive elements BRY.2 from cattle and OY.1 from sheep (80-85% similarity)
      further illustrates how the Y chromosome is shaped by rearrangements and
      horizontal spreading of the most abundant sequences. A comparison of TSPY-M1
      sequences from different BAC clones and from related bovine species suggests
      concerted evolution as one of the mechanisms of the rapid evolution of the
      mammalian Y chromosome.

PMID- 15498455
TI  - Complementation of replication origin function in mouse embryonic stem cells by
      human DNA sequences.
AB  - A functional origin of replication was mapped to the transcriptional promoter and
      exon 1 of the hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene in the
      mouse and human genomes. This origin was lost in mouse embryonic stem (ES) cells
      with a spontaneous deletion (approximately 36 kb) at the 5' end of the HPRT
      locus. Restoration of HPRT activity by homologous recombination with human/mouse
      chimeric sequences reconstituted replication origin activity in two independent
      ES cell lines. Quantitative PCR analyses of abundance of genetic markers in size
      fractionated nascent DNA indicated that initiation of DNA replication coincided
      with the site of insertion in the mouse genome of the 335 bp of human DNA
      containing the HPRT exon 1 and a truncated promoter. The genetic information
      contained in the human sequence and surrounding mouse DNA was analyzed for cis
      acting elements that might contribute to selection and functional activation of a
      mammalian origin of DNA replication.

PMID- 15498456
TI  - Gene expression profiles of apoptotic neurons.
AB  - The multigenic program underlying neuronal apoptosis is mostly unknown. To study
      the program, we used genome-scale screening by oligonucleotide microarrays during
      serum and potassium deprivation-induced apoptosis of cerebellar granule neurons.
      From the 8740 genes interrogated by the arrays, 423 genes were found to be
      regulated at both the transcriptional and the posttranscriptional level and
      segregated into distinct clusters. Semantic clustering based on gene ontologies
      showed coordinated expression of genes with common biological functions and
      metabolic pathways. Among the genes implicated in apoptotic cerebellar granule
      neurons, 70 were in common with those differentially expressed in cortical
      neurons exposed to amyloid beta-protein, indicating the existence of common
      mechanisms responsible for neuronal cell death. Our results offer a genomic view
      of the changes that accompany neuronal apoptosis and yield new insights into the
      underlying molecular basis.

PMID- 15498457
TI  - New insights into ADPKD molecular pathways using combination of SAGE and
      microarray technologies.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in
      the PKD1 or PKD2 gene, but cellular mechanisms of cystogenesis remain unclear. In
      an attempt to display the array of cyst-specific molecules and to elucidate the
      disease pathway, we have performed comprehensive high-throughput expression
      analysis of normal and ADPKD epithelia in a two-step fashion. First, we generated
      expression profiles of normal and cystic epithelia derived from kidney and liver
      using serial analysis of gene expression (SAGE). We found 472 and 499
      differentially expressed genes with fivefold difference in liver and kidney
      libraries, respectively. These genes encode growth factors, transcription
      factors, proteases, apoptotic factors, molecules involved in cell-extracellular
      matrix interactions, and ion channels. As a second step, we constructed a custom
      cDNA microarray using a subset of the differentially regulated genes identified
      by SAGE and interrogated ADPKD patient samples. Subsequently, a set of
      differentially expressed genes was refined to 26 up-regulated and 48 down
      regulated genes with ap value of <0.01. This study may provide valuable insights
      into the pathophysiology of ADPKD and suggest potential therapeutic targets.

PMID- 15498458
TI  - Phylogenetic footprinting reveals extensive conservation of Sonic Hedgehog (SHH)
      regulatory elements.
AB  - Sonic Hedgehog (SHH) plays a fundamental role in numerous developmental processes
      including morphogenesis of limbs, nervous system, and teeth. Using a Bayesian
      alignment algorithm for phylogenetic footprinting we analyzed approximately 28 kb
      of noncoding DNA in the SHH locus of human and mouse. This showed that the length
      of conserved noncoding sequences (4196 nt) shared by these species was
      approximately 3 times larger than the SHH coding sequence (1386 nt). Most
      segments were located in introns (53%) or within 2-kb regions upstream (16%) or
      downstream (20%) of the first and last SHH codon. Even though regions more than 2
      kb upstream or downstream of the first and last SHH codon represented 57% (16 kb)
      of the sequence compared, they accounted for only 11% (494 nt) of the total
      length of conserved noncoding segments. One region of 650 nt downstream of SHH
      was identified as a putative scaffold/matrix attachment region (SMAR). Human
      mouse analysis was complemented by sequencing in apes, monkeys, rodents, and
      bats, thus further confirming the evolutionary conservation of some segments. Gel
      shift assays indicated that conserved segments are targeted by nuclear proteins
      and showed differences between two cell types that expressed different levels of
      SHH, namely human endothelial cells and breast cancer cells. The relevance of
      these findings with respect to regulation of SHH expression during normal and
      pathologic development is discussed.

PMID- 15498459
TI  - First comprehensive mapping of cartilage transcripts to the human genome.
AB  - We present the first comprehensive transcriptome-to-genome mapping for human
      cartilage. First, we determined that the cartilage transcriptome represents
      between 13,200 and 15,800 unique genes. Next, a subset of approximately 10,000 of
      the best characterized cartilage-expressed transcripts (CETs) was selected and
      mapped to the human genome. The distribution of CETs across the genome was found
      to be significantly different compared to the expected distribution. Furthermore,
      clusters of adjacent coordinately transcribed genes, as well as numerous "hot
      spots" and "cold spots" for transcription in cartilage, were identified. We
      propose that transcriptional control in cartilage can be exerted over genomic
      domains containing as few as four neighboring genes. Our findings, which are
      consistent with recent "chromatin domain" models of transcription, are further
      supported by our identification of CETs that putatively encode components of the
      HDAC- and Swi/SNF-mediated chromatin remodeling pathways. Our study illustrates
      the value of comprehensive high-resolution scans to detect transcription patterns
      within the human genome.

PMID- 15498460
TI  - Analysis of the human VPS13 gene family.
AB  - The gene mutated in chorea-acanthocytosis (CHAC; approved gene symbol VPS13A)
      encodes chorein, a protein similar to yeast Vps13p. We detected several similar
      putative human proteins by BLAST analysis of chorein. We characterized the
      structure of three new genes encoding these CHAC-similar proteins, located on
      chromosomes 1p36, 8q22, and 15q21. The most similar gene in yeast to all four
      human genes is Vps13, and therefore the human genes were named VPS13A (CHAC,
      9q21), VPS13B (8q22), VPS13C (15q21), and VPS13D (1p36). VPS13B has recently been
      reported as COH1, altered in Cohen syndrome. For each gene, we describe several
      alternative splicing variants; at least two transcripts per gene are major forms.
      The expression pattern of these genes is ubiquitous, with some tissue-specific
      differences between several transcript variants. Protein sequence comparisons
      suggest that intramolecular duplications have played an important role in the
      evolution of this gene family.

PMID- 15498461
TI  - Chromosome-specific microsatellite multiplex sets for linkage studies in the
      domestic dog.
AB  - To expedite linkage studies and positional cloning efforts in the dog, Minimal
      Screening Set 2 (MSS-2) of 327 canine microsatellite markers has been multiplexed
      into chromosome-specific panels. MSS-2 provides 9 Mb coverage of the canine
      genome with no gaps larger than 17.1 Mb and is the most recent and comprehensive
      set of microsatellites available for whole-genome scans. Markers were labeled
      with fluorescent dyes based on locations and expected product sizes to facilitate
      the multiplexing of a maximum number of markers for each chromosome. All markers
      are amplified using a single thermal cycling program and PCR mix and are
      optimized for resolution on an ABI 3100 genetic analyzer. Sixty-nine chromosome
      specific panels were created by coamplification of a maximum number of markers
      and subsequent coloading of the remaining markers.

PMID- 15498462
TI  - Targeted point mutagenesis of mouse Kcnq1: phenotypic analysis of mice with point
      mutations that cause Romano-Ward syndrome in humans.
AB  - Inherited long QT syndrome is most frequently associated with mutations in KCNQ1,
      which encodes the primary subunit of a potassium channel. Patients with mutations
      in KCNQ1 may show only the cardiac defect (Romano-Ward syndrome or RWS) or may
      also have severe deafness (Jervell and Lange-Nielsen syndrome or JLNS). Targeted
      disruption of mouse Kcnq1 models JLNS in that mice are deaf and show abnormal
      ECGs. However, the phenotype is broader than that seen in patients. Most
      dramatically, the inner ear defects result in a severe hyperactivity/circling
      behavior, which may influence cardiac function. To understand the etiology of the
      cardiac phenotype in these mice and to generate a potentially more useful model
      system, we generated new mouse lines by introducing point mutations associated
      with RWS. The A340E line phenocopies RWS: the repolarization phenotype is
      inherited in a dominant manner and is observed independent of any inner ear
      defect. The T311I line phenocopies JLNS, with deafness associated with inner hair
      cell malfunction.

PMID- 15498463
TI  - The human LMX1B gene: transcription unit, promoter, and pathogenic mutations.
AB  - LMX1B is a LIM-homeodomain transcription factor required for the normal
      development of dorsal limb structures, the glomerular basement membrane, the
      anterior segment of the eye, and dopaminergic and serotonergic neurons.
      Heterozygous loss-of-function mutations in LMX1B cause nail patella syndrome
      (NPS). To further understand LMX1B gene regulation and to identify pathogenic
      mutations within the coding region, a detailed analysis of LMX1B gene structure
      was undertaken. 5' -RACE and primer extension identified a long 5' -untranslated
      region of 1.3 kb that contains two upstream open-reading frames (uORFs).
      Transient transfection assays showed that sequences required for basal promoter
      activity extend no further than 112 bp upstream. An additional 47 mutations have
      been identified in the coding region, as well as nine deletions of large portions
      of the gene, but not in the promoter or highly conserved intronic sequences. The
      range of mutations and the identification of uORFs suggest further complexity in
      the regulation of LMX1B expression.

PMID- 15498465
TI  - Caspase-1zeta, a new splice variant of the caspase-1 gene.
AB  - Five alternatively spliced mRNA isoforms of human caspase-1 have been identified
      previously and we report here the cloning of a new isoform, named CASP1 zeta
      (zeta), from human ovarian surface epithelial cell cDNA. The new isoform zeta is
      identical to the alpha isoform but missing 79 nucleotides in the coding region of
      the prodomain of procaspase-1. Analysis of the cDNA sequence of the zeta isoform
      revealed an ORF of a shorter protein missing the 39 amino acids at the amino
      terminal of procaspase-1alpha, which comprises the important caspase activating
      recruitment domain (CARD), which is required for interactions between caspases
      and other proteins. Secondary structure analysis of procaspase-1 CARD predicted
      the truncation of the alpha1, the alpha2, and part of the alpha3 helix in the
      zeta isoform in comparison to the full-length alpha isoform. The new zeta isoform
      was expressed in many, but not all, adult human tissues by RT-PCR. In HEK293
      cells, transient overexpression of wild-type caspase-1zeta induced apoptosis to
      levels similar to those of caspase-1alpha. However, mutational change at the
      caspase-1 active center of the Cys 246 of caspase-1zeta, as well as Cys 285 of
      caspase-1alpha, completely abolished their apoptotic activity. Our findings
      suggest that caspase-1zeta is a widespread, new proapoptotic isoform of caspase
      1. They also demonstrate that the first 39 amino acids of the N-terminal of the
      CARD in procaspase-1 are not required for its apoptotic activity.

PMID- 15498464
TI  - Cloning, genomic structure, and expression profiles of TULIP1 (GARNL1), a brain
      expressed candidate gene for 14q13-linked neurological phenotypes, and its murine
      homologue.
AB  - Previously, we have described the clinical and molecular characterization of a de
      novo 14q13.1-q21.1 microdeletion, less than 3.5 Mb in size, in a patient with
      severe microcephaly, psychomotor retardation, and other clinical anomalies. Here
      we report the characterization of the genomic structure of the human tuberin-like
      protein gene 1 (TULIP1; approved gene symbol GARNL1), a CpGisland-associated,
      brain-expressed candidate gene for the neurological findings in our patient, and
      its murine homologue. The human TULIP1 gene was mapped to chromosome band 14q13.2
      by fluorescence in situ hybridization of BAC clone RP11-355C3 (GenBank Accession
      No. AL160231), containing the 3' region of the gene. TULIP1 spans about 271 kb of
      human genomic DNA and is divided into 41 exons. An untranscribed, processed
      pseudogene of TULIP1 was found on human chromosome band 9q31.1. The active locus
      TULIP1, encoding a predicted protein of 2036 amino acids, is expressed
      ubiquitously in pre- and postnatal human tissues. The murine homologue Tulip1
      spans about 220 kb of mouse genomic DNA and is also divided into 41 exons,
      encoding a predicted protein of 2035 amino acids. No pseudogene could be found in
      the available mouse sequence data. Several splicing variants were found.
      Considering the location, expression profile, and predicted function, TULIP1 is a
      strong candidate for several neurological features seen in 14q deletion patients.
      Additionally we searched for mutations in the coding region of TULIP1 in subjects
      from a family with idiopathic basal ganglia calcification (IBGC; Fahr disease),
      previously linked to chromosome 14q. We identified two novel SNPs in the intron
      exon boundaries; however, they did not segregate only with affected subjects in
      the predicted model of an autosomal dominant disease such as IBGC.

PMID- 15498466
TI  - Bidirectional transcriptional activity of the Pgk1 promoter and transmission
      ratio distortion in Capn3-deficient mice.
AB  - A calpain 3 (Capn3) deficiency model was created by targeted disruption of the
      mouse Capn3 gene through homologous recombination in ES cells. Analysis of the
      genotype of pups from heterozygous crosses revealed a transmission ratio
      distortion (TRD) in favor of homozygous Capn3-deficient mice. This TRD was not
      observed in a second model of Capn3 deficiency, ruling out a possible involvement
      of Capn3 deficiency in this phenotype. The molecular nature of the TRD was
      investigated by quantitative RT-PCR and RACE-PCR analyses. We observed the
      presence in testis and ovaries of abundant, novel transcripts of the Capn3 gene
      arising from the antisense strand of the Pgk1-neomycin cassette. Although we
      could not detect corresponding translation products, our results suggest that the
      activity of the Pgk1 promoter could be the causative factor of TRD. This first
      example of TRD induced by an introduced cassette further emphasizes the care that
      should be taken in interpreting phenotypes of animal models, especially when
      dealing with reproductive functions, and further supports the rationale of using
      excisable cassettes in inactivation strategies.

PMID- 15498467
TI  - A rare event of insertion polymorphism of a HERV-K LTR in the human genome.
AB  - Human endogenous retroviruses (HERVs), which constitute a significant part of the
      human genome, might have a serious impact on primate evolution. Over a hundred
      insertions of HERV-K(HML-2) family members distinguish the human genome from
      other primate genomes. However, only three cases of insertion polymorphisms have
      been reported so far, all for endogenous HERV-K proviruses. This suggests that
      some retroviral integrations occurred rather recently in human genome evolution.
      In this report, we describe a very rare case of true insertion polymorphism of a
      solitary HERV-K LTR in the human genome. Distribution of the LTR-containing
      allele was tested in 5 Africans and 83 individuals from three Russian
      populations. The allele frequency appeared to be relatively high in populations
      of both European and Asian origin. The detected polymorphic LTR could be a useful
      molecular genetic marker of the corresponding genomic region.

PMID- 15498468
TI  - ADLAPH: A molecular haplotyping method based on allele-discriminating long-range
      PCR.
AB  - We present a method, called Allele-Discriminating Long and Accurate PCR
      Haplotyping (ADLAPH), for directly determining haplotypes from an extended
      genomic region. This method uses allele-discriminating primers in long-range PCR
      to amplify only one of the two chromosome homologues for the region of interest.
      Haplotypes are then determined from these phase-separated PCR fragments by
      conventional single nucleotide polymorphism (SNP) genotyping methods. This simple
      robust procedure makes it practical for high-throughput haplotyping of unrelated
      individuals, and potentially allows direct observation of haplotype information
      for up to 40 kb or more. We demonstrate the feasibility of this molecular
      haplotyping procedure by generating apolipoprotein E (APOE) haplotypes from 100
      unrelated subjects.

PMID- 15498469
TI  - Direct determination of MUC5B promoter haplotypes based on the method of single
      strand conformation polymorphism and their statistical estimation.
AB  - Haplotype-based human genome research is important in identifying disease
      susceptibility genes efficiently. Although haplotype reconstruction by
      statistical methods is widely used, direct haplotype determination by molecular
      techniques has also been developed as a complementary method for statistical
      estimation. In this study, we demonstrate a molecular haplotyping method making
      use of single-strand conformation polymorphism (SSCP) gels. We identified 10
      common SNPs and a dinucleotide insertion/deletion polymorphism within 2-kb region
      upstream of the transcription initiation site of MUC5B and determined haplotype
      structure, dividing the region into two DNA fragments. Real haplotypes were
      determined unambiguously by our SSCP-based analysis with fragments longer than 1
      kb. Haplotypes reconstructed from diploid genotypes in the same region by the
      statistical methods including EM algorithm were also evaluated. Direct comparison
      between statistical estimation and direct determination of haplotypes revealed
      that major haplotypes containing multiple marker sites showing strong LD are
      estimated in great accuracy but that a variety of haplotypes reflecting weak LD
      are not reconstructed precisely enough. Our data can be helpful in implementing
      molecular haplotyping or statistical estimation, since usage of these methods may
      be determined depending on the haplotype structures.

PMID- 15498470
TI  - Network plan for genome progress.

PMID- 15498471
TI  - London's global bid.

PMID- 15498472
TI  - Many shades of green.

PMID- 15498473
TI  - Chris Somerville.
AB  - Chris Somerville is Director of the Carnegie Institution Department of Plant
      Biology and a professor of Biological Sciences at Stanford University. He grew up
      in the Canadian north and was educated at the University of Alberta. He was one
      of the early Arabidopsis enthusiasts and has used the plant to study a variety of
      topics in cell and molecular biology. He is currently exploring the complexities
      of plant cell wall biogenesis.

PMID- 15498474
TI  - The notochord.

PMID- 15498475
TI  - Human olfactory psychophysics.

PMID- 15498476
TI  - Evolution of gap junctions: the missing link?

PMID- 15498477
TI  - Essential function of nitric oxide synthase in Drosophila.

PMID- 15498478
TI  - tRNA maturation: RNA polymerization without a nucleic acid template.
AB  - The CCA-adding enzyme, which builds and repairs the 3' terminal CCA sequence of
      tRNA, is the only RNA polymerase that can synthesize a defined nucleotide
      sequence without using a nucleic acid template. New cocrystal structures tell us
      how this remarkable enzyme works.

PMID- 15498479
TI  - Auditory neuroscience: a time for coincidence?
AB  - Mammals and birds appear to encode timing differences between the ears, a major
      cue for auditory localization, in fundamentally different ways. It now appears
      that results from different species can be accommodated within a single general
      framework.

PMID- 15498480
TI  - Hedgehog signaling: measuring ligand concentrations with receptor ratios.
AB  - How the binding of Hedgehog to its receptor, Patched, initiates signaling is
      poorly understood. A recent study suggests a mechanism by which the ratio of
      unliganded to liganded Patched determines the cellular response.

PMID- 15498481
TI  - Object motion: a world view.
AB  - Moving objects are detected by virtue of their shifting image on the retina. But
      to know how objects are moving in the world, we must take into account the
      rotation of our eyes, as well as the rotation of our head. A recent paper
      describes neurons that carry out this computation.

PMID- 15498482
TI  - Damage signaling: RecQ sends an SOS to you.
AB  - The DNA helicase RecQ is required for proper induction of the SOS response to
      replication stress in Escherichia coli. Unwinding of stalled replication forks by
      RecQ family helicases in bacteria, and possibly in eukaryotes, may provide a
      means of damage signaling and recovering stalled replication forks.

PMID- 15498483
TI  - NF-kappaB signaling: flipping the switch with polyubiquitin chains.
AB  - Protein modification by ubiquitin has emerged as an important cellular regulatory
      mechanism. Recent studies illustrate the surprising ways in which polyubiquitin
      chains are manipulated in the regulation of NF-kappaB signaling.

PMID- 15498484
TI  - Telomere biology: a new player in the end zone.
AB  - Yet another protein has been added to the crowd of players found at the ends of
      chromosomes. Known variously as PTOP, PIP1 or TINT1, this negative regulator of
      telomere length connects some of the key proteins already known to be present -
      TRF1, TIN2, POT1, and TRF2 - and adds even more complexity to telomere protein
      interactions.

PMID- 15498485
TI  - Neuropathology: many paths lead to hereditary spastic paraplegia.
AB  - Studies with animal models are providing new insights into the pathology of
      hereditary spastic paraplegia, particularly how mutations in multiple, converging
      pathways can lead to this family of neuropathies.

PMID- 15498486
TI  - Sorting nexin-1 mediates tubular endosome-to-TGN transport through coincidence
      sensing of high- curvature membranes and 3-phosphoinositides.
AB  - BACKGROUND: Sorting nexins (SNXs) are phox homology (PX) domain-containing
      proteins thought to regulate endosomal sorting of internalized receptors. The
      prototypical SNX is sorting nexin-1 (SNX1), a protein that through its PX domain
      binds phosphatidylinositol 3-monophosphate [PtdIns(3)P] and phosphatidylinositol
      3,5-bisphosphate [PtdIns(3,5)P(2)]. SNX1 is associated with early endosomes, from
      where it has been proposed to regulate the degradation of internalized epidermal
      growth factor (EGF) receptors through modulating endosomal-to-lysosomal sorting.
      RESULTS: We show here that SNX1 contains a BAR (Bin/Amphiphysin/Rvs) domain, a
      membrane binding domain that endows SNX1 with the ability to form dimers and to
      sense membrane curvature. We present evidence that through coincidence detection,
      the BAR and PX domains efficiently target SNX1 to a microdomain of the early
      endosome defined by high curvature and the presence of 3-phosphoinositides. In
      addition, we show that the BAR domain endows SNX1 with an ability to tubulate
      membranes in-vitro and drive the tubulation of the endosomal compartment in-vivo.
      Using RNA interference (RNAi), we establish that SNX1 does not play a role in EGF
      or transferrin receptor sorting; rather it specifically perturbs endosome-to
      trans Golgi network (TGN) transport of the cation-independent mannose-6-phosphate
      receptor (CI-MPR). Our data support an evolutionarily conserved function for SNX1
      from yeast to mammals and provide functional insight into the molecular
      mechanisms underlying lipid-mediated protein targeting and tubular-based protein
      sorting. CONCLUSIONS: We conclude that through coincidence detection SNX1
      associates with a microdomain of the early endosome-characterized by high
      membrane curvature and the presence of 3-phosphoinositides-from where it
      regulates tubular-based endosome-to-TGN retrieval of the CI-MPR.

PMID- 15498487
TI  - XRHAMM functions in ran-dependent microtubule nucleation and pole formation
      during anastral spindle assembly.
AB  - BACKGROUND: The regulated assembly of microtubules is essential for bipolar
      spindle formation. Depending on cell type, microtubules nucleate through two
      different pathways: centrosome-driven or chromatin-driven. The chromatin-driven
      pathway dominates in cells lacking centrosomes. RESULTS: Human RHAMM (receptor
      for hyaluronic-acid-mediated motility) was originally implicated in hyaluronic
      acid-induced motility but has since been shown to associate with centrosomes and
      play a role in astral spindle pole integrity in mitotic systems. We have
      identified the Xenopus ortholog of human RHAMM as a microtubule-associated
      protein that plays a role in focusing spindle poles and is essential for
      efficient microtubule nucleation during spindle assembly without centrosomes.
      XRHAMM associates both with gamma-TuRC, a complex required for microtubule
      nucleation and with TPX2, a protein required for microtubule nucleation and
      spindle pole organization. CONCLUSIONS: XRHAMM facilitates Ran-dependent,
      chromatin-driven nucleation in a process that may require coordinate activation
      of TPX2 and gamma-TuRC.

PMID- 15498488
TI  - SIR2 is required for polycomb silencing and is associated with an E(Z) histone
      methyltransferase complex.
AB  - BACKGROUND: SIR2 was originally identified in S. cerevisiae for its role in
      epigenetic silencing through the creation of specialized chromatin domains. It is
      the most evolutionarily conserved protein deacetylase, with homologs in all
      kingdoms. SIR2 orthologs in multicellular eukaryotes have been implicated in
      lifespan determination and regulation of the activities of transcription factors
      and other proteins. Although SIR2 has not been widely implicated in epigenetic
      silencing outside yeast, Drosophila SIR2 mutations were recently shown to perturb
      position effect variegation, suggesting that the role of SIR2 in epigenetic
      silencing may not be restricted to yeast. RESULTS: Evidence is presented that
      Drosophila SIR2 is also involved in epigenetic silencing by the Polycomb group
      proteins. Sir2 mutations enhance the phenotypes of Polycomb group mutants and
      disrupt silencing of a mini-white reporter transgene mediated by a Polycomb
      response element. Consistent with this, SIR2 is physically associated with
      components of an E(Z) histone methyltransferase complex. SIR2 binds to many
      euchromatic sites on polytene chromosomes and colocalizes with E(Z) at most
      sites. CONCLUSIONS: SIR2 is involved in the epigenetic inheritance of silent
      chromatin states mediated by the Drosophila Polycomb group proteins and is
      physically associated with a complex containing the E(Z) histone
      methyltransferase.

PMID- 15498489
TI  - A Rho GTPase signaling pathway is used reiteratively in epithelial folding and
      potentially selects the outcome of Rho activation.
AB  - A single Rho GTPase family member is capable of initiating several different
      processes, including cell cycle regulation, cytokinesis, cell migration, and
      transcriptional regulation . It is not clear, however, how the Rho protein
      selects which of these processes to initiate. Guanine nucleotide exchange factors
      (GEFs), proteins that activate Rho GTPases, could be important in making this
      selection. We show here that in vivo, DRhoGEF2, a GEF that is ubiquitously
      expressed and specific for Rho1, is reiteratively required for epithelial folding
      and invagination, but not for other processes regulated by Rho. The limitation of
      DRhoGEF2 function supports the hypothesis that the GEF selects the outcome of Rho
      activation. DRhoGEF2 exerts its effects in gastrulation through the regulation of
      Myosin II to orchestrate coordinated apical cell constriction. Apical myosin
      localization is also regulated by Concertina (Cta), a Galpha(12/13) family member
      that is thought to activate DRhoGEF2 and is itself activated by a putative
      ligand, Folded gastrulation (Fog). Fog and Cta also play a role in the
      morphogenetic events requiring DRhoGEF2, suggesting the existence of a conserved
      signaling pathway in which Fog, Cta, and DRhoGEF2 locally activate Myosin for
      epithelial invagination and folding.

PMID- 15498490
TI  - Drosophila RhoGEF2 associates with microtubule plus ends in an EB1-dependent
      manner.
AB  - Members of the Rho/Rac/Cdc42 superfamily of GTPases and their upstream
      activators, guanine nucleotide exchange factors (GEFs) , have emerged as key
      regulators of actin and microtubule dynamics. In their GTP bound form, these
      proteins interact with downstream effector molecules that alter actin and
      microtubule behavior. During Drosophila embryogenesis, a Galpha subunit
      (Concertina) and a Rho-type guanine nucleotide exchange factor (DRhoGEF2) have
      been implicated in the dramatic epithelial-cell shape changes that occur during
      gastrulation and morphogenesis . Using Drosophila S2 cells as a model system, we
      show that DRhoGEF2 induces contractile cell shape changes by stimulating myosin
      II via the Rho1 pathway. Unexpectedly, we found that DRhoGEF2 travels to the cell
      cortex on the tips of growing microtubules by interaction with the microtubule
      plus-end tracking protein EB1. The upstream activator Concertina, in its GTP but
      not GDP bound form, dissociates DRhoGEF2 from microtubule tips and also causes
      cellular contraction. We propose that DRhoGEF2 uses microtubule dynamics to
      search for cortical subdomains of receptor-mediated Galpha activation, which in
      turn causes localized actomyosin contraction associated with morphogenetic
      movements during development.

PMID- 15498491
TI  - Endocytosis controls spreading and effective signaling range of Fgf8 protein.
AB  - Secreted signaling molecules released from a restricted source are of great
      importance during embryonic development because they elicit induction,
      proliferation, differentiation, and patterning events in target cells . Fgf8 is a
      member of the fibroblast growth factor family with key inductive functions during
      vertebrate development of, for example, the forebrain , midbrain , cerebellum ,
      heart , inner ear , and mesoderm . However, the mechanism by which the signaling
      range of Fgf8 is controlled in a field of target cells is unknown. We studied
      Fgf8 as a potential morphogen in the nascent neuroectoderm of living zebrafish
      embryos. We find that spreading of epitope-tagged Fgf8 through target tissue is
      carefully controlled by endocytosis and subsequent degradation in lysosomes, or
      "restrictive clearance," from extracellular spaces. If internalization is
      inhibited, Fgf8 protein accumulates extracellularly, spreads further, and
      activates target gene expression over a greater distance. Conversely, enhanced
      internalization increases Fgf8 uptake and shortens its effective signaling range.
      Our results suggest that Fgf8 spreads extracellularly by a diffusion-based
      mechanism and demonstrate that target cells can actively influence, through
      endocytosis and subsequent degradation, the availability of Fgf8 ligand to other
      target cells.

PMID- 15498492
TI  - Nonvisual responses to light exposure in the human brain during the circadian
      night.
AB  - The brain processes light information to visually represent the environment but
      also to detect changes in ambient light level. The latter information induces non
      image-forming responses and exerts powerful effects on physiology such as
      synchronization of the circadian clock and suppression of melatonin. In rodents,
      irradiance information is transduced from a discrete subset of photosensitive
      retinal ganglion cells via the retinohypothalamic tract to various hypothalamic
      and brainstem regulatory structures including the hypothalamic suprachiasmatic
      nuclei, the master circadian pacemaker. In humans, light also acutely modulates
      alertness, but the cerebral correlates of this effect are unknown. We assessed
      regional cerebral blood flow in 13 subjects attending to auditory and visual
      stimuli in near darkness following light exposures (>8000 lux) of different
      durations (0.5, 17, 16.5, and 0 min) during the biological night. The bright
      broadband polychromatic light suppressed melatonin and enhanced alertness.
      Functional imaging revealed that a large-scale occipito-parietal attention
      network, including the right intraparietal sulcus, was more active in proportion
      to the duration of light exposures preceding the scans. Activity in the
      hypothalamus decreased in proportion to previous illumination. These findings
      have important implications for understanding the effects of light on human
      behavior.

PMID- 15498493
TI  - Mechanisms regulating SHORT-ROOT intercellular movement.
AB  - Signaling centers within developing organs regulate morphogenesis in both plants
      and animals. The putative transcription factor SHORT-ROOT (SHR) is an organizing
      signal regulating the division of specific stem cells in the Arabidopsis root.
      Comparison of gene transcription with protein localization indicates that SHR
      moves in a highly specific manner from the cells of the stele in which it is
      synthesized outward. Here, we provide evidence that SHR intercellular trafficking
      is both regulated and targeted. First, we show that subcellular localization of
      SHR in the stele is intrinsic to the SHR protein. Next, we show that SHR must be
      present in the cytoplasm to move, providing evidence that SHR movement is
      regulated. Finally, we describe an informative new shr allele, in which the
      protein is present in the cytoplasm yet does not move. Thus, in contrast to
      proteins that move by a process resembling diffusion, a cytoplasmic pool of SHR
      is not sufficient for movement.

PMID- 15498494
TI  - A nucleolar isoform of the Fbw7 ubiquitin ligase regulates c-Myc and cell size.
AB  - The human tumor suppressor Fbw7/hCdc4 functions as a phosphoepitope-specific
      substrate recognition component of SCF ubiquitin ligases that catalyzes the
      ubiquitination of cyclin E , Notch , c-Jun and c-Myc . Fbw7 loss in cancer may
      thus have profound effects on the pathways that govern cell division,
      differentiation, apoptosis, and cell growth. Fbw7-inactivating mutations occur in
      human tumor cell lines and primary cancers , and Fbw7 loss in cultured cells
      causes genetic instability . In mice, deletion of Fbw7 leads to embryonic
      lethality associated with defective Notch and cyclin E regulation . The human
      Fbw7 locus encodes three protein isoforms (Fbw7alpha, Fbw7beta, and Fbw7gamma) .
      We find that these isoforms occupy discrete subcellular compartments and have
      identified cis-acting localization signals within each isoform. Surprisingly, the
      Fbw7gamma isoform is nucleolar, colocalizes with c-Myc when the proteasome is
      inhibited, and regulates nucleolar c-Myc accumulation. Moreover, we find that
      knockdown of Fbw7 increases cell size consistent with its ability to control c
      Myc levels in the nucleolus. We suggest that interactions between c-Myc and
      Fbw7gamma within the nucleolus regulate c-Myc's growth-promoting function and
      that c-Myc activation is likely to be an important oncogenic consequence of Fbw7
      loss in cancers.

PMID- 15498495
TI  - Ectopic expression of DLK1 protein in skeletal muscle of padumnal heterozygotes
      causes the callipyge phenotype.
AB  - The callipyge (CLPG) phenotype is an inherited skeletal muscle hypertrophy
      described in sheep. It is characterized by an unusual mode of inheritance ("polar
      overdominance") in which only heterozygous individuals having received the CLPG
      mutation from their father (+(MAT)/CLPG(PAT)) express the phenotype .
      +(MAT)/CLPG(PAT) individuals are born normal and develop the muscular hypertrophy
      at approximately 1 month of age. The CLPG mutation was identified as an A to G
      transition in a highly conserved dodecamer motif located between the imprinted
      DLK1 and GTL2 genes . This motif is thought to be part of a long-range control
      element (LRCE) because the CLPG mutation was shown, in postnatal skeletal muscle,
      to enhance the transcript levels of the DLK1, PEG11, GTL2, and MEG8 genes in cis
      without altering their imprinting status . As a result, the +(MAT)/CLPG(PAT)
      individuals have a unique expression profile thought to underlie the callipyge
      phenotype: an overexpression of the paternally expressed protein encoding DLK1
      (Figure 1A) and PEG11 transcripts in the absence of an overexpression of the
      maternally expressed noncoding GTL2 and MEG8 transcripts . However, the way in
      which this distinct expression profile causes the callipyge muscular hypertrophy
      has remained unclear. Herein, we demonstrate that the callipyge phenotype is
      perfectly correlated with ectopic expression of DLK1 protein in hypertrophied
      muscle of +(MAT)/CLPG(PAT) sheep. We demonstrate the causality of this
      association by inducing a generalized muscular hypertrophy in transgenic mice
      that express DLK1 in skeletal muscle. The absence of DLK1 protein in skeletal
      muscle of CLPG/CLPG animals, despite the presence of DLK1 mRNA, supports a trans
      inhibition mediated by noncoding RNAs expressed from the maternal allele.

PMID- 15498496
TI  - The Drosophila fragile X gene negatively regulates neuronal elaboration and
      synaptic differentiation.
AB  - Fragile X Syndrome (FraX) is the most common form of inherited mental
      retardation. The disease is caused by the silencing of the fragile X mental
      retardation 1 (fmr1) gene, which encodes the RNA binding translational regulator
      FMRP . In FraX patients and fmr1 knockout mice, loss of FMRP causes denser and
      morphologically altered postsynaptic dendritic spines . Previously, we
      established a Drosophila FraX model and showed that dFMRP acts as a negative
      translational regulator of Futsch/MAP1B and negatively regulates synaptic
      branching and structural elaboration in the peripheral neuromuscular junction
      (NMJ) . Here, we investigate the role of dFMRP in the central brain, focusing on
      the mushroom body (MB), the learning and memory center . In MB neurons, dFMRP
      bidirectionally regulates multiple levels of structural architecture, including
      process formation from the soma, dendritic elaboration, axonal branching, and
      synaptogenesis. Drosophila fmr1 (dfmr) null mutant neurons display more complex
      architecture, including overgrowth, overbranching, and abnormal synapse
      formation. In contrast, dFMRP overexpression simplifies neuronal structure,
      causing undergrowth, underbranching, and loss of synapse differentiation. Studies
      of ultrastructural dfmr mutant neurons reveal enlarged and irregular synaptic
      boutons with dense accumulation of synaptic vesicles. Taken together, these data
      show that dFMRP is a potent negative regulator of neuronal architecture and
      synaptic differentiation in both peripheral and central nervous systems.

PMID- 15498497
TI  - Control of embryonic spindle positioning and Galpha activity by C. elegans RIC-8.
AB  - Asymmetric spindle positioning is of fundamental importance for generating cell
      diversity during development. In the C. elegans 1 cell embryo, spindle
      positioning has been shown to depend on heterotrimeric G protein signaling. Two
      Galpha subunits, GOA-1 and GPA-16 (hereafter Galpha), and receptor independent
      activators of G protein signaling GPR-1 and GPR-2 (GPR-1/2) are required for
      proper regulation of spindle positioning . However, it remains unclear whether
      Galpha regulates spindle positioning in its GDP or GTP bound form. Here, we
      investigate the role of RIC-8 in this pathway. RIC-8 was genetically shown to act
      in concert with goa-1 to regulate centrosome movements in C. elegans .
      Interestingly, mammalian RIC-8 was recently found to behave as a GEF for Galpha
      subunits in vitro . We show that reduction of function of ric-8 results in a 1
      cell embryo phenotype very similar to the phenotype of embryos depleted of
      Galpha. RIC-8 is able to directly bind to GOA-1, preferentially to GOA-1-GDP,
      consistent with a GEF role. RIC-8 is localized at the embryo cortex, and its
      activity is essential for the asymmetric localization of GPR-1/2. We suggest that
      RIC-8 directly modulates Galpha activity and that Galpha-GTP is the signaling
      molecule regulating spindle positioning in the early embryo.

PMID- 15498498
TI  - Protein kinase A, which regulates intracellular transport, forms complexes with
      molecular motors on organelles.
AB  - Major signaling cascades have been shown to play a role in the regulation of
      intracellular organelle transport . Aggregation and dispersion of pigment
      granules in melanophores are regulated by the second messenger cAMP through the
      protein kinase A (PKA) signaling pathway ; however, the exact mechanisms of this
      regulation are poorly understood. To study the role of signaling molecules in the
      regulation of pigment transport in melanophores, we have asked the question
      whether the components of the cAMP-signaling pathway are bound to pigment
      granules and whether they interact with molecular motors to regulate the granule
      movement throughout the cytoplasm. We found that purified pigment granules
      contain PKA and scaffolding proteins and that PKA associates with pigment
      granules in cells. Furthermore, we found that the PKA regulatory subunit forms
      two separate complexes, one with cytoplasmic dynein ("aggregation complex") and
      one with kinesin II and myosin V ("dispersion complex"), and that the removal of
      PKA from granules causes dissociation of dynein and disruption of dynein
      dependent pigment aggregation. We conclude that cytoplasmic organelles contain
      protein complexes that include motor proteins and signaling molecules involved in
      different components of intracellular transport. We propose to call such
      complexes 'regulated motor units' (RMU).

PMID- 15498500
TI  - Prodrug research: futile or fertile?
AB  - The objective of this Commentary is to help clarify and illustrate what prodrugs
      are, what they are not, which benefits they can offer, and what their limits are.
      To this end, a number of criteria of classification and evaluation are presented.
      This is followed by a discussion of the pharmaceutical, pharmacokinetic and
      pharmacodynamic objectives of prodrug research. Recent examples (e.g.
      oseltamivir, bambuterol, capecitabine, clopidogrel and tirapazamine) are
      discussed in a biochemical perspective to illustrate these objectives and to
      demonstrate some of the therapeutic benefits afforded by successful prodrugs.
      Attention is also called to the fact that the in vitro and in vivo behavior of
      prodrug candidates may differ from that of the parent drug in ways that go beyond
      the original pharmaceutical, pharmacokinetic or pharmacodynamic objective being
      pursued. We conclude that prodrugs offer a viable strategy to disentangle
      pharmacodynamic and pharmacokinetic optimization.

PMID- 15498499
TI  - The inositol 1,4,5-trisphosphate receptor regulates epidermal cell migration in
      Caenorhabditis elegans.
AB  - Polarized migration and spreading of epithelial sheets is important during many
      processes in vivo, including embryogenesis and wound healing. However, the
      signaling pathways that regulate epithelial migrations are poorly understood. To
      identify molecular components that regulate the spreading of epithelial sheets,
      we performed a screen for mutations that perturb epidermal cell migration during
      embryogenesis in Caenorhabditis elegans. We identified one mutant (jc5) as a weak
      mutation in itr-1, which encodes the single inositol 1,4,5-trisphosphate receptor
      (ITR) in C. elegans. During the migration of the embryonic epidermis, jc5 embryos
      display defects including misdirected migration or premature cessation of
      migration. Cells that halt their migration have disorganized F-actin and display
      reduced filopodial protrusive activity at their leading edge. Furthermore, some
      filopodia formed by epidermal cells in itr-1(jc5) embryos exhibit abnormally long
      lifetimes. Pharmacological studies with the inositol 1,4,5-trisphosphate
      antagonist xestospongin C phenocopy these defects, confirming that ITR function
      is important for proper epidermal migration. Our results provide the first
      molecular evidence that movements of embryonic epithelial cell sheets can be
      controlled by ITRs and suggest that such regulation may be a widespread mechanism
      for coordinating epithelial cell movements during embryogenesis.

PMID- 15498501
TI  - Pharmacological and biological evaluation of a series of substituted 1,4
      naphthoquinone bioreductive drugs.
AB  - The indolequinone compound EO9 has good pharmacodynamic properties in terms of
      bioreductive activation and selectivity for either NAD(P)H:quinone oxidoreductase
      1 (NQO1)-rich aerobic or NQO1-deficient hypoxic cells. However, its
      pharmacokinetic properties are poor and this fact is believed to be a major
      reason for EO9's lack of clinical efficacy. The purpose of this study was to
      develop quinone-based bioreductive drugs that retained EO9's good properties, in
      terms of bioreductive activation, but have improved pharmacokinetic properties.
      Out of 11 naphthoquinone compounds evaluated, 2-aziridinyl-5-hydroxy-1,4
      naphthoquinone (compound 2), 2,3-bis(aziridinyl)-5-hydroxy-1,4-naphthoquinone
      (compound 3), and 2-aziridinyl-6-hydroxymethyl-1,4-naphthoquinone (compound 11)
      were selected for further evaluation based on good substrate specificity for NQO1
      and selectivity towards NQO1-rich cells in vitro. Compound 3 was of particular
      interest as it also demonstrated selectivity for NQO1-rich cells under hypoxic
      conditions. Compound 3 was not metabolised by murine whole blood in vitro (in
      contrast to compounds 2, 11 and EO9) and pharmacokinetic studies in non-tumour
      bearing mice in vivo (at the maximum soluble dose of 60 mg kg(-1) administered
      intraperitoneally) demonstrated significant improvements in plasma half-life
      (16.2 min) and AUC values (22.5 microM h) compared to EO9 (T(1/2) = 1.8 min, AUC
      = 0.184 microM h). Compound 3 also demonstrated significant anti-tumour activity
      against H460 and HCT-116 human tumour xenografts in vivo, whereas EO9 was
      inactive against these tumours. In conclusion, compound 3 is a promising lead
      compound that may target both aerobic and hypoxic fractions of NQO1-rich tumours
      and further studies to elucidate its mechanism of action and improve solubility
      are warranted.

PMID- 15498502
TI  - Differences in binding properties of two proton pump inhibitors on the gastric
      H+,K+-ATPase in vivo.
AB  - Restoration of acid secretion after treatment with covalently-bound proton pump
      inhibitors may depend on protein turnover and on reversal of inhibition by
      reducing agents such as glutathione. Glutathione incubation of the H(+),K(+)
      ATPase isolated from omeprazole or pantoprazole-treated rats reversed 88% of the
      omeprazole inhibition but none of the pantoprazole inhibition. The present study
      was designed to measure binding properties of omeprazole or pantoprazole in vivo.
      Rats were injected with (14)C-omeprazole or (14)C-pantoprazole after acid
      stimulation. The specific binding to the gastric H(+),K(+)-ATPase was measured at
      timed intervals as well as reversal of binding by glutathione reduction. The
      stoichiometry of omeprazole and pantoprazole binding to the catalytic subunit of
      the H(+),K(+)-ATPase was 2 moles of inhibitor per mole of the H(+),K(+)-ATPase
      phosphoenzyme. Omeprazole bound to one cysteine between transmembrane segments
      5/6 and one between 7/8, pantoprazole only to the two cysteines in the TM5/6
      domain. Loss of drug from the pump was biphasic, the fast component accounted for
      84% of omeprazole binding and 51% of pantoprazole binding. Similarly, only 16% of
      omeprazole binding but 40% of pantoprazole binding was not reversed by
      glutathione. The residence time of omeprazole and pantoprazole on the ATPase in
      vivo depends on the reversibility of binding. Binding of pantoprazole at cysteine
      822 is irreversible whereas that of omeprazole at cysteine 813 and 892 is
      reversible both in vivo and in vitro. This is consistent with the luminal
      exposure of cysteine 813 and 892 and the intra-membranal location of cysteine 822
      in the 3D structure of the H(+),K(+)-ATPase.

PMID- 15498503
TI  - Stimulation of proliferation and migration of a colorectal cancer cell line by
      amidated and glycine-extended gastrin-releasing peptide via the same receptor.
AB  - Although amidated forms of gastrin-releasing peptide (GRP) have been identified
      as autocrine growth factors in small cell lung cancer, their role in the
      development and progression of colorectal carcinoma is less clear. In addition,
      the biological activity of non-amidated gastrin-releasing peptide has not been
      investigated in colorectal carcinoma cells. We therefore investigated the effect
      of bombesin (a homologue of gastrin-releasing peptide) on proliferation,
      migration and inositol phosphate production in the human colorectal carcinoma
      cell line DLD-1, and determined the ability of gastrin-releasing peptide receptor
      antagonists to inhibit these effects. We also compared the biological activities
      of amidated and non-amidated GRP in the same assays. Treatment with either
      bombesin, or amidated or non-amidated GRP resulted in significant increase in
      proliferation, and in migration in a wound-healing assay. Both the mitogenic and
      migratory effects of amidated and non-amidated forms were inhibited by the GRP
      receptor antagonist [D-Phe(6), Leu-NHet(13), des-Met(14)]-bombesin(6-13). The
      presence of GRP receptor mRNA and GRP binding sites in three colorectal carcinoma
      cell lines was demonstrated by RT-PCR and by binding of radiolabelled bombesin,
      respectively. Transfection of DLD-1 cells with a dominant negative
      phosphatidylinositol 3-kinase did not affect bombesin-stimulated cell
      proliferation, but inhibited bombesin-stimulated cell migration. Bombesin and
      GRPgly activated phospholipase C, mitogen-activated protein kinase and focal
      adhesion kinase. We conclude that both amidated and non-amidated forms of gastrin
      releasing peptide accelerate proliferation and migration of DLD-1 human
      colorectal carcinoma cells via the gastrin-releasing peptide receptor, but that
      phosphatidylinositol 3-kinase is only involved in the cell migration signalling
      pathway. Our results suggest a potential role for gastrin-releasing peptide
      receptor antagonists in the management of colorectal carcinoma.

PMID- 15498504
TI  - Peroxisome proliferator-activated receptor alpha regulates B lymphocyte
      development via an indirect pathway in mice.
AB  - Peroxisome proliferator-activator receptor alpha (PPARalpha), a member of the
      nuclear receptor superfamily, has been implicated in the regulation of
      inflammation and immune response. Adaptive immune responses are suppressed by
      exposure to PPARalpha agonists, resulting in severe thymus and spleen atrophy. In
      addition, the decline in both T and B cells is due in part to the loss of
      splenocytes upon exposure to PPARalpha agonists. Thus, the current study was
      designed to examine the effect of Wy-14,643, a potent PPARalpha agonist, on B
      cell development in bone marrow from wild-type and PPARalpha-null mice.
      Significantly decrease in pro/pre-B cell and total B220(+) cell was observed in
      wild-type mice in bone marrow upon Wy-14,643 treatment, but not in PPARalpha-null
      mice. Immature and mature B cell populations are not affected. This suggests that
      PPARalpha is involved in the development of B cell during lymphoid lineage.
      However, surprisingly, PPARalpha mRNA was absent in bone marrow as revealed by RT
      PCR. Therefore, the effect of PPARalpha on B cell development is by an indirect
      mechanism.

PMID- 15498505
TI  - Kininogenase activity of Thalassophryne nattereri fish venom.
AB  - Accidents caused by the venomous fish Thalassophryne nattereri are characterized
      by edema, intense pain and necrosis at the site of the sting. This study assessed
      the nociceptive and edematogenic activities of T. nattereri venom after injection
      into the mouse hindpaw and determination of the paw licking duration and weight.
      Subplantar injections of the venom (0.1-6 microg) induced a dose-related increase
      of the paw licking time and paw swelling with maximal values at 3 microg (209.5
      +/- 57.5 s and 135.0 +/- 6.8 mg, respectively). Pretreatment of mice with either
      indomethacin (10 mg/kg, i.p.), a cyclooxygenase inhibitor, dexamethasone (1
      mg/kg, s.c.), a steroid anti-inflammatory agent, cyproheptadine (1 mg/kg, i.p.),
      antagonist of serotonin receptors or L-NAME (100 mg/kg, s.c.), inhibitor of
      nitric oxide syntase, did not affect the venom-induced nociceptive and
      edematogenic responses. Injection of the opioid analgesic fentanyl (0.1 mg/kg,
      s.c.) reduced the paw licking time induced by 1 microg venom by 84% of control,
      without affecting the paw swelling. Both nociceptive and edematogenic responses
      were reduced after treatment with a specific tissue kallikrein inhibitor (TKI,
      100 mg/kg, i.p.) by 78% and 24% from control values, respectively. Administration
      of a specific plasma kallikrein inhibitor (PKSI(527,) 100 mg/kg, s.c.) did not
      affect the venom-induced nociceptive response, but it decreased the paw edema by
      15% from control. After injection of the angiotensin-converting enzyme inhibitor
      captopril (100 mg/kg, i.p.) the venom-induced nociceptive end edematogenic
      responses were increased by two-fold. The role of kallikreins possibly present in
      the venom was further assessed by hydrolysis of human kininogen and kininogen
      derived synthetic peptides, showing the release of kallidin (Lys-bradykinin). The
      hydrolysis was inhibited by metal chelating agents but not by serino-, aspartyl-
      or cysteino-proteinase inhibitors. The data suggest that a protease with tissue
      kallikrein-like activity plays a major role in nociception and edema induced by
      T. nattereri venom and this should be considered to achieve efficient treatments
      for human accidents with this venom.

PMID- 15498506
TI  - Relation between the ability of some compounds to modulate the MRP1-mediated
      efflux of glutathione and to inhibit the MRPl-mediated efflux of daunorubicin.
AB  - Much effort has been recently directed to identify the transport-modulating
      agents in order to overcome the P-gp- and MRP1-mediated drug resistance. Contrary
      to what is observed for P-gp, very few compounds have been shown to reverse multi
      drug resistance (MDR) mediated by MRP1. On the other hand, despite of critical
      role of GSH in transporting the MRP1 substrates, not much is known about GSH
      interactions with MRP1. In this work, three compounds that were shown to inhibit
      the MRP1-mediated efflux of daunorubicin (DNR) have been studied. Depending on
      their nature the selected compounds have different effects, e.g. at 40 microM,
      verapamil inhibits 50% of DNR efflux whereas GSH efflux is increased about two
      fold. PAK-104P has shown the same effect, i.e. the inhibition of the MRP1
      mediated efflux of DNR is accompanied by a stimulation of GSH efflux. However,
      the PAK-104P concentration required to obtain the same effect is about 40 times
      smaller that in the case of verapamil. MK571 has been shown to inhibit the efflux
      of both DNR and GSH. Based on these observations and those reported earlier, a
      working model is proposed.

PMID- 15498507
TI  - Catalase induces the expression of inducible nitric oxide synthase through
      activation of NF-kappaB and PI3K signaling pathway in Raw 264.7 cells.
AB  - It has been reported that macrophages produce substantial amounts of nitrite and
      nitrate after addition of catalase, but the mechanism associated remains unclear.
      In present study, we investigated whether catalase modulates the expression of
      inducible nitric oxide synthase (iNOS), an enzyme that produces nitric oxide.
      Exposure of Raw 264.7 macrophages (Raw cells) to catalase induced high expression
      of iNOS mRNA as well as protein with enzymatic activity. Data of mechanical
      analyses, such as iNOS promoter-driven luciferase assay and actinomycin D chase
      experiments demonstrated that the induction was due to increased iNOS
      transcription and post-transcriptional iNOS mRNA stability. Of interest, catalase
      induced iNOS protein expression was abrogated through inactivation of NF-kappaB
      pathway by MG132 or BAY 11-7085 and PI3K pathway by LY294002 or wortmannin,
      respectively. In particular, blockage of PI3K pathway by LY294002 down-regulated
      iNOS transcription and steady-state iNOS mRNA levels as well as iNOS mRNA
      stability induced by catalase, suggesting regulation of PI3K pathway in catalase
      induced iNOS expression at the levels of iNOS transcription, steady-state mRNA
      status, and mRNA stability. Additional cell culture works in different types of
      cells indicated that iNOS expression by catalase might be cell type-specific,
      based on the facts that catalase induced iNOS expression in BV2 microglial
      macrophage-like cells, but not in HT-29 or A549, human colon or lung cancer
      epithelial-like cells. Together, these results demonstrate for the first time
      that catalase induces iNOS expression in Raw cells, which seems to be associated
      with the increase of iNOS transcription and mRNA stability as well as the
      activation of NF-kappaB and PI3K signaling pathways.

PMID- 15498508
TI  - Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid-
      and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis.
AB  - All-trans retinoic acid (ATRA) and Am80 are natural and synthetic derivatives of
      Vitamin A and have been used in the fields of oncology and dermatology for years.
      Their action was considered to be achieved mainly through binding to nuclear
      hormone receptors, retinoic acid receptors (RARs), although they have been
      observed to have different biological effects. For example, the two compounds
      have similar effects on differentiation but different effects on proliferation in
      human promyelocytic leukemia cell line HL-60 cells. To elucidate the genes
      responsible for this and other differences, we attempted for the first time to
      determine the genes whose expressions were differentially modulated during the
      time course of HL-60 cell differentiation by ATRA and Am80 treatment up to 72h
      utilizing DNA microarray and clustering analyses. As a result, the expressions of
      204 genes were found to be modulated differentially by ATRA and Am80. Among them,
      we focused on two components of the PI3-kinase/Akt signal transduction pathway,
      phosphoinositide-3-kinase, beta-catalytic subunit and ribosomal protein S6 kinase
      polypeptide 1, which are related to the regulation of cell proliferation and
      apoptosis. Their expressions were specifically suppressed by ATRA, which
      coincided with the suppressive effects of ATRA on the HL-60 cell proliferation.
      Moreover, PI3-kinase inhibitors suppressed the proliferation of Am80-treated
      cells to the same extent as ATRA did. These results indicated that these gene
      products play a role in HL-60 cell growth suppression during the late stage of
      differentiation. The complete data and a list of the genes are available at .

PMID- 15498509
TI  - Effects of synthetic sphingosine-1-phosphate analogs on arachidonic acid
      metabolism and cell death.
AB  - Sphingolipid metabolites such as sphingosine regulate cell functions including
      cell death and arachidonic acid (AA) metabolism. D-erythro-C18-Sphingosine-1
      phosphate (D-e-S1P), a sphingolipid metabolite, acts as an intracellular
      messenger in addition to being an endogenous ligand of some cell surface
      receptors. The development of S1P analogs may be useful for studying and/or
      regulating S1P-mediated cellular responses. In the present study, we found that
      several synthetic S1P analogs at pharmacological concentrations stimulated AA
      metabolism and cell death in PC12 cells. D-erythro-N,O,O-Trimethyl-C18-S1P (D-e
      TM-S1P), L-threo-O,O-dimethyl-C18-S1P (L-t-DM-S1P) and L-threo-O,O-dimethyl-3O
      benzyl-C18-S1P (L-t-DMBn-S1P) at 100 microM stimulated [(3)H]AA release from the
      prelabeled PC12 cells. L-t-DMBn-S1P at 20 microM increased prostanoid formation
      in PC12 cells. L-t-DMBn-S1P-induced AA release was inhibited by D-e-sphingosine,
      but not by the tested PLA(2) inhibitors. L-t-DMBn-S1P did not stimulate the
      activity of cytosolic phospholipase A(2alpha) (cPLA(2alpha)) in vitro and the
      translocation of cPLA(2alpha) in the cells, and caused AA release from the cells
      lacking cPLA(2alpha). These findings suggest that L-t-DMBn-S1P stimulated AA
      release in a cPLA(2alpha)-independent manner. In contrast, D-e-S1P and D-erythro
      N-monomethyl-C18-S1P caused cell death without AA release in PC12 cells, and the
      effects of D-e-TM-S1P, L-t-DM-S1P and L-t-DMBn-S1P on cell death were limited.
      Synthetic S1P analogs may be useful tools for studying AA metabolism and cell
      death in cells.

PMID- 15498510
TI  - Ibuprofen-induced Walker 256 tumor cell death: cytochrome c release from
      functional mitochondria and enhancement by calcineurin inhibition.
AB  - The participation of mitochondria in the mechanism of tumor cell death induced by
      non-steroid anti-inflammatory drugs is uncertain. Here we show that ibuprofen
      induces death of Walker 256 tumor cells independently on mitochondrial
      depolarization as estimated by flow cytometry using DioC(6)(3). Oligomycin
      increased mitochondrial transmembrane potential in both ibuprofen-treated and non
      treated cells, indicating that ATP synthesis was sustained during cell death.
      Cyclosporin A, but not bongkrekic acid, both mitochondrial permeability
      transition inhibitors, increased the percentage of cell death in the presence of
      ibuprofen. FK506, a calcineurin inhibitor like cyclosporin A, also increased
      ibuprofen-induced cell death. Moreover, we showed that cytochrome c was released
      during ibuprofen-induced cell death. In conclusion, death of Walker 256 tumor
      cells induced by ibuprofen does not impair mitochondrial function, involves
      cytochrome c release and is accompanied by a rescue pathway via calcineurin
      activation.

PMID- 15498511
TI  - Effects of anandamide on the binding and signaling properties of M1 muscarinic
      acetylcholine receptors.
AB  - This study investigated the effects of the endocannabinoid, anandamide, on M(1)
      muscarinic acetylcholine receptors (mAChRs) expressed in Chinese hamster ovary
      (CHO) cells. In the presence of anandamide, [(3)H]N-methylscopolamine ([(3)H]NMS)
      inhibition binding was characterized by Hill coefficients greater than 1 while
      saturation binding isotherms were characterized by a reduction in radioligand
      B(max). Anandamide did not affect the potency of classic agonists, antagonists or
      allosteric modulators to inhibit [(3)H]NMS binding, indicating that the site of
      anandamide action did not involve receptor regions recognized by these compounds.
      Although the mode of binding of anandamide was reversible, the order of ligand
      addition was important; the inhibitory effect was greatest when anandamide was
      equilibrated with the receptor prior to radioligand addition, and weakest in the
      converse situation. Interestingly, the inhibitory potency of anandamide was
      reduced on pre-equilibration with non-transfected CHO cell membranes, prior to
      addition of M(1) mAChR-transfected membranes. In phosphoinositide (PI) hydrolysis
      assays, anandamide significantly reduced the maximal response to acetylcholine,
      but at higher concentrations than those needed to fully inhibit radioligand
      binding. Studies utilizing a range of agonists with varying intrinsic activities
      showed that the inhibitory effects of anandamide on agonist function were most
      pronounced with the lowest efficacy agonists. These findings suggest that the
      mechanism of action of anandamide at the M(1) mAChR involves perturbation of the
      receptor via the membrane in a manner that is sensitive to the conformation of
      the receptor (occupied versus vacant).

PMID- 15498512
TI  - Induction of Cdc25B expression by epidermal growth factor and transforming growth
      factor-alpha.
AB  - The dual specificity protein phosphatase Cdc25B regulates of the mitotic cell
      cycle checkpoint and is over expressed in human tumors. Given the importance of
      growth factors in initiating and sustaining cell proliferation, we examined their
      effects on Cdc25B protein expression in human cancer cells. Within 1h after
      epidermal growth factor (EGF) or transforming growth factor-alpha (TGF-alpha)
      treatment, Cdc25B protein levels increased in growth factor responsive A549 and
      SCC25 cells, but not in non-responsive MDA-MB-231 cells. A functional consequence
      of elevated Cdc25B was implied by the concomitant decrease in phosphorylated
      cyclin dependent kinase, a known Cdc25B substrate, after growth factor treatment
      of A549 and SCC25 cells. The EGF-mediated induction of Cdc25B required a
      functional EGF receptor (ErbB1), as mouse embryonic fibroblasts lacking ErbB1 did
      not have increased Cdc25B levels after EGF treatment. Moreover, the EGFR receptor
      selective tyrosine kinase inhibitor AG1478 and mitogen activated kinase kinase
      inhibitor U0126 blocked growth factor-mediated Cdc25B induction. Thus, EGF and
      TGF-alpha appear to induce cellular Cdc25B through the mitogen-activated protein
      kinase pathway.

PMID- 15498513
TI  - Differential type 4 cAMP-specific phosphodiesterase (PDE4) expression and
      functional sensitivity to PDE4 inhibitors among rats, monkeys and humans.
AB  - It has been suggested that the rat is relatively more susceptible to toxicity
      induced by inhibitors for type 4 cAMP-specific phosphodiesterase (PDE4). In this
      study designed to elucidate possible biochemical basis for the higher
      susceptibility, we compared PDE4 expression levels and their functional relevance
      among rats, monkeys and humans. In several toxicologically relevant tissues and
      blood leukocytes, the mRNA expression levels of PDEs 4A, 4B, 4C and 4D were
      significantly higher in rats than in humans. We confirmed that higher PDE4
      expression levels were correlated with a higher enzyme activity level in rat
      leukocytes. The PDE4 enzyme activity level of leukocytes in monkeys fell between
      that of rats and humans. Functionally, the potencies of the PDE4 inhibitors
      rolipram, SB 207499 and SCH 351591 in inhibiting tumor necrosis factor production
      from leukocytes were in the following order: rat > monkey > human. In addition,
      rolipram was about 10-fold more potent in rats than in humans in inhibiting
      phenylephrine-induced contraction of renal artery. These inhibitors were
      confirmed to be highly selective for PDE4 in comparison to all other PDE
      families, and to inhibit rat and human PDE4s with identical potencies. Taken
      together, these results suggest that the higher susceptibility of rats to PDE4
      inhibitor-induced toxicity might be due to their higher expression levels of
      PDE4, and that PDE4 inhibitors may be safer in humans than in monkeys and,
      particularly, rats.

PMID- 15498514
TI  - Kinetic analysis of interactions between human acetylcholinesterase, structurally
      different organophosphorus compounds and oximes.
AB  - The wide-spread use of organophosphorus compounds (OP) as pesticides and the
      availability of highly toxic OP-type chemical warfare agents (nerve agents)
      underlines the necessity for an effective medical treatment. Acute OP toxicity is
      primarily caused by inhibition of acetylcholinesterase (AChE, EC 3.1.1.7).
      Reactivators (oximes) of inhibited AChE are a mainstay of treatment, however, the
      commercially available compounds, obidoxime and pralidoxime, are considered to be
      rather ineffective against various nerve agents. The antidotal efficacy of new
      oximes is primarily tested in animals for ethical reasons. However, the various
      interactions between AChE, OP and oximes can be investigated with human AChE
      which enables the direct assessment of oxime potency, thus excluding species
      differences. The kinetics of inhibition, reactivation and aging were investigated
      with human erythrocyte AChE, various structurally different OP (organophosphates,
      -phosphonates and phosphoramidates) and oximes (obidoxime, pralidoxime, HI 6, HLo
      7). The inhibitory potency of OPs, reactivating potency of oximes and spontaneous
      reactivation and aging were strongly affected by the structural characteristics
      of the OPs and of the phosphyl-AChE-complex. The kinetic data emphasize the
      superior inhibitory potency of organophosphonates. AChE inhibited by various
      phosphoramidates was mostly resistant towards reactivation by oximes while
      phosphonylated AChE was easily reactivated. HLo 7 was most potent with
      phosphonylated AChE and obidoxime with AChE inhibited by organophosphates and
      phosphoramidates. With the exception of soman, OP-inhibited AChE aged rather
      slowly (t(1/2) 3-231 h) and reactivated spontaneously with some compounds. These
      results indicate that there is obviously no direct structure-activity
      relationship for the various interactions of human AChE, OPs and oximes.

PMID- 15498515
TI  - A gene expression signature for oxidant stress/reactive metabolites in rat liver.
AB  - Formation of free radicals and other reactive molecules is responsible for the
      adverse effects produced by a number of hepatotoxic compounds. cDNA microarray
      technology was used to compare transcriptional profiles elicited by training and
      testing sets of 15 oxidant stressors/reactive metabolite treatments to those
      produced by approximately 85 other paradigm compounds (mostly hepatotoxicants) to
      determine a shared signature profile for oxidant stress-associated
      hepatotoxicity. Initially, 100 genes were chosen that responded significantly
      different to oxidant stressors/reactive metabolites (OS/RM) compared to other
      samples in the database, then a 25-gene subset was selected by multivariate
      analysis. Many of the selected genes (e.g., aflatoxin aldehyde reductase,
      diaphorase, epoxide hydrolase, heme oxgenase and several glutathione
      transferases) are well-characterized oxidant stress/Nrf-2-responsive genes. Less
      than 10 other compounds co-cluster with our training and testing set compounds
      and these are known to generate OS/RMs as part of their mechanisms of toxicity.
      Using OS/RM signature gene sets, compounds previously associated with macrophage
      activation formed a distinct cluster separate from OS/RM and other compounds. A
      69-gene set was chosen to maximally separate compounds in control, macrophage
      activator, peroxisome proliferator and OS/RM classes. The ease with which these
      'oxidative stressor' classes can be separated indicates a role for microarray
      technology in early prediction and classification of hepatotoxicants. The ability
      to rapidly screen the oxidant stress potential of compounds may aid in avoidance
      of some idiosyncratic drug reactions as well as overtly toxic compounds.

PMID- 15498516
TI  - Influence of phenylalanine 120 on cytochrome P450 2D6 catalytic selectivity and
      regiospecificity: crucial role in 7-methoxy-4-(aminomethyl)-coumarin metabolism.
AB  - The polymorphic human debrisoquine hydroxylase, cytochrome P450 2D6 (CYP2D6), is
      one of the most important phase I drug metabolising enzymes. It is responsible
      for metabolising a large number of compounds that mostly share similarity in
      having a basic N-atom and an aromatic moiety. In homology modelling studies, it
      has been suggested that in fixation of this aromatic moiety, there may be an
      important role for phenylalanine 120 (Phe(120)). In this study, the role of
      Phe(120) in ligand binding and catalysis was experimentally examined by mutating
      it into an alanine. Strikingly, this substitution led to a completely abolished 7
      methoxy-4-(aminomethyl)-coumarin (MAMC) O-demethylating activity of CYP2D6. On
      the other hand, bufuralol metabolism was hardly affected (K(m) of 1-hydroxylation
      mutant: 1.2 microM, wild-type: 2.9 microM, 4-hydroxylation mutant: 1.5 microM,
      and wild-type: 3.2 microM) and neither was affected dextromethorphan O
      demethylation (K(m) mutant: 1.2 microM, wild-type: 2 microM, k(cat) mutant: 4.5
      min(-1), and wild-type: 3.3 min(-1)). However, the Phe(120)Ala mutant also formed
      3-hydroxymorphinan, the double demethylated form of dextromethorphan, which was
      not detected using wild-type CYP2D6. 3,4-Methylenedioxymethamphetamine (MDMA) was
      demethylenated by both mutant and wild-type CYP2D6 to 3,4
      dihydroxymethamphetamine (3,4-OH-MA K(m) of mutant: 55 microM and wild-type: 2
      microM). In addition, the mutant formed two additional metabolites; 3,4
      methylenedioxyamphetamine (MDA) and N-hydroxy-3,4-methylenedioxymethamphetamine
      (N-OH-MDMA). Inhibition experiments of dextromethorphan O-demethylation showed a
      decreased affinity of the Phe(120)Ala mutant for quinidine (IC(50) mutant: 240 nM
      and wild-type, 40 nM), while IC(50)s for quinine were equal (1 microM). These
      data indicate the importance of Phe(120) in the selectivity and regiospecificity
      in substrate binding and catalysis by CYP2D6.

PMID- 15498517
TI  - A methylester of the glucuronide prodrug DOX-GA3 for improvement of tumor
      selective chemotherapy.
AB  - The glucuronide prodrug of doxorubicin, DOX-GA3, can be selectively activated in
      tumors by extracellular human beta-glucuronidase, resulting in a better
      therapeutic index than doxorubicin. DOX-GA3, however, is rapidly excreted by the
      kidney. We hypothesized that slow release of DOX-GA3 from its methylester, DOX
      mGA3, by esterase activity in blood would result in improved circulation half
      life (t(1/2)) of DOX-GA3. DOX-mGA3 was synthesized more efficiently with an
      overall yield of 60% as compared to 37% in the case of DOX-GA3. We showed that
      DOX-mGA3 was enzymatically converted to DOX-GA3 with a t(1/2) of approximately
      0.5 min in mouse plasma to 2.5 h in human plasma, which was in agreement with
      differences in esterase activity between species. DOX-mGA3, similar to DOX-GA3,
      was at least 37-fold less potent than the parent drug doxorubicin in growth
      inhibition of four different human malignant cell lines in vitro. Incubation of
      OVCAR-3 cells with DOX-mGA3 in combination with an excess of human beta
      glucuronidase (0.05 U mL(-1)) resulted in a similar growth inhibition to that of
      doxorubicin. Intravenous administration of DOX-mGA3 in FMa-bearing mice resulted
      in an area under the concentration versus time curve (AUC) of DOX-GA3 in tumor
      and most normal tissues that was 2.5- to 3-fold higher than after the same dose
      of DOX-GA3 itself. In tumor tissue, this was accompanied by a 2.7-fold increase
      in the AUC of doxorubicin from DOX-mGA3 than from DOX-GA3. In conclusion, an
      advantage of DOX-mGA3 over DOX-GA3 is that this prodrug can be produced with a
      higher yield. Another important advantage is the improved pharmacokinetics of the
      lipophilic DOX-mGA3 as compared to that of the hydrophilic DOX-GA3. This effect
      may even be more pronounced in man, because of the lower plasma esterase activity
      than measured in mice.

PMID- 15498518
TI  - A novel therapy for acute hepatitis utilizing dehydroepiandrosterone in the
      murine model of hepatitis.
AB  - Dehydroepiandrosterone (DHEA), one of the major androgens secreted by the adrenal
      cortex, has been shown to have potential immunoreguratory properties. In this
      study, we examined the effect of DHEA in a mouse model of hepatitis. Mice were
      treated with DHEA and injected with concanavalin A (Con A) or lipopolysaccharide
      (LPS)/D-galactosamine (GalN). Cytokine expression was measured by quantitative RT
      PCR and ELISA. Apoptosis was detected by the TUNEL method and by DNA
      fragmentation analysis. In the DHEA-treated mice, the serum levels of ALT and
      expression of inflammatory mediators were significantly decreased. The number of
      apoptotic cells was also much lower than that observed in control, untreated
      mouse liver tissue. There were fewer tumor necrosis factor-alpha (TNF-alpha)
      induced apoptotic cells in H4IIE hepatoma cells treated with DHEA than in non
      treated cells. DHEA decreased the expression levels of mRNA transcripts encoding
      TNF-alpha and iNOS. These results suggest that DHEA can reduce T-cell-mediated
      injury in the liver as manifest by inhibition of the expression of several
      inflammatory mediators and hepatocyte apoptosis. DHEA should, thus, be considered
      as a novel candidate for the therapy of liver injury.

PMID- 15498519
TI  - Intrahepatic flow disturbance by clomipramine in the isolated perfused rat liver.
AB  - Intrahepatic flow disturbance may have important pharmacological and
      toxicological significance. However, apart from pathological conditions, flow
      disturbance by drugs has received little attention. In the isolated perfused rat
      liver (IPRL), we found that infusion of tricyclic antidepressants increased
      portal perfusion pressure (PP) with a coincidental decrease in oxygen uptake at
      concentrations of 3-30 microM; the order of potency was clomipramine >
      amitriptyline > imipramine approximately nortriptyline >> desipramine. The
      characteristics of clomipramine action were as follows: (1) The extrahepatic
      portal vein was much less sensitive to clomipramine than the IPRL. (2) Changes in
      PP and oxygen uptake required Ca(2+) in the perfusate and were inhibited by
      papaverine, staurosporine, sodium nitroprusside and indomethacin. (3) Compared
      with endothelin-1, clomipramine produced a greater decrease in the ratio of
      oxygen uptake/PP together with a greater overflow of loaded indocyanine green for
      an increase in PP by about 2 cm H(2)O. (4) Vital staining with trypan blue and
      rhodamine 6G and histological examinations revealed that 3-10 microM clomipramine
      produced marked flow redistribution due to the constriction of portal vein
      branches. Portal flow was short-circuited to the hepatic vein at a deeper and
      hilar portion of the liver, with minimal perfusion of the periphery. These
      results demonstrate an example of drug-induced intrahepatic flow disturbance in
      vitro. Its contribution to the development of toxicity in vivo remains to be
      studied.

PMID- 15498520
TI  - The use of proteomics for the assessment of clinical samples in research.
AB  - Proteomics, the analysis of expressed proteins, has been an important developing
      area of research for the past two decades [Anderson, NG, Anderson, NL. Twenty
      years of two-dimensional electrophoresis: past, present and future.
      Electrophoresis 1996;17:443-453]. Advances in technology have led to a rapid
      increase in applications to a wide range of samples; from initial experiments
      using cell lines, more complex tissues and biological fluids are now being
      assessed to establish changes in protein expression. A primary aim of clinical
      proteomics is the identification of biomarkers for diagnosis and therapeutic
      intervention of disease, by comparing the proteomic profiles of control and
      disease, and differing physiological states. This expansion into clinical samples
      has not been without difficulties owing to the complexity and dynamic range in
      plasma and human tissues including tissue biopsies. The most widely used
      techniques for analysis of clinical samples are surface-enhanced laser
      desorption/ionisation mass spectrometry (SELDI-MS) and 2-dimensional gel
      electrophoresis (2-DE) coupled to matrix-assisted laser desorption ionisation
      [Person, MD, Monks, TJ, Lau, SS. An integrated approach to identifying chemically
      induced posttranslational modifications using comparative MALDI-MS and targeted
      HPLC-ESI-MS/MS. Chem. Res. Toxicol. 2003;16:598-608]-mass spectroscopy (MALDI
      MS). This review aims to summarise the findings of studies that have used
      proteomic research methods to analyse samples from clinical studies and to assess
      the impact that proteomic techniques have had in assessing clinical samples.

PMID- 15498521
TI  - Venn analysis as part of a bioinformatic approach to prioritize expressed
      sequence tags from cardiac libraries.
AB  - OBJECTIVES: We needed to sort expressed sequence tags (ESTs) from human cardiac
      expression libraries. DESIGN AND METHODS: We annotated DNA sequence text files of
      35,152 cardiac ESTs using our search and annotation tool called Multiblast.pl. We
      generated lists of the most prevalent ESTs in each library, and using a novel
      Venn tool, we grouped ESTs that were common to all or exclusive to particular
      libraries. RESULTS: Hypothetical protein KIAA0553 was expressed 120 times among
      917 ESTs from an adult cardiac library (13.1%) compared only once among 8075 ESTs
      from fetal cardiac libraries (P < 10(-114)), this was confirmed using Northern
      analysis. We collated biochemical features of KIAA0553 and determined DNA
      polymorphism frequencies. We also used the Venn tool to specify genes that were
      uniquely expressed in hypertrophic cardiomyocytes. CONCLUSIONS: Annotating ESTs
      and sorting them using Venn analysis can help specify new candidate disease genes
      from the current lists of "hypothetical proteins".

PMID- 15498522
TI  - Cloning of a kallikrein pseudogene.
AB  - OBJECTIVES: Kallikreins are a group of serine proteases clustered together on a
      small region of chromosome 19q13.4. Recent reports suggest that kallikreins are
      differentially expressed in malignancy and have potential as cancer biomarkers.
      The human kallikrein gene locus has now been fully characterized and 15
      functional kallikreins were identified. Although many kallikrein pseudogenes have
      already been characterized in rodents, none have been identified in humans.
      METHODS AND RESULTS: In the current study, we identified the first human
      kallikrein pseudogene named PsiKLK1 and mapped it between the KLK2 and KLK4
      genes. This pseudogene shares a moderate degree of similarity with the adjacent
      functional kallikreins. It has a conserved histidine residue of the catalytic
      triad of serine proteases and its surrounding motif, but lacks the aspartate and
      serine residues. Positions of some cysteine residues are also conserved in the
      pseudogene. This pseudogene lacks intronic sequences and should thus be
      classified as a processed pseudogene. EST and PCR analyses indicate that this
      pseudogene may be transcriptionally active, because mRNA was detected in many
      tissues including the prostate, testis, pituitary, and adrenal glands, as well as
      in tissues of the female genital organs. DISCUSSION: The mRNA sequence of the
      gene is, however, defective and is not predicted to code for a protein. Highly
      conserved sequences were found in the flanking region of the pseudogene, thus
      supporting the view that it evolved by retrotransposition. We also identified
      another serine protease fragment that has only the conserved histidine residue.
      The functional significance of the pseudogene and the other fragment is yet to be
      identified.

PMID- 15498523
TI  - Maternal plasma concentrations of insulinlike growth factor-1 and insulinlike
      growth factor-binding protein-1 in early pregnancy and subsequent risk of
      preeclampsia.
AB  - OBJECTIVES: We investigated the relationship between maternal plasma free
      insulinlike growth factor-1 (IGF-1) and insulinlike growth factor-binding protein
      1 (IGFBP-1) concentrations and risk of preeclampsia. DESIGN AND METHODS: Maternal
      blood samples were collected at 13 weeks' gestation on average. From the cohort,
      we selected 53 women who developed preeclampsia and 477 who remained
      normotensive. Free IGF-1 and IGFBP-1 concentrations were measured using
      immunoassays. Logistic regression procedures were used to calculate odds ratios
      (OR) and 95% confidence intervals (95% CI). RESULTS: Women who developed
      preeclampsia had 18% and 27% lower concentrations of free IGF-1 and IGFBP-1,
      respectively, than controls (P < 0.05). There was a 57% reduced risk of
      preeclampsia among women with free IGF-1 concentrations of >or= 0.81 ng/mL (OR =
      0.43, 95% CI 0.23-0.83) and a 43% reduced risk among women with IGFBP-1
      concentrations of >or= 72.36 ng/mL (OR = 0.53, 95% CI 0.23-1.21). CONCLUSIONS:
      Alterations of free IGF-1 and IGFBP-1 concentrations in maternal plasma during
      early pregnancy are associated with risk of preeclampsia. These associations may
      help to further elucidate the pathologic processes of preeclampsia.

PMID- 15498524
TI  - Dimethylglycine supplementation does not affect plasma homocysteine
      concentrations in pre-dialysis chronic renal failure patients.
AB  - OBJECTIVE: To determine whether daily dimethylglycine supplementation affects
      plasma homocysteine concentrations. DESIGN AND METHODS: A randomized, blinded,
      crossover design was used. Seven pre-dialysis chronic renal failure patients
      consumed 400 mg of dimethylglycine or placebo daily for 28 days. Fasting blood
      samples and 12-h urine samples were collected at baseline and at the end of each
      treatment period for analysis. RESULTS: No significant differences were observed
      in plasma homocysteine (P = 0.624), glycine betaine (P = 0.452) and methionine (P
      = 0.457) concentrations between dimethylglycine and placebo treatments.
      CONCLUSION: Daily supplementation with dimethylglycine does not affect plasma
      homocysteine.

PMID- 15498525
TI  - Evaluation of an improved blood-conserving POCT sampling system.
AB  - OBJECTIVE: To evaluate a modified point-of-care (POCT) testing i-STAT analyzing
      cartridge that connects directly to the sampling port of a blood-conserving
      sampling line. DESIGN AND METHODS: In an in vitro setup, blood samples were drawn
      from a blood-conserving sampling line connected to a miniature cardiopulmonary
      bypass (CPB) system. Blood collection from the sampling port was either performed
      with a syringe necessitating subsequent sample loading on a standard i-STAT
      cartridge (conventional procedure) or with a modified i-STAT sampling cartridge
      allowing blood flow from the sampling port directly into the cartridge (modified
      procedure). The loaded cartridges were subsequently inserted into the i-STAT
      Portable Clinical Analyzer for sample analysis. Multiple parameters such as blood
      gases, electrolytes, hematocrit, and glucose were measured. A series of 30 paired
      measurements was performed. Corresponding series of values were compared using
      linear regression analysis and Bland-Altman bias analysis (P < 0.05). RESULTS:
      Twenty-five complete measurement series consisting of 12 parameters (pH, pCO(2),
      pO(2), SO(2), base excess, bicarbonate concentration, sodium, potassium, ionized
      calcium, hemoglobin concentration, hematocrit, glucose) were evaluated. Linear
      regression analysis between the two sampling methods tested demonstrated an
      excellent correlation for all parameters (Pearson correlation coefficients: 0.859
      0.999). Bias and precision between corresponding series showed clinically
      acceptable performance levels for all parameters. CONCLUSIONS: The modified i
      STAT sampling cartridge allows reliable diagnostic blood sampling directly from a
      blood-conserving sampling line. The technique presented is also applicable to
      other POCT systems, thus reducing diagnostic blood loss because of the minimal
      amount of blood required for analysis.

PMID- 15498526
TI  - Urinary 5-hydroxy indole acetic acid as a test for early diagnosis of acute
      appendicitis.
AB  - OBJECTIVES: Acute appendicitis (AA) is the most common abdominal emergency. The
      appendix has abundant serotonin containing cells. Upon inflammation, serotonin is
      released in the blood and converted into 5-HIAA (5-hydroxy indole acetic acid).
      Measurement of the urine 5-HIAA (U-5-HIAA) could be a reliable marker of
      inflammation of the appendix. We have compared the powers of test performance of
      spot U-5-HIAA and spot U-5-HIAA/creatinin with other routine laboratory tests
      used for the diagnosis of acute appendicitis. DESIGN AND METHODS: Urine, serum,
      and blood samples of 110 patients who were admitted and observed in the emergency
      units of two university hospitals were studied. 5-HIAA was measured using HPLC, C
      reactive protein by immunoturbidometry, WBC by electronic cell counting, and
      urine creatinine by the Jaffe method. Diagnostic accuracy of the various tests
      was evaluated by receiver operating characteristic (ROC) analysis. FINDINGS: The
      mean of spot U-5-HIAA in 39 patients with AA (nongangrenous) was 32 +/- 2.6
      micromol/L, which was much higher than the mean of 40 non-appendicitis patients
      (NA) (5.5 +/- 0.6), 10 follicular hyperplasia (7.5 +/- 2.1), and 50 healthy
      control cases (4.1 +/- 0.5) with P < 0.001. The concentration of U-5-HIAA in 21
      patients with gangrenous appendicitis (GA) (13.8 +/- 2.1) was also higher than NA
      patients and healthy individuals but lower than AA cases (P < 0.05). Considering
      10 micromol/L as the cutoff point, this test shows 84% sensitivity and 88%
      specificity, with 90% and 81% positive and negative predictive values,
      respectively. The area under ROC curve (AUC) of U-5-HIAA in the diagnosis of AA
      (AUC = 0.903) was much larger than AUCs of U-5-HIAA/Cr (0.787), WBC (0.703), and
      CRP (0.660). CONCLUSION: : Urinary secretion of 5-HIAA increases significantly in
      acute appendicitis and measurement of spot U-5-HIAA gives higher diagnostic
      accuracy than other routine laboratory tests. While the inflammation progresses
      to necrosis of the appendix, the concentration of 5-HIAA decreases. This decrease
      could be a warning sign of perforation of the appendix.

PMID- 15498527
TI  - Oxidizability of apolipoprotein B-containing lipoproteins and serum
      paraoxonase/arylesterase activities in preeclampsia.
AB  - OBJECTIVES: Lipoprotein oxidation has been implicated in the pathogenesis of
      preeclampsia and paraoxonase, an antioxidant enzyme shown to protect lipoproteins
      from being oxidized. The aim of the present study was to evaluate oxidizability
      of apolipoprotein B-containing lipoproteins and serum paraoxonase/arylesterase
      activities in preeclampsia. DESIGN AND METHODS: Twenty-one women with mild
      preeclampsia, 21 women with severe preeclampsia, and 20 women with normal
      uncomplicated pregnancy were included in this study. Serum malondialdehyde (MDA)
      level, an indicator of lipid peroxidation, was measured by high-performance
      liquid chromatography (HPLC). The oxidizability of apolipoprotein B-containing
      lipoproteins was evaluated by copper-induced in vitro peroxidation of the
      isolated fraction of apolipoprotein B-containing lipoproteins coupled with the
      thiobarbituric acid-reactive substances assay and expressed as the difference
      between copper-treated MDA and basal MDA (DeltaMDA). The serum paraoxonase and
      arylesterase activities were determined spectrophotometrically. RESULTS: Serum
      MDA and DeltaMDA levels of apolipoprotein B-containing lipoproteins were
      significantly higher in both mild and severe preeclampsia groups than in the
      normal pregnant group. Serum paraoxonase and arylesterase activities were not
      significantly different among the study groups. CONCLUSIONS: Enhancement in
      oxidizability of apolipoprotein B-containing lipoproteins accompanying with
      dyslipidemia and increased serum MDA levels suggests that those lipoproteins play
      a role in the pathogenesis of preeclampsia. Further studies are needed to
      investigate serum paraoxonase activity in women with normal pregnancies and
      preeclampsia.

PMID- 15498528
TI  - Circulating insulin-like growth factors in patients infected with Helicobacter
      pylori.
AB  - OBJECTIVES: The level of insulin-like growth factors (IGFs) and their binding
      proteins may change in acutely ill humans. The aim of this work was to examine
      the changes in the IGF system in patients suffering from infection induced by
      Helicobacter pylori (H. pylori). DESIGN AND METHODS: The serum concentrations of
      IGF-I, IGF-II and cortisol were measured by radioimmunoassay. IGFBP patterns were
      characterized by ligand-affinity blotting, and a lectin-binding assay was used to
      investigate the possible changes in the glycocomponent of IGFBP-3. RESULTS: Both
      IGF-I and IGF-II concentrations were significantly lower in patients with H.
      pylori infection (P < 0.001 for IGF-I and P = 0.016 for IGF-II) compared to
      healthy individuals, whereas the level of cortisol was significantly elevated in
      analyzed patients (P < 0.001). Autoradiography demonstrated the increased
      presence of IGFBP-2 and IGFBP-1, together with a decreased level of IGFBP-3.
      CONCLUSIONS: The circulating IGF/IGFBP system is altered in patients infected
      with H. pylori. The increased level of cortisol suggests the involvement of the
      hypothalamic/pituitary/adrenal axis that stimulates the elevation of blood
      glucose, probably in coordination with decreased IGF activity to minimize
      anabolic metabolism.

PMID- 15498529
TI  - Homocysteine effect on protein degradation rates.
AB  - OBJECTIVES: To show the effect of homocysteine (Hcy) on the degradation rates of
      proteins. DESIGN AND METHODS: Degradation rates of short-lived proteins in
      neutrophils were measured in in vivo human model of elevated plasma Hcy and lower
      vitamin status and in animal model of Hcy added in vitro to rat neutrophils.
      RESULTS: In the human study, we found significant coefficients of correlation
      between plasma total homocysteine (tHcy) and the degradation rates of 21 protein
      fractions. In the animal model, Hcy significantly increased degradation rates of
      57 protein fractions. CONCLUSIONS: The increase in protein degradation rates,
      induced by Hcy, may provide a clue to our understanding of the mechanism of Hcy
      detrimental effects. Hcy may amplify the specific effect of cellular solutes on
      protein conformation, thereby monitor protein degradation rates to control enzyme
      activity. Consequently, the cell may lose its ability to maintain an efficient
      control of some crucial metabolic pathways, possibly leading to atherogenesis.

PMID- 15498530
TI  - Newborn screening for hepatorenal tyrosinemia by tandem mass spectrometry:
      analysis of succinylacetone extracted from dried blood spots.
AB  - OBJECTIVES: To develop a method for the determination of succinylacetone (SA) in
      dried blood spots (DBS) using tandem mass spectrometry (MS/MS). METHODS: SA was
      extracted from DBS with an acetonitrile and water solution (80:20 by volume)
      containing formic acid and hydrazine hydrate (both at 0.1% by volume), and
      analyzed by MS/MS with a total run time per sample under 2 min. The reference
      range for SA in newborns was determined by analyzing a control group of 3199 DBS.
      SA was also measured in stored newborn specimens from three patients diagnosed
      clinically with hepatorenal tyrosinemia (HT). RESULTS: The within-run precision
      was <or=7.4% and total precision was <or=12.2% on blood spots fortified with SA
      at 2, 10, and 50 micromol/L. The limit of quantitation was 1 micromol/L and the
      calibration was linear from 1 to 50 micromol/L. A comparison of SA analysis of
      this MS/MS method with an established enzyme assay indirectly quantitating SA by
      inhibition of delta-aminolevulinic acid dehydratase demonstrated a strong
      correlation. The reference range in the control group of unaffected newborn was
      determined to be <2 micromol/L, while SA in retrieved DBS from HT patients was
      significantly elevated, measuring 46.7, 36.5, and 23.2 micromol/L. CONCLUSIONS:
      We report a simple method that can be used for screening HT in newborns. Based on
      our limited experience, a 2 micromol/L cutoff could result in up to 100%
      sensitivity and specificity.

PMID- 15498531
TI  - Comparison of cyclosporine concentrations in renal transplant recipients using
      ACMIA and mFPIA methods.
AB  - OBJECTIVE: This study investigated the performance and data comparability of a
      new, relatively specific immunoassay method, affinity column mediated immunoassay
      (ACMIA) run on the Dimension Xpand-HM, and the established less specific
      monoclonal fluorescence polarization immunoassay (mFPIA) method on the TDx
      analyzer (mFPIA/TDx) in determining cyclosporine (CsA) concentrations. METHODS:
      Accuracy and within and between-run precision were tested. Then we measured CsA
      concentrations of 216 samples obtained from 51 patients and divided the 113
      samples from 21 patients with renal transplants into two groups based on sampling
      time. RESULTS: Accuracy relative to the four weighed-in concentrations ranged
      from 99% to 104% and from 106% to 117% for ACMIA and mFPIA/TDx, respectively. The
      mean within-run precision (CV%) for the ACMIA and mFPIA/TDx methods was 4.31% and
      2.57%, respectively. The mean recovery for ACMIA and mFPIA/TDx in the between-run
      study was 104.50% and 111.12%, respectively. The mFPIA/ACMIA ratio (the ratio of
      the concentration measured by mFPIA/TDx to that measured by ACMIA) of C2-3
      (concentrations measured 2-3 h after oral administration) was 118.85%, which was
      significantly smaller than that (139.12%) of C8-12 (those measured more than 8 h
      after the administration) at each mean concentration. CONCLUSIONS: These results
      indicate that ACMIA is more accurate than mFPIA/TDx, and the difference in the
      mFPIA/ACMIA ratio between C2-3 and C8-12 was due to the difference in the
      relative cross-reactivity with CsA metabolites. Although mFPIA/TDx had an
      apparent calibration error, both methods had a clinically acceptable within and
      between-run precision.

PMID- 15498532
TI  - The EMIT 2000 tacrolimus assay: an application protocol for the Beckman Synchron
      LX20 PRO analyzer.
AB  - OBJECTIVE: To develop and evaluate the performance of an application protocol for
      the EMIT 2000 tacrolimus (Tac) assay on the Beckman Synchron LX20 PRO Analyzer.
      DESIGN AND METHODS: Precision, accuracy, linearity, and lower limit of
      quantitation were investigated. Specimens from 212 kidney, liver, heart/heart
      lung, and islet cell transplant patients were analyzed and results were compared
      to those from the Abbott MEIA II assay. A separate population of 232 specimens
      was coanalyzed by the enzyme-multiplied immunoassay technique (EMIT) assay and
      liquid chromatography tandem mass spectrometry (LC-MS/MS). RESULTS: Total
      imprecision was 13.7% and 6.0% at concentrations of 3.4 and 19.1 microg/L,
      respectively. Recoveries from assayed reference materials ranged from 103% to
      109%. A quantitation range of 3.2-30.0 microg/L was validated. The EMIT assay on
      the LX20 PRO analyzer showed an average negative bias of 1% compared to the MEIA
      assay and an average positive bias of 17% compared to LC-MS/MS. CONCLUSION: This
      application for the EMIT 2000 Tac assay on the Beckman Synchron LX20 PRO analyzer
      enhances the versatility of the immunoassay for routine therapeutic drug
      monitoring (TDM) of this immunosuppressant in the clinical setting.

PMID- 15498533
TI  - Induced sputum in cystic fibrosis: within-week reproducibility of inflammatory
      markers.
AB  - Analysis of induced sputum has provided significant insight into the inflammatory
      response in chronic respiratory diseases such as asthma. The thick, tenacious
      nature of cystic fibrosis (CF) sputum presents certain challenges to such
      evaluation. We describe the development of a methodology to assess CF sputum, and
      the within-week reproducibility (to limit the possibility of any change in
      clinical status) of cellular and inflammatory markers. METHODS: Seventeen young
      adults [9 males, 8 females, mean age 24 (5), median (quartile range) years,
      percentage of predicted FEV(1) = 64.0 (18.0%)] with CF underwent sputum
      inductions on the Monday and Thursday of the same week. Patients were pretreated
      with 400 microg salbutamol and subsequently inhaled 5% saline via a breath
      enhanced nebulizer. Every 3-min nebulization was interrupted to allow for
      expectoration of sputum into a polypropylene pot. Sputum samples were dispersed
      with a solution of dithiothreitol (DTT) and deoxyribonuclease to allow for
      analysis of total cell count (TCC) and percentage neutrophils (%Neut).
      Measurement of tumor necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8), and
      neutrophil elastase was performed on samples dispersed with DTT alone. RESULTS:
      There were no significant differences between the measurements taken in the same
      week. Values for Day 1 versus Day 2 were as follows: TCC 20.8 (6.4) vs. 17.6
      (2.5) x 10(6) cells/ml; %Neut: 94.1 (0.0) vs. 95.4 (0.5) %; TNF-alpha 7.5 (26.0)
      vs. 21.0 (44.0) pg/ml; IL-8 610.0 (422.0) vs. 524.0 (587.0) ng/ml and neutrophil
      elastase 110.0 (19.75) vs. 49.75 (60.75) microM. High intraclass correlation
      coefficients (ICC) for TCC, %Neut, TNF-alpha IL-8 and neutrophil elastase were
      found (ICC = 0.76, 0.82, 0.93, 0.82, 0.74, respectively). CONCLUSIONS: The method
      developed here for the analysis of CF sputum shows good reproducibility and can
      be used to evaluate therapeutic interventions in patients with cystic fibrosis.

PMID- 15498534
TI  - ACE I allele and eNOS G allele crosstalk may have a role in chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Pulmonary hypertension, a characteristic of chronic obstructive
      pulmonary disease (COPD) has led us to investigate polymorphisms in angiotensin
      converting enzyme (ACE) and endothelial nitric oxide synthase (eNOS) genes.
      DESIGN AND METHODS: Sixty-six normal and 27 patients, all of whom were smokers,
      were screened for ACE Insertion/Deletion (I/D) and eNOS G894T and CA-repeat
      polymorphisms and for plasma ACE and NO levels. RESULTS: Elevated ACE and
      decreased NO levels were obtained with the pattern of II to ID to DD and GG to GT
      to TT conversion, respectively. Furthermore, the genotype combination of II and
      GG was significantly greater in controls as compared to patients (P = 0.01; OR =
      2.43; 95% CI: 1.21-4.87; RR = 2.00, 1.15-3.48). The CA-repeat multialleles showed
      a trimodal pattern in both the groups with a frequency range of 0.0057-0.103 and
      0.0208-0.1875 in the controls and patients, respectively. CONCLUSIONS: The lower
      ACE and higher NO levels by virtue of the interchromosomal interaction between
      the I and G alleles appear to cause less vasoconstriction and increase
      vasodilatation that may be advantageous in the improvement of the disease.

PMID- 15498536
TI  - Somatosensory processing in healthy newborns.
AB  - Attempting to understand more about somatosensory processing in newborns, we give
      an overview of somatosensory potential studies in preterm and term healthy
      newborns conducted during the past few decades. In addition, we present some of
      our recent data from somatosensory studies conducted with magnetoencephalography
      (MEG). The reviewed studies show maturational patterns of cortical responses to
      median and tibial nerve stimulation within the preterm-term period. In this era,
      maturation is reflected mainly as shortening of the latencies and increase in the
      amplitude of especially the early responses. However, the actual somatosensory
      processing beyond the latency and amplitude analysis has not been the goal in
      these studies. Although the somatosensory pathways and cortex are mature enough
      to produce the evoked responses, difficulties in measuring the neonatal responses
      with similar parameters as used for adults is suggested to reflect the special
      characteristics of newborn processing. Possible factors behind the
      inconsistencies between different newborn studies are discussed.

PMID- 15498537
TI  - Development of neurotransmitter systems during critical periods.
AB  - Neurotransmitters are released from neurons and mediate neuronal communication.
      Neuromodulators can also be released from other cells and influence the neuronal
      signaling. Both neurotransmitters and neuromodulators play an important role in
      the shaping and the wiring of the nervous system possibly during critical windows
      of the development. Monoamines are expressed in the very early embryo, at which
      stage the notochord already contains high noradrenaline levels. Purines and
      neuropeptides are probably also expressed at an early stage, in a similar way as
      they occur during early phylogenesis. The levels of most neurotransmitters and
      neuromodulators increase concomitantly with synapse formation. Some of them surge
      during the perinatal period (such as glutamate, catecholamines, and some
      neuropeptides) and then level off. The interesting question is to what extent the
      expression of neuroactive agents is related to the functional state of the fetus
      and the newborn. Monoamines are expressed in the very early embryo, at which
      stage the notochord already contains high noradrenaline levels. They may have an
      important role for neurotransmission in the fetus. In the adult mammal, the fast
      switching excitatory amino acids dominate. However, they also seem to be
      important for the wiring of the brain and the plasticity before birth. NMDA
      receptors that are supposed to mediate these effects dominate and are then
      substituted by AMPA receptors. The main inhibitory amino acids gamma-aminobutyric
      acid (GABA) and glycine are excitatory in the developing brain by depolarizing
      developing neurons that have high Cl- concentrations. This seems to be of major
      importance for the wiring of neuronal circuits. Prenatal or neonatal stress, for
      example, hypoxia, can affect the programming of neurotransmitter and receptor
      expression, which can lead to long-term behavioral effects.

PMID- 15498538
TI  - Initial experiences of performing fetal fMRI.

PMID- 15498539
TI  - Fetal magnetoencephalography: current progress and trends.
AB  - Multimodal testing is the key to successful fetal neurological assessment. New
      mutichannel SQUID (Superconducting Quantum Interference Device) sensor devices
      can now be used to effectively record fetal auditory evoked responses (fAER) and
      visual evoked responses (VER), spontaneous brain activity, and heart activity. In
      this paper, we review the current progress in the area of fetal
      magnetoencephalography (fMEG) and also present an overview of the studies
      performed using a system called SARA that is specifically designed for fetal MEG
      studies. With the capability of recording spontaneous and evoked magnetic fields,
      we believe the monitoring of the neurological status of the fetus can be
      effectively implemented and can encourage the development of new strategies of
      intervention for the high-risk fetus.

PMID- 15498540
TI  - Spontaneous neuronal activity in fetuses and newborns.
AB  - We compared the magnetic cerebral activity of 10 fetal subjects at two different
      gestational ages. Spontaneous cerebral activity was recorded with a large array
      magnetometer specially designed to conform to the maternal gravid abdomen during
      the third trimester of pregnancy. We recorded each fetal subject at least twice:
      first at less than 36 weeks and again after 36 weeks gestational age. Pervasive
      signal artifacts of maternal magnetocardiogram (MCG), respiration, uterine wall
      contractions, and fetal magnetocardiogram were removed with special filtering
      that preserved fetal cerebral signals. We used ultrasound to locate the fetal
      head immediately before and after the magnetic recordings. Auditory and visual
      evoked responses were also recorded for each fetal subject. The calculated origin
      for the spontaneous cerebral signals was verified to be at the ultrasound
      location for the fetal head and to be similar to the calculated locations for the
      cerebral evoked responses. The recordings for each fetal subject at less than and
      greater than 36 weeks gestational age were compared to the expected EEG findings
      for premature infants at comparable post conceptual ages.

PMID- 15498541
TI  - Magnetoencephalography is feasible for infant assessment of auditory
      discrimination.
AB  - Magnetoencephalography (MEG) detects the brain's magnetic fields as generated by
      neuronal electric currents arising from synaptic ion flow. It is noninvasive, has
      excellent temporal resolution, and it can localize neuronal activity with good
      precision. For these reasons, many scientists interested in the localization of
      brain functions have turned to MEG. The technique, however, is not without its
      drawbacks. Those reluctant to employ it cite its relative awkwardness among
      pediatric populations because MEG requires subjects to be fairly still during
      experiments. Due to these methodological challenges, infant MEG studies are not
      commonly pursued. In the present study, MEG was employed to study auditory
      discrimination in infants. We had two goals: first, to determine whether reliable
      results could be obtained from infants despite their movements; and second, to
      improve MEG data analysis methods. To get more reliable results from infants we
      employed novel hardware (real-time head-position tracking system) and software
      (signal space separation method, SSS) solutions to better deal with noise and
      movement. With these solutions, the location and orientation of the head can be
      tracked in real time and we were able to reduce noise and artifacts originating
      outside the helmet significantly. In the present study, these new methods were
      used to study the biomagnetic equivalents of event-related potentials (ERPs) in
      response to duration changes in harmonic tones in sleeping, healthy, full-term
      newborns. Our findings indicate that with the use of these new analysis routines,
      MEG will prove to be a very useful and more accessible experimental technique
      among pediatric populations.

PMID- 15498542
TI  - Functional development of the visual system in human fetus using
      magnetoencephalography.
AB  - The development of the human brain in utero is normally regarded as a dynamic
      process involving mainly structural and quantitative changes in neurons and their
      distribution. However, it is generally accepted that a parallel development of
      functional specialization occurs in certain areas of the brain, especially in the
      primary cortex. Nearly all knowledge of functional fetal brain development has
      been obtained from various animal studies rather than human studies. These
      studies show that the primary sensory areas like auditory, visual, and
      somatosensory cortex show a basic function similar to that of a fully developed
      brain. It has been specifically shown that the visual system develops during
      fetal life and becomes functional before birth. Several studies have demonstrated
      the feasibility of using visual evoked response (VER) recordings on preterm human
      infants to follow the functional development of the visual system. With the
      advent of the noninvasive technique of magnetoencephalography (MEG), human fetal
      VER recordings are now possible thus providing the opportunity to track its
      functional development with gestation. We present and discuss the results of VER
      recordings in human fetuses starting at 28 weeks of gestation performed using a
      151-channel MEG system.

PMID- 15498543
TI  - Developmental changes of auditory-evoked fields in fetuses.
AB  - Fetal magnetoencephalography (fMEG) could be a viable noninvasive tool to
      investigate the development of neuronal functioning in the unborn by means of the
      maturation of cortical auditory-evoked fields (CAEF). The earliest successful
      recording of a CAEF component was performed at the gestational age of 27
      completed weeks with an observed peak latency of 294 ms. Several different
      components could be differentiated in the CAEF complex. They were classified in
      accordance with a nomenclature introduced for cortical auditory-evoked potential
      (AEP) components in preterm neonates. During the third trimester of pregnancy,
      the detection of any component was successful in 77% of the cases. The detection
      rates for the different components observed were P1pm 31%; N1pm 21%; P2pm 27%;
      N2pm 39%; and P3pm 27%. The development of fetal CAEF is described both
      intraindividually in longitudinal observations and interindividually by grouped
      comparison throughout the second half of the pregnancy in the largest series of
      subjects in the literature. The components P2pm and N2pm show a significant
      negative correlation of their peak latencies with increasing gestational age (P <
      0.05). fMEG allows to observe the development of a parameter of prenatal cortical
      function that can be interpreted as maturation. The results are in good
      accordance with those obtained in newborn EEG studies in preterm neonates.

PMID- 15498544
TI  - Assessment of fetal neurodevelopment via fetal magnetocardiography.
AB  - Fetal magnetocardiography (fMCG) offers unique capabilities for assessment of
      fetal heart rate (FHR) and fetal behavior, which are fundamental aspects of
      neurodevelopment. The most important attribute of fMCG for FHR monitoring is its
      high precision, which allows accurate assessment of beat-to-beat fetal heart rate
      variability (FHRV), including respiratory sinus arrhythmia. Using mathematical
      indices to assess FHRV, we find that short- and long-term FHRV both increase
      during gestation but not in the same manner. The largest increases in short-term
      FHRV occur during the last trimester, while the largest increases in long-term
      FHRV occur early on, with smaller changes occurring during the last trimester.
      The fMCG also allows assessment of fetal activity. This results from the high
      sensitivity of the signal to the position and orientation of the fetal heart.
      FMCG actograms are therefore specific for fetal trunk movement, which are thought
      to be more important than isolated extremity movements and other small fetal
      movements. The ability to assess FHR, FHRV, and fetal trunk movement
      simultaneously makes fMCG a valuable tool for neurodevelopment research.

PMID- 15498545
TI  - Electrographic imaging of recognition memory in 34-38 week gestation intrauterine
      growth restricted newborns.
AB  - Electrophysiological imaging of recognition memory using event-related potentials
      (ERPs) in intrauterine growth-restricted (IUGR) newborns allows assessment of
      recognition memory before the onset of multiple confounding variables. Animal
      models that reproduce the physiologic components associated with IUGR have
      demonstrated adverse effects on the hippocampus, a structure that is essential to
      normal memory processing. Previous electrophysiologic studies have demonstrated
      shortened auditory-evoked potential (AEP) and visual-evoked potential (VEP)
      latencies in IUGR infants suggesting accelerated neural maturation in response to
      the adverse in-utero environment. The hypothesis of the current study was that
      newborns with IUGR and head-sparing would demonstrate altered auditory
      recognition memory when compared to controls and that the configuration of the
      alteration would evidence advanced maturation but still be different from that of
      typically grown newborns. Twelve IUGR newborns born at 34-38 weeks gestation with
      head-sparing and 16 age-matched control newborns were tested with both a
      speech/nonspeech paradigm to assess auditory sensory processing and a novel
      (stranger's voice) and familiar (mother's voice) paradigm to assess recognition
      memory. In the recognition memory experiment, a three-way interaction of
      condition, lead, and group was identified for the lateral leads T4, CM3, and CM4
      with the response to the mother being of much greater area in the IUGR cohort
      than in the controls. This ERP configuration has previously been reported for the
      midline leads in term newborns. The findings indicate that IUGR newborns with
      head-sparing have electrophysiologic evidence of accelerated maturation of
      cognitive processing suggesting an atypical process of maturation that may not
      support typical cognitive development.

PMID- 15498546
TI  - Imaging of early brain injury and cortical plasticity.
AB  - The human brain undergoes complex organizational changes during development in
      and ex utero. Pathogenic events affecting the developing brain cause
      abnormalities or lesions, the patterns of which depend on the stage of brain
      development. During the first and second trimester, cortical neurogenesis
      predominantly takes place, characterized by proliferation, migration, and
      organization of neuronal cells. Brain pathology is characterized by
      maldevelopments. During the third trimester, growth and differentiation events
      are predominant, which persist into postnatal life. Disturbances of brain
      development during this period mainly cause lesions. During the early third
      trimester, periventricular white matter is especially affected, whereas toward
      the end of the third trimester, gray matter, either cortical or deep gray matter,
      appears to be more vulnerable. These patterns of brain maldevelopments or lesions
      offer excellent models to study mechanisms of organization and reorganization in
      the developing brain. Evidence for superior brain plasticity is well established
      for language function after early left-sided lesions. Some evidence exists for
      higher compensatory potential within in the motor system; maintenance of
      ipsilateral tracts seems to play a certain, but only incomplete functional role
      after unilateral lesions in early and mid gestation. The visual system seems to
      have limited compensatory potential.

PMID- 15498547
TI  - Maturational effects on newborn ERPs measured in the mismatch negativity
      paradigm.
AB  - The mismatch negativity (MMN) component of event-related potentials (ERPs), a
      measure of passive change detection, is suggested to develop early in comparison
      to other ERP components, and an MMN-like response has been measured even from
      preterm infants. The MMN response in adults is negative in polarity at about 150
      200 ms. However, the response measured in a typical MMN paradigm can also be
      markedly different in newborns, even opposite in polarity. This has been
      suggested to be related to maturational factors. To verify that suggestion, we
      measured ERPs of 21 newborns during quiet sleep to rarely occurring deviant tones
      of 1100 Hz (probability 12%) embedded among repeated standard tones of 1000 Hz in
      an oddball sequence. Gestational age (GA) and two cardiac measures, vagal tone
      (V) and heart period (HP), were used as measures of maturation. GA and HP
      explained between 36% and 42% of the total variance of the individual ERP peak
      amplitude (the largest deflection of the difference wave at a time window of 150
      375 ms) at different scalp locations. In the discriminant function analyses, GA
      and HP as classifying variables differentiated infants in whom the peak of the
      difference wave had positive polarity from those with a negative polarity at an
      accuracy level ranging from 72% to 91%. These results demonstrate that during
      quiet sleep, maturational factors explain a significant portion of the ERP
      difference wave amplitude in terms of its polarity, indicating that the more
      mature the ERPs are, the more positive the amplitude. The present study suggests
      that maturational effects should be taken into account in ERP measurements using
      MMN paradigms with young infants.

PMID- 15498548
TI  - Letting go.

PMID- 15498549
TI  - Structure prediction, evolution and ligand interaction of CHASE domain.
AB  - Cytokinins are plant hormones involved in the essential processes of plant growth
      and development. They bind with receptors known as CRE1/WOL/AHK4, AHK2, and AHK3,
      which possess histidine kinase activity. Recently, the sensor domain
      cyclases/histidine kinases associated sensory extracellular (CHASE) was
      identified in those proteins but little is known about its structure and
      interaction with ligands. Distant homology detection methods developed in our
      laboratory and molecular phylogeny enabled the prediction of the structure of the
      CHASE domain as similar to the photoactive yellow protein-like sensor domain. We
      have identified the active site pocket and amino acids that are involved in
      receptor-ligand interactions. We also show that fold evolution of cytokinin
      receptors is very important for a full understanding of the signal transduction
      mechanism in plants.

PMID- 15498551
TI  - Fourier transform infrared microspectroscopy as a new tool for nematode studies.
AB  - We report the results of a microspectroscopy study on the Fourier transform
      infrared (FT-IR) absorption spectra of Caenorhabditis elegans, collected from the
      different parts of a single intact specimen--pharynx, intestine and tail regions.
      The principal absorption bands were assigned to the molecular species present in
      C. elegans, with an excellent reproducibility for the pharynx spectrum. These
      results enabled us to explore if FT-IR microspectroscopy could offer a new tool
      for nematode identification. As an example, the discrimination among four well
      characterised nematode taxa is reported. The FT-IR results completely match those
      obtained by Blaxter and colleagues through molecular biology [Nature 392 (1998)
      71].

PMID- 15498550
TI  - Molecular cloning in yeast by in vivo homologous recombination of the yeast
      putative alpha1 subunit of the voltage-gated calcium channel.
AB  - Saccharomyces cerevisiae has only one gene encoding a putative voltage-gated Ca2+
      channel pore-forming subunit, CCH1, which is not possible to be cloned by
      conventional molecular cloning techniques using Escherichia coli. Here, we report
      the successful cloning of CCH1 in yeast by in vivo homologous recombination
      without using E. coli. Overexpression of the cloned CCH1 or MID1 alone, which
      encodes a putative stretch-activated Ca2+ channel component, does not increase
      Ca2+ uptake activity, but co-overexpression results in a 2- to 3-fold increase.
      Overexpression of CCH1 does not substantially complement the lethality and low
      Ca2+ uptake activity of a mid1 mutant and vice versa. These results indicate that
      co-overproduction of Cch1 and Mid1 is sufficient to increase Ca2+ uptake
      activity.

PMID- 15498552
TI  - Medical implications from the crystal structure of a copper-containing amine
      oxidase complexed with the antidepressant drug tranylcypromine.
AB  - The X-ray crystal structure of the copper-containing quinoprotein amine oxidase
      from E. coli has been determined in complex with the antidepressant drug
      tranylcypromine to 2.4 A resolution. The drug is a racemic mix of two
      enantiomers, but only one is seen bound to the enzyme. The other enantiomer is
      not acting as a substrate for the enzyme as no catalytic activity was detected
      when the enzyme was initially exposed to the drug. The inhibition of human copper
      amine oxidases could be a source of side-effects in its use as an antidepressant
      to inhibit the flavin-containing monoamine oxidases in the brain.

PMID- 15498553
TI  - Overexpression of AtHMA4 enhances root-to-shoot translocation of zinc and cadmium
      and plant metal tolerance.
AB  - AtHMA4 is an Arabidopsis thaliana P1B-ATPase which transports Zn and Cd. Here, we
      demonstrate that AtHMA4 is localized at the plasma membrane and expressed in
      tissues surrounding the root vascular vessels. The ectopic overexpression of
      AtHMA4 improved the root growth in the presence of toxic concentrations of Zn, Cd
      and Co. A null mutant exhibited a lower translocation of Zn and Cd from the roots
      to shoot. In contrast, the AtHMA4 overexpressing lines displayed an increase in
      the zinc and cadmium shoot content. Altogether, these results strongly indicate
      that AtHMA4 plays a role in metal loading in the xylem.

PMID- 15498554
TI  - Conformational stability of amyloid fibrils of beta2-microglobulin probed by
      guanidine-hydrochloride-induced unfolding.
AB  - Although the stability of globular proteins has been studied extensively, that of
      amyloid fibrils is scarcely characterized. Beta2-microglobulin (beta2-m) is a
      major component of the amyloid fibrils observed in patients with dialysis-related
      amyloidosis. We studied the effects of guanidine hydrochloride on the amyloid
      fibrils of beta2-m, revealing a cooperative unfolding transition similar to that
      of the native state. The stability of amyloid fibrils increased on the addition
      of ammonium sulfate, consistent with a role of hydrophobic interactions. The
      results indicate that the analysis of unfolding transition is useful to obtain
      insight into the structural stability of amyloid fibrils.

PMID- 15498555
TI  - Identification of genes regulated by oleic acid in Jurkat cells by suppressive
      subtractive hybridization analysis.
AB  - In this study, the effect of oleic acid (50 microM) on gene expression of Jurkat
      cells (human T lymphocytes cell line) was examined using the suppressive
      subtractive hybridization approach. This technique allowed us to identify genes
      with higher or lower expression after cell treatment with oleic acid as compared
      to untreated cells. Oleic acid upregulated the expression of the translation
      elongation factor alpha 1 and ATP synthase 8 and downregulated gp96 (human tumor
      rejection antigen gp96), heat-shock protein 60 and subtilisin-like protein 4.
      These results suggest that oleic acid, at plasma physiological concentration, can
      regulate the expression of important genes to maintain the machinery that ensures
      cell functioning.

PMID- 15498556
TI  - Characterization of SARS-CoV main protease and identification of biologically
      active small molecule inhibitors using a continuous fluorescence-based assay.
AB  - Severe acute respiratory syndrome associated coronavirus main protease (SARS-CoV
      Mpro) has been proposed as a prime target for anti-SARS drug development. We have
      cloned and overexpressed the SARS-CoV Mpro in Escherichia coli, and purified the
      recombinant Mpro to homogeneity. The kinetic parameters of the recombinant SARS
      CoV Mpro were characterized by high performance liquid chromatography-based assay
      and continuous fluorescence-based assay. Two novel small molecule inhibitors of
      the SARS-CoV Mpro were identified by high-throughput screening using an
      internally quenched fluorogenic substrate. The identified inhibitors have Ki
      values at low microM range with comparable anti-SARS-CoV activity in cell-based
      assays.

PMID- 15498557
TI  - GalNAc pretreatment inhibits trapping of Bacillus thuringiensis Cry1Ac on the
      peritrophic membrane of Bombyx mori.
AB  - Bombyx mori (ShunreixShogetsu) is sensitive to Cry1Aa and resistant to Cry1Ac,
      both insecticidal proteins of Bacillus thuringiensis. Cry1Aa passed through the
      peritrophic membrane (PM) much faster (0.37 microg/mm2 PM/h) than Cry1Ac (0.05
      microg/mm2 PM/h) during the initial observation period. Both Cry1Aa and Cry1Ac
      bound to the PM but only the binding of Cry1Ac was specifically inhibited by N
      acetylgalactosamine (GalNAc). When Cry1Ac was pretreated with GalNAc, Cry1Ac
      permeated the PM much faster. These results suggested that Cry1Ac bound a PM
      protein via GalNAc on a sugar side chain. The role of the PM on Cry1Ac resistance
      of B. mori was briefly discussed.

PMID- 15498558
TI  - A novel method of analyzing proline synonymous codons in E. coli.
AB  - Proline is a special imino acid in protein and the isomerization of the prolyl
      peptide bond has notable biological significance and influences the final
      structure of protein greatly, so the correlation between proline synonymous codon
      usage and local amino acid, the correlation between proline synonymous codon
      usage and the isomerization of the prolyl peptide bond were both investigated in
      the Escherichia coli genome by using a novel method based on information theory.
      The results show that in peptide chain, the residue at the first position C
      terminal influences the usage of proline synonymous codon greatly and proline
      synonymous codons contain some factors influencing the isomerization of the
      prolyl peptide bond.

PMID- 15498559
TI  - Thyroid hormone potentiates glucocorticoid-evoked airway Na+ transport without
      affecting alpha-ENaC transcription.
AB  - Glucocorticoid and thyroid hormones (T3) are important for the development of the
      lungs' Na+ absorbing phenotype, which is essential for the integrated functioning
      of the respiratory tract. Electrometric studies of H441 airway epithelial cells
      confirmed that dexamethasone increases apical Na+ conductance (GNa) and
      demonstrated that T3 facilitates this control over GNa. Assays of transcriptional
      activity showed that dexamethasone caused concentration-dependent activation of
      the human alpha-ENaC promoter (EC50 approximately 5 nM) but, despite its clear
      effect on GNa, T2 had no effect upon the transcriptional response to
      dexamethasone. The facilitation of Na+ transport may thus reflect control over
      events downstream to transcription.

PMID- 15498560
TI  - The C-terminal 26-residue peptide of serpin A1 stimulates proliferation of breast
      and liver cancer cells: role of protein kinase C and CD47.
AB  - C26, the C-terminal 26 residue peptide of serpin A1, significantly increased cell
      proliferation in cultures of hepatoma cells, but not in porcine kidney epithelial
      cells, human skin fibroblasts or keratinocytes. The mitogenic activity of C26 was
      preferentially inhibited with a protein kinase C (PKC) inhibitor, an antibody
      against CD47 and CD47 short interfering RNA. The mutant C26-K19R,N22M, imitating
      a thrombospondin-like cell adhesion motif, increased the mitogenic activity in
      both Hep G2 cells and MCF-7 breast cancer cells. Phosphorylation of C26 at T24 (a
      putative PKC phosphorylation site) resulted in a 1.9-2.5 increase in mitogenic
      activity over C26 in MCF-7 cells.

PMID- 15498561
TI  - Reduced amino acid alphabet is sufficient to accurately recognize intrinsically
      disordered protein.
AB  - Intrinsically disordered proteins are an important class of proteins with unique
      functions and properties. Here, we have applied a support vector machine (SVM)
      trained on naturally occurring disordered and ordered proteins to examine the
      contribution of various parameters (vectors) to recognizing proteins that contain
      disordered regions. We find that a SVM that incorporates only amino acid
      composition has a recognition accuracy of 87+/-2%. This result suggests that
      composition alone is sufficient to accurately recognize disorder. Interestingly,
      SVMs using reduced sets of amino acids based on chemical similarity preserve high
      recognition accuracy. A set as small as four retains an accuracy of 84+/-2%; this
      suggests that general physicochemical properties rather than specific amino acids
      are important factors contributing to protein disorder.

PMID- 15498562
TI  - Mutation of the small acidic tract A1 drastically reduces nucleoplasmin activity.
AB  - Xenopus laevis nucleoplasmin is a molecular chaperone that mediates sperm
      decondensation and nucleosome assembly. Nucleoplasmin has three acidic tracts
      (A1, A2 and A3) and until recent years the long polyglutamic tract A2 was thought
      to be the binding site for basic proteins. However, the latest publications in
      this field show that neither A2 nor A3 is indispensable for histone and sperm
      specific protein binding. In this work, we show that the mutation of only four
      acidic amino acid residues of the small A1 tract drastically reduces
      nucleoplasmin decondensing activity, pointing out this region as the potential
      binding site for sperm proteins.

PMID- 15498563
TI  - The SEP domain of p47 acts as a reversible competitive inhibitor of cathepsin L.
AB  - The solution structure of the human p47 SEP domain in a construct comprising
      residues G1-S2-p47(171-270) was determined by NMR spectroscopy. A structure
      derived hypothesis about the domains' function was formulated and pursued in
      binding experiments with cysteine proteases. The SEP domain was found to be a
      reversible competitive inhibitor of cathepsin L with a Ki of 1.5 microM. The
      binding of G1-S2-p47(171-270) to cathepsin L was mapped by biochemical assays and
      the binding interface was investigated by NMR chemical shift perturbation
      experiments.

PMID- 15498564
TI  - Mutation E46K increases phospholipid binding and assembly into filaments of human
      alpha-synuclein.
AB  - Missense mutations (A30P and A53T) in alpha-synuclein and the overproduction of
      the wild-type protein cause familial forms of Parkinson's disease and dementia
      with Lewy bodies. Alpha-synuclein is the major component of the filamentous Lewy
      bodies and Lewy neurites that define these diseases at a neuropathological level.
      Recently, a third missense mutation (E46K) in alpha-synuclein was described in an
      inherited form of dementia with Lewy bodies. Here, we have investigated the
      functional effects of this novel mutation on phospholipid binding and filament
      assembly of alpha-synuclein. When compared to the wild-type protein, the E46K
      mutation caused a significantly increased ability of alpha-synuclein to bind to
      negatively charged liposomes, unlike the previously described mutations. The E46K
      mutation increased the rate of filament assembly to the same extent as the A53T
      mutation. Filaments formed from E46K alpha-synuclein often had a twisted
      morphology with a cross-over spacing of 43 nm. The observed effects on lipid
      binding and filament assembly may explain the pathogenic nature of the E46K
      mutation in alpha-synuclein.

PMID- 15498565
TI  - Suppression of P-glycoprotein gene expression in Hs578T/Dox by the overexpression
      of caveolin-1.
AB  - Caveolin-1, the principal component of caveolae, is a 21-24 kDa integral membrane
      protein. The interaction of the caveolin-1 scaffolding domain with signaling
      molecules can functionally inhibit the activity of these signaling proteins.
      Little is known about how caveolin-1 influences the expression of P-glycoprotein
      (P-gp), an ABC transporter encoded by multi-drug resistance (MDR1) gene. To
      elucidate the possible mechanism between caveolin-1 and P-gp expression, in the
      present study, we overexpressed caveolin-1 in the Hs578T/Dox breast
      adenocarcinoma cells, a multidrug resistant line, and then selected single clone
      cells highly expressing caveolin-1 level. Both Western blot and confocal
      microscopy analyses showed that caveolin-1 was markedly overexpressed in the
      transfectants, while P-gp protein was almost abolished. Reverse transcription
      polymerase chain reaction also showed that the expression of P-gp mRNA was
      significantly suppressed in the transfectants. It was confirmed further by
      Northern blot analysis. Moreover, through measuring the changes of drug
      resistance and P-gp transport activity in the transfectants, we found that
      overexpression of caveolin-1 reversed drug resistance of transfectants and
      lowered their P-gp transport activity to the level of Hs578T/S. Taken together,
      our results indicate that such suppression of P-gp in the transfectants
      overexpressing caveolin-1 may occur at the transcriptional level.

PMID- 15498566
TI  - A single in vivo-selected point mutation in the active center of Toxoplasma
      gondii ferredoxin-NADP+ reductase leads to an inactive enzyme with greatly
      enhanced affinity for ferredoxin.
AB  - Electron transfer between plant-type [2Fe-2S] ferredoxin (Fd) and ferredoxin
      NADP+ reductase (FNR) depends on the physical interaction between both proteins.
      We have applied a random mutagenesis approach with subsequent in vivo selection
      using the yeast two-hybrid system to obtain mutants of Toxoplasma gondii FNR with
      higher affinity for Fd. One mutant showed a 10-fold enhanced binding using
      affinity chromatography on immobilized Fd. A single serine-to-arginine exchange
      in the active site was responsible for its increased affinity. The mutant
      reductase was also enzymatically inactive. Homology modeling of the mutant FNR-Fd
      complex predicts substantial alterations of protein-FAD interactions in the
      active site of the enzyme with subsequent structural changes. Collectively, for
      the first time a point mutation in this important class of enzymes is described
      which leads to greatly enhanced affinity for its protein ligand.

PMID- 15498567
TI  - Role of the C-terminal region of mouse inducible Hsp72 in the recognition of
      peptide substrate for chaperone activity.
AB  - Here, we produced the C-terminal truncation variants of mouse inducible heat
      shock protein 72 (Hsp72) to elucidate the regulatory role of the C-terminal
      helical lid of Hsp70 for substrate recognition. All of the truncation variants
      containing the substrate binding domain bound a short-length peptide substrate
      CLLLSAPRR. When a large mass reduced carboxymethyl alpha-lactalbumin (RCMLA) as a
      substrate was used in gel filtration experiment, we observed the complex
      formation only for the truncation variants containing the long alpha-helix C in
      the helical lid. However, RCMLA binding occurred even for the variants lacking
      alpha-helix C when their C-terminal region was anchored onto a solid phase.
      Together with the finding that helix C is involved in the self-association of
      Hsp70, our present data suggest that the C-terminal region of Hsp70 modulates the
      substrate recognition and its kinetics may be substrate-mass dependent.

PMID- 15498568
TI  - Expression of a cascading genetic network within liposomes.
AB  - Liposomes have long been used as possible compartments for artificial cells, and
      it has been shown that liposomes can sustain various types of biochemical
      reactions. To elevate the degree of molecular complexity of the system in
      liposomes, we have constructed a two-stage genetic network encapsulated in
      liposomes. This two-stage genetic network was constructed with the plasmid pTH,
      in which the protein product of the first stage (T7 RNA polymerase) is required
      to drive the protein synthesis of the second stage (GFP). We show that the two
      stage genetic network constructed in a cell-free expression system is functional
      within liposomes.

PMID- 15498570
TI  - N-glycosylation is required for efficient secretion of a novel human secreted
      glycoprotein, hPAP21.
AB  - The present study reported the isolation and characterization of a novel human
      secreted protein, named as hPAP21 (human protease-associated domain-containing
      protein, 21 kDa), encoded by the hypothetical gene chromosome 2 open reading
      frame 7 (C2orf7) that contains signal peptide in its N-terminus, without
      transmembrane domain, except for PA domain in its middle. Western blotting assay
      indicated that the c-Myc tagged hPAP21 could be secreted into culture medium in
      the transfected Chinese hamster ovary cells. However, the molecular weights,
      whatever intracellular (28 kDa) or extracellular (30 kDa) forms, are larger than
      that of the prediction. To define whether the glycosylation was important process
      for its secretion, endoglycosidase H (Endo H) and PNGase F (PNG F) were employed
      to evaluate the effect of glycosylation types on secretion of hPAP21.
      Interestingly, the extracellular forms were primarily sensitive to PNG F, not
      Endo H, implying that complex N-glycosylation could be required for the secretion
      of hPAP21. Furthermore, N-glycosylation of Asn171 was confirmed as potential
      crucial process for the secretory protein via site-directed mutagenesis assay.
      All data will be contributed to the understanding of molecular functions of
      hPAP21.

PMID- 15498569
TI  - Proteoglycan isolated from Phellinus linteus inhibits tumor growth through
      mechanisms leading to an activation of CD11c+CD8+ DC and type I helper T cell
      dominant immune state.
AB  - Dendritic cells (DC) are known to not only induce the activation of T cells, but
      are also associated with the polarization of T cells. This study investigated
      whether or not proteoglycan (PG) isolated from Phellinus linteus induces the
      phenotypic and functional maturation of CD11c+ DC in vitro and in vivo. PG was
      found to induce the phenotypic and functional maturation of bone marrow-derived
      DC via Toll-like receptors (TLR) 2 and 4 in vitro. Administration of PG in vivo
      strongly inhibited the MCA-102 tumor growth and increase in vivo. The ratio of
      CD8+ DC to CD8- DC increased, and PG enhanced IL-12 and IFN-gamma production, and
      expression of surface molecules including major histocompatibility complexes
      (MHC) classes I, MHC II, CD80, and CD86 in MCA-102-challenged mice. PG also
      caused a marked increase in the production of Th (helper T cells)-1 cytokine (IFN
      gamma) and a decrease in the production of Th-2 cytokine (IL-4) by splenic cells
      and inguinal lymph node cells in MCA-102 tumor-bearing mice. Furthermore, PG
      stimulated the proliferation of CD4+ and CD8+ T cells. In addition, a combination
      of PG and tumor lysate-pulsed DC inhibited completely the growth of MCA-102 cells
      in tumor-bearing mice. These results indicate that the administration of PG
      inhibited the tumor growth through a mechanism leading to a Th-1 dominant immune
      state and the activation of CD11cCD8+ DC.

PMID- 15498571
TI  - A kunitz-type protease inhibitor bikunin disrupts ligand-induced oligomerization
      of receptors for transforming growth factor (TGF)-beta and subsequently
      suppresses TGF-beta signalings.
AB  - We previously found that bikunin (bik), a Kunitz-type protease inhibitor,
      suppresses transforming growth factor-beta1 (TGF-beta1)-stimulated expression of
      urokinase-type plasminogen activator (uPA) in human ovarian cancer cells that
      lack endogenous bik. In the present study, we tried to elucidate the mechanism by
      which bik also inhibits plasminogen activator inhibitor type-1 (PAI-1) and
      collagen synthesis using human ovarian cancer cells. Here, we show that (a) there
      was an enhanced production of both uPA and PAI-1 in HRA cells in response to TGF
      beta1; (b) the overexpression of bik in the cells or exogenous bik results in the
      inhibition of TGF-beta1 signaling as measured by phosphorylation of the
      downstream signaling effector Smad2, nuclear translocation of Smad3, and
      production of PAI-1 and collagen; (c) bik neither decreased expression of TGF
      beta receptors (TbetaRI and TbetaRII) in either cell types nor altered the
      specific binding of 125I TGF-beta1 to the cells, indicating that the effects of
      bik in these cells are not mediated by ligand sequestration; (d) TbetaRI and
      TbetaRII present on the same cells exclusively form aggregates in TGF-beta1
      stimulated cells; (e) co-treatment of TGF-beta1-stimulated cells with bik
      suppresses TGF-beta1-induced complex formation of TbetaRI and TbetaRII; and (f) a
      chondroitin-4-sulfate side chain-deleted bik (deglycosylated bik) does not
      inhibit TGF-beta1 signaling or association of type I/type II receptor. We
      conclude that glycosylated bik attenuates TGF-beta1-elicited signaling cascades
      in cells possibly by abrogating the coupling between TbetaRI and TbetaRII and
      that this probably provides the mechanism for the suppression of uPA and PAI-1
      expression.

PMID- 15498572
TI  - Membrane-permeabilizing motif in Semliki forest virus E1 glycoprotein.
AB  - Cell infection by alphaviruses is accompanied by membrane permeability changes.
      New predictive approaches, including the computation of interfacial affinity and
      corresponding hydrophobic moments, suggest a segmented amphipathic-at-interface
      domain in the stem region of Semliki Forest virus fusion protein E1. Expression
      of E1 sequences in Escherichia coli cells confirmed that the membrane proximal
      plus transmembrane (TM) domain unit permeabilizes cells as efficiently as the 6K
      viroporin. Both our predictive and experimental data support the involvement of
      the E1 stem-TM region in membrane insertion and permeabilization. We propose to
      combine Wimley-White hydrophobicity analysis with expression-coupled permeability
      assays in order to identify viral products implied in breaching cell membrane
      barriers during infection.

PMID- 15498573
TI  - Transcriptomic responses to cadmium in the ectomycorrhizal fungus Paxillus
      involutus.
AB  - The molecular mechanisms underlying the response of ectomycorrhizal fungi to
      heavy metals in general and cadmium in particular remain poorly understood. We
      screened 2040 arrayed cDNAs of the ectomycorrhizal fungus Paxillus involutus to
      identify cadmium-responsive genes by using differential hybridization. Forty nine
      (2.4%) of the 2040 cDNAs were differentially expressed, among which transcripts
      coding a laccase, an aconitase, and a metallothionein were upregulated by 3.9-,
      3.7- and 2.8-fold, respectively, whereas genes coding hydrophobins and threonine
      dehydratase were strongly downregulated. Our results suggest that complexation of
      cadmium by phenolic compounds, or by complexing peptides such as
      metallothioneins, is probably key determinant of the cellular response to cadmium
      in P. involutus. In addition, the present study suggests that the synthesis of
      hydrophobins may be efficiently reduced, thus redirecting Cys to the manufacture
      of Cys-enriched compounds.

PMID- 15498574
TI  - Dual signaling by mGluR5a results in bi-directional modulation of N-type Ca2+
      channels.
AB  - We have studied how N-type Ca2+ channels are modulated by the metabotropic
      glutamate receptor 5a (mGluR5a) in Xenopus oocytes. Stimulation of the receptor
      with glutamate initiated two parallel responses, a rapid inhibition followed by
      an upregulation of the Ca2+ current. Although a subsequent stimulation did not
      upregulate the Ca2+ current, it did still produce a reduction in the amplitude of
      the current. The upregulation of Ca2+ channels was prevented by the protein
      kinases inhibitor staurosporine and it was mimicked by the activation of PKC with
      phorbol esters. In contrast, the inhibition of the Ca2+ current was insensitive
      to staurosporine. These results show that mGluR5a exerts a bi-directional
      influence on Ca2+ channels, which may explain how group I mGluRs facilitate and
      inhibit glutamate release at central synapses.

PMID- 15498575
TI  - Sizing the pore of the volume-sensitive anion channel by differential polymer
      partitioning.
AB  - Partitioning of ethylene glycol and its polymeric forms into the pore of the
      volume-sensitive outwardly rectifying (VSOR) anion channel was studied to assess
      the pore size. Polyethylene glycol (PEG) PEG 200-300 (Rh = 0.27-0.53 nm)
      effectively suppressed the single-channel currents, whereas PEG 400-4000 (Rh =
      0.62-1.91 nm) had little or no effect. Since all the molecules tested effectively
      decreased electric conductivity of the bulk solution, the observed differential
      effects between PEG 200-300 and PEG 400-4000 on the VSOR single-channel current
      are due to their limited partitioning into the channel lumen. The cut-off radius
      of the VSOR channel pore was assessed to be 0.63 nm.

PMID- 15498576
TI  - Interaction of rat poly(A)-binding protein with poly(A)- and non-poly(A)
      sequences is preferentially mediated by RNA recognition motifs 3+4.
AB  - Vasopressin (VP) mRNA and the non-coding BC200 RNA are sorted to neuronal
      dendrites. Among proteins interacting specifically with both RNAs is the
      multifunctional poly(A)-binding protein (PABP) consisting of four RNA recognition
      motifs (RRMs) and a C-terminal auxiliary domain. The protein/RNA interaction
      studies presented here reveal that PABPs association with VP- and BC200 RNA is
      exclusively mediated by RRMs 3+4. Quantitative binding studies with PABP deletion
      mutants demonstrate preferential binding of RRMs 3+4 even to poly(A)
      homopolymers, while RRMs 1+2 exhibit a lower affinity for those sequences. An
      optimal interaction with both poly(A)- and non-poly(A) sequences is only achieved
      by full-size PABP.

PMID- 15498577
TI  - The iron-sulfur cluster in the L-serine dehydratase TdcG from Escherichia coli is
      required for enzyme activity.
AB  - The anaerobically inducible L-serine dehydratase, TdcG, from Escherichia coli was
      characterized. Based on UV-visible spectroscopy, iron and labile sulfide
      analyses, the homodimeric enzyme is proposed to have two oxygen-labile [4Fe-4S]2+
      clusters. Anaerobically isolated dimeric TdcG had a kcat of 544 s(-1) and an
      apparent KM for L-serine of 4.8 mM. L-threonine did not act as a substrate for
      the enzyme. Exposure of the active enzyme to air resulted in disappearance of the
      broad absorption band at 400-420 nm, indicating a loss of the [4Fe-4S]2+ cluster.
      A concomitant loss of dehydratase activity was demonstrated, indicating that
      integrity of the [4Fe-4S]2+ cluster is essential for enzyme activity.

PMID- 15498578
TI  - Calcium inhibits muscle FBPase and affects its intracellular localization in
      cardiomyocytes.
AB  - As our recent investigation revealed, in mammalian heart muscle, fructose 1,6
      bisphosphatase (FBPase)--a key enzyme of glyconeogenesis--is located around the Z
      line, inside cells' nuclei and, as we demonstrate here for the first time, it
      associates with intercalated discs. Since the degree of association of numerous
      enzymes with subcellular structures depends on the metabolic state of the cell,
      we studied the effect of elevated Ca2+ concentration on localization of FBPase in
      cardiomyocytes. In such conditions, FBPase dissociated from the Z-line, but no
      visible effect on FBPase associated with intercalated discs or on the nuclear
      localization of the enzyme was observed. Additionally, Ca2+ appeared to be a
      strong inhibitor of muscle FBPase.

PMID- 15498580
TI  - A GFP fluorescence-based approach to determine detergent insolubility of the
      human serotonin1A receptor.
AB  - Insolubility in non-ionic detergents such as Triton X-100 is a widely used
      biochemical criterion for characterization of membrane domains. We report here a
      novel green fluorescent protein fluorescence-based approach to directly determine
      detergent insolubility of specific membrane proteins. We have applied this method
      to explore the detergent resistance of an important G-protein coupled receptor,
      the serotonin1A (5-HT1A) receptor. Our results show, for the first time, that a
      small yet significant fraction of the 5-HT1A receptor exhibits detergent
      insolubility. These results are validated by control experiments involving
      fluorescent lipid probes and protein markers. Our results assume relevance in the
      context of localization of the 5-HT1A receptor in membrane domains and its
      significance in receptor function and signaling.

PMID- 15498579
TI  - Redox-dependent modulation of the carrot SV channel by cytosolic pH.
AB  - Currents mediated by a slow vacuolar (SV) channel were recorded and characterized
      in vacuoles from cultured carrot cells. The carrot channel shows the typical
      functional characteristics reported for channels of the SV category previously
      identified in other plants, i.e., slow voltage-dependent activation kinetics,
      current activation favoured by cytosolic calcium and permeability to different
      monovalent cations. The carrot channel is strongly activated by cytosolic
      reducing agents (such as dithiothreitol, DTT, and glutathione, GSH) and has a
      peculiar dependence on cytosolic pH, which, in turn, is affected by the
      concentration of cytosolic reducing agents. Specifically, in 1 mM DTT or GSH the
      channel displayed a maximum conductance at neutral pH. The normalized conductance
      did not depend significantly on DTT concentration at acidic pH, while at alkaline
      pH the attenuation of the normalized conductance declines with increasing DTT
      concentration. Our results suggest two pH-titratable groups within the carrot SV
      channel, one of these depending on cysteine residues exposed to the cytosolic
      side of the vacuole.

PMID- 15498581
TI  - Role of the fourth intracellular loop of D1-like dopaminergic receptors in
      conferring subtype-specific signaling properties.
AB  - We investigate whether the fourth intracellular loop (IL4) of D1 and D5
      dopaminergic receptors (D1R, D5R) confers D1-like subtype-specific signaling
      properties. Using chimeric receptors (D1R-IL4B and D5R-IL4A), we show that
      swapping of IL4 leads to a switch in dopamine affinity and constitutive activity
      of D1R and D5R. Dopamine potency was reduced for both chimeras in comparison with
      wild-type receptors. Moreover, dopamine-mediated maximal activation was
      drastically increased in cells expressing D1R-IL4B when compared with those
      harboring D5R-IL4A or wild-type receptors. In conclusion, IL4 plays a pivotal
      role in imparting subtype-specific ligand binding and activation properties to
      highly homologous seven-transmembrane receptors.

PMID- 15498582
TI  - A flexible approach for understanding protein stability.
AB  - A distance constraint model (DCM) is presented that identifies flexible regions
      within protein structure consistent with specified thermodynamic condition. The
      DCM is based on a rigorous free energy decomposition scheme representing
      structure as fluctuating constraint topologies. Entropy non-additivity is
      problematic for naive decompositions, limiting the success of heat capacity
      predictions. The DCM resolves non-additivity by summing over independent entropic
      components determined by an efficient network-rigidity algorithm. A minimal 3
      parameter DCM is demonstrated to accurately reproduce experimental heat capacity
      curves. Free energy landscapes and quantitative stability-flexibility
      relationships are obtained in terms of global flexibility. Several connections to
      experiment are made.

PMID- 15498583
TI  - Expression proteomics identifies biochemical adaptations and defense responses in
      transgenic plants with perturbed polyamine metabolism.
AB  - Soluble proteins from leaves of transgenic tobacco plants with perturbed
      polyamine metabolism, caused by S-adenosylmethionine decarboxylase
      overexpression, were analysed by comparative proteomics. A group of proteins was
      found to be increasingly repressed, in parallel with the degree of polyamine
      perturbation, in each of the three independent transgenic lines. These were
      identified as isoforms of chloroplast ribonucleoproteins, known to be involved in
      chloroplast mRNA stability, processing and translation. Another group of eight
      proteins strongly induced in the most metabolically perturbed line was identified
      as multiple, uncharacterised isoforms of the defense protein PR-1, a known marker
      for systemic acquired resistance.

PMID- 15498584
TI  - Small antisense RNA to cyclin D1 generated by pre-tRNA splicing inhibits growth
      of human hepatoma cells.
AB  - Introns are present in some human pre-tRNAs. They are spliced out during the
      maturation processes of pre-tRNAs in a way that is irrelevant to their specific
      nucleotide sequences. This unique characteristic of tRNA splicing can be used for
      generation of small antisense RNAs by replacing the intron sequences with
      corresponding antisense sequences. In this work, the intron sequence of human pre
      tRNAtyr gene was replaced with a 20 bp antisense sequence targeted to the 5'
      coding region of cyclin D1, a molecule that was over-expressed in many malignant
      proliferating cells. Under the control of U6 SnRNA promoter to further enhance
      transcription efficiency of the modified pre-tRNAtyr gene and subsequent
      antisense generation, the antisense RNA exhibited obvious suppression of cyclin
      D1 expression in H22 hepatoma cells. The growth of H22-transplanted tumors in
      mice was significantly inhibited when treated with naked plasmid DNA harboring
      the cyclin D1 antisense RNA generating cassette. Such tumor growth inhibition
      might be due to apoptosis caused by reduced cyclin D1 expression as revealed by
      immunohistochemical analysis of tumor samples.

PMID- 15498585
TI  - ETS-1 transcription factor activates the expression of mouse UDP
      Gal:GA2/GM2/GD2/GT2 galactosyltransferase gene.
AB  - UDP-Gal:GA2/GM2/GD2/GT2 galactosyltransferase (Gal-T2) transfers galactose to the
      terminal N-acetylgalactosamine of either the neutral glycolipid GA2 or of the
      gangliosides GM2, GD2 and GT2. Previous studies revealed a tight regulation of
      Gal-T2 activity and mRNA expression during development of the rat CNS. Here, we
      study in PC12 cells the cis-acting elements involved in the activation of a
      fragment of 211 bp around the transcription initiation site of the mouse Gal-T2
      promoter. Mutagenesis, competition experiments and functional assays showed that
      the Ets-1 transcription factor is involved in the activation of the Gal-T2
      promoter.

PMID- 15498586
TI  - An angiotensin II AT1 receptor antagonist, telmisartan augments glucose uptake
      and GLUT4 protein expression in 3T3-L1 adipocytes.
AB  - Evidence has accumulated that some of the angiotensin II AT1 receptor antagonists
      have insulin-sensitizing property. We thus examined the effect of telmisartan on
      insulin action using 3T3-L1 adipocytes. With standard differentiation inducers, a
      higher dose of telmisartan effectively facilitated differentiation of 3T3-L1
      preadipocytes. Treatment of both differentiating adipocytes and fully
      differentiated adipocytes with telmisartan caused a dose-dependent increase in
      mRNA levels for PPARgamma target genes such as aP2 and adiponectin. By contrast,
      telmisartan attenuated 11beta-hydroxysteroid dehydrogenase type 1 mRNA level in
      differentiated adipocytes. Of note, we demonstrated for the first time that
      telmisartan augmented GLUT4 protein expression and 2-deoxy glucose uptake both in
      basal and insulin-stimulated state of adipocytes, which may contribute, at least
      partly, to its insulin-sensitizing ability.

PMID- 15498587
TI  - If animals know their own fighting ability, the evolutionarily stable level of
      fighting is reduced.
AB  - We consider a version of the Hawk-Dove game in which an animal knows its own
      fighting ability but not the ability of its opponent. For this game at
      evolutionary stability there is a critical level of ability such that animals
      with ability greater than the critical level play Hawk and animals with ability
      below the critical level play Dove. We define the level of fighting to be the
      probability of a Hawk-Hawk fight when two opponents meet. We show that even if an
      animal does not know the ability of its opponent, knowing its own ability results
      in a lower level of fighting at evolutionary stability than is found in the
      standard Hawk-Dove game in which there are no differences in ability or abilities
      are not known.

PMID- 15498588
TI  - SLLE for predicting membrane protein types.
AB  - Introduction of the concept of pseudo amino acid composition (PROTEINS:
      Structure, Function, and Genetics 43 (2001) 246; Erratum: ibid. 44 (2001) 60) has
      made it possible to incorporate a considerable amount of sequence-order effects
      by representing a protein sample in terms of a set of discrete numbers, and hence
      can significantly enhance the prediction quality of membrane protein type. As a
      continuous effort along such a line, the Supervised Locally Linear Embedding
      (SLLE) technique for nonlinear dimensionality reduction is introduced (Science 22
      (2000) 2323). The advantage of using SLLE is that it can reduce the operational
      space by extracting the essential features from the high-dimensional pseudo amino
      acid composition space, and that the cluster-tolerant capacity can be increased
      accordingly. As a consequence by combining these two approaches, high success
      rates have been observed during the tests of self-consistency, jackknife and
      independent data set, respectively, by using the simplest nearest neighbour
      classifier. The current approach represents a new strategy to deal with the
      problems of protein attribute prediction, and hence may become a useful vehicle
      in the area of bioinformatics and proteomics.

PMID- 15498589
TI  - Virus evolution within patients increases pathogenicity.
AB  - Viruses like the human immunodeficiency virus (HIV), the hepatitis B virus (HBV),
      the hepatitis C virus (HCV) and many others undergo numerous rounds of inaccurate
      reproduction within an infected host. The resulting viral quasispecies is
      heterogeneous and sensitive to any selection pressure. Here we extend earlier
      work by showing that for a wide class of models describing the interaction
      between the virus population and the immune system, virus evolution has a well
      defined direction toward increased pathogenicity. In particular, we study virus
      induced impairment of the immune response and certain cross-reactive stimulation
      of specific immune responses. For eight different mathematical models, we show
      that virus evolution reduces the equilibrium abundance of uninfected cells and
      increases the rate at which uninfected cells are infected. Thus, in general,
      virus evolution makes things worse. An idea for combating HIV infection, however,
      is constructing a virus mutant that could outcompete the existing infection
      without being pathogenic itself.

PMID- 15498590
TI  - A model for the oscillatory motion of single dynein molecules.
AB  - Axonemal dynein is the molecular motor responsible for the rhythmic beating of
      eukaryotic cilia and flagella. An individual axonemal dynein molecule is capable
      of both unidirectional and oscillatory motion along a microtubule (Nature 393
      (1998) 711). We propose a model which links the physical motion of a two-headed
      dynein molecule to its ATP hydrolysis cycle, and which exhibits both processive
      and oscillatory behaviors. A mathematical analysis of the model is used to make
      experimentally testable predictions.

PMID- 15498591
TI  - A proposal for the physiological significance of mdr1 and Bcrp1/Abcg2 gene
      expression in normal tissue regeneration and after cancer therapy.
AB  - Cellular multi-drug resistance (MDR), which often develops in cancer cells of
      patients subjected to anti-cancer treatment, remains a significant barrier to
      successful cancer therapy. One of the principal causes of cellular MDR
      development is an increased expression of ABC-transporter genes such as mdr1 and
      Bcrp1/Abcg2. Despite many years of intensive research, the natural biological
      role of mdr1 in the context of cancer has remained elusive. Some hints about this
      role came, however, from an observation that P-gp, the mdr1 encoded protein, is
      expressed widely in stem cells and from the discovery that P-gp possesses an anti
      apoptotic activity independently of exogenous drug application. Here, we discuss
      our own and other groups' recently published works and propose an integrated view
      of mdr1 and Bcrp1/Abcg2 activity during tissue regeneration in normal tissues as
      part of a stress-induced regeneration genetic program and in cancerous tissues in
      response to cancer therapy.

PMID- 15498592
TI  - Equilibrium selection in evolutionary games with random matching of players.
AB  - We discuss stochastic dynamics of populations of individuals playing games. Our
      models possess two evolutionarily stable strategies: an efficient one, where a
      population is in a state with the maximal payoff (fitness) and a risk-dominant
      one, where players are averse to risks. We assume that individuals play with
      randomly chosen opponents (they do not play against average strategies as in the
      standard replicator dynamics). We show that the long-run behavior of a population
      depends on its size and the mutation level.

PMID- 15498593
TI  - DEMSIM: a discrete event based mechanistic simulation platform for gene
      expression and regulation dynamics.
AB  - In this paper, a discrete event based mechanistic simulation platform DEMSIM is
      developed for testing and validating putative regulatory interactions. The
      proposed framework models the main processes in gene expression, which are
      transcription, translation and decay processes, as stand-alone modules while
      superimposing the regulatory circuitry to obtain an accurate time evolution of
      the system. The stochasticity inherent to gene expression and regulation
      processes is captured using Monte Carlo based sampling. The proposed framework is
      applied to the extensively studied lac operon system, the SOS response system and
      the araBAD operon system of Escherichia coli. The results for the lac gene system
      demonstrate the simulation framework's ability to capture the dynamics of gene
      regulation, whereas the results for the SOS response system indicate that the
      framework is able to make accurate predictions about system behavior in response
      to perturbations. Finally, simulation studies for the araBAD system suggest that
      the developed framework is able to distinguish between different plausible
      regulatory mechanisms postulated to explain observed gene expression profiles.
      Overall, the obtained results highlight the effectiveness of DEMSIM at describing
      the underlying biological processes involved in gene regulation for querying
      alternative regulatory hypotheses.

PMID- 15498594
TI  - Network theory and SARS: predicting outbreak diversity.
AB  - Many infectious diseases spread through populations via the networks formed by
      physical contacts among individuals. The patterns of these contacts tend to be
      highly heterogeneous. Traditional "compartmental" modeling in epidemiology,
      however, assumes that population groups are fully mixed, that is, every
      individual has an equal chance of spreading the disease to every other.
      Applications of compartmental models to Severe Acute Respiratory Syndrome (SARS)
      resulted in estimates of the fundamental quantity called the basic reproductive
      number R0--the number of new cases of SARS resulting from a single initial case-
      above one, implying that, without public health intervention, most outbreaks
      should spark large-scale epidemics. Here we compare these predictions to the
      early epidemiology of SARS. We apply the methods of contact network epidemiology
      to illustrate that for a single value of R0, any two outbreaks, even in the same
      setting, may have very different epidemiological outcomes. We offer quantitative
      insight into the heterogeneity of SARS outbreaks worldwide, and illustrate the
      utility of this approach for assessing public health strategies.

PMID- 15498595
TI  - DNA in phosphorus atom representation: the heteronomous double helices of
      poly(dA).poly(dT) and poly(dG).poly(dC) and simulation of the yeast genome and of
      a human chromosome DNA.
AB  - We extracted phosphorus atom coordinates from the database of DNA crystal
      structures and calculated geometrical parameters needed to reproduce the crystal
      structures in the phosphorus atom representation. Using the geometrical
      parameters we wrote a piece of software assigning the phosphorus atom coordinates
      to the DNA of any nucleotide sequence. The software demonstrates non-negligible
      influence of the primary structure on DNA helicity, which may stand behind the
      heteromonous double helices of poly(dA).poly(dT) and poly(dG).poly(dC). In
      addition, the software is so simple that it makes possible to simulate the
      "crystal" structures of not only viral DNAs, but also the whole genome of
      Saccharomyces cerevisiae as well as the DNA human chromosome 22 having dozens of
      megabases in length.

PMID- 15498596
TI  - Calculation of binding length of base-specific DNA dyes by comparison of sequence
      and flow cytometric data. Application to Oryza sativa and Arabidopsis thaliana.
AB  - From biochemical experiments it has been found that AT- and GC-specific dyes need
      a certain number of consecutive bases of the same type for binding one dye
      molecule. From known base sequences the amount of bases included in dye binding
      can be calculated and compared with experimental data from flow cytometry. Oryza
      sativa and Arabidopsis thaliana are the first higher plants which are nearly
      completely (>90%) sequenced. From the published sequences the theoretical
      fluorescence intensity of base-specific dyes in relation to a base-unspecific dye
      is calculated for different binding lengths. These values are compared with the
      actual fluorescence intensities of nuclei analyzed by flow cytometry. For all
      investigated dyes (DAPI, Hoechst 33258, Hoechst 33342 (all AT specific) and
      Mithramycin A (GC specific)) a binding length of 1 bp results from the comparison
      of theoretical and experimental data. This is, however, in disagreement with
      former results on dye binding. The main reason for the discrepancy seems to be
      the remaining gap in the sequencing of the Arabidopsis genome.

PMID- 15498597
TI  - The iterated continuous prisoner's dilemma game cannot explain the evolution of
      interspecific mutualism in unstructured populations.
AB  - The evolutionionary origin of inter- and intra-specific cooperation among non
      related individuals has been a great challenge for biologists for decades.
      Recently, the continuous prisoner's dilemma game has been introduced to study
      this problem. In function of previous payoffs, individuals can change their
      cooperative investment iteratively in this model system. Killingback and Doebeli
      (Am. Nat. 160 (2002) 421-438) have shown analytically that intra-specific
      cooperation can emerge in this model system from originally non-cooperating
      individuals living in a non-structured population. However, it is also known from
      an earlier numerical work that inter-specific cooperation (mutualism) cannot
      evolve in a very similar model. The only difference here is that cooperation
      occurs among individuals of different species. Based on the model framework used
      by Killingback and Doebeli (2002), this Note proves analytically that mutualism
      indeed cannot emerge in this model system. Since numerical results have revealed
      that mutualism can evolve in this model system if individuals interact in a
      spatially structured manner, our work emphasizes indirectly the role of spatial
      structure of populations in the origin of mutualism.

PMID- 15498598
TI  - A potential role of modulating inositol 1,4,5-trisphosphate receptor
      desensitization and recovery rates in regulating ovulation.
AB  - Regulation of the human menstrual cycle is a frequency dependent process
      controlled in part by the pulsatile release of gonadotropin releasing hormone
      (GnRH) from the hypothalamus. The binding of GnRH to gonadotroph cells in the
      pituitary stimulates inositol 1,4,5-trisphosphate (IP3) mediated release of
      calcium from the endoplasmic reticulum, resulting in calcium oscillations and the
      secretion of luteinizing hormone (LH). A sudden increase in serum LH
      concentrations known as the LH surge triggers ovulation. Here we model the
      intracellular calcium dynamics of gonadotroph cells by adapting the model of Li
      and Rinzel (J. Theor. Biol. 166 (1994) 461) to include the desensitization of IP3
      receptors to IP3. Allowing the resensitization rate of these receptors to vary
      over the course of the cycle suffices to explain the LH surge in both the normal
      menstrual cycle, and in the treatment of Kallmann's syndrome (a condition where
      endogenous production of GnRH is absent).

PMID- 15498599
TI  - Range size in mid-domain models of species diversity.
AB  - Geographical patterns of species diversity have been examined using mid-domain
      null models, in which the ranges of individual species are simulated by randomly
      arranging them on a bounded one- or two-dimensional continent. These models have
      shown that structured patterns in the geographical distribution of biodiversity
      can arise even under a fully stochastic procedure. In particular, mid-domain
      models have demonstrated that the random generation of ranges of different sizes
      and locations can produce a gradient of species diversity similar to the one
      found in real assemblages, with a peak at the middle of a continent. A less
      explored feature of mid-domain models is the pattern of range-size frequency
      distribution. Numerical simulations have provided some insights about the
      geographic pattern of average range size, but no exploration of the shape of
      range-size frequency distributions has been carried out. Here I present
      analytical and numerical models that generate explicit predictions for patterns
      of range size under the assumptions of mid-domain models of species diversity.
      Some generalizations include: (1) Mid-domain models predict no geographic
      gradient of average range size; the mean range size of species occurring at any
      point on a continent is constant (0.5 of the extent of the continent in the one
      dimensional model, 0.25 of the area of the continent in the two-dimensional
      case); (2) Variance in range size is lowest at the middle of a continent and
      highest near the corners of a square-shaped continent; (3) The range-size
      frequency distribution is highly right-skewed at any point of a continent, but
      the skewness is highest near the corners. Despite their alleged weaknesses, mid
      domain models are adequate null models against which real-world patterns can be
      contrasted.

PMID- 15498600
TI  - Understanding foraging behaviour in spatially heterogeneous environments.
AB  - The role of stochasticity and spatial heterogeneity in foraging systems is
      investigated. We formulate a spatially explicit model which describes the
      behaviour of grazing animals in response to local information using simple
      stochastic rules. In particular the model reflects the biology in that decisions
      to move to a new location are based on visual assessment of the sward height in a
      surrounding neighbourhood, whilst the decision to graze the current location is
      based on the residual sward height and olfactory assessment of local faecal
      contamination. It is assumed that animals do not interact directly, but do so
      through modification of, and response to a common environment. Spatial
      heterogeneity is shown to have significant effects including reducing the
      equilibrium intake rate and increasing the optimal stocking density, and must
      therefore be taken into account by resource managers. We demonstrate the
      relationship between the stochastic spatial model and its non-spatial
      deterministic counterpart, and in the process derive a moment-closure
      approximation to the full process, which can be regarded as an intermediate, or
      pseudo-spatial model. The role of spatial heterogeneity is emphasized, and better
      understood by comparing the results obtained from each approach. The relative
      efficiency of random and directed searching behaviour in spatially heterogeneous
      environments is explored for both clean and contaminated pastures, and the impact
      of faecal avoidance behaviour assessed.

PMID- 15498601
TI  - Spatially correlated disturbances in a locally dispersing population model.
AB  - The basic contact process in continuous time is studied, where instead of single
      occupied sites becoming empty independently, larger-scale disturbance events
      simultaneously remove the population from contiguous blocks of sites. Stochastic
      spatial simulations and pair approximations were used to investigate the model.
      Increasing the spatial scale of disturbance events increases spatial clustering
      of the population and variability in growth rates within localized regions,
      reduces the effective overall population density, and increases the critical
      reproductive rate necessary for the population to persist. Pair approximations
      yield a closed-form analytic expression for equilibrium population density and
      the critical value necessary for persistence.

PMID- 15498602
TI  - Resiquimod: a new immune response modifier with potential as a vaccine adjuvant
      for Th1 immune responses.
AB  - Genital herpes is one of the most common sexually transmitted diseases worldwide.
      Currently, there are three FDA-approved nucleoside analogs and other therapies
      such as foscarnet and cidofovir used to treat genital herpes. Resiquimod, the
      latest immune response modifier (IRM), has shown in vivo evidence of efficacy
      against herpes simplex virus (HSV) type 2. The first clinical trial involving
      resiquimod demonstrated that it reduced the recurrence rate of genital herpes,
      but phase III trials were suspended due to lack of efficacy. Resiquimod shows
      promise for other viral infections and as a vaccine adjuvant.

PMID- 15498603
TI  - Evaluation of a Western Equine Encephalitis recombinant E1 protein for protective
      immunity and diagnostics.
AB  - The E1 and E2 glycoproteins of Western Equine Encephalitis (WEE) are candidate
      antigens for WEE subunit vaccine development. We have cloned the E1 gene of WEE
      virus and expressed it in Escherichia coli as inclusion bodies. The inclusion
      bodies were successfully solubilised, refolded and the immunogenicity of this
      unglycosylated protein was assessed in mice. Immunization of mice with
      recombinant E1 protein generated both humoral and cell-mediated immune responses,
      indicating the recombinant E1 protein is immunogenic. Challenge of E1-immunized
      mice with live WEE virus demonstrated little or no protection from this E. coli
      derived non-glycosylated subunit.

PMID- 15498604
TI  - Concerted inhibitory activities of Phyllanthus amarus on HIV replication in vitro
      and ex vivo.
AB  - Phyllanthus amarus derived preparations were previously shown to inhibit RT
      inhibitor-resistant HIV variants as efficiently as wild-type strains. The drugs
      target different steps of the HIV life cycle, thereby presenting multiple
      antiviral activities. Here we show that a water/alcohol extract blocks HIV-1
      attachment and the HIV-1 enzymes integrase, reverse transcriptase and protease to
      different degrees. A gallotannin containing fraction and the isolated
      ellagitannins geraniin and corilagin were shown to be the most potent mediators
      of these antiviral activities. The P. amarus derived preparations blocked the
      interaction of HIV-1 gp120 with its primary cellular receptor CD4 at 50%
      inhibitory concentrations of 2.65 (water/alcohol extract) to 0.48 microg/ml
      (geraniin). Inhibition was also evident for the HIV-1 enzymes integrase (0.48
      0.16 microg/ml), reverse transcriptase (8.17-2.53 microg/ml) and protease (21.80
      6.28 microg/ml). In order to prove the in vivo relevance of these biological
      activities, plant material was administered orally to volunteers and a potent
      anti-HIV activity in blood could be demonstrated. Sera at a final concentration
      of 5% reduced HIV replication by more than 30%. These results support the
      conclusion that P. amarus has inhibitory effects on HIV not only in vitro but
      also in vivo.

PMID- 15498606
TI  - Prevention and elimination of bovine viral diarrhea virus infections in fetal
      fibroblast cells.
AB  - Noncytopathic infections with bovine viral diarrhea virus (BVDV) can compromise
      research and commercial use of cultured cells. The purpose of this research was
      to evaluate the ability of aromatic cationic compounds to prevent or treat BVDV
      infections in fetal fibroblast cell lines that are used in somatic cell nuclear
      transfer. To evaluate preventative use of compounds, 10 cell lines were
      inoculated with BVDV in the absence or presence of 2-(4-[2-imidazolinyl]phenyl)-5
      (4-methoxyphenyl)furan (DB606), 2-(2-benzimidazolyl)-5-[4-(2
      imidazolino)phenyl]furan dihydrochloride (DB772), or 2-(1-methyl-2
      benzimidazolyl)-5-[4'-(2-imidazolino)-2'-methylphenyl]furan dihydrochloride
      (DB824). The 99% endpoints for prevention of viral replication by these
      treatments were 81, 6, and 14 nM. To evaluate therapeutic use of compounds, two
      fetal fibroblast cell lines infected with a genotype 1a strain of BVDV were
      cultured through four passages in the absence or presence of either 0.04 or 4
      microM concentrations of DB772 or DB824. The presence and concentration of BVDV
      in media and cell lysates were evaluated using reverse transcription nested
      polymerase chain reaction and virus isolation from titrated sample. A single
      passage in 4 microM of either compound was sufficient to eliminate BVDV from
      cells without causing cytotoxicity. Our results demonstrate that in vitro
      infections with BVDV can be effectively prevented or eliminated by addition of
      aromatic cations.

PMID- 15498605
TI  - A phase II, double-masked, randomized, placebo-controlled evaluation of a human
      monoclonal anti-Cytomegalovirus antibody (MSL-109) in combination with standard
      therapy versus standard therapy alone in the treatment of AIDS patients with
      Cytomegalovirus retinitis.
AB  - ACTG 266 was designed as a randomized study to evaluate two doses of the human
      monoclonal antibody directed against CMV gH (MSL-109) versus placebo, each in
      combination with standard antiviral therapy for the treatment of newly diagnosed
      Cytomegalovirus (CMV) retinitis in AIDS patients. A total of 82 subjects were
      enrolled and received either placebo (n = 28), or MSL-109 at 15 mg (n = 26) or 60
      mg (n = 28) every 2 weeks until disease progression was diagnosed. The primary
      endpoint, disease progression, was determined by masked reading of retinal
      photographs taken every 4 weeks read by a single investigator. The median time to
      progression was 8.0, 8.3, and 12.1 weeks in the placebo, MSL-109 15mg and MSL-109
      60 mg cohorts, respectively (P = 0.087, placebo versus 60 mg cohort). There were
      22 deaths during the study period (9, 9, and 4 in the placebo, MSL-109 15 mg and
      MSL-109 60 mg cohorts, respectively (P = 0.0058, placebo versus 60 mg cohort)).
      MSL-109 was well tolerated with no significant adverse events attributable to
      study medication. The unexplained survival advantage in the higher dose cohort
      was discordant with the findings of the parallel Studies of Ocular Complications
      of AIDS Research Group (SOCA)-Monoclonal Anti-CMV Retinitis Trial (MACRT), which
      was prematurely halted because of increased mortality in subjects treated with
      high-dose MSL-109, recognizing that A266 enrolled subjects with newly diagnosed,
      whereas the MACRT enrolled subjects with relapsed, CMV retinitis.

PMID- 15498607
TI  - A wide range of medium-sized, highly cationic, alpha-helical peptides show
      antiviral activity against herpes simplex virus.
AB  - Ten highly cationic, alpha-helical peptides were synthesized and tested for
      antiviral activity against herpes simplex virus 1 and 2 (HSV-1 and HSV-2).
      Several of the peptides were found to exhibit antiviral activity. The peptides
      affinity for heparan sulfate (HS) increased with the number of cationic residues.
      Net charge could be decisive for the anti-HSV-1 activity, while secondary
      structure of the peptides seems more important for the anti-HSV-2 activity. The
      peptides were able to inhibit the entry of HSV-1 into the host cell, probably by
      blocking HS at the cell surface. HSV plaque formation was inhibited in a dose
      dependent manner when cells were exposed to the peptides prior to the addition of
      virus. Lower inhibition activity was observed when the virus was allowed to
      attach to the cell surface before the addition of peptide. However, the plaque
      size was smaller compared to the untreated control, indicating that the peptides
      may also interfere with cell-to-cell spread of the virus. The two most potent
      antiviral peptides exhibited synergy with acyclovir against HSV.

PMID- 15498608
TI  - The synergistic effects of betulin with acyclovir against herpes simplex viruses.
AB  - Betulin, a pentacyclic triterpenoid, was isolated from the bark of Betula
      papyrifera. The antiviral efficacies of betulin on herpes simplex virus type 1
      (HSV-1) and type 2 (HSV-2) were evaluated using viral plaque reduction assays on
      Vero cells. The results indicate that betulin is active against both HSV-1 and
      HSV-2 infections with the 50% effective concentrations (EC(50)) of 0.40 and 4.15
      microg/ml, respectively. The cytotoxicity of betulin was examined on Vero cells
      using a neutral red uptake assay. The 50% cytotoxic concentration (CC(50)) of
      betulin was 73.1 microg/ml. A synergistic antiviral effect between betulin and
      acyclovir (ACV) was determined by drug combination studies. Strong and moderate
      synergistic antiviral effects were observed for betulin and ACV against HSV-1
      when the concentrations of ACV and betulin were higher than 0.068 and 0.4
      microg/ml, respectively. At the concentrations lower than these, additive effect
      was found. Synergistic antiviral effects were also found against HSV-2 at higher
      concentrations than for HSV-1, i.e. 0.45 microg/ml of ACV combined with 8.4
      microg/ml of betulin.

PMID- 15498609
TI  - Co-expression of interleukin-2 to increase the efficacy of DNA vaccine-mediated
      protection in coxsackievirus B3-infected mice.
AB  - DNA immunizations with the major structural protein VP1 of coxsackievirus B3
      (CVB3) have been previously found to protect mice from a lethal challenge with
      CVB3. The function of this vaccination procedure is mainly based on accelerated
      antibody induction with an early cytokine expression and increased virus-specific
      cytotoxic activity of spleen cells causing decreased myocyte destruction and
      reduced viral replication. Here, we report that the co-expression of the immune
      stimulatory interleukin-2 (IL-2) can increase the efficacy of the inoculated DNA
      vaccine depending on the route of administration and the mouse strain used.

PMID- 15498611
TI  - Certified mail fails to reach an Emergency Department population.
AB  - The objective of this study was to determine if correspondence sent by regular
      mail would be delivered more often than correspondence sent by certified mail.
      Correspondence was prospectively randomized and mailed by United States Postal
      Service using either regular mail service or certified mail service. Mailings
      were analyzed based on patient demographic information, whether or not mail was
      returned, and the reason for the return. Certified mail was sent to 145 patients;
      58 (40%) of the mailings were returned. Wrong addresses accounted for only 23
      (16%) of these, whereas the addressee never claimed 35 (24%). Regular mail was
      sent to 126 patients, and 19 (15%) of the letters were returned. Wrong addresses
      accounted for 18 (14%) of these letters, and only 1 (1%) was refused for
      delivery. In conclusion, when compared with certified mail, regular mail is a
      more effective means of reaching patients with follow-up information after an
      Emergency Department visit.

PMID- 15498610
TI  - Protective effect of a natural carrageenan on genital herpes simplex virus
      infection in mice.
AB  - In the present study, the protective effect of 1T1, a lambda-carrageenan
      extracted from the red seaweed Gigartina skottsbergii was evaluated in a murine
      model of herpes simplex virus type 2 (HSV-2) genital infection. Six to eight-week
      old female BALB/c mice were intravaginally inoculated with a lethal dose of HSV-2
      (MS strain) and pre- or post-infection treated with different doses of a 10mg/ml
      solution of 1T1. A single topical administration of 1T1 shortly before infection
      of BALB/c mice with HSV-2 protected 9 out of 10 mice from HSV-2-induced lesions
      and mortality, compared with only 10% survival in control mice. In addition, 1T1
      produced a total blockade in virus shedding in the vaginal secretions. When 1T1
      pre-treatment was reinforced with a second dose 2h after infection, total
      protection was observed even when the prophylactic administration had taken place
      at 60min before infection. The irreversible virucidal action of 1T1 against
      herpes virus seems to be responsible of its protective effect against virus
      replication and mortality following vaginal HSV-2 infection.

PMID- 15498612
TI  - Population characteristics of traffic accident-related deaths in Japan and
      Ireland, 1950-2000.
AB  - To compare epidemiological characteristics of traffic accidents in Japan and
      Ireland, we analyzed mortality and the negative effect on life expectancy between
      1950 and 2000 and generated a multivariate model. The characteristics were
      similar in the two countries: The time trends showed an increase in mortality
      followed by a decrease. The mortality rates were about 13 and 5/100,000 for males
      and females, respectively, in 2000. Correlation coefficients for sex were over
      0.9. Age distribution obeyed the natural logarithm regularity. The negative
      effect on life expectancy was about 0.34 year for males, and 0.13 year for
      females. The economic level was positively associated with mortality, whereas
      "number of vehicles owned" was associated negatively. In conclusion, we can take
      advantage of the broad consistencies in these two countries when we draw up an
      intervention strategy. Any preventive strategy should be directed to the young,
      particularly males.

PMID- 15498613
TI  - Do patients with a negative Emergency Department evaluation for syncope require
      hospital admission?
AB  - Is hospitalization needed for patients in whom an underlying cause of syncope is
      not detected in the Emergency Department (ED)? To answer this question, we
      conducted a prospective, short-term outcomes study of consecutive patients > or =
      50 years old presenting to our ED after a syncopal episode. All subjects received
      a structured ED evaluation. Forty-five patients met inclusion criteria, 67% were
      hospitalized. None of the patients experienced a life-threatening event or
      required significant therapeutic interventions during the hospitalization. No
      patient had a new diagnosis relevant to syncope. Follow-up interviews 1 month
      later revealed no repeat ED visits, hospitalizations, or deaths (95% upper CI,
      6.5%). One patient reported a recurrent syncope (recurrence 2.2% [95% upper CI,
      10%]). This pilot study suggests that a negative structured ED evaluation may
      identify patients > or = 50 years of age who may be safely discharged from the
      ED. Further validation is required before this observation is applied to clinical
      practice.

PMID- 15498614
TI  - Potential diversion rates associated with prehospital acute myocardial infarction
      triage strategies.
AB  - Thisstudy examines the potential number of patients who would be diverted from
      hospitals without percutaneous coronary intervention (PCI) capability, to centers
      with this capability, as a result of prehospital triage strategies for patients
      with suspected acute myocardial infarction (AMI). All patients with AMI admitted
      during a 1-year study period at two urban hospitals without PCI capability were
      identified through a prospectively maintained AMI registry. Pertinent clinical
      data were extracted from the AMI registry and patients' medical records. Patients
      were considered to have been eligible for prehospital diversion to a PCI center
      if they had ischemic symptoms of greater than 20 min and less than 24 h duration,
      and electrocardiographic changes consistent with ST elevation AMI (STEMI) were
      noted at the time of Emergency Department (ED) arrival or before arrival. There
      were 176 patients with AMI identified. One hundred three patients were
      transported to the ED by Emergency Medical Services (EMS). Of these, 39 had a
      clinical presentation and diagnostic EKG evidence of STEMI on ED arrival.
      Implementation of a prehospital triage strategy for patients with suspected STEMI
      may result in the diversion of 22% of patients with AMI from hospitals without
      PCI capability, assuming perfect specificity of prehospital triage. Actual
      implementation of a prehospital AMI diversion protocol may have an even greater
      impact on nonreceiving hospitals.

PMID- 15498615
TI  - A rare case of concomitant viral myocarditis and pericarditis in a 44-year-old
      patient.
AB  - Concomitant severe myocarditis and pericarditis are under-recognized or rare. We
      report a case of a 44-year-old woman who presented in shock after a week of a flu
      like illness and several hours of severe back pain. Emergent echocardiography
      revealed cardiac tamponade for which pericardiocentesis achieved transient
      improvement. Unfortunately, the patient died 2 days later secondary to
      progressive cardiomyopathy and multi-system organ failure. Post-mortem studies of
      the heart were consistent with coxsackie virus myocarditis. Diagnosis and
      treatment of myocarditis and pericarditis are discussed, including clues to
      detecting concurrent disease processes.

PMID- 15498616
TI  - Post-traumatic subdural hygroma: case report.
AB  - Subdural Hygroma (SDG) is described in the literature as a common complication of
      blunt head trauma occurring in a reported 5-20% of all closed head injuries. The
      Emergency Physician will likely encounter this type of lesion and it is useful to
      have an understanding of its significance, its relationship to subdural hematoma
      (SDH), and management strategies. Although surgical intervention is often
      advocated in the treatment of intracranial fluid collections causing mass effect,
      there are several reported cases of spontaneous resolution of uncal and central
      herniation via conservative management alone. The authors report a case of a 90
      year-old woman who presented to the Emergency Department 5 days after falling and
      sustaining a closed head injury with computed tomography (CT) scan evidence of
      mid-line shift.

PMID- 15498617
TI  - Aniline and methanol toxicity after shoe dye ingestion.
AB  - A 39-year-old woman intentionally ingested Amberes shoe dye containing both
      methanol and aniline. She subsequently developed life-threatening methanol
      poisoning, methemoglobinemia, hemolytic anemia, and sulfhemoglobinemia. Treatment
      involved methylene blue infusion, emergent hemodialysis, fomepizole therapy, and
      blood products. Multiple toxicities can occur after ingestion of shoe dyes.

PMID- 15498618
TI  - Anaphylaxis in the prehospital setting.
AB  - Many Emergency Medical Services (EMS) systems have adopted epinephrine auto
      injector (EAI) use by Basic Life Support (BLS) personnel, and several states now
      require that BLS personnel be trained and authorized to use EAIs. The objectives
      of this observational study were: 1) to examine EMS case definitions of
      allergy/anaphylaxis, 2) to ascertain the incidence of EMS calls for
      allergy/anaphylaxis and administration of epinephrine, and 3) to quantify the
      rate of deaths due to anaphylaxis. Data were solicited by e-mail, mail, and
      telephone from National Association of State EMS Directors (NASEMSD) members,
      state EMS offices, and state medical examiner and vital statistics offices.
      Simple descriptive statistics were used to analyze the data. The following was
      found: 1) there is no standardization of case definitions among states. Some use
      the terms "allergic reaction" and "anaphylaxis" in EMS protocols without
      definition, whereas others provide lengthy, specific definitions, with detailed
      criteria for epinephrine administration; 2) excluding two outliers at 0.04% and
      3.9%, nine EMS system databases totaling over 2.8 million runs contained between
      0.34% and 0.82% of runs for allergy/anaphylaxis. Seven of these databases
      reported on epinephrine administration, with rates between 0.16% and 31.1%, and
      four of the seven clustered between 8.8% and 14.8%. There was little uniformity
      in the data provided by seven states on deaths due to anaphylaxis, with rates
      from 0% to 0.94%. Although limited by the lack of data from many states, roughly
      0.5% of EMS runs are for allergy/anaphylaxis complaints, with epinephrine
      administered in roughly one-tenth of these. State death rates from anaphylaxis
      vary considerably, with rates from 0% to 0.94% reported.

PMID- 15498621
TI  - Electrocardiographic manifestations: long QT Syndrome.
AB  - Long QT Syndrome is a cardiac disorder caused by an abnormal prolongation of the
      ventricular repolarization phase. The primary concern in this syndrome is the
      propensity towards polymorphic ventricular tachycardia and sudden cardiac death.
      This article presents several cases, highlighting the pathophysiology, clinical
      presentation, and management of this disorder.

PMID- 15498620
TI  - Difficult airways: the aspirated dreidel.

PMID- 15498622
TI  - Safety and efficacy of sequential i.v. to p.o. moxifloxacin versus conventional
      combination therapies for the treatment of community-acquired pneumonia in
      patients requiring initial i.v. therapy.
AB  - To compare the efficacy of sequential i.v. to p.o. moxifloxacin with ceftriaxone
      +/- azithromycin +/- metronidazole for the treatment of patients with community
      acquired pneumonia (CAP), a multi-centered, prospective, randomized, open label
      study was performed. CAP patients were randomized to moxifloxacin (400 mg/d-at
      least one i.v. dose) or ceftriaxone (at least one dose of 2 g i.v. q.d. followed
      by cefuroxime 500 mg p.o. b.i.d.) +/- azithromycin, +/- metronidazole
      (cephalosporin/macrolide control: CMC). The primary endpoint was clinical
      response at test-of-cure (TOC) visit. Bacteriological response at TOC was the
      secondary endpoint. Clinical cure was found in 83.3% (90/108) of moxifloxacin
      patients and 79.6% (90/113) of control patients. Microbiological responses were
      81.8% (18/22) for moxifloxacin and 60.7% (17/28) for CMC patients. Drug-related
      adverse events occurred in 18.0% of moxifloxacin and 16% of CMC patients. It is
      concluded that i.v. to p.o. moxifloxacin is as effective as CMC for treatment of
      CAP and is a reliable alternative antimicrobial therapy.

PMID- 15498623
TI  - Fever.

PMID- 15498624
TI  - Extraperitoneal bladder rupture and posterior urethral injury.

PMID- 15498625
TI  - Rocky Mountain Spotted Fever, another important cause of fever and rash.

PMID- 15498626
TI  - Regarding the case presentation of the Harvard Emergency Medicine residency,
      "fever and rash".

PMID- 15498627
TI  - Termination of idiopathic persistent singultus (hiccup) with supra-supramaximal
      inspiration.

PMID- 15498629
TI  - Stress testing in patients with cocaine-associated chest pain.

PMID- 15498630
TI  - Physician and nurse satisfaction with an Electronic Medical Record system.
AB  - Electronic Medical Records (EMRs) are intended to support clinical activity,
      improve efficiency, and reduce error. Reluctance to use EMRs may exist among
      clinicians. The purpose of this study was to assess physician and nurse
      satisfaction with an Emergency Department (ED) EMR. We surveyed Emergency
      Medicine (EM) physicians and nurses at a large urban teaching hospital after
      implementation of an Emergency Department EMR. The questionnaire assessed: 1)
      computer background and experience; 2) perceptions regarding EMR use; and 3)
      concerns about impact upon quality of patient care. The clinicians find the EMR
      easy to use and are generally satisfied with the impact on their work. However,
      they report that the EMR has no positive impact on patient care. They report
      confusion in following the sequence of screens, and are concerned with the amount
      of time it takes to use the EMR and the confidentiality of patient information.
      Similar results were found between physicians and nurses. Nurses, but not
      physicians, report that they are able to finish work much faster than before
      implementation (p < 0.05). We were unable to correlate computer background and
      experience with satisfaction with an EMR. This survey suggests that EM physicians
      and nurses favor the use of an EMR and suggests opportunities for EMR
      enhancement.

PMID- 15498631
TI  - Loss/gain.

PMID- 15498632
TI  - Adjuvant therapy following surgery for periampullary and pancreatic cancers.

PMID- 15498634
TI  - Radioguided occult lesion localisation (ROLL) and sentinel node biopsy for
      impalpable invasive breast cancer.
AB  - AIM: The aim of this study was to simplify the technique of ROLL and sentinel
      node biopsy without compromising tumour excision and sentinel node biopsy.
      METHODS: Twenty patients with impalpable primary invasive breast carcinoma
      underwent an injection of 99mTc-nanocolloid mixed with radiographic contrast
      medium Iohexol into the centre of the lesion under ultrasound or stereotactic
      guidance pre-operatively. No guidewire localisation was performed. Under general
      anaesthesia, a periareolar intradermal/subcutaneous injection of patent blue-V
      dye was performed. The sentinel node was identified by blue-stained lymphatics
      and node and a hot spot on the gamma probe. Surgical excision of the primary
      tumour was then carried out using the gamma probe. RESULTS: In eight of 20 cases
      an immediate re-excision was carried out and on histological assessment, all 20
      patients were clear of invasive disease at the margins. In two patients, in situ
      disease was present at the margins and a further re-excision was therefore
      performed. The sentinel node was identified in all cases. In all, five of 20
      patients were node positive on routine HE staining. In a further two patients,
      tumour cells were identified by immunohistochemistry with CAM5.2 antibody.
      Completion axillary clearance in six patients confirmed that the sentinel node
      was the only positive node. CONCLUSIONS: This modification of the previously
      described ROLL technique is feasible and safe and does not compromise tumour
      excision or sentinel node detection.

PMID- 15498633
TI  - Blue dye versus combined blue dye-radioactive tracer technique in detection of
      sentinel lymph node in breast cancer.
AB  - BACKGROUND: Sentinel lymph node biopsy in breast cancer can be used to select
      patients in which axillary lymph node dissection could be avoided. In this study
      we compared the value of two methods for identification of sentinel node (SN)
      using either only blue dye or combination of blue dye and radioactive tracer.
      MATERIAL AND METHODS: All patients were women with clinically T(1-2)N(0)M(0)
      breast cancer. They were randomized into two groups. In Group A (50 patients) SN
      marking was performed only with blue dye and in Group B (100 patients) combined
      SN marking with blue dye and radiotracer was done. We used 2 ml of blue dye
      Patentblau V (Byk Gulden). Radiotracer was Antimony sulfide marked with Tc 99m
      and of 0.3 mCy (11.1 MBq) activity. Application method of both contrasts was
      peritumoral. After SN biopsy all patients underwent mastectomy or conservative
      surgery with axillary lymph node dissection of levels I and II. RESULTS: In Group
      A mean of 1.7 SNs were identified (median 1, range 1-4). False-negative rate in
      this group was 3/17 (17.6%) with negative-predictive value 20/23 (86.9%),
      sensitivity 14/17 (82%), specificity 20/33 (60%) and accuracy 34/50 (68%). In
      Group B mean number of SNs excised per case was 1.6 (median 1, range 1-5). False
      negative rate was 2/44 (4.5%), negative-predictive value 41/43 (95.3%),
      sensitivity 42/44 (95%), specificity 41/56 (73%) and accuracy 83/100 (83%). The
      combination technique was significantly superior to blue-dye alone technique for
      negative-predictive value (p=0.033) and overall accuracy (p=0.048). CONCLUSIONS:
      The prediction of axillary lymph node status in breast cancer patients using
      combined technique has significantly higher accuracy than marking of SN with blue
      dye alone and therefore should be preferred.

PMID- 15498636
TI  - Factors influencing outcome in gastric cancer involving muscularis and subserosal
      layer.
AB  - AIMS: The prognostic factors for advanced gastric carcinoma without serosal
      invasion (pT2 AGC) are not clear. In terms of prognosis, pT2 AGC is considered
      intermediate between early gastric cancer (EGC) and gastric carcinoma with
      serosal invasion. METHODS: From January 1985 to December 2000, 182 patients with
      pT2 AGC underwent curative gastric resection in our Department. Prognostic
      factors were evaluated by univariate and multivariate analyses. RESULTS:
      Univariate analysis demonstrated that gender, tumour location, lymph node
      involvement, Borrmann type, number of lymph nodes involved, venous infiltration
      and extent of lymphadenectomy were significantly related to the prognosis.
      Multivariate analysis revealed that extent of lymph node metastasis (N1 vs N0
      relative risk (RR) of recurrences=3.96, p<0.05; N2 vs N0 RR=6.55, p<0.05), and
      extent of lymphadenectomy (D1 vs D2 RR=3.2, p<0.01) were independent prognostic
      factors. In a subset of patients in which venous infiltration was analysed, this
      factor was also significant (RR=3.9, p<0.05). CONCLUSIONS: Our study shows that
      lymph node involvement and venous infiltration are important prognostic factors
      for pT2 AGC and, as such, adjuvant chemotherapy could be useful in this group of
      patients. An extensive lymph node dissection, minimum D2, should always be
      performed in order to reduce the risk of recurrence.

PMID- 15498635
TI  - Surgical implications of sentinel node with micrometastatic disease in invasive
      breast cancer.
AB  - AIM: To assess the rate of positive axillary clearance (AC) when the sentinel
      node biopsy (SNB) contains micrometastatic disease in invasive breast cancer and
      to evaluate the factors that could predict positivity. PATIENTS AND METHODS: This
      is a prospective study carried out on 542 successive women undergoing SNB for
      unifocal T0-T1 N0 invasive breast cancer without previous treatment. RESULTS:
      Five hundred and twenty-five sentinel nodes (SN) were found, 142 contained
      metastases. Fifty-five of the positive SN contained micrometastatic disease only.
      Of them, 40 patients underwent completion of AC. Six out of 40 patients who had
      micrometastatic SN had a positive AC, five for micrometastasis between 0.2 and 2
      mm (5/34), one for isolated cells in the SN (1/6). None of the studied factors
      (age, histological tumour size, histological grade, estradiol receptor (ER),
      histological tumour type, size and method of micrometastasis detection) could
      significantly predict the status of the AC. CONCLUSION: As long as the results of
      ongoing prospective randomised studies are unknown, it remains necessary to
      perform AC when the SNB contains micrometastatic disease, whatever the size or
      the detection mode of the metastasis.

PMID- 15498637
TI  - Determination of nodal status and treatment in early gastric cancer.
AB  - BACKGROUND: In view of its low associated risk of metastatic spread, early
      gastric cancer has an excellent prognosis. The basis for the choice of treatment
      is the risk of lymphogenous metastatic spread together with the individual
      surgical risk. METHODS: The data collected from 279 patients in whom, between
      01/1982 and 12/2001, a gastric resection or gastrectomy was carried out for early
      gastric cancer at the Surgical Department of the University Hospital, Erlangen,
      were analysed. A number of macroscopic and histopathological factors were
      examined by univariate and multivariate analysis for their effect on lymphogenous
      metastatic spread. RESULTS: In 33 patients (11.8%), regional lymph-node
      metastases were confirmed histologically. The grade of malignancy (high-grade,
      relative risk 9.9), diameter (>20 mm, relative risk 5.0) and lymphatic invasion
      (relative risk 3.5) all demonstrated a significant independent influence on the
      occurrence of regional lymph-node metastases. Seventy-three patients were
      identified as a low-risk group, with a risk of lymphogenous metastatic spread of
      only 1%. CONCLUSIONS: Well differentiated or moderately differentiated carcinomas
      having a diameter of less than 2 cm can be treated by local intervention, such as
      local excision or endoscopic removal, without any increase in risk, provided that
      the tumour is reliably removed without residual tumour (histologically confirmed
      R0). In the presence of an elevated surgical risk, the choice of treatment must
      be made on an individual basis.

PMID- 15498638
TI  - The role of PET scan in the preoperative management of oesophageal cancer.
AB  - AIM: The aim of this study was to evaluate the role of the 18F-FDG-PET in the
      preoperative evaluation of patients with oesophageal or gastro-oesophageal
      junction (GEJ) cancer and to define its impact on therapeutic management.
      PATIENTS AND METHODS: This study included 58 patients with biopsy proven
      oesophageal or GEJ cancer who underwent PET in addition to the conventional
      diagnostic work-up. The sensitivity, specificity and accuracy of CT and PET were
      calculated for detection of tumour and distant metastases. RESULTS: The
      sensitivity, specificity and accuracy of tumour detection were, respectively, 84,
      100 and 84% for CT and 87, 100 and 87% for PET (p=ns). PET permitted detection of
      distant metastases, which were not seen on CT in seven patients. In two patients,
      a second primary tumour was detected on PET. CONCLUSIONS: The sensitivity of PET
      for loco regional lymph nodes detection is low. The major clinical impact is the
      detection of distant metastases.

PMID- 15498639
TI  - Tumour endothelial marker 8 (TEM-8) in human colon cancer and its association
      with tumour progression.
AB  - BACKGROUND AND AIMS: Tumour endothelial marker-8 (TEM-8) is endothelial cell
      surface marker that may be specific to tumour endothelial cells. This study
      examined the role of TEM-8 in human colon cancer and its correlation with tumour
      prognosis. METHODOLOGY: Specimens of colorectal tissue (normal and cancer) were
      stained immunohistochemically with an anti-TEM-8 antibody, newly developed in our
      laboratory, and with anti-vonWillebrand Factor antibody. RNA was extracted from
      frozen sections for gene amplification. The anti-TEM-8 antibody specificity
      tested by using slot blotting with irrelevant antibody, and western blotting with
      different cell lines. The expression of TEM-8 was assessed using RT-PCR, and the
      level of TEM-8 was quantified using real-time-quantitative PCR (Q-RT-PCR).
      RESULTS: TEM-8 staining was primarily seen in endothelial cells. TEM-8 identified
      more micro-vessels in colon tumour tissue, than in normal colon tissues,
      (p=0.002). Whereas, fewer vessels were stained positive for TEM-8 in normal
      tissues stained positive for vonWillebrand Factor (factor-8), (p=0.008).
      Malignant cells in tumour tissues were found to be stained strongly positive for
      TEM-8 compared with the epithelial cells in normal colon tissues. The level of
      TEM-8 expression was significantly higher in the tumour tissues compared to the
      normal colon mucosa (p=0.001). TEM-8 mRNA expression was also found to be more
      elevated in patients with advanced tumour, Dukes C (Dukes A vs. Dukes C, p=0.01).
      CONCLUSION: TEM-8 is a marker that identifies tumour associated micro-vessels in
      colon cancer. The levels of expression of TEM-8 in invasive colon cancer are
      linked to disease progression. This suggests that TEM-8 has significant
      prognostic and therapeutic values in colon cancer.

PMID- 15498640
TI  - Treatment of locally recurrent rectal cancer, results and prognostic factors.
AB  - PURPOSE: Assessment of the results and prognostic factors in patients with
      locally recurrent rectal cancer treated with curative intent. PATIENTS AND
      METHODS: Forty patients with an isolated pelvic recurrence of rectal cancer were
      studied retrospectively. The treatment consisted of radiotherapy alone or
      combined with chemotherapy and/or surgery performed between January 1992 and July
      2001. Radiotherapy was given with a 3-4 fields technique (6-15 MV), five times a
      week. The median radiation dose was 50 Gy (range 25-66.6 Gy). Twenty-five
      patients underwent salvage surgery. Five patients were treated with concomitant
      chemotherapy (5-fluoro-uracil/leucovorin) (5FU/LV) during the 1st and 5th week of
      radiotherapy. RESULTS: Twenty-two of the 40 patients were male. The local
      recurrence free survival after 3 and 5 years, respectively, was 49 and 39%. Male
      gender was the only independent factor associated with failure of local control.
      The 3 and 5-year overall survival of the total group was 36 and 19%,
      respectively, with a median survival of 26 months. CONCLUSION: In a selection of
      patients in the treatment of locally recurrent rectal cancer valuable local
      palliation if not cure, can be reached. A multimodality approach seems to offer
      the best chances in this threatening situation.

PMID- 15498641
TI  - Revision of gastrointestinal mesenchymal tumours with CD117.
AB  - BACKGROUND: Tyrosinekinase inhibitors improve the treatment of gastrointestinal
      stromal tumours (GISTs) and their diagnosis has been facilitated by recently
      developed immunohistochemical markers. It is hypothesised that in the past, the
      true incidence of GISTs has been underestimated. AIMS: To study the
      clinicopathological features of previously resected mesenchymal tumours of the
      gastrointestinal tract and determine the accuracy of previous diagnostic results.
      PATIENTS AND METHODS: Patients with mesenchymal tumours of the gastrointestinal
      tract operated on between 1987 and 2002 were identified using medical and
      pathologic files. Immunohistochemical staining for CD117, CD34, desmin and S100
      was performed, and diagnosis reviewed. RESULTS: Thirty-six mesenchymal tumours
      were reanalysed. Before revision, diagnosis of GIST was correctly made in only
      six cases. Supportive use of immunohistochemical markers for accurate diagnosis
      of the remaining 30 previously undefined mesenchymal tumours yielded 17
      additional GISTs. Therefore, 23 of 36 (63%) gastrointestinal mesenchymal tumours
      were shown to be GISTs. CONCLUSIONS: The true incidence of GISTs has been
      underestimated. There is merit in reviewing the clinical diagnoses of all
      mesenchymal tumours of the gastrointestinal tract with modern immunohistochemical
      markers. This may enhance clinical decision making.

PMID- 15498642
TI  - Responders benefit from neoadjuvant radiochemotherapy in esophageal squamous cell
      carcinoma: results of a prospective phase-II trial.
AB  - BACKGROUND: We present the results of a prospective phase-II-study of neoadjuvant
      combined radiochemotherapy followed by surgical resection in patients with
      histological proven locally advanced squamous cell carcinoma of the esophagus
      located at or above the level of the tracheal bifurcation. METHODOLOGY: Between
      February 1995 and March 2000 a total of 76 patients with esophageal squamous cell
      carcinoma (uT3/4N0/+-categories) received simultaneous combined neoadjuvant
      radiochemotherapy consisting of a continuous intravenous infusion of 5
      fluorouracil (300 mg/m2/day) 7 day per week concurrently with conventional
      fractioned external beam radiation therapy (2 Gy/day), five fractions per week up
      to a total dose of 30 Gy. RESULTS: Radiochemotherapy related acute severe
      toxicity rate (CTC-grade-III) occurred in 34 patients, two patients died. Sixty
      four patients underwent surgery with a complete resection in 48 patients. Three
      patients died during a 90-day post-operative course. The histopathological workup
      revealed no viable residual tumour cells in eight patients (ypCR) and according
      to the modified criteria of Mandard in 26 patients a histopathological response.
      Twenty-two of these patients underwent a R0-resection. The median follow-up time
      was 5.4 years with an overall median survival time of 20.6 months. The median
      survival in the 26 responders was 32.3 months versus 19.5 months in 38 non
      responders (p=0.03). CONCLUSIONS: Patients with locally advanced squamous cell
      carcinoma of the esophagus, who respond to preoperative neoadjuvant combined
      radiochemotherapy, seem to have more benefit from subsequent resection than non
      responding patients.

PMID- 15498643
TI  - Pelvic exenteration and sphincter preservation in the treatment of soft tissue
      sarcomas.
AB  - BACKGROUND: Pelvic sarcomas are rare and there are very few effective therapeutic
      alternatives. A complete resection is considered the main factor associated to a
      good prognosis, which justifies the employment of a pelvic exenteration (PE) in
      selected cases. METHODS: Between 1980 and 2000, 96 PE were performed, nine of
      which were for sarcomas. The clinical characteristics, surgical and
      anatomopathological aspects and the patients' evolution were described. RESULTS:
      The median follow-up time was 24 months (ranging from 1 to 57 months). In
      relation to the sphincters preservation, at least one sphincter was preserved in
      five patients. There were two post-operative deaths. In the last follow-up, six
      patients were alive without any evidence of the disease. CONCLUSION: Pelvic
      exenterations should be performed for the treatment of selected cases of locally
      advanced pelvic sarcomas. Sphincter preservation may be performed, provided that
      oncological resection principles are obeyed.

PMID- 15498644
TI  - Prognosis of stage III or IV primary peritoneal serous papillary carcinoma.
AB  - AIMS: To study the prognosis of patients with stage IIIC/IV primary peritoneal
      serous papillary carcinoma (PSPC) (study group) compared with that of patients
      with epithelial ovarian carcinoma (EOC) (control group). METHODS: A retrospective
      case-control study including a study group of 37 patients who were matched with a
      control group of 37 patients. Patients were matched for the histologic subtype
      (serous tumor), tumor stage, tumor grade, residual disease at the end of
      debulking surgery (initial or interval) and age (+/-5 years). RESULTS: Debulking
      surgery was performed initially or at interval surgery in respectively, 10 and 27
      patients in the study group and 17 and 20 in the control group. All patients were
      treated with platinum-based chemotherapy (combined with paclitaxel in 33) in both
      groups. The overall survival rate at 3 years in the study and control groups was,
      respectively, 60% versus 55% (NS). However, event-free survival rates at 3 years
      (CI 95%) were statistically different (respectively, 29% in the study group
      versus 16% in the control group: p=0.008). CONCLUSIONS: Peritoneal disease is
      more bulky in patients with PSPC. Neoadjuvant chemotherapy is more often required
      to achieve optimal debulking surgery in PSPC. Overall survival of patients with
      PSPC is similar to that of their EOC counterparts. Thus, the management of PSPC
      should not be different from that of advanced stage EOC.

PMID- 15498645
TI  - Stewart-Treves syndrome--treatment and outcome in six patients from a single
      centre.
AB  - AIMS: Stewart-Treves syndrome is an angiosarcoma associated with long-standing
      lymphoedema, most commonly seen as a rare complication of breast cancer
      treatment, and is associated with a poor outcome. We present results from six
      patients supporting the use of early radical surgery to improve prognosis.
      METHODS: Six patients with Stewart-Treves syndrome were diagnosed and treated at
      our centre over an 11-year period. Five patients had forequarter amputation and
      the sixth had a through-hip amputation. RESULTS: Four of the six patients are
      alive and well following surgery (at 3, 16, 23, and 135 months after amputation);
      one patient died from metastatic disease at 15 months and the second died due to
      an unrelated malignancy. CONCLUSION: Early diagnosis and treatment by radical
      ablative surgery confers a reasonable prognosis with this rare but aggressive
      disease. A nihilistic approach is unjustified.

PMID- 15498646
TI  - Expression of proto-oncogene c-kit in high risk prostate cancer.
AB  - AIMS: We determined whether c-kit proto-oncogene is expressed in prostate cancer
      and whether its expression is related with biochemical relapse in high risk
      localized prostate cancer patients. METHODS: c-Kit expression was evaluated by
      immuno-histochemistry in 94 prostate cancer samples from patients treated by
      radical prostatectomy followed by adjuvant hormonal therapy because all patients
      had a pT3a stage (initially cT2 stage). All patients presented a >7 Gleason score
      and a >10 pre-operative PSA value. We evaluated association between c-kit
      positive staining and disease free survival. RESULTS: In 26 of 94 prostate
      cancer, we found an epithelial positive c-kit expression. The epithelial
      expression was found in the peripheral zone of prostate tissue. 13/94 relapsed
      and, although not statistically significant (p 0.055), a trend to a higher risk
      of relapse among the c-kit positive samples was observed in our series of
      prostate cancer patients. CONCLUSIONS: Our study is only an initial experience
      and it is necessary to consider a higher number of patients to clarify whether c
      kit is really an independent predictor for disease recurrence. Further study in
      this area will help to understand whether anti c-kit drugs could become an
      effective complement to the armamentarium of prostate cancer therapies.

PMID- 15498647
TI  - Breast cancer bone metastasis in femur: surgical considerations and
      reconstruction with Long Gamma Nail.
AB  - AIM: The femur is the most common long bone involved in metastatic breast cancer.
      Several studies have been published on the surgical management of metastatic
      disease of the femur. However, only few studies have been published specifically
      on the outcomes following reconstruction of femoral metastasis from breast cancer
      using a third generation intramedullary nail. The aim of this study is to review
      the outcomes after intramedullary surgical stabilization of femoral metastases
      from breast cancer. This is often associated with significant bone destruction.
      METHODS: A retrospective study of 18 femoral metastatic lesions in 15 patients
      treated with a Long Gamma Nail over a 6-year period was carried out. Pain relief,
      mobilization status and implant related complications were the main outcome
      measures analyzed. RESULTS: Thirteen out of 15 patients had complete pain relief
      and all patients regained their preoperative mobilization status with or without
      walking aids. There were no implant failures or perioperative deaths. Four (26%)
      patients developed minor complications. Ten patients died with an average
      survival of 9 months and five patients are alive with an average survival of 32
      months. CONCLUSION: Stabilization of femoral metastases due to breast cancer with
      Long Gamma Nail is a safe and effective method with acceptable risks.

PMID- 15498648
TI  - Ameloblastomas of the jaws: clinico-pathological review of 11 patients.
AB  - AIMS: The ameloblastoma is an uncommon benign odontogenic neoplasm of the
      maxillofacial region constituting less than 1% of tumours of the oral cavity. The
      purpose of this paper is to discuss and evaluate the surgical treatment and the
      outcome from a series of 11 patients with ameloblastomas. METHODS: Between the
      years 1995 and 2003, 11 patients (eight female and three male) aged 17-86 years
      (mean 52.7) suffering from ameloblastomas of the jaws were seen in our
      Department. RESULTS: Ten patients were treated surgically. In eight of those
      radical surgery was applied. Patients with maxillary tumours were subjected to
      hemimaxillectomy and local excision. Radical treatment with segmental resection
      of the mandible was performed in six patients with multilocular (solid)
      mandibular ameloblastomas, with immediate reconstruction of the defect. Follow-up
      ranged from 3 months to 7.5 years. CONCLUSION: Multilocular (solid) type of
      tumours should be approached with radical surgical treatment. Enucleation and
      rarely marsupialization can be applied selectively to unilocular ameloblastomas.

PMID- 15498649
TI  - Is there any place for the N/T quotient as a prognostic factor in breast cancer?

PMID- 15498650
TI  - d(G3T4G4) forms unusual dimeric G-quadruplex structure with the same general fold
      in the presence of K+, Na+ or NH4+ ions.
AB  - We have recently communicated that DNA oligonucleotide d(G(3)T(4)G(4)) forms a
      dimeric G-quadruplex in the presence of K(+) ions [J. Am. Chem. Soc.2003, 125,
      7866-7871]. The high-resolution NMR structure of d(G(3)T(4)G(4))(2) G-quadruplex
      exhibits G-quadruplex core consisting of three stacked G-quartets. The two
      overhanging G3 and G11 residues are located at the opposite sides of the end G
      quartets and are not involved in G-quartet formation. d(G(3)T(4)G(4))(2) G
      quadruplex represents the first bimolecular G-quadruplex where end G-quartets are
      spanned by diagonal (T4-T7) as well as edge-type loops (T15-T18). Three of the G
      rich strands are parallel while one is anti-parallel. The G12-G22 strand
      demonstrates a sharp reversal in strand direction between residues G19 and G20
      that is accommodated with the leap over the middle G-quartet. The reversal in
      strand direction is achieved without any extra intervening residues. Here we
      furthermore examined the influence of different monovalent cations on the folding
      of d(G(3)T(4)G(4)). The resolved imino and aromatic proton resonances as well as
      (sequential) NOE connectivity patterns showed only minor differences in key intra
      and interquartet NOE intensities in the presence of K(+), Na(+) and NH(4)(+)
      ions, which were consistent with subtle structural differences while retaining
      the same folding topology of d(G(3)T(4)G(4))(2) G-quadruplex.

PMID- 15498651
TI  - Synthesis and antimalarial activity of 6-cycloalkylvinyl substituted 1,2,4
      trioxanes.
AB  - 6-Cycloalkylvinyl substituted 1,2,4-trioxanes 6-15 have been prepared and tested
      against multi-drug resistant Plasmodium yoelii in mice. The most active trioxane
      11 provides 80% protection to the treated mice. Further derivatization of 11
      leads to decrease in antimalarial activity.

PMID- 15498652
TI  - ATP-phosphopeptide conjugates as inhibitors of Src tyrosine kinases.
AB  - A number of Src SH2 domain inhibitors enhance the kinase catalytic activity by
      switching the closed inactive to the open active conformation. ATP-phosphopeptide
      conjugates were designed and synthesized as Src tyrosine kinase inhibitors based
      on a tetrapeptide sequence pTyr-Glu-Glu-Ile (pYEEI) and ATP to block the SH2
      domain signaling and substrate phosphorylation by ATP, respectively. In general,
      ATP-phosphopeptide conjugates with optimal linkers such as compounds 5 and 7
      (K(i) = 1.7-2.6 microM) showed higher binding affinities to the ATP-binding site
      relative to the other ATP-phosphopeptide conjugates having short or long linkers,
      1-4 and 6, (K(i) = 10.1-16.1 microM) and ATP (K(m) = 74 microM). These ATP
      phosphopeptide conjugates may serve as novel templates for designing protein
      tyrosine kinase inhibitors to block SH2 mediated protein-protein interactions and
      to counter the activation of enzyme that resulted from the SH2 inhibition.

PMID- 15498653
TI  - Inclusion complexes of paclitaxel and oligo(ethylenediamino) bridged bis(beta
      cyclodextrin)s: solubilization and antitumor activity.
AB  - The inclusion complexation behavior of paclitaxel with a series of
      oligo(ethylenediamino) bridged bis(beta-cyclodextrin)s possessing bridge chains
      in different length (1-4) has been investigated in order to improve the water
      solubility of paclitaxel. It is found that only the long-tethered bis(beta
      cyclodextrin)s 1 and 2 can form the inclusion complexes with paclitaxel, which
      are characterized by NMR, SEM, XRD, FT-IR, TG-DTA, DSC, and microcalorimetry
      technology. The results obtained show that bis(beta-cyclodextrin)s 1 and 2 are
      able to solubilize paclitaxel to high levels up to 2 and 0.9 mg/mL, respectively.
      The high complex stability of bis(beta-cyclodextrin) 1 and paclitaxel is
      discussed from thermodynamic viewpoint. Furthermore, the cytotoxicity of these
      complexes assessed using a human erythroleukemia K562 cell line indicates that
      the IC(50) value of 1/paclitaxel complex is 6.0 x 10(-10) mol/dm(3) (calculated
      as paclitaxel molar concentration), which means that the antitumor activity of
      1/paclitaxel complex is better than that of parent paclitaxel (IC(50) value 9.8 x
      10(-10) mol/dm(3)). This high antitumor activity, along with the satisfactory
      water solubility and high thermal stability of the 1/paclitaxel complex, will be
      potentially useful for its clinical application as a highly effective antitumor
      drug.

PMID- 15498654
TI  - Chlamydocin-hydroxamic acid analogues as histone deacetylase inhibitors.
AB  - Chlamydocin-hydroxamic acid analogues were designed and synthesized as histone
      deacetylase (HDAC) inhibitors based on the structure and HDAC inhibitory activity
      of chlamydocin and trichostatin A. Chlamydocin is a cyclic tetrapeptide
      containing an epoxyketone moiety in the side chain that makes it an irreversible
      inhibitor of HDAC. We replaced the epoxyketone moiety of chlamydocin with
      hydroxamic acid to design potent and reversible inhibitors of HDAC. In addition,
      a number of amino-cycloalkanecarboxylic acids (Acc) are introduced instead of the
      simple amino-isobutric acid (Aib) for a variety of the series of chlamydocin
      analogues. The compounds synthesized were tested for HDAC inhibitory activity and
      the results showed that many of them are potent inhibitors of HDAC. The
      replacement of Aib residue of chlamydocin with an aromatic amino acid enhances
      the in vivo and in vitro inhibitory activity. We have carried out circular
      dichroism and molecular modeling studies on chlamydocin-hydroxamic acid analogue
      and compared it with the solution structure of chlamydocin.

PMID- 15498655
TI  - Synthesis and protein conjugation studies of vitamin K analogues.
AB  - Two vitamin K analogues bearing a carboxylic acid side chain (9a and its
      deuterated analogue 9b) were each synthesised in six steps from commercially
      available menadione. Analogue 9b was conjugated to lysozyme and bovine serum
      albumin (BSA) using EDCI/HOBT and by prior formation of its activated
      succinimidyl ester 11. Quantification of the thus formed conjugates by ESMS and
      LC-MS revealed that the number of equivalents of the analogue used in the
      couplings systematically controls the number of analogues that conjugate to the
      protein.

PMID- 15498656
TI  - Preferential target is mitochondria in alpha-mangostin-induced apoptosis in human
      leukemia HL60 cells.
AB  - Our previous study has shown that alpha-mangostin, a xanthone from the pericarps
      of mangosteen, induces caspase-3-dependent apoptosis in HL60 cells. In the
      current study, we investigated the mechanism of apoptosis induced by alpha
      mangostin in HL60 cells. Alpha-mangostin-treated HL60 cells demonstrated caspase
      9 and -3 activation but not -8, which leads us to assume that alpha-mangostin may
      mediate the mitochondrial pathway in the apoptosis. Parameters of mitochondrial
      dysfunction including swelling, loss of membrane potential (deltapsim), decrease
      in intracellular ATP, ROS accumulation, and cytochrome c/AIF release, were
      observed within 1 or 2 h after the treatment. On the other hand, alpha-mangostin
      treatment did not affect expression of bcl-2 family proteins and activation of
      MAP kinases. These findings indicate that alpha-mangostin preferentially targets
      mitochondria in the early phase, resulting in indication of apoptosis in HL60
      cells. Furthermore, we examined the structure-activity relationship between
      xanthone derivatives including alpha-mangostin and the potency of deltapsim-loss
      in HL60 cells. Interestingly, replacement of hydroxyl group by methoxy group
      remarkably decreased its potency. It was also shown that the cytotoxicity
      substantially correlated with deltapsim decrease. These results indicate that
      alpha-mangostin and its analogs would be candidates for preventive and
      therapeutic application for cancer treatment.

PMID- 15498657
TI  - Novel imidazole substituted 6-methylidene-penems as broad-spectrum beta-lactamase
      inhibitors.
AB  - Beta-lactamases are serine and metallo-dependent enzymes produced by the bacteria
      in defense against beta-lactam antibiotics. Production of class-A, class-B, and
      class-C enzymes by the bacteria make the use of beta-lactam antibiotics
      ineffective in certain cases. To overcome resistance to beta-lactam antibiotics,
      several beta-lactamase inhibitors such as clavulanic acid, sulbactam, and
      tazobactam are widely used in the clinic in combination with beta-lactam
      antibiotics. However, single point mutations within these enzymes have allowed
      bacteria to overcome the inhibitory effect of the commercially approved beta
      lactamase inhibitors. Although the commercially available beta-lactamase
      inhibitor/beta-lactam antibiotic combinations are effective against class-A
      producing bacteria and many extended spectrum beta-lactamase (ESBL's) producing
      bacteria they are less effective against class-C enzymes expressing bacteria. To
      circumvent this problem, based on modeling studies several novel imidazole
      substituted 6-methylidene-penem derivatives were synthesized and tested against
      various beta-lactamase producing isolates. The present paper deals with the
      synthesis and structure-activity relationships (SAR) of these compounds.

PMID- 15498658
TI  - A mechanistic study of 3-aminoindazole cyclic urea HIV-1 protease inhibitors
      using comparative QSAR.
AB  - Comparative QSAR studies on P2/P2' and P1/P1' substituted symmetrical and
      nonsymmetrical 3-aminoindazole cyclic urea HIV-1 protease inhibitors were
      performed. The protease inhibitory activity of these compounds was found to
      decrease with larger and more hydrophobic molecules, whereas the antiviral
      potency and translation across the cell membrane increases with increase in
      hydrophobicity and size. These results provide mechanistic insight about the mode
      of interaction of these compounds with HIV-1 protease receptor and would help in
      further improving the biological activity.

PMID- 15498659
TI  - In silico prediction of central nervous system activity of compounds.
      Identification of potential pharmacophores by the TOPS-MODE approach.
AB  - The central nervous system (CNS) activity has been investigated by using a
      topological substructural molecular approach (TOPS-MODE). A discriminant analysis
      to classify CNS and non-CNS drugs was developed on a data set (302 compounds) of
      great structural variability where more than 81% (247/302) were well classified.
      Randic's orthogonalization procedures was carried out to allow the interpretation
      of the model and to avoid the collinearity among descriptors. The discriminant
      model was assessed by a leave-n-out (when n varies from 2 to 20) cross-validation
      procedure (79.94% of correct classification), an external prediction set composed
      by 78 CNS/non-CNS drugs (80.77% of correct classification) and a 5-fold full
      cross-validation (removing 78 compounds in each cycle, 80.00% of good
      classification). With this methodology was demonstrated that the hydrophobicity
      increase the CNS activity, while the dipole moment and the polar surface area
      decrease it; evidencing the capacity of the TOPS-MODE descriptors to estimate CNS
      activity for new drug candidates. The structural contributions to the CNS
      activity for two compounds are presented on the basis of fragment contributions.
      The model has also been able to identify potential structural pharmacophore,
      showing its possibilities in the lead generation and optimization processes.

PMID- 15498660
TI  - Synthesis and evaluation of N-aryl and N-alkenyl CBI derivatives.
AB  - The preparation of a novel series of N-aryl CBI derivatives in which an aryl
      substituent could be used to predictably modulate the reactivity of the resulting
      CC-1065/duocarmycin alkylation subunit analogue is detailed and its extension to
      a unique series of N-alkenyl derivatives is reported. The N-aryl derivatives were
      found to be exceptionally stable and to exhibit well-defined relationships
      between structure (X-ray), reactivity, and cytotoxic potency. When combined with
      the results of past investigations, the studies define a fundamental parabolic
      relationship between reactivity and cytotoxic potency. The parabolic relationship
      establishes that compounds in the series should possess sufficient stability to
      reach their biological target (DNA), yet maintain sufficient reactivity to
      effectively alkylate DNA upon reaching the biological target. Just as
      importantly, it defined this optimal balance of stability and reactivity that may
      be used for future design of related analogues. Notably, the duocarmycin SA and
      yatakemycin alkylation subunit lies at this optimal stability/reactivity
      position, whereas the CC-1065 and duocarmycin A alkylation subunits lie
      progressively and significantly to the left of this optimal position (too
      reactive).

PMID- 15498661
TI  - Synthesis and antihyperglycemic activity profiles of novel thiazolidinedione
      derivatives.
AB  - A number of thiazolidine-2,4-diones derivatives having carboxylic ester appendage
      at N-3 were synthesized and their antihyperglycemic activity was evaluated. Many
      of these derivatives as well as their corresponding carboxylic acid showed
      significant improvement on post-prandial hyperglycemia in normal rats, in
      contrast to their poor agonist activity at PPARgamma.

PMID- 15498662
TI  - Design, synthesis and biological evaluation of novel non-nucleoside HIV-1 reverse
      transcriptase inhibitors with broad-spectrum chemotherapeutic properties.
AB  - Acquired immunodeficiency syndrome (AIDS) results from infection by the
      retrovirus, human immunodeficiency virus (HIV). HIV is the most significant risk
      factor for many opportunistic infections like tuberculosis, hepatitis, bacterial
      infections, etc. In this paper, we designed aminopyrimidinimino isatin lead
      compound as a novel non-nucleoside reverse transcriptase inhibitor with broad
      spectrum chemotherapeutic properties for the effective treatment of AIDS and AIDS
      related opportunistic infections. Compound 1-ethyl-6-fluoro-1,4-dihydro-4-oxo
      7[[N(4)-[3'-(4'-amino-5'-trimethoxybenzylpyrimidin-2'-yl)imino-1'-(5
      fluoroisatinyl)]methyl]-N(1)-piperazinyl]-3-quinoline carboxylic acid (12)
      emerged as the most potent broad-spectrum chemotherapeutic agent active against
      HIV, HCV, Mycobacterium tuberculosis and various pathogenic bacteria.

PMID- 15498663
TI  - Synthesis of an artificial hole-transporting nucleoside triphosphate, dMDATP, and
      its enzymatic incorporation into DNA.
AB  - We report on the enzymatic synthesis of DNA wires by successive incorporation of
      artificial nucleotides. We synthesized an efficient hole-transporting nucleoside
      triphosphate, d(MD)ATP, and have examined the screening of polymerases and
      reverse transcriptases for enzymatic incorporation of d(MD)ATP into DNA. We found
      that KOD Dash is an effective enzyme for the enzymatic synthesis of (MD)A
      containing DNA. Furthermore, the efficiency of enzymatic incorporation was
      remarkably improved by the addition of manganese chloride. By applying the PCR
      method to the synthesis of DNA containing a run of (MD)A, the (MD)A run was
      amplified up to 6 x 10(6) times. (MD)A runs prepared by the enzymatic method
      exhibited a high hole-transporting ability.

PMID- 15498664
TI  - Stereoselective synthesis and antifungal activity of (Z)-trans-3-azolyl-2
      methylchromanone oxime ethers.
AB  - A series of (Z)-trans-3-azolyl-2-methylchromanone oxime ethers were
      stereoselectively synthesized and tested for in vitro antifungal activity. Many
      of these derivatives exhibit high activity against Candida albicans,
      Saccharomyces cerevisiae, Aspergillus niger, and Microsporum gypseum.

PMID- 15498665
TI  - Anti-allergic principles from Thai zedoary: structural requirements of
      curcuminoids for inhibition of degranulation and effect on the release of TNF
      alpha and IL-4 in RBL-2H3 cells.
AB  - The 80% aqueous acetone extract of the rhizomes of Curcuma zedoaria cultivated in
      Thailand (Thai zedoary) was found to inhibit release of beta-hexosaminidase, as a
      marker of antigen-IgE-mediated degranulation, in RBL-2H3 cells and passive
      cutaneous anaphylaxis reaction in mice. From the active fraction, four
      curcuminoids (curcumin, dihydrocurcumin, tetrahydrodemethoxycurcumin, and
      tetrahydrobisdemethoxycurcumin) were isolated together with two bisabolane-type
      sesquiterpenes, and the effects of four curcuminoids from Thai zedoary and
      several related compounds on the degranulation were examined. Among them,
      curcumin showed the highest activity against beta-hexosaminidase release with
      IC(50) of 5.3 microM, followed by bisdemethoxycurcumin (IC(50) = 11 microM). With
      regard to the structural requirements of curcuminoids for the activity, the
      conjugated olefins at the 1-7 positions and the 4'- or 4''-hydroxyl groups of
      curcuminoids were suggested to be essential for the strong activity, whereas the
      3'- or 3''-methoxyl group only enhanced the activity. Furthermore, effects of
      curcumin and bisdemethoxycurcumin on calcium ionophores (A23187 and ionomycin)
      induced degranulation and antigen-induced release of TNF-alpha and IL-4 were
      examined.

PMID- 15498666
TI  - Synthesis and biological evaluation of novel propylamine derivatives as orally
      active squalene synthase inhibitors.
AB  - Squalene synthase inhibitors are potentially superior hypolipidemic agents. We
      synthesized novel propylamine derivatives, as well as evaluated their ability to
      inhibit squalene synthase and their lipid-lowering effects in rats. 1-Allyl-2-[3
      (benzylamino)propoxy]-9H-carbazole (YM-75440) demonstrated potent inhibition of
      the enzyme derived from HepG2 cells with an IC(50) value of 63 nM. It
      significantly reduced both plasma total cholesterol and plasma triglyceride
      levels following oral dosing to rats with a reduced tendency to elevate plasma
      transaminase levels.

PMID- 15498667
TI  - Synthesis and antibacterial activity of oxazolidinones containing pyridine
      substituted with heteroaromatic ring.
AB  - A series of oxazolidinone derivatives, which morpholino group of linezolid was
      replaced with heteroaromatic ring substituted pyridine moiety, were newly
      synthesized, and their substituted effects on in vitro and in vivo antibacterial
      activities were evaluated against four problematic gram-positive strains
      including drug resistant strains and two gram-negative strains. Most compounds
      exhibited the enhanced in vitro activities with 4-16-fold and three compounds
      exerted more than 2-fold increased in vivo efficacies than linezolid.

PMID- 15498668
TI  - Remarkably different structures and reaction mechanisms of ketoreductases for the
      opposite stereochemical control in the biosynthesis of BIQ antibiotics.
AB  - Two ketoreductases, RED1 and RED2, are involved in the biosynthesis of
      actinorhodin in Streptomyces coelicolor A3(2) and dihydrogranaticin in S.
      violaceoruber Tu22, respectively. They are responsible for the stereospecific
      reductions of the bicyclic intermediate to give (S)- or (R)-DNPA, although there
      is no similarity between their amino acid sequences. Biotransformation using
      synthetic analogous substrates revealed that the substrate specificities are
      quite different. Homology modelling studies and site directed mutagenesis showed
      remarkable differences in three-dimensional structures and catalytic mechanisms
      between RED1 and RED2.

PMID- 15498669
TI  - Design and synthesis of acyclic triaryl (Z)-olefins: a novel class of
      cyclooxygenase-2 (COX-2) inhibitors.
AB  - A group of acyclic 2-alkyl-1,1-diphenyl-2-(4-methylsulfonylphenyl)ethenes was
      designed for evaluation as selective cyclooxygenase-2 (COX-2) inhibitors. In
      vitro COX-1 and COX-2 isozyme inhibition structure-activity studies identified
      1,1-diphenyl-2-(4-methylsulfonylphenyl)hex-1-ene as a highly potent (IC(50) =
      0.014 microM), and an extremely selective [COX-2 selectivity index (SI) > 7142],
      COX-2 inhibitor that showed superior anti-inflammatory (AI) activity (ID(50) =
      2.5 mg/kg) relative to celecoxib (ID(50) = 10.8 mg/kg). This initial study was
      extended to include the design of a structurally related group of acyclic triaryl
      (Z)-olefins possessing an acetoxy (OAc) substituent at the para-position of the C
      1 phenyl ring that is cis to a C-2 4-methylsulfonylphenyl substituent. COX-1 and
      COX-2 inhibition studies showed that (Z)-1-(4-acetoxyphenyl)-1-phenyl-2-(4
      methylsulfonylphenyl)but-1-ene [(Z)-13b] is a potent (COX-1 IC(50) = 2.4 microM;
      COX-2 IC(50) = 0.03 microM), and selective (COX-2 SI = 81), COX-2 inhibitor which
      is a potent AI agent (ID(50) = 4.1mg/kg) with equipotent analgesic activity to
      celecoxib. A molecular modeling (docking) study showed that the SO(2)Me
      substituent of (Z)-13b inserts deep inside the 2 degrees -pocket of the COX-2
      active site, where one of the O-atoms of SO(2) group undergoes a H-bonding
      interaction with Phe(518). The p-OAc substituent on the C-1 phenyl ring is
      oriented in a hydrophobic pocket comprised of Met(522), Gly(526), Trp(387),
      Tyr(348), and Tyr(385), and the C-2 ethyl substituent is oriented towards the
      mouth of the COX-2 channel in the vicinity of amino acid residues Arg(120),
      Leu(531), and Val(349). Structure-activity data acquired indicate that a (Z)
      olefin having cis C-1 4-acetoxyphenyl (phenyl) and C-2 4-methylsulfonylphenyl
      substituents, and a C-1 phenyl substituent in conjunction with either a C-2
      hydrogen or short alkyl substituent provides a novel template to design acyclic
      olefinic COX-2 inhibitors that, like aspirin, have the potential to acetylate COX
      2.

PMID- 15498670
TI  - Synthesis and biological evaluation of indazolo[4,3-bc][1,5]naphthyridines (10
      aza-pyrazolo[3,4,5-kl]acridines): a new class of antitumor agents.
AB  - A series of potential DNA-binding antitumor agents, 2-[omega-(alkylamino)alkyl]-9
      methoxy-5-nitro-2,6-dihydroindazolo[4,3-bc][1,5]naphthyridines (2a-f), 10-aza
      derivatives of PZA, has been prepared by condensation of 9-chloro-2-methoxy-6
      nitro-5,10-dihydrobenzo[b][1,5]naphthyridin-10-one (6) with the appropriate
      (omega-aminoalkyl)hydrazine in tetrahydrofuran/methanol. Compound 6 was obtained
      by heating at 100 degrees C in H(2)SO(4)5, yielded by the condensation of 2,6
      dichloro-3-nitrobenzoic acid (4) and 6-methoxy-3-pyridinamine (3). The non
      covalent DNA-binding properties of 2 have been examined using a fluorometric
      technique. In vitro cytotoxic potencies of these derivatives against human
      hormone-refractory prostate adenocarcinoma cell line (PC-3) are described and
      compared to that of parent drug PZA. We selected the most cytotoxic target
      derivatives 2c,d, the in vitro inactive 2f, and reference compound PZA to
      investigate whether in vitro treatment with these drugs was able to induce
      necrotic and/or apoptotic cell death. To this purpose, we evaluated the
      percentage of apoptotic cells in PC-3 treated with the target compounds 2c,d,f
      and reference compound PZA, by Annexin V staining and Propidium iodide
      (PI)/Annexin V, biparametric flow cytometric analysis and agarose gel
      electrophoresis.

PMID- 15498671
TI  - Photo-caged agonists of the nuclear receptors RARgamma and TRbeta provide unique
      time-dependent gene expression profiles for light-activated gene patterning.
AB  - Light-activated gene expression systems hold promise as new tools for studying
      spatial and temporal gene patterning in multicellular systems. Photo-caged forms
      of nuclear receptor agonists have recently been shown to mediate photo-dependent
      transcription in mammalian cells, however, because intracellularly released
      agonists can rapidly diffuse out of cells, the photo-initiated transcription
      response is only transient and limited to only a few hours in reported examples.
      Herein we describe a photo-caged thyroid hormone receptor agonist that provides a
      robust 36 h transcription response to a single irradiation event. These findings
      are in contrast to a closely related system, which uses a caged retinoic acid
      receptor agonist, which provides only a short transcription response. Comparison
      of the two systems, show that the duration of transcription response is not
      controlled by the rate of diffusion of free ligand out of the cell, but perhaps
      by the duration of ligand-induced transcription/stability of the active
      transcription complex.

PMID- 15498672
TI  - Synthesis and biological evaluation of new derivatives of emodin.
AB  - Drugs containing an anthraquinone moiety such as daunorubicin (Daunoblastin) and
      mitoxantrone (Onkotrone) constitute some of the most powerful cytostatics. They
      suppress tumor growth mainly by intercalation into DNA and inhibition of
      topoisomerase II, and are suspected to generate free radicals leading to DNA
      strand scission. We established a novel strategy for obtaining new highly
      functionalized derivatives of emodin (1,3,8-trihydroxy-6-methyl-anthraquinone).
      Using emodin, DIB, and an appropriate amine as starting materials, we obtained a
      wide range of emodin-related structures by one-pot synthesis. Several of these
      derivatives showed stronger cytotoxic and cytostatic activity than emodin. In
      particular, compound 6 was highly effective on the HepG2 tumor cell line, but did
      not show any cytotoxicity on normal hepatocytes. In addition to this favorable
      feature, compound 6 revealed interesting binding properties to a recombinant
      fragment of the multi-drug-resistance transporter, pgp, and reversed the multi
      drug-resistance phenotype of H4-II-E cells, thus making this compound a promising
      potential anti-tumor drug.

PMID- 15498673
TI  - Catalytic transformations with copper-metalated diglycine conjugates.
AB  - A series of copper-metalated, water-soluble bis-diglycine conjugates were
      synthesized and characterized through spectroscopic methods. These conjugates
      were evaluated for the cleavage of phosphodiester substrates, supercoiled plasmid
      relaxation in the presence of co-oxidants, and for the oxidation of a diphenolic
      substrate, 2,6-dimethoxyphenol. Appreciable rate enhancements were observed for
      these reactions and the oxidative nucleolytic cleavage activity and phenol
      oxidative coupling was presumably manifested via formation of reactive oxygen
      species.

PMID- 15498674
TI  - Synthesis and biological evaluation of some 6-arylamidomorphines as analogues of
      morphine-6-glucuronide.
AB  - A series of 6-beta-arylamidomorphines was synthesized and biologically evaluated.
      Various aryl substituents were introduced into the arylamidomorphines to examine
      substituent structure-activity relationships. Competition binding assays showed
      that compounds 10a-h bound to the mu opioid receptor with high affinity (0.2-0.6
      nM). Functional assays showed that compounds 10a-h acted as full mu opioid
      receptor agonists. The ED(50) of compound 10e.HCl as an analgesic was 12.6 mg/kg
      in the tail flick latency test in the rat.

PMID- 15498675
TI  - Scabrosin esters and derivatives: chemical derivatization studies and biological
      evaluation.
AB  - Several derivatives of the natural scabrosin esters were synthesized in order to
      elucidate the structural features present, which are responsible for the
      biological activities. The studies demonstrate that full anti-proliferative
      activities of the scabrosin esters, both the carboskeleton core as well as the
      ability to form the dithiol and/or the disulfide linkage of the
      epidithiopiperazine-2,5-dione are required. The presence of the epoxide rings on
      the scabrosin esters do not contribute to the observed biological activities.

PMID- 15498676
TI  - Elucidation of structure-activity relationships for 2- or 6-substituted-5,8
      dimethoxy-1,4-naphthoquinones.
AB  - 1,4-Naphthoquinones have already been recognized to possess a wide range of
      biological activities. We have developed quantitative structure activity
      relationships (QSAR) for different series of 2- or 6-substituted-5,8-dimethoxy
      1,4-naphthoquinones to understand the chemical-biological interaction governing
      antiproliferative/cytotoxic activities against L1210 cells. QSAR results have
      shown that these activities of 2- or 6-substituted-5,8-dimethoxy-1,4
      naphthoquinones depend largely on their hydrophobicity.

PMID- 15498677
TI  - Stereoselective inhibition of glutamate carboxypeptidase by organophosphorus
      derivatives of glutamic acid.
AB  - A series of alkyl and aryl phosphonyl, thiophosphonyl, and dithiophosphonyl
      derivatives of (S)- and (R)-glutamic acid were prepared and examined for
      inhibitory potency against glutamate carboxypeptidase (carboxypeptidase G). The
      acquisition of the phosphonamidodithioic acids and the individual
      phosphonamidothioic acid diastereomers was achieved through a common
      phosphonamidothiolate precursor, which also allowed for the chromatographic
      resolution of the chiral phosphorus center of the phosphonamidothioic acids. The
      most potent inhibitor of the series was the n-butylphosphonamidate derivative of
      the natural isomer of glutamic acid. Although each diastereomeric pair of three
      phosphonamidothionates exhibited stereoselective inhibition consistent with the
      configuration of the chiral phosphorus center, this effect was generally not
      remarkable. More important, was the effect of carbon stereochemistry upon
      glutamate carboxypeptidase inhibition as exemplified by a limited series of
      enantiomeric pairs of phosphonamidate and phosphonamidodithionate derivatives of
      glutamic acid. The phosphonamidate analogs derived from the unnatural
      stereoisomer of glutamic acid were devoid of inhibitory potency in contrast to
      their enantiomers. Surprisingly, the phosphonamidodithionates derived from the
      unnatural stereoisomer of glutamic acid demonstrated greater inhibitory potency
      than their naturally-derived antipodes.

PMID- 15498678
TI  - Sorption and desorption of radioselenium on calcareous soil and its solid
      components studied by batch and column experiments.
AB  - The effect of different calcareous soil solid components on the sorption and
      desorption of radioselenium was investigated by using a selective extraction
      method. The distribution coefficients, the breakthrough curves and the
      displacement curves were experimentally determined by batch and column
      experiments. The experiments were carried out at pH 7.8 +/- 0.2, T=20 +/- 1
      degrees C and in the presence of 0.001 M CaCl2. It is found that all sorption
      isotherms are linear, the sorption-desorption hysteresis for untreated and
      treated soils to remove organic matter, CaCO3 and organic matter plus CaCO3 is
      obvious; and the retention of radioselenium can probably be attributed to clay
      and oxides. The contributions of organic matter and CaCO3 to the sorption of
      radioselenium are significant, and the interaction effects among organic matter,
      CaCO3 and other components play an important role in the sorption of
      radioselenium in calcareous soil. The content of interlaminary space of compacted
      soil plays an important role in the sorption of radioselenium in compacted soil.
      The presence of CaCO3 retards the transport of radioselenium in soils, CaCO3 is
      an important trap of radioselenium. It is very difficult for the effluent
      concentration to reach the influent concentration, although radioselenium is very
      quickly detected in the effluent solution. The breakthrough curves (BTCs) can be
      simulated by a one-dimensional convection-dispersion transport model.

PMID- 15498679
TI  - Half-life determination of 88Y and 89Sr.
AB  - Half-life measurements have been carried out at LNHB for 88Y using a 4pi gamma
      ionisation chamber and for 89Sr using a proportional counter. The determined half
      life values and associated standard uncertainties are 106.63 +/- 0.05 d for 88Y
      and 50.65 +/- 0.05 d for 89Sr, being consistent with relevant values reported in
      literature. Based on the present results and relevant literature values revised
      recommended half-life values and associated standard uncertainties are proposed,
      viz. 106.626 +/- 0.021 d for 88Y and 50.57 +/- 0.03 d for 89Sr.

PMID- 15498680
TI  - Facile access to 154Eu, a new reference source for calibration in gamma ray
      spectrometry.
AB  - Europium-154 can be obtained as a by-product from the large-scale production of
      Samarium-153 and possesses attractive features (t1/2 8.592 yr; Egamma 0.12-1.6
      MeV) for use as a reference source similar to 152Eu (t1/2 13.516 yr; Egamma 0.12
      1.4 MeV), which is the gold standard for calibration in gamma ray spectrometry.
      Thermal neutron irradiation of 5mg of 98% enriched 153Sm2O3 target in the reactor
      led to approximately 200 GBq 153Sm and 1.26 MBq 154Eu. A typical batch control
      sample of 153SmCl3 solution and final radiopharmaceutical product formulation of
      153Sm-phosphonate (153Sm-EDTMP) pooled together contained about 20% of total
      yield, requiring post decay disposal of 153Sm as radioactive waste. Such spent
      solutions pooled on quarterly basis led to availing 756 kBq of 154Eu. The
      radioactivity content and radionuclide purity (approximately 82%) of the
      recovered 154Eu sample were envisaged as adequate to prepare reference sources
      for calibration of gamma ray spectrometers. At present, one batch of 153Sm is
      handled per month at our institution, with the possibility for weekly processing
      in future. Access to approximately 3.5 MBq of 154Eu on quarterly basis is
      envisaged, apart from obviating the need for instituting steps to tackle disposal
      of the long-lived 154Eu in the spent solution. Up to 60-120 units of 20-100 kBq
      of 154Eu reference sources per year could thus be available by the proposed
      strategy.

PMID- 15498681
TI  - Application of deuteron-deuteron (D-D) fusion neutrons to 40Ar/39Ar
      geochronology.
AB  - Neutron irradiation of samples for 40Ar/39Ar dating in a 235U fission reactor
      requires error-producing corrections for the argon isotopes created from Ca, K,
      and, to a lesser extent, Cl. The fission spectrum includes neutrons with energies
      above 2-3 MeV, which are not optimal for the 39K(n,p)39Ar reaction. These higher
      energy neutrons are responsible for the largest recoil displacements, which may
      introduce age artifacts in the case of fine-grained samples. Both interference
      corrections and recoil displacements would be significantly reduced by
      irradiation with 2.45 MeV neutrons, which are produced by the deuteron-deuteron
      (D-D) fusion reaction 2H(d,n)3He. A new generation of D-D reactors should yield
      sufficiently high neutron fluxes (>10(12) n cm(-2)s(-1)) to be useful for
      40Ar/39Ar dating. Modeling indicates that irradiation with D-D neutrons would
      result in scientific benefits of improved accuracy and broader applicability to
      fine-grained materials. In addition, radiological safety would be improved, while
      both maintenance and operational costs would be reduced. Thus, development of
      high-flux D-D fusion reactors is a worthy goal for 40Ar/39Ar geochronology.

PMID- 15498682
TI  - Synthesis of a bis-(N-sec-butyl-dithiocarbamato)-nitrido-99mTc complex: a
      potential new radiopharmaceutical for brain perfusion studies.
AB  - A bis-(N-sec-butyl dithiocarbamato) nitrido technetium-99m complex
      [(99m)TcN(SBDTC)2] (SBDTC: N-sec-butyl dithiocarbamato) was synthesized by the
      reduction of (99m)TcO4(-) to [(99m)Tc[triple bond]N]2+ with stannous chloride in
      the presence of succinic dihydrazide and propylenediamine tetraacetic acid,
      followed by the addition of sodium N-sec-butyl dithiocarbamate dihydrate. The
      radiochemical purity of the complex was over 90% as measured by thin layer
      chromatography. It was stable over 6 h at room temperature. Its partition
      coefficient indicated that it was a good lipophilic complex. The electrophoresis
      results showed that the complex was neutral. Biodistribution studies in mice
      demonstrated that the complex accumulated in the brain with high uptake and good
      retention. The brain uptake (ID%/g) was 3.89, 3.44 and 2.82 and the brain/blood
      ratio was 1.41, 1.45, 1.00 at 5, 30 and 60 min post-injection respectively. These
      results suggested the potential usefulness of the complex as a brain perfusion
      imaging agent.

PMID- 15498683
TI  - Prosthetic radioiodination of interleukin-8 ([(123/131)I]-IL-8): biological
      behavior in a mouse infection model.
AB  - Numerous molecular entities with diverse structures have been radiolabeled and
      investigated as potential infection and inflammation detection agents. However,
      none of these molecules have gained the acceptance of gallium citrate or
      radiolabeled autologous white blood cells. We have radioiodinated interleukin-8
      using two different methods and tested the biological behavior of the products in
      mice. As expected, the direct radioiodinated material displayed extensive in vivo
      deiodination. The use of pyridine-based prosthetic label yielded a product with
      better kinetics than the direct radioiodination method and showed a better target
      to non-target ratio. Nonetheless, this method is not suited for labeling of
      bioactive peptides such as the title peptide because of the very high specific
      activity required to prevent cytotoxic effects in a human application.

PMID- 15498684
TI  - Tritium labelling of dopaminergic ligands domperidone and (+/-)-7-hydroxy DPAT.
AB  - Methods are presented for tritiating the D2 specific dopaminergic antagonist
      domperidone and D3 specific dopaminergic agonist (+/-)-7-hydroxy DPAT. Techniques
      to characterize the products of the tritiation are also given.

PMID- 15498685
TI  - Iodination and radiolabeling of alpha-allocryptopine with iodine-125.
AB  - A procedure for labeling of alpha-allocryptopine with 125I is reported in this
      article. Alpha-allocryptopine is first iodinated with largely excessive iodine
      monochloride, and then radiolabeled by isotopic exchange with Na125I in a
      dichloromethane-water two-phase system. The radiochemical purity and yield of the
      labeled product are typically as high as 94% and 72%, respectively. Further
      chromatographic purification gives a highly pure product (radiochemical purity >
      99%). The distribution of 125I-labeled alpha-allocryptopine in mice at 2 h after
      injection shows that the uptake of radioiodine in thyroid is negligibly low.

PMID- 15498686
TI  - Emission probabilities of K X- and gamma-rays following 51Cr and 67Ga decay.
AB  - Emission probabilities of K X- and gamma-rays following the decay of 51Cr and
      67Ga were precisely measured with a calibrated Si(Li) detector. The photopeak
      efficiency of the Si(Li) semiconductor detector was determined experimentally for
      about 4-400 keV energy range by using standard sources. Results of this study
      have been compared with the theoretical values and other available experimental
      results in the literature. Good agreement was observed between our results, and
      other available experimental results and theoretically calculated values.

PMID- 15498687
TI  - A study of neutron spectra from medical linear accelerators.
AB  - Medical accelerators with photon energies over 10 MeV generate an undesired fast
      neutron contamination in the therapeutic beam. In this work, the Monte Carlo code
      MCNP was used to simulate the transport of these photoneutrons across the head of
      various medical accelerators of high energy. The average and most probable
      neutron energies were obtained from these spectra, before and after crossing the
      accelerator shielding. The degradation of these spectra, when they cross concrete
      barriers with thickness which vary between 25 and 100 cm, was also studied.

PMID- 15498688
TI  - Activation cross-sections of long-lived products of proton-induced nuclear
      reactions on zinc.
AB  - In the frame of a systematic study of excitation functions induced by medium
      energy protons, the activation cross-sections on natural zinc were investigated
      for different applications. Excitation functions for production of 66,67Ga,
      62,65,69mZn, 64Cu, 57Ni, 55,56,57,58Co and 52,54Mn radioisotopes were measured by
      the stacked foil technique in the energy range of 26-67 MeV. Results were
      compared with the earlier reported experimental data and theoretical calculations
      based on the ALICE-IPPE code. Experimental data are presented for the first time
      for most of the products in the investigated energy range. Applications of the
      measured data for validating the cross-sections on highly enriched isotopic Zn
      targets and for thin layer activation method are discussed.

PMID- 15498690
TI  - Sorption of Cesium on smectite-rich clays from the Bohemian Massif (Czech
      Republic) and their mixtures with sand.
AB  - Sorption is an important process for the transport of radionuclides through
      backfill materials in a radioactive waste underground repository. Within this
      study, sorption of Cs on selected Czech clay materials and their mixtures with
      sand was investigated by batch tests. The experiments were performed under oxic
      conditions at 25 degrees C. Synthetic groundwater as a liquid phase and
      unconditioned clays (as they were provided by their producer) were used to reach
      the natural conditions as close as possible. Distribution ratios (Rds) of Cs for
      all selected clays rise with increase of the clay fraction in clay/sand mixtures
      in agreement with previous works studying sorption behaviour of such mixtures.
      The rise of Rds is from 10(2) cm3 g(-1) for mixtures with 80% of sand to 10(3)
      cm3 g(-1) for pure clays. There are significant differences between natural and
      technologically modified clays.

PMID- 15498689
TI  - On line gamma-ray spectrometry at open sea.
AB  - Set up and application of a stationary monitoring network for measuring specific
      gamma- activities in the Aegean Sea are described. Three NaI scintillator based
      spectrometers have been used to detect the gamma rays. The gross counting rate of
      each system was found to be nearly constant, when there was no rainfall. The
      volumetric activity of the natural gamma-ray emitter 40K in open sea varied from
      12,200 to 13,000 Bq/m3. The counting rate for 1461 keV 40K radiation was measured
      by intercalibration with an appropriate salinity sensor mounted close to the NaI
      detector system. A simple relation between the counting rate and the salt
      concentration has been observed. The amount of the artificial radioactivity from
      137Cs was increased up to seven times higher after strong rainfall, compared to
      the radiation level as given in literature (3.5-5.5 Bq/m3), while the 214Bi
      counting rate was increased up to ten times compared to the data without
      rainfall.

PMID- 15498691
TI  - Basic considerations for Monte Carlo calculations in soil.
AB  - Monte Carlo codes are extensively used for probabilistic simulations of various
      physical systems. These codes are widely used in calculations of neutron and
      gamma ray transport in soil for radiation shielding, soil activation by neutrons,
      well logging industry, and in simulations of complex nuclear gauges for in soil
      measurements. However, these calculations are complicated by the diversity of
      soils in which the proportions of solid, liquid and gas vary considerably
      together with extensive variations in soil elemental composition, morphology, and
      density. Nevertheless use of these codes requires knowledge of the elemental
      composition and density of the soil and its physical characteristics as input
      information for performing these calculations. It is shown that not always all of
      the soil parameters are critical but depend on the objectives of the
      calculations. An approach for identifying soil elemental composition and some
      simplifying assumptions for implementing the transport codes are presented.

PMID- 15498693
TI  - Water and solids mobility in foods.

PMID- 15498692
TI  - Using Cesium-137 technique to study the characteristics of different aspect of
      soil erosion in the Wind-water Erosion Crisscross Region on Loess Plateau of
      China.
AB  - The most serious soil erosion on Loess Plateau exists in the Wind-water Erosion
      Crisscross Region. In the past 20 years, the types and intensity of soil erosion
      and its temporal and spatial distribution were studied, but studies on the
      difference of soil erosion between slope aspects and slope positions in this area
      have no report. However, it is very important to analyze and evaluate
      quantitatively the characteristics of different aspects and positions of soil
      loss for the prevention and treatment of soil erosion in this area. The spatial
      pattern of net soil loss on 4 downslope transects in four aspects (east, west,
      south and north) on a typical Mao (round loess mound) in Liudaogou catchment in
      Wind-water Erosion Crisscross Region was measured in 2000 using the resident
      cesium-137 deficit technique. The purposes of this investigation were undertaken
      to determine whether or not 137Cs measurement would give a useful indication of
      the extent of soil loss and their characteristics from cultivated hillsides in
      different slope aspect and slope position in the study area. The results showed
      that the difference of soil erosion in different aspect was significant and the
      erosion rate was in this order: north > east > south > west. Compared with other
      areas, the difference of erosion rate between north hillside and south hillside
      was on the contrary, and the possible explanations could be the effect of wind
      erosion. Also, the percentage of wind erosion was estimated to be at least larger
      than 18% of total soil loss by comparing the difference of erosion amount in
      south hillside and north hillside. The erosion rates on different slope positions
      in all aspects were also different, the highest net soil loss occurred in the
      lower slope position, and the upper and middle slope positions were slight. The
      general trend of net soil loss on sloping surface was to increase in fluctuation
      with increasing downslope distance.

PMID- 15498694
TI  - Consumer reactions to food safety crises.

PMID- 15498695
TI  - An enzymatic process for corn wet milling.

PMID- 15498696
TI  - Present and future in process control and optimization of osmotic dehydration.
      From unit operation to innovative combined process: an overview.

PMID- 15498697
TI  - Insect management in food processing facilities.

PMID- 15498699
TI  - Clinical biomechanics of the peritalar joint.
AB  - The peritalar joint includes the articulations between the talus and calcaneus
      and the talus and navicular. Motion between the talus and calcaneus is described
      most often as rotation about an axis that points medially, anteriorly, and
      superiorly. This motion is considered to be triplanar, with inversion, plantar
      flexion, and adduction occurring together, whereas eversion, dorsiflexion, and
      abduction are associated. Similar motions have been described between the talus
      and navicular. Foot deformity, such as a pes planus or a pes cavus foot type, and
      hindfoot or midfoot joint fusion can alter the biomechanics of the peritalar
      joint.

PMID- 15498700
TI  - Imaging of the talus.
AB  - There are numerous options for imaging talar pathology. Of these, radiography,
      CT, scintigraphy, and MRI are used most commonly. Advantages and limitations of
      these techniques should be considered when formulating an imaging algorithm for
      evaluation of the patient's clinical problem.

PMID- 15498701
TI  - Surgical approaches to the talus.
AB  - Surgical approaches to the talus should allow access for fracture fixation,
      resection of osteophytes, treatment of osteochondral lesions, removal of painful
      os trigonum, and resection of hindfoot coalitions. This article describes the
      specific approaches to these conditions as well the structures at risk during
      surgery.

PMID- 15498702
TI  - Management of fractures of the talus: body and head regions.
AB  - Talar head and body injuries are not recognized easily and can create significant
      long-term disability when missed. Careful investigation of any injury about the
      ankle requires clinical and radiographic examination. A CT scan is extremely
      helpful in diagnosing and treating these injuries. Displaced fractures require
      open reduction of the major joint surfaces and internal fixation. Prolonged
      nonweight bearing and immobilization is the norm. Despite aggressive management,
      complications that involve avascular necrosis and posttraumatic arthritis to the
      subtalar and ankle joints occur frequently.

PMID- 15498703
TI  - Talar neck fractures.
AB  - Talus fractures are rare injuries that account for approximately 3% of all foot
      fractures; talar neck fractures account for almost 50% of all talus fractures.
      The appropriate diagnosis and treatment of these fractures play an important role
      in the patient's outcome. Treatment has evolved slowly throughout the years, from
      closed treatment to open reduction and internal fixation (ORIF). The treatment of
      type I and type II talar neck fractures is not uniform in the orthopedic
      community. The option of closed reduction versus ORIF is dependent upon the
      degree of injury, surgeon experience, and preference.

PMID- 15498704
TI  - Stage VI: massive osteochondral defects of the talus.
AB  - This article addresses very large osteochondral lesions of the talus with an
      osteonecrosis overlap. Six cases are discussed where lesions were deemed too
      large for osteochondral autograft transfer (OATS) or autologous chondrocyte
      transplant (ACT). These cases were treated with bulk fresh or fresh frozen
      matched talus allograft transplantation. The associated literature is reviewed.

PMID- 15498705
TI  - Osteonecrosis of the talus.
AB  - Talar osteonecrosis remains partially understood and a clinical challenge.
      Further research is necessary to elucidate the etiology, pathophysiology, and
      true incidence of this complex disorder fully. Optimal imaging strategies and
      staging systems also require further investigation. As our understanding of talar
      osteonecrosis evolves, so will our ability to treat this disorder promptly and
      properly.

PMID- 15498706
TI  - Avascular necrosis of the talus: current treatment options.
AB  - AVN of the talus is a challenging disease process with respect to patho
      physiology and treatment. We believe that our algorithm is a legitimate approach
      to aid the orthopedic surgeon in initiating a promising treatment. It is divided
      into different levels and allows to change between some. This is not the only way
      to proceed but it seems promising, especially if the long-term results with the
      vascularized bone grafts show revascularization of the talus. As always in
      medicine, the treatment needs to be individualized. Arthrodesis always should be
      the last option and is a challenging procedure.

PMID- 15498707
TI  - Use of talectomy in modern foot and ankle surgery.
AB  - Talectomy is a procedure that is undertaken rarely in modern orthopedic surgery;
      however, it has been performed for many years. Talectomy has been used most
      commonly in pediatric orthopedics with some degree of success in severe clubfoot
      deformity, arthrogryposis multiplex congenita, myelomeningocele, tuberculosis,
      and tumors. In adults, talectomy has been used in salvage procedures that involve
      nonunion of ankle fusions, failed total ankle arthroplasty, inflammatory
      arthropathy, neuroarthropathy, failed talar prostheses, failed pantalar fusions,
      adult neglected clubfoot, posttraumatic avascular necrosis talus, and deformities
      that are due to sciatic nerve palsy and compartment syndrome. This article
      consider what place talectomy has in modern adult foot and ankle surgery.

PMID- 15498708
TI  - Os trigonum.
AB  - There is a wide variation in the nomenclature for the posterior aspect of the
      talus (eg, os trigonum, trigonal process, Stieda process, posterior process).
      Injuries to these structures can be caused by chronic, repetitive impingement of
      the bony prominence or by acute hyperplantar flexion of the foot and ankle. After
      failing appropriate nonoperative treatment, surgical excision of the bony
      involvement is recommended. Surgical options include open or arthroscopic
      excision of the bony structure.

PMID- 15498710
TI  - Current indications for reduced-intensity allogeneic stem cell transplantation.
AB  - Stem cell transplantation preceded by reduced-intensity conditioning (RIC) is
      based on the use of immunosuppressive agents as the sine qua non to ensure donor
      cell engraftment. It is a curative option for select patients suffering from
      haematological and non-haematological malignancies. The most beneficial results
      are observed when a full donor engraftment is achieved with 'tolerable' graft-vs
      host disease (GVHD). To date, a vast amount of clinical data has been published,
      but in an uncontrolled manner. This review summarizes the currently known outcome
      of allogeneic transplants with RIC, with every disease category analysed
      separately. Unresolved problems include the optimal combination of
      immunosuppressive agents, the degree of infectious complications, and GVHD that
      may appear in some patients. Directions to overcome these complications are
      discussed. Despite the paucity of controlled clinical data, the current
      indications for RIC allogeneic transplantation are summarized based on the best
      available phase II data.

PMID- 15498711
TI  - Mesenchymal stem cells and haematopoietic stem cell transplantation.
AB  - The bone marrow serves as a reservoir for different classes of stem cells. In
      addition to haemopoietic stem cells, the bone marrow comprises a population of
      marrow stromal cells or mesenchymal stem cells (MSCs). These cells exhibit
      multilineage differentiation capacity, and are able to generate progenitors with
      restricted developmental potential, including fibroblasts, osteoblasts,
      adipocytes and chondrocyte progenitors. In addition, MSCs have been shown to
      possess immunosuppressive activity in vitro and in vivo. Clinical trials are
      underway to test whether MSCs are beneficial in patients undergoing allogeneic
      bone marrow transplantation. With the expanding role of stem cell transplants in
      different areas of medicine, including cardiology and orthopaedics, MSCs may
      become very important in the next few years.

PMID- 15498712
TI  - Cellular therapy of Epstein-Barr-virus-associated post-transplant
      lymphoproliferative disease.
AB  - During the immunodeficiency that follows hemopoietic stem cell transplant or
      solid organ transplant, lymphoproliferation can develop due to uncontrolled
      expansion of Epstein-Barr-virus (EBV)-infected B cells that express the full
      spectrum of EBV latent antigens. As development of post-transplant
      lymphoproliferative disease (PTLD) in these patients is clearly associated with a
      deficient EBV-specific cellular immune response, immunotherapy strategies to
      restore the EBV-specific immune response have been evaluated. In hemopoietic stem
      cell transplant recipients, adoptively transferred donor-derived EBV-specific T
      cells have been able to restore immunity and eradicate overt lymphoproliferation.
      Autologous or closely matched allogeneic EBV-specific cytotoxic T lymphocytes
      have also shown promise in recipients of solid organ transplant. The use of
      genetically modified T cells or newer suicide genes may result in improved safety
      and efficacy. Current challenges are to define indications for immunotherapy or
      antibody therapy in patients with incipient or overt PTLD.

PMID- 15498713
TI  - Minor histocompatibility antigens as targets of cellular immunotherapy in
      leukaemia.
AB  - Allogeneic human-leukocyte-antigen-matched stem cell transplantation is
      associated with a lower risk of relapse of leukaemia than autologous
      transplantation due to a T-cell-mediated graft-vs.-leukaemia effect. Replacement
      of patient haematopoiesis by donor haematopoiesis allows the application of donor
      derived specifically targeted cellular immunotherapy for the treatment of
      leukaemia. Following allogeneic transplantation, donor-derived T cells
      recognizing minor histocompatibility antigens expressed on haematopoietic cells
      from the patient may result in eradication of all haematopoietic cells of
      recipient origin. Since after transplantation, normal haematopoiesis is of donor
      origin, these T-cell responses may result in establishment of full donor
      chimerism associated with elimination of the haematological malignancy. By
      targeting the immune response to minor histocompatibility antigens that are not
      expressed on non-haematopoietic tissues, graft-vs.-host reactions may be limited.
      Several methods can be used for in vitro selection of T-cell responses with high
      specificity for malignant cells, and in vitro manipulation of donor T cells
      including transfer of antigen-specific T-cell receptors may greatly enhance
      specificity and efficacy of donor-derived cellular immunotherapy of
      haematological malignancies.

PMID- 15498714
TI  - Natural killer cells as a therapeutic tool in mismatched transplantation.
AB  - Natural-killer-cell-mediated, donor-vs-recipient alloresponses occur following
      transplantation of human-leukocyte-antigen (HLA)-haplotype-mismatched
      haematopoietic stem cells. Natural killer (NK) cell alloreactivity reduces the
      risk of relapse in acute myeloid leukaemia patients, while improving engraftment
      and protecting against graft-vs-host disease. NK cells are primed to kill by
      several activating receptors. NK cell killing of autologous cells is prevented as
      NK cells co-express inhibitory receptors (killer cell Ig-like receptors, KIR)
      that recognize groups of (self) major histocompatibility complex class I alleles.
      As KIRs are distributed clonally, the NK cell population in any individual
      constitutes a repertoire with different allospecificities. NK cells in the
      repertoire mediate alloreactions when the allogeneic targets do not express class
      I alleles that block them. High-resolution molecular HLA typing of recipient and
      donor, positive identification of donor KIR genes and, in some cases, functional
      assessment of donor NK clones will identify haplo-identical donors who are able
      to mount donor-vs-recipient NK alloreactions.

PMID- 15498715
TI  - In-vivo generation of leukaemia-derived dendritic cells.
AB  - Adoptive immunotherapy with transfusion of donor lymphocytes in allogeneic stem
      cell chimeras has been successful in the treatment of recurrent chronic
      myelogenous leukaemia (CML) and some patients with acute myeloid leukaemia (AML).
      The hypothesis that the graft-vs-leukaemia effect (GVL) is promoted by leukaemia
      derived dendritic cells has been supported by the concurrent treatment of
      patients with cytokines that are known to induce differentiation of leukaemia
      cells towards dendritic cells. In combination with donor lymphocyte transfusions,
      treatment with interferon-alpha and granulocyte-macrophage colony-stimulating
      factor has been studied in patients with recurrent CML and AML, and pre-emptively
      in patients with high-risk AML. Long-term remissions have been observed in
      cytokine-treated patients, indicating the beneficial effect of cytokine
      stimulation of GVL reactions. This is likely to be due to differentiation of
      leukaemia progenitor cells towards dendritic cells in vivo.

PMID- 15498716
TI  - Suicide gene therapy and the control of graft-vs-host disease.
AB  - Allogeneic bone marrow transplantation as a cure for leukaemia and lymphoma is
      limited by the development of graft-vs-host disease (GVHD), an immunological
      reaction of the donor's T lymphocytes against the host's normal tissues. One
      therapeutic option to treat GVHD is the transfer of 'suicide' genes into the
      donor's T lymphocytes to render them susceptible to prodrug administration. This
      procedure should permit the elimination of unwanted T lymphocytes in GVHD. The
      main genes proposed for such a strategy will be described in this chapter,
      together with the advantages and limitations found during preclinical and
      clinical studies to date.

PMID- 15498717
TI  - Potential use of CD40 ligand for immunotherapy of childhood B-cell precursor
      acute lymphoblastic leukaemia.
AB  - Around 20% of children affected by B-cell precursor acute lymphoblastic leukaemia
      (BCP-ALL) still experience a recurrence of the disease after diagnosis, despite a
      significant improvement in the cure rate (80%). Moreover, standard therapies have
      high and often unacceptable acute and chronic organ toxicity, with an increased
      risk for secondary malignancies. Therefore, new strategies are needed to improve
      overall survival and decrease treatment-associated morbidity. Recent in-vitro and
      in-vivo studies have demonstrated that CD40 engagement improves tumour
      immunogenicity and, consequently, generates a strong antitumour immune response.
      The CD40-CD40 ligand (CD40L) system is of pivotal importance in the immune
      response via interactions between T cells and antigen-presenting cells. The
      general aim of this chapter is to review the feasibility of developing cellular
      strategies to increase childhood BCP-ALL immunogenicity, and the potential use of
      CD40L as a new strategy to induce an antileukaemia immune response in BCP-ALL.

PMID- 15498718
TI  - Innovative approaches of adoptive immune cell therapy in paediatric recipients of
      haematopoietic stem cell transplantation.
AB  - Adoptive immune cell therapy represents one of the most promising fields of
      investigation in allogeneic haematopoietic stem cell transplantation (allo-HSCT).
      Preliminary studies indicate that adoptive immune cell therapy can be used to
      restore the immunocompetence of allo-HSCT recipients towards widespread pathogens
      in the early post-transplant period. These strategies can be of fundamental
      importance in patients given a T-cell-depleted allograft, a type of transplant
      that has been performed increasingly over the last few years. A few seminal
      studies have recently documented that prevention/treatment of Epstein-Barr-virus
      related lymphoproliferative disorders, human cytomegalovirus disease and invasive
      aspergillosis can be obtained through infusion of pathogen-specific T-cell lines
      or clones. Several efforts are also being directed towards the identification of
      strategies capable of selecting and/or strengthening specific graft-vs-leukaemia
      responses. In this regard, strategies of ex-vivo generation and expansion of
      clones or cell lines, specifically or preferentially leukaemia reactive, have
      been developed.

PMID- 15498719
TI  - Safety and efficacy in retrovirally modified haematopoietic cell therapy.
AB  - The enormous therapeutic potential of haematopoietic stem cells may be realized
      if we acquire the ability to control their survival in vitro and their behaviour
      in vivo. While extrinsic approaches using drugs are unlikely to be developed for
      this purpose in the near future, altering the intrinsic pool of biological
      information of stem cells by somatic gene transfer is more likely to succeed.
      Using the first generations of retroviral gene transfer vectors, we are
      confronted with the first examples of both successful therapeutic interventions
      and severe adverse events. The latter are related to the incomplete precision of
      the existing technologies. Concerted safety and efficiency evaluation has been
      enforced to further improve the prospects of this field. This review summarizes
      the current state of the debate, proposing future research directions towards
      understanding the complex interplay of risk factors related to random transgene
      insertion, unphysiological transgene expression and additional contributory
      factors of the specific therapeutic setting.

PMID- 15498720
TI  - Gene therapy for adenosine-deaminase-deficient severe combined immunodeficiency.
AB  - Adenosine-deaminase-deficient SCID was the first inherited disease to be treated
      with gene therapy. This life-threatening disorder is characterized by a purine
      defect that leads to impaired immune functions, recurrent infections and systemic
      metabolic abnormalities. The early gene therapy trials showed the safety and
      feasibility of engineering haematopoietic stem cells and peripheral blood
      lymphocytes using retroviral vectors. However, all patients were maintained on
      enzyme-replacement therapy, which prevented the evaluation of its efficacy and
      abolished the selective advantage for gene-corrected cells. It is only recently
      that the clinical efficacy of gene therapy has been investigated in the absence
      of enzyme-replacement therapy. Results of these studies showed that gene therapy
      with peripheral blood lymphocytes allowed correction of the T-cell defect, but
      provided insufficient systemic detoxification. Gene transfer in bone marrow stem
      cells, associated with non-myeloablative conditioning, allowed full immunological
      and metabolic correction of the adenosine-deaminase defect with clinical benefit.
      These results have important implications for future applications of gene therapy
      in other blood-borne disorders.

PMID- 15498721
TI  - Globin gene transfer for treatment of the beta-thalassemias and sickle cell
      disease.
AB  - The beta-thalassemias and sickle cell disease are severe congenital anemias that
      are caused by mutations that alter the production of the beta chain of
      hemoglobin. Allogeneic hematopoietic stem cell (HSC) transplantation is curative,
      but this therapeutic option is not available to the majority of patients. The
      transfer of a functional globin gene in autologous HCSs thus represents a highly
      attractive alternative treatment. This strategy, simple in principle, raises
      major challenges in terms of controlling the expression of the globin transgene,
      which ideally should be erythroid specific, differentiation-stage restricted,
      elevated, position independent, and sustained over time. Using lentiviral
      vectors, we have demonstrated that an optimised combination of proximal and
      distal transcriptional control elements permits lineage-specific, elevated
      expression of the beta-globin gene, resulting in therapeutic hemoglobin
      production and correction of anemia in beta-thalassemic mice. Several groups have
      now confirmed and extended these findings in various mouse models of severe
      hemoglobinopathies, thus generating enthusiasm for a genetic treatment based on
      globin gene transfer. Furthermore, globin vectors represent a general paradigm
      for the regulation of transgene function and the improvement of vector safety by
      restricting transgene expression to the differentiated progeny within a single
      lineage, thereby reducing the risk of activating oncogenes in hematopoietic
      progenitors. Here we review the principles underlying the genesis of regulated
      vectors for stem cell therapy.

PMID- 15498722
TI  - A case study of primiparous maternal and infant gorilla (Gorilla gorilla gorilla)
      behavior.
AB  - A primiparous mother and her infant were subjects of a longitudinal behavioral
      study at Lincoln Park Zoo in Chicago, Illinois. From November 1998 to November
      1999, we collected a total of 100 hr of focal nonhuman animal instantaneous point
      sampling and all occurrence data on the mother and her infant. After 8 months, we
      introduced the 4-member focal group to an 8-member gorilla group, thus providing
      an opportunity to study the effect of the introduction on mother-infant behavior.
      Overall, time the pair spent physically apart was notably high with contact and
      proximate scores steadily decreasing over time. The infant was largely
      responsible for maintaining social proximity, rarely leaving the mother and
      frequently approaching her. In contrast, the mother left the infant frequently
      and approached the infant minimally. Maternal affiliative and nonaffiliative
      behaviors fluctuated throughout the study. Over time, both decreased. Despite a
      precarious maternal relationship, infant developmental trends were typical for
      captive gorillas. The results of this study suggest that allowing flexibility in
      judging maternal conduct can be of benefit to successful gorilla husbandry.

PMID- 15498723
TI  - A two-choice preference assessment with five cotton-top tamarins (Saguinus
      oedipus).
AB  - A study selected 5 cotton-top tamarins (Saguinus oedipus) located at the Frank
      Buck Zoo in Gainesville, Texas, for a food preference assessment. The study used
      a paired-choice procedure across 7 different food items for all 5 tamarins.
      Preferences for the food items across all the tamarins varied, although general
      trends were noted as well. This article discusses the benefits of using paired
      choice preference assessments in zoo settings.

PMID- 15498725
TI  - Disposition of shelter companion animals from nonhuman animal control officers,
      citizen finders, and relinquished by caregivers.
AB  - Many private not-for-profit humane societies have contracts with their local
      government entities to provide nonhuman animal control services that the law
      commonly requires the government to provide to its residents. These services
      normally have the humane organization providing either the total animal control
      program (including field work to pick up stray animal companions, enforcing local
      animal ordinances, and the impounding of stray companion animals) or just the
      boarding of companion animals with no fieldwork or enforcement duties. Shelter
      companion animals normally come from three main sources: (a) stray or lost
      companion animals impounded by animal control field officers or animals impounded
      for violations of humane care regulations; (b) stray companion animals brought to
      the shelter by a resident who happens across, and catches, a lost companion
      animal and delivers the animal to the shelter; and (c) companion animals
      relinquished by their caregivers.

PMID- 15498724
TI  - The effect of environmental manipulation on behavior, salivary cortisol, and
      growth of piglets weaned at 14 days of age.
AB  - Environmental enrichment can be a useful tool to reduce belly nosing behaviors in
      early weaned piglets. The aim of this study was to assess the effect of
      environmental enrichment on behavior, salivary cortisol, and productivity of
      piglets weaned at 14 days of age. The study assigned 112 piglets (line Camborough
      22 of PIC) into 2 treatments, control and enriched, and observed them for 192 hr
      in 3 periods: 14 to 28 days of age (Phase 1), 28 to 42 days of age (Phase 2), and
      42 to 54 days of age (Phase 3). The study obtained saliva samples in each phase
      from 56 piglets selected randomly from each group for cortisol determination.
      Comparisons between both treatments and phases included the following: proportion
      of time belly nosing, latency of approaching a person, average levels of salivary
      cortisol, and daily weight gain. Belly nosing was higher and latency of
      approaching a person lower in the control group than in the enriched one (p < .05
      and p < .01). Belly nosing was lower in Phase 3 (p < .05); latency of approaching
      a person was higher in Phase 1 with respect to Phase 2, and this was higher with
      respect to Phase 3 (p < .01). There were no differences in salivary cortisol
      levels between treatments or phases. Weight gain was higher in the enriched group
      (p < .001). Environmental enrichment in piglets weaned at 14 days of age resulted
      in a reduced proportion of time nosing, reduced latency of response to humans,
      and better growth than piglets in barren environments.

PMID- 15498726
TI  - Ethics and welfare in southeast Asian zoos.

PMID- 15498727
TI  - The use of dogs in medical and veterinary training: understanding and approaching
      student uneasiness.

PMID- 15498728
TI  - Levels of citation of nonhuman animal studies conducted at a Canadian research
      hospital.
AB  - The publication of scientific articles that receive few or no citations raises
      questions of the appropriate use of resources as well as ethics. In the case of
      animal research, the ethics issue extends beyond human patients to nonhuman
      animals, as the research subjects them to pain and, typically, to death. This
      study is a citation analysis of animal research conducted at Toronto's Hospital
      for Sick Children (HSC). Of the 594 publications (1990 to 1995) on animal
      research by affiliates of HSC, 29% received fewer than 10 citations in a 10-year
      period. We compare the research history of 13 "best" and 13 "worst" HSC
      scientists. Worst researchers continue to do infrequently cited research.
      Recommendations indicate how institutions and researchers can become more
      effective and accountable.

PMID- 15498729
TI  - Distribution of nonhuman animal versus nonanimal research funding at four U.S.
      institutions in fiscal year 2000.

PMID- 15498733
TI  - The effects of the fast track program on serious problem outcomes at the end of
      elementary school.
AB  - This study examines the effects of the Fast Track program, which is a
      multicomponent, intensive intervention for children with early-onset conduct
      problems and continues from 1st grade through high school. Prior research has
      shown that Fast Track produces small positive effect sizes on children's social
      and behavioral outcomes at the end of 1st and 3rd grades in comparison to control
      children. This study addresses the important question of whether this
      intervention reduces cases of serious problems that can occur during the 4th- and
      5th-grade years. Fast Track did have a significant but modest influence on
      children's rates of social competence and social cognition problems, problems
      with involvement with deviant peers, and conduct problems in the home and
      community, compared to children in the control condition. There was no evidence
      of intervention impact on children's serious problems in the school setting at
      Grades 4 and 5. This evaluation indicates that Fast Track has continued to
      influence certain key areas of children's adjustment throughout the elementary
      school years, reducing children's likelihood of emerging as cases with problems
      in their social, peer, or home functioning. The stage is set to examine potential
      prevention effects on these youths' serious antisocial behaviors during
      adolescence.

PMID- 15498734
TI  - A three-generational study of transmission of risk for sexual abuse.
AB  - This intergenerational study investigates histories of both attachment
      relationships and abusive experiences and domains of current functioning that
      distinguish families of sexually abused children from families of nonabused
      children. The participants included (a) 199 nonoffending African American mothers
      of whom approximately half had children with documented sexual abuse histories
      and half had children with no documented abuse histories and (b) 106 maternal
      grandmothers of these children; approximately half had sexually abused
      grandchildren and half had grandchildren with no documented abuse. The children
      were 4 to 12 years old. Histories of abuse and attachment experiences and current
      functioning of the grandmother and mother were evaluated. Logistic regression
      analyses revealed that sexual abuse in a child was best predicted by 3 factors:
      maternal problems in adult functioning, a currently negative relationship between
      the grandmother and mother, and a disrupted pattern of caregiving during the
      mother's childhood. The findings underscore that troubled intergenerational
      attachment relationships in families can significantly heighten the risk of a
      child being sexually abused.

PMID- 15498735
TI  - Resilience in parentally bereaved children and adolescents seeking preventive
      services.
AB  - This study examined environmental stress, family, and child variables that
      differentiate resilient children and adolescents from those with mental health
      problems following the death of a primary caregiver. The community-based sample
      included 179 bereaved children ages 8 to 16 years and their surviving caregivers
      who completed a test battery of measures before participating in a prevention
      program. Forty-four percent of bereaved children were classified as resilient and
      56% as affected based on the absence of clinically significant mental health
      problems on at least 1 measure as reported by either the child, surviving
      caregiver, or teacher on standardized measures of mental health problems. Results
      of multivariate analyses indicated that bereaved resilient versus affected status
      was a function of both family and child variables. Higher levels of caregiver
      warmth and discipline and lower levels of caregiver mental health problems were
      family-level variables that significantly differentiated resilient children from
      affected children. Bereaved children's perceptions of less threat in response to
      negative events and greater personal efficacy in coping with stress were child
      level variables that differentiated resilient from affected status. Family and
      child variables were entered into a discriminant function analysis that correctly
      classified 72% of the sample. The findings are consistent with a model of
      resilience in which multilevel variables account for children's positive
      adaptation following exposure to adversity.

PMID- 15498736
TI  - Direct and indirect effects of parenting and children's goals on child
      aggression.
AB  - This study tested a dual-mediation model of the relations among harsh parenting,
      hostile social information processing, and level of child aggression in a sample
      of 239 (150 male, 89 female) 2nd- to 4th-grade children. The theoretical model
      posited that harsh parenting has both direct and indirect effects on child level
      of aggression, with the indirect effects mediated through children's social
      goals. The model further posited that the impact of social goals on aggression is
      mediated through other social cognitive processes (i.e., attributions of hostile
      intent, hostile solution generation, and positive outcome expectancies for
      aggression). We tested the dual-mediation model with structural equation modeling
      and found it to be a good fit to the data. Results were consistent with the view
      that parenting affects children's goal orientation and that children's goal
      orientation affects their behavior via online processing in social situations.

PMID- 15498737
TI  - A prospective study of the consequences of marital disruption for adolescents:
      predisruption family dynamics and postdisruption adolescent adjustment.
AB  - This study employed data from the National Longitudinal Study of Adolescent
      Health to examine the consequences of marital disruption for youth prospectively.
      Using a diverse sample of 6,416 youth, we examined pre- and postdisruption group
      differences among youth in subsequently disrupting and continuously intact homes.
      We also examined the extent to which predisruption family dynamics (e.g., marital
      discord) accounted for both pre- and postdisruption group differences in youth
      functioning and examined the interaction between level of marital discord and
      marital disruption. Group differences in adjustment emerged at both time-points
      and were better explained by family-level variables than by marital disruption.
      Further, level of marital discord interacted with marital disruption, predicting
      differential youth outcomes. The implications of these findings for understanding
      and explaining the heterogeneity of divorce outcomes are discussed.

PMID- 15498738
TI  - Severity of adolescent delinquency among boys with and without attention deficit
      hyperactivity disorder: predictions from early antisocial behavior and peer
      status.
AB  - This study evaluated predictors of adolescent delinquency severity (11 to 17
      years of age) among a diverse group of preadolescent boys with attention deficit
      hyperactivity disorder (ADHD; n=100) and age-matched comparison boys (n=75).
      During childhood, baseline assessments yielded diagnostic information, and
      naturalistic summer programs provided multimethod measures of overt aggression,
      covert antisocial behavior (ASB), and peer status. Five years later, multi
      informant measures of ASB and delinquency were gathered and independently rated.
      Baseline ADHD, overt aggression, and peer status were not significantly related
      to adolescent delinquency severity. Observed noncompliance and an objective
      measure of covert ASB each independently predicted delinquency. Covert ASB
      predicted delinquency severity more strongly for comparison boys than for
      probands.

PMID- 15498739
TI  - Anxiety- and depression-related thoughts in children: development and evaluation
      of a cognition measure.
AB  - This study examined anxiety- and depression-related cognitive content in
      children. We developed the Children's Thought Questionnaire (CTQ) to include
      anxious thoughts characterized by threat and uncertainty; depressive thoughts by
      loss, self-deprecation, and certainty/hopelessness; and positive thoughts by
      interest, pleasure, and positive self-reference. The CTQ and measures of anxious
      and depressive symptoms were completed by 193 5th- and 6th-grade children.
      Exploratory factor analysis of the CTQ revealed that items loaded on 2 factors
      according to negative and positive valence. However, use of conceptually derived
      subscales demonstrated specificity, with higher levels of anxious thoughts
      uniquely predicting greater anxious symptoms and higher depressive thoughts
      uniquely predicting greater depressive symptoms. Furthermore, positive thoughts
      were negatively related to depressive symptoms but either unrelated or positively
      related to anxious symptoms, thus providing support for cognitive specificity.

PMID- 15498740
TI  - Psychopathy in youth and intelligence: an investigation of Cleckley's hypothesis.
AB  - Cleckley (1941) hypothesized that true or "primary" psychopathic individuals have
      "good" intelligence. This study examined the relation between psychopathy and
      intelligence in 122 detained children and adolescents. We used the Psychopathy
      Checklist-Youth Version (PCL-YV; Forth, Kosson, & Hare, 2003) to assess
      psychopathy and administered novel intelligence measures to tap diverse
      interpretations of the intelligence construct (e.g., traditional and triarchic
      intelligence). Structural equation modeling indicated that dimensions of
      psychopathy and intelligence were related in unique and important ways. In
      particular, psychopathy traits reflecting a superficial and deceitful
      interpersonal style were positively related to intellectual skills in the verbal
      realm (Kaufman's Brief Intelligence Test [K-BIT]; Kaufman & Kaufman, 1990) and a
      nontraditional intellectual measure reflecting creativity, practicality, and
      analytic thinking as measured by Sternberg's Triarchic Abilities Test (STAT;
      Sternberg, 1993). Finally, the results also suggested that psychopathy traits
      reflecting disturbances in affective processing were inversely associated with
      verbal intellectual abilities. Thus, Cleckley's hypothesis was partially
      supported by the data, when taking into account the facets of psychopathy and
      when examining intelligence from the perspective of traditional and more novel
      and contemporary intellectual models.

PMID- 15498741
TI  - Cognitive predictors of obsessive-compulsive symptoms in adolescence: a
      preliminary investigation.
AB  - This study examined relations among responsibility attitudes, metacognitive
      beliefs, and obsessive-compulsive (O-C) symptoms in youth. One hundred sixty-six
      nonclinical youth (ages 13 to 17 years) completed the following: Responsibility
      Attitude Scale (RAS; Salkovskis et al., 2000); Meta-Cognitions Questionnaire
      Adolescent Version (MCQ-A; Cartwright-Hatton et al., 2004); Children's Depression
      Inventory-Short Form (CDI-S; Kovacs, 1985); Revised Children's Manifest Anxiety
      Scale (RCMAS; Reynolds & Richmond, 1978); the Leyton Obsessional Inventory-Child
      Version Survey Form (LOI-CVS; Berg, Whitaker, Davies, Flament, & Rapoport, 1988).
      Participants endorsed a range of responsibility and metacognitive beliefs, and
      both responsibility and metacognition were positively correlated with O-C
      symptoms. However, when age, sex, and depression were controlled, only
      metacognition was a predictor of O-C symptoms. The findings suggest metacognition
      and responsibility may be important correlates of O-C symptoms in youth.

PMID- 15498742
TI  - Emotion regulation in children with anxiety disorders.
AB  - This study examined emotion management skills in addition to the role of
      emotional intensity and self-efficacy in emotion regulation in 26 children with
      anxiety disorders (ADs) ages 8 to 12 years and their counterparts without any
      form of psychopathology. Children completed the Children's Emotion Management
      Scales (CEMS) and Emotion Regulation Interview (ERI), and mothers reported on
      their children's emotion regulation using the Emotion Regulation Checklist (ERC).
      Results indicated that children who met Diagnostic and Statistical Manual for
      Mental Disorders (4th ed., American Psychiatric Association, 1994) criteria for
      an anxiety disorder had difficulty managing worried, sad, and anger experiences,
      potentially due to their report of experiencing emotions with high intensity and
      having little confidence in their ability to regulate this arousal. These
      findings indicate that emotion regulation needs to be considered centrally in
      research with anxious populations.

PMID- 15498743
TI  - Emotion awareness and identification skills in adolescent girls with bulimia
      nervosa.
AB  - This study examined emotion-identification skills in 19 adolescent girls (M
      age=16 years, 8 months) diagnosed with a Diagnostic and Statistical Manual of
      Mental Disorders (4th ed. [DSM-IV], American Psychiatric Association, 1994)
      diagnosis of bulimia nervosa or eating disorder not otherwise specified in the
      bulimic spectrum, 19 age-matched girls with a DSM-IV diagnosis of unipolar
      depression, and 19 age-matched girls without a mental health history. Findings
      revealed that girls with bulimia nervosa compared to girls in the depressed and
      community control groups endorsed significantly greater reluctance to express
      emotions and inferior interoceptive awareness. Moreover, they exhibited
      significantly longer latencies to retrieve information regarding their emotional
      state in self-generated situations. When provided with a list of emotion labels,
      girls with bulimia endorsed significantly more labels to describe their responses
      to typical adolescent situations than girls in the control groups.

PMID- 15498744
TI  - The relation between disinhibition and emotion regulation in boys with attention
      deficit hyperactivity disorder.
AB  - This study examined group differences of 49 boys ages 6 to 11 years with and
      without attention deficit hyperactivity disorder (ADHD) in emotion regulation
      during frustrating peer competition. Half of all boys in each group were
      explicitly instructed to hide their feelings if they became upset during the
      competition. Behavioral inhibition, both before and after the competitive task,
      was examined using the Stop Signal Task (SST), and emotion regulation was
      assessed via structured observation data. Effect sizes indicated that impulsive
      ADHD boys displayed greater disinhibition and were less effective at emotion
      regulation than comparison boys. In addition, boys with ADHD were unsuccessful in
      masking their emotions even when instructed to do so. In contrast, comparison
      boys were more successful at emotion regulation when given instruction to self
      regulate, and these regulatory attempts predicted later inhibitory control.
      Findings are discussed in the context of current ADHD-related theories of
      inhibitory deficit, and suggestions for future research are provided.

PMID- 15498745
TI  - Behavioral inhibition sensitivity and emotional response suppression: a
      laboratory test among adolescents in a fear-relevant paradigm.
AB  - This study examined behavioral inhibition sensitivity and emotional suppression
      in a fear-relevant slide-viewing paradigm among adolescents (n=95). After
      controlling for state anxiety, behavioral inhibition sensitivity significantly
      predicted subjective anxiety and the valence and control dimensions of emotional
      responding but was not associated with arousal-based indexes of distress.
      Contrary to prediction, emotional suppression did not affect emotional or
      psychophysiological responsiveness. These results are discussed in relation to
      vulnerability to anxiety-related distress among adolescents.

PMID- 15498746
TI  - Expressive writing intervention for adolescents' somatic symptoms and mood.
AB  - The effects of a widely used expressive writing intervention on adolescents'
      somatic symptoms, distress, and positive psychological functioning were
      evaluated. Eighth-grade (n=106) students were randomly assigned to write about
      either an emotional or a neutral topic for 3 consecutive days. Students completed
      measures of somatic symptoms, medical visits, distress, and positive functioning
      at baseline, postintervention, and 2 and 6 weeks later. Somatic symptoms and
      medical visits were unchanged as a result of the intervention. However,
      significant Time Condition effects indicated that optimism scores increased,
      negative-affect scores decreased, and positive-affect words in student essays
      increased in the experimental condition. Expressive writing shows promise as a
      cost-efficient intervention to address the emotional concerns of young
      adolescents; further work with clinical populations may lead to even more robust
      results.

PMID- 15498747
TI  - Internalizing behaviors among kindergarten children: measuring dimensions of
      social withdrawal with a checklist.
AB  - Three studies examined whether different types of withdrawal among young children
      could be assessed with a short checklist. In Study 1, kindergarten teachers rated
      487 children on a modified version of the Behavior Questionnaire for Two- to Six
      Year-Olds (BQTSYO). Exploratory factor analyses yielded 2 withdrawal factors,
      Social Inhibition and Solitary Behavior, and a factor of Emotional Dysregulation.
      In Study 2, an adjusted version of the checklist was completed for 858
      kindergartners. The 3 factors of Social Inhibition, Solitary Behavior, and
      Emotional Dysregulation were identified in one half of the sample and confirmed
      in the other. They could be measured with 3 internally consistent scales. No
      gender differences were found on the scales. Their content validity was supported
      by unique associations with teachers' free descriptions of children's behaviors
      in Study 3. Results suggest that the instrument is adequate for the assessment of
      different types of withdrawal.

PMID- 15498748
TI  - Parent-rated externalizing behavior in preschoolers: the predictive utility of
      structured interviews, teacher reports, and classroom observations.
AB  - This study investigated multiple forms of home and school assessment as
      predictors of parent-rated behavior problems across a preschool year.
      Participants were a community sample of 79 preschool children, their parents, and
      their teachers. Parent ratings of behavior problems were obtained toward the
      beginning of the school year and approximately 6 months later. Behavior problems
      were also assessed early in the school year using parent structured interviews,
      teacher-rating scales, and classroom observations of problem and prosocial
      behavior. Consistent with hypotheses, each assessment method significantly
      predicted year-end parent ratings of behavior problems, even above initial
      ratings.

PMID- 15498749
TI  - Treatment of childhood traumatic grief.
AB  - Childhood traumatic grief (CTG) is a condition in which trauma symptoms impinge
      on children's ability to negotiate the normal grieving process. Clinical
      characteristics of CTG and their implications for treatment are discussed, and
      data from a small number of open-treatment studies of traumatically bereaved
      children are reviewed. An empirically derived treatment model for CTG is
      described; this model addresses both trauma and grief symptoms and includes a
      parental treatment component. Future research directions are also addressed.

PMID- 15498750
TI  - Informed consent and clinical research involving children and adolescents:
      implications of the revised APA ethics code and HIPAA.
AB  - In 2003, 2 new sets of rules and regulations affecting the conduct of clinical
      research involving children and adolescents went into effect: the revised
      American Psychological Association's (APA) Ethical Principles of Psychologists
      and Code of Conduct (APA, 2002; effective June 1, 2003) and the Privacy Rule (45
      CFR Part 160 and A and E of Part 164; effective April; 14, 2003) of the Health
      Insurance Portability and Accountability Act (HIPAA: Public Law 104-191). This
      article highlights those APA ethical standards and HIPAA regulations relevant to
      clinical research involving children and adolescents and discusses how
      psychologists can apply these rules in ways that will ensure ethical and legal
      compliance.

PMID- 15498753
TI  - Hypertension in diabetes: is there a place for age-adjusted centile cut-offs in
      those aged <50 years?
AB  - BACKGROUND: Conventional cut-offs for hypertension are arbitrary, and vascular
      complications can occur below these values, particularly in diabetes. AIM: To
      evaluate systolic blood pressure (SBP) distribution in diabetes and control
      populations, comparing hypertension prevalence using either conventional cut-offs
      (140 and 160 mmHg) or age-adjusted centile (75(th) and 90(th)) cut-offs derived
      from the control population. METHODS: We compared 2521 individuals with diabetes
      to 5809 controls, after excluding those on anti-hypertensives and with
      established vascular disease in both groups. RESULTS: Diabetic individuals were
      older (mean +/- SD 56 +/- 16 vs. 43 +/- 16years, diabetes vs. controls), and had
      higher BMI (29 +/- 5 vs. 24 +/- 4 kg /cm(2)) and SBP (145 +/- 23 vs. 131 +/- 18
      mmHg, all p < 0.001). These factors were adjusted for in subsequent analysis. SBP
      rose with age and was also significantly higher in the diabetes group. In
      diabetes, conventional cut-offs indicated less hypertension in those aged < 50
      years, compared to age-adjusted centile cut-offs. In age bands 18-29, 30-39, 40
      49, 50-59, 60-69 and >70 years of the diabetes group, 24%, 33%, 43%, 62%, 70% and
      74%, respectively exceeded 140 mmHg, compared to 35%, 44%, 43%, 45%, 40% and 27%
      exceeding the control-derived 75(th) centile value. DISCUSSION: The use of
      control-derived age-adjusted cut-offs may provide an alternative approach to
      define hypertension in diabetes that may be of particular relevance to younger
      patients, although this would require validation against outcomes.

PMID- 15498754
TI  - Wilting weed?Arabidopsis might provide new insights into workings of protein
      linked to a premature aging disease.

PMID- 15498755
TI  - Sticky situation.DNA landing sites for worm hibernation protein might flag aging
      associated genes.

PMID- 15498756
TI  - Gone to waste.Inflammation-producing compound spurs muscle deterioration.

PMID- 15498757
TI  - Aging-related research in the "-omics" age.
AB  - The application of high-throughput technologies to aging-related research has the
      potential to dramatically enhance our understanding of how longevity is
      determined at a molecular level. Genome-scale studies are being carried out in
      every major model system used for aging-related research, and new technologies
      are being developed to rapidly identify mutations or small-molecules that
      increase life span. A meta-analysis of data derived from genome-wide studies of
      aging in simple eukaryotes will allow the identification of conserved
      determinants of longevity that can be tested in mammals.

PMID- 15498758
TI  - Microarrays as a tool to investigate the biology of aging: a retrospective and a
      look to the future.
AB  - The use of microarrays as a tool to investigate fundamental biological questions
      has become ubiquitous over the past several years. Microarrays are becoming as
      common as the polymerase chain reaction or any of the other tools in the
      molecular biologist's armory. Unlike experiments involving other tools, however,
      the design and analysis of microarray experiments present some unique problems to
      molecular biologists, problems with which statisticians have long been familiar.
      In this overview of microarrays and aging-related research, we will review
      selected highlights of microarray studies that have been carried out to study
      aging to date, as well as discuss some of the potential problems that routinely
      arise during these types of experiments, especially in the context of aging.

PMID- 15498759
TI  - Surfactant protein A binds Mycoplasma pneumoniae with high affinity and
      attenuates its growth by recognition of disaturated phosphatidylglycerols.
AB  - Surfactant Protein A (SP-A) is an abundant, multifunctional lectin that resides
      within the bronchoalveolar compartment of the lung and plays an important role in
      the innate immunity of the organ. Mycoplasma pneumoniae is a human pathogen that
      resides in the same compartment as SP-A, and we examined the interaction between
      the two. Preparations of human and rat SP-A recognized the mycoplasma with high
      affinity in the presence of Ca(2+), exhibiting apparent K(')(d) values in the
      nanomolar range. Membranes prepared from the microbe also bound human and rat SP
      A with similar characteristics and affinity to the intact cells. The ligand for
      SP-A was insensitive to proteolysis. Lipid extracts prepared from the mycoplasma,
      bound SP-A with high affinity when examined by ligand blot analysis. These lipid
      extracts were also potent competitive inhibitors (IC(50) = 0.2 nM) of human SP-A
      binding to mycoplasma membranes. The major lipid ligands for the protein
      identified by mass spectrometry are a group of disaturated phosphatidylglycerols.
      The addition of SP-A to cultures of M. pneumoniae markedly attenuated the growth
      of the organism assessed by colony formation, metabolic activity, and DNA
      replication. The bacteriostatic effects of SP-A were reversed by
      dipalmitoylphosphatidylglycerol. These findings demonstrate that human SP-A can
      play a direct role in antibody-independent immunity to M. pneumoniae by
      interacting with lipid ligands expressed on the surface of the organism and
      implicate SP-A in the immediate host response to the bacteria.

PMID- 15498760
TI  - The yeast mitochondrial citrate transport protein: characterization of
      transmembrane domain III residue involvement in substrate translocation.
AB  - Previous examination of the accessibility of a panel of single-Cys mutants in
      transmembrane domain III (TMDIII) of the yeast mitochondrial citrate transport
      protein to hydrophilic, cysteine-specific methanethiosulfonate reagents, enabled
      identification of the water-accessible surface of this domain and suggested its
      potential participation in the formation of a portion of the substrate
      translocation pathway. To evaluate this idea, we conducted a detailed
      characterization of the functional properties of 20 TMDIII single-Cys
      substitution mutants. Kinetic studies indicate that the A118C, S123C, and K134C
      mutants displayed a 3- to 7-fold increase in K(m). Moreover, the A118C mutation
      caused a doubling of the V(max) value, whereas the S123C, E131C, and K134C
      mutations caused V(max) to dramatically decrease, resulting in a reduction of the
      catalytic efficiencies of these three mutants by >97%. Examination of the ability
      of citrate to protect against the inhibition mediated by sodium (2
      sulfonatoethyl)methanethiosulfonate (MTSES) indicated that citrate conferred
      significant protection of cysteines substituted at eight water-accessible
      locations (i.e. Gly-115, Leu-116, Gly-117, Leu-121, Ser-123, Val-127, Glu-131,
      and Thr-135), but not at other sites. Importantly, similar levels of protection
      were observed at both 4 degrees C and 20 degrees C. The temperature independence
      of the protection indicates that substrate binding and/or occupancy of the
      transport pathway sterically blocks the access of MTSES to these sites, thereby
      providing direct protection, without involvement of a major protein
      conformational change. The significance of these extensive functional
      investigations is discussed in terms of the three-dimensional CTP homology model
      that we previously developed and a new model of the dimer interface.

PMID- 15498761
TI  - A homolog of Albino3/OxaI is essential for thylakoid biogenesis in the
      cyanobacterium Synechocystis sp. PCC6803.
AB  - YidC/OxaI play essential roles in the insertion of a wide range of membrane
      proteins in Eschericha coli and mitochondria, respectively. In contrast, the
      chloroplast thylakoid homolog Albino3 (Alb3) facilitates the insertion of only a
      specialized subset of proteins, and the vast majority insert into thylakoids by a
      pathway that is so far unique to chloroplasts. In this study, we have analyzed
      the role of Alb3 in the cyanobacterium Synechocystis sp. PCC6803, which contains
      internal thylakoids that are similar in some respects to those of chloroplasts.
      The single alb3 gene (slr1471) was disrupted by the introduction of an antibiotic
      cassette, and photoautotrophic growth resulted in the generation of a merodiploid
      species (but not full segregation), indicating an essential role for Alb3 in
      maintaining the photosynthetic apparatus. Thylakoid organization is lost under
      these conditions, and the levels of photosynthetic pigments fall to approximately
      40% of wild-type levels. Photosynthetic electron transport and oxygen evolution
      are reduced by a similar extent. Growth on glucose relieves the selective
      pressure to maintain photosynthetic competence, and under these conditions, the
      cells become completely bleached, again indicating that Alb3 is essential for
      thylakoid biogenesis. Full segregation could not be achieved under any growth
      regime, strongly suggesting that the slr1471 open reading frame is essential for
      cell viability.

PMID- 15498762
TI  - Controlling the regiospecific oxidation of aromatics via active site engineering
      of toluene para-monooxygenase of Ralstonia pickettii PKO1.
AB  - A primary goal of protein engineering is to control catalytic activity. Here we
      show that through mutagenesis of three active site residues, the catalytic
      activity of a multicomponent monooxygenase is altered so that it hydroxylates all
      three positions of toluene as well as both positions of naphthalene. Hence, for
      the first time, an enzyme has been engineered so that its regiospecific oxidation
      of a substrate can be controlled. Through the A107G mutation in the alpha-subunit
      of toluene para-monooxygenase, a variant was formed that hydroxylated toluene
      primarily at the ortho-position while converting naphthalene to 1-naphthol.
      Conversely, the A107T variant produced >98% p-cresol and p-nitrophenol from
      toluene and nitrobenzene, respectively, as well as produced 2-naphthol from
      naphthalene. The mutation I100S/G103S produced a toluene para-monooxygenase
      variant that formed 75% m-cresol from toluene and 100% m-nitrophenol from
      nitrobenzene; thus, for the first time a true meta-hydroxylating toluene
      monooxygenase was created.

PMID- 15498763
TI  - Characterization of ligand binding to the bifunctional key enzyme in the sialic
      acid biosynthesis by NMR: II. Investigation of the ManNAc kinase functionality.
AB  - N-Acetylmannosamine (ManNAc) is the physiological precursors to all sialic acids
      that occur in nature. As variations in the sialic acid decoration of cell
      surfaces can profoundly affect cell-cell, pathogen-cell, or drug-cell
      interactions, the enzymes that convert ManNAc into sialic acid are attractive
      targets for the development of drugs that specifically interrupt sialic acid
      biosynthesis or lead to modified sialic acids on the surface of cells. The first
      step in the enzymatic conversion of ManNAc into sialic acid is phosphorylation,
      yielding N-acetylmannosamine-6-phosphate. The enzyme that catalyzes this
      conversion is the N-acetylmannosamine kinase (ManNAc kinase) as part of the
      bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine
      kinase. Here, we employed saturation transfer difference (STD) NMR experiments to
      study the binding of ManNAc and related ligands to the ManNAc kinase. It is shown
      that the configuration of C1 and C4 of ManNAc is crucial for binding to the
      enzyme, whereas the C2 position not only accepts variations in the attached N
      acyl side chain but also tolerates inversion of configuration. Our experiments
      also show that ManNAc kinase maintains its functionality, even in the absence of
      Mg(2+). From the analysis of the STD NMR-derived binding epitopes, it is
      concluded that the binding mode of the N-acylmannosamines critically depends on
      the N-acyl side chain. In conjunction with the relative binding affinities of the
      ligands obtained from STD NMR titrations, it is possible to derive a structure
      binding affinity relationship. This provides a cornerstone for the rational
      design of drugs for novel therapeutic applications by altering the sialic acid
      decorations of cell walls.

PMID- 15498764
TI  - Characterization of ligand binding to the bifunctional key enzyme in the sialic
      acid biosynthesis by NMR: I. Investigation of the UDP-GlcNAc 2-epimerase
      functionality.
AB  - The bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine
      kinase is the key enzyme for the biosynthesis of sialic acids. As terminal
      components of glycoconjugates, sialic acids are associated with a variety of
      pathological processes such as inflammation and cancer. For the first time, this
      study reveals characteristics of the interaction of the epimerase site of the
      enzyme with its natural substrate, UDP-N-acetylglucosamine (UDP-GlcNAc) and
      derivatives thereof at atomic resolution. Saturation transfer difference NMR
      experiments were crucial in obtaining ligand binding epitopes and to rank ligands
      according to their binding affinities. Employing a fragment based approach, it
      was possible to assign the major component of substrate recognition to the UDP
      moiety. In particular, the binding epitopes of the uridine moieties of UMP, UDP,
      UDP-GalNAc, and UDP-GlcNAc are rather similar, suggesting that the binding mode
      of the UDP moiety is the same in all cases. In contrast, the hexopyranose units
      of UDP-GlcNAc and UDP-GalNAc display small differences reflecting the inability
      of the enzyme to process UDP-GalNAc. Surprisingly, saturation transfer difference
      NMR titrations show that UDP has the largest binding affinity to the epimerase
      site and that at least one phosphate group is required for binding. Consequently,
      this study provides important new data for rational drug design.

PMID- 15498765
TI  - Evidence for domain-specific recognition of SK and Kv channels by MTX and HsTx1
      scorpion toxins.
AB  - Maurotoxin (MTX) and HsTx1 are two scorpion toxins belonging to the alpha-KTx6
      structural family. These 34-residue toxins, cross-linked by four disulfide
      bridges, share 59% sequence identity and fold along the classical alpha/beta
      scaffold. Despite these structural similarities, they fully differ in their
      pharmacological profiles. MTX is highly active on small (SK) and intermediate
      (IK) conductance Ca(2+)-activated (K(+)) channels and on voltage-gated Kv1.2
      channel, whereas HsTx1 potently blocks voltage-gated Kv1.1 and Kv1.3 channels
      only. Here, we designed and chemically produced MTX-HsTx1, a chimera of both
      toxins that contains the N-terminal helical region of MTX (sequence 1-16) and the
      C-terminal beta-sheet region of HsTx1 (sequence 17-34). The three-dimensional
      structure of the peptide in solution was solved by (1)H NMR. MTX-HsTx1 displays
      the activity of MTX on SK channel, whereas it exhibits the pharmacological
      profile of HsTx1 on Kv1.1, Kv1.2, Kv1.3, and IK channels. These data demonstrate
      that the helical region of MTX exerts a key role in SK channel recognition,
      whereas the beta-sheet region of HsTx1 is crucial for activity on all other
      channel types tested.

PMID- 15498766
TI  - Stimulation of vascular smooth muscle cell proliferation and migration by
      apolipoprotein(a) is dependent on inhibition of transforming growth factor-beta
      activation and on the presence of kringle IV type 9.
AB  - Elevated plasma concentrations of lipoprotein(a) are a risk factor for the
      development of a variety of atherosclerotic disorders. Despite intensive study,
      the mechanisms by which lipoprotein(a) promotes these disorders remain to be
      unequivocally defined. It has been demonstrated that lipoprotein(a), through its
      unique constituent apolipoprotein(a) (apo(a)), stimulates vascular smooth muscle
      cell (SMC) migration and proliferation. These effects arise from the ability of
      apo(a) to inhibit the formation of active transforming growth factor beta (TGF
      beta) from its latent precursor, which in turn is caused by the ability of apo(a)
      to decrease the formation of plasmin from its precursor plasminogen. We utilized
      a battery of recombinant apo(a) variants that represent systematic deletions of
      the various domains in the molecule to further probe the mechanism underlying the
      effect of apo(a) on SMC responses. All recombinant apo(a) variants that contained
      kringle IV type 9 were able to stimulate SMC proliferation and migration and to
      decrease the formation of active TGF-beta; conversely all recombinant apo(a)
      variants lacking kringle IV type 9 had no effect on these parameters. The kringle
      IV type 9-dependent effects of apo(a) on SMC proliferation required the presence
      of plasminogen, suggesting for the first time that this kringle mediates the
      ability of apo(a) to inhibit pericellular plasmin formation.

PMID- 15498767
TI  - A novel signaling pathway mediates the inhibition of CCL3/4 expression by
      prostaglandin E2.
AB  - In response to pathogen-associated molecular patterns, dendritic cells initiate
      an innate immune response characterized by expression and release of
      proinflammatory cytokines and chemokines. The extent of the inflammatory response
      is limited by various endogenous factors, including lipid mediators such as
      prostaglandin E(2) (PGE(2)). We described previously the inhibitory effect of
      PGE(2) on the expression and release of the inflammatory chemokines CCL3 and CCL4
      from activated dendritic cells. In this study we describe a novel PGE(2)
      signaling pathway that proceeds through EP-2 --> cAMP --> EPAC -->
      phosphatidylinositol 3-kinase --> protein kinase B --> GSK-3 and results in
      increased DNA binding of the CCAAT displacement protein (CDP), a potent mammalian
      transcriptional repressor. The direct link between CDP and CCL3/4 transcription
      was established in knock-down experiments using CDP small interference RNA.

PMID- 15498768
TI  - Phosphorylation of candida glabrata ATP-binding cassette transporter Cdr1p
      regulates drug efflux activity and ATPase stability.
AB  - Fungal ATP-binding cassette transporter regulation was investigated using Candida
      glabrata Cdr1p and Pdh1p expressed in Saccharomyces cerevisiae. Rephosphorylation
      of Pdh1p and Cdr1p was protein kinase A inhibitor-sensitive but responded
      differentially to Tpk isoforms, stressors, and glucose concentration. Cdr1p
      Ser(307), which borders the nucleotide binding domain 1 ABC signature motif, and
      Ser(484), near the membrane, were dephosphorylated on glucose depletion and
      independently rephosphorylated during glucose exposure or under stress. The S484A
      enzyme retained half the wild type ATPase activity without affecting azole
      resistance, but the S307A enzyme was unstable to plasma membrane isolation.
      Studies of pump function suggested conformational interaction between Ser(484)
      and Ser(307). An S307A/S484A double mutant, which failed to efflux the Cdr1p
      substrate rhodamine 6G, had a fluconazole susceptibility 4-fold greater than the
      Cdr1p expressing strain, twice that of the S307A mutant, but 64-fold less than
      the control null strain. Stable intragenic suppressors indicative of homodimer
      nucleotide binding domain 1-nucleotide binding domain 1 interactions partially
      restored rhodamine 6G pumping and increased fluconazole and rhodamine 6G
      resistance in the S307A/S484A mutant. Nucleotide binding domain 1 of Cdr1p is a
      sensor of important physiological stimuli.

PMID- 15498769
TI  - Increased phosphatidylcholine production but disrupted glycogen metabolism in
      fetal type II cells of mice that overexpress CTP:phosphocholine
      cytidylyltransferase.
AB  - CTP:phosphocholine cytidylyltransferase (CCT) is a rate-determining enzyme in the
      de novo synthesis of phosphatidylcholine (PtdCho). Alveolar type II cells
      synthesize large quantities of disaturated PtdCho, the surface-active agent of
      pulmonary surfactant, particularly at late gestation when the lung prepares
      itself for postnatal air breathing. To clarify the role of CCTalpha in lung
      surfactant maturation, we overexpressed CCTalpha(1-367) using the surfactant
      protein-C promoter. Lungs of transgenic mice were analyzed at day 18 of gestation
      (term = 19 days). Overexpression of CCTalpha(1-367) increased the synthesis and
      content of PtdCho in fetal type II cells isolated from the transgenic mice. Also,
      PtdCho content of fetal lung fluid was increased. No changes in surfactant
      protein content were detected. Interestingly, fetal type II cells of transgenic
      mice contained more glycogen than control cells. Incorporation studies with [U
      (14)C]glucose demonstrated that overexpression of CCTalpha(1-367) in fetal type
      II cells increased glycogen synthesis without affecting glycogen breakdown. To
      determine which domain contributes to this glycogen phenotype, two additional
      transgenes were created overexpressing either CCTalpha(1-239) or CCTalpha(239
      367). Glycogen synthesis and content were increased in fetal type II cells
      expressing CCTalpha(239-367) but not CCTalpha(1-239)(.) We conclude that
      overexpression of CCTalpha increases surfactant PtdCho synthesis without
      affecting surfactant protein levels but that it disrupts glycogen metabolism in
      differentiating type II cells via its regulatory domain.

PMID- 15498770
TI  - Localization of nitration and chlorination sites on apolipoprotein A-I catalyzed
      by myeloperoxidase in human atheroma and associated oxidative impairment in ABCA1
      dependent cholesterol efflux from macrophages.
AB  - We recently reported that apolipoprotein A-I (apoA-I), the major protein
      component of high density lipoprotein, is a selective target for myeloperoxidase
      (MPO)-catalyzed nitration and chlorination in both and serum of subjects with
      cardiovascular disease. We further showed that the extent of both apoA-I
      nitration and chlorination correlated with functional impairment in reverse
      cholesterol transport activity of the isolated lipoprotein. Herein we used tandem
      mass spectrometry to map the sites of MPO-mediated apoA-I nitration and
      chlorination in vitro and in vivo and to relate the degree of site-specific
      modifications to loss of apoA-I lipid binding and cholesterol efflux functions.
      Of the seven tyrosine residues in apoA-I, Tyr-192, Tyr-166, Tyr-236, and Tyr-29
      were nitrated and chlorinated in MPO-mediated reactions. Site-specific liquid
      chromatography-mass spectrometry quantitative analyses demonstrated that the
      favored modification site following exposure to MPO-generated oxidants is Tyr
      192. MPO-dependent nitration and chlorination both proceed with Tyr-166 as a
      secondary site and with Tyr-236 and Tyr-29 modified only minimally. Parallel
      functional studies demonstrated dose-dependent losses of ABCA1-dependent
      cholesterol acceptor and lipid binding activities with apoA-I modification by
      MPO. Finally tandem mass spectrometry analyses showed that apoA-I in human
      atherosclerotic tissue is nitrated at the MPO-preferred sites, Tyr-192 and Tyr
      166. The present studies suggest that site-specific modifications of apoA-I by
      MPO are associated with impaired lipid binding and ABCA1-dependent cholesterol
      acceptor functions, providing a molecular mechanism that likely contributes to
      the clinical link between MPO levels and cardiovascular disease risk.

PMID- 15498771
TI  - Preapoptotic chromatin condensation upstream of the mitochondrial checkpoint.
AB  - When added for a short period (2-4 h) to cells, the kinase inhibitor
      staurosporine (STS), can trigger double strand breaks, the formation of nuclear
      foci containing phosphorylated H2AX, Chk2, and p53, a decrease in transcription,
      and a minor degree of peripheral chromatin condensation. This "preapoptotic
      chromatin condensation" (PACC) occurs before mitochondrial membrane
      permeabilization (MMP) and caspase activation become detectable and is not
      inhibited by Z-VAD-fmk or Bcl-2. PACC is followed by classical apoptosis, when
      cells are cultured overnight, even when STS is removed from the system. After
      overnight incubation, STS-pretreated cells manifest mitochondrial cytochrome c
      release, caspase activation, phosphatidylserine exposure, and apoptotic DNA
      fragmentation. Caspase or MMP inhibitors did not influence the advent of PACC yet
      did suppress the evolution of PACC toward apoptosis. Importantly, two unrelated
      MMP inhibitors (viral mitochondrial inhibitor of apoptosis (vMIA) from
      cytomegalovirus and mitochondrion-targeted Bcl-2) had a larger range of effects
      than the pan-caspase inhibitor Z-VAD-fmk. Caspase inhibition simply prevented the
      transition from PACC to apoptosis yet did not reverse PACC and did not restore
      transcription. In contrast, Bcl-2 and vMIA allowed for the repair of the DNA
      lesions, correlating with the reestablishment of active transcription. PACC could
      also be induced by a gross perturbation of RNA synthesis or primary DNA damage.
      Again, inhibition of MMP (but not that of caspases) reversed PACC induced by
      these stimuli. In synthesis, our data reveal the unexpected capacity of STS to
      induce DNA lesions and suggest qualitative differences in the cytoprotective and
      DNA repair-inducing potential of different apoptosis inhibitors.

PMID- 15498772
TI  - Unfolding events in the water-soluble monomeric Cry1Ab toxin during transition to
      oligomeric pre-pore and membrane-inserted pore channel.
AB  - The insecticidal crystal (Cry) proteins produced by Bacillus thuringiensis
      undergo several conformational changes from crystal inclusion protoxins to
      membrane-inserted channels in the midgut epithelial cells of the target insect.
      Here we analyzed the stability of the different forms of Cry1Ab toxin, monomeric
      toxin, pre-pore complex, and membrane-inserted channel, after urea and thermal
      denaturation by monitoring intrinsic tryptophan fluorescence of the protein and 1
      anilinonaphthalene-8-sulfonic acid binding to partially unfolded proteins. Our
      results showed that flexibility of the monomeric toxin was dramatically enhanced
      upon oligomerization and was even further increased by insertion of the pre-pore
      into the membrane as shown by the lower concentration of chaotropic agents needed
      to achieve unfolding of the oligomeric species. The flexibility of the toxin
      structures is further increased by alkaline pH. We found that the monomer-monomer
      interaction in the pre-pore is highly stable because urea promotes oligomer
      denaturation without disassembly. Partial unfolding and limited proteolysis
      studies demonstrated that domains II and III were less stable and unfold first,
      followed by unfolding of the most stable domain I, and also that domain I is
      involved in monomer-monomer interaction. The thermal-induced unfolding and
      analysis of energy transfer from Trp residues to bound 1-anilinonaphthalene-8
      sulfonic acid dye showed that in the membrane-inserted pore domains II and III
      are particularly sensitive to heat denaturation, in contrast to domain I,
      suggesting that only domain I may be inserted into the membrane. Finally, the
      insertion into the membrane of the oligomeric pre-pore structure was not affected
      by pH. However, a looser conformation of the membrane-inserted domain I induced
      by neutral or alkaline pH correlates with active channel formation. Our studies
      suggest for the first time that a more flexible conformation of Cry toxin could
      be necessary for membrane insertion, and this flexible structure is induced by
      toxin oligomerization. Finally the alkaline pH found in the midgut lumen of
      lepidopteran insects could increase the flexibility of membrane-inserted domain I
      necessary for pore formation.

PMID- 15498773
TI  - Plant UBX domain-containing protein 1, PUX1, regulates the oligomeric structure
      and activity of arabidopsis CDC48.
AB  - p97/CDC48 is a highly abundant hexameric AAA-ATPase that functions as a molecular
      chaperone in numerous diverse cellular activities. We have identified an
      Arabidopsis UBX domain-containing protein, PUX1, which functions to regulate the
      oligomeric structure of the Arabidopsis homolog of p97/CDC48, AtCDC48, as well as
      mammalian p97. PUX1 is a soluble protein that co-fractionates with non-hexameric
      AtCDC48 and physically interacts with AtCDC48 in vivo. Binding of PUX1 to AtCDC48
      is mediated through the UBX-containing C-terminal domain. However, disassembly of
      the chaperone is dependent upon the N-terminal domain of PUX1. These findings
      provide evidence that the assembly and disassembly of the hexameric p97/CDC48
      complex is a dynamic process. This new unexpected level of regulation for
      p97/CDC48 was demonstrated to be critical in vivo as pux1 loss-of-function
      mutants display accelerated growth relative to wild-type plants. These results
      suggest a role for AtCDC48 and PUX1 in regulating plant growth.

PMID- 15498774
TI  - Transcriptional activity of serum amyloid A-activating factor-1 is regulated by
      distinct functional modules.
AB  - Serum amyloid A-activating transcription factor-1 (SAF-1) plays a major role in
      regulating transcription of several inflammation-responsive genes, including SAA
      and matrix metalloproteinase-1, that are implicated in the pathogenesis of
      reactive secondary amyloidosis, atherosclerosis, and arthritis. SAF-1 is a 477
      amino acid protein with six zinc fingers. Its activation during inflammatory
      condition by a phosphorylation event that leads to an altered structure suggested
      possible structural modification of this protein as a leading cause of higher
      activity. However, no information is available regarding structural features that
      might regulate its activity. Here, we have characterized its functional domains,
      delineating activation and repression modules, DNA binding, and nuclear
      localization activities. Using GAL4AD chimeras and a DNA-binding assay with
      proteins prepared from various deletion constructs, the core DNA-binding domain
      of SAF-1 is mapped between amino acids 282 and 361, which contain second, third,
      and fourth zinc fingers. Results from several deletion and point mutants using
      green fluorescent protein reporter show that SAF-1 contains two independent
      nuclear localization signals; one is composed of a stretch of basic amino acids,
      and the other is a bipartite signal located within the core DNA-binding domain.
      SAF-1 contains several negative and positively functioning transactivation
      modules clustered at the two ends of this protein. Removal of any one of the
      terminal negative modules renders the SAF-1 protein functionally very active.
      These findings suggest that the terminal repression modules act in conjunction to
      regulate the functional activity of this protein.

PMID- 15498775
TI  - Isolation of unique STAT5 targets by chromatin immunoprecipitation-based gene
      identification.
AB  - STAT5a and STAT5b are two highly related transcription factors that control
      essential cellular functions. Several STAT5 targets are known, although it is
      likely that most remain uncharacterized. To identify a more complete set of STAT5
      regulated genes, we used a modification of the chromatin immunoprecipitation
      procedure, which does not presuppose any information regarding these targets.
      Employing Ba/f3 cells in which STAT5 is activated by interleukin-3, we have
      identified novel STAT5 binding sites that may be regulatory regions for nearby
      genes. These sites are typically found far from transcription start sites, and
      most do not contain CpG islands, indicating that they are not in traditional
      promoter regions. Nonetheless, when the expression of genes near these STAT5
      binding sites was examined, all were expressed in Ba/f3 cells, and most were
      modulated by interleukin-3. Furthermore, genes identified by this strategy show
      unique expression patterns in acute leukemias, tumors characterized by activated
      STAT5. Whereas both STAT5 isoforms bound to all promoters tested, STAT5a and
      STAT5b bound with different kinetics, suggesting that at least some of the
      differences between the functions of these two proteins are mediated by their DNA
      binding activity. Therefore, this method of transcription factor target
      identification represents an effective strategy to isolate transcription factor
      targets in an unbiased fashion, and it has revealed many novel STAT5-dependent
      regulatory regions outside of traditional promoters.

PMID- 15498776
TI  - Poly(ADP-ribose) polymerase-1 is a negative regulator of HIV-1 transcription
      through competitive binding to TAR RNA with Tat.positive transcription elongation
      factor b (p-TEFb) complex.
AB  - Human immunodeficiency virus, type 1 (HIV-1) transcription is regulated by a
      virus-encoded protein, Tat, which forms a complex with a host cellular factor,
      positive transcription elongation factor b (P-TEFb). When this complex binds to
      TAR RNA synthesized from the HIV-1 long terminal repeat promoter element,
      transcription is trans-activated. In this study we showed that, in host cells,
      HIV-1 transcription is negatively regulated by competition of poly(ADP-ribose)
      polymerase-1 (PARP-1) with Tat.P-TEFb for binding to TAR RNA. PARP-1, which has a
      high affinity for TAR RNA (K(D) = 1.35 x 10(-10) M), binds to the loop region of
      TAR RNA and displaces Tat or Tat.P-TEFb from the RNA. In vitro transcription
      assays showed that this displacement leads to suppression of Tat-mediated trans
      activation of transcription. Furthermore in vivo expression of luciferase or
      destabilized enhanced green fluorescent protein genes under the control of the
      HIV-1 long terminal repeat promoter was suppressed by PARP-1. Thus, these results
      suggest that PARP-1 acts as a negative regulator of HIV-1 transcription through
      competitive binding with Tat or the Tat.P-TEFb complex to TAR RNA.

PMID- 15498777
TI  - In vivo dynamics of EBNA1-oriP interaction during latent and lytic replication of
      Epstein-Barr virus.
AB  - The Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is required for
      maintenance of the viral genome DNA during the latent phase of EBV replication
      but continues to be synthesized after the induction of viral productive
      replication. An EBV genome-wide chromatin immunoprecipitation assay revealed that
      EBNA1 constantly binds to oriP of the EBV genome during not only latent but also
      lytic infection. Although the total levels of EBNA1 proved constant throughout
      the latter, the levels of the oriP-bound form were increased as lytic infection
      proceeded. EBV productive DNA replication occurs at discrete sites in nuclei,
      called replication compartments, where viral replication proteins are clustered.
      Confocal laser microscopic analyses revealed that whereas EBNA1 was distributed
      broadly in nuclei as fine punctate dots during the latent phase of infection, the
      protein became redistributed to the viral replication compartments and localized
      as distinct spots within and/or nearby the compartments after the induction of
      lytic replication. Taking these findings into consideration, oriP regions of the
      EBV genome might be organized by EBNA1 into replication domains that may set up
      scaffolding for lytic replication and transcription.

PMID- 15498778
TI  - Involvement of poly(ADP-ribose) polymerase-1 and XRCC1/DNA ligase III in an
      alternative route for DNA double-strand breaks rejoining.
AB  - The efficient repair of DNA double-strand breaks (DSBs) is critical for the
      maintenance of genomic integrity. In mammalian cells, the nonhomologous end
      joining process that represents the predominant repair pathway relies on the DNA
      dependent protein kinase (DNA-PK) and the XRCC4-DNA ligase IV complex.
      Nonetheless, several in vitro and in vivo results indicate that mammalian cells
      use more than a single end-joining mechanism. While searching for a DNA-PK
      independent end-joining activity, we found that the pretreatment of DNA-PK
      proficient and -deficient rodent cells with an inhibitor of the poly(ADP-ribose)
      polymerase-1 enzyme (PARP-1) led to increased cytotoxicity of the highly
      efficient DNA double-strand breaking compound calicheamicin gamma1. In addition,
      the repair kinetics of the DSBs induced by calicheamicin gamma1 was delayed both
      in PARP-1-proficient cells pretreated with the PARP-1 inhibitor and in PARP-1
      deficient cells. In order to get new insights into the mechanism of an
      alternative route for DSBs repair, we have established a new synapsis and end
      joining two-step assay in vitro, operating on DSBs with either nuclear protein
      extracts or recombinant proteins. We found an end-joining activity independent of
      the DNA-PK/XRCC4-ligase IV complex but that actually required a novel synapsis
      activity of PARP-1 and the ligation activity of the XRCC1-DNA ligase III complex,
      proteins otherwise involved in the base excision repair pathway. Taken together,
      these results strongly suggest that a PARP-1-dependent DSBs end-joining activity
      may exist in mammalian cells. We propose that this mechanism could act as an
      alternative route of DSBs repair that complements the DNA-PK/XRCC4/ligase IV
      dependent nonhomologous end-joining.

PMID- 15498779
TI  - Ovarian senescence in the rhesus monkey (Macaca mulatta).
AB  - BACKGROUND: A decline in fertility is evident in human females past their middle
      thirties. This 'reproductive senescence', marked by a sharp decline in pregnancy
      rates, may be attributed to reductions in numbers of available oocytes and their
      quality. Because Old World primates exhibit ovarian morphology and physiological
      control and timing of menstrual cycles closely resembling those of humans, the
      current study investigated the rhesus macaque as a potential model for human
      reproductive senescence. METHODS: Ovaries collected from females aged 1-25 years
      and divided into five age groups were analysed histologically. RESULTS: General
      ovarian morphology demonstrated significant changes as the females approached
      menopause. The proportions of primordial and primary follicles all demonstrated
      significant differences across age groups (primordial: 77.1, 79.9, 69.7, 62.9,
      55.1%; primary: 21.5, 18.8, 28.5, 35.2, 43.1% for age groups 1 to 5 respectively;
      P<0.0001 for both). Samples from females approaching or undergoing the menopausal
      transition (aged 20-25 years) demonstrated evidence of ovarian senescence, having
      scattered and atretic follicles, low numbers of primordial follicles and reduced
      stromal tissue. CONCLUSION: This study supports the value of the rhesus monkey as
      a model for reproductive ageing because its ovary undergoes follicular reservoir
      depletion similar to that seen in humans.

PMID- 15498780
TI  - Embryonic soluble HLA-G as a marker of developmental potential in embryos.
AB  - BACKGROUND: In human reproduction, embryo implantation is complex and poorly
      understood. At present, no single markers are used in routine treatment to assay
      biochemical functions of the human embryo. Soluble human leukocyte antigen-G
      (sHLA-G) could be considered a possible marker of embryo developmental potential.
      It is localized primarily on the extravillous trophoblast, making this antigen a
      potential mediator of immune interaction at the maternal-fetal interface during
      gestation. METHODS: Soluble-HLA-G levels were evaluated by an enzyme-linked
      immunosorbent assay (ELISA) employing monoclonal antibody MEM-G9. It was
      evaluated in 318 media of single embryo cultures. We correlated the presence of
      sHLA-G with embryo morphology and the pregnancy obtained in that treatment cycle.
      RESULTS: No correlation was found between embryo morphology and sHLA-G levels.
      Pregnancy was observed only when the medium of at least one transferred embryo
      contained sHLA-G. In 26 out of 66 patients, none of the obtained embryos showed
      any detectable sHLA-G molecules and no pregnancy occurred. CONCLUSIONS: From our
      results, we propose sHLA-G as a potential marker of embryo development: the sHLA
      G ELISA can be a useful biochemical assay in addition to embryo morphology in
      embryo selection for transfer in IVF treatment if there are other embryos with
      the same morphology.

PMID- 15498781
TI  - Partial deletions in the AZFc region of the Y chromosome occur in men with
      impaired as well as normal spermatogenesis.
AB  - BACKGROUND: Partial deletions of the AZFc region of the Y chromosome were
      reported to be a significant risk factor for oligo-/azoospermia. In this study,
      we assessed the occurrence and frequency of partial AZFc microdeletions in
      patients with spermatogenic failure and in controls with normal spermatogenesis.
      METHODS: In a retrospective study design, gr/gr, b1/b3 and b2/b3 deletions were
      analysed by multiplex PCR in 170 men with normal spermatogenesis and 348 men with
      non-obstructive oligo-/azoospermia. RESULTS: gr/gr deletions were found in 14 men
      with oligozoospermia or azoospermia (4.0%) and in three normozoospermic men
      (1.8%) (NS). b1/b3 deletions were found both in controls (n=1) and in patients
      (n=1). b2/b3 deletions were significantly more frequent in the normozoospermic
      (five out of 170) than in the oligo-/azoospermic men (two out of 348). Three
      novel partial AZFc deletion patterns were found in four oligo-/azoospermic men.
      No correlation with semen or other clinical parameters was found. CONCLUSIONS:
      The frequency of gr/gr deletions is not significantly increased in men with oligo
      /azoospermia, indicating that they are not sufficient per se to cause
      spermatogenetic impairment and infertility. b1/b3 and b2/b3 deletions are
      probably irrelevant for spermatogenesis. Novel deletion patterns found
      exclusively in infertile men suggest that other, still unexplored partial
      deletions might contribute to spermatogenic failure.

PMID- 15498782
TI  - A comparative study of three-dimensional saline infusion sonohysterography and
      diagnostic hysteroscopy for the classification of submucous fibroids.
AB  - BACKGROUND: The purpose of this study was to compare three-dimensional saline
      infusion sonohysterography (3D SIS) and diagnostic hysteroscopy for the diagnosis
      and classification of submucous uterine fibroids. METHODS: This was a prospective
      double-blind study of 49 women who presented with a history of menorrhagia,
      diagnosed on non-enhanced two-dimensional ultrasonography with submucous
      fibroids. Fibroids were classified on 3D SIS according to the proportion of
      fibroid contained within the endometrial cavity, using the European Society of
      Hysteroscopy Classification of Submucous Fibroids. These results were then
      compared with the findings at diagnostic hysteroscopy. RESULTS: A total of 61
      submucous fibroids was identified in 49 symptomatic women. Diagnostic
      hysteroscopy confirmed these findings in all cases. There was agreement between
      the two methods in 11/12 cases of Type 0 fibroids (92%), 34/37 (92%) of Type I
      fibroids and 9/12 (75%) of Type II fibroids. The overall level of agreement was
      good with a kappa value of 0.80. CONCLUSIONS: There is a good overall agreement
      between 3D SIS and diagnostic hysteroscopy in classification of submucous
      fibroids. Agreement is better in cases where a greater proportion of the fibroid
      is contained within the uterine cavity.

PMID- 15498783
TI  - Oncogene regulation of tumor suppressor genes in tumorigenesis.
AB  - We attempted to demonstrate whether there is an epigenetic link between oncogenes
      and tumor suppression genes in tumorigenesis. We designed a high throughput model
      to identify a candidate group of tumor suppressor genes potentially regulated by
      oncogenes. Gene expression profiling of mock-transfected versus v-src-transfected
      3Y1 rat fibroblasts identified significant overexpression of DNA
      methyltransferase 1, the enzyme responsible for aberrant genome methylation, in v
      src-transfected fibroblasts. Secondary microarray analyses identified a number of
      candidate tumor suppressor genes that were down-regulated by v-src but were also
      re-expressed following treatment with 5-aza-2'-deoxycytidine, a potent
      demethylating agent. This candidate group included both tumor suppressor genes
      that are known to be silenced by DNA hypermethylation and those that have not
      been previously identified with promoter hypermethylation. To further validate
      our model, we identified tsg, a tumor suppressor gene that was shown to be down
      regulated by v-src and found to harbor dense promoter hypermethylation. Our model
      demonstrates a cooperative relationship between oncogenes and tumor suppressor
      genes mediated through promoter hypermethylation.

PMID- 15498784
TI  - Prostate carcinogenesis and inflammation: emerging insights.
AB  - Prostate cancer remains a significant health concern for men throughout the
      world. Recently, there has developed an expanding multidisciplinary body of
      literature suggesting a link between chronic inflammation and prostate cancer. In
      support of this hypothesis, population studies have found an increased relative
      risk of prostate cancer in men with a prior history of certain sexually
      transmitted infections or prostatitis. Furthermore, genetic epidemiological data
      have implicated germline variants of several genes associated with the
      immunological aspects of inflammation in modulating prostate cancer risk. The
      molecular pathogenesis of prostate cancer has been characterized by somatic
      alterations of genes involved in defenses against inflammatory damage and in
      tissue recovery. A novel putative prostate cancer precursor lesion, proliferative
      inflammatory atrophy, which shares some molecular traits with prostate
      intraepithelial neoplasia and prostate cancer, has been characterized. Here, we
      review the evidence associating chronic inflammation and prostate cancer and
      consider a number of animal models of prostate inflammation that should allow the
      elucidation of the mechanisms by which prostatic inflammation could lead to the
      initiation and progression of prostate cancer. These emerging insights into
      chronic inflammation in the etiology of prostate carcinogenesis hold the promise
      of spawning new diagnostic and therapeutic modalities for men with prostate
      cancer.

PMID- 15498785
TI  - Oltipraz regulates different categories of genes relevant to chemoprevention in
      human hepatocytes.
AB  - Numerous chemical compounds are cytotoxic or carcinogenic to human beings and
      attention is now focusing on preventative strategies. One agent, oltipraz (OPZ),
      regarded as one of the most promising chemoprotectors, has been shown to be a
      potent inducer of phase II enzymes involved in the detoxification of carcinogens,
      including aflatoxins. However, little is known about its effects on global gene
      expression in human cells. Thus, we used microarrays and reverse transcription
      quantitative polymerase chain reaction to test the effects of OPZ on the overall
      pattern of mRNA expression of multiple metabolic pathways in human hepatocytes in
      primary culture. Our results show for the first time that OPZ significantly
      alters the expression of human genes within different functional categories
      (detoxification of xenobiotics, antioxidant defences, xenobiotic transport, cell
      cycle and stress responses), at both the mRNA and protein levels, some of which
      are highly relevant to chemoprevention. Amongst these genes, several have never
      been described as being regulated by OPZ before. We also demonstrate variations
      in response to OPZ, depending on the individual from whom the cells were derived,
      that might potentially contribute to differences in efficacy of chemopreventive
      treatments between individuals. Moreover, comparison of our results with those
      obtained in rodents demonstrates species differences in response to OPZ for some
      genes, underlying the importance of studies on human cells to predict the effects
      of chemopreventive agents.

PMID- 15498786
TI  - Chemopreventive N-(4-hydroxyphenyl)retinamide (fenretinide) targets deregulated
      NF-{kappa}B and Mat1A genes in the early stages of rat liver carcinogenesis.
AB  - Cell-cycle deregulation is an early event of hepatocarcinogenesis. We evaluated
      the role of changes in activity of nuclear factor kappaB (NF-kappaB) and some
      related pathways in this alteration, and the interference of N-(4
      hydroxyphenyl)retinamide (HPR), a retinoid chemopreventive for various cancer
      types, with these molecular mechanisms and the evolution of preneoplastic liver
      to cancer. Male F344 rats, initiated according to the 'resistant hepatocyte'
      model of liver carcinogenesis, received weekly 840 nmol of liposomal HPR (SL
      HPR)/100 g body wt or empty liposomes, between 5 and 25 weeks after initiation.
      Inhibition of DNA synthesis and induction of apoptosis occurred in pre-cancerous
      lesions, 7-147 days after starting SL-HPR, and a decrease in carcinoma incidence
      and multiplicity was observed 25 weeks after arresting treatment. An increase in
      NF-kappaB expression and binding activity, and under-expression of the inhibitor
      kappaB-alpha (IkappaB-alpha) were found in preneoplastic liver and neoplastic
      nodules, 5 and 25 weeks after initiation, respectively. These lesions also showed
      low expression of Mat1A and low activity of methionine adenosyltransferase I/III,
      whose reaction product, S-adenosyl-l-methionine, enhances IkappaB-alpha
      expression. SL-HPR prevented these changes and induced a decrease in expression
      of iNos, c-myc, cyclin D1 and Vegf-A genes, that were over-expressed in
      preneoplastic liver and nodules, and a decrease in Bcl-2/Bax, Bcl-2/Bad and Bcl
      xL/Bax mRNA ratios with respect to the lesions of control rats. Liposomes alone
      did not influence the parameters tested. These results indicate that signal
      transduction pathways controlled by NF-kappaB, nitric oxide and S-adenosyl-l
      methionine are deregulated in pre-cancerous lesions. Recovery from these
      alterations by SL-HPR is associated with chemoprevention of hepatocarcinogenesis.
      Overall, these studies elucidate some molecular changes, in early stages of
      hepatocarcinogenesis, and underline their pathogenetic role. Moreover, they
      demonstrate a partially new mechanism of HPR chemopreventive effect and indicate
      the potential clinical relevance of this compound for prevention of
      hepatocellular carcinoma.

PMID- 15498787
TI  - NQO1 T allele associated with decreased risk of later age at diagnosis lung
      cancer among never smokers: results from a population-based study.
AB  - The NAD(P)H:quinone oxidoreductase 1 gene, NQO1, contains a C to T transition at
      amino acid codon 187, which results in very low enzymatic activity. Previous
      studies of the association between NQO1 genotype and lung cancer have had mixed
      findings. This population-based case control study examines the association
      between NQO1 genotype and lung cancer in the largest sample of never smokers
      (<100 cigarettes, lifetime) to date. Cases (n = 161) were identified through the
      metropolitan Detroit Surveillance, Epidemiology and End Results (SEER) program,
      and 5-year age- and race-matched population-based controls (n = 173) were
      identified using random digit dialing. Allele frequencies of C and T,
      respectively, were 0.79 and 0.21 in Caucasians, and 0.84 and 0.16 in African
      Americans. Among those diagnosed aged >/=50 years, C/T and T/T genotyped
      individuals had 0.48 times lower lung cancer risk than individuals with C/C
      genotype (95% CI: 0.27-0.87). There was a non-significant suggestion of a
      protective effect associated with the T allele among those with a history of
      environmental tobacco smoke exposure (OR = 0.57, 95% CI: 0.32-1.03) but not among
      those without (OR = 0.98, 95% CI: 0.41-2.38). Sex, race, family history of lung
      cancer and histologic type did not modify the effect of NQO1 genotype on lung
      cancer risk. The observed risk reductions may be attributable to the greatly
      reduced procarcinogen activating of NAD(P)H:quinone oxidoreductase 1 in
      individuals with at least one copy of the T allele.

PMID- 15498788
TI  - Antitumor promotional effects of a novel intestinal bacterial metabolite (IH-901)
      derived from the protopanaxadiol-type ginsenosides in mouse skin.
AB  - Epidemiological studies have demonstrated that ginseng intake decreases the risk
      of cancer. Ginseng saponins (ginsenosides) have been regarded as principal
      components responsible for the majority of pharmacological activities exerted by
      ginseng. IH-901 [20-O-beta-d-glucopyranosyl-20(S)-protopanaxadiol], an intestinal
      bacterial metabolite derived from protopanaxadiol-type saponins of Panax ginseng
      C.A. Meyer, has been reported to possess antitumor effects, including inhibition
      of invasion, metastasis and angiogenesis and induction of tumor cell apoptosis.
      Tumor promotion often accompanies an elevated ornithine decarboxylase (ODC)
      activity, acute inflammation and induction of cyclooxygenase-2 (COX-2) activity.
      Here we examined the effects of IH-901 on tumor promotion and related molecular
      events in mouse skin in vivo. Mouse ear edema induced by the prototype tumor
      promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) was repressed by IH-901 pre
      treatment in a dose-dependent manner. Topical application of IH-901 onto shaven
      backs of female ICR mice led to the inhibition of TPA-induced expression of COX-2
      and production of prostaglandin E(2). The eukaryotic transcription factor NF
      kappaB has been involved in intracellular signaling pathways associated with
      inflammation and carcinogenesis. IH-901 pre-treatment inhibited TPA-induced
      epidermal NF-kappaB DNA binding in mouse skin, which appeared to be mediated by
      blocking phosphorylation and subsequent degradation of IkappaBalpha. In an
      attempt to elucidate the molecular mechanisms by which IH-901 inactivates NF
      kappaB, its effects on activation of upstream signaling kinases were explored. IH
      901 also inhibited the activation of ERK1/2 and Akt signaling. When IH-901 was
      treated topically prior to TPA, expression and activity of ODC were inhibited
      dose-dependently. In addition, IH-901 given prior to each topical dose of TPA
      markedly lowered the number of papillomas in mouse skin induced by 7,12
      dimethylbenz[a]anthracene. Taken together, these findings suggest that IH-901
      exerts anti-inflammatory effects by inhibiting TPA-induced COX-2 expression,
      which may contribute to its antitumor-promoting effects on mouse skin
      carcinogenesis.

PMID- 15498789
TI  - Role of a novel EGF-like domain-containing gene NGX6 in cell adhesion modulation
      in nasopharyngeal carcinoma cells.
AB  - The epidermal growth factor (EGF)-like domain is involved in receptor-ligand
      interactions, extracellular matrix formation, cell adhesion and chemotaxis.
      Nasopharyngeal carcinoma associated gene 6 (NGX6) is a novel EGF-like domain
      containing gene located at the high frequent loss of heterozygosity (LOH) region
      9p21-22 associated with nasopharyngeal carcinoma (NPC). It is down-regulated in
      NPC and its over-expression can delay the cell cycle G(0)-G(1) progression in NPC
      cells. In the present study, in situ hybridization analysis, using NPC tissue
      microarrays, showed that loss of NGX6 expression was associated with NPC lymph
      node metastasis. The Tet-on gene expression system and cDNA array techniques were
      used to profile the potential targets of NGX6. We found that NGX6 can influence
      the expression of some cell adhesion molecules in NPC cells. NGX6 can associate
      with ezrin, a linkage between the cell membrane and cytoskeleton. The NGX6
      protein was expressed on the cell surface as a glycoprotein. Ectopic induction of
      NGX6 can impair NPC cell migration and invasive ability as well as improve cell
      adhesion and gap junctional intercellular communication, and can suppress tumor
      formation in vivo. The data revealed that NGX6 plays a role in cell adhesion
      modulation in NPC cells.

PMID- 15498790
TI  - Chemopreventative effect of a cyclooxygenase-2-specific inhibitor (etodolac) on
      chemically induced biliary carcinogenesis in hamsters.
AB  - The present study was designed to evaluate whether etodolac, a cyclooxgenase-2
      (COX-2)-specific inhibitor, could prevent chemically induced biliary
      carcinogenesis in bilioenterostomized hamsters. Syrian golden hamsters were
      subjected to choledochojejunostomy and then received subcutaneous injections of N
      nitrosobis(2-oxopropyl)amine (BOP) every 2 weeks at a dose of 10 mg/kg body wt.
      BOP administration was started 4 weeks after surgery, and continued for 18 weeks.
      The animals were simultaneously orally administered etodolac three times per week
      at a dose of 10 mg/kg body wt in 0.5% methylcellose solution (etodolac group).
      The control hamsters were administered methylcellose solution alone. The hamsters
      were killed 22 weeks after surgery, and the biliary carcinomas were evaluated
      histologically. The presence and degree of cholangitis and the cell kinetic
      status of the biliary epithelium were also evaluated with special reference to
      biliary carcinogenesis. Intrahepatic bile duct carcinomas developed in 15 of 17
      (88%) hamsters in the control group, and in only six of 18 (33%) hamsters in the
      etodolac group (P < 0.01). The incidence and number of developing biliary
      carcinomas were well correlated with the degree of cholangitis, and severe
      cholangitis was evident in the controls. The cell kinetic study demonstrated that
      the proliferating cell nuclear antigen-labeling index of the biliary epithelium
      was 9.67 and 5.14% in the control and etodolac groups, respectively (P < 0.05).
      The mean levels of prostaglandin E(2) (PGE(2)) products in the liver tissue were
      14.14 +/- 3.31 pg/total protein (TP) mg in the control group, and 7.46 +/- 2.34
      pg/TP mg in the etodolac group (P < 0.05). These findings indicated that etodolac
      reduced both the occurrence of severe cholangitis and the acceleration of biliary
      epithelial cell kinetics after bilioenterostomy, resulting in the prevention of
      BOP-induced biliary carcinogenesis in hamsters. In conclusion, COX-2-specific
      inhibitor (etodolac) may be a possible agent against not only reflux cholangitis,
      but also biliary carcinoma after bilioenterostomy.

PMID- 15498791
TI  - Polymorphisms in angiotensin II type 1 receptor and angiotensin I-converting
      enzyme genes and breast cancer risk among Chinese women in Singapore.
AB  - Angiotensin II is converted from its precursor by angiotensin I-converting enzyme
      (ACE) and has been shown to mediate growth in breast cancer cell lines via ligand
      induced activity through the angiotensin II type 1 receptor (AGTR1). Earlier we
      showed that women with the low activity genotype of the ACE gene have a
      statistically significantly ( approximately 50%) reduced breast cancer risk
      compared with those possessing the high activity ACE genotype. To further test
      the hypothesis that angiotensin II participates in breast carcinogenesis through
      AGTR1, we examined genetic polymorphisms in the 5'-region of the AGTR1 gene (A
      168G, C-535T and T-825A) in relation to risk of breast cancer in 258 breast
      cancer cases and 670 female controls within the Singapore Chinese Health Study.
      Relative to the homozygotes, individual genotypes with one or two copies of the
      respective allelic variants (putative low risk genotypes) were each associated
      with an approximately 30% reduction in risk of breast cancer. Risk of breast
      cancer decreased with increasing number of low risk AGTR1 genotypes after
      adjustment for potential confounders. Relative to those carrying no low risk
      genotypes (homozygous for A, C and T alleles for the three polymorphisms,
      respectively), the odds ratios (95% confidence intervals) were 0.84 (0.51-1.37)
      for women possessing one low risk genotype and 0.68 (0.46-1.01) for women
      possessing two or three low risk genotypes (P for trend = 0.05). When both AGTR1
      and ACE gene polymorphisms were examined simultaneously, women possessing at
      least one AGTR1 low risk genotype in combination with the ACE low activity
      genotype had an odds ratio of 0.35 (95% confidence interval, 0.20-0.62) compared
      with those possessing the ACE high activity genotype and no AGTR1 low risk
      genotype. Our findings suggest that pharmacological inhibition of the angiotensin
      II effect by blockade of ACE and/or AGTR1 could be potential targets for the
      prevention and treatment of breast cancer.

PMID- 15498792
TI  - Relationship between CDX2 gene methylation and dietary factors in gastric cancer
      patients.
AB  - Epigenetic gene silencing through DNA methylation is one of the important steps
      in the mechanism underlying tumorigenesis, including in the stomach. Past
      lifestyle factors of cancer patients, such as intake of vegetables, are very
      important in affecting gastric carcinogenesis. However, the relationship between
      DNA methylation and past dietary habits in cancer patients remains largely
      unknown. The CDX2 homeobox transcription factor plays a key role in intestinal
      development, but CDX2 is also expressed in most of the intestinal metaplasia and
      part of the carcinomas of the stomach. We analyzed the methylation status of the
      CDX2 5' CpG island in gastric cancer cell lines by methylation-specific PCR
      (MSP), and then CDX2 mRNA was found to be activated after 5-aza-2'-deoxycytidine
      treatment of the methylation-positive cells. We further examined the methylation
      status of CDX2 in primary gastric carcinomas by MSP and compared it with the past
      lifestyle of the patients, including dietary habits. Methylation of CDX2 was
      found in 20 (34.5%) of the 58 male patients and one (6.7%) of the 15 female
      patients. Since the methylation frequency was low in the female patients, the
      analysis was performed only on the male cases. CDX2 methylation was correlated
      with the decreased intake of green tea and cruciferous vegetables, and also with
      full or overeating habits. These findings are consistent with epidemiological
      observations on gastric cancer. We also analyzed the methylation status of
      p16/INK4a and hMLH1, but their frequencies were not associated with dietary
      factors or other lifestyle factors. Thus, diet could be an important factor
      determining the methylation status of genes such as CDX2 and the resultant
      aberrant expression of genes involved in carcinogenesis.

PMID- 15498794
TI  - beta2 Adrenoceptor gene single nucleotide polymorphisms are associated with
      rheumatoid arthritis in northern Sweden.
AB  - BACKGROUND: beta(2) Adrenoceptor (beta(2)-AR) represents a link between the
      sympathetic nervous system and the immune system, and may be involved in human
      rheumatoid arthritis (RA). The gene encoding beta(2)-AR contains three single
      nucleotide polymorphisms (SNPs) at amino acid positions 16, 27, and 164.
      OBJECTIVE: To examine the common variants at positions 16 and 27 and their
      association with RA. METHODS: An allele-specific polymerase chain reaction to
      determine the common variants at positions 16 and 27 was used in 154 patients
      with RA and 198 ethnically matched healthy subjects from northern Sweden.
      RESULTS: Carriage of Arg16 and of Gln27 was associated with RA. Carriage of Gln27
      was associated with activity of the disease and in combination with non-carriage
      of Arg16 with higher levels of rheumatoid factor. CONCLUSION: The beta2-AR SNPs
      may thus constitute an additional non-major histocompatibility complex
      association in RA.

PMID- 15498793
TI  - UVB-induced apoptosis drives clonal expansion during skin tumor development.
AB  - The mechanism by which a single mutant cell clonally expands is usually assumed
      to involve an additional mutation in a cell cycle regulatory gene. An alternative
      mechanism for driving clonal expansion is apoptosis, which might create vacant
      stem cell compartments that can be repopulated by mutant cells. This model
      predicts that in a mouse with reduced apoptotic capacity (i) more mutated cells
      will appear initially but (ii) these cells will expand into clones more slowly
      than in wild-type animals. To test this hypothesis for ultraviolet B (UVB)
      induced skin carcinogenesis, we examined UVB-induced p53 mutant clones and tumors
      in a transgenic (Tg) mouse (K14-Survivin) with skin-specific expression of the
      apoptosis inhibitor Survivin. To limit the effects of Survivin on apoptosis,
      without affecting epidermal proliferation or differentiation, we used Survivin
      expression levels and UVB doses that resulted in a 2-fold reduction in
      keratinocyte apoptosis. After 5 weeks of chronic UVB irradiation, newly created
      p53 mutant keratinocyte clones (indicative of initial mutation frequency) were
      1.4-fold more frequent in K14-Survivin mice (P = 4 x 10(-6)). As predicted, this
      effect was reversed for clones growing by clonal expansion, which were rarer in
      Tg skin by 1.7-fold (P = 0.047). At 10 weeks large expanding Tg clones were rarer
      by a magnitude approaching the apoptosis differential (approximately 2-fold, P =
      4 x 10(-5)). Survivin expression also retarded clonal expansion at later stages
      of tumor development. By 20 weeks 95% of animals carried tumors (primarily
      papillomas), which were 1.6-fold rarer in apoptosis-defective Tg mice (P = 0.03).
      In contrast, the rate of tumors attaining large size (> or =3 mm, P = 0.048) and
      converting to carcinoma was increased approximately 2-fold in Tg mice. Thus,
      Survivin-regulated apoptosis appears to suppress two stages that involve new
      mutations, initiation and malignant conversion, yet drives clonal expansion of
      existing p53 mutant cells.

PMID- 15498795
TI  - Toll-like receptor 4 gene polymorphisms and susceptibility to juvenile idiopathic
      arthritis.
AB  - OBJECTIVES: To determine if polymorphisms within the Toll-like receptor 4 (TLR4)
      gene are associated and linked with juvenile idiopathic arthritis (JIA). To
      investigate any possible gene-gene (epistatic) interaction between TLR4 and
      macrophage migration inhibitory factor (MIF) gene polymorphisms. METHODS: 313
      simplex families (each containing one affected JIA proband) were genotyped. Two
      known functionally important single nucleotide polymorphisms (SNPs) within the
      TLR4 gene (Asp299Gly and Thr399Ile) were typed by SNaPshot ddNTP primer extension
      and capillary electrophoresis. Single point and multipoint transmission
      disequilibrium tests (TDT) were carried out through the extended TDT and TDT
      phase packages for the two TLR4 SNPs. Epistatic interaction between TLR4
      haplotypes and the previously JIA associated MIF CATT(7)-MIF-173*C promoter
      haplotype was investigated by chi(2) test and unconditional logistic regression
      in Stata version 7. RESULTS: No distortion from random inheritance was observed
      by single point analysis for TLR4 Asp299Gly (p = 0.89) or TLR4 Thr399Ile (p =
      0.40). Similarly, no distortion in transmission was seen when the TLR4 haplotypes
      were studied (p = 0.54). Additionally, no evidence for gene-gene interaction
      between TLR4 polymorphisms and the previously associated MIF gene polymorphisms
      was found (p = 0.40). CONCLUSIONS: No linkage or association was seen for
      Asp299Gly or Thr399Ile SNPs of TLR4 with JIA susceptibility. No evidence of an
      epistatic interaction between these TLR4 polymorphisms and MIF polymorphisms was
      found.

PMID- 15498796
TI  - The regulation of human MMP-13 by licofelone, an inhibitor of cyclo-oxygenases
      and 5-lipoxygenase, in human osteoarthritic chondrocytes is mediated by the
      inhibition of the p38 MAP kinase signalling pathway.
AB  - BACKGROUND: MMP-13 is one of the most important metalloproteases (MMP) involved
      in osteoarthritis. Licofelone, a novel dual inhibitor of cyclo-oxygenases (COX)
      and 5-lipoxygenase (5-LOX), can modulate MMP-13 production in human
      osteoarthritis chondrocytes. OBJECTIVE: To evaluate the impact of licofelone on
      MMP-13 expression/production, promoter, and major MAP kinase signalling pathways
      and transcription factors. METHODS: Human osteoarthritis chondrocytes were
      stimulated by interleukin 1beta (IL1beta) and treated with or without: licofelone
      (0.3, 1, or 3 mug/ml); NS-398 (10 muM; a specific COX-2 inhibitor); or BayX-1005
      (10 muM; a specific 5-LOX inhibitor). MMP-13 synthesis was determined by specific
      enzyme linked immunosorbent assay, and expression by real time polymerase chain
      reaction. The effect of licofelone on the MMP-13 promoter was studied through
      transient transfection; dexamethasone (10(-7) M) was used as comparison. The
      effect on IL1beta induced MMP-13 signalling pathways was determined using
      specific ELISA for phosphorylated MAP kinases and transcription factors. RESULTS:
      Licofelone dose dependently inhibited the IL1beta stimulated production and
      expression of MMP-13. NS-398 and BayX-1005 had very little effect. Licofelone
      also inhibited MMP-13 transcription on each of the promoter constructs used. The
      licofelone inhibition was comparable to that obtained with dexamethasone.
      Licofelone had no effect on phosphorylated p44/42 or JNK1/2; however, it
      decreased phosphorylated c-jun and inhibited phosphorylated p38, CREB, and AP-1
      activity. CONCLUSIONS: Licofelone inhibited MMP-13 production under
      proinflammatory conditions on human osteoarthritis chondrocytes, through
      inhibition of the p38/AP-1 pathway and the transcription factor CREB. This may
      explain some of the mechanisms whereby licofelone exerts its positive effect on
      osteoarthritic changes.

PMID- 15498797
TI  - Primary Sjogren's syndrome: new clinical and therapeutic concepts.
AB  - Sicca features are the central clinical manifestations of Sjogren's syndrome
      (SS), but recent studies have confirmed that primary SS has a systemic
      expression, including extraglandular manifestations. Patients with a
      predominantly extraepithelial expression should be managed differently from
      patients with predominantly periepithelial or sicca limited disease. In coming
      years treatment will be based on muscarinic agonists for sicca features and
      immunosuppressive/biological agents for extraglandular features.

PMID- 15498799
TI  - The lipid-activated two-pore domain K+ channel TREK-1 is resistant to hypoxia:
      implication for ischaemic neuroprotection.
AB  - TREK-1 is a member of the two-pore domain potassium (K(2P)) channel family that
      is mechano-, heat, pH, voltage and lipid sensitive. It is highly expressed in the
      central nervous system and probably encodes one of the previously described
      arachidonic acid-activated K(+) channels. Polyunsaturated fatty acids and
      lysophospholipids protect the brain against global ischaemia. Since both lipids
      are openers of TREK-1, it has been suggested that this K(2P) channel is directly
      involved in neuroprotection. Recently, however, this view has been challenged by
      a report claiming that TREK-1 and its activation by arachidonic acid is inhibited
      by hypoxia. In the present study, we demonstrate that the bubbling of saline with
      gases results in the loss of arachidonic acid from solution. Using experimental
      conditions which obviate this experimental artefact we demonstrate that TREK-1 is
      resistant to hypoxia and is strongly activated by arachidonic acid even at low
      P(O(2)) (< 4 Torr). Furthermore, hypoxia fails to affect basal as well as 2,4,6
      trinitrophenol- and acid-stimulated TREK-1 currents. These data are supportive
      for a possible role of TREK-1 in ischaemic neuroprotection and in cell signalling
      via arachidonic acid.

PMID- 15498798
TI  - Expression and regulation of cryopyrin and related proteins in rheumatoid
      arthritis synovium.
AB  - BACKGROUND: Rheumatoid arthritis (RA) synovium is characterised by enhanced NF
      kappaB activity and proinflammatory cytokines. Cryopyrin (CIAS-1, NALP-3, PYPAF
      1) has been shown to regulate NF-kappaB and caspase-1 activation. OBJECTIVE: To
      study the expression of cryopyrin, its effector molecule ASC, and its putative
      antagonist pyrin in RA and osteoarthritis (OA) synovium, and the main two
      cellular constituents of synovial lining, cultured fibroblast-like synoviocytes
      (FLS) and macrophages. METHODS: FLS and macrophages were cultured in the presence
      of inflammatory mediators. Real time polymerase chain reaction was used to
      quantify message levels in synovial biopsy specimens and cells. In situ
      hybridisation was employed to localise expression of cryopyrin mRNA. RESULTS:
      Cryopyrin mRNA was raised in RA synovium and detected in both lining and
      sublining regions. FLS from RA and OA tissue expressed low baseline levels of
      cryopyrin transcripts that were induced by tumour necrosis factor alpha
      (TNFalpha). In contrast, macrophages differentiated in vitro expressed relatively
      high cryopyrin levels, which were further induced by TNFalpha, but not by
      interleukin 1beta. ASC mRNA levels were comparable in RA and OA tissue, FLS, and
      macrophages, and were depressed by TNFalpha in macrophages. Pyrin expression was
      higher in RA synovium than in OA tissue, and virtually undetectable in FLS but
      high in macrophages where it was unchanged by TNFalpha treatment. CONCLUSION:
      These results suggest that enhanced cryopyrin levels in RA synovium are due to a
      greater numbers of tissue macrophages, and demonstrate transcriptional regulation
      of cryopyrin in a chronic inflammatory disease.

PMID- 15498800
TI  - Slc26a6: a cardiac chloride-hydroxyl exchanger and predominant chloride
      bicarbonate exchanger of the mouse heart.
AB  - Bicarbonate facilitate more than 50% of pH recovery in the acidotic myocardium,
      and have roles in cardiac hypertrophy and steady-state pH regulation. To
      determine which bicarbonate transporters are responsible for this activity, we
      measured the expression levels of all known HCO3(-)-anion exchange proteins in
      mouse heart, by quantitative real time RT-PCR. Bicarbonate-anion exchangers are
      members of either the SLC4A or the SLC26A gene families. In neonatal and adult
      myocardium, AE1 (Slc4a1), AE2 (Slc4a2), AE3 (Slc4a3) (AE3fl and AE3c variants),
      Slc26a3 and Slc26a6 were expressed. Adult hearts expressed Slc26a3 and Slc4a1-3
      mRNAs at similar levels, while Slc26a6 mRNA was about seven-fold higher than AE3,
      which was more abundant than any other. Immunohistochemistry revealed that
      Slc26a6 and AE3 are present in the plasma membrane of ventricular myocytes.
      Slc26a6 expression levels were higher in ventricle than atrium, whereas AE3 was
      detected only in ventricle. Cl(-)-HCO(3)(-) and Cl(-)-OH(-) exchange activity of
      SLC26A6 and AE3 were investigated in transfected HEK293 cells, using
      intracellular fluorescence measurements of 2',7'-bis (2-carboxyethyl)-5(6)
      carboxyfluorescein (BCECF), to monitor intracellular pH (pH(i)). Rates of pH(i)
      change were measured under HCO3(-)-containing (Cl(-)-HCO(3)(-)) or nominally
      HCO3(-)-free (Cl(-)-OH(-)) conditions. HCO3(-) fluxes were similar for cells
      expressing AE3fl, SLC26A6 or Slc26a3, suggesting that they have similar transport
      activity. However, only SLC26A6 and Slc26a3 functioned as Cl(-)-OH(-) exchangers.
      Activation of alpha-adrenergic receptors, which stimulates protein kinase C,
      inhibited SLC26A6 Cl(-)-HCO(3)(-) exchange activity. We conclude that Slc26a6 is
      the predominant Cl(-)-HCO(3)(-) and Cl(-)-OH(-) exchanger of the myocardium and
      that Slc26a6 is negatively regulated upon alpha-adrenergic stimulation.

PMID- 15498801
TI  - Stratum oriens horizontal interneurone diversity and hippocampal network
      dynamics.
AB  - In this last decade, the combination of differential interference contrast
      infrared video technology and patch-clamp techniques applied to slices in vitro
      has allowed the routine electrophysiological recording of visually identified
      central neurones. This has opened the way to the possibility of preselecting
      GABAergic interneurones of the hippocampus on the basis of some peculiar
      morphological characteristics. In particular, stratum oriens 'horizontal'
      interneurones are easily recognizable in living hippocampal slices because of
      their location and bipolar/bitufted appearance. Thus, this class of cells has
      rapidly risen as one of the most studied in the entire hippocampus. In this
      review, I will try to assemble the vast electrophysiological knowledge on these
      interneurones into a more focused picture, which is relevant for network activity
      in vitro and in vivo.

PMID- 15498802
TI  - The combined effects of exercise and food intake on adipose tissue and splanchnic
      metabolism.
AB  - Seven young, healthy male subjects were each studied in two separate experiments.
      (1) Subjects exercised for 60 min at 55% of peak oxygen consumption in the fasted
      state ending 30 min before a meal (60% of energy as carbohydrate, and 20% of
      energy as lipid and protein each) comprising 25% of the total daily energy
      intake, and were then studied for another 150 min postprandially during rest (E-
      >M). (2) One hour after a similar meal, subjects exercised for 60 min and were
      then studied for another 180 min postexercise during rest (M-->E). Regional
      adipose tissue and splanchnic tissue metabolism were measured by Fick's
      Principle. Food intake before exercise reduced whole-body lipid combustion during
      exercise to about 50% of the combustion rate found during exercise in the fasted
      state. The increase in subcutaneous, abdominal adipose tissue lipolysis during
      exercise was not influenced by preexercise food intake, while the fatty acid
      mobilization was increased by only 1.5-fold during postprandial exercise compared
      to a fourfold increase during exercise in the fasted state. During exercise,
      catecholamine concentrations increased similarly in the fasted and the
      postprandial state, while the insulin concentration was twofold higher
      postprandially. These results indicate that the increase in catecholamine
      concentrations during exercise is a more important determinant of the adipose
      tissue lipolytic rate than the decrease in insulin concentration. Furthermore,
      food intake either 30 min after or 1 h before exercise prevents the postexercise
      increase in adipose tissue glycerol and fatty acid release which normally takes
      place in fasting subjects at least up to 2.5 h postprandially. Postprandial
      exercise led to a faster increase in postprandial lipaemia. This could not be
      accounted for by changes in the regional splanchnic tissue or adipose tissue
      triacylglycerol metabolism. Exercise was able to increase hepatic glucose
      production irrespective of food intake before exercise. It is concluded that
      exercise performed in the fasted state shortly before a meal leads to a more
      favourable lipid metabolism during and after exercise than exercise performed
      shortly after a meal.

PMID- 15498803
TI  - The 'window' T-type calcium current in brain dynamics of different behavioural
      states.
AB  - All three forms of recombinant low voltage-activated T-type Ca(2)(+) channels
      (Ca(v)3.1, Ca(v)3.2 and Ca(v)3.3) exhibit a small, though clearly evident, window
      T-type Ca(2)(+) current (I(Twindow)) which is also present in native channels
      from different neuronal types. In thalamocortical (TC) and nucleus reticularis
      thalami (NRT) neurones, and possibly in neocortical cells, an I(Twindow)-mediated
      bistability is the key cellular mechanism underlying the expression of the slow
      (< 1 Hz) sleep oscillation, one of the fundamental EEG rhythms of non-REM sleep.
      As the I(Twindow)-mediated bistability may also represent one of the cellular
      mechanisms underlying the expression of high frequency burst firing in awake
      conditions, I(Twindow) is of critical importance in neuronal population dynamics
      associated with different behavioural states.

PMID- 15498805
TI  - Voltage-dependent calcium entry underlies propagation of slow waves in canine
      gastric antrum.
AB  - Electrical slow waves in gastrointestinal (GI) muscles are generated by
      interstitial cells of Cajal (ICC), and these events actively propagate through
      networks of ICC within the walls of GI organs. The mechanism by which
      spontaneously active pacemaker sites throughout ICC networks are entrained to
      produce orderly propagation of slow waves is unresolved. A three-chambered
      partition bath was used to test the effects of agents that affect metabolism,
      membrane potential and voltage-dependent Ca(2+) entry on slow wave propagation in
      canine antral smooth muscle strips. Slow waves evoked by electrical field
      stimulation actively propagated from end to end of antral muscle strips with a
      constant latency between two points of recording. When the central chamber of the
      bath was perfused with low-temperature solutions, mitochondrial inhibitors,
      reduced extracellular Ca(2+) or blockers of voltage-dependent Ca(2+) channels,
      active propagation failed. Depolarization or hyperpolarization of the tissue
      within the central chamber also blocked propagation. Blockade of propagation by
      reduced extracellular Ca(2+) and inhibitors of dihydropyridine-resistant Ca(2+)
      channels suggests that voltage-dependent Ca(2+) entry may be the 'entrainment
      factor' that facilitates active propagation of slow waves in the gastric antrum.

PMID- 15498804
TI  - Background synaptic activity in rat entorhinal cortical neurones: differential
      control of transmitter release by presynaptic receptors.
AB  - The entorhinal cortex (EC) is a key brain area controlling both hippocampal input
      and output via neurones in layer II and layer V, respectively. It is also a
      pivotal area in the generation and propagation of epilepsies involving the
      temporal lobe. We have previously shown that within the network of the EC,
      neurones in layer V are subject to powerful synaptic excitation but weak
      inhibition, whereas the reverse is true in layer II. The deep layers are also
      highly susceptible to acutely provoked epileptogenesis. Considerable evidence now
      points to a role of spontaneous background synaptic activity in control of
      neuronal, and hence network, excitability. In the present article we describe
      results of studies where we have compared background release of the excitatory
      transmitter, glutamate, and the inhibitory transmitter, GABA, in the two layers,
      the role of this background release in the balance of excitability, and its
      control by presynaptic auto- and heteroreceptors on presynaptic terminals.

PMID- 15498806
TI  - Transmural expression of transient outward potassium current subunits in normal
      and failing canine and human hearts.
AB  - The transient outward current (I(to)), an important contributor to transmural
      electrophysiological heterogeneity, is significantly remodelled in congestive
      heart failure (CHF). The molecular bases of transmural I(to) gradients and CHF
      dependent ionic remodelling are incompletely understood. To elucidate these
      issues, we studied mRNA and protein expression of Kv4.3 and KChIP2, the principal
      alpha and beta subunits believed to form I(to), in epicardial and endocardial
      tissues and in isolated cardiomyocytes from control dogs and dogs with CHF
      induced by 240 beats min(-1) ventricular tachypacing. CHF decreased I(to) density
      in both epicardium and endocardium (by 73 and 55% at +60 mV, respectively),
      without a significant change in relative current density (endocardium/epicardium
      0.11 control, 0.17 CHF). There were transmural gradients in mRNA expression of
      both Kv4.3 (endocardium/epicardium ratio 0.3 under control conditions) and KChIP2
      (endocardium/epicardium ratio 0.2 control), which remained in the presence of CHF
      (Kv4.3 endocardium/epicardium ratio 0.4; KChIP2 0.4). There were qualitatively
      similar protein expression gradients in human and canine cardiac tissues and
      isolated canine cardiomyocytes; however, the KChIP2 gradient was only detectable
      with a highly selective monoclonal antibody and closely approximated the I(to)
      density gradient. Kv4.3 mRNA expression was reduced by CHF, but KChIP2 mRNA was
      not significantly changed. CHF decreased Kv4.3 protein expression in canine
      cardiac tissues and cardiomyocytes, as well as in terminally failing human heart
      tissue samples, but KChIP2 protein was not down-regulated in any of the
      corresponding sample sets. We conclude that both Kv4.3 and KChIP2 may contribute
      to epicardial-endocardial gradients in I(to), and that I(to) down-regulation in
      human and canine CHF appears due primarily to changes in Kv4.3.

PMID- 15498807
TI  - High triacylglycerol turnover rate in human skeletal muscle.
AB  - In the present study we investigated the relationship between plasma fatty acids
      (FA) and intramuscular triacylglycerol (IMTAG) kinetics of healthy volunteers.
      With this aim [U-(13)C]-palmitate was infused for 10 h and FA kinetics determined
      across the leg. In addition, the rate of FA incorporation into IMTAG in vastus
      lateralis muscle was determined during two consecutive 4-h periods (2-6 h and 6
      10 h). Fifty to sixty per cent of the FA taken up from the circulation were
      esterified into IMTAG, whereas 32 and 42% were oxidized between 2-6 and 6-10 h,
      respectively. IMTAG fractional synthesis rate was 3.4 +/- 0.8% h(-1) and did not
      change between the two 4- h periods, despite an increase in arterial FA
      concentration (34%, P < 0.01). IMTAG concentration was also unchanged, implying
      that the IMTAG fractional synthesis rate was balanced by an equal rate of
      breakdown. FA oxidation increased over time, which could be due to the observed
      decline in plasma insulin concentration (-74%, P < 0.01). In conclusion, a
      substantial fraction of the fatty acids entering skeletal muscle in post
      absorptive healthy individuals is esterified into IMTAG, due to its high turnover
      rate (29 h pool(-1)). An increase in FA level, as a consequence of short-term
      fasting, does not seem to increase IMTAG synthesis rate and pool size.

PMID- 15498808
TI  - Specific pattern of ionic channel gene expression associated with pacemaker
      activity in the mouse heart.
AB  - Even though sequencing of the mammalian genome has led to the discovery of a
      large number of ionic channel genes, identification of the molecular determinants
      of cellular electrical properties in different regions of the heart has been
      rarely obtained. We developed a high-throughput approach capable of
      simultaneously assessing the expression pattern of ionic channel repertoires from
      different regions of the mouse heart. By using large-scale real-time RT-PCR, we
      have profiled 71 channels and related genes in the sinoatrial node (SAN),
      atrioventricular node (AVN), the atria (A) and ventricles (V). Hearts from 30
      adult male C57BL/6 mice were microdissected and RNA was isolated from six pools
      of five mice each. TaqMan data were analysed using the threshold cycle (C(t))
      relative quantification method. Cross-contamination of each region was checked
      with expression of the atrial and ventricular myosin light chains. Two-way
      hierarchical clustering analysis of the 71 genes successfully classified the six
      pools from the four distinct regions. In comparison with the A, the SAN and AVN
      were characterized by higher expression of Nav beta 1, Nav beta 3, Cav1.3, Cav3.1
      and Cav alpha 2 delta 2, and lower expression of Kv4.2, Cx40, Cx43 and Kir3.1. In
      addition, the SAN was characterized by higher expression of HCN1 and HCN4, and
      lower expression of RYR2, Kir6.2, Cav beta 2 and Cav gamma 4. The AVN was
      characterized by higher expression of Nav1.1, Nav1.7, Kv1.6, Kvbeta1, MinK and
      Cav gamma 7. Other gene expression profiles discriminate between the ventricular
      and the atrial myocardium. The present study provides the first genome-scale
      regional ionic channel expression profile in the mouse heart.

PMID- 15498809
TI  - Augmented sympathetic vasoconstriction in exercising forearms of postmenopausal
      women is reversed by oestrogen therapy.
AB  - Sympathetic vasoconstriction is normally attenuated in exercising muscles of
      young men and women. Recent evidence indicates that such modulation, termed
      functional sympatholysis, may be impaired in older men. Whether a similar
      impairment occurs in older women, and what role oestrogen deficiency might play
      in this impairment, are not known. Based on the strong positive correlation
      between circulating oestrogen levels and functional sympatholysis previously
      reported in female rats, we hypothesized that sympatholysis would be impaired in
      oestrogen-deficient postmenopausal women, and that this impairment would be
      reversed by oestrogen replacement. To test these hypotheses, we measured
      vasoconstrictor responses in the forearms of pre- and postmenopausal women using
      near infrared spectroscopy to detect decreases in muscle oxygenation in response
      to reflex activation of sympathetic nerves evoked by lower body negative pressure
      (LBNP). In eight premenopausal women, LBNP decreased muscle oxygenation by 20 +/-
      1% in resting forearm, but only by 3 +/- 2% in exercising forearm (P < 0.05). In
      contrast, in eight postmenopausal women, LBNP decreased muscle oxygenation by 15
      +/- 3% in resting forearm, and by 12 +/- 4% in exercising forearm (P > 0.05).
      After 1 month of transdermal oestradiol replacement in these women, the normal
      effect of exercise to blunt sympathetic vasoconstriction was restored (rest, -19
      +/- 3%; exercise, -2 +/- 3%; P < 0.05). These data indicate that functional
      sympatholysis is impaired in oestrogen-deficient postmenopausal women. The effect
      of short-term unopposed oestrogen replacement to correct this impairment
      implicates a role for oestrogen in the sympathetic neural control of muscle
      haemodynamics during exercise.

PMID- 15498810
TI  - Persistent changes in the intrinsic excitability of rat deep cerebellar nuclear
      neurones induced by EPSP or IPSP bursts.
AB  - The deep cerebellar nuclei (DCN) are the major output of the cerebellum, and have
      been proposed as a site of memory storage for certain forms of motor learning.
      Microelectrode and whole-cell patch recordings were performed on DCN neurones in
      acute slices of juvenile rat cerebellum. DCN neurones display tonic and bursting
      basal firing patterns. In tonically firing neurones, a stimulus consisting of
      EPSP bursts produced a brief increase in dendritic Ca(2+) concentration and a
      persistent increase in the number of spikes elicited by a depolarizing test
      pulse, along with a decrease in spike threshold. In intrinsically bursting DCN
      neurones, EPSP bursts induced an increase in the number of depolarization-evoked
      spikes in some neurones, but in others produced a change to a more tonic firing
      pattern. Application of IPSP bursts evoked a large number of rebound spikes and
      an associated dendritic Ca(2+) transient, which also produced a persistent
      increase in the number of spikes elicited by a test pulse. Intracellular
      perfusion of the Ca(2+) chelator BAPTA prevented the increase in intrinsic
      excitability. Thus, rapid changes in intrinsic excitability in the DCN may be
      driven by bursts of both EPSPs and IPSPs, and may result in persistent changes to
      both firing frequency and pattern.

PMID- 15498811
TI  - Prostaglandins participate in the late phase of the vascular response to
      acetylcholine iontophoresis in humans.
AB  - The participation of prostaglandins (PGs) in the cutaneous vasodilatation to
      acetylcholine (ACh) applied via iontophoresis is under debate. Using laser
      Doppler flowmetry, we studied the long lasting effect (20 min) of iontophoretic
      application (30 s; 0.1 mA) of ACh on the human forearm. Experiments were repeated
      (1) using deionized water instead of ACh to test the effect of current
      application, (2) after scopolamine treatment to inhibit muscarinic cholinergic
      receptors, and (3) 2 h, 3 days and 10 days following inhibition of PG synthesis
      with aspirin or a placebo control. Cutaneous vascular conductance (CVC) was
      calculated at rest (CVC(rest)), at peak vasodilatation in the first 5 min
      following ACh iontophoresis (CVC(peak)), and 20 min after iontophoresis
      (CVC(20)). The minimal CVC (CVC(min)) following iontophoresis was also
      determined. Cutaneous response to ACh displayed a biphasic pattern with an early
      and transient peak (CVC(peak): 62 +/- 8% of the maximal CVC induced by local
      heating (MVC)) followed by a long lasting slower vasodilatation (CVC(min): 44 +/-
      6; CVC(20): 56 +/- 5%MVC). The current itself had no major effect. Scopolamine
      almost abolished both phases. The long lasting phase was aspirin sensitive but
      not the transient phase. At hour 2 post-aspirin, CVC(peak) was 61 +/- 10,
      CVC(min) 26 +/- 6 and CVC(20) 29 +/- 6%MVC. At day 3, CVC(peak) was 53 +/- 9,
      CVC(min) 22 +/- 3 and CVC(20) 25 +/- 4%MVC. At day 10, CVC(peak) was 67 +/- 10,
      CVC(min) 47 +/- 7 and CVC(20) 50 +/- 8%MVC. Placebo had no effect. We conclude
      that PGs participate in the vasodilator response following ACh iontophoresis.
      Previous non-steroidal anti-inflammatory drug treatments must be taken into
      account when studying the effect of ACh iontophoresis.

PMID- 15498812
TI  - Acetyl group availability influences phosphocreatine degradation even during
      intense muscle contraction.
AB  - We previously established that activation of the pyruvate dehydrogenase complex
      (PDC) using dichloroacetate (DCA) reduced the reliance on substrate-level
      phosphorylation (SLP) at the onset of exercise, with normal and reduced blood
      flow. PDC activation also reduced fatigue development during contraction with
      reduced blood flow. Since these observations, several studies have re-evaluated
      our observations. One study demonstrated a performance benefit without a
      reduction in SLP, raising a question mark over PDC's role in the regulation of
      ATP regeneration and our interpretation of fatigue mechanisms. Using a model of
      muscle contraction similar to the conflicting study (i.e. tetanic rather than
      twitch stimulation), we re-examined this question. Using canine skeletal muscle,
      one group was infused with saline while the other was pretreated with 300 mg (kg
      body mass)(-1) DCA. Muscle biopsies were taken at rest, peak tension (1 min) and
      after 6 min of tetanic electrical stimulation (75 ms on-925 ms off per second)
      and blood flow was limited to 25% of normal values observed during contraction.
      DCA reduced phosphocreatine (PCr) degradation by 40% during the first minute of
      contraction, but did not prevent the almost complete depletion of PCr stores at 6
      min, while muscle fatigue did not differ between the two groups. During
      intermittent tetanic stimulation PCr degradation was 75% greater than with our
      previous 3 Hz twitch contraction protocol, despite a similar rate of oxygen
      consumption at 6 min. Thus, in the present study enhanced acetyl group
      availability altered the time course of PCr utilization but did not prevent the
      decline towards depletion. Consistent with our earlier conclusions, DCA
      pretreatment reduces muscle fatigue only when SLP is attenuated. The present
      study and our met-analysis indicates that enhanced acetyl group availability
      results in a readily measurable reduction in SLP when the initial rate of PCr
      utilization is approximately 1 mmol (kg dry mass)(-1) s(-1) or less (depending on
      intrinsic mitochondrial capacity). When measured early during an uninterrupted
      period of muscle contraction, acetyl group availability is likely to influence
      SLP under any condition where mitochondria are responsible for a significant
      proportion of ATP regeneration.

PMID- 15498813
TI  - Induction of striatal long-term synaptic depression by moderate frequency
      activation of cortical afferents in rat.
AB  - The striatum regulates motor output, and it is thought that changes in the
      synaptic efficacy of inputs to the striatum contribute to motor learning and
      habit formation. Previously, several laboratories have observed that brief high
      frequency stimulation (HFS) of cortical afferents innervating the dorsolateral
      striatum induces a long-term decrease in synaptic efficacy called long-term
      depression (LTD). We recently showed that HFS-induced striatal LTD requires
      retrograde signalling involving postsynaptic release of endocannabinoids and
      activation of presynaptic CB1 cannabinoid receptors. In the present study we have
      employed whole-cell recording in brain slices to examine a new form of LTD at
      corticostriatal synapses that can be induced by a 10 Hz, 5 min train. The
      decrease in synaptic efficacy is associated with a decrease in presynaptic
      release probability, as demonstrated by a decrease in frequency but not amplitude
      of spontaneous excitatory postsynaptic currents (sEPSCs) and an increase in the
      paired pulse ratio (PPR). This form of LTD is blocked by antagonists for CB1 and
      D2 dopamine receptors and impaired by blockers of L-type calcium channels.
      However, 10 Hz-induced LTD does not depend on postsynaptic depolarization, unlike
      HFS-induced LTD. Furthermore, this new form of LTD is not prevented by treatments
      known to block HFS-induced LTD, including antagonism of metabotropic glutamate
      receptors (mGluRs), chelation of postsynaptic calcium, or intracellular
      application of an anandamide membrane transport inhibitor (VDM11). From these
      findings it is not clear that the endocannabinoid responsible for this form of
      LTD acts in a retrograde fashion, and the cellular source of endocannabinoid
      necessary for 10 Hz-induced LTD is as yet unknown. Our results demonstrate that a
      prolonged moderate frequency train induces cannabinoid-dependent LTD, further
      supporting the idea that endocannabinoids play a prominent role in the regulation
      of long-lasting changes in striatal output.

PMID- 15498814
TI  - Expression of the largest CD97 and EMR2 isoforms on leukocytes facilitates a
      specific interaction with chondroitin sulfate on B cells.
AB  - The EGF-TM7 receptors CD97 and EMR2 are heptahelical molecules predominantly
      expressed on leukocytes. A characteristic of these receptors is their ability to
      interact with cellular ligands via the N-terminal epidermal growth factor (EGF)
      like domains. The first two EGF domains of CD97 (but not EMR2) bind CD55 (decay
      accelerating factor), while the fourth EGF domain of both CD97 and EMR2 interacts
      with the glycosaminoglycan chondroitin sulfate (CS). Using fluorescent beads
      coated with soluble recombinant CD97 and EMR2 protein, and isoform-specific
      monoclonal antibodies, we have determined the cellular and molecular
      characteristics of the interaction with CS. The fourth EGF domain of CD97 and
      EMR2 is expressed on activated lymphocytes and myeloid cells, whereas the ligand
      is specifically found on B cells within the peripheral blood. The interaction
      between CD97/EMR2 and CS may therefore play a role in the interaction of
      activated T cells, dendritic cells, and macrophages with B cells.

PMID- 15498815
TI  - T cell contact-mediated activation of respiratory burst in human
      polymorphonuclear leukocytes is inhibited by high-density lipoproteins and
      involves CD18.
AB  - Polymorphonuclear neutrophils (PMN) are recruited to sites of inflammation, where
      they are in close vicinity with other immune cell types. The present study
      demonstrates that direct cell-cell contact with stimulated T cells activates PMN
      respiratory burst. To discard interferences with soluble products, membranes
      isolated from human T lymphocytes (msT) or the monocytic cell line HUT-78 (msHUT)
      were used to mimic cellular contact. msT and msHUT induced a dose-dependent
      production of radical oxygen species (ROS) in PMN, as detected by
      chemiluminescence. Similar results were obtained with fixed, stimulated T cells,
      confirming that ROS production was a result of cell-surface molecules and not to
      soluble products of T cells. ROS production was mainly intracellular, suggesting
      that ROS may take part in intracellular processes. High-density lipoproteins
      (HDL), which had previously been shown to inhibit T cell contact-induced cytokine
      production in monocyte-macrophages, potently reduced ROS production induced in
      PMN upon contact with stimulated T cells. This supports the emerging role of HDL
      as immunomodulators in inflammatory diseases. Furthermore, monoclonal antibodies
      to CD18 inhibited 60% of the PMN respiratory burst induced by msT, suggesting
      that CD18 contributed to PMN activation. The present results emphasize the
      importance of direct cell-cell contact with stimulated T cells in inflammatory
      processes.

PMID- 15498816
TI  - Human Vgamma9/Vdelta2 effector memory T cells express the killer cell lectin-like
      receptor G1 (KLRG1).
AB  - The killer cell lectin-like receptor G1 (KLRG1) is expressed in natural killer
      (NK) cells and effector memory alphabeta T cells. Gammadelta T cells represent an
      unconventional lymphocyte population that shares characteristics of NK cells and
      T cells and links innate and adaptive immunity. Vgamma9/Vdelta2 T cells comprise
      the majority of peripheral human gammadelta T cells and respond to the microbial
      metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP). Here, we
      demonstrate that KLRG1 is expressed in a significant proportion of
      Vgamma9/Vdelta2 T cells in cord blood and in the majority of peripheral
      Vgamma9/Vdelta2 T cells from adult donors. KLRG1+ Vgamma9/Vdelta2 T cells
      displayed an effector memory phenotype, as KLRG1 was expressed mainly in
      Vgamma9/Vdelta2 T cells lacking CD27, CD45RA, CD62L, and CC chemokine receptor 7
      (CCR7). Unlike alphabeta T cells, where possession of KLRG1 identified effector
      memory cells with impaired proliferative capacity, KLRG1+ Vgamma9/Vdelta2 T cells
      were able to proliferate vigorously upon stimulation with HMB-PP in the presence
      of interleukin-2. Moreover, KLRG1 ligation on Vgamma9/Vdelta2 T cells by
      antibodies did not inhibit HMB-PP-induced proliferation and cytokine production
      nor cytolysis of Daudi cells.

PMID- 15498817
TI  - Diminished CD4+ T cell surface CCR5 expression in alcoholic patients.
AB  - AIMS: The C-C chemokine receptors, particularly the CCR5, appeared to play an
      important role in T cell-mediated inflammatory reactions. The aim of our study
      was to assess the impact of chronic alcohol consumption on the in vivo CCR5
      expression. METHODS: Fourteen alcoholic men hospitalized for a detoxification
      programme were prospectively included and compared with 49 age-matched controls.
      RESULTS: The CD4(+) T cell surface CCR5 densities were drastically lower in
      alcoholic patients [mean, 5319 molecules/cell; 95% confidence interval (CI) 4477
      6162] as compared with CCR5 densities of the controls (10 944 molecules/cell [CI
      9929-11959]; P < 10(-4)). CONCLUSIONS: Chronic alcohol consumption is associated
      with a significant decrease of CCR5 expression, which could favour Th1/Th2
      imbalance.

PMID- 15498818
TI  - Low voltage-activated calcium channels in vascular smooth muscle: T-type channels
      and AVP-stimulated calcium spiking.
AB  - An important path of extracellular calcium influx in vascular smooth muscle (VSM)
      cells is through voltage-activated Ca2+ channels of the plasma membrane. Both
      high (HVA)- and low (LVA)-voltage-activated Ca2+ currents are present in VSM
      cells, yet little is known about the relevance of the LVA T-type channels. In
      this report, we provide molecular evidence for T-type Ca2+ channels in rat
      arterial VSM and characterize endogenous LVA Ca2+ currents in the aortic smooth
      muscle-derived cell line A7r5. AVP is a vasoconstrictor hormone that, at
      physiological concentrations, stimulates Ca2+ oscillations (spiking) in monolayer
      cultures of A7r5 cells. The present study investigated the role of T-type Ca2+
      channels in this response with a combination of pharmacological and molecular
      approaches. We demonstrate that AVP-stimulated Ca2+ spiking can be abolished by
      mibefradil at low concentrations (<1 microM) that should not inhibit L-type
      currents. Infection of A7r5 cells with an adenovirus containing the Cav3.2 T-type
      channel resulted in robust LVA Ca2+ currents but did not alter the AVP-stimulated
      Ca2+ spiking response. Together these data suggest that T-type Ca2+ channels are
      necessary for the onset of AVP-stimulated calcium oscillations; however, LVA Ca2+
      entry through these channels is not limiting for repetitive Ca2+ spiking observed
      in A7r5 cells.

PMID- 15498819
TI  - Dynamic cerebral autoregulation during exhaustive exercise in humans.
AB  - We investigated whether dynamic cerebral autoregulation is affected by exhaustive
      exercise using transfer-function gain and phase shift between oscillations in
      mean arterial pressure (MAP) and middle cerebral artery (MCA) mean blood flow
      velocity (V(mean)). Seven subjects were instrumented with a brachial artery
      catheter for measurement of MAP and determination of arterial Pco(2) (Pa(CO(2)))
      while jugular venous oxygen saturation (Sv(O(2))) was determined to assess
      changes in whole brain blood flow. After a 10-min resting period, the subjects
      performed dynamic leg-cycle ergometry at 168 +/- 5 W (mean +/- SE) that was
      continued to exhaustion with a group average time of 26.8 +/- 5.8 min. Despite no
      significant change in MAP during exercise, MCA V(mean) decreased from 70.2 +/-
      3.6 to 57.4 +/- 5.4 cm/s, Sv(O(2)) decreased from 68 +/- 1 to 58 +/- 2% at
      exhaustion, and both correlated to Pa(CO(2)) (5.5 +/- 0.2 to 3.9 +/- 0.2 kPa; r =
      0.47; P = 0.04 and r = 0.74; P < 0.001, respectively). An effect on brain
      metabolism was indicated by a decrease in the cerebral metabolic ratio of O(2) to
      [glucose + one-half lactate] from 5.6 to 3.8 (P < 0.05). At the same time, the
      normalized low-frequency gain between MAP and MCA V(mean) was increased (P <
      0.05), whereas the phase shift tended to decrease. These findings suggest that
      dynamic cerebral autoregulation was impaired by exhaustive exercise despite a
      hyperventilation-induced reduction in Pa(CO(2)).

PMID- 15498820
TI  - Angiogenic protection from focal ischemia with angiotensin II type 1 receptor
      blockade in the rat.
AB  - Angiogenesis within an ischemic region of the brain may increase tissue viability
      and act to limit the extent of an infarct. The ANG II pathway can both stimulate
      and inhibit angiogenesis depending on the tissue and the activated receptors.
      Previous work showed that 2-wk losartan administration (ANG II type 1 receptor
      blockade) initiates a significant cerebral angiogenic response. We hypothesized
      that administration of losartan in the drinking water of rats for 2 wk before
      initiation of focal ischemia would decrease the extent of the resulting infarct.
      Adult male Sprague-Dawley rats were given losartan (50 mg/day) in drinking water
      for 2 wk before initiation of cerebral focal ischemia produced by cauterization
      of cortical surface vessels. Controls received normal drinking water. In control
      animals, three main vessels feeding the whisker barrel cortex were cauterized,
      resulting in cessation of blood flow. The same protocol was followed for losartan
      treated animals but did not result in cessation of blood flow in the whisker
      barrel cortex. Another group of losartan-treated animals received between 8 and
      14 cauterizations of surface vessels feeding the whisker barrel cortex, and
      cessation of blood flow was verified. Rats were killed 72 h after surgery.
      Morphological examination revealed angiogenesis, maintained vascular delivery,
      and significantly decreased infarct size in losartan-treated animals compared
      with controls. These results demonstrate that pretreatment with losartan reduces
      infarct size after cerebral focal ischemia and support the hypothesis that
      cerebral angiogenesis may be one of the mechanisms responsible.

PMID- 15498821
TI  - Ligand-mediated decrease of thyroid hormone receptor-alpha1 in cardiomyocytes by
      proteosome-dependent degradation and altered mRNA stability.
AB  - Tri-iodo-L-thyronine (T3) is essential for maintaining normal cardiac contractile
      function by regulating transcription of numerous T3-responsive genes. Both
      hormone availability and relative amounts of nuclear thyroid hormone receptor
      isoforms (TRalpha1, TRbeta1) determine T3 effectiveness. Cultured neonatal rat
      ventricular myocytes grown in T3-depleted medium expressed predominantly TRalpha1
      protein, but within 4 h of T3 treatment, TRbeta1 protein increased significantly,
      whereas TRalpha1 was decreased by 46 +/- 5%. Using replication-defective
      adenoviruses to overexpress TRalpha1 in cardiomyocytes, we studied the mechanisms
      by which T3 mediated the decrease in TRalpha1 protein. Inhibitors of the
      proteosome pathway resulted in an accumulation of ubiquitylated TRalpha1 in the
      nucleus and prevented T3-induced degradation of ubiquitylated TRalpha1,
      suggesting that T3 induced proteosome-mediated degradation of TRalpha1; however,
      TR ubiquitylation was T3 independent. TRalpha1 transcriptional activity, measured
      using transient transfection of a thyroid hormone-responsive element (TRE)
      reporter plasmid, was T3 dose dependent and inversely proportional to nuclear
      TRalpha1 content, with 10 nM T3 having maximum effect. Quantitative RT-PCR showed
      that both endogenous and adenovirus-expressed TRalpha1 mRNAs were significantly
      decreased to 54 +/- 11 and 25 +/- 5%, respectively, within 4 h of T3 treatment.
      Measurements of TRalpha1 mRNA half-life in actinomycin D-treated cardiomyocytes
      showed that T3 treatment significantly decreased TRalpha1 mRNA half-life from 4 h
      to less than 2 h, whereas it had no effect of TRbeta1 mRNA half-life. These data
      support a role for both the proteosome degradation pathway and altered mRNA
      stability in T3-induced decrease of nuclear TRalpha1 in the cardiomyocyte and
      provide novel cellular targets for therapeutic development.

PMID- 15498822
TI  - fMLP-stimulated neutrophils increase endothelial [Ca2+]i and microvessel
      permeability in the absence of adhesion: role of reactive oxygen species.
AB  - Our previous study demonstrated that firm attachment of leukocytes to microvessel
      walls does not necessarily increase microvessel permeability (Am J Physiol Heart
      Circ Physiol 283: H2420-H2430, 2002). To further understand the mechanisms of the
      permeability increase associated with leukocyte accumulation during acute
      inflammation, we investigated the direct relation of reactive oxygen species
      (ROS) release during neutrophil respiratory burst to changes in microvessel
      permeability and endothelial intracellular Ca(2+) concentration ([Ca(2+)](i)) in
      intact microvessels. ROS release from activated neutrophils was quantified by
      measuring changes in chemiluminescence. When isolated rat neutrophils (2 x
      10(6)/ml) were exposed to formyl-Met-Leu-Phe-OH (fMLP, 10 microM),
      chemiluminescence transiently increased from 1.2 +/- 0.2 x 10(4) to a peak value
      of 6.7 +/- 1.0 x 10(4) cpm/min (n = 12). Correlatively, perfusing individual
      microvessels with fMLP-stimulated neutrophils in suspension (2 x 10(7)/ml)
      increased hydraulic conductivity (L(p)) to 3.7 +/- 0.4 times the control value (n
      = 5) and increased endothelial [Ca(2+)](i) from 84 +/- 7 nM to a mean peak value
      of 170 +/- 7 nM. In contrast, perfusing vessels with fMLP alone did not affect
      basal L(p). Application of antioxidant agents, superoxide dismutase, vitamin C,
      or an iron chelator, deferoxamine mesylate, attenuated ROS release in fMLP
      stimulated neutrophils and abolished increases in L(p). These results indicate
      that release of ROS from fMLP-stimulated neutrophils increases microvessel
      permeability and endothelial [Ca(2+)](i) independently from leukocyte adhesion
      and the migration process.

PMID- 15498823
TI  - Effect of sarcolemmal rupture on myocardial electrical impedance during oxygen
      deprivation.
AB  - Plasma membrane disruption is a characteristic feature of cell death induced by
      hypoxia or ischemia. Here, we investigated whether analysis of tissue electrical
      impedance allows detection of ongoing cell membrane rupture and necrotic cell
      death in hypoxic or ischemic myocardium. Twenty-eight isolated rat hearts were
      submitted to 5 h of ischemia (n = 8) or hypoxia (n = 20). Myocardial electrical
      impedance and lactate dehydrogenase (LDH) release were monitored. The time course
      of hypoxia-induced cell death was modified by altering pH (pH 7.4 or 6.4, 5 h) or
      by adding 3 or 10 mM glycine. Ischemia and hypoxia induced an increase in
      electrical impedance, followed by a plateau, and later a reduction. During
      hypoxia, LDH release started after a prolonged lapse of time (80.00 +/- 8.37 min
      at pH 7.4 and 122.50 +/- 11.82 min at pH 6.4). The onset of LDH release was
      followed by the onset of the late reduction in electrical impedance, and both
      were delayed by acidic pH (P < 0.05) and by glycine (P < 0.05). The times of
      onset of LDH release and of late electrical changes were significantly correlated
      (r = 0.752, P < 0.001). In separate experiments, induction of sarcolemmal rupture
      with Triton X-100 (n = 6) mimicked the late effects of ischemia or hypoxia on
      tissue impedance. The protective effects of glycine and acidosis on membrane
      disruption were confirmed (propidium iodide) in energy-deprived HL-1
      cardiomyocytes. These results describe for the first time a late fall in
      electrical impedance in myocardium submitted to prolonged oxygen deprivation and
      demonstrate that this fall allows detection of ongoing cell necrosis.

PMID- 15498824
TI  - Inhibition of cardiac fibroblast proliferation and myofibroblast differentiation
      by resveratrol.
AB  - Cardiac fibroblasts (CFs) regulate myocardial remodeling by proliferating,
      differentiating, and secreting extracellular matrix proteins. Prolonged
      activation of CFs leads to cardiac fibrosis and reduced myocardial contractile
      function. Resveratrol (RES) exhibits a number of cardioprotective properties;
      however, the possibility that this compound affects CF function has not been
      considered. The current study tests whether RES directly influences the growth
      and proliferation of CFs and differentiation to the hypersecretory myofibroblast
      phenotype. Pretreatment of CFs with RES (5-25 microM) inhibited basal and ANG II
      induced extracellular signal-regulated kinase (ERK) 1/2 and ERK kinase
      activation. This inhibition by RES reduced basal proliferation and blocked ANG II
      induced growth and proliferation of CFs in a concentration-dependent manner, as
      measured by [(3)H]leucine and [(3)H]thymidine incorporation, respectively. RES
      pretreatment attenuated ERK phosphorylation when CFs were stimulated with 0.2 nM
      epidermal growth factor (EGF), a concentration at which EGF-induced ERK
      activation over basal was similar to the phosphorylation induced by 100 nM ANG
      II. Akt phosphorylation in CFs was unaffected by treatment with either 100 nM ANG
      II or 25 microM RES. Pretreatment of CFs with RES also reduced both ANG II- and
      transforming growth factor-beta-induced CF differentiation to the myofibroblast
      phenotype, indicated by a reduction in alpha-smooth muscle actin expression and
      stress fiber organization in CFs. This study identifies RES as an anti-fibrotic
      agent in the myocardium by limiting CF proliferation and differentiation, two
      critical steps in the pathogenesis of cardiac fibrosis.

PMID- 15498825
TI  - Modest actomyosin energy conservation increases myocardial postischemic function.
AB  - We have proposed that pharmacological preconditioning, leading to PKC-epsilon
      activation, in hearts improves postischemic functional recovery through a
      decrease in actomyosin ATPase activity and subsequent ATP conservation. The
      purpose of the present study was to determine whether moderate PKC-independent
      decreases in actomyosin ATPase are sufficient to improve myocardial postischemic
      function. Rats were given propylthiouracil (PTU) for 8 days to induce a 25%
      increase in beta-myosin heavy chain with a 28% reduction in actomyosin ATPase
      activity. Recovery of postischemic left ventricular developed pressure (LVDP) was
      significantly higher in PTU-treated rat hearts subjected to 30 min of global
      ischemia than in control hearts: 57.9 +/- 6.2 vs. 32.6 +/- 5.1% of preischemic
      values. In addition, PTU-treated hearts exhibited a delayed onset of rigor
      contracture during ischemia and a higher global ATP content after ischemia. In
      the second part of our study, we demonstrated a lower maximal actomyosin ATPase
      and a higher global ATP content after ischemia in human troponin T (TnT)
      transgenic mouse hearts. In mouse hearts with and without a point mutation at
      F110I of human TnT, recovery of postischemic LVDP was 55.4 +/- 5.5 and 62.5 +/-
      14.5% compared with 20.0 +/- 2.9% in nontransgenic mouse hearts after 35 min of
      global ischemia. These results are consistent with the hypothesis that moderate
      decreases in actomyosin ATPase activity result in net ATP conservation that is
      sufficient to improve postischemic contractile function.

PMID- 15498826
TI  - Cardiac and renal effects of omapatrilat, a vasopeptidase inhibitor, in rats with
      experimental congestive heart failure.
AB  - Omapatrilat (OMP) is a novel mixed inhibitor of angiotensin-converting enzyme
      (ACE) and neutral endopeptidase 24.11 (NEP), the enzyme that metabolizes
      natriuretic peptides. Congestive heart failure (CHF) is characterized by
      excessive sodium retention, attributed to both an excessive effect of angiotensin
      II and diminished responsiveness to natriuretic peptides. In this study, we
      examined the acute and chronic renal and cardiac effects of OMP in rats with
      compensated [urinary sodium excretion (UNaV) > 1,200 microeq/day] and
      decompensated (UNaV < 100 microeq/day) CHF, induced by a surgical aortocaval
      fistula (ACF). Bolus injection of OMP (10 mg/kg) to sham controls produced
      significant diuretic and natriuretic responses [UNaV increased from 0.67 +/- 0.19
      to 3.27 +/- 1.35 microeq/min, P < 0.05; fractional sodium excretion (FENa)
      increased from 0.23 +/- 0.06 to 0.95 +/- 0.34%, P < 0.01] despite a significant
      decline in blood pressure (BP). Rats with compensated CHF displayed blunted
      diuresis and natriuresis to this dose of OMP but a significant decrease in BP.
      However, in rats with decompensated CHF, OMP induced significant natriuresis
      (FENa increased from 0.18 +/- 0.15 to 0.82 +/- 0.26%, P < 0.05) despite a further
      decrease in BP (from 90 +/- 9 to 71 +/- 6 mmHg, P < 0.01). Two weeks after ACF,
      the heart/body weight ratio was significantly greater in rats with CHF than
      controls (0.51 +/- 0.026 vs. 0.30 +/- 0.004%, P < 0.0001), and UNaV was
      significantly lower. Immediate or late (1 or 6 days after ACF) OMP treatment in
      the drinking water (140 mg/l) reduced cardiac hypertrophy to 0.41-0.43% (P <
      0.01) and induced natriuresis. These results suggest that OMP improves both
      sodium balance and cardiac remodeling and might be advantageous to ACE inhibitors
      for the treatment of decompensated CHF.

PMID- 15498827
TI  - Role of impaired myocardial relaxation in the production of elevated left
      ventricular filling pressure.
AB  - Although present in many patients with heart failure and a normal ejection
      fraction, the role of isolated impairments in active myocardial relaxation in the
      genesis of elevated filling pressures is not well characterized. Because of
      difficulties in determining the effect of prolonged myocardial relaxation in
      vivo, we used a cardiovascular simulated computer model. The effect of myocardial
      relaxation, as assessed by tau (exponential time constant of relaxation), on
      pulmonary vein pressure (PVP) and left ventricular end-diastolic pressure (LVEDP)
      was investigated over a wide range of tau values (20-100 ms) and heart rate (60
      140 beats/min) while keeping end-diastolic volume constant. Cardiac output was
      recorded over a wide range of tau and heart rate while keeping PVP constant. The
      effect of systolic intervals was investigated by changing time to end systole at
      the same heart rate. At a heart rate of 60 beats/min, increases in tau from a
      baseline to extreme value of 100 ms cause only a minor increase in PVP of 3 mmHg.
      In contrast, at 120 beats/min, the same increase in tau increases PVP by 23 mmHg.
      An increase in filling pressures at high heart rates was attributable to
      incomplete relaxation. The PVP-LVEDP gradient was not constant and increased with
      increasing tau and heart rate. Prolonged systolic intervals augmented the effects
      of tau on PVP. Impaired myocardial relaxation is an important determinant of PVP
      and cardiac output only during rapid heart rate and especially when combined with
      prolonged systolic intervals. These findings clarify the role of myocardial
      relaxation in the pathogenesis of elevated filling pressures characteristic of
      heart failure.

PMID- 15498828
TI  - Human neutrophils promote angiogenesis by a paracrine feedforward mechanism
      involving endothelial interleukin-8.
AB  - Neovascularization by sprouting angiogenesis is critical for inflammation
      mediated tissue remodeling and wound healing. We report here that human
      polymorphonuclear neutrophils (PMN) stimulated for 1 h with 100 nM N-formyl
      methionyl-leucyl-phenylalanine (fMLP) released a proangiogenic entity that
      induced sprouting of capillary-like structures in an in vitro angiogenesis assay.
      The effect was comparable to the response obtained on stimulation with 100 ng/ml
      basic FGF. The PMN-mediated response was inhibited by neutralizing antibodies
      against VEGF or IL-8. As measured by ELISA technique, we found that fMLP
      activated PMN (5 x 10(6)/ml) released 78 pg/ml IL-8 and 39 pg/ml VEGF within 1 h
      after stimulation. IL-8 release was blocked by actinomycin D or cycloheximide,
      but the inhibitors had no effect on VEGF release, suggesting that IL-8 secretion
      required de novo synthesis whereas VEGF was secreted from preformed stores.
      Accordingly, RT-PCR analysis revealed that IL-8 mRNA was upregulated on PMN
      stimulation, whereas the expression of VEGF mRNA was not affected. Moreover,
      supernatant derived from activated PMN induced upregulation of endothelial IL-8
      mRNA expression, suggesting that release of VEGF and IL-8 from activated PMN may
      activate a paracrine feedforward mechanism involving endothelial IL-8. Moreover,
      VEGF-induced upregulation of endothelial IL-8 expression as well as sprouting of
      capillary-like structures was inhibited by a neutralizing anti-IL-8 antibody.
      These findings suggest that bacteria-derived tripeptides stimulate human PMN to
      release VEGF and IL-8, which activate endothelial cells and induce angiogenesis
      by a paracrine feedforward mechanism involving endothelial IL-8 upregulation.

PMID- 15498829
TI  - Remote preconditioning reduces ischemic injury in the explanted heart by a KATP
      channel-dependent mechanism.
AB  - Local and remote ischemic preconditioning (IPC) reduce ischemia-reperfusion (I/R)
      injury and preserve cardiac function. In this study, we tested the hypothesis
      that remote preconditioning is memorized by the explanted heart and yields
      protection from subsequent I/R injury and that the underlying mechanism involves
      sarcolemmal and mitochondrial ATP-sensitive K(+) (K(ATP)) channels. Male Wistar
      rats (300-350 g) were randomized to a control (n = 10), a remote IPC (n = 10),
      and a local IPC group (n = 10). Remote IPC was induced by four cycles of 5 min of
      limb ischemia, followed by 5 min of reperfusion. Local IPC was induced by four
      cycles of 2 min of regional myocardial ischemia, followed by 3 min of
      reperfusion. The heart was excised within 5 min after the final cycle of
      preconditioning, mounted in a perfused Langendorff preparation for 40 min of
      stabilization, and subjected to 45 min of sustained ischemia by occluding the
      left coronary artery and 120 min of reperfusion. I/R injury was assessed as
      infarct size by triphenyltetrazolium staining. The influence of sarcolemmal and
      mitochondrial K(ATP) channels on remote preconditioning was assessed by the
      addition of glibenclamide (10 microM, a nonselective K(ATP) blocker), 5
      hydroxydecanoic acid (5-HD; 100 microM, a mitochondrial K(ATP) blocker), and HMR
      1098 (30 microM, a sarcolemmal K(ATP) blocker) to the Langendorff preparation
      before I/R. The role of mitochondrial K(ATP) channels as an effector mechanism
      for memorizing remote preconditioning was further studied by the effect of the
      specific mitochondrial K(ATP) activator diaxozide (10 mg/kg) on myocardial
      infarct size. Remote preconditioning reduced I/R injury in the explanted heart
      (0.17 +/- 0.03 vs. 0.39 +/- 0.05, P < 0.05) and improved left ventricular
      function during reperfusion compared with control (P < 0.05). Similar effects
      were obtained with diazoxide. Remote preconditioning was abolished by the
      addition of 5-HD and glibenclamide but not by HMR-1098. In conclusion, the
      protective effect of remote preconditioning is memorized in the explanted heart
      by a mechanism that involves mitochondrial K(ATP) channels.

PMID- 15498830
TI  - Pronounced HR variability after exercise in inferior ischemia: evidence that the
      cardioinhibitory vagal reflex is invoked by exercise-induced inferior ischemia.
AB  - Potent cardioinhibitory vagal reflex resulting in bradycardia and hypotension has
      been observed under particular conditions of transmural inferior ischemia and its
      reperfusion, such as those observed with acute infarction. However, whether
      exercise-induced ischemia with ST depressions that is subendocardial and that
      might be recurrently experienced in daily activities can evoke this reflex
      remains unknown. In patients with exercise-induced ST depressions due to either
      inferior [right coronary artery stenosis (RCA), n = 52] or anterior ischemia
      [left anterior descending artery stenosis (LAD), n = 51], we evaluated post
      exercise vagal activity (from 0 to 6 min) by the time constant of heart rate (HR)
      decay and HR variability by 30-s averages of the absolute values of successive RR
      interval differences (DeltaRR). Exercise parameters were similar between groups.
      The time constant was slightly but significantly shorter in RCA than LAD patients
      (79 +/- 24 vs. 93 +/- 29 s, P < 0.01). More significantly, DeltaRR early after
      exercise (0.5-2.5 min) was approximately twofold greater in RCA than LAD patients
      (from +76 to +118%, P < 0.001), indicating pronounced vagal activity stimulated
      by inferior ischemia. Revascularization prolonged the time constant (P < 0.05)
      and attenuated recovery DeltaRR in RCA patients (P < 0.05, n = 10) but did not
      change both parameters in LAD patients (n = 12). As well as acute inferior
      infarction, exercise-induced inferior subendocardial ischemia, which might
      recurrently occur in daily activities, activates the cardioinhibitory reflex.
      These new findings must be taken into account in interpreting vagal activity in
      patients with coronary artery disease.

PMID- 15498831
TI  - Peripheral-type benzodiazepine receptor-mediated action of steroidogenic acute
      regulatory protein on cholesterol entry into leydig cell mitochondria.
AB  - Hormone-induced steroid biosynthesis begins with the transfer of cholesterol from
      intracellular stores into mitochondria. Steroidogenic acute regulatory protein
      (StAR) and peripheral-type benzodiazepine receptor (PBR) have been implicated in
      this rate-determining step of steroidogenesis. MA-10 mouse Leydig tumor cells
      were treated with and without oligodeoxynucleotides (ODNs) antisense to PBR and
      StAR followed by treatment with saturating concentrations of human
      choriogonadotropin. Treatment with ODNs antisense but not missense for both
      proteins inhibited the respective protein expression and the ability of the cells
      to synthesize steroids in response to human choriogonadotropin. Treatment of the
      cells with either ODNs antisense to PBR or a transducible peptide antagonist to
      PBR resulted in inhibition of the accumulation of the mature mitochondrial 30-kDa
      StAR protein, suggesting that the presence of PBR is required for StAR import
      into mitochondria. Addition of in vitro transcribed/translated 37-kDa StAR or a
      fusion protein of Tom20 (translocase of outer membrane) and StAR (Tom/StAR) to
      mitochondria isolated from control cells increased pregnenolone formation.
      Mitochondria isolated from cells treated with ODNs antisense, but not missense,
      to PBR failed to form pregnenolone and respond to either StAR or Tom/StAR
      proteins. Reincorporation of in vitro transcribed/translated PBR, but not PBR
      missing the cholesterol-binding domain, into MA-10 mitochondria rescued the
      ability of the mitochondria to form steroids and the ability of the mitochondria
      to respond to StAR and Tom/StAR proteins. These data suggest that both StAR and
      PBR proteins are indispensable elements of the steroidogenic machinery and
      function in a coordinated manner to transfer cholesterol into mitochondria.

PMID- 15498832
TI  - Regulation of corticotropin-releasing hormone receptor type 1alpha signaling:
      structural determinants for G protein-coupled receptor kinase-mediated
      phosphorylation and agonist-mediated desensitization.
AB  - Attenuation of CRH receptor type 1 (CRH-R1) signaling activity might involve
      desensitization and uncoupling of CRH-R1 from intracellular effectors. We
      investigated the desensitization of native CRH-R in human myometrial cells from
      pregnant women and recombinant CRH-R1alpha stably overexpressed in human
      embryonic kidney (HEK) 293 cells. In both cell types, CRH-R1-mediated adenylyl
      cyclase activation was susceptible to homologous desensitization induced by
      pretreatment with high concentrations of CRH. Time course studies showed half
      maximal desensitization occurring after approximately 40 min of pretreatment and
      full recovery of CRH-R1alpha functional response within 2 h of removal of CRH
      pretreatment. In HEK 293 cells, desensitization of CRH-R1alpha was associated
      with receptor phosphorylation and subsequent endocytosis. To analyze the
      mechanism leading to CRH-R1alpha desensitization, we overexpressed a truncated
      beta-arrestin (319-418) and performed coimmunoprecipitation and G protein-coupled
      receptor kinase (GRK) translocation studies. We found that GRK3 and GRK6 are the
      main isoforms that interact with CRH-R1alpha, and that recruitment of GRK3
      requires Gbetagamma-subunits as well as beta-arrestin. Site-directed mutagenesis
      of Ser and Thr residues in the CRH-R1alpha C terminus, identified Thr399 as
      important for GRK-induced receptor phosphorylation and desensitization.We
      conclude that homologous desensitization of CRH-R1alpha involves the coordinated
      action of multiple GRK isoforms, Gbeta gamma dimers and beta-arrestin. Based on
      our identification of key amino acid(s) for GRK-dependent phosphorylation, we
      demonstrate the importance of the CRH-R1alpha carboxyl tail for regulation of
      receptor activity.

PMID- 15498833
TI  - c-Src regulates clathrin adapter protein 2 interaction with beta-arrestin and the
      angiotensin II type 1 receptor during clathrin- mediated internalization.
AB  - Beta-arrestins are multifunctional adapters involved in the internalization and
      signaling of G protein-coupled receptors (GPCRs). They target receptors to
      clathrin-coated pits (CCPs) through binding with clathrin and clathrin adapter 2
      (AP-2) complex. They also act as transducers of signaling by recruiting c-Src
      kinase to certain GPCRs. Here we sought to determine whether c-Src regulates the
      recruitment of AP-2 to beta-arrestin and the angiotensin II (Ang II) type 1
      receptor (AT1R) during internalization. We show that the agonist stimulation of
      native AT1R in vascular smooth muscle cells (VSMCs) induces the formation of an
      endogenous complex containing c-Src, beta-arrestins and AP-2. In vitro studies
      using coimmunoprecipitation experiments and a yeast three-hybrid assay reveal
      that c-Src stabilizes the agonist-independent association between beta-arrestin2
      and the beta-subunit of AP-2 independently of the kinase activity of c-Src.
      However, although c-Src expression promoted the rapid dissociation of AP-2 from
      both beta-arrestin and AT1R after receptor stimulation, a kinase-inactive mutant
      of c-Src failed to induce the dissociation of AP-2 from the agonist-occupied
      receptor. Thus, the consequence of c-Src in regulating the dissociation of AP-2
      from the receptor was also examined on the internalization of AT1R by depleting c
      Src in human embryonic kidney (HEK) 293 cells using a small interfering RNA
      strategy. Experiments in c-Src depleted cells reveal that AT1R remained mostly
      colocalized with AP-2 at the plasma membrane after Ang II stimulation, consistent
      with the observed delay in receptor internalization. Moreover,
      coimmunoprecipitation experiments in c-Src depleted HEK 293 cells and VSMCs
      showed an increased association of AP-2 to the agonist-occupied AT1R and beta
      arrestin, respectively. Together, our results support a role for c-Src in
      regulating the dissociation of AP-2 from agonist-occupied AT1R and beta-arrestin
      during the clathrin-mediated internalization of receptors and suggest a novel
      function for c-Src kinase in the internalization of AT1R.

PMID- 15498834
TI  - Nursing home litigation and tort reform: a case for exceptionalism.
AB  - The medical malpractice crisis that is currently spreading across the United
      States bears many similarities to earlier crises. One novel aspect of the current
      crisis is the explicit inclusion of litigation against nursing homes as a target
      of reform. Encouraged by the nursing home industry, policymakers are considering
      the extension of conventional medical malpractice tort reforms to the nursing
      home sector. In this article, we caution against such an approach. Nursing home
      litigation has a number of distinctive features that raise serious questions
      about the wisdom of implementing reforms generically across the care continuum.
      Drawing on findings from our previous study of nursing home litigation, we
      outline these features and argue for careful attention to them as policymakers
      evaluate options for reform.

PMID- 15498835
TI  - Measuring psychological well-being: insights from Thai elders.
AB  - PURPOSE: Psychological well-being, an important indicator of successful aging,
      may be conceptualized quite differently across cultures. Using a mixed-methods
      approach, we developed a measure of psychological well-being based on the
      indigenous expertise of Thai elders. DESIGN AND METHODS: Data were collected from
      older people in Thailand in four stages with staggered qualitative and
      quantitative methods: individual and focus group interviews (n = 67); a
      preliminary survey (n = 477); cognitive interviews (n = 30); and a second survey
      (n = 460). We analyzed the resulting psychological well-being items to identify
      their underlying factor structure and psychometric properties. RESULTS:
      Confirmatory factor analysis suggested that psychological well-being has two
      components: intrapersonal and interpersonal. The subscales for this measure have
      adequate reliability and validity. IMPLICATIONS: This research provides evidence
      for cultural variability in the nature of psychological well-being and highlights
      the importance of developing measures that are culturally relevant.

PMID- 15498836
TI  - Resources predicting positive and negative affect during the experience of
      stress: a study of older Asian Indian immigrants in the United States.
AB  - PURPOSE: Using the life stress model of psychological well-being, in this study
      we examined risks and resources predicting the occurrence of both positive and
      negative affect among older Asian Indian immigrants who experienced stressful
      life events. DESIGN AND METHODS: We collected data through a telephone survey of
      226 respondents (aged 50 years and older) in the Southeastern United States. We
      used hierarchical, negative binomial regression analyses to examine correlates of
      positive and negative affect. RESULTS: Different coping resources influenced
      positive and negative affect when stressful life events were controlled for.
      Being female was a common risk factor for poorer positive and increased negative
      affect. Satisfaction with friendships and a cultural or ethnic identity that is
      either bicultural or more American were predictive of greater positive affect.
      Greater religiosity and increased mastery were resources predicting less negative
      affect. IMPLICATIONS: Cognitive and structural interventions that increase
      opportunities for social integration, increasing mastery, and addressing
      spiritual concerns are discussed as ways of coping with stress to improve the
      well-being of individuals in this immigrant community.

PMID- 15498837
TI  - Lifetime trauma, emotional support, and life satisfaction among older adults.
AB  - PURPOSE: The purpose of this study is to examine the relationships among lifetime
      exposure to traumatic events, emotional support, and life satisfaction in three
      cohorts of older adults. DESIGN AND METHODS: Face-to-face interviews were
      conducted with a nationwide sample of 1,518 older people in 2003. Approximately
      500 elders were interviewed in each of the following age cohorts: Young-old (age
      65-74), old-old (75-84), and oldest-old (85 and older). RESULTS: The findings
      suggest that exposure to lifetime trauma is associated with less life
      satisfaction in all three age cohorts. The data further reveal that emotional
      support offsets the effects of trauma on feelings of life satisfaction in the old
      old and the oldest-old. The stress buffering properties of emotional support were
      especially evident in the oldest-old cohort. IMPLICATIONS: The findings
      underscore the need to develop interventions that help older people deal more
      effectively with lifetime trauma. Moreover, the results suggest that
      interventions providing emotional support may be especially helpful for the
      oldest-old.

PMID- 15498838
TI  - Using resident reports of quality of life to distinguish among nursing homes.
AB  - PURPOSE: We used measures created to assess the quality of life (QOL) of nursing
      home residents to distinguish among nursing facilities. DESIGN AND METHODS: We
      statistically adjusted scores for 10 QOL domains derived from standardized
      interviews with nursing home residents for age, gender, activities of daily
      living functioning, cognitive functioning, and length of stay, and then we
      aggregated them to the facility level. We compared the patterns across a sample
      of 40 facilities. We correlated facility characteristics with QOL scores.
      RESULTS: The pattern of QOL scores for each of the 10 domains was generally
      consistent within a given facility. Although resident characteristics played a
      major role in explaining variance, there were significant effects of facilities
      as well. Some modest relationships were found between facility characteristics
      such as ownership, percentage of private rooms, and rural-urban location and
      facility QOL scores. No effect of facility size was detected. IMPLICATIONS: This
      article shows that it is possible to differentiate among facilities on the basis
      of resident self-reported QOL. On the basis of our analysis, we find that a
      sample of 28 residents per facility is sufficient to generate a reliable QOL
      score for each of the domains studied.

PMID- 15498839
TI  - Work stressors and the quality of life in long-term care units.
AB  - PURPOSE: The purpose of this work was to examine how structural factors,
      residents' needs for physical and psychosocial assistance, and the work stressors
      experienced by employees are related to the quality of life of elderly residents
      in long-term care. DESIGN AND METHODS: Cross-sectional survey data were collected
      from 1,194 employees and 1,079 relatives of residents in 107 residential-home
      units and health-center bed wards. Data were analyzed using multilevel modeling.
      RESULTS: The majority of differences in both employees' and relatives'
      perceptions of residents' quality of life across units could be explained by work
      stressors such as time pressure. Large unit size was related to both increased
      time pressure among employees and reduced quality of life of residents.
      IMPLICATIONS: Long-term care units are encouraged to review their practices so
      that employee well-being is supported. Attention also should be focused on unit
      size, as small units appear better able to help employees cope with work stress,
      resulting in better quality of life for residents.

PMID- 15498840
TI  - Two models of managed long-term care: comparing PACE with a Medicaid-only plan.
AB  - PURPOSE: In this study an attempt is made to understand how a Medicaid-only
      managed long-term-care (MMLTC) plan for elders differs from the Program of All
      Inclusive Care for the Elderly (PACE), a fully integrated model, in terms of
      structure, operations, patient population, and service utilization. DESIGN AND
      METHODS: With the use of information from the Outcome and Assessment Information
      Set and administrative data from a MMLTC plan in New York City, enrollees were
      compared at the start of care and their first-year service utilization with PACE,
      using the PACE national data set. RESULTS: The plans differ in the range of
      services covered and in the larger number of members served by the MMLTC plan.
      The served populations differ in their sociodemographic profiles and have levels
      of functional need that are high, but they also differ in their relative severity
      of dependency in activities of daily living and instrumental activities of daily
      living. During the first year of enrollment, the utilization of traditional home-
      and community-based services was higher in PACE than in the MMLTC plan, although
      MMLTC plan members received much more care in the home. Total hospital
      utilization was lower in PACE, but nursing home utilization was higher.
      IMPLICATIONS: MMLTC is a feasible option for serving a population whose level of
      impairment is similar to that of PACE. Whereas PACE's reliance on adult day
      centers is seemingly associated with a stronger medical focus and lower hospital
      use, the MMLTC plan's emphasis on home-based personal care seems to be linked
      with lower nursing home use.

PMID- 15498841
TI  - The influence of rural location on utilization of formal home care: the role of
      Medicaid.
AB  - PURPOSE: This research examines the impact of rural-urban residence on formal
      home-care utilization among older people and determines whether and how Medicaid
      coverage influences the association between rural-urban location and risk of
      formal home-care use. DESIGN AND METHODS: We combined data from the 1998
      consolidated file of the Medical Expenditure Panel Survey Household Component
      with data from the Area Resource File to generate the analytical data set. We
      established two measures of formal home-care utilization: home care reimbursed
      through any source, and Medicare-reimbursed home health care. Our measures of
      rural-urban residence included metropolitan counties, nonmetropolitan counties
      having towns of at least 10,000 people, and nonmetropolitan counties with no
      towns of 10,000 people. We used logistic regression analyses to examine main
      effects and interaction effects of Medicaid coverage and residence on the two
      types of formal home care under controls for person-level characteristics and
      state fixed effects. RESULTS: The unadjusted logistic analyses demonstrate that
      older people who reside in the most rural counties (nonmetropolitan counties
      having no town of 10,000) are significantly more likely than metropolitan
      residents to use any formal home care and Medicare home health care. The fully
      adjusted logistic analysis results point to an interplay between residential
      status and Medicaid coverage with regard to formal home-care use. In comparison
      with metropolitan residents covered by Medicaid, the adjusted relative risk of
      any formal home-care use is significantly higher for Medicaid enrollees residing
      in nonmetropolitan counties having no town of 10,000 people. Use of Medicare home
      health care is significantly greater for residents of the most rural counties,
      irrespective of their Medicaid coverage, as well as Medicaid-covered residents of
      nonmetropolitan counties having a town of at least 10,000 people. IMPLICATIONS:
      In nonmetropolitan areas, Medicaid may be an important mechanism for linking
      older individuals with formal home care, especially Medicare home health care,
      and with the services that generate formal home care. Formal home care, including
      Medicare home health care, may substitute for less available forms of care in the
      most rural of nonmetropolitan areas. Therefore, policies that limit access to
      formal home care could lead to increased service-related vulnerabilities among
      older rural residents.

PMID- 15498842
TI  - Home care quality indicators (HCQIs) based on the MDS-HC.
AB  - PURPOSE: This study aimed to develop home care quality indicators (HCQIs) to be
      used by a variety of audiences including consumers, agencies, regulators, and
      policy makers to support evidence-based decision making related to the quality of
      home care services. DESIGN AND METHODS: Data from 3,041 Canadian and 11,252 U.S.
      home care clients assessed with the Minimum Data Set-Home Care (MDS-HC) were used
      to evaluate a series of indicators suggested by international experts and by
      focus groups conducted in Canada and the United States. Risk adjustment methods
      were derived and validated using data from Ontario and Michigan. RESULTS: Of the
      73 original candidate HCQIs, 22 were retained for the final list of recommended
      indicators. All but three indicators include risk adjusters based on individual
      level covariates. An agency-level risk adjustment was developed to correct for
      selection and ascertainment bias. IMPLICATIONS: The HCQIs are new tools providing
      a first step along the path of quality improvement for home care. These
      indicators can provide high-quality evidence on performance at the agency level
      and on a regional basis.

PMID- 15498843
TI  - Is telephone screening feasible? Accuracy and cost-effectiveness of identifying
      people medically eligible for home- and community-based services.
AB  - PURPOSE: To determine the accuracy of a telephone-screening system to identify
      persons eligible for home- and community-based long-term care. DESIGN AND
      METHODS: Data from Michigan telephone screens were compared to data from in
      person assessments using the Minimum Data Set for Home Care (MDS-HC). Weighted
      kappa statistics measured the level of agreement between the two assessments.
      RESULTS: Overall, recommendations based on the telephone screen produced a
      marginal match compared to recommendations based on in-person assessment. "False
      positives" (individuals scoring as more impaired on the telephone screen than in
      person) occurred in 27% of all cases, while "false negatives" (individuals
      scoring as less impaired on the telephone screen) only occurred among 6% of the
      callers. Neither individual screen questions, source of information, location of
      the individual, timing between screen and assessment, nor temporal changes
      accounted for mismatches. Telephone screens resulted in an 11% savings over the
      cost of providing in-person assessments to all program seekers. IMPLICATIONS: The
      telephone screen has utility as a broad targeting mechanism that allows agencies
      to avoid costly in-person assessments for all program seekers. Evidence does not
      support use of the telephone screen alone to determine either medical eligibility
      or a specific level of care.

PMID- 15498844
TI  - Interrater reliability of the outcomes and assessment information set: results
      from the field.
AB  - The Outcomes and Assessment Information Set (OASIS) is now used extensively for
      regulatory, reimbursement, research, and clinical purposes in home health care.
      However, little is known about the interrater reliability of OASIS items based on
      assessments from home-health-agency clinicians. Therefore, we evaluated OASIS
      item interrater reliability among 88 patients from 21 agencies. Of 25 items
      studied, all except 2 had weighted kappa values of kappa > or = 0.60. We conclude
      that OASIS item interrater reliability was highly adequate in this study, but we
      recommend routine interrater-reliability evaluation by agencies to maximize the
      quality of OASIS data nationally.

PMID- 15498845
TI  - Scarcity of HIV/AIDS risk-reduction materials targeting the needs of older adults
      among state departments of public health.
AB  - This study investigated the availability of printed human immunodeficiency
      virus/acquired immune deficiency syndrome (HIV/AIDS) education/prevention
      materials from state departments of public health within the United States, which
      specifically targeted the older adult population. Information on HIV/AIDS from
      public health departments in each of the 50 states was solicited, obtained, and
      analyzed for applicability to an older adult population. Although all 50 states
      responded to our request for publications, only 15 states (30%) provided
      publications that were specifically intended for an older adult audience. The
      title, date of publication, and publisher of publications that were considered
      "specific to older adults" are provided. These findings suggest that there is a
      general lack of HIV/AIDS prevention literature specifically tailored for older
      adults available through state departments of public health.

PMID- 15498846
TI  - Implementing a university-community-retail partnership model to facilitate
      community education on universal design.
AB  - PURPOSE: A collaborative partnership model was used to develop and implement a
      state-wide community education program on universal design. DESIGN AND METHODS:
      University faculty, extension professionals, older adult service agencies,
      service learning students, and a community retail chain made up the original
      partnership. RESULTS: This collaboration resulted in a five-stage partnership
      model. The model was used to develop and disseminate a consumer education program
      to promote aging in place. The five stages include (a) identifying partner
      strengths and shared learning, (b) program development, (c) implementing the
      universal design program, (d) facilitating collaborative outreach, and (e)
      shifting toward sustainable outreach. IMPLICATIONS: A lack of knowledge exists
      among consumers, builders, and health care professionals regarding strategies for
      aging in place. Collaborations between educators, outreach professionals,
      students, and a retail partner resulted in increased interest and awareness about
      universal design changes that enable seniors to age in place.

PMID- 15498847
TI  - Advancing the field of elder mistreatment: a new model for integration of social
      and medical services.
AB  - PURPOSE: The purpose of this work is to describe the development and operation of
      a new model for integration of medical and social services. The Vulnerable Adult
      Specialist Team (VAST) provides Adult Protective Services (APS) and criminal
      justice agencies with access to medical experts who examine medical and
      psychological injuries of victims of elder abuse. DESIGN AND METHODS: This
      retrospective, descriptive analysis included community-dwelling elders and adults
      with disabilities who were reported for mistreatment and referred to VAST (n =
      269). RESULTS: Most cases came from APS for mental status and physical
      examination for evidence of abuse. Cases referred to a medical response team (n =
      269) were significantly different from cases that were not referred (n = 9,505).
      IMPLICATIONS: Ninety-seven percent of those who referred cases to VAST indicated
      that the team was helpful in confirming abuse, documenting impaired capacity,
      reviewing medications and medical conditions, facilitating the conservatorship
      process, persuading the client or family to take action, and supporting the need
      for law enforcement involvement. As a result, VAST has become institutionalized
      in our county. Amenable to replication, medical response teams for elder abuse
      may be useful in other counties across the nation.

PMID- 15498848
TI  - Monocyte chemoattractant protein-1-induced angiogenesis is mediated by vascular
      endothelial growth factor-A.
AB  - Monocyte chemoattractant protein-1 (MCP-1) has been recognized as an angiogenic
      chemokine. In the present study, we investigated the detailed mechanism by which
      MCP-1 induces angiogenesis. We found that MCP-1 up-regulated hypoxia-inducible
      factor 1 alpha (HIF-1 alpha) gene expression in human aortic endothelial cells
      (HAECs), which induced vascular endothelial growth factor-A(165) (VEGF-A(165))
      expression in the aortic wall and HAECs through activation of p42/44 mitogen
      activated protein kinase (MAPK). In vivo angiogenesis assay using chick
      chorioallantoic membrane (CAM) showed that MCP-1-induced angiogenesis was as
      potent as that induced by VEGF-A(165) and completely inhibited by a VEGF
      inhibitor, Flt(2-11). The inhibition of RhoA small G protein did not affect MCP-1
      induced VEGF-A(165) production and secretion but completely blocked both MCP-1-
      and VEGF-A-induced new vessel formation, as determined by CAM assay. These
      results suggest that MCP-1-induced angiogenesis is composed largely of 2
      sequential steps: the induction of VEGF-A gene expression by MCP-1 and the
      subsequent VEGF-A-induced angiogenesis.

PMID- 15498849
TI  - Mechanism by which H-2g, a glucose analog of blood group H antigen, mediates
      angiogenesis.
AB  - The 4A11 antigen is a unique cytokine-inducible antigen up-regulated on
      rheumatoid arthritis (RA) synovial endothelial cells (ECs) compared with normal
      ECs. Previously, we showed that in soluble form, this antigen, Lewis(y)-6/H-5-2
      (Le(y)/H) or its glucose analog, 2-fucosyl lactose (H-2g), induced the expression
      of EC intercellular adhesion molecule-1 (ICAM-1) and leukocyte-endothelial
      adhesion through the Janus kinase 2 (JAK2)-signal transducer and activator of
      transcription 3 (STAT3) pathway. Currently, we show that H-2g induces release of
      EC angiogenic basic fibroblast growth factor (bFGF) and vascular endothelial
      growth factor (VEGF), an effect inhibited by decoy nuclear factor kappaB
      (NFkappaB) oligodeoxynucleotide (ODN). JAK2 and phosphoinositide-3 kinase (PI3K)
      are 2 upstream kinases of NFkappaB activated by H-2g, as confirmed by an
      inhibitor of kappa B kinase (IKKbeta) assay. In vitro, H-2g induces vascular
      sprouting in the rat aortic ring model, whereas blockade of JAK2, PI3K, or
      NFkappaB inhibits sprouting. Likewise, in the in vivo mouse Matrigel plug
      angiogenesis assay, chemical inhibitors and antisense or decoy ODNs of JAK2,
      PI3K, or NFkappaB decrease angiogenesis, confirming the importance of these
      pathways in H-2g-induced EC signaling. The critical role of Le(y)/H involvement
      in angiogenesis and its signaling pathways may provide new targets for therapy of
      diseases characterized by pathologic neovascularization.

PMID- 15498850
TI  - 15-Deoxy-delta 12,14-prostaglandin J2 induces apoptosis in human malignant B
      cells: an effect associated with inhibition of NF-kappa B activity and down
      regulation of antiapoptotic proteins.
AB  - Cyclopentenone prostaglandins are potent inhibitors of nuclear factor-kappa B (NF
      kappa B), a transcription factor with a critical role in promoting inflammation
      and connected with multiple aspects of oncogenesis and cancer cell survival. In
      the present report, we investigated the role of NF-kappa B in the antineoplastic
      activity of the cyclopentenone prostaglandin 15-deoxy-Delta(12,14)-PGJ(2) (15d
      PGJ(2)) in multiple myeloma (MM) and Burkitt lymphoma (BL) cells expressing
      constitutively active NF-kappa B. 15d-PGJ(2) was found to suppress constitutive
      NF-kappa B activity and potently induce apoptosis in both types of B-cell
      malignancies. 15d-PGJ(2)-induced apoptosis occurs through multiple caspase
      activation pathways involving caspase-8 and caspase-9, and is prevented by
      pretreatment with the pan-caspase inhibitor ZVAD (z-Val-Ala-Asp). NF-kappa B
      inhibition is accompanied by rapid down-regulation of NF-kappa B-dependent
      antiapoptotic gene products, including cellular inhibitor-of-apoptosis protein 1
      (cIAP-1), cIAP-2, X-chromosome-linked inhibitor-of-apoptosis protein (XIAP), and
      FLICE-inhibitory protein (cFLIP). These effects were mimicked by the proteasome
      inhibitor MG-132, but not by the peroxisome proliferator-activated receptor-gamma
      (PPAR-gamma) agonist troglitazone, suggesting that 15d-PGJ(2)-induced apoptosis
      is independent of PPAR-gamma. Knockdown of the NF-kappa B p65-subunit by
      lentiviral-mediated shRNA interference also resulted in apoptosis induction in
      malignant B cells with constitutively active NF-kappa B. The results indicate
      that inhibition of NF-kappa B plays a major role in the proapoptotic activity of
      15d-PGJ(2) in aggressive B-cell malignancies characterized by aberrant regulation
      of NF-kappa B.

PMID- 15498851
TI  - Preconditioning of NOD mice with anti-CD8 mAb and costimulatory blockade enhances
      chimerism and tolerance and prevents diabetes, while depletion of alpha beta-TCR+
      and CD4+ cells negates the effect.
AB  - Bone marrow transplantation blocks diabetes pathogenesis and reverses
      autoimmunity in nonobese diabetic (NOD) mice. However, there is a greater barrier
      to engraftment in the context of autoimmunity. In the present study, we
      characterized which recipient cells influence engraftment in prediabetic NOD
      mice, with the goal to replace myelotoxic conditioning with antigen-specific
      deletion of reactive host cells. Preconditioning of NOD mice with anti-CD8 and
      anti-CD154 monoclonal antibodies (mAbs) synergistically enhanced engraftment and
      significantly reduced the minimum total body irradiation (TBI) dose for
      engraftment. Strikingly, preconditioning with anti-CD4 mAb significantly impaired
      engraftment, negating the beneficial effect of anti-CD8, and resulted in a
      requirement for more TBI-based conditioning compared with controls conditioned
      with TBI alone. Similarly, more TBI was required when anti-T-cell receptor beta
      (TCRbeta) mAb was administered as preconditioning. The addition of anti-CD152 to
      CD154 preconditioning abrogated the engraftment-enhancing effect of anti-CD154.
      Taken together, these data indicate a role for CD4+ regulatory T cells in vivo
      which require signaling via CD152 in the induction of chimerism and tolerance in
      NOD recipients. Notably, disease prevention and reversal of autoimmunity was
      absolutely correlated with the establishment of chimerism. These studies have
      important implications for the design of novel clinical approaches to treat type
      1 diabetes.

PMID- 15498852
TI  - Smad7 alters cell fate decisions of human hematopoietic repopulating cells.
AB  - Intracellular Smad proteins mediate signal transduction of the transforming
      growth factor-beta (TGF-beta) superfamily that play pleiotropic roles in
      hematopoietic development, suggesting that intracellular Smad proteins may play
      key roles in hematopoietic regulation. Although inhibitory Smad7, which
      negatively regulates TGF-beta signaling, has been implicated in the development
      of mature hematopoietic cells, a role for Smad7 in regulating more primitive
      hematopoietic cells has yet to be examined. Here, Smad7 was overexpressed in
      primary human severe combined immunodeficient (SCID) repopulating cells (SRCs),
      representing a common myeloid/lymphoid precursor cell with the functional
      capacity to repopulate the bone marrow of nonobese diabetic (NOD)/SCID recipient
      mice. Retroviral transduction of Smad7 into human umbilical cord blood (CB)-SRCs
      caused a shift from lymphoid dominant engraftment toward increased myeloid
      contribution, and increased the myeloid-committed clonogenic progenitor frequency
      in reconstituted mice. Neither myeloid nor B-lymphoid lineage developmental
      stages were compromised by Smad7 overexpression, suggesting Smad7 regulates cell
      fate commitment decisions of myeloid/lymphoid precursors by augmenting myeloid
      differentiation at the expense of lymphoid commitment. In addition, global gene
      expression analysis using microarray was used to identify potential target genes
      regulated by Smad7 in primitive hematopoietic cells that may control this
      process. Our study demonstrates a novel and unexpected role for Smad7 in
      modulating the cell fate decisions of primary multipotent human repopulating
      cells and establishes a role for Smad7 in the development of primitive human
      hematopoietic cells.

PMID- 15498853
TI  - Cell type-specific regulation of von Willebrand factor expression by the E4BP4
      transcriptional repressor.
AB  - Mechanisms of tissue-restricted patterns of von Willebrand factor (VWF)
      expression involve activators and repressors that limit expression to endothelial
      cells and megakaryocytes. The relative transcriptional activity of the proximal
      VWF promoter was assessed in VWF-producing and -nonproducing cells, and promoter
      activity was highest in endothelial cells followed by megakaryocytes. Only basal
      VWF promoter activity was seen in nonendothelial cells. Here we identify a
      negative response element located at nucleotides (nts) +96/+105 and demonstrate,
      using chromatin immunoprecipitation (ChIP) analysis, that in vivo this sequence
      interacts with the E4BP4 transcriptional repressor. Differences in size and
      relative abundance of nuclear E4BP4 were observed. In HepG2 cells, low levels of
      larger forms of E4BP4 are present that directly interact with the negative
      response element. In VWF-expressing cells, high levels of smaller forms
      predominate with no evidence of direct DNA binding. However, in endothelial
      cells, mutation of the VWF E4BP4 binding motif not only restores but also further
      elevates VWF promoter activity, suggesting that E4BP4 may be part of a
      coordinated binding complex. These observations implicate this binding motif in
      repressing both activated and basal levels of VWF transcription by different cell
      type-specific mechanisms, and support the hypothesis that E4BP4 sequesters
      negative regulators of transcription, thereby enhancing activated gene
      expression.

PMID- 15498854
TI  - Angiopoietins can directly activate endothelial cells and neutrophils to promote
      proinflammatory responses.
AB  - Angiopoietin-1 (Ang1) and -2 (Ang2) are endothelial growth factors that bind to
      the tyrosine kinase receptor Tie2 and contribute to orchestrate blood vessel
      formation during angiogenesis. Ang1 mediates vessel maturation and integrity by
      the recruitment of pericytes. In contrast, Ang2 is classically considered as a
      Tie2 antagonist, counteracting the stabilizing action of Ang1. Inflammation
      exists in a mutually dependent association with angiogenesis and we have
      therefore studied the capacity of angiopoietins to modulate proinflammatory
      activities, namely P-selectin translocation and neutrophil adhesion onto
      endothelial cells. We observed that both Ang1 and Ang2 increased these biologic
      activities. Furthermore, combination of Ang1/Ang2 induced an additive effect on
      neutrophil adhesion but not on P-selectin translocation. In an attempt to clarify
      this phenomenon, we found that angiopoietins can directly activate neutrophils
      through Tie2 signaling as well as modulate platelet-activating factor (PAF)
      synthesis and beta(2) integrin functional up-regulation. Together, our data
      demonstrate that angiopoietins could promote acute recruitment of leukocytes,
      which might contribute to facilitate vascular remodeling and angiogenesis.

PMID- 15498855
TI  - Epstein-Barr virus nuclear antigen 2 induces interleukin-18 receptor expression
      in B cells.
AB  - Epstein-Barr virus (EBV) latently infects and immortalizes B lymphocytes and
      causes lymphoproliferative malignancies. We show here that the EBV nuclear
      antigen EBNA2 induces expression of the 2 chains of the interleukin-18 receptor
      (IL-18R) in Burkitt lymphoma (BL) cell lines and in nontransformed B cells.
      Activation of IL-18R expression by EBNA2 is independent of its interaction with
      the transcriptional repressor RBPJ kappa. It occurs in the absence of any other
      viral protein but requires de novo synthesis of cellular proteins. IL-18R
      induction is a highly specific function of EBNA2, because neither other EBV
      latent proteins nor the cellular proteins c-myc or Notch can exert this effect.
      Using cDNA microarray expression profiling, we find that the IL-18 receptor
      expressed in EBV-infected BL cells has signaling capacity, because IL-18
      significantly modified gene expression. We report that EBNA2 expression is
      associated with IL-18R expression in vivo in EBV-positive B-lymphomas from AIDS
      patients.

PMID- 15498856
TI  - Cord blood comprises antigen-experienced T cells specific for maternal minor
      histocompatibility antigen HA-1.
AB  - Umbilical cord blood transplantation is applied as treatment for mainly pediatric
      patients with hematologic malignancies. The clinical results show a relatively
      low incidence of graft-versus-host disease and leukemia relapse. Since maternal
      cells traffic into the fetus during pregnancy, we questioned whether cord blood
      has the potential to generate cytotoxic T cells specific for the hematopoietic
      minor histocompatibility (H) antigen HA-1 that would support the graft-versus
      leukemia effect. Here, we demonstrate the feasibility of ex vivo generation of
      minor H antigen HA-1-specific T cells from cord blood cells. Moreover, we
      observed pre-existing HA-1-specific T cells in cord blood samples. Both the
      circulating and the ex vivo-generated HA-1-specific T cells show specific and
      hematopoietic restricted lysis of human leukocyte antigen-A2(pos)/HA-1(pos) (HLA
      A2(pos)/HA-1(pos)) target cells, including leukemic cells. The cord blood-derived
      HA-1-specific cytotoxic T cells are from child origin. Thus, the so-called naive
      cord blood can comprise cytotoxic T cells directed at the maternal minor H
      antigen HA-1. The apparent immunization status of cord blood may well contribute
      to the in vivo graft-versus-leukemia activity after transplantation. Moreover,
      since the fetus cannot be primed against Y chromosome-encoded minor H antigens,
      cord blood is an attractive stem cell source for male patients.

PMID- 15498857
TI  - Novel chromosomal imbalances in mantle cell lymphoma detected by genome-wide
      array-based comparative genomic hybridization.
AB  - Mantle cell lymphoma (MCL) is an aggressive, highly proliferative B-cell non
      Hodgkin lymphoma, characterized by the specific t(11;14)(q13;q32) translocation.
      It is well established that this translocation alone is not sufficient to promote
      MCL development, but that additional genetic changes are essential for malignant
      transformation. We have identified such additional tumorigenic triggers in MCL
      tumors, by applying genome-wide array-based comparative genomic hybridization
      with an 800-kilobase (kb) resolution. This strategy, combined with a newly
      developed statistical approach, enabled us to confirm previously reported genomic
      alterations such as loss of 1p, 6q, 11q, 13q and gain of 3q and 8q, but it also
      facilitated the detection of novel recurrent genomic imbalances, such as gain of
      4p12-13 and loss of 20p12.1-12.3, 20q12-13.2, 22q12.1-12.3, and 22q13.31-13.32.
      Genomic hotspot detection allowed for the identification of small genomic
      intervals that are frequently affected (57%-93%), resulting in interesting
      positional candidate genes such as KITLG, GPC5, and ING1. Finally, by assessing
      multiple biopsies from the same patient, we show that seemingly stable genomes do
      show subtle genomic changes over time. The follow-up of multiple biopsies of
      patients with MCL by high-resolution genomic profiling is expected to provide us
      with new clues regarding the relation between clinical outcome and in vivo
      cytogenetic evolution.

PMID- 15498858
TI  - A STAT5 modifier locus on murine chromosome 7 modulates engraftment of
      hematopoietic stem cells during steady-state hematopoiesis.
AB  - Homologous disruption of expression of signal transducer and activator of
      transcription 5a (STAT5a) and STAT5b (STAT5ab(-/-)) in mice results in
      hematopoietic stem cells (HSCs) that can engraft irradiated hosts alone but are
      noncompetitive against wild-type HSCs. To explore mechanisms for this phenotype,
      we crossed the STAT5 mutations onto an HW80 background congenic to the original
      C57BL/6 that differs in a small chromosome 7 genomic locus. We previously
      demonstrated that C57BL/6 or HW80 background STAT5ab(-/-) bone marrow (BM) cells
      showed equal repopulating function either competitively or noncompetitively in
      irradiated hosts. However, one intraperitoneal injection of wild-type green
      fluorescent protein (GFP) transgenic BM cells into unconditioned newborn STAT5ab(
      /-) recipients of either background was sufficient for high-level donor
      engraftment. Furthermore, haploinsufficiency of STAT5 (STAT5ab(+/-)) allowed
      improved engraftment over wild-type recipients, indicating a dose-dependent
      requirement for STAT5 activation. In reciprocal experiments, STAT5ab(-/-) BM was
      transplanted into nonirradiated W/W(v) hosts. In these mice, C57BL/6 STAT5ab(-/-)
      BM cells were 10-fold more defective in long-term engraftment than control wild
      type BM cells and HW80 STAT5ab(-/-) BM cells were 5- to 10-fold more defective
      than C57BL/6 STAT5ab(-/-) BM cells. Therefore, we conclude that STAT5 plays a
      critical role during steady-state HSC engraftment and a chromosome 7 modifier
      locus regulates this activity.

PMID- 15498859
TI  - Pim-1 is up-regulated by constitutively activated FLT3 and plays a role in FLT3
      mediated cell survival.
AB  - Constitutively activating internal tandem duplication (ITD) mutations of the
      receptor tyrosine kinase FLT3 (Fms-like tyrosine kinase 3) play an important role
      in leukemogenesis, and their presence is associated with poor prognosis in acute
      myeloid leukemia (AML). To better understand FLT3 signaling in leukemogenesis, we
      have examined the changes in gene expression induced by FLT3/ITD or
      constitutively activated wild-type FLT3 expression. Microarrays were used with
      RNA harvested before and after inhibition of FLT3 signaling. Pim-1 was found to
      be one of the most significantly down-regulated genes upon FLT3 inhibition. Pim-1
      is a proto-oncogene and is known to be up-regulated by signal transducer and
      activator of transcription 5 (STAT5), which itself is a downstream target of FLT3
      signaling. Quantitative polymerase chain reaction (QPCR) confirmed the microarray
      results and demonstrated approximately 10-fold decreases in Pim-1 expression in
      response to FLT3 inhibition. Pim-1 protein also decreased rapidly in parallel
      with decreasing autophosphorylation activity of FLT3. Enforced expression of
      either the 44-kDa or 33-kDa Pim-1 isotypes resulted in increased resistance to
      FLT3 inhibition-mediated cytotoxicity and apoptosis. In contrast, expression of a
      dominant-negative Pim-1 construct accelerated cytotoxicity in response to FLT3
      inhibition and inhibited colony growth of FLT3/ITD-transformed BaF3 cells. These
      findings demonstrate that constitutively activated FLT3 signaling up-regulates
      Pim-1 expression in leukemia cells. This up-regulation contributes to the
      proliferative and antiapoptotic pathways induced by FLT3 signaling.

PMID- 15498860
TI  - IFN-gamma gene polymorphisms associate with development of EBV+
      lymphoproliferative disease in hu PBL-SCID mice.
AB  - Posttransplantation lymphoproliferative disorder (PTLD) is a devastating post
      transplantation complication often associated with Epstein-Barr virus (EBV).
      Although the type and length of immunosuppression are risk factors, a patient's
      inherent immune capacity also likely contributes to this disorder. This report
      uses severe-combined immunodeficient mice given injections of human peripheral
      blood leukocytes (hu PBL-SCID [Severe Combined Immunodeficient] mice) to test the
      hypothesis that cytokine genotype associates with the development of EBV
      associated lymphoproliferative disease (LPD). We observed that the A/A
      (adenosine/adenosine) genotype for base + 874 of the interferon gamma (IFN-gamma)
      gene was significantly more prevalent in PBLs producing rapid, high-penetrance
      LPD in hu PBL-SCID mice, compared to PBLs producing late, low-penetrance LPD or
      no LPD. In examining the relationship between genotype and cytolytic T-lymphocyte
      (CTL) function, transforming growth factor beta (TGF-beta) inhibited
      restimulation of CTLs in PBLs with adenosine at IFNG base + 874, but not in PBLs
      homozygous for thymidine. Importantly, neutralization of TGF-beta in hu PBL-SCID
      mice injected with A/A genotype PBLs resulted in reduced LPD development and
      expanded human CD8(+) cells. Thus, our data show that TGF-beta may promote tumor
      development by inhibiting CTL restimulation and expansion. Further, our data
      indicate that IFNG genotype may provide valuable information for both identifying
      transplant recipients at greater risk for PTLD and developing preventive and
      curative strategies.

PMID- 15498861
TI  - Do beta-globin, GATA-1,or EpoR regulatory domains specifically mark erythroid
      progenitors in transgenic reporter mice?

PMID- 15498862
TI  - The WHO classification of mature T-cell leukemias.

PMID- 15498863
TI  - Best therapy for primary amyloidosis, a not-yet-solved question.

PMID- 15498864
TI  - The role of PBSCT in treatment of AL amyloidosis is far from settled.

PMID- 15498865
TI  - IL-1 gene cluster polymorphisms and development of primary gastric B-cell
      lymphoma in Helicobacter pylori infection.

PMID- 15498866
TI  - The PRV-1 gene expression in essential thrombocythemia.

PMID- 15498867
TI  - A systematic method for identifying small-molecule modulators of protein-protein
      interactions.
AB  - Discovering small-molecule modulators of protein-protein interactions is a
      challenging task because of both the generally noncontiguous, large protein
      surfaces that form these interfaces and the shortage of high-throughput
      approaches capable of identifying such rare inhibitors. We describe here a robust
      and flexible methodology that couples disruption of protein-protein complexes to
      host cell survival. The feasibility of this approach was demonstrated through
      monitoring a small-molecule-mediated protein-protein association (FKBP12
      rapamycin-FRAP) and two cases of dissociation (homodimeric HIV-1 protease and
      heterodimeric ribonucleotide reductase). For ribonucleotide reductase, we
      identified cyclic peptide inhibitors from genetically encoded libraries that
      dissociated the enzyme subunits. A solid-phase synthetic strategy and peptide
      ELISAs were developed to characterize these inhibitors, resulting in the
      discovery of cyclic peptides that operate in an unprecedented manner, thus
      highlighting the strengths of a functional approach. The ability of this method
      to process large libraries, coupled with the benefits of a genetic selection,
      allowed us to identify rare, uniquely active small-molecule modulators of protein
      protein interactions at a frequency of less than one in 10 million.

PMID- 15498868
TI  - Role of proneuregulin 1 cleavage and human epidermal growth factor receptor
      activation in hypertonic aquaporin induction.
AB  - Mammalian cells are confronted with changes in extracellular osmolality at
      various sites, including the aqueous layer above the lung epithelium. Hypertonic
      shock induces the activation of mitogen-activated protein kinases and the
      expression of a defined set of genes, including aquaporins. We investigated
      upstream components of the response to hypertonicity in lung epithelial cells and
      found that before extracellular signal-regulated kinase activation and aquaporin
      synthesis, the membrane-bound prohormone neuregulin 1-beta is cleaved and binds
      to human epidermal growth factor receptor 3 (HER3). The signaling is prevented by
      matrix metalloproteinase inhibition, inhibition of neuregulin 1-beta binding to
      HER3, and inhibition of HER tyrosine kinase activity. Inhibition of HER
      activation interferes with the hypertonic induction of two different aquaporins
      in three distinct cell lines of mouse and human origin. We propose that ligand
      dependent HER activation constitutes a generalized signaling principle in the
      mammalian hypertonic stress response relevant to aquaporin expression.

PMID- 15498869
TI  - 3-hydroxy-3-methylglutaryl-CoA synthase intermediate complex observed in "real
      time".
AB  - The formation of carbon-carbon bonds via an acyl-enzyme intermediate plays a
      central role in fatty acid, polyketide, and isoprenoid biosynthesis. Uniquely
      among condensing enzymes, 3-hydroxy-3-methylglutaryl (HMG)-CoA synthase (HMGS)
      catalyzes the formation of a carbon-carbon bond by activating the methyl group of
      an acetylated cysteine. This reaction is essential in Gram-positive bacteria, and
      represents the first committed step in human cholesterol biosynthesis. Reaction
      kinetics, isotope exchange, and mass spectroscopy suggest surprisingly that HMGS
      is able to catalyze the "backwards" reaction in solution, where HMG-CoA is
      cleaved to form acetoacetyl-CoA (AcAc-CoA) and acetate. Here, we trap a complex
      of acetylated HMGS from Staphylococcus aureus and bound acetoacetyl-CoA by cryo
      cooling enzyme crystals at three different times during the course of its back
      reaction with its physiological product (HMG-CoA). This nonphysiological
      "backwards" reaction is used to understand the details of the physiological
      reaction with regards to individual residues involved in catalysis and
      substrate/product binding. The structures suggest that an active-site glutamic
      acid (Glu-79) acts as a general base both in the condensation between acetoacetyl
      CoA and the acetylated enzyme, and the hydrolytic release of HMG-CoA from the
      enzyme. The ability to trap this enzyme-intermediate complex may suggest a role
      for protein dynamics and the interplay between protomers during the normal course
      of catalysis.

PMID- 15498870
TI  - Conserved residues in the Plasmodium vivax Duffy-binding protein ligand domain
      are critical for erythrocyte receptor recognition.
AB  - Malaria merozoite invasion of human erythrocytes depends on recognition of
      specific erythrocyte surface receptors by parasite ligands. Plasmodium vivax
      merozoite invasion is totally dependent on the recognition of the Duffy blood
      group antigen by the parasite ligand Duffy-binding protein (DBP). Receptor
      recognition by P. vivax relies on a cysteine-rich domain, the DBL domain or
      region II, at the N terminus of the extracellular portion of DBP. The minimal
      region of the DBP implicated for receptor recognition lies between cysteines 4
      and 8 of the DBL domain, which is a region that also has the highest rate of
      allelic polymorphisms among parasite isolates. We previously found that allelic
      polymorphisms in this region altered the P. vivax DBL domain antigenic character,
      which contrasts with changes in receptor specificity attributed to polymorphisms
      in some homologous ligands of Plasmodium falciparum. To further investigate the
      relative importance of conserved and polymorphic residues within this DBL central
      region, we identified residues critical for receptor recognition by site-directed
      mutagenesis. Seventy-seven surface-predicted residues of the Sal-1 DBL domain
      were substituted with alanine and assayed for erythrocyte binding activity by
      expression of the mutant proteins on the surface of transiently transfected COS
      cells. The functional effect of alanine substitution varied from nil to complete
      loss of DBL erythrocyte-binding activity. Mutations that caused loss of ligand
      function mostly occurred in discontinuous clusters of conserved residues, whereas
      nearly all mutations in polymorphic residues did not affect erythrocyte binding.
      These data delineate DBL domain residues essential for receptor recognition.

PMID- 15498871
TI  - Correction of ATM gene function by aminoglycoside-induced read-through of
      premature termination codons.
AB  - Approximately 14% of genetic mutations in patients with ataxia-telangiectsia (A
      T) are single-nucleotide changes that result in primary premature termination
      codons (PTCs), either UAA, UAG, or UGA. The purpose of this study was to explore
      a potential therapeutic approach for this subset of patients by using
      aminoglycosides to induce PTC read-through, thereby restoring levels of full
      length ATM (A-T mutated) protein. In experiments using a modified in vitro cDNA
      coupled transcription/translation protein truncation test, 13 A-T cell lines
      carrying PTC mutations in different contexts exhibited read-through expression of
      ATM fragments, with three of four aminoglycosides tested. In ex vivo experiments
      with lymphoblastoid cell lines, we used radiosensitivity, radioresistant DNA
      synthesis, and irradiation-induced autophosphorylation of ATM Ser-1981 to show
      that the aminoglycoside-induced full-length ATM protein was functional and
      corrected, to various extents, the phenotype of A-T cells. These results
      encourage further testing of other compounds in this class, as well as follow up
      animal studies. Because some A-T patients with 5-20% of normal levels of ATM
      protein show slower neurological progression, A-T may prove to be a good model
      for aminoglycoside-induced read-through therapy.

PMID- 15498872
TI  - Selective interaction between nonribosomal peptide synthetases is facilitated by
      short communication-mediating domains.
AB  - Nonribosomal peptide synthetases (NRPSs) catalyze the formation of structurally
      diverse and biologically important peptides. Given their modular organization,
      NRPSs provide an enormous potential for biocombinatorial approaches to generate
      novel bioactive compounds. Crucial for the exploitation of this potential is a
      profound knowledge of the intermolecular communication between partner NRPSs. The
      overall goal of this study was to understand the basis of protein-protein
      communication that facilitates the selective interaction in these multienzyme
      complexes. On this account, we studied the relevance of short regions at the
      termini of the NRPSs tyrocidine (Tyc) synthetases TycA, TycB, and TycC,
      constituting the Tyc biosynthetic template. In vitro and in vivo investigations
      of C-terminal deletion mutants of the initiation module TycA provided evidence
      for the existence and impact of short communication-mediating (COM) domains.
      Their decisive role in protein-protein recognition was subsequently proven by
      means of COM domain-swapping experiments. Substitution of the terminal COM
      domains between the donor modules TycA and TycB3, as well as between the acceptor
      modules TycB1 and TycC1, clearly demonstrated that matching pairs of COM domains
      are both necessary and sufficient for the establishment of communication between
      partner NRPSs in trans. These results corroborated the generality of COM domains,
      which were subsequently exploited to induce crosstalk, even between NRPSs derived
      from different biosynthetic systems. In conclusion, COM domains represent
      interesting tools for biocombinatorial approaches, which, for example, could be
      used for the generation of innovative natural product derivatives.

PMID- 15498873
TI  - Innate immunity in Arabidopsis thaliana: lipopolysaccharides activate nitric
      oxide synthase (NOS) and induce defense genes.
AB  - Lipopolysaccharides (LPS) are cell-surface components of Gram-negative bacteria
      and are microbe-/pathogen-associated molecular patterns in animal pathosystems.
      As for plants, the molecular mechanisms of signal transduction in response to LPS
      are not known. Here, we show that Arabidopsis thaliana reacts to LPS with a rapid
      burst of NO, a hallmark of innate immunity in animals. Fifteen LPS preparations
      (among them Burkholderia cepacia, Pseudomonas aeruginosa, and Erwinia carotovora)
      as well as lipoteichoic acid from Gram-positive Staphylococcus aureus were found
      to trigger NO production in suspension-cultured Arabidopsis cells as well as in
      leaves. NO was detected by confocal laser-scanning microscopy in conjunction with
      the fluorophore 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate, by
      electron paramagnetic resonance, and by a NO synthase (NOS) assay. The source of
      NO was addressed by using T-DNA insertion lines. Interestingly, LPS did not
      activate the pathogen-inducible varP NOS, but AtNOS1, a distinct NOS previously
      associated with hormonal signaling in plants. A prominent feature of LPS
      treatment was activation of defense genes, which proved to be mediated by NO.
      Northern analyses and transcription profiling by using DNA microarrays revealed
      induction of defense-associated genes both locally and systemically. Finally,
      AtNOS1 mutants showed dramatic susceptibility to the pathogen Pseudomonas
      syringae pv. tomato DC3000. In sum, perception of LPS and induction of NOS
      contribute toward the activation of plant defense responses.

PMID- 15498874
TI  - Large-scale cDNA transfection screening for genes related to cancer development
      and progression.
AB  - A large-scale assay was performed by transfecting 29,910 individual cDNA clones
      derived from human placenta, fetus, and normal liver tissues into human hepatoma
      cells and 22,926 cDNA clones into mouse NIH 3T3 cells. Based on the results of
      colony formation in hepatoma cells and foci formation in NIH 3T3 cells, 3,806
      cDNA species (8,237 clones) were found to possess the ability of either
      stimulating or inhibiting cell growth. Among them, 2,836 (6,958 clones) were
      known genes, 372 (384 clones) were previously unrecognized genes, and 598 (895
      clones) were unigenes of uncharacterized structure and function. A comprehensive
      analysis of the genes and the potential mechanisms for their involvement in the
      regulation of cell growth is provided. The genes were classified into four
      categories: I, genes related to the basic cellular mechanism for growth and
      survival; II, genes related to the cellular microenvironment; III, genes related
      to host-cell systemic regulation; and IV, genes of miscellaneous function. The
      extensive growth-regulatory activity of genes with such highly diversified
      functions suggests that cancer may be related to multiple levels of cellular and
      systemic controls. The present assay provides a direct genomewide functional
      screening method. It offers a better understanding of the basic machinery of
      oncogenesis, including previously undescribed systemic regulatory mechanisms, and
      also provides a tool for gene discovery with potential clinical applications.

PMID- 15498877
TI  - Place of newer quinolones and rifampicin in the treatment of Gram-positive bone
      and joint infections.

PMID- 15498875
TI  - Epstein-Barr virus-encoded LMP2A regulates viral and cellular gene expression by
      modulation of the NF-kappaB transcription factor pathway.
AB  - Epstein-Barr virus (EBV)-associated malignancies display distinct patterns of
      virus latent gene expression that reflect the complex interplay between the virus
      and its host cell. In the EBV-associated epithelial tumor nasopharyngeal
      carcinoma (NPC), the virus-encoded latent membrane protein LMP2A is consistently
      expressed whereas the oncogenic LMP1 protein appears to be restricted to only a
      proportion of tumors. In an attempt to understand the contribution of LMP2A to
      the pathogenesis of NPC, we established carcinoma cell lines stably infected in
      vitro with either a wild-type recombinant EBV (rEBV) or a mutant rEBV in which
      LMP2A is deleted (rEBV-2A). An NPC-like pattern of EBV gene expression including
      LMP2A but not LMP1 was consistently observed in carcinoma cells infected with
      rEBV. However, carcinoma cells infected with rEBV-2A expressed high levels of
      LMP1 from the signal transducer and activator of transcription (STAT)-regulated
      L1-TR promoter. Consistent with this effect, basal STAT activity was reduced in
      rEBV-infected carcinoma cells, and this repression was relieved in the absence of
      LMP2A. This modulation of STAT activity correlated with the ability of LMP2A to
      inhibit the autocrine secretion of IL-6 from carcinoma cell lines. Exogenous IL-6
      was able to induce expression of LMP1 by means of STAT3 activation both in rEBV
      infected carcinoma cell lines and in the EBV-positive C666-1 NPC cell line. The
      LMP2A-mediated suppression of IL-6 was a consequence of NF-kappaB inhibition.
      These data reveal that LMP2A modulates two key transcription factor pathways in
      carcinoma cells and suggest that this finding may be important in the
      pathogenesis of EBV-associated tumors.

PMID- 15498878
TI  - Dissemination of vancomycin-resistant enterococci among haemodialysis patients in
      Athens, Greece.
AB  - OBJECTIVES: Vancomycin-resistant enterococci (VRE) may colonize haemodialysis
      patients, but their epidemiology in this population is not well defined. Within
      the few last years, VRE strains have emerged and are increasingly isolated in the
      nosocomial environment in Greece, but colonization of dialysis patients has never
      been evaluated before. This study sought to determine the epidemiology of VRE
      colonization within this high-risk population and define the risk factors.
      MATERIALS AND METHODS: During a 4 month period, rectal swabs or faecal specimens
      were collected from 334 consecutive outpatients, who were treated at four
      independent dialysis units located in the same area of Athens and referring
      patients to the same local hospital. The relatedness of isolates was defined by
      molecular typing, and demographic and clinical patient data were recorded.
      RESULTS: Thirteen multiresistant Enterococcus faecium vanA strains were isolated
      corresponding to a colonization frequency of 3.9%. They were separated into seven
      clusters: type A (two strains), type B (six strains) and types C to G (one strain
      each). Type B strains originated from three units, while a single unit
      demonstrated four type B and two type A strains. Univariate statistical analysis
      revealed that prior hospitalization (P=0.001), prior administration of
      antimicrobials (P=0.026) and male gender (P=0.019) were associated with VRE
      colonization. CONCLUSIONS: In Greece, haemodialysis patients are colonized with
      VRE at a low frequency. The predominance of one clone and its isolation from
      several units strongly indicate interfacility transmission of strains, most
      probably within a health care environment shared by all patients.

PMID- 15498879
TI  - Androgenic induction of growth and differentiation in the rodent uterus involves
      the modulation of estrogen-regulated genetic pathways.
AB  - The androgen receptor (AR) is expressed in the uterus; however, the role of AR in
      female reproductive physiology is poorly understood. Here we examined the effects
      of androgens on uterine growth and gene expression in adult ovariectomized rats.
      Nonaromatizable AR-selective agonists potently stimulate hypertrophy and induce
      significant myometrial expansion distinct from that induced by 17beta-estradiol
      (E2). In the endometrium, androgens only modestly increase epithelial cell height
      and antagonize the trophic effects of E2. To identify underlying mechanisms,
      global changes in RNA levels 24 h after stimulation with E2 and 5alpha
      dihydrotestosterone (DHT) were compared. A total of 491 genes were differentially
      expressed after E2 treatment, including key regulators of tissue remodeling, cell
      signaling, metabolism, and gene expression. Of the 164 transcripts regulated by
      DHT, 86% were also affected by E2, including trophic genes like IGF-I and
      epithelial secretory genes such as uterocalin. In estrogen receptor (ER)alpha
      knockout mice, DHT cannot induce uterine growth, suggesting a key role for
      ERalpha. However, DHT appears not to activate ERalpha directly because DHT
      induction of IGF-I is blocked by the AR antagonist bicalutamide, and multiple
      genes regulated directly by ERalpha were not induced by DHT. The similarity
      between estrogens and androgens instead could reflect general trophic signaling
      in reproductive tissues because 93 of the 503 genes regulated in the uterus are
      similarly affected during prostate growth. Thus androgens regulate the trophic
      environment and architecture of the rodent uterus via a gene expression program
      that is overlapping but distinct from the estrogen response.

PMID- 15498880
TI  - Estrogen acidifies vaginal pH by up-regulation of proton secretion via the apical
      membrane of vaginal-ectocervical epithelial cells.
AB  - The objective of this study was to assess estrogen-dependent cellular mechanisms
      that could contribute to the acid pH of the vaginal lumen. Cultures of normal
      human cervical-vaginal epithelial (hECE) cells and endocervical cells were grown
      on filters, and acidification of the extracellular solutions on the luminal (L
      pHo) and contraluminal (CL-pHo) sides was measured. The hECE cells and
      endocervical cells decreased CL-pHo from 7.40 to 7.25 within 20-30 min of
      incubation in basic salt solution. Endocervical cells also produced a similar
      decrease in L-pHo. In contrast, hECE cells acidified L-pHo down to pH 7.05 when
      grown as monoculture and down to pH 6.05 when grown in coculture with human
      cervical fibroblasts. This enhanced acid secretion into the luminal compartment
      was estrogen dependent because removal of endogenous steroid hormones attenuated
      the effect, whereas treatment with 17beta-estradiol restored it. The 17beta
      estradiol effect was dose dependent (EC50 0.5 nm) and could be mimicked by
      diethylstilbestrol and in part by estrone and tamoxifen. Preincubation with ICI
      182780, but not with progesterone, blocked the estrogen effect. Preincubation of
      cells with the V-ATPase blocker bafilomycin A1, when administered to the luminal
      solution, attenuated the baseline and estrogen-dependent acid secretion into the
      luminal solution. Treatment with EGTA, to abrogate the tight junctional
      resistance, blocked the decrease in L-pHo and stimulated a decrease in CL-pHo,
      indicating that the tight junctions are necessary for maintaining luminal
      acidification. We conclude that vaginal-ectocervical cells acidify the luminal
      canal by a mechanism of active proton secretion, driven in part by V-H+-ATPase
      located in the apical plasma membrane and that the baseline active net proton
      secretion occurs constitutively throughout life and that this acidification is up
      regulated by estrogen.

PMID- 15498881
TI  - A fully functional proopiomelanocortin/melanocortin-1 receptor system regulates
      the differentiation of human scalp hair follicle melanocytes.
AB  - The proopiomelanocortin (POMC)-derived peptides, ACTH and alpha-MSH, are the
      principal mediators of human skin pigmentation via their action at the
      melanocortin-1 receptor (MC-1R). Recent data have demonstrated the existence of a
      functionally active beta-endorphin/mu-opiate receptor system in both epidermal
      and hair follicle melanocytes, whereby beta-endorphin can regulate melanogenesis,
      dendricity, and proliferation in these cells. However, a role for ACTH and alpha
      MSH in the regulation of the human follicular pigmentary unit has not been
      determined. This study was designed to examine the involvement of ACTH and the
      alpha-MSH/MC-1R system in human follicular melanocyte biology. To address this
      question we employed RT-PCR and immunohisto/cytochemistry, and a functional role
      for these POMC peptides was assessed in follicular melanocyte cultures. Human
      scalp hair follicle melanocytes synthesized and processed POMC. ACTH and alpha
      MSH in association with their processing enzymes and MC-1R are expressed in human
      follicular melanocytes at the message level in vitro and at the protein level
      both in situ and in vitro. The expression of the POMC/MC-1R receptor system was
      confined only to subpopulations of poorly and moderately differentiated
      melanocytes. In addition, functional studies revealed that ACTH and alpha-MSH are
      able to promote follicular melanocyte differentiation by up-regulating
      melanogenesis, dendricity, and proliferation in less differentiated melanocyte
      subpopulations. Thus, these findings suggest a role for these POMC peptides in
      regulating human hair follicle melanocyte differentiation.

PMID- 15498882
TI  - Long-lived growth hormone receptor knockout mice: interaction of reduced insulin
      like growth factor i/insulin signaling and caloric restriction.
AB  - Reduced IGF-I/insulin signaling and caloric restriction (CR) are known to extend
      the life span and delay age-related diseases. To address the interaction of these
      two interventions, we subjected normal (N) and long-lived GH receptor knockout
      (GHRKO) mice to CR for 20 months starting at weaning. We also used bovine GH
      transgenic (bGH Tg) mice, which overexpress GH and are short-lived and insulin
      resistant, for comparison. Circulating insulin and IGF-I levels were reduced by
      CR in N animals, whereas GHRKO animals exhibited very low insulin and
      undetectable IGF-I. Consistently, hepatic Akt phosphorylation was reduced by CR
      and was very low in GHRKO mice. bGH Tg mice exhibited increased active Akt. The
      forkhead box O1 (Foxo1) transcription factor was additively increased by CR and
      GHRKO at the mRNA level. However, Foxo1 protein levels were only elevated in
      GHRKO mice. The coactivator peroxisome proliferator-activated receptor-gamma
      coactivator 1alpha was increased at both gene and protein levels in GHRKO mice. N
      CR and GHRKO mice also exhibited increased phosphorylated cAMP response element
      binding protein and active p38 compared with the N ad libitum-fed mice, and the
      levels of these proteins were greatly diminished in bGH Tg mice. The protein
      levels of the deacetylase sirtuin 1 (SIRT1) were elevated in the two CR groups
      and, unexpectedly, also in bGH Tg mice. These results suggest a major role for
      the Akt/Foxo1 pathway in the regulation of longevity in rodents. An activated
      gluconeogenic pathway and increased fat metabolism may be involved in mediating
      the effects of reduced somatotropic and insulin signaling on longevity. These
      results also add to the evidence that targeted disruption of the GH receptor/GH
      binding protein gene and CR act via overlapping, but distinct, mechanisms.

PMID- 15498883
TI  - Altered pharmacokinetics of 1alpha,25-dihydroxyvitamin D3 and 25-hydroxyvitamin
      D3 in the blood and tissues of the 25-hydroxyvitamin D-24-hydroxylase (Cyp24a1)
      null mouse.
AB  - The 25-hydroxyvitamin D-24-hydroxylase (CYP24A1) plays an important role in
      regulating concentrations of both the precursor 25-hydroxyvitamin D3 [25(OH)D3]
      and the hormone 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)(2)D3]. Previous
      studies suggest that Cyp24a1-null mice cannot clear exogenous 1alpha,25(OH)2D3
      efficiently. Here, we examined the metabolic clearance in Cyp24a1-null mice in
      vivo and in vitro using a physiological dose of [1beta-3H]1alpha,25(OH)2D3 or
      [26,27-methyl-3H]25(OH)D3. Cyp24a1-null mice showed difficulty in eliminating
      [1beta-3H]1alpha,25(OH)2D3 from the bloodstream and tissues over a 96-h time
      course, whereas heterozygotic mice eliminated the hormone within 6-12 h, although
      there was clearance of labeled hormone into water-soluble products involving
      liver in both genotypes. RT-PCR showed that Cyp24a1-null mice have decreased
      expression of 25-hydroxyvitamin D-1alpha-hydroxylase that must play a role in
      their survival. After the administration of [26,27-methyl-3H]25(OH)D3, Cyp24a1
      null mice showed higher [26,27-methyl-3H]25(OH)D3 levels and no [26,27-methyl
      3H]24,25(OH)2D3 formation, whereas heterozygotic mice showed significant [26,27
      methyl-3H]24,25(OH)2D3 production. Based upon in vitro experiments, keratinocytes
      from Cyp24a1-null mice fail to synthesize [1beta-3H]calcitroic acid from [1beta
      3H]1alpha,25(OH2D3 or [26,27-methyl-3H]24,25(OH)2D3 from [26,27-methyl
      3H]25(OH)D3 as do control mice, confirming the target cell catabolic role of
      CYP24A1 in these processes. Finally, the role of vitamin D receptor (VDR) in the
      vitamin D catabolic cascade was examined using VDR-null mice. Keratinocytes from
      VDR-null mice failed to metabolize [1beta-3H]1alpha,25(OH)2D3 confirming the
      importance of vitamin D-inducible, VDR-mediated, C24 oxidation pathway in target
      cells. These results suggest that the absence of CYP24A1 or VDR retards
      catabolism of 1alpha,25(OH)2D3 and 25(OH)D3, reinforcing the physiological
      importance of CYP24A1 in vitamin D homeostasis.

PMID- 15498884
TI  - Structural determinants for g protein activation and selectivity in the second
      intracellular loop of the thyrotropin receptor.
AB  - The TSH receptor (TSHR) activates mainly two signal transduction pathways, cAMP
      production and phosphoinositide turnover, mediated by Gs and Gq coupling,
      respectively. Several activating deletion and point mutations within
      intracellular loop 3 (ICL3) and the adjacent portion of transmembrane domain 6
      (TM6) support a direct G protein activation by this receptor domain. The ICL3,
      however, is predicted by modeling to interact with other receptor domains,
      primarily ICL2, to form a pocket for G protein binding and to allow optimum
      interaction. Systematic mutagenesis was used to identify important sites within
      ICL2 and potential interactions between ICL2 and ICL3 of the TSHR required for G
      protein coupling. Deletions of four or five residues and their corresponding
      multiple alanine substitutions were introduced into ICL2. Residues I523-D530,
      comprising mainly the N-terminal half of ICL2, appeared to be critical for Gs-
      and Gq-mediated signaling. A single alanine substitution screening within ICL2
      revealed hydrophobic residue M527 in particular and, to lesser extents, F525,
      R528, L529, and D530 as residues that selectively abolished or strongly impaired
      Gq activation. Molecular modeling suggests that F525 interacts with ICL3. To test
      this hypothesis, ICL2/ICL3 double mutants introducing strong complementary
      properties were constructed and tested for functional rescue of Gq-mediated
      signaling. Our results indicate that ICL2 interacts with ICL3 in close vicinity
      to F525 and T607, suggesting a conformational cooperation between ICL2 and ICL3
      during Gq activation by TSHR.

PMID- 15498885
TI  - Differential regulation of leptin synthesis in rats during short-term hypoxia and
      short-term carbon monoxide inhalation.
AB  - Leptin is a circulating hormone that is secreted primarily by adipose tissue.
      However, recent studies have demonstrated leptin production by other tissues,
      including placenta, stomach, kidney, liver, and lung, a process not only
      activated by stimuli such as insulin or corticosteroids, but also by hypoxia,
      which is mediated by the hypoxia inducible factor-1. In contrast to this fact,
      smokers have lower plasma leptin levels. The purpose of this study was to
      determine whether tissue hypoxygenation [induced by lack of oxygen] or inhalation
      of carbon monoxide (CO) are sufficient to up-regulate leptin in fat cells as well
      as in peripheral organs such as lung, liver, and kidney of rats. In hypoxic rats,
      leptin expression was unchanged or even reduced in adipose tissue. In contrast,
      in liver, kidney, and lung we observed an increase in leptin expression compared
      with normoxic controls, whereas plasma levels were unchanged. When animals were
      exposed to CO, generating a functional anemia known to activate the HIF-1
      dependent transcription, a significant decrease in leptin gene expression in
      adipose tissue and in all organs tested was observed. Plasma leptin
      concentrations after CO exposure were significantly diminished compared with
      those in control animals. These findings suggest that tissue hypoxygenation up
      regulates leptin expression in nonadipose tissue. However, this is not sufficient
      to raise plasma leptin levels in rats. Inhalation of CO leads to a significant
      decrease in leptin mRNA and protein concentration in the plasma of the animals,
      suggesting a negative effect of CO on leptin transcription.

PMID- 15498886
TI  - Bisphenol-A, an environmental contaminant that acts as a thyroid hormone receptor
      antagonist in vitro, increases serum thyroxine, and alters RC3/neurogranin
      expression in the developing rat brain.
AB  - Considering the importance of thyroid hormone (TH) in brain development, it is of
      potential concern that a wide variety of environmental chemicals can interfere
      with thyroid function or, perhaps of greater concern, with TH action at its
      receptor (TR). Recently bisphenol-A (BPA, 4,4' isopropylidenediphenol) was
      reported to bind to the rat TR and act as an antagonist in vitro. BPA is a high
      production volume chemical, with more than 800 million kg of BPA produced
      annually in the United States alone. It is detectable in serum of pregnant women
      and cord serum taken at birth; is 5-fold higher in amniotic fluid at 15-18 wk
      gestation, compared with maternal serum; and was found in concentrations of up to
      100 ng/g in placenta. Thus, the human population is widely exposed to BPA and it
      appears to accumulate in the fetus. We now report that dietary exposure to BPA of
      Sprague Dawley rats during pregnancy and lactation causes an increase in serum
      total T4 in pups on postnatal d 15, but serum TSH was not different from
      controls. The expression of the TH-responsive gene RC3/neurogranin, measured by
      in situ hybridization, was significantly up-regulated by BPA in the dentate
      gyrus. These findings suggest that BPA acts as a TH antagonist on the beta-TR,
      which mediates the negative feedback effect of TH on the pituitary gland, but
      that BPA is less effective at antagonizing TH on the alpha-TR, leaving TRalpha
      mediated events to respond to elevated T4.

PMID- 15498887
TI  - C75 alters central and peripheral gene expression to reduce food intake and
      increase energy expenditure.
AB  - C75, a synthetic inhibitor of fatty acid synthase (FAS), causes anorexia and
      profound weight loss in lean and genetically obese mice. C75 also acts as a
      stimulator of carnitine palmitoyltransferase-1 to induce fatty acid oxidation. To
      approximate human obesity, we used a 2-wk C75 treatment model for diet-induced
      obese (DIO) mice to investigate the central and peripheral effects of C75 on gene
      expression. C75 treatment decreased food intake, increased energy expenditure,
      and reduced body weight more effectively in DIO than in lean mice. Analysis of
      the gene expression changes in hypothalamus demonstrated that the reduced food
      intake in C75-treated DIO mice might be mediated by inhibition of orexigenic
      neuropeptide expression and induction of anorexigenic neuropeptide expression.
      Gene expression changes in peripheral tissues indicated that C75 increased energy
      expenditure by the induction of genes involved in fatty acid oxidation. C75 also
      inhibited the expression of genes in peripheral tissues responsible for fatty
      acid synthesis and accumulation. The patterns of the changes in central and
      peripheral gene expression that occur with C75 treatment provide mechanisms to
      explain the reduced food intake and increased energy expenditure observed with
      C75.

PMID- 15498888
TI  - Dramatic decrease of innervation density in bone after ovariectomy.
AB  - Recent studies have demonstrated that bone is highly innervated and contains
      neuromediators that have functional receptors on bone cells. However, no data
      exist concerning the quantitative changes of innervation during bone loss
      associated with estrogen withdrawal. To study the involvement of nerve fibers in
      the regulation of bone remodeling, we have evaluated the modifications of
      innervation in a classical in vivo model of osteopenia in rats, ovariectomy
      (OVX). Skeletal innervation was studied by immunocytochemistry using antibodies
      directed against specific neuronal markers, neurofilament 200 and synaptophysin,
      and the neuromediator glutamate. Sciatic neurectomy, another model of bone loss
      due to limb denervation and paralysis, was used to validate our quantitative
      image analysis technique of immunostaining for nerve markers. Female Wistar rats
      at 12 wk of age were sham-operated (SHAM) or ovariectomized (OVX). Bone mineral
      density measurement and bone histomorphometry analysis of tibiae 14 d after
      surgery demonstrated a significant bone loss in OVX compared with SHAM. We
      observed an important reduction of nerve profile density in tibiae of OVX animals
      compared with SHAM animals, whereas innervation density in skin and muscles was
      similar for OVX and control rats. Quantitative image analysis of immunostainings
      demonstrated a significant decrease of the percentage of immunolabeling per total
      bone volume of neurofilament 200, synaptophysin, and glutamate in both the
      primary and secondary spongiosa of OVX rats compared with SHAM. These data
      indicate for the first time that OVX-induced bone loss in rat tibiae is
      associated with a reduction in nerve profile density, suggesting a functional
      link between the nervous system and the bone loss after ovariectomy.

PMID- 15498889
TI  - The human 3beta-hydroxysteroid dehydrogenase/Delta5-Delta4 isomerase type 2
      promoter is a novel target for the immediate early orphan nuclear receptor Nur77
      in steroidogenic cells.
AB  - The human (h) 3beta-hydroxysteroid dehydrogenase/Delta5-Delta4 isomerase type 2
      (3beta-HSD2) enzyme, encoded by the hHSD3B2 gene, is mainly found in gonads and
      adrenals. This enzyme catalyzes an essential early step in the biosynthesis of
      all classes of steroid hormones. The critical nature of the enzyme is supported
      by the occurrence of human syndromes that are associated with insufficient 3beta
      HSD2 expression and/or activity. Although the need for a functional 3beta-HSD2
      enzyme is indisputable, the molecular mechanisms that regulate HSD3B2 expression
      (both basal and hormone-induced) in steroidogenic cells remain poorly understood.
      A role for the Nur77 family of immediate-early orphan nuclear receptors in
      steroidogenesis has received recent interest. For example, Nur77 is present in
      gonads and adrenals, where its expression is robustly and rapidly induced by
      hormones that stimulate steroidogenic gene expression. Moreover, the expression
      patterns of Nur77 and at least one key steroidogenic gene (hHSD3B2) closely
      parallel one another. We now report that the hHSD3B2 promoter is indeed a novel
      target for Nur77 in both testicular Leydig cells and adrenal cells. We have
      mapped a novel response element located at -130 bp specific for Nur77 and not
      other orphan nuclear receptors (steroidogenic factor-1 and liver receptor homolog
      1) previously shown to regulate hHSD3B2 promoter activity. This Nur77 element is
      essential and sufficient to confer Nur77 responsiveness to the hHSD3B2 promoter,
      and its mutation blunts basal and hormone-induced hHSD3B2 promoter activity in
      steroidogenic cells. We also show that Nur77 synergizes with all members of the
      steroid receptor coactivator family of coactivators on the hHSD3B2 promoter.
      Taken together, our identification of Nur77 as an important regulator of HSD3B2
      promoter activity helps us to better define the tissue-specific and hormonal
      regulation of the HSD3B2 gene in steroidogenic cells.

PMID- 15498890
TI  - Extracellularly regulated kinases 1/2 (p44/42 mitogen-activated protein kinases)
      phosphorylate synapsin I and regulate insulin secretion in the MIN6 beta-cell
      line and islets of Langerhans.
AB  - The p44/p42 MAPKs (ERK1/2) cascade regulates beta-cell nuclear events, which
      modulates cell differentiation and gene transcription, whereas its implication in
      processes occurring in the cytoplasm, such as activation of the exocytotic
      machinery, is still unclear. Using the MIN6 beta-cell line and isolated rat
      islets of Langerhans, we investigated whether glucose, by activating the ERK1/2
      cascade, induces phosphorylation of cytoplasmic proteins implicated in exocytosis
      of insulin granules such as synapsin I. We observed that the majority of ERK1/2
      activity induced by glucose remains in the cytoplasm and physically interacts
      with synapsin I, allowing phosphorylation of the substrate. Therefore, we
      reexamined the potential requirement of ERK1/2 for insulin secretion. Blocking
      activation of ERK1/2 using MEK1/2, the MAPK kinase inhibitor PD98059 or using
      small interfering RNA-mediated silencing of ERK1 and ERK2 expressions resulted in
      partial inhibition of glucose-induced insulin release, indicating that ERK1/2
      pathway participates also in the regulation of insulin secretion. Moreover, using
      the pancreatic islet perifusion model, we found that the ERK1/2 activity
      participates in the first and second phases of insulin release induced by
      glucose. Taken together, our results demonstrate new aspects of the glucose
      dependent actions of ERK1/2 in beta-cells exerted on cytoplasmic proteins,
      including synapsin I, and participating in the overall glucose-induced insulin
      secretion.

PMID- 15498891
TI  - The extent to which relaxin promotes proliferation and inhibits apoptosis of
      cervical epithelial and stromal cells is greatest during late pregnancy in rats.
AB  - Relaxin promotes marked growth of the cervix during the second half of rat
      pregnancy, and this growth is accompanied by an increase in both epithelial and
      stromal cells. The objective of this study was to test the hypothesis that the
      extent to which relaxin promotes proliferation and inhibits apoptosis of cervical
      cells is greatest during late pregnancy in rats. The influence of neutralization
      of circulating relaxin by iv injection of 5 mg monoclonal antibody against rat
      relaxin (MCA1) was examined at 3-d intervals throughout the second half of
      pregnancy. Controls were injected with either 5 mg monoclonal antibody against
      fluorescein or 0.5 ml PBS vehicle. To evaluate cell proliferation, 5'-bromo-2
      deoxyuridine was injected sc 8 h before cervixes were collected. Terminal
      deoxynucleotidyl transferase-mediated deoxyuridine 5'-triphosphate nick end
      labeling and electron microscopy were used to detect apoptotic cells.
      Neutralization of relaxin with MCA1 decreased the rate of proliferation and
      increased the rate of apoptosis of cervical cells by d 13. However, the extent to
      which relaxin influenced these processes was greatest and dramatic by late
      pregnancy. In MCA1-treated rats on d 22 of pregnancy, the rates of proliferation
      of both epithelial and stromal cells were less than 20% those in controls, and
      the rates of apoptosis in epithelial cells and stromal cells were more than 10-
      and 3-fold, respectively, greater than those in controls. In conclusion, this
      study provides evidence that the extent to which relaxin promotes proliferation
      and inhibits apoptosis of cervical epithelial and stromal cells is greatest
      during late pregnancy.

PMID- 15498892
TI  - Design principle of gene expression used by human stem cells: implication for
      pluripotency.
AB  - Human embryonic stem cells (ESC) are undifferentiated and are endowed with the
      capacities of self-renewal and pluripotential differentiation. Adult stem cells
      renew their own tissue, but whether they can transdifferentiate to other tissues
      is still controversial. To understand the genetic program that underlies the
      pluripotency of stem cells, we compared the transcription profile of ESC with
      that of progenitor/stem cells of human hematopoietic and keratinocytic origins,
      along with their mature cells to be viewed as snapshots along tissue
      differentiation. ESC gene profiles show higher complexity with significantly more
      highly expressed genes than adult cells. We hypothesize that ESC use a strategy
      of expressing genes that represent various differentiation pathways and selection
      of only a few for continuous expression upon differentiation to a particular
      target. Such a strategy may be necessary for the pluripotency of ESC. The
      progenitors of either hematopoietic or keratinocytic cells also follow the same
      design principle. Using advanced clustering, we show that many of the ESC
      expressed genes are turned off in the progenitors/stem cells followed by a
      further down-regulation in adult tissues. Concomitantly, genes specific to the
      target tissue are up-regulated toward mature cells of skin or blood.

PMID- 15498894
TI  - Transmural stretch-dependent regulation of contractile properties in rat heart
      and its alteration after myocardial infarction.
AB  - The "stretch-sensitization" response is essential to the regulation of heart
      contractility. An increase in diastolic volume improves systolic contraction. The
      cellular mechanisms of this modulation, the Frank-Starling law, are still
      uncertain. Moreover, their alterations in heart failure remains controversial.
      Here, using left ventricular skinned rat myocytes, we show a nonuniform stretch
      sensitization of myofilament activation across the ventricular wall. Stretch
      dependent Ca2+ sensitization of myofilaments increases from sub-epicardium to sub
      endocardium and is correlated with an increase in passive tension. This passive
      tension-dependent component of myofibrillar activation is not associated with
      expression of titin isoforms, changes in troponin I level, and phosphorylation
      status. Instead, we observe that stretch induces phosphorylation of ventricular
      myosin light chain 2 isoform (VLC2b) in sub-endocardium specifically. Thus, VLC2b
      phosphorylation could act as a stretch-dependent modulator of activation tuned
      within normal heart. Moreover, in postmyocardial infarcted rat, the gradient of
      stretch-dependent Ca2+ sensitization disappears associated with a lack of VLC2b
      phosphorylation in sub-endocardium. In conclusion, nonuniformity is a major
      characteristic of the normal adult left ventricle (LV). The heterogeneous
      myocardial deformation pattern might be caused not only by the morphological
      heterogeneity of the tissue in the LV wall, but also by the nonuniform
      contractile properties of the myocytes across the wall. The loss of a contractile
      transmural gradient after myocardial infarction should contribute to the impaired
      LV function.

PMID- 15498893
TI  - Multidrug resistance-1 (MDR-1): a new target for T cell-based immunotherapy.
AB  - Acquired multidrug resistance (MDR) remains a major challenge in the treatment of
      cancer with chemotherapeutic drugs. It can be mediated by the up-regulated
      expression of different proteins within the tumor cell membrane. Here, we used
      murine multidrug resistance-1 (MDR-1) as a target-antigen for the immunotherapy
      of cancer. We successfully demonstrated that peripheral T cell tolerance can be
      broken by oral administration of a DNA vaccine encoding MDR-1 and carried by
      attenuated Salmonella typhimurium to secondary lymphoid organs. Thus, mice,
      immunized orally three times at 2-wk intervals and challenged 2 wk thereafter
      with either MDR-1 expressing CT-26 colon carcinoma cells or MDR-1 expressing
      Lewis lung carcinoma cells, revealed a significant increase in life span. This
      was evident, when compared with animals either vaccinated with the empty control
      vector or challenged with the parental cell lines lacking overexpression of MDR
      1. The immune response induced was antigen-specific and CD8+ T cell-mediated. The
      presence of the target antigen led to up-regulation of activation markers on CD8+
      T cells and resulted in a strong cytotoxic T cell response as well as lysis of
      tumor target cells in vitro. We furthermore established the vaccine to be an
      effective treatment for established multi-drug-resistant tumor metastases,
      resulting in a significantly increased life span of experimental animals. Absence
      of CD8+ T cells due to in vivo depletion led to abrogation of effectiveness.
      Taken together, our results demonstrate that T cell tolerance against the MDR-1
      self-antigen can be broken. It is anticipated that the combination of such an
      approach with chemotherapy could lead to more effective treatments of cancer.

PMID- 15498895
TI  - Malignant versus benign nodules at CT screening for lung cancer: comparison of
      thin-section CT findings.
AB  - PURPOSE: To evaluate thin-section computed tomographic (CT) characteristics of
      malignant nodules on the basis of overall appearance (pure ground-glass opacity
      [GGO], mixed GGO, or solid opacity) in comparison with the appearance of benign
      nodules. MATERIALS AND METHODS: Institutional review board approval and patient
      consent were obtained. Follow-up diagnostic CT was performed in 747 suspicious
      pulmonary nodules detected at low-dose CT screening (17 892 examinations). Of 747
      nodules, 222 were evaluated at thin-section CT (1-mm collimation), which included
      59 cancers and 163 benign nodules (3-20 mm). Thin-section CT findings of
      malignant versus benign nodules with pure GGO (17 vs 12 lesions), mixed GGO (27
      vs 29 lesions), or solid opacity (15 vs 122 lesions) were analyzed. Fisher exact
      test for independence was used to compare differences in shape, margin, and
      internal features between benign and malignant nodules. Positive predictive value
      (PPV) was analyzed when a category was significantly different from the others.
      RESULTS: Among nodules with pure GGO, a round shape was found more frequently in
      malignant lesions (11 of 17, 65%) than in benign lesions (two of 12, 17%; P =
      .02; PPV, 85%); mixed GGO, a subtype with GGO in the periphery and a high
      attenuation zone in the center, was seen much more often in malignant lesions (11
      of 27, 41%) than in benign lesions (two of 29, 7%; P = .004; PPV, 85%). Among
      solid nodules, a polygonal shape or a smooth or somewhat smooth margin was
      present less frequently in malignant than in benign lesions (polygonal shape: 7%
      vs 38%, P = .02; smooth or somewhat smooth margin: 0% vs 63%, P < .001), and 98%
      (46 of 47) of polygonal nodules and 100% (77 of 77) of nodules with a smooth or
      somewhat smooth margin were benign. CONCLUSION: Recognition of certain
      characteristics at thin-section CT can be helpful in differentiating small
      malignant nodules from benign nodules.

PMID- 15498896
TI  - Techniques and applications of automatic tube current modulation for CT.
AB  - Introduction of slip-ring technology with subsequent development of single- and
      multi-detector row helical computed tomographic (CT) scanners have expanded the
      applications of CT, leading to a substantial increase in the number of CT
      examinations being performed. Owing to concerns about the resultant increase in
      associated radiation dose, many technical innovations have been introduced. One
      such innovation is automatic tube current modulation. The purpose of automatic
      tube current modulation is to maintain constant image quality regardless of
      patient attenuation characteristics, thus allowing radiation dose to patients to
      be reduced. This review discusses the principles, clinical use, and limitations
      of different automatic tube current modulation techniques.

PMID- 15498897
TI  - Osteoid osteoma: factors for increased risk of unsuccessful thermal coagulation.
AB  - PURPOSE: To retrospectively identify risk factors that may impede a favorable
      clinical outcome after thermocoagulation for osteoid osteoma. MATERIALS AND
      METHODS: Informed consent (permission for the procedure and permission to use
      patient data for analysis) was obtained from all patients who met study criteria,
      and institutional review board did not require approval. Analysis included age,
      sex, size and location of osteoid osteoma, presence of calcified nidus, number of
      needle positions used for coagulation, coagulation time, accuracy of needle
      position, learning curve of radiologist, and previous treatment in 95 consecutive
      patients with osteoid osteoma treated with thermocoagulation. With chi(2)
      analysis, Fisher exact test, or unpaired Student t test and logistic regression
      analysis, 23 unsuccessfully treated patients were compared with 72 successfully
      (pain-free) treated patients. RESULTS: Parameters associated with decreased risk
      for treatment failure were advanced age (mean age, 24 years in treatment success
      group vs 20 years in treatment failure group) and increased number of needle
      positions during thermocoagulation. Estimated odds ratios were, respectively,
      0.93 (95% confidence interval: 0.88, 0.99) and 0.10 (95% confidence interval:
      0.02, 0.41). Patients with a lesion of 10 mm or larger seemed at risk for
      treatment failure (odds ratio = 2.68), but the 95% confidence interval of 0.84 to
      8.52 included the 1.00 value. Needle position was inaccurate in nine of 23
      patients with treatment failure; only one needle position was used in eight of
      these nine patients. Lesion location, calcification, sex, coagulation time,
      radiologist's learning curve, and previous treatment were not risk factors.
      CONCLUSION: Multiple needle positions reduce the risk of treatment failure in all
      patients and should especially, but not exclusively, be used in large (> or =10
      mm) lesions or lesions that are difficult to engage to reduce the risk for
      unsuccessful treatment.

PMID- 15498898
TI  - Primary angiitis of the central nervous system at conventional angiography.
AB  - PURPOSE: To retrospectively determine the sensitivity and specificity of cerebral
      angiography for the diagnosis of primary angiitis of the central nervous system
      (CNS). MATERIALS AND METHODS: Institutional review board approval was obtained,
      and informed consent was not required. Thirty-eight patients (13 men, 25 women;
      mean age, 55 years) had undergone cerebral angiography followed by cortical and
      leptomeningeal biopsy for possible primary angiitis of the CNS during an 8-year
      period. Angiography reports were reviewed by investigators blinded to the results
      of biopsy. Angiographic findings were categorized as typical for vasculitis,
      normal, or other. Sensitivity and specificity of cerebral angiography for the
      diagnosis of primary angiitis of the CNS were calculated. RESULTS: Fourteen
      patients had typical angiographic findings of vasculitis. None had primary
      angiitis of the CNS at brain biopsy (60% specificity). Specific pathologic
      diagnoses other than primary angiitis of the CNS were made in six patients.
      Findings of brain biopsy in the remaining eight patients were nondiagnostic.
      Repeat angiograms were obtained in three of the eight patients. One patient
      demonstrated interval improvement in multiple focal intracranial arterial
      stenoses and two demonstrated worsening. Primary angiitis of the CNS was found at
      biopsy in two of the remaining 24 patients (0% sensitivity). One of the two
      patients had slow filling of a single distal cortical artery, and the other
      patient had multiple regions of abnormally prolonged capillary blush. CONCLUSION:
      In this series, patients suspected of having primary angiitis of the CNS on the
      basis of clinical and angiographic findings did not have primary angiitis of the
      CNS at biopsy. Typical angiographic findings of primary angiitis of the CNS are
      often associated with other specific pathologic diagnoses, which emphasizes the
      importance of brain biopsy.

PMID- 15498899
TI  - Visualization of stroke with clinical MR imagers in rats: a feasibility study.
AB  - This experiment was conducted in compliance with the guidelines of the
      International Committee on Thrombosis and Hemostasis and the current
      institutional regulations for use and care of laboratory animals. The purpose of
      the present study was to report the feasibility of using clinical magnetic
      resonance (MR) imaging devices for depiction of stroke in a rat model. Twenty
      four rats with photochemically induced thrombosis of the middle cerebral artery
      were examined at superacute (1 hour, n = 24), acute (12 hours, n = 12), and
      subacute (24 hours, n = 12) phases with 1.5-T MR imaging weighted for T1, T2,
      diffusion, and gadopentetate dimeglumine-enhanced perfusion. With reasonable
      signal-to-noise ratio and imaging times, ischemic lesions were well distinguished
      on MR images as validated qualitatively and quantitatively with postmortem
      standard-of-reference techniques, including volume-rendered computed tomography,
      microangiography, and histochemistry. In the superacute phase, the perfusion
      defect at perfusion-weighted MR imaging was well matched with microangiographic
      and pathologic findings (P > .05). There was no difference in lesion size at
      perfusion-weighted MR imaging between superacute and subacute phases (P > .05).
      Performance of certain stroke-related research in rats is feasible with clinical
      MR imagers.

PMID- 15498900
TI  - Catheter visualization with resonant markers at MR imaging-guided deployment of
      endovascular stents in swine.
AB  - PURPOSE: To evaluate resonant circuits as markers for magnetic resonance (MR)
      imaging-guided placement of nitinol stents. MATERIALS AND METHODS: The study was
      approved by the institutional animal research committee and complied with
      National Institutes of Health guidelines for care and use of laboratory animals.
      Resonant circuits similar to catheter markers used at conventional angiography
      were placed proximally and distally to a nitinol stent in a stent delivery
      system. Resonant circuits were tested in vitro and in vivo for signal intensity
      levels that would enable visualization during MR imaging-guided stent deployment.
      Experiments were conducted by using real-time imaging with a 1.5-T unit. Stents
      (n = 9) were deployed in the vena cava (n = 2), abdominal aorta (n = 2), isthmus
      of the aorta (n = 2), and carotid (n = 2) and iliac (n = 1) arteries in five
      pigs. After intervention, the site of the stent was investigated with balanced
      fast field-echo MR imaging and contrast material-enhanced MR angiography. Blood
      flow velocities were measured in the stent lumen and next to the stent with
      velocity-encoded cine MR imaging. Level of agreement was determined with Bland
      Altman analysis. RESULTS: During all interventions, resonant circuits provided
      highly visible MR signal that allowed fast and reliable visualization of the
      stent delivery system. Borders of loaded stents were clearly marked, which
      allowed precise stent placement in all experiments. Balanced fast field-echo MR
      imaging and contrast-enhanced MR angiography provided information about immediate
      postintervention position. Positions depicted on MR images were found accurate at
      postmortem examination. Results of Bland-Altman analysis showed good agreement
      between blood flow velocities measured in and next to the stent lumen, with a
      mean difference of -9 cm/sec +/- 5 (standard deviation). CONCLUSION: Resonant
      circuits are well suited for use at deployment of endovascular stents.

PMID- 15498901
TI  - Clinical examination, endosonography, and MR imaging in preoperative assessment
      of fistula in ano: comparison with outcome-based reference standard.
AB  - PURPOSE: To prospectively evaluate the relative accuracy of digital examination,
      anal endosonography, and magnetic resonance (MR) imaging for preoperative
      assessment of fistula in ano by comparison to an outcome-derived reference
      standard. MATERIALS AND METHODS: Ethical committee approval and informed consent
      were obtained. A total of 104 patients who were suspected of having fistula in
      ano underwent preoperative digital examination, 10-MHz anal endosonography, and
      body-coil MR imaging. Fistula classification was determined with each modality,
      with reviewers blinded to findings of other assessments. For fistula
      classification, an outcome-derived reference standard was based on a combination
      of subsequent surgical and MR imaging findings and clinical outcome after
      surgery. The proportion of patients correctly classified and agreement between
      the preoperative assessment and reference standard were determined with trend
      tests and kappa statistics, respectively. RESULTS: There was a significant linear
      trend (P < .001) in the proportion of fistula tracks (n = 108) correctly
      classified with each modality, as follows: clinical examination, 66 (61%)
      patients; endosonography, 87 (81%) patients; MR imaging, 97 (90%) patients.
      Similar trends were found for the correct anatomic classification of abscesses (P
      < .001), horseshoe extensions (P = .003), and internal openings (n = 99, P <
      .001); endosonography was used to correctly identify the internal opening in 90
      (91%) patients versus 96 (97%) patients with MR imaging. Agreement between the
      outcome-derived reference standard and digital examination, endosonography, and
      MR imaging for classification of the primary track was fair (kappa = 0.38), good
      (kappa = 0.68), and very good (kappa = 0.84), respectively, and fair (kappa =
      0.29), good (kappa = 0.64), and very good (kappa = 0.88), respectively, for
      classification of abscesses and horseshoe extensions combined. CONCLUSION:
      Endosonography with a high-frequency transducer is superior to digital
      examination for the preoperative classification of fistula in ano. While MR
      imaging remains superior in all respects, endosonography is a viable alternative
      for identification of the internal opening.

PMID- 15498902
TI  - Repeatability of motor and working-memory tasks in healthy older volunteers:
      assessment at functional MR imaging.
AB  - PURPOSE: To prospectively determine the repeatability of functional magnetic
      resonance (MR) imaging brain activation tasks in a group of healthy older male
      volunteers. MATERIALS AND METHODS: Local research ethics committee approval and
      informed consent were obtained. Sixteen men with a mean age of 69 years +/- 3
      (standard deviation) performed finger-tapping and N-back (number of screens back)
      working-memory tasks. Each subject underwent MR imaging three times in weekly
      intervals. Within-subject task repeatability was analyzed in terms of the number
      of voxels classified as activated (activation extent), the mean activation
      amplitude, and (for finger tapping) the center of the mass of the activated
      region. A repeatability index was calculated to compare test-retest repeatability
      between subjects and between functional MR imaging tasks. Within-session, between
      session, and between-subject variability was assessed by using analysis of
      variance testing of activation amplitude and extent. RESULTS: Nine of the 16
      subjects generated useful data at all three MR imaging-functional task sessions.
      At single-subject, single-session analysis, cortical activation was identified in
      most subjects and at most sessions. The centers of the masses of motor cortex
      activation were highly reproducible (within 3 mm). Patterns of activation were
      qualitatively repeatable, but there was substantial variability in the amplitudes
      and extents of activated regions. Within-session coefficients of variation (CVs)
      for left- versus right-hand and right- versus left-hand finger tapping were,
      respectively, 65% and 43% for activation amplitude and 75% and 121% for
      activation extent. The between-session CVs for activation amplitude were similar
      to the within-session values, whereas between-session CVs for activation extent
      were much greater than within-session values, up to 206%. CONCLUSION: The
      generally poor quantitative task repeatability highlights the need for further
      methodologic developments before much reliance can be placed on functional MR
      imaging results of single-session experiments.

PMID- 15498903
TI  - Prostate cancer: evaluation of vascular characteristics with dynamic contrast
      enhanced T1-weighted MR imaging--initial experience.
AB  - PURPOSE: To use contrast material-enhanced magnetic resonance (MR) imaging and a
      distributed-parameter tracer kinetics model for prospectively evaluating the
      vascular characteristics of prostate cancer. MATERIALS AND METHODS: Twenty-two
      patients between 57 and 76 years of age (mean age, 67 years) with histologically
      proved adenocarcinoma of the prostate were examined by using three-dimensional
      dynamic contrast-enhanced T1-weighted MR imaging at 1.5 T. The local research
      ethics committee approved this study, and written consent was obtained from all
      patients. Data from regions of interest drawn in tumor, normal-appearing
      peripheral zone tissue, and muscle were analyzed to provide estimates of
      perfusion, blood volume, interstitial volume, and microvascular permeability
      surface area product. These estimates were compared by using the nonparametric
      Wilcoxon signed rank test. RESULTS: Mean blood flow was significantly (P < .001)
      higher in 22 prostate tumors than in 20 contralateral peripheral zones (66 vs 32
      mL/100 mL/min). Similarly, the interstitial distribution volume in tumors was
      enlarged compared with the interstitial distribution volume in normal peripheral
      zones (42 vs 27 mL/100 mL). Blood volume and microvascular permeability-surface
      area product values in tumors (1.0 mL/100 mL and 22 mL/100 mL/min, respectively)
      were similar to estimated values in peripheral zone tissue (1.5 mL/100 mL and 21
      mL/100 mL/min, respectively). CONCLUSION: These findings show considerable
      promise for isolating vascular characteristics of prostate cancer.

PMID- 15498905
TI  - Intraoperative ultrasonography: history, current state of the art, and future
      directions.

PMID- 15498906
TI  - Polypoid adenomyomas: sonohysterographic and color Doppler findings with
      histopathologic correlation.
AB  - OBJECTIVE: This study was undertaken to describe the sonographic features of
      polypoid adenomyomas of the uterus and to determine the diagnostic role of
      sonohysterography and color Doppler sonography in the evaluation of these
      lesions. METHODS: The sonographic findings for 46 histologically proved cases of
      polypoid adenomyomas of the uterus, accumulated over 10 years, were reviewed
      retrospectively. The pathologic diagnoses included typical polypoid adenomyoma (n
      = 36), atypical polypoid adenomyoma (n = 7), and low-grade adenosarcoma arising
      in polypoid adenomyoma (n = 3). RESULTS: Of 46 total uterine tumors, 31 were in
      the corpus, 12 were in the fundus, and 3 were in the isthmus. The mean tumor size
      was 3.5 cm (range, 0.5-9 cm). The tumors were polypoid in 30 cases, pedunculated
      in 11 cases, and sessile in the remaining 5 cases. Of the pedunculated tumors, 5
      protruded into the endocervical canal and 2 had prolapsed into the vagina. Three
      distinct sonographic patterns were identified with respect to the presence of
      cystic areas: a solid mass (pattern 1) in 12 cases, a solid mass with cystic
      areas (pattern 2) in 32 cases, and a predominantly cystic mass (pattern 3) in 2
      cases. The characteristic sonographic features of polypoid adenomyomas included
      heterogeneous or homogeneous isoechogenicity relative to the myometrium, a smooth
      surface, a poorly defined margin with the underlying myometrium, hemorrhagic
      foci, posterior shadowing, a single vascular pedicle entering the mass, and
      associated adenomyosis in the myometrium. CONCLUSIONS: Knowledge of the
      sonographic appearance of polypoid adenomyomas may facilitate diagnosis and may
      help distinguish these tumors from other polypoid uterine tumors.

PMID- 15498907
TI  - The clinical value of 3-dimensional saline infusion sonography in addition to 2
      dimensional saline infusion sonography in women with abnormal uterine bleeding:
      work in progress.
AB  - OBJECTIVE: To evaluate the clinical relevance of 3-dimensional saline infusion
      sonography (3D-SIS) in addition to conventional SIS in women with abnormal
      uterine bleeding suspected of having intrauterine abnormalities. METHODS: All
      women suspected of having intrauterine abnormalities were eligible. Before 3D
      SIS, conventional SIS was performed. The results of these techniques were
      compared with the "combined method reference standard" (hysteroscopy, endometrial
      sampling, and clinical follow-up in cases with normal SIS findings). Diagnostic
      characteristics (with 95% confidence intervals [CIs]) of 3D-SIS and SIS were
      calculated as well as their respective accuracy in evaluating the histologic
      nature, the intrauterine extension, and the location of intrauterine
      abnormalities. Moreover, the reliability (kappa value) and clinical relevance of
      3D-SIS were assessed. RESULTS: A total of 49 women were included, and 4 women
      were excluded. The positive predictive values of 3D-SIS and SIS were,
      respectively, 1.00 and 0.86 (95% CI, 0.72-0.99; P = .15), and the diagnostic
      accuracy values were 0.98 (95% CI, 0.94-1.0) and 0.91 (95% CI, 0.83-0.99; P =
      .08). Saline infusion sonography and 3D-SIS were equally accurate in evaluating
      the histologic nature, intrauterine extent, and location of intrauterine
      abnormalities (respective kappa values: 0.85 versus 0.93; P = .88; 0.83 versus
      0.83; and 0.77 versus 0.80; P = .81). The reliability of 3D-SIS was good:
      intraobserver and interobserver agreement (kappa) were 0.78 and 0.72. Three women
      (6.7%) had the benefit of additional 3D-SIS: in these women, SIS wrongly led to a
      diagnosis of intrauterine abnormalities (P = .08). CONCLUSIONS: Three-dimensional
      saline infusion sonography is valid and reliable in women suspected of having
      intrauterine abnormalities and may indeed have relevant clinical value in
      addition to conventional SIS.

PMID- 15498908
TI  - Sonographic evaluation of the lower uterine segment in patients with previous
      cesarean delivery.
AB  - OBJECTIVE: To evaluate the appearance of the lower uterine segment (LUS) in
      pregnant women with previous cesarean delivery and to compare the LUS thickness
      with that in women with unscarred uteri. METHODS: In a prospective study,
      sonographic examination was performed on 53 pregnant women with previous cesarean
      delivery (cesarean group), 40 nulliparas (nullip-control), and 40 women who had 1
      or more childbirths with unscarred uteri (multip-control) between 36 and 38
      weeks' gestation to assess the appearance and compare the thickness of the LUS.
      In the cesarean group, the sonographic findings were correlated with the delivery
      outcome and the intraoperative LUS appearance. RESULTS: In the cesarean group, 44
      patients (83.0%) had a normal-appearing LUS indistinguishable from that of
      control groups; 2 patients (3.8%) had an LUS defect suggestive of dehiscence; and
      7 patients (13.2%) had thickened areas of increased echogenicity with or without
      myometrial thinning. Although the cesarean group had a thinner LUS (1.9 +/- 1.4
      mm) when compared with both the nullip-control group (2.3 +/- 1.1 mm; P > .05)
      and the multip-control group (3.4 +/- 2.2 mm; P < .001), only the latter
      difference achieved statistical significance. One of the 2 patients who had a
      sonographically suspected LUS defect had confirmed uterine dehiscence during
      surgery. An intraoperatively diagnosed paper-thin LUS, when compared with an LUS
      of normal thickness, had significantly smaller sonographic LUS measurements (1.1
      +/- 0.6 versus 2.0 +/- 0.8 mm, respectively; P = .004). CONCLUSIONS: Prior
      cesarean delivery is associated with a sonographically thinner LUS when compared
      with those with prior vaginal delivery. Prenatal sonographic examination is
      potentially capable of diagnosing a uterine defect and determining the degree of
      LUS thinning in patients with previous cesarean delivery.

PMID- 15498909
TI  - Association of amniotic fluid index with estimated fetal weight.
AB  - OBJECTIVE: The relationship between amniotic fluid volume and gestational age has
      been described previously. The association of body weight and urine output has
      been observed in human neonates. Our goal was to assess the correlation of the
      amniotic fluid index (AFI) with estimated fetal weight (EFW) in the third
      trimester. METHODS: We conducted a retrospective observational study on 426
      pregnant women with singleton gestations who were referred to our unit for
      sonographic evaluation in the third trimester. The AFI, EFW, and EFW percentile
      corrected for gestational age were evaluated. The sonographic examinations were
      stratified into 3 gestational age categories: 28 through 33.9 weeks, 34 through
      37.9 weeks, and 38 weeks and later. Maternal and fetal outcome variables were
      collected from medical records. Linear regression, Mann-Whitney U, and Kruskal
      Wallis tests were used for statistical analysis. RESULTS: There was no
      significant relationship between the AFI and EFW in the entire group of patients
      (R = 0.08; P = .096). There was a significant relationship between the AFI and
      EFW after 38 weeks' gestation (R = 0.30; P = .003). In addition, in female
      fetuses the EFW percentile correlated with higher AFI values at all gestational
      ages (R = 0.31; P < .001); this, however, was not observed in male fetuses.
      CONCLUSIONS: There is no relationship between the AFI and EFW during the third
      trimester, although a positive relationship between the AFI and EFW was noted
      late in gestation. In pregnancies with female fetuses, the AFI was positively
      associated with EFW percentile before 38 weeks' gestation.

PMID- 15498910
TI  - Risk for malignancy of thyroid nodules as assessed by sonographic criteria: the
      need for biopsy.
AB  - OBJECTIVE: To correlate sonographic and color Doppler characteristics of thyroid
      nodules with the results of sonographically guided fine-needle aspiration biopsy
      to establish the relative importance of these features in predicting risk for
      malignancy. METHODS: We retrospectively analyzed the sonographic features of 34
      malignant and 36 benign thyroid nodules with respect to size, echogenicity, echo
      structure, shape, border, calcification, and internal vascularity. Individual
      features and combinations of features were analyzed for their correlation with
      benign or malignant disease. A comparative analysis of several authors'
      previously proposed methods for distinguishing between benign and malignant
      nodules using sonographic criteria was also performed to determine their
      sensitivity and specificity in predicting nodule disease within our study data.
      RESULTS: Nodule size ranged from 0.8 to 4.6 cm in greatest dimension (mean, 1.96
      cm; SD, 0.877 cm). The prevalence of malignancy in our study population was
      estimated to be nearly 5.33%. Intragroup comparison of sonographic features among
      benign and malignant nodules resulted in identification of intrinsic
      calcification as the only statistically significant predictor of malignancy
      (35.3% sensitive and 94.4% specific; P < .005). Presence of a "snowstorm" pattern
      of calcification was 100% specific for malignancy. Echogenicity, echo structure,
      shape, border classification, and grade of internal vascularity did not show any
      significant difference between benign and malignant nodules in this study.
      Various combinations of features previously suggested to be significant
      predictors of malignancy were also analyzed and shown to have very little
      sensitivity or specificity in predicting benign or malignant disease among
      nodules in our study population. CONCLUSIONS: This study indicates that the
      presence of intrinsic microcalcification is the only statistically reliable
      criterion on which to base increased suspicion for malignancy in thyroid nodules.
      Our results indicate the need for biopsy in determining further workup. All
      nodules that show the presence of intrinsic microcalcification should undergo
      biopsy, particularly if calcifications have a snowstorm appearance on sonography.

PMID- 15498911
TI  - Display of 3-dimensional ultrasonographic images for interventional procedures:
      volume-rendered versus multiplanar display.
AB  - OBJECTIVE: The goal of this project was to assess the display of 3-dimensional
      ultrasonographic images as used for interventional procedures, particularly the
      conspicuity of various targets and interventional devices, comparing volume
      rendered (VR) versus multiplanar reformatted (MPR) display approaches. METHODS: A
      series of ultrasonographic phantoms were made from a petroleum gel with
      cornstarch used to vary the echo texture. Three-dimensional ultrasonographic
      target and device conspicuity were judged with a 5-point visual rating scale. The
      MPR image was considered the reference standard. Volume-rendered image
      conspicuity was judged for combinations of 7 different postprocessing display
      parameters and compared with MPR images. RESULTS: Definite visualization of the
      embedded objects occurred in 92% of MPR and 13% of VR test situations (P <
      .0001). Volume-rendered display was associated with a mean conspicuity
      degradation of 2.6 on a scale of 0 through 4 (P < .0001) compared with MPR
      methods. The proportion of satisfactory VR images was greatest in test situations
      with a large degree of difference of echogenicity between the background medium
      and the embedded object. The transparent-type postprocessing rendering modes were
      superior to the surface-type rendering modes (P < .0001). CONCLUSIONS: Current 3
      dimensional ultrasonographic MPR imaging display in a solid organ environment
      provides better visualization performance of target and needle conspicuity than
      VR image display when there are not large differences in the signal levels of
      targeted structures and devices compared with surrounding tissues. The difficulty
      in viewing both target and device with VR imaging may restrict its ability to
      guide interventional procedures in some clinical situations.

PMID- 15498912
TI  - Right-to-left shunt assessed by contrast transcranial Doppler sonography: new
      insights.
AB  - OBJECTIVE: Simple diagnostic techniques such as contrast transcranial Doppler
      sonography (cTCDS) are popular for assessing a right-to-left shunt (RLS) because
      of their high sensitivity. In this study, we applied cTCDS to a large patient
      group with a patent foramen ovale, proved by contrast transesophageal
      echocardiography (TEE). METHODS: One hundred one patients with stroke, in whom a
      patent RLS had been shown on contrast TEE, were investigated by TCDS of both
      middle cerebral arteries. Injection of 10 mL of agitated saline was applied
      without and subsequently with the Valsalva maneuver (VM) at the beginning of the
      contrast agent injection, and then 10 mL of a galactose-based contrast agent was
      applied in the same protocol. RESULTS: In all patients, cTCDS with the galactose
      contrast agent showed an RLS when performed with VM, but it showed an RLS in only
      59 patients without VM. In contrast, saline showed an RLS in 54 patients with VM
      and in 20 patients without VM. The differences in diagnostic sensitivity were
      statistically significant (P < .001). Eighteen patients had only 1 microembolic
      signal (MES) after galactose injection, whereas others had more. The mean (SD)
      arrival times of the MES were 9 (6) seconds (range, 1-51 seconds) after galactose
      injection with VM and 9 (3) seconds (range, 2-20 seconds) after agitated saline
      with VM. The differences were not significant. CONCLUSIONS: Contrast TCDS with VM
      shows a TEE-proven RLS with 100% sensitivity, but this was not true with
      galactose application without VM or agitated saline with or without VM.
      Therefore, use of the galactose contrast agent with VM is strongly recommended
      for detecting an RLS on TCDS. However, the arrival time and number of MESs
      detected need to be tested further.

PMID- 15498913
TI  - Color Doppler analysis of vertebral arteries: correlative study with angiographic
      data.
AB  - OBJECTIVE: Color Doppler ultrasonography is the most widespread diagnostic
      procedure in obstructive disease of the arteries supplying the brain. To our
      knowledge, there are only a few correlative color Doppler ultrasonographic and
      angiographic studies of the vertebral arteries, especially in patients who have
      flow-restrictive stenosis at the carotid bifurcation. The main purpose of this
      prospective study was to evaluate diameter, flow volume, and time-averaged mean
      velocities of angiographically verified normal vertebral arteries without
      collateral flow. The second purpose was to try to establish a threshold value for
      the flow volume of the vertebral artery. METHODS: One hundred twenty patients
      referred for carotid angiography with a normal vertebrobasilar system and with no
      patent posterior communicating arteries were investigated with color Doppler
      ultrasonography. Luminal diameter, time-averaged mean velocity, peak systolic
      velocity, and flow volume values were calculated for each patient. The parameters
      were compared between sexes, in different age groups, in patients with carotid
      stenosis of 50% or less and greater than 50%, and in patients who had clinical
      signs of vertebrobasilar insufficiency versus those who had not. RESULTS: We have
      found no significant difference in evaluated parameters with the degree of
      associated carotid stenosis or vertebrobasilar insufficiency. Diameter and flow
      volume values on the left side were higher than on the right side. CONCLUSIONS:
      We found similar flow volume values of vertebral arteries in both sexes and both
      groups of patients with carotid stenosis of 50% or less and greater than 50%. All
      parameters did not differ in patients with stenosis of 50% or less and greater
      than 50% and in patients with and without clinical signs of vertebrobasilar
      insufficiency.

PMID- 15498914
TI  - The role of color duplex sonography in the diagnosis of giant cell arteritis.
AB  - OBJECTIVE: To determine the clinical usefulness of color duplex sonography in the
      diagnosis of giant cell arteritis as an alternative to temporal artery biopsy.
      METHODS: From May 1998 to November 2002, 68 consecutive patients seen in our
      hospital with a clinical suggestion of active temporal arteritis were included.
      Forty-eight patients were female and 20 were male, with a mean age of 77 years.
      Color duplex sonography with a linear array transducer (5-10 MHz) was used to
      assess temporal artery morphologic characteristics before a biopsy was performed.
      The main sonographic criterion for a positive diagnosis was visualization of a
      hypoechoic halo around the temporal artery. These data were compared with
      pathologic findings. The kappa statistic was used to determine the level of
      agreement. Sensitivity, specificity, positive and negative predictive values, and
      accuracy of duplex sonography as a diagnostic test were assessed. RESULTS: The
      color duplex sonographic findings were positive in 25 of 68 patients with a
      clinical suggestion of giant cell arteritis. The diagnosis was confirmed by
      biopsy in 22 patients; there were 4 false-positive results and 1 false-negative
      result by duplex sonography. The kappa value was 0.84. Sensitivity, specificity,
      positive and negative predictive values, and accuracy for duplex sonography were
      95.4%, 91.3%, 84%, 97.6%, and 92.6%, respectively. CONCLUSIONS: The use of high
      resolution color duplex sonography may replace biopsy in the diagnosis of giant
      cell arteritis.

PMID- 15498915
TI  - Sonographic depiction of microvessel perfusion: principles and potential.
AB  - OBJECTIVE: To provide an overview of the technical aspects and potential clinical
      applications of microvessel perfusion as depicted by microbubble-enhanced
      sonography. METHODS: Sonographic depiction of microvessel perfusion was obtained
      by microbubble-enhanced sonography. This technique was used for imaging in vivo
      murine tumors and was correlated with magnetic resonance and fluorodeoxyglucose
      autoradiography. Sonographic estimation of microvessel perfusion used parameters
      derived from time-activity curves. RESULTS: Preliminary data indicate that
      accurate and reproducible quantification of microvessel perfusion is possible
      with the use of microbubble-enhanced sonography. CONCLUSIONS: Microbubble
      enhanced sonography can depict microvessel perfusion. This technique has several
      potential clinical applications, including assessment of tumor blood flow and
      changes that occur with treatment.

PMID- 15498916
TI  - Sonographic features of mesenteric gas.
AB  - OBJECTIVE: To describe the sonographic appearance of air in the mesentery of the
      small bowel. METHODS: Sonography was performed with convex and linear array
      transducers in 2 patients with acute abdomen. RESULTS: In 1 patient, sonography
      revealed fluid and air in the peritoneal cavity. A thick-walled small-bowel loop
      with a thick echogenic mesentery was seen. Air was seen in the mesentery as
      linear bright echoes with acoustic shadowing. An uncomplicated diverticulum was
      seen. In the second patient, air was seen in the thick and echogenic mesentery of
      a thick-walled small bowel. An inflamed diverticulum was also seen. CONCLUSIONS:
      Sonographic features of mesenteric air due to perforated diverticulitis of the
      jejunum are described.

PMID- 15498917
TI  - Syndromes with focal femoral deficiency: strengths and weaknesses of prenatal
      sonography.
AB  - OBJECTIVE: To further characterize the prenatal diagnosis of proximal focal
      femoral deficiency and to contrast this entity with a variety of other
      "syndromes" in which the femur may be deficient. METHODS: We report 2 cases of
      proximal focal femoral deficiency and a case of femoral-facial syndrome. RESULTS:
      A series of 3 women whose fetuses had deficiency of 1 or both femurs were
      carefully analyzed for severity and for similarities and differences with other
      syndromes in which the femur may be deficient, as well as syndromes showing
      global skeletal abnormalities. CONCLUSIONS: Prenatal sonography is a valuable
      tool both for detecting cases of proximal focal femoral deficiency, separating
      them from syndromes showing global skeletal abnormalities, and for stratifying
      them according to severity.

PMID- 15498918
TI  - Three-dimensional power Doppler angiographic features of placental chorioangioma.

PMID- 15498919
TI  - Abnormal placental structure and vasa previa: confirmation of the relationship.

PMID- 15498920
TI  - Unresorbed corpora albicantia mimicking a sonographically solid ovarian mass in a
      postmenopausal woman.

PMID- 15498921
TI  - Gastric schwannoma: sonographic findings.

PMID- 15498922
TI  - Lower extremity arterial air embolism secondary to clostridial gas gangrene:
      diagnosis by Doppler sonography.

PMID- 15498923
TI  - Subcellular localization as a limiting factor for utilization of decoy
      oligonucleotides.
AB  - Transfection of cells with short double-stranded synthetic DNA molecules that
      contain a transcription factor binding site, known as decoy oligodeoxynucleotides
      (ODNs), has been proposed as a novel approach in vitro and in vivo for the study
      of gene regulation and for gene therapy. Once delivered into cells, decoy ODNs
      are predicted to bind to nuclear transcription factors, preventing their binding
      to consensus sequences in target genes. Using a fluorescein-labeled decoy ODN
      containing a consensus sequence for the AP-1 transcription factor, we show that
      lipid-complexed decoys were readily transfectable into cells, but were
      consistently detectable in the cytoplasm and not in the nucleus. The same
      phenomenon was observed in three different cell lines including KB-3, CHO and MDA
      MB-231. The AP-1 decoy ODNs failed to inhibit the transcriptional activity of an
      AP-1-dependent luciferase reporter. The effect of cytoplasmic AP-1 decoy ODNs on
      the subcellular localization and function of c-Jun induced by the microtubule
      inhibitor vinblastine, which strongly induced c-Jun expression, was assessed. No
      difference in protein level or nuclear localization of vinblastine-induced c-Jun,
      or of one of its target genes, p53, was noted when cells were transfected with
      wild-type or mutated forms of the decoy ODNs. We suggest that subcellular
      localization is an unappreciated and key limiting factor for the use of
      transcription factor decoy ODNs that must be addressed before meaningful data
      interpretation can be made.

PMID- 15498924
TI  - A novel method of identifying genetic mutations using an electrochemical DNA
      array.
AB  - We describe the development of a new type of DNA array chip that utilizes
      electrochemical reactions and a novel method of simultaneously identifying
      multiple genetic mutations on an array chip. The electrochemical array (ECA) uses
      a threading intercalator specific to double-stranded nucleotides,
      ferrocenylnaphthalene diimide (FND), as the indicator. ECA does not require
      target labeling, and the equipment is simple, durable and less expensive. The
      simultaneous multiple mutation detection (SMMD) system using an ECA chip and FND
      utilizes an enzyme to simultaneously distinguish several genetic mutations such
      as single nucleotide polymorphism (SNP), insertion, deletion, translocation and
      short tandem repeat. We examined this SMMD system using an ECA chip, by detecting
      seven different mutations on the lipoprotein lipase (LPL) gene for 50 patients in
      a blind test. It turned out that all the results obtained were concordant with
      the sequencing results, demonstrating that this system is a powerful tool for
      clinical applications.

PMID- 15498925
TI  - Enhancement of camptothecin-induced topoisomerase I cleavage complexes by the
      acetaldehyde adduct N2-ethyl-2'-deoxyguanosine.
AB  - The activity of DNA topoisomerase I (Top1), an enzyme that regulates DNA
      topology, is impacted by DNA structure alterations and by the anticancer alkaloid
      camptothecin (CPT). Here, we evaluated the effect of the acetaldehyde-derived DNA
      adduct, N2-ethyl-2'-deoxyguanosine (N2-ethyl-dG), on human Top1 nicking and
      closing activities. Using purified recombinant Top1, we show that Top1 nicking
      closing activity remains unaffected in N2-ethyl-dG adducted oligonucleotides.
      However, the N2-ethyl-dG adduct enhanced CPT-induced Top1-DNA cleavage complexes
      depending on the relative position of the N2-ethyl-dG adduct with respect to the
      Top1 cleavage site. The Top1-mediated DNA religation (closing) was selectively
      inhibited when the N2-ethyl-dG adduct was present immediately 3' from the Top1
      site (position +1). In addition, when the N2-ethyl-dG adduct was located at the 
      5 position, CPT enhanced cleavage at an alternate Top1 cleavage site immediately
      adjacent to the adduct, which was then at position +1 relative to this new
      alternate Top1 site. Modeling studies suggest that the ethyl group on the N2
      ethyl-dG adduct located at the 5' end of a Top1 site (position +1) sterically
      blocks the dissociation of CPT from the Top1-DNA complex, thereby inhibiting
      further the religation (closing) reaction.

PMID- 15498927
TI  - EphA2 induction of fibronectin creates a permissive microenvironment for
      malignant cells.
AB  - Normal and metastatic cells continuously exchange information with the
      surrounding tissue environment, and this communication governs many aspects of
      cell behavior. In particular, the physical placement or adhesions of cells within
      their environment are increasingly understood to facilitate this communication.
      Classically, cell-cell and cell-extracellular matrix adhesions have been viewed
      as separable events that are independently controlled. This simple view is
      changing, as evidence emerges of coordinated regulation of cellular adhesions.
      Here, we show that the EphA2 tyrosine kinase, which is overexpressed in many
      aggressive cancers, regulates a fine balance of cell-cell and cell-extracellular
      matrix adhesions in epithelial cells. EphA2 selectively inhibits cell-cell
      adhesions by increasing cell attachment and up-regulating the extracellular
      matrix protein fibronectin. We also show that fibronectin can contribute to
      important aspects of malignant character. Antibody-based targeting of EphA2
      inhibits malignant cell growth by decreasing fibronectin and thereby inducing
      apoptotic death. Our findings strengthen a concept that cancer progression is
      regulated by a bidirectional communication between tumor cells and their
      surrounding microenvironment.

PMID- 15498926
TI  - Expression profiles frame the promoter specificity dilemma of the ETS family of
      transcription factors.
AB  - Sequence-specific DNA binding proteins that function as transcription factors are
      frequently encoded by gene families. Such proteins display highly conserved DNA
      binding properties, yet are expected to retain promoter selectivity. In this
      report we investigate this problem using the ets gene family, a group of metazoan
      genes whose members regulate cell growth and differentiation and are mutated in
      human cancers. We tested whether the level of mRNA can serve as a specificity
      determinant. The mRNA levels of the 27 paralogous human ets genes were measured
      in 23 tissues and cell lines. Real-time RT-PCR provided accurate measurement of
      absolute mRNA levels for each gene down to one copy per cell. Surprisingly, at
      least 16 paralogs were expressed in each cell sample and over half were expressed
      ubiquitously. Tissues and complementary cell lines showed similar expression
      patterns, indicating that tissue complexity was not a limitation. There was no
      unique, highly expressed gene for each cell type. Instead, one of only eight ets
      genes showed the highest expression in all samples. DNA binding studies
      illustrate both overlapping and unique specificities for ubiquitous ETS proteins.
      These findings establish the parameters of the promoter specificity dilemma
      within the ets family of transcription factors.

PMID- 15498928
TI  - Peroxisome proliferator-activated receptor gamma ligands improve the antitumor
      efficacy of thrombospondin peptide ABT510.
AB  - An expanding capillary network is critical for several pathologic conditions. In
      cancer, the decrease of antiangiogenic thrombospondin-1 (TSP1) often enables an
      angiogenic switch, which can be reversed with exogenous TSP1 or its peptide
      derivative ABT510. TSP1 acts by inducing endothelial cell apoptosis via signaling
      cascade initiated at CD36, a TSP1 antiangiogenic receptor. Here, we show that the
      ligands of nuclear receptor peroxisome proliferator-activated receptor gamma
      (PPARgamma), 15-deoxy-delta(12,14)-prostaglandin J2, troglitazone, and
      rosiglitazone increased PPARgamma and CD36 expression in endothelial cells and
      improved the efficacy of TSP1 and ABT510 in a CD36-dependent manner. The ABT510
      and PPARgamma ligands cooperatively blocked angiogenic endothelial functions in
      vitro and neovascularization in vivo. In tumor xenografts, 15-deoxy-delta(12,14)
      prostaglandin J2 and troglitazone synergistically improved antiangiogenic and
      antitumor effects of ABT510. Our data provide one mechanism for the in vivo
      angioinhibitory effect of PPARgamma ligands and show fine-tuning of the
      antiangiogenic efficacy via targeted up-regulation of the endothelial receptor.

PMID- 15498929
TI  - Bcl-2-mediated cell survival promotes metastasis of EpH4 betaMEKDD mammary
      epithelial cells.
AB  - The majority of patients who succumb to cancer die from metastatic disease
      progression rather than from the primary tumor. Elucidation of the mechanisms
      underlying tissue-specific metastasis is essential to the development of
      effective therapies. The mitogen-activated protein kinase kinase (MEK) pathway is
      frequently activated in human tumors and has been shown to regulate genes
      involved in proliferation, migration, and invasion. Studies with MEK-transformed
      EpH4 mouse mammary epithelial cells showed that these cells are highly
      tumorigenic but have a limited metastatic ability. Detachment of epithelial cells
      from the extracellular matrix causes disruption of the actin cytoskeleton and
      induces apoptosis. Several metastatic breast carcinoma cell lines have been shown
      to be resistant to cell death following actin disruption. This death-resistant
      phenotype can be modeled by overexpressing the antiapoptotic Bcl-2 protein in
      cells. This suggests that mechanisms that regulate survival of extravasated tumor
      cells may enhance metastatic efficiency. Therefore, we examined whether
      expression of Bcl-2 in MEK-transformed EpH4 mammary epithelial cells could
      provide a survival advantage and promote metastasis. Expression of Bcl-2 in
      parental EpH4 mammary epithelial cells or MEK-transformed cells was insufficient
      to induce increased migration, invasion, or tumor development. However, Bcl-2
      expression markedly enhanced spontaneous lung metastasis from orthotopically
      implanted primary tumors. These results clearly show that mechanisms that
      regulate primary tumor development are distinct from those that promote
      metastasis and that assays designed to isolate genes involved in transformation
      may fail to identify genes that are critical regulators of metastasis.

PMID- 15498930
TI  - Low-dose radiation hypersensitivity is associated with p53-dependent apoptosis.
AB  - Exposure to environmental radiation and the application of new clinical
      modalities, such as radioimmunotherapy, have heightened the need to understand
      cellular responses to low dose and low-dose rate ionizing radiation. Many tumor
      cell lines have been observed to exhibit a hypersensitivity to radiation doses
      <50 cGy, which manifests as a significant deviation from the clonogenic survival
      response predicted by a linear-quadratic fit to higher doses. However, the
      underlying processes for this phenomenon remain unclear. Using a gel
      microdrop/flow cytometry assay to monitor single cell proliferation at early
      times postirradiation, we examined the response of human A549 lung carcinoma,
      T98G glioma, and MCF7 breast carcinoma cell lines exposed to gamma radiation
      doses from 0 to 200 cGy delivered at 0.18 and 22 cGy/min. The A549 and T98G
      cells, but not MCF7 cells, showed the marked hypersensitivity at doses <50 cGy.
      To further characterize the low-dose hypersensitivity, we examined the influence
      of low-dose radiation on cell cycle status and apoptosis by assays for active
      caspase-3 and phosphatidylserine translocation (Annexin V binding). We observed
      that caspase-3 activation and Annexin V binding mirrored the proliferation curves
      for the cell lines. Furthermore, the low-dose hypersensitivity and Annexin V
      binding to irradiated A549 and T98G cells were eliminated by treating the cells
      with pifithrin, an inhibitor of p53. When p53-inactive cell lines (2800T skin
      fibroblasts and HCT116 colorectal carcinoma cells) were examined for similar
      patterns, we found that there was no hyperradiosensitivity and apoptosis was not
      detectable by Annexin V or caspase-3 assays. Our data therefore suggest that low
      dose hypersensitivity is associated with p53-dependent apoptosis.

PMID- 15498931
TI  - In vivo recombination after chronic damage exposure falls to below spontaneous
      levels in "recombomice".
AB  - All forms of cancer are initiated by heritable changes in gene expression.
      Although point mutations have been studied extensively, much less is known about
      homologous recombination events, despite its role in causing sequence
      rearrangements that contribute to tumorigenesis. Although transgenic mice that
      permit detection of point mutations have provided a fundamental tool for studying
      point mutations in vivo, until recently, transgenic mice designed specifically to
      detect homologous recombination events in somatic tissues in vivo did not exist.
      We therefore created fluorescent yellow direct repeat mice, enabling automated
      detection of recombinant cells in vivo for the first time. Here, we show that an
      acute dose of ionizing radiation induces recombination in fluorescent yellow
      direct repeat mice, providing some of the first direct evidence that ionizing
      radiation induces homologous recombination in cutaneous tissues in vivo. In
      contrast, the same total dose of radiation given under chronic exposure
      conditions suppresses recombination to levels that are significantly below those
      of unexposed animals. In addition, global methylation is suppressed and key DNA
      repair proteins are induced in tissues from chronically irradiated animals
      (specifically AP endonuclease, polymerase beta, and Ku70). Thus, increased
      clearance of recombinogenic lesions may contribute to suppression of homologous
      recombination. Taken together, these studies show that fluorescent yellow direct
      repeat mice provide a rapid and powerful assay for studying the recombinogenic
      effects of both short-term and long-term exposure to DNA damage in vivo and
      reveal for the first time that exposure to ionizing radiation can have opposite
      effects on genomic stability depending on the duration of exposure.

PMID- 15498932
TI  - Tumor necrosis factor-related apoptosis-inducing ligand-mediated activation of
      mitochondria-associated nuclear factor-kappaB in prostatic carcinoma cell lines.
AB  - It has been suggested that some nuclear transcription factors may participate in
      the regulation of mitochondrial functions through transcriptional control of
      mitochondrial DNA. Very little is known about the response of transcription
      factors within mitochondria to the activation of death receptors. Recent
      publications indicate that nuclear factor-kappaB (NF-kappaB) is localized in
      mitochondria of mammalian cells. Because of the critical role of mitochondria in
      the execution of many apoptotic pathways, we suggest that NF-kappaB-dependent
      mechanisms operating at the level of mitochondria contribute to its role in
      regulating death receptor signaling. We have found NF-kappaB p65 and p50 subunits
      with DNA binding activity in the mitochondria of prostatic carcinoma cell lines.
      Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) affects DNA
      binding activity of mitochondria-associated NF-kappaB but does not change the
      amount of p65 in mitochondria, which suggests activation of mitochondrial NF
      kappaB without additional translocation of NF-kappaB subunits to mitochondria. We
      have also shown that TRAIL decreases mitochondrial genome encoded mRNA levels and
      inhibition of NF-kappaB prevents this decrease. TRAIL effects on mitochondrial NF
      kappaB-DNA binding and mitochondrial genome encoded mRNA levels also depend on
      Bcl-2 overexpression. In addition, transcription factor activator protein-1 with
      DNA binding activity is also found in mitochondria of prostatic carcinoma cells
      and TRAIL treatment affects this binding. In summary, NF-kappaB is found in
      mitochondria of prostatic carcinoma cells, where it is thought to regulate
      mitochondria genome encoded mRNA levels in response to TRAIL treatment.

PMID- 15498933
TI  - Development of head and neck squamous cell carcinoma is associated with altered
      cytokine responsiveness.
AB  - Growth of head and neck squamous cell carcinoma (HNSCC) is generally associated
      with an inflammatory component. It is hypothesized that these tumor cells develop
      mechanisms to evade the growth inhibitory effects of cytokines that are present
      in the tumor microenvironment. This study determined the changes in
      responsiveness to inflammatory cytokines that accompany the transition of normal
      to transformed epithelial cells. Paired primary cultures of normal epithelial
      cells (NEC) and SCC cells were established from 16 patients. Receptor-mediated
      activation of signal transducer and activator of transcription and extracellular
      signal-regulated kinase pathways in response to cytokine treatments was
      identified by immunoblot analysis. Thymidine incorporation determined the impact
      of the cytokines on DNA synthesis. HNNEC and HNSCC displayed a prominent
      signaling in response to oncostatin M, interleukin-6, IFN-gamma, and epidermal
      growth factor. Untreated HNSCC showed an elevated level of phosphorylated signal
      transducer and activator of transcription 3 and extracellular signal-regulated
      kinase (P < 0.001) compared with HNNEC, suggesting constitutively activated
      pathways. Moreover, HNSCC cells phosphorylated significantly more signal
      transducer and activator of transcription 1 in response to oncostatin M (P =
      0.002) and IFN-gamma (P = 0.018) treatments. DNA synthesis of SCC cells was less
      inhibited by cytokines produced by endotoxin-stimulated macrophages (P = 0.016)
      than that of NEC. Low-dose oncostatin M slightly enhanced proliferation of SCC,
      whereas that of NEC was suppressed (P = 0.016). This study identified significant
      alterations in signal transduction pathways engaged by cytokines and which are
      associated with loss of growth inhibition of HNSCC. Increased signal transducer
      and activator of transcription phosphorylation, along with constitutively
      phosphorylated extracellular signal-regulated kinase in HNSCC, suggest that these
      pathways as molecular markers are important in the malignant transformation
      process and are potential targets for treatment.

PMID- 15498934
TI  - Predicting enzyme family class in a hybridization space.
AB  - Given the sequence of a protein, how can we predict whether it is an enzyme or a
      non-enzyme? If it is, what enzyme family class it belongs to? Because these
      questions are closely relevant to the biological function of a protein and its
      acting object, their importance is self-evident. Particularly with the explosion
      of protein sequences entering into data banks and the relatively much slower
      progress in using biochemical experiments to determine their functions, it is
      highly desired to develop an automated method that can be used to give fast
      answers to these questions. By hybridizing the gene ontology and pseudo-amino
      acid composition, we have introduced a new method that is called GO-PseAA
      predictor and operate it in a hybridization space. To avoid redundancy and bias,
      demonstrations were performed on a data set in which none of the proteins in an
      individual class has > or =40% sequence identity to any other. The overall
      success rate thus obtained by the jackknife cross-validation test in identifying
      enzyme and non-enzyme was 93%, and that in identifying the enzyme family was 94%
      for the following six main Enzyme Commission (EC) classes: (1) oxidoreductase,
      (2) transferase, (3) hydrolase, (4) lyase, (5) isomerase, and (6) ligase. The
      corresponding rates by the independent data set test were 98% and 97%,
      respectively.

PMID- 15498935
TI  - Folding of a designed simple ankyrin repeat protein.
AB  - Ankyrin repeats (AR) are 33-residue motifs containing a beta-turn, followed by
      two alpha-helices connected by a loop. AR occur in tandem arrangements and stack
      side-by-side to form elongated domains involved in very different cellular tasks.
      Recently, consensus libraries of AR repeats were constructed. Protein E1_5
      represents a member of the shortest library, and consists of only a single
      consensus repeat flanked by designed N- and C-terminal capping repeats. Here we
      present a biophysical characterization of this AR domain. The protein is
      compactly folded, as judged from the heat capacity of the native state and from
      the specific unfolding enthalpy and entropy. From spectroscopic data, thermal and
      urea-induced unfolding can be modeled by a two-state transition. However,
      scanning calorimetry experiments reveal a deviation from the two-state behavior
      at elevated temperatures. Folding and unfolding at 5 degrees C both follow
      monoexponential kinetics with k(folding) = 28 sec(-1) and k(unfolding) = 0.9 sec(
      1). Kinetic and equilibrium unfolding parameters at 5 degrees C agree very well.
      We conclude that E1_5 folds in a simple two-state manner at low temperatures
      while equilibrium intermediates become populated at higher temperatures. A
      chevron-plot analysis indicates that the protein traverses a very compact
      transition state along the folding/unfolding pathway. This work demonstrates that
      a designed minimal ankyrin repeat protein has the thermodynamic and kinetic
      properties of a compactly folded protein, and explains the favorable properties
      of the consensus framework.

PMID- 15498936
TI  - To be folded or to be unfolded?
AB  - The lack of ordered structure in "natively unfolded" proteins raises a general
      question: Are there intrinsic properties of amino acid residues that are
      responsible for the absence of fixed structure at physiological conditions? In
      this article, we demonstrate that the competence of a protein to be folded or to
      be unfolded may be determined by the property of amino acid residues to form a
      sufficient number of contacts in a globular state. The expected average number of
      contacts per residue calculated from the amino acid sequence alone (using the
      average number of contacts for 20 amino acid residues in globular proteins) can
      be used as one of the simple indicators of natively unfolded proteins. The
      prediction accuracy for the sets of 80 folded and 90 natively unfolded proteins
      reaches 89% if the expected average number of contacts is used as a parameter and
      83% in the case of hydrophobicity. An optimal set of artificial parameters for 20
      amino acid residues obtained by Monte Carlo algorithm to maximally separate the
      sets of 90 natively unfolded and 80 folded proteins demonstrates the upper limit
      for prediction accuracy, which is 95%.

PMID- 15498937
TI  - Solvent effects on the conformational transition of a model polyalanine peptide.
AB  - We have investigated the folding of polyalanine by combining discontinuous
      molecular dynamics simulation with our newly developed off-lattice intermediate
      resolution protein model. The thermodynamics of a system containing a single Ac
      KA(14)K-NH(2) molecule has been explored by using the replica exchange simulation
      method to map out the conformational transitions as a function of temperature. We
      have also explored the influence of solvent type on the folding process by
      varying the relative strength of the side-chain's hydrophobic interactions and
      backbone hydrogen bonding interactions. The peptide in our simulations tends to
      mimic real polyalanine in that it can exist in three distinct structural states:
      alpha-helix, beta-structures (including beta-hairpin and beta-sheet-like
      structures), and random coil, depending upon the solvent conditions. At low
      values of the hydrophobic interaction strength between nonpolar side-chains, the
      polyalanine peptide undergoes a relatively sharp transition between an alpha
      helical conformation at low temperatures and a random-coil conformation at high
      temperatures. As the hydrophobic interaction strength increases, this transition
      shifts to higher temperatures. Increasing the hydrophobic interaction strength
      even further induces a second transition to a beta-hairpin, resulting in an alpha
      helical conformation at low temperatures, a beta-hairpin at intermediate
      temperatures, and a random coil at high temperatures. At very high values of the
      hydrophobic interaction strength, polyalanines become beta-hairpins and beta
      sheet-like structures at low temperatures and random coils at high temperatures.
      This study of the folding of a single polyalanine-based peptide sets the stage
      for a study of polyalanine aggregation in a forthcoming paper.

PMID- 15498938
TI  - NMR and molecular dynamics studies of the interaction of melatonin with
      calmodulin.
AB  - Pineal hormone melatonin (N-acetyl-5-methoxytryptamine) is thought to modulate
      the calcium/calmodulin signaling pathway either by changing intracellular Ca(2+)
      concentration via activation of its G-protein-coupled membrane receptors, or
      through a direct interaction with calmodulin (CaM). The present work studies the
      direct interaction of melatonin with intact calcium-saturated CaM both
      experimentally, by fluorescence and nuclear magnetic resonance spectroscopies,
      and theoretically, by molecular dynamics simulations. The analysis of the
      experimental data shows that the interaction is calcium-dependent. The affinity,
      as obtained from monitoring (15)N and (1)H chemical shift changes for a melatonin
      titration, is weak (in the millimolar range) and comparable for the N- and C
      terminal domains. Partial replacement of diamagnetic Ca(2+) by paramagnetic
      Tb(3+) allowed the measurement of interdomain NMR pseudocontact shifts and
      residual dipolar couplings, indicating that each domain movement in the complex
      is not correlated with the other one. Molecular dynamics simulations allow us to
      follow the dynamics of melatonin in the binding pocket of CaM. Overall, this
      study provides an example of how a combination of experimental and theoretical
      approaches can shed light on a weakly interacting system of biological and
      pharmacological significance.

PMID- 15498939
TI  - Position dependence of the 13C chemical shifts of alpha-helical model peptides.
      Fingerprint of the 20 naturally occurring amino acids.
AB  - The position dependence of the (13)C chemical shifts was investigated at the
      density functional level for alpha-helical model peptides represented by the
      sequence Ac-(Ala)(i)-X-(Ala)(j)-NH(2), where X represents any of the 20 naturally
      occurring amino acids, with 0 < or = i < or = 8 and i + j = 8. Adoption of the
      locally dense basis approach for the quantum chemical calculations enabled us to
      reduce the length of the chemical-shift calculations while maintaining good
      accuracy of the results. For the 20 naturally occurring amino acids in alpha
      helices, there is (1) significant variability of the computed (13)C shielding as
      a function of both the guest residue (X) and the position along the sequence; for
      example, at the N terminus, the (13)C(alpha) and (13)C(beta) shieldings exhibit a
      uniform pattern of variation with respect to both the central or the C-terminal
      positions; (2) good agreement between computed and observed (13)C(alpha) and
      (13)C(beta) chemical shifts in the interior of the helix, with correlation
      coefficients of 0.98 and 0.99, respectively; for (13)C(alpha) chemical shifts,
      computed in the middle of the helix, only five residues, namely Asn, Asp, Ser,
      Thr, and Leu, exhibit chemical shifts beyond the observed standard deviation; and
      (3) better agreement for four of these residues (Asn, Asp, Ser, and Thr) only for
      the computed values of the (13)C(alpha) chemical shifts at the N terminus. The
      results indicate that (13)C(beta), but not (13)C(beta), chemical shifts are
      sensitive enough to reflect the propensities of some amino acids for specific
      positions within an alpha-helix, relative to the N and C termini of peptides and
      proteins.

PMID- 15498940
TI  - Molecular dynamics simulation of the interaction between the complex iron-sulfur
      flavoprotein glutamate synthase and its substrates.
AB  - Glutamate synthase (GltS) is a complex iron-sulfur flavoprotein that catalyzes
      the reductive transfer of L-glutamine amide group to the C2 carbon of 2
      oxoglutarate yielding two molecules of L-glutamate. Molecular dynamics
      calculations in explicit solvent were carried out to gain insight into the
      conformational flexibility of GltS and into the role played by the enzyme
      substrates in regulating the catalytic cycle. We have modelled the free
      (unliganded) form of Azospirillum brasilense GltS alpha subunit and the structure
      of the reduced enzyme in complex with the L-glutamine and 2-oxoglutarate
      substrates starting from the crystallographically determined coordinates of the
      GltS alpha subunit in complex with L-methionine sulphone and 2-oxoglutarate. The
      present 4-ns molecular dynamics calculations reveal that the GltS glutaminase
      site may exist in a catalytically inactive conformation unable to bind glutamine,
      and in a catalytically competent conformation, which is stabilized by the
      glutamine substrate. Substrates binding also induce (1) closure of the loop
      formed by residues 263-271 with partial shielding of the glutaminase site from
      solvent, and (2) widening of the ammonia tunnel entrance at the glutaminase end
      to allow for ammonia diffusion toward the synthase site. The Q-loop of glutamate
      synthase, which acts as an active site lid in other amidotransferases, seems to
      maintain an open conformation. Finally, binding of L-methionine sulfone, a
      glutamine analog that mimics the tetrahedral transient species occurring during
      its hydrolysis, causes a coordinated rigid-body motion of segments of the
      glutaminase domain that results in the inactive conformation observed in the
      crystal structure of GltS alpha subunit.

PMID- 15498941
TI  - Evolutionarily conserved regions and hydrophobic contacts at the superfamily
      level: The case of the fold-type I, pyridoxal-5'-phosphate-dependent enzymes.
AB  - The wealth of biological information provided by structural and genomic projects
      opens new prospects of understanding life and evolution at the molecular level.
      In this work, it is shown how computational approaches can be exploited to
      pinpoint protein structural features that remain invariant upon long evolutionary
      periods in the fold-type I, PLP-dependent enzymes. A nonredundant set of 23
      superposed crystallographic structures belonging to this superfamily was built.
      Members of this family typically display high-structural conservation despite low
      sequence identity. For each structure, a multiple-sequence alignment of
      orthologous sequences was obtained, and the 23 alignments were merged using the
      structural information to obtain a comprehensive multiple alignment of 921
      sequences of fold-type I enzymes. The structurally conserved regions (SCRs), the
      evolutionarily conserved residues, and the conserved hydrophobic contacts (CHCs)
      were extracted from this data set, using both sequence and structural
      information. The results of this study identified a structural pattern of
      hydrophobic contacts shared by all of the superfamily members of fold-type I
      enzymes and involved in native interactions. This profile highlights the presence
      of a nucleus for this fold, in which residues participating in the most conserved
      native interactions exhibit preferential evolutionary conservation, that
      correlates significantly (r = 0.70) with the extent of mean hydrophobic contact
      value of their apolar fraction.

PMID- 15498942
TI  - Distinct protein interfaces in transmembrane domains suggest an in vivo folding
      model.
AB  - Given the known high-resolution structures of alpha-helical transmembrane
      domains, we show that there are statistically distinct classes of transmembrane
      interfaces which relate to the folding and oligomerization of transmembrane
      domains. Distinct types of interfaces have been categorized and refer to those
      between: the same polypeptide chain, different polypeptide chains, helices that
      are sequential neighbors, and those that are nonsequential. These different
      interfaces may reflect different phases in the mechanism of transmembrane domain
      folding and are consistent with the current experimental evidence pertaining to
      the folding and oligomerization of transmembrane domains. The classes of helix
      helix interfaces have been identified in terms of the numbers and different types
      of pairwise amino acid interactions. The specific measures used are interaction
      entropy, the information content of interacting partners compared to a random set
      of contacts, the amino acid composition of the classes and the abundances of
      specific amino acid pairs in close contact. Knowledge of the clear differences in
      the types of helix-helix contacts helps with the derivation of knowledge-based
      constraints which until now have focused on only the interiors of transmembrane
      domains as compared to the exterior. Taken together, an in vivo model for
      membrane protein folding is presented, which is distinct from the familiar two
      stage model. The model takes into account the different interfaces of membrane
      helices defined herein, and the available data regarding folding in the
      translocation channel.

PMID- 15498944
TI  - Of torques, forces, and protein machines.

PMID- 15498945
TI  - My life with affinity.

PMID- 15498946
TI  - The birth of transplantation immunology: the Billingham-Medawar experiments at
      Birmingham University and University College London. 1951.

PMID- 15498947
TI  - Tuna comparative physiology.
AB  - Thunniform swimming, the capacity to conserve metabolic heat in red muscle and
      other body regions (regional endothermy), an elevated metabolic rate and other
      physiological rate functions, and a frequency-modulated cardiac output
      distinguish tunas from most other fishes. These specializations support
      continuous, relatively fast swimming by tunas and minimize thermal barriers to
      habitat exploitation, permitting niche expansion into high latitudes and to ocean
      depths heretofore regarded as beyond their range.

PMID- 15498948
TI  - Inflation of the esophagus and vocal tract filtering in ring doves.
AB  - Ring doves vocalize with their beaks and nostrils closed, exhaling into
      inflatable chambers in the head and neck region. The source sound produced at the
      syrinx contains a fundamental frequency with prominent second and third harmonic
      overtones, but these harmonics are filtered out of the emitted signal. We show by
      cineradiography that the upper esophagus, oral and nasal cavities collect the
      expired air during vocalization and that the inflated esophagus becomes part of
      the suprasyringeal vocal tract. The level of the second and third harmonics,
      relative to the fundamental frequency (f(0)), is reduced in the esophagus and
      emitted vocalization compared with in the trachea, although these harmonics are
      still considerably higher in the esophagus than in the emitted signal. When the
      esophagus is prevented from fully inflating, there is a pronounced increase in
      the level of higher harmonics in the emitted vocalization. Our data suggest that
      the trachea and esophagus act in series as acoustically separate compartments
      attenuating harmonics by different mechanisms. We hypothesize that the trachea
      behaves as a tube closed at the syringeal end and with a variable, restricted
      opening at the glottal end that lowers the tracheal first resonance to match the
      f(0) of the coo. The inflated esophagus may function as a Helmholtz resonator in
      which the elastic walls form the vibrating mass. Such a resonator could support
      the f(0) over a range of inflated volumes.

PMID- 15498949
TI  - Kinematics of aquatic and terrestrial escape responses in mudskippers.
AB  - Escape responses in fishes are rapid behaviors that are critical for survival.
      The barred mudskipper (Periophthalmus argentilineatus) is an amphibious fish that
      must avoid predators in two environments. We compared mudskipper terrestrial and
      aquatic escapes to address two questions. First, how does an amphibious fish
      perform an escape response in a terrestrial environment? Second, how similar is a
      terrestrial escape response to an aquatic escape response? Because a mudskipper
      on land does not have to contend with the high viscosity of water, we predicted
      that, if the same behavior is employed across environments, terrestrial escape
      responses should have 'better' performance (higher velocity and more rapid
      completion of movements) when compared with aquatic escape responses. By
      contrast, we predicted that intervertebral bending would be similar across
      environments because previous studies of escape response behaviors in fishes have
      proposed that vertebral morphology constrains intervertebral bending. High-speed
      digital imaging was used to record mudskipper escapes in water and on land, and
      the resulting images were used to calculate intervertebral bending during the
      preparatory phase, peak velocity and acceleration of the center of mass during
      the propulsive phase, and relative timing of movements. Although similar maximum
      velocities are achieved across environments, terrestrial responses are distinct
      from aquatic responses. During terrestrial escapes, mudskippers produce greater
      axial bending in the preparatory phase, but only in the posterior region of the
      body and over a much longer time period. Mudskippers also occasionally produced
      the 'wrong' behavior for a given environment. Thus, it appears that the same
      locomotor morphology is recruited differently by the central nervous system to
      produce a distinct behavior appropriate for each environment.

PMID- 15498950
TI  - Metabolic influences of fiber size in aerobic and anaerobic locomotor muscles of
      the blue crab, Callinectes sapidus.
AB  - Diameters of some white locomotor muscle fibers in the adult blue crab,
      Callinectes sapidus, exceed 500 microm whereas juvenile white fibers are <100
      microm. It was hypothesized that aerobically dependent processes, such as
      metabolic recovery following burst contractions, will be significantly impeded in
      the large white fibers. In addition, dark aerobic fibers of adults, which rely on
      aerobic metabolism for both contraction and recovery, grow as large as the white
      fibers. These large aerobic fibers are subdivided, however, thus decreasing the
      effective diameter of each metabolic functional unit and enabling aerobic
      contraction. The two goals of this study were: (1) to characterize the
      development of subdivisions in the dark levator muscle fibers and (2) to monitor
      post-contractile metabolism as a function of fiber size in aerobic and anaerobic
      levator muscles. Dark levator muscle fibers from crabs ranging from <0.1 g to
      >190 g were examined with transmission electron microscopy to determine the
      density of mitochondria and subdivision diameters. Across all size classes, there
      was a constant mitochondrial fractional area (25% of the total subdivision area)
      and subdivision size (mean diameter of 36.5+/-2.7 microm). Thus, blue crab dark
      levator fibers are unusual in having metabolic functional units (subdivisions)
      that do not increase in size during development while the contractile functional
      units (fibers) grow hypertrophically. The body mass scaling of post-contractile
      lactate dynamics was monitored during recovery from anaerobic, burst exercise in
      white and dark muscle, and in hemolymph. There were no differences among size
      classes in lactate accumulation during exercise in either muscle. However, in
      white fibers from large crabs, lactate continued to increase after exercise, and
      lactate removal from tissues required a much longer period of time relative to
      smaller crabs. Differences in lactate removal among size classes were less
      pronounced in dark fibers, and post-contractile lactate accumulation was
      significantly higher in white than in dark fibers from large animals. These data
      suggest that the large white fibers invoke anaerobic metabolism following
      contraction to accelerate certain phases of metabolic recovery that otherwise
      would be overly slow. This implies that, in addition to the typical mass-specific
      decrease in oxidative capacity that accompanies increases in animal mass, aerobic
      metabolic processes become increasingly limited by surface area to volume and
      intracellular diffusion constraints in developing white muscle fibers.

PMID- 15498951
TI  - Why do macaroni penguins choose shallow body angles that result in longer descent
      and ascent durations?
AB  - It is generally assumed that air-breathing aquatic animals always choose the
      shortest route to minimize duration for transit between the surface and foraging
      depth in order to maximize the proportion of time spent foraging. However,
      empirical data indicate that the body angles of some diving animals are rarely
      vertical during descent and ascent. Why do they choose shallower body angles that
      result in longer descent and ascent durations? To investigate this question, we
      attached acceleration data loggers to eight female macaroni penguins, breeding on
      the Kerguelen Islands (48 degrees 45'-50 degrees 00' S, 68 degrees 45'-70 degrees
      58' E; South Indian Ocean), to record depth, two-dimensional acceleration (stroke
      cycle frequency and body angle) and temperature. We investigated how they
      controlled body angle and allocated their submerged time. The instrumented
      females performed multiple dives (N=6952) with a mean dive depth for each bird
      ranging from 24.5+/-28.5 m to 56.4+/-75.1 m. Mean body angles during descent and
      ascent were not vertical. There was large variation in mean descent and ascent
      angles for a given dive depth, which, in turn, caused large variation in descent
      and ascent duration. Body angles were significantly correlated with time spent at
      the bottom-phase of the dive. Birds that spent long periods at the bottom
      exhibited steep body angles during ascent and subsequent descent. By contrast,
      they adopted shallow body angles after they had short or no bottom phases. Our
      results suggest that macaroni penguins stay at the bottom longer after
      encountering a good prey patch and then travel to the surface at steep body
      angles. If they do not encounter prey, they discontinue the dive, without staying
      at the bottom, ascend at shallow body angles and descend at shallow body angles
      in a subsequent dive. A shallow body angle can increase the horizontal distance
      covered during a dive, contributing to the move into a more profitable area in
      the following dive. During the ascent, in particular, macaroni penguins stopped
      beating their flippers. The buoyantly gliding penguins can move horizontally with
      minimum stroking effort before reaching the surface.

PMID- 15498952
TI  - Developmental plasticity of physiology and morphology in diet-restricted European
      shag nestlings (Phalacrocorax aristotelis).
AB  - Growing animals may exhibit developmental plasticity as an adaptation to
      variability in the environmental conditions during development. We examined
      physiological and morphological responses to short-term food shortage of 12-16
      day-old European shag nestlings kept under laboratory conditions. After 4 days on
      a weight maintenance diet, the resting metabolic rate (RMR) of diet-restricted
      nestlings was 36.5% lower compared with control fed nestlings, after controlling
      for body mass. This response was accompanied by a reduction in body temperature
      (T(b)) and by reductions in the size of several visceral organs, muscles and
      lipid stores, while the overall structural growth was maintained almost in line
      with the age-specific growth rate of controls. Hence, the pattern of energy
      allocation reflected a very high priority to structural growth at the expense of
      visceral organs, lipid deposits and muscles. The reduced T(b) and size of the
      liver served as important physiological processes behind the observed reductions
      in RMR. We discuss the possible adaptive significance of this differential
      developmental plasticity during temporal food shortage. This is the first study
      of avian developmental plasticity to report substantial energy saving in
      combination with a high structural growth rate.

PMID- 15498953
TI  - Calcium handling in Sparus auratus: effects of water and dietary calcium levels
      on mineral composition, cortisol and PTHrP levels.
AB  - Juvenile gilthead sea bream (Sparus auratus L.; 10-40 g body mass) were
      acclimatized in the laboratory to full strength (34 per thousand) or dilute (2.5
      per thousand) seawater and fed normal, calcium-sufficient or calcium-deficient
      diet for nine weeks. Mean growth rate, whole-body calcium and phosphorus content
      and accumulation rates were determined, as well as plasma levels of ionic and
      total calcium, cortisol and parathyroid hormone related protein (PTHrP; a
      hypercalcemic hormone in fish). When confronted with limited calcium access (low
      salinity and calcium-deficient diet), sea bream show growth arrest. Both plasma
      cortisol and PTHrP increase when calcium is limited in water or diet, and a
      positive relationship was found between plasma PTHrP and plasma ionic calcium
      (R(2)=0.29, N=18, P<0.05). Furthermore, a strong correlation was found between
      net calcium and phosphorus accumulation (R(2)=0.92, N=16, P<0.01) and between
      body mass and whole-body calcium (R(2)=0.84, N=25, P<0.01) and phosphorus
      (R(2)=0.88, N=24, P<0.01) content. Phosphorus accumulation is strongly calcium
      dependent, as phosphorus accumulation decreases in parallel to calcium
      accumulation when the diet is calcium deficient but phosphorus sufficient. We
      conclude that PTHrP and cortisol are involved in the regulation of the
      hydromineral balance of these fish, with growth-related calcium accumulation as
      an important target.

PMID- 15498955
TI  - Presence and properties of cellulase and hemicellulase enzymes of the gecarcinid
      land crabs Gecarcoidea natalis and Discoplax hirtipes.
AB  - Digestive juice from the herbivorous gecarcinid land crabs Gecarcoidea natalis
      and Discoplax hirtipes exhibited total cellulase activity and activities of two
      cellulase enzymes; endo-beta-1,4-glucanase and beta-1,4-glucosidase. These
      enzymes hydrolysed native cellulose to glucose. The digestive juice of both
      species also contained laminarinase, licheninase and xylanase, which hydrolysed
      laminarin, lichenin and xylan, respectively, to component sugars. The pH optima
      of beta-1,4-glucosidase, endo-beta-1,4-glucanase and total cellulase from G.
      natalis were 4-5.5, 5.5 and 5.5-7, respectively. In the digestive juice from D.
      hirtipes, the corresponding values were 4-7, 5.5-7 and 4-9, respectively. The pH
      of the digestive juice was 6.69+/-0.03 for G. natalis and 6.03+/-0.04 for D.
      hirtipes and it is likely that the cellulases operate near maximally in vivo. In
      G. natalis, total cellulase activity and endo-beta-1,4-glucanase activity were
      higher than in D. hirtipes, and the former species can thus hydrolyse cellulose
      more rapidly. beta-1,4-glucosidase from G. natalis was inhibited less by glucono
      d-lactone (K(i)=11.12 mmol l(-1)) than was the beta-1,4-glucosidase from D.
      hirtipes (K(i)=4.53 mmol l(-1)). The greater resistance to inhibition by the beta
      1,4-glucosidase from G. natalis may contribute to the efficiency of the cellulase
      system in vivo by counteracting the effects of product inhibition and possibly
      dietary tannins. The activity of beta-1,4-glucosidase in the digestive juice of
      D. hirtipes was higher than that of G. natalis.

PMID- 15498954
TI  - Ontogeny of the gut motility control system in zebrafish Danio rerio embryos and
      larvae.
AB  - Using digital motion analysis, the ontogeny of the cholinergic, tachykinin and
      pituitary adenylate cyclase-activating polypeptide (PACAP) control systems was
      studied in zebrafish Danio rerio larvae, in vivo. For the first time we show that
      the regular propagating anterograde waves that occur in the zebrafish larval gut
      before and around the onset [at 5-6 days post fertilization (d.p.f.)] of feeding
      are modulated by acetylcholine or atropine, PACAP and NKA (neurokinin A). At 3
      d.p.f., when no spontaneous motility has developed, application of acetylcholine
      did not affect the gut. However, at 4 d.p.f., acetylcholine increased and
      atropine reduced the frequency of propagating anterograde waves. At 5 d.p.f., NKA
      increased and PACAP reduced the wave frequency. This suggests that both
      excitatory and inhibitory pathways develop at an early stage in the gut,
      independent of exogenous feeding. Immunohistochemistry established the presence
      of gut neurons expressing PACAP and NKA in the proximal part of the developing
      gut from the first stage investigated (2 d.p.f.) and before regular motility was
      observed. 1 d.p.f. (PACAP) or 2 d.p.f. (NKA) stages later the whole gut was
      innervated. This supports physiological results that gut motility is under
      neuronal control during the period when regular motility patterns develop.

PMID- 15498956
TI  - The effect of substrate on the efficacy of seismic courtship signal transmission
      in the jumping spider Habronattus dossenus (Araneae: Salticidae).
AB  - The jumping spider Habronattus dossenus Griswold 1987 (Salticidae) communicates
      using seismic signals during courtship and can be found on rocks, sand and leaf
      litter. We examined the filtering properties of, and tested the efficacy of male
      courtship signals on, these natural substrates. These substrates have drastically
      different filtering properties at the distances at which the males court. Rocks
      sharply attenuated all frequencies, with considerable variability among different
      rocks. Desert sand showed band-pass properties, attenuating frequencies contained
      in the animal's signal. Leaf litter passed all frequencies and was the most
      favourable signalling environment. In behavioural trials, the proportion of males
      mating successfully was significantly higher on leaf litter than on rocks or
      desert sand. Males did not modify their courtship behaviour on different
      substrates. Therefore, the effectiveness of male courtship seismic signals
      appears to be strongly constrained by the available substratum resources.

PMID- 15498957
TI  - Elevated intra-abdominal pressure limits venous return during exercise in Varanus
      exanthematicus.
AB  - The effects of treadmill exercise on components of the cardiovascular (venous
      return, heart rate, arterial blood pressure) and respiratory systems (minute
      ventilation, tidal volume, breathing frequency, oxygen consumption, carbon
      dioxide production) and intra-abdominal pressure were investigated in the
      Savannah monitor lizard, Varanus exanthematicus B., at 35 degrees C. Compared
      with resting conditions, treadmill exercise significantly increased lung
      ventilation, gular pumping, intra-abdominal pressure, mean arterial blood
      pressure and venous return (blood flow in the post caval vein). However, venous
      return declines at high levels of activity, and mean arterial pressure and venous
      return did not attain peak values until the recovery period, immediately
      following activity. Elevating intra-abdominal pressure in resting lizards (via
      saline infusion) resulted in significant reductions in venous return when the
      transmural pressure of the post caval vein became negative (i.e. when intra
      abdominal pressure exceeded central venous pressure). Together these results
      suggest that increments in intra-abdominal pressure compress the large abdominal
      veins and inhibit venous return. During locomotion, the physical compression of
      the large abdominal veins may represent a significant limitation to cardiac
      output and maximal oxygen consumption in lizards.

PMID- 15498958
TI  - Sound localization in a small passerine bird: discrimination of azimuth as a
      function of head orientation and sound frequency.
AB  - Sound localization is critical to communication when signalers are distributed
      widely in space and when reverberations that accumulate over distance might
      otherwise degrade temporal patterns in vocalizations. We readdress the accuracy
      with which a small passerine bird, the eastern towhee, Pipilo erythrophthalmus
      L., is able to resolve azimuth in the field. We then report results from two
      alternative forced-choice (2AFC) experiments in which three of four subjects were
      able to discriminate an estimated speaker separation angle of approximately 7
      degrees . Subjects oriented laterally when discriminating azimuth in the 2AFC
      task and each subject preferred a different head orientation. Side biases
      occurred as a function of head orientation and, as a consequence, we conducted a
      second 2AFC experiment in which subjects were required to discriminate between
      two closely spaced lights. Subjects oriented similarly in this visual task,
      however, side biases did not occur as a function of head orientation. Despite
      side biases in the auditory task, performance generally declined when subjects
      were played tones with frequencies near approximately 3 kHz.

PMID- 15498960
TI  - The role of drag in insect hovering.
AB  - Studies of insect flight have focused on aerodynamic lift, both in quasi-steady
      and unsteady regimes. This is partly influenced by the choice of hovering motions
      along a horizontal stroke plane, where aerodynamic drag makes no contribution to
      the vertical force. In contrast, some of the best hoverers--dragonflies and
      hoverflies--employ inclined stroke planes, where the drag in the down- and
      upstrokes does not cancel each other. Here, computation of an idealized dragonfly
      wing motion shows that a dragonfly uses drag to support about three quarters of
      its weight. This can explain an anomalous factor of four in previous estimates of
      dragonfly lift coefficients, where drag was assumed to be small. To investigate
      force generation and energy cost of hovering flight using different combination
      of lift and drag, I study a family of wing motion parameterized by the inclined
      angle of the stroke plane. The lift-to-drag ratio is no longer a measure of
      efficiency, except in the case of horizontal stroke plane. In addition, because
      the flow is highly stalled, lift and drag are of comparable magnitude, and the
      aerodynamic efficiency is roughly the same up to an inclined angle about 60
      degrees , which curiously agrees with the angle observed in dragonfly flight.
      Finally, the lessons from this special family of wing motion suggests a strategy
      for improving efficiency of normal hovering, and a unifying view of different
      wing motions employed by insects.

PMID- 15498959
TI  - Conservation of capa peptide-induced nitric oxide signalling in Diptera.
AB  - In D. melanogaster Malpighian (renal) tubules, the capa peptides stimulate
      production of nitric oxide (NO) and guanosine 3', 5'-cyclic monophosphate (cGMP),
      resulting in increased fluid transport. The roles of NO synthase (NOS), NO and
      cGMP in capa peptide signalling were tested in several other insect species of
      medical relevance within the Diptera (Aedes aegypti, Anopheles stephensi and
      Glossina morsitans) and in one orthopteran out-group, Schistocerca gregaria. NOS
      immunoreactivity was detectable by immunocytochemistry in tubules from all
      species studied. D. melanogaster, A. aegypti and A. stephensi express NOS in only
      principal cells, whereas G. morsitans and S. gregaria show more general NOS
      expression in the tubule. Measurement of associated NOS activity (NADPH
      diaphorase) shows that both D. melanogaster capa-1 and the two capa peptides
      encoded in the A. gambiae genome, QGLVPFPRVamide (AngCAPA-QGL) and
      GPTVGLFAFPRVamide (AngCAPA-GPT), all stimulate NOS activity in D. melanogaster,
      A. aegypti, A. stephensi and G. morsitans tubules but not in S. gregaria.
      Furthermore, capa-stimulated NOS activity in all the Diptera was inhibited by the
      NOS inhibitor l-NAME. All capa peptides stimulate an increase in cGMP content
      across the dipteran species, but not in the orthopteran S. gregaria. Similarly,
      all capa peptides tested stimulate fluid secretion in D. melanogaster, A.
      aegypti, A. stephensi and G. morsitans tubules but are either without effect or
      are inhibitory on S. gregaria. Consistent with these results, the Drosophila capa
      receptor was shown to be expressed in Drosophila tubules, and its closest
      Anopheles homologue was shown to be expressed in Anopheles tubules. Thus, we
      provide the first demonstration of physiological roles for two putative A.
      gambiae neuropeptides. We also demonstrate neuropeptide modulation of fluid
      secretion in tsetse tubule for the first time. Finally, we show the generality of
      capa peptide action, to stimulate NO/cGMP signalling and increase fluid
      transport, across the Diptera, but not in the more primitive Orthoptera.

PMID- 15498961
TI  - Cardiorespiratory and tissue adenosine responses to hypoxia and reoxygenation in
      the short-horned sculpin Myoxocephalus scorpius.
AB  - Adenosine is a product of adenylate phosphate breakdown that can exert protective
      effects on tissues during energy limitation. Accumulation of cardiac adenosine
      under hypoxia is well documented in mammals but has not been shown in fish.
      Adenosine content was measured in heart and brain tissue from short-horned
      sculpin Myoxocephalus scorpius L. exposed to acute hypoxia and to graded hypoxia
      and reoxygenation at 8 degrees C. Cardiorespiratory parameters were recorded
      along with plasma lactate, K(+), Ca(2+) and Na(+) levels and their relationship
      to adenosine levels investigated. Sculpin exhibited a large bradycardia during
      hypoxia, with a concomitant drop in cardiac output that recovers fully with
      reoxygenation. Ventilation rate also declined with hypoxia, suggesting a
      depression of activity. Plasma lactate concentration was significantly elevated
      after 4 h at 2.0 mg l(-1) dissolved oxygen while K(+) levels increased during
      acute hypoxia. Adenosine levels were maintained in heart under acute and graded
      hypoxia. Brain levels fluctuated under hypoxia and showed no change with
      reoxygenation. It is concluded that a depression of cardiac activity in
      conjunction with an adequate anaerobic metabolism allow sculpin to avoid
      excessive adenosine accumulation under conditions of moderate hypoxia. Cardiac
      adenosine levels decreased and plasma K(+) levels and heart rate increased
      significantly at reoxygenation.

PMID- 15498962
TI  - Adjusting muscle function to demand: joint work during acceleration in wild
      turkeys.
AB  - We measured the net work performed at hind limb joints in running turkeys to
      determine the source of mechanical power for acceleration. We tested the
      hypothesis that net mechanical work per step increases in proportion to
      acceleration at all four major hind limb joints (hip, knee, ankle and
      tarsometatarsal-phalangeal joint). This hypothesis was based on the idea that all
      hind limb muscles should contribute mechanical work to maximize performance
      during accelerations, and a previous study that indicated the mechanical power
      output of the entire turkey hind limb musculature was remarkably high. We used
      high-speed video and force-plate measurements to measure joint moment, velocity
      and power output during single foot-contacts of running accelerations. By
      measuring steps in which the animals were relatively more or less motivated to
      accelerate, we obtained data for a range of accelerations, all at approximately
      the same running speed. Net joint work per step increased at the hip and ankle as
      a function of acceleration. Hip net work per unit body mass was 0.12+/-0.09 J kg(
      1) averaged over the five lowest accelerations (-0.22+/-0.08 m s(-2)), and 0.87+/
      0.20 J kg(-1) for the five highest accelerations (4.86+/-0.27 m s(-2)). Ankle
      work was -0.21+/-0.11 J kg(-1) for the lowest accelerations and 0.71+/-0.28 J kg(
      1) for the highest. The high work output at the ankle is consistent with the idea
      that elastic mechanisms function to increase muscle work during acceleration. The
      work performed at the knee and tarsometatarsal-phalangeal joint was independent
      of acceleration in a step. These results support the idea that hip and ankle
      extensors contribute significantly to the work necessary to accelerate the body.
      We also measured the change in joint moment and angular excursion with
      acceleration to determine whether the mechanism for increasing work output at a
      joint involved an increase in muscle force or muscle shortening. The increase in
      joint work at the hip and ankle resulted almost entirely from an increase in
      joint angular excursion during stance. Hip extension increased by more than
      threefold from the lowest to the highest accelerations, and the angular excursion
      of the ankle increased from -24.8+/-4.7 degrees (net flexion) at the lowest
      accelerations to 33.0+/-12.8 degrees (net extension) at the highest
      accelerations. Mean stance joint moment was unchanged with acceleration at the
      ankle and increased by approximately 35% at the hip across the range of
      accelerations. These patterns of joint moment and excursion indicate that turkeys
      increase mechanical work for acceleration primarily by increasing muscle
      shortening, rather than muscle force.

PMID- 15498963
TI  - Heterogeneity of human nasal vascular and sinusoidal endothelial cells from the
      inferior turbinate.
AB  - The vast heterogeneity of endothelial cells (EC) in various organs necessitates
      isolation of EC from the relevant organs when defining mechanisms of site
      specific pathologies. We report a novel finding that describes the presence of
      two heterogeneous populations of human nasal microvascular EC isolated from the
      inferior turbinate. Light and electron microscopy, flow cytometric analysis, and
      immunocytochemistry analysis demonstrated that one EC population exhibited the
      classic vascular endothelial markers with cobblestone-like morphology, whereas
      the other was sinusoidal with fusiform morphology. The sinusoidal EC (SEC) lacked
      surface expression of the endothelial markers CD31 and E-selectin, were
      discontinuous, showed fenestrae and pinocytic vesicles, and did not form tight
      junctions. Gene expression analysis using microarray revealed significant but
      limited heterogeneity between the two cell types. Immunohistochemical staining of
      normal nasal biopsies confirmed the presence of two distinct populations of EC.
      We found that CD31 was exclusively expressed on vascular EC (VEC), whereas the
      molecule L-SIGN was mainly expressed on SEC. Both cell types formed capillary
      like tubules in matrigel in vitro. The two heterogeneous EC populations provide a
      unique in vitro system to study the biology of nasal VEC and SEC in normal
      conditions and in inflammatory processes in various nasal disorders.

PMID- 15498964
TI  - Blood pressure power within frequency range approximately 0.4 Hz in rat conforms
      to self-similar scaling following spinal cord transection.
AB  - This study quantified the effect of interrupting the descending input to the
      sympathetic preganglionic neurons on the dynamic behavior of arterial blood
      pressure (BP) in the unanesthetized rat. BP was recorded for approximately 4-h
      intervals in six rats in the neurally intact state and in the same animals after
      complete spinal cord transection (SCT) between T(4) and T(5). In the intact
      state, power within the frequency range of 0.35-0.45 Hz was 1.53 +/- 0.38
      mmHg(2)/Hz (mean +/- SD by fast Fourier transform). One week after SCT, power
      within this range decreased significantly (P < 0.05) to 0.43 +/- 0.62 mmHg(2)/Hz.
      To test for self-similarity before and after SCT, we analyzed data using a
      wavelet (i.e., functionally, a digital bandpass filter) tuned to be maximally
      sensitive to fluctuations with periods of approximately 2, 4, 8, 16, 32, or 64 s.
      In the control state, all fluctuations with periods of >/=4 s conformed to a
      "self-similar" (i.e., fractal) distribution. In marked contrast, the oscillations
      with a period of approximately 2 s (i.e., approximately 0.4 Hz) were
      significantly set apart from those at lower frequencies. One day and seven days
      after the complete SCT, however, the BP fluctuations at approximately 0.4 Hz now
      also conformed to the same self-similar behavior characteristic of the lower
      frequencies. We conclude that 1) an intact sympathetic nervous system endows that
      portion of the power spectrum centered around approximately 0.4 Hz with
      properties (e.g., a periodicity) that differ significantly from the self-similar
      behavior that characterizes the lower frequencies and 2) even within the
      relatively high frequency range at 0.4 Hz self-similarity is the "default"
      condition after sympathetic influences have been eliminated.

PMID- 15498965
TI  - Hypoxia induces major effects on cell cycle kinetics and protein expression in
      Drosophila melanogaster embryos.
AB  - Hypoxia induces a stereotypic response in Drosophila melanogaster embryos:
      depending on the time of hypoxia, embryos arrest cell cycle activity either at
      metaphase or just before S phase. To understand the mechanisms underlying hypoxia
      induced arrest, two kinds of experiments were conducted. First, embryos carrying
      a kinesin-green fluorescent protein construct, which permits in vivo confocal
      microscopic visualization of the cell cycle, showed a dose-response relation
      between O2 level and cell cycle length. For example, mild hypoxia (Po2
      approximately 55 Torr) had no apparent effect on cell cycle length, whereas
      severe hypoxia (Po2 approximately 25-35 Torr) or anoxia (Po2 = 0 Torr) arrested
      the cell cycle. Second, we utilized Drosophila embryos carrying a heat shock
      promoter driving the string (cdc25) gene (HS-STG3), which permits synchronization
      of embryos before the start of mitosis. Under conditions of anoxia, we induced a
      stabilization or an increase in the expression of several G1/S (e.g., dE2F1,
      RBF2) and G2/M (e.g., cyclin A, cyclin B, dWee1) proteins. This study suggests
      that, in fruit fly embryos, 1) there is a dose-dependent relationship between
      cell cycle length and O2 levels in fruit fly embryos, and 2) stabilized cyclin A
      and E2F1 are likely to be the mediators of hypoxia-induced arrest at metaphase
      and pre-S phase.

PMID- 15498966
TI  - Genetic AT1A receptor deficiency attenuates cold-induced hypertension.
AB  - The aim of this study was to test our hypotheses that AT1A receptors play a role
      in the pathogenesis of cold-induced hypertension (CIH) and in the cold-induced
      increase in drinking responses to ANG II. Two groups of wild-type (WT) and two
      groups of AT1A receptor gene knockout (AT1A-KO) mice were used (6/group). Blood
      pressures (BP) of the four groups were similar during the control period at room
      temperature (25 degrees C). After the control period, one group of WT and one
      group of AT1A-KO mice were exposed to cold (5 degrees C), while the remaining
      groups were kept at 25 degrees C. BP of the cold-exposed WT group elevated
      significantly within 1 wk of exposure to cold and increased gradually to a
      maximum level by week 5. However, there was only a slight increase in BP of the
      cold-exposed AT1A-KO group. The maximal cold-induced increase in BP (DeltaBP) is
      significantly less in AT1A-KO group (11 +/- 3 mmHg) than in WT group (49 +/- 6
      mmHg), indicating that AT1A receptor deficiency attenuates cold-induced elevation
      of BP. Interestingly, both WT and AT1A-KO mice developed cardiac and renal
      hypertrophy to the same extent. AT1A-KO caused a significant increase in urine
      and plasma levels of nitric oxide (NO), indicating that the renin-angiotensin
      system inhibits NO formation probably via AT1A receptors. Cold exposure inhibited
      endothelial NO synthase protein expressions and decreased urine and plasma levels
      of NO, which may be mediated partially by AT1A receptors. AT1A-KO completely
      abolished the cold-induced increase in drinking responses to ANG II. We conclude
      that 1) AT1A receptors play an essential role in the pathogenesis of CIH but not
      cardiac hypertrophy; 2) the role of AT1A receptors in CIH may be mediated
      partially by its inhibitory effect on the NO system; and 3) cold-induced increase
      in drinking response to ANG II is mediated by AT1A receptors.

PMID- 15498969
TI  - Election science.

PMID- 15498967
TI  - Cardiovascular actions of rattlesnake bradykinin ([Val1,Thr6]bradykinin) in the
      anesthetized South American rattlesnake Crotalus durissus terrificus.
AB  - Incubation of heat-denatured plasma from the rattlesnake Crotalus atrox with
      trypsin generated a bradykinin (BK) that contained two amino acid substitutions
      (Arg1 --> Val and Ser6 --> Thr) compared with mammalian BK. Bolus intra-arterial
      injections of synthetic rattlesnake BK (0.01-10 nmol/kg) into the anesthetized
      rattlesnake, Crotalus durissus terrificus, produced a pronounced and
      concentration-dependent increase in systemic vascular conductance (Gsys). This
      caused a fall in systemic arterial blood pressure (Psys) and an increase in blood
      flow. Heart rate and stroke volume also increased. This primary response was
      followed by a significant rise in Psys and pronounced tachycardia (secondary
      response). Pretreatment with N(G)-nitro-L-arginine methyl ester reduced the NK
      induced systemic vasodilatation, indicating that the effect is mediated through
      increased NO synthesis. The tachycardia associated with the late primary and
      secondary response to BK was abolished with propranolol and the systemic
      vasodilatation produced in the primary phase was also significantly attenuated by
      pretreatment, indicating that the responses are caused, at least in part, by
      release of cathecholamines and subsequent stimulation of beta-adrenergic
      receptors. In contrast, the pulmonary circulation was relatively unresponsive to
      BK.

PMID- 15498968
TI  - Dose-dependent effects of L-carnosine on the renal sympathetic nerve and blood
      pressure in urethane-anesthetized rats.
AB  - The physiological function of L-carnosine (beta-alanyl-L-histidine) synthesized
      in mammalian muscles has been unclear. Previously, we observed that intravenous
      (i.v.) injection of L-carnosine suppressed renal sympathetic nerve activity
      (RSNA) in urethane-anesthetized rats, and L-carnosine administered via the diet
      inhibited the elevation of blood pressure (BP) in deoxycorticosterone acetate
      salt hypertensive rats. To identify the mechanism, we examined effects of i.v. or
      intralateral cerebral ventricular (l.c.v.) injection of various doses of L
      carnosine on RSNA and BP in urethane-anesthetized rats. Lower doses (1 microg
      i.v.; 0.01 microg l.c.v.) of L-carnosine significantly suppressed RSNA and BP,
      whereas higher doses (100 microg i.v.; 10 microg l.c.v.) elevated RSNA and BP.
      Furthermore, we examined effects of antagonists of histaminergic (H1 and H3)
      receptors on L-carnosine-induced effects. When peripherally and centrally given,
      thioperamide, an H3 receptor antagonist, blocked RSNA and BP decreases induced by
      the lower doses of peripheral L-carnosine, whereas diphenhydramine, an H1
      receptor antagonist, inhibited increases induced by the higher doses of
      peripheral L-carnosine. Moreover, bilateral lesions of the hypothalamic
      suprachiasmatic nucleus eliminated both effects on RSNA and BP induced by the
      lower (1 microg) and higher (100 microg) doses of peripheral L-carnosine. These
      findings suggest that low-dose L-carnosine suppresses and high-dose L-carnosine
      stimulates RSNA and BP, that the suprachiasmatic nucleus and histaminergic nerve
      are involved in the activities, and that L-carnosine acts in the brain and
      possibly other organs.

PMID- 15498970
TI  - The roaming atom: straying from the reaction path in formaldehyde decomposition.
AB  - We present a combined experimental and theoretical investigation of formaldehyde
      (H2CO) dissociation to H2 and CO at energies just above the threshold for
      competing H elimination. High-resolution state-resolved imaging measurements of
      the CO velocity distributions reveal two dissociation pathways. The first
      proceeds through a well-established transition state to produce rotationally
      excited CO and vibrationally cold H2. The second dissociation pathway yields
      rotationally cold CO in conjunction with highly vibrationally excited H2. Quasi
      classical trajectory calculations performed on a global potential energy surface
      for H2CO suggest that this second channel represents an intramolecular hydrogen
      abstraction mechanism: One hydrogen atom explores large regions of the potential
      energy surface before bonding with the second H atom, bypassing the saddle point
      entirely.

PMID- 15498971
TI  - Earth tides can trigger shallow thrust fault earthquakes.
AB  - We show a correlation between the occurrence of shallow thrust earthquakes and
      the occurrence of the strongest tides. The rate of earthquakes varies from the
      background rate by a factor of 3 with the tidal stress. The highest correlation
      is found when we assume a coefficient of friction of mu = 0.4 for the crust,
      although we see good correlation for mu between 0.2 and 0.6. Our results quantify
      the effect of applied stress on earthquake triggering, a key factor in
      understanding earthquake nucleation and cascades whereby one earthquake triggers
      others.

PMID- 15498973
TI  - Compensated deleterious mutations in insect genomes.
AB  - Relatively little is known about the importance of amino acid interactions in
      protein and phenotypic evolution. Here we examine whether mutations that are
      pathogenic in Drosophila melanogaster become fixed via epistasis in other
      Dipteran genomes. Overall divergence at pathogenic amino acid sites is reduced.
      However, approximately 10% of the substitutions at these sites carry the exact
      same pathogenic amino acid found in D. melanogaster mutants. Hence compensatory
      mutation(s) must have evolved. Surprisingly, the fraction 10% is not affected by
      phylogenetic distance. These results support a selection-driven process that
      allows compensated amino acid substitutions to become rapidly fixed in taxa with
      large populations.

PMID- 15498972
TI  - A cluster of metabolic defects caused by mutation in a mitochondrial tRNA.
AB  - Hypertension and dyslipidemia are risk factors for atherosclerosis and occur
      together more often than expected by chance. Although this clustering suggests
      shared causation, unifying factors remain unknown. We describe a large kindred
      with a syndrome including hypertension, hypercholesterolemia, and hypomagnesemia.
      Each phenotype is transmitted on the maternal lineage with a pattern indicating
      mitochondrial inheritance. Analysis of the mitochondrial genome of the maternal
      lineage identified a homoplasmic mutation substituting cytidine for uridine
      immediately 5' to the mitochondrial transfer RNA(Ile) anticodon. Uridine at this
      position is nearly invariate among transfer RNAs because of its role in
      stabilizing the anticodon loop. Given the known loss of mitochondrial function
      with aging, these findings may have implications for the common clustering of
      these metabolic disorders.

PMID- 15498974
TI  - Genomics and drug toxicity.

PMID- 15498975
TI  - Bioethics. Stem cell researchers mull ideas for self-regulation.

PMID- 15498976
TI  - Malaria. A complex new vaccine shows promise.

PMID- 15498977
TI  - Planetary science. Flipped switch sealed the fate of Genesis spacecraft.

PMID- 15498978
TI  - Canada. Martin backs science academy.

PMID- 15498979
TI  - Bioterrorism and the courts. Butler appeals conviction, risking longer sentence.

PMID- 15498980
TI  - Infectious diseases. Bird flu infected 1000, Dutch researchers say.

PMID- 15498981
TI  - Biocontainment. 1918 flu experiments spark concerns about biosafety.

PMID- 15498982
TI  - General relativity. Swiveling satellites see Earth's relativistic wake.

PMID- 15498983
TI  - Medicine. Metabolic defects tied to mitochondrial gene.

PMID- 15498984
TI  - Physics. Researchers build quantum info bank by writing on the clouds.

PMID- 15498985
TI  - National Institutes of Health. Male sweep of new award raises questions of bias.

PMID- 15498986
TI  - National Science Foundation. End of cost sharing could boost competition.

PMID- 15498988
TI  - Climate change. A few good climate shifters.

PMID- 15498987
TI  - Immunology. Policing the immune system.

PMID- 15498989
TI  - Behavioral science. NIMH takes a new tack, upsetting behavioral researchers.

PMID- 15498990
TI  - Infectious diseases. Hawaii girds itself for arrival of West Nile virus.

PMID- 15498991
TI  - Another question for Bush and Kerry.

PMID- 15498992
TI  - Struggling to attend U.S. meetings.

PMID- 15498993
TI  - Is Bedout an impact crater? Take 1.

PMID- 15498994
TI  - Is Bedout an impact crater? Take 2.

PMID- 15498995
TI  - The next step for Kennewick Man.

PMID- 15498996
TI  - Comment on "Bedout: a possible end-Permian impact crater offshore of Northwestern
      Australia".

PMID- 15498998
TI  - Nuclear safety. Brazil's nuclear puzzle.

PMID- 15498999
TI  - Chemistry. A fresh look at electron hydration.

PMID- 15499000
TI  - Genetics. The critical region in trisomy 21.

PMID- 15499001
TI  - Plant biology. A plant ABC transporter takes the lotus seat.

PMID- 15499002
TI  - Chemistry. Redesigning genetics.

PMID- 15499004
TI  - Getting the noise out of gene arrays.

PMID- 15499005
TI  - Searching for the genome's second code.

PMID- 15499006
TI  - A fast and furious hunt for gene regulators.

PMID- 15499007
TI  - The ENCODE (ENCyclopedia Of DNA Elements) Project.
AB  - The ENCyclopedia Of DNA Elements (ENCODE) Project aims to identify all functional
      elements in the human genome sequence. The pilot phase of the Project is focused
      on a specified 30 megabases (approximately 1%) of the human genome sequence and
      is organized as an international consortium of computational and laboratory-based
      scientists working to develop and apply high-throughput approaches for detecting
      all sequence elements that confer biological function. The results of this pilot
      phase will guide future efforts to analyze the entire human genome.

PMID- 15499008
TI  - Systems biology and new technologies enable predictive and preventative medicine.
AB  - Systems approaches to disease are grounded in the idea that disease-perturbed
      protein and gene regulatory networks differ from their normal counterparts; we
      have been pursuing the possibility that these differences may be reflected by
      multiparameter measurements of the blood. Such concepts are transforming current
      diagnostic and therapeutic approaches to medicine and, together with new
      technologies, will enable a predictive and preventive medicine that will lead to
      personalized medicine.

PMID- 15499009
TI  - Gene order and dynamic domains.
AB  - When considering the daunting complexity of eukaryotic genomes, some comfort can
      be found in the fact that the human genome may contain only 30,000 to 40,000
      genes. Moreover, growing evidence suggests that genomes may be organized in such
      a way as to take advantage of space. A gene's location in the linear DNA sequence
      and its position in the three-dimensional nucleus can both be important in its
      regulation. Contrary to prevailing notions in this postgenomic era, the
      bacteriophage lambda, a paragon of simplicity, may still have a few things to
      teach us with respect to these facets of nonrandom genomes.

PMID- 15499010
TI  - Cis-acting regulatory variation in the human genome.
AB  - The systematic screening of the human genome for genetic variants that affect
      gene regulation should advance our fundamental understanding of phenotypic
      diversity and lead to the identification of alleles that modify disease risk.
      There are several challenges in localizing regulatory polymorphisms, including
      the wide spectrum of cis-acting regulatory mechanisms, the inconsistent effects
      of regulatory variants in different tissues, and the difficulty in isolating the
      causal variants that are in linkage disequilibrium with many other variants. We
      discuss the current state of knowledge and technologies used for mapping and
      characterizing genetic variation controlling human gene expression.

PMID- 15499011
TI  - A precocial avian embryo from the Lower Cretaceous of China.
AB  - An embryo of an enantiornithine bird has been recovered from the Lower Cretaceous
      rocks of Liaoning, in northeast China. The bird has a nearly complete articulated
      skeleton with feather sheet impressions and is enclosed in egg-shaped confines.
      The tucking posture of the skeleton suggests that the embryo had attained the
      final stage of development. The presence of well-developed wing and tail feather
      sheets indicates a precocial developmental mode, supporting the hypothesis that
      precocial birds appeared before altricial birds.

PMID- 15499012
TI  - A gene expression map for the euchromatic genome of Drosophila melanogaster.
AB  - We used a maskless photolithography method to produce DNA oligonucleotide
      microarrays with unique probe sequences tiled throughout the genome of Drosophila
      melanogaster and across predicted splice junctions. RNA expression of protein
      coding and nonprotein coding sequences was determined for each major stage of the
      life cycle, including adult males and females. We detected transcriptional
      activity for 93% of annotated genes and RNA expression for 41% of the probes in
      intronic and intergenic sequences. Comparison to genome-wide RNA interference
      data and to gene annotations revealed distinguishable levels of expression for
      different classes of genes and higher levels of expression for genes with
      essential cellular functions. Differential splicing was observed in about 40% of
      predicted genes, and 5440 previously unknown splice forms were detected. Genes
      within conserved regions of synteny with D. pseudoobscura had highly correlated
      expression; these regions ranged in length from 10 to 900 kilobase pairs. The
      expressed intergenic and intronic sequences are more likely to be evolutionarily
      conserved than nonexpressed ones, and about 15% of them appear to be
      developmentally regulated. Our results provide a draft expression map for the
      entire nonrepetitive genome, which reveals a much more extensive and diverse set
      of expressed sequences than was previously predicted.

PMID- 15499013
TI  - Quantum-to-classical transition with single-photon-added coherent states of
      light.
AB  - Single-photon-added coherent states are the result of the most elementary
      amplification process of classical light fields by a single quantum of
      excitation. Being intermediate between a single-photon Fock state (fully quantum
      mechanical) and a coherent (classical) one, these states offer the opportunity to
      closely follow the smooth transition between the particle-like and the wavelike
      behavior of light. We report the experimental generation of single-photon-added
      coherent states and their complete characterization by quantum tomography.
      Besides visualizing the evolution of the quantum-to-classical transition, these
      states allow one to witness the gradual change from the spontaneous to the
      stimulated regimes of light emission.

PMID- 15499014
TI  - Quantum state transfer between matter and light.
AB  - We report on the coherent quantum state transfer from a two-level atomic system
      to a single photon. Entanglement between a single photon (signal) and a two
      component ensemble of cold rubidium atoms is used to project the quantum memory
      element (the atomic ensemble) onto any desired state by measuring the signal in a
      suitable basis. The atomic qubit is read out by stimulating directional emission
      of a single photon (idler) from the (entangled) collective state of the ensemble.
      Faithful atomic memory preparation and readout are verified by the observed
      correlations between the signal and the idler photons. These results enable
      implementation of distributed quantum networking.

PMID- 15499015
TI  - Electric field effect in atomically thin carbon films.
AB  - We describe monocrystalline graphitic films, which are a few atoms thick but are
      nonetheless stable under ambient conditions, metallic, and of remarkably high
      quality. The films are found to be a two-dimensional semimetal with a tiny
      overlap between valence and conductance bands, and they exhibit a strong
      ambipolar electric field effect such that electrons and holes in concentrations
      up to 10(13) per square centimeter and with room-temperature mobilities of
      approximately 10,000 square centimeters per volt-second can be induced by
      applying gate voltage.

PMID- 15499016
TI  - Mycobacterial Ku and ligase proteins constitute a two-component NHEJ repair
      machine.
AB  - In mammalian cells, repair of DNA double-strand breaks (DSBs) by nonhomologous
      end-joining (NHEJ) is critical for genome stability. Although the end-bridging
      and ligation steps of NHEJ have been reconstituted in vitro, little is known
      about the end-processing reactions that occur before ligation. Recently,
      functionally homologous end-bridging and ligation activities have been identified
      in prokarya. Consistent with its homology to polymerases and nucleases, we
      demonstrate that DNA ligase D from Mycobacterium tuberculosis (Mt-Lig) possesses
      a unique variety of nucleotidyl transferase activities, including gap-filling
      polymerase, terminal transferase, and primase, and is also a 3' to 5'
      exonuclease. These enzyme activities allow the Mt-Ku and Mt-Lig proteins to join
      incompatible DSB ends in vitro, as well as to reconstitute NHEJ in vivo in yeast.
      These results demonstrate that prokaryotic Ku and ligase form a bona fide NHEJ
      system that encodes all the recognition, processing, and ligation activities
      required for DSB repair.

PMID- 15499017
TI  - Elemental and redox analysis of single bacterial cells by x-ray microbeam
      analysis.
AB  - High-energy x-ray fluorescence measurements were used to make elemental maps and
      qualitative chemical analyses of individual Pseudomonas fluorescens strain NCIMB
      11764 cells. Marked differences between planktonic and adhered cells were seen in
      the morphology, elemental composition, and sensitivity to Cr(VI) of hydrated
      cells at spatial scales of 150 nm. This technology can be applied to natural
      geomicrobiological systems.

PMID- 15499018
TI  - A chromosome 21 critical region does not cause specific Down syndrome phenotypes.
AB  - The "Down syndrome critical region" (DSCR) is a chromosome 21 segment purported
      to contain genes responsible for many features of Down syndrome (DS), including
      craniofacial dysmorphology. We used chromosome engineering to create mice that
      were trisomic or monosomic for only the mouse chromosome segment orthologous to
      the DSCR and assessed dysmorphologies of the craniofacial skeleton that show
      direct parallels with DS in mice with a larger segmental trisomy. The DSCR genes
      were not sufficient and were largely not necessary to produce the facial
      phenotype. These results refute specific predictions of the prevailing hypothesis
      of gene action in DS.

PMID- 15499019
TI  - In silico genetics: identification of a functional element regulating H2-Ealpha
      gene expression.
AB  - Computational tools can markedly accelerate the rate at which murine genetic
      models can be analyzed. We developed a computational method for mapping
      phenotypic traits that vary among inbred strains onto haplotypic blocks. This
      method correctly predicted the genetic basis for strain-specific differences in
      several biologically important traits. It was also used to identify an allele
      specific functional genomic element regulating H2-Ealpha gene expression. This
      functional element, which contained the binding sites for YY1 and a second
      transcription factor that is probably serum response factor, is located within
      the first intron of the H2-Ealpha gene. This computational method will greatly
      improve our ability to identify the genetic basis for a variety of phenotypic
      traits, ranging from qualitative trait information to quantitative gene
      expression data, which vary among inbred mouse strains.

PMID- 15499020
TI  - The PP2A-associated protein alpha4 is an essential inhibitor of apoptosis.
AB  - Despite evidence that protein kinases are regulators of apoptosis, a specific
      role for phosphatases in regulating cell survival has not been established. Here
      we show that alpha4, a noncatalytic subunit of protein phosphatase 2A (PP2A), is
      required to repress apoptosis in murine cells. alpha4 is a nonredundant regulator
      of the dephosphorylation of the transcription factors c-Jun and p53. As a result
      of alpha4 deletion, multiple proapoptotic genes were transcribed. Either
      inhibition of new protein synthesis or Bcl-xL overexpression suppressed apoptosis
      initiated by alpha4 deletion. Thus, mammalian cell viability depends on
      repression of transcription-initiated apoptosis mediated by a component of PP2A.

PMID- 15499021
TI  - A network of control mediated by regulator of calcium/calmodulin-dependent
      signaling.
AB  - Calmodulin (CaM) is a major effector for the intracellular actions of Ca2+ in
      nearly all cell types. We identified a CaM-binding protein, designated regulator
      of calmodulin signaling (RCS). G protein-coupled receptor (GPCR)-dependent
      activation of protein kinase A (PKA) led to phosphorylation of RCS at Ser55 and
      increased its binding to CaM. Phospho-RCS acted as a competitive inhibitor of CaM
      dependent enzymes, including protein phosphatase 2B (PP2B, also called
      calcineurin). Increasing RCS phosphorylation blocked GPCR- and PP2B-mediated
      suppression of L-type Ca2+ currents in striatal neurons. Conversely, genetic
      deletion of RCS significantly increased this modulation. Through a molecular
      mechanism that amplifies GPCR- and PKA-mediated signaling and attenuates GPCR-
      and PP2B-mediated signaling, RCS synergistically increases the phosphorylation of
      key proteins whose phosphorylation is regulated by PKA and PP2B.

PMID- 15499022
TI  - Plant cuticular lipid export requires an ABC transporter.
AB  - A waxy protective cuticle coats all primary aerial plant tissues. Its synthesis
      requires extensive export of lipids from epidermal cells to the plant surface.
      Arabidopsis cer5 mutants had reduced stem cuticular wax loads and accumulated
      sheetlike inclusions in the cytoplasm of wax-secreting cells. These inclusions
      represented abnormal deposits of cuticular wax and resembled inclusions found in
      a human disorder caused by a defective peroxisomal adenosine triphosphate binding
      cassette (ABC) transporter. We found that the CER5 gene encodes an ABC
      transporter localized in the plasma membrane of epidermal cells and conclude that
      it is required for wax export to the cuticle.

PMID- 15499023
TI  - Oscillations in NF-kappaB signaling control the dynamics of gene expression.
AB  - Signaling by the transcription factor nuclear factor kappa B (NF-kappaB) involves
      its release from inhibitor kappa B (IkappaB) in the cytosol, followed by
      translocation into the nucleus. NF-kappaB regulation of IkappaBalpha
      transcription represents a delayed negative feedback loop that drives
      oscillations in NF-kappaB translocation. Single-cell time-lapse imaging and
      computational modeling of NF-kappaB (RelA) localization showed asynchronous
      oscillations following cell stimulation that decreased in frequency with
      increased IkappaBalpha transcription. Transcription of target genes depended on
      oscillation persistence, involving cycles of RelA phosphorylation and
      dephosphorylation. The functional consequences of NF-kappaB signaling may thus
      depend on number, period, and amplitude of oscillations.

PMID- 15499024
TI  - Calcium dynamics in cortical astrocytes and arterioles during neurovascular
      coupling.
AB  - Neuronal activity in the brain is thought to be coupled to cerebral arterioles
      (functional hyperemia) through Ca2+ signals in astrocytes. Although functional
      hyperemia occurs rapidly, within seconds, such rapid signaling has not been
      demonstrated in situ, and Ca2+ measurements in parenchymal arterioles are still
      lacking. Using a laser scanning confocal microscope and fluorescence Ca2+
      indicators, we provide the first evidence that in a brain slice preparation,
      increased neuronal activity by electrical stimulation (ES) is rapidly signaled,
      within seconds, to cerebral arterioles and is associated with astrocytic Ca2+
      waves. Smooth muscle cells in parenchymal arterioles exhibited Ca2+ and diameter
      oscillations ("vasomotion") that were rapidly suppressed by ES. The neuronal
      mediated Ca2+ rise in cortical astrocytes was dependent on intracellular
      (inositol trisphosphate [IP3]) and extracellular voltage-dependent Ca2+ channel
      sources. The Na+ channel blocker tetrodotoxin prevented the rise in astrocytic
      [Ca2+]i and the suppression of Ca2+ oscillations in parenchymal arterioles to ES,
      indicating that neuronal activity was necessary for both events. Activation of
      metabotropic glutamate receptors in astrocytes significantly decreased the
      frequency of Ca2+ oscillations in parenchymal arterioles. This study supports the
      concept that astrocytic Ca2+ changes signal the cerebral microvasculature and
      indicate the novel concept that this communication occurs through the suppression
      of arteriolar [Ca2+]i oscillations and corresponding vasomotion. The full text of
      this article is available online at http://circres.ahajournals.org.

PMID- 15499025
TI  - Caveolae localize protein kinase A signaling to arterial ATP-sensitive potassium
      channels.
AB  - Arterial ATP-sensitive K+ (K(ATP)) channels are critical regulators of vascular
      tone, forming a focal point for signaling by many vasoactive transmitters that
      alter smooth muscle contractility and so blood flow. Clinically, these channels
      form the target of antianginal and antihypertensive drugs, and their genetic
      disruption leads to hypertension and sudden cardiac death through coronary
      vasospasm. However, whereas the biochemical basis of K(ATP) channel modulation is
      well-studied, little is known about the structural or spatial organization of the
      signaling pathways that converge on these channels. In this study, we use
      discontinuous sucrose density gradients and Western blot analysis to show that
      K(ATP) channels localize with an upstream signaling partner, adenylyl cyclase, to
      smooth muscle membrane fractions containing caveolin, a protein found exclusively
      in cholesterol and sphingolipid-enriched membrane invaginations known as
      caveolae. Furthermore, we show that an antibody against the K(ATP) pore-forming
      subunit, Kir6.1 co-immunoprecipitates caveolin from arterial homogenates,
      suggesting that Kir6.1 and caveolin exist together in a complex. To assess
      whether the colocalization of K(ATP) channels and adenylyl cyclase to smooth
      muscle caveolae has functional significance, we disrupt caveolae with the
      cholesterol-depleting agent, methyl-beta-cyclodextrin. This reduces the cAMP
      dependent protein kinase A-sensitive component of whole-cell K(ATP) current,
      indicating that the integrity of caveolae is important for adenylyl cyclase
      mediated channel modulation. These results suggest that to be susceptible to
      protein kinase A-dependent activation, arterial K(ATP) channels need to be
      localized in the same lipid compartment as adenylyl cyclase; the results also
      provide the first indication of the spatial organization of signaling pathways
      that regulate K(ATP) channel activity.

PMID- 15499026
TI  - Vanilloid receptor TRPV1, sensory C-fibers, and vascular autoregulation: a novel
      mechanism involved in myogenic constriction.
AB  - Myogenic constriction describes the innate ability of resistance arteries to
      constrict in response to elevations in intraluminal pressure and is a fundamental
      determinant of peripheral resistance and, hence, organ perfusion and systemic
      blood pressure. However, the receptor/cell-type that senses changes in pressure
      on the blood vessel wall and the pathway that couples this to constriction of
      vascular smooth muscle remain unclear. In this study, we show that elevation of
      intraluminal transmural pressure of mesenteric small arteries in vitro results in
      a myogenic response that is profoundly suppressed following ablation of sensory C
      fiber activity (using in vitro capsaicin desensitization resulted in 72.8+/-10.3%
      inhibition, n=8; P<0.05). Activation of C-fiber nerve endings by pressure was
      attributable to stimulation of neuronal vanilloid receptor, TRPV1, because
      blockers of this channel, capsazepine (71.9+/-11.1% inhibition, n=9; P<0.001) and
      ruthenium red (46.1+/-11.7% inhibition, n=4; P<0.05), suppressed the myogenic
      constriction. In addition, this C-fiber dependency is likely related to
      neuropeptide substance P release and activity because blockade of tachykinin NK1
      receptors (66.3+/-13.7% inhibition, n=6; P<0.001), and not NK2 receptors (n=4,
      NS), almost abolished the myogenic response. Previous studies support a role for
      20-hydroxyeicosatetraenoic acid (20-HETE) in myogenic constriction responses;
      herein, we show that 20-HETE-induced constriction of mesenteric resistance
      arteries is blocked by capsazepine. Together, these results suggest that
      elevation of intraluminal pressure is associated with generation of 20-HETE that,
      in turn, activates TRPV1 on C-fiber nerve endings resulting in depolarization of
      nerves and consequent vasoactive neuropeptide release. These findings identify a
      novel mechanism contributing to Bayliss' myogenic constriction and highlights an
      alternative pathway that may be targeted in the therapeutics of vascular disease,
      such as hypertension, where enhanced myogenic constriction plays a role in the
      pathogenesis.

PMID- 15499027
TI  - Angiotensin II impairs neurovascular coupling in neocortex through NADPH oxidase
      derived radicals.
AB  - Angiotensin II (Ang II) exerts detrimental effects on cerebral circulation, the
      mechanisms of which have not been elucidated. In particular, Ang II impairs the
      increase in cerebral blood flow (CBF) produced by neural activity, a critical
      mechanism that matches substrate delivery with energy demands in brain. We
      investigated whether Ang II exerts its deleterious actions by activating Ang II
      type 1 (AT1) receptors on cerebral blood vessels and producing reactive oxygen
      species (ROS) through NADPH oxidase. Somatosensory cortex CBF was monitored in
      anesthetized mice by laser-Doppler flowmetry. Ang II (0.25 microg/kg per minute
      IV) attenuated the CBF increase produced by mechanical stimulation of the
      vibrissae. The effect was blocked by the AT1 antagonist losartan and by ROS
      scavenger superoxide dismutase or tiron and was not observed in mice lacking the
      gp91phox subunit of NADPH oxidase or in wild-type mice treated with the NADPH
      oxidase peptide inhibitor gp91ds-tat. Ang II increased ROS production in cerebral
      microvessels, an effect blocked by the ROS scavenger Mn(III)tetrakis (4-benzoic
      acid) porphyrin and by the NADPH oxidase assembly inhibitor apocynin. Ang II did
      not increase ROS production in gp91-null mice. Double-label immunoelectron
      microscopy demonstrated that AT1 and gp91phox immunoreactivities were present in
      endothelium and adventitia of neocortical arterioles. Collectively, these
      findings suggest that Ang II impairs functional hyperemia by activating AT1
      receptors and inducing ROS production via a gp91phox containing NADPH oxidase.
      The data provide the mechanistic basis for the cerebrovascular dysregulation
      induced by Ang II and suggest novel therapeutic strategies to counteract the
      effects of hypertension on the brain.

PMID- 15499028
TI  - Chronic treatment with allopurinol boosts survival and cardiac contractility in
      murine postischemic cardiomyopathy.
AB  - Oxidative stress is a hallmark of systemic illnesses, including heart failure.
      Nevertheless, the overall importance of radical production in the heart remains
      conjectural; is it merely a marker of illness, or can intervention alter the
      progression of disease? This question was addressed by blocking xanthine oxidase
      (XO), a superoxide-generating enzyme that is upregulated in animal models of
      heart failure. In a randomized prospective trial design, we administered the XO
      inhibitor allopurinol orally to mice that had undergone massive myocardial
      infarction (MI). Cardiac XO activity was elevated in untreated mice after MI;
      allopurinol suppressed the XO activity to levels comparable to those in sham
      operated mice. Eighty-one percent of untreated mice died of advanced heart
      failure over 2 to 4 weeks of follow-up. Survival doubled in the allopurinol
      treated mice, whereas cardiac contractile function (both in vivo and in isolated
      muscle) was markedly improved. Response to isoproterenol was restored to near
      normal levels in the allopurinol group but was attenuated in untreated mice.
      Oxidative modifications to proteins were prevented in the allopurinol-treated
      mice. Our findings indicate that targeted blockade of just one source of
      oxidants, XO, impacts dramatically on the progression of postischemic
      cardiomyopathy in mice and prevents oxidative protein modifications.

PMID- 15499030
TI  - Effective prophylaxis for deep vein thrombosis after stroke: low-dose
      anticoagulation rather than stockings alone: for.

PMID- 15499029
TI  - Modulation of cardiac gap junction expression and arrhythmic susceptibility.
AB  - Connexin43 (Cx43), the predominant ventricular gap junction protein, is critical
      for maintaining normal cardiac electrical conduction, and its absence in the
      mouse heart results in sudden arrhythmic death. The mechanisms linking reduced
      Cx43 abundance in the heart and inducibility of malignant ventricular arrhythmias
      have yet to be established. In this report, we investigate arrhythmic
      susceptibility in a murine model genetically engineered to express progressively
      decreasing levels of Cx43. Progressively older cardiac-restricted Cx43
      conditional knockout (CKO) mice were selectively bred to produce a heart-specific
      Cx43-deficient subline ("O-CKO" mice) in which the loss of Cx43 in the heart
      occurs more gradually. O-CKO mice lived significantly longer than the initial
      series of CKO mice but still died suddenly and prematurely. At 25 days of age,
      cardiac Cx43 protein levels decreased to 59% of control values (P<0.01), but
      conduction velocity was not significantly decreased and no O-CKO mice were
      inducible into sustained ventricular tachyarrhythmias. By 45 days of age, cardiac
      Cx43 abundance had decreased in a heterogeneous fashion to 18% of control levels,
      conduction velocity had slowed to half of that observed in control hearts, and
      80% of O-CKO mice were inducible into lethal tachyarrhythmias. Enhanced
      susceptibility to induced arrhythmias was not associated with altered invasive
      hemodynamic measurements or changes in ventricular effective refractory period.
      Thus, moderately severe reductions in Cx43 abundance are associated with slowing
      of impulse propagation and a dramatic increase in the susceptibility to inducible
      ventricular arrhythmias.

PMID- 15499033
TI  - High incidence of neuroendocrine dysfunction in long-term survivors of aneurysmal
      subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: To investigate the incidence, pattern, and magnitude of
      neuroendocrine changes in long-term survivors of aneurysmal subarachnoid
      hemorrhage (SAH). METHODS: Thirty patients (16 women) with a mean age of 50+/-13
      years underwent endocrine assessment between 12 and 24 months after aneurysmal
      SAH. SAH severity was graded clinically by the Hunt & Hess scale (median, II) and
      radiologically by the Fisher classification (median, II). Patients underwent
      measurement of basal hormone levels and dynamic assessment by the low-dose (1
      microg) corticotropin stimulation test. Functional outcome was examined
      concurrently with endocrine testing by the modified Rankin Scale and the Barthel
      Index. RESULTS: Of the 30 patients tested, 14 patients (47%) showed isolated or
      combined endocrine abnormalities. These included low insulin-like growth factor 1
      levels compatible with growth hormone deficiency in 37%, hypogonadism in 13%, and
      cortisol hyporesponsiveness to the low-dose corticotropin stimulation test in
      10%; thyroid dysfunction in the form of subclinical hypothyroidism was observed
      in 7% of patients. Median modified Rankin Scale and Barthel Index at the time of
      endocrine testing were 1 and 100, respectively. There was no correlation between
      the presence of endocrine dysfunction and SAH severity indices or functional
      outcome scores. CONCLUSIONS: Long-term survivors of aneurysmal SAH frequently
      exhibit endocrine changes, with growth hormone and gonadal deficiencies
      predominating. Thus, screening of pituitary function is recommended in patients
      surviving SAH. The relationship between late hormonal alterations and functional
      outcome in patients with SAH warrants further study.

PMID- 15499034
TI  - Is perimesencephalic nonaneurysmal hemorrhage of venous origin?

PMID- 15499036
TI  - Extent and distribution of white matter hyperintensities in stroke patients: the
      Sydney Stroke Study.
AB  - BACKGROUND AND PURPOSE: White matter hyperintensities (WMHs) on T2-weighted MRI
      are common in stroke patients and healthy elderly individuals. The detailed
      anatomical distribution of these lesions in stroke patients has not been
      examined. METHODS: A total of 112 stroke or transient ischemic attack patients
      and 87 matched control subjects from the Sydney Stroke Study underwent MRI scans
      that included a T2-weighted fluid-attenuated inversion recovery (FLAIR) sequence.
      WMHs were delineated from each FLAIR MRI by an automated method. Region of
      interest and voxel-wise statistical parametric mapping approaches were applied to
      examine the volume, distribution, and severity of WMHs of the patient and control
      groups, and subgroups with large or lacunar infarcts. RESULTS: Stroke subjects
      had significantly more WMHs than controls in all brain regions except the
      occipital lobe and in all arterial territories except the anterior callosal and
      anterior medial lenticulostriate. In the frontotemporal regions, average WMH
      volumes in patients were >3.5x those in controls. The total number of discrete
      WMHs was not different in the 2 groups, but stroke patients had more large (>20
      mm) and high-intensity lesions. Subjects with lacunar infarcts had more WMHs than
      those with large infarcts, who, in turn, had more WMHs than control subjects.
      Lacunar infarction subjects had more WMHs than subjects with large thromboembolic
      or cardioembolic strokes. Those with anterior arterial territory infarction had
      more WMHs in the frontal regions. Subjects with single or multiple lacunes did
      not differ in volumes of WMHs. CONCLUSIONS: Stroke patients have significantly
      more WMHs in nearly every brain region than healthy controls. Those with lacunar
      infarcts are particularly affected. WMHs represent a significant proportion of
      the ischemic lesion burden in stroke and transient ischemic attack patients.

PMID- 15499037
TI  - Vitamin D, shedding light on the development of disease in peripheral arteries.
AB  - Vitamin D is generally associated with calcium metabolism, especially in the
      context of uptake in the intestine and the formation and maintenance of bone.
      However, vitamin D influences a wide range of metabolic systems through both
      genomic and nongenomic pathways that have an impact on the properties of
      peripheral arteries. The genomic effects have wide importance for angiogenesis,
      elastogenesis, and immunomodulation; the nongenomic effects have mainly been
      observed in the presence of hypertension. Although some vitamin D is essential
      for cardiovascular health, excess may have detrimental effects, particularly on
      elastogenesis and inflammation of the arterial wall. Vitamin D is likely to have
      a role in the paradoxical association between arterial calcification and
      osteoporosis. This review explores the relationship between vitamin D and a range
      of physiological and pathological processes relevant to peripheral arteries.

PMID- 15499038
TI  - Oral flavonoid supplementation attenuates atherosclerosis development in
      apolipoprotein E-deficient mice.
AB  - OBJECTIVE: Caffeic acid phenethyl ester (CAPE), a natural flavonoid, specifically
      blocks activation of nuclear factor-kappaB (NF-kappaB). We examined the effects
      of oral CAPE supplementation on atherogenesis in apolipoprotein E-deficient (apoE
      /-) mice. METHODS AND RESULTS: Ten-week-old male apoE-/- mice were supplemented
      orally with CAPE (30 mg/kg body weight) for 12 weeks. At the end of
      administration, atherosclerosis progression, NF-kappaB activity, gene expression
      profiling by microarray analysis, and oxidative stress were studied. Treatment of
      apoE-/- mice with CAPE significantly reduced aortic atherosclerosis, NF-kappaB
      activity, and expression of NF-kappaB-related genes in the aorta. Moreover,
      expression of other gene clusters such as basic transcription factors, growth
      factors, cytokines, cell adhesion proteins, and extracellular matrix were also
      significantly reduced by treatment with CAPE. Plasma isoprostane level in apoE-/-
      mice was also significantly reduced by CAPE. CONCLUSIONS: In apoE-/- mice, oral
      CAPE supplementation attenuates the atherosclerotic process. This may be
      attributable to direct inhibition of NF-kappaB in the lesion and reduction of
      systemic oxidative stress. In apoE-/- mice, oral caffeic acid phenethyl ester
      (CAPE) supplementation attenuates the atherosclerotic process and reduces NF
      kappaB activity and expression of NF-kappaB-related genes in the aorta. This may
      be attributable to direct inhibition of NF-kappaB in the lesion and reduction of
      systemic oxidative stress.

PMID- 15499040
TI  - Uterine spiral artery remodeling involves endothelial apoptosis induced by
      extravillous trophoblasts through Fas/FasL interactions.
AB  - OBJECTIVE: Invasion of uterine spiral arteries by extravillous trophoblasts in
      the first trimester of pregnancy results in loss of endothelial and
      musculoelastic layers. This remodeling is crucial for an adequate blood supply to
      the fetus with a failure to remodel implicated in the etiology of the
      hypertensive disorder preeclampsia. The mechanism by which trophoblasts induce
      this key process is unknown. This study gives the first insights into the
      potential mechanisms involved. METHODS AND RESULTS: Spiral arteries were
      dissected from nonplacental bed biopsies obtained at Caesarean section, and a
      novel model was used to mimic in vivo events. Arteries were cultured with
      trophoblasts in the lumen, and apoptotic changes in the endothelial layer were
      detected after 20 hours, leading to loss of endothelium by 96 hours. In vitro,
      coculture experiments showed that trophoblasts stimulated apoptosis of primary
      decidual endothelial cells and an endothelial cell line. This was blocked by
      caspase inhibition and NOK2, a FasL blocking antibody. NOK2 also abrogated
      trophoblast-induced endothelial apoptosis in the vessel model. CONCLUSIONS:
      Extravillous trophoblast induction of endothelial apoptosis is a possible
      mechanism by which the endothelium is removed, and vascular remodeling may occur
      in uterine spiral arteries. Fas/FasL interactions have an important role in
      trophoblast-induced endothelial apoptosis.

PMID- 15499039
TI  - Reduced macrophage apoptosis is associated with accelerated atherosclerosis in
      low-density lipoprotein receptor-null mice.
AB  - OBJECTIVE: The majority of apoptotic cells in atherosclerotic lesions are
      macrophages. However, the pathogenic role of macrophage apoptosis in the
      development of atherosclerosis remains unclear. Elevated expression of Bax, one
      of the pivotal proapoptotic proteins of the Bcl-2 family, has been found in human
      atherosclerotic plaques. Activation of Bax also occurs in free cholesterol-loaded
      and oxysterol-treated mouse macrophages. In this study, we examined the effect of
      Bax deficiency in bone marrow-derived leukocytes on the development of
      atherosclerosis in low-density lipoprotein receptor-null (LDLR-/-) mice. METHODS
      AND RESULTS: Fourteen 8-week-old male LDLR-/- mice were lethally irradiated and
      reconstituted with either wild-type (WT) C57BL6 or Bax-null (Bax-/-) bone marrow.
      Three weeks later, the mice were challenged with a Western diet for 10 weeks. No
      differences were found in the plasma cholesterol level between the WT and Bax-/-
      group. However, quantitation of cross sections from proximal aorta revealed a
      49.2% increase (P=0.0259) in the mean lesion area of the Bax-/- group compared
      with the WT group. A 53% decrease in apoptotic macrophages in the Bax-/- group
      was found by TUNEL staining (P<0.05). CONCLUSIONS: The reduction of apoptotic
      activity in macrophages stimulates atherosclerosis in LDLR-/- mice, which is
      consistent with the hypothesis that macrophage apoptosis suppresses the
      development of atherosclerosis.

PMID- 15499041
TI  - Angiotensin II-induced protein kinase D activation is regulated by protein kinase
      Cdelta and mediated via the angiotensin II type 1 receptor in vascular smooth
      muscle cells.
AB  - OBJECTIVE: Angiotensin II (Ang II), through its specific signaling cascades,
      exerts multiple effects on vascular smooth muscle cells (SMCs). It has been shown
      that Ang II stimulates activation of protein kinase D (PKD), a member of a new
      class of serine-threonine kinases. However, little is known regarding the
      upstream cascade of the intracellular signaling that leads to PKD activation. In
      the present study, we investigated upstream molecules that mediate Ang II-induced
      PKD activation in SMCs. METHODS AND RESULTS: Protein kinase C (PKC) inhibitors
      completely block Ang II-induced PKD activation, and pretreatment with phorbol
      12,13-dibutyrate downregulates Ang II-induced PKD activation, indicating that
      classical or novel isoforms of PKC mediate Ang II-induced PKD activation.
      Furthermore, the finding that rottlerin, a PKCdelta-specific inhibitor, blocks
      PKD activation suggests that PKCdelta, a member of novel PKCs, mediates Ang II
      induced PKD activation. By using dominant-negative approaches, our results
      demonstrate that expression of the dominant-negative PKCdelta, but neither the
      dominant-negative form of PKCepsilon nor PKCzeta, inhibits PKD activation. These
      results further substantiate the finding that Ang II-induced PKD activation is
      mediated by PKCdelta. Moreover, using selective Ang II receptor antagonists, our
      data show that the Ang II type 1 (AT1) receptor but not the AT2 mediates Ang II
      stimulated PKD activation. CONCLUSIONS: This study reveals for the first time
      that Ang II-induced PKD activation is mediated via AT1 and regulated by PKCdelta
      in living cells. These data may provide new insights into molecular mechanisms
      involved in Ang II-induced physiological and pathological events.

PMID- 15499042
TI  - Bilirubin from heme oxygenase-1 attenuates vascular endothelial activation and
      dysfunction.
AB  - OBJECTIVE: Heme oxygenase-1 (HO-1), the rate-limiting enzyme of heme degradation,
      has recently been considered to have protective roles against various
      pathophysiological conditions. Since we demonstrated that HO-1 overexpression
      inhibits atherosclerotic formation in animal models, we examined the effect of HO
      modulation on proinflammatory cytokine production, endothelial NO synthase (eNOS)
      expression, and endothelium-dependent vascular relaxation responses. METHODS AND
      RESULTS: After HO-1 induction by heme arginate (HA), vascular endothelial cell
      cultures were exposed to oxidized low-density lipoprotein (oxLDL) or tumor
      necrosis factor-alpha (TNF-alpha). HA pretreatment significantly attenuated the
      production of vascular cell adhesion molecule-1, monocyte chemotactic protein-1,
      and macrophage colony-stimulating factor, suggesting that HO-1 induction
      attenuates proinflammatory responses. In addition, HO-1 overexpression also
      alleviated endothelial dysfunction as judged by restoration of attenuated eNOS
      expression after exposure to oxLDL and TNF-alpha. Importantly, impaired
      endothelium-dependent vascular relaxation responses in thoracic aortic rings from
      high-fat-fed LDL receptor knockout mice were also improved. These effects were
      observed by treatment with bilirubin not by carbon monoxide. CONCLUSIONS: These
      results suggest that the antiatherogenic properties of HO-1 may be mediated
      predominantly through the action of bilirubin by inhibition of vascular
      endothelial activation and dysfunction in response to proinflammatory stresses.

PMID- 15499043
TI  - Association between elevated liver enzymes and C-reactive protein: possible
      hepatic contribution to systemic inflammation in the metabolic syndrome.
AB  - OBJECTIVE: The objective of this study was to test whether the frequent
      association between liver enzyme elevations and various components of the
      metabolic syndrome is associated with higher C-reactive protein (CRP) levels.
      METHODS AND RESULTS: Alanine aminotransferase (ALT), alkaline phosphatase (Alk
      P), and high-sensitivity CRP were measured in 1740 subjects. Adjusted geometric
      mean CRP was calculated for subjects with normal and elevated ALT and for
      subjects with normal and elevated Alk-P, adjusting for age, sex, smoking,
      physical activity, body mass index, fasting glucose, triglycerides, the presence
      of hypertension and low HDL cholesterol, and use of aspirin or hormone
      replacement therapy. Adjusted CRP levels were higher in subjects with elevated
      ALT (2.21 versus 1.94 mg/L, P=0.028) or elevated Alk-P (2.58 versus 1.66 mg/L,
      P<0.0001). Logistic regression showed that compared with subjects with normal
      liver function tests, the adjusted odds for high-risk CRP (>3 mg/L) were
      significantly higher in subjects with elevated ALT (OR, 1.5; 95% CI, 1.2 to 1.9,
      P=0.002) or elevated Alk-P (OR, 2.1; 95% CI, 1.7 to 2.6, P<0.0001). CONCLUSIONS:
      Elevations of liver enzymes are associated with higher CRP concentrations.
      Hepatic inflammation secondary to liver steatosis is a potential contributor to
      the low-grade inflammation associated with the metabolic syndrome.

PMID- 15499044
TI  - ACAT1 deficiency disrupts cholesterol efflux and alters cellular morphology in
      macrophages.
AB  - OBJECTIVE: Acyl-coenzyme A: cholesterol acyltransferase (ACAT) converts
      intracellular free cholesterol (FC) into cholesteryl esters (CE) for storage in
      lipid droplets. Recent studies in our laboratory have shown that the deletion of
      the macrophage ACAT1 gene results in apoptosis and increased atherosclerotic
      lesion area in the aortas of hyperlipidemic mice. The objective of the current
      study was to elucidate the mechanism of the increased atherosclerosis. METHODS
      AND RESULTS: CE storage and FC efflux were studied in ACAT1(-/-) peritoneal
      macrophages that were treated with acetylated low-density lipoprotein (acLDL).
      Our results show that efflux of cellular cholesterol was reduced by 25% in ACAT1
      deficient cells compared with wild-type controls. This decrease occurred despite
      the upregulated expression of ABCA1, an important mediator of cholesterol efflux.
      In contrast, ACAT1 deficiency increased efflux of the cholesterol derived from
      acLDL by 32%. ACAT1-deficient macrophages also showed a 26% increase in the
      accumulation of FC derived from acLDL, which was associated with a 75% increase
      in the number of intracellular vesicles. CONCLUSIONS: Together, these data show
      that macrophage ACAT1 influences the efflux of both cellular and lipoprotein
      derived cholesterol and propose a pathway for the pro-atherogenic transformation
      of ACAT1(-/-) macrophages.

PMID- 15499045
TI  - Association of lipoprotein-associated phospholipase A2 mass and activity with
      calcified coronary plaque in young adults: the CARDIA study.
AB  - OBJECTIVE: To examine the association of lipoprotein-associated phospholipase A2
      (Lp-PLA2) mass and activity with calcified coronary plaque in young adults.
      METHODS AND RESULTS: Nested case-control study among CARDIA participants at the
      year 15 examination (2000 to 2001, 33 to 45 years old). Cases (n=266) were those
      with and controls (n=266) those without evidence of calcified coronary plaque by
      computed tomography matched 1:1 on sex and race. Lp-PLA2 mass and activity were
      significantly higher in cases (296+/-101 ng/mL and 36.4+/-12.3 nmol/mL per
      minute) than in controls (267+/-80 ng/mL and 32.9+/-11.8 nmol/mL per minute). In
      age-adjusted conditional logistic regression, the odds ratio (OR) of calcified
      coronary plaque per 1 standard deviation (SD) increment was 1.40 (95% CI, 1.17 to
      1.67) and 1.39 (95% CI, 1.14 to 1.70) for Lp-PLA2 mass and activity,
      respectively. After adjusting for multiple covariates including low-density
      lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C),
      triglycerides, and C-reactive protein, a statistically significant association
      remained for Lp-PLA2 mass (OR, 1.28; 95% CI, 1.03 to 1.60) but not for activity
      (OR, 1.09; 95% CI, 0.84 to 1.42). No evidence was found for interaction between
      Lp-PLA2 mass or activity with LDL-C as predictors of calcified coronary plaque.
      CONCLUSIONS: An independent association of Lp-PLA2 mass with calcified coronary
      plaque existed in young adults. Therefore, Lp-PLA2 mass may be a useful marker of
      subclinical cardiovascular risk.

PMID- 15499046
TI  - Acyl-coenzymeA (CoA):cholesterol acyltransferase inhibition in rat and human
      aortic smooth muscle cells is nontoxic and retards foam cell formation.
AB  - OBJECTIVE: Studies in vitro and in vivo of macrophage foam cells have shown
      evidence of cytotoxicity after acyl-CoA:cholesterol acyltransferase (ACAT)
      inhibition. Foam cells of smooth muscle origin are also found in human and animal
      atherosclerotic lesions. METHODS AND RESULTS: To study whether cytotoxicity from
      ACAT inhibition is independent of cell type, we first established a protocol to
      conveniently induce aortic smooth muscle foam cell formation using cholesterol
      cyclodextrin complexes (CCC). Rat aortic smooth muscle cells (ASMCs) treated for
      48 hours with CCC (20 microg/mL) became foam cells by morphological (oil-red-O
      staining) and biochemical (approximately 1200% and approximately 180% increase in
      cellular esterified and free cholesterol, respectively) criteria. ACAT activity
      increased 500% (P<0.01 versus untreated). Similar results were obtained in human
      ASMC, but ACAT activity increased to an even greater extent (3200%; P<0.01 versus
      untreated). Western blots indicated that CCC treatment increased human (to 380+/
      20% of untreated, P<0.001), but not rat, ACAT protein expression. ACAT inhibition
      by Fujirebio compound F1394 suppressed CCC-induced foam cell formation in rat and
      human ASMC, but, notably, did not induce significant cytotoxicity. CONCLUSIONS:
      ASMC might be more resistant to FC-induced adverse effects than are macrophages.

PMID- 15499047
TI  - The future of community children's nursing.

PMID- 15499048
TI  - Long term cognitive development in children with prolonged crying.
AB  - BACKGROUND: Long term studies of cognitive development and colic have not
      differentiated between typical colic and prolonged crying. OBJECTIVE: To evaluate
      whether colic and excessive crying that persists beyond 3 months is associated
      with adverse cognitive development. DESIGN: Prospective cohort study. A sample of
      561 women was enrolled in the second trimester of pregnancy. Colic and prolonged
      crying were based on crying behaviour assessed at 6 and 13 weeks. Children's
      intelligence, motor abilities, and behaviour were measured at 5 years (n = 327).
      Known risk factors for cognitive impairment were ascertained prenatally, after
      birth, at 6 and 13 weeks, at 6, 9, and 13 months, and at 5 years of age. RESULTS:
      Children with prolonged crying (but not those with colic only) had an adjusted
      mean IQ that was 9 points lower than the control group. Their performance and
      verbal IQ scores were 9.2 and 6.7 points lower than the control group,
      respectively. The prolonged crying group also had significantly poorer fine motor
      abilities compared with the control group. Colic had no effect on cognitive
      development. CONCLUSIONS: Excessive, uncontrolled crying that persists beyond 3
      months of age in infants without other signs of neurological damage may be a
      marker for cognitive deficits during childhood. Such infants need to be examined
      and followed up more intensively.

PMID- 15499049
TI  - Caesarean section and gastrointestinal symptoms, atopic dermatitis, and
      sensitisation during the first year of life.
AB  - AIMS: To investigate the effect of caesarean section on gastrointestinal
      symptoms, atopic dermatitis, and sensitisation to nutritional allergens in
      infants. METHODS: A total of 865 healthy full term neonates with parental history
      of allergy participating in the prospective German Infant Nutritional
      Intervention Program (GINI) were exclusively breast fed during the first four
      months of life and had a one year follow up. Data were obtained by follow up
      visits at age 1, 4, 8, and 12 months, weekly diaries for the first six months,
      and measurement of total and specific IgE at birth and 12 months. RESULTS:
      Infants born by caesarean section (147/865, 17%) had a greater risk of diarrhoea
      (OR(adj) 1.46, 95% CI 1.022 to 2.10) and sensitisation to food allergens, both in
      adjusted (OR(adj) 2.06, 95% CI 1.123 to 3.80) and stratified analyses (by cord
      blood IgE). Caesarean delivery was not associated with colicky pain and atopic
      dermatitis. CONCLUSION: Caesarean delivery might be a risk factor for diarrhoea
      and sensitisation in infants with family history of allergy. Further research in
      this area seems warranted as choosing caesarean section becomes increasingly
      popular.

PMID- 15499050
TI  - Survey of administration of medicines to pupils in primary schools within the
      London area.
AB  - OBJECTIVE: To examine the policy, administration, and supervision of medicine
      administration in primary schools within the Greater London area (GLA). DESIGN: A
      prospective survey using postal questionnaires sent to 172 randomly selected
      primary schools within the GLA. PARTICIPANTS: Head teachers of primary schools.
      RESULTS: Some 65% of head teachers replied. Less than 50% of responding head
      teachers had actually read the national guidelines Supporting Pupils with Medical
      Needs and only 30% of respondents were aware of other members of staff who had
      read the document. A total of 95% of respondents followed a policy/procedure in
      caring for the medical needs of pupils. Over 80% of respondents had staff
      handling the pupils' medical needs, staff handling access to stored medicines,
      and prior arrangements for staff training. However, it is worrying that a quarter
      of the schools did not keep a written record of medicines given to children in
      schools. The majority of staff with responsibility for medicine administration in
      schools are support staff. The most encouraging findings were that for the
      majority of schools with children using the EpiPen and rectal diazepam, there
      were trained staff to administer these medicines. CONCLUSIONS: The majority of
      schools had a policy in place to deal with medicine administration, although
      further work should be conducted to analyse the content of such policies. It is
      very important that training is directed at staff responsible for medicine
      administration and not just at teachers. Most schools were willing to administer
      rectal diazepam and EpiPen treatment in an emergency.

PMID- 15499051
TI  - Burden of influenza in healthy children and their households.
AB  - OBJECTIVE: A prospective, multicentre study was conducted to evaluate the burden
      of laboratory confirmed influenza in healthy children and their household
      contacts. METHODS: The patients were enrolled in four emergency departments (EDs)
      and by five primary care paediatricians (PCPs) in different Italian
      municipalities 2 days a week between November 1, 2001 and April 30, 2002. The
      study involved 3771 children less than 14 years of age with no chronic medical
      conditions who presented with a respiratory tract infection in EDs or PCP
      outpatient clinics during the study period. Nasopharyngeal swabs were collected
      for the isolation of influenza viruses and RNA detection. Information was also
      collected concerning respiratory illnesses and related morbidities among the
      study children and their household contacts. RESULTS: Influenza virus was
      demonstrated in 352 cases (9.3%). In comparison with the influenza negative
      children, those who were influenza positive had an older mean age, were more
      often attending day care centres or schools, more frequently experienced fever
      and croup, received more antipyretics, and had a longer duration of fever and
      school absence. Furthermore, their parents and siblings had more respiratory
      illnesses, received more antipyretics and antibiotics, needed more medical
      visits, missed more work or school days, and needed help at home to care for the
      ill children for a longer period of time. CONCLUSIONS: Influenza has a
      significant clinical and socioeconomic impact on healthy children and their
      families. Prevention strategies should also focus on healthy children regardless
      of their age because of their role in disease transmission.

PMID- 15499052
TI  - The siblings of childhood cancer patients need early support: a follow up study
      over the first year.
AB  - BACKGROUND AND METHODS: In a 1 year follow up study, we assessed the life
      situation of 33 siblings of childhood cancer patients and 357 healthy controls.
      The hypothesis was that siblings have more behavioural and health related
      problems just after the cancer diagnosis. Validated assessment methods were used.
      RESULTS: Siblings below school age tended to have conduct problems, psychosomatic
      problems, and a mixed group of other behavioural problems, when assessed 3 months
      after the cancer diagnosis. These symptoms became less evident during follow up.
      Among the school aged siblings, however, conduct problems, learning problems,
      psychosomatic problems, impulsive-hyperactive symptoms, and other behavioural
      symptoms remained unchanged during follow up. In their self assessments, the
      school aged siblings showed both state and trait anxiety more often than controls
      at the first assessment, but later these symptoms settled to the same level as
      the controls. The overall Children's Depression Inventory (CDI) depression scores
      did not show differences between the study groups. CONCLUSIONS: The ratings of
      the parents were in keeping with the self assessment of the school aged siblings
      only in a few aspects; the emphasis of findings can be changed when proxies are
      used. The siblings have symptoms and adverse feelings which probably could be
      relieved by targeted, early information about the illness, and possibly by group
      discussions or activities, soon after the cancer diagnosis. In order to obtain
      necessary support for the siblings with educational problems, school personnel
      need to be informed about the sibling distress.

PMID- 15499053
TI  - Cancers and immune related diseases associated with Down's syndrome: a record
      linkage study.
AB  - OBJECTIVE: To determine the risk of cancers and selected immune related diseases
      in people with Down's syndrome, relative to risk in other people. DESIGN: Cohort
      analysis of a linked dataset of abstracts of hospital and death records; results
      expressed as the ratios of rates of disease in people with and without Down's
      syndrome. SETTING: The former Oxford health region, England, 1963-1999. SUBJECTS:
      Cohort of 1453 people with Down's syndrome and cohort of 460,000 people with
      other conditions for comparison. MAIN OUTCOMES: As expected, the rate ratio for
      leukaemia was substantially elevated in people with Down's syndrome: it was 19
      fold higher (95% confidence intervals 10.4 to 31.5) than the rate in the
      comparison cohort. For other cancers combined, excluding leukaemia, the rate
      ratio was not significantly elevated (1.2; 0.6 to 2.2). The risk of testicular
      cancer was increased (12.0; 2.5 to 35.6), although this was based on only three
      cases in the cohort of subjects with Down's syndrome. Significantly elevated
      risks were found for coeliac disease (4.7; 1.3 to 12.2), acquired hypothyroidism
      (9.4; 3.4, 20.5), other thyroid disorders, and type 1 diabetes mellitus (2.8; 1.0
      to 6.1). A decreased risk was found for asthma (0.4; 0.2 to 0.6). CONCLUSIONS:
      Our data add to the body of information on the risks of co-morbidity in people
      with Down's syndrome. The finding on asthma needs to be confirmed or refuted by
      other studies.

PMID- 15499054
TI  - Are inequalities in height narrowing? Comparing effects of social class on height
      in two generations.
AB  - OBJECTIVE: To determine whether social inequalities in height change across
      generations. METHODS: The target population was from the 1958 British birth
      cohort, all born 3rd-9th March 1958, followed to 1991, and the offspring of one
      third of this population. Main outcomes were height measured at 7, 11, 16, and 33
      years (cohort members) and once at 4-18 years (offspring). Multilevel models
      applied to associations of social class of origin with (a) child-to-adult growth
      trajectory (cohort members), (b) height (offspring), and (c) generational height
      increment. RESULTS: Height inequalities were observed among cohort members, with
      differences >2.0 cm at all ages between classes I and II, and IV and V. By
      adulthood, the difference in mean height had declined significantly in boys and
      slightly in girls. A secular trend was seen between the two generations. While
      male offspring had a similar mean height to their fathers in classes I and II,
      boys in classes IV and V gained 2.1 cm (p<0.001). Height gains of female
      offspring were evident in all classes, with a greater gain in classes IV and V
      (non-significant). The social class effect on height was weaker among offspring,
      with a difference between classes I and II, and IV and V of less than 1 cm.
      CONCLUSIONS: Social inequalities in height observed among the cohort weakened
      substantially in the next generation due to a greater height gain among offspring
      from manual classes. Inequalities in childhood height have narrowed between the
      two generations in this study.

PMID- 15499055
TI  - Growth hormone (GH) provocation tests and the response to GH treatment in GH
      deficiency.
AB  - OBJECTIVE: To identify factors, particularly the growth hormone (GH) provocation
      test result, affecting growth response to GH treatment in children with GH
      deficiency (GHD). SUBJECTS: A total of 337 prepubertal GHD patients aged <10
      years from the UK Pharmacia KIGS database (GH response to provocation test <20
      mU/l). OUTCOME MEASURE: Annual change in height standard deviation score (SDS)
      (revised UK reference) in the first and second years of treatment. RESULTS:
      Height increased by 0.74 SDS units (SD 0.39) in the first year of treatment and
      0.37 units (SD 0.27) in the second. Adjusting for age, height, weight, midparent
      height, and injection frequency, the strongest predictor of first year growth
      response was the GH provocation test result; halving the result predicted an
      extra height increment of 0.09 units (p<0.0001). It predicted the second year
      response less well (p<0.0002) and after adjusting for the first year response was
      not predictive at all. CONCLUSIONS: Among patients referred for possible GHD, the
      GH provocation test, though not a gold standard for diagnosis, is a valuable
      predictor of growth response in the first year of treatment. A year's treatment
      is recommended for cases with a marginal provocation test result, with the option
      to continue treatment if the response is adequate. The value of unified protocols
      for single or repeated provocation tests needs to be assessed.

PMID- 15499056
TI  - The diagnosis of borderline iron deficiency: results of a therapeutic trial.
AB  - BACKGROUND: Iron deficiency is common in early childhood and has been associated
      with developmental delay. It is not known how reliably markers of iron deficiency
      identify true iron deficiency, defined as a therapeutic response to oral iron.
      METHODS: The subjects were members of the Millennium Baby Study cohort. At age 13
      months a venous blood sample was taken for mean cell volume (MCV), haemoglobin,
      mean cell haemoglobin (MCH), ferritin, and zinc protoporphyrin (ZPP). Children
      with abnormal values were offered treatment with oral iron and dietary
      modification, and re-sampled after 3 months. RESULTS: Samples were obtained for
      462 children. All markers were moderately correlated with each other except
      ferritin. Treatment was offered to 147 (32%) children with at least one abnormal
      value, of whom 126 (86%) were re-sampled. Children with a haemoglobin or an MCH
      below the screening cut off, or with abnormal values for two or more of the
      remaining three measures, showed a large therapeutic response to iron, but
      isolated abnormalities of MCV, ZPP, or ferritin were not consistently associated
      with a response. Of the screened population 13% could be defined as iron
      deficient (abnormal haemoglobin or MCH, or abnormal levels of two or more of the
      remaining three markers), but this was not strongly associated with any dietary,
      demographic, or anthropometric characteristic. CONCLUSIONS: Low total or mean
      cell haemoglobin in isolation is a specific marker of iron deficiency, but other
      markers are only predictive when found in combination with other abnormal values.

PMID- 15499057
TI  - Copies of clinic letters to the family.
AB  - In April 2004 guidelines were introduced advising that letters to the GP should
      be copied to parents of young people. A study was carried out to ascertain the
      views of young people and their parents as to who they felt should receive
      correspondence after an outpatient appointment.

PMID- 15499058
TI  - High tolerance for oral galactose in classical galactosaemia: dietary
      implications.
AB  - AIM: To study the relevance of restricting the exogenous intake of small amounts
      of galactose, such as from fruit and vegetables, in patients with classical
      galactosaemia. METHODS: For a period of six weeks, increasing doses of oral
      galactose to a maximum of 600 mg per day, were added to a very strict galactose
      restricted diet in three adolescent patients homozygous for the Q188R mutation.
      During the study, physical examination, including an extended ophthalmic
      examination, and laboratory studies were performed on a weekly basis. RESULTS: No
      significant change in any of the studied clinical or biochemical parameters was
      observed. CONCLUSIONS: These findings provide further evidence that attempts to
      exclude trace amounts of galactose from the diet are not justified. Once the diet
      is made more liberal, a long term follow up study will be necessary.

PMID- 15499059
TI  - Flies and Helicobacter pylori infection.
AB  - Houseflies have been proposed to be a reservoir and vector for Helicobacter
      pylori. We assessed the effect of insecticide spraying in villages in The Gambia
      on H. pylori infection in young children. Effective control of flies did not
      prevent infection with H. pylori.

PMID- 15499060
TI  - Infant hearing screening: route to informed choice.
AB  - The decision to participate in infant screening often rests with parents. Medical
      ethics require that parental decision is elicited from informed choice. Such a
      decision is influenced by the parental knowledge and attitude towards screening
      and a careful evaluation of these factors is essential in seeking informed
      consent for infant hearing screening.

PMID- 15499061
TI  - Determinants of universal adolescent hepatitis B vaccine uptake.
AB  - The UK is currently considering the introduction of universal hepatitis B
      vaccination. This study of determinants of vaccine uptake among school based
      adolescents shows that living in areas of high deprivation, commonly associated
      with injecting drug risk behaviours, was the most important factor, with
      statistically significant lower odds of receiving three doses. This was less
      pronounced for receipt of two doses. Thus, there are implications for future
      policy; if universal vaccination is approved, a licensed two dose schedule would
      be most appropriate in this setting.

PMID- 15499062
TI  - Causes of apparent life threatening events in infants: a systematic review.
AB  - AIMS: To determine the most likely diagnoses when infants first present with an
      apparent life threatening event (ALTE). METHODS: Medline (1966-2002), Embase
      (1980-2002), and Cinahl (1982-2002) were searched. Primary authors and content
      experts were contacted to identify further studies. Bibliographies from studies,
      reviews, and textbooks were searched. Foreign language studies were translated.
      Articles were included if the ALTE was clearly defined and if the evaluation
      recorded was from the initial contact. Case reports and studies focusing on
      single conditions or non-clinical data were excluded. RESULTS: From an initial
      2912 papers, eight studies involving 643 infants (aged 0-13 months) were
      included. All studies were non-randomised and methodological quality varied. All
      diagnoses were made after evaluation in hospital but investigation protocols
      varied widely. There were 728 diagnoses assigned overall. Some infants had
      multiple diagnoses. The most common diagnoses were gastro-oesophageal reflux (n =
      227), seizure (n = 83), lower respiratory tract infection (n = 58), and "unknown"
      (n = 169). Five deaths were noted in total. CONCLUSIONS: There is a wide range of
      diagnoses reported after evaluation of an ALTE. Differing management protocols
      contributed to variations in the frequency of the diagnoses. The development and
      validation of an evidence based management plan may contribute to the care of
      this common condition.

PMID- 15499063
TI  - Assessment and management of children aged 1-59 months presenting with wheeze,
      fast breathing, and/or lower chest indrawing; results of a multicentre
      descriptive study in Pakistan.
AB  - BACKGROUND AND AIMS: Using current WHO guidelines, children with wheezing are
      being over prescribed antibiotics and bronchodilators are underutilised. To
      improve the WHO case management guidelines, more data is needed about the
      clinical outcome in children with wheezing/pneumonia overlap. METHODOLOGY: In a
      multicentre prospective study, children aged 1-59 months with
      auscultatory/audible wheeze and fast breathing and/or lower chest indrawing were
      screened. Response to up to three cycles of inhaled salbutamol was recorded. The
      responders were enrolled and sent home on inhaled bronchodilators, and followed
      up on days 3 and 5. RESULTS: A total of 1622 children with wheeze were screened
      from May 2001 to April 2002, of which 1004 (61.8%) had WHO defined non-severe and
      618 (38.2%) severe pneumonia. Wheeze was audible in only 595 (36.7%) of children.
      Of 1004 non-severe pneumonia children, 621 (61.8%) responded to up to three
      cycles of bronchodilator. Of 618 severe pneumonia children, only 166 (26.8%)
      responded. Among responders, 93 (14.9%) in the non-severe and 63 (37.9%) children
      in the severe pneumonia group showed subsequent deterioration on follow ups. No
      family history of wheeze, temperature >100 degrees F, and lower chest indrawing
      were identified as predictors of subsequent deterioration. CONCLUSIONS: Two third
      of children with wheeze are not identified by current WHO ARI (acute respiratory
      infections) guidelines. Antibiotics are over prescribed and bronchodilators under
      utilised in children with wheeze. Children with wheeze constitute a special ARI
      group requiring a separate management algorithm. In countries where wheeze is
      common it would be worthwhile to train health workers in use of the stethoscope
      to identify wheeze.

PMID- 15499064
TI  - Decreased cortisol response to insulin induced hypoglycaemia in asthmatics
      treated with inhaled fluticasone propionate.
AB  - AIMS: To assess adrenal function in asthmatic children treated with inhaled
      fluticasone propionate for up to 16 weeks. METHODS: Children with asthma and
      bronchial hyperresponsiveness to inhaled methacholine were treated with inhaled
      fluticasone 250-750 microg/day via Volumatic spacer. The insulin tolerance test
      (ITT) was performed to assess adrenal function. RESULTS: Eighteen asthmatic
      patients (10 boys, 8 girls), aged 7-17 years received inhaled fluticasone therapy
      at a median dose of 477 microg/m2 per day for 5-16 weeks. Adrenal suppression,
      defined as 60 minute serum cortisol less than 500 nmol/l, was found in 9 of 18
      children. Following the ITT, the median basal and 60 minute serum cortisol
      concentrations of the suppressed group were 135.0 and 350.0 nmol/l, respectively;
      the corresponding values for the unsuppressed group were 242.2 and 564.7 nmol/l.
      Repeat ITT in the suppressed group 2-3 months after discontinuation of
      fluticasone revealed that all patients had a 60 minute serum cortisol greater
      than 500 nmol/l. CONCLUSION: After therapy for asthma with inhaled fluticasone at
      approximately 500 microg daily for up to 16 weeks, half the children had evidence
      of adrenal suppression.

PMID- 15499065
TI  - Validity and reliability of acoustic analysis of respiratory sounds in infants.
AB  - OBJECTIVE: To investigate the validity and reliability of computerised acoustic
      analysis in the detection of abnormal respiratory noises in infants. METHODS:
      Blinded, prospective comparison of acoustic analysis with stethoscope
      examination. Validity and reliability of acoustic analysis were assessed by
      calculating the degree of observer agreement using the kappa statistic with 95%
      confidence intervals (CI). RESULTS: 102 infants under 18 months were recruited.
      Convergent validity for agreement between stethoscope examination and acoustic
      analysis was poor for wheeze (kappa = 0.07 (95% CI, -0.13 to 0.26)) and rattles
      (kappa = 0.11 (-0.05 to 0.27)) and fair for crackles (kappa = 0.36 (0.18 to
      0.54)). Both the stethoscope and acoustic analysis distinguished well between
      sounds (discriminant validity). Agreement between observers for the presence of
      wheeze was poor for both stethoscope examination and acoustic analysis. Agreement
      for rattles was moderate for the stethoscope but poor for acoustic analysis.
      Agreement for crackles was moderate using both techniques. Within-observer
      reliability for all sounds using acoustic analysis was moderate to good.
      CONCLUSIONS: The stethoscope is unreliable for assessing respiratory sounds in
      infants. This has important implications for its use as a diagnostic tool for
      lung disorders in infants, and confirms that it cannot be used as a gold
      standard. Because of the unreliability of the stethoscope, the validity of
      acoustic analysis could not be demonstrated, although it could discriminate
      between sounds well and showed good within-observer reliability. For acoustic
      analysis, targeted training and the development of computerised pattern
      recognition systems may improve reliability so that it can be used in clinical
      practice.

PMID- 15499066
TI  - The incidence and mortality for meningococcal disease associated with area
      deprivation: an ecological study of hospital episode statistics.
AB  - AIMS: To determine whether incidence, mortality, and case fatality for
      meningococcal disease (MD) differs by area deprivation, and if this has changed
      over time. METHODS: The population of children aged less than 5 years with MD was
      analysed as quintiles of area deprivation scores over two time periods, 1995-99
      and 1991-94. Annual age standardised rates were calculated and the association
      between incidence, mortality, and area deprivation quintiles assessed using
      Poisson regression and the risk ratios determined. Case fatality was calculated
      from the odds ratio of mortality by area deprivation score for the two time
      periods. RESULTS: There were 10,524 cases of MD and 441 deaths (4.2%). Incidence
      rates were higher for 1995-99 (45.4 per 100,000) compared to 1991-94 (27.4 per
      100,000). Mortality rates remained stable over time, indicating a decline in risk
      of death of around 40%. The incidence rates for the most deprived quintile were
      around twice those for the most affluent quintile, but this gradient declined
      over time. A threefold gradient was seen for mortality rates across the top and
      bottom quintiles, which was constant over time. The odds of mortality did not
      show a linear pattern, with mortality being lowest in the first and highest in
      the second and fifth area deprivation quintiles. CONCLUSIONS: These data show
      that MD incidence and mortality are socially patterned. The determinants of case
      fatality are more complex and require further investigation.

PMID- 15499067
TI  - Nephrolithiasis associated with ceftriaxone therapy: a prospective study in 51
      children.
AB  - BACKGROUND: Ceftriaxone, a third generation cephalosporin, is widely used for
      treating infection during childhood. The kidneys eliminate approximately 33-67%
      of this agent, and the remainder is eliminated via the biliary system.
      Ceftriaxone may bind with calcium ions and form insoluble precipitate leading to
      biliary pseudolithiasis. The aim of this study was to assess whether ceftriaxone
      associated nephrolithiasis develops by the same mechanism, and whether this
      condition is dose related. METHODS: The study involved 51 children with various
      infections. Of these, 24 were hospitalized with severe infection and received 100
      mg/kg/day ceftriaxone divided into two equal intravenous doses. The other 27
      patients received a single daily intramuscular injection of 50 mg/kg/day. Serum
      and urine parameters were evaluated before and after treatment, and abdominal
      ultrasonographic examinations were also carried out before and after treatment.
      RESULTS: Serum urea, creatinine, and calcium levels were normal in all patients
      before and after treatment. Post-treatment ultrasound identified nephrolithiasis
      in four (7.8%) of the 51 subjects. The stones were all of small size (2 mm).
      Comparison of the groups with and without nephrolithiasis revealed no significant
      differences with respect to age, sex distribution, duration of treatment, or
      dose/route of administration of ceftriaxone. The renal stones disappeared
      spontaneously in three of the four cases, but were still present in one patient 7
      months after ceftriaxone treatment. CONCLUSIONS: Conclusions: The study showed
      that children taking a 7 day course of normal or high dose ceftriaxone may
      develop small sized asymptomatic renal stones. The overall incidence of
      nephrolithiasis in this study was 7.8%.

PMID- 15499068
TI  - Living with primary ciliary dyskinesia (PCD).

PMID- 15499069
TI  - Ethnic group differences in overweight and obese children with type 1 diabetes
      mellitus.

PMID- 15499070
TI  - Bloodless treatment of infants with haemolytic disease.

PMID- 15499071
TI  - Ethics; the third dimension.

PMID- 15499072
TI  - Evidence based guideline for post-seizure management.

PMID- 15499073
TI  - Soy formulas and hypothyroidism.

PMID- 15499074
TI  - ESPE/LWPES Consensus Statement on diabetic ketoacidosis in children and
      adolescents (Arch Dis Child 2004;89:188-94).

PMID- 15499075
TI  - Rib periosteal reaction: did you think about chest physical therapy?

PMID- 15499076
TI  - Think laterally!

PMID- 15499077
TI  - Splenectomy in cystic fibrosis patients.

PMID- 15499078
TI  - Characterization of intracellular Ca(2+) stores in gallbladder smooth muscle.
AB  - The existence of functionally distinct intracellular Ca(2+) stores has been
      proposed in some types of smooth muscle. In this study, we sought to examine
      Ca(2+) stores in the gallbladder by measuring intracellular Ca(2+) concentration
      ([Ca(2+)](i)) in fura 2-loaded isolated myocytes, membrane potential in intact
      smooth muscle, and isometric contractions in whole mount preparations. Exposure
      of isolated myocytes to 10 nM CCK caused a transient elevation in [Ca(2+)](i)
      that persisted in Ca(2+)-free medium and was inhibited by 2
      aminoethoxydiphenylborane (2-APB). Application of caffeine induced a rapid spike
      like elevation in [Ca(2+)](i) that was insensitive to 2-APB but was abolished by
      pretreatment with 10 muM ryanodine. These data support the idea that both
      inositol trisphosphate (IP(3)) receptors (IP(3)R) and ryanodine receptors (RyR)
      are present in this tissue. When caffeine was applied in Ca(2+)-free solution,
      the [Ca(2+)](i) transients decreased as the interval between Ca(2+) removal and
      caffeine application was increased, indicating a possible leakage of Ca(2+) in
      these stores. The refilling of caffeine-sensitive stores involved
      sarcoendoplasmic reticulum Ca(2+)-ATPase activation, similar to IP(3)-sensitive
      stores. The moderate Ca(2+) elevation caused by CCK was associated with a
      gallbladder contraction, but caffeine or ryanodine failed to induce gallbladder
      contraction. Nevertheless, caffeine caused a concentration-dependent relaxation
      in gallbladder strips either under resting tone conditions or precontracted with
      1 muM CCK. Taken together, these results suggest that, in gallbladder smooth
      muscle, multiple pharmacologically distinct Ca(2+) pools do not exist, but IP(3)R
      and RyR must be spatially separated because Ca(2+) release via these pathways
      leads to opposite responses.

PMID- 15499079
TI  - Na(+)/Ca(2+) exchange regulates Ca(2+)-dependent duodenal mucosal ion transport
      and HCO(3)(-) secretion in mice.
AB  - Stimulation of muscarinic receptors in duodenal mucosa raises intracellular
      Ca(2+), which regulates ion transport, including HCO(3)(-) secretion. However,
      the underlying Ca(2+) handling mechanisms are poorly understood. The aim of the
      present study was to determine whether Na(+)/Ca(2+) exchanger (NCX) plays a role
      in the regulation of duodenal mucosal ion transport and HCO(3)(-) secretion by
      controlling Ca(2+) homeostasis. Mouse duodenal mucosa was mounted in Ussing
      chambers. Net ion transport was assessed as short-circuit current (I(sc)), and
      HCO(3)(-) secretion was determined by pH-stat. Expression of NCX in duodenal
      mucosae was analyzed by Western blot, and cytosolic Ca(2+) in duodenocytes was
      measured by fura 2. Carbachol (100 muM) increased I(sc) in a biphasic manner: an
      initial transient peak within 2 min and a later sustained plateau starting at 10
      min. Carbachol-induced HCO(3)(-) secretion peaked at 10 min. 2
      Aminoethoxydiphenylborate (2-APB, 100 muM) or LiCl (30 mM) significantly reduced
      the initial peak in I(sc) by 51 or 47%, respectively, and abolished the plateau
      phase of I(sc) without affecting HCO(3)(-) secretion induced by carbachol.
      Ryanodine (100 muM), caffeine (10 mM), and nifedipine (10 muM) had no effect on
      either response to carbachol. In contrast, nickel (5 mM) and KB-R7943 (10-30 muM)
      significantly inhibited carbachol-induced increases in duodenal mucosal I(sc) and
      HCO(3)(-) secretion. Western blot analysis showed expression of NCX1 proteins in
      duodenal mucosae, and functional NCX in duodenocytes was demonstrated in Ca(2+)
      imaging experiments where Na(+) depletion elicited Ca(2+) entry via the reversed
      mode of NCX. These results indicate that NCX contributes to the regulation of
      Ca(2+)-dependent duodenal mucosal ion transport and HCO(3)(-) secretion that
      results from stimulation of muscarinic receptors.

PMID- 15499080
TI  - Toll-like receptor-mediated responses of primary intestinal epithelial cells
      during the development of colitis.
AB  - The interleukin-2-deficient (IL-2(-/-)) mouse model of ulcerative colitis was
      used to test the hypothesis that colonic epithelial cells (CEC) directly respond
      to bacterial antigens and that alterations in Toll-like receptor (TLR)-mediated
      signaling may occur during the development of colitis. TLR expression and
      activation of TLR-mediated signaling pathways in primary CEC of healthy animals
      was compared with CEC in IL-2(-/-) mice during the development of colitis. In
      healthy animals, CEC expressed functional TLR, and in response to the TLR4 ligand
      LPS, proliferated and secreted the cytokines IL-6 and monocyte chemoattractant
      protein-1 (MCP-1). However, the TLR-responsiveness of CEC in IL-2(-/-) mice was
      different with decreased TLR4 responsiveness and augmented TLR2 responses that
      result in IL-6 and MCP-1 secretion. TLR signaling in CEC did not involve NF
      kappaB (p65) activation with the inhibitory p50 form of NF-kappaB predominating
      in CEC in both the healthy and inflamed colon. Development of colitis was,
      however, associated with the activation of MAPK family members and upregulation
      of MyD88-independent signaling pathways characterized by increased caspase-1
      activity and IL-18 production. These findings identify changes in TLR expression
      and signaling during the development of colitis that may contribute to changes in
      the host response to bacterial antigens seen in colitis.

PMID- 15499081
TI  - Mechanism of augmented duodenal HCO(3)(-) secretion after elevation of luminal
      CO(2).
AB  - The proximal duodenum is exposed to extreme elevations of P(CO(2)) because of the
      continuous mixture of secreted HCO(3)(-) with gastric acid. These elevations (up
      to 80 kPa) are likely to place the mucosal cells under severe acid stress.
      Furthermore, we hypothesized that, unlike most other cells, the principal source
      of CO(2) for duodenal epithelial cells is from the lumen. We hence examined the
      effect of elevated luminal P(CO(2)) on duodenal HCO(3)(-) secretion (DBS) in the
      rat. DBS was measured by the pH-stat method. For CO(2) challenge, the duodenum
      was superfused with a high Pco(2) solution. Intracellular pH (pH(i)) of duodenal
      epithelial cells was measured by ratio microfluorometry. CO(2) challenge, but not
      isohydric solutions, strongly increased DBS to approximately two times basal for
      up to 1 h. Preperfusion of the membrane-permeant carbonic anhydrase inhibitor
      methazolamide, or continuous exposure with indomethacin, fully inhibited CO(2)
      augmented DBS. Dimethyl amiloride (0.1 mM), an inhibitor of the basolateral
      sodium-hydrogen exchanger 1, also inhibited CO(2)-augumented DBS, although S
      3226, a specific inhibitor of apical sodium-hydrogen exchanger 3, did not. DIDS,
      an inhibitor of basolateral sodium-HCO(3)(-) cotransporter, also inhibited CO(2)
      augemented DBS, as did the anion channel inhibitor 5-nitro-2-(3
      phenylpropylamino) benzoic acid. CO(2) decreased epithelial cell pH(i), followed
      by an overshoot after removal of the CO(2) solution. We conclude that luminal
      CO(2) diffused in the duodenal epithelial cells and was converted to H(+) and
      HCO(3)(-) by carbonic anhydrase. H(+) initially exited the cell, followed by
      secretion of HCO(3)(-). Secretion was dependent on a functioning basolateral
      sodium/proton exchanger, a functioning basolateral HCO(3)(-) uptake mechanism,
      and submucosal prostaglandin generation and facilitated hydration of CO(2) into
      HCO(3)(-) and H(+).

PMID- 15499082
TI  - Attenuation of acute experimental colitis by preventing NPY Y1 receptor
      signaling.
AB  - Neuropeptide Y (NPY), a 36-amino acid peptide, is widely expressed in the central
      and peripheral nervous system. NPY is involved in the regulation of several
      physiological processes, including energy balance, food intake, and nociception.
      Recently, we showed that activation of the NPY Y1 receptor is required for
      cutaneous neurogenic inflammation. Because neurogenic inflammation could
      participate in colitis, the aim of this study was to investigate the role of the
      NPY Y1 receptor in acute colitis using mice genetically deficient of NPY Y1
      receptor. In addition, the Y1 receptor antagonist H409/22, was also investigated.
      Animals received 5% dextran sulfate sodium (DSS) in drinking water for 7 days.
      One group of animals also received the Y1 receptor antagonist, administered
      intraperitoneally twice daily. Disease activity was assessed daily for 7 days in
      all groups. DSS induced colitis in all animals resulting in weight loss,
      diarrhea, epithelial damage, crypt shortening, and inflammatory infiltration.
      However, clinical manifestation of the disease was markedly attenuated in Y1 null
      mutant mice as well as in mice receiving the Y1 antagonist. Histological analysis
      showed that tissue damage and ulceration were less severe in Y1-deficient
      animals. Consistent with the clinical and histological data, capsaicin-induced
      plasma extravasation was significantly reduced in the gut of Y1 null mutant
      animals compared with treated wild-type animals. These data indicate that NPY and
      Y1 receptor are involved in intestinal inflammation and suggest that inhibition
      of NPY Y1 receptor signaling may provide a novel therapeutic approach in the
      treatment of colonic inflammation.

PMID- 15499083
TI  - Evaluation of early gastric mucosal permeability induced by central thyrotropin
      releasing hormone administration.
AB  - Accumulating evidence suggests that central thyrotropin-releasing hormone (TRH)
      administration induces gastric erosion 4 h after administration through the vagal
      nerves. However, early changes in the gastric mucosa during these 4 h have not
      been described. To assess early changes in the gastric mucosa after
      intracisternal injection of a stable TRH analog, pGlu-His-(3,3'-dimethyl)-ProNH2
      (RX-77368), we measured the blood-to-lumen 51Cr-labeled EDTA clearance and
      examined the effects of vagotomy, atropine, omeprazole, and hydrochloric acid
      (HCl) on RX-77368-induced mucosal permeability. A cytoprotective dose of RX-77368
      (1.5 ng) did not increase mucosal permeability. However, higher doses
      significantly increased mucosal permeability. Permeability peaked within 20 min
      and gradually returned to control levels in response to a 15-ng dose (submaximal
      dose). Increased mucosal permeability was not recovered after a 150-ng dose
      (ulcerogenic dose). This increase in permeability was inhibited by vagotomy or
      atropine. Intragastric perfusion with HCl did not change the RX-77368 (15 ng)
      induced increase in permeability, but completely inhibited the recovery of
      permeability after the peak. Pretreatment with omeprazole did not change the RX
      77368 (15 ng)-induced increase in permeability, but quickened the recovery of
      permeability after the peak. These data indicate that the RX-77368-induced
      increase in permeability is mediated via the vagal-cholinergic pathway and is not
      a secondary change in RX-77368-induced acid secretion. Inhibited recovery of
      permeability on exposure to an ulcerogenic RX-77368 dose or on exposure to HCl
      plus a submaximal dose of RX-77368 may be crucial for the induction of gastric
      mucosal lesions by central RX-77368 administration.

PMID- 15499084
TI  - The female intestine is more resistant than the male intestine to gut injury and
      inflammation when subjected to conditions associated with shock states.
AB  - Having documented that proestrus female rats are more resistant to shock-induced
      acute gut and hence lung injury than male rats, we tested the hypothesis that the
      female gut is more resistant to injury and produces less of an inflammatory
      response than the male gut when exposed to conditions associated with shock
      states (hypoxia and acidosis) utilizing the ex vivo Ussing chamber system. Ileal
      mucosal membranes harvested from normal male and female rats mounted in Ussing
      chamber systems were exposed to normoxia or 40 min of hypoxia at a normal pH (pH
      7.3) or acidosis (pH 6.8). Cytokine and nitric oxide levels in the serosal
      compartment of the Ussing chamber were measured at the end of the 3-h
      experimental period to assess the immunoinflammatory response, whereas FITC
      dextran (mol wt 4,300) was employed to assess barrier function.
      Histomorphological changes were used to quantitate gut mucosal injury. Hypoxia,
      acidosis, or hypoxia plus acidosis was associated with a significant increase in
      proinflammatory cytokine production [interleukin (IL)-6, tumor necrosis factor,
      and macrophage inflammatory protein (MIP)-2] by the male compared with the female
      intestinal segments. In contrast, the female gut manifested a higher anti
      inflammatory response (nitric oxide and IL-10) and improved intestinal barrier
      function as well as less evidence of mucosal injury than the male intestinal
      segments. Administration of estradiol or the testosterone receptor antagonist,
      flutamide, to male rats abrogated the increase in gut injury and the increased IL
      6 and MIP-2 response observed after hypoxia plus acidosis. These results suggest
      that gender differences in the ex vivo intestinal response to stresses, such as
      hypoxia and acidosis, exist and that the administration of estradiol or blockade
      of the testosterone receptor to male rats mitigates these gender differences.

PMID- 15499085
TI  - Placebos in practice.

PMID- 15499086
TI  - What causes chronic fatigue syndrome?

PMID- 15499087
TI  - Reforming the consultant contract again?

PMID- 15499088
TI  - Computed tomography in children.

PMID- 15499089
TI  - Back to the future?

PMID- 15499090
TI  - Safety of antipsychotic drugs for pregnant and breastfeeding women with non
      affective psychosis.

PMID- 15499091
TI  - Pfizer criticised over delay in admitting drug's problems.

PMID- 15499092
TI  - US government agency to investigate FDA over rofecoxib.

PMID- 15499093
TI  - US presidential candidates clash over health care.

PMID- 15499094
TI  - Consumer organisations criticise influence of drug companies.

PMID- 15499095
TI  - Indian doctors debate incentives for organ donors.

PMID- 15499098
TI  - Surgeon found liable for not warning of partial paralysis risk.

PMID- 15499099
TI  - UK body calls on UN to allow therapeutic cloning.

PMID- 15499100
TI  - US health workers who give flu jabs to healthy people could face fines or
      imprisonment.

PMID- 15499101
TI  - Doctors favour legalising assisted suicide for dying patients.

PMID- 15499109
TI  - US and UK scientists disagree about causes of Gulf war syndrome.

PMID- 15499110
TI  - Infectious diseases increase in Iraq as public health service deteriorates.

PMID- 15499112
TI  - Risks of general anaesthesia in people with obstructive sleep apnoea.

PMID- 15499113
TI  - Childhood leukaemia masquerading as juvenile idiopathic arthritis.

PMID- 15499114
TI  - Respiratory complications of preterm birth.

PMID- 15499115
TI  - Individual response to treatment: is it a valid assumption?

PMID- 15499116
TI  - The PROGRESS trial three years later: time for a balanced report of
      effectiveness.

PMID- 15499117
TI  - The PROGRESS trial three years later: time for more action, less distraction.

PMID- 15499118
TI  - Inclusion of cost effectiveness in licensing requirements of new drugs: the
      fourth hurdle.

PMID- 15499119
TI  - Winter mortality in elderly people in Britain: lack of social gradient in winter
      excess mortality is obvious in Denmark.

PMID- 15499120
TI  - Winter mortality in elderly people in Britain: outdoor exposure and effect of
      windchill should be taken into consideration.

PMID- 15499121
TI  - Winter mortality in elderly people in Britain: action on outdoor cold stress is
      needed to reduce winter mortality.

PMID- 15499122
TI  - Bioterrorism and compulsory vaccination: arguments for current vaccines are based
      on inadequate support for older vaccines.

PMID- 15499123
TI  - Bioterrorism and compulsory vaccination: United States continues vaccinating to
      keep troops healthy.

PMID- 15499124
TI  - Preventing the spread of MRSA: ...and the role of practices such as phlebotomy is
      worth considering.

PMID- 15499125
TI  - Preventing the spread of MRSA: ...the epidemiological nature of the problem
      should be tackled...

PMID- 15499126
TI  - Preventing the spread of MRSA: all frontline staff need to be involved...

PMID- 15499127
TI  - Private sector needs incentives for AIDS vaccine.

PMID- 15499128
TI  - Health needs of Zimbabweans are poorly recognised in UK.

PMID- 15499129
TI  - Treatment of impetigo: save mupirocin.

PMID- 15499130
TI  - Treatment of impetigo: paint it blue.

PMID- 15499131
TI  - Medication errors in the neonatal intensive care unit: special patients, unique
      issues.

PMID- 15499132
TI  - Taurine in neonatal nutrition--revisited.

PMID- 15499133
TI  - Neonatal coagulation problems.
AB  - Bleeding problems often occur during the neonatal period. Although
      thrombocytopenia is the most common cause, coagulation problems often occur, and
      the two problems may co-exist. The causes, diagnosis, and management of
      coagulation problems in newborn infants are reviewed.

PMID- 15499134
TI  - Monoamniotic twin pregnancy: a hazardous fetal life.

PMID- 15499135
TI  - Reducing medication errors in the neonatal intensive care unit.
AB  - BACKGROUND: Medication errors are common in the neonatal intensive care unit
      (NICU). Various strategies to reduce errors have been described in adult and
      paediatric patients but there are few published data on their effect in the NICU.
      AIM: To describe the medication errors occurring within an NICU, and assess the
      impact of a combined risk management/clinical pharmacist led education programme
      on these errors. METHODS: Medication errors were identified prospectively over
      one year by critical incident reporting. Four months into the study, a pharmacist
      led education programme was instituted. This involved a daily, cot side,
      pharmacist led review of medication orders. Each new member of pharmacy, nursing,
      or medical staff was also required to successfully complete a series of dose
      calculations. In addition, a risk management approach was used to make several
      changes in practice during the study period. RESULTS: A total of 105 errors were
      identified, four serious, 45 potentially serious, and 56 minor. The four serious
      errors included two tenfold dose miscalculations. Most (71%) of the errors were
      due to poor prescribing. After the introduction of our interventions, monthly
      medication errors fell from a mean (SD) of 24.1 (1.7) per 1000 neonatal activity
      days to 5.1 (3.6) per 1000 days (p < 0.001) in the following three months. The
      subsequent change over of junior medical staff was associated with a significant
      increase in medication errors to 12.2 (3.6) per 1000 neonatal activity days (p =
      0.037). However, the number remained significantly less than before our
      interventions (p < 0.001). Three serious errors occurred in the first four months
      compared with one in the second eight month period, the latter corresponding to
      the six monthly change over of junior medical staff. CONCLUSIONS: Medication
      errors are common in NICUs. Fortunately, actual harm to an infant is rare.
      Interventions to reduce errors, particularly within the context of a risk
      management programme, are effective.

PMID- 15499136
TI  - Potential tenfold drug overdoses on a neonatal unit.
AB  - Nearly one third of intravenous drug prescriptions on a neonatal unit were for
      doses less than one tenth of a single drug vial. Tenfold drug errors in
      prescribing are well documented and with the continued use of vials containing
      adult size doses, great potential exists for serious administration errors.

PMID- 15499137
TI  - The laryngeal mask airway: potential applications in neonates.
AB  - The laryngeal mask airway is a safe and reliable airway management device. This
      review describes the insertion techniques, advantages, limitations, and potential
      applications of the laryngeal mask airway in neonates.

PMID- 15499138
TI  - Comparison of three manual ventilation devices using an intubated mannequin.
AB  - OBJECTIVE: To compare three devices for manual neonatal ventilation. DESIGN:
      Participants performed a two minute period of ventilation using a self inflating
      device, an anaesthesia bag with attached manometer, and a Neopuff device. An
      intubated neonatal mannequin, approximating a 1 kg infant with functional lungs,
      was used for the study. Target ventilation variables included a rate of 40
      breaths per minute, peak inspiratory pressure (PIP) of 20 cm H2O, and positive
      end expiratory pressure (PEEP) of 4 cm H2O. The circuit was attached to a laptop
      computer for data recording. RESULTS: Thirty five participants were enrolled,
      including consultant neonatologists, paediatricians, and anaesthetists,
      paediatric and anaesthetic registrars, and neonatal nurses. The maximum PIP
      recorded using the self inflating bag, anaesthetic bag, and Neopuff device were
      75.9, 35.5, and 22.4 cm H2O respectively. There were significant differences
      between the devices for mean PIP (30.7, 18.1, and 20.1 cm H2O), mean PEEP (0.2,
      2.8, and 4.4 cm H2O), mean airway pressure (7.6, 8.5, and 10.9 cm H2O), % total
      breaths < or = 21 cm H2O PIP (39%, 92%, and 98%), and % total breaths > or = 30
      cm H2O PIP (45%, 0, and 0). There was no difference between doctors and allied
      health professionals for the variables examined. CONCLUSION: The anaesthetic bag
      with manometer and Neopuff device both facilitate accurate and reproducible
      manual ventilation. Self inflating devices without modifications are not as
      consistent by comparison and should incorporate a manometer and a PEEP device,
      particularly when used for resuscitation of very low birthweight infants.

PMID- 15499139
TI  - A randomised comparison of resuscitation with an anaesthetic rebreathing circuit
      or an infant ventilator in very preterm infants.
AB  - Twenty four preterm infants (< 27 weeks gestation) were randomised to
      resuscitation with an anaesthetic rebreathing circuit or a ventilator with volume
      guarantee. There was no difference in weight or gestation between the groups. End
      expiratory pressures were higher and less variable with the ventilator. This
      pilot study shows that very preterm infants can be safely and effectively
      resuscitated using a ventilator.

PMID- 15499140
TI  - Low plasma taurine and later neurodevelopment.
AB  - Dietary taurine intake may explain the benefits of both breast milk and preterm
      formula to neurodevelopment. Low plasma neonatal taurine was associated with
      lower scores on the Bayley mental development index at 18 months and the WISC-R
      arithmetic subtest at 7 years. Currently it is not mandatory to add taurine to
      infant formulas.

PMID- 15499141
TI  - High dose caffeine citrate for extubation of preterm infants: a randomised
      controlled trial.
AB  - OBJECTIVE: To compare two dosing regimens for caffeine citrate in the
      periextubation period for neonates born at less than 30 weeks gestation in terms
      of successful extubation and adverse effects. DESIGN: A multicentre, randomised,
      double blind, clinical trial. SETTING: Four tertiary neonatal units within
      Australia. PATIENTS: Infants born less than 30 weeks gestation ventilated for
      more than 48 hours. INTERVENTIONS: Two dosing regimens of caffeine citrate (20 v
      5 mg/kg/day) for periextubation management. Treatment started 24 hours before a
      planned extubation or within six hours of an unplanned extubation. MAIN OUTCOME
      MEASURE: Failure to extubate within 48 hours of caffeine loading or reintubation
      and ventilation or doxapram within seven days of caffeine loading. RESULTS: A
      total of 234 neonates were enrolled. A significant reduction in failure to
      extubate was shown for the 20 mg/kg/day dosing group (15.0% v 29.8%; relative
      risk 0.51; 95% confidence interval (CI) 0.31 to 0.85; number needed to treat 7
      (95% CI 4 to 24)). A significant difference in duration of mechanical ventilation
      was shown for infants of less than 28 weeks gestation receiving the high dose of
      caffeine (mean (SD) days 14.4 (11.1) v 22.1 (17.1); p = 0.01). No difference in
      adverse effects was detected in terms of mortality, major neonatal morbidity,
      death, or severe disability or general quotient at 12 months. CONCLUSIONS: This
      trial shows short term benefits for a 20 mg/kg/day dosing regimen of caffeine
      citrate for neonates born at less than 30 weeks gestation in the periextubation
      period, without evidence of harm in the first year of life.

PMID- 15499142
TI  - Central venous lines in neonates: a study of 2186 catheters.
AB  - OBJECTIVE: To describe the use of percutaneously inserted silicone central venous
      lines (CVLs) in neonates at the Royal Brisbane and Women's Hospital, Australia.
      DESIGN: Data for all infants admitted from 1 January 1984 until 31 December 2002
      who had a CVL were examined in the neonatal database, completed from paper
      records and patient charts where necessary. Autopsy reports of all babies who
      died with a catheter in place were reviewed. RESULTS: There were 18,761
      admissions, 2186 catheters in 1862 babies for a total of 35,159 days (median 14
      days, range 1-99 days). The tip was in the right atrium for 1282 (58.6%) of the
      catheters. A total of 142 babies (7.6%) died with a CVL in place, 89 (4.8%) with
      the catheter tip in the right atrium. Thirty two of these 89 babies had an
      autopsy. No autopsies reported tension in the pericardium or milky fluid
      resembling intralipid. One case (0.05% of catheters) of non-lethal pericardial
      effusion occurred in a baby whose catheter was inappropriately left coiled in the
      right atrium. There were no cases of pleural effusion related to CVL use. Most
      (1523, 69.7%) were removed electively. Septicaemia occurred during the life of
      116 catheters (5.3%). CONCLUSION: This is the largest series of percutaneously
      inserted silicone central venous catheters reported. It illustrates the safety of
      these catheters in this context. It highlights the value of keeping prospective
      records on such catheters. Catheters with their tips in the right atrium and not
      coiled did not cause pericardial effusion. Strict insertion and management
      principles for CVLs should be adhered to.

PMID- 15499143
TI  - Does human milk reduce infection rates in preterm infants? A systematic review.
AB  - One of the reasons for advocating human milk (HM) feeding for preterm infants is
      the belief that this provides the infant with a degree of protection from
      infection. Providing fresh HM for such infants is challenging for mothers and
      staff, and consequently it is important that its benefits are rigorously
      evaluated. Therefore a systematic review was undertaken to assess all
      publications concerned with human milk feeding and infection in very low birth
      weight (VLBW) preterm infants. Nine studies--six cohort and three randomised
      controlled trials (RCT)--were assessed using predefined criteria. Methodological
      problems included poor study design, inadequate sample size, failure to adjust
      for confounding variables, and inadequate definitions of HM feeding and outcome
      measures. In conclusion, the advantage of HM in preventing infection in preterm,
      (VLBW) infants is not proven by the existing studies. Recommendations are made
      regarding the methodology required for further study of this important topic.

PMID- 15499144
TI  - Increased osmolality of breast milk with therapeutic additives.
AB  - AIM: To evaluate the changes in the osmolality of expressed breast milk (EBM)
      after the addition of seven additives and four proprietary fortifiers commonly
      used during neonatal intensive care. METHODS: The osmolality of 5 ml EBM was
      measured with increasing doses of 6% NaCl, caffeine, sodium ironedetate, folic
      acid, and multivitamin drops. Sodium acid phosphate and chloral hydrate were
      added to 8 ml EBM, and the fortifiers were added to standard volumes of EBM. Dose
      effect curves were plotted, and the volume of milk that must be added to the
      above additives to maintain osmolality below 400 mOsm/kg was calculated. RESULTS:
      The osmolality of the pure additives ranged from 242 to 951 mOsm/kg. There was a
      significant increase in the osmolality of EBM with increasing doses of all
      additives except caffeine. The osmolality of EBM with many additives in
      clinically used dosages potentially exceeded 400 mOsm/kg. The greatest increase
      occurred with sodium ironedetate syrup, where the osmolality of EBM increased to
      951.57 (25.36) mOsm/kg. Proprietary fortifiers increased the osmolality of EBM to
      a maximum of 395 mOsm/kg. CONCLUSION: Routine additives can significantly
      increase the osmolality of EBM to levels that exceed current guidelines for
      premature infant feeding. A simple guide for clinical use is presented, which
      indicates the amount of milk required as diluent if hyperosmolality is to be
      avoided.

PMID- 15499145
TI  - Effect of storage on breast milk antioxidant activity.
AB  - BACKGROUND: Human milk, which contains compounds beneficial to infants, is often
      expressed and stored before use. Changes in its antioxidant activity with storage
      have not been studied. OBJECTIVES: To measure antioxidant activity of fresh,
      refrigerated (4 degrees C), and frozen human milk (-20 degrees C), stored for two
      to seven days; to compare the antioxidant activity of milk from mothers
      delivering prematurely and at term; to compare the antioxidant activity of infant
      formulas and human milk. METHODS: Sixteen breast milk samples (term and preterm)
      were collected from mothers within 24 hours of delivery and divided into
      aliquots. Fresh samples were immediately tested for antioxidant activity, and the
      rest of the aliquots were stored at -20 degrees C or 4 degrees C to be analysed
      at 48 hours and seven days respectively. The assay used measures the ability of
      milk samples to inhibit the oxidation of 2,2'-azino-di-3
      (ethylbenzthiazolinesulphonate) to its radical cation compared with Trolox.
      RESULTS: Antioxidant activity at both refrigeration and freezing temperatures was
      significantly decreased. Freezing resulted in a greater decrease than
      refrigeration, and storage for seven days resulted in lower antioxidant activity
      than storage for 48 hours. There was no difference in milk from mothers who
      delivered prematurely or at term. Significantly lower antioxidant activity was
      noted in formula milk than in fresh human milk. CONCLUSIONS: To preserve the
      antioxidant activity of human milk, storage time should be limited to 48 hours.
      Refrigeration is better than freezing and thawing.

PMID- 15499146
TI  - Census of neonatal transfers in London and the South East of England.
AB  - OBJECTIVES: To determine the number and characteristics of inter-hospital
      transfers of newborn infants in London and the South East of England. DESIGN:
      Prospective census of neonatal transfers over a three month period. SETTING:
      Transfers between the 53 hospitals that provide care for newborn infants within
      the former Thames regions. DATA SOURCES: Census returns from participating
      neonatal units. MAIN OUTCOME MEASURES: Number, timing, and hours of staff time
      spent on transfers. Gestation, birth weight, and reason for transfer of the baby.
      Time elapsed between request and retrieving team departing and arriving with
      patient. RESULTS: A daily average of 2.7 urgent, 3.5 elective, and 0.7 short term
      transfers took place during the census period. The most common reason for urgent
      transfer was neonatal surgery. Neonatal unit staff spent an average of 21 hours a
      day off their units accompanying transfers each day. It took over four hours for
      90% of ambulances to set off with the retrieving team and over six hours for 90%
      of teams to reach the baby. CONCLUSIONS: During the census period, services for
      the transport of neonates in London and the South East of England involved long
      delays and used appreciable amounts of staff time. It is likely that a small
      number of dedicated neonatal transfer teams could meet the needs identified in
      this census more effectively than the 53 hospitals currently involved.

PMID- 15499148
TI  - Palpebral ecchymosis and cerebral venous thrombosis in a near term infant.

PMID- 15499147
TI  - Decision making and modes of death in a tertiary neonatal unit.
AB  - AIMS: To study the frequency and reason for withdrawal/withholding of life
      sustaining treatment (LST) and do not resuscitate (DNR) orders in infants who
      died in a tertiary neonatal unit. METHODS: Infants who died at Homerton
      University Hospital between January 1998 and September 2001 were studied by
      retrospective analysis of patient records. RESULTS: The case notes of 71 (84%) of
      85 infants who died were studied. Mode of death was withdrawal of LST in 28
      (40%), DNR in 11 (15%), withholding of LST in two (3%), and natural in 30 (42%)
      infants. Withdrawal of LST was discussed with the parents of 39 seriously ill
      infants; 28 (72%) parents agreed. There was no difference in birth weight and
      gestational age of babies whose parents agreed or refused withdrawal of LST.
      White and Afro-Caribbean parents and those from the Indian subcontinent (20 of
      23) were more likely to agree to withdrawal of LST than Black African or Jewish
      (eight of 16, p = 0.015) parents. The median age at withdrawal of LST was 4 days
      (range 1-57). The median duration between discussion and the parents agreeing to
      withdrawal of LST was 165 minutes (range 30-2160), and median duration between
      withdrawal of LST and death was 22 minutes (range 5-210). The most common reason
      for withdrawal of LST was complications of extreme prematurity (68%). CONCLUSION:
      The most common mode of death was withdrawal of LST, and the most common reason
      was complications of extreme prematurity. The ethnic and cultural background of
      the parents influenced agreement to withdrawal of LST.

PMID- 15499149
TI  - Changing patterns of perinatal death, 1982-2000: a retrospective cohort study.
AB  - OBJECTIVE: To describe trends in cause specific stillbirth and neonatal
      mortality. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: 686,860
      births in 1982-2000, to mothers resident in the Northern Region of England. MAIN
      OUTCOME MEASURES: Cause specific stillbirth and neonatal mortality; rate ratios
      (RR) and 95% confidence intervals (CI) in 1991-2000 compared with 1982-1990.
      RESULTS: In singletons, rates of stillbirth and neonatal mortality declined over
      time (RR stillbirths, 0.81 (95% CI 0.76 to 0.87); RR neonatal mortality, 0.76
      (95% CI 0.70 to 0.82)). Death from congenital anomalies declined substantially
      for both stillbirths (RR 0.52; 95% CI 0.40 to 0.68) and neonatal mortality (RR
      0.58; 95% CI 0.51 to 0.67). Mortality due to intrapartum hypoxia also fell, by
      nearly 50% for stillbirths and 30% for neonatal deaths. There was no reduction in
      stillbirths due to antepartum hypoxia in babies weighing > or = 2500 g, or in
      mortality attributed to infection. In multiples, the risk of death was higher (RR
      stillbirths, 4.13 (95% CI 3.68 to 4.64); RR neonatal death, 7.82 (95% CI 7.13 to
      8.58)). Stillbirth rates declined significantly (RR 0.71; 95% CI 0.57 to 0.89)
      but neonatal mortality did not (RR 0.91; 95% CI 0.77 to 1.08). There was no
      reduction in neonatal mortality resulting from prematurity, or in mortality from
      congenital anomalies. CONCLUSIONS: There is considerable overlap in the causes of
      stillbirth and neonatal mortality. Future progress in reducing perinatal
      mortality requires better understanding of the aetiology of antepartum
      stillbirth, of the excess risks of prematurity facing multiple births,
      particularly in the light of their increasing incidence, and of strategies to
      prevent perinatal infection.

PMID- 15499150
TI  - Postoperative pain assessment in the neonatal intensive care unit.
AB  - OBJECTIVES: To compare the convergent validity of two measures of pain (premature
      infant pain profile (PIPP) and crying, requires oxygen, increased vital signs,
      expression, and sleepless (CRIES)) in real life postoperative pain assessment in
      infants. METHODS: This study was a prospective, repeated measures, correlational
      design. Two staff nurses were randomly assigned either the PIPP or CRIES measure.
      An expert rater assessed each infant after surgery, and once a day using the
      visual analogue scale (VAS). SETTING: A level III neonatal intensive care unit in
      a metropolitan university affiliated paediatric hospital. RESULTS: Pain was
      assessed in 51 neonates (28-42 weeks of gestational age) after surgery. There was
      no significant difference in the rates of change between the pain assessment
      measures across time using repeated measures analysis of variance (F(50,2) =
      0.62, p = 0.540), indicating correlation between the measures. Convergent
      validity analysis using intraclass correlation showed correlation, most evident
      in the first 24 hours (immediately, 4, 8, 20, and 24 hours after the operation).
      Correlations were more divergent at 40 and 72 hours after surgery. No significant
      interactions were found between gestational age and measure (F(304,4) = 0.75, p =
      0.563) and surgical group and measure (F(304,2) = 0.39, p = 0.680). CONCLUSIONS:
      PIPP and CRIES are valid measures that correlate with pain for the first 72 hours
      after surgery in term and preterm infants. Both measures would provide healthcare
      professionals with an objective measure of a neonatal patient's pain.

PMID- 15499151
TI  - Economic implications of multiple births: inpatient hospital costs in the first 5
      years of life.
AB  - OBJECTIVES: To estimate long term health service costs for hospital stays
      associated with singleton, twin, and higher order multiple births up to 5 years
      of age. DESIGN: Costs from specialty based data from the English Department of
      Health's NHS Trust Financial Returns were applied to admissions recorded in the
      Oxford record linkage study during 1970-1993. SETTING: Oxfordshire and West
      Berkshire, United Kingdom. SUBJECTS: A total of 276,897 children, of whom 270,428
      were singletons, 6284 were twins, and 185 were higher order multiple births. MAIN
      OUTCOME MEASURES: Duration of hospital admissions during the first 5 years of
      life. Costs, expressed in pound sterling and valued at 1998-1999 prices, of
      hospital inpatient services. RESULTS: The total duration of hospital admissions
      for twins and triplets were respectively twice and eight times that for
      singletons, once duration of life had been taken into account. Inpatient costs
      were significantly higher for multiple births than for singletons, with the cost
      differences concentrated in the first year of life. Over the first 5 years of
      life, the adjusted mean cost was estimated at 1532 pounds (95% confidence
      interval (CI) 1516 pounds to 1548 pounds) for singletons, 3826 pounds (95%CI 3724
      pounds to 3929 pounds) for twins, and 8156 pounds (95%CI 7559 pounds to 8754
      pounds) for higher order multiple births (p < 0.0001). CONCLUSIONS: Multiple
      births contribute disproportionately to hospital inpatient costs, especially
      during the children's first year of life.

PMID- 15499152
TI  - Intracranial haemorrhage due to late onset vitamin K deficiency bleeding in Hanoi
      province, Vietnam.
AB  - BACKGROUND: In many developing countries vitamin K prophylaxis is not routinely
      administered at birth. There are insufficient data to assess the cost
      effectiveness of its implementation in such countries. OBJECTIVE: To estimate the
      burden of intracranial haemorrhage caused by late onset vitamin K deficiency
      bleeding in Hanoi, Vietnam. METHODS: Cases of intracranial haemorrhage in infants
      aged 1-13 weeks were identified in Hanoi province for 5 years (1995-1999), and
      evidence for vitamin K deficiency was sought. The data were compared with those
      on vitamin K deficiency bleeding in developed countries and used to obtain an
      approximation to the incidence of intracranial haemorrhage caused by vitamin K
      deficiency bleeding in Hanoi. RESULTS: The estimated incidence of late onset
      vitamin K deficiency bleeding in infants who received no prophylaxis was
      unexpectedly high (116 per 100,000 births) with 142 and 81 per 100,000 births in
      rural and urban areas respectively. Mortality was 9%. Of the surviving infants,
      42% were neurologically abnormal at the time of hospital discharge. Identified
      associations were rural residence, male sex, and low birth weight. A significant
      reduction in the incidence was observed in urban Hanoi during 1998 and 1999,
      after vitamin K prophylaxis was introduced at one urban obstetric hospital.
      CONCLUSIONS: Vitamin K deficiency bleeding is a major public health problem in
      Hanoi. The results indicate that routine vitamin K prophylaxis would
      significantly reduce infant morbidity and mortality in Vietnam and, costing an
      estimated 87 US dollars (48 pounds, 72 Euro) per disability adjusted life year
      saved, is a highly cost effective intervention.

PMID- 15499153
TI  - Lipopolysaccharide binding protein in preterm infants.
AB  - OBJECTIVE: To assess serum concentrations of lipopolysaccharide binding protein
      (LBP) in preterm infants with neonatal bacterial infection (NBI). METHODS: Blood
      samples were analysed of 57 preterm (28(+1) to 36(+6), median 33(+2) weeks
      gestation) and 17 term infants admitted to the neonatal intensive care unit
      within the first 72 hours of life with suspicion of NBI. Samples were obtained at
      first suspicion of sepsis and after 12 and 24 hours. Diagnosis of NBI was
      confirmed by raised concentrations of C reactive protein and/or interleukin 6.
      The influence of gestational age and labour was analysed. RESULTS: Maximum LBP
      concentrations in infants with NBI were greatly increased compared with infants
      without NBI (13.0-46.0 microg/ml (median 20.0 microg/ml) v 0.6-17.4 microg/ml
      (median 4.2 microg/ml)). LBP concentrations in infected infants were not yet
      significantly raised when NBI was first suspected. The LBP concentrations of
      preterm infants were comparable to those of term infants. Regression analysis
      revealed no significant effect of labour or gestational age on LBP. CONCLUSIONS:
      Raised LBP concentrations indicate NBI in preterm and term infants. Preterm
      infants of > 28 weeks gestation seem to be capable of producing LBP as
      efficiently as term infants. Neonatal LBP concentrations are not influenced by
      labour. LBP may be a useful diagnostic marker of NBI in preterm infants.

PMID- 15499154
TI  - Glucose-6-phosphate dehydrogenase activity in male premature and term neonates.
AB  - BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) activity is higher in term
      neonates than in adults. Some studies have suggested that activity may be even
      higher in preterm infants. OBJECTIVES: To determine if G6PD activity is higher in
      preterm than term neonates, and whether higher activity would interfere with
      diagnosis of G6PD deficiency in premature infants. METHODS: G6PD activity was
      determined in the first 48 hours after delivery in male premature, term, and near
      term infants. G6PD deficient neonates were separated, and the remaining premature
      infants compared with healthy, male, G6PD normal, near term and term neonates.
      RESULTS: Ninety four premature infants (mean (SD) gestational age 31.9 (3.8)
      weeks (range 23-36)) were studied. In four, G6PD activity was 0.8-1.8 U/g
      haemoglobin (Hb), which is clearly in the deficient range with no overlap into
      the normal range. G6PD activity in the remaining premature infants was
      significantly higher than in 24 near term and term neonates (gestational age > or
      = 37 weeks) (14.2 (4.6) v 12.0 (3.8) U/g Hb). Further analysis showed that
      significance was limited to those born between 29 and 32 weeks gestation, in
      which group G6PD activity was significantly higher than in those born before 29
      weeks gestation, at 33-36 weeks gestation, and > or = 37 weeks gestation.
      CONCLUSIONS: G6PD activity is higher in premature infants born between 29 and 32
      weeks gestation than in term neonates. This did not interfere with diagnosis of
      G6PD deficiency.

PMID- 15499155
TI  - Testosterone measurements in early infancy.
AB  - Circulating testosterone concentrations in infants measured by a direct
      chemiluminescent immunoassay (Bayer ADVIA Centaur) were compared with those
      measured by a traditional radioimmunoassay using solvent extraction. The results
      confirm that neonatal circulating testosterone concentrations are method
      dependent, and each laboratory should establish method related reference ranges
      especially if using a direct commercial immunoassay. The results indicate that
      the Bayer ADVIA Centaur procedure can be used reliably in neonates. Expected
      values for male and female infants < 10 days old were 2.5-11.1 (n = 36) and 1.7
      5.6 (n = 36) nmol/l respectively. For older neonates (10-50 days) the ranges were
      0.2-17.2 (n = 42) and 0.1-1.5 (n = 7) nmol/l respectively.

PMID- 15499156
TI  - Catherina Schrader (1656-1746): the memoirs of a Friesian midwife.
AB  - Catherina Schrader, a Dutch midwife practicing 300 years ago, left records of
      some 4000 deliveries, 95% of which were spontaneous without intervention. The
      corrected maternal mortality was 4.6/1000 and perinatal mortality 54/1000 births.

PMID- 15499157
TI  - Time is of the essence.

PMID- 15499158
TI  - US bioethics fall short of world standards.

PMID- 15499159
TI  - Pain relief during common neonatal procedures: a survey.

PMID- 15499160
TI  - Is mesenteric blood flow compromised during phototherapy in preterm neonates?

PMID- 15499161
TI  - Atrial flutter in preterm babies.

PMID- 15499162
TI  - The truth about silver.
AB  - Interest in silver as a topical agent in wound healing is undergoing a
      renaissance. Having basic information regarding silver's chemical properties and
      potential actions in the wound bed is important to its appropriate clinical use.
      Such information is also relevant to the interpretation of silver's in vitro
      antimicrobial (antiseptic) effects, which in turn relate to issues involved in
      the evaluation of the clinical effects of silver in vivo. Gaining an
      understanding of the basic science of silver products and the different
      challenges inherent to in vitro versus in vivo antimicrobial evaluations will
      allow clinicians to address several key questions inherent when considering the
      use of silver as a topical antimicrobial: 1) Are there different forms of silver?
      2) How does the amount of silver released into the wound environment correlate
      with clinical benefit? 3) How does the rate of silver release correlate with
      clinical benefit?

PMID- 15499163
TI  - Silver dressings in clinical practice.
AB  - Silver is among several topical antiseptics that are once again gaining
      popularity due, in part, to the rise of antibiotic-resistant genotypes. Because
      of differences in wounds and the variety of products--including various silver
      vehicles--available to treat them, all of the dressing characteristics
      appropriate for the specific wound being managed must be considered. This article
      addresses why silver is (and is not) a good choice for particular wounds and
      offers suggestions about what silver products best serve individual situations.

PMID- 15499164
TI  - Functional evaluation of ABCB1 (P-glycoprotein) polymorphisms: high-speed
      screening and structure-activity relationship analyses.
AB  - Evidence is accumulating to strongly suggest that drug transporters are one of
      the determinant factors governing the pharmacokinetic profile of drugs. Effort
      has been made to identify genetic variation in drug transporter genes. In
      particular, genetic variations of the human ABCB1 (MDR1) gene have been most
      extensively studied. Hitherto more than fifty single nucleotide polymorphisms
      (SNPs) and insertion/deletion polymorphisms in the ABCB1 gene have been reported.
      However, at the present time, information is still limited with respect to the
      actual effect of those genetic polymorphisms on the function of ABCB1. In this
      context, we have undertaken functional analyses of ABCB1 polymorphisms. To
      quantify the impact of genetic polymorphisms on the substrate specificity of
      ABCB1, we have developed a high-speed screening system and a new structure
      activity relationship (SAR) analysis method. This review addresses functional
      aspects of the genetic polymorphism of ABCB1 and provides the standard method to
      evaluate the effect of polymorphisms on the function.

PMID- 15499165
TI  - Pharmacokinetic comparison of an angiotensin II receptor antagonist, telmisartan,
      in Japanese and western hypertensive patients using population pharmacokinetic
      method.
AB  - The objectives of this study were to develop a population pharmacokinetic (PPK)
      model for telmisartan based on the pooled data obtained from the different racial
      populations and then to identify the factors that affect the pharmacokinetics of
      telmisartan for the comparison between the regions. A PPK model was established
      based on the data of 1343 subjects in 12 clinical trials. The PK profiles of
      telmisartan were described with a 2-compartment model with first-order
      absorption. The obtained model could predict the observed plasma concentrations
      well. This PPK model suggested that CL/F was a function of age, dose, gender,
      race, alcohol consumption and liver function. A marked difference was observed in
      the plasma concentration profiles between Japanese and other countries' subjects.
      However, the effect of the factor "race" on CL/F was not large. In the present
      PPK model, "trial condition" affected all PK parameters except for V(2)/F. The
      condition differences were in food condition and formulation (Japanese: fed,
      capsule, US and EU: fasted, tablet). The extent of difference in the plasma
      concentration profiles simulated for Japanese and Caucasian using the PPK model
      under the same demographic condition was comparable with the results of the food
      effect study performed previously in Japan. The findings suggest that the
      difference in the plasma concentration profiles between Japanese and other
      countries' subjects was mainly due to the difference of food intake conditions
      under which the clinical trials were performed.

PMID- 15499166
TI  - Relationship between pharmacokinetic parameters and occurrence of adverse events
      in clinical trials performed in Europe and United States for an angiotensin II
      receptor antagonist, telmisartan.
AB  - The objective of this study was to clarify the relationship between the
      pharmacokinetic parameters of telmisartan and the occurrence of adverse events.
      In order to perform this study, a total of 1500 adverse events was collected from
      the eight clinical trials performed in Europe and the United States and the
      pharmacokinetic parameters (C(max) and AUC) were calculated with the parameters
      obtained from the population pharmacokinetic model which we have built. Using
      these data, the pharmacokinetic parameters (C(max) and AUC) were compared between
      subjects with or without the occurrence of adverse events. The Mann-Whitney test
      was performed to analyze ten adverse events selected based on the order of
      frequency. For eight of these ten adverse events, no significant between-group
      difference was observed in any pharmacokinetic parameter. For two adverse events,
      pain and sinusitis, the pharmacokinetic parameters, C(max) and AUC, were greater
      in subjects with adverse events as compared with those without adverse events,
      but the intersubject variability of pharmacokinetic parameters was large and
      there were many subjects in whom C(max) and AUC were high without any adverse
      event. These results suggest that there is no clear relationship between
      pharmacokinetic parameters of telmisartan and the occurrence of adverse events.

PMID- 15499167
TI  - Lipopolysaccharide transport system across colonic epithelial cells in normal and
      infective rat.
AB  - To clarify whether lipopolysaccharide (LPS) is transported in rat intestinal
      epithelial cells, the transport of FITC-LPS across colonic epithelial cells in
      normal and LPS-exposured rats using a diffusion chamber was examined. The
      expression of CD14 and Toll-like receptor 4 (TLR4) was also examined. Rats were
      given 10 mg/kg LPS i.p. injection at 4 hr prior to the isolation of colonic
      epithelial tissues. The permeation rate across colonic mucosa by FITC-LPS was
      several times greater in the mucosal to serosal (M to S) direction than in the
      opposite direction in both normal and LPS-exposured rats. Increased M to S
      permeation by FITC-LPS was evident at 37 degrees C, but not at 4 degrees C. The
      permeability of FITC-LPS in both the M to S and S to M directions was inhibited
      by unlabeled LPS, anti-CD14 antibody or anti-TRL4 antibody in normal rat. In LPS
      exposured rat, the inhibition in the M to S direction was observed by anti-TLR4
      antibody, but not by unlabeled LPS and anti- CD14 antibody. In contrast, the
      permeability in the S to M direction was decreased only by unlabeled LPS in LPS
      exposured rat. In normal rat, the expression of CD14 and TLR4 was found in the
      mucosal and serosal sides. In LPS-exposured rat, the expression of CD14 was not
      observed in the mucosal side. The electrophysiological parameters by LPS exposure
      remain unchanged. These findings suggest the possibility that colonic epithelial
      cells contain specific transport systems for LPS, one of which shows some degree
      of substrate specificity with the interaction of CD14 and/or that of TLR4.

PMID- 15499168
TI  - Decreased expression of glucose and peptide transporters in rat remnant kidney.
AB  - The loss of renal mass induces tubular hypertrophy as well as glomerular
      sclerosis and results in the end stage of renal disease. However, there is little
      information about adaptation of tubular glucose and peptide reabsorption under
      conditions of chronic renal failure. In the present study, we performed
      functional and molecular analyses focused on the tubular reabsorption of filtered
      glucose and small peptides using 5/6 nephrectomized rats at 16 weeks, as a model
      of chronic renal failure. Sixteen weeks after 5/6 nephrectomy or sham treatment,
      the brush-border membranes and total RNA were obtained from the renal cortex to
      evaluate the uptake of Na(+) gradient-dependent D-glucose and H(+) gradient
      dependent glycylsarcosine. The amounts of SGLT and PEPT mRNA levels were
      quantified by competitive PCR. The urinary glucose/creatinine ratio was markedly
      higher in nephrectomized rats than in sham-operated controls. Na(+)-dependent
      glucose uptake by the isolated renal brush-border membrane vesicles was markedly
      decreased in nephrectomized rats compared with that in sham-operated controls.
      However, H(+)-dependent peptide transport, another secondary active transport
      system in the brush-border membranes, was maintained. In addition, kinetic
      analysis revealed that both SGLT1 (high-affinity type)- and SGLT2 (low-affinity
      type)-mediated Na(+)/glucose uptake had markedly decreased Vmax values, but not
      Km values. Furthermore, competitive PCR demonstrated that the mRNA expression
      levels of SGLT2, PEPT1 and PEPT2, but not SGLT1, were markedly depressed. These
      findings suggested that loss of SGLT2 during chronic renal failure implies a high
      risk of renal glucosuria.

PMID- 15499169
TI  - Transepithelial permeation of tolbutamide across the human intestinal cell line,
      Caco-2.
AB  - Sulfonylurea hypoglycemic agents have interindividual variability in the
      gastrointestinal absorption rate. However, the absorption mechanism at the
      intestinal epithelium has not yet been clarified. To elucidate contribution of
      the specific mechanism for transepithelial transport of sulfonylureas, the apical
      to-basolateral and basolateral-to-apical transport studies of tolbutamide were
      carried out using Caco-2 cell monolayers cultured on the polycarbonate membrane.
      The transported amounts of the substrate were measured by HPLC to estimate the
      apparent permeability coefficients (P(app)). In the apical-to-basolateral flux,
      the transport activity of tolbutamide was facilitated when the pH of the apical
      medium was more acidic than the basolateral one. ATP-depletion decreased the
      P(app) of tolbutamide. The kinetic analysis of the permeation rate indicated that
      the saturable process largely contributed to the tolbutamide flux. The P(app) of
      tolbutamide was lowered by an ionophore and monocarboxylic acids, while
      dicarboxylic acids and the inhibitor for the anion exchanger had no effect. In
      addition, mutual inhibition with benzoic acid was observed in transepithelial
      transport of tolbutamide. On the other hand, the permeation rate of tolbutamide
      from the basolateral to apical side was concentration-independent and neither
      affected by metabolic inhibitors, probenecid nor inhibitors for P-glycoprotein.
      In conclusion, these results suggest that apical-to-basolateral transport of
      tolbutamide across the Caco-2 cell monolayers is mediated by the pH-dependent
      specific system, presumably shared with other organic anions such as benzoic
      acid.

PMID- 15499170
TI  - Utility of microtiter plate assays for human cytochrome P450 inhibition studies
      in drug discovery: application of simple method for detecting quasi-irreversible
      and irreversible inhibitors.
AB  - In this study, a simple in vitro method for detecting human P450 (CYP) quasi
      irreversible and irreversible inhibitors was evaluated. For the method, cDNA
      expressed CYPs were applied to microtiter plate assays, CYP inhibitors were co
      incubated with fluorometric substrates, and IC(50) were continuously measured
      (without stopping enzyme reactions). The typical reversible inhibitors
      (sulfaphenazole, tranylcypromine, quinidine, ketoconazole) showed constant IC(50)
      throughout the reaction. In contrast, the typical quasi-irrversible inhibitors
      (isosafrole, erythromycin, troleandomycin, diltiazem) and the typical
      irreversible inhibitors (furafylline, propranolol, mifepristone) showed time
      dependent decreases in IC(50). For CYP3A4 inhibition studies, two substrates, 7
      benzyloxyresorufin (BzRes) and 7-benzyloxy-4-trifluoromethyl-coumarin (BFC), were
      used. The IC(50) of the CYP3A4 inhibitors were dependent on the substrate.
      However, the quasi-irreversible and irreversible inhibitors could be detected by
      examining changes in the IC(50), regardless of the substrate. Further, the
      detection method was applied to josamycin and bergamottin. Josamycin did not show
      definite time-dependent decreases in IC(50) for CYP 3A4, suggesting that
      josamycin is neither a quasi-irrversible nor an irreversible inhibitor of CYP3A4.
      On the other hand, bergamottin showed time-dependent decreases in IC(50) for
      CYP1A2, CYP 2C9, CYP 2C19, CYP 2D6 and CYP 3A4, suggesting that bergamottin is a
      quasi-irrversible or an irreversible inhibitor of the 5 CYP isoforms. This method
      provides more rapid and reliable detection of quasi-irreversible and irreversible
      inhibitors and may be useful in drug discovery.

PMID- 15499171
TI  - The effects of emulsifying agents on disposition of lipid-soluble drugs included
      in fat emulsion.
AB  - The uses for drug delivery systems of two soybean oil fat emulsions prepared with
      an emulsifying agent, phosphatidyl choline (PC) or Pluronic F-127 (PLU), were
      examined comparatively in vivo and in vitro. In the presence of lipoprotein
      lipase (LPL) in vitro, the mean particle size of the PLU emulsion changed less
      than that of the PC emulsion. The production of non-esterified fatty acid (NEFA)
      from the PLU emulsion in the presence of LPL was smaller than that from the PC
      emulsion. These in vitro results indicate that the PLU emulsion is more stable
      than the PC emulsion. Plasma NEFA concentration following intravenous
      administration of the emulsions decreased with time for the PC emulsion, but was
      kept lower and constant for the PLU emulsion, supporting the in vitro stability
      data. The order of plasma cyclosporine A (CsA) concentration following
      intravenous administration in the above two emulsions and the mixed solution of
      polyethylene glycol 400 (PEG) and dimethylamide (DMA) in rats was PLU emulsion>PC
      emulsion>PEG/DMA solution. The plasma concentration was maintained higher and
      tissue distribution lower for the PLU emulsion than for other formulations. The
      uptake of oil violet (OV) into the rat parenchymal cells from the PLU emulsion
      was approximately half that from the PC emulsion, but the uptake into the Kupffer
      cells was almost equal in both emulsions. In conclusion, these emulsifying agents
      can control plasma elimination and tissue distribution of lipophilic drugs
      included in the emulsion. The use of the emulsion formulation makes it possible
      to avoid side effects through the reduction of drug uptake into non-targeted
      tissues.

PMID- 15499172
TI  - Protective effect of inactive ingredients against nephrotoxicity of vancomycin
      hydrochloride in rats.
AB  - A generic form of vancomycin for I.V. infusion (MEEK) is more soluble and stable
      than the brand-name form of vancomycin hydrochloride (VCM) due to the addition of
      two inactive ingredients: D-mannitol and Macrogol400 (PEG400). The aim of the
      present study was to compare the nephrotoxicity of MEEK with that of brand-name
      VCM (S-VCM) and to analyze the pharmacokinetics of these preparations. Following
      administration to rats at the clinical dose of 40 mg/kg, there was no difference
      between MEEK and S-VCM with regard to pharmacokinetics and effects on the
      kidneys, indicating that MEEK should be as effective as S-VCM. When administered
      at the nephrotoxic dose of 400 mg/kg, S-VCM caused impairment of renal function
      and kidney damage, and an increase of the plasma concentration due to decreased
      renal clearance was observed. In contrast, MEEK had virtually no effect on renal
      function or the kidneys and did not cause a marked change of renal clearance.
      These findings suggest that the inactive ingredients in MEEK play a role in
      reducing the nephrotoxicity of VCM.

PMID- 15499173
TI  - Proapoptotic effect of a dietary supplement: water soluble chitosan activates
      caspase-8 and modulating death receptor expression.
AB  - The effect of water-soluble chitosan, a natural polymer used as a dietary
      supplement, on human bladder-tumor cells was investigated. Apoptotic
      morphological change was demonstrated by nuclear staining. Chitosan-treated cells
      showed elevation of caspase-8-like activity, but no significant elevation of
      caspase-9-like activity, which suggest that proapoptotic effect of chitosan is
      attributable to death receptor activation and not to activation of the
      mitochondria-cytochrome c pathway. Chitosan increased expression of TNF-R1, but
      decreased Fas expression. Use of monoclonal antibodies to inhibit death-receptor
      signal transduction did not attenuate the proapoptotic activity of chitosan.
      Examination of death-ligands revealed that TNFalpha mRNA expression was markedly
      increased by chitosan treatment while FasL mRNA was not affected. Although the
      direct interaction of chitosan with death receptors remains unidentified, the
      results suggest that its proapoptotic effect might be related to interaction with
      TNFalpha or TNF-R1.

PMID- 15499174
TI  - Ethnic differences in genetic polymorphisms of CYP2D6, CYP2C19, CYP3As and
      MDR1/ABCB1.
AB  - Metabolic capacities for debrisoquin, sparteine, mephenytoin, nifedipine, and
      midazolam, which are substrates of polymorphic CYP2D6, CYP2C19, and CYP3A, have
      been reported to exhibit, in many cases, remarkable interindividual and ethnic
      differences. These ethnic differences are partly associated with genetic
      differences. In the case of the drug transporter ABCB1/MDR1, interindividual
      differences in its transporter activities toward various clinical drugs are also
      attributed to several ABCB1/MDR1 genetic polymorphisms. In this review, the
      existence and frequency of various low-activity alleles of drug metabolizing
      enzymes as well as populational drug metabolic capacities are compared among
      several different races or ethnicities. Distribution of nonsynonymous ABCB1/MDR1
      SNPs and haplotype frequency in various races are summarized, with the
      association of nonsynonymous SNPs with large functional alterations as a rare
      event.

PMID- 15499175
TI  - Effect of neonatal exposure of 17beta-estradiol and tamoxifen on hepatic CYP3A
      activity at developmental periods in rats.
AB  - We evaluated hepatic CYP3A activity during development in male and female rats
      and the effect of neonatal exposure of 17beta-estradiol and tamoxifen. In
      untreated and olive oil-treated (control) rats, hepatic CYP3A activities
      evaluated by erythromycin metabolism in vitro increased several-fold from age 2
      to 9 weeks in males. In contrast, activity in females remained at a low and
      constant level from 2 to 15 weeks. Exposure of 17beta-estradiol to neonates at a
      dose of 10 micromol/kg daily for 3 days on day 1-3 (approximately) or 4-6
      (approximately) after birth significantly increased hepatic CYP3A activity during
      the developmental period in both males and females, and a greater influence was
      observed in females exposed during days 4-6 (approximately). Pubertal exposure of
      17beta-estradiol (7-weeks old, 10 micromol/kg daily for 3 days) also increased
      hepatic CYP3A activity, but only in females. Neonatal exposure to tamoxifen (10
      micromol/kg daily for 3 days) showed no appreciable effect in either males or
      females. In conclusion, a marked sex-difference was observed in hepatic CYP3A
      activity, and exposure of 17beta-estradiol to neonates increased hepatic CYP3A
      activity during the developmental period, especially in female rats.

PMID- 15499176
TI  - Differences in transactivation between rat CYP3A1 and human CYP3A4 genes by human
      pregnane X receptor.
AB  - In an assay system using a human CYP3A4 reporter constructed with the promoter
      (+11 nt to -362 nt) and enhancer (-7.2 knt to -7.8 knt) regions including everted
      repeat separated by six nucleotides (ER-6) and direct repeat separated by three
      nucleotides (DR-3) motifs, the CYP3A4 transactivation was detected without
      overexpression of any nuclear receptors in rifampicin-treated HepG2 cells.
      Overexpression of human pregnane X receptor (hPXR) enhanced the transactivation.
      Rat CYP3A1 reporter constructed with the promoter region (+31 nt to -171 nt)
      including both DR-3 and ER-6 motifs was, however, not transactivated in
      rifampicin-treated cells, even after overexpression of hPXR. Although
      overexpression of retinoid X receptor alpha (RXRalpha) had no clear effect for
      both CYP3A reporters, co-expression of apolipoprotein AI regulatory protein-1
      (ARP-1) with hPXR resulted in the rifampicin-induced transactivation of the
      CYP3A1 reporter. A truncated CYP3A4 reporter retaining the both motifs showed the
      rifampicin-induced transactivation by overexpression of hPXR and ARP-1, while the
      transactivation in hPXR-overexpressed cells was not observed. These results
      support the idea that a nuclear receptor other than RXRalpha may play a role in
      the CYP3A transactivation together with hPXR. The present study also suggests the
      involvement of a novel cis-element in the hPXR-mediated CYP3A4 transactivation.

PMID- 15499177
TI  - Human CYP4B1 gene in the japanese population analyzed by denaturing HPLC.
AB  - Human CYP4B1 is a CYP4 enzyme with activity towards xenobiotics. Five alleles of
      human CYP4B1 have been identified in French Caucasians, but allelic variants of
      enzyme have not been determined in the Japanese population. To establish a rapid
      and sensitive means of detecting variant CYP4B1 alleles, we analyzed those of 192
      Japanese individuals using denaturing HPLC (DHPLC). We then determined the
      optimal conditions required to detect SNPs for each PCR fragment. Analysis by
      DHPLC revealed the novel alleles, CYP4B1(*)6 (517C>T and 1033G>A) and CYP4B1(*)7
      (AT881-882-del, 993G>A, and 1018C>T), as well as 3 known alleles. The frequencies
      of the CYP4B1(*)1, (*)2, (*)3, (*)4, (*)5, (*)6, and (*)7 alleles in 192 Japanese
      individuals were 0.490, 0.328, 0.154, 0, 0.016, 0.008, and 0.005, respectively.
      The allele frequencies among Japanese relative to those in French Caucasians for
      CYP4B1(*)1 (0.490 vs. 0.724) and CYP4B1(*)2 (0.328 vs. 0.147) significantly
      differed. Our results suggest that high throughput DHPLC can rapidly detect
      pharmacologically important variants in CYP genes.

PMID- 15499178
TI  - CYP3A5 Contributes significantly to CYP3A-mediated drug oxidations in liver
      microsomes from Japanese subjects.
AB  - The purpose of this study was to evaluate a contribution of polymorphic
      cytochrome P450 (CYP) 3A5 to the oxidation of diltiazem, midazolam and
      testosterone by liver microsomes from Japanese subjects. Twenty-seven liver
      samples were classified into three groups according to the CYP3A5 genotypes;
      CYP3A5(*)1/(*)1 (n=3), (*)1/(*)3 (n=12) and (*)3/(*)3 (n=12). The results of
      genotyping and immunochemical quantitation of CYP3A5 protein showed a good
      accordance between the CYP3A5 genotype and CYP3A5 content but not CYP3A4 content
      in liver microsomes. The expression levels of hepatic CYP3A5 protein ranged from
      20 to 60% of the sum of CYP3A4 and CYP3A5 contents in subjects with at least one
      wild type allele ((*)1). The CYP3A5 contents correlated well with liver
      microsomal activities of diltiazem N-demethylation, midazolam 1'- and 4
      hydroxylations and testosterone 6beta-hydroxylation among subjects carrying at
      least one (*)1 allele. In addition, the correlation coefficients of CYP3A5
      contents with the rates of diltiazem N-demethylation, midazolam 1'-hydroxylation
      and testosterone 6beta- hydroxylation were higher than those of CYP3A4, although
      the value of CYP3A5 with the midazolam 4-hydroxylation rate was similar to that
      of CYP3A4. Kinetic analyses revealed a biphasic diltiazem N-demethylation in
      liver microsomes from subjects carrying the (*)1 allele. The apparent V(max)/K(m)
      values for recombinant CYP3A5 indicated the greater contributions to diltiazem N
      demethylation and midazolam 1'-hydroxylation as compared with CYP3A4. These
      results suggest that polymorphic CYP3A5 contributes markedly to the drug
      oxidations, particularly diltiazem N-demethylation, midazolam 1'- hydroxylation
      and testosterone 6beta-hydroxylation by liver microsomes from Japanese subjects.

PMID- 15499179
TI  - Factors affecting glucuronidation activity in Caco-2 cells.
AB  - Presystemic intestinal metabolism reduces the intestinal absorption and
      bioavailability of orally administered drugs. The factors affecting
      glucuronidation activity in Caco-2 cells seeded in Transwell (4.7 cm(2)) require
      clarification to establish an in-vitro system to assess intestinal
      glucuronidation metabolism for novel drug development. alpha-Naphthol (alpha-NA),
      a substrate for UGT1A6 in Caco-2 cells, has often been used as a model substrate
      for gluruonidation. alpha-Naphthol glucuronidation activity increased from 7 to
      21 culture days after seeding in Transwell and stabilized after 21 days. The
      higher the passage number of Caco-2 cells, the larger the variance of
      glucuronidation activity, but apical pH did not significantly influence
      glucuronidation in the pH range of 5.5 to 7.4. When the passage number ranged
      from 83 to 159, Km,app was highest at passage number 130. In contrast, Vmax,app
      increased with the passage number. This indicates that the kinetic parameters for
      glucuronidation in Caco-2 cells are dependent on the passage number of the cells.
      These results should be useful for establishing the experimental conditions for
      Caco-2 cells that predict intestinal glucuronidation activity in vivo.

PMID- 15499180
TI  - Tissue-specific mRNA expression profiles of human nuclear receptor subfamilies.
AB  - Pairs of forward and reverse primers and TaqMan probes specific to each human
      nuclear receptor were prepared. Analysis of the mRNA expression level of each
      target of 43 nuclear receptors in total RNA from single and pooled specimens of
      various human organs (liver, kidney, adrenal gland, lung, heart, brain,
      cerebellum, skeletal muscle, spleen, thymus, thyroid gland, prostate, testis,
      uterus, placenta, bone marrow, trachea, and salivary gland) was performed by real
      time reverse transcription PCR using an ABI PRISM 7700 sequence detector system.
      The mRNA expression of 33 nuclear receptors (NR1A1, 1A2, 1B1, 1B2, 1B3, 1C1, 1C2,
      1C3, 1D1, 1D2, 1F1, 1F2, 1F3, 1H2, 1H3, 1I1, 1I2, 2B1, 2B2, 2B3, 2C1, 2C2, 2F1,
      2F2, 3A2, 3B1, 3C1, 3C2, 3C4, 4A1, 4A2, 4A3, and 6A1) was successfully detected
      in all of the tissues by this method. NR1H4, 2A1, and 3C3 mRNAs were not
      detectable in the heart, heart, and liver, respectively. NR5A2 mRNA was not
      detectable in either the brain or cerebellum. NR3A1 mRNA was not detectable in
      the small intestine, colon, brain, and cerebellum. NR5A1 mRNA was not detectable
      in the kidney, stomach, small intestine, and colon. NR1I3 mRNA was detected in
      the liver, kidney, stomach, small intestine, adrenal gland, lung, brain, skeletal
      muscle, thymus, thyroid gland, prostate, testis, placenta, and trachea. NR2A2
      mRNA was detected in the liver, kidney, prostate, testis, uterus, and trachea.
      NR2E1 mRNA was detected in the adrenal gland, brain, cerebellum, testis,
      placenta, and bone marrow. NR2E3 mRNA was detected in the adrenal gland, thyroid
      gland, prostate, testis, uterus, trachea, and salivary gland. This study provides
      information concerning the tissue distribution of the mRNA expression of 43 human
      nuclear receptors. The mRNA expression profiles of CYP3A4, CYP3A5 and ABC
      transporters are also shown. These results are valuable for establishing a
      nuclear receptor-mediated screening system for new chemical entities in new drug
      development.

PMID- 15499181
TI  - Comparison of the disposition behavior of organic anions in an animal model for
      Wilson's disease (Long-Evans Cinnamon rats) with that in normal Long-Evans Agouti
      rats.
AB  - Long-Evans Cinnamon (LEC) rats have an abnormality similar to that observed in
      Wilson's disease in humans and are therefore a good animal model for the study of
      Wilson's disease. LEC rats develop hereditary hepatitis and severe jaundice.
      Mutant animals with hyperbilirubinemia have been widely used as animal models for
      human diseases. Among these mutant animals, Eisai hyperbilirubinemic rats (EHBR)
      have defective biliary excretion of organic anions. Thus, biliary excretion of
      sulfobromophthalein (BSP) and urinary excretion of phenolsulfonphthalein (PSP) in
      LEC rats were compared with those in Long-Evans Agouti (LEA) rats. In LEC rats,
      the excretion of BSP, a multidrug resistance-associated protein 2 (Mrp2/Abcc2)
      substrate, was significantly decreased compared to that in LEA rats. It has been
      reported that the transport function for organic anions on the kidney is
      maintained in EHBR. However, the urinary excretion of PSP is impaired in LEC
      rats. It is possible that organic anion transporters responsible for the urinary
      excretion of PSP in LEA rats and EHBR are impaired in LEC rats. It is important
      to elucidate the relationship between organic anion secretion and Wilson's
      disease.

PMID- 15499182
TI  - Three novel single nucleotide polymorphisms (SNPs) of the CYP2B6 gene in Japanese
      individuals.
AB  - We sequenced all exons and exon-intron junctions of the CYP2B6 gene from 200
      Japanese individuals. We found three novel single nucleotide polymorphisms (SNPs)
      (1375A>G, 1427G>A and 1454A>T) causing amino acid substitutions (Met(459)Val,
      Gly(476)Asp and Gln(485)Leu in exon 9), respectively. The detected SNP was as
      follows: 1) SNP, 031226Hiratsuka01; GENE NAME, CYP2B6; ACCESSION NUMBER,
      AC023172; LENGTH, 25 base; 5'-CAGAACTTCTCCA/GTGGCCAGCCCCG-3'. 2) SNP,
      031226Hiratsuka02; GENE NAME, CYP2B6; ACCESSION NUMBER, AC023172; LENGTH, 25
      base; 5'-CCCAGGAGTGTGG/ATGTGGGCAAAAT-3'. 3) SNP, 031226Hiratsuka03; GENE NAME,
      CYP2B6; ACCESSION NUMBER, AC023172; LENGTH, 25 base; 5'
      CCCCAACATACCA/TGATCCGCTTCCT-3'.

PMID- 15499183
TI  - Molecular aspects of renal handling of aminoglycosides and strategies for
      preventing the nephrotoxicity.
AB  - Aminoglycosides such as gentamicin and amikacin are the most commonly used
      antibiotics worldwide in the treatment of Gram-negative bacterial infections.
      However, serious complications like nephrotoxicity and ototoxicity are dose
      limiting factors in the use of aminoglycosides. A relatively large amount of the
      intravenously administered dose is accumulated in the kidney (about 10% of dose),
      whereas little distribution of aminoglycosides to other tissues is observed.
      Aminoglycosides are taken up in the epithelial cells of the renal proximal
      tubules and stay there for a long time, resulting in nephrotoxicity. Acidic
      phospholipids are considered as a binding site for aminoglycosides in the brush
      border membrane of the proximal tubular cells. More recently, it has been
      reported that megalin, a giant endocytic receptor abundantly expressed at the
      apical membrane of renal proximal tubules, plays an important role in binding and
      endocytosis of aminoglycosides in the proximal tubular cells. The elucidation of
      the aminoglycoside-binding receptor would help design a strategy to prevent
      against aminoglycoside-induced nephrotoxicity. In this review, we summarize
      recent advances in the understandings of the molecular mechanisms responsible for
      renal accumulation of aminoglycosides, especially megalin-mediated endocytosis.
      In addition, approaches toward prevention of aminoglycoside-induced
      nephrotoxicity are discussed, based on the molecular mechanisms of the renal
      accumulation of aminoglycosides.

PMID- 15499184
TI  - The organic anion transporter (OATP) family.
AB  - In the last decade, many organic anion transporters have been isolated,
      characterized their distribution and substrates. The recently identified organic
      anion transporter family OATP (organic anion transporting polypeptide)/LST (liver
      specific transporter) family, transport bile acids, hormones as well as
      eicosanoids, various compounds (BSP, HMG-CoA reductase inhibitor, angiotensin
      converting enzyme inhibitor, etc.). The isolation of the family revealed that not
      only hydrophilic compounds, drugs and hormones of lipophilic nature need a
      membrane transport system to penetrate cell membrane. In this family, the
      nomenclature becomes very complicated and the physiological role of this family
      is still unclear except about few organs such as the brain, liver and kidney.
      Even in such organs, the co-existence of the OATP/LST family and similar
      substrate specificity hamper the progress and clear characterization identifying
      the real role of the transporter family. Here, recent progress and an insight of
      this field are reviewed.

PMID- 15499185
TI  - Functional regions of organic cation/carnitine transporter OCTN2 (SLC22A5): roles
      in carnitine recognition.
AB  - The organic cation/carnitine transporter OCTN2 transports carnitine in a sodium
      dependent manner, whereas it transports organic cations sodium-independently. To
      elucidate the functional domain in OCTN2, we constructed chimeric proteins of
      human OCTN2 (hOCTN2) and mouse OCTN3 (mOCTN3) and introduced mutations at several
      amino acids conserved among human, rat and mouse OCTN2. We found that
      transmembrane domains (TMD) 1-7 are responsible for organic cation transport and
      for sodium dependence in carnitine transport. Within TMD1-7, Q180 and Q207 of
      hOCTN2 are the critical amino acids for the sodium dependence, and double
      mutation of Q180 and Q207 resulted in minimal change in transport activity when
      sodium was removed from the uptake medium. We propose that sodium-dependent
      affinity for carnitine is dependent on sodium recognition by these critical amino
      acids in hOCTN2, whereas carnitine transport by OCTN2 requires functional linkage
      between TMD1-7 and TMD11.

PMID- 15499186
TI  - Effect of experimental acute renal and hepatic failure on absorption of
      tacrolimus in rat small intestine.
AB  - The objective of this study is to evaluate the effect of acute renal or hepatic
      failure on the intestinal absorption of tacrolimus. Simultaneous perfusion study
      in rat small intestine revealed that the extent of absorption into blood vessels
      was decreased in the jejunum and the ileum of rat of acute renal failure due to
      the decrease in the uptake of tacrolimus into enterocytes. In contrast, there
      observed no significant changes in tacrolimus absorption in rat of acute hepatic
      failure. Since it has been reported that tacrolimus absorption is regulated
      mainly by Cytochrome P-450 (CYP) mediated metabolism in the jejunum, but by P
      glycoprotein (P-gp) mediated efflux in the ileum, these factors might contribute
      to the changes in intestinal absorption of tacrolimus in rat of acute renal
      failure. Enzyme inhibitor, ketoconazole, was co-perfused with tacrolimus to
      specify the effect of CYP and P-gp. However, since ketoconazole failed to recover
      the permeability in the jejunum and ileum of rat of acute renal failure, it is
      considered that the changes in CYP or P-gp functions might not be involved in the
      decreased uptake of tacrolimus. This type of kinetic study in rats should be
      valuable to identify the precise mechanisms of drug absorption and the effects of
      various diseases on it, such as acute renal or hepatic failure.

PMID- 15499187
TI  - Regulation of drug absorption from small intestine by enteric nervous system I: a
      poorly absorbable drug via passive diffusion.
AB  - To investigate the regulation of drug absorption from the small intestine by the
      enteric nervous system (ENS), the vascular-luminal perfusion study and the in
      vitro transport study were performed by employing phenol red as a poorly
      absorbable model compound. The effect of ENS on the intestinal absorption of
      phenol red was examined by adding epinephrine, an adrenergic agonist, or
      bethanechol, a cholinergic agonist into the vascular perfusate in the vascular
      luminal perfused rat small-intestine preparation. The viability of the perfused
      intestine was checked by the recovery of the vascular perfusate, net water flux
      and absorbability of antipyrine, a well absorbable drug, and it was confirmed
      that the function of the perfused small-intestine preparation was maintained for
      at least 1 hr. The effect of epinephrine or bethanechol on the function of the
      small intestine was recognized as the increase in net water absorption, or the
      promotion of the water secretion, respectively. These phenomena are ones that are
      typically observed when adrenergic or cholinergic neuron is stimulated. Then, we
      investigated the small-intestinal absorption of phenol red in the vascular
      luminal perfused preparation. Absorption clearance (CL(abs)) of phenol red was
      gradually increasing during the perfusion for 1 hr, but the 20-min vascular
      perfusion with the perfusate containing epinephrine made CL(abs) of phenol red
      constant and significantly lower than those for control study. Furthermore, after
      the perfusate was changed with the one without any agonist, again, CL(abs) of
      phenol red started to increase. These results clearly indicate that the
      stimulation of adrenergic neuron by epinephrine leads to the decrease in the
      small-intestinal absorption of phenol red. On the other hand, the vascular
      perfusion of bethanechol resulted in the increase in CL(abs) of phenol red
      comparing to the control study. Removing bethanechol from the vascular perfusate
      decreased CL(abs) of phenol red, again. The in-vitro transport study using the
      isolated jejunum sheet also showed that epinephrine in the serosal solution
      significantly decreased the transport of phenol red, which can be ascribed to the
      paracellular pathway tightened by the action of epinephrine because of the
      increase in transmucosal electrical resistance (TER). On the other hand, although
      the effect of bethanechol on both the transport of phenol red and TER was not
      statistically significant, the transport of phenol red tended to increase and the
      values of TER are smaller than those of control study.

PMID- 15499188
TI  - Pharmacokinetic modeling of species-dependent enhanced bioavailability of
      trifluorothymidine by thymidine phosphorylase inhibitor.
AB  - TAS-102, a new oral drug, is composed of an antitumor drug, alpha,alpha,alpha
      trifluorothymidine (FTD), and its metabolic inhibitor, 5-chloro-6-(2
      iminopyrrolidine-1-yl)methyl-2,4(1H,3H)-pyrimidinedione hydrochloride (TPI). It
      has been reported that the oral administration of TAS-102 increases the AUC of
      FTD in rodents and monkeys in different manners. In this study, a pharmacokinetic
      model was developed, in an attempt to evaluate the bioavailability of FTD in
      these animals after the co-administration of TPI. Since TPI inhibits FTD
      metabolism competitively, a time-dependent as well as concentration-dependent
      model for the hepatic intrinsic clearance of FTD was developed including the time
      courses of both FTD and TPI. Based on this modeling, we were able to
      quantitatively explain the TPI dose-dependent enhancement of AUC of FTD in
      monkeys, while little increase was observed in rats. These results are consistent
      to observations that thymidine phosphorylase (TPase) is predominantly expressed
      in monkeys; while uridine phosphorylase (UPase) is superior to TPase in rats.
      Since TPase is also predominantly expressed in humans, the pharmacokinetic model
      developed in this study can be used to explain the bioavailability of TAS-102 in
      humans.

PMID- 15499189
TI  - Regioselective monosulfation and disulfation of the phytoestrogens daidzein and
      genistein by human liver sulfotransferases.
AB  - Regioselective sulfation of the phytoestrogens daidzein (DZ, 7,4'
      dihydroxyisoflavone) and genistein (GS, 5,7,4'-trihydroxyisoflavone) was
      investigated using human liver cytosol and purified recombinant human
      sulfotransferase (SULT) isoforms, SULT1A1, SULT1A3, SULT2A1, and SULT1E1. 7
      Position-preferential sulfation of DZ and GS was observed in human hepatic
      cytosols from 3 male and 3 female subjects. Average ratios for 7- to 4'-sulfate
      formation were 4.5:1 from DZ and 8.4:1 from GS in these human liver cytosols.
      Apparent K(m) values for the 7- and 4'-sulfation of DZ and GS by these cytosols
      were similar and in a range from 0.46 to 0.66 microM. All recombinant human SULTs
      had activity for 7- and 4'-sulfation of these phytoestrogens except for 7
      sulfating activity of SULT1A3. SULT1A1 and SULT1E1 exhibited much higher
      catalytic efficiency, k(cat)/K(m), for 7- and 4'-sulfation of these substrates
      than did the other two, SULT1A3 and SULT2A1. SULT1A1 showed K(m) values of 0.47
      and 0.52 microM for the mono-sulfation of DZ and GS, respectively, which were
      very similar to those of human cytosol. The observed k(cat)/K(m) indicated that
      SULT1A1 catalyzed 7-sulfation of DZ and GS at rates 4.4- and 8.8-fold higher,
      respectively, than such 4'-sulfation. However, with SULT1E1, catalytic efficiency
      was very similar for the sulfation of both positions. These data strongly suggest
      that SULT1A1 plays a major role in monosulfation of the phytoestrogens and
      determines the regioselectivity of sulfation in human hepatic cytosol. A kinetic
      study for 7,4'-disulfate formation of DZ and GS from their 7- and 4'-monosulfates
      indicated that SULT1E1 most efficiently catalyzed both reactions among human
      SULTs.

PMID- 15499190
TI  - Evaluation of fast disintegrating lansoprazole tablet in human subjects.
AB  - Fast disintegrating lansoprazole tablet (LFDT) has been developed as a multiple
      unit formulation and evaluated using human subjects as compared to the
      conventional lansoprazole (LPZ) capsule containing enteric coated granules.
      Twelve healthy male volunteers, who were confirmed as extensive metabolizers
      (EMs) based on the plasma levels of LPZ sulphone metabolite, were enrolled into
      the study and genotype of CYP2C19 was confirmed. They kept 30 mg LFDT in their
      mouths for 2 min and the saliva was recovered without swallow. Eight subjects did
      not show LPZ in their serum after intake. Although LPZ was detected in 4
      subjects' serum, their concentrations were less than 5 ng/mL. LPZ was thought to
      be not absorbed from the oral cavity. LFDT was orally administered to 12 healthy
      male EMs at two doses, 15 mg and 30 mg, and serum LPZ concentrations were
      measured. The mean C(max) and AUC(0-24) were 474.1+/-254.0 ng/mL and 1105.3+/
      1101.4 ng.h/mL (15 mg) and 992.8+/-384.3 ng/mL and 2216.5+/-1270.1 ng.h/mL (30
      mg). By comparing to that obtained after oral administration of the same doses of
      LPZ capsule, serum LPZ concentration vs. time curve was almost the same level,
      i.e., C(max) and AUC(0-24) did not have significant differences. From these
      results, LFDT has been shown to be equivalent to LPZ capsule and will show the
      same acid suppressing effects in the clinical situation.

PMID- 15499191
TI  - A novel single nucleotide polymorphism (SNP) of the CYP2C19 gene in a Japanese
      subject with lowered capacity of mephobarbital 4'-hydroxylation.
AB  - We sequenced all nine exons and exon-intron junctions of the cytochrome P450 2C19
      (CYP2C19) gene from a Japanese subject with a lowered capacity of CYP2C19
      mediated 4'-hydroxylation after an oral administration of mephobarbital. We found
      a novel single nucleotide polymorphism (SNP) of CYP2C19 gene as follows: SNP,
      040110MoritaJ001; GENENAME: CYP2C19; ACCESSION NUMBER: NT_030059.8; LENGTH; 25
      bases; 5'-GAGGGCCTGGCCC/TGCATGGAGCTGT-3'. The SNP (168946C>T) induced an amino
      acid alteration (Arg442Cys) located in exon 9 close to the heme-binding region of
      CYP2C19, which may result in the decrease in the catalytic properties of CYP2C19.
      A new allele having this SNP was designated as CYP2C19*16.

PMID- 15499193
TI  - Cancer prevention by natural compounds.
AB  - Increasing attention is being paid to the possibility of applying cancer
      chemopreventive agents for individuals at high risk of neoplastic development.
      For this purpose by natural compounds have practical advantages with regard to
      availability, suitability for oral application, regulatory approval and
      mechanisms of action. Candidate substances such as phytochemicals present in
      foods and their derivatives have been identified by a combination of
      epidemiological and experimental studies. Plant constituents include vitamin
      derivatives, phenolic and flavonoid agents, organic sulfur compounds,
      isothiocyanates, curcumins, fatty acids and d-limonene. Examples of compounds
      from animals are unsaturated fatty acids and lactoferrin. Recent studies have
      indicated that mechanisms underlying chemopreventive potential may be
      combinations of anti-oxidant, anti-inflammatory, immune-enhancing, and anti
      hormone effects, with modification of drug-metabolizing enzymes, influence on the
      cell cycle and cell differentiation, induction of apoptosis and suppression of
      proliferation and angiogenesis playing roles in the initiation and secondary
      modification stages of neoplastic development. Accordingly, natural agents are
      advantageous for application to humans because of their combined mild mechanism.
      Here we review naturally occurring compounds useful for cancer chemprevention
      based on in vivo studies with reference to their structures, sources and
      mechanisms of action.

PMID- 15499192
TI  - Fourteen novel single nucleotide polymorphisms in the SLC22A2 gene encoding human
      organic cation transporter (OCT2).
AB  - Thirty-three genetic variations including fourteen novel ones were found in the
      SLC22A2 gene from 116 Japanese individuals. The novel variations were as follows:
      596C>T (MPJ6_OC2003), 602C>T (MPJ6_OC2004), IVS5+20A>G (MPJ6_OC2010), IVS5-84_
      83insG (MPJ6_OC2013), IVS6+30T>C (MPJ6_OC2014), IVS6+146G>T (MPJ6_OC2016),
      IVS6+179G>T (MPJ6_OC2017), IVS6-16delT (MPJ6_OC2018), 1920G>A (MPJ6_OC2022),
      2153G>A (MPJ6_OC2026), 2157C>T (MPJ6_OC2028), 2306T>C (MPJ6_OC2031), 2342+5T>C
      (the last nucleotide number of mRNA+the position in the 3'-flanking region;
      MPJ6_OC2032) and 2342+127T>C (MPJ6_OC2033). Six variations were located in the
      exons, four of which were in the 3'-untranslated region (3'-UTR) of exon 11; six
      were in the introns; and two were in the 3'-flanking region. The frequencies were
      0.802 for IVS5-84_-83insG, 0.013 for 602C>T, 0.009 for 596C>T, and 0.004 for the
      other 11 variations. Among them, 596C>T and 602C>T resulted in amino acid
      substitutions (Thr199Ile and Thr201Met, respectively).

PMID- 15499194
TI  - Transporter mRNA expression in a conditionally immortalized rat small intestine
      epithelial cell line (TR-SIE).
AB  - Small intestine epithelial cell lines (TR-SIE), which are established from the
      small intestine of transgenic rats harboring temperature-sensitive simian virus
      40 large T-antigen gene (tsA58 Tg rat), were used to characterize the mRNA
      expression of small intestine transporters. TR-SIE cells had a polygonal
      morphology and expressed cytokeratin protein and villin mRNA. Although the large
      T-antigen was strongly expressed at 33 degrees C, this was reduced at 37 and 39
      degrees C. Concomitantly, the cell growth was arrested at 37 and 39 degrees C
      compared with that at 33 degrees C, suggesting that TR-SIE cells are
      conditionally immortalized cell lines. RT-PCR analysis revealed that TR-SIE cells
      expressed ABCB1 (mdr1a and mdr1b), ABCB4 (mdr2), ABCC2 (mrp2), ABCC6 (mrp6),
      ABCG1, ABCG2 (bcrp/mxr), Slc21a7 (Oatp3), Slc15a1 (PepT1), and Slc16a1 (Mct1).
      Conditionally immortalized rat small intestine epithelial cell lines were
      established from tsA58 Tg rats and expressed the mRNA of intestinal transporters.

PMID- 15499195
TI  - Tolbutamide uptake via pH- and membrane-potential-dependent transport mechanism
      in mouse brain capillary endothelial cell line.
AB  - The purpose of this study was to investigate the transport mechanism of
      tolbutamide across the blood-brain barrier (BBB) using MBEC4 cells as an in vitro
      BBB model. METHODS: The BBB transport of tolbutamide was studied by using a mouse
      brain capillary endothelial cell line, MBEC4, cultured on dishes with their
      luminal membrane facing the culture medium. RESULTS: The uptake of
      [14C]tolbutamide by MBEC4 cells was dependent on temperature and energy. The
      uptake coefficient of [14C]tolbutamide increased markedly with decreasing pH of
      the external medium from neutral to acidic. Valinomycin and replacement of
      chloride with sulfate or gluconate significantly increased the initial uptake of
      [14C]tolbutamide, while replacement with nitrate significantly decreased it. The
      uptake was significantly reduced by a proton ionophore, FCCP, and an anion
      exchange inhibitor, DIDS. The initial uptake of [14C]tolbutamide was saturable
      with Kt of 0.61+/-0.03 mM (pH 7.4) and 1.76+/-0.19 mM (pH 6.5). At pH 6.5, the
      initial uptake of [14C]tolbutamide was significantly reduced by several sulfa
      drugs, salicylic acid, valproic acid and probenecid, and was competitively
      inhibited by sulfaphenazole (Ki=3.47+/-0.50 mM) and valproic acid (Ki=2.29+/-0.43
      mM). CONCLUSION: These observations indicate the existence of a pH- and membrane
      potential-dependent anion exchange and/or proton-cotransport system(s) for
      concentrative uptake of tolbutamide and sulfa drugs in MBEC4 cells.

PMID- 15499196
TI  - Effects of continuous ingestion of green tea or grape seed extracts on the
      pharmacokinetics of midazolam.
AB  - Limited systematic data on herb-drug interaction are available, despite many
      opportunities to concomitant use of herb with prescribed drugs. We investigated
      the effects of 15 herbal extracts in dietary supplements on CYP2C9, CYP2D6 and
      CYP3A4 activities in human liver microsomes. Strong inhibition of these CYP
      activities was found by the addition of green tea extracts (GTE) or grape seed
      extracts (GSE) in vitro. To examine the effects of these extracts on CYP3A
      activities in vivo, the pharmacokinetics of midazolam (MDZ) was analyzed in rats.
      Although single treatments with these extracts had negligible effects, 1 week of
      treatment with them resulted in a significant increase in the ke of intravenously
      administered MDZ, indicating the induction of CYP3A in the liver. In contrast, 1
      week of treatment with GTE, but not GSE, caused a significant increase in the
      C(max) and AUC(0-infinity) of orally administered MDZ without change in the
      t(1/2), suggesting a reduction in CYP3A activity in the small intestines. These
      studies indicate that subchronic ingestion of GTE or GSE may alter the
      pharmacokinetics of MDZ, and the effects of GTE on CYP3A activity appear opposite
      between liver and small intestine, which could not be predicted from in vitro
      experiments.

PMID- 15499197
TI  - Enhancement of acetaminophen cytotoxicity in selenium-binding protein
      overexpressed COS-1 cells.
AB  - The role of selenium-binding protein (SeBP), which has a high ability to
      associate with acetaminophen (AAP), on the cytotoxicity of AAP was studied. To
      clarify this issue, we examined the cytotoxic effect of AAP using COS cells
      stably expressing SeBP. Expression of SeBP enhanced the susceptibility of the
      cells to AAP-induced cytotoxicity. Several clones of SeBP-expressed COS cells
      were obtained, and they exhibited different degrees of susceptibility toward AAP.
      It was found that there is an inverse correlation between the expression level
      and the cell viability (r=-0.872). On the other hand, no increase in toxicity was
      observed in the SeBP-expressed cells treated with N-acetyl-p-quinone imine
      (NAPQI), which is an active metabolite of AAP. These results show that SeBP is an
      important factor in AAP hepatotoxicity. Moreover, our data suggest that the toxic
      mechanism of AAP differs from that of NAPQI.

PMID- 15499198
TI  - Kinetic studies of covalent binding between N-acetyl-L-cysteine and human serum
      albumin through a mixed-disulfide using an N-methylpyridinium polymer-based
      column.
AB  - The binding properties of the disulfide covalent bond between N-acetyl-L-cysteine
      (NAC) and human serum albumin (HSA) were investigated. HSA, purified from either
      healthy subjects or renal failure patients, was incubated with NAC in buffer and
      analyzed by 4VP-EG-Me column chromatography, which can distinguish between the
      redox states of the only free thiol of HSA. Although intact HSA was found to
      consist of mainly three sub-types, marcaptoalbumin (HMA), cysteine-bound
      nonmercaptoalbumin (HNA(Cys)) and a further oxidized form (HNA(oxy)), the
      formation of a new type of nonmercaptoalbumin (HNA(NAC)) was confirmed after
      incubation with NAC. Interestingly, NAC rapidly dissociated Cys from HNA(Cys) and
      NAC itself bound very slowly to HSA. These findings suggest that the interaction
      between NAC and HSA proceeds in a 2-step processes. The first-order binding and
      dissociation rate constants of NAC to healthy HSA (k(on,NAC)) and Cys from
      healthy HNA(Cys) (k(off,Cys)) were approximately 0.0032 and 1.3 (h(-1)),
      respectively. On the other hand, HSA from renal failure patients showed decreased
      HMA and increased HNA(Cys). The k(on,NAC) and k(off,Cys) were 0.0094 and 0.45 (h(
      1)), respectively, suggesting that the pathological state may affect the binding
      properties of HSA and NAC.

PMID- 15499199
TI  - Genotyping of single nucleotide polymorphisms (SNPs) influencing drug response by
      competitive allele-specific short oligonucleotide hybridization (CASSOH) with
      immunochromatographic strip.
AB  - Using competitive allele-specific oligonucleotide hybridization with
      immunochromatographic strip (CASSOH), we have developed a simplified method for
      the detection of eight polymorphisms that are especially important in the
      identification of drug responders or non-responders and patients at increased
      risk of drug toxicity. The genotyping method is unambiguously determined by the
      presence or the absence of visible purple lines on the immunochromatographic
      strip, and results are obtained within 5 min after PCR. This method is rapid,
      highly sensitive, simplified, and should be suitable for point-of-care genotyping
      in clinical settings.

PMID- 15499200
TI  - Seven novel single nucleotide polymorphisms in the human SLC22A1 gene encoding
      organic cation transporter 1 (OCT1).
AB  - Twenty genetic variations, including seven novel ones, were found in the human
      SLC22A1 gene, which encodes organic cation transporter 1, from 116 Japanese
      individuals. The novel variations were as follows: -94C>A in the 5'-untranslated
      region (A of the translation start codon is numbered +1 in the cDNA sequence;
      MPJ6_OC1001), 350C>T (MPJ6_OC1004), IVS1-35T>C (MPJ6_OC1006), 561G>A
      (MPJ6_OC1010), IVS6+75C>G (MPJ6_OC1014), IVS8+108A>G (MPJ6_OC1017), and
      1671_1673delATG (MPJ6_OC1020). The frequencies were 0.082 for IVS1-35T>C, 0.022
      for IVS6+75C>G, 0.009 for 561G>A, and 0.004 for the other 4 variations. Among
      them, 350C>T resulted in the amino acid substitution Pro117Leu, which is located
      in the large extracellular loop between transmembrane domains 1 and 2. Also, we
      detected the four previously reported nonsynonymous variations, 123C>G
      (Phe41Leu), 480C>G (Phe160Leu), 1022C>T (Pro341Leu), and 1222A>G (Met408Val) with
      frequencies of 0.004, 0.086, 0.168, and 0.810, respectively.

PMID- 15499201
TI  - Novel nonsynonymous single nucleotide polymorphisms in the CYP2D6 gene.
AB  - Cytochrome P450 (CYP) 2D6 is an important drug-metabolizing enzyme, and its gene
      is known to be highly polymorphic. Here, we report five novel nonsynonymous
      single nucleotide polymorphisms (SNPs), and 65 other sequence variations detected
      from the gene coding for cytochrome P450 (CYP) 2D6 in 254 Japanese subjects. Two
      of the novel nonsynonymous SNPs were associated with the *10 key SNP, C100T.
      Among the 65 variations, 23 were novel, including 12 SNPs in 5'-flanking, 1 in 5'
      untranslated, and 10 in intronic regions. The nonsynonymous SNPs in the CYP2D6
      gene were as follows: 73 C>T (Arg25Trp, exon 1), 972 C>T (Ala90Val, exon 2), 1611
      T>A (Phe120Ile, exon 3), 1720 A>C (Glu156Ala, exon 3), 3172 A>C (Glu334Ala, exon
      7). The SNPs, 73C>T, 972 C>T, 1611 T>A, 1720 A>C and 3172 A>C were linked with
      *10, *1, *10, *1 and *2, respectively.

PMID- 15499202
TI  - Genetic variations of the AHR gene encoding aryl hydrocarbon receptor in a
      Japanese population.
AB  - Aryl hydrocarbon receptor (AhR), encoded by the AHR gene, is a transcriptional
      factor that induces various drug metabolizing enzymes in response to diverse
      endogenous and exogenous ligands. In order to identify genetic variations of the
      AHR gene, genomic DNA from 242 Japanese individuals was sequenced. We identified
      32 single nucleotide variations, including 25 novel ones [7 were in the coding
      exons, 7 in the introns, 1 in the 5'-untranslated region (UTR), 5 in the 3'-UTR,
      2 in the 5'-flanking region, and 3 in the 3'-flanking region] and a GGGGC repeat
      polymorphism (a novel microsatellite marker) in the promoter region. The novel
      nonsynonymous variations were 50A>C (Lys17Thr), 1202A>G (Lys401Arg), 1459A>G
      (Asn487Asp), and 1541T>C (Ile514Thr). The allele frequencies were 0.010 for
      1459A>G (Asn487Asp) and 0.002 for the other 3 variations. Also detected in this
      analysis was the known nonsynonymous single nucleotide polymorphism 1661G>A
      (Arg554Lys) at a 0.444 frequency.

PMID- 15499203
TI  - Medical management of urinary stone disease.
AB  - A variety of dietary and metabolic factors may contribute or cause stone
      formation in idiopathic calcium oxalate nephrolithiasis. Dietary factors include
      a high intake of animal proteins, oxalate and sodium, and a low intake of fluids
      and potassium-containing citrus products. Some of the metabolic causes of stones
      are hypercalciuria, hypocitraturia, gouty diathesis, hyperoxaluria, and
      hyperuricosuria. Dietary modification, to be applied in all patients with stones
      includes a high fluid intake, restriction of oxalate and sodium, and balanced
      diet with animal proteins complemented by adequate intake of fruits and
      vegetables. When dietary modification is ineffective in controlling stone
      formation or in the presence of severe metabolic derangements, a pharmacologic
      intervention may be necessary. In a simple approach, thiazide or indapamide with
      potassium citrate is recommended for patients with hypercalciuria, and potassium
      citrate alone for the remaining normocalciuric subjects.

PMID- 15499204
TI  - Renal stone disease: the urological perspective.
AB  - Percutaneous nephrolithotomy, extracorporeal lithotripsy and ureteroscopy have
      changed the face of urolithiasis. Open surgery is becoming extremely rare today.
      Nevertheless, the cooperation between nephrologist and urologist remains
      essential and is the only way to prevent recurrence.

PMID- 15499205
TI  - Aetiological factors in paediatric urolithiasis.
AB  - The aetiology of stones in children differs from that in adults. Young children,
      especially boys, are prone to infective stones, although this type of calculi is
      decreasing in frequency over time in prosperous countries. Two monogenic causes,
      cystinuria and hyperoxaluria, each account for 5-15% of paediatric stones.
      Increased factors for stone formation in children include prematurity,
      neurological problems, ketogenic diet and reconstructed or augmented bladders.
      Hypercalciuria is commonly found in paediatric stone formers, is usually
      idiopathic and is only rarely associated with hypercalcaemia. All children with
      stones should undergo a metabolic evaluation.

PMID- 15499206
TI  - The molecular basis of cystinuria.
AB  - Cystinuria is an inherited form of nephrolithiasis due to failure of reabsorptive
      transport in the proximal tubule. Patients with classical recessive cystinuria
      have inherited two mutations of the SLC3A1 gene, encoding a subunit of the
      transport mechanism. Patients with the dominant form of cystinuria have inherited
      two mutations of the SLC7A9 gene, encoding the transport channel itself. A
      smaller subset of patients have mixed-type cystinuria, combining recessive and
      dominant mutant alleles. Children at risk for nephrolithiasis can be identified
      by the level of urinary cystine only after tubular transport has matured (age 2
      years). Conservative therapy with high urine volume and urinary alkalinization is
      sufficient for some, but recurrent stone formation may cause renal damage and
      warrants prophylaxis with agents that form mixed disulfides with cystine.

PMID- 15499207
TI  - Hypophosphatemia and calcium nephrolithiasis.
AB  - Our knowledge of phosphate balance under physiological and pathological
      situations has increased substantially during the last decade thanks to the
      molecular identification of three dissimilar families of sodium-phosphate
      cotransport systems, two of them almost exclusively expressed in epithelia
      whereas the third one has a ubiquitous expression. Intracellular proteins such as
      NHERF1 (sodium-proton exchanger regulatory factor 1) can interact with phosphate
      transporters through PDZ domains thus regulating the expression of the
      transporters at the membrane. Moreover, newly acknowledged paracrine/endocrine
      peptides, such as fibroblast growth factor 23 (FGF23), also affect the activity
      of phosphate transporters. Renal phosphate leak, related to invalidation (in the
      mouse) or to mutations (in humans) of the renal phosphate transporter NPT2a,
      leads to hypophosphatemia on the one hand, and to nephrolithiasis or bone
      demineralization on the other hand. Similar features are observed during
      invalidation of NHERF or in case of overproduction of FGF23. These observations
      highlight the importance of phosphate homeostasis in common diseases such as
      renal stones or bone loss.

PMID- 15499208
TI  - Role of renal epithelial cells in the initiation of calcium oxalate stones.
AB  - Normal urinary environment is inhibitory to crystallization. Occasional crystals
      are internalized by the renal epithelial cells and sequestered to lysosomes or
      externalized into the interstitium to be handled by the inflammatory cells.
      Elevated levels of oxalate and calcium oxalate crystals, however, provoke renal
      cells to increase the synthesis of osteopontin, bikunin, heparan sulfate
      proteoglycan, monocyte chemoattractant protein-1, and prostaglandin E(2), which
      are known mediators of the inflammatory processes and extracellular matrix
      production. Osteopontin and bikunin are also modulators of crystallization.
      Exposed renal epithelial cells are often injured and go through apoptosis and/or
      necrosis initiating a cascade of events leading to further crystallization,
      crystal retention and development of stone nidi. Reactive oxygen species are
      produced during the interactions between the oxalate/crystals and renal cells and
      are responsible for the various cellular responses. Calcium oxalate crystal
      deposition in the rat kidneys also activates the renin-angiotensin system. Both
      oxalate and calcium oxalate crystals selectively activate p38 mitogen-activated
      protein kinase in the exposed tubular cells. Extracellular environment changes
      from one that inhibits crystal nucleation, growth, aggregation and retention to
      that, which promotes these processes.

PMID- 15499209
TI  - Intracellular events in the initiation of calcium oxalate stones.
AB  - This review summarizes our current understanding of intracellular events in the
      initiation of kidney stone formation, focusing on results from studies using
      renal epithelial cells in vitro. Such studies have shown that oxalate - either in
      crystalline or in soluble form - triggers a spectrum of responses in renal cells
      that favor stone formation, including alterations in membrane surface properties
      that promote crystal attachment and alterations in cell viability that provide
      debris for crystal nucleation. Activation of cytosolic PLA2 appears to play an
      important role in oxalate actions, triggering a signaling cascade that generates
      several lipid mediators (arachidonic acid, AA; lysophosphatidylcholine, Lyso-PC;
      ceramide) that act on key intracellular targets (mitochondria, nucleus). The net
      effect is increased production of reactive oxygen molecules (that in turn affect
      other cellular processes), an increase in cell death and an induction of a number
      of genes in surviving cells, some of which may promote proliferation for
      replacement of damaged cells, or may promote secretion of urinary macromolecules
      that serve to modulate crystal formation. A scheme is provided that explains how
      such oxalate-induced alterations could initiate stone formation in vivo.

PMID- 15499210
TI  - Molecular aetiology of primary hyperoxaluria type 1.
AB  - Primary hyperoxaluria type 1 (PH1) is a rare autosomal-recessive disorder, caused
      by a deficiency of the liver-specific intermediary-metabolic enzyme
      alanine:glyoxylate aminotransferase (AGT). AGT deficiency results in increased
      synthesis and excretion of the metabolic end-product oxalate and the deposition
      of insoluble calcium oxalate in the kidney and urinary tract. Numerous mutations
      and polymorphisms have been identified in the gene (AGXT) that encodes AGT, some
      of which interact synergistically to cause a variety of complex enzyme
      phenotypes, including AGT intraperoxisomal aggregation, accelerated degradation,
      and peroxisome-to-mitochondrion mistargeting. The latter is the single most
      common cause of PH1 and results from the functional interaction between a common
      Pro11Leu polymorphism and a disease-specific Gly170Arg mutation. The recent
      solution of the crystal structure of AGT has enabled the effects of several
      mutations and polymorphisms to be rationalised in terms of their likely effects
      on AGT conformation. Increased understanding of the molecular aetiology of PH1
      has led to significant improvements in all aspects of the clinical management of
      the disorder, including diagnosis (by enzyme assay of percutaneous needle liver
      biopsies), prenatal diagnosis (by DNA analysis of chorionic villus samples) and
      treatment (by liver transplantation as a form of enzyme replacement therapy).

PMID- 15499211
TI  - Kidney models of calcium oxalate stone formation.
AB  - This review compares and contrasts three mathematical models used to describe the
      flow of urine through the renal tubule and the composition of tubular fluid
      throughout the length of the nephron. From these data the relative
      supersaturation of tubular fluid with respect to calcium oxalate (CaOx) is
      calculated at various points along the tubule. This shows that glomerular
      filtrate is well undersaturated with respect to CaOx and is still undersaturated
      at the end of the proximal tubule. By the end of the descending limb of the loop
      of Henle, it is highly supersaturated as a result of water reabsorption and CaOx
      may nucleate in this region, particularly when the tubular concentration of
      oxalate is increased. Supersaturation falls slightly by the end of the ascending
      limb and becomes briefly undersaturated again in the short distal tubule. The
      final water adjustment in the collecting tubules causes the supersaturation to
      rise to a very high value by the end of the collecting duct and spontaneous CaOx
      crystalluria is likely to occur. The review also examines the probability of
      these crystals growing large enough to be trapped at some point in the nephron
      within the transit time of tubular fluid from glomerular capsule to ducts of
      Bellini. All three models agree that, under normal conditions, the likelihood of
      individual crystals growing large enough to be trapped within the measured urine
      transit time of 3-4 min is very small. It is concluded that either there has to
      be aggregation of crystals or some other factor that delays the passage of
      crystals for them to grow large enough to become lodged at some point in the
      nephron. Three new hydrodynamic factors are introduced that may lead to delay of
      crystal passage: (a) fluid drag close to the tubule walls; (b) the drag effect of
      tubular walls on particles travelling close to the tubule walls, and (c) the
      effect of gravity on particles travelling in upward-draining sections of tubule.
      When these factors are introduced into the mathematical model of urine flow and
      tubular concentration, it is shown that any crystals that form at the end of the
      descending limb of the loop of Henle and which travel close to the tubular walls
      may be delayed long enough to grow large enough to become trapped further down
      the nephron, particularly in upward-draining sections of the nephron. This
      possibility becomes increasingly significant as urinary oxalate concentration
      increases. Crystals that nucleate in the late collecting duct, however, are
      readily passed as small crystals and are at no risk of being trapped in the
      tubular system. These predictions are used to explain data on the effects of
      oxalate loading on CaOx crystalluria in stone formers and normal controls. The
      data are interpreted as showing that if the additional hydrodynamic factors are
      added to the mathematical model of nephron function, then the 'free-particle'
      model of calcium stone formation is still possible. This possibility will be
      further enhanced if crystal aggregation also takes place during the period when
      crystal passage is delayed by these factors.

PMID- 15499212
TI  - Clinical value of crystalluria and quantitative morphoconstitutional analysis of
      urinary calculi.
AB  - Morphoconstitutional analysis of urinary calculi, i.e. morphologic examination
      combined with Fourier transform infrared spectroscopy (FTIR), is of decisive
      interest for the diagnosis of rare but severe inherited or acquired stone
      diseases such as cystine, 2,8-dihydroxyadenine, xanthine, struvite, ammonium
      urate or drug-containing calculi as well as primary hyperoxalurias. In the
      absence of early diagnosis and proper management, these diseases may lead to
      progressive loss of renal function. Among common forms of calcium oxalate (CaOx)
      stones, predominant CaOx monohydrate (whewellite) is mainly associated with
      hyperoxaluric conditions whereas predominant CaOx dihydrate (weddellite) is
      mainly associated with hypercalciuria, and this distinction is of interest to
      orient metabolic evaluation and preventive measures. Crystalluria examination,
      also based on morphology and FTIR, is a valuable diagnostic method when no stone
      is available for analysis. Presence of specific crystals (cystine, 2,8
      dihydroxyadenine, struvite, ammonium urate) is diagnostic by itself. In all types
      of nephrolithiasis, serial crystalluria determination appears as a simple, cheap
      and reliable method to evaluate the risk of stone formation and assess the
      effectiveness of preventive measures. Determination of urinary crystal volume was
      in our experience a useful tool in the management of patients with cystinuria or
      primary hyperoxaluria in the post-transplantation period. In conclusion, both
      accurate morphologic and FTIR analysis of stones and serial crystalluria
      determination should be more largely used, in view of their value in the
      diagnosis and management of renal stone formers.

PMID- 15499213
TI  - Macromolecules and urolithiasis: parallels and paradoxes.
AB  - Long-standing interest in the possible role of macromolecules in urolithiasis
      stems from the observation that all human kidney stones consist of a complex
      amalgam of mineral and organic material. This review summarises what is currently
      known or is hypothesised about the influences of urinary macromolecules,
      especially proteins, on the formation of calcium oxalate crystals, their
      attachment to renal epithelial cells, and their subsequent destruction within
      those cells. Although a list is provided of proteins that have either been
      detected in stones or have been implicated by virtue of their effects on
      crystallization, only a select handful, which have been intensively studied, have
      been singled out for individual discussion. The review ends with a speculative
      discussion of the applicability of current knowledge to the investigation and
      treatment of urolithiasis.

PMID- 15499214
TI  - Osteopontin and calcium stone formation.
AB  - Osteopontin (OPN) is a phosphorylated protein of wide tissue distribution that is
      found in association with dystrophic calcification including in the organic
      matrix of kidney stones. It is a strong inhibitor of crystal formation and growth
      in vitro, but there is still debate regarding its effects upon crystal adhesion
      to tubular epithelial cells. In this brief review, we will outline the evidence
      implicating OPN in stone disease with the primary emphasis being on the
      interaction of OPN with calcium oxalate (CaOx), the major constituent of calcium
      containing stones. Finally, preliminary data is presented regarding the amounts
      and features of OPN present in the urine of stone formers and normal individuals.

PMID- 15499215
TI  - Microorganisms and calcium oxalate stone disease.
AB  - Microorganisms may have a role in the pathogenesis and prevention of kidney
      stones. The subjects of this review include nanobacteria, Oxalobacter formigenes,
      and lactic acid bacteria. Not reviewed here is the well-described role of
      infections of the urinary tract with Proteus species and other urease-producing
      organisms associated with struvite stone formation. Nanobacteria have been
      proposed to be very small (0.08-0.5 nm), ubiquitous organisms that could play a
      role in stone formation. The theory is that nanobacteria can nucleate carbonate
      apatite on their surfaces and thereby provide the nidus for stone formation.
      However, their existence remains uncertain and many investigators are openly
      skeptical. Recent investigations suggest that they are artifacts, and not
      actually living organisms, but their proponents continue to study them. O.
      formigenes is an obligate anaerobe which may be important in the prevention of
      stone formation. Its sole substrate for generation of ATP is oxalate. It may
      thereby metabolize its human host's dietary oxalate and diminish intestinal
      absorption and subsequent urinary excretion of oxalate. There is evidence that
      the organism's absence, perhaps sometimes due to courses of antibiotics, may be a
      cause of hyperoxaluria and stone formation. In early investigations, patients not
      colonized with the organism can be recolonized. Urinary oxalate can be diminished
      by accompanying an oxalate-containing meal with the organism. One study
      demonstrated that a preparation of lactic acid bacteria successfully reduced
      urinary oxalate excretion in 6 patients with calcium oxalate stones and
      hyperoxaluria. The mechanism of this effect is uncertain since these bacteria
      lacked the gene possessed by O. formigenes which codes for that organism's
      oxalate uptake mechanism. The author is currently completing a small randomized
      controlled clinical trial with this preparation in calcium stone-forming patients
      with idiopathic hyperoxaluria.

PMID- 15499216
TI  - Role of nutrition in the formation of calcium-containing kidney stones.
AB  - Diet plays an important role in the pathogenesis of calcium-containing kidney
      stones. Although much work has demonstrated that specific dietary components
      alter urinary composition and supersaturation, relatively few studies link the
      ingestion of these components with actual nephrolithiasis. This article reviews
      the dietary factors thought to promote or inhibit the formation of calcium stones
      and discusses the current controversies in the field of nutrition and
      nephrolithiasis. Special attention is paid to the roles of dietary calcium,
      supplemental calcium, oxalate, phytate, and n-3 fatty acids. We offer dietary
      recommendations to individuals who have suffered from a calcium-containing kidney
      stone, and emphasize that a patient's 24-hour urine chemistries should be used to
      help guide dietary intervention.

PMID- 15499217
TI  - Role of dietary intake and intestinal absorption of oxalate in calcium stone
      formation.
AB  - The factors affecting the urinary excretion of oxalate are critical to the risk
      of forming calcium oxalate stones. This article reviews the role of dietary and
      intestinal oxalate in determining the level of oxalate excreted in urine. The
      amount of oxalate available for absorption throughout the intestine is highly
      dependent on the state of oxalate (a) in the food ingested, and (b) in the
      intestinal contents at each section of the intestinal tract since only the
      soluble form of oxalate can be absorbed. In this respect, the solubility of
      calcium oxalate (CaOx) under the prevailing conditions is paramount in
      determining the amount of oxalate available for absorption at any particular
      site. In turn, the main factors that control how much oxalate is in the soluble
      form are pH and the concentrations of calcium, magnesium and (indirectly)
      phosphate. Based on these parameters, a model of the intestine has been
      constructed which brings together the available evidence on the prevailing
      concentrations of these various factors at different sites in the intestine after
      allowing for dietary intake and the concentration of the above ions in intestinal
      secretions. The model then calculates the likely concentration of oxalate that is
      in the soluble form at each site and therefore available for passive absorption
      at that site. The model shows that oxalate is likely to be absorbed in the
      stomach, although it can be also absorbed in the small intestine, particularly at
      the distal end (after the absorption of calcium), and in the colon, since, on a
      normal intake of calcium and phosphate, most of the calcium in the large bowel
      would be anticipated to be precipitated as calcium phosphate under the prevailing
      alkaline conditions and high concentration of phosphate. The amount of free
      oxalate in the colon is also controlled by the presence or absence of Oxalobacter
      formigenes, an anaerobe that has an obligate requirement for oxalate as a source
      of energy and cellular carbon.

PMID- 15499218
TI  - An overview of divalent cation and citrate handling by the kidney.
AB  - Urinary calcium, magnesium and citrate levels are important in promoting or
      inhibiting renal stone formation. Here we review current information on the
      tubular handling of these ions. Most filtered calcium is reabsorbed in the
      proximal tubule and the thick ascending limb (TAL) of the loop of Henle, largely
      paracellularly; most of the remainder is reabsorbed in the distal tubule,
      transcellularly. Calcium reabsorption in the TAL and distal tubule is stimulated
      by parathyroid hormone and vitamin D; other factors influencing its renal
      handling include extracellular volume status and acid-base balance. Little
      filtered magnesium is reabsorbed in the proximal tubule; the bulk is reabsorbed
      paracellularly in the TAL, while most of the remainder is reabsorbed
      transcellularly in the distal tubule. Dietary intake, peptide hormones and
      chronic potassium depletion can all influence magnesium reabsorption in the TAL
      and distal tubule. Most filtered citrate is taken up across the apical membrane
      of the proximal tubule via a sodium-dicarboxylate co-transporter (NaDC-1). It
      also enters proximal tubular cells across the basolateral membrane; citrate
      contributes to the cells' oxidative metabolism. Citrate excretion is affected by
      acid-base balance, acetazolamide treatment, chronic potassium depletion and
      urinary excretion of calcium and magnesium. Where possible, we have indicated the
      mechanisms of these complex interactions.

PMID- 15499219
TI  - Effects of mycophenolate mofetil and lisinopril on collagen deposition in
      unilateral ureteral obstruction in rats.
AB  - BACKGROUND/AIMS: Unilateral ureteral obstruction (UUO) in rats has been used as a
      model of renal interstitial fibrosis, in which therapeutic trials can be of
      important clinical relevance. In this study, we investigated the effects of
      mycophenolate mofetil (MMF), the angiotensin-converting enzyme (ACE) inhibitor
      lisinopril (L), and the combination of both drugs, given daily for 14 days to UUO
      rats, on the renal fibrogenic process triggered by UUO. METHODS: Rats underwent
      surgical UUO, followed by treatment with daily doses of either MMF, lisinopril,
      or both, and were then sacrificed after 14 days. Kidney fragments were fixed for
      histopathological examination (hematoxylin-eosin and periodic acid-Schiff
      reactive) and immunohistochemistry for myofibroblasts (alpha-smooth muscle actin;
      alpha-SMA) and macrophages (ED-1). Histomorphometrical analysis of collagen was
      performed with Sirius red staining, and collagen content was assessed by the
      amount of hydroxyproline. Cortex and medulla were analyzed separately. RESULTS:
      MMF, lisinopril and MMF+L reduced the density of alpha-SMA- and ED-1-positive
      cells (p < 0.05), interstitial volume (p < 0.05) and decreased Sirius-red-stained
      areas by 54.6, 35.6 and 58.0%, and hydroxyproline content by 60.1, 49.7 and
      62.7%, respectively. No differences were observed among treated groups.
      CONCLUSION: MMF and the ACE inhibitor lisinopril attenuated the progression of
      the fibrogenic process of UUO in an equivalent manner. The combination of both
      drugs did not add any further improvement in the collagen content.

PMID- 15499220
TI  - Effects of Trifolium alexandrinum extracts on streptozotocin-induced diabetes in
      male rats.
AB  - The effects of (water, hexane and ethanolic) extracts prepared from the flower
      head of Trifolium alexandrinum (Leguminosae) were examined in the treatment of
      diabetes induced experimentally by streptozotocin (STZ) in rats. A single dose of
      STZ (50 mg/kg) produced a hyperglycemia, decrease in insulin level and elevation
      in glycosylated hemoglobin of RBCs as well as elevated serum total lipids,
      triglycerides and cholesterol levels. Also, a decreased serum high-density
      lipoprotein and in hepatic glycogen and glutathione GSH contents, concurrent with
      an increase in the concentration of malondialdehyde in the liver was observed.
      Daily intake of (water, hexane and ethanolic) extracts of T. alexandrinum in
      drinking water for 4 weeks immediately after diabetes induction caused
      significant decreases in glucose and glycated hemoglobin levels and increase in
      insulin level. It also greatly improved the levels of serum lipid parameters and
      significantly decreased lipid peroxidation in addition to increase the hepatic
      GSH content significantly. CONCLUSION: Extracts of T. alexandrinum improved
      hyperglycemia and other biochemical alterations noticed in STZ-diabetic rats.
      These effects may be due to the presence of a high content of flavonoids which
      acts synergistically as antioxidants.

PMID- 15499222
TI  - Ileo-neorectal anastomosis: medium- and long-term follow-up of 37 patients.
AB  - BACKGROUND: Ileo-neorectal anastomosis (INRA), an alternative restorative
      procedure, was developed to reduce the pouch-related complication rate with an
      (at least) equal functional result. METHODS: For this surgical outcome, data of
      all INRA patients, including bowel function and complications, were prospectively
      recorded. The reservoir capacity was determined repeatedly by physiologic tests.
      The anal sphincter complex was assessed by manometry and ultrasound examination.
      Evaluation of the neorectal mucosa was performed by endoscopy. RESULTS: An INRA
      procedure was carried out in 39/53 selected patients (47 ulcerative colitis and 6
      familial adenomatous polyposis). Fourteen UC cases were converted to ileal pouch
      anal anastomosis or proctectomy only, because of impossibility to completely
      remove the rectal mucosa or short of length of the rectal stump. The median
      operation time for INRA was 323 min (range 240-518), with 1,400 ml blood loss
      (400-4,500). The reservoirs were permanently defunctioned in 2 patients--one
      because of reclassification into Crohn's disease, and one with pouchitis
      refractory to medical treatment. In 18 out of 37 cases, web-like stenoses
      occurred at the mucosa-anal level, which were treated by single (9) or repeated
      (5) dilatation or surgical stenoplasty (2). No pouch-related complications like
      pelvic sepsis, fistula or sexual dysfunction occurred. Thirteen patients had
      episodes of 'pouchitis', successfully treated with antibiotics, and 7 other
      cases, with functioning reservoirs, also had proximal 'non-specific' (i.e. no
      histological criteria of Crohn's disease found) small bowel inflammation. The
      median bowel frequency decreased from 15x/24 h initially to 7x/24 h at 2 years.
      Continence was perfect in 24/37 cases. Twelve out of 37 cases had occasional
      nocturnal soiling and passive nocturnal fecal incontinence was reported by 2/37
      patients. The neorectal compliance volume recovered from 12.5 ml kPa after
      subtotal colectomy and 11 ml/kPa at 6 months after INRA to a neorectal compliance
      of 24 ml/kPa at 2 years' follow-up (p < 0.002; Wilcoxon signed rank test).
      CONCLUSION: The INRA procedure shows a low complication rate and reasonable
      functional results, there was however a considerable conversion rate in these
      first 53 cases and a high incidence of reclassification to CD.

PMID- 15499223
TI  - Multivariate analysis on factors affecting suppression of thyroid-stimulating
      hormone in treated congenital hypothyroidism.
AB  - AIMS: To determine the factors which influence the suppression of thyroid
      stimulating hormone (TSH) in infants with congenital hypothyroidism (CH)
      following treatment. METHODS: We examined retrospectively the patterns of thyroid
      function tests from diagnosis to 3 years of age in 140 infants diagnosed with CH
      from screening. Patients were classified into 3 groups: athyreosis, ectopia and
      presumed dyshormonogenesis on the basis of thyroid scans. Adequate TSH
      suppression was defined as plasma TSH concentration <6 mU/l. The factors
      affecting the suppression of TSH at 6 months and 1 year of age which were
      evaluated were: initial confirmatory plasma TSH, initial plasma thyroxine (T4),
      mean age of starting treatment with L-T4, dose of L-T4 at diagnosis, 6 weeks, 3
      months and 6 months, and aetiology of the congenital hypothyroidism. Variables
      were then entered in a stepwise logistic regression model for TSH suppression at
      6 months and 1 year of age. RESULTS: All infants had radionuclide scans prior to
      treatment: athyreosis (n = 39), ectopia (n = 78) and dyshormonogenesis (n = 23).
      58% of patients had persistently raised TSH at 6 months of age while 31% of
      patients had a persistently raised TSH at 1 year of age. There was a significant
      delay in the normalisation of plasma TSH in athyreosis and ectopia groups
      compared with dyshormonogenesis. Multiple regression analysis for TSH suppression
      at 6 months of age found plasma T4 levels and aetiology of CH as independent
      factors affecting the timing of TSH suppression. Aetiology of CH was the only
      independent factor affecting TSH suppression at 1 year of age. CONCLUSION: At 6
      months of age, plasma T4 levels at 6 weeks and 3 months, and aetiology of CH were
      independent factors affecting timing of TSH suppression. However, by 1 year of
      age, the aetiology of CH was the only independent factor affecting suppression of
      TSH.

PMID- 15499224
TI  - Pharmacodynamic equivalence of a decapeptyl 3-month SR formulation with the 28
      day SR formulation in patients with advanced prostate cancer.
AB  - AIMS: The objective of the study was to assess the pharmacodynamic equivalence of
      LHRH analogue triptorelin 3-month and 28-day SR formulations. METHODS: Patients
      with documented locally advanced or metastatic prostate cancer were randomized to
      receive one injection of the 3-month formulation (n = 63) or three injections at
      28-day intervals of the 28-day formulation (n = 68). Group-chemical castration
      rates defined as the percentage of patients reaching a testosterone plasma level
      </=0.5 ng/ml were compared at D84 (i.e., 3 x 28 days). Testosterone, LH and
      triptorelin plasma profiles, and change from baseline in plasma PSA were assessed
      over 3 months (from baseline to D91). RESULTS: Chemical castration rates were 98
      and 96% in the 3-month and 28-day formulation groups, respectively, with
      confidence interval (two-sided 94.2% CI) of [-8.1%; 9.6%]. Median times to reach
      chemical castration were 18.8 and 18.5 days (p = 0.86, log rank), respectively.
      Ratios for mean peak plasma levels and AUC(91) of the two formulations for both
      testosterone and LH fell within the [0.80; 1.25] equivalence interval. Mean PSA
      decreases from baseline at D91 were 91.0 and 91.7%, respectively (p = 0.73).
      CONCLUSION: Treatments with the two triptorelin formulations over 3 months are
      pharmacologically equivalent.

PMID- 15499225
TI  - Atorvastatin and simvastatin decrease the uptake of acetylated low-density
      lipoprotein by human monocytes.
AB  - Several lines of evidence indicate that HMG-CoA reductase inhibitors, calcium
      channel blockers, and angiotensin-converting enzyme inhibitors exert anti
      atherogenic effects in vitro and in vivo. In the present study, we determined the
      effect of members of the above classes of drugs on the uptake of modified low
      density lipoprotein (LDL) by U937 cells (human monocytic cell line), a key event
      in the progression of atherosclerosis. U937 cells were treated with drugs and
      subsequently the uptake of fluorescent acetylated LDL was assessed by flow
      cytometry. The HMG-CoA reductase inhibitors, atorvastatin and simvastatin (1-30
      mumol/l), but not calcium channel blockers or angiotensin-converting enzyme
      inhibitors, inhibited the uptake of modified LDL by monocytes. Therefore,
      atorvastatin and simvastatin may slow down the progression of atherosclerosis by
      inhibiting the formation of foam cells.

PMID- 15499226
TI  - Effect of potassium channel and cytochrome P450 inhibition on transient
      hypotension and survival during lipopolysaccharide-induced endotoxic shock in the
      rat.
AB  - The purpose of this study was to determine whether inhibition of potassium
      channels or cytochrome P450 attenuates the transient phase of hypotension during
      endotoxic shock in vivo, and to determine whether these interventions improve the
      rate of survival. Male Sprague-Dawley rats were pretreated with saline (0.2 ml,
      i.v.), tetraethylammonium chloride (TEA 30 mg/kg; 0.2 ml, i.v.), proadifen (SKF
      525 A; 50 mg/kg, i.p.) or ketoconazole (50 mg/kg, i.p.) and challenged with
      lipopolysaccharide (LPS; 20 mg/kg, i.p.). Changes in heart rate, mean (MAP),
      systolic (SP) and diastolic (DP) arterial pressures as well as survival rate were
      then monitored for 45 min. Potassium channel inhibition with TEA had no effect on
      LPS-induced hypotension at any time point compared with saline (maximal fall in
      MAP of 79 +/- 18 and 80 +/- 13 mm Hg, respectively). Pretreatment with proadifen
      or ketoconazole, inhibitors of cytochrome P450, significantly attenuated LPS
      induced hypotension compared with saline (maximal fall in MAP of 34, 26 and 63%
      below baseline, respectively). This effect was evident in all arterial pressures
      measured, MAP, SP and DP. At 45 min, the survival rate in the saline group was
      66%. Pretreatment with TEA significantly reduced survival rate to 50% and
      pretreatment with proadifen or ketoconazole improved survival to 100% (p < 0.05).
      These results suggest that an arachidonic acid metabolite produced by a
      cytochrome P450-catalyzed reaction may contribute to the transient phase of LPS
      induced hypotension. However, these effects do not appear to be mediated through
      potassium channel activation.

PMID- 15499227
TI  - MRI changes in the rat hippocampus following proton radiosurgery.
AB  - PURPOSE: To define radiographic dose-response relationships for proton
      radiosurgery using a rat brain model. METHODS AND MATERIALS: A group of 23 rats
      was treated with Bragg peak proton beam irradiation involving the right
      hippocampus. Single doses of 5, 12, 20, 30, 60, 90 and 130 cobalt gray
      equivalents (CGE) were delivered to groups of 3 animals using single fraction
      technique. One extra animal was included at the 130- and 30-CGE doses. Animals
      were imaged using a standard 1.5-tesla GE Signa MRI. A 3-inch surface coil was
      employed to obtain T1-weighted sagittal images (TR 600 and TE 30) and dual echo
      T2-weighted coronal images (TR 3,000 and TE 30/90). Animals were imaged at 1.5,
      3, 4.5, 6 and 9 months. Volumetric analysis with custom software was done to
      evaluate areas of increased signal on T2-weighted images, and signal change
      versus time curves were generated. Gadolinium-enhanced T1-weighted imaging was
      also done at the 9-month time point to further evaluate tissue injury. The
      development of hydrocephalus was also examined. RESULTS: Peak tissue injury was
      greater and occurred earlier with higher versus lower doses of radiation.
      Statistically significant differences were seen between the 130- and 90-CGE
      animals and between the 90- and 60-CGE animals (p < 0.0016) using ANOVA. Signal
      changes can be seen in at least 1 of the animals at 20 CGE. The largest volume of
      tissue enhancement at 9 months was seen in animals at 60 CGE, which may represent
      an intermediate zone of tissue injury and gliosis compared with greater tissue
      loss at higher doses and less injury at lower doses. Hydrocephalus developed
      first in the untreated hemisphere in 130- and 90-CGE animals as a result of mass
      effect while it occurred at a later time in the treated hemisphere in lower-dose
      animals. CONCLUSIONS: Following single-dose proton radiosurgery of rat
      hippocampus, serial MRIs show T2 signal changes in animals ranging from 130 down
      to 20 CGE as well as the development of hydrocephalus. Dose-effect relationships
      using proton radiosurgery in rats will be a helpful step in guiding further
      studies on radiation injury to brain tissue.

PMID- 15499228
TI  - Orthokeratology: old devil or new saint?

PMID- 15499229
TI  - Subepithelial intracorneal hemorrhage in a soft contact lens user.
AB  - PURPOSE: To describe a case of spontaneous subepithelial hemorrhage in a soft
      contact lens user. METHODS: A 45-year-old man with irritation and decreased
      vision had four-quadrant pannus and corneal subepithelial hemorrhage in an
      annular pattern. RESULTS: The subepithelial hemorrhage was drained and the feeder
      vessel coagulated. The hemorrhage subsequently absorbed with time. CONCLUSIONS:
      Soft contact lens users should be monitored for the development of significant
      neovascularization.

PMID- 15499230
TI  - Contact lens assisted pharmacologically induced keratoshaping.
AB  - PURPOSE: To retrospectively evaluate the effectiveness and describe the process
      of reducing hyperopia with a nonsteroidal antiinflammatory agent and a soft
      disposable contact lens in postoperative excimer laser patients with consecutive
      hyperopia. SETTING: Private practice. METHODS: This study includes a
      retrospective analysis of 14 eyes of 12 patients who underwent laser in situ
      keratomileusis or photorefractive keratectomy and experienced consecutive
      hyperopia. Patients were treated with a tightly fit, extended-wear contact lens
      in combination with the use of ketorolac tromethamine 0.5% (Acular) in an attempt
      to steepen the cornea. Uncorrected visual acuity, manifest refraction, and
      slitlamp examination were performed on a weekly basis until the desired outcome
      was achieved or until treatment was discontinued. RESULTS: A total of 78.57% of
      eyes experienced a decrease in consecutive hyperopia (>or=0.50 diopters [D]) (P =
      0.002). The mean dioptric change was 1.05D. A total of 88.89% of eyes experienced
      an increase in uncorrected visual acuity (>or=1 line) (P < 0.001). The mean
      increase was three lines of Snellen or Jaeger acuity. The mean number of weeks to
      see an effect was 1.71 weeks, and the mean number of weeks to achieve endpoint
      was 8.29 weeks (median, 6 weeks). CONCLUSIONS.: Contact lens-assisted
      pharmacologically induced keratoshaping is an effective treatment option for
      patients who experience consecutive hyperopia after laser in situ keratomileusis
      or photorefractive keratectomy.

PMID- 15499231
TI  - Determination of microdot stromal degenerations within corneas of long-term
      contact lens wearers by confocal microscopy.
AB  - PURPOSE: To ascertain whether a relationship exists between the presence of
      microdot deposits within the corneal stroma of long-term contact lens wearers as
      seen by confocal microscopy and the contact lens wear time, material, or other
      patient variables. METHODS: Thirty-six myopic patients with a 15- to 43-year
      history of hard, rigid gas-permeable, or soft hydrogel contact lens wear and 12
      age-matched emmetropic or spectacle-corrected myopic volunteers were included in
      this study. The numerical density and size of microdot deposits within the
      anterior, mid, and posterior stroma were determined with the confocal microscope,
      and the data were subjected to multiple regression statistical analysis. RESULTS:
      Microdot deposits were encountered throughout the entire depth of the corneal
      stroma in all contact lens wearers. None of the control subjects showed microdot
      deposits. The numerical densities and the size range of microdots were similar in
      each of the stromal layers (anterior, mid, and posterior), with total mean values
      (+/- SD) for each parameter being 65.1 x 10(3) +/- 26.9 x 10(3) dots/mm (range,
      21.4 x 10(3) to 121.1 x 10(3) dots/mm) and 3.04 +/- 0.92 microm (range, 1.5-5.0
      microm), respectively. CONCLUSIONS: Microdot deposits may represent granules of
      lipofuscinlike material within the corneal stroma of long-term contact lens
      wearers, formed as a result of chronic oxygen deprivation and chronic microtrauma
      to the cornea. No one in the control group showed microdot deposits. Among the
      independent variables, soft contact lens wear time had the most profound
      influence on numerical microdot density and size in our statistical equations.

PMID- 15499232
TI  - A comparison of tear volume (by tear meniscus height and phenol red thread test)
      and tear fluid osmolality measures in non-lens wearers and in contact lens
      wearers.
AB  - PURPOSE: Various measures are available to assess the tear film, yet little
      specific information is available on how they relate to each other. An
      exploratory study was undertaken to assess three measures and their relationship
      in non-contact lens wearers and in contact lens wearers. METHODS: Forty-three
      young subjects (mean age, 25.0 +/- 3.1 years; 19 men and 24 women) without overt
      ocular disease were recruited and categorized into four similarly sized groups
      based on contact lens wear (no lens wear, conventional daily wear hydrogels,
      silicone hydrogel lenses worn on a continuous basis, and gas-permeable contact
      lenses). Sets of measures, in random order and from both eyes whenever possible,
      were made using a phenol red thread (PRT) test over 15 seconds (open eye),
      biomicroscopy to assess tear meniscus height (TMH) from a perpendicular
      perspective using a 0.05-mm resolution graticule, and a borosilicate glass
      micropipette used to collect a 5-microL sample of tears for assessment of
      osmolality by vapor pressure measures. RESULTS: For the complete group of
      subjects, the TMH data averaged 0.22 +/- 0.07 mm; the average PRT wetting length
      was 18.0 +/- 6.1 mm; and the tear osmolality averaged 317 +/- 28 mOsm/kg. The
      intereye differences averaged 0.04 mm for TMH, 3.7 mm for PRT, and 15 mOsm/kg for
      tear osmolality. There were no detectable sex-related differences in the
      measures. Compared with the control group (average, 0.25 mm), the TMH data showed
      a trend to be lower in daily hydrogel (0.21 mm) and silicone hydrogel (0.20 mm)
      lens wearers, but not in gas-permeable lens wearers (0.24 mm). PRT data was
      bimodally distributed, with the control group showing slightly higher (average,
      21.1 mm) wetting compared with hydrogel lens wearers (16.7 and 17.4 mm) and gas
      permeable lens wearers (average, 17.3 mm). Hydrogel (319 mOsm/kg for both groups)
      and gas-permeable lens wearers (average, 324 mOsm/kg) had higher tear osmolality
      measures compared with the control group (average, 305 mOsm/kg). Although some of
      the differences approached statistical significance, any statistical differences
      were evident only after outliers were removed. However, on pooling all data,
      there was a statistically significant positive correlation between TMH and open
      eye PRT measures (P < 0.001) and an indication of a negative correlation between
      open-eye PRT and tear osmolality measures. CONCLUSIONS: Even contemporary contact
      lens wear can have a small but measurable impact on the precorneal tear film
      osmolality or volume. The changes are internally consistent and, overall, support
      the idea that the PRT test provides a useful measure of tear meniscus volume.

PMID- 15499233
TI  - Forms of vision correction: demographic factors in patient attitudes and
      perceptions.
AB  - PURPOSE: To evaluate attitudes toward current treatments for vision correction in
      a clinical population of adults wearing spectacles and contact lenses (CLs).
      METHODS: Patients seen in the Indiana University Contact Lens and Primary Care
      Clinics in the spring of 2002 completed multiple-choice questionnaires evaluating
      their current device for vision, comfort, convenience, health and safety, cost,
      and overall satisfaction. They also rated their interest in and the convenience
      and health and safety of 30-day continuous wear (CW), 7-day extended wear (EW),
      modern orthokeratology, and LASIK and were given a forced choice on their
      preferred method of vision correction. RESULTS: Three hundred forty-nine CL and
      177 primary care patients completed questionnaires. Subjects reported high
      satisfaction with their current treatment. Seventy percent of glasses wearers
      were neutral or not interested in CLs or LASIK. CL patients were interested or
      very interested in orthokeratology (70%) followed by LASIK (65%), 7-day EW (51%),
      and 30-day CW (44%). Age and sex were the most significant factors that
      influenced wearing practices and attitudes, with males (especially young)
      indicating significantly higher use of EW than females (P = 0.0005, chi(2)).
      Males were also more interested in 7-day EW (P = 0.011) and 30-day CW (P = 0.001)
      and rated their health and safety higher (P = 0.045 and P = 0.003, respectively).
      CONCLUSIONS: In the spring of 2002, many of these patients remained cautious
      about the health and safety of 7-day EW and 30-day CW CLs.

PMID- 15499234
TI  - Contact lens management of keratectasia after laser in situ keratomileusis for
      myopia.
AB  - PURPOSE: To present a case in which rigid gas-permeable contact lenses were fit
      for a patient in whom keratectasia developed after laser in situ keratomileusis
      (LASIK). METHODS: Case report. RESULTS: A 21-year-old man underwent bilateral
      LASIK for myopia and astigmatism. The left eye was only partially corrected
      because of high myopia and corneal thickness restrictions. Eight months after
      LASIK, visual acuity was reduced in the right eye; the central cornea had
      steepened; and pachymetry showed central corneal thinning. Keratectasia was
      diagnosed, and rigid contact lenses were fitted. Four years later, the patient
      achieved satisfactory visual acuity and all-day lens wear with minimal
      complications. CONCLUSIONS: The options for management of iatrogenic keratectasia
      include contact lenses, intracorneal ring segments, and penetrating keratoplasty.
      This case report shows that rigid contact lenses offer a safe, reversible option
      for improving visual acuity in such patients by delaying or avoiding the need for
      further surgical intervention.

PMID- 15499235
TI  - Keratoconus fittings: apical clearance or apical support?
AB  - PURPOSE: To examine the relative merits of apical support and apical clearance
      fitting of rigid gas-permeable contact lenses for keratoconus. METHODS: After an
      historic review of fitting approaches for keratoconus, a case report is described
      in which an adventitious apical clearance fitting for early keratoconus might
      have been associated with accelerated progress of the ectasia. DISCUSSION: The
      hypothesis that apical clearance fittings increase the risk of accelerating
      ectasia progression in early keratoconus is examined in counterpoint to the
      hypothesis that apical support fittings increase the risk of apical scarring.
      Reference is made to the responses of normal corneas to apical clearance fitting
      and to apical contact fittings used in orthokeratology fittings. The tendency for
      corneas to mold to contact lens curvature is reviewed. The possibility that
      reduced corneal thickness or tissue softening and associated changes to the
      biomechanical properties of the cornea in keratoconus may facilitate molding with
      apical clearance fitting is examined. CONCLUSIONS: Known and putative risk
      factors for fitting complications that are associated with apical clearance and
      apical touch contact lens fitting are given as a basis for the reader to draw
      conclusions about the management of contact lens fitting for keratoconus. The
      possibility of symptomless adverse responses is a strong indication for frequent
      routine aftercare reviews.

PMID- 15499236
TI  - Hyperopic photorefractive keratectomy with adjunctive topical mitomycin C for
      refractive error after penetrating keratoplasty for keratoconus.
AB  - OBJECTIVE: To present a case of photorefractive keratectomy (PRK) with adjunctive
      topical mitomycin C (MMC) in an anisometropic hyperopic patient after penetrating
      keratoplasty (PKP) for keratoconus. METHODS: Interventional case report, chart
      review, and literature review. RESULTS: A 43-year-old man with a refraction of
      +7.00 -4.75 x 125 in the right eye underwent PRK 10 months after PKP for
      keratoconus. The patient had sutures removed for 3 months and was intolerant of
      contact lenses. After photoablation, 0.02% MMC was applied to the corneal stromal
      bed. The patient was followed up daily until the epithelium closed and at 1 week,
      1 month, 3 months, and 6 months postoperatively. CONCLUSIONS: To our knowledge,
      this represents the first reported case of the use of MMC to prevent
      postoperative haze after PRK for PKP in an eye with keratoconus. MMC (0.02%)
      applied topically to the cornea immediately after PRK is safe and effective to
      treat a hyperopic refractive error after PKP and prevent postoperative corneal
      haze formation without the risks of performing a lamellar flap into an ectatic
      corneal bed.

PMID- 15499237
TI  - Vitamin A deficiency in Afghanistan.
AB  - PURPOSE: To evaluate children 6 years old and younger, lactating mothers, and
      women of childbearing age for vitamin A deficiency in the districts of Kabul
      City, Afghanistan. METHODS: A set number of patients selected randomly in all 13
      districts of the city limits were examined between August and September 2000 for
      ocular signs of vitamin A deficiency. RESULTS: Night blindness, Bitot's spot,
      corneal ulceration, and corneal scars were seen in increased amounts as defined
      by the World Health Organization among the sampled population. CONCLUSIONS:
      Vitamin A deficiency is a moderate to severe public health problem in children
      and lactating mothers in Kabul City, Afghanistan.

PMID- 15499238
TI  - Effectiveness of contact lens disinfectants after lens storage.
AB  - PURPOSE: To determine the effectiveness of multipurpose contact lens solutions
      after incubation with lenses for one week. METHODS: Five multipurpose solutions,
      three lots each, were preincubated with contact lenses for one week. The
      solutions were removed and one of three microbes was added to a final
      concentration of l x l0(6)/mL. The inoculated solutions were incubated for 4 and
      6 hours; aliquots were then neutralized, serially diluted, and plated. Plate
      counts were used to determine the approximate number of organisms that were
      killed effectively by the contact lens solution. RESULTS: Of the five solutions
      tested, only OPTI-FREE Express maintained full effectiveness after preincubation
      with lenses. The other solutions were effective only with Fusarium solani after
      the preincubation period. CONCLUSIONS: We propose that the active component was
      sufficiently reduced by absorption or inactivation during storage with contact
      lenses such that it was rendered effective only for F. solani and was no longer
      concentrated enough to be effective with the bacterial species.

PMID- 15499239
TI  - Corneal topography in corneal refractive therapy (CRT): a 1-month follow-up.
AB  - PURPOSE: To evaluate visual outcome and corneal shape change during the first
      month of wearing corneal refractive therapy (CRT) reshaping contact lenses to
      correct myopia in otherwise healthy eyes. METHODS: Twenty-nine eyes were fit with
      Paragon CRT contact lenses, which were worn nightly. Before and after CRT
      fitting, uncorrected visual acuity was measured, and corneal topography was
      performed and evaluated with the Holladay Diagnostic Summary EyeSys 2000
      Videokeratoscope. To evaluate the visual outcome, refractive yield
      (achieved/attempted correction) was calculated and accounted for distance or
      monovision. RESULTS: Uncorrected visual acuity improved in all patients. In 1
      month, refractive yield was 96.7%. Corneal uniformity index and predicted corneal
      acuity index were maintained, and the Q value changed from -0.08 to +0.38 (P <
      0.05). CONCLUSIONS: CRT lenses are effective in improving visual acuity. They
      significantly changed the corneal from prolate to oblate while maintaining
      corneal quality.

PMID- 15499240
TI  - Corneal intrastromal gatifloxacin crystal deposits after penetrating
      keratoplasty.
AB  - BACKGROUND: An 85-year-old man developed faint crystallike white precipitates in
      the mid peripheral stroma of his left cornea 3 weeks after undergoing penetrating
      keratoplasty. The patient had been initially treated with 1% prednisolone acetate
      ophthalmic suspension and 0.3% gatifloxacin eyedrops to his left eye from the
      first day postoperatively. Three weeks later, the precipitates were more
      numerous, larger, and diffuse in distribution. Gatifloxacin was discontinued and
      substituted with a neomycin-polymixin B-dexamethasone ophthalmic ointment.
      METHODS: A detailed history, physical examination, laboratory workup, and tandem
      scanning confocal microscopy were performed. RESULTS: Tandem scanning corneal
      confocal microscopy confirmed the presence of crystals in the cornea.
      CONCLUSIONS: Gatifloxacin, a fourth-generation fluoroquinolone, can cause
      intrastromal macroscopic crystalline deposits through a compromised corneal
      epithelium, similar to what has been described for ciprofloxacin, a second
      generation fluoroquinolone.

PMID- 15499241
TI  - Pseudomonas aeruginosa corneal binding after 24-hour orthokeratology lens wear.
AB  - PURPOSE: To examine the effect of short-term 24-hr orthokeratology lens (OKL)
      wear on Pseudomonas aeruginosa binding, epithelial surface cell morphology,
      epithelial sheet thickness, and stromal thickness in a rabbit model. METHODS:
      Seventeen New Zealand white rabbits were treated according to the Association for
      Research in Vision and Ophthalmology Statement for the Use of Animals in
      Ophthalmic and Vision Research. Partial membranectomy was performed on all
      rabbits 1 week before the experiments. Baseline values for epithelial and stromal
      thickness and epithelial surface cell size were determined by in vivo confocal
      microscopy in one randomly chosen eye (n = 6). One week later, rabbits were
      fitted in the same eye with a hyper oxygen-transmissible OKL. Twenty-four hours
      later, confocal microscopy was repeated. The second group of rabbits (n = 6) was
      fitted with an OKL in one randomly chosen eye for 24 hr. P. aeruginosa binding to
      the corneal epithelium was assessed for the control corneas and those exposed to
      the test lens. Scanning electron microscopy was performed on a third group of
      rabbits to assess epithelial surface damage (n = 5). RESULTS: There was a
      statistically significant difference (P<0.001) in P. aeruginosa binding between
      the control (1.11 +/- 0.74 x 10(5) colony-forming units per cornea) and the OKL
      wearing eyes (2.74 +/- 0.69 x 10(5) colony-forming units per cornea). The central
      epithelium thinned by 6.5% after lens wear (48.2 +/- 1.9 microm to 45 +/- 1.7
      microm, P=0.005); however, central stromal thickness increased by 7.3% (322 +/-
      22 microm to 345 +/- 29 microm, P=0.006). Compared with the baseline value,
      central epithelial cell size increased significantly from 1,253 +/- 140 mm(2) to
      1,627 +/- 393 mm(2) (29.4%, P=0.02). Scanning electron microscopy showed
      increased surface epithelial damage associated with OKL wear. CONCLUSIONS: This
      prospective, masked, pilot study showed that 24-hr hyper oxygen-transmissible OKL
      wear induced a statistically significant increase in P. aeruginosa binding to the
      epithelium of the rabbit cornea, accompanied by central epithelial thinning,
      stromal thickening, and surface cell damage assessed by scanning electron
      microscopy. Collectively, the data suggest that despite adequate lens oxygen
      transmissibility, the mechanical pressure inherent in the OKL design exerted on
      the corneal surface appears to be associated with increased adherence of P.
      aeruginosa to surface corneal epithelial cells, which may pose an increased risk
      for lens-related microbial keratitis, especially in overnight (i.e., closed-eye)
      wearing conditions. Future studies are needed to determine whether these results
      are similar in human wear and how P. aeruginosa binding during OKL wear compares
      with other lens-wearing modalities, such as daily or continuous soft lens wear.

PMID- 15499242
TI  - Orthokeratology: old devil vs. new saint: the dialogue continues...

PMID- 15499243
TI  - Corneal Refractive Therapy: Challenges, Controversies, and New Opportunities.
      Proceedings form a world summit symposium. April 29-May 1, 2004, Ft. Lauderdale,
      Florida, USA.

PMID- 15499244
TI  - Orthokeratology (corneal refractive therapy): what is it and how does it work?
AB  - This article reviews current knowledge regarding orthokeratology, also known as
      corneal refractive therapy. Modern orthokeratology using reverse-geometry gas
      permeable lenses is an effective procedure for the temporary reduction of low to
      moderate myopia. The use of an overnight lens-wearing protocol provides an
      alternative to refractive surgery for many patients. Onset of the refractive
      effect is rapid, with observable changes within minutes and stability of effect
      after 7 to 10 days of treatment. The procedure appears to be fully reversible on
      cessation of lens wear. The orthokeratology effect is achieved through central
      corneal epithelial thinning and mid peripheral stromal thickening, although the
      cellular basis for these changes requires further research. Because of recent
      reports of severe corneal infections with overnight orthokeratology, the safety
      of the procedure is under active investigation, and it is clear that minimal
      clinical standards must be promulgated internationally to ensure a future for
      this approach to refractive correction.

PMID- 15499245
TI  - Is "whole eye" wavefront analysis helpful to corneal refractive therapy?
AB  - PURPOSE: To examine how corneal refractive therapy (CRT) affects the balance
      between corneal surface and whole eye spherical aberration (Z4) and to identify
      whether corneal aberrations alone can accurately predict optical outcomes of CRT.
      METHODS: Whole eye and corneal spherical aberrations were measured at baseline
      and 1 month after CRT in 12 dilated eyes (baseline myopia range, -2.25 to -6.00
      diopters [D]; mean, -3.23 +/- 1.06D). Whole eye aberrations were measured under
      cycloplegia using a Shack-Hartmann aberrometer, and corneal aberrations were
      measured using Keratron corneal topography elevation maps converted to wavefront
      Zernike polynomials using VOL-CT. Whole eye and corneal surface aberrations were
      scaled for 6-mm pupil diameters. RESULTS: No statistically significant
      correlation existed between corneal and whole eye spherical aberration at
      baseline. Corneal and whole eye spherical aberration increased in all eyes after
      CRT. A statistically significant and moderately positive correlation was found
      between corneal and whole eye spherical aberration after CRT (R = 0.632, P =
      0.004). The linear regression slope was positive (m = +1.449) and indicated that
      whole eye spherical aberration exceeds corneal spherical aberration after CRT.
      CONCLUSIONS: Whole eye wavefront analysis is essential to methods designed to
      optimize visual performance with CRT; results indicate that CRT affects the
      entire optical system and not just the anterior corneal surface. Moreover,
      because CRT-induced whole eye spherical aberration cannot be explained by corneal
      aberrations alone, commonly accepted beliefs that the mechanism of action is
      limited to corneal tissue redistribution may need to be revisited.

PMID- 15499246
TI  - Corneal and epithelial thickness changes after 4 weeks of overnight corneal
      refractive therapy lens wear, measured with optical coherence tomography.
AB  - PURPOSE: To investigate thickness changes of the total cornea and epithelium
      across the horizontal corneal meridian after 4 weeks of overnight corneal
      refractive therapy (CRT) rigid contact lens (Paragon Vision Sciences, Mesa, AZ)
      wear. METHODS: Thirty subjects were fitted with CRT contact lenses (Dk/t = 67),
      which were worn overnight for 4 weeks. Corneal thickness was measured at nine
      locations along the horizontal meridian by using optical coherence tomography
      (OCT) before lens insertion in the evening. Corneal thickness was measured the
      next morning immediately after lens removal and 1, 3, 7, and 14 hours later. This
      was repeated on days 4, 10, and 28 of the study and then 3 days after
      discontinuing lens wear. RESULTS: Twenty-three subjects completed the study. At
      lens removal on day 1, the central and paracentral cornea swelled by 4.9% and
      6.2%, respectively (both P = 0.000). The central epithelium thinned by 7.3%, and
      the mid peripheral epithelium thickened by 13% (both P = 0.000). Corneal swelling
      recovered throughout the day, with most of the deswelling taking place within the
      first 3 hours after lens removal. Maximal central epithelial thinning reached
      13.5% by day 4. Three days after the study completion, corneal and epithelial
      thickness had recovered to baseline values. CONCLUSIONS: This study shows that
      CRT lenses induce differential overnight swelling across the cornea, with rapid
      deswelling during the day. Central epithelial thinning and paracentral thickening
      occurs, with recovery 3 days after discontinuation of lens wear.

PMID- 15499247
TI  - What does overnight lens wear do to the corneal epithelium?: is corneal
      refractive therapy different?
AB  - The corneal epithelium plays a central role in preventing infectious keratitis.
      It is a layer that functions both as a physical barrier and as an active
      component of the ocular surface defense system. Contact lens wear is capable of
      altering the structure and physiology of the corneal epithelium, potentially
      increasing the risk of infectious keratitis. This brief review summarizes the
      effects of continuous contact lens wear and corneal refractive therapy on the
      physiology and structure of the corneal epithelium.

PMID- 15499248
TI  - Histologic and histochemical changes in rabbit cornea produced by an
      orthokeratology lens.
AB  - PURPOSE: To report the histologic and histochemical properties of rabbit cornea
      after insertion of an orthokeratology lens. METHODS: An orthokeratology lens was
      placed on the left corneas of rabbits for 8 hours daily, and their eyes were
      enucleated after 7, 14, 21, and 28 days and examined histologically and
      histochemically. The right eyes were used as controls. RESULTS: After 7-14 days,
      hematoxylin and eosin staining of the cornea revealed that the epithelial layer
      was slightly thinner in the central area and thicker in the intermediate area,
      but its thickness gradually became normal toward the limbus. Periodic acid-Schiff
      staining showed no abnormal distribution of glycogen granules or glycogen
      producing cells. 5-bromo-2-deoxyuridine staining revealed more mitoses in the
      central area than in the intermediate area. Histochemical staining showed lactic
      dehydrogenase activity in the central area of the lens, whereas alkaline
      phosphatase activity and beta-glucuronidase activity were slightly increased in
      the intermediate area. There were no other clearly abnormal findings.
      CONCLUSIONS: The thickness of the corneal epithelium showed topographical
      variation consistent with the effect of orthokeratology. The result of
      histochemical studies suggested that there were no marked alterations in
      epithelial function.

PMID- 15499250
TI  - Endothelial response to overnight corneal reshaping.
AB  - PURPOSE: To discuss corneal endothelial structure during different environments.
      Little information has been available on the structure of the corneal endothelium
      during overnight corneal reshaping. METHOD: Patients were selected to represent
      different environments of contact lens wearing to contrast them to patients who
      changed their environment from contact lens use to overnight corneal reshaping.
      RESULTS: There were no apparent ill effects to the corneal endothelium from
      overnight corneal reshaping. CONCLUSIONS: Corneal endothelial polymegathism and
      pleomorphism can decrease with properly prescribed and monitored overnight
      corneal reshaping lenses over some standard contact lenses.

PMID- 15499251
TI  - How does the cornea change under corneal reshaping contact lenses?

PMID- 15499252
TI  - Overnight corneal reshaping versus soft daily wear: a visual quality of life
      study (interim results).
AB  - PURPOSE: To evaluate patients' perceptions of visual quality of life differences
      in a crossover study with two different modes of contact lens wear: overnight
      corneal reshaping (OCR) lenses and daily-wear soft lenses. METHODS: Qualified
      subjects wore one mode of contact lens for 8 weeks and then completed the
      National Eye Institute RQL-42 questionnaire. After a washout period, subjects
      wore the alternate mode for 8 weeks followed by the questionnaire. During soft
      lens mode, subjects wore lenses during their waking hours. During the overnight
      corneal reshaping mode, subjects wore lenses only while sleeping. Soft lenses
      were Biomedics 55 2-week disposable lenses. OCR lenses were Corneal Refractive
      Therapy (CRT) lenses by Paragon. Subjects were randomly assigned to wear soft
      contact lenses or OCR lens first. After completing both phases of the study,
      patients were asked to choose which mode they preferred. RESULTS: Interim results
      show that of 74 subjects enrolled, 45 have completed both phases; 14 have dropped
      out of the study; and 15 are still in process. Of the 45 subjects completing both
      phases, 32 have chosen to continue with the CRT lenses, and 13 have chosen to
      stay with the soft lenses. Logarithm of the minimum angle of resolution visual
      acuity was 0.06 (20/20) for soft contact lenses and 0.11 (20/25) for CRT lenses.
      RQL-42 scoring for overall satisfaction was 81.33 for OCR lenses and 74.67 for
      soft lenses. CONCLUSIONS: Although overall satisfaction scores and vision were
      comparable between the two modes, 71% of the subjects elected to stay with CRT
      lenses. In this study of patients who experienced both modes of lens wear, 71%
      chose OCR lenses.

PMID- 15499254
TI  - Is corneal refractive therapy a new modality whose time has come or repackaged
      orthokeratology whose time has passed?: a view from an experienced corneal
      clinician.
AB  - I was asked to evaluate corneal refractive therapy (CRT) as an experienced
      ophthalmologist, who is a corneal specialist. I reviewed the literature and
      listened to and talked with ophthalmologists, optometrists, and researchers using
      and studying CRT. I feel that CRT is safe and effective. It offers a nonsurgical
      option for patients who are not eligible for surgery, particularly because of
      age, or for those who want to correct myopia for daytime vision but do not want
      to have surgery or wear a contact lens. CRT can be a valuable option to provide
      patients in a refractive surgery practice.

PMID- 15499255
TI  - Myopia reduction using corneal refractive therapy contact lenses.
AB  - PURPOSE: The Paragon corneal refractive therapy (CRT) lens provides a temporary
      reduction in myopia by molding the cornea while sleeping. This study presents our
      initial experience in 20 patients fit with the CRT lens. METHODS: Myopic patients
      with a spherical correction between -1.00 and -7.75 diopters (D) and astigmatism
      less than 1.62 D were fit and followed for an average of 5.1 months. RESULTS:
      Patients whose initial refraction was between -1.00 and -3.00 D achieved an
      average of 1.50 D myopic correction; those between -3.25 and -6.00 achieved an
      average of 2.9 D myopic correction; and those greater than -6.00 D averaged 5.8 D
      of correction. Uncorrected visual acuity improved an average of 7.7 lines. One
      hundred percent achieved 20/40 or better vision, and 55% achieved 20/20 vision.
      Fifty-five percent were within 0.50 D of plano, and 84% were within 1.00 D of
      plano. There was an overall 80% success rate. CONCLUSIONS: The CRT lens is an
      effective modality for temporary myopic correction for a restricted subset of
      myopic candidates. Those with a spherical manifest refraction between -1.00 and 
      6.00 D and up to 1.50 D of astigmatism can expect a good outcome with these
      lenses.

PMID- 15499256
TI  - Study design issues in a corneal reshaping contact lens myopia progression study.
AB  - Advances in contact lens design have led to corneal reshaping contact lenses that
      can be worn at night to temporarily reduce myopia so that patients can see
      clearly without glasses or contact lenses. Children are able to wear corneal
      reshaping contact lenses, but we do not know how they may affect the progression
      of myopia. A myopia control study with corneal reshaping contact lenses poses
      study design problems that other studies do not encounter because they
      temporarily reduce the refractive error. A discussion of the choice of primary
      outcome and control group will highlight some of these unique study design
      issues.

PMID- 15499259
TI  - Quality of vision with corneal refractive therapy.

PMID- 15499258
TI  - Adverse corneal events associated with corneal reshaping: a case series.
AB  - PURPOSE: This case series presents the first documented cases of infectious
      ulcers associated with overnight orthokeratology in North America and other less
      serious complications associated with overnight corneal reshaping. CASE REPORTS:
      Five cases of adverse corneal events associated with corneal refractive therapy
      are described: two cases of microbial keratitis, one case of infiltrates, one
      case of toxic keratitis, and one corneal abrasion. CONCLUSIONS: Corneal
      compromise and poor compliance can cause adverse events with corneal reshaping.
      The need for ongoing patient education is important not only for pediatric
      contact lens patients, but also for adults.

PMID- 15499260
TI  - Corneal refractive therapy and the corneal surface.

PMID- 15499261
TI  - Corneal refractive therapy, uncorrected visual acuity, and "E" values: personal
      experiences.
AB  - PURPOSE: The author describes selected aspects of his clinical experience in
      fitting and prescribing orthokeratology lenses to temporarily reduce or eliminate
      myopia. The precision of videokeratography (VK) data in determining corneal
      sagittal depth is examined. Treatment outcomes are analyzed after overnight wear
      of two proprietary corneal remodeling systems. Two case reports describing off
      label treatments are presented. METHODS: A retrospective analysis was performed
      of the baseline VK data of 25 consecutive candidates (50 eyes) for corneal
      remodeling, captured with a Keratron topographer. Sixteen consecutive patients
      fitted with Paragon corneal refractive therapy (CRT) lenses were compared against
      an age- and sex-matched group of patients fitted with the Mountford BE lens for 1
      day, 1-week, and 1-month uncorrected visual acuity. RESULTS: The mean +/- SD of
      the apical radius ("Ro") and corneal eccentricity ("E") values was 0.03 +/- 0.01
      mm and 0.03 +/- 0.01 degrees , respectively, indicating a spread of 24 microm in
      the sagittal elevation data. Mean target myopia and 1-day uncorrected visual
      acuity were -1.71 +/- 0.71 diopters and 20/20 +/- 20/0.86, respectively, for the
      Paragon CRT lenses and -2.30 +/- 0.89 diopters and 20/31 +/- 20/20.6,
      respectively, for the Mountford BE lenses. CONCLUSIONS: The Paragon CRT and the
      Mountford BE lenses delivered impressive reductions in uncorrected visual acuity
      after the first night of overnight wear. The Paragon CRT lens had the advantage
      of not requiring a previous overnight lens trial before commencing the treatment
      program.

PMID- 15499263
TI  - The myopia epidemic: is there a role for corneal refractive therapy?

PMID- 15499264
TI  - Recovery of refractive error after corneal refractive therapy.
AB  - PURPOSE: To describe the regression of treatment (i.e., return toward baseline
      refractive error findings) after treatment with corneal refractive therapy (CRT).
      METHODS: After 6 to 9 months of treatment by a standardized protocol for CRT
      (application of high-Dk, proximity control, return zone contact lenses for
      overnight reduction of myopia), refractive error was measured within hours after
      awaking and at 8, 24, 48, and 72 hours. Comparison of regression is analyzed in
      four categories of achieved treatment. Logarithm of the minimum angle of
      resolution visual acuity regression was also measured. RESULTS: In general,
      refractive error returns to baseline after CRT for all measured ranges of
      refraction in the period of measurement of this study. CONCLUSIONS: The greater
      the magnitude of CRT treatment, the more rapid the recovery is to baseline
      refraction.

PMID- 15499265
TI  - Will higher-Dk materials give better corneal refractive therapy results and fewer
      complications?
AB  - PURPOSE: To evaluate the current status of materials in use for corneal
      refractive therapies. METHODS: The most up-to-date data available on rigid gas
      permeable (RGP) lenses, corneal swelling, and corneal infection are reviewed.
      RESULTS: Despite 125 Dk/t units or greater, studies have shown differences in
      overnight swelling between RGP and silicone hydrogel materials. There is a small
      but significant overnight swelling with RGP lenses in this class when compared
      with silicone hydrogels, yet studies of Pseudomonas adherence to human epithelium
      have shown that RGP-wearing corneas bind the least bacteria. CONCLUSIONS: Corneal
      refractive therapies are on the verge of international acceptance as a standard
      alternative for treating refraction. Continually using newer, more permeable lens
      materials is a necessity to ensure safety, efficacy, and, in turn, long-term
      acceptance.

PMID- 15499266
TI  - Overnight orthokeratology: refractive and corneal recovery after discontinuation
      of reverse-geometry lenses.
AB  - PURPOSE: To determine the refractive and corneal topographic recovery after the
      use of reverse-geometry contact lenses for overnight orthokeratology. METHODS:
      Both eyes of 15 subjects were fitted with reverse-geometry contact lenses that
      were worn by the subjects for 1 month. Uncorrected visual acuity, refractive
      correction (sphere and spherical equivalent), corneal curvature, and corneal
      thickness were measured during this time and for 2 weeks after discontinuation of
      lens wear. RESULTS: Ten subjects completed the investigation. Uncorrected visual
      acuity, refractive correction, and corneal curvature had changed significantly (P
      = 0.01) after 1 month of lens wear. By the end of 1 month, central corneal
      thickness was significantly thinner than the baseline value (P = 0.01), but it
      recovered fully after one night of no lens wear. Recovery of corneal curvature
      was complete 1 week after lens wear was discontinued. Refractive correction and
      binocular uncorrected visual acuity recovered fully after 2 weeks. Monocular
      uncorrected visual acuity remained significantly (P = 0.01) different from
      baseline acuity 2 weeks after lens discontinuation. CONCLUSIONS: Full effect of
      overnight orthokeratology in low myopes is achieved within 1 week of initiating
      use of reverse-geometry lenses. Recovery after short-term use of reverse-geometry
      lenses is rapid for corneal thickness and corneal curvature. Refractive
      correction and binocular uncorrected visual acuity recovered fully after 2 weeks.
      Monocular uncorrected visual acuity was the slowest to recover and had not
      achieved full recovery after 2 weeks.

PMID- 15499270
TI  - [Ocular tolerance of a new formulation of nonpreserved diclofenac].
AB  - AIM: To compare the ocular tolerance of nonpreserved diclofenac versus thiomersal
      preserved diclofenac in healthy volunteers. MATERIALS AND METHODS: Forty healthy
      volunteers instilled Dicloabak in the randomised eye and thiomersal-preserved
      diclofenac in the other eye, according to a strictly identical dosing regimen,
      for 28 days. Each volunteer thus served as his or her own control. The dose
      regimen was five drops/day for 7 days followed by three drops/day for 20 days.
      Ocular tolerance was assessed by the discomfort upon instillation (measured on a
      visual analogue scale [VAS]), subjective ocular symptoms following instillation
      (irritation/burning/stinging, eye dryness and foreign body sensation) and finally
      by an objective examination of the ocular surface. These criteria were evaluated
      on days 0, 14, 21 and 28. RESULTS: The subjective ocular symptoms following
      instillation were significantly lower in the nonpreserved group at Day 7 and
      nearly significantly lower until the end of the study. The biomicroscopy exam
      confirmed that there was better tolerance without thiomersal. There was less
      follicular-papillary conjunctivitis and a significantly better lissamine green
      score in the Dicloabak group. CONCLUSION: The results of this study demonstrate
      that the nonpreserved formulation of diclofenac is better tolerated by the ocular
      surface and thus constitutes a therapeutic benefit.

PMID- 15499271
TI  - [Phototherapeutic keratectomy in the treatment of lattice corneal dystrophy type
      I].
AB  - PURPOSE: Lattice corneal dystrophy type I is an autosomal dominant corneal
      dystrophy caused by allelic mutations of the BIGH3 gene. Type I dystrophy is
      recognized clinically by the characteristic net of linear opacities within the
      corneal stroma that results from an accumulation of amyloid. This study was
      designed to evaluate the therapeutic potential of phototherapeutic keratectomy
      (PTK) for the treatment of lattice corneal dystrophy type I. PATIENTS AND
      METHODS: PTK was performed with the Chiron Technolas Chiron Keracor 217c on a
      series of 19 eyes of 13 patients with lattice dystrophy type I. Mean patient age
      was 38.9 years. The mean follow-up period was 36 months. Localization of central
      opacities was determined by analyzing Scheimpflug images. The changes in
      spherical equivalent and best corrected visual acuity were evaluated at 1, 3, 6,
      9, 12, 18, 24 and 36 months. RESULTS: The central depth of the deposits measured
      with the Scheimpflug camera was on average 74.14+/-31.03 microm in the primary
      dystrophies and 30.1+/-10 microm in graft recurrence. We noted a clear
      improvement in visual acuity, which increased by 0.257+/-0.120 to 0.600+/-0.178
      as of the 3rd month and stabilized at 0.684+/-0.257 until the 36th month. A
      disappearance of repeating ulcerations was observed at month 30. We found a
      statistically significant correlation (R=0.6776; p=0.0109) between the
      improvement in vision (in lines) and the depth of opacities (with the Scheimpflug
      camera). The mean hyperopic shift caused by photoablation (69+/-15 microm) was
      +0.71+/-1 D at 36 months. CONCLUSION: These results confirm that PTK is an
      effective method of managing corneal lattice dystrophy type I.

PMID- 15499272
TI  - [Lasik, PRK and quality of vision: a study of prognostic factors and a
      satisfaction survey].
AB  - PURPOSE: To confirm the clinical interest of pupillary diameter measurement for
      selecting indications and determining surgical protocols, to look for clinical
      factors predisposing to night vision symptoms, and to the assess patient
      satisfaction level for photoablation techniques not based on aberrometry.
      METHODS: This retrospective study was conducted on 111 consecutive myopic
      patients (219 eyes, with a mean spherical equivalent of -4.25+/-1.84 D); they
      underwent Lasik (91.3% of cases) or photorefractive keratectomy, after having
      their pupillary diameter measured by the Colvard pupillometer. Clinical data were
      collected from medical files, and an anonymous questionnaire was sent in order to
      assess quality of vision and postoperative satisfaction. RESULTS: Preoperative
      aims were reached (r=0.41, p<0.0001). The response rate for the questionnaire was
      81.1%. Daytime vision was the same or better for 91.1% of the patients, but 25.6%
      had worse night vision than before. Night vision symptoms were mentioned by 46.7%
      of the patients, and the most frequent complaint was halos. However, 97.8% of the
      patients declared themselves as satisfied and would recommend such surgery to
      their family and friends. A preoperative myopia greater than 4.50D (RR=1.52,
      p<0.05) and a postoperative keratometry greater than 8.44 mm (RR=1.62, p<0.05)
      were risk factors for having night vision symptoms, but pupillary diameter was
      not a risk factor. CONCLUSION: This survey gives an indirect confirmation of the
      interest of scotopic pupillary diameter measurement and taking it into account in
      photoablation protocols. However, night vision symptoms remain frequent but do
      not influence patient satisfaction. Knowledge of risk factors and technical
      progress should provide a better quality of vision after Lasik.

PMID- 15499273
TI  - [The relationship between keratoconus and axial myopia].
AB  - PURPOSE: To study the relationship between keratoconus and axial myopia. METHODS:
      We prospectively studied refraction and ocular biometry in 100 consecutive
      keratoconus eyes, and 100 emmetropic eyes. Biometric data (including posterior
      segment length) were obtained by A-scan ultrasound, Orbscan, and ultrasonic
      pachymetry. Biometric measurements were compared in both groups. RESULTS:
      Anterior chamber depth, posterior segment length and axial length were
      significantly different between the two groups (p<0.001). Axial length was
      significantly greater in the keratoconus group than in the emmetropic group
      (23.97 mm versus 23.21 mm, p<0.001). Posterior segment length was significantly
      greater in the keratoconus group than in the emmetropic group (16.54 mm versus
      15.99 mm, p<0.001). In the keratoconus group, the posterior segment length and
      the subjective spherical equivalent were significantly correlated (rs=-0.45,
      p<0.001). CONCLUSION: The increase in posterior segment length in the keratoconus
      group and the correlation between posterior segment length and spherical
      equivalent in the keratoconus group suggest a statistical relationship between
      keratoconus and axial myopia.

PMID- 15499274
TI  - [Accuracy of videokeratographic quantitative criteria for detection of
      keratoconus suspects in families with keratoconus].
AB  - AIM: We statistically assessed the videokeratographic data obtained from families
      with keratoconus in order to determine reliable criteria for detecting
      keratoconus suspects. MATERIAL AND METHODS: Fourteen keratoconus patients from 12
      families were enlisted. We investigated 55 relatives (110 eyes). Standard
      videokeratographic data were obtained by screening 30 individuals (60 eyes) with
      clinically normal eyes, with no history of ocular disorders, contact lens wear,
      or keratoconus individuals in their family. Videokeratographic qualitative and
      quantitative analyses were performed on every subject. The videokeratographic
      threshold values obtained from the control group were used as a reference.
      RESULTS: Two criteria based on the Klyce/Maeda indices proved their statistical
      significance in detecting keratoconus suspects. When considering the significant
      criteria ascertained by the statistical analysis, building pedigrees favored the
      autosomal dominant mode of inheritance. Two of the pedigrees corresponded to
      either a recessive mode of transmission or the potential occurrence of a de novo
      mutation. CONCLUSION: We have determined videokeratographic criteria of
      statistical significance for detecting keratoconus suspects. The knowledge of the
      status of each member of families with keratoconus is a prerequisite to
      performing genetic linkage analyses, which may allow a precise locus linked with
      this disorder to be refined.

PMID- 15499275
TI  - [Keratoconus: what happens with older patients?].
AB  - INTRODUCTION: Keratoconus is a degenerative corneal disease that is most often
      seen in young patients. The object of the present study was to analyze the
      demography of keratoconus patients. PATIENTS AND METHODS: We conducted a
      prospective study at Bordeaux University Hospital from January 2001 to September
      2001. The study included all the consecutive patients with a diagnosis of
      keratoconus, detected previously or during the current examination. Inclusion
      criteria included evidence of unilateral or bilateral abnormal corneal steepening
      with videotopography. RESULTS: We included 121 patients. The results showed a
      mean age of 33.4 years in males and 37.1 years in females. The number of patients
      older than 50 was low: 3 out of 83 (3.6%) males and 6 out of 38 (15.7%) females.
      CONCLUSION: Two hypotheses on the low number of older patients can be suggested.
      1) Keratoconus, which is a collagen disorder of the corneal stroma, may be
      associated with other undetected systemic diseases, which could induce premature
      death. Different studies have suggested a relationship between keratoconus and
      mitral valve prolapse. In this case, we can propose preventive treatment. 2)
      These patients, who have been informed of the nature and the therapeutical
      modalities of their disease, no longer consult at the hospital, but are followed
      by their local ophthalmologists.

PMID- 15499276
TI  - [Femtosecond laser: a micromachining system for corneal surgery].
AB  - INTRODUCTION: The authors present the diode-pumped, all-solid state,
      neodymium:glass femtosecond laser from the Laboratory of Ocular Biotechnology,
      Hotel-Dieu Hospital. MATERIALS AND METHODS: We worked with a 1,065-nm wavelength
      infrared laser. This laser is composed of an oscillator and amplification glass
      matrix mixed with neodymium. Its stretching and compression system is capable of
      producing pulses lasting a few hundred femtoseconds. The repetition rate is
      adjustable, ranging from 1 to 10 kHz, and can reach energies up to 60 microJ. The
      delivery system was set up on an optical table, with human corneal samples fixed
      to an anterior chamber system, which can be moved over the X-Y-Z axis by a
      computer-guided translation motor with micrometric precision. We analyzed the
      biological effects of laser impacts in human corneal tissue, obtained from the
      French Eye Bank. RESULTS: The femtosecond laser provides automated corneal
      cutting with a high level of precision, which can be verified on the corneal
      surface regularity by scanning electron microscopy analysis. Silicon samples can
      also be cut and can be used for calibration testing of the laser. CONCLUSION: The
      set-up composed of the femtosecond laser and the described delivery system enable
      precise corneal cutting and offer the opportunity to study its characteristics.

PMID- 15499277
TI  - [Role of vitrectomy in patients with a decrease in visual acuity secondary to
      asteroid hyalosis].
AB  - PURPOSE: Asteroid hyalosis is a vitreous degeneration with calcium and phosphorus
      -lipid complexes in elderly patients with vascular risk factors or general
      disease such as diabetes mellitus. Synchysis scintillans is a complication of
      pathological eyes. Generally there are no symptoms. This study aims to evaluate
      the role of vitrectomy in patients with a decrease in visual acuity. CASE
      REPORTS: Pars plana vitrectomy was performed in three patients with visual acuity
      less than 1/10. The biomicroscope examination showed white and bright particles
      with rounded and variable shapes localized in the anterior vitreous, moving with
      the eye. The visualization of the fundus was difficult or impossible. On
      echography B, the vitreous was very dense with a complete posterior vitreous
      detachment. The vitrectomy was completed in one case by peeling an epiretinal
      membrane. Visual acuity was improved for two patients (6/10 or more) and stable
      for one patient with an atrophic DMLA. DISCUSSION AND CONCLUSION: These results
      were compared with studies in the literature: in spite of complications,
      vitrectomy can be indicated in patients with a substantial decrease in visual
      acuity. However, the result is conditioned by the macular status. Fluorescein
      angiography can, when it is possible, evaluate the fundus before surgery.

PMID- 15499278
TI  - [Bilateral acute retinal necrosis syndrome associated with meningoencephalitis
      caused by herpes simplex virus 2. A case report].
AB  - INTRODUCTION: Acute retinal necrosis syndrome (ARN syndrome) is a rare viral
      disease with a poor prognosis in most cases. It is characterized by substantial
      ocular inflammation with progressive retinal necrosis, occlusive vasculitis and
      sometimes extraocular features. CASE REPORT: We report the case of a 62-year-old
      woman who was referred for a suspicion of a stroke. Ophthalmological examination
      revealed a profound bilateral visual loss due to extensive retinal necrosis. The
      patient was immediately treated with antiherpetic drugs. ARN syndrome with
      meningoencephalitis caused by herpes simplex virus type 2 was confirmed by PCR
      studies performed on aqueous humor and cerebrospinal fluid. Herpes simplex virus
      2 (IgG+ , IgM-) was probably reactivated after intrathecal injection of steroids
      because of pain associated with narrowing of the lumbar vertebral canal. The
      patient was treated with intravenous Acyclovir for 3 weeks. After 4 months, both
      retinas were detached. DISCUSSION AND CONCLUSION: ARN syndrome caused by herpes
      simplex virus 2 most often occurs after reactivation of the latent virus in
      patients with a neurological medical history or congenital infection. Antiviral
      treatment must begin early to decrease risks of bilateralization and
      complications.

PMID- 15499279
TI  - [A case of a retinitis pigmentosa and asteroid hyalosis].
AB  - Asteroid hyalosis is a rare degenerative condition of the vitreous. No causal
      relationship between retinitis pigmentosa and asteroid hyalosis has been
      established. We report a case of a 65-year-old male admitted for progressive
      hemeralopia. Visual acuities were 2/10e in the right eye and 4/10e in the left
      eye. Ophthalmic examination revealed a large number of asteroid and refringent
      bodies, a typical retinitis pigmentosa with a cystoid macular oedema confirmed by
      fluorescein angiography. Electrodiagnostic testing revealed an altered
      electroretinogram. Visual fields showed a typical generalized constriction. We
      discuss the clinical aspects and physiopathogenic mechanisms of this rare
      association through this case and other cases found in the literature.

PMID- 15499281
TI  - [Thyroid-associated ophthalmopathy: physiopathology, endocrine status].
AB  - The pathogenesis of Graves' ophthalmopathy remains uncertain. An inflammatory
      reaction is well established in orbital tissues in Graves' thyrotoxicosis. This
      inflammation is associated with antithyroid antibody action, but is not
      systematic in autoimmune hyperthyroidism patients. If ocular manifestations are
      pathognomonic for Graves' disease they can present in association with
      euthyroidism or hypothyroidism. Ophthalmopathy factors could be genetically
      determined but environmental parameters such as smoking and stress may also be
      involved, supporting the hypothesis that the autoimmune process in this ocular
      inflammation could be modulated in each patient based on personal and
      environmental factors.

PMID- 15499282
TI  - [Clinical signs of dysthyroid orbitopathy].
AB  - Dysthyroid ophthalmopathy is an inflammatory disease of the orbit, combined or
      not with thyroid disorders. However, pure ophthalmologic forms exist, and the
      diagnosis can be made by the ophthalmologist. The diagnosis is made by examining
      eyelid malposition, oculomotor disorders, inflammatory signs, proptosis
      measurement, and by the search for optic nerve pain. We discuss the NOSPECS
      classification, which can evaluate the severity and progression of the disease.

PMID- 15499283
TI  - [Dysthyroid orbitopathy: imaging].
AB  - Computed tomography and magnetic resonance imaging are useful tools for assessing
      orbital content. Using these imaging modalities, one can quantify orbital
      involvement in Graves disease. This analysis is based upon five items: proptosis,
      fat, muscles, optic nerve and ethmoid.

PMID- 15499284
TI  - [Complications of dysthyroid ophthalmopathy].
AB  - The complications of dysthyroid ophthalmopathy should be known and screened in
      every patient since they can worsen visual prognosis and are critical to the
      decision for treatment. Ocular surface alteration can result from eyelid
      malposition, blinking deficiency, eye dryness, and proptosis. Oculomotor
      disorders are detected by coordimetry or a forced duction test. Optic neuropathy
      can be compressive or glaucomatous. Intraocular pressure elevation can result
      from elevation of intraorbital pressure, indentation by an enlarged muscle, or
      increased backflow in episcleral veins.

PMID- 15499285
TI  - [Medical treatment of dysthyroid orbitopathy].
AB  - The majority of Graves' patients have mild and nonprogressive ocular involvement
      that does not require aggressive treatment. Local supportive measures such as
      wearing tinted lenses, proper eyelid hygiene, and the use of wetting agents or
      gels are usually sufficient to obtain symptomatic relief until eye disease
      becomes inactive. Smoking must be stopped and euthyroidism controlled. Management
      of severe forms (10% of patients) is often difficult and does not provide
      consistently favorable results. The use of glucocorticoids is a well-established
      method of treatment, indicated in severe inflammatory forms as well as in
      complicated forms of optic neuropathy, ocular hypertension, and corneal exposure,
      and are used orally or intravenously, at high doses and for prolonged periods of
      time. Prisms are useful in cases of diplopia. Favorable effects are reported in
      slightly more than 60% of cases. Glucocorticoids can be combined with orbital
      radiotherapy in patients with severe orbitopathy.

PMID- 15499286
TI  - [The role of radiotherapy in Graves' ophthalmopathy].
AB  - Radiotherapy is a well-established method of treatment for Graves'
      ophthalmopathy. The main rationale is its anti-inflammatory effect and the high
      radiosensitivity of T lymphocytes and orbital fibroblasts, which are important
      effectors in the immune reactions characterizing this disorder. Most centers use
      a dose of 20 Gy, ten daily doses of 2 Gy given over a period of 2 weeks. Overall
      favorable responses have been reported in 60% of cases. The best responses were
      noted for inflammatory signs and recent onset of extraocular muscle involvement.
      Radiotherapy is well tolerated and safe. A careful selection of patients is
      necessary. New randomized studies will have to evaluate new radiotherapy
      protocols with or without corticosteroids or medical immunosuppression.

PMID- 15499287
TI  - [Orbital decompression for dysthyroid orbitopathy: a review of techniques and
      indications].
AB  - Orbital bony decompression has a definite place in the management of severe
      manifestations of dysthyroid orbitopathy such as optic neuropathy, exposure
      keratitis, and exophthalmos. This surgical procedure can be undertaken when
      medication and radiation therapy fail. Esthetic and functional results are
      globally satisfying and explain the interest taken in this technique. This
      article will describe the development of this procedure and will outline the
      surgical techniques and their complications. It emphasizes the multifactor
      indications for this procedure.

PMID- 15499288
TI  - [Orbital fat decompression techniques].
AB  - Fat removal orbital decompression (FROD) was first described by Olivari in 1988.
      Through a blepharoplasty approach, fat pads from the five palpebral pockets, as
      well as intraconal fat, are carefully removed. The main complications are
      retrobulbar hemorrhage and postoperative diplopia. The best indications are
      patients with wide orbits without compressive optic neuropathy. FROD is an
      inescapable procedure in a balanced approach to surgical orbital decompression.

PMID- 15499290
TI  - Medical ethics, clinical research, and special aspects in nuclear medicine.
AB  - Medical ethics is the science of survival. It studies the working out of
      judgments on right or wrong referred to the human being as a biological entity
      interacting with the whole ecosystem. Medical ethics in clinical research raises
      numerous moral and technical issues. Methodological aspects are essential for
      carrying out the aim of clinical research. Medical ethics documents are inspired
      by the Nuremberg Code and culminate in the recently updated Helsinki Declaration
      of 1964. In Italy 2 ministerial decrees in 1997 and 1998 laid the basis for the
      work of a medical ethics committee. They acknowledge the European Good Clinical
      Practice Guidelines and set professional needs within ethical committees. In
      clinical research the use of ionising radiation merits special consideration. In
      the recent past, serious human rights abuses in radiation experiments of the
      1950s and 1960s have been found. As regards research in this field we can refer
      to the publication of the International Commission on Radiological Protection
      (ICRP) and to the report of the World Health Organisation (WHO). Legislative
      decree no. 187 of May 26, 2000, which transposed the 97/43/ EURATOM Directive
      represents the most comprehensive and recent normative reference to clinical
      research using ionising radiation. However, law no. 39 of March 1, 2002 is
      important for the partial modifications of previous decrees (art. 108 of L.D. no.
      230 of March 17, 1995 and, art. 4 and attachment III of L.D. no. 187 of May 26).
      In this paper medical ethics, research, methodological issues and aspects of
      ionizing radiation are discussed.

PMID- 15499291
TI  - Myocardial SPECT: what do we gain from attenuation correction (and when)?
AB  - AIM: This study aimed at assessing the impact of attenuation correction performed
      by means of a new hardware device (Beacon(tm)) in the assessment of coronary
      artery disease with myocardial SPECT and, afterwards, at identifying what
      specific risk class of patients would mostly benefit from the technique. METHODS:
      The first 500 consecutive patients, referred to our facility for coronary artery
      disease (CAD) assessment, were included in this study. Myocardial SPECT was
      performed after i.v. of 740 MBq of (99m)Tc Tetrofosmin (Myoview, Amersham Health)
      both after stress and at rest. Studies were acquired by means of a 3 head system
      (IRIX, Philips Medical System) equipped with the Beacontm option to correct for
      non-uniform attenuation. Out of the whole population studied, 130 patients
      underwent coronary angiography (CAG), 108 of which were proven to be affected by
      significant CAD, defined as a >50% coronary vessel lumen reduction. Attenuation
      corrected (AC) as well as non-attenuation corrected studies (NAC) were
      reconstructed, blindly read and qualified as: normal; borderline normal;
      borderline abnormal and definitely abnormal. RESULTS: In the group of 130
      patients who underwent CAG, sensitivity for CAD detection did not vary
      significantly (96% and 93%, for NAC and AC studies, respectively, p=ns) whereas
      specificity increased from 73% (NAC studies) to 91% (AC studies), p<0.01.
      Normalcy rate, assessed in a small subgroup (n=21) with a <5% likelihood for CAD,
      was found to be 80% for NAC studies vs 93% for AC studies (p<0.05). As regards
      synthetic clinical judgements, when we grouped normal and probably normal
      readings into a single ''normal'' category and, conversely, probably abnormal and
      definitely abnormal into a single ''pathological'' category, we see that after
      attenuation correction studies reported as ''pathological'' are reclassified as
      ''normal'' in 17.8% of the cases (25.2% in males and 6.9% in females, p<0.05).
      The opposite is seen in only 1.6% of the cases (1.3% in males and 4.4% in
      females). According to established criteria, 155 patients were classified at low
      risk for CAD (<15%), 115 at intermediate risk (from >15% to <50%) and 230 at high
      risk (>50%). The intermediate risk class showed the greatest impact: ''normal''
      findings increased from 52% to 72%, thus reducing the rate of ''pathological''
      reports from 48% to 28%. CONCLUSIONS: This study shows that, while sensitivity
      for CAD is not affected by attenuation correction, specificity increases
      significantly, as well as normalcy rate. Out of the whole population studied, the
      main finding was that attenuation correction increases the rate of normal
      reports, more frequently in males than in females, and that studies carried out
      in patients at intermediate risk for CAD are more likely to be affected.

PMID- 15499292
TI  - Imaging characterization of non-hypersecreting adrenal masses. Comparison between
      MR and radionuclide techniques.
AB  - AIM: In patients with non-hypersecreting adrenal masses, tumor characterization
      is clinically relevant to establish the appropriate treatment planning. The aim
      of this study was to comparatively characterize such adrenal lesions using MR and
      radionuclide techniques. METHODS: Thirty patients with non-hypersecreting
      unilateral adrenal tumors underwent both MR and adrenal scintigraphy. MR was
      performed using SE T1- (pre- and post-gadolinium DTPA) and T2-weighted images as
      well as in- and out-phase chemical-shift imaging (CSI). MR qualitative and
      quantitative (signal intensity ratios) evaluation was performed. Radionuclide
      studies consisted of iodine-131 nor-cholesterol (n=20), iodine-131 MIBG (n=15)
      and fluorine-18 FDG PET (n=11) scans. Histology (n=16), biopsy (n=3) or clinical
      imaging follow-up (n=11) demomstrated 13 adenomas, 3 cysts, 2 myelolipomas, 4
      pheochromocytomas (pheos), 4 carcinomas, 1 sarcoma and 3 metastases. Comparative
      imaging analysis was focused on adenomas, pheos and malignant tumors. RESULTS:
      Qualitative MR evaluation showed: signal T2-hyperintensity in 46% of adenomas and
      in 100% of pheos and malignant tumors, no gadolinium enhancement in 92% of
      adenomas and definite signal intensity loss on CSI in 100% of such tumor lesions,
      gadolinium enhancement in 100% of pheos and in 63% of malignancies and no
      absolute change of signal intensity on CSI in 100% of both pheos and
      malignancies. Quantitative MR analysis demonstrated: significantly higher signal
      T2-hyperintensity of pheos compared to adenomas and malignancies as well as
      significantly higher enhancement after gadolinium in pheos compared to adenomas
      and malignancies (p<0.03). Radionuclide studies showed significantly increased
      nor-cholesterol uptake only in adenomas (n=13), significant MIBG accumulation
      only in pheos (n=4) and FDG activity only in malignant adrenal lesions (n=8).
      CONCLUSION: MR techniques may provide some presumptive criteria to characterize
      non-hypersecreting adrenal masses, such as no gadolinium enhancement and definite
      signal intensity loss on CSI in adenomas or quantitatively measured T2
      hyperintensity and gadolinium enhancement in pheos. On the other hand,
      radionuclide modalities offer more specific findings in this setting since nor
      cholesterol and MIBG scans are respectively able to reveal benign tumors such as
      adenoma and pheochromocytoma, while FDG imaging allows identification of
      malignant adrenal lesions. Adrenal scintigraphy is recommended in those patients,
      when MR images are uncertain or inconclusive.

PMID- 15499294
TI  - Should lidocaine be avoided for local anesthesia in radiation synovectomy?
AB  - AIM: Leakage is of major concern when performing radiation synovectomy. Although
      post-treatment immobilization was provided, extra-articular leakage of
      radioactivity has occasionally been observed in patients receiving local
      anesthesia in the course of radiation synovectomy. This study was performed to
      uncover any unfavourable effect of lidocaine on stability of (166)Ho-FHMA (ferrum
      hydroxide macroaggregate). METHODS: The radiopharmaceutical was investigated in
      bovine serum albumin (BSA) solutions (5, 10 mg/ml) at pH 6, 7 and 8. Furthermore,
      the tracer was incubated for 0, 2, 24, 48 and 120 hours in synovial fluid. In
      both series the influence of lidocaine-HCl 2% (500, 1000 microl) has been
      evaluated. RESULTS: In BSA test solutions, amount of lidocaine added [df(2),
      F=7.82, p-level: 0.00] and pH [df(2), F=7.82, p-level: 0.00] significantly
      influenced in vitro stability of (166)Ho labeled FHMA (n=72). This finding was
      confirmed in synovial fluid [df(2), F=3.82, p-level: 0.03] (n=60). CONCLUSION: In
      an experimental design mimicking normal and inflammatory conditions in the joint,
      addition of a few milliliters of lidocaine-HCl followed by a shift towards lower
      pH-values in synovial fluid may endanger stability of the carrier-tracer complex
      (166)Ho-FHMA and thereby enhance extra-articular leakage.

PMID- 15499293
TI  - Iodine-123-vascular endothelial growth factor-165 (123I-VEGF165).
      Biodistribution, safety and radiation dosimetry in patients with pancreatic
      carcinoma.
AB  - AIM: Imaging with radiolabelled vascular endothelial growth factor (VEGF) has
      been developed for the localisation and diagnosis of a variety of human solid
      tumors including gastrointestinal tumors. METHODS: In this study we investigated
      the biodistribution, safety and absorbed dose of iodine-123 radiolabelled
      VEGF(165) ((123)I-VEGF(165)) in 9 patients with pancreatic carcinoma. Following
      intravenous administration of (123)I-VEGF(165) (189+/-17 MBq; <130 pmole (<5
      microg) VEGF(165) per patient), sequential images were recorded during the
      initial 30 min PI. Serial whole-body images were acquired in anterior and
      posterior views at various time points. All patients underwent single-photon
      emission tomography (SPET) imaging. Dosimetry calculations were performed on the
      basis of gamma camera data. Estimates of radiation absorbed dose were calculated
      using the MIRDOSE 3 program. RESULTS: The highest absorbed organ doses were found
      to be thyroid (0.058+/-0.004 mGy/MBq), spleen (0.046+/- 0.017 mGy/MBq), urinary
      bladder (0.04+/-0.02 mGy/MBq), lungs (0.034+/-0.009 mGy/MBq) and kidneys (0.033+/
      0.005 mGy/MBq). The effective dose was estimated to be 0.017+/-0.002 mSv/MBq. A
      majority of primary pancreatic tumors and their metastases were visualized by
      (123)I-VEGF(165) scan. CONCLUSION: In vitro binding results confirmed specific
      binding of (123)I-VEGF(165) to pancreatic tumor cells and tissues. (123)I
      VEGF(165) shows favorable dosimetry and is a safe radiopharmaceutical that may be
      of potential value for the imaging of VEGF receptor status in vivo.

PMID- 15499295
TI  - Palliative treatment of painful disseminated bone metastases with 186Rhenium-HEDP
      in patients with lung cancer.
AB  - AIM: The aim of this study was to determine if patients with lung cancer and
      metastatic bone pain due to disseminated secondary bone disease, can benefit from
      the treatment with (186)Re-HEDP and to discuss the criteria useful for selecting
      those patients. METHODS: Twenty-four patients were included in this study and
      they received 1295 MBq (186)Re-HEDP. All patients underwent (99m)Tc-MDP bone scan
      before treatment from which the bone scan index (BSI) was determined (mean=18.7+/
      17.1%). Most patients underwent CT scan of the painful areas from which the
      osteolytic element of their bone lesions as well as possible infiltration of the
      soft tissues was determined. Patients with predominantly osteolytic metastases at
      the sites considered to be the origin of pain in the CT scan, were excluded. All
      patients were under analgesic therapy, 22/24 were taking opiates. Pain was
      estimated by the visual analogue scale (VAS) before the application of (186)Re
      HEDP and over the following 8 weeks. The possible myelotoxicity of (186)Re was
      assessed. RESULTS: The mean VAS score was 6.9+/-2.5 before the application and
      3.2+/-2.6 after therapy. Pain relief was obtained in 23/24 patients. Sixty-two
      percent of the patients exhibited clinically significant pain relief of at least
      3 VAS score. The dosage of opiates was decreased in 77% of the patients and could
      be discontinued in 4 of them. Myelotoxicity was observed in 1 patient. Ninety-one
      percent of our patients showed improvement in the parameters that assess the
      quality of life. CONCLUSION: The application of a standard dose of (186)Re-HEDP
      in patients with lung cancer and painful disseminated bone metastases has a
      satisfactory pain alleviating effect. The easy application and very low
      myelotoxicity are important factors in this group of patients. A better analgesic
      effect of the (186)Re-HEDP application can be expected if combined estimation of
      the (99m)Tc-MDP bone scan and the CT scan is used.

PMID- 15499296
TI  - Combined treatment of glioblastoma patients with locoregional pre-targeted 90Y
      biotin radioimmunotherapy and temozolomide.
AB  - AIM: In a previous phase I-II study, the safety profile and anti-tumor efficacy
      of pre-targeting locoregional radioimmunotherapy (LR-RIT), based on the ''3
      step'' method, was assessed in 24 high-grade glioma patients. The encouraging
      results in terms of low toxicity and objective response rate (25%) prompted us to
      continue our study. METHODS: An analysis of 73 patients with hystologically
      confirmed glioblastoma multiforme (GBM), treated with the ''3 step'' (90)Y-biotin
      based LR-RIT, is herein reported. All patients had a catheter implanted at 2(nd)
      surgery and underwent at least 2 cycles of LR-RIT (range 2-7) with 2 months
      interval. Thirty-five out of 73 patients were also treated with Temozolomide
      (TMZ). Two cycles of TMZ (200 mg/m(2)/day, for 5/28 days) were administered in
      between each course of LR-RIT. Overall survival (OS) and progression free
      survival (PFS) were retrospectively calculated. RESULTS: Stabilization of disease
      was achieved in 75% of patients, while 25% progressed. In the 38 patients treated
      with LR-RIT alone, median OS and PFS were respectively 17.5 months (95%CI=[17
      20]) and 5 months (95%CI=[4-8]), while in the 35 treated with the combined
      treatment (LR-RIT+TMZ) respective values were 25 months (95%CI=[23-30]) and 10
      months (95%CI=[9-18] (p<0.01). The addition of TMZ to LR-RIT did not increase
      neurological toxicity, and no major hematological toxicity was observed.
      CONCLUSION: These results confirm the safety and the efficacy of (90)Y LR-RIT in
      recurrent GBM patients; the addition of TMZ significantly improved the overall
      outcomes; a further controlled prospective, randomized study is fully justified.

PMID- 15499297
TI  - An in vitro study to compare 99mTc-stannous colloids and 99mTc-HMPAO for
      labelling human leukocytes.
AB  - AIM: Aim of the present study was to compare in vitro the labelling efficiency
      (LE) and cell viability (TBE) of autologous leukocytes labelled with (99m)Tc
      SnF(2) and (99m)Tc-HMPAO, and to evaluate the quantity and quality of
      spontaneously released (99m)Tc (SR) from labelled cells at several time points
      after labelling. METHODS: A total of 14 patients with different diseases and 18
      normal subjects were included in this study. A blood sample was collected from
      each patient; purified autologous leukocytes were divided into 2 samples and
      labelled with (99m)Tc-SnF(2) and (99m)Tc-HMPAO. LE was evaluated at the end of
      labelling and TBE and SR were evaluated at 10 min and 1 h, 2 h and 4 h after
      labelling. RESULTS: LE of (99m)Tc-SnF(2)-WBC was higher than (99m)Tc-HMPAO-WBC
      (61.2+/-18.7% and 43.3+/-11.3; p<0.0001) and we found an inverse correlation
      between blood glucose and labelling efficiency for both methods (p=0.02). Minimal
      differences were also observed between 2 methods after 10 min and 1 h, as far as
      the cell viability is concerned. The percentage of radioactivity spontaneously
      released from (99m)Tc-SnF(2)-WBC was significantly higher compared to (99m)Tc
      HMPAO-WBC at each time point. Radioactivity released from labelled cells was
      predominantly (99m)Tc-SnF(2) and (99m)Tc-HMPAO with few free (99m)Tc (<20%).
      CONCLUSION: Both radiopharmaceuticals are not toxic for WBC. Labelling with
      (99m)Tc-SnF(2) give a higher LE than with (99m)Tc-HMPAO; however, radiolabelled
      colloids are more released from labelled cells over a period of 4 h. While
      (99m)Tc-HMPAO is physiological excreted into gastrointestinal tract, (99m)Tc
      SnF(2) can be re-uptaken in vivo by reticulo-endothelial cells of liver and
      spleen. These findings suggest that (99m)Tc-SnF(2)-WBC might be better than
      (99m)Tc-HMPAO-WBC for studying inflammatory bowel diseases.

PMID- 15499298
TI  - Comparative evaluation of two methods to assay thyroglobulin serum concentrations
      in patients with differentiated thyroid carcinomas.
AB  - AIM: This study was aimed at the comparative assessment of the analytical and
      clinical performances of 2 tests for thyroglobulin (Tg) assays: the Dynotest Tg
      Plus immunoradiometric assay (IRMA), a new method that might be of interest for
      its claimed superior sensitivity compared to other methods, and the HTGK-2 IRMA,
      one of the test currently used in clinical routine. METHODS: The study was
      performed in serum samples from 157 patients with differentiated thyroid
      carcinoma (DTC). The clinical sensitivity of the test was evaluated in patients
      with and without thyroid stimulating hormone (TSH) suppression. RESULTS: The
      lowest detectable Tg concentration values and the within-assay coefficient of
      variation (CV) were 0.4 and 0.8 microg/L and 5% and 3% for the Dynotest Tg-Plus
      assay and the HTGK-2 assay, respectively; the between-assay CV was 6% for both
      assays. The clinical results of the Dynotest Tg-Plus and those of the HTGK-2 kit
      were similar in both DTC patient populations, either under or off the TSH
      suppressive treatment. In spite of the manufacturer's statement that the
      calibrators of both assays had been standardized against the same common
      reference (standard CRM 457 of the Community Bureau of References), the Dynotest
      Tg-Plus test underrated by a factor of 0.5 the Tg values measured by means of
      HTGK-2 IRMA. CONCLUSION: The sensitivity of the Dynotest Tg-Plus IRMA appears to
      be similar to that of the HTGK-2 assay.

PMID- 15499299
TI  - Damage to taste system and oral pain: burning mouth syndrome.
AB  - The burning mouth syndrome (BMS) is an oral pain disorder. Central or peripheral
      pain mechanisms may play a role in the oral burning of BMS. Various local,
      systemic and psychological factors have been found to be associated with BMS, but
      its etiology is not fully understood. This syndrome mostly affects middle-aged
      women and is frequently accompanied by taste complaints. This association of
      symptoms suggests an interaction between the mechanisms of nociception and
      gustation, 2 senses with strong hedonic components. There are connections between
      taste and oral pain in the central nervous system and it is possible that BMS and
      other oral pain phantoms result from damage to the taste system. This suggests
      that individuals who suffer from BMS are likely to be supertasters.

PMID- 15499300
TI  - Infection through sprays in medical devices for dentistry. A controllable
      epidemiological impact.
AB  - The risk of infections via dental sprays has been confirmed once again by the
      detection, inside dental unit waterlines, of bacterial and viral contaminations,
      both from water supplies and from the oral cavity of patients. Conventional means
      of prevention, flushing of the ducts before any dental treatment and anti
      retraction devices intended to avoid contamination originating from the patient,
      evaluated in laboratory and clinical conditions, have been shown to be
      ineffective in controlling the risk. Tests carried out in vitro, with circuit
      models, and with the dental unit in service, have confirmed the efficacy of a
      method to disinfect the waterlines with a disinfecting solution based on TAED and
      Peroxidant, which in aqueous solution develop peracetic ions (Autosteril method).
      Zero bacterial count, zero viral charge and a complete biofilm demolition were
      achieved both in lab conditions and in service units. After hygienic treatment,
      the same disinfection method, once installed on old units that had been in
      service for years and without any hygienic device, allowed us to restore and to
      maintain the microbiological quality of the irrigant also in dental units of old
      design, and significantly reduced biofilm formation inside the waterlines.
      Therefore, on the basis of scientific findings, a microbiologic monitoring
      protocol is proposed in order to verify the hygienic conditions of units which
      are in service.

PMID- 15499301
TI  - Descriptive and topographic anatomy of the accessory infraorbital foramen.
      Clinical implications in maxillary surgery.
AB  - AIM: Study of frequency and position of accessory infraorbital foramen in a large
      craniological sample. METHODS: A sample of 1 064 skulls from the craniological
      collection of the Department of Anatomy, Pharmacology and Forensic Medicine of
      the University of Turin (Italy) was investigated. RESULTS: Accessory infraorbital
      foramen was found in 4.7% of the skulls (5.4% in male and 4.26% in female skulls)
      with a higher frequency on the left side, both in male and in female skulls.
      CONCLUSION: These results increase our knowledge of the interindividual anatomic
      variability of the infraorbital region and can be of help for the maxillo-facial
      surgeon, especially in trunk block of the infraorbital nerve.

PMID- 15499302
TI  - Oral health comparison between the institutionalized and non institutionalized
      elderly.
AB  - AIM: The aim of the present epidemiological study is to gather information on the
      state of oral health in both hospitalized and non-hospitalized patients in Milan,
      in order to evaluate the prevalence of periodontal disease and to carry out a
      comparison between the 2 groups. METHODS: The study involved 364 patients (111
      males, 253 females) aged between 65 and 104, subdivided into 2 groups: 1) the
      1(st) group of 258 hospitalized patients; 2) the 2(nd) group consisted of 106 non
      hospitalized patients. In order to carry out the examinations 5 orthodontic
      mirrors, traditional orthodontic O.M.S. probes, and a source of white light were
      utilized. The epidemiological parameters utilized, according to O.M.S. criteria,
      were D.M.F.T. and C.P.I.T.N. RESULTS: The results obtained by the dental
      examinations were registered by means of the ''Scheda di Valutazione O.M.S''
      (O.M.S. Evaluation Report). Hospitalized patients D.M.F.T. 24,99, C.P.I.T.N.
      1,40; non-hospitalized patients D.M.F.T. 19,82, C.P.I.T.N. 1,78. 42.3% of
      patients proved to be edentulous (49.6% hospitalized patients; 28.3% non
      hospitalized patients). Of these, 45% wore dentures. CONCLUSION: The value of
      D.M.F.T. in elderly hospitalized patients was higher than in non-hospitalized
      patients; decay is thus prevalent in hospitalized patients. If we observe the
      values of C.P.I.T.N., a worrisome datum emerges: neither of the 2 groups are
      aware of correct oral hygiene techniques. Therefore, the clinical results derived
      from our study highlight the need to create a specific oral health program,
      directed at the elderly.

PMID- 15499303
TI  - The "piercing technique". A new procedure in impacted lower third molar surgery.
      Analysis of 802 consecutive extractions.
AB  - AIM: Our objective is to rationalize the odontotomic phase during the extraction
      of lower third molars. This study also evaluated the side effects and
      complications after the piercing technique utilized for surgery. METHODS: A total
      of 802 consecutive extractions of impacted lower third molars class B and C of
      Pell and Gregory were performed by the same surgeon in 506 patients with the
      ''Piercing Technique''. The incidence of complications and side effects was
      evaluated at 10, 21, 30, 60, 90 and 180 days. RESULTS: None of the patients had
      sensory impairment of the lingual nerve, mandibular fractures, displacement of
      the tooth in soft tissues or intra and post-operative haemorrhage. CONCLUSIONS:
      The data suggest that the ''Piercing Technique'' is very safe, minimally invasive
      and easy to apply in impacted lower third molar surgery. This surgical procedure
      represents the first operative stage of odontotomy and permits us to have a point
      of dental reference, that makes odontectomy as similar as possible to the ideal
      that we have thought. With this technique it is possible to inject anaesthetic
      into the dental pulp in cases of hypersensibility. It is also possible to have a
      point for insertion of angular elevators by making piercings in the tooth.

PMID- 15499304
TI  - Eagle's syndrome secondary surgical treatment. Report of a case.
AB  - Eagle's Syndrome is reported to be the symptomatic calcification of the
      stylohyoid complex. Calcification of the stylohyoid ligament is a relatively
      common finding in the general population, however only a small percentage of
      these people presents symptoms. According to the kind of symptoms described by
      the patients it is possible to recognise two syndromes: the classic one, which
      occurs after a tonsillectomy, and stylo-carotid artery syndrome, which is
      independent from a tonsillectomy. The only effective treatment in symptomatic
      cases is the surgical shortening of the styloid process. The case presented
      underlines the problems due to the persistence of the calcified caudal portion of
      the stylohyoid ligament after a first surgical removal. A second surgical
      treatment is suggested for a complete resection of the calcified ligament which
      was causing the symptomatology complained by the patient. This patient had
      previously undergone surgical shortening of the stylohyoid ligament after he was
      diagnosed as having Eagle's Syndrome, of the styloid-carotid artery type. After a
      stylohyoidectomy, he still suffered from dysphagia, neck pain and scratching
      sensation when swallowing. Further surgical treatment was necessary, with the aim
      of removing the caudal portion of the ligament, which was causing the patient's
      symptoms. An extra-oral approach was used and, after surgery, the patient was
      completely relieved of the symptoms. Conventional and three-dimensional CT were
      performed after surgery, they showed the complete absence of the left calcified
      stylohyoid ligament.

PMID- 15499305
TI  - Complications in implant surgery by Summer's technique: benign paroxysmal
      positional vertigo (BPPV).
AB  - The aim of this study is to show the correlation between implant surgery using an
      osteotomic technique and benign paroxysmal positional vertigo (BPPV). The case of
      a 55-year-old patient submitted to oral implant surgery in the 2.3 area is
      described. The ridge was thin in this particular location and therefore the
      maxillary expansion technique according to Summer was preferred. After removing
      the sutures, the patient suffered from vertigo and was in a confusional state.
      The patient was therefore placed in the Tredelenburg's position and a few minutes
      later he felt better. However, the symptomatology that seemed disappeared was
      present again the following day. A careful check-up showed the presence of BPPV,
      treated as described in this paper.

PMID- 15499306
TI  - Surveillance for waterborne-disease outbreaks associated with recreational water-
      United States, 2001-2002.
AB  - PROBLEM/CONDITION: Since 1971, CDC, the U.S. Environmental Protection Agency, and
      the Council of State and Territorial Epidemiologists have maintained a
      collaborative surveillance system for collecting and periodically reporting data
      related to occurrences and causes of waterborne-disease outbreaks (WBDOs) related
      to drinking water; tabulation of recreational water-associated outbreaks was
      added to the surveillance system in 1978. This surveillance system is the primary
      source of data concerning the scope and effects of waterborne disease outbreaks
      on persons in the United States. REPORTING PERIOD COVERED: This summary includes
      data on WBDOs associated with recreational water that occurred during January
      2001-December 2002 and on a previously unreported outbreak that occurred during
      1998. DESCRIPTION OF SYSTEM: Public health departments in the states,
      territories, localities, and the Freely Associated States are primarily
      responsible for detecting and investigating WBDOs and voluntarily reporting them
      to CDC on a standard form. The surveillance system includes data for outbreaks
      associated with both drinking water and recreational water; only outbreaks
      associated with recreational water are reported in this summary. RESULTS: During
      2001-2002, a total of 65 WBDOs associated with recreational water were reported
      by 23 states. These 65 outbreaks caused illness among an estimated 2,536 persons;
      61 persons were hospitalized, eight of whom died. This is the largest number of
      recreational water-associated outbreaks to occur since reporting began in 1978;
      the number of recreational water-associated outbreaks has increased significantly
      during this period (p<0.01). Of these 65 outbreaks, 30 (46.2%) involved
      gastroenteritis. The etiologic agent was identified in 23 (76.7%) of these 30
      outbreaks; 18 (60.0%) of the 30 were associated with swimming or wading pools.
      Eight (12.3%) of the 65 recreational water-associated disease outbreaks were
      attributed to single cases of primary amebic meningoencephalitis caused by
      Naegleria fowleri; all eight cases were fatal and were associated with swimming
      in a lake (n = seven; 87.5%) or river (n = one; 12.5%). Of the 65 outbreaks, 21
      (32.3%) involved dermatitis; 20 (95.2%) of these 21 outbreaks were associated
      with spas or pools. In addition, one outbreak of Pontiac fever associated with a
      spa was reported to CDC. Four (6.1%) of the 65 outbreaks involved acute
      respiratory illness associated with chemical exposure at pools. INTERPRETATION:
      The 30 outbreaks involving gastroenteritis comprised the largest proportion of
      recreational water-associated outbreaks during this reporting period. These
      outbreaks were associated most frequently with Cryptosporidium (50.0%) in treated
      water venues and with toxigenic Escherichia coli (25.0%) and norovirus (25.0%) in
      freshwater venues. The increase in the number of outbreaks since 1993 could
      reflect improved surveillance and reporting at the local and state level, a true
      increase in the number of WBDOs, or a combination of these factors. PUBLIC HEALTH
      ACTION: CDC uses surveillance data to identify the etiologic agents, types of
      aquatics venues, water-treatment systems, and deficiencies associated with
      outbreaks and to evaluate the adequacy of efforts (e.g., regulations and public
      awareness activities) for providing safe recreational water. Surveillance data
      are also used to establish public health prevention priorities, which might lead
      to improved water-quality regulations at the local, state, and federal levels.

PMID- 15499307
TI  - Surveillance for waterborne-disease outbreaks associated with drinking water-
      United States, 2001-2002.
AB  - PROBLEM/CONDITION: Since 1971, CDC, the U.S. Environmental Protection Agency, and
      the Council of State and Territorial Epidemiologists have maintained a
      collaborative surveillance system for collecting and periodically reporting data
      related to occurrences and causes of waterborne-disease outbreaks (WBDOs). This
      surveillance system is the primary source of data concerning the scope and
      effects of waterborne disease outbreaks on persons in the United States.
      REPORTING PERIOD COVERED: This summary includes data on WBDOs associated with
      drinking water that occurred during January 2001-December 2002 and on three
      previously unreported outbreaks that occurred during 2000. DESCRIPTION OF SYSTEM:
      Public health departments in the states, territories, localities, and the Freely
      Associated States are primarily responsible for detecting and investigating WBDOs
      and voluntarily reporting them to CDC on a standard form. The surveillance system
      includes data for outbreaks associated with both drinking water and recreational
      water; only outbreaks associated with drinking water are reported in this
      summary. RESULTS: During 2001-2002, a total of 31 WBDOs associated with drinking
      water were reported by 19 states. These 31 outbreaks caused illness among an
      estimated 1,020 persons and were linked to seven deaths. The microbe or chemical
      that caused the outbreak was identified for 24 (77.4%) of the 31 outbreaks. Of
      the 24 identified outbreaks, 19 (79.2%) were associated with pathogens, and five
      (20.8%) were associated with acute chemical poisonings. Five outbreaks were
      caused by norovirus, five by parasites, and three by non-Legionella bacteria. All
      seven outbreaks involving acute gastrointestinal illness of unknown etiology were
      suspected of having an infectious cause. For the first time, this MMWR
      Surveillance Summary includes drinking water-associated outbreaks of Legionnaires
      disease (LD); six outbreaks of LD occurred during 2001-2002. Of the 25 non
      Legionella associated outbreaks, 23 (92.0%) were reported in systems that used
      groundwater sources; nine (39.1%) of these 23 groundwater outbreaks were
      associated with private noncommunity wells that were not regulated by EPA.
      INTERPRETATION: The number of drinking water-associated outbreaks decreased from
      39 during 1999-2000 to 31 during 2001-2002. Two (8.0%) outbreaks associated with
      surface water occurred during 2001-2002; neither was associated with consumption
      of untreated water. The number of outbreaks associated with groundwater sources
      decreased from 28 during 1999-2000 to 23 during 2001-2002; however, the
      proportion of such outbreaks increased from 73.7% to 92.0%. The number of
      outbreaks associated with untreated groundwater decreased from 17 (44.7%) during
      1999-2000 to 10 (40.0%) during 2001-2002. Outbreaks associated with private,
      unregulated wells remained relatively stable, although more outbreaks involving
      private, treated wells were reported during 2001-2002. Because the only
      groundwater systems that are required to disinfect their water supplies are
      public systems under the influence of surface water, these findings support EPA's
      development of a groundwater rule that specifies when corrective action
      (including disinfection) is required. PUBLIC HEALTH ACTION: CDC and EPA use
      surveillance data 1) to identify the types of water systems, their deficiencies,
      and the etiologic agents associated with outbreaks and 2) to evaluate the
      adequacy of technologies for providing safe drinking water. Surveillance data are
      used also to establish research priorities, which can lead to improved water
      quality regulations. CDC and EPA recently completed epidemiologic studies that
      assess the level of waterborne illness attributable to municipal drinking water
      in nonoutbreak conditions. The decrease in outbreaks in surface water systems is
      attributable primarily to implementation of provisions of EPA rules enacted since
      the late 1980s. Rules under development by EPA are expected to protect the public
      further from microbial contaminants while addressing risk tradeoffs of
      disinfection byproducts in drinking water.

PMID- 15499309
TI  - Envisioning novel and meaningful collaborations: crucial leadership needed.

PMID- 15499310
TI  - Dispelling desperation in nursing education.

PMID- 15499311
TI  - The Nursing Research Center on HIV/AIDS Health Disparities.
AB  - This report describes the partnership between the schools of nursing at the
      University of California San Francisco and the University of Puerto Rico to
      address the need for nursing research on HIV/AIDS health disparities. The
      partnership led to the creation of the Nursing Research Center on HIV/AIDS Health
      Disparities with funding from the National Institutes of Health/National
      Institute of Nursing Research. We provide background information on the
      disproportionate impact of the HIV/AIDS epidemic on racial and ethnic minorities,
      describe the major predictors of health disparities in persons at risk for or
      diagnosed with HIV/AIDS using the Outcomes Model for Health Care Research, and
      outline the major components of the Nursing Research Center. The center's goal is
      to improve health outcomes for people living with and affected by HIV/AIDS by
      enhancing the knowledge base for HIV/AIDS care.

PMID- 15499312
TI  - Community-based research: barriers to recruitment of African Americans.
AB  - The elimination of health disparities for African Americans requires culturally
      relevant, empirical knowledge, which in turn requires including African Americans
      in research studies. However, power-difference barriers and conceptual barriers
      continue to inhibit the recruitment of African Americans. The purpose of this
      article is to define and discuss certain barriers to the recruitment of African
      Americans into research studies and to present culturally and contextually
      sensitive strategies to overcoming these barriers. Power-difference barriers
      reflect unequal authority and often generate mistrust. Conceptual barriers
      reflect researchers' need for better understanding about African Americans.
      Effective strategies include collaboration with the community through a community
      advisory board and conducting community-based participatory action research.
      Also, integrating alternative conceptual frameworks with mainstream frameworks
      may reduce researchers' ideological assumptions about African Americans. To
      promote optimal recruitment of African Americans, researchers must be aware of
      power-difference barriers and conceptual barriers and move toward active
      collaboration with African American communities.

PMID- 15499313
TI  - Development of a computer-based system for continence health promotion.
AB  - Computer-based systems (CBS) can provide information to help individuals analyze
      their health care needs and make decisions about management of health problems.
      This article discusses the development of a CBS that delivers an individualized
      educational intervention for continence health promotion. System development
      included cycles of prototype design, testing, analysis, and redesign. Knowledge
      acquisition, representation methods, and design decisions are discussed.
      Participants completed 4 rounds of usability testing and a pilot test, which
      resulted in enhancements to both the CBS and the expert system feature that
      produced individualized feedback. This iterative design process involved users
      throughout system development. User involvement resulted in a tutorial to explain
      navigation and other features of the CBS, graphics to enhance the written
      message, and clarification of continence-related content. The procedures resulted
      in an informative, usable product; they can be used to develop systems that
      provide information about symptom self-management for other health conditions.

PMID- 15499314
TI  - Identification of national trends in nursing education through the use of an
      online survey.
AB  - Increased access and familiarity with computer technology has enhanced research
      data collection and analysis processes. Use of the Internet in these processes is
      rapidly becoming an alternative to traditional paper and pencil methods and can
      be a useful tool in conducting nursing education research. The purpose of this
      article is to discuss the use of online survey methodologies to identify nursing
      education trends and disseminate information nationwide. Advantages,
      disadvantages and pitfalls of using e-mail in conducting a Web-based survey are
      presented. The authors describe relevant aspects of developing and implementing
      an online survey; relate their experience in using this survey method with regard
      to its strengths and limitations; and, comment regarding efficacy of electronic
      collection and analysis of research data. The authors' experience in conducting a
      previously published national study of the integration of holistic nursing
      practices and complementary and alternative modalities in curricula of
      baccalaureate and higher degree schools of nursing is used as an exemplar. The
      authors conclude that, regardless of the current status of technology and lack of
      computer support in some schools of nursing, an online national survey is a
      valuable tool in conducting research in nursing education and increasingly will
      be the method of choice for gathering survey data.

PMID- 15499315
TI  - The rhetoric of rupture: nursing as a practice with a history?
AB  - In this paper we argue that nursing is consistently presented as a practice
      without a history, constantly reinventing itself within new professional and
      technical realms. This rupture with and repudiation of a past deemed to be
      pejorative, coupled with a rebirth in a "preferred present," raises recurrent
      problems in the construction of nursing's contemporary professional identity and
      search for social legitimacy. Furthermore, constituting new nursing knowledge and
      practice as discontinuous with the past produces a sense of historical
      dislocation of that nursing knowledge and practice that, in turn, reproduces the
      need for relocation through reinvention. This phenomenon, which we term the
      "rhetoric of rupture," in our view, arises from nursing's frustrated attempts to
      gain social status and legitimacy. Paradoxically, this constant reinvention in
      fact hampers nurses' attempts to gain that status and legitimacy.

PMID- 15499316
TI  - "This food may contain ..." What nurses should know about genetically engineered
      foods.
AB  - Genetic engineering has been in existence since 1973. The process involves
      placing genetic DNA from one organism into another. Genetically engineered
      organisms (GEOs) are the name given to such new species of plants created through
      this process. Proponents of GEOs assert that foods we are now able to produce
      have greater nutritional value, longer shelf life, better appearance, taste and
      smell. There are positive benefits to genetic engineering of plants and animals.
      A growing concern for the health safety of genetically engineered plants and
      foods is developing among the cautious. The purpose of this article is to define
      genetic engineering, present benefits and risks, describe the impact on human
      health, and address implications for nursing.

PMID- 15499317
TI  - In memoriam: Ingeborg Grosser Mauksch, distinguished nurse leader.

PMID- 15499318
TI  - In memory: Ingeborg Grosser Mauksch.

PMID- 15499320
TI  - Remembering Jim Page: the man, the mentor, the guardian angel.

PMID- 15499321
TI  - In defense of traction splints.

PMID- 15499322
TI  - A call for research.

PMID- 15499323
TI  - Never wrestle with a pig.

PMID- 15499324
TI  - Downtown people.

PMID- 15499326
TI  - Treat the patient, not the rhythm.

PMID- 15499328
TI  - 2004 JEMS Salary & Workplace Survey: data to plan business strategies & guide
      career moves.

PMID- 15499329
TI  - Jane Doe v. EMS: viewing EMS under the legal microscope.

PMID- 15499330
TI  - How to document the unthinkable: 7 situations in which EMS records could become
      evidence in court.

PMID- 15499331
TI  - What's your duty?: when your legal obligation starts & where it ends.

PMID- 15499332
TI  - Sight-threatening eye injuries: prehospital management of ophthalmological
      emergencies.

PMID- 15499335
TI  - Electronic & data management issues: patient data security.

PMID- 15499337
TI  - What's your angle?

PMID- 15499338
TI  - "Bully boys" try to run EMS out of San Francisco Fire Department.

PMID- 15499347
TI  - Cooking habits provide a key to 5 a day success.

PMID- 15499348
TI  - Is blue dye safe as a method of detection for pulmonary aspiration?

PMID- 15499349
TI  - Cultural literacy in health care.

PMID- 15499350
TI  - Ryan White CARE Act reauthorization: Opportunities for patients and dietetics
      professionals.

PMID- 15499351
TI  - Culturally appropriate approaches are needed to reduce ethnic disparity in
      childhood obesity.

PMID- 15499352
TI  - A new emphasis on health care safety, quality, and cost containment: how will
      this affect dietetics practice?

PMID- 15499353
TI  - Design and development of food safety knowledge and attitude scales for consumer
      food safety education.
AB  - OBJECTIVE: The objective of this study was to design and develop food safety
      knowledge and attitude scales based on food-handling guidelines developed by a
      national panel of food safety experts. DESIGN: Knowledge (n=43) and attitude
      (n=49) questions were developed and pilot-tested with a variety of consumer
      groups. Final questions were selected based on item analysis and on validity and
      reliability statistical tests. SUBJECTS/SETTING: Knowledge questions were tested
      in Washington State with participants in low-income nutrition education programs
      (pretest/posttest n=58, test/retest n=19) and college students (pretest/posttest
      n=34). Attitude questions were tested in Ohio with nutrition education program
      participants (n=30) and college students (non-nutrition majors n=138, nutrition
      majors n=57). STATISTICAL ANALYSES PERFORMED: Item analysis, paired sample t
      tests, Pearson's correlation coefficients, and Cronbach's alpha were used.
      RESULTS: Reliability and validity tests of individual items and the question sets
      were used to reduce the scales to 18 knowledge questions and 10 attitude
      questions. The knowledge and attitude scales covered topics ranked as important
      by a national panel of experts and met most validity and reliability standards.
      The 18-item knowledge questionnaire had instructional sensitivity (mean score
      increase of more than three points after instruction), internal reliability
      (Cronbach's alpha >.75), and produced similar results in test-retest without
      intervention (coefficient of stability=.81). Knowledge of correct procedures for
      hand washing and avoiding cross-contamination was widespread before instruction.
      Knowledge was limited regarding avoiding food preparation while ill, cooking
      hamburgers, high-risk foods, and whether cooked rice and potatoes could be stored
      at room temperature. The 10-item attitude scale had an appropriate range of
      responses (item difficulty) and produced similar results in test-retest ( P
      </=.01). Internal consistency ranged from alpha=.63 to .89. Students anticipating
      a career where food safety is valued had higher attitude scale scores than
      participants of extension education programs. CONCLUSIONS: Uses for the knowledge
      questionnaire include assessment of subject matter knowledge before instruction
      and knowledge gain after instruction. The attitude scale assesses an outcome
      variable that may predict food safety behavior.

PMID- 15499354
TI  - Food safety practices and readiness to implement HACCP programs in assisted
      living facilities in Iowa.
AB  - OBJECTIVE: To evaluate current food-handling practices and employee food safety
      knowledge and attitudes and to provide baseline data for implementing the Hazard
      Analysis and Critical Control Point (HACCP) program in assisted-living
      foodservices for elderly persons. DESIGN: Food-handling practices were observed
      at each assisted-living facility using a structured observation form. A validated
      questionnaire was used to determine demographic information and employees'
      attitudes and knowledge about food safety. SUBJECTS/SETTING: A convenience sample
      of 40 assisted-living facilities in Iowa was recruited from a list obtained from
      the Iowa Department of Elder Affairs. STATISTICAL ANALYSES PERFORMED: Descriptive
      statistics were used to summarize data. One-way analysis of variance was used to
      assess differences in attitudes and food safety knowledge among the managers,
      cooks, and other foodservice employees. Multiple linear regression determined the
      relationship between manager and facility demographics and the food safety
      practice score. RESULTS: Proper food-handling practices were followed in many
      assisted-living facilities, but areas in need of improvement were identified.
      Some HACCP prerequisite programs were found to be inadequate, including a lack of
      written standard operating procedures, documentation of food safety practices,
      and training. Temperatures and chemical concentrations need to be checked
      routinely. Foodservice employees had a significant amount of food safety
      knowledge (14.6+/-3.0 out of 20 possible points), and employees with food safety
      certification scored higher than those with no certification (15.6+/-2.6 and
      13.9+/-3.1, respectively; P </=.001). CONCLUSIONS: Training programs, both basic
      food safety and the HACCP program, will support improvement of safe food-handling
      practices and implementation of prerequisite programs and the HACCP program.
      Developing prerequisite programs, including sanitation standard operating
      procedures, will aid assisted-living facilities in moving toward HACCP program
      implementation.

PMID- 15499355
TI  - Changes in food group consumption patterns from childhood to young adulthood: the
      Bogalusa Heart Study.
AB  - OBJECTIVE: The objective of this study was to assess changes in food group
      consumption patterns from childhood to young adulthood. DESIGN: Twenty-four-hour
      dietary recalls were collected on a longitudinal sample of young adults.
      SUBJECTS/SETTING: Dietary intake data were collected on 246 young adults (70%
      European American, 30% African American) aged 19 to 28 years who participated in
      a previous cross-sectional survey when they were 10-year-olds. STATISTICAL
      ANALYSES: Descriptive statistics and linear mixed models adjusting for study time
      (age), sex, and ethnicity. RESULTS: In childhood, consumption of fruits/fruit
      juice and mixed meats ( P </=.05), desserts, candy, and milk ( P </=.0001) were
      greater than in young adulthood. Young adulthood consumption was greater for
      sweetened beverages, poultry and seafood ( P </=.001), salty snacks ( P </=.05),
      and beef ( P </=.01) compared to childhood. Milk consumption decreased, but the
      decrease was greater among males ( P </=.0001). Sweetened beverage consumption
      increased, but the increase was greater for European Americans ( P </=.0001).
      Candy consumption decreased, but the decrease was greater for African Americans (
      P </=.05). CONCLUSIONS: Changes occur in food group consumption patterns from
      childhood to young adulthood. Overall, there was a decrease in diet quality
      during this age transition. Understanding eating habits of children early in life
      is important for planning effective intervention strategies.

PMID- 15499356
TI  - Food safety practices and HACCP implementation: perceptions of registered
      dietitians and dietary managers.
AB  - OBJECTIVE: Assess perceptions of consultant registered dietitians (RDs) and
      dietary managers about food safety practices and Hazard Analysis and Critical
      Control Point (HACCP) implementation in assisted-living and long-term care
      facilities for the elderly. DESIGN: A mail questionnaire was developed using a
      modified Delphi process. Respondents were asked to assess food safety concerns in
      facilities where employed, identify prerequisite programs, rate barriers to
      implementation of HACCP, and provide demographic information. SUBJECTS/SETTING:
      The survey was sent to a random sample from national membership in the American
      Dietetic Association's Consultant Dietitians in Health Care Facilities dietetic
      practice group (n=1,181) and to all dietary managers who listed assisted living
      as their employment location as part of membership in the national Dietary
      Managers Association (n=274). STATISTICAL ANALYSES PERFORMED: Descriptive
      statistics were calculated for each questionnaire item for all respondents.
      Factor analyses and t test comparisons of items and factors determined if
      significant differences existed between perceptions of RDs and dietary managers.
      RESULTS: Both RDs and dietary managers identified employee knowledge and
      experience and food practices as food safety concerns. More than 80% of both RDs
      and dietary managers agreed that the majority of listed HACCP prerequisites were
      necessary. Respondents identified the greatest barriers to implementation of
      HACCP as those related to time. CONCLUSIONS: Findings indicate a need to develop
      written policies for food safety, such as access to production areas. To minimize
      risk of foodborne illness to the elderly, barriers to implementation of HACCP
      should be addressed, including commitment of time and resources to develop
      systems, train employees, and retain employees.

PMID- 15499357
TI  - Implementing hazard analysis critical control points.

PMID- 15499358
TI  - Ethnic differences in the prevalence of overweight among young children in
      Hawaii.
AB  - OBJECTIVES: To compare the prevalence of overweight among young children of
      different ethnic backgrounds and describe the age pattern of overweight in early
      childhood. METHODS: Cross-sectional study of 21,911 children, 12 to 59 months
      old, participating in the Hawaii Special Supplemental Nutrition Program for
      Women, Infants, and Children in 1997-1998. They were grouped in eight ethnic
      categories. For 1-year-olds we defined overweight as weight-for-age at the 95th
      percentile or more and underweight as weight-for-age at less than the 10th
      percentile. For 2- to 4-year-olds overweight was defined as body mass index (BMI)
      at the 95th percentile or more, underweight as BMI less than 10th percentile,
      tall stature as height-for-age at the 95th percentile or more, and short stature
      as height-for-age at less than the 10th percentile. The National Center for
      Health Statistics 2000 growth charts were the reference values. The analysis
      included bivariate and multivariate methods. RESULTS: Large differences were
      found among ethnic groups. Among 1-year-olds, Samoans were the heaviest (17.5%
      overweight) and Filipinos the lightest (30.2% underweight). Among 2- to 4-year
      olds, Samoans were the heaviest (27.0% overweight) and the tallest (16.9% tall),
      whereas Asians were the lightest (12.2% underweight), and Filipinos the shortest
      (19.0% short). Hawaiians and Asians also had a high percentage of short children
      (13.6% and 12.2%, respectively). Prevalence of overweight in all 2- to 4-year
      olds was more than the expected 5%, especially for Samoans, Filipinos, Hawaiians,
      and Asians. At age 2 to 4 years, overweight was almost twice as prevalent as at
      age 1. Multivariate analysis showed that ethnicity (Samoan) had the strongest
      independent association with weight-for-age percentile, BMI, and overweight in
      the two age groups, followed by birth weight. CONCLUSIONS: This is the first
      study of overweight among children of Asian and Pacific Island backgrounds in
      Hawaii. It identified important characteristics of growth and will be helpful in
      the design of appropriate activities to prevent overweight.

PMID- 15499359
TI  - Food safety: emerging trends in foodborne illness surveillance and prevention.
AB  - Between 250 and 350 million Americans are estimated to suffer acute
      gastroenteritis annually, with 25% to 30% thought to be caused by foodborne
      illnesses. Most vulnerable to foodborne diseases are elderly people, pregnant
      women, immune-compromised people, and children. While bacterial causes such as
      Salmonella are widely recognized and monitored as foodborne infections, other
      important bacterial causes such as Clostridium perfringens , Bacillus cereus ,
      and Staphylococcus aureus are less well known. While the majority of cases of
      foodborne diseases are of unknown cause, bacteria and viruses are the most likely
      causative agents. Caliciviridae (Norwalk-like) virus cases are more difficult to
      identify, but represent the most common cause of known and probably unknown
      cases. Fresh produce has to be added to the traditional list of foods requiring
      careful selection and handling to prevent foodborne disease. To assess the
      disease burden in the United States, morbidity and mortality surveillance
      activities are done by several networks and systems with collaboration among
      federal agencies and health departments. Not all important causes are being
      equally monitored. Critical behaviors by food processors, food retailers,
      foodservice personnel, and consumers can reduce the risk of foodborne illness
      episodes. Dietetics professionals can more readily monitor new developments and
      update knowledge and practice through online resources.

PMID- 15499360
TI  - Self-identified knowledge and practices of family physicians in Appalachian Ohio
      regarding food acquisition of patients.
AB  - This study assessed the self-identified food security knowledge and practices of
      family physicians practicing in Appalachian Ohio, along with related factors,
      using a 17-item survey. Respondents (n=189, 42.2%) were primarily male (n=151,
      79.9%), white (n=172, 91%), US citizens (n=182, 96.8%), rural inhabitants (n=137,
      72.5%), and doctors of medicine (n=19, 63.3%). Only 29 (16.0%) of the family
      physicians strongly agreed (n=2, 1.1%) or agreed (n=27, 14.9%) that they were
      knowledgeable about food security. A food security practice score (n=189, 3.4+/
      2.4) was computed using a multi-item question (Cronbach's alpha=0.76). Food
      security knowledge was related to (Kendall's tau) age (0.137, P =.028), years as
      a physician (0.162, P =.004), and food security practice score (0.161, P =.007).
      Family physicians involved in improving community food security had greater food
      security practice scores (n=43, 4.9+/-2.9), compared with those who did not
      (n=138, 2.9+/-2.0) ( P <.001). Education of family physicians about food
      insecurity and considering food security in practice is warranted.

PMID- 15499361
TI  - Microbiological evaluation of foodservice contact surfaces in Iowa assisted
      living facilities.
AB  - A study of 40 assisted-living facilities in Iowa was conducted to assess the
      microbiological quality of food-contact surfaces (work tables/counters, cooking
      equipment such as mixing bowls, and cutting boards) and a surface that could
      cross-contaminate food (refrigerator or freezer handles) to determine the
      effectiveness of cleaning and sanitation. Standards were set for foodservice for
      aerobic plate count, Enterobacteriaceae, and Staphylococcus aureus . Two
      facilities met standards for all five surfaces for each of the three tests. Fewer
      facilities met the standard for aerobic plate count than for the other two tests,
      and nearly three fourths of the facilities failed to meet the aerobic plate count
      for cutting boards. Critically, cross-contamination from these surfaces could
      result in contamination of food; thus, attention needs to be given to training
      and supervision to ensure proper hand washing and appropriate cleaning and
      sanitation procedures to reduce or eliminate cross-contamination.

PMID- 15499362
TI  - Estimated phytochemical content of the dietary approaches to stop hypertension
      (DASH) diet is higher than in the Control Study Diet.
AB  - The Dietary Approaches to Stop Hypertension (DASH) diet substantially lowers
      blood pressure and reduces blood lipid levels. The DASH diet menus were designed
      to reach beneficial levels of fiber, potassium, magnesium, and calcium, and
      therefore contain more fruits, vegetables, and whole grains relative to the
      control menus, and consequently more phytochemicals. Using the US Department of
      Agriculture food composition databases, the polyphenol, carotenoid, and
      phytosterol contents of the diets used in the DASH study were estimated. When
      compared with the control diet, the DASH diet is higher in flavonols, flavanones,
      flavan-3-ols, beta-carotene, beta-cryptoxanthin, lycopene, lutein+zeaxanthin, and
      phytosterols. Flavone levels are similar, whereas isoflavones are present in a
      small amount in the DASH diet. The roles of these compounds in disease risk
      reduction are becoming recognized. It therefore is possible that the health
      benefits of the DASH diet are partially attributable to the phytochemicals and
      might extend beyond cardiovascular disease risk reduction.

PMID- 15499363
TI  - Harriet Holt Cloud, MS, RD, receives 2004 Copher Memorial award.

PMID- 15499374
TI  - CD95 apoptosis resistance in certain cells can be overcome by noncanonical
      activation of caspase-8.
AB  - CD95 apoptosis resistance of tumor cells is often acquired through mutations in
      the death domain (DD) of one of the CD95 alleles. Furthermore, Type I cancer
      cells are resistant to induction of apoptosis by soluble CD95 ligand (CD95L),
      which does not induce efficient formation of the death-inducing signaling complex
      (DISC). Here, we report that tumor cells expressing a CD95 allele that lacks a
      functional DD, splenocytes from heterozygous lpr(cg) mice, which express one
      mutated CD95 allele, and Type I tumor cells stimulated with soluble CD95L can all
      die through CD95 when protein synthesis or nuclear factor kappa B is inhibited.
      This noncanonical form of CD95-mediated apoptosis is dependent on the enzymatic
      activity of procaspase-8 but does not involve fully processed active caspase-8
      subunits. Our data suggest that it is possible to overcome the CD95 apoptosis
      resistance of many tumor cells that do not efficiently form a DISC through
      noncanonical activation of the caspase-8 proenzyme.

PMID- 15499375
TI  - Bax affects intracellular Ca2+ stores and induces Ca2+ wave propagation.
AB  - In the present study, we evaluated proapoptotic protein Bax on mitochondria and
      Ca2+ homeostasis in primary cultured astrocytes. We found that recombinant Bax
      (rBax, 10 and 100 ng/ml) induces a loss in mitochondrial membrane potential
      (Delta Psi m). This effect might be related to the inhibition of respiratory
      rates and a partial release of cytochrome c, which may change mitochondrial
      morphology. The loss of Delta Psi m and a selective permeabilization of
      mitochondrial membranes contribute to the release of Ca2+ from the mitochondria.
      This was inhibited by cyclosporin A (5 microM) and Ruthenium Red (1 microg/ml),
      indicating the involvement of mitochondrial Ca2+ transport mechanisms. Bax
      induced mitochondrial Ca2+ release evokes Ca2+ waves and wave propagation between
      cells. Our results show that Bax induces mitochondrial alteration that affects
      Ca2+ homeostasis and signaling. These changes show that Ca2+ signals might be
      correlated with the proapoptotic activities of Bax.

PMID- 15499376
TI  - Ca2+ depletion induces nuclear clusterin, a novel effector of apoptosis in
      immortalized human prostate cells.

PMID- 15499377
TI  - Positron emission tomography (PET) imaging of tumor-localized Salmonella
      expressing HSV1-TK.
AB  - In order to noninvasively detect Salmonella delivery vectors within tumors, we
      used a genetically modified Salmonella, VNP20009, that expresses the herpes
      simplex thymidine kinase (HSV1-tk) reporter gene. VNP20009-TK were able to
      selectively localize within murine tumor models and to effectively sequester a
      radiolabeled nucleoside analogue, 2'-fluoro-1-beta-D-arabino-furanosyl-5-iodo
      uracil (FIAU). A quantitative relationship between the level of radioactivity
      accumulated and the number of bacteria in tumor and different tissues was
      demonstrated. The in vivo accumulation of [14C]FIAU measured in tissue sample
      homogenates and sections were related to Salmonella number and to
      immunohistochemical bacterial staining, respectively. Quantitative
      autoradiography (QAR) revealed the relative intensity of [14C]FIAU accumulation
      in a tumor cross-section, demonstrating that the peripheral region of the tumor
      was significantly less active than internal regions. [124I]FIAU positron emission
      tomography (PET) and subsequent tissue radioactivity and bacterial concentration
      measurements were compared. A log-log relationship was found, and the PET images
      could identify multiple tumor sites. The ability to noninvasively detect
      Salmonella vectors by PET imaging has the potential to be conducted in a clinical
      setting, and could aid in development of these vectors by demonstrating the
      efficiency and duration of targeting as well as indicating the locations of
      tumors.

PMID- 15499378
TI  - Silencing of the IGF1R gene enhances sensitivity to DNA-damaging agents in both
      PTEN wild-type and mutant human prostate cancer.
AB  - The type 1 insulin-like growth factor receptor (IGF1R) is overexpressed in
      prostate cancer, and mediates proliferation, motility, and survival. Many
      prostate cancers harbor inactivating PTEN mutations, enhancing Akt
      phosphorylation. This activates the principal antiapoptotic pathway downstream of
      the IGF1R, calling into question the value of IGF1R targeting in this tumor. The
      aim of the current study was to assess the effect of IGF1R gene silencing in
      prostate cancer cells that lack functional PTEN protein. In human DU145, LNCaP
      and PC3 prostate cancer cells, transfection with IGF1R small interfering RNA
      induced significant enhancement of apoptosis and inhibition of survival, not only
      in PTEN wild-type DU145 but also in PTEN mutant LNCaP and PC3. This was
      attributed to attenuation of IGF signaling via Akt, ERKs and p38. In both DU145
      and PC3, IGF1R knockdown led to enhancement of sensitivity to mitoxantrone,
      etoposide, nitrogen mustard and ionizing radiation. There was no sensitization to
      paclitaxel or 5-fluorouracil, which do not damage DNA, suggesting that
      chemosensitization results from impairment of the DNA damage response, in
      addition to removal of apoptosis protection. These results support the concept of
      IGF1R targeting in prostate cancer, and indicate that PTEN loss does not render
      tumor cells refractory to this strategy.

PMID- 15499379
TI  - Suicide gene therapy: conversion of ethanol to acetaldehyde mediated by human
      beta 2 alcohol dehydrogenase.
AB  - Acetaldehyde (AcH) produced in the physiological metabolism of ethanol can be
      potentially toxic and immunomodulating. The antitumour activity of a suicide gene
      system using adenovirus delivered alcohol dehydrogenase (ADH) to convert ethanol
      to acetaldehyde inside cancer cells has been investigated in vitro and in vivo.
      In vitro experiments confirmed the toxicity of acetaldehyde to a number of tumour
      cell lines. Daudi lymphoma cells grown in normal media increased by Day 4 to 650%
      of their starting number, while those exposed to 250 microM, 500 microM and 1 mM
      acetaldehyde reached 138, 30 and 5% respectively. Adenocarcinoma cells appeared
      to be less sensitive with CMT-64 cells and HeLa cells numbering 105 and 53% of
      their starting number by Day 4 with 1 mM acetaldehyde. After transduction with an
      adenovirus containing the human ADH beta 2 cDNA, CMT-64 cells exposed to 20 mM
      ethanol had a reduction in number to 74% by Day 2 and to 36% by Day 4. In a
      preclinical model with Ad-ADH CMT-64 cells, mice exposed to daily pulses of
      ethanol for 5 days formed tumours only 30% on Day 6 and 42% on Day 13 of the
      volume of those in mice exposed to water. The ability of this easily administered
      suicide gene system to produce significant effects on cell proliferation in vivo
      suggests that further optimized development is warranted.

PMID- 15499380
TI  - A novel fusion suicide gene yeast CDglyTK plays a role in radio-gene therapy of
      nasopharyngeal carcinoma.
AB  - To investigate a novel suicide gene for nasopharyngeal carcinoma (NPC) therapy,
      the yCDglyTK gene was constructed by fusing yeast cytosine deaminase (CD) and
      herpes simplex type 1 thymidine kinase. The expression of the yCDglyTK gene was
      detected by RT-PCR and Western blotting, and its bioactivity was demonstrated by
      an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. An
      animal study was carried out in which BALB/C nude mice bearing yCDglyTK gene
      modified tumors were treated with prodrugs and radiation. Our results revealed
      that the yCDglyTK gene could be expressed in CNE-2 cells in vitro. In MTT
      analysis, at the transfection rate of 10%, 66% cells were killed. The synergistic
      effect of CD and TK showed 91% of yCDglyTK-transfected cells were killed with the
      treatment of 5-fluorocytosine (5-FC) alone, 60% killed with ganciclovir (GCV)
      alone, and 75% killed with 5-FC and GCV together. In vivo, the tumor volume in
      all of the four prodrugs and/or radiation-treated groups were significantly
      different from that in the PBS-controlled group (P<.01); also
      yCDglyTK+prodrug+radiation group was different from the other three groups
      (P<.05). Our findings suggested there was a synergistic antitumor effect when
      combining suicide gene therapy and radiation, and yCDglyTK has potent antitumor
      efficacy and may be a candidate suicide gene for cancer therapy.

PMID- 15499381
TI  - Role of Serine 286 in cosubstrate binding and catalysis of a flavonol O
      methyltransferase.
AB  - O-Methyltransferases catalyze the transfer of the methyl groups of S-adenosyl-L
      methionine to specific hydroxyl groups of several classes of flavonoid compounds.
      Of the several cDNA clones isolated from a Chrysosplenium americanum library,
      FOMT3' encodes the 3'/5'-O-methylation of partially methylated flavonols. The
      recombinant protein of another clone, FOMTx which differs from FOMT3' by a single
      amino acid residue (Ser286Arg) exhibits no enzymatic activity towards any of the
      flavonoid substrates tested. Replacement of Ser 286 in FOMT3' with either Ala,
      Leu, Lys or Thr, almost abolished O-methyltransferase activity. In contrast with
      FOMT3', no photoaffinity labeling could be achieved using [(14)CH(3)]AdoMet with
      the mutant recombinant proteins indicating that Ser 286 is also required for
      cosubstrate binding. These results are corroborated by isothermal titration
      microcalorimetry measurements. Circular dichroism spectra ruled out any
      significant conformational differences in the secondary structures of both FOMT3'
      and Ser286Arg. Modeling FOMT3' on the structure of chalcone methyltransferase
      indicates that serine 286 is greater than 10 A from any of the residues of the
      active site or the AdoMet binding site of FOMT3'. At the same time, residues 282
      to 290 are conserved in most of the Chrysosplenium americanum OMTs. These
      residues form a large part of the subunit interface, and at least five of these
      residues are within 4 A of the opposing subunit. It would appear, therefore, that
      mutations in Ser286 exert their influence by altering the contacts between the
      subunits and that these contacts are necessary for maintaining the integrety of
      the AdoMet binding site and active site of this group of enzymes.

PMID- 15499382
TI  - Identification of the linker histone H1 as a protein kinase Cepsilon-binding
      protein in vascular smooth muscle.
AB  - A variety of anchoring proteins target specific protein kinase C (PKC) isoenzymes
      to particular subcellular locations or multimeric signaling complexes, thereby
      achieving a high degree of substrate specificity by localizing the kinase in
      proximity to specific substrates. PKCepsilon is widely expressed in smooth muscle
      tissues, but little is known about its targeting and substrate specificity. We
      have used a Far-Western (overlay) approach to identify PKCepsilon-binding
      proteins in vascular smooth muscle of the rat aorta. Proteins of approximately 32
      and 34 kDa in the Triton-insoluble fraction were found to bind PKCepsilon in a
      phospholipid/diacylglycerol-dependent manner. Although of similar molecular
      weight to RACK-1, a known PKCepsilon-binding protein, these proteins were
      separated from RACK-1 by SDS-PAGE and differential NaCl extraction and were not
      recognized by an antibody to RACK-1. The PKCepsilon-binding proteins were further
      purified from the Triton-insoluble fraction and identified by de novo sequencing
      of selected tryptic peptides by tandem mass spectrometry as variants of the
      linker histone H1. Their identity was confirmed by Western blotting with anti
      histone H1 and the demonstration that purified histone H1 binds PKCepsilon in the
      presence of phospholipid and diacylglycerol but absence of Ca(2+). The
      interaction of PKCepsilon with histone H1 was specific since no interaction was
      observed with histones H2A, H2S or H3S. Bound PKCepsilon phosphorylated histone
      H1 in a phospholipid/diacylglycerol-dependent but Ca(2+)-independent manner.
      Ca(2+)-dependent PKC was also shown to interact with histone H1 but not other
      histones. These results suggest that histone H1 is both an anchoring protein and
      a substrate for activated PKCepsilon and other PKC isoenzymes and likely serves
      to localize activated PKCs that translocate to the nucleus in the vicinity of
      specific nuclear substrates including histone H1 itself. Since PKC isoenzymes
      have been implicated in regulation of gene expression, stable interaction with
      histone H1 may be an important step in this process.

PMID- 15499383
TI  - Dynamin- and clathrin-dependent endocytic pathway in unicellular eukaryote
      Paramecium.
AB  - The first evidence of dynamin presence and its colocalization with clathrin in
      the compartment involved in Paramecium receptor-mediated endocytosis is
      presented. We identified dynamin by cloning, Western blotting, and
      immunodetection in confocal and electron microscopy. The partial genes, which we
      have designated ParDyn1 and ParDyn2, are 1091 bp long, 90% identical to one
      another and encode the N-terminal and middle domains of Paramecium dynamin
      isoform 1 and isoform 2. The deduced amino acid sequences contain all three
      guanosine 5'-triphosphate (GTP)-binding motifs and show 67% homology to mammalian
      dynamins. Antibodies generated against the cloned GTPase domain revealed dynamin
      association with endosomes containing transferrin, the marker of receptor
      mediated endocytosis. In Western blotting a strong immunoreactive polypeptide of
      approximately 116 kDa, which seems to be phosphorylated, was accompanied by a
      faint one of approximately 90 kDa in cytosolic fraction (S2). Dynamin level was
      correlated with internalization of transferrin and it was significantly decreased
      upon inhibition of this process. Immunogold labeling in electron microscopy
      revealed colocalization of dynamin and clathrin in coated pits and endocytic
      vesicles. Moreover, the polypeptide cross-reaction with 2 different antibodies
      against mammalian clathrin was identified by immunoblotting. These results
      indicate that dynamin- and clathrin-dependent pathway exists in this evolutionary
      ancient cell.

PMID- 15499384
TI  - The effect of TNF-alpha on glycosylation pathways in bovine synoviocytes.
AB  - Synoviocytes are fibroblastic cells that line joint cavities. These cells
      synthesize numerous cell-surface and extracellular-matrix glycoproteins that are
      required for maintenance of the joint. Joint inflammation, such as occurs in
      arthritis, has been shown to have major effects on synoviocyte proliferation and
      on the biosynthesis of glycoproteins. The structures of the carbohydrate moieties
      of glycoproteins, however, and the enzymes involved in their synthesis have not
      yet been described for synoviocytes. Therefore, to characterize the cell-surface
      glycoconjugates, synoviocytes were isolated from bovine ankles, and the cells
      were grown in primary cultures. Lectin-binding assays were used to identify
      exposed N- and O-glycan carbohydrate determinants on synoviocytes, and specific
      enzyme assays were used to identify some of the glycosyltransferases involved in
      the synthesis of the glycan chains. A number of the enzymes that synthesize N-
      and O-linked oligosaccharides were found to be active in cell-free extracts of
      synoviocytes, including those that synthesize core-1-based O-glycans and the more
      complex bi-antennary N-glycans. To understand the molecular events underlying the
      inflammatory response in the synovium of arthritis patients, we examined the
      effect of the inflammatory cytokine tumour necrosis factor alpha (TNF-alpha) on
      synoviocytes and on glycosylation profiles. TNF-alpha treatment, which induces
      apoptosis in synoviocytes, was accompanied by changes in lectin-binding patterns,
      indicating alterations in the expression of cell-surface oligosaccharides.
      Concurrently, changes in specific enzyme activities were observed in treated
      cells. Two enzymes potentially important to the inflammatory process, core 2
      beta6-GlcNAc-transferase and beta4-Gal-transferase, increased after TNF-alpha
      treatment. This is the first study of glycoprotein biosynthesis in synoviocytes,
      and it shows that synoviocytes have a characteristic glycosylation phenotype that
      is altered in the presence of inflammatory cytokines.

PMID- 15499385
TI  - Complex expression pattern of the Barth syndrome gene product tafazzin in human
      cell lines and murine tissues.
AB  - Tafazzins, a group of proteins that are defective in patients with Barth
      syndrome, are produced by alternate splicing of the gene G4.5 or TAZ. RT-PCR and
      transcription-coupled in vitro translation analysis were undertaken to determine
      the expression of alternatively spliced TAZ mRNA in mouse tissues and human cell
      lines. Only two tafazzin transcripts, both lacking exon 5, were expressed in
      murine tissues, whereas four tafazzin transcripts, all lacking exon 5, were
      observed in human umbilical vein vascular endothelial cells and U937 human
      monoblasts indicating a species-specific difference in the expression of TAZ
      mRNAs in mouse and humans. Only TAZ lacking exon 5 was expressed in murine heart.
      Differentiation of U937 human monoblasts into macrophages did not alter
      expression of the tafazzin transcripts indicating that TAZ expression is
      independent of monocyte differentiation. Cloning and in vitro expression of both
      murine and human tafazzin cDNA revealed two prominent protein bands that
      corresponded to the expected sizes of alternative translation. A novel fifth
      motif, identified as critical for the glycerolphosphate acyltransferase family,
      was observed in human tafazzin. The presence of a mutation in this region in
      Barth syndrome patients indicates that this motif is essential for tafazzin
      function.

PMID- 15499386
TI  - BJ-HCC-20, a potential novel cancer-testis antigen.
AB  - In an effort to identify novel Cancer-Testis genes, we analyzed the sequence in
      the q26-28 region of human X chromosome by several on-line tools. The candidate
      sequences were then confirmed by experiments. We have obtained a novel Cancer
      Testis gene, BJ-HCC-20. In vivo, it was found to have two isoforms. In samples of
      liver, colon, gastric and lung cancer tested, the expression frequency of BJ-HCC
      20 is 25%, 17%, 21% and 15%, respectively. Full-length cDNAs of both BJ-HCC-20
      isoforms were isolated and their gene structures and promoter regions were
      characterized. BJ-HCC-20 might have implications in theoretical and practical
      tumor biology.

PMID- 15499387
TI  - Induction of G1 cell cycle arrest in human umbilical vein endothelial cells by
      flavone's inhibition of the extracellular signal regulated kinase cascade.
AB  - Dietary flavonoids have demonstrated anti-carcinogenic activity in several animal
      models, but their mechanisms of action have not yet been clearly established.
      Here, we show that flavone, a parent compound of flavonoids, inhibits the
      proliferation, migration, and capillary tube formation of human umbilical vein
      endothelial cells (HUVECs). Flow cytometric analysis showed that flavone arrests
      the cell cycle progression at G(1) phase in HUVECs. We observed the down
      regulation of the hyperphosphorylated form of retinoblastoma gene product and
      cyclin-dependent kinases 2 and 4 in flavone-treated cells, but it had no affect
      on the expression of p53 and cyclin-dependent kinase inhibitors p21(CIP/Waf1) and
      p27(Kip). Flavone almost completely inhibited the activation of extracellular
      signal regulated kinase 1. The present results suggest that the flavone moiety of
      flavonoids is required for anti-proliferative activity of flavonoids and that
      anti-carcinogenic action of flavonoids in vivo was mediated, at least in part, by
      inhibiting angiogenesis.

PMID- 15499389
TI  - Glomerular mesangial cell adhesion to fibrinogen is mediated by alphavbeta3
      integrin.
AB  - The biological behavior of glomerular mesangial cells is thought to play a
      critical role in human and experimental forms of mesangioproliferative
      glomerulonephritis. In these diseases, mesangial cells proliferate and produce
      increased amounts of extracellular matrix proteins, which can lead to
      glomerulosclerosis and end-stage renal disease. Mesangial cells interact with
      extracellular matrix proteins through integrin-mediated cell adhesion. Fibrinogen
      as a plasma-derived protein is known to be deposited in the mesangium of kidneys
      affected by mesangioproliferative glomerulonephritis. The adhesive interactions
      between fibrinogen and mesangial cells, however, have not been reported. Results
      in this work show that mesangial cells adhere to immobilized fibrinogen in an
      integrin-dependent fashion. This process was inhibited by the alphavbeta3
      selective peptide cyclo-RGDFV and the monoclonal anti-beta3 integrin chain
      antibody F11. Ca(2+) ions are a known strong inhibitor of the fibrinogen
      alphavbeta3 interaction, and mesangial cell adhesion did not occur when Ca(2+)
      was the only divalent cation present. Therefore, mesangial cell adhesion to
      fibrinogen is mediated by alphavbeta3 integrin, and divalent cations have a
      fundamental role in regulating this process.

PMID- 15499388
TI  - Suppression of clonogenicity by mammalian Dnmt1 mediated by the PCNA-binding
      domain.
AB  - Overexpression of the major DNA methyltransferase Dnmt1 is cytotoxic and has been
      hypothesized to result in aberrant hypermethylation of genes required for cell
      survival. Indeed, overexpression of mouse or human Dnmt1 in murine and human cell
      lines decreased clonogenicity. By frame-shift and deletion constructs, this
      effect of mouse Dnmt1 was localized at the N-terminal 124 amino acid domain,
      which mediates interaction with proliferating cell nuclear antigen (PCNA).
      Mutation of the PCNA-binding site restored normal cloning efficiencies.
      Overexpression of Dnmt3A or Dnmt3B, which do not interact with PCNA, yielded
      weaker effects on clonogenicity. Following introduction of the toxic domain, no
      significant effects on apoptosis, replication, or overall DNA methylation were
      observed for up to 3 d. Suppression of clonogenicity by Dnmt1 was also observed
      in cell lines lacking wild-type p53, p21(CIP1), or p16(INK4A). Suppression of
      clonogenicity by Dnmt1 overexpression may act as a fail-safe mechanism against
      carcinogenicity of sustained Dnmt1 overexpression.

PMID- 15499391
TI  - The prevalence and evolution of sex in microorganisms.
AB  - The origin of sex and how sex is maintained are among the biggest puzzles in
      biology. Most investigations into this problem have focused on complex eukaryotes
      like animals and plants. This mini-review summarizes recent progress in our
      understanding of the evolution of sex, highlighting results from studies of
      experimental and natural populations of microorganisms. Increasing evidence
      indicates that sexual reproduction in natural populations of viruses, bacteria,
      and eukaryotic microbes is much more prevalent than previously thought. In
      addition, investigations using experimental microbial populations are providing
      important parameters relevant to our understanding of the origin and maintenance
      of sex. It is argued that microbes are excellent model organisms to explore the
      mechanisms responsible for the evolution of sex.

PMID- 15499392
TI  - Restriction enzyme digestion chromosome banding in Crassostrea and Ostrea
      species: comparative karyological analysis within Ostreidae.
AB  - Reliable banding techniques are a major necessity for genetic research in
      oysters. In this study, we carried out the cytogenetic characterization of four
      oyster species (family Ostreidae) using restriction endonuclease treatments.
      Chromosomes were treated with three different restriction enzymes, stained with
      Giemsa, and examined for banding patterns. The following species were studied:
      Crassostrea gigas (2n = 20; total number of bands with ApaI, 74; HaeIII, 61;
      PstI, 76), Crassostrea angulata (2n = 20; ApaI, 62; HaeIII, 61; PstI, 55)
      (subfamily Crassostreinae), Ostrea edulis (2n = 20; ApaI, 82; HaeIII, 59; PstI,
      66), and Ostrea conchaphila (2n = 20; ApaI, 68; HaeIII, 62; PstI, 69) (subfamily
      Ostreinae). Treatment of samples with ApaI, HaeIII, and PstI produced specific
      banding patterns, which demonstrates the potential of these enzymes for
      chromosome banding in oysters. This is of special interest, since it has been
      recently shown in mammalian chromosomes that restriction enzyme banding is
      compatible with fluorescence in situ hybridization. This study therefore provides
      a fundamental step in genome mapping of oysters, since chromosome banding with
      restriction enzymes facilitates physical gene mapping in these important
      aquaculture species. The analysis of the banded karyotypes revealed a greater
      similarity within the genera of Crassostrea and Ostrea than between them.

PMID- 15499393
TI  - Microsatellite markers provide evidence for sexual reproduction of Mycosphaerella
      graminicola in Saskatchewan.
AB  - This study examined the genetic structure of a Saskatchewan population of
      Mycosphaerella graminicola, cause of the foliar disease Septoria tritici blotch
      of wheat. Such knowledge is valuable for understanding the evolutionary potential
      of this pathogen and for developing control strategies based on host resistance.
      Nine pairs of single-locus microsatellite primers were used to analyze the
      genomic DNA of 90 isolates of M. graminicola that were collected using a
      hierarchical sampling procedure from different locations, leaves, and lesions
      within a wheat field near Saskatoon. Allelic series at eight different loci were
      detected. The number of alleles per locus ranged from one to five with an average
      of three alleles per locus. Genetic diversity values ranged from 0.04 to 0.67.
      Partitioning the total genetic variability into within- and among-location
      components revealed that 88% of the genetic variability occurred within
      locations, i.e., within areas of 1 m(2), but relatively little variability
      occurred among locations. Low variability among locations and a high degree of
      variability within locations would result if the primary source of inoculum was
      airborne ascospores, which would be dispersed uniformly within the field. This
      finding was confirmed by gametic disequilibrium analysis and suggests that the
      sexual reproduction of M. graminicola occurs in Saskatchewan.

PMID- 15499394
TI  - Survey in the sugarcane expressed sequence tag database (SUCEST) for simple
      sequence repeats.
AB  - Sugarcane microsatellites or simple sequence repeats (SSR) were developed in an
      economical and practical way by mining EST databases. A survey in the SUCEST
      (sugarcane EST) database revealed a total of 2005 clusters out of 43,141
      containing SSRs. Of these, 8.2% were dinucleotide, 30.5% were trinucleotide, and
      61.3% were tetranucleotide repeats. Except for dinucleotides, the CG-rich motif
      types were the most common. Differences in abundance of trinucleotide motif types
      were observed between EST-SSRs and those isolated from sugarcane genomic
      libraries. Among the different cDNA libraries used for EST sequencing, SSRs were
      more frequent in the ones derived from leaf roll (LR). Twenty-three out of 30
      tested SSRs produced scorable polymorphisms in 18 sugarcane commercial clones.
      These EST-SSRs showed a moderate level of polymorphism with some SSRs producing
      unique fingerprints. The number of alleles observed among the 18 clones evaluated
      varied from 2 to 15, with an average of 6.04 alleles/locus. The polymorphism
      information content (PIC) values ranged from 0.28 to 0.90 with a mean of 0.66.
      The EST-SSRs screened over both parents (SP 80-180; SP 80-4966) and 6 F1
      individuals produced 52 segregating markers that could potentially be used for
      sugarcane mapping. The EST-SSRs were found in clusters that had significant
      homology to proteins involved in important metabolic pathways such as sugar
      biosynthesis, proving that EST-SSRs are a valuable tool for the construction of a
      functional sugarcane map.

PMID- 15499395
TI  - Development and mapping of EST-derived simple sequence repeat markers for
      hexaploid wheat.
AB  - Expressed sequence tags (ESTs) are a valuable source of molecular markers. To
      enhance the resolution of an existing linkage map and to identify putative
      functional polymorphic gene loci in hexaploid wheat (Triticum aestivum L.), over
      260,000 ESTs from 5 different grass species were analyzed and 5418 SSR-containing
      sequences were identified. Using sequence similarity analysis, 156 cross-species
      superclusters and 138 singletons were used to develop primer pairs, which were
      then tested on the genomic DNA of barley (Hordeum vulgare), maize (Zea mays),
      rice (Oryza sativa), and wheat. Three-hundred sixty-eight primer pairs produced
      PCR amplicons from at least one species and 227 primer pairs amplified DNA from
      two or more species. EST-SSR sequences containing dinucleotide motifs were
      significantly more polymorphic (74%) than those containing trinucleotides (56%),
      and polymorphism was similar for markers in both coding and 5' untranslated (UTR)
      regions. Out of 112 EST-SSR markers, 90 identified 149 loci that were integrated
      into a reference wheat genetic map. These loci were distributed on 19 of the 21
      wheat chromosomes and were clustered in the distal chromosomal regions. Multiple
      loci were detected by 39% of the primer pairs. Of the 90 mapped ESTs, putative
      functions for 22 were identified using BLASTX queries. In addition, 80 EST-SSR
      markers (104 loci) were located to chromosomes using nullisomic-tetrasomic lines.
      The enhanced map from this study provides a basis for comparative mapping using
      orthologous and PCR-based markers and for identification of expressed genes
      possibly affecting important traits in wheat.

PMID- 15499396
TI  - Features of a 103-kb gene-rich region in soybean include an inverted perfect
      repeat cluster of CHS genes comprising the I locus.
AB  - The I locus in soybean (Glycine max) corresponds to a region of chalcone synthase
      (CHS) gene duplications affecting seed pigmentation. We sequenced and annotated
      BAC clone 104J7, which harbors a dominant i(i) allele from Glycine max 'Williams
      82', to gain insight into the genetic structure of this multigenic region in
      addition to examining its flanking regions. The 103-kb BAC encompasses a gene
      rich region with 11 putatively expressed genes. In addition to six copies of CHS,
      these genes include: a geranylgeranyltransferase type II beta subunit
      (E.C.2.5.1.60), a beta-galactosidase, a putative spermine and (or) spermidine
      synthase (E.C.2.5.1.16), and an unknown expressed gene. Strikingly, sequencing
      data revealed that the 10.91-kb CHS1, CHS3, CHS4 cluster is present as a perfect
      inverted repeat separated by 5.87 kb. Contiguous arrangement of CHS paralogs
      could lead to folding into multiple secondary structures, hypothesized to induce
      deletions that have previously been shown to effect CHS expression. BAC104J7 also
      contains several gene fragments representing a cation/hydrogen exchanger, a 40S
      ribosomal protein, a CBL-interacting protein kinase, and the amino terminus of a
      subtilisin. Chimeric ESTs were identified that may represent read-through
      transcription from a flanking truncated gene into a CHS cluster, generating
      aberrant CHS RNA molecules that could play a role in CHS gene silencing.

PMID- 15499397
TI  - Map positions of third chromosomal female sterile and lethal mutations of
      Drosophila melanogaster.
AB  - Chromosomal mutations induced by ethyl methanesulfonate (EMS) treatment can cause
      female sterility or maternal-effect lethality in Drosophila. EMS is particularly
      useful to researchers because it creates mutations independent of position
      effects. However, because researchers have little control over the chromosomal
      site of mutation, post-mutagenic genetic mapping is required to determine the
      cytological location of the mutation. To make a valuable set of mutants more
      useful to the research community, we have mapped the uncharacterized part of the
      female-sterile - maternal-effect lethal Tubingen collection. We mapped 49 female
      sterile - maternal-effect lethal alleles and 72 lethal alleles to individual
      deficiency intervals on the third chromosome. In addition, we analyzed the
      phenotype of ovaries resulting from female sterile mutations. The observed
      phenotypes range from tumorous ovaries and early blocks in oogenesis, to later
      blocks, slow growth, blocks in stage 10, to apparently full development of the
      ovary. The mapping and phenotypic characterization of these 121 mutations provide
      the necessary information for the researcher to consider a specific mutant as a
      candidate for their gene of interest.

PMID- 15499398
TI  - Polyploidization-induced genome variation in triticale.
AB  - Polyploidization-induced genome variation in triticale (x Triticosecale Wittmack)
      was investigated using both AFLP and RFLP analyses. The AFLP analyses were
      implemented with both EcoRI-MseI (E-M) and PstI-MseI (P-M) primer combinations,
      which, because of their relative differences in sensitivity to cytosine
      methylation, primarily amplify repetitive and low-copy sequences, respectively.
      The results showed that the genomic sequences in triticale involved a great
      degree of variation including both repetitive and low-copy sequences. The
      frequency of losing parental bands was much higher than the frequency of gaining
      novel bands, suggesting that sequence elimination might be a major force causing
      genome variation in triticale. In all cases, variation in E-M primer-amplified
      parental bands was more frequent in triticale than that using P-M primers,
      suggesting that repetitive sequences were more involved in variation than low
      copy sequences. The data also showed that the wheat (Triticum spp.) genomes were
      relatively highly conserved in triticales, especially in octoploid triticales,
      whereas the rye (Secale cereale L.) genome consistently demonstrated a very high
      level of genomic sequence variation (68%-72%) regardless of the triticale ploidy
      levels or primers used. In addition, when a parental AFLP band was present in
      both wheat and rye, the tendency of the AFLP band to be present in triticale was
      much higher than when it was present in only one of the progenitors. Furthermore,
      the cDNA-probed RFLP analyses showed that over 97% of the wheat coding sequences
      were maintained in triticale, whereas only about 61.6% of the rye coding
      sequences were maintained, suggesting that the rye genome variation in triticale
      also involved a high degree of rye coding sequence changes. The data also
      suggested that concerted evolution might occur in the genomic sequences of
      triticale. In addition, the observed genome variation in wheat-rye addition lines
      was similar to that in triticale, suggesting that wheat-rye addition lines can be
      used to thoroughly study the genome evolution of polyploid triticale.

PMID- 15499399
TI  - Ability of scalloped deletion constructs to rescue sd mutant wing phenotypes in
      Drosophila melanogaster.
AB  - Scalloped (SD) and Vestigial (VG) proteins physically interact to form a selector
      complex that activates genes involved in wing development in Drosophila
      melanogaster. SD belongs to a conserved family of transcription factors
      containing the TEA/ATTS DNA-binding motif. VG is also a nuclear protein providing
      the activator function for the SD VG complex. The TEA DNA-binding domain and the
      VG interacting domain (VID) of SD have been previously identified and described.
      However, they, and possibly other functional domains of SD, have not been
      thoroughly characterized in vivo. Herein, transgenic constructs encoding various
      truncations of SD were used to assess their respective ability to rescue the
      mutant wing phenotype of two viable sd recessive mutations (sd(ETX4) and
      sd(58d)). The transgenic strains produced were also tested for the ability to
      induce further sd expression, an ability possessed by full length SD. The
      functional dissection of SD confirms that specific regions are necessary for wing
      development and provides further information as to how the SD VG complex
      functions to promote wing fate. Previous experiments have shown that expression
      of full length SD can cause a dominant negative wing phenotype. We show that
      expression of constructs that delete the SD DNA-binding domain can also cause a
      dominant negative phenotype in a background with either of the two tester sd
      strains. In contrast, SD constructs that delete the VID have no effect on the
      wing phenotype in either tester background. Finally, a significant portion of SD
      at the N-terminal end appears to be dispensable with respect to normal wing
      development, as this construct behaves the same as full length SD in our assays.

PMID- 15499400
TI  - Alterations in subtelomeric tandem repeats during early stages of allopolyploidy
      in wheat.
AB  - The genomic content of the subtelomeric repeated sequences Spelt1 and Spelt52 was
      studied by dot, Southern, and in situ hybridization in 11 newly synthesized
      amphiploids of Aegilops and Triticum, and data were compared with the parental
      plants. Spelt1 had reduced copy numbers in the first generation of three
      synthetic amphiploids, but two others did not change; Spelt52 was amplified in
      nine amphiploids and did not change in two. In the second allopolyploid
      generation, Spelt1 copy number did not change, whereas there was amplification of
      Spelt52 in some allopolyploids and decreases in others. Neither allopolyploidy
      level nor the direction of the cross affected the patterns of change in the newly
      synthesized amphiploids. Changes did not result from intergenomic recombination
      because similar alterations were noticed in allopolyploids with and without Ph1,
      a gene that suppresses homoeologous pairing. No differences in Spelt1 and Spelt52
      tandem organization were found by Southern hybridization. The significance of
      these data are discussed in relation to the establishment of newly formed
      allopolyploids.

PMID- 15499401
TI  - Mining EST databases to resolve evolutionary events in major crop species.
AB  - Using plant EST collections, we obtained 1392 potential gene duplicates across 8
      plant species: Zea mays, Oryza sativa, Sorghum bicolor, Hordeum vulgare, Solanum
      tuberosum, Lycopersicon esculentum, Medicago truncatula, and Glycine max. We
      estimated the synonymous and nonsynonymous distances between each gene pair and
      identified two to three mixtures of normal distributions corresponding to one to
      three rounds of genome duplication in each species. Within the Poaceae, we found
      a conserved duplication event among all four species that occurred approximately
      50-60 million years ago (Mya); an event that probably occurred before the major
      radiation of the grasses. In the Solanaceae, we found evidence for a conserved
      duplication event approximately 50-52 Mya. A duplication in soybean occurred
      approximately 44 Mya and a duplication in Medicago about 58 Mya. Comparing
      synonymous and nonsynonymous distances allowed us to determine that most
      duplicate gene pairs are under purifying, negative selection. We calculated
      Pearson's correlation coefficients to provide us with a measure of how gene
      expression patterns have changed between duplicate pairs, and compared this
      across evolutionary distances. This analysis showed that some duplicates seemed
      to retain expression patterns between pairs, whereas others showed uncorrelated
      expression.

PMID- 15499402
TI  - Structural and transcriptional features of Bombus terrestris satellite DNA and
      their potential involvement in the differentiation process.
AB  - A unique satellite DNA family was characterized in the genome of the bumble bee,
      Bombus terrestris. Sequence analysis revealed that it contains two wide
      palindromes of about 160 and 190 bp, respectively, that span 75% of the repeated
      unit. One feature of this satellite DNA is that it accounts for different amounts
      of genomic DNA in males and females. The DNA curvature and bendability were
      determined by migration on PAGE and by computer analysis. It has been correlated
      with the presence of dA/dT stretches repeated in phase with the helix turn and
      with the presence of the deformable dinucleotide CA-TG embedded in some of these
      A-T-rich regions. Transcription of the satellite DNA was also analyzed by
      Northern blot hybridization and RT-PCR. Multimeric transcripts spanning several
      satellite DNA units were found in RNA samples from males, workers, and queens.
      These transcripts resulted from a specific transcription occurring on one DNA
      strand in the embryos or on both DNA strands in imagoes. The involvement of DNA
      curvature in the organization of the satellite DNA and the function of the
      satellite transcripts is discussed.

PMID- 15499403
TI  - Microsatellite variability among wild and cultivated hops (Humulus lupulus L.).
AB  - Hop (Humulus lupulus L.) is a dioecious perennial plant native to the northern
      hemisphere cultivated for its use in the brewing industry. To investigate the
      genetic diversity present in wild hop accessions in comparison with cultivated
      hops, microsatellite marker variation was assessed at four loci in 124 accessions
      of wild (from Europe, Asia and from North America) and cultivated (varieties and
      breeding lines) hops. A total of 63 alleles were identified, with an average of
      15.7 alleles per locus and an average PIC of 0.64 over four loci. The average
      number of alleles per locus in groups of accessions ranged from 5.75 to 8.30,
      with the highest number detected in groups of wild hops either of European (EU)
      or North American (NA) origin. Accessions from NA revealed the highest number of
      unique alleles indicating the high diversity present in this gene pool. Cluster
      analysis based on the D(D) or D(sw) distance matrix divided accessions into 10
      different clusters, which reflect the relationship among geographically diverse
      wild accessions and hop cultivars. The highest genetic differences were found
      between NA wild accessions, forming one distant cluster, and all the other
      accessions. The differentiation between European wild and cultivated accessions
      was revealed by PCoA based on the D(D) distance matrix and by AMOVA results.
      Cultivated hops differ significantly from wild ones, although most of the
      variability was found within groups. The molecular variances within groups of
      cultivated and wild hops were homogeneous, suggesting that a similar level of
      molecular variability is found in both groups of accessions. The analysis of
      allele polymorphism and of allele sequences showed that hop germplasm can be
      differentiated to NA and EU geographic types according to the differences of
      allele sizes at three loci or by the specific microsatellite repeat type at one
      locus. The analysis also indicates the different evolutionary dynamics and
      complex mutations of microsatellite sequences within loci that can be followed in
      the two biogeographically separated germplasms.

PMID- 15499404
TI  - A genome-wide analysis of courting and mating responses in Drosophila
      melanogaster females.
AB  - In Drosophila melanogaster, seminal fluid proteins influence several components
      of female physiology and behavior, including re-mating rates, ovulation and
      oviposition, and sperm use. It is well-known that female flies are not simply
      passive vessels and that female-mediated interactions with male products are
      important to female (and thus male) reproductive success. While the population
      genetics, molecular evolution and physiological effects of seminal fluid proteins
      have been examined, the genetics and evolution of the female side of these post
      mating interactions is unexplored in spite of work showing that female genotype
      and female-by-male genotype interactions are important determinants of sperm
      competition outcomes. Here we use microarrays to identify candidate genes
      involved in the female side of post-mating sexual interactions. We report the
      results of a whole-genome oligonucleotide chip experiment that reveals 23 genes
      differentially expressed between virgin females exposed and unexposed to courting
      males, and 38 genes differentially expressed between virgin and recently mated
      females. Immune related genes are overrepresented among the mating-influenced
      candidates. We use quantitative reverse-transcriptase PCR to independently assess
      gene expression changes for roughly half of the mating-affected candidate genes.

PMID- 15499405
TI  - PCR identification of durum wheat BAC clones containing genes coding for
      carotenoid biosynthesis enzymes and their chromosome localization.
AB  - Carotenoids are essential components in all plants. Their accumulation in wheat
      seed determines the endosperm colour, which is an important quality trait in
      wheat. In this study, we report the isolation of BAC clones containing genes
      coding for three different enzymes of the carotenoid biosynthesis pathway:
      phytoene synthase (PSY), phytoene desaturase (PDS), and zeta-carotene desaturase
      (ZDS). Primers were designed on the basis of wheat ESTs similar to the sequences
      of these three genes in other species, and used to screen a BAC library from
      Triticum turgidum var. durum (2n = 28, genomes AABB). Eight, six, and nine 384
      well plates containing at least one positive clone were found for PSY, PDS, and
      ZDS, respectively. BACs selected for each of these genes were then divided in two
      groups corresponding to the A and B genomes of tetraploid wheat, based on
      differences in the length of the PCR amplification products, conformation
      sensitive gel electrophoresis (CSGE), or cleavage amplification polymorphisms.
      Positive clones were then assigned to chromosomes using a set of D genome
      substitution lines in T. turgidum var. durum 'Langdon'. PSY clones were localized
      on chromosomes 5A and 5B, PDS on chromosomes 4A and 4B, and ZDS on chromosomes 2A
      and 2B. The strategies used for the PCR screening of large BAC libraries and for
      the differentiation of BAC clones from different genomes in a polyploid species
      are discussed.

PMID- 15499406
TI  - High-resolution mapping of the S and Z loci of Phalaris coerulescens.
AB  - Self incompatibility (SI) in Phalaris coerulescens is gametophytically determined
      by two unlinked multi allelic loci (S and Z). Neither the S nor Z genes have yet
      been cloned. As part of a map-based cloning strategy, high-resolution maps of the
      S and Z regions were generated from distorted segregating populations using RFLP
      probes from wheat, barley, oat, and Phalaris. The S locus was delimited to 0.26
      cM with two boundary markers (Xwg811 and Xpsr168) and cosegregated with Xbm2 and
      Xbcd762. Xbcd266 was the closest marker linked to Z (0.9 cM). A high level of
      colinearity in the S and Z regions was found in both self-incompatible and 
      compatible species. The S locus was localized to the subcentromere region of
      chromosome 1 and the Z locus to the long arm end of chromosome 2. Several rice
      BAC clones orthologous to the S and Z locus regions were identified. This opens
      the possibility of using the rice genome sequence data to generate more closely
      linked markers and identify SI candidate genes. These results add further support
      to the conservation of gene order in the S and Z regions of the grass genomes.

PMID- 15499407
TI  - Identification of Fetuin-B as a member of a cystatin-like gene family on mouse
      chromosome 16 with tumor suppressor activity.
AB  - Studies of mouse models for multistage carcinogenesis have led to the
      identification of a susceptibility locus for skin tumor development (Skts9) in
      the proximal region of mouse chromosome 16. This chromosome region shows a loss
      of heterozygosity or an allelic imbalance in mouse skin and pancreatic islet
      carcinoma, and has been associated with angiogenesis. The microsatellite marker
      D16Mit2, which has the strongest linkage to skin tumor susceptibility, was used
      to screen a bacterial artificial chromosome (BAC) library, leading to the
      identification of the histidine-rich glycoprotein (Hrg) and Fetuin-B as the most
      tightly linked genes. These genes are members of a cystatin-like superfamily that
      includes the neighboring genes Kng and Ahsg/Fetuin. Overexpression of Fetuin-B in
      skin squamous carcinoma cells led to suppression of tumor growth in nude mice.
      The neighboring genes Kng and Ahsg also have potential roles in angiogenesis and
      (or) tumor development, and several genes in this locus may be candidates for the
      Skts9 gene.

PMID- 15499408
TI  - GISHGenomic in situ hybridization reveals cryptic genetic differences between
      maize and its putative wild progenitor Zea mays subsp. parviglumis.
AB  - The aim of this paper is to test with genomic in situ hybridization the genomic
      affinities between maize and its putative progenitor Zea mays subsp. parviglumis.
      Blocking procedures were applied for the purpose of improving discrimination
      among chromosome regions. Unlabeled genomic DNA from Z. mays subsp. parviglumis
      as a blocking agent and labeled genomic DNA from maize were hybridized on maize
      chromosomes. On the other hand, mitotic metaphases from Z. mays subsp.
      parviglumis were blocked with unlabeled genomic DNA of maize and hybridized with
      labeled genomic DNA from Z. mays subsp. parviglumis. Both experiments showed that
      either maize or Z. mays subsp. parviglumis chromosomes have their own unique
      sequences. This means an unexpected degree of divergence if Z. mays subsp.
      parviglumis is the only progenitor of maize, a result that is discussed in
      relation to our previous genomic in situ hybridization observations and to the
      different scenarios proposed about the origin of maize.

PMID- 15499409
TI  - Genomic in situ hybridization in plants with small genomes is feasible and
      elucidates the chromosomal parentage in interspecific Arabidopsis hybrids.
AB  - Genomic in situ hybridization (GISH) is a useful tool to analyse natural
      polyploids, hybrid plants, and their backcross progenies as to their origin,
      genomic composition, and intergenomic rearrangements. However, in angiosperms
      with very small genomes (<0.6 pg/1 C), often only heterochromatic regions were
      found to be labeled. We have modified the GISH technique to label entire mitotic
      and meiotic chromosomes of Arabidopsis thaliana (2n = 10) and closely related
      species with very small genomes by using high concentrations of DNA (7.5-15
      microg per probe per slide) or 5 microg of probe and long hybridization times
      (>60 h). According to our GISH data, Cardaminopsis carpatica (2n = 16) is most
      likely the diploid ancestor of the autotetraploid Arabidopsis arenosa (2n = 32).
      Furthermore, within the allotetraploid species Arabidopsis suecica (2n = 26), it
      was possible to elucidate the origin of chromosomes contributed by the parental
      species A. thaliana and A. arenosa for a specimen with 2n = 26 or a deviating
      chromosome number.

PMID- 15499410
TI  - A major suppressor of cell death, slm1, modifies the expression of the maize (Zea
      mays L.) lesion mimic mutation les23.
AB  - Disease lesion mimics provide an excellent biological system to study the genetic
      basis of cell death in plants. Many lesion mimics show variation in phenotype
      expression in different genetic backgrounds. Our goal was to identify
      quantitative trait loci (QTL) modifying lesion mimic expression thereby
      identifying genetic modifiers of cell death. A recessive lesion mimic, les23, in
      a severe-expressing line was crossed to the maize inbred line Mo20W, a lesion
      suppressing line, and an F(2) population was developed for QTL analysis. In
      addition to locating les23 to the short arm of chromosome 2, this analysis
      detected significant loci for modification of lesion expression. One highly
      significant locus was found on the long arm of chromosome 2. The Mo20W allele at
      this QTL significantly delayed initiation of the lesion phenotype and decreased
      the final lesion severity. Other QTL with lesser effect affected severity of
      lesion expression without affecting lesion initiation date. Our results
      demonstrate that dramatic change in lesion phenotype can be controlled by a
      single major QTL. The presumed function of this QTL in normal plants is to
      regulate some aspect of the cell death pathway underlying the les23 phenotype.

PMID- 15499411
TI  - Genome-wide analysis of Kluyveromyces lactis in wild-type and rag2 mutant
      strains.
AB  - The use of heterologous DNA arrays from Saccharomyces cerevisiae has been tested
      and revealed as a suitable tool to compare the transcriptomes of S. cerevisiae
      and Kluyveromyces lactis, two yeasts with notable differences in their
      respirofermentative metabolism. The arrays have also been applied to study the
      changes in the K. lactis transcriptome owing to mutation in the RAG2 gene coding
      for the glycolytic enzyme phosphoglucose isomerase. Comparison of the rag2 mutant
      growing in 2% glucose versus 2% fructose has been used as a model to elucidate
      the importance of transcriptional regulation of metabolic routes, which may be
      used to reoxidize the NADPH produced in the pentose phosphate pathway. At this
      transcriptional level, routes related to the oxidative stress response become an
      interesting alternative for NADPH use.

PMID- 15499412
TI  - Simultaneous painting of three genomes in hexaploid wheat by BAC-FISH.
AB  - Fluorescence in situ hybridization (FISH) is widely used in the physical mapping
      of genes and chromosome landmarks in plants and animals. Bacterial artificial
      chromosomes (BACs) contain large inserts, making them amenable for FISH mapping.
      In our BAC-FISH experiments, we selected 56 restriction fragment length
      polymorphism (RFLP)-locus-specific BAC clones from the libraries of Triticum
      monococcum and Aegilops tauschii, which are the A- and D-genome donors of wheat
      (Triticum aestivum, 2n = 6x = 42), respectively. The BAC clone 676D4 from the T.
      monococcum library contains a dispersed repeat that preferentially hybridizes to
      A-genome chromosomes, and two BAC clones, 9I10 and 9M13, from the Ae. tauschii
      library contain a dispersed repeat that preferentially hybridizes to the D-genome
      chromosomes. These repeats are useful in simultaneously discriminating the three
      different genomes in hexaploid wheat, and in identifying intergenomic
      translocations in wheat or between wheat and alien chromosomes. Sequencing
      results show that both of these repeats are transposable elements, indicating the
      importance of transposable elements, especially retrotransposons, in the genome
      evolution of wheat.

PMID- 15499413
TI  - Markers associated with stalk number and suckering in sugarcane colocate with
      tillering and rhizomatousness QTLs in sorghum.
AB  - Two important factors influencing sugar yield, the primary focus of sugarcane
      plant breeding programs, are stalk number and suckering. Molecular markers linked
      to both of these traits are sought to assist in the identification of high sugar
      yield, high stalk number, low-suckering sugarcane clones. In this preliminary
      mapping study, 108 progeny from a biparental cross involving two elite Australian
      sugarcane clones were evaluated at two sites for two years for both stalk number
      and suckering. A total of 258 DNA markers, including both restriction fragment
      length polymorphisms (RFLPs) and radio-labelled amplified fragments (RAFs), were
      scored and evaluated using single-factor analysis. Sixteen (7 RFLPs and 9 RAFs)
      and 14 (6 RFLPs and 8 RAFs) markers were identified that were significantly
      associated (P < 0.01) with stalk number and suckering, respectively, across both
      years and sites. The seven and six RFLP markers associated with stalk number and
      suckering, respectively, were generated by eight different RFLP probes, of which
      seven had been mapped in sorghum and (or) sugarcane. Of significant interest was
      the observation that all seven RFLP probes could be shown to be located within or
      near QTLs associated with tillering and rhizomatousness in sorghum. This
      observation highlights the usefulness of comparative mapping between sorghum and
      sugarcane and suggests that the identification of useful markers for stalk number
      and suckering in sugarcane would be facilitated by focussing on sorghum QTLs
      associated with related traits.

PMID- 15499414
TI  - Extracting DNA from submerged pine wood.
AB  - A DNA extraction protocol for submerged pine logs was developed with the
      following properties: (i) high molecular weight DNA, (ii) PCR amplification of
      chloroplast and nuclear sequences, and (iii) high sequence homology to voucher
      pine specimens. The DNA extraction protocol was modified from a
      cetyltrimehtylammonium bromide (CTAB) protocol by adding stringent
      electrophoretic purification, proteinase K, RNAse, polyvinyl pyrrolidone (PVP),
      and Gene Releaser. Chloroplast rbcL (ribulose-1,5-bisphosphate carboxylase) could
      be amplified. Nuclear ribosomal sequences had >95% homology to Pinus taeda and
      Pinus palustris. Microsatellite polymorphism for PtTX2082 matched 2 of 14 known
      P. taeda alleles. Our results show DNA analysis for submerged conifer wood is
      feasible.

PMID- 15499416
TI  - [Hepatitis C: revisited treatment].

PMID- 15499417
TI  - [The sustained response rates for chronic hepatitis C patients undergoing therapy
      with the several interferons and ribavarins supplied by Brazilians Health
      Ministry is comparable to those reported in the literature].
AB  - BACKGROUND: The sustained response rates of chronic hepatitis C therapy to
      interferons alpha 2A and 2B associated to ribavirin are described as
      approximately 40%. Nevertheless, studies on the sustained response rates in a
      setting of frequent changes of type of interferon as well as of supplies of
      interferons and ribavirin are lacking. AIMS: To evaluate the prevalence of
      sustained response and to determine the predictors of response to chronic
      hepatitis C therapy, in a cohort of outpatients at Curitiba, PR, south Brazil, in
      a setting of heterogeneous therapy regarding type and supply of the medications.
      POPULATION AND METHODS: A cohort of 87 chronic hepatitis C patients submitted to
      therapy with interferon alpha 2 and ribavirin were followed from August 1999 to
      August 2002. The prevalence of sustained response and the influence of gender,
      age, genotype and severity of liver fibrosis in the response were evaluated.
      RESULTS: A sustained response prevalence of 32.1% was found, positively
      associated to genotypes 2 and 3. CONCLUSIONS: Despite the frequent changes on
      product type and/or procedence, the sustained response prevalence rate found in
      this study was similar to that described in the literature.

PMID- 15499418
TI  - [Sexual and reproductive function in female liver transplant recipients].
AB  - BACKGROUND: Abnormalities in sexual and reproductive functions are common in
      women with end-stage liver disease and may be reversible after liver
      transplantation. AIM: Evaluate sexual and reproductive function in female
      recipients of liver transplantation at the Federal University of Parana,
      Curitiba, PR, Brazil. PATIENTS AND METHODS: Between September 1991 and December
      2001 94 women underwent liver transplantation at "Hospital de Clinicas" of the
      Federal University of Parana. Twenty-eight female recipients (mean age 44.17 +/-
      13.60 years old) fulfilled the following inclusion criteria: age > or = 16 years
      at liver transplant, post-transplant survival > or = 6 months, be alive and in
      regular follow-up at our Institution during the period of the study, and agreed
      to participate of the study. Medical records were reviewed and all subjects were
      answered by a questionnaire covering the following issues: timing and pattern of
      menstruation before and after transplant, sexual activity and contraceptive
      practices before and after transplant, pregnancy after transplant, frequency of
      cervical cytology and occurrence of gynecological malignant neoplasia after
      transplant, and aspects of sexuality domain after liver transplantation. RESULTS:
      The median post-transplant follow-up was 36.5 months (range, 6 to 110 months) and
      the main indication for liver transplantation was hepatitis C (25%). All patients
      had normal liver function tests. Excluding six patients who underwent
      hysterectomy or were in postmenopausal period, 13 of 22 women (59.1%) reported
      amenorrhea in the year before transplantation. After liver transplantation, 19 of
      22 patients (86.4%) promptly recovered menstrual function, after a median period
      of 1 month (range, 1 to 7 months). Normalization of menstrual function occurred
      in all women with age 45 or younger. About 71.4% of 28 women were sexually active
      after transplantation and 70% indicated satisfaction with their relationship.
      Four successful pregnancies (one gemelar) occurred in three patients and five
      healthy live-born infants have been delivered, all full term. Most of the
      patients had cervical cytology at least annually in the post-transplant period.
      One case of endometrial carcinoma was diagnosed in a 64 year old woman, three
      years after transplantation and was successfully treated by panhysterectomy.
      CONCLUSIONS: Most of female liver transplant recipients of child-bearing age
      recover menstrual function a few months after transplantation and successful
      pregnancy may occur. As libido and fertility return promptly after liver
      transplantation, patients should be counseled on safe contraception practices.
      Most of liver transplant recipients are sexually active and feel satisfied about
      their relationship. There is a good compliance of patients regarding screening
      for cervical neoplasm.

PMID- 15499419
TI  - [The influence of oral and pharyngeal phases on the swallowing dynamic].
AB  - BACKGROUND: The pharyngeal phase of swallowing has received more attention than
      oral phase although they are presumably interdependent. AIMS: 1. to evaluate,
      through the videofluoroscopic method, the oral phase of swallowing in order to
      observe the characteristics organization of the liquid bolus in healthy
      volunteers and the variations of this organization in exams of patient with
      dysphagia; 2. to establish the functional interrelation between both organization
      and ejection stages; 3. to verify the presence (or absence) of interference of
      the oral phase over the pharyngeal phase. CASUISTIC AND METHOD: Videofluoroscopic
      assessment has been performed in patients with stroke (15), patients with
      Parkinson disease (15) and in health volunteers (14). All of the studied
      individuals were submitted to the swallowing videofluoroscopic evaluation
      following protocol described by Junqueira and Costa. We privileged the incidence
      in right profile with middle of liquid contrast (solution of barium sulfate).
      RESULTS: According to the intra-oral organization of the contrasted bolus, we
      could classify the oral organization as: 1. closed, 2. open, that can be
      subdivided in open "anterior restricted" and "open expanded", 3. prolonged, and
      4. unstable. The ejection can be defined as: 1. appropriate, 2. lentify, and 3.
      in two times. The correlation among the oral dynamics acted by the organization
      and pharyngeal phases can be noticed as: 1. appropriate, 2. adapted, and 3.
      altered. The organization and ejection types as well as the observed correlations
      are shown with statistics significance. CONCLUSIONS: The closed organization type
      was the one characterized as normal. The "open expanded", "prolonged" and
      "unstable" organization type can be associated with alteration in the swallowing
      process. The "lentify" and "two times" ejection types also point to swallowing
      physiology alteration. There are functional correlation between organization and
      oral ejection. The oral organization has influence, not only in the quality of
      the oral ejection, but also, in the effective dynamics of the pharyngeal phase.

PMID- 15499420
TI  - [Comparative incidence of acute appendicitis in a mixed population, related to
      skin color].
AB  - BACKGROUND: Acute appendicitis is a very common surgical emergency, but its
      etiology and pathology remain incompletely understood. OBJECTIVE: To elucidate
      epidemiological aspects of acute appendicitis related to skin color, gender and
      age. METHODS: Five-hundred patients operated on for acute appendicitis, and other
      500 patients treated for different diseases and considered as a control group
      were studied at "Hospital das Clinicas", Federal University of Minas Gerais, Belo
      Horizonte, MG, Brazil. Gender, age and skin color were investigated. The results
      were compared by chi-square test. RESULTS: There was no prevalence related to
      gender. A significant prevalence of white patients (73.8%) was verified in this
      series. The number of white men with appendicitis was significantly higher than
      white men in the control group. The incidence of black patients with appendicitis
      was significantly lower than black patients of the control group. The mean age
      was 23.2 years old for the white patients with appendicitis and 32.3 years old
      for the black patients. CONCLUSIONS: The present paper shows an evident relation
      between appendicitis and white skin color.

PMID- 15499421
TI  - Sequential swallows have no influence on esophageal contractions of patients with
      iron deficiency anemia.
AB  - BACKGROUND: An experimental study showed that thyropharyngeal, cricopharyngeal
      and cervical esophageal muscles of rabbits with iron deficiency anemia had
      morphological changes similar to those observed in muscular dystrophy, causing
      myastenic changes in muscles involved in swallowing. Our hypothesis is that
      patients with iron deficiency anemia may have a decrease in esophageal
      contractions with successive swallows. PATIENTS AND METHOD: We studied the
      esophageal motility of 12 women with iron deficiency anemia aged 31 to 50 years
      (median 36 years) with serum iron from 11 to 40 mug/dL (median 21 mug/dL), and 13
      asymptomatic women aged 26 to 49 years (median 35 years) with serum iron over 60
      mug/dL. We used the manometric method with continuous perfusion. The esophageal
      contractions were measured at 3, 9 and 15 cm from the upper margin of a sleeve
      that straddled the lower esophageal sphincter. Each subject performed 10 swallows
      of a 2 mL bolus of water alternated with 10 swallows of a 7 mL bolus, with an
      interval of 30 seconds between swallows. We measured the amplitude, duration,
      velocity and area under the curve of contractions. RESULTS: There was no
      difference between the swallows of a 2 mL or 7 mL bolus. The amplitude, duration
      and area under the curve were lower in patients with iron deficiency than in
      asymptomatic volunteers, mainly in the proximal and middle esophageal body. There
      was no difference in velocity. Sequential swallows did not change contraction
      amplitude, duration, velocity or area under curve in patients and volunteers.
      CONCLUSION: Although the power of esophageal contractions was decreased in
      patients with iron deficiency anemia, sequential swallows did not cause further
      impairment.

PMID- 15499422
TI  - [Bowel preparation for colonoscopy with sodium picosulphate and magnesium citrate
      in children and adolescents].
AB  - BACKGROUND: The efficacy of colonoscopic examination depends directly on bowel
      cleansing preparation. There are few studies in the medical literature about
      bowel preparation in children. AIM: To determinate the efficacy of picosulphate
      sodium with magnesium citrate as a bowel preparation in children and adolescents.
      PATIENTS AND METHODS: In an open prospective and consecutive trial, we included
      all children above 1 year of age submitted to colonoscopy for different
      indications. All patients received the drug the day before the procedure and was
      allowed no solid food but a liberal intake of clear fluids. The adequacy of the
      preparation was graded as follows: gI--excellent, gII--good, gIII--fair and gIV-
      poor. RESULTS: Forty-six patients were included. The age ranged from 12 months to
      16.1 years (median = 6.6y), 54.3% were males. Bowel preparation was made
      according to instructions in 37/46 (80.4%) of patients, 9 patients did not adhere
      to diet of clear liquids and 22/46 (47.8%) had side effects. The adequacy of the
      bowel preparation was: gI in 41.3%, gII in 52.2%, gIII in 6.5% and none in gIV.
      CONCLUSION: Bowel preparation with picosulphate sodium and clear fluids provides
      an effective, practical method of preparing the bowel for colonoscopy in children
      and adolescents and could be recommended.

PMID- 15499423
TI  - [Dermatoglyphics of children with chronic constipation].
AB  - BACKGROUND: The dermatoglyphics can be used to study the participation of genetic
      factors in many diseases. There is controversy concerning the association between
      the dermatoglyphic pattern of digital arches and constipation. AIM: To compare
      the dermatoglyphic patterns among children with and without chronic constipation
      in relation to the dermatoglyphic patterns and characteristics of stools of their
      mothers. METHODS: Three groups of children aged from 2 to 12 years and their
      mothers were studied: 35 patients with severe chronic constipation, 45 children
      with mild chronic constipation and 51 children without constipation. The
      fingerprints were taken and evaluated by a datiloscopy technicist and classified
      in arch, radial loop, ulnar loop, whorl and others. RESULTS: Digital arches were
      found in 25.7% of severe constipated patients, 28.9% of mild constipated children
      and in 23.5% of controls. There was not a statistical significant association.
      Constipation was found in 51,9% (68/131) of the mothers. Arches were found in
      35.3% of the mother with constipation and in 42.9% of mothers without
      constipation. There was a slight association between constipation in children and
      in theirs mothers (Kappa coefficient = +0.16). CONCLUSION: The dermatoglyphics
      were not useful to identify the influence of genetic in constipation. There was
      not association between the dermatoglyphic pattern of digital arch and
      constipation both in children and in their mothers. Only a slight concordance was
      found between constipation in children and in their mothers.

PMID- 15499424
TI  - [The influence of the supine and prone positions in the esophageal pH monitoring
      in very low birth weight infants].
AB  - BACKGROUND: Scarce information is available on the effects of body's positioning
      in the number and the duration of gastroesophageal reflux episodes in very low
      birth weight infants. AIM: To evaluate the influence of prone compared to supine
      positions on the frequency and duration of acid gastroesophageal reflux episodes
      in very low birth weight infants and study the role of body position in the
      occurrence of exams with reflux index > or = 5% and > or = 10%. METHODS: Sixty
      one prolonged esophageal pH monitoring exams were retrospectively analyzed. The
      difference between the prone and supine position exam duration was not longer
      than 3 hours. The reflux index was evaluated for the total period of the exam
      (reflux index total) and for each period in the two positions. The total number
      of reflux episodes, the number of reflux episodes > 5 minutes and the longest
      reflux episode were evaluated for each period in the two positions. These
      parameters were compared in accordance with body positioning, for each one of the
      three reflux index total categories: reflux index total < 5%, > or = 5% and > or
      = 10%. The frequencies of exams with reflux index total > or = 5% and reflux
      index total > or = 10% were compared for both positions. RESULTS: The number of
      hours in prone (11.2 +/- 1.0) and in supine (11.2 +/- 1.1) position were not
      different. All the prone positions monitoring parameters were significantly lower
      than the supine ones, in the three reflux index total categories. In the supine
      position, 32.7% (20/61) and 27.8% (17/61) of the exams, which were normal in
      prone, became abnormal, taking into account reflux index > or = 5% and > or =
      10%, respectively, obtained for each position. CONCLUSIONS: In prone position,
      there is a significant decrease in number and duration of acid reflux episodes in
      very low birth weight infants. Supine position promotes a significant increase in
      the number of esophageal pH monitoring exams with reflux index > or = 5% and > or
      = 10%, making easier the diagnose of the gastroesophageal reflux disease.

PMID- 15499425
TI  - Effects on growth after portal hypertension induced in young rats.
AB  - BACKGROUND: Physical growth retardation in children with hypertension portal was
      observed regardless of schistosomiasis. It has been suggested that the shunt of
      portal blood through portosystemic collateral vessels would result in metabolic
      consequences that would lead to the physical growth deficit observed. AIM: Study
      the effects of hypertension portal in the growth of young rats. METHODS: The
      growth of 20 young rats, divided in the groups hypertension portal, n = 10, 103
      +/- 3.7 g and sham operation n = 10, 102.6 +/- 3.4 g was evaluated throughout 5
      weeks and the following parameters were under observation: quality of diet
      offered, diet ingestion, weight increase and urinary creatinine within 24 hours.
      At the end of the experiment, blood was taken for biochemical tests, prothrombin
      time and hematocrit and hypertension portal was measured. RESULTS/CONCLUSIONS:
      Rats with hypertension portal induced at early stages of their lives present
      growth delay in the first week after surgery recovering their growth rhythm in
      the next weeks, catching up with the sham animals. Differences related to urinary
      creatinine excretion, biochemical tests and hematocrit were not observed. Such
      results are evidence against the hypothesis that the hypertension portal induced
      in early stages of rats lives would cause delay in their growth.

PMID- 15499426
TI  - [Induced metabolic alterations due to experimental normothermic hepatic ischemia
      and the hepatoprotector effect of cyclosporin].
AB  - BACKGROUND: Hepatic transplantation is inevitably associated with periods of
      complete ischemia. However, the clamping of hepatic vascular pedicle is limited
      by the consequences of the post-ischemic injury to the liver. AIM: To determine
      the main metabolic alterations caused for the hepatic ischemia and the probable
      hepatoprotective effect cyclosporin. METHOD: Normothermic hepatic ischemia during
      60 minutes was induced in the rats. The time-course (0, 1, 6, 24 hours) of
      changes in blood and in the hepatic concentrations of lactate, pyruvate, glucose,
      ketone bodies and in the ratio of acetoacetate/3-hydroxybutyrate, as well as the
      cytoplasmic and mitochondrial redox state of the liver cells were determined. A
      group of animals was daily pre-treated with cyclosporine (10 mg/kg) during 4 days
      until the induction of hepatic ischemia, then they studied 1 hour after hepatic
      revascularization. Hepatic ischemia caused elevation in the concentrations of
      lactate in the liver, suggesting that a pronounced level of anaerobic metabolism
      occurred during the ischemia period. Liver ischemia promoted yet a fall in the
      concentration and in the ratio of ketone bodies (acetoacetate/3-hydroxybutyrate)
      in the arterial blood in the studied period of one hour post-revascularization,
      perhaps reflecting impairment of ketogenesis as a result of the ischemic injury.
      CONCLUSION: The treatment with cyclosporine cause elevation in the concentration
      of ketone bodies and in the ratio of acetoacetate/3-hydroxybutyrate in the
      arterial blood 1 hour after reperfusion of the liver, suggesting that these drugs
      may accelerate the recovery of the ischemic hepatic lesion with reactivation of
      ketogenesis.

PMID- 15499427
TI  - [Isolated Crohn's disease of the appendix as a source of enterorrhagia].
AB  - BACKGROUND: Crohn's disease confined to the appendix is relatively rare as a sole
      primary manifestation of the disease. Young people are more affected. The medical
      history and the physical examination are similar to the findings in acute
      appendicitis, but the manifestations are protracted. On physical examination
      there are signs of peritoneal irritation and an abdominal mass is palpable in the
      right iliac fossa. AIMS: To report a case of Crohn's disease confined to the
      appendix and presenting with enterorrhagia. The source of the bleeding was
      localized by colonoscopy. PATIENT: A 16-year old caucasian male without past
      history of gastrointestinal symptoms, presented with two episodes of
      enterorrhagia within a period of one year. In the second episode colonoscopy
      identified the appendicular ostium as the source of bleeding. RESULTS: At
      operation the cecum and terminal ileum were normal in thickness and texture, and
      an inflammatory appendix adherent to the omentum was removed. Microscopically
      there were non-caseating granulomas, intense infiltration of the wall with plasma
      cells, lymphocytes and macrophages. The patient has not suffered recurrence, and
      a colonoscopy realized 2 years after the operation did not show signs of Crohn's
      disease. CONCLUSION: This case, like others in the literature, appendectomy is
      curative, but a 5-year follow-up is mandatory. When a young patient presents with
      enterorrhagia, this diagnosis has to be considered.

PMID- 15499428
TI  - [Proposal of a questionnaire for the characterization of the prevalence of
      digestive symptoms in connective tissue diseases].
AB  - BACKGROUND: Connective tissue diseases may damage multiple organic systems,
      including digestive system. In this one, the degree of injury vary according to
      the associated disease. Despite the significant frequency of gastrointestinal
      involvement, there are few studies characterizing the prevalence of digestive
      symptoms in connective tissue diseases. Furthermore, most of the studies
      available are less detailed and based in personal experiences or reviews of
      records. AIM: To establish a reliable list of gastrointestinal symptoms found in
      the progressive systemic sclerosis, rheumatoid arthritis,
      polymyositis/dermatomyositis, mixed connective tissue disease and systemic lupus
      erythematosus, through a medical interview and a predefined questionnaire of
      symptoms. PATIENTS AND METHODS: There were studied 99 patients, 90% females, mean
      age 45 years. The whole group were composed of 35 rheumatoid arthritis, 26
      progressive systemic sclerosis, 21 systemic lupus erythematosus, 12
      polymyositis/dermatomyositis and 5 mixed connective tissue disease. Each patient
      was submitted to an interview with a well trained doctor and answered a
      structured questionnaire, containing 17 questions. RESULTS: It was found a high
      prevalence of digestive symptoms in all five connective tissue diseases searched.
      Many of them were present in more than 50% of the patients. Called special
      attention the detection of some manifestations neglected by the literature like,
      for example, fecal incontinence. Also, disagreeing with other authors, was the
      finding of multiple gastrointestinal manifestations associated with rheumatoid
      arthritis. It was particularly surprising the occurrence of dysphagia in one
      third of the rheumatoid arthritis group. CONCLUSIONS: The connective tissue
      diseases are usual causes of many gastrointestinal complaints. The use of an
      interview plus predefined questionnaire seems a very effective way to identify
      and characterize symptoms and is even sometimes able to uncover features unknown
      before. Finally, the lack of studies, specially updated studies, did not allow
      more comprehensive comparisons.

PMID- 15499429
TI  - [Efficacy of the dosing regimen of pantoprazole 40 mg, amoxicillin 1000 mg and
      clarithromycin 500 mg, twice daily for 7 days, in the eradication of Helicobacter
      pylori in patients with peptic ulcer].
AB  - AIM: This is an open label, multicenter trial to determine the efficacy of the
      association of pantoprazole, clarithromycin and amoxicillin to eradicate
      Helicobacter pylori in patients with peptic ulcer. MATERIAL AND METHODS: Seventy
      one patients (36 females, 35 males, average age 41.9 years) from three Brazilian
      university centers (located in the cities of Belo Horizonte and Porto Alegre),
      with peptic ulcers confirmed by endoscopy, and infections by H. pylori proven by
      at least two diagnostic testings were admitted in the trial. An association of
      pantoprazole 40 mg, clarithromycin 500 mg and amoxicillin 1.0 g was administered
      to patients twice daily for 7 days. RESULTS: By the end of treatment all patients
      were examined for digestive symptoms, presence of adverse events, and treatment
      adherence. Sixty days after the end of the treatment a new endoscopy with
      biopsies and respiratory function testing with 13C-urea breath test was performed
      in order to determine the eradication rates of that microorganism. Patients
      showing negative results at least in the 13C-urea breath test and in one other
      test (urease or histology) were considered H. pylori-negative. By the end of the
      trial, 60/69 (87%, CI 95% = 78.9-94.8) patients had the H. pylori eradicated in
      the per protocol analysis and 60/71 (84.5%, CI 95% = 76-92.9) in the intention-to
      treat analysis. One patient was withdrawn from the trial due to a diarrhea.
      Twelve (16.9%) patients showed adverse symptoms that were deemed as mild
      symptoms. CONCLUSION: Our conclusion is that the association of pantoprazole,
      amoxicillin and clarithromycin administered during 7 days is an effective and
      well-tolerated alternative as regards the eradication of H. pylori in patients
      with peptic ulcer in Brazil.

PMID- 15499430
TI  - [Health promotion and the epistemological sensitivity of 'community' as a
      category].
AB  - A discussion on the scope of "community" as a category in health promotion by
      means of its "epistemological sensitivity"--a reasoning tool based upon the
      epidemiological concept of "sensitivity", adjusted to the epistemological field-
      was carried out. A brief review of promotional health topics and a short
      description of the sociological usage of "community" according to Tonnies were
      performed. Issues regarding difficulties of defining contemporary communities are
      considered. Health promotion's leading approaches do not pay enough attention to
      crucial sociological concerns and philosophical standpoints. As a result, these
      approaches suffer from deep theoretical strain that weaken their premises and
      make corresponding interventions' results rather unsatisfactory.

PMID- 15499431
TI  - [Susceptibility of Aedes aegypti larvae to the insecticide temephos in the
      Federal District, Brazil].
AB  - OBJECTIVE: To study the susceptibility status of Aedes aegypti to the
      organophosphate insecticide temephos. METHODS: Samples of Ae. aegypti larvae were
      obtained, using ovitraps, from eight cities of the Federal District, central
      Brazil, in 2000 and 2001. Larvae were submitted to the diagnostic dose of 0.012
      mg/l temephos, as recommended by standard World Health Organization methodology.
      Field populations were tested in parallel with reference strains Rockefeller and
      DIVAL, from the Environmental Surveillance Directory (DIVAL) insectary. The
      concentration and purity of temephos solutions were verified by gas
      chromatography. Correlation calculations were performed using StatView - SAS
      Institute Inc., version 5. Student's t test was used for detecting differences in
      susceptibility, with significance levels of alpha=0.05. RESULTS: In 2000, Ae.
      aegypti larvae populations from Taguatinga, Guara, and Nucleo Bandeirante showed
      resistance to temephos, with mortality ranging from 54.1 to 63.4%. The
      populations from Gama, Planaltina, and Sobradinho showed altered levels of
      susceptibility (mortality ranging from 83.6 to 92.8%). The population from
      Ceilandia was the only susceptible one, with 98% mortality. In 2001, all
      populations tested were resistant (44.4 to 66.4% mortality). No significant
      correlation was found between the susceptibility of populations and the distance
      between the cities of origin, or the amount of insecticide applied in the years
      preceding the study. CONCLUSIONS: Ae. aegypti susceptibility to temephos is
      changing in the Federal District. It is essential to continue monitoring the
      resistance of this vector to insecticides in order to ensure the efficiency of
      programs aimed at vector control and at the protection of human health.

PMID- 15499432
TI  - [The color of death: causes of death according to race in the State of Sao Paulo,
      1999 to 2001].
AB  - OBJECTIVE: Assuming that ethnicity might be a basis for social differentiation
      and that such differences might represent vulnerability to sickness, this study
      attempts to verify whether race or ethnic origin have an effect on mortality
      patterns. METHODS: The Sao Paulo State death register was examined from 1999 to
      2001 in a contingence table of causes according to the 10th ICD and race or skin
      color categories (White, Black, Mulatto and others). Chi-square test was used to
      check the association between skin-color and cause of death; residual analysis
      was used to elicit statistically significant excessive occurrences when each
      category of cause of death and skin color was combined; and correspondence
      analysis was used to examine overall relations among all categories considered.
      RESULTS: A total of 647,321 valid death registers were analyzed, among which
      77.7% were of Whites, 5.4% of Blacks, 14.3% of Mulattoes and 2.6% of others. A
      significant association between skin color or race and cause of death was found.
      It may be observed that, although Blacks and Mulattoes present a similar death
      profile, on the contrary of Whites and others, which could be aggregated into a
      single category, the former appear in distinct positions on the multidimensional
      map presented. Except for mal defined causes, which characterize only the deaths
      of Blacks, the other causes of death within this group are common to both Blacks
      and Mulattoes, varying however, in intensity and as to the order in which they
      appear death. CONCLUSIONS: Analysis of mortality according to race or color
      revealed that death has a color. There is a White death, which has, among its
      causes, sicknesses, which, although variable, are nothing more than sicknesses.
      There's a Black death, which is not caused by sicknesses but by external causes,
      complications in labor and delivery, mental disorders and ill-defined causes.

PMID- 15499433
TI  - [Validity of self-reported hypertension and its determinants (the Bambui study)].
AB  - OBJECTIVE: Assessing the validity of self-reported hypertension and its
      determinants among adults living in the community was the objective of this
      study. METHODS: A simple random sample of residents in the city of Bambui, State
      of Minas Gerais, Brazil aged >18 years was selected. Three blood pressure
      measurements were performed in 970 inhabitants. Sensitivity, specificity as well
      as positive and negative predictive values of self-reported hypertension were
      assessed in relation to hypertension (mean blood pressure >90 or >140 mm Hg
      and/or present use of anti-hypertensive drugs). RESULTS: Sensibility and
      specificity of self-reported hypertension were 72.1% (95% CI: 69.3-75.0) and
      86.4% (95% CI: 84.3-88.6), respectively. Its prevalence was 27.2% (95% CI: 24.4
      30.1), being reasonably similar to the prevalence of hypertension (23.3%; 95% CI:
      20.7-26.1%). The validity of self-reported hypertension was higher among women,
      among individuals aged 40-59 and > or =60 years, among those who visited a doctor
      more recently (< two years) and among those with higher body mass index (>25
      kg/m2). CONCLUSIONS: The results of this study show that self-reported
      hypertension is an appropriate indicator of hypertension prevalence, even in a
      population not living in a large urban center.

PMID- 15499434
TI  - [Validation of methods for estimating HIV/AIDS patients' body fat].
AB  - OBJECTIVE: To validate different methods for estimating HIV/Aids patients' body
      fat: total body skinfold thickness, central (trunk) skinfold thickness,
      peripheral (limb) skinfold thickness, waist circumference (WC) and waist-to-hip
      ratio (WHR). Dual-energy X-ray absorptiometry (DEXA) and computed tomography of
      the abdomen (CTA) were used as the gold standard. METHODS: An analysis was done
      on 15 adult HIV/Aids patients (10 men and 5 women) who were being treated at an
      Aids clinic at a public university hospital, Sao Paulo, Brazil. Their total
      subcutaneous fat (TSF) was estimated from the sum of the thicknesses of the
      biceps, triceps, subscapular, midaxillary, suprailiac, abdominal and medial calf
      skinfolds. The central subcutaneous fat (CSF) was estimated by summing the
      subscapular, axillary, suprailiac and abdominal skinfold measurements. The
      peripheral subcutaneous fat (PSF) was estimated by summing the biceps, triceps
      and medial calf skinfold measurements. These were compared with Dexa. The WC, WHR
      and CSF were compared with CTA. In the statistical analysis, the Pearson
      correlation coefficient (r) and Mann-Whitney test were utilized. RESULTS: There
      was a correlation between fat mass measured by DEXA and by TSF, CSF and PSF, even
      after adjusting for age (r> or =0.80 for all). WC, WHR and CSF presented
      correlation with total abdominal fat measured by CTA, even after adjusting for
      age (r> or =0.80 for all). CONCLUSIONS: The methods for estimating body fat
      should be chosen according to the type of fat to be evaluated and can be used in
      research and healthcare services instead of DEXA and CTA for HIV/AIDS patients.

PMID- 15499435
TI  - [Prevalence of mental disorders in an urban area in Brazil].
AB  - OBJECTIVE: To detect the prevalence of mental disorders among the elderly
      residents of an urban area. METHODS: A sample of 327 elderly residents (60 years
      and older) of the city of Montes Claros, in northern Minas Gerais, was selected
      by means of probabilistic sampling, in multiple strata, within a homogeneous
      stratum. The sample unit was the home. Mental disorders were determined by means
      of the Short Psychiatric Evaluation Schedule (SPES). Univariate analysis was done
      via the chi-squared test and multivariate analysis via logistical regression.
      RESULTS: The estimated prevalence of mental disorders was 29.3%. Their presence
      was associated with female sex, number of illnesses, functional capacity and
      place of residence (shantytown/non-shantytown). CONCLUSIONS: Comparing the
      results with other community studies, the prevalence of mental disorders among
      the elderly in the urban area of Montes Claros was high and was associated with
      multiple illnesses, incapacity and poverty. This reality is a matter for concern
      because of its impact on quality of life relating to this population's health,
      and on healthcare services over the next few decades.

PMID- 15499436
TI  - [Epidemiologic surveillance and evaluation of meningitis hospital care].
AB  - OBJECTIVE: To analyze the clinical-epidemiological profile and in-hospital death
      predictors of infectious meningitis patients admitted to a public hospital.
      METHODS: There were studied 694 cases of meningitis notified and investigated by
      a public hospital's epidemiology service from 1986 to 2002, using the National
      Information System of Notifiable Diseases (SINAN) as part of the local routine of
      epidemiologic surveillance. Statistics analysis included multivariate logistic
      regression. RESULTS: The most frequent etiologies were: cryptococcal (12.3%; case
      fatality =37.7%); meningococcal (8.7%; fatality =13.3%); pneumococcal (7.2%;
      fatality =46%); tuberculous (6.1%; fatality =40.5%); staphylococcal (5.2%;
      fatality =38.9%), viral (5.5%; fatality =7.9%); Haemophilus (2.9%; fatality
      =20%). The proportion of cases of non-specified etiology was 38.8% (fatality
      =36%) and 17.3% were associated to HIV infection. It was found that 27.1% were
      nosocomial meningitis and 9.2% of the surviving cases had sequelae. The logistic
      regression model identified the following death predictors of infectious
      meningitis: etiology (reference: viral category) -- tuberculous, cryptococcal,
      staphylococcal, meningococcal, non-specified, other Gram-negative, Candida and
      pneumococcal; HIV co-infection; coma. Fever, vomiting and neck stiffness were
      associated to a lower odds of death. CONCLUSIONS: The high proportion of non
      specified etiology and high case-fatality may reflect problems in the hospital
      care process and/or case selection. The epidemiologic surveillance system
      operating at the hospital level was able to feedback the services with clinical
      indicators. The use of SINAN at the local level was considered useful and
      pertinent.

PMID- 15499437
TI  - [Impact of Haemophilus influenzae b (Hib) vaccination on meningitis in Central
      Brazil].
AB  - OBJECTIVE: To assess the impact of the Haemophilus influenzae b (Hib) conjugate
      vaccine in reducing the incidence of meningitis among children under five years
      old. METHODS: A 'before-after' design was used to compare Hib meningitis
      incidence rates in the pre-vaccine (July 1995 - June 1999) and post-vaccine (July
      1999 - June 2001) periods in the state of Goias, central Brazil. Bacterial
      meningitis case definition was based on World Health Organization criteria.
      Incidence rates of S. pneumoniae and N. meningitidis were used for comparison
      purposes. Chi-squared and Student's t tests were used for statistical analysis. P
      values below 0.05 were considered as statistically significant. RESULTS: 979
      children with acute bacterial meningitis were detected throughout the entire
      period. The incidence rate of Hib meningitis decreased from 10.8 (x10(5)) in the
      pre-vaccine period to 2.3 (x10(5)) in the 2nd year post vaccination, leading to a
      risk reduction of 78%, targeted to the 7-23 months age group (p<0.05). A total of
      65 cases of Hib meningitis were prevented. An increase in S. pneumoniae
      meningitis was observed. Vaccine failure was detected in one child. CONCLUSIONS:
      This study showed that mass immunization with Hib conjugate vaccine brought about
      an expressive decline in childhood Hib meningitis in Goias soon after the first
      year. Notwithstanding, an enhancement of surveillance using high-accuracy tools
      is essential to: (i) detect a possible reemergence of Hib; (ii) identify vaccine
      failure, and (iii) monitor changes in the H. influenzae serotype profile over
      time.

PMID- 15499438
TI  - Immunogenicity of WHO-17D and Brazilian 17DD yellow fever vaccines: a randomized
      trial.
AB  - OBJECTIVE: To compare the immunogenicity of three yellow fever vaccines from WHO
      17D and Brazilian 17DD substrains (different seed-lots). METHODS: An equivalence
      trial was carried out involving 1,087 adults in Rio de Janeiro. Vaccines produced
      by Bio-Manguinhos, Fiocruz (Rio de Janeiro, Brazil) were administered following
      standardized procedures adapted to allow blocked randomized allocation of
      participants to coded vaccine types (double-blind). Neutralizing yellow fever
      antibody titters were compared in pre- and post-immunization serum samples.
      Equivalence was defined as a difference of no more than five percentage points in
      seroconversion rates, and ratio between Geometric Mean Titters (GMT) higher than
      0.67. RESULTS: Seroconversion rates were 98% or higher among subjects previously
      seronegative, and 90% or more of the total cohort of vaccinees, including those
      previously seropositive. Differences in seroconversion ranged from -0.05% to 
      3.02%. The intensity of the immune response was also very similar across
      vaccines: 14.5 to 18.6 IU/mL. GMT ratios ranged from 0.78 to 0.93. Taking the
      placebo group into account, the vaccines explained 93% of seroconversion. Viremia
      was detected in 2.7% of vaccinated subjects from Day 3 to Day 7. CONCLUSIONS: The
      equivalent immunogenicity of yellow fever vaccines from the 17D and 17DD
      substrains was demonstrated for the first time in placebo-controlled double-blind
      randomized trial. The study completed the clinical validation process of a new
      vaccine seed-lot, provided evidence for use of alternative attenuated virus
      substrains in vaccine production for a major manufacturer, and for the
      utilization of the 17DD vaccine in other countries.

PMID- 15499439
TI  - [Phytoplankton community in a recreational fishing lake, Brazil].
AB  - OBJECTIVE: The assessment of water quality and phytoplankton community in
      recreational environments allows to setting management programs aiming at
      preventing potential harm to human health. The purpose of the present study was
      to describe phytoplankton seasonal changes in a freshwater system and their
      relation to water quality. METHODS: The recreational fishing lake is located in
      the southern area of the city of Sao Paulo, Brazil. Water samples were collected
      in three previously selected sites in the lake throughout a year and analyzed
      regarding floristic composition and physical and chemical parameters. RESULTS:
      The phytoplankton qualitative analysis revealed 91 taxa distributed among eight
      classes: Chlorophyceae, Cyanophyceae, Euglenophyceae, Zygnemaphyceae,
      Bacillariophyceae, Xantophyceae, Dinophyceae, and Chrysophyceae. Some physical
      and chemical parameters seemed to influence phytoplankton community behavior.
      Chlorophyceae development was favored by local conditions. Among the species of
      cyanobacteria identified, Microcystis paniformis, Cylindrospermopsis raciborskii,
      and Anabaena species were the most important due to their ability to produce
      toxins, posing a high risk to public health. CONCLUSIONS: Some physical and
      chemical parameters had an impact on the structure of phytoplankton community.
      The presence of Microcystis paniformis, Cylindrospermopsis raciborskii and
      Anabaena species indicates toxic potential and likelihood of public health
      problems unless there is constant monitoring. Further studies are recommended to
      prevent hazardous effects to the environment and public health.

PMID- 15499440
TI  - [Functional impact of hospitalization among elderly patients].
AB  - OBJECTIVE: To describe functional capacity changes of elderly during
      hospitalization and to assess the correlation of these changes at the time of
      hospital discharge and sociodemographics and clinical variables. METHODS: There
      were studied 94 patients aged 65 to 94 years admitted to a geriatric
      gerontological hospital unit of a school hospital. The first functional capacity
      evaluation (number of daily living activities impaired) of the elderly patients
      was carried out up to 24 hours after admission and the last one immediately after
      discharge. Routine therapeutic interventions were performed by an
      interdisciplinary health care team in the study period. Data was analyzed using
      Chi-square test (alpha< or = 0.05). RESULTS: Of all patient studied, 25.6%
      improved their functional capacity, 34.0% had not had functional changes, 19.1%
      had worsened functionally, and 21.3% died during the study period. A significant
      correlation was seen between functional deterioration and cognitive deficits,
      delirium, and low functional capacity at admission. CONCLUSIONS: Functional
      capacity is an important marker of health in hospitalized elderly. Functional
      improvement during hospitalization is associated to lesser impairment in daily
      activities at the time of admission and better clinical conditions.

PMID- 15499441
TI  - [Air pollution and respiratory diseases among children in the city of Curitiba,
      Brazil].
AB  - OBJECTIVE: To assess the effects of air pollution levels on respiratory morbidity
      among children from 1999 to 2000. METHODS: Daily records of health center
      attendance due to respiratory diseases among children were obtained from the
      public health system in Curitiba, State of Parana, Brazil. Daily levels of
      particulate matter (PM10), smoke, NO2 and O3 were obtained from both Parana State
      Environmental Institute and the Development Technology Institute, a non
      governmental agency. Daily measurements of temperature and relative humidity were
      obtained from the National Institute of Meteorology. Generalized additive Poisson
      regression models were used to assess the relationship between respiratory
      diseases and air pollution, controlling for long-term seasonality using loess (a
      non-parametric smoothing function), weather and weekdays. A significance level of
      5% was adopted in all the analyses. RESULTS: All pollutants presented an effect
      on respiratory diseases among children. An increase of 40.4 mg/m3 in the 3-day
      moving average of smoke was associated with an increase of 4.5% (95% CI: 1.5-7.6)
      in the attendance of children with respiratory diseases. CONCLUSION: The results
      suggest that air pollution promotes adverse effects on children's respiratory
      health even when pollutant levels are lower than the air quality standards.

PMID- 15499442
TI  - [Evaluation of hospital resources for perinatal assistance in Brazil].
AB  - OBJECTIVE: To verify the adequacy of hospital resources for perinatal care in
      Belo Horizonte, MG, Brazil in 1996. METHODS: This is a cross-sectional study
      conducted encompassing all the 28 maternity-hospitals in the city of Belo
      Horizonte, capital of the State of Minas Gerais, Brazil. A model of evaluation
      denominated "Niveis de Complexidade e Seguranca em Potencial de Unidades
      Perinatais de Hospitais-Maternidade" [Levels of Complexity and Potential Safety
      in Maternity-Hospitals]. This model is based on the evaluation of three major
      areas in the hospital: general structure, perinatal clinical infra-structure and
      resources available in perinatal units. Two scores involving these three areas
      were created. When evaluating low risk perinatal care, the score may sum to a
      total of 1,000 points. On the other hand, when high to medium perinatal risk care
      is considered, the score may sum to 2,000 points. Hosptals that scored more than
      500 points were classified in two levels: I-A and I-B (for low risk); and six
      levels I-A through III-B (for medium/high risk). RESULTS: Five hospitals were
      classified as level 0 according to the low risk score, that is, they were not
      considered adequate to assist any delivery. When the medium/high risk score was
      employed, a total of seven hospitals were considered inadequate to assist any
      delivery. CONCLUSIONS: This evaluation model was capable of classifying hospitals
      according to available infra-structure for perinatal care.

PMID- 15499443
TI  - [Occupation and mortality in the Brazilian Navy].
AB  - OBJECTIVE: To describe the distribution of mortality due to digestive tract,
      genitourinary and nervous system diseases according to occupation among Brazilian
      Navy servicemen. METHODS: This was an exploratory study of proportional mortality
      among male servicemen in the Brazilian Navy who died between 1991 and 1995. The
      study population comprises the entire contingent of servicemen during this same
      time period. Data were obtained from death certificates submitted in order to
      obtain dependents' pensions, and from the corresponding occupational histories of
      these individuals. Basic causes of death were coded in accordance with the
      International Classification of Diseases (9th Revision). RESULTS: Servicemen
      presented increased proportional mortality for liver diseases related to alcohol
      consumption (age-adjusted proportional mortality ratio, PMRadj=2.03; 95%
      confidence interval, CI: 1.26-3.00), pancreatitis (PMRadj=2.03; 95% CI: 1.06
      3.38), digestive hemorrhage (PMRadj=1.61; 95% CI: 1.10-2.23), chronic kidney
      diseases (PMRadj=2.82; 95% CI: 1.98-3.84), Parkinson's disease (PMRadj=3.00; 95%
      CI: 1.27-5.72) and degenerative brain diseases (PMRadj=2.88; 95% CI: 1.14-5.70),
      in relation to the reference population. A statistically non-significant
      association was observed between radar operators (PMR=6.50; 95% CI: 1.43-29.56)
      and nervous system diseases was observed. CONCLUSIONS: The results indicate the
      existence of possible occupational risk factors in the working environment of the
      Brazilian Navy, and the need for studies using quantitative measurement of such
      exposure.

PMID- 15499444
TI  - [Lead level, enamel defects and dental caries in deciduous teeth].
AB  - OBJECTIVE: To verify the relationship between lead concentration in the enamel of
      deciduous teeth and the presence of enamel defects and, consequently, with dental
      caries among preschool children. METHODS: The sample consisted of 329 preschool
      children in Piracicaba, State of Sao Paulo: 132 attending municipal kindergartens
      close to industrial plants and 197 attending kindergartens in non-industrial
      areas. This sample belonged to an initial study made between 2000 and 2001, in
      which the lead concentration was obtained by means of enamel biopsy. Oral
      clinical examination of the children from both regions was performed to verify
      the prevalence of enamel defects, using the Developmental Defects of Enamel (DDE)
      Index of the World Dental Federation (FDI), and of dental caries, using the
      decayed, missing and filled surfaces (dmfs) index of the World Health
      Organization. The chi-squared test and relative risk calculation were utilized in
      relation to a significance level of 5%, considering each region separately.
      RESULTS: Among the children from the non-industrial area, there was a higher
      proportion with dental caries among those with higher lead concentrations in
      deciduous teeth (p=0.02). This was not, however, observed among the children from
      the industrial area (p=0.89). There was an increased relative risk (RR) of caries
      among the children from the non-industrial area, but this was not seen among the
      children from the industrial area. No relationship was observed between the
      presence of lead and enamel defects. CONCLUSIONS: No data was found that would
      give evidence of a relationship between lead concentration and enamel defects in
      either of the areas studied. No relationship was found between lead and dental
      caries in the industrial area, thus emphasizing that more studies of such
      relationships are needed.

PMID- 15499445
TI  - Detection of pathogens from periodontal lesions.
AB  - OBJECTIVE: To comparatively detect A. actinomycetemcomitans and F. nucleatum from
      periodontal and healthy sites. METHODS: Subgingival clinical samples from 50
      periodontitis adult patients and 50 healthy subjects were analyzed. Both
      organisms were isolated using a trypticase soy agar-bacitracin-vancomycin (TSBV)
      medium and detected by PCR. Conventional biochemical tests were used for bacteria
      identification. RESULTS: A. actinomycetemcomitans and F. nucleatum were isolated
      in 18% and 20% of the patients, respectively, and in 2% and 24% of healthy
      subjects. Among A. actinomycetemcomitans isolates, biotype II was the most
      prevalent. Primer pair AA was 100% sensitive in the detection of A.
      actinomycetemcomitans from both subject groups. Primers ASH and FU were also 100%
      sensitive to detect this organism in healthy subject samples. Primer pair FN5047
      was more sensitive to detect F. nucleatum in patients or in healthy samples than
      primer 5059S. Primers ASH and 5059S were more specific in the detection of A.
      actinomycetemcomitans and F. nucleatum, respectively, in patients and in healthy
      subject samples. CONCLUSIONS: PCR is an effective tool for detecting periodontal
      pathogens in subgingival samples, providing a faster and safer diagnostic tool of
      periodontal diseases. The method's sensitivity and specificity is conditioned by
      the choice of the set of primers used.

PMID- 15499446
TI  - Exposure to larva migrans syndromes in squares and public parks of cities in
      Chile.
AB  - Between November 2001 and December 2002, 600 dog fecal samples were collected in
      main squares and public parks of 13 cities in Chile, from the extreme north to
      the extreme south of the country. The samples were processed in the laboratory by
      centrifugal sedimentation and the Harada-Mori methods. T. canis eggs were found
      in 12 cities. Detection rates ranged from 1.9 to 12.5% with an average of 5.2%.
      Seven percent of the samples had eggs and 9.5% had rhabditoid and/or filariform
      larvae of Ancylostomatidae. Strongyloides stercoralis were not found. Squares and
      public parks in Chile pose a potential risk of exposure to visceral, ocular,
      and/or cutaneous larva migrans syndromes.

PMID- 15499447
TI  - [Quality of life in renal transplant patients: impact of a functioning graft].
AB  - Objective measures to evaluate quality of life are gaining importance as an
      adjuvant in assessing therapeutic interventions. The study purpose was to compare
      quality of life in renal transplant patients with functioning graft and those who
      restarted dialysis after graft loss. Quality of life was measured using the World
      Health Organization Quality of Life questionnaire (WHOQOL-Bref). One hundred and
      thirty two patients were interviewed, and divided into two groups: group I, 100
      patients on regular follow-up in outpatient clinics and stable graft functioning;
      and group II, 32 patients who restarted dialysis after graft loss. The WHOQOL
      Bref showed better quality of life in those renal transplant patients with a
      functioning graft, especially regarding the physical and psychological domains
      assessed in the general questions. There were no differences between the groups
      in the social relationship and environmental domains. WHOQOL-Bref is an efficient
      tool and can be useful for better approaching these patients, not only on a
      medical basis.

PMID- 15499448
TI  - [Tyrophagus putrescentiae predating adult insects of Aedes aegypti and Aedes
      albopictus in laboratory].
AB  - The present study aimed at identifying a mite infesting a colony of Aedes aegypti
      and Ae. albopictus as well as investigating the source of infestation. The mite
      species was identified after it was mounted on slides in Hoyer's medium and
      examined under an optical microscope. It showed to be Tyrophagus putrescentiae.
      Fish and rabbit food samples were kept in an environmental chamber at 27 degrees
      C and 90% humidity for 21 days and were weekly examined. The presence of T.
      putrescentiae was only observed in rabbit food. It is assumed that T.
      putrescentiae had been introduced into the colonies through phoresy among guinea
      pigs, which were kept at the time near the insectary under favorable conditions
      for their development (28.7 degrees C, 72% humidity, photoperiod of 14L:10D
      hours).

PMID- 15499449
TI  - Control of Aedes aegypti with temephos in a Buenos Aires cemetery, Argentina.
AB  - The efficacy of a larvicide, temephos, for controlling Ae. aegypti was evaluated
      in a cemetery in Buenos Aires, Argentina. Breeding sites decreased from 18.4% in
      the first study period (Nov 1998 to May 1999, without temephos) to 2.2% in the
      second period (Nov 1999 to May 2000, two applications), and to 0.05% in the third
      one (Nov 2000 to May 2001, five applications). Ovitraps with eggs decreased from
      17% in the first period to 5.8% in the second period, and to 2.9% in the third
      one. Results suggest that, in Buenos Aires, Ae. aegypti populations are highly
      susceptible to temephos. It is recommended to limit the use of temephos to
      prevent potential epidemics rather than for routine control.

PMID- 15499450
TI  - [Case report of post-exhumation human rabies in the city of Sao Paulo].

PMID- 15499451
TI  - [Investigating a Rocky Mountain fever outbreak in the area of Campinas].

PMID- 15499453
TI  - [State governments support farmers and invest on food security].

PMID- 15499454
TI  - [Forum approach strategies to tackle drug adulteration].

PMID- 15499455
TI  - [Brazil builds up a network of scientists to investigate infection outbreaks in
      health services].

PMID- 15499456
TI  - [The paths of medical education].

PMID- 15499469
TI  - [Images in Medicine. Occlusion of the central vein of the retina after treatment
      with intravenous human immunoglobulin].

PMID- 15499470
TI  - [Retroperitoneal fibrosis: video laparoscopic treatment].

PMID- 15499471
TI  - [Short bowel syndrome in children -- treatment with home parenteral nutrition].

PMID- 15499472
TI  - [Bioethics and vulnerability: the doctor and the patient].

PMID- 15499473
TI  - [A new paradigm for the treatment of cancer].

PMID- 15499474
TI  - [Human papillomavirus (HPV) infection and its relation with squamous cell
      carcinoma of the mouth and oropharynx].
AB  - OBJECTIVE: To establish a connection between infection by the human papilloma
      virus (HPV) and development of malignant (squamous cell carcinoma) and benign
      lesions (epithelial hyperplasia papillomatosis and papilloma) of the oral cavity
      and oropharynx. METHOD: A retrospective study of 66 blades and paraffin blocks
      with biopsy tissue fixed with formalin. This material, collected in 2002, refers
      to a group of 44 men (66.7%) and 22 women (33.3%) with ages ranging from 11 to
      100 years, with confirmed diagnoses of squamous cell carcinoma in 38 cases, of
      epithelial hyperplasia papillomatosis in 20 cases and of papillomas in 8 cases.
      This material was analyzed by immunohistochemistry and the presence of viral DNA
      in the biopsy samples was determined. RESULTS: Presence of the viral DNA (HPV) in
      16 of the 38 cases of carcinoma (42.5%), 19 in 20 cases of hyperplasia (95%) and
      8 in 8 cases of papilloma (100%) was detected. CONCLUSION: The samples in this
      study show the predominant incidence of the HPV in the epithelial hyperplasia
      papillomatosis and papilloma in relation to squamous cell carcinoma. This last
      lesion, on the other hand, did not show statistical correlation to the HPV.

PMID- 15499475
TI  - [Evaluation of non-oncologist physician's knowledge and attitude towards cancer
      screening and preventive actions].
AB  - BACKGROUND: New cancer cases are most often diagnosed by non-oncologist
      physicians. It is therefore essential for all physicians to be aware of cancer
      preventive practices and use them appropriately with their patients. METHODS:
      Questionnaires were administered to 120 non-oncologist physicians of various
      specialties attending the "Faculdade de Medicina do ABC" who deal directly with
      adult patients. Replies were collected and classified as appropriate or not
      according to one of these three cancer prevention guidelines: INCA, American
      Cancer Society and Canadian Task Force. RESULTS: The percentage of replied
      questionnaires was 58.3% (70 questionnaires). Mean age of physicians was 33.9
      years; 57.1% were women and 10% smokers. Most of the current preventive practices
      adopted by the participating physicians (45.72% to 100%) regarding the most
      common and preventable tumors (breast, cervix, prostate, colon and rectum and non
      melanoma skin cancer) did not agree with any of the guidelines mentioned above.
      When questioned about possible impediments for the appropriate practice of cancer
      prevention, 82.86% reported absence of health education agents working with the
      population, 77.14% scarceness of knowledge or training concerning prevention, and
      70.15% lack of financial support for ordering tests. Frequently, whenever there
      was disagreement between the guidelines and the physician's current practices,
      preventive tests were ordered in excess of those recommended by the guidelines.
      CONCLUSIONS: Physicians had a tendency to order excessive laboratory tests, an
      action which can be related to lack of knowledge and to divergence among
      guidelines. A more intensive educational effort regarding cancer prevention,
      directed towards teaching physicians in training, seems to be warranted.

PMID- 15499476
TI  - [Prevalence of micro and macroangiopatic chronic complications and their risk
      factors in the care of out patients with type 2 diabetes mellitus].
AB  - BACKGROUND: Type 2 diabetes (DM2) has been related to the development of
      macroangiopatic [coronary heart disease (CHD), peripheral vascular disease (PVD)
      and stroke] and microangiopatic [retinopathy, nephropathy, and distal sensory
      neuropathy (DSN)] complications. The aims of this study were to analyze
      prevalence of complications in DM2 patients and to estimate their associated risk
      factors. METHODS: Cross-sectional study, including 927 out patients with DM2 from
      three medical centers in Rio Grande do Sul: Hospital de Clinicas de Porto Alegre
      (n = 475), Grupo Hospitalar Conceicao (n = 229) and Hospital Sao Vicente de Paula
      (n = 223). Of the patients 42% were male, mean age was 59 +/- 10 years and the
      median known duration of DM2 was 11 (5-43) years. Retinopathy was identified by
      direct fundoscopy; CHD by WHO questionnaire and/or abnormal ECG and/or perfusion
      abnormalities on myocardial scintigraphy; DSN by compatible symptoms and absent
      sensation on 10 g monofilament and/or tune fork; PVD by the presence of
      claudication and absent foot pulses; stroke by presence of sequels and history;
      and nephropathy by the urinary albumin excretion rate (>20 microg/min).
      Hypertension was defined by blood pressure (>140/90 mmHg) and/or use of
      antihypertensive drugs. Body mass index (BMI, kg/m2) and waist-to-hip ratio (WHR)
      were calculated. RESULTS: CHD was present in 36% and PVD in 33% of the patients.
      Among the microvascular, 37% had nephropathy (12% with macroalbuminuria); 48%
      retinopathy (15% proliferative retinopathy). DSN was present in 36%. Seventy
      three percent of the patients presented arterial hypertension. Cholesterol levels
      were >200 mg/dl in 64% and BMI > 30 kg/m2 in 36%. Twenty two percent of patients
      were smokers and 21% ex-smokers. CONCLUSION: Diabetic complications are frequent
      among out patients referring to general hospitals. Almost all patients presented
      at least one risk factor for cardiovascular disease, justifying the efforts for
      identification and adequate control.

PMID- 15499477
TI  - [Effects of splenectomy on peritonitis produced by a colonic injury: study in
      rats].
AB  - BACKGROUND: Study the effects of splenectomy on the intra-abdominal infection by
      bowel flora, consequent to a colonic injury in Wistar rats. METHODS: We used 64
      animals, 20 for Group A1 (normal with colon lesion left open), 22 for Group A2
      (normal with colon lesion sutured) and 22 for Group B (spleen removed). The
      animals were submitted to a laparatomy through a midline abdominal incision and
      peritonitis was induced by a colonic lesion in the colon previously distended
      with 2 ml of saline introduced in the rectum. Bacteriological studies of the
      abdominal wash obtained with a sterilized swab and microscopic studies of samples
      of the segment of the sutured colon obtained at 48 hrs, 96 hrs and on the 12 post
      op day, were made in each group. All rats were submitted to an autopsy on the day
      of death or on the 12th post op day when the survivors were sacrificed. RESULTS:
      Similar bacteria were found in the three groups. E. coli (100%); Enterococcus
      fecalis (97%); Klebsiela pneumoniae (70%); Citrobacter freundi (70%) and
      Enterobacter aglomerans (63%). In the first 96 hours the rats without spleen had
      a lesser inflammatory reaction when compared to the group with spleen. The
      leading cause of death was generalized peritonitis in the first 96 hours. There
      was a significant statistical difference in the mortality rate between Group B
      (80%), Group A2 (no mortality) and Group A1 (35%). CONCLUSION: There was a
      significant statistical difference in the mortality rate caused by peritonitis
      between the groups with splenectomy when compared to the group with no
      splenectomy.

PMID- 15499478
TI  - [Practice of precocious diagnosis for prostate cancer among professors of the
      school of medicine, Minas Gerais Federal University- Brazil].
AB  - BACKGROUND: The authors studied the practice of precocious diagnosis for prostate
      cancer among 289 professor-physicians of the School of Medicine, Minas Gerais
      Federal University, Brazil. METHODS: Replies on these preventive practices were
      received from 135 professor-physicians through a confidential questionnaire
      administered. RESULTS: Results show that 20.7% of the professor-physicians "fifty
      one years old or more" never had a prostate preventive exam and 36.2% never had a
      rectal touch. CONCLUSIONS: This data suggests the need for additional
      investigation and the attention of the health services.

PMID- 15499479
TI  - [Acute diarrhea: does mother's knowledge of the disease reduce admission of
      children under two years of age?].
AB  - OBJECTIVES: To analyze the relationship of mother's knowledge about signs of
      dehydration, causes and management of acute diarrhea with admission of children
      under two years of age with the disease. METHODS: A nested cross-sectional and
      case-control study was carried out with children who were admitted at the
      "Instituto Materno Infantil de Pernambuco" with acute diarrhea: and control
      children admitted with other diseases. Variables were: patient admission having
      or not acute diarrhea (dependent); social-economic condition, nutritional state;
      duration of breastfeeding; mother's knowledge about acute diarrhea and its
      management (independent). The Epi-info software, 6.0 was used for analysis.
      RESULTS: There was statistical association between patient admission with acute
      diarrhea and poor social-economic conditions (p = 0.01); malnutrition (p = 0.01);
      short time of breastfeeding (p = 0.01), lack of mother's knowledge about how to
      avoid dehydration (p = 0.05) and effectiveness of oral rehydration solutions (p =
      0.02). There was no statistical association with knowledge about causes, signs of
      dehydration or management of acute diarrhea. CONCLUSIONS: The study disclosed
      association between admission of children under two years of age with acute
      diarrhea and poor social-economic conditions; short time of breastfeeding,
      malnutrition, mother's lack of knowledge on how to avoid dehydration and
      effectiveness of oral rehydration solutions. Data suggests that lack of mother's
      knowledge reflects poor social-economic conditions.

PMID- 15499480
TI  - [Human papillomavirus oncogenicity and grade of anal intraepithelial neoplasia in
      HIV positive patients].
AB  - OBJECTIVE: We decided to evaluate if grade of anal intraepithelial neoplasia
      (AIN) was associated to the HPV type in HIV positive patients, since this group
      of patients has immunodeficiency over long periods. We identified HPV types by
      PCR (polimerase chain reaction) and histological examination to determine the AIN
      grade in 39 HIV positive males with anal condylomata acuminata. RESULTS: We
      observed high grade AIN (HAIN) in 9 (23.1 percent) and low grade AIN (LAIN) in 30
      patients (76.9 percent). The most frequent HPV types were 6 and 11 (64 percent)
      and oncogenic types 16, 18 and 31 appeared in 20.5 percent of patients. We could
      not identify viral type in four patients (10.2 percent) despite tests revealing
      presence of viral deoxiribonucleic acid. Comparing AIN grades with viral types we
      observed that non-oncogenic types can also be associated with HAIN lesions.
      CONCLUSION: These results allowed us to conclude that both oncogenic and non
      oncogenic HPV types can be associated with HAIN lesions in HIV positive patients.

PMID- 15499481
TI  - [Hematological features and expression profile of myeloid antigens of acute
      promyelocytic leukemia patients: analysis of prognostic factors for development
      of the retinoic acid syndrome].
AB  - BACKGROUND: Acute Promyelocytic Leukemia (APL) is characterized by its good
      response to treatment with all trans retinoic acid (ATRA). However, some patients
      receiving ATRA develop a serious complication called retinoid syndrome (RS). The
      objective of this study was to compare the hematological and immunophenotypic
      features of APL patients who developed RS with those who did not. METHODS: We
      reviewed the medical records, roentgenograms, peripheral blood smears and bone
      marrow aspirates from 71 APL patients. Immunophenotypic analyses were available
      in 56 of these cases. Eight cases of RS were detected, whose clinical
      presentation was characterized by respiratory distress (n = 8), impairment of the
      renal function (n = 2), fever (n = 5), weight gain (n = 3), edema (n = 3) and/or
      pleural effusion (n = 5). The following variables were compared in patients with
      and without RS: hemoglobin levels, leukocyte and platelet counts, frequency of
      hypergranular and variant morphological subtypes, percentages of CD33+, CD13+,
      CD117+ blasts in the bone marrow, fluorescence intensity and variation of these
      markers in the leukemic cells, expressed as the median channel of fluorescence
      (MCF) and fluorescence coefficient of variation (CV), respectively. RESULTS: RS
      incidence was 11.26% and the average time for syndrome development was 11.5 days
      after starting ATRA treatment. All patients presented acute respiratory distress.
      Other symptoms included fever, weight gain, edema and renal insufficiency. The
      main radiological findings were ground glass opacities, increased vascular
      pedicle and peribronchial cuffing. There was no significant correlation between
      the variables selected and the risk of development of RS, however the Odds Ratios
      for patients presenting MCF for CD117 > 30 ua and CV for CD33 < 50 were of 7.14
      (P = 0.08) and 7.86 (P = 0.06), respectively. CONCLUSIONS: The incidence, as well
      as the clinical, radiological and laboratory features of RS in this group of
      Brazilian APL patients were similar to those described in literature. None of the
      variables studied were significantly correlated to a higher risk of developing
      RS.

PMID- 15499482
TI  - [Aspects of the pregnancy and post delivery of adolescents with rheumatic fever].
AB  - BACKGROUND: To evaluate the incidence and follow-up of pregnancy among
      adolescents with rheumatic fever (RF) attended at the authors' service. METHODS:
      A retrospective evaluation was undertaken of 510 patients with a diagnosis of RF
      according to records from 1983 to 2001. RESULTS: We evaluated 510 patients, 123
      (43%) were female adolescents. Sixteen (13%) patients became pregnant during this
      period, with a total of 19 gestations (one presented two gestations and another
      three); 14 realized the prenatal care appropriately. Age of the first gestation
      ranged from 14 to 19 years (mean 16.7); and age at the beginning of sexual
      activity ranged from 13 to 18 years (mean 15.2). Mitral insufficiency occurred in
      15 cases associated with aortic insufficiency in 5. Intercurrent disease during
      prenatal care was observed in two patients: in one there was recurrence of RF
      with chorea and in the other HIV infection. Vaginal delivery occurred in seven
      adolescents, forceps delivery in three and cesarean in four: one with HIV, one
      with twin pregnancy and two with functional dystocia. Thirteen newborn were
      adequate for gestational age and only the twins were premature. In the
      postpartum, one patient presented infection in the surgical incision and another
      had mammary abscess. No patient reactivated RF in childbirth or postpartum.
      CONCLUSIONS: Pregnancies did not present cardiac decompensation, there was
      however predominance of mild valvulitis. Precocious sexual activity and greater
      incidence of pregnancy among adolescents are realities in the pediatric
      rheumatology clinics; consequently there is a need for improved orientation in
      relation to sexuality and use of birth-control methods in the routine of such
      services.

PMID- 15499483
TI  - [Detection of induced neoplastic lesions in the oral mucosa of hamsters using
      fluorescence spectroscopy].
AB  - OBJECTIVE: This work analyzes use of the Laser Induced Fluorescence Spectroscopy
      technique for characterization of normal and neoplastic tissue in the oral mucosa
      of hamsters, with potential to diagnose neoplastic tissue in vivo. METHODS:
      Carcinogen DMBA was applied to the right cheek of 31 hamsters weighing 150 +/-
      10g, three times per week during 12 weeks. One animal was kept as a control
      (without application of the drug). At the end of this period, the animals were
      submitted to fluorescence spectroscopy excited by an argon laser (488nm)
      connected to an optical fiber cable. Tissue autofluorescence was analyzed by a
      spectrograph and a CCD camera with 1024X256 pixels covering the spectral range of
      550nm to 700nm. Fluorescence emission spectra were collected in the induced
      region and normal counter side cheek of all the animals and also in the control
      animal. After spectroscopy, biopsy was carried out for histopathological
      analysis. Two diagnosis algorithms, one based on the ratio of spectral regions
      and another based on Principal Components Analysis (PCA) were implemented.
      RESULTS: Spectral analysis had demonstrated existence of an intense peak in the
      region of 630nm in neoplastic tissues (attributed to protoporphyrin IX) when
      compared to the normal tissue. The algorithm based on the ratio of two spectral
      regions had 100% of sensitivity and specificity. The algorithm based on the PCA
      had 94% and 100% of specificity and sensitivity, respectively. CONCLUSIONS: This
      work indicates that tissue autofluorescence may be used as a non-invasive
      technique for diagnosis of the neoplastic oral mucosa.

PMID- 15499484
TI  - [Sentinel node study with patent blue in cervical cancer].
AB  - OBJECTIVE: The purpose of this study was to determine the feasibility of sentinel
      node identification in patients with invasive cervix cancer undergoing radical
      hysterectomy and pelvic lymphadenectomy using intraoperative lymphatic mapping
      with patent blue dye. METHODS: Fifty one patients wtih Figo I and II cervical
      cancer were submitted to radical hysterectomy and pelvic lymphadenectomy. The
      patent blue V was injected around the tumor before beginning surgery. At the time
      of pelvic lymphadenectomy, lymph nodes with obvious uptake of the dye were
      separated from the remainder of the lymphadenectomy specimen. RESULTS: Sentinel
      nodes were detected in 32 of the 51 patients. Four cases of false negative were
      observed. The specificity, sensitivity, positive predictive value and negative
      predictive value were 38.6%, 42.8%, 10% and 80.9%, respectively. CONCLUSIONS:
      Identification of sentinel node with patent blue dye is feasible in cervical
      cancer. A larger series will be required to establish sentinel detection in
      cervical cancer for further therapy concepts and planning.

PMID- 15499485
TI  - [Study on the effectiveness of brief intervention for alcohol and other drug use
      directed to adolescents in a primary health care unit].
AB  - OBJECTIVE: The main purpose of this study was to evaluate the effectiveness of a
      brief intervention and a preventive orientation on the use of alcohol and other
      drugs directed towards adolescents. METHODS: Ninety nine youths who sought
      medical assistance in an out patient service specialized in adolescents were
      classified, according to their level of consumption of substances, into users
      during the last month (UM) or non users during the last month (NUM). Each of
      these was divided into four groups: a control group of users in the last month
      (COUM), a control group of non users in the last month (CONUM), a Brief
      Intervention group (BI--in case they were regular users) and a Preventive
      Orientation group (PO--in case they were non users in the last month). The
      preventive orientation lasted 2-3 minutes and the brief intervention took about
      20 minutes, both followed a structured schedule. All participants were followed
      up and evaluated for a 6 months period. RESULTS: In the 6-month follow-up, a
      significant increase in cannabis, alcohol and tobacco consumption, as well as in
      the intensity of related-problems, was observed in the CONUM group. The increase
      of alcohol and tobacco consumption observed in the PO group had a significantly
      lesser frequency and lower intensity than in the CONUM group. Moreover, no
      increase in cannabis consumption was observed in this group. The BI group showed
      a significant reduction in the number of users during the last month with respect
      to most substances, as well as in relation to substance-related problems.
      CONCLUSION: Our results confirm that a single brief intervention session is
      effective in reducing consumption of psychoactive substances in adolescents.
      Although influence of other factors could not be discarded, preventive
      orientation reduced the increase of cannabis consumption but increased use of
      tobacco and alcohol. Further and more in depth studies are required to evaluate
      the usefulness of preventive programs on alcohol and other drug consumption, in
      order to bring to light more effective and comprehensive approaches.

PMID- 15499486
TI  - [Therapeutic approach of hereditary angioedema].
AB  - PURPOSE: Hereditary Angioedema was first described by William Osler in 1888 and
      it is caused by a hereditary or acquired deficiency of C1 esterase inhibitor (C1
      INH). Treatment is indicated for acute attacks or prophylaxis of angioedema which
      occur in the subcutaneous tissue respiratory or gastrointestinal tracts.
      Treatment includes attenuated androgens, inhibitors of kininogen or plasminogen,
      like tranexamic acid or e-aminocaproic acid and the administration of C1-INH
      concentrate. We describe the peculiarities of the treatment chosen for 10
      patients (4 families) with HAE and their evolution. METHODS: Ten patients (1-38
      years old) with HAE were diagnosed by clinical history and laboratory evaluation.
      The following tests were performed for the complement system: C1-INH, C4 and C3
      levels and hemolytic assay (CH50 and APH50) for the classic and alternative
      pathways. Treatment was initiated considering severity of symptoms, age, gender
      and therapeutic response of the patient. RESULTS: Clinical evaluation showed:
      4/10 patients with recurrent subcutaneous edema; 3/10 with previous laryngeal
      edema and 3/10 with sporadic symptoms. Different severity of symptoms was
      verified in the same family. The laboratory evaluation detected: low C1-INH
      levels (10/10); low serum C4 level (8/10); undetectable CH50 (3/10) and low CH50
      levels (6/10); low APH50 levels (2/10). Six out of ten patients did not receive
      any specific treatment and 2 of them had high risk of asphyxia. One adolescent
      had been controlled with e-aminocaproic acid, one child had been changed from
      danazol to tranexamic acid, a 30 year old female patient had received oxandrolone
      and a 38 year old man had been treated with danazol. CONCLUSIONS: Although HAE is
      caused by the same defect and affects members of the same family, various
      approaches have been taken to treat these patients. We observed different
      alternatives of prophylactic therapy for HAE, of which some did not require drug
      therapy.

PMID- 15499487
TI  - [Cytomegalovirus retinitis in pediatric patients with AIDS receiving highly
      active antiretrovirus therapy].
AB  - BACKGROUND: To describe three cases of cytomegalovirus retinitis occurring in HIV
      infected children taking protease inhibitors combined with transcriptase
      inhibitors (HAART). METHODS: Three cases of HIV-infected children taking highly
      active antiretrovirus therapy (HAART) underwent an ocular examination at a
      university referral center-UNIFESP. RESULTS: The average age was 6 years (10
      months to 13 years old), and all of them were C3 (CDC-Atlanta-EUA 1994). Median
      CD4 cell count and plasma HIV RNA were 67 cells/mm3 (43-98 cells/mm3) and 190.000
      copies/ml (53.600-460.000 copies/ml). The three patients presented HAART failure
      and all of them were treated with anti-CMV agents without success. CONCLUSION:
      The unprecedented benefits resulting from highly active antiretroviral therapy
      (HAART) have been well described. However, treatment failure has become
      increasingly complex, because of the aggressive forms of opportunistic diseases
      like CMV retinitis, despite anti-CMV agents. Prompt diagnosis and treatment are
      essential to minimize the risk of long-term loss of vision for these infected
      children.

PMID- 15499488
TI  - [Immunoexpression of c-erbB-2 in intraductal proliferative lesions of the female
      breast].
AB  - OBJECTIVES: Genetic modifications are related to genesis and development of
      cancer. Neoplasias in various organs express the c-erbB-2 oncogene. In
      intraductal proliferations of the breast it has been assessed as a risk factor
      for subsequent development of carcinoma. The c-erbB-2 immunoexpression in
      intraductal epithelial proliferations and the relationship with histopathological
      characteristics of ductal carcinoma in situ (DCIS) were evaluated. METHODS: File
      material from 88 women, which were tissue samples formalin-fixed, paraffin
      embedded blocks, was used. Of these 51 presented with DCIS and 37 with ductal
      hyperplasia without atypia. Ages of the women ranged from 35 to 76 years. All
      cases were reviewed and nuclear grade, presence of necrosis, preponderance of
      histological subtype and its extension were verified. Specimens were obtained for
      the c-erB-2 immunohistochemical study of 84 of the women in question. RESULTS: No
      expression of the oncogene was verified in the hyperplasias without atypias and
      in tissues adjacent to all tissue samples. Expression of c-erbB-2 was verified in
      9 (19.1%) of the DCIS (p = 0.0001). Immunoexpression was not related to the
      extension of the lesions. The c-erbB-2 immunoexpression in DCIS was correlated to
      the histological subtype (p = 0.019), necrosis (p = 0.0066), nuclear grade (p =
      0.0084) and Van Nuys Classification (p = 0.039). CONCLUSIONS: Expression of c
      erbB-2 was significant in proliferative lesions with risk (DCIS) and was
      correlated to histopathological characteristics: high nuclear grade, presence of
      necrosis and comedy subtype. There was no expression in the hyperplasias without
      atypias and adjacent tissues.

PMID- 15499489
TI  - [Short bowel syndrome in children--treatment with home parenteral nutrition].
AB  - BACKGROUND: In 1979 the author first utilized the method of home parenteral
      nutrition in a child in Brazil. The purpose of this paper is to present the
      experience, during the last 23 years, of treatment of children with short bowel
      utilizing home parenteral nutrition. METHODS: Nineteen children with short bowel
      syndrome (resection of more than 75% of total intestinal length) were initially
      treated in the hospital and then nutrition therapy was continued at home. Total
      duration of nutrition therapy ranged from 4 months to 4 years and a half, while
      periods of home nutrition therapy ranged from 1 week to 4 years (median 8
      months). Complete nutrition mixtures containing amino acids, glucose, lipid
      emulsion, electrolytes, vitamins and micro-elements were administered through
      Broviac or Hickman central venous catheters. Solutions were infused during the
      day or the night according to preference of the parents. RESULTS: In all cases
      weight gain, growth and development similar to normal children under oral
      nutrition were verified. Catheter occlusion, liver dysfunction and sepsis related
      to the catheter were the most frequent complications. Seven children (37%) are
      alive and treatment free. Twelve children died (ten of them with resection of the
      entire small bowel and cecum), 11 due to parenteral nutrition complications (nine
      due to catheter sepsis and two due to massive pulmonary embolization) and one
      child died with neurological complications after a combined liver and small bowel
      transplantation. CONCLUSION: Home parenteral nutrition is sometimes the only
      therapeutic choice for children with short bowel syndrome and promotes a maximal
      level of comfort to the patient and to the parents. Furthermore it reduces the
      period of hospitalization, while adaptation of the remaining small bowel occurs
      with maintenance of the nutritional status by oral route.

PMID- 15499490
TI  - [Statement of fair retribution in medical oaths].
AB  - BACKGROUND: to determine if Medical Oaths from different times include the
      statement of the physician to request from patients a fair retribution for
      his/her medical services. METHODS: Fifty Medical Oaths found in articles and
      publications were analyzed. In accordance with their corresponding dates, the
      Oaths were grouped as ancient /medieval (12), and modern/contemporary (38).
      RESULTS: Of the fifty, only three specifically included the statement of fair
      retribution. Two of the three were medieval and belonged to the School of
      Medicine of Montpellier. The other text was modern (Amato Lusitano's Oath). Four
      writings showed statements regarding medical assistance to the poor. Eleven
      pledges indirectly stated that no earnings from other activities and/or relations
      were obtained. CONCLUSIONS: Ancient oaths emphasize fair retribution, no
      discrimination in medical assistance based on payment possibilities, and gain of
      honest earnings. Modern oaths generally do not include these topics and very few
      mention that the medical profession should not be exercised merely for material
      purposes. Despite the above, physicians should respect the limits of their
      obligations and should be committed to assist without discriminating,
      particularly without taking into consideration their patient's financial
      possibilities. Therefore their fees should not be excessive for the services
      rendered.

PMID- 15499491
TI  - [Correlation between laparoscopic aspects and glandular hystological findings of
      peritoneal endometriotic lesions].
AB  - OBJECTIVE: To evaluate the correlation between laparoscopic aspects and glandular
      hystological findings of peritoneal endometriosis to understand the theory of
      evolution of endometriosis. METHODS: Sixty seven women with peritoneal
      endometriosis were submitted to laparoscopy. Peritoneal biopsy was taken from the
      typical (puckered black) and atypical endometriotic implants. The different
      aspects of endometriosis were classified as follows: red lesions (group V), black
      lesions (group N) and white lesions (group B). Hystological sections were
      examined according to a standardized protocol. The hystological parameters used
      were: functional characteristics of glandular epithelium, presence of
      intraluminal debris, occurrence of mitosis and stroma/gland ratio. RESULTS:
      Functional characteristics of glandular epithelium showed statistically
      significant association among groups. Secretory epithelium was found in 68.4 % of
      group V, in 15.8% of groups N & B, while not characteristic epithelium was found
      in 19.4% of red lesions, 38.7% of black lesions and 41.9% of white lesions.
      Proliferative epithelium was found in 50% of group B patients and in 25% of
      groups V & N (p=0.011). Regarding intraluminal debris, there were also
      statistically significant differences among the groups, present in 58.4% of group
      N, 33.3% of group B and 8.3% of group V (p=0.016). There was no statistical
      difference between occurrence of mitosis (P=0.428), nor in the stroma/gland ratio
      (p=0.159). CONCLUSION: Association between functional activity and red lesions
      and low activity in black and white lesions, regarding the hystological
      characteristics of the glandular epithelium analyzed in this study shows the
      importance of the theory of evolution of endometriosis. This was also
      demonstrated by presence of intraluminal debris in the study groups.

PMID- 15499492
TI  - Polar organic chemical integrative sampling and liquid chromatography
      electrospray/ion-trap mass spectrometry for assessing selected prescription and
      illicit drugs in treated sewage effluents.
AB  - The purpose of the research presented in this paper was twofold: (1) to
      demonstrate the coupling of two state-of-the-art techniques: a time-weighted
      polar organic chemical integrative sampler (POCIS) and microliquid chromatography
      electrospray/ion-trap mass spectrometry and (2) to assess the ability of these
      methodologies to detect six drugs (azithromycin, fluoxetine, omeprazole,
      levothyroxine, methamphetamine, methylenedioxymethamphetamine [MDMA]) in a real
      world environment, e.g., waste water effluent. In the effluent from three
      wastewater treatment plants (WWTPs), azithromycin was detected at concentrations
      ranging from 15 to 66 ng/L, which is equivalent to a total annual release of 1 to
      4 kg into receiving waters. Detected and confirmed in the effluent from two WWTPs
      were two illicit drugs, methamphetamine and MDMA, at 2 and 0.5 ng/L,
      respectively. Although the ecotoxicologic significance of drugs in environmental
      matrices, particularly water, has not been closely examined, it can only be
      surmised that these substances have the potential to adversely affect biota that
      are continuously exposed to them even at very low levels. The potential for
      chronic effects on human health is also unknown but of increasing concern because
      of the multiuse character of water, particularly in densely populated, arid
      areas.

PMID- 15499493
TI  - Use of zeolite for removing ammonia and ammonia-caused toxicity in marine
      toxicity identification evaluations.
AB  - Ammonia occurs in marine waters including effluents, receiving waters, and
      sediment interstitial waters. At sufficiently high concentrations, ammonia can be
      toxic to aquatic species. Toxicity identification evaluation (TIE) methods
      provide researchers with tools for identifying aquatic toxicants. For identifying
      ammonia toxicity, there are several possible methods including pH alteration and
      volatilization, Ulva lactuca addition, microbial degradation, and zeolite
      addition. Zeolite addition has been used successfully in freshwater systems to
      decrease ammonia concentrations and toxicity for several decades. However,
      zeolite in marine systems has been used less because ions in the seawater
      interfere with zeolite's ability to adsorb ammonia. The objective of this study
      was to develop a zeolite method for removing ammonia from marine waters. To
      accomplish this objective, we performed a series of zeolite slurry and column
      chromatography studies to determine uptake rate and capacity and to evaluate the
      effects of salinity and pH on ammonia removal. We also assessed the interaction
      of zeolite with several toxic metals. Success of the methods was also evaluated
      by measuring toxicity to two marine species: the mysid Americamysis bahia and the
      amphipod Ampelisca abdita. Column chromatography proved to be effective at
      removing a wide range of ammonia concentrations under several experimental
      conditions. Conversely, the slurry method was inconsistent and variable in its
      overall performance in removing ammonia and cannot be recommended. The metals
      copper, lead, and zinc were removed by zeolite in both the slurry and column
      treatments. The zeolite column was successful in removing ammonia toxicity for
      both the mysid and the amphipod, whereas the slurry was less effective. This
      study demonstrated that zeolite column chromatography is a useful tool for
      conducting marine water TIEs to decrease ammonia concentrations and characterize
      toxicity.

PMID- 15499494
TI  - The effects of sieving and spatial variability of estuarine sediment toxicity
      samples on sediment chemistry.
AB  - In 1998, we conducted a field-validation study of the chronic 28-day whole
      sediment toxicity test with Leptocheirus plumulosus in Baltimore Harbor, MD, an
      area where this amphipod is indigenous. This study included an evaluation of the
      effect of sieving on sediment chemical concentrations and the use of field
      replicates, or separate grabs from the same site, which provided an estimation of
      within-site chemical and toxicologic variability. Six stations in Baltimore
      Harbor, MD, were included in this evaluation. Chemical analysis of two separate
      unsieved field replicates from the six sites indicated that, overall, the
      chemical concentrations of replicates within each site were similar, especially
      for metals. Organic contaminants particularly total PCBs, had the highest
      variability between replicates. Chemical variability did not appear to be related
      to differences in organic carbon content or grain size or to variability in
      toxicologic end points. Results supported the use of composite samples in
      sediment toxicity tests. In addition, in most cases, sieving had little effect on
      sediment chemistry. For the metals and trace elements, only selenium showed a
      substantial change after sieving, with some samples increasing after sieving and
      others decreasing. Concentrations of acid-volatile sulfide (AVS) increased 194.6%
      at one station after sieving, although in most other cases, AVS and
      simultaneously extracted metals remained relatively unchanged. As expected,
      concentrations of organics generally decreased after sieving, but in the majority
      of cases this decrease was small (i.e., coefficient of variation < or = 25%).
      Total benzene hexachloride and total chlordanes had the greatest changes, whereas
      polychlorinated biphenyl concentrations decreased at only two stations after
      sieving. Concentrations of polyaromatic hydrocarbons showed little change after
      sieving. These changes in sediment chemistry due to sieving must be viewed in the
      larger context of the potentially confounding effects that indigenous organisms
      may have on the interpretation of test results from whole-sediment toxicity
      tests.

PMID- 15499495
TI  - Toxicity and estrogenic activity of a wastewater treatment plant in Northern
      Italy.
AB  - Many xenobiotics, widely diffused in the environment, have the potential to
      disrupt the delicate endocrine system balance of wildlife and humans. Substances
      showing hormone-like actions in living organisms are defined endocrine-disruptor
      chemicals and they may mimic, block, or interfere with the synthesis, release,
      transport, elimination, and binding of natural hormones. Different ecotoxicologic
      studies were applied to screen for the discharge of estrogenic and toxic
      substances into the aquatic environment from a small industrial wastewater
      treatment plant based in Northern Italy. Samples of wastewater (3 L) were taken
      at three different periods during the year from different points of the plant's
      process: three phases of treatment, and effluent. Untreated samples (1 L) were
      assayed with two toxicity tests: Microtox and Daphnia magna. A simplified
      proliferation test using human estrogen receptor-positive MCF-7 breast cancer
      cells (E-screen assay) was performed on 2-L samples after solid-phase extraction
      for the determination of total estrogenic activity; the presence of estrogenic
      substances was evaluated by measuring the proliferation rate in cells exposed to
      samples. The results of the Microtox assay employing the marine bacterium Vibrio
      fischeri were compared with data obtained from whole-effluent toxicity testing
      methods employing D. magna. Toxicity was found only for the influent point. The
      proliferative effect of the five points, relative to the positive control 17beta
      estradiol (relative proliferation effect), was between 2.4% and 39%, and the
      17beta-estradiol equivalent concentrations were between 0.06 and 3.94 ng/L. A
      first comparison between results from toxicity load and estrogenic activity was
      performed. At all process points, the effluent samples were considered acceptable
      (taking only toxicity into account), but we demonstrated that they had estrogenic
      activity in the river water indicating an input of estrogenic substances by way
      of the treatment plant.

PMID- 15499497
TI  - Effects of a chronic dietary exposure of the honeybee Apis mellifera
      (Hymenoptera: Apidae) to imidacloprid.
AB  - Previous studies have shown that imidacloprid and insecticidally active
      imidacloprid plant metabolites are rapidly metabolized by honeybees. Accordingly,
      no striking differences were expected between the acute and the chronic dietary
      toxicity of imidacloprid to honeybees. More recently, however, an unexpectedly
      high chronic dietary toxicity to honeybees was reported for imidacloprid and
      imidacloprid plant metabolites, and a novel pharmacologic mechanism unrelated to
      the parent toxophor was postulated. In an extensive literature survey, no further
      evidence was found for the reported high difference between the acute and the
      chronic dietary toxicity of imidacloprid and its plant metabolites to honeybees.
      The majority of data indicated a dietary no observed lethal-effect concentration
      >0.04 and 0.02 mg/L 50% sucrose solution, respectively, for an acute and a
      chronic dietary exposure of honeybees to either imidacloprid or its plant
      metabolites. Findings of chronic feeding studies with those plant metabolites
      where the toxophor had already been cleaved did not support the hypotheses of a
      novel pharmacologic mechanism unrelated to the parent toxophor. No increased
      treatment-related mortality or behavioral abnormalities were recorded in four
      independent research facilities during a 10-day dietary exposure of honeybees of
      different ages to sucrose solutions spiked with the respective metabolites at
      0.0001, 0.001, and 0.010 mg/L 50% sucrose solution.

PMID- 15499496
TI  - Comparative embryonic and larval developmental responses of estuarine shrimp
      (Palaemonetes pugio) to the juvenile hormone agonist fenoxycarb.
AB  - Grass shrimp (Palaemonetes pugio) were reared separately through both embryonic
      and total larval development during exposure to fenoxycarb at measured
      concentrations of <2.2 to 888 microg L(-1). A fenoxycarb concentration of 888
      microg L(-1) significantly (p < 0.05) inhibited embryonic development to larval
      hatching and extended the embryonic developmental period from 11.9 to 12.7 days.
      Exposure to fenoxycarb concentrations < or = 502 microg L(-1) had no significant
      (p > 0.05) effect on complete embryonic development. Significantly fewer shrimp
      successfully metamorphosed to postlarvae when exposed through complete larval
      development to fenoxycarb concentrations > or = 4 microg L(-1). Larval
      development of grass shrimp was therefore >2 orders of magnitude more sensitive
      to this juvenile hormone agonist than was embryonic development. Viability of
      larvae developing in fenoxycarb was concentration dependent. Development beyond
      third zoeal stage was significantly inhibited at fenoxycarb concentrations > or =
      190 microg L(-1), whereas development beyond fourth zoeal stage was inhibited by
      a concentration of > or = 45 microg L(-1). Fenoxycarb exposure of developing
      larvae did not alter either the duration of total larval development or the total
      number of larval stages before metamorphosis. Rearing of fenoxycarb-exposed
      embryos through larval development without further exposure had no significant
      effect on number of larval stages, larval development rate, or metamorphic
      success of larvae. Similarities in the sensitivity of grass shrimp larvae and
      mosquito larvae to fenoxycarb suggests that the use of a bioassay protocol
      measuring the metamorphic success of crustacean larvae would be a valuable
      adjunct to the hazard assessment of newly developed pesticides that target
      endocrine control of metamorphosis in insects and possibly other endocrine
      disrupting xenobiotics as well.

PMID- 15499498
TI  - Occurrence and distribution of pesticides in the province of Bologna, Italy,
      using honeybees as bioindicators.
AB  - Samples of honeybees (Apis mellifera, n = 92) from 14 beehive monitoring stations
      located in 3 townships in the province of Bologna were analyzed from April to
      October 2000. The concentration of 32 organophosphorus pesticides and 5
      carbamates was determined through liquid-liquid extraction followed by gas
      chromatography with a nitrogen-phosphorus detector and liquid chromatography
      coupled to mass spectrometry using atmospheric pressure chemical ionization in
      positive and negative ion modes. The most contaminated samples were from
      Granarolo Emilia where cereals (wheat, sorghum, and corn), sugar beets, and
      potatoes are the main agriculture products. Thirty-five pesticides were detected,
      with organophosphorus being the most abundant ones. Malathion was detected in 58%
      of the samples (mean level 0.360 mg/kg) followed by fenithrothion in 53% of the
      samples (mean level 0.544 mg/kg) and pirimiphos methyl in 48% of the samples
      (mean level 0.006 mg/kg). Temporal trends showed that the maximum detection
      frequency occurred in late spring and was associated with the use of treatment
      products and less rainfall. The obtained results demonstrated the feasibility of
      using honeybees for assessing pesticide exposure in agriculture settings.

PMID- 15499499
TI  - Uptake and effects on detoxication enzymes of cypermethrin in embryos and
      tadpoles of amphibians.
AB  - A number of factors have been suggested for recently observed amphibian
      decreases, and one potential factor is pesticide exposure. We studied the uptake
      and effects of environmentally relevant concentrations of the pyrethroid
      insecticide cypermethrin on two different amphibian species, Bombina variegata
      and Rana arvalis. The uptake from water of 14C-labeled cypermethrin (0.4
      microg/L) by eggs and tadpoles of B. variegata was investigated. After 24 hours
      of exposure, 153.9 ng cypermethrin/g fresh weight were found in embryos, thus
      indicating that the jelly mass of the eggs does not act as a sufficient physical
      barrier to protect embryos from exposure to this compound. Uptake of cypermethrin
      into tadpoles of both species and in all exposed individuals caused dose
      dependent deformities; behavioral abnormalities such as twisting, writhing, and
      coordinated swimming; and mortality. In tadpoles of B. variegata and R. arvalis,
      the activity of microsomal and cytosolic glutathione S-transferase (mGST and
      sGST, respectively) were measured after treatment with cypermethrin. Activities
      of both GST systems increased significantly with increasing duration and
      concentration of cypermethrin exposure, with the reaction seeming stronger in B.
      variegata than in R. arvalis tadpoles. Alpha-cypermethrin--a racemic mixture of
      two cis isomers of cypermethrin--induced a stronger enzymatic response in the
      cytosolic fraction of R. arvalis tadpoles than cypermethrin at the same
      concentration. The observed physical and behavioral abnormities caused by
      environmentally relevant concentrations of cypermethrin indicate that despite
      detoxication of the chemical via GST-system contamination of ponds by
      cypermethrin could result in adverse effects on the development of amphibian
      embryos and tadpoles.

PMID- 15499500
TI  - Toxicologic and histopathologic response of the terrestrial salamander Plethodon
      cinereus to soil exposures of 1,3,5-trinitrohexahydro-1,3,5-triazine.
AB  - Red-backed salamanders (Plethodon cinereus) were exposed to four different
      concentrations of 1,3,5-trinitrohexahydro-1,3,5-triazine (RDX) in soil under
      controlled laboratory conditions for 28 days. Wild-caught P. cinereus (N =
      20/treatment) were exposed to target concentrations of 5,000, 1000, 100, 10, and
      0 mg RDX/kg soil (dry wt) using a microcosm design. Animals were fed 5 to 10
      uncontaminated mutant Drosophila flies every 3 days and monitored daily. Animals
      were weighed 1 day before being placed in treatment and weekly thereafter. RDX
      concentrations in soil were analytically determined after the compound was added
      and mixed at the beginning, the midpoint, and the end of exposure. RDX soil
      concentrations were relatively stable throughout the exposure period. Signs of
      overt toxicity were observed primarily in the highest exposure group. Salamanders
      exposed to 5,000 mg RDX/kg soil exhibited signs of neuromuscular effects
      (lethargy, gaping, hypersensitivity, tremors) and exhibited significant weight
      loss. A single moribund animal from this group lost >20% of its original body
      weight and was killed. Animals in this exposure group also lost weight relative
      to animals in other treatments. Histopathologic evaluations, including an
      evaluation of melanomacrophage parameters, indicated no strong treatment-related
      findings. This study provided information regarding the effects from subchronic
      dermal exposure of a terrestrial amphibian species to RDX in soil and provides a
      microcosm approach to the evaluation of toxicity of contaminants in soil to a
      terrestrial vertebrate.

PMID- 15499501
TI  - Organ-specific toxicokinetics and dose-response of arsenic in tilapia Oreochromis
      mossambicus.
AB  - We appraised organ-specific toxicokinetics and dose responses of arsenic burdens
      in tilapia Oreochromis mossambicus. We kinetically linked an Area-under-the-curve
      (AUC)-based acute toxicity model and a pharmacodynamic model to derive dose
      response relationships between equilibrium organ-specific arsenic concentrations
      and mortality effects. The AUC-based acute toxicity model was also used to derive
      organ-specific internal effect concentration (IEC)-time-response relationships,
      which can also be applied to predict a time-mortality profile. We conducted a 7
      day exposure experiment to obtain toxicokinetic parameters, whereas the AUC-based
      acute toxicity model was verified with LC50(t) data obtained from a 7-day acute
      toxicity bioassay. Our results demonstrated that 96-hour LC50 and incipient LC50
      for tilapia exposed to arsenic are 28.68 (95% confidence interval to 24.92 to
      32.44) and 25.55 mg L(-1), respectively. Dose-response relationships followed the
      Hill equation, which could be expressed as organ-specific bioconcentration
      factors and incipient LC50. Organ-specific dose-response relationships showed
      that muscle, gill, and liver have a relatively steep sigmoid dose-response
      profile in that IEC50 were 26.6, 62.5, and 78.5 microg g(-1) dry wt (dw),
      respectively. Organ-specific arsenic internal lethal burdens were the highest in
      the gill and the lowest in the muscle in waterborne-exposed tilapia. The IEC and
      target-organ concentrations derived in this study can be used in site-specific
      risk assessment.

PMID- 15499502
TI  - Confirming the species-sensitivity distribution concept for endosulfan using
      laboratory, mesocosm, and field data.
AB  - In Australia, water-quality trigger values for toxicants are derived using
      protective concentration values based on species-sensitivity distribution (SSD)
      curves. SSD curves are generally derived from laboratory data with an emphasis on
      using local or site-specific data. In this study, Australian and non-Australian
      laboratory-species based SSD curves were compared and the concept of species
      protection confirmed by comparison of laboratory-based SSD curves with local
      mesocosm experiments and field monitoring data. Acute LC50 data for the
      organochlorine pesticide endosulfan were used for these comparisons; SSD curves
      were fitted using the Burr type III distribution. SSD curves indicated that the
      sensitivities of Australian fish and arthropods were not significantly different
      from those of corresponding non-Australian taxa. Arthropod taxa in the mesocosm
      were less sensitive than taxa in laboratory tests, which suggests that laboratory
      generated single-species data may be used to predict concentrations protective of
      semifield (mesocosm) systems. SSDs based on laboratory data were also protective
      of field populations.

PMID- 15499503
TI  - Influence of a mine tailing accident near Donana National Park (Spain) on heavy
      metals and arsenic accumulation in 14 species of waterfowl (1998 to 2000).
AB  - This article presents the impact on waterbirds in Donana National Park (Spain) of
      an accidental release of 5 million m3 acid waste produced by the processing of
      pyrite ore. Heavy metals (zinc, copper, cadmium, and lead) and arsenic were
      measured in several soft tissues (liver, kidney, and muscle) taken from 14
      waterfowl species collected between April 1998 and May 2000. The main source of
      copper and zinc found in the waterfowl species examined was the spill waste,
      whereas cadmium, lead, and arsenic could also came from other sources. Kidney was
      the primary organ for cadmium and lead accumulation, whereas liver accumulated
      the most zinc and copper. Arsenic was concentrated in both muscle and liver
      tissue. The degree of contamination of the area where the birds lived, their age,
      their sex their size, and the time since the spill were found to have less
      influence than species and trophic level on the accumulation of metal in organs
      and tissues. Four species (Anser anser, Ciconia ciconia, Larus ridibundus, and
      Porphyrio porphyrio) were found to have the highest levels of the 5 elements.

PMID- 15499504
TI  - Immune function and organochlorine pollutants in Arctic breeding glaucous gulls.
AB  - Organochlorine contaminants (OCs) are known to affect the immune systems of
      wildlife, and in this study we assessed the relationship between blood
      concentration of different OCs and measurements relevant to immune status and
      function in arctic breeding glaucous gulls (Larus hyperboreus). In 1997 and 2001,
      we counted white blood cells (heterophils and lymphocytes) from blood smears, and
      in 2000 and 2001 we injected two novel nonpathogenic antigens (diphtheria and
      tetanus toxoids) into the pectoral muscle of gulls and measured the primary
      antibody responses. We then related these measurements to the blood
      concentrations of three pesticides (hexachlorobenzene [HCB], oxychlordane, and
      p,p'-dichlorodiphenyldichloroethylene) and seven different polychlorinated
      biphenyl congeners (PCB 101, 99, 118, 153, 138, 180, and 170). There were
      significant or near significant positive relationships (0.1 > p > 0.001) between
      most persistent OCs and the levels of heterophils in the blood for both sexes in
      1997 and for male gulls in 2001. Similarly, levels of all persistent OCs and
      lymphocytes were positively related (0.1 > p > 0.001) in both sexes in 1997. This
      suggests that OCs are causing alterations to immune systems, which may decrease
      their efficiency and make the birds more susceptible to parasites and diseases.
      In female gulls, the antibody response to the diphtheria toxoid was significant
      and negative for HCB (p < 0.01) and weaker, but significant, for oxychlordane (p
      < 0.05), suggesting that OCs were causing an impairment of the humoral immunity.
      Various OCs have been linked to negative effects in our study population,
      including decreased survival and reproduction, and this study suggests that such
      compounds also affect immune status and function.

PMID- 15499505
TI  - Polybrominated diphenylethers and methoxylated tetrabromodiphenylethers in
      cetaceans from the Mediterranean Sea.
AB  - Eight tetrabrominated to hexabrominated diphenylethers were present at ppb levels
      in liver from cetaceans found stranded on the beaches of the Mediterranean Sea,
      Italy. The highest concentration was found in striped dolphin (sum polybrominated
      diphenyl ethers [PBDE] 8133 ng/g l.w.) and the lowest concentration in bottlenose
      dolphin (sum PBDE 66 ng/g lipid weight [l.w.]). The predominant congener in all
      samples was 2,2',4,4'-tetraBDE (PBDE # 47) followed by, in decreasing order, the
      pentaPBDE # 99 and 100 and the hexaPBDE # 154 and 153. In 12 of the 14 analyzed
      samples, 3 different methoxylated PBDEs (MeO-PBDE # 1, 2, and 3) were detected at
      semiquantitatively calculated concentration ranges of 2 to 14 ng/g l.w.; 5 to 167
      ng/g l.w.; and 7 to 628 ng/g l.w., respectively. In addition, several
      unidentified bromine compounds were seen when screening the samples in negative
      chemical ionization (NCI) mode monitoring m/z 79 and 81, which illustrates the
      importance of running both electron-impact ionization and NCI when analyzing
      environmental samples. Electron-impact ionization is more specific for monitoring
      the molecular ion compared with NCI, which might overestimate the concentration
      of certain PBDE congeners.

PMID- 15499506
TI  - Congener-specific polychlorinated biphenyls in cetaceans from Taiwan waters.
AB  - During 2000 to 2001, a total of 73 blubber samples from 13 species of stranded or
      accidentally captured cetaceans were collected from Taiwan coastal waters for
      polychlorinated biphenyl (PCB) analysis. After homogenization, saponification,
      liquid-liquid extraction, and silica-gel solid-phase extraction, PCB
      concentrations were determined by gas chromatography/mass spectrometry. Total
      concentrations of 19 PCB congeners (SigmaPCBs) were between 0.23 microg/g lipid
      weight of Risso's dolphin to 33.73 microg/g lipid weight of rough-toothed
      dolphin. Pentachlorobiphenyls, hexachlorobiphenyls and heptachlorobiphenyls were
      the predominant PCB congeners species. PCB153 was the most abundant congener in
      all samples. The PCB153/SigmaPCBs consistently comprised between 20% to 30% of
      all congeners. The toxicity measured as 2,3,7,8-tetrachlorodibenzo-p-dioxin
      equivalents (TEQs) were from 2.7 pg/g lipid weight of finless porpoise to 2,900
      pg/g lipid weight of rough-toothed dolphin. PCB 118, a mono-ortho congener, was
      the largest contributor to TEQs. PCB concentrations and TEQs were higher in
      mature male than in immature male animals but were inconsistent in female animals
      because of a possible transferring of PCBs from maternal cetaceans to their
      offsprings during gestation and lactation. Stranded cetaceans had significantly
      higher PCB levels than by-catch cetaceans because of their higher lipid
      consumption during starvation or illness. From the collected samples, we also
      found that cetaceans from Taiwan waters had relatively lower PCB concentrations
      and TEQs than those from high-latitude areas.

PMID- 15499507
TI  - Characterization of soils containing adipocere.
AB  - The formation of adipocere (commonly known as grave wax), a spontaneous
      inhibition of postmortem changes, has been extensively analyzed in forensic
      science. However, soils in which adipocere formation occurs have never been
      described in detail. Therefore, this study is intended as a first step in the
      characterization of soils containing adipocere. Two grave soils (Gleyic
      Anthrosols) that prevent the timely reuse of graves due to the occurrence of
      adipocere and a control soil (Gleyic Luvisol) were selected from a cemetery in
      the Central Black Forest (Southwest Germany). Descriptions of soil morphology and
      a wide assay of physical, chemical, and microbiologic soil characteristics were
      accomplished. In contrast to the control soil, the grave soils were characterized
      by lower bulk density and pH. The degradation of the soil structure caused by
      digging led to a higher water table and the expansion of the reducing conditions
      in the graves where the prevalent absence of oxygen in range of the coffins
      inhibited decomposition processes. Although the formation of adipocere led to the
      conservation of the buried corpses, phosphorus, dissolved organic carbon, and
      cadavarine leaching from the graves was observed. Microbial biomass and microbial
      activity were higher in the control soil and hence reflected the inert character
      of adipocere. The study results clearly show the need for additional approaches
      in forensic, pedologic, and microbiologic research.

PMID- 15499508
TI  - [Integrated delivery systems in California--success and failure determining
      factors for the first 10 years and impetus for Germany].
AB  - Since the coming into effect of the Health Care Modernization Act
      (Gesundheitsmodernisierungsgesetz) the conditions for integrated health care
      delivery are favourable in Germany. However, comprehensive approaches are a long
      time in coming. In contrast, integrated health care delivery as an integral part
      of the spreading of managed care entered a further stage of development, which
      enables health care decision makers to draw conclusions regarding the further
      development of integrated health care delivery in Germany. Based on case studies
      integrated delivery systems in the San Francisco Bay Area have been analyzed with
      the objective to evaluate pitfalls and successful strategies for integrated
      health care delivery. The major pitfalls refer to an insufficient local focus, a
      lack of actual integration and the application of per capita reimbursement (which
      is a key subject on the political agenda in Germany as well) within integrated
      delivery systems. On the contrary, successful strategies include achieving a
      dynamic tension between centralized and decentralized coordination, internal and
      external relationship management, well organised human resource management
      including a well-defined corporate policy and a comprehensive implementation of
      information technology. Based on US experiences with integrated delivery systems
      implications for the design of integrated health care delivery in Germany are
      discussed.

PMID- 15499509
TI  - [Effectiveness of an outpatient disease management programme for chronic heart
      insufficiency patients].
AB  - The effectivity of a disease management programme (DMP) for outpatients suffering
      from chronic heart insufficiency (CHI) in primary care is presented. The
      programme is predominantly based on a weekly telephone monitoring by a case
      manager using a standardised questionnaire that scores CHI-relevant information
      of the patient. If the score exceeds a predefined limit the patient's general
      practitioner is alarmed. An observational study including a total of 115 patients
      indicates a significant decline of the hospital admission rate (p < 0.0001), as
      the primary outcome measure, whereas the total length of hospitalization remained
      constant. The findings are compared with other studies' results and the aims of a
      randomised controlled trial on the efficacy of DMP on patients with chronic heart
      failure are discussed.

PMID- 15499510
TI  - [Notes on the GKV-modernization law (GMG)--a dentist's trend analysis].
AB  - Effective January 1st 2004 medical aid for patients receiving aid by means of the
      Federal German social welfare act has been transferred from the local social
      welfare offices to the statutory health insurances by decree regarding act
      modernisation of the statutory health insurance (GMG). The authors analyse the
      epidemiological and economical parameters concerning dental medical care for the
      city of Wuppertal on the basis of the experiences from 1994 to 2003 and attempt a
      well-founded forecast: the quality of medical standards will decline, whereas
      cost will rise.

PMID- 15499511
TI  - ["They'll never come back...""--Expectations and reality of occupational
      reintegration of teachers unfit for service].
AB  - AIM OF THE STUDY: The reactivation of teachers with experience of both life and
      the profession who have become unfit for work is regarded by politicians not only
      as a suitable measure against the imminent lack of teaching staff, but also as a
      promising strategy for reducing the cost of health care. The aim of our study was
      to gather new evidence- based information on the occupational reintegration of
      teachers who took early retirement and to investigate to what extent official
      medical reactivation examinations are an effective instrument of tertiary
      prevention. DATABASE AND METHODS: In a prospective total assessment (the entire
      state of Bavaria) over the period of 1997 - 1999 all official medical
      examinations in the public health centres (Gesundheitsamter und Medizinische
      Untersuchungsstellen der Bezirksregierungen) were evaluated with regard to the
      reactivation of teachers unfit for work. The analysis included e. g. socio
      demographic/occupational factors, the morbidity spectrum, rehabilitation and the
      assessment of performance. The answers given in a standardised, anonymous
      questionnaire provided the database. Evaluation was carried out by means of
      descriptive statistics. RESULTS: Of the 1465 teachers studied, 64 % (n = 939)
      were women and 36 % (n = 526) were men. The median age was 53 years (range: 31 -
      63 years), and the proportion of over 60-year-olds was 5.5 %. 22 % of those who
      took early retirement were recognised as being severely disabled. In 77 % of
      cases, examination of unfitness for work was carried out at the order of the
      authorities. 57 % (n = 835) of the teachers had taken part in at least one
      medical rehabilitation measure, 13 % (n = 190) in at least one occupational
      rehabilitation measure. Within the morbidity spectrum, psychic and psychosomatic
      illnesses (F-ICD10) took first place with a share of 59 % the prevalence in
      female teachers of such illnesses was significantly higher than that in male
      teachers (p < 0.05). Among the psychiatric diagnoses, depressive illnesses
      dominated (share: 35 %). The most frequent somatic diseases were
      muscular/skeletal disorders (M-ICD10) in 12 % of cases, then cardiovascular
      disorders (I-ICD10) in 7 % and malignant tumours (C-ICD 10) in 5 % of cases. In
      33 % of cases multi-morbidity was found. 93 % (n = 1,360) of the teachers
      investigated in follow-up examinations were again classified as unfit for work.
      In only 7 % (n = 105) reactivation was recommended by the physician; the lowest
      reactivation quotas were found among teachers with psychic illnesses and grammar
      school teachers. In who teachers that returned to work, compared to those still
      unfit for work, a lower age and lower prevalence of severe disability, multi
      morbidity and psychic disturbances were objectified. CONCLUSIONS: Teachers who
      take early retirement return to the profession only in exceptional cases. The
      time and expense needed for reactivation examinations should be critically
      compared with the benefits. The same applies to the quality of the results of
      intervention and rehabilitation measures for restoring psychological and physical
      health. In this context problem-oriented disability management appears
      superfluous.

PMID- 15499512
TI  - [In-house questioning on patient satisfaction in a maximum resource clinic-
      report from practice].
AB  - Since 1999, the statutory obligation of all German hospitals to establish an
      internal quality management system has resulted in an increase of patient surveys
      on inpatient care. Information on the subjective satisfaction of the patients is
      of particular interest because improvements may be realised. In the present
      paper, the objectives, the methodology and the choice of a tested survey
      instrument, the interpretation of the results and the practical problems in
      implementing a survey on patient satisfaction at the Leipzig University Hospital
      (a public institution comprising 1,464 beds in 2001) will be reported. This is
      intended to facilitate comparable projects in the future and to enable hospitals
      with fewer resources to organize and use such surveys. Altogether, 1,718
      questionnaires (Hamburg questionnaires on patient stay in hospital, HFK) from 43
      wards could be evaluated. The high satisfaction determined (mean values of the
      scores for 10 test parameters are between 1.72 and 2.02 on a 5-point scale)
      corresponds to the general tendency of patients to make socially desirable
      responses. Covert dissatisfaction was therefore analysed comparing the relative
      frequencies of complete and limited satisfaction at item level. Sociodemographic
      patient characteristics such as age and stay in hospital were of no substantial
      relevance. One important aim of the Leipzig survey project was to give detailed
      feedback within brief time periods. The project focussed on a differentiated and
      early monitoring of responses. If requested, an oral presentation of the results
      was made to each structural unit. This presentation included the spontaneous
      responses of the patient, which enhanced the acceptance of the investigation by
      the medical staff.

PMID- 15499513
TI  - [Surface disinfection in nursing homes--what is really happening? Study of
      control success in three Duisburg nursing homes].
AB  - The effectiveness of cleaning and disinfection of environmental surfaces was
      evaluated in three nursing homes using bacteriological monitoring. Samples from
      inmates (nose, throat and wounds) and surface cleaning equipment were also taken.
      Cleaning solutions, disinfectants and cleaning clothes were found to be highly
      contaminated in two of three institutions. Referring to the surfaces in some
      cases disinfection didn't reduce bacterial colony counts and seeded MRSA as a
      potential pathogen in one nursing home. Six MRSA-positive inmates and identical
      strains were registered in the environment. MRSA can be used as a marker organism
      to demonstrate effectiveness of cleaning. To achieve further improvement
      bacteriological monitoring can help in focussing special cleaning and
      disinfection related problems.

PMID- 15499514
TI  - [Interventions to prevent health risks due to tobacco smoke in pregnant women,
      postpartum women and their infants].
AB  - The aim of this study was to develop recommendations for interventions aiming at
      reducing health risks due to tobacco smoking in pregnant women, women postpartum
      and their infants. Meta-Analyses and selected studies are summed up.
      Epidemiological findings and health risks due to smoking are summed up.
      Subsequently findings from intervention studies are cross-referenced and
      integrated as recommendations. Interventions may be divided into three
      categories: 1. interventions to obtain abstinence in pregnancy, 2. interventions
      for relapse prevention after abstinence has been attained in pregnancy, 3.
      interventions aimed at reducing exposure to environmental tobacco smoke in homes
      with children. Empirical evidence is cross-referenced to the following points: 1.
      Self-help materials, 2. brief counselling, 3. more time-consuming counselling, 4.
      interventions to reduce exposure to environmental tobacco smoke and 5.
      interventions by midwives. Results from meta-analyses as well as results from
      selected studies suggest the following recommendations: 1. use of a trusting
      relationship in counselling, 2. repeated counselling, 3. complementary use of
      self-help materials; self-help material alone is not effective enough, 4. use of
      state-of-the-art counselling approaches and, 5. theoretical foundation and
      appropriate individualized counselling.

PMID- 15499515
TI  - [The readiness of women, after they have given birth to children, to participate
      in individualized counselling for smoking cessation ].
AB  - OBJECTIVES: Smoking after pregnancy implies health risks for both the woman and
      the newborn. Smoking cessation interventions postpartum can prevent relapse in
      women who quit during pregnancy, protect the infant from environmental tobacco
      smoke (ETS), and motivate smokers to quit. The readiness of women postpartum to
      participate in smoking cessation counselling is described. METHODS: In 6
      maternity wards n = 2790 women were screened for smoking, n = 1128 smoked before
      pregnancy. Of these n = 869 gave informed consent. Information on
      sociodemographic status and smoking behaviour is available for n = 642
      participating women and for n = 217 non-participating women. RESULTS: No
      differences between women participating and non-participating were found in age
      (p >.05) and having a partner (p >.05). Participants were slightly higher
      educated (p <.001) and were mainly in maintenance (44 %) or in precontemplation
      stage of change (38 %). The proportions were 44 % and 22 % in the group of the
      non-participating women. CONCLUSIONS: The readiness of women postpartum to
      participate in smoking cessation counselling was high. By reaching abstinent
      women and women not motivated to quit, a target group was addressed that barely
      benefits from currently existing preventive activities. Maternity wards are an
      effective location for addressing smoking behaviour of mothers.

PMID- 15499516
TI  - [Functional outcomes after penetrating keratoplasty in pseudoexfoliation syndrome
      (PEX)-keratopathy].
AB  - PURPOSE: Keratopathy in pseudoexfoliation syndrome (PEX-keratopathy) is a
      particular form of corneal endothelial decompensation, which requires a
      penetrating keratoplasty (PK) for visual rehabilitation at advanced states. The
      aim of this study was to evaluate the functional outcome and the development of
      intraocular pressure (IOP) after PK in patients with PEX-keratopathy depending on
      the presence of pre-existing glaucoma. PATIENTS AND METHODS: This retrospective
      study included 21 eyes of 21 patients (age 78.6 +/- 7.5 years) with a mean
      postoperative follow-up of 1.8 +/- 2.2 (median 2) years. The diagnosis of PEX
      keratopathy was confirmed clinically as well as by electron microscopy. The
      recipient and donor trephinations were performed from the epithelial side using
      an 193 nm excimer laser (n = 11) or mechanically (n = 10). An iridotomy was
      performed routinely during PK. The postoperative treatment with topical steroid
      was standardized. RESULTS: Preoperatively, a secondary open-angle glaucoma (SOAG)
      with optic nerve damage was diagnosed in 11 patients (52 %). Topical
      antiglaucomatous treatment was needed in 81 % of patients with SOAG. Six weeks
      postoperatively, patients with SOAG showed a higher prevalence of increased
      intraocular pressure (IOP) and/or antiglaucomatous treatment compared to patients
      without SOAG (45 % vs. 20 %). Most of the mild-early intraocular pressure
      elevations were controlled in both groups during the follow-up. From one year
      post-PK, there was an increased need for topical antiglaucomatous treatment in
      both patient groups. In all eyes the IOP was controlled by topical
      antiglaucomatous treatment. Preoperatively, visual acuity was comparable in
      patients with and without SOAG (0.06 +/- 0.09 vs. 0.08 +/- 0.1, p = 0.7), but
      increased significantly more in patients without SOAG (0.38 +/- 0.1, median 0.4)
      than in patients with SOAG (0.2 +/- 0.1, median 0.2; p = 0.01) after PK. Visual
      acuity remained stable in both groups throughout the follow-up period. During
      follow-up only one eye developed an episode of reversible endothelial graft
      rejection 18 months postoperatively. An irreversible graft failure was seen in
      none of the patients. CONCLUSION: The functional outcome after PK in PEX
      keratopathy seems to be strongly associated with pre-existing SOAG. Patients
      without SOAG may expect good visual rehabilitation without persistent
      postoperative IOP increases. However, patients should be followed-up for a
      prolonged period of time, because from 1 year following PK the need for topical
      antiglaucomatous treatment increased significantly.

PMID- 15499517
TI  - [A new therapy concept for the treatment of dry eye--the usefulness of
      phospholipid liposomes].
AB  - BACKGROUND: Most of the eye drops currently used replace only the aqueous phase
      of the tear film. But, due to the fact that, with approximately 80 % of the
      patients with a dry eye, a disturbance of the lipid phase is present, an approach
      for new treatment methods needed to be found. We examined a new therapy concept
      with an eye spray containing liposomes for the therapy of the "dry eye" in a long
      term study. GOAL: An examination of the effectiveness of a liposome eye spray
      (TEARS AGAIN, Optima Pharmaceutical GmbH, Germany) in patients with "dry eye"
      compared with a spray containing a balanced salt solution was carried out.
      METHODS: Between August 2003 and May 2004 a double-blind study with 382 patients
      was accomplished. The treatment group (V; n = 191) was compared with the control
      group (K; n = 191) for a period of 6 months regarding the following examination
      criteria: eyelid edge parallel conjunctival folds (LIPCOF), BREAK UP time (BUT),
      Schirmer I test, best corrected visual acuity, as well as slit lamp findings of
      the cornea and conjunctiva. Follow-up was after 4 weeks and 6 months. The
      statistical analysis was performed with the statistical program SPSS v.11.5.
      RESULTS: The examined parameters such as LIPCOF, BUT and Schirmer were
      significantly better in the treatment group than in the control group. We found
      likewise significant improvements of the inflammations of the edge of eyelid with
      a remarkable decrease of around 89.5 %. Questioning of the patients resulted in,
      among other things, the belief that the liposome eye spray led altogether to a
      clear subjective improvement of the symptoms in 72 % of the cases, although an
      initial burning sensation was mentioned after the application. All patients were
      of the opinion that application with a spray is more favourably and more pleasant
      than teardrops. CONCLUSION: The liposome tear substitute shows statistically
      significant advantages against a balanced salt solution. This new liposome eye
      spray represents a new, revolutionary and effective procedure in the therapy of
      the "dry eye". Considering the disturbance of the lipid phase in 80 % of the
      patients, TEARS AGAIN ought to be a first choice treatment.

PMID- 15499518
TI  - [Comparison of the optical coherence method (Zeiss IOL-Master) with two
      ultrasonographic biometric methods for the calculation of posterior chamber
      intraocular lenses after phacoemulsification as part of clinical routine].
AB  - BACKGROUND: The aim of this work was to investigate the accuracy of prediction of
      three different biometric methods for the calculation of posterior chamber
      intraocular lenses. METHODS: In 59 consecutive patients who underwent
      extracapsular cataract-extraction with posterior chamber intraocular lens
      implantation, we compared the refractive results at the first day (D1) and 6
      weeks (W6) after surgery with the calculated refraction of three biometric
      methods: the Carl Zeiss "IOL-Master 99" (IOLM), the Biovision "Echograph Class 1 
      Type B" (BIOV) and the Allergan Humphrey "Ultrasonic Biometer Mod. 820" (AHUB).
      For statistical calculation box-plots, the Wilcoxon signed-rank test and linear
      regression analysis were used. RESULTS: In all patients the mean of the
      postoperative refraction was - 0.07 D (SD: 1.41) at day 1 and 0.12 D (SD: 1.18)
      at week 6. Compared to the postoperative refraction at week 6, the calculated
      refractive values were higher in all three measuring devices: IOLM: + 0.28 D (SD:
      0.67), BIOV: + 0.60 D (SD: 0.88), AHUB: + 0.26 D (SD: 0.92). There were no
      statistically significant differences between IOLM and BIOV, or respectively,
      AHUB and BIOV (p < 0.0001), but a significant difference was found between IOLM
      and AHUB, (p = 0.906). To adjust for systematic differences of the agreement, one
      can calculate the postoperative refraction at week 6 (REF6) from IOLM by using
      the linear regression formula: REF6 = 1.1 x IOLM + 0.3. CONCLUSION: A comparison
      between the three biometric methods and the refractive results at day 1 and week
      6 after cataract surgery with implantation of a posterior chamber intraocular
      lens showed that the calculated mean values obtained from the three biometric
      methods are higher than the real postoperative refraction. Calculations using the
      Zeiss IOL-Master and the Allergan Humphrey Ultrasonic Biometer are closer to the
      patient's postoperative refraction than calculations using the Biovision
      Echograph.

PMID- 15499519
TI  - [Comparison of different methods for pupillometry for mesopic and scotopic
      conditions].
AB  - BACKGROUND: The aim of the study was to compare different methods for
      pupillometry, namely the Goldmann perimeter (gp), the Colvard pupillometer (cp)
      and the Procyon Video pupillometer (pvp). For the pvp three different
      illuminations were available: mesopic high, mesopic low, and scotopic. PATIENTS:
      The size of the pupil was measured in 100 eyes (50 healthy subjects) with the
      three different methods. We examined 29 females (58 %) and 21 males (42 %) with
      an average age of 25.16 years, ranging from 18 to 30 years. RESULTS: For the
      Goldmann perimeter, a mean pupil diameter of 4.39 mm +/- 0.62 mm was found under
      mesopic conditions (1.40 lux). For the Colvard pupillometer for scotopic
      conditions (0 lux), a mean pupil diameter of 6.80 mm +/- 0.81 mm was found. For
      pvp the pupil diameter ranged from 7.06 mm +/- 0.71 mm for scotopic (0.04 lux),
      over 6.24 mm +/- 0.80 mm for mesopic low (0.40 lux) to 4.65 mm +/- 0.73 mm for
      mesopic high conditions (4.00 lux). CONCLUSION: The comparison of the results
      showed a high correlation between the Goldmann perimeter and the Procyon Video
      Pupillometer for mesopic high with a minimum difference of 0.25 +/- 0.69 mm. By
      addition of 2.67 mm to the mesopic measurement of the Goldmann perimeter, the
      results for the Procyon Video pupillometer at the scotopic level, by addition of
      2.4 mm the scotopic measurement of the Colvard pupillometer could be achieved.

PMID- 15499520
TI  - [Clinical and molecular genetic findings in isolated sporadic Duane syndrome].
AB  - BACKGROUND: Duane retraction syndrome (DURS) accounts for 1 - 4 % of all cases of
      strabismus. Approximately 90 % of the cases are sporadic with a preponderance for
      females and the left eye. Many associated ocular and systemic findings have been
      described. Recently, mutations of SALL4 have been found in patients with
      autosomal-dominantly inherited Okihiro syndrome (DURS associated with forearm
      malformations). The aim of this study was the clinical examination of patients
      with isolated sporadic DURS and the molecular genetic analysis of SALL4 in these
      patients. SUBJECTS AND METHODS: Twenty-five patients with non-familial DURS (aged
      1 - 75 years, 16 female, 9male) were examined clinically and were interviewed
      concerning associated pathologies. DNA was prepared from peripheral lymphocytes,
      and the complete coding region of SALL4 was sequenced. RESULTS: In 18 patients
      DURS affected the left eye, in four the right eye, and was bilateral in three
      patients. One patient had fused vertebrae, one had a cone-rod-dystrophy. No
      hearing impairments or malformation of the upper limbs were observed. No mutation
      in the coding region of SALL4 could be detected. DISCUSSION: Associated
      conditions in DURS patients most commonly involve the ear, the spinal column, the
      kidneys and the heart and the upper limbs. No mutations in SALL4 could be
      detected in patients with isolated sporadic DURS as opposed to findings in
      familial Okihiro syndrome. However, Okihiro syndrome shows marked intra- and
      interfamilial variability, suggesting that in rare cases of isolated DURS a
      causative SALL4 mutation may be found.

PMID- 15499521
TI  - [Vergence dynamics and variability of fixation disparity in school children with
      reading-spelling disorders].
AB  - BACKGROUND: New computer-controlled psychophysical procedures allow one to
      measure some temporal aspects of binocular coordination. The present study
      investigates whether these procedures can be operated by children and whether the
      tests are useful to detect previously reported impairments in dynamics and
      stability of vergence in children with disability in reading and writing.
      METHODS: To assess the variability in vergence accuracy (fixation disparity), a
      stationary fusion stimulus appeared on a computer monitor superimposed by short
      term presentations of two dichoptic vertical nonius lines with varying horizontal
      offset. From the variability of the responses, a measure of vergence variability
      was deduced. Vergence velocity was estimated with nonius lines that appeared at a
      fixed delay of 400 ms after a sudden change in disparity of 30 minutes of arc.
      The full sample comprised 66 children, aged 7-16 years. 16 of these were not able
      to localize the nonius lines accurately in a control condition; therefore, these
      children were excluded from the following analysis. RESULTS: In the remaining 50
      children, a group of 30 pupils with different aspects of disability in reading
      and writing had a nearly significant worse vergence performance both with respect
      to convergence velocity and to variability of fixation disparity (as compared to
      a control group of n = 20). These two findings corresponded to each other since
      convergence velocity and variability of fixation disparity were correlated.
      CONCLUSIONS: The results confirm previous reports and suggest further research on
      temporal aspects of vergence with respect to dyslexia. The computer-controlled
      test procedures are applicable in children of about 10 years or older.

PMID- 15499522
TI  - [Factor VIII activity in patients with central retinal vein occlusion in
      comparison to patients with a history of pelvic and lower limb venous thrombosis
      and a healthy control group].
AB  - BACKGROUND: High factor VIII activity levels increase the risk of venous
      thromboembolism. This study was carried out to investigate the association
      between factor VIII activity and central retinal vein occlusion (CRVO) in
      comparison to patients with a history of venous thrombosis and a healthy control
      group. PATIENTS AND METHODS: We examined the factor VIII activity in 62 patients
      with CRVO, 67 patients with venous thrombosis and 107 healthy individuals. The
      study measure employed for factor VIII activity was a one-stage clotting assay.
      RESULTS: 53.2 % of the patients with CRVO had an elevated factor VIII activity of
      more than 150 % (> 150 IU/dl). 78.5 % of the patients with venous thrombosis and
      19.7 % of the healthy control group had an elevated factor VIII activity (> 150
      IU/dl). CONCLUSIONS: Elevated factor VIII activity is likely to have an influence
      on the pathogenesis of the central retinal vein occlusion.

PMID- 15499523
TI  - [Defect closure with scleral grafts].
AB  - BACKGROUND: Excessively draining fistulas may lead to enucleation when primary
      suture closure is not effective. In these cases preserved cadaver tissues such as
      sclera, fascia lata, dura mater and peritoneum have been used for patch graft
      repair with variable results. In this study, the clinical outcomes after
      transplantation of scleral patch grafts have been investigated. METHOD: Twenty
      eight eyes of twenty-seven patients underwent surgery with homologous scleral
      patch grafts for repair of excessively draining scleral fistulas after cataract
      surgery (n = 2), leaking filtering blebs following full-thickness filtration
      surgery (n = 7), large scleral perforations due to trauma (n = 7), corneo-scleral
      ulcerations due to severe eye burns (n = 9) or after radiotherapy of malignant
      melanoma (n = 3). The mean size of the rectangular grafts was 8.6 x 6.7 mm (+/-
      2.8/3.1 mm). Clinical follow-up was up to 73 months (median 30 months). RESULTS:
      Twenty-three of 28 eyes (82.1 %) showed functional closure after initial surgery
      without any wound complication such as patch retraction or leakage and without
      evidence of inflammation. In five eyes surgical revision was necessary. Two of
      these eyes had to be enucleated due to uncontrollable dehiscence after the second
      operation. Two eyes were enucleated at the patient's demand due to pain. The
      fifth eye showed effective closure after the second operation. CONCLUSION: In our
      study scleral patch grafts were useful in adequately closing large corneo-scleral
      defects in 24 of 28 eyes (85.7 %). The antigen load and, therefore, the rejection
      of the scleral grafts is minimized due to the denaturation of proteins during the
      alcohol treatment before storage.

PMID- 15499524
TI  - [Epibulbar dermoids--clinical features and therapeutic methods].
AB  - BACKGROUND: In a strict sense epibulbar dermoids are defined as congenital
      changes of mesodermal and ectodermal origin. Usually they are located at the
      limbus of the cornea in the inferotemporal quadrant, they can only rarely be
      observed in more central regions of the cornea. Intraocular structures are rarely
      involved. Connections to Goldenhar's oculo-auriculo-syndrome exist. Because of
      cosmetic reasons or a considerable astigmatism holding the danger of amblyopia a
      resection might be necessary. PATIENTS AND METHODS: Six patients (three girls and
      three boys) aged from 9 months to 6 years with limbal dermoids were included in
      the present study. All patients had been referred to the University Eye Hospital
      of Dresden for a possible therapy. RESULTS: All children showed a unilateral
      dermoid in the inferotemporal quadrant. In five cases the left eye was affected.
      In two patients a Goldenhar syndrome was present. In two patients a local
      resection of the dermoid was indicated. In three patients a keratoplasty (two
      lamellar, one penetrating) was additionally carried out. In the case of a two
      year-old girl only prophylactic treatment of amblyopia was considered. The
      postoperative results reached from uncomplicated healing (visual acuity 1.0) to
      full cloudiness of the transplant and re-keratoplasty (visual acuity lux).
      CONCLUSION: Controls of the dermoid in half-year intervals and surgical
      intervention in early childhood are recommended. Simple local resection or a
      combination with lamellar or penetrating (sclero)-keratoplasty are used. A
      penetrating keratoplasty is seldom necessary due to deep and central dermoids.
      The prognosis can be described as favourable.

PMID- 15499525
TI  - Epidemiological and genetic correlates of incident Chlamydia trachomatis
      infection in North American adolescents.
AB  - Epidemiological and genetic correlates of Chlamydia trachomatis infection were
      examined prospectively in 124 male and 361 female adolescents at high risk for
      human immunodeficiency virus type 1 (HIV-1) infection. Seventy percent of
      subjects were African American, and 68% had HIV-1 infection. As expected, younger
      age (<17 years), multiple sex partners (> or =2), and prior chlamydial infection
      predicted chlamydial infection during a 6-56-month follow-up period (P=.02,
      P=.02, and P=.03, respectively). Human leukocyte antigen (HLA) class II variant
      DQB1*06 (mostly *0602 and *0603) was associated with chlamydial infection (49%
      vs. 34%; adjusted relative odds [RO], 1.8; P=.005), as was HLA class I haplotype
      B*44-Cw*04 (10% vs. 4%; RO, 3.2; P=.009). DQB1*06 was found in 9 (75%) of 12
      female adolescents with chlamydial pelvic inflammatory disease. In contrast, sex,
      ethnicity, and HIV-1 infection did not predict chlamydial infection. These
      findings suggest that antigen presentation in adaptive immune responses may serve
      as a major factor in effective control of C. trachomatis infection. The
      underlying mechanisms remain to be experimentally elucidated.

PMID- 15499526
TI  - Community-adapted methicillin-resistant Staphylococcus aureus (MRSA): population
      dynamics of an expanding community reservoir of MRSA.
AB  - To define methicillin-resistant Staphylococcus aureus (MRSA) reservoirs in the
      community and their population dynamics, we studied the molecular epidemiology of
      a random sample (n=490) from a collection of 2154 inpatient and outpatient MRSA
      isolates during a 7-year period in San Francisco. We noted a progressive
      replacement of type II staphylococcal chromosomal cassette (SCC)mec-bearing
      isolates with type IV SCCmec-bearing isolates, which coincided with >4-fold
      increase in methicillin resistance between 1998 and 2002. Type IV SCCmec-bearing
      isolates involved in the increase in methicillin resistance belonged to 4
      molecular genotypes. These 4 genotypes were associated predominantly with
      community-onset disease, rather than hospital- or long-term-care facility-onset
      disease (76.9% vs. 19.4% vs. 3.7%; P=.0005), suggesting that they are not feral
      descendants of hospital isolates. The longitudinal results linked the dramatic
      increase in MRSA infections to an expanding community reservoir of MRSA genotypes
      with intrinsic community survival advantage.

PMID- 15499527
TI  - Virulence characteristics and phylogenetic background of multidrug-resistant and
      antimicrobial-susceptible clinical isolates of Escherichia coli from across the
      United States, 2000-2001.
AB  - BACKGROUND: Increases in antimicrobial resistance in Escherichia coli have been
      paralleled by an increasing incidence of E. coli sepsis, suggesting a possible
      link between resistance and virulence. METHODS: All 76 multidrug-resistant (MDR)
      E. coli isolates (i.e., those resistant to > or =3 antimicrobial agents,
      including ampicillin, ceftazidime, trimethoprim-sulfamethoxazole, gentamicin, and
      ciprofloxacin) reported to the Tracking Resistance in the United States Today
      studies during 2000-2001 and 76 closely matched pansusceptible control isolates
      were studied. Extended virulence profiles and E. coli phylogenetic group (A, B1,
      B2, or D) were compared between groups. RESULTS: The MDR isolates, which
      represented predominantly non-B2 phylogenetic groups (91%), exhibited
      significantly reduced molecular virulence, compared with the predominantly group
      B2-derived control isolates (58%). Only 30% of MDR isolates, compared with 61% of
      control isolates (P<.001), qualified as extraintestinal pathogenic E. coli
      (ExPEC), and even these isolates exhibited significantly lower virulence scores
      than did susceptible ExPEC (7.25 vs. 9.0; P=.001). Phylogenetic differences
      accounted for the apparent virulence differences between MDR and control
      isolates. CONCLUSIONS: These findings argue against a direct link between
      virulence traits and antimicrobial resistance in E. coli. Instead, they call into
      question why non-B2 strains are more commonly MDR, with differential exposure to
      selection pressure (including in agriculture) as one possible explanation.

PMID- 15499528
TI  - Deletion in the Shigella enterotoxin genes further attenuates Shigella flexneri
      2a bearing guanine auxotrophy in a phase 1 trial of CVD 1204 and CVD 1208.
AB  - BACKGROUND: We created a live, attenuated, oral Shigella vaccine by constructing
      a lineage of guanine auxotrophs and conducted a double-blind, placebo-controlled
      trial to ascertain (1) the attenuation profile of Delta guaBA Shigella flexneri
      2a, which harbors deletions in the guanine nucleotide synthesis pathway (CVD
      1204); (2) additional attenuation conferred by deletions in set and sen genes
      encoding Shigella enterotoxins (ShETs) 1 and 2, respectively (CVD 1208); and (3)
      the relative immunogenicity of these constructs. METHODS: Inpatient volunteers
      received a single oral dose of CVD 1204, CVD 1208 (10(7), 10(8), or 10(9) cfu),
      or placebo. Clinical, immunologic, and microbiologic responses were evaluated.
      RESULTS: Reactogenicity occurred in 8 of 23 recipients of CVD 1204, characterized
      by diarrhea (30%), fever (22%), and/or dysentery (17%), but in only 1 (5%) of 21
      recipients of CVD 1208 (brief fever) (P=.02, Fisher's exact test).
      Antilipopolysaccharide responses, as measured by antibody-secreting cell, serum,
      or fecal antibody levels, occurred in 67%, 71%, and 100% of recipients of CVD
      1204 and in 86%, 43%, and 100% of recipients of CVD 1208 at doses of 10(7),
      10(8), and 10(9) cfu, respectively. CONCLUSIONS: We conclude that 1 or both ShETs
      are virulence determinants in humans; their inactivation, in combination with
      Delta guaBA, leads to a well-tolerated and immunogenic Shigella vaccine
      candidate.

PMID- 15499529
TI  - Interleukin (IL)-12 and IL-23 are key cytokines for immunity against Salmonella
      in humans.
AB  - Patients with inherited deficiency of the interleukin (IL)-12/IL-23-interferon
      (IFN)- gamma axis show increased susceptibility to invasive disease caused by the
      intramacrophage pathogens salmonellae and mycobacteria. We analyzed data on 154
      patients with such deficiency. Significantly more patients with IL-12/IL-23
      component deficiency had a history of salmonella disease than did those with IFN-
      gamma -component deficiency. Salmonella disease was typically severe,
      extraintestinal, and caused by nontyphoidal serovars. These findings strongly
      suggest that IL-12/IL-23 is a key cytokine for immunity against salmonella in
      humans and that IL-12/IL-23 mediates this protective effect partly through IFN-
      gamma -independent pathways. Investigation of the IL-12/IL-23-IFN- gamma axis
      should be considered in patients with invasive salmonella disease.

PMID- 15499530
TI  - Colostrum obtained from women vaccinated with pneumococcal vaccine during
      pregnancy inhibits epithelial adhesion of Streptococcus pneumoniae.
AB  - Prevention of nasopharyngeal colonization may reduce the burden of pneumococcal
      infection during infancy. Colostrum obtained from Gambian mothers who had been
      vaccinated with either Pneumovax II or Mengivax A&C (n=8 per group) during
      pregnancy was examined for inhibition of adherence of Streptococcus pneumoniae
      serotypes 6B and 14 to pharyngeal epithelial cells in vitro. Pneumococcal
      adherence was significantly reduced in the presence of breast milk (P< or =.0001
      for S. pneumoniae serotype 14; P=.036 for serotype 6B), independent of the
      concentration of secretory IgA antibodies. Maternal vaccination with polyvalent
      pneumococcal polysaccharide vaccine boosts the capacity of colostrum to inhibit
      adherence of pneumococci to pharyngeal epithelial cells. In breast-feeding
      populations, maternal vaccination might prevent pneumococcal disease in young
      infants.

PMID- 15499531
TI  - Azithromycin modulates murine immune responses to pneumococcal conjugate vaccine
      and inhibits nasal clearance of bacteria.
AB  - Macrolide antibiotics, including azithromycin, have been implicated in the
      modulation of host immune responses, independently of their antimicrobial
      properties. The present work was designed to study the effect that azithromycin
      has on protective humoral immune responses induced by a 7-valent, polysaccharide,
      pneumococcal conjugate vaccine (PCV7). By use of a murine vaccination/challenge
      model, it was found that inoculation with azithromycin led to significantly lower
      primary antibody responses, decreased recall proliferative responses, and, in
      nasal cavities, impaired clearance of Streptococcus pneumoniae serotype 14 from
      the nasal cavities. The results demonstrate that azithromycin can be inhibitory
      with regard to protective immune responsiveness.

PMID- 15499532
TI  - Link between impaired maturation of phagosomes and defective Coxiella burnetii
      killing in patients with chronic Q fever.
AB  - Q fever is caused by Coxiella burnetii, a bacterium that survives in
      monocytes/macrophages by resisting their natural microbicidal activity. Because
      the link between bacterial killing and phagosome maturation has yet to be
      demonstrated, we evaluated responses in monocytes from both immunologically naive
      control subjects and patients with various manifestations of Q fever. Monocytes
      from patients with chronic Q fever in evolution, who do not control the
      infection, exhibited defective phagosome maturation and impaired C. burnetii
      killing. Both responses were stimulated in patients recovering from Q fever.
      Phagosome maturation and C. burnetii killing were significantly correlated.
      Defective phagosome maturation and impaired C. burnetii killing were induced by
      adding interleukin (IL)-10 to monocytes from convalescent patients and were
      restored by IL-10 neutralization in chronic Q fever in evolution. We show that
      phagosome maturation and microbial killing are linked in Q fever and that IL-10
      regulates both features of microbicidal activity.

PMID- 15499533
TI  - Randomized, controlled dose-optimization studies of dihydroartemisinin
      piperaquine for the treatment of uncomplicated multidrug-resistant falciparum
      malaria in Thailand.
AB  - BACKGROUND: Dihydroartemisinin-piperaquine (DP) is a new and relatively
      inexpensive artemisinin-containing fixed-combination antimalarial treatment. An
      adult treatment course contained 6.4 mg/kg dihydroartemisinin (DHA), which is
      >40% lower than the level in most artemisinin-containing combinations. This
      raised the possibility that the efficacy of the current coformulation may not be
      optimal in the treatment of multidrug-resistant falciparum malaria. METHODS: In 2
      large randomized, controlled studies in Thailand, the recommended dose of DP was
      compared with a regimen with additional artemisinin derivative (12 mg/kg; DP+)
      and with mefloquine plus artesunate (MAS3). RESULTS: A total of 731 patients were
      included: 201 in a hospital-based study and 530 in a community study. Day-28 cure
      rates in the hospital-based study were 100% (95% confidence interval [CI], 93.9%
      100%) in the MAS3 and DP+ groups and 98.3% (95% CI, 91%-99.7%) in the DP group,
      with a single recrudescence on day 21. In the community study, polymerase chain
      reaction genotyping-adjusted cure rates on day 63 were 96.1% (95% CI, 92.6%
      99.7%) in the DP group, 98.3% (95% CI, 96.1%-100%) in the DP+ group, and 94.9%
      (95% CI, 91.2%-98.6%) in the MAS3 group (P=.2). Adverse events were few, with an
      excess of mild abdominal pain in the DP group. CONCLUSIONS: The current dosage of
      DP (6.4 mg/kg DHA and 51.2 mg/kg piperaquine phosphate) given over the course of
      48 h is highly effective, safe, and well tolerated for the treatment of multidrug
      resistant falciparum malaria, and its efficacy is not improved by the addition of
      more DHA.

PMID- 15499534
TI  - Rare, highly pyrimethamine-resistant alleles of the Plasmodium falciparum
      dihydrofolate reductase gene from 5 African sites.
AB  - In eastern and southern Africa, there has been a rapid increase in the prevalence
      of alleles with mutations in the Plasmodium falciparum dihydrofolate reductase
      gene (dhfr) associated with increased risk of clinical failure of sulfadoxine
      pyrimethamine (S/P). Molecular methods for surveillance of these mutations are
      now widespread, but the usual analysis detects only the most prevalent allele in
      a polyclonal sample. We used a yeast-expression system to identify rare, highly
      pyrimethamine-resistant alleles of dhfr in isolates from 5 African countries-
      Kenya, Tanzania, Malawi, Gabon, and Nigeria. Only the isolates from Nigeria
      yielded significant numbers of novel resistant alleles, and only 1 of the alleles
      from any location showed a >3-fold increase in resistance to S/P or to
      chlorproguanil-dapsone. Overall, these results suggest that dhfr alleles that
      confer high levels of resistance to antifolates are rare, even in eastern and
      southern Africa, where pyrimethamine has been intensively used.

PMID- 15499535
TI  - Antimony plus recombinant human granulocyte-macrophage colony-stimulating factor
      applied topically in low doses enhances healing of cutaneous Leishmaniasis
      ulcers: a randomized, double-blind, placebo-controlled study.
AB  - Cutaneous leishmaniasis (CL) requires 2-6 months to heal. In an effort to reduce
      this healing time, we studied topically applied granulocyte-macrophage colony
      stimulating factor (GM-CSF) as an adjunct to antimonial therapy. Ten patients
      received antimony plus topical GM-CSF, and 10 patients received antimony plus
      placebo (saline). GM-CSF was diluted for topical use and was applied 3 times
      weekly for 3 weeks (1-2 microg/cm2/lesion). The mean +/- SD healing time was 43
      +/- 14 days in the GM-CSF group and was 104+/-79 days in the placebo group
      (P=.043). Ten (100%) of 10 patients in the GM-CSF group healed within 60 days,
      compared with 5 (50%) of 10 patients in the placebo group. Two of the patients in
      the placebo group required retreatment with antimony. In conclusion, topically
      applied GM-CSF is effective in the management of CL.

PMID- 15499536
TI  - Impaired T helper 2 response to aeroallergen in helminth-infected patients with
      asthma.
AB  - Helminthic infections have been shown to inhibit allergy skin-prick tests and to
      modify the course of asthma. We evaluated Dermatophagoides pteronyssinus-specific
      immune responses in patients with asthma by measuring levels of T helper 2 (Th2)
      cytokines in peripheral blood mononuclear cell (PBMC) cultures. PBMCs from
      Schistosoma mansoni-infected patients with asthma living in an area of
      polyhelminthic endemicity produced lower levels of interleukin (IL)-5 and IL-4 in
      response to D. pteronyssinus antigen (Ag) 1 than did PBMCs from helminth-free
      patients with asthma. In contrast, D. pteronyssinus Ag 1-specific production of
      IL-10 was higher in helminth-infected patients than in helminth-free patients.
      The addition of recombinant human IL-10 to D. pteronyssinus Ag 1-stimulated
      cultures of PBMCs from helminth-free patients led to down-modulation of
      production of IL-5. After helminth-infected patients with asthma received
      antihelminthic treatment, there was down-modulation of D. pteronyssinus Ag 1
      specific production of IL-10 in vitro. S. mansoni-infected patients with asthma
      produce lower levels of Th2 cytokines than do helminth-free patients with asthma,
      and this modulation is likely done by IL-10.

PMID- 15499537
TI  - T helper cell type 2 responsiveness predicts future susceptibility to
      gastrointestinal nematodes in humans.
AB  - Some humans are persistently more susceptible to gastrointestinal nematodes than
      others. Here, for the first time, susceptibility to reinfection has been linked
      to host cytokine responses. Ascaris lumbricoides and Trichuris trichiura
      abundance was assessed immediately before and 8-9 months after deworming in a
      Cameroonian population (starting n=191). Profiles of whole-blood cytokine
      responses to parasite antigens (for interleukin [IL]-5, IL-13, IL-10, IL-12p40,
      tumor necrosis factor- alpha , and interferon- gamma), assayed before treatment,
      were significantly related both to an overall measure of host susceptibility and
      to susceptibility to reinfection. Significant effects were primarily due to a
      negative association between IL-13 and IL-5 responses and infection. Persistently
      susceptible individuals were, therefore, characterized by a weak T helper cell
      type 2 response. The apparent plasticity of age-specific cytokine response-worm
      abundance relationships between different populations is also discussed.

PMID- 15499538
TI  - Recombinant Ascaris 16-Kilodalton protein-induced protection against Ascaris suum
      larval migration after intranasal vaccination in pigs.
AB  - We recently cloned a protective antigen that is commonly expressed in Ascaris
      species that infect humans and pigs. We evaluated the vaccinal effects of this 16
      kilodalton protein (As16) in pigs, the natural host of Ascaris suum, by
      intranasal immunization. Pigs that received Escherichia coli-expressed
      recombinant As16 (rAs16) coupled with cholera toxin (CT) had significantly
      elevated levels of rAs16-specific serum immunoglobulin G (IgG) and mucosal
      associated IgA antibodies. rAs16 evoked a type II immune response characterized
      by elevated levels of interleukin-4 and -10 in the culture supernatants of
      peripheral blood mononuclear cells of the vaccinated pigs. An increased level of
      rAs16-specific serum IgG1 was also detected. Pigs vaccinated with rAs16-CT were
      protected from migration of A. suum larvae through the lungs, as indicated by a
      58% reduction in the recovery of lung-stage third-stage larvae (L3), compared
      with that in nonvaccinated controls. Purified immunoglobulin from rAs16-CT
      vaccinated pigs inhibited survival of infective L3 and interrupted the molting of
      lung-stage L3. Immunofluorescence studies revealed that this immunoglobulin bound
      to the digestive tracts of L3, suggesting that it might inactivate functions of
      the gut tissues of Ascaris species. We conclude that rAs16 is a promising mucosal
      vaccine candidate for pig and human ascariasis.

PMID- 15499539
TI  - Activation of the cytokine network and unfavorable outcome in patients with
      yellow fever.
AB  - To study the contribution of inflammatory mediators to the pathogenesis of yellow
      fever (YF), the serum levels of several cytokines and chemokines were measured in
      7 patients with fatal YF (f-YF), 11 patients with nonfatal hemorrhagic YF (nf/h
      YF), and 18 patients with nonfatal nonhemorrhagic YF (nf/nh-YF). The levels of
      interleukin (IL)-6, monocyte chemoattractant protein-1, interferon-inducible
      protein (IP)-10, tumor necrosis factor- alpha , and IL-1 receptor antagonist (IL
      1RA) were all statistically significantly higher in the patients with f-YF than
      in those with nf/nh-YF. In patients with nf/h-YF, only levels of IP-10 and IL-1RA
      were significantly elevated. The high levels of pro- and anti-inflammatory
      cytokines and chemokines in serum from patients with f-YF are reminiscent of
      those seen in patients with bacterial sepsis. This finding has implications for
      the understanding of the pathophysiology of YF and the development of therapeutic
      strategies.

PMID- 15499540
TI  - Respiratory syncytial virus epidemiology in a birth cohort from Kilifi district,
      Kenya: infection during the first year of life.
AB  - We report estimates of incidence of respiratory syncytial virus (RSV) infection
      during the first year of life for a birth cohort from rural, coastal Kenya. A
      total of 338 recruits born between 21 January 2002 and 30 May 2002 were monitored
      for symptoms of respiratory infection by home visits and hospital referrals.
      Nasal washings were screened by use of immunofluorescence. From 311 child-years
      of observation (cyo), 133 RSV infections were found, of which 48 were lower
      respiratory tract infections (LRTIs) and 31 were severe LRTIs, resulting in 4
      hospital admissions. There were 121 primary RSV infections (248 cyo), of which 45
      were LRTIs and 30 were severe LRTIs, resulting in 4 hospital admissions; there
      was no association with age. RSV contributed significantly to total LRTI disease
      in this vaccine-target group.

PMID- 15499541
TI  - Human monkeypox infection: a family cluster in the midwestern United States.
AB  - BACKGROUND: The outbreak of monkeypox in the Midwestern United States during June
      2003 marks the first documented human infection in the Western Hemisphere.
      Consistent with those in outbreaks in Africa, most cases in this outbreak were
      associated with febrile rash illness. We describe a cluster of monkeypox in a
      family with a spectrum of clinical illness, including encephalitis, and outline
      the laboratory confirmation of monkeypox. METHODS: Standardized patient
      information was collected by questionnaire and medical chart review; all cases
      described were laboratory confirmed. Laboratory methods included nucleic acid
      detection, viral culture, serologic testing, histopathologic evaluation, and
      immunohistochemical testing. RESULTS: Of 3 family members with monkeypox, 2 had
      rash illness only, and 1 required hospitalization for severe encephalitis. The
      family member with the mildest clinical course had previously received smallpox
      vaccination. Diagnostic testing by both polymerase chain reaction and culture
      revealed infectious monkeypox virus in skin lesions of all 3 patients; 2 patients
      had orthopoxvirus detected by immunohistochemistry in skin lesions. The patient
      with encephalitis had orthopoxvirus-reactive immunoglobulin M (IgM) in
      cerebrospinal fluid. All patients had detectable IgM responses to orthopoxvirus
      antigens. CONCLUSIONS: These 3 patients illustrate a spectrum of clinical illness
      with monkeypox despite a common source of exposure; manifestation and severity of
      illness may be affected by age and prior smallpox vaccination. We report that
      monkeypox, in addition to causing febrile rash illness, causes severe neurologic
      infection, and we discuss the use of novel laboratory tests for its diagnosis.

PMID- 15499542
TI  - Toll-like receptor (TLR)-3, but not TLR4, agonist protects against genital herpes
      infection in the absence of inflammation seen with CpG DNA.
AB  - We previously demonstrated that delivery of CpG oligodeoxynucleotide (ODN) to
      vaginal mucosa induced an innate mucosal antiviral state that protected against
      intravaginal challenge with herpes simplex virus (HSV)-2. We report that mucosal,
      but not systemic, delivery of ligands for Toll-like receptor (TLR)-3, but not
      TLR4, induced protection against genital HSV-2 challenge that was not accompanied
      by the local inflammation and splenomegaly seen after treatment with CpG ODN.
      Surprisingly, TLR4 messenger (m) RNA expression was shown to be higher than that
      of TLR3 or TLR9 in murine genital mucosa. Similarly, murine RAW264.7 cells were
      shown to express more mRNA for TLR4 than TLR3 or TLR9, yet treatment of these
      cells with double-stranded RNA provided greater protection than
      lipopolysaccharide or CpG ODN. These results indicate that TLR3 ligand induces a
      more potent antiviral response than TLR4 and TLR9 ligands and may be a safer
      means of protecting against sexually transmitted viral infections.

PMID- 15499543
TI  - Human milk contains elements that block binding of noroviruses to human histo
      blood group antigens in saliva.
AB  - Noroviruses (NVs) recognize human histo-blood group antigens (HBGAs) as
      receptors. We characterized the interaction of human milk samples with
      recombinant virus-like particles representing VA387, Norwalk, VA207, and MOH.
      Milk samples from 60 healthy women were tested for human HBGAs and for their
      ability to block the binding of NVs. Fifty-four women were secretors (Se+), and 6
      were nonsecretors (Se-). No women had detectable A or B antigens in their milk
      samples. All 54 Se+ milk samples, but 0 of 6 Se- milk samples, blocked VA387 and
      Norwalk virus (Se+ binders) from binding to saliva samples. All 6 Lewis-positive
      Se- milk samples blocked binding to VA207, and variable blocking activities were
      exhibited by the Se+ milk samples. No milk samples blocked the binding of MOH to
      A and B antigens. Secretor and Lewis, but not A or B antigens, were present in
      human milk and were responsible for blocking NV binding to receptors and
      therefore are likely to be decoy receptors that protect breast-fed infants from
      NV infection.

PMID- 15499544
TI  - Factors influencing increases in CD4 cell counts of HIV-positive persons
      receiving long-term highly active antiretroviral therapy.
AB  - BACKGROUND: Highly active antiretroviral therapy (HAART) results in an
      improvement in immunologic function. We sought to investigate the factors
      associated with increases in CD4 cell count among human immunodeficiency virus
      (HIV)-positive antiretroviral-naive patients starting HAART. METHODS: Five
      hundred ninety-six subjects were followed for a median of 2.5 years
      (interquartile range, 1.0-4.0 years). Factors associated with changes in CD4 cell
      counts in the first 3 months of HAART and from 3 months onwards were analyzed.
      RESULTS: After 6, 12, and 24 months of HAART, the median increases in CD4 cell
      counts were 114, 181, and 248 cells/mm3, respectively; 84%, 84%, and 80% of
      subjects had a virus load of <400 copies/mL during the same periods. White
      ethnicity, higher pre-HAART virus load, and lower pre-HAART CD4 and CD8 cell
      counts were associated with greater increases in CD4 cell counts during the first
      3 months of HAART. From 3 months onward, a greater cumulative proportion of time
      spent with virus load <400 copies/mL was associated with a more favorable change
      in CD4 cell count (an average increase of 5.2 cells/mm3/year [95% confidence
      interval [CI], 3.8-6.7 cells/mm3/year] for each extra 10% cumulative time spent
      with a virus load <400 copies/mL) (P<.0001). For every 100 cells/mm3 higher in
      baseline CD4 cell count, the increase was 6 cells/mm3/year less (95% CI, 2-11
      cells/mm3/year) (P=.02). Sex, risk group, age, and HAART regimen were not
      associated with increases in CD4 cell counts. CONCLUSIONS: These findings
      emphasize the importance of maintaining virological suppression and suggest other
      factors that influence long-term CD4 cell response.

PMID- 15499545
TI  - Helminth infection is not associated with faster progression of HIV disease in
      coinfected adults in Uganda.
AB  - BACKGROUND: We studied a cohort of human immunodeficiency virus (HIV)-infected
      adults in Uganda who were not receiving antiretroviral therapy, to explore the
      impact of helminths on HIV progression in areas where antiretrovirals are not
      available. METHODS: A total of 663 patients were screened for helminths, treated
      presumptively with albendazole and selectively with praziquantel, and monitored
      for 6 months. Blood samples were analyzed for CD4+ cell count and HIV-1 RNA.
      RESULTS: Schistosoma mansoni, hookworm, Strongyloides stercoralis, and Mansonella
      perstans were the most prevalent helminths. Helminth infection was not associated
      with higher viral load, lower CD4+ cell count, or faster decrease in CD4+ cell
      count preceding antihelminthic therapy. The effect of coinfection on HIV disease
      progression varied with species. CD4+ cell counts were highest in subjects with
      hookworm and Mansonella perstans infection. For most helminths, effective
      treatment was associated with greater decrease in CD4+ cell count than in those
      in whom infection was still present at follow-up. A highly significant decrease
      in viral load at 6 months was seen in patients with persistent Mansonella
      perstans infection at follow-up. Mortality was lower in subjects with hookworm
      infection at enrollment. CONCLUSION: Helminth infection was not associated with
      more-advanced HIV disease or faster disease progression. Antihelminthic therapy
      may not be beneficial in slowing HIV progression in coinfected adults.

PMID- 15499546
TI  - Association of levels of HIV-1-infected breast milk cells and risk of mother-to
      child transmission.
AB  - Understanding how the level of human immunodeficiency virus type 1 (HIV-1)
      infected breast milk cells (BMCs) affects HIV transmission via breast-feeding can
      shed light on the mechanism of infection and aid in establishing effective
      interventions. The proportion of infected cells to total cells was measured in
      serial breast milk samples collected from 291 HIV-1-infected women in Nairobi,
      Kenya, by use of real-time DNA polymerase chain reaction amplification of BMCs.
      The number of infected BMCs per million cells was associated with levels of cell
      free viral RNA in breast milk (R=.144; P=.032), levels of cell-free virus in
      blood plasma (R=.365; P<.001), and the detection of proviral DNA in cervical and
      vaginal secretions (P<.001 and P = .030, respectively). The number of infected
      BMCs per million cells was lower in colostrum or early milk than in mature milk
      (P<.001). Previous studies demonstrated that the concentration of BMCs varies
      throughout lactation, and we used these data to transform infected BMCs per
      million cells to infected BMCs per milliliter. The estimated concentration of
      infected BMCs per milliliter was higher in colostrum or early milk than in mature
      milk (P<.001). Each log10 increase in infected BMCs per milliliter was associated
      with a 3.19-fold-increased risk of transmission (P=.002), after adjustment for
      cell-free virus in plasma (hazard ratio [HR], 2.09; P=.03) and breast milk (HR,
      1.01; P=1.00). This suggests that infected BMCs may play a more important role in
      transmission of HIV via breast-feeding than does cell-free virus.

PMID- 15499547
TI  - Early plasmacytoid dendritic cell changes predict plasma HIV load rebound during
      primary infection.
AB  - During human immunodeficiency virus (HIV) infection, interruption of highly
      active antiretroviral therapy (HAART) is usually followed by virus load rebound.
      Previous data have suggested a role for plasmacytoid dendritic cells (pDCs) in
      anti-HIV innate immunity. Here, the number of pDCs was measured by flow cytometry
      before, during, and after receipt of HAART in 7 patients with documented primary
      HIV-1 infection. A negative correlation was evidenced between pDC counts after 1
      month of HAART and mean plasma virus load after interruption of HAART (r2=0.85;
      Spearman's partial rho =-0.92; P=.03). pDC counts during treatment might help
      predict immune replication control after interruption of HAART.

PMID- 15499549
TI  - Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5/STK9) gene are
      associated with severe neurodevelopmental retardation.
AB  - Recently, we showed that truncation of the X-linked cyclin-dependent kinase-like
      5 (CDKL5/STK9) gene caused mental retardation and severe neurological symptoms in
      two female patients. Here, we report that de novo missense mutations in CDKL5 are
      associated with a severe phenotype of early-onset infantile spasms and clinical
      features that overlap those of other neurodevelopmental disorders, such as Rett
      syndrome and Angelman syndrome. The mutations are located within the protein
      kinase domain and affect highly conserved amino acids; this strongly suggests
      that impaired CDKL5 catalytic activity plays an important role in the
      pathogenesis of this neurodevelopmental disorder. In view of the overlapping
      phenotypic spectrum of CDKL5 and MECP2 mutations, it is tempting to speculate
      that these two genes play a role in a common pathogenic process.

PMID- 15499550
TI  - Ventral otic cell lines as developmental models of auditory epithelial and neural
      precursors.
AB  - Conditionally immortal cell lines were established from the ventral otocyst of
      the Immortomouse at embryonic day 10.5 and selected to represent precursors of
      auditory sensory neural and epithelial cells. Selection was based upon
      dissection, tissue-specific markers, and expression of the transcription factor
      GATA3. Two cell lines expressed GATA3 but possessed intrinsically different
      genetic programs under differentiating conditions. US/VOT-E36 represented
      epithelial progenitors with potential to differentiate into sensory and
      nonsensory epithelial cells. US/VOT-N33 represented migrating neuroblasts. Under
      differentiating conditions in vitro the cell lines expressed very different gene
      expression profiles. Expression of several cell- and tissue-specific markers,
      including the transcription factors Pax2, GATA3, and NeuroD, differed between the
      cell lines in a pattern consistent with that observed between their counterparts
      in vivo. We suggest that these and other conditionally immortal cell lines can be
      used to study transient events in development against different backgrounds of
      cell competence.

PMID- 15499551
TI  - New experimental flap model in the rat: free flow-through epigastric flap.
AB  - This study describes a free flow-through flap model in the rat for use in the
      evaluation of the physiologic and hemodynamic characteristics of this type of
      flap in clinical practice. The rat is a preferred animal model because it is
      inexpensive, readily available, and reliable. There is no free flow-through flap
      model available for laboratory animals, although this model gained popularity in
      clinical use recently. Twenty Wistar rats weighing 200-250 g were used in our
      experiment. In 5 rats, the vascular anatomy of the groin and proximal thigh
      region was determined by anatomic dissection. The experimental design consisted
      of two groups. In the experimental group (N = 5), a flow-through epigastric skin
      flap was harvested based on the femoral artery, preparing both its proximal and
      distal stumps. The flap was transferred to the contralateral groin, and end-to
      end vascular anastomosis was performed between a proximal and distal stump of the
      femoral arteries of the flap and recipient site. The proximal stump of the
      femoral vein of the flap was anastomosed to the femoral vein of the recipient
      site. The control group was divided into two subgroups. In all control group rats
      (N = 10), the flap was harvested in the same manner, and transferred to the
      contralateral groin, but standard free-flap procedure with one artery and one
      vein anastomosis was performed in 5 rats (conventional free-flap subgroup), and
      anastomosis was not performed between the flap and the recipient site in the
      remaining 5 rats (graft subgroup). Survival of the flap was evaluated on
      postoperative day 7 by direct observation, and microangiography was performed to
      delineate the vascularity of the flow-through flap. The results showed that all
      flaps survived in the experimental group and the conventional free-flap subgroup
      of the control group, whereas in the graft subgroup, all flaps underwent total
      necrosis. The authors conclude that the flow-through epigastric flap for the rat
      is a simple and reliable model for future physiologic and pharmacologic studies.

PMID- 15499552
TI  - Heterotopic limb allotransplantation model to study skin rejection in the rat.
AB  - Current rodent models for investigation of limb allotransplantation typically
      utilize orthotopic whole-limb transplantation, a morbid and time-consuming
      procedure. Our objective was to design a less morbid rat model to explore the
      immunological obstacles of limb transplantation, and particularly skin. Twenty
      lower hindlimbs from 10 donors were transplanted into a heterotopic subcutaneous
      position into 20 animals (10 isogeneic and 10 allogeneic). Each group was further
      subdivided to include animals with (n = 5) and without (n = 5) a skin paddle for
      observation of cutaneous signs of rejection. All grafts in the isogeneic group
      survived for 100 days, i.e., the endpoint of the study. Allogeneic transplants
      rejected their allografts at a mean of 12.8 days (with skin) and 20.6 days
      (without). Our heterotopic limb transplantation model takes less time and is less
      stressful to the animals, while allowing for early observation of graft skin
      rejection, when compared to orthotopic whole-limb transplantation.

PMID- 15499553
TI  - Intraoperative magnification: Who uses it?
AB  - Surgeons over recent decades have made increasing use of intraoperative
      magnification to enhance the outcome of surgical procedures, yet no published
      information exists regarding the extent of magnification use within surgical
      specialties. A sample of surgeons consisting of 148 specialists and senior
      surgical trainees in the west of Scotland was surveyed by postal questionnaire
      regarding their frequency and types of magnification use. Patterns of use were
      similar within each specialty, but varied markedly between specialties.
      Otolaryngologists and plastic, maxillofacial, and ophthalmic surgeons use both
      loupes and microscopes frequently. Cardiothoracic and pediatric surgeons tend
      only to utilize loupes, whereas neurosurgeons tend only to use microscopes.
      General surgeons, urologists, orthopedic surgeons, and gynecologists are
      infrequent users or nonusers of magnification, and when required will utilize
      loupes rather than microscopes. As a clear pattern of magnification use exists,
      it should be possible to anticipate the equipment needs of surgeons when
      providing theater services.

PMID- 15499554
TI  - Msx2 controls ameloblast terminal differentiation.
AB  - Late tooth morphogenesis is characterized by a series of events that determine
      cusp morphogenesis and the histodifferentiation of epithelial cells into enamel
      secreting ameloblasts. Mice lacking the homeobox gene Msx2 exhibit defects in
      cusp morphogenesis and in the process of amelogenesis. To better understand the
      basis of the Msx2 mutant tooth defects, we have investigated the function of Msx2
      during late stages of tooth morphogenesis. Cusp formation is thought to be under
      the control of the enamel knot, which has been proposed to act as an organizing
      center during this process (Vaahtokari et al. [ 1996] Mech. Dev. 54:39-43). Bone
      morphogenetic protein-4 (BMP4) has been suggested to mediate termination of
      enamel knot signaling by means of regulation of programmed cell death (Jernvall
      et al. [ 1998] Development 125:161-169). Here, we show that Bmp4 expression in
      the enamel knot is Msx2-dependent. We further show that during amelogenesis Msx2
      is required for the expression of the extracellular matrix gene Laminin 5 alpha
      3, which is known to play an essential role during ameloblast differentiation.
      This result thus provides a paradigm for understanding how transcription factors
      and extracellular matrix can be integrated into a developmental pathway
      controlling cell differentiation.

PMID- 15499555
TI  - Interleukin-11 signaling is required for the differentiation of natural killer
      cells at the maternal-fetal interface.
AB  - Interleukin-11 (IL-11) is a multifunctional hematopoietic growth factor that has
      been implicated in the control of reproduction. Studies on IL-11 receptor-alpha
      (IL-11R alpha)-deficient mice showed that female mice are infertile due to
      defective decidualization. In this report, we evaluated the development of
      decidual cells, immune cells, and the vasculature associated with the
      implantation site of IL-11R alpha-deficient mice; with the aim of better
      understanding the nature of the fertility defect. Messenger RNAs for decidual
      differentiation, such as decidual prolactin-related protein and prolactin-like
      protein-J are expressed in the IL-11R alpha mutant. However, the number of
      decidual cells expressing these genes is decreased in the mutant compared with
      the wild-type control. Although, trophoblast cells differentiate and express
      placental lactogen-I in the IL-11R alpha-deficient uterine environment, they fail
      to progress and expand in number. Defects in the organization of the decidual
      vasculature were also apparent in the IL-11R alpha mutant uterus. The most
      dramatic effect of IL-11 signaling was on the hematopoietic environment of the
      uterine decidua. Differentiated/perforin-expressing uterine natural killer (NK)
      cells were virtually absent from implantation sites of IL-11R alpha mutant mice.
      NK cell precursors were capable of homing to the IL-11R alpha-deficient uterus
      and a known regulator of NK cell differentiation; IL-15 was expressed in the IL
      11R alpha mutant uterus. Splenic NK cells from IL-11R alpha mutant mice were also
      able to respond to IL-15 in vitro. Thus, the defect in NK precursor cell
      maturation was not intrinsic to the NK precursor cells but was dependent upon the
      tissue environment. In summary, IL-11 signaling is required for decidual-specific
      maturation of NK cells.

PMID- 15499556
TI  - Myogenic regulatory factors: redundant or specific functions? Lessons from
      Xenopus.
AB  - The discovery, in the late 1980s, of the MyoD gene family of muscle transcription
      factors has proved to be a milestone in understanding the molecular events
      controlling the specification and differentiation of the muscle lineage. From
      gene knock-out mice experiments progressively emerged the idea that each myogenic
      regulatory factor (MRF) has evolved a specialized as well as a redundant role in
      muscle differentiation. To date, MyoD serves as a paradigm for the MRF mode of
      function. The features of gene regulation by MyoD support a model in which
      subprograms of gene expression are achieved by the combination of promoter
      specific regulation of MyoD binding and MyoD-mediated binding of various
      ancillary proteins. This binding likely includes site-specific chromatin
      reorganization by means of direct or indirect interaction with remodeling
      enzymes. In this cascade of molecular events leading to the proper and
      reproducible activation of muscle gene expression, the role and mode of function
      of other MRFs still remains largely unclear. Recent in vivo findings using the
      Xenopus embryo model strongly support the concept that a single MRF can
      specifically control a subset of muscle genes and, thus, can be substituted by
      other MRFs albeit with dramatically lower efficiency. The topic of this review is
      to summarize the molecular data accounting for a redundant and/or specific
      involvement of each member of the MyoD family in myogenesis in the light of
      recent studies on the Xenopus model.

PMID- 15499557
TI  - Mouse myotomes pairs exhibit left-right asymmetric expression of MLC3F and alpha
      skeletal actin.
AB  - Most muscle originates from the myotomal compartment of the somites, paired
      structures flanking the neural tube. Whereas vertebrate embryos show molecular
      and morphological asymmetry about the left-right body axis, somitic myogenesis is
      thought to occur symmetrically. Here, we provide the first evidence that myotome
      pairs are transiently left-right asymmetric, with higher expression of alpha
      skeletal actin and myosin light chain 3F (MLC3F) on the left side between
      embryonic day 9.5-10.25. In iv mutants with situs inversus, the asymmetric
      expression of alpha-skeletal actin and MLC3F was inverted, showing that this
      process is regulated by global left-right axis cues, initiated before
      gastrulation. However, although left-sided identity is later maintained by Pitx2
      genes, we found that Pitx2c null embryos have normal left-biased expression of
      alpha-skeletal actin and MLC3F. Myotome asymmetry, therefore, is downstream of
      the iv mutation but upstream of, or unrelated to, the Pitx2c pathway.

PMID- 15499558
TI  - Synthesis of spiro[5.4]decenones and their transformation into bicyclo[4.4]deca
      1,4-dien-3-ones by domino "elimination- double-Wagner-Meerwein-rearrangement"
      reactions.
AB  - The [3+3] cyclization of 1,3-bis-silyl enol ethers with 1,1-diacylcyclopentanes
      allows a convenient synthesis of spiro[5.4]decenones. Treatment of these
      compounds with trifluoroacetic acid (TFA) afforded a great variety of
      bicyclo[4.4.0]deca-1,4-dien-3-ones containing an angular alkyl group. This core
      structure occurs in a number of pharmacologically relevant natural products.

PMID- 15499559
TI  - Early fin primordia of zebrafish larvae regenerate by a similar growth control
      mechanism with adult regeneration.
AB  - Some vertebrate species, including urodele amphibians and teleost fish, have the
      remarkable ability of regenerating lost body parts. Regeneration studies have
      been focused on adult tissues, because it is unclear whether or not the repairs
      of injured tissues during early developmental stages have the same molecular base
      as that of adult regeneration. Here, we present evidence that a similar cellular
      and molecular mechanism to adult regeneration operates in the repair process of
      early zebrafish fin primordia, which are composed of epithelial and mesenchymal
      cells. We show that larval fin repair occurs through the formation of wound
      epithelium and blastema-like proliferating cells. Cell proliferation is first
      induced in the distal-most region and propagates to more proximal regions, as in
      adult regeneration. We also show that fibroblast growth factor signaling helps
      induce cell division. Our results suggest that the regeneration machinery
      directing cell proliferation in response to injury may exist from the early
      developmental stages.

PMID- 15499560
TI  - Partially overlapping expression of Gata2 and Gata3 during inner ear development.
AB  - Gata2 and Gata3 belong to the Gata family of transcription factors in vertebrates
      that bind to a consensus "GATA" DNA sequence. The Gata3 gene is one of the
      earliest markers for the developing mouse inner ear. Ear morphogenesis is blocked
      in Gata3-deficient embryos, whereas nothing was known of the role of Gata2 in
      mouse inner ear. Here, we have compared the expression patterns of Gata2 and
      Gata3 during normal inner ear development and investigated their relationship in
      mice where either Gata3 or Gata2 has been inactivated. The expression of the two
      Gata genes is highly overlapping at embryonic day (E)10.5 but becomes
      increasingly distinct later. Whereas Gata2 is predominantly expressed in the
      dorsal vestibular system, Gata3 was detected mainly in the ventral cochlear duct
      and ganglion. No phenotypic abnormalities were observed in the inner ear of Gata2
      /- embryos before lethality at E10.5 and Gata3 expression was unchanged. In
      contrast, a delay and strong reduction of Gata2 expression was detected in Gata3
      /- otic epithelium.

PMID- 15499561
TI  - Differential expression of heparan sulfate 6-O-sulfotransferase isoforms in the
      mouse embryo suggests distinctive roles during organogenesis.
AB  - Heparan sulfate (HS) interactions with secreted morphogens such as fibroblast
      growth factors, hedgehogs, and Wnts are essential for embryonic development.
      Formation of biologically relevant HS structures is a result of the coordinated
      action of various biosynthetic enzymes. HS 6-O-sulfotransferases (6OST) catalyze
      the transfer of sulfate groups to the 6-O position of glucosamine residues in HS.
      Three 6OST isoforms have been described in the mouse; however, little is known
      about their role in generating specific HS protein-binding sequences, expression
      pattern, and function in vivo. To gain insights into the distribution of these
      isoforms and their potential role in development, we mapped 6OST1-3 gene
      expression during mouse organogenesis. We report dynamic expression of these
      isoforms with striking differences in tissue distribution in many developing
      organs. We show that 6OST transcripts are differentially expressed in several
      sites where heparin-binding growth factors are critical for development. 6OST1 is
      predominantly transcribed in epithelial and neural-derived tissues, whereas 6OST2
      is more mesenchymal. 6OST3 appears at later stages and in a more restricted
      manner. The patterns reported here strongly suggest that the HS structures
      modified by these enzymes have different roles in growth factor-induced
      developmental processes.

PMID- 15499562
TI  - Coexpression of Cux-1 and Notch signaling pathway components during kidney
      development.
AB  - Cux-1 is the murine homologue of the Drosophila gene cut, which is required for
      cellular differentiation in several tissues, including the wing margin and
      Malpighian tubule. Mammalian cut proteins function as cell cycle-dependent
      transcriptional repressors in proliferating cells. Targets of Cux-1 repression
      include the cyclin kinase inhibitors p21 and p27. However, little is known about
      the regulation of Cux-1. In Drosophila, multiple genetic interactions between Cut
      and the Notch and Wingless signaling pathways occur during wing development. To
      begin to determine whether Cux-1 regulation by the Notch signaling pathway is
      conserved in mammals, we compared the expression patterns of Cux-1, the murine
      Notch receptors (Notch 1-4), and the murine ligands (Jagged 1, Jagged 2, and
      Delta 1) during murine embryogenesis and kidney development. In this report, we
      demonstrate that Cux-1 expression overlaps with that of Notch signaling pathway
      components in multiple tissues during embryonic development. In the developing
      kidney, Cux-1 expression overlaps with that of Notch pathway components in the
      condensing mesenchyme, in pretubular aggregates (comma and S-shaped bodies), and
      in the presumptive podocytes of capillary loop stage glomeruli. Furthermore, Cux
      1 was significantly up-regulated in the rat kidney epithelial cell line RKE
      expressing a constitutively active Notch 1, and this finding was associated with
      a reduction of p27. Moreover, Cux-1 interacts with the Groucho homolog TLE-4, a
      corepressor recruited by Notch effector proteins. Taken together, these results
      suggest that Cux-1 may function in the context of the Notch signaling pathway in
      multiple tissues during mammalian embryogenesis.

PMID- 15499563
TI  - Induction of signaling pathways by herpes simplex virus type 1 through
      glycoprotein H peptides.
AB  - Eukaryotic cells respond to extracellular stimuli, such as viruses, by recruiting
      signal transduction pathways, many of which are mediated through activation of
      distinct mitogen-activated protein kinase (MAPK) cascades and activation of
      transductional regulation factors. The best characterized of this pathway are the
      extracellular signal regulated kinase (ERK), the c-Jun N-terminal kinase/stress
      activated protein kinase (JNK/SAPK), and the p38 MAPK cascade. Herpes simplex
      virus type 1 (HSV-1) encodes at least 11 envelope glycoproteins, which alone or
      in concert play different roles in viral adsorption, entry, cell-to-cell spread,
      and immune evasion. Of these proteins, three are designated glycoprotein B (gB),
      glycoprotein D (gD), and the gH/gL heterodimer, are clearly involved in
      attachment and entry, and therefore possible candidates in inducing early
      cellular activation.Nevertheless, the precise role of each glycoprotein and the
      cellular factor involved remain elusive. The signal transduction pathways
      involved, and the outcome of cellular activation on viral entry or postentry
      events, are still to be elucidated. To better understand the role of signal
      transduction pathways and phosphorylation events in HSV-1 entry, synthetic
      peptides modeled on HSV-1 gH were synthesized and tested for MEK1-MEK2/MAPK
      cascade activation. Our results show a major involvement of the JNK pathway in
      the intracellular signal transmission after stimulation with gH HSV-1 peptides.

PMID- 15499564
TI  - Polypeptide conjugates comprising a beta-amyloid plaque-specific epitope as new
      vaccine structures against Alzheimer's disease.
AB  - Immunotherapeutic approaches designed to induce a humoral immune response have
      recently been developed for possible vaccination to the treatment of Alzheimer's
      disease (AD). Based on the identification of Abeta(4-10) (FRHDSGY) as the
      predominant B-cell epitope recognized by therapeutically active antisera from
      transgenic AD mice, branched polypeptide conjugates with this epitope peptide
      were synthesized and characterized. In order to produce immunogenic constructs,
      the Abeta(4-10) epitope alone or together with a promiscuous T-helper cell
      epitope peptide (FFLLTRILTIPQSLD) were attached via thioether linkage to
      different branched chain polymeric polypeptides with Ser or Glu in the side
      chains. A single peptide containing both an Abeta(4-10) and T-helper cell
      epitope, joined by a dipeptide Cys-Acp spacer, was also attached through the
      thiol function to chloroacetylated poly[Lys(Seri-DL-Alax)] (SAK). Comparative
      binding studies of the conjugates with a monoclonal antibody against the beta
      amyloid(1-17) peptide in mice were performed by direct ELISA. The conformational
      preferences of carriers and conjugates in water and in a 9:1
      trifluoroethanol:water mixture (v/v) was analyzed by CD spectroscopy.
      Experimental data showed that the chemical nature of the carrier macromolecule,
      and the attachment site of the epitope to the carrier, have significant effects
      on antibody recognition, but have no marked influence on the solution
      conformation of the conjugates.

PMID- 15499565
TI  - A synthetic peptide reproducing the mitochondrial targeting motif of AKAP121: a
      conformational study.
AB  - The conformational features of a peptide derived by the 10-30 sequence of the
      mitochondrial domain of AKAP121 [Ac-1XKKPLALPGMLALLGWWWFFSRKKX25-NH2 (X=beta
      Ala)] in water and in a water/trifluoroethanol (TFE) mixture at 298 K have been
      determined by NMR and CD spectroscopy. Backbone clustering analysis of NMR
      derived structures led to the identification of a single representative structure
      in water/TFE. The structure of the peptide consists mainly of an alpha-helix,
      whose core is the region 7-23, with a less ordered N-terminal part. These data
      are confirmed by CD analysis. It is noteworthy that the high hydrophobic Trp16
      Phe20 segment, that might also mediate interaction with tubulin, is organized in
      an alpha-helical wheel. Our conformational data can be the starting point for the
      development of highly selective peptides that interfere with the biological
      function of the Protein Kinase A scaffold protein AKAP121.

PMID- 15499566
TI  - Total synthesis in solution of alamethicin F50/5 by an easily tunable segment
      condensation approach.
AB  - A total synthesis in solution of the 19-mer peptide component F50/5 of
      alamethicin, the most extensively investigated among the channel-former peptaibol
      antibiotics, is reported. Three peptide segments (A, B, C) were prepared and
      assembled, followed by incorporation of the acetylated N-terminal amino acid. The
      synthetic modules B and C are characterized by three Glu(OMe) residues (at
      positions 7, 18, and 19) that, after completion of the synthesis, were reacted
      with ammonia to provide alamethicin F50/5. By use of this general strategy, we
      also prepared the [Gln7, Glu(OMe)18,19] alamethicin F50/5 analogue. The purity
      and conformation of the final products were assessed by chromatographic,
      spectrometric, and spectroscopic techniques. This tunable segment condensation
      approach will pave the way for an easy synthesis of alamethicin analogues bearing
      amino acid residues with desired side-chain probes even at the N-terminus and in
      internal positions of the sequence.

PMID- 15499567
TI  - Generalized Poland-Scheraga model for DNA hybridization.
AB  - The Poland-Scheraga (PS) model for the helix-coil transition of DNA considers the
      statistical mechanics of the binding (or hybridization) of two complementary
      strands of DNA of equal length, with the restriction that only bases with the
      same index along the strands are allowed to bind. In this article, we extend this
      model by relaxing these constraints: We propose a generalization of the PS model
      that allows for the binding of two strands of unequal lengths N1 and N2 with
      unrelated sequences. We study in particular (i) the effect of mismatches on the
      hybridization of complementary strands, (ii) the hybridization of
      noncomplementary strands (as resulting from point mutations) of unequal lengths
      N1 and N2. The use of a Fixman-Freire scheme scales down the computational
      complexity of our algorithm from O(N1(2)N2(2) to O(N1N2). The simulation of
      complementary strands of a few kilo base pairs yields results almost identical to
      the PS model. For short strands of equal or unequal lengths, the binding displays
      a strong sensitivity to mutations. This model may be relevant to the experimental
      protocol in DNA microarrays, and more generally to the molecular recognition of
      DNA fragments. It also provides a physical implementation of sequence alignments.

PMID- 15499568
TI  - Encapsulation of biologics in self-assembled fibers as biostructural units for
      tissue engineering.
AB  - The concept of a "biostructural unit" is presented as the combination of
      biological and structural building blocks to create scaffolds or constructs via a
      bottom-up approach. Three types of biostructural units were constructed using the
      process of fiber formation by interfacial polyelectrolyte complexation: protein
      encapsulated fiber, ligand-immobilized fiber, and cell-encapsulated fiber units.
      Water-soluble chitin (WSC) and alginate were used as the polyelectrolyte
      combination to form fiber. Encapsulation and sustained release of bovine serum
      albumin from the fiber could be achieved, release profiles being dependent on the
      WSC/alginate concentration ratio. Released nerve growth factor (NGF) retained its
      bioactivity, as demonstrated on PC12 cells. Biotinylated fiber could be
      fabricated by biotinylating alginate before drawing fiber with WSC, enabling
      biotinylated NGF to be immobilized to fiber via an avidin bridge. The immobilized
      NGF induced the differentiation of PC12 cells seeded on the fiber. Bovine
      pulmonary endothelial cells, human dermal fibroblasts, and human mesenchymal stem
      cells were encapsulated, demonstrating good viability as determined by Live/Dead
      and WST-1 assays. The assembly of biostructural units into constructs was
      illustrated by using human mesenchymal stem cell-encapsulated fiber units. Cells
      in the resulting constructs could be induced to differentiate along chondrogenic
      and osteogenic lineages.

PMID- 15499569
TI  - siRNA mediated inhibition of MMP-1 reduces invasive potential of a human
      chondrosarcoma cell line.
AB  - Matrix metalloproteinases (MMPs) play a crucial role in tumor cell invasion and
      metastasis. Expression of MMP-1 has been reported as a prognostic predictor of
      recurrence in human chondrosarcoma, and studies using human chondrosarcoma cell
      lines indicate that MMP-1 expression levels correlate with in vitro invasiveness.
      These observations suggest that MMP-1 activity has a central role in cell egress
      from the primary tumor at an early step in the metastatic cascade. In this study,
      siRNA was used to investigate whether knock down of the MMP-1 gene could be used
      to inhibit invasiveness in a human chondrosarcoma cell line. The inhibitory
      effect of siRNA on endogenous MMP-1 gene expression and protein synthesis was
      demonstrated via RT-PCR, Northern blotting, Western blotting, collagenase
      activity assay, and an in vitro cell migration assay. The siRNA inhibited MMP-1
      expression specifically, since it did not affect the expression of endogenous
      glyceraldehyde phosphate dehydrogenase (GAPDH) nor other collagenases. Most
      importantly, the siRNA mediated reduction in MMP-1 expression correlated with a
      decreased ability of chondrosarcoma cells to invade a Type I collagen matrix. The
      reduction of invasive behavior demonstrated by human chondrosarcoma cells
      transfected with MMP-1 siRNA and the specificity of this inhibition supports the
      hypothesis that this metalloproteinase molecule is involved in initiation of
      chondrosarcoma metastasis.

PMID- 15499570
TI  - Expression, location, and interactions of ErbB2 and its intramembrane ligand Muc4
      (sialomucin complex) in rat mammary gland during pregnancy.
AB  - Muc4 (also called Sialomucin complex) is a heterodimeric glycoprotein complex
      consisting of a peripheral O-glycosylated subunit ASGP-1 (ascites
      sialoglycoprotein-1) tightly but non-covalently bound to an N-glycosylated
      transmembrane subunit ASGP-2. Muc4/SMC can act as an intramembrane ligand for
      ErbB2 via an EGF-like domain present in the transmembrane subunit. The complex is
      developmentally regulated in normal rat mammary gland and overexpressed in a
      number of mammary tumors. Overexpression of Muc4/SMC has been shown to block cell
      cell and cell-matrix interactions, protect tumor cells from immune surveillance,
      promote metastasis, and protect from apoptosis. We have investigated whether
      Muc4/SMC and ErbB2 are co-expressed and co-localized in normal rat mammary gland
      and whether Muc4/SMC-ErbB2 complex formation is developmentally regulated in this
      tissue. Muc4/SMC and ErbB2 have different expression patterns and regulatory
      mechanisms in the developing rat mammary gland, but both are maximally expressed
      during late pregnancy and lactation. The two proteins form a complex in lactating
      mammary gland which is not detected in the virgin gland. Moreover, this complex
      does not contain ErbB3. ErbB2 is co-localized with Muc4/SMC at the apical
      surfaces of ductal and alveolar cells in lactating gland; however, another form
      of ErbB2, recognized by a different antibody, localizes to the basolateral
      surfaces of these cells. ErbB2 phosphorylated on Tyr 1248 co-localized with
      Muc4/SMC at the apical surface but not at the basolateral surfaces of these
      cells. To investigate the function of Muc4 in the mammary gland, transgenic mice
      were derived using an MMTV-Muc4 construct. Interestingly, mammary gland
      development in the transgenic mice was aberrant, exhibiting a bifurcated pattern,
      including invasion down the blood vessel, similar to that exhibited by transgenic
      mice inappropriately expressing activated ErbB2 in the mammary gland. These data
      provide further evidence of the ability of Muc4/SMC to interact with ErbB2 and
      influence its behavior in normal epithelia.

PMID- 15499571
TI  - Internalization and trafficking of the human and rat growth hormone-releasing
      hormone receptor.
AB  - Internalization and intracellular trafficking of the growth hormone-releasing
      hormone receptor (GHRH-R) were studied in rat anterior pituitary and human (h)
      and rat (r) GHRH-R-transfected BHK cells, with the GHRH agonist, [N(alpha)-5
      carboxyfluoresceinyl-D-Ala(2), Ala(8), Ala(15), Lys(22)]hGHRH(1-29)NH(2) (Fluo
      GHRH). Time- and temperature-dependent internalization of stimulated GHRH-R was
      blocked by phenyl arsine oxide (PAO) in both cell types. In anterior pituitary
      and rGHRH-R-transfected BHK cells, only filipin III and cerulenin blocked
      receptor-mediated internalization of Fluo-GHRH while in hGHRH-R-transfected BHK
      cells, only hyperosmolar sucrose inhibited this process. These results suggest
      that hGHRH-R internalization is clathrin-dependent, while fatty acid acylation of
      rGHRH-R appears to be a prerequisite to caveolin-dependent internalization.
      Experiments in anterior pituitary using Bodipy-FL-C(5) ganglioside GM1, a
      specific marker of lipid rafts such as caveolae, confirmed this latter pathway.
      Co-localization of Fluo-GHRH with LysoTracker indicated that Fluo-GHRH was
      directed to acidic organelles in both cell types. Finally, studies using
      cycloheximide and monensin showed that upon stimulation with GHRH, an optimal
      concentration of functional GHRH-R was maintained at the plasma membrane due to
      de novo synthesis and recycling in pituitary cells and to de novo synthesis
      solely in hGHRH-R-transfected BHK cells. This first study on the dynamics of the
      GHRH/GHRH-R complexes using fluorescence imaging in a native environment compared
      to cell system models, revealed that both receptor primary structure and
      concentration at the plasma membrane play important roles in internalization and
      trafficking of specific G-protein-coupled receptors (GPCR).

PMID- 15499572
TI  - PKC/MAPK signaling suppression by retinal pericyte conditioned medium prevents
      retinal endothelial cell proliferation.
AB  - Little is known about the regulation mechanism of endothelial cell proliferation
      by retinal pericytes. The purpose of this study was to elucidate the suppression
      mechanism of retinal capillary endothelial cell growth by soluble factors derived
      from retinal pericytes. Conditioned medium of retinal pericytes (rPCT1-CM)
      suppressed ischemia-induced retinal neovascularization. The growth and DNA
      synthesis of TR-iBRB2 cells, a conditionally immortalized rat retinal capillary
      endothelial cell line, were suppressed in a concentration-dependent manner by
      concentrated rPCT1-CM. The number of human cultured endothelial cells was also
      reduced by rPCT1-CM. These results provide the first evidence that CM from the
      cultivation of pericytes alone can inhibit retinal neovascularization in vivo and
      in vitro. Although the growth reduction of TR-iBRB2 cells was only partly
      reversed by treatment of rPCT1-CM with antibodies to transforming growth factor
      beta1, it was completely lost by heat-treatment of rPCT1-CM, suggesting that anti
      angiogenic factors are soluble proteins. The levels of expression of G1/S-phase
      related proteins, such as cyclin D1, cyclin-dependent kinase (cdk)4, cdk6, and
      proliferating cell nuclear antigen, were reduced and a cdk inhibitor, p21(Cip1),
      was induced in rPCT1-CM-treated TR-iBRB2 cells. Moreover, phosphorylated p44/42
      mitogen-activated protein kinase (p44/42 MAPK) in TR-iBRB2 cells was reduced by
      rPCT1-CM treatment and phosphorylated protein kinase C (PKC)alpha/betaII, which
      is upstream of p44/42 MAPK, was also suppressed. In conclusion, CM from retinal
      pericytes suppresses PKC-p44/42 MAPK signaling, inhibits endothelial cell growth,
      and prevents retinal neovascularization. Anti-angiogenic factors derived from
      retinal pericytes are likely to play a critical role in the regulation of retinal
      endothelial cell growth.

PMID- 15499573
TI  - Detection of lymph node micrometastasis in gastric cancer by MUC2 RT-PCR:
      usefulness in pT1 cases.
AB  - BACKGROUND AND OBJECTIVES: The objectives of this study were to evaluate the
      clinical utility of MUC2-specific reverse transcriptase-polymerase chain reaction
      (RT-PCR) in gastric cancer patients and to compare MUC2-specific RT-PCR to
      carcinoembryonic antigen (CEA)-specific RT-PCR. METHODS: A total of 305 lymph
      nodes from 28 patients with gastric cancer were histologically examined and
      analyzed by MUC2 RT-PCR and CEA RT-PCR. RESULTS: MUC2 and CEA were expressed in
      17.1 and 7.0% of the 286 histologically negative lymph nodes, respectively. The
      detection rate of MUC2 was significantly higher than that of CEA (P < 0.01). MUC2
      RT-PCR revealed no false positive results in control specimens. Lymph node
      micrometastases in pT1 gastric cancer were expressed only in perigastric lymph
      nodes near the tumor and were not detected in tumor less than 30 mm in patients
      with mucosal cancer. CONCLUSIONS: MUC2-specific RT-PCR is a sensitive and
      specific method to detect lymph node micrometastases in gastric cancer patients.
      The distribution of lymph node micrometastases detected by this method may be
      useful in minimally invasive procedures for gastric cancer, especially pT1 cases.

PMID- 15499574
TI  - A serotonin receptor antagonist induces oocyte maturation in both frogs and mice:
      evidence that the same G protein-coupled receptor is responsible for maintaining
      meiosis arrest in both species.
AB  - Accumulating evidence has indicated that vertebrate oocytes are arrested at late
      prophase (G2 arrest) by a G protein coupled receptor (GpCR) that activates
      adenylyl cyclases. However, the identity of this GpCR or its regulation in G2
      oocytes is unknown. We demonstrated that ritanserin (RIT), a potent antagonist of
      serotonin receptors 5-HT2R and 5-HT7R, released G2 arrest in denuded frog
      oocytes, as well as in follicle-enclosed mouse oocytes. In contrast to RIT,
      several other serotonin receptor antagonists (mesulergine, methiothepine, and
      risperidone) had no effect on oocyte maturation. The unique ability of RIT, among
      serotonergic antagonists, to induce GVBD did not match the antagonist profile of
      any known serotonin receptors including Xenopus 5-HT7R, the only known G(s)
      coupled serotonin receptor cloned so far in this species. Unexpectedly, injection
      of x5-HT7R mRNA in frog oocytes resulted in hormone-independent frog oocyte
      maturation. The addition of exogenous serotonin abolished x5-HT7R-induced oocyte
      maturation. Furthermore, the combination of x5-HT7R and exogenous serotonin
      potently inhibited progesterone-induced oocyte maturation. These results provide
      the first evidence that a G-protein coupled receptor related to 5-HT7R may play a
      pivotal role in maintaining G2 arrest in vertebrate oocytes.

PMID- 15499575
TI  - Modification of plant N-glycans processing: the future of producing therapeutic
      protein by transgenic plants.
AB  - Transgenic plants are regarded as one of the most promising systems for the
      production of human therapeutic proteins. The number of therapeutic proteins
      successfully produced in plants is steadily arising. However, the glycoproteins
      normally produced from plants are not the same as native therapeutic proteins
      produced from mammals or humans. In addition to in vitro enzymatic modeling
      glycoproteins, there are two gene manipulation strategies to humanize plant N
      glycans connected to the glycoproteins. One is retaining the recombinant
      glycoproteins in endoplasmic reticulum (ER), the site where few specific
      modifications of N-glycans occurs. The other is inhibiting the plant endogenous
      Golgi glycosyltransferase and/or adding new glycosyltransferase from mammalians.
      In this review, the biosynthesis of N-glycans in plants, the modification of the
      plant N-glycans processing will be discussed.

PMID- 15499576
TI  - Effects of electroacupuncture versus manual acupuncture on the human brain as
      measured by fMRI.
AB  - The goal of this functional magnetic resonance imaging (fMRI) study was to
      compare the central effects of electroacupuncture at different frequencies with
      traditional Chinese manual acupuncture. Although not as time-tested as manual
      acupuncture, electroacupuncture does have the advantage of setting stimulation
      frequency and intensity objectively and quantifiably. Manual acupuncture,
      electroacupuncture at 2 Hz and 100 Hz, and tactile control stimulation were
      carried out at acupoint ST-36. Overall, electroacupuncture (particularly at low
      frequency) produced more widespread fMRI signal increase than manual acupuncture
      did, and all acupuncture stimulations produced more widespread responses than did
      our placebo-like tactile control stimulation. Acupuncture produced hemodynamic
      signal increase in the anterior insula, and decrease in limbic and paralimbic
      structures including the amygdala, anterior hippocampus, and the cortices of the
      subgenual and retrosplenial cingulate, ventromedial prefrontal cortex, frontal,
      and temporal poles, results not seen for tactile control stimulation. Only
      electroacupuncture produced significant signal increase in the anterior middle
      cingulate cortex, whereas 2-Hz electroacupuncture produced signal increase in the
      pontine raphe area. All forms of stimulation (acupuncture and control) produced
      signal increase in SII. These findings support a hypothesis that the limbic
      system is central to acupuncture effect regardless of specific acupuncture
      modality, although some differences do exist in the underlying neurobiologic
      mechanisms for these modalities, and may aid in optimizing their future usage in
      clinical applications.

PMID- 15499577
TI  - Repair of exocyclic DNA adducts: rings of complexity.
AB  - Exocyclic DNA adducts are mutagenic lesions that can be formed by both exogenous
      and endogenous mutagens/carcinogens. These adducts are structurally analogs but
      can differ in certain features such as ring size, conjugation, planarity and
      substitution. Although the information on the biological role of the repair
      activities for these adducts is largely unknown, considerable progress has been
      made on their reaction mechanisms, substrate specificities and kinetic properties
      that are affected by adduct structures. At least four different mechanisms appear
      to have evolved for the removal of specific exocyclic adducts. These include base
      excision repair, nucleotide excision repair, mismatch repair, and AP endonuclease
      mediated repair. This overview highlights the recent progress in such areas with
      emphasis on structure-activity relationships. It is also apparent that more
      information is needed for a better understanding of the biological and structural
      implications of exocyclic adducts and their repair.

PMID- 15499578
TI  - Recent developments in computational approaches for uncovering genomic homology.
AB  - Identifying genomic homology within and between genomes is essential when
      studying genome evolution. In the past years, different computational techniques
      have been developed to detect homology even when the actual similarity between
      homologous segments is low. Depending on the strategy used, these methods search
      for pairs of chromosomal segments between which either both gene content and
      order are conserved or gene content only. However, due to fact that, after their
      divergence, homologous segments can lose a different set of genes, these methods
      still often fail to detect genomic homology. Recently, more advanced approaches
      have been developed that can combine gene order and content information of
      multiple genomic segments.

PMID- 15499579
TI  - Chromosome rearrangements resulting from telomere dysfunction and their role in
      cancer.
AB  - Telomeres play a vital role in protecting the ends of chromosomes and preventing
      chromosome fusion. The failure of cancer cells to properly maintain telomeres can
      be an important source of the chromosome instability involved in cancer cell
      progression. Telomere loss results in sister chromatid fusion and prolonged
      breakage/fusion/bridge (B/F/B) cycles, leading to extensive DNA amplification and
      large deletions. These B/F/B cycles end primarily when the unstable chromosome
      acquires a new telomere by translocation of the ends of other chromosomes. Many
      of these translocations are nonreciprocal, resulting in the loss of the telomere
      from the donor chromosome, providing a mechanism for transfer of instability from
      one chromosome to another until a chromosome acquires a telomere by a mechanism
      other than nonreciprocal translocation. B/F/B cycles can also result in other
      forms of chromosome rearrangements, including double-minute chromosomes and large
      duplications. Thus, the loss of a single telomere can result in instability in
      multiple chromosomes, and generate many of the types of rearrangements commonly
      associated with human cancer.

PMID- 15499580
TI  - From modulator to mediator: rapid effects of BDNF on ion channels.
AB  - Neurotrophins (NTs) are [?AUTHOR] a family of structurally related, secreted
      proteins that regulate the survival, differentiation and maintenance of function
      of different populations of peripheral and central neurons.1,2 Among these, BDNF
      (brain-derived neurotrophic factor) has drawn considerable interest because both
      its synthesis and secretion are increased by physiological levels of activity,
      indicating a unique role of this neurotrophin in coupling neuronal activity to
      structural and functional properties of neuronal circuits. In addition to its
      classical neurotrophic effects, which are evident within hours or days and which
      usually result from changes in cellular gene expression, BDNF exerts acute
      effects on synaptic transmission and is involved in the induction of long-term
      potentiation. Many of these rapid effects of BDNF are mediated by its modulation
      of ion channel properties following TrkB-mediated activation of intracellular
      second messenger cascades and protein phosphorylation. However, recent reports
      have shown that BDNF not only acts as a modulator of ion channels, but can also
      directly and rapidly gate a Na(+) channel, thereby assigning BDNF the properties
      of a classical excitatory transmitter. Thus, BDNF, in addition its role as a
      potent neuromodulator, emerges as an excitatory transmitter-like substance which
      acutely controls resting membrane potential, neuronal excitability, synaptic
      transmission and participates in the induction of synaptic plasticity.

PMID- 15499581
TI  - The source(s) for new pancreatic beta cells in adult life.
AB  - The natural source for new pancreatic beta cells is an important issue both for
      understanding the pathogenesis of diabetes, and for possibly curing diabetes by
      increasing the number of beta cells. Dor et al. investigated beta-cell renewal
      and regeneration by genetic lineage analysis in mice during physiological growth
      and after partial pancreatectomy. The data conclusively showed that beta-cell
      replication was the only source for new beta cells without contributions from
      stem cells or other non-beta cells. This underlines the capacity for beta-cell
      self-renewal and casts doubt that other cell types are able to generate new beta
      cells in the intact pancreas.

PMID- 15499582
TI  - What the papers say: where is the somatic mutation that causes aging?
AB  - It has been proposed that somatic mutations make major contributions to aging.
      The first paper, based on a gene knock-in mouse, supports a contributory role for
      mutation in mtDNA in aging, but does not support a damaged-mtDNA-producing-more
      damaged-mtDNA hypothesis. The second paper indicates some GC-rich sequences in
      the nuclear DNA are more sensitive to oxidative damage than mtDNA. As a result,
      key genes involved in brain function and mitochondrial function are progressively
      inactivated with age. Failure in these nucleus-encoded mitochondrial genes may be
      a primary reason for mitochondrial failure in old age.

PMID- 15499583
TI  - Symmetry breaking in the left-right pattern and why vertebrates are better off.

PMID- 15499584
TI  - Exploring the multiple facets of the meiotic recombinase Dmc1.
AB  - Meiotic recombination in eukaryotic cells requires two homologs of E. coli RecA
      protein, Rad51 and Dmc1. Until recently, the role of Dmc1 in meiotic
      recombination was mostly attributed to genetic studies as purified Dmc1 was found
      to be a much weaker recombinase than Rad51 in the test tube. Now, Sehorn and
      colleagues1 have reported that, like Rad51, human Dmc1 is an efficient
      recombinase in vitro. Dmc1 forms helical nucleoprotein filaments--the signature
      of classical recombinases such as Rad51. These observations reveal a high level
      of similitude between the Dmc1 and the Rad51 family of recombination enzymes in
      higher eukaryotes.

PMID- 15499585
TI  - How consistent are expression chip platforms?
AB  - DNA arrays are now widely used in academia and industry, and expression profiling
      is recognised as a major tool for basic research as well as for drug development.
      It is also likely, in the near future, that DNA arrays will be used in clinical
      laboratories for diagnostic and prognostic purposes. Since several types of
      arrays are being used, the coherence of results obtained using these diverse
      platforms becomes an important issue: to what extent can data obtained in
      different laboratories and with different equipment be combined? Several recent
      papers address this issue and demonstrate that the expected agreement is not
      necessarily found. Consistent results can be obtained, but this requires careful
      identification of the genes assessed by the arrays, and scrupulous adherence to
      strict experimental procedures.

PMID- 15499586
TI  - The genetics of Drosophila transgenics.
AB  - In Drosophila, the genetic approach is still the method of choice for answering
      fundamental questions on cell biology, signal transduction, development,
      physiology and behavior. In this approach, a gene's function is ascertained by
      altering either the amount or quality of the gene product, and then observing the
      consequences. The genetic approach is itself polymorphous, encompassing new and
      more complex techniques that typically employ the growing collections of
      transgenes. The keystone of these modern Drosophila transgenic techniques has
      been the Gal4 binary system. Recently, several new techniques have modified this
      binary system to offer greater control over the timing, tissue specificity and
      magnitude of gene expression. Additionally, the advances in post-transcriptional
      gene silencing, or RNAi, have greatly expanded the ability to knockdown almost
      any gene's function. Regardless of the growing experimental intricacy, the
      application of these advances to modify gene activity still obeys the fundamental
      principles of genetic analysis. Several of these transgenic techniques, which
      offer more precise control over a gene's activity, will be reviewed here with a
      discussion on how they may be used for determining a gene's function.

PMID- 15499587
TI  - An intracellular actin motor in bacteria?
AB  - Actin performs structural as well as motor-like functions in eukaryotic cells.
      Orthologues of actin have also been identified in bacteria, where they perform an
      essential function during cell growth. Bacterial actins are implicated in the
      maintenance of rod-shaped cell morphology, and appear to form a cytoskeletal
      structure, localising as helical filaments underneath the cell membrane.
      Recently, a plasmid-borne actin orthologue has been shown to perform a mitotic
      like function during segregation of a plasmid, and chromosomally encoded actin
      proteins were found to play an important role in chromosome segregation. Based on
      the findings that actin filaments are dynamic structures in two bacterial
      species, we propose that actins perform motor functions rather than a purely
      structural role in bacteria. We suggest that an intracellular motor exists in
      bacteria that could be derived from an ancestral actin motor that was present in
      cells early in evolution.

PMID- 15499588
TI  - Is there a functional link between gene interdigitation and multi-species
      conservation of synteny blocks?
AB  - It is often overlooked that, in addition to the integrity of protein-coding
      sequences (PCSs), human health is crucially linked to the normal expression of
      genes by cis-regulatory sequences (CRSs). These CRSs often lie at some
      considerable distance from the PCSs whose expression they control and often
      within other genes. The resulting gene interdigitation can make long-range CRS
      identification and characterisation difficult. We propose that the need to
      conserve long-range CRSs in cis with their target PCSs through evolution, in
      combination with gene interdigitation and co-regulation of many genes by
      individual CRSs, has contributed to the persistence of conserved synteny blocks
      between diverse species. We further hypothesise that examination of the varying
      extents of synteny blocks between multiple species in combination with
      phylogenetic footprinting to find CRSs might provide important clues to the
      existence of crucial functional CRS-PCS linkages. Identifying CRS-PCS linkages
      crucial to human health will lead to a better understanding of how their
      disruption by CRS mutation or chromosome translocation might contribute to many
      distressing human diseases.

PMID- 15499589
TI  - In vitro culture of rat neuromicrovascular endothelial cells on polymeric
      scaffolds.
AB  - Polyphosphazenes are polymers possessing a skeleton composed of alternating
      phosphorous and nitrogen atoms, and two side-moieties linked to each phosphorous
      atom. Polyphosphazenes with amino acid esters as side-moieties are biocompatible
      and biodegradable polymers. Two polyphosphazenes, poly[bis(ethyl alanate)
      phosphazene] and poly[(ethyl phenylalanate)0.8(ethyl alanate)0.8(ethyl
      glycinate)0.4 phosphazene] (PPAGP) were synthesized, and processed to form small
      fibers. Their ability to support rat neuromicrovascular endothelial cell (EC)
      adhesion and growth has been studied, using poly(D,L-lactic acid) as reference
      compound. Scanning electron microscopy revealed that both poly[bis(ethyl alanate)
      phosphazene] and PPAGP fibers were thinner than poly(D,L-lactic acid) fibers, and
      possessed a more irregular and porous surface. All polymers increased EC
      adhesion, compared with polystyrene, but only polyphosphazenes were able to
      improve EC growth. The highest increase in EC proliferation was induced by PPAGP,
      which, as revealed by environmental scanning electron microscopy, was also able
      to induce ECs to arrange into tubular structures. The conclusion is drawn that
      PPAGP may provide the best scaffold for engineered blood vessels, because it
      promotes adhesion, growth, and organization of ECs into capillary-like
      structures.

PMID- 15499590
TI  - Floral zygomorphy, the recurring evolution of a successful trait.
AB  - The flowers of the primitive angiosperm plants were radially symmetrical
      (actinomorphic). Flowers with bilateral symmetry (zygomorphic) evolved in several
      clades independently as an adaptation to specialized methods of pollination and
      played an important role in the diversification of flowering plants. In the model
      species Antirrhinum majus (snapdragon), the related genes CYCLOIDEA (CYC) and
      DICHOTOMA (DICH) are key in the development of this trait. This raises the
      question of whether they played a role in the evolution of floral bilateral
      symmetry. To address this, the evolution of CYC in relation to the evolution of
      zygomorphy is being investigated. Phylogenetic and functional analyses of CYC
      like genes are being carried out in groups either closely related to Antirhinum
      or in families where zygomorphy evolved as an independent event. In addition, the
      origin of zygomorphy is being studied by comparing the function of CYC-like genes
      in species with zygomorphic flowers with their function in species with radially
      symmetrical flowers.

PMID- 15499591
TI  - Endogenous recovery of injured spinal cord: longitudinal in vivo magnetic
      resonance imaging.
AB  - Pathological changes were followed longitudinally with in vivo magnetic resonance
      imaging (MRI) and behavioral studies in experimental spinal cord injury (SCI).
      MRI-observed pathology was correlated with histology. On MRI, the cavitated
      regions of the injured cord were gradually filled with viable tissue between two
      and 8 weeks postinjury, and a concomitant improvement was observed in the
      neurobehavioral scores. By weeks 3-6, on MRI, the gray matter (GM) returned in
      the segments caudal, but not rostral, to the injury site. The corresponding
      histological sections revealed motor neurons as well as other nuclei in the gray
      matter immediately caudal to the epicenter, but not at the site of injury,
      suggesting neuronal recovery in perilesioned areas. The neuronal and neurological
      recovery appeared to occur about the same time as neovasculature that was
      reported on the contrast-enhanced MRI, suggesting a role for angiogenesis in
      recovery from SCI. The role of angiogenesis in neuronal recovery is further
      supported by the immunohistochemical observation of greater bromodeoxyuridine
      uptake by blood vessels near the lesion site compared with uninjured cords.

PMID- 15499592
TI  - Differential gene expression in neural stem cells and oligodendrocyte precursor
      cells: a cDNA microarray analysis.
AB  - The use of neural stem cells (NSCs) or their progeny oligodendrocyte precursor
      cells (OPCs) represents a promising repair strategy for many neurological
      disorders. However, the molecular events and biological features during the
      transition from NSCs to OPCs remain unclear. In the present study, we isolated
      NSCs from the embryonic rat forebrain and induced them into OPCs by using B104
      conditioned medium (B104CM) in vitro. We then employed cDNA array technology to
      compare changes in gene expression between the two cell populations. Among 1,176
      genes examined, 40 were differentially expressed, and some of them may be
      involved in OPC differentiation from NSCs. Our findings thus provide new insights
      into the molecular basis of differentiation of OPCs from NSCs.

PMID- 15499593
TI  - High mobility group box protein-1 inhibits microglial Abeta clearance and
      enhances Abeta neurotoxicity.
AB  - One pathogenic characteristic of Alzheimer's disease (AD) is the formation of
      extracellular senile plaques with accumulated microglia. According to the amyloid
      hypothesis, the increase or accumulation of amyloid-beta (Abeta) peptides in the
      brain parenchyma is the primary event that influences AD pathology. Although the
      role of microglia in AD pathology has not been clarified, their involvement in
      Abeta clearance has been noted. High mobility group box protein-1 (HMGB1) is an
      abundant nonhistone chromosomal protein. We reported recently that HMGB1 was
      associated with senile plaques and the total protein level significantly
      increased in AD brain. In this study, diffuse HMGB1 immunoreactivity was observed
      around dying neurons in the kainic acid- and Abeta1-42 (Abeta42)-injected rat
      hippocampi. HMGB1 also colocalized with Abeta in the Abeta42-injected rats but
      not in transgenic mice, which show massive Abeta production without neuronal loss
      in their brains. Furthermore, coinjection of HMGB1 delayed the clearance of
      Abeta42 and accelerated neurodegeneration in Abeta42-injected rats. These results
      suggest that HMGB1 released from dying neurons may inhibit microglial Abeta42
      clearance and enhance the neurotoxicity of Abeta42. HMGB1 may thus be another
      target in the investigation of a therapeutic strategy for AD.

PMID- 15499594
TI  - Prenatal stress causes gender-dependent neuronal loss and oxidative stress in rat
      hippocampus.
AB  - Our purpose was to investigate the effects of prenatal stress on neuronal changes
      in the hippocampus and the possible involvement of oxidative stress in female and
      male rats. Female and male offspring (1-month-old), whose dams were restrained in
      middle or later pregnant stage (MS or LS), were studied to observe changes in the
      number of hippocampal neurons and the expression of neuronal nitric oxide
      synthase (nNOS) in the hippocampus. Both MS and LS induced an increase in the
      number of nNOS-positive expression in female and male offspring in the
      hippocampus; however, both MS and LS caused a significant decrease in the number
      of hippocampal neurons in the female, but not in the male offspring. In addition,
      significant increases in calcium content and oxidant generation were induced by
      LS in the hippocampal CA3 region in female rats. These data suggest that prenatal
      stress can cause oxidative stress and consequent damage to neurons, leading to
      neuronal loss in the brain of offspring during development.

PMID- 15499596
TI  - Recall and detection rates in screening mammography.

PMID- 15499597
TI  - Clinical significance of intramural extension of rectal cancer to the sphincter
      muscles.

PMID- 15499598
TI  - Immunohistological evaluation of single small hepatocellular carcinoma with
      negative staining of monoclonal antibody Hepatocyte Paraffin 1.
AB  - BACKGROUND AND OBJECTIVES: The sensitivity and specificity of the monoclonal
      antibody Hepatocyte Paraffin 1 (Hep Par 1) for hepatocellular carcinoma (HCC) are
      very high, and the usefulness for differential diagnosis of hepatic tumors has
      been reported. However, there are some cases of HCC with negative staining for
      Hep Par 1. We examined the histopathological features of HCC with negative
      staining for Hep Par 1. METHODS: We examined 69 samples of single nodular HCC
      less than 2 cm in greatest dimension, resected from 1985 to 1994 in our hospital,
      with immunohistological staining for Hep Par 1, cytokeratin 19 (CK 19), MUC-1
      glycoprotein (MUC-1), and epithelial membrane antigen (EMA). RESULTS: Hep Par 1
      staining was positive in 64 cases (93%) and negative in 5 cases (7%). With regard
      to the histological structure, 3 of the 5 negative cases were scirrhous HCC. With
      regard to the grade of histological differentiation, 2 cases were poorly
      differentiated HCC, 3 cases were moderately differentiated HCC, and no well
      differentiated HCC was found in the negative cases. CK 19, MUC-1, and EMA
      staining were negative in all cases. CONCLUSIONS: It is necessary to recognize
      the existence of Hep Par 1 negative HCC, in particular scirrhous HCC. This may be
      due to a different mechanism in the earlier stage of hepatocarcinogenesis.

PMID- 15499599
TI  - Elevated expression of cyclooxygenase-2 in breast cancer and ductal carcinoma in
      situ has no correlation with established prognostic markers.
AB  - BACKGROUND AND OBJECTIVES: Elevated expression of cyclooxygenase-2 (COX-2) has
      been established to be a feature of breast cancer. There has been inconsistency
      in the literature regarding the precise significance of this-some studies have
      found no clinicopathological relevance at all, whilst others have concluded COX-2
      expression is an important biomarker in invasive disease and pre-cancerous
      lesions, correlating with poor prognostic features. We studied COX-2 expression
      in invasive ductal cancer (IDC) specimens and ductal carcinoma in situ (DCIS) in
      order to clarify these issues. METHOD: Archival specimens of IDC and DCIS (n =
      39) were stained with a polyclonal antibody to COX-2. Results were correlated
      with recognised clinicopathological parameters. RESULTS: COX-2 expression
      occurred in 36.7% of IDCs and 54.5% of DCIS lesions. There was no correlation
      between increased expression and any clinicopathological features. COX-2
      expression did not occur in adjacent non-cancerous tissue (ANCT). CONCLUSION: We
      have confirmed that COX-2 expression does occur in invasive cancers, in DCIS, and
      is not associated with established prognostic markers. The presence of COX-2
      expression in DCIS and invasive cancers has positive implications for the future
      prevention and treatment of breast cancer with COX-2 inhibitors. A large
      proportion of tumours are, however, COX-2 negative and may be poor candidates for
      COX-2 suppression.

PMID- 15499600
TI  - Tuech et al.: Detection of occult liver metastases in colorectal cancer by
      measurement of biliary carcinoembryonic antigen concentration: a prospective
      study.

PMID- 15499601
TI  - Randomised phase 2 trial of SIR-Spheres plus fluorouracil/leucovorin chemotherapy
      versus fluorouracil/leucovorin chemotherapy alone in advanced colorectal cancer.
AB  - PURPOSE: Selective internal radiation therapy (SIRT) with SIR-Spheres(R) is a new
      technique for selectively targeting high doses of radiation to tumours within the
      liver. The primary objectives of this randomised trial were to compare the
      response rate, time to progressive disease (PD), and toxicity of a regimen of
      systemic fluorouracil/leucovorin chemotherapy versus the same chemotherapy plus a
      single administration of SIR-Spheres in patients with advanced colorectal liver
      metastases. The trial was designed to presage a larger trial that would have
      survival as the primary outcome. PATIENTS AND METHODS: Twenty-one patients with
      previously untreated advanced colorectal liver metastases, with or without
      extrahepatic metastases, were randomised into the study. RESULTS: Using RECIST
      criteria, the response rate for 11 patients receiving the combination treatment
      was significantly greater than for 10 patients receiving chemotherapy alone
      (First Integrated Response; 10 PR, 1 SD vs. 0 PR, 6 SD, 4 PD, P < 0.001 and Best
      Confirmed Response; 8 PR, 3 SD vs. 0 PR, 6 SD, 4 PD P < 0.001). The time to PD
      was greater for patients receiving the combination treatment (18.6 months vs. 3.6
      months, P < 0.0005). Median survival was significantly longer for patients
      receiving the combination treatment (29.4 months vs. 12.8 months, P = 0.02). One
      patient in the combination arm died from chemotherapy induced neutropenic sepsis
      after the fourth chemotherapy cycle. There were more Grade 3 and 4 toxicity
      events in patients receiving the combination treatment. There was no difference
      in quality-of-life over a 3 month period between the two treatments when rated by
      patients (P = 0.96) or physicians (P = 0.98). CONCLUSIONS: This small phase 2
      randomised trial demonstrated that the addition of a single administration of SIR
      Spheres to a regimen of systemic fluorouracil/leucovorin chemotherapy
      significantly increased both treatment related response, time to PD, and survival
      with acceptable toxicity. The combination of SIR-Spheres plus systemic
      chemotherapy is now the subject of ongoing trials to further define patient
      benefit.

PMID- 15499602
TI  - High-mobility group protein 1(Y): metastasis-associated or metastasis-inducing?
AB  - Metastasis is the major cause of mortality and morbidity for patients with
      cancer. The high-mobility group protein 1(Y) [HMG-1(Y)] has a role in the
      transcription of many genes involved at different steps in the metastatic cascade
      and has been linked with cancer in human and animal models. This may represent a
      potential therapeutic target for patients. The following review summarizes and
      critically appraises the evidence for the role of HMG-1(Y) in metastasis.

PMID- 15499604
TI  - Postoperative pulmonary complications are associated with worse short- and long
      term outcomes after extended esophagectomy.
AB  - BACKGROUND: Risk analysis of pulmonary complications after extended esophagectomy
      with three-field lymph node dissection (3FLND) has been little reported in the
      literature. METHODS: Risk factors of developing postoperative pneumonia after
      extended esophagectomy and its effects on in-hospital death and overall long-term
      survival were compared between 38 patients who developed pneumonia and 80
      patients who did not. RESULTS: Eight patients died of postoperative complications
      during the hospital stay after esophagectomy. Seven of those 8 patients developed
      pneumonia, whereas 31 patients of 110 patients who were discharged from the
      hospital developed pneumonia (P < 0.01). Pneumonia occurred more frequently in
      elderly patients (P < 0.01), in heavy smokers (P < 0.05), in patients with
      preoperative pulmonary obstructive dysfunction (P < 0.05), and in patients who
      received 3 U or more perioperative blood transfusion (P < 0.05). Five-year
      overall survival rate (26.7%) of 38 patients who developed pneumonia was
      significantly worse than 53.4% who did not develop pneumonia (P < 0.01).
      Multivariate analysis of prognostic factors for overall survival showed that
      pathological tumor stage (hazard ratio 5.380, P < 0.01) and pneumonia (hazard
      ratio 2.369, P < 0.01) were independent risk factors. Postoperative pneumonia is
      correlated with in-hospital death and poorer long-term survival after extended
      esophagectomy with 3FLND. CONCLUSIONS: Elderly patients with a history of heavy
      smoking and poor pulmonary function should be regarded as a high-risk group of
      patients for developing pneumonia and very careful selection is required before
      subjecting such patients to extended esophagectomy.

PMID- 15499605
TI  - Selective alterations of gene expression in mice induced by MPTP.
AB  - 1-methyl-4-phenyl-1,2,4,6,-tetrahydropyridine (MPTP) is a selective neurotoxin
      that produces striatal dopamine depletion resulting in parkinsonism like symptoms
      in humans and is, therefore, used to generate animal models for Parkinson's
      disease (PD). In this study, C57BL/6N mice were treated with MPTP acutely (3x20
      mg/kg, 2-hour interval, one day injection). Mice were then sacrificed 24 hours
      after the last injection and brain tissue was collected for analysis. Significant
      decrease of striatal dopamine (DA) and the metabolites (DOPAC, HVA) was observed
      after MPTP treatment. MPTP also reduced protein expression of tyrosine
      hydroxylase (TH) in the striatum. Real time RT-PCR was used to examine selective
      genes of the dopaminergic system in the substantia nigra. Our data demonstrated
      that MPTP significantly decreased gene expression of TH, dopamine transporter
      (DAT), and vesicle monoamine transporter (VMAT), coinciding with the pattern of
      dopamine concentration changes and protein expression after MPTP treatment.
      Although a significant decrease of DA metabolites was observed in striatum, there
      was no change in the expression of monoamine oxidases (MAO-A, MAO-B) or catechol
      O-methyltransferase (COMT), indicating that these changes might be simply a
      consequence of reduced monoamine levels. In addition, gene expression of alpha
      synuclein was also decreased with MPTP treatment, but there was no change in beta
      synuclein and parkin. This is the first study using real-time PCR to indicate
      that MPTP selectively alters gene expression and provides information for
      clinical studies in PD. Future studies will focus on gene expression of other
      pathways that may be affected by MPTP treatment and investigation of gene
      expression in specific cell types in vivo using LCM technology.

PMID- 15499606
TI  - Does overweight impact on the prognosis of patients with renal cell carcinoma? A
      single center experience of 683 patients.
AB  - BACKGROUND AND OBJECTIVES: An increased incidence of renal cell carcinoma (RCC)
      in obese patients has been reported by several authors. We investigated the
      association of body mass index (BMI) with prognosis of patients with RCC.
      METHODS: From January 1994 to December 2000, 693 operations for RCC in 683
      consecutive patients were performed at our institution. Patients' BMI at
      operation was evaluated, overall, tumor-specific and progression-free survival
      was investigated using the Kaplan-Meier method, for multivariate analysis the Cox
      regression model was used. RESULTS: Four hundred seventeen patients were males,
      266 females. Mean age was 62 years (range 16-88). BMI was available in 609
      (89.2%). 371/609 (60.9%) of patients exhibited a BMI greater than 25. After a
      mean follow-up of 41.5 months, 86 (12.6%) patients died from metastatic RCC, and
      29 (4.3%) were alive with metastatic disease. A significant advantage regarding
      overall (P = 0.015) and progression-free (0.017) but not tumor-specific survival
      (P = 0.057) was found for patients with a BMI of more than 25 compared to normal
      weight patients. In multivariate analysis, BMI showed no significant association
      with tumor-specific survival. CONCLUSIONS: Patients with a BMI of more than 25
      had a better outcome compared to patients with normal weight in univariate
      analysis but not multivariate analysis.

PMID- 15499607
TI  - Intermittent morphine treatment induces a long-lasting increase in cholinergic
      modulation of GABAergic synapses in nucleus accumbens of adult rats.
AB  - Repeated exposure to drugs of abuse causes persistent behavioral sensitization
      and associated adaptations of striatal neurotransmission, which is thought to
      play an important role in certain aspects of drug addiction. Microdialysis and
      neurochemical studies suggest that intermittent morphine treatment may lead to a
      long-term increase in both ACh and dopaminergic neurotransmission in the nucleus
      accumbens (NAc). This implies that both cholinergic modulation of GABA synapses
      and their sensitivity to dopaminergic transmission might be changed, ultimately
      leading to a modified NAc output. Here we investigate to what extent cholinergic
      modulation and sensitivity to amphetamine, causing endogenous dopamine efflux, of
      GABAergic transmission in the nucleus accumbens are affected 3 weeks after a
      period of daily morphine injections in adult rats. To this end, we recorded
      medium spiny neurons using whole cell voltage clamp and monitored the frequency
      and amplitude of spontaneous GABAergic synaptic currents. We observed that the
      effect of nicotine on the frequency of spontaneous inhibitory postsynaptic
      currents (sIPSCs) was suppressed in rats pretreated with morphine, whereas the
      effects of mecamylamine and tetrodotoxin (TTX) were increased. These results
      indicate that the probability of GABA release was increased and that this effect
      resulted from an upregulation of the endogenous activation of presynaptic
      nicotinic receptors. In addition, we observed an increased sensitivity to in
      vitro application of amphetamine. This suggests that the long-term increase in
      dopaminergic transmission caused by the morphine treatment affects GABA synapses
      in the NAc. Hence, there may be two parallel synaptic mechanisms by which drugs
      of abuse may affect processing and integration of NAc inputs.

PMID- 15499608
TI  - Distinct modulatory roles of sigma receptor subtypes on glutamatergic responses
      in the dorsal hippocampus.
AB  - Sigma ligands have been previously shown to modulate the N-methyl-D-aspartate
      (NMDA) response in the dorsal hippocampus, such that low doses of sigma agonists
      dose-dependently potentiate the response. Recent studies with the sigma ligand 4
      IBP found it to act differently from the sigma ligands (+)-pentazocine and DTG in
      the modulation of 5-HT firing activity in the dorsal raphe nucleus (DRN), as its
      effects were not blocked by the sigma antagonists which reversed those of (+)
      pentazocine or DTG. Thus, this study set out to characterize 4-IBP's action at
      sigma receptors using the hippocampal paradigm of sigma ligand activity.
      Interestingly, we found that in 50% of the neurons recorded, 4-IBP (20 microg/kg
      i.v.) produced a potentiation of both NMDA- and quisqualate (QUIS)-induced
      responses. In the other 50% of neurons, 4-IBP produced an attenuation of both
      QUIS and NMDA responses. The sigma1 antagonist NE-100 blocked the reduction
      induced by 4-IBP, while the nonselective sigma antagonist haloperidol blocked all
      responses induced by 4-IBP. These data suggest that, in this model, 4-IBP may be
      acting as an agonist or inverse agonist of sigma receptors. Furthermore, the
      initial responses to NMDA and QUIS were higher in the group in which 4-IBP
      induced an attenuation of the firing activity. This suggests a modulatory role
      for 4-IBP on glutamatergic neurotransmission in the hippocampus, which appears to
      involve two distinct pathways, mediated by different sigma1 receptor subtypes, an
      NE-100 and haloperidol-sensitive sigma1 receptor, and an NE-100-insensitive,
      haloperidol-sensitive sigma1 receptor. This modulatory role has implications for
      disorders that involve glutamatergic transmission in the hippocampus.

PMID- 15499609
TI  - Dose and behavioral context dependent inhibition of movement and basal ganglia
      neural activity by Delta-9-tetrahydrocannabinol during spontaneous and treadmill
      locomotion tasks in rats.
AB  - The effects of Delta-9-tetrahydrocannabinole (Delta-9-THC) on locomotor
      activities and related basal ganglia neural responses were investigated in rats.
      A multiple-channel, single unit recording method was used to record neuronal
      activity in the dorsal lateral striatum, the globus pallidus, the subthalamic
      nucleus, and the substantia nigra pars reticulata simultaneously during
      spontaneous movement and treadmill locomotion. Delta-9-THC treatment (0.05-2.0
      mg/kg, i.p.) dose-dependently decreased spontaneous motor activity and altered
      walking patterns in treadmill locomotion in that stance time was increased and
      step number was decreased. In parallel with the behavioral effects, Delta-9-THC
      treatment inhibited neural activity across all four basal ganglia areas recorded
      during both motor tests. Further, this inhibition of basal ganglia neural
      activity was behavioral context-dependent. Greater inhibition was found during
      resting than during walking periods in the treadmill locomotion test. Delta-9-THC
      treatment also changed firing patterns in the striatum and globus pallidus. More
      neurons in these regions discharged in an oscillatory pattern during treadmill
      walking with Delta-9-THC, and the oscillatory frequency was similar to that of
      the step cycle. Synchronized firing patterns were found in few basal ganglia
      neurons in the control condition (approximately 1%). Synchronized firing patterns
      increased during the treadmill resting phase after Delta-9-THC treatment, but
      still represented a very small proportion of the total neural population (1.9%).
      The drug treatment did not change neural responses to the tone cue proceeding
      treadmill locomotion. This study demonstrates dose-dependent inhibitory effects
      of cannabinoid injection on motor activity. This effect may be related to the
      behavioral context-dependent inhibition observed in the basal ganglia system
      where CB1 receptors are densely distributed.

PMID- 15499610
TI  - Behavioral and anatomical effects of quinolinic acid in the striatum of the
      hemiparkinsonian rat.
AB  - Parkinson's disease (PD), a hypokinetic disorder, and Huntington's disease (HD),
      a hyperkinetic disorder, share the fact that in the motor pathways the
      dysfunction starts in the striatum. In PD the projection neurons are overactive
      due to decreased inhibitory regulation by lost dopamine afferents, while in HD
      the output from the striatum is insufficient due to loss of projection neurons.
      This study aimed to determine whether the introduction of a mild HD condition in
      the PD striatum can counter the hypokinetic condition. The experiment was carried
      out in the 6-OHDA rat model for PD in which amphetamine, 5 mg/kg, evokes an
      asymmetric rotation response toward the side of the 6-OHDA lesion (ipsilateral
      rotation). The response to amphetamine in this study was fractionated into
      multiple components and measured automatically. After baseline measurements, the
      subjects were divided into four groups. Group I was unilaterally sham-lesioned in
      medial, central, and lateral striatum. Group II was injected quinolinic acid (QA)
      20 nM in medial, central, and lateral striatum. Group III was injected QA 60 nM
      in central striatum. Group IV was injected QA 120 nM in central striatum. The
      effects of QA were measured weekly. The sham lesions in Group I had no effects.
      In Group II, ipsilateral rotation was reduced and replaced by oral stereotypy, a
      competitive behavior. In Group III, ipsilateral rotation decreased, but to a
      lesser degree than in Group II. In Group IV, QA had no effects. Histological
      findings show a unilateral loss of tyrosine immunoreactive (TH) neurons in
      substantia nigra and of fibers in striatum in all subjects. In addition, in Group
      II the striatum was atrophied. These findings suggest that the shift in Group II
      from ipsilateral rotation to oral stereotypy after QA was due to reduced striatal
      output caused by a loss of projection neurons, a loss insufficient to induce HD
      symptoms, but sufficient to counter the PD condition.

PMID- 15499611
TI  - Low doses of beta-carotene and lutein inhibit AOM-induced rat colonic ACF
      formation but high doses augment ACF incidence.
AB  - Epidemiological studies suggest that carotenoids such as beta-carotene and lutein
      play an important role in reducing the risk for several cancers. However, in
      colon cancer there is ambiguity with regard to the role of these compounds in
      that both preventive effects and tumor promotion have been observed. In the
      present study we observed that male F344 rats were able to tolerate up to 2,500
      ppm of beta-carotene as well as of lutein. We have then assessed the
      chemopreventive efficacy of beta-carotene and lutein at dose levels of
      approximately 4 and 8% of the 2,500 ppm tolerated dose (TD) and also
      approximately 40 and 80% of the TD on azoxymethane (AOM)-induced colon
      carcinogenesis, using aberrant crypt foci (ACF) as a surrogate biomarker for
      colon cancer. Throughout the experiments, 5-week-old male F344 rats were fed the
      control diet (modified AIN-76A) or experimental diets containing 100 or 200 ppm
      (approximately 4 or 8% of the 2,500 ppm TD), or 1,000 or 2,000 ppm (
      approximately 40 or 80% of the 2,500 ppm TD) of beta-carotene and lutein (n=10
      rats/group). After 2 weeks on the experimental or control diets, all animals were
      injected with AOM (15 mg/kg body wt., once weekly for 2 weeks). At 14 weeks of
      age, all rats were killed, and their colons were evaluated for ACF.
      Administration of 100 or 200 ppm of beta-carotene inhibited AOM-induced total
      colonic ACF formation by 24% (p<0.01) and 36% (p<0.001), respectively, whereas
      lutein at 200 ppm produced a 27% inhibition (p<0.01) yet had no significant
      effect at the 100 ppm dose level. Surprisingly, administration of 1,000 or 2,000
      ppm of beta-carotene and lutein increased colonic ACF formation in a dose
      dependent manner, i.e., to 124% and 144% for the former and 110% and 159% for the
      latter. These results clearly suggest that further studies are warranted to
      determine whether the increase in ACF incidence by high doses of beta-carotene
      and lutein will also lead to an increase in tumor outcome. Taken together these
      data indicate that the chemopreventive activity of beta-carotene and lutein
      against colon carcinogenesis depends on the dose level.

PMID- 15499612
TI  - In vivo efficacy of STI571 in xenografted human small cell lung cancer alone or
      combined with chemotherapy.
AB  - STI571, or imatinib, selectively inhibits BCR/ABL, PDGFR and c-kit kinase
      activity. It has been reported that a large proportion of small cell lung cancer
      (SCLC) cell lines and tumors express c-kit and that STI571 inhibits tumor cell
      growth. We therefore investigated the therapeutic efficacy of STI571, alone or
      combined with chemotherapy, in human SCLC cells or tumors xenografted into nude
      mice. The level of c-kit mRNA expression was variable in SCLC tumors (positive
      for 2 of 4 xenografts), and c-kit protein was not detected by
      immunohistochemistry. On the 4 xenografted tumors, PDGFRalpha and PDGFRbeta were
      not detected by immunohistochemistry. STI571 induced inhibition of proliferation
      of the SCLC6 cell line without inducing apoptosis; in contrast, in combination
      with etoposide or topotecan, the growth inhibition of SCLC6 cells induced by
      STI571 was increased, with apoptotic DNA fragmentation. Four human SCLC
      xenografts (SCLC6, SCLC61, SCLC74 and SCLC108) were transplanted into mice. After
      intraperitoneal injection of STI571, we observed 80%, 40% and 78% growth
      inhibition of SCLC6, SCLC61 and SCLC108 tumors, respectively, without any
      significant inhibition of SCLC74 tumor growth. In mice bearing responsive SCLC
      tumors, we observed an increase of growth inhibition induced by chemotherapy
      (etoposide + ifosfamide or topotecan) by concomitant and continuous
      administration of STI571, associated with an increase of toxic deaths. In SCLC6
      bearing mice receiving sequential treatments, we observed a reduction of toxic
      deaths but a decrease of synergistic antitumor efficacy. In conclusion, the
      efficacy of STI571 alone in SCLC xenografted tumors was variable and did not
      depend on c-kit expression. Moreover, a significant increase of chemotherapy
      induced growth inhibition was obtained by concomitant administration of STI571
      that should be carefully investigated in SCLC patients.

PMID- 15499613
TI  - Tyrosine phosphorylation of PYK2 mediates heregulin-induced glioma invasion:
      novel heregulin/HER3-stimulated signaling pathway in glioma.
AB  - Receptor tyrosine kinases of the EGFR family transmit extracellular signals that
      control diverse cellular functions such as proliferation, differentiation and
      survival. Signaling function of a member of this family, HER3, is believed to be
      impaired due to deviations in its kinase consensus motifs. Here we address the
      functional role and signaling mechanisms of HER3. HER3 preferentially forms
      heterodimers with HER2 inducing the most potent mitogenic signal among EGFR
      family members. Our data show that in a glioma-derived cell line the cytoplasmic
      tyrosine kinase PYK2 is constitutively associated with HER3 and that stimulation
      with Heregulin results in PYK2 tyrosine phosphorylation. HER3, but not HER2,
      mediates the phosphorylation of the C-terminal region of PYK2 to promote a
      mitogenic response through activation of the MAPK pathway. A central role of PYK2
      in signaling downstream of HER3 is substantiated by the demonstration that
      expression of a dominant-negative PYK2-KM construct abrogates the Heregulin
      induced MAPK activity and inhibits the invasive potential of glioma cells. These
      results suggest a novel Heregulin/HER3-stimulated signaling pathway in
      glioblastoma-derived cell lines that involves phosphorylation of PYK2 and
      mediates invasiveness of glioma cells.

PMID- 15499614
TI  - Breast cancer risk associated with estrogen receptor expression in epithelial
      hyperplasia lacking atypia and adjacent lobular units.
AB  - Estrogen is associated with many epidemiologic risk factors for invasive breast
      cancer. Cells that express estrogen receptors (ERs) in epithelial hyperplasia
      lacking atypia (EHLA) may influence breast cancer progression. We conducted a
      nested case-control study of 268 women with biopsy-confirmed EHLA to determine
      whether immunohistochemical expression of ERalpha in EHLA affects subsequent
      breast cancer risk. Study subjects could not have a prior or current history of
      breast cancer or atypical hyperplasia. Immunohistochemical stains in individual
      lesions and adjacent normal lobules were considered positive if >or= 10% of
      epithelial cells stained for ERalpha. The risk of invasive breast cancer in EHLA
      patients with ERalpha-positive normal lobules was twice that of other EHLA
      patients (95% CI = 1.0-3.8). This risk was not affected by the ERalpha status of
      EHLA lesions. ERalpha expression in adjacent normal lobules increases the
      moderate breast cancer risk previously associated with EHLA.

PMID- 15499615
TI  - Microvesicles derived from activated platelets induce metastasis and angiogenesis
      in lung cancer.
AB  - The role of platelets in tumor progression and metastasis has been recognized but
      the mechanism of their action remains unclear. Five human lung cancer cell lines
      (A549, CRL 2066, CRL 2062, HTB 183, HTB 177) and a murine Lewis lung carcinoma
      (LCC) cell line (for an in vivo model of metastasis) were used to investigate how
      platelet-derived microvesicles (PMV), which are circular fragments shed from the
      surface membranes of activated platelets, and exosomes released from platelet
      alpha-granules, could contribute to metastatic spread. We found that PMV
      transferred the platelet-derived integrin CD41 to most of the lung cancer cell
      lines tested and stimulated the phosphorylation of mitogen-activated protein
      kinase p42/44 and serine/threonine kinase as well as the expression of membrane
      type 1-matrix metalloproteinase (MT1-MMP). PMV chemoattracted 4 of the 5 cell
      lines, with the highly metastatic A549 cells exhibiting the strongest response.
      In A549 cells, PMV were shown to stimulate proliferation, upregulate cyclin D2
      expression and increase trans-Matrigel chemoinvasion. Furthermore, in these
      cells, PMV stimulated mRNA expression for angiogenic factors such as MMP-9,
      vascular endothelial growth factor, interleukin-8 and hepatocyte growth factor,
      as well as adhesion to fibrinogen and human umbilical vein endothelial cells.
      Intravenous injection of murine PMV-covered LLC cells into syngeneic mice
      resulted in significantly more metastatic foci in their lungs and LLC cells in
      bone marrow than in control animals injected with LCC cells not covered with PMV.
      Based on these findings, we suggest that PMV play an important role in tumor
      progression/metastasis and angiogenesis in lung cancer.

PMID- 15499616
TI  - Investigation of human brain tumors for the presence of polyomavirus genome
      sequences by two independent laboratories.
AB  - JC virus (JCV), BK virus (BKV) and simian virus 40 (SV40) may be associated with
      human brain tumors. These polyomaviruses have been shown to induce brain tumors
      in experimentally infected animals. Several studies have found polyomavirus
      genomic sequences in human brain tumor tissues by using polymerase chain reaction
      (PCR), while others have not. Inconsistencies in previous findings may be due in
      part to small sample sizes and differences in underlying patient populations,
      laboratory techniques and quality control measures. To assess the role of
      polyomaviruses in human brain tumors and address inconsistencies of previous
      reports, we investigated the prevalence of viral sequences in a series of 225
      brain tumor tissue specimens in 2 independent laboratories. PCR followed by
      Southern hybridization was performed at the National Institute of Neurological
      Disorders and Stroke (NINDS). Real-time quantitative PCR was performed on the
      same tissues at Johns Hopkins University (JHU). Only those tumors with
      amplifiable DNA were tested further for polyomavirus sequences. Positive and
      negative control tissues were included, and all specimens were masked.
      Amplifiable DNA was detected in 225/225 (100%) tumors at NINDS, 9 (4%) of which
      contained polyomavirus sequences (3 JCV-positive, 3 BKV-positive and 3 SV40
      positive). The JHU laboratory amplified DNA from 165/225 (73%) tumors, of which 1
      tumor tested positive (for SV40). No tumors tested positive in both laboratories.
      Results for masked quality control tissues were concordant between laboratories.
      Nucleotide sequences for JCV, BKV and SV40 are rarely present in a large series
      of adult and pediatric brain tumors.

PMID- 15499617
TI  - Dosing and scheduling influence the antitumor efficacy of a phosphinic peptide
      inhibitor of matrix metalloproteinases.
AB  - The in vivo disposition and antitumor efficacy of a newly developed phosphinic
      matrix metalloproteinase inhibitor (RXP03) were examined. RXP03 potently inhibits
      MMP-11, MMP-8 and MMP-13, but not MMP-1 and MMP-7. Twenty-four hours after i.p.
      injection into mice, most of the RXP03 was recovered intact in plasma, feces
      (biliary excretion) and tumor tissue. Pharmacokinetic parameters indicated that,
      after an i.p. dose of 100 microg/day, the plasma concentration of RXP03 over 24
      hr remained higher than the Ki values determined for MMP-11, MMP-8 and MMP-13.
      Efficacy of RXP03 on the growth of primary tumors induced by s.c. injection of
      C(26) colon carcinoma cells in mice was observed to depend both on RXP03 doses
      and treatment schedules. Tumor volumes in mice treated for 18 days with 50, 100
      and 150 microg/day of RXP03 were decreased compared with control tumor volumes,
      100 microg/day being the most effective dose. Treatment at higher dose (600
      microg/day) did not significantly reduce the tumor size as compared to control.
      Short treatments with RXP03 100 microg/day, 3 to 7 days after C(26) inoculation,
      were more effective on tumor growth than continuous treatment over 18 days.
      Strikingly, RXP03 treatment started 6 days after the C(26) injection and
      continued until day 18 led to stimulation of tumor growth, as compared to
      control. These paradoxical effects, depending on the RXP03 treatment schedule,
      underline the need to define carefully the spatiotemporal function of each MMP at
      various stages of tumor growth to achieve optimal therapeutic effects by MMP
      inhibitor treatment.

PMID- 15499618
TI  - Novel markers for poor prognosis in head and neck cancer.
AB  - Head and neck cancer (HNSCC) is one of the most distressing human cancers,
      causing pain and affecting the basic survival functions of breathing and
      swallowing. Mortality rates have not changed despite recent advances in
      radiotherapy and surgical treatment. We have compared the expression of over
      13,000 unique genes in 7 cases of matched HNSCC and normal oral mucosa. Of the
      1,260 genes that showed statistically significant differences in expression
      between normal and tumor tissue at the mRNA level, the three top ranking of the
      top 5% were selected for further analysis by immunohistochemistry on paraffin
      sections, along with the tumor suppressor genes p16 and p53, in a total of 62
      patients including 55 for whom >4-year clinical data was available. Using
      univariate and multivariate survival analysis, we identified SPARC/osteonectin as
      a powerful independent prognostic marker for short disease-free interval (DFI) (p
      < 0.002) and poor overall survival (OS) (p = 0.018) of HNSCC patients. In
      combination with other ECM proteins found in our analysis, PAI-1 and uPA, the
      association with DFI and OS became even more significant (p < 0.001). Our study
      represents the first instance of SPARC as an independent prognostic marker in
      HNSCC.

PMID- 15499619
TI  - Red meat consumption and risk of cancers of the proximal colon, distal colon and
      rectum: the Swedish Mammography Cohort.
AB  - Although there is considerable evidence that high consumption of red meat may
      increase the risk of colorectal cancer, data by subsite within the colon are
      sparse. The objective of our study was to prospectively examine whether the
      association of red meat consumption with cancer risk varies by subsite within the
      large bowel. We analyzed data from the Swedish Mammography Cohort of 61,433 women
      aged 40-75 years and free from diagnosed cancer at baseline in 1987-1990. Diet
      was assessed at baseline using a self-administered food-frequency questionnaire.
      Over a mean follow-up of 13.9 years, we identified 234 proximal colon cancers,
      155 distal colon cancers and 230 rectal cancers. We observed a significant
      positive association between red meat consumption and risk of distal colon cancer
      (p for trend = 0.001) but not of cancers of the proximal colon (p for trend =
      0.95) or rectum (p for trend = 0.32). The multivariate rate ratio for women who
      consumed 94 or more g/day of red meat compared to those who consumed less than 50
      g/day was 2.22 (95% confidence interval [CI] 1.34-3.68) for distal colon, 1.03
      (95% CI 0.67-1.60) for proximal colon and 1.28 (95% CI 0.83-1.98) for rectum.
      Although there was no association between consumption of fish and risk of cancer
      at any subsite, poultry consumption was weakly inversely related to risk of total
      colorectal cancer (p for trend = 0.04). These findings suggest that high
      consumption of red meat may substantially increase the risk of distal colon
      cancer. Future investigations on red meat and colorectal cancer risk should
      consider cancer subsites separately.

PMID- 15499620
TI  - Folate intake and colorectal cancer risk: a meta-analytical approach.
AB  - Adequate consumption of folate may reduce the risk of colorectal cancer. We
      performed a meta-analysis of 7 cohort and 9 case-control studies that examined
      the association between folate consumption and colorectal cancer risk. In cohort
      studies, the association between folate consumption and colorectal cancer risk
      was stronger for dietary folate (folate from foods alone; relative risk for high
      vs. low intake = 0.75; 95% CI = 0.64-0.89) than for total folate (folate from
      foods and supplements; relative risk for high vs. low intake = 0.95; 95% CI =
      0.81-1.11) and there was no significant heterogeneity between studies. There was
      significant heterogeneity between case-control studies. These results offer some
      support for the hypothesis that folate has a small protective effect against
      colorectal cancer but confounding by other dietary factors cannot be ruled out.

PMID- 15499621
TI  - Influence of GSTM1, GSTT1, GSTP1 and NAT2 genotypes on the p53 mutational
      spectrum in bladder tumours.
AB  - Genetic polymorphisms affecting expression or activity of the corresponding
      enzymes can influence the risk of acquiring gene mutations and various cancers.
      We have studied 327 bladder cancer patients with regard to the functionally
      related polymorphisms of GSTM1, GSTT1, GSTP1 and NAT2 and analysed the p53
      mutational status of their tumours. Fifty p53 mutations, 26% transversions and
      74% transitions, were detected in 44 patients. P53 mutation frequency was
      significantly higher in higher-grade tumours than in low-grade tumours (OR =
      2.09, 95% CI 1.44-3.02, adjusted for age and sex). Also, a significant
      association was found between tumour stage (Tis and T2+ vs. Ta and T1) and
      presence of the GSTP1 val allele (adjusted OR = 2.00, CI 1.14-3.52). Overall,
      there was no significant difference in frequency of p53 mutation among patients
      with different genotypes. Among patients with p53 mutation, transversions were
      significantly more frequent in GSTM1-negative as compared to GSTM1-positive
      individuals (OR = 5.18, CI 1.07-25.02, adjusted for age, sex and tumour stage).
      With one exception, all tumours with the most common type of transversion, G:C
      C:G, occurred in GSTM1-negative patients. Among smokers, all transversions (3 of
      3), but only 2 of 13 transitions, were found among carriers of the GSTP1 variant
      allele, and samples carrying at least 1 variant GSTP1 allele had more transitions
      at CpG sites than wild-type samples (adjusted OR = 4.61, CI 0.82-26.04). No
      significant associations were found for the NAT2 gene. Our results suggest that
      impaired glutathione conjugation may affect the mutation spectrum in critical
      target genes.

PMID- 15499623
TI  - L-carnitine inhibits hepatocarcinogenesis via protection of mitochondria.
AB  - Hepatocellular carcinoma is usually preceded by chronic inflammation. However,
      the molecular mechanism in hepatocarcinogenesis is not well known. Recently, we
      reported that mitochondrial dysfunction plays an important role in
      hepatocarcinogenesis via the production of free radicals. Furthermore, we proved
      that L-carnitine effectively protects mitochondrial function in vivo. Therefore,
      we investigated whether long-term administration of L-carnitine could prevent
      hepatitis and subsequent hepatocellular carcinoma in Long-Evans Cinnamon rats
      that are often analyzed as a model of hepatocarcinogenesis. The results indicated
      that oxidative stress elicited from abnormally accumulated copper increased the
      amount of free fatty acids, thereby inducing mitochondrial dysfunction, resulting
      in cell death and enhanced secondary generation of reactive oxygen species, which
      were significantly inhibited by carnitine treatment. Finally, the occurrence of
      placental glutathione S-transferase-positive foci as a marker for preneoplastic
      lesions and hepatocarcinogenesis were significantly inhibited by L-carnitine.
      These facts suggest that mitochondrial injury plays an essential role in the
      development of hepatocarcinogenesis and that the clinical use of carnitine has
      excellent therapeutic potential in individuals with chronic hepatitis.

PMID- 15499622
TI  - Dietary intervention in prostate cancer patients: PSA response in a randomized
      double-blind placebo-controlled study.
AB  - The objective of this study was to show or to exclude an effect of dietary
      supplement on rising prostate-specific antigen (PSA) levels. We have studied the
      effect of a dietary supplement (verum, administered for 6 weeks) containing plant
      estrogens, antioxidants, including carotenoids, selenium and other putative
      prostate cancer inhibiting substances in a randomized placebo-controlled double
      blind crossover study in 37 hormonally untreated men with prostate cancer and
      increasing PSA levels. Outcome measures were changes in the rates of change of
      serum concentrations of total and free PSA and changes in male sex hormone
      levels. Male sex hormone levels were significantly lower during the verum phase
      (DHT: -0.11 nmol/L, p = 0.005; testosterone: -1 nmol/L, p = 0.02). Total PSA
      doubling time was unaffected. Free PSA, which increased during the placebo phase
      (average doubling time of 68 weeks), decreased during the verum period (average
      half-life of 13 weeks; p = 0.02). In those men in whom the free androgen index
      decreased (21 out of 32), a significant decrease in the slopes of both total and
      free PSA was observed (p = 0.04). Overall total PSA doubling times did not
      increase significantly during verum. However, the study demonstrates that this
      dietary intervention reduces DHT and testosterone levels and increases free PSA
      doubling time (and total PSA doubling time in a relevant subgroup). If future
      studies confirm that these observations translate into a slowing of disease
      progression, a dietary intervention may become an attractive option for prostate
      cancer treatment and prevention.

PMID- 15499624
TI  - Invasiveness of breast cancer cells MDA-MB-231 through extracellular matrix is
      increased by the estradiol metabolite 4-hydroxyestradiol.
AB  - In malignant breast cancer, estrogen metabolism is altered, favoring the
      accumulation of hydroxyestradiols, which can generate free radicals. These
      reactive species can activate matrix metalloproteinases (MMPs), which in turn can
      hydrolyze the proteins of the extracellular matrix (ECM) that act as a barrier to
      tumor cell passage. The aim of this study was to determine whether reactive
      oxygen species generated by 4-hydroxyestradiol (4-OHE(2)) can activate MMP-2 and
      then enhance the invasiveness of breast cancer cells MDA-MB-231 in vitro.
      Enzymatic assay and gel zymography demonstrated that 4-OHE(2) at a concentration
      as low as 10(-8) M led to the conversion of proMMP-2 to active MMP-2. Activation
      of proMMP-2 by 4-OHE(2) was inhibited by the Cu,Zn-SOD supporting the involvement
      of the free radical superoxide anion (O(2)(*-)). Using invasion chambers coated
      with matrigel (artificial ECM), 4-OHE(2) (10(-8) M) enhanced the invasiveness of
      MDA-MB-231 breast cancer cells by 3-fold. The addition of Cu,Zn-SOD reduced the
      invasiveness of MDA-MB-231 cells by more than 2-fold, supporting the involvement
      of O(2)(*-) generated by 4-OHE(2). Addition of an MMP-2 inhibitor completely
      inhibited the enhancement of invasiveness induced by 4-OHE(2), which demonstrates
      the importance of activating MMP-2 by 4-OHE(2). On the other hand, estradiol,
      which does not have a catechol structure, did not generate free radicals, and it
      could not activate proMMP-2 or enhance the invasiveness of beast cancer cells.
      Although these data need to be confirmed in an animal model, this study suggests
      that the accumulation of 4-OHE(2) in breast tumors could enhance the invasiveness
      of breast cancer cells.

PMID- 15499625
TI  - Celecoxib derivatives induce apoptosis via the disruption of mitochondrial
      membrane potential and activation of caspase 9.
AB  - Celecoxib is a potent nonsteroid antiinflammatory drug (NSAID) that has shown
      great promise in cancer chemoprevention and treatment. The tumor suppression
      activity of celecoxib and other NSAIDs have been related to the induction of
      apoptosis in many cancer cell lines and animal models. While celecoxib is a
      specific inhibitor of cyclooxygenase (COX)-2, recent data indicate that its
      apoptotic properties may also be mediated through COX-independent pathways. In
      our study, we evaluated second generation celecoxib derivatives, lacking COX-2
      inhibitory activity, in a premalignant and malignant human oral cell culture
      model to determine their potential anticancer effect and mechanisms responsible
      for the COX-independent apoptotic activity. Celecoxib and its derivatives delayed
      the progression of cells through the G(2)/M phase and induced apoptosis. The
      derivatives with apolar substituents at the terminal phenyl moiety of celecoxib
      greatly enhanced apoptosis and cell cycle delay. Apoptosis and cell cycle arrest
      appeared to be independent of derivative induced inhibition of PDK1 and
      phosphorylation of Akt and Erk1/2. Derivatives induced apoptosis was mediated by
      the cleavage and activation of caspase-9 and caspase-3, but not caspase 8,
      implicating the mitochondrial pathway for apoptosis induction. Inhibitors of
      caspase-3 and caspase-9 and cyclosporin A, a mitochondrial membrane potential
      stabilizer, attenuated derivative induced apoptosis. Inhibition of caspase-3
      prevented the activation of caspase 8, while the inhibition of caspase-9
      inhibitor blocked activation of both caspase 3 and 8 by the derivatives.
      Apoptosis was independent of Bcl-2. These results indicate that the second
      generation celecoxib derivatives induce apoptosis in human oral cancer lines by
      the disruption of mitochondrial membrane potential activating caspase 9 and
      downstream caspase 3 and 8. This suggests that the modification of the celecoxib
      structure can lead to highly effective COX-independent growth inhibitory and
      apoptotic agents in chemoprevention and therapy.

PMID- 15499626
TI  - Impact of the coxsackie and adenovirus receptor (CAR) on glioma cell growth and
      invasion: requirement for the C-terminal domain.
AB  - Expression of the coxsackie and adenovirus receptor (CAR) is downregulated in
      malignant glioma cell lines and is barely detectable in high-grade primary
      astrocytoma (glioblastoma multiforme). We determined the effect of forced CAR
      expression on the invasion and growth of the human glioma cell line U87-MG, which
      does not express any CAR. Although retrovirally mediated expression of full
      length CAR in U87-MG cells did not affect monolayer growth in vitro, it did
      reduce glioma cell invasion in a 3-dimensional spheroid model. Furthermore, in
      xenograft experiments, intracerebral implantation of glioma cells expressing full
      length CAR resulted in tumors with a significantly reduced volume compared to
      tumors generated by control vector-transduced U87-MG cells. In contrast, U87-MG
      cells expressing transmembrane CAR with a deletion of the entire cytoplasmic
      domain (except for the first 2 intracellular juxtamembrane cysteine amino acids)
      had rates of invasion and tumor growth that were similar to those of the control
      cells. This difference in behavior between the 2 forms of CAR was not due to
      improper cell surface localization of the cytoplasmically deleted CAR as
      determined by comparable immunostaining of unpermeabilized cells, equivalent
      adenoviral transduction of the cells and similar extent of fractionation into
      lipid-rich domains. Taken together, these results suggest that the decrease or
      loss of CAR expression in malignant glioma may confer a selective advantage in
      growth and invasion to these tumors.

PMID- 15499627
TI  - Histone deacetylase inhibitors upregulate plakoglobin expression in bladder
      carcinoma cells and display antineoplastic activity in vitro and in vivo.
AB  - Histone deacetylase inhibitors (HDACis) are emerging as a promising new class of
      anticancer agents displaying growth-inhibitory activity and low toxicity in vivo.
      In this study, we examined the effect of sodium butyrate (NaB) and trichostatin A
      (TSA) on the growth of human bladder carcinoma cell lines in culture and TSA on
      the growth of EJ and UM-UC-3 human bladder xenografts in nude mice. NaB and TSA
      suppressed the growth of bladder cell lines at millimolar (1.5-4.3 mM) and
      micromolar (0.03-0.33 microM) concentrations, respectively, inducing
      concentration-dependent cell death. Bladder carcinoma cells within the
      experimental panel displayed the phenotype of late-stage bladder lesions
      expressing N-cadherin in the absence of E-cadherin accompanied by low levels of
      plakoglobin expression. Exposure of these cells to HDACis resulted in
      upregulation of plakoglobin with no change in E-cadherin expression. A 2-hr
      exposure to TSA was the minimal time required to upregulate plakoglobin in cells
      with downregulation to baseline levels occurring within 24 hr following drug
      removal. In mice bearing EJ and UM-UC-3 bladder xenografts, TSA (500
      microg/kg/day) caused suppression of tumor growth compared with mice receiving
      vehicle alone. A > 70% reduction in mean final tumor volume was recorded in both
      bladder xenograft models with no detectable toxicity. The results suggest that
      TSA inhibits bladder carcinoma cell growth and may be a useful, relatively
      nontoxic agent for consideration in the treatment of late-stage bladder tumors.

PMID- 15499629
TI  - Centrosome abnormalities in ovarian cancer.
AB  - Centrosome abnormalities have been found in various cancer types and are thought
      to be involved in early development of cancer and/or progression. The
      contribution of centrosome abnormalities to ovarian tumorigenesis has not been
      previously evaluated. We sought to determine whether centrosome dysfunction
      occurs in ovarian tumorigenesis, and whether it could be used as an indicator of
      early neoplastic changes in ovarian surface epithelium (OSE). Primary cultures of
      normal OSE and ovarian tumors, as well as paraffin-embedded normal ovaries and
      ovarian tumors of different stages, were used for immunostaining with a gamma
      tubulin antibody. Centrosomes were considered abnormal if there were more than 2
      per cell, if their sizes were greater than 2-fold of a normal centrosome, and/or
      if they were abnormal in shape. Centrosomes in normal tissue were uniform in
      size, whereas centrosomes in ovarian tumors tended to be abnormal in size, number
      and shape. On average, 4.7% of cells in 5 primary normal OSE cultures had more
      than 2 centrosomes, whereas 14.1% of primary cells from 5 ovarian tumors
      displayed centrosome abnormalities (p = 0.008). Centrosome abnormalities were
      present in 60.9% of stage I (n = 23), 83.3% of stage II (n = 30) and all stage
      III (n = 10) paraffin-embedded ovarian tumor samples examined, but not in normal
      tissues. In addition, centrosome abnormalities occurred more frequently in
      ovarian tumors with higher grade and aggressive serous subtype. This is the first
      demonstration that centrosome abnormalities occur in ovarian tumors. Centrosome
      dysfunction may be an early event in ovarian carcinogenesis and involved in
      ovarian tumor progression.

PMID- 15499628
TI  - Increased expression of prostate-specific G-protein-coupled receptor in human
      prostate intraepithelial neoplasia and prostate cancers.
AB  - The G-protein-coupled receptors and signal transduction pathways represent
      important specific targets for a variety of human diseases, ranging from the
      control of blood pressure, allergic response, hormonal disorders and neurologic
      diseases to tumorigenesis. Most recently, we and others have identified a novel
      human prostate-specific G-protein coupled receptor (PSGR). To investigate the
      potential roles of PSGR in human normal prostate and prostate cancers, we
      examined the expression level of PSGR in 146 human prostate samples with real
      time quantitative reverse transcription-PCR and in situ hybridization method. We
      significantly extended previous studies and demonstrated that PSGR is
      specifically expressed in human prostate tissues, not in any other normal and
      tumor samples tested. Compared to normal and benign prostatic hyperplasia
      tissues, the expression of PSGR increased significantly in human prostate
      intraepithelial neoplasia (PIN) and prostate tumors (approximately 10-fold),
      especially in early prostate tumors, suggesting PSGR may play an important role
      in early prostate cancer development and progression. The sensitivity and
      specificity estimates for PSGR expression were calculated as the area under the
      receiver-operating characteristics curve (0.902), indicating high-level
      sensitivity and specificity for discriminating benign prostate tissues from
      malignant prostate tissues. The association of PSGR expression with clinical
      parameters (clinical stages, Gleason scores, recurrent status and metastasis) was
      also investigated in this study. Our data suggest that overexpression of PSGR in
      human PIN and prostate cancers have the potential for early prostate cancer
      detection and diagnosis.

PMID- 15499630
TI  - High expression of bfl-1 contributes to the apoptosis resistant phenotype in B
      cell chronic lymphocytic leukemia.
AB  - In order to identify regulatory genes involved in the development of an apoptosis
      resistant phenotype in patients with chemotherapy refractory B-cell chronic
      lymphocytic leukemia (B-CLL) expression of apoptosis-regulating genes in B-CLL
      cells was quantified using cDNA arrays and RT-PCR. Data were obtained from and
      compared between 2 groups of B-CLL patients with either nonprogressive, indolent,
      previously untreated disease and with leukemic cells sensitive to in vitro
      fludarabine-induced apoptosis, referred to as sensitive B-CLL (sB-CLL) or with
      progressive, chemotherapy refractory disease and with leukemic cells resistant to
      in vitro fludarabine-induced apoptosis, referred to as resistant B-CLL (rB-CLL).
      By performing a supervised clustering of genes that most strongly discriminated
      between rB-CLL vs. sB-CLL a small group of genes was identified, where bfl-1 was
      the strongest discriminating gene (p < 0.05), with higher expression in rB-CLL. A
      group of apoptosis-regulating genes were modulated during induction of apoptosis
      by serum deprivation in vitro in a similar manner in all cases studied. However,
      bfl-1 was preferentially downregulated in sB-CLL as compared to rB-CLL (p <
      0.05). We conclude that bfl-1 may be an important regulator of B-CLL apoptosis,
      which could contribute to disease progression and resistance to chemotherapy, and
      as such represent a future potential therapeutic target.

PMID- 15499632
TI  - Treatment of multiple sclerosis with an anti-interleukin-2 receptor monoclonal
      antibody.
AB  - We examined whether treatment with daclizumab, a humanized monoclonal antibody
      specific for the interleukin-2 receptor alpha chain, was safe and efficacious in
      relapsing-remitting and secondary progressive multiple sclerosis patients.
      Nineteen ambulatory patients with clinically active disease were treated for 5 to
      25 months. Seventeen patients were not responding to other immunotherapies.
      Daclizumab was generally well tolerated. Sustained clinical improvement (10
      patients) or stabilization (9 patients) was observed. Daclizumab treatment
      produced significant reduction in magnetic resonance imaging activity.

PMID- 15499631
TI  - Genetic polymorphism of the interferon-gamma gene in cervical carcinogenesis.
AB  - Beyond human papillomavirus (HPV) infection, host genetic factors may contribute
      to cervical carcinogenesis. This study aims to test the hypothesis that CA
      dinucleotide repeat polymorphism in the first intron of the interferon-gamma (IFN
      gamma) gene is associated with HPV-initiated cervical carcinogenesis. A hospital
      based case-control study including patients with low-grade squamous
      intraepithelial lesions (LSILs; n = 93), high-grade squamous intraepithelial
      lesions (HSILs; n = 123) and invasive carcinomas (n = 153) of the uterine cervix,
      as well as 1:1 age-matched controls, was conducted. The IFN-gamma genotype was
      determined by PCR and capillary electrophoresis with internal standards. HPV
      genotype was determined by consensus PCR and reverse line blot hybridization.
      Genotypes containing the 12 or 14 allele (12 or 14 CA repeats) were significantly
      more common in patients with HSILs than in controls (46% vs. 22%; OR = 3.0; 95%
      CI = 1.7-5.2; p < 0.0001). In contrast, genotypes containing 13 and 18 were
      significantly more common in controls than in patients with HSILs (76% vs. 53%;
      OR = 0.3; 95% CI = 0.2-0.6; p = 0.0001) or squamous cell carcinomas (74% vs. 63%;
      OR = 0.6; 95% CI = 0.4-1.0; p = 0.037). The frequency of the 12 and 14 genotypes
      increased significantly in accordance with the severity of cervical
      carcinogenesis (p(test for trend) = 0.0002), whereas the 13 and 18 genotypes
      showed the opposite trend (p(test for trend) = 0.007). Comparing IFN-gamma
      genotype and HPV status, 18-containing genotypes were more frequently found in
      HPV(+) LSILs, and 12-containing genotypes were less frequently found in HPV(+)
      HSILs. Compared with non-13 genotypes, 13 genotype HSILs were more frequently
      infected with HPV58 (70% vs. 45%) and less frequently infected with HPV18 (0% vs.
      16%; p= 0.007). Genetic polymorphism of the IFN-gamma gene is associated with
      individual susceptibility to cervical carcinogenesis. This polymorphism
      correlates with HPV infection in a disease- and type-specific manner.

PMID- 15499633
TI  - Detection of epithelial ovarian cancer using 1H-NMR-based metabonomics.
AB  - Currently available serum biomarkers are insufficiently reliable to distinguish
      patients with epithelial ovarian cancer (EOC) from healthy individuals.
      Metabonomics, the study of metabolic processes in biologic systems, is based on
      the use of (1)H-NMR spectroscopy and multivariate statistics for biochemical data
      generation and interpretation and may provide a characteristic fingerprint in
      disease. In an effort to examine the utility of the metabonomic approach for
      discriminating sera from women with EOC from healthy controls, we performed (1)H
      NMR spectroscopic analysis on preoperative serum specimens obtained from 38
      patients with EOC, 12 patients with benign ovarian cysts and 53 healthy women.
      After data reduction, we applied both unsupervised Principal Component Analysis
      (PCA) and supervised Soft Independent Modeling of Class Analogy (SIMCA) for
      pattern recognition. The sensitivity and specificity tradeoffs were summarized
      for each variable using the area under the receiver-operating characteristic
      (ROC) curve. In addition, we analyzed the regions of NMR spectra that most
      strongly influence separation of sera of EOC patients from healthy controls. PCA
      analysis allowed correct separation of all serum specimens from 38 patients with
      EOC (100%) from all of the 21 premenopausal normal samples (100%) and from all
      the sera from patients with benign ovarian disease (100%). In addition, it was
      possible to correctly separate 37 of 38 (97.4%) cancer specimens from 31 of 32
      (97%) postmenopausal control sera. SIMCA analysis using the Cooman's plot
      demonstrated that sera classes from patients with EOC, benign ovarian cysts and
      the postmenopausal healthy controls did not share multivariate space, providing
      validation for the class separation. ROC analysis indicated that the sera from
      patients with and without disease could be identified with 100% sensitivity and
      specificity at the (1)H-NMR regions 2.77 parts per million (ppm) and 2.04 ppm
      from the origin (AUC of ROC curve = 1.0). In addition, the regression
      coefficients most influential for the EOC samples compared to postmenopausal
      controls lie around delta3.7 ppm (due mainly to sugar hydrogens). Other loadings
      most influential for the EOC samples lie around delta2.25 ppm and delta1.18 ppm.
      These findings indicate that (1)H-NMR metabonomic analysis of serum achieves
      complete separation of EOC patients from healthy controls. The metabonomic
      approach deserves further evaluation as a potential novel strategy for the early
      detection of epithelial ovarian cancer.

PMID- 15499634
TI  - Plasma folate, vitamin B12, and homocysteine and prostate cancer risk: a
      prospective study.
AB  - The role of folate metabolism in cancer development is a topic of much current
      interest, with maintenance of adequate folate status tending to show a protective
      effect. Aberrant methylation, primarily hypermethylation of certain genes
      including tumor suppressors, has been implicated in prostate cancer development.
      Folate, vitamin B12 and homocysteine are essential for methyl group metabolism
      and thus also for DNA methylation. We related plasma levels of these factors to
      prostate cancer risk in a prospective study of 254 case subjects and 514 matched
      control subjects. Increasing plasma levels of folate and vitamin B12 were
      statistically significantly associated with increased prostate cancer risk, with
      an odds ratio of 1.60 (95% CI = 1.03-2.49; p(trend) = 0.02) for folate and 2.63
      (95% CI = 1.61-4.29; p(trend) < 0.001) for vitamin B12 for highest vs. lowest
      quartile. Increasing plasma homocysteine levels were associated with a reduced
      risk of borderline significance (OR = 0.67; 95% CI = 0.43-1.04; p(trend) = 0.08).
      After adjustment for the other 2 plasma variables, body mass index and smoking, a
      statistically significant increased risk remained only for vitamin B12 (OR =
      2.96; 95% CI = 1.58-5.55; p(trend) = 0.001). Adjusted OR for folate and
      homocysteine were 1.30 (95% CI = 0.74-2.24; p(trend) = 0.17) and 0.91 (95% CI =
      0.51-1.58; p(trend) = 0.60), respectively. Our results suggest that factors
      contributing to folate status are not protective against prostate cancer. On the
      contrary, vitamin B12, associated with an up to 3-fold increase in risk, and
      possibly also folate, may even stimulate prostate cancer development. These
      findings are novel and should be explored further in future studies.

PMID- 15499635
TI  - Genes upregulated in a metastasizing human colon carcinoma cell line.
AB  - Differential gene expression between the metastatic human colon cancer cell line
      HT29p and its nonmetastatic counterpart HT29-MTX was revealed by suppression
      subtractive hybridization. Fifty-eight individual genes showed increased mRNA
      levels in HT29p cells. Only 15 of these genes had been related to transformation
      in previous studies; the majority of genes are new candidates encoding proteins
      relevant for the metastatic process. Cancer profiling arrays as well as in situ
      hybridization study revealed that at least some of the genes obtained in the SSH
      screen are also differentially expressed in human tumors.

PMID- 15499636
TI  - Bone marrow genesis after subcutaneous delivery of rat osteogenic cell-seeded
      biodegradable scaffolds into nude mice.
AB  - This study describes the generation of an active hematopoietic marrow within the
      confines of a biodegradable, macroporous polyester scaffold, seeded with rat
      osteogenic cells, after subcutaneous implantation in nude mice. A macroporous,
      poly(DL-lactide-co-glycolide) polymer scaffold, into which resorbable calcium
      phosphate particles were incorporated, was seeded with rat bone marrow-derived
      cells. Scanning electron microscopy of the cell-seeded scaffold demonstrated
      confluent cell colonization. Scaffolds seeded with cells were implanted under the
      dorsum of immunocompromised mice for 5 weeks. Histological analysis revealed bone
      formation along the scaffold pores creating bony cavities within which a host
      derived, hematopoietic marrow was observed which included hematopoietic
      precursors, megakaryocytes, fat cells, and numerous marrow sinusoids. In those
      areas where bone was not elaborated on the scaffold surface, no marrow genesis
      was observed and the scaffold interstices were filled with fibrous tissue. These
      results demonstrate the utility of this biodegradable scaffold in delivery of a
      phenotypically functional cell population for bone tissue and bone marrow
      engineering applications. Moreover, the recapitulation of hematopoietic marrow
      tissue within the engineered bony cavities also provides a new experimental
      environment with which to further investigate the interactions of hematopoietic
      and nonhematopoietic compartments of the marrow microenvironment.

PMID- 15499637
TI  - Molecular characterization of an improved vector for evaluation of the tumor
      suppressor versus oncogene abilities of the androgen receptor.
AB  - BACKGROUND: There is a growing body of evidence demonstrating that the function
      of the ligand-occupied androgen receptor (AR) within the nuclei of normal
      prostatic epithelial cells acts as a tumor suppressor gene. This is in contrast
      to the well-documented ability of the AR within prostate cancer cells to function
      as an oncogene. Thus, many groups are attempting to understand the biochemistry
      and signaling cascade differences involved in the switching of AR from a tumor
      suppressor to an oncogene. METHODS: To do this, of plasmid vectors for transgenic
      expression of AR are very useful. AR negative PC-3 human prostate cancer cells
      were transfected with a plasmid containing the full length coding sequence of AR
      without its 5'- or 3'-untranslated regions (UTRs) (i.e., pSG5-AR). RESULTS:
      Transgenic expression of the AR protein results in profound growth inhibition
      which is not relieved by the addition of ligand. A new expression vector for the
      AR, pAR-IRES-EGFP, has been constructed that contains full-length 5'-UTR which
      includes the identified translation regulatory regions, the full length coding
      sequence and the partial 3'-UTR, which includes the identified post
      transcriptional regulatory regions. When PC-3 cells were transfected with the pAR
      IRES-EGFP vector, it was found that transgenic AR protein expression was not
      growth inhibitory until ligand was added. CONCLUSIONS: These pSG5-AR versus pSAR
      IRES-EGFP clones are being studied to determine the molecular pathways explaining
      their different response to AR and ligand.

PMID- 15499638
TI  - Photoexcited formation of bone apatite-like coatings on micro-arc oxidized
      titanium.
AB  - A novel method to rapidly deposit bone apatite-like coatings on titanium implants
      in simulated body fluid (SBF) is proposed in this article. The processing was
      composed of two steps; for example, micro-arc oxidation (MAO) of titanium to form
      titania films, and UV-light illumination of the titania-coated titanium in SBF.
      The morphology, crystalline structure, and bond strength of the MAO films were
      investigated as a function of the applied voltage (in the range of 250-400 V) by
      using scanning electron microscopy, transmission electron microscopy, energy
      dispersive X-ray spectrometry, Fourier transform infrared spectroscopy, adhesion
      tensile test, and scratch test. Results showed that the MAO films were porous and
      nanocrystalline with pore sizes varying from 1 to 3 microm and grain sizes
      varying from 10-20 to 70-80 nm; the predominant phase in titania films changed
      from anatase to rutile, and the bond strength of the films decreased from 43.4 to
      32.9 MPa as the applied voltage increased from 250 to 400 V. After UV-light
      illumination of the films in SBF for 2 h, bone apatite-like coating was deposited
      on the MAO film formed at 250 V. The bond strength of the apatite/titania bilayer
      was about 44.2 MPa. However, no apatite was observed on the MAO film formed at
      400 V after UV-light illumination.

PMID- 15499640
TI  - Randomized clinical trial of the effects of preoperative and postoperative oral
      nutritional supplements on clinical course and cost of care (Br J Surg 2004; 91:
      983-990).

PMID- 15499641
TI  - Meta-analysis of randomized clinical trials of colorectal surgery with or without
      mechanical bowel preparation (Br J Surg 2004; 91: 1125-1130).

PMID- 15499642
TI  - Randomized clinical trial of the effect of pneumoperitoneum on cardiac function
      and haemodynamics during laparoscopic cholecystectomy (Br J Surg 2004; 91: 848
      854).

PMID- 15499643
TI  - Contrast-enhanced ultrasonography during liver surgery (Br J Surg 2004; 91: 1165
      1167).

PMID- 15499644
TI  - Long-term outcome of laparoscopic ventral rectopexy for total rectal prolapse.
AB  - BACKGROUND: Postoperative constipation is a common problem with most mesh
      suspension techniques used to correct rectal prolapse. Autonomic denervation of
      the rectum subsequent to its complete mobilization has been suggested as a
      contributory factor. The aim of this study was to assess the long-term outcome of
      patients who underwent a novel, autonomic nerve-sparing, laparoscopic technique
      for rectal prolapse. METHODS: Between 1995 and 1999, 42 patients had laparoscopic
      ventral rectopexy for total rectal prolapse. The long-term results after a median
      follow-up of 61 (range 29-98) months were analysed. RESULTS: There were no major
      postoperative complications. Late recurrence occurred in two patients. In 28 of
      31 patients with incontinence there was a significant improvement in continence.
      Symptoms of obstructed defaecation resolved in 16 of 19 patients. During follow
      up, new onset of mild obstructed defaecation was noted in only two patients.
      Symptoms suggestive of slow-transit colonic obstipation were not induced.
      CONCLUSION: Laparoscopic ventral rectopexy is an effective technique for the
      correction of rectal prolapse and appears to avoid severe postoperative
      constipation. The ventral position of the prosthesis may explain the beneficial
      effect on symptoms of obstructed defaecation.

PMID- 15499645
TI  - Intra-abdominal hypertension and the abdominal compartment syndrome (Br J Surg
      2004; 91: 1102-1110).

PMID- 15499646
TI  - Surgical treatment of rectal prolapse.

PMID- 15499647
TI  - Evidence-based practice requires evidence.

PMID- 15499648
TI  - Current standards of surgery for pancreatic cancer.
AB  - BACKGROUND: Pancreatic cancer carries a dismal prognosis but there has been a
      vast increase in evidence on its management in the past decade. METHODS: An
      electronic and manual search was performed for articles on the surgical treatment
      of pancreatic cancer published in the past 10 years. RESULTS: Six major areas of
      advancement were identified. Groups at high risk of developing pancreatic cancer,
      notably those with chronic pancreatitis and hereditary pancreatitis, have been
      defined, raising the need for secondary screening. Methods of staging pancreatic
      cancer for resection have greatly improved but accuracy is still only 85-90 per
      cent. Pylorus-preserving partial pancreatoduodenectomy without extended
      lymphadenectomy is the simplest procedure; it does not compromise long-term
      survival. Adjuvant chemotherapy significantly improves long-term survival.
      Patients who are free from major co-morbidity have better palliation by surgery
      (with a double bypass) than by endoscopy. High-volume centres improve the results
      of surgery for all outcome measures including long-term survival. CONCLUSION: The
      surgical management of pancreatic cancer has undergone a significant change in
      the past decade. It has moved away from no active treatment. The standard of care
      can now be defined as potentially curative resection in a specialist centre
      followed by adjuvant systemic chemotherapy.

PMID- 15499649
TI  - Strictureplasty.
AB  - BACKGROUND: Advances in the use of bowel-sparing surgery for Crohn's disease have
      led to the development of strictureplasty as an important technique to conserve
      small bowel length and reduce morbidity associated with malabsorption. METHODS: A
      literature review of long-term studies on strictureplasty was undertaken, and
      evidence of its safety and efficacy was evaluated. RESULTS: The safety and
      efficacy of strictureplasty is confirmed in retrospective studies carried out
      over a period of 5-10 years, particularly when employed in patients at risk of
      short bowel syndrome, but certain questions regarding bowel function and disease
      activity after surgery remain unanswered. There is also concern that diseased
      tissue is left in situ after strictureplasty; this tissue has the potential for
      malignant transformation in the long term. CONCLUSION: Strictureplasty has been
      used in surgery for Crohn's disease for the past 25 years. Studies have proven
      its efficacy in the treatment of carefully selected patients at risk of
      malabsorption owing to short bowel syndrome.

PMID- 15499650
TI  - Positron emission tomography in the staging and management of breast cancer.
AB  - BACKGROUND: Breast cancer is the commonest cause of cancer death in women in the
      Western world, and imaging is essential in its diagnosis and staging. Metabolic
      imaging is a novel approach to improving the detection of cancers, as malignant
      transformation of cells is often associated with increased metabolic activity.
      This review assesses the possible role of positron emission tomography (PET) as a
      single non-invasive imaging modality to replace or complement current imaging and
      surgical practices in the diagnosis and staging of breast cancer. METHODS AND
      RESULTS: A Medline search was performed and articles were cross-referenced with
      other relevant material. Evaluation of primary breast cancer with PET has shown a
      sensitivity of between 64 and 100 per cent and a specificity of 33-100 per cent;
      diagnostic accuracy appears to be related to tumour size. Difficulties arise in
      altered fluorodeoxyglucose uptake in lobular carcinoma, carcinoma in situ and
      benign inflammatory breast disease. In axillary staging, sensitivities of between
      25 and 100 per cent have been reported, but with a false-negative of up to 20 per
      cent. In the assessment of distant metastasis and asymptomatic patients with
      raised levels of tumour markers, PET was superior to conventional imaging
      modalities. CONCLUSION: PET is not a single diagnostic and staging tool that can
      replace current surgical, histological and radiological staging. Its main role in
      breast cancer lies in the investigation of metastatic disease and the evaluation
      of pathological response to various chemotherapeutic regimens.

PMID- 15499651
TI  - Randomized clinical trial of intraoperative autotransfusion in surgery for
      abdominal aortic aneurysm.
AB  - BACKGROUND: Perioperative homologous blood transfusion (HBT) is associated with
      adverse reactions and risks transmission of infection. It has also been
      implicated as an immunosuppressive agent. Intraoperative autotransfusion (IAT) is
      a potential method of autologous transfusion. METHODS: This was a single-centre
      randomized clinical trial of IAT in surgery for abdominal aortic aneurysm. Forty
      patients were randomized to IAT and 41 underwent surgery with HBT only. Patients
      in both groups received HBT to maintain haemoglobin levels above 8 g/dl.
      Transfusion requirements, and incidence of systemic inflammatory response
      syndrome (SIRS) and infection, were compared. RESULTS: Significantly fewer
      patients in the IAT group required HBT (21 versus 31; P = 0.038) and the median
      blood requirement per patient was 2 units lower (P = 0.012). There was a higher
      incidence of chest infection (12 versus four patients; P = 0.049) and SIRS (20
      versus nine patients; P = 0.020) in the HBT group. Risk of SIRS was related to
      aortic cross-clamp time in the IAT group only. CONCLUSION: Use of autotransfusion
      effectively reduced the need for HBT and was associated with a reduced incidence
      of postoperative SIRS and infective complications.

PMID- 15499652
TI  - Reversal of the silencing of tetracycline-controlled genes requires the
      coordinate action of distinctly acting transcription factors.
AB  - BACKGROUND: Regulation of genes transferred to eukaryotic organisms is often
      limited by the lack of consistent expression levels in all transduced cells,
      which may result in part from epigenetic gene silencing effects. This reduces the
      efficacy of ligand-controlled gene switches designed for somatic gene transfers
      such as gene therapy. METHODS: A doxycycline-controlled transgene was stably
      introduced in human cells, and clones were screened for epigenetic silencing of
      the transgene. Various regulatory proteins were targeted to the silent transgene,
      to identify those that would mediate regulation by doxycycline. RESULTS: A
      doxycycline-controlled minimal promoter was found to be prone to gene silencing,
      which prevents activation by a fusion of the bacterial TetR DNA-binding domain
      with the VP16 activator. DNA modification studies indicated that the silenced
      transgene adopts a poorly accessible chromatin structure. Several cellular
      transcriptional activators were found to restore an accessible DNA structure when
      targeted to the silent transgene, and they cooperated with Tet-VP16 to mediate
      regulation by doxycycline. CONCLUSIONS: Reversal of the silencing of a
      tetracycline-regulated minimal promoter requires a chromatin-remodeling activity
      for subsequent promoter activation by the Tet-VP16 fusion protein. Thus, distinct
      regulatory elements may be combined to obtain long-term regulation and persistent
      expression of exogenous genes in eukaryotic cells.

PMID- 15499653
TI  - Glasgow Aneurysm Score as a predictor of immediate outcome after surgery for
      ruptured abdominal aortic aneurysm.
AB  - BACKGROUND: The aim of the study was to assess the value of the Glasgow Aneurysm
      Score in predicting postoperative death after repair of a ruptured abdominal
      aortic aneurysm (AAA). METHODS: Between 1991 and 1999, 836 patients underwent
      surgery for ruptured AAA. Their operative risk at presentation was evaluated
      retrospectively using the Glasgow Aneurysm Score, based on data from the
      nationwide Finnvasc registry. RESULTS: The operative mortality rate was 47.2 per
      cent (395 of 836); 164 patients (19.6 per cent) had cardiac complications and 164
      (19.6 per cent) required intensive care treatment for more than 5 days.
      Predictors of postoperative death in univariate analysis were: coronary artery
      disease (P = 0.005), preoperative shock (P < 0.001), age (P < 0.001), and the
      Glasgow Aneurysm Score (P < 0.001). In multivariate analysis the predictors were:
      preoperative shock (odds ratio (OR) 2.13 (95 per cent confidence interval (c.i.)
      1.45 to 3.11); P < 0.001) and the Glasgow Aneurysm Score (for an increase of ten
      units: OR 1.81 (95 per cent c.i. 1.54 to 2.12); P < 0.001). Receiver-operator
      characteristic (ROC) curves showed that the best cut-off value of the Glasgow
      Aneurysm Score in predicting postoperative death was 84 (area under the curve
      0.75 (95 per cent c.i. 0.72 to 0.78), standard error 0.17; P < 0.001). The
      operative mortality rate was 28.2 per cent (114 of 404) in patients with a
      Glasgow Aneurysm Score of 84 or less, compared with 65.0 per cent (281 of 432) in
      those with a score greater than 84 (P < 0.001). CONCLUSION: The Glasgow Aneurysm
      Score predicted postoperative death after repair of ruptured AAA in this series.

PMID- 15499654
TI  - Aurora-C kinase is a novel chromosomal passenger protein that can complement
      Aurora-B kinase function in mitotic cells.
AB  - The function of Aurora-C kinase, a member of the Aurora kinase family identified
      in mammals, is currently unknown. We present evidence that Aurora-C, like Aurora
      B kinase, is a chromosomal passenger protein localizing first to centromeres and
      then to the midzone of mitotic cells. Aurora-C transcript is expressed at a
      moderate level albeit about an order of magnitude lower than Aurora-B transcript
      in diploid human fibroblasts. The level of Aurora-C transcript is elevated in
      several human cancer cell types. Aurora-C and Aurora-B mRNA and protein
      expressions are maximally elevated during the G2/M phase but their expression
      profiles in synchronized cells reveal differential temporal regulation through
      the cell cycle with Aurora-C level peaking after that of Aurora-B during the
      later part of the M phase. Aurora-C, like Aurora-B, interacts with the inner
      centromere protein (INCENP) at the carboxyl terminal end spanning the conserved
      IN box domain. Competition binding assays and transfection experiments revealed
      that, compared with Aurora-C, Aurora-B has preferential binding affinity to
      INCENP and co-expression of the two in vivo interferes with INCENP binding,
      localization, and stability of these proteins. A kinase-dead mutant of Aurora-C
      had a dominant negative effect inducing multinucleation in a dose-dependent
      manner. siRNA mediated silencing of Aurora-C and Aurora-B also gave rise to
      multinucleated cells with the two kinases silenced at the same time displaying an
      additive effect. Finally, Aurora-C could rescue the Aurora-B silenced
      multinucleation phenotype, demonstrating that Aurora-C kinase function overlaps
      with and complements Aurora-B kinase function in mitosis.

PMID- 15499657
TI  - Electrospray ionization mass spectral characteristics and fragmentation
      mechanisms of novel photoinduced DNA-cleaving agents formed as conjugates of
      haloarenes and polyamides containing N-methylimidazole.

PMID- 15499658
TI  - Analysis of DNA methylation by tandem ion-pair reversed-phase high-performance
      liquid chromatography/electrospray ionization mass spectrometry.

PMID- 15499659
TI  - Minimization of carbon addition during derivatization of monosaccharides for
      compound-specific delta13C analysis in environmental research.
AB  - Little is known about the delta13C composition of monosaccharides representing
      the largest carbon reservoir in the biosphere. The main reason for this might be
      that monosaccharides have to be derivatized prior to gas
      chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) analyses
      and that a large isotopic correction is necessary for the carbon that has to be
      added to the original molecule during derivatization, resulting in large
      uncertainty of the calculated delta13C values of individual monosaccharides. The
      amount of added derivatization carbon is twice (alditol acetates) or even three
      times (trimethylsilyl (TMS) derivatives) as high as the amount of the original
      monosaccharide carbon. In addition, isotope fractionation occurs during
      acetylation. Therefore, the objectives of this study were (i) to minimize carbon
      addition during derivatization for GC/C/IRMS measurements of monosaccharides in
      soil and sediment samples and (ii) to quantify improvements in accuracy and
      precision of the final results. Minimization of carbon addition was accomplished
      by derivatization with methylboronic acid (MBA) and TMS thereafter (MBA method).
      Monosaccharides derivatized with the MBA method instead of TMS reduced the number
      of added carbon atoms from 2.2-2.7 to 0.3-0.8 per sugar carbon atom. Although the
      precision of GC/C/IRMS measurements with both methods is comparable (about 0.3
      per thousand), delta13C values of an internal standard indicated that the newly
      developed MBA method is about 2 per thousand more accurate than the TMS method.
      delta13C comparison between soil samples that differed only slightly in their
      bulk carbon isotope signature showed that the MBA method is better in proving
      these small differences on a significant level. Total precision of the whole MBA
      method including all analytical and calculation steps is better by a factor of
      almost three than the TMS method.

PMID- 15499660
TI  - Simultaneous determination of delta33S(V-CDT) and delta34S(V-CDT) using masses
      48, 49 and 50 on a continuous flow isotope ratio mass spectrometer.
AB  - A new, fast, continuous flow technique is described for the simultaneous
      determination of delta33S and delta34S using SO masses 48, 49 and 50. Analysis
      time is approximately 5 min/sample with measurement precision and accuracy better
      than +/-0.3 per thousand. This technique, which has been set up using IAEA Ag2S
      standards S-1, S-2 and S-3, allows for the fast determination of mass-dependent
      or mass-independent fractionation (MIF) effects in sulfide, organic sulfur
      samples and possibly sulfate. Small sample sizes can be analysed directly,
      without chemical pre-treatment. Robustness of the technique for natural versus
      artificial standards was demonstrated by analysis of a Canon Diablo troilite,
      which gave a delta33S of 0.04 per thousand and a delta34S of -0.06 per thousand
      compared to the values obtained for S-1 of 0.07 per thousand and -0.20 per
      thousand, respectively. Two pyrite samples from a banded-iron formation from the
      3710 Ma Isua Greenstone Belt were analysed using this technique and yielded MIF
      (Delta33S of 2.45 and 3.31 per thousand) comparable to pyrite previously analysed
      by secondary ion probe.

PMID- 15499661
TI  - Quantitation of 17alpha-ethinylestradiol in aquatic samples using liquid-liquid
      phase extraction, dansyl derivatization, and liquid chromatography/positive
      electrospray tandem mass spectrometry.
AB  - A rapid and sensitive method for the analysis of 17alpha-ethinylestradiol (EE2)
      in environmental aqueous samples has been developed. Aquatic samples were
      extracted using liquid-liquid extraction, and organic phase extracts were
      concentrated and derivatized with dansyl chloride. Analysis was performed using
      high-performance liquid chromatography with positive electrospray ionization and
      tandem mass spectrometry (HPLC/ESI-MS/MS). Deuterated 17alpha-ethinylestradiol
      was used as internal standard and was added to samples before extraction. A limit
      of quantitation of 1 ng/L was obtained using a 25 mL aqueous sample. The average
      recovery of EE2 spiked into a 25 mL tapwater sample was 100%. This highly
      sensitive quantitation method is useful for measuring low levels of EE2 in
      aqueous environmental samples.

PMID- 15499662
TI  - An electrospray ionization tandem mass spectrometry based system with an online
      dual-loop cleanup device for simultaneous quantitation of urinary benzene
      exposure biomarkers trans,trans-muconic acid and S-phenylmercapturic acid.
AB  - An electrospray ionization tandem mass spectrometry (ESI-MS/MS) system with an
      online dual-loop cleanup device was developed for simultaneous quantitation of
      the urinary benzene exposure biomarkers trans,trans-muconic acid (ttMA) and S
      phenylmercapturic acid (SPMA). The cleanup device was constructed from an
      autosampler, two electrically operated two-position switching valves, a reversed
      phase C18 trap cartridge, a 200-microL loop, and two solvent-delivery pumps. The
      device was interfaced directly with a triple-quadrupole mass spectrometer and
      fully controlled by computer software and hardware. Because isotope dilution by
      introducing 13C-labeled ttMA and SPMA as internal standards was employed, the
      precision of the analytical system was high (for ttMA, intra- and inter-day CV
      values ranged from 3.82-4.53%; for SPMA, 2.13-7.06%). The calibration curves
      obtained using human urine spiked with ttMA were linear from 15.6-4000 microg/L
      (R = 0.9998) and SPMA at concentrations from 0.78-200 microg/L (R = 0.9993). The
      method detection limit (MDL) for SPMA was 0.23 microg/L. The MDL of ttMA could
      not be determined accurately because of unavailability of an appropriate blank
      urine matrix, but was estimated to be lower than 7.43 microg/L. Without tedious
      manual sample cleanup procedures the analytical system is fully automated and is
      therefore useful for high-throughput simultaneous determination of urinary ttMA
      and SPMA. The sample throughput is roughly 100 samples per day. With the
      selectivity and the sensitivity provided by MS/MS detection, the analytical
      system can be used for large-scale monitoring of environmental or occupational
      exposure of humans to benzene.

PMID- 15499663
TI  - Ion trap liquid chromatography/tandem mass spectrometry analysis of leukotriene
      B4 in exhaled breath condensate.
AB  - The objective of this study is the measurement of leukotriene B7 (LTB4), a potent
      inflammatory mediator, in exhaled breath condensate by using liquid
      chromatography/mass spectrometry (LC/MS and LC/MS/MS). Condensation of exhaled
      breath is a non-invasive method to collect airway secretions. Deuterated (d4)
      LTB4 was used as internal standard. The MS and MS/MS behavior of LTB4 and LTB4-d4
      was studied by electrospray ionization (ESI) and atmospheric pressure chemical
      ionization (APCI) in both positive and negative ion polarity mode. Preliminary
      results show that monitoring negative ions in ESI mode has the best sensitivity
      for both LTB4 and LTB4-d4. Therefore, negative ESI was chosen, and the [M-H]-
      ions at m/z 335 and 339 were selected for quantification. The lower limit of
      quantification for LTB4, expressed as the lowest point of the calibration curve,
      was 100 pg/mL. Using this technique, we measured LTB4 in exhaled breath
      condensate in two healthy subjects, four asthmatic patients on anti-inflammatory
      treatment, and four asthmatic patients who were not on anti-inflammatory drugs.
      Exhaled LTB4 concentrations were detected only in asthmatic patients who were not
      on anti-inflammatory therapy. This method is potentially useful for non-invasive
      assessment of airway inflammation, but the sensitivity of the technique needs to
      be improved.

PMID- 15499664
TI  - Analysis of urinary nucleosides. IV. Identification of urinary purine nucleosides
      by liquid chromatography/electrospray mass spectrometry.
AB  - Modified urinary nucleosides are potentially invaluable in cancer diagnosis. High
      performance liquid chromatography (HPLC) was combined with full scan mass
      spectrometry (MS), tandem mass spectrometry and MSn analysis in order to identify
      purine nucleosides purified from urine. UV peaks evident in the chromatogram were
      examined by the various mass spectrometric techniques and adenosine, 1
      methyladenosine, xanthosine, N1-methylguanosine, N2-methylguanosine, N2,N2
      dimethylguanosine, N2,N2,N7-trimethylguanosine, inosine, and 1-methylinosine were
      each identified in the urine samples from cancer patients. The benefits of the
      use of LC/MS compared with HPLC alone are discussed.

PMID- 15499665
TI  - Proceedings of the European Workshop on Gadovist: Insights in MR imaging. Malaga,
      Spain, October 2003.

PMID- 15499666
TI  - Embryonic stem-cell research.

PMID- 15499667
TI  - Embryonic stem-cell research.

PMID- 15499668
TI  - Combat duty in Iraq and Afghanistan and mental health problems.

PMID- 15499669
TI  - PSA velocity and prostate cancer.

PMID- 15499670
TI  - Prostate cancer with low PSA levels.

PMID- 15499671
TI  - Prostate cancer with low PSA levels.

PMID- 15499672
TI  - Prostate cancer with low PSA levels.

PMID- 15499673
TI  - Medicines for vegetarians.

PMID- 15499674
TI  - [Microsurgical approaches to the treatment of obstructive azoospermia].
AB  - In the past 5 to 10 years, very few fields in modern medicine have changed so
      dramatically as reproductive medicine, especially for the treatment of male
      infertility. Advances have been made in intracytoplasmic sperm injection (ICSI),
      refined microsurgical reconstructive techniques (vasovasostomy and
      vasoepididymostomy), and microsurgical techniques of surgical sperm retrieval
      from the epididymis and testis. All men with epididymal obstruction (obstructive
      azoospermia) now have the opportunity to father their own biological children. In
      this article, the authors reviewed the most updated microsurgical vasovasostomy,
      vasoepididymostomy techniques and surgical indications as well as the key factors
      for successful microsurgical treatment. They also predicted the future directions
      and discussed the advantages of microsurgical techniques, emphasized the
      significant roles of microsurgical training for urological doctors to treat male
      infertility.

PMID- 15499675
TI  - Analysis and occurrence of estrogen in wastewater in Japan.
AB  - This paper describes an analytical procedure for free estrogens and their
      conjugates in domestic wastewater. The procedure demonstrated in this study is
      innovative in terms of levels of detection and quantification of the following
      substances: estrone (E1); 17beta-estradiol (E2); 17alpha-ethynylestradiol (EE2);
      estriol (E3); estrone-3-sulfate (E1-S); beta-estradiol 3-sulfate (E2-S); estriol
      3-sulfate (E3-S); estrone beta-D-glucuronide (E1-G); beta-estradiol 17-(beta-D)
      glucuronide (E2-G); estriol 3-(beta-D)-glucuronide (E3-G); beta-estradiol 3
      sulfate 17-glucuronide (E2-SandG); and estradiol 3,17-disulfate (E2-diS). The
      detection limits of this method ranged from 0.1 to 1.4 ng/l. The recovery
      efficiencies of the estrogens in the analysis from influent and effluent of the
      secondary settling tank in a wastewater treatment plant (WWTP) were higher than
      94% for the free estrogens, but were less than 50% for the conjugated estrogens.
      The field study using this method was conducted at twenty WWTPs in Japan. The
      median concentrations of the estrogens ranged from ND to as high as >100 ng/l. In
      the influent and secondary effluent samples, the concentrations of E1, E2 and E3
      were the same levels as those previously reported. We found that the conjugated
      estrogens exist at higher concentrations in the influent and the secondary
      effluent than in the other studies, and that the concentrations of the conjugated
      estrogens were higher than those of the free estrogens.

PMID- 15499676
TI  - A 66-year-old Thai man with fever and abdominal pain.

PMID- 15499677
TI  - Detour behavior in the Quokka (Setonix brachyurus).
AB  - Four quokkas (Setonix brachyurus) were tested in their natural environment for
      the ability to progress around a barrier to a desired goal object (food).
      Symmetrical and asymmetrical barriers were used with different lengths of side
      arm. Three quokkas showed significant tendencies to progress either left or right
      around the barrier, though this laterality declined as the length of the side arm
      of the barrier was extended. One quokka showed no behavioral laterality and this
      animal was also the only one to show spatial reasoning (spontaneous selection of
      the shorter route on first presentation of the asymmetrical barrier) as opposed
      to spatial learning (progressive improvement in choice of the shorter route with
      repeated experience).

PMID- 15499678
TI  - Regulatory mechanisms underlying novelty-induced grooming in the laboratory rat.
AB  - Bouts of pelage cleaning can be readily evoked in laboratory rodents under
      conditions of exposure to novelty. Such novelty-induced grooming is described as
      stereotyped and rostro-caudal in its progression. The patterned structure of
      novelty-induced grooming makes it particularly attractive for research on the
      organizational and motivational underpinnings of co-ordinated behaviour. Micro
      characteristics of stereotyped novelty-induced grooming bouts were studied in 27
      female Wistar rats that were exposed to a novel arena with shelters for a period
      of 15 min. The order of grooming acts within the initial bouts was rostro-caudal,
      but subsequent bouts became progressively disorganized in their sequencing. The
      observed pattern of progressive bout disorganization may be attributed to the
      gradual dearousal from stress. Differences between consecutive bouts in their
      micro-characteristics suggest that at least some grooming actions emitted within
      the context of those bouts operate as relatively independent units of behaviour.
      Those unitary component actions appear to be integrated into protracted pelage
      cleaning sequences by a separate mechanism. Similar endogenous mechanisms have
      been proposed for other co-ordinated motor actions, which suggests that the
      organizational principles identified in the context of novelty-induced grooming
      may represent general principles that govern co-ordinated behaviour.

PMID- 15499679
TI  - Reduced parental effort in relation to laying date in house sparrows (Passer
      domesticus): a study under controlled conditions.
AB  - It is known that breeding success in birds declines with an advance in the laying
      date. In this paper, breeding success diminished with laying date in a house
      sparrow (Passer domesticus) population breeding in captivity. The principal cause
      of the cline in breeding success with date was a decrease in the female feeding
      rate. The parental effort in females decreased with the advance of the laying
      date, although food access was ad libitum throughout the breeding season.
      Consequently, this cline in breeding success may be due to a reduced parental
      investment with the advance of the laying date or to exhaustion due to previous
      reproductive events in the season. Hypotheses usually used to explain the cline
      in breeding success with date can not explain results in this study.

PMID- 15499680
TI  - Serial order of conditional stimuli as a discriminative cue for Pavlovian
      conditioning.
AB  - The serial order in which events occur can be a signal for different outcomes and
      therefore might be a determinant of how an animal should respond. In this report,
      we propose a novel design for studying serial order learning in Pavlovian
      conditioning. In both Experiments 1a and 1b, hungry rats were trained with
      successively presented pairs of auditory and visual stimuli (e.g., A --> B) using
      four different stimuli (A-D). Four orders were paired with food (A --> B, B -->
      C, C --> D, D --> A) while the reversals were extinguished (B --> A, C --> B, D -
      > C, A --> D). An analysis of responding from the second element of each pair
      showed that the rats discriminated trial types that preceded food from those that
      did not. A replication of the effect using a completely counterbalanced design is
      described in Experiment 1b. These results suggest that rats can use the serial or
      temporal order of two sequentially presented non-overlapping elements as the
      basis for discrimination. Two associative accounts are suggested as possible
      mechanisms for solving the discrimination.

PMID- 15499681
TI  - Executive function is less sensitive to estradiol than spatial memory:
      performance on an analog of the card sorting test in ovariectomized aged rhesus
      monkeys.
AB  - Functions supported by the frontal lobes are particularly sensitive to the
      detrimental effects of aging. Recent studies on postmenopausal women find that
      estrogen replacement therapy benefits performance on tasks dependent on the
      frontal lobes. To determine whether estrogen has a similar influence in a rhesus
      monkey model of menopause, we tested five aged, long-term ovariectomized rhesus
      monkeys in a modified version of the Wisconsin Card Sort test which had been
      adapted to the nonhuman primate. In this test, monkeys had to select 3-D objects
      based either on color (blue, red, yellow) or shape (block, tube, cup) and had to
      be able to switch their response as a function of reinforcement contingencies.
      The monkeys were treated with placebo and ethinyl estradiol (EE2, 450 ng/kg/day)
      in alternation with each successive test. Contrary to our hypothesis, estradiol
      treatment did not affect performance. Because previous studies in the same
      monkeys [Neurobiol. Aging 23 (2002) 589] had shown that EE2 improves performance
      on a spatial memory task dependent on the hippocampus, but not on another task
      dependent upon the frontal lobes (the delayed response), we conclude that
      executive processes may be less sensitive to the effects of estradiol than
      hippocampal-dependent tasks.

PMID- 15499682
TI  - Medicare program; home health prospective payment system rate update for calendar
      year 2005. Final rule.
AB  - This final rule sets forth an update to the 60-day national episode rates and the
      national per-visit amounts under the Medicare prospective payment system for home
      health agencies. As part of this final rule, we are also rebasing and revising
      the home health market basket to ensure it continues to adequately reflect the
      price changes of efficiently providing home health services. In addition, we are
      revising the fixed dollar loss ratio, which is used in the calculation of outlier
      payments. This final rule will be the first update of the home health prospective
      payment system (HH PPS) rates on a calendar year update cycle. HH PPS was moved
      to a calendar year update cycle as a result of the provisions of the Medicare
      Prescription Drug, Improvement, and Modernization Act of 2003.

PMID- 15499683
TI  - West Nile Virus Activity--United States, October 13-19, 2004.
AB  - During October 13-19, a total of 200 cases of human West Nile virus (WNV) illness
      were reported from 20 states (Arizona, Arkansas, California, Colorado, Illinois,
      Indiana, Iowa, Kansas, Maryland, Michigan, Mississippi, Missouri, Nevada, New
      Mexico, North Carolina, Oklahoma, Pennsylvania, South Dakota, Wisconsin, and
      Wyoming).

PMID- 15499684
TI  - A mad house transformed: the lives and work of Charles James Beverly FRS (1788
      1868) and John Warburton MD FRS (1795-1847).
AB  - Bethnal Green Asylum was the most notorious of the scandalous early nineteenth
      century private madhouses exposed in two parliamentary Select Committees of
      1815/16 and 1827. From being vilified as the worst asylum in the country, this
      huge and important institution was transformed over 15 years into one of the best
      by two determined men, both Fellows of The Royal Society, John Warburton MD, the
      proprietor, and Charles James Beverly, the medical superintendent, former naval
      surgeon, naturalist and Arctic explorer. This paper describes their hitherto
      unrecorded biographies.

PMID- 15499685
TI  - Medicine supply at the Kongsberg silver mine in Norway before 1805.

PMID- 15499686
TI  - HIV-host interactions: vital to the virus and key to its inhibition.
AB  - Much progress has been made in recent years in the investigation of the interplay
      between HIV-1 and its host cells. Most of these interactions are complex and have
      not yet been fully unraveled. Nevertheless, current knowledge on the molecular
      interactions between HIV and host-cell factors has substantially broadened our
      understanding of the viral life cycle and opened new investigative areas for drug
      intervention.

PMID- 15499687
TI  - The struggle for epistemic authority.

PMID- 15499688
TI  - What did randomised clinical trials do to clinical science?

PMID- 15499689
TI  - Drug therapy in the official danish plague instructions, 1619-1709.

PMID- 15499690
TI  - Early British psychoanalysis and the Medico-Psychological Clinic.

PMID- 15499691
TI  - Dung, sludge, and landfill: biogas technology in the Netherlands, 1970-2000.

PMID- 15499692
TI  - In Pursuit of standardization: the British ministry of health's model 8F
      wheelchair, 1948-1962.

PMID- 15499693
TI  - Factor II gene(prothrombin G20210A)mutation and neonatal cerebrovenous
      thrombosis.

PMID- 15499694
TI  - Fluvoxamine: new indication. No progress in obsessive-compulsive disorder.
AB  - (1) Four drugs are approved in France for patients with obsessive-compulsive
      disorders, namely clomipramine and three selective serotonin reuptake inhibitors
      (SSRIs): fluoxetine, paroxetine and sertraline. None of the four has emerged as a
      reference treatment. For children with obsessive-compulsive disorder, the
      treatment hierarchy is as follows: psychotherapy; behaviour therapy;
      clomipramine; sertraline. (2) Fluvoxamine, another SSRI, has now been approved in
      France for the treatment of obsessive-compulsive disorder in patients aged at
      least 8 years, after European harmonisation of SPCs for fluvoxamine-based
      preparations. (3) In adults, two placebo-controlled trials and the six trials
      versus clomipramine show that fluvoxamine, like clomipramine, is only partially
      effective (about one-third of patients "respond"). (4) In the only placebo
      controlled trial in 120 children and adolescents aged from 8 to 17 years, who
      were treated for 10 weeks, efficacy was even more modest (response rate 15%,
      compared to 10% with placebo). (5) The safety profile of fluvoxamine is the same
      as that of all SSRIs but it has a potential for more drug interactions. (6) In
      practice, approval of fluvoxamine in adults or children with obsessive-compulsive
      disorder will have no impact on their management.

PMID- 15499695
TI  - Topiramate: new indication. Single-agent therapy in refractory epilepsy: for a
      few patients only.
AB  - (1) Topiramate is helpful for some adults and children (aged over 4 years) with
      partial or generalised epilepsy, when combined with an inadequate ongoing
      treatment. (2) The indications for topiramate have now been extended in France to
      cover single-agent therapy of refractory epilepsy, from the age of 2 years. (3) A
      dose-finding study of 48 patients with refractory partial epilepsy suggests that
      the efficacy of topiramate monotherapy is dose-dependent. In a non comparative
      trial in 170 patients with refractory partial or generalised epilepsy, 12
      patients were able to switch to topiramate alone after a phase of combining
      topiramate with their ongoing treatment. (4) The licence extension to children
      over 2 years of age is based solely on the results of previous trials. (5) Two
      dose-finding studies, and a trial versus a standard antiepileptic in which
      topiramate was used alone, confirmed that the safety profile of topiramate is
      similar to that of other antiepileptics, neuropsychological disturbance
      predominating. (6) Other adverse effects more specific to topiramate include
      cognitive and language problems, weight loss and reduced appetite, acute myopias
      sometimes associated with intraocular hypertension, an increased risk of renal
      lithiasis, reduced sweating with a risk of hyperthermia, and metabolic acidosis.
      (7) In practice, some patients whose epilepsy is refractory to an optimally
      administered treatment may improve when topiramate is added; and a small minority
      of them can gradually discontinue their previous treatment.

PMID- 15499696
TI  - Gefitinib: new preparation. Non small-cell lung cancer: stricter assessment
      needed.
AB  - (1) Platinum-based chemotherapy is generally used to treat advanced-stage non
      small-cell lung cancer (stages III and IV), but has only a modest impact on
      survival. There is no reference treatment. (2) Gefitinib inhibits the tyrosine
      kinase activity of the receptor for EGF (epidermal growth factor), which is
      thought to be involved in tumour growth. It has a temporary licence in France and
      is used on a named-patient basis, but full marketing authorisation has already
      been granted in Japan, the United States, and elsewhere. (3) Two double-blind
      dose-finding studies compared two doses of oral gefitinib monotherapy (250 mg/day
      and 500 mg/day) in patients in whom at least two lines of chemotherapy had
      failed. The results were favourable, with a median survival of 6 months and a
      symptomatic improvement in some patients, but they are undermined by the absence
      of a placebo group and by major protocol violations. (4) Two double-blind trials,
      each in more than 1000 patients, showed that gefitinib does not increase the
      efficacy of first-line platinum combinations. (5) About 15% of patients receiving
      gefitinib monotherapy in clinical trials stopped taking the treatment because of
      adverse events. The most frequent were gastrointestinal (diarrhea, nausea,
      vomiting) and cutaneous (rash, acne, dry skin, pruritus). (6) Interstitial
      pneumonitis occurred in about 1% of patients, and was fatal in about one-third of
      cases. (7) Gefitinib is metabolised by the cytochrome P450 isoenzyme CYP3A4, so
      carries a potentially high risk of interactions. (8) In practice, more thorough
      assessment of gefitinib is needed to determine whether this new drug is
      beneficial for patients with non small-cell lung cancer. Marketing authorisation
      is not currently justified.

PMID- 15499697
TI  - Adalimumab: new preparation. Rheumatoid arthritis: no therapeutic advance.
AB  - (1) There is no agreed treatment for patients with rheumatoid arthritis in whom
      first-line options, including methotrexate, have failed. Recent slow-acting
      antirheumatic drugs have not been compared with one another, but they seem to
      have similar risk-benefit ratios. Etanercept, a TNF-alpha antagonist, is the most
      convenient to use. (2) Adalimumab is the third TNF-alpha antagonist to be
      marketed in France for use in rheumatoid arthritis, after etanercept and
      infliximab. (3) The clinical evaluation dossier mentions no data from comparative
      trials with other slow-acting antirheumatic drugs used in refractory rheumatoid
      arthritis. (4) Placebo-controlled trials show that adalimumab alone has very
      modest efficacy. The best results are obtained when adalimumab is combined with
      methotrexate. On the basis of the least demanding criterion (ACR 20%), about two
      third of patients are improved by this combination. (5) Clinical trials show that
      it is pointless to continue treatment with adalimumab for more than three months
      if efficacy is inadequate. (6) Adalimumab, like other TNF-alpha antagonists, can
      have potentially serious adverse effects, linked mainly to its immunosuppressive
      action. Opportunistic infections and cases of tuberculosis have been reported,
      even during short treatment periods. Many questions remain regarding long-term
      treatment effects, such as the risk of lymphoma, autoimmune disorders, and onset
      or aggravation of demyelinising diseases. (7) Adalimumab is given once every two
      weeks, subcutaneously, while etanercept 25 mg is given as two subcutaneous
      injections per week, and infliximab is given as an intravenous infusion every 8
      weeks. (8) In practice, for patients with rheumatoid arthritis who do not respond
      to methotrexate and to other classical slow-acting antirheumatic drugs,
      etanercept is the best choice among recent slow-acting antirheumatic drugs.

PMID- 15499698
TI  - Ezetimibe: new preparation. A cholesterol-lowering drug with no clinical
      advantage.
AB  - (1) Simvastatin and pravastatin are the drugs of choice for secondary or primary
      prevention of cardiovascular events in patients with hypercholesterolaemia. Both
      these statins have proven clinical efficacy. If statin therapy is inadequate, the
      dose can be increased or a drug combination can be tried, while keeping a lookout
      for adverse effects. (2) Ezetimibe is a cholesterol-lowering drug that is said to
      inhibit intestinal absorption of cholesterol and related phytosterols, while not
      affecting the uptake of other nutrients (unlike resins). (3) The clinical
      evaluation dossier contains no data from trials with relevant morbidity or
      mortality endpoints. Primary and secondary prevention were not studied
      separately. (4) In patients with hypercholesterolaemia, two placebo-controlled
      trials show that ezetimibe reduces total cholesterol concentration (by about
      13%), and LDL-cholesterol (by about 18%). Its effects on HDL-cholesterol and
      triglyceride levels are at best moderate. It is not known whether these effects
      reduce mortality or prevent cardiovascular events. (5) Four trials tested initial
      combination therapy with a statin plus ezetimibe, in comparison with statin alone
      and ezetimibe alone. They showed an additive effect of the two drugs on LDL
      cholesterol levels. Ezetimibe alone was no better than statin monotherapy. (6) A
      trial in patients who did not respond adequately to statin monotherapy showed
      that adding ezetimibe increased the number of patients whose LDL cholesterol
      level fell to a predetermined cutoff point. But the clinical relevance of this
      result is unknown. Two other trials have shown that, in this setting, adding
      ezetimibe to simvastatin or to atorvastatin increased the number of patients who
      reached the LDL-cholesterol cutoff relative to continued statin monotherapy at a
      higher dose. (7) In homozygous familial hypercholesterolaemia, high-dose statin
      and ezetimibe combination therapy reduced the LDL-cholesterol more effectively
      than high-dose statin alone. It is not known whether adding ezetimibe is more
      effective than LDL apheresis alone. (8) In homozygous familial sitosterolaemia, a
      very rare disorder due to increased absorption of dietary cholesterol and
      phytosterols, a placebo-controlled trial showed that ezetimibe had no significant
      impact on the absolute sitosterol value. (9) Comparative trials reported no major
      adverse effects associated with ezetimibe, but their duration (maximum three
      months) is too short to rule out long-term adverse effects. Initial
      pharmacovigilance reports cases of muscular and hepatic adverse effects. (10) In
      practice, ezetimibe has discernible effects in the laboratory. But the absence of
      data based on clinical endpoints and trials versus other cholesterol-lowering
      drugs with proven clinical benefits, together with the lack of information on
      possible long-term adverse effects, means ezetimibe must be evaluated more
      thoroughly before it can be recommended for routine use.

PMID- 15499699
TI  - Tenofovir: new indication. For first-line antiretroviral therapy: wait and see.
AB  - (1) First-line antiretroviral combinations generally include, in addition to a
      protease inhibitor or a non nucleoside reverse transcriptase inhibitor, two
      nucleoside reverse transcriptase inhibitors, namely zidovudine + didanosine,
      stavudine + lamivudine, or zidovudine + lamivudine. (2) Tenofovir disoproxil
      (referred to simply as tenofovir below) is a nucleotide HIV reverse transcriptase
      inhibitor. Previously recommended for second-line treatment in case of
      virological failure, it is now approved for first-line therapy in adults. (3)
      This licence extension is based on a double-blind trial comparing tenofovir +
      lamivudine + efavirenz with stavudine + lamivudine + efavirenz in 602 patients.
      After 96 weeks, three-quarters of patients had undetectable viral load (<50
      copies/ml), and there was no statistically significant difference among the
      groups. (4) The number of serious adverse effects was similar in the two groups.
      Relative to the stavudine combinations, there were fewer reports of lipodystrophy
      (1% versus 12%), fewer peripheral neuropathies (3% versus 10%) and fewer
      prescriptions of lipid-lowering therapy (2% versus 10%) among patients taking
      tenofovir. Tenofovir seemed to have a worse effect on renal function and bone
      metabolism, however. (5) Tenofovir is taken only once a day, but so are
      didanosine and lamivudine. (6) In practice, there is not yet enough evidence to
      support the routine use of tenofovir in first-line antiretroviral combinations.
      Tenofovir is, however, an interesting alternative when stavudine is poorly
      tolerated.

PMID- 15499700
TI  - Fluoroquinolones in children: poorly defined risk of joint damage.
AB  - (1) Rare but well-documented cases of joint damage, with no other identified
      cause, have been reported in children treated with systemic fluoroquinolones. The
      joint damage usually resolves gradually after drug withdrawal and are more
      frequent with pefloxacin. (2) The few available paediatric trials included too
      few patients to identify rare adverse effects on joints, or to show a causal
      relationship between treatment and joint damage. (3) In practice, quinolones are
      an option for children only when the expected benefit outweighs the risk of joint
      damage. In the rare cases in which fluoroquinolone therapy is justified,
      ciprofloxacin is the drug of first choice. Pefloxacin should be avoided.

PMID- 15499701
TI  - Metabolic acidosis due to topiramate.
AB  - (1) Topiramate carries a dose-dependent risk of severe metabolic acidosis in
      adults and children. (2) Various situations increase the risk, including
      diarrhea, respiratory disorders and surgery. (3) Loss of appetite, fatigue and
      hyperventilation are warning signs.

PMID- 15499702
TI  - St John's wort and depression: slight efficacy at best, many drug interactions.
AB  - (1) St John's wort has been widely used for centuries as a herbal remedy. Dozens
      of trials, of variable quality, have examined the therapeutic value of St John's
      wort. Published meta-analyses show that St John's wort extracts are more
      effective than placebo in patients with mild and moderate depression. (2) Trials
      show that St John's wort is about as effective as tricyclic and serotonin
      reuptake inhibitor antidepressants. (3) There is insufficient evidence to
      determine the efficacy of St John's wort in patients with more severe depression.
      (4) Few, mostly minor adverse effects have been reported, but there may be a
      small risk of serotonin syndrome and cutaneous photosensitisation. (5) Some
      components of St John's wort interfere with CYP3A4, one of the main cytochrome
      P450 isoenzymes. CYP3A4 is involved in the metabolism of many commonly used
      drugs. St John's wort reduces the efficacy of several drug groups including:
      immunosuppressants (risk of graft rejection), oral contraceptives (risk of
      pregnancy), oral anticoagulants (risk of thrombosis), and HIV protease
      inhibitors. It can also reduce the bioavailability of digoxin. (6) In practice,
      St John's wort is an inappropriate treatment for severe depression. It is,
      however, an acceptable option for short-term management of transient depressed
      mood when there is no risk of drug interactions and when the patient is properly
      informed of this risk. (7) In short, the risk-benefit balance of St John's wort
      is no better than that of standard antidepressants, mainly because of the risk of
      drug interactions.

PMID- 15499703
TI  - HDL cholesterol: metabolic pathways and drug developments. Fifth Annual
      International Conference of the Knowledge Foundation. March 8-9, 2004, Cambridge,
      MA, USA.

PMID- 15499704
TI  - Use of abciximab in massive pulmonary embolism with free-floating, intra-cardiac
      thrombi.

PMID- 15499705
TI  - Worsening of thrombotic thromboctyopenic purpura symptoms associated with
      desmopressin administration.

PMID- 15499706
TI  - The impact of the Master Settlement Agreement on cigarette consumption.
AB  - In 1998, 46 states and the four major tobacco companies signed the Master
      Settlement Agreement (MSA), which stipulated that the tobacco companies pay
      states $206 billion over 25 years and take steps to reduce youth smoking. The
      remaining states settled separately. We sought to determine the effect of the
      settlements on demand for cigarettes. Using a nationwide sample from 1990 to
      2002, we estimated a model of the decision to smoke cigarettes. The settlements
      affected smoking primarily through price increases for cigarettes, although there
      was evidence that other policy instruments influenced smoking rates for younger
      smokers. By 2002, the settlements had reduced overall smoking rates by 13 percent
      for ages 18 to 20 and older than 65 and 5 percent for ages 21 to 64.

PMID- 15499707
TI  - Federal policy mandating safer cigarettes: a hypothetical simulation of the
      anticipated population health gains or losses.
AB  - If manufacturing a safer cigarette is technically possible--an open question-
      then mandating that tobacco manufacturers improve the safety of cigarettes would
      likely have both positive and negative implications for the nation's health. On
      the one hand, removing toxins may reduce the incidence of smoking-related
      diseases and premature mortality in smokers. On the other hand, smokers might be
      less inclined to quit, those who have quit might resume the habit, and youth who
      have never smoked will have one less reason to avoid tobacco use. To assess the
      expected population health impacts of a legislative or regulatory mandate, we
      created the Tobacco Policy Model, a system dynamics computer simulation model.
      The model relies on secondary data and simulates the U.S. population over time
      spans as long as 50 years. Our simulation results reveal that even if requiring
      cigarettes to be safer makes smoking more attractive and increases tobacco use, a
      net gain in population health is still possible.

PMID- 15499708
TI  - Are Colombian sickness funds cream skimming enrollees? An analysis with
      suggestions for policy improvement.
AB  - One of the primary objectives of Colombian social health insurance reform was to
      increase competition among for-profit insurers. Unfortunately, the flat capitated
      formula creates an opportunity for sickness funds to maximize reimbursement gains
      by cream skimming--selecting against unhealthy individuals. This paper explores
      sickness fund selection behavior to evaluate the efficiency losses associated
      with the introduction of managed competition in Colombia. Data from a 1997
      Colombian household survey are analyzed with a bivariate probit model with
      partial observability using instrumental variables. The model yields some
      evidence of sickness fund selection based on health status. Public policy options
      to discourage risk selection by health status are discussed.

PMID- 15499709
TI  - Abortion laws in the states.

PMID- 15499710
TI  - A crisis business can't ignore.

PMID- 15499711
TI  - Effectiveness of the MASTER program for teaching special children multiplication
      and division.
AB  - In this study, the utility of a MAthematics Strategy Training for Educational
      Remediation (MASTER) program, (Van Luit, Kaskens, & Van der Krol, 1993) was
      examined. The effectiveness of the program, designed to encourage strategy
      utilization with multiplication and division problems, was investigated for 84
      students with poor mathematics skills, some of whom had learning disabilities (n
      = 42) and others with mild levels of mental retardation (n = 42). The results
      showed that the use of the self-instruction program resulted in significant
      improvement over the general instruction program. Furthermore, far transfer was
      found for the children with learning disabilities in the experimental group when
      they used effective problem-solving strategies on nontrained tasks. The results
      are consistent with previous findings suggesting the importance of self
      instruction in mathematics training programs.

PMID- 15499712
TI  - Stability of arithmetic disability subtypes.
AB  - Cross-sectional research has identified subtypes of children with learning
      disabilities who may have distinctive cognitive ability patterns. This study
      examined the stability over 19 months of academic subtyping classifications for
      80 children ages 9 to 13 representing four subtypes of arithmetic disabilities
      (AD), using three criteria for learning disability identification. Approximately
      half of the sample retained AD regardless of identification method. Children with
      pervasive deficits in arithmetic, reading, and spelling displayed the greatest
      subtype stability. Only one third of the children with the other subtypes,
      including those with isolated arithmetic deficits, retained their original
      subtypes. Thus, drawing conclusions and making recommendations based on academic
      subtyping at a single point in time may be unwise.

PMID- 15499713
TI  - Not all reading disabilities are alike.
AB  - In this article, reading disability is defined broadly to refer to below-average
      achievement in reading comprehension as assessed by a standardized test. With our
      research we tried to answer the question of whether all children with reading
      disability share a common etiology of deficient phonology, or constitute
      heterogeneous groups. The answer to this question was sought in four studies that
      examined reading disabilities from the perspective of componential skills of
      reading. In Part 1, the results of the first study are reported. A principal
      components analysis of the performance of 139 children from Grades 3, 4, and 6 on
      reading-related tasks yielded two factors: decoding and comprehension. However,
      factor analyses conducted for each grade separately indicated that orthographic
      skill and processing speed could possibly constitute a third component. The
      orthography-speed factor emerged as a factor only in the 6th grade. Part 2 of
      this article reports the findings of three studies that analyzed the componential
      skills profiles of poor readers. It was found that the poor readers constituted
      heterogeneous groups and that four different types of poor readers could be
      identified with deficiency in any one of the following skills: (a) decoding only,
      (b) comprehension only, (c) a combination of decoding and comprehension, and (d)
      a combination of orthographic processing and reading speed. It was also found
      that the criteria used in selecting poor readers influenced the distribution of
      the ratio of the four types of poor readers within any given group.

PMID- 15499714
TI  - Reading disability defined as a discrepancy between listening and reading
      comprehension: a longitudinal study of stability, gender differences, and
      prevalence.
AB  - The purpose of this study was to determine whether defining reading disability by
      a discrepancy between group-administered tests of listening and reading
      comprehension would produce result similar in terms of stability, gender ratio,
      and prevalence to IQ-achievement test discrepancy definitions. The total
      population of a small school district (N = 1,008) was followed from
      prekindergarten through Grade 7-8 for 13 years. As is often seen in
      epidemiological studies using IQ and individually administered reading tests to
      define reading disability, stability in the classification of reading disability
      was low. Among the participants with a consistent reading disability, the male-to
      female ratio was 3.2:1, compared with 1.3:1 for the 5.1% of the sample who were
      nondiscrepant poor readers in both lower and upper grades. A mean 2.7% of the
      population was classified as reading disabled over the eight-grade span, and only
      1.7% demonstrated a consistent reading disability in both the lower and the upper
      grades. An increase in the ratio of nondiscrepant to discrepant poor readers
      after Grade 5 was due mainly to late-emerging poor readers. It was concluded that
      defining reading comprehension disability in terms of a discrepancy between
      listening and reading comprehension provides a fairly accurate estimate of the
      stability, gender ratio, and prevalence of the disorder.

PMID- 15499715
TI  - Central auditory processing ability in children with ADHD with and without
      learning disabilities.
AB  - A few studies have shown more central auditory processing deficits in children
      with attention-deficit/hyperactivity disorder (ADHD) than in nondisabled
      children. Because these studies failed to screen participants with ADHD for
      learning disabilities (LD), it is not clear whether these deficits are correlates
      of ADHD or LD or both. In the present study, the central auditory processing
      ability of children with ADHD, ADHD with LD, and no disabilities was examined.
      Results indicated lower central auditory processing ability, and significant
      correlations between reading and ADHD symptoms and reading and central auditory
      processing ability in the ADHD with LD group compared with the other two groups.
      These findings suggest that central auditory processing deficits are more likely
      to be associated with LD than ADHD.

PMID- 15499716
TI  - Neuropsychological and behavioral assessment of ADHD in seven- to twelve-year-old
      children: a discriminant analysis.
AB  - We hypothesized that children with attention-deficit/hyperactivity disorder
      (ADHD) would underperform on neuropsychological tests that are sensitive to
      executive function impairments. We further proposed that a linear discriminant
      analysis using behavioral and neuropsychological variables as dependent variables
      would pinpoint the capability of behavioral questionnaires and neuropsychological
      tests to predict the correct classification of ADHD and control children. We
      designed a transversal study with 62 seven- to twelve-year-old children with ADHD
      and 62 Full Scale IQ-matched controls using two behavioral scales and 13
      neuropsychological tests. Using analysis of variance and covariance with age and
      school achievement and multifactor analysis of variance, we found that behavioral
      variables established robust, statistically significant differences between
      groups (p < .001). Children with ADHD scored worse than controls on 31 out of 61
      neuropsychological variables. Children with ADHD, however, obtained better scores
      that were statistically significant on WISC-R Comprehension and Picture
      completion. A linear discriminant analysis with nine behavioral variables
      correctly classified 100% of the participants in both groups. Another linear
      discriminant analysis using 10 neuropsychological variables correctly classified
      85.48% of the participants in both groups. We propose a core battery of selected
      tests for assessing children with ADHD. The significance of cross-cultural
      analyses of different developmental disturbances is emphasized.

PMID- 15499717
TI  - The balance model of dyslexia and remedial training: an evaluative study.
AB  - The aim of this study was to test the validity of Bakker's (1983, 1990) theory
      and treatment paradigm of dyslexia. Twenty-one children (mean age = 9.9 years)
      categorized as P-type dyslexics (showing accurate but slow and fragmented
      reading) and 19 children (mean age = 9.7 years) categorized as L-type dyslexics
      (fast but inaccurate readers) were presented with hemisphere-specific stimulation
      (HSS) and hemisphere-alluding stimulation (HAS). HSS was produced by presenting
      words to either the left or the right visual half-field, or to the left or right
      hand of the participant. HAS training was achieved through the presentation of
      either semantically/phonetically demanding or perceptually demanding text.
      Participants were given either a treatment program that was specifically designed
      for their particular dyslexia subtype, or a program that had been deliberately
      chosen to be inconsistent with their subtype. Contrary to predictions,
      participants made gains on all of the reading measures, regardless of the type of
      treatment given. On the basis of these findings it is suggested that treatment
      gains made are due to nonspecific training effects and not to the specific nature
      of Bakker's remedial strategies.

PMID- 15499718
TI  - The changes of quality of life in the patients after phacoemulsification with
      intraocular lens implantation.
AB  - PURPOSE: To investigate the improvement and maintenance of the quality of life in
      the patients after phacoemulsification with intraocular lens implantation.
      METHODS: The study population consisted of 116 patients receiving
      phacoemulsification with intraocular lens implantation. They were interviewed
      using the quality of life questionnaire, and the clinical outcomes were evaluated
      before surgery and at 1 week, 1 month, 3 months, 6 months after surgery
      respectively. RESULTS: Patients reported similar scores of quality of life and
      all the four subscales among 1-week , 1-month, 3-month and 6-month follow-up
      visit after surgery, all of which were higher than the scores before surgery.
      CONCLUSION: Patients receiving phacoemulsification reported rapid improvement in
      quality of life after surgery, and the quality of life scores were not changed
      significantly from 1 week to 6 months after surgery.

PMID- 15499719
TI  - The treatment of Terrien marginal degeneration using lamellar keratoplasty with
      dried corneosclera.
AB  - PURPOSE: To treat the Terrien marginal degeneration using lamellar keratoplasty
      with dried corneosclera and evaluate the clinical effect of this operation.
      METHODS: The study included 78 cases with Terrien marginal degeneration who
      underwent the lamellar keratoplasty with dried corneosclera. Among them, 48 cases
      in experiment I group and 30 cases in experiment II group underwent lamellar
      keratoplasty with glycerin-preserved corneosclera and anhydrous calcium chloride
      storeded corneosclera respectively. All the patients were followed-up from 6
      months to 10 years. The control group consisted of 38 cases with Terrien marginal
      degeneration electively undergoing lamellar keratoplasty with fresh corneosclera
      simultaneously. RESULTS: The area of the corneal thinning was mended and the
      eyeball was saved. The corneal astigmatism of the patients was corrected
      obviously. The patient's vision was improved significantly. No recurrence and
      rejection were observed after the operation. There is no significant difference
      between the experiment group (experiment I group or experiment II group) and
      control group. (P > 0.05), despite longer duration of postoperative corneal edema
      in experiment group. CONCLUSIONS: The lamellar keratoplasty with dried
      corneosclera for treatment of Terrien marginal degeneration is a safe and
      effective operation. It is an alternative to lamellar keratoplasty with fresh
      corneosclera for treatment of Terrien marginal degeneration. It is suitable to be
      popularized in the local hospital of our country.

PMID- 15499720
TI  - The clinical analysis of endogenous endophthalmitis.
AB  - PURPOSE: To study the clinical characteristics, therapeutic efficacy and
      investigate prognostic factors of endogenous endophthalmitis. METHODS: Twenty
      eight cases (28 eyes) of endogenous endophthalmitis were surveyed
      retrospectively. The clinical characteristics, primary infection foci,
      predisposing systemic disease, complications, pathogens examination, therapeutic
      options and efficacy were analysed. RESULTS: The endogenous endophthalmitis
      occurred more frequently in the right eye than in the left one. The respiratory
      tract was the most common primary foci. The positive rate of pathogens culture
      was higher in vitreous sample than that in other tissues. Cataract and retinal
      detachment were the common complications. The visual improvement and infection
      control were achieved in 13 eyes (46.43%). These 13 patients received treatment
      (3.77 +/- 2.49) days after onset of endophthalmitis being much earlier than that
      of others [(10.13 +/- 4.98) days, P = 0.002]. The prognosis was relevant to the
      type of the disease. The anterior segment inflammation type (anterior type) had
      better prognosis than posterior segment inflammation type (posterior type) and
      that of inflammation in both parts (mix type) (P < 0.05). There were no
      significant relation between the prognosis and the age, predisposing systemic
      disease, vitreous antibiotic injection and vitrectomy (P > 0.05). CONCLUSIONS:
      Endogenous endophthalmitis is a vital ocular emergency. Early diagnosis and
      effective treatment combination with systemic and local antibiotics are of
      significant value. The anterior type is prone to have better outcome than the
      others.

PMID- 15499721
TI  - Diagnostic ultrasound and pars plana vitrectomy in endophthalmitis.
AB  - PURPOSE: To compare the results by B-scan ultrasonography and findings in pars
      plana vitrectomy, and assess the diagnostic value of B-scan ultrasonography in
      endophthalmitis. METHODS: Thirty eyes of 30 subjects diagnosed as endophthalmitis
      were selected, who undergone preoperative B-scan ultrasonography. The result of
      pars plana vitrectomy was recorded. The above two results were compared. RESULTS:
      On the evaluation of vitreous and retinal states in the patients with
      endophthalmitis, the sensitivity of ultrasound was 90%-100%, and the specificity
      was 79%-100%. Poorer preoperative visual acuity was related with retinal
      detachment and retinal dissolution. The preoperative visual acuity in eyes with
      local vitreous opacity was better than with diffuse vitreous opacity. CONCLUSION:
      Comparison of the results of B-scan ultrasonography and the findings in pars
      plana vitrectomy showed B-scan ultrasonography is highly sensitive, specific, and
      is very helpful in the evaluation of endophthalmitis. B-scan ultrasonography can
      not only supply much information in the diagnosis of endophthalmitis but also
      inspect its trends and changes, which is helpful in the selection of treatment
      and planning the time of surgery.

PMID- 15499722
TI  - Clinic analysis of Behcet disease.
AB  - PURPOSE: To analyze the clinic manifestation and prognosis of Behcet disease.
      METHOD: Twenty patients requiring inpatient treatment with Behcet disease were
      retrospectively analyzed. RESULTS: The morbidity of Behcet disease is 5.5/100
      000. In the systemic damage, stomatocace and skin lesion are 95%, eye lesion and
      genital ulcer 50%, joint lesion 45%, gastrointestinal lesion 35%, Uveitis is the
      major disease in eye lesion, and followed in order by retinal vasculitis and
      obstruction of retinal artery. Attack age average 30.3 years old. Diagnosis age
      average 34.8 years old. The patients stay in hospital for 41 days on the average.
      Cure rate is 55%, improvement rate 40%, blinding rate of eye lesion is 36%.
      CONCLUSIONS: Behcet disease is a multisystem lesion disease. Stomatocace and skin
      lesion is the major lesion, the next in common occurrence are eye and genital
      lesions. Repeated attack of uveitis, complicated cataract and secondary glaucoma
      are the major causes of blindness.

PMID- 15499723
TI  - Photodynamic therapy for age-related macular degeneration.
AB  - PURPOSE: To evaluate short-term effects of single photodynamic therapy (PDT) for
      age-related macular degeneration (AMD) accompanied with choroidal
      neovascularization (CNV). METHODS: We analyzed retrospectively the effects of
      single PDT for 20 patients (20 eyes) with CNV caused by AMD. Corrected visual
      acuity, fluorescein angiography (FA) and optic coherence tomography (OCT) were
      examined before and after PDT. All patients were followed up at least 3 months.
      RESULTS: At the end of 3-month follow-up, 5 eyes had vision progress, 15 eyes had
      vision stable and no eye had vision deterioration. Fluorescein angiography one
      week post PDT showed cessation of fluorescein leakage in 8 eyes with predominant
      classic CNV, and reduction of fluorescein leakage in 12 eyes with minimal classic
      CNV or occult CNV without classic component. At the 3-month following PDT
      fluorescein angiography showed fluorescein leakage reappeared in 4 of 8 eyes with
      predominant classic CNV. Among 12 eyes with minimal classic CNV or occult CNV
      without classic component, 9 eyes showed decreased or unchanged fluorescein
      leakage, 3 eyes had a progression of fluorescein leakage. Optic coherence
      tomography showed obvious recovery of serous sensory retinal detachment after
      PDT. CONCLUSION: PDT may occlude or inhibit CNV caused by AMD in short-term. No
      obvious side effects were noticed.

PMID- 15499725
TI  - Sturge-Weber syndrome associated with early diffuse choroidal hemangiaoma: a case
      report.
AB  - PURPOSE: To report indocyanine green angiography (ICGA) findings in one patient
      of diffuse choroidal hemangioma associated with Struge-Weber syndrome. METHODS:
      Color fundus photography, fluorescein angiography (FA) and ICGA were performed in
      a patient with diffuse choroidal hemangioma associated with Sturge-Weber
      syndrome. RESULTS: Three findings were unveiled by ICGA: rapid filling of diffuse
      choroidal hemangio's vascular network in the early stages; diffuse
      hyperfluorescence visual up to the late phase; no "wash-out" phenomenon was
      observed in the late phase. CONCLUSION: Indocyanine green angiography can provide
      information that is not detected by clinical or fluorescence angiographic
      examination in the patient with Sturge-Weber syndrome. ICGA may be important and
      sensitive in detecting the diffuse choroidal hamangioma associated with Sturge
      Weber syndrome.

PMID- 15499724
TI  - Clinical features and surgical treatment of A-pattern exotropia.
AB  - PURPOSE: To investigate the clinical characteristics and determine the effective
      surgical managements of A-pattern exotropia. METHODS: Thirty-two patients with A
      pattern exotropia underwent superior oblique muscle weakening procedures, medial
      rectus resection or (and) lateral rectus recession. Pre- and post-operative eye
      position, deviation angle, superior oblique function and binocular vision were
      examined and analyzed in the cases. RESULTS: Overaction of the superior oblique
      muscles (31/32) and underaction of the medial rectus muscle (20/32) were
      presented in the cases. Postoperatively, a satisfactory ocular alignment was
      obtained in 28 cases (87.5%), and the A-pattern was corrected in 31 cases
      (96.9%). Four cases got binocular vision after surgery. CONCLUSIONS: As one of
      the most common forms of A and V patterns, A-pattern exotropia showed clinical
      characteristics of superior oblique muscle overaction and medial rectus muscle
      underacion, which should be the primary factors in the etiology of A-pattern
      exotropia, and superior oblique weakening procedures combined with horizontal
      surgery should be an effective approach to A-pattern exotropia treatment.

PMID- 15499726
TI  - The protective role of Mecobalamin following optic nerve crush in adult rats.
AB  - PURPOSE: To evaluate the potential for Mecobalamin as a neuroprotective agent in
      optic nerve crush injury. METHODS: Twenty-four adult Sprague-Dawley rats were
      randomly divided into four groups. One group acted as normal controls, while in
      the other three groups the right eye was subjected to optic nerve crush injury.
      Of the three crush injury groups one group received no treatment, while the other
      two groups received intramuscular injections of VitaminB12 or Mecobalamin (10
      microg) immediately after crush injury and then every two days. All the rats were
      sacrificed one month post-treatment, and the eyes attached with optic nerves were
      removed for histology. The morphological changes of optic nerve axons and retinal
      ganglion cells (RGCs) were assessed under light microscope (LM) and transmission
      electromicroscope (TEM). The numbers of axons and RGCs were counted. RESULTS: In
      this study we demonstrate the potential for Mecobalamin as a neuroprotective
      agent following optic nerve crush injury. We show here that the axons of optic
      nerves were loose in structure or destroyed. The mitochondria of the RGCs was
      swollen, and the Nissel body was less evident after the crush injury. Moreover,
      the number of axons and RGCs was significantly reduced (P < 0.001). However,
      these changes were less dramatic after the Mecobalamin-treatment. More axons and
      RGCs were remained in the group than those in the untreated injury group (P =
      0.010 and 0.003 respectively), and those in the VitaminB12-treated group (P =
      0.037 and 0.035 respectively). More significantly, there were newly formed axons
      found in the Mecobalamin-treated group. CONCLUSIONS: Optic nerve crush injury in
      rats causes the loss of the axons and RGCs but this may be ameliorated by
      treatment with Mecobalamin.

PMID- 15499728
TI  - Effect of high dosage of methylprednisolone on rat retinal ganglion cell
      apoptosis after optic nerve crush.
AB  - PURPOSE: To investigate the effect of high dose methylprednisolone (MP) on
      retinal ganglion cells (RGC) apoptosis. METHODS: One hundred and twenty six
      Wistar rats were divided into normal control, crush control and MP treatment
      groups. High dose MP and 0.9% sodium chloride were injected intravenously at 1 h
      after injury in the treatment group and crush control group, respectively.
      Apoptotic cells, Bcl-2 and Bax positive cells were located and calculated by
      terminal-deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling
      (TUNEL), immunohistochemical method and retinal whole-mount combined with section
      technique at day 4, 7, 14 after crush, respectively. RESULTS: The TUNEL-labeling
      cells, Bcl-2 and Bax positive cells were detected in the ganglion cell layer of
      retina. Few apoptotic cells, a few of Bcl-2 and Bax positive cells were observed
      in normal control groups. The numbers of positive cells increased gradually after
      crush. The number of apoptotic cells and Bax positive tells in treatment groups
      was less than that in crush group significantly (P < 0.05), while the number of
      Bcl-2 positive cells in treatment group was more than that in crush group at day
      4, 7 and 14 after crush significantly (P < 0.05). CONCLUSIONS: These results
      suggest that high dose MP can inhibit the apoptosis of RGC after optic nerve
      crush probably through up-regulation of Bcl-2 expression and down-regulation of
      Bax expression.

PMID- 15499727
TI  - Measurement of intraocular concentrations of etoposide after systemic and local
      administration.
AB  - PURPOSE: To determine and compare the concentrations of etoposide achieved in the
      aqueous and vitreous humors after intravenous and subconjunctival administration.
      METHODS: Eight New Zealand rabbits were treated with etoposide (5mg/kg)
      intravenous and etoposide (2.5 mg/ml, 0.5 ml) subconjunctival respectively. The
      samples of the aqueous and vitreous humors of rabbits were drawed at 1, 2, 3
      hours after the end of infusion. The concentrations of the etoposide were
      determined by high-performance liquid chromatography. A Diamonsil TM C18 column (
      6 x 40 mm, 3 microm ) with a mobile phase of 400 ml of methanol and 600 ml of 100
      mmol x L(-1) sodium dihydrogen phosphate with 0.02 mmol x L(-1) dioctyl sodium
      sulfosuccinate and 0.5% triethylanine (pH value was adjusted to 6 by phosphoric
      acid) was used. The detective wavelength was at 235 nm and the flow rate was 1.0
      ml x min(-1). RESULTS: The concentrations of etoposide in aqueous and vitreous
      humors after administrated in intravenous for 1, 2, 3 hours were 38.5, 52.2,
      44.1(ng/ml) and 12.0, 25.1, 18.0 (ng/ml) respectively. The concentrations of
      etoposide in aqueous and vitreous humors after infused in subconjunctival for 1,
      2, 3 hours were 98.0, 113.0, 99.0 (ng/ml) and 43.7, 66.7, 32.4 (ng/ml)
      respectively. The concentrations in the aqueous and vitreous humor after local
      administrated were 2 to 4 times higher than those obtained after intravenous
      administration. There are statistical significance between the concentrations of
      etoposide of aqueous and vitreous humor after intravenous and subconjunctival
      administration. CONCLUSIONS: The delivery of subconjunctival of etoposide results
      in higher concentrations in aqueous and vitreous humors than intravenous
      administration. These results suggest that local administration of
      chemotherapeutic agents should be more effective for retinoblastoma chemotherapy
      than systemic administration.

PMID- 15499730
TI  - Matrix metalloproteinases expression in choroidal neovascular membranes.
AB  - PURPOSE: To investigate the expression of matrix metalloproteinases (MMPs) in
      choroidal neovascular membranes with age-related macular degeneration (AMD).
      METHODS: Seventeen choroidal neovascular membranes surgically removed from AMD
      patients with pars plana vitrectomy and subretinal membranes peeling were
      investigated. The expression of MMP-2 and MMP-9 was determined with
      immunohistochemical technique. RESULTS: Immunohistochemistry staining in
      choroidal neovascular membranes for MMP-2 and MMP-9 was observed in 17 specimens.
      There was no detective of MMP-2 and MMP-9 in normal retinas. CONCLUSIONS: MMP-2
      and MMP-9 were found in choroidal neovascular membranes, may degrade the Bruch
      membrane and be associated with the perforation of new vessels into Bruch
      membrane, involving a basic pathogenic process of AMD.

PMID- 15499729
TI  - Adenovirally delivered brain-derived neurotrophic factor to rat retina.
AB  - PURPOSE: To study the expression of brain-derived neurotrophic factor (BDNF) in
      the rat retina delivered by adenovirus. METHODS: Adenovirus with BDNF gene was
      injected into the vitreous. Gene expression was detected by immunofluorescence
      staining,and quantitative analysis was performed after injury and transfection by
      Enzyme-linked immunosorbent assay (ELISA). RESULTS: The positive cells can be
      seen on the 3rd day and last 4 weeks by immunofluorescence staining. Positive
      cells in the control group were fewer than those in the transfection group or the
      fluorescence intensity was lower at every time point. Quantitative analysis
      showed that the expression of BDNF groups was higher than that of the control
      group at every time point (P < 0.01), and that of the injured group without
      transfection was higher than that of the control group on the 3rd day and the 7th
      day (P < 0.01). CONCLUSION: Efficient and stable transfer of BDNF gene could be
      achieved by adenovirus delivery into the retina of rats. Injury can promote the
      expression of BDNF in early period.

PMID- 15499731
TI  - Comparison of diode and argon laser lesions in rabbit retina.
AB  - PURPOSE: To compare the histological alteration of retina with various spot
      intensities between diode and argon lasers in order to instruct the clinical use
      of 810 nm diode laser. METHODS: Transpupillary retinal photocoagulations were
      performed on 42 eyes of 27 pigmented rabbits. Histopathologic alteration of
      lesions in different intensities and different time intervals after irradiation
      produced by diode and argon laser was observed and compared using light
      microscopy. Areas of various lesions measured by image analysis system (CMIAS)
      were compared quantitatively. RESULTS: Histopathologically, two-week-old grade 2
      lesions produced by diode laser induced the disappearance of outer nuclear cells.
      More than a half of all showed reduction in number of outer nuclear layer cells
      in argon. Fibroblasts appeared in the diode grade 3 lesions 5 days after
      irradiation. CMIAS data showed that all the areas of diode lesions immediately
      after photocoagulation were to be larger than those of argon laser lesions in the
      same spot intensity (P < 0.05). However, twenty-four hours after
      photocoagulation, the area of the diode lesions increased less than that of the
      argon laser lesions (8% vs. 23%). CONCLUSION: The acute histological effect
      caused by 810 nm diode laser and argon green laser is similar, while the
      expansion of lesion area 24 hours after photocoagulation was less with the diode
      laser compared to the argon. This may be the first report in the literature
      regarding quantitative analysis of the delayed reaction of argon green lasers.

PMID- 15499732
TI  - Perspectives. Doc-owned specialty hospitals have clinical pros and cons.

PMID- 15499733
TI  - Administration, legislators fight over 1.1 billion dollars in SCHIP money.

PMID- 15499734
TI  - Grassley, CMS: USP classes won't get formulary a free pass.

PMID- 15499735
TI  - Will higher-than-FFS payment solidify Medicare health plans?

PMID- 15499736
TI  - Unconventional wisdom.

PMID- 15499737
TI  - Election year yields flashes of bipartisan cooperation.

PMID- 15499738
TI  - Davila decision highlights importance of external review.

PMID- 15499739
TI  - The Davila decision: the politics of misunderstanding.

PMID- 15499740
TI  - Treasury makes HSAs an appealing alternative.

PMID- 15499741
TI  - The next medical breakthrough: defining a research agenda that helps improve
      health care quality.

PMID- 15499742
TI  - Creating the next generation of medical management.

PMID- 15499743
TI  - Engineering new strategies in specialty pharmacy management.

PMID- 15499744
TI  - Snapshots of success in the art of innovation.

PMID- 15499745
TI  - Complementary health care: no longer just an alternative.

PMID- 15499746
TI  - Insurance commissioners to the left, CMS to the right--here I am, stuck in the
      middle with you.

PMID- 15499747
TI  - Health plans increase efforts at giving teens a shot in the arm.

PMID- 15499748
TI  - Consumer-centered health care: the next generation of CDHC programs.

PMID- 15499749
TI  - Outsourcing and IT: keeping innovation in-house.

PMID- 15499751
TI  - The nosology of rosacea.
AB  - The National Rosacea Society (NRS) convened a committee of dermatology thought
      leaders to develop a standard classification system for rosacea. Based on the
      primary and secondary characteristics of this disorder, the NRS Expert Committee
      identified 4 types of rosacea: erythematotelangiectatic, papulopustular,
      phymatous, and ocular; one variant, granulomatous, also was recognized. The NRS
      Expert Committee also developed a grading system for rosacea signs and symptoms
      that will complement this classification system. The classification system and
      forthcoming grading system will help practitioners refine their diagnosis and
      treatment of rosacea to ensure better outcomes for patients.

PMID- 15499752
TI  - Rosacea and the pilosebaceous follicle.
AB  - The pathophysiology of rosacea remains unknown. A leading theory suggests a
      vascular basis; however, clinical observations and histopathologic studies
      suggest that inflammation of the pilosebaceous follicle may be central to the
      pathogenesis of rosacea. Demodex folliculorum is a frequently seen commensal in
      the follicles of facial skin. According to evidence from biopsies of the skin
      surface, individuals with rosacea have a higher density of this parasite. This
      increased mite density may play a role in the pathophysiology of rosacea by
      triggering inflammatory or specific immune reactions, mechanically blocking the
      follicles, or acting as a vector for bacteria. Ongoing research has shown that
      bacteria from patients with rosacea may behave differently at the higher skin
      temperature that may be present in patients with rosacea. Another group has
      isolated bacteria from the Demodex mites; these bacteria may play a pathogenic
      role in papulopustular rosacea by facilitating follicular-based inflammatory
      changes.

PMID- 15499753
TI  - Ultraviolet light and rosacea.
AB  - The general consensus among clinicians is that rosacea is a photoaggravated
      disorder. Pathophysiologic processes induced by UV radiation, which are processes
      similar to those seen in photoaging, contribute to the signs and symptoms of
      rosacea. Because of the purported role of solar radiation, clinicians may want to
      use photosensitizing antibiotics with discretion in patients with rosacea. In
      addition to topical and oral therapy for rosacea, clinicians should recommend
      that patients use sunscreens or sunblocks (inorganic chemicals such as zinc oxide
      or titanium dioxide).

PMID- 15499754
TI  - Reactive oxygen species and rosacea.
AB  - Although the fundamental pathogenesis of rosacea remains unknown, inflammation is
      a central process in this disorder. Recent evidence suggests that this
      inflammation is associated with the generation of reactive oxygen species (ROS)
      that are released by inflammatory cells such as neutrophils. In vitro studies
      suggest that certain core therapies for rosacea, including metronidazole and the
      tetracyclines, show antioxidant effects, and this may be one aspect of their
      mechanism of action.

PMID- 15499755
TI  - Rosacea subtypes: a treatment algorithm.
AB  - Based on various signs and symptoms, the National Rosacea Society (NRS) Expert
      Committee has divided the syndrome of rosacea into 4 major subtypes:
      erythematotelangiectatic, papulopustular (inflammatory), phymatous, and ocular.
      Each of the subtypes can be divided further into more specific subgroups. For
      example, sensory rosacea is an additional subtype that can be recognized and
      treated. Signs and symptoms may direct therapy. This article proposes an overview
      of common treatments based on subtypes. Treatments that have been validated by
      randomized controlled trials are reviewed. However, many excellent treatments
      have not been validated by double-blind randomized trials.

PMID- 15499756
TI  - Treating beyond the histology of rosacea.
AB  - Current treatment paradigms for rosacea focus on inflammatory lesions and other
      signs and symptoms of rosacea that appear on the skin surface. However, it is
      important to recognize the effects of the disease and its various treatments not
      only on the stratum corneum barrier but also on the biofilm. The effects of skin
      care products, cosmetics, and medications on the stratum corneum and biofilm must
      be carefully assessed, and nonirritating formulations should be used whenever
      possible.

PMID- 15499757
TI  - Barriers to biologics.

PMID- 15499758
TI  - Cryptococcal cellulitis in a patient on prednisone monotherapy for myasthenia
      gravis.
AB  - The development of cutaneous cryptococcosis is extremely rare in the human
      immunodeficiency virus-negative population. The cutaneous manifestations vary
      greatly, with the rarest presenting as cellulitis. We report a unique case of a
      64-year-old woman who had been on prednisone monotherapy for the treatment of
      myasthenia gravis and subsequently developed cryptococcal cellulitis. This case
      provides an opportunity to discuss the importance of including cryptococcal
      cellulitis in the differential diagnosis of cellulitis in a patient on low-dose
      prednisone who is not responding to empiric antibiotic therapy. Early recognition
      is crucial as cutaneous manifestations are usually the first sign of disseminated
      cryptococcosis.

PMID- 15499759
TI  - Keratosis punctata palmoplantaris controlled with topical retinoids: a case
      report and review of the literature.
AB  - Keratosis punctata palmoplantaris (KPPP) is a rare genodermatosis with an
      autosomal-dominant pattern of inheritance. We report the case of a 61-year-old
      woman who presented with a long history of multiple symptomatic hyperkeratotic
      papules on the palms and soles. In addition, we review the literature and present
      the current classification of the heterogeneous group of punctate palmoplantar
      keratoses, the cutaneous and histologic findings, the differential diagnosis, the
      possible association with various anomalies including malignancies, and the
      various treatment options.

PMID- 15499760
TI  - Sequential therapy using cyclosporine and acitretin for treatment of total body
      psoriasis.
AB  - Systemic sequential therapy using cyclosporine and acitretin is a novel strategy
      that can provide quick resolution and maintenance in refractory cases of
      psoriasis. We describe the case of a patient with a psoriatic flare over 98% of
      his body, despite methotrexate therapy. Implementing sequential therapy with
      cyclosporine and acitretin maximized the benefit of each treatment and allowed
      for rapid improvement with minimal risk of toxicity.

PMID- 15499761
TI  - The pathophysiology of acne vulgaris in children and adolescents, part 2:
      Tailoring treatment.
AB  - Various pathophysiologic factors are involved in the development of acne lesions,
      microcomedones, comedones, and inflammatory lesions. These factors include
      follicular hyperkeratosis, increased colonization of follicles by
      Propionibacterium acnes, increased sebum production, and inflammatory mediators.
      Optimal treatment of acne involves the use of agents that address these various
      underlying pathogenetic factors.

PMID- 15499762
TI  - Clinical benefits in patients with psoriasis after efalizumab therapy: clinical
      trials versus practice.
AB  - Evaluations of efficacy of the new biologic therapies for psoriasis have used
      both physician-assessed endpoints and patient-reported outcome measures. The
      Psoriasis Area and Severity Index (PASI) is commonly used in clinical trials but
      is too labor intensive for clinical practice, which uses more subjective measures
      (physician global assessment [PGA] of change and Overall Lesion Severity [OLS]
      scale). Because psoriasis affects quality of life (QOL), patient-reported
      assessments of their satisfaction with treatment also are important. The purpose
      of this study was to evaluate some of the measurement tools used in clinical
      trials to make them more applicable to the practicing dermatologist. We used
      results of a placebo-controlled clinical study of efalizumab for the treatment of
      patients with moderate to severe plaque psoriasis. After treatment, ratings of
      improvement in psoriasis as measured by the PASI and PGA were closely aligned. It
      was noted the latter tool could provide a more practical and user-friendly
      evaluation in clinical practice. After 12 weekly subcutaneous injections of
      efalizumab, patients who achieved > or = 50% but < 75% improvement in PASI had
      treatment responses rated as primarily good or excellent using the PGA;
      additionally, the patients treated with efalizumab had statistically significant
      improvements (P<.001) in all patient-reported QOL assessments compared with
      placebo-treated patients, as did patients who achieved a > or = 75% improvement
      in PASI (PASI 75).

PMID- 15499763
TI  - Clobetasol propionate lotion in the treatment of moderate to severe plaque-type
      psoriasis.
AB  - Owing to its anti-inflammatory, antipruritic, vasoconstrictive, and immune
      modulating properties, clobetasol propionate is used to treat psoriasis. This
      study was conducted to evaluate the efficacy, safety, and cosmetic acceptability
      of clobetasol propionate lotion compared with its vehicle and with clobetasol
      propionate cream in the treatment of moderate to severe plaque-type psoriasis. A
      total of 222 patients were treated. After 4 weeks of treatment, clobetasol
      propionate lotion was more efficient than vehicle lotion and of equivalent
      efficacy as clobetasol propionate cream. Cosmetic acceptability was significantly
      better with clobetasol propionate lotion than with clobetasol propionate cream.
      Clobetasol propionate lotion was efficient, safe, and well tolerated and offers a
      significantly higher cosmetic advantage in the treatment of moderate to severe
      plaque-type psoriasis compared with clobetasol propionate cream.

PMID- 15499764
TI  - Soil quality: a review of the science and experiences in the USA.
AB  - An increasing human population is placing greater demand on soil resources, and
      as a result degradation is taking place in many regions of the world. This is
      critical because soils perform a number of essential processes including
      supporting food and fiber production, influencing air quality through interaction
      with the atmosphere, and serving as a medium for storage and purification of
      water. The soil quality concept was introduced to complement soil science
      research by making our understanding of soils more complete and helping guide the
      use and allocation of labor, energy, fiscal, and other inputs as agriculture
      intensifies and expands to meet increasing world demands. Soil quality thus
      provides a unifying concept for educating professionals, producers, and the
      public about the important processes that soils perform. It also provides an
      assessment tool for evaluating current management practices and comparing
      alternative management practices. Soil attributes comprising a minimum data set
      have been identified, and both laboratory and field methods have been developed
      for measuring them. A soil quality index is being developed to normalize measured
      soil quality indicator data and generate a numeric value that can be used to
      compare various management practices or to assess management-induced changes over
      time. Using previously published data, we evaluated the soil quality index as a
      tool to assess a wide range of management practices in the Northern Great Plains.
      The index ranked the treatments: grazed fertilized tame pasture > moderately
      grazed > ungrazed > heavily grazed > annual cropping with no-tillage >
      conventionally tilled crop-fallow which agrees with the way they were
      subjectively ranked in the publications. The soil quality index shows potential
      for use as a management assessment tool.

PMID- 15499765
TI  - Soil quality evolution after land use change from paddy soil to vegetable land.
AB  - A survey was done in 15 typical villages, 150 soil and 86 vegetable plant samples
      were taken in Jiaxin prefecture of the Taihu Lake region, northern Zhejian
      province. Results indicate that after 15-20 years land use changed from the paddy
      rice-wheat (or oilseed rape) double cropping system, to a continuous vegetable
      land has caused soil quality dramatic change. (1) Acidification: average soil pH
      was 5.4; about 61% of total samples were pH < 5.5. It was 0.9 units lower than 10
      years ago with same upland vegetable cultivation and was 1.2 units lower than
      soil pH of paddy rice-wheat (or oilseed rape) rotation. (2) Fertilizer salt
      accumulation: the average salt content was 0.28%, among these about 36.2% of the
      total samples contained more than 0.3%. (3) Nitrate N and available phosphorus
      (P) over accumulation: on average it was 279 mg NO3-N/kg, and 45-115 mg P/kg.
      Nitrate N four times higher and available P 4-10 times more than it is in present
      paddy rice-wheat rotation soils respectively. This has caused wide concern
      because of possible groundwater and well drinking water pollution by leached
      nitrate N and the P losses to water by runoff from vegetable lands induce surface
      water eutrophication.

PMID- 15499766
TI  - Chemical changes in agricultural soils of Korea: data review and suggested
      countermeasures.
AB  - The monitoring of chemical properties, including heavy metals, in soils is
      necessary if better management and remediation practices are to be established
      for polluted soils. The National Institute of Agricultural Science and Technology
      initiated a monitoring study that investigated fertility and heavy metal contents
      of the benchmarked soils. The study covered paddy soils, upland soils, and
      horticultural soils in the plastic film houses, and orchard soils throughout the
      Korea from 1990 to 1998. Likewise, 4047 samples of paddy and 2534 samples of
      plastic house in 1999 and 2000 were analyzed through the Soil Environment
      Conservation Act. Soil chemical properties such as pH, organic matter, available
      phosphate and extractable calcium, magnesium and potassium contents, and heavy
      metal contents such as cadmium, copper, lead, zinc, arsenic, mercury, and cobalt
      contents were analyzed. The study showed that the average contents of organic
      matter, available phosphate, and extractable potassium rapidly increased in
      plastic house soils than in upland or paddy soils. Two kinds of fertilizer
      recommendation systems were established for the study: the standard levels by
      national soil average data for 77 crops and the recommendation by soil test for
      70 crops. Standard nitrogen fertilizer application levels for cereal crops
      changed from 94 kg/ha in 1960s, 99 kg/ha in 1970s, 110 kg/ha in 1980s to 90 kg/ha
      in 1990s. The K2O-fertilizer also changed from 67 kg/ha in 1960s, 76 kg/ha in
      1970s, 92 kg/ha in 1980s, and only 44 kg/ha in 1990s. In rice paddy fields, the
      average contents of Cd, Cu, Pb, and Zn in surface soils (0-15 cm depth) were 0.11
      mg kg(-1) (ranged from 0 to 1.01), 4.70 mg kg(-1) (0-41.59), 4.84 mg kg(-1) (0
      66.44), and 4.47 mg kg(-1) (0-96.70), respectively. In the uplands, the average
      contents of Cd, Cu, Pb, Zn, and As in surface soils (0-15 cm depth) were 0.135 mg
      kg(-1) (ranged from 0 to 0.660), 2.77 mg kg(-1) (0.07-78.24), 3.47 mg kg(-1) (0
      43.00), 10.70 mg kg(-1) (0.30-65.10), and 0.57 mg kg(-1) (0.21-2.90),
      respectively. In plastic film houses, the average contents of Cd, Cu, Pb, Zn, and
      As in surface soil were 0.12 mg kg(-1) (ranging from 0 to 1.28), 4.82 mg kg(-1)
      (0-46.50), 2.68 mg kg(-1) (0-46.50), 31.19 mg kg(-1) (0.19-252.0), and 0.36 mg
      kg(-1) (0-4.98), respectively. In orchard fields, the average contents of Cd, Cu,
      Pb, Zn, As, and Hg in surface soils (0-20 cm depth) were 0.11 mg kg(-1) (ranged
      from 0-0.49), 3.62 mg kg(-1) (0.03-45.30), 2.30 mg kg(-1) (0-27.80), 16.60 mg kg(
      1) (0.33-105.50), 0.44 mg kg(-1) (0-4.14), and 0.05 mg kg(-1) (0.01-0.54),
      respectively. For polluted soils with over the warning content levels of heavy
      metals, fine red earth application, land reconsolidation and soil amelioration
      such as lime, phosphate, organic manure, and submerging were recommended. For the
      countermeasure areas, cultivation of non-edible crops such as garden trees,
      flowers, and fiber crops; land reformation; and heavy application of fine red
      earth (up to 30 cm) were strongly recommended. Land use techniques should be
      changed to be harmonious with the environment to increase yield and income. Soil
      function characteristics should be taken into account.

PMID- 15499767
TI  - Changes of soil microbiological properties caused by land use changing from rice
      wheat rotation to vegetable cultivation.
AB  - A survey was done recently in Jiaxing city of Zhejiang Province in the Yangtze
      River Delta to compare the differences of soil microbiological properties among
      paddy soils with different land use including continuous open-field vegetable
      cultivation (OFVC), plastic-greenhouse vegetable cultivation (PGVC) and
      traditional rice-wheat rotation (RWR). The soil types included are percolating,
      permeable and waterlogged paddy soils. The results indicate that the microbial
      flora was markedly changed as the land use changed for all the three soil types.
      In continuous vegetable cultivation soils, especially in PGVC soils, the bacteria
      amounts decreased dramatically, but the fungal and actinomyce amounts increased
      as compared with RWR soils. The dehydrogenase activities decreased significantly
      in vegetable soils, especially in PGVC soils as compared with RWR soils. The
      microbial biomass C and the total phospholipid contents (TPL) in vegetable
      cultivation soil greatly decreased as compared with RWR soils. Biolog analysis
      indicated that the kinds of carbon sources that could be metabolized by native
      microbes in PGVC soils greatly decreased as compared with OFVC soils and RWR
      soils, revealing that microbial diversity had decreased since land use change.
      The activities of some soil enzymes including urease, invertase and phosphase
      were all lower in OFVC soils than those in RWR soils, and those in PGVC soils
      were the lowest. The degradation of microbiological activities in continuous
      vegetable cultivation soils, especially in PGVC soils, as compared with RWR soils
      might have been caused by soil acidification and accumulation of salts due to
      overuse of both organic and inorganic fertilizers in vegetable cultivation.

PMID- 15499768
TI  - Use of flyash as environmental and agronomic amendments.
AB  - Coal combustion power plant flyash materials have been reported as useful soil
      amendments with agronomic and environmental benefits. This paper reports the
      efficacy of fluidized bed combustion (FBC) and flue gas desulfurization (FGD)
      byproducts, when amended with dairy, swine, and broiler litter manures, in
      reducing phosphorus (P) solubility and potential impact on water quality. At a
      rate of 400 g/kg, FBC reduced water soluble P by 60% for dairy and swine and 50%
      for broiler litter, as compared to un-treated control samples. Byproduct FGD had
      little effect when amended into dairy manure, but reduced water soluble P by
      nearly 80% when amended into swine and broiler manure at a rate of 250 g/kg. The
      amount of Ca added in the amendments together with pH of the mixture is the major
      contributing factor in soluble P reduction. Sequential extraction results showed
      that the flyash treatments shifted water soluble P into mainly bicarbonate
      extractable P. The latter is still considered available for crop uptake but less
      vulnerable for environmental losses. Coal combustion byproducts, when amended
      into manure and used properly, can provide a useful and viable option for
      improving nutrient management on animal farms.

PMID- 15499769
TI  - Environmental assessment of water, sediment and plants in the Mankyeong River,
      ROK.
AB  - This study was carried out to evaluate water quality, sediment and plant
      vegetation in eight tributaries of the Mankyeong River for enhancement of natural
      purification. Among the tributaries, the Iksancheon water had the highest
      concentration of BOD, T-N and NH4-N due to inflow of swine wastes from the
      livestock district. The Yucheon water had the highest level of electrical
      conductivity and SO4(2-) due to inflow of mis-treated wastewater from industrial
      districts. The Tabcheon had generally similar concentrations of nitrogen and
      phosphate to that of the upstream of the Mankyeong River: agricultural activity
      along the Tabcheon appeared to have little negative influence to the water
      quality. Among various sediments, concentration of organic matter, nitrogen and
      phosphate were high in the Iksancheon and the Yucheon due to the livestock wastes
      and industrial wastes. There were 282 species of plants during summer with 43
      aquatic plants, 57 hydrophytes, 178 waterside plants and 4 terrestrial plants.
      Some plant resources were recommended due to much absorption of nitrogen and
      phosphate for enhancement of natural purification. C. demersum and H.
      verticillata were recommended in the submerged aquatic plants, H. dubia, N.
      indica and N. subinteperrimum in the floating leaf aquatic plants, P. communis,
      Z. latifolia and T. orientalis in the emerged aquatic plants, C. scutata and P.
      distichum in the waterside plants.

PMID- 15499770
TI  - Quantification and index of non-point source pollution in Taihu Lake region with
      GIS.
AB  - The contribution of phosphorus and nitrogen from non-point source pollution (NPS)
      in the Taihu Lake region was investigated through case study and surveying in the
      town of Xueyan, From experimental results coupled with survey and statistics in
      the studied area, the distribution of nitrogen and phosphorus input to the water
      body is achieved from four main sources: agricultural land, village, the town
      center and the poultry factory. The results showed that about 38% of total
      phosphorus (TP) and 48% of total nitrogen (TN) discharged is from agricultural
      land, 33% of TP and 40% TN from village residents, 25% of TP and 10% of TN from
      the town center and 4% of TP and 2% of TN from the poultry factory. The
      Agricultural Non-point Pollution Potential Index (APPI) system for identifying
      and ranking critical areas of NPS was established with a Geographic Information
      Systems (GIS)-based technology. Quantification of the key factors in non-point
      sources pollution was carried out utilizing the following: Sediment Production
      Index (SPI), Runoff Index (RI), People and Animal Loading Index (PALI) and
      Chemical Use Index (CUI). These are the core parts of the model, and the
      weighting factor of each index was evaluated according the results of
      quantification. The model was successfully applied for evaluating APPI in Xueyan.
      Results from the model showed that the critical area identified for NPS control
      in Xueyan. The model has several advantages including: requiring fewer
      parameters, easy acquirement of these parameters, friendly interface, and
      convenience of operation. In addition it is especially useful for identifying
      critical areas of NPS when the basic data are not fully accessible, which is the
      present situation in China.

PMID- 15499771
TI  - Assessment of contamination by percolation of septic tank effluent through
      natural and amended soils.
AB  - Fly ash has been found to be a potential material for the treatment of municipal
      and industrial wastewater, and may be useful in the treatment of septic tank
      effluent. Laboratory columns (30 cm) were used to determine the sorption capacity
      and hydraulic properties of lagoon fly ash, loamy sand, sand, and sand amended by
      lagoon fly ash (30 and 60%) and red mud gypsum (20%). The removal of chemical
      oxygen demand (COD) was high in all column effluents (71-93%). Extent of
      nitrification was high in Spearwood sand, Merribrook loamy sand and 20% red mud
      gypsum amended Spearwood sand. However, actual removal of nitrogen (N) was high
      in columns containing lagoon fly ash. Unamended Spearwood sand possessed only
      minimal capacity for P sorption. Merribrook loamy sand and red mud gypsum amended
      sand affected complete P removal throughout the study period of 12 weeks.
      Significant P leakage occurred from lagoon fly ash amended sand columns following
      6-10 weeks of operation. Neither lagoon fly ash nor red mud gypsum caused any
      studied heavy metal contamination including manganese (Mn), lead (Pb), zinc (Zn),
      cadmium (Cd) and chromium (Cr) of effluent. It can be concluded that Merribrook
      loamy sand is better natural soil than Spearwood sand as a filter medium. The
      addition of lagoon fly ash enhanced the removal of P in Spearwood sand but the
      efficiency was lower than with red mud gypsum amendment.

PMID- 15499772
TI  - Atmospheric sulfur deposition onto different ecosystems over China.
AB  - The regional acid deposition model system (RegADMS) was applied to simulate the
      air sulfur deposition onto different landuse types over China, in which the dry
      deposition velocities of SO2 and sulfate aerosol (SO4(2-) were estimated by use
      of a big leaf resistance analogy model and the wet scavenging coefficients were
      parameterized in terms of precipitation rate. Investigations show that the annual
      total sulfur deposition over mainland China is 7.24mt (1 mt = 10(6) ton) , in
      which dry deposition and wet deposition accounts for 56 and 44%, respectively.
      The sulfur deposition onto agriculture land, grass land, and forest land is 1.09,
      3.6 and 1.41 mt, respectively, which sums 6.1 mt and accounts for 84% of the
      total sulfur deposition. The modeled sulfur deposition was in agreement with the
      measurement conducted at farmland in Yingtan, a typical read soil region in
      Jiangxi province of China, during the period of November 1998--October 1999. The
      total sulfur deposition at the Yingtan site is about 10.3 gm(-2) year(-1) of
      which 83% is dry deposition. The modeling sulfur deposition at the same site is
      8.4 g m(-2) year(-1) Furthermore, the comparison between RegADMS and RAINS-ASIA
      on modeling regional sulfur deposition shows the consistence of the two models.
      The correlation coefficient between the simulated sulfur deposition at the medium
      large cities reaches 0.72.

PMID- 15499773
TI  - Atmospheric deposition, mineralization and leaching of nitrogen in subtropical
      forested catchments, South China.
AB  - In recent years, China has conducted considerable research focusing on the
      emission and effects of sulphur (S) on human health and ecosystems. By contrast,
      there has been little emphasis on anthropogenic nitrogen (N) so far, even though
      studies conducted abroad indicate that long-range atmospheric transport of N and
      ecological effects (e.g. acidification of soil and water) may be significant. The
      Sino-Norwegian project IMPACTS, launched in 1999, has established monitoring
      sites at five forest ecosystems in the southern part of PR China to collect
      comprehensive data on air quality, acidification status and ecological effects.
      Here we present initial results about N dynamics at two of the IMPACTS sites
      located near Chongqing and Changsha, including estimation of atmospheric
      deposition fluxes of NOx and NHx and soil N transformations. Nitrogen deposition
      is high at both sites when compared with values from Europe and North America (25
      38 kg ha(-1) yr(-1)). About 70% of the deposited N comes as NH4, probably derived
      from agriculture. Leaching of N from soils is high and nearly all as NO3-.
      Transformation of N to NO3- in soils results in acidification rates that are high
      compared to rates found elsewhere. Despite considerable leaching of NO3- from the
      root zone of the soils, little NO3- appears in streamwater. This indicates that N
      retention or denitrification, both causing acid neutralization, may be important
      and probably occur in the groundwater and groundwater discharge zones. The soil
      flux density of mineral N, which is the sum of N deposition and N mineralization,
      and which is dominated by the N mineralization flux, may be a good indicator for
      leaching of NO3- in soils. However, this indicator seems site specific probably
      due to differences in land-use history and current N requirement.

PMID- 15499774
TI  - A study on the spatial distribution of nitrogen and phosphorus balance, and
      regional nitrogen flow through crop production.
AB  - The spatial distribution patterns of the nitrogen and phosphorus input/intake
      amounts in crop production within two small basins are examined, based upon a
      cropping unit distribution map that is obtained from remote sensing data
      analysis. Firstly, we examine the availability and suitability of approaches to
      the spatial distribution analysis of cultivation patterns classified from
      material flow characteristics of crop production using seasonal remote-sensing
      data. Secondly, material flow units in crop production are grouped according to
      the cultivation patterns obtained from the remote-sensing data analysis.
      Consequently, the spatial patterns of the amounts of both nitrogen and phosphorus
      inputs/intakes through crop production on farmland are examined and their spatial
      distribution maps are prepared according to the material flow units. In addition,
      we developed a nitrogen flow and runoff model and the model is simulated based on
      the examination of the results of spatial distribution patterns of the material
      flow units. The annual nitrogen runoff from small catchments, where various crops
      are cultivated, varies from 2.7 kg ha(-1) year(-1) to 108 kg ha(-1) year(-1) and
      the annual balanced losses of nitrogen in small catchments varied from -30 kg ha(
      1) year(-1) to 101 kg ha(-1) year(-1). Also, the monthly changes in soil nitrogen
      of each material flow unit is estimated at -55 kg ha(-1) as a maximum decrease
      and 114 kg ha(-1) as a maximum increase. These results indicate that the spatial
      distribution patterns of nutrient input and intake through agricultural
      activities should be considered when analyzing the material flows and nutritient
      movement in soil-water systems in rural areas for watershed environmental control
      and regional agricultural management.

PMID- 15499775
TI  - Nitrogen export from an agriculture watershed in the Taihu Lake area, China.
AB  - Temporal changes in nitrogen concentrations and stream discharge, as well as
      sediment and nitrogen losses from erosion plots with different land uses, were
      studied in an agricultural watershed in the Taihu Lake area in eastern China. The
      highest overland runoff loads and nitrogen losses were measured under the upland
      at a convergent footslope. Much higher runoff, sediment and nitrogen losses were
      observed under upland cropping and vegetable fields than that under chestnut
      orchard and bamboo forest. Sediment associated nitrogen losses accounted for 8
      43.5% of total nitrogen export via overland runoff. N lost in dissolved inorganic
      nitrogen forms (NO(3-)-N + NH4+-N) accounted for less than 50% of total water
      associated nitrogen export. Agricultural practices and weather-driven fluctuation
      in discharge were main reasons for the temporal variations in nutrient losses via
      stream discharge. Significant correlation between the total nitrogen
      concentration and stream discharge load was observed. Simple regression models
      could give satisfactory results for prediction of the total nitrogen
      concentrations in stream water and can be used for better quantifying nitrogen
      losses from arable land. Nitrogen losses from the studied watershed via stream
      discharge during rice season in the year 2002 were estimated to be 10.5 kg N/ha
      using these simple models.

PMID- 15499776
TI  - Case study on nitrogen and phosphorus emissions from paddy field in Taihu region.
AB  - The agricultural non-point source pollution by nitrogen (N) and phosphorus (P)
      loss from typical paddy soil (whitish soil, Bai Tu in Chinese) in the Taihu Lake
      region was investigated through a case study. Results shown that the net load of
      nutrients from white soil is 34.1 kg ha(-1) for total nitrogen (TN), distributed
      as 19.4 kg ha(-1), in the rice season and 14.7 kg ha(-1) in the wheat season, and
      for total phosphorus (TP) 1.75 kg ha(-1), distributed as 1.16 kg ha(-1) in the
      rice season and 0.58 kg ha(-1) in the wheat season. The major chemical species of
      N loss is different in the two seasons. NH4-N is main the form in the rice season
      (53% of TN). NO3-N is the main form in wheat season (46% of TN). Particle-P is
      the main form in both seasons, (about 56% of TP). The nutrient loss varied with
      time of the year. The main loss of nutrients happened in the 10 days after
      planting, 64% of TN and 42% of TP loss, respectively. Rainfall and fertilizer
      application are the key factors which influence nitrogen and phosphorus loss from
      arable land, especially rainfall events shortly after fertilizer application. So
      it is very important to improve the field management of the nutrients and water
      during the early days of planting.

PMID- 15499777
TI  - Optimum nitrogen use and reduced nitrogen loss for production of rice and wheat
      in the Yangtse Delta region.
AB  - A long-term field and lysimeter experiment under different amount of fertilizer-N
      application was conducted to explore the optimal N application rates for a high
      productive rice-wheat system and less N leaching loss in the Yangtse Delta
      region. In this region excessive applications of N fertilizer for the rice-wheat
      production has resulted in reduced N recovery rates and environment pollution.
      Initial results of the field experiments showed that the optimal N application
      rate increased with the yield. On the two major paddy soils (Hydromorphic paddy
      soil and Gleyed paddy soil) of the region, the optimal N application rate was 225
      270 kg N hm(-2) for rice and 180-225 kg N hm(-2) for wheat, separately. This has
      resulted in the highest number of effective ears and Spikelets per unit area, and
      hence high yield. Nitrogen leaching in the form of NO(3-)-N occurs mainly in the
      wheat-growing season and in the ponding and seedling periods of the paddy field.
      Its concentration in the leachate increased with the N application rate in the
      lysimeter experiment. When the application rate reached 225 kg N hm(-2), the
      concentration rose to 5.4-21.3 mgN l(-1) in the leachate during the wheat-growing
      season. About 60% of the leachate samples determined contained NO(3-)-N beyond
      the criterion (NO(3-)-N 10 mg l(-1)) for N pollution. In the field experiment,
      when the N application rate was in the range of 270-315 kg hm(-2), the NO(3-)-N
      concentration in the leachate during the wheat-growing season ranged from 1.9 to
      11.0 mg l(-1). About 20% of the leachate samples reached close to, and 10%
      exceeded, the criterion for N pollution. Long-term accumulation of NO(3-)-N from
      leaching will no doubt constitute a potential risk of N contamination of the
      groundwater in the Yangtse Delta Region.

PMID- 15499778
TI  - Phosphorus losses to water from lowland rice fields under rice-wheat double
      cropping system in the Tai Lake region.
AB  - To assess P losses to surface water by runoff during the rice season and by
      drainage flow during the winter wheat season, serial field trials were conducted
      in different types of paddy soils in the Tai Lake Region (TLR) during 2000 and
      2001. Four P application rates were set as 0 (CK), 30, 150, and 300 kg P/hm2 for
      flooded rice trials and 0 (CK), 20, 80, 160 kg P/hm2 for winter wheat trials
      respectively. Field experiments were done in two locations with a plot size of 30
      m2 and four replications in a randomized complete block design. A simplified
      lysimeter was installed for each plot to collect all the runoff or drainage flow
      from each event. Total P (TP) losses to surface water during rice season by
      runoff flow from four treatments were 150 (CK), 220 (T30), 395 (T150), 670 (T300)
      g P/ hm2 in year 2000, and 298, 440, 1828, 3744 g P/hm2 in year 2001 respectively
      in Wuxi station, here the soil is permeable paddy soil derived from loam clay
      deposit. While the losses were 102, 140, 210, 270 in year 2000, and 128, 165,
      359, 589 g P/hm2 in year 2001 respectively in Changshu station, here the soil is
      waterlogged paddy soil derived from silt loam deposit. During the winter wheat
      season, total P lost from the fields by drainage flow in the four treatments were
      253 (CK), 382 (T20), 580 (T89), 818 (T160) g P/hm2 in year 2000--2001, and 573.3,
      709.4, 1123.2, 1552.4 g P/hm2 in year 2001--2002 at the Wuxi station. While these
      were 395.6, 539.1, 1356.8, 1972.1 g P/hm2 in year 2000--2001, and 811.5, 1184.6,
      3001.2, 5333.1 g P/hm2 in year 2001--2002 at the Changshu station. Results
      revealed that P fertilizer application rates significantly affected the TP
      concentrations and TP loads in runoff during the rice season, and by drainage
      flow during the winter wheat season. Both TP loads were significantly increased
      as the P application rate increases. The data indicate that TP losses to surface
      water were much higher during the winter wheat season than during the rice season
      in two tested sites. The data also reveal that the annual precipitation and
      evaporation rate affected the soil P losses to surface water significantly. Year
      2000 was relatively dried with higher evaporation thus P losses to water by both
      runoff and drainage flow were less than in year 2001 which was a relatively wet
      year with lower evaporation. Results indicate that texture, structure of the soil
      profile, and field construction (with or without ridge and deep drains) affected
      soil P losses to surface water dramatically. Annual possible TP lost to water at
      the application rate of 50 kg P/hm2 year tested in TLR were estimated from 97 to
      185 tones P from permeable paddy soils and 109-218 tones P from waterlogged paddy
      soils. There was no significant difference of TP lost between the CK and the T50
      treatments in both stations, which indicate that there is no more TP lost in
      field of normal P fertilizer application rate than in control field of no P
      fertilized. Much higher TP lost in runoff or drainage flow from those other P
      application rates treatments than from the T50 treatment, which suggest that P
      losses to surface water would be greatly increasing in the time when higher
      available P accumulation in plough layer soil in this region.

PMID- 15499779
TI  - Field studies on 32P movement and P leaching from flooded paddy soils in the
      region of Taihu Lake, China.
AB  - Field experiments were done in two sites, Yixing and Changshu, Jiangsu province,
      China, to study P movement and leaching in flooded paddy soils. P movement in
      soil was investigated by using the KH2 32PO4 tracker method, and the amount of P
      leached from the soil layer in different depths was estimated by measuring P
      concentrations in the soil solution and saturated hydraulic conductivities in
      field. Determination was done about one month after P application. There was 46%
      and 42% of total 32P retained in the 0-5cm layer of soil in the Yixing site and
      in the Changshu site respectively. The 32P retained in the 25-30 cm layer was
      only about 1-2% of the total 32P added. Furthermore, 8.01% of 32P in the soil of
      Yixing site and 16.8% of 32P in the soil of Changshu site was lost from the layer
      0-30 cm soil. The seasonal amounts of P leached from the top soil layer and from
      bottom layer are about 4.5-5.8% and 1.6-2.1% of the total P application,
      respectively. Changes of total P concentrations in soil solutions during rice
      growth showed that the fertilizer P applied before flooding of the paddy fields
      suffered a flash leaching loss and a slow leaching loss. We concluded that the
      fertilizer P could quickly move in the flooded paddy rice field and parts of it
      can enter into surface water and ground water. Unless the P application is well
      managed the risk of P loss and consequently environmental pollution exist.

PMID- 15499780
TI  - Nitrogen and phosphorus cycling in shrimp ponds and the measures for sustainable
      management.
AB  - Six ponds of age 3 were selected 45 km north from Suzhou in the Tailake region,
      and research conducted on nitrogen and phosphorus cycling in P. vannanmei
      (Penaeus vannanme) ponds and M. nipponense (Macrobrachium nipponense) hatchery
      ponds under normal management. Two treatments each had three replications. The
      results confirmed that feed was the major path of nitrogen and phosphorus input,
      each accounted for 61.24% (193.81 kg ha(-1)) and 81.08% (45.20 kg ha(-1)) of the
      total nitrogen and phosphorus input for P. vannanme ponds; the values for M.
      nipponense ponds were 43.93% (86.31 kg ha(-1)) and 57.67% (14.61 kg ha(-1)),
      respectively. Water pumped into ponds contributed on average 83.57 kg ha(-1)
      nitrogen and 8.48 kg ha(-1) phosphorus for P. vannanmei ponds, and 87.48 kg ha(
      1) nitrogen and 7.00 kg ha(-1) phosphorus for M. nipponense hatchery ponds.
      Shrimp harvest recovered 102.81 kg ha(-1) nitrogen (32.94% of the total nitrogen
      input) and 7.94 kg ha(-1) phosphorus (14.23% of the total phosphorus input) for
      P. vannanme ponds; and 43.94 kg ha(-1) nitrogen and 4.46 kg ha(-1) phosphorus for
      M. nipponense hatchery ponds. The sum of nitrogen losses through volatilization,
      denitrification and sedimentation was 173.62 and 122.39 kg ha(-1), 54.86% and
      62.29% of the total nitrogen input for P. vannanme ponds and M. nipponense
      hatchery ponds, respectively. Sediment accumulated 41.46 and 14.63 kg ha(-1)
      phosphorus, 74.37% and 64.85% of the total phosphorus input for P. vannanm ponds
      and M. nipponense hatchery ponds. Draining and seeping caused 40.06 kg ha(-1)
      nitrogen (12.66% of total nitrogen input) and 6.36 kg ha(-1) phosphorus (11.40%
      of total phosphorus input) loss to the surrounding water from P. vannanme ponds
      in 114 days; 30.14 kg ha(-1) nitrogen (15.34% of the total input) and 4.45 kg ha(
      1) phosphorus (17.57% of the total input) to channel water from M. nipponense
      hatchery ponds in 87 days, respectively. Countermeasures for sustainable pond
      management include improving feeds and feeding, sediment treatments, machine
      aerating, chemicals with no pollution, and integrated fish-shrimp cultivation.
      Management of water resources for pond and methods to reduce nitrogen and
      phosphorus loading into surrounding water from drainage are elucidated.

PMID- 15499781
TI  - Distribution of organo-chlorine pesticides (DDT and HCH) between plant and soil
      system.
AB  - This paper reports a study of the distribution of organo-chlorine pesticides (DDT
      and HCH) between rice plants and the soil system by spraying before the heading
      stage at four different dosage levels--control, normal dosage (15 kg ha(-1) of 6%
      HCH and 7.5 kg ha(-1) of 25% DDT), double dosage and four times dosage. Soil and
      plant samples were taken respectively at the 1st h, 3rd, 10th, 20th, and 40th day
      after spraying and at the harvest time. The results indicate that less than 5% of
      HCH and 15% of DDT were absorbed by the surface of rice leaves for normal dosage.
      Most of both pesticides moved into the soil in solution after spraying. Compared
      with DDT, HCH was degraded and run off more easily. HCH residues in the surface
      soil layer (1-3 cm) were already below 6.4 microg kg(-1) at the mature stage,
      lower than Chinese Environmental Quality Standard for Agricultural Soils: HCH <
      0.05 mg kg(-1). However DDT residues in the surface soil layer remained 172
      microg kg(-1), higher than the national standard: DDT < 0.05 mg kg(-1). According
      to the test f OCP residues in rice seeds, it can be concluded that the OCP
      sprayed onto the surface of rice leaves can move into rice plants and accumulate
      in the seeds at the mature stage. HCH residues in rice seeds of the double and
      four times dosage treatments, and DDT residues in all treatments, exceeded the
      Chinese National Food Standard (HCH < 0.10 mg kg(-1), DDT < 0.20 mg kg(-1)).

PMID- 15499782
TI  - Residues of organochlorinated pesticides in eggs of water birds from Tai Lake in
      China.
AB  - The levels of organochlorine compounds in eggs of water birds from the colony on
      Tai Lake in China were studied. The eggs were collected in 2000 and belonged to
      the following species: 65 samples of black-crowned night heron (Nycticorax
      nycticorax), 36 samples of little egret (Egretta garzetta), 26 samples of cattle
      egret (Bubulcus ibis) from 13 clutches and 43 samples of Chinese pond heron
      (Ardeola bacchus) from 17 clutches. Dichlorodiphenyltrichloroethane (DDT) and its
      derivates (DDE and DDD), hexachlorocyclohexane (HCH) and its isomers (alpha-HCH,
      beta-HCH, gamma-HCH, delta-HCH), heptachlor, heptachlor epoxide, aldrin,
      dieldrin, endrin, endrin aldehyde, alpha-endosulfan, beta-endosulfan, and
      endosulfan sulfate were determined in the laboratory by gas chromatography. The
      data showed that DDE had the highest levels in all the samples, followed by beta
      HCH. The mean levels of DDE among the water bird species were in the order as
      follows: black-crowned night heron (5464.26 ng/g, dry weight) > Chinese pond
      heron (2791.12 ng/g, dry weight) > little egret (1979.97 ng/g, dry weight) >
      cattle egret (660.11 ng/g, dry weight). DDT and its metabolites accounted for 90%
      of the total organochlorines, except that it was only 73% for cattle egret. The
      differences of the residue among the bird species were statistically significant
      and could be attributed to their variations in prey and habitat. Although the DDE
      burdens in Tai Lake were much lower than 8 microg/g (wet weight) which are
      thought to have significant adverse effects on black-crowned night herons, they
      would be expected to increase the risk of adverse effects on survival of chicks
      of herons and egrets, particularly black-crowned night heron, based on the
      critical value of 1 microg/g (wet weight) DDE. The burdens of HCHs in this study
      were higher and the cyclodienes were lower than those found elsewhere.

PMID- 15499783
TI  - Loss of pesticides from agricultural fields in SE Norway--runoff through surface
      and drainage water.
AB  - Loss of two pesticides with different mobility characteristics, bentazone (Koc
      approximately 34) and propiconazole (Koc approximately 1800), were studied at
      three agricultural fields (Askim, Bjornebekk and Syverud) in SE Norway. A
      conservative tracer (Br) was used to follow the flow of water. The loss of
      pesticides varied among the fields, depending on hydrological characteristics and
      soil properties. The loss of pesticides was higher from two artificially levelled
      silty clay loam soils with poor aggregate stability (Askim and Bjornebekk)
      compared to a loam/silt loam soil with increased content of organic carbon and
      better aggregate stability (Syverud). The total accumulated loss was <0.5% from
      all fields. The highest pesticide concentrations were measured at the first
      runoff episode after application for both the mobile (bentazone) and less mobile
      pesticide (propiconazole) in the surface runoff. In the drainage water, the peak
      for the less mobile pesticide coincided with the Br tracer, while the peak for
      mobile pesticide appeared earlier than the Br tracer. Rapid movement of water,
      particles and pesticides through soils indicate flow through macropores. Larger
      proportions (in percent of total applied) of both the mobile and the strongly
      sorbed pesticides were lost through the drainage as compared to the loss through
      surface runoff at Askim. Here, it is suggested that macropore flow contribute to
      the increased loss of pesticides through the drainage. At Syverud, high
      infiltration capacity reduces the amount of water available for surface runoff,
      and somewhat higher loss of the mobile pesticide was registered in the drainage
      compared to the surface runoff. For the strongly sorbed pesticide, however,
      propiconazole was neither detected in surface nor in drainage water at Syverud.
      Generally, there was a higher percentage loss of the mobile compared to the
      strongly sorbed pesticide in both surface and drainage water, which is in
      agreement with the pesticides mobility characteristics in soil. An exception was,
      however, the erodible soil Bjornebekk, where a higher fraction of propiconazole
      was lost in the surface runoff compared to bentazone. Large amounts of sediment
      transport from the Bjornebekk field probably contributed to enhanced transport of
      the strongly sorbed pesticide.

PMID- 15499784
TI  - Single and joint effects of acetochlor and urea on earthworm Esisenia foelide
      populations in phaiozem.
AB  - Much attention is paid to soil health and environmental safety. Earthworms are an
      important indicator of soil ecosystem health and safety. Ecological toxicity of
      acetochlor and excessive urea, in both their single and joint effects, on
      earthworm Esisenia foelide was thus studied using the soil-culture method.
      Acetochlor had an enhanced toxicity from low concentration to high concentration.
      The mortality of earthworms after a 6-day exposure was changed from 0 to 86.7%,
      and the weight change rate ranged from 7.86 to -30.43%, when the concentration of
      acetochlor was increased from 164 to 730 mg kg(-1). Urea expressed its positive
      and beneficial effects on earthworms when its concentration was lower than 500 mg
      kg(-1). Strongly toxic effects took place when the concentration of urea was
      higher than 1000 mg kg(-1). The mortality of earthworms exposed to urea reached
      100% when its concentration was more than 1500 mg kg(-1). When the concentration
      of urea was lower than 500 mg kg(-1), there were antagonistic effects between the
      two agrochemicals on earthworms; when the concentration of urea was higher than
      500 mg kg(-1), joint toxic effects of acetochlor and excessive urea on earthworms
      were synergic. In any case, excessive urea application is very harmful to the
      health of soil ecosystems.

PMID- 15499785
TI  - Degradation of benzo[a]pyrene in soil with arbuscular mycorrhizal alfalfa.
AB  - Mycorrhizal and non-mycorrhizal alfalfa (Medicago sativa) was grown in pots
      containing soil artificially contaminated with various levels of benzo[a]pyrene
      (B[a]P) (0, 1, 10 and 100 mg kg(-1)). Soil and plants were sampled after 30, 40,
      50, 60 and 90 days and compared with unlanted pots. The percentage of mycorrhizal
      root length colonized by Glomus caledoniun was not significantly affected by the
      addition of B[a]P up to 10 mg kg(-1) but was significantly lower at 100 mg kg(
      1)B[a]P compared with low concentrations (p < 0.05). There was no difference in
      soil polyphenol oxidase and dehydrogenase activity among the controls and
      applications of 1 and 10 mg kg(-1) of B[a]P. However, enzyme activities were
      significantly higher at 100 mg kg(-1) B[a]P compared with the other three
      treatments, and there was no mycorrhizal effect. Over a period of 90 days the
      concentration of B[a]P in soil in which alfalfa was grown was significantly lower
      than in unplanted soil (p < 0.05). Degradation rates of B[a]P added at 1, 10 and
      100 mg kg(-1) without G. caledonium were 76, 78 and 53%, and with mycorrhizal
      inoculation were 86, 87 and 57%. The degradation rate in unplanted soil was
      significantly lower than in planted soil, and was significantly higher in medium-
      and low-B[a]P treatments than in the high B[a]P concentration tested. There is a
      possibility of enhancement phytoremediation of PAHs in rhizosphere soil with
      arbuscular mycorrhizal fungi.

PMID- 15499786
TI  - Influences of suspended particles on the runoff of pesticides from an
      agricultural field at Askim, SE-Norway.
AB  - Field and laboratory experiments were conducted to study the loss of particles
      from agricultural fields, and the role of suspended particles in carrying
      pesticides in surface runoff and drainage water. Propiconazole, a widely used
      fungicide was applied to experimental fields located at Askim, SE-Norway. Samples
      from surface runoff and drainage water were collected and analyzed for sediment
      mass, pesticides, particulate and dissolved organic carbon through a whole year.
      The surface soil and the runoff material were characterized by its particle size
      distribution, organic carbon content in size fractions and its ability to bind
      propiconazole. The results show that (1) particle runoff mostly occurred during
      the rainfall event shortly after harrowing in autumn. The highest particle
      concentration observed in the surface runoff water was 4600 mg l(-1), and in the
      drainage water 1130 mg l(-1); (2) the erosion of surface soil is size selective.
      The runoff sediment contained finer particle/aggregates rich in organic matter
      compared to its original surface soil; (3) the distribution coefficient (Kd) of
      propiconazole was significantly higher in the runoff sediment than in the parent
      soil. According to our calculation, particle-bound propiconazole can represent up
      to 23% of the total amount of propiconazole in a water sample with a sediment
      concentration of 7600 mg l(-1), which will significantly influence the transport
      behavior of the pesticide.

PMID- 15499787
TI  - Fractionation of heavy metals in surface sediments of Taihu Lake, East China.
AB  - The BCR (European Communities Bureau of Reference) three-step sequential
      extraction procedure was applied to fractionate heavy metals in the sediment of
      Taihu Lake. For the determination of total metal concentration of the sediments,
      sample digestion was achieved by using HF/H2O2/HNO3 (2/1/1) acid mixture in a
      microwave-irradiated closed vessel system. The concentrations of Cd, Ni, Cr, Zn,
      Cu and Pb in various extracts solutions were analyzed by Inductively Coupled
      Plasma Atomic Emission Spectrometry (ICP-AES). The results obtained from the BCR
      three-step sequential extraction indicated relatively high mobility of Zn, Cu, Pb
      and Ni in the sediments while Cd and Cr were poorly mobile. Enrichment of heavy
      metals was found in the sediments collected in the northern parts of Taihu Lake.
      In the sediments collected in the southern and western sides of the Lake, heavy
      metal concentrations were relatively low. The relationship between total organic
      carbon (TOC) and heavy metals concentrations in the sediments is discussed.

PMID- 15499788
TI  - The adsorption of lead and copper from aqueous solution on modified peat-resin
      particles.
AB  - Raw peat was modified with sulfuric acid, then mixed modified with resin to
      prepare the modified peat-resin particles. Using the batch experimental systems,
      the removal of heavy metals (copper and lead) on the modified peat-resin
      particles was investigated. The data of the adsorption isotherm could be fitted
      by the Langmuir equation well. The adsorption rate of heavy metals on modified
      peat-resin particles was very swift. The removal processes of heavy metals on
      modified peat-resin particles could be well described by pseudo-second order
      model. The adsorption rate of lead was affected by the initial heavy metal
      concentration, initial pH, particle size, agitation speed and particle mass. In
      the adsorption of heavy metals (lead and copper) on the modified peat-resin
      particles, ion exchange was the major reaction mechanism. Desorption data showed
      that the lead adsorbed by modified peat-resin particle could be desorbed by 0.5 N
      or 1.0 N HNO3. The desorption rate was swift. The experiments indicated that the
      modified peat-resin particles have great potential for the removal of heavy
      metals from wastewater.

PMID- 15499789
TI  - Effects of cadmium on nutrient uptake and translocation by Indian Mustard.
AB  - Plants that hyperaccumulate metals are ideal subjects for studying the mechanisms
      of metal and mineral nutrient uptake in the plant kingdom. Indian Mustard
      (Brassica juncea) has been shown to accumulate moderate levels of Cd, Pb, Cr, Ni,
      Zn, and Cu. In this experiment, 10 levels of Cd concentration treatments were
      imposed by adding 10-190 mg Cd kg(-1) to the soils as cadmium nitrate [Cd(NO3)2].
      The effect of Cd on phosphorus (P), potassium (K), calcium (Ca), magnesium (Mg),
      and the micronutrients iron (Fe), manganese (Mn), copper (Cu), and zinc (Zn) in
      B. juncea was studied. Plant growth was affected negatively by Cd, root biomass
      decreased significantly at 170 mg Cd kg(-1) dry weight soils treatment. Cadmium
      accumulation both in shoots and roots increased with increasing soil Cd
      treatments. The highest concentration of Cd was up to 300 mg kg(-1) d.w. in the
      roots and 160 mg kg(-1) d.w. in the shoots. The nutrients mainly affected by Cd
      were P, K, Ca, Fe, and Zn in the roots, and P, K, Ca, and Cu in the shoots. K and
      P concentrations in roots increased significantly when Cd was added at 170 mg kg(
      1), and this was almost the same level at which root growth was inhibited. Zn
      concentrations in roots decreased significantly when added Cd concentration was
      increased from 50 to 110 mg kg(-1), then remained constant with Cd treatments
      from 110 to 190 mg kg(-1). However, Zn concentrations in the shoots seemed less
      affected by Cd. It is possible that Zn uptake was affected by the Cd but not the
      translocation of Zn within the plant. Ca and Mg accumulation in roots and shoots
      showed similar trends. This result indicates that Ca and Mg uptake is a non
      specific process.

PMID- 15499790
TI  - Effects of the interactions between selenium and phosphorus on the growth and
      selenium accumulation in rice (Oryza sativa).
AB  - The solution culture, paddy soil culture and the simulation experiments in the
      laboratory were conducted to clarify the interactions between selenium and
      phosphorus, and its effects on the growth and selenium accumulation in rice.
      Results revealed that a suitable supply of selenium could promote rice growth and
      excessive selenium could injure rice plant, causing lower biomass, especially in
      the roots. The supply of selenite could enhance the selenium contents of rice
      shoots and roots in solution culture and in soil culture. The selenium
      concentrations in roots were much higher than those in shoots supplied with the
      same rates of selenium and phosphorus. The interaction between selenium and
      phosphorus was evident. When the phosphorus supply increased to meet the needs of
      plant growth, phosphorus could promote absorption and accumulation of selenium in
      the shoots. If the phosphorus supply was excessive, phosphorus could inhibit the
      accumulation of selenium in the shoots at the lower selenite level (2 micromol l(
      1)), but could not at the higher selenite level (10 micromol l(-1)). With the
      supply of phosphate increased, the selenium concentrations in the roots decreased
      significantly at both selenite levels. The presence of phosphate could decrease
      Se sorption on the soil surface and increase the selenium concentration in the
      soil solution. The concentrations of selenium in shoots and roots supplied with
      0.08 g kg(-1) phosphorus were lower than those with no phosphorus supplied. With
      the increase of phosphorus added to 0.4 g kg(-1), the selenium concentration in
      shoots and roots increased. The effect of phosphorus on the concentration was
      statistically significant at all three selenium levels.

PMID- 15499791
TI  - Nutrients can enhance phytoremediation of copper-polluted soil by Indian mustard.
AB  - An orthogonally designed experiment was conducted to study the single and
      combined effects of N, P and K on phytoremediation of Cu-polluted soil by Indian
      mustard. Addition of fertilizer N and P significantly increased Indian mustard
      shoot yield. Two high treatments combined with N resulted in the highest yields,
      followed by low-P combined with N. In contrast, high P with no N gave no yield
      increase and K had no effect on yield of Indian mustard. Nitrogen and P increased
      the amount of chlorophyll in the leaves, indicating that the yield increases were
      due to enhanced photosynthesis. Nitrogen application had no effect on plant Cu
      concentrations but addition of P slightly decreased plant Cu concentrations,
      likely a dilution effect resulting from the increase in yield. Among the
      treatments, N and P applied at 100 and 200 mg kg(-1) respectively with no K
      application resulted in the highest Cu uptake. Thus, a combination of low N and
      high P produced a yield increase in Indian mustard that was more than adequate to
      compensate for a slight decrease in Cu concentration, resulting in the highest Cu
      removal from the contaminated soil.

PMID- 15499792
TI  - The gubernaculum in testicular descent and cryptorchidism.
AB  - The gubernaculum plays an essential role in the complex mechanism of testicular
      descent and inguinal hernia closure. Understanding this complex developmental
      process is gradually allowing us insight into how to regulate normal descent and
      also treat maldescended testes.

PMID- 15499793
TI  - The descent of testis and reason for failed descent.
AB  - Although an enormous number of theories have been proposed to explain the descent
      of testis, none has provided a satisfactory explanation that covers the whole
      spectrum. Recent evidence suggests a hitherto unrecognized mechanism. This novel
      explanation precisely defihes all of the factors proven to be involved in the
      process, and links the features associated with normal or failed descent. The
      gubernaculum gives rise to both smooth and striated muscles. The testis is
      descended through the processus vaginalis via the propulsive force generated by
      the muscles. Propulsion describes the risk of torsion. Failure in descent in
      associated with a diminution in smooth muscle content, and a decrease in
      sympathetic tonus that depends on androgens. Alterations in G-protein linked
      signaling due to differences in primary messengers resulting from changes in
      sympathetic and parasympathetic tonuses provide the basis for blunting of
      testosterone response to human chorionic gonadotropin (hCG) and the decrease in
      fertility, but also for the increase in the risk of malignancy.

PMID- 15499794
TI  - Obliteration of processus vaginalis: aberrations in the regulatory mechanism
      result in an inguinal hernia, hydrocele or undescended testis.
AB  - The testis is descended through the processus vaginalis via propulsive force
      generated by the muscles derived from the gubernaculum. After propelling the
      testis, the smooth muscle should undergo programmed cell death for obliteration
      of the processus vaginalis. Achievement of programmed cell death mandates a
      transient decrease in sympathetic, but an increase in parasympathetic, tonuses.
      Since the sympathetic tonus is androgen-dependent, the decrease in androgen
      levels during the third trimester appears to be responsible for the process.
      Alterations in timing, intensity or duration of the decrease in sympathetic tonus
      under the control of the central nervous system give rise to hernia, hydrocele or
      abnormal testis localizations. The persistence of decrease causes undescended,
      retracted, or ascended testis. Absence or inadequacy of the decrease in
      sympathetic tonus results in rescue of more smooth muscle, thus inhibiting the
      obliteration. Inadequacy in the intensity or duration rescues less smooth muscle
      and gives rise to a hydrocele. Persistence of signals towards inducing programmed
      cell death contributes to decrease in fertility, and provides a basis for
      epididymo-vasal anomalies. The reduction in the central regulatory mechanism that
      involves catecholaminergic activity explains the blunting of luteinizing hormone
      (LH) response to gonadotropin-releasing hormone (GnRH). The explained mechanism
      precisely defines the role of all factors, and links all of the associations
      related to the process of descent.

PMID- 15499795
TI  - Transgenic and knockout mouse models for aberrant pituitary-testicular function:
      relevance to the pathogenesis of cryptorchidism.
AB  - In recent years novel information about the hormonal regulation of testicular
      descent has emerged from genetically modified mice and other experimental animal
      models with cryptorchid phenotypes. We have studied transgenic (TG) mice
      overexpressing P450 aromatase (AROM+) and insulin-like 3 (INSL3+), and knockout
      (KO) mice for the genes of LH receptor (R) (LuRKO) and the thyroid-specific
      enhancer/binding protein T/ebp/Nkx2.1. LuRKO and AROM+ males are cryptorchid,
      while the INSL3 overexpressing females present with transabdominal descent of the
      ovaries. The T/ebp/Nkx2.1 KO mice die at birth, but the transabdominal phase of
      their testicular descent is normal despite the lack of pituitary gland. Detailed
      analysis of these mouse models brings novel information about the hormonal
      requirements, and their spatio-temporal aspects, in testicular descent, and how
      this process is affected by too low or too high hormone levels, or by imbalance
      in concentrations of critically important hormones.

PMID- 15499796
TI  - Testicular neoplasia in undescended testes of cryptorchid boys-does surgical
      strategy have an impact on the risk of invasive testicular neoplasia?
AB  - We investigated whether or not surgical strategy has an impact on the risk of
      invasive testicular neoplasia in cases of cryptorchidism. We made a database
      study of the incidence of testicular neoplasia at surgery for cryptorchidism in
      childhood, and evaluated if such abnormalities were found in special categories
      of patients, and also of the incidence of testicular neoplasia after orchiopexy
      with a simultaneous testicular biopsy in childhood. At surgery for cryptorchidism
      the risk of testicular neoplasia was 7/182 (4%) in cases with intra-abdominal
      testis, abnormal external genitalia other than cryptorchidism, or diagnosed
      abnormal karyotype, versus no case in the 1281 patients without these
      characteristics (Fisher's exact test, p < 0.00005). These clinical
      characteristics occurred most often in bilateral cryptorchidism 82/339 (24%)
      versus 103/1127 (9%) in unilateral cryptorchidism (Fisher's exact test, p <
      0.00005). At follow-up, the risk of testicular neoplasia was 7/830 (1%). The
      relative risk of testicular neoplasia was about 4. CONCLUSION: Based on our data
      and the literature we recommend: 1) Taking a testicular biopsy at surgery for
      cryptorchidism in childhood in intra-abdominally placed testes, or if the patient
      has abnormal external genitalia or a known abnormal karyotype. These clinical
      characteristics occur most often in cases of bilateral cryptorchidism. 2) Surgery
      for cryptorchidism before 10 years of age 3) Clinical control, after surgery for
      cryptorchidism. In cases of testicular atrophy orchiectomy must be considered.

PMID- 15499797
TI  - Ambulatory care visits to physician offices, hospital outpatient departments, and
      emergency departments: United States, 1999--2000.
AB  - OBJECTIVE: This report describes ambulatory care visits to physician offices,
      hospital outpatient departments (OPDs), and hospital emergency departments (EDs)
      as well as factors that may affect where care is sought. Ambulatory medical care
      utilization is described in terms of patient, practice/facility, and visit
      characteristics. Visits to office-based physicians are divided into the
      categories of primary care, surgical specialties, and medical specialties.
      METHODS: Data from the 1999 and 2000 National Ambulatory Medical Care Surveys
      (NAMCS) and National Hospital Ambulatory Medical Care Surveys (NHAMCS) were
      combined to produce averaged annual estimates of ambulatory medical care
      utilization. To examine changes over time, current data were compared with data
      from the 1993 and 1994 NAMCS and NHAMCS. RESULTS: Patients in the United States
      made an estimated 979 million visits per year in 1999 and 2000 to physician
      offices, hospital OPDs, and EDs, an annual rate of 3.6 visits per person. The
      distribution of visits by patient age, sex, race, expected source of payment,
      geographic region, and metropolitan statistical area (MSA) status varied across
      settings. The percentage of visits to office-based primary care physicians was
      similar for the characteristics studied, but the percentage of visits to office
      based surgical and medical specialists varied considerably. Black persons had
      higher visit rates than white persons to hospital OPDs and EDs but lower rates to
      office-based surgical and medical specialists. ED visits were more likely to be
      patient-paid or no charge than were visits to office-based physicians. Visit
      rates to office-based medical specialists decreased between 1993--94 and 1999-
      2000. Visit rates increased for hypertension and diabetes diagnoses, as did
      prescription rates for central nervous system, hormonal, pain relief, and
      respiratory tract drugs.

PMID- 15499798
TI  - Neurological assessment: a refresher.

PMID- 15499799
TI  - Your guide to choosing a travel company.

PMID- 15499800
TI  - Safety on assignment. A practical approach.

PMID- 15499801
TI  - Interview with Kevin Lofton, FACHE, president and chief executive officer,
      Catholic Health Initiatives, Denver, Colorado.

PMID- 15499802
TI  - Managing physician resistance to change.

PMID- 15499803
TI  - Five critical strategies for achieving operational efficiency.

PMID- 15499804
TI  - Community health orientation, community-based quality improvement, and health
      promotion services in hospitals.
AB  - The objective of the study presented in this article was to examine the
      relationship between hospital community orientation and the provision of health
      promotion services. The study used data from the 2000 American Hospital
      Association survey and the 2000 Area Resource File to examine acute care
      hospitals throughout the United States. The study was a cross-sectional multiple
      regression analysis. Hospital community orientation was measured by two
      independent variables: (1) community health orientation and (2) community-based
      quality orientation. Health promotion services were represented by two dependent
      variables: (1) hospital-based health promotion services and (2) collaborative
      health promotion services. Organizational control variables included bed-size
      code, not-for-profit ownership, network participation, and joint venture/alliance
      membership. Environmental control variables included the proportion of population
      over age 65, the percentage of population below the poverty level, the square
      root of the proportion of Medicaid inpatient revenue, the presence of state
      community benefit laws/guidelines, a Herfindahl-Hirschman Index of level of
      competition, and an index of managed care influence. Results of regression
      analyses showed that community health and community-based quality orientations
      were positively and significantly related to both the direct provision of health
      promotion services by hospitals and the collaborative provision of health
      promotion services through systems, joint ventures, and networks. The study
      concludes that a community health orientation and a community-based quality
      orientation lead to greater provision of health promotion services.

PMID- 15499805
TI  - Development and validation of a 360-degree-feedback instrument for healthcare
      administrators.
AB  - Multisource or 360-degree feedback has become a widely used component of
      leadership development in many organizations, and a growing body of research
      supports its use for this purpose. Unfortunately, most commercially available
      multisource surveys were developed in private-sector corporate settings, making
      their transferability to healthcare settings less than straightforward. This
      article describes a research project undertaken to develop a job-relevant,
      commercial-quality multisource feedback survey for use in health administration
      settings. Using critical incident methodology and enlisting the help of subject
      matter expert groups (i.e., executive search consultants, human resources
      executives, leadership development consultants, and administrative fellowship
      supervisors), a competency framework was developed containing 26 competencies
      arranged according to seven clusters. A third survey was then conducted with
      incumbent leaders to populate the competency framework with behavioral
      descriptors. The end result was a survey consisting of 128 total items that, when
      matrixed across four relationship types, create surveys ranging from 36 to 95
      items in length. Two pilot studies were then conducted to assess reliability as
      well as validity against other measures of leadership ability. Results from these
      studies suggest that the instrument can provide reliable and valid assessments of
      leadership effectiveness for development purposes.

PMID- 15499806
TI  - Improving resource efficiency through management science.
AB  - Optimal management of resources is a very complex and difficult task for
      healthcare systems. Nevertheless, healthcare providers can employ data-driven
      methodologies and management science tools, coupled with managerial insights, to
      significantly improve both their resource effectiveness and efficiency.
      Understanding the full technical complexities of management science models is a
      daunting task for healthcare managers, but they can be aided by the increased
      availability of management science software. Readily available software does not
      require extensive technical competencies and is easily adaptable to resource
      changes. This article reports how a large healthcare system improved the cost
      effectiveness and service efficiency of its laboratory courier service through
      the use of management science techniques and readily available software. The
      laboratory courier system existed to serve a large multihospital healthcare
      system located in a major Texas metropolis. The routing and scheduling solution
      reported in this article yielded a very substantial 16.4 percent reduction in
      annual laboratory courier costs and a significant improvement in service levels.
      This study indicates that management science techniques and software are readily
      adaptable to the healthcare environment and are amenable to use by healthcare
      administrators.

PMID- 15499807
TI  - Nursing home administrators' level of job satisfaction.
AB  - Job satisfaction has been shown to have a direct relationship to the quality of
      work. Are nursing home administrators satisfied with their work? How do they
      compare with their counterparts in other industries? The results of this survey,
      using the Job Description Index (JDI) and the Job in General (JIG) scale as
      published by Bowling Green State University, indicate that nursing home
      administrators have a more compressed rate of job satisfaction than their
      counterparts in other industries. They focus their dissatisfaction on their
      coworkers and pay. They demonstrate dissatisfaction by rotating their positions
      at a rate of every 31 months. This suggests some significant problems in the
      development and maintenance of quality care and some areas that could be
      addressed to raise the level of satisfaction among nursing home administrators.

PMID- 15499808
TI  - Passports cause concern at BEVA congress.

PMID- 15499809
TI  - Minimum inhibitory concentrations of some antimicrobial drugs against bacteria
      causing uterine infections in cattle.
AB  - The minimum inhibitory concentrations (MICs) of oxytetracycline, cephapirin,
      cephapirin/mecillinam, cefquinome, ceftiofur and enrofloxacin, candidate
      antibiotics for the principal bacteria associated with uterine infections:
      Escherichia coli, Arcanobacterium pyogenes and the anaerobic bacteria
      Fusobacterium necrophorum and Prevotella melaninogenicus, were determined by the
      agar dilution method. The bacteria were isolated from animals with clinical
      metritis and/or endometritis. For E coli, cefquinome and enrofloxacin had the
      lowest MIC90 and MIC50 values (< 0.06 microg/ml), and oxytetracycline and
      cephapirin had the highest values. For A pyogenes, oxytetracycline had the
      highest MIC50 value (16 microg/ml), but all the cephalosporins had values below
      0.06 microg/ml. For the anaerobic bacteria, enrofloxacin and oxytetracycline had
      the highest MIC50 values but all the cephalosporins had values of 0.06 microg/ml
      or below.

PMID- 15499810
TI  - Effects of vaccination against viral haemorrhagic disease and myxomatosis on long
      term mortality rates of European wild rabbits.
AB  - The effects of vaccination against myxomatosis and viral haemorrhagic disease
      (VHD) on long-term mortality rates in European rabbits (Oryctolagus cuniculus)
      were studied from 1993 to 1996 by radiotracking a free-living population of wild
      rabbits. During the three months after immunisation, unvaccinated young rabbits
      weighing between 180 and 600 g were 13.6 times more likely to die than vaccinated
      young rabbits. In adult rabbits, vaccination did not significantly decrease
      mortality, mainly owing to the high proportion of rabbits which had previously
      been exposed to the antigens of both diseases. Compared with adult rabbits with
      natural antibodies to VHD, rabbits without these antibodies were 5.2 times more
      likely to die of VHD during annual outbreaks.

PMID- 15499811
TI  - Computed tomographic measurements of the hip morphology of 10 healthy German
      shepherd dogs.
AB  - Linear measurements were made by computed tomography of the diameter of the
      femoral head, the width and depth of the acetabulum and the dorsal and ventral
      acetabular rim distances in 10 healthy German shepherd dogs, and angular
      measurements were made of the axial acetabular index, acetabular anteversion, and
      the dorsal and ventral centre-edge angles. There were no significant differences
      between the measurements made on the left and right sides. The width of the
      acetabulum was about twice its depth, and was a little larger than the diameter
      of the femoral head. The mean values of the axial acetabular index, acetabular
      anteversion, and ventral and dorsal centre-edge angles were 100.9 degrees, 25.1
      degrees, 48.0 degrees and 12.2 degrees, respectively.

PMID- 15499812
TI  - Antimicrobial resistance of Campylobacter jejuni and Campylobacter coli isolates
      in Japan.

PMID- 15499813
TI  - Attaching and effacing Escherichia coli O103:K+:H- in red-legged partridges.

PMID- 15499814
TI  - Seroepidemiological survey for Chlamydophila felis among household and feral cats
      in northern Italy.

PMID- 15499815
TI  - Persistent Mullerian duct syndrome causing male pseudohermaphroditism in a mixed
      breed dog.

PMID- 15499816
TI  - Danofloxacin treatment of cattle affected by CBPP.

PMID- 15499817
TI  - Vote on fox hunting.

PMID- 15499818
TI  - Granulomatous lesion in the brain of a four-month-old female calf.

PMID- 15499819
TI  - Perils of pet pigs.

PMID- 15499820
TI  - Reliability of sexually violent predator civil commitment criteria in Florida.
AB  - The present study investigated the reliability of Sexually Violent Predator (SVP)
      civil commitment criteria under Florida's Jimmy Ryce Act. The purpose of the
      study was to determine if, independently, 2 evaluators would reach the same
      conclusions about the same client (n = 295). According to civil commitment
      criteria outlined by the United States Supreme Court (Kansas v. Hendricks, 1997),
      SVPs must display a mental abnormality predisposing them to sexual violence and a
      likelihood of future sexual violence. The interrater reliability of 8 DSM-IV
      diagnoses applied by evaluators to determine whether a client has a "mental
      abnormality that predisposes him to sexual violence" was found to be poor to fair
      (kappa = .23 to . 70). The interrater reliability of risk assessment instruments
      used to determine "likelihood of reoffense" was good (ICC = .77 to .85). The
      recommendations made by evaluators regarding whether or not to refer a client for
      civil commitment demonstrated poor reliability (kappa = .54). Implications for
      practice and policy are explored.

PMID- 15499821
TI  - When does evidence of eyewitness confidence inflation affect judgments in a
      criminal trial?.
AB  - Two studies investigated perceptions of eyewitness confidence inflation:
      increases in a witness's confidence between the time of the identification and
      the trial. Experiment 1 (N = 90) demonstrated that, for White participants,
      assessments of the strength of the defense case, the eyewitness's view, and
      participants' confidence in the eyewitness's accuracy were more favorable to the
      defense when there was evidence that the eyewitness's confidence increased over
      time (mere inflation condition), compared with a control condition. In addition,
      assessments of the defendant's guilt and the eyewitness's accuracy were more
      favorable to the defense when the eyewitness was aggressively challenged about
      the change in her confidence report (inflation + challenge). Experiment 2 (N =
      360) demonstrated that, for Hispanic participants, sensitivity to confidence
      inflation did not interact with manipulations of the eyewitness's or defendant's
      race (White vs. Hispanic). In addition, the confidence inflation effect did not
      replicate with the Hispanic participants. Results are interpreted in terms of the
      ingroup bias in legal judgments and directions for future research.

PMID- 15499822
TI  - Firing back at the backfire effect: the influence of mortality salience and
      nullification beliefs on reactions to inadmissible evidence.
AB  - Two studies were conducted to explore psychological factors that contribute to
      the influence of inadmissible evidence (i.e., the backfire effect) on jurors'
      verdicts. On the basis of hypotheses derived from terror management theory, we
      predicted that reminders of mortality, in contrast to an aversive control topic,
      should lead participants to be less punitive when confronted with inadmissible
      (as opposed to admissible) evidence, when participants were either situationally
      induced or dispositionally prone to follow their personal sense of justice. In
      Study 1, control participants who scored high on a measure of nullification
      beliefs, and thus were prone to relying on their own sense of justice rather than
      the law, exhibited the backfire effect. However, reminding participants of their
      mortality reduced the damaging influence of inadmissible evidence. Study 2
      extended these findings by showing parallel effects with a manipulation of
      nullification proneness via judicial instructions. The implications of these
      factors on the judicial process are discussed.

PMID- 15499823
TI  - Children's lie-telling to conceal a parent's transgression: legal implications.
AB  - Children's lie-telling behavior to conceal the transgression of a parent was
      examined in 2 experiments. In Experiment 1 (N = 137), parents broke a puppet and
      told their children (3-11-year-olds) not to tell anyone. Children answered
      questions about the event. Children's moral understanding of truth- and lie
      telling was assessed by a second interviewer and the children then promised to
      tell the truth (simulating court competence examination procedures). Children
      were again questioned about what happened to the puppet. Regardless of whether
      the interview was conducted with their parent absent or present, most children
      told the truth about their parents' transgression. When the likelihood of the
      child being blamed for the transgression was reduced, significantly more children
      lied. There was a significant, yet limited, relation between children's lie
      telling behavior and their moral understanding of lie- or truth-telling. Further,
      after children were questioned about issues concerning truth- and lie-telling and
      asked to promise to tell the truth, significantly more children told the truth
      about their parents' transgression. Experiment 2 (N = 64) replicated these
      findings, with children who were questioned about lies and who then promised to
      tell the 'truth more likely to tell the truth in a second interview than children
      who did not participate in this procedure before questioning. Implications for
      the justice system are discussed.

PMID- 15499824
TI  - Assessing the risk of domestic violence reoffending: a validation study.
AB  - Little research has been conducted to validate available instruments for
      assessing the risk of domestic violence reoffending, especially research using
      some form of prospective design. This study uses a prospective design to
      determine the reliability and validity of the Domestic Violence Screening
      Instrument (DVSI). The analysis is based on a sample of 1,465 male domestic
      violence offenders selected consecutively over a 9-month period. Data on
      reoffending were collected in a 6-month follow-up period from a subsample of the
      victims (N = 125) of these perpetrators and from official records for all
      perpetrators during an 18-month follow-up period. The empirical results suggest
      that the DVSI was administered reliably, and they provide significant evidence of
      the concurrent, discriminant, and predictive validity of this instrument.
      Implications for further research and utilization of the DVSI are discussed.

PMID- 15499825
TI  - A review and critique of the Sexual Experiences Questionnaire (SEQ).
AB  - This paper reviews and critiques the Sexual Experiences Questionnaire (SEQ), "...
      a self-report inventory representing the first attempt to assess the prevalence
      of sexual harassment in a manner that met traditional psychometric standards"
      (Fitzgerald, Gelfand, & Drasgow, 1995, p. 427). Widely used by its developers and
      others as a measure of sexual harassment, the SEQ is not a finished product, has
      a number of problems, and has weak psychometric properties. Because of
      inconsistencies (e.g., in time frame, number of items, wording of items), the SEQ
      lacks the advantages of standardized measures, such as the ability to assess
      changes over time. It defines sexual harassment very broadly, having the effect
      of distorting findings about sexual harassment. Most importantly, it is not clear
      what or whose definition of sexual harassment the SEQ assesses.

PMID- 15499826
TI  - Thermal image scanners to detect fever in airline passengers, Vancouver and
      Toronto, 2003.

PMID- 15499827
TI  - Smallpox vaccination of laboratory workers.

PMID- 15499828
TI  - Ninth Oxford conference organised by the Oxford International Biomedical Centre
      (OIBC).

PMID- 15499829
TI  - Effects of the antiandrogen flutamide on the expression of protein kinase C
      isoenzymes in LNCaP and PC3 human prostate cancer cells.
AB  - Flutamide is a nonsteroidal antiandrogen that is frequently used for total
      androgen blockage in the treatment of advanced prostate cancer. We investigated
      the effect of this antiandrogen on the expression of protein kinase C (PKC)
      isoenzymes (alpha, beta1, epsilon, zeta) that are involved in cell growth,
      apoptosis and neoplastic transformation. Androgen-dependent (LNCaP) and
      independent (PC3) human prostate cancer cells were cultured in a medium that
      contained fetal bovine serum (FBS) or charcoal-stripped serum (CSS) and treated
      with 10 microM flutamide. The expression of PKC isoenzymes and the androgen
      receptor (AR) were analyzed by Western blot and RT-PCR, respectively. Serum
      steroids differentially regulate the expression of PKC isoenzymes in LNCaP and
      PC3 cells. Flutamide up-regulated the expression of alpha, beta1 and zeta, but
      not epsilon, PKC isoenzymes in CSS-LNCaP cells. These results were not
      homogeneously reproduced in the presence of androgens. We observed an opposite
      effect of flutamide, compared to CSS, on PKCbeta1 isoform expression in CSS-LNCaP
      suggesting that this antiandrogen exerts an agonistic effect. In PC3 cells
      flutamide potentiated the expression of the four PKC isoenzymes in almost all
      conditions tested (FBS- and CSS-cultured cells). Such effect of flutamide in PC3
      cells is independent of AR since no expression of AR was detected. These results
      provide new evidence on antagonistic/agonistic responses of prostate cancer cells
      to antiandrogen drugs that are widely used in therapy and show that flutamide can
      elicit responses in prostate cancer cells that do not express AR.

PMID- 15499830
TI  - Zinc lozenges: cold cure or candy? Solution chemistry determinations.
AB  - Common colds were shortened by 7 days in a 1984 clinical trial using zinc
      gluconate throat lozenges each 2 h. Between then and 2004, 10 other double-blind,
      placebo-controlled clinical trials showed widely varying results. This re
      analysis of these trials presents solution chemistry methods to elucidate
      differences in efficacy. Statistically significant correlation was shown between
      total daily dosages of positively charged zinc species and reductions in median
      (p = 0.005) and mean duration (p < 0.02) of common colds in these trials.

PMID- 15499831
TI  - NAD glycohydrolase activities and ADP-ribose uptake in erythrocytes from normal
      subjects and cancer patients.
AB  - Erythrocytes from cancer patients exhibited up to fivefold higher NAD
      glycohydrolase activities than control erythrocytes from normal subjects and also
      similarly increased [14C] ADP-ribose uptake values. When [adenosine-14C] NAD was
      used instead of free [14C] ADP-ribose, the uptake was dependent on ecto-NAD
      glycohydrolase activity. This was reflected in the inhibition of ADP-ribose
      uptake from [adenosine-14C] NAD by Cibacron Blue. ADP-ribose uptake in
      erythrocytes appeared to be complex: upon incubation with free [14C] ADP-ribose,
      the radiolabel associated with erythrocytes was located in nearly equal parts in
      cytoplasm and plasma membrane. Part of [14C] ADP-ribose binding to the membrane
      was covalent, as indicated by its resistance to trichloroacetic acid-treatment. A
      preincubation with unlabeled ADP-ribose depressed subsequent erythrocyte NAD
      glycohydrolase activity and binding of [14C] ADP-ribose to erythrocyte membrane;
      but it failed to inhibit the transfer of labeled ADP-ribose to erythrocyte
      cytoplasm. On the other hand, incubation with [adenosine-14C] NAD did not result
      in a similar covalent binding of radiolabel to erythrocyte membrane. In line with
      this finding, a preincubation with unlabeled NAD was not inhibitory on subsequent
      NAD glycohydrolase reaction and ADP-ribose binding. ADP-ribose binding and NAD
      glycohydrolase activities were found also in solubilized erythrocyte membrane
      proteins and, after size fractionation, mainly in a protein fraction of around
      45kDa-molecular weight.

PMID- 15499832
TI  - Modulation of antigenic phenotype by IL-1beta, IFNgamma and TGFbeta on cultured
      human decidual stromal cells.
AB  - Decidual stromal cells (DSC) constitute the most abundant population in normal
      human decidua together with leukocytes. Both populations may be involved in the
      immunological role of the decidua by favoring gestational functions,
      participating in physiological mechanisms to eliminate the fetus, or providing
      local defense against infection. Using flow cytometry, we investigated whether
      different cytokines modulate the expression on cultured DSC of antigen-presenting
      molecules. The treatment with IFNgamma or IL-1beta enhanced the expression of
      CD54. The percentage of expression of HLA-DR was enhanced by IL-1beta treatment
      but was not modified by IFNgamma. The expression of CD80 and CD86 was enhanced by
      IFNgamma treatment but was not modified by IL-1beta; the expression of CD86 and
      HLA-DR was reduced by TGFbeta1 treatment. The response of DSC and dendritic cells
      to these cytokines appears to be similar, suggesting a phenotypic and functional
      relationship between these cell types.

PMID- 15499833
TI  - Shifting shifts.

PMID- 15499834
TI  - Art of my craft.

PMID- 15499835
TI  - Opportunities abound: stay connected to healthcare initiatives.

PMID- 15499836
TI  - Help us chart a course for Canada's nursing professions.

PMID- 15499837
TI  - 2002 CNA Code of Ethics: some recommendations.
AB  - The Canadian Nurses Association (CNA) recently revised its 1997 Code of Ethics
      for Registered Nurses to reflect the context within which nurses practise today.
      Given the unprecedented changes that have taken place within the profession,
      healthcare and society, it was timely for the CNA to review and revise its Code.
      But the revisions were relatively minor; important problematic, substantive
      aspects of the Code were essentially left untouched and persist in the updated
      2002 Code. In this paper, three of those aspects are examined and discussed: the
      2002 Code's (a) definition of health and well-being, (b) notion of respect and
      (c) conception of justice. Recommendations are made. It is hoped that these
      comments will encourage nurse leaders in Canada to initiate discussion of the
      Code now, in preparation for its next planned revision in 2007.

PMID- 15499838
TI  - Commentary: who will define the values?

PMID- 15499839
TI  - Shared decision-making in nursing education.
AB  - Shared decision-making is an effective management strategy that may have positive
      implications for nurse educators facing curricular and course delivery issues.
      Use of shared or participative decision-making recognizes that decisions made for
      the overall good of the organization should include those integrally involved,
      i.e., faculty, students and administration. Ultimately, effective student
      learning should be the outcome of decisions related to curricular and content
      delivery. In this anecdotal paper, the authors present shared decision-making
      (SDM) as a management strategy that may be effectively utilized in a range of
      situations in educational settings. An exemplar is presented regarding changes in
      course delivery methods at two sister schools of nursing. Strategies to promote
      successful implementation, as well as challenges in initiating SDM, are
      discussed. The information presented in this paper can benefit nurse educators by
      offering a collaborative approach to the issues of evolving nursing curricula and
      content delivery.

PMID- 15499840
TI  - Commentary: the road to success in nursing education.

PMID- 15499841
TI  - University Health Network framework for advanced nursing practice: development of
      a comprehensive conceptual framework describing the multidimensional
      contributions of advanced practice nurses.
AB  - BACKGROUND: The global paradigm shift resulting from radical transformations in
      knowledge and technology is significantly changing the context of healthcare
      delivery. In this changing environment, the contributions of health professions
      are vital in ensuring that the healthcare system adapts to meet the needs of
      today's patient. Advanced practice nurses (APNs) are clinical scholars and
      leaders in creating innovative approaches to patient care and organizational and
      professional leadership. AIMS: To develop a comprehensive conceptual framework
      for advanced nursing practice at University Health Network that will enhance role
      clarity by describing the complexity of these nursing roles and the significant
      contributions they make to patients and the healthcare system. METHODS: A
      critical review of the literature and a consultative process were undertaken to
      build consensus and develop a comprehensive framework for advanced nursing
      practice. RESULTS: The development of the University Health Network Framework for
      Advanced Nursing Practice (UHN-FANP), which clearly articulates all dimensions of
      advanced nursing practice roles. CONCLUSION: As clinical leadership roles in
      nursing continue to evolve, utilization of a conceptual framework facilitates
      role clarity, role implementation and role evaluation.

PMID- 15499842
TI  - Innovations in seniors' care: home care/physician partnership.
AB  - The Innovations in Seniors' Care (Primary Care Partnerships) Project was
      implemented in 2000 in the Calgary Health Region, Alberta, to look at integration
      of services for seniors. The goal was to develop a sustainable collaborative
      partnership between family physicians and Community Care Coordinators--RNs (Home
      Care). The design and model were established in Stage I of the project. Stage II
      addressed implementation, challenges, barriers, evaluation, learnings and
      successes to date. Stage III looked at refinement, revision, final evaluation of
      the processes and dissemination of learnings. This paper describes startup
      procedures and implementation (selection of participants, educational sessions,
      evolution of partnerships and development of the evaluation framework). As the
      focus of the project was quality improvement, the section on implementation will
      discuss how and why changes occurred in the course of the process. Key challenges
      related to the restructuring of Home Care, creating tools and fostering unique
      individualized partnerships are also discussed. The conclusion evaluates the
      project's benefits in relation to (1) participant satisfaction, (2)
      sustainability and (3) impact on the system. The initial partnerships were formed
      in May 2001. New partnerships continue to be developed and constitute a key
      strategy in the Calgary Health Region's Primary Care Initiative.

PMID- 15499843
TI  - Recruitment and retention of nurses: challenges facing hospital and community
      employers.
AB  - Understanding nurses' perceptions of their workplaces underpins successful
      recruitment and retention initiatives, particularly in this time of global
      nursing shortage. The American Nurses Association and the American Academy of
      Nursing have identified "magnet characteristics"--organizational factors that
      support excellent practice and working conditions in hospital settings. Using
      selected magnet characteristics, this exploratory study examined nurses'
      perceptions of their work experiences in both hospital and community settings.
      Mail surveys were completed by community and hospital nurses (n = 1248) selected
      randomly from a provincial registry in Ontario, Canada. Scales measured
      organizational factors (organizational and immediate supervisor support,
      decentralized decision-making, nurse-physician relationships and work-group
      cohesiveness) and job-related factors (autonomy, job challenge, work demands,
      fair treatment, work-status congruence; satisfaction with career, salary, working
      conditions) of nurses' experiences in their work settings. Nurses in both sectors
      wanted more opportunities to participate in decision-making and recognition for
      their contributions to their organizations. In the hospital sector, nurses
      reported significantly lower levels of perceived organizational and supervisory
      support and autonomy, and were less satisfied with working conditions and
      scheduling. Nurses in the community sector were most dissatisfied with salary. No
      cross-sector differences were reported on nurse-physician relationships, degree
      of job challenge or career satisfaction. Successful recruitment and retention
      initiatives hinge on the ability (and willingness) of healthcare organizations to
      attend to the concerns expressed by nurses and create work settings that are
      attractive to both new recruits and nurses currently in their employ.

PMID- 15499844
TI  - Photonic crystals--a step towards integrated circuits for photonics.
AB  - The field of photonic crystals has, over the past few years, received
      dramatically increased attention. Photonic crystals are artificially engineered
      structures that exhibit a periodic variation in one, two, or three dimensions of
      the dielectric constant, with a period of the order of the pertinent light
      wavelength. Such structures in three dimensions should exhibit properties similar
      to solid-state electronic crystals, such as bandgaps, in other words wavelength
      regions where light cannot propagate in any direction. By introducing defects
      into the periodic arrangement, the photonic crystals exhibit properties analogous
      to those of solid-state crystals. The basic feature of a photonic bandgap was
      indeed experimentally demonstrated in the beginning of the 1990s, and sparked a
      large interest in, and in many ways revitalized, photonics research. There are
      several reasons for this attention. One is that photonic crystals, in their own
      right, offer a proliferation of challenging research tasks, involving a multitude
      of disciplines, such as electromagnetic theory, nanofabrication, semi-conductor
      technology, materials science, biotechnology, to name a few. Another reason is
      given by the somewhat more down-to-earth expectations that photonics crystals
      will create unique opportunities for novel devices and applications, and
      contribute to solving some of the issues that have plagued photonics such as
      large physical sizes, comparatively low functionality, and high costs. Herein, we
      will treat some basics of photonic crystal structures and discuss the state-of
      the-art in fabrication as well give some examples of devices with unique
      properties, due to the use of photonic crystals. We will also point out some of
      the problems that still remain to be solved, and give a view on where photonic
      crystals currently stand.

PMID- 15499845
TI  - Ultrafast electron dynamics in metals.
AB  - During the last decade, significant progress has been achieved in the rapidly
      growing field of the dynamics of hot carriers in metals. Here we present an
      overview of the recent achievements in the theoretical understanding of electron
      dynamics in metals, and focus on the theoretical description of the inelastic
      lifetime of excited hot electrons. We outline theoretical formulations of the hot
      electron lifetime that originates in the inelastic scattering of the excited
      quasiparticle with occupied states below the Fermi level of the solid. First
      principles many-body calculations are reviewed. Related work and future
      directions are also addressed.

PMID- 15499846
TI  - Molecular origins of the remarkable chiral sensitivity of second-order nonlinear
      optics.
AB  - Recent observations of remarkably large chiroptical effects in second-harmonic
      generation (SHG) and sum-frequency generation (SFG) measurements suggest exciting
      possibilities for the development of new chiral-specific spectroscopies and novel
      chiral materials for nonlinear optics. Several fundamental studies designed to
      elucidate the molecular and macromolecular origins of the chiral responses are
      reviewed to provide a framework for development of this emerging field. In
      general, the chiral activity in SHG and SFG has the potential to arise from
      complex interactions between hosts of different competing effects. Fortunately,
      relatively simple electric dipole-allowed mechanisms routinely dominate the
      nonlinear optical chiral activities of most practical systemsexpressions can
      often be generated to link the. This substantial reduction in complexity allows
      for the development of simple models connecting the macroscopic nonlinear optical
      response to intuitive molecular and supramolecular properties.

PMID- 15499847
TI  - Optical spectroscopy of biomolecular dynamics.

PMID- 15499848
TI  - Femtosecond pump-probe measurements of solvation by hydrogen-bonding
      interactions.
AB  - An additional ultrafast blue shift in the transient absorption spectra of
      hydrogen-bonding complexes of a strong photoacid, 8-hydroxypyrene 1,3,6
      trisdimethylsulfonamide (HPTA), over the solvation response of the uncomplexed
      HPTA and also over that of the methoxy derivative of the photoacid (MPTA) in the
      presence of the hydrogen-bonding base was observed on optical excitation of the
      photoacid. The additional 55 +/- 10 fs solvation response was found to be about
      35 % and 19% of the total C(t) of HPTA in dichloromethane (DCM) when it was
      hydrogen-bonded to dimethylsulfoxide (DMSO) and dioxane, respectively, and about
      29% of the total C(t) of HPTA in dichloroethane (DCE) when it was hydrogen-bonded
      to DMSO. We have assigned this additional dynamic spectral shift to a transient
      change in the hydrogen bond (O-H...O) that links HPTA to the complexing base,
      after the electronic excitation of the photoacid.

PMID- 15499849
TI  - The effect of Ge incorporation on the Bronsted acidity of ZSM-5.
AB  - The effect of the isomorphous substitution of some of the Si atoms in ZSM-5 by Ge
      atoms on the Bronsted acid strength has been investigated by i) DFT calculations
      on cluster models of the formula ((HO)3SiO)3-Al-O(H)-T-(OSi(OH)3)3, with T=Si or
      Ge, and ((HO)3SiO)3-Al-O(H)-Si-(OGe(OH)3)(OSi(OH)3)2, ii) a 31P NMR study of
      zeolite samples contacted with trimethyl phosphine oxide probe molecules and iii)
      a X-ray photoelectron spectroscopy (XPS) study of ZSM-5 and Ge-ZSM-5 samples. The
      calculations reveal that the effect of Ge incorporation on the framework acidity
      strongly depends on the degree of substitution and on the exact T-atom positions
      that are occupied by Ge. High Ge concentrations allow for enhanced stabilisation
      of the deprotonated Ge-ZSM-5 through structural relaxation, resulting in a
      slightly higher acidity as compared to ZSM-5. This structural relaxation is not
      achievable in Ge-ZSM-5 with a low Ge content, which therefore has a slightly
      lower acidity than ZSM-5. The NMR study indicates no difference between the
      Bronsted acidity of ZSM-5(47) and Ge(0.09)ZSM-5(36). Instead, evidence for the
      presence of a substantial amount of Ge-OH groups in the Ge-containing samples was
      obtained from the NMR results, which is consistent with earlier FTIR studies. The
      XPS results do not point to an effect of Ge on the framework acidity of ZSM
      5(47), instead, the results can be best interpreted by assuming the presence of
      additional Ge-OH and Si-OH groups near the surface of the Ge(0.08)ZSM-5(47)
      sample.

PMID- 15499850
TI  - Theoretical study of the reactions of CF3OCHF2 with the hydroxyl radical and the
      chlorine atom.
AB  - Theoretical investigations are carried out on the reaction mechanism of the
      reactions of CF3OCHF2 (HFOC-125) with the OH radials and Cl atoms, as well as the
      heats of formation of CF3OCHF2 and CF3OCF2. The electronic structure information
      on the potential energy surface for each reaction is obtained at the B3LYP/6
      311G(d,p) level, and energetic information is further refined by G3(MP2) theory.
      The direct dynamics calculation of the hydrogen abstraction reactions are also
      performed at the G3(MP2)//B3LYP/ 6-311G(d,p) level. The classical energy profile
      is corrected by interpolated single-point energies (ISPE) approach, incorporating
      the small-curvature tunnelling effect (SCT) calculated by the variational
      transition-state theory (VTST). The rate constants are in good agreement with the
      experimental data and are found to be k1 = 4.95 x 10(-30)T(5.40)exp(-347/T) and
      k2 = 1.86 x 10(-23)T(3.43)exp(-1579/T) cm3 molecule(-1)s(-1) over the temperature
      range 200-2000 K. The rate constants at 298 K for these two reactions are 3.38 x
      10(-16) and 2.80 x 10(-17) cm3 molecule(-1)s(-1), respectively. Using group
      balanced isodesmic reactions as working chemical reactions, the standard
      enthalpies of formation for CF3OCHF2 and CF3OCF2 are -312.3 +/- 1.0 and -257.3 +/
      1.0 kcalmol(-1), respectively, evaluated by G3(MP2) theory based on the B3LYP/6
      311G(d,p) geometries. The theoretical studies provide rate constants of the title
      reactions and the enthalpies of the species, which are important parameters in
      determining the atmospheric lifetime and the feasible pathways for the loss of
      HFOC-125.

PMID- 15499851
TI  - A computational investigation of HCN2+ isomeric structures: implications for the
      chemistry of Titan's atmosphere.
AB  - The structure and stability of various HCN2+ isomeric structures have been
      investigated at the complete active space SCF (CASSCF) and multireference
      configuration interaction [MR-Cl-SD(Q)] levels of theory with the 6-31G(d) and 6
      311G(d,p) basis sets. The investigated species include the singlet (S) and
      triplet (T) open-chain H-N-C-N+ ions 1S, 1S', and 1T, the open-chain H-C-N-N+
      ions 2S, 2S', and 2T, the HC-N2+ cyclic structures 3S and 3T, and the HN-CN+
      cyclic structures 4S and 4T. All these species have been identified as true
      energy minima on the CASSCF(8,7)/6-31G(d) potential energy surface, and their
      optimised geometries, refined at the CASSCF(8,8)/6-31G(d) level of theory, have
      been used to perform single point calculations at the [MR-Cl-SD(Q]/6-311G(d,p)
      computational level. The most stable structure was the H-N-C-N+ ion 1T, whose
      absolute enthalpy of formation at 298.15 K has been estimated as 333.9 +/- 2
      kcalmol(-1) using the Gaussian-3 (G3) procedure. The two species closest in
      energy to 1T are the triplet H-C-N-N+ ion 2T and the singlet diazirinyl cation
      3S, whose G3 enthalpies of formation at 298.15 K are 343.5 +/- 2 and 340.6 +/- 2
      kcalmol(-1), respectively. Finally, we have discussed the implications of our
      calculations for the detailed structure of the HCN2+ ions formed in the reaction
      between N3+ and HCN, experimentally observed by flowing after-glow-selected ion
      flow/drift tube mass spectrometry and possibly occurring in Titan's atmosphere.

PMID- 15499852
TI  - The Diels-Alder reaction of ethene and 1,3-butadiene: an extended multireference
      ab initio investigation.
AB  - The concerted and stepwise mechanisms of the Diels-Alder reaction between 1,3
      butadiene and ethene have been investigated using highly correlated
      multireference methods (MRAQCC) and extended basis sets. Full MRAQCC geometry
      optimizations have been performed in all cases. The best estimate for the energy
      barrier of the Diels-Alder reaction is 22 kcalmol(-1). Anti- and gauche-out
      minima for the biradical structures and corresponding fragmentation saddle points
      have been determined. The biradical anti fragmentation saddle point is located
      6.5 kcalmol(-1) above the concerted saddle point. The gauche-in structure does
      not correspond to a local minimum, but leads on geometry optimization directly to
      cyclohexene.

PMID- 15499853
TI  - Quantum dynamics study of the excited-state double-proton transfer in 2,2'
      bipyridyl-3,3'-diol.
AB  - Density functional theory and quantum dynamics simulations have been used to
      study the double-proton transfer reaction in 2,2'-bipyridyl-3,3'-diol in the
      first singlet excited electronic state. This process is experimentally known to
      be branched: It consists of a fast, concerted reaction mechanism (tau
      approximately 100 fs) and a stepwise reaction mechanism [with a fast initial step
      (tau approximately 100 fs) and a slower final step (tau approximately 10 ps)].
      Quantum dynamics simulations on a two-dimensional model reveal that the concerted
      reaction occurs despite the nonexistence of a concerted reaction path, but they
      fail to explain the relative slowness of the stepwise mechanism. A qualitative
      simulation using a three-dimensional model suggests that internal vibrational
      relaxation (IVR) might be the reason why the second stage of the stepwise
      mechanism is so slow.

PMID- 15499854
TI  - Mechanism and kinetics of the reaction of OH radicals with glyoxal and
      methylglyoxal: a quantum chemistry + CVT/SCT approach.
AB  - A theoretical study of the mechanism and kinetics of the OH hydrogen abstraction
      from glyoxal and methylglyoxal is presented. Optimum geometries, frequencies, and
      gradients have been computed at the BHandHLYP/6-311++G(d,p) level of theory for
      all the stationary points, as well as for 12 additional points along the minimum
      energy path (MEP). Energies were obtained by single-point calculations at the
      above geometries using CCSD(T)/ 6-311++G(d,p) to produce the potential energy
      surface. The rate coefficients were calculated for the temperature range 200-500
      K by using canonical variational theory (CVT) with small-curvature tunneling
      (SCT) corrections. Our analysis suggests a stepwise mechanism, which involves the
      formation of a reactant complex. The overall agreement between the calculated and
      experimental kinetic data is very good. This agreement supports the reliability
      of the Arrhenius parameters of the glyoxal + OH reaction that are proposed in
      this work for the first time. The Arrhenius expressions that best describe the
      studied reactions are k1 = (9.63 +/- 0.23) x l0(-13)exp[(517 +/- 7)/T] and k2 =
      (3.93 +/- 0.11) x 10(-13)exp[(1060 +/- 8)/T]cm3 molecule(-1)s(-1) for glyoxal and
      methylglyoxal, respectively.

PMID- 15499855
TI  - Coherent oscillation and ultrafast internal conversion of tetrafluoroethene after
      excitation at 197 nm.
AB  - C2F4 was excited by using a 150 fs pulse in its longest-wavelength band to the
      Rydberg (3 s) state and then probed by photoionization techniques at 810 nm. The
      molecule relaxes in two consecutive steps (time constants 29 and 118 fs),
      probably via the pipi* state, which is lowered in energy by stretching and
      twisting the C=C bond. A coherent oscillation (350 fs) was found, which we assign
      to an overtone of the twist vibration (47.6 cm(-1)) in this state. we also
      conclude that dissociation to singlet and some triplet CF2 only takes place in
      the hot ground state of C2F4, from where also the C2F4 triplet state is
      populated. The potentials and their conical intersections are discussed with
      respect to relaxation and dissociation, including also some new considerations of
      thermal processes.

PMID- 15499856
TI  - Local dense structural heterogeneities in liquid water from ambient to 300 MPa
      pressure: evidence for multiple liquid-liquid transitions.
AB  - Difference and double-difference near-infrared DO-D and HO-H stretching overtone
      (2nuOD and 2nuOH) spectroscopy and a rigorous (physically substantiated) band
      deconvolution technique were applied to reveal three different kinds of inherent
      (interstitial) structures of liquid water, which determine its high density
      (compared to ice lh under ambient conditions), its compressibility (under
      hydrostatic pressure, up to 300MPa), and its high fragility (manifested under
      temperature variation). Our data processing allowed the rigorous discrimination
      of up to six vibrational components. On the basis of an extensive comparative
      analysis combined with available structural data (X-ray and neutron scattering)
      and molecular dynamics (MD) simulations for liquid water, as well as with
      experimental and computed data for small non-tetrahedrally arranged water
      clusters, the major four components could be ascribed to: i) The basic lh icelike
      substructure; ii) the temperature-dependent remote interstitial "defects" due to
      tetrahedral displacements (primarily responsible for transport properties); iii)
      the interstitial "defects" most probably arranged in quasiplanar noncyclic
      tetramers (totally absent in the ice structure); and iv) the interstitial
      "defects" formed with increasing pressure, probably arranged in cubic water
      octamers and composed of two pairs of noncyclic and cyclic tetramer fragments.
      The latter structures include, essentially, bent hydrogen bonds stabilized by
      resonance effects.

PMID- 15499857
TI  - Fabrication, characterisation and voltammetric studies of gold amalgam
      nanoparticle modified electrodes.
AB  - The tabrication, characterisation, and electroanalytical application of gold and
      gold amalgam nanoparticles on glassy carbon electrodes is examined. Once the
      deposition parameters for gold nanoparticle electrodes were optimised, the
      analytical utility of the electrodes was examined in CrIII electroanalysis. It
      was found that gold nanoparticle modified (Au-NM) electrodes possess higher
      sensitivity than gold macroelectrodes. In addition, gold amalgam nanoparticle
      modified (AuHg-NM) electrodes were fabricated and characterised. The response of
      those electrodes was recorded in the presence of important environmental analytes
      (heavy metal cations). It was found AuHg-NM electrodes demonstrate a unique
      voltammetric behaviour and can be applied for electroanalysis when enhanced
      sensitivity is crucial.

PMID- 15499858
TI  - Structural phase transitions in heavy alkali metals under pressure.
AB  - We performed a theoretical study of the crystal structures of cesium and rubidium
      under high compressions. Our results confirm the recent high-pressure
      experimental observations of new complex crystal structures for the Cs III and Rb
      III phases. The calculated transition pressures agree extremely well with the
      measured data. Thus, it is now certain that the famous isostructural phase
      transition in cesium is actually a new crystallographic phase transition. A d
      orbital occupation number of about 0.52 is crucial for the occurrence of these
      complex structures.

PMID- 15499859
TI  - Surface chemistry and structure of purified, ozonized, multiwalled carbon
      nanotubes probed by NEXAFS and vibrational spectroscopies.
AB  - Understanding of oxidative processes such as solution-phase ozonolysis in
      multiwalled carbon nanotubes (MWNTs) is of fundamental importance in devising
      applications of these tubes as components in composite materials, as well as for
      development of cutting and filling protocols. We present here an evaluation of
      various spectroscopic tools to study the structure and composition of
      functionalized nanotubes. We demonstrate near-edge X-ray absorption fine
      structure (NEXAFS) spectroscopy as a particularly useful and effective technique
      for studying the surface chemistry of carbon nanotubes.

PMID- 15499860
TI  - Femtosecond time-resolved hydrogen-atom elimination from photoexcited pyrrole
      molecules.

PMID- 15499861
TI  - Photostability of isolated and paired nucleobases: N-H dissociation of adenine
      and hydrogen transfer in its base pairs examined by laser spectroscopy.

PMID- 15499862
TI  - Spontaneous change of physical state from hydrogels to crystalline precipitates
      during poly-pseudorotaxane formation.

PMID- 15499863
TI  - Near-infrared electroluminescence from HgTe nanocrystals.

PMID- 15499864
TI  - Theoretical design of substituted tetrathia-[7]-helicenes with large second-order
      nonlinear optical responses.

PMID- 15499865
TI  - Enhanced molecular multipole moments and solvent structure in supercritical
      carbon dioxide.

PMID- 15499866
TI  - Isolation and characterisation of two Sc3N@C80 isomers.

PMID- 15499867
TI  - The maternity and infancy revolution.

PMID- 15499868
TI  - It's the vision thing: mobilizing the Grace Abbots of the twenty-first century.

PMID- 15499869
TI  - Racial and ethnic disparities in the use of pregnancy-related health care among
      Medicaid pregnant women.
AB  - OBJECTIVE: To assess the extent to which racial and ethnic disparities exist in
      the use of prenatal services among Medicaid pregnant women. METHODS: Medicaid
      claims data for Florida, Georgia, New Jersey, and Texas, with linked birth
      certificate data for Georgia and Texas, were used to investigate the use of
      selected prenatal services, including the initiation and adequacy of prenatal
      care visits; prescriptions for multiple vitamins and iron supplements; and claims
      for complete blood cell counts, blood type and RH status, hepatitis B surface
      antigen, ultrasound, maternal serum alphafetoprotein, drug screening, and HIV
      tests. We computed raw and adjusted odds ratios of having the health service of
      interest during pregnancy for women in three minority groups: black non
      Hispanics, Hispanics, and Asian/Pacific Islanders. RESULTS: We found racial and
      ethnic disparities in the use of every health service investigated. Compared with
      white non-Hispanics, minority women were less likely to receive services that the
      woman initiates, discretionary services, and services potentially requiring
      specialized follow-up care, whereas they were more likely to receive screening
      tests for diseases related to high-risk behaviors. Disparities were generally
      larger, more consistent across states, and less likely to be explained by other
      factors among black non-Hispanics than among either Hispanics or Asian/Pacific
      Islanders. CONCLUSIONS: Even among women who are provided equal financial access
      to health care services, unexplained racial and ethnic disparities persist in the
      initiation and use of both routine and specialized prenatal care services.

PMID- 15499870
TI  - Reductions in stress and depressive symptoms in mothers of substance-exposed
      infants, participating in a psychosocial program.
AB  - OBJECTIVE: Depression profoundly impairs psychosocial functioning. Depression can
      have disruptive effects on a person's family, with significant impact on the
      psychosocial development of the children. Recent research suggests that a
      mother's depressive symptoms may increase parenting stress and that parenting
      stress may, in turn, increase depressive symptoms, with a possible negative cycle
      to this process. Little is known about how these two factors interact in drug
      involved mothers. This study examines how the NEW CONNECTIONS intervention (a
      parental education and support program for drug-involved parents) acts on
      parental stress and symptoms of depression. METHODS: The study site was the NEW
      CONNECTIONS Infant Intervention Program. The Beck Depression Inventory-II (BDI
      II) and the Parenting Stress Index (PSI) were administered to drug- and alcohol
      involved mothers (N = 120) at baseline and after the intervention (Week 12).
      RESULTS: Four of the seven PSI domains of parenting stress showed a significant
      reduction (Demandingness, Competence, Isolation, and Role Restriction). Changes
      in four domains were significantly correlated with reductions in depressive
      symptoms (Competence, Isolation, Attachment, and Role Restriction). There was a
      significant reduction in depressive symptoms as measured by the BDI-II.
      CONCLUSION: Reduction in some aspects of parenting stress is associated with
      reduction in depressive symptoms in mothers of substance-exposed infants who
      participated in the NEW CONNECTIONS psychosocial intervention targeting the
      parent-child relationship.

PMID- 15499871
TI  - Awareness and acceptance of current food safety recommendations during pregnancy.
AB  - OBJECTIVES: To better understand pregnant women's food safety attitudes and
      beliefs that affect food selection, preparation and handling behaviors, sources
      of food safety information, motivators and barriers to adopting current
      recommendations, and preferences for receiving food safety materials. METHODS:
      Eleven focus groups were conducted with 69 women (57 pregnant and 12 less than 6
      months postpartum). The Health Belief Model guided development of the moderator's
      guide. In the presence of each focus group, participants completed a food safety
      attitude/behavior questionnaire. Sessions were audiotaped, transcribed, and
      analyzed for common themes across and within groups. RESULTS: Most participants
      indicated moderate concern about food safety and had made some food handling or
      consumption changes since becoming pregnant; however, many were not following 7
      of the 12 specific recommendations discussed. Further, there was resistance to
      change habits, especially for less well-known recommendations. The women assumed
      their food is safe, and wanted strong evidence regarding why they should change
      current practices. Common barriers included lack of prior awareness of most
      recommendations, no prior illness from implicated foods and the convenience,
      perceived health benefits of, and personal preference for many risky foods
      discussed. Participants wanted food safety information that was quick and easy to
      read, sufficiently thorough, and specifically targeted to pregnant women.
      CONCLUSIONS: The women studied had not internalized the connection between risky
      food consumption during pregnancy and risk to the unborn child, but expressed
      interest in valid information that might cause them to change their behaviors.
      The information gained will be useful in developing food safety educational
      materials for pregnant women.

PMID- 15499872
TI  - Physical activity patterns and maternal well-being in postpartum women.
AB  - OBJECTIVE: To examine changes in activity prepregnancy to postpartum; examine
      postpartum activity and sociodemographic predictors of maternal well-being; and,
      examine maternal well-being in subjects on the basis of sport/exercise activity
      prepregnancy to postpartum. METHODS: Ninety-one postpartum women completed a
      Kaiser Physical Activity Survey (KPAS) Ainsworth BE, Sternfeld B, Richardson MT,
      Jackson K. Evaluation of the Kaiser Physical Activity Survey in women. Med Sci
      Sports Exerc 2000; 32:1327-38. and the Lederman Postpartum Questionnaire (PPQ)
      Lederman RP, Weingarten CT, Lederman E. Postpartum self-evaluation questionaire:
      Measures of maternal adaptation. In: Raff BS, Carrol P, editors. Perinatal
      parental behaviour: Nursing research and implications for newborn health. New
      York: Alan R. Liss, 1981:201-31. Subjects recalled activity prepregnancy and
      postpartum for the KPAS indexes that included household/care giving (HC), active
      living habits (AL), occupation (0), and sports/exercise (SE). The PPQ has seven
      well-being subscales. RESULTS: Subjects with older infants or no other children
      increased HC and decreased O prepregnancy to postpartum compared to subjects with
      younger infants or > or =1 other child. Predictors of the variance in the PPQ
      subscales included SE and AL (21% in subscale one), SE (6.0% in subscale two), HC
      (5.3% in subscale three), socioeconomic status (19.7% in subscale four), O (5.0%
      in subscale five), education (5.2% in subscale seven). Subjects who maintained or
      increased SE showed better well-being as compared to subjects who reported no SE
      or decreased SE prepregnancy to postpartum. CONCLUSIONS: In this group of women,
      subjects with older infants or no other children reported higher HC and lower O
      prepregnancy to postpartum. Postpartum SE, education, and socioeconomic status
      were predictors of maternal well-being. In general, better maternal well-being
      was found among subjects maintaining or increasing SE compared to no SE or
      decreased SE prepregnancy to postpartum. Support from partner/husband, family,
      and friends were significant factors in maintaining or increasing SE.

PMID- 15499873
TI  - How children with special health care needs affect the employment decisions of
      low-income parents.
AB  - OBJECTIVES: To better understand the impact of having a child with special health
      care needs (CSHCN), on low-income parents' employment decisions. METHODS: Using
      data from the 1999 and 2000 National Health Interview Survey (NHIS), we estimate
      multivariate statistical regressions (logit and tobit models) to estimate the
      relationship between having a CSHCN and the likelihood of employment and hours of
      employment for a sample-of low-income single parents. RESULTS: Controlling for
      differences in demographic and family characteristics, we find no significant
      association between having a CSHCN and the probability of work or the number of
      hours worked among low-income single-parent families. Separate analysis of
      different dimensions of special health care needs shows that parents of children
      with activity limitations are significantly less likely to work and work fewer
      hours. This result does not hold true for the group of children defined based on
      elevated or special service use, or for the group of children with specific
      chronic conditions. CONCLUSIONS: These results indicate that only a specific
      subset of children with special needs present difficulties for low-income
      parents' work. This suggests that policies to help low-income single parents of
      children with disabilities move into work should target this specific subset of
      children with special health care needs.

PMID- 15499874
TI  - The National Survey of Children's Health: a new data resource.
AB  - CONTEXT: Federal and state maternal and child health programs are responsible for
      promoting and improving the health and well-being of children. To support
      achievement of this goal, the federal Maternal and Child Health Bureau (MCHB) in
      partnership with the National Center for Health Statistics (NCHS), Centers for
      Disease Control and Prevention has developed a new survey that will provide
      uniform national and state data on the health and well-being of children, as well
      as the characteristics of their families and neighborhoods. PURPOSE: The National
      Survey of Children's Health was designed to produce reliable and representative
      state- and national-level estimates for Healthy People 2010 national prevention
      objectives, for each state's Title V needs assessment, and for Title V program
      planning and evaluation. In addition, it will provide a new data resource for
      researchers, advocacy groups, and other interested parties. It is anticipated
      that this survey will be repeated periodically, making trend analysis possible.
      METHODS: This survey was conducted using the State and Local Area Integrated
      Telephone Survey (SLAITS) mechanism, which shares the random-digit-dial sampling
      frame of the National Immunization Survey (sponsored by the National Immunization
      Program and NCHS). Using the SLAITS platform, interviews on approximately 2000
      children were conducted in each state and the District of Columbia. The parent or
      guardian most knowledgeable about the child completed a battery of questions on
      health and development, health insurance coverage, access to care, utilization of
      health care services, presence of a medical home, family functioning, parental
      health, and neighborhood characteristics. Data collection began in January 2003
      and continued through April 2004. Summary reports and electronic data files will
      be available to the public by early 2005. CONCLUSION: This is the second state
      and national survey jointly completed by MCHB and NCHS. It is designed to
      complement the 2001 National Survey of Children with Special Health Care Needs by
      providing data on the health of the general child population.

PMID- 15499875
TI  - At second glance: employers and employees with learning disabilities in the
      Americans with Disabilities Act era.
AB  - The impact of the Americans with Disabilities Act (ADA) of 1990 on the American
      workplace is examined. The findings of a previous study (Gerber, 1992) on
      employer knowledge about learning disabilities are compared to current findings.
      Important themes and employer beliefs and practices that were consistent in
      employer responses are described. Although employers are continuing to make
      efforts to comply with the regulations of the ADA, they still have relatively
      little knowledge or experience with it in terms of learning disabilities.

PMID- 15499876
TI  - The relationship between instructional and assessment accommodations in an
      inclusive state accountability system.
AB  - We investigated the kinds of instructional and assessment accommodations students
      with disabilities receive, and the extent to which instructional accommodations
      match assessment accommodations. Most students who had IEPs in specific content
      areas received instructional accommodations in those areas, and there were no
      differences by disability type. We provide data on the specific types of
      accommodations used. Overall, students' assessment accommodations matched their
      instructional accommodations, though many students received testing
      accommodations that had not been received in instruction. Implications are
      discussed for IEP teams who make decisions about instructional and assessment
      accommodations.

PMID- 15499877
TI  - Treatment outcomes for students with learning disabilities: how important are
      internal and external validity?
AB  - This study analyzed the magnitude of experimental intervention outcomes as a
      function of violations in internal and external validity for studies that
      included students with learning disabilities. The results indicated that
      treatment outcomes were significantly affected by the following violations:
      teacher effects, establishing criterion levels of instructional performance,
      reliance on experimental measures, using different measures between pretest and
      posttest, using a sample heterogenous in age, and using incorrect units of
      analysis. Furthermore, the underreporting of information related to ethnicity,
      locale of the study, psychometric data, and teacher applications positively
      inflated the magnitude of treatment outcomes. A weighted hierarchical regression
      analysis revealed that composite scores of the aforementioned high-risk variables
      accounted for 16% of the total variance in effect size. The implications for
      interpreting intervention research to practice are discussed.

PMID- 15499878
TI  - Are mathematics disabilities due to a domain-general or a domain-specific working
      memory deficit?
AB  - The relationship between verbal and visual-spatial working memory and
      mathematical computation skill was examined in children and adults with and
      without disabilities in mathematics. A hierarchical regression analysis showed
      that, when partialing for the influence of reading ability, age, and gender,
      mathematical computation was better predicted by verbal than by visual-spatial
      working memory. Furthermore, the results showed that the relationship between
      mathematics ability and working memory were not significantly moderated by age
      but were stable across a broad age span. We concluded that, regardless of age,
      deficits in mathematics are mediated by both a domain-general and a domain
      specific working memory system.

PMID- 15499879
TI  - A subgroup analysis of working memory in children with reading disabilities:
      domain-general or domain-specific deficiency?
AB  - The purpose of this study was to investigate whether changes in working memory
      (WM) of children with reading disabilities (RD) were related to a domain-specific
      or a domain-general system. Based on Daneman and Carpenter's (1980) Sentence
      Listening Span task, children were subgrouped into a group of high executive
      processing (high listening span) children without RD, a group of low executive
      processing (low listening span) children with RD, and a group of children with
      and without RD matched on executive processing (moderate listening span).
      Subgroups were compared on phonological, visual-spatial, and semantic WM tasks
      across initial (no probes or cues), gain (cues that bring performance to an
      asymptotic level), and maintenance conditions (asymptotic conditions without
      cues). The results showed that (a) children without RD high in executive
      processing ability outperformed all other subgroups, (b) the RD subgroup low in
      executive processing performed poorly relative to all other subgroups across task
      and memory conditions, (c) children with and without RD matched on executive
      processing were comparable in WM span and changes in WM for all tasks, and (d) WM
      performance of children with RD was a strong linear function of the high
      executive processing group, suggesting that the nature or the specific
      componential makeup of the tasks are not the main contributors to WM performance.
      Taken together, the results suggest that a domain-general system may partially
      contribute to poor WM in children with RD, and that this system may operate
      independently of their reading deficits.

PMID- 15499880
TI  - Do students with and without lexical retrieval weaknesses respond differently to
      instruction?
AB  - Deficits in phonological processing are theorized to be responsible for at least
      some reading disabilities. A considerable amount of research demonstrates that
      many students can be taught one of these phonological processes-phonemic
      awareness. However, not all students have responded favorably to this
      instruction. Research has suggested that these nonresponders may be unable to
      retrieve phonological codes quickly from long-term memory. The purpose of this
      study was to examine whether such a deficiency, which we refer to as lexical
      retrieval weakness, blunts the effectiveness of combined phonemic awareness and
      decoding training. To this end, we compared the effectiveness of phonemic
      awareness and decoding training for students with and without severe lexical
      retrieval weaknesses. All students in both groups demonstrated poor phonemic
      awareness. The results suggested that students with relatively strong lexical
      retrieval skill responded more favorably to beginning reading instruction than
      did students with weak lexical retrieval skill. In other words, lexical retrieval
      weakness may influence reading development independently of the effects of
      phonemic awareness. Implications for instruction are discussed.

PMID- 15499881
TI  - Neuropsychological treatment of dyslexia in the classroom setting.
AB  - The purpose of this study was to validate Bakker's (1990, 1992) clinical
      neuropsychological balance model of dyslexia when implemented in a traditional
      general education classroom environment. The sample included 45 middle school,
      right-handed boys and girls (mean age = 12.78) with L-type dyslexia (excessively
      fast readers who make substantive reading errors), P-type dyslexia (displaying
      accurate but slow and laborious reading), and M-type dyslexia (readers who commit
      a combination of L-type and P-type dyslexia errors). The experimental groups (L
      and P type dyslexia) were presented with hemisphere specific stimulation (HSS)
      and hemispheric alluding stimuli (HAS). HSS involves the presentation of words
      into the right visual field (RVF) or the left visual field (LVF) or through
      tactile exercises with the right or left hand. HAS is achieved by constructing
      semantically and phonetically challenging letters and words. The children with M
      type dyslexia served as a control group and received traditional decoding and
      comprehension exercises. The readers were exposed to a specific treatment model
      for 16 weeks, depending on their reading accuracy and comprehension. Statistical
      analyses indicated that, although there were no significant changes in word
      recognition for the dyslexia subtypes, the readers with L-type, P-type, and M
      type dyslexia exhibited significant improvement in reading accuracy and
      comprehension as assessed by results from pretest to posttest. These results
      suggest that Bakker's clinical neuropsychological intervention can be effectively
      applied to the general education setting as well.

PMID- 15499882
TI  - The utility of kindergarten teacher ratings for predicting low academic
      achievement in first grade.
AB  - The purpose of this study was to assess the predictive value of kindergarten
      teachers' ratings of pupils for later first-grade academic achievement.
      Kindergarten students were rated by their teachers on a variety of variables,
      including math and reading performance, teacher concerns, and amount of learning
      relative to peers. These variables were then analyzed with respect to outcome
      measures for math and reading ability administered in the first grade. The
      teachers' ratings of academic performance were significantly correlated with
      scores on the outcome measures. Analyses were also carried out to determine
      sensitivity, specificity, and predictive values of the different teacher ratings.
      The results indicated high overall accuracy, sensitivity, specificity, and
      negative predictive value for the ratings. Positive predictive value tended to be
      lower. A recommendation to follow from these results is that teacher ratings of
      this sort be used to determine which children should receive cognitive screening
      measures to further enhance identification of children at risk for learning
      disability. However, this recommendation is limited by the lack of empirically
      supported screening measures for math disability versus well-supported screening
      tools for reading disability.

PMID- 15499883
TI  - The possible relationship between visual deficits and dyslexia: examination of a
      critical assumption.
AB  - Numerous studies have found that visual deficits are associated with dyslexia.
      The prevailing theory regarding this association is that dyslexia is the result
      of a deficit in the magnocellular system (earlier called the transient system) in
      the visual pathway. An essential assumption of this theory is that the
      parvocellular system (formerly called the sustained system) is suppressed by the
      magnocellular system at the time of saccadic eye movements. This assumption is
      examined on the basis of published studies of saccadic suppression. The evidence
      from six studies indicates quite unequivocally that the magnocellular system, not
      the parvocellular system, is suppressed during saccadic eye movements. It seems,
      therefore, that an essential premise of the magnocellular deficit theory of
      dyslexia is incorrect.

PMID- 15499884
TI  - Self-organization of mother-child instructional dyads and later attention
      disorder.
AB  - Instructor-learner interactions are viewed from the perspective of dynamically
      self-organizing, coordinated systems. Mothers were asked to instruct their
      preterm and full-term 24-month-old children to sort blocks according to size and
      color (a challenging task for children of this age). Dyads were observed for
      their ability to find a mutual and stable instructional relationship. Dyads in
      which the child was later identified as having attention-deficit/hyperactivity
      disorder (ADHD) were marked by significantly less stable organization, less
      mutuality, and greater perturbations in the system. Mothers of children later
      found to have ADHD tended to apply stronger constraints than those whose children
      grew up to have no identified school problems. Implications are drawn for optimal
      instruction of children who are at risk for central nervous system disorders.

PMID- 15499885
TI  - Language problems in children with learning disabilities: do they interfere with
      maternal communication?
AB  - In this study, parent-child interaction in two carefully matched subgroups-school
      age boys with learning disabilities (LD) who showed a discrepancy between their
      verbal IQ and performance IQ and had more extensive difficulties in higher-level
      language abilities (VIQ < PIQ, n = 8) and boys with LD who did not manifest a
      discrepancy between verbal IQ and performance IQ (VIQ = PIQ, n = 8), were
      investigated. The effects of the child's language problems on child task
      performance and on the quality of maternal communication were analyzed in a
      mother-child problem solving task. Children in the VIQ < PIQ group were found to
      be less successful on the task than children in the VIQ = PIQ group, and their
      mothers exhibited lower communication clarity in their instructions than the
      mothers of the children in the VIQ = PIQ group. An interesting interaction effect
      was found for communication deviances. For mothers in the VIQ < PIQ group the
      extent of deficient communication increased from the monologue to the dialogue
      situation, whereas communication deviances decreased for mothers in the VIQ = PIQ
      group. Three possible models are discussed in light of the differences between
      the subgroups.

PMID- 15499886
TI  - The differential effects of two systematic reading comprehension approaches with
      students with learning disabilities.
AB  - This study compared two highly dissimilar approaches for teaching students to
      determine character motive when reading three types of narrative text. The three
      text types used were textually explicit, textually implicit, and scriptually
      implicit. The two approaches were an explicit rule-based instruction approach and
      a basal-reader activity-based approach. Forty students with learning disabilities
      were randomly assigned to either the explicit rule-based or the basal-reader
      activity-based instructional group. Daily instructional sessions lasted 45
      minutes and were conducted for 2 weeks. The groups were evaluated on four
      comprehension measures: (a) daily retells of stories, (b) unit tests, (c) a
      transfer measure, and (d) a maintenance measure. The results suggest that rule
      based instruction is superior to an activity-based approach when teaching
      students with learning disabilities to determine character motives irrespective
      of text type on short-term measures. However, there were no significant
      differences between the two instructional groups on the maintenance and transfer
      tests.

PMID- 15499887
TI  - Imagery deficits in nonverbal learning disabilities.
AB  - This study reports the observations gathered from 11 children referred to
      consulting services because of learning difficulties at school and diagnosed with
      nonverbal learning disabilities (NVLD). These children had an average verbal IQ,
      but a WISC-R performance IQ lower than the verbal IQ by at least 15 points and
      experienced difficulties especially in mathematics and drawing. The children
      completed a battery of four tasks requiring visuospatial working memory and
      visual imagery: a memory task composed of pictures and their positions (Pictures
      task), a task that required them to memorize the positions filled in a matrix
      (Passive Matrix task), a task that required them to imagine a pathway along a
      matrix (Active Matrix task) and a task that required them to learn groups made up
      of three words, using a visual interactive imagery strategy (TV task). In
      comparison to a control group of 49 children, children with NVLD scored lower in
      all the tasks, showing deficits in the use of visuospatial working memory and
      visual imagery. By contrasting subgroups of children of different ages in the
      control group, it was possible to show that some tasks did not show a clear
      developmental trend. Thus the deficits shown by the children with NVLD cannot
      simply be attributed to a developmental delay of these children, but seem to
      reflect a more severe disability.

PMID- 15499888
TI  - Visual processing of verbal and nonverbal stimuli in adolescents with reading
      disabilities.
AB  - This study investigated whether a group of children with reading disabilities
      (RD) were slower at processing visual information in general (compared to a group
      of children of comparable age and a group of children of comparable reading
      level), or whether their deficit was specific to the written word. Computerized
      backward masking and temporal integration tasks were used to assess the speed of
      visual information processing. Stimulus complexity (simple, complex) and type
      (verbal, nonverbal) were varied, creating a 2 x 2 matrix of stimulus conditions:
      simple nonverbal, complex nonverbal, simple verbal, and complex verbal.
      Adolescents with RD demonstrated difficulties in processing rapidly presented
      verbal and nonverbal visual stimuli, although the effect was magnified when they
      were processing verbal stimuli. Thus, the results of this study suggest that some
      youth with reading disabilities have visual temporal processing deficits that
      compound difficulties in processing verbal information during reading.

PMID- 15499889
TI  - A 10-year follow-up survey of programs and services for students with learning
      disabilities in graduate and professional schools.
AB  - This 10-year follow-up study compares programs and services for students with
      learning disabilities (LD) in graduate and professional schools between 1985 and
      1995. In 1995, surveys were sent to the same institutions (n = 682) as in the
      earlier survey, with a response rate of 30.6%. Significant changes over the 10
      years include a higher level of awareness about LD and evidence of greater
      compliance with Section 504, a greater specificity of assessments required for
      the identification of students who receive services, improvements in the types
      and extent of services available, and increased program visibility. Despite these
      positive changes, 24% of the respondents indicated that they did not have a
      coordinator for LD at their institution, and 33% did not have a written plan for
      services. Eighteen institutions with programs or services for students with LD
      gave permission to publish their names. Implications and recommendations are
      discussed.

PMID- 15499890
TI  - ADHD: a psychological response to an evolving concept. (Report of a Working Party
      of the British Psychological Society).
AB  - The British Psychological Society is the only national organization of
      psychologists within the United Kingdom representing all aspects of psychology
      and all subspecialisms within psychology. It is both a learned scientific society
      and a professional association. To address the concept of attention
      deficit/hyperactivity disorder (ADHD), the Professional Affairs Board of the
      Society convened a Working Party, consisting of individuals nominated by
      subsystems of the Society because of their recognized professional and academic
      expertise. They covered a range of specialisms, including educational, clinical,
      criminological, neurological, and cognitive psychology. A report by the Working
      Party was published in September 1996. It had two main aims: first, to outline
      the research that was relevant to current understanding of the notion of ADHD
      from an historical, psychological, and biological perspective, and, second, to
      consider implications for practice in the light of the information obtained. The
      focus was predominantly on children, although it was recognized that problems
      could persist into adulthood. The intention was to write a report for
      professionals that also would be accessible to a wider audience. This article is
      a highly abridged version of the report. It omits the references to research
      reviews and research studies contained in the full account. Selected extracts are
      included in order to justify the conclusions and the recommendations that are
      made and to inform a North American audience of developments in the United
      Kingdom.

PMID- 15499891
TI  - The social determinants of cancer.

PMID- 15499892
TI  - Suicide in the French armed forces.
AB  - Several states, of whom France, have been alarmed about suicide in the military.
      An observational longitudinal cohort study was conducted to check whether the
      suicide risk in the French army was higher than in the general population and to
      find out the more prone to self-harm destruction personnel categories. From 1997
      to 2000 inclusive, 230 suicides occurred among 315,934 person.years; i.e., the
      overall annual crude suicide rate was 18.2 per 100,000 active-duty personnel.
      With the National data for 1999 as reference, army men had a lower suicide risk
      than men in the overall population of similar age categories (standardised
      mortality ratio = 67). A Poisson regression model showed that the incidence rate
      in the Gendarmerie was twice as high as in the Land Forces (incidence rate ratio
      = 2.15), that the incidence relative risk increased threefold over 4 years, and
      that the incidence rate ratio amongst under 25 and from 40 to 44-year-old
      personnel was almost twice as high as in the 25-29-year-old category. The main
      suicide methods were use of a firearm (51%) and hanging (28%). Despite a global
      lower risk than in the general population, certain army categories, i.e.,
      Gendarmerie personnel and young men, deserve specific surveillance and preventive
      measures.

PMID- 15499893
TI  - Regional variability in population acute myocardial infarction cumulative
      incidence and mortality rates in Spain 1997 and 1998.
AB  - BACKGROUND: Myocardial infarction (MI) incidence and mortality display a high
      geographic variation. AIMS: The objective of the present study was to analyze MI
      mortality, cumulative incidence rate variability in seven regions of Spain from
      1997 to 1998. METHODS AND RESULTS: Standardized methods were used to identify,
      find, register, and classify MI cases that were classified as definite, possible,
      insufficient-data MI, and non-MI. The total population of the seven monitored
      regions was 7,364,682 inhabitants. Of the 11,256 cases fulfilling eligibility
      criteria to investigate, 10,660 were selected to calculate MI rates: 6554 (61.5%)
      non-fatal definite MI, 1179 (11.1%) fatal definite MI, 1859 (17.4%) fatal
      possible MI, 1068 (10.0%) fatal cases with insufficient data. The IBERICA 25-74
      years age-standardized cumulative incidence rates for men and women, were 207
      (range: 175-252) and 45 (range: 36-65) per 100,000, respectively. The age
      standardized mortality rates for men and women, were 73 (range: 62-94) and 20
      (range: 13-29) per 100,000, respectively. Age-standardized case-fatality was 31.4
      and 24.2% in men aged 25-74 and 35-64 years, respectively, and 32.7 and 27.0%,
      respectively, in women. CONCLUSIONS: MI cumulative incidence and mortality rates
      are low compared with other industrialized countries but, vary considerably among
      regions in a Mediterranean country like Spain.

PMID- 15499894
TI  - Influence of asthma on the validity of reported lifelong environmental tobacco
      smoke in the EGEA study.
AB  - The aim of this study was to assess the short-term reproducibility and the
      validity of reported ETS (environmental tobacco smoke) exposure, with a special
      emphasis on the potential misclassification related to personal or family history
      of asthma. Analyses were based on the data on the Epidemiological study on the
      Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy
      (EGEA), a case-control study of asthma that included first degree relatives of
      asthmatic cases. The study was comprised of 348 families of asthmatics recruited
      in six chest clinics throughout France and 416 population-based controls. For
      studying the validity of ETS reports, personal active smoking histories reported
      by family members were taken as reference. The reproducibility of ETS exposure
      report was good, and independent of asthma. The validity of the report of
      maternal and paternal smoking in childhood and spouse smoking during life was
      high (overall agreement > or = 84%). Mothers of asthmatic children significantly
      underreported their smoking habits when questioned on their children's passive
      tobacco exposure. Offspring of parents who had stopped smoking underestimated
      their ETS exposure in childhood. In conclusion, interviews with mothers on their
      personal active smoking habits may provide a more accurate estimate of their
      asthmatic child's passive exposure than asking mothers specifically about their
      children's passive exposure. There was no indication that asthma status (either
      of the parent/spouse or of the respondent) by itself influences the report of ETS
      exposure during childhood or adulthood.

PMID- 15499895
TI  - Psychological distress in hospitalized patients with chronic obstructive
      pulmonary disease.
AB  - OBJECTIVES: To investigate the prevalence of psychological distress in
      hospitalized patients with chronic obstructive pulmonary disease (COPD), and to
      examine possible associations between psychological distress and several
      sociodemographic variables. METHODS: The Hopkins Symptom Checklist was used to
      gather data from 92 hospitalized COPD patients. These data were compared with
      3,319 respondents aged 45 or over drawn from the 1998 Norwegian Statistics Health
      Survey. The latter were divided into four groups: respondents with COPD,
      respondents with other respiratory diseases, respondents with mixed chronic
      diseases, and a healthy group. RESULTS: The prevalence of psychological distress
      was found to be 58.7% in the hospitalized COPD patients and 42.9% in the
      community-based COPD sample. After controlling for sociodemographic variables and
      current smoking, the results showed a higher risk of psychological distress among
      hospitalized COPD patients (OR = 23.69; 95% CI: 13.37-41.98) and the community
      based COPD sample (OR = 18.16; 95% CI: 8.31-39.68), and with sub-samples with
      other respiratory diseases (OR = 5.87; 95% CI: 3.82-9.02), and mixed chronic
      diseases (OR = 3.51; 95% CI: 2.39-5.18). CONCLUSIONS: COPD is associated with a
      high prevalence of psychological distress in both hospital and community
      settings. Furthermore, it appears that age, gender, education, marital status,
      and current smoking status do not substantially mediate the association between
      the severity of psychological distress and COPD status. The results provide
      additional evidence of the importance of screening for psychological distress
      symptoms in both hospitalized and community-based patients with COPD.

PMID- 15499896
TI  - Nutrient intakes, nutritional patterns and the risk of liver cirrhosis: an
      explorative case-control study.
AB  - Several experimental studies have suggested that specific nutrients might play a
      role on the risk of liver damage. Nevertheless, few epidemiological studies have
      evaluated the role of diet on the risk of symptomatic liver cirrhosis, giving
      contradictory results. To evaluate the role of the intake of nutritional factors
      and dietary patterns on the risk of symptomatic liver cirrhosis and to examine
      their combined action with alcohol consumption we used data from the Italian
      Study on Liver Cirrhosis Determinants project. From 1994 to 1998 all the
      consecutive cirrhotic inpatients admitted to 19 Italian collaborative hospitals
      for signs of liver decompensation in whom the diagnosis of liver cirrhosis was
      made for the first time (259 cases) and one or two gender, age and area of
      residence matched individuals (416 controls) were recruited. Data on lifetime
      alcohol intake, usual consumption of 191 food items and on markers of hepatitis B
      and C viral infection were collected. The analysis of principal components
      identified a nutritional pattern positively correlated with vegetable and fruit
      intakes and negatively with animal and no-fruit sugar products. With respect to
      abstainers, relative risks in consumers of use < or = 25 and > or = 51 g/day of
      alcohol increased from 0.4 [95% confidence interval 0.0, 5.9] to 9.3 [1.3, 69.0]
      and from 2.1 [1.1, 4.2] to 18.1 [2.8, 118.3] for the lowest and the highest value
      of this nutritional pattern, respectively. Diet might therefore modulate the
      damaging effect of alcohol on the liver.

PMID- 15499897
TI  - High seroprotection rate induced by intradermal administration of a recombinant
      hepatitis B vaccine in young healthy adults: comparison with standard
      intramuscular vaccination.
AB  - Intradermal (ID) vaccination has been proposed as a cost-saving alternative for
      administration of Hepatitis B (HB) vaccine to implement of mass vaccination of
      high-risk groups, particularly in developing countries. Therefore, the
      effectiveness of ID vaccination needs to be evaluated and verified in different
      ethnic backgrounds. The present study is a randomized trail using a recombinant
      vaccine (Heberbiovac) to compare immunogenecity and safety of an intradermal low
      dose (4 microg) with standard dose (20 microg) of intramuscular (IM) vaccination
      in healthy Iranian population. Participants were 143 healthy Iranian medical and
      nursing students randomly allocated to ID or IM vaccination group. The vaccine
      was inoculated at 0, 1 and 6 months intervals. Serum samples were collected 1
      month after the last vaccination and the anti-HBs response was determined using
      ELISA. The overall seroprotection rate (anti-HBs level > or = 10 IU/L) was 97.3%
      for ID vaccination group, which was not different from that of IM vaccination
      group (98.55%) (p = 0.99). Similarly, geometric mean titers (GMT) of anti-HBs
      were not significantly different between ID (1164.1 IU/L) and IM (1071.8 IU/L)
      vaccination groups (p = 0.4). There was no significant difference in
      seroprotection rate and GMT of anti-HBs between sexes. Although induration and
      hyperpigmentation at the site of injection were more frequently observed in ID
      vaccination group, no other clinically adverse effects were observed in both
      vaccination groups. We conclude that the ID route, which would require one-fifth
      of the standard dose, would be suitable for use in certain groups such as high
      risk adults when the cost of vaccine is the inhibiting factor for mass
      vaccination.

PMID- 15499898
TI  - Does co-infection with Giardia lamblia modulate the clinical characteristics of
      enteric infections in young children?
AB  - BACKGROUND: Giardia lamblia (G. lamblia) is a prevalent enteric pathogen causing
      both asymptomatic carriage and diarrheal illness among children worldwide. In
      this study we examined the hypothesis that G. lamblia may modulate the effect of
      other enteric pathogens during concurrent infection. METHODS: Bedouin (n = 238)
      infants were followed from birth to ages 18-23 months. Morbidity was ascertained
      by weekly home interviews and infant's stools were collected fortnightly. The
      risk for and severity of diarrheal disease were compared between episodes caused
      by enteric pathogens other than G. lamblia alone and G. lamblia-mixed episodes.
      RESULTS: In 59 of 293(20.1%) diarrhea episodes two or more pathogens were
      detected. In two thirds of the mixed episodes G. lamblia was involved. Neither
      the incidence of diarrhea nor the mean diarrheal episode duration differed
      between follow up months in which G. lamblia was or was not detected, when age
      specific or age adjusted values were compared. There were no differences in
      severity of episodes for single or G. lamblia-mixed infections except for
      rotavirus. Episodes with rotavirus alone were more severe as compared to episodes
      where co-infection with G. lamblia was found. CONCLUSIONS: The results of this
      study do not confirm the hypothesis that G. lamblia modulates the clinical effect
      of infection with other enteric agents. However, the findings of the change in
      severity of infection with rotavirus suggest that this question warrants further
      investigation.

PMID- 15499899
TI  - Three-year (1999-2002) of epidemiological and virological surveillance of
      influenza in north-east Italy.
AB  - The results of the epidemiological and virological surveillance of influenza
      performed during the 1999/2000, 2000/2001 and 2001/2002 seasons in the
      northeastern Italy were presented and the relationship between age-specific
      morbidity rates and circulating strains were discussed.The epidemiological
      findings pointed out a change in age distribution. During the 1999/2000 season,
      characterized by a circulation of viruses antigenically close to the vaccine
      strain, a similar incidence rate in the 0-14 and 15-64-year-old groups was
      observed, while during the 2001/ 2002 winter the virus infected mostly children.
      During 2001/2002 season, B type viruses predominated with at least three
      distinguishable molecular variants. In particular, B/Victoria/2/87-like viruses
      re-emerged after more than a decade, and the antibodies elicited by the vaccine
      strain and by the strains circulating in previous seasons were poor or not
      protecting. The accumulation of susceptible subjects in young age group during
      the 1990s, due to the lack of circulation of B/Victoria/2/87-like viruses, was
      responsible for the unusual morbidity in the 0-14 year group. No circulation of
      B/Victoria/2/87-like viruses was observed in > 64-year-old group during 2001/2002
      epidemic, probably due to a long-lasting immunity against viruses belonging to
      this lineage.

PMID- 15499900
TI  - Re-emergence of measles among young adults in Marseilles, France.
AB  - A total of 89 cases of measles were diagnosed in southeastern France between
      January and June 2003. Nation-wide epidemiological investigations suggested that
      this outbreak was restricted to southeastern France, and most likely reflected
      the endemic circulation of measles virus due low vaccination coverage. Genetic
      analysis identified genotype D7 strains as the cause of the outbreak.

PMID- 15499902
TI  - Effects of spermidine synthase overexpression on polyamine biosynthetic pathway
      in tobacco plants.
AB  - Transgenic tobacco plants overexpressing the Datura stramonium spermidine
      synthase (EC 2.5.1.16) cDNA were produced in order to understand the role of this
      gene in the polyamine metabolism and in particular in affecting spermidine
      endogenous levels. All the analysed transgenic clones displayed a high Level of
      overexpression of the exogenous cDNA with respect to the endogenous spermidine
      synthase. No relationship was detected between the mRNA expression level of S
      adenosylmethionine decarboxylase (SAMDC, EC 4.1.1.50), which did not change
      between the negative segregant control and the transgenic plants, and spermidine
      synthase, suggesting the existence of an independent regulatory mechanism for
      transcription of the two genes. The determination of enzyme activities indicated
      an increased spermidine synthase and S-adenosylmethionine decarboxylase activity,
      with the last being mainly recovered in the particulate fraction. ODC (ODC, EC
      4.1.1.17) was the most active enzyme and its activity was equally distributed
      between the soluble and the particulate fraction, while ADC (ADC, EC 4.1.1.19)
      activity in the transgenic plants did not particularly change with respect to the
      controls. In comparison to the controls, the transformed plants displayed an
      increased spermidine to putrescine ratio in the majority of the clones assayed,
      white the total polyamine content remained almost unchanged. These findings
      suggest a high capacity of the transformed plants to tightly regulate polyamine
      endogenous levels and provide evidence that spermidine synthase is not a limiting
      step in the biosynthesis of polyamines.

PMID- 15499901
TI  - The Wheezing Illnesses Study Leidsche Rijn (WHISTLER): rationale and design.
AB  - The Wheezing Illnesses Study Leidsche Rijn (WHISTLER) was initiated in December
      2001 as a single-centre prospective birth cohort study and will include a
      population-based sample of at least 2000 healthy newborns. The aims of WHISTLER
      are to investigate determinants for wheezing illnesses (including neonatal lung
      function, viral infections, asthma-susceptibility genes and endotoxin exposure)
      and to derive a comprehensive risk score, that is appropriate for use in primary
      health care and allows for efficient planning of early preventive strategies.
      Baseline examination includes a questionnaire evaluating known risk factors for
      wheezing illnesses; anthropometric measurements; measurements of infant and
      parental lung function; and sampling of infant and parental DNA. Participants
      will be followed for respiratory events using data from a daily respiratory
      symptom questionnaire; visits to the general practitioner (primary health care
      visits, drugs prescriptions and hospital referral); viral sampling during
      wheezing episodes; and house dust sampling. Based on actual neonatal care
      practice and embedded in a larger epidemiological study, the Utrecht Health
      Project, WHISTLER will provide an unique framework to address issues in childhood
      respiratory disease that are currently insufficiently understood. In particular,
      WHISTLER will provide a well-balanced view on the prognostic power of neonatal
      lung function and genetic and environmental factors (including viral infections
      and endotoxin exposure) to predict wheezing illnesses from birth to young
      adulthood and beyond. In the scope of prevention, WHISTLER is expected to support
      the design of solid based prevention measures to reduce respiratory morbidity,
      mortality and associated costs, and to improve quality of life.

PMID- 15499903
TI  - Diurnal O2 and carbohydrate levels in wheat kernels during embryony.
AB  - In vitro zygotic and somatic embryogenesis procedures for wheat have been
      improved by simulating in ovulo nutritional, hormonal and dissolved oxygen (dO2)
      conditions. However, diurnal fluctuations in these conditions during early
      embryony are not well characterized. In this study, dO2 and water-soluble
      carbohydrate Levels in wheat kernels were determined after 8 h of light and 8 h
      of dark at approximately 6, 12 and 18 day post anthesis (DPA). Clark style O2
      microelectrodes, having a tip diameter of approximately 115 microm, were inserted
      into intact kernels immediately distil to the developing embryo, and dO2 levels
      were recorded at 50 microm intervals into the center of kernels. High-performance
      anion exchange chromatography with pulsed amperometric detection was used to
      quantify carbohydrate levels in endosperm sap. dO2 levels in the chlorophyllous
      layer of the pericarp reached 190 mmoLm(-3) during the day, which probably
      represents, because of photosynthesis, a supersaturated O2 condition relative to
      the external environment (21% O2). At the embryo surface, dO2 levels at 6 DPA
      ranged from 135 to 170 mmolm(-3). At 12 and 18 DPA, dO2 levels at the embryo axis
      ranged from 100 to 150mmolm(-3). At all three stages, dO2 levels in the center of
      the endosperm were below 13 mmolm(-3). Extreme fluctuations in carbohydrate
      levels were observed diurnally during rapid seed fill (12DPA). Levels of sucrose
      and short-chain fructans were much higher during the day than during the night.
      In contrast, fructose, glucose, and myo-inositol levels were much higher during
      the night than during the day. By 18DPA (hard dough stage), carbohydrate levels
      tended to be similar during the day and night. These dynamic fluctuations may
      assist in regulating embryony in ovulo, and their simulation might improve the
      development of somatic and zygotic embryos in vitro.

PMID- 15499904
TI  - Carbohydrate metabolism in two apple genotypes that differ in malate
      accumulation.
AB  - In the apple variety 'Usterapfel', there are two known genotypes, which differ in
      malic acid content. One hundred days after full bloom, low-acid fruit (LA-fruit)
      contained 125 micromolg(-1) dry matter (DW) of malate, while the high-acid
      genotype (HA-fruit) reached levels up to 627 micromolg(-1) DW. There was no
      difference in the catalytic activity of enzymes involved in malate metabolism,
      such as PEPcarboxylase, malate dehydrogenase, and NADP malic enzyme. After
      [14C]glucose incorporation into the excised tissue of either genotype, the
      organic acid fraction was labeled to approximately the same extent. Furthermore,
      uptake of [14C]malate was significantly lower in excised tissue of LA-fruit.
      These findings suggest that low malate content in LA-fruit is the result of a
      restricted ability to accumulate malate in apple parenchyma cells. The different
      ability to accumulate malate had a pronounced effect on overall carbon
      partitioning. However, the rate of respiration and the rate of malate synthesis
      was similar in both genotypes. In HA-fruit, the glycolytic flux through pyruvate
      kinase was increased to compensate for the carbon that accumulated in the vacuole
      as malate. Since malate storage in the LA-fruit was restricted, it was more
      easily available for gluconeogenesis, and was correlated with a three-times
      higher activity of PEPcarboxykinase. LA-fruit showed higher concentrations of
      ATP, which stimulated Glc6P and fructose-6-phosphate formation. The elevated
      hexosephosphate content led to an enhanced partitioning of carbon into starch
      (+40%), hemicellulose (+104%), and sucrose (+40%) in more mature fruit. The
      activation of carbohydrate synthesis resulted in a significant drop in glucose-1
      phosphate (Glc1P). To meet the increased demand for Glc1P, the activities of
      neutral and acid invertase, hexokinase, and phosphoglucomutase were higher in LA
      fruit. Glucose was a more versatile substrate for this metabolic route than was
      fructose. It was also evident that glycolytic flux in apple was dependent on
      glucose level, and that the reaction catalysed by phosphoglucomutase contributed
      to the regulation of carbon partitioning between malate and carbohydrate
      polymers.

PMID- 15499905
TI  - Partitioning and mobilization of starch and N reserves in grapevine (Vitis
      vinifera L.).
AB  - We followed C and N reserves of grapevines grown in trenches under semi
      controlled conditions over a 3-year period after planting. Temporal mobilization
      of stored C and N and subsequent distribution of reserve materials within the
      vines were described in parallel with 15N uptake, particularly during the third
      growing season. Storage C in the perennial tissues (roots, trunk, canes) was
      mainly made of starch, which accumulated in the ray parenchyma of the wood. In
      the permanent tissues, starch and total nitrogen contents were found to decrease
      early in the development (bleeding sap, budbreak) whereas, on a concentration
      basis, they decreased only after stage 7 (first leaf fully expanded). Starch
      started to accumulate again in the perennial tissues during flowering. The same
      observation was made with total nitrogen, although N levels were much lower than
      those of starch. The 15N study showed that N uptake by the roots started at
      budbreak and increased with vine development, becoming predominant over reserve
      mobilization only after the onset of flowering. Taken together, these results
      indicate that the spring growth period can be divided into three main phases: In
      the first (dormancy to budbreak), significant losses of C and N proceed mainly
      via root necrosis. In the second period (first leaf to the onset of bloom), a
      strong mobilization of starch (and, to a lower extent, of N) occurred for
      supporting vegetative and reproductive growth. At that point, most of the C and N
      reserves used on the spring flush were those of the roots, rather than those of
      the old wood (trunk, canes). In the third period (bloom and early berry
      development), the mobilization process became low and was relieved by N uptake
      (and CO2 assimilation) supplying nutrients to the sink structures.

PMID- 15499906
TI  - Is osmotic adjustment required for water stress resistance in the Mediterranean
      shrub Atriplex halimus L?
AB  - The effect of water stress was investigated in plants from two populations of
      Atriplex halimus L: Tensift issued from a salt-affected coastal area and
      Kairouan, originating from an inland dried site. Water deficit was applied by
      withholding water for 22 days. Shoot dry weight (shoot DW), leaf relative water
      content (RWC), turgid weight to dry weight ratio (TW/DW), osmotic potential
      (psis), osmotic adjustment (OA), proline, glycinebetaine, and sugar content were
      determined 1, 8, 15 and 22 days after withholding watering. Water stress induced
      a decrease in shoot DW, RWC, psis, and TW/DW, but an increase in glycinebetaine
      and sugar leaf contents. The decrease of psis and TW/DW was more marked in
      Kairouan than in Tensift. At the end of the stress period, Kairouan showed a
      greater OA compared with Tensift. However, the contribution of net solute
      accumulation (OAacc) was similar in both populations in response to stress. Water
      stress resistance could thus not be associated with higher OA, although the
      ability of plants to regulate these metabolic and physiological functions could
      play an important role under harmful conditions. The possible roles of osmolyte
      accumulations are discussed in relation to the specific physiological strategy of
      water-stress-resistance in this species.

PMID- 15499907
TI  - The pyridoxal kinase gene TaPdxK from wheat complements vitamin B6 synthesis
      defective Escherichia coli.
AB  - Pyridoxal kinase (EC 2.7.1.35) is a key enzyme in the conversion of vitamin B6 to
      pyridoxal 5'-phosphate (PLP). PLP is the crucial cofactor required by numerous
      enzymes involved in amino acids metabolism. Recently, studies with Arabidopsis
      salt overly sensitive 4 mutants demonstrated that pyridoxal kinase is a novel
      salt tolerance determinant important for the regulation of Na+ and K+ homeostasis
      in plants. We describe here the TaPdxK gene which encodes a pyridoxal kinase,
      cloned from Triticum aestivum by RACE PCR method. The putative amino acid
      sequence of TaPdxK is 78% identical to Arabidopsis AtSOS4. Southern analysis
      suggests that there are at least two copies of pyridoxal kinase genes in wheat
      genome. The expression of TaPdxK cDNAs complements an Escherichia coli mutant
      defective in pyridoxal kinase. TaPdxK transcripts were detected in roots, shoots,
      spikes and anthers by RT-PCR analysis. TaPdxK expression level was not regulated
      by salt, ABA, and osmotic stress.

PMID- 15499908
TI  - Molecular cloning, characterization, tissue-specific and phytohormone-induced
      expression of calcium-dependent protein kinase gene in cucumber (Cucumis sativus
      L.).
AB  - A cucumber cDNA designated CsCPK5 and encoding a calcium-dependent protein kinase
      (CsCDPK5) was isolated and characterized. An open reading frame of 1542 bp was
      detected that could encode a protein of 514 amino acid residues with a calculated
      molecular mass of 56.5kDa. Comparison of the deduced amino acid sequence of
      CsCDPK5 with sequences of other CDPKs revealed the highest similarity (85%) to
      AtCDPK6. As described for other CDPKs, CsCDPK5 has a long variable domain
      preceding a catalytic domain, an autoinhibitory function domain, and a C-terminal
      calmodulin-domain containing 4 EF-hand calcium-binding motifs. The N-terminal
      long variable domain of CsCDPK5 does not contain the N-myristoylation motif,
      which is found in many CDPKs. The relative expression level of the CsCPK genes in
      various organs of cucumber plants and seedlings and in etiolated, excised
      cotyledons and hypocotyls following treatments with light and/or benzyladenine
      (BA), abscisic acid (ABA), gibberellic acid (GA) or indole acetic acid (IAA) was
      determined by northern analysis using the CsCPK5 cDNA probe. The CsCPK
      transcripts are most abundant in cucumber plant Leaves with less accumulation in
      cucumber seedling roots and hypocotyls and lowest Levels in cucumber plant
      flowers and seedling hooks and cotyledons. All phytohormones tested enhanced the
      accumulation of the transcripts 2-3-fold in etiolated cotyledons. On the other
      hand, levels of the transcripts increased to a lesser extent in both light and BA
      or IAA-treated cotyledons and no effect was noted in response to light treatment
      with GA. In hypocotyls, no major changes in the relative levels of CsCPK
      transcripts were observed in the phytohormone-treated etiolated and light-exposed
      tissues, except an up-regulatory effect with IAA treatment in the etiolated and
      IAA, ABA and GA treatments in light-exposed hypocotyls. These observations
      suggest that exogenous phytohormones can up-regulate the CsCPK transcript levels
      in tissue-specific, and light-dependent and independent manners.

PMID- 15499909
TI  - Direct differentiation of somatic embryos on different regions of intact
      seedlings of Azadirachta in response to thidiazuron.
AB  - Direct differentiation of somatic embryos occurs in high-frequency and at high
      density in response to 1.0 microM TDZ, on different regions-hypocotyl, epicotyl,
      cotyledonary-node, cotyledons and leaves-of intact seedlings of Azadirachta. One
      week-old seedlings on this medium exhibited stress symptoms as visible by the
      loss of root formation and reduction in the elongation of hypocotyl and epicotyl.
      Globular somatic embryos were more abundant on hypocotyl, epicotyl, stem tip and
      leaves. The arrest of embryos at this stage was possibly due to their presence in
      high density. Well-developed somatic embryos were present on the cotyledons and
      the cotyledonary-node. These embryos on isolation and transfer to hormone-free
      medium regenerated readily to form plantlets. The possible role of stress in
      thidiazuron-induced somatic embryo formation is discussed.

PMID- 15499910
TI  - Mutant acetolactate synthase gene is an efficient in vitro selectable marker for
      the genetic transformation of Brassica juncea (oilseed mustard).
AB  - We report in this study, the successful deployment of a double mutant
      acetolactate synthase gene (ALSdm, containing Pro 197 to Ser and Ser 653 to Asn
      substitutions) as an efficient in vitro selection marker for the development of
      transgenic plants in Brassica juncea (oilseed mustard). The ALS enzyme is
      inhibited by two categories of herbicides, sulfonylureas (e.g. chlorsulfuron) and
      imidazolinones (e.g. imazethapyr), while the mutant forms are resistant to the
      same. Three different selection agents (kanamycin, chlorsulfuron and imazethapyr)
      were tested for in vitro selection efficiency in two B. juncea cultivars, RLM198
      and Varuna. For both the cultivars, higher transformation frequencies were
      obtained using chlorsulfuron (3.8 +/- 0.6% and 4.6 +/- 0.9% for RLM198 and
      Varuna, respectively) and imazethapyr (10.2 +/- 0.7% for RLM198 and 7.8 +/- 1.2%
      for Varuna) as compared to that obtained on kanamycin (3.1 +/- 0.2% and 2.8 +/-
      0.5% for RLM198 and Varuna, respectively). Additionally, transformation
      frequencies were higher on imazethapyr than on chlorsulfuron for both the
      cultivars indicating that imidazolinones are better selective agents than
      sulfonylureas for the selection of mustard transgenics.

PMID- 15499911
TI  - Stir bar sorptive extraction with in situ derivatization and thermal desorption
      gas chromatography-mass spectrometry in the multi-shot mode for determination of
      estrogens in river water samples.
AB  - A novel method for the trace analysis of natural and synthetics estrogens, such
      as estrone (E1), 17beta-estradiol (E2) and 17alpha-ethynylestradiol (EE), in
      river water sample was developed, which involved stir bar sorptive extraction
      (SBSE) with in situ derivatization followed by thermal desorption (TD)-gas
      chromatography-mass spectrometry (GC-MS). The derivatization conditions with
      acetic acid anhydride and the SBSE conditions such as sample volume and
      extraction time were investigated. In addition, the single and multi-shot modes
      in TD were investigated. The detection limits of E1, E2 and EE in river water
      sample were 0.2, 0.5 and 1 pg ml(-1) (ppt), respectively, in the multi-shot mode
      using five stir bars. The calibration curves for E1, E2 and EE were linear and
      had correlation coefficients >0.99. The average recoveries of E1, E2 and EE from
      all sample volumes were higher than 90% (R.S.D. < 10%) with correction using an
      added surrogate standard such as estrone-13C4, 17beta-estradiol-13C4 or 17alpha
      ethynylestradiol-13C4. This simple, accurate, sensitive and selective analytical
      method may be applicable to the determination of trace amounts of estrogens in
      water samples.

PMID- 15499912
TI  - Automated solid-phase extraction for purification of single nucleotide
      polymorphism genotyping products prior to matrix-assisted laser
      desorption/ionisation time-of-flight mass spectrometric analysis.
AB  - In this article, we describe the application of a novel micro elution solid-phase
      extraction method for purification of short stretches of DNA products of single
      nucleotide polymorphisms (SNPs) prior to MALDI mass spectrometry analysis. An
      important feature of our method is that the purification columns containing a
      copolymer of divinylbenzene and N-vinylpyrrolidone can be used several times
      thereby significantly reducing costs. We implemented this DNA purification
      technology into a fully automated procedure including molecular biology, MALDI
      sample preparation, automated mass spectrometric analysis and SNP allele calling
      by software. Due to the facile purification protocol, the methodology shown could
      furthermore be used for other applications where efficient medium to high
      throughput purification of nucleic acids is required.

PMID- 15499913
TI  - Application of solvent microextraction in a single drop for the determination of
      new antifouling agents in waters.
AB  - A new, rapid microextraction technique termed solvent microextraction (SME) has
      been developed for the simultaneous determination of new generation antifouling
      agents, in water samples. Chlorothalonil, dichlofluanid and Sea nine 211 were
      employed as model compounds to asses the extraction procedure and were determined
      by gas chromatography with electron capture detection. Experimental parameters
      which control the performance of SME, such as selection of solvent, exposure
      time, agitation, organic drop volume, and salt concentration were optimized. The
      new method provided good average enrichment factors of >10.7 for all analytes,
      good precision (RSD < 8.5%) and good linearity (r2 > 0.9880). The limits of
      detection (LODs) were in the range of 0.00025-0.003 microg/L (S/N = 3). The SME
      was performed in different type of natural water samples and acceptable
      recoveries were obtained for the tested analytes. The results demonstrated that
      SME is a rapid, accurate and effective preparation method and could be
      successfully performed for the determination of antifouling agents in water
      samples.

PMID- 15499914
TI  - Effect of the temperature on the isotherm parameters of phenol in reversed-phase
      liquid chromatography.
AB  - Adsorption isotherm data of phenol from an aqueous solution of methanol onto a
      C18-bonded silica (Symmetry-C18) were acquired by frontal analysis (FA) at six
      different temperatures, in a wide concentration range. The non-linear fitting of
      these data provided the bi-Langmuir model as best isotherm model, a conclusion
      further supported by the results of the calculation of the affinity energy
      distribution (AED). The isotherm parameters were obtained using several methods,
      the fitting of FA isotherm data, the calculation of the AED, and the inverse
      method, that uses overloaded elution band profiles. The different values obtained
      are in close agreement. They allow a quantitative investigation of the separate
      properties of the low- and the high-energy sites on the adsorbent surface.
      Increasing the temperature decreases the saturation capacity of the low-energy
      adsorption sites and the adsorption constant of the high-energy sites. In
      contrast, increasing the temperature does not cause any significant changes in
      either the saturation capacity of the high-energy sites or the adsorption
      constant of the low-energy sites.

PMID- 15499915
TI  - Evaluation of apparent formation constants of pentacyclic triterpene acids
      complexes with derivatized beta- and gamma-cyclodextrins by reversed phase liquid
      chromatography.
AB  - A reversed phase HPLC method has been investigated in order to resolve three main
      pentacyclic triterpene acids (oleanolic-, betulinic- and ursolic acid) found in a
      lot of plants. Some of them (oleanolic and ursolic acids) are position isomers
      and their resolution is highly improved by the addition of derivatized
      cyclodextrins in mobile phase. The formation of 1:1 inclusion complexes was
      assumed. Apparent formation constants of triterpene acids with DM-beta-CD and HP
      gamma-CD were determined by HPLC method. Experimental results confirmed the
      complexation model and explained the modification of elution order according to
      the type of cyclodextrin added to the mobile phase. The influence of mobile phase
      organic modifier on apparent formation constants was also investigated. Results
      proved the competition between cyclodextrins hydrophobic cavity and organic
      solvent towards triterpene acids affinity.

PMID- 15499916
TI  - Optimization of binary porogen solvent composition for preparation of butyl
      methacrylate monoliths in capillary liquid chromatography.
AB  - Butyl methacrylate monolithic columns in 320 microm i.d. fused silica capillaries
      for reversed-phase capillary liquid chromatography were prepared by radical
      polymerization initiated thermally with azobisisobutyronitrile (AIBN).
      Polymerization mixture contained butyl methacrylate (BMA) as the function monomer
      and ethylene dimethacrylate (EDMA) as the crosslinking agent with 1,4-butanediol
      and 1-propanol as a binary porogen solvent. Ratio of 1,4-butanediol to 1-propanol
      in the porogen solvent was optimized regarding the monolithic column efficiency
      and performance. Total porosity, column permeability, separation impedance,
      Walters hydrophobicity index, retention factors, peak asymmetry factors, height
      equivalents to a theoretical plate and peak resolutions were used for
      characterization of the prepared monolithic columns. The polymerization mixture
      consisting of 17.8% of BMA, 21.8% of EDMA, 18.0% of 1,4-butanediol, 42.0% of 1
      propanol and 0.4% AIBN generated monolithic columns of the best performance
      having a sufficient permeability and the lowest separation impedance. It was also
      demonstrated that monolithic columns of this composition exhibited good
      preparation reproducibility and an excellent pressure resistance when applied in
      capillary liquid chromatography.

PMID- 15499917
TI  - Development and evaluation of N-hydroxysuccinimide-activated silica for
      immobilizing human serum albumin in liquid chromatography columns.
AB  - A method was developed for preparing N-hydroxysuccinimide (NHS)-activated silica
      for use in immobilizing human serum albumin (HSA) within HPLC columns. This
      support was made by reacting aminopropyl silica with disuccinimidyl suberate
      (DSS). Solid state 13C NMR was used to examine the steps in this synthesis. The
      number of NHS groups on the silica's surface was controlled by varying the amount
      of DSS or density of surface amine groups used in the preparing this material.
      Items considered in the use of this material for the immobilization of HSA
      included the amount of protein added to the support, the reaction time, and the
      pH of the coupling buffer. These supports were then evaluated in terms of their
      ability to perform chiral separations for R/S-warfarin and D/L-tryptophan.
      Advantages of this method compared to current immobilization techniques for HSA
      included its better long-term stability and the fact that it did not require the
      use of any reducing agents. The approaches developed in this work are not limited
      to HSA but can be used with other proteins or amine-containing ligands.

PMID- 15499918
TI  - Influence of inorganic mobile phase additives on the retention, efficiency and
      peak symmetry of protonated basic compounds in reversed-phase liquid
      chromatography.
AB  - Inorganic eluent additives affect the retention of protonated basic analytes in
      reversed-phase HPLC. This influence is attributed to the disruption of the
      analyte solvation-desolvation equilibria in the mobile phase, also known as
      "chaotropic effect". With an increase of counteranion concentration analyte
      retention increases with concomitant decrease in the tailing factor. Different
      inorganic counteranions at equimolar concentrations affect protonated basic
      analyte retention and peak symmetry to varying degrees. The effect of the
      concentrations of four different inorganic mobile phase additives (KPF6, NaClO4,
      NaBF4, NaH2PO4) on the analyte retention, peak symmetry, and efficiency on a C8
      bonded silica column has been studied. The analytes used in this study included
      phenols, toluene, benzyl amines, beta-blockers and ophthalmic drugs. The
      following trend in increase of basic analyte retention factor and decrease of
      tailing factor was found: PF6- > ClO4- approximately BF4- > H2PO4-. With the
      increase of the counteranion concentration greater analyte loading could be
      achieved and consequently an increase in the apparent efficiency was observed
      until the maximum plate number for the column was achieved. At the highest
      concentration of counteranions, the peak efficiency for most of the basic
      compounds studied was similar to that of the neutral markers. In contrast, the
      neutral markers, such as phenols, showed no significant changes in retention,
      efficiency or loading capacity as counteranion concentration was increased.

PMID- 15499919
TI  - Rapid method development for chiral separation in drug discovery using multi
      column parallel screening and circular dichroism signal pooling.
AB  - A novel strategy for rapid chiral method development has been developed using
      multi-column parallel screening and circular dichroism (CD) signal pooling.
      Described is the first use of a customized HPLC system that integrates an HPLC
      auto-sampler, one pump and five divided channels with five columns and five UV
      detectors to screen five chiral stationary phases (CSPs) simultaneously in
      parallel. A high-pressure semi-prep on-line pre-filter, a six-port manifold and
      five individually adjusted backpressure restrictors were installed in the system
      which allowed the sample and mobile phase to be evenly distributed over the five
      columns and UV detectors. The five CSPs, namely Chiralpak AD and AS, Chiralcel OJ
      and OD and Whelk-O1, were screened. The system guarantees a five-fold increase in
      speed for chiral column scouting compared with the widely used automated
      sequential column switching approach, and does not have the limitations of the
      coupled column screening approach for enantiomers whose elution order could be
      reversed on CSPs. Furthermore, the five channels after the UV detectors were
      recombined using a reversed flow splitter into a CD detector. The pooled CD
      signal from the five channels was recorded to track the elution order of the
      resolved enantiomers and to determine their sign, positive or negative. The
      signal pooling allows for the effective use of a single CD detector for multiple
      columns since unresolved racemate has little CD signal, and observing the sign of
      CD signal for one of the two enantiomer UV peaks is sufficient for tracking the
      enantiomeric elution order.

PMID- 15499920
TI  - Effect of the mobile phase on antibody-based enantiomer separations of amino
      acids in high-performance liquid chromatography.
AB  - The effect of the mobile phase parameters flow rate, temperature, pH and ionic
      strength, as well as the addition of various organic modifiers on the enantiomer
      separation of various aromatic alpha-amino acids was investigated using two
      antibody-based chiral stationary phases that have opposing stereoselectivity. On
      both columns, a decrease in flow rate or temperature resulted in increased
      interaction with the retained enantiomer. It was found that the retention factor
      k2 depends on the affinity between the analyte and the immobilized antibody and
      is not independent of the flow rate. Optimum separations of all amino acids
      investigated were obtained at pH 7.4 on both columns. While increased k2 values
      were obtained at low ionic strength on the anti-D-amino acid antibody column, no
      such effect was observed on the anti-L-amino acid antibody column. The addition
      of organic modifiers did not improve separations. In all studies, the unretained
      enantiomer eluted with the void volume.

PMID- 15499921
TI  - Determination of free molecular phenolics and catechins in wine by solid phase
      extraction on polymeric cartridges and liquid chromatography with diode array
      detection.
AB  - The use of HLB Oasis polymeric cartridges to extract phenolic acids and aldehydes
      from red wines has been assayed and compared with the combination of ODS and SAX
      cartridges. The recoveries on the polymeric cartridges resulted to be notably
      higher with good precisions. The best operation conditions (cartridge
      conditioning, sample volume, clean-up and elution) for these latter were selected
      by experiments carried out on a synthetic wine sample spiked with 14 compounds
      and on red wine samples. A matrix-matched calibration was advisable to reduce the
      influence of the matrix in the quantification of the analytes as it was verified
      from the application of standard addition calibrations on several wine samples.
      Determination of the analytes in the extracts was performed by reversed-phase
      HPLC using mobile-phase and flow gradients and detection at 250, 280 and 340 nm.

PMID- 15499922
TI  - Application of high-performance liquid chromatography-tandem mass spectrometry to
      the identification of biologically active peptides produced by milk fermentation
      and simulated gastrointestinal digestion.
AB  - Identification of biologically active peptides in food matrices is a challenging
      task in food technology. In the present study, we propose a strategy for the
      rapid identification of peptides in complex food fractions and targeting of
      potentially bioactive peptides according to previous studies of activity
      structure relationship. A large number of peptides included in the Mr 3000
      permeate of a fermented product and its hydrolysate (obtained by simulated
      gastrointestinal digestion) could be easily identified using HPLC coupled on line
      to an ion trap mass spectrometer. Three of the identified sequences have
      previously been described as angiotensin-converting enzyme (ACE) inhibitors. The
      sequence of some peptides allowed us to anticipate the presence of ACE-inhibitory
      activity and several peptides were selected to initiate studies on
      antihypertensive, antioxidant and cytomodulatory activity.

PMID- 15499923
TI  - Characterisation by high-performance liquid chromatography-multiple mass
      spectrometry of intermediate compounds formed from mepanipyrim photoinduced
      degradation.
AB  - Mepanipyrim, a widely used pyrimidinic fungicide, has been photocatalytically
      degraded in aqueous solution on TiO2. The purpose of this study is to
      artificially produce degradation compounds similar to those formed in the
      environment. Numerous intermediates have been identified and characterised
      through a MSn spectra analysis, allowing us to give insight into the early steps
      of the degradation process. Several concomitant pathways occur concerning both
      reductive and/or oxidative attacks; the main steps involve the cleavage of triple
      bond, mono and bihydroxylation of the parent molecule, loss of benzene moiety
      and/or propynylic chain. All these structures are easily degraded themselves, so
      that the only species recognised to endure in the investigated times is
      guanidine. A mechanism of transformation accounting for the identified
      intermediates is proposed.

PMID- 15499924
TI  - Determination of sixteen UV filters in suncare formulations by high-performance
      liquid chromatography.
AB  - Reversed-phase liquid chromatography (RP-LC) with UV detection was developed for
      the simultaneous determination of 16 organic UV filters worldwide authorized in
      suncare products. The filters determined were: 4-aminobenzoic acid, homosalate,
      benzophenone-3,2-phenylbenzimidazole-5-sulfonic acid, terephthalidene dicamphor
      sulfonic acid, 4-tert-butyl-4'-methoxy-dibenzoylmethane, octocrylene, 2
      ethylhexyl-4-methoxycinnamate, isoamyl-p-methoxycinnamate, ethylhexyltriazone,
      drometrizole trisiloxane, diethylhexyl butamido triazone, 3-(4-methylbenzyliden)
      camphor, 2-ethylhexylsalicylate, 2-ethylhexyl-4-dimethylaminobenzoate and
      benzophenone-4. A C18 stationary phase and a gradient of ethanol-aqueous acetate
      buffer containing 0.2 mM of EDTA, was used with a flow-rate of 1.0 ml/min. UV
      detection was carried out at 313 and 360 nm. The analysis required 32 min and the
      limits of detection were between 30 and 4130 mg/kg in the original suncare
      product. Tween 80 was used to break down the different emulsions in order to
      procure a proper extraction of the UV filters. The method was validated for UV
      filters in three matrices, oil, water-in-oil emulsion and oil-in-water emulsion.
      Recoveries from spiked samples were 86-113% depending on the matrix used.

PMID- 15499925
TI  - Rice starch granule characterization by flow cytometry scattering techniques
      hyphenated with sedimentation field-flow fractionation.
AB  - Sedimentation field-flow fractionation (SdFFF) elution mode of micron sized
      particle is described generically as "Hyperlayer" and involves particle size,
      density, shape and rigidity. It requires the use of specific detectors of mass,
      size, surface, or of other characteristics of the eluted particles. Correlation
      of FFF retention data with such signals gives hyphenated information about
      particle properties. Flow cytometry (FC) is a multi dimensional particle counter,
      which permits specific particle property characterization using light scattering
      and fluorescence principles. It appears therefore as a powerful technique for
      micron sized species description. FC is mostly known for cell analyses, while its
      potential is much broader once proper calibration performed. In this report,
      forward angle signal (FS) is calibrated in size by using standard latex beads and
      produces, for a given particle sample, a number versus size histogram, describing
      particle size distribution. These histograms can be an alternative to Coulter
      counting. That methodology is tested with rice starch population (RSP) fractions
      obtained from FFF separation.

PMID- 15499926
TI  - Adsorption characterisation of different volatile organic compounds over alumina,
      zeolites and activated carbon using inverse gas chromatography.
AB  - Adsorption parameters (enthalpy of adsorption, free energy of adsorption) of
      several alkanes, cyclic hydrocarbons, aromatic hydrocarbons and chlorinated
      compounds on different adsorbents (alumina, zeolites 13X and 5 A, and activated
      carbon) were determined by inverse gas chromatography. Dispersive surface energy
      interaction and specific interaction parameters were determined for each solute
      adsorbent system. It was found that mesoporous alumina presents lower enthalpy of
      adsorption than the microporous materials. Furthermore, zeolite 13X, which has
      wider pores than zeolite 5 A, exhibits a higher adsorption capacity.

PMID- 15499927
TI  - Analysis of anisoles in wines using pervaporation coupled to gas chromatography
      mass spectrometry.
AB  - Two procedures for the determination of 2,4,6-trichloroanisole, 2,6
      dichloroanisole and 2,4,6-tribromoanisole in tainted wines have been developed.
      Both methods are based on pervaporation (PV) of the analytes and final
      determination by gas chromatography-ion-trap tandem mass spectrometry (GC-MS). In
      the Approach A, pervaporation was directly coupled to the GC-MS system (PV-GC
      MS/MS) and in Approach B a solid-phase cryogenic trap-thermal desorption (CT-TD)
      device was connected to the pervaporator (PV-CT-TD-GC-MS/MS). Results show that
      last coupling present better sensitivity as well as precision. Detection limits
      (DLs) for 2,4,6-trichloroanisole were estimated to be 25.8 and 4.2 ng l(-1) for
      Approaches A and B, respectively, when 10 ml of sample was analysed. Linear range
      of the calibration curves ranged from quantification limit to 15 ng for PV-GC
      MS/MS and from quantification limit to 2 ng for PV-CT-TD-GC-MS/MS. Due to the low
      threshold odour concentration of these compounds in wine, Approach B is proposed
      as a reliable method for analytical quality control of this product.

PMID- 15499928
TI  - Determination of organochlorine pesticide residues in honey from the central zone
      of Portugal and the Valencian community of Spain.
AB  - In this study nine organochlorine pesticide residues (alpha-, beta-, and gamma
      hexachlorocyclohexane (HCH), hexachlorobenzene (HCB), aldrin, p,p'-DDE, p,p'-DDD,
      o,p'-DDT, and p,p'-DDT) in forty nine samples of honey collected from markets of
      Portugal and Spain during 2001 and 2002, respectively, were evaluated. For this
      evaluation, three analytical procedures were studied. The analytical procedure,
      based on LLE extraction with ethyl acetate followed by gas chromatography
      electron-capture detection (GC-ECD) for quantification, and mass spectrometry (GC
      MS) for confirmation, has been selected. Recoveries of spiked samples ranged from
      68%, for beta-HCH, and 126% for p,p'-DDT, for fortification levels between 10 and
      100 microg/kg, and 64%, for alpha-HCH, and 143% for gamma-HCH for fortification
      levels between 20 and 200 microg/kg. Limits of quantification, using GC-ECD, were
      from 0.01 and 0.10mg/kg, and limits of detection between 0.001 and 0.02 mg/kg.
      Fourteen Valencian samples were contaminated, containing residues of HCB or/and
      HCH isomers. The frequency of detection was 56% for Spanish samples. In Portugal,
      23 samples were contaminated, what means 95.8%. In Spanish samples,
      concentrations range from nd to 0.03 mg/kg for HCB, and nd to 2.24 mg/kg for HCH
      total. The mean concentration and standard deviation were 0.017+/-0.011 mg/kg for
      HCB, and 0.579+/-0.747 mg/kg for HCH-total, contributing the gamma isomer with
      the highest values. The samples from Portugal showed higher levels. Levels of HCB
      ranged from nd to 0.39 mg/kg. HCH-total ranged from nd to 4.86 mg/kg, and DDT
      total from nd to 0.658 mg/kg. Mean concentration and standard deviation were
      0.09+/-0.116 mg/kg for HCB, 1.357+/-1.30 mg/kg for HCH-total, and 0.143+/-0.193
      mg/kg for DDT-total.

PMID- 15499929
TI  - Characterization of Co, Fe and Mn-exchanged zeolites by inverse gas
      chromatography.
AB  - The adsorption of several alkanes, cyclic hydrocarbons, aromatic hydrocarbons and
      chlorinated compounds on NaX, CaA, and exchanged Co, Mn and Fe zeolites as
      adsorbents was investigated. Zeolite composition and structure was determined by
      ICP-mass spectroscopy, XRD, and nitrogen adsorption. Adsorption parameters
      (enthalpy of adsorption and free energy of adsorption) as well as dispersive
      surface energy interaction and specific interaction parameters were determined
      for each solute-adsorbent system by inverse gas chromatography (IGC). The
      original zeolites NaX and CaA show the higher values of enthalpy of adsorption
      but specific interactions depend on the metal exchanged. Zeolites Mn-NaX and Co
      NaX exhibit the strongest interactions with benzene, whereas zeolite Co-CaA shows
      the strongest interactions with chlorinated compounds. The trivalent cation
      (Fe3+) does not affect the either the adsorption efficiency or specific
      interaction.

PMID- 15499930
TI  - Separation of basic compounds by capillary electrochromatography on an X-Terra
      RP18 stationary phase.
AB  - In this work we demonstrate that the X-Terra RP18 stationary phase, specially
      designed for the analysis of basic compounds in liquid chromatography, may be
      successfully used in capillary electrochromatography. Although this packing
      material does not afford a sufficient electroosmotic flow with classical hydro
      organic mobile phases, the addition of a surfactant that adsorbs onto the
      stationary phase allows to generate a sustainable electroosmosis flow (EOF), the
      direction of which depends on the charge of the surfactant. The way of
      manipulating the electroosmotic flow is described (nature and concentration of
      the added surfactant, proportion of the organic modifier in the mobile phase,
      pH). It is then demonstrated that high efficiencies can be reached with this
      packing material (up to 220,000 plates/m with a mean diameter particles of 3.5
      microm) when it is operated at high linear velocities. Then the separations of
      different classes of compounds such as amphenicol antibiotics, macrolide
      antibiotics or basic test solutes with mobile phases with pH up to 10.8 are
      described. The influence of the addition of sodium dodcylsulfate (SDS) to the
      mobile phase on the retention is described and the selectivity of the X-Terra
      RP18 stationary phase is compared to that of a more traditional phase, i.e.
      Hypersil C18 stationary phase with SDS added to the mobile phase. However, it is
      shown that a good repeatability of the retention factors can only be obtained
      when the ionization of the compounds is totally suppressed since electrolysis of
      the buffered hydro-organic mobile phase occurs in the buffer reservoirs leading
      to a variation of the mobile phase pH and consequently to a modification of the
      ionization degree of the solutes having their pKa close to the mobile phase pH.

PMID- 15499931
TI  - Generic, highly selective and robust capillary electrophoresis method for
      separation of a racemic mixture of glitazone compounds.
AB  - A generic, highly selective, and robust capillary electrophoresis (CE) method was
      developed for separation of a racemic mixture of three available glitazone
      compounds (also known as thiazolidinediones) in active pharmaceutical ingredients
      (API) and tablets. The method separated the R and S enantiomers of balaglitazone,
      pioglitazone and rosiglitazone, and showed that the samples contained an equal
      (50:50) quantity of the enantiomers as a mixture. After a simple extraction of
      samples with acetonitrile:water (80:20), separation was performed using a
      combination of two cyclodextrins: sulfobuthylether-beta-cyclodextrin (SB-beta-CD)
      and dimethyl-beta-cyclodextrin (DM-beta-CD) in the electrolyte at pH 8.0. The
      method showed a very good specificity, and all separations were achieved with a
      resolution (Rs) over 3.0. The developed CE method was then validated. The Rs for
      the separations were 3.5 for balaglitazone enantiomers, 3.5 for pioglitazone
      enantiomers, and 3.7 for rosiglitazone. The squared correlation coefficients (r2)
      were found to be 0.999 for all three compounds. The range of the CE method
      (injection volume was approximately 4 nl) was demonstrated to be from 1.0 to 2.4
      ng. The R.S.D. in the repeatability study was found to be less than 0.5 for
      area/area ratio (and 3.0% for area) for all three compounds. The R.S.D. in the
      intermediate precision study was found to be less than 0.7 for area/area ratio
      (and 4.5% for area) for all three compounds. Generally, the method showed good
      robustness. Resolution between the enantiomers peak was maintained acceptable
      throughout the small variations around the pH value of the buffer, different
      capillary, CE instrument and electrolytes ion strength capacity, but changes in
      concentration of cyclodextrins and acetonitrile showed significant effects on
      separations and affected the resolution. The validation results showed that the
      CE method was suitable for separation of the racemic mixtures of the three
      glitazone drugs. The CE method was then applied for routine test during the drug
      and formulation development work of balaglitazone. Due to the achieved results
      from this work, it is the authors' belief that this method can easily separate
      other glitazone racemic mixtures.

PMID- 15499932
TI  - Microchip capillary electrophoresis with amperometric detection for rapid
      separation and detection of phenolic acids.
AB  - A microchip capillary-electrophoresis protocol for rapid and effective
      measurements of food-related phenolic acids (including chlorogenic, gentisic,
      ferulic, and vanillic acids) is described. Relevant parameters of the chip
      separation and amperometric detection are examined and optimized. Under optimum
      conditions, the analytes could be separated and detected in a 15 mM borate buffer
      (pH 9.5, with 10% of methanol) within 300 s using a separation voltage of 2000 V
      and a detection voltage of +1.0 V. Linear calibration plots are observed for
      micromolar concentrations of the phenolic acid compounds. The negligible sample
      volumes used in the microchip procedure obviates surface fouling common to
      amperometric measurements of phenolic compounds. The new microchip protocol
      offers great promise for a wide range of food applications requiring fast
      measurements and negligible sample consumption. An application on a commercial
      red wine was performed with minimal sample preparation and promising results.

PMID- 15499933
TI  - Chiral capillary electrophoretic method for quantification of apomorphine.
AB  - A new method for chiral determination of apomorphine enantiomers was developed
      and validated. Seven different neutral and charged cyclodextrins were tested for
      enantioselectivity on R,S-apomorphine. Sulfobutylether-beta-cyclodextrin was
      found to offer the best resolution, but with this system, four peaks were
      detected from a solution of the two enantiomers, which was suggested to be the
      result of different forms of the complex between the selector and apomorphine. A
      complexation constant was estimated for a complex of 1:1 ratio for the second and
      the fourth peak, whereas the other two peaks were fitted to a model ratio of 1:2
      (analyte-selector). To avoid this phenomenon, hydroxypropyl-beta-cyclodextrin was
      then chosen as the chiral selector. An optimisation study was performed on three
      factors: concentration of the chiral selector, pH of the buffer, and applied
      voltage. Optimum conditions were: 14 mM of hydroxypropyl-beta-cyclodextrin, pH
      3.0, and 16 kV. UV detection was at 200 nm. The method was validated at the
      chosen conditions, offering a limit of detection of 0.2 microM and a limit of
      quantification of 0.5 microM. The validated method was applied for the
      determination of R,S-apomorphine in a transport study with an in vitro cell
      culture model of the intestinal mucosa (Caco-2).

PMID- 15499934
TI  - Rapid protein separations in ultra-short microchannels: microchip sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis and isoelectric focusing.
AB  - We have developed novel protein gel electrophoresis techniques, sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and isoelectric focusing
      (IEF) in short microchannels (approximately millimeters) that take less than a
      minute. A photopatterning technique was used to cast in situ crosslinked
      polyacrylamide gel in a microchannel to perform SDS-PAGE. A fluorescent protein
      marker sample (Mr range of 20,000-200,000) was separated in less than 30 s in
      less than 2 mm of channel length. Crosslinked polyacrylamide gel, patterned in
      channels using UV light, provides higher sieving power and sample stacking
      effect, therefore yielding faster and higher-resolution separation in a chip. IEF
      of proteins was also achieved in a microchannel, and several proteins were
      focussed within tens of seconds in mm-length channels. As resolution in IEF is
      independent of separation distance, focusing in ultra-short channels results in
      not only faster separation but also more concentrated bands potentially allowing
      detection of low-concentration species.

PMID- 15499935
TI  - Rapid determination of aristolochic acid I and II in Aristolochia plants from
      different regions by beta-cyclodextrin-modified capillary zone electrophoresis.
AB  - Chinese herbs nephropathy (CHN) is a kind of severe kidney disease caused by
      excessively taking aristolochic acid (AA). Hence, it is essential for health
      security and quality control of related herbal medicines to develop an efficient
      method for separation and determination of these two important components in
      Traditional Chinese Medicines. In this study, a rapid capillary zone
      electrophoresis (CZE) method using 120 mM sodium borate buffer containing 10 mM
      beta-cyclodextrin (beta-CD) as modifier was firstly developed for the analysis of
      AA-I and AA-II within 4min in some medicinal plant samples. The separation
      conditions including pH of running buffer, CD content in the buffer system,
      applied voltage and capillary temperature were systematically optimized, and two
      kinds of aristolochic acids in 37 herbal samples of Aristolochia plants were
      successfully determined with high separation efficiency, satisfactory
      sensitivity, repeatability and recovery. The result indicated high variability in
      the contents of aristolochic acids due to different species and regions. The
      comparison of CZE method with high performance liquid chromatography (HPLC) was
      also discussed.

PMID- 15499936
TI  - Separation of flavonoids from the seeds of Vernonia anthelmintica Willd by high
      speed counter-current chromatography.
AB  - Several flavonoids including 2',3,4,4'-tetrahydroxychalcone, 5,6,7,4'
      tetrahydroxyflavone and butin, were separated from the seeds of Vernonia
      anthelmintica Willd by high-speed counter-current chromatography using a two-step
      operation. Two different types of solvent systems were used: chloroform
      dichloromethane-methanol-water (2:2:3:2, v/v) and 1,2 dichloroethane-methanol
      acetonitrile-water (4:1.1:0.25:2, v/v). From 1 kg of seeds of Vernonia
      anthelmintica Willd the method yielded about 45 mg of 2',3,4,4'
      tetrahydroxychalcone, 40mg of 5,6,7,4'-tetrahydroxyflavone, and 55 mg of butin.
      Each isolated component showed 95-97% purity as determined by high-performance
      liquid chromatography analysis. These purified compounds were characterized by MS
      and NMR.

PMID- 15499937
TI  - Thermodynamic study on the gas chromatographic separation of the enantiomers of
      aromatic alcohols using heptakis(2,3-di-O-methyl-6-O-tert-butyldimethylsilyl)
      beta-cyclodextrin as a stationary phase.
AB  - Gas chromatographic separation of the enantiomers of nineteen structurally
      related aromatic alcohols was investigated as a function of temperature using a
      heptakis(2,3-di-O-methyl-6-O-tert-butyldimethylsilyl)-beta-cyclodextrin-coated
      capillary column. Thermodynamic parameters were determined and compared with
      those obtained with the nonchiral, reference stationary phase, OV-1701. While the
      -deltaH and -deltaS values for the more retained enantiomers of all nineteen
      alcohols are comparable on the chiral stationary phase used, the -delta(deltaH)
      and -delta(deltaS) values are considerably different. Of all the solutes tested,
      enantiodiscrimination was the greatest for the 2,6-difluoro-alpha-methylbenzyl
      alcohol.

PMID- 15499938
TI  - Combination of gas chromatography-mass spectrometry and mass spectral
      deconvolution for structural elucidation of an unusual C29-steroid detected in a
      complex sedimentary matrix.
AB  - A complex sedimentary sample from the Monterey Formation (CA, USA) has been
      submitted to GC-MS analysis followed by mass spectral deconvolution using
      Automated Mass Spectral Deconvolution and Identification System (AMDIS).
      Adjusting the parameters of the software allowed for the extraction of the
      spectrum of an unusual steroidal hydrocarbon coeluting with the major compound of
      the chromatogram. Following a careful interpretation of the "extracted" mass
      spectrum, the structure of the unknown has been postulated to be the 4,14
      dimethylcholestane (DMC). Possible origins of this rare steroid are briefly
      discussed. Thus, application of AMDIS appears to be particularly suitable for the
      GC-MS analysis of natural complex mixtures characterized by a high number of
      analytes present in low amounts.

PMID- 15499939
TI  - Thin-layer chromatographic behavior and separation of alkaline earth metals on
      silica gel in aqueous sodium perchlorate solution.
AB  - The thin-layer chromatographic behavior of alkaline earth metal ions (Mg2+, Ca2+,
      Sr2+, and Ba2+) in aqueous sodium perchlorate solutions on silica gel thin-layers
      impregnated with sodium hydroxide has been surveyed as a function of salt
      concentration. At salt concentrations above 2 mol 1(-1), the selectivity of the
      metals increased with a decrease in the crystal ionic radii; with further
      increases in salt concentration, the selectivity differences among the metals
      expanded remarkably. In the present systems, it was supposed that the cation
      exchange, the surface complexation, and the salting-out effect participate
      simultaneously in the adsorption of the metals on silica gel. Typical
      chromatograms for the mutual separation of the alkaline earth metals are
      presented.

PMID- 15499941
TI  - Defective assembly of the respiratory chain.
AB  - A functional respiratory chain is dependent on protein components encoded by both
      mtDNA and nuclear DNA. Isolated cytochrome c oxidase (COX) deficiency is often
      caused by mutations in nuclear genes regulating the assembly of the 13 protein
      subunits of this complex. The accompanying paper by Zeman and co-workers reports
      that mutations in SCO2 are common in infantile COX deficiency and are associated
      with a very poor prognosis. CONCLUSION: Molecular diagnosis is often feasible in
      patients with COX deficiency and particular attention should be paid to mutations
      in COX assembly genes.

PMID- 15499940
TI  - Determination of phosphoamino acids derivatized with 5-(4,6-dichloro-s-triazin-2
      ylamino)fluorescein by micellar electrokinetic chromatography.
AB  - A sensitive analytical protocol for determining phosphoamino acids using
      capillary electrophoresis coupled with laser-induced fluorescence detection has
      been developed. The technique involved the derivatization of the phosphoamino
      acids with fluorescent reagent 5-(4,6-dichloro-s-triazin-2-ylamino)fluorescein
      (DTAF) and the analyses of the derivatives by micellar electrokinetic
      chromatography with laser induced fluorescence detection (MEKC-LIF). Different
      variables that affect derivatization (DTAF concentration, pH, temperature and
      time) and separation (kind of surfactant, pH and concentration of buffer) were
      studied. The baseline separation of three phosphoamino acids could be obtained in
      less than 11 min with good reproducibility. There was a linear relationship
      between the peak area of the analyte and its concentration, with correlation
      coefficients in the range of 0.9979-0.9997. The concentration detection limits
      (signal to noise = 3) with respect to each single phosphoamino acid were in the
      range of 0.5-1 nM. The developed method was successfully applied for the
      determination of phosphoamino acids in the hydrolyzed phosphorylated protein
      samples.

PMID- 15499942
TI  - Rehospitalization of very preterm infants.
AB  - Rehospitalization rates of very preterm infants because of reasons that are
      related to neonatal morbidity states can be decreased with further improvement of
      neonatal intensive care provided. CONCLUSION: Analysis of rehospitalization data
      should be included in follow-up programmes as a contribution to the development
      of strategies to improve neonatal care and the ultimate outcome for very-low
      birthweight infants.

PMID- 15499943
TI  - The Nils Rosen von Rosenstein Award 2004.

PMID- 15499944
TI  - Perinatal health in Pakistan: a review of the current situation.
AB  - The perinatal mortality rate of 63-92/1000 births as reported from two provinces
      of Pakistan is unacceptably high. A vast majority of births and neonatal deaths
      occur at home and remain unregistered. In spite of a number of child survival
      programmes of proven efficacy in place, the impact on perinatal health is poor.
      CONCLUSION: Initiatives such as behaviour change communication, skill-based
      training of birth attendants and reaching the un-reached may be the key future
      strategies to reduce perinatal losses.

PMID- 15499945
TI  - Breastfeeding, very long polyunsaturated fatty acids (PUFA) and IQ at 6 1/2 years
      of age.
AB  - AIM: Breastfeeding seems to be favorable for cognitive development. Could levels
      of polyunsaturated fatty acids (PUFA) explain this? METHODS: Pregnant mothers
      were recruited consecutively at maternity care centres. PUFA were analysed in
      colostrum and breast milk at 1 and 3 mo. The product-precursor ratios of n-6+n-3
      PUFA were examined as measures of activity in respective steps in the fatty acid
      metabolic chain. Also, the quotient between DHA and AA was analysed. The children
      were tested with the full WISC-III at 6.5 y. RESULTS: First, the influence of
      length of breastfeeding was analysed by multiple regression together with
      relevant cofactors (except for PUFA). In the best models, 46% of the variation in
      total IQ was explained. Length of breastfeeding contributed significantly to
      total IQ (beta = 0.228, p = 0.021), verbal IQ (beta = 0.204, p = 0.040) and
      performance IQ (beta = 0.210, p = 0.056). There were no significant single
      correlations between PUFA and measures of cognitive development. However, in
      multiple regression analysis of colostrum, significant beta-coefficients were
      found for steps 4+5 in the fatty acid metabolic chain (beta = 0.559, p = 0.002).
      If length of breastfeeding and gestation week were added to steps 4+5, this three
      factor model could explain 67% of the variation of total IQ. Introducing length
      of breastfeeding and gestation week together with the quotient DHA/AA (beta =
      0.510, p < 0.001) yielded a three-factor model, which explained 76% of the
      variation in total IQ. CONCLUSION: Our findings could be interpreted as
      supporting the importance of high levels of PUFA for cognitive development.
      However, the sample is small and the results must be interpreted with caution.

PMID- 15499946
TI  - Effect of activators and the phosphodiesterase inhibitors pentoxifylline and
      enoximone on the deformability of neutrophils in neonates and adults.
AB  - BACKGROUND: Stimulated polymorphonuclear leukocytes (PMN) are extremely rigid
      compared to resting PMN. They may obstruct narrow vessels and contribute to
      ischaemic organ injury. Deformability is a prerequisite for both active and
      passive movement in the microcirculation. AIM: The investigation was designed to
      study whether stimulators and inhibitors of stimulation show different effects on
      deformability of neonatal and adult PMN. METHODS: Deformability of PMN was
      assessed by complete aspiration of a PMN into a micropipette with an internal
      diameter of 5 microm. Blood samples from 20 neonates and 20 adults were studied
      before and after stimulation with N-formyl-methionyl-leucyl-phenylalanine (fMLP),
      interleukin-8 (IL-8) or tumour necrosis factor-alpha (TNF-alpha). Moreover,
      effects of the phosphodiesterase inhibitors Pentoxifylline (PTX) and Enoximone on
      the deformability of stimulated PMN were investigated. RESULTS: fMLP, IL-8 and
      TNF-alpha significantly delayed aspiration times of PMN in relation to the
      concentrations of the stimulators. The addition of PTX or Enoximone to stimulated
      PMN increased the deformability up to 60% depending on the concentration of the
      inhibitors. No significant differences in the aspiration times were found between
      neonatal and adult PMN at any of the experimental conditions after activation
      with the three stimulators and treatment with the two inhibitors. CONCLUSION:
      Neonatal and adult PMN show similar reduction of passive deformability when
      stimulated with either fMLP, IL-8 or TNF-alpha compared to resting PMN and a
      similar improvement of deformability in response to PTX or Enoximone.

PMID- 15499947
TI  - Pulmonary outcome in adolescents of extreme preterm birth: a regional cohort
      study.
AB  - AIMS: The pulmonary outcome of extreme prematurity remains to be established in
      adults. We determined respiratory health and lung function status in a population
      based, complete cohort of young preterms approaching adulthood. METHODS: Forty
      six preterms with gestational age < or = 28 wk or birthweight < or = 1000 g, born
      between 1982 and 1985, were compared to the temporally nearest term-born subject
      of equal gender. Spirometry, plethysmography, reversibility test to salbutamol
      and methacholine bronchial provocation test were performed. Neonatal data were
      obtained from hospital records and current symptoms from validated
      questionnaires. RESULTS: When entering the study at a mean age of 17.7 (SD: 1.2)
      y, a doctor's diagnosis of asthma and use of asthma inhalers were significantly
      more prevalent among preterms than controls (one asthmatic control compared to
      nine preterms, all but one using asthma inhalers). Peak expiratory flow (PEF) and
      forced expiratory volume in 1 s (FEV1) were decreased and the discrepancies
      relative to controls increased parallel to increased severity of neonatal lung
      disease. Parameters of increased neonatal oxygen exposure significantly predicted
      FEV1. Adjusted for height, gender and age, FEV1 was reduced by a mean of 580 ml/s
      in subjects with a history of bronchopulmonary dysplasia. Fifty-six percent of
      preterms had a positive methacholine provocation test compared to 26% of
      controls. CONCLUSION: A substantially decreased FEV1, increased bronchial
      hyperresponsiveness and a number of established risk factors for steeper age
      related decline in lung function were observed in preterms. A potential for early
      onset chronic obstructive pulmonary disease is present in subsets of this group.

PMID- 15499948
TI  - Contributions of bone maturation measurements to the differential diagnosis of
      neonatal transient hypothyroidism versus dyshormonogenetic congenital
      hypothyroidism.
AB  - AIM: To a) evaluate the contribution of bone maturation in the diagnosis of
      neonatal transient hypothyroidism versus dyshormonogenetic congenital
      hypothyroidism in full-term newborns, and b) use bone maturation to test the
      hypothesis that neonatal transient hypothyroidism is perinatal in onset.
      MATERIALS AND METHODS: The study included 20 patients with dyshormonogenetic and
      43 with transient hypothyroidism. Thyroid function and measurements of the distal
      femoral epiphysis area, obtained at the time of first confirmatory diagnosis,
      were compared between the two groups. The epiphysis area in two control groups
      with normal thyroid function was also measured and compared with that in patients
      with transient hypothyroidism, at age 1-3 d (control A), or at the age when
      normal thyroid function was confirmed (control B). RESULTS: Mean epiphysis area
      was 0.04 cm2 in patients with dyshormonogenetic versus 0.22 cm2 in patients with
      transient hypothyroidism (p < 0.0001). An area <0.05 cm2 was limited to patients
      with dyshormonogenetic hypothyroidism. Conversely, a normal area (>0.2 cm2) was
      only observed in patients with transient hypothyroidism. Mean epiphysis areas in
      control A (0.20 cm2) and in patients with transient hypothyroidism were similar
      (p = 0.37), consistent with perinatal onset of transient hypothyroidism. Mean
      epiphysis area in control B (0.31 cm2) was significantly greater than in patients
      with transient hypothyroidism (p < 0.01). CONCLUSIONS: A short duration of
      hypothyroidism can significantly delay bone maturation. Examination of bone
      maturation at initial confirmatory evaluation yields important information
      pertaining to congenital hypothyroidism, not only to predict intellectual
      development, but also to evaluate the risk of dyshormonogenetic hypothyroidism.

PMID- 15499949
TI  - Physical activity as measured by accelerometry in children receiving growth
      hormone.
AB  - AIM: Parents of children treated with growth hormone (GH) frequently report to
      the paediatrician that their children have become more physically active. In the
      present study, activity patterns of GH-treated children were measured and
      compared to those of healthy controls. METHODS: Subjects were 25 children at the
      start of GH treatment (age 8.4 +/- 2.6 y) and 19 age- and gender-matched controls
      (age 8.8 +/- 3.2 y). Physical activity was assessed with a tri-axial
      accelerometer for movement registration over two separate 2-wk intervals, one
      before the start of GH treatment and one 2 wk after the start of treatment. GH
      treated subjects were categorized as poor responders (change in height over 1 y
      <0.7 SDS, n = 15) or good responders (change in height over 1 y >0.7 SDS, n =
      10). RESULTS: Before therapy, good responders showed a significantly lower
      physical activity compared to healthy controls, spending significantly less time
      on high-intensity activities. This difference disappeared 2 wk after the start of
      therapy. Physical activity in poor responders was not significantly different
      from controls before and after 2 wk of GH therapy. CONCLUSION: Children who
      respond well to GH therapy (change in height >0.7 SDS) showed a reduced amount of
      physical activity before therapy, which was normalized after 2 wk of GH therapy.

PMID- 15499950
TI  - Clinical, biochemical and molecular analyses of six patients with isolated
      cytochrome c oxidase deficiency due to mutations in the SCO2 gene.
AB  - BACKGROUND AND AIM: Cytochrome c oxidase (COX) deficiency represents a
      heterogeneous group of disorders. Numerous proteins are required for efficient
      COX assembly and maintenance. In 26 children with isolated COX deficiency, we
      studied mutations in the SCO2 gene, which is involved in the copper transport
      into the inner mitochondrial membrane, and we analysed the clinical and
      biochemical consequences of SCO2 mutations. METHODS: The activities of
      respiratory chain complexes were measured spectrophotometrically in isolated
      mitochondria and/or crude cell extracts in all available tissues. Two-dimensional
      polyacrylamide electrophoresis (2D-PAGE) was used to separate the complexes and
      their subunits. The mutations were detected by sequencing and RFLP analysis.
      RESULTS: Mutations in the SCO2 gene were found in six children. Early neonatal
      onset of hypertrophic cardiomyopathy and encephalopathy were observed in one boy
      with compound heterozygous mutations C1280T and G1541A. In all five children with
      homozygous mutation G1541A, progressive encephalopathy developed between 2 and 6
      mo of age. Isolated COX deficiency was found in the skeletal muscle, heart, liver
      and brain but not in fibroblasts. 2D-PAGE in the skeletal muscle showed markedly
      decreased amounts of all COX subunits. CONCLUSION: Our results suggest that
      mutations in the SCO2 gene are not rare, at least in our population. Although
      clinical symptoms may rely on the type of SCO2 mutation, the prognosis is
      unfavourable in all patients.

PMID- 15499951
TI  - Antenatal corticosteroids policies in 14 European countries: factors associated
      with multiple courses. The EURAIL survey.
AB  - AIM: To describe antenatal corticosteroids (ANCs) policies in European obstetric
      units and to determine factors that influence the use of multiple courses.
      METHODS: 641 obstetricians from obstetric departments covering a geographical
      area in 14 European countries responded to a questionnaire on ANCs policies.
      Logistic regression was used to identify factors that were related to the use of
      multiple ANCs courses. RESULTS: The survey response rate was 76% (inter-country
      range 33-94%): 11% (0-50%) of the respondents started ANCs from 23 to 24 wk
      gestation, 82% from 24 to 28 wk (50-100%) and 7% from 28 to 36 wk (0-32%). Eighty
      five percent of the units (63-100%) used multiple ANCs courses. After adjustment
      for country, number of infants delivered at 24-32 wk annually in the unit, NICU
      and maternal hypertension, maternal hypertension tended to be an explicative
      factor (OR 1.97; 95% CI: 0.75-5.17). CONCLUSIONS: The high proportion of
      departments that initiated ANCs between 24 and 28 wk of gestation is consistent
      with the high incidence of neonatal morbidity and mortality in that age range.
      Multiple courses are overwhelmingly prescribed in Europe, although their
      risk/benefit ratio compared with a single dose is not yet known. The likelihood
      of using repeated courses of ANCs may be related to the presence of maternal
      hypertension, and this highlights the importance of closely monitoring women at
      risk of premature delivery.

PMID- 15499952
TI  - Birthweight of full-term infants is associated with cord blood CD34+ cell
      concentration.
AB  - AIM: CD34+ cell counts are used to define the haematopoietic stem cell potential
      of a given cord blood transplant. The aim was to test the hypothesis that high
      concentration of cord blood haematopoietic progenitor and stem cells could be a
      reflection of intrauterine growth, of which birthweight is an indicator. METHODS:
      Simple and multiple regression analyses were applied to test cord blood bank data
      on 1368 infants for associations of selected obstetric factors and cellular
      contents of cord blood. RESULTS: When groups were formed based on the extreme
      values (5th versus 95th percentiles) of a given variable, e.g. birthweight, the
      term infants having the highest birthweights were found to have statistically
      significantly higher median cord blood CD34+ cell concentrations. Also, infants
      in the top 50th percentile of relative birthweight had higher median CD34+ cell
      concentration than infants in the low 50th percentile. In multiple regression
      analysis, the correlation between birthweight and CD34+ cell concentration was
      statistically clearly significant. Notably, while an expected correlation between
      gestational age and nucleated cell concentration was found, there was no
      association between infant gestational age and CD34+ cell concentration.
      CONCLUSION: Haematopoietic progenitor and stem cells may reflect intrauterine
      growth and have a more central role in foetal development than has been reported
      earlier.

PMID- 15499953
TI  - Oral hypertonic glucose spray: a practical alternative for analgesia in the
      newborn.
AB  - AIM: Pain and stress have been shown to induce significant physiological and
      behavioural reactions in newborn infants. Pharmacological agents are not
      recommended in neonates for pain relief in minor procedures. Since different
      sweet solutions given orally by syringe have been shown to relieve pain in
      neonates, we decided to compare the analgesic effects of a small dose of glucose
      solution given orally by spray and by syringe during heel lancing in term
      neonates, using a validated behavioural acute pain rating scale. METHODS: Sixty
      hyperbilirubinaemic full-term neonates were studied. We used a randomized,
      masked, placebo-controlled, crossover trial. Each infant was assessed three times
      receiving 0.5 ml 30% glucose in spray form, 0.5 ml 30% glucose by syringe or 0.5
      ml sterile water by syringe in random order, 2 min before heel lancing. RESULTS:
      Pain scores were significantly lower in the 30% glucose given either spray or
      syringe groups compared with the placebo group. No statistically significant
      difference in pain scores was found between the 30% glucose spray group and 30%
      glucose syringe group. CONCLUSIONS: A small dose of 0.5 ml 30% glucose spray has
      an equal analgesic effect to the same dose given by syringe. The spray form has
      the advantage of being easy to use and is well accepted by newborn babies.

PMID- 15499954
TI  - Clinical features and epidemiology of septicaemia and meningitis in neonates due
      to Streptococcus agalactiae in Copenhagen County, Denmark: a 10 year survey from
      1992 to 2001.
AB  - AIM: To elucidate the clinical and biochemical features, and to estimate the
      incidence and outcome of invasive culture-verified group B streptococcal (GBS)
      septicaemia/meningitis in neonates in Denmark. METHODS: Clinical microbiology
      laboratory records in patients 0-3 mo of age were searched for culture-verified
      GBS during 1992-2001 in Copenhagen County. Clinical records at the neonatal
      intensive care unit were reviewed retrospectively. Selected clinical and
      biochemical parameters were evaluated. RESULTS: 61 neonates had culture-verified
      GBS septicaemia/meningitis. The mean annual incidence was 0.76 cases per 1000
      livebirths (range 0.0-1.91). A significant decrease in incidence was observed in
      the latest 3 y. The male:female ratio was 1.3:1. Eighty percent of the neonates
      had early-onset GBS within 24 h, 57% with symptoms at birth. Predominant initial
      symptoms were respiratory (72%), cardiovascular (69%) and neurological (63%).
      Only 4% developed GBS by day 7-90. Seventy-five percent had maternal or neonatal
      risk factors for early-onset GBS disease; 21% had clinical asphyxia, 37% of the
      mothers had premature rupture of membranes and 31% of the mothers were febrile.
      Initial C-reactive protein (CRP) was low, but increased significantly after more
      than 12 h duration of symptoms in 82% of patients. Leucopenia was an important
      initial haematological marker. CONCLUSION: The incidence of early-onset GBS has
      decreased significantly in Denmark, probably because of preventive measures in
      pregnancy and during birth. Respiratory symptoms are early signs of early-onset
      GBS. Initial leucopenia and a late (12-48 h) increase in CRP are valuable markers
      for invasive GBS.

PMID- 15499955
TI  - Re-hospitalization in infants younger than 29 weeks' gestation in the EPIPAGE
      cohort.
AB  - AIM: To estimate the re-hospitalization rate of extremely preterm children during
      infancy and associated factors after the recent improvement in survival rates.
      METHOD: The cohort included all children born before 29 wk of gestation in nine
      French regions in 1997. All admissions between discharge from initial
      hospitalization and 9 mo after birth were considered. Factors studied included
      the child's characteristics at birth and during neonatal hospitalization, risk
      factors for infection after discharge and parents' socio-demographic
      characteristics. Adjusted odds ratios (aOR) for re-hospitalization for all
      reasons and for respiratory disorders were obtained from logistic regression
      models. RESULTS: Of the 376 children, 178 were re-admitted at least once (47.3%;
      95% CI: 42.3-52.4). Fifty-five percent of the hospitalized children were admitted
      at least once for respiratory disorders. The re-hospitalization rate was higher
      for children who had had chronic lung disease (aOR: 2.2; 95% CI: 1.3-3.7), those
      initially discharged between August and October (aOR: 2.5; 95% CI: 1.2-5.1) or
      between November and January (aOR: 3.2; 95% CI: 1.5-6.8), and children living
      with other children under six (aOR: 3.4; 95 %CI: 1.6-7.5). Re-hospitalizations
      were associated with neither gestational age nor the duration of neonatal
      hospitalization. Adjusted odds ratios for re-hospitalization for respiratory
      tract disorders were very similar to those for the overall hospitalizations.
      CONCLUSION: Infants born before 29 wk have a very high risk of re
      hospitalization. The associated factors can help define high-risk groups at
      discharge from the neonatal unit who need special surveillance.

PMID- 15499956
TI  - Breastfeeding and perceived changes in the appearance of the breasts: a
      retrospective study.
AB  - AIM: To investigate the association between breastfeeding and the perception that
      women have of changes in the appearance of their breasts. METHODS: Four hundred
      and ninety-six Italian women were interviewed in three health centres 18 mo (SD
      3.4 mo, range 12.6-23.1 mo) after the birth of their first baby in May 2002.
      Information was collected on pregnancy, infant feeding and bra cup size before
      pregnancy. The main outcome measures were self-reported changes in the appearance
      of the breasts (enlargement or reduction in breast size and loss of firmness) and
      bra cup size at the time of the interview. RESULTS: Seventy-three percent of the
      mothers reported that their breasts were different compared with before
      pregnancy; enlargement and loss of firmness representing the most common changes.
      The prevalence of changes among the mothers who had and had not breastfed was 75%
      and 69%, respectively (relative risk: 1.09, 95% CI: 0.96-1.23). Bra cup size
      before pregnancy was neither associated with the frequency of breastfeeding nor
      with the occurrence of changes in the appearance of the breasts. CONCLUSIONS: In
      Italy, mothers frequently report that the size and the shape of their breasts
      have changed after childbirth, but these changes do not seem to be associated
      with breastfeeding.

PMID- 15499957
TI  - A cohort study of term infants from Vilnius, Lithuania: feeding patterns.
AB  - AIM: To present infant feeding patterns and to relate these to selected
      biological and social factors. METHODS: One hundred and ninety-two infants born
      at four delivery departments were followed prospectively from birth to 12 mo of
      age. Their parents were asked to tick weekly if the infant received items on a
      list of the most common infant foods and drinks, including breast milk. RESULTS:
      All infants started breastfeeding. Median duration of exclusive breastfeeding was
      0.5 mo, and 3.75 mo for "any breastfeeding". Mothers who were older (>25 y),
      better educated (>11 y) and non-smokers breastfed significantly longer (median 4
      mo). Median introduction of cow's milk was 8 (range 2-12) mo. At the age of 12
      mo, 78% of infants received cow's milk and 58% of infants received cow's milk as
      the sole source of milk. Mothers who were younger (<21 y) and less educated (<12
      y) introduced cow's milk significantly earlier. Mean (SD) start of solids was 3.4
      (1.0) mo. Longer duration of breastfeeding was the only factor significantly
      associated with the later start of solids. Ninety-two percent of infants were
      introduced to fresh cheese before 12 mo. Additional liquids were widely given
      both to breastfed and non-breastfed infants. CONCLUSIONS: Compliance with the
      current infant feeding recommendations is not sufficient. Breastfeeding rates are
      low. Use of high-protein products is widespread. More effort should be made to
      educate young, less educated and smoking mothers.

PMID- 15499958
TI  - Clinicians' perspective on quality of life assessment in paediatric clinical
      practice.
AB  - AIM: This study was undertaken to investigate paediatric clinicians' views on and
      use of quality of life (QoL) assessment in clinical practice. METHODS: A survey
      was conducted among members of the Dutch Paediatric Association via e-mail.
      RESULTS: Over half of the 303 respondents (57%) believed that it was possible to
      use QoL questionnaires in clinical practice. The majority indicated that
      assessing QoL was beneficial and that it was especially necessary to assess QoL
      in children with a chronic disease (82%). Although only a minority (17%)
      currently used QoL questionnaires, most respondents would want to use QoL
      questionnaires in the future (76%). Obstacles that prevent the use of QoL
      questionnaires are the extra time needed for assessment, the unavailability of
      standardized questionnaires and insufficient knowledge about QoL. CONCLUSION:
      This survey shows that paediatric clinicians are positive towards QoL assessment,
      but that certain obstacles prevent the use of questionnaires. Thus, to facilitate
      future use, QoL questionnaires need to be developed from the perspective of the
      paediatrician. This means that they need to be developed for clinical use and
      brought to the attention of the paediatric health care community, demonstrating
      their validity to child health care.

PMID- 15499959
TI  - Impulse control, working memory and other executive functions in preterm children
      when starting school.
AB  - AIM: The aim of this study was to explore whether children born preterm have
      deficient executive functions (EF) in comparison with children born at full term,
      and, if so, whether this is dependent on inferior intelligence scores and can be
      correlated to specific neonatal risk factors and gender. METHODS: In a population
      based study, the executive functions of 182 preterm children (birthweight less
      than 1500 g, VLBW) and 125 controls from the Stockholm Neonatal Project were
      assessed at 5 1/2 y with a neuropsychological test battery (Nepsy 1990). RESULTS:
      The controls surpassed the VLBW children on tests of executive functions (EF),
      even after controlling for intelligence (IQ); a necessary correction since there
      were significant correlations between measures of EF and IQ. EF was associated
      with retinopathy of prematurity (ROP), and with visual impairment as a whole. In
      both groups, girls surpassed boys on tests of executive functions. CONCLUSION: We
      conclude that it is possible to analyse executive functions already at preschool
      age. Preterm children are at risk of having subnormal levels of executive
      functioning, even though their general IQ is normal.

PMID- 15499960
TI  - Validation of a Dutch language screening instrument for 5-year-old preterm
      infants.
AB  - AIM: The validation of the Dutch Taal Screenings Test (TST), a language-screening
      test, which is included in a follow-up instrument developed to enable
      paediatricians to assess 5-y-old preterm infants for their motor, cognitive and
      speech and language development. METHODS: The speech and language development of
      145 5-y-old infants born before 32 wk of gestation and/or with a birth weight of
      less than 1500 g was assessed by a paediatrician using the TST and by a speech
      therapist using standardized language tests. RESULTS: All correlations between
      the instruments were significant. Using the original cut-off point of the TST for
      abnormal speech and language development (18 points), the paediatrician will only
      identify 62% of the children who need speech therapy. For this group of children,
      a cut-off point of 17 is more effective. The positive predictive value of the TST
      improved from 77% to 82% by using a parent and school questionnaire to evaluate
      in a more subjective way the speech and language development. CONCLUSION: Using
      the TST, paediatricians will be able to identify speech or language problems in 5
      y-old preterm infants.

PMID- 15499961
TI  - Prediction of academic and behavioural limitations in school-age survivors of
      bacterial meningitis.
AB  - AIM: To develop a prediction rule to identify postmeningitic children at high
      risk of academic and behavioural limitations. METHODS: 182 children (mean age 10
      y; range 5-14) were selected from a cohort of 674 school-age survivors of
      bacterial meningitis. These children had neither meningitis with "complex onset",
      nor prior cognitive or behavioural problems, nor severe disease sequelae. On
      average, 7 y after the meningitis, they were evaluated using an "Academic
      Achievement Test", and their parents filled in the "Child Behaviour Checklist".
      By reviewing the medical records, potential risk factors for academic and/or
      behavioural limitations were collected. Independent predictors were identified
      using multivariate logistic regression analysis, leading to the formulation of a
      prediction rule. RESULTS: The cumulative incidence of academic and/or behavioural
      limitations among children who survived bacterial meningitis without severe
      disease sequelae was 32%. The prediction rule was based on nine independent risk
      factors: gender, birthweight, educational level of the father, S. pneumoniae,
      cerebrospinal fluid leukocyte count, delay between admission and start of
      antibiotics, dexamethasone use, seizures treated with anticonvulsive therapy, and
      prolonged fever. When 10 was taken as a cut-off point for the risk score computed
      using this rule, 76% of the children with limitations could be identified, while
      38% of the children in the cohort were selected as at risk for these limitations.
      CONCLUSION: With a prediction rule based on nine risk factors, postmeningitic
      children at high risk of developing academic and/or behavioural limitations could
      be identified. Additional research is required to further validate this
      prediction rule. In the future, a careful follow-up of high risk children may
      enhance early detection and treatment of these limitations.

PMID- 15499962
TI  - Factors of early infancy and recurrent use of antibiotic therapy.
AB  - AIM: To analyse the role of early infant-related, parent-related, family
      functioning and social relation factors during the infant's first 3 mo of life
      and their associations with later recurrent treatments with antibiotics. METHODS:
      In an unselected population-based study, parents expecting their first child were
      followed from pregnancy until the infant was 18 mo of age. Informed consent to
      participate was obtained from 1443 women expecting their first child and their
      spouses. The parents of 817 children reported the number of preceding antibiotic
      treatments at two times (when the child was 9 and 18 mo old). The outcome measure
      was the number of antibiotic treatments (options: none, 1-5, > or = 6). The
      factors associated with later use of antibiotics were collected during the first
      3 mo of the infant's life. The variable factors included infant-related, parent
      related, family functioning and social relation factors. RESULTS: The final
      regression analysis showed the potent factors associated with recurrent use of
      antibiotics: male gender (OR 2.8, 95% CI: 1.6-4.8), frequent physician
      consultations in early infancy (OR 3.1, 95% CI: 1.8-5.3) and the father's need
      for outside support (OR 2.2, 95% CI: 1.3-3.8). CONCLUSIONS: In addition to early
      infant-related medical factors, family factors may be associated with frequent
      medical consultations and the decision to administer antibiotics to the infant.
      In the prevention of antibiotic overuse, social and psychological factors should
      be considered.

PMID- 15499964
TI  - Accelerated ventricular rhythm in the neonatal period: a review and two new cases
      in asymptomatic infants with an apparently normal heart.
AB  - Accelerated ventricular rhythm (AVR) was observed in two newborn infants. In the
      first case, arrhythmia was noted during the foetal period. Both neonates were
      asymptomatic and had no evidence of cardiac disease. The arrhythmia eventually
      disappeared when the infants were 4 mo and 24 d old, respectively. AVR in the
      neonatal period is reviewed in this report and recent information regarding
      appropriate diagnostic evaluation, differentiation from ventricular tachycardia
      and treatment is outlined. CONCLUSION: Accelerated ventricular rhythm is a benign
      and self-limited arrhythmia in the neonatal period. However, it is important to
      differentiate it from other serious rhythm disorders, mainly ventricular
      tachycardia, in order to avoid unnecessary and potentially harmful treatment and
      to relieve parental anxiety.

PMID- 15499963
TI  - The effects of iron deficiency on infants' developmental test performance.
AB  - AIM: To assess the effects of iron deficiency on developmental test scores in
      infants. METHODS: This prospective, single-blind, controlled clinical
      intervention study was made on 108 children aged 6-30 mo who applied to our
      paediatric outpatient clinic. The cases were classified as control (n = 31,
      haemoglobin > or = 11 g/dl, serum ferritin > 12 microg/l, MCV > or = 70 fl), non
      anaemic iron deficiency (NAID, n = 40, haemoglobin > or = 11 g/dl, serum ferritin
      < or = 12 microg/l, MCV > or = 70 fl) and iron deficiency anaemia (IDA, n = 37,
      haemoglobin < 11 g/dl, ferritin < or = 12 microg/l, MCV < 70 fl) due to their
      anaemia status. In each group, MCV, haemoglobin and ferritin levels were
      measured, and Denver Developmental Screening Test (DDST) and Bayley Scales of
      Infant Development (BSID-I) were administered before and after a 3-mo follow-up.
      IDA and about half of the NAID subjects were treated with oral iron for 3 mo.
      RESULTS: Subjects with iron deficiency showed significantly lower developmental
      test scores both with BSID-I and DDST-II compared to their iron-sufficient peers
      (p < 0.05). After 3 mo of iron treatment, lower mental developmental test scores
      were no longer observed among the IDA and NAID groups whose anaemia and iron
      deficiency were also corrected. No significant differences were found between
      control NAID and control IDA groups on DGTT-II results after treatment. The
      difference in motor and mental developmental scores did not appear to depend on
      environmental and family factors considered in the analyses. CONCLUSION: These
      findings support the conclusions that iron deficiency may cause lower mental and
      motor test scores in infants and these adverse effects can be improved by iron
      therapy.

PMID- 15499965
TI  - Cushing's syndrome in pregnancy and neonatal hypertrophic obstructive
      cardiomyopathy.
AB  - Cushing's syndrome is rare in pregnancy but can cause spontaneous abortion,
      stillbirth or premature birth. We report a case of transient hypertrophic
      obstructive cardiomyopathy in a newborn whose mother had hypercortisolism due to
      a primary adrenal lesion. There was no family history of hypertrophic obstructive
      cardiomyopathy. Follow-up revealed complete resolution of the cardiac
      abnormalities in the infant. Cushing's syndrome in the mother resolved after
      delivery. Although maternal hypercortisolism seldom results in symptomatic
      hypercortisolism in the newborn, hypertrophic obstructive cardiomyopathy can
      occur.

PMID- 15499966
TI  - Intractable congenital chylous ascites.
AB  - A male newborn presented with congenital chylous ascites, the treatment of which
      is difficult and complicated due to persistent loss of chyle. The primary
      therapeutic goal is to reduce the lymph flow and to allow the leakage to heal
      naturally. Usually, conservative management--enteric rest with total parental
      feeding or an enteral diet with medium-chain triglycerides--can achieve this. A
      new treatment option is the use of octeotride, a somatostatin analogue. Both
      therapies failed in our patient, and surgical ligation of the leaking lymphatic
      duct was successful. CONCLUSION: The success of the surgical treatment depends on
      localizing the leaking lymphatic duct. Lymphatic imaging with lymphoscintigraphy
      and pre-operative administration of lipophilic dye can assist the surgeon.

PMID- 15499967
TI  - Paroxetine during lactation: is it really safe for the infant?

PMID- 15499968
TI  - The mycotoxin fumonisin B1 transiently activates nuclear factor-kappaB, tumor
      necrosis factor alpha and caspase 3 via protein kinase Calpha-dependent pathway
      in porcine renal epithelial cells.
AB  - Fumonisin B1 (FB1) is a toxic mycotoxin produced by Fusarium verticillioides,
      predominantly present in corn. The principal biochemical responses of FB1 involve
      disruption of sphingolipid metabolism from the inhibition of ceramide synthesis
      leading to accumulation of free sphingoid bases, particularly sphinganine. The
      ability of FB1 to modulate signal transduction pathways plays a role in its
      toxicity. We recently reported that FB1 selectively and transiently activates
      protein kinase Calpha (PKCalpha) in porcine renal epithelial cells (LLC-PK1). The
      aim of current study was to investigate the effect of PKCalpha activation by FB1
      on NF-kappaB activation and subsequently on TNFalpha gene expression and caspase
      3 induction in LLC-PK1 cells. FB1 (1 micromol/L for 5 min) transiently activated
      PKCalpha and increased nuclear translocation of NF-kappaB, followed by their down
      regulation at later time points. Preincubating the cells with the PKC inhibitor,
      calphostin C, prevented the activation of NF-kappaB by FB1. TNFalpha mRNA
      expression was increased after 15 min exposure to FB1 or the PKC activator,
      phorbol 12-myristate 13-acetate. In addition, an increase in caspase 3 activity
      was observed after addition of FB1 for 1 h. Calphostin C prevented both the FB1
      induced increase in TNFalpha expression and caspase 3 activation. In summary, we
      hereby demonstrate that the FB1 activation of NF-kappaB and sequential induction
      of TNFalpha expression resulting in the subsequent increase in caspase 3 activity
      are all dependent on PKCalpha stimulation in LLC-PK1 cells.

PMID- 15499969
TI  - The effects of ochratoxin A on lipid peroxidation and antioxidant enzymes: a
      protective role of melatonin.
AB  - Various studies indicate that the mycotoxin ochratoxin A (OTA) is a carcinogenic,
      genotoxic, teratogenic, immunotoxic, and nephrotoxic agent. In the present study,
      the activities of some enzymes in the serum and liver of rats with ochratoxicosis
      and the effects of melatonin on these enzymes were investigated. Rats were
      divided into three equal groups, each consisting of eight rats; control, OTA (289
      microg/kg per day) and OTA + melatonin groups for this study. In the OTA treated
      group, the level of lipid peroxidation (LPO) and the activities of glutathione
      peroxidase (GSH-Px) were increased in the liver and serum in comparison with the
      control group. The activities of catalase (CAT) and superoxide dismutase (SOD)
      were significantly changed in the serum when compared with controls. Our results
      showed structural tissue damage in the liver in OTA-treated rats. Melatonin
      decreased the OTA-induced damage to support the antioxidant defense system and/or
      with free radical scavenger action.

PMID- 15499970
TI  - Effects of ambient air particles on nitric oxide production in macrophage cell
      lines.
AB  - We assessed the in vitro toxicity of various particles on three murine macrophage
      cell lines, (J774A.1, WR19M.1, RAW264.7). The cells were exposed to aqueous
      suspensions (0-100 microg/30 mm2 well) of urban particulate matter (SRM-1648, SRM
      1649, EHC-93), fine particulate matter (PM2.5), titanium dioxide (SRM-154b), and
      respirable cristobalite (SRM-1879) for 2 h and were then stimulated with
      lipopolysaccharide (LPS, 100 ng/ml) and recombinant interferon-gamma (IFN, 100
      U/ml). After overnight incubation with the particles and LPS/IFN, nitric oxide
      production was estimated from culture supernatant nitrite. Cell viability was
      determined by monitoring the rate of AlamarBlue reduction. The dose-effect
      relationships for nitrite and viability were modeled as a power function (Fold
      change = [Dose+1]beta), where beta represents the slope of the dose-response
      curve. Potency was defined as the rate of change in nitrite production corrected
      for cell viability (beta(POTENCY) = beta(NITRITE) - beta(VIABILITY)). Overall,
      the urban particles decreased nitric oxide production (beta(POTENCY) < 0), while
      exposure of the cells to fine particulate matter or cristobalite increased the
      production of nitric oxide (beta(POTENCY) > 0). Titanium dioxide (TiO2) was
      essentially inactive (beta(POTENCY) approximately to 0). The decrease in nitric
      oxide production seen in cells exposed to the urban particles was directly
      correlated to a decrease in the expression of inducible nitric oxide (iNOS) as
      determined by Western blot analysis. The results indicate that particles are
      modulators of nitric oxide production in murine macrophages and may directly
      disrupt expression of iNOS during concomitant pathogen exposure. Pathways leading
      to enhanced NO production causing cell injury, and to decreased NO release
      resulting in lower bacterial clearance, may both be relevant to the health
      effects of ambient particles.

PMID- 15499971
TI  - Zinc pretreatment prevents hepatic stellate cells from cadmium-produced oxidative
      damage.
AB  - Pretreatment with zinc produces tolerance to several cadmium toxic effects. This
      study was performed to further elucidate the mechanism of zinc-induced tolerance
      to cadmium cytotoxicity in a rat hepatic stellate cell line (CFSC-2G). Twenty
      four hours after seeding, cells were treated with 60 micromol/L ZnCl2 for 24 h.
      Following zinc pretreatment, cells were exposed to 3 micromol/L and 5 micromol/L
      CdCl2 for an additional 24 h. The toxicity of cadmium was significantly reduced
      in the zinc-pretreated cells. Zinc pretreatment produced a decrease in lipid
      peroxidation damage of cadmium-treated cells. Glutathione cell content diminished
      33% and 43% as a result of 3 micromol/L and 5 micromol/ L CdCl2 treatment,
      respectively. Cell pretreatment with zinc recovered glutathione content at
      control cells level. Catalase and glutathione peroxidase activities were also
      recovered to control values with zinc pretreatment. Cadmium (5 micromol/L) was
      able to induce 39% the expression of alpha1 collagen (I) gene after 1 h
      treatment, while zinc pretreatment prevented this cadmium profibrogenic effect.
      We also examined the production of heat shock protein 70 (Hsp70) as a cellular
      response to oxidative stress produced by cadmium. By Western blot analysis, a 1.3
      and 3 times increment in Hsp70, with 3 micromol/L and 5 micromol/L CdCl2
      treatment, respectively, was observed. Zinc pretreatment prevented the production
      of Hsp70. Metallothionein-II (MT-II) gene expression was induced by cadmium, but
      the induction was unaffected with zinc pretreatment. These data suggest that zinc
      induced protection against the cytotoxicity of cadmium in stellate cells may be
      related to the maintenance of normal redox balance inside the cell.

PMID- 15499972
TI  - Influence of organosulphur compounds from garlic on the secretion of matrix
      metalloproteinases and their inhibitor TIMP-1 by cultured HUVEC cells.
AB  - Organosulphur compounds from garlic, especially diallyl disulphide (DADS) at non
      toxic concentrations, affected production and secretion of some matrix
      metalloproteinases (MMPs) and of tissue inhibitor of metalloproteinase-1 (TIMP
      1), one of their inhibitors, by human umbilical vein endothelial cells. Addition
      of DADS to the culture medium resulted in a concentration-dependent reduction of
      secreted MMP-2 protein and activity as well as TIMP-1 protein. In the presence of
      inducers (phorbol 12-myristate 13-acetate, forskolin and tumor necrosis factor
      alpha) addition of DADS caused a distinct concentration-dependent decrease of MMP
      9 and TIMP-1 secretion, while not affecting MMP-9 mRNA levels. Intracellular
      protein levels remained low and were not affected. Other organosulphur compounds
      like allyl mercaptan and S-allylcysteine showed no or less clear effects on MMP
      secretion or TIMP-1-secretion. These results suggest that DADS may mediate some
      of the biological effects ascribed to garlic preparations through affecting MMP
      TIMP balance.

PMID- 15499973
TI  - [Intratympanic dexamethasone injections for intractable Meniere's disease].
AB  - OBJECTIVE: To investigate the efficacy of intratympanic dexamethasone injections
      (IDI) for 15 patients with intractable Meniere's disease (MD). METHOD:
      Dexamethasone (2.5 mg/0.5 ml) was injected into the middle ear and followed by a
      second injection 15 minutes later. The injection was repeated the next day and
      weekly for 3 weeks. Total dose of dexamethasone was 17.5 mg. RESULT: The 15
      patients were followed up for 18 months (average). Complete relief of vertigo was
      maintained in 10 cases, improved in 2 case, injection wos repeated 3 patients
      with recurrent vertigo resulted in control of vertigo. Tinnitus disappeared in 5
      cases, reduced in 5 cases, unchanged in 5 cases. Hearing was improved in 10
      cases, unchanged in 5 cases. CONCLUSION: IDI is effective for intractable MD. The
      benefits of IDI are avoidance of systemic use of steroids, lower cost, easy
      application. IDI can be used as an initial surgical treatment for persistent
      vertigo in MD and indicated for bilateral MD.

PMID- 15499974
TI  - [CO2 laser assisted stapedotomy with artificial stapes prosthese].
AB  - OBJECTIVE: To apply CO2 laser assisted Ugo Fisch stapedotomy with artificial
      stapes prostheses and to observe its outcome. METHOD: Between October 2001 and
      June 2003, 24 patients with clinical diagnosis of otosclerosis were performed
      with CO2 laser assisted Ugo Fisch stapedotomy. Among them 14 were males and 10
      were females with a age of 24-65 years (averaged 36.5 years). The preoperative
      air bone gap of speech frequency is 25.00 to 48.25 dB, with an average of 36.25
      dB. Follow-up was done once two months until 6 months. The key techniques are:
      (1) first disarculate the incudostapedial joint; (2) 0.3 mm or 0.4 mm piston is
      selected according to the space between horizontal segment of facial nerve and
      the suprastructure of stapes; (3) fenestrate on the footplate, insert the piston
      before dealing with stapedial muscle tendon and suprastructure of stapes; (4)
      deal with stapedial muscle tendon and suprastructure of stapes with CO2 laser.
      RESULT: A postoperative air bone gap < or = 15 dB is achieved in 23 cases
      (95.8%), a postoperative air bone gap < or = 10 dB is achieved in 21 cases
      (87.5%), with a mean of 8.5 dB. The postoperative complication is slight, without
      sickness and vomit, and 22 patients could walk immediately after surgery.
      CONCLUSION: CO2 laser assisted stapedotomy is the first choice for treating
      otosclerosis, which is of significant outcome, high safety and slight
      postoperative complication.

PMID- 15499975
TI  - [Enlarged translabyrinthine resection of recurrent acoustic neuroma after
      suboccipital resection].
AB  - OBJECTIVE: To evaluate the technique and the outcome of enlarged
      translabyrinthine removal of recurrent acoustic neuromas after a suboccipital
      resection. METHOD: Five patients were proved to have recurrent acoustic neuromas
      after previous suboccipital removal procedures. Revision surgery was accomplished
      in these patients using the enlarged translabyrinthine approach by sufficiently
      removing petrous temporal bone to enlarge exposed sight during the operation.
      RESULT: The sizes of the recurrent tumors ranged from 2.5 to 4.0 cm. Total
      removal was achieved in all patients, with no death and other major complications
      such as intracranial infection and cerebrospinal fluid leakage. The facial nerve
      function was the same as pre-operative condition. There was no residual tumor
      showed in CT scans and MRI examinations after operation. The cerebel and
      brainstem resumed to normal position in each patient. No second recurrences had
      occurred to date at follow-up of 6 months to 2 years and 7 months. All patients
      recuperated and came back to work. CONCLUSION: Acoustic neuroma recurs frequently
      after the suboccipital surgery because there is a residual tumor inside the
      internal acoustic canal (IAC). The enlarged translabyrinthine approach is the
      most direct access to acoustic neuroma and the brainstem by which recurrent tumor
      can be removed is avoided during the second operation. Moreover, it is praisable
      that there are several advantages such as slight invasion and convenience of
      facial nerve orientation so as to excellent outcome of facial nerve preservation
      in the enlarged translabyrinthine surgery.

PMID- 15499976
TI  - [The saccular function in Meniere's disease].
AB  - OBJECTIVE: To record and analyze the vestibular evoked myogenic potentials (VEMP)
      in Meniere's disease. METHOD: VEMP in 15 patients diagnosed as Meniere's disease
      were investigated and made out different kinds of manifestation of VEMP. The
      results of VEMP were compared with these caloric test. RESULT: The wave of p13
      and n23 appeared 100% in normal subjects, but only appeared 30% in Meniere's
      disease. There were 3 kinds of manifestation of VEMP-normal response, bilateral
      no response and lower amplitude in hydrops side. CONCLUSION: Membranous hydrops
      in Meniere's disease may damage the saccular function and VEMP test may be
      helpful for diagnosis of Meniere's disease.

PMID- 15499977
TI  - [The role of high-resolution CT in the preoperative assessment of chronic otitis
      media].
AB  - OBJECTIVE: To assess the high-resolution CT scan in depicting the middle ear
      structures. METHOD: The surgical findings of 51 ears operated on were
      retrospectively compared with the CT findings. The followings were analysed:
      diagnostic features of chronic otitis media (COM) on CT status of the middle ear
      structures (ossicles, facial nerve canal, semicircular canals and tegmen
      tympani), and anatomical variations. RESULT: The radio-surgical agreement was
      excellent for the malleus (kappa statistics, k = 0.840) and tegmen (0.788), good
      for the incus (0.700) and semicircular canals (0.56), but poor for the stapes
      (0.366) and facial nerve dehiscence (0.310). Potential surgical hazards detected
      by the scans included: Low lying dura, high jugular bulb, anterior lying sigmoid
      sinus, facial nerve dehiscence and other situations brought about by the
      destructive nature of the lesion. CONCLUSION: There is a good radio-surgical
      correlation in COM for most middle ear structures except for the integrity of the
      facial canal and stapes. The scan alerts the surgeon the potential surgical
      dangers and complications of disease. High-resolution CT scan should be a routine
      examination prior to middle ear and mastoid surgery.

PMID- 15499978
TI  - [Magnetic resonance imaging study and cochlear implantation in post-meningitic
      deaf patients].
AB  - OBJECTIVE: To investigate the clinical application of magnetic resonance imaging
      (MRI) in post-meningitic patients and its impact on surgical decision. METHOD:
      The pre-operative MRI data and auditory brainstem response (ABR) examination of
      five post-meningitic patients were studied. They were implanted with cochleas.
      RESULT: The interval between the onset of bacterial meningitis and the hearing
      loss was (15.8 +/- 15.0)d and it was longer in children than adults. Five ears
      showed membranous cochlear labyrinth abnormality; 3 ears had vestibule vestibule
      abnormality; 8 ears demonstrated semicircular canal abnormality on MRI
      examinations in totally 10 ears. The mean hearing threshold of 10 ears was (102.0
      +/- 7.1)dB HL,that of the operated ears was (98.0 +/- 5.7)dB HL and that of the
      un-operated ears was (106.0 +/- 6.5)dB HL. It was (15.8 +/- 15.0)d from the
      bacterial meningitis onset to hearing loss. The interval is longer in children
      than adults. There were 3 ears that electrodes could not be inserted completely.
      CONCLUSION: The bacterial meningitis may cause the abnormalities of inner ears
      and the MRI before surgery is essential for the pre-operative planning of
      cochlear implant.

PMID- 15499979
TI  - [Review of cochlear implantation in 110 cases].
AB  - OBJECTIVE: To summarize the operation experiences in cochlear implantation.
      METHOD: Multiple channel electrodes were implanted in 110 patients with severe
      hearing loss or total deaf. RESULT: One hundred percentage of successful
      implantation was achieved, and the average hearing level of tone stimulation is
      37.6 dB SPL. CONCLUSION: Careful examination in audiology and imagiology pre
      operation is very important in achieving the successful operation with the best
      hearing rehabilitation results.

PMID- 15499980
TI  - [The pathogeny and treatment of hemifacial spasm].
AB  - OBJECTIVE: To find out the etiopathogenesis of hemifacial spasm, and to research
      the principles and methods of surgical treatment. METHOD: The micro-surgical
      relationships between facial nerve and adjacent vessels were examined in 30
      adults cadavers. One hundred and twenty cases of hemifacial spasm were treated
      through posterior fossa microsurgery, twenty of which received microvascular
      decompression, sixty-eight by combing of facial nerve, and thirty-two by both
      microvascular decompression and combing. RESULT: Forty-one out of the 60 facial
      nerves in 30 adults cadavers were observed to have been in touch with arteries
      for 42 times,accounting for 68.3% of the cases. In 120 operations, 56 facial
      nerves were found to be compressed or distorted by the arteries. One hundred and
      twenty cases were followed up for 3 years. Five recurrent cases were found in 20
      cases operated by microvascular decompression, 10 recurrent cases in 68 cases
      operated by combing of facial nerve and 2 recurrent cases in 32 cases operated by
      both microvascular decompression and combing. CONCLUSION: Vascular compression is
      a cause of the hemifacial spasm, but not the only one. This paper pointed out the
      importance of selecting suitable treatment for the patient individually.

PMID- 15499981
TI  - [Adjuvant treatment of anisodamine to acute serous otitis media].
AB  - OBJECTIVE: To evaluate the adjuvant treatment of anisodamine to acute serous
      otitis media. METHOD: Sixty-one acute otitis media patients were divided randomly
      into two groups. Group A with 30 patients were treated with 1% ephedrine
      nosedrop, antibiotic and antihistamine. Group B with 30 patients were treated
      with 1% ephedrine nose drops, antibiotic, antihistamine and anisodamine. They
      took anisodamine 10 mg twice a day. Then the treating efficiency of group A was
      compared with that of group B in 5 days and 10 days respectively. RESULT: The
      symptoms including hearing loss, tinnitus, hydrotympanum and eustachian tube
      function of group B recover more guickly than that of group A. CONCLUSION:
      Anisodamine adjuvant treatment of acute serous otitis media by improving the
      function of eustachian tube and microcirculation.

PMID- 15499982
TI  - [The effects of tympanotomy tube insertion on distortion product otoacoustic
      emissions].
AB  - OBJECTIVE: To discuss the effects of tympanotomy tube insertion on distortion
      product acoustic emissions. METHOD: Twenty-six patients (29 ears) with B type of
      tympanogram and conductive hearing loss but their bone conductive threshold was
      less than 30 dB were selected and recorded the DPOAE audiogram with Smart OAE4.24
      otodymic analyser before, shortly after and two weeks after tube insertion.
      Twelve normal subjects were selected as control. RESULT: The eliciting rate and
      amplitude increased after tube insertion. The difference in 1105, 1560, 2211,
      4416 Hz were significant. The amplitude went up two weeks later. CONCLUSION: The
      amplitude of DPOAE can be influenced by otitis media with effusion, tympanic
      membrane perforation and tympanotomy tube, and improved after tympanotomy tube
      insertion, but it can't reach the normal level.

PMID- 15499983
TI  - [The expression of RANTES interleukin 1beta and endotoxin in the effusion of
      secretory otitis media].
AB  - OBJECTIVE: To study the protein expression of endotoxin, interleukin 1beta (IL
      1beta) and regulated upon activation, normal T expressed and secreted (RANTES) in
      effusions of secretory otitis media and their roles in the pathogenesis of
      secretory otitis media. METHOD: Seventy-two effusion samples were taken from 53
      patients with secretory otitis media by tympanocentesis. After swabs they were
      taken for bacteria culture. Limulus amebocyte lysate (LAL) test was used to
      quantify the content of endotoxin, radioimmunoassay to analyze the level of IL
      1beta and enzyme-linked immunosorbent assay (ELISA) to detect the concentration
      of RANTES. RESULT: Endotoxin, IL-1beta and RANTES were detectable in 80.9%, 77.8%
      and 70.8% of middle ear effusion, with mean levels of (35.2 +/- 51.6) EU/ml,
      (1.10 +/- 0.84) microg/L and (0.52 +/- 0.43) microg/L respectively. All of them
      showed higher concentration in the mucoid-type effusions than those in the serous
      type effusions (P<0.05). Higher levels of the endotoxin and RANTES (P<0.05) were
      found in longer course patients. The effusions with positive bacteria culture
      displayed more abundant endotoxin, IL-1beta and RANTES protein than those with
      negative culture. Significant correlations were found between endotoxin and IL
      1beta (r = 0.74, P<0.01), also between IL-1beta and RANTES (r = 0.48, P<0.01).
      CONCLUSION: Endotoxin, IL-1beta and RANTES may take part in maintaining the
      inflammatory response in the tympanic cavity and stimulating mucin secretion. It
      indicates that they play an important role in the immune pathogenesis of
      secretory otitis media.

PMID- 15499985
TI  - [Surgery of parapharyngeal space neoplasms].
AB  - OBJECTIVE: To study the diagnosis, treatment and the choice of operative entrance
      for parapharyngeal space neoplasm. METHOD: In a retrospective study the data of
      34 patients between 1993 and 2002 were analyzed with regard to presenting signs
      and symptoms, histological diagnosis, imaging technique and surgical approach.
      RESULT: 88.2% of the tumors were benign. Sixteen tumors originated from salivary
      glands. Neurogenic tumors were found in 14 patients. Thirty-four patients were
      treated surgically: the trans-cervical approach was used in 26 cases, trans-oral
      in 5 cases, the combined transoral-cervical approach in 2 cases, and trans
      infratemporal fossa in 1 case. Thirty-two tumors were removed completely. The
      complications after operation were Horner syndrome (3 cases), vocal cord
      paralysis (5 cases) and facial nerve palsy (3 cases). One patient had both vocal
      cord paralysis and hypoglossal nerve paralysis. With the follow-up time of 13
      months to 10.5 years, 30 patients had been cured, one patient turned to better, 3
      cases had recurrence local tumour (pleomorphic adenoma). CONCLUSION: The majority
      of tumors can be excised safely and completely using the trans-cervical approach.
      Intra-oral excisions should be indicated only for small tumors that tend to
      pharynx with clear border.

PMID- 15499984
TI  - [Carbogen combined with drugs in the treatment of sudden deafness].
AB  - OBJECTIVE: To analyze the clinical efficiency and study the possible mechanism of
      the carbogen combined with drugs in the treatment of sudden deafness. METHOD:
      Fifty-two patients with sudden deafness were divided into two groups: Twenty-six
      cases received carbogen (5% CO2 - 95% O2) combined with drug therapeutics of a
      course of intravenous administration of dexamethasone, vitaminB, low molecular
      dextran, salviae miltiorrhizae, and intake vitaminC, vitaminE, et al and the
      other 26 cases received the drugs only. The clinical effects were compared.
      RESULT: The total effective rate was 76.92% in the carbogen group and 50.00% in
      the control group. The difference was significant between the two groups. The
      recovery time in the carbogen group was 3-14 days while in the control group was
      6-23 days. CONCLUSION: The efficiency of carbogen ombined with drugs is superior
      to drug therapeutics in the treatment of sudden deafness.

PMID- 15499986
TI  - [Security assortment and guarding method after tracheotomy].
AB  - OBJECTIVE: To discuss the assortment method of security and to find out measures
      in order to avoid the asphyxia death owing to obstruction and collapse of canal
      after tracheotomy. METHOD: During the period from June 1998 to September 2003,
      346 patients were operated the tracheotomy for different reasons. Then they were
      assorted according to the causes if there was an obstruction in superior airway,
      the patients' mental health, age and the capacity of saving themselves. We
      divided them into three kinds, which were security, dangerousness (temporalily or
      permanently) and relative dangerousness. The corresponding methods of operation
      therapy and nursing care had been proposed. RESULT: One hundred and sixty cases
      were the secure kind; 17 cases the dangerous kind (12 cases permanently, 5 cases
      temporalily), 169 cases the relatively dangerous kind. After adopting
      corresponding method of operation and nursing cars, the asphyxia death due to
      obstruction or collapse of canal didnt happen. CONCLUSION: The security
      assortment has significance after tracheotomy for reducing the asphyxia death
      rate.

PMID- 15499988
TI  - [The expression of matrix metalloproteinase-9 and tumor necrosis factor-alpha in
      cholesteatoma].
AB  - OBJECTIVE: To observe the expression of MMP-9, TNF-alpha in cholesteatoma and to
      determine their roles in the destruction of bone. METHOD: Immunohistochemical
      method (SP) and the computer image quantitative analysis were used to examine the
      expression of TNF-alpha, MMP-9 in 22 samples from cholesteatoma and 20 normal
      cases. At the same time, the correlation between the expressions of the two
      indexes and the erosion of ossicles were observed. RESULT: MMP-9 protein was only
      expressed in cholesteatoma stromal cells. TNF-alpha was expressed in both
      epithlium and stromal cells. The results of the computer image quantitative
      analysis showed that the mean optical density of MMP-9 and TNF-alpha in
      cholesteatoma were higher than that in normal skin epithelial tissue (P < 0.05),
      in addition, the two indexes were relative to the extent of ossicle destruction.
      CONCLUSION: MMP-9 and TNF-alpha are overexpressed in cholesteatoma and they are
      associated with ossicle destruction, which shows that MMP-9 and TNF-alpha are
      responsible for bone destruction in cholesteatoma; MMP-9 and TNF-alpha have a
      correlation in their expression, which suggest that the two factors act on each
      other possibly; Overexpression of MMP-9 is only observed in stromal cells and the
      immunostain of TNF-alpha also is observed in stromal cells which indicates that
      stromal cells play an important role in bone destruction.

PMID- 15499987
TI  - [Expression of cyclooxygenase-2 and p53 and their correlation in carcinoma of
      larynx].
AB  - OBJECTIVE: To study the expression of cyclooxygenase-2 in laryngeal squamous
      carcinoma and evaluate the relation between cyclooxygenase-2 and p53. METHOD: The
      pathological sections of laryngeal squamous carcinoma was examined by using the
      method of immunohistochemistry. RESULT: Overexpression of Cox-2 and p53 were
      found in the laryngeal squamous carcinoma specimens; the positive rates of
      cyclooxygenase-2 and p53 protein expression were 58.7% (37/63) and 63.5% (40/63),
      respectively. The positive expressions of Cox-2 were related to the clinical
      stage. The positive expressions of p53 were related to histological grade. There
      was a positive relationship between Cox-2 and p53. CONCLUSION: Cyclooxygenase-2
      plays an important roles in the process of development, growth and invasion of
      laryngeal squamous carcinoma; and its inhibitors maybe have effect on the
      development of laryngeal squamous carcinoma.

PMID- 15499989
TI  - [The expressions and correlations of RAR-beta receptors and galectin-8 in human
      middle ear cholesteatoma].
AB  - OBJECTIVE: To explore the expression and correlation of RAR-beta receptor and
      galectin-8 in acquired middle ear cholesteatoma, and to evaluate their roles in
      the formation of middle ear cholesteatoma. METHOD: Tissue specimens from 42 cases
      of acquired middle ear cholesteatoma and 18 cases of external ear skin were
      examined by immunohistochemical SABC method for RAR-beta receptors and galectin
      8, also by Western Blot for these two factors. RESULT: All 42 samples of
      cholesteatoma showed a stronger expression of RAR-beta receptor than the external
      ear skin. The mean optical absorbency density of RAR-beta receptor in the two
      types of tissues were 0.2734 +/- 0.0022, respectively, with statistically
      significant difference between them. RAR-beta receptor expressed in the cytoplasm
      and membrane of the full epithelial tissue, and not remarkably expressed in the
      external ear skin cells. Beside the basal cell layers, keratinocytes of the
      suprabasal cell layers were found to contain galectin-8 expression. The mean
      optical density of galectin-8 in the two types of tissues were 0.2826 +/- 0.0016
      and also with statistically significant difference between them. Furthmore, the
      level of RAR-beta expression correlated highly (P < 0.01) with the level of
      galectin-8 expression. CONCLUSION: An undifferentiated population of
      keratinocytes may lead to the formation of cholesteatoma, and a relation may
      exist between retinoid activity and galectins.

PMID- 15499990
TI  - [The clinical characteristic of electroglottography curves of pathological voice
      in adult].
AB  - OBJECTIVE: To discuss the clinical characteristic of Electroglottography (EGG)
      curves of pathological voice in adult. METHOD: Four hundred and fifty-three
      adults with pathological voices were examined by EGG and the abnormal EGG curves
      were analyzed. RESULT: (1) the EGG cycle was composed of contact phase (CP) and
      open phase (OP), the ratio of CP/OP was between 0.70 to 2.95, otherwise it was
      abnormal; (2) the CP was composed of closing-contact phase (CCP) and contact
      opening phase (COP); the OP was composed of opening-open phase (OOP) and open
      closing phase (OCP); (3) the abnormal formations of every phases in vibration
      cycle contained: smooth CCP, notches in CCP, flat in wave peak, steep COP,
      notches in COP, knurls in COP, knurls in OOP and in OCP; duplicate waves and
      irregular waves were fewer, but they reflected the special vibratory patterns of
      pathological voices; (5) Each abnormal formation fell as the follow: COP>OP>CCP.
      Each pathological voices presented different characteristics; (6) combined
      variance appeared in part pathological voices, such as single vocal polyps,
      double vocal polyps, Reinke edema and glottic laryngocarcinoma. COP combined with
      OOP was the most usual. CONCLUSION: The abnormal variance formations of EGG
      curves of pathological voices in adult are intricate and they have inherent
      relations with each other. The establishment of OP variance increases the
      pathological EGG and the OP abnormities is CP abnormities. There are different
      orientations and rules in different pathological voices.

PMID- 15499991
TI  - Heme oxygenase-1 as a protective gene.
AB  - Heme oxygenases catalyze the rate-limiting step in heme degradation, resulting in
      the formation of carbon monoxide, iron and biliverdin that is subsequently
      reduced to bilirubin by biliverdin reductase. The products of this enzymatic
      reaction have important biological effects, including antioxidant, anti
      inflammatory and cytoprotective functions. Three isoforms of heme oxygenase (HO)
      have been described: two constitutively expressed isoforms, HO-2 and HO-3, and an
      inducible isoform, HO-1 that is increased as an adaptive response to several
      injurious stimuli including heme, hyperoxia, hypoxia, endotoxin and heavy metals.
      Induction of HO-1 has been implicated in numerous clinically relevant disease
      states including transplant rejection, hypertension, atherosclerosis, lung
      injury, endotoxic shock and others. This review will focus on the protective
      functions of HO-1.

PMID- 15499992
TI  - [Pathophysiology and genetics of obesity].
AB  - Obesity has become the most prevalent nutritional disorder in post-industrialised
      societies and it is associated with the development of severe and costly
      complications such as type 2 diabetes mellitus and coronary heart disease or
      cancer. A large proportion of the risk of obesity is determined by the genetic
      susceptibility of an individual, but environmental factors conducive for the
      disorder play an important role in its phenotypic expression. Several candidate
      genes emerged from studies in animal models of obesity, but human pathophysiology
      is likely to be more complex. Thus, most cases of human obesity probably result
      from subtle interactions of susceptibility genes with environmental factors
      favouring deposition of excess calories as fat. The recent surge of obesity may
      relate to past evolutionary pressure which favoured selection of mechanisms
      defending body-weight against caloric restriction rather than against caloric
      excess. Rapidly developing new techniques in quantitative genetics and growing
      information from functional genomics will help to understand the interaction of
      environmental factors with signalling networks that regulate energy metabolism.
      The role of previously unknown pathways in the aetiology of obesity will be
      uncovered. The typing of numerous genetic variants will become possible and allow
      individual risk assessment for obesity and/or its associated disorders. Thus,
      rational and individually tailored therapies may be developed to combat obesity
      and its associated disorders.

PMID- 15499993
TI  - Carbonic anhydrases: current state of the art, therapeutic applications and
      future prospects.
AB  - Carbonic anhydrases (CAs, EC 4.2.1.1) are wide-spread enzymes, present in mammals
      in at least 14 different isoforms. Some of these isozymes are cytosolic (CA I, CA
      II, CA III, CA VII, CA XIII), others are membrane-bound (CA IV, CA IX, CA XII and
      CA XIV), CA V is mitochondrial and CA VI is secreted in the saliva and milk.
      Three cytosolic acatalytic forms are also known (CARP VIII, CARP X and CARP XI).
      The catalytically active isoforms, which play important physiological and patho
      physiological functions, are strongly inhibited by aromatic and heterocyclic
      sulfonamides. The catalytic and inhibition mechanisms of these enzymes are
      understood in great detail, and this greatly helped the design of potent
      inhibitors, some of which possess important clinical applications. The use of
      such CA inhibitors (CAIs) as antiglaucoma drugs are discussed in detail, together
      with the recent developments that led to isozyme-specific and organ-selective
      inhibitors. A recent discovery is connected with the involvement of CAs and their
      sulfonamide inhibitors in cancer: many potent CAIs were shown to inhibit the
      growth of several tumor cell lines in vitro and in vivo, thus constituting
      interesting leads for developing novel antitumor therapies. Future prospects for
      drug design of inhibitors of these ubiquitous enzymes are dealt with. Although
      activation of CAs has been a controversial issue for some time, recent kinetic,
      spectroscopic and X-ray crystallographic experiments offered an explanation of
      this phenomenon, based on the catalytic mechanism. It has been demonstrated
      recently, that molecules that act as carbonic anhydrase activators (CAAs) bind at
      the entrance of the enzyme active site participating in facilitated proton
      transfer processes between the active site and the reaction medium. In addition
      to CA II-activator adducts, X-ray crystallographic studies have been also
      reported for ternary complexes of this isozyme with activators and anion (azide)
      inhibitors. Structure-activity correlations for diverse classes of activators is
      discussed for the isozymes for which the phenomenon has been studied, i.e., CA I,
      II, III and IV. The possible physiological relevance of CA activation/inhibition
      is also addressed, together with recent pharmacological/ biomedical applications
      of such compounds in different fields of life sciences.

PMID- 15499994
TI  - The bicarbonate transport metabolon.
AB  - To allow cells to control their pH and bicarbonate levels, cells express
      bicarbonate transport proteins that rapidly and selectively move bicarbonate
      across the plasma membrane. Physical interactions have been identified between
      the carbonic anhydrase isoform, CAII, and the erythrocyte membrane Cl- /HCO3(-)
      anion exchanger, AE1, mediated by an acidic motif in the AE1 C-terminus. We have
      found that the presence of CAII attached to AE1 accelerates AE1 HCO3(-) transport
      activity, as AE1 moves bicarbonate either into or out of the cell. In efflux mode
      the presence of CAII attached to AE1 will increase the local concentration of
      bicarbonate at the AE1 transport site. As bicarbonate is transported into the
      cell by AE1, the presence of CAII on the cytosolic surface accelerates transport
      by consumption of bicarbonate, thereby maximizing the transmembrane bicarbonate
      concentration gradient experienced by the AE1 molecule. Functional and physical
      interactions also occur between CAII and Na+/HCO3(-) co-transporter isoforms NBC1
      and NBC3. All examined bicarbonate transport proteins, except the DRA (SLC26A3)
      Cl-/HCO3(-) exchange protein, have a consensus CAII binding site in their
      cytoplasmic C-terminus. Interestingly, CAII does not bind DRA. CAIV is anchored
      to the extracellular surface of cells via a glycosylphosphatidyl inositol
      linkage. We have identified extracellular regions of AE1 and NBC1 that directly
      interact with CAIV, to form a physical complex between the proteins. In summary,
      bicarbonate transporters directly interact with the CAII and CAIV carbonic
      anhydrases to increase the transmembrane bicarbonate flux. The complex of a
      bicarbonate transporter with carbonic anhydrase forms a "Bicarbonate Transport
      Metabolon."

PMID- 15499995
TI  - Quantum theoretic QSAR of benzene derivatives: some enzyme inhibitors.
AB  - Our previously developed approach to the development of QSAR equations for
      benzene derivatives, originally for phenylalkylamine hallucinogens, has been
      applied to four new systems: sulfonamide inhibitors of the enzymes carbonic
      anhydrase, thrombin, trypsin, and Clostridium histolyticum collagenase. The novel
      features involve the energies and nodal orientations of pi-like orbitals, and an
      allowance for the symmetry of the benzene nucleus. The resulting equations give
      better fits, better predictivity and are more easily interpretable than those
      resulting from traditional QSAR methods.

PMID- 15499996
TI  - Plasmodium falciparum carbonic anhydrase is a possible target for malaria
      chemotherapy.
AB  - Plasmodiumfalciparum is responsible for the majority of life-threatening cases of
      human malaria. The global emergence of drug-resistant malarial parasites
      necessitates identification and characterization of novel drug targets. Carbonic
      anhydrase (CA) is present at high levels in human red cells and in P. falciparum.
      Existence of at least three isozymes of the alpha < class was demonstrated in P.
      falciparum and a rodent malarial parasite Plasmodium berghei. The major isozyme
      CA1 was purified and partially characterized from P. falciparum (PfCA1). A search
      of the malarial genome database yielded an open reading frame similar to the
      alpha-CAs from various organisms, including human. The primary amino acid
      sequence of the PfCA1 has 60% identity with a rodent parasite Plasmodium yoelii
      enzyme (PyCA). The single open reading frames encoded 235 and 252 amino acid
      proteins for PfCA1 and PyCA, respectively. The highly conserved active site
      residues were also found among organisms having alpha-CAs. The PfCA1 gene was
      cloned, sequenced and expressed in Escherichia coli. The purified recombinant
      PfCA1 enzyme was catalytically active. It was sensitive to acetazolamide and
      sulfanilamide inhibition. Kinetic properties of the recombinant PfCA1 revealed
      the authenticity to the wild type enzyme purified from P. falciparum in vitro
      culture. Furthermore, the PfCA1 inhibitors acetazolamide and sulfanilamide showed
      good antimalarial effect on the in vitro growth of P. falciparum. Our molecular
      tools developed for the recombinant enzyme expression will be useful for
      developing potential antimalarials directed at P. falciparum carbonic anhydrase.

PMID- 15499997
TI  - In vitro inhibition effects of some new sulfonamide inhibitors on human carbonic
      anhydrase I and II.
AB  - A new series of aromatic and heterocyclic sulfonamides, including six new
      derivatives, 2-(3-cyclohexene-1-carbamido)-1,3,4-thiadiazole-5-sulfonamide
      (CCTS), 4-(3-cyclohexene-1-carbamido) methyl-benzenesulfonamide (CCBS), 2-(9
      octadecenoylamido)-1,3,4-thiadiazole-5-sulfonamide (ODTS), 2-(4,7,10-trioxa
      tetradecanoylamido)-1,3,4-thiadiazole-5-sulfonamide (TDTS), 2-(coumarine-3
      carbamido)-1,3,4-thiadiazole-5-sulfonamide (COTS) and 2-(8-methoxycoumarine-3
      carbamido)-1,3,4-thiadiazole-5-sulfonamide (MCTS), has been investigated. These
      sulfonamides were assayed for inhibition of human carbonic anhydrase I (hCA-I)
      and human carbonic anhydrase II (hCA-II) which were purified by affinity
      chromatography.

PMID- 15499998
TI  - Carbonic anhydrase inhibitors: Schiff's bases of aromatic and heterocyclic
      sulfonamides and their metal complexes.
AB  - Schiff's bases were obtained from aromatic/heterocyclic sulfonamides and amino
      sulfonamide derivatives, such as sulfanilamide, homosulfanilamide, 4-aminoethyl
      benzenesulfonamide and 5-amino-1,3,4-thiadiazole-2-sulfonamide. Metal complexes
      of some of these Schiff's bases, incorporating Zn(II), Co(lI), Ni(II) and Cu(II)
      ions, were also prepared and tested as inhibitors of the zinc enzyme carbonic
      anhydrase (CA), and more specifically the red blood cell isozymes I and II. The
      Schiff's bases behaved as medium potency CA I and CA II inhibitors, whereas their
      metal complexes showed a highly enhanced potency, with several low nanomolar CA
      II inhibitors detected.

PMID- 15499999
TI  - Benzolamide is not a membrane-impermeant carbonic anhydrase inhibitor.
AB  - Benzolamide, an orphan drug belonging to the pharmacological class of sulfonamide
      carbonic anhydrase (CA, EC 4.2.1.1) inhibitors (CAIs) is widely used in many
      physiological and pharmacological studies, together with the clinically employed
      classical drugs, acetazolamide, methazolamide, ethoxzolamide or
      dichlorophenamide, it being frequently stated that benzolamide is a membrane
      impermeant inhibitor. We prove here that this is false: in fact benzolamide is
      rather similar to acetazolamide from the point of view of penetrability through
      blood red cell membranes. Unlike these neutral drugs, the cationic, positively
      charged CAIs incorporating either tetraalkyl ammonium or pyridinium moieties, due
      to their salt-like character are indeed membrane-impermeant, being the only type
      of low molecular weight compound possessing such properties. Selective inhibition
      of membrane-associated CA isozymes is relevant indeed in many physiological
      studies and also pharmacologically, since the tumor-associated isozymes (CA IX
      and XII) are both membrane-bound.

PMID- 15500000
TI  - Carbonic anhydrase inhibitors: aliphatic N-phosphorylated sulfamates--a novel
      zinc-anchoring group leading to nanomolar inhibitors.
AB  - A small library of phosphorylated sulfamates (N-(O-alkylsulfamoyl)-phosphoramidic
      acids) incorporating long aliphatic chains (C8-C16) has been synthesized and
      investigated for their interaction with two physiologically relevant carbonic
      anhydrase (CA) isozymes. These compounds behaved as very potent inhibitors of
      both isozymes, with inhibition constants in the range of 8.2-16.1nM against
      isozyme hCA I, and 5.3-11.9nM against isozyme hCA II. Activity was optimal for
      the n-octyl derivative (similarly with that of the corresponding unsubstituted
      sulfamates) and gradually decreased for the longer chain derivatives. Some of
      these compounds are much more effective CA inhibitors as compared to the
      clinically used derivatives acetazolamide, sulfanilamide or topiramate, which are
      used as standards for the enzymatic determinations. The phosphorylated sulfamate
      moiety represents a novel zinc-binding group for the design of effective CA
      inhibitors.

PMID- 15500001
TI  - Effects of leptin and insulin on CA III expression in rat adipose tissue.
AB  - Studies on the biochemical and molecular mechanisms underlying obesity have shown
      that the expression of some proteins was decreased with obesity in rat adipose
      tissue. One of these proteins is carbonic anhydrase III (CA III) which
      constitutes 24% of the cytosolic protein content and its function is unclear. A
      freshly isolated rat adipose cell culture model was used to examine the effect of
      leptin and insulin on CA III expression. It was found that leptin decreased CA
      III expression while insulin increased it which suggests that the decrease in CA
      III expression observed in obesity in rat adipose tissue may be related to
      hyperleptinemia.

PMID- 15500002
TI  - Carbonic anhydrases in chick extra-embryonic structures: a role for CA in
      bicarbonate reabsorption through the chorioallantoic membrane.
AB  - The villus cavity cells, a specific cell type of the chick chorioallantoic
      membrane, express both cytosolic carbonic anhydrase in their cytoplasm and HCO3(
      )/Cl(-) anion exchangers at their basolateral membranes. By immunohistochemical
      analysis, we show here that villus cavity cells specifically react with
      antibodies directed against the membrane-associated form of carbonic anhydrase,
      CAIV. Staining is restricted to the apical cell membranes, characteristically
      invaginated toward the shell membrane, as well as to endothelia of blood vessels
      present in the mesodermal layer. The occurrence of a membrane-associated CA form
      at the apical pole of villus cavity cells, when definitively confirmed, would be
      fairly consistent with the role proposed for these cells in bicarbonate
      reabsorption from the eggshell so to prevent metabolic acidosis in the embryo
      during development.

PMID- 15500003
TI  - Redox state and carbonic anhydrase isozyme IX expression in human renal cell
      carcinoma: biochemical and morphological investigations.
AB  - Clear renal cell carcinomas (RCC) frequently express carbonic anydrase IX (CA IX)
      because of non-functional mutation of von Hippel Lindau (VHL) tumor suppressor
      gene. CA IX is a tumor-associated transmembrane antigen, which catalyzes the
      extracellular, reversible hydration of carbon dioxide to bicarbonate and proton
      and thereby contributes to acidification of extracellular milieu. Extracellular
      acidic pH facilitates tumor growth and progression. CA IX expression is
      upregulated by Hypoxia Inducible Factor-1 (HIF-1), which is negatively controlled
      by oxygen via wild type VHL protein and is also regulated by the cell redox
      state. We investigated the immunohistochemical pattern of distribution of CA IX
      in a small series (14 cases) of RCCs. CA IX expression was matched with the redox
      state of RCC, stratifying our series in relation to clinical and
      histopathological parameters, such as Fuhrman grade, staging, proliferation
      markers expression, and particularly, the presence of necrosis. Our results show
      for the first time the existence of a perivascular pattern of CA IX distribution
      in RCC. We also found a significant relationship between CA IX expression and the
      presence of necrosis. Tumors with higher CA IX expression exhibited higher degree
      of necrosis (p < 0.05). Notably, an almost significant relationship between the
      redox state and CA IX expression was detected in RCC patients with 5 years
      disease-free survival, most of them showing organ-confined disease. Tumors with
      lower redox state showed an algebraically higher degree of CA IX expression. On
      the contrary, tumors with higher redox state exhibited an algebraically lower CA
      IX expression (p = 0.057). The observed relationship of CA IX expression and
      necrosis suggests a role for CA IX in RCC. Further investigations are necessary
      to further establish the role of the redox state in regulation of CA IX
      expression in RCC.

PMID- 15500004
TI  - Adipocyte-fatty acid binding protein induces apoptosis in DU145 prostate cancer
      cells.
AB  - Adipocyte-fatty acid binding protein (A-FABP) is a 14-15 kDa cytoplasmic protein
      that binds unesterified fatty acids (FA). It is believed that A-FABP is present
      in normal cells and disappears in cancer cells. Prostate cancer DU145 cells lack
      expression of A-FABP. Here, we report that transfection of A-FABP blocked growth
      of DU145 cells suggesting its role as a tumor suppressor. A-FABP transfected-
      prostate cancer DU145 cells underwent apoptosis when induced to overexpress A
      FABP using an ecdysone-controlled expression system. DU145 cell cultures in
      complete medium exhibited a maximum of approximately 28% of apoptotic cells after
      96 h of exposure to an ecdysone analog, Ponasterone A. We found that the possible
      mechanisms leading to the observed apoptotic effect may be due, in part, to an
      overexpression of tumor necrosis factor-alpha (TNF-alpha) and a moderate
      downregulation of transforming growth factor-alpha (TGF-alpha) in DU145 cells
      overexpressing A-FABP. The epidermal growth factor receptor (EGFR)/phosphatidyl
      inositol 3-kinase (PI 3-kinase) signaling pathway was not altered in these cells,
      suggesting that A-FABP may cause apoptosis by inducing downregulation of
      essential autocrine growth factors and/or upregulation of pro-apoptotic ones.

PMID- 15500005
TI  - Fatty acid synthase as a tumor marker: its extracellular expression in human
      breast cancer.
AB  - Overexpression of fatty acid synthase (FAS EC 2.3.1.85) is associated with
      certain cancers and therefore is a putative tumor marker. The presence of FAS in
      patients with breast, prostate, colon, ovarian, and other cancers has been
      reported. The mechanism of FAS overexpression in malignancies remains unknown.
      Here, we show that FAS is released into the extracellular space in cancer cells.
      The extracellular FAS are present in various immunoreactive forms, and show
      different expression patterns in various cancer cells. In serum of breast cancer
      patients, the FAS is a small molecule similar to the form in breast cancer cell
      lysate but not conditioned medium of cultured cells. The extracellular expression
      of FAS in breast cancer cells is time dependent and may be hormone independent.
      These results indicate that the FAS are an ordered cellular response of a living
      cell and actively exclude excess intracellular FAS molecules from the cell. This
      phenomenon is up-regulated in breast and may be in other cancer cells as well.
      Significant elevation of FAS was detected in serum of breast cancer patients
      compared to healthy subjects. In comparison with CA27.29, no correlation between
      these two tumor markers was found. Thus, the extracellular FAS may serve as a
      potential diagnostic and prognostic marker.

PMID- 15500006
TI  - Screening for small molecule inhibitors of insulin-like growth factor receptor
      (IGF-1R) kinase: comparison of homogeneous time-resolved fluorescence and 33P-ATP
      plate assay formats.
AB  - Insulin-like growth factor receptor 1 (IGF-1R) plays a critical role in oncogenic
      transformation (1). IGF-1R is overexpressed in some tumors including breast,
      lung, cervical, and Wilms' tumors (2-6). Upon binding of IGF-I or IGF-II, IGF-1R,
      a tyrosine kinase, phosphorylates tyrosine residues on two major substrates, IRS
      1 and Shc, which subsequently signal through the Ras/Raf and PI 3-kinase/AKT
      pathways (7). Extensive literature has shown that when the IGF-1R signaling
      pathway is blocked by antisense, dominant negative truncation or neutralizing
      antibodies, cellular transformation and tumor formation in mice is inhibited (8
      18). Small molecule kinase inhibitors represent a valid approach to inhibit
      activity and downstream signalling of IGF-1R. To date, few potent and selective
      small molecule inhibitors of IGF-1R kinase activity have been reported. We
      expressed the tyrosine kinase domain of IGF-1R (IGF-1R/TK) in insect cells and
      subsequently purified the partially activated IGF-1R/TK. A compound library has
      been screened using a homogeneous time-resolved fluorescence (HTRF) assay. The
      hits generated by HTRF were then evaluated in a 33P ATP streptavidin-Flashplate
      assay (Flashplate). There was approximately 78% hit congruence between the two
      assay formats. One compound, C100, inhibited the IGF-1R kinase activity with an
      IC50 of 1 microM. C100 also inhibited IGF-1R autophosphorylation, AKT and MAPK
      activations in cells. This inhibitor provides a useful tool for studying IGF-1R
      in cells.

PMID- 15500007
TI  - Improving the toxicity profile of chemotherapy for advanced ovarian cancer: a
      potential role for CT-2103.
AB  - Significant progress has been made in the management of advanced ovarian cancer.
      Response rates to platinum-based chemotherapy are respectable; however,
      recurrence continues to be the rule rather than the exception. Chemotherapy is
      administered as initial treatment and for disease recurrence, often over a period
      of many years--thus ovarian cancer is considered a chronic disease by many
      oncologists. The importance of the taxanes in the treatment of ovarian cancer is
      well established. However, taxanes are associated with numerous toxicities,
      resulting in the need for alternative dosing strategies that produce fewer side
      effects, or the discovery of novel taxanes with equivalent anti-tumor activity,
      but a more favorable toxicity profile. Several taxanes are in development
      including CT-2103, a macromolecule consisting of paclitaxel conjugated to a
      biodegradable, water-soluble polymer of glutamic acid. Clinical data of CT-2103
      as a single agent and in combination have demonstrated activity in previously
      treated ovarian cancer patients, both in platinum-sensitive and platinum
      resistant disease. CT-2103 appears to be potentially associated with a more
      favorable toxicity profile relative to paclitaxel, and enhanced solubility allows
      for a 10-minute infusion. Ongoing trials employing this agent will focus on
      extending survival, optimizing quality of life, and defining a possible role for
      CT-2103 in the standard management of advanced ovarian cancer.

PMID- 15500008
TI  - Berberine sensitizes human glioma cells, but not normal glial cells, to ionizing
      radiation in vitro.
AB  - The identification of nontoxic agents that can enhance the efficacy of
      postoperative radiotherapy for patients with glioblastoma multiforme (GBM)
      remains a challenge in oncology. We evaluated human GBM cell lines for their
      responsiveness to berberine, an alkaloid compound used commonly in Asia as an
      antibiotic. In experiments measuring clonogenic survival, treatment with a
      nontoxic dose of berberine rendered GBM cells more sensitive than vehicle-treated
      control cells to x-rays. Such radiosensitization was not observed in parallel
      experiments with primary human glial cultures. These data suggest that berberine
      could be integrated with postoperative radiotherapy to selectively promote
      residual GBM tumor cell death

PMID- 15500009
TI  - Ex vivo therapeutic index by drug sensitivity assay using fresh human normal and
      tumor cells.
AB  - Toxicity is a major deterrent to achieving substantial improvements in cancer
      management, since most anticancer drugs inadequately distinguish normal and
      neoplastic tissues. Improving the differential between beneficial and toxic
      effects of therapy--therapeutic index--is a major clinical objective, but
      therapeutic index for cytotoxic drugs is narrow. Fresh tumor and normal cells
      from 59 patients with acute myeloid leukemia, non-Hodgkin's lymphoma, ovarian
      cancer and cancers of unknown origin were tested for ex vivo drug sensitivity
      using apoptosis by morphology assays. Drugs tested included carboplatin,
      doxorubicin, vincristine, cytarabine, fludarabine, mafosfamide and etoposide.
      Therapeutic index was derived from the ratio of normal and tumor cell LC90s.
      Individual patient therapeutic index varied markedly for different drugs and drug
      therapeutic index varied from patient to patient ranging from extremely
      unfavourable (<0.001) through excellent (>1000) reflecting patient heterogeneity.
      Therapeutic index for each drug was consistent with clinical expectations.
      Significantly, there was no relationship between normal and tumor cell LC90s. We
      conclude that further laboratory and clinical evaluation is required but the
      derived ex vivo therapeutic index could enhance choice of chemotherapy by
      reducing toxicity and/or improving efficacy.

PMID- 15500010
TI  - Genomic-wide cDNA microarray screening to correlate gene expression profile with
      chemoresistance in patients with advanced lung cancer.
AB  - We conducted a study using cDNA microarray analysis to determine whether
      expression levels of genes in tumors were correlated with tumor response to
      chemotherapy. Between September 2000 and December 2001, 47 patients were
      registered in the study. Eighteen patients had small cell lung cancer (SCLC), and
      others had non-small cell lung cancer (NSCLC). All patients except three received
      platinum-based chemotherapy. Sixteen of the 18 patients with SCLC (89%) and 13 of
      the 29 patients with NSCLC (45%) responded to chemotherapy, respectively.
      Transbroncheal biopsy specimens of tumors were obtained before chemotherapy. The
      expression levels of 1176 genes in tumor specimens were analyzed using the Atlas
      Human Cancer 1.2 Array. When we analyzed the data for correlations between gene
      expression levels and tumor response to chemotherapy, there was a significant
      increase in the expression of nine genes in non-responders compared with
      responders to chemotherapy (p< 0.01). Multivariate regression analysis revealed
      that allogenic inflammatory factor, HLA-DR antigen associated invariant subunit
      and MHC class II HLA-DR-beta precursor were independent chemo-resistant factors
      (p<0.0001). When we analyzed the differences in gene expression levels between
      patients with SCLC and NSCLC, expression levels of one or more resistant genes
      were increased in comparison with the mean expression of control house keeping
      genes in five of 18 SCLC patients and 19 of 29 NSCLC patients, respectively
      (p=0.012). In conclusion, some chemo-resistant genes were detected in the tumor
      tissue of lung cancer patients using cDNA microarray analysis. A prospective
      study is required to confirm whether expression levels of these genes reflect
      chemosensitivity.

PMID- 15500011
TI  - Targeting K+ channels for cancer therapy.
AB  - A number of experimental evidences in cellular biology and pharmacology
      demonstrate that K+ channels are involved in the regulatory mechanisms of
      neoplastic cell proliferation and survival. Among the various types of K+
      channels known so far, those that express an inwardly rectifying current (mainly
      the types named Kir, EAG and HERG) appear of peculiar importance in favoring
      cancer progression in vivo. In fact, besides helping to maintain a constantly
      depolarized value of the resting potential required for deregulated tumor growth,
      they can confer selective advantages to cancer cells in an hypoxic
      microenvironment, such as that of tumor masses. Inhibitors and modulators of K+
      channels have been demonstrated to have the ability to impair cancer cell
      proliferation in vitro and to counteract cancer progression in vivo. A process of
      rigorous scientific verification at a pre-clinical level of the anticancer
      potential of K+ channels inhibitors and modulators have never been rationally
      performed thus far, but would appear opportune in the light of the data here
      discussed.

PMID- 15500012
TI  - CPI-0004Na, a new doxorubicin prodrug, reduces growth of 3LL-H61 carcinoma lung
      metastases in C57BI/6 mice.
AB  - The ETAP concept (Extracellularly Tumor-Activated Prodrug) is a new approach
      developed to overcome the lack of selectivity and the side effects responsible
      for the limited efficacy of chemotherapeutic agents. CPI-0004Na, a doxorubicin
      (Dox) prototype prodrug of this type, is less toxic than free Dox and showed
      increased efficacy against subcutaneous human tumor xenografts. The aim of this
      study was to assess the efficacy of the prodrug vs Dox (given ip) at their
      maximal tolerated dose (MTD) for this administration schedule (129.3 micromol/kg
      and 12.93 micromol/kg, respectively) against experimentally induced 3LL-H61
      carcinoma lung metastases in mice. Our results indicate that, Dox has no effect
      on the number of lung metastases while CPI-0004Na induces a 38.3% reduction on
      average. When considering the effect on the proportion of the lungs' surface
      covered by metastases, Dox induces a 39% reduction while the prodrug CPI-0004Na
      is about two fold more active with a 71% decrease.

PMID- 15500014
TI  - Information storage for health-care providers: it's not as simple as it seems.
AB  - As medical practices migrate from paper to computers for record keeping, new
      issues surrounding the safe storage of such data are arising. These range from
      choosing an electronic storage format to ensuring that any electronic information
      stored today will be available and readable years into the future. Privacy and
      security issues also continue to be important, especially since the HIPAA
      regulations were instituted. With the rapid advances in technology, finding the
      right solution may be like trying to hit a moving target, yet some basic
      principles, outlined in this article, should make this difficult task easier.

PMID- 15500013
TI  - President Reagan's legacy.

PMID- 15500015
TI  - Internet patient scheduling in real-life practice.
AB  - Scheduling patients for busy clinical practices has been an inefficient, time
      consuming, and expensive process. This article relates the experience of a large
      primary-care group in adopting sheduling by the Internet. This has resulted in
      improved scheduling, economies in staffing, and greater patient satisaction. An
      added bonus has been the reduction of failed appointments.

PMID- 15500016
TI  - Online consultations: new entry portals.

PMID- 15500017
TI  - Best practices in record completion.
AB  - Completion of hospital and office (clinic) medical records is one of the least
      popular of clinicians' duties. Adherence to Joint Commission on Accreditation of
      Healthcare Organizations (JCAHO) requirements and submission of hospital and
      provider bills to insurers and patients, however, are predicated on patient
      charts being completed and signed in a timely manner. This article details the
      rules and regulations that many institutions impose on providers to assure that
      records are up to date. It also discusses the carrot-and-stick approaches that
      are frequently used to assure compliance.

PMID- 15500018
TI  - Communicating with limited English proficiency (LEP) patients: question of health
      care access.
AB  - In the United States, the ability to understand English plays an essential role
      in how well patients and health-care providers communicate. This article
      highlights the concerns of providers, differential health-care outcomes, and risk
      management concerns of providing health care in an increasingly diverse and
      polyglot population.

PMID- 15500019
TI  - Stealth downcoding and what you can do about it.

PMID- 15500020
TI  - How to make the CBO model work for you.

PMID- 15500021
TI  - Keeping internal chart reviews from being used against you: 11 useful strategies.
AB  - Internal chart reviews are useful tools for practices to determine the accuracy
      of their coding when billing for services, especially to governmental payers.
      They can also boomerang, however, and be used as evidence against a practice when
      their results are not fully understood or implemented. This article provides some
      guidance to help practitioners realize the fuller value of chart reviews in terms
      of over- and under-coding, adequacy of documentation, and attorney-client
      privilege.

PMID- 15500022
TI  - Physician leadership: a roadmap for health-system change.
AB  - Physician involvement in health-system decision making and their support of
      health-system initiatives can be critical to a health system's success. Many
      physicians, however, do not have the business skills or perspective to be
      effective contributors. This paper identifies three levels of physician leader
      development: awareness and head knowledge; creating an "us" culture; and taking
      ownership of the marketplace. It also identifies three physician leader
      development methods that health systems can use to reach these points: integrated
      executive education; project-based learning; and facilitating ownership. Based on
      health-system objectives, top management should choose an appropriate level of
      physician leader development and then implement an appropriate change plan by
      using the proposed physician leader-development methods.

PMID- 15500023
TI  - Finding suitable applicants for a staff opening.
AB  - Many medical practices run classified ads to seek applicants for job openings and
      do little else. Several effective recruitment strategies, however, can be used in
      addition to or instead of classified advertising. In this article, the author
      suggests working both inside and outside the practice to draw in top-notch job
      applicants. She describes how local schools, employment agencies, and temporary
      agencies can help fill positions in medical practices and how such arrangements
      typically work. The author also suggests ways to bring excellent former employees
      back to the fold. Finally, she offers practical tips for protecing yourself
      financially when hiring a new employee through an agency and paying a placement
      fee.

PMID- 15500024
TI  - Medical malpractice litigation raises health-care cost, reduces access, and
      lowers quality of care.
AB  - This article examines the impact of medical malpractice litigation on health-care
      cost, the availability of employer-sponsored health insurance, and the quality of
      health-care services. Among the findings are that unlimited, uncapped medical
      malpractice litigation added as much as 97.5 billion dollars annually to the cost
      of hospital and physician services; increased the annual cost of employer
      provided health insurance by as much as 12.7 percent; decreased by 2.7 million
      the number of workers and their families covered by employer-provided health
      insurance; caused a 6 percent decline in physicians in the U.S., many of whom
      work in critical specialty areas; lost access to critical medical services for up
      to 14.4 million people; resulted in malpractice underwriting losses of 8.6
      billion dollars in 2001, double that of 10 years earlier; and had a low
      predictive value in identifying whether medical malpractice had occurred.

PMID- 15500025
TI  - U.S. Supreme Court clarifies that owner-employees are protected by ERISA.

PMID- 15500026
TI  - The courts look at professional advertising.

PMID- 15500027
TI  - The perception of four basic emotions in human and nonhuman faces by children
      with autism and other developmental disabilities.
AB  - Children who experienced autism, mental retardation, and language disorders; and,
      children in a clinical control group were shown photographs of human female,
      orangutan, and canine (boxer) faces expressing happiness, sadness, anger,
      surprise and a neutral expression. For each species of faces, children were asked
      to identify the happy, sad, angry, or surprised expressions. In Experiment 1,
      error patterns suggested that children who experienced autism were attending to
      features of the lower face when making judgements about emotional expressions.
      Experiment 2 supported this impression. When recognizing facial emotion, children
      without autism performed better when viewing the full face, compared to the upper
      and lower face alone. Children with autism performed no better when viewing the
      full face than they did when viewing partial faces; and, performed no better than
      chance when viewing the upper face alone. The results are discussed with respect
      to differences in the manner that children with and without autism process social
      information communicated by the face.

PMID- 15500029
TI  - The relation between sluggish cognitive tempo and DSM-IV ADHD.
AB  - To test the relation between sluggish cognitive tempo (SCT) and DSM-IV ADHD
      symptoms, parent and teacher ratings of the 18 DSM-IV ADHD items and five
      potential SCT items were obtained in a community sample of 8-18 year-old twins
      that was overselected for ADHD and learning disabilities (n = 296). Confirmatory
      factor analyses revealed that a three-factor model provided the best fit to the
      data for both parent and teacher ratings. DSM-IV inattention and hyperactivity
      impulsivity symptoms loaded on two factors consistent with the DSM-IV model, and
      five SCT symptoms loaded primarily on a third factor. The SCT and inattention
      factors were highly correlated, whereas SCT and hyperactivity-impulsivity were
      weakly related. Both raters indicated that children meeting symptom criteria for
      the combined and inattentive subtypes exhibited significantly more SCT symptoms
      than those meeting symptom criteria for hyperactive-impulsive type and the
      comparison group without ADHD. Children meeting symptom criteria for the
      inattentive type exhibited significantly more SCT symptoms than those meeting
      criteria for the combined type, based on teacher ratings. These results suggest
      that SCT is an internally consistent construct that is significantly associated
      with DSM-IV inattention.

PMID- 15500028
TI  - Time perception: does it distinguish ADHD and RD children in a clinical sample?
AB  - This study used a double-dissociation design to evaluate whether children with
      ADHD demonstrated specific deficits relative to children with Reading Disorders.
      Recent theory suggests that ADHD children have deficits in time perception and
      working memory, whereas RD children have deficits in phonological decoding. The
      performance of 113 clinic-referred children aged 6-11 was examined using measures
      of working memory, phonological processing, and time perception. Respondents
      completed two time production tasks in which they were to judge when 30-s had
      elapsed, and another in which they were asked to estimate the duration of the
      Conners' CPT (CCPT). Time Perception and phonological processing variables were
      submitted to a 2 x 2 ANCOVA (ADHD vs. RD), covarying for age, SES, IQ, and
      working memory. Children with ADHD were more likely to overestimate the time
      taken for the CCPT than children without ADHD, but no group differences were
      found on the 30-s estimation tasks. Children with RD did not display deficits in
      time estimation, but showed deficits in auditory phonological processing. The
      lack of interaction effects supported an "etiological subtype" over the
      "phenocopy" model of ADHD and RD. No group differences were detected using the
      CCPT. Although our previous studies did not find an order effect for the Conners'
      CPT in a 1-hr battery, a fatigue effect was evident with a 1.5-hr battery. The
      implications for Barkley's behavioral inhibition theories (R. Barkley, 1997) are
      discussed.

PMID- 15500030
TI  - Negative emotions and alcohol use initiation in high-risk boys: the moderating
      effect of good inhibitory control.
AB  - Studies on the relation between negative affect and later alcohol use have
      provided mixed results. Because definitions of negative affect often include
      diverse emotions, researchers have begun to dismantle this higher-order construct
      in an attempt to explain these inconsistent findings. More recent evidence also
      indicates that good inhibitory control may moderate the relation between negative
      emotions and alcohol use. The current longitudinal investigation examined the
      independent relation between three components of negative affect (i.e., depressed
      mood, fear, and anger) and alcohol use initiation in a sample of aggressive boys.
      The moderating effect of good inhibitory control was also examined. Results
      indicated that increased anger and decreased fearfulness are associated with an
      increased risk for alcohol use initiation only for boys with moderate to low
      levels of inhibitory control. However, depressed mood predicted alcohol use
      initiation for boys with good inhibitory control. The potential implications for
      substance use prevention efforts are discussed.

PMID- 15500031
TI  - The relationship between parental alcoholism and adolescent psychopathology: a
      systematic examination of parental comorbid psychopathology.
AB  - The relationship between parental alcohol dependence (with and without comorbid
      psychopathology) and adolescent psychopathology was examined in a sample of 665
      13-17 year-old adolescents and their parents. Results indicated that adolescents
      who had parents diagnosed with alcohol dependence only did not significantly
      differ from adolescents who had parents with no psychopathology in regard to any
      of the measures of psychological symptomatology (substance use, conduct disorder,
      and depression) or clinical diagnoses (alcohol dependence, marijuana dependence,
      conduct disorder, or depression) assessed. In contrast, adolescents who had
      parents diagnosed with alcohol dependence and either comorbid drug dependence or
      depression were more likely to exhibit higher levels of psychological
      symptomatology. In addition, adolescents who had parents diagnosed with alcohol
      dependence, depression, and drug dependence were most likely to exhibit
      psychological problems. These findings underscore the importance of considering
      parental comorbid psychopathology when examining the relationship between
      parental alcoholism and offspring adjustment.

PMID- 15500032
TI  - Psychopathic traits in boys with and without attention-deficit/hyperactivity
      disorder: concurrent and longitudinal correlates.
AB  - To investigate the role of psychopathic traits in a clinical and comparison
      sample, we obtained dimensional California Child Q-Set (CCQ) personality profiles
      for 66 preadolescent boys with attention-deficit/hyperactivity disorder (ADHD)
      and 56 comparison boys during naturalistic summer programs and correlated each
      boy's CCQ profile with an expert-derived CCQ psychopathy prototype. These scores,
      representing each boy's degree of similarity to the prototype, were significantly
      associated with concurrent externalizing diagnoses and symptoms and, with
      statistical control of these externalizing features, concurrent measures of
      objectively observed noncompliance, overt and covert antisocial behavior, and
      peer sociometric nominations indexing peer rejection. Psychopathic traits were
      not associated with peer acceptance. CCQ psychopathy dimension scores also
      predicted severity of delinquency at a 5-7-year prospective follow-up, with
      statistical control of age, baseline externalizing diagnoses and symptoms, and
      baseline objective observations of antisocial behavior. Predictions held when
      overt behavioral items from the CCQ, which may have overlapped with the
      delinquency outcome criterion, were eliminated. Despite these strong effects, a
      plethora of false positives were evident in the prospective predictions to
      delinquency status. We discuss research and clinical implications of measuring
      psychopathic traits in childhood.

PMID- 15500033
TI  - Effect of children's perceived rejection on physical aggression.
AB  - This study investigated whether the perception of self as socially rejected might
      contribute to increased physical aggression among elementary-school children. It
      was hypothesized that physically aggressive children would become more physically
      aggressive over time if they perceived that they were rejected and tended to
      blame peers for social failure experiences. Third-grade boys and girls (n = 941)
      were assessed in the Fall and Spring of the school year. Peer-report data on
      physical aggression and social preference were collected, along with self-report
      data on perceived rejection and attributions for social failure experiences.
      Results for boys were consistent with hypotheses, whereas the results for girls
      revealed a different pattern of relations. These results constitute prospective
      evidence that children's self-perceptions of social rejection can uniquely
      influence externalizing behavior. Results are discussed in terms of mechanisms
      that might mediate the relation between perceived rejection and physical
      aggression.

PMID- 15500034
TI  - Significance of childhood conduct problems to later development of conduct
      disorder among children with ADHD: a prospective follow-up study.
AB  - This study investigates whether low to moderate levels of childhood oppositional
      defiant disorder (ODD) and conduct disorder (CD) behaviors contribute to the
      development of clinically diagnosed CD in adolescence, in children with attention
      deficit hyperactivity disorder (ADHD). Participants were 207 White boys (ages 6
      12) with ADHD free of conduct disorder diagnoses. Parent and teacher ratings were
      obtained. Participants were assessed at mean age 18 by clinicians blind to
      childhood status. A non-ADHD group (recruited in adolescence) was also studied.
      ODD behavior ratings did not predict CD in adolescence, whereas CD behavior
      ratings did. No single ODD or CD behavior predicted adolescent outcome. ADHD
      probands with very low ratings (Not at all, Just a little) by parents and
      teachers on all CD behaviors were still at significantly increased risk for CD in
      adolescence, compared to non-ADHD controls. The same relationships were found
      between childhood ODD and CD behaviors, and antisocial personality disorder in
      adulthood (mean age, 25). We conclude that childhood ADHD is a developmental
      precursor of later antisocial disorder, even in the absence of comorbid ODD or CD
      in childhood. However, low levels of CD-type problems are not innocuous, because
      they predict later CD among children with ADHD without comorbid CD.

PMID- 15500035
TI  - [Stress-induced alteration of the antiaggressive effect of anxiolytics].
AB  - The influence of stresses of various etiology (prolonged isolation, inescapable
      electrostimulation) on the antiaggressive effect of anxiolytics was studied in
      outbread white male rats. It was established that, in contrast to the
      anticonflict effect (decreasing under the action of stress), then antiaggressive
      action of the drugs studied (diazepam, phenazepam, clonazepam, alprazolam)
      exhibits qualitative changes. In the absence of stress, the threshold of
      aggressive reaction is low and anxiolytics increase this level. Under the action
      of stress, the threshold of aggressive reaction increases, and the same drugs
      reduce this threshold to the normal level, thus producing proaggressive action.
      The degree of changes and the rate of restoration of the initial activity depend
      on the efficacy of anxiolytics, the strength and duration of stress, and on the
      duration of drug administration during the stress aftereffect. A possible
      mechanism of this phenomenon can be the interaction of the GABA-benzodiazepine
      and opiate endogenous systems.

PMID- 15500036
TI  - [Ladasten induces the expression of genes regulating dopamine biosynthesis in
      various structures of rat brain].
AB  - The effect of ladasten (50 mg/kg) on the activity of tyrosine hydrolase (TH) and
      DOPA-decarboxylase (DDC) gene expression and on the content of dopamine and L
      DOPA in the striatum and hypothalamus in rat brain was studied depending on the
      duration of drug action. In the initial stage (first hours) of the drug action,
      the dopaminergic effects are related to an increase in the dopamine release. The
      observed accumulation of L-DOPA and dopamine is correlated with the transcription
      activity of genes studied. This leads to a conclusion that the pharmacological
      activity of ladasten is related to activation of de novo synthesis of TH and DDC.
      There is a certain difference in the ladasten action upon the TH and DDC gene
      expression of the key enzymes in hypothalamus and striatum of rat brain.

PMID- 15500037
TI  - [Neuroactivating mechanism of action of the new trophinotropic drug cerebral].
AB  - The new drug cerebral, as well as its low-molecular-weight (LMW) fraction (MW, <
      or = 500 Da) separated from a ready-to-use commercial form of this new
      neutrotropic drug, increases the level of synthesis and secretion of the nerve
      growth factor (NGF) in rats under conditions of experimental hemorrhagic stroke
      (HS), while not influencing the NGF synthesis and secretion in intact animals.
      This neuroactivating effect of the trophinotropic drug cerebral and its LMW
      fraction in the acute HS development stage was observed upon intranasal
      administration. In comparison with parenteral (intraperitoneal) administration,
      the intranasal introduction provides for the optimum drug delivery to the CNS
      bypassing the blood-brain barrier. Trophinotropic agents are a new class of drugs
      with neuroactivating mechanism of action upon the NGF synthesis and secretion
      under HS conditions.

PMID- 15500038
TI  - [Antiischemic and antiarrhythmic effect of esafosfina].
AB  - Esafosfina, a new preparation based on fructose 1,6-diphosphate, supported the
      pumping ability of the heart in experiments with a 40-min occlusion followed by
      60-min reperfusion of the anterior descending branch of the left coronary artery
      in anesthetized cats. Esafosfina also exhibited a pronounced antifibrillatory and
      antiarrhythmic action in anesthetized rats with ventricular fibrillation model.

PMID- 15500039
TI  - [The effect of esafosfina on cerebral circulation in intact and ischemized rat
      brain].
AB  - The physiological metabolite esafosfina (fructose 1,6-diphosphate) influences the
      cerebral circulation of intact male rats. Injected intravenously in a dose of 250
      mg/kg, esafosfina improved both the blood supply to brain and the local blood
      flow in the parietal region. Under the conditions of global transient cerebral
      ischemia, the cerebrovascular effect of the drug tends to increase. Esafosfina
      produced dissimilar changes in the arterial blood level, which could be explained
      by various basic status of the test animals. The pronounced cerebrovascular
      activity of esafosfina plays a key role in its neuroprotector effect.

PMID- 15500040
TI  - [The effect of dalargin and des-Tyr-dalargin on the functional state of intact
      and ischemized-reperfused myocardium].
AB  - Experiments on isolated perfused rat heart showed that dalargin, an antagonist of
      mu- and delta-opioid receptors, favors a decrease in the parameters of
      contractility of intact myocardium, while not influencing the pumping function
      (systolic and diastolic contractility) of reperfused myocardium. At the same
      time, des-Tyr-dalargin (the non-opioid analog of dalargin) suppresses the
      contractility of both the intact heart and the isolated myocardium subjected to
      global ischemia and reperfusion. Both dalargin and des-Tyr-dalargin reduced the
      incidence of reperfusion-induced arrhythmia, but did not affect the coronary flow
      before ischemia and after restoration of the coronary flow. It is suggested that
      the effect of dalargin is related to activation of the cardiac delta-opioid
      receptors, while the inotropic action of des-Tyr-dalargin involves other receptor
      mechanisms.

PMID- 15500041
TI  - [Antiarrhythmic properties of 2-(2'-hydroxy-2')-substituted ethyl-1,2,3,4
      octahydropyrrolo[1,2-a]pyrazines].
AB  - The antiarrhythmic activity and acute toxicity of a series of 2-(2'-hydroxy-2')
      substituted ethyloctahydropyrrolo[1,2-a]pyrazines were studied. Two most
      promising compound (PV-238) is characterized by high antiarrhythmic activity,
      broad spectrum of action, and low toxicity.

PMID- 15500042
TI  - [The effect of a potential drug ingamine on a model of noninfectious pneumonia].
AB  - The potential drug ingamine (glutarylhistamine) showed pronounced anti
      inflammatory activity on a model of acute noninfectious pneumonia and in the
      stage of chronic inflammation induced by singe instillation of Sephadex (5 mg/kg)
      in Wistar rats. A 6-day treatment with ingamine (50-500 microg/kg) by inhalation,
      intragastric, and intraperitoneal administration produced an anti-inflammatory
      effect (expressed to various degrees), which was manifested by a decrease in
      alveolitis, bronchitis, obstructive emphysema, lymphocyte-neutrophile
      infiltration of interalveolar septa, cytosis, and neutrophile component of
      bronchoalveolar lavage and by normalization of the cytogram. The most pronounced
      effect was observed upon inhalation in a dose of 500 microg/kg. In the stage of
      chronic inflammation, the inhalation of ingamine in a dose of 500 microg/kg
      produced a significant antiinflammatory action for both 10- and 20-day treatment.
      The effect was comparable with that of the inhaled glucocorticoid budesonide.

PMID- 15500043
TI  - [The effect of hepatoprotectors containing phospholipids on rats with
      experimental acute pancreatitis].
AB  - The experiments on rats with a model acute pancreatitis showed that
      hepatoprotectors containing phospholipids (eplir and essentiale) improve the
      parameters of metabolism and the functions and histological characteristics of
      the pancreas and liver. Both drugs produced an antioxidant effect, decreased the
      activity of alpha-amylase, lipase, enzymes of hepatic origin in the blood, and
      reduced the content of creatinine, glucose, urea, bilirubin, and lipids. The
      therapeutic action of eplir was more pronounced than that of essentiale.

PMID- 15500045
TI  - [The effect of melatonin on platelet hemostasis in rats with traumatic disease].
AB  - The experiments on rats with model traumatic disease showed that melatonin
      administration produces a dose-dependent positive effect, decreasing the degree
      and duration of disturbances in platelet hemostasis.

PMID- 15500044
TI  - [The protective effect of alpha-tocopherol characterized by erythron system
      indices in rats with chronic nitrite intoxication].
AB  - The effect of alpha-tocopherol administered in a dose of 15 and 150 mg/kg on the
      erythron system was studied in rats subjected to chronic nitrite intoxication.
      The chronic poisoning with sodium nitrite led to three-phase changes in the
      concentration of erythrocytes (RBC count) and hemoglobin and to activation of the
      erythropoiesis and erythrophagocytosis processes. The introduction of alpha
      tocopherol on the background of intoxication with sodium nitrite prevents from
      the development of erythropenia, causes erythrocytosis (in large doses),
      decreases the degree of cytoarchitectonic changes, and reduces the erythropoiesis
      and erythrophagocytosis activity.

PMID- 15500046
TI  - [6,8-Dimethyl-2-piperidinomethyl-2,3-dihydrothiazolo[2,3-f]xanthine: a new
      inductor of the monooxygenase system inhibits experimental intrahepatic
      cholestasis in rats].
AB  - 6,8-Dimethyl-2-piperidinomethyl-2,3-dihydrothiazolo[2,3-f]xanthine, a new
      inductor of the monooxygenase system, inhibited the development of experimental
      intrahepatic cholestasis induced by alpha-naphthylisothiocyanate in rats. The
      drug stimulated the detoxicating function of liver, increased the survivability
      of rats, restored the level of microsomal protein and cytochrome P-450, decreased
      the cell-average erythrocyte fragility, and reduced the activity of cholestasis
      markers and the amount of TBA-active products in hepatocytes.

PMID- 15500047
TI  - [The effect of mexidol on the process of glycolysis in rats under acute stress
      conditions].
AB  - Pretreatment with mexidol (100 mg/kg) protected white male rats (n = 29) under
      the conditions of acute (3 h) immobilization stress. This was evidenced by
      monitoring of the levels of glucose, pyruvic, and lactic acid in the rat brain,
      liver, spleen, thymus, and blood serum. In both brain and peripheral organs,
      mexidol the shifted the equilibrium toward pyruvate--an energetically more
      favorable substrate of enzymatic oxidation.

PMID- 15500048
TI  - [Hepatoprotectors containing phospholipids decrease the immunosuppressive effect
      of prednisolone in rats with experimental toxic hepatitis].
AB  - The experiments on rats with a model toxic hepatitis induced by
      tetrachloromethane showed that hepatoprotectors containing phospholipids (eplir
      and essentiale) introduced in combination with prednisolone decrease the
      immunodepressant effect of this glucocorticoid, as manifested by a decrease in
      the atrophy of thymus and an increase in the amount of blood lymphocytes, the
      number of splenic blasts, and the functional activity of mononuclear cells in C3b
      and Fc(gamma) receptors in peritoneal exudate.

PMID- 15500049
TI  - [Antitumor activity of the new gestagen 17alpha-acetoxy-3beta-butanoyloxy-6
      methyl-pregna-4,6-dien-20-one].
AB  - Antitumor activity of a new highly active promising gestagen 17alpha-acetoxy
      3beta-butanoyloxy-6-methyl-pregna-4,6-dien-20-one (butagest) was studied in mice
      with model cervical carcinoma (RShM-5). The reference drug was medroxyprogesteron
      acetate (MPA, Depo Provera) used in clinics. The new preparation introduced
      perorally in a dose of 1 mg per mice inhibited the model tumor growth by 73%,
      which was 18% (p < 0.01) more effective than the action of the reference drug
      MPA. The effect of the new gestagen was also studied in vitro with respect to
      human breast carcinoma of the MCF-7 line and human cervical carcinoma HeLa. The
      viability of the tumor cells was studied during a 6-day incubation with the drug
      at a concentration of 10(-7)-10(-5) M (MTT test). The reference compounds were
      progesterone and MPA. These drugs suppressed the growth of both MCF-7 and, in
      higher concentrations, of HeLa. Butagest inhibited the growth of HeLa in all
      concentrations. Thus, the new gestagen 17alpha-acetoxy-3beta-butanoyloxy-6-methyl
      pregna-4,6-dien-20-one is capable of suppressing the viability of human breast
      carcinoma and human cervical carcinoma, being comparable or even more effective
      than the reference drugs.

PMID- 15500051
TI  - [Carcinogen activity of the new drug thymodepressin studied in chronic tests on
      rats and mice].
AB  - The new drug thymodepressin was subcutaneously injected in doses 0.0145 and 0.145
      mg/kg in rats and mice over a period of 104 weeks. No statistically significant
      difference in the tumor frequencies between the test and control groups was
      observed during this period of time. It is concluded that thymodepressin is not
      carcinogenic.

PMID- 15500050
TI  - [Pharmacokinetics of glyprolines (PGP) upon intragastric administration].
AB  - The pharmacokinetics of glyprolines upon intragastric administration in rats was
      studied by monitoring the content of tritium-labeled PGP in the blood plasma and
      protein, in organs (for 5 h), and urine (for 8 h). The maximum radioactivity
      (2.25% of the introduced level) in the blood plasma was observed 15 min after
      administration of [3H]-PGP. Then, the radioactivity level gradually decreased,
      but even in 5 h it exceeded 1%. In contrast, the radioactivity of deposited
      protein gradually increased. The content of labeled PGP and its metabolites in
      organs was much lower than in the blood. The radioactivity 15 min after
      administration was as follows (%): intestine, 1.4; stomach, 0.1; liver, 0.09;
      brain, heart, and kidney, < 0.05; in 5 h, the radioactivity level was below 0.02%
      (except for intestine, where it was still greater than 0.1%). No labeled PGP or
      its metabolites were found in the urine during the 8-h period of observations. It
      is not excluded that glyprolines introduced with PGP are involved in the
      synthesis of new peptides and proteins, including collagen.

PMID- 15500052
TI  - [Improvement of light and color perception in humans upon prolonged
      administration of eleutherococcus].
AB  - The chronic administration of a liquid eleuterococcus extract significantly
      improves light and color perception in healthy humans. Significant positive
      changes in eye sensitivity were observed in both morning and evening hours.

PMID- 15500053
TI  - [Ultrasonographic evaluation of the venous tone in humans in the clinical
      pharmacology of venotropic drugs].
AB  - A new ultrasonographic method of evaluation of the venous tone in humans is
      described and experimentally justified. The method is based on the principles of
      venous occlusion plethysmograhy and ultrasonographic two-dimensional imaging of
      the cross section of cubital veins. It is found that an increment of the cross
      sectional area of the vein is correlated with a change in the volume of distal
      segment of the upper extremity according to the data of aqueous plethysmography.
      The tests with nitroglycerin and dihydroergotamine (vasoactive drugs producing
      opposite effects upon the venous tone) confirmed the possibility of using this
      technique in the clinical pharmacology of venotropic drugs.

PMID- 15500054
TI  - [On the role of GABA in anxiety and depression].
AB  - Data on the role of gamma-aminobutyric acid (GABA) in pathogenesis of anxiety and
      depression are critically assessed. Clinical and experimental results indicative
      of an important role of GABA as the neurotransmitter involved in these mental
      states and their integration within a common pathogenic process are considered.
      The general neurochemical, pharmacological, and neurophysiological aspects of
      anxiety and depression are analyzed in the context of GABAergic system
      involvement in this process and the possibility of using GABAergic agents for the
      therapy of various related disorders.

PMID- 15500055
TI  - [New prospects of using milk thistle (Silybum marianum) preparations].
AB  - Well-known and newfound properties of milk thistle (Silybum marianum)
      preparations are considered (including hepatoprotector, immunostimulant,
      antiproliferative, antisclerotic, etc.) and the ways of their realization are
      analyzed. Good prospects of further development of the drugs based on this
      medicinal plant are emphasized and the possibilities of wider clinical use are
      discussed.

PMID- 15500056
TI  - I have had enough!
AB  - I apologize for making some of you nervous, and perhaps even resentful, but I
      HAVE HAD ENOUGH! I do not like the new unethical face of my profession, where
      incessant seeking of more money has replaced service to the public, honesty, and
      self-respect. Numerous areas of major ethical concern in dentistry are identified
      in this article. The ongoing, if not accelerating, degeneration of professional
      ethics in dentistry is clearly evident to even casual observers. Improvements in
      professional ethics are necessary to regain our self-respect and the respect of
      the people we serve. All of us need to improve, including practitioners,
      speakers, dental schools accomplishing research, manufacturers, editors, and
      evaluating groups. It is time to return to honesty and to dealing with our fellow
      men and women in the way we would want to be treated ourselves. I do not think it
      is too late.

PMID- 15500057
TI  - In-office bleaching.

PMID- 15500058
TI  - Selecting nanotechnology-based composites using colorimetric and visual analysis
      for the restoration of anterior dentition: a case report.
AB  - Currently it is possible to use direct composites and layering techniques to
      replicate the complex internal structures, visible shape, color, and surface
      anatomy of natural teeth. To do so, however, requires dentists to understand the
      principles of nature and the science of dental materials to determine the most
      suitable restorative material for a specific indication. By incorporating
      relatively new technologies--colorimetric analysis, which provides computerized
      shade guide definitions of a tooth and essential information to verify shade
      mapping, and a new nanotechnology-based direct composite--into composite layering
      techniques, dentists can more predictably replicate the esthetics of natural
      teeth. This article presents a case in which both technologies, used in
      combination with a composite layering technique, contributed to the esthetic and
      functional restoration of the maxillary central incisors.

PMID- 15500059
TI  - Multidisciplinary approach in the treatment of a patient with cleft lip and
      palate: a case report.
AB  - Treatment of the patient with cleft lip and palate represents a real problem from
      both functional and esthetic points of view. Today a functional result is not
      enough. An esthetic result is both necessary and possible to improve the quality
      of life. The direct placement of an implant in the grafted alveolar cleft is not
      the ideal choice. Using a rational, multidisciplinary approach, it is possible to
      obtain esthetic results in these patients. In our case study, a 17-year-old
      patient previously treated for a unilateral cleft lip and palate and agenesis of
      the right lateral incisor was given an osseointegrated implant. Computer-assisted
      dental design (Procera CAD/CAM software, Nobel Biocare AB, Gothenburg, Sweden)
      was used for the prosthetic rehabilitation, and the end of growth was determined
      prior to placing the implant. No sign of failure or mobility after loading has
      been detected at the time of this writing, 8 months after the procedure's
      completion, and the esthetic result is considered satisfactory by the patient and
      practitioners.

PMID- 15500060
TI  - Bond strengths of current adhesive systems on intact and ground enamel.
AB  - PURPOSE: The goal of this study was to compare the microshear bond strengths of
      current adhesive systems to intact and ground enamel surfaces. MATERIALS AND
      METHODS: Three commercially adhesive materials were examined: a two-step total
      etching self-priming system (Single Bond, 3M ESPE, St. Paul, MN, USA), a two-step
      self-etching system (Clearfil SE Bond, Kuraray Co. Ltd., Osaka, Japan), and an
      all-in-one system (One-Up Bond F, Tokuyama Dental, Tokyo, Japan). The labial
      surfaces of extracted human incisors were used. For intact enamel surfaces, the
      teeth were polished with pumice. However, for the ground enamel, 0.5 mm deep,
      flat enamel surfaces at the midlabial aspect were ground with a no. 600 grit
      silicon carbide paper. Ground and intact enamel surfaces were bonded with one of
      three bonding systems and a resin composite and were subjected to a microshear
      bond test. RESULTS: The two self-etching systems demonstrated lower bond
      strengths than did the total-etching system on intact enamel (One-Up Bond F,
      18.59 MPa; Clearfil SE Bond, 35.71 MPa; Single Bond, 47.20 MPa). No significant
      difference was found between the total-etching system and the two-step self
      etching system on ground enamel (One-Up Bond F, 28.96 MPa; Clearfil SE Bond,
      48.51 MPa; Single Bond, 51.07 MPa). Shear bond strengths on ground enamel were
      significantly higher than those on intact enamel except for the group that was
      bonded with the total-etching system. CONCLUSIONS: The two-step adhesives showed
      significantly higher bond strengths than did the one-step adhesive. When applying
      the total-etching system, no significant differences in bond strength were
      demonstrated between bonding to intact and to ground enamel.

PMID- 15500061
TI  - Accelerated aging effects on color and translucency of bleaching-shade
      composites.
AB  - PURPOSE: This study was performed to evaluate the influence of accelerated aging
      on the color and translucency parameter (TP) of bleaching-shade resin composites.
      MATERIALS AND METHODS: Thirty-three bleaching shades and two control conventional
      shades of microhybrid (MH) and microfill (MF) resin composite specimens (n = 5)
      were aged in an accelerated aging chamber set to standard CAM 180 cycles. One
      side of each specimen was evaluated for surface color and TP changes compared
      with baseline in increments of 150 kJ/m2 for intervals up to 450 kJ/m2 using a
      spectrophotometer. A deltaE* > or = 3.7 was considered to be a poor match, and
      the total TP range was divided into three equal parts representing low, medium,
      and high translucency. Data were analyzed with analysis of variance. RESULTS:
      Compared to the baseline, deltaL*, deltaa*, deltab*, and deltaE* ranges at 450
      kJ/m2 were -0.8 to 5.0, -0.6 to 1.2, -8.3 to 0.0, and 0.7 to 8.6 for MH and 0.2
      to 1.3, 0.1 to 1.3, -2.5 to 1.1, and 1.7 to 2.7 for MF composites. Scheffe's S
      intervals (p = .05) for comparisons of deltaL*, deltaa*, deltab*, and deltaE*
      values of MH composites between baseline and 450 kJ/m2 were 1.6, 0.6, 1.7, and
      1.5, respectively. Corresponding Tukey-Kramer intervals for MF composites were
      0.7, 0.3, 0.6, and 0.6, respectively. TP values at baseline ranged from 0.9 to
      4.3 for MH and from 1.4 to 2.2 for MF composites, whereas deltaTP for baseline
      minus 450 kJ/m2 ranged from -1.1 to 1.7 for MH and from -0.1 to 0.3 for MF
      composites. Scheffe's S interval (p = .05) for comparisons of deltaTP values of
      MH composites for baseline minus 450 kJ/m2 was 1.0. Corresponding Tukey-Kramer
      interval for MF composites was 0.4. CONCLUSIONS: Aging-dependent color changes at
      450 kJ/m2 were above the limit that indicated a poor match for 18/26 MH, while
      corresponding values for microfills were within acceptable range. Accelerated
      aging generally caused decreases in L* (specimens became darker) and a* values
      (specimens became redder), while b* values increased (specimens became more
      chromatic) for both MH and MF composites. TP was relatively stable during aging
      for both MH and MF composites.

PMID- 15500063
TI  - All-ceramic crown.

PMID- 15500062
TI  - Influence of cavity configuration on microleakage around Class V restorations
      bonded with seven self-etching adhesives.
AB  - PURPOSE: The purpose of this study was to evaluate microleakage around Class V
      resin composite restorations with different cavity configurations, bonded with
      one of seven self-etching materials or with an adhesive using the total-etch
      technique. MATERIALS AND METHODS: Ninety-six human molars and premolars were
      randomly assigned to eight groups and bonded with one of seven self-etching
      adhesives--Prompt-L-Pop (3M ESPE, St. Paul, MN, USA), Adper Prompt-L-Pop (3M
      ESPE), Clearfil SE Bond (Kuraray Medical, Okayama, Japan), Prime & Bond NT/NRC
      (Dentsply DeTrey, Konstanz, Germany), Xeno III (Dentsply DeTrey), One-Up Bond
      (Tokuyama Dental, Tokuyama, Japan), AdheSE (Ivoclar Vivadent, Schaan,
      Liechtenstein)-or with Prime & Bond NT (Dentsply DeTrey) using a separate total
      etch technique. Cavities were cut in both the lingual and buccal surfaces and
      were approximately 3 mm mesiodistally, 1.5 mm deep, and 2.0 mm occlusogingivally.
      Selected at random, box-shaped cavities were cut on one side and V-shaped
      cavities were cut on the contralateral side. After bonding, the cavities were
      incrementally filled with a microhybrid composite (Tetric Ceram, Ivoclar
      Vivadent), cured, and immediately polished with Sof-Lex (3M ESPE) disks. The
      teeth were thermocycled, and the specimens were examined for microleakage using
      Procion Brilliant Red (ICI, Slough, UK) as a marker. RESULTS: Comparisons of both
      gingival and enamel margins within each of the groups showed no significant
      difference owing to configuration factor (C-factor; p > .5 in all cases,
      calculated with Kruskal-Wallis nonparametric analysis of variance [ANOVA]) and
      Dunn's multiple comparison test). All groups showed microleakage at the gingival
      margins irrespective of C-factor or bonding agent (box-shaped cavities, p =
      .8862; V-shaped cavities, p = .9623; using the ANOVA). Microleakage was not
      observed at all enamel margins regardless of C-factor or bonding agent, and there
      were no significant differences between the groups (box-shaped cavities, p =
      .9869; V-shaped cavities, p = .9550; using the Kruskal-Wallis nonparametric
      ANOVA).

PMID- 15500064
TI  - Flavonoids and resveratrol as regulators of Ah-receptor activity: protection from
      dioxin toxicity.
AB  - In 2002 FAO and WHO published a joint appeal to state and public organizations
      and scientific community to take every effort to control the contents of dioxin
      and related biphenyls in the environment and food products. The toxic effects of
      dioxin are realized via its interaction with the Ah-receptor. Here we reviewed
      modern notions about the structure and functions of Ah-receptor. Particular
      attention was given to antagonists and agonists of the Ah-receptor, including
      various flavonoids and resveratrol.

PMID- 15500065
TI  - Influence of changes in intrathoracic and central venous pressure on cardiac
      filling dynamics.
AB  - Changes in the ratio between intrathoracic and central venous pressure were
      studied in narcotized cats under conditions of constant positive or negative
      pressure ventilation. Transformation of elastic characteristics in the
      respiratory system caused by changes in intrathoracic pressure led to inversion
      of the ratio between transpulmonary intrathoracic and central venous pressure
      determining right atrial filling pressure.

PMID- 15500066
TI  - S100B protein in pro- and antiapoptotic doses produces different effects on
      defensive behavior in adult rats.
AB  - We studied the effects of S100b protein in doses stimulating (500 and 50 ng) or
      inhibiting (5 ng) apoptosis in nerve cells on acquisition, retention, and
      retrieval of extinction of the acoustic startle response and conditioned fear in
      adult rats. After application to the vermis of the cerebellum S100b protein in
      doses of 500 and 50 ng impaired, while in a dose of 5 ng facilitated acquisition
      of both forms of defensive behavior. Different behavioral effects of S100b
      protein are probably related to its pro- and antiapoptotic effects on cerebellar
      cells relevant to the studied forms of behavior. Our results suggest that
      regulators of apoptosis are involved in the mechanisms of learning and memory.

PMID- 15500067
TI  - Dependence of the nonspecific resistance in cows from their physiological and
      clinical state.
AB  - In cows phagocytic, bactericidal, and lysozyme activity increased with increasing
      pregnancy term, decreased by the 2nd day after labor, and increased in the follow
      up period. The nonspecific resistance decreased most significantly in the winter
      spring period.

PMID- 15500068
TI  - Expression of vascular endothelial growth factor during neoangiogenesis
      stimulated by exposure to high-intensity laser radiation.
AB  - Expression of vascular endothelial growth factor was studied during
      neoangiogenesis stimulated by exposure of ischemic tissues in the limb muscles,
      liver, and myocardium and normal myocardial tissue to high-intensity laser
      radiation. Changes in expression were related to cell reactions during the
      inflammatory and reparative process and did not differ in the studied tissues.

PMID- 15500069
TI  - Megakaryocytopoiesis under hypoxic conditions.
AB  - Acute and chronic hypoxia led to acceleration of proliferation and
      differentiation of bone marrow megakaryocytes and increase in their functional
      activity. The count of young cells in the peripheral blood increased during acute
      hypoxia. Chronic hypoxia led to increase in the number of old platelets with
      lower functional activity, which was accompanied by thrombocytosis.

PMID- 15500070
TI  - Influence of estrogen cytostatics on activity of plasma membrane enzymes 5'
      nucleotidase and N+-K+-ATPase.
AB  - We studied the effect of four conjugated synthetic derivatives of estrone and
      ethynylestradiol and bis-beta-chloroethylamine-containing substance on activity
      of plasma membrane enzymes 5'-nucleotidase and N+-K+-ATPase. As differentiated
      from precursors, estrogen cytostatics decreased activity of plasma membrane
      enzymes. Reference preparations chlorophenacyl and estradiol had little effect on
      activity of 5'-nucleotidase and N+-K+-ATPase. These data suggest that damage to
      plasma membrane enzymes is related to the effect of estrogen cytostatic
      molecules. Test compounds produced an antiproliferative effect on estrogen
      independent tumor cells, which strongly correlated with a decrease in activity of
      plasma membrane enzymes 5'-nucleotidase and N+-K+-ATPase. The derivative of
      ethynylestradiol with the cytostatic residue in the 3-position of the steroid
      nucleus (Po-714-11alpha) most significantly modulated enzyme activity.

PMID- 15500071
TI  - Protective effect of phenyl-t-butylnitrone in rats with focal cerebral ischemia.
AB  - Phenyl-t-butylnitrone produces a potent neuroprotective effect in rats with focal
      cerebral ischemia modeled by distal occlusion of the middle cerebral artery. The
      infarction area markedly decreased after treatment with phenyl-t-butylnitrone.
      The content of phenyl-t-butylnitrone in the brain, liver, and kidneys was
      measured by the method of electron paramagnetic resonance.

PMID- 15500072
TI  - Effect of chronic caffeine consumption on changes in locomotor activity of WAG/G
      and Fischer-344 rats induced by nicotine, ethanol, and morphine.
AB  - We studied the effect of single treatment with nicotine, ethanol, and morphine on
      locomotor activity of WAG/G and Fischer-344 rats chronically drinking caffeine
      solution. In Fischer-344 rats receiving caffeine locomotor activity in the open
      field test was much lower than in animals drinking water, while in WAG/G rats no
      differences in locomotor activity were found. Chronic caffeine intake increased
      rat sensitivity to the stimulating effect of nicotine and ethanol, but decreased
      their sensitivity to the depressant effect of morphine. Chronic caffeine
      treatment most significantly modulated the effects of nicotine, ethanol, and
      morphine in Fischer-344 rats.

PMID- 15500073
TI  - Comparative efficiency of low-esterified pectin and antistrumin during
      experimental hypofunction of the thyroid gland.
AB  - We studied the effects of low-esterified pectin and antistrumin in rats with
      hypofunction of the thyroid gland modeled by enteral administration of lead
      acetate. Pectin more rapidly recovered thyroid function than iodine.

PMID- 15500074
TI  - Effect of ivermectin on function of liver macrophages.
AB  - Ivermectin had no effect on phagocytic function of liver macrophages, but blocked
      LPS-induced secretion of tumor necrosis factor, NO, prostaglandin E2, and
      increase of intracellular concentration of Ca2+. These inhibitory effects were
      observed only in the presence of chlorine ions in the extracellular medium, which
      attested to involvement of glycine-dependent chlorine channels.

PMID- 15500075
TI  - Effects of flavonoids on the resistance of microsomes to lipid peroxidation in
      vitro and ex vivo.
AB  - Incubation of rat liver microsomes with preparations of grape flavonoids,
      dihydroquercetin, and silibinin increased their resistance to lipid peroxidation
      induced by NADPH-Fe2+. This was manifested in less pronounced accumulation of
      lipid peroxidation products and changes in activity of microsomal enzymes induced
      by lipid peroxidation. In vitro antioxidant activity of grape flavonoids markedly
      surpassed that of dihydroquercetin and silibinin. Addition of flavonoids into
      fodder led to moderate, statistically significant, and similar increase in the
      resistance of rat liver microsomes to ex vivo induced lipid peroxidation.

PMID- 15500076
TI  - Changes in the steady-state potential in rats with focal cerebral ischemia
      receiving cyclopentyladenosine.
AB  - Brain function and neuroprotective activity of cyclopentyladenosine in rats with
      focal cerebral ischemia were evaluated by recording the steady-state potential.
      Cerebral ischemia was modeled by intravasal occlusion of the left internal
      carotid and middle cerebral arteries and bilateral occlusion of the common
      carotid arteries. Recording of the steady-state brain potential during
      experimental ischemia allowed identifying the development of ischemic
      depolarization by a negative potential shift. Changes in the steady-state
      potential after cyclopentyladenosine administration reflected delayed development
      of ischemic depolarization in the nervous tissue. Cyclopentyladenosine holds much
      promise for the protection of nerve cells from ischemic injury.

PMID- 15500077
TI  - Effect of lauric acid on transdermal penetration of phenazepam in vivo.
AB  - We studied the effect of lauric acid on transdermal penetration of phenazepam in
      vivo. It was found that treatment with lauric acid 3-fold increased the maximum
      anticonvulsive effect of phenazepam applied in a transdermal therapeutic system
      in comparison with the control. Study of the pharmacokinetics of phenazepam
      transdermal therapeutic system showed its higher bioavailability in the presence
      of lauric acid (f=0.9).

PMID- 15500078
TI  - Experimental study of the use of Perftoran for preventing the formation of
      postoperative adhesions in peritonitis.
AB  - The effect of Perftoran (perfluorocarbon compound) on cells of the peritoneal
      exudate and small intestinal serosa was studied in Wistar rats with experimental
      peritonitis and mechanical injury. The peritoneal cavity was treated with
      Perftoran for preventing postoperative adhesions and the mechanisms of reparative
      regeneration of the mesothelium after this treatment were studied by
      immunohistochemical methods and scanning electron microscopy. The increase in
      macrophage population during the early postoperative period and its decrease at
      later terms prevented fibroblast activation and promoted epithelialization as
      early as by day 5.

PMID- 15500079
TI  - Effect of extracts from Rhodiola rosea and Rhodiola crenulata (Crassulaceae)
      roots on ATP content in mitochondria of skeletal muscles.
AB  - We studied the effects of oral treatment with extracts from Rhodiola rosea (50
      mg/kg) and Rhodiola crenulata (50 mg/kg) roots on the duration of exhaustive
      swimming and ATP content in mitochondria of skeletal muscles in rats. Treatment
      with R. rosea extract significantly (by 24.6%) prolonged the duration of
      exhaustive swimming in comparison with control rats and rats treated with R.
      crenullata. R. rosea extract activated the synthesis or resynthesis of ATP in
      mitochondria and stimulated reparative energy processes after intense exercise.
      Experiments proved different pharmacological characteristics of R. rosea and R.
      crenulata: R. rosea is most effective for improving physical working capacity.

PMID- 15500080
TI  - Parameters of cell immune response in Wistar and OXYS rats and their behavior in
      the open field test.
AB  - Comparative analysis of the state of the thymus, activity of cell component of
      the immune system, and open field behavior of Wistar and OXYS rats showed early
      involution of the thymus in OXYS rats. By morphological picture this involution
      corresponded to accidental involution and was paralleled by low level of delayed
      hypersensitivity reaction and by inhibition of motor and exploratory behavior.

PMID- 15500081
TI  - Phytoadaptogen for preventive oncology: immunobiological criteria of composition.
AB  - A system of in vitro immunobiological tests is developed for screening of
      phytopreparations intended for the use as immunomodulators in oncology.
      Proliferative activity of human tumor cells decreased after treatment with
      complex phytoadaptogen. The immunomodulatory effect of this phytoadaptogen on
      immunocompetent cells of cancer patients and its nonspecific interferonogenic
      effect were detected. The composition of adaptogenic complex for preventive
      oncology is determined.

PMID- 15500082
TI  - Effect of neuronol on lifespan and development of spontaneous tumors in SAMP-1
      mice with genetically accelerated aging.
AB  - Treatment of female SAMP-1 mice with Neuronol (drug containing succinic acid)
      given with drinking water starting from the age of 2 months during the whole life
      prolonged the lifespan and markedly reduced mortality of animals aged 1.5-2
      years. Neuronol inhibited the development of spontaneous tumors, primarily
      lymphomas, and significantly prolonged lifespan in mice with tumors. Long-term
      treatment with Neuronol had no pathological side effects. Our experiments
      demonstrated geroprotective and anticarcinogenic activity of Neuronol and safety
      of its long-term use.

PMID- 15500084
TI  - Effect of pinealectomy on circadian rhythm of spermatogenesis.
AB  - The mitotic index of spermatogonia and 24-h dynamics of stages IV, VI, and XIV of
      spermatogenic cycle are characterized by circadian rhythm. No circadian rhythm
      was detected for 11 of 14 stages. Pinealectomy led to an increase of the mitotic
      index of spermatogonia but did not modulate the incidence of spermatogenic cycle
      stages, and led to disappearance of the circadian rhythm of both the mitotic
      index and spermatogenic cycle stages.

PMID- 15500083
TI  - Spatiotemporal organization of the proliferative system in small intestinal crypt
      epithelium of intact mice.
AB  - We studied spatiotemporal organization of the proliferative system in small
      intestinal crypt epithelium of normal mice. Close relationships were found
      between circadian rhythms of cell proliferation and their position in the crypt.
      These peculiarities reflected spatiotemporal organization of the crypt
      epithelium. The hierarchic structure of spatiotemporal organization suggests the
      existence of several interrelated levels (individual cells, cell subpopulations,
      and cells with basal and maximum levels of proliferation within subpopulation).
      Each level has its proper temporal and spatial characteristics. Their interaction
      determines spatiotemporal organization of the proliferative system in the small
      intestinal crypt epithelium.

PMID- 15500085
TI  - Effects of alternative social experience on the sexual function of male mice.
AB  - The relevance of the social contact test "Wall" for evaluation of sexual
      motivation of male mice was tested and confirmed. Motivation of C57BL/6J male
      mice with alternative social experience (winners and victims in 10 and 20 daily
      male-male confrontations) was evaluated. Elevated primary sexual interest was
      detected in aggressive animals after 10 confrontations, while in submissive
      animals this interest was decreased; however after 20 confrontations sexual
      motivation in both groups was characterized by rapid exhaustion and low basal
      level of testosterone. Hence, the sexual function of male mice is inhibited under
      conditions of long social conflicts irrespective of previous experience of
      victories or defeats in male-male confrontations.

PMID- 15500086
TI  - Benzo[alpyrene induction of cytochrome P450 1A1/1A2 in the lymph nodes of rats.
AB  - Studies of mesenteric lymph nodes of rats by indirect immunoperoxidase method
      using monoclonal antibodies to cytochrome P450 1A/1A2 after oral dose of
      benzo[a]pyrene showed the presence of these cytochrome forms in monocytes,
      macrophages, reticular and litoral cells, cell detritus, and liquid contents of
      the paracortical zone and medullary substance sinuses. Oxidation of various exo-
      and endogenous toxins in the lymph nodes was revealed.

PMID- 15500087
TI  - A method for biological control of a complex phytoadaptogen.
AB  - We propose a method for standardization of complex adaptogen-containing
      preparations. The method is based on acceleration of baking yeast strain growth
      on energy-depleted medium in the presence of the test agent. This method allows
      simple quantitative biological control of phytoadaptogens and comparison of
      adaptogenic activity of mono- and complex preparations.

PMID- 15500088
TI  - [Pre- and postoperative chemotherapy for lung carcinoma].
AB  - The role of pre- and postoperative chemotherapy has been evaluated in non-small
      cell lung carcinoma, in particular locally advanced carcinomas. It has been
      stated in numerous reports that in stage IIIA, so-called N2 lung carcinoma,
      patients who receive induction chemotherapy have better survival rates compared
      with those who do not. In the expectation that postoperative survival could be
      prolonged in patients with stage IB and II lung cancer, various controlled trials
      have been performed in many countries, including Japan. Currently, induction
      chemoradiotherapy for stage III disease is being evaluated worldwide.

PMID- 15500089
TI  - [Current status of sentinel node adenectomy and future perspectives].
AB  - Sentinel node adenectomy has rapidly been accepted in recent years. A survey
      performed under the auspices of the Japanese Breast Cancer Society revealed that
      about 40% of institutions in Japan have already introduced sentinel lymph
      adenectomy. Analysis of questionnaire responses from 40 institutions in Japan
      revealed an identification rate using the dye method alone of 87% compared with
      96% using the combined method. The identification rate and the false-negative
      rate are about the same among various methods used such as colloidal
      radiotracers, injection site, use of lymphoscintigraphy, etc., provided that the
      surgeon has adequate experience. It is recommended that the surgeon should start
      to perform sentinel node adenectomy after experiencing more than 60 cases,
      because there is a learning curve. Some investigators are devising other methods
      to replace the RI method, for example, using magnetic particles instead of RI
      colloid and detecting them using magnetic probes. and a trial to detect lymphatic
      flow with CT after local injection of contrast medium is also being conducted.
      Sentinel node adenectomy may become a standard technique for early breast cancer
      patients in the near future.

PMID- 15500090
TI  - [Definitive chemoradiotherapy and salvage esophagectomy for squamous cell
      carcinoma of the esophagus].
AB  - Surgical resection has widely accepted as the first-choice treatment for
      esophageal carcinoma in Japan, and it has improved the survival of patients with
      esophageal carcinoma during the past decades. However, the survival rate remains
      relatively poor compared with that of other gastrointestinal carcinomas. Physical
      handicaps after esophagectomy also cannot be ignored. Definitive chemoradiation
      has become an accepted treatment for esophageal carcinoma. Persistent or
      recurrent local disease is often the problem to be solved. In this case, selected
      patients with local failures can be salvaged by esophagectomy. In this paper we
      discuss recent improvements in definitive chemoradiotherapy and the definition of
      salvage esophagectomy. We also present our short-term results of a prospective
      phase II study of definitive chemoradiotherapy and salvage esophagectomy in
      patients with resectable squamous cell carcinoma of the esophagus.

PMID- 15500091
TI  - [Gastric cancer: laparoscopic surgery and adjuvant chemotherapy].
AB  - Demands for minimally invasive treatments for early gastric cancer and improved
      efficacy of recent chemotherapy regimens for advanced gastric cancer have led to
      considerable changes in the modality of treatment Laparoscopic gastrectomy (LG)
      with lymph node dissection is widely performed as minimally invasive surgery. The
      number of LGs is increasing each year. However, the results of a nationwide
      questionnaire survey performed by the Japanese Society for Endoscopic Surgery
      indicated that there are some postoperative complications associated with
      gastrointestinal anastomosis. In this paper, we describe our experiences with a
      unique intracorporeal surgical technique to prevent such complications. Although
      adjuvant chemotherapy is frequently administered to patients with advanced
      gastric cancer, no randomized controlled trial (RCT) has confirmed the prognostic
      significance of adjuvant chemotherapy, although some meta-analyses have. Since a
      number of published reports demonstrated the survival benefit of chemosensitivity
      test-guided chemotherapy after surgery for gastric cancer, we propose a protocol
      to perform a RCT to clarify whether chemosensitivity tests in adjuvant
      chemotherapy for gastric cancer have a significant impact.

PMID- 15500092
TI  - [Laparoscopic surgery for advanced colorectal cancer].
AB  - Laparoscopic colectomy for benign diseases and early cancers has been widely
      accepted since the first report on it was published in 1991. The indications for
      laparoscopic colectomy have been expanded with advances in the operative
      technique and instrumentation. Although laparoscopic surgery for advanced
      colorectal cancer is technically feasible, the long-term outcome should be
      confirmed in prospective, randomized, controlled trials of laparoscopic surgery
      in the treatment of advanced colorectal cancer.

PMID- 15500093
TI  - [Treatment of hepatocellular carcinoma: with special emphasis on liver
      transplantation].
AB  - A variety of therapeutic options have been developed over the past 25 years for
      the treatment of hepatocellular carcinoma. With advances in antiviral treatment
      for hepatitis viruses and improvements in surgical techniques, adult-to-adult
      living-donor liver transplantation has been increasingly carried out in Japan
      over the past 6 years. The Japanese national health insurance system began to
      cover adult-to-adult living-donor transplantation from January 2004, which is
      expected to increase the number of such surgeries. In this review, various
      therapeutic modalities for the treatment of hepatocellular carcinoma are
      discussed, with special emphasis on hepatic resection and liver transplantation.

PMID- 15500094
TI  - [Palliation of psychiatric complications in patients with cancer].

PMID- 15500095
TI  - [A physician in charge].

PMID- 15500096
TI  - [The effects of Na+ -H+ exchange inhibitor, KB-R9032, administered at the time of
      reperfusion in perfused rat heart].
AB  - BACKGROUND: We have reported that pretreatment with KB-R9032, a newly developed
      Na+ -H+ exchange inhibitor is protective against reperfusion-induced ventricular
      arrhythmia in the isolated perfused rat heart. This study was conducted to
      elucidate whether the drug is equally effective when it is given at the time of
      reperfusion. METHODS: Male Wistar rat hearts (n=32, 16 for each group) were
      perfused by means of Langendorff technique. Each heart was subjected to regional
      ischemia (occlusion of the left anterior descending coronary artery for 11
      minutes) and to three minutes of reperfusion (release of the occlusion). KB-R9032
      4 mg (one shot group) or a vehicle without drug (control) were given 30 seconds
      before the reperfusion to 30 seconds after the reperfusion. RESULTS: In the
      control group reperfusion-induced ventricular fibrillation (VF) occurred in 91.7%
      and the duration was 165 +/- 14.4 seconds, but, in one shot group, the incidence
      of VF decreased to 6.3% and the duration of VF was reduced to 0.4 +/- 0.4
      seconds, respectively (P<0.05 vs control group). CONCLUSIONS: It has been shown
      in this study that the Na+/H+ exchange inhibitor KB-R9032 given at the time of
      reperfusion suppresses reperfusion arrhythmias in the ischemia-reperfusion model
      of isolated rat heart.

PMID- 15500097
TI  - [Effects of surface anesthesia of the pharyngeal mucous membrane on negative
      pressure airway reflex].
AB  - BACKGROUND: Upper airway reflexes include a reflex protecting the airway as well
      as another one dilating the airway. The latter reflex, the pharyngeal dilator
      reflex to negative airway pressure (NPAR), plays an important role in maintaining
      airway patency, although the peripheral receptors involved in NPAR have not been
      specified. METHODS: The effects of surface anesthesia of the pharyngeal mucous
      membrane on NPAR were evaluated by observing activity of the musculus
      genioglossus (GG) in rabbits. Following anesthesia with thiopental, two incisions
      were made on the trachea of each rabbit. Through these incisions, a tube
      connected to the anesthetic circuit was inserted into the lung and another tube
      connected to an aspirator into the pharynx. Effects of negative pressure on the
      myelogram of the GG were recorded with and without surface anesthesia with 1%
      lidocaine. RESULTS: Electric discharge from the GG was increased in the sessions
      with exposure to negative pressure without surface anesthesia, but was
      significantly decreased in those with surface anesthesia. CONCLUSIONS: These
      findings suggest that the peripheral receptors of NPAR are located in the
      pharyngeal mucous membrane.

PMID- 15500099
TI  - [In vitro evaluation of lubrication properties of a suction catheter].
AB  - BACKGROUND: Lubrication is an important factor for passage of a suction catheter
      through a tracheal tube. This study was carried out to evaluate the effects of
      lubricants on resistance against removal of a suction catheter from a tracheal
      tube in an experimental setting. METHODS: A tracheal tube (I.D. of 7.5mm) was
      inserted into a mannequin, and the resistance against removal of a suction
      catheter from the tube was measured. RESULTS: Lubrication was improved by using a
      lubricant (lidocaine jelly or KY jelly), but there was no difference between the
      effects of the two lubricants. The use of water as lubricant markedly decreased
      lubrication. Differences in lubrication depending on the type of tracheal tube
      used, probably due to differences in coating, were also found. CONCLUSIONS: The
      use of water as a lubricant is not recommended for tracheal suction.

PMID- 15500098
TI  - [Glucose attenuating local anesthetic-induced hemolysis].
AB  - BACKGROUND: The effect of glucose on local anesthetic-induced neural damage has
      not been fully studied. We examined the effect of glucose on hemolysis induced by
      local anesthetics. METHODS: The mean EC50 values (the local anesthetic level that
      causes destruction of half of the red blood cells in vitro) of lidocaine HCl,
      tetracaine HCl and dibucaine HCl were determined with 0% and 7.5% glucose
      contained in Krebs solution at pH 6.4. RESULTS: The mean EC50 values of lidocaine
      HCl, tetracaine HCl, and dibucaine HCl in 0%-glucose Krebs solution were 6.51%,
      0.45%, 0.17%, respectively, which increased significantly to 7.05%, 0.64% and
      0.23%, in 7.5% glucose Krebs solution at pH 6.4. CONCLUSIONS: Glucose may have a
      protective role in local anesthetic-induced neural damage.

PMID- 15500100
TI  - [Preoperative evaluation, anesthetic management and postoperative complications
      of athetotic type cerebral palsy patients undergoing laminoplasty].
AB  - BACKGROUND: The patients with athetotic type cerebral palsy need to have their
      necks fixed for preventing worsening of their symptoms during surgery. Cervical
      fixation with a halo vest leads to difficult tracheal intubation and possibility
      of aspiration. Therefore careful perioperative management is necessary,
      especially for respiratory complications. However, since it is difficult on the
      patients with cerebral palsy to perform spirogram correctly, their preoperative
      respiratory functions are hard to be evaluated. METHODS: We evaluated the
      relationships between preoperative condition and postoperative complications in
      50 athetotic type cerebral palsy patients who had undergone laminoplasty. In
      addition, we also compared them with non-cerebral palsy patients for laminoplasty
      without a halo vest. RESULTS: The patients with cerebral palsy showed lower
      preoperative ADL score, severer symptoms of myelopathy, and decreased %VC in
      spirogram. We found all of these were related to prolonged postoperative recovery
      of ADL and longer hospitalization. Two patients with cerebral palsy suffered from
      aspiration pneumonia after operation, whereas any non-cerebral palsy patients had
      no remarkable complications. CONCLUSIONS: Careful perioperative management is
      necessary for cerebral palsy patients undergoing laminoplasty, especially for
      prevention of aspiration pneumonia.

PMID- 15500101
TI  - [Postoperative course after first-stage palliation of hypoplastic left heart
      syndrome with right ventricle-to-pulmonary artery shunt; compared with classic
      Norwood procedure].
AB  - BACKGROUND: A recent modification of the Norwood procedure involves the use of a
      right ventricle-to-pulmonary artery (RV-PA) shunt to provide pulmonary blood flow
      for patients with hypoplastic left heart syndrome (HLHS). We investigated the
      hemodynamics after first-stage palliation of HLHS with RV-PA shunt compared with
      classic Norwood procedure with subclavian-to-pulmonary artery (BT) shunt.
      METHODS: The postoperative course of 12 infants who had undergone first-stage
      palliation for HLHS using BT shunt (group BT: n=6) and RV-PA shunt (group RV-PA:
      n=6) were retrospectively reviewed and we obtained the following data: blood
      pressure, heart rate, inotropic support, atrial pressure, lactate, base excess,
      PaO2, FIO2. RESULTS: The RV-PA shunt using a non-valved conduit provided higher
      diastolic blood pressure than the BT shunt, but no significant difference in
      heart rate, systemic blood pressure, inotropic support and atrial pressure was
      observed between the two groups. Although the infants in the group RV-PA required
      significantly more myocardial ischemic time for operative procedure than those in
      the group BT, the serum lactate level in the group RV-PA was significantly lower
      than those in the group BT. CONCLUSIONS: These results show that the RV-PA shunt
      provides a stable systemic circulation and abundant tissue oxygen supply.
      Excellent hemodynamics provided by RV-PA shunt is beneficial for infants
      undergoing stage I palliation for HLHS.

PMID- 15500102
TI  - [Spinal anesthesia with isobaric 0.5% bupivacaine for lower limb surgery: effects
      of different volumes].
AB  - BACKGROUND: The effects of different volumes (2.4, 2.6, 2.8 and 3.0 ml) of
      isobaric 0.5% bupivacaine used for spinal anesthesia were compared in 206
      patients scheduled for lower limb surgery. METHODS: The spinal anesthesia was
      performed with the patients in the lateral position and the isobaric 0.5%
      bupivacaine was injected intrathecally at the L3-4 interspace. RESULTS: The time
      to maximum cephalad spread of anesthesia (loss of cold sensation) varied between
      25 and 40 min. A significant difference was found in cephalad spread between 2.4
      ml group and 3.0 ml group (T11 vs T7), and between 2.6 ml group and 3.0 ml group
      (T11 vs T7). Severe hypotension did not occur during the study. CONCLUSIONS:
      Spinal anesthesia with 2.8 ml of isobaric 0.5% bupivacaine proved satisfactory
      for lower limb surgery.

PMID- 15500103
TI  - [Comparison of the effects of colloid and crystalloid solution for volume
      preloading on maternal hemodynamics and neonatal outcome in spinal anesthesia for
      cesarean section].
AB  - BACKGROUND: The role of crystalloid or colloid preloading to prevent hypotension
      associated with spinal anesthesia in parturients during cesarean section has
      recently been questioned. The aim of the current study was to investigate the
      effects of volume preload with either crystalloid or colloid, or with no preload
      on changes of maternal hemodynamics and neonatal outcomes. METHODS: After written
      informed consent had been obtained from each patient, thirty-two healthy
      parturients undergoing cesarean section were randomized to receive either
      acetated Ringer's solution (1,000 ml, n=8, AR group), 6% hydroxyethylstarch
      (1,000 ml, n=9, HES group), or no preload (n=10) before spinal anesthesia. In
      addition, emergency cases (n=5) such as prolonged labor without any maternal
      complication were also included for analysis. The incidence of hypotension,
      systolic blood pressure <80% of baseline or <100 mmHg, and the amount of
      ephedrine used to treat hypotension were compared. Neonatal outcome was also
      assessed measuring pH and lactate concentration in umbilical arterial blood
      samples. Apgar score was also measured at 1 and 5 min after delivery. RESULTS:
      There was no difference in demographic characteristics among the four groups.
      Minimal systolic arterial pressure (SAP) after spinal anesthesia did not differ
      among AR, HES, and no preload groups. However, a significant decline in SAP was
      observed in emergency group (82.2 +/- 14.3 mmHg, P<0.05). Although there was no
      difference in umbilical arterial blood pH, lactate concentration was
      significantly higher in emergency group (3.7 +/- 1.0 mmol x l(-1), P<0.01) than
      those of other groups. Apgar score at 1 min after delivery was significantly
      lower in emergency group. CONCLUSION: In healthy patients with full-term
      pregnancy, volume preloading has little effect on maternal hemodynamics and
      neonatal outcomes, suggesting that stable perioperative management is possible
      with or without volume preload before spinal anesthesia. However, preloading may
      be needed for prevention of hypotension in emergency cases.

PMID- 15500104
TI  - [Management of sevoflurane anesthesia for a patient with multiple drug
      allergies].
AB  - There have been several reports on anesthesia for a patient with a history of
      multiple drug allergies. We present here anesthesia for a 33-year-old woman with
      histories of multiple drug allergies. She was scheduled to undergo total
      abdominal hysterectomy. We could not perform preoperative screening of the drugs
      using a dermal test because of a high risk of anaphylactic shock. Anesthesia was
      induced and maintained with sevoflurane and nitric oxide. The operation was
      finished without complications and her postoperative course was uneventful. It is
      important preoperatively to obtain histories of allergies adequately for
      recognition of allergens.

PMID- 15500105
TI  - [Anesthetic management of a patient with acute idiopathic pandysautonomia].
AB  - Acute idiopathic pandysautonomia (AIPD) is a very rare disease with acute onset
      of impairment in the peripheral sympathetic and parasympathetic nerves. We report
      the anesthetic management of a patient with AIPD undergoing bladder lithotomy and
      scrotum abscess drainage. A 64-year-old man had a severe orthostatic hypotension,
      and was extremely sensitive to intravenous norepinephrine because of denervation
      hypersensitivity. Before the surgery, the patient was sufficiently hydrated. We
      planned to administer a vasopressor (phenylephrine) and a vasodilator
      (nicardipine) at 1/10 of usual doses. After placement of a radial artery
      catheter, combined epidural and spinal anesthesia was performed with the patient
      in a right lateral position. Blood pressure decreased slightly after placing him
      in a supine position. However, no medication was needed, and the patient showed
      no perioperative complications.

PMID- 15500106
TI  - [Case of radial nerve injury induced by withdrawing a catheter from the cephalic
      vein].
AB  - There are many reports of neuropathic pain describing nerve injuries sustained by
      sticking or penetrating nerves by metal needles on venipuncture. However, there
      was no previous report of neuropathic pain caused by withdrawing a catheter from
      the vein as in this case. Neuropathic pain in this case was quickly cured by
      intravenous ketamine hydrochloride and stellate ganglion block. The neuropathic
      pain occurred when a medical student withdrew a catheter from the cephalic vein
      during clinical training. Clinical training of medical students is very important
      for medical education, but we must also recognize that this training involves
      many risks not only for patients but also for the students.

PMID- 15500107
TI  - [Case of circulatory depression in an obese patient in prone position during
      general anesthesia].
AB  - A 25-year-old man [120 kg, 180 cm (body mass index=37 kg x m(-2)] underwent
      laminectomy and discectomy under general anesthesia in the prone position. Hall
      frame was used for supporting his body. In spite of a small amount of bleeding,
      the patient showed metabolic acidosis and hypotension with limb cyanosis one hour
      after changing position. Ephedrine hydrochloride was effective for the treatment
      of his hypotension. However, limb cyanosis continued until turning him to the
      supine position. Anuria continued during prone position. We consider that Hall
      frame allows patient's abdomen to hang freely, but compresses the body more
      strongly than expected, especially with heavy patients. It is possible for
      morbidly obese patients to develop seriously inhibited circulation due to Hall
      frame. Prone position with careful selection of support system may prevent these
      complications.

PMID- 15500108
TI  - [Anesthetic management for a patient with remitting seronegative symmetrical
      synovitis with pitting edema (RS3PE) syndrome].
AB  - Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome,
      described by McCarty et al., is a form of "seronegative rheumatoid arthritis"
      characterized by an acute-onset polyarthritis with pitting edema of the dorsum of
      both hands and/or both feet. The syndrome is prevalent in elderly men, completely
      remitted with a small dose of steroid over a relatively short period, and has a
      benign clinical course. We describe a case of RS3PE syndrome in a 61-year-old man
      undergoing a lobectomy of the lung and discuss anesthetic management for the
      syndrome.

PMID- 15500109
TI  - [Sivelestat sodium hydrate was effective for ARDS in a patient suffering from
      chronic rheumatoid arthritis with acute exacerbation after failing to respond to
      high dose steroid pulse therapy].
AB  - Sivelestat sodium hydrate (ELASPOL) was effective for ARDS in a fifty-year-old
      female patient suffering from chronic rheumatoid arthritis with acute
      exacerbation, after failing to respond to high dose steroid pulse therapy. In
      ICU, the patient had bilateral lung opacities, especially of the upper lobes,
      respiratory acidosis, hypercapnea (PaCO2 89 mmHg), and poor oxygenation (P/F
      ratio 193). High dose steroid pulse therapy had been performed, but oxygenation
      was not improved, and a low level of oxygenation (P/F ratio 155) persisted.
      Sivelestat was started two days after finishing the steroid pulse therapy. The
      butterfly shadow on chest X ray and impaired oxygenation were markedly improved
      from the third day of sivelestat administration. Respiratory support was
      terminated with P/F ratio 300. Plasma concentrations of SP-A and SP-D decreased
      after sivelestat administration, but concentration of KL-6 was still elevated. In
      this case, sivelestat was effective for ARDS in the patient not responding to
      steroid pulse therapy, and clinical finding and plasma concentrations of SP-A and
      SP-D were correlated well.

PMID- 15500110
TI  - [Epidural hematoma after an epidural block in a patient with no coagulopathy].
AB  - We report a case of epidural hematoma after a single epidural block. The patient
      was a 67-year-old woman with sciatica and osteoarthritis of the spine. She had no
      coagulopathy. She underwent a single epidural block without difficulty 3 times in
      5 days. She had a lumbar MRI for an examination of the spine 4 days after the
      final epidural block. Subacute epidural hematoma of 0.8 x 1.5 x 3.0 cm was
      revealed on MRI at L 3-4. She had no new neurological symptoms. MRI 1 month later
      revealed a resolution of the hematoma. Epidural hematoma after an epidural block
      might occur in an outpatient with no bleeding tendency.

PMID- 15500111
TI  - [Acute pulmonary thromboembolism during the surgery for bilateral lower extremity
      fracture].
AB  - A 50-year-old woman underwent open reduction and internal fixation for bilateral
      lower extremity fracture under general anesthesia. During the surgery, arterial
      oxygen saturation and expired CO2 concentration dropped suddenly when the left
      limb was fixed. Immediately, we performed aspiration of the pulmonary thrombus
      and inserted a temporary infra-vena cava filter followed by heparinization. Ten
      days later, we carried out the surgery on the right limb uneventfully. The major
      cause of APTE is deep vein thrombosis (DVT), which is extremely common during
      perioperative period. Therefore, we must perform antithrombotic therapy for the
      patient at high risk for DVT.

PMID- 15500112
TI  - [Use of argatroban as a substitute for heparin in a patient with suspected HIT
      type II undergoing carotid endarterectomy].
AB  - Heparin-induced thrombocytopenia (HIT) type II is characterized by a decrease in
      platelet count and thrombosis following heparin administration. We anesthetized a
      67-year-old woman with suspected HIT type II undergoing carotid endarterectomy
      (CEA). Preoperatively, the patient had received anticoagulation therapy with
      heparin for cerebral infarction due to thrombosis and she developed
      thrombocytopenia with deterioration of cerebral infarction. Platelet level
      recovered by discontinuation of heparin and platelet infusion. During the
      surgical procedure, a substitution for heparin as an anticoagulant was necessary
      and we used argatroban, a direct thrombin inhibitor, with monitoring activated
      coagulation time (ACT). The ACT values were maintained above 200 sec during
      endoarterectomy and the operation was successfully carried out. We believe that
      argatroban is one of the choices for anticoagulants in a patient with HIT type
      II.

PMID- 15500113
TI  - [Anesthetic management for removal of a giant ovarian tumor by monitoring
      transesophageal Doppler cardiac output].
AB  - Transesophageal Doppler cardiac output was monitored in two cases for removal of
      a giant ovarian tumor. In case 1, cardiac output (CO) increased following the
      drainage of the tumor, and CO decreased following blood loss. In case 2, CO
      increased following the removal of the tumor, and remained stable because of
      small blood loss. Cardiovascular parameters changed remarkably with the drainage
      of tumors and blood loss. Therefore, noninvasive Doppler cardiac output monitor
      was useful for rapid estimation of cardiovascular changes.

PMID- 15500114
TI  - [Case of ventricular tachycardia induced by coronary spasm during surgery in
      prone position].
AB  - A 55-year-old man with hypertension was scheduled for resection of spinal tumor
      at S1 in the prone position. Anesthesia was induced with midazolam 10 mg,
      fentanyl 0.2 mg and vecuronium 10 mg, and maintained with sevoflurane 1.5-2% in
      oxygen 3 l x min(-1) and fentanyl 0.4 mg. When the interspinal ligament was
      handled, severe ST depression on the ECG was observed for 1 minute, followed by
      ventricular tachycardia (VT). Immediately, 60 mg of lidocaine was administered
      intravenously, and ventricular rhythm recovered to sinus rhythm with normal ST
      level within a few minutes, but the surgery was postponed. In the preoperative
      examinations, the patient had been evaluated as a low risk case except for a long
      history of hypertension. Coronary spasm was suspected to have induced VT, because
      it followed severe ST depression. This experience taught us that in order to
      avoid critical arrhythmia, patients under general anesthesia, especially those
      undergoing surgery in the prone position, require particular attention because of
      the difficulty in cardiac resuscitation.

PMID- 15500115
TI  - [Assessment of the quality of information on departments/divisions of
      anesthesiology available on the World Wide Web].
AB  - BACKGROUND: The quality of health information available in the World Wide Web is
      an important issue, but no review of the quality of such information has been
      performed. METHODS: We investigated the quality of information available on the
      World Wide Web regarding departments/divisions of anesthesiology in 82 specific
      functioned hospitals in Japan. RESULTS: Eighty-eight percent of the hospitals
      have their own web site for anesthesiology. Although only general clinical
      information was available on 64-71% of the web sites, detailed information on
      clinical results and members having diploma of the board was available on 11-26%
      of the sites. Regarding education, only 4% of the sites provided information on
      contents of lectures, whereas 75% of the sites have pages for medical students.
      CONCLUSIONS: Departments/divisions of anesthesiology, especially in specific
      functioned hospitals, should recognize an important role of web pages for medical
      consumers (= e-patient) and renew their web sites appropriately and opportunely.

PMID- 15500116
TI  - [Structure of the glomerular podocytes-- morphological change observed from the
      basal side].

PMID- 15500117
TI  - [History of nephrotic syndrome].
AB  - The history of nephrotic syndrome can go back to beginning of the era. In old
      Alexandria, urine was conceived to be produced in kidneys. In 1827, Bright
      classified diseases with proteinuria into three categories, and lipoid nephrosis
      seemed to be included in group 1. Mechanisms of urinary protein leakage have been
      in great controvesies, and nowadays defects of slit-membrane protein are supposed
      to play important roles. In the middle of the 20th centuries, electron microscopy
      and renal biopsy technique were adopted in practical use. Since then, the
      treatment and research of nephrotic syndrome have been remarkably progressed.
      Clinical strategies including diet therapy, immuno-suppressive and
      antihypertensive drugs and other modalities have improved the prognosis of
      nephrotic syndrome.

PMID- 15500118
TI  - [Nephrotic syndrome: pathophysiology, classification and diagnostic criteria].
AB  - The nephrotic syndrome is defined by heavy proteinuria due to abnormal increase
      of glomerular permeability and following hypoalbuminemia, hyperlipidemia and
      edema. Disorders of size selective barrier, charge selective barrier, slit
      diaphragm and circulating permeability factors are thought to be the causes of
      proteinuria. Most patients with nephrotic edema have primary salt retention.
      Overproduction and impaired catabolism of lipoproteins are the causes of
      hyperlipidemia. Abnormality of coagulation factors is also associated with
      nephrotic syndrome. Nephrotic syndrome may be primary or secondary to systemic
      disorders. Once diagnosed, the cause for the nephrotic syndrome must be examined.

PMID- 15500119
TI  - [Epidemiology of nephrotic syndrome].
AB  - Causes of nephrotic syndrome are varied with age, the times, geographical
      location and race. In children, minimal change nephrotic syndrome (MCNS) is
      common; however, membranous nephropathy (MN) is most frequent in adult. Incidence
      of membranoproliferative glomerulonephritis (MPGN) is decreased in advanced
      nations, although it remains a common in developing countries. In advanced
      nations, incidence of focal and segmental glomerular sclerosis (FGS) is
      increased, particularly in black populations. In Japan, MCNS was most frequent
      (37.7%), and then, MN was 23.3%, FGS was 7.2% and MPGN was 8.3% by a former
      research (in 1985). The recent research (in 1994) showed that MCNS was 41.5%, and
      next MN was 24.7%. FGS was increased to 11.8% and MPGN was decreased to 4.9%.

PMID- 15500120
TI  - [Refractory nephrotic syndrome].
AB  - In Japan, refractory nephrotic syndrome is defined as a pathological condition
      resistant to the treatment using corticosteroids and other immunosuppressive for
      6 months or more. The Research Group on Progressive Renal Disease sponsored by
      the Ministry of Health Labor and Welfare of Japan reported that 10 to 12% of the
      cases with idiopathic nephrotic syndrome were classified into this type and that
      the most common cause in adults is idiopathic membranous nephropathy (40%) and
      the second is focal segmental glomerulosclerosis (20%). In these conditions, less
      than 10% progressed to end stage renal disease (ESRD) when urine protein
      decreased under 1 g/day by the treatment. Persistent proteinuria is not only a
      marker of irreversible glomerular lesions but also a risk factor for
      tubulointerstitial lesions, which plays a significant role in progression into
      ESRD.

PMID- 15500121
TI  - [Responsible genes for proteinuria and concept of the treatment for proteinuria].
AB  - Proteinuria has been demonstrated to be not only a representative sign of renal
      lesion but also a risk factor for the progression to renal failure through its
      injurious effects on tubulointerstitium. The responsible gene for Finnish type
      congenital nephrotic syndrome was identified and its product was named 'nephrin'
      which is located on slit membrane between foot processes of glomerular epithelial
      cells and is considered to be concerned also in the induction of acquired renal
      lesions with proteinuria. The monoclonal antibody against rat nephrin can induce
      proteinuria. These facts suggest that the important role for final barrier
      against macromolecules is played by the slit membrane. Understanding the
      proteinuria mechanism at molecular level is expected to lead to the establishment
      of appropriate treatments. Nephrin is regarded as the most promising and
      attractive molecule for the development of new therapeutic strategy. Many
      nephrologists are now much interested in the intimate relationship between
      nephrin and angiotensin II.

PMID- 15500122
TI  - [Podocyte injury and glomerular sclerosis].
AB  - Recently, our understanding of podocytes has been greatly advanced by genetic
      analysis of human kidney diseases and corresponding animal models, establishment
      of podocyte cell lines, and discovery of podocyte specific promoters that
      facilitate transgenic research. Accumulating data indicate that podocyte injury
      initiates the process of the disease progression to glomerular sclerosis, a
      hallmark of chronic renal failure. In the progression to glomerular sclerosis,
      damages that initially affect only podocytes propagate to mesangial cells,
      glomerular endothelial cells and parietal epithelial cells. However, the
      mechanism underlying the propagation of injury from podocytes to other glomerular
      cells is largely unknown. Several recent topics regarding the mechanism of
      podocyte injury are also discussed.

PMID- 15500123
TI  - [Gene polymorphisms of renin-angiotensin system in patients with kidney
      diseases].
AB  - Blockade of the renin-angiotensin system (RAS), such as angiotensin-converting
      enzyme inhibitor and/or angiotensin receptor blocker, has been well appreciated
      as a renoprotective treatment in proteinuric glomerular diseases. However, not
      all patients with glomerular diseases respond well to this therapy. Single
      nucleotide polymorphisms (SNPs) in angiotensin-converting enzyme (ACE) and
      angiotensinogen may be involved in the inter-individual difference in the
      responsiveness to the renoprotective efficacy of the RAS blockade. This review
      focuses on the interface between genomics and therapeutics in the renin
      angiotensin system in IgA nephropathy, the most prevalent form of primary
      glomerulonephritis and one of the major causes of end-stage renal disease in the
      world.

PMID- 15500124
TI  - [Mitochondrial dysfunction and focal segmental glomerular sclerosis].
AB  - Focal segmental glomerular sclerosis (FSGS) is known as one of major renal
      complication of mitochondrial cytopathies. Glomerular epithelial cells are
      primary pathogenic sites in FSGS lesions. Glomerular epithelial cells are
      regarded as terminally differentiated cells and do not proliferate. This
      characteristic is the same for neuron cells and muscular cells, which are major
      sites of mitochondrial DNA mutations accumulation. Accumulation of mitochondrial
      DNA mutations might induce mitochondrial dysfunction and lead to FSGS lesion in
      glomeruli or these accumulations are only consequences of pathogenic stimuli to
      glomerular epithelial cells during the disease course of several
      glomerulopathies. Further investigations are needed to clarify pathogenic role of
      mitochondria and mitochondrial DNA mutations.

PMID- 15500125
TI  - [Novel functional molecules of slit membrane].
AB  - Several recent studies have shown that slit membrane (slit diaphragm) located
      between foot processes of glomerular epithelial cells plays the critical role for
      maintaining the barrier function of glomerular capillary wall. In 1998, nephrin
      was identified and was reported to be a critical component of the slit membrane.
      Following nephrin, several slit membrane-associated molecules were identified.
      Podocin was identified as a gene product of NPHS2, a mutated gene in patients
      with autosomal recessive steroid-resistant nephrotic syndrome. The studies with
      knockout mice showed that CD2AP and NEPH1 were also functional molecules in the
      slit membrane. It is reported that podocin interacts with nephrin and CD2AP, and
      that NEPH1 interacts with nephrin. These studies indicated that the precise
      arrangement and the interaction of these molecules are essential for maintaining
      the barrier function of slit membrane.

PMID- 15500126
TI  - [Minimal change nephrotic syndrome].
AB  - In minimal change nephrotic syndrome (MCNS), selective proteinuria is associated
      with structural alterations of the glomerular epithelial cells, such as
      effacement of the foot process. Although the pathogenesis of MCNS has not been
      completely clarified, clinical and experimental observations suggest that it
      results from T cell dysfunction in the pathogenesis. Recently, it has been
      proposed that the occurrence of MCNS has been associated with type 2 Th (Th2)
      lymphocyte-dependent conditions and some vascular permeability factors, which are
      induced by T cell disorder. In general, MCNS has the good long-term outcome with
      sustained remission and preserved renal function, because almost cases are
      responsible for the treatment. However, some patients show frequent relapses or
      resistance to this treatment and need large doses of immunosuppressive agents for
      a long time. Therefore, we should be care for the complications associated with
      prolonged these therapies.

PMID- 15500127
TI  - [Focal segmental glomerulosclerosis].
AB  - Focal segmental glomerulosclerosis (FSGS) is one of the major causes of nephrotic
      syndrome in adult as well as in the children. Untreated or steroid-resistant
      primary FSGS often shows a progressive renal insufficiency and reaches to end
      stage renal failure. Concerning the treatment for such patients, the combined
      immunosuppressive therapy with corticosteroid and other cytotoxic drugs
      (cyclophosphamide, cyclosporine and tacrolimus etc.) is recommended. Since
      podocyte injury seems to be the most important primary events in FSGS, the
      extensive studies have been focused on the role of podocyte-related molecules.
      Recently slit membrane-associated molecules (CD2AP, alpha-actinin 4 and podocin)
      and angiotensin II type I receptor in the podocyte have been clearly shown to be
      relevant for the pathogenesis of FSGS.

PMID- 15500128
TI  - [Mesangial proliferative glomerulonephritis].
AB  - IgA nephropathy is by far the most popular mesangial proliferative
      glomerulonephritis which can induce nephrotic syndrome. The etiology and
      pathogenesis of IgA nephropathy are still elusive, however. The enigma is that
      the IgA molecules deposited in glomeruli are mainly IgA1 subclass produced in
      central lymphoid organs and not the IgA2 subclass produced in peripheral mucous
      membrane, contrary to the notion that mucosal defense mechanism may be
      exacerbated in patients with IgA nephropathy. Recent investigations have
      elucidated that clearance of IgA might be deteriorated in these patients due to
      the abnormalities in the O-glycosylation of the hinge region of IgA molecules.
      The etiopathogenesis of IgA nephropathy elucidated in recent years is discussed.

PMID- 15500129
TI  - [Membranoproliferative glomerulonephritis].
AB  - MPGN is characterized by its peculiar histological findings; lobular appearance,
      cellular and mesangial matrix proliferation and double contoured capillary loops.
      Based on histomorphalogical pattern, three types are subdivided. MPGN may be
      primary (in most children) or secondary (in most adults) to chronic infections,
      cryoglobulinemia or systemic autoimmune disorders. Clinical manifestation of
      typical MPGN is nephrotic range proteinuria associated with microscopic
      hematuria, showing slowly progressive course. Treatment strategy is composed of
      exclusion of pathogen, especially in HCV positive MPGN, and intervention to
      autoimmune mechanism such as alternative-day steroid regimen.

PMID- 15500130
TI  - [Membranous nephropathy].
AB  - Membranous nephropathy (MN) is a frequent cause of nephrotic syndrome in adults.
      A considerable diversity of prognosis is seen with idiopathic MN. We overview the
      recent progress of clinicopathological research, especially the initial factors
      affecting the longterm outcome of idiopathic MN. We studied retrospectively 105
      patients with idiopathic MN and could assign the patients to two different groups
      based on the electron microscopic (EM) findings. In the homogeneous type only one
      patient developed end-stage renal failure, and earlier remission occurred in this
      group. With regard to secondary outcome, increased age, focal segmental
      glomerular sclerosis, arteriolosclerosis, heterogeneous type of EM findings were
      independent risk factors. Our results suggest that a new EM classification at
      initial biopsy is an independent indicator of prognosis in human idiopathic MN.

PMID- 15500131
TI  - [Congenital nephrotic syndrome].
AB  - Although congenital nephrotic syndromes (CNS) form a heterogenous group of
      disease characterized by proteinuria shortly after birth, the most common type of
      CNS is the congenital NS of the Finnish type (CNF). CNF is an autosomal recessive
      disease, and caused by mutations in the gene (NPHS1) for nephrin which is a key
      component of the podocyte slit diaphragm. In this review, some special issues
      concerning clinical and molecular diagnosis for CNS and optimal management of CNF
      patients were briefly summarized.

PMID- 15500132
TI  - [Corticosteroid therapy for nephrotic syndrome].
AB  - Although the cause of primary nephrotic syndrome remains unclear, the progress of
      basic science has indicated that immune T cell disorders lead to glomerular
      dysfunctions. Patients with primary nephrotic syndrome and some of secondary
      nephrotic syndrome are, thereby, initially treated with high dose of
      corticosteroids. Steroid responsiveness is an important prognostic indicator of
      the disease, and in steroid-resistant patients, immunosuppressive agents and the
      methylprednisolone pulse therapy are recommended. Although a treatment based on
      corticosteroids has brought about clinical benefits, several adverse effects,
      including various opportunistic infections, osteoporosis/bone fracture, aseptic
      necrosis of femoral head, and so on, are frequent and sometimes severe and
      suitable preventions and urgent treatments are prerequisite in such patients.

PMID- 15500133
TI  - [Immunosuppressive therapy for nephrotic syndrome and strategy for adverse side
      effects from that therapy].
AB  - The nephrotic syndrome is commonly caused by various glomerulonephritides, i.e.
      minimal change nephrotic syndrome, focal segmental glomerulosclerosis and
      membranous nephropathy. A long term corticosteroid therapy is a first therapeutic
      approach for patients with nephrotic syndrome. In patients who have
      contraindication to steroids or in those who do not respond to steroids,
      immunosuppressive agents such as cyclosporine, mizoribine, azathioprine and
      cyclophosphamide are the next therapeutic approach for inducing the remission of
      the nephrotic syndrome. In this review, we described an appropriate use of
      systemic immunosuppressive agents for steroid resistant nephrotic syndrome, and
      the toxicity and side effects of each agent. And currently the clinical trials
      with new immunosuppressants like tacrolimus (FK 506) and mycophenolate mofetil
      are also described.

PMID- 15500134
TI  - [RAS blockade].
AB  - Angiotensin II (AII), the biologically active component of renin-angiotensin
      system (RAS), acts through two receptor subtypes, the AT1 and AT2 receptor. All
      classic physiological effects of AII, such as vasoconstriction, aldosterone and
      vasopressin release, sodium and water retention and sympathetic facilitation, are
      mediated by the AT1 receptor. The majority of pilot studies demonstrated the
      renoprotective effect of RAS blockers via antihypertensive, antiproteinuric,
      antifibrotic action. In order to establish whether RAS blocker causes
      antiproteinuric effects or long-term renoprotection in the non-diabetic nephrotic
      disease, larger prospective, randomized controlled trials are required in the
      future.

PMID- 15500135
TI  - [Lifestyle modification and diet therapy for nephrotic syndrome].
AB  - The management of the lifestyle of patients with nephrotic syndrome is important
      to prevent progression to end stage renal failure. In spite of various kinds of
      medication, the daily lifestyle and diet modification should be taken into
      consideration from the early stage. The strict restriction of exercise is
      disagreeable. However, when exercises have bad influence on the renal function,
      we need to restrict exercise suitably. Optimal dietary protein intake is 1.0-1.1
      g/kg/day in minimal change nephrotic syndrome and 0.8 g/kg/day in other types of
      nephrotic syndrome. Additional protein restriction should be required for
      patients with renal dysfunction. Energy requirements are basically more than 35
      kcal/kg/day. Salt should not be rigidly restricted and 5-7 g/day of salt may be
      permitted in the steady state. Moreover, the nutrition state should be evaluated
      by physical measurements and laboratory data, and workmanship of diet therapy
      should be guided.

PMID- 15500136
TI  - [Prevention and management of complications in nephrotic syndrome].
AB  - Nephrotic syndrome is defined as the glomerular disease with massive proteinuria
      and hypoalbuminemia, and complications are numerous. Among these complications,
      saltwater retention, thromboembolism, hyperlipidemia, metabolic bone disease,
      infections are important for management of nephrotic syndrome. Recent advances in
      the understanding of alterations in the metabolism of circulating and somatic
      proteins associated with proteinuria and hypooncotic condition have led to new
      insights into the pathophysiologic processes associated with this syndrome.
      Therapeutic consideration should be paid not only for the treatment of primary
      diseases, but also for the prevention of these complications.

PMID- 15500137
TI  - [Secondary nephrotic syndrome due to collagen disease and vasculitis].
AB  - The most frequent and representative nephrotic syndrome associated with collagen
      disease is encountered in patients suffering from lupus nephritis. Lupus
      nephritis is a glomerulonephritis, which discloses various localizations of
      immune complexes in the endothelium, mesangium and subepithelium. In addition,
      vasculitides complicated by nephrotic syndrome also show the deposition of immune
      complexes in their glomeruli, such as Henoch-Schonlein nephritis and
      cryoglobulinemic nephritis. The pathogenetic mechanisms of these nephrotic
      syndromes are explained as follows. The depositions of immune complexes in
      glomeruli causes proteinuria through a variety of mechanisms. Namely,
      subendothelial and mesangial immune deposits give capillary and mesangial
      injuries as well as inflammation that are mediated through activation of
      complements and cytokines, and subsequently leads to nephrotic-range proteinuria
      and impairment of renal function. On the other hand, subepithelial and
      intramembranous deposits disrupt the regulated arrangement of epithelial cells
      and slit diaphragms, and then disturb the slit diaphragms. The eventual
      dysfunction of slit diaphragms accordingly progresses to massive proteinuria even
      without capillary injury. Therefore, nephrotic syndrome associated with collagen
      disease or vasculitis is usually observed in lupus nephritis or vasculitis
      related to immune complex depositions, but is not observed in non-immune complex
      glomerulopathy or vasculopathy.

PMID- 15500138
TI  - [Nephrotic syndrome due to metabolic disease--special reference to diabetic
      nephropathy].
AB  - Diabetes has become the most common single cause of end stage renal disease.
      Nephrotic syndrome is often manifested in the progression of diabetic
      nephropathy. Diabetic nephropathy has several pathways for development, such as
      glomerular hyperfiltration, upregulation of protein kinase C, advanced glycation
      end products, activation of polyol pathway, increased oxidative stress and
      upregulation of growth factors. Intensive control of blood pressure and the use
      of angiotensin converting enzyme inhibitor or angiotensin receptor blocker can
      protect the progression of nephropathy with nephrotic syndrome. However further
      studies are necessary for the clinical guidline in patients with diabetic
      nephropathy manifesting with nephrotic syndrome.

PMID- 15500139
TI  - [Nephrotic syndrome and malignancy].
AB  - The patients with nephrotic syndrome frequently associate with solid tumors as
      well as hematologic malignancies, although the presence of nephrotic syndrome in
      patients with malignancy is rare. The association cannot be explained by chance
      alone, because it occurs at a rate. Theoretically, malignancy-associated
      glomerulopathy should be explained by at least two clinical criteria. First, a
      remission of proteinuria achieves after surgical removal of tumor or
      disappearance of tumor by chemotherapy. Second, relapse of proteinuria occurs
      after recurrence of malignancy. However, pathophysiologic link which is the third
      important criteria has not been established between the two diseases.

PMID- 15500140
TI  - [Drug induced nephrotic syndrome].
AB  - This review summarizes drug induced nephrotic syndrome. Major drugs which induce
      drug related nephrotoxicity are antibiotics, NSAID, radiocontrast media,
      anticancer drug and antirheumatic drug. Drug induced nephropathy can show various
      forms of renal diseases. The nephropathy consists of acute tubular necrosis,
      acute tubulointerstitial nephritis, pre-renal type renal failure, obstructive
      renal failure, chronic tubulointerstitial nephritis and glomerular damage. Major
      drugs which induce nephrotic syndrome and glomerular damage are gold,
      penicillamine, bucillamine and NSAID. In the nephrotic syndrome due to these
      drugs, the major type of renal disease is the membranous glomerulonephritis and
      the nephropathy resolves completely when the drug is withdrawn; renal function
      does not deteriorate, and corticosteroids are unnecessary.

PMID- 15500141
TI  - [Secondary nephrotic syndrome induced by infection].
AB  - Infections can be the causative agent in secondary nephrotic syndrome and
      diagnostic criteria include clinical and laboratory data and tissue molecular
      analysis. As for bacterial infections, some of patients with poststreptococcal
      glomerulonephritis or methicillin-resistant Staphylococcus aureus-related
      glomerulonephritis present nephrotic syndrome. Hepatitis B virus (HBV) is a well
      known cause of membranous glomerulonephritis and membranoproliferative
      glomerulonephritis. Hepatitis C virus (HCV), besides cryoglobulinemia-mediated
      glomerulonephritis, is reported to cause other forms of glomerulonephritis. Human
      immunodeficiency virus (HIV) infection is closely related to a collapsing focal
      segmental glomerulonephritis. Some of patients with these viral infections
      present nephrotic syndrome. There were a few reports on secondary nephrotic
      syndrome induced by cytomegalovirus, Epstein-Barr virus and parvovirus B19.

PMID- 15500142
TI  - [Secondary nephrotic syndrome due to cardiovascular disease].
AB  - Cardiovascular diseases ralely evoke nephrotic syndrome. Especially hypertensive
      renal disease (nephroscrelosis) and renovascular hypertension occasionally may
      lead to nephrotic syndrome. We reported a case of nephrotic syndrome with
      renovascular hypertension successfully treated with candesartan. In eldery
      patients cardiovascular diseases are appeared. It is very important for
      clinicians to detect the mechanism of nephrotic syndrome caused by cardiovascular
      diseases.

PMID- 15500143
TI  - [Secondary nephrotic syndrome due to preeclampsia].
AB  - Severe preeclampsia is sometimes associated with nephrotic syndrome. As
      pathological finding of kidney in preeclampsia, the endotheliosis in glomerulus
      and focal segmental glomerulosclerosis have been described. These findings
      disappear frequently within 40 days after delivery. Proteinuria is originated
      from the damage of charge and pore selectivity. Some immunological changes such
      as presence of autoantibodies and Th1 predominance have been reported in
      preeclampsia. In preeclampsia with proteinuria, high incidence of intrauterine
      growth retardation is found. In preeclamptic patients with proteinuria of greater
      than 5 g/24 hour, perinatal mortality rate becomes high. When the preeclamptic
      patients have hematuria or high titer of serum IgA, renal diseases are frequently
      complicated with preeclampsia.

PMID- 15500144
TI  - [Role of interleukin-5 in immune regulation and inflammation].
AB  - IL-5 is produced mainly by activated Th2 and mast cells. High level of IL-5 mRNA
      expression is detected in c-kit- cells in the lung, spleen, stomach and small
      intestine in RAG2-/- mice, suggesting the IL-5 production by non-T/non-mast/non
      eosinophils. The IL-5R consists of two distinct membrane proteins, IL-5Ralpha and
      betac. The binding of IL-5 occurs through the IL-5Ralpha, and the betac forms a
      high-affinity IL-5R in combination with the IL-5Ralpha and transduces signals
      into nuclei. Activation of Btk and Jak2 kinases, rapid tyrosine phosphorylation
      of betac, adaptor proteins and transcription factors STAT5; and inductions of
      transcription of several nuclear proto-oncogenes are essential for the IL-5
      signal transduction. Transgenic mice expressing the IL-5 gene exhibit elevated
      levels of serum IgM, IgA and IgE, increase in numbers of B-1 cells and
      eosinophils, and show persistent eosinophilia. Functional analysis of the IL
      5Ralpha-/- and IL-5-/- mice revealed that IL-5 plays critical roles in the
      homeostatic proliferation, cell survival and activation of mature B-1 cells and
      regulates IgA production in the mucosal tissues in response to LPS. We also found
      that IL-5 can induce mu to gamma1 class-switch recombination in activated B-2
      cells by activating AID and Blimp-1. Taking together, IL-5 plays important roles
      in terminal differentiation of B-lineage cells. In humans, IL-5 preferentially
      acts on eosinophil precursors and mature eosinophils to prolong maturation,
      survival and activation. Humanized anti-IL-5 mAb treatment for asthmatic patients
      was shown to reduce 100% for blood eosinophils but does not deplete airway or
      bone marrow eosinophils. No significant changes in airway hyper-responsiveness
      and peak flow recordings between the anti-IL-5 and placebo-treated groups were
      reported. At this moment, the role of IL-5 and eosinophil in allergic
      inflammation remains uncertain.

PMID- 15500145
TI  - [False negative cases of F-18 fluorodeoxyglucose-positron emission tomography
      (FDG-PET) imaging in small lung cancer less than 3 cm in size].
AB  - A considerable number of false negative cases in FDG-PET were seen in small-cell
      lung cancer, despite the usefulness of this imaging modality. We investigated the
      correlation between FDG-PET results and the clinicopathological findings in small
      lung cancers less than 3 cm in size. Fifty-one consecutive cases of surgically
      resected small lung cancers scanned preoperatively by FDG-PET was assessed. The
      medical records of each case were reviewed for the maximum tumor size in the CT
      findings, histology, grade of differentiation, lymphatic and vascular invasion,
      pleural invasion, lymph node stage, serum level of carcinoembryonic antigen
      (CEA), and CT findings. All of the 5 cases (4 adenocarcinomas, 1 small-cell
      carcinoma) less than 1 cm in size were false negatives. In the 46 cases 1-3 cm in
      size (34 adenocarcinomas, 9 squamous sell carcinomas, 2 large sell carcinomas, 1
      small cell carcinoma), false negative results were seen in 8 of 15 cases of well
      differentiated adenocarcinoma (53%). In the 8 false negative cases, 1 (13%)
      lymphatic vessel invasion (ly), 0 (0%) vascular vessel invasion (v), 0 (0%)
      pleural invasion (p), 0 (0%) lymph node metastasis, 0 (0%) high serum level of
      CEA, and 5 (63%) cases showing ground-glass opacity on CT were observed. There
      were significant differences in the factors ly, v, CEA, and CT findings between
      the 8 false-negative cases and the 26 true positive cases with adenocarcinoma (p
      < 0.01-0.05). Lung cancers < 1 cm in size cannot be detected in FDG-PET.
      Adenocarcinomas of the lung 1-3 cm in size with false negatives in FDG-PET showed
      significantly less invasiveness than the true positives.

PMID- 15500146
TI  - [Clinical evaluation of portable overnight sleep respiration graph for diagnosis
      of sleep apnea syndrome].
AB  - Recently, a noninvasive medical device (SD-101) capable of detecting breathing
      pattern changes in a subject lying supine or on the side has been developed. We
      therefore tested whether the SD-101 would be useful for diagnosing sleep apnea
      syndrome (SAS). Seventy patients who had been suspicious of SAS were enrolled
      (M/F = 61/9, mean age +/- SD = 46.6 +/- 14.7 y/o). They took 2 distinct screening
      tests for SAS (using the SD-101 and one of the most popular screeners for SAS in
      Japan (Apnomonitor III: AP, Chest Co., Tokyo)) and a simultaneously performed
      standard polysomnography (PSG). All patients were then asked to respond to a
      questionnaire on awareness of invasiveness experienced during each study (both
      from the screeners and from the standard PSG). The data were then compared with
      those from PSG mainly using correlation coefficients and the x2 test for analysis
      of subjective invasiveness. Statistical significance was defined as a p value of
      less than 0.05. As a result, the apnea-hypopnea index (AHI) from SD-101 (r=0.947,
      p<0.0001) had a significantly higher correlation coefficient (p<0.0001) than that
      from the AP (r=0.601, p<0.0001) in relation to that from PSG. The SD-101 had a
      significantly lower invasiveness than either AP or PSG (p<0.0001). In conclusion,
      SD-101 could be much more useful for checking AHI than other conventional
      screeners, such as AP, which suggests that SD-101 is more useful for defining
      SAS.

PMID- 15500147
TI  - [A national survey of results of lung volume reduction surgery (LVRS) for
      pulmonary emphysema in Japan].
AB  - We made a national questionnaire survey of conditions and results of lung volume
      reduction surgery (LVRS) performed for pulmonary emphysema in 273 hospitals. The
      survey covered: number of hospitals, number of patients, indications, operative
      procedures, improvement of FEV1% and dyspnea score, mortality, cause of death, 5
      year survival rate, characteristics of patients who died, and current conditions
      of LVRS. The response rate was 63%. A total of 619 patients at 41 hospitals
      underwent LVRS. The most common types of surgical procedure were bilateral LVRS
      through median sternotomy and unilateral LVRS with video-assisted thoracoscopic
      surgery (VATS), followed by bilateral LVRS with VATS. Postoperative improvement
      in FEV1% averaged 39%. Dyspnea improved in 80% of patients. Mortality rate was
      1.9% (8 of 432 cases). Postoperative infectious diseases, namely pneumonia and
      sepsis, were common causes of death. The 5-year survival was 65 +/- 8%. The
      causes of death over 5 years were respiratory failure in 60%, malignant neoplasms
      in 17%, cardiovascular accidents in 13% and others in 10%. The number of
      operations and hospitals decreased in 2002, compared to 2001.

PMID- 15500148
TI  - [Pulmonary infection with Nocardia species: a report of 10 cases].
AB  - OBJECTIVE: To investigate the clinical features of pulmonary nocardiosis.
      PATIENTS AND METHODS: We retrospectively reviewed ten consecutive patients (5
      men, 5 women; aged 25 to 80 years (average 49.3 years)) with confirmed
      bacteriological pulmonary nocardiosis from 1998 to 2003. Patients were divided
      into two groups: infected (8 patients) and isolated (2 patients). RESULTS: All
      patients had predisposing factors and/or pulmonary disease. Six were
      immunosuppressed by steroid therapy with or without other immunosuppressive
      drugs. The overall survival rate among infected patients was 75.0% (6/8), but the
      survival rate of patients who were diagnosed speedily by a gram-stain procedure
      was 85.7% (6/7). CONCLUSIONS: Although pulmonary nocardiosis is difficult to
      diagnose, prompt use of the gram-staining procedure and appropriate treatment
      appeared to improve survival. And new diagnostic method is desirable.

PMID- 15500149
TI  - [A case of microscopic polyangitis presented with acute pericarditis].
AB  - We report a case of microscopic polyangitis presenting with acute pericarditis. A
      75-year-old man, who had recurrent acute pericarditis, was referred by a
      cardiologist because of bilateral infiltrates in the chest radiograph,
      microhematuria and progressive renal failure. The test for MPO-ANCA was positive.
      Transbronchial and renal biopsies were compatible with microscopic polyangitis,
      showing alveolar hemorrhage and crescentic glomerulonephritis. After 3 days,
      intravenous methylpredonisolone was given, followed by oral prednisolone 40
      mg/day, and the patient's radiographic infiltrates cleared and renal dysfunction
      improved. However, he died from opportunistic infection 109 days after the onset
      of treatment.

PMID- 15500150
TI  - [A case of cT0N2M0 small cell lung cancer with Lambert-Eaton myasthenic
      syndrome].
AB  - We encountered a very rare case of cT0N2M0 small cell lung cancer (SCLC) with
      Lambert-Eaton myasthenic syndrome (LEMS). A 69-year-old man with a complaint of
      muscle weakness was admitted to our hospital. Although his chest radiograph on
      admission showed no abnormal findings, CT scanning detected a mediastinal
      lymphadenopathy. Also, 2-[18F]-2-fluorodeoxy-D-glucose position emission
      tomography (FDG-PET) revealed increased accumulation in the same portion in the
      mediastinum. A diagnosis of LEMS was made from the distinctive electromyogram
      (EMG) findings (waning and waxing phenomenon in response to low-and high
      frequency repetitive stimulation, respectively) in combination with the increased
      serum level of a P/Q-type anti-voltage-gated calcium channel (VGCC) antibody.
      Subsequent histopathological diagnosis by mediastinoscopic resection of a
      paraaortic lymph node was small cell carcinoma. No distant metastasis was
      detected by MRI of the brain, abdominal CT scan or an FDG-PET. Eight courses of
      chemotherapy (carboplatin + etoposide) with radiotherapy of the mediastinum (for
      a total dose of 45 Gy) was performed. A decreased serum level of P/Q-type anti
      VGCC antibody titers followed by marked improvement of neurological dysfunction
      (muscle weakness, gait disturbance and scanning speech) and of an EMG finding (a
      loss of waning phenomenon) was observed. A close relationship between reduction
      of the antibody titers and improvement of neurological symptoms after the therapy
      was noticed. It was suggested that monitoring the level of a P/Q-type anti-VGCC
      antibody titer in the serum is important for evaluating the efficacy of
      chemotherapy for LEMS associated with SCLC.

PMID- 15500151
TI  - [Treatment of pulmonary amyloidosis with dimethyl sulfoxide--a case report].
AB  - Metastatic lung tumor was suspected in a 52-year-old woman who showed multiple
      nodules on her chest radiographs. Conventional examinations did not define the
      diagnosis, and so a biopsy was performed using video-assisted thoracoscopic
      surgery. Pathological examination demonstrated deposits of amorphous materials
      which were stained red by Congo red staining, even after potassium permanganate
      treatment. Green birefringence was also observed in the deposits under a
      polarized light microscope. A diagnosis of localized pulmonary amyloidosis with
      AL type amyloid protein was made, and therapy with dimethyl sulfoxide (10 ml/day)
      was started. During the two-year therapy, little exacerbation on pulmonary
      nodules was observed. It was suggested that dimethyl sulfoxide inhibited the
      progression of the disease.

PMID- 15500152
TI  - [A case of pulmonary Mycobacterium intracellulare infectious disease with a
      solitary pulmonary nodule in the peripheral lung field].
AB  - A 63-year-old woman was admitted to our hospital because of a solitary nodule (20
      x 20 mm) in the right S3 which was first detected during a health examination.
      Because radiological findings for the nodule, such as pleural indentation and
      spicula on chest CT led us to suspect a pulmonary adenocarcinoma, we could not
      completely rule out lung cancer and performed a bronchoscopic examination on the
      third day after admission. However, no definite diagnosis could be made.
      Therefore, video-assisted thoracic surgery (VATS) was performed, and a caseating
      epitheloid granuloma with acid-fast bacilli was found. Initially, we administered
      antituberculous drugs for pulmonary tuberculoma, but then changed to combined
      chemotherapy using RFP, EB, CAM and SM after identification of Mycobacterium
      intracellulare by a culture test of resected tissue. We report a rare case with a
      solitary nodule caused by pulmonary Mycobacterium intracellulare infectious
      disease which is indicative of lung cancer.

PMID- 15500153
TI  - [A case of idiopathic bronchiolitis obliterans accompanied with pneumothorax and
      pulmonary atypical mycobacteriosis].
AB  - A 22-year-old man was urgently admitted for pneumothorax. He continued
      complaining of exertional dyspnea and dry cough after the pneumothorax healed.
      About three months later, an atypical pulmonary mycobacteriosis by mycobacterium
      kansasii was identified. Exertional dyspnea increased after chemotherapy was
      administered, and the patient was readmitted because of difficulty in daily life
      activities. Chest radiographs and CT scans showed bilateral pulmonary
      hyperinflation and a narrowed heart shadow. There was also marked combined
      ventilatory impairment, as identified by a respiratory function test.
      Furthermore, the histological findings of surgically removed lung tissue revealed
      accumulation of lymphocytes in the wall of a small bronchus. Idiopathic
      bronchiolitis obliterans was diagnosed from the clinical course and clinical
      findings. The patient is now being monitored and is awaiting lung
      transplantation.

PMID- 15500154
TI  - [A case of allergic granulomatosis and angiitis (Churg-Strauss syndrome) in a 15
      year-old girl].
AB  - A 15-year-old girl with a 6-month history of bronchial asthma was admitted to our
      hospital because of fever, dyspnea, weight loss, dysesthesia, muscle weakness,
      gait disturbance and purpuric rash. In addition, leukocytosis, hypereosinophilia
      and elevation of CRP were observed. Chest radiograph and computed tomography on
      admission showed non-segmental patchy air-space consolidation in both lung
      fields. Skin biopsy was performed and the pathologic diagnosis was necrotizing
      arteritis with eosinophilic infiltration. Transbronchial lung biopsy revealed
      eosinophilic pneumonia. From the clinical course, laboratory data and pathologic
      findings, the diagnosis of allergic granulomatosis and angiitis (Churg-Strauss
      syndrome) was made. Following the skin and lung biopsies, intravenous pulse
      corticosteroid and oral prednisolone treatment was started and her clinical
      findings improved. Angiitis with allergic granulomatosis is a vasculitis that is
      found in adults. This is an extremely rare and interesting case of angiitis with
      allergic granulomatosis in childhood.

PMID- 15500155
TI  - [A case of anhidrotic ectodermal dysplasia diagnosed during investigation of
      asthmatic attack].
AB  - A 24-year old man was hospitalized because of a severe asthmatic attack in August
      2003. The asthma attack was well controlled by mechanical ventilation,
      intravenous hydrocortisone and inhaled beta2-agonist. Physical examination
      revealed sparse hair, reduced sweating and hypodontia. We also confirmed the
      absence of sweat glands in a biopsied skin specimen. The diagnosis based on these
      findings was anhidrotic ectodermal dysplasia A mutation in the EDA (ectodysplasin
      A) gene which led to an X-linked anhidrotic ectodermal dysplasia was found, and
      the same genetic mutation was detected in the patient's mother.

PMID- 15500156
TI  - [A case of pulmonary aspergillosis with bone invasion and destruction in an AIDS
      patient].
AB  - A 59-year-old HIV-infected man who had been treated for pulmonary cryptococcosis
      in another hospital was suffering from pulmonary tuberculosis. He was admitted to
      our hospital for treatment of tuberculosis. The chest radiograph on admission
      showed a large cavity in the left lower lung field. Chest CT showed a mass like a
      fungus ball in the cavity. Pulmonary aspergillosis was diagnosed from the sputum
      mycology and serum immunoprecipitins. During the treatment of pulmonary
      tuberculosis and cryptococcosis, thickening of the wall of the cavity was seen
      together with adjacent bone destruction. In an autopsy, Aspergillus spp. Were
      found to have invaded the bone tissue and caused bone destruction. Pulmonary
      aspergillosis in an AIDS patient is infrequent, and is rare in additional
      association with bone invasion and destruction.

PMID- 15500157
TI  - [Two cases of lung cancer in the third decade of life].
AB  - We report two cases of lung cancer in the third decade of life. One patient was a
      27-year-old man complaining of persistent cough and chest pain. He was referred
      for examination of an abnormal shadow found on chest radiography. A diagnosis of
      adenocarcinoma consisting of bronchial gland cells was made by bronchial biopsy.
      The clinical stage was T4N2M1. Although he was treated with cisplatin-based
      chemotherapy and gefitinib, he died of lung cancer. The other patient was a 26
      year-old Chinese woman complaining of hemosputum. Since histologic examination at
      thoracotomy revealed lung cancer, left lower lobectomy and lymph node dissection
      were performed. Histological examination of the resected specimen revealed
      pleomorphic carcinoma. The pathological stage was pT2N2MX. Although the absolute
      number of young adults with lung cancer has been increasing, the relative
      incidence among all cases of lung cancer has been decreasing. In some cases,
      young adults with lung cancer have been misdiagnosed as having bronchial asthma
      or pulmonary tuberculosis.

PMID- 15500158
TI  - [What aspects are inefficient concerning percutaneous coronary intervention in
      Japan?: International cost-effectiveness comparisons].
AB  - OBJECTIVES: To investigate the outcome-cost relationship of percutaneous coronary
      intervention (PCI) during 1 year in Japan and other countries. Foreign databases
      showing similar coronary events to those observed in Japan during the follow-up
      period were chosen. METHODS: The Japanese multicenter prospective observational
      cost database (JSIC) was compared to the Stent Restenosis Study (STRESS), a
      university hospital (DUKE), Arterial Revascularization Therapies Study (ARTS),
      and the Primary Angioplasty in Myocardial Infarction trial (PAMI). The presence
      of acute myocardial infarction (AMI), implantation of stents, and number of
      involved coronary vessels are known to affect the costs of the initial
      hospitalization and during the follow-up period. The JSIC database was subdivided
      according to those factors and the initial hospitalization expenses and follow-up
      costs was compared. RESULTS: All foreign databases showed similar outcomes for
      coronary events (deaths or repeat PCI or bypass surgery)compared to the JSIC
      during the 1 year follow-up period. The cumulative costs for the non-AMI group in
      the JSIC, STRESS, DUKE, and ARTS were 23.1, 11.3, 22.2, and 10.7 thousand
      dollars, respectively, and for the AMI group were 27.6 and 20.1 thousand dollars
      in the JSIC and PAMI, respectively. Balloon catheter costs of initial
      hospitalization expenses accounted for 50% in JSIC, 23% in STRESS, 31% in DUKE,
      and 16% in PAMI, but the mean numbers of balloons and stents used per patient
      were similar. CONCLUSIONS: Costs for PCI were higher in Japan than in most other
      countries. The difference derived mainly from the higher costs of catheters, not
      from the longer hospital stay in Japan.

PMID- 15500159
TI  - [Surgical treatment of active infective endocarditis: analysis of 20 years'
      experience].
AB  - OBJECTIVES: Changes in perioperative condition and outcomes of surgically treated
      patients with active infective endocarditis were evaluated during the last 20
      years. METHODS: Between 1983 and 2002, 132 patients with active infective
      endocarditis underwent surgery at Saitama Medical School. Changes in frequency,
      pathogens, clinical features, surgical results, and perioperative treatment were
      compared between four periods of 5 years. RESULTS: The percentage of surgery for
      infective endocarditis remained almost the same among all cardiovascular
      procedures. Staphylococcal infective endocarditis increased significantly (p <
      0.01), and prosthetic valve infective endocarditis and periannular abscess became
      more common. Surgery tended to be performed in severely ill patients
      significantly more frequently (p < 0.01). If all patients were included, hospital
      mortality did not decrease significantly, at 1.7% in stable patients, but 50% in
      critically ill patients. Intensive care unit stay became relatively longer.
      Recurrent infection was observed significantly more frequently in critically ill
      patients and in patients with prosthetic valve infective endocarditis. Patients
      were referred for surgery following diagnosis and underwent surgery at
      increasingly more appropriate timing. However, the diagnosis of infective
      endocarditis took 1.5 months to establish regardless of the patient's condition
      or the clinical outcome. Moreover, antibiotics were administered orally in around
      90% and intravenously in nearly 70% of the patients without microbiological
      tests, and negative cultures remained very frequent. CONCLUSIONS: Critically ill
      patients underwent surgery increasingly more frequently, and surgical outcomes
      remained unsatisfactory over the last 20 years. Early diagnosis and avoidance of
      premature antibiotic therapy may be important for future improvement.

PMID- 15500160
TI  - Improved stratification of perioperative cardiac risk in patients undergoing
      noncardiac surgery using new indices of dobutamine stress echocardiography.
AB  - OBJECTIVES: Prediction of perioperative cardiac events associated with noncardiac
      surgery remains difficult in patients whose functional capacity cannot be
      evaluated by exercise testing. Dobutamine stress echocardiography (DSE) has been
      used in these patients to improve risk stratification, but the results of
      standard DSE provide only a binary index of risk (positive or negative). Two new
      semiquantitative indices of DSE (semi-DSE) were retrospectively examined to
      determine the prediction of perioperative cardiac events compared to standard
      DSE. METHODS AND RESULTS: Clinical assessment of cardiac risk factors and
      standard DSE were performed safely in 122 consecutive patients (73 men, 49 women)
      undergoing noncardiac surgery. Preoperative revascularization was performed in 12
      patients. The perioperative cardiac events consisted of 2 deaths, 4 cases of
      heart failure, and 2 cases of angina pectoris. For the semi-DSE indices, the
      extent of ischemia was indexed as the number of wall segments (SEG) displaying
      biphasic or worsening segmental wall-motion score, and the severity of ischemia
      (SI) was indexed as the sum of the differences in wall-motion scores between peak
      stress and rest divided by the number of affected segments. The optimal cut-off
      values of these indices for predicting cardiac events were 4.0 for SEG and 1.0
      for SI. The risk stratification was further refined by these indices (high-,
      moderate-, and low-risk groups). The diagnostic accuracy of the semi-DSE indices,
      evaluated by the area under the receiver operating characteristic curves, was
      better than that of standard DSE (p < 0.001). CONCLUSIONS: Semi-DSE may improve
      cardiac-event risk stratification compared to standard DSE in patients undergoing
      noncardiac surgery whose functional capacity cannot be evaluated by exercise
      stress testing.

PMID- 15500161
TI  - [Chordal cutting for the treatment of ischemic mitral regurgitation: two case
      reports].
AB  - The surgical treatment for ischemic mitral regurgitation remains controversal.
      Ring annuloplasty results in recurrent mitral regurgitation in some cases. Strut
      chordal cutting is a new surgical procedure in addition to ring annuloplasty for
      ischemic mitral regurgitation. Two patients (63-year-old woman, 53-year-old man)
      with severe ischemic mitral regurgitation were treated with this procedure. The
      patients had congestive heart failure due to mitral regurgitation, associated
      with inferior myocardial infarction. Regurgitant fraction of mitral regurgitation
      was 70% and 52% before surgery. Mitral leaflet tethering caused by apical
      displacement of the papillary muscle was observed. Mitral valve repair was
      performed by ring annuloplasty and chordal cutting. Intraoperative
      echocardiography showed that chordal cutting improved the configuration of the
      anterior leaflet, resulting in good mitral valve coaptation without
      regurgitation.

PMID- 15500162
TI  - [Pseudoaneurysm of the left ventricle following suppurative pericarditis and
      sepsis due to Staphylococcus aureus: a case report].
AB  - A 35-year-old diabetic man presented with a left ventricular aneurysm very close
      to the mitral valve annulus. He had been conservatively treated for suppurative
      pericarditis and sepsis due to Staphylococcus aureus during the previous 3 weeks.
      The left ventricular aneurysm rapidly enlarged (6 cm in diameter) and the patient
      underwent emergent surgery. Cardiopulmonary bypass and cardioplegic arrest were
      induced, and the left ventricular aneurysm orifice was closed with a double layer
      of autologous pericardium. Mitral valve function was not impaired. He has been
      doing well for 4 years. Surgery is indicated as soon as possible after the
      diagnosis of infective left ventricular aneurysm.

PMID- 15500163
TI  - [Abnormal fluorine-18 fluorodeoxy-glucose uptakes in the aorta and subclavian
      artery of a 66-year-old woman].

PMID- 15500164
TI  - [Anthropogenic sources of radiation hazard in the near-Earth space].
AB  - All plausible artificial radioactive sources entering the near-Earth space (NES)
      were systematized and consequences of various large radiation accidents and
      catastrophes to Earth and NES were analyzed. Aggressive "population" of near
      Earth orbits by space stations with rotating crews, unmanned research platforms
      and observatories extends "borderlines" of the noosphere raising at the same time
      concerns about the noosphere radiation safety and global radioecology.
      Specifically, consideration is given to the facts of negative effects of space
      power reactor facilities on results of orbital astrophysical investigations.

PMID- 15500165
TI  - [Formalized evaluation of the ionizing radiation effects modification due to the
      contribution of a number of factors on Earth and in space flight].
AB  - The article reviews data of radiobiological investigations into the contribution
      of different physical factors preceding and succeeding exposure to the lethal
      doses of radiation. To reveal synergism, results of the experiments flown on
      biosats Kosmos-690 with and Kosmos-605 without a gamma-source were compared and
      coefficients of modification of the immediate body response by specific
      spaceflight factors were determined. Expressed in dose equivalents, these
      modification coefficients are used to calculate the generalized dose and
      radiation risk to spacecrew in orbit. The earlier published radiation damage
      model served as a basis for a hypothesis explaining some of the effects of
      radiation combined with non-radiation factors in space flight.

PMID- 15500166
TI  - [Radiation safety of exploitation of radiation sources at the civil aviation
      airlines].
AB  - Radiation risks from isotope-containing equipment, and ionizing and unused X-ray
      radiation sources are characterized and relevant normative documents with safety
      requirements to radiation sources installation, radiation safety of aircraft
      servicing and repair, hand luggage control and heavy luggage registration,
      personal protection items, system of radiation monitoring at airlines and
      aircraft works, and liability for breach of performance guidelines are cited.

PMID- 15500167
TI  - [Socio-psychological and ecological aspects within the system of nuclear
      radiation risk mitigation].
AB  - The authors bring into light several aspects of nuclear radiation risks, i.e.
      physical safety of nuclear technologies and ecology, place of operator within the
      nuclear radiation safety system (proficiency, protective culture, safety guides)
      and consider approaches to the human factor quantification within the system of
      mitigation of risks from nuclear technologies, and IAEA recommendations on
      probable risk estimation. Future investigations should be aimed at extension of
      the radiation sensitivity threshold, personnel selection as by psychological so
      genetic testing for immunity to ionizing radiation, development of pharmachemical
      and physical protectors and methods of enhancing nonspecific resistance to
      extreme, including radiation, environments, and building of radiation event
      simulators for training.

PMID- 15500168
TI  - [Evaluation of the radiation risk of determinate effects from space radiation in
      a piloted mission to Mars].
AB  - Solar cosmic rays (SCR) are one of the sources of radiation risk specific to
      space flights. On Earth, occupational exposure has a regular character and
      radiation risk is an attribute of nothing else but stochasticity of
      radiobiological effects. In space flight, SCR impart stochasticity to the
      radiation environment and, therefore, probability to all, including determinate,
      radiobiological effects. The most dangerous effect is radiation disease the
      dosimetric functional of which is an equivalent dose to the blood-forming organs.
      In addition, this radiation pathology is modulated by reparative processes in the
      blood-forming tissue which must be also taken into account during radiation risk
      evaluation. Using the speculated mission to Mars as an example, it was shown that
      radiation risk of determinate effects defined as probability of death by
      radiation disease in consequence of exposure to SCR can be comparable in value to
      the risk from stochastic effects.

PMID- 15500169
TI  - [Effects of low-dose accelerated charged particles of varying LET on cytogenetic
      changes in comeal epithelium cells in mice].
AB  - Effects of low-dose heavy charged particles (HCP) of varying LET on quantitative
      and qualitative changes in chromosomes of the comeal epithelium cells were
      studied in mice. Cytogenetic damages in the comeal epithelium cells were analyzed
      after irradiation by ions of helium and carbon with an energy of 300 MeV/nucleon
      (LET = 1.36 and 12.6 keV/microm), and 137Cs gamma-rays with the doses from 5 to
      200 Gy. Accelerated nuclei were shown to be more effective. On the basis of
      aberrant mitosis rate, RBE values for helium and carbon ions in 24, 72 and 120
      hrs. after irradiation were 6.0; 3.6 and 2.2 for helium ions and 7.0; 3.8 and 2.4
      for carbon ions, respectively. The dose region of 20-30 Gy turned to be dose
      independent. It was established that the period of chromosomal aberration
      sustenance in cells is also LET-dependent.

PMID- 15500170
TI  - [Informational technologies in medical support to an interplanetary mission
      crew].
AB  - Plans to send humans to Mars dictate revision of the whole crew medical support
      system. Autonomy of the mission will extend crew responsibilities for all
      dimensions of medical support. The article compares and contrasts medical support
      of crews on orbital and interplanetary missions, and considers the place and
      functionality of medical informational technologies in a mission to Mars.

PMID- 15500171
TI  - [New criteria for prediction of individual endurance of physical stress].
AB  - A team of eight triathlon athletes was tested for endurance to extreme physical
      stress during training session. Two new functional parameters were analyzed, i.e.
      the cell membrane beta-adrenoreactivity (beta-ARM) and activity of leukocyte
      tyrosine hydroxilase (TH) as a key enzyme of the dophaminergic system. In four
      athletes who had been included in the national team at a later date beta-ARM and
      Kth values were 2-3-fold beyond the physiological norm, whereas in the other four
      (reserves) the parameters were below the upper limits. These data suggest that
      abnormal beta-ARM and Kth values can be treated as biochemical prognostic
      criteria for endurance of extreme phyical stress.

PMID- 15500172
TI  - [Carbon dioxide SHF-desorption from liquid regenerated sorbent in a
      physicochemical human life support system].
AB  - Desorption of carbon dioxide from monoethanol ethylene diamine solution with the
      use of SHF was compared to the thermal technology both in static condition and
      with a fixed absorbent expenditure. In the static condition, CO2 evacuation by
      SHF was more complete, without precipitation, and within a short interaction
      time. With absorbent expenditure and CO2 production rate permanent, SHF
      desorption occurred at a lower temperature and, therefore, lower absorbed power
      than the conventional thermal process. Testing demonstrated efficiency of the non
      inertial volumetric SHF heating in regeneration of the liquid absorbent charged
      in physicochemical life support systems for different pressurized habitats.

PMID- 15500173
TI  - [Neoplastic transformation of mouse fibroblasts under the influence of high
      energy protons and gamma-rays].
AB  - Oncoginic transformations of mouse fibroblasts C3H10T1/2 after exposure to proton
      energies 150 and 584 MeV were compared with fibroblast effects of gamma
      radiation. Prior to exposure, cell populations (2.7 x 10(3) cells/cm2) were
      inoculated in plastic vials with the surface area of 75 cm2 and cultivated 11
      days. Survivability was determined by comparing the number of cell colonies in
      irradiated and non-irradiated (control) vials. Transformation rate was calculated
      by dividing the total transformation focus number by the number of survived cells
      in a vial. Rate of oncogenic transformations after gamma- and proton (584 MeV)
      irradiation was essentially identical, i.e. the parameter grew rapidly at the
      doses < 1 Gy and slowed down at the doses > 1 Gy. In the dose interval between 1
      and 5 Gy, transformation rate for proton energy 150 MeV was found low compared
      with gamma-radiation and proton energy 584 MeV. It is hypothesized that the
      different transformation rate after exposure to proton energy 150 MeV is linked
      with the high linear energy transfer as compared with the proton energy of 584
      MeV and gamma-radiation.

PMID- 15500174
TI  - Nursing's voice--a vital force on election day.

PMID- 15500176
TI  - OSHA's worrisome regulations hurt nurses.

PMID- 15500179
TI  - Chronic obstructive pulmonary disease: epidemiology, pathogenesis, disease
      course, and prognosis.
AB  - Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death
      in the United States and is increasing in incidence. COPD is easily identified in
      its early stages by spirometry, yet it is still underdiagnosed, largely because
      this simple test is not being done in patients at risk for the development of
      COPD. The most important risk factor by far is cigarette smoking-smoking
      cessation or even a decrease in smoking can substantially reduce the risk for the
      development and/or rate of progression of COPD. Increased public awareness, early
      diagnosis and intervention, and secondary prevention by primary care providers
      may help reverse the trend of escalating prevalence, mortality, and premature
      morbidity associated with COPD.

PMID- 15500180
TI  - Long-term pharmacologic management of patients with chronic obstructive pulmonary
      disease.
AB  - Various pharmacologic agents are available for the long-term maintenance
      management of chronic obstructive pulmonary disease (COPD). The efficacy of these
      agents is based on their ability to decrease COPD symptoms, improve pulmonary
      function and quality of life, and reduce the frequency of acute exacerbations.
      Bronchodilators form the foundation of COPD therapy. Anticholinergic
      bronchodilators, such as ipratropium bromide and especially tiotropium, are first
      line anticholinergic agents that can be used alone or in combination with long
      acting or short-acting beta2-agonists to achieve these primary goals of COPD
      treatment. Methylxanthines are useful primarily for their nonbronchodilatory (ie,
      positive) effects on pulmonary arterial pressure, pulmonary vascular resistance,
      renal blood flow, and glomerular filtration rate. Inhaled corticosteroids are
      reserved only for the few patients with severe disease who experience symptoms
      and acute exacerbations despite optimized multiple bronchodilator therapy. This
      article reviews agents that are currently available and those that are in
      development for the long-term management of COPD, with special emphasis on the
      anticholinergic bronchodilators.

PMID- 15500181
TI  - Long-term nonpharmacologic management of patients with chronic obstructive
      pulmonary disease.
AB  - A comprehensive treatment plan for managing patients with chronic obstructive
      pulmonary disease (COPD) involves appropriate use of nonpharmacologic as well as
      pharmacologic interventions. Nonpharmacologic intervention begins with an
      aggressive effort toward smoking cessation, which has been proven to slow the
      accelerated rate lung function that characterizes COPD and to decrease all-cause
      mortality in patients with COPD. Proper nutrition and regular exercise are vital
      for all patients. Some patients with documented hypoxemia from more severe
      disease may require long-term oxygen therapy. Pulmonary rehabilitation benefits
      most patients, and even surgical intervention with lung volume reduction surgery
      or lung transplantation may help a limited number of patients. This article
      reviews the nonpharmacologic interventions that may be used in conjunction with
      maximized pharmacologic therapy in the long-term management of patients with
      COPD.

PMID- 15500182
TI  - A histomorphometric study of osteocytic lacunae in interradicular bone with
      periodontal disease.
AB  - Previous studies report on the differences in volume of osteocytic lacunae that
      are associated to different local and systemic bone pathologies. Alterations have
      also been reported in rats with periodontal disease. The aim of the present study
      was to assess the histomorphometric pattern of osteocytic lacunae of the
      interradicular septum in human molars with periodontal disease (PD). We took
      samples of the interradicular septum of 31 molars with indication of extraction
      of male and female patients, 18-55 years old, who attend the Department of
      Surgery II of the Faculty of Dentistry, National University of Cordoba and
      private centers. Clinical records were prepared for each patient. The
      corresponding radiographs were taken for all the patients. We studied 11 samples
      of molars with slight PD and 12 control molars free from PD. Ten samples of
      healthy bone corticals of vestibular or lingual tables obtained from
      histopathology archives were also assessed. Following extraction with atraumatic
      pincers, the interradicular septum was removed. The samples were fixed in
      buffered formaline, decalcified in EDTA and embedded in paraffin. Ten micrometer
      sections were stained with H&E and Masson's trichromic technique. The sections
      were analyzed by light microscopy. A minimum of 50 lacunae were selected at
      random in each sample for histomorphometric evaluation. Semi-automatic evaluation
      of the area and diameters of the lacunae was performed employing an image
      analyzer and the PRO IMAGE PLUS software. The data showed that the volume of
      osteocytic lacunae of interradicular bone is larger than that of the cortical
      bone of the vestibular or lingual tables. The latter are more ribbon-shaped and
      their minor diameter is smaller. No differences were found between the osteocytic
      lacunae of the interradicular bone of healthy molars and that of molars with
      slight periodontal disease. Given that the experimental data evidenced volume
      changes in osteocytic lacunae of severe, inflammatory periodontal lesions, it
      would be interesting to examine the volume changes in osteocytic lacunae in
      patients with varying degrees of periodontal disease to examine the role of
      osteocytes in the development and progression of periodontal disease.

PMID- 15500183
TI  - Low and high molecular weight chitosans interactions with Streptococcus mutans:
      an in vitro study.
AB  - We evaluated the in vitro capacity of high and low molecular weight chitosans
      (HMWCh and LMWCh) to inhibit the adherence of strains of S. mutans obtained from
      the American Type Culture Collection (ATCC,25175) to artificial saliva-coated
      hydroxiapatite beads. The effect of these biopolymers was assessed in terms of
      pH, ionic force, minimum inhibitory concentration (MIC) and antibacterial
      activity. The results show that HMWCh is modified by a rise in pH (7.0) and ionic
      strength. The induced conformational changes lead to the formation of rigid
      meshes capable of aggregating and entrapping S. mutans. This process is
      associated to the properties of HMWCh. LMWCh gave rise to smaller aggregates that
      exhibited a comparatively reduced interaction capacity. The MIC for HMWCh was 0.5
      g% and evidenced the bacteriostatic action of the aggregates. We conclude that
      HMWCh would exert an inhibitory effect on the process of specific adsorption of
      S. mutans to saliva-coated hydroxiapatite beads.

PMID- 15500184
TI  - Knowledge, behavior, and attitudes of adolescent university students towards HIV
      infection and AIDS.
AB  - The aim of this study was to evaluate the knowledge, behavior, and attitudes of
      students entering the University of Buenos Aires (UBA) towards HIV/AIDS, as well
      as to determine the differences between genders and between groups with different
      behavior in terms of HIV/AIDS risk behavior, through the conduct of an ad hoc
      semi-structured questionnaire. This questionnaire was completed anonymously by
      12,000 university students going in for compulsory medical check-up at the Health
      and Social Welfare Office of the UBA. Two thousand cases were selected by simple
      randomized sampling and statistically analyzed. Results revealed that: (1) 87.2%
      of the population under study was between 18 and 27 years old; (2) the students'
      knowledge of the subject was acceptable; (3) the percentage of respondents who
      reported having sexual intercourse with more than one person decreased as the
      number of sexual partners in a year increased. Less than 1.5% explicitly stated
      being homosexual or bisexual; (4) 53.9% of the men and 46.7% of the women claimed
      they always used condoms; (5) analysis of the perception of their own risk showed
      that 75% considered they were not at risk; (6) between 95.8% and 98% were in
      favor of developing educational-preventive activities and 64.2% thought
      compulsory AIDS screening for job applicants or candidates for educational
      courses was discrimination. CONCLUSIONS: (a) Information available to admission
      course students is sufficient. However, there are contradictions in their
      responses about their own behaviors; (b) Most of the respondents are in favor of
      the corresponding Faculties implementing educational and preventive measures. The
      students would regard the University's intervention as a way of fulfilling its
      social role.

PMID- 15500185
TI  - A quantitative method to evaluate corrosion products in tissues.
AB  - The use of odontological or orthopedic metal implants requires the availability
      of techniques to estimate tissue response to the corrosion processes. In previous
      experimental studies we showed the deposition of corrosion products not only
      locally (Olmedo et al., Implant Dent 2003; 12: 75-80) but also systemically
      (Olmedo et al., J Mater Sci: Mater in Medic 2002; 13: 793-796) in organs such as
      liver, spleen and lung. The aim of the present study was to propose a method to
      quantitatively assess the tissue deposits of the corrosion products of the
      materials used to manufacture implants. The samples (liver and lung) were
      embedded in paraffin, and the histological sections were submitted to thickness
      standardization. The quantitative evaluation of the deposits was performed in an
      MPM-800 (Carl Zeiss)* microscope. The light microscopy images were digitalized
      and then analyzed employing the DNA-IBAS-Kontron software that allows for the
      identification and evaluation of cells loaded with corrosion products (objective
      20x). The following end-points were assessed: total field area, number of
      deposits of corrosion products, partial and total area of the deposits, and the
      ratio between volume of the deposits and tissue volume. The method proposed
      serves to quantitatively evaluate, at light microscopy level, the deposition of
      corrosion products in tissues.

PMID- 15500186
TI  - Analysis of intrinsic pH, soluble solids and buffer effect of non-alcoholic
      drinks.
AB  - The aim of the present study was to determine in vitro the erosive capacity of
      different common drinks employing intrinsic pH, soluble solids and buffer effect
      at pH 5.5 and pH 7.0 as end-points. Fifty- two drinks of mass consumption were
      selected and grouped according to type into 3 groups: 1: Juices (n = 23); 2: soy
      beverages (n = 18); 3: carbonated drinks (n = 11). The mean and standard
      deviation were calculated for each drink and for each group of drinks. The
      statistical analysis of the data was performed by Analysis of Variance (ANOVA)
      and Tukey's test for multiple comparisons. Statistical significance was set at p
      < or = 0.05. The data showed that the 3 groups exhibited initial acid pH values.
      Natural juices had the greatest buffer effect. The soluble solids, expressed as
      Brix Grades, showed statistically significant differences between the regular and
      light forms of carbonated and soy beverages. The light and regular forms of the
      drinks included in the study failed to show statistically significant differences
      at pH 5.5 and pH 7.0.

PMID- 15500187
TI  - Your chance to do the right thing.

PMID- 15500188
TI  - The case of the missing evidence: antidepressant use in children.

PMID- 15500189
TI  - Don't overlook childhood depression.
AB  - Although depression is not uncommon among American children, clinicians often
      miss it. Because depression is associated with somatic complaints, social
      impairment, and suicide, health care providers must know the risk factors for
      depression and be able to recognize the symptoms and implement an effective
      treatment plan.

PMID- 15500190
TI  - Dry skin: common causes, effective treatments.

PMID- 15500191
TI  - Multiple myeloma.

PMID- 15500192
TI  - Are cardioselective beta-blockers safe to use perioperatively in patients with
      COPD?

PMID- 15500193
TI  - Diversify the PA profession: a call to action.

PMID- 15500194
TI  - Case of the the month. Nephrolithiasis.

PMID- 15500195
TI  - Synthesis and calcium channel antagonist activity of new 1,4-dihydropyridine
      derivatives containing lipophilic 4-imidazolyl substituents.
AB  - A group of cycloalkyl and aryl ester analogues of nifedipine (CAS 21829-25-4), in
      which the ortho-nitrophenyl group at position 4 is replaced by a 2-phenyl-4(5)
      imidazolyl substituent, were synthesized and evaluated as calcium channel
      antagonist using the high K+ contraction of guinea-pig ileal smooth muscle. The
      results for the symmetrical esters in cycloalkyl and aryl esters showed that
      increasing the length of the methylene chain in C3 and C5 ester substituents
      (from n = 0 to n = 3) increased activity. A comparison of the effect of
      cyclohexyl relative to phenyl substituent showed that cyclohexyl derivatives were
      more active than phenyl derivatives. In contrast to symmetrical derivatives,
      comparison of the activities of asymmetrical esters showed that phenyl
      derivatives were more active than cycloalkyl derivatives. The results demonstrate
      that compounds 5a, 8a, 8l and 8n had similar activity to and compounds 5b, 5c, 5d
      and 5i were more active than the reference drug nifedipine. The structure
      activity data indicate that the 4-(2-phenyl-4(5)-imidazolyl) moiety is a
      bioisoester of the o-nitro group of nifedipine.

PMID- 15500196
TI  - Antioxidative effects of benidipine hydrochloride in patients with hypertension
      independent of antihypertensive effects. Relationship between blood pressure and
      oxidative stress.
AB  - This study investigated the significance of measuring plasma level of
      thiobarbituric acid reactive substance (TBARS) in patients with hypertension and
      compared the clinical effects of benidipine hydrochloride (CAS 91599-74-5,
      Coniel) and amlodipine besylate (CAS 111470-99-6) on plasma TBARS. At first,
      blood pressure and plasma TBARS were measured in 85 untreated patients (48 males
      and 37 females, 68 years old on average) with at least one risk factor of
      cardiovascular disease to investigate factors which had influence on plasma
      TBARS. As the result, plasma TBARS was significantly higher in those with
      hypertension, which was also true when adjusted for other factors (r = 0.359, p<
      0.01). Among these patients, benidipine hydrochloride at the dose of 4 mg/day was
      administered to 49 patients with hypertension or angina pectoris. All patients
      stratified for each factor showed significantly decreased plasma TBARS after
      benidipine hydrochloride treatment. Second, 40 untreated patients with essential
      hypertension were randomly assigned to the amlodipine group (5-7.5 mg/day) or
      benidipine group (4-8 mg/day) to compare the plasma TBARS levels. Plasma TBARS
      levels were significantly decreased in both groups. The amlodipine group showed a
      positive correlation between the decrease in plasma TBARS level and those in both
      diastolic and systolic blood pressures after treatment. On the other hand,
      benidipine hydrochloride decreased plasma TBARS to a greater degree than both
      diastolic and systolic blood pressures. These findings suggest that patients with
      hypertension have high plasma TBARS, and benidipine hydrochloride decreases not
      only blood pressure but also oxidative stress in the clinical practice.

PMID- 15500197
TI  - Clinical, double-blind, placebo-controlled study investigating the combination of
      acetylsalicylic acid and pseudoephedrine for the symptomatic treatment of nasal
      congestion associated with common cold.
AB  - It was the aim of this clinical study to demonstrate the efficacy of 1000 mg
      acetylsalicylic acid (ASA, CAS 50-78-2) in combination with 60 mg pseudoephedrine
      (PSE, CAS 90-82-4), compared with placebo, in the symptomatic treatment of nasal
      congestion associated with the common cold. A further aim was to demonstrate the
      efficacy of 500 mg ASA + 30 mg PSE and of 1000 mg paracetamol (CAS 103-90-2) + 60
      mg PSE (active control) in the symptomatic treatment of nasal congestion. The
      study was designed as a randomized, two-center, double-blind, double-dummy,
      placebo-controlled, parallel-group, single-dose efficacy and safety trial over 6
      h and was carried out in the USA. In total, at two centers, 643 patients who had
      a history and diagnosis of acute upper respiratory tract infection (URTI), were
      included; they showed symptoms such as nasal congestion, scratchy/sore throat,
      headache, generalized muscle ache, earache, runny nose, fever, sneezing etc. The
      investigational drugs ASA and PSE were both provided as granules in sachets and
      the granules were dissolved in water before administration; the combined
      preparation of paracetamol + PSE was administered as commercially available
      tablets encapsulated for blinding. For all preparations, matching placebos were
      provided. The primary efficacy variable was the area under the curve for
      differences from baseline on a nasal congestion scale in the first 2 h after
      treatment. To be eligible for the study, otherwise healthy volunteers were to
      present with nasal stuffiness of recent onset that reached a score of at least 6
      on the 11-point scale for nasal congestion (0 = not stuffy, 10 = very stuffy).
      The primary analysis of the primary efficacy variable was calculated by analysis
      of variance including treatment group, severity (moderate/severe) and center as
      main strata. The analysis was performed using the intent-to-treat population. All
      active treatments proved to be statistically significantly superior to placebo
      with regard to the primary efficacy variable. Significant superiority of active
      treatment compared with placebo could also be demonstrated for an interval of up
      to 6 h after intake of the drug and for the relief of nasal congestion. The lower
      dose did not reveal significant different results compared with placebo for
      relief of nasal congestion in patients with a severe nasal congestion score at
      baseline. As well in patients with moderate nasal congestion score (NCS) at start
      of the study the difference from baseline in the NCS compared with placebo was
      not statistically significant. Thus a trend towards better efficacy in the higher
      dose could be assumed. No difference was found between 1000 mg ASA + 60 mg PSE
      and the active control. There were no differences between the two centers. The
      treatment proved to be safe and well tolerated, without relevant differences
      between the four treatment groups. Main adverse events were found to be related
      to the upper respiratory tract infection or were of gastrointestinal nature. In
      conclusion, the combination of ASA with PSE can be considered as an effective and
      safe remedial for the symptomatic treatment of the nasal congestion during URTI.

PMID- 15500198
TI  - [Comparative in vitro and in vivo studies on the permeation and penetration of
      ketoprofen and ibuprofen in human skin].
AB  - The aim of the present in vitro and in vivo studies was to compare the permeation
      and penetration of a 2.5% ketoprofen (CAS 22071-15-4) gel [Phardol Schmerz-Gel
      (Test-D)] with the permeation and penetration of two other ketoprofen gels (Ref
      I, Ref-E) and an ibuprofen (CAS 15687-27-1) gel (Ref-D) on excised human skin.
      Furthermore, in vivo studies were performed. The permeation studies utilizing
      static Franz diffusion cells allow the determination of the transdermal
      (systemic) transport, whereas the penetration studies in vitro (according to the
      Saarbrucker model) and in vivo permit setting up a concentration-depth profile.
      For this purpose the permeation kinetics of ketoprofen from three different gels
      (each containing 2.5% ketoprofen) over a period of two days were determined at
      heat-separated human skin of different donors. The in vitro permeability
      coefficients for Test-D (6.50 x 10(-7) cm x s(-1)) and Ref-I (5.72 x 10(-7) cm x
      s(-1)) were comparable and the transport occurred for both by a factor of 8-9
      faster than with Ref-E (0.78 x 10(-7) cm x s(-1)). In parallel to the permeation
      studies with ketoprofen, the permeability coefficient of caffeine from an
      ointment was assessed using the skin biopsies of the same donors as a quality
      assurance. In a second part of the studies, the in vitro penetration of
      ketoprofen from Test-D was determined over a period of 3 h at three different
      skin biopsies in comparison to a commercially available 5% ibuprofen gel (Ref-D).
      As a main result a concentration-depth profile for ketoprofen and ibuprofen could
      be issued. The ketoprofen (37.7 +/- 12.1 microg/cm2) and the ibuprofen (30.1 +/-
      6.0 microg/cm2) penetrate to the same order of magnitude into the upper part of
      the Stratum corneum, whereas ibuprofen stronger accumulates in the deeper layers
      (ketoprofen: 27.3 +/- 8.5 microg/cm2; ibuprofen: 73.7 +/- 31.1 microg/cm2). An
      additional in vivo penetration study was performed with Test-D to set up an in
      vitro-in vivo (IVIV) correlation. Over a period of 3 h, the amount of ketoprofen
      in the Stratum corneum in vivo was 78.4 +/- 19.1 microg/cm2 being comparable to
      the in vitro data.

PMID- 15500199
TI  - Thiazolyl and isothiazolyl azomethine derivatives with anti-inflammatory and
      antioxidant activities.
AB  - Several thiazolyl/benzothiazolyl/benzo[d]isothiazolyl Schiff bases and hydrazones
      have been tested as anti-inflammatory agents and five new compounds have been
      synthesized. The anti-inflammatory activity was examined in vivo using the
      carrageenin induced mice paw edema test (inhibition 16.3-64%). The compounds were
      tested for antioxidant activity as hydroxyl scavengers and for their ability to
      interact with the stable free radical 1,1-diphenyl-2-picryl-hydrazyl (DPPH). Both
      anti-inflammatory and antioxidant activities depended on some structural
      characteristics of the synthesized compounds.

PMID- 15500200
TI  - Effects of a new maintenance fluid containing sodium acetate as the base
      component and electrolytes during renal biopsies in patients with chronic
      glomerulonephritis.
AB  - A new maintenance fluid containing sodium acetate as the base component and
      electrolytes (Veen 3G, test preparation) for a maximum of 24 h was infused to 15
      patients hospitalized for renal biopsies and requiring intravenous supplements of
      water, electrolytes and energy because oral or enteric ingestion was inadequate
      or impossible. A physical examination, blood chemistry tests and urinalysis were
      performed, and the global improvement rating was obtained by scoring the effects
      on a) maintenance of cardiovascular hemodynamics (systolic blood pressure), b)
      blood glucose control (blood glucose level), c) utilization of sugar (free fatty
      acids, total ketone bodies), d) maintenance of serum electrolytes, e) amount of
      sugar excreted in the urine and f) maintenance of urinary volume. The results
      were excellent or good in all of the 15 patients analyzed. The test agent was not
      the direct cause of any adverse events or abnormal changes in laboratory
      findings, and no safety-related problems were observed in any of the patients.
      These results indicated that the test preparation used in this study is a
      clinically useful and highly safe fluid agent.

PMID- 15500201
TI  - Immunostimulatory effect of coumarin derivatives before and after infection of
      mice with the parasite Schistosoma mansoni.
AB  - Coumarins (pyranobenzopyran derivatives) (coumarin: CAS 91-64-5), organic
      compounds of known chemotherapeutic importance against bacteria, infectious
      diseases and tumors, were tested for their immunomodulatory effects. The
      compounds used in the present study were 1H,9H-3-amino-7-methyl-9-oxo-1
      phenylpyran(2,3-h)(1)benzopyran-2-carbonitrile; 1H,9H-2-carboxamido-7-methyl-3,9
      dioxo-1-phenylpyran(2,3-h)(1)benzopyran; 4H,8H-2-amino-7-bromo-6-methyl-10-nitro
      8-oxo-4-(p-nitrophenyl)-pyran(3,2-g)(1)benzopyran-3-carbonitrile; 4H-7-bromo-3
      carboxamido-2,8-dioxo-6-methyl-10-nitro-4-(p-nitrophenyl)2,8
      dihydropyran(3,2g)(1) benzopyran. Mice were injected subcutaneously (0.75
      mg/mouse) with each of the compounds for three successive days, then each animal
      was exposed to 100 Schistosoma mansoni cercariae. The effect on the humoral
      immune response was detected by measuring immunoglbulin G (IgG) levels using
      enzyme-linked immunosorbent assay (ELISA) against E. coli lysate, soluble worm
      antigen preparation (SWAP) and cancer bladder tissue homogenates. The reactivity
      of IgG to E. coli lysate was measured in sera of treated mice before and after
      infection. However, for SWAP and cancer tissue homogenates the IgG was measured
      only after infection. Mice given compounds 2, 3 and 4 showed a concentration
      dependent increase in IgG level against E. coli lysate as compared to untreated
      uninfected mice. Animals given compounds 3 and 4 followed by S. mansoni infection
      showed a significant increase (p< 0.05) in IgG level against the same antigen.
      Moreover, compounds 1, 2 and 4 significantly (p < 0.05) stimulated IgG production
      when measured against SWAP. Compounds 2, 3 and 4 induced a significant (p < 0.05)
      IgG response to cancer bladder tissue homogenates as compared to infected control
      mice. At the cellular level, treatment with compounds 1, 2, 3 and 4 caused a
      significant increase (p < 0.05) in the mean percentage of CD4+-T cells as
      compared with normal control, whereas, compounds 1, 2 and 3 stimulated a
      significant increase (p < 0.05) in the mean percentage of CD8+-T cells. Six weeks
      post-infection compounds 3 and 4 induced a significant stimulation (p< 0.05) in
      the mean number of both CD4+ and CD8+-T cells. The study showed that the
      compounds used have an immunomodulatory effect at both humoral and cellular
      levels.

PMID- 15500202
TI  - Synthesis and cytotoxic studies of hydroximino derivatives of some 16E
      arylidenosteroids.
AB  - Oxime and dioxime derivatives of various 16E-arylidenosteroids in the androstene
      series have been prepared and evaluated at the National Cancer Institute (NCI),
      Bethesda (USA) for their antineoplastic activity against various tumor cell lines
      in order to determine the structural requirements for cytotoxic activity. Aldol
      condensation of dehydroepiandrosterone (DHA) and DHA acetate with various
      aldehydes followed by treatment with hydroxylamine hydrochloride resulted in the
      formation of 16E-arylidenosteroid-oxime system. Oximes 15, 16 and compound 20
      with a higher degree of oxidation in ring A have been found active in a 60 cell
      line antitumor prescreen by virtue of their cytotoxic effect against one or more
      tumor cell line and were further referred for in vivo hollow fiber bioassay.
      These compounds showed interesting intraperitoneal and subcutaneous scores in the
      in vivo hollow fiber bioassay and have been referred to the Biological Evaluation
      Committee for Cancer Drugs for further detailed in vivo testing.

PMID- 15500203
TI  - A new method using flow cytometry to measure the effects of drugs on gastric
      emptying and gastrointestinal transit in mice.
AB  - The use of radiolabelled markers is considered to be a gold standard for
      assessing gastric emptying and gastrointestinal transit in mice and rats, but
      their use has increasingly been restricted due to health concern. Therefore, a
      new method using fluorescent polystyrene microbeads and flow cytometry was
      devised. Saline containing fluorescent markers (together with non-fluorescent
      microbeads) was infused into the stomach of each mouse and gastric emptying and
      gastrointestinal transit were calculated by measuring the quantity of the
      fluorescent microbeads in the gastrointestinal tract using flow cytometer. The
      effects of saline (as a control), morphine (CAS 52-26-6) and dexmedetomidine (CAS
      113775-47-6) were tested. Both gastric emptying and gastrointestinal transit
      measured with this method (after i.p. injection of saline) were similar to those
      reported previously using the conventional radiolabelled methods. Morphine
      significantly inhibited both gastric emptying and gastrointestinal transit in a
      dose-dependent manner. Dexmedetomidine did not significantly inhibit gastric
      emptying but inhibited gastrointestinal transit. These results were also similar
      to those obtained using the conventional radiolabelled method. The method using
      fluorescent microbeads and flow cytometry may be a reliable alternative to the
      methods using radioisotope for studying the effects of drugs on gastric emptying
      and gastrointestinal transit.

PMID- 15500205
TI  - Loss of care home capacity 'is a tragedy' for older people.

PMID- 15500204
TI  - Positive view beats off negative effects.

PMID- 15500206
TI  - Room for improvement.

PMID- 15500207
TI  - Down with discrimination.

PMID- 15500208
TI  - Generation game.

PMID- 15500209
TI  - Multi-disciplinary person-centred care: has government policy helped or hindered?

PMID- 15500211
TI  - Music therapy: striking a chord with care home residents.

PMID- 15500210
TI  - Reducing deaths from stroke: a focused review of the literature.

PMID- 15500212
TI  - The evidence base for gerontological nursing practice. Part 2: Making sense of
      the evidence.
AB  - This is the second of two articles exploring the meaning of 'evidence-based
      practice'. The first, in last month's issue, considered what is meant by
      'evidence'. This month, Jan Draper examines how literature reviews can help
      nurses make sense of the variety of evidence available to them.

PMID- 15500213
TI  - Anticoagulants.

PMID- 15500214
TI  - Mental health in acute care.

PMID- 15500215
TI  - Care homes consumer research.

PMID- 15500216
TI  - Supporting choice.

PMID- 15500217
TI  - The Pennine way.

PMID- 15500218
TI  - Scaling the heights.

PMID- 15500221
TI  - 'Gonnae no dae that'.

PMID- 15500222
TI  - Why we love our nurses.

PMID- 15500223
TI  - A champion for race equality and diversity. Interview by Lucy Gooding.

PMID- 15500224
TI  - Facing danger.

PMID- 15500225
TI  - Formula for happy nurses.

PMID- 15500226
TI  - Avoiding rebellion.

PMID- 15500227
TI  - Monitoring sharps injuries: EPINet surveillance results.
AB  - Sharps injuries are one of the main types of accident sustained by NHS staff. The
      RCN's Be Sharp Be Safe campaign was launched in 2001 with the aim of reducing
      sharps injuries and includes a surveillance project to describe the current
      pattern of sharps injuries being experienced in participating trusts. This
      article gives an overview of the results from the second year of the surveillance
      project and indicates how the data can be used to help improve practice. Nurses
      emerge as the staff group reporting the highest proportion of injuries recorded
      in the study period. The most common sharps injury scenario involves nurses
      giving injections in the patient's room or ward area. Aspects of poor disposal
      practice and incidents involving the recapping of needles continue to result in
      injuries and are worthy of further investigation. Analysis of the data by
      location can highlight specific tasks which could be reviewed to identify safer
      working practices.

PMID- 15500228
TI  - Improving perinatal mental health care.
AB  - Pregnancy and the puerperium can bring many emotional, physical and social
      changes to the mother, her partner and the rest of the family. While many mothers
      find these changes--such as the experience of pregnancy or the addition of a new
      member to the family--joyous, some do not share these positive feelings and often
      undergo emotional upheaval resulting in severe biopsychosocial distress. This
      period of distress does not only subject the mother and her family to increased
      risk of psychological crisis, mental illness and developmental disturbances, but
      may also, if untreated, result in the fatalistic outcomes of infanticide or
      suicide. In this article, the author calls for a more robust, co-ordinated and
      interdisciplinary approach to perinatal mental health services.

PMID- 15500230
TI  - Politicians serious about winning nursing's vote?

PMID- 15500229
TI  - Total hip replacement.
AB  - This article provides an overview of total hip replacement and the nurse's role
      in caring for patients undergoing this procedure.

PMID- 15500231
TI  - Shared experience.

PMID- 15500232
TI  - Is the profession prepared for nurse prescribing in hospitals?
AB  - Although originally developed for primary care, nurse prescribing is being
      extended to hospitals. A range of developments has made it increasingly relevant
      to hospital-based nurses, and it should enable them to provide more effective
      care. However, nurses must be aware of a number of professional issues to ensure
      prescribing is extended for the benefit of patients rather than other
      professionals, and that it promotes holistic patient care.

PMID- 15500233
TI  - What you need to know about acoustic neuroma.

PMID- 15500234
TI  - Venepuncture.

PMID- 15500235
TI  - How 'nil by mouth' instructions impact on patient behaviour.
AB  - Preoperative fasting is a necessary intervention to minimise the risk of
      regurgitation and inhalation of gastric contents while under anaesthesia. But,
      despite clear written instructions, a significant number of patients choose to
      fast for a longer than suggested period. It is recommended that to improve
      practice patients should be reassured that they can maintain their oral intake
      until being instructed to stop. They should also receive information about oral
      comfort during fasting and when they can begin to eat and drink after their
      procedure.

PMID- 15500236
TI  - Understanding the necessity of ensuring safe sharps disposal.

PMID- 15500237
TI  - Living with peripheral vascular disease: patients and their carers.
AB  - AIM: This study explores the life experiences of those with peripheral vascular
      disease (PVD) and their carers. SAMPLE: A sample of seven couples. METHOD: An
      ethnographic approach using taped interviews in participants' own homes. RESULTS:
      Acceptance and adaptation were the core concepts to emerge from the data. Pain
      was identified as being central to the experience of PVD, with impaired mobility,
      loss of independence, disease progress and professional support being closely
      interrelated. CONCLUSION: The themes highlighted the devastating nature of the
      experience of living with PVD. Those with PVD need to feel that the complexity of
      their experience is understood while carers need to feel their role is
      acknowledged. Health care professionals should develop their understanding of the
      experience of PVD for patients and their carers, and apply this knowledge to
      their practice.

PMID- 15500238
TI  - Care and counselling in cosmetic surgery.

PMID- 15500239
TI  - Options increase in mental health.

PMID- 15500240
TI  - The government has waged war on salt.

PMID- 15500241
TI  - [CME-ECG 1. Solution. Tachycardia].

PMID- 15500242
TI  - [Identification of tumor antigens: strategies and perspectives].
AB  - The identification of tumor antigens is crucial for the development of antigen
      specific immunotherapies in cancer. Ideal target antigens for immunotherapies
      have a tumor specific expresssion pattern. Antigen expresssion in solid tumors is
      typically heterogenous. Therefore an effective immunotherapy should target
      several antigens simultaneously (polyvalent vaccine). Here we discuss strategies
      how tumor antigens can be identified and further analyzed as potential target
      antigens for active immunotherapy (cancer vaccine).

PMID- 15500243
TI  - [New antibodies in cancer treatment].
AB  - Since the development of hybridoma technology in 1975 monoclonal antibodies with
      pre-defined specificity can be produced. Only twenty years later did it become
      possible to make therapeutic use of monoclonal antibodies in oncology. To this
      end it was necessary to attach the antigen-binding site of a mouse antibody onto
      the scaffold of a human antibody molecule. Such chimeric or "humanized"
      antibodies may be used in passive immunotherapy without eliciting an immune
      response. Rituximab and trastuzumab are such humanized antibodies. They are used
      today routinely in the treatment of malignant lymphoma and breast cancer,
      respectively. These antibodies are usually used in combination with conventional
      cytostatic anticancer drugs.

PMID- 15500244
TI  - [Medical decision making: some aspects].
AB  - Three main aspects of medical decision making will be shortly described in this
      article. Comprehensible information is required to make decisions. The question
      is, how much information is needed to make decisions, and a third aspect in this
      article concerns the decision maker. Research in the field of information
      transfer has shown that medical information, as presented in most journals, is
      difficult to understand. According to the classic decision theory, decisions are
      taken after collecting all available information. More recent research in
      decision making proves the hypothesis that human beings are able to decide
      correctly with much less information than presumed earlier. In medicine the
      patient is the decision maker, and the primary task of physicians is to inform
      the patient about his health status and enable him to reach a conclusion.

PMID- 15500245
TI  - [Chloral hydrate and diarrhea. A 76-year-old retired administration employee].

PMID- 15500246
TI  - [Low Pro-ANP levels in acute pulmonary embolism are possibly prognostic for a
      benign course].

PMID- 15500247
TI  - [Arctic vigor root].

PMID- 15500248
TI  - Estimation of the number of authentic orphan genes in bacterial genomes.
AB  - Genome annotation produces a considerable number of putative proteins lacking
      sequence similarity to known proteins. These are referred to as "orphans." The
      proportion of orphan genes varies among genomes, and is independent of genome
      size. In the present study, we show that the proportion of orphan genes roughly
      correlates with the isolation index of organisms (IIO), an indicator introduced
      in the present study, which represents the degree of isolation of a given genome
      as measured by sequence similarity. However, there are outlier genomes with
      respect to the linear correlation, consisting of those genomes that may contain
      excess amounts of orphan genes. Comparisons of genome sequences among closely
      related strains revealed that some of the annotated genes are not conserved,
      suggesting that they are ORFs occurring by chance. Exclusion of these non
      conserved ORFs within closely related genomes improved the correlation between
      the proportion of orphan genes and the IIO values. Assuming that the correlation
      holds in general, this relationship was used to estimate the number of
      "authentic" orphan genes in a genome. Using this definition of authentic orphan
      genes, the anomalies arising from over-assignments, e.g., the percentages of
      structural annotations, were corrected for 16 genomes, including those of five
      archaea.

PMID- 15500249
TI  - Identification and distribution of new insertion sequences in the genome of the
      extremely halotolerant and alkaliphilic Oceanobacillus iheyensis HTE831.
AB  - Six kinds of new insertion sequences (ISs), IS667 to IS672, a group II intron
      (Oi.Int), and an incomplete transposon (Tn852loi) were identified in the
      3,630,528-bp genome of the extremely halotolerant and alkaliphilic Oceanobacillus
      iheyensis HTE831. Of 19 ISs identified in the HTE831 genome, 7 were truncated,
      indicating the occurrence of internal rearrangement of the genome. All ISs except
      IS669 generated a 4- to 8-bp duplication of the target site sequence, and these
      ISs carried 23- to 28-bp inverted repeats (IRs). Sequence analysis revealed that
      four ISs (IS669, IS670, IS671, and IS672) were newly identified as belonging to
      separate IS families (IS200/IS605, IS30, IS5, and IS3, respectively). IS667 and
      IS668 were also characterized as new members of the ISL3 family. Tn8521oi, which
      belongs to the Tn3 family as a new member, generated a 5-bp duplication of the
      target site sequence and carried complete 38-bp IRs. Of the eight protein-coding
      sequences (CDSs) identified in Tn8521oi, three CDSs (OB481, OB482, and OB483)
      formed a ger gene cluster, and two other paralogous gene clusters were found in
      the HTE831 genome. Most of the ISs and the group II intron widely distributed
      throughout the genome were inserted in noncoding regions, while two ISs (IS667-08
      and IS668-02) and Oi.Int-04 were inserted in the coding regions.

PMID- 15500250
TI  - Complete chloroplast genome sequences from Korean ginseng (Panax schinseng Nees)
      and comparative analysis of sequence evolution among 17 vascular plants.
AB  - The nucleotide sequence of Korean ginseng (Panax schinseng Nees) chloroplast
      genome has been completed (AY582139). The circular double-stranded DNA, which
      consists of 156,318 bp, contains a pair of inverted repeat regions (IRa and IRb)
      with 26,071 bp each, which are separated by small and large single copy regions
      of 86,106 bp and 18,070 bp, respectively. The inverted repeat region is further
      extended into a large single copy region which includes the 5' parts of the rpsl9
      gene. Four short inversions associated with short palindromic sequences that form
      stem-loop structures were also observed in the chloroplast genome of P. schinseng
      compared to that of Nicotiana tabacum. The genome content and the relative
      positions of 114 genes (75 peptide-encoding genes, 30 tRNA genes, 4 rRNA genes,
      and 5 conserved open reading frames [ycfs]), however, are identical with the
      chloroplast DNA of N. tabacum. Sixteen genes contain one intron while two genes
      have two introns. Of these introns, only one (trnL-UAA) belongs to the self
      splicing group I; all remaining introns have the characteristics of six domains
      belonging to group II. Eighteen simple sequence repeats have been identified from
      the chloroplast genome of Korean ginseng. Several of these SSR loci show infra
      specific variations. A detailed comparison of 17 known completed chloroplast
      genomes from the vascular plants allowed the identification of evolutionary modes
      of coding segments and intron sequences, as well as the evaluation of the
      phylogenetic utilities of chloroplast genes. Furthermore, through the detailed
      comparisons of several chloroplast genomes, evolutionary hotspots predominated by
      the inversion end points, indel mutation events, and high frequencies of base
      substitutions were identified. Large-sized indels were often associated with
      direct repeats at the end of the sequences facilitating intra-molecular
      recombination.

PMID- 15500251
TI  - Large-scale analysis of gene expression profiles during early stages of root
      nodule formation in a model legume, Lotus japonicus.
AB  - Gene expression profiles during early stages of formation of symbiotic nitrogen
      fixing nodules in a model legume Lotus japonicus were analyzed by means of a cDNA
      array of 18,144 non-redundant expressed sequence tags (ESTs) isolated from L.
      japonicus. Expression of a total of 1,076 genes was significantly accelerated
      during the successive stages that represent infection of Mesorhizobium loti,
      nodule primordium initiation, nodule organogenesis, and the onset of nitrogen
      fixation. These include 32 nodulin and nodulinhomolog genes as well as a number
      of genes involved in the catabolism of photosynthates and assimilation of fixed
      nitrogen that were previously known to be abundantly expressed in root nodules of
      many legumes. We also identified a large number of novel nodule-specific or
      enhanced genes, which include genes involved in many cellular processes such as
      membrane transport, defense responses, phytohormone synthesis and responses,
      signal transduction, cell wall synthesis, and transcriptional regulation.
      Notably, our data indicate that the gene expression profile in early steps of
      Rhizobium-legume interactions is considerably different from that in subsequent
      stages of nodule development. A number of genes involved in the defense responses
      to pathogens and other stresses were induced abundantly in the infection process,
      but their expression was suppressed during subsequent nodule formation. The
      results provide a comprehensive data source for investigation of molecular
      mechanisms underlying nodulation and symbiotic nitrogen fixation.

PMID- 15500252
TI  - Single nucleotide polymorphisms in randomly selected genes among japonica rice
      (Oryza sativa L.) varieties identified by PCR-RF-SSCP.
AB  - DNA polymorphism of randomly selected genes in rice cultivars was analyzed by the
      polymerase chain reaction-restriction fragment-single strand conformation
      polymorphism (PCR-RF-SSCP) technique. Single DNA fragments were amplified from
      genomic DNA of the Nipponbare cultivar by 671 primer pairs among the 1000 primer
      pairs tested. PCR-RF-SSCP analysis using the 671 primer pairs detected
      polymorphism in 108 DNA fragments between 17 japonica paddy-rice cultivars. An
      average of 36.9 DNA fragments showed polymorphism between any pair of japonica
      paddy-rice cultivars. The nucleotide sequences of the polymorphic DNA fragments
      were determined for 50 alleles of 45 genes together with Nipponbare alleles. In
      these genes, 142 SNPs and 32 insertions/deletions were identified. Among these
      174 sequence variations, 71 were in exons, 78 in introns, and 25 in unassigned
      regions. There were 28 alleles which had sequence variations in the exons. One
      allele had a 1-bp deletion in the exon causing a frame-shift mutation, 15 alleles
      had missense mutations, and the other 12 alleles had synonymous changes and/or
      sequence variations in 3' untranslated regions. The number of genes having
      sequence variations between the rice cultivars and the functional implications of
      the identified SNPs are herein discussed.

PMID- 15500253
TI  - Mouse embryonic fibroblasts derived from Odin deficient mice display a
      hyperproliiferative phenotype.
AB  - Odin is a recently identified cytosolic phosphotyrosine binding (PTB) domain
      containing negative regulatory protein, that was discovered on the basis of its
      ability to undergo tyrosine phosphorylation upon stimulation by epidermal growth
      factor in HeLa cells. The protein was originally obtained as a KIAA clone (KIAA
      0229) from the Kazusa DNA Research Institute which maintains the HUGE protein
      database--a database devoted to the analysis of long cDNA clones encoding large
      proteins (>50 kDa). Odin has been demonstrated to cause downregulation of c-Fos
      promoter activity and to inhibit PDGF-induced mitogenesis in cell lines. To
      further investigate the role of Odin in growth factor receptor signaling and to
      elucidate its biological function in vivo, we have generated mice deficient in
      Odin by gene targeting. Odin-deficient mice do not display any obvious phenotype,
      and histological examination of the kidney, lung and liver does not show any
      major abnormalities as compared to wild-type controls. However, mouse embryonic
      fibroblasts (MEFs) generated from Odin-deficient mice exhibit a
      hyperproliferative phenotype compared to wild-type-derived MEFs, consistent with
      its role as a negative regulator of growth factor receptor signaling. Our results
      confirm that although Odin expression in mice is not essential for any major
      developmental pathway, it could play a significant functional role to negatively
      regulate growth factor receptor signaling pathways.

PMID- 15500254
TI  - A comprehensive approach for establishment of the platform to analyze functions
      of KIAA proteins II: public release of inaugural version of InGaP database
      containing gene/protein expression profiles for 127 mouse KIAA genes/proteins.
AB  - The inaugural version of the InGaP database (Integrative Gene and Protein
      expression database; http://www.kazusa.or.jp/ingap/index.html) is a comprehensive
      database of gene/protein expression profiles of 127 mKIAA genes/proteins related
      to hypothetical ones obtained in our ongoing cDNA project. Information about each
      gene/protein consists of cDNA microarray analysis, subcellular localization of
      the ectopically expressed gene, and experimental data using anti-mKIAA antibody
      such as Western blotting and immunohistochemical analyses. KIAA cDNAs and their
      mouse counterparts, mKIAA cDNAs, were mainly isolated from cDNA libraries derived
      from brain tissues, thus we expect our database to contribute to the field of
      neuroscience. In fact, cDNA microarray analysis revealed that nearly half of our
      gene collection is predominantly expressed in brain tissues. Immunohistochemical
      analysis of the mouse brain provides functional insight into the specific area
      and/or cell type of the brain. This database will be a resource for the
      neuroscience community by seamlessly integrating the genomic and proteomic
      information about the mouse KIAA genes/proteins.

PMID- 15500255
TI  - Determination of the capped site sequence of mRNA based on the detection of cap
      dependent nucleotide addition using an anchor ligation method.
AB  - The sequence analysis of the 5' ends of cDNAs prepared using the anchor ligation
      method has revealed that most of the full-length cDNAs have an additional dGMP at
      their 5' end that is absent in the corresponding genome sequence. Using model RNA
      transcripts with cap analogues possessing 7-methylguanosine and adenosine, the
      base of the added nucleotide has been shown to be complementary to the base of
      the cap analogue, suggesting that the cDNAs possessing an additional dGMP are
      derived from intact mRNAs with the cap structure. On the other hand, cap-free RNA
      did not produce cDNA with an extra dGMP. These findings suggest that we can
      determine whether or not the cDNA starts from the capped site sequence of mRNA
      based on the presence or absence of an additional dGMP at the 5' end of the cDNA
      synthesized using the anchor ligation method. This approach will be useful to
      determine the capped site sequence of mRNA, thus, to identify transcription start
      sites.

PMID- 15500256
TI  - Ginkgo biloba in Down Syndrome.

PMID- 15500257
TI  - Efficacy and tolerance of a comfrey root extract (Extr. Rad. Symphyti) in the
      treatment of ankle distorsions: results of a multicenter, randomized, placebo
      controlled, double-blind study.
AB  - Comfrey (Symphytum officinale L.) is a medicinal plant with anti-inflammatory,
      analgesic and tissue regenerating properties. In a double-blind, multicenter,
      randomized, placebo-controlled, group comparison study on patients suffering from
      unilateral acute ankle sprains (n = 142, mean age 31.8 years, 78.9% male), the
      percutaneous efficacy of an ointment of comfrey extract (Kytta-Salbe f, four
      treatments per day for 8 days) was confirmed decisively. Compared to placebo, the
      active treatment was clearly superior regarding the reduction of pain (tonometric
      measurement, p<0.0001, as the primary efficacy variable) and ankle edema (figure
      of-eight method, p = 0.0001). Statistically significant differences between
      active treatment and placebo could also be shown for ankle mobility (neutral zero
      method), and global efficacy. Under active treatment, no adverse drug reactions
      were reported. The good local and global tolerance of the trial medication could
      also be confirmed. The study results are consistent with the known pre-clinical
      and clinical data concerning comfrey.

PMID- 15500258
TI  - Protective effects of Choto-san and hooks and stems of Uncaria sinensis against
      delayed neuronal death after transient forebrain ischemia in gerbil.
AB  - Previously, we revealed that Choto-san (Diao-teng-san in Chinese), a Kampo
      formula, is effective on vascular dementia clinically, and the hooks and stems of
      Uncaria sinensis (Oliv.) Havil., a medicinal plant comprising Chotosan, has a
      neuroprotective effect in vitro. In the present study, for the purpose of
      clarifying their effects in vivo, we investigated whether the oral administration
      of Choto-san extract (CSE) or U. sinensis extract (USE) reduces delayed neuronal
      death following ischemia/reperfusion (i/rp) in gerbils. Transient forebrain
      ischemia was induced by bilateral carotid artery occlusion for 4 min, and two
      doses (1.0% and 3.0%) of CSE or USE were dissolved in drinking water and provided
      to the gerbils ad libitum from 7 days prior to i/rp until 7 days after i/rp. It
      was found that 1.0% and 3.0% CSE treatments significantly reduced pyramidal cell
      death in the hippocampal CA1 region at 7 days post i/rp. Three percent USE
      treatment also inhibited pyramidal cell death significantly at 7 days after i/rp.
      Superoxide anion and hydroxyl radical scavenging activities of the homogenized
      hippocampus at 7 days after i/rp in the 1.0% CSE- and 3.0% USE-treated groups
      were significantly enhanced compared to those of control. Further, lipid peroxide
      and NO2-/NO3- levels of the homogenized hippocampus at 48h after i/rp in the 1.0%
      CSE- and 3.0% USE-treated groups were significantly lower than those of control.
      These results suggest that the oral administration of CSE or USE provides a
      protective effect against transient ischemia-induced delayed neuronal death by
      reducing oxidative damage to neurons.

PMID- 15500259
TI  - Endothelium-dependent hypotensive and vasorelaxant effects of the essential oil
      from aerial parts of Mentha x villosa in rats.
AB  - Cardiovascular effects of an essential oil from the aerial parts of Mentha x
      villosa (OEMV) were tested in rats using a combined in vivo and in vitro
      approach. In non-anesthetized normotensive rats, OEMV (1, 5, 10, 20, 30 mg kg(-1)
      body wt., i.v.) induced a significant and dose-dependent hypotension (-3 +/-
      1.8%; -6 +/- 0.7%; -40 +/- 6.7%; -58 +/- 3.8%; -57 +/- 2.1%, respectively)
      associated with decreases in heart rate (-1 +/- 0.3%; -9 +/- 0.9%; -17 +/- 3.2%; 
      72 +/- 3.1%; -82 +/- 1.4%, respectively). The hypotensive and bradycardic
      responses evoked by OEMV were attenuated and blocke by pre-treatment of the
      animals with atropine (2 mg kg(-1) body wt., i.v.). In isolated rat atrial
      preparations, OEMV (10, 100, 300, 500 microg ml(-1)) produced concentration
      related negative chronotropic and inotropic effects (IC50 value = 229 +/- 17 and
      120 +/- 13 microg ml(-1), respectively). In isolated rat aortic rings, increasing
      concentrations of OEM (10, 100, 300, 500 microg ml(-1)) were able to antagonize
      the effects of phenylephrine (1 microM), prostaglandin F2alpha (10 microM) and
      KCl (80 mM)-induced contractions (IC50 value = 255 +/- 9, 174 +/- 4 and 165 +/-
      14 microg ml(-1), respectively). The vasorelaxant activity induced by OEMV was
      attenuated significantly by either endothelium removal (IC50 value = 304 +/- 9
      microg ml(-1)), NG-nitro L-arginine methyl ester (L-NAME) 100 microM (IC50
      value=359 +/- 18 microg ml(-1)), L-NAME 300 microM (IC50 value = 488 +/- 20
      microg ml(-1)) or indomethacin 10 microM (IC50 value = 334 +/- 18 microg ml(-1)).
      However, it was not affected by atropine 1 microM (IC50 value = 247 +/- 12 microg
      ml(-1)). Furthermore, the hypotensive response induced by OEMV was attenuated
      significantly after nitric oxide (NO) synthase blockade (L-NAME, 20 mg kg(-1)
      body wt., i.v.), while bradycardia was not altered. The results suggest that the
      hypotensive effect induced by OEMV is probably due to its direct cardiodepressant
      action and peripheral vasodilation, which can be attributed to both endothelium
      dependent (via EDRFs, at least NO and prostacyclin) and endothelium-independent
      mechanisms (such as Ca2+ channel blockade).

PMID- 15500260
TI  - Central nervous activity of elenoside.
AB  - Elenoside is a cytotoxic arylnapthalene lignan (NSC 644013-W/1) derived from
      Justicia hyssopifolia (Family: Acanthaceae). The neuropharmacological activity of
      this lignan, a beta-D-glucoside was studied. The LD50 (24 h) of elenoside in mice
      is 305 +/- 7 mg/kg by i.p. route. In the present study elenoside was given to
      rats at doses of 25 and 50 mg/kg, and its effects on locomotor activity (Varimex
      test), muscular relaxant activity, open-field test and with chlorpromazine, 10
      mg/kg was compared. On Varimex test, spontaneous activity was reduced. Elenoside
      produced a reduction in the permanence time on muscular relaxant activity
      (traction test). On open-field test, ambulation and rearing were reduced compared
      with the control group and an increase in boluses of dose-dependent rate was
      obtained. Thus it can be concluded that elenoside has central sedative effects
      and possible application in anxiety conditions.

PMID- 15500261
TI  - Studies on the anti-inflammatory and toxic effects of the stem bark of Khaya
      ivorensis (Meliaceae) on rats.
AB  - Khaya ivorensis A. Chev. (Meliaceae) is a common feature in anti-malarial recipe
      prescribed by African traditional medical practitioners. Investigations have
      proved that Khaya species possesses some level of anti-plasmodial activity. Anti
      inflammatory and toxicity studies were carried out on this plant using the Ugo
      Basile model 7140 and routine toxicity study methods, respectively, on adult
      wistar rats. The brain, spleen, heart, liver and kidneys were examined for
      dismorphological features, following oral administration of the ethanolic extract
      of K. ivorensis at the daily dose levels of 1000, 500 or 125 mg/kg for 7, 14 and
      7 days after cessation of drug administration. The study showed that tissue
      toxicity, especially neurotoxicity was dose dependent, similarly the anti
      inflammatory effect. The toxicity appeared to be reversible at lower doses. The
      wide margin between the therapeutic and toxic dosages makes the extract a
      possible safe drug in the management of malaria.

PMID- 15500262
TI  - Effects of Anoectochilus formosanus Hayata extract and glucocorticoid on lung
      maturation in preterm rats.
AB  - We investigated the effects of maternal administration of Anoectochilus
      formosanus extract and dexamethasone on lung maturation in preterm rats. A.
      formosanus group mothers were tube-fed A. formosanus extract (300 mg/kg body
      wt./day) for 7 days from days 12-18 of gestation. Dexamethasone group mothers
      were injected intraperitoneally with dexamethasone (0.2 mg/kg body wt.) in saline
      on day 18 of gestation. Control group mothers were similarly injected with saline
      alone. On day 19 of gestation, fetuses were delivered by cesarean section. A.
      formosanus treatment significantly increased the fetal lung/body weight ratio, as
      compared to dexamethasone treatment. Saturated phosphatidylcholine levels in
      fetal lung tissue and growth hormone levels in maternal serum were significantly
      increased in the A. formosanus- and dexamethasone-treated groups as compared to
      controls. The histological appearance of preterm rat lungs revealed extensive
      branching of intermediate airways, denser mesenchyme, and more epithelial tubules
      in the dexamethasone and A. formosanus groups as compared with the control group.
      These results suggest that antenatal A. formosanus treatment may play a role in
      accelerating fetal rat lung maturation.

PMID- 15500263
TI  - In vitro immunomodulatory activity of plants used by the Tacana ethnic group in
      Bolivia.
AB  - One hundred and seventy-eight ethanolic plant extracts from the pharmacopoeia of
      the Tacana, an ethnic group from Bolivia, were screened for immunomodulatory
      activity using complement cascade inhibition and ADP-induced platelet aggregation
      inhibition assays. Six impaired both complement pathways (classical and
      alternative): stem bark from Astronium urundeuvea (Anacardiaceae), Cochlospermum
      vitifolium (Cochlospermaceae), Terminalia amazonica (Combretaceae), Triplaris
      americana (Polygonaceae), Uncaria tomentosa (Rubiaceae) and Euterpe precatoria
      (Arecaceae) roots. Inhibition of complement cascade was independent of essential
      ion complexation, and was not due to direct hemolytic activity on target red
      blood cells. For A. urundeuvea, C. vitifolium, and T. amazonica, anti
      inflammatory activity relied on cyclo-oxygenase inhibition. Four of these species
      (A. urundeuva, T. americana, U. tomentosa and E. precatoria) are used
      traditionally to treat inflammatory processes.

PMID- 15500264
TI  - Comparative study of radical scavenger activities of crude extract and fractions
      from Cuphea carthagenensis leaves.
AB  - This study investigated the superoxide anion and hydroxyl radical scavenger
      properties, as well as the inhibition of lipid peroxidation by the crude
      hydroalcoholic extract (CE) and the butanolic (BF) and ethyl acetate (EAF)
      fractions of Cuphea carthagenensis leaves. In a enzymatic system of O2-
      production (xanthine/xanthine oxidase system) the CE, EAF and BF (0.1-100 microg
      ml(-1)) were effective at inhibiting both uric acid formation and NBT reduction
      by O2(-1). In the non-enzymatic system of O2- generation, the CE and fractions
      were effective only at the concentration of 100 microg ml(-1). The CE, EAF and BF
      were also evaluated for their ability to scavenge hydroxyl radicals and/or to
      chelate iron. The results showed that CE, BF and EAF from C. carthagenensis (0.1
      100 microg ml(-1)) were able to inhibit deoxyribose degradation in a
      concentration-dependent manner. CE was more potent than the fractions. In a
      hydrophobic system, increasing concentrations of CE, EAF and BF (0.1-100 microg
      ml(-1)) caused graded inhibition of lipid peroxidation of rat liver homogenate.
      The EAF displayed the lowest median inhibitory concentration. The present study
      suggests that an extract (CE) and fractions (EAF and BF) from C. carthagenensis
      leaves are significant sources of phenolic compounds with antioxidant activity in
      vitro and may have important health effects, for example, in cardiovascular
      disease.

PMID- 15500265
TI  - Studies on the aqueous extract of Terminalia chebula as a potent antioxidant and
      a probable radioprotector.
AB  - Aqueous extract of a natural herb, Terminalia chebula was tested for potential
      antioxidant activity by examining its ability to inhibit gamma-radiation-induced
      lipid peroxidation in rat liver microsomes and damage to superoxide dismutase
      enzyme in rat liver mitochondria. The antimutagenic activity of the extract has
      been examined by following the inhibition of gamma-radiation-induced strand
      breaks formation in plasmid pBR322 DNA. In order to understand the phytochemicals
      responsible for this, HPLC analysis of the extract was carried out, which showed
      the presence of compounds such as ascorbate, gallic acid and ellagic acid. This
      was also confirmed by cyclic voltammetry. The extract inhibits xanthine/xanthine
      oxidase activity and is also an excellent scavenger of DPPH radicals. The rate at
      which the extract and its constituents scavenge the DPPH radical was studied by
      using stopped-flow kinetic spectrometer. Based on all these results it is
      concluded that the aqueous extract of T. chebula acts as a potent antioxidant and
      since it is able to protect cellular organelles from the radiation-induced
      damage, it may be considered as a probable radioprotector.

PMID- 15500266
TI  - Anticholinesterase activity in an alkaloid extract of Huperzia saururus.
AB  - Huperzia saururus (Lam.) Trevis. (Lycopodiaceae) is used widely in Argentinian
      traditional medicine as an aphrodisiac and for memory improvement. An aqueous
      extract from the aerial parts was obtained by decoction, revealing the presence
      of alkaloids, among other constituents. By partition with organic solvent in
      alkaline media, alkaloids were extracted and then purified by gel permeation. We
      studied the anticholinesterase activity in vitro of the alkaloid extract using
      erythrocyte membranes and human serum as sources of acetylcholinesterase and
      pseudocholinesterase, respectively. The results show a marked inhibition of true
      acetylcholinesterase with an IC50 value of 0.58 microg/ml. Low inhibition of
      pseudocholinesterase was observed (IC50 value = 191 microg/ml). This shows a
      selectivity of the extract for the true acetylcholinesterase. Furthermore,
      chemical study of the bioactive extract was performed by GC-MS, revealing the
      presence of seven Lycopodium alkaloids, including some not identified previously:
      sauroxine, 6-hydroxylycopodine, N-acetyllycodine, lycopodine, lycodine, N
      methyllycodine, and clavolonine. Further investigations will be undertaken in
      order to discover which compound/s are responsible for the aqueous extract's
      acetylcholinesterase activity.

PMID- 15500267
TI  - Screening of Korean herbal medicines used to improve cognitive function for anti
      cholinesterase activity.
AB  - Methanolic extracts of seven herbs (Acorus calamus, Acorus gramineus, Bupleurm
      facaltum, Dioscorea batatas, Epimedium koreanum, Poria cocos and Zizyphi jujuba)
      used in traditional Korean medicine for improvement of memory and cognition in
      old age were tested for cholinesterase inhibitory properties using the Ellman
      colorimetric method. Significant inhibition of the enzyme at 200 microg/ml was
      observed for extracts from A. calamus and E. koreanum. The possible bases for the
      reputation of these and the other herbs tested are discussed in the light of
      previous investigations into their chemistry and biological activity.

PMID- 15500268
TI  - Effects of essential oil of Alpinia zerumbet on the compound action potential of
      the rat sciatic nerve.
AB  - Alpinia zerumbet, known popularly as "colonia" in Northeastern Brazil, is a
      medicinal plant that has been used widely in folk medicine as teas and infusions
      for the treatment of intestinal and cardiovascular diseases, including arterial
      hypertension. Our previous studies have demonstrated that the essential oil of A.
      zerumbet (OEAZ) is very active on excitable tissues, such as smooth muscle, and
      in this study we verified its effects on the compound action potential (CAP) of
      rat sciatic nerve. EOAZ induced a dose-dependent blockade of the CAP. Control
      peak-to-peak amplitude and conduction velocity of CAPs were 7.6 +/- 0.43 mV and
      80.6 +/- 3.19 m/s, respectively. At 60 microg/ml, EOAZ induced no demonstrable
      effect. Conduction velocity was significantly reduced at 180 min of preparation
      exposure to 100 microg/ml of EOAZ. At 300, 600 and 2000 microg/ml doses of EOAZ,
      the peak-to-peak amplitudes of CAPs following 180 min exposure of the nerve to
      the drug were reduced significantly, to 75.3 +/- 7.36%, 50.45 +/- 2.17% and 0%
      respectively, of control value. Conduction velocity was reduced significantly by
      300, 600 and 2000 microg/ml of EOAZ, at 180 min, to 83.61 +/- 3.28%, 64.06 +/-
      8.21% and 22.7 +/- 5.79%, respectively, of control value. All these effects
      developed slowly and were reversible upon a 180-min wash.

PMID- 15500269
TI  - Long-time health care leader Larry Sanders receives prestigious GHA Gold Honor
      Award.

PMID- 15500270
TI  - 2004 Chairman's Award: Athens Regional CEO John A. Drew, FACHE.

PMID- 15500271
TI  - 2004 Community Leadership Award: St. Joseph's/Candler's S.O.U.R.C.E. Program.

PMID- 15500272
TI  - Indigent care should be an equitably shared burden.

PMID- 15500273
TI  - U.S. Supreme Court wades into ERISA one more time.

PMID- 15500274
TI  - PHA develops visual educational tools to help hospital visitors and staff better
      understand the hospital culture.

PMID- 15500275
TI  - The truth about the Scruggs lawsuits.

PMID- 15500276
TI  - From Zurich to Sydney and back.

PMID- 15500277
TI  - G-scan--mobile multiview 3-D measuring system for the analysis of the face.
AB  - The development of optical 3-D measuring techniques and their use in industrial
      quality assurance, in design, and for rapid prototyping has experienced strong
      growth. A large number of optical 3-D measuring methods and systems are on the
      market in dentistry. CAD/CAM production has become firmly established in dental
      medicine, not least due to the systematic introduction of the Cerec technique and
      the digiDent method. The scanners on which these technologies are based are
      designed for a relatively small measuring area. To be able to measure and three
      dimensionally assess the face--and the numerous changes in the face/forehead/neck
      region--it was necessary to design and develop a self-calibrating measuring
      system with gray code for clinical use: the G-Scan measuring system. Objects up
      to a size of 500 x 500 x 400 mm can be acquired three-dimensionally with it, with
      a measuring inaccuracy of 10 to 70 microm in a typical measuring time of 15 s.
      The present article describes the measuring principle, the system parameters, and
      the features of the new measuring system, and illustrates the measuring results
      on 3-D displays of the face in static occlusion and in functional occlusion
      positions.

PMID- 15500278
TI  - Occlusal surface design with Cerec 3D.
AB  - Apart from the better visualization and simplified entry, the introduction of the
      new Cerec 3D software has also created new possibilities for designing the
      occlusal morphology. In this case, not only have the proven Extrapolation,
      Correlation and Function modes been improved and their use simplified, but an
      extension of these possibilities by combining different procedures has been
      introduced.

PMID- 15500279
TI  - 3D software extension for Cerec inLab.
AB  - Three new software components for the Cerec inLab system, already proven in the
      dental laboratory area, are presented. They are all based on three-dimensional
      display. On the one hand, the design can be simplified, and on the other hand,
      the range of indications can be extended to inlays, onlays, veneers, and
      multiunit bridges with the aid of these new components.

PMID- 15500280
TI  - Financing and organization of China's health care.

PMID- 15500281
TI  - Global warming kills trees, and people.

PMID- 15500282
TI  - Tackling health inequalities: new approaches in public policy.

PMID- 15500283
TI  - Secondary prevention of stroke--results from the Southern Africa Stroke
      Prevention Initiative (SASPI) study.
AB  - OBJECTIVE: To describe the prevalence of risk factors and experience of
      preventive interventions in stroke survivors, and identilfy barriers to secondary
      prevention in rural South Africa. METHODS: A clinician visited individuals in the
      Agincourt field site (in South Africa's rural north east) who were identified in
      a census as possible stroke victims to confirm the diagnosis of stroke. We
      explored the impact of stroke on the individual's family, and health-seeking
      behaviour following stroke by conducting in-depth interviews in the households of
      35 stroke survivors. We held two workshops to understand the knowledge,
      experience, and views of primary care nurses, who provide the bulk of
      professional health care. FINDINGS: We identified 103 stroke survivors (37 men),
      73 (71%) of whom had hypertension, but only 8 (8%) were taking anti-hypertensive
      treatment. Smoking was uncommon; 8 men and 1 woman smoked a maximum of ten
      cigarettes daily. 94 (91%) stroke survivors had sought help, which involved
      allopathic health care for most of them (81; 79%). 42 had also sought help from
      traditional healers and churches, while another 13 people had sought help only
      from those sources. Of the 35 survivors who were interviewed, 29 reported having
      been prescribed anti-hypertensive pills after their stroke. Barriers to secondary
      prevention included cost of treatment, reluctance to use pills, difficulties with
      access to drugs, and lack of equipment to measure blood pressure. A negative
      attitude to allopathic care was not an important factor. CONCLUSION: In this
      rural area hypertension is the most important modifiable risk factor in stroke
      survivors. Effective secondary prevention may reduce the incidence of recurrent
      strokes, but there is no system to deliver such care. New strategies for care are
      needed involving both allopathic and non-allopathic-health care providers.

PMID- 15500284
TI  - Cost-effectiveness of zinc as adjunct therapy for acute childhood diarrhoea in
      developing countries.
AB  - OBJECTIVE: To analyse the incremental costs, effects and cost-effectiveness of
      zinc used as adjunct therapy to standard treatment of acute childhood diarrhoea,
      including dysentery, and to reassess the cost-effectiveness of standard case
      management with oral rehydration salt (ORS). METHODS: A decision tree was used to
      model expected clinical outcomes and expected costs under four alternative
      treatment strategies. The best available epidemiological, clinical and economic
      evidence was used in the calculations, and the United Republic of Tanzania was
      the reference setting. Probabilistic cost-effectiveness analysis was performed
      using a Monte-Carlo simulation technique and the potential impacts of uncertainty
      in single parameters were explored in one-way sensitivity analyses. FINDINGS: ORS
      was found to be less cost-effective than previously thought. The use of zinc as
      adjunct therapy significantly improved the cost-effectiveness of standard
      management of diarrhoea for dysenteric as well as non-dysenteric illness. The
      results were particularly sensitive to mortality rates in non-dysenteric
      diarrhoea, but the alternative interventions can be defined as highly cost
      effective even in pessimistic scenarios. CONCLUSION: There is sufficient evidence
      to recommend the inclusion of zinc into standard case management of both
      dysenteric and non-dysenteric acute diarrhoea.A direct transfer of our findings
      from the United Republic of Tanzania to other settings is not justified, but
      there are no indications of large geographical differences in the efficacy of
      zinc. It is therefore plausible that our findings are also applicable to other
      developing countries.

PMID- 15500285
TI  - China's public health-care system: facing the challenges.
AB  - The severe acute respiratory syndrome (SARS) crisis in China revealed not only
      the failures of the Chinese health-care system but also some fundamental
      structural deficiencies. A decentralized and fragmented health system, such as
      the one found in China, is not well-suited to making a rapid and coordinated
      response to public health emergencies. The commercial orientation of the health
      sector on the supply-side and lack of health insurance coverage on the demand
      side further exacerbate the problems of the under-provision of public services,
      such as health surveillance and preventive care. For the past 25 years, the
      Chinese Government has kept economic development at the top of the policy agenda
      at the expense of public health, especially in terms of access to health care for
      the 800 million people living in rural areas. A significant increase in
      government investment in the public health infrastructure, though long overdue,
      is not sufficient to solve the problems of the health-care system. China needs to
      reorganize its public health system by strengthening both the vertical and
      horizontal connections between its various public health organizations. China's
      recent policy of establishing a matching-fund financed rural health insurance
      system presents an exciting opportunity to improve people's access to health
      care.

PMID- 15500286
TI  - Health in south-eastern Europe: a troubled past, an uncertain future.
AB  - The political and economic turmoil that occurred in south-eastern Europe in the
      last decade of the twentieth century left a legacy of physical damage. This
      aspect of the conflict has received considerable coverage in the media. However,
      surprisingly less has been reported about the effects of that turmoil on the
      health of the people living in the region. In an attempt to identify and
      synthesize data on these effects, we carried out a systematic review and used the
      results to put together a searchable online database of documents, reports, and
      published material, the majority of which have not previously been easily
      accessible (http:// www.lshtm.ac.uk/ecohost/see/index.php). The database covers
      the period from the early 1990s to 2003 and will be of considerable interest to
      policy-makers. It contains 762 items, many of them annotated and available for
      downloading. This paper synthesizes the main findings obtained from the material
      in the database and emphasizes the need for concerted action to improve the
      health of people in south-eastern Europe. Furthermore, we also recommend that
      agencies working in post-conflict situations should invest in developing and
      maintaining online databases that would be useful to others working in the area.

PMID- 15500287
TI  - Changing virulence of the SARS virus: the epidemiological evidence.

PMID- 15500288
TI  - Breaking the ice: HIV serostatus disclosure.

PMID- 15500289
TI  - Humanitarian catastrophe looms in Darfur.

PMID- 15500290
TI  - HIV/AIDS, hunger and malaria are the world's most urgent problems, say
      economists.

PMID- 15500291
TI  - Developing countries face double burden of disease.

PMID- 15500292
TI  - G-8 endorses new global HIV vaccine enterprise.

PMID- 15500293
TI  - Metastatic properties of prostate cancer cells are controlled by VEGF.
AB  - Mechanisms of metastasis, the major complication of prostate cancer, are poorly
      understood. In this study, we define molecular mechanisms that may contribute to
      the highly invasive potential of prostate cancer cells. Vascular endothelial
      growth factor (VEGF), its receptors (VEGFRs), and alpha5beta1 integrin were
      expressed by prostate cancer cells in vitro and by prostate tumors in vivo, and
      their expression was elevated at sites of bone metastasis compared to original
      prostate tumor. VEGF, through interaction with its receptors, regulated adhesive
      and migratory properties of the cancer cells. Specifically, the highly metastatic
      prostate cancer cell subline LNCaP-C4-2 showed a decreased adhesive but an
      enhanced migratory response to fibronectin, a ligand for alpha5beta1 integrin,
      compared to its nonmetastatic counterpart. A similar pattern was also observed
      when bone sialoprotein was used as a ligand in migration assays. Increased
      migration of metastatic prostate cancer cells to fibronectin and bone
      sialoprotein was regulated by VEGF via VEGFR-2. Tumor suppressor PTEN was
      involved in control of VEGF/VEGFR-2 stimulated prostate cancer cell adhesion as
      well as proliferation.

PMID- 15500294
TI  - Influence of retinoic acid on adhesion complexes in human hepatoma cells: a clue
      to its antiproliferative effects.
AB  - Retinoic acid exerts antiproliferative and differentiative effects in normal and
      transformed in vitro hepatocytes. In order to verify whether these effects are
      related to a modulation of adhesion molecules, we used Western blot analysis and
      immunofluorescence microscopy to investigate the E-cadherinl/beta-catenin
      complex, the main system of adherens junctions, and the occludin/ZO-1 complex
      present in the tight junctions in HepG2 cells cultured in the presence or absence
      of retinoic acid. Results showed that retinoic acid treatment increases the
      amount of beta-catenin bound to E-cadherin by decreasing its tyrosine
      phosphorylation level. Similar results were obtained with the tight junction
      system, in which the amount of occludin/ZO-1 complex is increased by a similar
      mechanism that reduced the level of ZO-1 phosphorylation on tyrosine.
      Immunofluorescence images also confirm these results, showing the localization on
      the cell surface of both adhesion complexes. Their insertion into the plasma
      membrane could be suggestive of an optimal reassembly and function of adherens
      and tight junctions in hepatoma cells, indicating that retinoic acid, besides
      inhibiting cell proliferation, improves cell-cell adhesion, sustaining or
      inducing the expression of a more differentiated phenotype.

PMID- 15500295
TI  - Retinaldehyde, a potent inhibitor of gap junctional intercellular communication.
AB  - Retinaldehyde and retinoic acid are derivatives of vitamin A, and retinaldehyde
      is the precursor for the synthesis of retinoic acid, a well-known inhibitor of
      gap junctional intercellular communication. In this investigation, we asked the
      question if retinaldehyde has similar effects on gap junctions. Gap junctional
      intercellular communication was measured by scrape-loading and preloading dye
      transfer methods, and studies were carried out mainly on cultured liver
      epithelial cells. Retinaldehyde was found to be a more potent inhibitor (dye
      transfer reduced by 50% at 2.8 microM) than retinoic acid (dye transfer reduced
      by 50% at 30 microM) and glycyrrhetinic acid (dye transfer reduced by 50% at 65
      microM). Both the 11-cis and all-trans forms of retinaldehyde were equally
      effective. Retinaldehyde inhibited dye transfer of both anionic Lucifer yellow
      and cationic Neurobiotin. Inhibition by retinaldehyde developed in less than two
      minutes at 50 microM, but unlike the reported case with retinoic acid, recovery
      was slower, though full. In addition to liver epithelial cells, retinaldehyde
      inhibited gap junctional communication in lens epithelial cells, retinal pigment
      epithelial cells and retinal ganglion cells.

PMID- 15500296
TI  - Transport features, reaction kinetics and receptor biomechanics controlling
      selectin and integrin mediated cell adhesion.
AB  - The distinct and overlapping roles of adhesion molecules belonging to the
      selectin and integrin families control the rate of leukocyte adhesion to
      stimulated vascular endothelial cells under hydrodynamic shear flow. Crystal
      structures have appeared for some of these interactions which complement
      molecular biology experiments, and clarify the molecular mechanism of the
      receptor-ligand binding interactions. Binding affinity data have also appeared
      using surface plasmon resonance and single-molecule biophysics experiments. These
      studies confirm and extend the predictions of previous experiments carried out in
      parallel-plate flow chambers, and cone and plate viscometers. This review
      discusses the current state of understanding on how molecular bond formation
      rates coupled with cellular and hydrodynamic features regulate leukocyte binding
      to endothelial cells.

PMID- 15500297
TI  - Recent findings in bipolar affective disorder.

PMID- 15500298
TI  - Twelve-month prevalence and disability of DSM-IV bipolar disorder in an
      Australian general population survey.
AB  - BACKGROUND: There have been few large-scale epidemiological studies which have
      examined the prevalence of bipolar disorder. The authors report 12-month
      prevalence data for DSM-IV bipolar disorder from the Australian National Survey
      of Mental Health and Well-Being. METHOD: The broad methodology of the Australian
      National Survey has been described previously. Ten thousand, six hundred and
      forty-one people participated. The 12-month prevalence of euphoric bipolar
      disorder (I and II)--similar to the euphoric-grandiose syndrome of Kessler and co
      workers--was determined. Those so identified were compared with subjects with
      major depressive disorder and the rest of the sample, on rates of co-morbidity
      with anxiety and substance use disorders as well as demographic features and
      measures of disability and service utilization. Polychotomous logistic regression
      was used to study the relationship between the three samples and these dependent
      variables. RESULTS: There was a 12-month prevalence of 0-5 % for bipolar
      disorder. Compared with subjects with major depressive disorder, those with
      bipolar disorder were distinguished by a more equal gender ratio; a greater
      likelihood of being widowed, separated or divorced; higher rates of drug abuse or
      dependence; greater disability as measured by days out of role; increased rates
      of treatment with medicines; and higher lifetime rates of suicide attempts.
      CONCLUSIONS: This large national survey highlights the marked functional
      impairment caused by bipolar disorder, even when compared with major depressive
      disorder.

PMID- 15500299
TI  - Higher socio-economic status of parents may increase risk for bipolar disorder in
      the offspring.
AB  - BACKGROUND: There are conflicting data regarding the socio-economic risk factors
      for bipolar disorders. The aim of the present study was to explore the
      association between the socio-economic status of an individual or the parent and
      the risk for bipolar disorder. METHOD: Two Danish registers were merged. From the
      data source, we extracted those born in 1960 or later, and those with a first
      ever admission to, or contact with, Danish psychiatric facilities during 1981
      1998 with a diagnosis of bipolar disorder. Fifty time-matched controls per case
      were chosen by the incidence-density sampling method. Effects of marital status,
      occupation, education, income, and wealth, of both subjects and the parents, were
      estimated using conditional logistic regression. RESULTS: A total of 947 cases
      were matched to 47 350 controls. Those at high risk of bipolar disorders were:
      single subjects, those in receipt of social assistance, pension or sickness
      payments, unemployed, subjects with a shorter educational history, and subjects
      with lower income. Conversely, parental higher education and higher level of
      paternal wealth were associated with increased risk. These associations remained
      significant after adjustment for gender, family history of psychiatric diagnoses,
      and other socio-economic variables, and are unlikely to be explained by known
      biases. CONCLUSIONS: The associations of lower socio-economic indices of subjects
      may be explained as a consequence of the disease. The association of higher socio
      economic indices of parents may be explained by socio-economic achievement in the
      family of origin.

PMID- 15500300
TI  - Behavioural and neurocognitive responses to sad facial affect are attenuated in
      patients with mania.
AB  - BACKGROUND: The processing of facial emotion involves a distributed network of
      limbic and paralimbic brain structures. Many of these regions are also implicated
      in the pathophysiology of mood disorders. Behavioural data indicate that
      depressed subjects show a state-related positive recognition bias for faces
      displaying negative emotions. There are sparse data to suggest there may be an
      analogous, state-related negative recognition bias for negative emotions in
      mania. We used functional magnetic resonance imaging (fMRI) to investigate the
      behavioural and neurocognitive correlates of happy and sad facial affect
      recognition in patients with mania. METHOD: Functional MRI and an explicit facial
      affect recognition task were used in a case-control design to measure brain
      activation and associated behavioural response to variable intensity of sad and
      happy facial expressions in 10 patients with bipolar I mania and 12 healthy
      comparison subjects. RESULTS: The patients with mania had attenuated subjective
      rating of the intensity of sad facial expressions, and associated attenuation of
      activation in the subgenual anterior cingulate and bilateral amygdala, with
      increased activation in the posterior cingulate and posterior insula. No
      behavioural or neurocognitive abnormalities were found in response to
      presentation of happy facial expressions. CONCLUSIONS: Patients with mania showed
      a specific, mood-congruent, negative bias in sad facial affect recognition, which
      was associated with an abnormal profile of brain activation in paralimbic regions
      implicated in affect recognition and mood disorders. Functional imaging of facial
      emotion recognition may be a useful probe of cortical and subcortical
      abnormalities in mood disorders.

PMID- 15500301
TI  - The effects of emotional salience on thought disorder in patients with bipolar
      affective disorder.
AB  - BACKGROUND: This study aimed to explore the effects of emotionally salient
      material on thought disorder in patients with bipolar affective disorder. METHOD:
      Seventy-one participants (20 manic, 15 depressed, 16 currently well patients and
      20 non-psychiatric-controls) were interviewed in two conditions: an emotionally
      salient interview and a non-salient interview. Speech samples were rated using
      the Scale for the Assessment of Thought, Language and Communication. RESULTS:
      Manic patients presented with significantly more thought disorder than any other
      group in both conditions and exhibited the greatest reaction to emotionally
      salient material. CONCLUSION: The effects of emotional salience on thought,
      language and communication are not unique to schizophrenic patients. The speech
      of manic patients is more affectively responsive than the speech of remitted,
      bipolar depressed and normal participants. The implications of these findings are
      discussed.

PMID- 15500302
TI  - Effect of symptoms on executive function in bipolar illness.
AB  - BACKGROUND: The relationship between cognitive function and symptomatology in
      bipolar disorder is unclear. This study assessed executive function during the
      manic, depressed and remitted stages of bipolar I disorder. METHOD: Tasks
      assessing phonological and semantic verbal fluency, the Hayling Sentence
      Completion Test, the Stroop Neuropsychological Screening Test and the Cognitive
      Estimates Test were administered to manic (n = 15), depressed (n = 15), and
      remitted (n = 15) bipolar I patients, and to healthy controls (n = 30). Multiple
      regression analyses and analyses of covariance were used to identify potential
      determinants of executive dysfunction in the three bipolar groups. RESULTS:
      Executive function deficits were particularly associated with the manic state. In
      general, manic patients performed less accurately than the remitted and depressed
      groups, and their performance deficit was related to the severity of positive
      thought disorder. The depressed and remitted bipolar groups showed a less
      widespread pattern of impairment. Deficits in response initiation, strategic
      thinking and inhibitory control were evident in all the bipolar groups.
      CONCLUSIONS: Executive function deficits in bipolar I disorder are most evident
      during mania, and are particularly associated with formal thought disorder.
      However, deficits in response initiation, strategic thinking and inhibitory
      control may be more related to the underlying disorder than a particular symptom
      profile.

PMID- 15500303
TI  - Characteristics of non-verbal memory impairment in bipolar disorder: the role of
      encoding strategies.
AB  - BACKGROUND: There is evidence that individuals with bipolar disorder exhibit
      neuropsychological impairments not only during episodes of depression or mania
      but also when they are euthymic. One of the most consistently reported cognitive
      problems in euthymic individuals with bipolar disorder is impairment in episodic
      memory. Learning and memory depend on individuals' ability to organize
      information during learning. A recent study by our group showed that verbal
      episodic memory impairments in euthymic patients with bipolar I disorder (BP-I)
      are mediated by difficulties in organizing verbal information appropriately
      during learning. The purpose of the present study was to determine whether memory
      impairments in euthymic individuals with BP-I extend to non-verbal memory and
      whether non-verbal memory impairments are mediated by difficulties in organizing
      non-verbal information during encoding. METHOD: Study participants were 25
      euthymic, remitted individuals with BP-I and 25 age, gender and education matched
      control participants. Participants completed the Rey-Osterrieth Complex Figure
      Test (RCFT), a well-established measure of non-verbal memory that enables
      assessment of organization during learning. RESULTS: Compared to control
      participants, BP-I participants showed impaired performance on the RCFT immediate
      recall. They also relied less on organizational strategies during encoding.
      Multiple regression modeling indicated that group differences between control and
      BP-I participants in long-delayed free recall did not remain statistically
      significant when effects of lower organization were partialled out. CONCLUSIONS:
      Non-verbal memory problems in individuals with bipolar disorder, while euthymic,
      are mediated by poor use of non-verbal organization strategies during encoding,
      but do not appear to reflect deficits in retention of information.

PMID- 15500304
TI  - Marked increases in psychopathology found in a 30-year cohort comparison of
      suicide attempters.
AB  - BACKGROUND: Although several epidemiological studies have found increases in the
      percentages of people who have made a suicide attempt, few cohort comparisons
      have been conducted to determine changes within this population over time. The
      purpose of this investigation was to determine if there have been changes in the
      clinical profile of suicide attempters in recent decades. METHOD: Comparisons
      between a sample of 258 suicide attempters evaluated between 1970 and 1973 and a
      second sample of 179 suicide attempters evaluated between 1999 and 2002 were made
      on depression, hopelessness, suicide intent, drug use, history of suicide
      attempts and subsequent suicide attempts. RESULTS: Present-day suicide attempters
      were found to exhibit greater levels of depression (p = 0.031), hopelessness (p =
      0.008), suicide intent (p < 0.001), and had much higher rates of illicit drug use
      (p < 0.001). Almost twice as many of the present-day suicide attempters had
      histories of four or more suicide attempts (p < 0.001), and the present-day
      suicide attempters made subsequent suicide attempts at close to four times the
      rate in the year following the index attempt (p < 0.001). CONCLUSIONS: The
      present-day suicide attempters exhibited greater levels of psychopathology on
      every major variable assessed. Replication is necessary and public health
      implications are discussed.

PMID- 15500305
TI  - What predicts suicide attempts in women with eating disorders?
AB  - BACKGROUND: Suicide is a common cause of death in anorexia nervosa and suicide
      attempts occur often in both anorexia nervosa and bulimia nervosa. No studies
      have examined predictors of suicide attempts in a longitudinal study of eating
      disorders with frequent follow-up intervals. The objective of this study was to
      determine predictors of serious suicide attempts in women with eating disorders.
      METHOD: In a prospective longitudinal study, women diagnosed with either DSM-IV
      anorexia nervosa (n = 136) or bulimia nervosa (n = 110) were interviewed and
      assessed for suicide attempts and suicidal intent every 6-12 months over 8.6
      years. RESULTS: Fifteen percent of subjects reported at least one prospective
      suicide attempt over the course of the study. Significantly more anorexic (22.1%)
      than bulimic subjects (10.9%) made a suicide attempt. Multivariate analyses
      indicated that the unique predictors of suicide attempts for anorexia nervosa
      included the severity of both depressive symptoms and drug use over the course of
      the study. For bulimia nervosa, a history of drug use disorder at intake and the
      use of laxatives during the study significantly predicted suicide attempts.
      CONCLUSIONS: Women with anorexia nervosa or bulimia nervosa are at considerable
      risk to attempt suicide. Clinicians should be aware of this risk, particularly in
      anorexic patients with substantial co-morbidity.

PMID- 15500306
TI  - Therapist competence and clinical outcome in the Prevention of Parasuicide by
      Manual Assisted Cognitive Behaviour Therapy trial: the POPMACT study.
AB  - BACKGROUND: Therapist competence may be an important factor in determining
      clinical outcome in psychological therapies. However, there are few published
      studies of therapist competence v. patient outcome from randomized controlled
      trials. We tested the hypothesis that higher levels of therapist competence would
      lead to better clinical outcomes in both patient- and observer-rated measures at
      6- and 12-month follow-up. METHOD: A random sample of 49 audiotapes of manual
      assisted cognitive therapy sessions delivered by 21 therapists involved in the
      Prevention of Parasuicide by Manual Assisted Cognitive Behaviour Therapy trial
      was rated to assess the level of therapist competence. Patient outcome was
      assessed using self and observer ratings of depressive and anxiety symptoms,
      social functioning, global functioning and number of episodes of deliberate self
      harm. RESULTS: At 6-month follow-up, there was a statistically significant
      association between therapist level of competence and observer-rated depression
      only. At 12-month follow-up, significant associations were noted between
      therapist competence and all observer-rated clinical outcomes but not for self
      rated outcome measures. However, there was no association between therapist
      competence and the number of self-harm episodes during follow-up. CONCLUSIONS:
      When treated by therapists rated as more competent than other therapists who
      received equivalent brief training, patients with recurrent self-harm show
      significant clinical improvements. However, this benefit is not identified across
      all outcome measures and is not fully apparent until 12-month follow-up.

PMID- 15500307
TI  - Defining nicotine dependence for genetic research: evidence from Australian
      twins.
AB  - BACKGROUND: Whether current criteria used to define nicotine dependence are
      informative for genetic research is an important empirical question. The authors
      used items of the DSM-IV and of the Heaviness of Smoking Index to characterize
      the nicotine dependence phenotype and to identify salient symptoms in a
      genetically informative community sample of Australian young adult female and
      male twins. METHOD: Phenotypic and genetic factor analyses were performed on nine
      dependence symptoms (the seven DSM-IV substance dependence criteria and the two
      Heaviness of Smoking Index (HSI) items derived from the Fagerstrom Tolerance
      Questionnaire, time to first cigarette in the morning and number of cigarettes
      smoked per day). Phenotypic and genetic analyses were restricted to ever smokers.
      RESULTS: Phenotypic nicotine dependence symptom covariation was best captured by
      two factors with a similar pattern of factor loadings for women and men. In
      genetic factor analysis item covariation was best captured by two genetic but one
      shared environmental factor for both women and men; however, item factor loadings
      differed by gender. All nicotine dependence symptoms were substantially
      heritable, except for the DSM-IV criterion of 'giving up or reducing important
      activities in order to smoke', which was weakly familial. CONCLUSIONS: The
      salient behavioral indices of nicotine dependence are similar for women and men.
      DSM-IV criteria of tolerance, withdrawal, and experiencing difficulty quitting
      and HSI items time to first cigarette in the morning and number of cigarettes
      smoked per day may represent the most highly heritable symptoms of nicotine
      dependence for both women and men.

PMID- 15500308
TI  - The relationship of tobacco smoking with depressive symptomatology in the Third
      Mexican National Addictions Survey.
AB  - BACKGROUND: While an association between cigarette smoking and depression has
      been established in Anglo populations, replication of tobacco-depression
      associations in countries where smoking is growing may provide important new
      insights. The objectives of this study were to estimate the association of
      depressive symptomatology with tobacco smoking, number of cigarettes smoked
      daily, and smoking cessation in a representative sample of the Mexican
      population. METHOD: The data come from the Third National Addictions Survey
      (1998) conducted by the Mexican Ministry of Health, representative of Mexico's
      civilian population residing in cities and towns with 2500+ inhabitants, aged 18
      64. Part of a multi-stage, stratified, probability sample, 1935 men and women
      answered a version of the survey that also included the CES-D depression scale.
      Analyses addressed the survey's complex design and controlled for income and
      educational evel. RESULTS: Among women only, current smokers had twice the odds
      of elevated depressive symptomatology than never smokers (OR 2.1, 95% CI 1.3-3.5,
      p = 0.002). For men, only those smoking a pack or more a day had greater odds of
      depressive symptomatology (OR 5.9, 95% CI 1.6-21.9, p = 0.008). Overall, former
      smokers who ceased smoking within 6 months had lower odds of depressive
      symptomatology than current smokers (OR 0.4, 95% CI 0.1-1.0, p = 0.042).
      CONCLUSIONS: These findings add to the accumulating evidence for the association
      between smoking and depression in different cultures and populations.

PMID- 15500309
TI  - Estimating post-traumatic stress disorder in the community: lifetime perspective
      and the impact of typical traumatic events.
AB  - BACKGROUND: Community surveys have assessed post-traumatic stress disorder (PTSD)
      in relation to traumatic events designated by respondents as the worst they have
      ever experienced. An assessment of PTSD in relation to all reported traumas would
      impose too great a burden on respondents, a considerable proportion of whom
      report multiple traumas. The 'worst event' method is efficient for identifying
      persons with PTSD, but may overestimate the conditional probability of PTSD
      associated with the entire range of PTSD-level traumas. In this report, we
      evaluate this potential bias. METHOD: The Detroit Area Survey of Trauma (n =
      2181) estimated the PTSD risk from two samples of traumas: (1) a representative
      sample of traumas formed by selecting a random trauma from each respondent's list
      of traumas; and (2) traumas designated by respondents as the worst (the standard
      method). RESULTS: Both estimation methods converged on key findings, including
      identifying trauma types with the highest probability of PTSD and sex differences
      in the risk of PTSD. Compared to the random events, the 'worst event' method
      yielded a moderately higher conditional probability for PTSD (0.136 v. 0.092).
      The bias was due almost entirely to the deviation of the distribution of the
      worst events from expected values, if all event types had equal prior selection
      probabilities. Direct adjustment, setting the distribution equal to expected
      values and applying the observed probabilities of PTSD associated with individual
      event types brought the estimate close to the unbiased estimate, based on the
      randomly selected traumas. CONCLUSIONS: Only the 'worst event' method can be used
      as a short-cut to assessing all traumas. The bias in the estimated risk of PTSD
      is modest and is attenuated by direct adjustment.

PMID- 15500310
TI  - Trauma, time and mental health: a study of temporal reintegration and Depressive
      Disorder among Southeast Asian refugees.
AB  - BACKGROUND: Prior research suggested that time splitting--suppressing the past
      and dissociating it from present and future--protected refugee mental health in
      the aftermath of catastrophe. The current study investigates temporal
      reintegration, defined as cognitive recapture of the past and reconnecting it
      with present and future, the mental health effects of temporal reintegration, and
      factors moderating the associated risk for Depressive Disorder. METHOD: A
      community sample of 608 Southeast Asian refugees, resettled in Vancouver British
      Columbia between 1979 and 1981, were interviewed on three separate occasions over
      a 10-year period. Participants performed a temporal orientation task and
      responded to questions about employment, social relations and mental health.
      Depressive Disorder, measured by a typology derived from Grade of Membership
      analysis of symptoms, constituted the dependent variable. Latent Growth Curve
      Analysis was used to examine both levels and rates of change in the probability
      of Depressive Disorder as predicted by changes in temporal reintegration, as well
      as the contribution of putative social and psychological moderators to explaining
      variations in growth parameters. RESULTS: Time relatedness increased over the
      duration of the study. Temporal reintegration jeopardized mental health.
      Employment and relational stability each moderated the mental health effects of
      temporal reintegration. CONCLUSIONS: Although time splitting may be effective in
      coping with adversity over the short-term, eventual temporal reintegration is
      probably ineluctable. Stability in love and work are protective factors,
      mitigating the mental health vicissitudes of temporal reintegration. Implications
      for optimal timing of clinical interventions are discussed.

PMID- 15500311
TI  - Measuring empathy: reliability and validity of the Empathy Quotient.
AB  - BACKGROUND: Empathy plays a key role in social understanding, but its empirical
      measurement has proved difficult. The Empathy Quotient (EQ) is a self-report
      scale designed to do just that. This series of four studies examined the
      reliability and validity of the EQ and determined its factor structure. METHOD:
      In Study 1, 53 people completed the EQ, Social Desirability Scale (SDS) and a non
      verbal mental state inference test, the Eyes Task. In Study 2, a principal
      components analysis (PCA) was conducted on data from 110 healthy individuals and
      62 people reporting depersonalisation (DPD). Approximately 1 year later, Study 3,
      involved the re-administration of the EQ (n = 24) along with the Interpersonal
      Reactivity Index (IRI; n = 28). In the last study, the EQ scores of those with
      DPD, a condition that includes a subjective lack of empathy, were examined in
      depth. RESULTS: An association was found between the Eyes task and EQ, and only
      three EQ items correlated with the SDS. PCA revealed three factors: (1)
      'cognitive empathy'; (2) 'emotional reactivity', and (3) 'social skills'. Test
      retest reliability was good and moderate associations were found between the EQ
      and IRI subscales, suggesting concurrent validity. People with DPD did not show a
      global empathy deficit, but reported less social competence. CONCLUSIONS: The EQ
      is a valid, reliable scale and the different subscales may have clinical
      applications.

PMID- 15500312
TI  - Temporal stability of saccadic task performance in schizophrenia and bipolar
      patients.
AB  - BACKGROUND: Identifying endophenotypes of schizophrenia will assist in the
      identification of individuals who are at heightened risk for the disorder.
      Investigators have proposed antisaccade task deficits as an endophenotypic marker
      of schizophrenia. However, the diagnostic specificity and the temporal stability
      of the task deficit are unresolved issues. To date, there are few published
      reports of test-retest stability of antisaccade task performance in psychiatric
      patients. METHOD: Twenty-three schizophrenia out-patients and 10 bipolar out
      patients were administered two saccadic (antisaccade and refixation) tasks at two
      separate assessments, with an average test retest interval of 33 months. RESULTS:
      The schizophrenia patients displayed high test-retest reliabilities of
      antisaccade task accuracy, despite changes in medication and clinical status.
      Additionally, the schizophrenia group's saccadic reaction times for antisaccade
      correct responses and task errors were moderately stable over time. In contrast,
      the bipolar patients did not show temporal stability in their antisaccade task
      accuracy or in their response latencies to either correct or incorrect
      antisaccade responses. CONCLUSIONS: The results are supportive of the trait-like
      characteristics of antisaccade task deficits in schizophrenia patients. These
      findings also suggest that antisaccade task deficits may serve as an
      endophenotypic marker of schizophrenia.

PMID- 15500313
TI  - The Social, Genetic and Developmental Psychiatry Centre: its origins, conception
      and initial accomplishments.
AB  - BACKGROUND: The Social, Genetic and Developmental Psychiatry Centre was
      established by the Medical Research Council, in partnership with the Institute of
      Psychiatry, King's College London, in 1994. METHOD AND RESULTS: The paper
      describes the origins of the Centre; the reasons why a new initiative was needed
      in the early 1990s; the thinking that led to the proposal for a major
      interdisciplinary research centre that integrated social, genetic and
      developmental research perspectives; the approach to international recruitment of
      world leaders; and the initial research accomplishments with respect to the basic
      goal of understanding nature-nurture interplay. CONCLUSIONS: The structure and
      interdisciplinary approach of the Centre have proved a success and the initial
      accomplishments have begun to meet the objectives of showing how nature-nurture
      interplay is involved in the development of psychiatric disorders.

PMID- 15500314
TI  - First structurally characterized actinide isocyanates.
AB  - The synthesis and characterization of the neutral uranylisocyanate
      UO(2)(NCO)(2)(OP(NMe(2))(3))(2) [crystal data: monoclinic, P2(1)/c, a = 8.512(2)
      A, b = 10.931(2) A, c = 14.329(3) A, beta = 103.923(3) degrees , V = 1294.0(4)
      A(3), Z = 2] and isocyanato uranate (Et(4)N)(6)[(UO(2))(2)(NCO)(5)O](2) x
      2CH(3)CN x H(2)O [crystal data: monoclinic, P2(1)/c, a = 17.2787(2) A, b =
      15.560(1) A, c = 32.7619(4) A, beta = 94.0849(5) degrees , V = 8786.5(2) A(3), Z
      = 4] are reported. Not only are these compounds the first unambiguously
      characterized uranium isocyanates regardless of the oxidation state for uranium,
      but they are also the first structurally characterized actinide isocyanates. Both
      compounds show coordination of the OCN moiety through nitrogen to uranium and
      were characterized using IR and (1)H, (13)C, (14)N, and (31)P NMR spectroscopy
      and X-ray diffraction.

PMID- 15500315
TI  - DFT study on the five isomers of PW(12)O(40)(3)(-): relative stabilization upon
      reduction.
AB  - The electronic characteristics and the redox properties of each isomer of
      PW(12)O(40)(3)(-) depend on the arrangement adopted by the metal-oxide framework.
      At the DFT/BP86 level, we computed the structures of the five isomers of
      PW(12)O(40)(3)(-) in oxidized form. The energy scale fits the experimental
      findings as well as the number of rotated triads of the metal-oxide core since
      the energy grows as follows: alpha < beta < gamma < delta < epsilon. The reduced
      clusters behave differently as long as the beta form becomes the most stable
      isomer after the second reduction. The gamma isomer also gains stability upon
      reduction, but not enough to be competitive with beta. For the 4-fold reduced
      PW(12) cluster, the energy difference computed between beta and gamma in solution
      is 11 kcal mol(-)(1). This large difference proves that the beta --> gamma
      isomerization is not favored upon simple reduction. The other isomers, delta and
      epsilon, are much more unstable than alpha or beta in any reduction state.

PMID- 15500316
TI  - Formation of one-dimensional metal-water chain containing cyclic water hexamers.
AB  - Cyclic water hexamers containing 1-D metal--water chains have been observed in
      the complexes of [M(H(2)biim)(2)(OH(2))(2)](ina)(2) x 4H(2)O [M = Zn (1) and Co
      (2), H(2)biim = 2,2'-biimidazole, ina = isoniconate]. The water clusters are
      trapped by the cooperative association of coordination interactions as well as
      hydrogen bonds.

PMID- 15500317
TI  - Quantitative photochemistry of Cp'Pt(CH(3))(3) (Cp' = eta(5)-C(5)H(4)CH(3)) in
      solution: a highly efficient organometallic photoinitiator for hydrosilylation.
AB  - The quantitative photochemistry of the platinum organometallic complex,
      Cp'Pt(CH(3))(3) (Cp' = eta(5)-C(5)H(4)CH(3)), has been investigated in
      methylcyclohexane and n-pentane solutions at 293 K following UV irradiation into
      the lowest lying absorption bands. Absolute photochemical quantum efficiency
      (phi(cr)) results obtained for Cp'Pt(CH(3))(3) at 313 and 366 nm reveal that the
      system very effectively photoreacts with phi(cr) = 0.34-0.41 in these solvents
      and 0.79-0.85 when 53 mM Et(3)SiH is incorporated. These photoefficiencies
      indicate that the quantitative photochemistry is 2 orders of magnitude higher
      than previously recognized. The application of Cp'Pt(CH(3))(3) as an effective
      photoinitiator for hydrosilylation reactions involving vinyl/hydride silicone
      mixtures is demonstrated.

PMID- 15500318
TI  - Interwoven 2-D coordination network prepared from the molecular host
      tris(isonicotinoyl)cyclotriguaiacylene and silver(I) cobalt(III)
      bis(dicarbollide).
AB  - A new 3-fold symmetric molecular host, tris(isonicotinoyl)cyclotriguaiacylene,
      has been synthesized from cyclotriguaiacylene and isonicotinoyl chloride
      hydrochloride in 70% yield. Its crystal structure shows dimerization of the host
      molecules into a capsule-like arrangement. When reacted with
      Ag[Co(C(2)B(9)H(11))(2)], the host forms a 1-D [ML(2)](n) coordination polymer,
      which assembles into a 2-D interwoven network through a similar dimerization of
      the host moieties around acetonitrile guests. Thus, the network structure
      represents an elegant example whereby the solid state structure of the building
      blocks is echoed in the resulting supramolecular assembly. The 2-D sheets are
      further stabilized by pi...pi stacking interactions between pyridyl donors of
      alternate 1-D coordination polymers.

PMID- 15500319
TI  - Observation of hysteretic bistability in [Co(III)Cp(2)](+)[Fe(III)I(4)](-).
AB  - [Co(III)Cp(2)](+)[Fe(III)I(4)](-) (Cp = cyclopentadienyl) prepared by the double
      oxidation of FeI(2) and CoCp(2) with iodine exhibits a 30 degrees C thermal
      hysteresis in magnetic susceptibility between 134 and 164 K that is attributed to
      a phase transition to a disordered triclinic unit cell from an ordered monoclinic
      unit cell upon cooling.

PMID- 15500320
TI  - 1-D infinite array of metalloporphyrin cages.
AB  - The reaction of Co(II) with 5,15-dipyridyl-10,20-diphenylporphyrin (H(2)DPyP)
      produces the first metal-organic coordination polymer supported by a trans meso
      bifunctional porphyrin ligand. Formulated empirically as [Co(3)(DPyP)(3)] x 4DMF,
      this compound exhibits a ribbonlike coordination network consisting of
      tetranuclear metalloporphyrin cages. The DMF guest molecules fill the intra
      ribbon cages as well as the inter-ribbon space. Evacuation of [Co(3)(DPyP)(3)] x
      4DMF at 130 degrees C generates [Co(3)(DPyP)(3)] that retains crystallinity, as
      shown by its powder X-ray diffraction pattern, which is consistent with that of
      [Co(3)(DPyP)(3)] x 4DMF.

PMID- 15500321
TI  - A three-dimensional, noninterpenetrating metal--organic framework with the
      moganite topology: a simple (4(2)x6(2)x8(2))(4x6(4)x8)(2) net containing two
      kinds of topologically nonequivalent points.
AB  - Self assembly of Cu(2+) with the multifunctional ligand 2-(4-pyridyl)thiazole-4
      carboxylic acid (Pytac) affords the neutral 3D coordination polymer
      [Cu(3)(Pytac)(6)](H(2)O)(14) (hereafter, SZL-1), which has the rare moganite
      topology. The mineral moganite has a topology that is closely related to the well
      known quartz topology, but the two topologies are differentiated by the number of
      topologically inequivalent nodes. Whereas only one kind of node is present in
      quartz, two types of topologically inequivalent nodes are present in moganite.
      The title compound, which has three vertices in its repeat unit, has two types of
      topologically inequivalent nodes with the overall vertex symbol
      (4(2)x6(2)x8(2))(4x6(4)x8)(2) corresponding to the moganite net. Prior to this
      report, few metal-organic framework materials (MOFs) have been found to contain
      more than one type of node, and SZL-1 is the first MOF with the moganite
      topology.

PMID- 15500322
TI  - Low-dimensional hybrid copper halides with novel D6R Cu(6)I(6) cores.
AB  - Two low-dimensional hybrid copper halides, (2,2'-bipy)Cu(3)I(3) (1) and (2,2'
      bipy)Cu(4)I(4) (2) (2,2'-bipy = 2,2'-bipyridine), with novel D6R (double six
      membered rings) Cu(6)I(6) cores were synthesized by hydro(solvo)thermal reactions
      and characterized by single-crystal X-ray diffraction.

PMID- 15500323
TI  - Structure of a discrete hexadecameric water cluster in a metal-organic framework
      structure.
AB  - Pyrazine-2,3,5,6-tetracarboxylic acid (pytcH(4)) reacts with Cu(NO(3))(2)x6H(2)O
      in 1:2 molar ratio in the presence of pyridine (py) vapor to form blue crystals
      of a coordination polymer with the empirical formula [Cu(2.5)(pytc)(py)(8)(NO(3)(
      ))x10H(2)O](n). Four such polymeric chains gather around a hexadecameric water
      cluster to form an overall 3D metal-organic framework structure. Once the water
      molecules are removed, the 3D structure breaks down. It presents a new mode of
      association of water molecules not predicted theoretically or found
      experimentally.

PMID- 15500324
TI  - In situ reduction of copper(II) forming an unusually air stable linear complex of
      copper(I) with a fluorescent tag.
AB  - A new fluorescent ligand (phi(f) = 0.8 in dioxane), 2-(4'
      aminophthalimidomethyl)pyridine (L), has been synthesized. A one-pot synthesis of
      its copper(I) complex upon reduction of copper(II) is achieved at room
      temperature. This complex, which has been characterized by X-ray crystallography,
      shows a linear N-Cu-N geometry with Cu-N bond lengths of 1.89 A. X-ray structure
      reveals weak Cu...O interactions between copper and one of the imide oxygen atoms
      of the ligand framework. Additional weak Cu...O interactions between copper and
      oxygen atoms of the ClO(4)(-) counteranion are detected that lead to a zigzag
      polymeric chain with alternate ClO(4)(-) and copper ions. A 2-D intermolecular
      hydrogen bonding network is also observed. This complex is found to be highly
      inert toward oxidation both in the solid state and in solution.

PMID- 15500325
TI  - [(IMo(7)O(26))(2)](6)(-): A missing link between molecular and solid oxides.
AB  - A new molecular oxide, [(IMo(7)O(26))(2)](6)(-), that has a self-contained
      structure has been synthesized. Its structural relevance both to the rutile
      structure and several molecular oxides that had been classified as "strange ones
      with odd structures" has given some insights as to why those species assume such
      structures. The novel yet self-contained nature of the structure suggests the
      existence of a new class of molecular oxides of related structures.

PMID- 15500327
TI  - One-dimensional octacyanomolybdate-based Cu(II)--Mo(V) bimetallic assembly with a
      novel rope-ladder chain structure.
AB  - A new type of one-dimensional cyanide-bridged Cu(II)--Mo(V) bimetallic assembly,
      [Cu(cyclam)](3)[Mo(CN)(8)](2)x5H(2)O (cyclam = 1,4,8,11
      tetraazacyclotetradecane), was prepared by self-assembling Mo(CN)(8)(3)(-) and
      Cu(cyclam)(2+) ions in a 2:3 stoichiometric ratio. The overall molecular view is
      delineated as a novel rope-ladder chain structure. It displays a dominant
      ferromagnetic behavior within a pentanuclear Cu(3)Mo(2) unit (J(p) = 3.88 cm(
      )(1)). Interunit ferromagnetic interactions (J(c) = -0.03 cm(-)(1)) through a
      longer magnetic pathway of Cu--Mo and weak antiferromagnetic couplings (zJ' = 
      0.46 cm(-)(1)) resulting from interchain interactions are obtained.

PMID- 15500326
TI  - Synthesis of Ru(II) complexes of N-heterocyclic carbenes and their promising
      photoluminescence properties in water.
AB  - Novel complexes 1 and 2 based on N-heterocyclic carbenes, which are analogous to
      Ru(bpy)(3)(2+) and Ru(terpy)(2)(2+), respectively, were synthesized. The complex,
      which is analogous to Ru(terpy)(2)(2+), exhibited promising photoluminescence
      properties with a long lifetime of 820 ns in acetonitrile and 3100 ns in water at
      room temperature, respectively. In addition, ab initio calculations were carried
      out.

PMID- 15500328
TI  - Liberation of pnicogen chains from Cu(2)P(1.8)As(1.2)I(2): synthesis and
      characterization of a new allotrope of P--As.
AB  - Removal of CuI from Cu(2)P(1.8)As(1.2)I(2) results in a novel P--As allotrope.
      Although the product is X-ray amorphous, lattice fringes are observed in the
      transmission electron micrographs with spacings reflecting the diameter of the
      linear pnicogen polymer in Cu(2)P(1.8)As(1.2)I(2), suggesting the pnicogen chains
      remain intact upon loss of CuI. The straight needles present in
      Cu(2)P(1.8)As(1.2)I(2) appear to be kinked in the P--As phase due to lattice
      mismatch between the liberated polymers, ultrasonic treatment, or a combination
      of these effects. This new P--As modification is semiconducting with a band gap
      of 1.05 eV.

PMID- 15500329
TI  - X-ray crystal structures of [XF(6)][Sb(2)F(11)] (X = Cl, Br, I); (35,37)Cl,
      (79,81)Br, and (127)I NMR studies and electronic structure calculations of the
      XF(6)(+) cations.
AB  - The single-crystal X-ray structures of [XF(6)][Sb(2)F(11)] (X = Cl, Br, I) have
      been determined and represent the first detailed crystallographic study of salts
      containing the XF(6)(+) cations. The three salts are isomorphous and crystallize
      in the monoclinic space group P2(1)/n with Z = 4: [ClF(6)][Sb(2)F(11)], a =
      11.824(2) A, b = 8.434(2) A, c = 12.088(2) A, beta = 97.783(6) degrees , V =
      1194.3(4) A(3), R(1) = 0.0488 at -130 degrees C; [BrF(6)][Sb(2)F(11)], a =
      11.931(2) A, b = 8.492(2) A, c = 12.103(2) A, beta = 97.558(4) degrees , V =
      1215.5(4) A(3), R(1) = 0.0707 at -130 degrees C; [IF(6)][Sb(2)F(11)], a =
      11.844(1) A, b = 8.617(1) A, c = 11.979(2) A, beta = 98.915(2) degrees , V =
      1207.8(3) A(3), R(1) = 0.0219 at -173 degrees C. The crystal structure of
      [IF(6)][Sb(2)F(11)] was also determined at -100 degrees C and was found to
      crystallize in the monoclinic space group P2(1)/m with Z = 4, a = 11.885(1) A, b
      = 8.626(1) A, c = 12.000(1) A, beta = 98.44(1), V = 1216.9(2) A(3), R(1) =
      0.0635. The XF(6)(+) cations have octahedral geometries with average Cl-F, Br-F,
      and I-F bond lengths of 1.550(4), 1.666(11) and 1.779(6) [-173 degrees
      C]/1.774(8) [-100 degrees C] A, respectively. The chemical shifts of the central
      quadrupolar nuclei, (35,37)Cl, (79,81)Br, and (127)I, were determined for
      [ClF(6)][AsF(6)] (814 ppm), [BrF(6)][AsF(6)] (2080 ppm), and [IF(6)][Sb(3)F(16)]
      (3381 ppm) in anhydrous HF solution at 27 degrees C, and spin-inversion-recovery
      experiments were used to determine the T(1)-relaxation times of (35)Cl (1.32(3)
      s), (37)Cl (2.58(6) s), (79)Br (24.6(4) ms), (81)Br (35.4(5) ms), and (127)I
      (6.53(1) ms). Trends among the central halogen chemical shifts and T(1)
      relaxation times of XF(6)(+), XO(4)(-), and X(-) are discussed. The isotropic
      (1)J-coupling constants and reduced coupling constants for the XF(6)(+) cations
      and isoelectronic hexafluoro species of rows 3-6 are empirically assessed in
      terms of the relative contributions of the Fermi-contact, spin-dipolar, and spin
      orbit mechanisms. Electronic structure calculations using Hartree-Fock, MP2, and
      local density functional methods were used to determine the energy-minimized gas
      phase geometries, atomic charges, and Mayer bond orders of the XF(6)(+) cations.
      The calculated vibrational frequencies are in accord with the previously
      published assignments and experimental vibrational frequencies of the XF(6)(+)
      cations. Bonding trends within the XF(6)(+) cation series have been discussed in
      terms of natural bond orbital (NBO) analyses, the ligand close-packed (LCP)
      model, and the electron localization function (ELF).

PMID- 15500330
TI  - Local structure and charge distribution in the UO(2)-U(4)O(9) system.
AB  - Analysis of X-ray absorption fine structure spectra of UO(2+x) for x = 0-0.20
      (UO(2)--U(4)O(9)) reveals that the adventitious O atoms are incorporated as oxo
      groups with U--O distances of 1.74 A, most likely associated with U(VI), that
      occur in clusters so that the UO(2) fraction of the material largely remains
      intact. In addition to the formation of some additional longer U--O bonds, the U
      sublattice consists of an ordered portion that displays the original U--U
      distance and a spectroscopically silent, glassy part. This is very different from
      previous models derived from neutron diffraction that maintained long U--O
      distances and high U--O coordination numbers. UO(2+x) also differs from PuO(2+x)
      in its substantially shorter An-oxo distances and no sign of stable coordination
      with H(2)O and its hydrolysis products.

PMID- 15500331
TI  - Binding of inorganic oxoanions to macrocyclic ligands: effect of the degree of
      protonation on supramolecular assemblies formed by phosphate and [18]aneN(6).
AB  - Five macrocycle-oxoanion adducts have been isolated from aqueous solutions
      containing 1,4,7,10,13,16-hexaazacyclooctadecane ([18]aneN(6), L) and phosphoric
      acid whose pH had been adjusted to selected values in the 1-8 range. Four
      products, (H(6)L)(H(2)PO(4))(6).2H(3)PO(4) (1), (H(6)L)(H(2)PO(4))(6) (2),
      (H(4)L)(H(2)PO(4))(4).2H(2)O (4), and (H(4)L)(HPO(4))(2).7H(2)O (5) crystallized
      from aqueous solutions at pH 1, 3, 6, and 8, respectively, while
      (H(4)L)(H(2)PO(4))(4) (3) crystallized on diffusion of EtOH into an aqueous
      reaction mixture at pH 6. Single-crystal X-ray structure determinations enabled
      an examination of supramolecular interactions between protonated forms of
      [18]aneN(6), phosphoric acid and its conjugate bases, and water of solvation. The
      macrocycle adopts a variety of conformations in order to accommodate the
      supramolecular constructs formed by the oxoanions and solvent molecules as the
      relative proportions of interacting species are altered. At pH 1 and 3, the fully
      protonated macrocycle, [LH(6)](6+), is found with six H(2)PO(4)(-) anions. At pH
      6 and 8, the tetraprotonated macrocycle, [LH(4)](4+), crystallizes with four
      H(2)PO(4)(-) and two HPO(4)(2)(-), respectively. Variations in the solute of
      crystallization are evident, with phosphoric acid being present at the lowest pH
      and water at pH 6 and 8. In 5, the seven unique water molecules form a string-of
      pearls motif within which a new heptameric isomer, consisting of a water pentamer
      that uses a single water to interact with the other two unique water molecules,
      is found. Structures 1, 2, 4, and 5 exhibit eta-3 H-bonding of ammonium protons
      to a single oxygen of the guest phosphates located above and below the
      macrocyclic ring. In 3, two phosphate oxygens of the cavity anion interact with
      the macrocycle, one of which participates in eta-2 H-bonding with ammonium
      groups.

PMID- 15500332
TI  - Stepwise synthesis, structures, and reactivity of mono-, di-, and trimetallic
      metal complexes with a 6pi + 6pi quinonoid zwitterion.
AB  - The benzoquinonemonoimine N,N'-dineopentyl-2-amino-5-alcoholate-1,4
      benzoquinonemonoiminium [C(6)H(2)(NHCH(2)t-Bu)(2)(O)(2)] 6, which is a rare
      example of an organic zwitterion being more stable than its canonical form, is
      best described as constituted of two chemically connected but electronically not
      conjugated 6pi electron subunits. The two successive acidities of 6 allow the
      preparation of mono-, di-, and trimetallic complexes in which the control of the
      pi-system delocalization becomes possible. Reaction of 6 with NaOt-Bu results in
      monodeprotonation of one N-H function, and the isolated sodium salt 9, which is
      stable under N(2), reacts with chloride-bridged Pd(II) homodimetallic complexes,
      [AuCl(PPh(3))] or trans-[NiCl(Ph)(PPh(3))(2)], to afford the monometallic
      complexes 10-15 in which the pi-system is localized. A second in situ
      deprotonation of the remaining N-H amino function of 10 with NaH followed by
      reaction with [Pd(8-mq)(mu-Cl)](2) (8-mq = orthometalated 8-methylquinoline)
      affords the homodimetallic complex 17 in which the pi-system of the quinonoid
      ligand is delocalized between the two metal centers. Deprotonation of both N-H
      amino functions of the square-planar complex trans-[Ni(N,O)(2)] 15 with NaH and
      reaction with [Pd(8-mq)(mu-Cl)](2) affords the heterotrimetallic (Pd, Ni, Pd)
      complex 18 in which the pi-system of the two quinonoid ligands is delocalized
      between the three metal centers. The crystal structures of the monometallic
      complexes 10 and 13 and of the dipalladium complex 17 are reported and
      consequences of metal coordination discussed. Complex 15 was tested in catalytic
      ethylene oligomerization with AlEtCl(2) as cocatalyst.

PMID- 15500333
TI  - Reaction products of W(CO)(6) with formamidines; electronic structure of a
      W(2)(mu-CO)(2) core with unsymmetric bridging carbonyls.
AB  - Reactions of W(CO)(6) with formamidines contrast with those of Mo(CO)(6) and
      Cr(CO)(6) in that the former do not yield quadruply bonded dimetal species. From
      the reaction of W(CO)(6) with HDAniF (HDAniF = N,N'-di-p-anisylformamidine),
      several new ditungsten carbonyl compounds (W(2)(mu-CO)(2)(mu-DAniF)(2)(eta(2)
      DAniF)(2) (1), W(2)(mu-CO)(2)(mu-DAniF)(2)(eta(2)-DAniF)(eta(2)-CH(2)DAniF) (2),
      and W(2)(mu-CO)(mu-CNC(6)H(4)OCH(3))(mu-DAniF)(2)(eta(2)-DAniF)(2) (3)) have been
      isolated and fully characterized. In 2, CH(2)DAniF represents a DAniF ligand in
      which a methylene group has been added to one of the nitrogen atoms. This ligand
      binds to the tungsten atom using a nitrogen and a carbon atom. Compound 1 has a
      tungsten-tungsten bond distance of 2.476(1) A and a planar W(2)(mu-CO)(2) core
      structure which has C(2)(h)() symmetry with short and long W-C bond distances
      (1.99(1) and 2.28(1) A, respectively). DFT calculations on a model of 1 indicate
      that (a) the C(2)(h)() instead of D(2)(h)() symmetry of the ditungsten core may
      be attributed to W --> CO pi back-bonding interactions and (b) the bond between
      the tungsten atoms may be formulated as a double bond. The new tetragonal
      paddlewheel compound W(2)(DAniF)(4) (4) and the edge-sharing bioctahedron W(2)(mu
      O)(mu-NC(6)H(3)Cl(2))(mu-D(Cl)PhF)(2)(eta(2)-D(Cl)PhF)(2) (5) (D(Cl)PhF = N,N'-di
      (3,5-dichlorophenyl)formamidinate) have also been prepared.

PMID- 15500334
TI  - Isolation and characterization of a polymeric lanthanum citrate.
AB  - The first lanthanide citrate coordination polymer with the formula
      [La(Hcit)(H(2)O)](n) (Hcit(3-) = C(OH)(COO(-))(CH(2)COO(-))(2)) was prepared from
      La(2)O(3) and citric acid at pH = 2.2-2.5 under hydrothermal conditions at 120
      degrees C. The compound was characterized by elemental analysis, IR, TG-DTA, and
      X-ray crystallography. It is thermally stable up to 158 degrees C and insoluble
      in common solvents. The compound crystallizes in the monoclinic space group C2/c
      with a = 16.765(3) A, b = 8.822(2) A, c = 14.048(3) A, beta = 120.64(3) degrees ,
      and Z = 8. The structure consists of chains of La(III) cations bridged by O--C--O
      groups with pendant Hcit anions forming a pillar structure. The Hcit ligand is
      involved in six La--O bonds to five different La centers in a very compact 3D
      structure.

PMID- 15500335
TI  - Electrochemical, spectral, and computational studies of metalloporphyrin dimers
      formed by cation complexation of crown ether cavities.
AB  - The effect on the electrochemical oxidation and reduction potentials of
      5,10,15,20-tetrakis(benzo-15-crown-5)porphyrin (TCP) and its metal derivatives
      (MTCP; M = Mg(II), VO(IV), Co(II), Ni(II), Cu(II), Zn(II), Pd(II), Ag(II)) upon
      potassium ion induced dimerization of the porphyrins was systematically performed
      in benzonitrile containing 0.1 M (TBA)ClO(4) by differential pulse voltammetry
      technique. The HOMO--LUMO energy level diagram constructed from the
      electrochemical data revealed destabilization of the HOMO level and stabilization
      of the LUMO level upon dimer formation while such a perturbation was larger for
      the HOMO level than the LUMO level. The geometry and electronic structure of a
      representative ZnTCP and its dimer, K(4)(ZnTCP)(2), were evaluated by the ab
      initio B3LYP method utilizing a mixed basis set of 3-21G(*) for Zn, K, O, and N
      and STO-3G for C and H. The inter-porphyrin ring distance of the dimer calculated
      from the optimized geometry agreed with the spectroscopically determined one, and
      the calculated HOMO and LUMO frontier orbitals revealed delocalization on both of
      the porphyrins rings. The metal-metal distances calculated from the triplet ESR
      spectra of the K(+) induced porphyrin dimers bearing paramagnetic metal ions in
      the cavity followed the trend Cu--Cu < VO--VO < Ag--Ag. However, the spectral
      shifts resulting from the exciton coupling of the interacting porphyrin pi
      systems revealed no specific trend with respect to the metal ion in the porphyrin
      cavity. Additionally, linear trends in the electrochemically measured HOMO--LUMO
      gap and the energy corresponding to the most intense visible band of both MTCP
      and K(4)(MTCP)(2) were observed. A reduced HOMO--LUMO gap predicted for the dimer
      by B3LYP/(3-21G(), STO-3G) calculations was confirmed by the results of optical
      absorption and electrochemical studies.

PMID- 15500336
TI  - Spectroscopic properties and electronic structure of pentammineruthenium(II)
      dinitrogen oxide and corresponding nitrosyl complexes: binding mode of N(2)O and
      reactivity.
AB  - The spectroscopic properties and the electronic structure of the only nitrous
      oxide complex existing in isolated form, [Ru(NH(3))(5)(N(2)O)]X(2) (1, X = Br(-),
      BF(4)(-)), are investigated in detail in comparison to the nitric oxide
      precursor, [Ru(NH(3))(5)(NO)]X(3) (2). IR and Raman spectra of 1 and of the
      corresponding (15)NNO labeled complex are presented and assigned with the help of
      normal coordinate analysis (NCA) and density functional (DFT) calculations. This
      allows for the identification of the Ru-N(2)O stretch at approximately 300 cm(
      )(1) and for the unambiguous definition of the binding mode of the N(2)O ligand
      as N-terminal. Obtained force constants are 17.3, 9.6, and 1.4 mdyn/A for N-N, N
      O, and Ru-N(2)O, respectively. The Ru(II)-N(2)O bond is dominated by pi back
      donation, which, however, is weak compared to the NO complex. This bond is
      further weakened by Coulomb repulsion between the fully occupied t(2g) shell of
      Ru(II) and the HOMO of N(2)O. Hence, nitrous oxide is an extremely weak ligand to
      Ru(II). Calculated free energies and formation constants for
      [Ru(NH(3))(5)(L)](2+) (L = NNO, N(2), OH(2)) are in good agreement with
      experiment. The observed intense absorption at 238 nm of 1 is assigned to the
      t(2g) --> pi(*) charge transfer transition. These data are compared in detail to
      the spectroscopic and electronic structural properties of NO complex 2. Finally,
      the transition metal centered reaction of nitrous oxide to N(2) and H(2)O is
      investigated. Nitrous oxide is activated by back-donation. Initial protonation
      leads to a weakening of the N-O bond and triggers electron transfer from the
      metal to the NN-OH ligand through the pi system. The implications of this
      mechanism for biological nitrous oxide reduction are discussed.

PMID- 15500337
TI  - Titanatranes derailed: static and dynamic triethanolamine slippage induced by
      polyphenoxide chelation.
AB  - Aryloxytitanatranes [N(CH(2)CH(2)O)(3)]Ti[OC(6)H(2)-2,4-(t)()Bu(2)-6-CHPh(3)(
      )(n)()(C(6)H(2)-3,5-(t)()Bu(2)-2-OH)(n)(-)(1)] (1, n = 1; 2, n = 2; 3, n = 3)
      containing aryloxides derived from substituted triphenylmethanes are formed in
      high yield in the reactions of the corresponding phenols with tert
      butoxytitanatrane [N(CH(2)CH(2)O)(3)]Ti(O(t)()Bu). The aryloxytitanatranes adopt
      monomeric, trigonal bipyramidal structures, as confirmed by X-ray crystallography
      for 1 and 2. The compounds with pendant phenol groups display fluxional behavior
      due to interchange of the bound phenoxide with the free phenol groups, most
      likely via a mechanism involving displacement of one arm of the
      nitrilotriethoxide by the dangling phenol group. The amidotitanatrane
      [[N(CH(2)CH(2)O)(3)]Ti(NEt(2))](2) reacts with the bisphenol PhCH(C(6)H(2)-3,5
      (t)()Bu(2)-2-OH)(2) to give a crystallographically characterized fully metalated
      cyclic octatitanium complex of the formula [PhCH(C(6)H(2)-3,5-(t)()Bu(2)-2
      O)(2)Ti(2)[(OCH(2)CH(2))(3)N](2)](4) (4). The structure of 4 reveals a
      metallamacrocycle (minimum ring size = 28 members) consisting of four repeating
      unsymmetrical dititanium units. In each dititanium unit, there is an
      unprecedented slippage of the nitrilotriethoxide ligand such that both
      triethanolamine nitrogens coordinate to only one of the two titaniums, while the
      bisphenoxide is coordinated only to the other titanium. The propensity of the
      polyphenoxide ligands to chelate is attributed to favorable pi-bonding
      interactions attainable in the eight-membered chelate rings.

PMID- 15500338
TI  - A europium-151 Mossbauer spectral study of Eu(14)MnP(11), Eu(14)MnAs(11), and
      Eu(14)MnSb(11).
AB  - The europium-151 Mossbauer spectra of the Eu(14)MnP(11), Eu(14)MnAs(11), and
      Eu(14)MnSb(11) Zintl compounds, measured between 4.2 and 100 K, reveal
      europium(II) for all four crystallographically inequivalent europium sites in
      Eu(14)MnAs(11) and Eu(14)MnSb(11) and europium(II) and europium(III) for the
      three 32g and the 16f europium sites in Eu(14)MnP(11), respectively. Below the
      ordering temperatures of 52, 74, and 92 K, only very small hyperfine fields of 2
      4 T are observed at the europium sites as a result of the polarization by the
      manganese magnetic moments. At 4.2 K, the europium(II) magnetic moments are
      ordered, and hyperfine fields of 24.4, 24.8, and 19.3 T are observed in
      Eu(14)MnP(11), Eu(14)MnAs(11), and Eu(14)MnSb(11), respectively, fields that are
      typical for magnetically ordered europium(II) ions. At 4.2 K the 16f
      europium(III) sites in Eu(14)MnP(11) experience a transferred hyperfine field of
      33 T from the neighboring ordered europium(II) moments. Between its Curie
      temperature and 4.2 K, the europium-151 Mossbauer spectra of Eu(14)MnSb(11)
      reveal that the europium(II) moments order below ca. 13 K, i.e., below the second
      magnetic transition observed in magnetic measurements. Between their Curie
      temperatures and 4.2 K, the europium-151 Mossbauer spectra of Eu(14)MnP(11) and
      Eu(14)MnAs(11) are complex and have been analyzed with two models, models that
      give equivalently good fits. However, the second model in which the spectra are
      fit with a three-dimensional relaxation of the europium(II) and europium(III)
      hyperfine fields is preferred for its physical meaning and its reduced number of
      fitted parameters.

PMID- 15500339
TI  - Solid-state coordination chemistry of the oxomolybdate-organodiphosphonate/nickel
      organoimine system: structural influences of the secondary metal coordination
      cation and diphosphonate tether lengths.
AB  - The hydrothermal reactions of a molybdate source, a nickel(II) salt, tetra-2
      pyridylpyrazine (tpyprz), and organodiphosphonic acids
      H(2)O(3)P(CH(2))(n)()PO(3)H(2) (n = 1-5) of varying tether lengths yielded a
      series of organic-inorganic hybrid materials of the nickel-molybdophosphonate
      family. A persistent characteristic of the structural chemistry is the presence
      of the [Mo(5)O(15)(O(3)PR)(2)](4)(-) cluster as a molecular building block, as
      noted for the one-dimensional materials
      [[Ni(2)(tpyprz)(2)]Mo(5)O(15)[O(3)P(CH(2))(4)PO(3)]]x6.65H(2)O (6x6.65H(2)O) and
      [[Ni(2)(tpyprz)(2)]Mo(5)O(15)[O(3)P(CH(2))(5)PO(3)]]x3.75H(2)O (8x3.75H(2)O), the
      two-dimensional phases
      [[Ni(4)(tpyprz)(3)][Mo(5)O(15)(O(3)PCH(2)CH(2)PO(3))](2)]x23H(2)O (3x23H(2)O) and
      [[Ni(3)(tpyprz)(2)(H(2)O)(2)](Mo(5)O(15))(Mo(2)O(4)F(2))[O(3)P(CH(2))(3)PO(3)](2)
      x8H(2)O (5x8H(2)O), and the three-dimensional structures
      [[Ni(2)(tpyprz)(H(2)O)(3)]Mo(5)O(15)[O(3)P(CH(2))(3)PO(3))]]xH(2)O (4xH(2)O) and
      [[Ni(2)(tpyprz)(H(2)O)(2)]Mo(5)O(15) [O(3)P(CH(2))(4)PO(3)]]x2.25H(2)O
      (7x2.25H(2)O). In the case of methylenediphosphonic acid, the inability of this
      ligand to tether adjacent pentanuclear clusters precludes the formation of the
      common molybdophosphonate building block, manifesting in contrast a second
      structural motif, the trinuclear [(Mo(3)O(8))(x)(O(3)PCH(2)PO(3))(y)] subunit of
      [[Ni(tpyprz)(H(2)O)(2)](Mo(3)O(8))(2) (O(3)PCH(2)PO(3))(2)] (1) which had been
      previously observed in the corresponding methylenediphosphonate phases of the
      copper-molybdophosphonate family. Methylenediphosphonic acid also provides a
      second phase, [Ni(2)(tpyprz)(2)][Mo(7)O(21)(O(3)PCH(2)PO(3))]x3.5H(2)O
      (9x5H(2)O), which contains a new heptamolybdate cluster
      [Mo(7)O(21)(O(3)PCH(2)PO(3))](4)(-) and a cationic linear chain
      [Ni(tpyprz)](n)(4n+) substructure. The structural chemistry of the nickel
      molybdophosphonate series contrasts with that of the corresponding copper
      molybdophosphonate materials, reflecting in general the different coordination
      preferences of Ni(II) and Cu(II). Consequently, while the Cu(II)-organic complex
      building block of the copper family is invariably the binuclear
      [Cu(2)(tpyprz)](4+) subunit, the Ni(II) chemistry with tpyprz exhibits a distinct
      tendency toward catenation to provide [Ni(3)(tpyprz)(2)](6+),
      [Ni(4)(tpyprz)(3)](8+), and [Ni(tpyprz)](n)(4n+) building blocks as well as the
      common [Ni(2)(tpyprz)](4+) moiety. This results in a distinct structural
      chemistry for the nickel(II)-molybdophosphonate series with the exception of the
      methylenediphosphonate derivative 1 which is isostructural with the corresponding
      copper compound [[Cu(2)(tpyprz)(H(2)O)(2)](Mo(3)O(8))(2)(O(3)PCH(2)PO(3))] (2).
      The structural chemistry of the nickel(II) series also reflects variability in
      the number of attachment sites at the molybdophosphonate clusters, in the extent
      of aqua ligation to the Ni(II) tpyprz subunit, and in the participation of
      phosphate oxygen atoms as well as molybdate oxo groups in linking to the nickel
      sites.

PMID- 15500340
TI  - Theoretical investigations of the electronic structure and spectroscopy of
      mononuclear, non-heme [Fe-NO](6) complexes.
AB  - The unusual metal coordination and spin-state of the Fe(III) center in nitrile
      hydratase (NHase) has stimulated the synthesis of numerous model complexes in
      efforts to understand the reactivity and spectroscopic properties of the enzyme.
      A particular problem has been the development of model Fe(III) complexes that
      exhibit reversible, photolabile binding to nitric oxide (NO) in a manner similar
      to that observed for the NHase metal center. We now report a detailed NBO
      analysis of the ground-state chemical bonding in three [Fe-NO](6) complexes that
      exhibit different responses to irradiation, together with investigations of their
      spectroscopic properties using semiempirical INDO/S CI singles calculations. Our
      computational studies reveal a correlation between the photolability of these
      complexes and the existence of low-energy transitions that promote an electron
      into the Fe-NO pi(*) antibonding molecular orbital. In addition to providing
      detailed insights into how the ligand field influences the spectroscopy of these
      mononuclear complexes, these studies strengthen our previous conclusions
      regarding the role of post-translational cysteine modification in modulating the
      photoreactivity of the inactive, NO complex of NHase.

PMID- 15500341
TI  - Preparation and characterization of novel inorganic-organic hybrid materials
      containing rare, mixed-halide anions of bismuth(III).
AB  - Three new hybrid inorganic-organic salts containing novel mixed haloanions of
      bismuth were synthesized by the solvothermal reaction of bismuth iodide with a
      haloacid, HX (X = Cl or Br), and the alkylamine 4,4'-trimethylenedipiperidine
      (TMDP). All three compounds were structurally characterized by single-crystal X
      ray diffraction. Reaction of TMDP and BiI(3) with HCl yielded two crystalline
      products: [H(2)TMDP](2)[(Bi(2)I(9))(BiCl(2)I(2))] (1, major yield) and
      [H(2)TMDP](2)[Bi(2)Cl(10-x)I(x)] (2, x = 3.83, minor yield). Compound 1
      crystallizes in the monoclinic space group Cc (a = 22.8586(11) A, b = 15.5878(7)
      A, c = 17.6793(9) A, beta = 118.7010(10) degrees , Z = 4) and contains the
      mononuclear mixed-halide anion BiCl(2)I(2)(-) in addition to a face-sharing
      bioctahedral Bi(2)I(9)(3)(-) anion and two independent H(2)TMDP(2+) cations. The
      BiCl(2)I(2)(-) anion has a sawhorse geometry (equatorially vacant trigonal
      bipyramidal geometry) that is not commonly observed in bismuth chemistry.
      Compound 2 crystallizes in the monoclinic space group P2(1)/c (a = 14.9471(7) A,
      b = 12.7622(6) A, c = 13.3381(7) A, beta = 116.1030(10) degrees , Z = 2) and
      contains an edge-sharing bioctahedral mixed-halide anion in which iodide occupies
      one and chloride occupies two of the five crystallographically independent halide
      sites. The remaining two sites have mixed-chloride and -iodide occupancy.
      Reaction of TMDP and BiI(3) with HBr yielded the crystalline product
      [H(2)TMDP][BiBr(5-x)I(x)] (3, x = 0.99), which contains, in addition to the
      organic cation, a polymeric, mixed-haloanion of bismuth(III). Compound 3
      crystallizes in the chiral, orthorhombic space group P2(1)2(1)2(1) (a = 8.5189(5)
      A, b = 14.8988(9) A, c = 17.9984(11) A, Z = 4) and consists of an H(2)TMDP(2+)
      cation in addition to the anion, which is built up of corner-sharing BiX(6)
      octahedra. Of the five crystallographically independent halide sites in this
      anion, two are occupied solely by Br and the remaining three have mixed-bromide
      and -iodide occupancy. Other anion stoichiometries have been observed
      crystallographically for 3, as the specific stoichiometry is dependent on the
      relative concentration of the haloacid starting material used.

PMID- 15500342
TI  - Antifluorite-type lithium chromium oxide nitrides: synthesis, structure, order,
      and electrochemical properties.
AB  - Antifluorite-type lithium chromium oxide nitrides were prepared by solid-state
      reaction of Li(3)N, Li(2)O, and Cr(2)N. Depending on the reaction time and
      starting Li/Cr and O/Cr ratios, either an ordered or a disordered phase (or
      mixtures of both) is obtained. The formation of the former is favored by short
      reaction times and low Cr/O ratios whereas the formation of the latter is favored
      by higher Cr/O ratios and longer reaction times. The two phases were
      characterized, and the first one was confirmed to be the already reported
      Li(14)Cr(2)N(8)O phase, whereas the stoichiometry of the second is
      Li(10)CrN(4)O(2). Interestingly, even if both contain cationic vacancies in the
      structure, electrochemical lithium intercalation could only be achieved for
      Li(10)CrN(4)O(2). This phase exhibits a reversible capacity of 160 mAh/g very
      stable upon cycling. Bond valence and first-principles DFT calculations were
      carried out to understand the absence of lithium insertion in Li(14)Cr(2)N(8)O.
      Li-Li repulsion and destabilization of the tetrahedral CrN(4) units induced by
      occupation of the potential sites, as well as the absence of energetically
      favorable pathways for transport of the ions to these sites, are suggested to be
      the reasons.

PMID- 15500343
TI  - Electronic interaction in an outer-sphere mixed-valence double salt: a polarized
      neutron diffraction study of K(3)(MnO(4))(2).
AB  - The mixed-valence double salt K(3)(MnO(4))(2) crystallizes in space group P2(1)/m
      with Z = 2. The manganese centers Mn1 and Mn2 constitute discrete "permanganate",
      [Mn(VII)O(4)](-), and "manganate", [Mn(VI)O(4)](2-), ions, respectively. There is
      a spin-ordering transition to an antiferromagnetic state at ca. T = 5 K. The spin
      density distribution in the paramagnetic phase at T = 10 K has been determined by
      polarized neutron diffraction, confirming that unpaired spin is largely confined
      to the nominal manganate ion Mn2. Through use of both Fourier refinement and
      maximum entropy methods, the spin on Mn1 is estimated as 1.75 +/- 1% of one
      unpaired electron with an upper limit of 2.5%.

PMID- 15500344
TI  - Rhenium(V) oxo complexes with N-heterocyclic carbenes.
AB  - Air-stable rhenium(V) oxo complexes are formed when [ReOCl(3)(PPh(3))(2)] is
      treated with N-heterocyclic carbenes of the 1,3-dialkyl-4,5-dimethylimidazol-2
      ylidene type, L(R) (R = Me, Et, i-Pr). Complexes of the compositions
      [ReO(2)(L(R))(4)](+), [ReOCl(L(R))(4)](2+), or [ReO(OMe)(L(R))(4)](2+) can be
      isolated depending on the alkyl substituents at the nitrogen atoms of the ligands
      and the reaction conditions applied. Despite the steric overcrowding of the
      equatorial coordination spheres of the metal atoms by each of the four carbene
      ligands, stable complexes with six-coordinate rhenium atoms are obtained. Steric
      demands of the alkyl groups allow control of the stability of the mono-oxo
      intermediates. Air-stable cationic complexes of the compositions
      [ReOCl(L(Me))(4)](2+), [ReOCl(L(Et))(4)](2+), and [ReO(OMe)(L(Me))(4)](2+) have
      been isolated, whereas reactions of [ReOCl(3)(PPh(3))(2)] or other rhenium(V)
      precursors with the more bulky 1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene
      (L(i)(-)(Pr)) directly yield the dioxo complex [ReO(2)(L(i)(-)(Pr))(4)](+). X-ray
      structures of [ReO(2)(L(i)(-)(Pr))(4)][ReO(4)], [ReO(2)(L(i)(-)(Pr))(4)][PF(6)],
      [ReO(2)(L(Me))(4)][ReO(4)](0.45)[PF(6)](0.55), [ReO(MeOH)(L(Me))(4)][PF(6)](2),
      and [ReOCl(L(Et))(4)][PF(6)](2) show that the equatorial coordination spheres of
      the rhenium atoms are essentially planar irrespective of the steric demands of
      the individual carbene ligands.

PMID- 15500345
TI  - Supramolecular copper hydroxide tennis balls: self-assembly, structures, and
      magnetic properties of octanuclear [Cu(8)L(8)(OH)(4)](4+) clusters (HL = N-(2
      pyridylmethyl)acetamide).
AB  - The self-assembly of supramolecular copper "tennis balls" that possess unusual
      magnetic properties using a small pyridyl amide ligand is described. Copper(II)
      complexes of N-(2-pyridylmethyl)acetamide (HL) were synthesized in methanol. In
      the absence of base, the mononuclear complex [Cu(HL)(2)](ClO(4))(2) (1) was
      prepared. The structure of 1, determined by X-ray crystallography, contains a
      copper(II) ion surrounded by bidentate HL ligands coordinated via the pyridyl N
      atom and the carbonyl O atom in a trans, square planar arrangement. Reactions
      carried out in the presence of triethylamine resulted in cluster complexes
      [Cu(8)L(8)(OH)(4)](ClO(4))(4) and [Cu(8)L(8)(OH)(4)](CF(3)SO(3))(4) [2(ClO(4))(4)
      and 2(OTf)(4), respectively]. The cationic portions of 2(ClO(4))(4) and 2(OTf)(4)
      are isostructural, containing eight copper(II) ions, eight deprotonated ligands
      (L(-)), and four mu(3)-hydroxide ligands. The top and bottom halves of the
      cluster are related by a pseudo-S(4) symmetry operation and are held together by
      bridging L(-) ligands. Solutions of 2(ClO(4))(4) and 2(OTf)(4), which were shown
      to contain the full [Cu(8)L(8)(OH)(4)](4+) fragment by electrospray mass
      spectrometry and conductance experiments, are EPR silent. Magnetic susceptibility
      measurements for 2(ClO(4))(4) as a function of temperature and magnetic field
      showed the Cu ions all to exhibit magnetic moments in the range expected for the
      d(9) configuration. At low temperatures, the magnetization was reduced due to
      predominantly antiferromagnetic interactions between ions. Analysis showed that
      partially frustrated interactions among the four Cu ions making up each half of
      the cluster gave good agreement with the data once a large molecular anisotropy
      was taken into account, with J(c) = 106 cm(-1), D = 27 cm(-1), and g = 2.17.

PMID- 15500346
TI  - Tuning of redox potentials for the design of ruthenium anticancer drugs -- an
      electrochemical study of [trans-RuCl(4)L(DMSO)](-) and [trans-RuCl(4)L(2)](-)
      complexes, where L = imidazole, 1,2,4-triazole, indazole.
AB  - The electrochemical behavior of [trans-RuCl(4)L(DMSO)](-) (A) and [trans
      RuCl(4)L(2)](-) (B) [L = imidazole (Him), 1,2,4-triazole (Htrz), and indazole
      (Hind)] complexes has been studied in DMF, DMSO, and aqueous media by cyclic
      voltammetry and controlled potential electrolysis. They exhibit one single
      electron Ru(III)/Ru(II) reduction involving, at a sufficiently long time scale,
      metal dechlorination on solvolysis, as well as, in organic media, one single
      electron reversible Ru(III)/Ru(IV) oxidation. The redox potential values are
      interpreted on the basis of the Lever's parametrization method, and particular
      forms of this linear expression (that relates the redox potential with the ligand
      E(L) parameter) are proposed, for the first time, for negatively (1-) charged
      complexes with the Ru(III/II) redox couple center in aqueous phosphate buffer (pH
      7) medium and for complexes with the Ru(III/IV) couple in organic media. The E(L)
      parameter was estimated for indazole showing that this ligand behaves as a weaker
      net electron donor than imidazole or triazole. The kinetics of the reductively
      induced stepwise replacement of chloride by DMF were studied by digital
      simulation of the cyclic voltammograms, and the obtained rate constants were
      shown to increase with the net electron donor character (decrease of E(L)) of the
      neutral ligands (DMSO < indazole < triazole < imidazole) and with the basicity of
      the ligated azole, factors that destabilize the Ru(II) relative to the Ru(III)
      form of the complexes. The synthesis and characterization of some novel complexes
      of the A and B series are also reported, including the X-ray structural analyses
      of (Ph(3)PCH(2)Ph)[trans-RuCl(4)(Htrz)(DMSO)], [(Ph(3)P)(2)N][trans
      RuCl(4)(Htrz)(DMSO)], (H(2)ind)[trans-RuCl(4)(Hind)(DMSO)], and
      [(Hind)(2)H][trans-RuCl(4)(Hind)(2)].

PMID- 15500347
TI  - Stabilization of a subvalent oxidation state of bismuth in N,N
      dimethylthioformamide solution: an EXAFS, UV-Vis, IR, and cyclic voltammetry
      study.
AB  - At the dissolution of anhydrous bismuth(III) trifluoromethanesulfonate in N,N
      dimethylthioformamide (DMTF) a deep red-orange complex, lambda(max) = 457 nm, is
      formed. Bismuth(III) is reduced by the solvent to a low-valent oxidation state
      stabilized by the sulfur-coordinating solvent DMTF. The obtained complex is
      weakly solvated seen by a low EXAFS amplitude and a slightly higher absorption
      energy of the L(III) edge than of the DMTF-solvated bismuth(III) ion. The EXAFS
      data reveal a dimeric bismuth complex solvated by a single DMTF molecule, which
      sulfur atom bridges the bismuth atoms. The Bi-S bond distance is 2.543(2) A, and
      the Bi...Bi distance is 3.929(7) A giving a Bi-S-Bi angle of 101.2(4) degrees.
      The very low number of coordinated solvent molecule shows that the lone electron
      pairs of the reduced bismuth ions are stereochemically active. Cyclic voltammetry
      investigations provide evidence that at least one bismuth atom in the dimer
      exists in an oxidation state lower than +III, seen by two peaks at approximately 
      0.36 and -0.57 V in the reduction half-cycle. The absence of EPR signals excludes
      the presence of bismuth(II) radicals.

PMID- 15500348
TI  - Synthesis and properties of palladium diselenolenes: X-ray crystal structures of
      [Pd[SeC(R(1))=C(R(2))Se](PBu(3))(2)] [R(1), R(2) = (CH(2))(n), n = 4, 5, 6].
AB  - The reaction between [Pd(2)(dba)(3)] (dba = dibenzylideneacetone),
      tributylphosphine, and a bis(cycloalkeno)-1,4-diselenin leads to either a
      mononuclear diselenolene [Pd[SeC(R(1))=C(R(2))Se](PBu(3))(2)] or a dinuclear
      diselenolene [Pd(2)[SeC(R(1))=C(R(2))Se](2)(PBu(3))(2)] [R(1), R(2) = (CH(2))(n),
      n = 4, 5, 6] depending on the stoichiometry employed. Treatment of the dinuclear
      diselenolenes with 1,2-bis(diphenylphosphino)ethane (dppe) provides a high
      yielding route to the mononuclear species [Pd[SeC(R(1))=C(R(2))Se](dppe)]. All
      new compounds have been characterized by standard spectroscopic and analytical
      techniques, in particular by multinuclear NMR spectroscopy; the structure of each
      of the mononuclear tributylphosphine complexes has been determined by X-ray
      crystallography. Computational studies show that the observed asymmetry of the
      diselenolenes in the solid state is a result primarily of intramolecular
      repulsive interactions between the ligands.

PMID- 15500349
TI  - Zirconium, hafnium, and tantalum amide silyl complexes: their preparation and
      conversion to metallaheterocyclic complexes via gamma-hydrogen abstraction by
      silyl ligands.
AB  - New transition metal silyl amide complexes
      (Me(2)N)(3)Ta[N(SiMe(3))(2)](SiPh(2)Bu(t)) (1) and
      (Me(2)N)M[N(SiMe(3))(2)](2)(SiPh(2)Bu(t)) (M = Zr, 2a, and Hf, 2b) were found to
      undergo gamma-H abstraction by the silyl ligands to give metallaheterocyclic
      complexes (3) and (M = Zr, 4a, and Hf, 4b), respectively. The conversion of 1 to
      3 follows first-order kinetics with DeltaH() = 23.6(1.6) kcal/mol and DeltaS() =
      3(5) eu between 288 and 313 K. The formation of 4a from
      (Me(2)N)Zr[N(SiMe(3))(2)](2)Cl (5a) and Li(THF)(2)SiPh(2)Bu(t) (6) involves the
      formation of the intermediate 2a, followed by gamma-H abstraction. Kinetic
      studies of these consecutive reactions, a second-order reaction to give 2a and
      then a first-order gamma-H abstraction to give 4a, were conducted by an
      analytical method and a numerical method. At 278 K, the rate constants k(1) and
      k(2) for the two consecutive reactions are 2.17(0.03) x 10(-)(3) M(-)(1) s(-)(1)
      and 5.80(0.15) x 10(-)(5) s(-)(1) by the analytical method. The current work is a
      rare kinetic study of the A + B --> C --> D (+ E) consecutive reactions. Kinetic
      studies of the formation of a metallaheterocyclic moiety have, to our knowledge,
      not been reported. In addition, gamma-H abstraction by a silyl ligand to give
      such a metallaheterocyclic moiety is new. Theoretical investigations of the gamma
      H abstraction by silyl ligands have been conducted by density functional theory
      calculations at the Becke3LYP (B3LYP) level, and they revealed that the formation
      of the metallacyclic complexes through gamma-H abstraction is entropically
      driven. X-ray crystal structures of (Me(2)N)(3)Ta[N(SiMe(3))(2)](SiPh(2)Bu(t))
      (1), (Me(2)N)Zr[N(SiMe(3))(2)](2)Cl (5a), and (M = Zr, 4a, and Hf, 4b) are also
      reported.

PMID- 15500350
TI  - Synthesis and characterization of heavier dioxouranium(VI) dihalides.
AB  - The synthesis and characterization of the dioxouranium(VI) dibromide and iodide
      hydrates, UO(2)Br(2)x3H(2)O (1), [UO(2)Br(2)(OH(2))(2)](2) (2), and
      UO(2)I(2)x2H(2)Ox4Et(2)O (3), are reported. Moreover, adducts of UO(2)I(2) and
      UO(2)Br(2) with large, bulky OP(NMe(2))(3) and OPPh(3) ligands such as
      UO(2)I(2)(OP(NMe(2))(3))(2) (4), UO(2)Br(2)(OP(NMe(2))(3))(2) (5), and
      UO(2)I(2)(OPPh(3))(2)(6) are discussed. The structures of the following compounds
      were determined using single-crystal X-ray diffraction techniques: (1)
      monoclinic, P2(1)/c, a = 9.7376(8) A, b = 6.5471(5) A, c = 12.817(1) A, beta =
      94.104(1) degrees , V = 815.0(1) A(3), Z = 4; (2) monoclinic, P2(1)/c, a =
      6.0568(7) A, b = 10.5117(9) A, c = 10.362(1) A, beta = 99.62(1) degrees , V =
      650.5(1) A(3), Z = 2; (4) tetragonal, P4(1)2(1)2, a = 10.6519(3) A, b =
      10.6519(3) A, c = 24.0758(6) A, V = 2731.7(1) A(3), Z = 4; (5) tetragonal,
      P4(1)2(1)2, a = 10.4645(1) A, b = 10.4645(1) A, c = 23.7805(3) A, V = 2604.10(5)
      A(3), Z = 4, and (6) monoclinic, P2(1)/c, a = 9.6543(1) A, b = 18.8968(3) A, c =
      10.9042(2) A, beta =115.2134(5) degrees , V = 1783.01(5) A(3), Z = 2. Whereas 1
      and 2 are the first UO(2)Br(2) hydrates and the last missing members of the
      UO(2)X(2) hydrate (X = Cl --> I) series to be structurally characterized, 4 and 6
      contain room-temperature stable U(VI)-I bonds with 4 being the first structurally
      characterized room temperature stable U(VI)-I compound which can be conveniently
      prepared on a gram scale in quantitative yield. The synthesis and
      characterization of 5 using an analogous halogen exchange reaction to that used
      for the preparation of 4 is also reported.

PMID- 15500351
TI  - Mononuclear and dinuclear monoperoxovanadium(v) complexes with a hetero ligand.
      1.(1) Self-decomposition reaction, detection of reactive oxygen species, and
      oxidizing ability.
AB  - A mononuclear peroxovanadium(V) complex with histamine-N,N-diacetate (histada),
      K[VO(O(2))(histada)], and a dinuclear peroxovanadium(V) complex with 2-oxo-1,3
      diaminopropane-N,N,N',N'-tetraacetate (dpot), Cs(3)[(VO)(2)(O(2))(2)(dpot)], were
      prepared and characterized. The self-decomposition reaction was examined for
      these peroxovanadium(V) complexes as well as for K[VO(O(2))(cmhist)] (cmhist = N
      carboxymethylhistidinate). The reaction profiles depicted by the absorbance
      change in the UV-vis spectrum show a sigmoid shape with an induction period. The
      induction period is reduced by the addition of acid, fluoride, thiocyanate,
      VO(2+), VO(2)(+), and trolox compared to the solution containing perchlorate. On
      the other hand, the induction period was elongated by the addition of chloride,
      bromide, and 2-tert-butyl-p-cresol. These behaviors are discussed on the basis of
      a radical chain mechanism. The self-decomposition reactions have also been
      followed by the (1)H and (51)V NMR and EPR spectra. These spectral studies as
      well as the UV-vis spectral study indicate that vanadium(V) is partly reduced to
      vanadium(IV) in the self-decomposition process. The histada complex yields a
      mixed-valence dinuclear complex in a concentrated solution, and the dpot complex
      yields a mixed-valence tetranuclear complex. The reduction of vanadium ion
      suggests that the peroxo ligand may act as a reducing agent. In order to know the
      fate of the peroxo ligand, we tried to detect superoxide anion and hydroxyl
      radical, which were anticipated to be produced in the self-decomposition process.
      The formation of superoxide anion was spectrophotometrically confirmed using two
      independent methods, including the reduction of cytochrome c and the reduction of
      sodium 4-[3-(iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene
      disulfonate (WST-1). The formation of hydroxyl radical was confirmed by an EPR
      spin trapping technique. The oxidizing abilities of the peroxovanadium(V)
      complexes toward bovine serum albumin (BSA) were also evaluated. In the protein
      carbonyl assay, it was found that the total amount of protein carbonyl in BSA was
      increased by the reaction with the peroxovanadium complexes in the concentration
      dependent manner. In addition, the oxidation of sulfhydryl group in BSA induced
      by the peroxovanadium complexes was confirmed.

PMID- 15500352
TI  - Cation mobility and kinetics of ion exchange in zirconium hydrogen
      monothiophosphate hydrate, Zr(HPO(3)S)(2)x1.5H(2)O.
AB  - The ion conductivity of zirconium hydrogen monothiophosphate
      (Zr(HPO(3)S)(2)x1.5H(2)O) has been measured by impedance spectroscopy. The
      measured value of proton conductivity is 3 x 10(-5) S/cm at 298 K. Conductivity
      was shown to decrease with increasing temperature due to a dehydration process.
      Above 450 K, the conductivity is likely governed by proton transport in the
      anhydrous phase Zr(HPO(3)S)(2). The activation energies of proton conductivity
      were measured to be 18 +/- 2 kJ/mol for Zr(HPO(3)S)(2)x1.5H(2)O and 60 +/- 3
      kJ/mol for the anhydrous compound. The kinetics of ion exchange was studied with
      the use of potentiometric titration for several ion pairs, H(+)/Na(+),
      H(+)/Zn(2+), and Na(+)/Zn(2+) in Zr(HPO(3)S)(2)x1.5H(2)O. The diffusion
      coefficient values for H(+)/Na(+) ion exchange in Zr(HPO(3)S)(2)x1.5H(2)O are
      lower than those reported in alpha-zirconium phosphate. At the same time, the
      mobility of zinc ions in Zr(HPO(3)S)(2)x1.5H(2)O is higher than sodium ion
      mobility. The ion exchange H(+)/Zn(2+) is accompanied by the slow hydrolysis of
      the initial compound. In all cases, the powdered solids were evaluated by powder
      X-ray diffraction, and particle sizes were controlled by grinding and sieving the
      powders.

PMID- 15500353
TI  - Solid mercury dihydride: mercurophilic bonding in molecular HgH(2) polymers.
AB  - Atomic mercury subjected to mercury arc irradiation reacts in solid hydrogen to
      give the linear HgH(2) molecule with strong IR absorptions at 1902 and 773 cm(
      1). Annealing leads to HgH(2) dimer and trimer, and warming above 7 K allows the
      hydrogen matrix to sublime and solid HgH(2) to form. This covalent molecular
      solid is characterized by strong IR absorptions at 1802 and 673 cm(-1) and by
      decomposition at 150-170 K.

PMID- 15500354
TI  - Effects of peripheral substituents and axial ligands on the electronic structure
      and properties of iron phthalocyanine.
AB  - The effects of peripheral substituents and axial ligands on the electronic
      structure and properties of iron phthalocyanine, H(16)PcFe, have been
      investigated using a DFT method. Substitution by electron-withdrawing fluorinated
      groups alters the ground state of H(16)PcFe and gives rise to large changes in
      the ionization potentials and electron affinity. For the six-coordinate adducts
      with acetone, H(2)O, and pyridine, the axial coordination of two weak-field
      ligands leads to an intermediate-spin ground state, while the strong-field
      ligands make the system diamagnetic. The electronic configuration of a ligated
      iron phthalocyanine is determined mainly by the axial ligand-field strength but
      can also be affected by peripheral substituents. Axial ligands also exert an
      effect on ionization potentials and electron affinity and can, as observed
      experimentally, even change the site of oxidation/reduction.

PMID- 15500355
TI  - Synthesis, characterization, and crystal structures of novel intramolecularly
      base-stabilized borane derivatives with six- and seven-membered chelate rings.
AB  - The reaction of (2-dimethylaminophenyl)alcohols 1-HOX-2-NMe(2)C(6)H(4) [X =
      CPh(2) (1), X = CCy(2) (2), X = CPh(2)CH(2) (4)] and 1-phenylaminoalkyl-2
      dimethylaminobenzene 1-HN(Ph)X-2-NMe(2)C(6)H(4) [X = C(H)Ph (3), C(H)PhCH(2) (5)]
      with BH(3)(THF) yielded the BH(2) derivatives 1-H(2)BOX-2-NMe(2)C(6)H(4) [X =
      CPh(2) (6), CCy(2) (7), CPh(2)CH(2) (9)] and 1-H(2)BN(Ph)X-2-NMe(2)C(6)H(4) [X =
      C(H)Ph (8), C(H)PhCH(2) (10)]. Treatment of 1-H(2)BOCPh(2)-2-NMe(2)C(6)H(4) (6)
      with acetic acid gave 1-(CH(3)COO)HBOCPh(2)-2-NMe(2)C(6)H(4) (11). Compounds 6-11
      were characterized spectroscopically (NMR, IR, MS). Crystal structure
      determinations were carried out on 6-11, which are novel examples of structurally
      characterized BH(2) derivatives containing six- or seven-membered chelate rings.
      For the chiral compounds 8, 10, and 11, both enantiomers are present in the unit
      cell.

PMID- 15500356
TI  - Copper(II) complexes with substituted thiosemicarbazones of alpha-ketoglutaric
      acid: synthesis, X-ray structures, DNA binding studies, and nuclease and
      biological activity.
AB  - New alpha-ketoglutaric acid thiosemicarbazone (H(3)ct) derivatives and their
      copper complexes were synthesized and characterized by analytical and
      spectroscopic (IR and NMR) methods. For two of the ligands, Me-H(3)ct and Allyl
      H(3)ct, and for a complex, [Cu(Me-Hct)(OH(2))](n) x 2nH(2)O, the X-ray structures
      were also determined. In the latter the copper atom shows a 4 + 1 pyramidal
      coordination, a water oxygen appears in the apical position, and three of the
      basal positions are occupied by the SNO tridentate ligand and the fourth by a
      carboxylic oxygen of an adjacent molecule that gives rise to a polymeric chain.
      DNA binding constants were determined, and studies of thermal denaturation
      profiles and nuclease activity were also performed. Tests in vitro on human
      leukemia cell line U937 were carried out on cell growth inhibition, cell cycle,
      and apoptosis induction.

PMID- 15500357
TI  - New ligand systems incorporating two and three 4,4'-bipyridine units.
      Characterization of bi- and trimetallic rhodium and iridium complexes.
AB  - The synthesis of new ligand systems based on the bipyridine unit for bi- and
      trimetallic complexes, including a rare example of a chiral bimetallic complex,
      is presented. Ligands BBPX (bis-bipyridine-xylene, 3) and TBPBX (tris-bipyridine
      bis-xylene, 4) were prepared in one step by reacting alpha,alpha'-dibromo-o
      xylene (2) with 2 equiv of the monolithiated derivative of 4,4'-dimethyl-2,2'
      bipyridine. Dilithium (S)-binaphtholate (5) reacted with 2 equiv of 4-bromomethyl
      4'-methyl-2,2'-bipyridine (6), affording ligand (S)-BBPBINAP (bis-bipyridine
      binaphtholate, 7). These ligands reacted cleanly with 1, 1.5, and 1 equiv of the
      rhodium dimer [Rh(2)Cl(2)(HD)(2)] (HD = 1,5-hexadiene), respectively. Chloride
      abstraction led to the isolation of the cationic complexes BBPX[Rh(HD)BF(4)](2)
      (8), TBPBX[Rh(HD)BF(4)](3) (10), and (S)-BBPBINAP[Rh(HD)BF(4)](2) (12). When BBPX
      (3), TBPBX (4), and (S)-BBPBINAP (7) were added to 2, 3, and 2 equiv of
      [Rh(NBD)(2)]BF(4) or [Rh(NBD)(CH(3)CN)(2)]BF(4) (NBD = norbornadiene),
      respectively, clean formation of BBPX[Rh(NBD)BF(4)](2) (9),
      TBPBX[Rh(NBD)BF(4)](3) (11), and (S)-BBPBINAP[Rh(NBD)BF(4)](2) (13) was observed.
      The neutral iridium complex (S)-BBPBINAP[IrCl(COD)](2) (14) was obtained by
      reaction of (S)-BBPBINAP (7) with 1 equiv of [Ir(2)Cl(2)(COD)(2)] (COD =
      cyclooctadiene). The complexes were fully characterized including X-ray
      structural studies of 8, 9, and 13, and preliminary studies on their catalytic
      activity were performed.

PMID- 15500358
TI  - Oxidation of mixed-valence Co(III)/Fe(II) complexes reversed at high pH: a
      kinetico-mechanistic study of water oxidation.
AB  - The outer-sphere oxidation of Fe(II) in the mixed-valence complex trans
      [L(14S)Co(III)NCFe(II)(CN)(6)](-), being L(14S) an N(3)S(2) macrocylic donor set
      on the cobalt(III) center, has been studied. The comparison with the known
      processes of N(5) macrocycle complexes has been carried out in view of the
      important differences occurring on the redox potential of the cobalt center. The
      results indicate that the outer-sphere oxidation reactions with S(2)O(8)(2-) and
      [Co(ox)(3)](3-) involve a great amount of solvent-assisted hydrogen bonding that,
      as a consequence from the change from two amines to sulfur donors, are more
      restricted. This is shown by the more positive values found for DeltaS(#) and
      DeltaV(#). The X-ray structure of the oxidized complex has been determined, and
      it is clearly indicative of the above-mentioned solvent-assisted hydrogen bonding
      between nitrogen and cyanide donors on the cobalt and iron centers, respectively.
      trans-[L(14S)Co(III)NCFe(III)(CN)(6)], as well as the analogous N(5) systems
      trans-[L(14)Co(III)NCFe(III)(CN)(6)], trans-[L(15)Co(III)NCFe(III)(CN)(6)], and
      cis-[L(13)Co(III)NCFe(III)(CN)(6)], oxidize water to hydrogen peroxide at pH > 10
      with a rather simple stoichiometry, i.e., [L(n)()Co(III)NCFe(III)(CN)(5)] + OH(-)
      --> [L(n)()Co(III)NCFe(II)(CN)(5)](-) + (1)/(2)H(2)O(2). In this way, the
      reversibility of the iron oxidation process is achieved. The determination of
      kinetic and thermal and pressure activation parameters for this water to hydrogen
      peroxide oxidation leads to the kinetic determination of a cyanide based OH(-)
      adduct of the complex. A second-order dependence on the base concentration is
      associated with deprotonation of this adduct to produce the final inner-sphere
      reduction process. The activation enthalpies are found to be extremely low (15 to
      35 kJ mol(-1)) and responsible for the very fast reaction observed. The values of
      DeltaS(#) and DeltaV(#) (-76 to -113 J K(-1) mol(-1) and -5.5 to -8.9 cm(3) mol(
      1), respectively) indicate a highly organized but not very compressed transition
      state in agreement with the inner-sphere one-electron transfer from O(2-) to
      Fe(III).

PMID- 15500359
TI  - Reactivity of a (mu-oxo)(mu-hydroxo)diiron(III) diamond core with water, urea,
      substituted ureas, and acetamide.
AB  - A series of iron(III) complexes of the tetradentate ligand BPMEN (N,N'-dimethyl
      N,N'-bis(2-pyridylmethyl)ethane-1,2-diamine) were prepared and structurally
      characterized. Complex [Fe(2)(mu-O)(mu-OH)(BPMEN)(2)](ClO(4))(3) (1) contains a
      (mu-oxo)(mu-hydroxo)diiron(III) diamond core. Complex
      [Fe(BPMEN)(urea)(OEt)](ClO(4))(2) (2) is a rare example of a mononuclear non-heme
      iron(III) alkoxide complex. Complexes [Fe(2)(mu-O)(mu
      OC(NH(2))NH)(BPMEN)(2)](ClO(4))(3) (3) and [Fe(2)(mu-O)(mu
      OC(NHMe)NH)(BPMEN)(2)](ClO(4))(3) (4) feature N,O-bridging deprotonated urea
      ligands. The kinetics and equilibrium of the reactions of 1 with ligands L (L =
      water, urea, 1-methylurea, 1,1-dimethylurea, 1,3-dimethylurea, 1,1,3,3
      tetramethylurea, and acetamide) in acetonitrile solutions were studied by stopped
      flow UV-vis spectrophotometry, NMR, and mass spectrometry. All these ligands
      react with 1 in a rapid equilibrium, opening the four-membered Fe(III)(mu-O)(mu
      OH)Fe(III) core and forming intermediates with a (HO)Fe(III)(mu-O)Fe(III)(L)
      core. The entropy and enthalpy for urea binding through oxygen are DeltaH degrees
      = -25 kJ mol(-1) and DeltaS degrees = -53.4 J mol(-1) K(-1) with an equilibrium
      constant of K(1) = 37 L mol(-1) at 25 degrees C. Addition of methyl groups on one
      of the urea nitrogen did not affect this reaction, but the addition of methyl
      groups on both nitrogens considerably decreased the value of K(1). An opening of
      the hydroxo bridge in the diamond core complex [Fe(2)(mu-O)(mu-OH)(BPMEN)(2)] is
      a rapid associative process, with activation enthalpy of about 60 kJ mol(-1) and
      activation entropies ranging from -25 to -43 J mol(-1) K(-1). For the incoming
      ligands with the -CONH(2) functionality (urea, 1-methylurea, 1,1-dimethylurea,
      and acetamide), a second, slow step occurs, leading to the formation of stable
      N,O-coordinated amidate diiron(III) species such as 3 and 4. The rate of this
      ring-closure reaction is controlled by the steric bulk of the incoming ligand and
      by the acidity of the amide group.

PMID- 15500360
TI  - A platinum-ruthenium dinuclear complex bridged by bis(terpyridyl)xanthene.
AB  - 4,5-Bis(terpyridyl)-2,7-di-tert-butyl-9,9-dimethylxanthene (btpyxa) was prepared
      to serve as a new bridging ligand via Suzuki coupling of terpyridin-4'-yl
      triflate and 2,7-di-tert-butyl-9,9-dimethylxanthene-4,5-diboronic acid. The
      reaction of btpyxa with either 1 equiv or an excess of PtCl(2)(cod) (cod = 1,5
      cyclooctadiene) followed by anion exchange afforded mono- and dinuclear platinum
      complexes [(PtCl)(btpyxa)](PF(6)) ([1](PF(6))) and [(PtCl)(2)(btpyxa)](PF(6))(2)
      ([2](PF(6))(2)), respectively. The X-ray crystallography of [1](PF(6)).CHCl(3)
      revealed that the two terpyridine units in the ligand are nearly parallel to each
      other. The heterodinuclear complex
      [(PtCl)[Ru((t)Bu(2)SQ)(dmso)](btpyxa)](PF(6))(2) ([4](PF(6))(2)) (dmso = dimethyl
      sulfoxide; (t)Bu(2)SQ = 3,5-di-tert-butyl-1,2-benzosemiquinone) and the
      monoruthenium complex [Ru((t)Bu(2)SQ)(dmso)(trpy)](PF(6)) ([5](PF(6))) (trpy =
      2,2':6',2' '-terpyridine) were also synthesized. The CV of [2](2+) suggests
      possible electronic interaction between the two Pt(trpy) groups, whereas such an
      electronic interaction was not suggested by the CV of [4](2+) between Pt(trpy)
      and Ru((t)Bu(2)SQ) frameworks.

PMID- 15500361
TI  - Syntheses and magneto-structural study of several polynuclear copper(II)
      complexes derived from 1,3-Bis(dimethylamino)-2-propanolato.
AB  - The syntheses, structural characterization, and magnetic behavior of the three
      new polynuclear copper(II) complexes with formulas [Cu(4)(eta(2):mu
      CH(3)COO)(2)(mu-OH)(2)(mu-OH(2))(mu-bdmap)(2)](ClO(4))(2).H(2)O (1),
      [Cu(8)(NCO)(2)(eta(1):mu-NCO)(4)(mu-OH)(2)(mu(3)-OH)(2)(mu-OH(2))(3)(mu
      bdmap)(4)](ClO(4))(2)x2H(2)O (2), and [Cu(9)(eta(1):mu-NCO)(8)(mu(3)
      OH)(4)(OH(2))(2)(mu-bdmap)(4)](ClO(4))(2).4H(2)O (3), in which bdmapH is 1,3
      bis(dimethylamino)-2-propanol, are reported. Tetranuclear complex 1 crystallizes
      in the triclinic system, space group P, with unit cell parameters a = 12.160(1)
      A, b = 13.051(1) A, c = 13.235(1) A, alpha = 110.745(1) degrees , beta =
      109.683(1) degrees , gamma = 97.014(1), and Z = 2. Octanuclear complex 2
      crystallizes in the monoclinic system, space group C2/c, with unit cell
      parameters a = 26.609(1) A, b = 14.496(1) A, c = 16.652(1) A, beta = 97.814(1)
      degrees , and Z = 4, and nonanuclear complex 3 crystallizes in the monoclinic
      system, space group C2/c, with unit cell parameters a = 24.104(1) A, b =
      13.542(1) A, c = 24.355(1) A, beta = 109.98(1) degrees , and Z = 4. The magnetic
      behavior of the three complexes has been checked showing strong antiferromagnetic
      coupling in all the cases.

PMID- 15500362
TI  - New details concerning the reactions of nitric oxide with vanadium tetrachloride.
AB  - The slow addition of NO to a CCl(4) solution of VCl(4) reproducibly forms the
      known polymer [V(NO)(3)Cl(2)](n)() as a dark brown powder. Treatment of a
      CH(2)Cl(2) suspension of [V(NO)(3)Cl(2)](n)() with excess THF generates mer
      (THF)(3)V(NO)Cl(2) (1) which can be isolated as an orange crystalline material in
      55% yield. The reaction of 1 with excess MeCN or 1 equiv of trimpsi (trimpsi =
      (t)BuSi(CH(2)PMe(2))(3)) provides yellow-orange (MeCN)(3)V(NO)Cl(2)xMeCN (2xMeCN)
      and yellow (trimpsi)V(NO)Cl(2) (3), respectively. A black, crystalline complex
      formulated as [NO][VCl(5)] (4) is formed by the slow addition of NO to neat
      VCl(4) or by the reaction of excess ClNO with neat VCl(4). Complex 4 is extremely
      air- and moisture-sensitive, and IR spectroscopy suggests that in solutions and
      in the gas phase it dissociates back into VCl(4) and ClNO. Reaction of 4 with
      excess [NEt(3)(CH(2)Ph)]Cl generates [NEt(3)(CH(2)Ph)](2)[VCl(6)]x2CH(2)Cl(2)
      (5x2CH(2)Cl(2)), which can be isolated as deep-red crystals in 51% yield. All new
      complexes have been characterized by conventional spectroscopic methods, and the
      solid-state molecular structures of 1, 2xMeCN, and 5x2CH(2)Cl(2) have been
      established by single-crystal X-ray diffraction analyses.

PMID- 15500363
TI  - Selenolate gold complexes with aurophilic Au(I)-Au(I) and Au(I)-Au(III)
      interactions.
AB  - The gold(I) selenolate compound [Au(2)(SePh)(2)(mu-dppf)] (dppf = 1,1'
      bis(diphenylphosphino)ferrocene) has been prepared by reaction of [Au(2)Cl(2)(mu
      dppf)] with PhSeSiMe(3) in a molar ratio 1:2. This complex reacts with gold(I) or
      gold(III) derivatives to give polynuclear gold(I)-gold(I) or gold(I)-gold(III)
      complexes of the type [Au(4)(mu-SePh)(2)(PPh(3))(2)(mu-dppf)](OTf)(2),
      [Au(3)(C(6)F(5))(3)(mu-SePh)(2)(mu-dppf)], or [Au(4)(C(6)F(5))(6)(mu-SePh)(2)(mu
      dppf)], with bridging selenolate ligands. The reaction of [Au(2)(SePh)(2)(mu
      dppf)] with 1 equiv of AgOTf leads to the formation of the insoluble Ag(SePh) and
      the compound [Au(2)(mu-SePh)(mu-dppf)]OTf. The complexes [Au(4)(C(6)F(5))(6)(mu
      SePh)(2)(mu-dppf)] and [Au(2)(mu-SePh)(mu-dppf)]OTf (two different solvates) have
      been characterized by X-ray diffraction studies and show the presence of weak
      gold(I)-gold(III) interactions in the former and intra- and intermolecular
      gold(I)-gold(I) inter-actions in the later.

PMID- 15500364
TI  - Syntheses and structural characterization of a monomeric tin(II) diamide and a
      novel chlorotin(II) amide trimer.
AB  - We have found that addition of a 2:1 ratio of the bulky ligand
      Li[N(mesityl)(SiMe(3))] to SnCl(2) yields Sn[N(mesityl)(SiMe(3))](2), which is
      found by X-ray crystallography to be monomeric in the solid state. Interestingly,
      the solid state structure of the stannylene exhibits a "minipocket" caused by the
      parallel arrangement of the phenyl rings. A 1:1 ratio of ligand to SnCl(2)
      affords the new chlorotin amide [Sn(mu-Cl)[N(mesityl)(SiMe(3))]](3), which adopts
      a unique trimeric structure in the solid state. The chairlike (Sn-Cl)(3) backbone
      shown here has not been seen previously in Sn-halide chemistry.

PMID- 15500365
TI  - Addition of Pt(PBu(t)(3)) groups to Ru(5)(CO)(12)(eta(6)-C(6)H(6))(mu(5)-C).
      Synthesis, structures, and dynamical activity.
AB  - The reaction of Ru(5)(CO)(12)(eta(6)-C(6)H(6))(mu(5)-C), 7, with Pt(PBu(t)(3))(2)
      yielded two products Ru(5)(CO)(12)(eta(6)-C(6)H(6))(mu(6)-C)[Pt(PBu(t)(3))], 8,
      and Ru(5)(CO)(12)(eta(6)-C(6)H(6))(mu(6)-C)[Pt(PBu(t)(3))](2), 9. Compound 8
      contains a Ru(5)Pt metal core in an open octahedral structure. In solution, 8
      exists as a mixture of two isomers that interconvert rapidly on the NMR time
      scale at 20 degrees C, DeltaH() = 7.1(1) kcal mol(-1), DeltaS() = -5.1(6) cal
      mol(-)(1) K(-)(1), and DeltaG(298)(#) = 8.6(3) kcal mol(-1). Compound 9 is
      structurally similar to 8, but has an additional Pt(PBu(t)(3)) group bridging an
      Ru-Ru edge of the cluster. The two Pt(PBu(t)(3)) groups in 9 rapidly exchange on
      the NMR time scale at 70 degrees C, DeltaH(#) = 9.2(3) kcal mol(-)(1), DeltaS(#)
      = -5(1) cal mol(-)(1) K(-)(1), and DeltaG(298)(#) = 10.7(7) kcal mol(-1).
      Compound 8 reacts with hydrogen to give the dihydrido complex
      Ru(5)(CO)(11)(eta(6)-C(6)H(6))(mu(6)-C)[Pt(PBu(t)(3))](mu-H)(2), 10, in 59%
      yield. This compound consists of a closed Ru(5)Pt octahedron with two hydride
      ligands bridging two of the four Pt-Ru bonds.

PMID- 15500366
TI  - Redox-active polymers based on nonbridged metal-metal bonds. Electrochemical
      formation of [Os(bpy)(CO)(L)](n) (bpy = 2,2'-bipyridine; L = CO, MeCN) and of
      their reduced forms: a spectroelectrochemical study.
AB  - IR, UV-vis, and EPR spectroelectrochemistry at variable temperatures and in
      different solvents were applied to investigate in situ the formation of
      electroactive molecular chains with a nonbridged Os-Os backbone, in particular,
      the polymer [Os(0)(bpy)(CO)(2)](n) (bpy = 2,2'-bipyridine), from a mononuclear
      Os(II) carbonyl precursor, [Os(II)(bpy)(CO)(2)Cl(2)]. The one-electron-reduced
      form, [Os(II)(bpy(.)(-))(CO)(2)Cl(2)](-), has been characterized
      spectroscopically at low temperatures. This radical anion is the key intermediate
      in the electrochemical propagation process responsible for the metal-metal bond
      formation. Unambiguous spectroscopic evidence has been gained also for the
      formation of [[Os(0)(bpy(*)(-))(CO)(2)](-)](n), the electron-rich electrocatalyst
      of CO(2) reduction. The polymer species are fairly well soluble in butyronitrile,
      which is important for their potential utilization in nanoscience, for example,
      as conducting molecular wires. We have also shown that complete solubility is
      accomplished for the monocarbonyl-acetonitrile derivative of the polymer,
      [Os(0)(bpy)(CO)(MeCN)(2)Cl](n).

PMID- 15500367
TI  - Sirolimus- or paclitaxel-eluting stents to prevent coronary artery restenosis.
AB  - The restenosis rate is lower with stent implantation than with balloon
      angioplasty. Nevertheless, even with the use of stenting, restenosis still occurs
      in approximately one-third of patients with diabetes, small coronary vessels, and
      long lesions. The two drugs commonly used in eluting stents are sirolimus and
      paclitaxel. Systemically administered sirolimus decreased vascular proliferation
      in animal models. After preliminary trials showing benefit with sirolimus-eluting
      stents in de novo coronary lesions, the large-scale SIRIUS (Sirolomus-coated Bx
      Velocity balloon-expandable stent in the treatment of patients with de novo
      coronary artery lesions) trial was undertaken. SIRIUS showed that sirolimus
      reduced restenosis and target vessel revascularisation, compared to bare stents.
      These benefits were also apparent in the diabetic, and small- and long vessel
      subgroups. The RESEARCH (Rapamycin-eluting Stent Evaluated At Rotterdam
      Cardiology Hospital) registry have established that sirolimus-eluting stents are
      superior to bare stents in practice. Thus, the benefits of sirolimus-eluting
      stents over bare stents have been clearly established, and sirolimus can be
      considered the benchmark eluting agent for the prevention of coronary artery
      restenosis. Animal studies with paclitaxel-eluting stents, mainly in endothelium
      denuded normal vessels, have shown that paclitaxel reduces restenosis in the
      short-term, and that this may be a delay, rather than a prevention of restenosis.
      In clinical trials, stents eluting the paclitaxel derivative 7-hexanolytaxol, or
      paclitaxel without a polymer, delay rather than prevent restenosis. Slowing the
      release of paclitaxel with a polymer base in the TAXUS (Taxol(trade mark)
      [paclitaxel]-eluting stent) series of clinical trials reduced the
      revascularisation rate at 12 and 18 months, indicating that polymer-based
      paclitaxel is effective for longer. The results of the REALITY trial comparing
      the sirolimus- and paclitaxel-eluting stents in diabetics and other high-risk
      patients are eagerly awaited.

PMID- 15500368
TI  - Vascular restenosis - striving for therapy.
AB  - Restenosis is the limiting entity following coronary angioplasty. It is
      associated with significant morbidity, mortality and cost, and thus represents a
      major clinical and economical problem. Despite technical improvements, restenosis
      after conventional balloon angioplasty occurs in 30 - 60% of cases. Coronary
      stenting was able to reduce the incidence by approximately 30%; nevertheless,
      some 250,000 patients experience in-stent restenotic lesions/year worldwide. In
      stent restenosis has been recognised as very difficult to manage, with a repeat
      restenosis rate of 50%, regardless of the angioplasty device used. So far, only
      vascular brachytherapy has convincingly reduced the incidence of repeat in-stent
      restenosis (by 50%) and thus, has emerged as the gold standard of therapy. The
      introduction of drug-eluting stents has shown a great deal of promise for the
      treatment of both de novo and restenotic lesions, with reported restenosis rates
      of < 10%, and benefit for virtually all patient subsets at a higher risk of
      restenosis. This review outlines the pathophysiology, epidemiology and predictors
      of the restenosis process, and places emphasis on the various treatment options
      for its prevention and therapy.

PMID- 15500369
TI  - Recent progress in the therapeutic management of pre-eclampsia.
AB  - Pre-eclampsia is a pregnancy-specific syndrome of unknown aetiology, observed in
      3 - 5% of all pregnancies, associated with pathological vascular lesions in
      multiple organs, activation of the coagulation system, and maternal multisystemic
      and fetal complications. Clinically, pre-eclampsia is characterised by the onset
      of hypertension, proteinuria and oedema, usually beginning in the third
      trimester. Conventionally, antihypertensive agents are the main pharmacological
      treatment. Recently, some studies have shown that the treatment of pre-eclampsia
      with antithrombin concentrate corrects the hypercoagulability and improves the
      fetal status and the perinatal outcome. No clear evidence supports the use of
      heparin. A conservative treatment of moderate- to- severe pre-eclampsia, based on
      the administration of antithrombin concentrate, may allow a significant
      prolongation of pregnancy and a better neonatal outcome, as well as fewer
      maternal complications.

PMID- 15500370
TI  - New phosphodiesterase inhibitors in the treatment of erectile dysfunction.
AB  - Sildenafil revolutionised the treatment of erectile dysfunction (ED) on its
      introduction in 1998. Not only is it effective, but is, perhaps even more
      importantly, an extremely acceptable manner in which to treat ED (i.e., oral
      pharmacotherapy), compared to the other treatments that were available at that
      time (e.g., intracavernosal injection). Whilst sildenafil remains the market
      leader for ED treatment, it does have some shortcomings: its clinical efficacy is
      diminished in 'difficult to treat' patient groups, such as diabetics, side
      effects, such as blue-tinged vision and headache, and the need to time the
      ingestion of sildenafil to 1 h prior to expected time of sexual intercourse.
      Recently, newer phosphodiesterase inhibitors ('sons of viagra') have become
      available, and potentially to improve upon, what has become regarded as the gold
      standard for ED treatment. This review article discusses the differences between
      vardenafil, tadalafil and sildenafil, in order to allow the clinician to make an
      informed decision as to which phosphodiesterase inhibitor to prescribe when
      dealing with the ever expanding number of patients seeking help for ED.

PMID- 15500371
TI  - Current pharmacological treatment of gastroparesis.
AB  - The aetiology of gastroparesis differs between children and adults. During
      childhood, gastroparesis is quite rare, and is mostly seen in preterm infants,
      with either immaturity of the gastrointestinal tract, or when allergic to cow's
      milk protein. Acute, delayed gastric emptying may be observed following viral
      infections. In adults, most patients with gastroparesis are either idiopathic or
      of diabetic origin. As a consequence, approaches in the treatment of children and
      adults differ. Metoclopramide, domperidone, cisapride and erythromycin have all
      been studied. Evidence for benefit is strongest for the latter two drugs,
      although most studies have methodological shortcomings. From a paediatric
      perspective, it seems astonishing that more trials with erythromycin analogues
      have not been performed, as the few data available suggests that these analogues
      are more powerful, without the side effects of long-term, low-dose administration
      of antibiotics. Gastric electrical stimulation seems the most promising
      therapeutic option available at present.

PMID- 15500372
TI  - Pharmacological treatment of nephropathic cystinosis with cysteamine.
AB  - Cystinosis, clinically recognised since 1903, is an autosomal recessive lysosomal
      storage disease caused by mutations in CTNS. This gene codes for a lysosomal
      cystine transporter, whose absence leads to intracellular cystine crystals,
      widespread cellular destruction, renal Fanconi syndrome in infancy, renal
      glomerular failure in later childhood and other systemic complications. Before
      the availability of kidney transplantation, patients affected with cystinosis
      uniformly died during childhood. After solid organ transplantations became
      successful in the 1960s, cystinosis patients survived, but eventually developed
      life-threatening consequences of the disease (e.g., swallowing disorders). Since
      the introduction of cysteamine into the pharmacological management of cystinosis,
      well-treated adolescent and young adult patients have experienced normal growth
      and maintenance of renal glomerular function. Oral cysteamine therapy is given at
      doses of 60 - 90 mg/kg/day q.i.d. every 6 h, and generally achieves approximately
      90% depletion of cellular cystine, as measured in circulating leucocytes.
      Cysteamine (and kidney transplantation) have commuted the death sentence of
      cystinosis into a nearly normal life with a chronic disease. Because treatment
      with oral cysteamine can prevent, or significantly delay, the complications of
      cystinosis, early and accurate diagnosis, as well as proper treatment, is
      critical.

PMID- 15500373
TI  - Lupus nephritis: a review of the current pharmacological treatments.
AB  - Proliferative lupus glomerulonephritis World Health Organization Class III and IV
      patients should benefit from an induction and maintenance therapy with a combined
      immunosuppressive treatment. Cyclophosphamide is the main recommended drug in
      induction therapy for a 3- to 6-month treatment period. Refractory lupus
      nephritis may be considered for immunoablative cyclophosphamide treatment with or
      without haematopoietic CD34(+) stem-cell transplantation or rituximab.
      Maintenance therapy should contain either quarterly cyclophosphamide pulses,
      azathioprine or mycophenolate mofetil for a total treatment duration of at least
      2 years. Recent studies suggested a similar efficacy of mycophenolate mofetil and
      cyclophosphamide in induction and maintenance therapy. This result has to be
      confirmed in long-term studies.

PMID- 15500374
TI  - The role of growth hormone-receptor antagonism in relation to acromegaly.
AB  - Acromegaly is a rare but disabling condition associated with reduced life
      expectancy. It is caused almost invariably by a growth hormone-secreting
      pituitary adenoma. Transsphenoidal surgery and/or radiotherapy are still
      considered to be the treatment of choice, but despite recent advances in both
      these forms of treatment, the overall surgical cure rate remains approximately
      60%, and radiotherapy is characterised by delayed effect and a high incidence of
      hypopituitarism. Medical therapy in the form of dopamine agonists and
      somatostatin analogues has traditionally been used as an adjunct to surgery
      and/or radiotherapy, but is increasingly being used as first line therapy in the
      treatment of acromegaly. Recently, a third form of medical therapy, the growth
      hormone receptor antagonist, pegvisomant, has been licensed for use in
      acromegaly. This article examines the design, properties, clinical efficacy and
      safety of pegvisomant.

PMID- 15500375
TI  - Available pharmacological treatments for anorexia nervosa.
AB  - Currently, no medications are approved by the FDA for the treatment of anorexia
      nervosa (AN). However, there are several promising pharmacological targets.
      Treatment includes a weight restoration and a weight maintenance phase and
      different pharmacological treatments may be useful in one phase, but not the
      other. Although cyproheptadine has some modest benefit during the weight
      restoration phase, it is not widely used. Fluoxetine administered during the
      weight maintenance phase decreases relapse rate. The medications currently being
      most widely studied are the atypical antipsychotics, particularly olanzapine.
      Emerging evidence suggests that some AN patients have psychotic symptoms that may
      respond to antipsychotic agents. There are promising case reports and open-label
      studies of the atypical antipsychotics, but as yet, no randomised, placebo
      controlled, double-blind studies have been reported. Additional novel treatment
      approaches are urgently needed for this group of severely ill patients who have a
      high premature mortality rate.

PMID- 15500376
TI  - Treatment strategies in controlling strongyloidiasis.
AB  - Strongyloidiasis is an intestinal parasite infection caused by Strongyloides
      stercoralis. Spontaneous cure cannot be expected due to the unique life cycle of
      the parasite, termed autoinfection. The disease occurs worldwide, but especially
      in tropical and subtropical regions. Serious clinical problems with complications
      and refractory strongyloidiasis are observed, especially in immunocompromised
      patients, such as those infected with human T cell leukaemia virus Type 1 (HTLV
      1) or HIV, or corticosteroid-treated patients. Thiabendazole is effective against
      S. stercoralis infection; however, serious side effects have been reported.
      Recently, ivermectin, which has been introduced for the treatment of human
      onchocerciasis, has been reported to be effective against strongyloidiasis,
      without serious side effects. The interval of administration is important for
      treatment, because if autoinfective migrating larvae are not eradicated, S.
      stercoralis will resume its life cycle and multiply again. To evaluate the
      results of treatment of S. stercoralis, stool examinations and S. stercoralis
      specific antibody titres should be examined for at least 1 or 2 years if
      possible. This article provides a review of treatments and methods of evaluation
      of patients infected with S. stercoralis.

PMID- 15500377
TI  - Telmisartan/hydrochlorothiazide combination therapy in the treatment of essential
      hypertension.
AB  - Telmisartan is an angiotensin-II receptor blocker that has demonstrated efficacy
      in the reduction of blood pressure in patients with hypertension. Patients with
      hypertension commonly require two or more antihypertensives to reduce their blood
      pressure to safe levels, and the choice of combination therapy should be informed
      by clinical trial data. Telmisartan is available in fixed-dose combination with
      hydrochlorothiazide (telmisartan/HCTZ) in doses of 40 mg/12.5 mg and 80 mg/12.5
      mg. Telmisartan/HCTZ has been studied in a number of clinical trials in essential
      hypertension, for the most part using ambulatory blood pressure monitoring. It
      has been compared with monotherapy in full patient populations and in non
      responders, and has been compared with other drug combinations. Telmisartan/HCTZ
      provides significantly greater reductions in blood pressure than monotherapy, and
      significantly increases the percentage of patients who achieve target blood
      pressure. The reduction in blood pressure achieved by adding HCTZ to telmisartan
      is greater than that achieved by adding HCTZ to atenolol, despite the fact that
      telmisartan and atenolol monotherapy had similar efficacy. Telmisartan/HCTZ
      provides significantly greater reductions than losartan plus HCTZ in 24-h mean
      blood pressure, primarily due to a significantly greater effect in the risky,
      early morning hours. Telmisartan/HCTZ is effective and well-tolerated in the
      elderly, diabetics and African-American patients. Ongoing studies are comparing
      the efficacy of telmisartan/HCTZ with valsartan plus HCTZ and amlodipine plus
      HCTZ in overweight, hypertensive diabetics and in patients with isolated systolic
      hypertension - two patient groups who are particularly at risk of target organ
      damage.

PMID- 15500378
TI  - Losartan for the treatment of hypertension and left ventricular hypertrophy: the
      Losartan Intervention For Endpoint reduction in hypertension (LIFE) study.
AB  - Losartan is an orally active, selective, nonpeptide, angiotensin-II Type I
      receptor antagonist, and was the first drug marketed in this class. It has been
      approved for the treatment of hypertension, and may be used alone or in
      combination with other antihypertensive agents. Based on the Losartan
      Intervention For Endpoint reduction in hypertension (LIFE) study, losartan has
      been approved for the reduction of cardiovascular events in patients with
      hypertension and left ventricular hypertrophy, but there is evidence that this
      benefit does not apply to black patients. Based on the Reduction of Endpoints in
      NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study, losartan is
      also indicated for the treatment of diabetic nephropathy with an elevated serum
      creatinine and proteinuria, in patients with Type 2 diabetes. The focus of this
      review is the LIFE study.

PMID- 15500379
TI  - Daptomycin - a novel antibiotic against Gram-positive pathogens.
AB  - Daptomycin is a novel member of a new class of antimicrobial agents used in
      treating resistant Gram-positive infections. These infections are becoming more
      commonplace and treatment options are limited. At present, daptomycin is approved
      for use in the US for complicated skin and skin-structure infections that are a
      common complication of surgery, diabetic foot ulcers, and burns. The most common
      causative organisms in these types of infections are Staphylococcus aureus,
      Streptococcus pyogenes, Streptococcus agalactiae, and Group C and G streptococci.
      Traditionally, these infections have been treated with penicillin and
      cephalosporins, but resistance to these agents is widespread and increasing. Of
      particular concern is the rapid increase in methicillin-resistant S. aureus
      (MRSA). The SENTRY Antimicrobial Surveillance Programme reported that
      approximately 30% of S. aureus isolates from skin and skin-structure infections
      were MRSA. The standard treatment for MRSA infections is vancomycin but
      resistance to this agent is also developing. There is a continuing need for the
      development of new antibiotics with Gram-positive activity, to combat multi-drug
      resistant Gram-positive infections.

PMID- 15500380
TI  - Review of the use of topotecan in ovarian carcinoma.
AB  - Ovarian cancer is the fifth leading cause of cancer deaths in women. The majority
      of patients present with advanced disease and relapse after first-line platinum
      based chemotherapy; therefore, many proceed to treatment with salvage
      chemotherapy. Currently available treatment options are generally no longer
      curative in the relapse setting; hence, the emphasis of treatment is towards
      disease control and palliation of symptoms. There are several agents available
      for the treatment of relapsed ovarian carcinoma, of which topotecan is one of the
      most widely studied and characterised. This review aims to evaluate the role of
      topotecan in the management of this disease by considering the properties of the
      compound, the clinical efficacy in Phase II and III studies, its role in first-
      and second-line treatment and alternative dosing strategies to overcome toxicity.

PMID- 15500381
TI  - Efficacy and safety of ibandronate in the treatment of neoplastic bone disease.
AB  - Bone is an organ commonly involved in spreading neoplastic disease, especially in
      multiple myeloma and carcinoma of the breast, prostate and lung. Skeletal
      stabilisation and pain relief are the main treatment goals in metastatic bone
      disease. Bisphosphonate treatment inhibits osseous breakdown and is well
      established as the current standard therapy for reducing complications of
      neoplastic bone disease (e.g., pain, fractures and hypercalcaemia). Ibandronate
      is a third-generation bisphosphonate that has recently been approved for the
      treatment of bone metastases caused by breast cancer. The oral and intravenous
      formulations of ibandronate appear to have comparable efficacy. Ibandronate has
      also been shown to provide significant and sustained relief from metastatic bone
      pain over 2 years of treatment, improving patient functioning and quality of
      life. With a favourable long-term safety profile and the added convenience and
      flexibility offered by its efficacious oral formulation, ibandronate represents a
      new therapeutic option for metastatic bone disease management.

PMID- 15500382
TI  - Oxybutynin for treatment of urge urinary incontinence and overactive bladder: an
      updated review.
AB  - Urge urinary incontinence (UUI) and overactive bladder are common conditions
      often associated with profound impairment of the health and quality of life of
      the patient. Antimuscarinic medications have been the mainstay of treatment for
      these disorders. Oxybutynin hydrochloride, one of the most widely used
      antimuscarinic agents, has attracted considerable interest from both clinicians
      and pharmacologists over the last three decades. Although efficacy of this drug
      has been proven to be high, its use is limited by antimuscarinic adverse effects,
      possibly related to its active metabolite N-desethyloxybutynin (N-DEO). The
      extended-release form of oxybutynin uses a push-pull osmotic release system which
      has significantly improved its tolerability and safety profile. A transdermal
      transport system has also been developed, bypassing the first-pass metabolism in
      the liver and gut. This system is associated with significant reduction in the
      production of the primary metabolite and additional improvement in the
      tolerability profile of the drug. Intravesical instillation of oxybutynin has
      been reported although the efficacy and safety of this delivery system has yet to
      be determined. This article comprehensively reviews the contemporary literature
      on the pharmacology, clinical efficacy and adverse reactions of oxybutynin in its
      various delivery forms, and compares them to other frequently used medications
      for UUI and overactive bladder.

PMID- 15500383
TI  - Adefovir dipivoxil in chronic hepatitis B infection.
AB  - Adefovir dipivoxil, an acyclic nucleotide analogue, is effective for the
      treatment of chronic hepatitis B in both hepatitis B e antigen (HBeAg)-positive
      and -negative patients, with improvement in liver histology, hepatitis B virus
      (HBV) DNA levels, alanine aminotransferase levels, and HBeAg seroconversion (for
      HBeAg-positive patients). It is also effective against lamivudine-resistant
      strains of hepatitis B mutations. It has been studied in pre- and post-liver
      transplant patients. Compared to lamivudine, adefovir dipivoxil is associated
      with a much lower risk of emergence of drug-resistant HBV. Adefovir-associated
      resistant virus is susceptible to lamivudine therapy. The recommended dose of
      adefovir dipivoxil 10 mg is associated with low risk of nephrotoxicity. Adefovir
      dipivoxil can be recommended as a first-line treatment but can also be used in
      patients with chronic hepatitis B infection who are failing lamivudine therapy.

PMID- 15500384
TI  - Review of tegaserod in the treatment of irritable bowel syndrome.
AB  - Tegaserod is a drug in a new class of compounds called aminoguanidine indoles and
      is structurally similar to serotonin (5-HT) with modifications that make the drug
      selective for the 5-HT(4) receptor. Tegaserod has a stimulatory effect on
      gastrointestinal (GI) motility that has been demonstrated in animal studies and
      in healthy adults. Tegaserod also increases GI secretion and reduces rectal
      sensitivity. Tegaserod is currently approved by the FDA for the treatment of
      women with constipation-predominant irritable bowel syndrome (C-IBS). Eight large
      Phase III clinical trials involving > 5000 IBS patients support the clinical
      efficacy of tegaserod in this group of patients. Patients who were treated with
      tegaserod had an overall improvement in IBS symptoms (Subject's Assessment of
      Global Relief) as well as in secondary end points, such as abdominal pain and
      discomfort, stool consistency, change in bowel movements and relief of bloating.
      Tegaserod was well-tolerated. The most common adverse reaction in clinical trials
      was diarrhoea, which was usually temporary and mild, although severe diarrhoea
      requiring hospitalisation has been rarely (< 1%) reported.

PMID- 15500385
TI  - Clinical-economic appropriateness of drug treatments: designing a method that
      combines evidence-based information and cost assessments to construct league
      tables accounting for the potential number of patients.
AB  - This paper presents a method to assess drug treatment appropriateness, based on
      an original combination of economic analysis, pharmacoepidemiological techniques
      and evidence-based information. This method generates an index of clinical
      economic appropriateness for the treatment under examination, by comparing the
      theoretically expected health gain (EHG) to the yearly national expenditure
      (EXPEND) on that drug and the amount of health that is thought to be gained in
      the 'real' patients (RHG). This paper reviews all the analyses conducted so far
      using this method, and discusses their main results. The primary aim of this
      article is to suggest a ranking approach for allocating the drug budgets of
      national health systems.

PMID- 15500386
TI  - Therapeutic approaches in treating Creutzfeldt-Jakob disease - what does the
      future hold?
AB  - Creutzfeldt-Jakob disease (CJD) is one of the human prion disorders. It has a
      rapid disease course and is invariably fatal. Currently, no therapy is available.
      The causative agent is thought to be the prion protein, which acquires a
      pathological isoform through a conformational change and is hardly degradable.
      Experimental research has identified several substances, which were able to
      modestly inhibit the formation and propagation of pathological prion
      configurations. However, these substances were only effective when administered
      around the time of inoculation with the pathological prion. This review discusses
      the possibilities and limitations encountered in the development of
      pharmacotherapeutics for CJD.

PMID- 15500387
TI  - Telmisartan - killing two birds with one stone.
AB  - In theory, a drug that inhibits the renin-angiotensin system in order to lower
      blood pressure and acts as a PPARgamma agonist to increase insulin sensitivity,
      could be very useful in the treatment of coexisting Type 2 diabetes and
      hypertension. Telmisartan is an angiotensin Type 1 (AT(1))-receptor antagonist
      being used in the treatment of hypertension. Recent studies suggest that
      telmisartan is also a partial PPARgamma agonist. In an animal model of insulin
      resistance, telmisartan lowered serum levels of glucose, insulin and
      triglycerides, and body weight. Thus, telmisartan, an AT(1)-receptor antagonist
      and PPARgamma agonist, represents the prototype of a new approach to treating
      coexisting diabetes and hypertension, which needs to be evaluated clinically.

PMID- 15500388
TI  - Peroxisome proliferator-activated receptor ligands in atherosclerosis.
AB  - In this review, the effect of peroxisome proliferator-activated receptor (PPAR)
      ligands on atherosclerosis is examined. The PPAR-gamma agonist thiazolidinediones
      are currently indicated for the management of Type 2 diabetes mellitus, and the
      PPAR-alpha agonist fibrates are used in dyslipidaemia. Here their mechanism of
      action and the pre-clinical and clinical evidence for the use of these
      medications for the prevention and treatment of atherosclerotic disease is
      explored. In addition, the role of PPAR-delta and the possibilities for the role
      of dual-binding agonists are examined.

PMID- 15500389
TI  - Lipid-lowering therapies in development.
AB  - Lipid lowering is established as a proven intervention to reduce atherosclerosis
      and its complications. This article summarises novel developments in the lipid
      altering therapies under development, including combination therapies, squalene
      synthase inhibitors, microsomal transfer protein inhibitors, acyl-cholesterol
      acyl transferase inhibitors, cholesterol ester transfer protein antagonists,
      peroxisome proliferator-activated receptor agonists, high-density lipoprotein
      derived peptides and inflammation inhibitors, which have at least reached trials
      in animal models. Lipid-altering drugs are likely to to be a fast-developing area
      for novel treatments as possible synergies exist between new and established
      compounds for the treatment of atherosclerosis. New agents will have to show
      significant advantage in tolerability or efficacy over existing agents and have
      the potential to be used in combination therapy as is well established for bile
      acid sequestrants, nicotinic acid or fibrates and statins. Any new drugs will
      also have to be assessed in clinical end-point trials against current compounds
      with proven outcome benefits.

PMID- 15500390
TI  - The potential of endothelin antagonism as a therapeutic approach.
AB  - Endothelin (ET) is a pivotal physiological regulator of blood pressure through
      its effects on blood vessels, heart, lung and kidneys, and the ET system can be
      overactive in disorders such as pulmonary hypertension, heart failure and renal
      disease. Such observations stimulated interest among scientists and
      pharmaceutical companies that have set up high-throughput screens to search for
      antagonists of ET receptors. The emerging compounds have been tested in animals
      with exciting results, leading to great hope that such inhibitors could be
      translated into human drugs with desirable therapeutic activities and few side
      effects. This review will describe the most relevant results obtained in
      experimental animals in a wide variety of disease conditions and focus on the
      data of selected compounds that have been employed in clinical trials.

PMID- 15500391
TI  - The analgesic potential of clostridial neurotoxin derivatives.
AB  - Botulinum neurotoxins are the most potent acute lethal toxins known, and yet for
      the last two decades they, and in particular serotype A, have found increasing
      use in the clinical treatment of diseases or conditions involving neuromuscular
      or autonomic neuronal transmission. The neurotoxins work by inhibiting the
      release of acetylcholine from peripheral cholinergic nerve terminals. More
      recently, the effects on non-cholinergic pathways have been identified, and this
      has led to an increase in the diseases and syndromes for which botulinum
      neurotoxins have been found to have clinical utility. In particular, botulinum
      neurotoxins have been demonstrated to potentially benefit a range of chronic pain
      syndromes. With the description in the last decade of the biochemical basis of
      neurotoxin action and the tertiary structure of the toxin molecule, the
      possibility of designing novel agents utilising selected aspects of toxin
      function has arisen. This possibility has been pursued in the context of pain
      relief with the description of a novel hybrid protein derived from botulinum
      neurotoxin type A, LH(N)/A-ECL, able to selectively target nociceptive afferent
      neurons and inhibit the release of neurotransmitters involved in pain
      transmission. This novel derivative of botulinum neurotoxin type A demonstrates
      prolonged analgesic activity in vivo. This review will consider the evidence for
      the analgesic properties of the botulinum neurotoxins and their suitability as
      the basis for novel therapeutic proteins. The general concept of deriving novel
      therapeutic molecules from the neurotoxins will also be considered.

PMID- 15500392
TI  - Recent developments in transient receptor potential vanilloid receptor 1 agonist
      based therapies.
AB  - Capsaicin and other naturally occurring pungent molecules have been used for
      centuries as topical analgesics and rubefactants to treat a variety of
      chronically painful conditions. Recently, instillations of high-concentration
      capsaicin and resiniferatoxin solutions have been found to be useful for the
      management of persistent bladder pain or overactive bladder. However, only within
      the last 7 years has it been appreciated that the selective action of these
      compounds on a subset of sensory nerve fibres is mediated by agonist activity at
      a ligand-gated ion channel called the transient receptor potential vanilloid
      receptor 1 (TRPV1). Accordingly, this discovery has fueled intensive research and
      drug development efforts, mainly in a search for novel analgesic or anti
      inflammatory therapies. Two different, but non-mutually exclusive, strategies are
      being pursued: optimisation of TRPV1 agonist-based therapies, which can
      functionally inactivate nociceptive nerve fibres, and identification of receptor
      antagonists, which would prevent nociceptive fibres from being activated by
      ongoing inflammatory stimuli. Available information on TRPV1 agonists in
      development and their biological rationale will be summarised in this review.

PMID- 15500393
TI  - Selective oestrogen receptor modulators in desmoid tumours.
AB  - Selective oestrogen receptor modulators (SERMs) are compounds with a mixed
      agonist/antagonist activity on oestrogen receptors. An ideal SERM is a compound
      with an oestrogen antagonist effect on the breast and uterus but oestrogen
      agonist effect on bone. Beside tamoxifen, a group of well-investigated SERMs is
      represented by raloxifene, LY-353381 (SERM3), EM-800 and CP-336156. On an
      empirical basis, tamoxifen has been used to pharmacologically treat desmoid
      tumours. Recently, raloxifene, a second-generation SERM, has been used in the
      treatment of familial adenomatous polyposis patients affected by desmoid tumour.
      The mechanisms through which these molecules affect desmoid tumour growth appear
      to be due, in part, to the fact that SERMs may act independently of oestrogen
      receptors. The knowledge of the molecular basis of SERM action will make the
      development of novel synthetic compounds with engineered tissue selectivity
      possible.

PMID- 15500394
TI  - The potential role of non-steroidal anti-inflammatory drugs in treating
      Alzheimer's disease.
AB  - Epidemiological studies suggest that long-term use of non-steroidal anti
      inflammatory drugs (NSAIDs) may protect against Alzheimer's disease (AD). Despite
      encouraging evidence, all large, long-term, placebo-controlled clinical trials
      aimed at reducing inflammation in the brain of AD patients produced negative
      results. More recently it has been shown that some NSAIDs decrease the production
      of amyloid-beta(1-42) (Abeta42), the major component of senile plaques of the AD
      brain, and counteract the progression of Abeta42 pathology in transgenic mouse
      models of AD. The proposed mechanism for this activity is an allosteric
      modulation of gamma-secretase activity, the enzyme responsible for the formation
      of amyloid-beta. The inhibition of Abeta42 production is independent from the
      anti-cyclooxygenase (COX) activity and is related to the chemical structure of
      the compounds, with some NSAIDs being active (ibuprofen, sulindac, flurbiprofen,
      indomethacin, diclofenac) and others not (naproxen, aspirin, celecoxib). This
      could explain the negative results of the large AD trials carried out so far, as
      they were conducted with compounds (naproxen, hydroxychloroquine, dapsone,
      prednisone, rofecoxib and celecoxib) that are not able to decrease Abeta42
      production. Unfortunately, the use of these NSAIDs in AD is hampered by a
      significant gastrointestinal toxicity associated with COX inhibition. Thus, new
      NSAID analogues are being developed with potent and selective inhibitory activity
      on Abeta42 but with either lack of COX inhibitory activity or reduced
      gastrointestinal toxicity potential.

PMID- 15500395
TI  - Sitaxsentan, a selective endothelin-A receptor antagonist for the treatment of
      pulmonary arterial hypertension.
AB  - Sitaxsentan, a highly selective endothelin-A (ET(A)) receptor antagonist (6500
      fold more selective for ET(A) receptors than endothelin-B (ET(B)) receptors), may
      benefit patients with pulmonary artery hypertension (PAH) by blocking the
      vasoconstrictor effects of ET(A) receptors while maintaining the
      vasodilator/clearance functions of ET(B) receptors. In its first randomised,
      placebo-controlled study, Sitaxsentan to Relieve Impaired Exercise-1 (STRIDE-1),
      sitaxsentan improved exercise capacity assessed by 6 min walk, New York Heart
      Association functional class, cardiac index and pulmonary vascular resistance in
      New York Heart Association class II, III and IV patients with idiopathic PAH, PAH
      related to connective tissue disease or PAH related to congenital heart disease.
      In STRIDE-1, doses of 100 and 300 mg/day p.o. were evaluated. Although both doses
      showed equivalent efficacy, the lower dose had a more tolerable safety profile.
      Additional studies are ongoing to assess the relative safety and efficacy of 50
      and 100 mg/day doses, both in de novo patients and in patients previously treated
      with the ET(A)/ET(B) receptor antagonist bosentan. Long-term comparative studies
      are necessary to determine whether there is a clinically meaningful difference
      between selective ET(A) receptor antagonism and ET(A)/ET(B) receptor antagonism.

PMID- 15500396
TI  - Darifenacin: a novel M3 muscarinic selective receptor antagonist for the
      treatment of overactive bladder.
AB  - Darifenacin is a novel M3 muscarinic selective receptor antagonist for once-daily
      treatment of overactive bladder (OAB), a highly prevalent, chronic and
      debilitating disease defined by urinary urgency with or without urge
      incontinence, usually with increased frequency of micturition and nocturia. In
      vitro, darifenacin is a potent and specific muscarinic receptor antagonist with
      </= 59-fold higher selectivity for muscarinic M3 receptors relative to other
      muscarinic receptor subtypes. This profile may, therefore, confer clinical
      efficacy in the treatment of OAB, with a lower propensity for adverse effects and
      safety issues related to blockade of other muscarinic receptor subtypes. Indeed,
      consistent with its low relative affinity for M1 and M2 receptors, no effects on
      cognitive function and heart-rate variability, respectively, have been observed
      with darifenacin. Subsequent large-scale clinical trials have confirmed that
      darifenacin (at doses of 7.5 and 15 mg/day) results in central nervous system and
      cardiac adverse events comparable to placebo, and provides early and meaningful
      improvement across a range of OAB symptoms including incontinence episodes,
      urgency and urinary frequency. On the basis of such findings, darifenacin would
      appear to meet the current need for an effective OAB pharmacotherapy that is
      efficacious, well-tolerated and, more importantly, minimises the risk of safety
      related adverse effects.

PMID- 15500397
TI  - CT-2103: emerging utility and therapy for solid tumours.
AB  - CT-2103 (XYOTAX, Cell Therapeutics, Inc.) is a conjugate of paclitaxel to a
      polyglutamate polymer. Its macromolecular nature exploits enhanced permeability
      and retention in tumour tissues. This compound is stable and inactive in aqueous
      solution and undergoes predominantly intracellular metabolism at the site where
      active paclitaxel is released. Because it does not require a Cremophor EL
      vehicle, it can be administered by short infusion into peripheral veins. In
      preclinical models, compared with the same dose of unconjugated paclitaxel in
      Cremophor EL-ethanol, CT-2103 yields >or= 12-fold increase in area under the
      curve in both plasma and tumour tissue. This alteration in drug pharmacokinetics
      and biodistribution is attributable to the ability of macromolecules to
      concentrate in areas of vascular leakiness, such as tumour tissue. CT-2103 is
      taken up by both tumour cells and normal phagocytic cells and is transported to
      lysosomes, where it is released by specific proteases through enzymatic action.
      In syngeneic and xenogeneic tumour models, at the maximally tolerated dose, CT
      2103 appears to be more active than the standard doses of paclitaxel. It has also
      demonstrated activity in paclitaxel-resistant tumour models. Its potential
      enhancement of efficacy and decrease in drug-related toxicities make this agent
      an attractive option for therapeutic investigation. In Phase I trials it has been
      relatively well-tolerated, with acceptable toxicity at doses <or= 225 mg/m(2)
      every 3 weeks. In combination with carboplatin the maximum tolerated dose is 235
      mg/m(2) and the recommended Phase II dose 210 mg/m(2). Activity has been
      demonstrated in both non-small cell lung carcinoma (NSCLC) and in ovarian cancer,
      Phase III studies are currently testing this agent versus standard paclitaxel as
      maintenance therapy for first-line treatment-naive ovarian cancer. In addition,
      CT-2103 at a dose of 210 mg/m(2) (performance status [PS] 0 - 1) or 175 mg/m(2)
      (PS 2) is being compared with docetaxel (75 mg/m(2)) for the second-line
      treatment of NSCLC. In front-line PS 2 NSCLC patients, this agent in combination
      with carboplatin is undergoing comparison with paclitaxel/carboplatin; in a
      separate effort, single-agent CT-2103 is being compared with either gemcitabine
      or vinorelbine. These studies will determine whether the preclinical and early
      clinical promise of this agent can be realised in the clinical treatment of solid
      tumours.

PMID- 15500398
TI  - Rationale, design and organisation of an efficacy and safety study of oxypurinol
      added to standard therapy in patients with NYHA class III - IV congestive heart
      failure.
AB  - Oxypurinol, the active metabolite of allopurinol and a potent xanthine oxidase
      inhibitor (XOI), is under evaluation as a novel agent for the treatment of
      congestive heart failure (HF). Several lines of evidence provide the rationale
      for the hypothesis that XOIs will improve clinical outcomes in patients with HF.
      First, XOIs have unique positive inotropic effects, improving myocardial
      contraction and performance while simultaneously improving myocardial energy
      metabolism. Second, XOIs ameliorate endothelial dysfunction in humans with HF.
      Finally, XO activity is upregulated in the heart and vasculature of subjects with
      HF, which may in turn contribute to oxidative stress and/or increased uric acid
      levels. Together these findings form the rationale for the Controlled Efficacy
      and Safety Study of Oxypurinol Added to Standard Therapy in Patients with New
      York Heart Association (NYHA) class III - IV Congestive Heart Failure (OPT-CHF)
      trial (Food and Drug Administration IND 65,125), a Phase II - III prospective,
      randomised, double-blind, placebo-controlled trial, which will include patients
      with stable symptomatic HF in NYHA class III - IV congestive HF who are deemed
      clinically stable on a standard and appropriately maximised heart failure therapy
      regimen. The efficacy end point for OPT-CHF is a composite that incorporates
      measures of patient outcome and well-being.

PMID- 15500399
TI  - A neuroprotective derivative of erythropoietin that is not erythropoietic.
AB  - In addition to its well-known erythropoetic effect, erythropoietin (EPO) has also
      been shown to be neuroprotective in various animal models. In contrast to EPO,
      carbamylated EPO (CEPO) does not bind to the EPO receptor on UT7 cells or have
      any haematopoietic/proliferative activity on these cells. In vivo studies in mice
      and rats showed that even high doses of CEPO for long periods are not
      erythropoietic. However, in common with EPO, CEPO does inhibit the apoptosis
      associated with glutamate toxicity in hippocampal cells. Like EPO, CEPO is
      neuroprotective in a wide range of animal models of neurotoxicity: middle
      cerebral artery occlusion model of ischaemic stroke, sciatic nerve compression,
      spinal cord depression, experimental autoimmune encephalomyelitis and peripheral
      diabetic neuropathy. To date, EPO and CEPO have been exciting developments in the
      quest for the treatment of various types of neurotoxicity. The development of
      CEPO should continue.

PMID- 15500400
TI  - Biological response modifiers for the treatment of Crohn's disease.
AB  - Although standard medical therapy in Crohn's disease is efficient in most
      patients, a substantial proportion of patients suffering from chronic active
      disease do not adequately respond to standard therapy. In these patients,
      alternative regimens have to be considered. Due to the major advances in
      understanding the pathogenesis of this complex disease involving genetic,
      environmental, microbial and immunological factors, various new biological
      therapies targeting key mechanisms have emerged. In this review, a critical
      appraisal of modern therapeutical concepts will be presented, focusing on
      antibody and small inhibitory molecule therapies, including inhibition of TNF
      alpha and other pro-inflammatory cytokines, adhesion molecules and T cell
      activation, as well as hormonal therapies.

PMID- 15500401
TI  - Recent clinical development of dendritic cell-based immunotherapy for prostate
      cancer.
AB  - Dendritic cells (DCs) are the most powerful immune cells that present antigens to
      T cells, resulting in a T cell response. Therapeutic strategies involving DCs
      have been explored in many malignancies, including prostate cancer. These
      strategies are designed to stimulate DC proliferation, promote antigen uptake and
      processing by DCs, or to directly provide antigen-loaded DCs. All approaches are
      designed to stimulate an antitumour T cell response leading to clinical benefit.
      Many approaches in prostate cancer have demonstrated successful induction of the
      desired immune response. Clinical effect has also been observed, prompting larger
      definitive trials.

PMID- 15500402
TI  - Targeting dendritic cells with antigen-containing liposomes: antitumour immunity.
AB  - Dendritic cells (DCs) are antigen-presenting cells that play an important role in
      the body's immune defence against cancer. Strategies using antigen-primed DCs as
      tumour vaccines show promise in patients, but the approach is cumbersome to use
      clinically. Soluble tumour antigens can be targeted to DCs in vivo, but this
      often induces antigenic tolerance rather than immunity. Liposomes are vesicular
      lipid structures with adjuvant-like properties. Importantly, liposomes can
      encapsulate antigen and immunomodulatory factors, thus serving as potent delivery
      vehicles. Different strategies are being explored to target liposomal antigens to
      DCs in vivo. One approach has employed single-chain antibody fragments to the DC
      surface molecules CD11c and DEC-205, attached to the vesicle surface by metal
      chelating linkage, to target liposomal membranes containing antigen and either
      interferon-gamma or lipopolysaccharide to DCs. Such membranes induce dramatic
      antitumour responses and immunotherapeutic effects when used as a vaccine in the
      murine tumour model B16-OVA melanoma. Liposomal targeting of antigen and
      maturation signals directly to DCs in vivo, therefore, represents a much simpler
      strategy for cancer immunotherapy than antigen loading DCs ex vivo.

PMID- 15500403
TI  - Non-viral delivery of ribozymes for cancer gene therapy.
AB  - Ribozymes are RNA molecules with the capacity to effect sequence-specific
      cleavage of other transcripts. Since their initial discovery, there has been
      considerable interest in the development of ribozymes and other RNA therapeutics
      for gene therapy, particularly in the realm of cancer. However, as with other
      gene therapy applications, the delivery of ribozyme-based therapeutics to the
      target tissues of interest has represented a significant obstacle to the
      maturation of this technology to the clinical arena. This review will discuss the
      progress made so far in the use of non-viral methods for the systemic delivery of
      ribozymes for cancer gene therapy.

PMID- 15500404
TI  - Gene therapy strategies to improve the effectiveness of cancer radiotherapy.
AB  - Having the ability to alter the genetic makeup of a cancer cell by gene transfer
      is a potentially powerful strategy for treating human cancer. However, a low
      efficiency of gene delivery in vivo and poor tumour specificity has prevented the
      widespread implementation of this technology in the clinic. Despite these
      formidable obstacles, the first successful application of gene therapy in the
      treatment of cancer may occur when it is combined with local modalities such as
      radiation therapy. A small number of gene therapy strategies have been evaluated
      in clinical trials in combination with external beam radiation therapy. The
      combined therapy has been well-tolerated and has not exacerbated the side effects
      of radiation therapy. Gene transfer and tumour cell destruction has been
      demonstrated in vivo. Although the results await confirmation in larger,
      prospective Phase III trials, there is suggestive evidence that the combined
      therapies may be demonstrating better than expected antitumour activity. Our vast
      knowledge of the molecular defects that drive the cancer process, coupled with
      our expanding understanding of the genes responsible for tumour cell
      radioresistance, have spawned the development of rational, targeted gene
      therapies designed to increase tumour cell radiosensitivity. Here, the results of
      the clinical trials conducted so far will be reviewed, followed by a description
      of new approaches under development at present.

PMID- 15500405
TI  - The clinical potential of antiepileptic gene therapy.
AB  - Epilepsy afflicts approximately 1% of the population and, although the majority
      of patients gain effective seizure control through existing medications, a
      significant number prove refractory to treatment. For intractable focal
      epilepsies, gene therapy techniques provide a realistic treatment alternative,
      especially in patients who are considered surgical candidates. Neurotransmitter
      receptors and ion channels offer attractive gene therapy targets, but the pattern
      of viral vector transduction and gene expression can dramatically influence the
      final outcome. Recently, studies have shown that viral vector-mediated
      transduction and expression of neuroactive peptides, such as galanin and
      neuropeptide Y, can attenuate seizure sensitivity and prevent seizure-induced
      cell death in vivo. As future studies define the best means to avoid
      immunological silencing, as well as establish transduction properties in
      pathological, epileptic tissue, it should be possible to develop an efficacious
      gene therapy for intractable focal epilepsy.

PMID- 15500406
TI  - Antibody-directed enzyme prodrug therapy (ADEPT) for cancer.
AB  - Antibody-directed enzyme prodrug therapy (ADEPT) aims to restrict the cytotoxic
      action to tumour sites. The obstacles to achieve this were recognised at the
      outset, but time and experience have given these better definition. The
      development of fusion proteins has provided the means of making consistent
      antibody-enzyme constructs on an adequate scale, and glycosylation has provided
      the means to control the clearance of enzyme from non-tumour sites. Human enzymes
      have yet to be tested in a clinical setting, and there are pointers indicating
      that the immunological response to foreign enzymes can be overcome. The
      relatively small number of purpose-designed prodrugs tested so far leaves this an
      area ripe for further development. The ongoing iterative process between
      preclinical and clinical studies is critical to achieving the objective.

PMID- 15500407
TI  - Antigenic targets for renal cell carcinoma immunotherapy.
AB  - Renal cell carcinoma (RCC) has been shown to respond to immunotherapeutic
      intervention, thus fostering continued interest in exploiting the ability of the
      immune system to recognise and eradicate renal malignancy. Considerable progress
      in the characterisation of tumour-associated antigens, coupled with the
      appreciation that dendritic cells act as master regulators of immunity and
      tolerance, has opened new possibilities for immunotherapeutic intervention
      against human cancer. However, in contrast to other tumour systems, clinically
      relevant antigens expressed by RCC have not yet been identified. Therefore, most
      RCC vaccine trials have employed unfractionated antigens derived from tumour
      cells, with the goal of eliciting T cell responses against many unknown antigens
      expressed by the tumour. The recent discovery of genes with critical roles in
      oncogenesis has facilitated the identification of novel, more universal targets
      that may make cancer vaccines more practical, applicable and, potentially, more
      effective. In addition, immunisation against tumour antigens can be combined with
      tumour stroma-associated targets, thereby exerting a synergistic antitumour
      effect. Continued identification of molecular targets, in concert with more
      effective vaccination protocols, is likely to produce vaccination strategies with
      clinical impact.

PMID- 15500408
TI  - Vaccines against cervical cancer.
AB  - Cervical cancer and precancerous lesions of the genital tract are a major threat
      to women's health worldwide. Although the introduction of screening tests to
      detect cervical cancer and its precursor lesions has reduced overall cervical
      cancer rates in the developed world, the approach was largely unsuccessful for
      developing countries, primarily due to a lack of appropriate infrastructures and
      high costs. Annually, 470,000 cervical cancer cases are diagnosed worldwide, of
      which 80% occur in developing countries. Despite advances in treatment of
      cervical cancer, approximately half of the women afflicted with the disease will
      die. Over 20 years of dedicated research has provided conclusive evidence that a
      subset of human papillomaviruses are the aetiological agents for cervical cancer.
      Finding a viral origin for this disease provided the basis to fight cervical
      cancer using prophylactic or therapeutic vaccination. Both vaccine approaches are
      reviewed here, with an emphasis on recent clinical data.

PMID- 15500409
TI  - Biological therapy for the inner ear.
AB  - Biological therapy for the inner ear has the potential to revolutionise the
      treatment of sensorineural hearing loss, the most common form of deafness.
      Progress in the molecular understanding of hearing and hearing loss, combined
      with advances in the fields of both gene and cellular therapy for the inner ear,
      is providing a robust foundation from which clinical translation is plausible.
      Potential areas of interest in gene therapy and its preclinical application to
      deafness are reviewed, and experimental progress that has occurred in cellular
      therapy for the inner ear is examined.

PMID- 15500410
TI  - The selection of high-producing cell lines using flow cytometry and cell sorting.
AB  - The selection of high-producing cell lines is usually time-consuming and labour
      intensive. Following transfection, high-producing cells are selected using
      limiting dilution cloning to prevent non- and low-producing cells from outgrowing
      high-producing cells, a process that normally takes > 3 months. During this time,
      the cells have to be screened occasionally to ensure stability of the selected
      clone. Several new methods for selecting and screening cells using flow cytometry
      and cell sorting have recently been developed; these include gel microdrop
      technology, which encapsulates the cells in gelatine beads, and matrix-based
      secretion assays. This paper reviews these techniques for selecting high
      producing cell lines and isolating rare cells.

PMID- 15500411
TI  - Diclofenac-induced liver injury: a paradigm of idiosyncratic drug toxicity.
AB  - The advances in the drug development that allowed the replacement of many
      potentially hepatotoxic agents by safer alternatives have been out-weighed by the
      vast expansion of the total number of agents now available for use. Now, rare
      adverse reactions to several commonly prescribed medications contribute to the
      total burden of drug-induced liver injury. Studies involving well-characterised
      patients with diclofenac-induced hepatotoxicity indicate that multiple steps are
      involved in the development of liver injury. Individual susceptibility to
      idiosyncratic hepatotoxicity is determined by the interaction of metabolic and
      immunological factors. Immunomodulatory and anti-inflammatory cytokines, such as
      IL-10, may have a protective role in reducing drug-induced liver injury.
      Understanding the mechanisms of idiosyncratic hepatotoxicity may increase our
      ability to identify susceptible individuals and hence, prevent serious adverse
      reactions.

PMID- 15500412
TI  - The tolerability of riluzole in the treatment of patients with amyotrophic
      lateral sclerosis.
AB  - Riluzole is the only disease-modifying drug approved for the treatment of
      amyotrophic lateral sclerosis (ALS), in which it has been demonstrated to extend
      survival. The overall tolerability of riluzole is good and the drug can be used
      in all patients with ALS except those with elevated transaminase levels or active
      liver disease. The most frequently encountered adverse events (AEs) that appear
      to be attributed to riluzole are asthenia and nausea, observed in 18 and 15% of
      patients taking riluzole in the randomised clinical trial programme,
      respectively. These same AEs, albeit at a lower frequency, are also reported in
      Phase IV observational studies and in pharmacovigilance surveys. No unexpected AE
      clearly related to riluzole has emerged in the seven years that riluzole has been
      in extensive use in ALS patients. The most important potential safety issue with
      riluzole is hepatic impact with elevations of transaminases. Serum alanine
      aminotransferase levels more than three times the upper limit of normal are
      observed in 10 - 15% of patients. For this reason, strict monitoring of liver
      enzymes is recommended in patients with ALS taking riluzole, and treatment is
      contraindicated in subjects with elevated transaminases before the start of
      treatment. There is a suspicion that riluzole may, in rare cases, cause
      neutropenia, and physicians should be vigilant towards this risk.

PMID- 15500413
TI  - Chemotherapy-induced peripheral neurotoxicity.
AB  - Chemotherapy-induced peripheral neurotoxicity (CIPN) is a major clinical problem
      because it represents the dose-limiting side effects of a significant number of
      antineoplastic drugs. The incidence of CIPN varies depending on the drugs and
      schedules used, and this can be quite high, particularly when neurophysiological
      methods are used to make a diagnosis. However, even when CIPN is not a dose
      limiting side effect, its onset may severely affect the quality of life of cancer
      patients and cause chronic discomfort. In this review the features of CIPN due to
      the administration of the most widely used drugs, such as platinum drugs, taxanes
      and vinca alkaloids, and of two old drugs with new clinical applications, suramin
      and thalidomide, will be discussed. Moreover, the earliest data regarding the
      neurotoxicity of some new classes of very promising antineoplastic agents, such
      as epothilones and proteasome inhibitors, will be discussed. Finally, the data
      available on neuroprotectants, evaluated in the attempt to prevent CIPN, will be
      summarised.

PMID- 15500414
TI  - Rosuvastatin safety: lessons from the FDA review and post-approval surveillance.
AB  - Rosuvastatin is the first statin approved by the regulatory authorities since the
      withdrawal of cerivastatin. Although highly efficacious, this new statin has
      generated considerable controversy regarding its safety. Rosuvastatin was
      approved for clinical use based on the largest pre-approval database for all
      statins prior to commercial use. In this database, rosuvastatin had a similar
      safety profile to other approved statins up to the highest approval dose of 40
      mg. As with all statins, there is a marked increase in adverse effects when the
      dose is titrated from 40 to 80 mg, and rosuvastatin demonstrates a similar
      dose/toxicity relationship. In the pre-approval data trials on 80 mg, there was a
      1.0% (n = 16) incidence of myopathy and 7 patients developed rhabdomyolysis.
      However the <or= 40 mg doses had a myopathy rate similar to other statins. In the
      post-marketing surveillance for rosuvastatin, there have been reports of
      rhabdomyolysis, but the incidence rate, when corrected for prescription
      utilisation, is similar to other statins following initial approval.

PMID- 15500415
TI  - A benefit-risk assessment of class III antiarrhythmic agents.
AB  - The prevalence of arrhythmia in the population is increasing as more people
      survive for longer with cardiovascular disease. It was once thought that
      antiarrhythmic therapy could save life, however, it is now evident that
      antiarrhythmic therapy should be administrated with the purpose of symptomatic
      relief. Since many patients experience a decrease in physical performance as well
      as a diminished quality of life during arrhythmia there is still a need for
      antiarrhythmic drug therapy. The development of new antiarrhythmic agents has
      changed the focus from class I to class III agents since it became evident that
      with class I drug therapy the prevalence of mortality is considerably higher.
      This review focuses on the benefits and risks of known and newer class III
      antiarrhythmic agents. The benefits discussed include the ability to maintain
      sinus rhythm in persistent atrial fibrillation patients, and reducing the need
      for implantable cardioverter defibrillator shock/antitachycardia therapy, since
      no class III antiarrhythmic agents have proven survival benefit. The risks
      discussed mainly focus on pro-arrhythmia as torsade de pointes ventricular
      tachycardia.

PMID- 15500416
TI  - Mucocutaneous side effects of antineoplastic chemotherapy.
AB  - All structures of the skin may be affected by side effects of antineoplastic
      chemotherapy. The most commonly described effects concern skin adnexes,
      especially hair with alopecia. Nails are also frequently involved. Eccrine sweat
      or sebaceous gland involvement is more rarely reported. Mucous membranes,
      particularly in the mouth, are frequently altered by several mechanisms; direct
      cytotoxicity, infection, and a decrease in polymorphonuclear or platelet counts.
      Among cutaneous side effects, hyperpigmentation is very common and may have
      different clinical patterns; generalised, figurated, or localised. Acral erythema
      is another cutaneous side effect that is relatively specific to chemotherapy and
      is often dose-related. Some cutaneous side effects are related to an interaction
      between chemotherapy and radiation, particularly phototoxicity, recall
      phenomenon, and radiation enhancement. Miscellaneous, less frequent, side effects
      are described; sclerodermiform dermatitis, Raynaud's phenomenon, and
      hypersensitivity syndrome. In some cases, cutaneous side effects are relatively
      specific to one type of drug. Capillary leak syndrome is most often related to
      taxanes. Hydroxyurea is responsible for some peculiar cutaneous side effects
      (ulcerations, pseudo-dermatomyositis), perhaps due to long-term administration of
      the drug. Although mucocutaneous side effects of chemotherapy are frequent and
      sometimes severe, interruption of the culprit drug is rarely mandatory. However,
      adaptation of the dosage or prevention of some of these side effects remains
      necessary. Antineoplastic chemotherapies are widely used in many therapeutic
      protocols and may be responsible for numerous mucocutaneous side effects, either
      specific or more unusual. In rare cases, the severity of these side effects may
      require interruption of therapy. They may involve skin adnexes, mucous membranes
      or the skin itself. This review discusses cytotoxic antineoplastic drugs only,
      not cytokines, monoclonal antibodies or transduction factors used in the
      treatment of cancer.

PMID- 15500417
TI  - Arsenic trioxide in the treatment of haematological malignancies.
AB  - Arsenic trioxide (As(2)O(3)) for leukaemia treatment was described a century ago.
      Recent resurgence in the use of arsenic trioxide is related to its high efficacy
      in acute promyelocytic leukaemia (APL). Most arsenic trioxide preparations are
      intravenous, although an oral formulation is similarly efficacious. Side effects
      of arsenic trioxide are usually minor, including skin reactions, gastrointestinal
      upset, and reversible increases in transaminases. During therapy, a leukocytosis
      occasionally occurs, which may be complicated by fluid accumulation and pulmonary
      infiltration. Arsenic trioxide causes an asymptomatic QT prolongation in most
      patients. However, if concomitant cardiopulmonary diseases or electrolyte
      disturbances are present, more sinister arrhythmias may develop. Therefore,
      before commencement of arsenic trioxide therapy, a full cardiac assessment and
      avoidance of drugs that prolong QT interval should be instituted. Arsenic
      trioxide is partly renally excreted and, therefore, dose adjustment is required
      when renal function is impaired. In addition to its use in APL, arsenic trioxide
      is now tested in other malignancies, notably multiple myeloma.

PMID- 15500418
TI  - Risks of testosterone replacement therapy in ageing men.
AB  - Testosterone has been available to practitioners for several decades. However,
      testosterone prescriptions have increased in recent years partly because of the
      introduction of newer delivery systems that are topical and have good
      bioavailability. In the US alone, approximately 2 million prescriptions for
      testosterone were written in 2002. This represents a 30% increase from 2001 and a
      170% increase from 1999. There has also been a 500% increase in prescription
      sales in the past 10 years. The rise in prescriptions may be in part due to the
      increasing recognition of hypogonadism in ageing males or andropause. Treatment
      relating to hypogonadism has relieved symptoms and improved the quality of life
      of many individuals. Epidemiological studies point toward an association with
      increased morbidity and mortality, with low testosterone states in ageing males.
      For example, there is a higher prevalence of depression, coronary heart disease,
      osteoporosis, fracture rates, frailty and even dementia with low testosterone
      states. Recently, there have been some concerns raised regarding the long-term
      safety of testosterone replacement therapy (TRT) from the Institute of Medicine.
      Current evidence suggests no causal relationship between prostate cancer and
      physiological dosing of testosterone, especially with careful selection and
      monitoring of patients. Cardiovascular risks have, overall, been neutral,
      although suggestions have been made that there are positive vasodilatory
      properties with testosterone. Mild eythrocytosis can be a common side effect of
      TRT, but thromboembolic events have rarely been reported in the literature. This
      paper addresses the evidence to date regarding the safety aspects of TRT. The
      medical-legal implications of TRT for men at this point in time is also
      discussed.

PMID- 15500419
TI  - Disturbance of vision by COX-2 inhibitors.
AB  - In this review, 35 cases of acute, reversible, sometimes severe, disturbances of
      vision closely associated with the use of celecoxib or rofecoxib are described.
      These were identified from three different databases using strict selection
      criteria. The events included temporary blindness, visual field defect, scotoma,
      teichopsia, blurred vision, decreased vision and abnormal vision. The reactions
      had a mean onset time of 9.5 days and recovery occurred within 3 days following
      withdrawal of the drug. The reactions do not appear to be related to age, gender,
      dose, or indication for use. The incidence of reported cases is estimated to be
      not less than 5 per 10,000 patients. Possible mechanisms for this type of
      reaction are described. The most likely appears to be the result of interference
      with the retinal blood supply through reduced production of prostanoids. Genetic
      polymorphisms that affect drug metabolism or uptake could be risk factors and are
      discussed along with suggestions for research.

PMID- 15500420
TI  - The safety of black cohosh (Actaea racemosa, Cimicifuga racemosa).
AB  - Black cohosh (Actaea racemosa/Cimicifuga racemosa) is a North American perennial
      plant that has been used for traditional medicinal purposes by the native Indian
      population. Its modern day application is the treatment of menopausal symptoms.
      Unlike conventional non-herbal medications, herbal preparations have not been
      systematically evaluated for their safety. However, the evidence from in vitro,
      animal and clinical studies all suggest that black cohosh is a safe herbal
      therapy for menopausal women if taken for a limited period. More research is
      needed to evaluate the safety of this herb over longer periods of time, and also
      to further investigate its mechanism of action.

PMID- 15500421
TI  - Safety of drotrecogin alfa (activated) in the treatment of patients with severe
      sepsis.
AB  - While severe sepsis continues to plague hospitals worldwide, new treatment
      modalities, including activated recombinant protein C (drotrecogin alfa, Xigris,
      Lilly), have become a standard treatment alternative in many institutional
      algorithms. Drotrecogin alfa was shown to have a beneficial effect on mortality
      versus placebo in the PROWESS (Recombinant Human Activated Protein C Worldwide
      Evaluation in Severe Sepsis) trial (p = 0.005), but its use is not completely
      without risk. An increased risk of bleeding, including severe bleeding episodes,
      exists ranging 3.5 - 5.2% in the drotrecogin alfa treatment group versus 2.0 -
      5.0% in the placebo group. Patients at risk include those on concomitant heparin
      therapy (> 15,000 units/day), those with platelet counts <or= 30,000/mm(3), and
      those undergoing an invasive procedure during the scheduled infusion period.
      After almost three years on the US market, the reported incidence of severe
      bleeding episodes has risen only slightly from the pre-marketing era, at that
      time notable for restrictive treatment protocols, devoid of at-risk patients.
      Drotrecogin alfa, while a promising agent for severe sepsis, requires prudent
      patient evaluation for bleeding risks.

PMID- 15500422
TI  - Risk-benefit effects of tocolytic therapy.
AB  - Tocolytics are potent drugs that are used to interdict preterm labour. Although
      all of these agents have some side effects, if not frankly adverse effects under
      certain clinical situations, two of these drugs, the beta-mimetics and magnesium
      sulphate (MgSO(4)), have been found to have considerable potential for adverse
      maternal cardiovascular and respiratory effects. Furthermore, magnesium sulphate
      has been shown to have harmful, indeed, sometimes lethal, effects in some babies.
      Although less well established, NSAIDs, the most common example of which is
      indomethacin, also have some important adverse effects in fetuses. Within the
      limits of contemporary scientific knowledge, calcium channel blockers, such as
      nifedipine, appear to be among the more efficacious and safer drugs that are
      currently being used for tocolysis.

PMID- 15500423
TI  - Impact of phenytoin therapy on the skin and skin disease.
AB  - Phenytoin (diphenylhydantoin; Dilantin), ALZA Corp.) is a highly effective and
      widely prescribed anticonvulsant agent used in the treatment of focal and tonic
      clonic generalised seizures. The side effects of phenytoin can occassionally
      engender significant morbidity. Phenytoin can induce generalised eruptions that
      include: a maculopapular exanthem, Stevens-Johnson syndrome, generalised
      exfoliative dermatitis, toxic epidermal necrolysis, vasculitis and fixed drug
      eruptions. Phenytoin is linked to a hypersensitivity syndrome that manifests with
      fever, rash and lymphadenopathy. Patients receiving phenytoin may develop
      pseudolymphoma or, rarely, malignant lymphoma and mycosis fungoides-like lesions.
      Rarer cutaneous side effects include drug-induced lupus, purple hand syndrome,
      pigmentary alterations and IgA bullous dermatosis. Phenytoin can effect clotting
      function and alter vitamin and mineral levels. Prenatal exposure to phenytoin may
      result in a spectrum of structural, developmental and behavioural changes, known
      as the fetal hydantoin syndrome. Patients who use phenytoin in the long-term
      commonly manifest with gingival hyperplasia, coarsening of the facies, and
      hirsutism.

PMID- 15500424
TI  - Medicine or surgery for myocardial infarction: could facilitated angioplasty
      offer the best of both worlds?

PMID- 15500426
TI  - Nesiritide for the treatment of decompensated heart failure.
AB  - Heart failure is the leading cause of hospitalizations in the USA, and is
      associated with significant morbidity, mortality and resource utilization.
      Established therapies for chronic heart failure have been shown to improve
      outcomes, but treatment for decompensated heart failure remains largely empiric.
      Nesiritide (Natrecor) is a synthetic analog of human B-type natriuretic peptide,
      a peptide released by the ventricular myocardium in response to increased wall
      tension. The physiologic effects of human B-type natriuretic peptide include
      natriuresis, vasodilation and neurohormonal modulation. In clinical trials,
      nesiritide has been shown to decrease cardiac filling pressures, increase cardiac
      index, and improve the clinical status of patients with acute decompensated heart
      failure. Compared with other available intravenous agents for heart failure,
      nesiritide is effective, generally well-tolerated with few adverse effects, and
      does not require invasive monitoring during administration. Nesiritide has proven
      to be an effective new treatment for patients with decompensated heart failure.

PMID- 15500427
TI  - Role of manidipine in the management of patients with hypertension.
AB  - Manidipine is a third-generation dihydropyridine calcium antagonist, which causes
      systemic vasodilation by inhibiting the voltage-dependent calcium inward currents
      in smooth muscle cells. In clinical studies, manidipine has been shown to
      significantly lower office and 24-h blood pressure compared with placebo in
      patients with essential hypertension. The resulting reduction in blood pressure
      is maintained over 24 h, with preservation of the circadian blood pressure
      pattern; its blood pressure-lowering capacity appears to be similar to that of
      other calcium antagonists. In elderly patients with mild-to-moderate essential
      hypertension, manidipine is able to significantly decrease blood pressure
      compared with placebo for up to 3 years of treatment. The drug also significantly
      lowers blood pressure in patients with hypertension and concomitant Type 2
      diabetes mellitus or renal impairment, and is devoid of adverse metabolic
      effects. It is well-tolerated with few untoward adverse effects related to
      vasodilation. In particular, manidipine appears to have less potential for pedal
      edema than other calcium channel blockers.

PMID- 15500428
TI  - Candesartan cilexetil in cardiovascular disease.
AB  - Hypertension is a major cardiovascular risk factor, but most patients remain
      asymptomatic for many years. Successful therapy not only needs to be effective,
      it also needs to be well tolerated. Angiotensin receptor blockers have emerged as
      a major therapeutic class because they meet both of these requirements. Numerous
      studies indicate that all approved angiotensin receptor blockers are highly
      selective for angiotensin-1 receptors, lower blood pressure as monotherapies, and
      work well in combination with other drugs - particularly diuretics. The side
      effect profile of angiotensin receptor blockers is similar to that of placebo and
      they have not been associated with known side effects of angiotensin-converting
      enzyme inhibitors such as cough and angioneurotic edema. Candesartan cilexetil is
      an angiotensin receptor blocker with insurmountable binding properties to the
      angiotensin-1 receptor, long duration of action and improved efficacy. In
      patients with hypertension, candesartan monotherapy has been shown to be safe and
      effective. Comparative data have shown similar or better results to other
      monotherapies in blood-pressure control, and in combination with
      hydrochlorothiazide it has been shown to have additive or synergistic effects.
      More recent data demonstrate that candesartan cilexetil is useful in the
      treatment of patients with heart failure and may protect against diabetic
      nephropathy. Studies have also shown protection from stroke, particularly in
      patients with isolated systolic hypertension.

PMID- 15500429
TI  - Minimally invasive heart valve surgery: already established in clinical routine?
AB  - Cardiac valve replacement with the need for open heart surgery still has the
      highest morbidity and mortality rates among routine cardiac surgery, with the
      exception of aortic aneurysm repair and surgery for congenital heart defects.
      Reducing invasiveness is a desirable goal, and different strategies and
      approaches have been used to achieve this with valve repair or replacement less
      invasive. Despite the good results reported with minimally invasive techniques,
      time on extracorporal circulation is always longer compared with the conventional
      procedures. Since these techniques do not reduce real invasiveness but rather
      improve the cosmetic results, minimal-access surgery would be a better
      nomenclature. With the exception of patients at a high risk for sternal
      infections or redo heart operations, a reduction in postoperative morbidity by
      the avoidance of a median sternotomy is not yet definitely proven. Meanwhile,
      most surgeons comply with the demand for minimally invasive surgery posed by
      patients by reducing the length of the incision in aortic valve replacement and
      by using a right anterolateral approach with a limited incision for mitral valve
      operations. However, the use of endoscopic or robotic devices is limited to a few
      centers, and has not yet found its way into clinical routine. Nonetheless,
      minimally invasive or minimal-access surgery is now established in many centers,
      and patients should always be informed of these techniques. When this information
      is provided objectively and patient selection is carried out accurately, these
      alternative approaches can help to improve postoperative convalescence.

PMID- 15500430
TI  - Is it time for medical therapy for aortic valve disease?
AB  - Calcific aortic stenosis is the most common indication for surgical valve
      replacement. Currently there are no medical therapies approved for the treatment
      of this disease. This review will summarize the clinical and experimental studies
      published over the past 5 years that indicate that medical therapy may be an
      option for this patient population.

PMID- 15500431
TI  - Pharmacologic strategies for the prevention of atherosclerotic plaque
      progression.
AB  - Despite improved treatment options, coronary artery disease remains the leading
      cause of death in men and women in industrialized societies. Reduction of
      atherosclerotic disease will require the development and evaluation of new
      classes of pharmacologic agents capable of modifying the development and
      progression of the atherosclerotic disease process. The direct observation of
      coronary plaque burden and morphology with in vivo imaging modalities has been
      evaluated as an end point in serial pharmacologic intervention trials. This
      review will describe the use of intravascular ultrasound for such studies,
      summarize results from recent trials and outline potential future pharmacologic
      targets.

PMID- 15500432
TI  - Antihypertensive medications for risk reduction of first and recurrent ischemic
      stroke.
AB  - It is increasingly clear that even a small reduction in blood pressure results in
      a substantial risk reduction of vascular events including ischemic stroke.
      Recently, several comparative prospective trials of angiotensin-converting enzyme
      inhibitors and angiotensin-receptor blockers have demonstrated that, for
      equivalent reductions in blood pressure, these drugs may confer a greater effect
      on the prevention of primary and recurrent ischemic stroke compared with other
      antihypertensive medications. Given this information from prospective randomized
      trials, it appears that this class of drugs should be the first-line treatment
      for hypertension in patients at risk of a first or recurrent ischemic stroke.
      This review will critically assess the scientific basis and rationale of the use
      of angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers in
      primary and secondary stroke prevention.

PMID- 15500433
TI  - Recent advances in the secondary prevention of coronary heart disease.
AB  - Current practice guidelines provide recommendations for the secondary prevention
      of coronary heart disease. Following the publication of clinical trials in recent
      years, this review will highlight some controversial issues: the role of
      angiotensin and aldosterone antagonists after acute myocardial infarction; the
      effects of angiotensin-converting enzyme inhibitors in patients with stable
      coronary heart disease and preserved left ventricular ejection fraction; high
      intensity lowering of low-density lipoprotein cholesterol; use of 3-hydroxy-3
      methyl-glutaryl coenzyme A reductase inhibitors in the elderly; and the targeting
      of high-density lipoprotein cholesterol with niacin.

PMID- 15500434
TI  - AT1 receptor blockade for the prevention of cardiovascular events after
      myocardial infarction.
AB  - Myocardial infarction is associated with high morbidity and mortality. Multiple
      therapeutic modalities have been shown to be effective in reducing adverse
      postmyocardial infarction outcomes. The most prominent drugs that have been used
      in this group of patients are those that oppose the effects of the renin
      angiotensin-aldosterone system. These drugs include beta-blockers, angiotensin
      converting enzyme inhibitors, angiotensin receptor blockers and aldosterone
      blockers. Following initial success with angiotensin-converting enzyme inhibitors
      in reducing mortality and cardiac remodeling in postmyocardial infarction
      patients, recent focus has been on adjunctive or alternative use of angiotensin
      II-receptor antagonists. Multiple large-scale, randomized trials have been
      conducted in order to compare angiotensin II-receptor antagonists with a
      combination of angiotensin II-receptor antagonists and angiotensin-converting
      enzyme inhibitors, and with angiotensin-converting enzyme inhibitors alone in
      postmyocardial infarction patients and also in heart failure. Although some
      results are conflicting, the weight of evidence is towards equivalency of these
      two groups of medicines, provided that the maximum effective dose of the
      angiotensin II-receptor antagonists is used. The combination of an angiotensin
      converting enzyme inhibitor and an angiotensin II-receptor antagonist may have
      additional benefits for some, but not all, patients; for example, reducing
      morbidity and mortality in patients with chronic heart failure but not in
      postmyocardial infarction patients. Indeed, in the postmyocardial infarction
      setting, the combination appears simply to increase the side effects, without
      conferring additional benefits. Use of aldosterone antagonists as adjunctive
      therapy in postmyocardial infarction patients is associated with added benefits
      in terms of mortality reduction and will become the standard of care in this
      group of patients.

PMID- 15500435
TI  - Development of glycoprotein IIb-IIIa antagonists: translation of pharmacodynamic
      effects into clinical benefit.
AB  - This article will review the development of glycoprotein IIb-IIIa antagonists,
      with particular emphasis on the characteristics and pharmacodynamic studies of
      each agent that is available for clinical use. Abciximab is a Fab fragment of the
      7E3 antibody that has high affinity and a slow rate of dissociation from
      glycoprotein IIb-IIIa. In contrast, the small molecules eptifibatide and
      tirofiban, have a much more rapid rate of dissociation, with an off time of 10 to
      15 s. Accordingly, the circulating pool of abciximab is predominantly associated
      with platelets, whereas maintenance of a consistent concentration of tirofiban
      and eptifibatide in the blood is critical in order to achieve and sustain their
      inhibitory effects. The affinity of abciximab and tirofiban for glycoprotein IIb
      IIIa are substantially greater than that of eptifibatide, necessitating
      maintenance of greater molar concentrations of eptifibatide in blood in order to
      achieve effective inhibition of the binding of fibrinogen to the activated
      conformer of glycoprotein IIb-IIIa.

PMID- 15500436
TI  - Management of vasovagal syncope: 2004.
AB  - Vasovagal syncope is a common disorder that affects at least 20% of people at
      some time in their lives. Probably half of these patients faint recurrently; for
      many this causes physical trauma, a substantial reduction in quality of life, and
      difficulties with driving, employment and education. The last 15 years have seen
      striking advances in diagnostic approaches and prognostic understanding. A number
      of physiological, pharmacological and electrical therapies have been developed
      and tested to various degrees in patients. These include counterpressure
      manoeuvres, salt and fluid recommendations, and attempted treatment with
      fludrocortisone, midodrine, beta-blockers, serotonin reuptake inhibitors, and
      permanent pacemakers. This review highlights the most important of these advances
      and suggests strategies for managing this often difficult problem.

PMID- 15500437
TI  - Catheter ablation for atrial fibrillation: mechanism-based curative treatment.
AB  - The considerable cumulative morbidity and mortality burden resulting from atrial
      fibrillation has prompted renewed efforts to seek curative and widely applicable
      therapies. Currently used drugs are not only frequently ineffective at
      eliminating fibrillation, but may actually be life threatening. Extensive surgery
      involving both atria has shown that atrial fibrillation can be eliminated in
      most, if not all, patients, but at a significant cost. The recent discovery of
      the pivotal role that myocardial extensions into the pulmonary veins play in the
      initiation, and probably also the maintenance, of atrial fibrillation, has
      provided a relatively limited target conducive to catheter-based interventions.
      In experienced hands, paroxysmal atrial fibrillation can be eliminated in more
      than 85% of patients by a percutaneous intervention lasting less than 3 h with an
      attendant nonlethal complication risk of 1 to 2%. Thromboembolic complications
      and pulmonary vein stenosis are the principal complications that may result from
      this treatment, but their incidence is decreasing. Success rates in patients with
      persistent or permanent atrial fibrillation are lower, and it is anticipated that
      increased understanding of the underlying mechanisms will allow doctors to
      identify those subsets with the greatest potential for benefit from percutaneous
      catheter-based interventions. Such progress may allow doctors to extend the
      benefits of eliminating atrial fibrillation to the widest possible range of
      patients with this recalcitrant disorder.

PMID- 15500438
TI  - Hyperhomocysteinemia and the risk of restenosis after coronary artery stenting:
      fact or fiction?
AB  - The incidence of restenosis after coronary artery stent placement is
      approximately 38%. An interesting view has been stipulated: that
      hyperhomocysteinemia may be partly responsible for in-stent restenosis.
      Epidemiologic evidence exists that is persuasive in suggesting that individuals
      with occlusive vascular disease have a higher blood homocysteine concentration
      than control subjects. Thus, elevated plasma levels of homocysteine have been
      implicated as a risk factor for coronary artery disease. The composition of the
      current clinical knowledge on the question of whether hyperhomocysteinemia is a
      significant factor for restenosis of coronary artery stents consists of several
      trials with different approaches, objectives and outcomes. However, the current
      studies that have been published in the peer-reviewed medical literature have not
      reached a consensus as to whether an elevated plasma level of homocysteine is an
      independent risk factor responsible for restenosis following stent implantation.
      Our current knowledge as to the place of plasma homocysteine levels in the
      development of in-stent restenosis seems incomplete, and in the realm of
      homocysteine and restenosis of stents, there are plenty of questions that still
      remain to be answered.

PMID- 15500439
TI  - Distinct signalling particles containing ERK/MEK and B-Raf in PC12 cells.
AB  - Although several multiprotein complexes containing MAPKs (mitogen-activated
      protein kinases) have been identified using overexpression of kinases and
      scaffold proteins, the components of the complexes and their physical properties
      at endogenous expression levels have not been defined. We characterized a large
      protein complex containing a nerve-growth-factor-activated ERK (extracellular
      signal-regulated kinase) and MEK (MAPK/ERK kinase) in rat pheochromocytoma (PC12)
      cells. This protein complex fractionated into a high-speed pellet and was
      resistant to non-ionic detergent treatments that solubilized membranes.
      Disruption of protein-protein interactions by treatment with high salt was
      required to facilitate immunoprecipitation of active ERK1 and co-precipitation of
      MEK1. Microtubule fragments were also present in the detergent-resistant high
      speed pellet, and some kinases were bound to them, especially ERK1b (an
      alternatively spliced isoform of ERK1), which showed a strong preference for
      binding microtubules. The large protein complex containing ERK1 and MEK1 was
      resolved by velocity sedimentation from fragments of microtubules; however, it
      did not contain other scaffolding components known to bind ERK and MEK. B-Raf was
      also present in a distinct detergent-resistant, microtubule-independent protein
      complex slightly larger than that containing ERK and MEK. We conclude that there
      are two independent nerve growth factor-regulated 'signalling particles' with an
      estimated size of 60-75 S, one containing ERK1 and MEK1 and the other containing
      B-Raf. These signalling particles may have a role in the temporal and spatial
      regulation of kinase activity inside cells.

PMID- 15500440
TI  - Maturation of the unusual single-cysteine (XXXCH) mitochondrial c-type
      cytochromes found in trypanosomatids must occur through a novel biogenesis
      pathway.
AB  - The c-type cytochromes are characterized by the covalent attachment of haem to
      the polypeptide via thioether bonds formed from haem vinyl groups and, normally,
      the thiols of two cysteines in a CXXCH motif. Intriguingly, the mitochondrial
      cytochromes c and c1 from two euglenids and the Trypanosomatidae contain only a
      single cysteine within the haem-binding motif (XXXCH). There are three known
      distinct pathways by which c-type cytochromes are matured post-translationally in
      different organisms. The absence of genes encoding any of these c-type cytochrome
      biogenesis machineries is established here by analysis of six trypanosomatid
      genomes, and correlates with the presence of single-cysteine cytochromes c and
      c1. In contrast, we have identified a comprehensive catalogue of proteins
      required for a typical mitochondrial oxidative phosphorylation apparatus. Neither
      spontaneous nor catalysed maturation of the single-cysteine Trypanosoma brucei
      cytochrome c occurred in Escherichia coli. However, a CXXCH variant was matured
      by the E. coli cytochrome c maturation machinery, confirming the proposed
      requirement of the latter for two cysteines in the haem-binding motif and
      indicating that T. brucei cytochrome c can accommodate a second cysteine in a
      CXXCH motif. The single-cysteine haem attachment conserved in cytochromes c and
      c1 of the trypanosomatids is suggested to be related to their cytochrome c
      maturation machinery, and the environment in the mitochondrial intermembrane
      space. Our genomic and biochemical studies provide very persuasive evidence that
      the trypanosomatid mitochondrial cytochromes c are matured by a novel biogenesis
      system.

PMID- 15500441
TI  - Purification and biochemical characterization of native ERp29 from rat liver.
AB  - ERp29 is a recently characterized resident of the ER (endoplasmic reticulum)
      lumen that has broad biological significance, being expressed ubiquitously and
      abundantly in animal cells. As an apparent housekeeper, ERp29 is thought to be a
      general folding assistant for secretory proteins and to probably function as a
      PDI (protein disulphide isomerase)-like molecular chaperone. In the present
      paper, we report the first purification to homogeneity and direct functional
      analysis of native ERp29, which has led to the unexpected finding that ERp29
      lacks PDI-like folding activities. ERp29 was purified 4800-fold in non-denaturing
      conditions exploiting an unusual affinity for heparin. Two additional biochemical
      hallmarks that will assist the classification of ERp29 homologues were
      identified, namely the idiosyncratic behaviours of ERp29 on size-exclusion
      chromatography (M(r)<globular homodimer) and SDS/PAGE (M(r)>monomeric mass). In
      contrast with PDI and parallel-purified co-residents (calreticulin, ERp60),
      native ERp29 lacked classical chaperone, disulphide reductase and isomerase, and
      calcium-binding activities. In the chaperone assays, ERp29 neither protected
      substrate proteins against thermal aggregation nor interacted stably with
      chemically denatured proteins as detected by cross-linking. ERp29 also did not
      exhibit helper activity toward calreticulin (chaperone) or PDI and ERp60
      (disulphide reductase). By refuting long-standing predictions about chaperone
      activity, these results expose ERp29 as a functionally distinct member of the ER
      machinery and prompt a revised hypothesis that ERp29 acts as a non-classical
      folding assistant. The native preparation and biochemical hallmarks established
      here provide a useful foundation for ongoing efforts to resolve the functional
      orphan status of ERp29.

PMID- 15500442
TI  - Pro-apoptotic Bid induces membrane perturbation by inserting selected lysolipids
      into the bilayer.
AB  - Bid is a BH3-only member of the Bcl-2 family that regulates cell death at the
      level of mitochondrial membranes. Bid appears to link the mitochondrial pathway
      with the death receptor-mediated pathway of cell death. It is generally assumed
      that the f.l. (full-length) protein becomes activated after proteolytic cleavage,
      especially by apical caspases like caspase 8. The cleaved protein then relocates
      to mitochondria and promotes membrane permeabilization, presumably by interaction
      with mitochondrial lipids and other Bcl-2 proteins that facilitate the release of
      apoptogenic proteins like cytochrome c. Although the major action may reside in
      the C-terminus part, tBid (cleaved Bid), un-cleaved Bid also has pro-apoptotic
      potential when ectopically expressed in cells or in vitro. This pro-apoptotic
      action of f.l. Bid has remained unexplained, especially at the biochemical level.
      In the present study, we show that f.l. (full-length) Bid can insert specific
      lysolipids into the membrane surface, thereby priming mitochondria for the
      release of apoptogenic factors. This is most effective for
      lysophosphatidylcholine species that we report to accumulate in mitochondria
      during apoptosis induction. A Bid mutant that is not pro-apoptotic in vivo is
      defective in lysophosphatidylcholine-mediated membrane perturbation in vitro. Our
      results thus provide a biochemical explanation for the pro-apoptotic action of
      f.l. Bid.

PMID- 15500443
TI  - Structure-based mutagenesis studies of the peptide substrate binding fragment of
      type I heat-shock protein 40.
AB  - Ydj1 is the major type I Hsp40 (heat-shock protein 40) family member in yeast.
      Ydj1 can pair with yeast Hsp70 Ssa1 to facilitate protein translocation and
      protein folding. Ydj1 itself can also function as a molecular chaperone to bind
      the non-native polypeptides and suppress protein aggregations in vitro. The
      crystal structure of Ydj1 complexed with its peptide substrate GWLYEIS reveals
      that a hydrophobic pocket located on Ydj1 domain I may play a major role in
      mediating the interactions between Ydj1 and the peptide substrate. To understand
      the mechanism by which Ydj1 interacts with non-native polypeptide, we have
      mutated the residues forming the hydrophobic pocket, based on the structural
      information. We have also constructed deletion mutations of the zinc-finger
      motifs within Ydj1. We have examined the functional consequences of these Ydj1
      mutants by in vivo and in vitro assays. The results indicated that the
      hydrophobic pocket located on Ydj1 plays a critical role in its molecular
      chaperone activity by mediating interactions with the non-native polypeptides.

PMID- 15500445
TI  - Analysis of normal and mutant iduronate-2-sulphatase conformation.
AB  - Mammalian sulphatases (EC 3.1.6) are a family of enzymes that have a high degree
      of similarity in amino acid sequence, structure and catalytic mechanism. IDS
      (iduronate-2-sulphatase; EC 3.1.6.13) is a lysosomal exo-sulphatase that belongs
      to this protein family and is involved in the degradation of the
      glycosaminoglycans heparan sulphate and dermatan sulphate. An IDS deficiency
      causes the lysosomal storage disorder MPS II (mucopolysaccharidosis type II). To
      examine the structural alterations in heat-denatured and mutant IDS, a panel of
      four monoclonal antibodies was raised to the denatured protein and used as probes
      of protein conformation. The linear sequence epitope reactivity of a polyclonal
      antibody raised against the native protein and the monoclonal antibodies were
      defined and mapped to distinct regions on the IDS protein. The antigenicity of
      native IDS was higher in regions without glycosylation, but reactivity was not
      restricted to protein surface epitopes. One monoclonal epitope was relatively
      surface accessible and in close proximity to an N-linked glycosylation site,
      while three others required additional thermal energy to expose the epitopes. The
      monoclonal antibodies demonstrated the capacity to differentiate progressive
      structural changes in IDS and could be used to characterize the severity of MPS
      type II in patients based on variable denatured microstates.

PMID- 15500444
TI  - CLOCK is involved in the circadian transactivation of peroxisome-proliferator
      activated receptor alpha (PPARalpha) in mice.
AB  - PPARalpha (peroxisome-proliferator-activated receptor alpha) is a member of the
      nuclear receptor superfamily of ligand-activated transcription factors that
      regulate the expression of genes associated with lipid metabolism. In the present
      study, we show that circadian expression of mouse PPARalpha mRNA requires the
      basic helix-loop-helix PAS (Per-Arnt-Sim) protein CLOCK, a core component of the
      negative-feedback loop that drives circadian oscillators in mammals. The
      circadian expression of PPARalpha mRNA was abolished in the liver of homozygous
      Clock mutant mice. Using wild-type and Clock-deficient fibroblasts derived from
      homozygous Clock mutant mice, we showed that the circadian expression of
      PPARalpha mRNA is regulated by the peripheral oscillators in a CLOCK-dependent
      manner. Transient transfection and EMSAs (electrophoretic mobility-shift assays)
      revealed that the CLOCK-BMAL1 (brain and muscle Arnt-like protein 1) heterodimer
      transactivates the PPARalpha gene via an E-box-rich region located in the second
      intron. This region contained two perfect E-boxes and four E-box-like motifs
      within 90 bases. ChIP (chromatin immunoprecipitation) also showed that CLOCK
      associates with this E-box-rich region in vivo. Circadian expression of PPARalpha
      mRNA was intact in the liver of insulin-dependent diabetic and of
      adrenalectomized mice, suggesting that endogenous insulin and glucocorticoids are
      not essential for the rhythmic expression of the PPARalpha gene. These results
      suggested that CLOCK plays an important role in lipid homoeostasis by regulating
      the transcription of a key protein, PPARalpha.

PMID- 15500446
TI  - Subtype-specific regulation of equilibrative nucleoside transporters by protein
      kinase CK2.
AB  - Two subtypes of equilibrative transporters, es (equilibrative inhibitor
      sensitive) and ei (equilibrative inhibitor-insensitive), are responsible for the
      majority of nucleoside flux across mammalian cell membranes. Sequence analyses of
      the representative genes, ENT1 {equilibrative nucleoside transporter 1; also
      known as SLC29A1 [solute carrier family 29 (nucleoside transporters), member 1]}
      and ENT2 (SLC29A2), suggest that protein kinase CK2-mediated phosphorylation may
      be involved in the regulation of es- and ei-mediated nucleoside transport. We
      used human osteosarcoma cells transfected with catalytically active or inactive
      alpha' and alpha subunits of CK2 to assess the effects of CK2 manipulation on
      nucleoside transport activity. Expression of inactive CK2alpha' (decreased
      CK2alpha' activity) increased the number of binding sites (approximately 1.5
      fold) for the es-specific probe [3H]NBMPR ([3H]nitrobenzylthioinosine), and
      increased (approximately 1.8-fold) the V(max) for 2-chloro[3H]adenosine of the
      NBMPR-sensitive (es) nucleoside transporter. There was a concomitant decrease in
      the V(max) of the NBMPR-resistant (ei-mediated) uptake of 2-chloro[3H]adenosine.
      This inhibition of CK2alpha' activity had no effect, however, on either the K(D)
      of [3H]NBMPR binding or the K(m) of 2-chloro[3H]adenosine uptake. Quantitative
      PCR showed a transient decrease in the expression of both hENT1 (human ENT1) and
      hENT2 mRNAs within 4-12 h of induction of the inactive CK2alpha' subunit, but
      both transcripts had returned to control levels by 24 h. These data suggest that
      inhibition of CK2alpha' reduced ei activity by attenuation of hENT2
      transcription, while the increase in es/hENT1 activity was mediated by post
      translational action of CK2. The observed modification in es activity was
      probably due to a CK2alpha'-mediated change in the phosphorylation state of the
      ENT1 protein, or an interacting protein, effecting an increase in the plasma
      membrane lifetime of the transport proteins.

PMID- 15500447
TI  - Proteolytic processing and glycosylation influence formation of porcine prion
      protein complexes.
AB  - High level of heterogeneity seems to be a ubiquitous feature of mammalian PrPs
      (prion proteins) and may be relevant to the pathogenesis of prion diseases. In
      the present study, we describe the heterogeneity of PrP(C) (cellular form of PrP)
      from porcine brain. It was disclosed and characterized by a combination of one
      dimensional PAGE and two-dimensional PAGE analyses with enzymic deglycosylation
      and copper-affinity experiments. We found that the identified two main
      populations of porcine PrP(C) consist of diglycosylated forms and correspond to
      the full-length (molecular mass 32-36 kDa) and proteolytically modified protein
      (molecular mass 25-30 kDa), known as C1. The two populations were fully separated
      during Cu2+-loaded immobilized metal affinity chromatography, indicating
      different affinity for copper ions. The more basic forms, migrating as species of
      higher molecular mass, exhibited stronger affinity for copper ions, whereas those
      with more acidic pI and of lower molecular mass were low-affinity Cu2+-binding
      molecules and thus could represent N-terminally truncated PrP(C). Size-exclusion
      chromatography revealed that most of the PrP(C) molecules in porcine brain
      extracts exist in the form of high-molecular-mass complexes (probably with other
      proteins). The heterogeneity of porcine PrP(C), resulting from proteolytic
      modification and glycosylation, influences its ability to assemble into these
      complexes. N-truncated molecules dominate over full-length PrP(C) in fractions of
      molecular mass over the range 65-130 kDa, whereas the full-length species are the
      major forms of PrP(C) present in the monomeric fraction and in complexes above
      130 kDa. Two-dimensional PAGE analysis indicated that the complexed PrP(C)
      differs in the composition of pI forms from the monomers.

PMID- 15500448
TI  - Depletion of Caco-2 cell cholesterol disrupts barrier function by altering the
      detergent solubility and distribution of specific tight-junction proteins.
AB  - In the present study, we have investigated the role of cholesterol in maintaining
      the barrier properties of the model intestinal cell line Caco-2. We have
      extracted membrane cholesterol using methyl-beta-cyclodextrin and demonstrated
      that maximally, methyl-beta-cyclodextrin lowered cell cholesterol levels by 40
      45%. Depletion of cell cholesterol was accompanied by an 80-90% decrease in
      monolayer transepithelial electrical resistance and a significant increase in the
      paracellular permeability of dextrans of 4, 10 and 40 kDa. The increase in
      dextran permeability was most pronounced for the two lower molecular mass
      species. In addition to the decline in the barrier properties of the monolayers,
      extraction of cell cholesterol produced an increase in the Triton X-100
      solubility of claudin 3, claudin 4 and occludin, and the loss of all three
      proteins from the plasma membrane (tight junctions). In contrast, removal of
      cholesterol had no detectable influence on the detergent solubility or
      morphological distribution of claudin 1. These results indicate that membrane
      cholesterol is a critical factor in maintaining the barrier property of
      epithelial monolayers. More specifically, cholesterol appears to stabilize the
      association of certain proteins with the tight junctions.

PMID- 15500449
TI  - Characterization of phylogenetically distant members of the adenylate cyclase
      family from mycobacteria: Rv1647 from Mycobacterium tuberculosis and its
      orthologue ML1399 from M. leprae.
AB  - Analysis of the genome sequence of Mycobacterium tuberculosis H37Rv has
      identified 16 genes that are similar to the mammalian adenylate and guanylate
      cyclases. Rv1647 was predicted to be an active adenylate cyclase but its position
      in a phylogenetically distant branch from the other enzymes characterized so far
      from M. tuberculosis makes it an interestingly divergent nucleotide cyclase to
      study. In agreement with its divergence at the sequence level from other
      nucleotide cyclases, the cloning, expression and purification of Rv1647 revealed
      differences in its biochemical properties from the previously characterized
      Rv1625c adenylate cyclase. Adenylate cyclase activity of Rv1647 was activated by
      detergents but was resistant to high concentrations of salt. Mutations of
      substrate-specifying residues to those present in guanylate cyclases failed to
      convert the enzyme into a guanylate cyclase, and did not alter its oligomeric
      status. Orthologues of Rv1647 could be found in M. leprae, M. avium and M.
      smegmatis. The orthologue from M. leprae (ML1399) was cloned, and the protein was
      expressed, purified and shown biochemically to be an adenylate cyclase, thus
      representing the first adenylate cyclase to be described from M. leprae.
      Importantly, Western-blot analysis of subcellular fractions from M. tuberculosis
      and M. leprae revealed that the Rv1647 and ML1399 gene products respectively were
      expressed in these bacteria. Additionally, M. tuberculosis was also found to
      express the Rv1625c adenylate cyclase, suggesting that multiple adenylate cyclase
      proteins may be expressed simultaneously in this organism. These results suggest
      that class III cyclase-like gene products probably have an important role to play
      in the physiology and perhaps the pathology of these medically important
      bacteria.

PMID- 15500451
TI  - Reaction rates in allogeneic donors.
AB  - In Canada and several other countries, there is an upper age limit for blood
      donation. In order to evaluate the safety of whole blood donation in elderly
      Canadian allogeneic donors, we analysed reaction rates following whole blood
      donation. Reactions rates in allogeneic whole blood donors who donated at
      Canadian Blood Services were reviewed retrospectively. Rates were analysed by
      age, donation frequency and by donation frequency for each age group. A total of
      5478 reactions were available for analysis in 469 837 donors. The highest rate of
      mild reactions occurred in donors less than 20 years of age. Moderate and severe
      reactions decreased with increasing age and with donation frequency. Age-adjusted
      rates for mild reactions were less frequent in donors aged 66-77 years than in
      donors younger than 20 years. Although age-adjusted moderate reactions varied
      with donation frequency, after seven donations, rates were not increased for
      donors aged 60 years or older (0.61% for donors aged less than 20 years compared
      to 0.03% for donors aged 60-65 years compared to 0% for donors aged 66-71 years).
      Age-adjusted rates for severe reactions generally did not increase with donation
      frequency. These results confirm the safety of whole blood donation in regular
      donors who are 66-71 years of age.

PMID- 15500450
TI  - Compound heterozygosity for mutations Asp611-->Tyr in KCNQ1 and Asp609-->Gly in
      KCNH2 associated with severe long QT syndrome.
AB  - LQTS (long QT syndrome) is an inherited cardiac disorder characterized by
      prolongation of QT interval, torsades de pointes and sudden death. We have
      identified two heterozygous missense mutations in the KCNQ1 and KCNH2 (also known
      as HERG) genes [Asp611-->Tyr (D611Y) in KCNQ1 and Asp609-->Gly (D609G) in KCNH2]
      in a 2-year-old boy with LQTS. The aim of the present study was to characterize
      the contributions of the mutations in the KCNQ1 and KCNH2 genes relative to the
      clinical manifestations and electrophysiological properties of LQTS. Six of 11
      carriers of D611Y in KCNQ1 had long QT intervals. D609G in KCNH2 was detected
      only in the proband. Studies on the electrophysiological alterations due to the
      two missense mutations revealed that the D611Y mutation in KCNQ1 did not show a
      significant suppression of the currents compared with wild-type, but the time
      constants of current activation in the mutants were increased compared with that
      in the wild-type. In contrast, the D609G mutation in KCNH2 showed a dominant
      negative suppression. Our results suggest that the mild phenotype produced by the
      D611Y mutation in KCNQ1 became more serious by addition of the D609G mutation in
      KCNH2 in the proband.

PMID- 15500452
TI  - A survey of autologous blood transfusion practices in Germany.
AB  - This survey was designed to evaluate the use of autologous blood transfusion
      techniques in Germany in 2000 and to identify how the use of these techniques has
      changed over the past 5 years. Questionnaires were mailed to the chief
      anaesthesiologists of 400 randomly selected German hospitals with > or =25
      surgical beds. Information was sought about the current and past use of
      preoperative autologous blood donation (PABD), acute preoperative haemodilution
      and peri-operative blood salvage. Data were requested for the calendar year 2000.
      Three hundred and forty-three (86%) completed questionnaires were returned. PABD,
      haemodilution and peri-operative blood salvage were used by 85, 54 and 67% of
      respondents, respectively. Thirty-seven per cent of PABD users reported that PABD
      use declined, 28% reported that it increased and 34% reported that it remained
      unchanged over the past 5 years. The proportions of those reporting declining vs.
      increasing use of PABD did not differ significantly (P = 0.09). Sixty per cent of
      users of haemodilution reported that its use declined, 10% reported that it
      increased and 29% reported that it remained unchanged over the past 5 years.
      Sixteen per cent of hospitals that were equipped with cell-washing devices
      reported that the use of these devices declined, 47% reported that it increased
      and 37% reported that it remained unchanged over the past 5 years. The results
      indicate that autologous blood transfusion techniques were widely used in Germany
      in 2000, with PABD being the most common technique. The use of PABD did not
      change significantly, the use of haemodilution declined markedly and the use of
      peri-operative cell salvage increased markedly during the past 5 years before the
      survey.

PMID- 15500453
TI  - Is routine post-operative haemoglobin measurement required after transurethral
      resection of the prostate?
AB  - The aim of this study is to evaluate the rate of blood transfusion during the
      post-operative period in patients undergoing transurethral resection of the
      prostate (TURP) and to determine the value of using post-operative haemoglobin
      (Hb) measurement as a guide to transfusion requirements. In a retrospective
      study, pre- and post-operative Hb measurements and the resected prostatic tissue
      weights were recorded for 106 patients. There was a statistically significant
      change in the Hb concentration within 48 h of the operation (P < 0.0001),
      although this was clinically insignificant in the majority of patients. The post
      operative blood transfusion rate was 0.85% and there was a significant
      correlation between change in Hb concentration and the resected tissue weight (P
      < 0.0001). Our results show that routine post-operative Hb is not necessary in
      patients following a TURP.

PMID- 15500454
TI  - Safety and efficacy of unmodified whole blood vs. buffy coat-depleted red cell
      concentrates in autologous transfusion of elective orthopaedic surgery patients.
AB  - Storing autologous blood as whole blood (WB) has been proposed for increasing the
      cost-effectiveness of preoperative autologous blood donation programmes. However,
      experimental data suggest that autologous leucocytes might lead to
      immunomodulation similar to the effect attributed to allogeneic leucocytes. In a
      retrospective analysis, the postoperative outcome of 120 patients undergoing
      elective orthopaedic surgery and having donated up to two units of autologous WB
      (AWB) was compared with that of a control group of 52 patients, whose autologous
      donation had been processed into buffy coat-depleted red cell concentrates (RCC).
      At least one autologous unit, but no allogeneic units, had been transfused in all
      analysed patients. Donation schemes were equally efficacious in both groups.
      There was no significant difference in postoperative infection rates between the
      two groups. Overall rates were 7.7% in the RCC group and 8.3% in the WB group.
      Surgical, thromboembolic and other recorded complications, length of
      postoperative hospital stay and days of the use of antibiotics were also not
      significantly different between the two groups. The results of this study suggest
      that transfusion of up to two units of unmodified AWB is as efficacious as the
      transfusion of autologous RCC and does not negatively influence the postoperative
      outcome in elective orthopaedic surgery.

PMID- 15500455
TI  - Activation of polymorphonuclear neutrophils by immune complex: possible
      involvement in development of transfusion-related acute lung injury.
AB  - Transfusion-related acute lung injury (TRALI) is a serious side-effect of
      transfusion. We presumed that immune complex (IC)-activated polymorphonuclear
      neutrophils (PMNs) are involved in the development of TRALI. The aim of this
      study is to examine the various effects of ICs on normal human PMNs. ICs used
      here were artificially formed by combining soluble human leucocyte antigen (HLA)
      class II-positive serum and anti-HLA class II antiserum. The abilities of ICs to
      trigger PMNs and induce the production of soluble mediators and the involvement
      of the Fc receptor (FcR) in the activation of PMNs by ICs were investigated.
      Moreover, the ability of the culture supernatant of PMNs incubated with ICs
      regarded to induce the apoptosis of lung microvascular endothelial (LME) cells
      was examined. The results proved that PMNs are triggered by ICs resulting in the
      acceleration of the production of tumour necrosis factor-alpha (TNF-alpha),
      perforin and Fas ligand, in which FcR on PMNs appears to be involved.
      Furthermore, the culture supernatants of PMNs cultured with ICs were revealed to
      induce the apoptosis of LME cells. In conclusion, the ICs used here were proved
      to induce PMNs to release cytotoxic factors upon activation. These results
      suggest that ICs are mediators of the development of TRALI.

PMID- 15500456
TI  - Cryoprecipitate prepared from plasma treated with methylene blue plus light:
      increasing the fibrinogen concentration.
AB  - When cryoprecipitate is prepared from plasma which has been treated with
      methylene blue plus light (MB) for the purpose of virus inactivation, clottable
      fibrinogen content is 40% lower compared with units prepared from untreated
      plasma. Initial studies showed that when frozen MB plasma units were removed to
      +2 to +6 degrees C for 4 h and then returned to -40 degrees C prior to
      cryoprecipitation, fibrinogen recoveries increased from 24 to 42%. Although
      fibrinogen yield improved when plasma units were stored at +2 to +6 degrees C for
      varying lengths of time, FVIII levels decreased with increasing time.
      Conditioning for 8 h was studied in more detail. Groups of two plasma units were
      mixed together, divided into two equal units, frozen/thawed and treated with MB.
      One of each pair was stored continually at -40 degrees C, whereas the other was
      removed to +2 to +6 degrees C for 8 h. Samples were assayed for fibrinogen,
      FVIII, VWF:Ristocetin cofactor activity (RCo), VWF:Ag and VWF:Collagen binding
      (CB). The cryoprecipitate fibrinogen content increased to a mean of 207 mg unit(
      1). VWF:Ag, VWF:RCo and VWF:CB recoveries also increased. FVIII recovery
      decreased from 50 to 45% (mean 124 iu unit(-1)). Conditioning has been validated
      for routine production of cryoprecipitate from imported plasma.

PMID- 15500457
TI  - Hypotension and acute pulmonary insufficiency following transfusion of autologous
      red blood cells during surgery: a case report and review of the literature.
AB  - Transfusion of autologous blood is associated with fewer complications, although
      all untoward events of transfusion may not be negated with this strategy. We
      report a case of acute pulmonary insufficiency and hypotension following
      transfusion of autologous packed red blood cells (PRBCs) in a patient, who was
      undergoing major surgery. Anti-HLA class-I and class-II and anti-granulocyte
      antibodies were measured in the unit and in the recipient. Neutrophil (PMN)
      priming activity was measured as the augmentation of the formyl-Met-Leu-Phe
      activated respiratory burst. No immunoglobulins were identified; however,
      significant lipid-priming activity was present in the implicated, autologous PRBC
      unit that primed PMNs from both healthy people and the recipient. In addition,
      lipids, identical to those that accumulate during PRBC storage, caused
      significant hypotension when infused into rats at similar concentrations found in
      stored PRBCs. We conclude that the observed transfusion-related acute lung injury
      reaction with significant hypotension may be the result of two independent
      events: the first is related to inherent host factors, in this case major
      surgery, and the second is the infusion of lipids that accumulate during the
      routine storage of PRBCs.

PMID- 15500458
TI  - NAT testing for HBV: the first routine application in Italy.

PMID- 15500459
TI  - Red cell freezing and its impact on the supply chain.

PMID- 15500462
TI  - Folate synthesis in plants: the last step of the p-aminobenzoate branch is
      catalyzed by a plastidial aminodeoxychorismate lyase.
AB  - In plants, the last step in the synthesis of p-aminobenzoate (PABA) moiety of
      folate remains to be elucidated. In Escherichia coli, this step is catalyzed by
      the PabC protein, a beta-lyase that converts 4-amino-4-deoxychorismate (ADC)--the
      reaction product of the PabA and PabB enzymes--to PABA and pyruvate. So far, the
      only known plant enzyme involved in PABA synthesis is ADC synthase, which has
      fused domains homologous to E. coli PabA and PabB and is located in plastids. ADC
      synthase has no lyase activity, implying that plants have a separate ADC lyase.
      No such lyase is known in any eukaryote. Genomic and phylogenetic approaches
      identified Arabidopsis and tomato cDNAs encoding PabC homologs with putative
      chloroplast-targeting peptides. These cDNAs were shown to encode functional
      enzymes by complementation of an E. coli pabC mutant, and by demonstrating that
      the partially purified recombinant proteins convert ADC to PABA. Plant ADC lyase
      is active as dimer and is not feedback inhibited by physiologic concentrations of
      PABA, its glucose ester, or folates. The full-length Arabidopsis ADC lyase
      polypeptide was translocated into isolated pea chloroplasts and, when fused to
      green fluorescent protein, directed the passenger protein to Arabidopsis
      chloroplasts in transient expression experiments. These data indicate that ADC
      lyase, like ADC synthase, is present in plastids. As shown previously for the ADC
      synthase transcript, the level of ADC lyase mRNA in the pericarp of tomato fruit
      falls sharply as ripening advances, suggesting that the expression of these two
      enzymes is coregulated.

PMID- 15500463
TI  - The NAC domain mediates functional specificity of CUP-SHAPED COTYLEDON proteins.
AB  - In higher plants, although several genes involved in shoot apical meristem (SAM)
      formation and organ separation have been isolated, the molecular mechanisms by
      which they function are largely unknown. CUP-SHAPED COTYLEDON (CUC) 1 and CUC2
      are examples of two such genes that encode the NAC domain proteins. This study
      investigated the molecular basis for their activities. Nuclear localization
      assays indicated that green fluorescent protein (GFP)-CUC proteins accumulate in
      the nucleus. Yeast one-hybrid and transient expression assays demonstrated that
      the C-terminal domain (CTD) of the CUC has transactivation activity. Domain
      swapping experiments revealed that the functional specificity of the CUC for
      promoting adventitious shoot formation resides in the highly conserved NAC
      domain, not in the CTD in which motifs specific to the CUC subfamily are located.
      Taken together, these observations suggest that CUC proteins transactivate the
      target genes involved in SAM formation and organ separation through a specific
      interaction between the NAC domain and the promoter region of the target genes.

PMID- 15500464
TI  - Genetic engineering of glycinebetaine synthesis in tomato protects seeds, plants,
      and flowers from chilling damage.
AB  - Tomato (Lycopersicon esculentum Mill.) plants, which normally do not accumulate
      glycinebetaine (GB), are susceptible to chilling stress. Exposure to temperatures
      below 10 degrees C causes various injuries and greatly decreases fruit set in
      most cultivars. We have transformed tomato (cv. Moneymaker) with a chloroplast
      targeted codA gene of Arthrobacter globiformis, which encodes choline oxidase to
      catalyze the conversion of choline to GB. These transgenic plants express codA
      and synthesize choline oxidase, while accumulating GB in their leaves and
      reproductive organs up to 0.3 and 1.2 micromol g(-1) fresh weight (FW),
      respectively. Their chloroplasts contain up to 86% of total leaf GB. Over various
      developmental phases, from seed germination to fruit production, these GB
      accumulating plants are more tolerant of chilling stress than their wild-type
      counterparts. During reproduction, they yield, on average, 10-30% more fruit
      following chilling stress. Endogenous GB contents as low as 0.1 micromol g(-1) FW
      are apparently sufficient to confer high levels of tolerance in tomato plants, as
      achieved via transformation with the codA gene. Exogenous application of either
      GB or H2O2 improves both chilling and oxidative tolerance concomitant with
      enhanced catalase activity. These moderately increased levels of H2O2 in codA
      transgenic plants, as a byproduct of choline oxidase-catalyzed GB synthesis,
      might activate the H2O2-inducible protective mechanism, resulting in improved
      chilling and oxidative tolerances in GB-accumulating codA transgenic plants.
      Thus, introducing the biosynthetic pathway of GB into tomato through metabolic
      engineering is an effective strategy for improving chilling tolerance.

PMID- 15500465
TI  - AtPTR1, a plasma membrane peptide transporter expressed during seed germination
      and in vascular tissue of Arabidopsis.
AB  - For the efficient translocation of organic nitrogen, small peptides of two to
      three amino acids are posited as an important alternative to amino acids. A new
      transporter mediating the uptake of di- and tripeptides was isolated from
      Arabidopsis thaliana by heterologous complementation of a peptide transport
      deficient Saccharomyces cerevisiae mutant. AtPTR1 mediated growth of S.
      cerevisiae cells on different di- and tripeptides and caused sensitivity to the
      phytotoxin phaseolotoxin. The spectrum of substrates recognized by AtPTR1 was
      determined in Xenopus laevis oocytes injected with AtPTR1 cRNA under voltage
      clamp conditions. AtPTR1 not only recognized a broad spectrum of di- and
      tripeptides, but also substrates lacking a peptide bond. However, amino acids,
      omega-amino fatty acids or peptides with more than three amino acid residues did
      not interact with AtPTR1. At pH 5.5 AtPTR1 had an apparent lower affinity (K(0.5)
      = 416 microm) for Ala-Asp compared with Ala-Ala (K(0.5) = 54 microm) and Ala-Lys
      (K(0.5) = 112 microm). Transient expression of AtPTR1/GFP fusion proteins in
      tobacco protoplasts showed that AtPTR1 is localized at the plasma membrane. In
      addition, transgenic plants expressing the beta-glucuronidase (uidA) gene under
      control of the AtPTR1 promoter demonstrated expression in the vascular tissue
      throughout the plant, indicative of a role in long-distance transport of di- and
      tripeptides.

PMID- 15500467
TI  - Stress hormone-independent activation and nuclear translocation of mitogen
      activated protein kinases in Arabidopsis thaliana during ozone exposure.
AB  - Changing environmental conditions, atmospheric pollutants and resistance
      reactions to pathogens cause production of reactive oxygen species (ROS) in
      plants. ROS in turn trigger the activation of signaling cascades such as the
      mitogen-activated protein kinase (MAPK) cascade and accumulation of plant
      hormones, jasmonic acid, salicylic acid (SA), and ethylene (ET). We have used
      ozone (O3) to generate ROS in the apoplast of wild-type Col-0 and hormonal
      signaling mutants of Arabidopsis thaliana and show that this treatment caused a
      transient activation of 43 and 45 kDa MAPKs. These were identified as AtMPK3 and
      AtMPK6. We also demonstrate that initial AtMPK3 and AtMPK6 activation in response
      to O3 was not dependent on ET signaling, but that ET is likely to have secondary
      effects on AtMPK3 and AtMPK6 function, whereas functional SA signaling was needed
      for full-level AtMPK3 activation by O3. In addition, we show that AtMPK3, but not
      AtMPK6, responded to O3 transcriptionally and translationally during O3 exposure.
      Finally, we show in planta that activated AtMPK3 and AtMPK6 are translocated to
      the nucleus during the early stages of O3 treatment. The use of O3 to induce
      apoplastic ROS formation offers a non-invasive in planta system amenable to
      reverse genetics that can be used for the study of stress-responsive MAPK
      signaling in plants.

PMID- 15500468
TI  - Potassium carrier TRH1 is required for auxin transport in Arabidopsis roots.
AB  - Disruption of the TRH1 potassium transporter impairs root hair development in
      Arabidopsis, and also affects root gravitropic behaviour. Rescue of these
      morphological defects by exogenous auxin indicates a link between TRH1 activity
      and auxin transport. In agreement with this hypothesis, the rate of auxin
      translocation from shoots to roots and efflux of [3H]IAA in isolated root
      segments were reduced in the trh1 mutant, but efflux of radiolabelled auxin was
      accelerated in yeast cells transformed with the TRH1 gene. In roots,
      Pro(TRH1):GUS expression was localized to the root cap cells which are known to
      be the sites of gravity perception and are central for the redistribution of
      auxin fluxes. Consistent with these findings, auxin-dependent DR5:GUS promoter
      reporter construct was misexpressed in the trh1 mutant indicating that partial
      block of auxin transport through the root cap is associated with upstream
      accumulation of the phytohormone in protoxylem cells. When [K+] in the medium was
      reduced from 20 to 0.1 mm, wild type roots showed mild agravitropic phenotype and
      DR5:GUS misexpression in stelar cells. This pattern of response to low external
      [K+] was also affected by trh1 mutation. We conclude that the TRH1 carrier is an
      important part of auxin transport system in Arabidopsis roots.

PMID- 15500469
TI  - A single amino acid substitution in the Arabidopsis FIERY1/HOS2 protein confers
      cold signaling specificity and lithium tolerance.
AB  - Low temperature induces the expression of many plant genes through undefined
      signaling pathways. To gain insight into cold signal transduction mechanisms, we
      isolated Arabidopsis mutants that exhibited altered regulation of low temperature
      induced gene expression. One such mutant, hos2, was shown previously to have an
      enhanced induction of stress-responsive genes by cold, whereas the expression of
      these genes under osmotic stress or the phytohormone absciscic acid (ABA)
      treatments was not affected. Here we further define the targets of HOS2 by
      examining the regulation of upstream cold-specific CBF transcription factor
      genes. It was found that the transcript levels of CBF2 and CBF3 were
      significantly higher in hos2 mutant plants than in the wild type under cold
      treatments, suggesting that HOS2 may act upstream of CBFs. The HOS2 gene was
      cloned using a map-based strategy. Surprisingly, HOS2 is identical to the FIERY1
      gene that we had described previously. FIERY1 is a general negative regulator
      that controls cold, osmotic stress, and ABA signal transduction and possesses
      inositol polyphosphate 1-phosphatase activity. The hos2 mutation rendered the
      HOS2/FIERY1 recombinant protein completely inactive in the cold but did not
      substantially affect its activity at warm temperatures. Interestingly, the hos2
      mutant protein is extremely tolerant to Li+. This study provides a unique example
      of a single amino acid substitution in a critical regulator that can lead to
      conditional changes in protein functions and distinct plant phenotypes. The
      results reinforce the notion that phosphoinositols are important second
      messengers in cold signal transduction, and shed light on how the diversity of
      plant tolerance to cold and other abiotic stresses may evolve due to variations
      in a common molecular switch.

PMID- 15500470
TI  - The MADS-box gene DAL1 is a potential mediator of the juvenile-to-adult
      transition in Norway spruce (Picea abies).
AB  - Progression through the plant life cycle involves change in many essential
      features, most notably in the capacity to reproduce. The transition from a
      juvenile vegetative and non-reproductive to an adult reproductive phase is
      gradual and can take many years; in the conifer Norway spruce, Picea abies,
      typically 20-25 years. We present a detailed analysis of the activities of three
      regulatory genes with potential roles in this transition in Norway spruce: DAL1,
      a MADS-box gene related to the AGL6 group of genes from angiosperms, and the two
      LEAFY-related genes PaLFY and PaNLY. DAL1 activity is initiated in the shoots of
      juvenile trees at an age of 3-5 years, and then increases with age, whereas both
      LFY genes are active throughout the juvenile phase. The activity of DAL1 further
      shows a spatial pattern along the stem of the tree that parallels a similar
      gradient in physiological and morphological features associated with maturation
      to the adult phase. Constitutive expression of DAL1 in transgenic Arabidopsis
      plants caused a dramatic attenuation of both juvenile and adult growth phases;
      flowers forming immediately after the embryonic phase of development in severely
      affected plants. Taken together, our results support the notion that DAL1 may
      have a regulatory role in the juvenile-to-adult transition in Norway spruce.

PMID- 15500471
TI  - The BOS loci of Arabidopsis are required for resistance to Botrytis cinerea
      infection.
AB  - Three Botrytis-susceptible mutants bos2, bos3, and bos4 which define independent
      and novel genetic loci required for Arabidopsis resistance to Botrytis cinerea
      were isolated. The bos2 mutant is susceptible to B. cinerea but retains wild-type
      levels of resistance to other pathogens tested, indicative of a defect in a
      response pathway more specific to B. cinerea. The bos3 and bos4 mutants also show
      increased susceptibility to Alternaria brassicicola, another necrotrophic
      pathogen, suggesting a broader role for these loci in resistance. bos4 shows the
      broadest range of effects on resistance, being more susceptible to avirulent
      strain of Pseudomonas syringae pv. tomato. Interestingly, bos3 is more resistant
      than wild-type plants to virulent strains of the biotrophic pathogen Peronospora
      parasitica and the bacterial pathogen P. syringae pv. tomato. The Pathogenesis
      Related gene 1 (PR-1), a molecular marker of the salicylic acid (SA)-dependent
      resistance pathway, shows a wild-type pattern of expression in bos2, while in
      bos3 this gene was expressed at elevated levels, both constitutively and in
      response to pathogen challenge. In bos4 plants, PR-1 expression was reduced
      compared with wild type in response to B. cinerea and SA. In bos3, the mutant
      most susceptible to B. cinerea and with the highest expression of PR-1, removal
      of SA resulted in reduced PR-1 expression but no change to the B. cinerea
      response. Expression of the plant defensin gene PDF1-2 was generally lower in bos
      mutants compared with wild-type plants, with a particularly strong reduction in
      bos3. Production of the phytoalexin camalexin is another well-characterized plant
      defense response. The bos2 and bos4 mutants accumulate reduced levels of
      camalexin whereas bos3 accumulates significantly higher levels of camalexin than
      wild-type plants in response to B. cinerea. The BOS2, BOS3, and BOS4 loci may
      affect camalexin levels and responsiveness to ethylene and jasmonate. The three
      new mutants appear to mediate disease responses through mechanisms independent of
      the previously described BOS1 gene. Based on the differences in the phenotypes of
      the bos mutants, it appears that they affect different points in defense response
      pathways.

PMID- 15500472
TI  - WRINKLED1 encodes an AP2/EREB domain protein involved in the control of storage
      compound biosynthesis in Arabidopsis.
AB  - The accumulation of storage compounds during seed development ensures the
      survival of the young seedling, and also provides nutrition to humans and animals
      in the form of foods and feeds. The putative AP2/EREBP transcription factor
      WRINKLED1 (WRI1) is involved in the regulation of seed storage metabolism in
      Arabidopsis. A splicing mutant allele, wri1-1, caused the reduction of seed oil
      accumulation. Glycolysis was compromised in this mutant, rendering developing
      embryos unable to efficiently convert sucrose into precursors of triacylglycerol
      biosynthesis. Expression of the WRINKLED1 cDNA under the control of the
      cauliflower mosaic virus 35S-promoter led to increased seed oil content.
      Moreover, the ectopic expression of the WRINKLED1 cDNA caused the accumulation of
      triacylglycerols in developing seedlings. This effect depended upon the presence
      of glucose in the growth medium or other sugars readily metabolized to glucose.
      Oil-accumulating seedlings showed aberrant development consistent with a
      prolonged embryonic state.

PMID- 15500473
TI  - A subset of hypersensitive response marker genes, including HSR203J, is the
      downstream target of a spermine signal transduction pathway in tobacco.
AB  - A cellular signal transduction pathway induced by the polyamine, spermine (Spm),
      and transmitted by mitochondrial dysfunction is proposed in tobacco. In this
      investigation, we further resolve the pathway by identifying a subset of
      hypersensitive response (HR) marker genes as downstream components. In a previous
      report, we identified harpin-induced 1 (HIN1) and two closely related genes as
      responsive to Spm. Other HR marker genes, HSR203J, HMGR, HSR201, and HSR515, are
      also Spm-responsive. Induction of these HR marker genes, including HIN1, by Spm
      was suppressed by pre-treatment with antioxidants, calcium channel blockers,
      inhibitor of mitochondrial permeability transition pore openings, and blockers of
      amine oxidase/polyamine oxidase. Such quenching is also observed for Spm-induced
      activation of two mitogen-activated protein kinases (MAPKs), salicylic acid
      induced protein kinase (SIPK), and wound-induced protein kinase (WIPK), and
      upregulation of the WIPK gene, suggesting that all these components are part of
      the same signaling pathway. Furthermore, gain-of-function and loss-of-function
      studies on MAPK cascade members reveal that the expression of Spm-induced HR
      marker genes varies with respect to involvement of SIPK/WIPK activation.

PMID- 15500474
TI  - The mitochondrion--an organelle commonly involved in programmed cell death in
      Arabidopsis thaliana.
AB  - Plant cells undergoing programmed cell death (PCD) at late stages typically show
      chromatin condensation and endonucleolytic cleavage prior to obvious membrane or
      organelle ultrastructural changes. To investigate possible early PCD-associated
      events, we used microscopic observations and flow cytometry to quantitate
      mitochondrial membrane potential (DeltaPsim) changes during PCD at the single
      cell and population levels using Arabidopsis protoplasts. A DeltaPsim loss was
      commonly induced early during plant PCD and was important for PCD execution, as
      evidenced by the concomitant reduction of the change in DeltaPsim and PCD by
      cyclosporin A, which inhibits mitochondrial permeability transition pores in
      animal cells. DeltaPsim loss occurred prior to nuclear morphological changes and
      was only associated with mitochondrial cytochrome c release (an apoptotic trigger
      in animals) in response to one of three PCD elicitors. Three different stimuli in
      wild type implicated DeltaPsim changes in PCD: ceramide, protoporphyrin IX, and
      the hypersensitive response elicitor AvrRpt2. Additionally, the behavior of the
      conditional ectopic cell death mutant accelerated cell death2 and ACD2
      overproducing plants also implicated DeltaPsim alteration as key for PCD
      execution. Because ACD2 is largely a chloroplast component in mature plants, the
      observation that the cell death in acd2 mutants requires changes in mitochondrial
      functions implicates communication between chloroplasts and mitochondria in
      mediating PCD activation. We suggest that DeltaPsim loss is a common early marker
      in plant PCD, similar to what has been documented in animals. However, unlike in
      animal cells, in plant cells, mitochondrial cytochrome c release is not an
      obligatory step in PCD control.

PMID- 15500466
TI  - Sequence composition, organization, and evolution of the core Triticeae genome.
AB  - We investigated the composition and the basis of genome expansion in the core
      Triticeae genome using Aegilops tauschii, the D-genome donor of bread wheat. We
      sequenced an unfiltered genomic shotgun (trs) and a methylation-filtration (tmf)
      library of A. tauschii, and analyzed wheat expressed sequence tags (ESTs) to
      estimate the expression of genes and transposable elements (TEs). The sampled D
      genome sequences consisted of 91.6% repetitive elements, 2.5% known genes, and
      5.9% low-copy sequences of unknown function. TEs constituted 68.2% of the D
      genome compared with 50% in maize and 14% in rice. The DNA transposons
      constituted 13% of the D-genome compared with 2% in maize. TEs were methylated
      unevenly within and among elements and families, and most were transcribed which
      contributed to genome expansion in the core Triticeae genome. The copy number of
      a majority of repeat families increased gradually following polyploidization.
      Certain TE families occupied discrete chromosome territories. Nested insertions
      and illegitimate recombination occurred extensively between the TE families, and
      a majority of the TEs contained internal deletions. The GC content varied
      significantly among the three sequence sets examined ranging from 42% in tmf to
      46% in trs and 52% in the EST. Based on enrichment of genic sequences,
      methylation-filtration offers one option, although not as efficient as in maize,
      for isolating gene-rich regions from the large genome of wheat.

PMID- 15500476
TI  - Virus-induced gene silencing as a tool for functional genomics in a legume
      species.
AB  - Virus-induced gene silencing (VIGS) is an attractive reverse-genetics tool for
      studies of gene function. However, efficient VIGS has only been accomplished in a
      few plant species. In order to extend the application of VIGS, we examined
      whether a VIGS vector based on Pea early browning virus (PEBV) would produce
      recognizable phenotypes in Pisum sativum. A plasmid vector of PEBV was modified
      to allow agro-inoculation and insertion of heterologous sequences. cDNA fragments
      of the P. sativum phytoene desaturase (PDS), LEAFY (LFY) and KORRIGAN1 (KOR1)
      homologues were inserted into the PEBV RNA2 vector, replacing the genes required
      for nematode transmission. Pisum sativum inoculated with PEBV carrying a fragment
      of PsPDS developed characteristic photo-bleached leaves and this phenotype was
      associated with a significant reduction in PsPDS mRNA. The P. sativum homologue
      of LFY is known as UNIFOLIATA (UNI). Plants inoculated with PEBV carrying a
      fragment of UNI developed distorted flowers and leaves with modified
      architecture, which are also observed in UNI-mutants. In Arabidopsis thaliana,
      the KOR1-mutant is characterized by an extreme dwarf phenotype. Pisum sativum
      plants inoculated with PEBV carrying a fragment of PsKOR1 displayed a significant
      reduction in height and inhibition of root growth. The PEBV VIGS vector did not
      affect the ability of P. sativum to flower, set seeds, and form nodules
      characteristic of symbiosis with rhizobium. These results suggest that the PEBV
      vector can be applied to functional genomics in a legume species to study genes
      involved in a wide range of biological processes.

PMID- 15500475
TI  - Tandem inverted repeat system for selection of effective transgenic RNAi strains
      in Chlamydomonas.
AB  - RNA interference (RNAi), the double-stranded RNA (dsRNA) triggered post
      transcriptional gene silencing, is becoming a powerful tool for reverse genetics
      studies. Stable RNAi, induced by the expression of inverted repeat (IR)
      transgenes, has been achieved in protozoa, algae, fungi, plants, and metazoans.
      However, the level of gene silencing is often quite variable, depending on the
      type of construct, transgene copy number, site of integration, and target gene.
      This is a hindrance in functional genomics studies, where it is desirable to
      suppress target genes reliably to analyze unknown phenotypes. Consequently, we
      explored strategies for direct selection of effective transgenic RNAi lines in
      Chlamydomonas reinhardtii. We initially attempted to suppress expression of the
      Rubisco small subunit multigene family by placing an IR, homologous to the
      conserved coding sequence, in the 3'UTR of a transgene conferring resistance to
      bleomycin. However, this approach was fairly inefficient at inducing RNAi as many
      strains displayed defective transgene integration, resulting in partial or
      complete deletion of the IR, or low levels of dsRNA expression, presumably due to
      transcriptional silencing of the integrated IR transgenes. To overcome these
      problems we designed a system consisting of tandem IR transgenes that
      consistently triggered co-silencing of a gene with a selectable RNAi-induced
      phenotype (encoding tryptophan synthase beta subunit) and another gene of
      interest (encoding either Ku80, an RNA-binding protein, or a thioredoxin
      isoform). We anticipate that this approach will be useful for generating stable
      hypomorphic epi-mutants in high-throughput phenotypic screens.

PMID- 15500478
TI  - Clinical and genetic aspects of X-linked ectodermal dysplasia in the dog -- a
      review including three new spontaneous cases.
AB  - This review presents the clinical, dermato-histopathological and genetic features
      of canine X-linked ectodermal dysplasia in previously reported cases and in three
      new spontaneous cases. The condition is compared with anhidrotic ectodermal
      dysplasia in humans and, based on current genetic concepts, we suggest that the
      two conditions are caused by the same gene and, consequently, represent a single
      pathological entity that affects both humans and dogs.

PMID- 15500479
TI  - Adrenal steroid hormone concentrations in dogs with hair cycle arrest (Alopecia
      X) before and during treatment with melatonin and mitotane.
AB  - The purpose of the study was to evaluate intermediate adrenal steroid hormones
      (ISH) in neutered dogs with hair cycle arrest (Alopecia X) during treatment with
      melatonin, and to see if hair re-growth is associated with sex hormone
      concentrations within the normal ranges. Twenty-nine neutered, euthyroid, and
      normo-cortisolemic dogs were enrolled in the study (23 Pomeranians, three
      keeshonds, two miniature poodles, and one Siberian husky). Coat assessment and an
      ACTH stimulation test were performed pre-treatment and approximately every 4
      months for a year post treatment. Melatonin was administered initially at 3-6 mg,
      every 12 h. Based on clinical progression, each dog was continued on the current
      dose of melatonin, given an increased dose of melatonin or changed to mitotane.
      Partial to complete hair re-growth occurred in 14/23 Pomeranians, and partial re
      growth in 3/3 keeshond and 1/2 poodle dogs. A Siberian husky dog failed to re
      grow hair. Fifteen dogs had partial hair re-growth at the first re-evaluation.
      Melatonin dosage was increased in eight dogs but only one had improved hair re
      growth. On mitotane treatment, partial to complete hair re-growth was seen in 4/6
      dogs and no re-growth in 2/6 dogs. No significant decrease in sex hormone
      concentrations were seen during melatonin or mitotane treatment. Concentrations
      of ISH in dogs with hair re-growth did not differ significantly from pre
      treatment values. At the completion of the study, androstenedione, progesterone
      and 17-hydroxyprogesterone were still above reference ranges in 21, 64 and 36%,
      respectively, of dogs with partial to complete hair re-growth. In conclusion, 62%
      of dogs had partial to complete hair re-growth. However, not all dogs with hair
      re-growth had concentrations of ISH within the normal range.

PMID- 15500480
TI  - Treatment of canine Alopecia X with trilostane.
AB  - Sixteen Pomeranians and eight miniature poodles presenting with clinical signs of
      alopecia X, elevated blood concentrations of 17-hydroxyprogesterone post
      stimulation with adrenocorticotropic hormone and increased urinary
      cortisol/creatinine ratios were treated with trilostane, a competitive inhibitor
      of 3beta-hydroxysteroid dehydrogenase. Trilostane was given once or twice daily
      at a mean dose of 10.85 mg kg(-1) day(-1). Adrenal function was evaluated with a
      follow-up of 28 months in the Pomeranians and 33 months in the miniature poodles.
      Treatment with trilostane led to complete hair re-growth in 85% of the
      Pomeranians and in all of the miniature poodles within 4 to 8 weeks. No adverse
      events attributed to treatment with trilostane were recognized. The hair re
      growth might have been the result of a down-regulation of adrenal steroids and/or
      of the noncompetitive inhibition of the oestrogen receptors at the hair follicle
      level.

PMID- 15500481
TI  - Investigation on the clinical efficacy and safety of 0.1% tacrolimus ointment
      (Protopic) in canine atopic dermatitis: a randomized, double-blinded, placebo
      controlled, cross-over study.
AB  - Topical tacrolimus is successfully used in people with atopic dermatitis.
      Preliminary studies in dogs with atopic dermatitis using tacrolimus in a
      compounded lotion formulation indicated that tacrolimus significantly decreased
      erythema and pruritus according to investigator, but no significant improvement
      was reported by the dog owners. The objectives of this study were to evaluate the
      clinical efficacy and safety of the commercially available 0.1% tacrolimus
      ointment (Protopic) in dogs with atopic dermatitis. The study was designed as a
      double-blinded, placebo-controlled, cross-over study. Selected dogs were
      allocated to either tacrolimus or placebo for 4 weeks. After 4 weeks there was a
      wash-out period of 2 weeks and treatments were switched. Twelve dogs completed
      the study. Clinical signs were scored. Blood samples were collected for complete
      blood count, chemistry panels and tacrolimus levels at week 0 and 4 of each
      treatment. Tacrolimus ointment significantly decreased severity of symptoms for
      both owners and investigators at the end of the trial. When the same dogs
      received the placebo, there were no differences between week 0 and week 4 scores.
      Dogs with localized disease responded better than dogs with generalized disease.
      Tacrolimus was detected in the blood of animals receiving the active ingredient.
      Levels were below the level of toxicity and no adverse effects were reported in
      any of the dogs. No changes in complete blood count and chemistry parameters were
      detected between groups or within groups. In conclusion, tacrolimus appears to be
      a safe alternative treatment in dogs with atopic dermatitis, especially in those
      with localized disease.

PMID- 15500482
TI  - Determination of threshold concentrations of allergens and evaluation of two
      different histamine concentrations in canine intradermal testing.
AB  - The purpose of this study was to determine the optimal histamine concentration
      and allergen threshold concentrations for canine intradermal testing. Thirty
      healthy dogs were tested using two different concentrations of histamine and four
      different concentrations of each allergen. The optimal histamine concentration
      was determined to be 1:10 000 w/v. The threshold concentration was at least 1750
      PNU/mL for all tested grasses, weeds, trees, moulds and insects, except for fleas
      which was as least 1:500 w/v. For Dermatophagoides pteronyssinus, the optimal
      threshold concentration was 250 PNU/mL, whereas for Dermatophagoides farinae and
      Tyrophagus putrescentiae, it was 100 PNU/mL. Threshold concentration for all
      epidermals except human dander was at least 1250 PNU/mL. The optimal threshold
      concentration for human dander was 300 PNU/mL. Our results suggest that the
      currently used 1:100 000 w/v concentration of histamine and the 1000 PNU/mL
      concentration for most grasses, weeds, trees, moulds, epidermals and insects may
      not be appropriate for canine intradermal testing.

PMID- 15500483
TI  - Alterations of mast cell mediator production and release by gamma-linolenic and
      docosahexaenoic acid.
AB  - The purpose of our investigations was to evaluate the supposed beneficial effects
      of gamma-linolenic (GLA) and docosahexaenoic acid (DHA) in a canine mastocytoma
      cell line (C2) as a model for canine atopic dermatitis. Cells were cultured in a
      basic medium (DEH) and in DEH supplemented with 14.3 microM GLA (DEH-GLA) or 14.3
      microM DHA (DEH-DHA) for 8 days. Chymase and tryptase activity, as well as
      histamine and prostaglandin (PG)E(2) release were measured. To stimulate
      histamine and PGE(2) release, cells were incubated with the wasp venom peptide
      mastoparan (50 microM) for 30 min. GLA increased tryptase activity and decreased
      histamine release after C2 stimulation. DHA diminished PGE(2) production in
      activated C2. These results support the prescription of GLA- and DHA-enriched
      diets to reduce inflammatory signs in canine atopic dermatitis.

PMID- 15500484
TI  - A herd level analysis of a Corynebacterium pseudotuberculosis outbreak in a dairy
      cattle herd.
AB  - Corynebacterium pseudotuberculosis infection in an Israeli dairy cattle herd is
      described. The disease was characterized by ulcerative granulomatous lesions,
      which occurred in an epidemic form. Thirty-two cows and two heifers were
      affected, the ratio of the number affected to number at risk being 17.5 : 1 and
      9.5 : 1, respectively. The culling rate was 50% of the affected animals. Most of
      the affected animals were cows (91.2%), with one first-calving cow (2.9%) and two
      heifers (5.9%) also affected. The infection occurred during the summer to autumn
      months (August-December), and lasted 118 days. The incubation period is about 2
      months. The disease appeared in two clinical forms - cutaneous and mastitic - or
      as a mixed form. C. pseudotuberculosis organisms that were isolated from the
      ulcerative granulomatous lesions and from milk samples failed to reduce nitrate.
      A decrease in milk production (4%) and an increase in the bulk-milk somatic cell
      count from a herd mean of 240 x 10(3) mL(-1) to 460 x 10(3) mL(-1) were noted
      during the morbidity period. The organism was isolated from milk samples of eight
      animals (25%). Clinical, epizootiological and microbiological aspects of the
      infection are described.

PMID- 15500485
TI  - Diagnosis of flea allergy dermatitis: comparison of intradermal testing with flea
      allergens and a FcepsilonRI alpha-based IgE assay in response to flea control.
AB  - The objective of this study was to evaluate the accuracy of in vivo and in vitro
      tests in the diagnosis of flea allergy dermatitis in comparison with history,
      clinical signs and response to flea control. Intradermal testing using four
      different sources of flea allergens and FcepsilonRIalpha-based immunoglobulin
      (Ig)E assays were performed in 15 flea-allergic dogs, 15 atopic dogs and 15 dogs
      infested with fleas but showing no clinical signs of skin disease. Sensitivity,
      specificity, negative predictive value, positive predictive value and accuracy
      were calculated for all five tests and results varied greatly. Sensitivity,
      specificity and overall accuracy were 27, 83 and 64%, respectively, for one
      extract (Isotec), 67, 90 and 82% for another extract (Greer), 93, 90 and 91% for
      flea saliva, 40, 90 and 73% for the recombinant Cte f 1 both produced by Heska
      Corp. and 87, 53 and 64% for a FcepsilonRIalpha-based IgE assay. These results
      indicate that intradermal testing with flea extracts is more accurate in the
      diagnosis of flea allergy dermatitis than in vitro tests. Moreover, pure flea
      saliva used as a reagent for intradermal testing provided the best results in
      terms of sensitivity, specificity and overall accuracy although the Greer
      extract, a whole body flea extract, also allowed a good correlation between
      intradermal testing results and clinical approach to flea allergy dermatitis
      diagnosis.

PMID- 15500486
TI  - Mycobacterium goodii infection in a dog with concurrent hyperadrenocorticism.
AB  - Abstract A 9-year-old Boston terrier was diagnosed with multifocal, nodular
      panniculitis caused by an organism belonging to the Mycobacterium smegmatis group
      by histological evaluation and bacteriological identification. The mycobacterial
      species was identified by direct gene sequence analysis and confirmed to be
      Mycobacterium goodii. Treatment using doxycycline and ciprofloxacin was
      successfully implemented for the mycobacterial panniculitis over a period of 9
      months. Concurrent pituitary-dependent hyperadrenocorticism (Cushing's disease)
      was also identified using routine diagnostic methods and mitotane therapy was
      implemented. There was follow-up for 14 months after cessation of antimicrobial
      therapy with no recurrence of mycobacterial infection. Although cutaneous
      infections are frequently recognized as complications of canine pituitary
      dependent hyperadrenocorticism, concurrent mycobacterial panniculitis due to any
      rapidly growing mycobacterium has not previously been reported. This is the first
      confirmed case of mycobacterial panniculitis due to M. goodii infection in a dog
      and also the first of any rapidly growing mycobacterial infection in a dog with
      concurrent endogenous Cushing's disease.

PMID- 15500488
TI  - An unending supply of 'unusual' complications from central venous catheters.

PMID- 15500489
TI  - General anesthesia, surgery and hospitalization in children and their effects
      upon cognitive, academic, emotional and sociobehavioral development - a review.
AB  - We reviewed current knowledge about cumulative and differential consequences of
      general anesthesia, surgery and hospitalization upon cognitive, academic,
      emotional and sociobehavioral development in children. Our strategy was to search
      the databases Pub Med and PsycINFO for all articles published between 1990 and
      May 2002. Based on the abstracts, we included all articles that related in any
      way to our subject of interest. Analysis of the articles showed preoperative
      anxiety as the main contributing factor to perioperative negative developmental
      effects. These were generally limited in duration and reversible. Research in
      this area tries to investigate predictors of increased anxiety, as well as the
      efficacy of different interventional programs for reduction of preoperative
      anxiety. We found no studies attempting to differentiate the relative influences
      of 'anesthetic stress', 'surgical stress' and 'hospitalization stress' on
      'negative outcomes', 'areas of development affected' or 'duration of effects'.
      There are very few studies on academic and cognitive consequences. There is a
      need for more research in this area to provide useful guidelines for clinicians,
      to identify risk situations and to prevent negative outcomes.

PMID- 15500490
TI  - Herbal medicine use by children presenting for ambulatory anesthesia and surgery.
AB  - BACKGROUND: Herbal medicine use has become increasingly popular throughout the
      world. Some of these agents may have serious interactions with anesthetic drugs.
      Children may potentially be more vulnerable to such interactions because of
      altered drug handling. While the prevalence of herbal medicine use by children
      with some chronic illnesses has been estimated, the incidence of this in a
      population of otherwise healthy children admitted for minor ambulatory anesthesia
      and surgery is currently unknown. METHODS: Parents of 601 children presenting
      consecutively for ambulatory surgery were asked to complete a questionnaire
      detailing administration of herbal medicines to their child. RESULTS: This study
      identified that 6.4% of children were currently taking an herbal preparation;
      while a further 10.1% had taken an herbal medicine in the past. Echinacea and
      arnica were the commonest used herbal remedies. A significant number of children
      had taken agents which may interact with anesthesia and surgery: St John's Wort,
      valerian, garlic and gingko. Information on herbal medicines was mostly obtained
      by parents from nonmedical sources. CONCLUSIONS: A total of 16.6% of children had
      a current or past history of ingestion of herbal medicines. This finding may have
      implications for the perioperative management of children presenting for day-case
      surgery.

PMID- 15500491
TI  - Careful physical examination is essential in the preoperative assessment of
      children for dental extractions under general anesthesia.
AB  - BACKGROUND: Physical examination is routinely carried out for the preoperative
      assessment of children, but is it of value in day stay community dental surgery?
      METHODS: A prospective survey of new diagnoses made on children presenting for
      community dental extractions and compared with children having nondental surgery.
      RESULTS: Five of 216 children for dental extractions were seen with new diagnoses
      made, with a variety of conditions including patent ductus arteriosus, aortic
      stenosis, ventricular septal defect and obstructive sleep apnea. No new diagnoses
      were made in 294 nondental children in the same period. CONCLUSIONS: Physical
      examination provides a useful adjunct to the history in children undergoing
      community dental extraction. There is potentially significant morbidity
      undiagnosed in apparently fit children presenting for dental surgery.

PMID- 15500492
TI  - Paradoxical reaction following intravenous midazolam premedication in pediatric
      patients - a randomized placebo controlled trial of ketamine for rapid
      tranquilization.
AB  - BACKGROUND: Paradoxical reactions to benzodiazepines include restlessness,
      violent behavior, physical assault, act of self-injury and need for restraints.
      These may occur at variable times after administration. This study was designed
      to determine the incidence of paradoxical reactions following intravenous
      midazolam premedication in pediatric patients and to compare the efficacy of
      extra doses of midazolam with low-dose intravenous ketamine to rapidly
      tranquillize them. METHODS: A total of 706 ASA I, II children scheduled for
      elective surgery were given intravenous midazolam premedication. Children who
      developed a paradoxical reaction were randomly divided into three equal groups to
      receive: (i) extra midazolam, (ii) ketamine, or (iii) placebo as the test drug
      for treatment of paradoxical reaction. Ease of rapid tranquillization and need
      for a rescue tranquillizer (i.e. ketamine; irrespective of patient group) were
      compared among the three groups. RESULTS: Twenty-four (3.4%) children developed
      paradoxical reaction after midazolam premedication. Those who received ketamine
      as the test drug responded rapidly to ketamine. But the responses of the other
      two groups to their test drug were poor and the majority of them required
      ketamine as rescue tranquillizer (six in midazolam, seven in placebo, but no
      patient in the ketamine group; P < 0.05). CONCLUSIONS: The results of this study
      demonstrate that ketamine is an effective drug for the treatment of paradoxical
      reaction following intravenous midazolam premedication. The exact mechanisms of
      these reactions and how it is aborted by ketamine are not clear.

PMID- 15500493
TI  - Vertical infraclavicular brachial plexus block in children: a preliminary study.
AB  - BACKGROUND: Brachial plexus blockade is a well-established technique in upper
      limb surgery. Among the infraclavicular approaches, the vertical infraclavicular
      brachial plexus (VIP) block is easy to perform and has a large spectrum of nerve
      blockade. The aim of this preliminary study was to determine the ease,
      effectiveness, safety, and duration of the VIP block in pediatric trauma surgery.
      METHODS: Fifty-five patients (ASA physical status I and II, age range 5-17 years
      old) scheduled for upper limb trauma surgery received a VIP block under light
      general anesthesia, using 0.5 ml x kg(-1) of ropivacaine 0.5%. The number of
      attempts and time to perform the block, the occurrence of a surgical response,
      the visual analogue score (VAS) scores, the incidence of complications and the
      duration of the block were evaluated. RESULTS: The brachial plexus was found
      easily at the first or second attempt in 85% (47 of 55) of the cases, in 15%
      (eight of 55) of the cases it was localized after three to four attempts. The
      mean time to perform the block was 3.35 +/- 3.37 min. Ninety-eight percentage (54
      of 55) of the blockades were effective for surgery and in just one case was
      ineffective. The VAS scores at the end of the procedure in 100% (55 of 55) of the
      cases were <3. There were no cases with clinical signs of pneumothorax nor
      inadvertent puncture of major vessels. Two patients developed a Horner's syndrome
      and in one a mild superficial hematoma at the puncture site occurred. The mean
      sensory block duration was 8.45 +/- 1.71 h and the mean motor block duration was
      6.52 +/- 2.50 h. CONCLUSIONS: In this preliminary study, the VIP block was easy
      to perform, effective and free of major complications for pediatric trauma
      surgery. With the doses of ropivacaine we used it was useful for intra- and
      postoperative analgesia.

PMID- 15500494
TI  - Continuous ventilation technique for laryngeal mask airway (LMA) removal after
      fiberoptic intubation in children.
AB  - BACKGROUND: Fiberoptic tracheal intubation through the laryngeal mask airway
      (LMA) is a simple technique to establish a safe airway in neonates and infants
      with a difficult airway. The technique, however, is complicated by the removal of
      the laryngeal mask from the patient's mouth because of the similarity in length
      of the LMA and the tracheal tube. METHODS: Several solutions have been presented
      to stabilize the tracheal tube within the trachea during withdrawal of the LMA.
      With all these techniques ventilation of the patient is interrupted. RESULTS: We
      present a modified technique, using a double tube assembly, which allows
      uninterrupted ventilation of the patient during withdrawal of the LMA from the
      patient's mouth. CONCLUSIONS: The technique is simple and safe, can be performed
      without hurry and carries potential advantages for neonates and children with
      limited cardiorespiratory reserve.

PMID- 15500495
TI  - Use of a remifentanil-propofol mixture for pediatric flexible fiberoptic
      bronchoscopy sedation.
AB  - BACKGROUND: Flexible fiberoptic bronchoscopy is an important diagnostic tool for
      pediatric pulmonologists. Because of its favorable respiratory profile, ketamine
      has become a popular sedative for this procedure, but may be associated with
      unpleasant emergence reactions in the older child. Remifentanil is a newer, ultra
      short acting opioid that has been shown to provide effective sedation and cough
      suppression for fiberoptic bronchoscopy when combined with intermittent propofol
      boluses. However, delivery of these agents as a combined, single infusion has not
      been described. METHODS: Children > or =2 years of age undergoing fiberoptic
      bronchoscopy were enrolled. Remifentanil was mixed in a single syringe with
      undiluted propofol giving final drug concentrations of 10 mg x ml(-1) of propofol
      and 15-20 microg x ml(-1) of remifentanil. Sedation was induced with a bolus of
      approximately 0.1 ml x kg(-1) of this mixture and maintained by titrating the
      drip throughout the procedure. Vital signs, sedative effectiveness, recovery
      patterns, and complications were prospectively recorded. RESULTS: Fifteen
      patients aged 9.0 +/- 5.3 years were sedated. Sedation was induced with 1.2 +/-
      0.4 mg x kg(-1) propofol (2.4 +/- 0.8 microg x kg(-1) remifentanil) and
      maintained with 4.1 +/- 1.8 mg x kg(-1) x h(-1) propofol (0.13 +/- 0.06 microg x
      kg(-1) x min(-1) remifentanil). Five patients received low-dose ketamine to
      augment sedation. The maximal decrease in respiratory rate was 6.1 +/- 5.3 b x
      min(-1) (27.6 +/- 21%) and no patient became hypoxemic. All procedures were
      completed easily without significant complication. Patients recovered to baseline
      13.3 +/- 8.5 min following infusion discontinuation. CONCLUSIONS: A
      remifentanil/propofol mixture provided effective sedation and rapid recovery in
      pediatric patients undergoing fiberoptic bronchoscopy.

PMID- 15500496
TI  - Anesthesia for removal of inhaled foreign bodies in children.
AB  - BACKGROUND: Foreign body aspiration may be a life-threatening emergency in
      children requiring immediate bronchoscopy under general anesthesia. Both
      controlled and spontaneous ventilation techniques have been used during
      anesthesia for bronchoscopic foreign body removal. There is no prospective study
      in the literature comparing these two techniques. This prospective randomized
      clinical trial was undertaken to compare spontaneous and controlled ventilation
      during anesthesia for removal of inhaled foreign bodies in children. METHODS:
      Thirty-six children posted for rigid bronchoscopy for removal of airway foreign
      bodies over a period of 2 years and 2 months in our institution were studied.
      After induction with sleep dose of thiopentone or halothane, they were randomly
      allocated to one of the two groups. In group I, 17 children were ventilated after
      obtaining paralysis with suxamethonium. In group II, 19 children were breathing
      halothane spontaneously in 100% oxygen. RESULTS: All the patients in the
      spontaneous ventilation group had to be converted to assisted ventilation because
      of either desaturation or inadequate depth of anesthesia. There was a
      significantly higher incidence of coughing and bucking in the spontaneous
      ventilation group compared with the controlled ventilation group (P = 0.0012).
      CONCLUSION: Use of controlled ventilation with muscle relaxants and inhalation
      anesthesia provides an even and adequate depth of anesthesia for rigid
      bronchoscopy.

PMID- 15500497
TI  - Cardiac tamponade in a newborn because of umbilical venous catheterization: is
      correct position safe?
AB  - Cardiac tamponade is a rare but life-threatening complication of umbilical venous
      catheterization in the newborn. Most complications from central venous catheters
      are related to incorrect position of the catheter and it is emphasized to confirm
      the position of the catheter tip after placement in order to avoid possible
      complications. We present an unusual complication of cardiac tamponade because of
      umbilical venous catheterization in a term newborn which is extremely rare with
      correct location of the catheter tip at the junction of inferior vena cava and
      right atrium. We suggest that correct position never guarantees uneventful
      catheterization in the newborn. In any infant with a central venous catheter in
      situ who deteriorates clinically, pericardial effusion/cardiac tamponade must be
      considered and appropriate action taken.

PMID- 15500498
TI  - Bilateral consolidation of the lungs in a preterm infant: an unusual central
      venous catheter complication.
AB  - We describe a case of bilateral parenchymal consolidation with sudden respiratory
      distress in a preterm baby as a complication of peripherally inserted central
      catheter (PICC) dislocation. The X-rays showed bilateral pulmonary consolidation
      with the catheter tip initially located in the right, and later in the left
      pulmonary artery. The catheter was withdrawn. As soon as the catheter was
      repositioned all clinical signs and symptoms disappeared. Neonatologists should
      consider the possibility of dramatic respiratory distress deriving from PICC
      dislocation. Careful tip catheter placement and conscientious monitoring may
      reduce morbidity.

PMID- 15500499
TI  - Liver biopsy complicated by hemorrhage in a patient with ARC syndrome.
AB  - ARC syndrome is a rare disorder consisting of arthrogryposis, renal tubular
      acidosis and cholestatic liver disease. We report the case of a 5-week-old
      patient who underwent a percutaneous liver biopsy complicated by hemorrhage, and
      was subsequently diagnosed with ARC syndrome. A review of the literature
      demonstrates that these patients are at increased risk of bleeding caused by
      platelet dysfunction. The evaluation and management of unexpected hemorrhage in
      pediatric patients as a result of undiagnosed congenital bleeding problems is
      discussed.

PMID- 15500500
TI  - General anesthesia in an infant with X-linked myotubular myopathy.
AB  - We present a 20-week-old infant with the X-linked form of myotubular myopathy who
      required anesthesia for a Nissen fundoplication procedure where the response to
      nondepolarizing neuromuscular blockade was evaluated.

PMID- 15500501
TI  - Anesthesia for a child with Wolf-Hirshhorn syndrome.

PMID- 15500503
TI  - The intubation depth marker: the confusion of the black line.

PMID- 15500502
TI  - Inadvertent bronchogram during cardiac catheterization.

PMID- 15500504
TI  - One shot spinal morphine injection for postthoracotomy pain control in children.

PMID- 15500506
TI  - Serotonin in the gut: pretty when it gets down to the nitty gritty.

PMID- 15500507
TI  - Real-time detection of serotonin release from enterochromaffin cells of the
      guinea-pig ileum.
AB  - Serotonin (5-hydroxytryptamine; 5-HT) containing enterochromaffin (EC) cells may
      detect chemical or mechanical stimuli in the intestinal lumen and respond with
      release of 5-HT. The aim of this study was to use real-time electrochemical
      detection methods to detect release of 5-HT from small numbers of EC cells. In
      guinea-pig ileum, basal release of 5-HT from the unstimulated, unparalyzed
      intestine was composed of individual release events (8.4 +/- 1.8 events, 0.33 +/-
      0.06 Hz) of different amplitudes but with similar kinetics. Local compression of
      the mucosa with the electrode evoked peak 5-HT release of 12.3 +/- 2.8 micromol
      L(-1) with a sustained release of 3.0 +/- 0.7 micromol L(-1). Brief application
      of acetylcholine (ACh) or carbachol elicited a transient peak (5.7 +/- 1.3
      micromol L(-1) occurring at 35 +/- 18 s, n = 9) followed by cyclic release of 5
      HT (9.7 +/- 2.2 events, 0.40 +/- 0.13 Hz, n = 6). This study shows that the
      release of 5-HT occurs rapidly as individual events from a small number of cells
      and can reach very high concentrations locally.

PMID- 15500508
TI  - Human enteric neuropathies: morphology and molecular pathology.
AB  - The aim of this study is to review current understanding of the molecular and
      morphological pathology of the enteric neuropathies affecting motor function of
      the human gastrointestinal tract and to evaluate the described pathological
      entities in the literature to assess whether a new nosology may be proposed. The
      authors used PUBMED and MEDLINE searches to explore the literature pertinent to
      the molecular events and pathology of gastrointestinal motility disorders
      including achalasia, gastroparesis, intestinal pseudo-obstruction, colonic
      inertia and megacolon in order to characterize the disorders attributable to
      enteric gut neuropathies. This scholarly review has shown that the pathological
      features are not readily associated with clinical features, making it difficult
      for a patient to be classified into any specific category. Individual patients
      may manifest more than one of the morphological and molecular abnormalities that
      include: aganglionosis, neuronal intranuclear inclusions and apoptosis, neural
      degeneration, intestinal neuronal dysplasia, neuronal hyperplasia and
      ganglioneuromas, mitochondrial dysfunction (syndromic and non-syndromic),
      inflammatory neuropathies (caused by cellular or humoral immune mechanisms),
      neurotransmitter diseases and interstitial cell pathology. The pathology of
      enteric neuropathies requires further study before an effective nosology can be
      proposed. Carefully studied individual cases and small series provide the basic
      framework for standardizing the collection and histological evaluation of tissue
      obtained from such patients. Combined clinical and histopathological studies may
      facilitate the translation of basic science to the clinical management of
      patients with enteric neuropathies.

PMID- 15500509
TI  - High-resolution manometry predicts the success of oesophageal bolus transport and
      identifies clinically important abnormalities not detected by conventional
      manometry.
AB  - BACKGROUND AND AIMS: High-resolution manometry (HRM) is a recent development in
      oesophageal measurement; its value in the clinical setting remains a matter of
      controversy. (i) We compared the accuracy with which bolus transport could be
      predicted from conventional manometry and HRM. (ii) The clinical value of HRM was
      assessed in a series of patients with endoscopy-negative dysphagia in whom
      conventional investigations had been non-diagnostic. METHOD: (i) Control subjects
      and patients with endoscopy-negative dysphagia underwent concurrent HRM and video
      fluoroscopy. Ninety-five records were reviewed using HRM with spatiotemporal plot
      and conventional line plots of the pressure data derived from the same recording.
      (ii) The HRM and notes of patients with endoscopy-negative dysphagia and abnormal
      bolus transport were analysed to identify additional information provided by the
      new technique. RESULTS: (i) Receiver operating characteristic analysis
      demonstrated that HRM predicts the presence of abnormal bolus transport more
      accurately than conventional manometry. (ii) HRM identified clinically important
      motor dysfunction not detected by manometry and radiography. These included
      localized disturbances of peristalsis and abnormal movement of the lower
      oesophageal sphincter during oesophageal spasm. CONCLUSION: The HRM predicts
      bolus movement more accurately than conventional manometry and identifies
      clinically relevant oesophageal dysfunction not detected by other investigations
      including conventional manometry.

PMID- 15500510
TI  - A new measurement of oesophago-gastric junction competence.
AB  - Knowledge of the competence of the oesophago-gastric junction (OGJ) is
      fundamental to the understanding of gastro-oesophageal reflux disease (GORD), a
      disorder with a high incidence among the general population. A catheter with a
      bag 9.5 cms long mounted towards the distal end was swallowed by three
      volunteers. Using manometry readings and the point of respiratory inversion as a
      guide the probe was placed in the OGJ. The bag was distended with saline at a
      fixed rate volume before and after the administration of butylscopolamine to
      block cholinergic-mediated contractile smooth muscle activity. Using impedance
      planimetry three cross-sectional areas (CSA) measurements were made between three
      pairs of electrodes with 4 mm between each electrode on the catheter placed
      inside the ballon. Using the law of Laplace, CSA and pressure data could be
      calculated to give wall tension. Tension rose in all volunteers as the radius
      increased and it was higher towards the proximal end of the OGJ indicating that
      this measurement can be used to show the distensibility of the OGJ at different
      degrees of opening. This technique could be useful in identifying changes in the
      competence of the lower oesophageal sphincter in some patients with GORD.

PMID- 15500511
TI  - Oesophageal transport of solid dosage forms depends on body position, swallowing
      volume and pharyngeal propulsion velocity.
AB  - Knowledge about transit of solid dosage forms (SDF) in the gastrointestinal tract
      is incomplete. Detection of magnetically marked capsules (MMC) via
      superconducting quantum interference device (SQUID) allows monitoring of
      oesophageal transport of SDF with high tempospatial resolution. The aim of the
      study was to investigate the influence of body position, volume at swallowing,
      and oesophageal motility on orogastric transport of SDF. In 360 measurements we
      determined tempospatial characteristics of orogastric transit of SDFs by a SQUID
      device in six volunteers. They swallowed MMCs with various amounts of water in
      upright and supine position with and without simultaneous oesophageal manometry.
      Orogastric transit time, oesophageal transport velocity and rate of oesophageal
      retention of SDF depend on swallowing volume and body position at all
      experimental conditions. At 50 mL water bolus and in upright position, the
      retention rate depends on the pharyngeal propulsion velocity, and the transport
      velocity of MMCs in the oesophageal body are faster than the propulsive
      oesophageal contractions. Body position, swallowing volume and pharyngeal
      propulsion velocity markedly influence the oesophageal transport of SDF. They
      should be taken in upright body position with at least 50 mL of water to minimize
      entrapment in the oesophagus.

PMID- 15500512
TI  - Directed endoscopic mucosal mapping of normal and dysrhythmic gastric slow waves
      in healthy humans.
AB  - Frequency and amplitude characteristics of normal and dysrhythmic slow waves in
      different gastric regions are poorly characterized. Using endoscopic mucosal
      mapping, we quantified slow wave frequency and power at predetermined sites under
      control conditions and with glucagon. Twelve healthy volunteers underwent
      gastroscopy with midazolam. Bipolar recording electrodes were directed to 12, 7,
      and 2 cm proximal to the pylorus along the greater and lesser curvatures.
      Dominant frequencies at all sites were 2.96 +/- 0.07 cycles min(-1) (cpm). Powers
      of the dominant frequency were 59 +/- 7% lower 12 cm vs 2 cm from the pylorus (P
      < 0.01), but were similar along the greater and lesser curvatures. Glucagon (0.3
      mg IV) decreased dominant frequencies (1.40 +/- 0.10 cpm, P < 0.01) and elicited
      power reductions which varied by region (36 +/- 37% at 12 cm vs 79 +/- 20% at 2
      cm, P < 0.01). Comparing dominant frequencies from mucosal recordings and
      electrogastrography revealed minimal slow wave uncoupling. In conclusion,
      endoscopic mucosal mapping demonstrates slow wave power gradients from the
      proximal to distal stomach under normal conditions. Glucagon evokes bradygastria
      with minimal uncoupling and elicits inhibitory effects on slow wave power which
      are more potent in the distal antrum. This method provides insight into the
      mechanisms of action of gastric slow wave dysrhythmic stimuli.

PMID- 15500513
TI  - Comparison of gastric volumes in response to isocaloric liquid and mixed meals in
      humans.
AB  - AIMS: To compare gastric volume responses to ingestion of isocaloric liquid or
      mixed (solid-liquid) meals and document the intra- and interindividual
      reproducibility of gastric volume measurement using single photon emission
      computed tomography (SPECT) imaging after i.v. 99mTc-pertechnetate. METHODS:
      Eight healthy volunteers performed two studies at least 9 months apart. Gastric
      volumes were measured after a 317 kcal liquid nutrient meal. Within 2 weeks of
      the second liquid meal study, participants performed a third study, ingesting an
      isocaloric mixed meal. The order of the mixed and second liquid meals was
      randomized; Bland-Altman plot displayed data on repeated studies with liquid meal
      and paired t-test compared gastric volumes after mixed or liquid isocaloric
      meals. RESULTS: Fasting and postprandial gastric volumes associated with the two
      liquid meals were not significantly different; inter- and intra-individual
      coefficients of variation were 13 and 13.8%. In response to the mixed meal, there
      was a lower absolute postprandial volume and lower change in gastric volume over
      fasting volume compared with the response to the liquid meal (P = 0.0001).
      CONCLUSION: The SPECT measurement of gastric volumes in response to a nutrient
      liquid meal is reproducible. The magnitude of the volume response is greater
      after the liquid meal compared with the isocaloric mixed meal.

PMID- 15500514
TI  - Neuronal correlates of gastric pain induced by fundus distension: a 3T-fMRI
      study.
AB  - Visceral hypersensitivity in gastric fundus is a possible pathogenesis for
      functional dyspepsia. The cortical representation of gastric fundus is still
      unclear. Growing evidence shows that the insula, but not the primary or secondary
      somatosensory region (SI or SII), may be the cortical target for visceral pain.
      Animal studies have also demonstrated that amygdala plays an important role in
      processing visceral pain. We used fMRI to study central projection of stomach
      pain from fundus balloon distension. We also tested the hypothesis that there
      will be neither S1 nor S2 activation, but amygdala activation with the fundus
      distension. A 3T-fMRI was performed on 10 healthy subjects during baseline,
      fullness (12.7 +/- 0.6 mmHg) and moderate gastric pain (17.0 +/- 0.8 mmHg). fMRI
      signal was modelled by convolving the predetermined psychophysical response.
      Statistical comparisons were performed between conditions on a group level.
      Gastric pain activated a wide range of cortical and subcortical structures,
      including thalamus and insula, anterior and posterior cingulate cortices, basal
      ganglia, caudate nuclei, amygdala, brain stem, cerebellum and prefrontal cortex
      (P < 0.001). A subset of these neuronal substrates was engaged in the central
      processing of fullness sensation. SI and SII were not activated during the fundus
      stimulation. In conclusion, the constellation of neuronal structures activated by
      fundus distension overlaps the pain matrices induced musculocutaneous pain, with
      the exception of the absence of SI or SII activation. This may account for the
      vague nature of visceral sensation/pain. Our data also confirms that the insula
      and amygdala may act as the central role in visceral sensation/pain, as well as
      in the proposed sensory-limbic model of learning and memory of pain.

PMID- 15500515
TI  - Investigation of the utility of colorectal function tests and Rome II criteria in
      dyssynergic defecation (Anismus).
AB  - Although 30-50% of constipated patients exhibit dyssynergia, an optimal method of
      diagnosis is unclear. Recently, consensus criteria have been proposed but their
      utility is unknown. To examine the diagnostic yield of colorectal tests,
      reproducibility of manometry and utility of Rome II criteria. A total of 100
      patients with difficult defecation were prospectively evaluated with anorectal
      manometry, balloon expulsion, colonic transit and defecography. Fifty-three
      patients had repeat manometry. During attempted defecation, 30 showed normal and
      70 one of three abnormal manometric patterns. Forty-six patients fulfilled Rome
      criteria and showed paradoxical anal contraction (type I) or impaired anal
      relaxation (type III) with adequate propulsion. However, 24 (34%) showed impaired
      propulsion (type II). Forty-five (64%) had slow transit, 42 (60%) impaired
      balloon expulsion and 26 (37%) abnormal defecography. Defecography provided no
      additional discriminant utility. Evidence of dyssynergia was reproducible in 51
      of 53 patients. Symptoms alone could not differentiate dyssynergic subtypes or
      patients. Dyssynergic patients exhibited three patterns that were reproducible:
      paradoxical contraction, impaired propulsion and impaired relaxation. Although
      useful, Rome II criteria may be insufficient to identify or subclassify
      dyssynergic defecation. Symptoms together with abnormal manometry, abnormal
      balloon expulsion or colonic marker retention are necessary to optimally identify
      patients with difficult defecation.

PMID- 15500516
TI  - Mechanism of butyrate-induced hyperpolarization of cultured rat myenteric
      neurones.
AB  - Short-chain fatty acids produced by the bacterial fermentation of carbohydrates
      are present in high concentrations within the colonic lumen and have been shown
      to alter the excitability of enteric neurones. The present study was designed to
      investigate the mechanisms of butyrate-induced changes in membrane potential of
      myenteric neurones. Myenteric neurones from 4-10-day-old rats were isolated from
      the small and large intestine by an enzymatic digestion with collagenase and kept
      in culture. Membrane potential was measured with the whole-cell patch-clamp
      technique and the intracellular Ca2+ concentration was measured with the fura-2
      method. The short-chain fatty acid butyrate (10-100 mmol L(-1)) induced a
      reversible and concentration-dependent hyperpolarization of the membrane with a
      half-maximal effect at 30 mmol L(-1). The hyperpolarization evoked by butyrate
      (50 mmol L(-1)) was strongly inhibited by charybdotoxin (10(-7) mol L(-1)), a
      specific blocker of Ca2+ -dependent K+ channels. The butyrate-induced
      hyperpolarization was resistant against blockade of phospholipase C by U-73122
      (10(-5) mol L(-1)), and resistant against inclusion of heparin (6 x 10(-6) mol L(
      1)), an inositol-1,4,5-trisphosphate receptor antagonist, in the patch-pipette.
      In contrast, ruthenium red (3 x 10(-5) mol L(-1)), an inhibitor of ryanodine
      receptors, significantly reduced both the hyperpolarization of the membrane as
      well as the increase in the intracellular Ca2+ concentration evoked by butyrate.
      Even in neurones permeabilized with saponin (10 mg L(-1)), butyrate was able to
      stimulate a release of stored intracellular Ca2+ suggesting a direct action of
      the short-chain fatty acid at the stores without mediation of a soluble
      intracellular second messenger.

PMID- 15500517
TI  - Mediators of non-adrenergic non-cholinergic inhibitory neurotransmission in
      porcine jejunum.
AB  - The purpose of this study was to determine the non-adrenergic non-cholinergic
      inhibitory neurotransmitter in pig jejunum. Intracellular electrical activity was
      recorded from circular smooth muscle cells. Inhibitory junction potentials (IJPs)
      evoked by electrical field stimulation were inhibited by tetrodotoxin (1 micromol
      L(-1)), omega-conotoxin GVIA (0.1 micromol L(-1)) tetrodotoxin, apamin (1
      micromol L(-1)), 1-[6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl]
      1H-pyrrole-2,5-dione (U-73122; 10 micromol L(-1)) but not by N omega-nitro-l
      arginine (l-NNA; 100 micromol L(-1)), haemoglobin (10 micromol L(-1)), 1H
      [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 micromol L(-1)) or 9
      (tetrahydro-2-furyl)adenine (SQ-22536; 10 micromol L(-1)). S-nitroso-N
      acetylpenicillamine (SNAP) hyperpolarized the membrane potential. This was
      inhibited by ODQ (3 micromol L(-1)) and charybdotoxin (0.1 micromol L(-1)).
      Adenosine-5-triphosphate (ATP; 100 micromol L(-1)) and 2-methylthio ATP (2-MeS
      ATP; 100 micromol L(-1)) did not hyperpolarize the membrane potential and 6-N-N
      diethyl-beta- gamma -dibromomethylene-d-adenosine-5'-triphosphate (ARL67156; 100
      micromol L(-1)) did not modify IJPs. Carbon monoxide (CO; 10%) and tricarbonyl
      dichlororuthenium dimer ([Ru(CO3Cl2)]2; 100 micromol L(-1)) hyperpolarized the
      membrane potential however zinc, copper and tin protoporphyrin IX (100 micromol
      L(-1)) did not alter IJPs. Vasoactive intestinal peptide (VIP) hyperpolarized the
      membrane potential but 4-Cl-d-Phe6-Leu17-VIP (1 micromol L(-1)) did not modify
      IJPs. Pituitary adenylate cyclase activating peptide (PACAP)38 (0.5 micromol L(
      1)) hyperpolarized the membrane potential. This was inhibited by apamin (1
      micromol L(-1)) but not by tetrodotoxin (1 micromol L(-1)). Pituitary adenylate
      cyclase activating peptide6-38 (1 micromol L(-1)) inhibited IJPs. These data
      suggest that inhibitory neurotransmission in pig jejunum is mediated partly by
      PACAP.

PMID- 15500518
TI  - Quantitative changes in gastric mucosal glycoproteins: effect of cholinergic
      agonist and vagal nerve stimulation in the rat.
AB  - The role of the vagus nerve and cholinergic mechanisms in the control of the rat
      gastric mucin and protein (PROT) release in vivo was investigated. Under urethane
      anaesthesia (1.25 g kg(-1)), the rats had their gastric lumen perfused with
      saline. Mucus secretion was measured as a function of adherent mucus on the
      mucosa surface and the luminal content of sialic acids (SIA), galactose (GAL),
      pyruvate and PROT. Electrical stimulation of the vagi significantly increased the
      levels of mucus (3.23 +/- 025 microg g(-1) tissue, P < 0.05), free sialic acid
      (FS) (0.18 +/- 0.04 mg mL(-1), P < 0.05) and PROT (0.25 +/- 0.003 mg mL(-1), P <
      0.05) when compared with control animals. Bilateral cervical vagotomy had no
      significant effect on adherent mucus or basal levels of PROT, SIA and GAL (P >
      0.05) with respect to the control. In both vagotomized and vagal intact animals,
      the cholinergic agonist (carbachol, 200 mg kg(-1)) significantly increased PROT,
      adherent mucus and FS (P < 0.05) and decreased bound sialic acid (P > 0.05).
      There were no visible haemorrhagic streaks on the gastric mucosa of vagotomized,
      vagal intact and carbachol-treated animals. The results suggest that vagus nerve
      does not exert a tonic control on gastric glycoprotein secretion in vivo and that
      cholinergic effect on the mucus secreting cells may be implemented via the
      intrinsic nerves of the enteric nervous system.

PMID- 15500519
TI  - Pacemaker activity from submucosal interstitial cells of Cajal drives high
      frequency and low-amplitude circular muscle contractions in the mouse proximal
      colon.
AB  - The present study was aimed at elucidating how pacemaker activity (plateau
      potentials) (mean frequency: 15.9 +/- 2.8 times min(-1)) from submucosal
      interstitial cells of Cajal (ICC-SM) control spontaneous contractions in the
      mouse proximal colon. Mechanical activities in the circular muscle direction
      showed high-frequency (mean frequency: 15.6 +/- 2.7 times min(-1)) and low
      amplitude (mean amplitude: 0.01 +/- 0.005 g) (HFLA) rhythmic contractions.
      Simultaneous recordings of circular muscle mechanical activity and electrical
      activity from ICC-SM revealed that HFLA contractions were synchronized with
      plateau potentials (mean frequency: 15.9 +/- 2.8 times min(-1)). Although low
      frequency (3.5 +/- 2.1 times min(-1)) and high-amplitude (0.12 +/- 0.03 g) (LFHA)
      contractions in both longitudinal and circular muscle directions were
      synchronized with burst of action potentials in both muscle cells, these LFHA
      contractions were not synchronous with plateau potentials. Intracellular Ca2+
      release from the internal stores through IP3 receptors is not a major factor to
      generate both action potentials differently from plateau potentials. Neither
      tetrodotoxin nor atropine affected the plateau potentials. The results reveal
      that the pacemaker activity from ICC-SM drives only the spontaneous HFLA (one
      tenth amplitude of the LFHA circular and longitudinal muscle contractions)
      circular muscle contractions without control by enteric nerves.

PMID- 15500526
TI  - Hope, health work and quality of life in families of stroke survivors.
AB  - AIM: This paper reports a study to examine the relationships among hope, family
      health promotion, and quality of life after stroke, by testing hypotheses derived
      from the Developmental Model of Health and Nursing. BACKGROUND: Little attention
      has been given to the influences of family strengths on health promotion
      behaviours and quality of life after stroke. The majority of studies have focused
      on stroke survivors, not their spouses. METHOD: A descriptive, correlational
      study was carried out with 40 families of stroke survivors with moderate to
      severe functional impairments and their spouses. Both partners completed the
      Herth Hope Index (measure of hope), the Health Options Scale (measure of health
      work), the Reintegration to Normal Living Index (measure of quality of life) and
      a demographic questionnaire. RESULTS: For both partners, moderate, positive
      relationships were found between hope and health work (r = 0.52, r = 0.39, P <
      0.01) and between hope and quality of life (r = 0.59, r = 0.32, P < 0.05). Family
      health work was positively associated with quality of life of stroke survivors (r
      = 0.50, P </= 0.001), but not their spouses. Spouses' employment status, number
      of supports and functional independence at discharge predicted 40.6% and 46.3% of
      the variance in quality of life for stroke survivors and spouses, respectively,
      with the combination of hope and health work contributing an additional 17.8% in
      predicting stroke survivors' quality of life but no additional variance to the
      prediction of spouses' quality of life. CONCLUSION: Theoretical relationships of
      the Developmental Model of Health and Nursing were supported for stroke
      survivors, but the model was less useful in explaining spouses' experiences of
      hope, health work and quality of life. Findings provide direction for identifying
      'at risk' families and raise awareness of the contribution of caregiver burden to
      quality of life in families of stroke survivors.

PMID- 15500527
TI  - Patient approaches to clinical conversations in the palliative care setting.
AB  - AIM: The aim of this paper is to report a study exploring patients' understanding
      of their discussions about end-of-life care with nurses in a palliative care
      setting. BACKGROUND: It is assumed that nurses are central players in patients'
      major decisions about their care, yet minimal information is available about the
      complexity of patient-nurse interaction in palliative care, and patients' views
      of the impact of such interactions on decisions that are made. METHOD: A modified
      version of grounded theory was used to collect and analyse interview data
      collected in 2001-2002 with a convenience sample of 11 patients in a palliative
      care setting. Interviews focused on each patient's selection of two decisions
      they had made in the past 6 months that had involved nurses in the decision
      making process. FINDINGS: Processes were identified between nurses and patients
      that facilitated or blocked open discussion and discernment of patients'
      preferences for care. Six approaches that patients used in their conversations
      with nurses about their care: wait and see, quiet acceptance, active acceptance,
      tolerating bossiness, negotiation and being adamant. These approaches are
      described in terms of how they assisted or impeded autonomous decision-making.
      CONCLUSION: Palliative care patients often adopt passive roles and tend not to
      engage in important decision-making, for various reasons. Professionals need to
      be made aware of this, and should facilitate an open, trusting relationship with
      patients in order to ensure that important information passes freely in both
      directions. Professionals should learn to prioritize patient participation and
      negotiation in their work. With further research, it should be possible to
      identify the factors that will allow patients to take a more pro-active role in
      making decisions about their care, where desired.

PMID- 15500528
TI  - Testing the functional status model in patients with chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Patients with chronic obstructive pulmonary disease usually
      experience gradual functional status degradation, especially dyspnoea, which may
      affect their daily activities and, eventually, quality of life. A full
      understanding of both their physiological and psychological functional status is
      therefore beneficial for effective treatment and helping patients regain or
      maintain control of their lives. METHOD: Based on a non-experimental research
      design, 138 patients to test a hypothesized model of functional status in
      patients with chronic obstructive pulmonary disease, using structural equation
      modelling, were recruited from a medical center. Data were collected using
      questionnaires, 6-minute walking distance measurement, and pulmonary function
      test results recorded in patients' medical records. The proposed functional
      status model incorporated the exogenous variables disease severity and dyspnoea,
      and the endogenous variables age, exercise tolerance, fatigue, depression,
      anxiety, health perception and functional performance. Structural equation
      modelling with the lisrel software was used to establish a functional status
      model with those exogenous and endogenous variables. RESULTS: The results
      indicated a good fit between the proposed functional status model and the data
      collected [chi(2) = 8.84, P = 0.64, chi(2)/d.f. = 0.80, Goodness of Fit Index
      (GFI) = 0.98, adjusted GFI (AGFI) = 0.95, root mean square residual (RMR) = 0.04,
      Critical N (CN) = 384.26]. Coefficients for paths in the functional status model
      all demonstrated statistical significance. CONCLUSION: The functional status
      model was shown to consist of functional performance, functional capacity and
      other concepts, including disease severity, dyspnoea, age, exercise tolerance,
      fatigue, depression, anxiety and health perception. These results can be used to
      develop a suitable functional status model for chronic obstructive pulmonary
      disease, and could act as a reference for formulating future strategies and
      intervention procedures for further development of functional status.

PMID- 15500529
TI  - Adolescent mothers: resilience, family health work and health-promoting
      practices.
AB  - AIMS: This paper reports a study examining the relationships among mother's
      resilience, family health promotion (i.e. health work) and mother's health
      promoting lifestyle practices in single-parent families led by adolescent mothers
      by testing hypotheses derived from the Developmental Model of Health and Nursing.
      BACKGROUND: Research on families led by adolescent mothers has focussed primarily
      on negative maternal and child outcomes while ignoring the capacities of these
      families, including their efforts to promote the health and well-being of both
      mothers and children. METHODS: This replication study was conducted with
      convenience sample of 41 adolescent mothers recruited using a variety of
      strategies. Mothers were asked to provide verbal responses to items on three
      study instruments: The Resilience Scale, a measure of mother's resilience, the
      Health Options Scale, a measure of family health work and the Health Promoting
      Lifestyle Profile a measure of mother's health promoting lifestyle practices, as
      well as a demographic questionnaire. RESULTS: Consistent with the theory,
      moderate positive relationships were observed between mothers' resilience and
      both family health work (r = 0.34, P = 0.01) and mothers' health-promoting
      lifestyle practices (r = 0.42, P < 0.001). As predicted, moderate correlations
      were also observed between health work and mother's health promoting lifestyle
      practices (r = 0.62, P < 0.001). With the effects of employment status and
      professional support held constant, mother's resilience and health work explained
      30.2% of the variance in mother's health-promoting lifestyle practices.
      CONCLUSIONS: The study validates theoretical relationships among concepts in the
      developmental model of health and nursing and contributes to better understanding
      health promotion in families led by adolescent mothers.

PMID- 15500530
TI  - Experiences of infant-feeding decision-making among urban economically
      disadvantaged pregnant adolescents.
AB  - AIM: The aim of this paper is to report a pilot study of influencing factors in
      disadvantaged urban pregnant adolescents' decision-making about infant-feeding
      choices. BACKGROUND: Research related to decision-making among adolescents
      indicates that attitudinal, social, perceived control, and commitment factors are
      influential in choosing and initiating breast- or bottle-feeding. However, there
      is a need for further description of decision-making processes in disadvantaged
      teenagers before intervention research is done. METHODS: Focus group interviews
      with the Theory of Planned Behavior guiding the questioning were used with 14
      pregnant adolescents between 18 and 39 weeks of gestation and between the ages of
      14 and 18 in two obstetric clinics in Midwestern USA urban teaching hospitals.
      The majority of adolescents were African-American and primiparae. FINDINGS: The
      experiences of infant-feeding decision-making among pregnant adolescents were
      captured by two major themes: benefits vs. barriers of breastfeeding and bottle
      feeding, and independent choice vs. social influences. A common thread in these
      themes was ambivalence and uncertainty. The adolescents had both positive and
      negative attitudes toward methods, with many expressing their desire to combine
      breast- and bottle-feeding. Many reported the health benefits of breastfeeding,
      yet identified barriers of pain, public exposure, and the complexity of
      breastfeeding. They viewed bottle-feeding as automatic and simple, allowing
      freedom to leave the infant with others. Although adolescents were adamant that
      choice of feeding method was their independent decision, social and family
      influences were evident. CONCLUSIONS: Consistent with the Theory of Planned
      Behaviour and other research, attitudes, perceived social influences, and
      perceived control factors were influential to adolescents when choosing infant
      feeding methods. The findings suggest that adolescents need education on decision
      making, and are being used to fine-tune the interventions of a randomized
      clinical trial to investigate promoting and supporting breastfeeding among
      adolescent mothers.

PMID- 15500531
TI  - Sexual behaviour of nursing home residents: staff perceptions and responses.
AB  - AIMS: This paper presents the results of a study that investigated nursing home
      staff perceptions of affectionate and sexual behaviour of residents. BACKGROUND:
      Despite growing recognition of the importance of sexual expression among
      residents and a increasing willingness to discuss the topic, sexual activity for
      nursing home residents remains an ignored component of life satisfaction. Even
      when 'sexuality' has been included as part of a resident's plan of care, this may
      not mean that attention has been paid to maintaining that aspect of their life.
      Thus, nursing homes can mark the end of many types of freedom for older people.
      Given that intimate basic care is performed by others and often by members of the
      opposite sex, loss of sexual freedom may also occur. METHOD: A grounded theory
      approach was used to study staff working in nursing homes in Australia and
      Sweden. Data were generated through interviews and nominal groups with nursing
      home staff. Thirty women volunteered to be interviewed, and 18 others were
      involved in the three nominal group discussions; a further five participants were
      involved as key informants. FINDINGS: Staff perceptions and responses to
      residents' sexual behaviour were found to be influenced by their own level of
      comfort related to sexuality issues, and the ethos within the organization where
      they worked. The conceptual paradigm was termed 'Guarding Discomfort' and
      specified the ways in which staff guard against sexuality discomfort as well as
      the ways their behaviour fits within different types of organizations.
      CONCLUSION: Both staff and nursing home managers need to work toward developing a
      home environment that is supportive of residents' sexuality rights, that permits
      sexuality expression and promotes a culture where all people concerned are
      comfortable with sexuality issues.

PMID- 15500532
TI  - Effects of acupressure at the Sanyinjiao point on primary dysmenorrhoea.
AB  - AIM: This paper presents the findings of a study that assessed the effects of
      acupressure at the Sanyinjiao point on symptoms of primary dysmenorrhoea among
      adolescent girls. BACKGROUND: Dysmenorrhoea is the most common gynaecological
      disorder among adolescents. Traditional Chinese acupressure derived from
      acupuncture is a non-invasive technique. Despite renewed interest in the use of
      acupressure, relatively few studies have been undertaken to examine its effects
      on primary dysmenorrhoea. METHODS: An experimental study was conducted between
      December 2000 and August 2001. Participants were female students attending a
      technical college in Taiwan. None of the 69 participants had a prior history of
      gynaecological disease or secondary dysmenorrhoea, and all were rated higher than
      five for pain on a visual analogue scale from 0 to 10. The experimental group (n
      = 35) received acupressure at Sanyinjiao (above the ankle) while the control
      group (n = 34) rested for 20 min, while the control group underwent rest in the
      school health centre for 20 min without receiving acupressure. Fifty participants
      (30 experimental, 20 control) completed the 4-6-week follow-up session. Five
      instruments were used to collect pretest and post-test data at each session: (1)
      Visual Analogue Scale for pain; (2) the Short-Form McGill Pain Questionnaire; (3)
      the Menstrual Distress Questionnaire; (4) the Visual Analogue Scale for anxiety;
      and, for the experimental group only, (5) the Acupressure Self-Assessment Form.
      Data were analysed using the chi-square test, two-sample t-test and repeated
      measures two-way anova. RESULTS: Acupressure at Sanyinjiao during the initial
      session reduced the pain and anxiety typical of dysmenorrhoea. In the self
      treatment follow-up session, acupressure at Sanyinjiao significantly reduced
      menstrual pain but not anxiety. Thirty-one (87%) of the 35 experimental
      participants reported that acupressure was helpful, and 33 (94%) were satisfied
      with acupressure in terms of its providing pain relief and psychological support
      during dysmenorrhoea. CONCLUSION: The findings suggest that acupressure at
      Sanyinjiao can be an effective, cost-free intervention for reducing pain and
      anxiety during dysmenorrhoea, and we recommend its use for self-care of primary
      dysmenorrhoea.

PMID- 15500533
TI  - Methodological rigour within a qualitative framework.
AB  - AIM: This paper discusses the literature on establishing rigour in research
      studies. It describes the methodological trinity of reliability, validity and
      generalization and explores some of the issues relating to establishing rigour in
      naturalistic inquiry. BACKGROUND: Those working within the naturalistic paradigm
      have questioned the issue of using validity, reliability and generalizability to
      demonstrate robustness of qualitative research. Triangulation has been used to
      demonstrate confirmability and completeness and has been one means of ensuring
      acceptability across paradigms. Emerging criteria such as goodness and
      trustworthiness can be used to evaluate the robustness of naturalistic inquiry.
      DISCUSSION: It is argued that the transference of terms across paradigms is
      inappropriate; however, if we reject the concepts of validity and reliability, we
      reject the concept of rigour. Rejection of rigour undermines acceptance of
      qualitative research as a systematic process that can contribute to the
      advancement of knowledge. Emerging criteria for demonstrating robustness in
      qualitative inquiry, such as authenticity, trustworthiness and goodness, need to
      be considered. Goodness, when not seen as a separate construct but as an integral
      and embedded component of the research process, should be useful in assuring
      quality of the entire study. Triangulation is a tried and tested means of
      offering completeness, particularly in mixed-method research. When multiple types
      of triangulation are used appropriately as the 'triangulation state of mind',
      they approach the concept of crystallization, which allows for infinite variety
      of angles of approach. CONCLUSION: Qualitative researchers need to be explicit
      about how and why they choose specific legitimizing criteria in ensuring the
      robustness of their inquiries. A shift from a position of fundamentalism to a
      more pluralistic approach as a means of legitimizing naturalistic inquiry is
      advocated.

PMID- 15500534
TI  - The uses of photography in clinical nursing practice and research: a literature
      review.
AB  - AIMS: The aim of this paper is to report a study to identify themes and provide a
      'snap-shot' of the scope and uses of photography in clinical nursing practice and
      research. BACKGROUND: Despite the dominance of vision as a way of understanding
      the world in Western societies, the applications of photography in clinical
      nursing practice and research have not been well synthesized or reported in the
      literature. METHODS: A computerized search of CINAHL database was performed using
      the terms photographs, photography, photographic, photovoice, videorecording and
      videotaping. Hand searching for additional citations was also undertaken.
      FINDINGS: The identified papers on photography were categorized into broad themes
      that reflected the different applications to which photography had been applied:
      documentation and surveillance; therapeutic intervention; teaching, learning and
      evaluating performance; research methods; and descriptive and instructional
      literature. Approaches to the use of photography, as recorded in the nursing
      literature, are broad and include: wound surveillance, covert patient
      surveillance, photo essay, art therapy, self-portraits, life albums, simulated
      recall, participant observation, photovoice, photo hermeneutics, production of
      research scenarios, and video modelling. CONCLUSIONS: The most common
      applications of photography in nursing and related journals include photo
      elicitation to promote understanding in research, videorecording as a method of
      teaching and learning, and as a method of observation, with more creative
      approaches tending to be employed in health professions other than nursing. Few
      reports gave explanations of how researchers negotiated ethical concerns when
      seeking approval for studies in clinical settings, and few gave details of the
      processes of data analysis.

PMID- 15500535
TI  - The construction and development of health professions: where will it end?
AB  - AIM: The aim of this paper is to evaluate the construction and development of
      professional health work as it has occurred over the past 15 years in the UK and
      present an informed, speculative analysis of present and future health care work.
      BACKGROUND: Since the early 1990s, there has been a strong political imperative
      in the United Kingdom (UK) to develop existing roles in nursing and the allied
      health professions, blurring professional boundaries and emphasizing
      patient/client-centred care delivery. This has already led to major changes in
      professional work patterns and the privileging of interprofessional work. Many of
      these changes have been shaped and determined by cultural and economic
      considerations. DISCUSSION: The socio-political context for the major changes in
      the roles of non-medical professionals in the UK is explored to demonstrate both
      consistency and contradictions with postmodern, consumerist values. The
      theoretical concepts that underpin professional formation and enable
      professionalization are examined in relation to present health service drivers
      for interprofessional work and the development of advanced practice roles, noting
      similarities and differences in aspirations. CONCLUSION: While
      professionalization and role development appear to have benefited both
      professions and service users in the short-term, their adoption and
      institutionalization by policymakers are influencing its direction in ways which
      both may ultimately find troublesome.

PMID- 15500536
TI  - Sense of coherence among unemployed nurses.
AB  - AIMS: This paper reports a study assessing Finnish unemployed nurses' sense of
      coherence and the factors relating to it. BACKGROUND: During the 1990s, due to
      the widespread economic downturn in Finland, the nursing profession suffered from
      a high level of unemployment. Previous research has clearly indicated that
      unemployment is detrimental to health. It creates stress by disturbing a person's
      sense of identity and self-esteem and by disrupting social networks. In Finland,
      many studies have been conducted on the impact of unemployment, but have not
      examined the sense of coherence of unemployed nurses. METHODS: Data were
      collected in one Employment and Economic Development Centre area in Finland in
      1998. Structured questionnaires were used to collect data among Finnish
      unemployed nurses (n = 183), and included the General Health Questionnaire,
      measuring nurses' mental health; socio-demographic questions; and the 13-item
      version of the Sense of Coherence scale based on Antonovsky's salutogenic model
      to measure sense of coherence. RESULTS: Although the majority of unemployed
      nurses had a strong sense of coherence, many felt that during their period of
      unemployed they did not feel at ease, did not know what to do and had a sense of
      being unfairly treated. Daily household chores, on the whole, were perceived as
      meaningful. Income and the state of mental health were positively correlated with
      nurses' sense of coherence: the better the family income and state of mental
      health, the stronger was their sense of coherence. Because of the low response
      rate (less than 50%), the results might be skewed by those whose higher sense of
      coherence made them more motivated to complete the questionnaires. CONCLUSIONS:
      Many of the nurses reported low sense of coherence and poor general health.
      Special interventions should be designed to improve their sense of coherence and
      high motivation level, and to maintain their professional competence when they
      return to work. This kind of support may prevent further out-migration and
      nursing shortages from Finland and other industrialized countries.

PMID- 15500540
TI  - Timing of thyroid hormone action in the developing brain: clinical observations
      and experimental findings.
AB  - Abstract The original concept of the critical period of thyroid hormone (TH)
      action on brain development was proposed to identify the postnatal period during
      which TH supplement must be provided to a child with congenital hypothyroidism to
      prevent mental retardation. As neuropsychological tools have become more
      sensitive, it has become apparent that even mild TH insufficiency in humans can
      produce measurable deficits in very specific neuropsychological functions, and
      that the specific consequences of TH deficiency depends on the precise
      developmental timing of the deficiency. Models of maternal hypothyroidism,
      hypothyroxinaemia and congenital hyperthyroidism have provided these insights. If
      the TH deficiency occurs early in pregnancy, the offspring display problems in
      visual attention, visual processing (i.e. acuity and strabismus) and gross motor
      skills. If it occurs later in pregnancy, children are at additional risk of
      subnormal visual (i.e. contrast sensitivity) and visuospatial skills, as well as
      slower response speeds and fine motor deficits. Finally, if TH insufficiency
      occurs after birth, language and memory skills are most predominantly affected.
      Although the experimental literature lags behind clinical studies in providing a
      mechanistic explanation for each of these observations, recent studies confirm
      that the specific action of TH on brain development depends upon developmental
      timing, and studies informing us about molecular mechanisms of TH action are
      generating hypotheses concerning possible mechanisms to account for these
      pleiotropic actions.

PMID- 15500541
TI  - Interaction between norepinephrine, oxytocin, and nitric oxide in the stimulation
      of gonadotropin-releasing hormone release from proestrous rat basal hypothalamus
      explants.
AB  - In the proestrous female rat, norepinephrine, oxytocin and nitric oxide (NO) all
      participate in the regulation of the preovulatory gonadotropin-releasing hormone
      (GnRH) surge. Recent studies from our laboratory have demonstrated that oxytocin
      induces dose-dependent release of GnRH from proestrous basal hypothalamus
      explants. The present studies were undertaken to determine whether norepinephrine
      could also stimulate GnRH release from similar explants, to identify the
      receptors responsible for this effect and to investigate interactions between
      norepinephrine, oxytocin and NO. Norepinephrine significantly stimulated GnRH
      release from proestrous basal hypothalamus explants, and coadministration of the
      alpha(1)-adrenergic antagonist prazosin blocked this effect. Combined
      administration of oxytocin and norepinephrine stimulated significantly more GnRH
      release than either drug alone, and this stimulation was blocked by inhibition of
      NO synthase, or by an oxytocin receptor antagonist. NO production was measured
      from the same samples using a modified Griess reaction. Oxytocin, but not
      norepinephrine, significantly increased NO production, as did norepinephrine and
      oxytocin in combination. Oxytocin receptor antagonist administration attenuated
      the stimulation of NO production by norepinephrine/oxytocin. These results
      demonstrate for the first time that oxytocin and norepinephrine dramatically
      stimulate GnRH release from basal hypothalamus explants harvested on the
      afternoon of proestrus, and indicate that this involves oxytocin receptor and NO
      dependent mechanisms.

PMID- 15500542
TI  - Ghrelin-induced growth hormone release from isolated rat anterior pituitary cells
      depends on intracellullar and extracellular Ca2+ sources.
AB  - Ghrelin, a novel growth hormone (GH)-releasing peptide, was isolated from the rat
      stomach as an endogenous ligand to the growth hormone secretagogues receptor. It
      is known that ghrelin stimulates the release of GH from the rat anterior
      pituitary gland, but the intracellular signal cascade in somatotrophs has not yet
      been clarified. In this study, using an isolated cell perifusion system, we
      examined whether ghrelin- and growth hormone-releasing hormone (GHRH)-induced GH
      secretion from rat pituitary cells depends on intra- and extracellular Ca(2+) and
      voltage-gated Ca(2+) channels. For this purpose, we first measured ghrelin- or
      GHRH-stimulated GH concentration following treatment with reduced extracellular
      Ca(2+) and/or thapsigargin, an endoplasmic reticulum Ca(2+) ATPase inhibitor.
      Reductions in the extracellular Ca(2+) concentration to 0.25 mM and to 0 mM
      resulted in decreases in ghrelin-stimulated GH secretion to 81% and 39% and
      decreases in GHRH-induced GH secretion to 83% and 13%, respectively, compared to
      the levels in the case of 2.5 mM Ca(2+) concentration, suggesting that
      extracellular Ca(2+) is essential for both ghrelin- and GHRH-induced GH
      secretion. Pretreatment with thapsigargin resulted in a reduction in ghrelin
      induced GH secretion to approximately 60% of the control level, but GHRH
      treatment had not effect on the GH secretion. Moreover, preincubation with
      thapsigargin and 0 mM extracellular Ca(2+) concentration resulted in significant
      inhibition of GHRH- and ghrelin-induced GH secretion. Subsequently, to determine
      whether ghrelin-stimulated GH secretion was induced through voltage-gated Ca(2+)
      channels, we measured the ghrelin-stimulated GH concentration following treatment
      with nifedipine, an L-type Ca(2+) channel inhibitor, and found that the amount of
      GH secretion was reduced to 44% of the control level. Furthermore, by replacement
      of extracellular Na(2+) in the medium with N-methyl-D(-)-glucamine, an
      impermeable molecule, GH secretion was reduced to 47%. In this study, we
      demonstrated that the GH-stimulatory effect of ghrelin, unlike that of GHRH, is
      achieved through both intracellular and extracellular Ca(2+) sources and that
      ghrelin-induced extracellular Ca(2+) influx involves an L-type voltage-gated
      Ca(2+) channel and Na(+) influx.

PMID- 15500543
TI  - Voltage- and Ca2+-dependent burst generation in neuroendocrine Dahlgren cells in
      the teleost Platichthys flesus.
AB  - The neuroendocrine Type 1 Dahlgren cells of the caudal neurosecretory system of
      the flounder display characteristic bursting activity, which may increase
      secretion efficiency. The firing activity pattern in these cells was voltage
      dependent; when progressively depolarized, cells moved from silent (approximately
      -70 mV), through bursting and phasic to tonic firing (< -65 mV). Brief (10 s)
      evoked bursts of spikes were followed by a slow after-depolarization (ADP;
      amplitude up to 10 mV, duration 10-200 s), which was also voltage-dependent and
      could trigger a prolonged burst. The ADP was significantly reduced in the absence
      of external Ca(2+) ions or the presence of the L-type Ca(2+) channel blocker,
      nifedipine. BayK 8644 (which increases L-type channel open times) significantly
      increased ADP duration, whereas the Ca(2+)-activated nonselective cation channel
      blocker, flufenamic acid, had no effect. Pharmacological blockade of Ca(2+)
      activated K(+) channels, using apamin and charybdotoxin, increased the duration
      of both ADP and evoked bursts. However, action potential waveform was unaffected
      by either apamin/charybdotoxin, nifedipine, BayK 8644 or removal of external
      Ca(2+). The short duration (approximately 100 ms), hyperpolarization-activated,
      postspike depolarizing afterpotentials (DAP), were significantly reduced by
      nifedipine. We propose that long duration ADPs underlie bursts and that short
      duration DAPs play a role in modulation of spike frequency.

PMID- 15500544
TI  - Central neuropeptide B administration activates stress hormone secretion and
      stimulates feeding in male rats.
AB  - Neuropeptide B (NPB) was identified to be an endogenous, peptide ligand for the
      orphan receptors GPR7 and GPR8. Because GPR7 is expressed in rat brain and, in
      particular, in the hypothalamus, we hypothesized that NPB might interact with
      neuroendocrine systems that control hormone release from the anterior pituitary
      gland. No significant effects of NPB were observed on the in vitro releases of
      prolactin, adrenocorticotropic hormone (ACTH) or growth hormone (GH) when log
      molar concentrations ranging from 1 pM to 100 nM NPB were incubated with
      dispersed anterior pituitary cells harvested from male rats. In addition NPB (100
      nM) did not alter the concentration response stimulation of prolactin secretion
      by thyrotropin-releasing hormone, ACTH secretion by corticotropin-releasing
      factor (CRF) and GH secretion by GH-releasing hormone. However, NPB, when
      injected into the lateral cerebroventricle (i.c.v.) of conscious, unrestrained
      male rats, elevated prolactin and corticosterone, and lowered GH levels in
      circulation. The threshold dose for the effect on corticosterone and prolactin
      levels was 1.0 nmol, while that for the effect on GH release was 3.0 nmol NPB.
      Pretreatment with a polyclonal anti-CRF antiserum completely blocked the ability
      of NPB to stimulate ACTH release and significantly inhibited the effect of NPB on
      plasma corticosterone levels. NPB administration i.c.v. did not significantly
      alter plasma vasopressin and oxytocin levels in conscious rats. It did stimulate
      feeding (minimum effective dose 1.0 nmol) in sated animals in a manner similar to
      that of the other endogenous ligand for GPR7, neuropeptide W. We conclude that
      NPB can act in the brain to modulate neuroendocrine signals accessing the
      anterior pituitary gland, but does not itself act as a releasing or inhibiting
      factor in the gland, at least with regard to prolactin, ACTH and GH secretion.

PMID- 15500545
TI  - Central and peripheral administration of kisspeptin-10 stimulates the
      hypothalamic-pituitary-gonadal axis.
AB  - Kisspeptin is the peptide product of the KiSS-1 gene and the endogenous agonist
      for the GPR54 receptor. Recent evidence suggests the kisspeptin/GPR54 system is a
      key regulator of the reproductive system. We examined the effect of
      intracerebroventricular (i.c.v.) and peripheral administration of the active
      kisspeptin fragment, kisspeptin-10, on circulating gonadotrophins and total
      testosterone levels in adult male rats. The effect of kisspeptin-10 in vitro on
      the release of hypothalamic peptides from hypothalamic explants and
      gonadotrophins from anterior pituitary fragments was also determined. The i.c.v.
      administration of kisspeptin-10 dose-dependently increased plasma luteinizing
      hormone (LH) and increased plasma follicle stimulating hormone (FSH) and total
      testosterone at 60 min postinjection. In a separate study investigating the time
      course of this response, i.c.v. administered kisspeptin-10 (3 nmol) significantly
      increased plasma LH at 10, 20 and 60 min, FSH at 60 min and total testosterone at
      20 and 60 min postinjection. Kisspeptin-10 stimulated the release of luteinizing
      hormone-releasing hormone (LHRH) from in vitro hypothalamic explants. Peripheral
      administration of kisspeptin-10 increased plasma LH, FSH and total testosterone.
      However, doses of 100-1000 nM kisspeptin-10 did not influence LH or FSH release
      from pituitary fragments in vitro. Kisspeptin therefore potently stimulates the
      hypothalamic-pituitary-gonadal axis. These effects are likely to be mediated via
      the hypothalamic LHRH system.

PMID- 15500546
TI  - The roles of dopamine and the neurointermediate lobe of the pituitary in the
      regulation of prolactin secretion during late pregnancy in rats.
AB  - The major hypothalamic control over prolactin secretion from the anterior
      pituitary gland is inhibitory by means of dopamine released from
      tuberoinfundibular dopamine (TIDA) neurones. We have previously shown a
      dissociation between activity of TIDA neurones and prolactin secretion during
      late pregnancy, suggesting involvement of additional regulatory factors. The aim
      of the present study was to investigate the role of dopamine and the
      neurointermediate lobe (NIL) of the pituitary in the regulation of prolactin
      secretion during late pregnancy. To determine whether dopamine maintains
      inhibition of prolactin during late pregnancy, the D(2) receptor antagonist
      domperidone was administered at 12.00 h on days 18 and 21 of pregnancy. These
      times are characterized by high and low TIDA neuronal activity, respectively, and
      low prolactin secretion. Domperidone produced an immediate increase in plasma
      prolactin compared to vehicle-treated controls on both days 18 and 21. Thus,
      dopaminergic inhibition of prolactin secretion is maintained despite reduced TIDA
      neuronal activity at the end of pregnancy. The contribution of NIL-derived
      dopamine in regulating prolactin secretion was then examined by investigating the
      effect of surgical removal of the NIL. NIL removal produced significantly
      increased basal prolactin concentrations, indicating that dopamine from the NIL
      contributes to the suppression of prolactin before the antepartum prolactin
      surge. Furthermore, NIL removal also completely prevented the antepartum
      prolactin surge compared to sham-operated controls, which is consistent with the
      hypothesis that the NIL supplies a prolactin-releasing factor to the anterior
      pituitary to induce the antepartum prolactin surge.

PMID- 15500547
TI  - Environmental oestrogens: foe or friend?
AB  - Oestrogens act throughout the body and are important "shapers" of development,
      including of brain sexual differentiation. This has raised concern that
      environmental oestrogens could affect such processes. However, experience with
      studies of the male reproductive tract suggests that most environmental
      oestrogens are too weak to pose such a threat. Conversely, as emerging data
      suggest that oestrogens have health-beneficial effects on the brain, could
      environmental oestrogens actually be good for us?

PMID- 15500548
TI  - Inhibition of subgenomic hepatitis C virus RNA in Huh-7 cells: ribavirin induces
      mutagenesis in HCV RNA.
AB  - Hepatitis C virus (HCV) infection is a major problem throughout the world.
      Combination therapy of interferon (IFN) and ribavirin is the best treatment for
      eradication at present, but the mechanism is not completely understood. We used
      the HCV replicon system to investigate this mechanism. The effects of six drugs
      (UDCA, glycyrrhizin, TJ-9, bezafibrate, ribavirin, and alpha-IFN 2b) on HCV
      subgenomic RNA (genotype 1b, NS5B 415Y) were examined by reverse transcription
      polymerase chain reaction, cloning and sequencing. The HCV replication was
      inhibited by alpha-IFN 2b (7.39-13.2% at 10 U/mL, 3.29-6.12% at 100 U/mL, 1.3
      4.86% at 1000 U/mL) and by ribavirin (4.36-13.9% at 100 microg/mL), but not by
      the other drugs at 24-72 h after treatment. Furthermore, the combination
      treatment was superior to IFN monotherapy and to ribavirin monotherapy at 72 h
      post-treatment. Sequence analyses of the double-stranded RNA-activated protein
      kinase (PKR)-binding domain and flanking regions within the HCV NS5A region
      revealed that the total numbers of substitutions caused by ribavirin (n = 36) or
      combination treatment (n = 57) were more than those of IFN alone (n = 5) and
      controls (n = 6). The HCV replicon system is the most efficient system for HCV
      replication and is an excellent choice for testing anti-HCV drugs and
      disinfectants. Our results further suggested that the combination of alpha-IFN 2b
      and ribavirin might induce mutations, and inhibit HCV RNA synthesis in
      hepatocytes to a greater extent than ribavirin monotherapy.

PMID- 15500550
TI  - High levels of p53 protein expression do not correlate with p53 mutations in
      hepatocellular carcinoma.
AB  - To determine the relationship between p53 altered expression and p53 mutations in
      hepatocellular carcinoma (HCC), we analysed p53 protein immunohistochemically and
      assessed the presence of mutations in exons 4-8 of the p53 gene using SSCP assay
      in 117 HCCs corresponding to 78 patients. We also determined the relationship of
      p53 expression with cellular proliferation by immunostaining with monoclonal
      antibodies to Ki-67. We found significant levels of p53 protein expression in
      23.1% of the 117 cases studied, but identified mutations in only 12 cases
      (10.3%). Only four of the p53-positive cases had mutations in the regions
      analysed. Six of the cases that displayed mutations at p53 gene were negative for
      immunohistochemical analysis (IHC) and two cases showed positive immunoreactivity
      in the cytoplasm of the cell. In conclusion, strong IHC reactivity for p53
      protein is not an indicator of the presence of p53 gene mutations at exons 4-8 in
      HCC. Thus, p53 loss of function in HCC should be evaluated both by p53 mutation
      analysis and p53 protein expression, as both give complementary information about
      p53 status.

PMID- 15500549
TI  - HBV core sequence: definition of genotype-specific variability and correlation
      with geographical origin.
AB  - There are eight genotypes and nine subtypes of HBV. Small differences in
      geographical origin are associated with sequence changes in the surface gene.
      Here, we compared core gene sequences from different genotypes and geographical
      regions. Specific combinations of 24 amino acid substitutions at nine residues
      allowed allocation of a sequence to a subtype. Six of these nine residues were
      located in different T cell epitopes depending on HBV geographical area and/or
      genotype. Thirty-seven nucleotide changes were associated uniquely with specific
      genotypes and subtypes. Unique amino acid and nucleotide variants were found in a
      majority of sequences from specific countries as well as within subtype ayw2 and
      adr. Specific nucleotide motifs were defined for Korean, Indian, Chinese, Italian
      and Pacific region isolates. Finally, we observed amino acid motifs that were
      common to either South-east Asian or Western populations, irrespective of
      subtype. We believe that HBV strains spread within constrained ethnic groups,
      result in selection pressures that define sequence variability within each
      subtype. It suggests that particular T cell epitopes are specific for
      geographical regions, and thus ethnic groups; this may affect the design of
      immunomodulatory therapies.

PMID- 15500551
TI  - Negative correlation between intrahepatic expression of hepatitis C antigens and
      apoptosis despite high-level expression of Fas and HLA antigens.
AB  - The role of virus-related apoptosis in hepatic injury in chronic HCV is unclear.
      It is unknown whether HCV induces apoptosis directly or whether cellular injury
      is immunologically mediated. We studied the relationship between infected
      hepatocytes, apoptosis and necroinflammation. We established a Fluorescence
      Activated Cell Sorter (FACS) based intracellular staining technique for the HCV
      NS3 protein and examined intrahepatic viraemia, disease activity and apoptosis.
      We also stained infected cells for expression of human leucocyte antigen (HLA)
      class I and Fas antigens. We examined 34 liver biopsies (24 from patients with
      HCV) and found marked variation in the proportion of infected cells (2.5-42%).
      The number of infected cells correlated with serum viraemia but not histology.
      The number of infected cells was inversely related to the number of apoptotic
      cells (P < 0.001); infected cells expressed both HLA class I (14 cases) and Fas
      antigens (12 cases). The number of hepatocytes infected with hepatitis C is
      variable and does not influence histological activity. In infected patients, the
      majority of HCV-positive hepatocytes express target molecules for activated
      lymphocytes (Fas and HLA class I antigens) but they do not undergo apoptosis,
      suggesting that hepatitis C may inhibit apoptosis by modulating intracellular pro
      apoptotic signals.

PMID- 15500552
TI  - Binding of HCV E2 to CD81 induces RANTES secretion and internalization of CC
      chemokine receptor 5.
AB  - Hepatitis C virus (HCV) infection has been shown to be associated with reduced
      expression of the CC chemokine receptor (CCR) 5, and reduced responsiveness of
      lymphocytes to chemokines. However, the mechanism by which HCV alters CCR5
      expression remains unclear. Here, we investigated whether altered CCR5 expression
      in hepatitis C results from interactions of CD81 with the HCV E2 protein.
      Peripheral blood mononuclear cells (PBMC) from HCV-negative individuals were
      prepared by Ficoll density gradient separation. PBMC subpopulations (CD4+, CD8+
      lymphocytes, CD19+ B cells, natural killer (NK) cells and monocyte-derived
      dendritic cells) were isolated and stimulated with immobilized HCV E2, and
      changes in CCR5 expression and CC-chemokine secretion were determined. Migration
      assays were performed using a 5-microm nitrocellulose filter microchamber system
      according to the manufacturer's recommendations. Exposure of PBMC to HCV E2
      induced a dose-dependent release of regulated on activation normal T-cell
      expressed and secreted (RANTES), down-regulation of CCR5 expression and
      intracellular accumulation of CCR5. This effect was blocked by preincubation of
      PBMC with anti-CD81. RANTES release following exposure to HCV E2 was mainly
      attributable to CD8+ cells. After exposure to HCV E2 markedly fewer CD8-positive
      lymphocytes were attracted by RANTES when compared with CD8+ cells that were
      studied in the absence of HCV E2. Our results suggest that interaction of HCV E2
      with CD81 leads to increased RANTES secretion by CD8+ lymphocytes which induces
      down-regulation of CCR5 surface via receptor internalization resulting in altered
      lymphocyte migration.

PMID- 15500553
TI  - Hepatitis C virus infection in asymptomatic male volunteer blood donors in
      Karachi, Pakistan.
AB  - The objectives of this study were to assess the proportion of hepatitis C virus
      (HCV) reactors and to identify risk factors associated with HCV infection in
      volunteer blood donors in Karachi, Pakistan. Between 1 January 1998 and 31
      December 2002, consecutive blood donations tested at two blood banks were used to
      assess the proportion of HCV sero-reactors donors. To evaluate the potential risk
      factors, a case-control study design was implemented to select cases and controls
      between 15 October 2001 and 15 March 2002. The overall seroprevalence of HCV in
      these blood donors was 1.8% (6349/35 1309). Trend analysis revealed a significant
      (P < 0.001) linear increase in proportions of HCV-seropositive donors from 1998
      to 2002. Final multivariate logistic regression model showed that the cases were
      more likely than controls to have reported past hospitalization or to have
      received multiple injections. When a glass syringe was used to give therapeutic
      injections, it increased the adjusted odds of being HCV seropositive
      significantly more among cases than in controls and this relationship was
      stronger when injection was given by general medical practitioner than if the
      injection was given in hospital setting. Cases were more likely than controls to
      have reported sexual contact with multiple sexual partners. Primary prevention
      programmes focused on identified risk factors might help to curtail the spread of
      HCV infection in this community and in other similar settings in developing
      countries.

PMID- 15500554
TI  - Treatment of patients with HCV infection with or without liver biopsy.
AB  - Expert consensus recommends liver biopsy before therapy for chronic hepatitis C.
      A cost effectiveness analysis suggested that the best strategy in the management
      of patients was to treat without biopsy. We compared therapy in patients who did,
      or did not undergo biopsy. Hepatitis C virus (HCV)-positive patients (78) who did
      not agree to (n = 57) or with contraindications to liver biopsy (n = 21) (group
      A) were matched for age, sex and genotype with those who consented (group B).
      Before therapy (interferon/ribavirin for 12 months), a clinical diagnosis of
      chronic hepatitis, on the basis of standard biochemical and ultrasonographic
      parameters. The two groups showed similar baseline characteristics. A
      noninvasive, diagnosis of chronic hepatitis was made in 75.6% of group A, and in
      83.3% of group B (P = 0.26). Concordance between clinical and histological
      diagnosis in group B amounted to 91%. End-of-therapy virological response was
      52.6% in group A, and 57.7% in group B (P = 0.63). Sustained virological response
      was 41.0% [95% confidence interval (CI) 30.1-51.9] and 43.6% (95% CI 32.6-54.6)
      in the two groups (P = 0.87). Predictors of sustained response were noninvasive
      diagnosis of chronic hepatitis (P = 0.006), lack of portal hypertension (P =
      0.037), platelets >10(5)/mm3 (P = 0.007), prothrombin >70% (P = 0.02), and
      genotype 2 or 3 (P < 0.0001). At multivariate analysis, genotype (P < 0.0001) and
      platelets (P = 0.004) maintained their predictive power. In most patients with
      HCV infection, virological clearance after therapy can be achieved irrespective
      of whatever a liver biopsy might show.

PMID- 15500555
TI  - A randomized trial of prolonged high dose of interferon plus ribavirin for
      hepatitis C patients nonresponders to interferon alone.
AB  - Retreatment of chronic hepatitis C patients nonresponders to interferon (IFN)
      alone with the standard dose of IFN [3 million units (MU) thrice weekly (TIW)]
      plus ribavirin for 24 weeks has yielded low sustained virological response (SVR),
      averaging 8%. The aim of the present, open-labelled, randomized study was to
      evaluate the efficacy of IFN induction therapy followed by prolonged high dose of
      IFN plus ribavirin in nonresponders. One hundred and fifty-one patients were
      randomized to receive 5 MU daily of IFN alfa-2b (group 1, n = 73) or 5 MU TIW of
      IFN alfa 2b (group 2, n = 78) for 4 weeks followed by IFN (5 MU TIW) plus
      ribavirin (1000/1200 mg/daily) for 48 weeks in both groups. In an intention-to
      treat analysis, the sustained virological response (SVR) at 24-week follow-up was
      33 and 23% for group 1 and 2, respectively (P = 0.17). The overall SVR was 52 and
      18% in patients with genotype 2/3 and 1/4, respectively. Among genotype 1/4
      patients the SVR was 29 and 11% for age younger or older than 40 years. Compared
      with genotype 2/3 patients, the risk (95% confidence interval) of nonresponse to
      retreatment was 3.0-fold (1.17-8.0) in younger genotype 1/4 patients and 8.4-fold
      (3.0-23.29) in older genotype 1/4 patients. In conclusion these results suggest
      that retreatment with a reinforced regimen should be focused in nonresponder
      genotype 2/3 patients and younger genotype 1/4 patients, who are most likely to
      benefit. Induction therapy does not improve SVR.

PMID- 15500556
TI  - Beneficial effects of 'lamivudine pulse' therapy in HBeAg-positive patients with
      normal ALT*.
AB  - Currently no therapy is given to patients with chronic hepatitis B virus (HBV)
      infection who are HBeAg positive with normal alanine aminotransferase (ALT)
      levels. Steroid priming has been shown to enhance T-helper-1 (Th-1) cell
      response. Lamivudine may restore immunologic competence against HBV by causing a
      sudden decline in the level of the virus. We examined the efficacy of lamivudine
      pulse therapy on the seroconversion from HBeAg to anti-HBe. This was a
      prospective single-blinded trial including 27 patients with chronic hepatitis B,
      HBeAg positive with ALT < or =1.5 times upper limit of normal (ULN). Lamivudine
      was administered initially for 4 weeks, then stopped for 2 weeks and later
      restarted and continued till 3 months after seroconversion or completion of 2
      years of therapy. Twenty-six patients completed the study. Lamivudine withdrawal
      led to a rise in ALT levels above the ULN in 11 (42.3%) patients at 6 weeks;
      seven of them (63.6%) lost HBeAg compared with only two of the 15 patients
      (13.3%), in whom ALT levels did not rise (P = 0.011). As one patient showed a
      relapse, a total of eight (31%) patients responded to lamivudine pulse therapy
      over a mean period of 17.3 +/- 4.5 months. Responders had a higher serum albumin
      (P < 0.05), a lower fibrosis score (P < 0.05), and a relatively high baseline
      serum ALT levels (P = 0.024) than the nonresponders. YMDD mutations developed in
      three patients and none responded. No patient developed hepatic decompensation.
      Hence lamivudine pulse therapy has potential in converting HBeAg-positive, 'not
      treat-worthy' (ALT < 1.5 ULN) patients to treat-worthy (ALT > 1.5 ULN) in 42%,
      with sustained HBeAg and HBV DNA loss in 31% patients. The effects are possibly
      because of a combination of antiviral and immunomodulating activities of
      lamivudine.

PMID- 15500557
TI  - Survival in HIV-infected patients is associated with hepatitis C virus infection
      and injecting drug use since the use of highly active antiretroviral therapy in
      the Lyon observational database.
AB  - Highly active antiretroviral therapy (HAART) has reduced the incidence of death
      in HIV-infected patients but various rates of survival have been reported due to
      the infection with hepatitis C virus (HCV) and the use of injecting drugs (IDU).
      A survival analysis was performed to estimate and compare the death rates in HIV
      positive patients infected by IDU and/or positive for HCV antibodies in the pre
      HAART and HAART periods in Lyon (France) between 1992 and 2002. Patients were
      stratified into four groups (G): HCV-/IDU-(G1), HCV+/IDU-(G2), HCV+/IDU-(G3),
      HCV+/IDU+ (G4) and adjusted death rates in the pre-HAART era (< 1996) and the
      HAART era (> or = 1996) were compared. The aHR of progression to death was 1.05
      (95% CI 0.75-1.47, P = 0.75) for G2, 1.09 (95% CI 0.54-2.22, P = 0.81) for G3 and
      0.90 (95% CI 0.65-1.24, P =0.51) for G4 compared with G1 in the pre-HAART era.
      The aHR of progression to death was 0.76 (95% CI 0.28-2.08, P = 0.59) for G2,
      1.23 (95% CI 0.17-8.86, P = 0.84) for G3 and 2.90 (95% CI 1.62-5.20, P < 0.001)
      for G4, compared with G1 in the HAART era. HAART management of HCV+/IDU+ patients
      needs to be optimized for them to achieve a similar benefit as observed among
      other individuals.

PMID- 15500558
TI  - Is it possible to diagnose acute hepatitis C virus (HCV) infection by a rising
      anti-HCV titre rather than by seroconversion?
AB  - The diagnosis of acute hepatitis C virus (HCV) infection relies on documented
      positive-seroconversion of HCV antibody (anti-HCV). Because of the detection of
      seroconversion at an earlier stage by second or third generation anti-HCV enzyme
      immunoassays (EIA), the diagnosis of acute hepatitis C (AHC) may be
      underestimated. The aim of this study was to evaluate whether rising anti-HCV
      titre could be used to diagnose AHC or not. Eighteen patients with a clinical
      diagnosis of acute hepatitis C were enrolled, including eight cases with
      documented seroconversion to anti-HCV and 10 cases with clinically suspected
      acute hepatitis C. Four chronic hepatitis C patients with acute exacerbation were
      selected as a control group. Serial sera were assayed with a third generation
      anti-HCV (AxSYM, version 3.0; Abbott, Chicago, IL, USA) and recombinant
      immunoblot assays (RIBA; Chiron HCV 3.0 Strip; Immunoblot, Emeryville, CA, USA)
      and the titre of anti-HCV expressed as signal/cutoff (S/CO) ratio and the RIBA
      patterns were correlated. Seven of eight documented AHC (one lacking the initial
      serum) and five of 10 clinically suspected AHC showed a rising pattern of S/CO
      values. The initial S/CO values on the first visit were less than 40 in 14 of 18
      cases. The RIBA pattern shifted from negative/indeterminate to positive in five
      of seven documented AHC and 4 of 10 clinically suspected AHC cases. Fifteen of 18
      cases had seroconversions of at least one antibody, whilst 85.7% showed a rising
      S/CO ratio. On the contrary, the S/CO ratio and RIBA pattern remained unaltered
      in chronic hepatitis C with acute exacerbation. The rise in S/CO was usually
      accompanied with an increase in the number of RIBA reactive bands and their
      intensity in acute hepatitis C patients. The rise in S/CO ratios using a third
      generation anti-HCV assay and the RIBA pattern might be used as a supplemental
      diagnostic criterion for acute HCV infection.

PMID- 15500559
TI  - Spontaneous clearance of hepatitis C virus after long-term opiate dependence
      therapy with buprenorphine.

PMID- 15500562
TI  - Therapeutic implications of the MDR-1 gene.
AB  - Drug transporters significantly influence drug pharmacokinetics and
      pharmacodynamics. P-glycoprotein (P-gp), the product of the MDR1 (ABCB1) gene, is
      among the most well-characterized drug transporters, particularly in veterinary
      medicine. A number of clinically relevant, structurally and functionally
      unrelated drugs are substrates for P-gp. P-gp is expressed by a variety of normal
      tissues including the intestines, renal tubular cells, brain capillary
      endothelial cells, biliary canalicular cells, and others, where it functions to
      actively extrude substrate drugs. In this capacity, P-gp limits oral absorption
      and central nervous system entry of many substrate drugs. A number of MDR1
      polymorphisms have been described in human patients, some of which result in
      altered drug pharmacokinetics and susceptibility to diseases such as Parkinson's
      disease, inflammatory bowel disease, refractory seizures, and others. An MDR1
      polymorphism in herding breed dogs, including collies and Australian shepherds,
      has been demonstrated to be the cause of ivermectin sensitivity in these breeds.
      Recent evidence suggests that this polymorphism, a 4-bp deletion mutation,
      results in increased susceptibility to the toxicity of several drugs in addition
      to ivermectin. Furthermore, data in rodent models suggest that P-gp may play an
      important role in regulating the hypothalamic-pituitary-adrenal axis.

PMID- 15500563
TI  - Angiotensin-converting enzyme inhibitors in the therapy of renal diseases.
AB  - Renal diseases, especially chronic renal failure (CRF), are common in canine and
      feline medicine. The renin-angiotensin-aldosterone system (RAAS) plays a pivotal
      role in these conditions in the development of renal lesions and the progression
      of kidney dysfunction. Angiotensin-converting enzyme inhibitors (ACEI) are
      currently considered as the most efficient agents in therapeutic strategies. The
      benefit of an ACEI treatment can be explained by at least three mechanisms: ACEI
      limit systemic and glomerular capillary hypertension, have an antiproteinuric
      effect, and retard the development of glomerulosclerosis and tubulointerstitial
      lesions. These effects have been studied in dogs and cats, and there is now some
      evidence to support the recommendation of ACEI therapy in dogs and cats with CRF.
      Nevertheless the prescription of ACEI in such patients should take into account
      the potential influence of renal impairment on ACEI disposition, and adverse
      effects on the renal function itself (especially hypotension and acute reductions
      in glomerular filtration rate). The risk of drug interaction with diuretics,
      nonsteroidal anti-inflammatory drugs and anesthetics, should not be
      overestimated. Furthermore, hypotension may occur in patients on a low sodium
      diet.

PMID- 15500564
TI  - Population pharmacokinetics of marbofloxacin in horses: preliminary analysis.
AB  - Population pharmacokinetic of marbofloxacin was investigated on 21 healthy and 16
      diseased horses to assess interindividual variability of drug exposure.
      Demographic, physiologic and disease covariables were tested using mixed effects
      models. As a preliminary analysis, this study has demonstrated that none of the
      tested covariables were significant in regression models for compartmental
      volumes or clearance of distribution, but the clinical status of the horse
      (healthy/diseased) was a significant covariable (P < 0.01) for systemic
      clearance. Clearance had a lower mean and a higher variance for diseased horses
      than healthy horses, with respectively a mean of 0.209 and 0.284 L/h/kg and a
      coefficient of variation of 52 and 15%. Consequently, variability of AUC was
      greater in diseased horses. Considering an AUC/MIC ratio below 60 h as a
      prediction of poor efficacy, a dosage regimen of 2 mg/kg intravenous was deemed
      to be inadequate for 19% of diseased horses if the MIC of the bacteria was 0.1
      microg/mL. However 93% of diseased horses could achieve a ratio above 125 h,
      predicting a very good efficacy, for the MIC(90) of Enterobacteriacae (0.027
      microg/mL).

PMID- 15500565
TI  - Pharmacokinetics of florfenicol in North American elk (Cervus elaphus).
AB  - Florfenicol pharmacokinetics after administration of a single subcutaneous (s.c.)
      dose of 40 mg/kg of body weight in adult elk (Cervus elaphus) was investigated.
      Serum florfenicol concentrations were determined by a sensitive high-performance
      liquid chromatographic method with limit of quantification of 0.03 microg/mL.
      Florfenicol pharmacokinetic parameters in elk were estimated using a
      noncompartmental approach. After a single s.c. injection, florfenicol
      concentrations remained above 1 microg/mL for approximately 36 h and above 0.5
      microg/mL for approximately 72 h. Following s.c. injection, florfenicol was
      absorbed rapidly with a mean maximum concentration (C(max)) of 3.7 microg/mL
      achieved at 4.2 h (T(max)). The C(max) value in elk is similar to values reported
      in cattle at the same dose, suggesting that the 40 mg/kg s.c. dose achieves
      therapeutic concentrations in elk. A mean elimination half-life (t(1/2)) of 44 h
      is shorter than that reported in cattle. The more rapid elimination half-life in
      elk suggests that elk may require a multiple dose regimen for therapeutic success
      with s.c. Nuflor. We recommend s.c. Nuflor be administered subcutaneously to elk
      every 24 h at a dose level of 40 mg/kg.

PMID- 15500566
TI  - Cefotaxime kinetics in plasma and synovial fluid following intravenous
      administration in horses.
AB  - Cefotaxime powder was diluted with sterile water to a concentration of 100 mg/mL.
      The volume of solution was adjusted for each experimental horse to provide a
      total dose of 15, 20, and 25 mg/kg and was administered by infusion through a
      jugular vein catheter over a 10-min period. All three doses were administered to
      each of the six experimental horses at three different times. Cefotaxime
      concentrations in plasma and synovial fluid samples were measured by high
      performance liquid chromatography (HPLC). Standard compartmental analysis
      techniques and the WinSAAM modeling program were used to determine standard
      pharmacokinetic parameters for cefotaxime. The plasma and synovial fluid data
      from the five horses administered the 25 mg/kg dose was analyzed. Plasma
      cefotaxime concentrations appeared to be linearly related to dose infused and
      declined in parallel, suggesting linear drug kinetics. Moreover, cefotaxime
      concentrations declined monotonically suggesting that its disposition kinetics
      could essentially be described by a one-compartment model rather than the fact
      that sampling occurred after the infusion was discontinued. Maximum concentration
      of cefotaxime in plasma occurred immediately after cessation of the infusion.
      Minimum inhibitory concentrations were determined for Staphylococcus aureus,
      Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae, common
      isolates from septic arthritis in horses. Based on our pharmacokinetic data, a
      regimen of 25 mg/kg administered i.v. every 6 h appears appropriate for
      susceptible joint infections in adult horses.

PMID- 15500567
TI  - Integrated pharmacological assessment of flubendazole potential for use in sheep:
      disposition kinetics, liver metabolism and parasite diffusion ability.
AB  - Flubendazole (FLBZ) is a broad spectrum benzimidazole methylcarbamate
      anthelmintic widely used in poultry and swine. However, there is no information
      available on the pharmacological behaviour of FLBZ in ruminants. The work
      reported here was addressed to evaluate the potential of FLBZ for use in sheep.
      The integrated assessment included evaluation of FLBZ and metabolites plasma
      disposition kinetics, liver metabolism and ex vivo ability to diffuse into the
      cestode parasite Moniezia benedeni. In a cross-over kinetic study, six healthy
      Corriedale sheep were treated with FLBZ by intravenous (i.v.) (4% solution) and
      intraruminal (i.r.) (4% suspension) administrations at the same dosage (5 mg/kg)
      with a 21-day washout period between treatments. Blood samples were collected
      between 0 and 72 h post-treatments. Sheep liver microsomes were incubated with 40
      microm FLBZ and specimens of the cestode parasite M. benedeni, collected from
      untreated animals, were incubated (5-120 min) with FLBZ and its reduced (R-FLBZ)
      metabolite (5 microm). Samples of plasma, microsomal incubations and parasite
      material were prepared and analyzed by high-performance liquid chromatography to
      measure FLBZ and its metabolites. FLBZ parent drug showed a fast disposition
      being detected in the bloodstream up to 36 h after its i.v. administration. Both
      R-FLBZ and hydrolyzed FLBZ (H-FLBZ) metabolites were recovered in plasma as early
      as 5 min after the i.v. treatment in sheep. The plasma AUC ratios for R-FLBZ and
      FLBZ (AUC(R-FLBZ)/AUC(FLBZ)) were 4.07 i.v. and 5.55 i.r., respectively. R-FLBZ
      achieved a significantly higher (P < 0.01) C(max) value (0.14 microg/mL at 17.3 h
      post-treatment) than that observed for the parent drug FLBZ (0.04 microg/mL at
      14.4 h post-treatment). Low plasma concentrations of FLBZ parent drug were
      measured between 6 and 48 h, and only trace concentrations of H-FLBZ were
      detected during a short period of time after the i.r. treatment. Consistently,
      sheep liver microsomes metabolized FLBZ into its reduced metabolite at a rate of
      9.46 +/- 2.72 nmol/mg/h. Both FLBZ and R-FLBZ demonstrated a similar ability to
      quickly diffuse through the tegument of the cestode parasite. The data on FLBZ
      pharmacological behaviour presented here contribute to evaluate its potential to
      be developed as an anthelmintic for broad spectrum parasite control in ruminants.

PMID- 15500568
TI  - Aspects of pharmacodynamics and biotransformation of the glucocorticoid
      resocortol butyrate.
AB  - Aspects of the biotransformation and pharmacodynamics of the novel glucocorticoid
      resocortol butyrate (RCB) and its metabolites were assessed in vitro and in vivo
      in comparison with selected reference compounds. The main route of
      biotransformation of ((3)H)-RCB in the skin and the liver was 5alpha-reduction of
      the A-ring followed by reduction of the 3-carbonyl group. In the liver,
      metabolism was much more rapid than in the skin and 5beta-reduction also
      occurred. RCB had a relative binding affinity for the glucocorticoid receptor
      similar to that of triamcinolone acetonide, about 1.5 times that of
      dexamethasone, three times that of betamethasone valerate (BMV) and 10-14 times
      that of cortisol. The metabolites of RCB displayed only low to very low
      affinities for the receptor. The suppression of the hypothalamic-pituitary
      adrenal axis was investigated in placebo- and positive-controlled studies in dogs
      by measurement of basal and corticotrophin-releasing hormone (CRH) stimulated
      plasma cortisol concentrations. The AUC of the plasma cortisol vs. time curve
      following CRH stimulation, a measure of adrenal suppression, was reduced
      significantly after topical application of BMV compared with the pretreatment
      values. The AUC in the RCB group was not reduced significantly.
      Adrenocorticotrophic hormone concentrations were not affected. Oral
      administration of RCB did not suppress adrenocortical function, whereas BMV
      induced almost complete suppression of basal and CRH-induced cortisol
      concentrations. The pharmacodynamics of RCB makes it a relatively safe
      glucocorticosteroid for topical application.

PMID- 15500569
TI  - Clinical efficacy of carprofen as an adjunct to the antibacterial treatment of
      bovine respiratory disease.
AB  - A clinical trial was undertaken to investigate the efficacy of a single dose of
      carprofen (CPF) in the treatment of bovine respiratory disease in cattle.
      Tilmicosin was used as a basal treatment in all animals. Six hours after dosing,
      body temperature and respiratory rates in animals treated with CPF-tilmicosin had
      decreased and were significantly lower than in the animals treated with
      tilmicosin alone (P < 0.05). Over the period of clinical observation, CPF
      tilmicosin treatment produced a clinical resolution of the pneumonia similar to
      treatment with tilmicosin alone. However, it is significant from an animal
      welfare perspective that over the period of the study after treatment, CPF
      tilmicosin therapy produced significantly greater symptomatic improvement than
      tilmicosin.

PMID- 15500570
TI  - Evaluation of dexamethasone for the treatment of intracerebral hemorrhage using a
      collagenase-induced intracerebral hematoma model in rats.
AB  - Dexamethasone was evaluated for the treatment of intracerebral hemorrhage using a
      rat model of cerebral hematoma induced by intracerebral injection of collagenase.
      The treatment group consisted of hematoma rats receiving dexamethasone 1 mg/kg
      intraperitoneal (i.p.) at 1 and 24 h following surgery. Controls included
      hematoma rats receiving saline i.p. and sham-operated animals receiving saline
      i.p. Each animal was evaluated neurologically prior to, as well as 24 and 48 h
      following surgery. After the last neurological evaluation, animals were deeply
      anesthetized and the brain was removed following perfusion for microscopic
      examination and glial fibrillary acidic protein immunohistochemistry. Behavioral
      scores were significantly improved in the treated group (P < 0.0001). The
      hematoma volume was significantly smaller (P < 0.02). Neutrophils and astrocytes
      were less numerous in the hematoma of dexamethasone-treated animals (P < 0.001),
      however the number of necrotic neurons in the penumbra was not changed by the
      treatment. The number of necrotic neurons in the cerebral cortex was less in
      treated than in nontreated animals (P < 0.01). Controls had many vascular changes
      including necrotic endothelium and fibrin deposits compared with treated animals.
      In conclusion, dexamethasone administered shortly after an intracerebral hematoma
      appears beneficial for the treatment of this condition.

PMID- 15500571
TI  - Pharmacokinetic and pharmacodynamic evaluation of intravenous hydromorphone in
      cats.
AB  - This study describes the pharmacokinetics of intravenous hydromorphone in cats
      and the simultaneous measurement of antinociceptive pharmacodynamic effects using
      a thermal threshold testing system. Following establishment of a baseline thermal
      threshold, six adult cats were administered 0.1 mg/kg of hydromorphone
      intravenously. Thermal threshold testing and blood collection were conducted
      simultaneously at predetermined time points. Plasma hydromorphone concentrations
      were determined by a liquid chromatographic-mass spectral method and
      pharmacokinetic analysis was performed by nonlinear least squares regression
      analysis. Plasma hydromorphone concentrations declined rapidly over time, and
      were below the limit of quantification of the assay (LOQ = 1.0 ng/mL) by 360 min.
      In contrast, thermal thresholds rose from a pretreatment value of 40.9 +/- 0.65
      degrees C (mean +/- SEM) to instrument cut-out (55 degrees C) within 15 min and
      remained significantly elevated from 15-450 min after treatment. Inspection of
      the data revealed no direct correlation between plasma hydromorphone
      concentrations and the antinociceptive effect of this drug in cats. These
      findings support the importance of conducting pharmacokinetic studies in parallel
      with objective measurements of drug effect.

PMID- 15500572
TI  - Plasma profile and pharmacokinetics of dextromethorphan after intravenous and
      oral administration in healthy dogs.
AB  - Dextromethorphan is an N-methyl-D-aspartate (NMDA) noncompetitive antagonist
      which has been used as an antitussive, analgesic adjunct, probe drug,
      experimentally to attenuate acute opiate and ethanol withdrawal, and as an
      anticonvulsant. A metabolite of dextromethorphan, dextrorphan, has been shown to
      behave pharmacodynamically in a similar manner to dextromethorphan. The
      pharmacokinetics of dextromethorphan were examined in six healthy dogs following
      intravenous (2.2 mg/kg) and oral (5 mg/kg) administration in a randomized
      crossover design. Dextromethorphan behaved in a similar manner to other NMDA
      antagonists upon injection causing muscle rigidity, ataxia to recumbency,
      sedation, urination, and ptyalism which resolved within 90 min. One dog
      repeatedly vomited upon oral administration and was excluded from oral analysis.
      Mean +/- SD values for half-life, apparent volume of distribution, and clearance
      after i.v. administration were 2.0 +/-0.6 h, 5.1 +/- 2.6 L/kg, and 33.8 +/- 16.5
      mL/min/kg. Oral bioavailability was 11% as calculated from naive pooled data.
      Free dextrorphan was not detected in any plasma sample, however enzymatic
      treatment of plasma with glucuronidase released both dextromethorphan and
      dextrorphan indicating that conjugation is a metabolic route. The short half
      life, rapid clearance, and poor bioavailability of dextromethorphan limit its
      potential use as a chronic orally administered therapeutic.

PMID- 15500573
TI  - Meta-analysis of pharmacokinetic data of veterinary drugs using the Food Animal
      Residue Avoidance Databank: oxytetracycline and procaine penicillin G.
AB  - Investigators frequently face the quandary of how to interpret the often times
      disparate pharmacokinetic parameter values reported in the literature. Combining
      of data from multiple studies (meta-analysis) is a useful tool in
      pharmacokinetics. Few studies have explored the use of meta-analysis for
      veterinary species. Even fewer studies have explored the potential strengths and
      weaknesses of the various methods of performing a meta-analysis. Therefore, in
      this study we performed a meta-analysis for oxytetracycline (OTC) and procaine
      penicillin G (PPG) given intramuscularly to cattle. The analysis included 28
      individual data sets from 18 published papers for PPG (288 data points), and 41
      individual data sets from 25 published papers for OTC (489 data points). Three
      methods were used to calculate the parameters. The first was a simple statistical
      analysis of the parameter values reported in each paper. The second method was a
      standard Two-Stage Method (TSM) using the mean concentration vs. time data
      extracted from each paper. The third method was the use of nonlinear mixed effect
      modeling (NMEM) of the concentration vs. time data reported in the various
      papers, treating the mean data as if each set came from an individual animal. The
      results of this evaluation indicate that all three methods generate comparable
      mean parameter estimates for OTC and PPG. The only significant difference noted
      was for OTC absorption half-lives taken from the published literature, a
      difference attributable to the use of an alternative method of parameter
      calculation. The NMEM procedure offers the possibility of including covariates
      such as dose, age, and weight. In this study the covariates did not influence the
      derived parameters. A combination approach to meta-analysis of published mean
      data is recommended, where the TSM is the first step, followed by the NMEM
      approach.

PMID- 15500574
TI  - Multiple oral dosing of ketoconazole influences pharmacokinetics of quinidine
      after intravenous and oral administration in beagle dogs.
AB  - In this study, we investigated the effect of multiple oral dosing of ketoconazole
      (KTZ) on pharmacokinetics of quinidine (QN), a CYP3A substrate with low hepatic
      clearance, after i.v. and oral administration in beagle dogs. Four dogs were
      given p.o. KTZ for 20 days (200 mg, b.i.d.). QN was administered either i.v. (1
      mg/kg) or p.o. (100 mg) 10 and 20 days before the KTZ treatment and 10 and 20
      days after start of KTZ treatment. Multiple oral dosing of KTZ decreased
      significantly alpha and beta, whereas increased t(1/2beta), V(1), and k(a). The
      KTZ treatment also decreased significantly both total body clearance (Cl(tot))
      and oral clearance (Cl(oral)). No significant change in bioavailability was
      observed in the presence of KTZ. Co-administration of KTZ increased C(max) of QN
      to about 1.5-fold. Mean resident time after i.v. administration (MRT(i.v.)), and
      after oral administration (MRT(p.o.)) of QN were prolonged to about twofold,
      whereas mean absorption time (MAT) was decreased to 50%. Volume of distribution
      at steady state (V(d(ss))) of QN was unchanged in the presence of KTZ. These
      alterations may be because of a decrease in metabolism of QN by inhibition of KTZ
      on hepatic CYP3A activity. In conclusion, multiple oral dosing of KTZ affected
      largely pharmacokinetics of QN after i.v. and oral administration in beagle dogs.
      Therefore, KTZ at a clinical dosing regimen may markedly change the
      pharmacokinetics of drugs primarily metabolized by CYP3A with low hepatic
      clearance in dogs. In clinical use, much attention should be paid to concomitant
      administration of KTZ with the drug when given either p.o. or i.v.

PMID- 15500575
TI  - Pharmacokinetics of orally administered pirfenidone in male and female beagles.
AB  - Pirfenidone, a promising antifibrotic agent, was administered orally to dogs at
      0, 40, 140, and 400 mg/kg/day. Serum was collected for pirfenidone assay at 0, 26
      and 39 weeks of treatment. From the pirfenidone concentrations, pharmacokinetic
      parameters were determined for each dog at each treatment interval. The only
      significant differences because of gender were for concentration maxima.
      Unsurprisingly, there were many significant differences because of dose in
      concentration maximum and area under curve (AUC), and significant, positive
      linear correlations of both parameters with dose. There were few significant
      differences in time of maximal concentration and no correlation with dose. The
      mean +/- SE clearances were 1.99 +/- 0.13, 1.64 +/- 0.13 and 1.78 +/- 0.14 L/h/kg
      for doses of 40, 140, and 400 mg/kg, respectively, with no significant
      differences attributable to dose. There was an unexplained pattern in maximal
      concentration and AUC with regard to duration of treatment, with the parameters
      being highest at week 0, lowest at week 26, and intermediate at week 39.
      Clearance had the reverse pattern; time of maximal concentration had no pattern.

PMID- 15500576
TI  - Sedative effects and serum drug concentrations of oxymorphone and metabolites
      after subcutaneous administration of a liposome-encapsulated formulation in dogs.

PMID- 15500578
TI  - Comparison of three arginine-glycine-aspartate-containing peptides as inhibitors
      of equine platelet aggregation.

PMID- 15500577
TI  - Field evaluation of flunixin meglumine in the supportive treatment of caprine
      mastitis.

PMID- 15500579
TI  - Pharmacokinetics of gentamicin and apramycin in turkeys roosters and hens in the
      context of pharmacokinetic-pharmacodynamic relationships.

PMID- 15500580
TI  - A preliminary investigation of the disposition of tilmicosin residues in elk
      tissues and serum.

PMID- 15500581
TI  - Lack of pharmacokinetic interaction between lincomycin and aspirin in healthy
      goats.

PMID- 15500582
TI  - State of the world's alcohol policy.

PMID- 15500583
TI  - An addiction agency's collaboration with the drinks industry: Moo Joose as a case
      study.
AB  - AIM: This paper analyses a partnership between an addiction agency and the drinks
      industry in Australia, with special reference to concerns held by public health
      advocates for such projects. METHOD: Public health anxieties regarding
      collaboration between the drugs sector and the drinks industry are identified. A
      projected partnership between the Alcohol and Drug Foundation--Queensland (ADFQ)
      and the liquor industry in Australia is reviewed. The partnership involves the
      creation of a new organization, Alcohol Education Australia Ltd. (AEA), which
      states as its aim the education of consumers in responsible drinking. In order to
      assess the impact of the partnership an examination is undertaken of the AEA's
      stated mission and objectives, of relevant policy development by ADFQ and of
      ADFQ's intervention in support of an alcohol manufacturer which was putting a
      case to a licensing authority. FINDINGS: The results indicate the partnership
      advances the interests of the drinks industry rather than public health. The
      mission and objectives of Alcohol Education Australia Ltd subordinate public
      health goals to industry aims and the host organization, the ADFQ, has changed
      its policy and practice to accommodate the drinks industry. CONCLUSION: The
      partnership between the ADFQ and the drinks industry indicates the difficulty
      faced by addiction organizations in maintaining an uncompromising public health
      orientation when in partnership with the alcohol industry.

PMID- 15500584
TI  - The how but not the why; more context needed.

PMID- 15500585
TI  - The beverage alcohol industry's social aspects organizations: a public health
      warning.

PMID- 15500586
TI  - Who is responsible for irresponsible drinking?

PMID- 15500587
TI  - More research on the alcohol industry's attempt to influence policy and science
      is needed.

PMID- 15500588
TI  - Industry influences: more case studies needed.

PMID- 15500589
TI  - Don't cover up distinct responsibilities, but co-operate on the action level
      under certain conditions.

PMID- 15500591
TI  - Adherence to pharmacotherapy in patients with alcohol and opioid dependence.
AB  - AIMS: An important factor that has thus far limited the effectiveness of
      pharmacotherapies for patients with alcohol and opioid dependence is poor
      adherence to medication regimens. This paper presents a review of issues related
      to medication adherence in patients with these substance use disorders. DESIGN
      AND METHODS: A literature review was conducted of English language publications
      relating to medication adherence among patients with alcohol or opioid
      dependence. FINDINGS: The paper places the topic in the context of adherence
      difficulties among patients with a variety of chronic medical and psychiatric
      illnesses. Difficulties measuring adherence are discussed, and strategies to
      improve medication adherence are reviewed. These include specific interventions
      that prescribing clinicians can implement in their individual meetings with
      patients; the use of external reinforcers, such as positive and negative
      contingencies, and involvement of family members or significant others; and
      specific prescribing and dosing practices that may improve adherence.
      CONCLUSIONS: As the use of pharmacotherapy for substance-dependent patients
      increases, rigorous and innovative approaches to encourage medication adherence
      should be sought.

PMID- 15500592
TI  - Risky drinking and alcohol use patterns in a national sample of women of
      childbearing age.
AB  - AIMS: We examined risky drinking and alcohol use patterns associated with
      prenatal effects of alcohol exposure in women of childbearing age, using various
      definitions of low-risk drinking. DESIGN: Computer-assisted telephone interview
      (CATI) methodology was used to gather information in a cross-sectional survey on
      alcohol use and problems, pregnancy and likelihood of future pregnancy. SETTING:
      Participants were respondents in the 2000 National Alcohol Survey (NAS, N10,
      response rate 58%) which includes men and women from all 50 states of the United
      States and the District of Columbia. PARTICIPANTS: A total of 1504 women aged 18
      39 years were included; 72 were pregnant, 511 were currently not pregnant but
      reported being likely to be pregnant in the next 5 years, and 921 women were
      neither pregnant nor likely to be in the next 5 years. MEASUREMENTS: Various
      alcohol use patterns in the past 12 months including average volume, amount per
      session, drinking with food and time spent drinking were assessed. FINDINGS:
      Seven per cent of childbearing age women exceeded guidelines used to classify
      women as risky drinkers in the past month. Thirty per cent were classified as
      risky drinkers when these guidelines were extended to past-year drinking.
      Examination of specific alcohol use patterns revealed that while under 10% of
      risky drinkers reported past-month heavy episodic drinking, 30% or more reported
      heavy episodic drinking and exceeding daily limits for alcohol consumption in the
      past year. CONCLUSIONS: Public health professionals should note that past-year
      drinking in a significant proportion of women of childbearing age exceeds
      guidelines for alcohol use. When targeting such prevention efforts, they should
      thus include assessment of past-year alcohol use patterns.

PMID- 15500593
TI  - Genetic and environmental contributions to age of onset of alcohol dependence
      symptoms in male twins.
AB  - AIMS: To investigate genetic and environmental influences on the development of
      specific alcohol dependence symptoms. DESIGN AND PARTICIPANTS: A classical twin
      study of 3372 male-male twin pairs in the Vietnam Era Twin (VET) Registry based
      on telephone interviews about alcohol use. MEASUREMENTS: The nine diagnostic
      symptoms according to the Diagnostic and Statistical Manual of Mental Disorder,
      version III (revised) (DSM-III-R) definition of alcohol dependence. Symptoms were
      grouped into those based on impaired control, biological effects and social
      consequences (Beresford's classification) or early versus late symptoms (Nelson's
      classification). Survival models with random effects were used to examine the age
      of onset of each symptom. FINDINGS: Approximately 38% of the variation in age of
      onset of each symptom group based on Beresford's classification is due to
      additive genetic factors. The age of onset of late symptoms from Nelson's
      classification appears to be most affected by genetic factors. Estimates of
      genetic effects for impaired control symptoms are greatly decreased when twins
      with comorbid psychiatric disorders are excluded. CONCLUSIONS: Our results
      support the heritability of age of onset of DSM-III-R-defined symptoms for
      alcohol dependence. However, no symptom group in Beresford's classification could
      be identified as more heritable than other symptom groups. A strong association
      between genetic vulnerability and co-occurring diseases for symptoms indicative
      of impaired control could be found. In addition, our findings show that the late
      symptom group could be a good candidate for subsequent genetic research.

PMID- 15500594
TI  - Web-based screening and brief intervention for hazardous drinking: a double-blind
      randomized controlled trial.
AB  - BACKGROUND: Strong evidence exists for the efficacy of screening and brief
      intervention for reducing hazardous drinking. However, problems have been
      highlighted with respect to its implementation in health-care systems, not least
      of which is a reluctance of some doctors to discuss alcohol proactively with
      their patients. AIMS: To determine the efficacy of a novel web-based screening
      and brief intervention (e-SBI) to reduce hazardous drinking. DESIGN: A double
      blind randomized controlled trial. SETTING: A university student health service.
      PARTICIPANTS: A total of 167 students (17-26 years) were recruited in the
      reception area and completed a 3-minute web-based screen including the Alcohol
      Use Disorder Identification Test (AUDIT) questionnaire. Of these, 112 tested
      positive, and 104 (52 females) who consented to follow-up were included in the
      trial. MEASUREMENTS: Drinking frequency, typical occasion quantity, total volume,
      heavy episode frequency (females > 80 g ethanol, males > 120 g ethanol), number
      of personal problems, an academic problems score. INTERVENTION: Participants were
      randomized to 10-15 minutes of web-based assessment and personalized feedback on
      their drinking (intervention, n = 51) or to a leaflet-only control group (n =
      53). FINDINGS: Mean baseline AUDIT scores for control and intervention groups
      were 16.6 (SD = 6.0) and 16.6 (SD = 5.7). At 6 weeks, participants receiving e
      SBI reported significantly lower total consumption (geometric mean ratio = 0.74;
      95% confidence interval: 0.56-0.96), lower heavy episode frequency (0.63; 0.42
      0.92) and fewer personal problems (0.70; 0.54-0.91). At 6 months personal
      problems remained lower (0.76; 0.60-0.97), although consumption did not differ
      significantly. At 6 months, academic problems were lower in the intervention
      group relative to controls (0.72; 0.51-1.02). CONCLUSIONS: e-SBI reduced
      hazardous drinking among university students, to an extent similar to that found
      for practitioner-delivered brief interventions in the general population. e-SBI
      offers promise as a strategy to reduce alcohol-related harm in a way that is non
      intrusive, appealing to the target group, and capable of being incorporated into
      primary care. Research is required to replicate the findings, to determine the
      duration of intervention effects, and to investigate the mechanisms by which the
      intervention operates.

PMID- 15500595
TI  - Times for healing: towards a typology of time-frames in Swiss alcohol and drug
      clinics.
AB  - AIM: To translate theoretical dimensions of 'social time' and 'clock time' in
      addiction treatment settings into empirical measures and to develop a typology of
      institutional time perspectives. METHOD: From November 2001 to February 2002, a
      mail survey was conducted with directors of 57 alcohol and drug clinics in the
      German-speaking part of Switzerland. Items measured the past and future
      orientation of the treatment programmes, elements of social time and clock time
      as part of organizational life and 'time bargaining' between therapists and
      clients. FINDINGS: Four clusters of temporal orientations emerged: 'clock time
      keepers' (who emphasize time control and future pessimism); 'nostalgic time
      riders' (focus on the 'good old days' but individualized planning); 'optimist
      speeders' (fast pacing, future control); and 'relaxed future optimists' (also
      future oriented but not sharing the idea of linear time). The time-frame also
      influences the negotiation of time in treatment between staff and patients:
      'relaxed future optimists' most frequently report diverging views, while
      'optimist speeders' seem to harmonize the views of patients and treatment staff
      more easily. Finally, the introduction of the harm reduction policy seems to
      covary with the ways in which time is viewed and used in treatment organizations.
      CONCLUSIONS: Treatment programmes differ in their view and use of time.
      Organizational times with varying dynamics, future-past orientations and time
      control interact with the organizational structure and socio-environmental
      factors. The capacity of programmes to adapt to changes in treatment policy and
      in the treatment system depends to some extent on organizational time
      orientation.

PMID- 15500596
TI  - The prevalence of injecting drug use in a Russian city: implications for harm
      reduction and coverage.
AB  - AIM: This study sought to estimate the prevalence of injecting drug users (IDU)
      in Togliatti city and to examine the implications of these estimates for HIV
      prevalence and harm reduction. DESIGN: Routine data sources of IDUs were
      identified. Covariate capture-recapture techniques were used on the individuals
      identified on the three data sources and used to estimate the number of IDU 'not
      observed' by the data sources, and thereby estimate the prevalence of IDU.
      SETTING: Togliatti City, Samara Oblast, Russian Federation. PARTICIPANTS: IDUs
      recorded on three data sources (narcology records, HIV positive test results and
      police arrest data) during 2001. MEASUREMENTS: Poisson regression models were
      fitted to the observed data, with interactions between data sources fitted to
      replicate 'dependencies' between those data sources. To select the best model the
      goodness of fit was approximated by chi2 distribution and the best-fitting model
      was selected on the basis of standard information criteria and log likelihood
      ratio tests. FINDINGS: The total estimated population of IDUs is 20 226 [95%
      confidence interval (CI): 16 971-24 749] giving a population prevalence of 5.4%
      (95% CI: 4.5-6.6%) of the registered population and 2.7% (95% CI: 2.4-3.5%) of
      the population (including migrants) aged 15-44 years. For every one IDU in
      contact with a service there were three out of contact. CONCLUSIONS: There is a
      high prevalence of IDU which, in the context of a fast-emerging IDU-associated
      HIV epidemic, will have serious public health implications.

PMID- 15500597
TI  - Evaluation of an injection depot formulation of buprenorphine: placebo
      comparison.
AB  - AIMS: Buprenorphine is a mu-opioid partial agonist that is marketed in a
      sublingual formulation as a treatment for opioid dependence. A microcapsule depot
      sustained-release formulation has been developed which may offer effective
      treatment of opioid dependence while also minimizing risks of illicit diversion
      or patient non-compliance. The present study examined the efficacy of depot
      buprenorphine in suppressing the opioid withdrawal syndrome and in attenuating
      the effects of exogenous opioid challenge. DESIGN: A placebo-controlled, double
      blind, randomized trial. SETTING: A closed residential research facility.
      PARTICIPANTS: A total of 15 opioid-dependent participants were enrolled into the
      6-week study. INTERVENTION: Fifteen participants were randomized to receive a
      single subcutaneous depot injection containing buprenorphine (58 mg) or placebo.
      Two participants, both of whom received placebo, terminated participation after
      depot administration. Thirteen participants (six buprenorphine, seven placebo)
      completed the 6-week study and were assessed throughout the study for signs and
      symptoms of opioid withdrawal and for response to weekly subcutaneous challenges
      with 3 mg hydromorphone. MEASUREMENT: Subjective, physiological and observer
      rated indices of opioid withdrawal and opioid agonist effects. FINDINGS: Depot
      buprenorphine provided more effective relief from opioid withdrawal than placebo,
      as evidenced by significantly fewer buprenorphine participants requiring
      supplemental medications for withdrawal suppression after depot administration
      compared to participants receiving placebo. In the weekly hydromorphone challenge
      sessions, depot buprenorphine significantly reduced opioid response on measures
      of subjective effects and pupillary diameter. CONCLUSIONS: Results from this
      double-blind, placebo-controlled study indicate that depot buprenorphine is
      effective in providing both withdrawal suppression and opioid blockade. Future
      studies examining additional doses and repeated dosing regimens with depot
      buprenorphine are warranted.

PMID- 15500598
TI  - Beyond the K-hole: a 3-year longitudinal investigation of the cognitive and
      subjective effects of ketamine in recreational users who have substantially
      reduced their use of the drug.
AB  - RATIONALE: Ketamine is a dissociative anaesthetic that is also a drug of abuse.
      Previous studies have demonstrated persisting episodic and semantic memory
      impairments in recreational ketamine users 3 days after taking ketamine. However,
      the degree to which these deficits might be reversible upon reduction or
      cessation of ketamine use was not known. OBJECTIVE: To follow-up a population of
      ketamine users tested 3 years previously and examine whether impairments observed
      3 days after drug use are enduring or reversible. METHODS: Eighteen ketamine
      users and 10 polydrug controls from studies conducted between 3 and 4 years
      earlier were re-tested on the same battery of cognitive tasks and subjective
      measures. These tapped episodic, semantic and working memory and executive and
      attentional functioning. Subjective schizotypal, dissociative, mood and bodily
      symptoms were also examined and a drug use history recorded. RESULTS: The
      ketamine users had reduced their frequency of use of ketamine by an average of
      88.3%. Performance of ketamine users on tasks tapping semantic memory had
      improved and this improvement was correlated with their reduction in ketamine
      use. On tasks tapping episodic memory and attentional functioning, ketamine users
      still showed deficits compared to polydrug controls. Higher levels of schizotypal
      symptoms and perceptual distortions were exhibited by the ketamine group,
      although dissociative symptoms were similar to controls. CONCLUSIONS: These
      findings indicate that semantic memory impairments associated with recreational
      ketamine are reversible upon marked reduction of use; however, impairments to
      episodic memory and possibly attentional functioning appear long-lasting. In
      addition, schizotypal symptoms and perceptual distortions may persist after
      cessation of ketamine use. Ketamine users, or potential users, should be aware of
      the enduring effects of this drug on aspects of memory and subjective experience.

PMID- 15500599
TI  - Are there gender differences in smoking cessation, with and without bupropion?
      Pooled- and meta-analyses of clinical trials of Bupropion SR.
AB  - AIMS: In this study, we examine gender differences in smoking cessation with and
      without treatment with Bupropion SR. We test whether women and men have
      comparable success rates quitting smoking regardless of treatment, whether
      Bupropion SR is effective for women, and whether Bupropion SR efficacy differs
      for men and women. DESIGN: A literature search was conducted to identify relevant
      trials. Data were analyzed with individual-level (pooled) and study-level (meta
      analytical) statistics. PARTICIPANTS: Data from 4421 participants in 12
      randomized smoking cessation trials of Bupropion SR 300 mg versus placebo were
      analyzed. FINDINGS: Results from the meta-analysis revealed that Bupropion SR was
      an effective aid to smoking cessation [odds ratio (OR) = 2.49, 95% confidence
      interval (CI) = 2.06-3.00]. Moreover, Bupropion SR proved to be an effective
      cessation aid for women (OR = 2.47, 95% CI = 1.92-3.17). No treatment-gender
      interaction was observed; women and men benefited equally from treatment with
      Bupropion SR (Q = 0.01, NS). Overall, women were less successful at quitting than
      men, regardless of treatment (OR = 0.79, 95% CI = 0.65-0.95). These results were
      replicated with pooled, individual-level analyses. CONCLUSIONS: Bupropion SR is
      an effective smoking cessation aid for women. In these trials, women have less
      success quitting smoking than men, whether treated with Bupropion SR or placebo.
      There is a need to understand more about why women are less able to quit.

PMID- 15500600
TI  - GP prescribing of nicotine replacement and bupropion to aid smoking cessation in
      England and Wales.
AB  - AIMS: Prescribing nicotine replacement therapy (NRT) or bupropion for smoking
      cessation is of considerable importance to public health but little is known
      about prescribing practices. This paper examines general practitioners' (GPs')
      prescribing patterns in Britain where these drugs are reimbursed. The results
      have implications for other health-care systems considering introducing
      reimbursement. DESIGN, PARTICIPANTS AND SETTING: Postal survey conducted in 2002
      of a random sample of 1088 GPs in England and Wales, of whom 642 (59%) responded.
      MEASURES: Number of requests GPs reported having received from patients for NRT
      and bupropion over the past month, the number of prescriptions they reported
      issuing and ratings of attitudes to these medications. FINDINGS: GPs reported
      receiving an average of 4.3 requests for NRT and 1.9 for bupropion in the
      previous month. They reported issuing 3.5 prescriptions for NRT and 1.2 for
      bupropion. Almost all GPs accepted that NRT (95%) and bupropion (97%) should be
      reimbursable on National Health Service (NHS) prescription. However, a
      significant minority of those who received requests for prescriptions did not
      issue any (8% for NRT and 26% for bupropion). This was related to whether they
      thought these products should be available on NHS prescription for both NRT and
      bupropion (OR = 0.66, P < 0.05), which in turn was related to beliefs about
      whether smokers should have to pay for treatment themselves, the cost
      effectiveness of NRT/bupropion and the low priority they would give NRT/bupropion
      in the drug budget. For bupropion, concern about side-effects independently
      predicted not prescribing [odds ratio (OR) = 1.46, P < 0.03]. CONCLUSION: In the
      British health-care system, which has a well-established system for technology
      assessment and professionally endorsed guidelines, a significant minority of GPs
      decline all patient requests for stop-smoking medicines.

PMID- 15500601
TI  - Depot formulations: will pharmacological advances improve treatment options and
      outcomes for substance abusers?

PMID- 15500602
TI  - Treatment of drug dependence enters a new high technological era.

PMID- 15500603
TI  - The opportunity for public health activism to reduce alcohol harm.

PMID- 15500615
TI  - A novel model of sensitization and oral tolerance to peanut protein.
AB  - The prevalence of food allergic diseases is rising and poses an increasing
      clinical problem. Peanut allergy affects around 1% of the population and is a
      common food allergy associated with severe clinical manifestations. The exact
      route of primary sensitization is unknown although the gastrointestinal immune
      system is likely to play an important role. Exposure of the gastrointestinal
      tract to soluble antigens normally leads to a state of antigen-specific systemic
      hyporesponsiveness (oral tolerance). A deviation from this process is thought to
      be responsible for food-allergic diseases. In this study, we have developed a
      murine model to investigate immunoregulatory processes after ingestion of peanut
      protein and compared this to a model of oral tolerance to chicken egg ovalbumin
      (OVA). We demonstrate that oral tolerance induction is highly dose dependent and
      differs for the allergenic proteins peanut and OVA. Tolerance to peanut requires
      a significantly higher oral dose than tolerance to OVA. Low doses of peanut are
      more likely to induce oral sensitization and increased production of interleukin
      4 and specific immunoglobulin E upon challenge. When tolerance is induced both T
      helper 1 and 2 responses are suppressed. These results show that oral tolerance
      to peanut can be induced experimentally but that peanut proteins have a potent
      sensitizing effect. This model can now be used to define regulatory mechanisms
      following oral exposure to allergenic proteins on local, mucosal and systemic
      immunity and to investigate the immunomodulating effects of non-oral routes of
      allergen exposure on the development of allergic sensitization to peanut and
      other food allergens.

PMID- 15500616
TI  - Interleukin-15 is not required for the induction or maintenance of orally induced
      peripheral tolerance.
AB  - Orally induced tolerance is a physiologically relevant form of peripheral
      tolerance, which is believed to be important for the prevention of pathological
      immune responses in the gut. Of several mechanisms proposed to mediate oral
      tolerance, one that has received much attention recently is the concept of
      regulatory CD4+ T cells. As recent studies have suggested that interleukin (IL)
      15 may be important for the differentiation and maintenance of regulatory CD4+ T
      cells, we have examined the role of IL-15 in oral tolerance, using a soluble form
      of the IL-15 receptor (sIL-15R) which blocks the biological effects of IL-15 in
      vivo. Oral tolerance induced by feeding mice ovalbumin (OVA) in a low-dose
      regimen believed to induce regulatory T cell activity was not affected by the
      administration of sIL-15R during either the induction or maintenance phase of
      tolerance. Thus, oral tolerance does not involve an IL-15-dependent mechanism.

PMID- 15500614
TI  - Interleukin-10 suppression of myeloid cell activation--a continuing puzzle.
AB  - Efforts to identify the signal transduction pathways used by interleukin-10 (IL
      10) have resulted in limited success. The anti-inflammatory effects elicited by
      IL-10, and the mechanisms by which these are mediated, are still relatively
      unknown. Understanding the signalling mechanisms behind the suppression of
      cytokine expression by IL-10 could be of potential therapeutic interest. Although
      the consensus is that the Janus kinase, Jak1, as well as the signal transducer
      and activator of transcription STAT3 are central, much controversy exists about
      the participation and roles of many other signalling pathways targeted by IL-10.
      The mechanisms of cytokine suppression proposed by various groups have included
      transcriptional, post-transcriptional and post-translational regulation of IL-10
      target genes; nevertheless no unifying model has emerged thus far. Here we would
      like to highlight novel findings and discuss their implications in the context of
      current understanding of IL-10 signalling.

PMID- 15500617
TI  - Ovine dendritic cells transduced with an adenoviral CTLA4eEGFP fusion protein
      construct induce hyporesponsiveness to allostimulation.
AB  - CTLA4 (CD152) is a transmembrane molecule expressed on activated T cells and
      functions as a negative regulator of T cell activation upon binding to the
      costimulatory molecules CD80/86. In this study, CTLA4eEGFP constructs were
      engineered by cloning the extracellular domains of ovine and human CTLA4 (CTLA4e)
      'in frame' with the enhanced green fluorescent protein (EGFP). Recombinant
      adenoviral vectors were generated by incorporation of the CTLA4eEGFP sequence
      into the adenoviral genome using homologous recombination in Esherichia coli. The
      functional activity of the adenoviral vectors was shown by the secretion of the
      CTLA4eEGFP upon infection of ovine fibroblasts and the binding of the fusion
      protein to the target ovine and human dendritic cells expressing CD80/86
      receptors by flow cytometry. The EGFP tag facilitated molecular size
      determinations and quantification of the secreted ovine CTLA4 fusion protein by
      immunoprecipitation and enzyme-linked immunosorbent assay (ELISA), respectively,
      using anti-GFP mAbs. Ovine dendritic cells obtained from pseudoafferent lymphatic
      cannulation of sheep were characterized based on high major histocompatibility
      complex (MHC) class II expression and cross-reactivity with monoclonal antibodies
      to the human dendritic cell markers, CD83 and CMRF-56. In addition, ovine
      dendritic cells (DC) were transfected with the adenoviral CTLA4eEGFP and when
      used as stimulators in a mixed lymphocyte reaction showed a reduced capacity to
      induce allogeneic lymphocyte proliferation. This study verifies that the ovine
      CTLA4eEGFP fusion protein functions similarly to its human homologue and that DC
      modified with adenoviral CTLA4-EGFP may provide an effective therapeutic approach
      in targeting alloreactive T cells to prolong allograft acceptance in a
      preclinical ovine model of renal transplantation.

PMID- 15500618
TI  - Dendritic cells and follicular dendritic cells express a novel ligand for CD38
      which influences their maturation and antibody responses.
AB  - CD38 is a cell surface molecule with ADP-ribosyl cyclase activity, which is
      predominantly expressed on lymphoid and myeloid cells. CD38 has a significant
      role in B-cell function as some anti-CD38 antibodies can deliver potent growth
      and differentiation signals, but the ligand that delivers this signal in mice is
      unknown. We used a chimeric protein of mouse CD38 and human immunogobulin G (IgG)
      (CD38-Ig) to identify a novel ligand for murine CD38 (CD38L) on networks of
      follicular dendritic cells (FDCs) as well as dendritic cells (DCs) in the spleen.
      Flow-cytometry found that all DC subsets expressed cytoplasmic CD38L but only
      fresh ex vivo CD11c+ CD11b- DCs had cell surface CD38L. Anti-CD38 antibody
      blocked the binding of CD38-Ig to CD38L, confirming the specificity of detection.
      CD38-Ig immuno-precipitated ligands of 66 and 130 kDa. Functional studies found
      that CD38-Ig along with anti-CD40 and anti-major histocompatibility complex (MHC)
      class II antibody provided maturation signals to DCs in vitro. When CD38-Ig was
      administered in vivo with antigen, IgG2a responses were significantly reduced,
      suggesting that B and T cells expressing CD38 may modulate the isotype of
      antibodies produced through interaction with CD38L on DCs. CD38-Ig also expanded
      FDC networks when administered in vivo. In conclusion, this study has identified
      a novel ligand for CD38 which has a role in functional interactions between
      lymphocytes and DCs or FDCs.

PMID- 15500619
TI  - Disparate ability of murine CD8alpha- and CD8alpha+ dendritic cell subsets to
      traverse endothelium is not determined by differential CD11b expression.
AB  - Upon Ag uptake and response to maturation stimuli, dendritic cells (DC) are
      directed through lymphatic or blood vessel endothelium to T cell areas of
      secondary lymphoid tissues by the constitutively expressed CC chemokines CCL19
      and CCL21. We have shown that mature (m) murine CD8alpha+ DC exhibit poorer
      migratory ability to these chemokines than classic CD8alpha- DC by quantifying
      their in vitro chemotaxis through unmodified Transwell filters. We hypothesized
      that lower surface expression (compared to CD8alpha- mDC) of the adhesion
      molecule CD11b on CD8alpha+ DC might limit their ability to adhere to filter
      pores in vitro and/or endothelium in vitro/in vivo. To test the role of this
      and/or other adhesion molecules (CD11a, CD31, CD54 and CD62L) in regulating
      murine DC subset migration, we used specific mAbs to block their function and
      quantified their migration through resting or tumour necrosis factor (TNF)-alpha
      activated endothelial cell (EC) layered-Transwell filters. Both CD8alpha+ and
      CD8alpha- subsets migrated through resting EC (albeit less than in the absence of
      EC) in response to CCL19 and CCL21, and migration through TNF-alpha-activated EC
      was enhanced. In contrast to reports concerning human DC, transendothelial
      migration of the murine DC subsets was not dependent on CD11b, CD31, or CD62L
      expression by these cells. CD54 and CD11a, however, were at least partly involved
      in DC/EC interactions. This is the first report to examine adhesion molecules
      involved in transendothelial migration of murine DC subsets.

PMID- 15500620
TI  - Heterogeneous expression of apolipoprotein-E by human macrophages.
AB  - Apolipoprotein-E (apoE) is expressed at high levels by macrophages. In addition
      to its role in lipid transport, macrophage-derived apoE plays an important role
      in immunoregulation. Previous studies have identified macrophage subpopulations
      that differ substantially in their ability to synthesize specific cytokines and
      enzymes, however, potential heterogeneous macrophage apoE expression has not been
      studied. Here we examined apoE expression in human THP-1 macrophages and monocyte
      derived macrophages (MDM). Using immunocytochemistry and flow cytometry methods
      we reveal a striking heterogeneity in macrophage apoE expression in both cell
      types. In phorbol-ester-differentiated THP-1 macrophages, 5% of the cells over
      expressed apoE at levels more than 50-fold higher than the rest of the
      population. ApoE over-expressing THP-1 macrophages contained condensed/fragmented
      nuclei and increased levels of activated caspase-3 indicating induction of
      apoptosis. In MDM, 3-5% of the cells also highly over-expressed apoE, up to 50
      fold higher than the rest of the population; however, this was not associated
      with obvious nuclear alterations. The apoE over-expressing MDM were larger, more
      granular, and more autofluorescent than the majority of cells and they contained
      numerous vesicle-like structures that appeared to be coated by apoE. Flow
      cytometry experiments indicated that the apoE over-expressing subpopulation of
      MDM were positive for CD14, CD11b/Mac-1 and CD68. These observations suggest that
      specific macrophage subpopulations may be important for apoE-mediated
      immunoregulation and clearly indicate that subpopulation heterogeneity should be
      taken into account when investigating macrophage apoE expression.

PMID- 15500621
TI  - Interleukin-10 secreted by B-1 cells modulates the phagocytic activity of murine
      macrophages in vitro.
AB  - As demonstrated previously in our laboratory, B-1 cells migrate from the
      peritoneal cavity of mice and home to a distant site of inflammation to become
      macrophage-like cells. However, the influence that these cells might have on the
      kinetics and fate of the inflammatory process is not known. Considering that
      macrophages are pivotal in the inflammatory reaction, we decided to investigate
      the possible influence B-1 cells could have on macrophage activities in vitro.
      Our results show that peritoneal macrophages from Xid mice, a mouse strain
      deprived of B-1 cells, have higher phagocytic indexes for zymozan particles when
      compared with macrophages from wild-type mice. Moreover, macrophages from wild
      type mice have a lower ability to release nitric oxide and hydrogen peroxide when
      compared with macrophages from Xid mice. Experiments using cocultures of B-1
      cells and macrophages from Xid mice in transwell plates demonstrated that B-1
      cells down-regulate macrophage activities. These observations also indicate that
      this phenomenon is not due to a physical interaction between these two cell
      populations. As B-1 cells are one of the main sources of interleukin (IL)-10, we
      demonstrate in this study that adherent peritoneal cells from Xid mice produce
      significantly less amounts of this cytokine in culture when compared with IL-10
      production by cells from wild-type mice. When B-1 cells from IL-10 knock-out mice
      and macrophages from wild-type mice were cocultured in transwell plates, the
      phagocytic index of macrophages was not altered demonstrating that B-1 cells can
      influence the effector functions of macrophages in vitro via IL-10 secretion.

PMID- 15500622
TI  - Analysis of the mechanisms involved in the stimulation of neutrophil apoptosis by
      tumour necrosis factor-alpha.
AB  - We have previously reported that human neutrophils pretreated with tumour
      necrosis factor-alpha (TNF-alpha) and then exposed to a variety of agents such as
      immune complexes, zymosan, phorbol 12-myristate 13-acetate (PMA), C5a, fMLP, or
      granulocyte-macrophage colony-stimulating factor (GM-CSF), undergo a dramatic
      stimulation of apoptosis, suggesting that TNF-alpha is able to prime an apoptotic
      death programme which can be rapidly triggered by different stimuli. We report
      here that this response involves the participation of Mac-1 (CD11b/CD18), is
      dependent on caspases 3, 8 and 9, and is associated with both a loss of
      mitochondrial transmembrane potential and a down-regulation in expression of the
      anti-apoptotic protein, Mcl-1. Interestingly, we also found that the anti
      apoptotic cytokine interleukin-1 (IL-1) improves the ability of TNF-alpha to
      promote apoptosis, supporting the notion than TNF-alpha, acting together with IL
      1, may favour the depletion of neutrophils from the inflammatory areas during the
      course of acute inflammation.

PMID- 15500623
TI  - CD27- CD4+ memory T cells define a differentiated memory population at both the
      functional and transcriptional levels.
AB  - The memory T-cell population is a heterogeneous population, including both
      effector cells, which exert a direct secondary immune response, and resting or
      intermediate cells, which serve as a reservoir and exert a possible regulatory
      role. To further dissect the T-cell memory population residing in the CD4+
      CD45RO+ T-cell pool, we studied the functional properties of memory populations
      identified by the CD27 marker. This marker clearly divides the memory population
      into two groups. One group consists of effector cells lacking CD27 and displaying
      a high antigen recall response. The other group consists of an intermediate
      memory population, displaying CD27. This latter group lacks an antigen recall
      response and requires costimulation for T-cell receptor triggering. To evaluate
      the function of the CD27+ memory pool, we analysed the transcriptional profile,
      using high-density microarray technology. These gene data strongly support the
      different functional profiles of CD27+ and CD27- memory populations, in terms of
      protein expression and the capacity to respond to antigen.

PMID- 15500624
TI  - Age-dependent variation in the proportion and number of intestinal lymphocyte
      subsets, especially natural killer T cells, double-positive CD4+ CD8+ cells and
      B220+ T cells, in mice.
AB  - The age-dependent variation in the proportion and number of lymphocyte subsets
      was examined at various extrathymic sites, including the liver, small intestine,
      colon and appendix in mice. In comparison with young mice (4 weeks of age), the
      number of total lymphocytes yielded by all tested organs was greater in adult (9
      weeks) and old (40 weeks) mice. The major lymphocyte subset that expanded with
      age was interleukin-2 receptor (IL-2R) beta+ CD3int cells (50% of them expressed
      NK1.1) in the liver, whereas it was CD3+ IL-2Rbeta- NK1.1- cells at all
      intraepithelial sites in the intestine. Although NK1.1+ CD3+ cells were present
      at intraepithelial sites in the intestine, the proportion of this subset was
      rather low. The ratio of CD4 to CD8 tended to decrease among natural killer T
      (NKT) cells and T cells at all intraepithelial sites in the intestine with age. A
      unique population of double-positive CD4+ CD8+ cells in the small intestine
      increased in old mice. B220+ T cells were found mainly in the appendix and colon,
      and the proportion of these T cells decreased in old mice. Conventional NKT cells
      were very few in Jalpha281-/- and CD1d-/- mice in the liver, while NKT cells
      which existed in the appendix remained unchanged even in these mice. This was
      because unconventional CD8+ NKT cells were present in the intestine. The present
      results suggest that despite the fact that both the liver and intraepithelial
      sites in the intestine carry many extrathymic T cells, the distribution of
      lymphocyte subsets and their age-associated variation are site-specific.

PMID- 15500625
TI  - Transcription of major histocompatibility complex class I (Kb) and transporter
      associated with antigen processing 1 and 2 genes is up-regulated with age.
AB  - The transporter associated with antigen processing 1 and 2 (TAP1 and TAP2) genes
      belong to the ATP-binding cassette family of transporter genes. They provide
      peptides necessary for the assembly of major histocompatibility complex (MHC)
      class I molecules by transporting these peptides into the endoplasmic reticulum.
      As MHC class I protein expression increases with age, we have explored the effect
      of age on the transcription of MHC class I genes (Kb) and TAP1 and TAP2 genes in
      C57BL/6 mice. Blood and spleen lymphocytes were isolated from mice aged from 3
      months to over 24 months. RNA was extracted and mRNA for Kb, TAP1, TAP2 was
      quantified using slot-blot hybridization followed by densitometry. There was a
      parallel age-related increase (1.5-fold) in blood lymphocyte mRNA of these genes
      from 3 months to 21 months. In mice over 24 months old there was a decrease in Kb
      and TAP1 mRNA, but an increase in TAP2 mRNA. In spleen lymphocytes an age-related
      increase in all three mRNA species occurred throughout life. While MHC class I
      and Tap genes underwent very similar age-related changes, MHC class I mRNA was
      about 50 times more abundant than either TAP1 or TAP2 mRNA.

PMID- 15500626
TI  - Pathogenesis of collagen-induced arthritis: modulation of disease by
      arthritogenic T-cell epitope location.
AB  - Collagen-induced arthritis (CIA) is an animal model of human rheumatoid arthritis
      that can be induced in susceptible mice by immunization with type II collagen
      (CII) or with collagen fragments, including cyanogen bromide (CB) peptides. One
      susceptible mouse strain, B10.RIII (I-Ar), has previously been found to respond
      to two major T-cell determinants, namely CII 610-618 (GPAGTAGAR) within CB10 and
      CII 445-453 (GPAGPAGER) within CB8. Although CB10 contains the immunodominant
      determinant, it is not arthritogenic. Using recombinant techniques, the
      determinant within CB10 was mutated to rCB10(T614P,A617E), generating a
      recombinant CB10 that in effect contained the arthritogenic epitope. When used
      for immunization, rCB10(T614P,A617E) was arthritogenic. This suggested that the
      arthritogenic property was intrinsic to the epitope and unrelated to its position
      within the CII molecule. To test this hypothesis, additional mutants were
      generated. The wild-type T-cell epitope of CB10 was deleted from its natural
      position, and the 'arthritogenic' GPAGPAGER T-cell epitope was inserted into the
      C-terminal portion of the CB10 peptide. The resulting peptide induced arthritis
      in B10.RIII mice. Adding a second copy of the T-cell determinant to other sites
      within CB10, however, had varying results. A second T-cell epitope located at the
      C-terminus of rCB10 significantly increased the incidence and severity of
      arthritis, while determinants placed in other positions had little effect. These
      data indicate that the T-cell epitope has intrinsic arthritogenic properties, but
      there are positional and structural constraints that affect its arthritogenicity.
      Enhanced arthritis was associated with an increased T-cell proliferation to the
      peptides, an increase in the level of inflammatory cytokines, and higher levels
      of anti-CII immunoglobulin. These data suggest that the position and copy number
      of T-cell determinants also affect the overall immune T-cell responses.

PMID- 15500628
TI  - Characterization of the B-cell inhibitory protein factor in Ixodes ricinus tick
      saliva: a potential role in enhanced Borrelia burgdoferi transmission.
AB  - We recently described the inhibition of host B lymphocytes by Ixodes ricinus tick
      saliva. In this study, we characterized the factor responsible for this activity
      and examined the modulation of lipopolysaccharide (LPS)- and Borrelia burgdorferi
      outer surface protein (Osp)-induced proliferation of naive murine B lymphocytes
      by an enriched fraction of this factor. The B-lymphocyte inhibitory activity was
      destroyed by trypsin treatment, indicating that a proteinaceous factor was
      responsible for this activity. The removal of glutathione-S-transferase (GST)
      from tick salivary glands extracts (SGE) showed that this B-cell inhibitory
      protein (BIP) was not a GST. Gel filtration liquid chromatography indicated that
      BIP has a native molecular weight of approximately 18,000. An enrichment
      protocol, using a combination of anion-exchange and reverse-phase liquid
      chromatography, was established. BIP-enriched fractions did not suppress T-cell
      proliferation. Delayed addition of BIP-enriched fractions, up to 7 hr after LPS
      addition, inhibited the proliferation of isolated B cells. BIP-enriched fractions
      dramatically inhibited both OspA- and OspC-induced proliferation of isolated B
      cells. These results strongly suggest that BIP may facilitate B. burgdorferi
      transmission by preventing B-cell activation, and also highlights the potential
      of BIP as a therapeutic agent in B-cell maladies.

PMID- 15500627
TI  - Immunosuppression, interleukin-10 synthesis and apoptosis are induced in rats
      inoculated with Cryptococcus neoformans glucuronoxylomannan.
AB  - Glucuronoxylomannan (GXM) is the major Cryptococcus neoformans capsular
      polysaccharide and represents the main virulence factor of this fungus. In in
      vitro studies we have demonstrated previously that this acidic and high-molecular
      weight polysaccharide suppresses lymphoproliferation, modulates cytokine
      production and promotes apoptosis in spleen mononuclear (Spm) cells from rats. In
      this study we demonstrate that these phenomena also occur in vivo after the
      intracardiac inoculation of GXM into normal Wistar rats. The results of this
      study show suppression of the proliferative response Spm cells to concanavalin A
      (Con A) or heat-killed C. neoformans (HKCn) in the first 2 weeks after
      polysaccharide administration. In addition, increased levels of interleukin (IL)
      10 were produced by Con A-stimulated Spm cells, coinciding with
      immunohistochemical GXM detection in the white pulp of spleen. In particular,
      high production of IL-10 with diminution of IL-2, interferon (IFN)-gamma and
      tumour necrosis factor (TNF)-alpha synthesis were detected 14 days after GXM
      administration. In situ cell death detection by TdT-mediated biotin-dUTP nick-end
      labelling (TUNEL) reaction in sections of spleen, lung and liver demonstrates
      apoptosis in tissues with deposits of GXM. These data demonstrate the in vivo
      ability of GXM to modify cytokine synthesis by Spm cells and to promote host cell
      apoptosis.

PMID- 15500630
TI  - Respiratory effects of experimental exposure to office dust.
AB  - The aim of this experiment was to test if healthy persons respond to exposures to
      normal office dust with objective or subjective effects in a dose-related way. If
      they did, the importance of their personal characteristics should be
      investigated. This paper presents the results related to respiratory effects
      caused by exposures to office dust. The experiment compared the responses of 24
      healthy non-sensitive adult subjects with no known hyperreactivity to exposure to
      normal office dust in the air at 136 and 390 microg/m3 with their responses in
      clean air. The exposure duration was 5.25 h in a climate chamber under controlled
      conditions. The dust had no major identifiable specific reactive compounds. There
      were no direct effects of dust exposures on nasal lavages or rhinometry. The
      overall indications of the experiment are that healthy subjects without any
      hypersensitive reactions seem to respond to exposure to house dust without
      specific reactive components. The only effect indicated was on eosinophil
      cationic protein in nasal lavages and peak flow. A delayed effect on peak
      expiratory flow was observed the day after the exposure. Other effects were seen
      but in opposite direction of expectations. Several deviations from the original
      design of the experiment prevent any definitive conclusions from being made from
      these findings before they have been confirmed in future experiments to come.
      PRACTICAL IMPLICATIONS: Reflecting the exploratory status of the study its major
      implication is to point at possible future hypotheses. The study implies that
      office dust may have an effect on occupants' lung function even at concentrations
      found in normal indoor environments. The influences of a multitude of response
      modifying variables were tested but no consistent pattern was found. The study
      does therefore not identify a specific risk group but suggests that among normal
      non-sensitized subjects most of the traditional risk factors can be rejected as
      single responsible risk factor.

PMID- 15500631
TI  - Evaluation of a high-volume portable bioaerosol sampler in laboratory and field
      environments.
AB  - This study investigated the physical and biological performances of a portable
      centrifugal sampler for viable bioaerosols, RCS High Flow. The performance of the
      test sampler in the laboratory and field environments was compared with that of a
      reference sampler, BioSampler. The laboratory experiments with non-biological
      particles of KCl, oleic acid, and polystyrene latex showed that the test
      sampler's collection efficiency is about 22% for 0.5-microm particles, 48% for
      1.0-microm particles, and approximately 100% for particles of 2.5 microm and
      larger. These tests indicated that the sampler's cut-off size (d50) was 1.1
      microm. The test sampler's physical performance when collecting the spores and
      vegetative cells of Bacillus subtilis var. niger (BG) was similar to that when
      collecting non-biological particles of the same size. In the laboratory tests,
      the RCS High Flow sampler was found to enumerate approximately 40% of BG spores
      and cells relative to the reference sampler, BioSampler. A similar ratio was
      found during testing in an indoor environment. This ratio decreased to below 10%
      when testing was performed in an outdoor environment. We hypothesize that the
      test sampler's underperformance compared with the BioSampler could be caused by
      the damage to sensitive microorganisms during the collection process, test
      sampler's sensitivity to wind direction and speed as well as break-up of particle
      aggregates during the impingement process in BioSampler, which resulted in more
      colony-forming units (CFUs) being counted by the reference sampler than by the
      test sampler. Overall, when the RCS High Plus is used to sample culturable
      airborne microorganisms, the results obtained may have to be adjusted to avoid
      potential underestimation of microorganism concentration in the air. PRACTICAL
      IMPLICATIONS: The laboratory testing of the RCS High Flow bioaerosol sampler
      showed that the sampler collects 1 microm particles and larger with an efficiency
      of 50% and higher; the efficiency reaches approximately 100% for particles of 2.5
      microm and larger. When considering this result, most of the airborne fungal
      spores would be collected with an efficiency between 50 and 100%. The field
      testing, however, indicated that the RCS High Flow sampler recovered from 41 to
      71% of microorganisms collected relative to the reference sampler, Biosampler,
      and this ratio dropped to below 5% during outdoor testing. Thus, while the RCS
      High Flow sampler offers certain advantages over other samplers for viable
      bioaerosols--it is lightweight, battery operated, and collects viable
      microorganisms at a high flow rate directly on agar media, the results obtained
      may have to be adjusted to avoid potential underestimation of microorganism
      concentration in the air, especially if sampling is performed outdoors.

PMID- 15500632
TI  - The influence of personality, measured by the Karolinska Scales of Personality
      (KSP), on symptoms among subjects in suspected sick buildings.
AB  - The aim was to study possible relationships between personality traits as
      measured by the Karolinska Scales of Personality (KSP), a self-report personality
      inventory based on psychobiological theory, and medical symptoms, in subjects
      with previous work history in suspected sick buildings. The study comprised 195
      participants from 19 consecutive cases of suspected sick buildings, initially
      collected in 1988-92. In 1998-89, the KSP inventory and a symptoms questionnaire
      were administered in a postal follow-up study. There were 16 questions on
      symptoms, including symptoms from the eyes, nose, throat, skin, and headache,
      tiredness, and a symptom score (SC), ranging from 0 to 16, was calculated. The
      questionnaire also requested information on personal factors, including age,
      gender, smoking habits, allergy and diagnosed asthma. The KSP ratings in the
      study group did not differ from the mean personality scale norm scores,
      calculated from an external reference group. Females had higher scores for
      somatic anxiety (P < 0.01), muscular tension (P < 0.001), psychic anxiety (P <
      0.01), psychasthenia (P < 0.05), indirect aggression (P < 0.05), and guilt (P <
      0.05), while males scored higher on detachment (P < 0.001). Subjects with higher
      SC were found to display higher degree of somatic anxiety (P < 0.001), muscular
      tension (P < 0.001), psychic anxiety (P < 0.001), psychasthenia (P < 0.001),
      inhibition of aggression (P < 0.05), detachment (P < 0.05), suspicion (P < 0.01),
      indirect aggression (P < 0.01), and verbal aggression (P < 0.05). In addition,
      ocular, respiratory, dermal, and systemic symptoms (headache and tiredness) were
      significantly related to anxiety- and aggressivity-related scales. There were
      associations between personality scales and change of symptom score (SC) during
      the 9-year period. The associations between KSP personality traits and symptoms
      were more pronounced in females. In conclusion, there are gender differences in
      personality and SBS symptoms. Personality may play a role in the occurrence of
      symptoms studied in indoor environmental epidemiology. Our results support a view
      that measurement of personality could be of value in future studies and
      vulnerability to environmental stress. PRACTICAL IMPLICATIONS: Personality and
      personal vulnerability should be considered in both indoor environmental
      epidemiology and practical handling of building with suspected indoor problem,
      especially when the technical investigations fail to identify any obvious
      technical malfunction. Moreover, personality aspects should be considered among
      subjects with possible vulnerable personality exposed to environmental stress,
      and personality diagnosis can be a complementary tool useful when assessing 'sick
      building patients' in the medical services. We found no evidence of severe
      personality pathology in among those working in workplaces with environmental
      problems so called 'sick buildings'.

PMID- 15500633
TI  - Assessment of the aerosolization potential for fungal spores in moldy homes.
AB  - The airborne fungal concentration measured with air samplers during specific time
      intervals may not adequately represent the indoor air quality because of the
      sporadic nature of spore release from sources. The conventional source evaluation
      (e.g. swab and tape sampling) characterizes the mold source but does not relate
      to the fraction of spores that can be aerosolized from a contaminated material.
      As an alternative to these methods, we have recently developed and laboratory
      tested a novel Fungal Spore Source Strength Tester (FSSST). It allows assessing
      the potential of aerosolization of fungal spores from contaminated surfaces under
      the most favorable release conditions. In this study, the FSSST was used to
      characterize the release of spores from four building materials in mold-problem
      homes. The spores of different species were efficiently aerosolized by the FSSST,
      exhibiting a total spore release rate ranging approximately from 10(2) to 10(3)
      cm2/min. For all tested materials, <2% of the spores on the contaminated surface
      were released during the tests. The airborne spore concentration estimated from
      the release rate data was found in most cases to be significantly greater than
      the concentration actually measured in these environments with simultaneous air
      sampling. The results suggest that the FSSST can be used for the assessment of
      maximum potential exposure to airborne spores released from identified sources in
      homes. PRACTICAL IMPLICATIONS: A recently developed FSSST was found to be
      suitable to measure the aerosolization potential of indoor fungal sources at the
      most favorable release conditions. The FSSST generates the data that allows
      assessing the strength of mold sources in homes with respect to their maximum
      ability to contaminate indoor air with fungi. The novel approach bridges two
      conventional methods, the air sampling and the direct source evaluation (e.g.
      swab sampling), thus providing a better representation of the airborne fungal
      exposure than these methods individually. The device prototype can be used for
      evaluating the effectiveness of environmental interventions by taking samples
      before and after the intervention. As a broader application, the FSSST can be
      utilized for assessing the release of various hazardous biological and non
      biological particles from contaminated surfaces.

PMID- 15500634
TI  - Exposure to the mixtures of organic compounds in homes in Japan.
AB  - The aim of the study reported herein was to characterize occupants' simultaneous
      exposure to mixtures of organic compounds in homes. Statistical distributions for
      concentrations of 28 organic compounds (17 VOCs and 11 aldehydes) measured in
      1417 homes were generated to analyze concentration distributions. Three candidate
      distributions were identified for fitting the measured data: log-normal,
      exponential and gamma distributions. It appears from the results of fitting tests
      that gamma distributions are capable of representing 28 compound concentrations.
      Probability distributions show that formaldehyde and acetaldehyde ranged from 25
      to 220 microg/m3 at 90% probabilities and most VOCs ranged from 3 to 80 microg/m3
      at 90% probabilities. In order to characterize the occupant's exposure to the
      mixtures, the joint probability distributions of organic compounds were generated
      from the best-fitted distributions of individual compounds under the assumption
      that concentrations of organic compounds are mutually independent in homes. These
      joint distributions provided the statistical data for characterizing the
      occupant's exposure to the mixtures of organic compounds in homes. PRACTICAL
      IMPLICATIONS: Occupants often encounter not just one compound in indoor
      environments, but many compounds due to their concurrent emissions from several
      sources. This paper describes characteristics of statistical distributions for
      concentrations of 17 VOCs and 11 aldehydes in homes in Japan. After applying a
      probability model to the occupants' simultaneous exposure to mixtures of organic
      compounds, the authors interpret the current state of the occupant's exposure to
      the mixtures within homes using joint probability distributions of 28 organic
      compounds.

PMID- 15500635
TI  - Tobacco smoking increases dramatically air concentrations of endotoxin.
AB  - We used a mass spectrometry-based assay for identifying the endotoxin
      (lipopolysaccharide, LPS) marker (R)-3-hydroxytetradecanoic acid in cigarette
      smoke particles and found that smoking involved inhalation of 17.4 pmol of
      endotoxin per each smoked cigarette. Indoor exposure to environmental tobacco
      smoke (ETS) entailed inhalation of 12.1 pmol of LPS/m3 air, an amount that was
      120 times higher than the levels found in smoke-free indoor air. Endotoxin is one
      of the most potent inflammatory agents known, hence our results may help to
      explain the high prevalence of respiratory disorders among smokers, and they may
      also draw attention to a hitherto unknown or neglected risk factor of ETS.
      PRACTICAL IMPLICATIONS: Endotoxin represents a largely neglected risk factor of
      smoking and passive smoking and this knowledge may lead to a reduced smoking.

PMID- 15500636
TI  - Building-related respiratory symptoms can be predicted with semi-quantitative
      indices of exposure to dampness and mold.
AB  - Using a semi-quantitative mold exposure index, the National Institute for
      Occupational Safety and Health (NIOSH) investigated 13 college buildings to
      examine whether building-related respiratory symptoms among employees are
      associated with environmental exposure to mold and dampness in buildings. We
      collected data on upper and lower respiratory symptoms and their building
      relatedness, and time spent in specific rooms with a self-administered
      questionnaires. Trained NIOSH industrial hygienists classified rooms for water
      stains, visible mold, mold odor, and moisture using semi-quantitative scales and
      then estimated individual exposure indices weighted by the time spent in specific
      rooms. The semi-quantitative exposure indices significantly predicted building
      related respiratory symptoms, including wheeze [odds ratio (OR) = 2.3; 95%
      confidence interval (CI) = 1.1-4.5], chest tightness (OR = 2.2; 95% CI = 1.1
      4.6), shortness of breath (OR = 2.7; 95% CI = 1.2-6.1), nasal (OR = 2.5; 95% CI =
      1.3-4.7) and sinus (OR = 2.2; 95% CI = 1.2-4.1) symptoms, with exposure-response
      relationships. We found that conditions suggestive of indoor mold exposure at
      work were associated with building-related respiratory symptoms. Our findings
      suggest that observational semi-quantitative indices of exposure to dampness and
      mold can support action to prevent building-related respiratory diseases.
      PRACTICAL IMPLICATIONS: Current air sampling methods have major limitations in
      assessing exposure to mold and other biological agents that may prevent the
      demonstration of associations of bioaerosol exposure with health. Our study
      demonstrates that semi-quantitative dampness/mold exposure indices, based solely
      on visual and olfactory observation and weighted by time spent in specific rooms,
      can predict existence of excessive building-related respiratory symptoms and
      diseases. Relative extent of water stains, visible mold, mold odor, or moisture
      can be used to prioritize remediation to reduce potential risk of building
      related respiratory diseases. From a public health perspective, these
      observational findings justify action to correct water leaks and repair water
      damage in order to prevent building-related respiratory diseases. This approach
      can also be a basis for developing practical building-diagnostic tools for water
      incursion.

PMID- 15500637
TI  - Effects of furniture polish on release of cat allergen-laden dust from wood
      surfaces.
AB  - The purpose of this study was to evaluate the effects of furniture polish (FP) on
      the release of cat allergen (Fel d 1)-laden dust from wood surfaces and decay of
      Fel d 1 in dust over time. About 2 g of sieved (150 microm screen) allergen-laden
      dust was introduced as an aerosol into an experimental chamber by a Pitt-3
      generator and allowed to settle onto two finished wood surfaces pre-treated with
      either distilled water (DW) or FP. After 24 h, each surface was vacuumed into
      separate plastic cassettes loaded with 37 mm diameter, 0.4 microm pore,
      polycarbonate filters. The recovered dust was weighed, extracted in phosphate
      buffered saline, and assayed for Fel d 1 content using a two-site monoclonal
      antibody ELISA. After vacuuming, the remaining dust on the wood surfaces was
      wiped up with a water-moistened swab. The dusts were extracted from the swabs and
      assayed by ELISA for Fel d 1. More Fel d 1 was recovered by vacuuming from DW-pre
      treated surfaces than from FP pre-treated surfaces (100% vs. 69 +/- 66%). On the
      contrary, more residual Fel d 1 (>99.9%) on the vacuumed surfaces was recovered
      from FP than from DW pre-treated surfaces by wet swabs. The concentration of Fel
      d 1 in dust did not change significantly at room temperature over 80 days. In
      conclusion, FP on wood surfaces makes dust stick to the surface, which likely
      reduces the release of allergen-laden dust from the wood surface. PRACTICAL
      IMPLICATIONS: Re-aerosolization of cat allergen-laden dusts from wood surfaces
      (e.g. wood floor or furniture) significantly increases the concentration of
      airborne cat allergens. Our study indicates that exposure to airborne cat
      allergens might be reduced by surface treatment with commercially available FP
      because cat allergen-laden dusts stuck more tightly to the wood surface treated
      with FP.

PMID- 15500638
TI  - Nicotine effects on skin: are they positive or negative?
AB  - The adverse effects of tobacco on the skin are well known but the role of
      nicotine is more controversial. Nicotinic receptors are expressed in the skin, on
      keratinocytes, fibroblasts and blood vessels. Nicotine induces vasoconstriction
      associated with local hyperaemia. It inhibits inflammation through effects on
      central and peripheral nervous system and through direct effect on immune cells.
      It delays wound healing and accelerates skin aging. The role of nicotine on skin
      diseases remains unclear. Therapeutic effects of nicotine could be possible and
      this a new stimulating field of research.

PMID- 15500639
TI  - Anti-vascular endothelial growth factor receptor-2 (Flk-1/KDR) antibody
      suppresses contact hypersensitivity.
AB  - The angiogenic mediator vascular endothelial growth factor (VEGF) and its
      receptors (VEGFRs) have been studied extensively in neoplastic disease and some
      inflammatory conditions. Contact hypersensitivity (CHS) is a prototypic
      Langerhans' cell-dependent, T-helper (Th) 1 cell-mediated inflammatory skin
      disease that is now also thought to involve angiogenic mediators. The purpose of
      our study was to examine the role of angiogenesis and VEGF in CHS. We
      demonstrated that VEGF production is up-regulated in murine skin after challenge
      with dinitrofluorobenzene. Administration of a monoclonal antibody directed
      against the VEGFR-2 (DC101) resulted in a 28.8% decrease in CHS response (P <
      0.001). Examination of the DC101-treated mouse skin 24 h after challenge revealed
      decreases in dermal inflammatory cellular infiltrates and total vessel area.
      Furthermore, mRNA and protein of the Th1-type cytokine interferon (IFN)-gamma was
      significantly down-regulated in skin of DC101-treated animals 24 h after
      challenge. The results of the study demonstrate that VEGFR-2 blockade
      significantly reduces vascular enlargement and edema formation and effects IFN
      gamma expression in the skin during challenge in CHS. Our findings suggest that
      DC101 could function by reducing inflammatory cell migration and hence IFN-gamma
      expression during the CHS response.

PMID- 15500640
TI  - Local rh-VEGF administration enhances skin flap survival more than other types of
      rh-VEGF administration: a clinical, morphological and immunohistochemical study.
AB  - The aim of the present study was to evaluate experimentally whether
      administration of recombinant (rh) vascular endothelial growth factor (VEGF) can
      protect skin flaps from necrosis and to study the optimum mode of rh-VEGF
      administration. We used rats to study the effects of local or systemic
      administration of rh-VEGF on skin flap during surgery; we also tested
      preoperative systemic administration of rh-VEGF to assess whether it may prepare
      the tissue to respond to the hypoxic injury better than previously tested
      methods. The animals were 30 male Sprague-Dawley rats. Group I rats received
      multiple systemic injections of rh-VEGF in the tail artery prior to flap
      dissection. Group II rats were injected with rh-VEGF in the clamped left
      epigastric artery during flap dissection; in this group, the left flaps thus
      received rh-VEGF locally (via incubation for 10 min during hypoxia) and the right
      flaps systemically, after blood flow restoration. Group III received saline
      solution instead of VEGF in the same way as group II. Skin samples from the
      distal portion of the flaps were collected on day 7 for morphological and
      immunohistochemical analysis. The flaps exhibiting the least necrosis were those
      treated with local rh-VEGF, followed by those treated with systemic rh-VEGF. The
      flaps that received rh-VEGF locally showed a strong VEGF expression on
      keratinocytes and endothelial cells, the greatest amount of mature and newly
      formed vessels and strong survivin expression in endothelial cells. Local rh-VEGF
      administration should thus be considered as an effective therapeutic option to
      enhance the survival of a tissue at risk for perfusion.

PMID- 15500641
TI  - Extracellular superoxide dismutase tissue distribution and the patterns of
      superoxide dismutase mRNA expression following ultraviolet irradiation on mouse
      skin.
AB  - Superoxide dismutases (SODs) are believed to play a crucial role in protecting
      cells against oxygen toxicity. There are three forms of SOD: cytosolic Cu-Zn SOD,
      mitochondrial Mn SOD, and extracellular SOD (EC SOD). Extracellular SOD is
      primarily a tissue enzyme, but the role of EC SOD in skin is unclear. Therefore,
      this study investigated the distribution of EC SOD in the skin using
      immunohistochemistry and examining the patterns of EC SOD gene expression
      following ultraviolet (UV) irradiation in comparison with those of Cu-Zn SOD and
      Mn SOD in mouse dorsal skin using Northern blot analysis. Immunohistochemical
      analysis showed that EC SOD was abundantly located in the epidermis as well as in
      the dermis, but the gene expression of EC SOD mRNA was more abundant in the
      dermis than in the epidermis. The gene expression levels of all three types of
      SODs after UV irradiation were induced differently according to the type and UV
      irradiation dose. The EC SOD mRNA expression level was increased relatively later
      than that of Cu-Zn SOD and Mn SOD. The EC SOD mRNA level was significantly higher
      at 6 h and 48 h after UVA irradiation and psoralen plus ultraviolet-A treatment,
      respectively. Ultraviolet-B irradiation increased the EC SOD mRNA expression
      level, with maximum at 48 h. These suggest that EC SOD participates in the
      majority of antioxidant systems in the skin, and it may have different defensive
      roles from Cu-Zn SOD and Mn SOD against UV-induced injury of the skin.

PMID- 15500642
TI  - Plakin proteins are coordinately cleaved during apoptosis but preferentially
      through the action of different caspases.
AB  - In epithelial cells, cell-cell and cell-matrix junctions, desmosomes and
      hemidesmosomes, provide anchorage sites for the keratin-intermediate filaments.
      The plakin proteins desmoplakin (DP), plectin, and periplakin represent
      intracellular constituents of these adhesion junctions. In staurosporine-treated
      apoptotic HaCaT cells, DP, plectin, and periplakin became cleaved coordinately
      with the elimination of keratins 10 and 14, while involucrin, actin, and keratin
      18 displayed considerable stability. The caspase inhibitor zVAD-fmk prevented
      both the cell detachment and protein cleavage, indicating the function of
      caspases in these events. Closer examination in vitro revealed that while
      caspases 2 and 4 most efficiently cleaved DP, and plectin served as a target for
      caspases 3 and 7, periplakin as well as keratins were cleaved by caspase 6. The
      involvement of multiple caspases in the destruction of epithelial cell integrity
      ensures the efficient elimination of cytoskeleton, but also provides specificity
      for selectively targeting individual adhesion molecules.

PMID- 15500643
TI  - High plasminogen activator inhibitor type 2 expression is a hallmark of
      scleroderma fibroblasts in vitro.
AB  - Systemic scleroderma is a chronic disease, which leads to fibrosis of the skin
      and internal organs. Fibroblasts obtained from patients with this disease
      demonstrate an activated state in culture. We, in this study, report strong,
      constitutive overexpression of plasminogen activator inhibitor type-2 (PAI-2) in
      scleroderma fibroblasts and demonstrate that this induction observed at the mRNA
      and protein level is dependent on serum addition. Induced PAI-2 protein levels
      were restricted to the non-glycosylated 47-kDa form, which is located
      intracellularly. Induction was stable for at least 12 passages. No modulation by
      fibrogenic cytokines--for example, transforming growth factor-beta1 or connective
      tissue growth factor--or by antagonizing IL-1 receptors was observed. The data
      indicate that scleroderma fibroblasts are more sensitive to the induction of PAI
      2 expression than control fibroblasts by a presently unknown factor in serum.

PMID- 15500644
TI  - The -431C>T polymorphism of thymus and activation-regulated chemokine increases
      the promoter activity but is not associated with susceptibility to atopic
      dermatitis in Japanese patients.
AB  - BACKGROUND: Thymus and activation-regulated chemokine (TARC) plays an important
      role in the pathogenesis of atopic dermatitis (AD). We recently detected the
      single nucleotide polymorphism (SNP) (-431C>T) in the 5'-flanking region of TARC
      gene. OBJECTIVES: To examine whether the -431C>T SNP of the TARC gene is
      associated with susceptibility to AD and whether it affects the promoter activity
      of the TARC gene. METHODS: We investigated the genotype and allele frequencies of
      the SNP in 193 AD patients and 158 healthy controls by polymerase chain reaction
      restriction fragment length polymorphism method. We compared the promoter
      activities between TARC promoter carrying 431C and that carrying -431T by
      transient-transfection assay in DJM-1 cell line. RESULTS: There were no
      significant differences in genotype or allele frequencies between AD patients and
      controls (genotype: P = 0.38, allele: P = 0.22). Luciferase activity was higher
      in -431T constructs than in -431C constructs (2.3-fold, P = 9.5 x 10(-6)).
      CONCLUSION: These results suggest that the -431C>T SNP of the TARC gene enhances
      the promoter activity of TARC gene but is not associated with susceptibility to
      AD in Japanese population.

PMID- 15500647
TI  - Dermal dendritic melanocytic proliferations: an update.
AB  - Dermal dendritic melanocytic proliferations are a broad group of congenital and
      acquired melanocytic lesions characterized by the presence of dermal spindled and
      dendritic cells resembling melanocytes migrating from the neural crest to the
      epidermis. Historically, they were subdivided into dermal melanocytoses (naevus
      of Ota, Ito, Mongolian spot and related conditions), blue naevi and malignant
      blue naevi. The purpose of this review is to provide an update on recent
      developments in the field with emphasis on new entities and their differential
      diagnosis.

PMID- 15500648
TI  - The diagnostic utility of MOC31, BerEP4, RCC marker and CD10 in the
      classification of renal cell carcinoma and renal oncocytoma: an
      immunohistochemical analysis of 328 cases.
AB  - AIMS: To demonstrate the diagnostic utility of MOC31, BerEP4, renal cell
      carcinoma marker (RCC Ma) and CD10 in the classification of RCC and renal
      oncocytoma, based upon a comprehensive immunohistochemical analysis. METHODS AND
      RESULTS: Immunohistochemistry was performed on 328 samples consisting of 256
      clear cell/conventional, 27 papillary, 28 chromophobe, five collecting duct, five
      unclassified RCCs and seven renal oncocytomas using antibodies MOC31, BerEP4 and
      antibodies against cytokeratins (KL-1, CAM5.2, 34betaE12, cytokeratin 7), RCC Ma,
      epithelial membrane antigen, E-cadherin, CD10, CD15 and vimentin. Multivariate
      analysis showed that MOC31, BerEP4, RCC Ma and CD10 have discriminatory value.
      MOC31 and BerEP4 chiefly labelled distal tubules of normal kidney while RCC Ma
      and CD10 labelled the proximal tubules. Twenty-three chromophobe RCCs (82%) were
      reactive for MOC31, while only four clear cell RCCs and three papillary RCCs were
      positive for this marker. Clear cell RCCs were characterized by a high positive
      rate for CD10 (82%) and a low positive rate for BerEP4 (27%). Papillary RCCs
      frequently coexpressed RCC Ma and BerEP4 (51%). All renal oncocytomas were
      negative for MOC31 and CD10. CONCLUSIONS: MOC31 has diagnostic merit in
      discerning chromophobe RCC. The CD10+/BerEP4- profile and RCC Ma+/BerEP4+ profile
      achieve moderate sensitivity and good specificity for clear cell RCC and
      papillary RCC, respectively. The non-reactivity for both MOC31 and CD10 is
      helpful in distinguishing renal oncocytoma from RCC. When properly selected,
      antibodies have immunohistochemical diagnostic utility for the classification of
      renal cortical epithelial tumours.

PMID- 15500649
TI  - CD10 is a diagnostic and prognostic marker in renal malignancies.
AB  - AIMS: To determine the diagnostic and prognostic value of CD10 immunoreactivity
      in renal cell carcinomas (RCCs) and transitional cell carcinomas (TCCs). METHODS
      AND RESULTS: CD10 expression was investigated in primary (n = 180) and metastatic
      (n = 58) RCCs and upper urinary tract TCCs (n = 53) using a tissue microarray
      technique. One hundred and fifty-four of 172 (90%) evaluable primary and 48/56
      (86%) evaluable metastatic RCCs expressed CD10. Extensive immunoreactivity
      (positivity of >50% cancer cells) decreased with rising tumour grade in
      conventional RCCs [G1/G2 72/81 (89%), G3/G4 33/48 (69%); P = 0.009]. Chromophobe
      RCCs showed a significantly lower overall and extensive immunoreactivity compared
      with conventional tumours (P < 0.001). In papillary RCCs immunoreactivity of more
      than 10% of cancer cells for CD10 was seen more often in type 2 (7/8, 88%)
      compared with type 1 (5/12, 42%; P =0.054) tumours. In conventional RCCs, pure
      apical membranous staining was associated with low tumour stage (P = 0.003), low
      grade (P = 0.004) and improved prognosis on univariate analysis (P = 0.031). TCCs
      were less frequently stained (51%). Extensive staining, however, was associated
      with high-stage tumours (P = 0.024), high-grade (P = 0.073) tumours, and was
      associated with shorter disease-free survival in univariate analysis (P = 0.003).
      CONCLUSIONS: CD10 proved to be an additional marker for renal malignancies with
      predominantly diagnostic potential.

PMID- 15500650
TI  - Prognostic analysis of pulmonary adenocarcinoma subclassification with special
      consideration of papillary and bronchioloalveolar types.
AB  - AIMS: The third edition of the World Health Organization (WHO) classification of
      lung tumours has been published and is expected to become the standard
      nomenclature. The aim of this study was to assess the usability and prognostic
      significance of the WHO classification in comparison with other recent
      classifications. METHODS AND RESULTS: One hundred and forty-seven resected
      pulmonary adenocarcinoma cases were reviewed and histologically classified
      according to the WHO classification (1999) and the classification by Noguchi
      (1995). Papillary carcinomas as described by Silver and Askin (1997) were also
      identified. Since the papillary type in the WHO classification is not strictly
      defined, we compared the following two kinds of WHO classification: (i) WHO-N;
      WHO classification adopting Noguchi Type F as the definition of the papillary
      type, namely, pure papillary adenocarcinoma without a bronchioloalveolar
      component; (ii) WHO-SA; WHO classification adopting papillary carcinoma by Silver
      and Askin as the definition of the papillary type, namely, tumour with papillary
      structure constituting at least 75% of the lesion. The bronchioloalveolar
      carcinoma of the WHO classification showed a better prognosis than other subtypes
      in both overall and Stage I disease limited survival analysis. In analysis
      limited to Stage III disease, only the papillary type of WHO-SA showed a
      significantly worse prognosis. CONCLUSIONS: WHO-SA is recommended for prognostic
      correlation.

PMID- 15500651
TI  - Mucin expression in peripheral airways of patients with chronic obstructive
      pulmonary disease.
AB  - AIMS: To study the expression of mucins in peripheral airways in patients with
      chronic obstructive pulmonary disease (COPD). METHODS AND RESULTS: Peripheral
      lung sections from smokers with COPD (n = 9) and age-matched controls including
      smokers (n = 11) and lifelong non-smokers with normal lung function (n = 6) were
      stained with alcian blue, periodic acid-Schiff (PAS) and by immunohistochemistry
      of mucins (MUC): MUC2, MUC4, MUC5AC, MUC5B and MUC6. Histochemical staining and
      immunoreactivity of bronchiolar epithelium were graded and the presence or
      absence of stained mucus in the bronchiolar lumen was evaluated. There were no
      differences in alcian blue and PAS epithelial staining between the three groups.
      Intraluminal PAS staining was significantly more frequent among COPD subjects (P
      < 0.05). The expression of MUC5AC was significantly higher in the bronchiolar
      epithelium of patients with COPD (P < 0.05). Within the bronchiolar lumen, the
      predominant mucin was MUC5B. Intraluminal MUC5B was significantly more frequent
      among COPD patients (P < 0.05). CONCLUSIONS: COPD is specifically associated with
      increased expression of MUC5B in the bronchiolar lumen and of the mucin MUC5AC in
      the bronchiolar epithelium. These changes in mucin production in the peripheral
      airways may contribute to the pathophysiology of COPD.

PMID- 15500652
TI  - Gastric medullary carcinoma, a distinct entity associated with microsatellite
      instability-H, prominent intraepithelial lymphocytes and improved prognosis.
AB  - AIMS: To determine the clinicopathological and molecular features of gastric
      medullary cancer. METHODS AND RESULTS: Clinicopathological review and
      microsatellite instability (MSI) analysis were carried out on 17 gastric
      medullary and 64 non-medullary cancers. In addition to characteristic
      histopathology, gastric medullary cancers had certain prominent features: (i) the
      average survival time was longer in medullary and low-grade non-medullary cancers
      than in high-grade (P = 0.004); (ii) serosal involvement was less common in
      medullary cancers (29.4%, 5/17) than in non-medullary cancers (9.4%, 6/64) (P <
      0.05) while pushing borders were more common in medullary cancers (70.6%, 12/17
      versus 17.2%, 11/64, P = 0); (iii) the presence of intraepithelial lymphocytes
      (IELs) in medullary and non-medullary cancers was 2380/10 high-power field (HPF)
      and 147/10 HPF (P = 0), respectively. Both peritumoural infiltrating lymphocytes
      (pTIL) and a Crohn's-like reaction were more common in medullary cancers than in
      non-medullary (pTIL 35.3%, 6/17 versus 3.1%, 2/64; a Crohn's-like reaction 70.6%,
      12/17 versus 32.8%, 21/64; P < 0.05); (iv) medullary and high-grade non-medullary
      cancers were more associated with reduced ECD expression in comparison with low
      grade cancers (P < 0.05); (v) higher MSI-H (Bat26+) rate was observed in
      medullary cancers (41.2%, 7/17) than in non-medullary (1.6%, 1/64) (P = 0).
      CONCLUSIONS: Gastric medullary cancer has distinct clinicopathological features
      and genetic alterations. Two subtypes of gastric medullary cancers, Bat26+ and
      Bat26-, might have prognostic implications, thus analysis of Bat26 may be of
      clinical value.

PMID- 15500653
TI  - Galectin-3 does not reliably distinguish benign from malignant thyroid neoplasms.
AB  - AIMS: To determine whether galectin-3 is a sensitive indicator of thyroid
      malignancy. It has been suggested as a potential marker for differentiating
      thyroid carcinoma from benign or non-neoplastic lesions in preoperative fine
      needle aspirates (FNAs). METHODS: Galectin-3 protein expression was assessed by
      immunohistochemistry in formalin-fixed thyroid tissues from 124 patients with
      histological diagnoses of papillary carcinoma (n = 38), follicular carcinoma (n =
      19), follicular adenoma (n = 32) and dominant nodules of multinodular goitre (n =
      35). Expression of galectin-3 was also assessed by Western blotting in 24 fresh
      thyroid tissues. RESULTS: Galectin-3 expression was observed in the majority of
      carcinomas (papillary 92%; follicular 74%). However, a large proportion of
      follicular adenomas (72%) and multinodular goitres (57%) also expressed galectin
      3. In addition, galectin-3 expression was observed in epithelial cells of normal
      thyroid tissue and Hashimoto's thyroiditis. Galectin-3 immunopositivity was
      significantly greater in papillary carcinomas than in dominant nodules or
      follicular adenomas (P < 0.0001, P = 0.0005, respectively). However, galectin-3
      expression was no greater in follicular carcinomas than in follicular adenomas (P
      = 0.8735). Western blotting analysis confirmed both the specificity of the
      antiserum and expression of galectin-3 in multinodular goitres, follicular
      adenomas/carcinomas and papillary carcinomas. CONCLUSION: The data demonstrate
      that galectin-3 is not a reliable immunohistochemical marker to distinguish
      benign from malignant thyroid follicular lesions.

PMID- 15500654
TI  - The pattern and frequency of t(14;18) translocation and immunophenotype in Asian
      follicular lymphoma.
AB  - AIMS: Follicular lymphoma is frequently associated with t(14;18)(q32;q21)
      translocation. This study was undertaken to determine the pattern of Bcl-2, CD10
      and Bcl-6 expression in relation to t(14;18) translocation in follicular lymphoma
      from a cohort of a multi-ethnic Asian population. METHODS AND RESULTS: Sixty-two
      cases of follicular lymphoma were retrieved for immunohistochemistry, and
      t(14;18) translocation analysis by polymerase chain reaction and fluorescent in
      situ hybridization techniques. Bcl-2 expression was present in 74% of the cases.
      CD10 expression was also relatively low (61%), with decreasing frequency of
      expression in high-grade tumours. Bcl-6 protein was expressed in most of the
      tumours (88%) regardless of the tumour grade. The t(14;18) translocation was
      detected in 46 cases (74%) with an extremely high rate of t(14;18) translocation
      in ethnic Indian cases (100%). CONCLUSION: The frequency of t(14;18)
      translocation in this series of follicular lymphomas was higher when compared
      with previous Asian reports, but in accordance with European and North American
      findings. CD10 expression is strongly associated with a t(14;18) translocation
      event, but the overall CD10 expression was relatively low, possibly due to the
      high proportion of high-grade tumours in the series. t(14;18) translocation was
      not associated with Bcl-2 or Bcl-6 expression.

PMID- 15500655
TI  - Cellular retinol-binding protein-1 expression in endometrial stromal cells:
      physiopathological and diagnostic implications.
AB  - AIMS: Cellular retinol-binding protein-1 (CRBP-1) contributes to the maintenance
      of the differentiated state of the endometrium through retinol bioavailability
      regulation. The aim was to analyse CRBP-1 expression in endometrial stromal cells
      at eutopic and ectopic sites in different physiopathological conditions. METHODS
      AND RESULTS: Antibodies to CRBP-1, CD10 and alpha-smooth muscle actin were
      applied to proliferative (n = 10), secretory (n = 9) and atrophic (n = 7)
      endometrium, decidua (n = 4), adenomyosis (n = 5), endometriosis (n = 10),
      endometrial polyps (n = 9), simple endometrial hyperplasia (n = 6), well
      differentiated endometrioid carcinoma (n = 6) and submucosal leiomyomas (n = 5).
      In some cases, Western blotting and reverse transcription-polymerase chain
      reaction were also applied. CRBP-1 was expressed by eutopic and ectopic
      endometrial stromal cells more markedly during the late secretory phase and in
      decidua of pregnancy. CRBP-1 expression was low in the stroma of atrophic
      endometrium and absent in myometrium, leiomyomas and cervical stroma. CD10
      immunoreactivity was weak in atrophic endometrium and in decidua. CONCLUSIONS:
      CRBP-1 expression characterizes endometrial stromal cells at eutopic and ectopic
      sites and appears to be more specific than CD10. The level of CRBP-1 varies in
      intensity according to hormonal variations, reaching its maximum in predecidua
      and decidua. Thus, immunodetection of CRBP-1 may help to elucidate the
      physiopathological changes which occur in endometrial stroma and can also be
      applied as an adjuvant stromal marker.

PMID- 15500656
TI  - Extramedullary haematopoiesis in massive hepatic necrosis.
AB  - AIMS: To determine the frequency of extramedullary haematopoiesis (EMH) in
      massive hepatic necrosis (MHN). METHODS AND RESULTS: Explanted livers of 11 adult
      patients transplanted consecutively for MHN were examined histologically and
      immunohistochemically for the presence of EMH. The aetiology of the liver damage
      was unknown in seven cases and drug induced in four. The presence of stem cell
      markers (CD34, c-kit), erythroid precursors (glycophorin A), myeloid precursors
      (myeloperoxidase) and megakaryocyte precursors (CD31) was investigated by
      immunohistochemistry. Erythroid, myeloid and megakaryocyte precursors were
      observed in all cases. Morphologically, haematopoietic blast cells were clustered
      in areas of collapse, separating islands of regenerating ductules and scattered
      between ductules, in a similar distribution to immunohistochemically identified c
      kit-positive putative stem cells. No CD34+ cells other than endothelial cells
      were seen. All 11 patients were anaemic at the time of transplantation.
      CONCLUSIONS: EMH is a frequent finding in patients undergoing liver
      transplantation for MHN. This may be a consequence of the anaemia associated with
      this condition. Alternatively, the possibility that intrahepatic haematopoiesis
      is linked with hepatopoiesis is an additional, intriguing possibility that
      deserves further study.

PMID- 15500657
TI  - Lingual alveolar soft part sarcoma; 14 cases: novel clinical and morphological
      observations.
AB  - AIMS: Alveolar soft part sarcoma (ASPS) is a rare sarcoma in the buttocks or
      thigh of young adults, often with metastases to lung, brain, or bone. This study
      examines the morphological and clinical features of lingual ASPS. METHODS AND
      RESULTS: Fourteen cases, in eight males and six females (ages 3-21 years, median
      5 years), ranged from 8 to 50 mm, median 25 mm. All tumours were intramuscular,
      circumscribed and multinodular. Tumours from all but the oldest patient exhibited
      a predominantly solid (non-alveolar) growth pattern. Vascular invasion was
      common. Crystals varied in number from none or extremely rare to nearly 100% of
      tumour cells. Immunohistochemical results: Fifty percent desmin positive, all
      focally smooth muscle antigen (SMA) positive; negative for vimentin,
      neural/melanocytic, myoid, histiocytic, and epithelial markers. All tumours were
      surgically excised; only two patients received chemotherapy. Follow-up on 10
      patients showed that all patients were alive without disease (4-32, median 22
      years). Only one patient had a microscopic metastasis to lung (3 years) but was
      without disease at 11 years. CONCLUSIONS: Lingual ASPS is a tumour of childhood
      with a distinctive, predominantly solid growth pattern. Despite typical vascular
      invasion, the early diagnosis and small tumour size may explain its relatively
      good outcome.

PMID- 15500659
TI  - Unusual strong CD34 positivity in a thoracic monophasic fibrous synovial sarcoma.

PMID- 15500660
TI  - Coexistent atypical adenomatous hyperplasia, primary lung adenocarcinoma and
      pleural mesothelioma in an asbestos-exposed subject.

PMID- 15500661
TI  - Post mortem diagnosis of fatal obstructive sleep apnoea.

PMID- 15500662
TI  - Lung metastases as an initial presentation of endometrial stromal sarcoma: the
      utility of the CD10 antibody.

PMID- 15500664
TI  - A survey of occupational hand eczema in Denmark.
AB  - Occupational hand eczema (OHE) is the most frequently recognized work-related
      disease in Denmark and the annual cost to society is high. Understanding of the
      epidemiology of OHE is essential to be able to give appropriate recommendations
      for its prevention. The study comprised 758 persons, 490 females and 268 males
      with recognized OHE in the period October 2001 to November 2002. Data were
      obtained prospectively from the National Board of Industrial Industry Registry
      and from a self-administered questionnaire (response rate, 82%). The most
      frequently recognized diagnosis was irritant contact dermatitis (ICD), mainly
      caused by wet occupations. The proportion of occupational ICD was equal for males
      and females, 59.7% and 63.1%, respectively. The estimated rates of OHE were high
      for bakers, hairdressers and dental surgery assistants, and a high proportion of
      apprentices were found among hairdressers. The prevalence of atopic dermatitis
      was low (16.4%) compared to previous studies among hand eczema patients. The
      prevalence of occupational allergic contact dermatitis in the study population
      was substantially higher among males than females, and the most frequent causes
      among males were allergy to chromium (leather exposure), rubber additives
      (gloves) and nickel due to exposure from work tools and metalworking industry.

PMID- 15500665
TI  - Primula obconica--is contact allergy on the decline?
AB  - Primula obconica, a member of the Primulaceae family, was introduced to Britain
      from China in 1880. P. obconica cultivars, which are reputed to contain less
      primin, have been developed over the past number of years in an attempt to reduce
      the incidence of allergic contact dermatitis. Primin (2-methoxy-6-pentyl-1,4
      benzoquinone) is the main sensitizer, although other allergens have been
      postulated. We believe the incidence of primula allergic contact dermatitis has
      fallen since the introduction of primin-free P. obconica into the European market
      and thus the aims of this study were twofold. First, to determine whether the
      incidence of primula allergic contact dermatitis was truly on the decline and,
      second, to confirm the presence of primin-free P. obconica in the UK. We surveyed
      the incidence of primula allergic contact dermatitis in the UK and compared the
      incidence in the period between 1995 and 2000 with a subsequent follow-up study
      looking at the incidence for 2002. The results showed a significant fall in
      primin-positive patch tests from 1995 to 2000. The follow-up results for 2002
      showed a further reduction in the number of primin-positive patch tests. The
      yearly incidence of contact allergy to primin has fallen from 0.785% in 1995/1996
      to 0.429% in 2002. This downward trend was statistically significant (P = 0.001).
      A telephone survey of UK seed suppliers and selected plant retailers was also
      undertaken to clarify what types of P. obconica were available for sale and to
      assess suppliers' and retailers' knowledge of the primin-free varieties. This
      survey showed that 50% of suppliers were selling primin-free varieties but that
      the majority of surveyed retailers were not currently selling any variety of P.
      obconica. Our study suggests that although the yearly incidence of contact
      allergy to primin has fallen significantly over the past 8 years, it is still an
      important allergen, and thus its inclusion in the standard series remains
      justified for the foreseeable future.

PMID- 15500666
TI  - Patch testing with metalworking fluids from the patient's workplace.
AB  - In view of the wide variety of components currently used in metalworking fluids
      (MWF), relevant contact sensitizations may be overlooked, because commercially
      available MWF test series cannot cover the full spectrum. Hence, patch testing
      with MWF from the patient's workplace is an important additional diagnostic tool.
      However, recommendations on how to perform such patch tests vary. We
      retrospectively analyzed patch test data of the Department of Dermatology in
      Dortmund, 1992-2003. In 141 metalworkers tested because of suspected occupational
      contact dermatitis due to MWF, 829 patch tests with 306 samples of MWF were
      performed. Water-based MWF (wb MWF) were mainly tested in 2 dilution series, i.e.
      pure (workplace concentration), 10% aq. and 1% aq., and pure, 50% aq. and 10% aq.
      Positive reactions to wb MWF occurred in 27 patients. Patch testing with wb MWF
      at workplace concentration resulted in 16.1% (39/242) positive reactions, with a
      positivity ratio of 69% and a reaction index of 0. From the analysis of reaction
      patterns and concomitant reactions, we conclude that most of these positive
      reactions indicated true contact allergy. With lower concentrations, relevant
      allergic reactions may be missed. Neat oils were tested as is or diluted from 1
      to 50% in olive oil, but no reactions at all were observed. For optimum benefit
      of patch testing with MWF from the patient's workplace, breakdown testing is
      recommended. To overcome the time-consuming difficulties associated with this
      procedure, we propose a centre for information and documentation of contact
      allergies due to occupational exposure. Furthermore, full declaration of MWF
      ingredients is desirable.

PMID- 15500667
TI  - Multicentre patch test study of air-oxidized ethoxylated surfactants.
AB  - Frequent exposure to water and surfactants is considered to be the main cause of
      hand eczema from wet work. Ethoxylated surfactants are susceptible to oxidation
      and some of the oxidation products formed have proved to be contact sensitizers
      in guinea pigs. The question of human sensitization to oxidized surfactants was
      addressed in a multicentre study in the Stockholm region. 528 consecutive
      dermatitis patients were patch tested with widely used ethoxylated surfactants in
      oxidized and non-oxidized form as well as certain identified oxidation compounds.
      61 patients presented with mild, clearly irritant reactions to some of the
      surfactants tested. 18 patients showed not only erythema but also oedema and/or
      papules and vesicles, using a morphologic descriptive system for reading the
      patch test reactions. These reactions occurred mostly to oxidized surfactants and
      oxidation products. When retesting 9 of these 18 patients only an allergic
      reaction to acetaldehyde was confirmed. We conclude that oxidized ethoxylated
      surfactants have increased irritant potential compared to non-oxidized material.
      Our working hypothesis is that oxidized surfactants of technical quality exert a
      lower risk of sensitization than do oxidized homologous pure surfactants. Among
      the potential allergens formed during autoxidation, formaldehyde and acetaldehyde
      must be considered as a source of unexpected exposure.

PMID- 15500668
TI  - Compliance in contact allergy with focus on cosmetic labelling: a qualitative
      research project.
AB  - Elimination of the allergen is an effective remedy in allergic contact
      dermatitis. When contact allergy to a preservative is diagnosed, the patient is
      instructed to read the labelling of contents and to avoid the use of products
      containing the allergens. The present study, using qualitative research methods,
      was performed to examine how socially different groups of patients handle
      everyday life with allergic contact dermatitis caused by preservatives in
      consumer products. 8 women were interviewed about reading the ingredient
      labelling on cosmetic products. Observational studies were carried out as well.
      The study illustrates that the patients experienced problems when trying to read
      the labelling of contents. The problems were related to social status and ranged
      from not being able to read the chemical names of the preservatives to doubting
      the accuracy of the ingredient labelling. The study indicates that non-compliance
      with instructions on reading the ingredient labelling is not only a question of
      patients' lack of knowledge, but also the result of patients not possessing the
      resources necessary to act in accordance with the medical instructions. The
      present study is, to our knowledge, the first to apply qualitative research
      methods to contact dermatitis. The study points out interesting observations
      about social status and resources in relation to compliance. Further research on
      this area is necessary to expose the extent of the problem.

PMID- 15500669
TI  - Human scalp irritation compared to that of the arm and back.
AB  - Large-scale data comparing reactions to surfactants between scalp and back and
      arm are lacking. The sensitivity of responses between scalp and back and arm were
      explored utilizing an open-application model for testing the potential irritancy
      of sodium lauryl sulphate (SLS). 10 bald male Caucasians (mean age 56 +/- 9
      years) were enrolled. We conducted 5 successive washings: for each wash, the
      technician pipetted 1 ml of 20% SLS solution into a glass cylinder placed on the
      designated area with hand pressure that prevented the cylinder leaking. The test
      area was then rubbed with a Teflon Policeman scrubber for 1 min. Post scrubbing,
      the solution was absorbed dry with a plastic pipette and blotted by gently
      applying paper tissues. After a 5-min rest, the procedure was repeated for 4 more
      times for a total of 5 times. Skin-irritancy assessments by visual scoring and
      instrumental measurements were made at 30 min and 24 h thereafter and squamometry
      at the end of last washing. Results indicated that most param- eters revealed
      that the back was most sensitive to the SLS challenge. Thus, these data support
      the current standard skin-compatibility testing procedure, employing the back for
      potential irritation testing of hair care products.

PMID- 15500670
TI  - The vulvar epithelium differs from the skin: implications for cutaneous testing
      to address topical vulvar exposures.
AB  - Vulvar tissue is more permeable than exposed skin due to differences in
      structure, occlusion, hydration and susceptibility to friction. The safety
      assessment of products that contact the vulva should account for this potentially
      heightened permeability. Standard clinical patch tests may not sufficiently mimic
      vulvar exposures. Because testing on the vulva is not routinely feasible, we are
      investigating new and modified cutaneous test methods to increase the degree of
      conservatism of the safety assessment. To this end, we have 1) developed a method
      to assess chemical and frictional effects by means of repeated application to the
      popliteal fossa (the behind-the-knee test); 2) modified the quantitative risk
      assessment for the induction of allergic contact dermatitis; and 3) proposed a
      modified human repeat insult patch test for assessing materials intended for
      vulvar contact. Modification of the traditional 4-day, irritation patch test by
      using wet samples or compromized skin sites failed to enhance test sensitivity.
      Future studies will evaluate testing in subjects with heightened susceptibility
      to chemical and sensory irritation, in order to increase test sensitivity to
      chemical irritants. These approaches can be employed to augment the margin of
      safety when cutaneous test methods are applied to agents that contact the vulva.

PMID- 15500671
TI  - The clinicopathological characteristics of oral lichen planus and its
      relationship with dental materials.
AB  - The objective of this work was to carry out a clinicopathological study to
      ascertain whether clinical and histopathologic differences existed between oral
      lichen planus OLP patients with and without metal restorations. The predominant
      clinical form in both groups was reticular white, with no statistically
      significant differences between the forms associated or not with metal. The
      histological variables showed no statistically significant differences between
      the groups.

PMID- 15500672
TI  - Widespread contact dermatitis from tocopherol acetate.

PMID- 15500673
TI  - Allergic contact dermatitis from N-(cyclohexylthio) phthalimide in a playground
      fitter.

PMID- 15500674
TI  - A new approach to patch testing patients with para-phenylenediamine allergy
      secondary to temporary black henna tattoos.

PMID- 15500675
TI  - Kobnerizing occupational contact allergy to thiuram in a farmer with psoriasis.

PMID- 15500676
TI  - Localized recurrence of chromate dermatitis.

PMID- 15500677
TI  - Contact dermatitis from 3 different allergens in Solaraze gel.

PMID- 15500678
TI  - Allergic contact dermatitis from tamanu oil (Calophyllum inophyllum, Calophyllum
      tacamahaca).

PMID- 15500679
TI  - Contact dermatitis from the staples of neuroreflexotherapy.

PMID- 15500681
TI  - Detecting imbalanced expression of SNP alleles by minisequencing on microarrays.
AB  - BACKGROUND: Each of the human genes or transcriptional units is likely to contain
      single nucleotide polymorphisms that may give rise to sequence variation between
      individuals and tissues on the level of RNA. Based on recent studies,
      differential expression of the two alleles of heterozygous coding single
      nucleotide polymorphisms (SNPs) may be frequent for human genes. Methods with
      high accuracy to be used in a high throughput setting are needed for systematic
      surveys of expressed sequence variation. In this study we evaluated two formats
      of multiplexed, microarray based minisequencing for quantitative detection of
      imbalanced expression of SNP alleles. We used a panel of ten SNPs located in five
      genes known to be expressed in two endothelial cell lines as our model system.
      RESULTS: The accuracy and sensitivity of quantitative detection of allelic
      imbalance was assessed for each SNP by constructing regression lines using a
      dilution series of mixed samples from individuals of different genotype. Accurate
      quantification of SNP alleles by both assay formats was evidenced for by R2
      values > 0.95 for the majority of the regression lines. According to a two sample
      t-test, we were able to distinguish 1-9% of a minority SNP allele from a
      homozygous genotype, with larger variation between SNPs than between assay
      formats. Six of the SNPs, heterozygous in either of the two cell lines, were
      genotyped in RNA extracted from the endothelial cells. The coefficient of
      variation between the fluorescent signals from five parallel reactions was
      similar for cDNA and genomic DNA. The fluorescence signal intensity ratios
      measured in the cDNA samples were compared to those in genomic DNA to determine
      the relative expression levels of the two alleles of each SNP. Four of the six
      SNPs tested displayed a higher than 1.4-fold difference in allelic ratios between
      cDNA and genomic DNA. The results were verified by allele-specific
      oligonucleotide hybridisation and minisequencing in a microtiter plate format.
      CONCLUSIONS: We conclude that microarray based minisequencing is an accurate and
      accessible tool for multiplexed screening for imbalanced allelic expression in
      multiple samples and tissues in parallel.

PMID- 15500683
TI  - Improving epidemic malaria planning, preparedness and response in Southern
      Africa. Report on the 1st Southern African Regional Epidemic Outlook Forum,
      Harare, Zimbabwe, 26-29 September, 2004.
AB  - Malaria is a major public health problem for countries in the Southern Africa
      Development Community (SADC). While the endemicity of malaria varies enormously
      across this region, many of the countries have districts that are prone to
      periodic epidemics, which can be regional in their extent, and to resurgent
      outbreaks that are much more localized. These epidemics are frequently triggered
      by climate anomalies and often follow periods of drought. Many parts of Southern
      Africa have suffered rainfall deficit over the past three years and countries
      expect to see increased levels of malaria when the rains return to more 'normal'
      levels. Problems with drug and insecticide resistance are documented widely and
      the region contains countries with the highest rates of HIV prevalence to be
      found anywhere in the world. Consequently, many communities are vulnerable to
      severe disease outcomes should epidemics occur. The SADC countries have adopted
      the Abuja targets for Roll Back Malaria in Africa, which include improved
      epidemic detection and response, i.e., that 60% of epidemics will be detected
      within two weeks of onset, and 60% of epidemics will be responded to within two
      weeks of detection. The SADC countries recognize that to achieve these targets
      they need improved information on where and when to look for epidemics. The WHO
      integrated framework for improved early warning and early detection of malaria
      epidemics has been recognized as a potentially useful tool for epidemic
      preparedness and response planning. Following evidence of successful adoption and
      implementation of this approach in Botswana, the SADC countries, the WHO Southern
      Africa Inter-Country Programme on Malaria Control, and the SADC Drought
      Monitoring Centre decided to organize a regional meeting where countries could
      gather to assess their current control status and community vulnerability,
      consider changes in epidemic risk, and develop a detailed plan of action for the
      forthcoming 2004-2005 season. The following is a report on the 1st Southern
      African Regional Epidemic Outlook Forum, which was held in Harare, Zimbabwe, 26th
      29th September, 2004.

PMID- 15500682
TI  - Enhanced cell-permeant Cre protein for site-specific recombination in cultured
      cells.
AB  - BACKGROUND: Cell-permeant Cre DNA site-specific recombinases provide an easily
      controlled means to regulate gene structure and function in living cells. Since
      recombination provides a stable and unambiguous record of protein uptake, the
      enzyme may also be used for quantitative studies of cis- and trans-acting factors
      that influence the delivery of proteins into cells. RESULTS: In the present
      study, 11 recombinant fusion proteins were analyzed to characterize sequences and
      conditions that affect protein uptake and/or activity and to develop more active
      cell-permeant enzymes. We report that the native enzyme has a low, but intrinsic
      ability to enter cells. The most active Cre proteins tested contained either an N
      terminal 6xHis tag and a nuclear localization sequence from SV40 large T antigen
      (HNC) or the HIV Tat transduction sequence and a C-terminal 6xHis tag (TCH6). The
      NLS and 6xHis elements separately enhanced the delivery of the HNC protein into
      cells; moreover, transduction sequences from fibroblast growth factor 4, HIV Tat
      or consisting of the (KFF)3K sequence were not required for efficient protein
      transduction and adversely affected enzyme solubility. Transduction of the HNC
      protein required 10 to 15 min for half-maximum uptake, was greatly decreased at 4
      degrees C and was inhibited by serum. Efficient recombination was observed in all
      cell types tested (a T-cell line, NIH3T3, Cos7, murine ES cells, and primary
      splenocytes), and did not require localization of the enzyme to the nucleus.
      CONCLUSIONS: The effects of different sequences on the delivery and/or activity
      of Cre in cultured cells could not be predicted in advance. Consequently, the
      process of developing more active cell-permeant recombinases was largely
      empirical. The HNC protein, with an excellent combination of activity, solubility
      and yield, will enhance the use of cell-permeant Cre proteins to regulate gene
      structure and function in living cells.

PMID- 15500684
TI  - Brain inflammation and oxidative stress in a transgenic mouse model of Alzheimer
      like brain amyloidosis.
AB  - BACKGROUND: An increasing body of evidence implicates both brain inflammation and
      oxidative stress in the pathogenesis of Alzheimer's disease (AD). The relevance
      of their interaction in vivo, however, is unknown. Previously, we have shown that
      separate pharmacological targeting of these two components results in
      amelioration of the amyloidogenic phenotype of a transgenic mouse model of AD
      like brain amyloidosis (Tg2576). METHODS: In the present study, we investigated
      the therapeutic effects of a combination of an anti-inflammatory agent,
      indomethacin, and a natural anti-oxidant, vitamin E, in the Tg2576 mice. For this
      reason, animals were treated continuously from 8 (prior to Abeta deposition)
      through 15 (when Abeta deposits are abundant) months of age. RESULTS: At the end
      of the study, these therapeutic interventions suppressed brain inflammatory and
      oxidative stress responses in the mice. This effect was accompanied by
      significant reductions of soluble and insoluble Abeta1-40 and Abeta1-42 in
      neocortex and hippocampus, wherein the burden of Abeta deposits also was
      significantly decreased. CONCLUSIONS: The results of the present study support
      the concept that brain oxidative stress and inflammation coexist in this animal
      model of AD-like brain amyloidosis, but they represent two distinct therapeutic
      targets in the disease pathogenesis. We propose that a combination of anti
      inflammatory and anti-oxidant drugs may be a useful strategy for treating AD.

PMID- 15500685
TI  - Atherosclerosis of the descending aorta predicts cardiovascular events: a
      transesophageal echocardiography study.
AB  - PURPOSE: Previous studies have shown that atherosclerosis of the descending aorta
      detected by transesophageal echocardiography (TEE) is a good marker of coexisting
      coronary artery disease. The aim of our study was to evaluate whether the
      presence of atherosclerosis on the descending aorta during TEE has any prognostic
      impact in predicting cardiovascular events. MATERIAL AND METHODS: The study group
      consisted of 238 consecutive in-hospital patients referred for TEE testing (135
      males, 103 females, mean age 58 +/- 11 years) with a follow up of 24 months. The
      atherosclerotic lesions of the descending aorta were scored from 0 (no
      atherosclerosis) to 3 (plaque >5 mm and/or "complex" plaque with ulcerated or
      mobile parts). RESULTS: Atherosclerosis was observed in 102 patients, (grade 3 in
      16, and grade 2 in 86 patients) whereas 136 patients only had an intimal
      thickening or normal intimal surface. There were 57 cardiovascular events in the
      follow-up period. The number of events was higher in the 102 patients with (n =
      34) than in the 136 patients without atherosclerosis (n = 23, p < 0.01). The
      frequency of events was in close correlation with the severity of the
      atherosclerosis of the descending aorta. Fifty percent of the patients with grade
      3 experienced cardiovascular events. Excluding patients with subsequent
      revascularization, the multivariate analysis only left ventricular function with
      EF < 40% (HR 3.0, CI 1.3-7.1) and TEE atherosclerotic plaque >=2 (HR 2.4, CI 1.0
      5.5) predicted hard cardiovascular events. CONCLUSION: Atherosclerosis of the
      descending aorta observed during transesophageal echocardiography is a useful
      predictor of cardiovascular events.

PMID- 15500687
TI  - Assessment of the dynamics of atrial signals and local atrial period series
      during atrial fibrillation: effects of isoproterenol administration.
AB  - BACKGROUND: The autonomic nervous system (ANS) plays an important role in the
      genesis and maintenance of atrial fibrillation (AF), but quantification of its
      electrophysiologic effects is extremely complex and difficult. Aim of the study
      was to evaluate the capability of linear and non-linear indexes to capture the
      fine changing dynamics of atrial signals and local atrial period (LAP) series
      during adrenergic activation induced by isoproterenol (a sympathomimetic drug)
      infusion. METHODS: Nine patients with paroxysmal or persistent AF (aged 60 +/- 6)
      underwent electrophysiological study in which isoproterenol was administered to
      patients. Atrial electrograms were acquired during i) sinus rhythm (SR); ii)
      sinus rhythm during isoproterenol (SRISO) administration; iii) atrial
      fibrillation (AF) and iv) atrial fibrillation during isoproterenol (AFISO)
      administration. The level of organization between two electrograms was assessed
      by the synchronization index (S), whereas the degree of recurrence of a pattern
      in a signal was defined by the regularity index (R). In addition, the level of
      predictability (LP) and regularity of LAP series were computed. RESULTS: LAP
      series analysis shows a reduction of both LP and R index during isoproterenol
      infusion in SR and AF (RSR = 0.75 +/- 0.07 RSRISO = 0.69 +/- 0.10, p < 0.0001;
      RAF = 0.31 +/- 0.08 RAFISO = 0.26 +/- 0.09, p < 0.0001; LPSR = 99.99 +/- 0.001
      LPSRISO = 99.97 +/- 0.03, p < 0.0001; LPAF = 69.46 +/- 21.55 LPAFISO = 55 +/-
      24.75; p < 0.0001). Electrograms analysis shows R index reductions both in SR
      (RSR = 0.49 +/- 0.08 RSRISO = 0.46 +/- 0.09 p < 0.0001) and in AF (RAF = 0.29 +/-
      0.09 RAFISO = 0.28 +/- 0.08 n.s.). CONCLUSIONS: The proposed parameters succeeded
      in discriminating the subtle changes due to isoproterenol infusion during both
      the rhythms especially when considering LAP series analysis. The reduced value of
      analyzed parameters after isoproterenol administration could reflect an important
      pro-arrhythmic influence of adrenergic activation on favoring maintenance of AF.

PMID- 15500686
TI  - Factors involved in the inflammatory events of cervical ripening in humans.
AB  - BACKGROUND: Cervical ripening is an inflammatory reaction. The glucocorticoid
      receptor (GR) mediates glucocorticoid anti-inflammatory reactions, whereas
      nuclear factor (NF)kappaB is a key pro-inflammatory transcription factor.
      Prostaglandins as well as platelet activating factor (PAF) are inflammatory
      mediators. Inducible nitric oxide synthase (iNOS) regulates the level of nitric
      oxide (NO) in response to various inflammatory stimuli. We hypothesize that a
      changed biological response to glucocorticoids could be a mechanism regulating
      the inflammatory events resulting in cervical ripening. METHODS: We monitored GR
      and NFkappaB, prostaglandin synthases cyclooxygenase (COX)-1 and -2, iNOS, as
      well as the PAF-receptor (PAF-R) in the uterine cervix from term pregnant women
      (with unripe cervices) before the onset of labor (TP), immediately after
      parturition (PP), as compared to non-pregnant (NP), using immunohistochemistry
      and RT-PCR. RESULTS: The GR protein was detected by immunohistochemistry in the
      nuclei of stroma and squamous epithelium (SQ). Stromal GR staining was increased
      in TP as compared to the NP group and decreased again after parturition. GR
      staining in SQ was decreased after parturition as compared to term. NFkappaB was
      present in SQ and glandular epithelium (GE), stroma and vascular endothelium.
      Increased nuclear NFkappaB staining was observed postpartum as compared to term
      pregnancy in stroma and GE. Stromal immunostaining for COX-1 as well as COX-2 was
      increased in the TP and PP groups as compared to the NP, and GE displayed an
      intensely increased COX-2 immunostaining at term and postpartum. Stromal PAF-R
      immunostaining was highest at term, while it was greatly increased in GE
      postpartum. No difference in the immunostaining for iNOS was found between the
      groups. RT-PCR showed a predominance of GRalpha to GRbeta mRNA in cervical
      tissue. The COX-2 mRNA level was increased in the PP group as compared to the TP
      group. CONCLUSIONS: There is a decrease in GR levels in human cervix at
      parturition. Concomitantly there is an increase of factors such as NFkappaB, PAF
      R, COX-1 and COX-2, suggesting that they may participate in the sequence of
      events leading to the final cervical ripening.

PMID- 15500688
TI  - Killing Bugs at the Bedside: a prospective hospital survey of how frequently
      personal digital assistants provide expert recommendations in the treatment of
      infectious diseases.
AB  - BACKGROUND: Personal Digital Assistants (PDAS) are rapidly becoming popular tools
      in the assistance of managing hospitalized patients, but little is known about
      how often expert recommendations are available for the treatment of infectious
      diseases in hospitalized patients. OBJECTIVE: To determine how often PDAs could
      provide expert recommendations for the management of infectious diseases in
      patients admitted to a general medicine teaching service. DESIGN: Prospective
      observational cohort study SETTING: Internal medicine resident teaching service
      at an urban hospital in Dayton, Ohio PATIENTS: 212 patients (out of 883 patients
      screened) were identified with possible infectious etiologies as the cause for
      admission to the hospital. MEASUREMENTS: Patients were screened prospectively
      from July 2002 until October 2002 for infectious conditions as the cause of their
      admissions. 5 PDA programs were assessed in October 2002 to see if treatment
      recommendations were available for managing these patients. The programs were
      then reassessed in January 2004 to evaluate how the latest editions of the
      software would perform under the same context as the previous year. RESULTS: PDAs
      provided treatment recommendations in at least one of the programs for 100% of
      the patients admitted over the 4 month period in the 2004 evaluation. Each of the
      programs reviewed improved from 2002 to 2004, with five of the six programs
      offering treatment recommendations for over 90% of patients in the study.
      CONCLUSION: Current PDA software provides expert recommendations for a great
      majority of general internal medicine patients presenting to the hospital with
      infectious conditions.

PMID- 15500689
TI  - Decrease of resistance to air flow with nasal strips as measured with the airflow
      perturbation device.
AB  - BACKGROUND: Nasal strips are used by athletes, people who snore, and asthmatics
      to ease the burden of breathing. Although there are some published studies that
      demonstrate higher flow with nasal strips, none had directly measured the effect
      of the strips on nasal resistance using the airflow perturbation device (APD).
      The APD is an inexpensive instrument that can measure respiratory resistance
      based on changes in mouth pressure and rate of airflow. METHOD: This study tested
      forty-seven volunteers (14 men and 33 women), ranging in age from 17 to 51. Each
      volunteer was instructed to breathe normally into the APD using an oronasal mask
      with and without nasal strips. The APD measured respiratory resistance during
      inhalation, exhalation, and an average of the two. RESULTS: Results of a paired
      mean t-test comparing nasal strip against no nasal strip were statistically
      significant at the p = 0.05 level. The Breathe Right nasal dilator strips lowered
      nasal resistance by an average of 0.5 cm H20/Lps from an average nasal resistance
      of 5.5 cm H20/Lps. CONCLUSIONS: Nasal strips reduce nasal resistance when
      measured with the APD. The effect is equal during exhalation and during
      inhalation.

PMID- 15500690
TI  - Acetylcysteine for prevention of contrast-induced nephropathy after intravascular
      angiography: a systematic review and meta-analysis.
AB  - BACKGROUND: Contrast-induced nephropathy is an important cause of acute renal
      failure. We assess the efficacy of acetylcysteine for prevention of contrast
      induced nephropathy among patients undergoing intravascular angiography. METHODS:
      We conducted a systematic review and meta-analysis of randomized controlled
      trials comparing prophylactic acetylcysteine plus hydration versus hydration
      alone in patients undergoing intravascular angiography. Studies were identified
      by searching MEDLINE, EMBASE, and CENTRAL databases. Our main outcome measures
      were the risk of contrast-induced nephropathy and the difference in serum
      creatinine between acetylcysteine and control groups at 48 h. RESULTS: Fourteen
      studies involving 1261 patients were identified and included for analysis, and
      findings were heterogeneous across studies. Acetylcysteine was associated with a
      significantly reduced incidence of contrast-induced nephropathy in five studies,
      and no difference in the other nine (with a trend toward a higher incidence in
      six of the latter studies). The pooled odds ratio for contrast-induced
      nephropathy with acetylcysteine relative to control was 0.54 (95% CI, 0.32-0.91,
      p = 0.02) and the pooled estimate of difference in 48-h serum creatinine for
      acetylcysteine relative to control was -7.2 mumol/L (95% CI -19.7 to 5.3, p =
      0.26). These pooled values need to be interpreted cautiously because of the
      heterogeneity across studies, and due to evidence of publication bias. Meta
      regression suggested that the heterogeneity might be partially explained by
      whether the angiography was performed electively or as emergency. CONCLUSION:
      These findings indicate that published studies of acetylcysteine for prevention
      of contrast-induced nephropathy yield inconsistent results. The efficacy of
      acetylcysteine will remain uncertain unless a large well-designed multi-center
      trial is performed.

PMID- 15500691
TI  - Adjuvant interferon gamma in patients with drug - resistant pulmonary
      tuberculosis: a pilot study.
AB  - BACKGROUND: Tuberculosis (TB) is increasing in the world and drug-resistant (DR)
      disease beckons new treatments. METHODS: To evaluate the action of interferon
      (IFN) gamma as immunoadjuvant to chemotherapy on pulmonary DR-TB patients, a
      pilot, open label clinical trial was carried out in the Cuban reference ward for
      the management of this disease. The eight subjects existing in the country at the
      moment received, as in-patients, 1 x 10(6) IU of recombinant human IFN gamma
      intramuscularly, daily for one month and then three times per week up to 6 months
      as adjuvant to the indicated chemotherapy, according to their antibiograms and
      WHO guidelines. Sputum samples collection for direct smear observation and
      culture as well as routine clinical and thorax radiography assessments were done
      monthly. RESULTS: Sputum smears and cultures became negative for acid-fast
      bacilli before three months of treatment in all patients. Lesion size was reduced
      at the end of 6 months treatment; the lesions disappeared in one case. Clinical
      improvement was also evident; body mass index increased in general. Interferon
      gamma was well tolerated. Few adverse events were registered, mostly mild; fever
      and arthralgias prevailed. CONCLUSIONS: These data suggest that IFN gamma is
      useful and well tolerated as adjunctive therapy in patients with DR-TB. Further
      controlled clinical trials are encouraged.

PMID- 15500692
TI  - Readmission and overstay after day case nasal surgery.
AB  - BACKGROUND: A readmission is classified as a patient necessitating readmission to
      hospital due to a post-operative complication following discharge. An overstay
      however, is classified as a patient having to stay longer than the planned
      duration in hospital (not having been discharged in the interim) due to a post
      operative complication. This study aims to investigate patient-related factors
      that predispose to readmission or overstay and thus make recommendations to
      decrease the likelihood of readmission or overstay. METHOD: In this retrospective
      study 312 'day-case nasal procedures', were selected from a total cohort of 4274
      ENT patients over a 17-month period. This sub-group was investigated for a range
      of demographic factors including, age, gender and ethnicity with regards to their
      relationship to readmission rates and overstay frequency and duration. RESULTS:
      The rates were 2.88% and 9.62% for readmission and overstay respectively. The
      total number of days spent in hospital as a result of readmission was 27.
      Epistaxis was the leading cause for readmission/overstay (28.9%) followed by high
      levels of post-operative pain preventing them from being discharged (23.7%). All
      procedures in this study had readmission rates that were below those recommended
      in the guidelines set by the Royal College of Surgeons of England. Women
      overstayed significantly longer (t = 1.65, p < 0.05) than men. CONCLUSIONS:
      Suitable candidates for day-case ENT surgery highlighted by this study include
      healthy individuals between the ages of 20 and 60. Operating in the morning would
      increase the immediate post-operative recovery time, which may reduce the numbers
      of patients who complain of high levels of pain at the time of discharge.
      Procedures such as septorhinoplasty being performed routinely in the ambulatory
      setting require additional research into more effective methods of pain control.
      Standards need to be improved so that the causes of overstay and readmission are
      clearly identifiable in patient records.

PMID- 15500693
TI  - Development of the time course for processing conflict: an event-related
      potentials study with 4 year olds and adults.
AB  - BACKGROUND: Tasks involving conflict are widely used to study executive
      attention. In the flanker task, a target stimulus is surrounded by distracting
      information that can be congruent or incongruent with the correct response.
      Developmental differences in the time course of brain activations involved in
      conflict processing were examined for 22 four year old children and 18 adults.
      Subjects performed a child-friendly flanker task while their brain activity was
      registered using a high-density electroencephalography system. RESULTS: General
      differences were found in the amplitude and time course of event-related
      potentials (ERPs) between children and adults that are consistent with their
      differences in reaction time. In addition, the congruency of flankers affected
      both the amplitude and latency of some of the ERP components. These effects were
      delayed and sustained for longer periods of time in the children compared to the
      adults. CONCLUSIONS: These differences constitute neural correlates of children's
      greater difficulty in monitoring and resolving conflict in this and similar
      tasks.

PMID- 15500695
TI  - Mental health first aid training of the public in a rural area: a cluster
      randomized trial [ISRCTN53887541].
AB  - BACKGROUND: A Mental Health First Aid course has been developed which trains
      members of the public in how to give initial help in mental health crisis
      situations and to support people developing mental health problems. This course
      has previously been evaluated in a randomized controlled trial in a workplace
      setting and found to produce a number of positive effects. However, this was an
      efficacy trial under relatively ideal conditions. Here we report the results of
      an effectiveness trial in which the course is given under more typical
      conditions. METHODS: The course was taught to members of the public in a large
      rural area in Australia by staff of an area health service. The 16 Local
      Government Areas that made up the area were grouped into pairs matched for size,
      geography and socio-economic level. One of each Local Government Area pair was
      randomised to receive immediate training while one served as a wait-list control.
      There were 753 participants in the trial: 416 in the 8 trained areas and 337 in
      the 8 control areas. Outcomes measured before the course started and 4 months
      after it ended were knowledge of mental disorders, confidence in providing help,
      actual help provided, and social distance towards people with mental disorders.
      The data were analysed taking account of the clustered design and using an
      intention-to-treat approach. RESULTS: Training was found to produce significantly
      greater recognition of the disorders, increased agreement with health
      professionals about which interventions are likely to be helpful, decreased
      social distance, increased confidence in providing help to others, and an
      increase in help actually provided. There was no change in the number of people
      with mental health problems that trainees had contact with nor in the percentage
      advising someone to seek professional help. CONCLUSIONS: Mental Health First Aid
      training produces positive changes in knowledge, attitudes and behaviour when the
      course is given to members of the public by instructors from the local health
      service.

PMID- 15500694
TI  - The structurally constrained protein evolution model accounts for sequence
      patterns of the LbetaH superfamily.
AB  - BACKGROUND: Structure conservation constrains evolutionary sequence divergence,
      resulting in observable sequence patterns. Most current models of protein
      evolution do not take structure into account explicitly, being unsuitable for
      investigating the effects of structure conservation on sequence divergence. To
      this end, we recently developed the Structurally Constrained Protein Evolution
      (SCPE) model. The model starts with the coding sequence of a protein with known
      three-dimensional structure. At each evolutionary time-step of an SCPE
      simulation, a trial sequence is generated by introducing a random point mutation
      in the current coding DNA sequence. Then, a "score" for the trial sequence is
      calculated and the mutation is accepted only if its score is under a given
      cutoff, lambda. The SCPE score measures the distance between the trial sequence
      and a given reference sequence, given the structure. In our first brief report we
      used a "global score", in which the same reference sequence, the ancestral one,
      was used at each evolutionary step. Here, we introduce a new scoring function,
      the "local score", in which the sequence accepted at the previous evolutionary
      time-step is used as the reference. We assess the model on the UDP-N
      acetylglucosamine acyltransferase (LPXA) family, as in our previous report, and
      we extend this study to all other members of the left-handed parallel beta helix
      fold (LbetaH) superfamily whose structure has been determined. RESULTS: We
      studied site-dependent entropies, amino acid probability distributions, and
      substitution matrices predicted by SCPE and compared with experimental data for
      several members of the LbetaH superfamily. We also evaluated structure
      conservation during simulations. Overall, SCPE outperforms JTT in the description
      of sequence patterns observed in structurally constrained sites. Maximum
      Likelihood calculations show that the local-score and global-score SCPE
      substitution matrices obtained for LPXA outperform the JTT model for the LPXA
      family and for the structurally constrained sites of class i of other members
      within the LbetaH superfamily. CONCLUSION: We extended the SCPE model by
      introducing a new scoring function, the local score. We performed a thorough
      assessment of the SCPE model on the LPXA family and extended it to all other
      members of known structure of the LbetaH superfamily.

PMID- 15500696
TI  - The development of a strategy for tackling health inequalities in the
      Netherlands.
AB  - Over the past decade, the Dutch government has pursued a research-based approach
      to tackle socioeconomic inequalities in health. We report on the most recent
      phase in this approach: the development of a strategy to reduce health
      inequalities in the Netherlands by an independent committee. In addition, we will
      reflect on the way the report of this committee has influenced health policy and
      practice.A 6-year research and development program was conducted which covered a
      number of different policy options and consisted of 12 intervention studies. The
      study results were discussed with experts and policy makers. A government
      advisory committee developed a comprehensive strategy that intends to reduce
      socioeconomic inequalities in disability-free life expectancy by 25% in 2020. The
      strategy covers 4 different entry-points for reducing socioeconomic inequalities
      in health, contains 26 specific recommendations, and includes 11 quantitative
      policy targets. Further research and development efforts are also
      recommended.Although the Dutch approach has been influenced by similar efforts in
      other European countries, particularly the United Kingdom and Sweden, it is
      unique in terms of its emphasis on building a systematic evidence-base for
      interventions and policies to reduce health inequalities. Both researchers and
      policy-makers were involved in the process, and there are clear indications that
      some of the recommendations are being adopted by health policy-makers and health
      care practice, although more so at the local than at the national level.

PMID- 15500697
TI  - Clinical and inheritance profiles of Kallmann syndrome in Jordan.
AB  - BACKGROUND: Proper management of patients with Kallmann syndrome (KS) allows them
      to attain a normal reproductive health. The purpose of this study is to
      demonstrate the presentation modalities, phenotypes and the modes of inheritance
      among 32 patients with Kallmann syndrome in Jordan. Recognition of the syndrome
      allows for prompt proper management and provision of genetic counselling.
      SUBJECTS: Over a period of five years (1999-2004), the clinical and inheritance
      profiles of 26 male and 6 female patients with Kallmann syndrome from 12 families
      were evaluated at the National Center for Diabetes, Endocrinology and Genetics in
      Jordan. RESULTS: The patients belonged to twelve Jordanian and Palestinian
      families and their age at presentation ranged from 4 - 46 years. Nine boys aged 4
      14 years presented with cryptorchidism and microphallus, all other males
      presented with delayed puberty, hypogonadism and/or infertility. The main
      presentation among six female patients was primary amenorrhea. Intrafamilial
      variability in clinical phenotype was specifically evident for renal
      abnormalities and sensorineural hearing impairment. Familial KS was diagnosed in
      27 patients belonging to five families with the X-linked mode of inheritance and
      two families with the autosomal recessive mode of inheritance. CONCLUSIONS: (1)
      the majority of cases in this study represented the X-linked form of KS, which
      might point to a high prevalence of Kal 1 gene in the population. (2) Genetic
      counselling helps these families to reach a diagnosis at an early age and to
      decide about their reproductive options. (3) Children presenting with
      cryptorchidism and microphallus in our population should be investigated for KS.

PMID- 15500698
TI  - Mapping the brain's orchestration during speech comprehension: task-specific
      facilitation of regional synchrony in neural networks.
AB  - BACKGROUND: How does the brain convert sounds and phonemes into comprehensible
      speech? In the present magnetoencephalographic study we examined the hypothesis
      that the coherence of electromagnetic oscillatory activity within and across
      brain areas indicates neurophysiological processes linked to speech
      comprehension. RESULTS: Amplitude-modulated (sinusoidal 41.5 Hz) auditory verbal
      and nonverbal stimuli served to drive steady-state oscillations in neural
      networks involved in speech comprehension. Stimuli were presented to 12 subjects
      in the following conditions (a) an incomprehensible string of words, (b) the same
      string of words after being introduced as a comprehensible sentence by proper
      articulation, and (c) nonverbal stimulations that included a 600-Hz tone, a
      scale, and a melody. Coherence, defined as correlated activation of magnetic
      steady state fields across brain areas and measured as simultaneous activation of
      current dipoles in source space (Minimum-Norm-Estimates), increased within left-
      temporal-posterior areas when the sound string was perceived as a comprehensible
      sentence. Intra-hemispheric coherence was larger within the left than the right
      hemisphere for the sentence (condition (b) relative to all other conditions), and
      tended to be larger within the right than the left hemisphere for nonverbal
      stimuli (condition (c), tone and melody relative to the other conditions),
      leading to a more pronounced hemispheric asymmetry for nonverbal than verbal
      material. CONCLUSIONS: We conclude that coherent neuronal network activity may
      index encoding of verbal information on the sentence level and can be used as a
      tool to investigate auditory speech comprehension.

PMID- 15500699
TI  - Granzyme B; the chalk-mark of a cytotoxic lymphocyte.
AB  - During cytotoxic lymphocyte (CL) mediated killing of target cells, granzyme B is
      released from the CL into the immune synapse. Recent studies have found that
      ELISPOT-detection of granzyme B correlated well with conventional assays for CL
      mediated killing. In this way, the released granzyme B can be used to mark the
      spot where a target cell was murdered. We discuss the benefits and potential
      limitations of using this assay to measure CL mediated killing of target cells.

PMID- 15500700
TI  - Predicting gender differences as latent variables: summed scores, and individual
      item responses: a methods case study.
AB  - BACKGROUND: Modeling latent variables such as physical disability is challenging
      since its measurement is performed through proxies. This poses significant
      methodological challenges. The objective of this article is to present three
      different methods to predict latent variables based on classical summed scores,
      individual item responses, and latent variable models. METHODS: This is a review
      of the literature and data analysis using "layers of information". Data was
      collected from the North Carolina Back Pain Project, using a modified version of
      the Roland Questionnaire. RESULTS: The three models are compared in relation to
      their goals and underlying concepts, previous clinical applications, data
      requirements, statistical theory, and practical applications. Initial linear
      regression models demonstrated a difference in disability between genders of 1.32
      points (95% CI 0.65, 2.00) on a scale from 0-23. Subsequent item analysis found
      contradictory results across items, with no clear pattern. Finally, IRT models
      demonstrated three items were demonstrated to present differential item
      functioning. After these items were removed, the difference between genders was
      reduced to 0.78 points (95% CI, -0.99, 1.23). These results were shown to be
      robust with re-sampling methods. CONCLUSIONS: Purported differences in the levels
      of a latent variable should be tested using different models to verify whether
      these differences are real or simply distorted by model assumptions.

PMID- 15500701
TI  - CytoJournal joins 'open access' philosophy.
AB  - Welcome to CytoJournal! We would like to introduce you to your journal, one that
      is run by and for the scientific cytopathology community with incontestable
      benefits of Open Access, and support from Cytopathology Fondation, Inc
      http://www.cytopathology-foundation.org/index.html. CytoJournal is a peer
      reviewed, PubMed indexed, online journal, publishing research in the field of
      cytopathology and related areas, with world wide free access. Authors submitting
      to CutoJournal retain the copyright to their hard earned work.

PMID- 15500702
TI  - Optimization of an immunostaining protocol for the rapid intraoperative
      evaluation of melanoma sentinel lymph node imprint smears with the 'MCW melanoma
      cocktail'
AB  - BACKGROUND: In the management of cutaneous melanoma, it is desirable to complete
      the regional lymphadenectomy during the initial surgical procedure for wide
      excision of biopsy site and sentinel lymph node (SLN) biopsy. In this study, we
      optimized and evaluated a rapid 17 minutes immunostaining protocol. The
      discriminatory immunostaining pattern associated with the 'MCW Melanoma Cocktail'
      (mixture of Melan- A, MART- 1, and tyrosinase) facilitated the feasibility of
      intraoperative evaluation of imprint smears of SLNs for melanoma metastases.
      METHODS: Imprint smears of 51 lymph nodes from 25 cases (48 SLNs and 3 non-SLNs,
      1 to 4 SLNs/case) of cutaneous melanoma were evaluated. RESULTS: Sixteen percent,
      8/51 lymph nodes (28%, 7/25 cases) were positive for melanoma metastases in
      immunostained permanent sections with the 'MCW melanoma cocktail'. All of these
      melanoma metastases, except 1 SLN from 1 case, were also detected in rapidly
      immunostained wet-fixed and air-dried smears (rehydrated in saline and postfixed
      in alcoholic formalin). The cytomorphology was superior in air-dried smears,
      which were rehydrated in saline and postfixed in alcoholic formalin. Wet-fixed
      smears frequently showed air-drying artifacts, which lead to the focal loss of
      immunostaining. None of the 5 SLNs from 5 cases exhibiting capsular nevi showed a
      false positive result with immunostained imprint smears. CONCLUSIONS: Melanoma
      metastases can be detected intraoperatively in both air-dried smears and wet
      fixed smears immunostained with the MCW Melanoma cocktail. Air-dried smears
      rehydrated in saline and postfixed in alcoholic formalin provide superior results
      and many practical benefits.

PMID- 15500703
TI  - The big problem of the missing cytology slides.
AB  - Cytology slides are often unique and irreplaceable. Unlike surgical pathology
      cases, where additional paraffin sections can be cut, cytology slides often
      cannot be duplicated because there are only a few direct smears or the diagnostic
      material is present on a single slide. Cytology slides are often "sent out" to
      other physicians, laboratories or hospitals, typically so that the pathologist at
      the institution where the patient will receive treatment can review the slides.
      Less often, a cytology lab sends out the slides for a second opinion or as part
      of the discovery process in a lawsuit, where they may or may not be defendants.
      Rarely, unique and irreplaceable cytology slides are lost. This article presents
      a hypothetical scenario that is based on reported state appellate court
      decisions. The article discusses some of the legal issues that will affect the
      defendant cytologist/cytology lab and the "expert cytologist," and suggests some
      steps a cytologist/cytology lab can take to minimize the risk of repercussions
      from a lost unique and irreplaceable cytology slide.

PMID- 15500706
TI  - [Approach to the research of human functional genomics in China].

PMID- 15500705
TI  - Signal transduction abnormalities in melancholic depression.
AB  - Intracellular signal transduction cascades, particularly those linked to protein
      kinases A (PKA) and C (PKC), have been implicated in mood disorders. This study
      examined the activity of PKA and PKC, as well as levels of PKA regulatory (R) and
      catalytic (C) subunit proteins, in fibroblasts cultured from skin biopsies from
      patients with major depression, melancholic subtype, in contrast to non
      melancholic depressives and controls (n = 12 each group). PKA activity was
      determined as a function of the transfer of 32P to a target polypeptide,
      Kemptide. R and C subunit expression was assayed in the melancholic depressed and
      normal control groups by Western blots. In a separate experiment, the degree of
      phosphorylation of the endogenous substrate cAMP response element-binding protein
      (CREB) was estimated in samples from melancholic and non-melancholic patients and
      normal controls (n = 8 each) after incubation with isoproterenol or phorbol
      ester, which activate PKA and PKC respectively. Melancholics had significantly
      reduced phosphorylation of Kemptide in contrast to non-melancholics and controls.
      This was associated with lower levels of PKA RII alpha, C alpha, and C beta
      subunit isoform proteins, but not RI alpha, RI beta, or RII beta. Furthermore,
      activation of both PKA and PKC was associated with reduced CREB-P in melancholics
      relative to normal controls. Finally, PKA activity was found to correlate
      positively with Hamilton depression scores after 16 weeks of treatment with
      serotonin reuptake inhibitor antidepressants. These data further implicate signal
      transduction abnormalities in melancholic major depression, particularly PKA and
      PKC. This suggests an abnormality of factors controlling the expression or
      degradation of these enzymes.

PMID- 15500707
TI  - [The value of treatment of liver transplantation for unresectable hepatocellular
      carcinoma].

PMID- 15500708
TI  - [Inhibitory effects of siRNA targeting epidermal growth factor receptor on
      proliferation and invasion of human glioblastoma cells].
AB  - OBJECTIVE: To study the inhibitory effects of siRNA targeting epidermal growth
      factor receptor (EGFR) on the proliferation and invasion of human glioblastoma
      cells. METHOD: Two siRNA expression constructs using psiRNA-NeoG2 vector, that
      targeted sequences of human EGFR receptor L domain (516 - 536) and catalytic
      domain (2400 - 2420) respectively, were constructed. Human malignant glioma cells
      of the line TJ905 were cultured in vitro and transfected with pcDNA3-hEGFR, anti
      sense RNA, blank vector psiRNA-NeoG2 (as negative control), psiRNA-NeoG2-516, and
      psiRNA-NeoG2-2400 respectively mediated by LipofectAMINE. Immunofluorescence
      assay and Western blotting were used to detect the EGFR expression. Cell
      apoptosis was detected by apoptotic index (AI) using TUNEL method. Cell cycle was
      analyzed by flow cytometry, and cell proliferative activities were measured by
      MTT. The expression and enzymatic activities of matrix metalloproteinase 9 (MMP
      9) were measured by Western blotting and gelatin zymography, and cell invasive
      capabilities were evaluated by Transwell-ECM method. RESULT: Immunofluorescence
      assay and Western blotting showed that the expression of EGFR was down-regulated
      by 90% and 92% respectively in the siRNA constructs transfected groups, while
      down-regulated by 82% in the antisense EGFR RNA transfected cells in comparison
      with the TJ905 cells and the cells transfected with blank vector. TUNEL assay
      showed that almost no apoptotic cell was found in the parental cells or the cells
      transfected with blank vector, however, apoptosis was increased in antisense EGFR
      transfected cells (AI = 7.2) and siRNA constructs transfected cells (AI = 13.7
      and 14.7; chi(2) = 31.549, P < 0.001). Flow cytometric analysis showed that the S
      phase fraction (SPF) was lowered in both siRNA constructs transfected cells than
      that in the parental cells, the cells transfected with blank vector, and the
      antisense EGFR transfected cells. MTT assay indicated that compared to the
      parental cells and the cells transfected with blank vector, the survival rates of
      transfected cells dramatically dropped down from the first day after implantation
      (P < 0.05), the siRNA transfected cells demonstrated much lower survival rate
      than the antisense EGFR transfected cells. Meanwhile, the expression and
      enzymatic activities of MMP-9 decreased significantly after the transfection of
      antisense EGFR into the TJ905 cells compared to the TJ905 cells and the cells
      transfected with blank vector, and were much lower in the siRNA groups than that
      in the antisense groups (P < 0.05). Cell invasive capability assay demonstrated
      the similar inhibitory results in the Transwell ECM-Matrigel study. CONCLUSION:
      Compared with antisense approach, siRNA expression constructs targeting EGFR
      specifically suppresses the EGFR expression, induces gene silencing, and inhibits
      cell growth and invasion. The plasmid-based siRNA approach should be a new
      strategy in glioma gene therapy targeting EGFR.

PMID- 15500710
TI  - [Gene screening of dermal papilla cells in the state of aggregative growth and
      full-length cloning of HSPC016 gene for bioinformatics].
AB  - OBJECTIVE: To screen the genes of dermal papilla cells (DPC) related to the
      property of aggregative growth, and clone the full-length cDNA of differential
      HSPC016 gene for functional analysis. METHODS: DPC were collected from the hair
      of an individual aged 18 approximately 30 6 hours after the death. The complete
      papillae of hair were isolated and then cultured. The total DNA was extracted.
      Suppression subtractive hybridization-polymerase chain reaction was employed to
      screen out the genes differentially expressed in the DPC under the state of
      aggregative growth pattern in vitro. Then, rapid amplification of cDNA ends
      (RACE) technique was used to amplify the full-length cDNA of HSPC016 in the DPC,
      and bioinformatic methods were used to analyze their possible function. RESULTS:
      A subtractive library of human DPC was set up, and some up-regulated and down
      regulated genes in the DPCs were screened out successfully. HSPC016 was
      identified to be a gene of 400 bp cDNA. Bioinformatic analyses and databases
      searching on the Internet indicated that this gene was mapped on chromosome 3
      q21.31 and included an open reading frame with 195 bp coding for an expected 64aa
      soluble protein. The putative protein belonged to PD053992 family and was
      homologous to T2FA gene in domain. CONCLUSION: The establishment of subtractive
      library of DPC provides a solid foundation for further screening the genes
      related to aggregative growth and analyzing their regulatory mechanisms in DPC.
      Further more, HSPC016 in DPC may act as a subunit of a functional complex and
      play a role on transcriptional regulation within nucleus.

PMID- 15500709
TI  - [The expression profiles of human chromosome 21 orthologues in mouse M II
      oocyte].
AB  - OBJECTIVE: To analyse the expression profile of orthologues of human chromosome
      21 (HC21) in mouse M II oocytes, and to discuss the relationship between this
      expression profile and early embryonic development and further to find the
      possible reasons of DS phenotypes genesis. METHODS: cDNA array and Global RT-PCR
      methods were used to analyse and identify the expression profile of 93 HC21
      orthologues in mouse M II oocytes. RESULTS: 26 of 93 orthologues were proved to
      be expressed in mouse M II oocytes and these genes were involved in many
      biological procedure including transcriptional, metabolism, ionic channel, and
      ubiquitin pathway etc. CONCLUSION: To our knowledge, this is first report about
      the HC21 orthologues expression profile in M II oocytes and this expression
      profile indicates that 26 of 93 HC21 orthologues may directly play important role
      in early development, and the biological information obtained from this
      experiment would be beneficial to understand imbalance of HC21 genes expression
      and the molecular mechanism of DS phenotypes genesis.

PMID- 15500711
TI  - [Diagnostic significance and clinical application of specific chimeric genes in
      soft tissue sarcomas by RT-PCR using paraffin-embedded tissues: a study of 103
      specimens].
AB  - OBJECTIVE: To investigate the expression of the chimeric genes resulting from the
      specific chromosomal translocations in soft tissue sarcomas (STS) and its
      diagnostic significance for STS. METHODS: The variety of fusion transcripts were
      detected in 103 cases of STS, including 30 cases of synovial sarcoma (SS), 15
      cases of rhabdomyosarcoma (RMS), 25 cases of Ewing's sarcoma/peripheral primitive
      neuroectodermal tumors (ES/pPNET), 12 cases of dermatofibrosarcoma protuberans
      (DFSP), 14 cases of aveolar soft part sarcoma (ASPS), 3 cases of leiomyosarcoma
      (LMS), 2 cases of malignant fibrous histocytoma (MFH), and 2 cases of
      fibrosarcoma (FS); and 20 cases of control tumors by reverse transcription
      polymerase chain reaction (RT-PCR) using formalin fixed, paraffin embedded
      specimens. RESULTS: Of the 34 cases of SS 28 (93.3%) expressed SSX-SYT chimeric
      transcripts (14 were positive for SYT-SSX1, 9 for SYT-SSX2). Four of the six
      cases of alveolar RMS had a PAX3/PAX7-FKHR fusion transcript. None of the 9 cases
      of embryonic and polymorphic RMS expressed PAX3/PAX7-FKHR. Of the 25 cases of
      ES/pPNET, 19 were positive for EWS-FLI1 fusion transcript and 1 for EWS-ERG
      fusion transcript. COL1A1-PDGFB fusion transcript was expressed in 8 of the 12
      cases (66.7%) of DFSP. Of the fourteen cases of ASPS, ten expressed ASPL-TFE3
      fusion transcript. None of the 3 cases of LMS, 2 cases of MFH, 2 cases of FS, and
      20 control cases contained any of the fusion transcript. CONCLUSION: Chimeric
      gene transcript resulting from specific chromosomal translocations is a reliable
      index for the molecular diagnosis of STS and RT-PCR assay for detection of
      specific fusion gene provides a useful tool for confirmation of the diagnosis of
      STS in diagnostically difficult cases and in retrospective studies.

PMID- 15500712
TI  - [Wild-type Smad3 gene promotes osteoblastic differentiation of rat bone marrow
      derived mesenchymal stem cells in vitro].
AB  - OBJECTIVE: To observe the effect and mechanism of wild-type Smad3 gene on the
      proliferation and osteoblastic differentiation of rat bone marrow-derived
      mesenchymal stem cell (MSC). METHODS: Rat bone-derived MSC were cultured and
      transfected with the complexes of pcDNA3.0-Myc-Smad3 or pcDNA3.0-Myc-Smad3DeltaC
      and LipofectAMINE reagent. Immunofluorescence technique was performed to evaluate
      the c-Myc expression. The cell proliferation was detected by MTT method. In order
      to observe the osteoblastic characteristics in stable expression MSC, alkaline
      phosphatase (ALP) mRNA and core binding factor alpha1 (cbfa1) mRNA were
      investigated by RT-PCR technique, and ALP activity and mineralization were
      examined by PNP method and alizarin red staining respectively. PD98059 was used
      to interdict selectively ERK pathway in order to investigate the effect of ERK
      pathway on Smad3 regulating MSC. RESULTS: c-Myc protein was expressed in Smad3
      MSC and Smad3DeltaC-MSC. The proliferation of Smad3-MSC was slower than that of
      Smad3DeltaC-MSC or V-MSC. The relative levels of ALP mRNA and cbfa1 mRNA in Smad3
      MSC were higher markedly than those in Smad3DeltaC-MSC or V-MSC, as well as ALP
      activity and mineralization. However, without a significant difference ALP
      activity and mineralization was after PD98059 treatment (both slightly decreased
      P > 0.05). CONCLUSION: The wild-type Smad3 gene, which is a crucial component
      promoting bone formation, can inhibit the proliferation of MSC and promote the
      osteoblastic differentiation and maturation of MSC independent of ERK pathway.

PMID- 15500713
TI  - [Gene therapy of tyrosine hydroxylase, aromatic L-amino acid decarboxylase, and
      GTP cyclohydrolase genes in rat model of Parkinson's disease].
AB  - OBJECTIVE: To detect the expression and function of enzyme genes involved in
      biosynthetic pathway for dopamine in vitro and assess their effect in rat model
      of Parkinson's disease. METHODS: Cos7 cells were transfected with separate adeno
      associated virus (AAV) expressing tyrosine hydroxylase (TH) gene, aromatic L
      amino acid decarboxylase (AADC) gene and GTP cyclohydrolase I (GCH-I) gene. The
      expression and function of the three genes were detected by methods of
      immunohistochemistry, in situ hybridization and high performance liquid
      chromatograph and electrochemical detection (HPLC-ECD). Gene engineered cells
      were sequentially transplanted into the striatum of 6-hydroxy-dopamine-leisioned
      Parkinsonian rat by stereotaxic instrastriatal injection. The asymmetric
      rotations of these rats after apomorphine administration were detected every week
      after transplantation. 10 weeks after grafting, the animals were sacrificed and
      the dopamine produced in the striatum was detected by HPLC-ECD. RESULTS: In vitro
      experiments showed that the three genes were high expressed in Cos7 cells. When
      Cos7 cells expressing TH, AADC and GCH-I were cocultured, they produced large
      amount of dopamine in the condition of existance of L-tyrosine. Furthermore,
      triple genes therapy resulted in greater dopamine production in the striatum of
      Parkinsonian rats and improved the rotational behavior of the rats more
      efficiently than did single gene therapy. However, the production of dopamine in
      the rats with triple genes therapy is no more than double genes therapy.
      CONCLUSION: For gene therapy in Parkinson's disease, the amount of target genes
      to be used should be determined by the level of doperminergic neurons damaged. In
      the present study, the efficiency of multiple genes therapy is significantly
      better than that of single gene therapy.

PMID- 15500714
TI  - [Effective evaluation of liver transplantation for hepatocellular carcinoma].
AB  - OBJECTIVE: To evaluate the effect of liver transplantation for hepatocellular
      carcinoma and to explore the suitable indication for liver transplantation for
      advanced primary hepatocellular carcinoma. METHOD: Clinical data were collected
      and studied with 43 patients with cirrhosis who had unresectable hepatocellular
      carcinoma and who underwent liver transplantation from August, 2000 to December,
      2003. All the survived patients were followed up. RESULTS: The longest following
      period was 45 months. 18 patients died by the end of the April, 2004. The 1-year
      survival rate was 85.5%, the 2-year survival rate 65.5%, the 3-year survival rate
      was 43.0%. CONCLUSION: In our country, some advanced primary hepatocellular
      carcinoma without extrahepatic metastasis is still indicated for liver
      transplantation. Some patients could have the opportunity to survive relatively
      long time.

PMID- 15500715
TI  - [Diagnosis and treatment of hepatic artery thrombosis after liver
      transplantation].
AB  - OBJECTIVE: To summarize the experience in prevention, diagnosis, and management
      of hepatic artery thrombosis (HAT) after orthotopic liver transplantation (OLT).
      METHODS: The clinical data of 198 patients undergoing OLT from April 1993 to
      September 2003 were analyzed among which 96 underwent anastomosis of hepatic
      artery with 7/0 prolene by running suture (group 1) and 102 by intermittent
      suture (group 2). Ultrasonic examination was routinely performed every day within
      two weeks after operation and then performed selectively afterwards. RESULTS: The
      incidence rate of HAT in group 2 was 1.0% (1/102), significantly lower than that
      in group 1 (6.3%, 6/96) (chi(2) = 4.027, P = 0.045). HAT was discovered by color
      ultrasonography in 6 of the 7 cases, and by exploratory laparotomy in 1 case. Out
      of the 7 patients with HAT, 6 received emergency thrombectomy, and 1 received
      conservative therapy but died from tumor recurrence eventually. Biliary
      complication developed in 3 out of the 6 cases after thrombectomy of whom 2 died
      of liver failure and one waited for retransplantation. One of the other 3 cases
      died of renal failure, and 2 cases survived. The mortality of patients with HAT
      was 57.1% (4/7). CONCLUSION: The technique of hepatic artery anastomosis is the
      key factor for the prevention of HAT. Routine ultrasonography is important in
      early detection of HAT after OLT. Biliary complication is a severe outcome
      secondary to HAT.

PMID- 15500716
TI  - [Identification of FIP1L1-PDGFRA fusion, and expression of signal transducer and
      activator of transcription 5 in hypereosinophilic syndrome].
AB  - OBJECTIVE: To determine whether FIP1L1-PDGFRA fusion exists in hypereosinophilic
      syndrome (HES) patients, explore the relationship between FIP1L1-PDGFRA fusion
      and clinical phenotypes, and observe and reveal the expression of signal
      transducer and activator of transcription 5 (STAT(5)) in granulocytes of HES and
      the biological significance thereof. METHODS: Specimens of peripheral blood were
      collected from 4 HES patients diagnosed based on the criteria of Chusid et al.
      Total RNA was extracted from granulocytes and cDNA was synthesized by reverse
      transcription. Nested-PCR was used to amplify the target fusion gene and the
      positive PCR fragments were sequenced directly. Total protein of the peripheral
      granulocytes was extracted. Western blotting was used to detect the expression of
      STAT(5) protein in the granulocyte lysates. RESULTS: FIP1L1-PDGFRA fusion genes
      were found in 3 of the 4 HES patients. The break points in PDGFRA were all
      located at exon 12, while in FIP1L1 the break points were highly variable,
      located at exon 8a, intron 8a, and exon 8 respectively. The patients with FIP1L1
      PDGFRA fusion were susceptible to cardiac involvement. The expression of STAT(5)
      protein was upregulated in FIP1L1-PDGFRA positive HES patients, while STAT(5)
      protein expression was negative in HES patients without FIP1L1-PDGFRA fusion.
      CONCLUSION: FIP1L1-PDGFRA fusion has a universal significance for HES. The
      identification of FIP1L1-PDGFRA rearrangement is a useful molecular mark for HES
      diagnosis and works as the therapeutic target of imatinib. Furthermore, the
      activation of STAT(5), a downstream signal of the FIP1L1-PDGFRA fusion, indicates
      that HES is a malignant clonal disease of the hematopoietic tissue.

PMID- 15500717
TI  - [A national survey on low vision and blindness of 0 - 6 years old children in
      China].
AB  - OBJECTIVE: To get the prevalence of visual impairment of children in China. The
      national survey of low vision and blindness of 0 approximately 6 years old
      children was conducted in China in 2001. METHOD: Stratified, random, cluster,
      systematic sampling was used to select 60 124 subjects from 360 clusters from 6
      provinces in China. The trained doctors examined every individual. RESULT: 64
      subjects were defined as visual impairment among the total 60 124 participated
      subjects in the survey. The total prevalence of visual impairment is 1.1 per
      thousand. The 20 subjects is blindness and the prevalence is 0.33 per thousand.
      44 subjects is low vision and the prevalence is 0.73 per thousand. The major
      causes of visual impairment are amblyopia (32.8%), retinal and optic nerve
      diseases (15.6%), congenital cataract (14.1%) and congenital glaucoma (6.3%).
      CONCLUSION: The prevalence of blindness is close the level of developed country.
      Amblyopia is the leading cause of all visual impairment. Most causes of visual
      impairment, amblyopia and congenital cataract are curable.

PMID- 15500718
TI  - [Finite element analysis of changes in femoral stresses after elite total hip
      arthroplasty].
AB  - OBJECTIVE: To determine the variation in femoral stress after insertion of Elite
      cemented femoral prosthesis. METHODS: Three-dimentional finite element models of
      the normal human femur and Elite femoral prosthesis were developed through CT
      scan. With the application of hip joint loading, quantitatively measure stress
      changes of an intact femur with corresponding femur inserted with Elite implants
      were measured. RESULTS: Compared with intact femur, insertion of Elite implants
      into the femoral canal decreased the proximal femoral stresses level, especially
      in calcar femoral, femur wall and tuberositas. However, the stress in the
      prosthesis distal end. CONCLUSION: Insertion of Elite implants induced
      significant stress shielding in the proximal femur, especially at calcar femoral,
      femur wall and tuberositas. However, stress concentrates in the prosthesis distal
      end.

PMID- 15500719
TI  - [Application of computer-assistant neuronavigation in spinal operation].
AB  - OBJECTIVE: To discuss the efficacy, accuracy, and safety of computer-assistant
      neuronavigation in operation of vertebrae and spinal cord. METHODS: The data of
      computer-assistant neuronavigation used in the operation for 41 cases, including
      9 cases of neurinoma, 10 cases of ependymoma, 5 cases of angioreticuloma, 7 cases
      of spinal meningioma, 4 cases of astrocytoma, and 1 case of cysticercosis, and 1
      case of osteoblastoma. from March 2001 to December 2003 were reviewed. RESULTS:
      Twenty-six screws were fixed in 4 patients. Total removal was succeeded in 33 of
      the 37 cases of 37 spinal tumors and all patients survived after operation.
      CONCLUSION: Image-guided navigation for spinal surgery is able to save time and
      reduce operational lesion. More importantly, it improves neurosurgeon's
      comprehension of spinal anatomy.

PMID- 15500720
TI  - [Effects of hemofiltration modifies during extracorporeal circulation in the
      surgery of pulmonary hypertension with congenital heart defects on endothelin
      level and the ratio of pulmonary pressure/systemic pressure ].

PMID- 15500721
TI  - [Endoscopic diagnosis and treatment of juvenile colonic polyps and its pathologic
      characteristics].

PMID- 15500722
TI  - [Preventive effect of anterior chamber associated immune deviation on endotoxin
      induced uveitis].
AB  - OBJECTIVE: To determine the effect of anterior chamber associated immune
      deviation (ACAID) on endotoxin-induced uveitis (EIU) and the possible mechanism.
      METHODS: ACAID animal model was induced by injection of 5 microl IRBP (10
      microg/microl) into the anterior chamber (AC) of Spar-Dawley (SD) rats. Then 200
      microg LPS was injected into hind footpads at different time points after AC
      inoculation. The animals were randomly divided into 3 groups: positive control
      (LPS injection only), 3 d group (LPS injection 3 days after IRBP inoculation), 7
      d group (LPS injection 7 days after IRBP inoculation). Delayed type
      hypersensitivity (DTH) was examined to determine the development of ACAID. Then
      the serum level of IL-10 was evaluated by ELISA, and GATA-3 expression at the
      different time points after IRBP injection was assayed by reverse transcription
      polymerase chain reaction (RT-PCR) and Western blot on mRNA and protein level
      respectively. The ocular inflammation was observed clinically; at the same time,
      the eye was extirpated and histological examination was performed. RESULTS: In
      control and 3 d groups, significant DTH reaction was induced, but the serum level
      of IL-10 could not be detected and GATA-3 expression was not increased. While in
      7 d group, the DTH reaction could not be induced, and IL-10 and GATA-3 expression
      increased significantly at both the mRNA and protein levels. The clinical
      manifestation was significantly alleviated in the 7 d group; Histological
      examination displayed that the inflammatory cells were significantly reduced in
      iris/ciliary body, anterior and posterior chambers, vitreous body and retina of
      the rats in 7 d group. CONCLUSION: The development of ACAID can reduce the ocular
      inflammation induced by LPS, that is related to the increase of GATA-3 and IL-10
      expression.

PMID- 15500723
TI  - [Preparation of mB7.1-GPI and SEA-TM dual-anchored tumor cell vaccine and its
      antitumor effect].
AB  - OBJECTIVE: To prepare the SEA-TM and mB7.1-GPI dual-anchored EL-4 cell vaccine
      and to investigate its antitumor effects. METHODS: mB7.1-GPI-anchored EL-4 cell
      vaccine, SEA-TM-anchored EL-4 cell vaccine, SEA-TM and mB7.1-GPI dual-anchored EL
      4 cell vaccine were prepared. In vitro the biological activities of these
      vaccines were measured using a lymphocyte proliferation assay and cytokine
      release assay on splenocytes derived from C57BL/6 mice. The splenocytes were co
      cultured with EL-4 or EL-4/mB7.1-GPI or EL-4/SEA-TM or EL-4/SEA-TM + mB7.1-GPI
      (treated with Mitomycin C). Lymphocyte proliferation was determined with MTT
      assay, the concentrations of cytokines (IL-2 and IFN-gamma) were measured using a
      ELISA technique. Forty C57BL/6 mice were inoculated with EL-4 cells, after 3 days
      the mice were randomly divided into 5 groups with 8 in each and were treated with
      PBS, EL-4 cell vaccine, EL-4/mB7.1-GPI cell vaccine, EL-4/SEA-TM cell vaccine and
      EL-4/SEA-TM + mB7.1-GPI cell vaccine respectively, vaccines were injected three
      time with two-day interval. Animals were observed daily, tumor sizes were
      measured every third day. Twenty-five days after tumor challenge, 3 mice in each
      group were sacrificed and splenic lymphocytes were isolated to examine the
      activity of natural killer cells (NK) and cytolytic T lymphocytes (CTL). The
      survival of the remaining 5 mice in each group was observed till the 90th day.
      RESULTS: mB7.1-GPI or/and TM-SEA fusion protein was stably anchored onto the
      surface of EL-4 tumor cells. EL-4/mB7.1-GPI or EL-4/SEA-TM had a stronger ability
      to stimulate lymphocyte proliferation and IL-2 and IFN-gamma production than EL-4
      (P < 0.05); while EL-4/SEA-TM + mB7.1-GPI showed a further increased ability than
      EL-4/mB7.1-GPI and EL-4/SEA-TM in stimulating lymphocyte proliferation and
      cytokine production in vitro (P < 0.05). Volume of tumor was smaller and survival
      time of mice was longer in EL-4/mB7.1-GPI vaccine group, EL-4/SEA-TM vaccine
      group and EL-4/SEA-TM + mB7.1-GPI vaccine group, comparing with PBS group and EL
      4 cell vaccine group (P < 0.05). Tumor volume was much smaller and survival time
      of mice was much longer in EL-4/mB7.1-GPI + mB7.1-GPI vaccine group, comparing
      with EL-4/SEA-TM vaccine group and EL-4/mB7.1-GPI vaccine group (P < 0.05).
      Lymphocytes derived from the mice treated with EL-4/SEA-TM + mB7.1-GPI showed
      much higher NK activity and CTL activity than those derived from EL-4/mB7.1-GPI
      vaccine group and EL-4/SEA-TM vaccine group (P < 0.05), meanwhile the NK activity
      and CTL activity of EL-4/mB7.1-GPI vaccine group and EL-4/SEA-TM vaccine group
      was higher than EL-4 vaccine group (P < 0.05). CONCLUSION: mB7.1-GPI or/and SEA
      TM fusion protein was stably anchored onto the surface of EL-4 tumor cells. The
      tumor cell vaccines prepared from these cells exhibited antitumor effect. The
      mB7.1-GPI and SEA-TM dual-anchored tumor cell vaccine had much stronger antitumor
      effect than the single-anchored tumor cell vaccine.

PMID- 15500724
TI  - [Diagnosis and treatment of mesenteric venous thrombosis].

PMID- 15500726
TI  - [Pay attention to using antibiotic not appropriate].

PMID- 15500727
TI  - [Progress in the study of stem cells differentiation into hepatocytes].

PMID- 15500728
TI  - [Gamma-locator apparatus in the assistance of location of parathyroid neoplasm in
      operation ].

PMID- 15500729
TI  - [Attention to perioperative treatment].

PMID- 15500730
TI  - [National congress on perioperative treatment of organ transplantation in 2004 in
      China].

PMID- 15500731
TI  - [Effect of astrgaloside IV on the long-term consequences of renal ischemia
      reperfusion injury in rat].
AB  - OBJECTIVE: To observe the effect of astrgaloside IV (Astr) on the long-term
      consequences of renal ischemia-reperfusion injury (IRI) in rat. METHODS: Fifty
      four male Sprague-Dawley rats were randomized into 3 equal groups: IRI group,
      Astr group, and sham operation group. All rats underwent right nephrectomy and
      isolation of the left renal artery. The left renal arteries of the IRI group and
      Astr group were gripped by vascular clamp for 60 minutes and that of the sham
      operation group was only isolated without gripping. Two milliliters of Astr
      solution (0.1 g/L) was perfused into the stomach of the rats in the Astr group
      three days before and after the operation respectively. The rats in the IRI and
      sham operation groups were perfused with normal saline of the same volume. Four,
      twelve, and twenty-four weeks after the operation 24-hour urine specimens of the
      rats were collected to detect the urine protein. At each time point 6 rats from
      each group were anesthetized and blood was collected from the abdominal aorta to
      measure the level of serum creatinine (Cr), their left kidneys were taken out to
      undergo pathological examination and extraction of mRNA. Histochemistry was used
      to detect the expression of tumor growth factor (TGF)-beta1 protein in the renal
      tissues. RT-PCR was used to detect the expression of TGF-beta1 mRNA. Collagen
      staining and immunohistochemistry were used to measure the proportion of collagen
      positive material to the total area. RESULTS: The level of urine protein was
      increased progressively, those 12 and 24 weeks after the operation in the IRI
      group were significantly higher than those in the Astr and sham operation groups
      (all P < 0.05). The serum Cr 4 weeks after the operation was 36 micromol/L +/- 4
      micromol/L, significantly higher than those in the Astr and sham operation groups
      (31 micromol/L +/- 8 micromol/L and 31 micromol/L +/- 5 micromol/L), and the
      serum Cr levels 4 weeks 12 and 24 weeks after the operation in the IRI group
      remained significantly higher than those in the Astr and sham operation groups
      (all P < 0.05). Collagen staining showed that the glomerular basement membrane,
      tunica adventitia vasorum, and adventitia of renal tubule were remarkably redder
      in the IRI than in the Astr and sham operation groups. The expression of TGF
      beta1 protein was progressively increased since 12 weeks after the operation in
      the IRI group, significantly stronger in the Astr and sham operation groups. The
      expression of TGF-beta1 mRNA was progressively increased since 12 weeks after the
      operation in the IRI and Astr groups, significantly stronger than that in the
      sham operation group (P < 0.05). However, the expression of TGF-beta1 mRNA 24
      weeks after the operation was significantly stronger in the IRI group than in the
      Astr group (P < 0.05). CONCLUSION: After renal IRI the probability of development
      of renal fibrosis increases. Astrgaloside IV markedly ameliorates renal injury by
      downregulating the TGF-beta1 expression.

PMID- 15500732
TI  - [Modified low-potassium dextran solution in advantage of perfusion for lung
      preservation].

PMID- 15500733
TI  - [Histopathological changes of urinary bladder after transplantation of buccal
      mucosa and colon mucosa in dog].

PMID- 15500734
TI  - [Relationship between ATP-binding cassette transporter 1 R219K genetic variation
      and blood lipids].
AB  - OBJECTIVE: To investigate whether ATP-binding cassette transporter 1 (ABCA1)
      R219K genetic variation is correlated with blood lipids. METHOD: Specimens of
      peripheral blood were collected from 692 patients with cerebral apoplexy, aged 62
      +/- aged 12, and 352 sex- and age-matched persons without cardio-cerebro-vascular
      disease. Polymerase chain reaction-restricted fragments length polymorphism (PCR
      RFLP) was used to determine the ABCA1 genotype: RR type (177 bp), RK type (177
      bp, 107 bp, and 70 bp); and KK type (107 bp and 70 bp). The RR and KK type
      products were sequenced. RESULTS: The level of HDL-C showed an upward trend in
      the sequence of RR, RK, and KK genotypes with a significant difference between RR
      genotype (1.3 mmol/L +/- 0.4 mmol/L) and KK genotype (1.4 mmol/L +/- 0.4 mmol/L),
      especially in the males. The levels of TG tended downward in the sequence of RR,
      RK, and KK genotypes, however, without a significant difference between any 2
      genotypes. Linear regression analysis showed that the HDL-C level was positively
      correlated with age in the noncarriers of ABCA1R219K genetic variation (RR
      genotype), and the TC level was negatively correlated with age in the carriers
      (RK + KK genotype). In the cohort aged </= 70 the HDL-C level was higher in
      carriers than in noncarriers. CONCLUSION: ABCA1R219K genetic variation results in
      a beneficial profile of blood lipids, more evident in males. RK + KK genotype is
      more pronounced in the individuals aged </= 70.

PMID- 15500735
TI  - [FCGR3B gene frequencies and FCGR3 gene variants in Chinese: a study in 487
      Chinese individuals from Zhejiang Province].
AB  - OBJECTIVE: To investigate the FCGR3B gene frequencies and FCGR3 variants in a
      Chinese population from Zhejiang Province. METHODS: DNA was extracted from the
      blood specimens of 487 healthy blood donors from Zhejiang Province. The FCGR3B
      gene frequencies were determined by polymerase chain reaction with sequence
      specific primers (PCR-SSP). The 19 specimens with 3 different FCGR3B genotypes
      underwent FCGR3 gene cloning and sequencing. RESULTS: The gene frequencies of
      FCGR3B(*1), FCGR3B(*2), and FCGR3B(*3) in these 487 individuals were 0.564,
      0.429, and 0.000 respectively. The genotype frequency of FCGR3B(null) was 0.62%
      (3/487). Sequencing of FCGR3 revealed that in 7 out of the 19 Chinese individuals
      variants caused by single nucleotide exchanges at one or more of the polymorphic
      positions 141, 147, 227, 266 and 277 in exon 3 also existed in this Chinese
      population. CONCLUSION: FCGR3B(*1) gene is more frequent in a Chinese population
      from Zhejiang Province than the FCGR3B(*2) gene, and the FCGR3B(*3) gene seems to
      be absent. Gene variants caused by single nucleotide exchanges are found in
      addition to the well known forms, but the reason for this remains unclear.

PMID- 15500736
TI  - [Strategy for the treatment of intractable aneurysms].
AB  - OBJECTIVE: To summarize the treatment of various intractable aneurysms and
      analyze the results. METHODS: A retro-respective review was made to the clinical
      data of 24 patients, 20 males and 4 females, aged 15 approximately 71 with an
      average age of 45.8, with intractable aneurysms, caused by arteriosclerosis in 13
      cases, by trauma in 8 cases, and by vascular deformity. RESULTS: The 24 patients
      were diagnosed as intractable aneurysms by color Doppler ultrasonic examination
      or digital subtraction angiography. They all underwent different operations with
      a general mortality of 8.39%. CONCLUSION: Enough preoperative evaluation based on
      the size, location, relation with nearby organs and systematic complications. for
      different intractable aneurysm is necessary. Incision design and operation method
      are important for the treatment.

PMID- 15500737
TI  - [Relationship between expression of thymidylate synthase and colorectal
      carcinoma].
AB  - OBJECTIVE: To study the relationship between the expression of thymidylate
      synthase (TS) gene and the prognosis of colorectal carcinoma and between the TS
      expression and the effect of 5-fluorouracil (5-Fu) on advanced colorectal
      carcinoma. METHODS: 134 formalin-fixed and paraffin-embedded specimens of
      colorectal carcinoma obtained during operation from 134 patients, 65 males and 69
      females, aged 34 approximately 76 with an average age of 51 +/- 11, 16 with
      differentiated carcinoma and 118 with undifferentiated carcinoma, 4 with
      infiltration into mucous layer, 21 into submucous layer, 100 into muscular layer,
      and 5 into serous layer, 25 without lymphatic metastasis and 109 with lymphatic
      metastasis, 4 in stage IB, 15 in stage II, 90 in stage IIIA, and 27 in stage IIIB
      by Dukes staging, underwent immunohistochemistry (ABC methods) to determine the
      expression of TS. After operation all patients received chemotherapy with
      leucovorin and 5-Fu for 4 approximately 6 periods and were followed up for 9
      approximately 72 months. RESULTS: Eighty-two specimens showed high TS expression
      and 52 showed low TS expression. The grade of TS expression was significantly
      correlated with four clinicopathologic variables: histological type, depth of
      invasion, lymphatic metastasis, and Dukes' stage (all P < 0.001). The 5-year
      survival rate for the low TS group was 57.69%, significantly lower than that of
      the high TS group (21.95%, P < 0.001). Multivariate analysis revealed that three
      variables (histological type, depth of infiltration, and TS grade) independently
      contributed to the survival rate (all P < 0.05), especially the TS grade (all P <
      0.0001). The relative hazard ratio of TS grade was 1.241. CONCLUSION: The
      expression of TS is one of the important prognosis indicators of colorectal
      carcinoma. It is also a relatively reliable indicator of whether 5-Fu should be
      used in the treatment of patients with colorectal carcinoma.

PMID- 15500738
TI  - [Significance of serum anti-Clq Ab in evaluation of lupus nephritis activity and
      its curative effects of pharmacotherapy on lupus nephritis].
AB  - OBJECTIVE: To investigate the significance of serum anti-C1q Ab of evaluation of
      lupus nephritis activity and its curative effects of cyclophophamide therapy on
      lupus nephritis (LN). METHODS: The level of serum anti-C1q antibody of 75
      patients with LN was examined by enzyme-linked immunosorbent assay (ELISA) of the
      75 patients the incipient cases had never received corticosteroid and
      immunosuppressant and the recurrent cases had stopped the immunosuppressant
      treatment for more than 3 months and were treated, if so, with prednisone with
      the dosage </= 10 mg/d. Thirty-one patients underwent renal biopsy. The patients
      underwent treatment of cyclophophamide. The relationships between serum anti-C1q
      Ab level and lupus nephritis activity, renal pathohistology, as well as
      laboratory parameters were analyzed, followed by further regular follow-up to
      investigate its influence to the curative effect. RESULTS: Fifty-five of the 75
      patients (73.3%) were anti-C1q Ab positive with the level of (92 U/ml +/- 41
      U/ml). The mean time of conversion of urinary protein into negative was 9 months
      in the positive C1q positive group and 6 months in the C1q negative group. One
      year after, 25% of those with positive C1q antibody failed to convert into
      urinary protein negative, and 90% of those with negative C1q antibody converted
      into urinary protein negative. One year after, 32% of those whose serum C1q
      antibody remained positive 1 month after the treatment failed to convert into
      urinary protein negative, and 91% of those whose serum C1q antibody remained
      positive 1 month after the treatment converted into urinary protein negative. The
      serum anti-C1q Ab level was positively correlated with the lupus nephritis
      clinical active index, proteinuria, and titer of anti-dsDNA, and was negatively
      correlated with the levels of serum C3 and C4. Renal biopsies showed a positive
      correlation between the serum anti-C1q Ab level and the activity index of renal
      pathohistology. Multivariate analysis showed that the serum anti-C1q Ab level
      after treatment were associated with the curative effect and prognosis of LN.
      CONCLUSION: Serum anti-C1q Ab is not only a good index of lupus nephritis
      activity, but also reflects renal involvement and curative effect. That serial
      measurement of serum anti-C1q Ab may provide better clinical strategies for the
      therapy.

PMID- 15500739
TI  - [The evolvement of Th1/Th2 imbalance accommodates to the progress of airway
      inflammation in asthmatic subjects and rat model].
AB  - OBJECTIVE: To observe the production of IFN-gamma and IL-4 released in peripheral
      T lymphocytes in asthmatic patients and rat models and to clarify the dynamic
      changes of proliferation and differentiation of T lymphocytes during the progress
      of airway inflammation. METHODS: Twenty patients with moderate to severe acute
      exacerbation and 15 patients with remission of asthma were included in this
      study. Ten normal volunteers were also enrolled as control group. T lymphocytes
      were obtained from their peripheral blood and the percentage of IFN
      gamma(+)CD4(++), IFN-gamma + CD8(++) and IL-4(+)CD4(++) cells were determined by
      flow cytometric method. Asthmatic rat models were established by sensitizing and
      challenging by ovalbumin (OVA), and the blood samples were taken and the
      percentage of IFN-gamma(+)CD4(+), IFN-gamma + CD8(+) and IL-4 + CD4(+) cells were
      assessed 2, 4, 6, 8, 10, 12, 24, 48, and 72 h after OVA challenge. RESULTS: (1)
      The percentages of IFN-gamma(+)CD4(+), IFN-gamma(+)CD8(+) and IL-4(+)CD4(+) cells
      in the peripheral blood were significantly higher in the patients with acute
      exacerbation [(30% +/- 10%), (42% +/- 15%), and (4.2% +/- 1.6%) respectively]
      than those in the patients with remission asthma [(20% +/- 8%), (30% +/- 10%),
      and (2.0% +/- 0.8%) respectively, and P < 0.001;] and those in the normal
      subjects [(18% +/- 8%), and (24% +/- 9%), P < 0.01, and (1.9% +/- 0.9%), P <
      0.001; respectively]. But all the parameters were not different significantly
      between the patients with remission asthma and the normal subjects. (2) In the
      asthmatic rat models, the IFN-gamma(+)CD4(+) cells in peripheral blood increased
      2 h after OVA challenge (5.7% +/- 1.6%), and peaked 10 h after (9.9% +/- 4.4%),
      and decreased afterwards. The IFN-gamma(+)CD8(+) cells in peripheral blood
      increased 2 h after (11.5% +/- 5.1%) OVA challenge, and peaked 10 h after (38.7%
      +/- 6.3%), and then decreased afterwards. The IL-4(+)CD4(+) cells increased 2 h
      (1.7% +/- 1.0%) after OVA challenge, and peaked 36 h after (4.0% +/- 1.6%), and
      then decreased. CONCLUSION: Both Th1 (IFN-gamma) and Th2 (IL-4) cytokines
      generated by peripheral blood mononuclear cells in asthma subjects and asthmatic
      rat models play a role in the development of airway inflammation in bronchial
      asthma dynamically. Th1 cytokines dominate at the early stage of airway
      inflammation, whereas Th2 cytokines achieves the major effects at later stage of
      the inflammation. It suggests that using different strategy in treatment of
      asthmatics in early stage and late stage may be necessary to control asthma.

PMID- 15500740
TI  - [Relation between intra-uterine cytomegalovirus infection and pregnancy outcome].

PMID- 15500742
TI  - [Etiology and clinical characteristics of congenital nephrogenic diabetes
      insipidus].

PMID- 15500743
TI  - [Diagnosis and treatment of extramammary Paget's disease].

PMID- 15500745
TI  - [Identification and expression of blaCTX-M-14 and blaCTX-M-24].
AB  - OBJECTIVE: To identify the ESBL gene and the prevalence in Escherichia coli and
      Klebsiella pneumoniae strain isolated from Huashan Hospital, Shanghai. METHODS:
      Isolates were confirmed as an ESBL producing strain by double-disk synergy test
      and NCCLS Confirmatory Test. Antibiotic susceptibilities were determined by
      standard agar dilution procedure on Mueller-Hinton agar. To determine whether the
      resistance was transferable, the conjugation experiment was performed; plasmids
      were isolated from clinical isolates and transcojugants. The partial bla(gene) of
      ESBL producing isolates and their transcojugants were detected by PCR using
      universal primers for TEM, SHV, CTX-M-1group, Toho-1group, CTX-M-13group
      respectively. The entire bla(CTX-M-13) group were amplified by PCR using the
      primers outside the Open Reading Frame (ORF) of CTX-M-13group beta-lactamases;
      the PCR products of entire bla(CTX-M-13)group were cloned into vector and the
      recombinant plasmids were transformed into the recipient strain for expression;
      the PCR products were also directly sequenced and analyzed; the clinical isolates
      of ESBL producers were detected by PFGE. RESULTS: ESBL producers were resistant
      to most beta-lactams and non-beta-lactams. Most transconjugants were obtained at
      frequency of 10(-4) approximately 10(-5) and resistance to non-beta-lactams was
      cotransferred with the ESBL activity to the transconjugant. A plasmid of about >
      23.1 kb was obtained from each tansconjugant by plasmid extraction. Partial gene
      amplification products of CTX-M-13 group gene were obtained from isolates and
      their transconjugants. The bla(CTX-M-13)group from 4 transconjugants were
      identified as bla(CTX-M-14), and other six were bla(CTX-M-24); those ESBLs were
      mediated by plasmids (> 23.1 kb); the transformants producing CTX-M-14 or CTX-M
      24 were resistant to most beta-lactams, which were much more resistant to
      cefotaxime than to ceftazidine; PFGE patterns of those isolates were different.
      CONCLUSION: clinical isolate of Escherichia coli and Klebsiella pneumoniae
      isolated from Huashan Hospital, Shanhai produced CTX-M-14 or CTX-M-24, which
      caused the isolate resistant to most beta-lactams; no clone spread in those
      isolates was found.

PMID- 15500746
TI  - [Study on the interface of human hepatocyte/micropore polypropylene
      ultrafiltration membrane].
AB  - OBJECTIVE: To found a new interface of human hepatocyte/micropore polypropylene
      ultrafiltration membrane (MPP) with good cytocompatibility so as to construct
      bioartificial bioreactor with polypropylene hollow fibers in future. METHODS: MPP
      ultrafiltration membrane underwent chemical grafting modification through
      ultraviolet irradiation and Fe(2+) reduction. The contact angles of MPP and the
      modified MPP membranes were measured. Human hepatic cells L-02 were cultured. MPP
      and modified MPP membranes were spread on the wells of culture plate and human
      hepatic cells and cytodex 3 were inoculated on them. Different kinds of
      microscopy were used to observe the morphology of these cells. RESULTS: The water
      contact angle of MPP and the modified MPP membranes decreased from 78 degrees +/-
      5 degrees to 27 degrees +/- 4 degrees (P < 0.05), which indicated that the
      hydrophilicity of the membrane was improved obviously after the grafting
      modification. Human hepatocyte L-02 did not adhere to and spread on the modified
      MPP membrane surface, and only grew on the microcarrier cytodex 3 with higher
      density and higher proliferation ratio measured by MTT. CONCLUSION: Grafting
      modification of acrylamide on MPP membrane is a good method to improve the human
      hepatocyte cytocompatibility with MPP ultrafiltration membrane.

PMID- 15500747
TI  - [Development of HPV16 positive cervical cancer model in the hu-PBL-SCID mouse and
      its immunological features].
AB  - OBJECTIVE: To develop a HPV16 positive cervical cancer model in the hu-PBL-SCID
      mouse and investigate its immunological features. METHODS: Thirty-two CB17SCID
      mice were randomly divided into 4 groups: group A (5 mice) subcutaneously
      injected with phosphate-buffered saline, group B (5 mice) intraperitoneally
      injected with human peripheral blood lymphocyte (PBL) for immune reconstruction,
      group C (11 mice) subcutaneously injected with human cervical carcinoma cell line
      SiHa, and group D (11 mice) intraperitoneally injected with PBL and
      subcutaneously injected with SiHa cells after 24 hours of PBL transplantation.
      The tumor growth, behaviors and status of xenogeneic graft versus host disease
      (XGVHD) were observed. Human immunoglobulins G (IgG) in mouse serum, the
      percentage of human CD3(+), CD4(+) and CD8(+) T cells in peripheral blood and
      spleen, spleen weight, tumor infiltrating lymphocytes and human CD4(+) T cells,
      and cytotoxicity test of spleen cells were detected. RESULTS: The rate of
      successful tumor transplantation was 100%. XGVHD was not found. On the 5th day,
      human IgG level in the group B (0.98 microg/ml +/- 0.20 microg/ml) and group D
      (1.39 microg/ml +/- 0.25 microg/ml) was significantly higher than that in the
      group A (t = 7.655, 9.937, both P = 0.000). Human IgG level in group D was
      significantly higher than that in the group B (t = 3.200, P = 0.006). Only very
      low levels of human serumal IgG were detected in the group C and group A with no
      significantly difference. The level of human serumal IgG was gradually elevated
      in all the humanized SCID mice as the the time after PBL transplantation went on,
      and was significantly higher than that in non-humanized mice (P < 0.05). The
      percentage of human CD3(+), CD4(+) and CD8(+) T cells was significantly increased
      in the peripheral blood and spleen of immunoreconstituted SCID mice. The weight
      of spleen was markedly increased in the group D. TIL infiltrating in the tumor
      were remarkable and human CD4(+) T cells was detected by immunohistochemistry in
      the group D but not in the group C. The spleen cells in the group D displayed
      stronger cytotoxicity to the target cells (P < 0.05). CONCLUSION: Human immune
      function can be successfully reconstructed in SCID mouse via intraperitoneally
      injecting with human PBL, and induce anti-tumor immune response to the
      transplantated tumor of HPV16 positive cervical cancer.

PMID- 15500749
TI  - [Effect of 103palladium radioactive stent on expression of smooth muscle actin in
      bile duct during healing process and its significance].
AB  - OBJECTIVE: To observe the effect of radiation on the expression of smooth muscle
      actin (SMA) in the bile duct during the healing process and the inhibitory
      function of (103)palladium (Pd) radioactive stent on the stricture of bile duct
      after injury. METHODS: Twelve mongrel dogs were made models of bile duct injury:
      duodenotomy was performed, a balloon catheter was inserted into the general bile
      duct and saline with high pressure was perfused thereinto to cause laceration of
      the mucosa, and then the balloon catheter was withdrawn and ordinary alloy stent
      or (103)Pd radioactive stent was inserted into the general bile duct. Thirty days
      after the dogs were killed. Their bile ducts were taken out to undergo HE
      staining to observe the area of general bile duct, thickness of the tunica
      intima, area of residual bile duct cavity, stricture degree, and circumference of
      bile duct. The expression of SMA in the bile duct tissue was detected by
      immunoistochemistry. RESULTS: SMA was expressed in 5 of the 6 specimens of bile
      duct in the (103)Pd radioactive stent group and 2 of the 6 specimens of the
      ordinary stent group (P < 0.01). The maximum thickness of tunica intima of
      general bile duct was 0.78 mm +/- 0.12 mm in the (103)Pd radioactive stent group,
      significantly less than that of the ordinary stent group (1.86 mm +/- 0.14 mm, P
      < 0.01). The percentage of maximum stricture area of the (103)Pd radioactive
      stent group was 23% +/- 16%, significantly lower that that of the ordinary stent
      group (56% +/- 22%, P < 0.01). The circumference of bile duct cavity of the
      (103)Pd radioactive stent group was 9.7 mm +/- 1.6 mm, significantly longer that
      of the ordinary stent group (7.0 mm +/- 1.4 mm, P < 0.01). CONCLUSION: (103)Pd
      radioactive stent reduces the expression of SMA in the bile duct during the
      healing process, thus inhibiting the stricture of bile duct caused by scar
      contracture at the anastomotic stoma.

PMID- 15500748
TI  - [Role of connective tissue growth factor in angiotensin II induced human proximal
      tubular cell hypertrophy].
AB  - OBJECTIVE: Renal cell hypertrophy is an important compensatory mechanism of
      chronic renal diseases, which has been shown closely correlated with the
      activation of intrarenal renin angiotensin system. However, the exact mechanism
      is still uncertain. The present study was to investigate the role of connective
      tissue growth factor (CTGF) in mediating the effect of angiotensin (AngII)
      induced human proximal tubular cell (HK-2) hypertrophy. METHODS: The cell line,
      HK-2, was grown in Dulbeccos's Modified Eagle's Medium (DMEM) containing 10% heat
      inactivated fetal calf serum (FCS). After rested in serum-free medium for 24
      hours, The influence of anti-CTGF antibody on AngII induced cell protein de novo
      synthesis and total protein content were determined by [(3)H]-leucine
      incorporation and Coomassie brilliant blue G250 technique respectively.
      Fluorescence-activated cell sorter (FACS) flow cytometer was used to analyze the
      effect of anti-CTGF antibody on cell cycle distribution. The change of cellular
      size was determined by scanning electronic microscope (SEM). RESULTS: AngII
      significantly induced the increase of [(3)H] leucine incorporation in dose [AngII
      (mol/L): 0: 6926 +/- 1034; 10(-9): 8455 +/- 2137; 10(-7): 10 741 +/- 802; 10(-5):
      12 945 +/- 1377] and time [AngII (10(-7)mol/L): 0 h: 5584 +/- 1016; 24 h: 7379 +/
      957; 48 h: 10 741 +/- 802; 72 h: 16 606 +/- 1177] dependent manner. Meanwhile,
      the influence of AngII on cell total protein content showed the similar manner.
      Anti-CTGF antibody significantly inhibited the AngII induced above effects dose
      and time dependently. 48 h after the stimulation by AngII (10(-7)mol/L), the
      percentage of cells in G0-G1 phase (76.09% +/- 1.82%) and the average cell
      diameter (20.6 microm +/- 3.8 microm) was significantly increased compared to the
      control (62.1% +/- 2.5%, 11.9 microm +/- 1.6 microm, P < 0.01 respectively),
      which could markedly reversed by treatment with anti-CTGF antibody (71.68% +/-
      1.78%; 16.4 microm +/- 3.2 microm, P < 0.05, 0.01 respectively vs AngII group).
      CONCLUSION: AngII could induce the development of tubular cell hypertrophy, which
      might be mediated by CTGF.

PMID- 15500753
TI  - [Treatment of HELLP syndrome combined with multiple organ failure--a case
      report].

PMID- 15500752
TI  - [Pulmonary surfactant and respiratory failure].

PMID- 15500754
TI  - [Progress in the study of apolipoprotein A-V protein].

PMID- 15500755
TI  - [Ileum lymphoma--a case report].

PMID- 15500756
TI  - [MRI in the diagnosis of hip joint transient osteoporosis--a case report].

PMID- 15500758
TI  - [Myopia needs reasonable treatment].

PMID- 15500759
TI  - [Comparison of laser subepithelial keratomileusis and photorefractive keratectomy
      for the correction of myopia].
AB  - OBJECTIVE: To compare the effectiveness and difference between laser
      subepithelial keratomileusis (LASEK) and conventional photorefractive keratectomy
      (PRK) for the treatment of myopia up to -8.00 diopter. METHODS: In this
      prospective study, 46 patients with a manifest refactiion of -1.75 to -8.00
      diopters were treated and followed up for 6 months. In each case, PRK was
      performed in one eye and LASEK in the other eye. The first eye treated and
      surgical method used in the first eye was randomized. Epithelial healing time,
      postoperative pain, uncorrected visual acuity (UCVA), manifest refraction,
      corneal HAZE were followed and compared in PRK and LASEK treated eyes. RESULTS:
      LASEK eyes took a mean time of 3.49 days to heal the epithelium, whereas PRK eyes
      took 2.45 days, which is statistically significant (P <0.05). Postoperative pain
      index was 2.04 and 2.45 in LASEK eyes and PRK eyes respectively (P <0.05). There
      were no significant differences between eyes in UCVA and manifest refraction
      during the follow time (P >0.05). However, LASEK-treated eyes showed less corneal
      haze than PRK eyes. CONCLUSIONS: LASEK can effectively and safely treat myopia up
      to -8.00 diopters as PRK did, and can diminish early pain after surgery and
      prevent corneal Haze from happening.

PMID- 15500760
TI  - [A study on difference of ocular motor parameters in myopia].
AB  - OBJECTIVE: This study sought to assess the difference of these ocular motor
      parameters in myopia onset and development were explored. METHODS: 31 emmetropia
      and 46 myopia adult subjects were included in this study. The myopia subjects
      were divided into three groups as mild myopia, moderate myopia and high myopia.
      Phoria at distance and near, positive and negative relative accommodation
      (NRA/PRA) were measured. Accommodative convergence and accommodation stimulus
      ratio (AC/A) was determined through phoria values' calculation. RESULTS:
      Calculated AC/A of myopia was higher than that of emmetropia, and there were
      trends of elevated AC/A with myopia power increasing. There was significant
      difference in phoria in near between the myopia group and emmetropia group, but
      none in that of distance. There was no significant difference in NRA. However,
      PRA of myopia was lower than that of the emmetropia (P <0.05). CONCLUSIONS:
      Ocular motor parameters are different in myopia eyes. AC/A is one of key
      parameters among them, and AC/A is increased in myopia, which indicates out of
      focus of retinal image in the developing myopia.

PMID- 15500761
TI  - [Phototherapeutic keratectomy combined with photorefractive keratectomy for the
      treatment of myopia with corneal scars].
AB  - OBJECTIVE: To evaluate the effects of phototherapeutic keratectomy (PTK) combined
      with photorefractive keratectomy (PRK) in the treatment of myopia with corneal
      scars. METHODS: Corneal epithelium was removed with laser plus scraping (d=7.0
      mm). Corneal scars were removed with PTK (d=7.0 mm) and followed by PRK for
      myopia (d=6.0 mm). Healon was used to make corneal surface smoother during
      operation. RESULTS: 79 eyes of 54 cases of myopia with corneal scars were
      followed up at least for one year. Mean refractive degree was (-6.73 +/- 4.17) D
      and corrected vision was 0.63 before operation. After operation,corneal scars in
      50 eyes (63.3%) were removed in operative zone and corneal haze was less than I
      degree. The vision acuity in 69 eyes (89.9%) was equal to or better than
      preoperative best correction. Mean postoperative vision was 0.74. Corneal surface
      was smoother and astigmatism was reduced after surgery. CONCLUSION: PTK combined
      with PRK is a safe and effective treatment for myopia with corneal scars.

PMID- 15500762
TI  - [Dynamic changes of configuration and position of human ciliary body during
      accommodation].
AB  - OBJECTIVE: To study the changes of the configuration and position of ciliary body
      of normal human eyes in spontaneous far and near accommodations. METHODS: The
      configuration and position in ciliary body of 68 normal human eyes were observed
      real-timely and measured by high frequency transducer of ultrasound biomicroscopy
      (UBM), when these eyes focused on given far and near optotypes, respectively. All
      of these parameters between far and near accommodations were compared by One-Way
      Analysis of Variance (One-Way ANOVA) and Multivariate ANOVA of General Linear
      Model (MANOVA of GLM), and were correlated with each other respectively
      (alpha=0.05). RESULTS: (1) In near accommodation, there were statistically
      significant increase in the thickness of anterior ciliary body, length of ciliary
      process, whole area of ciliary body and area of circular fibers. There were
      statistically significant decreases in width of ciliary process, angle of inner
      apex, distances between ciliary process and trabecula, iris, scleral spur, and
      angles between ciliary process and iris, ciliary process and sclera; there was
      also a certain decrease in angle-opening distance 500 microm from the scleral
      spur. There were no significant changes in the thickness of posterior ciliary
      body; area of meridional fibers; angle between sclera and iris and angle between
      trabecula and iris. (2) Parameters of configuration had close correlation with
      each other, and it was also true in those of position. But, the correlation
      between the configuration and position was not significant. CONCLUSIONS: In the
      process of near accommodation, ciliary body shifts forwards and inwards, ciliary
      process becomes tapered because the harmonious contraction of its circular and
      meridional muscle fibers. This is consistent with the classical relaxation
      mechanism of accommodation described by Helmholtz. UBM is a new noninvasive
      method for real-time studying of the ciliary body changes in far-near
      accommodating human eyes in vivo.

PMID- 15500763
TI  - [The image futures of optical coherence tomography in pathologic myopia].
AB  - OBJECTIVE: To study the characteristics of optical coherence tomography (OCT)
      pictures in pathologic myopia. METHODS: 100 cases (195 eyes) of pathologic myopia
      were examined with OCT. The Age ranges of all the cases was 16-76 years and
      refraction error was -6.00 - -36.00 diopters. RESULTS: OCT image was normal in 7
      eyes (4.3%), the reflectivity band of RPE and chorio-capillaries were uneven and
      thinning in 147 eyes (90.2%). Full-thickness macular hole was found in 21 eyes
      (10.8%), of which 10 (5.1%) eyes were associated with retinal detachment; local
      shallow retinal detachment was found in 24 eyes (12.3%), of which 7 eyes (3.6%)
      were associated with retinal schisis, 19 eyes (9.7%) with macular choroidal
      neovascularization (CNV). retinal swelling was often associated with the
      following diseases: Fuchs spot 9 eyes (4.6%), thick macular hemorrhage 3 eyes,
      epiretinal macular membrane 18 eyes (9.2%); macular sensory retina thinning in 5
      eyes (2.6%). CONCLUSION: Compared with fundus examination including slit lamp
      with pan-retinoscope, OCT showed unique preference for observation of the changes
      of retinal pigment epithelium (RPE), chorio-capillary layer, diagnosis macular
      hole and epiretinal macular membrane, discovery of small sensory retinal
      detachment, schisis and thinning of sensory retina layer etc. OCT can not either
      discover a piece of thin macular hemorrhage or differentiation between thick
      macular hemorrhage and pigment spot.

PMID- 15500764
TI  - [Effects of flashing light on ocular growth and development of myopia in
      pigmented guinea pigs].
AB  - OBJECTIVE: To investigate the effects of flashing light exposure on ocular growth
      and development of myopia in guinea pigs. METHODS: Thirty 4-week-old pigmented
      guinea pigs were randomly divided into three groups. Animals in group I were
      reared with the flashing light continuously and lasted for 6 weeks. The flashing
      frequency was 15 times per minutes and every flash includes 2 seconds light on
      and 2 seconds dark. Animals in group II and III were reared with normal light on,
      and the illumination cycle was 12 hours light/12 hours dark in group II and 24
      hours light in group III. After 6 weeks, the effects of flashing light on eye
      development were assessed by cycloplegic retinoscopy, a-scan ultrasonography and
      eye weight. The histopathology changes of sclera, choroids and retina in
      posterior pore of the eye were examined using light microscope and transmission
      electron microscope. RESULTS: At the end of the treatment period, guinea pigs
      reared in flashing light exhibited -7.00 D myopia, eye axial elongated 0.56
      microm, and the weight increased 68 mg. The histopathology examination showed
      that the posterior sclera fibroblast become more active, the cell number
      increased, and the place between fibers became larger, the posterior choroids
      became thinned, and the outer membrane of photoreceptor cells became shorter and
      irregular, when compared with the control groups. CONCLUSION: Flashing light can
      promote ocular growth and induce myopia in pigmented guinea pigs.

PMID- 15500765
TI  - [Black diaphragm intraocular lens for congenital aniridia or traumatic iris
      deficiency].
AB  - OBJECTIVE: To evaluate the efficacy of a black diaphragm intraocular lens (IOL)
      implantation for congenital aniridia or traumatic iris deficiency and to explore
      the mechanism of postoperative complications. METHODS: The therapeutic effects
      and postoperative complications of twenty-five cases (27 eyes) of black diaphragm
      intraocular lens implantation were analyzed. Ultrasound biomicroscope (UBM) and
      gonioscopy were used to observe the position of the IOL haptics and anterior
      chamber angle structure in patient who developed secondary glaucoma
      postoperatively. RESULTS: After 3-18 months of follow-up, photophobia was reduced
      or disappear. The best corrected visual acuity (BCVA) Postoperation was improved
      2 lines in 20 eyes, no change or within 1 line in 5 eyes, decreased 2 lines or
      more in 2 eyes. The complications included secondary glaucoma (10 eyes, 37.0%),
      astigmatism (17 eyes, 63.0%), corneal decompensation (2 eyes, 7.4%), hyphema (2
      eyes, 7.4%), vitreous hemorrhage (3 eyes, 11.1%), and retinal detachment (1 eye,
      3.7%). Of the 20 haptics in 10 patients, 9 were adequately located in the sulcus
      region, the others were located in chamber angle, ciliary processes or posterior
      to the ciliary processes. The changes of chamber angle included angle recession,
      anterior adhesion of iris and angle closure. CONCLUSIONS: The black diaphragm
      intraocular lens implantation provides an effective method in the treatment of
      congenital aniridia or traumatic iris deficiency. Chamber angle impair is major
      cause of postoperative secondary glaucoma. Abnormality of lens haptics position,
      hemorrhage and persistent inflammation were also play a role in secondary
      glaucoma.

PMID- 15500766
TI  - [Analysis of the quality of clinical trials about therapeutic research using the
      standard of evidence-based medicine].
AB  - OBJECTIVE: To investigate the quality of clinical trials of ocular therapeutic
      efficacy in China in order to provide the facts to support the Evidence-Based
      Medicine (EBM) and improve the clinical research trials. METHODS: All the
      articles published in Chinese Journal of Ophthalmology from 1983 to 2002
      emphasizing random control trial and clinical control trial were evaluated as per
      EBM standard. RESULTS: The total number of articles for clinical therapeutic
      efficacy published in the past 20 years were 152, of which 35 articles (23.0%)
      were random control trials, and 8 (5.3%) articles were clinical control trials.
      The disparity of quality of research was found as follows. The method of
      random/half random was described in 10 articles (23.3%). Placebo-control and open
      control were reported in 3 (3/43) and 9 articles (20.9%), respectively. Blinded,
      double-blinded, and single-blinded research was adopted in 7 (16.3%), 3 articles
      (7.0%), and 4 articles (9.3%), respectively. Ten articles (23.3%) reported strict
      diagnostic standard including inclusion and exclusion standards while 30 articles
      (69.8%) didn't use exclusion criteria. Follow-up visits from a few months to
      years was found in 30 out of 43 articles, of 25 articles (58.1%) provided
      detailed follow-up visit data; 19 articles (44.2%) didn't supply any information
      of the cases lost follow-up, only 7 articles (16.3%) reported the cause and
      process of the cases lost follow-up. Adverse events were not consistently
      reported in the articles. Not a single article estimated sample size when the
      study was designed. Most articles included small or medium size samples, while
      lacking of multi-center, large sample, randomized, double-blinded and placebo
      controlled clinical trials. Statistical significance for either part or all data
      except P value was not indicated in 15 articles (34.9%). The indexes assessing
      the clinical significance of clinical therapeutic efficacy include relative risk
      reduction, absolute risk reduction, number needed to treat, however, these
      indexes were not used in all the articles. CONCLUSIONS: In summary, the clinical
      trials related to ocular therapeutic efficacy published between 1983 and 2002
      were not very well designed and the accuracy and the reliability of the results
      were greatly affected. Therefore, it is imperative to improve the quality of the
      research by enhancing the design and analysis of the research in future.

PMID- 15500767
TI  - [The effect of endothelial leukocyte-adhesion molecule-1 on the shape and
      cytoskeleton of porcine trabecular meshwork cells].
AB  - OBJECTIVE: To study the effects of endothelial leukocyte-adhesion molecule-1
      (ELAM-1) on the shape and actin cytoskeleton of cultured porcine trabecular
      meshwork cells (PTCs). METHODS: The cultured PTCs were stimulated by interleukin
      1 (IL-1) and conjugated by ELAM-1 antibody or further cross-linked by IgG.
      Immunocytochemical procedures were used to study the expression of ELAM-1 and
      FITC-phalloidin was used to stain the actin filaments on PTCs; phase contrast
      microscope was employed to observe the dynamic changes of cellular shape and the
      intercellular conjunction and confocal microscope was used to observe the changes
      of actin and cellular thickness. RESULTS: IL-1 treatment increased the expression
      of ELAM-1 in PTCs which resulted in enlarged intercellular space in PTCs with
      more rounded and stereoscopic morphology after specific antibody conjugation or
      IgG cross linking. In addition, actin filaments became sparse, cellular rigidity
      decreased, and the cellular thickness increased after these treatments.
      CONCLUSIONS: Our results demonstrated that IL-1 activated PTCs can express ELAM-1
      and interaction of ELAM-1 with specific antibodies and cross linking with IgG,
      induced a rounding-up of PTCs. This change in cell shape may be due to its action
      on the actin cytoskeleton.

PMID- 15500768
TI  - [The expression of cluster of differentiation 44 variant 6 and fibronectin in
      lacrimal gland tumors].
AB  - OBJECTIVE: To investigate the expression of cluster of differentiation 44 variant
      6 (CD44V6) and fibronectin (FN) in lacrimal gland tumors. METHODS: Strept Avidin
      Biotin Complex (SABC) immunohistochemistry method was used to study the
      expression of CD44V6 and FN in 49 cases of lacrimal gland tumors. RESULTS: In
      benign lacrimal gland tumors, the CD44V6 and FN positive rates were 30.8% (8/26)
      and 80.8% (21/26) respectively. In malignant lacrimal gland tumors, the CD44V6
      and FN positive rates were 60.9% (14/23) and 34.8% (8/23). The positive
      expression rates of CD44V6 and FN in malignance were significantly different from
      benign and control tissue. There is also a significant difference in the
      expression of CD44V6 and FN in the cases of recurrence and non recurrence (P
      <0.05). CONCLUSIONS: The expression of CD44V6 and FN was correlated with the
      progress and recurrence of lacrimal gland tumors. The positive staining of CD44V6
      and FN was useful for differentiating malignance from benignity and evaluating
      the progress and recurrence.

PMID- 15500769
TI  - [Posterior vitreous detachment induced by intravitreal injection of the
      combination of chondroitinase ABC and matrix metalloproteinase-3].
AB  - OBJECTIVE: To investigate the occurrence of enzymatic induction of posterior
      vitreous detachment (PVD) by the combination of Chondroitinase ABC (CA) and
      matrix metalloproteinase-3 (MMP-3), so as to seek a noninvasive and effective
      pharmacologic approach to facilitate and eventually replace the present
      mechanical vitreous surgery. METHODS: Twenty-four pigmented rabbits were randomly
      assigned to two groups of twelve each, the experimental group was treated with CA
      (0.2 U) and MMP-3 (10 ng) combination, the control group was received equivalent
      dose of balanced salt solution (BSS). Clinical examinations and
      electroretinography were performed before and after injection. Over a different
      period of time, the rabbits were euthanized and killed and their eyes were
      examined histologically. RESULTS: The foci of partial synchisis and clinically
      named PVD were recognized for the first time three days after injection. Complete
      liquefaction was found in every eye of experimental group, and in which, 5/8 eyes
      developed clinically detected PVD one week after injection Histologic section
      showed PVD with various extent in 3/7, 7/7, 7/7 eyes of experimental group 30
      minutes, 60 minutes and one week after injection respectively, and complete PVD
      in 0/7, 1/7, 5/7 eyes of experimental group at the same periodic intervals as
      above. By contrast, no vitreous liquefaction was found and only one eye showed
      confined partial PVD in the control group. Clinic, electrophysiologic and
      histologic evaluation in all rabbits revealed no evidence of ocular toxicity.
      CONCLUSIONS: Vitreous 1iquefaction and PVD can be produced shortly after
      intravitreal injection using a combination of CA and MMP-3, and the two enzymes
      were cooperative. Synchisis and weakening of vitreoretinal adherence were almost
      simultaneously. The dose of 0.2 U CA and 10 ng MMP-3 combination proved to be
      safe and ideal selection to induce PVD.

PMID- 15500770
TI  - [Attention to the research on airway remodeling and its pathogenesis in chronic
      obstructive pulmonary disease].

PMID- 15500771
TI  - [The foundation of clinical training in budding clinicians].

PMID- 15500772
TI  - [Value and importance of the general department of internal medicine in
      hospital].

PMID- 15500773
TI  - [Respiratory control in obstructive sleep apnea hypopnea syndrome].
AB  - OBJECTIVE: To evaluate the role of ventilatory control in obstructive sleep apnea
      hypopnea syndrome (OSAHS). METHODS: Thirty-five patients with OSAHS were compared
      with 15 obese controls in pulmonary function, hypoxic ventilatory response (HVR),
      hypercapnic ventilatory response (HCVR) and polysomnography (PSG). RESULTS: (1)
      There were no differences in HVR and HCVR between patients with OSAHS and the
      control (t = 1.28, 0.57; P > 0.05). In OSAHS patients, HVR was correlated with
      nadir nocturnal oxygen saturation (MmS(P)O(2)) (r = -0.54, P < 0.01) and HCVR (r
      = 0.57, P < 0.01). (2) Patients with mild and moderate OSAHS had higher HVR than
      those with severe OSAHS (t = 2.74, P < 0.01). When 5 < or = apnea and hypopnea
      index (AHI) < 40, HVR was negatively correlated to forced expiratory volume in
      one second (FEV(1))/peak expiratory flow (PEF) (r = -0.42, P < 0.05) and AHI (r =
      -0.68, P < 0.01). For those whose AHI > or = 40, HVR was negatively correlated
      with MmSpO(2) (r = -0.58, P < 0.05) and positively correlated with HCVR (r =
      0.59, P < 0.05). CONCLUSION: In OSAHS patients, HCVR did not show significant
      change, but HVR showed two phasic change-increase first and then decrease
      following the elevation of AHI, which was also related to MmSpO(2) and HCVR.

PMID- 15500774
TI  - [Short-term and long-term influences of nasal continuous positive airway pressure
      to sleep architecture of obstructive sleep apnea hypopnea syndrome].
AB  - OBJECTIVE: To observe the short-term and long-term influences of nasal continuous
      positive airway pressure (nCPAP) to sleep architecture of obstructive sleep apnea
      hypopnea syndrome (OSAHS). METHODS: Thirty cases who were diagnosed as OSAHS
      patients by polysomnography (PSG) were enrolled in the study. They received the
      nCPAP treatment in hospital at first night and then at home. Seventeen healthy
      adults were enrolled as control group and experienced PSG monitoring and
      recording. The sleep architectures of control group and OSAHS group (before
      nCPAP, first night on the nCPAP and 6 months after continuous nCPAP treatment)
      were analysed. RESULTS: The sleep shift number, first stage sleep, second stage
      sleep, stage of slow wave sleep and stage of rapid eye movement (REM) sleep were
      34.41 +/- 10.16, (5.95 +/- 3.89)%, (48.13 +/- 7.68)%, (18.30 +/- 4.71)%, and
      (26.83 +/- 6.65)%, respectively, in control group. These parameters in OSAHS
      group before nCPAP were 207.30 +/- 149.80, (21.42 +/- 10.17)%, (55.24 +/-
      13.28)%, (15.38 +/- 19.57)%, and (10.15 +/- 7.82)%, respectively. At the first
      night of nCPAP treatment they were 55.77 +/- 25.04, (10.92 +/- 9.62)%, (50.19 +/-
      13.34)%, (17.53 +/- 10.06)%, and (21.17 +/- 7.66)%, respectively. There were
      statistically significant differences between the PSG parameters before and after
      nCPAP treatment in OSAHS group (P < 0.05). After 6 months of nCPAP treatment, the
      stage of REM sleep was significantly shorter (P < 0.05), but the other parameters
      had no significant changes compared with those at the first night on nCPAP (P >
      0.05). CONCLUSION: The sleep shift number and first stage sleep in OSAHS group
      were significantly increased, but the stage of REM sleep was significantly
      decreased than those in control group. The sleep architecture of OSAHS was
      significantly improved when the nCPAP treatment was given continuously.

PMID- 15500775
TI  - [Ventilator-associated pneumonia caused by Pneumocystis carinii in the non-human
      immunodeficiency virus infection: a report of 5 cases].
AB  - OBJECTIVE: To comprehend ventilator-associated pneumonia (VAP) caused by
      pneumocystis carinii (P. carinii-VAP) in the non-human immunodeficiency virus
      (HIV) infected patients. METHODS: The clinical data of 5 patients with P. carinii
      VAP in the non-HIV patients from 2000 to 2003 in our hospital were reviewed.
      RESULTS: Five male patients, aged 71 - 93, had severe predisposing diseases and
      respiratory failure induced by lung infection. All patients were treated with
      mechanical ventilation and multiple antibiotics and had recurrent VAP. Fever was
      present in all patients together with respiratory symptoms. Moist rales were
      noted in four of them. X-ray showed diffuse patchy shadows in 4 patients,
      extensive densities in 1 cases, reticular infiltrations in 2 cases, and pleural
      effusion in 2 cases. Sputum P. carinii was found by smear staining in 4 cases as
      well as a positive PC PCR. The remaining case only showed a positive PC PCR. Four
      patients were cured after treatment with SMZco, but one patient died. CONCLUSION:
      P. carinii-VAP could occur during prolonged mechanical ventilation for severe
      respiratory diseases, particularly in aged patients with advanced cancer or
      treated with glucocorticoids and broad spectrum antibiotics.

PMID- 15500776
TI  - [Influence factors on diagnosis and prognosis of thymoma: analysis of 135 cases].
AB  - OBJECTIVE: To investigate the clinical features and prognostic factors of
      thymoma. METHODS: 135 patients with a diagnosis of thymoma or thymic carcinoma
      were identified in Peking Union Medical University Hospital from Jan, 1990 to
      Feb, 2003. Their clinical presentation and prognostic factors were analyzed.
      RESULTS: Of the 135 patients, 21 (15.6%) were asymptomatic and 66 (48.9%)
      presented symptoms consistent with myasthenia gravis. Venous obstruction, male
      gender and longer disease course appeared to be the predisposing factors of
      malignancy (chi(2) = 8.373, P = 0.004; chi(2) = 6.125, P = 0.013; U = 1691.5, P =
      0.013 respectively). Calcification and necrosis on radiological findings did not
      differentiate thymoma from thymic carcinoma. Tumor recurrence was related to the
      Masaoka stage and the course of disease by logistic method [Exp(b) = 1.050,
      6.728, P = 0.038, 0.003]. The recurrence rate was 2.7% in stage I, 11.1% in stage
      II, 30.4% in stage III, and 83.3% in stage IV. CONCLUSIONS: Thymoma has a
      variable clinical manifestation. Clinical outcome is correlated with Masaoka
      stage and early tumor resection. Radiographic findings are not reliable in the
      differentiation of benign tumor from malignancy.

PMID- 15500777
TI  - [Study on hemodynamic changes and cardiac troponin I level in pig model of acute
      experimental pulmonary embolism].
AB  - OBJECTIVE: To evaluate the hemodynamic effects and cardiac troponin I (cTn I),
      creatine kinase-MB (CK-MB), myoglobin (Mb) releasing kinetics of acute
      experimental pulmonary embolism of pigs. METHODS: Sixteen juvenile pigs, of
      either gender and weighing 30 to 40 kg were studied, 8 in the embolism group and
      8 in the control group. The 8 embolism animals received 0.1 g/kg polystyrene
      beads (diameter range 0.65 to 0.67 mm) suspended in 0.9% saline by venous
      injection. Pulmonary arterial pressure (PAP), systemic arterial pressure (SAP),
      pulmonary capillary wedged pressure (PCWP), cardiac output (CO), blood gases and
      serum cTn I, CK-MB, and Mb were measured before and immediately, 30 min, 1 hour,
      2 hour, and 3 hour after acute pulmonary embolism. RESULTS: PAP was increased to
      2 - 3 fold of the baseline and the control level immediately, and then decreased
      to the baseline level in 2 to 3 hours. Serum cTn I and Mb increased significantly
      after embolism and remained at a higher level through the 3 hour experimental
      procedure. The CK-MB was not changed after acute pulmonary embolism. CONCLUSIONS:
      Acute pulmonary embolism caused lung gas exchange abnormality and acute pulmonary
      hypertension. The hemodynamic effects of acute pulmonary embolism include injury
      to the myocardial cells and releasing of cTn I and Mb to blood stream. cTn I can
      be detected in the early phase of acute pulmonary embolism, and maybe a useful
      marker in diagnosis and management of acute pulmonary embolism.

PMID- 15500778
TI  - [Screening for low-density lipoprotein receptor gene mutations in familial
      hypercholesterolemia Chinese].
AB  - OBJECTIVE: To screen the mutations of low-density lipoprotein receptor (LDLR)
      gene in Chinese familial hypercholesterolemia (FH) patients. METHODS: 7 patients
      with clinical phenotype of homozygous FH and their parents were investigated for
      mutations in all the eighteen exons of LDLR gene. Screening was carried out using
      PCR-SSCP and direct DNA sequencing and LDLR gene mutation database was searched
      to identify the alteration. In addition, the apolipoprotein B gene (apo B) was
      screened for known mutations (R3500Q) that caused familial defective apo B100
      (FDB) with polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP). RESULTS: Nine mutations in the LDLR gene were identified in the FH
      patients. All the mutations except C255R have not been published in the LDLR gene
      mutation database. No mutation of apo B100 (R3500Q) was observed. CONCLUSIONS:
      Chinese FH patients may have specific spectrum and regional difference of LDLR
      gene mutations. Apolipoprotein B-100 gene mutation might not be the main cause of
      hypercholesterolemia patients in China.

PMID- 15500779
TI  - [Factors related to false positive results of treadmill electrocardiogram test
      for the detection of coronary heart disease].
AB  - OBJECTIVE: To investigate the clinical factors related to false positive results
      of electrocardiogram treadmill exercise test (TET) for the detection of coronary
      heart disease (CHD). METHODS: 258 patients with chest pain undergoing TET and
      coronary angiography (CAG) were on rolled. The case history and various clinical
      parameters were collected. (1) The results of TET and CAG were compared to
      evaluate the sensitivity, specificity and accuracy of TET; (2) Clinical
      informations of the true positive group and the false positive group were
      compared and a statistic analysis was carried out. RESULTS: The sensitivity,
      specificity and accuracy of TET for diagnosing CHD was 77.3%, 65.9%, and 69.8%
      respectively. The number of female in the false positive group was larger than
      that in the true positive group; The number of patients with typical chest pain,
      hyperlipidemic history, smoking history and family history of CHD was smaller
      than that in the true positive group. In the false positive group, the change of
      ST segment was mainly in II, III, aVF. The number of patients with change of more
      than 0.2 mV in ST and with angina induced during exertion was lower in the false
      positive group than in the true positive group. The difference was significant.
      CONCLUSION: Factors including sex, typical chest pain, risk factors of CHD, the
      location and extent of ECG changes and angina induced by exertion are closely
      related to false positive results of TET.

PMID- 15500780
TI  - [The clinical features of acute pancreatitis in 10 cities in Shandong Province].
AB  - OBJECTIVE: To investigate and obtain a more comprehensive view of the etiology
      and clinical features of acute pancreatitis (AP) in Shandong Province. METHODS:
      1471 cases admitted to hospital for AP were studied and collected from the ten
      cities of Shandong Province from January 1992 to December 2002 retrospectively.
      Data of each enrolled patient was recorded in a standardized form. RESULTS: In
      the 1471 patients, the ratio of male: female was 854:617, and also the mean age
      of them and the range was 43.3 and from 13 - 82 years old. 1280 had mild AP, and
      191 had sever AP. Cholelithiasis (20.2%), alcohol (17.3%) and diet-induced
      (12.4%) were the most frequent etiologic factors, followed by biliary tract
      infections (5.6%), hyperlipemia (2.3%), other factors (5.1%). But in about 36.1%
      cases, the etiology of AP still remains unexplained. In coastal regions,
      cholelithiasis is the most frequent factor but in interior regions alcohol ranked
      first. In male, a small predominance of alcohol over cholelithiasis was seen
      (27.4 vs.14.3%, P < 0.01); and in female, there was a clear predominance of
      cholelithiasis over alcohol (28.4 vs. 3.2%, P < 0.01). The complications of AP
      were pancreatic pseudocyst, ascites and peritonitis, pulmonary infections,
      multiple organ failure, diabetes mellitus-2 and shock, etc. according to their
      frequencies. CONCLUSIONS: Cholelithiasis, alcohol and diet-induced factor were
      main etiologic factors in Shandong Province, whereas cholelithiasis alone
      predominated in the females. In about 36.1% cases, the etiology remains unknown.
      So that more attention should be paid to study the etiology of AP.

PMID- 15500781
TI  - [The relationship between serum calcitonin gene-related peptide, sex hormone,
      homocysteine and coronary artery disease in postmenopausal women].
AB  - OBJECTIVE: To investigate the relationship between serum calcitonin gene-related
      peptide (CGRP), homocysteine (Hcy), sex hormone, and coronary heart disease (CHD)
      in postmenopausal women. METHODS: In a cross-sectional study, serum CGRP,
      estradiol (E(2)), progesterone (P) and Hcy levels of 144 postmenopausal women
      undergoing diagnostic CHD (75 with CHD and 69 without CHD) and 66 healthy young
      women were measured. RESULTS: The occurrence of CHD was correlated with high Hcy
      level and low CGRP level. The mean serum CGRP level was significantly lower in
      CHD postmenopausal women than in without CHD ones [(103.6 +/- 59.8) ng/L vs
      (164.6 +/- 50.7) ng/L, P < 0.01]. The mean serum E(2) level was significantly
      lower in CHD postmenopausal women than in without CHD ones [(67.9 +/- 24.4)
      pmol/L vs (91.7 +/- 23.0) pmol/L, P < 0.01]. The mean serum P level was
      significantly lower in CHD than in without CHD postmenopausal women [(0.89 +/-
      0.46) nmol/L vs (1.11 +/- 0.45) nmol/L, P < 0.01]. The mean serum Hcy level was
      significantly higher in CHD than in without CHD postmenopausal women [(15.3 +/-
      6.5) micromol/L vs (10.2 +/- 2.8) micromol/L, P < 0.01]. By multivariate logistic
      regression, the OR of high Hcy level > or = 1, P < 0.01, that means Hcy is an
      independent risk factor of CHD. The OR of CGRP, E(2) and P were all < or = 1,
      indicating that they were independent protective factor. CONCLUSIONS: Hcy is an
      independent risk factor of CHD. CGRP, E(2) and P are independent protective
      factors of CHD. There was no relationship between Hcy, CGRP and E(2) and P.

PMID- 15500782
TI  - [A clinical review of 449 cases with fever of unknown origin].
AB  - OBJECTIVE: To investigate the causes of fever of unknown origin (FUO). METHODS:
      The clinical data were retrospectively analyzed from patients with FUO
      hospitalized in Peking Union Medical College Hospital from January 2000 to
      December 2003. During that period of time, 449 cases fulfilled the criteria of
      FUO. RESULTS: Out of the 449 FUO cases, definite diagnosis was eventually
      achieved in 387 patients (86.9%). The most common causes of FUO were infectious
      diseases (56.8%), with tuberculosis accounting for 43.6% of cases of infection.
      Seventy-six patients were suffered from collagen vascular diseases (CVD): with
      Still's disease, systemic lupus erythematosus and vasculitis accounting for 34.2%
      (26/76), 18.4% (14/76) and 13.2% (10/76) of the this category, respectively.
      16.5% (64/449) of the FUO cases were diagnosed as malignancy. Miscellaneous
      causes were found in 7.0% of the FUO cases. However, no definite diagnosis had
      been made in the remaining 62 (13.8%) cases until they discharged from the
      hospital. CONCLUSIONS: In most FUO cases the causes can be diagnosed eventually
      after careful analysis of clinical data. While infectious diseases, especially
      tuberculosis, were still the most common causes of FUO, CVD and malignancy were
      also major causes of FUO and the incidence of malignancy were increased with the
      time.

PMID- 15500784
TI  - [The clinical and pathological features of rhinocerebral mucormycosis].
AB  - OBJECTIVE: To investigate the clinical and pathological features of rhinocerebral
      mucormycosis. METHODS: The clinical data of three cases of mucormycosis were
      collected and analyzed. Pathological examination was conducted by autopsy or
      biopsy. RESULTS: All the three cases of mucormycosis had diabetic ketoacidosis.
      The early symptoms were fever, periocular and temporal headache. Gradually,
      orbital apex syndrome, periocular skin cellulitis and necrosis developed.
      Examination of nose revealed black necrotic turbinates. Meningeal signs and
      hemiplegia may also occur. Frontal hemorrhagic infarction was seen in pathology.
      A large amount of mucor fungi were found in the mucosa of nasal sinuses necrotic
      brain tissue under microscope. CONCLUSIONS: Rhinocerebral mucormycosis is a rare
      complication which was mainly seen in patients with diabetic ketoacidosis. The
      lesion invaded nose, eyes and brain with a high mortality.

PMID- 15500785
TI  - [Detection and purification of cytokine secreting T lymphocytes in allogeneic
      reaction and a preliminary study on its clinical significance].
AB  - OBJECTIVE: Detection of cytokine secreting T lymphocytes after allogeneic
      peripheral blood mononuclear cell (PBMNC) stimulation was carried out and its
      clinical significance discussed so as to explore a new approach to study
      allogeneic reactive T lymphocytes. METHODS: Cytokine secretion assay (CKSA) was
      applied to detect T lymphocytes secreting interferon gamma (IFNgamma),
      interleukin-4 (IL-4) and IL-10 at single cell level in human mixed lymphocytes
      reaction. T cells secreting IFNgamma from PBMNC were detected in patients with
      acute graft versus host disease (aGVHD). RESULTS: In comparison with T cells
      secreting IL-4 and IL-10 which were (0.12 +/- 0.03)% and (0.10 +/- 0.03)%,
      respectively, a sizable proportion of T cells secreting IFNgamma could be
      detected (1.12 +/- 0.13)%. Preliminary result indicated that frequency of T cells
      secreting IFNgamma correlated with the occurrence of aGVHD. CONCLUSIONS: It is
      feasible to detect T lymphocytes secreting IFNgamma after allogeneic PBMNC and to
      apply CKSA technique for clinical research.

PMID- 15500805
TI  - The force of symmetry revisited: symmetry-to-noise ratios regulate (a)symmetry
      effects.
AB  - Freyd and Tversky's [Am. J. Psychol. 97 (1984) 109] data suggested that human
      observers tend to overestimate relatively high levels of symmetry (symmetry
      effect), and tend to underestimate relatively low levels of symmetry (asymmetry
      effect). However, on the basis of their holographic approach to visual
      regularity, van der Helm and Leeuwenberg [Psychol. Rev. 103(3) (1996) 429]
      predicted that, at any level of symmetry, both symmetry and asymmetry effects may
      occur as a consequence of correct estimates of symmetry-to-noise ratios. This
      prediction was tested in two experiments, with tasks and stimuli similar to those
      in Freyd and Tversky's study. First, subjects had to judge whether a noisy
      symmetry is more similar to a slightly more symmetrical variant or to a slightly
      less symmetrical variant. Second, for every pair of stimuli in such a triadic
      comparison, subjects had to judge which stimulus is the more symmetrical one. The
      results from both experiments show that the occurrence of (a)symmetry effects
      indeed depends on symmetry-to-noise ratios.

PMID- 15500806
TI  - Actor-observer differences in realism in confidence and frequency judgments.
AB  - Taking a social psychological approach to metacognitive judgments, this study
      analyzed the difference in realism (validity) in confidence and frequency
      judgments (i.e., estimates of overall accuracy) between one's own and another
      person's answers to general knowledge questions. Experiment 1 showed that when
      judging their own answers, compared with another's answers, the participants
      exhibited higher overconfidence, better ability to discriminate correct from
      incorrect answers, lower accuracy, and lower confidence. However, the
      overconfidence effect could be attributable to the lowest level of confidence.
      Furthermore, when heeding additional information about another's answers the
      participants showed higher confidence and better discrimination ability. The
      overconfidence effect of Experiment 1 was not found in Experiment 2. However, the
      results of Experiment 2 were consistent with Experiment 1 in terms of
      discrimination ability, confidence, and accuracy. Finally, in both experiments
      the participants gave lower frequency judgments of their own overall accuracy
      compared with their frequency judgments of another person's overall accuracy.

PMID- 15500807
TI  - Time pressure effects on information processing in overlapping tasks: evidence
      from the lateralized readiness potential.
AB  - Information processing is impaired when two tasks are performed concurrently. The
      interference between the tasks is commonly attributed to structural bottlenecks
      or strategic scheduling of information processing. The present experiment
      investigated the effects of time pressure for the second of two responses on
      information processing in overlapping tasks by recording the lateralized
      readiness potential (LRP). Time pressure shortened the latency of the second
      response by diminishing the time devoted to motoric processing. In addition, task
      interference decreased under time pressure, which is probably due to the
      relatively early availability of the central bottleneck stage rather than to
      increased overlap of central stages. The LRP also provided direct evidence for an
      additional bottleneck following response selection, possibly due to supramodal
      refractoriness of response initiation.

PMID- 15500808
TI  - Temporal performance in 4-8 year old children. The effect of chronometric
      information in task execution.
AB  - The present study explores temporal performance in children between 4 and 11
      years of age. In order to optimise the children's performance, verbal
      instructions and demonstrations were used to specify the temporal requirement of
      the task. Moreover, specific feedback was given, which indicated the success of a
      response, or, in case of a mistake, indicated the type of error made. The task
      was presented in two phases: training and experimental. In the first phase, the
      child practised until a learning criterion was reached. In the experimental
      phase, four conditions were defined according to the information provided to the
      children. In general, the results of the training phase showed an improvement in
      performance with advancing age. Significant differences were found in children
      between 7 and 8 years of age, which points to an important transition period.
      Results of the experimental phase showed a pronounced impact of instructions on
      the performance of the task and on the strategies used to control timing
      behaviour. Specifically, the instructions that contained chronometric information
      caused an impairment in task performance and a change in the strategy used.

PMID- 15500809
TI  - Symmetry, averageness, and feature size in the facial attractiveness of women.
AB  - Female facial attractiveness was investigated by comparing the ratings made by
      male judges with the metric characteristics of female faces. Three kinds of
      facial characteristics were considered: facial symmetry, averageness, and size of
      individual features. The results suggested that female face attractiveness is
      greater when the face is symmetrical, is close to the average, and has certain
      features (e.g., large eyes, prominent cheekbones, thick lips, thin eyebrows, and
      a small nose and chin). Nevertheless, the detrimental effect of asymmetry appears
      to result solely from the fact that an asymmetrical face is a face that deviates
      from the norm. In addition, a factor analysis indicated that averageness best
      accounts for female attractiveness, but certain specific features can also be
      enhancing.

PMID- 15500811
TI  - Is there evidence that cognitive behaviour therapy is an effective treatment for
      schizophrenia? A cautious or cautionary tale?
AB  - Schizophrenia is a severe and disabling disorder with considerable psychological,
      social and economic costs. Over the last 15 years there has been a significant
      development in the use of cognitive behaviour therapy for psychosis (CBTp) in the
      treatment of schizophrenia, with 20 randomised controlled trials having been
      published. The majority of this work has been with alleviating medication
      resistant symptoms in chronic patients, but preliminary work has also been
      carried out with speeding recovery in acute schizophrenia and in relapse
      prevention and early intervention. A review of these studies indicates modest
      effect sizes, with the strongest evidence available for chronic patients. There
      is evidence that the effect size of the trials is significantly and negatively
      correlated to their methodological quality. We conclude cautiously that overall
      there is good evidence for the efficacy and effectiveness of CBTp in the
      treatment of schizophrenia.

PMID- 15500810
TI  - The contributions of egocentric and allocentric reference frames in haptic
      spatial tasks.
AB  - The influence of egocentric and allocentric reference frames on performance in
      haptic spatial tasks, was tested in three conditions. Blindfolded subjects had to
      make two bars haptically parallel, perpendicular or mirrored in the midsagittal
      plane. The hypothesis is that the contributions of egocentric and allocentric
      reference frames are combined, resulting in settings that lie in between the allo
      representation and the ego-representation. This leads to different predictions
      for the outcome of different conditions. All findings were consistent with the
      hypothesis. In addition, for subjects with large deviations a reversal of the
      oblique effect was found once again, which provides extra support for the
      hypothesis.

PMID- 15500812
TI  - An investigation of monitoring for sleep-related threat in primary insomnia.
AB  - In Study 1, individuals with primary insomnia (n=32) and good sleepers (n=38),
      recruited from a university population, completed a semi-structured interview.
      The interview assessed monitoring for sleep-related threat, negative thoughts and
      safety behaviours, at night and during the day. Compared to good sleepers,
      individuals with insomnia reported more frequent monitoring at night and during
      the day, more negative thoughts associated with monitoring at night and during
      the day, and the use of more safety behaviours associated with monitoring at
      night. A path analysis showed that the total monitoring frequency was
      significantly positively related to the score for total negative thoughts, which
      in turn, was significantly positively related to the total number of safety
      behaviours used. Study 2 aimed to test the generalisability of these findings in
      a clinical sample of individuals with primary insomnia (n=23). The results
      indicated that the clinical sample also engaged in monitoring for sleep-related
      threat, experienced negative thoughts and used safety behaviours. Further, more
      severe insomnia was associated with more negative thoughts and the use of more
      safety behaviours associated with monitoring at night. Together, these results
      are consistent with the proposal that monitoring for sleep-related threat
      functions to maintain insomnia by triggering negative thoughts and the use of
      safety behaviours. Future research is required to verify the proposed causal
      status of monitoring, using prospective designs and experimental manipulations.

PMID- 15500813
TI  - An animal model of fetishism.
AB  - An animal model of sexual fetishism was developed with male Japanese quail based
      on persistence of conditioned sexual responding during extinction to an inanimate
      object made of terrycloth (Experiments 1 and 3). This persistent responding
      occurred only in subjects that came to copulate with the terrycloth object,
      suggesting that the copulatory behavior served to maintain the fetishistic
      behavior. Sexual conditioning was carried out by pairing a conditioned stimulus
      (CS) with the opportunity to copulate with a female (the unconditioned stimulus
      or US). Copulation with the CS object and persistent responding did not develop
      if the CS was a light (Experiment 1) or if conditioning was carried out with a
      food US (Experiment 2). In addition, subjects that showed persistence in
      responding to the terrycloth CS did not persist in their responding to a light CS
      (Experiment 3). The results are consistent with the hypothesis that conditioned
      copulatory behavior creates a form of self-maintenance that leads to persistent
      responding to an inanimate object. The development of an animal model of such
      fetishistic behavior should facilitate experimental analysis of the phenomenon.

PMID- 15500814
TI  - I might look OK, but I'm still doubtful, anxious, and avoidant: the mixed effects
      of enhanced video feedback on social anxiety symptoms.
AB  - Previous experiments suggest that cognitive preparation for video feedback
      enhances its effects. In the current experiment, which included 95 speech-anxious
      undergraduates, these effects were more fully assessed, including those on self
      perception, anxiety, and speech-avoidance behavior, with an attention-control
      preparation as a comparison condition. A possible mechanism of the cognitive
      preparation's effects, moderation of the effects of self-observer discrepancy,
      was also tested. Results indicated that the cognitive preparation showed strong
      effects in regard to self-perception of performance, weak effects in anxiety
      reduction, and null effects in behavior. Consistent with previous research, self
      observer discrepancy showed a robust tendency to predict participant response
      across conditions.

PMID- 15500815
TI  - The relationship between miscellaneous symptoms and major symptom factors in
      obsessive-compulsive disorder.
AB  - The diverse symptomatology of obsessive-compulsive disorder (OCD) is being
      increasingly regarded as reducible to a few symptom dimensions. However,
      prevailing factor-analytically derived models of symptom structure omit a number
      of the well-recognized "miscellaneous" symptoms of OCD. This study sought to
      determine whether miscellaneous OCD symptoms, ascertained by the Yale-Brown
      Obsessive-Compulsive Scale symptom checklist, could be differentially and
      reliably predicted by four symptom factors (obsessions and checking, symmetry and
      ordering, contamination and cleaning, and hoarding) in two independent groups of
      individuals with OCD (n=381 and n=107). Logistic regression analyses were used to
      determine the association of each of the miscellaneous symptoms with the symptom
      factors; then a single confirmatory factor analysis was conducted to test the
      model of associations in the smaller sample. Sixteen (89%) of the 18 symptoms
      examined were reliably predicted by one (11 items) or two (5 items) of the
      factors, with obsessions and checking and symmetry and ordering emerging as
      foremost predictors. The expanded four-factor model showed good fit with data
      from the second sample. Results are conceptually meaningful, but suggest the
      inadequacy of groupings based solely upon overt behaviors. These findings may aid
      clinical understanding of OCD and be of value to studies using symptom factors to
      guide investigation of its causes and correlates.

PMID- 15500816
TI  - Experience and appraisal of worry among high worriers with and without
      generalized anxiety disorder.
AB  - Recent research has revealed that a large number of highly worried individuals do
      not qualify for a diagnosis of generalized anxiety disorder (GAD). This raises
      the intriguing question of why some high worriers are more impaired and
      distressed by their worrying than others, particularly when the severity of their
      worry is the same. The present investigation sought to address this question by
      examining whether GAD and non-GAD high worriers differ in their actual worry
      experiences, their subjective appraisals of worry experiences, or both
      experiences and appraisals of worry. GAD and non-GAD worriers, selected for
      matching levels of trait worry severity, completed an attention-focus task with
      thought sampling before and after a brief worry induction. They also completed
      questionnaires assessing their experiences during and after the worry induction,
      as well as their general beliefs about worry. GAD worriers experienced less
      control over negative intrusive thoughts immediately after worrying, reported
      greater somatic hyperarousal following worry, and endorsed several negative
      beliefs about worry more strongly than their worry-matched controls. Results
      suggest that GAD is associated with unique experiences and appraisals that
      distinguish it from other forms of severe worry.

PMID- 15500817
TI  - Comparison of behavioral and cognitive-behavioral one-session exposure treatments
      for small animal phobias.
AB  - This study evaluated the efficacy of behavioral and cognitive-behavioral one
      session exposure treatment procedures with and without programmed generalization
      for participants with small animal phobias. Forty participants were randomly
      assigned to the treatment and generalization conditions. Both treatments produced
      significant improvements from pre-test to post-test and these results were
      maintained for 1 year. The treatment effect sizes ranged from large to very large
      across behavioral, self-report, and subjectively rated measures. Participants in
      the behavioral treatment condition reported that the treatment was significantly
      more intrusive than participants in the cognitive-behavioral treatment group. The
      programmed generalization condition did not produce additional measured benefit.
      The results are discussed in terms of the overall effectiveness of one-session
      exposure treatment components for small animal phobias.

PMID- 15500818
TI  - Reliability, diagnostic efficiency, and validity of the Millon adolescent
      clinical inventory: examination of selected scales in psychiatrically
      hospitalized adolescents.
AB  - This study examined the internal consistency, diagnostic efficiency, and validity
      of selected scales of the Millon adolescent clinical inventory (MACI; Millon et
      al., Manual for the Millon Adolescent Clinical Inventory, National Computer
      Systems, Minneapolis, MN, 1993). 241 psychiatrically hospitalized adolescents
      were administered the MACI and a battery of established self-report measures and
      a multidisciplinary team independently assigned DSM-IV psychiatric diagnoses at
      the time of discharge. The internal consistency of MACI scales ranged from 0.71
      to 0.93. Conditional probabilities (sensitivity, specificity, positive predictive
      power, and negative predictive power) were calculated for selected disorders
      using independently generated clinical diagnoses as the standard. The diagnostic
      efficiencies for the selected scales were variable, with adequate performance for
      predicting classes of diagnoses but not for specific diagnoses. The MACI showed
      good criterion validity for most disorders, with participants with a clinical
      diagnosis having a significantly higher corresponding MACI scale score than
      participants not assigned that diagnosis. Concurrent validity, tested by
      correlating MACI scale scores with those of relevant, validated measures, was
      generally good. The MACI appears to be a psychometrically sound self-report
      instrument and appears valuable as a screening instrument for many problems found
      in adolescent psychiatric inpatients.

PMID- 15500819
TI  - Cataract formation in a strain of rats selected for high oxidative stress.
AB  - The primary purpose of this study was to define the clinical and morphological
      features of cataractogenesis in the OXYS strain of rats that generate excess
      reactive oxygen species. Rats were sequentially examined from birth to the
      development of mature cataracts with slit lamp biomicroscopy. Morphology of
      selected stages of cataract development was studied using light and transmission
      electron microscopy (TEM), immunohistochemical localization of the lipid
      peroxidation product 4-hydroxynonenal (HNE) and fluorescent antibody labeling for
      DNA oxidation products. Lenses from age-matched normal rats were used as
      controls. OXYS rats developed cataracts as young as two weeks of age with
      progression to maturity by 1 year. Clinically, cataracts appeared initially
      either as nuclear or sub-capsular cortical changes and progressed to pronounced
      nuclear cataracts within months. TEM confirmed the light microscopic impression
      of region-specific alterations in both fiber cell cytoplasmic protein matrix and
      membrane structure. The outer adult nuclear region showed extensive cellular
      damage similar to osmotic cataracts, which is consistent with the postulated high
      uptake of glucose in the OXYS strain. The adult and outer fetal nuclear cells
      displayed several types of focal damage. The inner fetal and embryonic nuclear
      cells demonstrated textured cytoplasm, suggesting protein degradation or
      redistribution. Staining for HNE was increased in epithelium, cortex and nucleus
      compared to control lenses. Fluorescent antibody probes demonstrated increased
      levels of DNA oxidation products in OXYS rat lenses compared to age-matched
      controls. Fourier analysis of nuclear cytoplasm revealed significant components
      with corresponding sizes greater than 100 nm and, using a new theoretical
      approach, the texturing of the cytoplasm was shown to be sufficient to cause
      opacification of the nucleus. The OXYS rat appears to be an ideal model for
      oxidative stress cataractogenesis. The potential oxidative damage observed is
      extensive and characteristic of the developmental region. The source of oxidative
      damage may in part be a response to elevated levels of glucose. Because oxidative
      stress is thought to be a major factor in cataract formation in both diabetic and
      non-diabetic aging humans, this animal model may be a useful tool in assessing
      efficacy of antioxidant treatments that may slow or prevent cataract formation.

PMID- 15500820
TI  - Tear film and ocular surface tests in animal models of dry eye: uses and
      limitations.
AB  - Many ocular surface tests have been developed for the clinical diagnosis of
      keratoconjunctivitis sicca, and several have been used to 'validate' animal
      models of Sjogren's and non-Sjogren's dry eye. However, many of these tests
      themselves have not been systematically studied or standardized, and yet their
      use in animal models of dry eye is common. This review provides a rational
      approach and systematic review of the tear film and ocular surface tests
      described in the literature that may be applicable to the current animal models
      of dry eye, with particular emphasis on their limitations, along with some
      suggestions regarding their standardization and applications in eye research.

PMID- 15500821
TI  - Variable oxygen and retinal VEGF levels: correlation with incidence and severity
      of pathology in a rat model of oxygen-induced retinopathy.
AB  - Retinal capillary quiescence is regulated by a delicate balance between
      proangiogenic and anti-angiogenic factors. Pathological angiogenesis is the
      result of a shift in this balance towards proangiogenic influences. Pathological
      angiogenesis is produced in a rat model of oxygen-induced retinopathy (OIR) by
      exposing newborn rat pups to alternating periods of hyperoxia and hypoxia. Based
      upon previous work, two similar exposure paradigms were investigated and
      compared, exposure of rat pups to alternating periods of 45 and 12.5% oxygen, and
      to alternating periods of 40 and 15% oxygen. The resulting retinal pathology was
      assessed by measurement of retinal clock hours with pathological blood vessel
      growth and the percentage of the retina that is avascular. The 45 and 12.5%
      exposure produced significantly greater incidence and severity of pathology than
      the 40 and 15% protocol. To explain the difference in pathology between these two
      very similar exposure protocols, retinal levels of proangiogenic vascular
      endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) and anti-angiogenic
      pigment epithelium-derived factor (PEDF) were measured by ELISA and western blot
      analysis at 0, 2, and 6 days post-exposure. In whole retinal lysates, there were
      no significant differences in VEGFR2 and PEDF levels. However, VEGF levels were
      approximately 48 and 78% higher on post-oxygen exposure day 0 and 2,
      respectively, in the group treated with alternating periods of 45 and 12.5%
      oxygen compared to the group treated with alternating periods of 40 and 15%
      oxygen. There was no significant difference in VEGF levels between these two
      groups on day 6 post-exposure. Therefore, the difference in pathology observed
      between these two experimental paradigms is associated with differences in whole
      retinal VEGF levels, but not changes in whole retinal VEGFR2 or PEDF levels. The
      results of this study suggest the existence of a threshold in the rat model of
      OIR, such that a small change in blood oxygen profile triggers a disproportionate
      increase in subsequent neovascularization, which is accompanied by more dramatic
      changes of retinal VEGF level than VEGFR2 or PEDF level. If a similar threshold
      exists for humans, it could explain why some oxygen-treated premature infants
      develop retinopathy and others do not, despite similar gestational ages, birth
      weights and clinical courses.

PMID- 15500822
TI  - Indocyanine green enhanced retinal vessel laser closure in rats: histologic and
      immunohistochemical observations.
AB  - PURPOSE: Feeder vessel photocoagulation using both thermal and indocyanine green
      (ICG) enhanced applications as a treatment for choroidal neovascularization is
      under investigation. While closure of feeder vessels is achievable, reperfusion
      of these vessels occurs. The purpose of the following study was to compare,
      contrast anatomic, and immunohistochemical findings in rat retinal arterioles
      following attempts at vessel closure using either the diode (810 nm) laser alone
      or in conjunction with intravascular ICG. METHODS: The retinal arterioles of
      adult Lewis or Brown Norway rats were treated with diode laser alone or
      immediately following intravenous injection with 75 mg ml(-1) ICG. Retinal vessel
      closure was determined by examination of retinal flatmounts following FITC
      dextran or rhodamine-dextran perfusion. Anatomic changes were examined by
      electron microscopy and quantitative cellular changes were measured by perfusion
      with Hoechst 33342 nuclear staining. Recruited macrophages were detected by ED1
      immunohistochemistry. RESULTS: Treatment with diode laser alone resulted in
      partial retinal arteriolar closure seen only in pigmented animals. The use of
      adjuvant ICG achieved complete vessel closure in albino animals with reperfusion
      seen in all vessels by 7 days. Electron microscopy revealed an intraluminal clot
      only in ICG-enhanced diode laser treated animals, but with accompanying
      endothelial and perivascular cellular damage. Immunohistochemistry of the site of
      retinal arteriolar closure revealed a large increase in perivascular cellularity
      with an apparent influx of ED1 positive cells. CONCLUSION: ICG-enhanced diode
      laser photocoagulation appears to be superior to diode treatment alone in
      achieving vessel closure, but is limited by clot resolution due to both excessive
      vascular damage and an accompanying inflammatory response. These results suggest
      that more durable feeder vessel closure rates may be achievable with either the
      use of accompanying anti-inflammatory therapies or with a less vascular damaging
      photoactivating dye.

PMID- 15500823
TI  - Expression of aminopeptidase B in the developing and adult rat retina.
AB  - Aminopeptidase B (Ap-B), a ubiquitous enzyme, catalyses the amino-terminal
      cleavage of basic residues of peptide or protein substrates, indicating a role in
      precursor processing. The physiological function of Ap-B still remains an open
      question, even though its activity suggests that it could be involved in
      inflammatory processes and proliferation of tumor cells. This study was conducted
      to determine the expression of Ap-B in the developing and adult retina as a path
      to envisage physiological roles of Ap-B. RT-PCR and in situ hybridization were
      used to detect expression of Ap-B mRNA and activity tests, Western blotting and
      immunofluorescence microscopy were performed to identify and localize the enzyme
      in the rat retina. These biochemical and morphological methods show that Ap-B is
      expressed in the retina from embryo to adult. Expression level is restricted to
      specific layers (pigmented epithelium, outer and inner plexiform layers and
      ganglion cell layer) and is developmentally regulated. Moreover, a preliminary
      analysis indicates that Ap-B, the glucose transporter GLUT3 and choline
      acetyltransferase (ChAT) share a similar expression pattern in retina.
      Altogether, Ap-B appears predominantly expressed in neuronal cells lying in
      retinal layers containing neuritic extensions and synaptic junctions. Such
      expression is up-regulated during ontogenesis allowing to hypothesized that Ap-B
      participates in processes accompanying retinal neuronal cell differentiation.

PMID- 15500824
TI  - Thrombospondin-1 in the trabecular meshwork: localization in normal and
      glaucomatous eyes, and induction by TGF-beta1 and dexamethasone in vitro.
AB  - Transforming growth factor-beta2 (TGF-beta2) is elevated in the aqueous humor of
      patients with primary open-angle glaucoma (POAG), and high levels of TGF-beta2
      are thought to contribute to the pathogenesis of POAG. Most TGF-beta2 in the eye
      is present in a latent, inactive form and the mechanisms of its in vivo
      activation are unclear. Since thrombospondin-1 (TSP-1) is one of the most potent
      in vivo activating molecules of TGF-betas, we investigated the localization and
      expression of TSP-1 in the aqueous humor outflow pathways. TSP-1
      immunohistochemistry was performed in the eyes of human donors (8 normal and 17
      with glaucoma). In addition, the eyes of Tsp-1(-/-)-deficient mice and normal Tsp
      1(+/+) mice were investigated. TSP-1 mRNA expression was assessed by reverse
      transcription-polymerase chain reaction and Northern blotting of RNA from fresh
      trabecular meshwork (TM), and human and mouse TM cells in vitro. In addition,
      Northern and Western blot analyses of TM cells after incubation with TGF-beta and
      dexamethasone were performed. In most of the eyes, TSP-1 immunolabeling was
      predominantly observed in extracellular areas of the juxtacanalicular
      (cribriform) part of the TM. Some focal staining was observed in the
      corneoscleral and uveal parts of the TM. In the eyes of six glaucoma patients
      (including one with steroid-induced glaucoma), TSP-1 immunoreactivity was
      considerably more intense and all regions of the TM were positively labeled. In
      double labeling experiments, staining for TSP-1 did not overlap with that of
      fibronectin or type VI collagen. mRNA for TSP-1 was detected in both fresh and
      cultured TM cells. Incubation of TM cells with TGF-beta1 and dexamethasone caused
      a marked increase in TSP-1 expression. TSP-1 in the TM might act as a potent
      local endogenous activator of TGF-betas in the aqueous humor and mediate any
      local effects of TGF-beta and/or dexamethasone on the outflow of aqueous humor.

PMID- 15500825
TI  - Altered traffic to the lysosome in an ex vivo lacrimal acinar cell model for
      chronic muscarinic receptor stimulation.
AB  - Evidence suggests that lacrimal and salivary epithelial cells constitutively
      expose potentially pathogenic autoantigens, but that active regulatory networks
      normally suppress pathological autoimmune responses . Events that potentially
      disrupt the regulatory networks include increased exposure of constitutive
      autoantigens and induced exposure of previously cryptic autoantigen epitopes.
      Chronic muscarinic receptor (MAChR) stimulation in an ex vivo rabbit lacrimal
      acinar cell model induces functional and biochemical alterations reminiscent of
      the functional quiescence associated with Sjogren's syndrome . Chronic MAChR
      stimulation also elicits changes in the compartmental distribution of beta
      hexosaminidase, a product that normally is dually targeted into the lysosomal
      pathway and the regulated apical secretory pathway. Here, we use subcellular
      fractionation analyses to further explore the nature of the stimulation-induced
      traffic changes and to identify effectors that might mediate this change.
      Overnight stimulation of primary cultured rabbit lacrimal gland acinar cells with
      10 microM carbachol (CCh) significantly decreased the abundance of mature
      cathepsin B in the pre-lysosome and lysosome; decreased the abundance of
      preprocathepsin B in fractions containing the TGN and late endosome; increased
      the abundance of procathepsin B in fractions containing the basal-lateral
      membrane; and increased the accumulation of endocytosed [(125)I]-EGF in the
      recycling endosome. Alterations in distribution or abundance of traffic effectors
      included: increased abundances of rab5A and rab6 in the TGN; decreased overall
      abundance of gamma-adaptin; remarkably increased relative abundance of membrane
      phase-associated actin; redistribution of cytoplasmic dynein from biosynthetic
      and proximal endocytic compartments to the lysosome; and redistribution of
      p150(Glued) from the lysosome to biosynthetic or proximal endocytic compartments.
      We conclude that chronic MAChR stimulation blocks traffic from the early endosome
      and the TGN to the lysosome, causing lysosomal proteins to reflux to the TGN,
      endosomes, and basal-lateral membrane. These traffic alterations may be mediated
      through action on one or more of the effectors noted.

PMID- 15500826
TI  - Growth factors in the anterior segment: role in tissue maintenance, wound healing
      and ocular pathology.
AB  - A number of growth factors and their associated receptors, including epidermal
      growth factor, transforming growth factor-beta, keratinocyte growth factor,
      hepatocyte growth factor, fibroblast growth factor and platelet-derived growth
      factor have been detected in the anterior segment of the eye. On binding to
      cellular receptors, these factors activate signalling cascades, which regulate
      functions including mitosis, differentiation, motility and apoptosis. Production
      of growth factors by corneal cells and their presence in the tear fluid and
      aqueous humour is essential for maintenance and renewal of normal tissue in the
      anterior eye and the prevention of undesirable immune or angiogenic reactions.
      Growth factors also play a vital role in corneal wound healing, mediating the
      proliferation of epithelial and stromal tissue and affecting the remodelling of
      the extracellular matrix (ECM). These functions depend on a complex interplay
      between growth factors of different types, the ECM, and regulatory mechanisms of
      the affected cells. Imbalances may lead to deficient wound healing and various
      ocular pathologies, including edema, neovascularization and glaucoma. Growth
      factors may be targeted in therapeutic ophthalmic applications, through exogenous
      application or selective inhibition, and may be used to elicit specific cellular
      responses to ophthalmic materials. A thorough understanding of the mechanism and
      function of growth factors and their actions in the complex environment of the
      anterior eye is required for these purposes. Growth factors, their function and
      mechanisms of action as well as the interplay between different growth factors
      based on recent in vitro and in vivo studies are presented.

PMID- 15500827
TI  - Fatty acid cytotoxicity to human lens epithelial cells.
AB  - Data obtained with the neutral red cytotoxicity assay reveal that human lens
      epithelial cells in culture are highly sensitive to low micromolar concentrations
      of unsaturated, cis-configured fatty acids in the following order: arachidonic
      acid>linolenic acid=linoleic acid=oleic acid, whereas the saturated fatty acids
      are much less effective. Though the cytotoxic effects of the unsaturated fatty
      acids could not be discerned from effects of their oxidation products, the fact
      that oleic acid is equally cytotoxic as linoleic acid or linolenic acid as well
      as previously reported findings with bovine lens epithelial cells support the
      idea that the unsaturated fatty acid molecules directly account for the
      cytotoxicity and not their products of lipid peroxidation. Bleb formation and
      cell retraction are early morphological signs of fatty acid-induced lens cell
      damage. These cellular alterations are accompanied by an aggregation of
      intermediate filaments in a first step, whereas the disorganization of
      microfilaments occurs at a later time and only at higher fatty acid
      concentrations. Measurements of protein-, RNA- and DNA-synthesis turned out to be
      much less sensitive parameters for the fatty acid-induced damage of lens cells.
      The uptake rate of linoleic acid by human lens cells is relatively high (4.35
      fmol sec(-1) per 1000 cells), 30 and 50% higher as compared with diploid human
      embryonal lung fibroblasts and chemically transformed mouse fibroblasts,
      respectively. Saturation kinetics in combination with competition between
      linoleic acid, oleic acid and palmitic acid on one hand and ineffectiveness of
      trypsin and DIDS treatment on the other hand hint at cytoplasmic fatty acid
      binding proteins as receptors with high binding affinity (5.55 micromol l(-1),
      calculated for the linoleic acid-albumin complex) to be involved in the fatty
      acid uptake in human lens cells. Cellular fatty acid uptake is mainly influenced
      by the albumin concentrations present in physiological solutions. Albumin
      determinations in aqueous humor from 177 cataract patients reveal an age
      dependent, statistically significant albumin rise with average values below 2
      micromol l(-1) up to the age of 40 years to about 4 micromol l(-1) at the age
      between 80 and 90 years with single values up to 10 micromol l(-1). Using
      physiological fatty acid mixtures it is demonstrated that fatty acid-induced lens
      cell damage is strongly increased by elevated albumin concentrations found in
      aqueous humor of the elderly, who already have cataracts. Free fatty acid induced
      lens cell damage as a possible cause for age-dependent cataracts as well as a
      molecular link between systemic diseases such as diabetes and cataract formation
      is discussed.

PMID- 15500828
TI  - Thy-1 distinguishes human corneal fibroblasts and myofibroblasts from
      keratocytes.
AB  - After corneal injury, keratocytes become activated and transform into repair
      phenotypes-corneal fibroblasts or myofibroblasts, however, these important cells
      are difficult to identify histologically, compromising studies of stromal wound
      healing. Recent studies indicate that expression of the cell surface protein, Thy
      1, is induced in fibroblast populations associated with wound healing and
      fibrosis in other tissues. We investigated whether keratocyte transformation to
      either repair-associated phenotype induced Thy-1 expression. Human corneal
      keratocytes were isolated by collagenase digestion. The cells were either
      processed immediately (i.e. freshly isolated keratocytes) or were cultured in the
      presence of 10% fetal bovine serum or transforming growth factor-beta to induce
      transformation to the corneal fibroblast and myofibroblast phenotypes,
      respectively. Thy-1 mRNA and protein expression by freshly isolated keratocytes
      and corneal fibroblasts were assessed by RT-PCR and Western blotting. mRNA also
      was extracted from the whole intact stroma and assessed by RT-PCR. Thy-1 was
      localised immunocytochemically in cultured human corneal fibroblasts,
      myofibroblasts, and in keratocytes in normal human corneal tissue sections. Thy-1
      mRNA and protein were detectable in cultured human corneal fibroblasts, but not
      freshly isolated keratocytes. Whole uninjured stroma showed no detectable Thy-1
      mRNA expression. Cultured human corneal fibroblasts and myofibroblasts both
      labelled for Thy-1, but keratocytes in the stroma of normal human cornea did not.
      We conclude that Thy-1 expression is induced by transformation of keratocytes to
      corneal fibroblasts and myofibroblasts, suggesting a potential functional role
      for Thy-1 in stromal wound healing and providing a surface marker to distinguish
      the normal keratocyte from its repair phenotypes.

PMID- 15500829
TI  - Regional mapping of molecular components of human liquid vitreous by dynamic
      light scattering.
AB  - The distribution of particle sizes was studied in six regions of human liquid
      vitreous samples. Particle sizes were calculated from dynamic light scattering
      measurements as hydrodynamic diameter of molecules. In general, particle sizes
      increased progressively from anterior (near lens) to posterior (near retina). A
      much weaker trend of increase in particle size was found from nasal to temporal
      regions. Relative concentrations of particles of certain sizes were calculated
      from dynamic light scattering parameters. Viscosity coefficients of liquid
      vitreous samples were measured in a semi-micro viscometer. Hyaluronan
      concentrations increased from anterior to posterior and the reverse was true for
      viscosity, implying that the lower concentration of hyaluronan near the lens was
      offset by increased molecular size. A similar concentration gradient was found
      with the 6 nm diameter particles, and to a lesser degree with the 15 nm
      particles. The identities of these proteins must be resolved by techniques of
      proteomics.

PMID- 15500830
TI  - Emmetropisation under continuous but non-constant light in chicks.
AB  - It has been suggested that ambient lighting at night influences eye growth and
      might play a causal role in human myopia. To test this hypothesis, we reared
      newly hatched chicks under 12 hr light-dark or light-dim cycles with a light
      phase intensity of 1500 microW/cm(2) and variable dim phase intensities between
      0.01 and 500 microW/cm(2). Other chicks were reared under constant light
      conditions with intensities between 1 and 1500 microW/cm(2). After three weeks,
      the chicks were examined by refractometry, ultrasound and caliper measurements of
      enucleated eyes. To relate ocular parameters with a retinal neurotransmitter
      likely involved in eye growth control, retinal and vitreal levels of dopamine and
      its principal metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), were measured
      by high performance liquid chromatography with electrochemical detection in the
      light, dark and dim phases. Diurnal fluctuations in axial length and choroidal
      thickness also were measured twice daily by partial coherence interferometry
      (PCI) in chicks under light-dark and the two brightest light-dim conditions. The
      eyes of chicks reared under most light-dim conditions had refractions and ocular
      dimensions comparable to those reared under light-dark conditions. At dim phase
      light intensities of 10 microW/cm(2) and above, the day-night changes in retinal
      dopamine metabolism were not observed. The daily fluctuations of axial length and
      choroidal thickness were altered with rearing under the two brightest dim light
      intensities, compared to the light-dark condition. Rearing under constant light
      with intensities ranging between 1 and 1500 microW/cm(2) produced a shallow
      anterior chamber and other eye alterations previously described for constant
      light rearing even though rearing under continuous light that fluctuated between
      these same intensities generally permitted normal eye growth. Thus, continuous
      but fluctuating light exerts different developmental effects on the eye than
      constant non-fluctuating light. Light-dim rearing may be more relevant to daily
      human light exposures than other laboratory lighting conditions and may provide
      an opportunity to study developmental interactions of visual quality (e.g. blur,
      defocus, etc.) and features of the light-dark cycle under conditions that perturb
      daily rhythms in dopamine metabolism and ocular dimensions. Such studies also
      could provide mechanistic insights into whether and how daily rhythms in retinal
      dopamine metabolism, axial length or choroidal thickness modulate refractive
      development.

PMID- 15500832
TI  - Immunopathology of Chlamydophila abortus infection in sheep and mice.
AB  - Chlamydophila abortus targets the placenta, causing tissue damage, inflammation
      and abortion (enzootic abortion of ewes). It is one of the main infectious causes
      of abortion in ewes, resulting in major economic losses to agricultural
      industries worldwide. Although ruminants and pigs are the principal hosts, humans
      are also susceptible to infection. Control of disease requires a host
      inflammatory response, which is likely to contribute to pathology and abortion.
      Mouse models have been widely used to provide insight into the role of specific
      immune cells in controlling infection and disease. The use of such model systems
      for investigating the mechanisms of abortion, latency, persistence, and immunity
      to reinfection will result in the identification of novel vaccine control
      strategies for sheep.

PMID- 15500831
TI  - Effects of adenosine on optic nerve head circulation in rabbits.
AB  - This study was performed to determine whether intravitreal or intravenous
      adenosine can alter the microcirculation in the optic nerve head (ONH) of
      rabbits. Capillary blood flow in the ONH was measured serially with a laser
      speckle tissue analyser for 2 hr after the intravitreal (0.1, 1.0 and 10 nmol) or
      intravenous (0.2 and 0.6 mg kg(-1)min) injections of adenosine. In addition, the
      effect of specific adenosine A(1) and A(2a) antagonists and an adenosine
      triphosphate (ATP)-sensitive potassium (K(ATP)) channel blockers on the adenosine
      induced changes on the ONH blood flow was analysed. Intravitreal adenosine
      increased the capillary blood flow in the ONH in a dose-dependent manner, while
      intravenous adenosine had no effect. Co-administration of the specific adenosine
      A(1) receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 10 nmol)
      significantly suppressed (P=0.006, ANOVA) the increase in the ONH blood flow
      induced by adenosine (10 nmol). The specific A(2a) receptor antagonist, 8-(3
      chlorostyryl) caffeine (CSC, 10 nmol), had a weak effect in inhibiting the
      increase but the change was not significant (P=0.08, ANOVA). Both specific A(1)
      and A(2a) receptor agonists, N(6)-cyclopentyladenosine (CPA, 10 nmol) and 2-p-(2
      carboxyethyl) phenethyl-amino-5'-N-ethylcarboxamidoadenosine (CGS-21680, 10
      nmol), increased the ONH tissue blood flow (P<0.01, ANOVA). Glibenclamide (10
      nmol), a selective K(ATP) channels antagonist, suppressed the increase of ONH
      blood flow induced by 10 nmol adenosine significantly (P<0.001, ANOVA). On the
      other hand, 10 nmol of 8-Br-cAMP, a cAMP analog, failed to enhance the capillary
      blood flow in the ONH. These results indicate that adenosine increases the
      capillary blood flow in the ONH of rabbits, and it acts through A(1) and A(2a)
      receptors from the ablumenal side where pericytes are located. Activation of
      K(ATP) channels is strongly related to the mechanism of adenosine-induced
      increase in ONH blood flow, while the participation of adenylate cyclase is less
      likely.

PMID- 15500833
TI  - Nasal and frontal sinus mucosa of the adult dog contain numerous olfactory
      sensory neurons and ensheathing glia.
AB  - Olfactory glial cells have been the focus of much recent research interest
      because of their possible future use as cellular transplants in repair of spinal
      cord injury. Although olfactory glial cells can be collected from the olfactory
      bulb for in vitro culture, alternative sites would be preferable for safer
      surgical access. This study was designed to investigate the distribution of
      olfactory sensory neurons and olfactory glial cells within the canine peripheral
      olfactory system. Using immunohistochemistry and electron microscopy on perfused
      tissue we demonstrate that olfactory sensory neurons are found in both the caudal
      nasal and the frontal sinus epithelia. Olfactory ensheathing glia were found in
      the mucosa at both these sites implying that surgical access for harvesting cells
      for transplantation would be straightforward.

PMID- 15500834
TI  - Biochemical markers of bone turnover in the dairy cow during lactation and the
      dry period.
AB  - We measured a bone-formation marker recognizing osteocalcin, and a bone
      resorption marker recognizing C-telopeptide (CT(x)) fragments of collagen type I,
      in a longitudinal study. The levels of these markers in the plasma of dairy cows
      (n=11) were recorded over a 12 month postpartum period, including a full
      lactation and a dry period. The plasma concentration of CT(x) was highest in the
      first week after parturition. It then declined slowly over the next 33 weeks and
      remained low until the next parturition. Osteocalcin concentration was lowest
      around parturition, reached a plateau during mid-lactation, then fell again
      towards term. There were large variations in bone metabolism during a lactation,
      that were not directly related to milk production. These results may be used to
      facilitate appropriate adjustments to calcium and phosphorous concentrations in
      the diet, reflecting the specific needs of each stage of the reproductive cycle.

PMID- 15500835
TI  - Activities of enzymes in some types of peripheral leucocytes may reflect the
      differences in nutrient metabolism between dogs and cats.
AB  - Plasma metabolites and immunoreactive insulin (IRI) concentrations and enzyme
      activities of some types of peripheral leucocytes were measured to clarify one
      aspect of the differences in nutrient metabolism between dogs and cats. There
      were no significant differences in plasma concentrations of glucose,
      triglyceride, free fatty acids and IRI between dogs and cats. Higher total
      cholesterol and lower HDL cholesterol concentrations were observed in feline
      plasma, and H/T ratio (HDL/total cholesterol concentrations) was significantly
      lower than that in canine plasma. The cytosolic activities of fructokinase (FK),
      pyruvate kinase (PK), glucose-6-phosphate dehydrogenase (G6PD) and lactate
      dehydrogenase (LDH) were significantly higher and the activities of cytosolic
      malate dehydrogenase (MDH) and mitochondrial glutamate dehydrogenase (GLDH) were
      significantly lower in feline leucocytes than those in canine leucocytes. Higher
      activities of FK, PK and G6PD, which regulate the rate of biosynthesis of fatty
      acids, may reflect the different characteristics in nutrient metabolism in feline
      tissues from canine tissues.

PMID- 15500836
TI  - Evaluation of pressor sensitivity to norepinephrine infusion in dogs with
      iatrogenic hyperadrenocorticism. Pressor sensitivity in dogs with
      hyperadrenocorticism.
AB  - Hypertension is a common complication of canine hyperadrenocorticism. Increased
      pressor sensitivity to endogenous catecholamines is currently believed to be the
      main mechanism involved in the development of hypertension in human
      hyperadrenocorticism. The aim of this study was to evaluate pressor sensitivity
      to norepinephrine in dogs after induction of iatrogenic hyperadrenocorticism (I
      HAC) by serial arterial blood pressure measurements during infusions of
      increasing dose rates of norepinephrine (0.1, 0.15, 0.2, 0.3, 0.4, 0.6, and 0.8
      microg/kg/min) in eight dogs with I-HAC and eight control dogs. Systolic,
      diastolic, mean blood pressure and heart rate measurements were recorded. The
      changes in these parameters between the two groups of dogs were compared. Dogs in
      the I-HAC group had a more pronounced pressor response to norepinephrine
      infusions than control dogs since the infusions had to be stopped in seven of the
      dogs due to severe hypertension (>240 mmHg). The mean maximum tolerated dose rate
      in the control group was 0.6 microg/kg/min with a standard error of 0.0 and 0.34
      microg/kg/min with a standard error of 0.08 in the I-HAC group. The study
      demonstrated the presence of increased pressor sensitivity to norepinephrine in
      dogs with I-HAC.

PMID- 15500837
TI  - Antimicrobial susceptibility of Enterococcus strains isolated from poultry
      faeces.
AB  - We have investigated the resistance of Enterococcus isolated from poultry faeces
      to antibiotics commonly used as therapy of enterococcal infections.
      Identification was made by the method of Facklam and Collins. Minimal inhibitory
      concentrations of penicillin, ampicillin, vancomycin and teicoplanin were
      determined and high level aminoglycoside resistance was investigated. Genes
      codifying high level aminoglycoside resistance (HLAR) were determined by PCR.
      Fifty five Enterococcus strains were isolated (63.6% E. faecalis, 12.7% E.
      mundtii, 9.1% E. faecium, 7.3% E. casseliflavus, 3.7% E. durans and 3.6% E.
      hirae). None of the strains were resistant to VAN, TEC, P or AM. HLAR was found
      in 34.5% of strains for SM, 27.3% for KM and 7.3% for GM. The gene for the
      bifunctional enzyme was found only in one strain, that showed HLAR to GM and KM.
      Fourteen strains harboured the gene aph(3')-III, being 11 resistant to KM and
      STR, and three resistant to GM, KM and STR. The remaining six strains showed HLAR
      to STR, but were negative for the three genes tested by PCR. The gene ant(4'4")
      was not detected in any of the strains. No unexpected vancomycin resistance was
      detected. The resistance rates among poultry strains were lower than those found
      among human strains isolated from hospital patients in recent Canary studies.

PMID- 15500839
TI  - Teat onchocercosis in cows with reference to prevalence, species involved and
      pathology.
AB  - The present study reports teat onchocercosis in cows in the province of Kars in
      north eastern Turkey with reference to the prevalence, species involved and
      pathological findings. In the study, 600 cows of various breeds and ages
      slaughtered in the local abattoir were examined and 145 (24%) were found to have
      various lesions on their teats, of which 45 (31%) were infected with three
      Onchocerca species (Onchocerca gutturosa, O. lienalis and an unidentified
      Onchocerca spp.), identified according to their morphological characteristics.
      Gross pathological examination of the teats with lesions revealed scabies and
      chaps of varying sizes, healed sores and small nodules. Histopathologically,
      large numbers of microfilariae were commonly observed within the collagenous
      fibre bundles of the dermis, with only a few microfilariae in the dermis in some
      cases. The microfilariae were also often found to have accumulated around the
      perivascular spaces and were frequently associated with infiltration by
      inflammatory cells, predominantly eosinophil leukocytes and mononuclear cells. In
      two cases, microfilariae were discovered exclusively in the lumen of the
      capillaries of the dermal papillaries. In one case, in which microfilarae were
      not encountered, sections of adult worms surrounded by neutrophil leukocytes were
      detected free in the teat canal. The presence of extensive teat lesions along
      with microfilariae of the Onchocerca species as found in this study warrants
      further assessment of the impact of onchocercosis on dairy farming.

PMID- 15500838
TI  - Malate dehydrogenase activities are lower in some types of peripheral leucocytes
      of dogs and cats with type 1 diabetes mellitus.
AB  - The activities of the enzymes in the malate-aspartate shuttle were measured in
      peripheral leucocytes of spontaneous type 1 diabetic dogs and cats treated with
      insulin injections. In the diabetic dogs and cats, fasting plasma glucose
      concentrations were three- or fourfold greater than the control levels in spite
      of insulin injections and the activities of cytosolic malate dehydrogenase (MDH),
      one of pivotal enzymes in the malate-aspartate shuttle, were remarkably lower
      than the controls. Depressed expression of cytosolic MDH mRNA was confirmed by RT
      PCR analysis in the diabetic animals. The cytosolic ratio of MDH/lactate
      dehydrogenase (LDH) activity (M / L ratio) in leucocytes of the diabetic animals
      was significantly lower than that of normal control animals. The smaller M / L
      ratio appeared to reflect depression of energy metabolism in the diabetic
      animals. Intrinsically lower and further decreased MDH activities may be factors
      that induce insulin resistance observed in diabetic cats.

PMID- 15500840
TI  - Mammary cell turnover in lactating ewes is modulated by changes of energy fuels.
AB  - The study of cell turnover of mammary gland helps to gain understanding of the
      subtle modulation that largely determines milk production. To evaluate the effect
      of diet composition on cell turnover of mammary gland, pluriparous sheep were
      allotted to three experimental groups and fed from day 33 after lambing a control
      diet (BD), a high starch (HS) diet or a high fat (HF) diet. Biopsies of mammary
      gland tissue were collected at 50 days after lambing for in situ detection of
      cell death and RT-PCR analysis of bax, bcl-2, caspase-3 and GST expressions. Both
      apoptotic and proliferation indexes were significantly higher (P<0.05) in the BD
      group compared to HS and HF groups. The relative expressions of GST were
      significantly greater (P<0.05) in HF group compared to the BD and HS groups.
      There was a significant increase in the ratio of bcl-2 to bax mRNA in the HS and
      HF groups. Availability of energy substrates for mammary gland can interfere with
      the cell fate, modulating genes involved in the control of oxidative stress
      which, in turn, can indirectly regulate cell apoptosis and proliferation.

PMID- 15500841
TI  - Evaluation of pathological changes in broilers during chronic aflatoxin (50 and
      100 ppb) and clinoptilolite exposure.
AB  - This study was conducted to evaluate the pathological changes in broilers fed a
      diet containing low-levels of aflatoxin (AF) and clinoptilolite (CLI) until 42
      days of age. A total of 576 one-day-old Ross-308 type broiler chicks were treated
      with varying levels of AF and CLI (15 g kg(-1)). The gross and histopathological
      changes in the liver, kidneys, spleen, thymus and bursa of Fabricius were
      investigated and relative organ weights were calculated. Compared to controls,
      significant changes (P<0.05), such as slight to moderate hydropic degeneration
      and/or fatty change (8 cases of 10), bile-duct hyperplasia (7 of 10) and
      periportal fibrosis (5 of 10), were found in chicks fed 100 ppb AF-containing
      diet. No gross-pathological changes were observed in any treatments. The addition
      of CLI to the 100 ppb AF-containing diet significantly decreased the number of
      affected broilers and/or the severity of lesions (hydropic degeneration and bile
      duct hyperplasia) in the livers (P<0.05). The addition of CLI to the AF-free diet
      did not produce any significant lesions compared with the controls.

PMID- 15500842
TI  - Effects of non-steroidal anti-inflammatory drugs on pain-related behaviour in a
      model of articular pain in the domestic fowl.
AB  - The optimum doses of carprofen, flunixin, ketoprofen and sodium salicylate for
      the treatment of inflammatory pain were determined in domestic fowl using the
      microcrystalline sodium urate model of articular pain. The response criteria were
      the changes in pain-related behaviour over 60 min commencing 1 h after an intra
      articular injection of sodium urate and an intramuscular injection of a range of
      doses of each of the drugs. The minimum effective doses for carprofen, flunixin
      and ketoprofen, respectively, were 30, 3 and 12 mg kg(-1). The minimum dose for
      sodium salicylate ranged from 100 to 200 mg kg(-1) and did not fully restore
      normal behaviour.

PMID- 15500843
TI  - Isopathic and pluralist homeopathic treatment of commercial broilers with
      experimentally induced colibacillosis.
AB  - This study sought to determine the efficacy of isopathic and pluralist
      homeopathic treatment of colibacillosis in broiler chickens and thereby
      contribute to the evaluation of homeopathy in general. In each of two experiments
      three groups of broilers, infected intratracheally at 8 days of age with E. coli
      (O78:K80), were treated with different combinations of homeopathic remedies.
      Control groups and an infected, doxycyline-treated group were included.
      Experiments differed only in the dose of E. coli. Efficacy of treatment was
      evaluated based on the parameters mortality, body weight gain and colibacillosis
      lesions. In both experiments doxycyline prevented mortality and reduced E. coli
      lesions and stunting. None of the homeopathically treated groups differed
      significantly with respect to any of the parameters from the non-medicated,
      infected control group. It is concluded that the results of this study do not
      justify use of these homeopathic remedies for treatment of colibacillosis in
      broilers. Furthermore, no significant effects of this homeopathic treatment were
      established.

PMID- 15500844
TI  - Circadian and seasonal variability and influence of sex and race on eight
      clinical chemistry parameters in budgerigars (Melopsittacus undulatus, Shaw
      1805).
AB  - The aim of the study was to investigate if there is a clinically relevant
      influence of daytime or season and if there are sex-dependant differences in some
      frequently determined clinical chemistry parameters. The study was performed with
      99 1.5- to 2-year old healthy budgerigars of three races. A harmonic regression
      analysis was performed taking into account linear and cyclic trends over the
      year. Correlations were investigated by the calculation of Spearman correlation
      coefficients. Summarizing, it can be said that some circadian, seasonal, as well
      as sex- and race-dependant influences have been shown. However, although the
      differences are statistically significant, they were too small to have an impact
      on clinical decision making. As clinical chemistry results are in practice
      independent from the influence factors investigated, their meaning and use as a
      diagnostic tool is further substantiated.

PMID- 15500845
TI  - Electroejaculation in the Chinchilla (Chinchilla lanigera): effects of anesthesia
      on seminal characteristics.
AB  - Repetitive electroejaculation is probably extremely stressful in conscious
      animals and could adversely affect fertility. The present study was designed to
      (a) evaluate the effects of anesthesia (40 mg ketamine/kg body weight, i.m.) on a
      method of electroejaculation used previously in conscious chinchillas (Chinchilla
      lanigera), and (b) determine the quality of the electroejaculated semen obtained
      under anesthesia. In Experiment 1 (8 animals), a 4 x 4 Latin square design was
      used to study the effects of anesthesia and ejaculatory voltage on semen
      collection, ejaculate volume, sperm concentration, motility, viability, response
      to the hypoosmotic swelling test (HOST), and acrosomal status. In Experiment 2
      (12 animals), the effects of differing voltages and the number of stimuli on
      ejaculation by conscious or anesthetized males was determined. In both
      experiments, all the conscious animals ejaculated, but only 60% ejaculated under
      anesthesia and they required more stimuli and higher voltages to achieve
      ejaculation. Ejaculate volume was significantly lower in anesthetized (<5 microl)
      than in conscious animals (>40 microl), but sperm concentration was unaffected.
      None of the indices of sperm quality were affected by anesthesia. The techniques
      we have developed in anesthetized domestic chinchillas should be applicable to
      endangered chinchillas in the wild, and though the number of sperm available is
      reduced, there are still sufficient for assisted reproduction.

PMID- 15500846
TI  - Brown spiders and loxoscelism.
AB  - Accidents caused by brown spiders (Loxosceles genus) are classically associated
      with dermonecrotic lesions and systemic manifestations including intravascular
      haemolysis, disseminated intravascular coagulation and acute renal failure.
      Systemic reactions occur in a minority of cases, but may be severe in some
      patients and occasionally fatal. The mechanisms by which Loxosceles venom exerts
      these noxious effects are currently under investigation. The venom contains
      several toxins, some of which have been well-characterised biochemically and
      biologically. The purpose of the present review is to describe some insights into
      loxoscelism obtained over the last ten years. The biology and epidemiology of the
      brown spider, the histopathology of envenomation and the immunogenicity of
      Loxosceles venom are reviewed, as are the clinical features, diagnosis and
      therapy of brown spider bites. The identification and characterisation of some
      toxins and the mechanism of induction of local and systemic lesions caused by
      brown spider venom are also discussed. Finally, the biotechnological application
      of some venom toxins are covered.

PMID- 15500847
TI  - Amino acid sequence of a thrombin like enzyme, elegaxobin II, from the venom of
      Trimeresurus elegans (Sakishima-Habu).
AB  - The amino acid sequence of a thrombin like enzyme , named elegaxobin II, isolated
      from the venom of Trimeresurus elegans (Sakishima-habu) was determined by Edman
      sequencing of the peptides which was derived from digests with cyanogen bromide,
      achromobacter protease I, trypsin, endoproteinase Asp-N, and chymotrypsin.
      Elegaxobin II consisted of 233 amino acids and showed conservation of the
      catalytic amino acid residues (His(57), Asp(102), and Ser(195)) of chymotrypsin
      family serine protease in its amino acid sequence. The carboxyterminal amino
      acid, Leu, was determined using carboxypeptidase Y. This enzyme contains
      glucosamine and an N-linked glycosylation site. Elegaxobin II was 91% homologous
      in sequence to elegaxobin and protease I from the same snake venom, and it was
      67, 75, 31 and 26% homologous in sequences to flavoxobin, KN-BJ 2, human
      kallikrein and bovine thrombin, respectively. Elegaxobin II lacked thrombin's ETW
      (146-148) loop, as well as its functionally important YPPW (60-insertion loop).

PMID- 15500848
TI  - Protective efficacy and the recovery profile of certain chemoprotectants against
      lethal poisoning by microcystin-LR in mice.
AB  - The cyclic peptide toxins microcystins and nodularins are the most common and
      abundant cyanotoxins present in diverse water systems. They have been the cause
      of human and animal health hazards and even death. Development of suitable
      chemoprotectants against microcystin is essential considering the human health
      importance. In the present study, three agents cyclosporin-A (10mg/kg), rifampin
      (25mg/kg) and silymarin (400mg/kg) pre-treatment gave 100% protection against
      lethal dose of microcystin-LR (100 microg/kg). Various biochemical parameters
      were evaluated to study the recovery profile of protected animals at 1, 3, 7 and
      14 days post-toxin treatment. There was significant depletion of hepatic
      glutathione in protected animals compared to control group till 7 days post
      treatment but normalised by 14 days. Similarly enhanced hepatic lipid
      peroxidation, inhibition of protein phosphatase activity was observed till 3-7
      days post-treatment in protected animals. Elevated levels of enzymes alanine
      amino transferase, lactate dehydrogenase and sorbitol dehydrogenase were observed
      in serum at 1 day post-treatment. All the biochemical variables reached control
      levels by 14 day post-treatment. Immunoblotting analyses of liver homogenates
      showed microcystin-protein phosphatase adduct in liver samples of toxin treated
      as well as antidote-protected animals. The adduct could be seen even after 14
      days post-toxin treatment. The study shows that though cyclosporin-A, rifampin
      and silymarin could offer 100% protection against microcystin-LR induced
      lethality many of the toxic manifestations are persistent and could not be
      reversed till 7 days.

PMID- 15500849
TI  - Modelling Tityus scorpion venom and antivenom pharmacokinetics. Evidence of
      active immunoglobulin G's F(ab')2 extrusion mechanism from blood to tissues.
AB  - Modelling Tityus scorpion venom and antivenom pharmacokinetics. Evidence of
      active immunoglobulin G's F(ab')(2) extrusion mechanism from blood to tissues. We
      measured pharmacokinetic parameters for T. discrepans venom in rams. Forty, 75 or
      100 microg/kg venom were injected subcutaneously in the inner side of the thigh.
      Plasma venom content (venenemia) was determined by enzyme-linked immunosorbent
      assay (ELISA) from 0 to 300 min after injecting venom. Venenemia was fit to a
      three-compartment model (inoculation site, plasma and extra vascular
      extracellular space), it was assumed that the venom may also be irreversibly
      removed from plasma. Calculated time course of venom content shows that at any
      time no more that 30% of the venom is present in plasma. Venenemia peaks at 1h
      and decays afterwards. Fluorescently labelled antivenom [horse anti
      TityusF(ab')(2) or fraction antigen binding, immuglobulin without Fc chain
      covalently bound to fluorescine or fluorescamine] pharmacokinetics was
      determined. Although F(ab')(2) molecular weight is >/=10 times bigger that
      toxin's, the rate of outflow of F(ab')(2) from blood to tissues was approximately
      4 times faster than the venom's outflow. Venom content in the injection site
      decays exponentially for >6h, this prediction was confirmed
      immunohistochemically. Only approximately 5% of the venom is eliminated in 10h;
      approximately 80% of the venom is in the tissues after 2h and remains there for
      >10h.

PMID- 15500850
TI  - Paralytic shellfish poisoning toxins in green mussels (Perna viridis) from the
      Gulf of Paria, Trinidad.
AB  - Paralytic shellfish poisoning (PSP) toxins were determined in green mussels
      (Perna viridis) collected from one collection site in the Gulf of Paria in
      Trinidad in 1999 and 2000. Aqueous extracts of PSP were purified by passage
      through C-18 SPE cartridges, oxidized with peroxide and periodate, respectively,
      then analyzed by HPLC with fluorescence detection. This procedure provided rapid
      and highly sensitive screening of samples for PSP toxins. Further purification of
      PSP-containing extracts using COOH SPE cartridges resulted in the separation and
      identification of individual PSP toxins. The method of analysis was validated by
      spike and recovery experiments, with 85-103% recoveries of mixed toxins. PSP
      toxins determined in our samples in both years were GTX2,3, dcGTX2,3, STX, and
      dcSTX, while GTX1,4 and NeoSTX were only identified in 1999 and 2000,
      respectively. In 1999, GTX1,4, GTX2,3 and dcGTX2,3 predominated, as compared to
      NeoSTX, GTX2,3 and dcGTX2,3 in 2000. However, mussel samples in 2000 contained
      higher total concentrations of detected PSP toxins than those of 1999. These
      results represent the first identification of specific PSP toxins in local
      shellfish and provide a basis for effective monitoring and control of these
      toxins in Trinidad.

PMID- 15500851
TI  - Membrane independent activation of fibroblast proMMP-2 by snake venom: novel
      roles for venom proteinases.
AB  - ProMMP-2 activation by Bothrops asper venom was investigated in mouse
      gastrocnemius muscle, mammalian cell culture and a cell-free system. Zymography
      revealed an increment of latent and activated forms of MMP-2 in muscle
      homogenates 1-3 days after venom injection. To clarify if venom can induce
      expression and activation of MMP-2, independently of the inflammatory response,
      venom was added to cultured human fibroblasts, endothelial and skeletal muscle
      cells, which expressed proMMP-2 constitutively. Venom activated proMMP-2 without
      promoting its expression. Venom also activated and degraded proMMP-2 in
      supernatants collected from fibroblast cultures, indicating that cells are not
      required for this activation. Pretreatment with EDTA increased MMP-2 activation
      and reduced degradation. Venom serine proteinases activated proMMP-2, whereas
      BaP1, a P-I metalloproteinase, predominantly degraded the latent and active forms
      of MMP-2. Moreover, pretreatment of conditioned medium with serine proteinase
      inhibitors greatly reduced the venom-induced activation, suggesting that venom
      proteinases activate MMP-2 via a serine proteinase secreted by fibroblasts. Venom
      also directly activated and degraded purified proMMP-2, albeit requiring a high
      concentration. Thus, B. asper venom proteinases activate and degrade proMMP-2
      without inducing its synthesis. Serine proteinases play a dominant role in the
      activation, whereas metalloproteinases predominantly degrade MMP-2. Activation of
      proMMP-2 by snake venom proteinases, independently of the MT1-MMP/TIMP-2 pathway,
      extracellular matrix degradation or apoptosis, represents a novel mechanism in
      human fibroblasts.

PMID- 15500852
TI  - First report of saxitoxin in octopi.
AB  - We report for the first time, the presence of saxitoxin (STX) in a common
      cephalopod, Octopus (Abdopus) sp. 5, collected from Cooke Point on the northern
      coastline of Western Australia. Sodium channel and saxiphilin based radio
      receptor assays detected saxitoxin-like binding in octopi extracts. Further
      analysis by liquid chromatography-fluorescence detection (LC-FLD) identified STX
      as the major contributing toxin in these samples. The presence of STX was
      confirmed by LC-mass spectrometry and comparison of fragmentation patterns with
      an authentic STX standard. LC-FLD quantitation and conversion of the Octopus sp.
      5 extracts revealed toxin concentrations as high as 246 microg STX/100g tissue,
      more than three times the US, European and Australian regulatory limit for human
      consumption of shellfish of 80 microg STX/100g tissue. There was no evidence of
      tetrodotoxin or other paralytic shellfish toxin derivatives. This level and
      distribution of STX in octopi poses a potential public health risk, particularly
      when routine toxin screening of wild catch is not regulated.

PMID- 15500853
TI  - Accumulation of paralytic shellfish toxins (PST) from the cyanobacterium
      Aphanizomenon issatschenkoi by the cladoceran Daphnia magna.
AB  - In order to access the effects of Paralytic Shellfish Toxins (PST) in freshwater
      environment, the accumulation of PST produced by the cyanobacteria Aphanizomenon
      issatschenkoi in juvenile Daphnia magna was investigated. D. magna was exposed to
      A. issatschenkoi cells (1.2 x 10(6) cells ml(-1)) for 6, 8, 12, 24 and 30 h and
      also to lyophilised material (1 mg ml(-1)) for 24h. Survival and somatic growth
      of the juvenile D. magna was investigated, as was the activity of the
      biotransformation enzyme system glutathione-S-transferases (GSTs). Between 643+/
      65.35 and 1170+/-51.72 pmol PST ml(-1) were detected by HPLC-FLD in D. magna
      culture medium containing cells and 2745+/-64.61 pmol PST toxin ml(-1), in the
      medium containing lyophilised material. PST were detected in D. magna tissues in
      cells exposure (between 6.51 x 10(-2)+/-1.37 x 10(-2) and 3.78 x 10(-1)+/-1.15 x
      10(-2)pmol PST animal(-1)). In D. magna exposed to lyophilised material the mean
      (+/-SD) PST concentration was found to be 6.96 x 10(-3) (+/-3.84 x 10(-3)) pmol
      PST animal(-1). Following exposure to 1.2 x 10(6) cells ml(-1)A. issatschenkoi
      fresh cells growth and survival of D. magna were reduced. D. magna exposed to the
      two A. issatschenkoi treatments (fresh cells and lyophilised material), showed a
      reduction in activity of the cytosolic glutathione-S-transferases (cGSTs). The
      results of this study indicate that D. magna can accumulate PST toxins and that
      the cyanobacterium A. issatschenkoi affects both the fitness and growth potential
      of juvenile D. magna.

PMID- 15500854
TI  - Mojave toxin in venom of Crotalus helleri (Southern Pacific Rattlesnake):
      molecular and geographic characterization.
AB  - Mojave toxin (MT) was detected in five of 25 Crotalus helleri (Southern Pacific
      rattlesnake) sampled using anti-MT antibodies and nucleotide sequence analysis.
      All of the venoms that were positive for MT were collected from Mt San Jacinto in
      Riverside Co., California. Since this population is geographically isolated from
      C. scutulatus scutulatus (Mojave rattlesnake), it is unlikely that this finding
      is due to recent hybridization. MT concentration differences between C. helleri
      and C. s. scutulatus reflected the presence of 'isoforms' of the toxin in the
      venom. Whereas C. s. scutulatus generally has several isoforms of the toxin
      (detected by Western blotting), only one 'isoform' that focused at pI 5.1 was
      detected in C. helleri. Both acidic and basic subunits of MT sequences were
      obtained from C. helleri DNA with primers specific for MT, but only from snakes
      that had MT in their venom. The sequence identity of the C. helleri acidic
      subunit to the C. s. scutulatus subunit was 84.9%, whereas the sequence identity
      of the C. helleri basic subunit was 97% to the C. s. scutulatus basic subunit.
      Using casein, fibrin, and hide powder azure as substrates, assays for proteolytic
      activity suggested that C. helleri possesses several different types of
      metalloproteinases in their venom. However, proteolytic activity was not
      detected, or present in reduced amounts, in specimens having MT. Clinical
      neurotoxicity following envenomation by certain populations of C. helleri may be
      due to MT.

PMID- 15500855
TI  - Intravascular hemolysis induced by Lonomia obliqua caterpillar bristle extract:
      an experimental model of envenomation in rats.
AB  - Hemostatic disturbances are frequent findings in human accidents caused by
      Lonomia obliqua caterpillars in the southern region of Brazil. In severe
      envenomation, patients may present life-threatening bleedings. Such disturbances
      may be mimicked in rats, which also develop intravascular hemolysis. The scope of
      this study was to investigate the time-course and intensity of intravascular
      hemolysis induced by i.d. injection of 750 microg/kg crude L. obliqua bristle
      extract in rats. Total blood cell count, reticulocyte count, plasma hemoglobin
      and haptoglobin assays were performed in control and envenomed rats at 1, 6, 24
      and 48 h after envenomation. Rats presented a drastic drop of haptoglobin levels
      at 1 and 6h with increased plasma hemoglobin levels, a decrease in packed cell
      volume values at 6, 24 and 48 h, and increased reticulocyte counts throughout
      after envenomation. Such observations indicated that intravascular hemolysis
      occurred as early as 1h following envenomation, and lasted for more than 6h.
      Intravascular hemolysis is probably induced by phospholipase A(2) and other
      proteins with direct hemolytic activity present in crude caterpillar bristle
      extract.

PMID- 15500857
TI  - Structure and function of the epidermal growth factor (EGF/ErbB) family of
      receptors.

PMID- 15500858
TI  - The three-dimensional structure of integrins and their ligands, and
      conformational regulation of cell adhesion.
AB  - Integrins are a structurally elaborate family of adhesion molecules that transmit
      signals bidirectionally across the plasma membrane by undergoing large-scale
      structural rearrangements. By regulating cell-cell and cell-matrix contacts,
      integrins participate in a wide-range of biological interactions including
      development, tissue repair, angiogenesis, inflammation and hemostasis. From a
      therapeutic standpoint, integrins are probably the most important class of cell
      adhesion receptors. Structural investigations on integrin-ligand interactions
      reveal remarkable features in molecular detail. These details include the atomic
      basis for divalent cation-dependent ligand binding and how conformational signals
      are propagated long distances from one domain to another between the cytoplasm
      and the extracellular ligand binding site that regulate affinity for ligand, and
      conversely, cytosolic signaling pathways.

PMID- 15500859
TI  - Structures of axon guidance molecules and their neuronal receptors.

PMID- 15500860
TI  - Shared cytokine signaling receptors: structural insights from the gp130 system.
AB  - The vast majority of cytokine signaling is mediated by "shared" receptors that
      form central signaling components of higher-order complexes incorporating ligand
      specific receptors. These include the common gamma chain (gamma(c)), common beta
      chain (beta(c)), and gp130, as well as others. These receptors have the dual
      tasks of cross-reactive cytokine recognition, and formation of precisely oriented
      multimeric signaling assemblies. Currently, detailed structural information on a
      shared receptor complex exists only for gp130, which is a highly pleiotropic
      shared cytokine signaling receptor essential for mammalian cell growth and
      homeostasis. To date, more than 10 different four-helix bundle ligands have been
      identified that incorporate gp130, or one of its close relatives such as LIF
      receptor, into functional oligomeric signaling complexes. In this review we
      summarize our current knowledge of shared receptor recognition and activation,
      with a focus on gp130. We discuss recent structural and functional information to
      analyze overall architectural assemblies of gp130 cytokine complexes and probe
      the basis for the extreme cross-reactivity of gp130 for its multiple cytokine
      ligands.

PMID- 15500861
TI  - The structural basis for biological signaling, regulation, and specificity in the
      growth hormone-prolactin system of hormones and receptors.
AB  - The pituitary hormones growth hormone (GH), prolactin (PRL) and placental
      lactogen (PL), are members of an extensive cytokine superfamily of hormones and
      receptors that share many of the same general structure-function relationships in
      expressing their biological activities. The biology of the pituitary hormones
      involves a very sophisticated interplay of cross-reactivity and specificity.
      Biological activity is triggered via a hormone-induced receptor homodimerization
      process that is regulated by tertiary features of the hormone. These hormones
      have an asymmetric four alpha-helical bundle structure that gives rise to two
      receptor binding sites that have distinctly different topographies and
      electrostatic character. This feature plays an important role in the regulation
      of these systems by producing binding surfaces with dramatically different
      binding affinities to the receptor extracellular domains (ECD). As a consequence,
      the signaling complexes for systems that activate through receptor
      homodimerization are formed in a controlled sequential step-wise manner.
      Extensive biochemical and biophysical characterization of the two hormone
      receptor interfaces indicate that the energetic properties of the two binding
      sites are fundamentally different and that the receptor shows extraordinary
      conformational plasticity to mate with the topographically dissimilar sites on
      the hormone. An unexpected finding has been that the two hormone binding sites
      are allosterically coupled; a certain set of mutations in the higher affinity
      site can produce both conformational and energetic effects in the lower affinity
      site. These effects are so large that at some level they must have played some
      role in the evolution of the molecule.

PMID- 15500862
TI  - Structural analysis of IL-10 and Type I interferon family members and their
      complexes with receptor.

PMID- 15500863
TI  - Assembly of post-receptor signaling complexes for the tumor necrosis factor
      receptor superfamily.
AB  - The tumor necrosis factor (TNF) receptor (TNFR) superfamily comprises more than
      20 type-I transmembrane proteins that are structurally related in their
      extracellular domains and specifically activated by the corresponding superfamily
      of TNF-like ligands. Members of this receptor superfamily are widely distributed
      and play important roles in many crucial biological processes such as lymphoid
      and neuronal development, innate and adaptive immunity, and maintenance of
      cellular homeostasis. A remarkable dichotomy of the TNFR superfamily is the
      ability of these receptors to induce the opposing effects of gene transcription
      for cell survival, proliferation, and differentiation and of apoptotic cell
      death. The intracellular signaling proteins known as TNF receptor associated
      factors (TRAFs) are the major signal transducers for the cell survival effects,
      while the death-domain-containing proteins mediate cell death induction. This
      review summarizes recent structural, biochemical, and functional studies of these
      signal transducers and proposes the molecular mechanisms of the intracellular
      signal transduction.

PMID- 15500864
TI  - NKG2D and Related Immunoreceptors.
AB  - NK cells are crucial components of the innate immune system, capable of directly
      eliminating infected or tumorigenic cells and regulating down-stream adaptive
      immune responses. Unlike T cells, where the key recognition event driving
      activation is mediated by the unique T cell receptor (TCR) expressed on a given
      cell, NK cells express multiple activating and inhibitory cell-surface receptors
      (NKRs), often with overlapping ligand specificities. NKRs display two ectodomain
      structural homologies, either immunoglobulin- or C-type lectin-like (CTLD). The
      CTLD immunoreceptor NKG2D is found on NK cells but is also widely expressed on T
      cells and other immune system cells, providing stimulatory or co-stimulatory
      signals. NKG2D drives target cell killing following engagement of diverse,
      conditionally expressed MHC class I-like protein ligands whose expression can
      signal cellular distress due to infection or transformation. The symmetric,
      homodimeric receptor interacts with its asymmetric, monomeric ligands in similar
      2:1 complexes, with an equivalent surface on each NKG2D monomer binding
      extensively and intimately to distinct, structurally divergent surfaces on the
      ligands. Thus, NKG2D ligand-binding site recognition is highly degenerate,
      further demonstrated by NKG2D's ability to simultaneously accommodate multiple
      non-conservative allelic or isoform substitutions in the ligands. In TCRs,
      "induced-fit" recognition explains cross-reactivity, but structural,
      computational, thermodynamic and kinetic analyses of multiple NKG2D-ligand pairs
      show that rather than classical "induced-fit" binding, NKG2D degeneracy is
      achieved using distinct interaction mechanisms at each rigid interface:
      recognition degeneracy by "rigid adaptation." While likely forming similar
      complexes with their ligand (HLA-E), other NKG2x NKR family members do not
      require such recognition degeneracy.

PMID- 15500865
TI  - Ionotropic glutamate receptor recognition and activation.
AB  - Ionotropic glutamate receptors are the major excitatory neurotransmitters in
      mammalian brain but are found throughout the animal kingdom as well as in plants
      and bacteria. A great deal of progress in understanding the structure of these
      essential neurotransmitter receptors has been made since the first examples were
      cloned and sequenced in 1989. The atomic structure of the ligand-binding domain
      of several ionotropic glutamate receptors has been determined, and a great deal
      of progress has been made in relating the structural properties of the binding
      site to the function of the intact receptor. In addition, the identification of
      glutamate receptors from a wide variety of organisms ranging from several types
      of bacteria to Arabidopsis to a range of animal species has made glutamate
      receptors a molecular laboratory for studying the evolution of proteins. The fact
      that glutamate receptors are a particularly ancient intercellular signaling
      molecule suggests a potential role in the transition from single celled to
      multicellular organisms. This review focuses on the structure and dynamics of
      ionotropic glutamate receptors and their relation to the function and evolution
      of these proteins.

PMID- 15500866
TI  - Chemokine-receptor interactions: GPCRs, glycosaminoglycans and viral chemokine
      binding proteins.
AB  - A key feature of the immune system is the migration of leukocytes throughout the
      organism in an effort to patrol for infectious pathogens, tissue damage, and
      other physiological insults. This remarkable surveillance system is controlled by
      a family of proteins called chemokines (chemoattractant cytokines), and their
      respective receptors. Originally discovered because of their role in cell
      recruitment during inflammation, it is now well recognized that chemokines are
      also involved in other diverse processes including lymphocyte development and
      homing, organogenesis, and neuronal communication. While chemokines have evolved
      largely for host protection, their ability to induce cell damage and
      inappropriate cell recruitment, can lead to disease. Thus, there is considerable
      interest in developing antagonists. In this review we emphasize what is known
      about the structural biology of chemokines, chemokine receptors, and interactions
      with cell surface glycosaminoglycans. We also briefly describe their role in
      certain diseases and strategies for interfering with chemokine function that have
      emerged from mechanistic and structural understanding of their function. Finally
      we discuss viral mechanisms for sabotaging or manipulating the chemokine system,
      in part to illustrate the level of molecular mimicry that viruses have achieved
      and the evolutionary pressure imposed on the immune system by these pathogens.

PMID- 15500867
TI  - Chemotaxis receptors and signaling.
AB  - Chemotaxis is an important cellular response common in biology. In many
      chemotaxing cells the signal that regulates movement is initiated by G protein
      coupled receptors on the cell surface that bind specific chemoattractants. These
      receptors share important structural similarities with other G protein-coupled
      receptors, including rhodopsin, which currently serves as the best starting point
      for modeling their structures. However, the chemotaxis receptors also share a
      number of relatively unique structural features that are less common in other
      GPCRs. The chemoattractant ligands of chemotaxis receptors exhibit a broad
      variety of sizes and chemical properties, ranging from small molecules and
      peptides to protein ligands. As a result, different chemotaxis receptors have
      evolved specialized mechanisms for the early steps of ligand binding and receptor
      activation. The mechanism of transmembrane signaling is currently under intensive
      study and several alternate mechanisms proposing different conformational
      rearrangements of the transmembrane helices have been proposed. Some chemotaxis
      receptors are proposed to form dimers, and in certain cases dimer formation is
      proposed to play a role in transmembrane signaling. In principle the structural
      and dynamical changes that occur during transmembrane signaling could be
      specialized for different receptors, or could be broadly conserved. Extensive
      mutagenesis studies have been carried out, and have begun to identify critical
      residues involved in ligand binding, receptor activation, and transmembrane
      signaling.

PMID- 15500868
TI  - Crime and (age-appropriate) punishment.

PMID- 15500869
TI  - Aiding decision making for baby Charlotte and baby Luke.

PMID- 15500870
TI  - Brain atrophy, interferon beta, and treatment trials in multiple sclerosis.

PMID- 15500871
TI  - Are beta2-adrenoceptor polymorphisms important in asthma--an unravelling story.

PMID- 15500873
TI  - Self-management in chronic illness.

PMID- 15500872
TI  - Drug-eluting stents: some bare facts.

PMID- 15500874
TI  - Success of clinical trials in childhood Wilms' tumour around the world.

PMID- 15500876
TI  - Not-for-profit drugs--no longer an oxymoron?

PMID- 15500875
TI  - Biology of infectious proteins: lessons from yeast prions.

PMID- 15500880
TI  - Historical keywords: health.

PMID- 15500881
TI  - Harms and benefits of screening to prevent cervical cancer.

PMID- 15500882
TI  - Harms and benefits of screening to prevent cervical cancer.

PMID- 15500883
TI  - Harms and benefits of screening to prevent cervical cancer.

PMID- 15500885
TI  - Harms and benefits of screening to prevent cervical cancer.

PMID- 15500886
TI  - COX-2 inhibitors and risk of heart failure.

PMID- 15500887
TI  - Animal testing: call for open, scientific debate.

PMID- 15500888
TI  - The best route.

PMID- 15500889
TI  - COX-2 inhibitors and risk of heart failure.

PMID- 15500891
TI  - Obesity epidemic.

PMID- 15500892
TI  - Depression and anxiety in developing countries.

PMID- 15500893
TI  - Interferon beta-1a for brain tissue loss in patients at presentation with
      syndromes suggestive of multiple sclerosis: a randomised, double-blind, placebo
      controlled trial.
AB  - BACKGROUND: In patients who present with clinically isolated syndromes suggestive
      of multiple sclerosis, interferon beta-1a is effective in delaying evolution to
      clinically definite disease and in reducing MRI-measured disease activity. We
      aimed to assess whether this drug can also reduce the rate of brain volume
      decrease in such patients enrolled in the ETOMS (early treatment of multiple
      sclerosis) trial. METHODS: MRI data for brain volume measurements at baseline,
      month 12, and month 24 were available from 131, 111, and 112 patients assigned
      treatment (22 microg interferon beta-1a), and 132, 98, and 99 patients assigned
      placebo respectively. Normalised brain parenchymal volume (NBV) at baseline and
      percentage brain volume changes (PBVC) were measured with a fully-automated
      segmentation technique. The primary endpoint was conversion to clinically
      definite multiple sclerosis due to clinical relapse. Analysis was by intention to
      treat. FINDINGS: 41 (31%) of 131 patients on interferon beta-1a and 62 (47%) of
      132 on placebo converted to clinically definite multiple sclerosis (odds ratio
      0.52 [95% CI 0.31-0.86], p=0.0115). Mean PBVC for patients on placebo was -0.83%
      during the first year, -0.67% during the second year, and -1.68% during the
      entire study period. Respective values for treated patients were -0.62%, -0.61%,
      and -1.18%. The changes in brain volume were significant in both groups at all
      timepoints. A significant treatment effect was detected for month 24 versus
      baseline values (p=0.0031). The number of new T2 lesions formed during the first
      year correlated weakly with PBVC during the second year. INTERPRETATION: Early
      treatment with interferon beta-1a is effective in reducing conversion to
      clinically definite multiple sclerosis and in slowing progressive loss of brain
      tissue in patients with clinically isolated syndromes. The modest correlation
      between new lesion formation and brain volume decrease suggests that inflammatory
      and neurodegenerative processes are, at least partly, dissociated from the
      earliest clinical stage of multiple sclerosis onwards.

PMID- 15500894
TI  - Single-dose brachytherapy versus metal stent placement for the palliation of
      dysphagia from oesophageal cancer: multicentre randomised trial.
AB  - BACKGROUND: Both single-dose brachytherapy and self-expanding metal stent
      placement are commonly used for palliation of oesophageal obstruction due to
      inoperable cancer, but their relative merits are unknown. We undertook a
      randomised trial to compare the outcomes of brachytherapy and stent placement in
      patients with oesophageal cancer. METHODS: Nine hospitals in the Netherlands
      participated in our study. Between December, 1999, and June, 2002, 209 patients
      with dysphagia from inoperable carcinoma of the oesophagus or oesophagogastric
      junction were randomly assigned to stent placement (n=108) or single-dose (12 Gy)
      brachytherapy (n=101), and were followed up after treatment. Primary outcome was
      relief of dysphagia during follow-up, and secondary outcomes were complications,
      treatment for persistent or recurrent dysphagia, health-related quality of life,
      and costs. Analysis was by intention to treat. FINDINGS: Nine patients (six
      [brachytherapy] vs three [stent placement]) did not receive their allocated
      treatments. None was lost to follow-up. Dysphagia improved more rapidly after
      stent placement than after brachytherapy, but long-term relief of dysphagia was
      better after brachytherapy. Stent placement had more complications than
      brachytherapy (36 [33%] of 108 vs 21 [21%] of 101; p=0.02), which was mainly due
      to an increased incidence of late haemorrhage (14 [13%] of 108 vs five [5%] of
      101; p=0.05). Groups did not differ for persistent or recurrent dysphagia
      (p=0.81), or for median survival (p=0.23). Quality-of-life scores were in favour
      of brachytherapy compared with stent placement. Total medical costs were also
      much the same for stent placement (8215) and brachytherapy (8135).
      INTERPRETATION: Despite slow improvement, single-dose brachytherapy gave better
      long-term relief of dysphagia than metal stent placement. Since brachytherapy was
      also associated with fewer complications than stent placement, we recommend it as
      the primary treatment for palliation of dysphagia from oesophageal cancer.

PMID- 15500895
TI  - Use of regularly scheduled albuterol treatment in asthma: genotype-stratified,
      randomised, placebo-controlled cross-over trial.
AB  - BACKGROUND: The issue of whether regular use of an inhaled beta2-adrenergic
      agonist worsens airflow and clinical outcomes in asthma is controversial.
      Retrospective studies have suggested that adverse effects occur in patients with
      a genetic polymorphism that results in homozygosity for arginine (Arg/Arg),
      rather than glycine (Gly/Gly), at aminoacid residue 16 of the beta2-adrenergic
      receptor. However, the existence of any genotype-dependent difference has not
      been tested in a prospective clinical trial. METHODS: Patients with mild asthma,
      not using a controller medication, were enrolled in pairs matched for forced
      expiratory volume in 1 s (FEV1) according to whether they had the Arg/Arg (n=37;
      four of 41 matches withdrew before randomisation) or Gly/Gly (n=41) genotype.
      Regularly scheduled treatment with albuterol or placebo was given in a masked,
      cross-over design, for 16-week periods. During the study, as-needed albuterol use
      was discontinued and ipratropium bromide was used as needed. Morning peak
      expiratory flow rate (PEFR) was the primary outcome variable. The primary
      comparisons were between treatment period for each genotype; the secondary
      outcome was a treatment by genotype effect. Analyses were by intention to treat.
      FINDINGS: During the run-in period, when albuterol use was kept to a minimum,
      patients with the Arg/Arg genotype had an increase in morning PEFR of 23 L/min
      (p=0.0162); the change in patients with the Gly/Gly genotype was not significant
      (2 L/min; p=0.8399). During randomised treatment, patients with the Gly/Gly
      genotype had an increase in morning PEFR during treatment with regularly
      scheduled albuterol compared with placebo (14 L/min [95% CI 3 to 25]; p=0.0175).
      By contrast, patients with the Arg/Arg genotype had lower morning PEFR during
      treatment with albuterol than during the placebo period, when albuterol use was
      limited (-10 L/min [-19 to -2]; p=0.0209). The genotype-attributable treatment
      difference was therefore -24 L/min (-37 to -12; p=0.0003). There were similar
      genotype-specific effects in FEV1, symptoms, and use of supplementary reliever
      medication. INTERPRETATION: Genotype at the 16th aminoacid residue of the beta2
      adrenergic receptor affects the long-term response to albuterol use.
      Bronchodilator treatments avoiding albuterol may be appropriate for patients with
      the Arg/Arg genotype.

PMID- 15500897
TI  - Late thrombosis in drug-eluting coronary stents after discontinuation of
      antiplatelet therapy.
AB  - Although the safety profiles of coronary stents eluting sirolimus or paclitaxel
      do not seem to differ from those of bare metal stents in the short-to-medium
      term, concern has arisen about the potential for late stent thromboses related to
      delayed endothelialisation of the stent struts. We report four cases of
      angiographically-confirmed stent thrombosis that occurred late after elective
      implantation of polymer-based paxlitaxel-eluting (343 and 442 days) or sirolimus
      eluting (335 and 375 days) stents, and resulted in myocardial infarction. All
      cases arose soon after antiplatelet therapy was interrupted. If confirmed in
      systematic long-term follow-up studies, our findings have potentially serious
      clinical implications.

PMID- 15500896
TI  - Oestrogen treatment to reduce the adult height of tall girls: long-term effects
      on fertility.
AB  - BACKGROUND: Treatment with oestrogen to reduce the adult height of tall girls has
      been available since the 1950s. We undertook a retrospective cohort study to
      assess the long-term effects of this treatment on fertility. METHODS: Eligible
      participants were identified from the records of Australian paediatric
      endocrinologists who assessed tall girls from 1959 to 1993, and from self
      referrals. Individuals included girls who had received oestrogen treatment
      (diethylstilboestrol or ethinyl oestradiol) (treated group) and those who were
      assessed but not treated (untreated group). Information about reproductive
      history was sought by telephone interview. FINDINGS: 1432 eligible individuals
      were identified, of whom 1243 (87%) could be traced. Of these, 780 (63%)
      completed interviews: 651 were identified from endocrinologists' records, 129
      were self-referred. Treated (n=371) and untreated (n=409) women were similar in
      socioeconomic and other characteristics. After adjustment for age, treated women
      were more likely to have ever tried for 12 months or more to become pregnant
      without success (relative risk [RR] 1.80, 95% CI 1.40-2.30); more likely to have
      seen a doctor because they were having difficulty becoming pregnant (RR 1.80,
      1.39-2.32); and more likely to have ever taken fertility drugs (RR 2.05, 1.39
      3.04). Time to first pregnancy analysis showed that the treated group was 40%
      less likely to conceive in any given menstrual cycle of unprotected intercourse
      (age-adjusted fecundability ratio 0.59, 95% CI 0.46-0.76). These associations
      persisted when self-referred women were excluded. INTERPRETATION: High-dose
      oestrogen treatment in adolescence seems to reduce female fertility in later
      life. This finding has implications for current treatment practices and for our
      understanding of reproductive biology.

PMID- 15500898
TI  - Omphalitis.

PMID- 15500899
TI  - Self-management interventions for chronic illness.
AB  - An increasing number of interventions have been developed for patients to better
      manage their chronic illnesses. They are characterised by substantial
      responsibility taken by patients, and are commonly referred to as self-management
      interventions. We examine the background, content, and efficacy of such
      interventions for type 2 diabetes, arthritis, and asthma. Although the content
      and intensity of the programmes were affected by the objectives of management of
      the illness, the interventions differed substantially even within the three
      illnesses. When comparing across conditions, it is important to recognise the
      different objectives of the interventions and the complexity of the issues that
      they are attempting to tackle. For both diabetes and asthma, the objectives are
      concerned with the underlying control of the condition with clear strategies to
      achieve the desired outcome. By contrast, strategies to deal with symptoms of
      pain and the consequences of disability in arthritis can be more complex. The
      interventions that were efficacious provide some guidance as to the components
      needed in future programmes to achieve the best results. But to ensure that these
      results endure over time remains an important issue for self-management
      interventions.

PMID- 15500900
TI  - Virtual reality training for the operating room and cardiac catheterisation
      laboratory.
AB  - CONTEXT: High-profile cases of medical errors in the USA and UK, and major
      reports from organisations such as the US Institute of Medicine and UK Senate of
      Surgery, have sensitised the public and medical profession. Training is a key
      area that must be tackled to positively affect the problem of medical errors,
      especially in surgery and interventional cardiology. Despite the radically novel
      skills required for minimally invasive surgery or interventional cardiology,
      current training has gone largely unchanged. At the end of the 20th century, the
      public and the medical profession have concluded that training on patients is no
      longer acceptable. STARTING POINT: Recently, Teodor Grantcharov and colleagues
      (Br J Surg 2004; 91: 146-50) did a randomised double-blind trial which showed
      that training by virtual reality (VR) significantly reduces objectively assessed
      intraoperative errors in laparoscopic cholecystectomy. They used a low-fidelity
      VR simulator. Much more sophisticated VR simulators exist for endoscopy,
      gynaecology, laparoscopy, orthopaedics, otolaryngology, robotics, and urology.
      There are few studies on the efficacy of these simulators in improving the safety
      of procedures on patients. WHERE NEXT: There needs to be more large and
      multicentre studies. Technical skills training for procedural based medicine
      continues to be an ad-hoc mentor-based experience for the trainee, with
      experience gained by practising on patients. The skills required now are so
      difficult to learn that this type of training is no longer acceptable. VR
      simulator-based training does work, but further empirical evidence is required to
      convince the more conservative members of the medical community.

PMID- 15500901
TI  - Achieving universal coverage with health interventions.
AB  - Cost-effective public health interventions are not reaching developing country
      populations who need them. Programmes to deliver these interventions are too
      often patchy, low quality, inequitable, and short-lived. We review the challenges
      of going to scale, building on known, effective interventions to achieve
      universal coverage. One challenge is to choose interventions consistent with the
      epidemiological profile of the population. A second is to plan for context
      specific delivery mechanisms effective in going to scale, and to avoid uniform
      approaches. A third is to develop innovative delivery mechanisms that move
      incrementally along the vertical-to-horizontal axis as health systems gain
      capacity in service delivery. The availability of sufficient funds is essential,
      but constraints to reaching universal coverage go well beyond financial issues.
      Accurate estimates of resource requirements need a full understanding of the
      factors that limit intervention delivery. Sound decisions need to be made about
      the choice of delivery mechanisms, the sequence of action, and the pace at which
      services can be expanded. Strong health systems are required, and the time frames
      and funding cycles of national and international agencies are often
      unrealistically short.

PMID- 15500902
TI  - Kaposi's sarcoma.

PMID- 15500903
TI  - A useless error?

PMID- 15500904
TI  - Dysuria and a headache.

PMID- 15500905
TI  - Role of apoptosis in remodeling after myocardial infarction.
AB  - The magnitude of an acute myocardial infarction (MI; i.e., number of dead
      cardiomyocytes) is the most critical determinant of subsequent left ventricular
      remodeling and heart failure. Also affecting the post-infarction disease process,
      however, are events occurring during the subacute and chronic stages of the
      infarction, including late cardiomyocyte death, cardiomyocyte hypertrophy,
      fibrosis, and expression of various cytokines. Additionally, it has been
      suggested that apoptosis may be responsible for a significant amount of
      cardiomyocyte death during the acute ischemic stage, as well as for a progressive
      loss of surviving cells during the subacute and chronic stages. However, there is
      very little direct morphological evidence of apoptosis occurring at any stage of
      MI, despite the availability of much indirect evidence that includes detection of
      DNA fragmentation and apoptosis-related factors. For that reason, the potential
      efficacy of therapeutic intervention to prevent apoptosis remains controversial.
      This review will survey available data from both animals and humans to critically
      assess the role of cardiomyocyte apoptosis during MI and its relevance to
      myocardial remodeling and heart failure. Also considered will be nonmyocyte
      interstitial cells, which have received less attention than myocytes despite
      definitive evidence of their apoptosis in the infarcted heart and recent studies
      suggesting that blockade of apoptosis among these cells mitigates post-infarction
      cardiac remodeling and heart failure. We conclude from our survey that there are
      many hurdles to surmount before regulation of apoptosis can be clinically applied
      in the treatment of MI and other heart diseases.

PMID- 15500906
TI  - Neurotransmitter transporter trafficking: endocytosis, recycling, and regulation.
AB  - Sodium- and chloride-dependent transporters in the SLC6 gene family are key
      regulators of extracellular neurotransmitter levels and are required for normal
      neurotransmission. Copious evidence supports the premise that membrane
      trafficking dynamically modulates transporter surface expression in response to
      psychostimulant exposure, receptor activation, and neuronal activity. Recent work
      from our group and others demonstrates that many SLC6 transporters not only
      traffic in response to exogenous stimuli, but also constitutively traffic, with
      exogenous signaling modulating intrinsic transporter trafficking kinetics. This
      review focuses on what is currently understood about constitutive and regulated
      transporter trafficking, and poses a model wherein endocytic trafficking
      dynamically primes transporters for multi-faceted regulatory events.

PMID- 15500907
TI  - Delivery of therapeutic agents to the central nervous system: the problems and
      the possibilities.
AB  - The presence of a blood-brain barrier (BBB) and a blood-cerebrospinal fluid
      barrier presents a huge challenge for effective delivery of therapeutics to the
      central nervous system (CNS). Many potential drugs, which are effective at their
      site of action, have failed and have been discarded during their development for
      clinical use due to a failure to deliver them in sufficient quantity to the CNS.
      In consequence, many diseases of the CNS are undertreated. In recent years, it
      has become clear that the blood-CNS barriers are not only anatomical barriers to
      the free movement of solutes between blood and brain but also transport and
      metabolic barriers. The cell association, sometimes called the neurovascular
      unit, constitutes the BBB and is now appreciated to be a complex group of
      interacting cells, which in combination induce the formation of a BBB. The
      various strategies available and under development for enhancing drug delivery to
      the CNS are reviewed.

PMID- 15500908
TI  - The gene transcription factor cyclic AMP-responsive element binding protein: role
      in positive and negative affective states of alcohol addiction.
AB  - The gene transcription factor cyclic adenosine monophosphate (cAMP)-responsive
      element binding (CREB) protein is a nuclear protein that regulates synaptic
      plasticity via modulating the expression of several (cAMP)-inducible genes.
      Alcohol addiction is a complex psychiatric disorder and is characterized by a
      compulsive and uncontrolled pattern of alcohol drinking by an individual in spite
      of the adverse consequences of its abuse. Ethanol produces both euphoric (reward
      and reinforcing) and dysphoric (negative withdrawal reactions) effects and these
      are most likely involved in the initiation and maintenance of alcohol use and
      abuse. Several neurotransmitter systems in the brain might be involved in the
      effects of alcohol but the exact molecular mechanisms of both the positive and
      negative affective states of alcohol abuse are still unclear. Recent research in
      molecular neurosciences using animal models have identified the role of extended
      amygdaloid (shell structures of nucleus accumbens [NAc] and central and medial
      amygdaloid nuclei) CREB signaling in positive and negative affective states of
      alcohol drinking behaviors. This review article highlights the current findings
      on the role of nucleus accumbal and amygdaloid CREB signaling in behavioral
      consequences of alcohol use and abuse.

PMID- 15500909
TI  - Functions of 5-HT2A receptor and its antagonists in the cardiovascular system.
AB  - The serotonin (5-hydroxytryptamine, 5-HT) receptors have conventionally been
      divided into seven subfamilies, most of which have several subtypes. Among them,
      5-HT(2A) receptor is associated with the contraction of vascular smooth muscle,
      platelet aggregation and thrombus formation and coronary artery spasms.
      Accordingly, selective 5-HT(2A) antagonists may have potential in the treatment
      of cardiovascular diseases. Sarpogrelate, a selective 5-HT(2A) antagonist, has
      been introduced clinically as a therapeutic agent for the treatment of ischemic
      diseases associated with thrombosis. Molecular modeling studies also suggest that
      sarpogrelate is a 5-HT(2A) selective antagonist and is likely to have
      pharmacological effects beneficial in the treatment of cardiovascular diseases.
      This review describes the above findings as well as the signaling linkages of the
      5-HT(2A) receptors and the mode of agonist binding to 5-HT(2A) receptor using
      data derived from molecular modeling and site-directed mutagenesis.

PMID- 15500910
TI  - Unique kinetic mechanism of Plasmodium falciparum adenylosuccinate synthetase.
AB  - Adenylosuccinate synthetase (AdSS) catalyses the Mg(2+) dependent formation of
      adenylosuccinate from IMP and aspartate, the reaction being driven by the
      hydrolysis of GTP to GDP. All characterized AdSS thus far exhibit a random
      kinetic mechanism. We present here kinetic evidence that unlike all other AdSS,
      Plasmodium falciparum AdSS (PfAdSS) has ordered substrate binding. Inhibition
      studies show that binding of GTP requires IMP binding while aspartate binds to
      the enzyme-IMP-GTP complex. A structural basis for this difference in mechanism
      is presented. Kinetically, PfAdSS is closer to the mouse acidic isozyme rather
      than to the mouse basic isozyme. The mouse acidic isozyme is thought to play a
      role in the purine nucleotide biosynthetic pathway. Regulation of PfAdSS in vivo
      can therefore, be expected to be similar to the mouse acidic isozyme, in
      agreement with the role of PfAdSS as the only pathway for the synthesis of
      adenine nucleotides in the parasite. However, PfAdSS differs from both the
      mammalian homologs in that fructose-1,6-bisphosphate, a potent inhibitor of the
      mammalian enzyme, is an activator of PfAdSS. The differences highlighted here are
      promising in terms of species-specific drug design, targeting this essential
      enzyme in the parasite.

PMID- 15500911
TI  - Characterization of primate trypanosome lytic factors.
AB  - Humans are one of the few species that resist infection by Trypanosoma brucei
      brucei because the parasites are killed by lytic factors found in human serum.
      Trypanosome lytic factors (TLFs) are protein/lipid complexes that contain
      apolipoprotein A-I (apoA-I), and are therefore a class of high density
      lipoproteins (HDLs). Haptoglobin-related protein (Hpr) is a unique protein
      component of TLFs, and its expression has only been demonstrated in humans.
      Trypanolytic activity has only been found in the sera of five primates: humans,
      gorillas, mandrills, baboons and sooty mangabeys. We describe here previously
      unidentified components of highly purified human TLF1: apolipoprotein L-I (apoL
      I), human cathelicidin antimicrobial peptide 18 (hCAP18) and
      glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD). However, we
      found that hCAP18 and GPI-PLD, along with apoA-I, are common components of both
      lytic and non-lytic primate HDLs. In contrast, Hpr, which has been previously
      implicated as the main lytic component of TLF1, was a unique component of all
      trypanolytic primate HDLs. Furthermore, a polyclonal antiserum to Hpr neutralized
      the lytic activity from humans and baboons. ApoL-I, a candidate lytic component
      of human serum, was not immunologically or genetically detectable in two primate
      species with lytic activity. Polyclonal antiserum to apoL-I also did not
      neutralize TLF activity in a total human HDL preparation. These findings suggest
      that apoL-I is not essential in all primate TLFs, and apoL-I alone is not
      sufficient for optimal trypanosome lytic activity in human TLF.

PMID- 15500912
TI  - Double-stranded RNA mediates homology-dependent gene silencing of gamma-tubulin
      in the human parasite Entamoeba histolytica.
AB  - Approaches that eliminate mRNA are a powerful tool for reverse genetics
      applications in eukaryotic microbes for which gene replacement techniques have
      not yet been developed. Here, for the first time, we demonstrate that RNA
      duplexes efficiently inhibit gene expression when introduced into the human
      parasite Entamoeba histolytica. Chemically synthesized, small interfering RNA
      (siRNA) were highly specific and efficient in silencing parasite gamma-tubulin
      mRNA. Use of specific antibodies revealed that microtubules and gamma-tubulin
      were intra-nuclear in E. histolytica. The RNAi approach to modulation of gamma
      tubulin mRNA resulted in loss of the highly organized microtubule array an
      observation that correlates with a significant reduction of gamma-tubulin as well
      as of the specific mRNA. Our results suggest that gamma-tubulin is essential for
      microtubule nucleation in E. histolytica.

PMID- 15500913
TI  - Malaria parasite-inhibitory antibody epitopes on Plasmodium falciparum merozoite
      surface protein-1(19) mapped by TROSY NMR.
AB  - Plasmodium falciparum merozoite surface protein 1 (MSP1)(19), the C-terminal
      fragment of merozoite surface protein 1, is a leading candidate antigen for
      development of a vaccine against the blood stages of the malaria parasite. Many
      human and animal studies have indicated the importance of MSP1(19)-specific
      immune responses. Anti-MSP1(19) antibodies can prevent invasion of red blood
      cells by P. falciparum parasites in vitro. However, the fine specificity of anti
      MSP1(19) antibodies is also important, as only a fraction of monoclonal
      antibodies (mAbs) have parasite-inhibitory activity in vitro. Human sera from
      malaria-endemic locations show strong MSP1(19) reactivity, but individual serum
      samples vary greatly in inhibitory activity. NMR is an excellent method for
      studying protein-protein interactions, and has been used widely to study binding
      of peptides representing known epitopes (as well as non-protein antigens) to
      antibodies and antibody fragments. The recent development of transverse
      relaxation optimized spectroscopy (TROSY) and related methods has significantly
      extended the maximum size limit of molecules that can be studied by NMR. TROSY
      NMR experiments produce high quality spectra of Fab complexes that allow the
      mapping of epitopes by the chemical shift perturbation technique on a complete,
      folded protein antigen such as MSP1(19). We studied the complexes of P.
      falciparum MSP1(19) with Fab fragments from three monoclonal antibodies. Two of
      these antibodies have parasite-inhibitory activity in vitro, while the third is
      non-inhibitory. NMR epitope mapping showed a close relationship between binding
      sites for the two inhibitory antibodies, distinct from the location of the non
      inhibitory antibody. Together with a previously published crystal structure of
      the P. falciparum MSP1(19) complex with the Fab fragment of another non
      inhibitory antibody, these results revealed a surface on MSP1(19) where
      inhibitory antibodies bind. This information will be useful in evaluating the
      anti-MSP1(19) immune response in natural populations from endemic areas, as well
      as in vaccine trials. It will also be valuable for optimizing the MSP1(19)
      antigen by rational vaccine design. This work also shows that TROSY NMR
      techniques are very effective for mapping conformational epitopes at the level of
      individual residues on small- to medium-sized proteins, provided that the antigen
      can be expressed in a system amenable to stable isotope labelling, such as
      bacteria or yeast.

PMID- 15500915
TI  - Double cross-over gene replacement within the sec 7 domain of a GDP-GTP exchange
      factor from Plasmodium falciparum allows the generation of a transgenic brefeldin
      A-resistant parasite line.
AB  - High molecular weight ADP ribosylation factor GDP-GTP exchange factors (ARF-GEF)
      play an essential role in the formation of COP I coated transport vesicles and
      are characterized by a structurally and functionally conserved sec 7 domain. The
      genome of the malaria parasite Plasmodium falciparum encodes a single ARF-GEF
      that contains an unusual sec 7 domain. In comparison to the sec 7 domain of other
      eukaryotes, the plasmodial sec 7 domain is characterized by an insertion sequence
      of 146 amino acids that disrupt helices essential for the GDP-GTP exchange
      activity of the protein. In a previous study we have shown a correlation between
      a methionine to isoleucine exchange in helix H of the sec 7 domain and resistance
      to brefeldin A in a parasite line generated by drug selection. Here we have
      transfected brefeldin A sensitive parasites with plasmid constructs containing
      the sec 7 domain of the resistant line either with or without the insertion
      sequence. Transfection with sec 7 sequences including the insertion resulted in
      brefeldin A resistant parasites in which double cross-over recombination had
      replaced the endogenous sec 7 sequences with the transgenic sequences. Thus, the
      point mutation in helix H is sufficient to confer brefeldin A resistance in P.
      falciparum. Transfections using constructs lacking the insertion did not result
      in resistant parasites. Gene replacement by targeted double cross-over
      recombination is a rare event in P. falciparum. This approach has taken advantage
      of the fact that the successful integration of the transgene results in a drug
      selectable phenotype. We anticipate that the strategy described here will be
      useful for the identification of mutations within target genes that have the
      potential to confer increased drug resistance.

PMID- 15500914
TI  - A SICAvar switching event in Plasmodium knowlesi is associated with the DNA
      rearrangement of conserved 3' non-coding sequences.
AB  - Plasmodium knowlesi variant antigens are expressed at the surface of infected
      erythrocytes and are encoded by the Schizont Infected Cell Agglutination variant
      antigen (SICAvar) multigene family. The 3' region of the SICAvar gene locus
      encoding the 205 kDa variant antigen expressed in the Pk1(B+)1+ parasites was
      found to be altered compared to the Pk1(A+) parental clone. Here we report that
      this alteration is the result of a DNA rearrangement and that the original and
      altered 205 SICAvar alleles appear to encode bona fide variant antigens.
      Importantly, 205A and 205B SICAvar RNA sequences are detectable in similar
      apparent quantities as determined by quantitative real-time reverse-transcription
      polymerase chain reaction (qRT-PCR) amplification experiments. However,
      expression of the 205 kDa SICA protein at the surface of the infected erythrocyte
      is not characteristic of the Pk1(A+) parasites and the 205 SICAvar transcript has
      not been detected in Pk1(A+) parasites by northern blot analysis. Furthermore, we
      report that many distinct SICAvar transcripts were detected in P. knowlesi
      Pk1(B+)1+ cDNA library hybridization screens. Of special interest, in light of
      these data, distinctive differences at the 3' end of the 205A and 205B alleles
      are observed, which may be of functional importance. An analysis of the 3'
      untranslated region (UTR) of SICAvar genes in more than 100 sequences revealed a
      surprising common sequence pattern characterized by blocks of imperfect, GT-rich,
      heptad repeated motifs (Block I), followed by A and T rich homopolymers (Block
      II) and in a large number of genes, GC-rich segments (Block III). We show that
      this region undergoes extensive recombination and that the preferential stability
      of the 205 SICAvar transcript in Pk1(B+)1+ parasites may be associated with the
      presence of its specific Block III sequences. We speculate that the conserved yet
      polymorphic SICAvar 3'UTR sequences, and comparable regions in P. falciparum var
      genes, function in the stage-specific and developmentally regulated post
      transcriptional gene silencing (PTGS) of variant antigen transcripts.

PMID- 15500916
TI  - The Schistosoma mansoni soluble proteome: a comparison across four life-cycle
      stages.
AB  - Differential analysis of immune responses to schistosomes has routinely been
      performed using complex mixtures of soluble proteins from various life-cycle
      stages, on the assumption that these differed significantly in composition.
      Proteomic techniques now allow us to characterise and compare such mixtures. The
      soluble proteins from cercariae, lung-schistosomula, adult worms and eggs of
      Schistosoma mansoni were separated by high-resolution two-dimensional
      electrophoresis and the resulting images analysed using appropriate software. A
      high degree of quantitative and qualitative similarity in spot pattern was
      revealed across the life-cycle, greatest between adjacent stages. To initiate
      mapping of these soluble proteomes, the 40 most abundant spots in each
      preparation, accounting for 21-46% of the total protein, were subjected to
      peptide fingerprinting by mass spectrometry. On average 55% of the spots were
      identified, but overall, these comprised only 32 different protein species. With
      one exception all proteins originated in the cytosol and 24 of the 32 had
      previously been pinpointed by virtue of their immunoreactivity, including four of
      the WHO priority vaccine candidates. The similarity in composition between the
      four preparations means that they are unlikely to discriminate adequately between
      immune responses to different life-cycle stages and argues strongly for the need
      to identify true stage-specific marker proteins. Equally, it is difficult to
      reconcile the abundance and immunogenicity of such cytosolic proteins with their
      status as vaccine candidates, as it is unlikely they will be accessible to the
      immune system in an intact parasite.

PMID- 15500917
TI  - Both of the Rab5 subfamily small GTPases of Trypanosoma brucei are essential and
      required for endocytosis.
AB  - Endocytosis is an essential process in Trypanosoma brucei and all evidence
      suggests it is exclusively clathrin-mediated. The trypanosome genome encodes two
      Rab5 proteins, small GTPases that play a role in very early stages of
      endocytosis. In the mammalian bloodstream stage TbRAB5A localises to compartments
      containing internalised antibody, variant surface glycoprotein (VSG) and
      transferrin, whilst TbRAB5B localises to compartments containing the
      transmembrane protein ISG(100). Dominant-active forms of TbRAB5A stimulate
      endocytosis in procyclic forms and alter the kinetics of anti-VSG antibody and
      transferrin turnover in bloodstream stages. Similar mutants of TbRAB5B increase
      fluid phase uptake in procyclic cells but do not significantly affect endocytosis
      in bloodstream forms. Here, we use RNA interference to evaluate the relative
      importance of TbRAB5A and TbRAB5B and show that both GTPases are essential in the
      bloodstream form. Depletion of either TbRAB5A or TbRAB5B results in morphological
      abnormalities, including enlargement of the flagellar pocket, consistent with a
      potent block to endocytosis. Also, RNAi compromises transferrin accumulation in
      both cases but induces distinct patterns of mislocalisation of endosomal markers.
      Finally, RNAi of either TbRAB5A or TbRAB5B results in a decrease in levels of
      clathrin. Taken together, these data indicate that both TbRAB5A and TbRAB5B are
      required for endocytosis in trypanosomes and demonstrate that there are multiple
      essential endocytic routes in this organism.

PMID- 15500918
TI  - Cloning and expression of a Na(+), K(+)-ATPase alpha-subunit from Taenia solium
      (TNaK1alpha).
AB  - The Na(+), K(+)-ATPase are membrane-associated enzymes that transport Na(+) and
      K(+) across the membrane generating chemical and electrical gradients, essential
      to maintain the resting potential for the excitation of myocytons and neurons and
      for transport of nutrients. The cDNA encoding a full-length isoform of Taenia
      solium Na(+), K(+)-ATPase alpha-subunit (TNaK1alpha) was isolated from a
      cysticercal cDNA library. TNaK1alpha has 1014 amino acids and a predicted
      molecular mass of 111,989Da. The protein displays strong sequence homology and
      conserved motifs typical of Na(+), K(+)-ATPase alpha-subunits. Northern and
      Southern hybridizations reveal a TNaK1alpha mRNA of about 3.7kb, which is encoded
      by a single gene. Polyclonal antibodies raised against a synthetic peptide
      corresponding to the NH(2)-terminal sequence of TNaK1alpha recognized a 100-kDa
      polypeptide in the membrane fraction of adult and larval stages of T. solium and
      other Taenia species. Immunolocalization studies using the same antibodies
      revealed that the TNaK1 is preferentially localized in muscle cells and
      protonephridial ducts, and in small quantities in the tegument of T. solium
      cysticerci.

PMID- 15500919
TI  - Malaria infection induces a conformational change in erythrocyte band 3 protein.
AB  - Sequestration in the microvessels of the deep tissues is a signal characteristic
      of the human malaria Plasmodium falciparum. The adhesion of P. falciparum
      infected cells to the post-capillary endothelial cells in various tissues
      contributes to both the pathology of the disease (i.e. organ infarcts and coma)
      and parasite survival (i.e. the microaerophilic environment favors plasmodial
      growth while avoiding passage through and destruction in the spleen). This report
      identifies a conformational change in a region of band 3 protein involved in the
      enhanced adhesiveness of P. falciparum-infected erythrocytes.

PMID- 15500920
TI  - Characterisation of benzimidazole binding with recombinant tubulin from Giardia
      duodenalis, Encephalitozoon intestinalis, and Cryptosporidium parvum.
AB  - The binding kinetics of several benzimidazole compounds were determined with
      recombinant tubulin from benzimidazole-sensitive and -insensitive organisms. This
      study utilised the naturally occurring high efficacy of the benzimidazoles for
      the parasitic protozoa Giardia duodenalis and Encephalitozoon intestinalis, and
      low efficacy with Cryptosporidium parvum. Direct kinetic analysis of the
      benzimidazole-beta-tubulin interaction was performed using a fluorescence-based
      quenching method to determine the apparent association (k(on)) and dissociation
      (k(off)) rate constants from which the affinity constant (K(a)) was calculated.
      The binding kinetics were determined with recombinant alpha- and beta-tubulin
      from the parasitic protozoa with several benzimidazole R(2)-carbamate analogues.
      The affinity constant for the binding of several benzimidazoles with beta-tubulin
      from benzimidazole-sensitive protozoa was found to be significantly greater than
      binding to beta-tubulin from benzimidazole-insensitive protozoa. Additionally,
      the high affinity of several benzimidazole derivatives (albendazole,
      fenbendazole, mebendazole) for monomeric beta-tubulin and heterodimeric alphabeta
      tubulin from benzimidazole-sensitive protozoa was also clearly demonstrated. The
      affinity constants determined with beta-tubulin from G. duodenalis and E.
      intestinalis also supported the observed in vitro efficacy of these compounds.
      The binding characteristics of the benzimidazoles with the highest in vitro
      efficacy (albendazole, fenbendazole, mebendazole) was reflected in their high
      association and slow dissociation rates with the beta-tubulin monomer or dimer
      from benzimidazole-sensitive protozoa compared with insensitive ones.
      Benzimidazole-bound alphabeta-tubulin heterodimers also had a significantly lower
      rate of microtubule assembly compared with benzimidazole-free alphabeta
      heterodimers. The incorporation of benzimidazole-bound alphabeta-heterodimers
      into assembling microtubules was shown to arrest polymerisation in vitro although
      the addition of benzimidazole compounds to assembled microtubules did not result
      in depolymerisation. These findings indicate that a benzimidazole-beta-tubulin
      cap may be formed at the growing end of the microtubule and this cap prevents
      elongation of the microtubule.

PMID- 15500921
TI  - Shotgun optical mapping of the entire Leishmania major Friedlin genome.
AB  - Leishmania is a group of protozoan parasites which causes a broad spectrum of
      diseases resulting in widespread human suffering and death, as well as economic
      loss from the infection of some domestic animals and wildlife. To further
      understand the fundamental genomic architecture of this parasite, and to
      accelerate the on-going sequencing project, a whole-genome XbaI restriction map
      was constructed using the optical mapping system. This map supplemented
      traditional physical maps that were generated by fingerprinting and hybridization
      of cosmid and P1 clone libraries. Thirty-six optical map contigs were constructed
      for the corresponding known 36 chromosomes of the Leishmania major Friedlin
      genome. The chromosome sizes ranged from 326.9 to 2821.3 kb, with a total genome
      size of 34.7 Mb; the average XbaI restriction fragment was 25.3 kb, and ranged
      from 15.7 to 77.8 kb on a per chromosomes basis. Comparison between the optical
      maps and the in silico maps of sequence drawn from completed, nearly finished, or
      large sequence contigs showed that optical maps served several useful functions
      within the path to create finished sequence by: guiding aspects of the sequence
      assembly, identifying misassemblies, detection of cosmid or PAC clones
      misplacements to chromosomes, and validation of sequence stemming from varying
      degrees of finishing. Our results also showed the potential use of optical maps
      as a means to detect and characterize map segmental duplication within genomes.

PMID- 15500922
TI  - On the biogenesis of lipid bodies in ancient eukaryotes: synthesis of
      triacylglycerols by a Toxoplasma DGAT1-related enzyme.
AB  - In mammalian cells, the main stored neutral lipids are triacylglycerol and
      cholesteryl esters, which are produced by two related enzymes, acyl
      CoA:diacylglycerol acyltransferase (DGAT) and acyl-CoA:cholesterol
      acyltransferase (ACAT), respectively. Very little is known about the metabolism,
      intracellular storage and function of neutral lipids in many pathogenic lower
      eukaryotes. In this paper, we have characterized the activity of an important
      triacylglycerol synthetic enzyme in the protozoan Toxoplasma gondii. A full
      length cDNA and gene encoding a T. gondii DGAT1-related enzyme were identified
      and designated TgDGAT1. The gene is composed of 15 exons and 14 introns, and
      encodes a protein with a predicted M(r) 63.5kDa, containing signature motifs
      characteristic of the DGAT1 family. The native protein migrates at 44kDa under
      reducing conditions. TgDGAT1 is an integral membrane protein localized to the
      parasite cortical and perinuclear endoplasmic reticulum, with the C-terminus
      oriented to the lumen of the organelle. When a Saccharomyces cerevisiae mutant
      strain lacking neutral lipid production is transformed with TgDGAT1 cDNA, a
      significant DGAT activity is reconstituted, resulting in triacylglycerol
      synthesis and biogenesis of cytosolic lipid inclusions, resembling lipid bodies
      in T. gondii. No production of steryl esters is observed upon TgDGAT1 expression
      in yeast. In contrast to human DGAT1 lacking fatty acid specificity, TgDGAT1
      preferentially incorporates palmitate. Our results indicate that parasitic
      protozoa are also neutral lipid accumulators and illustrate the first example of
      the existence of a functional DGAT gene in an ancient eukaryote, demonstrating
      that diacylglycerol esterification is evolutionarily conserved.

PMID- 15500923
TI  - Structural analogs of sialic acid interfere with the binding of erythrocyte
      binding antigen-175 to glycophorin A, an interaction crucial for erythrocyte
      invasion by Plasmodium falciparum.
AB  - Plasmodium falciparum causes the most virulent form of malaria and remains a
      major worldwide health problem. The erythrocytic development of P. falciparum
      relies on parasite invasion of host erythrocytes, a process mediated in part by
      the interaction of erythrocyte binding antigen 175 (EBA-175) with the erythrocyte
      receptor glycophorin A (GA). The binding domain of EBA-175 that interacts with
      glycophorin A is a approximately 330 residues module called F2. Several studies
      have shown that F2 recognizes both sialic acids and the protein backbone on
      glycophorin A. Here, we have developed ELISA-based quantitative F2-GA binding
      assays. We also performed a series of competitive inhibition assays to block the
      F2-GA interaction using a variety of sialic acid analogs. Our data show that both
      2,3-didehydro-2-deoxy-N-acetyl neuraminic acid (DANA) and 3'-N-acetyl neuraminyl
      N-acetyl lactosamine are excellent inhibitors of the F2-GA interaction. Moderate
      levels of inhibition were also observed with monomers or oligomers of N-acetyl
      neuraminic acid (sialic acid). Furthermore, we show that DANA is able to
      significantly inhibit the invasion of erythrocytes by P. falciparum. Together,
      our ELISA-based binding assays and in vitro inhibition of erythrocyte invasion
      data suggest that small variations in the structures of DANA and related
      inhibitors can result in even more potent invasion inhibitory activities. Our
      studies provide a platform for the development of high potency inhibitors of the
      F2-GA interaction using high throughput drug discovery technologies. Such
      compounds may form part of inhibitor cocktails, which aim to block invasion of
      erythrocytes by P. falciparum.

PMID- 15500924
TI  - Chromosomal polymorphism, gene synteny and genome size in T. cruzi I and T. cruzi
      II groups.
AB  - Pulsed-field gel electrophoresis and DNA hybridization were used to establish and
      compare some parameters of the molecular karyotype of nine stocks classified into
      Trypanosoma cruzi I and T. cruzi II groups. The isolates showed a variable number
      of chromosomal bands (17-22) comprised between 0.4 and 3.3 Mbp. The total number
      of chromosomes and the genome size were estimated based on the fluorescence
      intensity of SYBR Green I-stained chromosomal bands. Differences in the length of
      the telomeric regions among the stocks and between chromosomes of the same stock
      were observed. No correlation was found between the length of the telomeric
      region and the group to which the isolate belongs. Hybridization of 54 genetic
      markers revealed extensive chromosome size polymorphism. Nevertheless, the most
      represented pattern was the hybridization of the probes in larger chromosomes in
      stocks of T. cruzi II as compared to T. cruzi I. Eight putative syntenic groups,
      encompassing 29 non-redundant genetic markers and distributed in 11 CL Brener
      chromosomal bands were disclosed. The syntenic groups were conserved in all the
      stocks. The relative abundance of repetitive DNA sequences was determined. C6,
      B11/L1Tc and E12 elements presented maximum 1.7-fold variation in copy number,
      whereas 195-bp satellite DNA (120,000 copies in Y strain) was four- to nine-fold
      more abundant in T. cruzi II stocks. The novel aspects of T. cruzi karyotype here
      presented contribute to the comprehension of the genome organization of this
      parasite and will assist the assignment of scaffold to the CL Brener chromosomal
      bands.

PMID- 15500925
TI  - Parasite genetics and the immune host: recombination between antigenic types of
      Eimeria maxima as an entree to the identification of protective antigens.
AB  - The genomes of protozoan parasites encode thousands of gene products and
      identification of the subset that stimulates a protective immune response is a
      daunting task. Most screens for vaccine candidates identify molecules by capacity
      to induce immune responses rather than protection. This paper describes the core
      findings of a strategy developed with the coccidial parasite Eimeria maxima to
      rationally identify loci within its genome that encode immunoprotective antigens.
      Our strategy uses a novel combination of parasite genetics, DNA fingerprinting,
      drug-resistance and strain-specific immunity and centres on two strains of E.
      maxima that each induce a lethal strain-specific protective immune response in
      the host and show a differential response to anti-Eimeria chemotherapy. Through
      classical mating studies with these strains we have demonstrated that loci
      encoding molecules stimulating strain-specific protective immunity or resistance
      to the anti-coccidial drug robenidine segregate independently. Furthermore,
      passage of populations of recombinant parasites in the face of killing in the
      immune host was accompanied by the elimination of some polymorphic DNA markers
      defining the parent strain used to immunise the host. Consideration of the
      numbers of parasites recombinant for the two traits implicates very few antigen
      encoding loci. Our data provide a potential strategy to identify putative antigen
      encoding loci in other parasites.

PMID- 15500926
TI  - Merozoite surface proteins 4 and 5 of Plasmodium knowlesi have differing cellular
      localisation and association with lipid rafts.

PMID- 15500927
TI  - Characterization of PfMyb1 transcription factor during erythrocytic development
      of 3D7 and F12 Plasmodium falciparum clones.

PMID- 15500928
TI  - Risk-benefit analysis of micronutrients.
AB  - Traditionally, different approaches have been used to determine the recommended
      dietary allowances for micronutrients, above which there is a low risk of
      deficiency, and safe upper levels, below which there is a negligible risk of
      toxicity. The advice given to risk managers has been in the form of point
      estimates, such as the recommended dietary allowance (RDA) and the tolerable
      upper level (UL). In future, the gap between the two intake-response curves may
      become narrower, as more sensitive indicators of deficiency and toxicity are
      used, and as health benefits above the recommended daily allowance are taken into
      account. This paper reviews the traditional approaches and proposes a novel
      approach to compare beneficial and adverse effects across intake levels. This
      model can provide advice for risk managers in a form that will allow the risk of
      deficiency or the risk of not experiencing the benefit to be weighed against the
      risk of toxicity. The model extends the approach used to estimate recommended
      dietary allowances to make it applicable to both beneficial and adverse effects
      and to extend the intake-incidence data to provide a range of estimates that can
      be considered by the risk manager. The data-requirements of the model are the
      incidence of a response at one or more levels of intake, and a suitable
      coefficient of variation to represent the person-to-person variations within the
      human population. A coefficient of variation of 10% or 15% has been used for
      established recommended dietary allowances and a value of 15% is proposed as
      default for considerations of benefit. A coefficient of variation of 45% is
      proposed as default for considerations of toxicity, based on analyses of human
      variability in the fate and effects of therapeutic drugs. Using this approach
      risk managers, working closely with risk assessors, will be able to define ranges
      of intake based on a balance between the risks of deficiency (or lack of benefit)
      and toxicity.

PMID- 15500929
TI  - Beverage caffeine intake in US consumers and subpopulations of interest:
      estimates from the Share of Intake Panel survey.
AB  - Concerns exist about the potential adverse health effects of high consumption of
      dietary caffeine, especially in children and pregnant women. Recommended caffeine
      intakes corresponding to no adverse health effects have been suggested recently
      for healthy adults (400-450 mg/day), for women contemplating pregnancy (300
      mg/day), and for young children age 4-6 years (45 mg/day). To determine whether
      current caffeine intake approaches these levels, intake from major dietary
      sources (coffee, tea and carbonated soft drinks) were measured in 10,712
      caffeinated beverage consumers in the 1999 US Share of Intake Panel, a targeted
      beverage survey. Mean caffeine intakes in adult caffeinated beverage consumers
      ranged from 106 to 170 mg/day (90th percentile intake was 227-382 mg/day). In
      children 1-5 and 6-9 years, mean caffeine intakes were 14 and 22 mg/day,
      respectively; corresponding 90th percentile intakes were 37 and 45 mg/day.
      Pregnant women consumed an average of 58 mg/day (157 mg/day at the 90th
      percentile), and women of reproductive age ingested 91-109 mg/day (229-247 mg/day
      at the 90th percentile). These data show that while mean caffeine intakes are
      within recommended safe levels, heavy consumers of certain subpopulations,
      including young children and women contemplating pregnancy, might benefit from
      dietary advice.

PMID- 15500930
TI  - DNA damage in leukocytes of mice treated with copper sulfate.
AB  - Single stranded DNA breaks induced by copper sulfate (CuSO(4)) in mice has been
      studied in vivo using Alkaline Single Cell Gel Electrophoresis (Comet assay).
      Mice were administered orally with doses of 0, 1.25, 2.50, 5.00, 7.50, 10.00 and
      12.50 mg/kg body weight (b.wt.) of CuSO4 respectively. The samples of whole blood
      were collected at 24, 48, 72 h, first week and second week post-treatment and the
      assay was carried out to determine single strand DNA breaks as represented by
      comet tail-length. In addition, the sample was used to study the repair
      efficiency by incubating the samples with RPMI medium for 2 h. Results indicated
      a significant DNA damage at all the doses after treatment with CuSO4 when
      compared to controls showing a clear dose-dependent response (p < 0.05). A
      gradual decrease in the tail-lengths from 48 h post-treatment was observed and by
      second week, the values returned to control levels at all doses. The study on the
      repair efficiency indicated that mice treated with all the doses of CuSO4 showed
      decrease in mean comet tail-length indicating repair efficiency capacity but less
      when compared to those of controls. The study also reveals that comet assay is a
      sensitive and rapid method for detecting DNA damage caused by trace metals such
      as copper (Cu).

PMID- 15500931
TI  - Differential effects of allyl sulfides from garlic essential oil on cell cycle
      regulation in human liver tumor cells.
AB  - In this study, diallyl sulfide (DAS), diallyl disulfide (DADS) and diallyl
      trisulfide (DATS), which are major organosulfur compounds (OSCs) of garlic, were
      used as experimental materials to investigate their modulation effects on cell
      viability and cell cycle in human liver tumor cells (J5). According to the
      results of cell viability assay, 50 or 100 microM DATS significantly decreased
      the cell viability as compared with the control (P < 0.05) in dose and time
      dependent relations. Phenomena of cell number loss, shape deformation and lysis
      were observed after treatment with 100 microM DATS for 24 h. Cell cycle studies
      showed that J5 cells were significantly arrested in G2/M phase as the cells were
      treated with 100 microM DADS, 10, 50 or 100 microM DATS for 24 h (P < 0.05). DATS
      was more effective in arresting cells in G2/M phase than DADS, and the phenomena
      of arresting J5 cells in G2/M phase increased obviously in dose and time
      dependent relations. According to the Western blot analysis, DATS decreased
      cyclin-dependent kinase (Cdks)-Cdk7 (i.e. Cdc2 activate kinase) protein levels in
      J5 cells but increased cyclin B1 protein level. The modulation potency to cyclin
      B1 and Cdk7 expressions was in the order of DATS > DADS > DAS. The modulation
      potency to cyclin B1 and Cdk7 protein levels increased with increasing in DATS
      concentration and culture time. In conclusion, DATS might affect cell viability
      and cell morphological changes in J5 cells and lead cells to be arrested in G2/M
      phase via controlling the expression of cyclin B1 and Cdk7 in J5 cells, and the
      controlling action might relate to the sulfuric atom numbers in the structures of
      all these allyl sulfides.

PMID- 15500932
TI  - Lack of carcinogenicity of enzymatically modified isoquercitrin in F344/DuCrj
      rats.
AB  - The present study was conducted to evaluate the potential carcinogenicity of
      enzymatically modified isoquercitrin, administered in the diet at doses of 0.5%
      or 1.5% to groups of 50 male and female F344/DuCrj rats. Control males and
      females (50 rats each) were maintained on basal diet. Animals were observed for
      104 weeks. There were no treatment-related clinical signs of toxicity in the
      treated groups. Body weights, feed consumption, survival rates and hematological
      findings for exposed rats of both sexes showed no variations among the groups.
      There was a slight but significant dose-dependent decrease in relative spleen
      weights in all treated groups, albeit with no histopathological variation.
      Overall histopathological evaluation of neoplasms and all tissues after 2 years
      showed that tumors developed in all groups including the controls. There was a
      non-significant tendency for increase in the incidence of pituitary gland
      adenomas in the high dose-treated females (45.5%) as compared to controls
      (27.7%), with a slight increase in hemorrhage incidences, but values for males
      were low and similar in both control and treated rats. There were no apparent
      effects of isoquercitrin on development of kidney neoplasms, hyperplasias or
      chronic nephropathy. Parathyroid adenomas or hyperplasias were found not affected
      by isoquercitrin treatment, and there were no differences in mammary gland
      fibroadenomas or hyperplasias between treated and control rats. Various tumors
      were found in other organs with no significant differences between the groups. In
      conclusion, under the conditions of this 2-year feeding experiment, no evidence
      was obtained of carcinogenicity of enzymatically modified isoquercitrin in male
      or female F344 rats.

PMID- 15500933
TI  - Effect of theophylline on L-alanine absorption in the rat jejunum.
AB  - The effect of theophylline on the accumulation of L-alanine (Ala) by the rat
      jejunum and the mechanism involved has been investigated. Ala is rapidly
      accumulated by the jejunal strips in vitro and saturation is reached between 10
      and 15 min. An In/Out ratio of 2.55 reflects the presence of an active component
      in the overall transport mechanism. Ala accumulation shows a tendency toward
      saturation as cellular Ala concentration increases. In the absence of Na+, Ala
      accumulation is reduced and a direct relationship is observed between alanine
      concentration in the incubation medium and its intracellular concentration.
      Alanine accumulation is inhibited when theophylline (TH) concentration in the
      incubation medium is greater than 0.5 mM. A maximum inhibition of approximately
      50% in the presence of 10 mM theophylline is observed. Further inhibition (57
      65%) is observed when the jejunal strips are incubated in a Na+-free medium
      containing 10 mM theophylline. Single-pass perfusion of the rat jejunum shows
      that the presence of 0.5 mM TH in the perfusate, simulating therapeutic doses,
      did not affect Ala absorption. However, about 55% inhibition of Ala absorption
      was observed when 10 mM TH was included in the perfusate. In conclusion, it could
      be stated that in both in vitro and in vivo studies high toxic but not
      therapeutic doses of TH inhibit intestinal Ala uptake. The mechanism of
      inhibition may be attributed to a non-carrier mediated mechanism with a minor
      effect noticed on Ala carrier system.

PMID- 15500934
TI  - Evaluation of the reproductive and developmental toxicity of the D-003, a mixture
      of long-chain fatty acids, in rats and rabbits.
AB  - D-003 is a mixture of long-chain fatty acids isolated and purified from sugar
      cane wax with cholesterol-lowering properties. D-003 given orally (500 and 1000
      mg/kg/day) to female rats for 15 days prior to mating, through mating and
      gestation to day 21 of lactation and male rats for 4 weeks prior and during
      mating did not induce toxic effects on reproduction. There were no significant
      reductions in the number of animals that conceived, in the numbers of pups born
      to those that did conceive, in the numbers of pups that survived until weaning,
      and in their body weights at weaning. Drug-treated and control groups' offspring
      were comparable in growth, physical and behavioral development, spontaneous
      activity and reproductive performance. Pregnant New Zealand rabbits were given D
      003 as oral doses of 500 and 1000 mg/kg/day on days 6 through 18 of gestation
      without any evidence of embryotoxicity or teratogenicity. The no-observed-effect
      dose in these two experimental studies was 1000 mg/kg/day. After assessment of
      the potential of high doses of D-003 to act on developing embryo and reproduction
      process, no evidence supports the conclusion that D-003 is a reproductive and
      developmental toxicant/teratogen.

PMID- 15500935
TI  - Inhibitory effects of Centella asiatica on azoxymethane-induced aberrant crypt
      focus formation and carcinogenesis in the intestines of F344 rats.
AB  - Effects of the water extract of Centella asiatica Linn. on formation of
      azoxymethane (AOM)-induced aberrant crypt foci (ACF) and intestinal tumorigenesis
      in male F344 rats were investigated. Treatment with the extract significantly
      decreased the number of larger ACF (with four or more crypts per focus) in the
      large intestine in the early stage, while the number of methylated DNA adducts
      was not decreased compared with that in the AOM-treated group. In the post
      initiation stage, the extract significantly decreased the total number of ACF and
      the number of larger ACF, accompanied by a decrease in the 5-bromo-2'
      deoxyuridine-labeling index and an increase in the induction of apoptotic cells
      in the colonic mucosa. The incidences of neoplasms, the numbers of
      adenocarcinomas in the small intestines and entire intestines, and sizes of
      neoplasms in the entire intestines in rats fed C. asiatica extract at a dose of
      10 mg/kg were smaller than those in rats given AOM alone (p < 0.05). The extract
      at a dose of 100 mg/kg significantly reduced the multiplicity of neoplasms in the
      small intestine (p < 0.05). These results suggest that inhibition of the
      formation of AOM-induced ACF by C. asiatica extract is associated with
      modification of cell proliferation and induction of apoptosis in colonic crypts
      and that the extract has a chemopreventive effect on colon tumorigenesis.

PMID- 15500936
TI  - Neoplastic and preneoplastic lesions induced by melamine in rat urothelium are
      modulated by dietary polyunsaturated fatty acids.
AB  - The modulatory effects of polyunsaturated fatty acids (PUFA) on urinary tract
      tumorigenesis of 275 Wistar rats were evaluated by treating animals with the
      tumorigenic agent melamine. Rats were fed with formulae containing 6% of 4
      varieties of fats: fish oil enriched in n-3 PUFA (FO), corn oil enriched in n-6
      (CO), olein containing mainly n-9 oleic acid (O), and 98% stearic acid (SA), the
      latter two being essential (EFA)-deficient inducers. Two commercially fed control
      groups with (CM) and without (C) melamine were used. Animals were autopsied at 22
      25 and at 36-40 weeks. Hepatic fatty acids showed that O and SA groups were EFA
      deficient. Simple well differentiated hyperplasias were significantly higher in
      the FO lot, whereas dysplasia was increased in the CO, O and SA lots. Most of the
      animals fed for 36-40 weeks with the three latter formulae developed the more
      severe lesions. Increased urothelial proliferation was more frequent in EFA
      deficient rats. The apoptosis/mitosis ratio was higher in O, SA and CO fed
      animals with respect to FO and chow ones. Results show that dietary PUFA modulate
      differentially both normal and pre-neoplastic urothelial proliferation induced by
      melamine. FO, rich in n-3 fatty acids, showed a strong protective effect.

PMID- 15500937
TI  - Protective effect of gamma-aminobutyric acid against glycerol-induced acute renal
      failure in rats.
AB  - To investigate the effect of gamma-aminobutyric acid (GABA) on acute renal
      failure, we used a rat model of acute tubular necrosis induced by glycerol. After
      deprivation of water for 6h, the rats received an injection of 50% glycerol into
      the muscle of the rear limb at 10 ml/kg body weight. GABA was then administered
      orally to the rats (100 or 500 mg/kg body weight/day) once every 12h for 3 days.
      The rats with acute renal failure showed arrested body weight gain and an
      increase of kidney weight, whereas oral administration of GABA attenuated the
      physiological changes induced by acute renal failure. However, GABA
      administration had no significant effect on increased urine volume. Oral
      administration of GABA at a dose of 100 or 500 mg/kg body weight/day for 3 days
      significantly improved the markedly elevated levels of blood urea nitrogen and
      creatinine and the reduced creatinine clearance related to progression of renal
      failure. Moreover, the rats with acute renal failure exhibited high levels of
      fractional excretion of sodium (FE(Na)) due to alteration of tubule function
      following injection of glycerol. However, administration of GABA lowered the
      FE(Na) levels dose-dependently. Furthermore, urine osmolarity was markedly
      reduced in control rats with acute renal failure as compared with normal rats,
      whereas it was significantly increased by administration of GABA at a dose of 500
      mg/kg body weight/day. These results indicate that GABA has potential as a
      therapeutic agent against the renal damage involved in acute renal failure.

PMID- 15500938
TI  - Evaluation of the anti-proliferative and anti-oxidative activities of leaf
      extract from in vivo and in vitro raised Ashwagandha.
AB  - Withania somnifera (Ashwagandha) is used in Indian traditional medicine, Ayurveda
      and is believed to have a variety of health promoting effects. Molecular
      mechanisms and pathways underlying these effects have not been studied. We tried
      to characterize various activities of leaf extract of Ashwagandha (Lash) raised
      in the field and in the laboratory. We found that the Lash from field-raised
      plants has a significant anti-proliferative activity in human tumorigenic cells.
      However, it did not impart any protection against the oxidative damage caused by
      high glucose and hydrogen peroxide to human tumor cells suggesting that it can be
      used as an anti-tumor, but not as an anti-oxidant, substance.

PMID- 15500939
TI  - Application of simplified in vitro screening tests to detect genotoxicity of
      aristolochic acid.
AB  - Aristolochic acid (AA), the active compound found in Aristolochia extracts, has
      been used as a traditional medicine. However, products containing AA were
      withdrawn from the market in the early 1980s because AA was found to be a potent
      carcinogen. Some genotoxicity studies of AA were conducted after the
      carcinogenicity of AA was reported. The purpose of this study was to check the
      ability of simplified, screening tests for genotoxicity to indicate the genotoxic
      activities of AA. Four commonly used in vitro genotoxicity endpoints were
      examined. In a bacterial mutation screening test, AA was mutagenic to tester
      strains TA98 and TA100 with and without rat liver S9. In the L5178Y mouse
      lymphoma cell gene mutation test, mutagenic activity was observed at > or = 25
      microg/ml with or without S9. A concentration-dependent increase in structural
      chromosome aberrations was observed in CHO cells, with significant increases at
      50 microg/ml without S9 and at 25 microg/ml with S9. Significant increases in
      micronucleated binucleated cells were observed in CHO cells treated with AA at >
      or = 25 microg/ml with or without S9. These results demonstrated that the
      genotoxicity of AA would have been easily detected if simple screening versions
      of in vitro genotoxicity assays had been used during early product development.
      It is suggested that simplified screening tests such as those used in this study
      would be a rapid and economical way of obtaining the preliminary genotoxicity
      profiles of new substances or products as an aid to decision-making for further
      development.

PMID- 15500940
TI  - A randomized, double-blinded, placebo-controlled oral challenge study to evaluate
      the allergenicity of commercial, food-grade fish gelatin.
AB  - BACKGROUND: Recent interest in the labeling of foods and food proteins derived
      from allergenic sources necessitates determination of the potential allergenicity
      of such food ingredients. Fish gelatin is extracted from the skin of fish species
      known to elicit allergic reactions in sensitized individuals. OBJECTIVE: To
      determine the allergenicity of fish gelatin by double-blinded, placebo-controlled
      food challenges (DBPCFC) in clinically fish-allergic individuals. METHODS: Thirty
      fish-allergic patients diagnosed according to the EAACI Guidelines were included
      (age 9-50 years). Skin prick tests (SPT) and Histamine Release tests (HR) were
      performed with fish gelatin and codfish, and codfish-specific IgE was measured.
      All patients underwent DBPCFC with a cumulative dose of 14.61 g fish gelatin.
      RESULTS: In all 30 patients SPT, HR, and specific IgE to codfish were positive.
      SPT and HR with fish gelatin were positive in 3/30 and 7/30, respectively. One
      patient showed mild reaction to placebo and no reaction to the active challenge.
      Two patients reported mild subjective reactions to active challenge. Upon re
      challenge one of them described subjective symptoms again to the active challenge
      (7.61 g cumulated dose of fish gelatin) with no reaction to placebo, while the
      other experienced very mild subjective symptoms to placebo and nothing to the
      active. The proportion of truly sensitive patients was estimated to 0.03 in the
      total study group. CONCLUSION: None of 30 fish allergic patients reacted
      adversely to the ingestion of 3.61 g cumulative dose of fish gelatin. In this
      study fish gelatin presents no risk to fish-allergic patients at the doses
      typically used. Statistically, these results indicate that there is 95% certainty
      that 90% of fish-allergic consumers will not react to ingestion of a 3.61 g
      cumulative dose of fish gelatin.

PMID- 15500941
TI  - Antioxidant properties of black tea in alcohol intoxication.
AB  - Food ingredients such as alcohol may modify cellular redox state. Ethanol
      metabolism is accompanied by generation of free radicals that can damage cell
      components especially when antioxidant mechanisms are no able to neutralize them.
      However black tea is a source of polyphenol antioxidants that may enhance
      cellular antioxidant abilities. The aim of this study was to investigate the
      effect of black tea on antioxidant abilities of the liver, blood serum and brain
      of 12-months old rats sub-chronically (for 28 days) intoxicated with ethanol.
      Administration of black tea alone caused increase in the activity and
      concentration of antioxidant parameters more extensively in the liver and serum
      than in the brain. Alcohol caused decrease in the liver glutathione peroxidase
      and reductase and catalase activity but increase in activity of superoxide
      dismutase. Moreover, decrease in the level of non-enzymatic antioxidants, such as
      reduced glutathione, vitamin C, A and E and beta-carotene was observed. The
      activity of serum glutathione peroxidase and reductase decreased while superoxide
      dismutase activity was not changed. The level of non-enzymatic antioxidants in
      serum was also decreased. However brain activity/level of all examined
      antioxidants enzymatic as well as non-enzymatic was decreased after ethanol
      intoxication. Black tea considerably prevented antioxidant parameters against
      changes caused by ethanol. These results indicate beneficial antioxidant effect
      of black tea regarding all examined tissues, but especially the liver.

PMID- 15500942
TI  - Toxicity of copper intake: lipid profile, oxidative stress and susceptibility to
      renal dysfunction.
AB  - The present study was carried out to investigate the effects of copper (Cu)
      intake on lipid profile, oxidative stress and tissue damage in normal and in
      diabetic condition. Since diabetes mellitus is a situation of high-risk
      susceptibility to toxic compounds, we examined potential early markers of Cu
      excess in diabetic animals. Male Wistar rats, at 60-days-old were divided into
      six groups of eight rats each. The control(C) received saline from gastric tube,
      the no-diabetic(Cu-10), treated with 10 mg/kg of Cu(Cu(++)-CuSO4, gastric tube),
      no-diabetic with Cu-60 mg/kg(Cu-60), diabetic(D), diabetic low-Cu(DCu-10) and
      diabetic high-Cu(DCu-60). Diabetes was induced by an ip injection of
      streptozotocin (60 mg/kg). After 30 days of treatments, no changes were observed
      in serum lactate dehydrogenase, alanine transaminase and alkaline phosphatase,
      indicating no adverse effects on cardiac and hepatic tissues. D-rats had glucose
      intolerance and dyslipidemic profile. Cholesterol and LDL-cholesterol were higher
      in Cu-60 and DCu-60 than in C, Cu-10 and D and DCu-10 groups respectively. Cu-60
      rats had higher lipid hydroperoxide (HP) and lower superoxide dismutase (SOD) and
      glutathione peroxidase (GSH-Px) serum activities than C and Cu-10 rats. LH was
      increased and GSH-Px was decreased, while no alterations were observed in SOD and
      catalase in serum of DCu-60 animals. DCu-60 rats had increased urinary glucose,
      creatinine and albumin. In conclusion, Cu intake at high concentration induced
      adverse effects on lipid profile, associated with oxidative stress and diminished
      activities of antioxidant enzymes. Diabetic animals were more susceptible to
      copper toxicity. High Cu intake induced dyslipidemic profile, oxidative stress
      and kidney dysfunction in diabetic condition. Copper renal toxicity was
      associated with oxidative stress and reduction at least, one of the antioxidant
      enzymes.

PMID- 15500943
TI  - E1AF, an ets-oncogene family transcription factor.
AB  - E1AF is an ets-oncogene family transcription factor. E1AF was shown to upregulate
      multiple matrix metalloproteinase (MMP) genes and contribute to the malignant
      phenotype of cancer cells by inducing invasive and metastatic activities. E1AF is
      upregulated by hepatocyte growth factor (HGF) stimulation, which indicates that
      E1AF would participate in cell motility by HGF/scatter factor. On the other hand,
      E1AF upregulates p21waf1/cip1 to induce cell cycle arrest when cells are exposed
      to stress. EWS/ETS fusions are frequently observed in Ewing's sarcoma, and we
      have revealed that EWS/ETS chimeric protein activates telomerase activity by
      upregulating hTERT. However, substitution ets binding site (EBS) mutants did not
      affect the responsiveness to EWS/E1AF. DNA-IP assay showed that the complexes
      contained EWS/E1AF bound to the hTERT promoter, which suggested that EWS/ETS
      functions as a co-activator for TERT transcription. Our findings that EWS/ETS
      acts as a transcriptional co-factor may imply that the transcription pathway is
      regulated by the interaction of transcription factors.

PMID- 15500944
TI  - Ganoderma lucidum extracts inhibit growth and induce actin polymerization in
      bladder cancer cells in vitro.
AB  - This study was conducted to investigate chemopreventive effects of Ganoderma
      lucidum using a unique in vitro human urothelial cell (HUC) model consisted of
      HUC-PC cells and MTC-11 cells. Ethanol and water extracts of fruiting bodies and
      spores of the G. lucidum were used to examine growth inhibition, actin
      polymerization status, and impact of actin remodeling on cell migration and
      adhesion. Results showed that ethanol extracts had a stronger growth inhibition
      effect than water extracts. Cell cycle analysis showed that the growth inhibition
      effect was associated with G2/M arrest. At non-cytotoxic concentrations (40-80
      microg/ml), these extracts induced actin polymerization, which in turn inhibited
      carcinogen 4-aminobiphenyl induced migration in both cell lines. The increased
      actin polymerization was associated with increased stress fibers and focal
      adhesion complex formation, however, expression of matrix metalloproteinase-2 and
      focal adhesion kinase (total and phospholated) were unchanged, which suggests
      that other mechanisms may be involved.

PMID- 15500945
TI  - Boric acid inhibits human prostate cancer cell proliferation.
AB  - The role of boron in biology includes coordinated regulation of gene expression
      in mixed bacterial populations and the growth and proliferation of higher plants
      and lower animals. Here we report that boric acid, the dominant form of boron in
      plasma, inhibits the proliferation of prostate cancer cell lines, DU-145 and
      LNCaP, in a dose-dependent manner. Non-tumorigenic prostate cell lines, PWR-1E
      and RWPE-1, and the cancer line PC-3 were also inhibited, but required
      concentrations higher than observed human blood levels. Studies using DU-145
      cells showed that boric acid induced a cell death-independent proliferative
      inhibition, with little effect on cell cycle stage distribution and mitochondrial
      function.

PMID- 15500946
TI  - Exhaustive physical exercise increases the number of colonic preneoplastic
      lesions in untrained rats treated with a chemical carcinogen.
AB  - Aberrant crypt foci (ACF) have been used for early detection of factors that
      influence colorectal carcinogenesis in rats. It has been observed that exhaustive
      exercise increases free radical DNA oxidative damage and depresses immune
      function, events also related to the increased risk for cancer development.
      Fifteen days after a single exhaustive swimming bout in untrained rats treated
      with a colon carcinogen, we observed a statistically significant increased number
      of ACF when compared to the non-exercised group. Thus, we concluded that
      exhaustive exercise increased the susceptibility for colon cancer in rats. From
      our finding and literature data, we hypothesize that, similarly to the suggested
      relationship between exercise and infections, exercise could be protective
      against cancer or it could increase the risk for this disease depending on its
      type, dose and duration.

PMID- 15500947
TI  - Anti-tumor angiogenesis effect of aminopeptidase inhibitor bestatin against B16
      BL6 melanoma cells orthotopically implanted into syngeneic mice.
AB  - We investigated the effect of bestatin, an inhibitor of aminopeptidase N
      (APN)/CD13 and aminopeptidase B, on the angiogenesis induced by B16-BL6 melanoma
      cells. Oral administration of bestatin (100-200 mg/kg/day) was found to
      significantly inhibit the melanoma cell-induced angiogenesis in a mouse dorsal
      air sac assay. Additionally, anti-APN/CD13 mAb (WM15), which neutralizes the
      aminopeptidase activity in tumor cells, as well as bestatin inhibited the tube
      like formation of human umbilical vein endothelial cells (HUVECs) in vitro.
      Furthermore, the intraperitoneal administration of bestatin (50-100 mg/kg/day)
      after the orthotopic implantation of B16-BL6 melanoma cells into mice reduced the
      number of vessels oriented towards the established primary tumor mass on the
      dorsal side of mice. These findings suggest that bestatin is an active anti
      angiogenic agent that may inhibit tumor angiogenesis in vivo and tube-like
      formation of endothelial cells in vitro through its inhibition of APN/CD13
      activity.

PMID- 15500948
TI  - Hematoporphyrin monomethyl ether photodynamic damage on HeLa cells by means of
      reactive oxygen species production and cytosolic free calcium concentration
      elevation.
AB  - Hematoporphyrin monomethyl ether (HMME) is a novel and promising porphyrin
      related photosensitizer for photodynamic therapy (PDT). HMME-PDT-induced cell
      death and its mechanisms were investigated in HeLa cells. We demonstrated that
      HMME-PDT could induce cell death through both necrosis and apoptosis. Sodium
      azide (the singlet oxygen quencher) or D-mannitol (the hydroxyl radical
      scavenger) could protect HeLa cells from the apoptosis and necrosis induced by
      HMME-PDT, showing that reactive oxygen species (ROS), such as singlet oxygen and
      hydroxyl radical, played a decisive role in HMME-PDT-induced HeLa cells death.
      Sodium azide or D-mannitol also inhibited HMME-PDT-mediated [Ca2+]i elevation.
      Cytochrome C (Cyto C) release from mitochondria into cytosol and Caspase-3
      activation after HMME-PDT were inhibited by BAPTA/AM (an intracellular calcium
      chelator). These results demonstrated that ROS generated in HeLa cells by HMME
      PDT-induced apoptosis may be through [Ca2+]i elevation which mediates Cyto C
      release and Caspase-3 activition and initiates the subsequent late stages of
      apoptosis.

PMID- 15500949
TI  - The clinical features of rectal cancers with high-frequency microsatellite
      instability (MSI-H) in Japanese males.
AB  - Colorectal cancers with high-frequency microsatellite instability (MSI-H) are
      known to display striking differences in their clinical and pathological features
      compared to microsatellite stable (MSS) cancers. Previous studies revealed that
      MSI-H cancers are more likely to occur in women, irrespective of the higher
      incidence of colorectal cancer in men. In this study we investigated the gender
      specific clinico-pathological features of MSI positive colorectal cancer in
      Japanese individuals. A series of 478 colorectal carcinomas were collected in an
      unbiased manner and analyzed for microsatellite instability status. Seven
      percent, 6% and 87% of tumors showed MSI-H, low-frequency microsatellite
      instability (MSI-L) and MSS, respectively. A comparison of gender indicated a
      statistical significance in terms of the distribution of the subsite and age of
      onset of MSI-H colorectal cancer. In general, MSI-H cancers prone to develop in
      the proximal colon however, we found that about 36% of MSI-H cancers in men
      developed in the rectum. These rectal cancers were more likely to have a mucinous
      component and multiple colorectal cancers including critical lesion. These
      findings should be useful to find MSI positive rectum cancer.

PMID- 15500950
TI  - RNA expression of human telomerase subunits TR and TERT is differentially
      affected by melatonin receptor agonists in the MCF-7 tumor cell line.
AB  - The RNA expression levels of human catalytic subunit (TERT) and the RNA subunit
      (TR) of telomerase were analysed after treatment with the agonists of the
      membrane receptor (S 20098) and the nuclear receptor (CGP 52608) for melatonin in
      the MCF-7 human breast tumor cell line. Neither membrane nor nuclear signalling
      affected the RNA steady-state levels of the TR subunit of telomerase. On the
      contrary, we observed a significant decreased in the RNA levels of TERT after
      treatment with CGP 52608 while S 20098 produced a significant increase in the RNA
      levels of TERT. These results support a cross-talk between membrane and nuclear
      melatonin signalling and provide new data on the hormonal regulation of
      telomerase function.

PMID- 15500951
TI  - Tankyrase, a positive regulator of telomere elongation, is over expressed in
      human breast cancer.
AB  - Tankyrase promotes telomere elongation by interaction with the telomeric protein
      binding factor TRF1, a negative regulator of telomere extension. We measured
      tankyrase mRNA by real-time RT-PCR in 66 breast cancers and in paired normal
      tissues. Results were compared with hTERT mRNA expression. The levels of
      tankyrase in breast cancers were significantly higher in comparison to normal
      tissues (P<0.0001) and significantly related to the status of progesterone
      receptors. No relationship was found between tankyrase and hTERT mRNA expression
      in breast cancers. According to our results, tankyrase expression appeared up
      regulated in breast cancers.

PMID- 15500952
TI  - GSTP1 affects chemoresistance against camptothecin in human lung adenocarcinoma
      cells.
AB  - Glutathione S-transferase P1 (GSTP1) is known as a xenobiotic enzyme through
      conjugation of glutathione and also as an inhibitor of Jun N-terminal kinase
      (JNK). We intended to investigate whether GSTP1 affects chemoresistance against
      camptothecin in human lung adenocarcinoma cells. Camptothecin induced GSTP1
      expression. Downregulation of GSTP1 increased necrosis induced by camptothecin in
      A549 cells but not in PC-14 and RERF-LC-KJ cells. This phenomenon in A549 cells
      was hardly changed by JNK inhibitor SP600125 but was almost diminished by l
      buthionine-sulfoximine. These results suggest that GSTP1 has protective effects
      against camptothecin-induced necrosis in subset of human lung adenocarcinoma
      through glutathione conjugation.

PMID- 15500953
TI  - Serum levels of angiogenic cytokines decrease after antineoplastic radiotherapy.
AB  - Serum levels of angiogenic cytokines decrease after radiotherapy in patients with
      cancer and their may have an impact on response to treatment and progression-free
      survival. Here, we have evaluated sera of patients before and after radiotherapy
      for various tumour types for levels of soluble fibroblast growth factor-2 (FGF
      2), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF)
      to assess whether these factors decrease after radiotherapy, and whether their
      diminution is related to the radiation dose, tumour type, age and haemoglobin
      level. We demonstrate that levels of FGF-2 and VEGF, but not HGF, decrease
      significantly, and that the extent of their diminution is related to the
      radiation dose and response.

PMID- 15500954
TI  - High expression of endothelial cell nitric oxide synthase in peritumoral
      microvessels predicts increased disease-free survival in colorectal cancer.
AB  - We have previously shown that a high frequency of microvessels expressing
      endothelial cell nitric oxide synthase (ecNOS) in the area surrounding the
      primary tumor (peritumoral ecNOS-expressing microvessel density: PEMVD) is a
      favorable prognostic indicator in breast cancer. Studies of a retrospective
      material of 186 colorectal tumors (Duke's stage B) now show that PEMVD is a
      significant and independent prognostic indicator for disease-free survival also
      in these patients. These data reinforce our hypothesis that a high level of
      expression of ecNOS in microvessels in the tumor-adjacent area protects against
      tumor metastasis.

PMID- 15500955
TI  - Prognostic significance of intra-tumoral estradiol level in breast cancer
      patients.
AB  - Although the intra-tumoral estradiol (E2) level is thought to be more closely
      related to the E2-inducible events such as progesterone receptor (PR) induction
      and tumor growth than the serum E2 level, prognostic significance of the intra
      tumoral E2 level in breast cancer patients has yet to be studied. E2 level in
      tumor tissues obtained from 90 primary breast cancer patients were measured by
      the high-pressure liquid chromatography-radioimmunoassay method. Relationship
      between the intra-tumoral E2 level and the various clinicopathological factors
      including the prognosis was investigated. E2-high tumors (n=45) were
      significantly more likely to be estrogen receptor (ER)-positive tumors and PR
      positive tumors than E2-low tumors (n=45). A significant correlation was observed
      between the intra-tumoral E2 level and PR level by a simple curve fit test
      (r=0.39, P<0.01) in the ER-positive tumors. Univariate analysis showed that lymph
      node status, intra-tumoral E2 level, ER, and PR were significant prognostic
      factors, and multivariate analysis showed that only lymph node status and PR
      status were significant independent prognostic factors. PR is induced by E2
      through ER in human breast cancers. PR, which warrants both the presence of
      functional ER and the enough level of intra-tumoral E2, can serve as a better
      prognostic factor than intra-tumoral E2 level or ER in primary breast cancer
      patients probably because PR is a better marker of estrogen-dependency of tumor
      growth than intra-tumoral E2 level or ER.

PMID- 15500956
TI  - Protective effects on neuronal cells of mouse afforded by ebselen against
      oxidative stress at multiple steps.
AB  - Ebselen (2-phenyl-1,2-benzisoselenazol-3[2H]-one) mimics the activity of
      glutathione peroxidase [Biochem. Pharmacol. 33 (1984) 3235], acts as a substrate
      for thioredoxin reductase [Proc. Natl. Acad. Sci. U.S.A. 99 (2002) 8579]. The
      present study focused on the cellular mechanism of its action against oxidative
      stress by using HT22 cells, a mouse neuroblastoma of hippocampal origin. Ebselen
      protected HT22 cells against death induced by glutamate and hydrogen peroxide but
      not against that by tumor necrosis factor alpha. Oxidative glutamate toxicity is
      initiated by depletion of total glutathione, and ebselen inhibited the decrease
      in glutathione and increased its basal level. Although glutamate increased
      intracellular levels of reactive oxygen species (ROS), ebselen suppressed their
      increase. Ebselen reduced the basal levels of ROS when it was applied in control
      cells. Ebselen also removed ROS from cells that had accumulated a level of them.
      The compound had a significant trolox equivalent activity concentration value in
      a cell-free system, suggesting that it has a direct ROS-scavenging capacity.
      Finally, ebselen-induced heme oxygenase-1 (HO-1) protein. These results indicate
      that ebselen protects neuronal cells against the oxidative stress at multiple
      steps, including an increase in glutathione, a ROS-scavenging activity and the
      induction of HO-1 protein.

PMID- 15500957
TI  - Insulin degrading enzyme is expressed in the human cerebrovascular endothelium
      and in cultured human cerebrovascular endothelial cells.
AB  - Insulin degrading enzyme (IDE) is found in the cytosol, peroxisomes and plasma
      membrane of many cells. Although it preferentially cleaves insulin it can also
      cleave many other small proteins with diverse sequences including the monomeric
      form of the amyloid beta peptide (A beta). In the brain, IDE has been reported to
      be expressed predominantly in neurons. In this study, IDE expression was detected
      in cultured human cerebrovascular endothelial cells. Using laser capture
      microdissection followed by PCR analysis, it was found that IDE mRNA is expressed
      in human brain blood vessels. Using immunofluorescence and multiphoton microscopy
      IDE was localized to the endothelium of the cerebrovascular blood vessels in
      human.

PMID- 15500958
TI  - Zaprinast stimulates extracellular adenosine accumulation in rat pontine slices.
AB  - Adenosine appears to be an endogenous somnogen. The lateral dorsal
      tegmental/pedunculopontine nucleus (LDT/PPT) located in the mesopontine tegmentum
      is important in the regulation of arousal. Neurons in this nucleus are strongly
      hyperpolarized by adenosine and express neuronal nitric oxide synthase. Zaprinast
      is a cyclic nucleotide phosphodiesterase inhibitor, and has been shown in the
      hippocampal slice to inhibit the field excitatory postsynaptic potential. This
      action could be blocked by an adenosine receptor antagonist, and therefore is
      presumably due to adenosine release stimulated by zaprinast. In the present study
      we tested the effect of zaprinast on extracellular adenosine accumulation in
      pontine slices containing the LDT. Zaprinast at 10 microM evoked an increase in
      extracellular adenosine concentration. This effect was blocked by impermeant
      inhibitors of 5'-nucleotidase, indicating that the extracellular adenosine was
      derived from extracellular AMP. However, inhibitors of cAMP degradation had
      little or no effect on zaprinast-evoked adenosine accumulation, suggesting that
      extracellular cAMP was not the source. Removal of extracellular calcium inhibited
      the effect of zaprinast. These results demonstrate that a pathway exists by which
      zaprinast stimulates extracellular adenosine accumulation, and the presence of
      this pathway in the pontine slice suggests the possibility that it may be
      relevant for the regulation of behavioral state.

PMID- 15500959
TI  - Perceptual learning modulates electrophysiological and psychophysical response to
      visual texture segmentation in humans.
AB  - We investigated the mechanisms that allow, via perceptual learning, selective
      modulation of a visual line-texture figure saliency in accordance with task
      relevance. Learning-dependent saliency increase was inferred by increased
      accuracy in orientation discrimination with task repetition. As a result of
      learning, accuracy increase was more pronounced when local and global orientation
      of the texture figure conflicted, and reached ceiling in both conflict and
      conflict-free conditions. This psychophysical effect was associated with a
      decrease in amplitude of negative VEP components in the configurations where
      global and local orientation conflicted, and to a weak increase of VEP's earliest
      negative component in the conflict-free condition. The VEP result is a direct
      demonstration that learning, in addition to increasing response of relevant
      channels, also reduces the weight of channels whose receptive field size and
      orientation tuning conflict with the task.

PMID- 15500960
TI  - The ultrastructural localisation of the N-methyl-D-aspartate NR2B receptor
      subunit in rat lumbar spinal cord.
AB  - Glutamate together with its N-methyl-d-aspartate (NMDA) receptors has an
      important role in the transmission of stimuli in the spinal cord. Whilst the
      expression of the various NMDA receptor subunits within the spinal cord has been
      investigated the subcellular location of the NMDA NR2B subunit has yet to be
      definitively established. Both mRNA and light microscopical studies have failed
      to unequivocally demonstrate the proposed pre-synaptic location of this subunit.
      This has been proposed from pharmacological data and is thought to underlie the
      apparent analgesic properties of selective NR2B antagonists. Using pre-embedding
      immunohistochemistry combined with electron microscopy our findings provide the
      first definitive morphological evidence for both a pre- and post-synaptic
      localisation of NR2B/containing NMDA receptors, and suggest expression by
      astrocytes, in the rat lumbar spinal cord.

PMID- 15500961
TI  - Monoamines directly inhibit N-methyl-D-aspartate receptors expressed in Xenopus
      oocytes in a voltage-dependent manner.
AB  - Dopamine has numerous functions in the brain and has been shown to modulate
      responses of N-methyl-D-aspartate (NMDA) receptors on thalamic and hippocampus
      neurons [N.G. Castro, M.C.F. de Mello, F.G. de Mello, Y. Aracava, Direct
      inhibition of the N-methyl-D-aspartate receptor channel by dopamine and (+)
      SKF38393, Br. J. Pharmacol. 126 (1999) 1847-1855]. Thus, the effects of dopamine,
      serotonin, tyramine, epinephrine, norepinephrine, and octopamine on NMDA
      receptors were studied using voltage-clamp recording of recombinant NMDA
      receptors expressed in Xenopus oocytes. Serotonin and tyramine, in addition to
      dopamine, were found to inhibit macroscopic currents at heteromeric NMDA
      receptors, but not AMPA (GluR1/GluR2) receptors. Epinephrine, norepinephrine and
      octopamine also weakly inhibited macroscopic currents at NR1/NR2A and NR1/NR2B
      receptors. The inhibitory effects of these monoamines became prominent at -100 mV
      comparing those at -20 mV. Mutations at NR1 N616, NR2B N615, and NR2B N616, but
      not at NR1 W563 and NR1 N650, reduced the inhibitory effects by monoamines. These
      results indicate that these monoamines directly act on the narrowest region of
      channel pore.

PMID- 15500962
TI  - D3 dopamine receptor activates phospholipase D through a pertussis toxin
      insensitive pathway.
AB  - Within the dopamine receptor family, the D(3) dopamine receptor's function
      remains inadequately described. The D(3) receptor has been shown to couple to
      inhibition of adenylyl cyclase, stimulation of mitogenesis, and regulation of
      K(+) and Ca(2+) currents, all in a pertussis toxin (PTX)-sensitive manner. Here
      we report D(3) receptor activation of the phospholipase D (PLD) enzyme in HEK 293
      cells heterologously expressing the human D(3) receptor. Activation by agonist is
      dose dependent and displays the pharmacology expected of the D(3) receptor. The
      D(3) receptor specific antagonists AJ-76 and U99194A ablated the increase in
      activity by the preferring D(3) agonist (+) 7-OH DPAT. In addition, the D(3)
      receptor-mediated activation of PLD is not mediated by G-proteins of the
      G(i)/G(o) family, as pretreatment with PTX had no effect. PLD activation is a
      novel finding for the D(3) receptor, and is the first example of an effector
      system where D(3) signals without G(i)/G(o) protein intermediates.

PMID- 15500963
TI  - Attenuation of fasting-induced phosphorylation of mitogen-activated protein
      kinases (ERK/p38) in the mouse hypothalamus in response to refeeding.
AB  - Nutritional status modify the expression of hypothalamic neuropeptides through
      various signal molecules, including mitogen-activated protein kinases (MAPKs) and
      cAMP/calcium-responsive element-binding protein (CREB), for the regulation of
      energy balance. Previously, we demonstrated fasting-induced activation of
      extracellular signal-regulated kinase 1/2 (ERK) and p38 mitogen-activated protein
      kinase (p38) in the murine hypothalamus. To study how caloric intake after food
      deprivation influences intracellular signal transduction, we investigated the
      phosphorylation of ERK and p38 in the murine hypothalamus of refed mice. In the
      arcuate nucleus, refeeding significantly attenuated fasting-induced
      phosphorylation of ERK and CREB. In the paraventricular nucleus, fasting-induced
      phosphorylation of ERK and p38 was also significantly decreased by refeeding.
      Thus, refeeding rapidly reduced the fasting-induced phosphorylation of ERK, p38,
      and CREB, suggesting that the activation of these signal molecules in the
      hypothalamus is precisely regulated with feeding status.

PMID- 15500964
TI  - Effects of kindling and irradiation on neuronal density in the rat dentate gyrus.
AB  - Low-dose radiosurgery is presently in use as a treatment modality for focal
      epilepsy, but the mechanisms underlying the associated changes in seizure
      expression are poorly understood. We investigated whether total and parvalbumin
      expressing (PV+) neuronal densities within the hippocampus and amygdala are
      affected by analogous focal irradiation in amygdala-kindled rats. Adult rats were
      kindled by electrical stimulation through 10 stage 5 seizures. The kindled
      amygdala was then focally irradiated at 18 or 25 Gy, and generalized seizure
      thresholds were subsequently monitored for approximately 6 months. Histological
      and immunohistochemical assays of total and PV+ neuronal densities were performed
      bilaterally throughout the hippocampus and within the basolateral amygdala. PV+
      neuronal densities were unaffected by kindling or irradiation in these regions.
      Kindling selectively reduced neuronal densities in the dentate granule cell
      layer, and medial CA3 pyramidal cell layer. Irradiation at 25 Gy, but not at 18
      Gy, prevented or reversed this kindling-associated reduction in density.

PMID- 15500965
TI  - Binocular rivalry is partly resolved at early processing stages with steady and
      with flickering presentation: a human event-related brain potential study.
AB  - When their two eyes are presented with radically different images, observers
      report a fluctuation in perception between those images. This phenomenon, i.e.
      that only one image dominates the percept at a time, is termed binocular rivalry.
      Consequently, when rivalrous stimulation is changed into non-rivalrous
      stimulation, it depends on the image that has been currently dominant whether a
      change in perception occurs (incompatible change) or not (compatible change).
      That is, the perceptual experience differs although the physical input is the
      same, namely the stimulus of one eye has been changed. In the event-related brain
      potential (ERP) to compatible and incompatible changes we found differences as
      early as in the P1-N1-range, suggesting that in humans the binocular rivalry
      phenomenon is already (partly) resolved in extrastriate visual areas latest.
      Moreover, similar results were obtained with steady and flickering stimulus
      presentation showing that the processes involved in dealing with competing visual
      input do not depend critically on stimulus presentation mode.

PMID- 15500966
TI  - Drosophila nicotinic receptors: evidence for imidacloprid insecticide and alpha
      bungarotoxin binding to distinct sites.
AB  - The principal mammalian brain nicotinic acetylcholine receptors (nAChRs) are the
      alpha-bungarotoxin (alpha-BGT)-insensitive alpha 4 beta 2 and the alpha-BGT
      sensitive alpha 7 subtypes assayed with radiolabeled nicotinoids and alpha-BGT,
      respectively. Drosophila head membranes bind the insecticide radioligand
      [(3)H]imidacloprid ([(3)H]IMI) and [(3)H]alpha-BGT with K(D) 5.7 and 2.7 nM and
      B(max) 980 and 1400 fmol/mg protein, respectively. The hypothesis that [(3)H]IMI
      at 2.5 or 20 nM and [(3)H]alpha-BGT at 1 or 10 nM bind to distinct sites or
      subtypes is tested by using these radioligands alone and together in simultaneous
      dual binding experiments. These studies show no interference by one radioligand
      in the binding of the other one, i.e., independent binding, and that both
      unlabeled IMI and alpha-BGT give biphasic displacement curves. The
      pharmacological profiles of [(3)H]IMI and [(3)H]alpha-BGT suggest distinct
      binding sites for the two radioligands. These findings are consistent with those
      obtained with hybrid receptors assembled from Drosophila alpha subunits and a
      vertebrate beta subunit and with immunological and protein biochemical
      approaches. This study, therefore, provides direct evidence for distinct IMI- and
      alpha-BGT-sensitive sites or subtypes in Drosophila brain.

PMID- 15500967
TI  - Electroencephalographic peak alpha frequency correlates of cognitive traits.
AB  - EEG peak alpha frequency (PAF) has been shown to differentiate groups of adults
      with higher memory performance from those of lower performance, groups of
      children with advanced reading ability from matched controls, and to predict
      state-dependent working memory. The present study attempted to explore PAF as a
      predicting variable for verbal and attentional cognitive trait abilities in young
      adults. Nineteen undergraduate students had their EEG recorded during initial
      rest, reading, and post-reading rest, and at a different day were evaluated on
      reading, vocabulary, and attentional performance. Results showed significant
      correlations of reading vocabulary and response control with PAF during reading
      and post-reading recordings, but not during initial rest. PAF may reflect some
      general cognitive ability that is not necessarily memory or reading, possibly
      response control or the ability to acquire vocabulary. It is suggested that
      cognitive ability traits may reflect the ability to induce cognitive states.

PMID- 15500968
TI  - Hypothalamic neurons of postnatally overfed, overweight rats respond
      differentially to corticotropin-releasing hormones.
AB  - Adult overweight rats previously subjected to early postnatal overnutrition in
      small litters are hyperphagic, hyperleptinemic and differ in emotional behaviour
      from rats of control litters. We proved the hypothesis that neurons of the
      hypothalamic regulatory system of body weight differentially react to peptides of
      the corticotropin-releasing factor (CRF) family in these overweight rats. Single
      unit activity was recorded in brain slices. In controls, CRF and the CRF(2)
      receptor agonist stresscopin-related peptide (SRP) predominantly activated
      neurons of the dorsomedial part of ventromedial hypothalamic nucleus (VMHDM), but
      in overweight rats, SRP induced a significant inhibition. Increased neuronal
      firing to CRF and SRP of the medial parvocellular part of paraventricular
      hypothalamic nucleus (PaMP) in controls similarly changed to more inhibition in
      overweight rats. Inhibition of neuronal activity in VMHDM and PaMP can contribute
      to reduce satiety signals and to decrease energy expenditure in rats. In
      contrast, medial arcuate (ArcM) neurons of controls were significantly inhibited
      by SRP, whereas neurons of overweight rats could also be activated. The
      difference in the expression of these response types was significant. Activation
      of ArcM neurons known to produce neuropeptide Y can increase food intake. The
      results are discussed in terms of a trophic action of leptin changing synaptic
      wiring and the expression of excitatory and inhibitory synapses. The altered
      responses of hypothalamic neurons in adult small-litter rats may reflect a
      general mechanism of neurochemical plasticity acquired during the postnatal
      critical differentiation period, thus leading to permanently altered function of
      the regulatory system of body weight.

PMID- 15500969
TI  - Peripheral vestibular disorder induced by (+/-)-alpha-amino-3-hydroxy-5-methyl
      isoxazole-4-propionic acid (AMPA).
AB  - An intracochlear infusion of (+/-)-alpha-amino-3-hydroxy-5-methyl-isoxazole-4
      propionic acid (AMPA) was done in guinea pigs with a syringe pump and peripheral
      vestibular disorder was induced. Spontaneous nystagmus toward the intact side
      reached a peak 9 h after the infusion and disappeared within 18 h. As a control,
      artificial perilymph was infused and animals had no nystagmus. The nystagmus
      frequency was decreased by simultaneous infusion of 6-cyano-7-nitroquinoxaline
      2,3-dione (CNQX) in a dose-dependent manner. In the animals treated with AMPA or
      AMPA + CNQX, caloric tests performed 1 week after treatment revealed a partial
      dysfunction of vestibular periphery. These results indicate that the nystagmus
      observed is induced by AMPA via AMPA receptors and that AMPA-induced vestibular
      disorder is partial. This animal model may be a candidate for pharmacological
      study of inner ear diseases induced by glutamate excitotoxicity.

PMID- 15500970
TI  - Impaired SynGAP expression and long-term spatial learning and memory in
      hippocampal CA1 area from rats previously exposed to perinatal hypoxia-induced
      insults: beneficial effects of A68930.
AB  - Hypoxic encephalopathy is a common cause of neonatal seizures and long-term
      neurological cognitive deficits. In rats at postnatal days 10-12 (P10-P12),
      global hypoxia induced spontaneous seizures and chronic brain injury, mimicking
      clinical aspects of neonatal hypoxia. Synaptic Ras-GTPase activating protein
      (SynGAP) has important roles in RAS/MAPK-dependent synaptic plasticity and
      mammalian learning. We investigated possible alterations of SynGAP expression
      occurring in memory-impaired animals previously exposed to perinatal hypoxia
      insults. We also evaluated the therapeutic efficacy of A68930, a selective
      agonist of dopamine D1/D5 receptors, on perinatal hypoxia insults. In the
      hippocampal CA1 region, perinatal hypoxia insults (P10) led to a reduction in
      SynGAP expression associated with impairment in long-term spatial learning and
      memory performance at P45. The use of A68930 (at a dose of 1, 2, 3mg/kg, P17-P23)
      effectively attenuated the deleterious effects as described above. Our results
      may indicate the involvement of SynGAP in certain forms of brain injury, leading
      to long-term learning and memory deficits. A68930 may have clinical potential as
      a therapeutic agent for alleviation of long-term cognitive deficits in rats and
      other animal models.

PMID- 15500971
TI  - Brain-derived neurotrophic factor serum concentrations are increased in drug
      naive schizophrenic patients with chronic cannabis abuse and multiple substance
      abuse.
AB  - Neurotrophins such as nerve growth factor (NGF) and brain-derived neurotrophic
      factor (BDNF) are critically implicated in development and maintenance of
      function of neurons. Neurodevelopment is reported to be impaired in schizophrenia
      and vulnerable schizophrenic brains may be more sensitive to toxic influences.
      Thus, cannabis as a neurotoxin, may be more harmful to schizophrenic brains than
      to non-schizophrenic brains when used chronically. And neurotoxic events may
      promote disease-onset and lead to exaggerated release of neurotrophins. We
      investigated 157 drug-naive first-episode schizophrenic patients and found
      significantly elevated BDNF serum concentrations (by up to 34%) in patients with
      chronic cannabis abuse (n = 35, p < 0.001) or multiple substance abuse (n = 20, p
      < 0.001) prior to disease onset. Drug-naive schizophrenic patients without
      cannabis consumption showed similar results to normal controls and cannabis
      controls without schizophrenia. Thus, raised BDNF serum levels are not related to
      schizophrenia and/or substance abuse itself but may reflect a cannabis-related
      idiosyncratic damage of the schizophrenic brain. In line with this hypothesis,
      disease onset was 5.2 years earlier in the cannabis-consuming group (p = 0.0111).

PMID- 15500972
TI  - When half of the population died: the epidemic of hemorrhagic fevers of 1576 in
      Mexico.
AB  - During the 16th century, Mexico suffered a demographic catastrophe with few
      parallels in world's history. In 1519, the year of the arrival of the Spaniards,
      the population in Mexico was estimated to be between 15 and 30 million
      inhabitants. Eighty-one years later, in 1600, only two million remained.
      Epidemics (smallpox, measles, mumps), together with war, and famine have been
      considered to be the main causes of this enormous population loss. However, re
      evaluation of historical data suggests that approximately 60-70% of the death
      toll was caused by a series of epidemics of hemorrhagic fevers of unknown origin.
      In order to estimate the impact of the 1576 epidemic of hemorrhagic fevers on the
      population we analyzed the historical record and data from the 1570 and 1580
      censuses of 157 districts. The results identified several remarkable aspects of
      this epidemic: First, overall, the population loss for these 157 districts was
      51.36%. Second, there was a clear ethnic preference of the disease, the Spanish
      population was minimally affected whereas native population had high mortality
      rate. Third, the outbreak originated in the valleys of central Mexico whence it
      evolved as an expansive wave. Fourth, a positive correlation between altitude and
      mortality in central Mexico was found. Fifth, a specific climatic sequence of
      events was associated with the initiation and dissemination of the hemorrhagic
      fevers. Although the last epidemic of hemorrhagic fevers in Mexico ended in 1815,
      many questions remain to be answered. Perhaps the most relevant ones are whether
      there is a possible reemergence of the hemorrhagic fevers and how vulnerable we
      are to the disease.

PMID- 15500973
TI  - Freeze tolerance of the yeast Torulaspora delbrueckii: cellular and biochemical
      basis.
AB  - The freeze stress responses to prolonged storage at -20 degrees C in Torulaspora
      delbrueckii PYCC5323 were investigated. In this yeast, no loss of cell viability
      was observed for at least 120 days during freezing at -20 degrees C, whereas a
      loss of 80% was observed in a commercial baker's yeast after 15 days. In the
      former strain, freeze resistance was dependent on an adaptation process. The
      primary cell target of freeze stress was the plasma membrane, preservation of its
      integrity being related with a lower increase of lipid peroxidation and with a
      higher resistance to H(2)O(2), but not with the intracellular trehalose
      concentration.

PMID- 15500974
TI  - Electron microscopy analysis of Mycobacterium tuberculosis cell division.
AB  - The ultrastructure of Mycobacterium tuberculosis cells undergoing division was
      examined by electron microscopy. Two features of cell division were observed and
      are described here. First, cells are capable of undergoing a type of "snapping"
      postfission movement. This movement is likely due to a multi-layered cell wall in
      which the inner layer participates in septum formation while the outer layer
      ruptures first on one side. A second feature related to cell division is the
      ability of dividing cells to form transient branching structures.

PMID- 15500975
TI  - Identification of oligopeptide permease (opp) gene cluster in Vibrio fluvialis
      and characterization of biofilm production by oppA knockout mutation.
AB  - Oligopeptides play important roles in bacterial nutrition and signaling. The
      oligopeptide permease (opp) gene cluster was cloned from Vibrio fluvialis. The V.
      fluvialis opp operon encodes five proteins: OppA, B, C, D and F. The deduced
      amino acid sequence of these proteins showed high similarity with those from
      other Gram-negative bacteria. To investigate whether OppA is involved in biofilm
      production, an oppA knockout mutant was constructed by homologous recombination.
      The oppA mutant produced more abundant biofilm than the wild type in BHI medium.
      When both strains were grown in minimal medium, we could not detect biofilm
      formation. However, it was found that the biofilm productivity of the oppA mutant
      was two folds greater than that of the wild type in minimal medium containing
      peptone or tryptone. This variation in biofilm production was demonstrated by
      scanning electron microscopy (SEM). In minimal medium containing C-sources, both
      strains produced some biofilm without significant difference in the biofilm
      productivity. Complementation of oppA gene with the plasmid pOAC2, which contains
      oppA ORF plus promoter regions, was sufficient to restore growth rate and biofilm
      to the wild type. These results suggest that the OppA protein is involved in
      uptake of peptides and affects biofilm productivity.

PMID- 15500976
TI  - Purification of a constitutive chitosanase produced by Bacillus sp. MET 1299 with
      cloning and expression of the gene.
AB  - A chitosanase produced constitutively by Bacillus sp. MET 1299 was purified by SP
      Sephadex column chromatography. The molecular weight was estimated to be 52 kDa
      by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Optimal
      enzyme activity was observed at a pH of 5.5 and temperature of 60 degrees C. The
      purified chitosanase showed high activity on 90% deacetylated colloidal chitosan
      and beta-glucan, but not on hydrolyzed colloidal chitin, CMC, or their
      derivatives. The N-terminal amino acid sequence of the enzyme was determined. The
      cloned full length gene, 1362 bp in size, encoded a single peptide of 453 amino
      acids and had a conserved amino acid sequence of glycosyl hydrolase family 8. A
      search of the cDNA sequence with NCBI BLAST showed homology with chitosanase of
      Bacillus sp. KTCC 0377BP and Bacillus sp. No. 7-M. The recombinant protein was
      expressed in Escherichia coli, purified using affinity chromatography and
      characterized.

PMID- 15500977
TI  - Antibodies produced against a fragment of filamentous haemagglutinin (FHA) of
      Bordetella pertussis are able to inhibit hemagglutination induced by the whole
      adhesin.
AB  - Filamentous hemagglutinin adhesin (FHA) is important for the adherence of
      Bordetella pertussis to the host ciliary epithelial cells of the respiratory
      tract. Several binding domains have been characterized in the FHA molecule. For
      example, an putative heparin-binding domain of FHA was previously located in the
      FHA(442-863) region. In this work, the HEP fragment, corresponding to FHA(430
      873) was amplified by PCR and subcloned in an Escherichia coli expression
      plasmid. Purified recombinant HEP was used to produce polyclonal antibodies in
      mice that were able to recognize HEP and FHA in ELISA and in Western-blot assays.
      Although recombinant HEP displayed low ability to bind heparin and no
      hemagglutination activity, the anti-HEP antibodies were able to inhibit FHA
      mediated hemagglutination activity in goose erythrocytes. These results indicate
      that other amino acid residues that are not present in the FHA(430-873) fragment
      may be necessary for heparin binding. Further studies to address the immunogenic
      response against HEP are also required.

PMID- 15500978
TI  - Microbial degradation of the organophosphate pesticide, Ethion.
AB  - The organophosphate pesticide, Ethion, remains a major environmental contaminant
      in rural Australia and poses a significant threat to environmental and public
      health. The aerobic degradation of Ethion by mesophilic bacteria isolated from
      contaminated soils surrounding disused cattle dip sites was investigated. Two
      isolates, identified as Pseudomonas and Azospirillum species, were capable of
      biodegrading Ethion when cultivated in minimal salts medium. The abiotic
      hydrolytic degradation products of Ethion such as Ethion Dioxon and O,O
      diethylthiosphosphate were not detected. The data suggest the rapid degradation
      of Ethion to support microbial growth. The results have implications for the
      development of a bioremediation strategy.

PMID- 15500979
TI  - Regulation system for protease production in Vibrio vulnificus.
AB  - Vibrio vulnificus is a causative agent of serious food-borne diseases in humans
      related to consumption of raw seafoods. This human pathogen secretes a
      metalloprotease (VVP) that evokes enhancement of the vascular permeability and
      disruption of the capillaries. Production of microbial proteases is generally
      induced at early stationary phase of its growth. This cell density dependent
      regulation of VVP production in V. vulnificus known to be the quorum-sensing.
      When V. vulnificus was cultivated in Luria-Bertani (LB) medium, accumulation of
      the autoinducer, the signal molecule operating the quorum-sensing system, was
      detected. Moreover, expression of the vvp gene encoding VVP was found to be
      closely related with expression of the luxS gene that encode the synthase of the
      autoinducer precursor (luxS). These findings may indicate VVP production is
      controlled by the quorum-sensing system in LB medium. Furthermore, this system
      functioned more effectively at 26 degrees C than at 37 degrees C. When incubated
      at 37 degrees C in human serum supplemented with ferric chloride, production of
      VVP and expression of vvp increased in proportion to the concentration of ferric
      ion; whereas, expression of luxS was not increased. This suggests that VVP
      production in human serum containing ferric ion may be regulated mainly by the
      system other than the quorum-sensing system.

PMID- 15500981
TI  - Glycopeptide resistance determinants from the teicoplanin producer Actinoplanes
      teichomyceticus.
AB  - In enterococci and other pathogenic bacteria, high-level resistance to vancomycin
      and other glycopeptide antibiotics requires the action of the van genes, which
      direct the synthesis of peptidoglycan terminating in the depsipeptide D-alanyl-D
      lactate, in place of the usual D-Ala-D-Ala. The Actinoplanes teichomyceticus tcp
      cluster, devoted to the biosynthesis of the glycopeptide antibiotic teicoplanin,
      contains van genes associated to a murF-like sequence (murF2). We show that A.
      teichomyceticus contains also a house-keeping murF1 gene, capable of
      complementing a temperature sensitive Escherichia coli murF mutant. MurF1,
      expressed in Streptomyces lividans, can catalyze the addition of either D-Ala-D
      Ala or D-Ala-D-Lac to the UDP-N-acetyl-muramyl-L-Ala-D-Glu-d-Lys. However,
      similarly expressed MurF2 shows a small enzymatic activity only with D-Ala-D
      lactate. Introduction of a single copy of the entire set of van genes confers
      resistance to teicoplanin-type glycopeptides to S. coelicolor.

PMID- 15500980
TI  - Community structure in a methanotroph biofilter as revealed by phospholipid fatty
      acid analysis.
AB  - The microbial community structure of two biofilters used for the oxidation of
      methane and organic trace gases generated in landfills was analysed by
      phospholipid fatty acid composition. Community structure varied with biofilter
      depth, reflecting varying conditions of substrate supply as well as of organic
      carbon content, nutrient status and osmotic stress determined by the different
      materials used for the individual biofilter layers. Both biofilters were
      dominated by type II methanotrophs. In the biofilter charged with landfill gas
      containing significant amounts of trace organics, fatty acid 18:1omega7c
      constituted 87% of the methanotrophic PLFA, while the recognised signature fatty
      acids 16:1omega8 and 18:1omega8, which were well represented in the other
      biofilter, were entirely absent. This indicates the development of a highly
      specific methanotrophic population, presumably as a result of the adaption to
      continuous organic trace gas exposure.

PMID- 15500982
TI  - RegM is required for optimal fructosyltransferase and glucosyltransferase gene
      expression in Streptococcus mutans.
AB  - Glucosyltransferases (Gtfs) and fructosyltransferase (Ftf), and the
      exopolysaccharides they produce, facilitate bacterial adherence and biofilm
      formation, and enhance the virulence of Streptococcus mutans. In this study, we
      used continuous chemostat cultures and reporter gene fusions to study the
      expression of ftf and gtfBC in response to carbohydrate availability and pH, and
      to asses the role of a protein similar to catabolite control protein A (CcpA),
      RegM, in regulation of these genes. Expression of ftf was efficient at pH 7.0 and
      6.0, but was repressed at pH 5.0 under glucose-excess conditions. At pH 7.0, ftf
      expression was 5-fold lower under glucose-limiting conditions than in cells
      growing with an excess of glucose. Expression of gtfBC was also sensitive, albeit
      to a lesser extent, to pH and glucose availability. Inactivation of regM resulted
      in decreases of as much as 10-fold in both ftf and gtfBC expression, depending on
      growth conditions. These findings reinforce the importance of pH and carbohydrate
      availability for expression of two primary virulence attributes of S. mutans and
      reveal a critical role for RegM in regulation of expression of both gtfBC and
      ftf.

PMID- 15500983
TI  - Single channel evidence for innate pore-formation by Vibrio parahaemolyticus
      thermostable direct haemolysin (TDH) in phospholipid bilayers.
AB  - Vibrio parahaemolyticus thermostable direct haemolysin (TDH) is widely considered
      to be a pore-forming toxin. The protein has no significant homology to other
      known pore-forming toxins and its mechanism of action in vivo remains undefined.
      We demonstrate single channel pore-forming activity of V. parahaemolyticus TDH in
      planar lipid bilayers. Channel conductance ranged between 30-450 pS in 0.5 M KCl
      with a calculated cation selectivity (P(K)/P(Cl)) of 2.7. Channels were formed in
      NaCl and choline-Cl with and without cholesterol present and in the presence of
      neutral or negatively charged phospholipids. Zinc ions did not block pore
      formation. Whilst various techniques have previously suggested that TDH is a pore
      forming toxin, the data in this study provide direct single channel evidence and
      indicate several features of pore formation in synthetic phospholipid membranes.

PMID- 15500984
TI  - Evaluation of randomly amplified polymorphic DNA and pulsed field gel
      electrophoresis techniques for molecular typing of Dermatophilus congolensis.
AB  - This study aimed to evaluate molecular typing methods useful for standardization
      of strains in experimental work on dermatophilosis. Fifty Dermatophilus
      congolensis isolates, collected from sheep, cattle, horse and a deer, were
      analyzed by randomly amplified polymorphic DNA (RAPD) method using twenty-one
      different primers, and the results were compared with those obtained by typing
      with a pulsed field gel electrophoresis (PFGE) method using the restriction
      digest enzyme Sse8387I. The typeability, reproducibility and discriminatory power
      of RAPD and Sse8387I-PFGE typing were calculated. Both typing methods were highly
      reproducible. Of the two techniques, Sse8387I-PFGE was the least discriminating
      (Dice Index (DI), 0.663) and could not distinguish between epidemiologically
      related isolates, whereas RAPD showed an excellent discriminatory power (DI,
      0.7694-0.9722). Overall, the degree of correlation between RAPD and PFGE typing
      was significantly high (r, 0.8822). We conclude that the DNA profiles generated
      by either RAPD or PFGE can be used to differentiate epidemiologically unrelated
      isolates. The results of this study strongly suggest that at least two
      independent primers are used for RAPD typing in order to improve its
      discriminatory power, and that PFGE is used for confirmation of RAPD results.

PMID- 15500985
TI  - Enzymatic reactions in anaerobic 2-methylnaphthalene degradation by the sulphate
      reducing enrichment culture N 47.
AB  - The upper pathway of anaerobic degradation of 2-methylnaphthalene was studied
      with a sulphate-reducing enrichment culture, which is able to grow with
      naphthalene or 2-methylnaphthalene as sole carbon source and electron donor.
      Anaerobic degradation of 2-methylnaphthalene is initiated by an addition of
      fumarate to the methyl-group producing the first intermediate, naphthyl-2-methyl
      succinate. In a subsequent beta-oxidation of the original methyl atom, the
      central metabolite 2-naphthoic acid is generated. In the following pathway, the
      aromatic ring system is reduced, cleaved, and finally oxidised to CO(2). Here, we
      present two new enzymatic reactions of the 2-methylnaphthalene degradation
      pathway that were measured in crude cell extracts. All metabolites were
      identified with HPLC by co-elution with synthesised reference substances. The
      first enzyme, succinyl-CoA:naphthyl-2-methyl-succinate CoA-transferase, catalyses
      the activation of naphthyl-2-methyl-succinic acid to the corresponding CoA ester.
      The average specific activity of this enzyme was 19.6 nmol x min(-1) x mg of
      protein(-1). The CoA-transfer was not inhibited by sodium borohydride and only
      partially by hydroxylamine, indicating that this enzyme belongs to the family III
      of CoA-transferases like the corresponding enzyme in the anaerobic toluene
      degradation pathway. The product of this CoA-transfer reaction, naphthyl-2-methyl
      succinyl-CoA is then oxidised in a reaction to naphthyl-2-methylene-succinyl-CoA
      by the enzyme naphthyl-2-methyl-succinyl-CoA dehydrogenase. The specific activity
      of this enzyme was 0.115 nmol x min(-1) x mg of protein(-1). The enzymatic
      activity could only be detected using phenazine methosulphate as electron
      acceptor. No activity was observed with natural electron acceptors such as
      nicotinamide adenine dinucleotide or flavin adenine dinucleotide. The two novel
      reactions presented here demonstrate that the original methyl-group of 2
      methylnaphthalene is oxidised to the carboxyl group of 2-naphthoic acid in the
      upper part of the anaerobic degradation pathway.

PMID- 15500986
TI  - Investigation of morphological changes to Staphylococcus aureus induced by ovine
      derived antimicrobial peptides using TEM and AFM.
AB  - The effect of two ovine-derived peptides on the morphology of Staphylococcus
      aureus NCTC 4163 cells were investigated using transmission electron microscopy
      and atomic force microscopy. Both techniques showed that SMAP29, an alpha-helical
      peptide, induced cell lysis, whereas OaBac5mini, a proline/arginine-rich peptide,
      caused no observable morphological changes. This is consistent with previous
      experimental work which indicated that SMAP29 caused cell death and induced cell
      lysis, whereas OaBac5mini acted by interacting with the inner cellular contents.

PMID- 15500987
TI  - Galangin expresses bactericidal activity against multiple-resistant bacteria:
      MRSA, Enterococcus spp. and Pseudomonas aeruginosa.
AB  - The antimicrobial activity of three propolis ethanol extracts (EEP) was examined
      for various Gram-negative and Gram-positive bacterial species, including multiple
      resistant Staphylococcus aureus, Enterococcus spp. and Pseudomonas aeruginosa
      strains. EEP had a good bactericidal activity against Gram-positive species, and
      all multiple-resistant bacterial strains tested were sensitive to EEP. Minimal
      inhibitory concentrations (MICs) were lower in samples of higher flavonoid
      content (from 0.65 to 7.81 mg mL(-1)), indicating the influence of the
      concentration of some potent bactericidal compound(s) in propolis or synergism
      among some bactericidal compounds. Antimicrobial-guided separation of flavonoid
      aglycones (bioassay in situ on thin-layer chromatogram) showed that galangin
      (3,5,7-trihydroxyflavone) is one compound in EEP with bactericidal activity.
      Galangin was isolated by preparative chromatography. After determining the
      quantity present, the MIC against multiple-resistant bacteria was determined. The
      MIC of galangin against multiple-resistant bacterial strains was significantly
      lower (from 0.16 to 0.44 mg mL(-1), p < 0.05) than that of EEP. The bactericidal
      activity of galangin against P. aeruginosa strains was present at 0.17+/-0.05 mg
      mL(-1).

PMID- 15500988
TI  - An endo-polygalacturonase (PG) of Fusarium moniliforme escaping inhibition by
      plant polygalacturonase-inhibiting proteins (PGIPs) provides new insights into
      the PG-PGIP interaction.
AB  - Polygalacturonase-inhibiting proteins (PGIPs) are plant defence molecules
      inhibiting the activity of fungal endo-polygalacturonases (endo-PGs). We found
      that soybean and bean PGIPs inhibited the endo-PG activity produced by the
      isolate FC-10 of Fusarium moniliforme but not the enzyme activity produced by the
      isolate PD of F. moniliforme. The bean PGIP proved to be ineffective against all
      the PG isoforms produced by the PD isolate. Deduced amino acid sequence
      comparison between PGs from PD, FC-10 and 62264 isolates identified the
      structural regions of the enzyme possibly related to its resistance to PGIP
      inhibition. These include one region at the N-terminal portion of the enzyme and
      a few single amino acid substitutions along the entire sequence, two of which
      surrounding the active site.

PMID- 15500989
TI  - Idiopathic infantile asymmetry, proposal of a measurement scale.
AB  - To evaluate the development of idiopathic infantile asymmetry and the efficacy of
      therapeutic interventions, spinal scoliosis can be quantified on the basis of
      radiographs. For obvious reasons, use of this technique is limited. Here we
      present a clinical method to describe and quantify infantile asymmetry. For item
      selection, spontaneous movements (SMs), reactive movements (RMs) and length
      differences were video recorded in 30 infants (median age 10 weeks, range 6-16)
      with variable degrees of asymmetry. Within these three categories, reactive
      movements elicited by head turns to the right and left side in the prone and
      supine position emerged as reliable parameters reflecting trunk convexity and
      cervical rotation deficits. Six-point scales were developed for both measurements
      and added to form final scales. Consistency and interobserver reliability were
      evaluated in another 20 infants (median age 9 weeks, range 6-15) with variable
      degrees of asymmetry. Statistical analysis indicated good reliability and
      consistency of the testing method with an intraclass correlation coefficient of
      91.5% (Cronbach alpha 0.84). CONCLUSION: During the first months of life,
      idiopathic infantile asymmetry can be clinically assessed using a highly
      consistent and reliable measurement scale describing degrees of trunk convexity
      and cervical rotations deficit.

PMID- 15500990
TI  - Obstetric optimality and emotional problems and substance use in young adulthood.
AB  - BACKGROUND: Pregnancy and delivery are complex processes, and isolated obstetric
      complications rare and often accompanied or followed by a number of others. AIMS:
      To study the relationship between the overall obstetric situation (as opposed to
      single obstetric risk factors) and emotional and substance use disorders in young
      adulthood, and to analyse whether these links are mediated by temperaments in
      childhood. STUDY DESIGN: In a prospective birth cohort (n=3162), questionnaires
      were sent to mothers and teachers when the child was 7-10 years old, and to the
      children when they were 20-25 years old. SUBJECTS: Six hundred and eighty-two
      cohort members with complete data sets at three ages (perinatal, childhood, and
      young adulthood). OUTCOME MEASURES: Emotional problems and substance use in young
      adulthood. MAIN RESULTS: Substance use in young adulthood was predicted better by
      the overall obstetrical optimality score than emotional problems were. Links
      studied were stronger for men than for women. CONCLUSIONS: This study
      demonstrated the use of an aggregated obstetrical optimality score in analysing
      the associations between early risk factors and emotional problems and substance
      use in young adulthood.

PMID- 15500991
TI  - Neonatal intensive care at borderline viability--is it worth it?
AB  - BACKGROUND: Very preterm infants at the borderline of viability, especially those
      <25 weeks of gestational age, have survived in increasing numbers in recent
      years, but concerns persist about their long-term outcome and their consumption
      of scarce hospital resources. AIMS: To determine incremental changes in long-term
      outcome and consumption of resources by very preterm infants in the 1990s.
      DESIGN: Cohort study. PATIENTS: Consecutive livebirths with gestational ages 23
      27 weeks born in the state of Victoria in two discrete eras, 1991-1992 (n=401)
      and 1997 (n=208), and randomly selected contemporaneous normal birthweight (NBW,
      birthweight >2499 g) controls (1991-1992 n=265, 1997 n=198). MAIN OUTCOME
      MEASURES: Survival, and neurosensory impairments, disabilities and utilities, and
      consumption of hospital resources to 2 years of age. RESULTS: Compared with 1991
      1992, in 1997 more infants were offered intensive care and the survival rate was
      higher at each week of gestation, and overall (absolute increase in survival 16%;
      95% confidence interval, 8%, 24%). The largest increases in the survival and
      quality-adjusted survival rates were in infants at 23 weeks (31% and 20%,
      respectively). The incremental resource costs of improving survival and quality
      adjusted survival were similar in infants of 23-24 weeks compared with those of
      25-27 weeks (e.g., 112 vs. 105 days of assisted ventilation per additional
      survivor, or 167 vs. 180 days of assisted ventilation per additional quality
      adjusted survivor, respectively). CONCLUSIONS: Increased intensive care in the
      late 1990s for infants at the borderline of viability was associated with
      improved outcomes, at incremental costs that were not excessive compared with
      slightly more mature infants.

PMID- 15500992
TI  - First two months of pregnancy--critical time for preterm delivery and low
      birthweight caused by adverse effects of coal combustion toxics.
AB  - OBJECTIVE: The objective of this study was to define the most critical gestation
      period for adverse effects of environmental toxics in terms of preterm delivery
      (<37 weeks) and low birthweight (<2500 g) in humans. STUDY DESIGN: From January
      1, 1987 to December 31, 1989, 704 women were included in a retrospective
      epidemiological study. All were from the district of Labin and lived in the
      vicinity of a coal power plant Plomin 1, Croatia. This plant is the single large
      source of air pollution in the area. The coal used for fuel is extremely rich
      with sulfur, 9-11%. Daily, weekly, and monthly consumption of coal and related
      SO2 emissions were calculated for each pregnant woman from the beginning to the
      end of pregnancy. RESULTS: We found that a greater and longer exposure to SO2
      emissions during the initial two months of pregnancy resulted in a significantly
      shorter gestation (end of the first month: -0.0914, p=0.008, end of the second
      month: -0.0806, p=0.016) and in lower body mass of a newborn (end of the first
      month: -0.0807, p=0.016, end of the second month -0.0733, p=0.026). CONCLUSION:
      The results of this study confirm the role of inhaled environmental toxics in the
      early development of human embryo and in adverse pregnancy course caused by
      permanent oxidative stress, misbalanced production of reactive oxygen species
      (ROS), reactive nitrogen species (RNS), reactive sulfur species (RSS), and other
      unfavorable metabolic processes on early embryogenesis, resulting in growth
      arrested cells.

PMID- 15500993
TI  - Hypoxic-ischemic brain injury in the term infant-current concepts.
AB  - An enhanced understanding of the cellular characteristics contributing to ongoing
      brain injury following intrapartum hypoxia-ischemia has resulted in the
      implementation of targeted neuroprotective strategies in the newborn period. This
      review briefly covers the pathogenesis of hypoxic-ischemic injury with an
      emphasis on reperfusion injury; the role of magnetic resonance imaging in the
      detection of such injury, and focuses on potential strategies both supportive and
      neuroprotective to prevent ongoing injury with a specific emphasis on modest
      hypothermia.

PMID- 15500994
TI  - Use of folic acid supplementation and risk for dizygotic twinning.
AB  - BACKGROUND: An increase in dizygotic twinning rate after folic acid
      supplementation has previously been described, but in a recent study from China,
      no such effect was seen. AIMS: To further investigate the association between use
      of folic acid supplement and dizygotic twinning. STUDY DESIGN: Using the Swedish
      Medical Birth Registry, the rate of dizygotic twinning among infants of women who
      reported the use of folic acid was studied, taking a number of confounders into
      consideration. Comparisons were made with all women recorded in the register.
      OUTCOME MEASURE: Unlike-sexed twin pairs were used as representatives of
      dizygotic twinning. RESULTS: A number of confounders for the association between
      folic acid use and twinning were identified and taken into consideration. Women
      who were immigrants (who used less folic acid and had slightly lower twinning
      rates than women born in Sweden) and women who reported subfertility problems or
      treatment for subfertility (who had a high use of folic acid and a high twinning
      rate) were excluded, and adjustment was then made for year of birth, maternal
      age, parity, and smoking in early pregnancy. Folic acid use and twinning risk
      increased with maternal age and decreased with parity. Smokers used less folic
      acid than nonsmokers. Concomitant use of other drugs was no important confounder
      except for those used at subfertility. The odds ratio (OR) for dizygotic twinning
      after folic acid supplementation was then 1.71 (95%CI=1.21-2.42) and for the
      years 2000-2001 even 2.09 (95%CI=1.39-3.12). CONCLUSION: There is an increase in
      twinning rate after folic acid supplementation in a Western population which
      should be taken into consideration when folic acid supplementation or food
      fortification is recommended.

PMID- 15500995
TI  - Parental race, birth weight, gestational age, and fetal growth among twin infants
      in the United States.
AB  - BACKGROUND: No previous study has examined the association between paternal race
      and birth weight among twins. AIMS: To examine the association of parents' race
      and birth weight among twins. STUDY DESIGN: Population-based retrospective cohort
      study to examine the association between parents' race and birth weight, and its
      two components, gestation duration and fetal growth among four group of infants:
      both parents blacks (FB-MB), father white and mother black (FW-MB), father black
      and mother white (FB-MW), and both parents whites (FW-MW), with "risk-free"
      analysis to control confounding factors. SUBJECTS: Twin births (304,466 twins)
      registered in the United States in 1995-1997. OUTCOME MEASURES: The means of
      birth weight, gestational age, and birth-weight-for-gestational age z score, and
      rates of very low birth weight (VLBW, <1500 g), very preterm birth (VPTB, <32
      weeks of gestation), and fetal growth restriction (FGR, <10th percentile of z
      score). RESULTS: Means of birth weight, gestational age, and z score were 2234.0,
      2301.9, 2361.1, and 2433.8, and 35.02, 35.24, 35.65, and 35.78, and -0.136, 
      0.070, -0.039, and 0.063, respectively, and the rates of VLBW, VPTB, and FGR were
      14.5, 12.3, 10.5, and 8.1, and 16.0, 13.0, 11.6, and 9.2, and 12.6, 11.1, 10.8,
      and 8.7, respectively, in the FB-MB, FW-MB, FB-MW, and FW-MW groups. Excluding
      subjects with various risk factors by risk-free analysis did not change the
      results. CONCLUSIONS: Both parents' races are important determinants of birth
      weight, gestational age, and fetal growth among twin pregnancies, with higher
      effect on gestational age and greater maternal influence than paternal influence.

PMID- 15500996
TI  - Sex and ethnic differences in 2nd to 4th digit ratio of children.
AB  - BACKGROUND: The ratio between the length of the 2nd or index finger and the 4th
      or ring finger (2D:4D) differs between the sexes, such that males have lower
      2D:4D than females, and shows considerable ethnic differences, with low values
      found in Black populations. It has been suggested that the sex difference in
      2D:4D arises early in development and that finger ratio is a correlate of
      prenatal testosterone and oestrogen. In children, 2D:4D has been reported to be
      associated with measures of fetal growth, congenital adrenal hyperplasia,
      developmental psychopathology, autism and Asperger's syndrome. However, little is
      known of the patterns of sex and ethnic differences in the 2D:4D ratio of
      children. AIM: To investigate sex and ethnic differences in 2D:4D in Caucasian,
      Oriental and Black children. STUDY DESIGN: Population survey. METHOD: The 2D:4D
      ratio was measured from photocopies of the right hand of Berber children from
      Morocco, Uygur and Han children from the North-West province of China, and
      children from Jamaica. RESULTS: There were 798 children in the total sample (90
      Berbers, 438 Uygurs, 118 Han, and 152 Jamaicans). The 2D:4D ratio was lower in
      males than in females and this was significant for the overall sample and for the
      Uygur, Han and Jamaican samples. There were significant ethnic differences in
      2D:4D. The Oriental Han had the highest mean 2D:4D, followed by the Caucasian
      Berbers and Uygurs, with the lowest mean ratios found in the Afro-Caribbean
      Jamaicans. The sex and ethnic differences were independent of one another with no
      significant interaction effect. In the overall sample there were no associations
      between 2D:4D and age and height. CONCLUSIONS: In common with adults, the 2D:4D
      ratio of children shows sex and ethnic differences with low values found in a
      Black group. There was no overall association between 2D:4D and age and height
      suggesting that the sex and ethnic differences in 2D:4D appear early and do not
      show appreciable change with growth.

PMID- 15500997
TI  - Evaluation of photostability of solid-state nicardipine hydrochloride polymorphs
      by using Fourier-transformed reflection-absorption infrared spectroscopy - effect
      of grinding on the photostability of crystal form.
AB  - Photostability and physicochemical properties of nicardipine hydrochloride
      polymorphs (alpha- and beta-form) were studied by using Fourier-transformed
      reflection-absorption infrared spectroscopy (FT-IR-RAS) of the tablets, X-ray
      powder diffraction analysis, differential scanning calorimetry (DSC), and color
      difference measurement. It was clear from the results of FT-IR-RAS spectra after
      irradiation that nicardipine hydrochloride in the solid state decomposed to its
      pyridine derivative when exposed to light. The photostability of the ground
      samples of two forms was also measured in the same manner. The two crystalline
      forms of the drug changed to nearly amorphous form after 150 min grinding in a
      mixer mill. X-ray powder diffraction patterns of those ground samples showed
      almost halo patterns. The nicardipine hydrochloride content on the surface of the
      tablet was determined based on the absorbance at 1700 cm(-1) attributable to the
      C=O stretch vibration in FT-IR-RAS spectra before and after irradiation by
      fluorescent lamp (3500 lx). The photodegradation followed apparently the first
      order kinetics for any sample. The apparent photodegradation rate constant of
      beta-form was greater than that of alpha-form. The ground samples decomposed
      rapidly under the same light irradiation as compared with the intact crystalline
      forms. The photodegradation rate constant decreased with increase of the heat of
      fusion.

PMID- 15500998
TI  - Intracellular disposition of polysaccharides in rat liver parenchymal and
      nonparenchymal cells.
AB  - Binding and internalization of arabinogalactan, pullulan, dextran, and mannan
      were examined in rat liver parenchymal and nonparenchymal cells using 125I or
      fluorescein isothiocyanate (FITC) labeled polysaccharides. Binding and uptake of
      arabinogalactan and pullulan into parenchymal cells was inhibited by
      asialofetuin, indicating that the asialoglycoprotein receptor is involved in the
      intracellular disposition of arabinogalactan and pullulan. Uptake of 125I-labeled
      dextran to parenchymal cells was unchanged upon addition of excess unlabeled
      dextran, suggesting that dextran uptake occurs via fluid phase endocytosis. Of
      the polysaccharides tested, mannan showed the strongest specific association with
      liver nonparenchymal cells. FITC-labeled polysaccharides showed arabinogalactan
      and pullulan are internalized to liver parenchymal cells, whereas mannan is
      internalized to nonparenchymal cells. This study demonstrates that intracellular
      disposition of polysaccharides in the liver occurs via receptor-mediated
      endocytosis (RME), indicating that RME plays a role in the biodisposition of
      these polysaccharides as drug carriers.

PMID- 15500999
TI  - Partial solubility parameters of poly(D,L-lactide-co-glycolide).
AB  - During production of microparticles by the polymer incompatibility method a
      polymer solution is demixed. Therefore, investigations into solubility are often
      carried out when the suitability of a polymer is examined. Solubility parameters
      can be used to quantify the solubility. For polylactide and polyglycolide as
      commonly employed copolymers for microparticles the solubility parameters have
      rarely been documented. This study aimed to determine solubility parameters and
      partial solubility parameters for different proportions of lactide to glycolide
      for poly(D,L-lactide-co-glycolide) (PLGA). The employed methods were compared and
      solubility maps established. Finally the accuracy of the results was discussed
      for different polymer batches which were used for production of microparticles.
      Although the turbidity titration method was found to be the most precise, it was
      not possible to sufficiently explain the differences between three polymer
      batches during microparticle production.

PMID- 15501001
TI  - Membrane permeability and antipyrine absorption in a rat model of ischemic
      colitis.
AB  - The aim of this study was to determine whether the duration of ischemia affects
      antipyrine absorption in the large intestine. This was carried out in a rat model
      of ischemic colitis in which ischemia and associated inflammation was induced by
      marginal vessel ligation. Blood flow was disrupted by positioning an o-ring
      around the distal rectum and ligating the marginal vessel at two locations in the
      hind-gut ligament artery region. Ligation was performed for 1, 2, 3, and 5h. We
      assessed large intestine damage by measuring key indicators of inflammation,
      myeloperoxidase (MPO) activity and thiobarbituric acid reactant substrates
      (TBARS) in the mucosa and by histological staining with hematoxylin-eosin stain.
      Antipyrine membrane permeability was assessed in Ussing-type diffusion chambers,
      and related pharmacokinetics were calculated from antipyrine plasma concentration
      measurements following colon administration of the drug. Vessel ligation caused
      some sloughing of epithelial cells and elevated the MPO and TBARS levels.
      Prolonged ligation failed to affect the apparent permeability coefficient
      (P(app)) of antipyrine. Prolonged ligation, however, gradually increased plasma
      antipyrine concentrations to near control levels. This increase was paralleled by
      increases in the absorption rate constant AUC and antipyrine bioavailability.
      Taken together, these results suggest that the absorption kinetics of antipyrine
      may depend on blood flow changes in the large intestine that occur with
      inflammation.

PMID- 15501000
TI  - Formulation and evaluation of diclofenac sodium buccoadhesive discs.
AB  - Twenty diclofenac sodium buccoadhesive discs containing Cp974p, polycarbophil,
      PEO, SCMC-medium viscosity (SCMC-MV), SCMC-ultrahigh viscosity (SCMC-UHV) or
      their combinations were prepared. These buccoadhesive discs were evaluated for
      release pattern, swelling capacity, surface pH, mucoadhesion performance, and in
      vitro permeation of diclofenac sodium through buccal membranes. In vivo testing
      of mucoadhesion time, strength of adhesion, irritation, bitterness due to drug
      swallowing and disc disintegration in the buccal cavity were also performed. Drug
      bioavailability of a selected diclofenac sodium buccoadhesive product was then
      compared with that of Voltarin 100 SR tablet. The percentage relative
      bioavailability of diclofenac sodium from the selected buccoadhesive disc 50 mg
      was found to be 141.31%.

PMID- 15501002
TI  - The improved dissolution and prevention of ampoule breakage attained by the
      introduction of pretreatment into the production process of the lyophilized
      formulation of recombinant human Interleukin-11 (rhIL-11).
AB  - Lyophilized protein formulations sometimes pose problems such as the formation of
      a cloudy solution upon reconstitution. Ampoule or vial breakage can also occur
      during the production processes of lyophilized pharmaceutical products. Various
      efforts have been made to overcome those difficult problems. In this study, we
      introduce a particular temperature program into the production process of a
      recombinant human Interleukin-11 (rhIL-11) lyophilized formulation containing
      sodium phosphates (Na2HPO4/NaH2PO4, pH 7.0) and glycine in an attempt to improve
      its dissolution properties and to prevent ampoule breakage from occurring. The
      formulation was pretreated by nucleating ice and maintaining the solution
      overnight at a temperature of -6 degrees C. The solution was then completely
      frozen at a lower temperature. This pretreatment proved successful in not only
      producing a lyophilized cake which readily disintegrated and dissolved in the
      reconstitution media, but also prevented ampoule breakage from occurring during
      the production processes. In contrast, a lyophilized cake produced without the
      pretreatment created a cloudy solution particularly when reconstituted using
      water for injection contaminated with aluminum (Al3+), although the solution
      became transparent within 20-30 min. The pretreatment induced the crystallization
      of sodium dibasic phosphate (Na2HPO4) in the freeze-concentrate whereas direct
      freezing without the pretreatment did not crystallize the salt. Thermal analyses
      (DSC and TMA) showed that amorphous sodium dibasic phosphate in the freeze
      concentrate became crystallized upon heating, accompanied by an increase in
      volume, which probably caused the ampoule breakage that occurred without the
      pretreatment. Although power X-ray diffraction (PXRD) experiments suggested that,
      with or without the pretreatment, glycine assumed the beta-form and sodium
      phosphate stayed amorphous in the final products, an electrostatic interaction
      between dibasic phosphate anions and rhIL-11, a highly cationic protein, would
      only exist in the lyophilized cake produced without the pretreatment. This
      interaction is highly likely because aluminum facilitates the formation of a
      cloudy solution upon reconstitution possibly by using the divalent anions which
      effectively reduce electrostatic repulsions between aluminum and the protein to
      form an aggregate structure that is not readily soluble. The pretreatment would
      circumvent the interaction by crystallizing the sodium salt before freezing
      creating a relatively soluble lyophilized cake that is much less sensitive to
      aluminum.

PMID- 15501003
TI  - Enhancing the bioavailability of ABT-963 using solid dispersion containing
      Pluronic F-68.
AB  - Solid dispersions using Pluronic F-68 as a carrier were studied for improving the
      dissolution and bioavailability of ABT-963, a poorly water-soluble compound. The
      solid dispersions were prepared either by evaporation of the ethanol solutions
      containing ABT-963 and Pluronic, or by cooling the hot melt of the drug in the
      carrier. The dispersions were characterized using differential scanning
      calorimetry, powder X-ray diffractometry, scanning electron microscopy, elemental
      mapping, and by constructing the melting point phase diagram. In vitro
      dissolution and in vivo oral bioavailability in fasted dogs were compared for the
      solid dispersion and a conventional IR capsule formulation. Results showed that,
      at a composition of approximately 7.5%, ABT-963 formed a eutectic mixture with
      Pluronic F-68. Both the drug and the polymer were crystalline in the solid
      dispersion with a wide range of composition of each component. The solid
      dispersion substantially increased the in vitro dissolution rate of ABT-963.
      Dosing of the dispersion to fasted dogs resulted in a significant increase of
      oral bioavailability compared with the conventional IR capsule formulation. These
      results show that solid dispersion is a promising approach for developing ABT-963
      drug products.

PMID- 15501004
TI  - Applicability of (SBE)7m-beta-CD in controlled-porosity osmotic pump tablets
      (OPTs).
AB  - The purpose of this study was to investigate the general application of a
      controlled-porosity osmotic pump tablet (OPT) utilizing (SBE)7m-beta-CD as both a
      solubilizer and an osmotic agent for drugs with varying physical properties. OPTs
      utilizing (SBE)7m-beta-CD were prepared for five poorly soluble and two highly
      water-soluble drugs. The Japanese Pharmacopoeia dissolution method was used to
      study the drug and (SBE)7m-beta-CD release from the OPTs. The drug concentration
      in the OPT core after the OPT was placed in the release medium for two hours was
      assayed gravimetrically and by HPLC. An appropriate composition ratio (ACR) of
      (SBE)7m-beta-CD to drug at which drug release from the OPT was complete and pH
      independent within the physiological pH range of the GI tract was determined for
      each drug. The ACR values correlate to the drug concentration in the OPT core
      when the OPTs were placed in the release medium for two hours. The release
      profiles of prednisolone (a poorly water-soluble drug) and sodium chloride (a
      water-soluble compound) from the OPTs were almost the same as that of (SBE)7m
      beta-CD. Also, the release rate of each drug per unit membrane surface area from
      the OPTs was similar, regardless of the differences in drug solubility. The
      present results confirmed that (SBE)7m-beta-CD serves as both a solubility
      modulator and as an osmotic pumping agent for OPTs, from which the release rate
      of both water-soluble and poorly water-soluble drugs can be controlled.

PMID- 15501005
TI  - Characterization of the influence of nitric oxide donors on intestinal absorption
      of macromolecules.
AB  - To characterize the influence of nitric oxide (NO) donors on the intestinal
      absorption of macromolecules, the relationship between the release rate of NO
      from NO donors and their absorption-enhancing effects and the effects of several
      scavengers and generators on the absorption-enhancing effects of NO donor were
      investigated. The t1/2 values of the NO release rate from 3-(2-hydroxy-1
      methylethyl-2-nitrosohydrazino)-1-propanamine (NOC5), 3-(2-hydroxy-1-methylethyl
      2-nitrosohydrazino)-N-methyl-1-propanamine (NOC7) and N-ethyl-2-(1-ethyl-hydroxy
      2-nitrosohydrazino)-ethanamine (NOC12) are 25, 5 and 100min, respectively. The
      absorption-enhancing effects of NO donors on the absorption of fluorescein
      isothiocyanate dextrans with an average molecular weight of 4400 (FD-4) are NOC5
      > NOC7 > NOC12 in the colon. The lowest enhancing effect of NOC12 may be due to
      the slow rate of NO release. The enhancing effect of NOC7 rapidly disappeared
      compared with the effect of NOC5. The results raise the possibility that the
      difference between NOC5 and NOC7 on enhancing effect is related to the t1/2 of
      the NO release. The NOC7-induced enhancing effect was prevented by the co
      administration of 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazole-1-oxyl-3-oxide
      sodium salt (C-PTIO), an NO scavenger; tiron, an O2(-) scavenger; mannitol, an
      OH* scavenger, and deferoxamine, peroxynitrate scavenger. Pyrogallol, an O2(-)
      generator, potentiated the NOC7-induced enhancing effect. These results support a
      role for peroxynitrate, and possibly OH*, in the NO donor-induced intestinal
      enhancing effect.

PMID- 15501006
TI  - A novel pH-dependent gradient-release delivery system for nitrendipine II.
      Investigations of the factors affecting the release behaviors of the system.
AB  - Nitrendipine, a dihydropyridine calcium antagonist, was used as a poorly water
      soluble model drug. To improve its dissolution rate and extend the therapeutic
      period in vivo as well, a novel pH-dependent gradient-release drug delivery
      system for nitrendipine having a solid dispersed matrix structure was developed.
      Four factors, i.e. the amount of excipients, the pH of the dissolution medium,
      the rotating speed of the paddle of the dissolution apparatus and the particle
      size of the microspheres, all of which affect the drug-release behavior of the pH
      dependent microspheres of the system were investigated in detail. The release
      profiles of the pH-dependent drug delivery system under simulated
      gastrointestinal tract pH conditions were also investigated. The results showed
      that the release rate of drug from the microspheres increased on increasing the
      amount of respective pH-dependent polymers formulated. Due to the fact that the
      active drug was incorporated in pH-dependent polymers and was present in a solid
      dispersion state in the microspheres, the release rate of the drug from the
      microspheres depended on the dissolution rate of the polymers, which was mainly
      influenced by the pH of dissolution medium, whereas the rotating speed of the
      paddle and the particle size of the microspheres had only a relatively minor
      effect. The release behavior of the system under simulated gastrointestinal tract
      conditions exhibited obvious gradient-release characteristics, showing that the
      release rate of the active drug could be controlled efficiently before the
      microspheres reached the appropriate region of the gut for absorption. These
      findings suggest that the pH-dependent drug delivery system could be fabricated
      by using present microspheres.

PMID- 15501007
TI  - Estimation of the ethanol/water solubility profile from the octanol/water
      partition coefficient.
AB  - While the ethanol/water solubility profiles of very polar and very non-polar
      drugs are monotonic, many semi-polar drugs show a maximum solubility at an
      ethanol volume fraction (f(max)) between 0 and 1. A sigmoidal relationship was
      observed between the value of f(max) and the log of the octanol/water partition
      coefficient (logK(ow)) of the solute. This relationship reasonably predicts the
      value of the volume fraction of ethanol that gives maximum solubility (f(max)).
      Combining this sigmoidal relationship with the previously reported linear
      relationship between the logK(ow) and the initial slope of the plot of log
      solubility versus ethanol composition [Li, A., Yalkowsky, S.H., 1994. Solubility
      of organic solutes in ethanol/water mixtures. J. Pharm. Sci. 83, 1735-1740]
      enables the estimation of the total ethanol/water solubility profile.

PMID- 15501009
TI  - Predicting polymorphic transformation curves using a logistic equation.
AB  - The commonly used solid-state reaction models (for example-Prout-Tompkins, Avrami
      Erofe'ev) describe the polymorphic transformation data only over a certain range,
      alpha from 10% to 90%. Predictions based on a fit to a fraction of the data are
      inadequate because we ignore the early induction phase of the reaction, which is
      important for predictive purposes. A four-parameter logistic equation describes
      the data over the entire curve for polymorphic transformation at high
      temperatures. We use the parameters of the logistic equation to predict the
      transformation curves. The predicted curves agree with the experimental data.

PMID- 15501008
TI  - Normal flora: living vehicles for non-invasive protein drug delivery.
AB  - Feasibility to use probiotic bacteria as a living protein delivery system through
      oral route was assessed in vitro. Lactococcus lactis transformed with a plasmid
      to express and secret beta-lactamase was used to deliver beta-lactamase through
      Caco-2 monolayer, an intestine epithelium. Transport of beta-lactamase through
      Caco-2 monolayer was carried out in the transwells. The viability and integrity
      of the cell monolayers co-cultured with L. lactis was examined by trypan blue
      exclusion method and by measuring the transport of mannitol and propranolol as
      well as the transepithelial electrical resistance (TEER). Results show that it is
      feasible to use cell culture technique to evaluate the drug delivery by normal
      flora. The transport rate of beta-lactamase when delivered by L. lactis was 2.0
      +/- 0.1 x 10(-2)h(-1) (n = 9) and through free solution form was 1.0 +/- 0.1 x
      10(-2)h-1. When co-cultured with L. lactis, Caco-2 cell viability decreased to
      98, 96, and 94% at 6, 8, and 10h, respectively. Transport of mannitol through
      Caco-2 cell monolayer was significantly increased and the transport of
      propranolol through Caco-2 cell monolayer was significantly decreased in the
      presence of L. lactis. Increase in the amount of protein delivered is probably
      due to the concentrate of the protein by L. lactis on the monolayer (absorption
      surface) and the opening of the tight junction of Caco-2 monolayer by L. lactis.

PMID- 15501010
TI  - Improved photodynamic activity of porphyrin loaded into nanoparticles: an in vivo
      evaluation using chick embryos.
AB  - Hydrophobic porphyrins are potentially interesting molecules for the photodynamic
      therapy (PDT) of solid cancers or ocular vascularization diseases. Their
      pharmaceutical development is, however, hampered by their lipophilicity, which
      renders formulation difficult especially when intravenous administration is
      needed. Encapsulation of a lipophilic derivative of porphyrin, the meso-tetra(p
      hydroxyphenyl)porphyrin (p-THPP), into polymeric biodegradable poly(D,L-lactide
      co-glycolide) (PLGA) nanoparticles proved to enhance its photodynamic activity
      against mammary tumour cells when compared to free drug. In order to further
      investigate these carriers, the efficacy of the encapsulated drug was assessed on
      the chick embryo chorioallantoic membrane (CAM) model. First, we identified a
      suitable solvent for the drug in terms of p-THPP solubility and tolerability by
      chick embryos. This solution was used as a reference. Then, the fluorescence
      pharmacokinetics and the photodynamic effects of the porphyrin on CAM vessels
      were evaluated after intravenous administration of either a p-THPP solution (free
      drug) or the drug loaded into nanoparticles. The results showed that: (i) the
      drug remained longer in the vascular compartment when incorporated into
      nanoparticles and (ii) vascular effects of p-THPP after light irradiation were
      enhanced with nanoparticle carriers. These results are discussed taking into
      account the extravasation of intravascular circulating photosensitizers and its
      influence on PDT performance.

PMID- 15501012
TI  - Growth factors and muscle ageing.
AB  - Loss of muscle mass (sarcopenia) is one of the main problems associated with
      ageing as it has major health care as well as socioeconomic implications. The
      growth hormone (GH)/IGF-I axis is regarded as an important regulator of muscle
      mass. However, it is now appreciated that other tissues in addition to the liver
      express IGF-I and that there are local as well as systemic forms of IGF-I which
      have different functions. At least two different kinds of IGF-I that are
      expressed by skeletal muscle are derived from the IGF-I gene by alternative
      splicing, one of which is expressed in response to physical activity which has
      now been called 'mechano growth factor' (MGF). The other is similar to the
      systemic or liver type (IGF-IEa) and is important as the provider of mature IGF-I
      required for upregulating protein synthesis. MGF differs from systemic IGF-IEa in
      that it has a different peptide sequence which is responsible for replenishing
      the satellite (stem) cells in skeletal muscle. The ability to produce MGF
      declines with age, and this is commensurate with the decline in circulating GH
      levels. GH treatment up regulates the level of IGF-I gene expression in older
      people and when combined with resistance exercise more is spliced towards MGF and
      hence should improve the ability of muscle to respond to physical activity. The
      possibility of ameliorating sarcopenia using MGF is discussed.

PMID- 15501011
TI  - Controlled release of paclitaxel from microemulsion containing PLGA and
      evaluation of anti-tumor activity in vitro and in vivo.
AB  - The main objective of this study was to develop an optimal paclitaxel
      microemulsion prepared by self-microemulsifying drug delivery system (SMEDDS)
      which is a mixture of paclitaxel, tetraglycol, Cremophor ELP, and Labrafil 1944
      and a paclitaxel microemulsion containing poly(D,L-lactide-co-glycolide) (PLGA)
      in order to offer controlled release of paclitaxel. To achieve this goal,
      paclitaxel and PLGA were dissolved by solubilizer like tetraglycol. There was not
      observed any change in molecular weight of PLGA after being solubilized by
      tetraglycol. The droplet size for all of the formulation of microemulsion was
      found in the range of 45-270nm by dynamic light scattering (DLS). It was observed
      that the droplet size of microemulsion without PLGA was smaller than that of
      microemulsion containing PLGA by transmission electron microscopy (TEM). The
      droplet of microemulsion containing PLGA was almost of spherical shape with
      smooth surface and there was no aggregation or adhesion among droplet of
      microemulsion by atomic force microscopy (AFM). The release behaviour of
      paclitaxel from microemulsion containing PLGA having various molecular weights
      (8K, 33K, and 90K) exhibited a biphasic pattern characterized by a fast initial
      release during the first 48h, followed by a slower and continuous release for
      144h, in contrast that the release of paclitaxel from microemulsion without PLGA
      was finished during 24h. This result was identical with the result of anti-tumor
      activity in vitro of paclitaxel from microemulsion containing PLGA against human
      breast cancer cell line MCF7 and this formulation enhanced anti-tumor activity in
      vivo compared with microemulsion without PLGA against SKOV-3 human ovarian cancer
      cells bearing nude mice model.

PMID- 15501013
TI  - Impairment of gamma/delta T lymphocytes in elderly: implications for
      immunosenescence.
AB  - Gamma/delta T lymphocytes cells recognize the antigen in a non-classical way and
      are considered the third branch of the immune system devoted to defend the
      integrity of the body. Ageing is characterized by an impairment of the main way
      of protection (the adaptive branch) but, successfully aged people show
      compensatory mechanisms of defense such as proneness to inflammation. Moreover,
      very old subjects show an increased number of NK cells. We have previously
      demonstrated that gamma delta T lymphocytes are reduced in elderly. In the
      present paper we have studied some characteristics of these cells to evaluate the
      possibility that these cells might balance the decreased action of the adaptive
      branch in successfully aged people. Cytofluorimetric analysis of cells collected
      from young, old and centenarian subjects has been used to evaluate the ability of
      these cells to expand in vitro. Here we demonstrate that gamma delta T cells are
      impaired in the ability to proliferate to different stimuli such as isopentenyl
      pyrophoshate, that select gamma delta T lymphocytes bearing delta 2 chain, other
      than to phytohemagglutinin and anti-CD3 that are polyclonal activators. Moreover,
      we demonstrate that gamma delta T cells in aged and centenarians show an enhanced
      sensitivity to undergo apoptosis induced both by alpha-Fas and TNF-alpha. All
      together these data suggest that gamma delta T lymphocytes are impaired in
      elderly and suggest that the reduced ability to proliferate and the reduced
      number of circulating gamma delta T lymphocytes is due to the proneness to
      apoptosis. Finally on the basis of these data, we conclude that gamma delta T
      lymphocytes, do not participate in the remodeling of the immune system due to the
      reduction of classical T cell response and replacement by NK cells in elderly.

PMID- 15501014
TI  - Immunomodulating effect of influenza vaccination in the elderly differing in
      health status.
AB  - The aim of this study was to analyse whether split influenza vaccine may elicit
      NK cytotoxic response in the vaccinated elderly people and whether this effect
      may be maintained over few weeks after vaccination. It was also worth
      investigating the relation between NK activity in the vaccinated and specific
      immune protection against influenza and non-specific against other infections.
      Two groups of volunteers were vaccinated with trivalent split viron influenza
      vaccine in two consecutive seasons (1999/2000; 2000/2001). The elderly group
      consisted of 142 people (65-92 years old) in the first season and 110 in the
      second; while the young (16-44 years old) of 98 and 67 people, respectively. An
      analysis of NK cytotoxic activity had been done before vaccination, two days, one
      month and fifth months thereafter. The results revealed that vaccination with the
      influenza vaccine had an augmenting effect on NK activity, in all groups
      examined, in both epidemic seasons, visible at two days and 1 month after the
      vaccination. In the elderly high pre- and post-vaccination NK activity was
      related to higher titers of anti-hemagglutinin, better health status and lower
      incidence of all cause respiratory tract infections. At the second vaccination,
      most of the elderly with chronic medical conditions and high NK activity, who did
      not attain the protective level of anti-hemagglutinins in the first season,
      converted into the protected. High pre- and post-vaccination NK activity
      predisposes elderly people to the protective humoral anti-hemagglutinin response
      and gives better protection from respiratory tract infections.

PMID- 15501015
TI  - Anti-beta 2 glycoprotein I antibodies in centenarians.
AB  - BACKGROUND: Non-organ-specific autoantibodies are present in centenarians without
      evidence of autoimmune diseases but conflicting or no data on anti-phospholipid
      and anti-phospholipid binding proteins were reported. OBJECTIVE: To investigate
      the presence and antigen specificity of anti-phospholipid and anti-phospholipid
      binding proteins in centenarians. METHODS: Seventy-seven centenarians, 70 adult
      controls, 65 unselected elderly subjects, and 38 old SENIEUR volunteers were
      investigated. Anti-cardiolipin, anti-human beta 2 glycoprotein I, and lupus
      anticoagulant were detected. Antigen specificity was assayed against plates
      coated with anionic, neutral and cationic phospholipids and beta 2 glycoprotein I
      dependence was also evaluated. RESULTS: 54.3% of the centenarians were positive
      for IgG and 8.6% for IgM anti-beta 2 glycoprotein I antibodies, while only 20.7%
      centenarians were positive for anti-cardiolipin IgG and 2.59% for IgM; none
      resulted positive for lupus anticoagulant. Anti-cardiolipin positive sera cross
      reacted with negatively charged phospholipids and displayed decreased binding to
      serum-free cardiolipin-coated plates that was restored by human beta 2
      glycoprotein I or fetal calf serum. CONCLUSIONS: Centenarians display high
      reactivity against human beta 2 glycoprotein I but low binding to the bovine
      molecule in the anti-cardiolipin assay. In spite of the presence of antibodies
      comparable to those found in patients with the anti-phospholipid syndrome, no
      vascular events were reported suggesting the presence of unknown protective
      factors and/or the lack of triggering factors.

PMID- 15501016
TI  - Effect of age on Hsp72 expression in leukocytes of healthy active people.
AB  - Aging mammalians show reduced expression and induction of cytoprotective heat
      shock proteins in response to physiological stresses. Physical training can
      increase Hsp72 expression in young and old animals, but whether same adaptations
      can be observed in old people remains unknown. We hypothesized that the
      maintenance of physical activity during aging should preserve Hsp72 expression in
      leukocytes of elderly people. Intracellular and surface Hsp72 (the inducible form
      of Hsp70) expression in leukocytes as well as apoptotic and necrotic leukocytes
      were measured by flow cytometry at rest and after maximal incremental test on
      treadmill in the following groups: 8 young subjects (25.3+/-0.6 year, G25), 12
      sexagenarians (66.2+/-1 year, G65) and 9 octogenarians (82.2+/-1.2 year, G85),
      all physically active. Protein and lipid oxidation markers were also measured at
      rest and post-exercise. Results showed significant lower basal percentages of
      Hsp72-positive lymphocytes in G85 compared to G25. At rest, lower mean
      fluorescence intensity in Hsp72-positive monocytes was measured in G65 and G85
      compared to G25, and in granulocytes from G85 compared to G25. Maximal exercise
      test induced systemic oxidative-stress in the three groups but did not induce any
      increase in apoptotic or necrotic cells. We observed a significant increase in
      the percentage of Hsp72-positive lymphocytes from G85. This study showed that
      maintaining physical activity during aging can preserve the ability to induce
      Hsp72 in response to physiological stress.

PMID- 15501017
TI  - Characterization of the hsp70 response in lymphoblasts from aged and centenarian
      subjects and differential effects of in vitro zinc supplementation.
AB  - Human centenarians attract increasing interest as they hold some still undefined
      molecular mechanisms resulting in the achievement of exceptional old age. Recent
      data suggest the ability of centenarians to efficiently counter the increased
      cellular stress normally associated with ageing. The ubiquitous heat shock (HS)
      protein HSP70, expressed under the control of the heat shock transcription factor
      1 (HSF-1), is recognized as one of the main chaperones associated with cell
      protection against stresses. In fact, HSP70 protein induction by heat, a classic
      well characterized cellular stress, was recently reported to be reduced in cells
      of most aged humans but not in centenarians. In order to investigate the
      molecular basis of this feature, we analyzed in vitro the time course expression
      of the hsp70 gene and the activation of HSF-1 in heat treated Epstein Barr virus
      transformed B-lymphocytes of centenarians. Our study demonstrates that
      lymphoblasts from centenarians maintain the transcriptional response of hsp70
      gene to heat stress similar to young subjects. Such normal induction of hsp70 is
      associated to higher binding activity of HSF-1 that compensates an age-dependent
      delay in HSF-1 phosphorylation. Moreover, in vitro zinc supplementation had an
      age-dependent effect on hsp70 expression, indicating a role for this
      nutritionally important molecule and suggesting its involvement in cellular
      stress responses.

PMID- 15501018
TI  - Food consumption and individual lifespan of adults of the blowfly, Calliphora
      stygia: a test of the 'rate of living' theory of aging.
AB  - Following eclosion, adult Calliphora stygia were individually housed (at 22
      degrees C and 73% RH) in 125 ml plastic vials and provided with ad libitum access
      to either 0.125 or 0.2M sucrose as a food source and daily food consumption
      measured throughout their adult life. All blowflies were weighed daily and food
      consumed is determined by weighing individual food dishes. Blowflies provided
      with 0.125 M sucrose (N=59) consumed daily a significantly greater amount of the
      sucrose solution than those provided with 0.2M sucrose (n=55) such that the
      average rates of sucrose consumption were, respectively, 1.72 and 1.96 mg sucrose
      day(-1). There was no significant difference in the survival curves of the two
      populations with respective average (+/-SEM) lifespans being 25.4 (+/-1.2) and
      26.5 (+/-1.2) days. The respective ranges of individual lifespans were 4-53 and 5
      50 days. There was no statistically significant relationship between mass
      specific rate of sucrose consumption and lifespan in either population but there
      were highly significant (P<0.0001) correlations between lifetime sucrose
      consumption and lifespan in both groups of blowflies. These findings contradict
      the predictions of the 'rate of living' theory of aging. In both populations of
      blowflies, body mass and the rate of food consumption were relatively constant
      through the adult life of blowflies, except that a few days before death both
      sucrose consumption and body mass showed a dramatic decline.

PMID- 15501019
TI  - The reduction of protein intake observed in old rats depends on the type of
      protein.
AB  - Previous experiments have shown in Lou/c/jall rats growing old a deleterious
      reduction of protein intake, which occurs earlier in males than in females. We
      previously showed that this decrease could not be attributed to a loss of
      regulation of protein intake with age. Present studies were designed to
      investigate if the age-related decrease of protein intake was dependent on the
      type of protein used. In a first sectional study, adult, middle and old-aged
      Lou/c/jall rats were submitted to a self-selection procedure. They were fed
      successively with casein, whey protein and fish flour as protein. In a second
      longitudinal study, self-selected males and females were tested each 4 months (at
      3, 7, 11, 15, 19, 23 and 27 months of age) with only casein and whey protein as
      protein. In the two experiments, the type of dietary protein had an influence on
      the protein intake: when casein is offered, the well-established decrease in
      protein consumption was seen after 15 months of age in male groups. The
      introduction of whey protein induced maintenance of protein intake in old male
      groups at the level of female's protein intake. Moreover, young females showed an
      obvious preference for casein versus whey protein. This preference disappeared in
      old ages. These data showed that casein, even if it was an appropriate protein
      for young animals, could become inadequate for old animals and could result in a
      protein aversion in old rats. On the contrary, whey protein seemed to be a more
      appropriate protein than casein for old rats.

PMID- 15501020
TI  - Stressors and antistressors: how do they influence life span in HER-2/neu
      transgenic mice?
AB  - The purpose of this study is to investigate possible influences of different
      stressors (saline injections, light deprivation and constant light regimen) and
      geroprotectors (Epitalon and melatonin) on survivals of female HER-2/neu
      transgenic mice. We propose a semi-parametric model of heterogeneous mortality
      (frailty model) for the analysis of the experimental data. In this model, we
      assume that treatment influences parameters of both frailty distribution and
      baseline hazard. The unique design of the experiments makes it possible to
      compare the effects on survival produced by different treatments in terms of
      changes in population heterogeneity and underlying hazard. Parameters of the
      model help to describe the possible influences of various stressors,
      geroprotectors, and their dosage on the life span of laboratory animals. The
      proposed model helps to advance our understanding of the effects--such as
      debilitation, longevity hormesis and incomplete hormesis--which occur in the
      population as a result of different treatments.

PMID- 15501021
TI  - Comparison of thiol redox state of mitochondria and homogenates of various
      tissues between two strains of mice with different longevities.
AB  - The main purpose of this study was to determine if differences in life spans of
      two different strains of mice are associated with the thiol redox state of their
      tissues and mitochondria. A comparison, based on amounts of reduced and oxidized
      glutathione (GSH, GSSG) and reactive protein thiols, was made between short-lived
      SAM (P8) mice and the longer-lived C57BL/6 mice at 13 months of age. The average
      life span of the latter mouse strain is approximately 48% longer than the former
      strain. Analyses of plasma, tissue homogenates and mitochondria of liver, kidney,
      heart, brain and skeletal muscle indicated that, in general, amounts of GSH and
      reactive protein sulfhydryls and GSH:GSSG ratios were lower and concentrations of
      GSSG were higher in the SAM than the C57BL/6 mice. Differences in the redox state
      between the two strains were more consistent and pronounced in skeletal muscle
      than in other tissues, and in mitochondria than in their respective tissue
      homogenates. Overall, the results support the view that the shorter-lived SAM
      mice exhibit a relatively higher level of oxidative stress than the longer-lived
      C57BL/6 mice, which is consistent with the predictions of the oxidative stress
      hypothesis of aging. Intra-species comparisons may be useful for the
      identification of biochemical characteristics associated with the variations in
      life spans.

PMID- 15501022
TI  - Increased nuclear proteins in muscle satellite cells in aged animals as compared
      to young growing animals.
AB  - Evidence implies that satellite cells could play some limiting role in aged
      muscle undergoing repair or maintenance of mass, which is of potential clinical
      concern as this could contribute to sarcopenia. Further, insufficient information
      is available concerning the cellular mechanisms responsible for the lower rat
      satellite cell proliferation in old animals. Thus, it was hypothesized that the
      following proteins would be increased in nuclei of satellite cells from old rat
      skeletal muscle: the cyclin-dependent kinase (CDK) inhibitors p21(WAF1/CIP1) and
      p27(Kip1) as well as the transcription factors p53 and Forkhead box, subgroup O1
      (FOXO1). In addition, the NAD(+)-dependent histone deacetylase SIRT1, the
      mammalian ortholog of the yeast SIR2 (silence information regulator 2) and a
      member of the Sirtuin family, was hypothesized to decrease in satellite cell
      nuclei of old rats. Old satellite cells (30-months old) exhibited a lesser number
      of BrdU-positive cells as compared to satellite cells (3-months old) from young
      growing animals. Western blot analysis demonstrated that nuclei of old satellite
      cells accumulated the cell cycle inhibitors p21(WAF1/CIP1) and p27(Kip1). In
      addition, nuclear p53 and FOXO1 proteins were also higher in old satellite cells
      than in cells from young growing animals. These data indicated both
      p53/p21(WAF1/CIP1)- and FOXO1/p27(Kip1)-dependent pathways might contribute to
      the age-associated decrease in satellite cell proliferation. Cytoplasmic
      manganese superoxide dismutase (MnSOD), a gene driven by FOXO1, was higher in old
      satellite cells. Unexpectedly, nuclear SIRT1 was also increased in old satellite
      cells compared with satellite cells from young growing animals. The physiological
      significance of enhanced nuclear SIRT1 expression in old satellite cells remains
      elusive at this time. In summary, satellite cells in old rats have nuclear
      accumulation of proteins inhibiting the cell cycle as compared to young, growing
      animals.

PMID- 15501023
TI  - Protein nonenzymatic modifications and proteasome activity in skeletal muscle
      from the short-lived rat and long-lived pigeon.
AB  - What are the mechanisms determining the rate of animal aging? Of the two major
      classes of endothermic animals, bird species are strikingly long-lived compared
      to similar size mammalian counterparts. Since oxidative stress is causally
      related to the basic aging process, markers of different kinds of oxidative
      damage to proteins (glutamic semialdehyde, aminoadipic semialdehyde, N(epsilon)
      (carboxyethyl)lysine; N(epsilon)-(carboxymethyl)lysine, N(epsilon)
      (malondialdehyde)lysine and dinitrophenylhydrazyne-reactive protein carbonyls,
      peptidase activities of the proteasome, and amino acid and membrane fatty acyl
      composition were identified and measured in skeletal muscle from the short-lived
      rat (maximum life span, 4 years) and compared with the long-lived pigeon (maximum
      life span, 35 years). Skeletal muscle from pigeon showed significantly higher
      levels of glutamic semialdehyde, protein carbonyls (by western blot), N(epsilon)
      (carboxyethyl)lysine and N(epsilon)-(carboxymethyl)lysine. No differences were
      observed for aminoadipic semialdehyde, whereas the lipoxidation marker N(epsilon)
      (malondialdehyde)lysine displayed a significant low steady-state level, probably
      related with their significantly lower membrane unsaturation. The amino acid
      compositional analysis revealed that arginine, serine, threonine and methionine
      showed significantly lower levels in pigeon. Finally, pigeon samples showed also
      significantly lower levels of the peptidase activities of the proteasome. These
      results reinforces the role of structural components such as membrane
      unsaturation and protein composition in determining the longer maximum life span
      showed by birds compared with mammals of similar body size.

PMID- 15501024
TI  - Age-related changes in superoxide dismutase, glutathione peroxidase, catalase and
      xanthine oxidoreductase/xanthine oxidase activities in the rabbit cornea.
AB  - The activities of superoxide dismutase, glutathione peroxidase (GPX) and catalase
      -the enzymatic scavengers of reactive oxygen species and the activities of
      xanthine oxidoreductase and xanthine oxidase, an enzyme known to generate
      reactive oxygen species, were studied in the corneas of normal rabbit eyes of
      various ages (1 month--young eyes; 4-9.5 months--young adult eyes; 2.0-2.75 years
      -middle aged eyes; 3.0-5.0 years--aged eyes). The activities of GPX, superoxide
      dismutase, xanthine oxidoreductase and xanthine oxidase were investigated
      biochemically in the scraped corneal epithelium. Catalase activity was detected
      histochemically in the corneal epithelium and endothelium. The results show that
      young corneas revealed lower activities of all the antioxidant enzymes
      investigated than did young adult corneas, in which enzymatic activities reached
      their maximum. In middle-aged corneas, GPX and catalase activities remained
      approximately at the same levels as seen in young adult corneas, whereas
      superoxide dismutase activity was decreased. In aged corneas, the activities of
      all antioxidant enzymes were dramatically decreased or even lost (catalase
      activity in the corneal endothelium). In contrast, xanthine oxidoreductase
      activity only slightly decreased with age and the xanthine oxidase proportion of
      total xanthine oxidoreductase remained unchanged. GPX, superoxide dismutase and
      catalase are important antioxidant enzymes protecting the cornea against the
      oxidative damage. Because the activities of these enzymes are lower in young
      animals and greatly reduced in aged animals, it is suggested that young and
      particularly aged corneas might be more susceptible to oxidative stress than are
      young adult corneas. This presumption is supported by the fact that the
      activities of prooxidant enzymes (xanthine oxidoreductase/xanthine oxidase) are
      only slightly decreased in aged corneas as compared to young adult corneas so
      that some imbalance between antioxidant and prooxidant enzymes exists already in
      the normal aged corneas.

PMID- 15501025
TI  - Ageing affects the differentiation potential of human myoblasts.
AB  - The ageing process causes a reduction in the regenerative potential of skeletal
      muscles eventually leading to diminished muscle strength. In this work we
      investigated if ageing affects the excitation-contraction coupling mechanism in
      human myotubes derived from human satellite cells, thereby contributing to the
      loss in muscle strength in the aged. To test this hypothesis, satellite cells
      from differently aged donors were differentiated in vitro and the maturation of
      the excitation-contraction mechanism was followed by the videoimaging technique
      monitoring the efficiency of such a mechanism in generating intracellular calcium
      transients. Our experiments showed a delay in the establishment of the excitation
      contraction coupling mechanism depending on the age of the donor. Remarkably, the
      effect was reproducible in human satellite cells from a young donor aged in
      vitro, suggesting that the delayed functional maturation was strictly dependent
      on the number of satellite cell divisions and independent from the host
      environment.

PMID- 15501026
TI  - Increased plasma levels of soluble CD40, together with the decrease of TGF beta
      1, as possible differential markers of Alzheimer disease.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative illness and the most
      frequent cause of dementia in the elderly. The identification of activated
      microglia within neuritic plaques, coupled with the presence of numerous
      inflammatory proteins, suggests that inflammation is an integral part of the
      pathogenetic process in AD. In the present paper we have investigated the levels
      of circulating inflammatory mediators as potential AD biomarkers concentrating
      essentially on (a) soluble CD40 (sCD40), a member of the tumor necrosis factor
      receptor superfamily lacking the membrane-associated endodomain by alternative
      splicing, and (b) transforming growth factor (TGF)-beta 1, a cytokine deeply
      involved in AD and playing a protective role on CNS. Decrease of TGF-beta1 in AD
      patients could enhance the effects of pro-inflammatory cytokines produced by
      activated microglia as well as the expression of factors, such as the CD40/CD40
      ligand complex, by microglia and astrocytes. Total venous blood samples were
      obtained from 33 patients with clinical diagnosis of possible late-onset AD, 40
      healthy age-matched and 11 healthy young individuals. A significant increase of
      sCD40 levels plasma of AD patients versus healthy controls was measured,
      concomitantly with a decrease in TGF-beta1 concentration. These variations,
      however, showed no correlation with the expression of ApoE epsilon 4 allele,
      which was determined in order to assess the different frequency of this risk
      factor between AD and control groups. Since no comparable modifications were
      detected in patients affected by Parkinson's disease or non-AD-based dementia, we
      propose that sCD40 and TGF-beta1 plasma levels might represent possible
      differential biomarkers of AD, and be useful pre-mortem to support the clinical
      diagnosis of late-onset AD.

PMID- 15501027
TI  - Blood type B might imply longevity.
AB  - The aim of the present study was to investigate the association between blood
      groups and life expectancy. We compared frequencies of ABO blood group in 269
      centenarians (persons over 100 years) living in Tokyo and those in regionally
      matched controls (n=7153). Frequencies of blood types A, O, B, and AB in
      centenarians were 34.2, 28.3, 29.4, and 8.2%, respectively, while those in
      controls were 38.6, 30.1, 21.9, and 9.4%, respectively. Blood type B was observed
      more frequently in centenarians than in controls (chi(2)=8.41, P=0.04). This
      tendency also was true in comparison between centenarians and 118 elderly old
      individuals of the 7153. Approximate one-third of the centenarians were free from
      serious diseases such as malignancy. However, blood types were not associated
      with such medical records. Our findings suggest that blood type B might be
      associated with exceptional longevity. Responsible mechanisms need to be
      investigated.

PMID- 15501028
TI  - Interleukin 6-174 G/C promoter gene polymorphism and sporadic Alzheimer's
      disease: geographic allele and genotype variations in Europe.
AB  - The interleukin 6 (IL-6) gene in humans is located in the short arm of chromosome
      7 and has a-174 G/C polymorphism in its promoter region. The C allele at position
      174 in the promoter of the interleukin 6 (IL-6) gene has been associated with
      reduced gene expression and reduced plasma levels of IL-6. Given the supposed
      role of several inflammatory mediators in neurodegeneration and Alzheimer's
      disease (AD), the IL-6-174 G/C promoter polymorphism has been associated with AD
      with contrasting findings. First aim of the present study was to investigate
      whether there was evidence in Southern Italy of an association between the IL-6
      174 G/C promoter polymorphism and AD. Secondly, we also tested a possible effect
      of geographic genetic variations on existing reported associations comparing our
      results with the findings from published studies on other European populations.
      We examined apolipoprotein E (APOE) and IL-6-174 G/C promoter polymorphisms in a
      cohort of 168 sporadic AD patients and 220 sex- and age-matched nondemented
      controls from Southern Italy. No differences have been found in the IL-6-174 G/C
      promoter allele and genotype frequencies between AD patients and controls nor in
      early- and late-onset subsets of AD patients. No statistically significant
      differences in frequencies between IL-6-174 G/C promoter alleles and AD among
      APOE allele strata were found. Finally, comparing our results with the findings
      from other European populations, the IL-6*G/*G genotype frequency showed a
      statistically significant increasing trend from Northern to Southern regions of
      Europe in AD patients and controls, with a concomitant increase in IL-6*C/*G
      genotype frequency. Furthermore, an increasing geographical trend from North to
      South was found for the IL-6*G allele, with a concomitant inverse trend for IL
      6*C allele. We suggest that regional European differences in genotype and allele
      frequencies of the IL-6-174 G/C promoter polymorphism may explain in part
      controversial findings on this polymorphism in AD in various European studies.

PMID- 15501029
TI  - 2-(4-Methoxyphenoxy)-5-nitro-N-(4-sulfamoylphenyl)benzamide activates Kir6.2/SUR1
      K(ATP) channels.
AB  - 2-(4-Methoxyphenoxy)-5-nitro-N-(4-sulfamoylphenyl)benzamide and close analogues
      inhibit glucose stimulated insulin release through activation of Kir6.2/SUR1
      K(ATP) channels of beta cells.

PMID- 15501030
TI  - In vitro advanced antimycobacterial screening of cobalt(II) and copper(II)
      complexes of fluorinated isonicotinoylhydrazones.
AB  - The in vitro antimycobacterial activity of cobalt(II) and copper(II) complexes of
      some fluorinated isonicotinoylhydrazones was evaluated in a TB-infected
      macrophage model; all metalcomplexes exhibited excellent activity against
      Mycobacterium tuberculosis Erdman growing within macrophages, at concentrations
      much lower than in culture media. Moreover complexes 1b and 2a displayed EC(99)
      values lower than that of the parent-drug, isoniazid. In addition, all tested
      metalchelates significantly inhibited the growth of single-drug-resistant M.
      tuberculosis strains; complexes 1a and 2a also possessed moderate activity
      against Mycobacterium avium complex.

PMID- 15501031
TI  - Expanding the scope of site-specific protein biotinylation strategies using small
      molecules.
AB  - We present a new approach to site-specifically biotinylate protein in a cell-free
      protein synthesis system with puromycin-containing small molecules. With this new
      method, biotinylated proteins were generated from the DNA templates in a matter
      of hours, making it useful for protein microarray generation. We also validated
      that the method is compatible with other high-throughput cloning/proteomics
      methods.

PMID- 15501032
TI  - Haloperidol: towards further understanding of the structural contributions of its
      pharmacophoric elements at D2-like receptors.
AB  - An attempt to understand the pharmacophore-relevant position of the alcoholic
      moiety in haloperidol and the contributions of other pharmacophoric elements led
      to the re-synthesis of its tropane analogue (compound 2). An analysis of the
      binding data suggests that haloperidol binds to the DA receptors with the OH
      group in the axial position and the OH group, while not essential for binding,
      enhances binding especially at the D2 receptor. It also became clear that
      shortening the butyrophenone chain not only reduces binding affinity at the DA
      receptors but eliminates subtype selectivity.

PMID- 15501033
TI  - Site-specific PEGylation of proteins containing unnatural amino acids.
AB  - Here, we report a generally applicable PEGylation methodology based on the site
      specific incorporation of para-azidophenylalanine into proteins in yeast. The
      azido group was used in a mild [3+2] cycloaddition reaction with an alkyne
      derivatized PEG reagent to afford selectively PEGylated protein. This strategy
      should be useful for the generation of selectively PEGylated proteins for
      therapeutic applications.

PMID- 15501034
TI  - Alpha-beta chimeric oligo-DNA bearing intercalator-conjugated nucleobase inside
      the linker sequence remarkably improves thermal stability of an alternate
      stranded triple helix.
AB  - Novel alpha-beta chimeric oligodeoxynucleotides bearing an intercalator
      conjugated nucleobase located at the internal 4-nt linker region were
      synthesized, and their triplex-stabilizing property was examined. The triple
      helical DNA formed between the modified chimera DNA and double-stranded DNA
      exhibited remarkable thermal stability; however, the position of the intercalator
      conjugated nucleobase had little influence on the stability. Among the examined,
      modified chimera DNA bearing the two intercalator-conjugated nucleobases at
      adjacent positions exhibited the highest stability.

PMID- 15501035
TI  - Novel 2-oxoimidazolidine-4-carboxylic acid derivatives as hepatitis C virus NS3
      4A serine protease inhibitors: synthesis, activity, and X-ray crystal structure
      of an enzyme inhibitor complex.
AB  - Synthesis and HCV NS3 serine protease inhibitory activity of some novel 2
      oxoimidazolidine-4-carboxylic acid derivatives are reported. Inhibitors derived
      from this new P2 core exhibited activity in the low microM range. X-ray structure
      of an inhibitor, 15c bound to the protease is presented.

PMID- 15501036
TI  - Synthesis and cytotoxic activity of substituted luotonin A derivatives.
AB  - Luotonin A is a cytotoxic alkaloid that has been shown to inhibit topoisomerase I
      via stabilization of the binary complex topoisomerase-DNA in the same fashion as
      camptothecin. The synthesis and the cytotoxic activity on the lung carcinoma cell
      line H460 of a series of derivatives of Luotonin A is reported. The compounds
      inhibit topoisomerase I but show weak cytotoxic activity, thus confirming the
      peculiarity of ring E of camptothecin for antitumor activity.

PMID- 15501037
TI  - Carbonic anhydrase inhibitors. Interaction of isozymes I, II, IV, V, and IX with
      phosphates, carbamoyl phosphate, and the phosphonate antiviral drug foscarnet.
AB  - A detailed inhibition study of five carbonic anhydrase (CA, EC 4.2.1.1) isozymes
      with inorganic phosphates, carbamoyl phosphate, the antiviral phosphonate
      foscarnet as well as formate is reported. The cytosolic isozyme hCA I was weakly
      inhibited by neutral phosphate, strongly inhibited by carbamoyl phosphate (K(I)
      of 9.4 microM), and activated by hydrogen- and dihydrogenphosphate, foscarnet and
      formate (best activator foscarnet, K(A)=12 microM). The cytosolic isozyme hCA II
      was weakly inhibited by all the investigated anions, with carbamoyl phosphate
      showing a K(I) of 0.31 mM. The membrane-associated isozyme hCA IV was the most
      sensitive to inhibition by phosphates/phosphonates, showing a K(I) of 84 nM for
      PO(4)(3-), of 9.8 microM for HPO(4)(2-), and of 9.9 microM for carbamoyl
      phosphate. Foscarnet was the best inhibitor of this isozyme (K(I) of 0.82 mM)
      highly abundant in the kidneys, which may explain some of the renal side effects
      of the drug. The mitochondrial isozyme hCA V was weakly inhibited by all
      phosphates/phosphonates, except carbamoyl phosphate, which showed a K(I) of 8.5
      microM. Thus, CA V cannot be the isozyme involved in the carbamoyl phosphate
      synthetase I biosynthetic reaction, as hypothesized earlier. Furthermore, the
      relative resistance of CA V to inhibition by inorganic phosphates suggests an
      evolutionary adaptation of this mitochondrial isozyme to the presence of high
      concentrations of such anions in these energy-converting organelles, where high
      amounts of ATP are produced by ATP synthetase, from ADP and inorganic phosphates.
      The transmembrane, tumor-associated isozyme hCA IX was on the other hand slightly
      inhibited by all these anions.

PMID- 15501038
TI  - Carbonic anhydrase inhibitors: inhibition of the membrane-bound human isozyme IV
      with anions.
AB  - The membrane-associated human isozyme of carbonic anhydrase, hCA IV, has been
      investigated for its interaction with anion inhibitors, for the CO(2) hydration
      reaction catalyzed by this enzyme. Surprisingly, halides were observed to act as
      potent hCA IV inhibitors, with inhibition constants in the range of 70-90 microM,
      although most of these ions, and especially fluoride, the best hCA IV inhibitor
      among the halides, are weak inhibitors of other isozymes, such as hCA I, II and
      V. The metal poisons cyanate, cyanide and hydrogen sulfide were weaker hCA IV
      inhibitors (K(i)'s in the range of 0.6-3.9 mM), whereas thiocyanate, azide,
      nitrate and nitrite showed even weaker inhibitory properties (K(i)'s in the range
      of 30.8-65.1 mM). Sulfate was a good hCA IV inhibitor (K(i) of 9 mM), although it
      is a much weaker inhibitor of isozymes I, II, V and IX. Excellent hCA IV
      inhibitory properties showed sulfamic acid, sulfamide, phenylboronic acid and
      phenylarsonic acid, with K(i)'s in the range of 0.87-0.93 microM, whereas their
      affinities for the other investigated isozymes were in the millimolar range. The
      interaction of some anions with the mitochondrial isozyme hCA V has also been
      investigated for the first time here. It has been observed that among all these
      isozymes, hCA V has the lowest affinity for bicarbonate and carbonate (K(i)'s in
      the range of 82-95 mM), which may represent an evolutionary adaptation of this
      isozyme to the rather alkaline environment (pH 8.5) within the mitochondria,
      where hCA V plays important functions in some biosynthetic reactions involving
      carboxylating enzymes (pyruvate carboxylase and acetyl coenzyme A carboxylase).
      There are important differences of affinity for anions between the two membrane
      associated isozymes, hCA IV and hCA IX.

PMID- 15501039
TI  - Carbonic anhydrase inhibitors: synthesis and inhibition of cytosolic/tumor
      associated carbonic anhydrase isozymes I, II, and IX with sulfonamides derived
      from 4-isothiocyanato-benzolamide.
AB  - A series of sulfonamides incorporating 4-thioureido-benzolamide moieties have
      been prepared from aminobenzolamide and thiophosgene followed by the reaction of
      the thiocyanato intermediate with aliphatic/aromatic amines or hydrazines. The
      new derivatives have been investigated as inhibitors of the zinc enzyme carbonic
      anhydrase (CA, EC 4.2.1.1), and more precisely of the cytosolic isozymes hCA I
      and II, as well as the tumor-associated isozyme hCA IX (all of human origin). The
      new compounds showed excellent inhibitory properties against all three isozymes
      with inhibition constants in the range of 0.6-62 nM against hCA I, 0.5-1.7 nM
      against hCA II and 3.2-23 nM against hCA IX, respectively. These derivatives are
      interesting candidates for the development of novel therapies targeting hypoxic
      tumors.

PMID- 15501040
TI  - Carbonic anhydrase inhibitors. Design of anticonvulsant sulfonamides
      incorporating indane moieties.
AB  - A series of aromatic sulfonamides incorporating indane moieties were prepared
      starting from commercially available 1- and 2-indanamine, and their activity as
      inhibitors of two carbonic anhydrase (CA, EC 4.2.1.1) isozymes, hCA I and II was
      studied. The new sulfonamides incorporating acetamido, 4-chloro-benzoyl,
      valproyl, tetra-, and pentafluorobenzoyl moieties acted as very potent inhibitors
      of the slow red blood cell isozyme hCA I (K(i)s in the range of 1.6-8.5 nM),
      which usually has a lower affinity for such inhibitors, as compared to isozyme
      II. Some derivatives also showed excellent hCA II inhibitory properties (K(i)s in
      the range of 2.3-12 nM), but the anticonvulsant activity of these sulfonamides
      was rather low as compared to that of other sulfonamide/sulfamate CA inhibitors,
      such as methazolamide. Furthermore, the 2-amino/acetamido-indane-5-sulfonic acids
      prepared during this work also showed interesting CA inhibitory properties, with
      inhibition constants in the range of 43-89 nM against the two isozymes, being
      among the most potent sulfonic acid CA inhibitors reported so far.

PMID- 15501041
TI  - Synthesis of new N-(2-(trifluoromethyl)pyridin-4-yl)anthranilic acid derivatives
      and their evaluation as anticancer agents.
AB  - The N-(2-(trifluoromethyl)pyridin-4-yl)anthranilic acid 6 and a series of its
      ester and amide derivatives were synthesized and evaluated for their in vitro
      cytotoxic activity against human cancer cells. Ester derivatives 13 and 18
      exhibited potent growth inhibitory activity with GI(50) values at nanomolar
      concentrations. Among amide derivatives, N-anthraniloylglycinate 19 shown
      moderate inhibitory activity in the full panel cancer cell line screening.

PMID- 15501042
TI  - Urea derivatives of STI571 as inhibitors of Bcr-Abl and PDGFR kinases.
AB  - The constitutively active Abl kinase activity of the Bcr-Abl oncoprotein is
      causative for chronic myelogenous leukemia. Urea derivatives, structurally
      related to the therapeutic agent STI571, have been identified, which potently
      inhibit the tyrosine kinase activity of recombinant Abl. In particular a
      dimethylamino-aniline derivative (18) inhibited c-Abl transphosphorylation with
      an IC(50) value of 56 nM. Although this activity was not translated into cellular
      activity against the constitutively activated oncogenic Bcr-Abl, a number of
      compounds from this series potently inhibited cellular PDGFR autophosphorylation.
      It was also possible to differentiate between c-Abl and PDGFR kinase inhibition,
      with compound 22 being selective towards Abl and 23 selective for PDGFR.

PMID- 15501043
TI  - Inactivation of S-adenosylhomocysteine hydrolase with haloethyl and
      dihalocyclopropyl esters derived from homoadenosine-6'-carboxylic acid.
AB  - In a search for new inhibitors that exploit 5'-6' 'hydrolytic activity' of AdoHcy
      hydrolase, a new series of haloethyl and dihalocyclopropyl esters 2-3 were
      designed and their interaction with the enzyme studied. Incubation of the enzyme
      with 2-3 resulted in time- and concentration-dependent inactivation of AdoHcy
      hydrolase as well as almost total depletion of its NAD(+) content. Further
      results indicated that the 'oxidative' but not the 'hydrolytic' activity was
      involved in the inactivation process.

PMID- 15501044
TI  - Inactivation of human S-adenosylhomocysteine hydrolase by covalent labeling of
      cysteine 195 with thionucleoside derivatives.
AB  - A new series of 5'-thioadenosine derivatives 1-4 were synthesized for selectively
      targeting (195)Cys of human AdoHcy hydrolase. Their incubation with the enzyme
      resulted in time- and concentration-dependent inactivation, without major
      modifications of the NAD(+)/NADH ratio. The electrospray mass analysis of the
      inactivated enzyme with 1, 2, 3, and 4b showed that inhibition was accompanied by
      the formation of a specific and covalent labeling of each AdoHcy hydrolase
      subunit. Proteolytic cleavage (endo-Lys-C) and subsequent peptide
      characterization of the labeled enzyme revealed that (195)Cys was the residue
      modified during the inactivation process.

PMID- 15501045
TI  - Synthesis of small molecule CDC25 phosphatases inhibitors.
AB  - A targeted library of small molecules has been prepared to optimize the
      biological activity of BN82002, our initial lead compound, recently described as
      an original inhibitor of CDC25 phosphatases. Some of these compounds inhibit
      CDC25 in the micromolar range and therefore reinforce the interest of CDC25 as an
      anticancer target.

PMID- 15501046
TI  - Design, synthesis, and evaluation of hexahydrobenz[f]isoquinolines as a novel
      class of dopamine 3 receptor ligands.
AB  - We previously identified hexahydrobenz[f]isoquinoline (4a) as a new class of
      dopamine 3 receptor (D(3)) ligand. Herein, we described the design, synthesis,
      and preliminary structure-activity relationships of new analogues of 4a as a
      novel class of D(3) ligands. Among these new analogues, compound 4 h is a potent
      D(3) ligand (K(i)=6.1 nM) and has a selectivity of 133-fold between D(3)- and
      D(2)-like receptors, and of 163-fold between D(3)- and D(1)-like receptors,
      respectively. Thus, compound 4 h represents a promising new lead compound for
      further design and optimization toward achieving highly potent and selective D(3)
      ligands.

PMID- 15501047
TI  - Chlorothiophenecarboxamides as P1 surrogates of inhibitors of blood coagulation
      factor Xa.
AB  - Neutral chlorothiophenecarboxamides bearing an amino acid and a substituted
      aniline were synthesized and investigated for their factor Xa inhibitory activity
      in vitro. From selected 2-methylphenyl morpholinones the solution properties were
      determined. The most soluble and active compounds were then investigated in
      different animal species to compare the pharmacokinetic parameters. This led to a
      potent, water soluble and orally bioavailable candidate for further development:
      EMD 495235.

PMID- 15501048
TI  - Homology model of the multidrug transporter LmrA from Lactococcus lactis.
AB  - LmrA is an ATP dependent multidrug transporter from Lactococcus lactis conferring
      antibiotic resistance to 17 out of 21 most frequently administered antibiotics.
      Starting from the dimeric crystal structure of Vc-MsbA, we built two homology
      models, with NBD:NBD interfaces reflecting the nonenergized and energized state,
      respectively. The TMD:TMD topology of the dimer is consistent with the previously
      obtained substrate photoaffinity labeling pattern suggesting binding of
      substrates at the TMD:TMD interface involving helix 3 of one monomer and helices
      5 and 6 of the other monomer.

PMID- 15501049
TI  - Synthesis and alpha4beta2 nicotinic affinity of 2-pyrrolidinylmethoxyimines and
      prolinal oxime ethers.
AB  - Homochiral E and Z isomers of N-methylprolinal O-isopropyloxime and (1-methyl-2
      pyrrolidinyl)methoxyimines were synthesized as candidate bioisosteres of nicotine
      and its isoxazolic analogue ABT 418. Two of them, namely (S)-2
      isopropylideneaminooxymethyl- and (Z)-(S)-2-ethylideneaminooxymethyl-1
      methylpyrrolidine, proved to bind at alpha4beta2 nicotinic acetylcholine receptor
      with submicromolar affinity and remarkable selectivity over alpha7 and muscarinic
      receptors thus supporting the hypothesized bioisosteric relationship between
      their methyloxyimino group and the aromatic heterocycles of the reference
      ligands.

PMID- 15501050
TI  - Screening of antimicrobial activity of diarylamines in the 2,3,5
      trimethylbenzo[b]thiophene series: a structure-activity evaluation study.
AB  - Gram positive (Bacillus cereus, B. subtilis), Gram negative (Pseudomonas
      aeruginosa, Escherichia coli) bacteria, and Candida albicans as a representative
      of fungi were used for screening the in vitro antimicrobial activity of
      diarylamines in the 2,3,5-trimethylbenzo[b]thiophene series bearing different
      substituents, synthesized by us using the palladium-catalyzed C-N coupling
      methodology. The minimal inhibitory concentration (MIC) and structure-activity
      relationships (SARs) were evaluated.

PMID- 15501051
TI  - Ring nitrogen-substituted non-steroidal estrogens: pyridine and pyrimidine
      analogs of the phenol in deoxyhexestrol experience resonance constraints on
      preferred ligand conformation.
AB  - To develop compounds selective for estrogen receptor beta (ERbeta), we
      substituted hydroxypyridine and pyrimidine heteroaryl groups for the
      characteristic phenol ring of non-steroidal estrogens. The unexpectedly low
      affinity showed by some of these compounds is ascribed, in part, to a resonance
      enforced conformational constraint that prevents their optimal accommodation in
      the ER ligand binding pocket.

PMID- 15501052
TI  - Synthesis and biological studies of 1-amino beta-carbolines.
AB  - A selection of 1-amino-substituted beta-carbolines have been prepared by
      amination of 1-chloro-beta-carboline as simple mimics of manzamine A and
      chloroquine and their intercalating ability, anticancer and antimalarial activity
      were studied.

PMID- 15501053
TI  - Evaluation of by disubstituted acridone derivatives as telomerase inhibitors: the
      importance of G-quadruplex binding.
AB  - The synthesis and evaluation of a group of 2,6-, 2,7- and 3,6-bis-aminoalkylamido
      acridones are reported, which show a similar level of activity against telomerase
      in vitro compared to their acridine counterparts. Computer modelling and
      calculations of relative binding energies suggest an equivalent binding mode to
      human intramolecular G-quadruplex DNA, but with significantly reduced affinity,
      as a result of the limited delocalisation of the acridone chromophore compared to
      the acridine system. Thermal melting studies on acridone and acridine quadruplex
      complexes using a FRET approach support these predictions. Long-term cell
      proliferation studies at sub-cytotoxic doses with two representative acridones
      using the SKOV3 cell line, show that neither compound produces growth arrest, in
      contrast with the effects produced by the tri-substituted acridine compound BRACO
      19. It is concluded that telomerase inhibitory activity is a necessary though by
      itself insufficient property in order for cellular growth arrest to occur at sub
      toxic concentrations, and that tight quadruplex binding is also required.

PMID- 15501054
TI  - 3-O-Glutaryl-dihydrobetulin and related monoacyl derivatives as potent anti-HIV
      agents.
AB  - 3-O-Acyl-betulin and -dihydrobetulin derivatives were prepared and evaluated for
      anti-HIV activity. 3-O-Glutaryl-dihydrobetulin (17) demonstrated extremely potent
      anti-HIV activity with an EC(50) value of 2 x 10(-5) microM and a TI value of
      1.12 x 10(6). 3-O-(3',3'-Dimethylsuccinyl)- and 3-O-(3',3'-dimethylglutaryl)
      dihydrobetulins (15, 16) were also potent anti-HIV compounds with EC(50) values
      of 0.0017 and 0.0013 microM, respectively, and TI values of 16,160 and 19,530,
      respectively.

PMID- 15501055
TI  - Anti-AIDS agents. Part 62: anti-HIV activity of 2'-substituted 4-methyl-3',4'-di
      O-(-)-camphanoyl-(+)-cis-khellactone (4-methyl DCK) analogs.
AB  - Four 4-methyl-3',4'-di-O-(-)-camphanoyl-(+)-cis-khellactone (4-methyl DCK)
      analogs (7a-d) with different alkyl substituents at the 2'-position were
      synthesized and evaluated for inhibition of HIV-1 replication in H9 lymphocytes.
      2'-Methyl-2'-ethyl-4-methyl DCK (7b) was more potent (EC(50)=0.22 microM, TI>175)
      than the other three compounds (7a, 7c, and 7d), but significantly less potent
      than 4-methyl DCK (2, EC(50)=0.0059 microM, TI>6600). The bioassay results
      indicated that the 2'-substituents had a strong effect on the anti-HIV activity,
      and gem-dimethyl substitution at the 2'-position was greatly preferable to larger
      alkyl substituents or hydrogen atoms.

PMID- 15501056
TI  - Determination of the free radical scavenging activity of dihydropyran-2,4-diones.
AB  - The antioxidant activities of four synthetic dihydropyran-2,4-diones have been
      established through the determination of their abilities to inhibit free radicals
      using DPPH(*) as the stable radical. Whilst all of the compounds exhibited high
      inhibition percentages, the most active member of the group was 6-phenyl
      dihydropyran-2,4-dione. The antioxidant activity of the dihydropyran-2,4-diones
      is reported here for the first time and extends our knowledge of the range of
      valuable biological activities associated with this group of compounds.

PMID- 15501057
TI  - The impact of spacer structure on 5-HT7 and 5-HT1A receptor affinity in the group
      of long-chain arylpiperazine ligands.
AB  - New cis-, trans-2-butene and 1,2-bismethylbenzene analogues of MM77 and NAN-190
      (1-[4-[4-(2-methoxyphenyl)-piperazin-1-yl]-butyl]-pyrrolidine-2,5-dione and
      isoindole-1,3-dione, respectively) were synthesized. The differences in their in
      vitro affinity for serotonin 5-HT(7) and 5-HT(1A) receptors were explained using
      a conformational analysis. A bioactive conformation of those compounds for the 5
      HT(7) receptor, different from that established for 5-HT(1A), was proposed.

PMID- 15501058
TI  - Allosteric potentiators of the metabotropic glutamate receptor 2 (mGlu2). Part 2:
      4-thiopyridyl acetophenones as non-tetrazole containing mGlu2 receptor
      potentiators.
AB  - We have identified and synthesized a series of 4-thiopyridyl acetophenones as
      positive allosteric potentiators of the metabotropic glutamate receptor 2.
      Structure-activity relationship studies directed toward replacement of the
      tetrazole in the initial lead led to the discovery of 16 (EC(50)=340 nM), which
      showed improved brain penetration over the initial lead.

PMID- 15501059
TI  - Synthesis and biological evaluation of an orally active ghrelin agonist that
      stimulates food consumption and adiposity in rats.
AB  - 2-(2-Amino-2-methyl-propionylamino)-5-phenyl-pentanoic acid [1-[1-(4-methoxy
      phenyl)-1-methyl-2-oxo-2-pyrrolidin-1-yl-ethyl]-1H-imidazol-4-yl]-amide
      (LY444711, 6) is an orally active ghrelin agonist that binds with high affinity
      to and is a potent activator of the growth hormone secretagogue receptor 1a (GHS
      R1a) receptor. In rat models of feeding behavior and pharmacology, 6 creates a
      positive energy balance and induces adiposity by stimulating food consumption and
      sparing fat utilization. As an orally active ghrelin agonist, 6 represents a new
      pharmacological tool to investigate the orexigenic role of ghrelin in regulating
      energy homeostasis.

PMID- 15501060
TI  - Farnesyl protein transferase inhibitors targeting the catalytic zinc for enhanced
      binding.
AB  - Successful efforts to make farnesyl transferase (FT) inhibitors with
      appropriately tethered ligands designed to interact with a catalytic zinc that
      exist in the enzyme have been realized. Thus, by introducing either a
      pyridylmethylamino or propylaminolimidazole amide moieties off the 2-position of
      the piperidine ring, FT inhibitors with activities in the picomolar range have
      been achieved as exemplified by compounds 12a and 12b. An X-ray structure of 11b
      bound to FT shows the enhanced activity is a result of interacting with the
      active-site zinc.

PMID- 15501061
TI  - Tetrahydroisoquinoline derivatives as melatonin MT2 receptor antagonists.
AB  - A series of tetrahydroisoquinolines has yielded potent MT(2) receptor
      antagonists, which are selective versus the MT(1) receptor.

PMID- 15501062
TI  - Synthesis and biological evaluation of novel taxoids designed for targeted
      delivery to tumors.
AB  - The use of drug-antibody conjugates affords a method for the targeted delivery of
      anticancer drugs specifically to cancer cells. Monoclonal antibodies alone
      usually do not possess high therapeutic efficacy, however, they are capable of
      targeting tumor markers selectively. We have prepared taxoids with significantly
      higher cytotoxicity than paclitaxel and docetaxel. These taxoids now meet the
      high potency required for use in a targeted-delivery approach using monoclonal
      antibodies. The synthesis and biological evaluation of these taxoids are
      reported.

PMID- 15501063
TI  - Binding of an aminoacridine derivative to a GAAA RNA tetraloop.
AB  - RNA tetraloops are common secondary structural motifs in many RNAs, especially
      ribosomal RNAs. There are few studies of small molecule recognition of RNA
      tetraloops although tetraloops are known to interact with RNA receptors and
      proteins, and to form nucleation sites for RNA folding. In this paper, we
      investigate the binding of neomycin, kanamycin, 2,4-diaminoquinazoline,
      quinacrine, and an aminoacridine derivative (AD1) to a GAAA tetraloop using
      fluorescence spectroscopy. We have found that AD1 and quinacrine bind to the GAAA
      tetraloop with the highest affinity of the molecules examined. The equilibrium
      dissociation constant of the AD1-GAAA tetraloop complex was determined to be 1.6
      microM. RNase I and lead acetate footprinting experiments suggested that AD1
      binds to the junction between the loop and stem of the GAAA tetraloop.

PMID- 15501064
TI  - Synthesis and inhibitory effects of pinosylvin derivatives on prostaglandin E2
      production in lipopolysaccharide-induced mouse macrophage cells.
AB  - A series of natural stilbenoids, pinosylvin and its derivatives, were synthesized
      and evaluated for the inhibitory activity of prostaglandin E(2) production in
      lipopolysaccharide-induced RAW 264.7 cells. Potential inhibitors, including 3,5
      dimethoxy-trans-stilbene and 3-hydroxy-5-benzyloxy-trans-stilbene, have been
      newly identified, and thus providing chemical leads for the further development
      of anti-inflammatory or cancer chemopreventive agents.

PMID- 15501065
TI  - Bridgehead modification of trihalocycloheptabenzopyridine leads to a potent
      farnesyl protein transferase inhibitor with improved oral metabolic stability.
AB  - Modification of the ethano bridge of the core structure of the antitumor agent,
      SARASAR (SCH66336) with concomitant introduction of a sulfonamide moiety off the
      distal piperidine afforded inhibitor 9-(S-), a compound with greatly improved PK
      profile. Other compounds with enhanced FPTase inhibitory activity were obtained
      as exemplified by amide 10-(S-) and urea 11-(S-): these compounds demonstrated
      activity in picomolar range.

PMID- 15501066
TI  - Syntheses of photolabile novobiocin analogues.
AB  - Novobiocin was recently shown to inhibit Hsp90 through a previously unrecognized
      C-terminal ATP binding site. Although the N-terminal region of Hsp90 has been
      solved by X-ray crystallography, the C-terminal region has not. In an effort to
      elucidate the C-terminal binding site of Hsp90, four photolabile analogues of
      novobiocin were prepared.

PMID- 15501067
TI  - Synthesis of analogs of (1,4)-3- and 5-imino oxazepane, thiazepane, and diazepane
      as inhibitors of nitric oxide synthases.
AB  - A series of 3- and 5-imino analogs from oxazepane, thiazepane, and diazepane was
      prepared and evaluated as inhibitors of human nitric oxide synthesis (NOS). The
      most potent iNOS inhibitor was the thiazepane analog 25 (IC(50) = 0.19 microM).

PMID- 15501068
TI  - Novel retinoid X receptor (RXR) antagonists having a dicarba-closo-dodecaborane
      as a hydrophobic moiety.
AB  - We designed and synthesized novel retinoid X receptor (RXR)-selective antagonists
      bearing a carborane moiety. Compounds 8a-d or 9a-d themselves have no
      differentiation-inducing activity toward HL-60 cells and no inhibitory activity
      towards a retinoic acid receptor (RAR) agonist. However, they inhibit the
      synergistic activity of an RXR agonist, PA024, in the presence of Am80 on the
      cell differentiation of HL-60. Transactivation assay using RARs and RXRs
      suggested that the inhibitory activity of 9b resulted from the selective
      antagonism at the RXR site of RXR-RAR heterodimers.

PMID- 15501069
TI  - Biological evaluation of novel estrogen-platinum(II) hybrid molecules on uterine
      and ovarian cancers-molecular modeling studies.
AB  - We have recently reported the synthesis of a series of original 17beta-estradiol
      linked platinum(II) hybrid molecules. The biological activity of these compounds
      was evaluated in vitro on estrogen dependent and independent (ER(+) and ER(-))
      human uterine and ovarian cancers. The hybrid molecules present higher affinity
      than that of 17beta-estradiol for the estrogen receptor alpha (ERalpha). The
      cytotoxicity and the affinity of the hybrid molecules are explained using
      molecular modeling analysis. This study further confirms that the derivatives
      made of a 2-(2'-aminoethyl)pyridine ligand displayed superior activity against
      the cell lines particularly when the connecting arm is 8-10 carbon atoms long.
      Molecular modeling shows that a long side chain can facilitate the access of the
      platinum(II) moiety to DNA. The novel compounds also prove to be moderately
      cytotoxic against platinum resistant endometrial and ovarian cancer cell lines.

PMID- 15501070
TI  - Identification of peptidomimetic HTLV-I protease inhibitors containing
      hydroxymethylcarbonyl (HMC) isostere as the transition-state mimic.
AB  - Towards the development of chemotherapy for the infection by human T-cell
      leukemia virus type I (HTLV-I), we have established evaluation systems for HTLV-I
      protease (PR) inhibitors using both recombinant and chemically synthesized HTLV-I
      PRs. Newly synthesized substrate-based inhibitors containing
      hydroxymethylcarbonyl (HMC) isostere showed potent anti-HTLV-I PR activity.

PMID- 15501071
TI  - A nonhydrolyzable analogue of phosphotyrosine, and related aryloxymethano- and
      aryloxyethano-phosphonic acids as motifs for inhibition of phosphatases.
AB  - Nonhydrolyzable analogues of both stereoisomers of phosphotyrosine, and a series
      of related aryloxy (or thio) methyl and aryloxy (or thio) ethyl phosphonic acids
      of the general formula RX-(CH(2))(n)-PO(3)H(2) (where X=O or S and n=1 or 2),
      have been tested as nonhydrolyzable mimetics of phosphatase substrates. These
      compounds were tested against a panel of phosphatases (two alkaline phosphatases,
      a protein-tyrosine phosphatase, and two serine/threonine phosphatases) with
      different active site motifs. The compounds exhibit competitive inhibition toward
      all enzymes tested, with the best inhibition expressed toward the Ser/Thr
      phosphatases. The stereoisomers of the phosphotyrosine analogues exhibited an
      unexpected difference in their inhibitory properties toward the protein-tyrosine
      phosphatase from Yersinia. The K(i) for the d isomer is 33-fold lower than that
      of the l isomer, and is more than an order of magnitude lower than the reported
      K(m) of the substrate l-phosphotyrosine.

PMID- 15501072
TI  - 1,2,3,4-Tetrahydroquinoline-containing alphaVbeta3 integrin antagonists with
      enhanced oral bioavailability.
AB  - Reduction of the quinoline ring in an alpha(v)beta(3) antagonist yielded a
      1,2,3,4-tetrahydro derivative as two diastereomers, the four isomers of which
      were separated by sequential chiral HPLC. Two isomers had significant
      alpha(V)beta(3) antagonist activity with improved oral bioavailability, relative
      to the corresponding quinoline derivative.

PMID- 15501073
TI  - Unprecedented olefin-dependent histidine-kinase inhibitory of zerumbone ring
      opening material.
AB  - Zerumbone ring-opening derivative, 4 (10E/10Z=3/2), inhibited autophosphorylation
      of the essential histidine-kinase YycG existing in Bacillus subtilis constituting
      a two-component system (TCS). Generation of 4E-form could be regulated chemically
      using the difference from the ring-opening reactivity of the precursor forming of
      4 and pure 4E was isolated. The stereoisomer, 4E, showed main inhibition activity
      of autophosphorylation of YycG (IC(50)=63.5 microM).

PMID- 15501074
TI  - COX-2 inhibition as a tool to treat and prevent colorectal cancer.
AB  - The cyclooxygenase-2 (COX-2) enzyme has a fundamental role in the carcinogenesis
      of colorectal cancer. The anticarcinogenic mechanisms of NSAIDs are not
      completely understood and appear to be only partially dependent on inhibition
      tumoral COX-2. Moreover, the mechanisms of NSAIDs depend on the concentration. In
      experimental setting, at low levels NSAIDs downregulate the COX-2 gene in
      colorectal cancer cells, whereas at clinical relevant concentrations the
      production of prostaglandin E2 by enzymatic activity of COX-2 is diminished
      resulting in inhibition of the tumor angiogenesis. At higher levels NSAIDs and
      especially some selective COX-2 inhibitors are capable of COX-2 independent
      effects, such as apoptosis induction of tumor cells. In animal models, NSAIDs
      administration results in inhibition of angiogenesis and proliferation, induction
      apoptosis and prevention of metastasis. In clinical setting, NSAIDs and selective
      COX-2 inhibitors have the capacity to prevent the development of colorectal
      adenomas. We have summarized data regarding the role of COX-2 in CRC and discuss
      the multiple targets of NSAIDs in their anticarcinogenic action. However, the
      translation of these anticarcinogenic effects of NSAIDs to its clinical
      application as adjuvant therapy in CRC is hampered by a lack of randomized
      clinical trials with long-term follow-up.

PMID- 15501075
TI  - Mutational spectrum of p53 mutations in primary breast and ovarian tumors.
AB  - Breast and ovarian cancers, like other cancers, occur due to genetic damage.
      Research aimed to determine the specific genes involved in the development of
      breast and ovarian cancers will help to understand how normal breast and ovarian
      epithelial cells escape regulation of proliferation, apoptosis and senescence. It
      was determined that approximately 10% of ovarian cancers and 20-30% of breast
      cancers arise in women who have inherited mutations in cancer susceptibility
      genes such as BRCA1, BRCA2 and other DNA repair genes. The ability to perform
      genetic testing permits the identification of women at increased risk who can
      then be offered preventive strategies. The vast majority of ovarian and breast
      cancers are sporadic, presumably resulting from the accumulation of genetic
      damage over lifetime. Several genes involved in breast and ovarian carcinogenesis
      have been identified, most notably the p53 tumor suppressor. The recent
      availability of expression microarrays has facilitated the simultaneous screening
      of thousands of genes and this will extend further the understanding of molecular
      events involved in the dynamic development of ovarian and breast cancers. Then,
      all this knowledge could be translated into effective screening, surveillance,
      prevention, and treatment strategies in the future.

PMID- 15501076
TI  - Treatment of small cell lung cancer.
AB  - The incidence of small cell lung cancer (SCLC) is declining in the United States
      (US). SCLC is nearly universally smoking-related and is very sensitive to both
      chemotherapy and radiation therapy. In contrast to non-small cell lung cancer
      (NSCLC), SCLC is staged as either limited-stage disease (LD) or extensive-stage
      disease (ED). Chemotherapy remains the essential component for treatment of all
      patients with SCLC, regardless of stage or performance status. In LD, the
      addition of radiation therapy improves survival over chemotherapy alone. However,
      the dose, timing and schedule of radiation are not well defined. Prophylactic
      cranial irradiation (PCI) reduces brain relapse rates, and modestly improves
      survival in patients in a clinical remission. Many chemotherapy agents and
      combinations result in high response rates in ED SCLC; however, median survival
      time remains 8-10 months. Cisplatin (or carboplatin) and etoposide is the
      standard doublet used in the United States. One study has shown cisplatin plus
      irinotecan to have a survival benefit over cisplatin plus etoposide, but
      confirmatory studies are needed. Patients with ED frequently relapse, and
      relapsed/refractory SCLC has a poor prognosis. The challenge remains to identify
      novel therapies and molecular targets to improve survival in SCLC.

PMID- 15501077
TI  - Statements on the interdependence between the oncologist and the geriatrician in
      geriatric oncology.
AB  - Geriatric oncology is defined by the multidimensional and multidisciplinary
      approach of the elderly cancer patients. Autonomy, beneficence, non-maleficence
      and justice are the four fundamental principles on which are based the treatment
      objectives and practical management of these patients. The comprehensive
      geriatric assessment is the tool the most likely to detect the functional
      problems in these elderly patients. The standard oncologic managements of cancer
      are applicable to these patients. However treatment plan and geriatric
      interventions must be tailored to each individual patient characteristics. Thus a
      strong interdependence between oncologic and geriatric teams is warranted. This
      implies specific teaching programs during initial medical studies and in the
      setting of continuous medical education. Furthermore, such worldwide teaching
      programs may help to the implementation of geriatric oncology programs which is
      only based, to date, on personal experiences as described in this report.

PMID- 15501078
TI  - How do we manage breast cancer in the elderly patients? A survey among members of
      the British Association of Surgical Oncologists (BASO).
AB  - AIMS: To frame the attitude and perception of breast surgeons in the UK toward
      the increasing number of older breast cancer patients. METHODS: A 15-item
      questionnaire was designed to inquire on the definition of elderly, clinical
      management, age-related differences in surgical treatment, interaction with
      geriatricians, operative risk assessment, and surveyed identification/descriptive
      data. The questionnaire was sent to all 350 ABS associates (Association of Breast
      Surgery) at the British Association of Surgical Oncology (BASO). RESULTS: A 150
      questionnaires were returned (compliance 43%) providing the largest sample of
      breast surgical specialist overview on this topic. The major part of the surveyed
      (44%) stated age does not stand as the most relevant factor on its own in
      identifying a patient as "elderly", nor in offering surgical management (98%) and
      in dealing with the axilla (75%). The surveyed are aware of the burden of this
      epidemiological problem and would rather finalise the decision-making process
      based on multiple factors. This is to tailor the most appropriate treatment
      aiming to improving quality of life (42%) and quality adjusted survival (40%).
      Although most breast surgeons are inclined to discuss their onco-geriatric
      patients with geriatricians on a regular (32%) or occasional (42%) basis, no
      geriatric assessment is routinely utilised (82%) and the operative risk is
      predicted with ASA (45%). These figures confirm the surveyed breast surgeons in
      the UK are not biased by an ageistic approach, and aim to achieve a global well
      being to the older patients with breast cancer. CONCLUSIONS: This survey confirms
      our lack of knowledge in the management of elderly patients affected by breast
      cancer. Taken into account the limitations of a survey, we are pleased to confirm
      the performance of the largest part of breast surgeons at BASO is not biased by
      an ageist mentality.

PMID- 15501080
TI  - Cortical surface segmentation and mapping.
AB  - Segmentation and mapping of the human cerebral cortex from magnetic resonance
      (MR) images plays an important role in neuroscience and medicine. This paper
      describes a comprehensive approach for cortical reconstruction, flattening, and
      sulcal segmentation. Robustness to imaging artifacts and anatomical consistency
      are key achievements in an overall approach that is nearly fully automatic and
      computationally fast. Results demonstrating the application of this approach to a
      study of cortical thickness changes in aging are presented.

PMID- 15501081
TI  - Cortical cartography using the discrete conformal approach of circle packings.
AB  - Cortical flattening algorithms are becoming more widely used to assist in
      visualizing the convoluted cortical gray matter sheet of the brain. Metric-based
      approaches are the most common but suffer from high distortions. Conformal, or
      angle-based algorithms, are supported by a comprehensive mathematical theory. The
      conformal approach that uses circle packings is versatile in the manipulation and
      display of results. In addition, it offers some new and interesting metrics that
      may be useful in neuroscientific analysis and are not available through numerical
      partial differential equation conformal methods. In this paper, we begin with a
      brief description of cortical "flat" mapping, from data acquisition to map
      displays, including a brief review of past flat mapping approaches. We then
      describe the mathematics of conformal geometry and key elements of conformal
      mapping. We introduce the mechanics of circle packing and discuss its connections
      with conformal geometry. Using a triangulated surface representing a cortical
      hemisphere, we illustrate several manipulations available using circle packing
      methods and describe the associated "ensemble conformal features" (ECFs). We
      conclude by discussing current and potential uses of conformal methods in
      neuroscience and computational anatomy.

PMID- 15501082
TI  - A framework to study the cortical folding patterns.
AB  - This paper describes a decade-long research program focused on the variability of
      the cortical folding patterns. The program has developed a framework of using
      artificial neuroanatomists that are trained to identify sulci from a database.
      The framework relies on a renormalization of the brain warping problem, which
      consists in matching the cortices at the scale of the folds. Another component of
      the program is the search for the alphabet of the folding patterns, namely, a
      list of indivisible elementary sulci. The search relies on the study of the
      cortical folding process using antenatal imaging and on backward simulations of
      morphogenesis aimed at revealing traces of the embryologic dimples in the mature
      cortical surface. The importance of sulcal-based morphometry is illustrated by a
      simple study of the correlates of handedness on asymmetry indices. The study
      shows for instance that the central sulcus is larger in the dominant hemisphere.

PMID- 15501083
TI  - Geodesic estimation for large deformation anatomical shape averaging and
      interpolation.
AB  - The goal of this research is to promote variational methods for anatomical
      averaging that operate within the space of the underlying image registration
      problem. This approach is effective when using the large deformation viscous
      framework, where linear averaging is not valid, or in the elastic case. The
      theory behind this novel atlas building algorithm is similar to the traditional
      pairwise registration problem, but with single image forces replaced by average
      forces. These group forces drive an average transport ordinary differential
      equation allowing one to estimate the geodesic that moves an image toward the
      mean shape configuration. This model gives large deformation atlases that are
      optimal with respect to the shape manifold as defined by the data and the image
      registration assumptions. We use the techniques in the large deformation context
      here, but they also pertain to small deformation atlas construction. Furthermore,
      a natural, inherently inverse consistent image registration is gained for free,
      as is a tool for constant arc length geodesic shape interpolation. The geodesic
      atlas creation algorithm is quantitatively compared to the Euclidean anatomical
      average to elucidate the need for optimized atlases. The procedures generate
      improved average representations of highly variable anatomy from distinct
      populations.

PMID- 15501084
TI  - Unbiased diffeomorphic atlas construction for computational anatomy.
AB  - Construction of population atlases is a key issue in medical image analysis, and
      particularly in brain mapping. Large sets of images are mapped into a common
      coordinate system to study intra-population variability and inter-population
      differences, to provide voxel-wise mapping of functional sites, and help tissue
      and object segmentation via registration of anatomical labels. Common techniques
      often include the choice of a template image, which inherently introduces a bias.
      This paper describes a new method for unbiased construction of atlases in the
      large deformation diffeomorphic setting. A child neuroimaging autism study serves
      as a driving application. There is lack of normative data that explains average
      brain shape and variability at this early stage of development. We present work
      in progress toward constructing an unbiased MRI atlas of 2 years of children and
      the building of a probabilistic atlas of anatomical structures, here the caudate
      nucleus. Further, we demonstrate the segmentation of new subjects via atlas
      mapping. Validation of the methodology is performed by comparing the deformed
      probabilistic atlas with existing manual segmentations.

PMID- 15501085
TI  - Statistics on diffeomorphisms via tangent space representations.
AB  - In this paper, we present a linear setting for statistical analysis of shape and
      an optimization approach based on a recent derivation of a conservation of
      momentum law for the geodesics of diffeomorphic flow. Once a template is fixed,
      the space of initial momentum becomes an appropriate space for studying shape via
      geodesic flow since the flow at any point along the geodesic is completely
      determined by the momentum at the origin through geodesic shooting equations. The
      space of initial momentum provides a linear representation of the nonlinear
      diffeomorphic shape space in which linear statistical analysis can be applied.
      Specializing to the landmark matching problem of Computational Anatomy, we derive
      an algorithm for solving the variational problem with respect to the initial
      momentum and demonstrate principal component analysis (PCA) in this setting with
      three-dimensional face and hippocampus databases.

PMID- 15501086
TI  - Soliton dynamics in computational anatomy.
AB  - Computational anatomy (CA) has introduced the idea of anatomical structures being
      transformed by geodesic deformations on groups of diffeomorphisms. Among these
      geometric structures, landmarks and image outlines in CA are shown to be singular
      solutions of a partial differential equation that is called the geodesic EPDiff
      equation. A recently discovered momentum map for singular solutions of EPDiff
      yields their canonical Hamiltonian formulation, which in turn provides a complete
      parameterization of the landmarks by their canonical positions and momenta. The
      momentum map provides an isomorphism between landmarks (and outlines) for images
      and singular soliton solutions of the EPDiff equation. This isomorphism suggests
      a new dynamical paradigm for CA, as well as new data representation.

PMID- 15501087
TI  - Implicit brain imaging.
AB  - We describe how implicit surface representations can be used to solve fundamental
      problems in brain imaging. This kind of representation is not only natural
      following the state-of-the-art segmentation algorithms reported in the literature
      to extract the different brain tissues, but it is also, as shown in this paper,
      the most appropriate one from the computational point of view. Examples are
      provided for finding constrained special curves on the cortex, such as sulcal
      beds, regularizing surface-based measures, such as cortical thickness, and for
      computing warping fields between surfaces such as the brain cortex. All these
      result from efficiently solving partial differential equations (PDEs) and
      variational problems on surfaces represented in implicit form. The implicit
      framework avoids the need to construct intermediate mappings between 3-D
      anatomical surfaces and parametric objects such planes or spheres, a complex step
      that introduces errors and is required by many other cortical processing
      approaches.

PMID- 15501088
TI  - Unified univariate and multivariate random field theory.
AB  - We report new random field theory P values for peaks of canonical correlation
      SPMs for detecting multiple contrasts in a linear model for multivariate image
      data. This completes results for all types of univariate and multivariate image
      data analysis. All other known univariate and multivariate random field theory
      results are now special cases, so these new results present a true unification of
      all currently known results. As an illustration, we use these results in a
      deformation-based morphometry (DBM) analysis to look for regions of the brain
      where vector deformations of nonmissile trauma patients are related to several
      verbal memory scores, to detect regions of changes in anatomical effective
      connectivity between the trauma patients and a group of age- and sex-matched
      controls, and to look for anatomical connectivity in cortical thickness.

PMID- 15501089
TI  - Computational anatomy: shape, growth, and atrophy comparison via diffeomorphisms.
AB  - Computational anatomy (CA) is the mathematical study of anatomy I in I = I(alpha)
      o G, an orbit under groups of diffeomorphisms (i.e., smooth invertible mappings)
      g in G of anatomical exemplars I(alpha) in I. The observable images are the
      output of medical imaging devices. There are three components that CA examines:
      (i) constructions of the anatomical submanifolds, (ii) comparison of the
      anatomical manifolds via estimation of the underlying diffeomorphisms g in G
      defining the shape or geometry of the anatomical manifolds, and (iii) generation
      of probability laws of anatomical variation P(.) on the images I for inference
      and disease testing within anatomical models. This paper reviews recent advances
      in these three areas applied to shape, growth, and atrophy.

PMID- 15501090
TI  - Optimizing the fMRI data-processing pipeline using prediction and reproducibility
      performance metrics: I. A preliminary group analysis.
AB  - We argue that published results demonstrate that new insights into human brain
      function may be obscured by poor and/or limited choices in the data-processing
      pipeline, and review the work on performance metrics for optimizing pipelines:
      prediction, reproducibility, and related empirical Receiver Operating
      Characteristic (ROC) curve metrics. Using the NPAIRS split-half resampling
      framework for estimating prediction/reproducibility metrics (Strother et al.,
      2002), we illustrate its use by testing the relative importance of selected
      pipeline components (interpolation, in-plane spatial smoothing, temporal
      detrending, and between-subject alignment) in a group analysis of BOLD-fMRI scans
      from 16 subjects performing a block-design, parametric-static-force task. Large
      scale brain networks were detected using a multivariate linear discriminant
      analysis (canonical variates analysis, CVA) that was tuned to fit the data. We
      found that tuning the CVA model and spatial smoothing were the most important
      processing parameters. Temporal detrending was essential to remove low-frequency,
      reproducing time trends; the number of cosine basis functions for detrending was
      optimized by assuming that separate epochs of baseline scans have constant, equal
      means, and this assumption was assessed with prediction metrics. Higher-order
      polynomial warps compared to affine alignment had only a minor impact on the
      performance metrics. We found that both prediction and reproducibility metrics
      were required for optimizing the pipeline and give somewhat different results.
      Moreover, the parameter settings of components in the pipeline interact so that
      the current practice of reporting the optimization of components tested in
      relative isolation is unlikely to lead to fully optimized processing pipelines.

PMID- 15501091
TI  - Mapping cortical change in Alzheimer's disease, brain development, and
      schizophrenia.
AB  - This paper describes algorithms that can identify patterns of brain structure and
      function associated with Alzheimer's disease, schizophrenia, normal aging, and
      abnormal brain development based on imaging data collected in large human
      populations. Extraordinary information can be discovered with these techniques:
      dynamic brain maps reveal how the brain grows in childhood, how it changes in
      disease, and how it responds to medication. Genetic brain maps can reveal genetic
      influences on brain structure, shedding light on the nature-nurture debate, and
      the mechanisms underlying inherited neurobehavioral disorders. Recently, we
      created time-lapse movies of brain structure for a variety of diseases. These
      identify complex, shifting patterns of brain structural deficits, revealing
      where, and at what rate, the path of brain deterioration in illness deviates from
      normal. Statistical criteria can then identify situations in which these changes
      are abnormally accelerated, or when medication or other interventions slow them.
      In this paper, we focus on describing our approaches to map structural changes in
      the cortex. These methods have already been used to reveal the profile of brain
      anomalies in studies of dementia, epilepsy, depression, childhood- and adult
      onset schizophrenia, bipolar disorder, attention-deficit/hyperactivity disorder,
      fetal alcohol syndrome, Tourette syndrome, Williams syndrome, and in
      methamphetamine abusers. Specifically, we describe an image analysis pipeline
      known as cortical pattern matching that helps compare and pool cortical data over
      time and across subjects. Statistics are then defined to identify brain
      structural differences between groups, including localized alterations in
      cortical thickness, gray matter density (GMD), and asymmetries in cortical
      organization. Subtle features, not seen in individual brain scans, often emerge
      when population-based brain data are averaged in this way. Illustrative examples
      are presented to show the profound effects of development and various diseases on
      the human cortex. Dynamically spreading waves of gray matter loss are tracked in
      dementia and schizophrenia, and these sequences are related to normally occurring
      changes in healthy subjects of various ages.

PMID- 15501092
TI  - Advances in functional and structural MR image analysis and implementation as
      FSL.
AB  - The techniques available for the interrogation and analysis of neuroimaging data
      have a large influence in determining the flexibility, sensitivity, and scope of
      neuroimaging experiments. The development of such methodologies has allowed
      investigators to address scientific questions that could not previously be
      answered and, as such, has become an important research area in its own right. In
      this paper, we present a review of the research carried out by the Analysis Group
      at the Oxford Centre for Functional MRI of the Brain (FMRIB). This research has
      focussed on the development of new methodologies for the analysis of both
      structural and functional magnetic resonance imaging data. The majority of the
      research laid out in this paper has been implemented as freely available software
      tools within FMRIB's Software Library (FSL).

PMID- 15501093
TI  - Modeling the hemodynamic response to brain activation.
AB  - Neural activity in the brain is accompanied by changes in cerebral blood flow
      (CBF) and blood oxygenation that are detectable with functional magnetic
      resonance imaging (fMRI) techniques. In this paper, recent mathematical models of
      this hemodynamic response are reviewed and integrated. Models are described for:
      (1) the blood oxygenation level dependent (BOLD) signal as a function of changes
      in cerebral oxygen extraction fraction (E) and cerebral blood volume (CBV); (2)
      the balloon model, proposed to describe the transient dynamics of CBV and deoxy
      hemoglobin (Hb) and how they affect the BOLD signal; (3) neurovascular coupling,
      relating the responses in CBF and cerebral metabolic rate of oxygen (CMRO(2)) to
      the neural activity response; and (4) a simple model for the temporal
      nonlinearity of the neural response itself. These models are integrated into a
      mathematical framework describing the steps linking a stimulus to the measured
      BOLD and CBF responses. Experimental results examining transient features of the
      BOLD response (post-stimulus undershoot and initial dip), nonlinearities of the
      hemodynamic response, and the role of the physiologic baseline state in altering
      the BOLD signal are discussed in the context of the proposed models. Quantitative
      modeling of the hemodynamic response, when combined with experimental data
      measuring both the BOLD and CBF responses, makes possible a more specific and
      quantitative assessment of brain physiology than is possible with standard BOLD
      imaging alone. This approach has the potential to enhance numerous studies of
      brain function in development, health, and disease.

PMID- 15501094
TI  - Wavelets and functional magnetic resonance imaging of the human brain.
AB  - The discrete wavelet transform (DWT) is widely used for multiresolution analysis
      and decorrelation or "whitening" of nonstationary time series and spatial
      processes. Wavelets are naturally appropriate for analysis of biological data,
      such as functional magnetic resonance images of the human brain, which often
      demonstrate scale invariant or fractal properties. We provide a brief formal
      introduction to key properties of the DWT and review the growing literature on
      its application to fMRI. We focus on three applications in particular: (i)
      wavelet coefficient resampling or "wavestrapping" of 1-D time series, 2- to 3-D
      spatial maps and 4-D spatiotemporal processes; (ii) wavelet-based estimators for
      signal and noise parameters of time series regression models assuming the errors
      are fractional Gaussian noise (fGn); and (iii) wavelet shrinkage in frequentist
      and Bayesian frameworks to support multiresolution hypothesis testing on
      spatially extended statistic maps. We conclude that the wavelet domain is a rich
      source of new concepts and techniques to enhance the power of statistical
      analysis of human fMRI data.

PMID- 15501095
TI  - Partial least squares analysis of neuroimaging data: applications and advances.
AB  - Partial least squares (PLS) analysis has been used to characterize distributed
      signals measured by neuroimaging methods like positron emission tomography (PET),
      functional magnetic resonance imaging (fMRI), event-related potentials (ERP) and
      magnetoencephalography (MEG). In the application to PET, it has been used to
      extract activity patterns differentiating cognitive tasks, patterns relating
      distributed activity to behavior, and to describe large-scale interregional
      interactions or functional connections. This paper reviews the more recent
      extension of PLS to the analysis of spatiotemporal patterns present in fMRI, ERP,
      and MEG data. We present a basic mathematical description of PLS and discuss the
      statistical assessment using permutation testing and bootstrap resampling. These
      two resampling methods provide complementary information of the statistical
      strength of the extracted activity patterns (permutation test) and the
      reliability of regional contributions to the patterns (bootstrap resampling).
      Simulated ERP data are used to guide the basic interpretation of spatiotemporal
      PLS results, and examples from empirical ERP and fMRI data sets are used for
      further illustration. We conclude with a discussion of some caveats in the use of
      PLS, including nonlinearities, nonorthogonality, and interpretation difficulties.
      We further discuss its role as an important tool in a pluralistic analytic
      approach to neuroimaging.

PMID- 15501096
TI  - Modelling functional integration: a comparison of structural equation and dynamic
      causal models.
AB  - The brain appears to adhere to two fundamental principles of functional
      organisation, functional integration and functional specialisation, where the
      integration within and among specialised areas is mediated by effective
      connectivity. In this paper, we review two different approaches to modelling
      effective connectivity from fMRI data, structural equation models (SEMs) and
      dynamic causal models (DCMs). In common to both approaches are model comparison
      frameworks in which inferences can be made about effective connectivity per se
      and about how that connectivity can be changed by perceptual or cognitive set.
      Underlying the two approaches, however, are two very different generative models.
      In DCM, a distinction is made between the 'neuronal level' and the 'hemodynamic
      level'. Experimental inputs cause changes in effective connectivity expressed at
      the level of neurodynamics, which in turn cause changes in the observed
      hemodynamics. In SEM, changes in effective connectivity lead directly to changes
      in the covariance structure of the observed hemodynamics. Because changes in
      effective connectivity in the brain occur at a neuronal level DCM is the
      preferred model for fMRI data. This review focuses on the underlying assumptions
      and limitations of each model and demonstrates their application to data from a
      study of attention to visual motion.

PMID- 15501097
TI  - Diffuse optical imaging of brain activation: approaches to optimizing image
      sensitivity, resolution, and accuracy.
AB  - Near-infrared spectroscopy (NIRS) and diffuse optical imaging (DOI) are finding
      widespread application in the study of human brain activation, motivating further
      application-specific development of the technology. NIRS and DOI offer the
      potential to quantify changes in deoxyhemoglobin (HbR) and total hemoglobin (HbT)
      concentration, thus enabling distinction of oxygen consumption and blood flow
      changes during brain activation. While the techniques implemented presently
      provide important results for cognition and the neurosciences through their
      relative measures of HbR and HbT concentrations, there is much to be done to
      improve sensitivity, accuracy, and resolution. In this paper, we review the
      advances currently being made and issues to consider for improving optical image
      quality. These include the optimal selection of wavelengths to minimize random
      and systematic error propagation in the calculation of the hemoglobin
      concentrations, the filtering of systemic physiological signal clutter to improve
      sensitivity to the hemodynamic response to brain activation, the implementation
      of overlapping measurements to improve image spatial resolution and uniformity,
      and the utilization of spatial prior information from structural and functional
      MRI to reduce DOI partial volume error and improve image quantitative accuracy.

PMID- 15501098
TI  - Mapping human brain function with MEG and EEG: methods and validation.
AB  - We survey the field of magnetoencephalography (MEG) and electroencephalography
      (EEG) source estimation. These modalities offer the potential for functional
      brain mapping with temporal resolution in the millisecond range. However, the
      limited number of spatial measurements and the ill-posedness of the inverse
      problem present significant limits to our ability to produce accurate spatial
      maps from these data without imposing major restrictions on the form of the
      inverse solution. Here we describe approaches to solving the forward problem of
      computing the mapping from putative inverse solutions into the data space. We
      then describe the inverse problem in terms of low dimensional solutions, based on
      the equivalent current dipole (ECD), and high dimensional solutions, in which
      images of neural activation are constrained to the cerebral cortex. We also
      address the issue of objective assessment of the relative performance of inverse
      procedures by the free-response receiver operating characteristic (FROC) curve.
      We conclude with a discussion of methods for assessing statistical significance
      of experimental results through use of the bootstrap for determining confidence
      regions in dipole-fitting methods, and random field (RF) and permutation methods
      for detecting significant activation in cortically constrained imaging studies.

PMID- 15501099
TI  - Geometric strategies for neuroanatomic analysis from MRI.
AB  - In this paper, we describe ongoing work in the Image Processing and Analysis
      Group (IPAG) at Yale University specifically aimed at the analysis of structural
      information as represented within magnetic resonance images (MRI) of the human
      brain. Specifically, we will describe our applied mathematical approaches to the
      segmentation of cortical and subcortical structure, the analysis of white matter
      fiber tracks using diffusion tensor imaging (DTI), and the intersubject
      registration of neuroanatomical (aMRI) data sets. Many of our methods rally
      around the use of geometric constraints, statistical (MAP) estimation, and the
      use of level set evolution strategies. The analysis of gray matter structure and
      connecting white matter paths combined with the ability to bring all information
      into a common space via intersubject registration should provide us with a rich
      set of data to investigate structure and variation in the human brain in
      neuropsychiatric disorders, as well as provide a basis for current work in the
      development of integrated brain function-structure analysis.

PMID- 15501100
TI  - Variational, geometric, and statistical methods for modeling brain anatomy and
      function.
AB  - We survey the recent activities of the Odyssee Laboratory in the area of the
      application of mathematics to the design of models for studying brain anatomy and
      function. We start with the problem of reconstructing sources in MEG and EEG, and
      discuss the variational approach we have developed for solving these inverse
      problems. This motivates the need for geometric models of the head. We present a
      method for automatically and accurately extracting surface meshes of several
      tissues of the head from anatomical magnetic resonance (MR) images. Anatomical
      connectivity can be extracted from diffusion tensor magnetic resonance images
      but, in the current state of the technology, it must be preceded by a robust
      estimation and regularization stage. We discuss our work based on variational
      principles and show how the results can be used to track fibers in the white
      matter (WM) as geodesics in some Riemannian space. We then go to the statistical
      modeling of functional magnetic resonance imaging (fMRI) signals from the
      viewpoint of their decomposition in a pseudo-deterministic and stochastic part
      that we then use to perform clustering of voxels in a way that is inspired by the
      theory of support vector machines and in a way that is grounded in information
      theory. Multimodal image matching is discussed next in the framework of image
      statistics and partial differential equations (PDEs) with an eye on registering
      fMRI to the anatomy. The paper ends with a discussion of a new theory of random
      shapes that may prove useful in building anatomical and functional atlases.

PMID- 15501101
TI  - Computational anatomy and neuropsychiatric disease: probabilistic assessment of
      variation and statistical inference of group difference, hemispheric asymmetry,
      and time-dependent change.
AB  - Three components of computational anatomy (CA) are reviewed in this paper: (i)
      the computation of large-deformation maps, that is, for any given coordinate
      system representations of two anatomies, computing the diffeomorphic
      transformation from one to the other; (ii) the computation of empirical
      probability laws of anatomical variation between anatomies; and (iii) the
      construction of inferences regarding neuropsychiatric disease states. CA utilizes
      spatial-temporal vector field information obtained from large-deformation maps to
      assess anatomical variabilities and facilitate the detection and quantification
      of abnormalities of brain structure in subjects with neuropsychiatric disorders.
      Neuroanatomical structures are divided into two types: subcortical structures
      gray matter (GM) volumes enclosed by a single surface-and cortical mantle
      structures-anatomically distinct portions of the cerebral cortical mantle layered
      between the white matter (WM) and cerebrospinal fluid (CSF). Because of
      fundamental differences in the geometry of these two types of structures, image
      based large-deformation high-dimensional brain mapping (HDBM-LD) and large
      deformation diffeomorphic metric matching (LDDMM) were developed for the study of
      subcortical structures and labeled cortical mantle distance mapping (LCMDM) was
      developed for the study of cortical mantle structures. Studies of
      neuropsychiatric disorders using CA usually require the testing of hypothesized
      group differences with relatively small numbers of subjects per group. Approaches
      that increase the power for testing such hypotheses include methods to quantify
      the shapes of individual structures, relationships between the shapes of related
      structures (e.g., asymmetry), and changes of shapes over time. Promising
      preliminary studies employing these approaches to studies of subjects with
      schizophrenia and very mild to mild Alzheimer's disease (AD) are presented.

PMID- 15501102
TI  - Sequence-independent segmentation of magnetic resonance images.
AB  - We present a set of techniques for embedding the physics of the imaging process
      that generates a class of magnetic resonance images (MRIs) into a segmentation or
      registration algorithm. This results in substantial invariance to acquisition
      parameters, as the effect of these parameters on the contrast properties of
      various brain structures is explicitly modeled in the segmentation. In addition,
      the integration of image acquisition with tissue classification allows the
      derivation of sequences that are optimal for segmentation purposes. Another
      benefit of these procedures is the generation of probabilistic models of the
      intrinsic tissue parameters that cause MR contrast (e.g., T1, proton density,
      T2*), allowing access to these physiologically relevant parameters that may
      change with disease or demographic, resulting in nonmorphometric alterations in
      MR images that are otherwise difficult to detect. Finally, we also present a high
      band width multiecho FLASH pulse sequence that results in high signal-to-noise
      ratio with minimal image distortion due to B0 effects. This sequence has the
      added benefit of allowing the explicit estimation of T2* and of reducing test
      retest intensity variability.

PMID- 15501103
TI  - Expert knowledge-guided segmentation system for brain MRI.
AB  - We describe an automated 3-D segmentation system for in vivo brain magnetic
      resonance images (MRI). Our segmentation method combines a variety of filtering,
      segmentation, and registration techniques and makes maximum use of the available
      a priori biomedical expertise, both in an implicit and an explicit form. We
      approach the issue of boundary finding as a process of fitting a group of
      deformable templates (simplex mesh surfaces) to the contours of the target
      structures. These templates evolve in parallel, supervised by a series of rules
      derived from analyzing the template's dynamics and from medical experience. The
      templates are also constrained by knowledge on the expected textural and shape
      properties of the target structures. We apply our system to segment four brain
      structures (corpus callosum, ventricles, hippocampus, and caudate nuclei) and
      discuss its robustness to imaging characteristics and acquisition noise.

PMID- 15501104
TI  - Surface-based approaches to spatial localization and registration in primate
      cerebral cortex.
AB  - Explicit surface reconstructions provide invaluable substrates for visualizing
      and analyzing the complex convolutions of cerebral cortex. This report
      illustrates the utility of surface-based atlases of human and macaque monkey for
      representing many aspects of cortical organization and function. These include a
      variety of cortical partitioning schemes plus an open-ended collection of complex
      activation patterns obtained from fMRI studies. Surface-based registration from
      one hemisphere to an atlas provides powerful approach to (i) objectively and
      quantitatively representing both the consistencies and the variability of the
      pattern of convolutions and the patterns of functional activation from any given
      task; and (ii) making comparisons across species and evaluating candidate
      homologies between cortical areas or functionally delineated regions.

PMID- 15501105
TI  - Standardized approach to laparoscopic right colectomy: outcomes in 70 consecutive
      cases.
AB  - BACKGROUND: The purpose of this article is to describe a standard operative
      technique, postoperative care plan, and outcomes for laparoscopic right
      hemicolectomy. STUDY DESIGN: A consecutive series of patients requiring
      laparoscopic right colectomy for neoplasia from March 1999 to April 2003 at the
      Cleveland Clinic Foundation, Cleveland, OH, were analyzed. Data collected
      included age, gender, indication for surgery, American Society of Anesthesiology
      class, body-mass index, operative duration, length of hospital stay,
      complications, mortality, and 30-day readmission rate. Operative steps and
      instrumentation for the procedure were standardized. Conversion was performed
      when a sequential step could not be completed in a reasonable time frame. A
      standard perioperative care plan was used. RESULTS: From March 1999 through April
      2003, 70 laparoscopic right hemicolectomies were attempted and 64 (90.1%) were
      completed. Indications for resection were cancer (30) and polyps (38). The mean
      operative time was 85 +/- 32 minutes. Mean length of hospital stay was 3.2 +/- 2
      days for completed cases and 4.3 +/- 2 days for converted cases. Anastomotic
      leaks occurred in 2 (2.8%) patients. The morbidity rate including the anastomotic
      leaks was 7.1%. There were no operative mortalities or port site tumor
      recurrences. CONCLUSIONS: Results indicate that a structured approach to
      laparoscopic right colectomy is associated with reasonable operative times,
      acceptable morbidity, and reductions in hospital stay.

PMID- 15501106
TI  - What pathologic features influence survival in patients with local residual tumor
      after resection of colorectal cancer?
AB  - BACKGROUND: Local residual tumor predicts poor patient survival after resection
      for colorectal cancer. The aim of this study was to determine the prevalence of
      residual tumor in a line of resection in a large prospective series and to
      identify other pathology variables that may influence survival in the absence of
      distant metastases in such patients. STUDY DESIGN: This study was based on all
      patients who had a resection for colorectal cancer at Concord Hospital between
      1971 and 2001. Patients were followed up annually until death or December 2002.
      Survival analysis used the Kaplan-Meier method and log rank test. Proportional
      hazards regression was used in multivariate modeling. RESULTS: The overall
      prevalence of residual tumor in a line of resection was 5.9%. Of 12 pathology
      variables examined, only high grade and apical node metastasis were independently
      associated with survival in the subset of 120 patients with residual tumor in a
      line of resection but without distant metastases. The 2-year survival rate for
      patients with neither of these adverse features was 46.4% (95% CI, 31.7% to
      59.9%) as compared with only 7.7% (CI, 0.5% to 29.2%) in those who had both.
      CONCLUSIONS: These results show that presence of local residual tumor after
      colorectal cancer resection does not carry a universally poor prognosis. Two
      specific histopathologic features independently associated with diminished
      survival were identified.

PMID- 15501107
TI  - Alcohol and illicit drugs in traumatic deaths: prevalence and association with
      type and severity of injuries.
AB  - BACKGROUND: My colleagues and I studied alcohol and illicit drug intoxication in
      trauma fatalities and their association with the nature and severity of injuries.
      STUDY DESIGN: We examined the trauma registry and autopsies of all trauma
      fatalities at an academic Level I trauma center. Statistical analysis was
      performed to evaluate the association of substance use with the Injury Severity
      Score, body areas with severe trauma (Abbreviated Injury Score >/= 3), and spinal
      injuries. RESULTS: From January 2000 to May 2003, 931 trauma deaths occurred; 600
      victims were tested for alcohol and illicit drugs and 256 of these (42.7%) tested
      positive. Male victims were significantly more likely to have a positive screen
      than female patients (46.1% versus 26.7%, p = 0.0003). Penetrating trauma was
      significantly more likely to be associated with a positive screen than blunt
      trauma (53.0% versus 31.0%, p < 0.001). Hispanic and African-American victims
      were more likely to have a positive screen than Caucasians or Asians. Half the
      patients in the age group 15 to 50 years had a positive screen. Victims with
      penetrating trauma and positive screen were significantly more likely to be dead
      at hospital arrival than victims with negative toxicology (68.8% versus 48.8%, p
      = 0.05). Pedestrians killed by automobiles who had positive screens were more
      likely to have severe abdominal trauma (Abbreviated Injury Score >/= 3) than
      victims with negative toxicology (54.2% versus 25.0%, p = 0.02). CONCLUSIONS:
      There is a high rate of alcohol and illicit drug use in patients who die from
      trauma, especially penetrating trauma in men aged 15 to 50 years, who are
      Hispanic or African American. Victims with penetrating trauma and positive
      toxicology are considerably more likely to have no vital signs on admission than
      victims with negative toxicology. Pedestrians killed by automobiles who had
      positive screens have a higher incidence of severe abdominal injuries than
      victims with negative screens.

PMID- 15501108
TI  - Resuscitation with a blood substitute causes vasoconstriction without nitric
      oxide scavenging in a model of arterial hemorrhage.
AB  - BACKGROUND: The purpose of this study was to determine if a hemoglobin-based
      oxygen carrier, HBOC-201 (Hemopure, Biopure Corp), alters endothelial function
      and nitric oxide physiology when used for hemorrhagic shock. STUDY DESIGN: Female
      swine (Sus scrofa) underwent catheterization of the femoral, circumflex iliac,
      and pulmonary arteries. Control animals (n = 3) underwent instrumentation only.
      Study animals underwent hemorrhage to mean arterial pressure of 30 +/- 5 mmHg,
      were maintained for 45 minutes, and resuscitated to the baseline mean arterial
      pressure for 4 hours. Resuscitation fluids included: shed blood (SB) (n = 8),
      lactated Ringers plus shed blood (LRSB) (n = 8), and HBOC (n = 8). At baseline,
      1, and 4 hours after resuscitation, acetylcholine was infused into the proximal
      iliac artery and endothelial-dependent relaxation was measured with M-mode
      ultrasonography. Nitric oxide levels were determined using a chemiluminescent
      assay. RESULTS: HBOC, SB, and LRSB provided equivalent survival and resuscitation
      as measured by mean arterial pressures (65.3 +/- 2.48 mmHg); pulmonary artery
      mean pressures (15.8 +/- 0.84 mmHg); and lactate levels (1.22 +/- 0.19 mmol/L).
      HBOC group animals required the lowest resuscitation volume (SB, 41.5 +/- 3.5
      mL/kg; LRSB, 76.4 +/- 1.1 mL/kg, HBOC, 14.6 +/- 2.1 mL/kg, p < 0.001). Response
      to acetylcholine was normal in the SB and LRSB groups, but the HBOC group had
      diminished acetylcholine response (29.5% endothelial-dependent relaxation end
      resuscitation, p < 0.001). Arterial nitric oxide levels did not differ between
      study groups (p = 0.69). CONCLUSIONS: HBOC might be an alternative resuscitation
      agent in patients with hemorrhagic shock. Resuscitation with HBOC requires less
      volume than blood or crystalloid. These data suggest HBOC-201 has a
      vasoconstrictive effect that cannot be attributed soley to nitric oxide
      scavenging.

PMID- 15501109
TI  - Major liver resection without clamping: a prospective reappraisal in the era of
      modern surgical tools.
AB  - BACKGROUND: Hemorrhage and transfusions remain the main causes of mortality and
      morbidity from liver resection. In cases of extended resection, especially
      performed on diseased liver, ischemia-reperfusion injury related to pedicle
      clamping may be a significant risk factor of postoperative liver dysfunction. The
      ideal alternative would be to perform major hepatectomy without clamping and
      without significant bleeding. STUDY DESIGN: This prospective study aimed to
      reconsider the risk of major hepatectomy performed without pedicle clamping and
      under low venous pressure in the light of modern surgical tools. Inclusion
      criteria were adults requiring a resection of more than three segments on healthy
      or pathologic livers but not on preoperative documented cirrhosis. RESULTS: Fifty
      patients, with a mean age of 53 +/- 15 years were included. Twenty-two patients
      had underlying liver disease. The main indications were colorectal metastases,
      primary liver tumors, and living donation. Twenty-six right hepatectomies, 17
      extended right hepatectomies, and 7 extended left hepatectomies were performed.
      Unclamping method was successful in 96% of patients on an intention-to-treat
      basis. Seventy-four percent of patients were not transfused and no patients died.
      Surgical complication rate was 16% but no complication led to reoperation.
      Medical complication rate was 20%, including three transient liver dysfunctions.
      CONCLUSIONS: Major hepatectomy without clamping can be performed safely. The low
      rate of postoperative liver dysfunction, especially in cases of underlying liver
      disease, suggests good preservation of the small and diseased remnant liver.

PMID- 15501110
TI  - Discontinuous, staccato growth of abdominal aortic aneurysms.
AB  - BACKGROUND: To evaluate whether abdominal aortic aneurysm (AAA) growth in
      individual patients can be characterized as continuous or discontinuous
      (staccato). STUDY DESIGN: From 1996 to 2002, 609 patients presented with
      unruptured AAAs. Of these, 278 underwent prompt repair and 331 were observed. In
      this study, we included 52 patients (16% of the latter group) who had at least
      four CT scans and were observed for 18 months or longer without any intervention.
      AAA growth was defined as any increase in diameter of >/= 3 mm over any
      observation period(s). AAA nongrowth was defined as absence of growth for at
      least 6 months. Staccato growth was defined as at least one period of nongrowth
      combined with at least one period of growth. RESULTS: The 52 patients had a mean
      age of 75 +/- 8 (SD) years. The mean observation period was 42 +/- 20 months and
      the mean AAA diameter growth rate was 3.6 +/- 2.4 mm/y. Only 12 of these 52
      patients (23%) demonstrated continuous growth. Staccato growth occurred in 34
      patients (65%). Six patients (12%) showed no growth at all over 18 to 57 months
      (mean 30 months). No correlation was observed between initial diameter of AAAs
      and a patient's individual growth rate during the whole observation period (R =
      0.04, p = 0.46). CONCLUSIONS: Individual AAA behavior is usually characterized by
      periods of nongrowth alternating with periods of growth, ie, staccato growth.
      Some aneurysms may have long periods of nongrowth. Accordingly, management
      decisions cannot be based on the presumption that observed growth rates of AAAs
      can be extrapolated to predict future growth rates.

PMID- 15501111
TI  - Effects of omega-3 fatty acid supplementation on tumor-bearing rats.
AB  - BACKGROUND: Dietary fish oil (rich in omega-3 fatty acids: eicosapentaenoic acid
      and docosahexaenoic acid) suppresses synthesis and activity of proinflammatory
      cytokines that induce anorexia. We hypothesized that dietary fish oil reverses
      the feeding pattern of tumor anorexia, increasing food intake and retarding tumor
      growth. STUDY DESIGN: Thirty-two Fischer rats were placed in Automated Eater
      Meter cages and randomly divided into four groups: tumor bearing (TB) rats eating
      normal chow diet (TB-Chow); TB rats eating chow diet supplemented with omega-3
      fatty acids (TB-omega-3FA); Controls, non-tumor bearing (NTB) rats eating normal
      chow (NTB-Chow); and NTB rats with omega-3 fatty acid supplementation (NTB-omega
      3FA). Doses of 10(6) methylcholanthrene (MCA) sarcoma cells were subcutaneously
      injected in TB rats. Daily food intake, meal size (MZ), meal number (MN), body
      weight, and tumor volume were measured, and rats were euthanized at onset of
      anorexia. Data were statistically analyzed using analyses of variance (ANOVA) and
      t-tests. Data are reported as mean +/- SE. RESULTS: Tumor appeared significantly
      earlier in TB-Chow than in TB-omega-3FA rats (7.5 +/- 0.3 days versus 11.6 +/-
      0.8 days, p < 0.05). Daily food intake declined significantly in TB-Chow versus
      TB-omega-3FA rats 18 days after tumor inoculation and, at onset of anorexia, was
      9.41 +/- 1.77 g/day versus 13.32 +/- 0.81 g/day, p < 0.05. Food intake decreased
      initially by decrease in meal number (at day 15) followed by a decrease in meal
      size (at day 18). At onset of anorexia, meal size and meal number were
      significantly decreased in TB-Chow versus TB-omega-3FA rats (0.75 +/- 0.067
      g/meal versus 1.05 +/- 0.08 g/meal, p < 0.05) and (9.5 +/- 1.32 versus 12.79 +/-
      0.93 meals/day, p < 0.05), respectively. Tumor volume was significantly smaller
      in TB-omega-3FA versus TB-Chow rats (7.6 +/- 0.6 cm(3) versus 16.5 +/- 1.0 cm(3),
      p < 0.05), as was tumor weight (7.5 +/- 2.2 g versus 18.1 +/- 1.6 g, p < 0.05).
      CONCLUSIONS: In TB rats, omega-3FA improved food intake; restored normal eating
      pattern, delayed onset of anorexia, tumor appearance, and growth; and prevented
      body weight loss. Supplementation of omega-3 fatty acids has therapeutic
      potential in cancer anorexia.

PMID- 15501112
TI  - Differential expression of the Tie-2 receptor and its ligands in human pancreatic
      tumors.
AB  - BACKGROUND: Derangements in the balance of the Tie-2 receptor ligands,
      angiopoietin-1 and angiopoietin-2 (Ang-1 and Ang-2), have been implicated in the
      growth and differentiation of several human tumors. To assess the potential role
      of angiogenesis factors in pancreatic tumorigenesis, we confirmed previously
      observed oligonucleotide-based microarray data by analyzing their expression in
      pancreatic tumors using semiquantitative reverse transcription polymerase chain
      reaction and immunohistochemistry. STUDY DESIGN: RNA harvested from tissue
      samples obtained from patients with normal pancreata, adenocarcinoma of the
      pancreas, and neuroendocrine tumors of the pancreas (nine each) was grouped by
      tissue type, pooled, and hybridized to a cDNA microarray and global gene
      expression patterns were determined. Semiquantitative reverse transcription
      polymerase chain reaction was applied to individual pool components to
      specifically determine expression of Tie-2, Ang-1, and Ang-2. A separate set of
      tumors and matched normal pancreas were then stained for expression of Ang-2
      protein using immunohistochemistry. RESULTS: Microarray data showed that Ang-2
      was upregulated in neuroendocrine tumors ( approximately 8 times more than
      normal) and adenocarcinoma of the pancreas ( approximately 5 times more than
      normal) although Ang-1 and Tie-2 were not differentially expressed. Reverse
      transcription polymerase chain reaction confirmed these findings showing strong
      Ang-2 expression in nine of nine neuroendocrine tumors, eight of nine
      adenocarcinoma of the pancreas, and weak expression in two of nine normal
      pancreata. Immunohistochemistry showed tumor-specific staining of Ang-2 in 10 of
      15 matched adenocarcinoma of the pancreas (67%) and 6 of 8 neuroendocrine tumors
      (75%). CONCLUSIONS: Although Tie-2 and Ang-1 are not differentially expressed in
      pancreatic tumors, Ang-2 gene and gene product are overexpressed, suggesting a
      significant role for Ang-2 in pancreatic tumorigenesis. Differential expression
      of Ang-2 in human tumors may be useful as a diagnostic and therapeutic target.

PMID- 15501113
TI  - Accountability - the fourth "A".

PMID- 15501114
TI  - One year, and counting, after publication of our ACS "Code of Professional
      Conduct".

PMID- 15501115
TI  - Honesty is the ONLY policy: physician expert witnesses in the 21(st) century.

PMID- 15501116
TI  - What's new in general surgery: gastrointestinal conditions.

PMID- 15501117
TI  - Of the Billroths and Beethovens.

PMID- 15501119
TI  - Functional independence after major abdominal surgery in the elderly.
AB  - BACKGROUND: Elders undergo approximately 40% of more than 1 million major
      abdominal operations annually. Yet evidence about recovery to preoperative levels
      of functional independence is limited. This study details course and predictors
      of functional recovery after elective major abdominal operations in the elderly.
      STUDY DESIGN: This was a prospective cohort of 372 consecutive patients, 60 years
      old or more, enrolled from surgeons in private practice and two university
      affiliated hospitals, assessed preoperatively and postoperatively at 1, 3, and 6
      weeks, 3 and 6 months, using self-report and performance-based measures
      (Activities of Daily Living [ADL], Instrumental Activities of Daily Living
      [IADL], Medical Outcomes Study Short Form-36 Physical Component and Mental
      Component Scales [PCS, MCS], Geriatric Depression Scale [GDS], Folstein Mini
      Mental State Exam [MMSE], timed walk, functional reach, hand grip strength).
      RESULTS: Mean age was 69 +/- 6 years with 56% men, 47% nonHispanic Caucasian, and
      42% Mexican American; hospital distribution was 49% private, 51% university
      affiliated. Maximum functional declines (95% CI) occurred 1 week postoperatively:
      ADL, 2.8 points (2.4 to 3.2); IADL, 7.6 points (7 to 8.3); SF-36 PCS, 6.5 points
      (5.4 to 7.6); Mini-Mental State Exam, 0.5 points (0.2 to 0.7); timed walk, 6.8
      seconds (5.2 to 8.4); functional reach, 1.7 inches (1.2 to 2.2); grip strength, 2
      kilograms (1.3 to 2.7) (p < 0.001 for all). SF-36 mental component scale and
      Geriatric Depression Scale scores did not worsen. Mean recovery times were: Mini
      Mental State Exam, 3 weeks; timed walk, 6 weeks; ADL, SF-36 PCS, and functional
      reach, 3 months; and IADL, 6 months. Mean grip strength did not return to
      preoperative status by 6 months. The incidence of persistent disability at 6
      months, compared with preoperative status, was: ADL, 9%; IADL, 19%; PCS, 16%;
      mental component scale, 17%; timed walk, 39%; functional reach, 58%; and grip
      strength, 52%. Potentially modifiable independent predictors of ADL and IADL
      recovery were preoperative physical conditioning and depression plus serious
      postoperative complications. CONCLUSIONS: The clinical course of functional
      recovery varied across different measures. Protracted disability at 6 months
      after operation was substantial. Several potentially modifiable factors
      consistently predicted recovery.

PMID- 15501120
TI  - Thoracic surgery in the elderly.

PMID- 15501121
TI  - Nutritional concerns in the older surgical patient.

PMID- 15501122
TI  - General surgery as a career: a contemporary review of factors central to medical
      student specialty choice.

PMID- 15501123
TI  - Lymphatic mapping and sentinel lymph node biopsy in breast cancer patients: a
      comprehensive review of variations in performance and technique.

PMID- 15501124
TI  - John Harvey Kellogg; surgeon, inventor, nutritionist (1852-1943).

PMID- 15501125
TI  - Bilateral parathyroid cystic adenomas.

PMID- 15501126
TI  - Pelvic sepsis after stapled hemorrhoidectomy.

PMID- 15501127
TI  - Transdiaphragmatic radiofrequency ablation of liver tumors.

PMID- 15501128
TI  - Surgical repair of the abdominal bulge: correction of a complication of the flank
      incision for retroperitoneal surgery.

PMID- 15501129
TI  - Burns and metabolism.

PMID- 15501130
TI  - Sacral resection in cancer surgery.

PMID- 15501131
TI  - Fundoplication for laryngopharyngeal reflux disease.

PMID- 15501134
TI  - Molecular mechanisms in CNS injury--the importance of therapeutic modification of
      cytokine expression in the brains of domestic animals.

PMID- 15501135
TI  - Comparative aspects of blood coagulation--the road to new investigative fields
      within veterinary haemostasis.

PMID- 15501136
TI  - Urolithasis in pig units--a gritty problem.

PMID- 15501137
TI  - Evaluation of natural service bulls--the "other" BSE.

PMID- 15501138
TI  - The transport of animals: a long way to go.

PMID- 15501139
TI  - Evaluation of fertility and infertility in natural service bulls.
AB  - The potential fertility of bulls can be evaluated in the field by assessment of
      mating ability and physical examination. Both methods are useful for screening
      out low fertility bulls, although neither allows precise determination of the
      pregnancy rates that bulls actually achieve. Observations of coitus, libido
      testing and service capacity testing are the main methods of assessing mating
      ability in the field and, although not reliable for virgin bulls, are widely used
      for older bulls. Of the traits that are assessed during physical examination,
      those most closely correlated with fertility are scrotal circumference and the
      semen quality parameters of motility and morphology. Whilst these methods allow
      reasonable accuracy in determining the fertility potential of an individual bull,
      they do not take into account other managemental constraint to bulls' fertility.
      Although these are reasonable well understood for beef herds, the managemental
      factors that affect the performance of natural service sires in dairy herds are
      poorly understood.

PMID- 15501140
TI  - CNS injury: the role of the cytokine IL-1.
AB  - Injury to the central nervous system (CNS) and the resulting neuronal loss
      contribute significantly to morbidity and mortality in human and domestic animal
      populations. Most insults induce inflammation and the expression of cytokines.
      The specific roles of these proteins in neurological damage and repair are not
      completely understood. However, members of the interleukin-1 (IL-1) family have
      clear therapeutic potential: the IL-1 agonists, IL-1 alpha and IL-1 beta, are
      induced by CNS injury, and central injection of IL-1 increases, whilst peripheral
      or central administration of the IL-1 antagonist, IL-1ra, reduces the extent of
      the damage by more than 50%. The mechanism of action of these cytokines is the
      subject of intense research. In this review, we summarise approaches that are
      being used to investigate neuronal cell death, and the contribution of
      inflammation and cytokines, in particular the IL-1 family, to neurodegenerative
      disorders.

PMID- 15501141
TI  - Comparative aspects of blood coagulation.
AB  - Blood coagulation is a basic physiological defense mechanism that occurs in all
      vertebrates to prevent blood loss following vascular injury. In all species the
      basic mechanism of clot formation is similar; when endothelium is damaged a
      complex sequence of enzymatic reactions occurs that is localized to the site of
      trauma and involves both activated cells and plasma proteins. The reaction
      sequence is initiated by the expression of tissue factor on the surface of
      activated cells and results in the generation of thrombin, the most important
      enzyme in blood clot formation. Thrombin converts soluble fibrinogen, via soluble
      fibrin monomers, into the insoluble fibrin that forms the matrix of a blood clot
      as well as exerting positive-feedback regulation that effectively promotes
      additional thrombin generation that facilitates the rapid development of a
      thrombus. Both spontaneous and trauma-induced haemorrhagic episodes can develop
      in all mammals with inherited or acquired abnormalities in one or more of the
      coagulant proteins. Experimental studies with plasma from a wide range of species
      have led to the conclusion that there are extensive differences in the rates of
      thrombin generation and fibrin formation among species. However, current evidence
      suggests that at least some of these quantitative differences are likely due to
      the use of non-species specific laboratory reagents. Although the individual
      proteins involved in the procoagulant pathways exhibit similar functions in all
      animals, differences in amino acid sequence cause incomplete homology and varying
      degrees of immunological cross-reactivity for the same protein across species.

PMID- 15501142
TI  - Outcome of tactile conditioning of neonates, or "imprint training" on selected
      handling measures in foals.
AB  - Behavioural reactions to selected handling procedures were compared between
      conditioned, or imprint-trained, and untrained foals raised on the same farm.
      Nineteen randomly chosen healthy foals were imprint trained at birth and 24 h
      later (Group A). Twenty-one similar foals that were not imprint-trained served as
      age-matched controls (Group B). Training began within 10 min of birth and
      consisted of touch desensitization by gentle rubbing. Each tactile stimulus was
      repeated 30-50 times over 45-60 min, until the foal no longer resisted the
      procedure and appeared relaxed. The procedure was then repeated at 24 h of age.
      At that time a physical examination and blood analysis were performed to assess
      the foals' health status. Group B animals were not handled except for a brief
      physical examination and blood analysis at 24 h of age. Thereafter all foals were
      kept on pastures with their dams with no further handling until they were three
      months of age. Any foals handled for other reasons before that time were excluded
      from the study. At three months, each of the 28 foals that completed the study
      experienced the following handling procedures: acceptance of restraint,
      haltering, complete physical examination, acceptance of a plastic rebreathing
      bag, touching the whole body, intramuscular vaccination in the neck, intranasal
      vaccination, and deworming with oral paste. Response to each procedure was scored
      (1=not resistant, 2=low resistance, 3=strong resistance, 4=not possible without
      major physical restraint). Conditioned foals (Group A) were significantly less
      resistant to touching the front and hind legs and picking up the hind feet (P <
      0.05). The administration of vaccines and paste dewormer and the collection of
      blood were tolerated by the majority of the foals of both groups with no or low
      resistance. It appeared that neonatal imprint training resulted in a learned
      behaviour that resulted in decreased self-defence responses towards handling the
      limbs at three months of age.

PMID- 15501143
TI  - Influence of breathing pattern and lung inflation on impulse oscillometry
      measurements in horses.
AB  - The objective of this paper was to determine if changes in ventilation patterns
      could influence the outcome of respiratory function measurements performed with
      our impulse oscillometry system (IOS) in horses. In a first study, IOS tests were
      performed in vitro on six isolated equine lungs. Lung inflation levels were
      controlled by modifying depressurisation inside an artificial thorax and
      different ventilation patterns were imposed. In a second in vivo study, transient
      variations in breathing pattern were evaluated both with the IOS and a current
      reference technique (CRT) in five healthy mature horses after an intravenous
      (i.v.) injection of lobeline hydrochloride. In both studies, respiratory rate
      (RR, range: 7-42 breaths/min.) and tidal volume (V(T), range: 0.4-25 L) had minor
      or no influence on IOS parameters. The influence of lung inflation, most marked
      for resistance at 5 Hz (R(5 Hz)), was limited for the considered physiological
      range. In vivo, statistical models indicated that maximal changes in pleural
      pressure (Max Delta Ppl) and peak flows were the main determinants of the
      variability of the resistance (R(rs)) and the reactance (X(rs)) of the
      respiratory system. The fourfold increase in baseline Max Delta Ppl and peak
      flows obtained during hyperpnoea caused a significant increase in R(rs) at 5 and
      10 Hz and a decrease in X(rs) at all frequencies. We conclude that IOS parameters
      are not influenced by tachypnoea, but will reflect alterations in respiratory
      mechanics caused by hyperpnoeic breathing.

PMID- 15501144
TI  - Studies on platelet aggregation using the Born method in normal and uraemic dogs.
AB  - Using the Born method, based on light transmission in platelet rich plasma, the
      minimum effective concentration (threshold values) of several platelet agonists
      for inducing maximum platelet aggregation was determined in healthy dogs. The
      final concentrations of aggregation agonists were as follows: adenosine
      diphosphate (ADP) (0.5-50 micromol/L; n = 75 healthy dogs), collagen (0.5-20
      mg/mL; n = 75), thrombin (0.1-5 IU/mL; n = 75), ristocetin (1-10 mg/mL; n = 10),
      and epinephrine (5-50 micromol/L; n = 10). Reference values for maximum
      aggregation with a lower limit of > 80% were achieved for agonist concentrations
      25 micromol/L ADP (80-98%), > or = 10 microg/mL collagen (80-96%), and > or = 1
      IU/mL thrombin (80-97%). None of the concentrations of epinephrine and ristocetin
      used in this study induced quantitative aggregation in the whole group of healthy
      dogs. We also studied platelet aggregation in 14 uraemic dogs using selected
      concentrations of aggregation agonists. Aggregation was significantly decreased
      in uraemic dogs using intermediate agonist concentrations, i.e., in the region of
      the threshold concentration. In contrast, maximum aggregation was increased in
      uraemic patients compared to reference values using low concentrations of all
      three agonists (ADP: 1 micromol/L, collagen: 1 microg/mL, and thrombin: 0.1, 0.2
      IU/mL).

PMID- 15501145
TI  - Whole body barometric plethysmography: a screening method to investigate airway
      reactivity and acute lung injuries in freely moving pigs.
AB  - The aim of this work was to investigate whether the Penh index, measured using
      whole body barometric plethysmography, can be used as a screening parameter to
      evaluate the airway reactivity and the intensity of the pulmonary response to
      endotoxins. Penh was firstly recorded in non-sedated freely moving piglets
      exposed (1) to a nebulized acetylcholine (Ach) pre-treated or not with
      clenbuterol, or (2) to endotoxin challenge. To measure Penh simultaneously with
      total pulmonary resistance (R(L)), dynamic compliance (C(dyn)) and intrapleural
      pressure changes (Max Delta Ppl), an oesophageal balloon catheter technique was
      used and the piglets were anaesthetised. The recordings were performed during (1)
      an intravenous metacholine (Mch) challenge and (2) in endotoxin-exposed animals.
      In freely moving animals, Ach induced a significant dose-dependent increase in
      Penh, which was significantly blocked by clenbuterol. Endotoxin instillation also
      resulted in a significant rise in Penh while the corresponding response measured
      under anaesthesia was significantly and positively correlated with R(L) and Max
      Delta Ppl. Similar results were obtained during Mch challenge but the Penh was
      negatively correlated with C(dyn). We conclude that Penh could be used in freely
      moving piglets as a screening index for airway reactivity and pulmonary
      functional changes in cholinergic and endotoxin challenges.

PMID- 15501146
TI  - The oestrous cycle and early pregnancy--a new concept of local endocrine
      regulation.
AB  - Facts discovered in recent decades have compelled us to revise long-established
      views on the physiological regulation of cyclic adjustments to the reproductive
      system in preparation for pregnancy in females. Evidence has been presented to
      show that changes in the uterine blood supply induced by the
      oestrogen/progesterone ratio in the blood and cytokines are important in the
      regulation of the secretory function of the endometrium. Progressive reduction in
      uterine blood flow during the luteal phase of the oestrous cycle causes
      regressive changes in endometrial cells and release of prostaglandin (PG) F(2
      alpha), resulting in initiation of luteolysis. Retrograde transfer of PGF(2
      alpha) in the area of the mesometrium vasculature is an important element in the
      mechanism protecting the corpora lutea against luteolysis before day 12 of the
      porcine oestrous cycle and during early pregnancy and pseudopregnancy. Results of
      many studies presented in this review indicate that PGF(2 alpha) pulses in
      uterine venous blood during the follicular phase of the oestrous cycle may not be
      due to PGF(2 alpha) secretion by endometrial cells, but occur due to remodeling
      of the endometrium and pulsatile exretion of PGF(2 alpha) in accordance with
      rhythmic uterine contractions caused by oxytocin.

PMID- 15501147
TI  - Road transportation affects blood hormone levels and lymphocyte glucocorticoid
      and beta-adrenergic receptor concentrations in calves.
AB  - The effect of transportation on blood cortisol and catecholamine levels,
      lymphocyte glucocorticoid receptor (GR) and beta-adrenergic receptor (beta-AR)
      concentrations was investigated in calves. Blood samples were collected from 24
      six-month-old calves before departure (T(0)), on arrival (T(1)), and at 24 h
      (T(2)) and one week (T(3)) after arrival. Animals were loaded and transported
      about 950 km, from the Midy-Pyrenes region (Cahors, France) to the Piedmont
      region (Italy), over a total of 14 h. Serum cortisol levels and plasma
      catecholamines (adrenaline, noradrenaline) were determined by radioimmunoassay.
      Lymphocyte GRs and beta-ARs were measured through binding assays. A significant
      (P < 0.05) increase in cortisol and catecholamine concentrations was observed
      immediately after transport. The increase in hormone levels at time T(1) was
      negatively correlated with lymphocyte GR and beta-AR concentrations. At times
      T(2) and T(3), blood cortisol and catecholamine levels and lymphocyte GRs and
      beta-ARs returned to normal. The results demonstrate the activation of the
      hypothalamic-pituitary-adrenal axis and the catecholaminergic system in long-term
      transported calves. However, these systems returned to normal within 24 h after
      the end of transport.

PMID- 15501148
TI  - Vertical ground reaction force-time histories of sound Warmblood horses trotting
      on a treadmill.
AB  - The objective of this study was to establish representative treadmill ground
      reaction force (GRF) and interlimb co-ordination time data of clinically sound
      horses at the trot. It was anticipated that these normative standards would
      provide a reference data base against which lame horses could be compared. GRF
      time histories were collected from 30 Warmblood riding horses with easy, wide
      natural gaits. Data were recorded of all four limbs simultaneously by the use of
      an instrumented treadmill. A total of 912 stride cycles per limb were analysed
      for force, time and spatial parameters and were averaged. The shape and amplitude
      of the treadmill force curves were very similar to force traces recorded with a
      stationary force plate. The horses showed a high degree of symmetry in all
      investigated parameters (95% reference interval of left-right asymmetry +/-1.8
      6.8%). No significant differences were found between left and right mean values.
      Intra-individual coefficients of variance of the various parameters did not
      exceed 2.7%. Inter-individual coefficients of variance were 2.5-3.5 times larger
      than the respective intra-individual coefficients. An instrumented treadmill
      provides a number of decisive advantages, such as time-efficient data acquisition
      of all four feet simultaneously over successive strides, or the high regularity
      of the horse's gait pattern at controlled velocities, which allow the clinical
      assessment of locomotor performance of horses.

PMID- 15501149
TI  - Disposition of norfloxacin in broiler chickens and turkeys after different
      methods of oral administration.
AB  - Norfloxacin was administered orally to chickens and turkeys at 15 mg/kg body
      weight by pulse dosing at 24 h intervals and by continuous dosing at 100 mg/L in
      drinking water for five days. Blood samples were taken serially. Plasma
      norfloxacin concentrations were determined by high-performance liquid
      chromatography. The plasma norfloxacin concentrations increased slowly during
      continuous dosing and reached the MIC(90) (250 ng/mL) for Gram-negative pathogens
      by 12 h in chickens and 18 h in turkeys. The steady-state plasma concentration
      was attained in 36 h and remained at approximately 776.67+/-33.23 ng/mL in
      chickens and 682.50+/-28.55 ng/mL in turkeys. After pulse dosing, the plasma
      norfloxacin concentrations increased rapidly and exceeded the MIC(90) at 2 h in
      both species and remained above MIC(90) for 8 h in chickens and 6 h in turkeys.
      Pulse dosing provided half the steady-state concentration that was achieved by
      continuous dosing, 365.32+/-39.31 ng/mL in chickens and 306.03+/-32.26 ng/mL in
      turkeys, during the dosing interval of 24 h. Data for daily pulse dosing
      suggested that every administration corresponded to a single, daily repeated
      bolus administration although pulse dosing produced higher plasma concentrations
      more readily. Continuous and pulse dosing are both rational for the
      administration of norfloxacin to flocks of chickens and turkeys. We recommend
      that treatment be commenced with a pulse oral dose administered over a 4 h period
      and maintained by continuous oral medication for three to five consecutive days.

PMID- 15501150
TI  - Urolithiasis in finishing pigs.
AB  - Urolithiasis in sows and neonatal pigs is well-known, but information on its
      occurrence and impact in finishing pigs is sparse. This study reports three
      outbreaks of urolithiasis in finishing pigs. In one herd, no symptoms were
      observed, whereas in the other herds the presence of calculi caused obstruction
      of the urinary tract resulting in death. Using infra-red spectroscopy, the
      predominant mineral-type found in the uroliths was calcium carbonate (calcite).
      Only small amounts of calcium oxalate (< 1%) could be detected. A high urinary
      pH, small abnormalities in the mineral composition of the feed and insufficient
      drinking water were the most important risk factors identified. To prevent
      urolithiasis, it is important to ensure adequate water intake, to provide a
      balanced mineral diet, and to avoid urinary tract infections.

PMID- 15501151
TI  - Investigations on the influence of serum D-lactate levels on clinical signs in
      calves with metabolic acidosis.
AB  - Correlations between the degree of acidosis and clinical signs (changes in
      posture, behaviour, intensity of suckling reflex) in neonatal diarrhoeic calves
      have been described in various studies. However, base excess values varied widely
      in calves exhibiting similar clinical symptoms. The objective of this study was
      to elucidate whether the clinical picture of acidotic calves with neonatal
      diarrhoea is influenced more by D-lactate concentration than by degree of
      acidosis. Eighty calves up to three weeks old that were admitted to the II
      Medical Animal Clinic with acute diarrhoea and base excess values between -10 and
      -25 mmol/L were included in the prospective study. Posture, behaviour, suckling
      and palpebral reflexes, and position of the eyeballs were scored during the
      initial examination. Base excess and serum D-lactate and urea concentrations were
      determined in venous blood. In order to quantify the influences of base excess
      and d-lactate on the clinical parameters, groups of different clinical categories
      were compared. The results show that variations in behaviour, and in posture can
      be better explained by elevations of serum D-lactate concentrations than by
      decreases in base excess. Disturbances of the palpebral reflex appear to be
      almost completely caused by high levels of D-lactate.

PMID- 15501152
TI  - Generation and purification of recombinant bovine pregnancy associated
      glycoprotein.
AB  - Bovine pregnancy-associated glycoprotein-1 (bPAG-1) is predicted to play an
      essential role during pregnancy and is labelled as a potential biochemical marker
      of pregnancy in ungulates. We have compared the generation of the glycosylated
      form of recombinant bPAG-1 (rbPAG-1) by human embryonic kidney 293 (HEK 293) and
      Chinese hamster ovary (CHO) cells in attached cultures and evaluated the
      adaptation of the rbPAG-1 transfected cell line to suspension culture. The PAG
      cDNA was cloned from placental RNA obtained from a slaughtered cow on day 55 of
      pregnancy. The PAG-pRcRSV expression vector was transfected into HEK 293 and CHO
      cells. Western blot analysis showed that clonal HEK 293 cells expressed rbPAG-1
      better than CHO cells in attached cultures. Transfected HEK 293 cells were
      adapted to suspension culture in spinner flasks and the rbPAG-1 purified to
      homogeneity using ion-exchange, pepstatin-sepharose affinity chromatographies and
      preparative SDS-PAGE. The expression of rbPAG-1 was immunocharacterised using a
      polyclonal antibody. Our findings indicated that 293 cells are suitable for
      production of glycosylated form of rbPAG-1 and that the availability of the
      recombinant glycoprotein will aid in further studies to elucidate the function
      and structure of the protein.

PMID- 15501153
TI  - Age-specific seroprevalence of Border disease virus and presence of persistently
      infected sheep in Basque dairy-sheep flocks.
AB  - Using p125/p80 antibody and antigen-ELISA tests, age-specific seroprevalence and
      presence of persistently infected (PI) sheep were investigated in six commercial
      latxa dairy-flocks, housed for variable periods. The flocks all had a recent
      history of Border disease (BD). Every flock included seropositive sheep and seven
      0.5-3-year-old PI sheep were detected in two of four flocks tested. Age-specific
      antibody patterns differed according to the presence or absence of PI sheep in
      the flock. In flocks free of PI sheep, seroprevalence was 6-13% in 1-year-old
      sheep and 42-93% in older sheep. In contrast, seroprevalence was 67-99% in sheep
      raised with PI sheep for at least 1 year and 29-33% in replacement 0.5-0.6-year
      old sheep (including a PI sheep) indicating that Border disease virus (BDV)
      transmission in Basque dairy-flocks can be relatively slow. Moderate
      seroprevalence in young replacement sheep should not discourage further testing
      to detect PI sheep, and our results highlight the risk of failing to achieve
      "natural vaccination" prior to pregnancy by mixing PI sheep with BDV-unexposed
      ewes.

PMID- 15501154
TI  - Portable haemoglobinometers and their potential for penside detection of anaemia
      in bovine disease diagnosis: a comparative evaluation.

PMID- 15501155
TI  - PCR assay for rapid detection of Pasteurella multocida serogroup A in morbid
      tissue materials from chickens with fowl cholera.

PMID- 15501156
TI  - Magnetic resonance imaging of the normal brain in a newborn dromedary camel.

PMID- 15501157
TI  - Pathological changes in Sarcocystis infection in domestic pigs (Sus scrofa).

PMID- 15501159
TI  - [Impact of reverse transcriptase inhibitors on sperm mitochondrial and genomic
      DNA in assisted reproduction techniques].
AB  - For the last ten years, antiretroviral therapy (ARV) has improved the prognosis
      in HIV-1 infection and showed a better control of the viral excretion by reducing
      viral shedding in semen. However, nucleoside analogues reverse transcriptase
      inhibitors (NRTI) therapy reported important adverse effects. Most of these side
      effects observed seem to be linked with a common mechanism: mitochondrial
      activity alteration. Since the introduction of protocols for HIV-1 serodiscordant
      couples, with male infected partners under NRTI therapy, many results in the
      literature such as: semen characteristics and pregnancies, drew the attention of
      research teams. Many studies have suggested that NRTI has an affect on semen
      parameters, but proposed mechanisms of these effects have rarely been discussed.
      NRTI have a great affinity for the reverse transcriptase of HIV-1. Because many
      NRTI are not only inhibitors of reverse transcriptase but also inhibitors of the
      DNA polymerase beta and gamma, several toxic effects can be considered.
      Nevertheless, this specificity is not absolute and "accidental" incorporations of
      NRTI can occur on genomic sperm DNA. Only one study on genomic sperm DNA with
      patients under NRTI therapy was published without concluding results. Recently,
      studies have suggested that NRTI exposure could induce an alteration on
      mitochondrial energy-generating ability of spermatozoa. NRTI are known to induce
      an increase in the generation of reactive oxygen species, which results in the
      degradation of mitochondrial transmembrane potential (Deltapsim). This loss of
      Deltapsim can tend to release some specific apoptosis factors, such as cytochrome
      c, that initiates programmed cell death. Sperm DNA fragmentation, associated to
      apoptosis, was reported as a possible cause of recurrent pregnancy loss. If the
      incorporation of NRTI was reported in genomic DNA of somatic cells, the absence
      of data on the genomic sperm DNA justifies further studies concerning the effects
      of paternal exposure to NRTI on the genomic material of the male gamete, in
      particular because of its implication in the zygote development after
      fertilization.

PMID- 15501160
TI  - [Sacrospinous colpopexy complications].
AB  - OBJECTIVE: To evaluate complications of sacrospinous ligament fixation. DESIGN:
      Monocentric retrospective study. SETTING: Department of Obstetrics & Gynecology,
      La Conception University Hospital, Marcella. PATIENTS AND METHODS: Between
      January 1991 and September 2002, 277 women (mean age 64.9 years, range 37 to 92
      years) underwent a sacrospinous ligament fixation; 91% had a menopausal status,
      and 15.5% used hormone replacement therapy. 33.2% of the patients had prior
      hysterectomy, 28.9% had a history of surgery for prolapse, and 18.8% had
      associated symptoms of stress urinary incontinence. In all cases, sacrospinous
      ligament fixation was performed under visual control using conventional stitch.
      Sacrospinous ligament fixation was combined with the following procedures:
      anterior vaginal repair (N =137), additional incontinence surgery (N =31),
      vaginal hysterectomy (N =137), levator myorraphy (N =203). MAIN OUTCOME MEASURES:
      Intraoperative complications, postoperative complications, long-term painful
      symptoms. RESULTS: Intraoperative complications were represented by 1 case of
      vascular wound and four rectal injuries. Main postoperative complications were
      vaginal haematomas (N =6) and abscesses (N =2). Long-term symptoms were perineal
      pain, sciatic neuralgia, and dyspareunia. DISCUSSION AND CONCLUSION: There was no
      surgical mortality, and we noted low rates of major complications. Sacrospinous
      ligament fixation assumes high priority in our therapeutic regimen.

PMID- 15501161
TI  - [Vaginal birth after caesarean delivery in twin gestation: is trial of labor
      allowed?].
AB  - OBJECTIVE: To determine if a trial of labor in twin pregnancy with previous
      cesarean section is an acceptable alternative to systematic cesarean section.
      PATIENTS AND METHODS: Based on a retrospective and comparative study from 1st
      January 1996 to 30th June 2003 in Maternite Jeanne-de-Flandre (Lille) and
      Pavillon Paul-Gelle (Roubaix), 35 trials of labor in twin pregnancies with
      previous cesarean section have been compared with 35 twin gestations attempting
      vaginal delivery without a prior cesarean. This comparative study has been led by
      sorting out the patients according to their gestational age, parity and
      maternity. RESULTS: Twenty-seven women (77%) delivered vaginally and eight (23%)
      by elective caesarean section. Postpartum hemorrhage was more frequent for
      caesarean section (75%). No scare dehiscence or rupture occurred. There was not
      any haemostasis hysterectomy or embolisation related to postpartum haemorrhage.
      Neonatal outcome was similar in both groups. DISCUSSION AND CONCLUSION: Twin
      trial of labor after a previous cesarean section seems to be a safe alternative
      to routine repeat cesarean delivery as maternal and fetal morbidity and mortality
      are safe.

PMID- 15501162
TI  - [Pancreatic tumor revealed by metastatic bilateral ovarian tumor with
      virilisation syndrome].
AB  - We report a case of a 38-year-old patient presenting with both pancreatic and a
      bilateral ovarian tumor revealed by a virilization syndrome. Clinically, both
      tumors were conceivably distinct. However, on histological examination, they were
      found to be morphologically similar, with neuroendocrine features, suggesting
      that pancreatic tumor was a primitive neoplasm and the ovarian one a metastatic
      spread of that lesion. The virilization syndrome was due to the functional status
      of the ovarian tumors that was confirmed by immunohistochemical detection of
      inhibin.

PMID- 15501163
TI  - [Attachment and detachment].
AB  - Drawn as a conclusion to the colloquium of Bordeaux (June 2003), on mother-child
      attachment, these reflections open up to new venues. Indeed, the author makes the
      assumption that attachment and detachment make up a fundamental couple with
      attachment and detachment, which leads to getting one's autonomy, discovering the
      world and expressing one's pulsions. The very tension inside this antagonistic
      and fundamental couple--between attachment and pulsions--would be the origin of
      all forms of language.

PMID- 15501164
TI  - [Embryonic stem cells: a position for the obstetrician and gynaecologist. Part
      one].
AB  - Stem cells are undifferentiated cells, with the ability to self renew and to
      differentiate into specialised cells. Embryonic stem cells (ES) have proven to be
      truly pluripotent, since they are able to give derivatives of the three primitive
      embryonic layers. Human ES have a normal karyotype, maintain high telomerase
      activity, and exhibit remarkable long-term proliferative potential, providing the
      possibility for unlimited expansion in culture. Though human ES cell-based
      transplantation therapy holds great promises to successfully treat a variety of
      diseases (e.g., Parkinson's disease, diabetes, and heart failure) many barriers
      remain in the way of successful clinical trials. Less spectacular, the
      applications in the field of reproductive biology are also outstanding: stem cell
      biology will lead us to a better understanding of the cellular and molecular
      mechanisms of events such as infertility, failure of implantation, genomic
      imprinting and meiosis. The obstetrician and gynaecologist could act an important
      part in the production and study of embryonic stem cells. However, these data
      have to be integrated in the ethical and juridical background of embryonic stem
      cell research in France.

PMID- 15501166
TI  - [Intrauterine insemination: state-of-the-art in humans].
AB  - Despite its being used for a long time, intrauterine insemination (i.u.i.)
      remains debated as to its precise place and efficacy among assisted reproductive
      technologies. Data issued from the French Health Ministry inquiries are strictly
      limited to the number of cycles and the pregnancies and births including the
      multiple ones. Concerning 2000, more than 44,000 cycles were registered with 8%
      deliveries per cycle and 12% multiple pregnancies. Apart from the cervical female
      infertility which is considered to have the best prognosis with i.u.i.,
      literature data remain controversial with male and unexplained infertility.
      Prospective randomized studies are rather scarce, particularly when considering
      the inclusion of untreated control population. Meta-analyses have been published
      for ten years, which allowed to better define the place of i.u.i. in patient
      management. However one may notice that the sperm cut-off parameters for male
      infertility and the respective contribution of i.u.i. and ovulation treatment do
      not allow develop some evidence-based guidelines for i.u.i. good practice. Quite
      all meta-analyses modulated their conclusions by addressing the need for large
      randomized controlled studies. Such a need seems now quite reinforced since
      results were until now expressed as pregnancy rate per cycle or pregnancy rate
      per couple, whereas single live birth rate and drop out rate are claimed to be
      taken into account nowadays. Moreover the level of controlled hyperstimulation is
      highly questionable with both hyperstimulation ovary syndrome and multiple
      pregnancy risks. Patients facing with failed i.u.i. cycles may turn to i.v.f. or
      i.c.s.i.. Interestingly data coming from the French national register (FIVNAT)
      did not show major differences between couples turning to i.v.f. (i.c.s.i.) after
      previously failed i.u.i. cycles or using directly i.v.f. (i.c.s.i.). Moreover the
      prognostic as evaluated on pregnancy rate per cycle was unchanged between such
      patients, which does not support some selection of patients by i.u.i. failure.
      Thus, although i.u.i. seems likely a cost-effective treatment in infertile
      couples, the precise conditions of its management (spontaneous or stimulated
      cycle, mono-, pauci- or multi-follicular induction) remain to be assessed. Indeed
      large controlled randomized studies including untreated group are required even
      if such design might have a non negligible cost. However these rather common
      treatments do have a high cost and any effort to rationalise them will have some
      economical impact. Another practical approach, although less ambitious, might
      consist in developing a per cycle registry which should allow to precise the
      French practice at a large national level.

PMID- 15501167
TI  - [Insemination: history and state of the art in animals].
AB  - Insemination has been used since 1950 in the bovine and since the seventies in
      other domestic species. The use of insemination varies between the different
      species in terms of activity and method. The methods depend on the anatomical and
      physiological characteristics of each species, which lead to different sites of
      semen deposition and different minimal numbers of inseminated spermatozoa to
      obtain efficient fertility results. The use of frozen semen influences also the
      methods of insemination. Intra-uterine insemination is principally used when only
      small quantities of semen are available and/or to reduce the number of
      inseminated spermatozoa. Recent results in different species indicate that the
      use of intra-uterine insemination could be developed in the next years.

PMID- 15501168
TI  - [Chilled and frozen semen: the animal experience].
AB  - The aim of this paper is to describe technologies that are currently being used
      in animal reproduction and those that will be used in the near future. The
      significant changes (news methods of conservation of chilled and frozen semen)
      operated these last ten years in connection with the development of animal
      insemination are all detailed. All these techniques are experiencing rapid
      improvements in terms of success rate.

PMID- 15501169
TI  - [Artificial insemination with donor frozen sperm].
AB  - The cryopreservation of human sperm decreases its fecondity, by reduction in the
      number of motile sperm. However the fertilizing ability of the spermatozoa is not
      faded. The use of frozen sperm requires an optimization of the methods of
      artificial insemination to hope to approach the results obtained with fresh
      sperm. Intrauterine insemination with sperm selection meets this aim.

PMID- 15501170
TI  - [Intrauterine insemination: spontaneous or medically-assisted ovulation?].
AB  - Intrauterine insemination (i.u.i.) is usually proposed as the first-line therapy
      for infertility related to cervical factor, male and unexplained infertility. The
      overall success rate of i.u.i. is about 10-20% clinical pregnancies per cycle.
      i.u.i. may be performed in patients with or without prior controlled ovarian
      hyperstimulation (COH). The aim of COH is to closely monitor follicular growth in
      order to achieve a timely triggering of ovulation and i.u.i. Additionally,
      ovarian stimulation allows to increase the number of developing follicles.
      According to the review of previous prospective randomized studies and meta
      analyses, it seems that: (i) when a cervical factor is involved, the advantage of
      COH in conjunction with i.u.i. is likely but has to be confirmed; (ii) in male
      infertility, COH with gonadotropins in conjunction with i.u.i. increases the
      clinical pregnancy rate by two. In this situation, the better the sperm
      parameters are, the more advantageous COH is; (iii) in unexplained infertility,
      COH in addition to i.u.i. improves the pregnancy rate but stimulation with
      clomifene citrate appears to be less effective than gonadotropins administration.
      Beside the sperm parameters, the success rate depends on both woman's age and
      degree of ovarian stimulation. Meanwhile, ovarian hyperstimulation exposes to the
      risk of multiple pregnancy and hyperstimulation syndrome. Increasing the number
      of preovulatory follicles from one to two allows to approximately double the
      pregnancy rate. However, there is clear evidence that getting three or more than
      three follicles exposes to a worrying risk of multiple pregnancy. At the present
      time, the successful outcome of i.u.i. should not be assessed by the clinical
      pregnancy rate any longer but by the singleton birth rate. Our therapeutic
      strategy for COH prior to i.u.i. should take into account woman's age,
      infertility duration and associated infertility factors. The objective in terms
      of preovulatory follicle number must be determined prior to the stimulation in
      order to optimise the cycle outcome with a singleton birth.

PMID- 15501171
TI  - [Is there a future for Fallopian tube insemination in women?].
AB  - In unselected patients, the pregnancy rate after intrauterine insemination
      (i.u.i.) seldom goes beyond 10-15% per cycle. An insufficient number of
      spermatozoa at the fertilization site has been hypothesized for a long time to
      explain the low efficacy of this technique. Thus, the introduction of a larger
      number of male gametes into the female tubes has been thought of to give better
      results since the late eighties. First, a direct tubal catheterisation has been
      proposed for injection of spermatozoa, either by laparoscopy or transvaginally
      under ultrasound guidance or by tactile sensation. However, these procedures have
      been abandoned because of some severe traumatic and infectious complications.
      Alternatively, a spermatozoa suspension of several millilitres can be injected
      under pressure into the uterine cavity while sealing the cervical os, by various
      systems. This technique called Fallopian sperm perfusion (FSP) has yielded some
      interesting results, particularly in unexplained infertility. Nevertheless, the
      superiority of FSP over i.u.i. still remains controversial. This review describes
      the current knowledge about intratubal insemination and its potential role in the
      management of human infertility.

PMID- 15501172
TI  - [Deep intrauterine insemination in cattle].
AB  - INTRODUCTION: Most of the artificial inseminations in cattle nowadays are being
      performed in the uterine body with a rigid insemination device. Uterotubal
      junction insemination can only be performed in cattle with a device which is
      rigid enough to pass the cervix and flexible enough to follow the curvature of
      the uterine horns. At the Faculty of Veterinary Medicine in Ghent, a new
      insemination device has been developed for semen deposition near the utero-tubal
      junction in cattle and other animals. MATERIALS AND METHODS: In a first field
      trial the feasibility of the newly developed Ghent device was evaluated. Four
      thousand sixty-four dairy cows were inseminated by 12 inseminators with a
      standard insemination dose (10-15 million of frozen-thawed spermatozoa). Three
      insemination methods were compared; group 1: insemination in the uterine body
      with the conventional insemination device, group 2: insemination in the uterine
      body with the Ghent device, and group 3: insemination in the tip of both uterine
      horns with the Ghent device. In a second field trial insemination of dairy cows
      with the Ghent device was compared with the conventional insemination technique
      to evaluate the effect on pregnancy rates. The insemination dose was lowered to
      eight million (trial 1), four million (trial 2), and finally to two million
      frozen-thawed spermatozoa (trial 3). In each field trial, cows were divided into
      three groups: the first group was inseminated with a full insemination dose (12 x
      10(6)) in the uterine body with the conventional insemination device, the second
      group with a lowered insemination dose in the uterine body with the conventional
      insemination device, and the third group with a lowered insemination dose in the
      tip of both uterine horns with the Ghent device. It can be concluded that
      decreasing the insemination dose from 12 to four million frozen-thawed
      spermatozoa had no effect on pregnancy rate in our experiments, neither with the
      conventional insemination device, nor with the Ghent device. The device is made
      of disposable materials and has been tested to be non-toxic for bovine
      spermatozoa, can be used by one person and is adapted for application in the
      field. CONCLUSION: In the near future, similar field trials will be performed
      with even lower doses of semen. It is only in these cases that we truly hope to
      show a positive effect of uterotubal junction insemination by using low quality
      semen or by using sexed semen.

PMID- 15501173
TI  - [Role of intrauterine insemination as treatment for specific factor of
      fertility].
AB  - The role of intrauterine insemination as treatment for specific factor of
      infertility and for empiric treatment in idiopathic infertility is hereby
      described. A review of the different prerequisite evaluations is presented:
      ovarian age, pelvis evaluation and implantation parameters and negative lifestyle
      (woman weight and toxics). The efficiency of the treatment as evaluated by
      different studies is described in terms of pregnancy rate and obstetrical and
      perinatal outcome. In 2004, the treatment of idiopathic infertility by
      insemination/ovulation induction is challenged in the face of prevention of
      multiple pregnancies.

PMID- 15501174
TI  - Carotenoid hydroxylation--P450 finally!
AB  - Cytochrome P450 monooxygenases are involved in the biosynthesis of various
      compounds in plants such as phenylpropanoids, lipids and phytohormones.
      Hydroxylation of the carotenoid epsilon-ring is an essential reaction for the
      formation of lutein, the most abundant carotenoid in photosynthetic tissues.
      Recently, Li Tian and colleagues reported that a new P450 is responsible for this
      reaction. This discovery not only adds to the list of various functions of plant
      cytochrome P450s but also identifies one of the missing pieces of the puzzle of
      carotenoid biosynthesis.

PMID- 15501175
TI  - Rhizobium infection: lessons from the versatile nodulation behaviour of water
      tolerant legumes.
AB  - Water-tolerant legumes provide bacteria with special ways of invading roots to
      establish N(2)-fixing symbiosis upon flooding. On well-aerated roots, root hair
      curling (RHC) invasion is used, whereas, under hydroponic conditions, rhizobia
      enter the cortex through cracks at lateral root bases (LRBs). Here, we compare
      the physiological and anatomical traits of these invasions. During waterlogging,
      accumulating ethylene inhibits the epidermal stages of RHC invasion. LRB invasion
      circumvents this step by direct colonization of the cortical tissue. By avoiding
      the epidermis for bacterial entry under hydroponic conditions, the stringent
      nodulation (Nod) factor perception systems that are active within the epidermis
      are not needed. Consequently, LRB invasion might be useful for analysing the
      requirement for Nod factor perception and other signal transduction systems
      downstream of the epidermis.

PMID- 15501176
TI  - Plant fructan exohydrolases: a role in signaling and defense?
AB  - Fructans are fructose oligomers and polymers synthesized by a small number of
      plant and bacterial species and mainly function as reserve carbohydrates. The
      terminal fructosyl-fructose linkages can be degraded by fructan exohydrolases
      (FEHs), occurring in bacteria, fungi and fructan plants. Unexpectedly, it was
      found that FEHs also occur in non-fructan plants such as Beta vulgaris and
      Arabidopsis thaliana that apparently lack endogenous fructan substrates. FEHs
      might have defense-related roles acting on bacterial fructan-containing slimes or
      might act on minute (up to now undetected) amounts of fructans acting as signals
      in plants.

PMID- 15501177
TI  - Multiple functions of inducible plant volatiles.
AB  - A considerable amount of the carbon fixed by plants is emitted back into the
      atmosphere as volatile organic compounds (VOCs). Novel inducible VOCs released
      from plants after biotic or abiotic stresses temporarily increase total emissions
      of carbon substantially. As well as having a role in attracting the natural
      enemies of herbivores, inducible VOCs are also involved in plant-to-plant
      signalling, pathogen defence and ozone quenching, as well as tropospheric ozone
      and fine-particle aerosol formation. To relate these diverse observations to
      active plant defence, a conceptual framework of four functional levels (plant
      cellular interspace, leaf boundary layer, ecosystem and atmosphere) of inducible
      VOCs is proposed to aid understanding of the evolutionary role of inducible plant
      volatiles.

PMID- 15501178
TI  - Performing the paradoxical: how plant peroxidases modify the cell wall.
AB  - Since their appearance in the first land plants, genes encoding class III
      peroxidases have been duplicated many times during evolution and now compose a
      large multigene family. The reason for these many genes is elusive, and we are
      still searching for the specific function of every member of the family.
      Nevertheless, our current understanding implicates peroxidases as key players
      during the whole life cycle of a plant, and particularly in cell wall
      modifications, in roles that can be antagonistic depending on the developmental
      stage. This diversity of functions derives in part from two possible catalytic
      cycles of peroxidases involving the consumption or release of H(2)O(2) and
      reactive oxygen species (e.g. O(2)(-), H(2)O(2), OH).

PMID- 15501179
TI  - Plant serine/arginine-rich proteins and their role in pre-mRNA splicing.
AB  - Pre-messenger RNA (pre-mRNA) splicing, a process by which mature mRNAs are
      generated by excision of introns and ligation of exons, is an important step in
      the regulation of gene expression in all eukaryotes. Selection of alternative
      splice sites in a pre-mRNA generates multiple mRNAs from a single gene that
      encode structurally and functionally distinct proteins. Alternative splicing of
      pre-mRNAs contributes greatly to the proteomic complexity of plants and animals
      and increases the coding potential of a genome. However, the mechanisms that
      regulate constitutive and alternative splicing of pre-mRNA are not understood in
      plants. A serine/arginine-rich (SR) family of proteins is implicated in
      constitutive and alternative splicing of pre-mRNAs. Here I review recent progress
      in elucidating the roles of serine/arginine-rich proteins in pre-mRNA splicing.

PMID- 15501180
TI  - Short on phosphate: plant surveillance and countermeasures.
AB  - Metabolism depends on inorganic phosphate (P(i)) as reactant, allosteric effector
      and regulatory moiety in covalent protein modification. To cope with P(i)
      shortage (a common situation in many ecosystems), plants activate a set of
      adaptive responses to enhance P(i) recycling and acquisition by reprogramming
      metabolism and restructuring root system architecture. The physiology of P(i)
      starvation responses has become well understood, and so current research focuses
      on the initial molecular events that sense, transmit and integrate information
      about external and internal P(i) status. Recent studies have provided evidence
      for P(i) as a signaling molecule and initial insight into the coordination of
      P(i) deficiency responses at the cellular and molecular level.

PMID- 15501181
TI  - Fructose-2,6-bisphosphate: a traffic signal in plant metabolism.
AB  - Fructose-2,6-bisphosphate (Fru-2,6-P(2)) regulates key reactions of the primary
      carbohydrate metabolism in all eukaryotes. In plants, Fru-2,6-P(2) coordinates
      the photosynthetic carbon flux into sucrose and starch biosynthesis. The use of
      transgenic plants has allowed the regulatory models to be tested by modifying the
      Fru-2,6-P(2) levels and the enzymes regulated by Fru-2,6-P(2). Genes for the
      bifunctional plant enzyme that synthesizes and degrades Fru-2,6-P(2) have been
      isolated and molecular characterization has provided new insight into structure
      and molecular regulation of the enzyme. Advances in Fru-2,6-P(2) physiology and
      molecular biology are discussed. These advances have not only enlightened in vivo
      operation of Fru-2,6-P(2) but also revealed that the Fru-2,6-P(2) regulatory
      system is highly complex and interacts with other regulatory mechanisms.

PMID- 15501182
TI  - New developments in imaging for diagnosis and therapy monitoring in rheumatic
      diseases.
AB  - The availability of therapeutic modalities that are able to stop inflammatory
      joint damage has also markedly influenced recent developments in muskuloskeletal
      imaging. One focus of interest is the detection of joint pathology as early as
      possible in order to prevent erosive bony changes. Ultrasonography and magnetic
      resonance imaging are the most valuable technologies in this respect. Another
      focus is on the exact assessment and documentation of joint damage using scoring
      systems not only in therapeutic trials, but also in clinical practice. In
      addition to these recent advances in peripheral and axial joint imaging, this
      chapter also discusses advances in vascular imaging and scintigraphy in
      rheumatoid diseases as well as interventional procedures guided by imaging
      technologies.

PMID- 15501183
TI  - Differential diagnosis of rheumatic diseases using conventional radiography.
AB  - The approach to the differential diagnosis of rheumatic diseases using
      conventional radiography is systematic and module-oriented, which, with respect
      to future developments, forms the basis for computer-assisted diagnosis (CAD).
      The indications follow consensus-based referral criteria and attempts should be
      made to raise the evidence level of the recommendations. Investigation techniques
      have been improved in the last few years with the use of digital radiography. New
      imaging technologies may be available in the future that will achieve at least
      the same quality of images, while exposing patients to a significantly lower
      radiation dose. The interpretation of radiographical signs could be enhanced
      through a correlation with other imaging modalities. Computer-assisted techniques
      with image processing tools for automated measurements, lesion detection and in
      the form of expert systems are under development. With conventional radiography
      embedded in CAD systems, promising options will be available to enhance the
      differential diagnosis of rheumatic diseases.

PMID- 15501184
TI  - Musculoskeletal ultrasound.
AB  - Over the last few years a sonographic revolution has occurred in rheumatology.
      Ultrasonography has been shown to be capable of substantially changing the
      traditional approach to most clinical problems in daily rheumatological practice
      because of its ability to allow a quick, safe and inexpensive access to otherwise
      undetectable anatomical information on the early targets of most rheumatic
      diseases. Ultrasonography completes the physical examination in a rapid and
      accurate manner and allows the detection of a wide spectrum of pathological
      findings involving different anatomical structures in the musculoskeletal system.
      Guidance for intervention (joint aspiration, synovial or soft tissue biopsy,
      joint or tendon sheath injection) is a major application of ultrasonography.
      Sonographic guidance is particularly useful when fluid collections are very small
      or when the inflammatory process is adjacent to anatomical structures that could
      be seriously damaged by the injection.

PMID- 15501185
TI  - Doppler sonography in rheumatology.
AB  - The importance of ultrasonography in rheumatology has increased dramatically
      within the last few years both with regard to clinical practice and to research.
      High-resolution colour Doppler ultrasound equipment is, to date, widely
      available. Colour and power Doppler studies of intra-articular and peritendinous
      blood flow allow an estimation of the inflammatory activity and aid in
      distinguishing anatomical structures. Contrast agent increases the ability of
      ultrasonography to detect even minor perfusion. These findings have a practical
      clinical impact on the management of inflammatory rheumatic diseases. The
      resolution of ultrasonography is superior to that of magnetic resonance imaging
      (MRI) and computed tomography (CT) with regard to superficial anatomical
      structures. Furthermore, ultrasonography can depict the artery wall in contrast
      to angiography. In temporal arteritis and Takayasu's arteritis, ultrasonography
      depicts characteristic, homogenous wall thickening, stenoses and acute
      occlusions. These pathologies resolve quickly with treatment in the temporal
      arteries and much more slowly in larger arteries.

PMID- 15501186
TI  - Quantification of radiological damage in inflammatory arthritis: rheumatoid
      arthritis, psoriatic arthritis and ankylosing spondylitis.
AB  - Quantification of radiological damage in inflammatory arthritis is important. It
      has proven its value in clinical trials, but its use in clinical practice is
      becoming more important as well. Scoring methods for rheumatoid arthritis,
      psoriatic arthritis and ankylosing spondylitis are available. These differ in the
      joints and features assessed. This results in differences in the scoring range,
      but also in the method of performance. The various methods for the three diseases
      are detailed in this chapter. Most information is available for rheumatoid and
      for this disease the relationship between radiological damage and long-term
      outcome is summarised.

PMID- 15501187
TI  - Magnetic resonance imaging of peripheral joints in rheumatic diseases.
AB  - The need for better methods than the conventional clinical, biochemical and
      radiographical examinations in the management of inflammatory joint diseases is
      evident, since these methods are not sensitive or specific to early pathologies
      and subtle changes. Magnetic resonance imaging (MRI) offers improved sensitivity
      to early inflammatory and destructive changes in peripheral joints in rheumatoid
      arthritis (RA) and, even though less well documented, in other inflammatory joint
      diseases. Good evidence is available that MRI bone erosions represent true bone
      abnormalities and are predictors of radiographical outcome in RA. Similarly,
      there is solid evidence for MRI synovitis representing true synovial inflammation
      and being of considerable practical, clinical and radiological significance in
      RA. Describing the encouraging current knowledge regarding MRI for diagnosis,
      monitoring and prognosis, this chapter discusses the potential for the use of MRI
      in the clinical management of patients with suspected and diagnosed inflammatory
      joint diseases, as well as research priorities and clinical situations where the
      use of MRI could be suggested.

PMID- 15501188
TI  - Magnetic resonance imaging of the axial skeleton in rheumatoid disease.
AB  - The axial skeleton is a target for both spondyloarthritis and rheumatoid
      arthritis. While conventional radiography allows the clear documentation of the
      late stages of inflammatory changes, magnetic resonance imaging (MRI) is
      sensitive enough to depict early inflammatory lesions. It is, therefore, of
      particular importance for radiologists and clinicians to know the MRI appearances
      of inflammatory changes of the axial skeleton in rheumatoid diseases. Typical
      lesions in ankylosing spondylitis and related conditions comprise spondylitis
      (Romanus lesion), spondylodiscitis (Andersson lesion), arthritis of the
      apophyseal joints, the costovertebral and costotransverse joints, and
      insufficiency fractures of the ankylosed vertebral spine (non-inflammatory type
      of Andersson lesion). Sacroiliitis is associated with chronic changes such as
      sclerosis, erosions, transarticular bone bridges, periarticular accumulation of
      fatty tissue and ankylosis. In addition, acute findings include capsulitis, juxta
      articular osteitis and the enhancement of the joint space after contrast medium
      administration. Another important sign of spondyloarthritis is enthesitis, which
      affects the interspinal and supraspinal ligaments of the vertebral spine and the
      interosseous ligaments in the retroarticular space of the sacroiliac joints. The
      main site of manifestation of spinal involvement in rheumatoid arthritis is the
      cervical spine. Typical changes are the destruction of the atlantoaxial complex
      by pannus tissue with subsequent atlantoaxial subluxation, basilar impression and
      erosion of the dens axis. Changes in the lower segments of the cervical spine are
      destruction of the apophyseal joints resulting in the so-called stepladder
      phenomenon. Because of the uniform response of the discovertebral complex to
      different noxae, a number of different conditions must be distinguished on the
      basis of the patient's clinical findings and history in combination with their
      imaging appearance. These conditions comprise degenerative disc disease, septic
      spondylodiscitis, Scheuermann's disease, Paget's disease and diffuse idiopathic
      skeletal hyperostosis (DISH).

PMID- 15501189
TI  - Scintigraphy in rheumatic diseases.
AB  - The aim of this review is to summarise the clinical role of nuclear medicine in
      rheumatology taking into consideration the most specific diagnostic applications
      and other worthwhile therapeutic contributions. Traditional bone scintigraphy and
      recent inflammation-targeting radiopharmaceuticals, such as radiolabelled
      leucocytes and immunoscintigraphy, now allow us to obtain highly sensitive total
      body and tomographical imaging information that can be used for the diagnosis of
      osteoarticular disease. The most common extra-articular manifestations of
      rheumatic diseases due to digestive, central nervous, respiratory and
      cardiovascular system involvement can be diagnosed by specific scintigraphic
      methods. Radiosynovectomy plays an important role in providing effective
      treatment for some joint diseases that are resistant to pharmacological therapy.
      Diagnostic and therapeutic applications of nuclear medicine show the highest
      efficacy in the early phase of rheumatic diseases. In more advanced stages,
      scintigraphical techniques play a complementary role to radiographical
      investigations in the assessment of prognosis and therapy efficacy.

PMID- 15501190
TI  - Imaging in early arthritis.
AB  - Imaging can play a vital role in the evaluation of patients with early arthritis.
      Various imaging methods can be utilized to aid with diagnosis, predict prognosis
      and follow disease progression and treatment response. Previously, conventional
      radiography was the principal method used to evaluate and follow bone damage in
      patients with inflammatory arthritis. More recently the use of magnetic resonance
      imaging and ultrasonography has gained wider acceptance and popularity due to the
      ability of these multiplanar techniques to image both bone changes and soft
      tissue abnormalities, including synovitis. This chapter discusses the current
      imaging modalities used in the evaluation of patients with early arthritis, as
      well as the use of imaging in establishing the extent of disease, in prognosis
      and in monitoring disease course. Current data on imaging of patients with early
      arthritis due to rheumatoid arthritis, psoriatic arthritis and ankylosing
      spondylitis is reviewed.

PMID- 15501191
TI  - Interventional radiology and the musculoskeletal system.
AB  - Imaging-guided interventional procedures are becoming increasingly important in
      clinical rheumatology, since arthrocentesis of peripheral joints and the spine,
      as well as soft tissue injections, have a high rate of para-articular
      localisation when performed as blind techniques. Ultrasound-guided needle
      placement is the method of choice for interventional procedures on peripheral
      joints and for soft tissue injections. Fluoroscopy and computed tomography (CT)
      are not recommended for these indications due to the application of ionising
      radiation and the high procedural effort. By contrast, CT and magnetic resonance
      imaging are preferred for a variety of percutaneous procedures on the spine and
      sacroiliac joints. The increasing use of these methods for interventional
      purposes should improve both technical and procedural quality, thus ensuring cost
      effectiveness and patient safety.

PMID- 15501192
TI  - Vascular imaging.
AB  - Many rheumatic diseases affect the vasculature, either as a 'primary'
      manifestation of the disease process (as in vasculitis or scleroderma-spectrum
      disorders) or as a result of accelerated atherosclerosis. Recent years have seen
      very major developments in, and refinements of, vascular imaging methods. It is
      likely that this pace of development will continue, enhancing the
      rheumatologist's ability to diagnose different musculoskeletal conditions and
      follow their progression, using minimally invasive techniques. In this chapter,
      we describe these recent advances in vascular imaging techniques, concentrating
      on those most relevant to the practising clinician, but also discussing methods
      which are being used in clinical research. Three main groups of imaging
      modalities are described: large vessel imaging (X-ray, magnetic resonance (MR)
      and computed tomography (CT) angiography), nailfold microscopy and thermography.
      For each of these, the method(s) and then the clinical and research applications
      are discussed. Laser Doppler, a research technique, is also described.

PMID- 15501193
TI  - A critical review of the pain readiness to change model.
AB  - Current approaches to treating chronic pain often incorporate a multidisciplinary
      approach and a focus on self-management. Although many of the patients who
      complete this type of treatment exhibit gains, there remain a significant
      proportion of patients who fail to engage in or complete this type of approach or
      who fail to adhere to treatment recommendations. In an attempt to address these
      issues, the construct of readiness (or motivation) to adopt a self-management
      approach to chronic pain has been described and has attracted research interest
      in recent years. Operationalization of the construct has led to the development
      of the Pain Stages of Change Questionnaire and other strategies for its
      assessment. Considerable discussion, debate, and ongoing research have expanded
      our understanding of motivation in the context of chronic pain treatment and have
      informed the articulation of potentially important ways in which self-management
      treatment approaches to chronic pain might be improved. The aim of this article
      is to review the work in this area and discuss implications for clinical practice
      and further research. PERSPECTIVE: This article reviews the research to date in
      the area of pain readiness to change. It provides readers with an overview of the
      current conceptualization of readiness and discusses important implications for
      multidisciplinary treatment interventions with a focus on self-management.

PMID- 15501194
TI  - On the relationship between self-report and facial expression of pain.
AB  - Several investigators have reported weak or no associations between self-report
      and facial expression of pain, concluding that both parameters appear to be
      unrelated. However, studies so far have only focused on an overall association,
      not considering psychophysical relationships between stimulus intensities and
      pain responses while computing correlations. In the present study these
      psychophysical relationships, between stimulus intensity on the one hand and
      response magnitudes (of self-report and facial expression) on the other hand,
      were described in terms of intercept and slope. Correlation analyses were
      conducted between intercept and slope parameters of self-report and facial
      expression of pain. Forty young, pain-free individuals were investigated for
      their responses to mechanically and electrically induced pain. Self-report was
      assessed by Visual Analog Scales. Facial expression was examined by using the
      Facial Action Coding System. There were significant correlations between the
      linear slopes of the psychophysical functions of self-report and facial
      expression in pressure pain. Neither the intercepts nor overall mean responses in
      the 2 pain-signaling systems were significantly correlated. These findings
      suggest that the facial expression of pain appears to mirror self-report ratings,
      when their increases over a range of increasing stimulus intensities are
      considered in parallel. PERSPECTIVE: In future studies, our psycho-physically
      derived observation that incremental changes in facial expression during
      developing pain are more characteristic for individuals than static levels needs
      further corroboration.

PMID- 15501195
TI  - Comparison of experimental and acute clinical pain responses in humans as pain
      phenotypes.
AB  - This study evaluates the sensitivity of normal subjects (N = 617; 369 women, 248
      men) to experimentally induced pain including thermal stimuli and the cold
      pressor test to delineate individual response patterns and pain phenotypes. A
      subset of subjects (n = 157; 99 women and 58 men) also underwent standardized
      oral surgery, and the responses to clinically induced acute inflammatory pain
      were evaluated. A wide range of pain responses was found in both the experimental
      and clinical situations. The latency for withdrawal in the cold pressor test
      exhibited a dichotomous distribution of short and long times. Women exhibited
      higher responses to cold (P < .001) and thermal stimuli (P < .05) than men.
      Ethnicity affected pain responses to thermal stimuli ranging from 43 degrees C to
      47 degrees C (P < .05) and cold stimuli (P < .001). However, neither gender nor
      ethnicity affected pain responses to clinically induced acute inflammatory
      stimuli. Cross-modality comparisons of responses within experimental pain showed
      strong correlations (P < .01) but weaker relationships with clinical inflammatory
      pain. These data suggest that the background factors and characteristics of
      experimental pain responses differ from those of clinical pain; therefore,
      experimental pain ratings alone are not sufficient to predict responses to
      clinically induced acute pain. PERSPECTIVE: The findings of the present study
      suggest that investigations of pain phenotypes should take into consideration the
      subjects' gender and ethnicity and the pain-inducing stimuli. The predictive
      value of experimental pain for clinically induced pain is weak and not reliable.

PMID- 15501196
TI  - Spinal neural cyclooxygenase-2 mediates pain caused in a rat model of lumbar disk
      herniation.
AB  - Application of nucleus pulposus to nerve root generates radicular pain. We
      demonstrated that these animals showed allodynia for 2 weeks, and cyclooxygenase
      2 (COX-2) immunoreactivities were up-regulated in the spinal dorsal horn. COX-2
      immunoreactivities were shown in neurons; however, they were not in astrocytes.
      Intrathecal administration of an antibody to COX-2 decreased allodynia. Our
      results suggest that COX-2 in spinal cord might be a target for treatment of
      patients with nerve root pain caused by lumbar disk herniation. PERSPECTIVE:
      Neural COX-2 might mediate nerve root pain in the spinal cord caused by lumbar
      disk herniation in rats.

PMID- 15501197
TI  - Spinal gap junctions: potential involvement in pain facilitation.
AB  - Glia are now recognized as important contributors in pathological pain creation
      and maintenance. Spinal cord glia exhibit extensive gap junctional connectivity,
      raising the possibility that glia are involved in the contralateral spread of
      excitation resulting in mirror image pain. In the present experiments, the gap
      junction decoupler carbenoxolone was administered intrathecally after induction
      of neuropathic pain in response to sciatic nerve inflammation (sciatic
      inflammatory neuropathy) or partial nerve injury (chronic constriction injury).
      In both neuropathic pain models, a low dose of carbenoxolone reversed mirror
      image mechanical allodynia, while leaving ipsilateral mechanical allodynia
      unaffected. Ipsilateral thermal hyperalgesia was briefly attenuated. Critically,
      blockade of mechanical allodynia and thermal hyperalgesia was not observed in
      response to intrathecal glycyrrhizic acid, a compound similar to carbenoxolone in
      all respects but it does not decouple gap junctions. Thus, blockade of mechanical
      allodynia and thermal hyperalgesia by carbenoxolone does appear to reflect an
      effect on gap junctions. Examination of carbenoxolone's effects on intrathecal
      human immunodeficiency virus type 1 gp120 showed that blockade of pain
      facilitation might result, at least in part, via suppression of interleukin-1
      and, in turn, interleukin-6. These data provide the first suggestion that spread
      of excitation via gap junctions might contribute importantly to inflammatory and
      traumatic neuropathic pain. PERSPECTIVE: The current studies provide evidence for
      involvement of gap junctions in spinal cord pain facilitation. Intrathecal
      carbenoxolone, a gap junction decoupler, reversed neuropathy-induced mirror image
      pain and intrathecal gp120-induced allodynia. In addition, it decreased gp120
      induced proinflammatory cytokines. This suggests gap junction activation might
      lead to proinflammatory cytokine release by distantly activated glia.

PMID- 15501198
TI  - Sex differences in the long-term stability of forehead cold pressor pain.
AB  - The purpose of this study was to examine sex differences in the stability of
      experimental pain responding across time. Stability was assessed by using 2
      forehead cold pressor applications separated by 9 months. Twenty-eight men and 20
      women completed both Session 1 and Session 2. Repeated measures analysis of
      variance showed a main effect for Session on maximum pain level. Women reported
      significantly more pain at Session 2, whereas men showed no difference between
      sessions. There were no differences on pain report between men and women at
      Session 1. A significant Session by Sex interaction was associated with perceived
      chronic stress and trait anxiety levels. At Session 2 but not Session 1, women
      endorsed a significantly greater expectation than men to experience unpleasant
      aftereffects from the cold pressor task. Additional analysis showed that chronic
      stress and trait anxiety were significantly associated with sex-specific pain
      responding. We propose that the influence of a prior painful incident on an
      identical repeated painful experience differs between men and women. We speculate
      that this influence is related to sex differences in psychological mechanisms
      used to interpret painful stimuli within the context of remembered experiences.
      To our knowledge, this is the first report of sex differences in the long-term
      stability of an experimental laboratory pain stimulus, controlling for follicular
      phase of the female menstrual cycle. PERSPECTIVE: This study examines sex
      differences in the stability of experimental pain responding across a 9-month
      period. We speculate that psychological mechanisms influence one's interpretation
      of a prior painful incident and that this interpretation facilitates increased
      pain reporting in response to an identical repeated exposure, as was observed for
      women.

PMID- 15501199
TI  - Reimbursement denial and reversal by health plans at a university hospital.
AB  - PURPOSE: Denial and downgrading of reimbursement for hospital days are two
      strategies utilized by health plans to maintain profitability. The goal of this
      study was to describe patterns of discounted reimbursement at a university
      hospital. METHODS: We performed a retrospective cohort study of consecutive per
      diem patients hospitalized in 1999. We defined a discounted day as a day fully
      denied or downgraded and a reversal day as a day reimbursed at a higher level
      after appeal. The study outcomes included the probability of a discounted day and
      the probability of a discounted day to be later reversed. Covariance logistic
      regression was used to compare these outcomes by plan and physician specialty
      after adjusting for age, sex, race, length of stay, and diagnosis. Correlations
      with plan characteristics were analyzed. RESULTS: Of 59,265 hospital days, 6074
      days (10.2%) were initially denied or downgraded. On appeal, 1755 discounted days
      (28.9%) were reversed. The percentage of days discounted per plan ranged from
      1.2% to 18.8% (P <0.001), whereas the percentage of discounted days that were
      later reversed ranged from 23.2% to 85.3% (P <0.001). The qualitative magnitude
      of these associations and statistical significance were unchanged in adjusted
      models. Strong correlations were found between the adjusted odds ratio for a
      discounted day and net profit margin (R = 0.81) and medical loss ratio (R = 
      0.77). CONCLUSION: Denials and downgrades are frequent, with marked variation by
      health plan. More profitable plans had higher denial and discount rates. Evidence
      based standards for denials and downgrades are needed to maintain optimal patient
      care and the fiscal health of hospitals and health plans.

PMID- 15501200
TI  - Misdiagnosis of atrial fibrillation and its clinical consequences.
AB  - PURPOSE: Computer algorithms are often used for cardiac rhythm interpretation and
      are subsequently corrected by an overreading physician. The purpose of this study
      was to assess the incidence and clinical consequences of misdiagnosis of atrial
      fibrillation based on a 12-lead electrocardiogram (ECG). METHODS: We retrieved
      2298 ECGs with the computerized interpretation of atrial fibrillation from 1085
      patients. The ECGs were reinterpreted to determine the accuracy of the
      interpretation. In patients in whom the interpretation was incorrect, we reviewed
      the medical records to assess the clinical consequences resulting from
      misdiagnosis. RESULTS: We found that 442 ECGs (19%) from 382 (35%) of the 1085
      patients had been incorrectly interpreted as atrial fibrillation by the computer
      algorithm. In 92 patients (24%), the physician ordering the ECG had failed to
      correct the inaccurate interpretation, resulting in change in management and
      initiation of inappropriate treatment, including antiarrhythmic medications and
      anticoagulation in 39 patients (10%), as well as unnecessary additional
      diagnostic testing in 90 patients (24%). A final diagnosis of paroxysmal atrial
      fibrillation based on the initial incorrect interpretation of the ECGs was
      generated in 43 patients (11%). CONCLUSION: Incorrect computerized interpretation
      of atrial fibrillation, combined with the failure of the ordering physician to
      correct the erroneous interpretation, can result in the initiation of
      unnecessary, potentially harmful medical treatment as well as inappropriate use
      of medical resources. Greater efforts should be directed toward educating
      physicians about the electrocardiographic appearance of atrial dysrhythmias and
      in the recognition of confounding artifacts.

PMID- 15501201
TI  - Effectiveness of glucosamine for symptoms of knee osteoarthritis: results from an
      internet-based randomized double-blind controlled trial.
AB  - PURPOSE: To present the safety and effectiveness results of a prototypical 12
      week, double-blind, randomized placebo-controlled trial of glucosamine among
      subjects with knee osteoarthritis who were recruited and followed entirely over
      the Internet. METHODS: The study comprised 205 subjects aged 45 years or older
      with symptomatic knee osteoarthritis who were recruited over the Internet;
      eligibility was authenticated through medical record review. Participants were
      assigned randomly to 1.5 g/d of glucosamine (n = 101) or placebo (n = 104), of
      whom 108 completed the intervention (93 in each arm). The primary outcome measure
      was the pain subscale of the Western Ontario and McMaster Universities
      Osteoarthritis Index (Likert version). Additional outcome measures included the
      physical function and stiffness subscales and overall score of the questionnaire,
      and analgesic use. RESULTS: There was no difference between treatment and control
      groups in terms of change in pain score (2.0 +/- 3.4 vs. 2.5 +/- 3.8, P = 0.41),
      stiffness (0.7 +/- 1.6 vs. 0.8 +/- 1.5, P = 0.52), physical function (5.2 +/- 9.5
      vs. 4.6 +/- 9.6, P = 0.49), overall score (7.8 +/- 13.1 vs. 7.8 +/- 13.5, P =
      0.81), and analgesic use (133 +/- 553 vs. -88 +/- 755, P = 0.12). Stratification
      by osteoarthritis severity, glucosamine product, and use of a nonsteroidal anti
      inflammatory drug, as well as exclusion of opiate users, did not alter the
      results. The number and type of adverse events reported was similar between the
      groups. CONCLUSION: Our results suggest that although glucosamine appears to be
      safe, it is no more effective than placebo in treating the symptoms of knee
      osteoarthritis.

PMID- 15501202
TI  - Educational disadvantage impairs functional recovery after hospitalization in
      older persons.
AB  - PURPOSE: To determine whether low educational level is associated with poor
      functional recovery after hospitalization in older adults. METHODS: We followed
      862 patients (374 with low education, defined as <high school) for 6 months after
      hospitalization. Poor functional recovery was defined as an Activities of Daily
      Living score that was lower 6 months after hospitalization than 1 month before
      hospitalization. People who died were also considered to have poor recovery.
      RESULTS: Of the 862 participants, 351 (41%) experienced poor functional recovery:
      124 died and 227 had declines in activities of daily living. There was a graded,
      statistically significant relation between level of education and poor functional
      recovery, regardless of impairment of activities of daily living at baseline.
      Poor functional recovery was more common in subjects with baseline impairment
      (50% [147/296]) than in those without baseline impairment (36% [204/566]).
      Independent predictors of poor functional recovery were low education, cognitive
      impairment, lack of social support, poor self-rated health, and high comorbidity.
      Sequential addition of demographic, economic, functional, psychosocial, and
      clinical factors to low education only modestly affected the association between
      low education and poor functional recovery. CONCLUSION: Educational disadvantage
      impairs functional recovery after hospitalization in older persons.

PMID- 15501203
TI  - Sex- and age-related differences in the prognostic value of C-reactive protein in
      patients with angiographic coronary artery disease.
AB  - PURPOSE: To determine whether sex and age affect serum C-reactive protein level
      and its prognostic value in patients with coronary artery disease. METHODS: In a
      consecutive series of 2254 patients with angiographically defined coronary artery
      disease, baseline C-reactive protein and predictive value for incident death or
      nonfatal myocardial infarction by sex and age (<55 and > or =55 years) were
      compared. C-reactive protein levels were measured by fluorescence polarization
      immunoassay with use of a medium-sensitivity method. Patients were followed for a
      mean (+/-SD) of 3.1 +/- 2.2 years. Comparisons used ln-transformed C-reactive
      protein and linear and time-to-event regression analyses, adjusting for
      confounders. RESULTS: Overall, women had higher geometric mean C-reactive protein
      levels than did men (1.47 vs. 1.30 mg/dL, P <0.001), even after adjustment for
      age, hyperlipidemia, diabetes, prior myocardial infarction, body mass index, and
      heart failure (P = 0.002). High C-reactive protein levels were associated with
      increased mortality or myocardial infarction among men (adjusted hazard ratio
      [HR] = 1.9; 95% confidence interval [CI]: 1.5 to 2.3) but not among women (HR =
      1.0; 95% CI: 0.69 to 1.4). Among patients aged <55 years, C-reactive protein
      level was similarly predictive in men and women (HR = 2.2 vs. 2.7), whereas in
      patients > or =55 years of age, it remained predictive for men (HR = 1.8; 95% CI:
      1.5 to 2.3) but not women (HR = 0.93; 95% CI: 0.63 to 1.4). CONCLUSION: We found
      that the prognostic value of C-reactive protein in coronary artery disease
      patients varied by sex and age. This sex-age interaction may have important
      implications for C-reactive protein-based secondary risk assessment and requires
      further investigation.

PMID- 15501204
TI  - Pulmonary hypertension in sickle cell disease.
AB  - BACKGROUND: Recurrent vaso-occlusive episodes lead to progressive end-organ
      damage in patients with sickle cell disease. We sought to determine the
      prevalence of pulmonary hypertension in adult patients with sickle cell disease
      and to identify factors associated with this life-threatening complication.
      METHODS: Sixty patients (> or =18 years of age; mean [+/- SD] age, 37 +/- 13
      years) followed at a University Medical Center were evaluated. They were selected
      by a systematic sampling of patients presenting to the clinic for routine follow
      up visits. All enrolled subjects underwent a clinical examination, Doppler
      echocardiography, pulmonary function tests, and hematologic tests during a single
      visit. Pulmonary hypertension was defined using an age- and body mass index
      adjusted nomogram. RESULTS: The prevalence of pulmonary hypertension was 30%
      (18/60). Ten patients had mild pulmonary hypertension (up to 44 mm Hg), 5 had
      moderate pulmonary hypertension (45 to 74 mm Hg), and 2 had severe pulmonary
      hypertension (> or =75 mm Hg). In a logistic regression model, both lower fetal
      hemoglobin level and lower systolic blood pressure were associated with the
      presence of pulmonary hypertension. CONCLUSION: We found that the prevalence of
      pulmonary hypertension in adult patients with sickle cell disease was
      substantial, particularly in those with lower levels of fetal hemoglobin and
      lower systolic blood pressure.

PMID- 15501205
TI  - The net transfer of transplant organs across race, sex, age, and income.
AB  - PURPOSE: To determine how sociodemographic characteristics influence both access
      to transplantation and organ donation. METHODS: For all transplants in the United
      States from 1996 to 2001, donor-recipient pairs were categorized as white-white,
      white-black, black-white, or black-black. The difference in the percentage of
      white-black versus black-white pairs was calculated as a measure of the net
      transfer of organs from one racial group to another. A similar approach was used
      to examine the net transfer of organs across other sociodemographic categories.
      RESULTS: Among cadaveric renal transplants, 66% of donor-recipient pairs were
      white-white, 23% were white-black, 5% were black-white, and 6% were black-black.
      Thus, there was an 18% net transfer of organs from white donors to black
      recipients (23% minus 5%). Among living donor transplants involving spouses,
      there was a 36% net transfer from wives to husbands. Among all cadaveric
      transplants, there was a 36% to 68% net transfer from younger donors to older
      recipients. Among cadaveric nonrenal transplants, there was a 7% to 18% net
      transfer from lower-income donors to higher-income recipients. CONCLUSION: The
      sociodemographic characteristics of persons who donate organs and those who
      benefit from organ transplantation differ markedly. Efforts to improve access and
      increase donation should address these differences.

PMID- 15501206
TI  - Usefulness of clinical prediction rules for the diagnosis of venous
      thromboembolism: a systematic review.
AB  - PURPOSE: To summarize the evidence on the predictive value of clinical prediction
      rules for the diagnosis of venous thromboembolism. METHODS: We selected all
      studies in the English literature in which a clinical prediction rule was
      prospectively validated against a reference standard, and calculated likelihood
      ratios, predictive values, and the area under the receiver operating
      characteristic (ROC) curve for each prediction rule. RESULTS: Twenty-three
      studies met our eligibility criteria: 17 evaluated prediction rules for the
      diagnosis of deep venous thrombosis and six evaluated rules for pulmonary
      embolism. The most frequently evaluated prediction rule for deep vein thrombosis
      was the Wells rule, which had median positive likelihood ratios of 6.62 for
      patients with a high pretest probability, 1 for moderate pretest probability, and
      0.22 for low pretest probability. The median area under the ROC curve was 0.82.
      Addition of the D-dimer test to the prediction rule increased the median area
      under the curve to 0.90. The Wells prediction rule was the most commonly studied
      for pulmonary embolus and had median positive likelihood ratios of 6.75 for those
      with high pretest probability, 1.82 for moderate pretest probability, and 0.13
      for low pretest probability. The median area under the ROC curve was 0.82.
      CONCLUSION: The Wells prediction rule is useful in identifying patients at low
      risk of being diagnosed with venous thromboembolism. The addition of a rapid
      latex D-dimer assay improved the overall performance of the prediction rule.

PMID- 15501207
TI  - Arrhythmogenic right ventricular cardiomyopathy: clinical presentation,
      diagnosis, and management.
AB  - Arrhythmogenic right ventricular cardiomyopathy, also known as right ventricular
      dysplasia, is a genetically determined heart muscle disease associated with
      arrhythmia, heart failure, and sudden death. Autosomal dominant inheritance is
      typical. The identification of causative mutations in cell adhesion proteins has
      shed new light on its pathogenesis. Fibrofatty replacement of the myocardium, the
      hallmark pathologic feature, may be a response to injury caused by myocyte
      detachment. Sudden death is often the first manifestation in probands,
      emphasizing the importance of evaluating asymptomatic relatives for the disease.
      Standardized guidelines facilitate the clinical diagnosis of right ventricular
      dysplasia. However, familial studies have highlighted the need to broaden the
      diagnostic criteria, which are highly specific but lack sensitivity for early
      disease. Modifications have been proposed for the diagnosis of right ventricular
      dysplasia in relatives. Early right ventricular dysplasia is characterized by a
      "concealed phase" in which electrocardiographic and imaging abnormalities are
      often absent, but patients may nonetheless be at risk for arrhythmic events.
      Detection at this stage remains a clinical challenge, underscoring the potential
      value of mutation analysis in identifying affected persons. Serial evaluation of
      patients with suspected right ventricular dysplasia is recommended as clinical
      features may develop during the follow-up period. The onset of symptoms such as
      palpitation or syncope may herald an active phase of a previously quiescent
      disease, during which patients are at increased risk for sudden death. Greater
      awareness of right ventricular dysplasia among physicians and judicious use of
      implantable cardioverter-defibrillators may help to prevent unnecessary deaths.

PMID- 15501208
TI  - Disturbed metabolism of remnant lipoproteins in patients with subclinical
      hypothyroidism.

PMID- 15501209
TI  - Cases from the Osler Medical Service at Johns Hopkins University.
AB  - PRESENTING FEATURES: An 85-year-old black woman presented to the Osler Medical
      Service complaining of a pruritic, erythematous scaly rash that was on her right
      thigh and abdomen and that had been worsening over the prior 3 months. She also
      complained of increasing fatigue, decreased exercise tolerance, and a 5-lbs
      weight loss. There was no orthopnea, paroxysmal nocturnal dyspnea, fevers,
      chills, or night sweats. She denied recent travel and exposures to or contact
      with ill people. Her past medical history was unremarkable. There was no history
      of eczema, atopy, or dermatologic conditions. Her only medication was a baby
      aspirin taken daily. On physical examination, she was afebrile, her blood
      pressure was 110/72 mm Hg, and her pulse was 82 beats per minute with a room air
      oxygen saturation 98%. She was mildly obese but in no apparent distress. She had
      1-cm anterior cervical lymphadenopathy bilaterally and a 1-cm left axillary lymph
      node. Cardiovascular and chest examination was unremarkable. Her abdomen was soft
      and nontender, with a faint, erythematous rash that was mildly scaly but
      nontender in her abdominal skin fold. Her right thigh showed a large erythematous
      area, approximately 15 x 20 cm, which was scaly with multiple areas of
      discoloration (Figure 1). There was no palpable mass. She had slight edema in her
      right leg. Her left thigh was normal. Neurologic examination was nonfocal.
      Laboratory studies were notable for a white blood cell count of 17,000
      cells/microL, with a differential of 46% lymphocytes. The absolute lymphocyte
      count was 8000 cells/microL. Hematocrit was 28%. Platelet count was normal. A
      comprehensive metabolic panel was normal. A peripheral blood smear (Figure 2)
      showed numerous atypical lymphocytes with cerebriform nuclei. Peripheral blood
      flow cytometry showed the presence of a clonal population of T cells that
      expressed CD4 and CD5 but showed a loss of CD7. What is the diagnosis?

PMID- 15501210
TI  - Utilization management: a bad review.

PMID- 15501211
TI  - Overreliance on computerized algorithms to interpret electrocardiograms.

PMID- 15501212
TI  - Confounding factors affecting association of antihypertensive medications and
      pulse pressure.

PMID- 15501214
TI  - Rheumatoid arthritis and heart failure.

PMID- 15501215
TI  - Prognostic importance of lymphopenia in West Nile encephalitis.

PMID- 15501216
TI  - Requirement for hypertension and hyperlipidemia medication in U.S. and Japanese
      patients with diabetes.

PMID- 15501217
TI  - The Clerkship Directors in Internal Medicine's agenda for advancing medical
      student education in internal medicine.

PMID- 15501218
TI  - Conserved and divergent paths that regulate self-renewal in mouse and human
      embryonic stem cells.
AB  - The past few years have seen remarkable progress in our understanding of
      embryonic stem cell (ES cell) biology. The necessity of examining human ES cells
      in culture, coupled with the wealth of genomic data and the multiplicity of cell
      lines available, has enabled researchers to identify critical conserved pathways
      regulating self-renewal and identify markers that tightly correlate with the ES
      cell state. Comparison across species has suggested additional pathways likely to
      be important in long-term self-renewal of ES cells including heterochronic genes,
      microRNAs, genes involved in telomeric regulation, and polycomb repressors. In
      this review, we have discussed information on molecules known to be important in
      ES cell self-renewal or blastocyst development and highlighted known differences
      between mouse and human ES cells. We suggest that several additional pathways
      required for self-renewal remain to be discovered and these likely include genes
      involved in antisense regulation, microRNAs, as well as additional global
      repressive pathways and novel genes. We suggest that cross species comparisons
      using large-scale genomic analysis tools are likely to reveal conserved and
      divergent paths required for ES cell self-renewal and will allow us to derive ES
      lines from species and strains where this has been difficult.

PMID- 15501219
TI  - Muscle satellite cell-specific genes identified by genetic profiling of MyoD
      deficient myogenic cell.
AB  - Satellite cells are committed myogenic progenitors that give rise to
      proliferating myoblasts during postnatal growth and repair of skeletal muscle. To
      identify genes expressed at different developmental stages in the satellite cell
      myogenic program, representational difference analysis of cDNAs was employed to
      identify more than 50 unique mRNAs expressed in wild-type myoblasts and MyoD-/-
      myogenic cells. Novel expression patterns for several genes, such as Pax7, Asb5,
      IgSF4, and Hoxc10, were identified that were expressed in both quiescent and
      activated satellite cells. Several previously uncharacterized genes that
      represent putative MyoD target genes were also identified, including Pw1, Dapk2,
      Sytl2, and NLRR1. Importantly, many genes such as IgSF4, Neuritin, and Klra18
      that were expressed exclusively in MyoD-/- myoblasts were also expressed by
      satellite cells in undamaged muscle in vivo but were not expressed by primary
      myoblasts. These data are consistent with a biological role for activated
      satellite cells that induce Myf5 but not MyoD. Lastly, additional endothelial and
      hematopoietic markers were identified supporting a nonsomitic developmental
      origin of the satellite cell myogenic lineage.

PMID- 15501220
TI  - Transient apical polarization of Gliotactin and Coracle is required for parallel
      alignment of wing hairs in Drosophila.
AB  - In Drosophila, wing hairs are aligned in a distally oriented, parallel array. The
      frizzled pathway determines proximal-distal cell polarity in the wing; however,
      in frizzled pathway mutants, wing hairs remain parallel. How wing hairs align has
      not been determined. We have demonstrated a novel role for the septate junction
      proteins Gliotactin (Gli) and Coracle (Cora) in this process. Prior to prehair
      extension, Gli and Cora were restricted to basolateral membranes. During pupal
      prehair development, Gli and Cora transiently formed apical ribbons oriented from
      the distal wing tip to the proximal hinge. These ribbons were aligned beneath
      prehair bases and persisted for several hours. During this time, Gli was lost
      entirely from the basolateral domain. A Gliotactin mutation altered the apical
      polarization Gli and Cora and induced defects in hair alignment in pupal and
      adult stages. Genetic and cell biological assays demonstrated that Gli and Cora
      function to align hairs independently of frizzled. Taken together, our results
      indicate that Gli and Cora function as the first-identified members of a long
      predicted, frizzled-independent parallel alignment mechanism. We propose a model
      whereby the apical polarization of Gli and Cora functions to stabilize and align
      prehairs relative to anterior-posterior cell boundaries during pupal wing
      development.

PMID- 15501221
TI  - The role of Emx2 during scapula formation.
AB  - The scapula is subdivided into head, collum, and blade. Due to the expression
      pattern of Emx2 and the absence of the scapula blade in Emx2 knockout mice, it
      has been suggested that Emx2 is involved in the formation of the scapula.
      Micromanipulation experiments revealed that ectoderm ablation over the somites
      does not affect Emx2 expression but inhibits the formation of the scapula blade
      indicating that Emx2 is not sufficient to induce scapula blade formation.
      Furthermore, we show that the formation of the scapula head is dependent, scapula
      blade formation independent of FGFR-1-mediated signaling. Overexpression of Emx2
      does not influence scapula blade formation but leads to the development of an
      additional posterior digit in the anterior border of the limb. Taken together,
      the data presented implicate that Emx2 expression is necessary but not sufficient
      for the development of the scapula blade. It is not a marker for scapula
      development but rather provides positional information along the proximodistal
      and anterior-posterior limb axes, whereas the specificity of the developing
      skeletal elements is determined by the concerted interaction of Emx2 with other
      factors.

PMID- 15501222
TI  - A balance between the anti-apoptotic activity of Slug and the apoptotic activity
      of msx1 is required for the proper development of the neural crest.
AB  - We have studied the pattern of programmed cell death in the neural crest and
      analyzed how it is controlled by the activity of the transcription factors Slug
      and msx1. Our results indicate that apoptosis is more prevalent in the neural
      folds than in the rest of the neural ectoderm. Through gain- and loss-of-function
      experiments with inducible forms of both Slug and msx1 genes, we showed that Slug
      acts as an anti-apoptotic factor whereas msx1 promotes cell death, either in the
      neural folds of the whole embryos, in isolated or induced neural crest and in
      animal cap assays. The protective effect of expressing Slug can be reversed by
      expressing the apoptotic factor Bax, while the apoptosis promoted by msx1 can be
      abolished by expressing the Xenopus homologue of Bcl2 (XR11). Furthermore, we
      show that Slug and msx1 control the transcription of XR11 and several caspases
      required for programmed cell death. In addition, expression of Bax or Bcl2,
      produced similar effects on the survival of the neural crest and on the
      development of its derivatives to those produced by altering the activity of Slug
      or msx1. Finally, we show that in the neural crest, the region of the neural
      folds where Slug is expressed, cells undergo less apoptosis, than in the region
      where the msx1 gene is expressed, which correspond to cells adjacent to the
      neural crest. We show that the expression of Slug and msx1 controls cell death in
      certain areas of the neural folds, and we discuss how this equilibrium is
      necessary to generate sharp boundaries in the neural crest territory, and to
      precisely control cell number among neural crest derivatives.

PMID- 15501223
TI  - The sperm chemoattractant "allurin" is expressed and secreted from the Xenopus
      oviduct in a hormone-regulated manner.
AB  - Recently, we cloned and sequenced the cDNA of allurin, a sperm chemoattractant
      isolated from the jelly of Xenopus laevis eggs [Proc. Natl. Acad. Sci. U.S.A. 78
      (2001) 11205]. In this report, we demonstrate that allurin mRNA is expressed
      almost exclusively in the oviduct and that its expression is increased 2.5-fold
      by human chorionic gonadotropin over a 12-h period. Both dot blots and
      immunocytochemistry show that allurin is secreted from the upper two thirds of
      the oviduct that includes the pars recta and the proximal pars convoluta. Allurin
      appears to be deposited on the ciliated surfaces of luminal epithelial cells that
      come in direct contact with eggs as they move through the oviduct. Immune
      staining also demonstrates the presence of allurin in the serosal capsule of the
      oviduct. In contrast, allurin is not found within the tubular jelly-secreting
      glands or ducts that constitute a major portion of the oviduct wall. Therefore,
      we hypothesize that allurin is synthesized by nonciliated secretory cells in the
      luminal epithelium of the oviduct, is displayed on the ciliary layer and then
      mechanically mixed with jelly, and applied to eggs as they progress down the
      oviduct. This hypothesis is consistent with the fact that eggs progressing down
      the oviduct initially show evidence of allurin being incorporated into the J1
      layer. Subsequently, allurin within J1 diffuses outward to J3 and eggs stored in
      the uterus now demonstrate a J3 localization of this chemoattractant.

PMID- 15501224
TI  - BMP antagonism by Spemann's organizer regulates rostral-caudal fate of mesoderm.
AB  - Recent revisions to the Xenopus fate map challenge the interpretation of previous
      maps and current models of amphibian axial patterning (Lane, M.C., Smith, W.C.,
      1999. The origins of primitive blood in Xenopus: implications for axial
      patterning. Development 126 (3), 423-434.; Lane, M.C., Sheets, M.D., 2000.
      Designation of the anterior/posterior axis in pregastrula Xenopus laevis. Dev.
      Biol. 225, 37-58). We determined the rostralmost contributions to both dorsal and
      ventral mesoderm concomitantly from marginal zone progenitors in stage 6 embryos.
      Data reveal an unequivocal rostral-to-caudal progression of both dorsal and
      ventral mesoderm across the pre-gastrula axis historically called the dorsal
      ventral axis, and a dorsal-to-ventral progression from animal-to-vegetal in the
      marginal zone. These findings support the proposed revisions to the fate and axis
      orientation maps. Most importantly, these results raise questions about the role
      of the organizer grafts and organizer-derived BMP antagonists in the "induction"
      of secondary axes. We re-examine both phenomena, and find that organizer grafts
      and BMP antagonists evoke caudal-to-rostral mesodermal fate transformations, and
      not ventral-to-dorsal transformations as currently believed. We demonstrate that
      BMP antagonism evokes a second axis because it stimulates precocious mediolateral
      intercalation of caudal, dorsal mesoderm. The implications of these findings for
      models of organizer function in vertebrate axial patterning are discussed.

PMID- 15501225
TI  - Pax-7 up-regulation inhibits myogenesis and cell cycle progression in satellite
      cells: a potential mechanism for self-renewal.
AB  - Satellite cells are myogenic precursors responsible for skeletal muscle
      regeneration. Satellite cells are absent in the Pax-7-/- mouse, suggesting that
      this transcription factor is crucial for satellite cell specification [Seale, P.,
      Sabourin, L.A., Girgis-Gabardo, A., Mansouri, A., Gruss, P., Rudnicki, M.A.,
      2000. Pax7 is required for the specification of myogenic satellite cells. Cell
      102, 777-786]. Analysis of Pax-7 expression in activated satellite cells
      unexpectedly revealed substantial heterogeneity within individual clones. Further
      analyses show that Pax-7 and myogenin expression are mutually exclusive during
      differentiation, where Pax-7 appears to be up-regulated in cells that escape
      differentiation and exit the cell cycle, suggesting a regulatory relationship
      between these two transcription factors. Indeed, overexpression of Pax-7 down
      regulates MyoD, prevents myogenin induction, and blocks MyoD-induced myogenic
      conversion of 10T1/2 cells. Overexpression of Pax-7 also promotes cell cycle exit
      even in proliferation conditions. Together, these results suggest that Pax-7 may
      play a crucial role in allowing activated satellite cells to reacquire a
      quiescent, undifferentiated state. These data support the concept that satellite
      cell self-renewal may be a primary mechanism for replenishment of the satellite
      cell compartment during skeletal muscle regeneration.

PMID- 15501226
TI  - Analysis of forkhead and snail expression reveals epithelial-mesenchymal
      transitions during embryonic and larval development of Nematostella vectensis.
AB  - The winged helix transcription factor Forkhead and the zinc finger transcription
      factor Snail are crucially involved in germ layer formation in Bilateria. Here,
      we isolated and characterized a homolog of forkhead/HNF3 (FoxA/group 1) and of
      snail from a diploblast, the sea anemone Nematostella vectensis. We show that
      Nematostella forkhead expression starts during late Blastula stage in a ring of
      cells that demarcate the blastopore margin during early gastrulation, thereby
      marking the boundary between ectodermal and endodermal tissue. snail, by
      contrast, is expressed in a complementary pattern in the center of forkhead
      expressing cells marking the presumptive endodermal cells fated to ingress during
      gastrulation. In a significant portion of early gastrulating embryos, forkhead is
      expressed asymmetrically around the blastopore. While snail-expressing cells form
      the endodermal cell mass, forkhead marks the pharynx anlage throughout embryonic
      and larval development. In the primary polyp, forkhead remains expressed in the
      pharynx. The detailed analysis of forkhead and snail expression during
      Nematostella embryonic and larval development further suggests that endoderm
      formation results from epithelial invagination, mesenchymal immigration, and
      reorganization of the endodermal epithelial layer, that is, by epithelial
      mesenchymal transitions (EMT) in combination with extensive morphogenetic
      movements. snail also governs EMT at different processes during embryonic
      development in Bilateria. Our data indicate that the function of snail in
      Diploblasts is to regulate motility and cell adhesion, supporting that the
      triggering of changes in cell behavior is the ancestral role of snail in Metazoa.

PMID- 15501227
TI  - Nodal inhibits differentiation of human embryonic stem cells along the
      neuroectodermal default pathway.
AB  - Genetic studies in fish, amphibia, and mice have shown that deficiency of Nodal
      signaling blocks differentiation into mesoderm and endoderm. Thus, Nodal is
      considered as a major inducer of mesendoderm during gastrulation. On this basis,
      Nodal is a candidate for controlling differentiation of pluripotent human
      embryonic stem cells (hESCs) into tissue lineages with potential clinical value.
      We have investigated the effect of Nodal, both as a recombinant protein and as a
      constitutively expressed transgene, on differentiation of hESCs. When control
      hESCs were grown in chemically defined medium, their expression of markers of
      pluripotency progressively decreased, while expression of neuroectoderm markers
      was strongly upregulated, thus revealing a neuroectodermal default mechanism for
      differentiation in this system. hESCs cultured in recombinant Nodal, by contrast,
      showed prolonged expression of pluripotency marker genes and reduced induction of
      neuroectoderm markers. These Nodal effects were accentuated in hESCs expressing a
      Nodal transgene, with striking morphogenetic consequences. Nodal-expressing hESCs
      developing as embryoid bodies contained an outer layer of visceral endoderm-like
      cells surrounding an inner layer of epiblast-like cells, each layer having
      distinct gene expression patterns. Markers of neuroectoderm were not upregulated
      during development of Nodal-expressing embryoid bodies, nor was there induction
      of markers for definitive mesoderm or endoderm differentiation. Moreover, the
      inner layer expressed markers of pluripotency, characteristic of undifferentiated
      hESCs and of epiblast in mouse embryos. These results could be accounted for by
      an inhibitory effect of Nodal-induced visceral endoderm on pluripotent cell
      differentiation into mesoderm and endoderm, with a concomitant inhibition of
      neuroectoderm differentiation by Nodal itself. There could also be a direct
      effect of Nodal in the maintenance of pluripotency. In summary, analysis of the
      Nodal-expressing phenotype suggests a function for the transforming growth factor
      beta (TGF-beta) growth factor superfamily in pluripotency and in early cell fate
      decisions leading to primary tissue layers during in vitro development of
      pluripotent human stem cells. The effects of Nodal on early differentiation
      illustrate how hESCs can augment mouse embryos as a model for analyzing
      mechanisms of early mammalian development.

PMID- 15501228
TI  - Mef2c is activated directly by Ets transcription factors through an
      evolutionarily conserved endothelial cell-specific enhancer.
AB  - Members of the Myocyte Enhancer Factor 2 (MEF2) family of transcription factors
      play key roles in the development and differentiation of numerous cell types
      during mammalian development, including the vascular endothelium. Mef2c is
      expressed very early in the development of the endothelium, and genetic studies
      in mice have demonstrated that mef2c is required for vascular development.
      However, the transcriptional pathways involving MEF2C during endothelial cell
      development have not been defined. As a first step towards identifying the
      transcriptional factors upstream of MEF2C in the vascular endothelium, we
      screened for transcriptional enhancers from the mouse mef2c gene that regulate
      vascular expression in vivo. In this study, we identified a transcriptional
      enhancer from the mouse mef2c gene sufficient to direct expression to the
      vascular endothelium in transgenic embryos. This enhancer is active in
      endothelial cells within the developing vascular system from very early stages in
      vasculogenesis, and the enhancer remains robustly active in the vascular
      endothelium during embryogenesis and in adulthood. This mef2c endothelial cell
      enhancer contains four perfect consensus Ets transcription factor binding sites
      that are efficiently bound by Ets-1 protein in vitro and are required for
      enhancer function in transgenic embryos. Thus, these studies identify mef2c as a
      direct transcriptional target of Ets factors via an evolutionarily conserved
      transcriptional enhancer and establish a direct link between these two early
      regulators of vascular gene expression during endothelial cell development in
      vivo.

PMID- 15501229
TI  - Different combinations of gap repressors for common stripes in Anopheles and
      Drosophila embryos.
AB  - Drosophila segmentation is governed by a well-defined gene regulation network.
      The evolution of this network was investigated by examining the expression
      profiles of a complete set of segmentation genes in the early embryos of the
      mosquito, Anopheles gambiae. There are numerous differences in the expression
      profiles as compared with Drosophila. The germline determinant Oskar is expressed
      in both the anterior and posterior poles of Anopheles embryos but is strictly
      localized within the posterior plasm of Drosophila. The gap genes hunchback and
      giant display inverted patterns of expression in posterior regions of Anopheles
      embryos, while tailless exhibits an expanded pattern as compared with Drosophila.
      These observations suggest that the segmentation network has undergone
      considerable evolutionary change in the dipterans and that similar patterns of
      pair-rule gene expression can be obtained with different combinations of gap
      repressors. We discuss the evolution of separate stripe enhancers in the eve loci
      of different dipterans.

PMID- 15501230
TI  - Major chromatin remodeling in the germinal vesicle (GV) of mammalian oocytes is
      dispensable for global transcriptional silencing but required for centromeric
      heterochromatin function.
AB  - Global silencing of transcriptional activity in the oocyte genome occurs just
      before the resumption of meiosis and is a crucial developmental transition at the
      culmination of oogenesis. Transcriptionally quiescent oocytes rely on stored
      maternal transcripts to sustain the completion of meiosis, fertilization, and
      early embryonic cleavage stages. Thus, the timing of silencing is key for
      successful embryo development. Yet, the cellular and molecular pathways
      coordinating dynamic changes in large-scale chromatin structure with the onset of
      transcriptional repression are poorly understood. Here, oocytes obtained from
      nucleoplasmin 2 knockout (Npm2-/-) mice were used to investigate the relationship
      between transcriptional repression and chromatin remodeling in the germinal
      vesicle (GV) of mammalian oocytes. Although temporally linked, global silencing
      of transcription and chromatin remodeling in the oocyte genome can be
      experimentally dissociated and therefore must be regulated through distinct
      pathways. Detection of centromeric heterochromatin DNA sequences with a mouse pan
      centromeric chromosome paint revealed that most centromeres are found in close
      apposition with the nucleolus in transcriptionally quiescent oocytes and
      therefore constitute an important component of the perinucleolar heterochromatin
      rim or karyosphere. Pharmacological inhibition of histone deacetylases (HDACs)
      with trichostatin A (TSA) revealed that HDACs are essential for large-scale
      chromatin remodeling in the GV. Importantly, the specialized nuclear architecture
      acquired upon transcriptional repression is essential for meiotic progression as
      interference with global deacetylation and partial disruption of the karyosphere
      resulted in a dramatic increase in the proportion of oocytes exhibiting abnormal
      meiotic chromosome and spindle configuration. These results indicate that the
      unique chromatin remodeling mechanism in oocytes may be specifically related to
      meiotic cell division in female mammals.

PMID- 15501231
TI  - An enhancer trap in the ascidian Ciona intestinalis identifies enhancers of its
      Musashi orthologous gene.
AB  - The enhancer trap technique, established in Drosophila melanogaster, is a very
      sophisticated tool. Despite its usefulness, however, there have been very few
      reports on enhancer traps in other animals. The ascidian Ciona intestinalis, a
      splendid experimental system for developmental biology, provides good material
      for developmental genetics. Recently, germline transgenesis of C. intestinalis
      has been achieved using the Tc1/mariner superfamily transposon Minos. During the
      course of that study, one Minos insertion line that showed a different GFP
      expression pattern from other lines was isolated. One fascinating possibility is
      that an enhancer trap event occurred in this line. Here we show that a Minos
      insertion in the Ci-Musashi gene was responsible for the altered GFP expression.
      Ci-Musashi showed a similar expression pattern to GFP. In addition, introns of Ci
      Musashi have enhancer activity that can alter the expression pattern of nearby
      genes to resemble that of GFP in this line. These results clearly demonstrate
      that an enhancer trap event that entrapped enhancers of Ci-Musashi occurred in C.
      intestinalis.

PMID- 15501233
TI  - The theory of three-dimensional image formation in a light microscope.

PMID- 15501232
TI  - Gene expression profiling of the developing Drosophila CNS midline cells.
AB  - The Drosophila CNS midline cells constitute a specialized set of interneurons,
      motorneurons, and glia. The utility of the CNS midline cells as a neurogenomic
      system to study CNS development derives from the ability to easily identify CNS
      midline-expressed genes. For this study, we used a variety of sources to identify
      281 putative midline-expressed genes, including enhancer trap lines, microarray
      data, published accounts, and the Berkeley Drosophila Genome Project (BDGP) gene
      expression data. For each gene, we analyzed expression at all stages of embryonic
      CNS development and categorized expression patterns with regard to specific
      midline cell types. Of the 281 candidates, we identified 224 midline-expressed
      genes, which include transcription factors, signaling proteins, and transposable
      elements. We find that 58 genes are expressed in mesectodermal precursor cells,
      138 in midline primordium cells, and 143 in mature midline cells--50 in midline
      glia, 106 in midline neurons. Additionally, we identified 27 genes expressed in
      glial and mesodermal cells associated with the midline cells. This work provides
      the basis for future research that will generate a complete cellular and
      molecular map of CNS midline development, thus allowing for detailed genetic and
      molecular studies of neuronal and glial development and function.

PMID- 15501234
TI  - Bone marrow mononuclear cell transplantation into heart elevates the expression
      of angiogenic factors.
AB  - The expression of angiogenic factors was measured to elucidate the mechanism of
      angiogenesis after bone marrow stem cells transplantation. The left anterior
      descending coronary (LAD) artery was ligated in male Lewis rats to induce an
      acute myocardial infarction (AMI); of which, some rats received bone marrow
      mononuclear cells transplantation (BMT). The expression of cytokines and their
      receptors was assessed by RT-PCR. The expression of c-met was upregulated in the
      AMI animals and was further increased when the animals received BMT (P < 0.01).
      The other cytokines and their receptors remained unchanged after BMT compared
      with AMI samples. Normal bone marrow mononuclear cells have higher expression
      level of hepatocyte growth factor (HGF) than those in normal hearts. In
      conclusion, BMT could increase the expression of c-met. Not all angiogenic
      cytokines and their receptors were upregulated after BMT. The higher expression
      of hepatocyte growth factor in bone marrow may contribute to the upregulation of
      c-met.

PMID- 15501235
TI  - Angiogenic synergy of bFGF and VEGF is antagonized by Angiopoietin-2 in a
      modified in vivo Matrigel assay.
AB  - A murine modification of the Matrigel chamber assay originally developed for use
      on rats is presented. This modified assay permits improved quantification due to
      subcutaneous Matrigel implants of constant shape and volume. We have
      quantitatively assessed the angiogenic potential of the growth factors basic
      fibroblast growth factor (bFGF), VEGF, and Angiopoietin-2 (Ang-2) with special
      emphasis on their mutual interactions. A reproducible dose-response relationship
      for bFGF was established for doses between 150 and 1000 ng per chamber, whereas
      VEGF did not display angiogenic activity on its own in the tested dose of up to
      200 ng per chamber. Conversely, we found a strong synergistic action of bFGF and
      VEGF when combined in a 3:1 ratio. Two other combinations (ratios) with greater
      VEGF doses were also tested, but the synergistic effect was only observed when 50
      ng of VEGF was added to 150 ng per chamber of bFGF. This synergistic effect of
      bFGF and VEGF was significantly reduced by further addition of 100 ng
      Angiopoietin-2. Inhibition of the response to bFGF and VEGF was confirmed by in
      vitro EC migration experiments, which, together with our in vivo results,
      indicates that Ang-2 may target chemotactic responses to bFGF and VEGF in vivo.

PMID- 15501236
TI  - Matrix-bound sixth Ig-like domain of cell adhesion molecule L1 acts as an
      angiogenic factor by ligating alphavbeta3-integrin and activating VEGF-R2.
AB  - Angiogenic signals can be matrix attached or freely diffusible. Here, the sixth
      Ig-like domain of L1 (L1Ig6), a ligand for alphavbeta3-integrin, was
      investigated. This domain was expressed as a fusion protein having a substrate
      sequence for factor XIII to enable covalent binding into three-dimensional fibrin
      matrices. Matrix-bound L1Ig6 induced endothelial cell (EC) process extension in
      vitro, which was associated with ligation and phosphorylation of alphavbeta3
      integrin. VEGF-R2 and alphavbeta3 were observed to co-associate after stimulation
      with either L1Ig6 or VEGF-A165, whereas no co-association with bFGF-R was
      observed. Furthermore, VEGF-R2 was tyrosine phosphorylated after stimulation with
      L1Ig6, even in the absence of exogenous VEGF-A165, indicating close cooperation
      between VEGF-R2 and alphavbeta3. Angiogenesis was investigated in vivo by
      stimulating chicken chorioallantoic membranes (CAMs) with L1Ig6-modified matrices
      with or without co-incorporation of VEGF-A165 or bFGF. Matrix-immobilized L1Ig6
      induced angiogenesis to a similar degree as VEGF-A165; co-stimulation with bFGF
      increased vascular branching, whereas VEGF-A165 did not. Matrix-immobilized L1Ig6
      induced up-regulation of alphav in CAMs by a similar degree as stimulation with
      VEGF-A165, and this up-regulation was increased further by co-stimulation with
      matrix-bound L1Ig6 and VEGF-A165. alpha5 and beta1 levels were not increased. The
      similarity of action of matrix-bound L1Ig6 and soluble VEGF-A165 indicate a close
      link between specific ligation of alphavbeta3-integrin and VEGF-R2 and suggest
      the possible use of matrix-bound L1Ig6 in local therapeutic angiogenesis.

PMID- 15501237
TI  - A murine model of ex vivo angiogenesis using aortic disks grown in fibrin clot.
AB  - The rat aortic ring model is well utilized for evaluation of angiogenesis. We
      report here an alternative assay employing an ex vivo mouse aorta angiogenesis
      model that can be extensively manipulated and serially evaluated using digital
      assisted image analysis. Mouse aortas were harvested, cut into 2-mm disks, and
      cultured in fibrin matrix with growth media. Radial vascular outgrowths arose
      from the cut edge of the aortic disk and were digitally photographed and serially
      quantified. A variety of culture conditions were evaluated to determine their
      ability to alter angiogenesis in this model. Vessel outgrowth became apparent on
      day 3 and continued through day 10 with linear growth occurring between days 3
      and 6. Increasing concentrations of serum from 0% to 40% resulted in stimulation
      of angiogenesis after day 3. Suramin and endostatin dramatically inhibited
      angiogenesis, which was more profound when applied at day 0 than when linear
      growth could be identified (day 3). Cells isolated from vessel outgrowths were
      predominantly endothelial in origin by immunocytochemistry and FACS analysis. We
      demonstrate that angiogenesis in an ex vivo murine model can be easily quantified
      using digital image analysis, responds appropriately to stimulation and
      inhibition, and exhibits differential results based on time of inhibitor
      administration. Antiangiogenic agents may be most effective if administered
      before development of accelerated vessel growth.

PMID- 15501238
TI  - A 3D numerical study of the effect of channel height on leukocyte deformation and
      adhesion in parallel-plate flow chambers.
AB  - The effect of channel height on leukocyte adhesion to a lower plate in a parallel
      plate flow chamber is studied by direct numerical simulations in three
      dimensions. The numerical model takes into account deformability and
      viscoelasticity of the leukocyte, membrane ruffles (microvilli), and the presence
      of mechanically different regions inside the cell (nucleus and cytoplasm).
      Leukocyte adhesion is assumed to be mediated by interactions of adhesion
      molecules on the tips of microvilli with their counterparts on the lower plate.
      Results of this study indicate that an adherent leukocyte experiences much less
      drag than a rigid sphere due to its deformation and transient stress growth.
      While overall leukocyte deformation is modest at shear stresses encountered in
      the microcirculation, deformation in the contact region is significant. At fixed
      wall shear stress, the contact area of the cell membrane with the substrate
      increases with increasing the ratio of cell diameter to channel height, leading
      to greater adhesion. This suggests that in vitro flow chamber studies typically
      underestimate leukocyte adhesion that occurs in the microcirculation.

PMID- 15501239
TI  - Laser Doppler anemometry distinguishes primary Raynaud phenomenon from VWF
      syndrome.
AB  - OBJECTIVES: We evaluated two microcirculatory function-tests, the Laser Doppler
      (LD)-Anemometry and the Laser Doppler Imager (LDI)-Flowmetry in their value to
      further elucidate functional behavior of the "Vibration-induced white finger
      syndrome" (VWF) and to distinguish between Raynaud's phenomenon (RP) of
      idiopathic or vibration origin. PARTICIPANTS AND METHODS: Ninety-four patients,
      suffering from RP were studied (78 patients with primary RP and 16 patients with
      VWF). Measurement of blood cell velocity (BCV) before and after provocation was
      obtained by nailfold capillary microscopy and an included Laser detector
      ("Anemometry"). Digital blood flux was recorded by LDI-Flowmetry during a
      standardized cooling and rewarming thermal challenge. RESULTS: "Time to peak" of
      BCV, a measure of maximal reactive hyperemia was longer in VWF in comparison to
      primary RP (30.37 versus 19.29 sec P < 0.02), respectively. CONCLUSION: Based on
      the fact, that prolongation of reactive hyperemia, an indicator of impaired
      endothelium-dependent vasodilation is also frequently found in peripheral
      arterial occlusive disease, it is hypothesized that VWF is not only a
      microcirculatory vasospastic disorder, but may also be related to
      atherosclerosis. Anemometry, in association with an appropriate provocation-test,
      could represent a useful non-invasive method for objectifying diagnosis of VWF in
      patients with RP.

PMID- 15501240
TI  - Pericyte adhesion and growth onto polyhydroxymethylsiloxane surfaces
      nanostructured by plasma treatment and ion irradiation.
AB  - The study deals with the adhesion and proliferation of bovine retina pericytes
      onto surfaces of poly(hydroxymethylsiloxane) (PHMS) modified either by cold
      plasma or by low-energy ion beams. The surface treatment was able to convert the
      original polymer matrix into SiO2-like phases for O2-plasma or ion-mixed
      SiCxOy(Hz) phases for ion irradiation, respectively, with different modification
      levels of the surface free energy (SFE) and related surface wettability.
      Pericytes exhibited a negligible adhesion and proliferation onto untreated PHMS,
      an enhanced adhesion but not proliferation on plasma-treated PHMS, and great
      adhesion and proliferation to full confluence on ion-irradiated PHMS, as measured
      by X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), quartz
      crystal microbalance, and optical microscopy. On the other hand, the adhesion and
      proliferation of GP8.39 endothelial cells (EC), which are strongly associated
      with pericytes in microvasculature, were very scarce onto both untreated and
      surface-modified PHMS. The surface-selective pericytal response was related to
      changes of physicochemical properties of PHMS film, from hydrophobic/neutral
      towards hydrophilic/negatively charged polymer layers, as well as to short- and
      long-time events of cell-surface interaction. We propose that surface properties
      can mediate and modulate cell-polymer matrix adhesion through the establishment
      of stereospecific chemical interactions and/or electrostatic repulsion, which can
      also explain the different behavior of pericytes compared to EC.

PMID- 15501241
TI  - Direct chemotactic action of angiopoietin-1 on mesenchymal cells in the presence
      of VEGF.
AB  - Angiopoietin-1 (Ang1) and its receptor, Tie2, play an important role in
      angiogenesis and vessel maturation. We previously reported that overexpression of
      Ang1 in MCF7 xenograft tumors facilitated vessel stabilization by mural cells,
      and that cultured SMC express Tie2. Here, we investigated whether Ang1 directly
      acts as a chemoattractant on mural cells or their precursors. In a Matrigel plug
      assay, neither Ang1 nor VEGF alone induced angiogenesis but together stimulated
      infiltration of non-endothelial cells that were CD31-negative, vimentin-positive
      and also positive for VEGFR-1 and Tie2. While negative for smooth muscle actin,
      reactivity for desmin suggests that the cells are mural cell precursors. VEGF
      treatment of cultured smooth muscle cells (SMC) upregulated Tie2 and allowed for
      Ang1-mediated phosphorylation of Tie2 and the AKT serine-threonine kinase. The
      combination of Ang1 and VEGF stimulated SMC migration in a Boyden chamber-type
      assay. In the presence of VEGF, Tie2 is upregulated on mural cells, allowing for
      a migratory response to Ang1. These findings support the view that Ang1, in
      concert with VEGF, can act directly on mural cells or their precursors to
      facilitate their recruitment to new blood vessels. This action may play an
      important role in vascular stabilization.

PMID- 15501242
TI  - Hydrogen peroxide-induced alterations of tight junction proteins in bovine brain
      microvascular endothelial cells.
AB  - Occludin and zonular occludens (ZO)-1 in tight junctions (TJs) and actin play an
      important role in maintaining blood-brain barrier (BBB) endothelial ion and
      solute barriers. Malfunction of BBB by reactive oxygen species (ROS) has been
      attributed to the disruption of TJs. This study examined H2O2 effects on changes
      of paracellular permeability, actin, and TJ proteins (occludin and ZO-1) using
      primary culture of bovine brain microvessel endothelial cells. The BBB
      permeability, measured as transendothelial electrical resistance (TER), decreased
      in a dose- and time-dependent manner when treated with H2O2. Cytotoxicity test
      revealed that H2O2 did not cause cell death at 0.01, 0.1, and 1.0 mM H2O2. H2O2
      caused increased protein expression of occludin (1.17- to 1.29-fold) and actin
      (1.2- to 1.3-fold). ZO-1 maintained steady state levels of expression. H2O2
      caused rearrangement of occludin and ZO-1 at tight junctions and formation of
      actin stress fiber. Although ZO-1 did not show significant change in protein
      expression, permeability changes shown in the current study correlate with
      alterations in expression and localization of occludin, actin, and ZO-1. These
      data suggest that H2O2 induces increased paracellular permeability of BBB that is
      accompanied with redistribution of occludin and ZO-1 and increased protein
      expression of occludin and actin.

PMID- 15501243
TI  - Expression of placenta growth factor is regulated by both VEGF and hyperglycaemia
      via VEGFR-2.
AB  - Placenta growth factor (PlGF) has been implicated in both physiological and
      pathological angiogenesis; however, little is known about what regulates its
      expression. In this study, retinal microvascular endothelial cells and pericytes
      were exposed to varying concentrations of VEGF and glucose and PlGF expression
      measured by RT-PCR and Western blotting. Both PlGF mRNA and protein were observed
      in unstimulated microvascular endothelial cells with only weak expression in
      pericytes. In endothelial cells, VEGF (100 ng/ml) and glucose (15 mM) induced an
      increase in expression of PlGF at both the mRNA and protein level while no effect
      was observed for pericytes. The increase in PlGF expression could be totally
      abolished by blocking VEGFR-2, and in the case of glucose by neutralising VEGF.
      VEGF-stimulated PlGF expression was largely inhibited by PD 98059, an inhibitor
      of mitogen-activated protein kinase (MAPK) and partially by GF 109203X, an
      inhibitor of protein kinase C (PKC), indicating that VEGF up-regulates PlGF
      expression via the MAPK signalling pathway and partially through PKC. Taken
      together, our findings suggest that VEGF orchestrates the contribution of PlGF in
      angiogenesis via more than one intracellular pathway and that hyperglycaemia, as
      occurs in diabetes, is an important regulator of PlGF expression via VEGF up
      regulation.

PMID- 15501245
TI  - Interstitial flow differentially stimulates blood and lymphatic endothelial cell
      morphogenesis in vitro.
AB  - Whereas high shearing flows are known to induce endothelial cell remodeling, we
      show here that very low interstitial flow rates trigger endothelial cell
      morphogenesis in 3D cultures. Interstitial flow is a functionally critical
      component of the circulation, and we have recently observed that it plays a
      regulatory role in lymphangiogenesis; here we investigate interstitial flow as a
      powerful morphoregulatory stimulant. We exposed both lymphatic and blood
      endothelial cells (LECs and BECs) to interstitial flow in 3D collagen gels as
      well as simple shear flow in 2D monolayers. We found that under interstitial flow
      (average 10 microm/s for 6 days), both cell types underwent drastic morphologic
      changes from static conditions: LECs formed large vacuoles and long extensions,
      while BECs formed multicellular branched lumen-containing networks. Under planar
      shear (20 dyn/cm2 for 24 h), LECs downregulated their cell-cell adhesions
      compared to BECs but did not differ morphologically; both aligned with flow as
      expected. The significance of these findings is twofold: first, they identify an
      important role of interstitial flow for in vitro microvascular organization and
      stabilization, and second, they demonstrate for the first time notable
      differences between LEC and BEC response to the biophysical environment,
      reflecting some of their functional differences in vivo.

PMID- 15501244
TI  - Histamine reduces gap junctional communication of human tonsil high endothelial
      cells in culture.
AB  - The regulation of gap junctional communication by histamine was studied in
      primary cultures of human tonsil high endothelial cells (HUTECs). We evaluated
      intercellular communication, levels, state of phosphorylation, and cellular
      distribution of gap junction protein subunits, mainly connexin (Cx)43. Histamine
      induced a time-dependent reduction in dye coupling (Lucifer yellow) associated
      with reduction in connexin43 localized at cell-cell appositions
      (immunofluorescence), without changes in levels and phosphorylation state of
      connexin43 (immunoblots). These effects were prevented with chlorpheniramine, an
      H1 receptor blocker; indomethacin, a cyclooxygenase blocker; or GF109203X, a
      protein kinase C inhibitor. Treatment with phorbol myristate acetate, a protein
      kinase C activator, and 4bromo (4Br)-A23187, a calcium ionophore, mimicked the
      histamine-induced effects on dye coupling. 8Bromo-cAMP doubled the dye coupling
      extent and prevented the histamine-induced reduction in incidence of dye
      coupling. After 24-h histamine treatment, known to desensitize H1 receptors,
      reapplication of histamine increased cell coupling in a way prevented by
      ranitidine, an H2 receptor blocker. Thus, activation of H1 and H2 receptors,
      which increase intracellular levels of free Ca2+ and cAMP, respectively, may
      affect gap junctional communication in opposite ways. Stabilization of actin
      filaments with phalloidine diminished but did not totally prevent histamine
      induced cell shape changes and reduction in dye coupling. Hence, the histamine
      induced reduction in gap junctional communication between HUTEC is mediated by
      cytoskeleton-dependent and -independent mechanisms and might contribute to
      modulate endothelial function in lymphoid tissue.

PMID- 15501246
TI  - Mitochondria and blood supply of chicken skeletal muscle fibers in ontogenesis.
AB  - Skeletal muscles have been studied during ontogenesis to reveal morphological and
      functional parameters that at most influence the formation of muscles with
      different levels of oxygen consumption. Development of oxidative red
      gastrocnemius muscle (RGM) and glycolytic white pectoralis muscle (WPM) has been
      studied at a period from being 10-day-old chicken embryos until they become 6
      month-old chickens. By morphometry, we measured diameter, length, and numerical
      density of capillaries; muscle fibers diameter; as well as mitochondria's size,
      density, and volume fraction in muscle fibers. During the post-embryonic period,
      the blood flow was estimated by hydrogen clearance method. The data obtained were
      compared to previously published data on O2 consumption rate in fibers being at
      the same stages of ontogenesis [Microvasc. Res. 60 (2000) 168]. As shown,
      relationships between the parameters in the muscles studied appear at different
      ages. They are described by exponential equations with varying slopes. Beginning
      with the middle stages of embryogenesis, the clear dependency is seen in both
      types of muscles between O2 consumption rate in a fiber and summarized perimeter
      of mitochondria at a fiber section. Capillary bed during embryonal period is
      superfluous. The clear dependency between capillary-to-fiber number ratio and
      oxygen consumption in fibers becomes apparent in chickens only 10 days after
      birth, when the fiber diameter amounts to 20 microm. Since that period,
      redistribution of mitochondria toward the periphery of a fiber takes place, being
      especially pronounced in RGM. The regularities found between oxygen delivery and
      consumption systems enable to search for the leading factors of specialization of
      skeletal muscles in accordance with the level of oxidative metabolism. These
      factors may be used for calculation and numerical simulation of the parameters of
      oxygen transport in skeletal muscles.

PMID- 15501248
TI  - The permeability-reducing effects of prostacyclin and inhibition of Rho kinase do
      not counteract endotoxin-induced increase in permeability in cat skeletal muscle.
AB  - cAMP stimulation and Rho kinase inhibition are shown to decrease microvascular
      permeability during noninflammatory conditions, most likely by decreasing
      contractility of actomyosin filaments in the endothelial cell, but their effects
      on permeability during inflammatory conditions are not clarified. The objective
      of this in vivo study, performed on the autoperfused and denervated calf muscle
      of the cat, was therefore to evaluate to what extent cAMP stimulation and
      inhibition of Rho kinase reduce permeability at endotoxemia. Change in osmotic
      reflection coefficient for albumin was used as a measure of altered protein
      permeability and change in capillary filtration coefficient (CFC) as a measure of
      altered fluid permeability. After inducing a significant increase in protein and
      fluid permeability by infusion of lipopolysaccharide (LPS), we determined to what
      extent the increased permeability was decreased by the cAMP stimulator
      prostacyclin [1.0 ng/kg/min intravenously (iv)] or the Rho kinase inhibitor Y
      27632 [1.05 microg/ml plasma/h intraarterially (ia)]. These doses are known to
      decrease permeability under noninflammatory conditions. The reflection
      coefficient for albumin and CFC were determined before and during LPS, and during
      LPS plus prostacyclin (n = 6) or LPS plus Y-27632 (n = 6). The reflection
      coefficient was reduced by about 30% (P < 0.05) and CFC was increased by about
      25% (P < 0.05) by LPS, and these permeability parameters were not affected by
      prostacyclin or Y-27632. We conclude that cAMP stimulation and Rho kinase
      inhibition reduce permeability by other pathways and mechanisms than those by
      which permeability is increased during endotoxemia.

PMID- 15501247
TI  - Tissue-specific effect of estradiol on endothelial cell-dependent lymphocyte
      recruitment.
AB  - Estrogen profoundly affects onset and severity of many immune-mediated diseases.
      In our murine model of drug-induced autoimmunity, female-specific, estrogen
      dependent increase in splenic lymphocyte homing was directly implicated in
      increased disease severity. The present study evaluated the effect of estradiol
      on microvascular endothelial cells from the spleen compared to endothelial cells
      from the dermis, which has no disease manifestation in this model. Estradiol
      increased spleen endothelial cell estrogen receptor (ER) alpha 2.9-fold and
      decreased estrogen receptor beta 2.1-fold while decreasing both receptors on
      dermal cells. Estradiol enhanced adhesion of D10 cells to spleen but not dermal
      endothelial cells 1.53-fold (P < 0.001), an increase that was inhibited by
      antibodies to VCAM-1 and ICAM-1, and by the estrogen receptor antagonists
      tamoxifen and ICI 182,780. Estradiol induced greater VCAM-1 expression on spleen
      than dermal endothelial cells (P < 0.05). Estradiol increased spleen endothelial
      cell estrogen receptor alpha 2.9-fold and decreased estrogen receptor beta 2.1
      fold while decreasing both receptors on the dermal cells. Estrogen specifically
      and preferentially promoted spleen chemokine protein expression for MCP-1 and MCP
      3, while having no effect on dermal protein expression for these chemokines.
      Estradiol-mediated effects on splenic chemokines were abrogated by tamoxifen and
      ICI 182,780. The gender-specific increase in lymphocyte homing to spleen may be
      attributable, at least in part, to tissue-specific estrogen-mediated effects on
      microvascular endothelial cells.

PMID- 15501249
TI  - VEGF increases paracellular transport without altering the solvent-drag
      reflection coefficient.
AB  - Vascular endothelial growth factor (VEGF) increases microvascular permeability
      and has been implicated in the development of numerous pathologies including
      diabetic retinopathy (DR), hypoxia/ischemia, and tumor biology. The transport
      pathways by which water and solutes cross the endothelium in response to VEGF,
      however, are not completely understood. We measured, in real time, bovine retinal
      endothelial cell (BREC) hydraulic conductivity (Lp), 70 kDa dextran permeability
      (Pe), and the solvent-drag reflection coefficient (sigma) before and after
      addition of 50 ng/ml VEGF. The diffusional permeability coefficient for dextran
      (Pd) was measured before pressure gradient application. The sudden application of
      a 10-cm H2O hydrostatic pressure gradient induced water and solute fluxes that
      decayed to steady-state values after approximately 2 h. Subsequently, the
      addition of VEGF significantly increased Lp and Pe by 4.3-fold +/- 0.7-fold and
      3.0-fold +/- 0.3-fold, respectively, after 110 min; however, the reflection
      coefficient remained approximately constant throughout the experiment
      (approximately 0.8). These observations suggest that water and dextran utilize
      common paracellular channels across BREC monolayers. Furthermore, the addition of
      VEGF increases the number or availability of channels but does not alter the
      selectivity of the monolayer to 70 kDa dextran.

PMID- 15501250
TI  - Contractile responses of isolated rat mesenteric arteries to acute episodes of
      severe hypoxia and subsequent reoxygenation.
AB  - This study further investigates the mechanisms responsible for the effects of
      acute and severe hypoxia, and subsequent reoxygenation, on the contractility of
      isolated rat mesenteric arteries. In noradrenaline (NA)-contracted arteries,
      hypoxia caused a relaxation to near baseline levels. Reoxygenation resulted in an
      immediate transient contraction before tension returned more slowly to prehypoxia
      levels. Similar responses to hypoxia were observed in tissues precontracted by
      addition of KCl (60 mM) or U46619 (10 microM); however, the transient contraction
      upon reoxygenation was absent (KCl) or reduced (U46619). Responses to hypoxia
      were independent of changes in intracellular calcium ([Ca2+]i), while those to
      reoxygenation were accompanied by corresponding changes in [Ca2+]i and were
      completely abolished by ryanodine. In NA-contracted tissues, all responses were
      unaffected by endothelial removal or by inhibitors of nitric oxide synthase and
      cyclooxygenase. The K+ channel blockers triethylamine (TEA), glibenclamide, and 4
      aminopyridine (4-AP) had no effect on the responses to hypoxia. The transient
      contractile response to reoxygenation was, however, significantly reduced in the
      presence of 4-AP. The response to reoxygenation, but not that to hypoxia, was
      inhibited by the antioxidant dithiothreitol (DTT) and the NAD(P)H-oxidase
      inhibitor diphenyliodonium (DPI). These data suggest that hypoxic vasodilation
      occurs independently of reductions in [Ca2+]i. Alternatively, transient
      contractions on reoxygenation are dependent upon the generation of reactive
      oxygen species and the release of stored Ca2+.

PMID- 15501252
TI  - Biologic evaluation of curcumin and structural derivatives in cancer
      chemoprevention model systems.
AB  - Curcumin is a natural product widely used as a spice in food. It has been shown
      to inhibit cyclooxygenase (COX)-1 and -2 and to suppress lipopolysaccharide
      induced COX-2 and iNOS gene expression. In the present study, curcumin and 22 of
      its derivatives were evaluated for their chemopreventive potential. Based on COX
      2 inhibition, curcumin (IC50=15.9 microM), 1,7-bis(3-fluoro-4-hydroxyphenyl)-1,6
      heptadiene-3,5-dione (19) (IC50=23.7 microM) and 2,6-bis(3-fluoro-4
      hydroxybenzylidene)cyclohexanone (23) (IC50=5.5 microM) were found to be most
      potent. Tricyclic derivatives 2,6-bis(4-hydroxy-3
      methoxybenzylidene)cyclohexanone (10), 2,6-bis(4-hydroxy-3,5
      dimethoxybenzylidene)cyclohexanone (13) and 2,5-bis(4-hydroxy-3,5
      dimethoxybenzylidene)cyclopentanone (21) inhibited LPS-induced COX-2 and iNOS
      gene expression in murine macrophages with potency equal to curcumin. RT-PCR
      experiments demonstrated suppression of COX-2 and iNOS gene expression occurred
      at the transcriptional level. The most active compounds in the macrophage assays,
      13 and 23, were also the most cytotoxic, however. Topical application of
      curcumin, 10, 13, 21, and 6, a methoxy derivative of curcumin, showed strong
      inhibition of 12-O-tetradecanoyl-13-acetate (TPA)-induced ornithine decarboxylase
      (ODC) activity in mouse skin. These data suggest that structural elements
      responsible for COX-1 and COX-2 inhibition do not correlate well with those
      responsible for inhibiting COX-2 and iNOS gene expression, but elements capable
      of inhibiting COX-2 and iNOS gene expression also contribute to inhibition of TPA
      induced ODC activity. The most potent compounds in these assays, 10, 13 and 21,
      as well as curcumin, were further evaluated for inhibition of 7,12
      dimethylbenz(a)anthracene (DMBA)-induced preneoplastic lesion formation in a
      mouse mammary organ culture model, and dose-dependent responses were observed.
      Most potent effects were at concentrations between 1 and 5 microM for 10, 13 and
      21, and at 10 microM for curcumin. These data demonstrate the substitution
      pattern on the aromatic moiety is especially crucial for activity.

PMID- 15501253
TI  - Constituents of the stems of Macrococculus pomiferus and their inhibitory
      activities against cyclooxygenases-1 and -2.
AB  - As part of our program directed towards the discovery of new cancer
      chemopreventive agents from plants, the EtOAc-soluble extract of the stems of M.
      pomiferus was found to inhibit the enzyme cyclooxygenase-2 (COX-2). Bioassay
      directed fractionation of this extract led to the isolation of two
      dibenzylbutyrolactone lignans, (8R,8'R)-3'-O-demethyl-5-hydroxymatairesinol (1)
      and (8R,8'R)-3'-O-demethyl-5-methoxymatairesinol (2), as well as seven known
      compounds, (-)-5'-methoxyyatein (3), blumenol A, (-)-deoxypodophyllotoxin
      (anthricin), (-)-deoxypodorhizone, 2,6-dimethoxyhydroquinone, 4
      hydroxybenzaldehyde, and beta-sitosterol glucoside. The structures of compounds 1
      and 2 were determined using spectroscopic data (1D and 2D NMR, and HREIMS), and
      the 8R and 8'R absolute stereochemistry was established for both 1 and 2 on the
      basis of their CD spectra. All isolates obtained in the present study were
      evaluated for their inhibitory effects with both COX-1 and -2. Of these, only 5'
      methoxyyatein (3) showed weak activity against COX-2, while all other compounds
      isolated were inactive. The COX-2 inhibitory activity of the EtOAc extract was
      also traced to the presence of several common fatty acids by LC-MS.

PMID- 15501254
TI  - 4-Alkyl- and 4-phenylcoumarins from Mesua ferrea as promising multidrug resistant
      antibacterials.
AB  - Supercritical CO2 selectively extracted a series of 4-alkyl and 4-phenyl 5,7
      dihydroxycoumarins from Mesua ferrea blossoms. Chemical modifications of the
      isolated compounds allowed us to confirm the structures elucidated by
      spectroscopic means and to prepare new derivatives amenable to SAR studies and
      potential pharmaceutical development. Biological investigations towards the
      screening on a number of bacteria strains and Plasmodium falciparum, identified
      compounds 1-9 as weak antiprotozoal agents and potent antibacterials on resistant
      Gram-positive strains.

PMID- 15501255
TI  - Chemotaxonomic relevance of cardenolides in Urginea fugax.
AB  - In a chemotaxonomic approach the investigation of a methanolic extract of bulbs
      of Urginea fugax (MORIS) STEINH. resulted in the detection of several
      cardenolides. The structure of a novel compound, named fugaxin (1), was
      established as 12alpha,14beta-dihydroxy-2alpha,3beta-(tetrahydro-3',5'-dihydroxy
      4'-methoxy-6'-methyl-2H-pyran-2',4'-diylbisoxy)-card-4,20-dienolide by extensive
      NMR spectroscopic studies including 2D-NMR techniques (COSY, HSQC, HMQC) and
      selective 1D experiments (NOE, TOCSY) as well as HR-ESI-MS. The chemotaxonomic
      relevance of the occurrence of cardenolides in the genus Urginea is discussed.

PMID- 15501256
TI  - HPLC-based bioactivity profiling of plant extracts: a kinetic assay for the
      identification of monoamine oxidase-A inhibitors using human recombinant
      monoamine oxidase-A.
AB  - An assay for the HPLC-based search for monoamine oxidase-A (MAO-A) inhibitors in
      plant extracts was established. It combines human recombinant MAO-A, expressed as
      GST-fusion protein in yeast, with a kinetic measurement of the conversion of
      kynuramine to 4-hydroxyquinoline. Substrate selectivity and kinetic parameters of
      the GST-fusion protein were comparable to the wild-type enzyme. The applicability
      of the assay to HPLC-based activity profiling was tested with plant extracts
      spiked with small amounts of known MAO inhibitors.

PMID- 15501257
TI  - Choline esterase inhibitory properties of alkaloids from two Nigerian Crinum
      species.
AB  - The bulbs of Crinum jagus and Crinum glaucum are used in traditional medicine in
      southern Nigeria for memory loss and other mental symptoms associated with
      ageing. Alkaloidal extracts of bulbs from each species showed inhibition of
      acetylcholinesterase, an activity exploited therapeutically to raise the
      depressed levels of acetylcholine in the brain associated with Alzheimer's
      disease. Using the in situ bioautographic test method for enzyme inhibition, a
      number of alkaloids were isolated and their activity quantified using the Ellman
      spectrophotometric test. The most active alkaloids isolated were hamayne (IC50
      250 microM) and lycorine (IC50 450 microM) whilst other alkaloids were
      comparatively inactive with haemanthamane giving 3% inhibition and crinamine
      giving 4.4% inhibition at 50 mg ml(-1) (174 microM). These contrast with the
      positive control physostigmine which gave IC50 of 0.25 microM. Cholinesterase
      activity appears to be associated with the presence of two free hydroxy groups in
      this structural type of Amaryllidaceae alkaloid.

PMID- 15501258
TI  - Isolation of ginkgolides A, B, C, J and bilobalide from G. biloba extracts.
AB  - Ginkgolides A, B, C and J, together with bilobalide, are unique terpenoid
      components of the Ginkgo biloba tree. Due to similar chemical properties, their
      separation is quite tedious. We have developed an efficient and rapid protocol
      for separation of individual ginkgolides and bilobalide from G. biloba extracts.
      The procedure takes advantage of enhanced susceptibility of ginkgolides B and C
      to benzylation and the ease of separation of these products from ginkgolides A
      and J which do not react. The protocol is applicable to the previously reported
      enriched extracts prepared from G. biloba leaves. A single chromatographic step
      prior to benzylation provides bilobalide and mixture of ginkgolides A, B, C, and
      J. After benzylation, the individual ginkgolides are separated by chromatography.

PMID- 15501259
TI  - Ancistroheynine B and two further 7,3'-coupled naphthylisoquinoline alkaloids
      from Ancistrocladus heyneanus Wall.
AB  - A new axially chiral naphthylisoquinoline alkaloid, ancistroheynine B (7), has
      been isolated from the leaves of the Indian liana Ancistrocladus heyneanus Wall.,
      along with two known related alkaloids, ancistrocladidine (3) and
      ancistrotanzanine C (6), which are 7,3'-coupled, too. The structural elucidation
      was achieved by chemical, spectroscopic, and chiroptical methods. Biological
      activities of ancistroheynine B against the pathogens of malaria, leishmaniasis,
      Chagas' disease, and African sleeping sickness were evaluated.

PMID- 15501260
TI  - Kahiricosides II-V, cycloartane glycosides from an Egyptian collection of
      Astragalus kahiricus.
AB  - Four cycloartane-type saponins, kahiricosides II-V (1-4), were isolated from the
      aerial parts of Astragalus kahiricus of Egyptian origin. Their structures were
      established as 9beta,19-cyclolanost-24E-ene-3beta,6alpha,16beta,27-tetraol-3-O
      beta-D-glucopyranoside, 9beta,19-cyclolanost-24E-ene-3beta,6alpha,16beta,27
      tetraol-3-O-(2'-O-acetyl)-beta-D-glucopyranoside, 9beta,19-cyclolanost-24E-ene
      3beta,6alpha,16beta,27-tetraol-3-O-(6'-O-acetyl)-beta-D-glucopyranoside, and
      9beta,19-cyclolanost-24E-ene-3beta,6alpha,16beta,27-tetraol-3-O-beta-D
      glucopyranosyl-27-O-beta-D-glucopyranoside based on chemical and spectral
      evidences. All compounds exhibited very weak cytotoxicity against the A2780
      ovarian cancer cell line.

PMID- 15501261
TI  - Prenylated xanthones and tocotrienols from Garcinia virgata.
AB  - Two xanthones, namely virgataxanthone A and B, have been isolated from the stem
      bark of Garcinia virgata, together with two formylated tocotrienols and the known
      delta-tocotrienol, griffipavixanthone and 2,6-dihydroxy-4-methoxybenzophenone
      (cotoin). Their structures were mainly established using one and two-dimensional
      NMR and mass spectroscopies. When sufficient material was available, the
      antioxidant activities of the crude extracts as well as the isolated compounds
      were evaluated.

PMID- 15501262
TI  - Furostanol saponins and quercetin glycosides from the leaves of Helleborus
      viridis L.
AB  - Phytochemical analysis of the polar extracts of the leaves of Helleborus viridis
      (Ranunculaceae) resulted in the isolation of two new furostanol saponins (25R)-26
      [(alpha-L-rhamnopyranosyl)oxy]-22alpha-methoxyfurost-5-en-3beta-yl O-beta-D
      glucopyranosyl-(1-->3)-O-[6-acetyl-beta-D-glucopyranosyl-(1-->3)]-O-beta-D
      glucopyranoside (1) and (25R)-26-[(alpha-L-rhamnopyranosyl)oxy]-22alpha
      methoxyfurost-5-en-3beta-yl O-beta-D-glucopyranosyl-(1-->3)-O-beta-D
      glucopyranosyl-(1-->3)-O-beta-D-glucopyranoside (2) and three new quercetin
      glycosides, quercetin 3-O-(2-E-caffeoyl)-alpha-L-arabinopyranosyl-(1-->2)-beta-D
      galactopyranoside-7-O-beta-d-glucopyranoside (3), quercetin 3-O-(2-E-caffeoyl)
      alpha-L-arabinopyranosyl-(1-->2)-beta-D-galactopyranoside (4), and quercetin 3-O
      alpha-L-arabinopyranosyl-(1-->2)-beta-D-galactopyranoside (5). The structures of
      the new compounds were determined by spectroscopic analysis, including 2D NMR
      data and mass spectrometry.

PMID- 15501263
TI  - Cedkathryns A and B, pentanortriterpenoids from Cedrelopsis gracilis
      (Ptaeroxylaceae).
AB  - The stem bark of Cedrelopsis gracilis (Ptaeroxylaceae) has yielded three known
      prenylated coumarins, O-methylalloptaeroxylin, ptaerochromenol and umtatin and
      the novel pentanortriterpenoids, cedkathryn A and cedkathryn B.

PMID- 15501264
TI  - Steroidal saponins from the aerial parts of Tribulus pentandrus Forssk.
AB  - Seven new steroidal glycosides named pentandrosides A(1)-G(7) were isolated from
      the EtOH extract of the aerial parts of Tribulus pentandrus. Pentandrosides A(1)
      E(5) possess cholestane aglycones, pentandroside F(6) a furostan-type aglycone
      and pentandroside G(7) an unusual acyloxypregnane aglycone probably derived from
      the degradation of a furostan skeleton. Structure elucidation of 1-7 was
      accomplished through the extensive use of 1D- and 2D NMR experiments including 1H
      1H (DQF-COSY, 1D-TOCSY) and 1H-13C (HSQC, HMBC) spectroscopy along with ESIMS and
      HRESIMS.

PMID- 15501265
TI  - Secondary metabolites from the leaves of Feijoa sellowiana Berg.
AB  - The investigation of the lipid extract of leaves of Feijoa sellowiana cultivated
      along the east coast of Sicily has yielded in addition to the widespread
      secondary metabolites: alpha-tocopherol, flavone, stigmasterol and beta-carotene,
      an inseparable mixture of tyrosol esters of lignoceric (1a), cerotic (1b) and
      montanic (1c) acids, and a novel galactolipid identified as (2S)-1,2,6'-tri-O
      [(9Z,12Z,15Z)-octadeca-9,12,15-trienoyl]-3-O-beta-D-galactopyranosyl glycerol
      (2).

PMID- 15501267
TI  - Surgical education in the new millennium: the university perspective.

PMID- 15501268
TI  - Surgical education in the new millennium: a community hospital perspective.

PMID- 15501269
TI  - Surgical education in the new millennium: the military perspective.

PMID- 15501270
TI  - Surgical education in the new millennium: the European perspective.

PMID- 15501271
TI  - Supply and demand--surgical and health workforce.

PMID- 15501272
TI  - Professionalism in the match process: the rules and ethics of recruitment.

PMID- 15501273
TI  - Attrition and replacement of general surgery residents.

PMID- 15501274
TI  - Gender and diversity considerations in surgical training.

PMID- 15501275
TI  - The 80-hour workweek.

PMID- 15501276
TI  - Challenges of the 80-hour resident work rules: collaboration between surgeons and
      nonphysician practitioners.

PMID- 15501277
TI  - The impaired surgical resident.

PMID- 15501278
TI  - Defining general surgery and the core curriculum.

PMID- 15501279
TI  - Accreditation Council for Graduate Medical Education core competencies
      initiative: the road to implementation in the surgical specialties.

PMID- 15501280
TI  - Integrating technical competency into the surgical curriculum: doing more with
      less.

PMID- 15501281
TI  - Educating surgery residents in patient safety.

PMID- 15501282
TI  - Alternative training models for surgical residency.

PMID- 15501283
TI  - The beta-defensin-fold family of polypeptides.
AB  - Polypeptides adopting a fold very similar to that of beta-defensins are found in
      diverse organisms, including sea anemones, snakes, platypus and humans. These
      molecules of approximately 35-50 amino acid residues possess disparate
      activities, such as anti-microbial, myonecrotic, analgesic, and ion-channel
      inhibiting. The family of beta-defensin-fold structures generally consists of a
      short helix or turn followed by a small twisted anti-parallel beta-sheet. The six
      cysteine residues which are paired in a 1-5, 2-4, 3-6 fashion are crucial for
      determining and maintaining the compact core configuration of the structures. The
      primary structural similarity between members of the family suggests that the
      global fold is robust and that the nature of the side-chains determine the
      functional specificity. The distinct compact fold shared by these polypeptides
      may be useful in the design of molecules with desired pharmacological activity.

PMID- 15501284
TI  - Muscle and skin necrotizing and edema-forming activities of Duvernoy's gland
      secretion of the xenodontine colubrid snake Philodryas patagoniensis from the
      north-east of Argentina.
AB  - Philodryas patagoniensis is a colubrid snake spread by all South America, but
      very little is known about the composition and biological activities of its
      Duvernoy's gland secretion. In order to characterize it, we studied edematogenic,
      dermonecrotic and myonecrotic activities. For edematogenic activity, solutions
      containing different amounts of secretion were injected s.c. in the right foot
      pad of mice, both feet were subsequently cut off and weighed individually. For
      myonecrotic activity, mice were injected i.m. with solutions containing 40 microg
      of secretion, and at various time intervals mice were bled to determine serum
      creatine kinase activity and gastrocnemius muscles were removed for microscopic
      examination (Hematoxylin-Eosin stain). For dermonecrotic activity, solutions
      containing different amounts of secretion were injected into the shaved dorsal
      skin of mice; the necrotic lesion was measured on the inner surface of the skin
      and trimmed for microscopic examination (Hematoxylin-Eosin stain). Phospholipase
      A(2) activity was evaluated using a kinetic method. Results showed that P.
      patagoniensis Duvernoy's gland secretion exhibits a high edematogenic activity
      and moderate myonecrotic and dermonecrotic activities, while lacking
      phospholipase A(2) effect. Regarding edema, a 30% increase in the weight was
      produced by injecting 0.26 microg of Duvernoy's gland secretion. Microscopically,
      myonecrosis reached its highest intensity 12 h after injection, which was also
      demonstrated by serum creatine kinase levels. Dermonecrosis was proportional to
      the amount of secretion injected, with a minimum necrotizing dose of 15.7 microg.
      Myonecrotic, edematogenic and dermonecrotic activities were inhibited when the
      secretion was pre-incubated with 1 mM Na(2)EDTA. This suggests that the enzymes
      responsible for those activities are mostly metalloproeinases. All the studies
      carried out up to now demonstrate the potential toxicity of P. patagoniensis
      Duvernoy's gland secretion (which inhabits the north-east region of Argentina)
      and that the local lesions caused by this colubrid snake are very similar to
      those found in bothropic accidents. This latter suggests a more careful
      evaluation of the victims when considering the medical treatment to be adopted.

PMID- 15501285
TI  - Potential effects of tetrodotoxin exposure to human glial cells postulated using
      microarray approach.
AB  - Sodium channels play an important role in many neurological disorders and also in
      prostate cancer. Tetrodotoxin (TTX), a blocker of voltage-gated sodium channels
      has been chiefly used as a molecular probe for the study and characterization of
      these channels. The regulation of gene expression in response for the exposure of
      TTX to glial cells which are reported to be involved in neurodegenerative process
      is poorly understood. Therefore, the present study aims to develop a repository
      of genes and map it on a few pivotal neurodegenerative pathways to speculate the
      effect of TTX. Using Affymetrix GeneChip (HG-U133A), we have selected a subset of
      692 differentially expressed genes, several of which are-cullin 4A (CUL4A),
      ubiquitin carrier protein (E2-EPF), proteasome (prosome, macropain) subunit, beta
      type, 8 (large multifunctional protease 7) (PSMB8), protein tyrosine phosphatase
      type IVA (PTP4A1), intercellular adhesion molecule 1 (ICAM1), prostaglandin
      endoperoxide synthase 2 (PTGS2), and caspase 1 (CASP1). These genes, which
      facilitate some of the neurodegenerative pathways, such as ubiquitin, proteasome,
      inflammation and kinases, were identified to be up- or down-regulated for the TTX
      treatment. Thus, the selected genes were further examined on ubiquitin-proteasome
      mediated inflammatory responses pathway as ample evidence for the role of glial
      cell-mediated inflammation in the neurodegenerative process are available. In
      summary, our result provides a basic understanding of the differentially
      expressed genes along with one of the possible pathway which may have been
      modulated by the exposure of TTX.

PMID- 15501286
TI  - Immunosuppresive role of principal toxin (crotoxin) of Crotalus durissus
      terrificus venom.
AB  - The composition of the crotalic venom and the immunochemistry and/or
      pathophysiological characterization and main components were well studied.
      However, few studies have been carried out to investigate the effect of toxins of
      this venom on the development of the immune response. The objective of this work
      was to find out if venom or crotoxin of Crotalus durissus terrificus was able to
      modulate the immune response through its ability to change the mediators involved
      in the immune response by an unrelated antigen. We observed in the murine model,
      that venom as well as crotoxin have inhibitory effect on splenic cells
      proliferation induced by Con-A. Moreover, CB did not inhibit the proliferative
      response, suggesting that the integrity of crotoxin complex is necessary for the
      development of this phenomenon. Moreover, we showed that the effect on cellular
      proliferation was unrelated to cytotoxicity activity. We also observed that venom
      or crotoxin inhibited cytokine release induced in HSA immunised mice, mainly IL
      2, IL-4 and IL-10, however, crotoxin did not inhibit the release of IFN-gamma.
      The involvement of T or B cells in the suppressive effect of venom was evaluated
      through the transference of purified splenic cells from venom-mice to normal mice
      that also produced low IgG1 anti-HSA levels, indicating the participation of
      these cells in this process. Mechanism of action of the crotalic venom on
      development of immune response to an unrelated antigen is much more complex,
      therefore it must not only involve the interaction of distinct cellular
      populations, but activation or inhibition of signalling proteins, need to be
      further investigated.

PMID- 15501287
TI  - Epitope mapping of the antigenic protein TsNTxP from Tityus serrulatus scorpion
      venom using mouse, rabbit and sheep antibodies.
AB  - In the present investigation we used native and recombinant TsNTxP to elicit
      antibodies in three different animal models (mouse, rabbit and sheep).
      Differences among anti-TsNTxP antibodies were analyzed using sets of overlapping
      pentadecapeptides of the TsNTxP amino acid sequence and also modified peptides to
      reveal key residues in antibody-peptide binding. Despite the identification of
      similar peptides by the antibodies in the C and N-terminal, peculiarities of each
      system were observed including the level of reactivity and also the number and
      type of key residues in the continuous epitopes of TsNTxP. In addition, in vitro
      neutralization assays indicated that sheep are an alternative and efficient model
      for the production of anti-Tityus serrulatus venom.

PMID- 15501288
TI  - Lonomia obliqua caterpillar venom increases permeability of the blood-brain
      barrier in rats.
AB  - Human envenoming by caterpillars of the saturniid moth Lonomia obliqua in
      southern Brazil produces a mild local response (erythema, some edema, and pain)
      and systemic effects that include incoagulable blood, renal failure and in severe
      accidents intracerebral hemorrhage. In this work, we used light and electron
      microscopy to investigate the morphological alterations in the brain and blood
      brain barrier of rats injected intravenously with venom from L. obliqua spicules
      (200 microg/kg). Five semi-purified fractions of venom (200 microg/kg each) were
      also assayed. Quantitative morphological and ultrastructural analyses were done
      6, 18, 24 and 72 h after the i.v. injection of venom and its fractions. Light
      microscopy showed that 6h after envenoming there was cerebellar edema, which
      decreased by 72 h. Intracerebral hemorrhage occurred in only one rat 24h after
      the injection of venom. Blood-brain barrier (BBB) breakdown, assessed by
      transmission electron microscopy based on the passage of an extracellular tracer
      (lanthanum nitrate) between brain capillary endothelial cells, was observed in
      the cerebellum and hippocampus 18 h after venom injection. At this time, the
      cerebellum was more sensitive to the venom than the hippocampus, as shown by the
      greater number of leaky vessels. The number of capillaries showing breakdown was
      lower after 72 h than after 18 h. None of the semi-purified fractions
      significantly increased the number of leaky vessels. These results indicate that
      L. obliqua caterpillar venom has a deleterious action on the rat BBB. The lack of
      effect of the venom fractions when administered alone suggested that a
      synergistic action of venom components may be responsible for the damage seen in
      the central nervous system, but this was not confirmed when three combinations of
      the fractions were tested.

PMID- 15501289
TI  - Ontogenetic changes in Phoneutria nigriventer (Araneae, Ctenidae) spider venom.
AB  - Venom-yield and composition of differently sized individuals of the medically
      most important Brazilian spider Phoneutria nigriventer (Keyserling, 1891) was
      analysed. During growth the venom-mass increases according to a fourth order
      function of the prosoma size, which mainly reflects an increase of the venom
      gland volume. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed
      increasing percentages of proteins < or = 17 kDa from 4.1% in the smallest
      analysed spiders (2-3 months-old) to 79.1% in adult female venom. Additionally,
      high-pressure liquid-chromatography showed an increase of a single ('main') peak
      from 4.6 to 64.9%, while the overall number of other major-peaks decreased. Venom
      from young instars completely lacked lethality in mice up to a dose of 3.28 mg/kg
      i.v. as compared to a LD(50) of 0.63 mg/kg for adult female or 1.57 mg/kg for
      adult male venom that we reported previously. In conclusion, ontogenetic changes
      in venom protein-composition of growing P. nigriventer are suggested to produce
      increasing lethality in vertebrates.

PMID- 15501290
TI  - Two novel species of tetrodotoxin-producing bacteria isolated from toxic marine
      puffer fishes.
AB  - Out of eight dominant discrete bacterial colonies isolated and purified from the
      toxic marine puffer fishes collected in Hong Kong waters, two novel species of
      non-sporing, non-acid-fast and chemoorganotrophic bacteria capable of producing
      tetrodotoxin (TTX, a potent non-protein neurotoxin), as well as one previously
      reported and confirmed TTX-producing bacterium. They were identified as
      Microbacterium arabinogalactanolyticum, Serratia marcescens and Vibrio
      alginolyticus, respectively, all of which are widely distributed in soils, sewage
      or marine environments. Each bacterial isolate (500 ml broth medium cultured in
      darkness without aeration for 10 days at 25 degrees C) could produce an amount of
      toxicity, after extraction and purification, ranging from 78.3 to 105.3 mouse
      units (MU) in 500 ml of broth medium by mouse bioassay. The principal toxic
      component in the bacterial cultures was determined to be TTX by thin layer
      chromatography and mass spectrometry.

PMID- 15501291
TI  - TMVA, a snake C-type lectin-like protein from Trimeresurus mucrosquamatus venom,
      activates platelet via GPIb.
AB  - TMVA is a C-type lectin-like protein with potent platelet activating activity
      from Trimeresurus mucrosquamatus venom. In the absence of von Willebrand factor
      (vWF), TMVA dose-dependently induced aggregation of washed platelets. Anti-GP Ib
      monoclonal antibodies (mAbs), HIP1, specifically inhibited TMVA-induced
      aggregation in a dose-dependent manner. The aggregation was also inhibited by mAb
      P2 (an anti-GP IIb mAb). Flow cytometric analysis revealed that FITC-TMVA bound
      to human formalin-fixed platelets in a saturable manner, and its binding was
      specifically blocked by HIP1 in a dose-dependent manner. Flow cytometric analysis
      showed that TMVA did not bind to platelet GPIX, GPIIb, GPIIIa, GPIa, GPIIa and
      GPIV. Moreover, the platelet aggregation induced by TMVA was partially inhibited
      when platelet was pretreated with mocarhagin, a snake venom protease that
      specifically cleaves human GPIb. These results suggest that TMVA is a strong
      platelet agonist via GPIb and it might have multiple functional binding-sites on
      GPIb molecule or on other unknown receptor.

PMID- 15501292
TI  - Purification and characterization of paralytic shellfish toxin transforming
      enzyme from Mactra chinensis.
AB  - A carbamoylase, which catalyzes hydrolysis of the carbamoyl (or N-sulfocarbamoyl)
      moiety of paralytic shellfish toxins, was purified from the digestive glands of
      the Japanese clam Mactra chinensis. Using five steps of column chromatography,
      290 microg of Carbamoylase I showing homogeneity on SDS-PAGE was obtained.
      Carbamoylase I was revealed to be a glycoprotein, having estimated molecular
      weight of 190 kDa. Observation of single band equivalent to 94 kDa on SDS-PAGE
      under reducing conditions suggested it to be a homodimer. The optimal temperature
      and pH were 20 degrees C and 7.0. Carbamoylase I did not require a divalent
      cation and its activity was inhibited by the serine proteinase inhibitors,
      benzenesulfonyl fluoride and 4-(2-aminoethyl)-benzenesulfonyl fluoride.
      Carbamoylase I hydrolyzed both carbamate and N-sulfocarbamate toxins. The
      presence or absence of a hydroxyl moiety at the N-1 position of the substrate
      toxins did not significantly alter the reaction rate, but the stereochemistry of
      sulfate esters at C-11 greatly affected it. The K(m) was 3.02 microM for
      saxitoxin as a substrate. Nineteen amino acids of the N-terminal sequence were
      identified by the Edman method. MALDI-TOF-MS/MS spectra of (18)O-labeled tryptic
      peptides indicated the possible internal amino acid sequences of five peptides.

PMID- 15501293
TI  - Pharmacological effects of the marine toxins, brevetoxin and saxitoxin, on murine
      frontal cortex neuronal networks.
AB  - Brevetoxins and saxitoxins (STXs), which are produced by marine dinoflagellates,
      are very potent neurotoxins targeting separate sites of the alpha subunit of
      voltage-dependent sodium channels (VDSCs). An attractive approach for marine
      toxin detection relies on pharmacological modulation of VDSCs expressed in cells
      or tissues. While these function-based cellular assays exhibit the required
      sensitivity, they are typically slow and have limited potential use for field
      applications. Cultured neuronal networks grown on substrate integrated
      microelectrode arrays (MEAs) have emerged as a robust and sensitive approach for
      environmental threat detection. The present work describes the rapid effects of
      brevetoxin-2 (PbTx-2) and STX on embryonic murine frontal cortex neuronal
      networks on MEAs. Network recording parameters such as mean spike rate, burst
      rate, burst duration, number of spikes per burst and spike amplitude were
      analyzed before and after exposure to the toxins. STX produced fast and
      reversible inhibition of all electrophysiological parameters with IC(50)s ranging
      between 1.2 and 2.2nM. Although PbTx-2 also caused inhibition of most of the
      network electrophysiological parameters, it produced an increase in burst
      duration at lower concentrations (EC(50)=15+/-2 nM, n=4) followed by inhibition
      at higher ones (IC(50)=63+/-4 nM, n=4). Exposure of frontal cortex networks to
      PbTx-2 and STX also caused differential effects on spike amplitude. This work
      demonstrates that cultured neuronal networks not only could be used for
      pharmacological characterization of marine toxins but they also provide a tool
      with unique properties for their detection.

PMID- 15501294
TI  - Brevetoxin metabolism and elimination in the Eastern oyster (Crassostrea
      virginica) after controlled exposures to Karenia brevis.
AB  - The metabolism and elimination of brevetoxins were examined in the Eastern oyster
      (Crassostrea virginica) following controlled exposures to Karenia brevis cultures
      in the laboratory. After a 2-day exposure period ( approximately 62 million
      cells/oyster), elimination of brevetoxins and their metabolites was monitored by
      using liquid chromatography/mass spectrometry (LC/MS). Composite toxin in oyster
      extracts was measured by in vitro assay (i.e. cytotoxicity, receptor binding, and
      ELISA). Of the parent algal toxins, PbTx-1 and PbTx-2 were not detectable by
      LC/MS in K. brevis-exposed oysters. PbTx-3 and PbTx-9, which are accumulated
      directly from K. brevis and through metabolic reduction of PbTx-2 in the oyster,
      were at levels initially (after exposure) of 0.74 and 0.49 microg equiv./g,
      respectively, and were eliminated largely within 2 weeks after dosing. PbTx-7 and
      PbTx-10, the reduced forms of PbTx-1, were non-detectable. Conjugative brevetoxin
      metabolites identified previously in field-exposed oysters were confirmed in the
      laboratory-exposed oysters. Cysteine conjugates of PbTx-1 and PbTx-2, and their
      sulfoxides, were in the highest abundance, as apparent in LC/MS ion traces, and
      were detectable for up to 6 months after dosing. Composite toxin measurements by
      in vitro assay also reflected persistence (up to 6 months) of brevetoxin residues
      in the oyster. Levels of cysteine conjugates, as determined by LC/MS, were well
      correlated with those of composite toxin, as measured by ELISA, throughout
      depuration. Composite toxin levels by cytotoxicity assay were well correlated
      with those by receptor binding assay. Cysteine-PbTx conjugates are useful LC/MS
      determinants of brevetoxin exposure and potential markers for composite toxin in
      the Eastern oyster.

PMID- 15501295
TI  - Analgesic and behavioral effects of amphetamine enantiomers, p-methoxyamphetamine
      and n-alkyl-p-methoxyamphetamine derivatives.
AB  - The analgesic effects of (+)- and (-)-amphetamine (AMPH), (+/-)-p
      methoxyamphetamine (MA), (+/-)-N-methyl-p-methoxyamphetamine (MMA) and (+/-)-N
      ethyl-p-methoxyamphetamine (EMA) were compared using two different algesimetric
      tests in rats. In the formalin test, (+)-AMPH elicited significant
      antinociception at doses of 0.2, 2 and 8 mg/kg (i.p.); (-)-AMPH was active at 2
      and 8 mg/kg, but not at 0.2 mg/kg; MA elicited very potent and long-lasting
      antinociception; MMA was less active than MA; EMA showed significant effects only
      at doses of 2 and 8 mg/kg. In the C-fiber evoked nociceptive reflex assay, i.v.
      (+)- and (-)-AMPH were ineffective, but the methoxy derivatives showed a similar
      pattern of action combining inhibitory and excitatory actions. To clarify
      apparent discrepancies between both algesimetric tests, some behavioral motor
      performance tests were carried out. These tests confirm the motor stimulatory
      properties of (+)-AMPH, not shared by the methoxylated amphetamine derivatives.
      The three methoxy derivatives elicited some stereotypies related to dopaminergic
      activation such as grooming behavior. (+)-AMPH was also the only drug to increase
      the acquisition of CARs while MA and EMA were without effect. Avoidance
      conditioning was seriously impaired in rats injected with MMA. This conditioned
      behavior can be related to the significant decrease of spontaneous motor activity
      observed with this drug. In conclusion, the introduction of a para-methoxy group
      strongly increases the analgesic effects of amphetamine without its stimulatory
      behavioral effects. The introduction of N-alkyl substituents decreases the
      analgesic potency of MA.

PMID- 15501296
TI  - Social crowding sensitizes high-responding rats to psychomotor-stimulant effects
      of morphine.
AB  - Large individual differences have been identified toward varied addictive effects
      as evidenced in self-administration, place conditioning, and psychomotor
      stimulation paradigms, which have been primarily attributed to the role of
      congenital factors. However, it remains unknown whether environmental factors,
      like extraneous social stress events, could distinctively modulate animals with
      differentiated biobehavioral traits, such as rats with higher motor activity
      (high responder, HR) developed in a novel environment and their counterparts, LR
      (low responder) rats. In the present study, the influence of social crowding
      procedure upon morphine psychomotor effect was investigated. Moreover, the roles
      social stress played, respectively, on HRs and LRs were explored based on
      previous observation that HRs not only responded more to drugs but also to
      stress. Our results revealed that social crowding procedure could sensitize
      morphine psychomotor effect as a whole, and this effect was only evident for HR
      but not LR rats. The individual differences toward morphine psychomotor effects
      was indiscernible in rats housed in normal social conditions and only turned out
      to be significant under stress conditions. Given the fact that the occurrence of
      human addictive behavior usually happens within social environment permeated with
      various stress factors, the genetic and environmental elements may
      collaboratively contribute to the ultimate susceptibility of drug-prone
      individuals.

PMID- 15501297
TI  - Effects of abused inhalants and GABA-positive modulators in dizocilpine
      discriminating inbred mice.
AB  - There is in vitro evidence that some of the effects of abused volatile solvents
      may be produced by actions at the NMDA receptor. In addition, some solvents
      produce phencyclidine-like discriminative stimulus effects. The major goal of the
      present study was to further compare abused solvents to NMDA antagonists by
      testing them in two strains of mice trained to discriminate 0.17 mg/kg of the
      very selective uncompetitive NMDA antagonist, dizocilpine, from saline and
      contrast those results with several GABA(A)-positive modulators, PCP and ethanol.
      The results indicated that the discriminative stimulus produced by 0.17 mg/kg
      dizocilpine was highly specific in both mouse strains. PCP produced 91%
      dizocilpine-lever responding in C57BL/6J mice, but only 56% dizocilpine-lever
      responding in DBA/2J mice. Pentobarbital, midazolam and ethanol produced at least
      some overlap in discriminative stimulus effects with dizocilpine in one or both
      mouse strains. In contrast, toluene, 1,1,1-trichloroethane (TCE), xylene and
      methoxyflurane produced saline-appropriate responding almost exclusively. These
      data indicate that, at least under the specific conditions tested, abused
      volatile solvents do not have substantial dizocilpine-like discriminative
      stimulus effects in either C57BL/6J or DBA/2J mice, providing little support that
      NMDA antagonism plays a central role in the production of this abuse-related
      effect.

PMID- 15501298
TI  - Socially mediated alcohol preferences in adolescent rats following interactions
      with an intoxicated peer.
AB  - This study focuses on "passive social influences" (alcohol-related information
      acquired by an organism that interacts with an intoxicated counterpart) that can
      potentially affect alcohol preference in adolescent rats. Five experiments were
      conducted to investigate whether repeated social interactions with an intoxicated
      peer can generate alcohol-related memories that lead an animal to exhibit
      heightened alcohol olfactory preference patterns. Juvenile experiences with
      alcohol were operationalized as follows: interactions with an alcohol-intoxicated
      peer (Experiment 1), with an alcohol-scented cotton surrogate (Experiment 2) or
      with an anesthetized alcohol-intoxicated partner (Experiments 3-5).
      Periadolescents were then evaluated in a two-way location olfactory test where
      they had the opportunity to investigate a hole scented with alcohol odor or
      vanilla (an odorant naturally preferred by the strain of rats here utilized).
      Only juveniles that interacted with an alcohol-intoxicated peer were found to
      exhibit a significant change in alcohol odor preferences when compared to
      appropriate controls that interacted with a non-intoxicated peer. Alcohol odor
      exposure alone or interactions with an anesthetized alcohol-intoxicated peer were
      not sufficient to establish changes in preference for alcohol sensory cues.
      Results indicate that social interactions with an intoxicated peer determine
      heightened preference for alcohol cues in periadolescents. The establishment of
      this preference seems to require behavioral manifestations of the intoxicated
      counterpart, instead of just being dependent on an olfactory pre-exposure to
      alcohol cues.

PMID- 15501299
TI  - Bone cancer pain model in mice: evaluation of pain behavior, bone destruction and
      morphine sensitivity.
AB  - The primary aim of the study was to correlate pain development during bone cancer
      growth with objectively obtained tumor-induced changes in bone morphology.
      Additionally morphine sensitivity of this bone pain was evaluated. Mice were
      injected into the femur with osteolytic NCTC2472 cells, and behaviorally followed
      during a 3-week period. During the observation period increasing pain behavior
      was observed in tumor-bearing animals. Tumor mice exhibited spontaneous and
      movement-evoked lifting, the latter evoked through non-noxious palpation of the
      tumor. Limb use during forced ambulation on a rotarod decreased to substantial
      non-use of the affected limb by day 23. On day 23, micro-computer tomography
      scans of the tumor-bearing bones were evaluated for bone destruction. Different
      bone parameters indicative of osteolysis or fragmentation were significantly
      correlated with pain behavior. In a separate group of mice the effects of
      different morphine doses on pain behavior were evaluated on days 17 and 21 of
      tumor growth. Spontaneous lifting and movement-evoked lifting were sensitive to
      morphine treatment, although stress-induced analgesia due to repeated restraint
      might minimize movement-evoked lifting in mice. Limb use during forced ambulation
      was only slightly ameliorated by high morphine doses.

PMID- 15501300
TI  - Decrease of immobility behavior in forced-swimming test and immune system
      enhancing effect of traditional medicine Gamisipjundaebo-tang.
AB  - Gamisipjundaebo-tang (GSDBT) has been used for the purpose of development of
      physical strength. In the present study, we investigated the immune enhancing
      effect induced by GSDBT. We investigated the anti-immobility effect of GSDBT via
      a forced-swimming test and blood biochemical parameters related to fatigue,
      glucose, blood urea nitrogen, lactic dehydrogenase, creatine kinase, and total
      protein. GSDBT (0.1 and 1 g/kg) was orally administered to mice for 14 days.
      After 7 and 14 days, as assessed through a forced-swimming test, immobility time
      was decreased in the GSDBT-administrated group (0.1 and 1 g/kg) in comparison
      with the control group. In addition, after 8 days, the contents of glucose and
      lactate dehydrogenase in the blood serum were increased, and contents of blood
      urea nitrogen were decreased in the GSDBT-administrated group. After 15 days, the
      contents of glucose were increased, and the contents of lactate dehydrogenase and
      blood urea nitrogen were decreased in the GSDBT-administrated group. However, it
      had no effect on the elevation of creatine kinase and total protein level. We
      also investigated the effect of GSDBT on the production of cytokines in human T
      cell line, MOLT-4 cells, and splenocytes. GSDBT significantly increased
      interferon (IFN)-gamma and interleukin (IL)-2 levels compared with the media
      control but did not affect IL-4. GSDBT increased the protein expression of IFN
      gamma in MOLT-4 cells. These results suggest that GSDBT may be useful in immune
      function improvement and may also have antifatigue properties.

PMID- 15501301
TI  - Direct relation between etonitazene dose and response rate: responding under a
      single FI per session.
AB  - Response-contingent injections of etonitazene (ETZ) have been shown to reinforce
      rats' lever pressing behavior. The objective of the present study was to
      determine the relation between response rate and ETZ dose when ETZ was
      administered subcutaneously once per session by the experimenter contingent upon
      completion of a 10-min fixed-interval (FI) schedule. When injections of the
      saline vehicle replaced drug injections, response rates dropped to low levels;
      rates subsequently increased above saline levels when drug injections were
      reintroduced, demonstrating that ETZ was serving as a reinforcer. A range of ETZ
      doses (0.01, 0.1, 1, 5.7, and 10 microg/kg) was administered subcutaneously to
      six rats, resulting in response rates that were directly related to drug dose.
      These findings are consistent with other studies that have found an increase in
      reinforcing effects with increases in drug dose. Thus, studies in which drug is
      administered once per session may be used to measure the reinforcing effects of
      drugs directly from rate measures, as the response rate in these studies is
      unaffected by satiation or direct drug effects.

PMID- 15501302
TI  - Prevention of diazepam withdrawal syndrome by nifedipine-behavioural and
      neurochemical studies.
AB  - Our studies aimed at investigating whether the dihydropyridine calcium
      antagonist, nifedipine, could prevent anxiogenic-like consequences of diazepam
      withdrawal in rats. Animals withdrawn from chronic diazepam (2 mg/kg/day i.p. for
      2 weeks) drank significantly less water than did control rats in the unfamiliar
      arm of a Y maze. This anxiogenic-like effect could be prevented by acute
      administration of nifedipine (at 10 mg/kg i.p., but not at lower doses), which,
      on its own, did not change water intake in naive rats. Given chronically in
      combination with diazepam for the second half of a 2-week treatment with this
      drug, nifedipine (at the daily dose of 5 mg/kg i.p.) also suppressed the
      reduction of water intake normally observed on diazepam withdrawal. Biochemical
      measurements showed that acutely, as well as chronically, administered nifedipine
      increased 5-HT turnover in the hippocampus of diazepam-treated rats, thereby
      suggesting that the prevention of diazepam withdrawal-induced anxiogenic
      behaviour by the calcium antagonist might be underlain by serotoninergic
      mechanisms.

PMID- 15501303
TI  - Bidirectional effects of benzodiazepine binding site ligands in the elevated plus
      maze: differential antagonism by flumazenil and beta-CCt.
AB  - Recent research using genetically modified mice has pointed to the specific
      contribution of individual receptor subtypes to the various effects of
      benzodiazepines. The aim of this study was to examine the relative significance
      of alpha(1)-containing GABA(A) receptors in the effects of modulators at the
      benzodiazepine site in the elevated plus-maze (EPM) under dim red light in rats.
      We tested the effects of the non-selective antagonist flumazenil (0-20.0 mg/kg),
      the preferential alpha(1)-subunit selective antagonist beta-carboline-3
      carboxylate-t-butyl ester (beta-CCt, 0-30.0 mg/kg), the non-selective agonist
      midazolam (0-2.0 mg/kg), the preferential alpha(1)-subunit selective agonist
      zolpidem (0-2.0 mg/kg) and the non-selective inverse agonist methyl 6,7-dimethoxy
      4-ethyl-beta-carboline-3-carboxylate (DMCM, 0-2.0 mg/kg). The influence of
      flumazenil (10.0 mg/kg) and beta-CCt (30.0 mg/kg) on the effects of both kinds of
      agonists were also examined. The standard spatio-temporal parameters reflecting
      anxiety (percentage of open arm entries and time) and locomotion (closed and
      total arm entries) were analyzed. beta-CCt did not affect behavior, while
      flumazenil at the highest dose (20.0 mg/kg) decreased indices of open arm
      activity and total arm entries. Midazolam at the dose of 1.0 mg/kg significantly
      increased the percentage of open arm time, whereas at 2.0 mg/kg both anxiety
      related parameters were increased. In contrast to the open arm entries, the open
      arm time was independent of the decreased closed arm entries, observed at 2.0
      mg/kg. Flumazenil abolished these effects, whereas beta-CCt partially potentiated
      the anxiolytic actions of midazolam. Zolpidem significantly increased both open
      arm indices at 1.0 mg/kg, but the effect was dependent on the decreased closed
      arm entries. The selectivity of the anxiolytic-like effects of zolpidem was
      further checked under brighter white illumination. In these settings, the
      influence on anxiety-related, but not activity-related parameters, was absent.
      All of the activity-related effects of midazolam and zolpidem were mainly
      counteracted by both antagonists. DMCM produced significant anxiogenic effects at
      1.0 mg/kg (open arm time) and 2.0 mg/kg (both parameters). beta-CCt (30.0 mg/kg)
      and flumazenil at higher dose (20.0 mg/kg) antagonized the effects of DMCM. The
      results indicate the anxiolytic effects of a non-selective benzodiazepine site
      agonist involve a predominant role of subunits other than alpha(1), whereas the
      behavioral indices of the anxiolytic-like properties of an alpha(1)-selective
      ligand, if observed, depend on the experimental settings and the changes in
      locomotor activity, and hence were behaviorally non-specific. The present results
      generally correspond well to the behavioral findings with the genetically
      modified mice. On the other hand, the relative significance of the alpha(1)
      subunit in the anxiogenic effects of DMCM could not be clearly deduced.

PMID- 15501304
TI  - Motivation of heroin-seeking elicited by drug-associated cues is related to total
      amount of heroin exposure during self-administration in rats.
AB  - Conditioned stimuli (CSs) previously associated with heroin are critically
      involved in activating long-lasting relapse and compulsive drug seeking. This
      study examined the magnitude of heroin seeking induced by drug-related cues in
      relation to the total amount of drug exposure during training. Five groups of
      male Sprague-Dawley rats (n=6/group) were trained by the nose-poking response to
      self-administer different doses of heroin (0, 0.01, 0.025, 0.05, and 0.1 mg/kg
      per infusion respectively, one 4-h session daily, limited to 25 infusions per
      session) under an identical progressive ratio schedule with gradual incremental
      response requirements. All the rats established stable heroin self-administration
      within 14 days of self-administration training, and the time needed to obtain all
      the 25 heroin infusions decreased across sessions. After 14 days of abstinence,
      heroin seeking elicited by contextual cues (self-administration chamber) or
      discrete contingent CSs previously associated with heroin infusions was measured
      in two consecutive 1-h test phases. During both test phases, the rats trained
      with heroin even at the lowest dose (0.01 mg/kg) showed higher active responses
      than saline controls, and the active responses were also higher in rats trained
      with doses of 0.025, 0.05, and 0.10 mg/kg in comparison with those trained with a
      dose of 0.01 mg/kg. There was no observable dose-dependence increase of responses
      at doses above 0.025 mg/kg. The results suggested that an increased motivation to
      seek heroin induced by drug-related cues is associated with the total amount of
      heroin intake.

PMID- 15501305
TI  - Anti-inflammatory and anti-hyperalgesic effects of sesquiterpene lactones from
      Magnolia and Bear's foot.
AB  - Sesquiterpene lactones possess a variety of biological activities, including anti
      inflammatory activity. Two plants native to the southeastern United States,
      Magnolia grandiflora (L.) and Smallanthus uvedalius (L.) [syn Polymnia uvedalius
      (L.)], are novel sources of the sesquiterpene lactones parthenolide and enhydrin,
      respectively. In this study, the anti-inflammatory and anti-hyperalgesic effects
      of these isolated lactones from these two plant sources were evaluated in the rat
      carrageenan inflammation model. Rats received ip injections of either vehicle
      (propylene glycol), indomethacin (5 mg/kg), 11,13-dihydroparthenolide (20 mg/kg),
      parthenolide (5 or 20 mg/kg) or enhydrin (5 or 20 mg/kg). A 100-microl injection
      of 2.0% carrageenan was made into the plantar surface of the right hindpaw. Paw
      withdrawal latencies and paw volumes in both inflamed and non-inflamed paws were
      recorded at four test intervals: pre-inflammation baseline (0 time point), and 1,
      2 and 4 h post-carrageenan injection. Vehicle-treated animals exhibited a
      significant time-dependent hyperalgesic and edema response that was greatest at
      the 4-h test interval. Indomethacin significantly blocked the hyperalgesic
      response and modestly attenuated the edema response. Parthenolide (20 mg/kg) and
      enhydrin (20 mg/kg) significantly blocked the hyperalgesic response and
      significantly attenuated the edema response; 11,13-dihydroparthenolide did not
      affect either inflammation or hyperalgesia. These findings suggest that
      parthenolide and enhydrin from these plant sources may be useful in the treatment
      of inflammatory pain.

PMID- 15501306
TI  - Lithium-chloride-induced conditioned taste aversions in the Lewis and Fischer 344
      rat strains.
AB  - Conditioned taste aversions (CTAs) are differentially induced by cocaine and
      morphine in the Lewis and Fisher 344 (LEW and F344, respectively) rat strains.
      Although the acquisition of LiCl-induced aversions has recently been reported to
      be comparable between the two strains, these aversions were induced by the oral
      consumption of LiCl, and the possibility exists that, given their different
      weights, that differential doses were functionally administered. To address the
      issue of LiCl-induced aversions in LEW and F344 rats (and to control for this
      possible confound), the present study assessed the ability of intraperitoneally
      (ip) administered LiCl to induce aversions in the two strains. Specifically, rats
      from both strains were given 20-min access to saccharin and injected immediately,
      thereafter, with 0.3, 0.6, 0.9 or 1.2 mEq/kg, 0.15 M LiCl (or its distilled water
      vehicle). Under these conditions, both strains acquired dose-dependent aversions
      that increased over repeated trials. Although there was no overall strain
      difference in LiCl-induced aversions, LEW rats displayed a stronger aversion at
      the 0.3 mEq/kg dose (on Trial 3) and acquired the aversion at this dose more
      rapidly than the F344 rats did (by Trial 2 vs. Trial 3). Although evident, this
      strain difference with LiCl does not parallel that reported with morphine (in
      which F344 rats are more sensitive than LEW rats) or with cocaine (in which the
      differences between LEW and F344 rats are larger and occur at more doses and on
      more trials). These cross-drug comparisons suggest that strain differences in
      aversion learning are drug dependent. Because drug acceptability has been
      reported to be a function of the balance between the reinforcing and aversive
      effects of various compounds, the examination of possible strain differences in
      aversion learning with a range of such compounds may provide insight into drug
      acceptability (and use) in these strains.

PMID- 15501307
TI  - Alpha2-adrenergic inhibition prevents the accompanied anticonvulsant effect of
      swim stress on behavioral convulsions induced by lithium and pilocarpine.
AB  - There has been much debate regarding the potential influence of stress on
      epilepsy. Many studies have reported that stress can affect seizure
      susceptibility through eliciting either proconvulsant or anticonvulsant effects
      within the nervous system. In this study, we investigated the potential
      anticonvulsant effect of a 10-min swim stress on convulsions induced by a single
      systemic injection of lithium chloride followed 4 h later with pilocarpine. Rats
      pretreated with lithium chloride and exposed to a 10-min swim stressor prior to
      pilocarpine injection displayed a significant delay to seizure onset compared to
      unstressed rats or rats exposed to swim stress 10 min after lithium chloride, 2 h
      after lithium chloride, or immediately after pilocarpine injection. We then
      determined whether administration of a glucocorticoid antagonist (mifepristone;
      10 or 50 mg/kg), an alpha(2)-adrenergic antagonist (yohimbine; 2 or 5 mg/kg), or
      a nonspecific opioid blocker (naloxone; 0.2 or 1 mg/kg) could prevent the
      anticonvulsant effect of swim stress. Only the high dose of yohimbine was capable
      of inhibiting the anticonvulsant effect of swim stress on lithium-pilocarpine
      seizures. Our findings highlight the importance of an endogenous noradrenergic
      dependent anticonvulsant system in mediating the effects of swim stress on
      seizures. Further studies exploring the benefits of treatments with noradrenergic
      acting drugs in epilepsy is well warranted.

PMID- 15501308
TI  - Heroin attenuates the negative consequences of cocaine in a runway model of self
      administration.
AB  - It has been presumed that the combination of cocaine (COC)+heroin (HER) is more
      reinforcing than either of the two drugs alone, thus leading to their
      coadministration ("speedballing"). An alternative hypothesis is that HER serves
      to attenuate the undesired negative effects of COC. To test this notion, male
      Sprague-Dawley rats (n=31) were trained to run a straight alley for a daily
      intravenous (IV) injection of COC (1.0 mg/kg/injection) for 14 trials. Studies in
      our laboratory have shown that such animals begin to exhibit approach-avoidance
      behaviors ("retreats") stemming from concurrent positive and negative
      associations with the goal box (which, in turn, are the result of COC's immediate
      rewarding and subsequent dysphoric actions). Thus, retreats can be used as a
      reliable index of COC's anxiogenic side effects. Following 14 COC-reinforced
      trials, animals were split into three groups matched on mean retreat frequency.
      One group (n=11) received IV COC (1.0 mg/kg/injection) for seven additional
      trials; the remaining two groups (n=10 each) received an IV injection of COC
      mixed in a single solution with either a low dose (0.025 mg/kg/injection) or a
      high dose (0.1 mg/kg/injection) of HER. It was hypothesized that adding HER would
      attenuate the negative consequences of COC administration and thereby produce a
      reliable decrease in the occurrence of retreats. The resulting data were
      consistent with this hypothesis, suggesting that "speedballing" in human addicts
      may be motivated by a desire to reduce the negative impact of COC use.

PMID- 15501309
TI  - Effects of amphetamine, dexfenfluramine, and diazepam on responding during
      extinction in nonhuman primates.
AB  - The effects of pharmacological manipulations on responding under extinction
      conditions were determined in baboons using a schedule of reinforcement that
      modeled food acquisition and food consumption. Responding during the initial
      acquisition component was reinforced by stimuli paired with food, while
      responding during the latter consumption component was reinforced with food.
      Certain sessions began with a 7-h extinction phase, where responding in both
      components produced only the paired stimuli. Dexfenfluramine (DFEN) decreased
      responding during extinction. Diazepam (DZP) increased responding during
      extinction. Low doses of amphetamine (AMPH) increased responding during
      extinction. Thus, DZP and AMPH increased and DFEN decreased the conditioned
      reinforcing effects of stimuli paired with food.

PMID- 15501310
TI  - Preexposure to MDMA ("Ecstasy") delays acquisition but facilitates MDMA-induced
      reinstatement of amphetamine self-administration behavior in rats.
AB  - The current experiment investigated the effect of 3,4
      methylenedioxymethamphetamine (MDMA; 'Ecstasy') preexposure on the acquisition of
      intravenous amphetamine self-administration and the reinstatement of amphetamine
      seeking behavior by either MDMA or amphetamine. Rats were preexposed to a 5-HT
      depleting regime of MDMA (5 mg/kg every hour for 4 h on two consecutive days) or
      equivalent vehicle injections. Intravenous self-administration of low dose d
      amphetamine (0.03 mg/kg/infusion) on a FR1 schedule was subsequently assessed.
      The rats were then given 2 weeks of extinction and tested for drug-seeking
      behavior with priming doses of amphetamine or MDMA. Brains were analysed for
      monoamine content using high-performance liquid chromatography (HPLC). MDMA
      preexposed rats were initially slower to acquire amphetamine self-administration.
      However, by day 6 of acquisition, there was no difference from controls.
      Following extinction, amphetamine (1 mg/kg, i.p.) reinstated drug seeking and
      produced locomotor hyperactivity in both MDMA- and vehicle-pretreated animals.
      However, MDMA (5 mg/kg, i.p.) was only effective in producing amphetamine seeking
      and hyperactivity in MDMA-pretreated rats. MDMA pretreatment caused significant
      decreases in 5-hydroxy-indolacetic acid (5-HIAA) and 5-HT in several brain
      regions. These results suggest that 5-HT depletion induced by MDMA may initially
      slow the acquisition of amphetamine self-administration but that MDMA preexposure
      may also sensitize animals to the locomotor stimulating and priming effects of
      MDMA on drug-seeking behavior.

PMID- 15501311
TI  - Baclofen interactions with nicotine in rats: effects on memory.
AB  - Nicotine has been shown in numerous previous studies to significantly improve
      memory on the radial-arm maze, yet the critical mechanisms underlying this effect
      are not fully characterized. Nicotine stimulates the release of a number of
      neurotransmitters important for memory function including (gamma-aminobutyric
      acid) GABA. The importance of nicotinic-GABA interactions regarding memory is
      currently unknown. The purpose of the current study was to determine the
      interactive effects of nicotine and the GABA agonist baclofen on working memory
      function as measured by choice accuracy in the radial-arm maze. Female Sprague
      Dawley rats trained to asymptotic performance levels on a win-shift eight-arm
      radial maze task were used for assessment of nicotine-baclofen interactions. Low
      doses of baclofen improved memory performance while higher doses impaired it.
      Nicotine, as seen before, improved memory performance. Nicotine also
      significantly reversed the higher dose baclofen-induced deficit. These data show
      the importance of both nicotinic and GABA systems in working memory function and
      the interactions between these two transmitter receptor systems. This not only
      provides information concerning the neural bases of cognitive performance, it
      also lends insight into new combination treatments for memory impairment.

PMID- 15501312
TI  - Differential effects of naproxen and rofecoxib on the development of
      hypersensitivity following nerve injury in rats.
AB  - The present study was undertaken to determine the effects of cyclooxygenase (COX)
      inhibitors on the development of neuropathic pain in rats following chronic
      constriction injury (CCI). A single intraperitoneal administration of naproxen, a
      nonselective COX inhibitor (10 or 30 mg/kg), or rofecoxib, a selective COX-2
      inhibitor (3 or 10 mg/kg) 2 h before nerve injury did not attenuate the
      development of neuropathic state for 28 days. However, the administration of
      naproxen [10 or 30 mg/kg, intraperitonelly (i.p.)], but not rofecoxib (3 or 10
      mg/kg, i.p.), on day 7 attenuated hypersensitivity but did not alter its
      development for 28 days. Furthermore, naproxen significantly reduced hyperalgesia
      and allodynia for 4 h, but the efficacy was not observed 24 h after the
      treatment, whereas rofecoxib failed to modify the hypersensitivity following
      perineural (p.n.) or intrathecal (i.t.) administration on day 7. Chronic
      administration of naproxen (3, 10 or 30 mg/kg), but not rofecoxib (1, 3 or 10
      mg/kg), 2 h before, daily for 7 days, after nerve injury significantly attenuated
      and further delayed the development of hypersensitivity for 21 days following
      nerve injury. These results suggest that the development of hypersensitivity in
      the CCI model is not COX-2 dependent and that the chronic administration of
      naproxen started early before peripheral nerve injury could attenuate the
      development of hypersensitivity.

PMID- 15501313
TI  - Dopaminergic mechanisms in the conditioned and unconditioned fear as assessed by
      the two-way avoidance and light switch-off tests.
AB  - The involvement of dopaminergic mechanisms in fear and anxiety is still unclear.
      Behavioral studies aimed to disclose the involvement of dopamine in anxiety have
      reported anxiolytic-like, anxiogenic-like and lack of effects with the use of
      dopaminergic agonists and antagonists in animal models of anxiety. This work was
      an attempt to contribute to this field by providing evidence that these
      discrepancies may be due to the kind of aversive situation the animals experience
      in these models. The present study examined the effects of a dopaminergic agonist
      apomorphine, a dopaminergic D(1) antagonist SCH 23390 and a D(2) receptor
      antagonist sulpiride on the two-way avoidance response test (CAR) and on the
      switch-off responses to light (SOR). In both tests, learning was assessed by the
      performance of the animals across four blocks of 10 trials in which light was
      paired to footshocks (CAR) or only light was presented to the animals (SOR). The
      obtained data show that rats learn to make a shuttling response to avoid the
      shock in the CAR test and maintain a regular pace of switch-off responses in the
      SOR. While sulpiride and SCH 23390 administrations prevented learning of the
      avoidance responses, apomorphine injections produced a dose-dependent enhancement
      in the conditioned learning in the CAR test. The number of escape responses was
      unchanged by these drugs. In the light-induced switch-off test, apomorphine
      reduced the number of switch-off responses whereas sulpiride increased these
      responses. These findings suggest that the involvement of dopaminergic mechanisms
      in threatening situations depends on the nature of the aversive stimulus.
      Activation of D(1) and D(2) receptors seems to be implicated in the heightened
      aversiveness to conditioned stressful situations, as assessed by the CAR test.
      Thus, blockade of D(1) and D(2) receptors may be necessary for attenuating the
      aversiveness triggered by these conditioned fear stimuli. In contrast, mechanisms
      mediated by D(2) receptors seem to be involved in the setting up of adaptive
      responses to innate fear reactions. Therefore, the signal of the modulatory
      dopaminergic mechanisms on defensive behavior will depend on the type of
      emotional stimuli triggering the coping reaction.

PMID- 15501314
TI  - Role of muscarinic and nicotinic cholinergic receptors in an experimental model
      of epilepsy-induced analgesia.
AB  - The blockade of GABA-mediated Cl(-) influx with pentylenetetrazol (PTZ) was used
      in the present work to induce seizures in animals. The neurotransmission in the
      postictal period has been the focus of many studies, and there is evidence
      suggesting antinociceptive mechanisms following tonic-clonic seizures in both
      animals and men. The aim of this work was to study the involvement of
      acetylcholine in the antinociception induced by convulsions elicited by
      peripheral administration of PTZ (64 mg/kg). Analgesia was measured by the tail
      flick test in eight albino Wistar rats per group. Convulsions were followed by
      significant increases in tail-flick latencies (TFLs) at least for 120 min of the
      postictal period. Peripheral administration of atropine (0.25, 1 and 4 mg/kg)
      caused a significant dose-dependent decrease in the TFL in seizing animals, as
      compared to controls. These data were corroborated by peripheral administration
      of mecamylamine, a nicotinic cholinergic receptor blocker, at the same doses
      (0.25, 1 and 4 mg/kg) used for the muscarinic cholinergic receptor antagonist.
      The recruitment of the muscarinic receptor was made 10 min postconvulsions and in
      subsequent periods of postictal analgesia, whereas the involvement of the
      nicotinic cholinergic receptor was implicated only after 30 min postseizures. The
      cholinergic antagonists caused a minimal reduction in body temperature, but did
      not impair baseline TFL, spontaneous exploration or motor coordination in the
      rotarod test at the maximal dose of 4 mg/kg. These results indicate that
      acetylcholine may be involved as a neurotransmitter in postictal analgesia.

PMID- 15501315
TI  - The effects of angelica essential oil in three murine tests of anxiety.
AB  - The effects of angelica essential oil in three assays predictive of anxiolytic
      activity in male mice were studied, with diazepam as a positive anxiolytic
      control. In the elevated plus-maze test, compared to the positive control
      diazepam, angelica essential oil (30.0 mg/kg, PO) had a modest anxiolytic-like
      effect (increased the percentage of open-arm time and reduced the percent
      protected head dips). In the light/dark test, angelica essential oil (30.0 mg/kg)
      prolonged the time spent in the light area without altering the locomotor
      activity of the animals. In the stress-induced hyperthermia test, 60 and 70 min
      after drug administration, rectal temperature was measured twice, angelica
      essential oil at the dose of 30.0 mg/kg inhibited stress-induced hyperthermia.
      Thus, these findings indicate that angelica essential oil, as does diazepam,
      exhibits an anxiolytic-like effect. Further studies will be required to assess
      the generality of the present findings to other species and behavioural
      paradigms.

PMID- 15501316
TI  - Circulating androgens enhance sensitivity to testosterone self-administration in
      male hamsters.
AB  - Young adult men are more likely to abuse steroids than individuals with low
      testosterone, including women, boys and older men. This suggests that circulating
      testosterone may enhance sensitivity to exogenous androgens. This hypothesis was
      tested using intracerebroventricular (i.c.v.) testosterone self-administration in
      orchidectomized males without testosterone (Orchx, n=8) and in orchidectomized
      males with chronic physiologic testosterone replacement (Orchx+T, n=8). Beginning
      1 week after surgery, hamsters self-administered testosterone for 4 h/day in
      operant chambers at three doses (0.1, 1.0 and 2.0 microg/microl), each for 8
      days. Afterwards, testosterone was replaced with vehicle for 8 days to test
      extinction. At 1.0 and 2.0 microg/microl, Orchx+T and Orchx males self
      administered similar amounts of testosterone. However, at 0.1 microg/microl
      testosterone, only Orchx+T males showed a significant preference for the active
      nose-poke (Orchx+T active: 35.1+/-8.4 responses/4 h [mean+/-S.E.M.] vs. inactive:
      16.5+/-1.7 responses/4 h, p<0.05; Orchx active: 16.7+/-4.9 responses/4 h vs.
      inactive: 13.5+/-3.1 responses/4 h, p>0.05). There was little change in operant
      behavior during extinction in Orchx+T males. However, when vehicle replaced
      testosterone, Orchx males extinguished their preference for the active nose-poke
      hole by day 6. These results support our hypothesis that circulating androgens
      enhance sensitivity to testosterone self-administration.

PMID- 15501318
TI  - Curing depth of (polyacid-modified) composite resins determined by scraping and a
      penetrometer.
AB  - OBJECTIVES: The present study aimed to compare the curing depth of polyacid
      modified composite resins (PAM-C) and some representative composite resins as a
      function of shade and post-cure using a scraping method and a penetrometer.
      METHODS: The curing depth of the PAM-C Hytac, F2000, Glasiosite, Dyract, Dyract
      AP, and Compoglass F and of the composite resins Durafill VS and Z100 were
      determined for shade A2 and A4 using a scraping method based on ISO 4049:2000 and
      a digital penetrometer. Samples were light-cured (800 mW/cm2 at 40 s) in bulk in
      split stainless steel molds. Immediately after light-curing or after a 24 h post
      cure, the height of the cylinder of cured material was measured and taken as the
      curing depth. RESULTS: For both test methods, the curing depth was independent of
      post-cure (P > or = 0.05) but differed significantly among materials and shade
      (P<0.001). Moreover, there was a significant interaction between the latter
      (P<0.001). Regression analysis generally demonstrated that there was no
      significant systematic or proportional difference between the test methods. The
      curing depths of the PAM-C F2000 and Glasiosite were comparable to that of the
      hybrid composite Z100, but greater than the curing depth of the microfilled
      composite Durafill VS. The PAM-C Dyract AP, Dyract, Compoglass F and Hytac had a
      curing depth smaller than that of the microfilled composite. SIGNIFICANCE: The
      scraping method based on ISO 4049:2000 and a digital penetrometer give comparable
      curing depths for PAM-C. The curing depth greatly varies among the materials and
      can be considerably smaller than that of a microfilled composite resin. Shade A2
      results in significantly greater values for the curing depth compared to shade
      A4, the effect depending quantitatively on the formulation of the material.

PMID- 15501317
TI  - Shear bond strength of different types of luting cements to an aluminum oxide
      reinforced glass ceramic core material.
AB  - OBJECTIVE: The aim of this study was to find the optimal choice of luting cement
      to Synthoceram, an aluminum oxide-reinforced glass ceramic material. The bond
      strength of five different commercial luting cements to the ceramic material was
      evaluated. The effect of surface treatments, etching, sandblasting, silanizing,
      and combinations of these treatments was also investigated. METHODS: Shear bond
      strength tests were performed using the ceramic material as substrate with each
      of the luting cements. Cements rods were prepared on pre-treated ceramic
      surfaces. The shear bond strength was determined 24 h after cementation. The
      effect of surface treatments: etching, sandblasting, and sandblasting followed by
      etching, respectively, on the morphology of the material, was investigated with
      SEM. RESULTS: The shear bond strength increases significantly from Ketac Cem,
      Rely X Luting, Fuji Plus, Panavia F to Xeno Cem. The surface treatments etching
      and/or sandblasting followed by silanization generally provide the highest bond
      strength values. SIGNIFICANCE: Based on the results of this study, the use of
      resin composite based cements is preferred for cementation of an all-ceramic
      restoration with an aluminum oxide-reinforced glass ceramic base. Surface
      treatment of etching and/or sandblasting followed by silanization is recommended.

PMID- 15501319
TI  - Influence of the powder/liquid ratio on the properties of zinc oxide-eugenol
      based root canal sealers.
AB  - OBJECTIVE: The purpose of this study was to investigate the effects of
      modifications of the powder/liquid ratio by endodontists on the physical
      properties recommended by ISO standards as well as on other clinically relevant
      properties of zinc oxide-eugenol-based root canal sealers. METHODS: The
      powder/liquid ratio of two zinc oxide-eugenol-based root canal sealers
      (Cortisomol and Pulp Canal Sealer EWT) was recorded by 10 endodontists. The
      materials, prepared according to the different consistencies, were tested
      according to ISO standards to evaluate their physical properties. Their sealing
      efficiency and the release of eugenol were also evaluated on 20 single rooted
      teeth. RESULTS: Some results varied according to the material. Nevertheless, for
      both cements, an increased powder/liquid ratio led to a decreased flow, an
      increased radiopacity and a decreased amount of eugenol released. The variations
      in the powder/liquid ratio did not influence the dimensional changes and the
      apical leakage of both cements. SIGNIFICANCE: Variations in the powder/liquid
      ratio of zinc oxide-eugenol-based root canal sealers have a limited influence on
      the properties of the sealers. The endodontists can prepare the zinc oxide
      eugenol-based root canal sealers at their chosen consistency according to the
      filling technique they use.

PMID- 15501320
TI  - Surfactants as part of a combined etchant and activator solution prior to the use
      of an anaerobic adhesive.
AB  - OBJECTIVES: The objectives of this experiment were to determine whether the
      incorporation of a surfactant into a combined etchant and activator solution
      would further promote the polymerization of an anaerobic adhesive. METHOD:
      Stainless steel attachments were bonded to human enamel using an anaerobic
      adhesive. In each case the enamel was etched and activated using a solution of
      37% o-phosphoric acid containing copper (II) sulphates or chlorides with one of
      three surfactants also within the solution. After bench curing, the specimens
      were shear bond tested to failure and the load at debond recorded in each case.
      RESULTS: The results were analysed using Kaplan-Meier survival probabilities and
      log-rank tests along with a multiple comparison test, using Bonferroni's method.
      CONCLUSIONS: Under the conditions of this experiment the addition of a surfactant
      to a combined etchant activator solution of 37% o-phosphoric acid and either
      copper (II) sulphate or copper (II) chloride, prior to the use of an anaerobic
      adhesive can have a significant effect on measured force to debond. However, with
      copper (II) sulphate the highest force to debond was observed with the control
      solution without a surfactant. With copper (II) chloride the surfactant Tween 20
      increased the observed force to debond but the effect was not statistically
      significant. SIGNIFICANCE: Although it is possible to render the enamel surface
      both retentive and active towards anaerobic adhesives using a combined etchant
      and activator solution, the addition of a surfactant has little or no beneficial
      effect.

PMID- 15501321
TI  - Effect of the applied load on surface contact fatigue of dental filling
      materials.
AB  - OBJECTIVE: The purpose of this study was to investigate the effect of the applied
      load in a rolling-ball device on the surface contact fatigue of two dental
      filling materials: a microfilled composite (FA) and a glass ionomer (GFII).
      METHODS: Disk specimens 10 mm diameter by 1.5 mm thick were set into cavities cut
      in plates of PMMA. After setting, the specimens were ground and polished using
      wet-carborundum paper followed by 1 microm alumina and then stored for 24 h in
      water at 23 degrees C. The surface fatigue test was carried out using loads
      ranging from 100 to 500 gf through a ruby ball 2 mm diameter using a rolling-ball
      device. The ball was set to rotate at 720 rpm and a surface profile was
      determined on impressions recorded at regular intervals. Fatigue life was defined
      as the number of cycles to produce a track 5 microm deep and was determined by
      interpolation. Data were statistically analyzed by ANOVA and t-tests at a
      significance level of 0.05. RESULTS: At loads ranging from 200 to 500 gf the
      fatigue life was 0.7-10.6 x 10(5) cycles for FA, and 0.7-4.8 x 10(3) cycles for
      GFII. For both materials the fatigue life was reduced significantly by increasing
      the test load (p<0.05). The surface contact fatigue life for FA was at least 100
      times greater than that for GFII at all loads. SIGNIFICANCE: The rolling ball
      device was confirmed as a simple and meaningful device for the study of surface
      contact fatigue. A microfilled composite is very much more resistant to contact
      fatigue than a glass ionomer.

PMID- 15501322
TI  - Relationship between contraction stress and degree of conversion in restorative
      composites.
AB  - OBJECTIVES: To verify the relationship between contraction stress and degree of
      conversion (DC) in different composites (Filtek Z250, Filtek A110, Tetric Ceram
      and Heliomolar). METHODS: For the contraction stress test, composite (2 mm thick)
      was applied between two 5-mm diameter glass rods, mounted in a tensilometer. DC
      was determined by Infrared Photoacoustic spectroscopy in specimens with similar
      dimensions and geometry, submitted to identical curing conditions. Specimens were
      exposed to different energy densities (4.5, 13.5, 27.0, 54.0 and 108.0 J/cm2) by
      varying exposure time. Contraction stress and DC were recorded 10 min after the
      beginning of photoactivation. Results were analyzed by ANOVA/Tukey's test and
      regression analysis. RESULTS: For contraction stress, the interaction between
      composite and energy density was significant. Stress values ranged between 0.6+/
      0.2 and 2.0+/-0.3 MPa at 4.5 J/cm2, 2.3+/-0.5 and 4.3+/-0.4 MPa at 13.5 J/cm2,
      3.8+/-0.5 and 5.8+/-0.9 MPa at 27.0 J/cm2, 4.2+/-0.8 and 7.9+/-0.9 MPa at 54.0
      J/cm2 and 6.6+/-0.8 and 8.1+/-0.9 MPa at 108.0 J/cm2. Tetric Ceram (39+/-5.8%)
      showed a higher average DC than the other materials. Heliomolar (28+/-5.2%)
      showed an average DC similar to Filtek Z250 (32+/-6.6%) and to Filtek A110 (24+/
      7.5%) regardless of the energy density level. No significant increase in DC was
      observed above 27 J/cm2. CONCLUSIONS: At high energy levels, DC had a tendency to
      level off earlier than contraction stress values. SIGNIFICANCE: Using high energy
      densities may cause a significant increase in stress values, without producing a
      significant increase in conversion.

PMID- 15501323
TI  - Effect of fiber position and orientation on fracture load of fiber-reinforced
      composite.
AB  - OBJECTIVES: The aim of this study was to determine the effect of fiber position
      and orientation on the initial and final fracture loads of fiber-reinforced
      composite (FRC). METHODS: Test specimens made of two indirect particulate
      composites (BelleGlass HP, Kerr, Orange, CA) or (Targis, Ivoclar Vivadent,
      Amherst, NY) were reinforced with ultra high molecular weight polyethylene
      (UHMWPE) fiber ribbon (Connect, Kerr, Orange, CA), woven E-glass fibers (Vectris
      Frame, Ivoclar Vivadent, Amherst, NY) or unidirectional R-glass fibers (Vectris
      Pontic, Ivoclar Vivadent, Amherst, NY). Fibers were placed with different
      positions, orientations or geometry into the rhombic test specimens (2 x 2 x 25
      mm3). Control specimens did not contain fiber reinforcement. The test specimens
      (n=6) were stored in distilled water for 1 week at 37 degrees C before testing in
      a three-point loading test to determine the initial and final fracture load
      values. RESULTS: Initial failure loads varied from 22.6 to 172.1 N. The lowest
      value resulted from one UHMWPE reinforcement fiber located in diagonal
      orientation and the highest from two unidirectional glass fiber reinforcements,
      one located on the tension side and the second on the compression side.
      SIGNIFICANCE: Position and fiber orientation influenced the load to initial and
      final failure, and specimen deflection. Tension side reinforcement was most
      effective in increasing the load to initial and final fracture.

PMID- 15501324
TI  - Fracture behavior of lithia disilicate- and leucite-based ceramics.
AB  - OBJECTIVE: This study was designed to characterize the fracture behavior of
      ceramics and test the hypothesis that variation in strength is associated with a
      variation in fracture toughness. METHODS: The following four groups of 20 bar
      specimens (25 x 4 x 1.2 mm) were fabricated (ISO standard 6872): E1, a hot
      pressed leucite-based core ceramic (IPS Empress); E2, a hot-pressed lithia-based
      core ceramic (IPS Empress 2); ES, a hot-pressed lithia-based core ceramic
      (Experimental); and GV, a glass veneer (IPS Empress2 body). Specimens were
      subjected to four-point flexure loading in 37 degrees C distilled water.
      Fractographic analysis was performed to determine the fracture origin (c) for
      calculation of fracture toughness (KIC). Weibull analysis of flexure strength
      (sigma) data was also performed. RESULTS: Differences in mean sigma and KIC were
      statistically significant for E1 and GV (p<0.05). These differences are
      associated with processing effects and composition. SIGNIFICANCE: The higher mean
      sigma and KIC values of E2 and ES core ceramics suggest potentially improved
      structural performance compared with E1 although the Weibull moduli of E1 and E2
      are the same.

PMID- 15501325
TI  - Bonding of an auto-adhesive luting material to enamel and dentin.
AB  - OBJECTIVES: The objectives of this study were (1) to assess the bonding
      performance of a new auto-adhesive cement (RelyX Unicem, 3M ESPE) to enamel and
      dentin, using a standard micro-tensile bond strength (microTBS) test set-up, and
      (2) to evaluate the interaction of this material with dentin by means of high
      resolution electron microscopy. METHODS: The microTBS of RelyX Unicem with and
      without prior acid etching was determined to enamel and dentin after 24 h of
      water storage and compared to the bonding effectiveness of the control cement
      (Panavia-F, Kuraray). In addition, diamond-knife cut interfaces of RelyX Unicem
      and Panavia-F bonded to dentin were examined using field-emission scanning (Fe
      SEM) and transmission electron microscopy (TEM). RESULTS: The microTBS of RelyX
      Unicem to enamel was significantly lower than that of the control cement, whereas
      no significant difference was found when both cements were bonded to dentin. Acid
      etching prior to the application of RelyX Unicem raised the enamel microTBS to
      the same level as that of the control, but was detrimental for the dentin bonding
      effectiveness. The latter must be attributed to inadequate infiltration of the
      collagen mesh as revealed by Fe-SEM and TEM. Morphological evaluation
      additionally revealed that RelyX Unicem only superficially interacted with enamel
      and dentin, and that application using some pressure is required to ensure close
      adaptation of the cement to the cavity wall. SIGNIFICANCE: (1) RelyX Unicem
      should always be applied with some pressure, to ensure that the relatively high
      viscous cement intimately adapts to the cavity wall; (2) The cement only
      interacted superficially with dentin and enamel; (3) The best bonding
      effectiveness with this new auto-adhesive cement was obtained by selectively acid
      etching enamel prior to luting.

PMID- 15501326
TI  - Effect of mixing method on the porosity of encapsulated glass ionomer cement.
AB  - OBJECTIVE: To observe cement specimens mixed by various methods non-destructively
      using microfocus computerized tomography (micro-CT) and to evaluate the effect of
      mixing method on porosity. METHOD: Five glass ionomer cements were used: two were
      hand-mixed and three were encapsulated. The latter were mixed either by shaking
      or rotating. Fifteen cylindrical specimens were prepared for each material by
      each mixing method and stored in distilled water at 37 degrees C until testing.
      The specimens were observed and analyzed using micro-CT. 201 sliced images were
      obtained horizontally along the length of the specimens. Three-dimensional
      reconstructions were made and the sizes, numbers and total volume ratio of
      bubbles in the specimens were calculated. RESULTS: Mixing method had a
      significant effect on porosity (P<0.05). For the luting/lining cement, mechanical
      mixing produced a significantly higher porosity (P<0.05). For the restorative
      cement, there were only small differences in porosity between specimens mixed by
      the two methods. More large bubbles were detected in specimens mixed mechanically
      than by hand for the fluid material. This suggested that for low-viscosity
      materials bubbles may combine until a certain viscosity is reached during
      setting. SIGNIFICANCE: The strength of glass ionomer cement is affected by
      incorporated porosity and this depends on the mixing method. For low-viscosity
      cements, hand-mixing is favored in order to reduce porosity and increase
      strength, but this is not generally applicable to high-viscosity cements.

PMID- 15501327
TI  - Towards the elucidation of shrinkage stress development and relaxation in dental
      composites.
AB  - OBJECTIVE: Although various photo-curing techniques aiming to partially relieve
      the shrinkage stress by flow have been proposed and investigated, the direct
      monitoring and observation of stress relaxation behavior received little
      attention. In this study, the elucidation of stress relaxation behavior and its
      impact on the overall stress development were investigated. METHODS: A novel
      experimental set-up capable of real-time, simultaneous shrinkage stress and
      double bond conversion measurements on the same sample was utilized. The coupled
      shrinkage stress and conversion for specimens of a barium glass filled Bis
      GMA/TEGDMA composite were continuously monitored during and after irradiation for
      various intervals (2, 3, 6, 10 and 60s). RESULTS: Specimens irradiated for 60s
      reached the highest conversion (67.9+/-1.2%) and shrinkage stress (2.9+/-0.1
      MPa). Shrinkage stress relaxation phenomena were only observed prior to
      vitrification, which only applied to specimens partially cured for 2 or 3 s;
      specimens irradiated for 2 s exhibit the largest capability to relieve stress
      (approximately 40%). However, to achieve this a much longer post-cure stress
      relaxation time is required as compared to clinically practical time scales. For
      specimens irradiated for 6, 10 or 60 s, the majority of the shrinkage stress is
      developed during and after the vitrification stage, and no appreciable stress
      relaxation can be observed. SIGNIFICANCE: Although stress relaxation prior to
      vitrification stage has been observed, this study revealed that it did not
      provide a significant benefit towards the reduction of overall shrinkage stress
      since, to achieve clinically relevant conversion, the majority of the shrinkage
      stress is developed during and after the vitrification stage, which does not
      permit stress relaxation on the time scales used in this study.

PMID- 15501328
TI  - Porosity evaluation and pore size distribution of a novel directly placed ceramic
      restorative material.
AB  - OBJECTIVES: The aim of this in vitro study was to compare porosity, i.e. voids or
      pores due to placement, of a new directly placed ceramic restorative material
      (DoxaDent, Doxa Certex AB, Uppsala, Sweden) to a glass ionomer (Fuji IX, GC
      Corporation, Tokyo, Japan), a hybrid composite control (Filtek Z250, 3M ESPE St
      Paul, MN, USA) and an amalgam control (Tytin, Kerr Orange, CA, USA). Pore
      distribution and size were determined for each material tested. METHODS:
      Standardized MOD preparations (one operator) on 20 extracted human molars had
      gingival margins located above and below the CEJ. Restored teeth (5
      teeth/material) were sectioned in mesio-distal directions (two sections/tooth;
      n=10/group). Sections were polished through 1 microm Al2O3 abrasive. Porosity
      levels and size distributions were measured using SEM. Effects of different
      gingival extensions of inter-proximal boxes on porosity levels and distributions
      were investigated (mesial, occlusal, and distal regions). RESULTS: No MOD region
      was free of pores. Porosity in mesial, occlusal and distal boxes, respectively,
      for each restorative material were (vol%): Tytin: 1.3(0.9), 2.9(2.1), and
      2.9(1.4); Filtek Z250: 2.6(1.0), 2.9(1.0), and 2.6(0.8); Fuji IX: 8.8(1.9),
      7.9(1.7), and 7.7(1.8); Doxadent: 13.0(1.8), 12.4(1.7), and 11.5(1.4). Overall
      porosity ranged from 2.4(0.9)% for Kerr Tytin, 2.7(0.7)% for Filtek Z250,
      8.0(1.1)% for GC Fuji IX, and 12.3(1.1)% for Doxadent. There was no difference
      between Z250 composite and Tytin amalgam, but differences existed between them
      with Fuji IX and Doxadent. No statistically significant difference (p>0.05) in
      porosity occurred among different restoration regions (mesial, distal and
      occlusal box) for any material. Total porosity levels for different measurement
      methods (point counting versus direct counting) were remarkable consistent
      (p>0.05). SIGNIFICANCE: Based on results of this limited study, the new directly
      placed ceramic restorative material (Doxadent) contains significantly (p<0.05)
      higher bulk porosity levels than both amalgam and composite. This may explain the
      lower than expected mechanical property values reported in other studies.

PMID- 15501329
TI  - Multiresistant acinetobacter in the UK: how big a threat?

PMID- 15501330
TI  - A prevalent, multiresistant clone of Acinetobacter baumannii in Southeast
      England.
AB  - A multiresistant clone of Acinetobacter baumannii was identified in 24 hospitals
      in the UK, predominantly in the London area, over a period of three years.
      Isolates were characterized by distinctive ApaI macrorestriction profiles, as
      resolved by pulsed-field gel electrophoresis (PFGE), which all clustered within
      80% similarity using a 1% band position tolerance setting. The first isolates
      identified were received by the reference laboratories in April 2000, and by June
      2003, a total of 375 isolates with similar PFGE profiles from 310 patients from
      24 hospitals had been received. The isolates originated mainly from sputum and
      wound specimens, with the majority from patients in intensive care units.
      Amplified fragment length polymorphism analysis of a subset of isolates showed
      that they clustered closely, supporting the PFGE results. All the isolates tested
      were highly resistant to ampicillin, piperacillin, piperacillin/tazobactam,
      ceftazidime, cefotaxime, gentamicin and ciprofloxacin, and most isolates were
      carbapenem resistant. Amikacin sensitivity varied from susceptible [minimum
      inhibitory concentration (MIC) <or= 4 mg/L] to highly resistant (MIC >256 mg/L).

PMID- 15501331
TI  - Control of methicillin-resistant Staphylococcus aureus outbreak involving several
      hospitals.
AB  - This population-based, retrospective, cohort study describes a large methicillin
      resistant Staphylococcus aureus (MRSA) epidemic caused by one strain (E1) in the
      greater Helsinki region. The epidemic comprised 210 cases at several hospitals,
      but was finally controlled. The study period ranged from June 1991 to December
      2000. The epidemic peaked in 1993-1995 with 143 cases (68% of total cases). From
      August 1993, all MRSA-positive cases at the eight municipal hospitals were
      isolated and barrier nursed. Contacts were cohorted and screened for MRSA
      colonization. Decolonization treatment was administered to some chronic carriers.
      MRSA cases and contacts were identified in the joint patient register of the
      municipal hospitals from August 1993. The annual incidence of MRSA E1 in Helsinki
      City area per 100,000 inhabitants rose from 0.2 in 1991 to 13.6 in 1994. It
      decreased from 1995, reaching 0.7 per 100,000 in 2000. A jointly agreed policy on
      MRSA and timely co-operation between all units were essential for control of this
      epidemic.

PMID- 15501332
TI  - Use of antibiotics in hospitals in south-western France.
AB  - Data on the use of antibiotics were collected by means of a questionnaire from 49
      hospitals in south-western France. Use was expressed as a usage density rate:
      number of defined daily doses (DDDs) per 1000 patient-days. The average use of
      antibiotics amounted to 402 DDDs per 1000 patient-days and varied between 60 and
      734. In acute-care wards, the amount of antibiotic use increased with the size of
      the hospital: 461 DDDs per 1000 patient-days for group A (<100 beds), 510 DDDs
      per 1000 patient-days for group B (more than 100 and less then 300 beds) and 676
      DDDs per 1000 patient-days for group C (>300 beds). The rate of use differed
      among different types of hospital areas and varied from 58 for psychiatry
      departments to more than 1273 DDDs per 1000 patient-days for the infectious
      diseases departments. Broad-spectrum penicillins were the most frequently
      prescribed antibiotics. Fluoroquinolone and third-generation cephalosporin use
      were relatively uniform in the three size categories. This study shows that it is
      possible for a hospital to benchmark its consumption with other hospitals that
      are similar in size. In this way, surveillance of antibiotic use can aid
      hospitals in targeting infection control efforts.

PMID- 15501333
TI  - Professionals' awareness of operational antibiotic prescribing controls in UK NHS
      hospitals.
AB  - In recent years, there have been increasing recommendations for multidisciplinary
      collaboration between clinical pharmacists and medical microbiologists in an
      attempt to control the quality (and quantity) of antibiotic prescribing. A
      questionnaire addressing the utilization of antibiotic prescribing controls was
      sent to the chief pharmacist and medical microbiologist in UK NHS hospitals.
      Responses were received from both the chief pharmacist and the medical
      microbiologist employed in the same hospital from 83 hospitals (a 30% response
      rate from two independent studies). A high level of disagreement and poor
      awareness was identified between the interprofessional staff groups regarding the
      existence of antibiotic formulary (with disagreement between the two groups, or
      not known by one or both respondents, in 46% of the paired hospitals, N = 38) and
      guideline documents (13%, N = 11), performance of antibiotic prescribing audits
      (40%, N = 33), and whether pharmacists (52%, N = 43) and medical microbiologists
      (77%, N = 64) monitored physician compliance with antibiotic prescribing control
      documents. This study has identified poor knowledge of the existence of basic
      antibiotic prescribing control mechanisms and the role of professional
      colleagues. It is suggested that there is some way to go before 'Agenda for
      Change' principles of flexible and collaborative roles are met.

PMID- 15501334
TI  - Genotyping analysis of colonizing candidal isolates from very-low-birthweight
      infants in a neonatal intensive care unit.
AB  - To analyse the relatedness of colonizing candidal isolates from very-low
      birthweight infants hospitalized in a neonatal intensive care unit (NICU), we
      prospectively collected 86 candidal isolates from 20 infants, including 67
      isolates of Candida albicans from 15 infants, 17 isolates of Candida parapsilosis
      from five infants and two isolates of Candida glabrata from one infant, who also
      had C. albicans colonization, over a one-year period. All 86 isolates were
      genotyped by infrequent-restriction-site polymerase chain reaction (IRS-PCR) and
      electrophoretic karyotyping (EK) with pulsed-field gel electrophoresis. A total
      of 15 genotypes were identified by IRS-PCR and 12 genotypes by EK. Some infants
      shared a common genotype. From a single infant, an identical genotype was found
      in 11 of 13 cases where at least two isolates of same Candida species were
      available for genotyping analysis, regardless of anatomical site, how many
      isolates were recovered or how many times. Should an infant harbour a candidal
      strain, they may harbour this strain at multiple sites and for a prolonged
      period.

PMID- 15501335
TI  - Medical procedures and the risk of iatrogenic hepatitis C infection: case
      controlled study in north-eastern Poland.
AB  - Many hepatitis C virus (HCV)-infected individuals do not have any obvious risk
      factors and one of the putative sources of infection may be inadvertent exposure
      to infected blood or body fluids in the clinical setting. The aim of this study
      was to assess the role of medical procedures in transmission of hepatitis C in
      north-eastern Poland. In total, 194 patients with chronic hepatitis C were
      eligible for the study. The control group consisted of 275 age- and sex-matched
      individuals. Patients with a history of intravenous drug use were excluded. On
      multivariate analysis, transfusions [odds ratio (OR) = 3.7, 95% confidence
      interval (CI) 2.2-6.3], minor surgery (OR = 3.2, 95% CI 1.5-6.7) and dental care
      (OR = 2.3, 95% CI = 1.4-4.0) were independently associated with HCV infection. We
      conclude that apart from transfusion, minor medical procedures and dental care
      may carry a significant risk of hepatitis C infection. Improvements in basic
      hygiene routines and strict adherence to universal precautions may be essential
      to prevent iatrogenic transmission of the infection.

PMID- 15501336
TI  - Management of inpatients exposed to an outbreak of severe acute respiratory
      syndrome (SARS).
AB  - This is a prospective observational study of a cohort of inpatients exposed to a
      severe acute respiratory syndrome (SARS) outbreak. Strict infection control
      policies were instituted. The 70 patients exposed to the SARS outbreak were
      isolated from the rest of the hospital. They were triaged, quarantined and
      cohorted in three open plan wards. Selective isolation was carried out
      immediately when symptoms and signs suspicious of SARS manifested clinically. The
      patients' ages ranged from 21 to 90 years and 56% had surgery before the
      quarantine. Sixteen patients with unexplained fever during the period of
      quarantine were isolated, seven of whom were eventually diagnosed with probable
      SARS. The crude incidence of SARS in our cohort was 10%. The SARS case fatality
      was 14%. No secondary transmission of the SARS virus within the cohort was
      observed. Strict infection control, together with appropriate triaging, cohorting
      and selective isolation, is an effective and practical model of intervention in
      cohorts exposed to a SARS outbreak. Such a management strategy eases the logistic
      constraints imposed by demands for large numbers of isolation facilities in the
      face of a massive outbreak.

PMID- 15501337
TI  - Needlestick and sharps injuries among nurses in the healthcare sector in a city
      of western Turkey.
AB  - The aims of this study were to determine the rate of bloodborne infections after
      needlestick and sharps injuries in nurses at work, to estimate the number of
      vaccinations administered, and to assess whether universal precautions were being
      followed. The study involved 289 nurses working in five hospitals and six primary
      healthcare centres. Between 1 April 2002 and 31 June 2002, a total of 139
      practising nurses were included in the study following a needlestick or sharps
      injury. The results of completed questionnaires were collated, and Chi-squared
      test was used for analysis. The rate of hollow-bored needle-related injuries was
      76.2% (106/139). Most nurses (69.1%) did not report any details of their injuries
      and 32.4% (45/139) of nurses had not been vaccinated against hepatitis B virus
      (HBV). Only 5.3% of the nurses who responded to the compliance question indicated
      that they always complied with universal precautions. Of 139 nurses, 1.4% and
      7.9% showed evidence of HBV infection and hepatitis C virus (HCV) infection,
      respectively. All those who had hepatitis B were aged 30 years or under, whereas
      most of those who were anti-HCV positive (81.8%) were over 30 years old (P <
      0.05). Nurses working in the Turkish healthcare sector are frequently exposed to
      bloodborne infections. Precautions and protection from needlestick and sharps
      injuries are important in preventing infection of nurses. Education about the
      transmission of bloodborne infections, vaccination and post-exposure prophylaxis
      must be implemented. Further investigations are warranted to elucidate the risk
      to nurses of contracting these potentially serious infections.

PMID- 15501338
TI  - Is biofilm accumulation on endoscope tubing a contributor to the failure of
      cleaning and decontamination?
AB  - We predicted that biofilm would form on surfaces of endoscope tubing in contact
      with fluids, and may be difficult to remove by current washing procedures. Its
      presence may protect micro-organisms from disinfectant action and contribute to
      failure of decontamination prior to re-use. Tubing samples removed from 13
      endoscopes that had been sent to an endoscope-servicing centre were examined for
      the presence of biofilm and bacteria by scanning electron microscopy. Biological
      deposits were present on all samples tested. Biofilm (bacteria plus
      exopolysaccharides matrix) was present on the suction/biopsy channels of five of
      13 instruments, and was very extensive on one of these. Bacteria and
      microcolonies were often but not necessarily associated with surface defects on
      the tubing. All 12 air/water channels examined showed biofilm, and this was
      extensive on nine samples. Routine cleaning procedures do not remove biofilm
      reliably from endoscope channels, and this may explain the unexpected failure of
      decontamination encountered in practice despite good adherence to infection
      control guidelines.

PMID- 15501339
TI  - Source of bacterial shedding in laminar flow theatres.
AB  - In a previous unpublished observation, unacceptably high bacterial counts,
      presumably due to shedding episodes, occurred in two of 56 (3.57%) slit-air
      samples during arthroplasty surgery in a laminar flow operating theatre. The
      isolates matched those cultured from swab samples taken from the skin of one of
      the surgeons's foreheads on each of the two occasions. These findings occurred
      despite scrub staff wearing standard occlusive gowns, hats and masks with visors.
      In order to localize the potential source of such shedding more accurately, 20
      members of theatre staff underwent anonymous microbiological swabbing from the
      facial areas not covered by theatre clothing, namely their foreheads, eyebrows
      and ears. These swabs were cultured and the growths were compared statistically.
      Significantly more colonies were cultured from swabs taken from the theatre
      staff's ears (P = 0.047, Freidman's test) compared with the other two facial
      areas studied. These data support the use of exhaust helmets in arthroplasty
      surgery, or at least mandatory coverage of the ears with theatre hats for scrub
      staff.

PMID- 15501340
TI  - In situ endoluminal brushing: a safe technique for the diagnosis of catheter
      related bloodstream infection.
AB  - We assessed the safety of the endoluminal brush technique for the in situ
      diagnosis of central-venous-catheter (CVC)-related bloodstream infection (CRBSI).
      The endoluminal brush was used to investigate patients with suspected CRBSI by
      sampling the CVC lumen to within 3-5 cm of the catheter tip (the brush was kinked
      to mark the length required). Quantitative peripheral blood cultures were taken 1
      min pre-brushing and 1 min and 1h post-brushing. In addition, a 1 mL sample of
      through-catheter blood was aspirated immediately pre- and post-brushing, and
      aliquots were directly plated on to blood agar to determine the load of CVC
      associated bacteria. After CVC removal, catheter tips were sent for culture using
      the Maki roll and modified Cleri flush techniques. Of 139 suspected cases, 61
      (45%) had confirmed episodes of CRBSI. No patients experienced fever or rigors,
      or had evidence of embolic phenomena after CVC endoluminal brushing. There was no
      difference overall in pre-brushing and 1-min post-brushing peripheral blood
      bacterial counts (P < 0.702). Peripheral and CVC blood bacterial counts were
      significantly reduced 1h post-brushing (P < 0.03 and P < 0.001, respectively),
      possibly due to removal of endoluminal biomass. The endoluminal brush technique
      can be safely used to diagnose CRBSI without the need for CVC removal, provided
      that the brush is not allowed to protrude beyond the tip of the catheter.

PMID- 15501341
TI  - Methicillin-resistant Staphylococcus aureus infections and colonizations in an
      intensive care unit apparently stopped by environmental factors.

PMID- 15501342
TI  - Laboratory evaluation of selective mannitol broth for MRSA screening.

PMID- 15501343
TI  - The effectiveness of training and taste testing when using respirator masks.

PMID- 15501344
TI  - Impact of mandatory Clostridium difficile surveillance on diagnostic services.

PMID- 15501345
TI  - Nosocomial infection: hospital infection surveillance and control.

PMID- 15501346
TI  - [Non-lipid effects of statins in atherosclerosis].

PMID- 15501347
TI  - [Effect of smoking on the effectiveness of antimalarial drugs for cutaneous
      lesions of patients with lupus: assessment in a prospective study].
AB  - PURPOSE: Smoking has been involved in the failure of antimalarial therapy in
      patient with chronic or subacute erythematosus lupus. METHODS: We report a
      prospective study of 26 patients with chronic, subacute or systemic erythematosus
      lupus who were treated with antimalarials. Several variables including smoking
      are compared in responders and non-responders. RESULTS: Despite the reduced
      number of patients study that does not permit to allow significative results, it
      seems that among responders and non-responders, in other respects comparables,
      there is no difference in the presence of smoking, its quantity or its duration.
      CONCLUSION: The significance of molecular interactions between some components of
      tobacco and antimalarials have still to be established.

PMID- 15501349
TI  - [Statins and cerebral and cardiovascular risk in elderly people].
AB  - INTRODUCTION: The rationale for the treatment of hypercholesterolemia in the
      elderly is less clear than in middle-aged patients because of several conceptual,
      epidemiological, economical facts, a higher prevalence of polypathology and a
      weaker relation between hypercholesterolemia and cardiovascular risk when age
      increases. CURRENT KNOWLEDGE AND KEY POINTS: However, cardiovascular events
      stroke and myocardial infarction occur mainly in people aged more than 65 years.
      The data of recent randomised clinical trials have demonstrated that the use of
      statins in the elderly remained associated to a reduced all-cause mortality,
      cardiovascular mortality and stroke. Statins were effective in elderly with
      average LDL-cholesterol in primary and secondary prevention trials. The drug
      tolerance was as good as in middle-aged patients. However, convincing data
      concerning subjects over 80 are lacking. CONCLUSION: On the basis of disponible
      data it may be considered that statins are useful in older persons with a serum
      LDL cholesterol level above 1.3 g/l and or a high cardiovascular risk, with or
      without cardiovascular disease, when their life expectancy is consequent.

PMID- 15501348
TI  - [Giant cell arteritis and polymyalgia rheumatica: influence of past pregnancies?
      The GRACG multicenter case control study].
AB  - BACKGROUND: The overprevalence of giant cell arteritis (GCA) and polymyalgia
      rheumatica (PMR) in women remains unexplained. Microchimerism pathogenicity has
      been discussed in some systemic diseases. We tested history of pregnancy as a
      risk factor for GCA. METHODS: Prospective, multicenter case-control study with
      multiple, age-matched, control groups. Patients have been included in 40
      different centers. The first control group has been randomly selected in the
      general population, consecutive hospitalized patients in two geographically
      distant departments of internal medicine made up the second and third ones.
      RESULTS: Three hundred and fifteen patients (249 GCA and 66 PMR), 242 general
      population controls, 333 in the first hospitalized control group, and 355 in the
      second, have been included in the 1991-1998 period. Pregnancy has been constantly
      protective against GCA/PMR (Wilcoxon rank sum test: P = 0.0001, 0.0005, and
      0.054, respectively, for the three control groups), more particularly for parity
      equal or greater than 4 (OR = 0.32, 95% CI: 0.18-0.57, P = 0.00003; OR = 0.44,
      95% CI: 0.26-0.74; P = 0.0009, and OR = 0.42; 95% CI: 0.25-0.71, P = 0.0006,
      respectively). In multivariate analysis, risk for GCA on pre-existing
      degenerative, vascular disease is decreased by half for each pregnancy (OR =
      0.49, 95% CI = 0.27-0.90, P = 0.022). CONCLUSION: Contrary to the initial
      hypothesis, multiparity is a protective factor against GCA. Mechanism is unknown.

PMID- 15501350
TI  - [Menopause in 2004: "hormone replacement therapy" is not what it used to be
      anymore].
AB  - PURPOSE: The data concerning post-menopausal hormone replacement therapy (HRT)
      were recently completely modified. The aim of this review is to present the last
      studies about post-menopausal HRT and to describe new alternatives to this
      treatment. CURRENT KNOWLEDGE AND KEY POINTS: In May 2002, the women's health
      initiative (WHI) trial of post-menopausal HRT was interrupted earlier than
      expected. The studied hormonal formulation in this arm of the WHI trial was the
      association of conjugated equine estrogens and medroxyprogesterone. The reason
      for termination was an increased risk of breast cancer and myocardial infarction
      in the hormone-therapy group. Later, reports confirmed that this type of HRT
      could not be used any more for the primary prevention of coronary heart disease
      even if the absolute risk remained low. There is an increased risk for venous
      thromboembolism with post-menopausal estroprogestative replacement. This risk
      does not seem to exist with transdermal estrogens. The other WHI findings
      concerned the lack of protection against dementia and cognitive decline. On the
      contrary, osteoporotic hip fractures and colorectal cancers were reduced in the
      treated group. In April 2004, the estrogen only arm of the same WHI study was
      also prematurely interrupted because of an increase in the incidence of stroke.
      The risk of breast cancer was on the contrary not increased after 6.8 years,
      raising the question of the eventual role of progestins. PERSPECTIVES: The impact
      of the WHI trial on clinical practice was very important since then. The "Agence
      Francaise de securite sanitaire des produits de sante" (AFSSAPS) edited in May
      2004 a public recommendation limiting indication for HRT to patients with severe
      climacteric symptoms. The treatment must now be prescribed for the shortest time
      and at the minimal dose. The patient has to be precisely informed about the risks
      with HRT and the practitioner has to re-evaluate his prescription annually.
      Hormonal or non-hormonal alternatives have also to be considered as
      phytoestrogens and tibolone for hot flashes, and raloxifene and diphosphonates
      for osteoporosis prevention. In any case, a healthy diet, exercise and smoking
      cessation should be encouraged.

PMID- 15501351
TI  - [What have we learned about giant cell arteritis during the last decade?].
AB  - INTRODUCTION: We propose a review on the current state of knowledge in giant cell
      arteritis (GCA), with particular emphasis on advances produced during the past 10
      years. CURRENT KNOWLEDGE AND KEY POINTS: The physiopathology of GCA is better
      understood. GCA is considered as a T-cell mediated, antigen driven disease. The
      expression of interferon-gamma greatly influences the clinical expression of the
      vasculitis. The disease occurs preferentially in women. HLADR4 group and an
      atheromatous background have been shown to be risk factors for the disease.
      Infections (parainfluenzae virus, parvovirus B19) may act as triggers at the
      onset of GCA. In Europe, GCA incidence seems to be increasing in most countries
      in which it has been studied, especially in women. The diagnostic usefulness of
      the halo sign detected by high resolution Doppler ultrasonography seems limited.
      An excess of cardiovascular mortality is described in some countries. There is no
      consensus regarding the risk factors for thrombotic events. Randomized studies
      have not proved that methotrexate is a significantly efficient corticosteroid
      sparing agent. The value of high doses of methylprednisolone for severe
      thrombotic events has not been established. Benefits and risks of antiaggregation
      and anticoagulation are unknown. PERSPECTIVES: Numerous important questions
      regarding the management of GCA remain unresolved. Well designed prospective
      studies are rare, and necessary in the future.

PMID- 15501352
TI  - [Hemophagocytic syndrome complicating adult's seropositive rheumatoid arthritis].
AB  - INTRODUCTION: Macrophage activation syndrome (MAS) is a severe complication of
      chronic rheumatic diseases, particularly juvenile rheumatoid arthritis. However,
      MAS is rarely described in adult rheumatoid polyarthritis. EXEGESE: We report a
      case of MAS complicating a seropositive rheumatoid polyarthritis after 20 years
      of evolution. Pancytopenia with fever, renal failure and hepatic dysfunction
      revealed the disease that was confirmed by multiple macrophages and monocytes
      invading the bone marrow specimen. CONCLUSION: Outcome has been spectacular under
      corticosteroids.

PMID- 15501353
TI  - [Oculomotor muscles involvement revealing dermatomyositis in a patient with
      rheumatoid arthritis].
AB  - INTRODUCTION: Oculomotor muscles (OMM) involvement in dermatomyositis (DM) and in
      rheumatoid arthritis (RA) is unusual. The DM always leads to OMM inflammation,
      whereas the RA particularly leads to tenosynovitis of the superior oblique muscle
      referred to as the Brown syndrome. OBSERVATION: The patient is a 43-year-old
      woman who gives a 17-year-history of severe seropositive RA with bilateral
      coxite. She was hospitalized for acute painful proptosis. The clinical
      examination revealed an orbital erythema and a muscular rhizomelic weakness. The
      muscular enzymes were increased. The orbital CT revealed in the right side, an
      enlargement of the superior rectus muscle that was enhanced after intravenous
      injection, which is compatible with myositis involvement. The muscular biopsy
      practiced at the level of the calf showed the specific histological signs of the
      DM. This orbital involvement was resolved with a high dose of corticosteroids.
      CONCLUSION: Our observation has the specificity of associating RA with DM with an
      involvement of the superior rectus muscle, which is due to the DM rather than the
      RA.

PMID- 15501354
TI  - [Cardiac amyloidosis].

PMID- 15501355
TI  - [Lupus anticoagulant and Behcet's disease: increase of vascular risk?].

PMID- 15501356
TI  - [Aortic dissection in temporal arteritis].

PMID- 15501357
TI  - [Hypertrophic myopathy due to muscular metastasis of a signet cell adenocarcinoma
      of the bladder].

PMID- 15501358
TI  - [Unusual evolution of autoimmune hypothyroidism: occurrence of Grave's disease].

PMID- 15501360
TI  - Somnolence and other sleep disorders in Parkinson's disease: the challenge for
      the practicing neurologist.

PMID- 15501359
TI  - Neuroprotective agents in Parkinson's disease: clinical evidence and caveats.

PMID- 15501361
TI  - Autonomic dysfunction in Parkinson's disease.

PMID- 15501362
TI  - Parkinson's disease and quality of life: issues and challenges beyond motor
      symptoms.

PMID- 15501363
TI  - Future therapies for Parkinson's disease.

PMID- 15501364
TI  - Treatment challenges in early stage Parkinson's disease.

PMID- 15501365
TI  - Options in the treatment of motor fluctuations and dyskinesias in Parkinson's
      disease: a brief review.

PMID- 15501366
TI  - Freezing of gait in Parkinson's disease.

PMID- 15501367
TI  - Anxiety, depression, and psychosis in Parkinson's disease: unmet needs and
      treatment challenges.

PMID- 15501368
TI  - Cognitive issues in Parkinson's disease.

PMID- 15501370
TI  - Rethinking parenting interventions for drug-dependent mothers: from behavior
      management to fostering emotional bonds.
AB  - Mothers who are physically and/or psychologically dependent upon alcohol and
      illicit drugs are at risk for a wide range of parenting deficits beginning when
      their children are infants and continuing as their children move through school
      age and adolescent years. Behavioral parent training programs for drug-dependent
      mothers have had limited success in improving parent-child relationships or
      children's psychological adjustment. One reason behavioral parenting programs may
      have had limited success is the lack of attention to the emotional quality of the
      parent-child relationship. Research on attachment suggests that the emotional
      quality of mother-child relationships is an important predictor of children's
      psychological development through school-age and adolescent years. In this paper,
      we present a rationale and approach for developing attachment-based parenting
      interventions for drug-dependent mothers and report preliminary data on the
      feasibility of offering an attachment-based parenting intervention in an
      outpatient drug treatment program for women.

PMID- 15501371
TI  - Cost estimation when time and resources are limited: the Brief DATCAP.
AB  - The Drug Abuse Treatment Cost Analysis Program (DATCAP) was designed in the early
      1990s as a research guide to collect and analyze financial data from addiction
      treatment programs. The addiction research community could clearly benefit from a
      version of the DATCAP that reduced the time and effort required for its
      administration without compromising the integrity of its cost estimates. This
      paper introduces the Brief DATCAP and presents some preliminary findings. Initial
      feedback from respondents suggests that the Brief DATCAP is understandable, and
      easier and quicker to complete than the DATCAP. More importantly, preliminary
      results indicate that cost estimates from the Brief DATCAP differ from those of
      the longer DATCAP by less than 2%. These results have important research and
      policy implications because a shorter yet reasonably accurate cost instrument
      will enhance the feasibility and precision of future economic evaluations of
      addiction interventions.

PMID- 15501372
TI  - Services research on adolescent drug treatment. Commentary on "The Cannabis Youth
      Treatment (CYT) Study: main findings from two randomized trials".

PMID- 15501373
TI  - The Cannabis Youth Treatment (CYT) Study: main findings from two randomized
      trials.
AB  - This article presents the main outcome findings from two inter-related randomized
      trials conducted at four sites to evaluate the effectiveness and cost
      effectiveness of five short-term outpatient interventions for adolescents with
      cannabis use disorders. Trial 1 compared five sessions of Motivational
      Enhancement Therapy plus Cognitive Behavioral Therapy (MET/CBT) with a 12-session
      regimen of MET and CBT (MET/CBT12) and another that included family education and
      therapy components (Family Support Network [FSN]). Trial II compared the five
      session MET/CBT with the Adolescent Community Reinforcement Approach (ACRA) and
      Multidimensional Family Therapy (MDFT). The 600 cannabis users were predominately
      white males, aged 15-16. All five CYT interventions demonstrated significant pre
      post treatment during the 12 months after random assignment to a treatment
      intervention in the two main outcomes: days of abstinence and the percent of
      adolescents in recovery (no use or abuse/dependence problems and living in the
      community). Overall, the clinical outcomes were very similar across sites and
      conditions; however, after controlling for initial severity, the most cost
      effective interventions were MET/CBT5 and MET/CBT12 in Trial 1 and ACRA and
      MET/CBT5 in Trial 2. It is possible that the similar results occurred because
      outcomes were driven more by general factors beyond the treatment approaches
      tested in this study; or because of shared, general helping factors across
      therapies that help these teens attend to and decrease their connection to
      cannabis and alcohol.

PMID- 15501374
TI  - Parenting knowledge among substance abusing women in treatment.
AB  - The purpose of this study was to assess parenting knowledge and beliefs among
      drug abusing pregnant and recently postpartum women engaged in a comprehensive
      substance abuse treatment program. The effects of a parenting skills training
      program for this population were evaluated. A Parenting Skills Questionnaire was
      developed and administered to a sample of 73 pregnant and drug-dependent women
      during their first week of substance abuse treatment and again approximately 7
      weeks later, following parenting skills training. The questionnaire was designed
      to assess whether group and individual parenting sessions changed the subjects'
      knowledge and beliefs in four parenting domains: newborn care, feeding practices,
      child development and drug abuse during pregnancy. Pre-intervention scores for
      all parenting domains were low. Post- vs. pre-intervention comparisons showed
      significant increases in all domain scores after individual and group parenting
      skills training. Preliminary results obtained from this clinic-based sample
      suggest that these substance abusing mothers lacked important parenting knowledge
      and that this knowledge improved after comprehensive substance abuse treatment
      that included parenting training.

PMID- 15501375
TI  - Behavioral contingencies improve counseling attendance in an adaptive treatment
      model.
AB  - Poor patient adherence remains a serious obstacle to improving the effectiveness
      of many drug abuse therapies and the overall quality of care delivered in
      programs. The present study evaluated the utility and efficacy of incorporating
      behavioral contingencies in a stepped care treatment approach to motivate patient
      attendance to the varying amounts of prescribed weekly counseling. Study
      participants were opioid-dependent patients (n = 127) newly admitted to an
      ambulatory treatment program that provides methadone. Participants were randomly
      assigned to a Motivated Stepped Care condition (MSC; n = 65) with behavioral
      contingencies to specifically motivate counseling attendance vs. a Standard
      Stepped Care condition (SSC; n = 62) without these contingencies. The MSC vs. SSC
      condition was associated with a higher rate of counseling attendance (83% vs.
      44%, p < .001) and a lower rate of poor treatment response (46% vs. 79%, p <
      .001). The behavioral contingencies were well tolerated and strongly associated
      with excellent attendance across both lower and higher doses of weekly
      counseling.

PMID- 15501376
TI  - Linking female sex workers with substance abuse treatment.
AB  - We evaluated mobile street-based outreach as a modality for linking street
      walking female sex workers with substance abuse treatment in New York City. Sex
      workers (N = 179) approaching an existing outreach facility were randomly
      assigned to receive usually provided services, or to receive an enhanced version
      of these services. Among the 144 women successfully followed for 6 months, 35.0%
      were detoxified; 43.1% of the 78 current heroin users received methadone
      maintenance; and 35.4% of the followed-up clients received some other type of
      treatment. Intervention group differences in these outcomes were not significant.
      Detoxification during followup was associated with heroin dependence and lifetime
      detoxification. Methadone maintenance (among heroin users) was associated with
      Hispanic ethnicity and legally mandated treatment. Other types of treatments were
      negatively associated with the degree of involvement in the sex trade. We
      conclude that a variety of factors affect motivation for substance abuse
      treatment among female sex workers, and that street-based outreach is a highly
      effective modality for linking this population with much needed treatment.

PMID- 15501377
TI  - The Community Assessment Inventory--client views of supports to drug abuse
      treatment.
AB  - A measure assessing client views of the community supports available to them was
      developed and tested with entrants to outpatient drug free treatment. Items for a
      Community Assessment Inventory (CAI) fell into four areas of potential social
      support for treatment entry and engagement: (1) partner and/or family with whom
      living; (2) family living outside the home; (3) friends; and (4) the community
      itself. Based on 241 study participants, it was found that internal consistency
      alphas for the four scales ranged between .79 and .88. Both total CAI score and
      individual scales assessing support from friends and from partner/spouse were
      found capable of predicting treatment readiness as assessed using the TCU
      Motivation Scale. Evidence of construct validity was suggested by differences in
      CAI total score between participants reporting and not reporting involvement in
      discussions with others regarding crime and regarding drugs. Findings are also
      provided regarding leisure time activities and social relations of treatment
      entrants.

PMID- 15501378
TI  - Out of touch or on the money: Do the clinical objectives of addiction treatment
      coincide with economic evaluation results?
AB  - Previous economic studies have examined the association between substance abuse
      treatment and reduced costs to society, but it remains uncertain whether the
      economic measures used in cost and benefit-cost analyses of treatment programs
      correspond in direction and magnitude with clinical outcomes. In response to this
      uncertainty, the present study analyzed a longitudinal data set of addiction
      treatment clients to determine the statistical agreement between clinical and
      economic outcomes over time. Data were collected from 1,326 clients in the
      Chicago cohort of the Persistent Effects of Treatment Study. These individuals
      were interviewed at baseline as well as at 6-, 24-, 36-, and 48-month followup
      periods (91.6% followup). Correlations between clinical and economic measures
      were generally small (rho of 0.1 to 0.3) and often became non-significant once we
      controlled for baseline severity. The results demonstrate that although some
      associations exist, outcomes should be evaluated along both clinical and economic
      dimensions.

PMID- 15501379
TI  - Serum lead, cadmium, and zinc levels in newborns with neural tube defects from a
      polluted zone in Mexico.
AB  - Serum lead, cadmium and zinc levels from 31 newborns with neural tube defects
      (NTD), and 54 healthy controls living in a polluted area in Mexico were estimated
      using atomic absorption spectrophotometry (AAS). NTD family history was found to
      be of greater importance in the case group (OR 6.95, 95% CI 1.51-36.3, p=0.002).
      In 25% of the children, serum lead concentrations were above the admissible
      maximum level (AML) of 10 microg/dL within 24 h of extra-uterine life. Cadmium
      concentrations were below the AML. Zinc deficiency was found in nine (29%) of the
      cases and four (9.3%) of the controls (p=0.04). The logistic regression
      multivariate analysis showed no correlation between NTD and high levels of any of
      these metals; however, a positive correlation was found to zinc deficiency (OR
      5.0, 95% CI 1.07-23.00, p=0.04). These results focus attention to the surrounding
      nutritional and maternal health factors of major importance in disease etiology.

PMID- 15501380
TI  - In utero and lactational exposure of Long-Evans rats to ammonium perchlorate (AP)
      disrupts ovarian follicle maturation.
AB  - Ammonium perchlorate (AP) is a powerful oxidizer manufactured almost exclusively
      for the aerospace industry. AP salts are also used in airbags, flares,
      fertilizers, enamels and paints. As a result of widespread industrial use, AP has
      become a persistent environmental contaminant of drinking water in several U.S.
      states. AP ion disrupts the trapping of iodide as well as facilitates the
      discharge of unorganified iodide from the thyroid gland. Such disturbances in
      thyroid hormone concentrations during critical periods of development are then
      known to cause profound reproductive and developmental defects, since thyroid
      hormones modulate both follicular development and steroidogenesis and affect
      estrogen metabolism and receptor. This study was designed (1) to determine
      whether exposure to a low or high concentration of AP (LAP, HAP) exerts
      detrimental effects on follicle maturation in the Long-Evans hooded rat and (2)
      to determine whether the modulatory effects of AP can be ameliorated by levo
      thyroxine sodium (T4) supplementation. Animals were treated via deionized
      drinking water on GD 7-21 with LAP (0.4 mg/kg/day) or HAP (4.0 mg/kg/day). Half
      of each group was also given T4 supplements via drinking water on GD 7-21. Female
      pups were sacrificed on postnatal days 24/25, and the ovaries were excised, fixed
      for histology and analyzed. The analysis included a count, measurement and
      classification of preantral and antral follicles in the greatest cross-sectional
      area of the ovary. The results indicated that treatment with the HAP
      significantly reduced the number of preantral follicles <50,000 microm2 and the
      total number of antral follicles in the <50,000, 50-100,000 and >100,000 microm2
      size classes. In ovaries treated with the LAP, we observed no significant
      decrease in preantral follicles of any size class and only a significant
      reduction in the largest antral follicles. T4 only circumvented the effect on the
      number of small preantral and antral follicles; however, a significant diminution
      in the antral follicle number persisted in the mid-sized (HAP) and large (LAP,
      HAP)-sized classes. These data support the hypothesis that AP reduces the number
      of preantral and antral follicles in certain size classes in rats exposed during
      a critical period of development, and that T4 can attenuate the effects of AP on
      small preantral and antral follicles, but not on medium or large antral
      follicles. (T35ES007292 & ES08342.).

PMID- 15501381
TI  - Protective effect of DL-alpha-lipoic acid in cyclophosphamide induced oxidative
      injury in rat testis.
AB  - The aim of the present study was to evaluate the protective effect of DL-alpha
      lipoic acid on the biochemical changes, tissue peroxidative damage and abnormal
      antioxidant levels in the rat testis during cyclophosphamide (CP)-induced injury.
      Adult male Wistar rats were divided into four treatment groups: (I) control, (II)
      15 mg/kg CP once a week for 10 weeks by gavage, (III) 35 mg/kg lipoic acid once a
      week for 10 weeks by intraperitoneal injection, and (IV) CP plus lipoic acid (24
      h prior to CP administration). Testicular toxicity, assessed by decreased
      enzymatic activities of lactate dehydrogenase and glucose-6-phosphate
      dehydrogenase, was reversed with lipoic acid pretreatment. CP-exposed rats (group
      II) showed abnormal levels of enzymes (superoxide dismutase, catalase,
      glutathione peroxidase, glutathione-S-transferase and glutathione reductase) and
      antioxidants (reduced glutathione, ascorbate and alpha-tocopherol) along with
      high malondialdehyde levels. In contrast, rats pretreated with lipoic acid (group
      IV) showed normal lipid peroxidation and antioxidant defenses. These findings
      indicate a cytoprotective role of lipoic acid in this experimental model of
      testicular toxicity.

PMID- 15501382
TI  - Effects of PCB99 and PCB153 exposure on spermatogenesis in young adult C57BL6
      mice.
AB  - This study examined the effects of acute exposure to PCB99 (2,2',4,4',5
      pentachlorobiphenyl), and PCB153 (2,2',4,4'5,5'-hexachlorobiphenyl), on
      spermatogenesis in 8-week-old C57BL6 mice. The mice were randomly allocated to
      PCB99 and PCB153 and a single dose of respectively 10 and 100 mg/kg was given by
      oral gavage. During the 6-week experiment, six mice per treatment group were
      sacrificed weekly, body weights were recorded and samples with respect to the
      male reproductive system were collected until further analysis. None of the
      treatments, showed changes in body weight or reproductive endpoints. Flow
      cytometric analysis revealed spermatogenesis to be unaffected. However, PCB99 and
      PCB153 showed a significant increase in Leydig cell apoptosis. The results from
      the present study indicate that the male reproductive system is relatively
      refractory to PCB99 and PCB153 at levels exceeding those of wildlife and humans,
      when exposed during adult life. However, the finding of apoptotic Leydig cells
      merits further investigation.

PMID- 15501383
TI  - Effects of neonatal administration of 17beta-estradiol, beta-estradiol 3
      benzoate, or bisphenol A on mouse and rat spermatogenesis.
AB  - Bisphenol A (BPA) is a global environmental contaminant that has been implicated
      as a potential endocrine disruptor. In the present study, newborn rats and mice
      were injected subcutaneously with BPA to determine the potential developmental
      effects on the testis. Testes were examined by light and electron microscopy at
      15 weeks of age. Other groups of newborn mice and rats were injected with 17beta
      estradiol (E2) or beta-estradiol 3-benzoate (E2B) in a similar manner. BPA, E2,
      and E2B had similar effects on testes. When treated animals reached puberty and
      spermiogenesis began, the first sign of the effects was detected in the steps 2-3
      spermatids: the acrosomal granule and nucleus were deformed. Henceforth,
      abnormalities in the acrosome and nucleus were observed in older spermatids and
      spermatozoa. Ectoplasmic specialization between the Sertoli cell and spermatids
      was also affected: some specializations were partially or totally deleted. When
      animals fully matured, the effects of the agents were not found in the testes,
      and the animals were found to be fertile. The results of the present study show
      that BPA acts as an estrogen, and causes changes which appear to revert in
      adults.

PMID- 15501384
TI  - Influence of the mycotoxins alpha- and beta-zearalenol (ZOL) on regulators of cap
      dependent translation control in pig endometrial cells.
AB  - The molecular mechanisms that control the mycotoxin-mediated effects in porcine
      endometrial cells are far from being completely understood. Recent results show
      that they could inhibit cell proliferation. Therefore, the present study
      investigated the effects of the mycotoxins alpha-zearalenol (alpha-ZOL) and beta
      zearalenol (beta-ZOL) on a cellular level. Mainly, the abundance and
      phosphorylation state (activity) of the cell cycle-dependent kinases MAPK and Akt
      (PKB) and their potential targets eIF4E (eukaryotic initiation factor 4E) and 4E
      BP1 (4E binding protein, eIF4E repressor protein) were investigated. The results
      show that alpha-ZOL has apparently only a slight influence on the phosphorylation
      state of MAP kinases, Akt and on eIF4E and 4E-BP1. In contrast, their
      phosphorylation was strongly reduced in beta-ZOL-treated cells in a concentration
      dependent manner. Therefore, our results indicate that beta-ZOL potentially not
      only influences transcription but also effects gene expression on translational
      level. The effect of alpha- and beta-ZOL on endometrial cell proliferation and
      their toxicology are discussed.

PMID- 15501385
TI  - Effects of Vitamin C and E on PCB (Aroclor 1254) induced oxidative stress,
      androgen binding protein and lactate in rat Sertoli cells.
AB  - The effect of Aroclor 1254 and the ameliorative effect of Vitamin C and E on
      Sertoli cell function were studied in adult male rats. The rats were administered
      Aroclor 1254 at a dose of 2 mg/kg bw/day intraperitoneally for 30 days. One group
      of rats received Vitamin C (100 mg/kg bw/day) while the other group received
      Vitamin E (50 mg/kg bw/day) orally simultaneously with Aroclor 1254 for 30 days.
      Necropsy was performed at 24 h after the last injection. Sertoli cells were
      isolated for the estimation of enzymatic antioxidants superoxide dismutase (SOD),
      catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GST), and
      gamma-glutamyl transpeptidase (gamma-GT). Lipid peroxidation (LPO), hydrogen
      peroxide and hydroxyl radical were estimated. Sertoli cellular androgen binding
      protein (ABP) and lactate were also quantified. Whereas body weight, testis
      weight, relative weight of testis, ABP, lactate and specific activities of SOD,
      CAT, GPx, GR, GST, gamma-GT were all decreased, the levels of hydrogen peroxide,
      hydroxyl radical and LPO were significantly increased in the Sertoli cells of
      Aroclor 1254 treated rats. Simultaneous administration of Vitamin C or E restored
      these parameters to a normal range. Thus, the present study suggests that Aroclor
      1254 exposure induces oxidative stress in rat Sertoli cells and furthermore that
      simultaneous administration of Vitamin C or E ameliorated these effects.

PMID- 15501386
TI  - Correlation of chlorinated pesticides concentration in semen with seminal vesicle
      and prostatic markers.
AB  - Semen samples of fertile and infertile men were analysed by gas liquid
      chromatography (GLC) for the presence of dichlorodiphenyltrichloroethane (DDT)
      and its metabolites (1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene) (pp'-DDE);
      (1,1,1-trichloro-2,2-bis(p-chlorophenyl ethane) (pp'-DDT); (1,1-dichloro-2,2
      bis(p-chlorophenyl) ethane) (pp'-DDD); (1,1,1-trichloro-2-(o-chlorophenyl)-2-(p
      chlorophenyl) ethane) (op'-DDT), hexachlorocyclohexane (HCH) and its isomers
      alpha (alpha), beta (beta), gamma (gamma), delta (delta) and aldrin. The
      biochemical analysis of seminal vesicle and prostatic marker was done by
      spectrophotometer. The concentrations of alpha-, beta-, gamma-HCH, pp'-DDE and
      pp'-DDD were higher in the semen of infertile than in that of fertile men. An
      elevation in the fructose level along with decrease in the gamma-glutamyl
      transpeptidase and acid phosphatase activity was noticed in infertile men as
      compared to fertile subjects. The data showed correlation between alpha-, beta-,
      gamma-HCH, pp'-DDE, pp'-DDD and seminal vesicle marker fructose and prostatic
      marker gamma-gluatamyl transpeptidase and acid phosphatase in infertile men. The
      study suggests that the chlorinated pesticides may influence the semen quality by
      affecting the seminal and prostatic functions in infertile men.

PMID- 15501387
TI  - The toxic effects of nonylphenol on the reproductive system of male rats.
AB  - Male Sprague-Dawley (SD) rats were exposed to 4-t-nonylphenol (NP) by gavage at
      dosages of 0, 125 and 250 mg/kg/day for 50 days. Organ weights of liver, kidney,
      testis and epididymis were measured. Sperm number in the head of epididymis was
      counted. Several hormones including testosterone, luteinizing hormone and
      follicle stimulating hormone were measured. Testicular sections were observed by
      light and electron microscopy. Terminal dideoxynucleotidyl transferase dUTP nick
      end labeling assay was performed to probe the apoptotic cells in seminiferous
      tubules. When rats were treated with nonylphenol at 250 mg/kg/day, the absolute
      and relative weight of epididymis decreased dramatically, while the relative
      weights of kidney and liver increased by 14 and 22%, respectively. In addition,
      the sperm density of the head of epididymis and the testosterone level descended
      at 250 mg/kg/day. The levels of luteinizing hormone and follicle stimulating
      hormone increased in both nonylphenol treated groups. Pathological changes were
      detected by microscopy and the transferase dUTP nick end labeling (TUNEL) assay
      showed that the number of apoptotic cells in testes increased with nonylphenol in
      a dose-dependent manner.

PMID- 15501388
TI  - The effects of tetrathiomolybdate (TTM, NSC-714598) and copper supplementation on
      fertility and early embryonic development in rats.
AB  - Based on its ability to chelate copper, TTM is being studied as an antiangiogenic
      agent for cancer therapy. The purpose of this study was to evaluate the toxicity
      of TTM and the protection of copper supplementation on the reproductive
      capability of male and female CD rats. Doses of 0, 1, 4, and 12 mg/kg/day with
      copper supplementation (110 mg/kg of diet) were given by gavage. There were no
      effects on the estrous cycle or reproductive indices, or maternal toxicity in any
      female dose group. Male rats given 12 mg/kg/day showed significant decreases in
      body weight gains and food consumption, and anemia. Serum ceruloplasmin levels
      were dose-dependently decreased in all male dose groups. Reduced epididymal
      weights, sperm counts, and sperm motility, sperm morphologic abnormalities and
      histopathologic changes in testis and epididymis occurred only at 12 mg/kg/day.
      Dietary copper supplementation prevented the adverse sperm effects produced by 12
      mg/kg/day of TTM.

PMID- 15501389
TI  - Newer antidepressants in pregnancy: prospective outcome of a case series.
AB  - Antidepressant drug choice in pregnancy is a complex problem especially for new
      drugs. Among 590 cases exposed to drugs during pregnancy who were followed by our
      center, 21 cases used newer antidepressants, i.e., venlafaxine, mirtazapine,
      nefazodone. We present the gestational findings and fetal outcomes of these
      cases. Ten cases had used venlafaxine, one case had used both venlafaxine and
      mirtazapine, eight had used mirtazapine alone or with some other drugs and two
      had used nefazodone, in the first trimester. Of the 21 cases, 17 (80.9%) had
      healthy babies, 3 (14.3%) decided to terminate the pregnancy, and 1 (4.8%)
      spontaneous abortion was observed in a case exposed to mirtazapine, alprazolam,
      diazepam and trifluoperazine. All obstetrical findings were normal during the
      pregnancy of each case. No congenital abnormality and developmental problem was
      observed in the babies followed up for 12 months. The aim of the present study is
      to contribute the data to the limited knowledge available in the literature
      regarding human pregnancy.

PMID- 15501390
TI  - Induction of low dose oral tolerance in IL-10 deficient mice with experimental
      autoimmune encephalomyelitis.
AB  - IL-10 has been shown to be an important anti-inflammatory mediator that has both
      down-regulatory and immunomodulatory effects. Utilizing IL-10(-/-) mice we
      demonstrate the induction of low dose oral tolerance characterized by the up
      regulation of TGF-beta and IL-4 and the suppression of Ag specific proliferation
      with little suppression of INF-gamma. More severe EAE was found in IL-10(-/-)
      mice than in wild type controls, however, feeding resulted in amelioration of
      disease severity in both groups. Orally tolerized IL-10(-/-) mice had greater
      disease severity compared to orally tolerized wild type mice. IL-4 was present in
      the GALT of IL-10(-/-) mice and up-regulation of TGF-beta was detected in the
      lamina propria of fed mice. These results demonstrate that IL-10 is not required
      for the induction of low dose oral tolerance but is required for the regulation
      of INF-gamma which affects severity of disease in tolerized mice.

PMID- 15501391
TI  - Immunomodulation through inhibition of multiple adhesion molecules generates
      resistance to autoimmune diabetes in NOD mice.
AB  - The effect of simultaneous blockade of adhesion molecules on the development of
      long-term resistance to type 1 diabetes was investigated in an adoptive transfer
      model in NOD mice. Splenocytes isolated from acutely diabetic NOD mice injected
      into NOD-scid mice caused diabetes at 43 +/- 5.0 days. Treatment with anti-alpha4
      integrin monoclonal antibody (mAb) delayed the onset of insulitis and
      significantly delayed hyperglycemia to 66 +/- 5.8 days. Combination treatment
      with anti-alpha4-integrin and anti-LFA-1 mAbs delayed the onset of diabetes to
      >100 days (p<0.0001). Combination-treated mice were subjected to a second
      challenge with diabetogenic splenocytes after 85 days of normoglycemia. Without
      additional mAb treatment they developed hyperglycemia after significant delay (72
      +/- 8.1 days post-reinoculation). Splenocytes from combination-treated mice
      transferred protection from diabetes to naive NOD-scid mice when co-transferred
      with diabetogenic splenocytes. The long-surviving mice showed periislet
      infiltration with CD62L+ cells, which were not seen in the insulitis developing
      in control animals. These findings suggest that adhesion molecule blockade does
      not prevent homing and may affect effector cell action through activation of
      immunoregulatory suppressor cells, leading to protection against development of
      diabetes.

PMID- 15501392
TI  - Activation and attenuation of apoptosis of CD4+ T cells following in vivo
      exposure to two common environmental toxicants, trichloroacetaldehyde hydrate and
      trichloroacetic acid.
AB  - Exposure to occupationally relevant concentrations of the environmental
      pollutant, trichloroethylene (TCE), in the drinking water of autoimmune-prone
      MRL+/+ mice has been shown to promote the generation of lupus and autoimmune
      hepatitis in association with the activation of Interferon-gamma (IFN-gamma)
      producing CD4+ T cells. Since blocking TCE metabolism suppressed the TCE-induced
      alteration in immune function, the present study was initiated to determine
      whether the major metabolites of TCE, trichloroacetaldehyde hydrate (TCAH) and
      trichloroacetic acid (TCA) could also mediate these immunoregulatory affects in
      vivo. TCAH and TCA were administered to the drinking water of MRL+/+ mice for 4
      weeks. CD4+ T cells from TCAH and TCA-treated MRL+/+ mice, unlike CD4+ T cells
      from control mice, demonstrated functional and phenotypic signs of activation, as
      evidenced by increased IFN-gamma production in association with the increased
      percentage of CD62L(lo) CD4+ T cells. Interestingly, it was also found that the
      CD4+ T cells from the TCAH and TCA-treated mice showed a decreased susceptibility
      to the activation-induced cell death (AICD) form of apoptosis following re
      stimulation in vitro. By demonstrating that TCAH and TCA can activate CD4+ T
      cells and inhibit their apoptosis following in vivo exposure represents a
      mechanism by which environmental toxicants may induce or accelerate the
      development of autoimmune disease.

PMID- 15501393
TI  - Autoantigenicity of DFS70 is restricted to the conformational epitope of C
      terminal alpha-helical domain.
AB  - Autoantibodies against DFS70 (Dense Fine Speckles 70) are found in 30% of
      Japanese atopic dermatitis patients, and less frequently in patients with other
      diseases. We have recently reported that they are also seen in 11% of hospital
      workers, but in only approximately 2% of patients with systemic rheumatic
      disease. In this study, in order to investigate the possible pathological role of
      anti-DFS70 antibodies, fine epitope mapping was carried out using 93 anti-DFS70
      autoantibody-positive sera. Immunoblotting using overlapping peptides failed to
      reveal major linear epitopes. Western blotting using various truncated proteins
      showed a strikingly uniform epitope distribution on a suspected tertiary
      structure expressed by DFS70(349-435). Some sera showed reactivity only in an
      immunoprecipitation assay using an in vitro translated DFS70. Circular dichroism
      analysis revealed that DFS(349-435) contains an approximately 40% alpha-helical
      conformation, while an overlapping, non-antigenic peptide is composed of random
      coiled structures. The skewed single major epitope enabled us to establish a
      highly quantitative ELISA for the epitope region. Antibody titers showed no
      significant differences between the diseased group and healthy individuals. We
      propose that anti-DFS70 antibody may be a natural autoantibody, which might
      modify or reflect the inflammatory process of various disorders.

PMID- 15501394
TI  - 1alpha,25-dihydroxyvitamin D3 or analogue treated dendritic cells modulate human
      autoreactive T cells via the selective induction of apoptosis.
AB  - Epidemiological evidence indicates that the vitamin D status after birth
      modulates the risk for development of type 1 diabetes mellitus (T1DM). We
      previously demonstrated that the biologically active form of vitamin D, 1alpha,25
      dihydroxyvitamin D3 (1,25(OH)2D3), as well as its analogue TX527 permanently
      alter the morphology and T cell stimulatory function of human dendritic cells
      (DC). Here, we studied the mechanism of T cell modulation by 1,25(OH)2D3 or
      analogue treated DC. By using CFSE-labelled autoreactive T cells, we observed
      that T cell proliferation is hampered upon coculture with modulated DCs, i.e. T
      cells underwent fewer cycles of cell divisions when compared to T cells
      stimulated by nontreated DCs. Moreover, 1,25(OH)2D3 or analogue modulated DCs
      induced significantly higher numbers of early apoptotic (annexin V+/PI-) and/or
      late apoptotic (annexin V+/PI+) T cells. Apoptosis was selectively induced in T
      cells activated by modulated DC, since other T cells present in the same
      cultures, either resting or activated by control untreated DC, were unaffected.
      Thus, in vitro preconditioning of DC with 1,25(OH)2D3 or analogue yields
      regulatory DC that may interfere with ongoing autoimmunity in vivo without
      affecting T cells with other specificities.

PMID- 15501395
TI  - Apoptosis resistance in peripheral blood lymphocytes of alopecia areata patients.
AB  - Alopecia areata (AA) is a putative, cell-mediated autoimmune disease of anagen
      stage hair follicles. Inter- and intra-follicular lymphocytic infiltrates are
      associated with alopecia that may progress from an initially patchy presentation
      to extensive, even universal, hair loss. We previously noted in a mouse model of
      AA that regulatory T cells (Treg) are absent from draining lymph nodes and that
      expression of CD44v7 is transiently upregulated. Both features might explain
      autoreactive T cell persistence. Here we explored whether similar changes are
      seen in AA patients' peripheral blood mononuclear cells (PBMC). There was no
      clear evidence for a reduction in Treg as a possible means to support sustained T
      cell activation. However, progressive AA patients' PBMC displayed increased
      resistance towards apoptosis, which was accompanied by a decrease in CD95L+ and
      an increase in CD44v7+ cells. Notably, an expanded population of CD4+CD25+CD154+
      T cells in progressive AA patients' PBMC was apoptosis resistant and expressed
      CD44v7. Thus, survival of activated T cells in progressive AA patients' PBMC is
      apparently sustained by downregulation of CD95L and upregulation of CD44v7 which
      is known to be associated with anti-apoptotic gene expression.

PMID- 15501396
TI  - Autoantibodies to DFS70/LEDGF are increased in alopecia areata patients.
AB  - Alopecia areata (AA) has been suspected to be an autoimmune disease, although
      there is no distinct evidence, we investigated the relationship between AA and
      autoantibodies against dense fine speckles 70 kDa (DFS70) in 111 patients with
      alopecia and 105 healthy controls. The sera from 59 out of 111 (53%) Japanese
      alopecia patients were positive for anti-nuclear antibody (ANA), as compared to
      the sera of 16 out of 105 (15%) healthy controls (p < 0.001). Twenty percent
      (22/111) of the alopecia patients were shown to be positive for the prevalence of
      anti-DFS70 antibodies, as compared to 8% (8/105) of the healthy controls (p <
      0.01). IgG subclass analysis by ELISA showed that IgG1 and IgG2-anti-DFS70
      antibodies were dominant in alopecia patients. The DFS70 gene expression in the
      hair structures was clearly detected in both those with and those without the
      anti-DFS70 antibody by RT-PCR. Immunohistochemical techniques showed that the
      DFS70 was localized predominantly in the outer root sheath (ORS) cells. The
      elevated anti-DFS70 antibodies in alopecia patients and the localization of the
      DFS70 in the ORS suggest that autoantibodies against the DFS70 are related to the
      etiology in a certain population of AA.

PMID- 15501397
TI  - Abnormal expression of chemokine receptors in Behcet's disease: relationship to
      intracellular Th1/Th2 cytokines and to clinical manifestations.
AB  - Dynamic interplay between cytokines and chemokines directs trafficking of
      peripheral blood mononuclear cells to tissues in autoimmune and/or viral
      diseases. The aim of the current study was to define the expression on CD3+ T
      cells of six chemokine receptors associated with inflammatory sites and the
      expression of intracellular cytokines, such as interferon-gamma (IFN-gamma) and
      interleukin-4 (IL-4), in Behcet's disease (BD). Flow cytometry was used to detect
      chemokine receptor and intracytoplasmic cytokines' expression. We observed that
      CD3+ T cells in the peripheral blood express a restricted array of inflammatory
      chemokine receptors, specifically, CCR5, CCR6 and CXCR3, but little CCR1-3. The
      highest expression of CXCR3 on CD3+ T cells is associated with the presence of
      central nervous system (CNS) manifestations or pulmonary involvement. CXCR3 is
      the principal inflammatory chemokine receptor involved in BD. CCR5 chemokine
      receptor is increased in BD regardless of clinical manifestations. The frequency
      of IFN-gamma-producing cells expressing CXCR3+ CD3+ cells is significantly
      increased in patients with BD compared with normal controls. IL-4-producing cells
      are decreased in BD. These results demonstrate the predominance of type 1
      cytokine producing cells in CXCR3+ CD3+ T cells during BD. We hypothesize that
      CXCR3 is the principal inflammatory chemokine receptor involved in BD,
      particularly during CNS and pulmonary manifestations.

PMID- 15501398
TI  - Expression of beta-cell autoimmunity does not differ between potential dizygotic
      twins and siblings of patients with type 1 diabetes.
AB  - Twin studies help to elucidate the contribution of genes and environment to type
      1 diabetes (T1DM). The Diabetes Prevention Trial-1 (DPT-1) tested for anti-islet
      autoantibodies: 34,765 non-diabetic non-twin siblings of patients with T1DM, and
      896 non-diabetic potential twins of patients with T1DM. Zygosity (being
      monozygotic [MZ] or dizygotic [DZ]) was unknown except for 357 non-diabetic
      subjects with opposite gender to their diabetic twin, who must be DZ. Expression
      of cytoplasmic islet cell (ICA), GAD65, ICA512 and insulin autoantibodies in 357
      different-sex (DZ) potential non-diabetic twins of T1DM patients was,
      respectively, 4.5%, 4.7%, 3.0% and 2.4%, which was lower than in 539 same-sex
      potential non-diabetic twins (including MZ and DZ) of T1DM patients for ICA
      (7.8%, p < 0.05), GAD65 (13.4%, p < 0.0001) and ICA512 (6.5%, p < 0.03). In
      contrast, expression of ICA, GAD65, ICA512 and insulin autoantibodies was not
      significantly different in different-sex (DZ) potential twins versus all siblings
      (respectively, 4.2%, 4.8%, 2.2%, 2.5%), different-sex siblings (3.9%, 4.9%, 2.2%,
      2.5%) or same-sex siblings (4.4%, 4.7%, 2.2%, 2.5%) of T1DM patients. In
      conclusion, anti-islet autoimmunity is not increased in non-diabetic DZ twins of
      T1DM patients compared to non-diabetic siblings of T1DM patients, suggesting that
      the greater environmental sharing by twins does not increase risk of anti-islet
      autoimmunity.

PMID- 15501399
TI  - Molecular characterization of the OspA(161-175) T cell epitope associated with
      treatment-resistant Lyme arthritis: differences among the three pathogenic
      species of Borrelia burgdorferi sensu lato.
AB  - Treatment-resistant Lyme arthritis, which may result from infection-induced
      autoimmunity, is associated with reactivity to a T cell epitope of outer-surface
      protein A (OspA(161-175)) of Borrelia burgdorferi sensu stricto (Bb). This
      syndrome has been noted primarily in the United States where only Bb is present,
      and rarely in Europe where Borrelia garinii (Bg) and Borrelia afzelii (Ba)
      predominate. To gain a better understanding of this epitope, we identified its
      species-specific polymorphisms, determined their immunogenicity, and
      characterized the contribution of individual amino acids. Based on published
      sequences the Bb peptide differed from the Ba peptide in six of the nine core
      residues (amino acids 165-173), whereas the Bg peptide usually differed in three
      of the nine residues. Lymphocytes from seven patients with treatment-resistant
      Lyme arthritis proliferated in response to the Bb peptide, but not to the Ba or
      Bg peptide. Substitution analysis showed that valine166 and threonine172 were
      critical for the immunogenicity of the Bb peptide. Thus, consistent with the
      geographic distribution of the illness, the European causative agents of Lyme
      borreliosis usually lack the putative pathogenic OspA epitope. These observations
      are consistent with the hypothesis that T cell recognition of this epitope is
      important in the induction of autoimmunity in treatment-resistant Lyme arthritis.

PMID- 15501400
TI  - Perlecan in late stages of osteoarthritis of the human knee joint.
AB  - OBJECTIVE: Disturbances of the proteoglycan metabolism play an essential role in
      the pathology of osteoarthritis. The extracellular matrix proteoglycan, perlecan,
      has lately been identified as a cell biological factor in cartilage development
      and maintenance. We investigated the tissue distribution of perlecan, the
      relation between the level of the protein and its mRNA and which type of cell,
      type 1 chondrocytes or elongated secretory type 2 cells, produces perlecan in
      late stages of osteoarthritis. METHODS: In 10 patients suffering from late-stage
      osteoarthritis tissue samples taken from a macroscopically intact area and the
      area adjacent to the main cartilage defect were investigated. We performed
      quantitative immunogold histochemistry and in situ hybridization in vivo and
      determined the level of perlecan mRNA with the help of real-time RT-PCR in native
      cartilage tissue and in cultured cells. RESULTS: In vivo, an increased level of
      perlecan protein was found in the area adjacent to the main defect. A 45% rise in
      the level of perlecan mRNA secreted by elongated secretory type 2 cells in
      comparison to type 1 chondrocytes was detected. Type 2 cells also translated the
      highest levels of perlecan to be deposited mainly in the pericellular matrix, and
      also in the interterritorial matrix in late stages of osteoarthritis. Also in
      vitro, type 2 cells showed a 50% higher level of mRNA for perlecan. CONCLUSION:
      We found evidence that perlecan is involved in the pathogenesis of late stages of
      osteoarthritis. The levels of perlecan protein and mRNA are up-regulated
      especially by the elongated secretory type 2 cells in the area adjacent to the
      main cartilage defect. This might be seen as an attempt on the part of the
      cartilage tissue to stabilize the extracellular matrix.

PMID- 15501401
TI  - Nitric oxide decreases IGF-1 receptor function in vitro; glutathione depletion
      enhances this effect in vivo.
AB  - Insulin-like growth factor-1 (IGF) helps maintain healthy articular cartilage;
      however, arthritic cartilage becomes less responsive to the anabolic actions of
      IGF. We previously showed that high concentrations of nitric oxide (NO) decrease
      IGF receptor tyrosine phosphorylation and response to IGF in intact chondrocytes.
      The current studies evaluate direct effects of NO on IGF receptor kinase (IGF-RK)
      in vitro. NO from S-nitroso-N-acetyl-d,l-penicillamine (SNAP) or 1-hydroxy-2-oxo
      3-(N-3-methyl-aminopropyl)-3-methyl-1-triazene (NOC-7) inhibits IGF-RK auto- and
      substrate phosphorylation in a dose and time dependent manner. There is a linear
      correlation between inhibition of auto- and substrate phosphorylation
      (r(2)=0.98). Increasing either dithiothreitol or reduced glutathione (GSH)
      content of the phosphorylation buffer to protect thiol groups blocks NO
      inhibition of IGF-RK substrate phosphorylation. Increased S-nitrosylation of
      cysteines in IGF-RK after exposure to SNAP suggests that NO may react with
      sulfhydryl groups, form S-nitrosothiols, which may result in functional
      modifications. NO blockade of IGF-1 stimulated proteoglycan synthesis in intact
      cells is enhanced when chondrocyte glutathione is depleted. The in vitro system
      shows that there can be direct effects of NO on IGF-RK that modify receptor
      function; the intact cell studies suggest that the mechanisms identified in vitro
      may be important in intact chondrocyte insensitivity to IGF-1 in cells exposed to
      NO.

PMID- 15501402
TI  - Testican-1, an inhibitor of pro-MMP-2 activation, is expressed in cartilage.
AB  - OBJECTIVE: Recently, testican-1 has been described to be an inhibitor of MT1-MMP
      and MT3-MMP mediated pro-MMP-2 activation. As MT1-MMP mediated pro-MMP-2
      activation is of significance for cartilage destruction in osteoarthritis, we
      studied the expression and localization of testican-1 in human articular
      cartilage. METHODS: Cartilage samples from the medial and lateral tibia plateau
      were obtained from osteoarthritic patients who underwent joint replacements, and
      were graded histomorphologically by Mankin score. Testican-1 expression was
      assessed in RNA isolated directly from cartilage as well as in freshly isolated
      chondrocytes by reverse transcriptase-polymerase chain reaction (RT-PCR) and
      quantified by real-time RT-PCR. Testican-1 protein was localized by
      immunohistochemistry in human osteoarthritic cartilage samples, in human fetal
      knee joint, and in knees from mice. RESULTS: Testican-1 mRNA could be detected in
      cartilage and in freshly isolated chondrocytes both from moderately and from
      severely damaged osteoarthritic cartilage. In the same donor, expression in
      chondrocytes from more severely affected regions was decreased compared with
      chondrocytes from less affected regions. By immunolocalization, testican-1
      protein could be detected in chondrocytes predominantly of the superficial and
      transitional zones. Matrix staining in these zones was greatly reduced in samples
      from more severely affected osteoarthritic cartilage. A similar distribution was
      found in the articular cartilage of knees from 7-week-old mice. In addition to
      articular cartilage, testican-1 was also present in growth plate cartilage.
      CONCLUSIONS: Testican-1 is a component of cartilage, both of the joint and of the
      growth plate. Given its activity as an inhibitor of MT1-MMP mediated pro-MMP-2
      activation, it is reasonable to speculate that it participates in the regulation
      of matrix turnover in cartilage.

PMID- 15501403
TI  - Histopathological correlation of cartilage swelling detected by magnetic
      resonance imaging in early experimental osteoarthritis.
AB  - OBJECTIVE: We previously reported that an increase of cartilage thickness is the
      earliest measurable change by magnetic resonance imaging (MRI) in early stages of
      experimental osteoarthritis (OA). Our present objective was to study the
      microscopic translation of this finding in order to know whether the cartilage
      thickness increment represents the earliest structural damage or whether it
      alternatively constitutes a non-progressive reversible phenomenon. METHODS: OA
      was induced by partial medial meniscectomy in rabbits. Normal and sham-operated
      animals were used as controls. Gross and microscopic cartilage changes were
      sequentially assessed after surgery at 0, 2, 4, 6, 8, 10 and 52 weeks, and
      compared to MRI findings. RESULTS: The swelling of cartilage detected by MRI
      correlated with depletion in matrix proteoglycans and cellular loss, which were
      closely related to the progression of OA at the earliest stages. Abnormalities of
      the cartilage structure appeared only in advanced OA. CONCLUSION: Cartilage
      swelling detected by MRI is due to proteoglycan depletion and represents the
      earliest abnormality in OA. Because it is accompanied by cellular loss, it cannot
      be merely attributed to surgical trauma and represents true tissue damage. The
      biological meaning of volume variations detected by MRI should be assessed
      carefully taking into account the disease stage as an increase in cartilage
      height also reflects cartilage damage and not a reparative process.

PMID- 15501404
TI  - The structural adaptations in compressed articular cartilage by microscopic MRI
      (microMRI) T(2) anisotropy.
AB  - OBJECTIVES: To detect structural adaptations of collagen fiber matrix in
      compressed articular cartilage in individual sub-tissue zones by microscopic
      magnetic resonance imaging (microMRI) at 23 microm in-depth resolution. DESIGN:
      Each of the six beagle humeral cartilage specimens was placed in a specially
      built nonmetallic compression device inside an in-situ rotation device, and was
      imaged four times at 7T: without and during static compression, and at two
      orientations: 0 degrees and 55 degrees . Proton intensity images and quantitative
      T(2) maps were constructed and analyzed. RESULTS: Upon compression at 55 degrees
      (the magic angle), rather than appearing homogenous, T(2)-weighted intensity
      images of cartilage showed a distinct laminar appearance and the T(2) profiles
      exhibited two distinctive peaks. At both 0 degrees and 55 degrees orientations,
      lower values of T(2) were observed in compressed tissue. A significant
      correlation was established between changes in tissue T(2) at 55 degrees and a
      thickness reduction due to compression. At a mean of 20% strain value,
      modifications in cartilage structure were studied at each histological zone. We
      found that the percentage of superficial zone was significantly doubled, the
      percentage of radial zone was significantly decreased by 10%, and no significant
      change in the transitional zone. CONCLUSIONS: External loading can induce a new
      kind of laminar appearance at the magic angle. microMRI T(2) anisotropy can be
      used to analyze the zone-specific alterations in collagen fibril organization in
      articular cartilage in response to mechanical compression.

PMID- 15501405
TI  - Implication of prostaglandin E(2) in TNF-alpha-induced release of m-calpain from
      HCS-2/8 chondrocytes. Inhibition of m-calpain release by NSAIDs.
AB  - OBJECTIVE: Calpains are known as Ca(2+)-dependent intracellular neutral cysteine
      proteases. However, m-calpain is detected in synovial fluid of arthritic joints
      and is shown to possess the proteoglycanase activity in vitro. The mechanism of m
      calpain release into the extracellular spaces during arthritis has not yet been
      well characterized. In the present study, we have analyzed m-calpain release from
      cultured chondrocytes stimulated by a proinflammatory cytokine, tumor necrosis
      factor-alpha (TNF-alpha). The effects of non-steroidal anti-inflammatory drugs
      (NSAIDs) on m-calpain release were also examined. METHODS: Human chondrocytic HCS
      2/8 cells were stimulated by TNF-alpha in the presence or absence of an NSAID. m
      Calpain in the cells and culture medium was quantified by Western blot analysis
      using an anti-m-calpain antibody. Western blots were subjected to densitometric
      analysis and band intensities were determined. RESULTS: TNF-alpha (10 ng/ml)
      stimulated m-calpain release with transient increase in cellular m-calpain in HCS
      2/8 cells. NSAIDs examined (aspirin, loxoprofen-SRS, diclofenac sodium,
      indomethacin and NS398) inhibited m-calpain release and production of
      prostaglandin E(2) (PGE(2)) induced by 10 ng/ml TNF-alpha. Exogenously added
      PGE(2) accelerated the release of m-calpain in response to a lower concentration
      of TNF-alpha (1 ng/ml). AH6809, an EP1/2 antagonist, but not SC19220 (an EP1
      antagonist), effectively inhibited TNF-alpha-induced m-calpain release. In
      contrast, butaprost, an EP2 agonist, accelerated release of m-calpain by 1 ng/ml
      TNF-alpha. CONCLUSIONS: These results suggest that TNF-alpha stimulates
      upregulation and release of m-calpain in chondrocytic HCS-2/8 cells, and that
      stimulation of EP2-PGE(2) receptor by produced PGE(2) is deeply involved in this
      process.

PMID- 15501406
TI  - Treatment with calcitonin prevents the net loss of collagen, hyaluronan and
      proteoglycan aggregates from cartilage in the early stages of canine experimental
      osteoarthritis.
AB  - OBJECTIVE: To evaluate the effect of calcitonin (CT) on the histology and
      biochemistry of articular cartilage from unstable operated and nonoperated knee
      in a canine model of experimental osteoarthritis (OA). METHODS: Eighteen dogs
      underwent anterior cruciate ligament transection (ACLT) of the right knee and
      were randomly distributed into three groups of six dogs each. From day-1 after
      surgery until sacrifice 84 days post-ACLT, each dog received a daily nasal spray
      that delivered the placebo, 100 units of CT or 400 units of CT. Histologic
      lesions were scored. Hyaluronan (HA) and antigenic keratan sulfate (AgKS) were
      quantified by enzyme-linked immunosorbent assays (ELISAs), whereas aggrecan
      molecules extracted under nondissociative conditions were characterized by
      velocity gradient centrifugation. RESULTS: All canine cruciate-deficient knees
      developed OA. At a daily dose of 400 units, CT had no effect on the size of
      osteophytes but significantly reduced the severity of cartilage histologic
      lesions in unstable knees. CT also enhanced the HA content as well as the size
      distribution and relative abundance of fast-sedimenting aggrecan aggregates in
      cartilage from both operated and nonoperated knees. On the other hand, in the CT
      treated group, the cartilage content of AgKS increased in operated joints, but
      not in nonoperated joints. CONCLUSIONS: Because CT delivered as a nasal spray
      markedly reduced the severity of most OA changes, both at the histological and
      biochemical level, this form of therapy may have benefits for humans who have
      recently experienced a traumatic knee injury, and as well as for dogs who
      spontaneously rupture their ACL.

PMID- 15501407
TI  - Responsiveness of the electronic touch screen WOMAC 3.1 OA Index in a short term
      clinical trial with rofecoxib.
AB  - BACKGROUND: The Western Ontario and McMaster Universities (WOMAC) Osteoarthritis
      Index is a self-administered validated questionnaire for patients with
      osteoarthritis (OA) of the hip or knee. The electronic touch screen version of
      the WOMAC (e-WOMAC) has been previously shown to be highly correlated with the
      original paper format. However, whether the e-WOMAC would be suitable for
      monitoring the effects of drug treatment is unknown. AIM: To validate the
      longitudinal use of the e-WOMAC questionnaire and its ability to detect changes
      in WOMAC-scores induced by drug treatment in outpatient care. METHODS: Fifty
      three outpatients, men and women (mean age: 64 years; SD+/-9.5), with symptomatic
      osteoarthritis of hip or knee were included in an open label study with
      rofecoxib. At three visits over 3 weeks, responsiveness of the WOMAC 3.1
      regarding the three subscales, pain, stiffness and function, were compared for
      the original paper format and the computer touch screen format (QUALITOUCH) using
      a Likert scale. WOMAC scores were transformed to the 0-100 scale. ANOVA for
      repeated measures was used for analysis and effect sizes by subscale were
      compared for both formats. RESULTS: Responsiveness for all three subscales was
      similar between formats. In both formats, pain and stiffness were significantly
      reduced with rofecoxib as early as 7 days, while functional ability was
      significantly increased (P<0.01 for all aggregate subscale scores) with
      continuing improvement until the end of study. The effect sizes by subscale
      between Day 1 and 21 were not statistically different between the paper and the
      electronic version of the questionnaire and showed similar clinically meaningful
      improvements in WOMAC scores over 3 weeks. CONCLUSION: In this longitudinal
      intervention study, the e-WOMAC OA Index 3.1 showed similar responsiveness in
      detecting clinically meaningful changes than the original paper format.

PMID- 15501408
TI  - Characterization of mature vs aged rabbit articular cartilage: analysis of cell
      density, apoptosis-related gene expression and mechanisms controlling chondrocyte
      apoptosis.
AB  - OBJECTIVE: The prevalence of osteoarthritis (OA) is increased in aged individuals
      and a direct correlation between chondrocyte apoptosis and cartilage degradation
      secondary to OA has been demonstrated. To address the question of whether age
      predisposes articular cartilage to apoptosis, the objective of the present study
      was to characterize and compare in aged and mature non-OA rabbit articular
      cartilage, cell density and expression levels of specific genes associated with
      apoptosis. Mechanistic studies on the inhibition of induced apoptosis were also
      carried out. METHODS: Grade I (non-OA) femoral condyles and tibial plateaus from
      mature and aged rabbits were taken for assessment of viable cell density (VCD)
      and mRNA (reverse transcription-polymerase chain reaction) expression levels of
      the pro-apoptotic genes, Fas, Fas ligand (FasL), caspase-8, inducible nitric
      oxide synthase (iNOS) and p53. In vitro insulin-like growth factor (IGF-1)
      mediated inhibition of nitric oxide (NO)-induced apoptosis was also examined
      using sodium nitroprusside (SNP) as NO donor. RESULTS: VCD was decreased 50-70%
      in aged articular cartilage relative to mature cartilage. mRNA expression levels
      of Fas, FasL, caspase-8 and p53 were higher in aged cartilage than in mature
      cartilage. iNOS expression was unchanged. IGF-1-mediated inhibition of NO-induced
      apoptosis was dose-dependent and reversed with addition of phosphatidylinositol-3
      kinase inhibitor. CONCLUSIONS: This controlled animal model study demonstrates
      that age predisposes articular cartilage to changes in VCD and expression levels
      of specific pro-apoptotic genes. It is significant that these findings were
      demonstrated on cartilage that showed no prior signs of OA; it is also possible
      that such changes are a prelude to the age-related development of OA.

PMID- 15501409
TI  - Molecular phenotyping of HCS-2/8 cells as an in vitro model of human
      chondrocytes.
AB  - OBJECTIVE: Cultures of primary articular chondrocytes for studying chondrocyte
      biology are notoriously difficult to handle. One alternative is the use of
      chondrocytic cell lines. Because the HCS-2/8 cells are the most widely used cell
      line in cartilage research, we investigated the molecular phenotype of these
      cells by mRNA-expression profiling. DESIGN: Monolayers of HCS-2/8 cells were
      cultured to sub-confluence, confluence and over-confluence; primary human
      chondrocytes were grown in monolayer culture and alginate-bead cultures and
      several other chondrocytic cell lines were cultured as monolayers. RNA was
      isolated and analyzed by cDNA array profiling using Affymetrix GeneChips
      (U95A/U95Av2) and quantitative PCR. RESULTS: Important similarities, but also
      remarkable differences between the HCS-2/8 cells and adult human articular
      chondrocytes were detected: Aggrecan and several cartilage typical collagens as
      well as SOX9 transcripts were strongly expressed in HCS-2/8 cells, whereas HCS
      2/8 cells expressed hardly any chondrocyte-typical cartilage matrix degrading
      enzymes. Of all culturing conditions, clustering analysis showed that HCS-2/8
      cultured at confluence are most closely related to primary chondrocytes.
      CONCLUSION: Our study confirms how careful one needs to be in choosing in vitro
      model systems for investigating effects of interest. The major issue of
      chondrocyte cell lines appears to be that they mainly proliferate and show less
      expression of genes of matrix synthesis and turnover. A successful approach will
      have to select suitable chondrocyte cell lines and to validate findings obtained
      using primary chondrocytes. This allows to establish a reproducible in vitro
      model showing the property of interest and subsequently to relate back the
      obtained results to the physiologic situation.

PMID- 15501411
TI  - Practical aspects of direct adsorption of lipoproteins from whole blood by DALI
      LDL-apheresis.
AB  - Direct adsorption of lipoproteins (DALI) from whole blood is the first LDL
      hemoperfusion procedure. The present paper addresses practical questions of DALI
      apheresis in order to optimise DALI therapy in sometimes critically ill coronary
      patients. The reduction of LDL and Lp(a) by DALI can be optimised by increasing
      the treated blood volume and the DALI adsorber volume. Hypotension (1.2% of
      sessions) may be minimised by fluid intake before the session, isovolemic
      connection of the patient to the ECC, reduced blood flow and low ACD-A ratio.
      Hypocalcemia may be avoided by low citrate anticoagulation (1:40) and reduced
      blood flow. Bradykinin release peaks at ca. 1000 ml of treated blood volume and
      may cause Quincke edema (tight throat), hypotension and flush. Reduction of the
      blood flow rate and decrease of citrate admixture as well as administration of
      iv. calcium may be helpful. While ACE inhibitors are contraindicated in DALI
      patients, sartans may be used without problems. Some "intrinsic" PTT increase is
      caused by adsorption of coagulation factors; undue PTT prolongations after DALI
      may be avoided by reduction of the heparin dosage during priming and treatment.
      In patients prone to alkalosis and hypokalemia, a reduction of the ACD-A ratio is
      recommended. Rises of adsorber inlet pressure may be due to insufficient
      anticoagulation and adsorber clotting or malfunctioning of the venous access.
      Rinsing of the adsorber with saline, administration of a heparin bolus and
      increase of the citrate admixture as well as a rinse and/or repositioning of the
      venous access are helpful measures. If these basic rules are followed, DALI LDL
      apheresis is a safe, efficient, rapid and user-friendly LDL-apheresis procedure
      as evidenced by more than 80,000 DALI sessions successfully performed to date.

PMID- 15501412
TI  - Effects of replacement fluids used for therapeutic plasma exchange on plasma
      viscosity and plasma oncotic pressure.
AB  - INTRODUCTION: Apheresis is a procedure in which one of the components of blood is
      removed. The aim of therapeutic plasma exchange (TPE) is to remove a large
      fraction of the patient's plasma from the body, and to exchange this with
      replacement solutions using automatic devices. With this procedure circulating
      pathogens and toxins are reduced. Before each TPE results of a baseline basal
      complete blood count, serum protein electrophoresis, coagulation tests and serum
      electrolytes must be known. The efficacy of this therapy is assessed only by
      these values. The proteins responsible for disease may be monoclonal proteins,
      cryoglobulins, lipoproteins, auto or allo antibodies or toxins. In this study, we
      aimed to compare the effects of several replacement fluids on plasma viscosity
      and oncotic pressure. At the same time, we evaluated the correlation between
      plasma viscosity and oncotic pressure. MATERIAL AND METHODS: 111 TPE were
      performed on 42 patients. Before TPE, the patients whose veins were not suitable
      were catheterised either by using a subclavian or jugular 11F dialysis catheter.
      At each session, approximately 1-1.5L of plasma was exchanged. The procedure was
      performed with albumin in patients whose albumin was under 3gr/dl. Over this
      value, the exchange fluids were randomised. RESULTS: When the overall results
      were analysed, there was no statistically significant difference between groups 1
      (HES+albumin) and group 3 (albumin). The statistical difference between group 2
      and 3 was significant, but no difference was observed between group 1 and 2.
      According to the decreasing plasma viscosity, there was a significant difference
      between group 2 and group 3, but there was no difference between group 1 and
      group 2. CONCLUSIONS: The replacement solutions used for plasmapheresis are
      similar when compared for hemorheologic effects, but we have chosen fresh frozen
      plasma because of fewer side effects.

PMID- 15501413
TI  - Hemovigilance for improvement of blood safety.

PMID- 15501414
TI  - Worldwide overview of existing haemovigilance systems.
AB  - Haemovigilance is a "quality process" with the aim to improve quality and
      increase safety of blood transfusion, taking into account that haemovigilance
      covers and surveys all activities of the blood transfusion chain from donors to
      recipients. Haemovigilance is indispensable when it comes to safety and quality
      of blood transfusions. Within the European Union (EU), the European Blood
      Directive requires haemovigilance in each Member State: the intention has been to
      rely on the existing or developing national systems. There are significant
      differences in haemovigilance around the world, in terms of definition,
      organisational schemes, state of development and implementation. These
      differences are more pronounced outside the EU: in some countries, even basic
      traceability causes a problem while in others systems similar as the most
      developed ones in the EU are implemented.

PMID- 15501415
TI  - The Quebec hemovigilance system: description and results from the first two
      years.
AB  - Following federal and provincial reviews of the blood system, the Canadian
      province of Quebec passed a series of legislative and administrative measures to
      improve blood safety, including the establishment of a hemovigilance system, and
      made infrastructure and human resource investments to support their
      implementation. The Quebec hemovigilance system was inspired by the French system
      using similar data elements and case definitions, grading of severity and
      determination of likelihood of association with transfusion for adverse
      transfusion events (ATE). The Quebec system also monitors transfusion incidents
      without adverse consequences such as "incorrect blood component transfused"
      (IBCT) and near-miss events. Accurate rate estimates are possible through the
      collection of denominator data on the number of blood products transfused. This
      paper describes the Quebec hemovigilance system and reports on ATE (including
      IBCT but excluding near-miss events) associated with blood components notified in
      2000 and 2001, the first two years of implementation. The Quebec hemovigilance
      system is voluntary, but hospital participation in 2000 and 2001 represented 80%
      and 82% of transfused products, respectively. Notified ATE (including IBCT)
      increased 78% between 2000 and 2001 primarily because of better reporting of
      minor adverse reactions. In 2001, the overall ATE rate was 3.5 per 1000 blood
      components transfused. Despite an overall increase in reported ATE, rates for
      some serious ATE decreased in the second year, including ABO-incompatible
      transfusions, acute hemolytic reactions and bacterial contamination.

PMID- 15501416
TI  - 6 Years of shot reporting--its influence on UK blood safety.
AB  - Recognition of the importance of systematic surveillance of adverse effects of
      transfusion has led to the development of haemovigilance schemes [Faber JC.
      Haemovigilance around the world. Vox Sang 2002;83(suppl.1):71], of which the
      Serious Hazards of Transfusion (SHOT) scheme, launched in 1996, was one of the
      first. Over 90% of UK hospitals now participate in the scheme; in 6 years of
      reporting, SHOT analysed 1630 events of which 64% were errors in the transfusion
      process, leading to 193 instances of ABO incompatible transfusion. Transfusion
      related acute lung injury, bacterial contamination of platelets and transfusion
      associated graft-versus-host disease were also identified as important
      preventable causes of mortality and morbidity. Data from SHOT has provided
      evidence to support the development of blood safety strategies in the UK.

PMID- 15501418
TI  - The French Haemovigilance System: organization and results for 2003.
AB  - In 1993 by law, in France, haemovigilance became a national system of
      surveillance and alert, from blood collection to the follow-up of the recipients,
      gathering and analysing all adverse events of blood transfusion in order to
      prevent their recurrences. In 2003, 2911 incidents with strong imputability have
      been specially analysed, among them seven confirmed cases of bacterial
      contamination, 137 incorrect blood components transfused with 12 cases of ABO
      incompatibility, 15 adverse reactions diagnosed as TRALI and 12 deaths. The
      analysis of information provided by haemovigilance has led to the implementation
      of new guidelines.

PMID- 15501417
TI  - Experience with the medical event reporting system for transfusion medicine (MERS
      TM) at three hospitals.
AB  - BACKGROUND: The MERS-TM assists hospital transfusion services to identify,
      analyze, and correct system events relating to the delivery of blood to patients.
      METHODS: The MERS-TM system was used from February of 1999 to December 2002. All
      reported near-miss and actual events were recorded and analyzed. RESULTS: During
      these 47 months, 4670 events were reported by the transfusion service. Of these
      events, 94% were classified as a near-miss event and 93% were detected before the
      blood product was administered. No ABO-incompatible transfusions were detected
      despite transfusion of 50,137 units of red blood cells. High severity events with
      the potential for patient harm accounted for 241 (5%) of the 4670 events. Nursing
      related events accounted for 188 (78%) of the high severity events. In one out of
      4430 (0.023%) samples tested, a high severity sample-testing event was detected.
      In one out of 1550 (0.06%) samples collected, a high severity sample-collection
      event was detected. CONCLUSION: An event reporting system is essential if one is
      to determine where and how often events are occurring within the transfusion
      process.

PMID- 15501419
TI  - Bacterial contamination in blood components and preventative strategies: an
      overview.
AB  - Bacterial contamination of blood and its cellular components remains an
      unresolved problem in transfusion medicine and is considered to be the most
      common microbiological cause of transfusion associated morbidity and mortality.
      This is because contaminated units may contain large numbers of virulent bacteria
      as well as endotoxins that are considered to be fatal to the recipient.
      Accordingly, measures have been proposed to prevent or at least control the
      potential risk of transfusion associated bacteria infections. Broadly, these
      approaches include: bacterial avoidance; bacterial growth inhibition and
      bacterial load reduction by leucofiltration/viral inactivation. Unfortunately,
      none of the current approaches alone or in combination have received overall
      acceptance in terms of operational practice and safety/efficacy. Considerable
      effort has also been directed towards improving bacterial detection in order to
      provide a scientific basis for the lengthening of the shelf life of liquid stored
      platelets, without affecting, to a large extent their safety/efficacy. These
      issues have been highlighted in this overview on the current status and future
      trends.

PMID- 15501420
TI  - Platelet function testing to assess the effectiveness of platelet transfusion
      therapy.

PMID- 15501421
TI  - Discontinuous automated calcium supplementation during thrombocytapheresis with
      the MCS+ version C. Absence of severe complication due to calcium deprivation in
      4308 procedures.

PMID- 15501422
TI  - Indomethacin, alone and combined with prochlorperazine and caffeine, but not
      sumatriptan, abolishes peripheral and central sensitization in in vivo models of
      migraine.
AB  - Recently it has been proposed that the throbbing pain of migraine is mediated by
      sensitization of peripheral trigeminovascular neurons, and that cutaneous
      allodynia of migraine is mediated by sensitization of central trigeminovascular
      neurons, and, moreover, that the triptans are less effective in aborting a
      migraine attack if the central sensitization is already established. The
      combination of indomethacin, prochlorperazine, and caffeine (IndoProCaf) is a
      drug of well-established use in the acute treatment of migraine. The aim of this
      study was to investigate whether the 3 active principles of IndoProCaf, alone and
      combined, compared to sumatriptan, were able to abolish the peripheral
      sensitization induced by kainic acid and the central sensitization induced by N
      methyl-D-aspartate (NMDA) in in vivo models of hyperalgesia. The study showed
      that indomethacin or IndoProCaf is able to abolish both the kainic acid-induced
      and the NMDA-induced hyperalgesia. If administered at different times, IndoProCaf
      was always effective in reversing the kainic acid-induced hyperalgesia.
      Sumatriptan was not able to reverse either the kainic acid-induced or the NMDA
      induced hyperalgesia. The efficacy of indomethacin, alone and combined with
      prochlorperazine and caffeine, in abolishing peripheral and central sensitization
      in in vivo models of hyperalgesia is a further explanation of the clinical
      efficacy of IndoProCaf in the treatment of migraine. PERSPECTIVE: This study
      suggests that, although triptans were shown to be able to abort migraine attacks
      only if given before the establishment of cutaneous allodynia and central
      sensitization, IndoProCaf should be able to abort migraine attacks independently
      from the time of administration, because it is able to abolish an already
      established peripheral and central sensitization.

PMID- 15501423
TI  - Nociception and antinociception during the first week of life in mice: sex
      differences and test dependence.
AB  - This study demonstrates that reliable sex differences in nociceptive and
      antinociceptive mechanisms are present in even very young subjects. Sex
      differences were observed in mice tested either on the day of birth or 1 week
      later on basal tail-flick latency and morphine analgesic magnitude. Female mice
      had longer tail-withdrawal latencies; male mice demonstrated stronger analgesic
      responses to morphine. In addition, basal pain behavior and analgesic
      responsiveness differed between day-old and week-old animals on the hot plate,
      with day-old mice showing enhanced pain behavior and reduced morphine
      antinociception compared to week-old subjects. These findings further support the
      competence of pain processing circuitry in even very young subjects and highlight
      the early development of nociceptive and antinociceptive mechanisms. PERSPECTIVE:
      This study highlights the competence of nociceptive circuitry and the analgesic
      efficacy of morphine as early as the day of birth in mice, reinforcing the
      importance of evaluating and treating pain in even the youngest subjects. Sex
      differences were present, suggesting infant sex as one of several potential
      factors that predict the experience of procedural or pathological pain and
      analgesic requirement.

PMID- 15501424
TI  - Results of the Leeds assessment of neuropathic symptoms and signs pain scale in
      Turkey: a validation study.
AB  - Classification of pain and identification of the specific pain mechanisms through
      utilization of clinical data are helpful to the physician in choosing the
      appropriate treatment model. For discrimination between different pain types,
      various tests could be used. The Leeds Assessment of Neuropathic Symptoms and
      Signs (LANSS) Pain Scale is a scale based on the analysis of data obtained during
      bedside examination. The LANSS Pain Scale, as first used by Bennett, is a very
      useful tool that provides immediate information in the clinical setting and helps
      distinguish nociceptive pain from neuropathic pain. In this study we targeted
      validation of the LANSS Pain Scale in the Turkish population. A total of 104
      patients who consulted the Algology Department of Istanbul Faculty of Medicine
      Outpatient Clinic were enrolled in our validation study. The sensitivity and
      specificity of the scale were found to be 89.9% and 94.2%, respectively. These
      results suggest a high validity level for the Turkish version of the LANSS Pain
      Scale. We believe that this scale is a useful tool for the differential diagnosis
      of neuropathic pain and can be used in future pharmacologic studies. PERSPECTIVE:
      Any measures that aid in differentiating neuropathic pain from nociceptive pain
      would facilitate effective management of pain. In daily practice the simplicity
      of the classification method is important. The present study suggests that
      Turkish version of LANSS can be used for the discrimination between neuropathic
      and nociceptive types of pain.

PMID- 15501425
TI  - Associations among pain intensity, sensory characteristics, affective qualities,
      and activity limitations in patients with chronic pain: a momentary, within
      person perspective.
AB  - The purpose of this article is to explore the multidimensionality of the pain
      experience for patients with chronic pain by using a within-person, longitudinal
      approach. An Ecological Momentary Assessment design with a patient electronic
      diary was used to collect random momentary pain assessments several times a day
      for 2 weeks. We examined the within-person relationships between pain intensity,
      sensory characteristics, affective qualities, and activities limited by pain. All
      3 dimensions (sensory, affective, and activities) were significantly related to
      pain intensity in a monotonic, but nonlinear, manner. These results expand our
      understanding of the pain experience by showing that changes of pain over time
      are associated with changes in sensory symptoms, affective distress, and activity
      limitations. PERSPECTIVE: Although the relationships between pain dimensions have
      been examined between people, the results have been interpreted as within
      persons. This article confirms that pain intensity is significantly related to
      sensory characteristics of pain, affective qualities of pain, and activity
      limitations due to pain within a person.

PMID- 15501426
TI  - Neonatal hind paw injury alters processing of visceral and somatic nociceptive
      stimuli in the adult rat.
AB  - Tissue damage during the first few weeks after birth can have profound effects on
      sensory processing in the adult. We have recently reported that a short-lasting
      inflammation of the neonatal rat hind paw produces baseline hypoalgesia and
      exacerbated hyperalgesia after reinflammation of that hind paw in the adult.
      Because the contralateral hind paw and forepaws also displayed hypoalgesia, we
      speculated that effects of the initial injury were not somatotopically restricted
      and would alter visceral sensory processing as well. In the present study we
      tested this hypothesis by examining the effects of neonatal hind paw injury at P3
      or P14 on visceral and somatic sensitivity in the adult rat. In P3 rats, the
      visceromotor response evoked by colorectal distention in the absence of colonic
      inflammation was attenuated in carrageenan-treated neonatal rats compared to
      naive rats. Colonic inflammation in the adult reversed this hypoalgesia and
      evoked a level of visceral hyperalgesia similar to naive rats. There were no
      consequences of the P14 injury observed in the adult. In a second experiment,
      colonic inflammation in naive rats induced viscerosomatic inhibition to thermal
      stimulation of the forepaw and hind paw. This inhibition was reversed, and the
      paw withdrawal latency was slightly decreased in neonatal (P3) carrageenan
      treated rats. Rats treated on P14 appeared similar to naive rats. These data
      support the hypothesis that neonatal hind paw injury during a critical period
      permanently alters sensory processing of multiple sensory modalities in the
      adult. Animals develop with greater inhibitory processing of somatic and visceral
      stimuli throughout the neuraxis. However, inflammation in the adult in previously
      uninjured tissue reverses the hypoalgesia and evokes development of normal
      hyperexcitability associated with tissue injury. PERSPECTIVE: Trauma experienced
      by premature infants can lead to alterations in sensory processing throughout
      life. This study shows that short-term somatic tissue injury to neonatal rats
      during a well-defined critical period alters several aspects of viscerosensory
      processing in the adult, demonstrating that injury to one tissue affects sensory
      processing throughout the body.

PMID- 15501427
TI  - Sex differences in responses to epidural steroid injection for low back pain.
AB  - Sex differences in clinical and experimental pain responses have been widely
      reported; however, few studies have examined sex differences in outcomes from
      interventional pain treatment and the predictors thereof. The aims of this study
      were to examine sex differences in (1) the acute pain produced by epidural
      steroid injections (ESIs), (2) clinical improvements in pain and pain-related
      psychological distress and disability after ESIs, and (3) predictors of the
      clinical response to ESIs. A total of 57 patients (37 menopausal women and 20
      men), seen in the pain clinic of a regional medical center for ESI therapy,
      participated. Patients rated the painfulness of the ESI procedure itself. Also,
      clinical pain, depression, and disability were assessed before treatment and at 2
      weeks and 2 months after the ESIs. Participants also were queried about their
      expectations of successful pain relief, coping strategies, and pain-related
      anxiety, which were examined as predictors of treatment outcome. Men reported
      significantly greater pain intensity and unpleasantness than women for the first
      injection only. All groups showed significant reductions in clinical pain,
      depression, and disability at 2 weeks compared to baseline, but minimal change
      occurred between 2 weeks and 2 months past baseline. No sex differences in the
      magnitude of treatment response emerged; however, specific dimensions of pain
      coping were associated with treatment responses in a sex-dependent manner. These
      findings suggest that the determinants of ESI pain and treatment outcome might
      differ across sex. PERSPECTIVE: Sex-related influences on pain responses have
      been widely reported, but few studies have explored sex-dependent predictors of
      treatment response. These findings indicate that pain coping was differentially
      associated with outcomes after ESI in women versus men.

PMID- 15501428
TI  - Fear-induced hypoalgesia in humans: effects on low intensity thermal stimulation
      and finger temperature.
AB  - Prior research indicates that exposure to fear-inducing stimuli inhibits finger
      withdrawal to sudden onset and high intensity radiant heat in humans. Although
      withdrawal latencies to intense heat are thought to reflect changes in spinal
      nociceptive processing, supraspinal measures are needed to determine whether pain
      perception is altered. The present study used gradual onset and low intensity
      radiant heat to induce a finger withdrawal response that depends on supraspinal
      processes. After baseline pain threshold tests, 57 healthy human participants
      were randomly assigned to 1 of 2 groups. In the fear group, participants received
      3 brief shocks. In the neutral group, participants did not receive shock. Results
      suggest that finger withdrawal latencies to low intensity heat were increased
      after shock presentation, providing additional evidence that fear reduces pain on
      a measure that is influenced by supraspinal processes. Both self-report and
      physiological (skin conductance level, heart rate, and blood pressure) measures
      of emotion confirmed that the intended affective states were induced. Finger
      temperature was unaffected by emotion manipulations; thus, skin cooling does not
      appear to mediate increased withdrawal latencies. These findings provide
      additional evidence that fear not only inhibits spinal nociceptive reflexes, it
      also inhibits supraspinal measures of pain. PERSPECTIVE: From a clinical
      perspective, these data suggest that patients who experience intense fear in
      response to unpredictable threatening events will show a reduction in pain
      perception.

PMID- 15501429
TI  - Cytochrome P450 expression in human keratinocytes: an aryl hydrocarbon receptor
      perspective.
AB  - The goal of this review is to stress the importance of the cytochrome P450 (CYP)
      superfamily that is expressed in human skin in the hope that it may stimulate
      further study in an intriguing topic that currently suffers from a relative
      dearth of information. Like the cells that line the respiratory and GI tracts [X.
      Ding, L.S. Kaminsky, Human extrahepatic cytochromes P450: function in xenobiotic
      metabolism and tissue-selective chemical toxicity in the respiratory and
      gastrointestinal tracts, Annu. Rev. Pharmacol. Toxicol. 43 (2003) 149-173] those
      present in human skin express a variety of CYPs that play important roles in
      xenobiotic, drug and steroid metabolism. In addition, a few CYPs, with
      potentially novel roles in metabolism and keratinocyte function, have recently
      been discovered that appear to be expressed in a keratinocyte-specific manner [L.
      Du, S.M. Hoffman, D.S. Keeney, Epidermal CYP2 family cytochromes P450, Toxicol.
      Appl. Pharmacol. 195 (2004) 278-287]. However, in preparing this review, it soon
      became apparent that in contrast to the progress made in understanding these
      events in the liver, relatively little is known in the human skin. Thus, while a
      number of tantalizing stories are beginning to emerge, they are far from
      complete. In this review, a brief synopsis of the structure of skin and methods
      of culturing keratinocytes will be presented. This will be followed by an
      overview of the various CYPs and their putative regulators that have been
      currently identified to be expressed in human keratinocytes. Then, a more
      detailed analysis of CYP regulation that involves the aryl hydrocarbon receptor
      (AHR) signaling pathway will be offered in the hope that it may serve as a
      paradigm for other CYP regulatory studies in the skin. Finally, several clinical
      implications that may arise due to altered regulation of CYPs will be considered.

PMID- 15501430
TI  - Therapeutic efficacy of green tea polyphenols on cellular thiols in 4
      Nitroquinoline 1-oxide-induced oral carcinogenesis.
AB  - In cancer, a high flux of oxidants not only depletes the cellular thiols, but
      damages the whole cell as well. Epidemiological studies suggest green tea may
      mitigate cancers in human and animal models for which several mechanisms have
      been proposed. In the present investigation, the levels of cellular thiols such
      as reduced glutathione (GSH), oxidised glutathione (GSSG), protein thiols (PSH),
      total thiols, lipid peroxidation product conjugated dienes and the activity of
      gamma glutamyl transferase (GGT) were assessed in tongue and oral cavity. In 4
      Nitroquinoline 1-oxide- (4-NQO) induced rats, there was a decrease in the levels
      of GSH, PSH and total thiols and an increase in the levels of GSSG, conjugated
      dienes and the activity of GGT. On supplementation of green tea polyphenols (GTP)
      for 30 days (200 mg/kg) for the oral cancer-induced rats, there was a moderate
      increase in the levels of GSH, PSH and total thiols and a decrease in the levels
      of GSSG, conjugated dienes and the activity of GGT. Thus, GTP reduces the oxidant
      production thereby maintains the endogenous low molecular weight cellular thiols
      in oral cancer-induced rats. From the results, it can be concluded that GTP
      supplementation enhances the cellular thiol status thereby mitigate oral cancer.

PMID- 15501431
TI  - Insulinomimetic effects of kaempferitrin on glycaemia and on 14C-glucose uptake
      in rat soleus muscle.
AB  - Bauhinia forficata is one of the Bauhinia species mostly used as an antidiabetic
      herbal remedy in Brazil. Kaempferitrin (kaempferol-3,7-O-(alpha)-L-dirhamnoside)
      is the predominant flavonol glycoside found in the B. forficata leaves. The aim
      of the present work was to study the long-term effect of kaempferitrin on
      glycaemia in diabetic rats, as well as the in vitro effect of this compound on
      14C-D-glucose uptake and 14C-leucine incorporation into protein in normal rat
      soleus muscle. Kaempferitrin was found to have an acute lowering effect on blood
      glucose in diabetic rats and to stimulate the glucose uptake percentile, as
      efficiently as insulin in muscle from normal rats. This compound did not have any
      effect on glucosuria or on protein synthesis in muscle from normal and diabetic
      animals. However, the protein synthesis in the kaempferitrin-treated groups was
      maintained at the same level as the respective controls. Thus, the hypoglycaemic
      effect and the prompt efficiency of the kaempferitrin in stimulating [U-14C]-2
      deoxi-D-glucose uptake in muscle -constitute the first evidence to indicate that
      the acute effect of this compound on blood glucose lowering may occur as a
      consequence of the altered intrinsic activity of the glucose transporter (Vmax or
      glucose transporters translocation?) not involving directly the synthesis of new
      carriers.

PMID- 15501432
TI  - Antioxidant enzymes and thiol/disulfide status in the digestive gland of the
      brown mussel Perna perna exposed to lead and paraquat.
AB  - Lead (Pb) and paraquat (PQ) have different toxic mechanisms associated with cell
      damage. Pb may induce alterations in zinc containing proteins, including the
      known inhibitory effect on the enzyme delta-aminolevulinic acid dehydratase,
      disrupting the heme-synthesis pathway. During PQ biotransformation, redox cycle
      reactions enhance oxyradical production, which may lead to pro-oxidative
      conditions. In this study, we analyzed the effects of Pb and PQ on antioxidant
      enzymes and thiol status, using the digestive glands of the mussel Perna perna
      collected in a mussel farm on Santa Catarina Island. Mussels were exposed to Pb
      (1 ppm) and PQ (10 ppm), either separately or concomitantly, for 48 h. We were
      unable to detect an effect of Pb treatment on the enzymes, catalase, glucose 6
      phosphate dehydrogenase (G6PDH), glutathione S-transferase (GST) and glutathione
      reductase (GSSG-reductase), which contrasts to the effect of PQ, increasing GSSG
      reductase and G6PDH, but decreasing GST activity. The thiol status showed a pro
      oxidative trend, observed mainly through a decrease in the reduced/oxidized
      glutathione ratio, despite the total-glutathione increase. Protein-mixed
      disulfides and protein thiols did not change by the treatments. The observed
      effects of PQ and Pb were consistent with literature. Pb had a suppressive effect
      on the enzymatic changes elicited by PQ, while the changes in the thiol/disulfide
      parameters were retained.

PMID- 15501433
TI  - Induction of c-fos messenger RNA by 3-(N-phenylamino)-1,2-propanediol esters,
      compounds related to Toxic Oil Syndrome.
AB  - The Toxic Oil Syndrome (TOS) was a toxic epidemic disease, related to the
      consumption of rapeseed oil denatured with aniline that affected more than 20,000
      people in Spain and resulted in more than 330 deaths after its sudden appearance
      in 1981. It has been reported that the fatty acid esters of 3-(N-phenylamino)-1,2
      propanediol (PAP) have shown a strong association with TOS. These PAP-esters
      could be absorbed and metabolized in a similar way than phospholipids. This is of
      interest because some products of phospholipid metabolism are important mediators
      in downstream pathways involved in the regulation of different nuclear factors.
      In particular, phospholipase D activity is involved in the activation of c-fos.
      Thus, we have investigated the effect of different PAP-esters in the induction of
      c-fos in lung fibroblasts. Results indicate that PAP-esters rapidly induced the
      expression of c-fos in a dose-dependent manner. In addition, both butanol and
      propranolol prevent this induction pointing to the involvement of phospholipase D
      in this activation. These results suggest that deregulation of some nuclear
      factors such as AP-1 could be involved in the pathogenesis of TOS.

PMID- 15501434
TI  - Effect of cadmium on cell cycle progression in Chinese hamster ovary cells.
AB  - Chinese hamster ovary K1 (CHO K1) cells are very sensitive to cadmium (Cd)
      toxicity. They were used to investigate the effect of Cd on cell cycle
      progression. Cells were cultured with 0.1, 0.4, 1 or 4 microM Cd for various time
      intervals. There was no difference in growth rate when less than 0.4 microM Cd
      was given within 24 h. A dose-dependent reduction of cell proliferation was
      observed when more than 0.4 microM of Cd was given. The cells were pulse-labeled
      with 5-bromodeoxyuridine (BrdU), and the labeled cells were cultured in the
      presence of increasing concentrations of Cd. Cell cycle progression was retarded
      as a function of Cd concentration. G2/M arrest was observed when the BrdU-labeled
      cells were treated with 1 microM Cd for 8h, whereas cells receiving 4 microM Cd
      stopped at the S phase within 4 h. Cell cycle analysis of cells treated with Cd
      for 24 h showed that G2/M arrest occurred only when cells received 0.8 to 2
      microM Cd. Despite the occurrence of G2/M arrest in the Cd treatment, only a
      limited proportion of the cells were blocked in the M phase. However, the
      increase in M phase cells coincided with an elevation in the cyclin-dependent
      kinase 1 activity. To examine whether Cd acts on cells at a specific cell stage,
      they were synchronized at the G1 or G2/M phase then treated with 1 microM Cd for
      12 h. The cells were blocked at the G2/M and G1/S phase, respectively. This
      finding indicates that Cd toxicity is global and not cell phase specific. We also
      investigated the involvement of Cd-induced reactive oxygen species (ROS) with the
      occurrence of G2/M block and found a lack of correlation between cell cycle
      arrest and ROS production. We measured the Cd content that caused G2/M arrest
      from a series of Cd treatments and determined the ranges of cumulative Cd
      concentrations that could result in cell cycle arrest.

PMID- 15501435
TI  - Genotoxicity of acrylamide in human lymphocytes.
AB  - Acrylamide is used in the industry and can be a by-product in a high-temperature
      food processing. It is reported to interact with DNA, but the mechanism of this
      interaction is not fully understood. In the present study, we investigated the
      DNA-damaging potential of acrylamide (ACM) in normal human lymphocytes using the
      alkaline-, neutral- and 12.1 versions of the comet assay and pulsed-field gel
      electrophoresis. We also investigated effect of acrylamide on caspase-3 activity
      as well as its influence on the repair process of hydrogen peroxide-induced DNA
      damage. Acrylamide at 0.5-50 microM induced mainly alkali-labile sites. This
      damage was repaired during a 60-min repair incubation. Post-treatment of the
      damaged DNA with repair enzymes: thymine glycol DNA N-glycosylase (Nth) and
      formamidopyrimidine-DNA glycosylase (Fpg), recognizing oxidized DNA bases, as
      well as 3-methyladenine-DNA glycosylase II (Alk A), recognizing alkylated bases,
      caused an increase in the extent of DNA damage, indicating the induction of
      oxidative and alkylative DNA base modifications by acrylamide. Pre-treatment of
      the lymphocytes with N-tert-butyl-alpha-phenylnitrone (PBN), a spin trap, as well
      as vitamins C and E decreased the DNA-damaging effect of acrylamide, which
      suggest that free radicals/reactive oxygen species may be involved in this
      effect. Acrylamide impaired the repair of DNA damaged by hydrogen peroxide and
      increased the activity of caspase-3, which may indicate its potential to induce
      apoptosis. Our results suggest that acrylamide may exert a wide spectrum of
      diverse effects on DNA of normal cells, including mostly DNA base modifications
      and apoptosis. Acrylamide may also impair DNA repair. Free radicals may underline
      these effects and some dietary antioxidants can be considered as protective
      agents against genotoxic action of acrylamide. As normal lymphocytes contain
      cyp2e1 and P450, engaged in the bioactivation of ACM to glicidamide it is
      uncertain whether acrylamide causes all of measured effect per se or this is the
      result of the action of its metabolites.

PMID- 15501436
TI  - Metabolic fate of the Ah receptor ligand 6-formylindolo[3,2-b]carbazole.
AB  - The physiological role of the aryl hydrocarbon receptor (AhR), a member of the
      basic helix-loop-helix PER-ARNT-SIM (PAS) transcription factor family is not
      known. We have suggested that the AhR is involved in light signaling through
      binding of photoproducts with high AhR affinity. This suggestion is based on (i)
      the high AhR affinity of the tryptophan photoproduct formylindolo[3,2-b]carbazole
      (FICZ), (ii) the induction of rapid and transient expression of AhR-regulated
      genes by FICZ and by extracts of UV-irradiated tryptophan as well as (iii) the
      fact that light induces the AhR-regulated cytochrome P450s CYP1A1, CYP1B1 and
      CYP2S1. The transient mRNA expression caused by light and tryptophan
      photoproducts suggests that the biotransformation enzymes induced by AhR
      activation take part in a metabolic degradation of the natural AhR ligand. This
      study aimed at identifying the involvement of phase I and phase II enzymes in the
      metabolic degradation of FICZ. A cytochrome P450-dependent metabolism of FICZ
      giving rise to preferentially mono- and di-hydroxylated derivatives has earlier
      been reported. In the present study, rat and human hepatic S9 mixes were employed
      together with specific enzyme inhibitors and cofactors. Compared to the Aroclor
      induced rat liver S9, the non-induced rat liver S9 and the human liver S9 caused
      a more complex metabolite profile of FICZ. The CYP1A1 enzyme was confirmed to be
      the most important enzyme for the first step in the metabolism. CYP1A2 was found
      to have overlapping specificity with CYP1A1 being able to form the same major
      metabolites although with different kinetics. CYP1B1 turned out to be
      preferentially involved in the further metabolism of dihydroxylated metabolites.
      Microsomal epoxide hydrolase, and as yet not identified forms of
      sulphotransferases and glucuronosyltransferases were also found to take part in
      the metabolic degradation of FICZ. Thus, tryptophan photoproducts fit into a
      model in which the ligand-activated AhR signaling is autoregulated by the induced
      metabolic enzymes.

PMID- 15501437
TI  - Microtubule-interfering activity of parthenolide.
AB  - Parthenolide is an active sesquiterpene lactone present in a variety of medicinal
      herbs, well known as anti-inflammatory drug. It has recently been proposed as a
      chemotherapeutic drug, but the pharmacological pathways of its action have not
      yet been fully elucidated. Firstly, we explored whether the anticancer properties
      of parthenolide may be related to a tubulin/microtubule-interfering activity. We
      additionally compared bioactivities of parthenolide with those checked after
      combined treatments with paclitaxel in human breast cancer MCF-7 cells.
      Parthenolide exerted in vitro stimulatory activity on tubulin assembly, by
      inducing the formation of well-organized microtubule polymers. Light microscopy
      detections showed that parthenolide-induced alterations of either microtubule
      network and nuclear morphology happened only after combined exposures to
      paclitaxel. In addition, the growth of MCF-7 cells was significantly inhibited by
      parthenolide, which enhanced paclitaxel effectiveness. In conclusion, the
      antimicrotubular and antiproliferative effects of parthenolide, well known
      microtubule-stabilizing anticancer agent, may influence paclitaxel activity. The
      tubulin/microtubule system may represent a novel molecular target for
      parthenolide, to be utilized in developing new combinational anticancer
      strategies.

PMID- 15501438
TI  - Desmin: a major intermediate filament protein essential for the structural
      integrity and function of muscle.
AB  - Desmin is a muscle-specific protein and a key subunit of the intermediate
      filament in cardiac, skeletal and smooth muscles. Desmin filaments are mainly
      located at the periphery of Z-disk of striated muscles and at the dense bodies of
      smooth muscle cells, and they have been postulated to play a critical role in the
      maintenance of structural and mechanical integrity of the contractile apparatus
      in muscle tissues. This review summarizes the findings in the regulation of the
      desmin gene and function of the desmin protein. The expression of desmin gene is
      regulated by a combination of different transcription control regions in muscle
      cells. The results from mice deficient in desmin reveal the fundamental role of
      desmin filaments in cell architecture, force transmission and mitochondrial
      function. Mice lacking desmin postnatally develop a dilated cardiomyopathy, a
      skeletal myopathy and smooth muscle defects. Some of desmin-related myopathies
      are attributable to a missense mutations and deletions in the desmin gene. Other
      desmin-related myopathies, in which the desmin gene is not mutated, could be
      related to mutations of the genes encoding the proteins that interact with
      desmin.

PMID- 15501439
TI  - Closing the loops: new insights into the role and regulation of actin during cell
      polarization.
AB  - In this review, we summarize recent results on the understanding of actin
      organization and cell polarization with an emphasis on the critical role of actin
      during this process. We first report on the advances made in understanding the
      function and mechanism of formin family proteins in the nucleation of actin
      filaments. We also discuss how formins and other regulators of actin dynamics are
      thought to be involved in the generation of cell polarity. In the second part we
      discuss new findings indicating that, rather than using a linear pathway from
      signal transduction to cytoskeleton re-organization, cell polarity is established
      through bidirectional interplay between these processes. We describe the various
      types of feedback loops identified and point out common schemes. Finally we
      briefly summarize the emerging role of actinlike proteins in the generation of
      polarity in prokaryotes that implies an early origin of actin's role in cell
      polarity.

PMID- 15501440
TI  - Formins: processive cappers of growing actin filaments.
AB  - Taking the advantage of single-molecule imaging, our recent study has revealed
      surprisingly long processive movement of a Formin protein, mDia1, surfing along
      with the growing end of actin filaments in living cells. This finding provides
      direct evidence for the ability of Formins to function as processive cappers that
      has been postulated from several lines of evidence in biochemical studies. With
      nucleating filaments from the profilin-actin pool, Formins may effectively
      generate long actin filaments, and contribute to the generation of the specific
      actin-based structures, that is, the contractile ring in cytokinesis, actin
      stress fibers in animal cells, and yeast actin cables. Furthermore, Formins have
      the potential to function as actin polymerization-driven molecular motors.
      Although much remains to be tested about the role of this novel molecular
      mobilization mechanism, cells might utilize actin polymerization energy for cell
      shape change and/or trafficking via Formin motors.

PMID- 15501442
TI  - Guiding cell migration through directed extension and stabilization of
      pseudopodia.
AB  - Cell migration requires establishment of a single pseudopodium in the direction
      of movement. Here we highlight recent advances in our understanding of the
      molecular signaling mechanisms that regulate formation of pseudopodia. We discuss
      how signal transduction processes are spatially and temporally organized to
      establish cell polarity through directed extension and stabilization of dominant
      pseudopodia. We also highlight recent advances in technology that will further
      the understanding of signaling dynamics specific to pseudopodia extension and
      cell migration.

PMID- 15501441
TI  - Global cytoskeletal control of mechanotransduction in kidney epithelial cells.
AB  - Studies of mechanotransduction mediated by stress-sensitive ion channels
      generally focus on the site of force application to the cell. Here we show that
      global, cell-wide changes in cytoskeletal structure and mechanics can regulate
      mechanotransduction previously shown to be triggered by activation of the
      mechanosensitive calcium channel, polycystin-2, in the apical primary cilium of
      renal epithelial cells [S.M. Nauli, F.J. Alenghat, Y. Luo, E. Williams, P.
      Vassilev, X. Li, A.E. Elia, W. Lu, E.M. Brown, S.J. Quinn, D.E. Ingber, J. Zhou,
      Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney
      cells. Nat. Genet. 33 (2003) 129-37]. Disrupting cytoplasmic microfilaments or
      microtubules in these cells eliminated fluid shear stress-induced increase of
      intracellular calcium. Altering the cytoskeletal force balance by inhibiting
      actomyosin-based tension generation (using 2,3-butanedione monoxime), interfering
      with microtubule polymerization (using nocodazole, cochicine, or taxol), or
      disrupting basal integrin-dependent extracellular matrix adhesions (using soluble
      GRGDSP peptide or anti-beta1 integrin antibody), also inhibited the calcium spike
      in response to fluid stress. These data indicate that although fluid stress
      induced displacement of the primary cilium may be transduced into a calcium spike
      through activation of polycystin-2 and associated calcium-induced calcium release
      from intracellular stores, this mechanotransduction response is governed by
      global mechanical cues, including isometric tension (prestress) within the entire
      cytoskeleton and intact adhesions to extracellular matrix.

PMID- 15501443
TI  - New insights into the structural organization of eukaryotic and prokaryotic
      cytoskeletons using cryo-electron tomography.
AB  - Cryo-electron tomography (cryo-ET) is an emerging imaging technology that
      combines the potential of three-dimensional (3-D) imaging at molecular resolution
      (<5 nm) with a close-to-life preservation of the specimen. In conjunction with
      pattern recognition techniques, it enables us to map the molecular landscape
      inside cells. The application of cryo-ET to intact cells provides novel insights
      into the structure and the spatial organization of the cytoskeleton in
      prokaryotic and eukaryotic cells.

PMID- 15501444
TI  - Why three Rho proteins? RhoA, RhoB, RhoC, and cell motility.
AB  - Higher vertebrates have 3 Rho GTPases, RhoA, RhoB, and RhoC, which share 85%
      amino acid sequence identity. Here, we compare and contrast the roles of RhoA, B,
      and C in the regulation of the cytoskeleton and cell motility. Despite their
      similarity, some regulators and effectors show preferential interaction with
      RhoA, B, or C, and the three proteins show differences in function in cells. RhoA
      plays a key role in the regulation of actomyosin contractility. RhoB, which is
      localized primarily on endosomes, has been shown to regulate cytokine trafficking
      and cell survival, while RhoC may be more important in cell locomotion. In cancer
      cells, the expression and activity of RhoA, B, and C is altered in different
      ways. Together, this evidence suggests that although the 3 isoforms of Rho are
      structurally highly homologous, they have different cellular functions.

PMID- 15501445
TI  - Kinesin superfamily proteins and their various functions and dynamics.
AB  - Kinesin superfamily proteins (KIFs) are motor proteins that transport membranous
      organelles and macromolecules fundamental for cellular functions along
      microtubules. Their roles in transport in axons and dendrites have been studied
      extensively, but KIFs are also used in intracellular transport in general. Recent
      findings have revealed that in many cases, the specific interaction of cargoes
      and motors is mediated via adaptor/scaffolding proteins. Cargoes are sorted to
      precise destinations, such as axons or dendrites. KIFs also participate in
      polarized transport in epithelial cells as shown in the apical transport of
      annexin XIIIb-containing vesicles by KIFC3. KIFs play important roles in higher
      order neuronal activity; transgenic mice overexpressing KIF17, which transports N
      methyl-d-asp (NMDA) receptors to dendrites, show enhanced memory and learning.
      KIFs also play significant roles in neuronal development and brain wiring: KIF2A
      suppresses elongation of axon collaterals by its unique microtubule
      depolymerizing activity. X-ray crystallography has revealed the structural
      uniqueness of KIF2 underlying the microtubule-depolymerizing activity. In
      addition, single molecule biophysics and optical trapping have shown that the
      motility of monomeric KIF1A is caused by biased Brownian movement, and X-ray
      crystallography has shown how the conformational changes occur for KIF1A to move
      during ATP hydrolysis. These multiple approaches in analyzing KIF functions will
      illuminate many basic mechanisms underlying intracellular events and will be a
      very promising and fruitful area for future studies.

PMID- 15501446
TI  - Aurora kinases in spindle assembly and chromosome segregation.
AB  - The Aurora kinase family consists of three members, Aurora A, B, and C. The
      Aurora A and B kinases have emerged as essential regulators of cell division.
      While Aurora A kinase is implicated in regulating mitotic entry, centrosome
      maturation, and spindle assembly, Aurora B is required for correct chromosome
      segregation and cytokinesis. In this review, we summarize the roles of Aurora A
      and B in spindle assembly and chromosome segregation.

PMID- 15501447
TI  - Intermediate filaments and tissue repair.
AB  - Intermediate filaments (IFs), along with microtubules and microfilaments,
      comprise the organized, cytoplasmic networks commonly called the cytoskeleton. A
      large multigene family (>67) encodes proteins able to self-assemble into 10- to
      12-nm-wide IFs in the cytoplasm and nucleus. Individual genes are regulated in a
      tissue-, cell type-, and context-dependent fashion, the significance of which is
      not yet understood. A major function fulfilled by all types of IFs is to
      contribute to the maintenance of cellular integrity in the presence of mechanical
      stress. Another emerging function is to act as a scaffold that binds and
      regulates the activity of several types of effector proteins, for example,
      receptors, kinases, adaptors, and heat shock proteins. Here we review the
      literature showing that modulation of cytoplasmic IFs occurs rapidly after injury
      to a variety of tissues and that such changes play an important role in the
      context of a timely repair response.

PMID- 15501448
TI  - Molecular mechanisms underlying the assembly of intermediate filaments.

PMID- 15501449
TI  - The cytoskeleton and epidermal morphogenesis in C. elegans.
AB  - During Caenorhabditis elegans development, the process of epidermal elongation
      converts the bean-shaped embryo into the long thin shape of the larval worm.
      Epidermal elongation results from changes in the shape of epidermal cells, which
      in turn result from changes in the epidermal cytoskeleton, the extracellular
      matrix, and in cell-matrix adhesion junctions. Here, we review the roles of
      cytoskeletal filament systems in epidermal cell shape change during elongation.
      Genetic and cell biological analyses have established that all three major
      cytoskeletal filament systems (actin microfilaments, microtubules, and
      intermediate filaments (IFs)) play distinct and essential roles in epidermal cell
      shape change. Recent work has also highlighted the importance of communication
      between these systems for their integrated function in epidermal elongation.
      Epidermal cells undergo reciprocal interactions with underlying muscle cells,
      which regulate the position and function of IF-containing cell-matrix adhesion
      structures within the epidermis. Elongation thus exemplifies the reciprocal
      tissue interactions of organogenesis.

PMID- 15501450
TI  - Emerging functions: diseases and animal models reshape our view of the
      cytoskeleton.
AB  - Intermediate filaments (IFs), desmosomes, and their associates are built from
      multidomain proteins that form cytoskeletal scaffolds in the cytoplasm and the
      nucleus of vertebrate tissues. Mutations in more than 80 genes cause monogenic
      disorders that include severe skin fragility, myopathies, neurodegeneration, and
      premature ageing, and contribute to polygenic disorders including liver and
      inflammatory bowel disease. First interpreted as "mechanical weakness" disorders
      resulting from a weakened cytoskeleton, emerging data support the concept that
      changes in cytoskeletal architecture profoundly alter signal transduction and
      cellular transcription patterns. This is in line with cell type-specific
      interactions between cytoskeletal and their associated proteins, and may involve
      both soluble and insoluble forms of intermediate filament proteins. Understanding
      how mutation-induced disruption of the cytoskeleton and its upstream regulators
      causes disease at the molecular level presents one of the major challenges in
      future research.

PMID- 15501451
TI  - Young children's sensitivity to probabilistic phonotactics in the developing
      lexicon.
AB  - A series of three experiments examined children's sensitivity to probabilistic
      phonotactic structure as reflected in the relative frequencies with which speech
      sounds occur and co-occur in American English. Children, ages 212 and 312 years,
      participated in a nonword repetition task that examined their sensitivity to the
      frequency of individual phonetic segments and to the frequency of combinations of
      segments. After partialling out ease of articulation and lexical variables, both
      groups of children repeated higher phonotactic frequency nonwords more accurately
      than they did low phonotactic frequency nonwords, suggesting sensitivity to
      phoneme frequency. In addition, sensitivity to individual phonetic segments
      increased with age. Finally, older children, but not younger children, were
      sensitive to the frequency of larger (diphone) units. These results suggest not
      only that young children are sensitive to fine-grained acoustic-phonetic
      information in the developing lexicon but also that sensitivity to all aspects of
      the sound structure increases over development. Implications for the acoustic
      nature of both developing and mature lexical representations are discussed.

PMID- 15501452
TI  - The role of crawling and walking experience in infant spatial memory.
AB  - This research explored infants' use of place learning and cue learning in a
      locomotor task across the transition from crawling to walking. Novice and expert
      crawling and walking infants were observed in a novel locomotor task-finding a
      hidden goal location in a large space. In Experiment 1, infants were tested with
      distal landmarks. Infants with fewer than 6 weeks of experience, either crawling
      or walking, could not find the goal location. All infants with more locomotor
      experience were more successful. Learning did not transfer across the transition
      to walking. In Experiment 2, novice and expert crawlers and walkers were tested
      with a direct landmark. Again, novice crawlers and walkers with fewer than 6
      weeks of experience could not find the goal, whereas those with more experience
      could. Taken together, these findings suggest that infants' spatial learning is
      inextricably linked to mode of locomotion.

PMID- 15501453
TI  - Testing the concurrent and predictive relations among articulation accuracy,
      speech perception, and phoneme awareness.
AB  - The relations among articulation accuracy, speech perception, and phoneme
      awareness were examined in a sample of 97 typically developing children ages 48
      to 66 months. Of these 97 children, 46 were assessed twice at ages 4 and 5 years.
      Children completed two tasks for each of the three skills, assessing these
      abilities for the target phoneme /r/ and the control phoneme /m/ in the word
      initial position. Concurrent analyses revealed that phoneme-specific relations
      existed among articulation, awareness, and perception. Articulation accuracy of
      /r/ predicted speech perception and phoneme awareness for /r/ after controlling
      for age, vocabulary, letter-word knowledge, and speech perception or phoneme
      awareness for the control phoneme /m/. The longitudinal analyses confirmed the
      pattern of relations. The findings are consistent with a model whereby children's
      articulation accuracy affects preexisting differences in phonological
      representations and, consequently, affects how children perceive, discriminate,
      and manipulate speech sounds.

PMID- 15501454
TI  - Gene therapy for sarcoma utilizing adenoviral transfer of the beta-glucuronidase
      and bax genes and an anthracyline prodrug.
AB  - BACKGROUND: When acted on by beta-glucuronidase (BG), HMR1826 is metabolized to
      doxorubicin. Use of this prodrug with adenoviral transfer of beta-glucuronidase
      (AdBG) is limited by the drug's inability to enter cells and intracellular
      retention of BG after transduction. We evaluated a system combining AdBG,
      transfer of the proapoptotic gene bax (AdBax) at a low multiplicity of infection,
      and HMR1826 administration. MATERIALS AND METHODS: Fibrosarcoma cells were
      treated with AdBG alone, AdBG plus HMR1826, AdBG followed by beta-galactosidase
      (AdLacZ) plus HMR1826, and AdBG followed by AdBax with no prodrug. In the
      experimental group, cells were transfected with AdBG, followed by AdBax plus
      HMR1826. Viability was measured 24 h after transfection and prodrug
      administration. Western blots for BG were performed on cell lysates and
      supernatants. RESULTS: Minimal cellular killing was noted in the AdBG alone, AdBG
      plus HMR 1826, or AdBG:AdLacZ plus HMR 1826 groups, and Western blot did not
      demonstrate BG in the supernatant even though all AdBG-transfected cell lysates
      were positive. Cell killing was noted in the AdBG:AdBax group, but less than in
      the AdBG:AdBax plus HMR 1826 group (without prodrug versus with prodrug: 1:1 to
      55.5% versus 75.9%, 5:1 to 10.0% versus 75.9%, 10:1 7.6% versus 49.0%, 20:1 4.6%
      versus 24.9%, P = 0.037). Western blot demonstrated BG in the supernatant of the
      AdBG:AdBax groups. CONCLUSIONS: We have devised a novel enzyme prodrug method of
      killing tumor cells and engendering a bystander effect. AdBax leads to BG release
      from dying cells after AdBG transduction and conversion of HMR1826 to an active
      anthracycline.

PMID- 15501455
TI  - Akt activation protects rat liver from ischemia/reperfusion injury.
AB  - BACKGROUND: Apoptosis as well as necrosis may play an important role in hepatic
      ischemia/reperfusion (I/R) injury. Akt, a serine-threonine protein kinase, is
      known to promote cell survival. We investigated whether gene transfer of
      constitutively active or dominant negative Akt could affect hepatic I/R injury.
      MATERIALS AND METHODS: Hepatic I/R injury was induced in rats by Pringle's
      maneuver for 20 min followed by reperfusion. Adenoviruses encoding a
      constitutively active form of Akt (myrAkt), a dominant negative form of Akt
      (dnAkt), or beta-galactosidase (LacZ) were injected through the tail vein 72 h
      before hepatic I/R. RESULTS: Terminal deoxynucleotidyl transferase-mediated dUTP
      biotin nick-end labeling (TUNEL) staining demonstrated a significant increase in
      the positive cells 240 min after reperfusion. Immunoblotting with phospho-Akt
      antibody showed phosphorylation of Akt from 90 to 180 min after reperfusion. The
      expression of myrAkt reduced the number of TUNEL-positive cells and hepatic
      necrosis around the central veins in the liver after reperfusion. This expression
      also significantly inhibited the increase in serum alanine aminotransferase (297
      +/- 131 IU/L, P < 0.05) 120 min after I/R, compared with increases in uninfected
      (1761 +/- 671 IU/L), LacZ adenovirus (1528 +/- 671 IU/L)-, and dnAkt adenovirus
      (1342 +/- 485 IU/L)-infected rats. MyrAkt expression phosphorylated Bad and
      inhibited the release of cytochrome-c after reperfusion. No difference in nuclear
      translocation of nuclear factor (NF)-kappaB, p65 was seen among the three groups
      of rats, however. CONCLUSION: Adenoviral gene transfer of myrAkt could inhibit
      apoptotic cell death and subsequent hepatic I/R injury in the rat, through Bad,
      not NF-kappaB.

PMID- 15501456
TI  - Curcumin inhibits mitogen stimulated lymphocyte proliferation, NFkappaB
      activation, and IL-2 signaling.
AB  - BACKGROUND: T cell mediated acute rejection of transplanted organ continues to be
      a noticeable problem in solid organ transplantation. We showed that Curcumin is a
      potent inhibitor of Cyclosporin A resistant T cell CD28 co-stimulation pathway.
      Here we report the inhibitory effects of Curcumin on mitogen-stimulated
      lymphocyte proliferation, IL-2 synthesis/signaling, and NFkappaB (transcription
      factor of IL-2 promoter) activation. MATERIALS AND METHODS: Human lymphocytes
      were isolated from fresh human spleen (SP-L). Mitogens [final concentrations of 2
      microg/ml concanavalin A (Con A), 5 microg/ml phytohemagglutinin (PHA), and 20
      ng/ml of phorbol-12-myristate-13-acetate (PMA)] were added to the designated
      wells in a 96-well plate with 0.2 million SP-L and cultured for 48 h and then
      assayed for IL-2 synthesis by ELISA and 3H-thymidine uptake. In another parallel
      experiment we added IL-2 (0.5 nM) to stimulate the cells to check if Curcumin's
      inhibition of IL-2 synthesis is the sole reason for inhibition of cell
      proliferation. Electrophoretic mobility shift assay (EMSA) was performed in PMA
      (20 ng/ml, 1 h) stimulated cells with or without Curcumin to assay NFkappaB
      activation. RESULTS: Curcumin at 2.5 microg/ml inhibited Con A, PHA, and PMA
      stimulated SP-L proliferation at 77, 23, and 48%, respectively, over controls and
      Curcumin at 5 microg/ml completely (nearly 100%) inhibited the mitogen stimulated
      proliferation. Curcumin inhibited IL-2 synthesis in Con A, PHA, and PMA
      stimulated SP-L in a concentration-dependent manner with an ED50 (concentration
      required for 50% inhibition) measured at 3.5 microg/ml. Exogenous IL-2 stimulated
      SP-L proliferation was also inhibited by Curcumin in a concentration-dependent
      manner with an ED50 of 2 microg/ml. EMSA assay indicated that PMA at 20 ng/ml
      stimulated NFkappaB activation 253% over control, which was inhibited by 24, 38,
      and 73%, respectively, with Curcumin at final concentrations of 2.5, 5, and 10
      microg/ml, respectively. CONCLUSION: Curcumin has profound immunosuppressive
      effects mediated via inhibition of IL-2 synthesis, mitogen, and IL-2 induced
      activation of human lymphocytes. This effect may be mediated via NFkappaB
      inhibition.

PMID- 15501457
TI  - Cecal ligation and puncture with total parenteral nutrition: a clinically
      relevant model of the metabolic, hormonal, and inflammatory dysfunction
      associated with critical illness.
AB  - BACKGROUND: Standard rat cecal ligation and puncture (CLP) results in only
      transient hyperglycemia, making an examination of the effects of glucoregulatory
      agents, such as insulin, on the morbidity and mortality of CLP problematic.
      Accordingly, we sought to develop a model of rat CLP with prolonged hyperglycemia
      through continuous infusion of total parenteral nutrition (TPN) post CLP.
      MATERIALS AND METHODS: Polyethylene catheters were implanted into the femoral
      vein of female Sprague Dawley rats (245-265 g) which were subsequently subjected
      to CLP. TPN was initiated at different intervals following CLP, and mortality,
      bacteremia, blood glucose, hormonal, and inflammatory responses were monitored.
      RESULTS: Without TPN, CLP resulted in significantly lower blood glucose at 22 h
      post CLP. In contrast, CLP rats receiving TPN exhibited significant prolonged
      hyperglycemia that was responsive to insulin treatment. Mortality and
      hyperglycemia tended to increase with puncture size in CLP TPN rats, with early
      initiation of TPN leading to poorer outcome. There were time-dependent
      differences in bacteremia and mortality based on time of TPN initiation. Levels
      of insulin, leptin, and glucagon were significantly elevated in CLP TPN rats, as
      were many inflammatory markers. Organ damage was evident as early as 12 h post
      CLP and blood cell kinetics indicated significantly depressed neutrophil and
      lymphocyte counts. CONCLUSIONS: Our results indicate that addition of TPN to CLP
      provides a clinically relevant animal model of critical illness with associated
      hyperglycemia that may provide utility for the testing of glucoregulatory and
      other therapeutic modalities.

PMID- 15501458
TI  - WP744 is a novel anthracycline with enhanced activity against neuroblastoma.
AB  - BACKGROUND: Doxorubicin (Dox) is one of the most useful chemotherapeutic agents
      for patients with advanced neuroblastoma (NB). A series of Dox analogs with bulky
      substitutions at the C-4' at amino-sugar have been designed to impair
      interactions between the drug and P-glycoprotein (P-gp), a multidrug drug
      resistance (MDR) transporter. Two analogs, WP744 and WP769, were selected and
      their biological properties were compared with Dox and the daunorubicin-based
      bisintercalator WP631. These novel Dox analogs may have antitumor activity beyond
      MDR evasion. MATERIALS AND METHODS: MTT assays were used to determine the potency
      of three structurally altered Dox analogs against a panel of NB cell lines with
      and without amplification of the MYCN oncogene. Flow cytometry (FCM) was used to
      analyze apoptosis and cell death and phenotype cell lines for surface expression
      of the MDR protein P-gp. RESULTS: The 4'-O-benzylated Dox analogs WP744 and WP769
      were 2 to 36 times more cytotoxic than Dox for the NB cell lines tested. The bis
      intercalator WP631, despite its significantly greater affinity for DNA (>10,000
      fold), was generally less potent against NB than Dox. In Tet21N cells, which
      conditionally express MYCN, greatly enhanced (nearly 6-fold) sensitivity to WP744
      killing was seen when this oncogene was induced, while enhanced sensitivity to
      Dox was more modest (2-fold) under MYCN-induced conditions. Treatment with WP744
      also resulted in enhanced apoptosis. Apoptosis, but not cell death, in response
      to either WP744 or Dox was inhibited by caspase inhibition, suggesting that cell
      death was not completely dependent upon apoptosis. P-gp expression was detectable
      on five NB cell lines. WP744 was more cytotoxic than Dox against both P-gp+ and P
      gp- cells. CONCLUSIONS: These findings demonstrate that 4'-O-benzylation of the
      anthracycline molecule significantly enhances potency against NB independent of
      MYCN status, caspase activation, and MDR phenotype. However, WP744 demonstrated a
      unique synergy with MYCN for cell killing when this oncogene was specifically
      induced. WP744 may be more useful than conventional agents for the treatment of
      tumor clones that harbor defects in apoptotic pathways, in those with MYCN
      amplification, and in those with drug-resistant tumors.

PMID- 15501459
TI  - Evolution of ischemic tissue injury in a random pattern flap: a new mouse model
      using intravital microscopy.
AB  - BACKGROUND: Dissection of random pattern flaps may cause microcirculatory
      dysfunction and ischemia, which jeopardize wound healing due to impaired tissue
      viability. The aim of this study was to develop an in vivo model that enables
      continuous monitoring of the interplay between microcirculatory dysfunction,
      ischemia, and tissue injury by intravital microscopy. MATERIALS AND METHODS: A
      laterally based random pattern skin flap (15 x 11 mm) including the panniculus
      carnosus was raised in the back of mice and fixed into a dorsal skinfold chamber
      (n = 10). Arteriolar blood flow, functional capillary density, number of
      apoptotic cells, and area of tissue necrosis were analyzed by intravital
      fluorescence microscopy in the proximal, middle, and distal part of the flap at
      day 1, 3, 5, and 7 after surgery. Chamber preparations without flap harvesting
      served as controls (n = 6). RESULTS: At day 1, the distal part of the flap showed
      a decreased arteriolar blood flow (266 +/- 124 pl/s versus controls: 1418 +/- 351
      pl/s; P < 0.05), which resulted in severe alteration of functional capillary
      density (43 +/- 11 cm/cm2 versus 270 +/- 7 cm/cm2; P < 0.001). The impaired
      microcirculation was associated with apoptotic cell death (277 +/- 50 cells/mm2
      versus 50 +/- 5 cells/mm2; P < 0.05). Microcirculatory dysfunction persisted over
      7 days, and, finally, resulted in 49 +/- 3% flap necrosis. CONCLUSIONS: This new
      model enables repetitive and simultaneous in vivo microscopic evaluation of
      microvascular hypoperfusion, apoptosis, and tissue necrosis in a random pattern
      flap. By the use of gene-targeted mice, it bears great potential to analyze
      distinct mechanisms of flap failure. It further represents an ideal tool to study
      novel protective strategies, including induction of angiogenesis, heat shock
      proteins, and HIF-1alpha.

PMID- 15501460
TI  - Interleukin-10 attenuates the response to vascular injury.
AB  - BACKGROUND: The inflammatory response to vascular injury is characterized by
      expression of cytokines, growth factors, and chemokines that conspire to promote
      vessel remodeling and intimal hyperplasia (IH). Interleukin-10 (IL-10) is a
      multifunctional cytokine that has several anti-inflammatory properties in vitro.
      Few studies have evaluated the effects of IL-10 in experimental atherosclerosis.
      The purpose of the present study was to determine the influence of IL-10 on
      vascular inflammation and IH following mechanical injury. METHODS: Wire carotid
      injury was performed in wild-type (WT) mice with and without IL-10 treatment.
      Immunohistochemistry, PCR, and ELISA assays were used to examine vessel
      production of basic fibroblast growth factor (bFGF), monocyte chemotactic protein
      1 (MCP-1), and nuclear factor kappa B (NFkappaB). Vessels were morphometrically
      analyzed for IH. RESULTS: Carotid injury induced early expression of MCP-1 and
      bFGF that was abrogated in mice treated with IL-10. Similarly, injury-induced
      expression of NFkappaB message and protein was attenuated in mice receiving
      exogenous IL-10. Compared to untreated mice, IL-10 markedly decreased levels of
      IH. Interestingly, carotid injury in IL-10-deficient mice resulted in an
      augmented IH response compared to injured WT mice. CONCLUSIONS: In an in vivo
      model of direct vascular injury, IL-10 decreased expression of the pro
      inflammatory transcription factor, NFkappaB, and the mitogenic chemokine and
      growth factor, MCP-1 and bFGF, respectively. These observations were associated
      with IL-10-induced attenuation of IH. Furthermore, endogenous IL-10 appeared to
      suppress the injury response. In conclusion, exogenously delivered IL-10 may
      represent a clinically relevant anti-inflammatory strategy for post-injury
      intimal hyperplasia.

PMID- 15501461
TI  - A report card on outcomes for surgically treated gastrointestinal cancers: are we
      improving?
AB  - INTRODUCTION: Longitudinal analyses of cancer registries provide an opportunity
      for population-based explanations of epidemiology and survival-related outcomes.
      This study used two population-based data sets to report on nine surgery-related
      cancers over the past three decades. MATERIALS AND METHODS: Using the SEER cancer
      database (1973-1999), all patients (>18 years old) with adenocarcinoma of
      esophagus, gastric, biliary system, pancreas, small bowel, colon, rectum;
      esophageal squamous cell carcinoma (ESC), or hepatocellular (HCC) carcinoma (n =
      379,640) were analyzed. Changes in incidence rates, stage at diagnosis, and 5
      year cancer and stage-specific survivals were determined. A separate database,
      the California inpatient database (1990-2000), was concurrently used to evaluate
      inpatient mortality after surgical resection (n = 34,057). RESULTS: Incidence
      rates increased for three cancers (esophageal, HCC, small bowel); decreased for
      three (rectal, gastric, ESC); and stayed constant for three (biliary, pancreatic,
      colon). More patients presented with local/regional disease in the 1990s versus
      1970s for eight tumors (except small bowel, P < 0.05). Five-year overall survival
      improved for all but small bowel (P < 0.05); and local stage survival was
      improved for all except small bowel and biliary (P < 0.05). Finally, inpatient
      mortality rates improved significantly for liver, esophageal, pancreatic, and
      gastric resections (P < 0.05) over the past decade. CONCLUSIONS: For these nine
      surgically treated cancers, we are detecting disease at earlier and therefore
      more treatable stages, and surgical care and outcomes also appear to have
      improved. Continued reexamination of longitudinal trends of surgically relevant
      outcomes is important for future improvement of surgical care.

PMID- 15501462
TI  - Long-term outcomes of clavicular pseudoarthrosis therapy.
AB  - BACKGROUND: Clavicular pseudoarthrosis is a rare condition, the management of
      which should not be underestimated because it requires re-operations and causes
      serious morbidity or even a lifelong handicap. PATIENTS AND METHODS: We reviewed
      a series of 13 patients with non-union of a clavicular fracture who underwent a
      surgical treatment from the year 1993 to 2002. Twelve fractures were a result of
      trauma and one was a result of osteomyelitis. Twelve non-unions were located in
      the middle third of the clavicle, while only one was in the lateral third. Seven
      non-unions were atrophic and six were hypertrophic. The average age of patients
      was 33 years (range: 14-52 years). Average post-operative follow-up time was 4.7
      years (range: 1-11 years). In the study, we used intramedullar osteosynthesis
      such as Kirschner wire, different kinds of plates and screws, followed by
      autogeneous or heterogeneous bone grafting. Constant scoring system was used to
      evaluate mobility and strength of the upper extremity. RESULTS AND CONCLUSION: A
      single operation was adequate in seven cases; two operations were adequate in
      four cases and three operations were adequate in one case. Fractures healed
      properly in 11 cases, but in some cases mild-to-moderate symptoms still persisted
      post-operatively. The results of 13 patients who underwent various surgical
      procedures show that a reconstruction plate should be the first choice of
      osteosynthesis, followed by a dynamic-compression plate, and a semitubular plate
      should be the last choice. To conclude, with this kind of treatment of clavicular
      pseudoarthrosis, we achieved a high degree of patient satisfaction, as well as
      objective improvements in status reports.

PMID- 15501463
TI  - The role of Osteopontin in tumor metastasis.
AB  - Osteopontin (OPN) is a glyco-phosphoprotein that is expressed and secreted by
      numerous human cancers. OPN functions in cell adhesion, chemotaxis, macrophage
      directed interleukin-10 (IL-10) suppression, stress-dependent angiogenesis,
      prevention of apoptosis, and anchorage-independent growth of tumor cells by
      regulating cell-matrix interactions and cellular signaling through binding with
      integrin and CD44 receptors. While constitutive expression of OPN exists in
      several cell types, induced expression has been detected in T-lymphocytes,
      epidermal cells, bone cells, macrophages, and tumor cells in remodeling processes
      such as inflammation, ischemia-reperfusion, bone resorption, and tumor
      progression. Recently, substantial evidence has linked OPN with the regulation of
      metastatic spread by tumor cells. However, the molecular mechanisms that define
      the role of OPN in tumor metastasis are incompletely understood. Transcriptional
      regulators that contribute to the induction of OPN expression have received
      significant attention as potential modulators of the OPN-mediated metastatic
      phenotype. The following review will discuss the molecular structure of OPN, the
      evidence for its functional role in tumor cell metastasis, the downstream signals
      that activate invasive mechanisms, and the recent reports concerning regulation
      of OPN transcription.

PMID- 15501464
TI  - How B cells and dendritic cells may cooperate in antigen purification.
AB  - The specificity of the immunological responses is achieved through the
      cooperation of three classes of cells: B and T lymphocytes, and dendritic cells
      (DCs). A critical, intensely studied interaction is that between DCs and T cells,
      during which the DC presents MHC-bound antigenic fragments to the T cell receptor
      (TCR). There has been recent excitement about the possibility of increasing the
      signal-to-noise ratio in the detection of cognate antigen-TCR couples, by the use
      of kinetic proofreading mechanisms. We examine here the signal-to-noise problem
      in a broader perspective, and in particular, address the question of possible
      "antigen purification" mechanisms, prior to their presentation to the T cells.
      Ways in which the DCs might concentrate, purify and preserve their load of
      captured antigens are considered: (i) If antigens can be transferred from one DC
      to another, in such a way that the richer a DC in antigen, the more it captures
      antigens from other DCs, the antigens may end up concentrated in a small subset
      of DCs, (ii) antigen purification may be achieved through recycling interactions
      between DCs and B cells. A DC would transmit to a B cell antigen mixtures, and
      the DC would recapture only the antigens which can bind to the B cell's
      antibodies and (iii) dendrites, when they are present, may play an essential role
      in recapturing the antigens that were used in interactions of DCs with T cells, B
      cells, or other DCs, thereby reducing antigen losses. More generally, we provide
      a personal interpretation of cell-to-cell antigen transfers, in terms of a
      strategy in which there is a progressive emergence, through multiple
      interactions, of subsets of cells of each type better and better prepared for the
      subsequent rounds of interactions.

PMID- 15501465
TI  - The relation between Hill's equation and individual muscle properties.
AB  - In this paper we deal with movement-independent individual muscle properties
      derived from Hill's equation. Relations between these properties are found by
      theoretical considerations. We define a dimensionless quantity that turns out to
      play a major role in characterizing individual muscle properties, and we analyse
      normalization and symmetry behaviour of the parameters in Hill's equation. This
      leads to a systematic, transparent, and useful overview of mathematical relations
      involving muscle parameters. We examine the experimentally determined parameters
      of 62 subjects to find additional empirical relations between the muscle
      properties described by the parameters of Hill's equation. In the light of the
      theoretical end empirical results we investigate the connections between maximum
      efficiency, endurance, and fibre composition.

PMID- 15501466
TI  - A general solution for optimal egg size during external fertilization, extended
      scope for intermediate optimal egg size and the introduction of Don Ottavio
      'tango'.
AB  - Egg sizes of marine invertebrates vary greatly, both within and between species.
      Among the proposed causes of this are a trade-off between egg size, egg number
      and survival probability of offspring, and a selection pressure exerted by sperm
      limitation during external fertilization. Although larger eggs are indeed a
      larger target for sperm, producing larger eggs also implies making fewer of them.
      There has been discussion about whether sperm limitation can (theoretically) and
      does (in nature) select for larger egg size than under ad libitum sperm. In one
      specific model, based on a particular fertilization kinetics model and an
      empirically derived mortality function, the theoretical possibility of a negative
      shift in optimal egg size with sperm concentration was demonstrated. Here we
      present a generalized analytical model to explore the effects of survival and
      fertilization probabilities on optimal egg size. It is demonstrated that
      incorporating fertilization kinetics greatly increases the scope for intermediate
      optimal egg size, as opposed to eggs of minimal or maximal size. Second, we
      present a general analytical qualitative solution to the question whether optimal
      egg size depends on sperm concentration. It is shown that, under the condition
      that an intermediate optimal egg size exists, this qualitative outcome of the
      model (positive, negative or no relation between optimal egg size and sperm
      limitation) depends on the structure of the fertilization kinetics part of the
      model. Finally, we evaluate fertilization kinetics models with respect to the
      general solution, using two previously published kinetics models ('Don Giovanni'
      and 'Don Ottavio') and a novel alteration of one of them in which sperm
      concentration covaries with egg concentration (Don Ottavio 'tango'). For all
      three models the relationship between optimal egg size and sperm concentration is
      shown to be always negative. This paper thus shows how biologically realistic
      relationships between egg size on the one hand and survival and fertilization
      probability on the other hand predict optimal egg size to be intermediate, and
      that this optimum is in general expected to increase when sperm become more
      limiting.

PMID- 15501467
TI  - Infection dynamics of different Wolbachia-types within one host population.
AB  - Wolbachia are widespread intracellular symbionts of arthropods which are known to
      cause several reproductive manipulations in their hosts, the commonest of which
      being cytoplasmic incompatibility (CI), male killing (MK), and the induction of
      parthenogenesis (PI). Strains of endosymbionts inducing one of these effects can
      be referred to as 'Wolbachia-types'. Here, we try to ascertain whether two of
      these Wolbachia-types can stably coexist within one population. We investigate
      this question by means of two discrete-time mathematical models which describe
      the dynamics of an infection of a host population with either CI- and MK- or CI-
      and PI-Wolbachia. We derive analytical solutions for two special cases of each
      model showing that stable coexistence of the respective Wolbachia-types is not
      possible if no doubly infected individuals occur within the population and that
      stable coexistence is possible when doubly infected hosts do exist and
      transmission of the endosymbionts is perfect. Moreover, we show that a population
      infected with either CI- or MK-Wolbachia at equilibrium can resist invasion of
      the respective other Wolbachia-type as a single infection. In contrast, a
      population infected with CI-Wolbachia can be invaded by PI-Wolbachia as a single
      infection with the CI-Wolbachia going extinct. Computer simulations confirmed
      these findings for the general models. We discuss our results with respect to the
      prevalence of the Wolbachia-types considered here and the emergence of PI- from
      CI-Wolbachia.

PMID- 15501468
TI  - Identifying control mechanisms of granuloma formation during M. tuberculosis
      infection using an agent-based model.
AB  - Infection with Mycobacterium tuberculosis is a major world health problem. An
      estimated 2 billion people are presently infected and the disease causes
      approximately 3 million deaths per year. After bacteria are inhaled into the
      lung, a complex immune response is triggered leading to the formation of
      multicellular structures termed granulomas. It is believed that the collection of
      host granulomas either contain bacteria resulting in a latent infection or are
      unable to do so, leading to active disease. Thus, understanding granuloma
      formation and function is essential for improving both diagnosis and treatment of
      tuberculosis. Granuloma formation is a complex spatio-temporal system involving
      interactions of bacteria, specific immune cells, including macrophages, CD4+ and
      CD8+ T cells, as well as immune effectors such as chemokine and cytokines. To
      study this complex dynamical system we have developed an agent-based model of
      granuloma formation in the lung. This model combines continuous representations
      of chemokines with discrete agent representations of macrophages and T cells in a
      cellular automata-like environment. Our results indicate that key host elements
      involved in granuloma formation are chemokine diffusion, prevention of macrophage
      overcrowding within the granuloma, arrival time, location and number of T cells
      within the granuloma, and an overall host ability to activate macrophages.
      Interestingly, a key bacterial factor is its intracellular growth rate, whereby
      slow growth actually facilitates survival.

PMID- 15501469
TI  - Renyi continuous entropy of DNA sequences.
AB  - Entropy measures of DNA sequences estimate their randomness or, inversely, their
      repeatability. L-block Shannon discrete entropy accounts for the empirical
      distribution of all length-L words and has convergence problems for finite
      sequences. A new entropy measure that extends Shannon's formalism is proposed.
      Renyi's quadratic entropy calculated with Parzen window density estimation method
      applied to CGR/USM continuous maps of DNA sequences constitute a novel technique
      to evaluate sequence global randomness without some of the former method
      drawbacks. The asymptotic behaviour of this new measure was analytically deduced
      and the calculation of entropies for several synthetic and experimental
      biological sequences was performed. The results obtained were compared with the
      distributions of the null model of randomness obtained by simulation. The
      biological sequences have shown a different p-value according to the kernel
      resolution of Parzen's method, which might indicate an unknown level of
      organization of their patterns. This new technique can be very useful in the
      study of DNA sequence complexity and provide additional tools for DNA entropy
      estimation. The main MATLAB applications developed and additional material are
      available at the webpage . Specialized functions can be obtained from the
      authors.

PMID- 15501470
TI  - The joint evolution of defence and inducibility against natural enemies.
AB  - We develop and analyse a model of inducible defence where two traits--defence and
      its inducibility--jointly evolve. Inducibility reduces costs of defence in the
      absence of enemies thereby permitting higher defence levels when attacked. If the
      cost of inducibility is low, then inducibility and defence may reinforce one
      another, resulting in a runaway leading to a highly inducible and highly
      effective defence. When inducibility is more costly, a new joint-equilibrium in
      defence/inducibility emerges displaying intermediate levels of both traits, and
      the prior 'run-away' scenario (high defence, high inducibility) may disappear. In
      contrast to the cost of inducibility, the cost of defence has mixed effects. An
      increase in costs of defence generally diminishes the level of both defence and
      inducibility at the intermediate locally stable equilibrium, but can favour the
      existence of the 'run-away' scenario of high defence-high inducibility. The enemy
      encounter-rate also has mixed effects. At high encounter rates an increase in
      encounters can lead to a higher/maximal defence and a lower level of inducibility
      (defence being almost always useful), but at low rates, an increase in encounters
      can lead to both higher defence and higher inducibility. We finally consider
      potential enemy responses to defensive change, and illustrate that herd immunity
      (reduction of encounter rates due to population-level defence) can affect both
      individual defence and induction that can be, depending on conditions, increased
      or decreased.

PMID- 15501471
TI  - Unifying and interpreting the spectral wavenumber content of EEGs, ECoGs, and
      ERPs.
AB  - A biological model of corticothalamic dynamics is used to investigate the spatial
      power spectrum (wavenumber spectrum) of electrical activity in the brain. The
      model provides a single framework for unifying different aspects of activity.
      Comparisons of the predicted spectra with published electrocorticographic,
      electroencephalographic, and evoked response potential data enable physiology and
      anatomy to be inferred, producing results which are complementary to those
      obtained from comparisons in the frequency domain; the inferred quantities are
      consistent with, and complementary to, direct physiological and anatomical
      measurements. We also use the model to quantify the interdependence of the
      wavenumber and frequency domains, and deduce that further experiments that cover
      large wavenumber and frequency ranges simultaneously would greatly increase our
      knowledge of brain function. We conclude that both the frequency and wavenumber
      domains should be studied in order to build the fullest picture of brain
      dynamics: the two domains are both complementary and interdependent.

PMID- 15501472
TI  - Estimation of neurophysiological parameters from the waking EEG using a
      biophysical model of brain dynamics.
AB  - This paper presents the results from using electroencephalographic (EEG) data to
      estimate the values of key neurophysiological parameters using a detailed
      biophysical model of brain activity. The model incorporates spatial and temporal
      aspects of cortical function including axonal transmission delays, synapto
      dendritic rates, range-dependent connectivities, excitatory and inhibitory neural
      populations, and intrathalamic, intracortical, corticocortical and
      corticothalamic pathways. Parameter estimates were obtained by fitting the
      model's theoretical spectrum to EEG spectra from each of 100 healthy human
      subjects. Statistical analysis was used to infer significant parameter variations
      occurring between eyes-closed and eyes-open states, and a correlation matrix was
      used to investigate links between the parameter variations and traditional
      measures of quantitative EEG (qEEG). Accurate fits to all experimental spectra
      were observed, and both inter-subject and between-state variability were
      accounted for by the variance in the fitted biophysical parameters, which were in
      turn consistent with known independent experimental and theoretical estimates.
      These values thus provide physiological information regarding the state.
      transitions (eyes-closed vs. eyes-open) and phenomena including cortical idling
      and alpha desynchronization. The parameters are also consistent with traditional
      qEEG, but are more informative, since they provide links to underlying
      physiological processes. To our knowledge, this is the first study where a
      detailed biophysical model of the brain is used to estimate neurophysiological
      parameters underlying the transitions in a broad range (0.25-50 Hz) of EEG
      spectra obtained from a large set of human data.

PMID- 15501473
TI  - The curse of the pharaoh in space: free-living infectious stages and the
      evolution of virulence in spatially explicit populations.
AB  - The idea that parasites with long-lived infective stages may evolve higher
      virulence has received considerable attention. This idea is called 'the curse of
      the pharaoh' because of the hypothesis that the death of Lord Carnavon was caused
      by very long-lived propagules of a highly virulent infectious disease. Here, we
      examined the evolution of diseases that transmit via free-living stages in a
      spatial context. We show that, if virulence evolves independently of
      transmission, long-lived infective stages can select for higher virulence. There
      is always the evolution of a finite transmission rate, which becomes higher when
      the infective stages are shorter lived. When a trade-off occurs between
      transmission and virulence, we show that there is no evidence for the curse of
      the pharaoh. Indeed, higher transmission and therefore virulence may be selected
      for by shorter rather than long-lived infective stages.

PMID- 15501474
TI  - Modeling the synchronization of yeast respiratory oscillations.
AB  - The budding yeast Saccharomyces cerevisiae exhibits autonomous oscillations when
      grown aerobically in continuous culture with ethanol as the primary carbon
      source. A single cell model that includes the sulfate assimilation and ethanol
      degradation pathways recently has been developed to study these respiratory
      oscillations. We utilize an extended version of this single cell model to
      construct large cell ensembles for investigation of a proposed synchronization
      mechanism involving hydrogen sulfide. Ensembles with as many as 10,000 cells are
      used to simulate population synchronization and to compute transient number
      distributions from asynchronous initial cell states. Random perturbations in
      intracellular kinetic parameters are introduced to study the synchronization of
      single cells with small variations in their unsynchronized oscillation periods.
      The cell population model is shown to be consistent with available experimental
      data and to provide insights into the regulatory mechanisms responsible for the
      synchronization of yeast metabolic oscillations.

PMID- 15501475
TI  - Alcohol effects on gamma-aminobutyric acid type A receptors: are extrasynaptic
      receptors the answer?
AB  - GABA(A) receptors have long been implicated in mediating at least part of the
      actions of ethanol in mammalian brain. However, until very recently, reports of
      the actions of EtOH on recombinant receptors have required very high doses of
      ethanol and animals lacking receptor subunits shown to be important for ethanol
      actions in vitro did not support the view that these subunits are crucial in
      ethanol actions. Recombinant alpha4beta3delta and alpha6beta3delta GABA(A)
      receptors are uniquely sensitive to ethanol, with a dose-response relationship
      mirroring the well known effects of alcohol consumption on the human brain.
      Receptors containing the delta subunit are thought to be located
      extrasynaptically and it will be important to determine if these extrasynaptic
      GABA(A) receptor subunit combinations mediate low dose alcohol effects in vivo.

PMID- 15501476
TI  - Incubation of rat aortic rings produces a specific reduction in agonist-evoked
      contraction: effect of age of donor.
AB  - We studied the effect of age on the response of aortic rings to injury produced
      by three days' incubation, and the mechanism of this response. Five-mm rings of
      the thoracic aorta isolated from Wistar rats were incubated or not in culture
      medium. Isometric contraction evoked by agonists (norepinephrine or serotonin) or
      high [K(+)](e) was determined in the presence and absence of endothelium.
      Experiments were repeated in the presence of propranolol (0.3 microM), polymixin
      B (36 microM), pyrrolidine dithiocarbamate (50 microM) or glutathione (3 mM).
      Inductible NO-synthase and cyclo-oxygenase-2 mRNA were determined by real-time
      PCR, and glutathione-related enzymes and catalase activity by spectrophotometry.
      Incubation reduced the isometric contraction evoked by agonists but not by high
      [K(+)](e). The reduction in agonist-evoked contraction was greater in rings from
      adult (norepinephrine Emax-80%) than in young (-40%) rats. The removal of the
      endothelium had no effect. The reduction in norepinephrine-evoked contraction was
      not due to endotoxin contamination, beta-adrenoceptor-mediated dilation or any
      change in ring structure (no fibrosis or edema). Inductible NO-synthase (but not
      cyclo-oxygenase-2) mRNA increased on incubation. N(G)-nitro-L-arginine methyl
      ester partially restored contractility in rings from adult animals, further
      addition of an anti-oxidant restored norepinephrine-evoked contraction. Catalase
      fell with age and glutathione reductase increased upon incubation in rings from
      young donors only. In conclusion, incubation of the aorta produces a specific
      reduction in agonist-evoked contraction that involves induction of smooth muscle
      cell oxidative stress and iNOS. The reaction is greater in rings from older
      animals.

PMID- 15501477
TI  - TGF-beta1 induces alveolar epithelial to mesenchymal transition in vitro.
AB  - The aim of this study was to investigate whether transforming growth factor-beta1
      (TGF-beta1) could induce alveolar epithelial to mesenchymal transition (EMT) in
      vitro. Alveolar epithelial cells (AECs) from SD rats were isolated by elastase
      cell dispersion and IgG panning. Expression of alpha-smooth muscle actin (alpha
      SMA) was assayed using Western blotting and immunostaining analysis.
      Morphological changes, the markers of epithelial cell (E-cadherin), and stress
      fiber by actin reorganization were detected by an indirect immunostaining. The
      contents of collagen I were determined by spectrophotometry. The levels of
      endogenous TGF-beta1 were measured with ELISA. Incubation of AECs with TGF-beta1
      (0.1 approximately 10 ng/mL) induced abundant expression of alpha-SMA protein,
      and alpha-SMA expression in AECs reached a plateau when TGF-beta1 was > 3 ng/mL.
      Furthermore, we found that TGF-beta1 (3 ng/mL) exposure of AECs induced an
      authentic EMT characterized by abundant expression of alpha-smooth muscle actin,
      transformation of myofibroblastic morphology, increased formation of stress fiber
      by actin reorganization, and loss of epithelial marker E-cadherin. Meanwhile,
      significant increase in the levels of collagen I from 32.0 +/- 6.6 mg/g in
      control to 98 +/- 10.8 mg/g in TGF-beta1-treated group was found over a 72 h
      incubation period. Moreover, following stimulated by TGF-beta1 (3 ng/mL), a
      marked and time-dependent increase in endogenous TGF-beta1 released from AECs was
      observed. At time points 72 h, TGF-beta1 release mounted to 3451 pg/ml, which was
      much enough to induce EMT in vitro. These results demonstrated that AECs, under
      stimulation of TGF-beta1, underwent a conversion process into myofibroblasts in
      vitro.

PMID- 15501478
TI  - Impact of warm ischemic time on microsomal P450 isoforms in a porcine model of
      therapeutic liver resection.
AB  - Human microsomes and hepatocytes obtained from non-transplantable livers of brain
      dead donors are very useful in predicting the in vivo metabolism of xenobiotics
      in humans. Fresh liver specimens obtained from therapeutic liver resection are
      also useful for research in cases where non-transplantable livers are not readily
      available. In the present study, the effect of warm ischemic duration, in the
      course of hepatic surgery, on the activities of liver cytochrome P450 (CYP)
      CYP1A, CYP2C, CYP2D, CYP2E1 and CYP3A were evaluated in a porcine model. Partial
      occlusion (portal vein and hepatic artery occlusion) decreased the activities of
      CYP2C, CYP2E and CYP3A, but not those of CYP1A and CYP2D. CYP3A, known to account
      for an average 30% of total P450 content in the human liver was the most
      susceptible to the warm ischemia. These results demonstrate that the activities
      of CYP isoforms, particularly those of CYP3A, are markedly affected by warm
      ischemia; it is, therefore, essential that care should be exercised when using
      microsomes prepared from surgically removed livers.

PMID- 15501479
TI  - AZT induces oxidative damage to cardiac mitochondria: protective effect of
      vitamins C and E.
AB  - AZT (zidovudine) is a potent inhibitor of HIV replication and a major
      antiretroviral drug used for AIDS treatment. A major limitation in the use of AZT
      is the occurrence of severe side effects. The aim of this work was to test
      whether AZT causes oxidative damage to heart mitochondria and whether this can be
      prevented by supranutritional doses of antioxidant vitamins. An experimental
      animal model was used in which mice were treated with AZT for 35 days (10
      mg/kg/day) in drinking water. Animals treated with antioxidant vitamins were fed
      the same diet as controls but supplemented with vitamins C (ascorbic acid, 10 g/
      kg diet) and E (alpha-dl-tocopherol, 0.6 g/kg diet) for 65 days before sacrifice.
      This resulted in a daily intake of 1250 mg/kg/day (vitamin C) and 75 mg/kg/day
      (vitamin E). Cardiac mitochondrial DNA (mtDNA) of mice treated with AZT had over
      120% more oxo-dG (8-oxo-7,8-dihydro-2'-deoxyguanosine, which is a biomarker of
      oxidative damage to DNA) in their mitochondrial DNA than untreated controls. AZT
      treatment also caused an increase in mitochondrial lipid peroxidation and an
      oxidation of mitochondrial glutathione. Dietary supplementation with
      supranutritional doses of the antioxidant vitamins C and E protected against
      these signs of mitochondrial oxidative stress. The oxidative effects of AZT are
      probably due to an increase in production of reactive oxygen species by
      mitochondria of AZT-treated animals, raising the possibility that oxidative
      stress may play an important role in the cardiotoxicity of AZT.

PMID- 15501480
TI  - The phosphatidylinositol/AKT/atypical PKC pathway is involved in the improved
      insulin sensitivity by DHEA in muscle and liver of rats in vivo.
AB  - DHEA improves insulin sensitivity and has anti-obesity effect in animal models
      and men. However, the molecular mechanisms by which DHEA improves insulin action
      have not been clearly understood. In the present study, we examined the protein
      levels and phosphorylation state of insulin receptor (IR), IRS-1 and IRS-2, the
      association between IRSs and PI3K and SHP2, the insulin-induced IRSs associated
      PI 3-kinase activities, and the phosphorylation status of AKT and atypical
      PKCzeta/lambda in the liver and the muscle of 6 month-old Wistar rats treated
      with DHEA. There was no change in IR, IRS-1 and IRS-2 protein levels in both
      tissues of treated rats analysed by immunoblotting. On the other hand, insulin
      induced IRS-1 tyrosine phosphorylation was increased in both tissues while IRS-2
      tyrosyl phosphorylation was increased in liver of DHEA treated group. The PI3
      kinase/AKT pathway was increased in the liver and the PI3K/atypical
      PKCzeta/lambda pathway was increased in the muscle of DHEA treated rats. These
      data indicate that these regulations of early steps of insulin action may play a
      role in the intracellular mechanism for the improved insulin sensitivity observed
      in this animal model.

PMID- 15501481
TI  - Irsogladine, an anti-ulcer drug, suppresses superoxide production by inhibiting
      phosphodiesterase type 4 in human neutrophils.
AB  - Neutrophil superoxide production is implicated in the pathogenesis of gastric
      mucosal damage induced by various ulcerative agents and Helicobacter pylori
      infection. We investigated here the effects of an anti-ulcer drug irsogladine [2,
      4-diamino-6-(2, 5-dichlorophenyl)-s-triazine maleate] on cAMP formation in
      isolated human neutrophils. The cAMP level in human neutrophils was elevated by a
      phosphodiesterase (PDE) type 4 selective inhibitor rolipram, but not by any
      inhibitors of PDE1, PDE2 and PDE3. Irsogladine also increased cAMP formation in a
      concentration-dependent manner in neutrophils. A non-selective PDE inhibitor 3
      isobutyl-1-methylxanthine (IBMX) alone significantly increased cAMP level,
      whereas irsogladine was unable to further increase cAMP level in the presence of
      IBMX. Irsogladine inhibited concentration-dependently the superoxide (O(2)(-))
      production induced by various stimuli including formyl-methionyl-leucyl
      phenylalanine, opsonized zymosan, guanosine 5'-[gamma-thio] triphosphate, A23187
      and phorbol 12-myristate 13-acetate. These effects of irsogladine were mimicked
      by rolipram, IBMX and dibutyryl cAMP. The inhibitory effects of irsogladine and
      rolipram on the O(2)(-) production were reversed by a protein kinase A inhibitor
      H-89. These results indicate that irsogladine inhibits the superoxide production
      in human neutrophils by the increase of cAMP content by PDE 4 inhibition, which
      in turn contributing to the anti-ulcer effects of irsogladine on gastric mucosal
      lesions associated with oxidative stress.

PMID- 15501482
TI  - Antigenotoxic properties of Cassia tea (Cassia tora L.): mechanism of action and
      the influence of roasting process.
AB  - Antigenotoxic properties and the possible mechanisms of water extracts from
      Cassia tora L. (WECT) treated with different degrees of roasting (unroasted and
      roasted at 150 and 250 degrees C) were evaluated by the Ames Salmonella/microsome
      test and the Comet assay. Results indicated that WECT, especially unroasted C.
      tora (WEUCT), markedly suppressed the mutagenicity of 2-amino-6
      methyldipyrido(1,2-a:3':2'-d)imidazole (Glu-P-1) and 3-amino-1,4-dimethyl-5H
      pyrido(4,3-b)indole (Trp-P-1). In the Comet assay performed on human lymphocytes,
      WECT exhibited significant protective effect on Trp-P-1-mediated DNA damage
      followed the order of unroasted (55%) > roasted at 150 degrees C (42% ) > roasted
      at 250 degrees C (29%). Pre-treatment of the lymphocytes with WEUCT resulted in
      30% repression of DNA damage. However, no significant effect on excision-repair
      system was found during DNA damage expression time in post-treatment scheme
      (p>0.05). WEUCT showed 84% scavenging effect on oxygen free radicals generated in
      the activation process of mutagen detected by electron paramagentic resonance
      system. Two possible mechanisms were considered: (1) neutralization the reactive
      intermediate of Trp-P-1; and (2) protecting cells directly as an antioxidant that
      scavenge the oxygen radicals from the activation process of mutagen. The
      individual anthraquinone content in extracts of C. tora was measured by HPLC.
      Three anthraquinones, chrysophanol, emodin and rhein, have been detected under
      experimental conditions. The anthraquinone content decreased with increased
      roasting temperature. Each of these anthraquinones demonstrated significant
      antigenotoxicity against Trp-P-1 in the Comet assay. In conclusion, our data
      suggest that the decrease in antigenotoxic potency of roasted C. tora was related
      to the reduction in their anthraquinones.

PMID- 15501485
TI  - Olfactory perception, communication, and the nose-to-brain pathway.
AB  - The present paper's aim is of to give an overview about the basic knowledge as
      well as actual topics of olfaction--with a special regard on behavior. We
      summarize different functions of the nose and the olfactory system in human
      physiology and psychology. We will first describe the functional anatomy of the
      olfactory system in man. Afterwards, the function of the olfactory system will be
      viewed from an evolutionary and phylogenetic perspective. We will further outline
      the main features of olfactory perception, and will show how olfactory perception
      is influenced by learning. Olfactory signals are relevant stimuli that affect
      communication. Consequently, the role of the olfactory system in social
      interaction and mood will be described and gender differences will be addressed.
      Finally, the function of the nose as an interface to the brain, including
      implications for pharmacology, will be discussed.

PMID- 15501483
TI  - The effect of a series of organic cations upon the plasmalemmal serotonin
      transporter, SERT.
AB  - The aim of this work was to test the effect of a series of organic cations upon
      the activity of the plasma membrane serotonin transporter (SERT). The experiments
      were performed using the JAR cell line that constitutively expresses high levels
      of SERT, and rat intestine, whose mucosal epithelial cells also express SERT.
      Initial rates of (3)H-serotonin ((3)H-5HT; 200 nM) uptake were not changed by
      some of the organic cations tested (guanidine, N-methylnicotinamide, choline,
      atenolol, caffeine and theophylline), but were slightly (15-30%) inhibited by
      some other organic cations, at the highest concentrations tested (thiamine (3
      mM), cimetidine (1 mM) and tetraethylammonium (3 mM)). On the other hand, some
      other organic cations reduced, in a concentration-dependent manner, uptake of
      (3)H-5HT by JAR cells (IC(50)s of 0.3, 1.3, 5.4, 89.3, 460 and 748 microM for
      quinidine, verapamil, propranolol, amiloride, nicotine and clonidine,
      respectively). Quinidine, clonidine and amiloride seem to be competitive
      inhibitors of (3)H-5HT uptake, whereas verapamil, nicotine and propranolol appear
      to be uncompetitive or non-competitive inhibitors. Moreover, quinidine, verapamil
      and propranolol trans-inhibited (3)H-5HT uptake, whereas clonidine, nicotine and
      amiloride were devoid of effect. Finally, these six organic cations were able to
      significantly increase the serosal-to-mucosal apparent permeability (P(app)) to
      (3)H-5HT of rat jejunum, ileum and colon. In conclusion, human and rat SERT
      mediated transport is inhibited by several distinct organic cations, some of
      which are therapeutic agents or drugs of abuse. Knowledge on which organic
      cations interfere with SERT-mediated transport of 5HT will have major
      implications in tissues where 5HT plays important physiological roles (eg.
      central nervous system, intestine and placenta).

PMID- 15501486
TI  - Recording of the human electro-olfactogram.
AB  - Electro-olfactograms (EOG) are electrical potentials of the olfactory epithelium
      that occur in response to olfactory stimulation. The EOG represents the sum of
      generator potentials of olfactory receptor neurons. While this response has been
      used extensively in animal research, there are only a handful of papers
      describing the properties of the human EOG. In addition to a discussion of
      methodological issues related to the EOG, this review summarizes the
      characteristics and uses of these recordings. Among other results, EOGs have been
      used to provide evidence for the dominant role of the central nervous system in
      olfactory desensitization, for the functional characterization of the olfactory
      epithelium, the specific topographical distribution of olfactory receptors, or
      the expression of olfactory receptor neurons in response to exposure to odorants,
      and the characterization of certain odorants as olfactory receptor antagonists.
      In conclusion, in combination with nasal endoscopy and air-dilution olfactometry,
      the EOG is a unique part of a large array of techniques used to provide a
      complete picture of the processing of olfactory information in humans.

PMID- 15501487
TI  - Are androgen steroids acting as pheromones in humans?
AB  - In animals, chemosensory communication is successfully used to transmit
      behaviourally relevant information, e.g. information about sexual status, danger
      and social organisation. In many instances pheromones might have evolved from
      hormone-like substances. Consequently, a large number of studies have been
      carried out in humans, in order to investigate possible pheromonal properties of
      androgen steroids. Besides discussing the production and perception of androgen
      steroids, it will primarily be questioned whether their perception can alter mood
      and behaviour in humans. Therefore, a study has been carried out to investigate
      whether local preferences can be altered through androstenone exposure. It is
      shown that heterosexual women and homosexual men prefer seats sprayed with
      androstenone. However, as this effect is positively correlated with the
      sensitivity to androstenone, the effect might be due to a general olfactory
      attraction of low androstenone concentrations. In regard to the conflicting
      results of studies on putative human pheromones, it will finally be discussed
      whether the perceptual context and the individual learning history of the
      perceiver contribute significantly to a successful communication of pheromonal
      information.

PMID- 15501488
TI  - Selective amnesic effects of oxytocin on human memory.
AB  - The neuropeptide oxytocin is essential for mammalian parturition and lactation.
      Recent animal studies suggest that oxytocin is also implicated in the central
      nervous control of behavior including learning and memory. There has been little
      investigation, however, of the impact of oxytocin on human memory. The purpose of
      this study was to investigate the effect of a single dose of intranasal oxytocin
      on implicit and explicit memory in humans. In a placebo-controlled, double-blind
      study, 38 healthy men were randomly assigned to receive intranasal oxytocin (24
      IU) or placebo 50 min before the study phase (incidental learning). Memory was
      measured using three different memory tests: an implicit perceptual test (word
      stem completion), an implicit conceptual test (category-cued semantic
      association), and an explicit test (cued recall). Due to the reproductive
      biological role of oxytocin and the impact of adequate environmental conditions
      for the stimulation of behavioral effects of oxytocin known from animal research,
      we used semantic word stimuli with reproduction-related vs. neutral meaning.
      Oxytocin significantly impaired recall performance as compared with placebo
      treatment irrespective of the meaning of words in the cued recall test. In the
      implicit conceptual test, characterized by a deepened information processing,
      compared with placebo, oxytocin significantly impaired only the overall
      generation of associated target words with reproduction relevant meaning, whereas
      no significant difference between oxytocin and placebo was obtained for neutral
      words. These findings concur with data from animal research suggesting that
      central oxytocin selectively influences memory performance depending on the kind
      of memory test used and, more importantly, the psychobiological relevance of
      stimuli.

PMID- 15501489
TI  - Repetitive intranasal administration of cholecystokinin potentiates its central
      nervous effects.
AB  - Functional evidence exists for a nose-brain pathway for the neuropeptide
      cholecystokinin-8 (CCK-8S). The transport mechanism, however, remains still
      unclear. Previous studies indicate a saturable dose-response curve on the
      magnitude of the late positive complex of the auditory event-related potential
      (AERP) with increasing doses of intranasally administered CCK-8S. Thus, the
      present study served to bypass this saturation by repeated lower dose intranasal
      administrations of CCK-8S. It was expected that this repetitive administration
      results in a nonsaturable dose-response effect on AERPs. AERPs reflecting
      cortical stimulus processing were recorded while subjects performed on an
      auditory attention task (oddball paradigm) four times (in intervals of 30 min)
      each following a separate 10-microg intranasal administration of CCK-8S or
      placebo. Compared with placebo, the repetitive intranasal administration of CCK
      8S linearly enhanced the late positive complex and its subcomponent slow wave.
      Blood plasma CCK-8S levels were not affected by intranasal CCK-8S. The results
      suggest that by using a repetitive intranasal administration of CCK-8S, a
      saturable mechanism for central nervous CCK-8S effects can be avoided.

PMID- 15501490
TI  - Insulin and the CNS: effects on food intake, memory, and endocrine parameters and
      the role of intranasal insulin administration in humans.
AB  - Insulin is mainly known for its peripheral effects on the metabolism of glucose,
      fats, and proteins. However, insulin also exerts important actions within the
      brain, and functions as a neuropeptide. The brain can thus be regarded as both an
      insulin-sensitive and a glucose-sensitive organ. Its neuroanatomical basis is the
      localization of insulin receptors, predominantly in the olfactory bulbs,
      hypothalamus, and hippocampus. Data obtained in animal experiments reveal an
      interesting insulin profile in the brain. Central insulin affects
      glucoregulation. As long as peripheral euglycemia is maintained, it was shown to
      reduce food intake and body weight and to improve learning and memory. Cognitive
      dysfunctions in dementia of the Alzheimer type (DAT) are associated with insulin
      deficiency within the brain, and memory improves in DAT patients when insulin
      levels increase. After describing these actions of insulin in the brain, we
      address here the transport of insulin into the brain. Insulin can either be
      transported from the periphery to the brain, or be administered directly into the
      brain. To reach insulin receptors directly, animals are typically administered
      insulin via the cerebral ventricles. For humans, the intranasal route is a
      practicable way to reach the brain while maintaining euglycemia. Additionally,
      the localization of insulin receptors in the olfactory bulb makes insulin
      interesting for the nose-to-brain pathway. Promising initial results have been
      reported with intranasally administered insulin corresponding to the diverse
      actions of insulin in the brain. Interestingly, initial data indicate that states
      of central insulin deficiencies (DAT and obesity) are accompanied by olfactory
      deviations. Thus, the nose-to-brain pathway deserves further attention.

PMID- 15501491
TI  - Manipulating central nervous mechanisms of food intake and body weight regulation
      by intranasal administration of neuropeptides in man.
AB  - Maintaining a stable body weight set-point is assumed to rely on a homeostatic
      central nervous system (CNS) regulation of body fat with the particular
      involvement of hypothalamic pathways. The peripheral adiposity signals insulin
      and leptin convey information on the amount of energy stored as body fat to the
      arcuate nucleus of the hypothalamus, where anabolic/orexigenic and
      catabolic/anorexigenic pathways interact to regulate food intake and energy
      expenditure. One of the most prominent orexigenic messengers is neuropeptide Y
      (NPY), whereas melanocortins, including alpha-melanocyte-stimulating hormone
      (alpha-MSH), are essential for inducing anorexigenic effects. The melanocortin
      receptor 4 (MC4-R) plays the most important role in mediating catabolic effects
      of alpha-MSH. In this review, we present a series of own studies on NPY, insulin
      and MSH/ACTH4-10, an MC4-R agonist. The studies were all based on the intranasal
      route of administration which enables a direct access of the peptides to
      hypothalamic functions. NPY acutely attenuated electrocortical signs of meal
      related satiety. Prolonged intranasal administration of insulin as well as of MSH
      induced weight loss in healthy human subjects. However, overweight subjects did
      not lose body fat after MSH administration. The results corroborate in humans the
      significance of all three messengers for the central nervous regulation of
      adiposity and might contribute to the future development of medical strategies
      against body-weight-related disorders.

PMID- 15501492
TI  - Intraperitoneal leptin modifies macronutrient choice in self-selecting rats.
AB  - This study aimed to evaluate the consequences on food intake and body weight (BW)
      of leptin administration in rats receiving a choice between the three
      macronutrients. Two studies were performed: during the first, rats received an
      acute intraperitoneal (IP) leptin administration (1 mg/kg) twice (at 8 and 14
      weeks of age), at the beginning of the nocturnal cycle, while during the second,
      they received a chronic leptin infusion (osmotic minipump, 7 days). The total 24
      h food intake after acute leptin injections was reduced by 14% and 17%,
      respectively. Body weight gain (BWG) after leptin injections was about half that
      seen on control days. Chronic leptin infusion reduced total intake, affecting
      mainly protein (P). Fat intake increased slightly since day 2 and became
      significant on the fourth day. After the leptin infusion, carbohydrate (CHO)
      eaters (>35% carbohydrate/total energy) significantly reduced the carbohydrate
      proportion in their total energy intake. There was no difference concerning
      macronutrient selection by fat eaters (Hfat). Leptin infusion reduced the number
      of mixed meals on the first day. In addition, the thermogenesis of brown adipose
      tissue (BAT) was higher in leptin than in control (C) rats. Consequently, leptin
      injections reduced food intake and BWG and increased thermogenesis, thus acting
      on the two terms of the energy balance. Moreover, leptin has different effects on
      macronutrient preferences, dependent upon age (tests 1 and 2) and the type (acute
      or chronic) of injection. High leptinemia level related to age or to minipump
      infusion lead to leptin resistance as found in old or obese subjects. It could
      explain our results.

PMID- 15501493
TI  - Social interactions differentially affect reproductive and immune responses of
      Siberian hamsters.
AB  - Social interactions can have pronounced effects on reproductive physiology and
      behavior in a wide range of species. Much less is known about the effects of
      social interactions on immunity. The goal of the present study was to test the
      effects of social interactions on both reproductive and immune responses in
      Siberian hamsters (Phodopus sungorus). Male and female hamsters were housed
      alone, in same-sex pairs or in mixed-sex pairs for 4 weeks. Animals were then
      immunized with the antigen keyhole limpet hemocyanin (KLH) and blood samples were
      drawn 5 days postinoculation. Reproductive tissue masses, testosterone, 17beta
      estradiol and cortisol concentrations were measured and immunity was assessed by
      measuring serum anti-KLH IgM, and mitogen-stimulated splenocyte proliferation.
      Male hamsters housed with a female had increased testosterone and anti-KLH IgM
      and elevated splenocyte proliferation compared with males housed alone. Female
      hamsters housed in same-sex pairs had increased serum IgM compared with females
      housed with males. Cortisol was elevated in both sexes housed with male
      conspecifics compared with the other experimental groups. Serum estradiol
      concentrations did not differ among females in any group. Collectively, the
      results of the present study suggest that social interactions can alter
      reproductive responses, but that these changes appear unrelated to changes in
      immunity. In contrast, the presence of a male conspecific elicits social-stress
      induced elevations in serum cortsiol in both males and females, which is
      generally immunosuppressive. These data support the notion of social-stress
      induced suppression of immune humoral and cell-mediated immune responses.

PMID- 15501494
TI  - The role of alpha-amylase in the perception of oral texture and flavour in
      custards.
AB  - The role of salivary alpha-amylase in odour, flavour, and oral texture sensations
      was investigated in two studies in which the activity of salivary amylase present
      in the mouth of human subjects was either increased by presenting custards with
      added alpha-amylase or decreased by presenting custards with added acarbose, an
      amylase inhibitor. For starch-based vanilla custard desserts, amylase resulted in
      increased melting and decreased thickness sensations, whereas acarbose had the
      opposite effect, i.e., decreased melting and increased thickness. Other affected
      attributes included creamy mouth feel, creamy after feel, and fatty after feel.
      Creaminess, which is considered to be a highly desirable food quality, decreased
      by as much as 25% with added amylase and increased by as much as 59% with added
      acarbose. Neither additional amylase nor acarbose affected sensations for a
      nonstarch-based carboxy methylcellulose (CMC) vanilla custard dessert. This
      indicates that the effects of amylase on viscosity-related sensations of starch
      based custards, such as perceived melting and thickness, are caused by amylase
      induced breakdown of starch. Partial Least Square (PLS) analysis indicated that
      the effects of amylase and acarbose on perceived creaminess are not only driven
      by their effects on perceived melting and thickness, but also by their effects on
      perceived flavour.

PMID- 15501495
TI  - Conditioned food aversion elicited by the temperature of drinking water as a
      conditioned stimulus in rats.
AB  - It is known that taste can act as a conditioned stimulus (CS) for conditioned
      food aversion. In the present study, in order to examine whether or not the
      temperature of drinking water can be a CS, we conducted behavioral experiments in
      Wistar rats. The following results were obtained: (1) The rats subjected to
      aversive conditioning to 5 or 40 degrees C distilled water could learn to avoid
      these CSs, but they did not avoid any taste stimuli. (2) The rats subjected to
      aversive conditioning to 5 or 40 degrees C 0.1 M sucrose developed a generalized
      avoidance to sucrose at any temperature. (3) When rats familiarized to 25 degrees
      C 5 mM saccharin-Na (Sacc) were subjected to aversive conditioning to 5 or 40
      degrees C Sacc, they avoided the respective CS, but they did not generalize it to
      any other stimuli even if having the same temperature as the CS. (4) The rats
      which had undergone transection of the taste nerves (chorda tympani and
      glossopharyngeal nerves) could acquire the conditioned response to the
      temperature of the CS. These results suggest that rats can be conditioned to
      temperature aversion and that the taste nerves are not needed in the formation of
      this conditioning.

PMID- 15501496
TI  - The effects of aromatase inhibition on testosterone-dependent conditioned
      rhythmic cloacal sphincter movements in male Japanese quail.
AB  - Male Japanese quail produce a foam that, along with semen, is transferred to the
      quail hen during copulation. This foam has been reported to increase fertility,
      prolong sperm motility, and enhance sperm competition. Action of the cloacal
      sphincter muscles in response to visual exposure to a female produces the foam.
      The rhythmic cloacal sphincter movements (RCSM) responsible for foam production
      in male quail is elicited by a conditioned stimulus (CS) previously paired with
      access to a quail hen. These conditioned RCSM are testosterone-dependent. The
      present experiment was conducted to explore whether, as is the case with most
      other testosterone-dependent male sexual behaviors in the quail, conditioned RCSM
      are mediated by the aromatization of testosterone. Castrated, testosterone
      treated male quail were presented with paired presentations of an arbitrary focal
      CS and visual access to a female. Once conditioned RCSM had developed, subjects
      received twice daily injections of the aromatase inhibitor Vorozole (R083842)
      during a series of extinction test presentations of the CS. Injections of
      Vorozole significantly decreased the number of RCSMs elicited by a sexual CS.
      This decrease was specific to sexual RCSM; cloacal sphincter movements that
      occurred following defecation were not affected by Vorozole. Conditioned sexual
      RCSM are therefore mediated by the aromatization of testosterone, most likely due
      to effects on central aromatase activity related to sexual motivation.

PMID- 15501497
TI  - Astronomical and meteorological parameters and rest-activity rhythm in the spider
      monkey Ateles geoffroyi.
AB  - All animals including primates show regular variations in their behavioural
      activities and physiological functions. In numerous species diel, ultradian,
      infradian, annual and/or lunar rhythms have been established; however, the use of
      the focal sampling method does not provide information on hour-to-hour nor day-to
      day variations. In behavioural field studies dealing with primate activity
      rhythms and their modulation by environmental variables the possible dual,
      synchronizing and/or masking effect of these variables is often ignored. In the
      present study, we analyze the relation between astronomical and meteorological
      parameters and various parameters of the rest-activity rhythm in Ateles
      geoffroyi, a species scarcely investigated with respect to biological rhythms.
      These Ateles were kept under semi-natural conditions, exposed to natural light,
      temperature and humidity cycles, and sky state. Motor activity was recorded with
      actiwatch accelerometers during 180 days (5-min intervals), starting from the
      autumn equinox. RESULTS: Ateles is active throughout the day, rests during the
      night and presents bimodal activity. Activity time, onset and end of activity as
      well as the times of their two activity peaks were significantly correlated with
      duration of the solar day and sunrise or sunset time. The behavioural parameters
      also correlated with ambient temperature. Climate factors and sky-state
      significantly influenced the duration and times of onset and end of activity. Our
      findings identified a clear modulation of the rest-activity pattern by
      astronomical variables serving as Zeitgebers, such as the natural light-dark
      cycle, and by masking effects of meteorological factors (temperature, weather and
      cloudiness), as well as of artificial variables introduced by the interaction
      with man.

PMID- 15501498
TI  - Sex differences in Mongolian gerbils in four tests of anxiety.
AB  - Animal models or test paradigms for predominantly female disorders, such as
      anxiety, often use only male animals, with little or no investigation of sex
      differences. Thus, this study was conducted to compare the behaviour of males and
      females in four widely used tests of anxiety. The behaviour of male and female
      Mongolian gerbils was assessed in the elevated plus maze (EPM), black-white box
      (BWB), open-field and social interaction tests. In the elevated plus maze,
      females spent proportionally less time in the centre square and greater time in
      the closed arms compared with males. In the black-white box, they showed
      significantly greater entries into the black compartment, whilst in the open
      field, females spent less time sniffing the arena compared with males. Thus, in
      these three models, there are no conclusive sex differences in anxiety-like
      behaviour. However, in the social interaction test, females showed more
      exploratory/cage-orientated behaviour and less active social and aggressive
      behaviour. In addition, females terminated social contact more frequently. These
      results can be interpreted as true sex differences, as behaviour in the open
      field and social interaction tests did not differ across the oestrous cycle. In
      conclusion, the results show that sex differences in anxiety-like behaviour in
      gerbils are best detected using the social interaction test, which suggests that
      females show a more anxious profile. It also further highlights the need for sex
      differences to be investigated in tests of anxiety.

PMID- 15501499
TI  - Increased locomotor response to amphetamine, but not other psychostimulants, in
      adult mice submitted to a low-protein diet.
AB  - Protein malnutrition results in a variety of brain dysfunctions, ultimately
      affecting cognitive functions. The effects of protein malnutrition in brain
      response to psychostimulants have been less studied in adult animals. We
      therefore aimed to study the response to psychoactive drugs on the locomotor
      activity (a behavior paradigm) of adult protein malnourished mice. Two-month-old
      mice were divided in two groups: (a) low-protein group (LP), which received 6% of
      protein diet, and (b) a control group that received a 25% of protein diet. After
      3 months, they were tested for locomotor activity after an i.p. injection of one
      of psychoactive drugs: D-amphetamine (5.0 mg/kg), apomorphine (2.0 mg/kg),
      dizocilpine (0.25 mg/kg), or caffeine (30 mg/kg). Mice submitted to the LP diet
      presented prolonged induction of hyperlocomotion caused by amphetamine (about
      350% between 90 and 180 min post drug injection as compared with well-nourished
      mice, p<0.01) but presented unaltered response to apomorphine, caffeine, and
      dizocilpine. These data point to altered catecholamine metabolism induced by
      protein restriction in adult mice. The results are discussed based on previous
      works, presenting theoretical hypotheses about the possible mechanisms involved
      in the present findings.

PMID- 15501500
TI  - Acute and chronic stress influence blood pressure variability in mice.
AB  - There is evidence that alterations in heart rate and blood pressure variability
      (BPV) are associated with cardiovascular disease. We used a mice model to
      investigate the effects of acute and chronic stress on blood pressure variability
      (BPV) and heat rate variability (HRV). Shaker stress was given acutely (5 min,
      150 cycles/min) and chronically (3 days, 2 min stress, 150 cycles/min, 45
      sessions/day) in male C57BLJ mice. Systolic arterial pressure (SAP) and pulse
      interval (PI) time series were submitted to autoregressive spectral analysis with
      variability measured in the low-frequency (LF, 0.1-1.0 Hz) and high-frequency
      (HF, 1-5 Hz) ranges. In the acute experiment, MAP was increased significantly in
      the first 10 min poststress period (99+/-2 vs. 113+/-2 mm Hg) and returned to
      control levels 30 min poststress. HR was significantly higher in the initial
      poststress period (537+/-12 vs. 615+/-20 bpm). These alterations were associated
      with a marked increase in BPV (21+/-4 vs. 55+/-11 mm Hg2) and in power of LF
      oscillations (18+/-3 vs. 42+/-7 mm Hg2). On the other hand, chronic stress
      exposure produced a reduction in BPV (16+/-4 vs. 6+/-1 mm Hg2) and LF
      oscillations (11+/-3 vs. 3+/-1 mm Hg2). HRV was not altered after either acute or
      chronic stress. Spontaneous baroreflex sensitivity (SBS), determined by cross
      spectral analysis between PI and BP, was reduced significantly in acute stress (
      50%), but unchanged in chronic stress. Our results show that acute stress
      produced changes in BPV that may be associated with increased sympathetic
      activity and a reduction in blood pressure buffering. Under chronic conditions,
      there is no alteration in baroreflex sensitivity while BPV is reduced. This is
      likely related to the combination of sympathetic activation in the face of
      vasculature alterations.

PMID- 15501501
TI  - Differential dose effects of central CRF and effects of CRF astressin on pig
      behavior.
AB  - The elevation of central corticotropin releasing factor (CRF) causes an increase
      in behavioral activity, including increases in overall activity and
      oral/nasal/facial (ONF) chewing-rooting-rubbing behaviors in the pig and similar
      behaviors in other species. This study detailed changes in the frequency,
      duration and sequences of behaviors after central administration of vehicle or
      porcine CRF (pCRF at 0.5, 5.0, 50 and 150 microg). A sequential analysis
      described the complex behaviors induced in a dose-dependent fashion by central
      pCRF. The frequency and duration of ONF behaviors were significantly increased
      among pigs receiving 50 microg of pCRF. For behaviors such as ONF, 50 microg
      represented a breakpoint at which the frequency and duration of single behaviors
      increased. Pigs receiving 50 microg of pCRF were considerably more active and
      exhibited more ONF behaviors than did pigs receiving lower doses. The highly
      sensitive sequential analysis revealed that very low doses of central pCRF
      induced subtle changes in sequences of behaviors. Low doses of central pCRF (0.5
      microg) induced fear-related behavioral sequences that included ONF behaviors
      alternating with periods of inactivity. Central injection of astressin, a CRF
      receptor antagonist, blocked many, but not all, of CRF-induced behaviors.
      Compared with saline-injected control pigs, central pCRF increased general
      activity, ONF, fear-related freezing and sham chewing behaviors. When pCRF was
      given following astressin, fear-related freezing behaviors were not different
      compared with pigs receiving saline. However, pigs given astressin plus pCRF
      showed elevated sham chewing compared with saline-injected control pigs, as did
      pigs receiving intracerebroventricular (ICV) pCRF. These data indicate that
      central pCRF activates brain mechanisms associated with hyperactivity, ONF and
      fear-related behaviors, whereas other behaviors induced by pCRF may be
      nonspecifically mediated by CRF. Astressin antagonized some, but not all, pCRF
      induced behaviors. This model represents the induction of hyperactivity and
      stereotyped behaviors, which may represent a new model for the study of mania or
      obsessive-compulsive behaviors.

PMID- 15501503
TI  - Modulation of the pair housing induced feeding suppression.
AB  - The present experiments explored how manipulating the period of individual
      housing, partner novelty, or short periods of conspecific interaction affected
      the feeding suppression evident when young adult male rats were moved from
      individual to pair housing. In the first experiment, after a period of pair
      housing, rats were individually housed for 0, 3, 10, or 14 days before being
      rehoused with either the same or a novel partner. There was an increase in the
      feeding suppression as the duration of individual housing grew, and at 3 days,
      the novel partner produced a stronger suppression than did the familiar partner.
      In the second experiment, four 15-min exposures to a conspecific in a novel place
      preference environment did not eliminate the feeding suppression at pair housing.
      The third experiment found that four 90-min exposures to a conspecific reduced
      the feeding suppression evident at rehousing. In Experiments 2 and 3, an
      environment previously paired with a conspecific did not produce a place
      aversion. Together, these experiments suggest that the feeding suppression
      evident when male rats are moved from individual to pair housing can be
      considered a graded effect open to modulation by a variety of behavioral
      manipulations.

PMID- 15501502
TI  - Differential activity of drugs to induce emesis and pica behavior in Suncus
      murinus (house musk shrew) and rats.
AB  - We have previously reported that emetic stimuli induce kaolin ingestion behavior
      (pica behavior) in rats and mice (i.e., species that do not have the emetic
      reflex) and that the behavior may be analogous to gastrointestinal discomfort,
      such as nausea and emesis. We hypothesized that pica behavior may also occur in
      species capable of vomiting and that it may serve as an additional index of
      discomfort relevant to antiemetic drug development. The present experiments were
      conduced using Suncus murinus and rats and kaolin consumption was measured at 24
      h after the administration of nicotine (1.25-5 mg/kg, s.c.), copper sulfate (10
      120 mg/kg, p.o.), lithium chloride (50-200 mg/kg, i.p.) and cisplatin (1-30
      mg/kg, i.p.). In S. murinus, all treatments, excepting lithium chloride, were
      emetic but none induce kaolin consumption. Conversely, all treatments induced
      kaolin consumption in rats without inducing emesis. The results indicate that
      pica behavior is not likely to be useful to assess gastrointestinal discomfort in
      S. murinus.

PMID- 15501504
TI  - Physical training reverts hippocampal electrophysiological changes in rats
      submitted to the pilocarpine model of epilepsy.
AB  - Physical exercise and fitness programs in patients with epilepsy are still a
      matter of controversy. Effects of physical exercise in animals with epilepsy have
      been demonstrated. To further investigate the possible mechanisms by which
      physical activity interferes with epileptogenesis, the present work was aimed to
      study the effect of aerobic exercise on "in vitro" hippocampal
      electrophysiological parameters observed in rats submitted to the pilocarpine
      model of epilepsy. Electrophysiological changes were monitored by extracellular
      field potentials recorded from CA1 area. Control rats and rats with epilepsy were
      submitted to an aerobic exercise program. The number of population spikes (PS)
      and slope of field excitatory postsynaptic potentials (fEPSP) were analyzed.
      Trained rats with epilepsy exhibited a reduction in PS when compared with
      nontrained rats with epilepsy in different concentrations of extracellular
      potassium or bicuculline. Physical training also enhanced the late phase of LTP
      in rats with epilepsy. Our results indicate that physical training reduces CA1
      hyperresponsiveness and can modify synaptic plasticity in rats submitted to the
      pilocarpine model of limbic epilepsy.

PMID- 15501505
TI  - Computer-based extraction of the inferior alveolar nerve canal in 3-D space.
AB  - Computed tomography (CT) is increasingly employed in orthodontic treatment. One
      of the most successful applications is in dental implantology, in which an
      artificial root is surgically inserted into the jawbone to provide anchorage for
      a dental prosthesis. For successful implant surgery, it is crucial to locate
      internal structures such as the inferior alveolar nerve canal (IAC). This paper
      presents a computerized technique for extracting the IAC. To facilitate the
      extraction, we first generate panoramic CT images (panoramics) by reformatting
      the original CT images. The panoramics are a series of cross-sectional images
      along curved planes through the mandible (lower jawbone). Hollow canals are
      subsequently detected by analyzing the voxel intensities and 3-D gradient
      orientations in the panoramics. The axis of the IAC is then traced out by a novel
      3-D line-tracking technique. The method is effective for extracting the IAC
      despite the open structure of the surrounding bone.

PMID- 15501506
TI  - Simulating growth dynamics and radiation response of avascular tumour spheroids
      model validation in the case of an EMT6/Ro multicellular spheroid.
AB  - The goal of this paper is to provide both the basic scientist and the clinician
      with an advanced computational tool for performing in silico experiments aiming
      at supporting the process of biological optimisation of radiation therapy.
      Improved understanding and description of malignant tumour dynamics is an
      additional intermediate objective. To this end an advanced three-dimensional (3D)
      Monte-Carlo simulation model of both the avascular development of multicellular
      tumour spheroids and their response to radiation therapy is presented. The model
      is based upon a number of fundamental biological principles such as the
      transition between the cell cycle phases, the diffusion of oxygen and nutrients
      and the cell survival probabilities following irradiation. Efficient algorithms
      describing tumour expansion and shrinkage are proposed and applied. The output of
      the biosimulation model is introduced into the (3D) visualisation package AVS
      Express, which performs the visualisation of both the external surface and the
      internal structure of the dynamically evolving tumour based on volume or surface
      rendering techniques. Both the numerical stability and the statistical behaviour
      of the simulation model have been studied and evaluated for the case of EMT6/Ro
      spheroids. Predicted histological structure and tumour growth rates have been
      shown to be in agreement with published experimental data. Furthermore, the
      underlying structure of the tumour spheroid as well as its response to
      irradiation satisfactorily agrees with laboratory experience.

PMID- 15501507
TI  - Automated eye tracking system calibration using artificial neural networks.
AB  - The electro-oculogram (EOG) continues to be widely used to record eye movements
      especially in clinical settings. However, an efficient and accurate means of
      converting these recordings into eye position is lacking. An artificial neural
      network (ANN) that maps two-dimensional (2D) eye movement recordings into 2D eye
      positions can enhance the utility of such recordings. Multi-layer perceptrons
      (MLPs) with non-linear activation functions and trained with back propagation
      proved to be capable of calibrating simulated EOG data to a mean accuracy of 0.33
      degrees . Linear perceptrons (LPs) were only nearly half as accurate. For five
      subjects, the mean accuracy provided by the MLPs was 1.09 degrees of visual angle
      ( degrees ) for EOG data, and 0.98 degrees for an infrared eye tracker. MLPs
      enabled calibration of 2D saccadic EOG to an accuracy not significantly different
      from that obtained with the infrared tracker. Using initial weights trained on
      another person reduced MLP training time, reaching convergence in as little as 20
      iterations.

PMID- 15501508
TI  - PREDICTOL: a computer program to determine the thermophysiological duration
      limited exposures in various climatic conditions.
AB  - PREDICTOL is a PC program used to determine the thermophysiological duration
      limited exposures (DLE) in humans, nude or clothed, submitted to various climatic
      conditions (hot and cold climates) at rest or during a physical exercise. DLE are
      determined following different standards of the International Standardization
      Organization (ISO), especially ISO 7933 for hot environment and ISO-TR 11079 for
      cold environment. The original aspect of this program is that it can be used
      whatever the climatic conditions. The program presents two modes: an educational
      interactive mode and a scenario mode. The educational interactive mode
      demonstrates the thermophysiological effects, expressed as DLE, of different
      parameter changes (temperature, humidity, wind speed, metabolic heat production
      by physical exercise, clothing insulation and water vapor permeability). The
      scenario mode determines DLE for given various linked sequences as encountered in
      occupational, military or even recreational activities, each sequence being
      characterized by its climatic conditions, physical activities performed and by
      physical clothing properties. DLE given by PREDICTOL are correlated to those
      obtained in various controlled climatic laboratory conditions (r = 0.86; P <
      0.001). PREDICTOL is written in Visual Basic 6.0. A "help menu" is provided to
      explain the use of the program and give information concerning the equations used
      to calculate both the thermal balance and DLE.

PMID- 15501509
TI  - A study on the reference electrode standardization technique for a realistic head
      model.
AB  - One oldest technical problem in EEG practice is the effect of an active reference
      on EEG recording, and it is especially important for identifying the temporal
      information of EEG recordings. To solve this problem, a reference electrode
      standardization technique (REST) has been proposed for a concentric three-sphere
      head model. REST, based on an equivalent distributed source model, reconstructs
      the potential with a reference at infinity from the potential with a scalp point
      reference or with the average reference. In this paper, investigated was the REST
      for a realistic head model. The results of simulation studies show that the
      potential reconstruction for the realistic head model is more sensitive to noise
      than that for the concentric three-sphere head model, so a regularized inverse by
      truncated singular value decomposition was introduced. The results confirm that
      REST is still an efficient method even for a realistic head model especially for
      the most important superficial cortex region.

PMID- 15501510
TI  - Spike detection, characterization, and discrimination using feature analysis
      software written in LabVIEW.
AB  - Rapid and accurate discrimination of single units from extracellular recordings
      is a fundamental process for the analysis and interpretation of
      electrophysiological recordings. We present an algorithm that performs detection,
      characterization, discrimination, and analysis of action potentials from
      extracellular recording sessions. The program was entirely written in LabVIEW
      (National Instruments), and requires no external hardware devices or a priori
      information about action potential shapes. Waveform events are detected by
      scanning the digital record for voltages that exceed a user-adjustable trigger.
      Detected events are characterized to determine nine different time and voltage
      levels for each event. Various algebraic combinations of these waveform features
      are used as axis choices for 2-D Cartesian plots of events. The user selects axis
      choices that generate distinct clusters. Multiple clusters may be defined as
      action potentials by manually generating boundaries of arbitrary shape. Events
      defined as action potentials are validated by visual inspection of overlain
      waveforms. Stimulus-response relationships may be identified by selecting any
      recorded channel for comparison to continuous and average cycle histograms of
      binned unit data. The algorithm includes novel aspects of feature analysis and
      acquisition, including higher acquisition rates for electrophysiological data
      compared to other channels. The program confirms that electrophysiological data
      may be discriminated with high-speed and efficiency using algebraic combinations
      of waveform features derived from high-speed digital records.

PMID- 15501511
TI  - SignalML: metaformat for description of biomedical time series.
AB  - This paper introduces a complete and elegant solution to the problem of inherent
      incompatibility of different formats used for digital storage of biomedical time
      series (in particular EEG) and their annotations. We define a simple XML-based
      language, in which information on the structure of binary data files can be
      simply and efficiently coded. In most cases, description of an existing format
      takes relatively few lines of XML code. Once written, this information can be
      used by any software, which, owing to this meta-description, may read the
      original data files, thus eliminating the need for conversions and duplication of
      data. This proposition is hereby submitted to an open discussion within the
      community involved in relevant research, clinical and commercial applications.
      Links to the current version of the XML Schema defining the language and pilot
      implementation of a compliant viewer/annotator are located at
      http://eeg.pl/SignalML/.

PMID- 15501512
TI  - SignalML from an EDF+ perspective.
AB  - Both SignalML and EDF+ offer a solution for the incompatibility between different
      data storage formats in biomedicine. This article discusses the SignalML approach
      from an EDF+ point of view.

PMID- 15501513
TI  - Identification of a peptide binding motif for secreted frizzled-related protein
      1.
AB  - Secreted Frizzled-related proteins (sFRPs) bind Wnts and modulate their activity.
      To identify putative sFRP-1 binding motifs, we screened an M13 phage displayed
      combinatorial peptide library. A predominant motif, L/V-VDGRW-L/V, was present in
      approximately 70% of the phage that bound sFRP-1. Use of peptide/alkaline
      phosphatase chimeras and alanine scanning confirmed that the conserved motif was
      important for sFRP-1 recognition. The dissociation constant for a peptide/sFRP-1
      complex was 3.9 microM. Additional analysis revealed that DGR was the core of the
      binding motif. Although Wnt proteins lack this sequence, other proteins
      possessing the DGR motif may function as novel binding partners for sFRP-1.

PMID- 15501514
TI  - Antibacterial hemoglobin peptides in human menstrual blood.
AB  - This work documents that normal menstrual vaginal blood of healthy females is
      exceptionally rich in hemocidins--hemoglobin (Hb) fragments having bactericidal
      properties. The peptide fractions were isolated from the plasma of vaginal
      discharge of three healthy nulliparous women and subjected to identification by
      automatic sequencing as well as by mass spectrometry. All 44 identified peptides
      originate from Hb (mainly from the N-terminal part of alpha-globin) and all
      demonstrated differential killing activity toward Escherichia coli. The screening
      of antimicrobial activity was performed using two synthetic peptides identical to
      those found in menstrual blood. These peptides were active mainly toward Gram
      negative bacteria and to a less degree toward Gram-positive bacteria. Our results
      confirm recent observations that Hb-derived fragments manifest pronounced
      antibacterial activity and suggest that these peptides help in maintaining human
      vaginal homeostasis during physiologic menstrual bleeding.

PMID- 15501515
TI  - Mammalian thioredoxin reductase alters cytolytic activity of an antibacterial
      peptide.
AB  - Granulysin is a disulfide rich 9 kDa human tumoricidal protein produced by
      cytolytic cells. Here we show that thioredoxin reductase (TrxR) reduced a 23
      residue peptide from granulysin (GranF2), and this markedly enhanced the killing
      of small cell lung cancer cells (SCLC) by GranF2. Cells treated with reduced
      GranF2 showed rapid ATP deletion within 90 min and strong annexin V staining
      after 4 h incubation. SCLC with elevated TrxR levels was more sensitive to
      oxidized GranF2 than normal cells. The levels of TrxR are enhanced in many cancer
      cells, including SCLC, and it is possible that cytolytic activity of cytolytic
      cells on SCLC may in part be mediated by granulysin and modulated by TrxR.

PMID- 15501516
TI  - Polyprotein cleavage mechanism of SARS CoV Mpro and chemical modification of the
      octapeptide.
AB  - The cleavage mechanism of severe acute respiratory syndrome (SARS) coronavirus
      main proteinase (M(pro) or 3CL(pro)) for the octapeptide AVLQSGFR is studied
      using molecular mechanics (MM) and quantum mechanics (QM). The catalytic dyad His
      41 and Cys-145 in the active pocket between domain I and II seem to polarize the
      pi-electron density of the peptide bond between Gln and Ser in the octapeptide,
      leading to an increase of positive charge on C(CO) of Gln and negative charge on
      N(NH) of Ser. The possibility of enhancing the chemical bond between Gln and Ser
      based on the "distorted key" theory [Anal. Biochem. 233 (1996) 1] is examined.
      The scissile peptide bond between Gln and Ser is found to be solidified through
      "hybrid peptide bond" by changing the carbonyl group CO of Gln to CH(2) or CF(2).
      This leads to a break of the pi-bond system for the peptide bond, making the
      octapeptide (AVLQSGFR) a "distorted key" and a potential starting system for the
      design of anti SARS drugs.

PMID- 15501517
TI  - Computational peptide dissection of Melan-a/MART-1 oncoprotein antigenicity.
AB  - We have mapped the linear antigenic determinant of a commercial MAb raised in the
      mouse against the melanoma-associated-antigen Melan-A/MART-1. The B cell epitope
      on the Melan-A/MART-1 oncoprotein is located in the 15-mer amino acid sequence
      101-115 PPAYEKLSAEQSPPP, within residues 102-106. The definition of the antigenic
      sequence on Melan-A/MART-1 oncoprotein was reached following analyses of MHC II
      binding potential and similarity level to the mouse proteome, that put into
      evidence the 15-mer amino acid sequence 101-115 PPAYEKLSAEQSPPP as the top
      scoring peptide in binding H2-A(d) molecules and the epitopic sequence residues
      102-106 (i.e., the peptide sequence PAYEK) as having low-similarity level to the
      mouse proteome. Dot-blot epitope mapping immunoassay identified proline residue
      102 as critical, based on its effect on antibody recognition. The present study
      adds to previous companion reports in validating the hypothesis that low
      similarity to the host's proteome and binding potential to MHC II molecules are
      essential concurring factors in the modulation of the pool of epitopic sequences.

PMID- 15501518
TI  - Efficacy of human beta-casein fragment (54-59) and its synthetic analogue
      compound 89/215 against Leishmania donovani in hamsters.
AB  - The characteristic feature of visceral leishmaniasis (VL) is the profound
      impairment of immune system of the infected host, which contributes significantly
      to the partial success of antileishmanial chemotherapy. Since in VL, cure is the
      combinatorial effect of drug and immune status of the host, the rationale
      approach towards antileishmanial chemotherapy would be to potentiate the immune
      functioning of the host to extract desired results. Towards this direction
      several rationally designed analogues of human beta-casein fragment (54-59) were
      evaluated for their ability to stimulate the non-specific resistance in hamsters
      against Leishmania donovani infection. By virtue of being derived from the food
      protein casein derivatives may be devoid of unwanted side effects associated with
      the substances of microbial origin, e.g. muramyl dipeptide (MDP). Out of this one
      peptide Val-Glu-Gly-Ile-Pro-Tyr (compound 89/215) had been reported to have such
      activity. In this communication, the prophylactic and therapeutic efficacy of the
      peptide along with its natural sequence has been evaluated in detail against
      experimental VL in hamsters. Their use as an adjunct to chemotherapy was also
      explored. Human beta-casein fragment, compound 89/215 and MDP were tested in vivo
      at various dose levels wherein compound 89/215 showed superiority over MDP at 3
      mg/kg x 2 given intraperitoneally (i.p.). Compound 89/215 sensitized peritoneal
      macrophages acquired considerable resistance and only 24% of the cells were found
      infected in comparison to control peritoneal macrophages where 76.4% of the cells
      were found infected. Similarly, the efficacy of sodium antimony gluconate (SAG)
      in hamsters pretreated with compound 89/215 enhanced significantly (P < 0.001).
      This peptide also exhibited considerably good therapeutic efficacy when evaluated
      either alone or in combination with SAG in established infection of L. donovani.

PMID- 15501519
TI  - The cDNA for leucomyosuppressin in Blattella germanica and molecular evolution of
      insect myosuppressins.
AB  - Myosuppressins are a group of 10-residues FMRFamide-related peptides reported in
      Dictyoptera, Orthoptera, Lepidoptera and Diptera. Myosuppressins inhibit visceral
      muscle contractions and, in the cockroach Blattella germanica, inhibit food
      intake. In B. germanica, the cDNA of leucomyosuppressin (LMS) has been cloned and
      sequenced. The deduced precursor is 96 amino acids long and contains a single
      copy of LMS. Brain mRNA levels remain constant during the first reproductive
      cycle of adult females, whereas those in the gut show a slight decline during the
      time of maximal food intake. Comparison of myosuppressin precursors of different
      species reveals that all have the same organization. Phylogenetic analysis
      suggests that the precursor experienced an accelerated evolution in Lepidoptera
      and Diptera with respect to Dictyoptera, whereas only Lepidoptera has radical
      changes in the bioactive peptide.

PMID- 15501520
TI  - Evidence for brain-derived neurotrophic factor-like neuropeptide in brain of the
      silk moth Bombyx mori during postembryonic periods.
AB  - Brain-derived neurotrophic factor-like neuropeptide is produced in the brain of
      the silk moth, Bombyx mori. Immunocytochemical studies of brain and retrocerebral
      complex of larvae, prepupae, pupae and adults showed that four pairs of median
      neurosecretory cells and six pairs of lateral neurosecretory cells which had
      different immunoreactivities to BDNF peptide. Day-1 adult brains showed no
      evidence of neurons stained by anti-BDNF antibodies. Those reactivities, which
      were much stronger in median cells than in lateral cells, were the weakest in an
      earliest larval stage and a latest pupal stage but the strongest in late larval
      stage. Median neurosecretory cells projected their axons into the contralateral
      corpora allata by decussation in the median region, nerve corpora cardiaca (NCC)
      I, and nerve corpora allata (NCA) I, whereas lateral neurosecretory cells
      extended their axons to the ipsilateral corpora allata via NCC II and NCA I.

PMID- 15501521
TI  - The crustacean hyperglycemic hormone precursors a and b of the Norway lobster
      differ in the preprohormone but not in the mature peptide.
AB  - The neuro-endocrine X-organ sinus-gland complex of crustaceans produces and
      releases the neuropeptides of the crustacean hyperglycemic hormone (cHH)/molt
      inhibiting hormone (MIH)/gonad-inhibiting hormone (GIH) family that regulate
      important physiological processes, such as growth, reproduction and molting. We
      cloned two full-length cDNAs encoding the preprocHH-A and preprocHH-B of the
      Norway lobster Nephrops norvegicus of 132 and 131 amino acid residues. The two
      cHHs differ in the preprohormone but not in the mature peptide sequence. The
      mature cHH was expressed in bacteria as GST fusion protein that, in bioassay,
      shows a hyperglycemic activity similar to that of native cHH present in an
      eyestalk extract.

PMID- 15501522
TI  - A role of anti-verotoxin antibody immunoreactive peptide, Virp5, from rat spinal
      cord.
AB  - An anti-verotoxin 2 (VT2) antibody immunoreactive 5-kDa polypeptide (Virp5), has
      been obtained through screening of the rat spinal cord cDNA library with the aid
      of anti-VT2 antibody. Virp5 was mainly expressed in the central nervous system,
      liver and kidney, and localized at glia-like cells and nerve fibers in the
      central nervous system, vascular endothelial cells and hepatic cells in the
      liver, as well as epithelial cells of distal tubules in the kidney. Intravenous
      administration of purified Virp5 elicited a dose-dependent increase in blood
      pressure. These results suggest that Virp5 commonly exists in the body, being
      partly playing a role in regulating the blood pressure.

PMID- 15501523
TI  - The thrombin peptide, TP508, enhances cytokine release and activates signaling
      events.
AB  - The thrombin peptide, TP508, accelerates tissue repair and initiates a cascade of
      cellular events. We have previously shown that alpha-thrombin induces cytokine
      expression in human mononuclear cells. We, therefore, investigated the
      possibility that TP508 might activate cytokine production and intracellular
      signaling pathways associated with cytokine activation. Our results show that
      TP508 induces cytokine expression in human mononuclear cells. TP508 treatment
      enhances extracellular signal-regulated kinase (Erk1/2) activities in U937 cells,
      as well as Erk1/2 and p38 activation in Jurkat T cells. These data support the
      hypothesis that TP508 may accelerate tissue repair through the activation of the
      inflammatory response.

PMID- 15501524
TI  - Diurnal levels of Fos immunoreactivity are elevated within hypocretin neurons in
      lactating mice.
AB  - The hypocretins modulate arousal via actions across multiple terminal fields.
      Thus, alterations in hypocretin neurotransmission may contribute to altered sleep
      patterns observed during lactation. This study examined whether lactation is
      associated with alterations in the number of hypocretin neurons and in diurnal
      Fos-immunoreactivity within hypocretin neurons in female mice. Alterations in Fos
      immunoreactivity were also examined within two hypocretin terminal regions; the
      medial preoptic area and the locus coeruleus. Fos-immunoreactivity was increased
      within hypocretin neurons and the medial preoptic area in lactating females. No
      differences were observed in the number of hypocretin neurons or in Fos
      immunoreactivity within the locus coeruleus.

PMID- 15501525
TI  - Systemic and intra-dorsal periaqueductal gray injections of cholecystokinin
      sulfated octapeptide (CCK-8s) induce a panic-like response in rats submitted to
      the elevated T-maze.
AB  - The neuropeptide cholecystokinin (CCK) has been implicated in fear and anxiety.
      CCK is found in the CNS in several molecular forms such as the tetrapeptide (CCK
      4) and, mainly, the sulfated octapeptide (CCK-8s) fragments. Administration of
      CCK-4 induces panic attacks in humans and increases the expression of different
      anxiety-related behaviors in laboratory animals. The effects of CCK-8s on fear
      and anxiety are less straightforward and seem to be influenced, among other
      factors, by the route of the peptide administration and the animal model
      employed. In other to further investigate the role of CCK-8s in fear and anxiety,
      in the present study we analyzed the effect of CCK-8s in male Wistar rats
      submitted to the elevated T-maze. This animal model of anxiety was developed in
      order to separate generalized anxiety (inhibitory avoidance) and panic-like
      (escape) responses in the same rat. The effect of CCK-8s in this test was also
      investigated after injection of the peptide into the dorsal periaqueductal gray
      (DPAG). This brainstem area is rich in CCK receptors and has consistently been
      implicated in the mediation of fear and anxiety responses. The results showed
      that both the intraperitoneal and intra-DPAG injections of CCK-8s potentiated one
      way escape behavior, suggesting a panicogenic action. In contrast, the injection
      of the CCK2 receptor antagonist CR2945 inhibited the expression of this behavior,
      a panicolytic-like effect. Therefore, the elevated T-maze, in contrast to other
      animal models of anxiety, can detect the anxiety-eliciting effects of CCK-8s both
      after its systemic and central administration. Also, the results provide further
      evidence about the involvement of a CCK-mediated mechanism within the DPAG in the
      regulation of panic-related defensive behaviors.

PMID- 15501526
TI  - Ac His1 [D-Phe2, K15, R16, L27] VIP (3-7)/GRF (8-27)--a VPAC1 receptor antagonist
      -is an inverse agonist on two constitutively active truncated VPAC1 receptors.
AB  - C-terminally truncated human VPAC(1) receptors were constructed and stably
      transfected in Chinese hamster ovary (CHO) cells. Selected clones expressing
      comparable receptor densities were studied for ligand's binding properties, basal
      and stimulated adenylate cyclase activity. The wild-type (1-457) receptor served
      as reference. The binding properties of all the constructions were preserved. As
      judged by the intrinsic activity of the partial agonist Q(3)-VIP, the shortest
      receptors have a moderate impairment of the coupling efficacy to G(alpha s)
      protein. Cells expressing the VPAC(1) (1-436) and (1-441) truncated receptors had
      a two- to three-fold higher basal adenylate cyclase activity than those
      expressing the wild-type or the VPAC(1) (1-444), (1-433), (1-429), (1-421) and (1
      398) receptor. The stimulatory effect of VIP and other agonist was preserved.
      This suggested that VPAC(1) (1-436) and (1-441) receptors had a constitutive
      activity. The selective VPAC(1) receptor antagonist Ac His(1) [D-Phe(2), K(15),
      R(16), L(27)] VIP (3-7)/GRF (8-27) reduced by 60% the basal activity with an
      EC(50) value of 3 nM comparable to its IC(50) value for binding. This agonist
      behaved thus like an inverse agonist on the constitutively active VPAC(1)
      receptors generated by C-terminal truncation and expressed in CHO cells.

PMID- 15501527
TI  - The substance P (SP) heptapeptide fragment SP1-7 alters the density of dopamine
      receptors in rat brain mesocorticolimbic structures during morphine withdrawal.
AB  - The aminoterminal fragment of substance P (SP), SP(1-7), has been suggested to
      modulate the expression of opiate tolerance and withdrawal behaviors in rodents.
      However, the mechanism of this effect is not yet clarified. Using a rat model we
      have previously demonstrated that SP(1-7) affects dopamine transmission and the
      expression of the dopamine D2-receptor gene transcript in the nucleus accumbens
      during naloxone precipitated morphine withdrawal. In the present study, we have
      applied autoradiography to investigate the effect of the heptapeptide on the
      binding of dopamine D1- and D2-receptors in mesocorticolimbic brain areas of male
      rats during morphine withdrawal. Morphine dependent animals were treated with an
      injection of SP(1-7) into the ventral tegmental area prior to naloxone challenge.
      The result indicated that the SP fragment elicited a significant decrease in
      specific binding to D1-like receptors in the caudate putamen, nucleus accumbens
      shell, nucleus accumbens core, substantia nigra and medial globus pallidus.
      Radioligand binding to dopamine D2-like receptors was also altered by SP(1-7).
      The heptapeptide induced a decreased density of these sites in the ventral
      tegmental area but an increased binding in the substantia nigra and the frontal
      cortex. The observed alterations in the D1- and D2-like receptor density could
      reflect activations in dopamine pathways associated with the above-mentioned
      brain regions. The result provides further evidence for the modulatory effect of
      SP(1-7) on dopamine systems during opioid withdrawal, suggesting the possible
      role for the heptapeptide to regulate morphine withdrawal reactions.

PMID- 15501528
TI  - Neurokinin-1 receptor antagonism by SR140333: enhanced in vivo ACh in the
      hippocampus and promnestic post-trial effects.
AB  - Substance P (SP) has memory-promoting, reinforcing and anxiolytic-like effects
      when applied systemically or centrally. Such effects may be mediated by the
      neurokinin-1 (NK-1) receptor, since SP preferentially binds to this receptor. We
      measured the effects of a selective non-peptide NK-1 receptor antagonist,
      SR140333 (1, 3 and 9 mg/kg i.p.) on ACh levels in frontal cortex, amygdala and
      hippocampus by microdialysis and HPLC. Levels of ACh in the hippocampus increased
      dose-dependently immediately after treatment. The same doses of SR140333 given
      post-trial had minor facilitative effects on inhibitory avoidance learning and
      open-field habituation, but did not have reinforcing effects in a conditioned
      place preference (CPP) task. The selective action of NK-1 receptor antagonism on
      hippocampal ACh may be related to its positive influence on learning.

PMID- 15501529
TI  - Eledoisin and Kassinin, but not Enterokassinin, stimulate ion transport in frog
      skin.
AB  - In frog skin, tachykinins stimulate the ion transport, estimated by measuring the
      short-circuit current (SCC) value, by interacting with NK1-like receptors. In
      this paper we show that Kassinin (NK2 preferring in mammals) increases the SCC,
      while Enterokassinin has no effect. Therefore, either 2 Pro residues or 1 Pro and
      1 basic amino acid must be present in the part exceeding the C-terminal
      pentapeptide. Eledoisin (NK3 preferring in mammals) stimulation of SCC is reduced
      by CP99994 and SR48968 (NK1 and NK2 antagonists) and not affected by SB222200
      (NK3 antagonist). None of the three antagonists affects Kassinin stimulation of
      SCC.

PMID- 15501530
TI  - Urotensin-II activates L-arginine/nitric oxide pathway in isolated rat aortic
      adventitia.
AB  - Urotensin-II (U-II), a cyclic peptide widely expressed in blood vessels, has
      diverse vascular actions that range from potent vasoconstriction to vasodilation.
      Although, U-II-induced vasodilation has been shown to be partially dependent on
      nitric oxide (NO), the involvement of vascular adventitia-derived NO, remains
      unknown. The present study aimed to elucidate the activation of U-II on L
      arginine/NO pathway in isolated rat aortic adventitia. In adventitia of thoracic
      and abdominal aortas, the l-arginine/NO pathway was similarly characterized: the
      uptake of l-[(3)H]arginine was Na(+)-independent, with the peak occurring over
      around 40 min incubation; the total NO synthase (NOS) activity was mostly calcium
      independent (>90%), and significantly inhibited by a specific iNOS inhibitor AMT;
      the production of NO metabolites nitrate and nitrite (NO(x)) was stimulated by L
      arginine but not by D-arginine. In aortic adventitia exposed to rat U-II (10(-9)
      and 10(-8)M) for 6 h, the V(max) of l-[(3)H]arginine uptake over 40 min
      incubation was significantly increased, while the K(m) of l-[(3)H]arginine uptake
      showed no significant change. Besides, the iNOS mRNA level was up-regulated, the
      total NOS activity, largely calcium-independent, was significantly induced, and
      the NO(x) production was significantly stimulated by U-II. According to the same
      protocol as U-II, the positive control lipopolysaccharide (LPS, 10 microg/ml),
      which had been established to activate adventitial L-arginine/NO pathway,
      increased l-[(3)H]arginine uptake, iNOS activity and NO(x) production to a
      greater extent than U-II. In addition, the total NOS activities induced by 3 and
      6h incubation of U-II and LPS were significantly inhibited by a specific
      inhibitor of protein synthesis, actinomycin D. In conclusion, the results showed
      that rat U-II activated L-arginine/NOS/NO pathway in rat aortic adventitia,
      suggesting a potential contributive role of adventitia-derived NO in the
      vasodilator response of U-II.

PMID- 15501531
TI  - Mechanisms underlying enhanced contractile response to endothelin-1 in diabetic
      rat basilar artery.
AB  - We investigated the influence of streptozotocin-induced diabetes on the
      responsiveness of the rat basilar artery to endothelin-1 (ET-1) and nitric oxide
      (NO), which is known to counteract ET-1. In basilar arteries isolated from
      diabetic rats: (a) the ET-1-induced contraction was enhanced, (b) the contraction
      induced by N(G)-nitro-l-arginine [a nitric oxide synthase (NOS) inhibitor] was
      weaker, and (c) the levels of the mRNAs for ET(A)/ET(B) receptors and prepro-ET
      1, but not for NOS, were significantly elevated (all versus age-matched
      controls). These data indicate that ET-1-induced vasoconstriction may be
      increased in the diabetic rat basilar artery, and that this hyper-reactivity to
      ET-1 may be due to an overproduction of ET-1, an up-regulation of ET(A)/ET(B)
      receptors, and a defect in the bioavailability of NO.

PMID- 15501532
TI  - Intracerebroventricular injection of neuropeptide EI increases serum LH in male
      and female rats.
AB  - Melanin concentrating hormone (MCH) precursor-derived neuropeptide EI (NEI) has
      not yet been extensively studied. The aim of this study was to determine the
      effect of neuropeptide EI on serum levels of LH in normal male rats and
      chronically ovariectomized (CHR-OVX) female rats treated with estrogen benzoate
      (EB) and with a low dose of progesterone. The peptide, administered
      intracerebroventricularly in male and chronically ovariectomized female rats,
      increased LH serum levels compared to the controls injected with artificial
      cerebrospinal fluid. It is important to note that there is some relation between
      neuropeptide EI-melanin concentrating hormone and alpha-melanocyte stimulating
      hormone (alpha-MSH) indicating that all three peptides are associated in a
      complex inter-relationship. Therefore, the question that arises is if
      neuropeptide EI could also be related with the receptors for melanin
      concentrating hormone or alpha-melanocyte stimulating hormone.

PMID- 15501533
TI  - Introductory notes. Old and new paradigms in the field of the calcitonin family
      of peptides.

PMID- 15501534
TI  - Adrenomedullin receptors: pharmacological features and possible
      pathophysiological roles.
AB  - Three receptor activity modifying proteins (RAMPs) chaperone calcitonin-like
      receptor (CLR) to the cell surface. RAMP2 enables CLR to form an adrenomedullin
      (AM)-specific receptor that is sensitive to AM-(22-52) (AM(1) receptor). RAMP3
      enables CLR to form an AM receptor sensitive to both calcitonin gene-related
      peptide (CGRP)-(8-37) and AM-(22-52) (AM(2) receptor), though rat and mouse AM(2)
      receptors show a clear preference for CGRP alpha-(8-37) over AM-(22-52). RAMP1
      enables CRL to form the CGRP-(8-37)-sensitive CGRP(1) receptor, which can also be
      activated by higher concentrations of AM. Here we review the available
      information on the pharmacological features and possible pathophysiological roles
      of the aforementioned AM receptors.

PMID- 15501535
TI  - Adrenomedullin in the treatment of pulmonary hypertension.
AB  - Adrenomedullin (AM) is a potent, long-lasting pulmonary vasodilator peptide.
      Plasma AM level is elevated in patients with primary pulmonary hypertension
      (PPH), and circulating AM is partially metabolized in the lungs. These findings
      suggest that AM plays an important role in the regulation of pulmonary vascular
      tone and vascular remodeling. We have demonstrated the effects of three types of
      AM delivery systems: intravenous administration, inhalation, and cell-based gene
      transfer. Despite endogenous production of AM, intravenously administered AM at a
      pharmacologic level decreased pulmonary vascular resistance in patients with PPH.
      Inhalation of AM improved hemodynamics with pulmonary selectivity and exercise
      capacity in patients with PPH. Cell-based AM gene transfer ameliorated pulmonary
      hypertension rats. These results suggest that additional administration of AM may
      be effective in patients with pulmonary hypertension. AM may be a promising
      endogenous peptide for the treatment of pulmonary hypertension.

PMID- 15501536
TI  - The pharmacology of CGRP-responsive receptors in cultured and transfected cells.
AB  - Historically, CGRP receptors have been classified as CGRP(1) or CGRP(2) subtypes,
      chiefly depending on their affinity for the antagonist CGRP(8-37). It has been
      shown that the complex between calcitonin receptor-like receptor (CRLR or CL) and
      receptor activity modifying protein (RAMP) 1 provides a molecular correlate for
      the CGRP(1) receptor; however, this does not explain the range of affinities seen
      for CGRP(8-37) in isolated tissues. It is suggested that these may largely be
      explained by a combination of methodological factors and CGRP-responsive
      receptors generated by CL and RAMP2 or RAMP3 and complexes of RAMPs with the
      calcitonin receptor.

PMID- 15501537
TI  - Biological importance of the peptides of the calcitonin family as revealed by
      disruption and transfer of corresponding genes.
AB  - The hormone calcitonin (CT) of thyroid C-cell origin, the neuropeptides alpha-
      and beta-calcitonin gene-related peptide (CGRP), the widely expressed hormone and
      tissue factor adrenomedullin (AM), and amylin (AMY) that is co-produced with
      insulin in pancreatic beta-cells, are structurally related peptides. They have in
      common six or seven amino acid ring structures, linked by disulfide bridges
      between cysteine residues, and amidated carboxyl termini that are both required
      for biological activity. The actions of the peptides in vivo have traditionally
      been studied after intravenous and intracerebroventricular administration. As a
      result, CT lowers serum calcium and reduces pain perception. alpha- and beta CGRP
      and AM are highly potent vasodilatory peptides. AMY inhibits food intake through
      its action in the area postrema of the brain. Physiological actions of the
      peptides summarized in the present review have been defined through gene knockout
      and overexpression strategies.

PMID- 15501538
TI  - Structure and biological properties of three calcitonin receptor-stimulating
      peptides, novel members of the calcitonin gene-related peptide family.
AB  - In this review, we describe the structure and biological properties of calcitonin
      receptor-stimulating peptide-1 (CRSP-1), CRSP-2 and CRSP-3, the novel members of
      the CGRP family. CRSP-1, which has been identified in the pig, cow, dog, and
      horse, is a specific ligand for the calcitonin (CT) receptor, and porcine CRSP-1
      elicits a 100-fold greater effect on a recombinant porcine CT receptor than
      porcine CT, although this peptide has high structural similarity with CGRP. CRSP
      1 is expressed and synthesized mainly in the central nervous system (CNS),
      pituitary and thyroid gland. In an in vivo experiment, bolus administration of
      CRSP-1 into rats reduced the plasma calcium concentration, but did not alter
      blood pressure, indicating its action as a CT receptor agonist in the peripheral
      circulation. In the CNS, CRSP-1 is also deduced to be an endogenous agonist for
      the CT receptor. CRSP-2 has been identified in the pig and dog, and CRSP-3 has
      been identified only in the pig. They are expressed and synthesized mainly in the
      CNS and thyroid gland. However, their endogenous molecular forms, receptors, and
      biological activity remain unidentified.

PMID- 15501539
TI  - A topological sub-structural approach for predicting human intestinal absorption
      of drugs.
AB  - The human intestinal absorption (HIA) of drugs was studied using a topological
      sub-structural approach (TOPS-MODE). The drugs were divided into three classes
      according to reported cutoff values for HIA. "Poor" absorption was defined as HIA
      < or =30%, "high" absorption as HIA > or =80%, whereas "moderate" absorption was
      defined between these two values (30% < HIA < 79%). Two linear discriminant
      analyses were carried out on a training set of 82 compounds. The percentages of
      correct classification, for both models, were 89.02%. The predictive power of the
      models were validated by three test: a leave-one-out cross validation procedure
      (88.9% and 87.9%), an external prediction set of 127 drugs (92.9% and 80.31%) and
      a test set of 109 oral drugs with bioavailability values reported (93.58% and
      91.84%). Finally, positive and negative sub-structural contributions to the HIA
      were identified and their possibilities in the lead generation and optimization
      process were evaluated.

PMID- 15501540
TI  - Umbelliferone aminoalkyl derivatives, a new class of squalene-hopene cyclase
      inhibitors.
AB  - The synthesis is described of several aminoalkyl derivatives of coumarin,
      obtained in good yields under microwave or high-intensity ultrasound irradiation.
      These compounds proved uniformly active as inhibitors of squalene-hopene cyclase
      (SHC) from Alicyclobacillus acidocaldarius. Their design stemmed from our recent
      finding that the umbelliferone nucleus acquires inhibitory properties towards SHC
      when functionalized with a suitable chain such as the omega-epoxyfarnesyl group.
      Under our experimental conditions the most active ones, such as 7-(4'
      allylmethylamino-but-2-ynyloxy)chromen-2-one (IC(50) 0.75 mM), approached the
      potency of anticholesteremic drug Ro 48-8071 (IC(50) 0.35 mM), an effective
      inhibitor of both squalene- and oxidosqualene-cyclases (OSC). Tests are in
      progress to determine their efficacy on different eukaryotic OSCs.

PMID- 15501541
TI  - Synthesis, anti-Trypanosoma cruzi activity and micelle interaction studies of
      bisguanylhydrazones analogous to pentamidine.
AB  - Three new bisguanylhydrazones analogous to pentamidine were synthesized, fully
      characterized and tested as anti-Trypanosoma cruzi candidates. Contrary to
      literature reports, that bicationic compounds are more active than monocationic
      compounds against Trypanosoma brucei, it was found that these bisguanylhydrazones
      are much less effective against T. cruzi than simple aromatic
      monoguanylhydrazones, thus suggesting different mechanism of action for both
      parasites. Spin-spin nuclear relaxation studies of the interaction of these
      compounds with SDS and CTAB micelles showed that only the most trypanocidal
      compound displays significant discrimination between anionic and cationic
      micelles.

PMID- 15501542
TI  - Synthesis of 4-hydroxycoumarin and 2,4-quinolinediol derivatives and evaluation
      of their effects on the viability of HepG2 cells and human hepatocytes culture.
AB  - We report here the synthesis of aromatic coumarins and aromatic alpha-quinolones
      which were evaluated in vitro for their protective potentialities against tert
      butyl hydroperoxide (t-BHP)-induced oxidative damage on human liver cell death,
      i.e., human hepatoma HepG2 cell line and human hepatocytes in primary culture. We
      found that the presence of a benzylidene at the 3-position or a heterocycle with
      N and S heteroatoms on the benzopyrone or quinolone system was essential for the
      protective effect of these compounds against t-BHP-induced decrease in viability
      of cells. We found also that a methoxy group on the aromatic ring systems
      decreased this potential. t-BHP-induced cytotoxicity in primary cultures of human
      hepatocytes could be therefore prevented by these compounds suggesting that they
      could display hepatoprotective effects in humans.

PMID- 15501543
TI  - Antiproliferative activity of new 1-aryl-4-amino-1H-pyrazolo[3,4-d]pyrimidine
      derivatives toward the human epidermoid carcinoma A431 cell line.
AB  - Synthesis and biological evaluation of a new class of 1-aryl-4-amino-1H
      pyrazolo[3,4-d]pyrimidine derivatives are reported. A preliminary cellular assay
      system using the tumor cell line A431 responding to epidermal growth factor (EGF)
      for its growth, shows that the new compounds are potent inhibitors of cell
      growth. The inhibition of tumor cell proliferation is not associated with
      blockage of EGF receptor (EGFR), but substantially due to the interference with
      the signalling pathway at the level of Src tyrosine kinase and at the level of
      the downstream effector signal mitogen activated protein kinases (MAPKs), ERK1-2.

PMID- 15501544
TI  - Synthesis, characterisation, activities, cell uptake and DNA binding of [[trans
      PtCl(NH3)2] [mu-(H2N(CH2)6NH2)] [trans-PdCl(NH3)2](NO3)Cl.
AB  - The dinuclear complex: [[trans-PtCl(NH(3))(2)] [mu-(H(2)N(CH(2))(6)NH(2))] [trans
      PdCl(NH(3))(2)](NO(3))Cl (code named DHD) has been synthesized and characterized.
      The activity against human cancer cell lines including ovarian: A2780,
      A2780(cisR), cell up take, level of binding with DNA and nature of interaction of
      the compound with pBR322 plasmid and salmon sperm DNAs have been determined. The
      compound is found to exhibit significant anticancer activity against ovarian
      cancer cell lines: A2780, A2780(cisR) and A2780(ZD0473R)--about two times as
      active as cisplatin against A2780 cell line, about five times as active as
      cisplatin against A2780(cisR) and A2780(ZD0473R) cell lines. The higher activity
      of DHD suggests that the compound is able to overcome multiple mechanisms of
      resistance operating in A2780(cisR) and A2780(ZD0473R) cell lines. DHD is
      believed to form a range of interstrand GG adducts with duplex DNA that induces
      global changes in the DNA conformation, unlike cisplatin and ZD0473 that form
      mainly intrastrand adducts that induces a local kink in a DNA strand. Increasing
      prevention of BamH1 digestion of form I and form II pBR322 plasmid DNA with the
      increase in concentration of DHD provides support to the idea that the
      interstrand binding of DHD with pBR322 plasmid DNA brings about global changes in
      DNA conformation.

PMID- 15501545
TI  - Homology modelling and binding site mapping of the human histamine H1 receptor.
AB  - Three-dimensional model of the human histamine H1 receptor was developed by
      homology modelling using the high resolution structure of bovine rhodopsin as
      template. Genetic algorithm based docking calculations were used to identify the
      role of several amino acids having an effect on agonist or antagonist binding.
      Binding mode analyses of mepyramine, desloratidine, loratidine and acrivastine
      allowed us to rationalise their binding affinity. Binding site mapping resulted
      in seven new potential aromatic interaction points (Tyr 108, Phe 184, Phe 190,
      Phe 199, Phe 424, Trp 428, Tyr 431), that took part in forming the lipophilic
      pocket of the antagonist binding cavity.

PMID- 15501546
TI  - Synthesis and antileishmanial profile of some novel terpenyl pyrimidines.
AB  - Some novel terpenyl pyrimidine derivatives 2(a-d) and 6(a-b) have been
      synthesised from alpha/beta-ionone keteneacetals 1 and 5. The terpenyl pyrimidine
      2e has been synthesised from beta-ionone 3 in two steps in quantitative yield.
      The pyrimidine derivatives were screened for in-vivo antilesihmanial activity.
      The compounds 2d, 2e, 6a and 6b showed promising in-vivo antileishmanial
      activity.

PMID- 15501547
TI  - Synthesis of pathogen inactivating nucleic acid intercalators.
AB  - A series of antiviral compounds consisting of an intercalating acridine derived
      part, a spacer region and a reactive EDTA-derived conjugate was synthesized in an
      easy sequence starting from 1,omega-alkyldiamines. As shown in model screenings,
      in the presence of ascorbic acid the Fe-complexes of these compounds reduced the
      phage-titer of MS2-phages by several logarithmic decades.

PMID- 15501548
TI  - Novel Mannich ketones of oxazolidinones as antibacterial agents.
AB  - A few Mannich ketones of piperazinyl oxazolidinone derivatives have been
      synthesized and their antibacterial activity in various Gram-positive organisms
      such as Bacillus subtilis, Staphylococcus aureus, Staphylococcus epidermidis and
      Enterococcus faecalis were evaluated by MIC determination. Compound 12 showed
      comparable activity (MIC) to linezolid and superior to eperezolid.

PMID- 15501550
TI  - Hepcidin and anaemia.
AB  - The anaemia of chronic disease (ACD) is a common haematologic syndrome
      characterized by hypoferraemia with adequate reticuloendothelial iron stores.
      Frequently, serum ferritin concentration in these patients is elevated. The
      pathogenesis of ACD involves abnormalities in red cell survival, the
      erythropoietic response to anaemia, and in iron metabolism. Hepcidin is an
      antibacterial protein produced in the liver which can be found in blood or urine,
      and which participates in host defense. Recent studies have demonstrated that
      hepcidin is a key regulator of iron balance in the intestinal mucosa, and that
      abnormalities in hepcidin gene expression are associated with clinical
      abnormalities in iron parameters and, in some cases, with anaemia. Hepcidin is an
      acute-phase reacting protein, and it has been suggested that hepcidin is the key
      mediator of ACD. Investigation of hepcidin production in either serum or urine
      demonstrates a strong correlation with serum ferritin concentration. Differences
      between the hepcidin concentrations observed in ACD (or syndromes resembling ACD)
      and those observed in iron deficiency may depend on the definition used for the
      anaemia syndrome. It seems very likely that hepcidin is a major contributor to
      iron abnormalities characteristic of ACD; whether it contributes to the
      pathogenesis of the syndrome in a broader sense remains to be determined by
      further investigation.

PMID- 15501549
TI  - Synthesis of prenylated benzaldehydes and their use in the synthesis of analogues
      of licochalcone A.
AB  - In this paper, a general applicable synthesis of prenylated aromatic compounds
      exemplified by prenylated benzaldehydes starting from readily available
      acetophenones is described. The synthesized benzaldehydes are used to prepare a
      number of novel analogues of Licochalcone A, a known antibacterial compound, and
      for the exploration of the pharmacophoric elements that are essential for the
      antibacterial activity. It is shown that the hydroxyl group in the A ring is
      essential for the activity and that the hydroxyl group in the B ring has no
      influence on the antibacterial effect of Licochalcone A. Furthermore, it is shown
      that the prenyl group at the position 5 of the B ring also has a dominating
      influence on the activity. This aliphatic group can be replaced by other
      lipophilic long chained substituents in order to maintain the activity.

PMID- 15501551
TI  - Wasted sheep and premature infants: the role of trace metals in hematopoiesis.
AB  - Trace element deficiencies and toxicities are not commonly encountered in
      clinical practice, particularly in regions where there is access to adequate
      nutrition and occupational exposures are regulated. However, specific clinical
      scenarios associated with trace metal deficiency and toxicity states do exist.
      Often, clues to the presence of these states may lie in the development of blood
      count abnormalities. The consultant haematologist is frequently involved in the
      care of these patients, and it is with this audience that this review is
      intended. This review will focus on the trace metals required for normal
      hematopoiesis including their function, metabolism, deficiency and toxicity
      states, and the clinical situations underlying these. As much of the information
      regarding trace metal disease states has arisen from veterinary medicine and from
      human case reports, these will be summarized and highlighted in this review.

PMID- 15501552
TI  - Dendritic cells in vaccination therapies of human malignant disease.
AB  - Dendritic cells (DC) are the most efficient antigen presenting cells in various
      in vitro systems and DC are now introduced to early clinical use. Tumor antigen
      loaded DC might potentially add therapeutic benefit with dendritic cell based
      vaccination. This review will focus on dendritic cell biology relevant to
      investigators who work in transitional research programs and will discuss the
      rationale of DC source, antigen loading and route of vaccination. An overview of
      published and on-going clinical trials in human malignant diseases will be
      provided forming the basis for a discussion of perspectives of dendritic cell
      vaccination in various human malignancies.

PMID- 15501553
TI  - "Off-license" use of recombinant activated factor VII.
AB  - Recombinant factor VIIa (rFVIIa) has been widely used in the treatment of
      bleeding episodes in haemophiliac patients with inhibitors. In haemostatic
      circles it has also been assessed in reversing oral anticoagulant therapy. Over
      the last few years, it has been used "off-label" in patients with uncontrolled
      bleeding due to haemostatic abnormalities due to trauma and/or massive blood
      loss, thrombocytopenia, platelet dysfunction or liver dysfunction. This review
      examines the proposed mechanism of action of rFVIIa in the context of current
      concepts of haemostasis and its pharmacological properties. The "off-license" use
      of rFVIIa is reviewed. The latter are reported mainly as case reports, case
      series. There is an overwhelming need for randomized controlled trials to assess
      rFVIIa's efficacy, dosing and safety in current "off-license" use.

PMID- 15501554
TI  - Unexplored issues and future directions in social phobia research.
AB  - There have been significant advances in recent years in the understanding and
      treatment of social phobia, which are summarised in this Special Issue. This
      paper outlines and describes some further priority areas for future research. It
      is suggested that social phobia should be investigated as a developmental
      condition, with special attention to the first two years of life; and subtypes of
      social phobia be further explored and their implication for treatment. Social
      phobia is often comorbid with other disorders and its relationship with these
      disorders warrants further investigation with respect to causality and treatment
      implications. Lastly, the investigation of social phobia within a health services
      research context is highlighted with the necessity of refining the design of
      clinical trials to establish the efficacy and effectiveness of current
      treatments.

PMID- 15501555
TI  - The etiology of social phobia: empirical evidence and an initial model.
AB  - Research into the etiology of social phobia has lagged far behind that of
      descriptive and maintaining factors. The current paper reviews data from a
      variety of sources that have some bearing on questions of the origins of social
      fears. Areas examined include genetic factors, temperament, childrearing,
      negative life events, and adverse social experiences. Epidemiological data are
      examined in detail and factors associated with social phobia such as cognitive
      distortions and social skills are also covered. The paper concludes with an
      initial model that draws together some of the current findings and aims to
      provide a platform for future research directions.

PMID- 15501556
TI  - The nature and expression of social phobia: toward a new classification.
AB  - Social phobia (social anxiety disorder) was officially recognized as a distinct
      clinical entity only with the publication of the DSM-III in 1980. Research on the
      psychopathology of this disorder has revealed a great degree of heterogeneity in
      its symptomatology. In order to acknowledge this heterogeneity, later versions of
      the nosological system introduced the generalized subtype of social phobia to
      describe individuals who fear most or all social situations. The empirical
      literature on the differences between the diagnostic subtypes has yielded
      inconsistent findings. Based on the recent emotion literature and concepts from
      evolutionary psychology, we discuss fearfulness, anxiousness, shyness, self
      consciousness, submissiveness, and anger as dimensions of social phobia. The
      empirical evidence for this classification system and its relationship to the
      diagnostic subtypes will be discussed.

PMID- 15501557
TI  - Information-processing bias in social phobia.
AB  - Social phobia is a persistent disorder that is unlikely to be maintained by
      avoidance alone. One reason for the enduring nature of social phobia may be the
      way individuals with the disorder process social information. It is important for
      those involved in social phobia to have an understanding of information
      processing biases, because it has the potential to guide psychological
      interventions. In this review of social phobia, probability and cost estimates of
      social situations are examined, interpretive biases are evaluated and findings
      relating to memory and negative imagery are also reviewed. The clinical
      implications of social-phobia-related information-processing biases are discussed
      and possible avenues for future research are outlined.

PMID- 15501558
TI  - Attention processes in the maintenance and treatment of social phobia:
      hypervigilance, avoidance and self-focused attention.
AB  - Four domains of evidence regarding the relationship between attention and social
      phobia are reviewed: (1) possible maintaining factor, (2) causal relationship,
      (3) specific relationship and (4) mediator of change during treatment. Two areas
      of research are covered and integrated: vigilance-avoidance of social threat
      stimuli and self-focused attention. There is empirical support for these
      processes as possible maintaining factors that are specific to patients and non
      clinical samples with high levels of social anxiety. There is reasonable evidence
      to promote the use of attentional strategies in the treatment of social phobia,
      although better controlled studies are required. We propose six overlapping
      mechanisms that could be responsible for change: reduced vigilance; reduced
      avoidance; reduced self-focused attention; mindfulness; increased attentional
      control; increased self-esteem.

PMID- 15501559
TI  - Interpersonal processes in social phobia.
AB  - Social phobia is a condition in which anxiety impairs the person's ability to
      relate to others. Here, we draw on concepts from interpersonal theory to examine
      the literature on the role of interpersonal processes in creating and maintaining
      this disorder. Studies that examine interpersonal interactions with significant
      others and strangers are reviewed. We next consider topics of particular
      relevance to relationship impairment, such as the effect of anxiety on cognitive
      processing of social information, and the social developmental pathways to social
      phobia. The impact of interpersonal factors on the process and outcome of
      cognitive-behavioral treatment is also discussed. Finally, we identify emerging
      themes in the research literature and consider directions for future work.
      Throughout the paper we highlight topics central to the interpersonal
      perspective, such as the self-perpetuating interpersonal cycle, interpersonal
      variability in social phobia, and the relational nature of self-related
      information.

PMID- 15501560
TI  - The treatment of social anxiety disorder.
AB  - We review the available treatments for social anxiety disorder, focusing
      primarily on psychotherapeutic interventions for adults, but also giving briefer
      summaries of pharmacological treatments and treatments for children and
      adolescents. The most well-researched psychosocial treatments for social anxiety
      disorder are cognitive-behavioral therapies (CBTs), and meta-analyses indicate
      that all forms of CBT appear likely to provide some benefit for adults. In
      addition, there are several pharmacological treatments with demonstrated
      efficacy, and cognitive-behavioral interventions have some demonstrated efficacy
      for children and adolescents. We outline a number of concerns regarding this
      literature, including the questions of what influences treatment response and
      what role combinations of CBT and medication might have. Clearly, although a
      number of treatments appear well-established in regard to their effects on social
      anxiety disorder, a number of opportunities for future research remain, including
      the search for predictors of who will benefit from which treatment.

PMID- 15501561
TI  - Generalized mean-field theory relating helix tilt in a bilayer to lipid disorder.
AB  - We present a generalized theory relating the helix tilt angle in a bilayer to
      lipid disorder. In doing so, we consider a theory performed earlier [Biophys.
      Chem., 86 (2000) 79] and generalize it within a nonextensive formalism. The
      generalized theory provides a method to compare the rotational barriers for
      different helices in lipid bilayers, accounting for long-range interactions via a
      parameter which is called "entropic index". The results obtained could lead to
      point out future experiments which might shed light on lipid-protein
      interactions.

PMID- 15501562
TI  - The structure of DNA-DLPC-cationic gemini surfactant aggregates: a small angle
      synchrotron X-ray diffraction study.
AB  - The structure of aggregates formed by interaction of DNA with unilamellar
      dilauroylphosphatidylcholine (DLPC) vesicles (DNA:DLPC=1:1 base/mol) in the
      presence of gemini surfactant butane-1,4-diyl-bis(dodecyldimethylammonium
      bromide) (C12GS) was investigated using synchrotron small angle X-ray
      diffraction. In the concentration range C12GS+:DLPC< or =1 mol/mol, a condensed
      lamellar Lalphac phase was found with a repeat period of lipid bilayer stacking
      in the range d approximately 5.70-6.53 nm and the DNA interhelical distance
      d(DNA) approximately 3.52-3.99 nm, depending on the concentration of C12GS. At
      molar ratio C12GS+:DLPC> or =0.35:1, the diffractograms have shown the presence
      of a second lamellar phase with the repeat period d approximately 5.31 nm which
      slightly decreases with increasing concentration of C12GS+. The increasing
      fraction of this phase in the aggregates with increasing concentration of C12GS
      supports the association of this phase with microscopic domains enriched by
      surfactant molecules. The temperature behaviour of aggregates was investigated in
      the range 25-60 degrees C and the transversal thermal expansivities of the
      observed phases were determined.

PMID- 15501563
TI  - Effects of a hairpin polyamide on DNA melting: comparison with distamycin and
      Hoechst 33258.
AB  - We have used DNase I footprinting and fluorescence melting studies to study the
      interaction of the hairpin polyamide Im-Py-Py-Py-(R)H2Ngamma-Im-Py-Py-Py-beta-Dp
      with its preferred binding sites (5'-WGWWCW; W=A or T) and other sequences. DNase
      I footprinting confirmed that the ligand binds to the sequence AGAACA at
      nanomolar concentrations and that changing the terminal A to G causes a dramatic
      decrease in affinity, while there was no interaction with the reverse sequence
      WCWWGW. Fluorescence melting studies with 11-mer duplexes showed that the
      polyamide had very different effects on the forward (TGWWCT) and reverse (TCTAGT)
      sequences. At low concentrations, the polyamide produced biphasic melting curves
      with TGATCT, TGTACT and TGAACT, suggesting a strong interaction. In contrast, the
      melting profiles with TCTAGT were always monophasic and showed much smaller
      concentration dependent changes in Tm. The polyamide also showed weak binding to
      the sequence TGATCT when one of the central AT pairs was replaced with an AC
      mismatch. These melting profiles were compared with those produced by the AT
      selective minor groove binding agents distamycin and Hoechst 33258 at the same
      sites and at similar sequences containing A5 and (AT)3, which are expected to
      bind distamycin in the 1:1 and 2:1 modes, respectively. These ligands produced
      simple monophasic melting curves in which the Tm steadily increased as the ligand
      concentration was raised.

PMID- 15501564
TI  - Characteristics of structure, composition, mass spectra, and iron release from
      the ferritin of shark liver (Sphyrna zygaena).
AB  - The ferritin consists of a protein shell constructed of 24 subunits and an iron
      core. The liver ferritin of Sphyrna zygaena (SZLF) purified by column
      chromatography is a protein composed of eight ferritins containing varying iron
      numbers ranging from 400+/-20 Fe3+/SZLF to 1890+/-20 Fe3+/SZLF within the protein
      shell. Nature SZLF (SZLFN) consisting of holoSZLF and SZLF with unsaturated iron
      (SZLFUI) to have been purified with polyacrylamide gel electrophoresis (PAGE)
      exhibited five ferritin bands with different pI values ranging from 4.0 to 7.0 in
      the gel slab of isoelectric focusing (IEF). HoloSZLF purified by PAGE (SZLFE) not
      only had 1890+/-20 Fe3+/SZLFE but also showed an identical size of iron core
      observed by transmission electron microscopy (TEM). Molecular weight of
      approximately 21 kDa for SZLFE subunit was determined by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE). Four peaks of molecular ions at
      mass/charge (m/z) ratios of 10611.07, 21066.52, 41993.16, and 63555.64 that come
      from the SZLFE were determined by matrix-assisted laser desorption
      ionization/time-of-flight mass spectrometry (MALDI-TOF MS), which were identified
      as molecular ions of the ferritin subunit (M+) and its polymers, namely, [M]2+,
      [M]+, [2M]+, and [3M]+, respectively. Both SZLFE and a crude extract from shark
      liver of S. zygaena showed similar kinetic characteristics of complete iron
      release with biphasic behavior. In addition, a combined technique of visible
      spectrometry and column chromatography was used for studying ratio of phosphate
      to Fe3+ within the SZLFE core. Interestingly, this ratio maintained invariable
      even after the iron release, which differed from that of other mammal ferritins.

PMID- 15501565
TI  - Effect of pH on the conformation of gellan chains in aqueous systems.
AB  - The optical rotation and fluorescence anisotropy for gellan aqueous systems were
      measured at pH 4, 7, and 10 to elucidate the effect of pH on the conformation of
      gellan chains. The optical rotation study suggests that pH affects the
      conformation of helical gellan chains and their aggregation behavior but the coil
      helix transition temperature. By comparing the chain mobility estimated from the
      fluorescence anisotropy between different pH conditions, it has been revealed
      that the degree of expansion of random-coiled gellan chains varies with pH. These
      results indicate that the effect of pH is explained by the change in the anionic
      nature of gellan chains rather than in the shielding effect of hydrogen ions
      surrounding gellan chains as a cation species.

PMID- 15501566
TI  - An electrochemical study of hemoglobin in water-glycerol solutions.
AB  - The effect the composition of a water-glycerol mixture has on the electrochemical
      properties of hemoglobin (Hb) is studied. With the increased glycerol
      concentrations, the peak-to-peak separation of hemoglobin is found to increase
      from approximately 40 to 200 mV, with the apparent standard potential of
      hemoglobin negatively shifted, which demonstrate that the electron-transfer
      activity of hemoglobin will decrease at relatively high glycerol concentrations
      and the oxidized state of hemoglobin will be more stable with the increasing
      glycerol concentrations. Meanwhile, the electrocatalytic activity of hemoglobin
      to hydrogen peroxide, as well as the binding of ligands or effectors to
      hemoglobin in the presence of glycerol, are also been investigated. Our studies
      indicate that glycerol will decrease the electrocatalytic activity of hemoglobin,
      while have little effect on the microenvironment around the heme site.

PMID- 15501567
TI  - Experiment-guided thermodynamic simulations on reversible two-state proteins:
      implications for protein thermostability.
AB  - Here, we perform protein thermodynamic simulations within a set of boundary
      conditions, effectively blanketing the experimental data. The thermodynamic
      parameters, melting temperature (TG), enthalpy change at the melting temperature
      (DeltaHG) and heat capacity change (DeltaCp) were systematically varied over the
      experimentally observed ranges for small single domain reversible two-state
      proteins. Parameter sets that satisfy the Gibbs-Helmholtz equation and yield a
      temperature of maximal stability (TS) around room temperature were selected. The
      results were divided into three categories by arbitrarily chosen TG ranges. The
      TG ranges in these categories correspond to typical values of the melting
      temperatures observed for the majority of the proteins from mesophilic,
      thermophilic and hyperthermophilic organisms. As expected, DeltaCp values tend to
      be high in mesophiles and low in hyperthermophiles. An increase in TG is
      accompanied by an up-shift and broadening of the protein stability curves,
      however, with a large scatter. Furthermore, the simulations reveal that the
      average DeltaHG increases with TG up to approximately 360 K and becomes constant
      thereafter. DeltaCp decreases with TG with different rates before and after
      approximately 360 K. This provides further justification for the separate
      grouping of proteins into thermophiles and hyperthermophiles to assess their
      thermodynamic differences. This analysis of the Gibbs-Helmholtz equation has
      allowed us to study the interdependence of the thermodynamic parameters TG,
      DeltaHG and DeltaCp and their derivatives in a more rigorous way than possible by
      the limited experimental protein thermodynamics data available in the literature.
      The results provide new insights into protein thermostability and suggest
      potential strategies for its manipulation.

PMID- 15501568
TI  - Absorption and fluorescence spectra of ring-substituted indole-3-acetic acids.
AB  - The absorption and fluorescence spectra of indole-3-acetic acid (1), a plant
      growth regulator (auxin) and experimental cancer therapeutic, 29 ring-substituted
      derivatives and the 7-aza analogue (1H-pyrrolo[2,3b]pyridine-3-acetic acid) are
      compared. Two to four absorbance maxima in the 260-310-nm range are interpreted
      as overlapping vibronic lines of the 1La<--1A and 1Lb<--1A transitions. Two
      further maxima in the 200-230-nm region are assigned to the 1Ba<--1A and 1Bb<--1A
      transitions. 4- and 7-Fluoroindole-3-acetic acid exhibit blue shifts with respect
      to 1, most other derivatives show red shifts. All indole-3-acetic acids studied,
      with the exception of chloro-, bromo- and 4- or 7-fluoro-derivatives, fluoresce
      at 345-370 nm when excited at 275-280 nm. 7-Azaindole-3-acetic acid emits at 411
      nm. The fluorescence quantum yield of 6-fluoroindole-3-acetic acid significantly
      exceeds that of 1 (0.3); the other derivatives have lower quantum yields. The
      plant-growth promoting activity of the ring-substituted indole-3-acetic acids
      studied correlates with the position of the 1Bb<--1A transition band.

PMID- 15501569
TI  - Interaction of echinomycin with guanine: electrochemistry and spectroscopy
      studies.
AB  - The interaction of antitumor antibiotic, echinomycin (Echi) with guanine (Gua)
      was thoroughly investigated by adsorptive transfer stripping cyclic voltammetry,
      ultraviolet and visible adsorption spectra (UV/Vis) and Fourier-transform
      infrared spectroscopy (FTIR). Electrochemistry provided a simple tool for
      verifying the occurrence of interaction between Echi and Gua. Echi could be
      accumulated from the solution and give well-defined electrochemical signals in
      0.1 M phosphate buffer solution (pH 7.0) only when Gua was present on the surface
      of the electrochemically pretreated glass carbon electrode (GCE), suggesting a
      strong binding of Echi to Gua. All the acquired spectral data showed that a new
      adduct between Echi and Gua was formed, and two pairs of adjacent intermolecular
      hydrogen bonds between the Ala backbone atoms in Echi and Gua (Ala-NH to Gua-N3
      and Gua-NH2 to Ala-CO) played a dominating role in the interaction.
      Electrochemistry coupled with spectroscopy techniques could provide a relatively
      easy way to obtain useful insights into the molecular mechanism of drug-DNA
      interactions, which should be important in the development of new anticancer
      drugs with specific base recognition.

PMID- 15501570
TI  - Activation of ryanodine receptors in the nuclear envelope alters the conformation
      of the nuclear pore complex.
AB  - Nuclear pore complexes (NPCs) are supramolecular protein pores that traverse the
      nuclear envelope and form the only known direct route of transport between the
      cytoplasmic and nuclear spaces. Detailed studies have identified both active and
      passive mechanisms of transport through the NPC and structural studies have
      revealed its three-dimensional architecture. Under certain conditions, structural
      studies have found evidence for a mass in the central pore of the NPC whose
      identity remains unclear. Some studies suggest this mass represents cargo caught
      in transit, while others suggest it is an integral component of the NPC, the
      position of which is sensitive to sample conditions. Regardless of its identity,
      previous studies have shown that the central mass location within the NPC pore is
      influenced by the presence of calcium in the cisternal spaces of the nuclear
      membrane. Specific depletion of these calcium stores through inositol 1,4,5
      trisphosphate (IP(3)) receptor activation leads to the apparent displacement of
      the central mass towards both the cytoplasmic and nucleoplasmic sides of the NPC.
      Whether the central mass is cargo or a NPC component, these observations may
      offer interesting insights linking transport and calcium signaling pathways.
      Here, we show that ryanodine (Ry) receptors are also present in the nuclear
      envelope of Xenopus laevis oocytes, and their specific activation can affect the
      conformational state of the NPC. Although previously undetected, Western blot
      analysis of isolated oocyte nuclei reveals the presence of Ry receptors in the
      nuclear envelope, albeit in low abundance. Extensive atomic force microscopy
      (AFM) studies at the single pore level of isolated, fixed nuclei reveal changes
      in the NPC conformational state following treatments that stimulate Ry receptor
      activity. At resting calcium levels ( approximately 200 nM Ca(2+)), the central
      mass within the lumen of the NPC is recessed 5.3 nm below the cytoplasmic rim of
      the NPC. Following treatment with 10 nM ryanodine, the central mass displaces
      towards the cytoplasmic face occupying a new position only 2.9 nm below the
      cytoplasmic rim. Interestingly, at high ryanodine concentrations (20 microM),
      which are reported to deactivate Ry receptors, the central mass is observed to
      return to the recessed position, 5.4 nm below the cytoplasmic rim. Treatments
      with caffeine also lead to large changes in the NPC conformation, confirming the
      link to specific activation of Ry receptors. These observations are consistent
      with a new mechanism of NPC regulation in which specific activation of Ry
      receptors located in the nuclear envelope can modulate cisternal calcium levels,
      leading to changes in the NPC conformation. Together with previous studies, it
      now appears that both IP(3) and Ry receptors are present in the nuclear envelope
      of Xenopus oocytes and are capable, through activation, of indirectly influencing
      the conformational state of the NPC.

PMID- 15501571
TI  - Fluorometric investigation of interaction of 3-acetyl-4-oxo-6,7-dihydro-12H
      indolo-[2,3-a] quinolizine with bovine serum albumin.
AB  - Interaction of 3-acetyl-4-oxo-6,7-dihydro-12H indolo-[2,3-a] quinolizine (AODIQ)
      with a model transport protein, bovine serum albumin (BSA), has been studied
      using steady state fluorescence and fluorescence anisotropy experiments. Upon
      binding with BSA, the charge transfer (CT) fluorescence exhibits appreciable
      hypsochromic shift along with an enhancement in the fluorescence intensity.
      Gradual addition of BSA leads to the marked increase in the fluorescence
      anisotropy (r). From the high value of fluorescence anisotropy (r=0.30) it is
      argued that the probe molecule is located in motionally restricted environment of
      the protein. Addition of urea to the protein bound AODIQ leads to the decrease in
      fluorescence intensity as well as fluorescence anisotropy (r) indicating the
      release of AODIQ molecule to the aqueous buffer medium, thus supporting the idea
      that the protein, in its native form, binds with the probe. The binding constant
      and free energy change (DeltaG(0)) for the interaction of AODIQ with BSA have
      been evaluated from relevant fluorescence data. Polarity of the microenvironment
      has been determined from a comparison of the variation of fluorescence property
      of the probe in dioxane-water mixture with varying composition.

PMID- 15501572
TI  - In vitro biochemical and thermodynamic characterization of nucleocapsid protein
      of SARS.
AB  - The major biochemical and thermodynamic features of nucelocapsid protein of SARS
      coronavirus (SARS_NP) were characterized by use of non-denatured gel
      electrophoresis, size-exclusion chromatographic and surface plasmon resonance
      (SPR) techniques. The results showed that SARS_NP existed in vitro as oligomer,
      more probably dimer, as the basic functional unit. This protein shows its maximum
      conformational stability near pH 9.0, and it seems that its oligomer dissociation
      and protein unfolding occur simultaneously. Thermal-induced unfolding for SARS_NP
      was totally irreversible. Both the thermal and chemical denaturant-induced
      denaturation analyses showed that oligomeric SARS_NP unfolds and refolds through
      a two-state model, and the electrostatic interactions among the charge groups of
      SARS_NP made a significant contribution to its conformational stability.

PMID- 15501573
TI  - Combing DNA on CTAB-coated surfaces.
AB  - A fluorescence microscope (FM) coupled with an intensified charge-coupled device
      (ICCD) camera was used to investigate the combing of DNA on cetyltrimethyl
      ammonium bromide (CTAB)-coated glass surfaces. DNA molecules can be combed
      uniform and straight on CTAB-coated surfaces. Different combing characteristics
      at different pH values were found. At lower pH (ca. 5.5), DNA molecules were
      stretched 30% longer than the unextended and DNA extremities bound with CTAB
      coated surfaces via hydrophobic interaction. At high pH values (e.g., 6.4 and
      6.5), DNA molecules were extended about 10% longer and DNA extremities bound with
      CTAB-coated surfaces via electrostatic attraction. At pH 6.0, DNA molecules could
      be extended 30% longer on 0.2-mM CTAB-coated surfaces. CTAB cationic surfactant
      has both a hydrophobic motif and a positively charged group. So, CTAB-coated
      surfaces can bind DNA extremities via hydrophobic effect or electrostatic
      attraction at different pH values. It was also found that combing of DNA on CTAB
      coated surfaces is reversible. The number of DNA base pairs binding to CTAB
      coated surfaces was calculated.

PMID- 15501574
TI  - Thermal stability of wild type and disulfide bridge containing mutant of poplar
      plastocyanin.
AB  - A comparative study of the thermal stability of wild type poplar plastocyanin and
      of a mutant form containing a disulfide bridge between residues 21 and 25 was
      performed using differential scanning calorimetry and optical spectroscopic
      techniques. For wild type plastocyanin the transition temperature, determined
      from the calorimetric profiles, is 62.7 degrees C at the scan rate of 60 degrees
      C/h, whereas for the mutant it is reduced to 58.0 degrees C. In both cases, the
      endothermic peak is followed by an exothermic one at higher temperatures. The
      unfolding process monitored by optical absorption at 596 nm also reveals a
      reduced thermal stability of the mutated plastocyanin compared to the wild type
      protein, with transition temperatures of 54.8 and 58.0 degrees C, respectively.
      For both proteins, the denaturation process was found to be irreversible and
      dependent on the scan rate preventing the thermodynamic analysis of the unfolding
      process. In parallel, small conformational changes between wild type and mutant
      plastocyanin emerge from fluorescence spectroscopy measurements. Here, a
      difference in the interaction of the two proteins between the microenvironment
      surrounding the fluorophores and the solvent was proposed. The destabilization
      observed in the disulfide containing mutant of plastocyanin suggests that the
      double mutation, Ile21Cys and Glu25Cys, introduces strain into the protein which
      offsets the stabilizing effect expected from the formation of a covalent
      crosslink.

PMID- 15501575
TI  - Kosmotropes and chaotropes: modelling preferential exclusion, binding and
      aggregate stability.
AB  - Kosmotropic cosolvents added to an aqueous solution promote the aggregation of
      hydrophobic solute particles, while chaotropic cosolvents act to destabilise such
      aggregates. We discuss the mechanism for these phenomena within an adapted
      version of the two-state Muller-Lee-Graziano model for water, which provides a
      complete description of the ternary water/cosolvent/solute system for small
      solute particles. This model contains the dominant effect of a kosmotropic
      substance, which is to enhance the formation of water structure. The consequent
      preferential exclusion both of cosolvent molecules from the solvation shell of
      hydrophobic particles and of these particles from the solution leads to a
      stabilisation of aggregates. By contrast, chaotropic substances disrupt the
      formation of water structure, are themselves preferentially excluded from the
      solution, and thereby contribute to solvation of hydrophobic particles. We use
      Monte Carlo simulations to demonstrate at the molecular level the preferential
      exclusion or binding of cosolvent molecules in the solvation shell of hydrophobic
      particles, and the consequent enhancement or suppression of aggregate formation.
      We illustrate the influence of structure-changing cosolvents on effective
      hydrophobic interactions by modelling qualitatively the kosmotropic effect of
      sodium chloride and the chaotropic effect of urea.

PMID- 15501576
TI  - The binding of zinc (II) to a double-stranded oligodeoxyribonucleotide. A
      voltammetric study.
AB  - Binding of zinc to a 19 mer double-stranded oligodeoxyribonucleotide was
      investigated by anodic stripping voltammetry and cyclic voltammetry in order to
      understand the roles of zinc in DNA cleavage catalyzed by mung bean nuclease.
      These methods rely on the direct monitoring of zinc oxidation current in the
      absence and in the presence of the oligo. Zinc titration curves with the ds
      oligodeoxyribonucleotide were obtained in concentrations ranging from 3.62 x 10(
      9) to 3.62 x 10(-8) M and 4.06 x 10(-10) to 5.25 x 10(-9) M. The acquired data
      were used to determine the dissociation constant, stoichiometry and zinc binding
      sites of the complex and to understand the specific changes of ds
      oligodeoxyribonucleotide secondary structure by zinc binding. The oxidation
      reduction process of zinc was also investigated by cyclic voltammetry through I
      (oxidation current) versus v(1/2) (square root of scan rate) curves in the
      absence and in the presence of the double-stranded oligodeoxyribonucleotide.

PMID- 15501577
TI  - Investigation of double stranded DNA damage induced by quercetin-copper(II) using
      piezoelectric quartz crystal impedance technique and potentiometric stripping
      analysis.
AB  - DNA damage by quercetin-Cu(2+) was monitored in real time by piezoelectric quartz
      crystal impedance (PQCI) technique. In the PQCI analysis, the frequency change
      was caused mainly by the changes in density-viscosity of DNA solution in the
      damage course. The influences of DNA, Cu(2+), and quercetin concentrations on the
      motional resistance change (DeltaR(m)) were investigated in detail. The results
      showed that quercetin exhibited pro-oxidative damage at lower concentrations
      while anti-oxidative protection at higher concentrations, and DeltaR(m) exhibited
      a linear relationship in the DNA concentration range from 200 to 1600 microg/ml.
      Potentiometric stripping analysis (PSA) was also used to observe the
      electrochemical behavior of damaged DNA. From PSA, a new peak at 0.84 V and a
      higher peak at 1.06 V were discovered, which suggested that more purines were
      exposed to the electrode surface during the damage course. In agarose-gel
      electrophoresis, catalase and biquinoline were found to effectively inhibit DNA
      damage, therefore, a possible damage mechanism was proposed.

PMID- 15501578
TI  - Sequence-dependent DNA torsional rigidity: a tetranucleotide code.
AB  - Using fluorescence polarization anisotropy (FPA), we measured the torsional
      constant of various DNA oligomers in different sequences and calculated the value
      for each of the 136 unique tetranucleotides. From these values, we obtained a
      "rigidity profile" for every double-stranded DNA sequence. We tested the code in
      the analysis of DNA sequences able to form nucleosomes. More than 50% of the
      sequences studied showed a common 20 and/or 30 bp modulation of the torsional
      constant. Many other profiles of rigidity were observed in the remaining
      sequences and this variety in torsional constant modulation may be related to
      functional differences between nucleosomes.

PMID- 15501579
TI  - Insulin-like growth factor-II stimulates steroidogenesis in cultured bovine
      thecal cells.
AB  - The objective of the present study was to determine the effects of insulin-like
      growth factor-II (IGF-II) on luteinizing hormone (LH)-induced progesterone and
      androstenedione production by bovine thecal cells and compare it to that of
      insulin and IGF-I. Cells from large (>7.9 mm) bovine follicles were collected and
      cultured for 2 days in the presence of 10% fetal calf serum. Then cells were
      cultured for an additional 1 or 2 days in serum-free medium with various doses of
      recombinant human IGF-II, bovine LH (30 ng/ml), IGF-I, and(or) insulin. Cell
      numbers were determined at the end of treatments via Coulter counting and used to
      correct steroid production data. In the presence of LH, 1-day treatment with 3
      300 ng/ml of IGF-II had no significant effect on progesterone or androstenedione
      production, whereas 2-day treatment with 30, 100 and 300 ng/ml of IGF-II
      increased (P < 0.05) both progesterone and androstenedione production by 2-3
      fold. The estimated effective dose of IGF-II stimulating 50% of the maximal
      steroidogenic response was calculated to be 25 ng/ml. In the absence of LH, 2-day
      treatment of IGF-I or -II had no effect on thecal androstenedione production but
      increased (P < 0.05) thecal progesterone production. In the presence of LH, 100
      ng/ml of IGF-I increased progesterone and androstenedione production to a greater
      degree than did 100 ng/ml of IGF-II. Maximal effects of IGF-I and insulin on
      thecal steroidogenesis were similar and were not additive. Anti-IGF type I
      receptor antibodies attenuated (P < 0.05) the stimulatory effect of both IGF-I
      and IGF-II on thecal cell steroidogenesis. Use of radioligand assays demonstrated
      that specific receptors for (125)I-IGF-II existed in thecal cells with a 25
      ng/well of IGF-II causing 50% inhibition of binding. IGF-I cross-reactivity with
      (125)I-IGF-II receptors averaged 3% whereas cross-reactivity of IGF-II with
      (125)I-IGF-I receptors averaged 114%. These results indicate that the stimulatory
      effects of IGF-II on thecal cell steroidogenesis is mediated by IGF type I
      receptors and thus IGF-II, like IGF-I, may play a significant role in thecal cell
      steroidogenesis during follicular development.

PMID- 15501580
TI  - Selective estrogen receptor modulators prevent neointima formation after vascular
      injury.
AB  - Exploitation of estrogen's vasculoprotective properties in drug design is
      difficult due to its adverse effects on endometrium and breast. Selective
      estrogen receptor modulators (SERM) act as estrogen agonists in some tissues but
      are anti-estrogenic in others. We investigate here whether tamoxifen, raloxifene,
      and two novel SERMs, ospemifene and fispemifene, preserve estrogen's beneficial
      effects on the ovariectomized rat vascular wall, and correlate their effects with
      natural estrogen (17beta-E2) and a pure anti-estrogen ICI 182,780. All compounds
      dose-dependently (0.0025-25 mg/kg/day) inhibited neointimal thickening at 7 days
      after aorta denudation injury. At 28 days, tamoxifen and ospemifene (2.5
      mg/kg/day) reduced intimal nuclei number and intimal area equal to 17beta-E2,
      while raloxifene and fispemifene had no effect. Replacing the drug at 14 days
      with vehicle did not induce any rebound effect at 28 days, and furthermore,
      resulted in a smaller neointima with raloxifene and fispemifene. 17beta-E2 and
      the SERMs also significantly enhanced reendothelialization. All compounds
      inhibited replication and all but fispemifene inhibited migration of vascular SMC
      and cells from cultured aortic explants in vitro. Finally, only 17beta-E2
      increased the weight of the uterus above that of normal rats. Interestingly, ICI
      182,780 also weakly inhibited neointima formation and SMC proliferation at 7
      days, suggesting that non-estrogen receptor mediated effects may have also played
      a role. In conclusion, SERMs have beneficial estrogen agonist effects in the
      injured vascular wall through their regulation of vascular SMC function and
      reendothelialization. Early intervention is of particular importance in
      preventing the injury-response.

PMID- 15501581
TI  - Quantitative proteome analysis in benign thyroid nodular disease using the
      fluorescent ruthenium II tris(bathophenanthroline disulfonate) stain.
AB  - Thyroid tumorigenesis involves qualitative and quantitative changes in protein
      expression, which can be comprehensively studied by proteome analysis. However,
      one of the technical bottlenecks of proteomics remains a reliable, sensitive and
      inexpensive method for quantification of differentially expressed proteins. This
      is due to the limited linear range of most available protein stains, i.e. silver
      and Coomassie blue, and high costs of commercially available fluorescent stains.
      In this paper we describe our experience with a lab-made ruthenium based
      fluorescent stain (ruthenium II tris(bathophenanthroline disulfonate) (RuBPs)) to
      perform proteome analysis of nodular thyroid disease. We first compared the
      properties of RuBPs with two highly sensitive protein stains: (1) silver staining
      and (2) the commercially available fluorescent dye Sypro Ruby. We show that in
      addition to its highly sensitive staining capabilities similar to Sypro Ruby and
      silver (2 ng), RuBPs offers several advantages such as a broad dynamic range
      (similar to Sypro Ruby and 500 times broader than the dynamic range of silver
      stain), low costs ( 0.03 per gel) and excellent compatibility with mass
      spectrometry. We then applied the inexpensive RuBPs stain to 2D gels (pH 4-7) of
      four benign thyroid nodules and normal thyroid tissue. We were able to detect
      approximately 1800 protein spots/gel in our thyroid samples. Quantitative changes
      in protein expression levels of at least 20-42 proteins were noted in the benign
      nodules compared with the normal thyroid tissue of the same patient.
      Differentially expressed spots were further characterised by nano-LC-FTICR and
      MALDI-TOF mass spectrometry. In summary we demonstrate, that the novel
      fluorescent ruthenium II tris(bathophenanthroline disulfonate) stain is a highly
      sensitive, reliable and inexpensive tool for quantitative proteome analysis in
      thyroid nodular disease.

PMID- 15501582
TI  - Expression of the GATA-4 and GATA-6 transcription factors in the fetal rat gonad
      and in the ovary during postnatal development and pregnancy.
AB  - Immunohistochemical studies were undertaken to determine the distribution of GATA
      4 and GATA-6 in rat fetal gonad and the postnatal ovary during development and
      pregnancy. In the undifferentiated gonad, GATA-4 was expressed in the somatic
      cells of both sexes. After differentiation of the ovary and testis, GATA-4
      expression continued in both ovarian and testicular somatic cells; whereas, GATA
      6 was expressed in both somatic and germ cells. In the ovary of postnatal rats,
      granulosa and thecal cells of healthy follicles expressed both GATA factors. In
      the adult rat, GATA-4 expression was lower in corpora lutea as compared to
      follicles; whereas, GATA-6 was strongly expressed in both structures. GATA-4
      expression was greater in functional corpora lutea than regressing corpora lutea.
      GATA-6 was expressed in both functional and regressing corpora lutea. In all
      postnatal ovaries, the expression of P450scc localized with tissue expressing
      GATA-4 and/or GATA-6, but GATA expression also occurred in P450scc negative
      cells.

PMID- 15501583
TI  - Cloning and tissue-specific localization of cricket-type allatostatins from
      Gryllus bimaculatus.
AB  - Cricket- or B-type allatostatins [W(X(6))W-amides] inhibit the biosynthesis of
      juvenile hormones in vitro in crickets. Peptides of this family are present also
      in other insects where they may bare different functions. Here we report the
      identification of a partial sequence of the B-type preproallatostatin from
      Gryllus bimaculatus. By PCR screening of a random primer cDNA library and by
      RACE, a 535bp 3'cDNA sequence was obtained which encodes a putative translation
      product of 85 amino acids, containing three copies of Grybi-AST B1 and one copy
      each of Grybi-AST B2, Grybi-AST B3, and Grybi-AST B6. The last represents a novel
      member of this peptide family. By means of one-step RT-PCR, RNA dot blot, and RT
      in situ PCR analyses the mRNA expression of the gene in the central nervous
      system and the digestive tract of female adult crickets was demonstrated. The
      results confirm that the B-type allatostatins of G. bimaculatus are brain-gut
      peptides.

PMID- 15501585
TI  - Disruption of reconsolidation but not consolidation of auditory fear conditioning
      by noradrenergic blockade in the amygdala.
AB  - Consolidation is a process through which labile memories are made persistent
      [Science 287 (2000) 248]; [Annu Rev Psychol 55 (2004) 51]. When retrieved, a
      consolidated memory is rendered labile again and undergoes reconsolidation [Learn
      Mem 7 (2000) 73]; [Trends Neurosci 26 (2003) 65]). Reconsolidation thus offers
      the opportunity to manipulate memory after it is formed, and may therefore
      provide a means of treating intrusive memories associated with post-traumatic
      stress disorder (PTSD). Reconsolidation is most usually studied using protein
      synthesis inhibitors, which is not practical in humans. However, the beta
      adrenergic receptor antagonist propranolol impairs consolidation of declarative
      memory in humans [Science 287 (2000) 248]; [Nature 371 (1994) 702] and
      consolidation and reconsolidation of inhibitory avoidance learning in rats [Brain
      Res 368 (1986) 125]; [J Neurosci 19 (1999) 6623]. Here, we show that systemic or
      intra-amygdala infused propranolol blocks reconsolidation but not consolidation.
      If the effects on reconsolidation are verified in humans, the results would
      suggest the possibility that propranolol after memory retrieval might be an
      effective way of treatment of intrusive memories in PTSD. That the systemic
      effects of propranolol on reconsolidation are achieved via an action in the
      amygdala is especially important in light of the fact that PTSD involves
      alterations in the amygdala [Arch Gen Psychiatry 53 (1996) 380].

PMID- 15501584
TI  - Ligand-independent and agonist-mediated degradation of estrogen receptor-alpha in
      breast carcinoma cells: evidence for distinct degradative pathways.
AB  - Molecular chaperones and co-chaperones, such as heat-shock proteins (Hsp's), play
      a pivotal role in the adequate folding and the stability of steroid hormone
      receptors. As shown by immunofluorescence staining and immunoblot analysis, the
      Hsp90 inhibitor radicicol induced a rapid (within hours) depletion of estrogen
      receptor-alpha (ER) in MCF-7 and IBEP-2 breast carcinoma cells. Inhibition of
      proteasomes (MG-132, LLnL) or of protein synthesis (cycloheximide), which both
      suppressed E(2)-induced downregulation of ER, failed to modify ER degradation
      caused by radicicol. On the other hand, partial antiestrogens, such as
      hydroxytamoxifen (a triphenylethylene) and LY 117,018 (a benzothiophene)
      stabilized ER, making it immune to radicicol-induced degradation. Furthermore,
      radicicol did not interfere with ER upregulation induced by hydroxytamoxifen.
      Thus, the current study points to possible variation in the mechanism/pathway of
      ER breakdown. Besides, the protective effect of partial antiestrogens suggests
      that ER stability is only compromized by Hsp90 disruption when the receptor is in
      its native, unliganded form.

PMID- 15501586
TI  - N-methyl-D-aspartate receptor-independent long-term depression and depotentiation
      in the sensorimotor cortex of the freely moving rat.
AB  - Bidirectional modifications in synaptic efficacy are central components in recent
      models of cortical learning and memory, and we previously demonstrated both long
      term synaptic potentiation (LTP) and long-term synaptic depression (LTD) in the
      neocortex of the unanaesthetized adult rat. Here, we have examined the effects of
      N-methyl-D-aspartate receptor (NMDAR) blockade on the induction of LTD, LTP, and
      depotentiation of field potentials evoked in sensorimotor cortex by stimulation
      of the white matter in the adult, freely moving rat. High frequency (300 Hz)
      stimulation (HFS) was used to induce LTP and prolonged, low-frequency (1 Hz)
      stimulation was used to induce either depotentiation or LTD. LTD was expressed as
      a reduction in the amplitude of the short and long-latency field potential
      components, while depotentiation was expressed as a decrease in the amplitude of
      a previously enhanced late component. Under NMDAR blockade, HFS failed to induce
      LTP and instead produced a depression effect similar to LTD. Following washout of
      the drug, HFS induced a normal LTP effect. Unlike LTP, LTD and depotentiation
      were found to be NMDAR-independent in the neocortex of the freely moving rat.

PMID- 15501587
TI  - Sequential activation of microcircuits underlying somatosensory-evoked potentials
      in rat neocortex.
AB  - Evoked cortical field potentials are widely used in neurophysiological studies
      into cortical functioning, but insight in the underlying neural mechanisms is
      severely hampered by ambiguities in the interpretation of the field potentials.
      The present study aimed at identifying the precise relationships between the
      primary evoked cortical field potential (the positive-negative [P1-N1]response)
      and the temporal and spatial sequence in which different local cortical micro
      circuits are recruited. We electrically stimulated the median nerve and recorded
      field potentials using a 12-channel depth probe in somatosensory cortex of
      ketamine anesthetized rats. Current source density analysis was used and a grand
      average was constructed based on all individual animals taking into account
      individual differences in cortical layering. Manipulation of stimulus strength,
      selective averaging of single trial responses, and double-pulse stimulation, were
      used to help disentangle overlapping dipoles and to determine the sequence of
      neuronal events. We discriminated three phases in the generation of the P1-N1
      wave. In the first phase, specific thalamic afferents depolarize both layer III
      and layer V pyramidal cells. In the second phase, superficial pyramidal cells are
      depolarized via supragranular intracortical projections. In the third phase,
      population spikes are generated in layer Vb pyramidal cells, associated with a
      distinct fast (approximately 1 ms) sink/source configuration. Axon-collaterals of
      layer Vb pyramidal cells produce an enhanced activation of the supragranular
      pyramidal cells in layer I-II, which generates N1.

PMID- 15501588
TI  - Variations of maternal care differentially influence 'fear' reactivity and
      regional patterns of cFos immunoreactivity in response to the shock-probe burying
      test.
AB  - Natural variations in maternal care in the rat influence the development of
      neuronal systems that regulate endocrine and behavioral responses to stress.
      Thus, as adults, rats that received higher levels of maternal licking/grooming
      (LG) in infancy are less 'fearful' in response to novelty, compared with adult
      offspring of Low LG mothers. The present study examined the influence of maternal
      care on behavioral and neuronal responses to a more specific, localizable form of
      threat using an electrified probe in the shock-probe burying test. Even under
      these conditions, adult offspring of High LG mothers displayed lower levels of
      fear reactivity (i.e. less shock-induced freezing and probe burying) throughout
      the test than did offspring of Low LG mothers. These differences in fearfulness
      were associated with differential patterns of cFos immunoreactivity (cFos-IR),
      120 min following test exposure. Relative to control rats exposed to a non
      electrified probe, cFos-IR was increased in the offspring of High LG mothers
      exposed to an electrified probe in the dentate gyrus, ventral subiculum, lateral
      and medial septum, nucleus accumbens and the dorsal periaqueductal gray. Shock
      exposed offspring of Low LG dams displayed a very different pattern of neuronal
      activation characterized by both increases (area CA1 of the ventral hippocampus
      and the inferior colliculus) and decreases (paraventricular nucleus of the
      hypothalamus and the ventrolateral periaqueductal gray) in cFos-IR compared with
      the no-shock controls. Together these results suggest that maternal care serves
      to 'program' neuronal circuits that modulate fear-related responding in the rat
      resulting in qualitatively different neuronal responses to stress.

PMID- 15501589
TI  - Differential upregulation of extracellular matrix molecules associated with the
      appearance of granule cell dispersion and mossy fiber sprouting during
      epileptogenesis in a murine model of temporal lobe epilepsy.
AB  - We have investigated changes in the extracellular matrix of the hippocampus
      associated with the early progression of epileptogenesis in a murine model of
      temporal lobe epilepsy using immunohistochemistry. In the first week following
      intrahippocampal injection of the glutamate agonist, domoate, there is a latent
      period at the end of which begins a sequential upregulation of extracellular
      matrix (ECM) molecules in the granule cell layer of the dentate gyrus, beginning
      with neurocan and tenascin-C. This expression precedes the characteristic
      dispersion of the granule cell layer which is evident at 14 days post-injection
      when the first recurrent seizures can be recorded. At this stage, an upregulation
      of the chondroitin sulfate proteoglycan, phosphacan, the DSD-1 chondroitin
      sulfate motif, and the HNK-1 oligosaccharide are also observed. The expression of
      these molecules is localized differentially in the epileptogenic dentate gyrus,
      especially in the sprouting molecular layer, where a strong upregulation of
      phosphacan, tenascin-C, and HNK-1 is observed but there is no expression of the
      proteoglycan, neurocan, nor of the DSD-1 chondroitin sulfate motif. Hence, it
      appears that granule cell layer dispersion is accompanied by a general increase
      in the ECM, while mossy fiber sprouting in the molecular layer is associated with
      a more restricted repertoire. In contrast to these changes, the expression of the
      ECM glycoproteins, laminin and fibronectin, both of which are frequently
      implicated in tissue remodelling events, showed no changes associated with either
      granule cell dispersion or mossy fiber sprouting, indicating that the
      epileptogenic plasticity of the hippocampus is accompanied by ECM interactions
      that are characteristic of the CNS.

PMID- 15501590
TI  - Proteomic signatures and aberrations of mouse embryonic stem cells containing a
      single human chromosome 21 in neuronal differentiation: an in vitro model of Down
      syndrome.
AB  - Neurodegeneration in fetal development of Down syndrome (DS) patients is proposed
      to result in apparent neuropathological abnormalities and to contribute to the
      phenotypic characteristics of mental retardation and premature development of
      Alzheimer disease. In order to identify the aberrant and specific genes involved
      in the early differentiation of DS neurons, we have utilized an in vitro neuronal
      differentiation system of mouse ES cells containing a single human chromosome 21
      (TT2F/hChr21) with TT2F parental ES cells as a control. The paired protein
      extracts from TT2F and TT2F/hChr21 cells at several stages of neuronal
      differentiation were subjected to two-dimensional polyacrylamide gel
      electrophoresis protein separation followed by matrix-assisted laser
      desorption/ionization-time of flight mass spectrometry to identify the proteins
      differentially expressed between TT2F and TT2F/hChr21 cells. We provide here a
      novel set of specific gene products altered in early differentiating DS neuronal
      cells, which differs from that identified in adult or fetal brain with DS. The
      aberrant protein expression in early differentiating neurons, due to the hChr21
      gene dosage effects or chromosomal imbalance, may affect neuronal outgrowth,
      proliferation and differentiation, producing developmental abnormalities in
      neural patterning, which eventually leads to formation of a suboptimal
      functioning neuronal network in DS.

PMID- 15501591
TI  - Cytokine changes in the horizontal diagonal band of Broca in the septum after
      running and stroke: a correlation to glial activation.
AB  - The relationship between running, glial cell activation and pro-inflammatory
      cytokines was studied in the context of neuroprotection against ischemic stroke
      induced by middle cerebral artery occlusion (MCAO). This was investigated in four
      groups of rats, namely, (1) nonrunner, (2) runner after 12 weeks of treadmill
      running, (3) nonrunner with MCAO and (4) runner with MCAO. The horizontal
      diagonal band of Broca (HDB) in the septum was scrutinized for qualitative cum
      quantitative changes in the microglia and astrocytes. Reverse transcription
      polymerase chain reaction and immunoblot work were carried out in the forebrain
      homogenate to determine, respectively, the gene and protein expression of several
      pro-inflammatory cytokines. Our results indicated that the runner exhibited less
      immunoreactivity and reduced numbers of glial cells within the HDB compared with
      the nonrunner. Interestingly, the mRNA and protein levels of tumor necrosis
      factor-alpha, interleukin (IL)-1beta, IL-6 and interferon-gamma, were
      significantly downregulated in the runner. Our data also suggest albeit with some
      inconsistency that the runner/MCAO rats had benefited from running. These
      observations suggest that running can result in changes to the microenvironment,
      in which the microglia and astrocytes exist in a state of quiescence concomitant
      with a reduced expression of pro-inflammatory cytokines, that may lead to
      beneficial effects seen in ischemic stroke induced by MCAO.

PMID- 15501593
TI  - Neural basis of emotional self-regulation in childhood.
AB  - Emotional self-regulation plays a pivotal role in socialization and moral
      development. This capacity critically depends on the development of the
      prefrontal cortex (PFC). The present functional magnetic resonance imaging study
      was conducted to identify the neural circuitry underlying voluntary self
      regulation of sadness in healthy girls (aged 8-10). A 2 x 2 factorial design was
      implemented with Emotion (No Sadness vs. Sadness) and Regulation (No Reappraisal
      vs. Reappraisal) as factors. In the No Reappraisal conditions, subjects were
      instructed to react normally to neutral and sad film excerpts whereas in the
      Reappraisal conditions, subjects were asked to voluntarily suppress any emotional
      reaction in response to comparable stimuli. A significant interaction of the
      Emotion and Regulation factors revealed that reappraisal of sad film excerpts was
      associated with bilateral activations of the lateral PFC (LPFC; Brodmann areas
      [BA] 9 and 10), orbitofrontal cortex (OFC; BA 11), and medial PFC (BA 9 and 10).
      Significant loci of activations were also detected in the right anterior
      cingulate cortex (BA 24/32) and right ventrolateral PFC (BA 47). In an identical
      study previously conducted by our group in adult women [Biol Psychiatry 53 (2003)
      502], reappraisal of sad film excerpts was associated with activation of the
      right OFC (BA 11) and right LPFC (BA 9). The greater number of prefrontal loci of
      activation found in children relative to adults during voluntary self-regulation
      of sadness may be related to the immaturity of the prefronto-limbic connections
      in childhood.

PMID- 15501592
TI  - Expression and immunolocalization of the multidrug resistance proteins, MRP1-MRP6
      (ABCC1-ABCC6), in human brain.
AB  - Multidrug resistance proteins (MRPs, symbol ABCC) are membrane glycoproteins that
      mediate the ATP-dependent export of organic anions, including cytotoxic and
      antiviral drugs, from cells. To identify MRP family members possibly involved in
      the intrinsic resistance of human brain to cytotoxic and antiviral drugs, we
      analyzed the expression and localization of MRP1-MRP6 in rapidly frozen
      perilesional samples of several regions of adult human brain obtained during
      neurosurgery. Quantitative polymerase chain reaction analysis showed expression
      of MRP1, MRP2, MRP3, MRP4, and MRP5 mRNA, whereas MRP6 mRNA was below
      detectability. However, immunofluorescence microscopy of cryosections from human
      brain showed no reactivity for the MRP2 or MRP3 proteins. The proteins MRP1,
      MRP4, and MRP5 were clearly localized by confocal laser scanning microscopy to
      the luminal side of brain capillary endothelial cells. The MRP4 and MRP5 proteins
      were also detected in astrocytes of the subcortical white matter. Notably, MRP5
      protein was present in pyramidal neurons. MRP proteins may, thus, contribute to
      the cellular efflux of endogenous anionic glutathione or glucuronate conjugates
      (substrates for MRP1), cyclic nucleotides (substrates for MRP4 and MRP5), or
      glutathione (co-substrate for MRP1 and MRP4); in addition, they may play an
      important role in the resistance of the brain to several cytotoxic and antiviral
      drugs.

PMID- 15501594
TI  - Postnatal expression of the plasticity-related nerve growth factor-induced gene A
      (NGFI-A) protein in the superficial layers of the rat superior colliculus:
      relation to N-methyl-D-aspartate receptor function.
AB  - Immediate early gene expression in the CNS is induced by sensory stimulation and
      seems to be involved in long-term synaptic plasticity. We have used an
      immunohistochemical method to detect the nerve growth factor-induced gene A (NGFI
      A) protein expression in the superficial layers of the rat superior colliculus
      during postnatal development. Our goal was to correlate the expression of this
      candidate plasticity protein with developmental events, especially the activity
      dependent refinement of the retinocollicular and corticocollicular pathways. We
      have also investigated the N-methyl-D-aspartate (NMDA)-receptor dependence of the
      NGFI-A expression. Animals of various postnatal ages were used. Postnatal day (P)
      12 and older animals were submitted to a protocol of dark adaptation followed by
      light stimulation. NGFI-A expression was never observed during the first 2
      postnatal weeks. The first stained cells were observed at P15, 2 days after eye
      opening (P13). The highest number of stained cells was observed at the end of the
      third postnatal week (P22). Adult-like level of expression was reached at P30,
      since at this age, the number of stained cells was comparable to that found in
      adult rats (P90). Both P22 animals submitted to an acute treatment with MK-801
      (i.p. injection) and adult animals submitted to chronic intracranial infusion of
      a MK-801 presented a clear decrease in the NGFI-A expression in response to light
      stimulation. These results suggest that the NGFI-A expression is dependent on the
      NMDA receptor activation, and the observed pattern of expression is in close
      agreement with previous descriptions of the changes in the NMDA receptor-mediated
      visual activity in the developing rat superior colliculus (SC). Our results
      suggest that the plasticity-related NGFI-A protein might play a role in the
      developmental plasticity of the superficial layers of the rat SC after eye
      opening.

PMID- 15501595
TI  - An animal model of chronic placental insufficiency: relevance to
      neurodevelopmental disorders including schizophrenia.
AB  - Evidence now suggests that compromised prenatal brain development may increase
      the risk for the manifestation of neurological disorders such as schizophrenia.
      We present a guinea-pig model which mimics a condition of human pregnancy,
      namely, chronic placental insufficiency. Previously we reported that at term
      there are changes in the brains of these offspring which are relevant to changes
      in patients with schizophrenia. The aim of this study was to examine whether
      deficits in brain structure persist to adolescence and young adulthood (8-12
      weeks) and have implications for behavioral function. Reduced uteroplacental
      blood flow was induced via unilateral ligation of the uterine artery at mid
      gestation. The brain was examined in control and prenatally compromised (PC)
      animals 8 weeks after birth using morphometric and immunohistochemical markers.
      In a separate cohort of animals, prepulse inhibition (PPI) of the acoustic
      startle response was assessed at 4, 8 and 12 weeks of age. Brain neurochemistry
      was examined by determining the concentrations of dopamine and its metabolite,
      dihydroxyphenylacetic acid (DOPAC), at 12 weeks using high performance liquid
      chromatography. In PC animals compared with controls there was a reduction in
      brain weight, persistent enlargement of the lateral ventricles, a reduction in
      the volume of the basal ganglia and septal region and no evidence of gliosis. No
      differences were observed in concentration of catecholamines in any brain region
      examined. At 12, but not 4 or 8, weeks of age, PPI was reduced in PC animals
      compared with controls. The findings of reduced brain weight, ventriculomegaly,
      reduced basal ganglia volume and absence of astrogliosis in the PC guinea-pig
      brain at adolescence parallel some of the changes observed in patients with
      schizophrenia. The impairment of PPI is comparable to sensorimotor gating
      deficits observed in patients with schizophrenia. These results indicate that
      adverse prenatal conditions lead to long-term alterations in brain structure and
      function which resemble alterations seen in patients with schizophrenia and
      therefore support the early neurodevelopmental hypothesis of schizophrenia.

PMID- 15501596
TI  - Cell death in the rat hippocampus in a model of prenatal brain injury: time
      course and expression of death-related proteins.
AB  - Survival rates have increased dramatically for very premature (gestational week
      24-28) infants. However, many of these infants grow up to have profound
      cognitive, motor and behavioral impairments due to brain damage. We have
      developed a novel model of prenatal infant gray matter injury. During the
      neonatal period, GABA is an excitatory neurotransmitter. GABA(A) receptor
      activation results in chloride efflux and membrane depolarization sufficient to
      open L-type voltage sensitive calcium channels. Our model involves excessive
      GABA(A) receptor activation in the newborn rat, with damage due to the resultant
      excessive calcium influx, not GABA(A) receptor activation itself. A common
      feature among numerous insult pathologies in the neonatal brain is an elevation
      in the intracellular levels of calcium. The goals of the present study were: 1)
      to document the time course and amount of cell death (both apoptotic and
      necrotic), and 2) to investigate the effect of GABA(A) receptor activation on the
      time course and expression of three cell death-related proteins (caspase-9, bax
      and bcl-2) in our model of prenatal brain injury. The magnitude of cell death,
      using TdT-mediated dUTP nick end labeling and Cresyl Violet to quantify the
      incidence of apoptotic and necrotic cells, was region dependent
      (CA1>CA2/3>dentate gyrus) and persisted for at least 5 days following insult.
      There was a relative increase in the amount of bax to bcl-2 protein, and
      increased protein levels of caspase-9, indicative of cell death. These findings
      are consistent with mechanisms of cell death seen in other types of early brain
      insult, and highlight a conserved cascade of events leading to cell death in the
      developing brain.

PMID- 15501597
TI  - The role of utrophin and Dp71 for assembly of different dystrophin-associated
      protein complexes (DPCs) in the choroid plexus and microvasculature of the brain.
AB  - In the brain, utrophin is present in the choroid plexus epithelium and vascular
      endothelial cells, whereas the short C-terminal isoform of dystrophin (Dp71) is
      localized in the glial end-feet surrounding blood vessels. Both proteins serve as
      anchors for the so-called dystrophin-associated protein complex (DPC), composed
      of isoforms of syntrophin, dystroglycan and dystrobrevin. Numerous transporter
      proteins and channels have a polarized distribution in vascular endothelial cells
      and in glial end-feet, suggesting an association with the DPC. We investigated
      the composition and localization of the DPC in dependence on the anchoring
      proteins in mice lacking either utrophin (utrophin0/0) or dystrophin isoforms
      (mdx3Cv). Three distinct complexes were identified: (i) associated with utrophin
      in the basolateral membrane of the choroid plexus epithelium, (ii) associated
      with utrophin in vascular endothelial cells, and (iii) associated with Dp71 in
      the glial end-feet. Upon ablation of utrophin or Dp71, the corresponding DPCs
      were disrupted and no compensation of the missing protein by its homologue was
      observed. Association of the water channel aquaporin 4 with the glial DPC
      likewise was disrupted in mdx3Cv mice. These results demonstrate the essential
      role of utrophin and Dp71 for assembly of the DPC and suggest that these proteins
      contribute to the proper functioning of the cerebrospinal fluid and blood-brain
      barriers.

PMID- 15501598
TI  - Neuroadaptive changes in the mesoaccumbens dopamine system after chronic nicotine
      self-administration: a microdialysis study.
AB  - There is little evidence to date to indicate if mesoaccumbens dopamine function
      at the neurochemical level is altered during early abstinence from chronic i.v.
      nicotine self-administration. Thus, a quantitative microdialysis (no-net-flux)
      approach was used to measure basal extracellular concentrations and extraction
      fractions of dopamine in the nucleus accumbens (ACB) of rats that self
      administered nicotine i.v. for 25 days, as well as in rats serving as yoked
      comparison groups (yoked nicotine and yoked saline). After 24-48 h of the final
      self-administration session, there was a significant reduction in basal
      extracellular dopamine levels in the ACB of the self-administration group
      compared with the yoked saline group (1.35+/-0.15 nM versus 3.70+/-0.28 nM). The
      basal extracellular dopamine levels in the yoked nicotine group (1.46+/-0.20 nM)
      were not significantly different compared with the nicotine self-administration
      group. The in vivo extraction fraction of dopamine, an indirect measure of
      dopamine uptake, was significantly increased in the nicotine self-administration
      (86%) and yoked nicotine (91%) groups compared with the yoked saline group (77%).
      In addition, a marked reduction in the elevation of extracellular dopamine levels
      in the ACB occurred after a nicotine challenge as measured by conventional
      microdialysis in the self-administration (112% of basal) and yoked nicotine (121%
      of basal) groups as compared with a yoked saline (154% of basal) group. The
      reduced basal ACB dopamine levels in the nicotine groups during early abstinence
      appears to be due to increased clearance, suggesting increased dopamine uptake is
      occurring as a result of the chronic nicotine treatment. The reduced elevation of
      extracellular dopamine levels in the ACB upon nicotine challenge suggests a
      functional desensitization or downregulation phenomenon involving acetylcholine
      receptors (nicotinic nAChRs). Overall, these results provide clear evidence for a
      neuroadaptive change that alters dopamine transmission in the ACB during
      abstinence from chronic i.v. nicotine exposure.

PMID- 15501599
TI  - Bilateral microinjections of vigabatrin in the central piriform cortex retard
      amygdala kindling in rats.
AB  - The piriform cortex (PC) is the largest region of the mammalian olfactory cortex
      with strong connections to limbic structures, including the amygdala,
      hippocampus, and entorhinal cortex. Various previous studies in rodents suggest
      that the PC might be very important in the development and maintenance of limbic
      kindling, i.e. a widely used model of temporal lobe epilepsy. GABAergic
      inhibition in the transition zone between the anterior and posterior PC, termed
      here central PC, seems to be particularly involved in the processes leading to
      progression of kindled seizures. This prompted us to study whether elevation of
      GABA levels in this subregion of the PC by bilateral microinjection of vigabatrin
      is capable of suppressing amygdala kindling. Rats were stimulated once daily
      until fully kindled (stage 5) seizures had developed. Vigabatrin (10 microg) was
      injected 24 h before the first stimulation as well as 6 h before the 5th and 10th
      stimulation, which approximately doubled the number of stimulations required for
      kindling development compared with controls. This marked retardation of kindling
      acquisition was predominantly due to a significant inhibition of the progression
      from stage 1 to stage 2 and stage 3 to stage 4 seizures, demonstrating that
      microinjection of vigabatrin into the central PC markedly inhibits the
      progression and secondary generalization of focal seizures emanating from the
      amygdala.

PMID- 15501600
TI  - Central projections of sensory innervation of the rat superior sagittal sinus.
AB  - The central projections of the rat superior sagittal sinus (SSS) sensory
      innervation were studied by transganglionic tract tracing techniques. Cholera
      toxin subunit b (CTb) or wheat germ agglutinin-horseradish peroxidase conjugate
      (WGA-HRP) was applied on the overlying dura of the SSS and labeled terminations
      in the brainstem and cervical spinal cord were examined under the light
      microscope. Labeled cell bodies were seen bilaterally in the trigeminal ganglia
      and in the C2 dorsal root ganglia following both CTb and WGA-HRP applications. In
      the brainstem, labeled terminations were mainly found in the caudal and
      interpolar parts of the spinal trigeminal nucleus. In the CTb cases, terminations
      were also found in the dorsolateral part of the cuneate nucleus. In the spinal
      cord, labeled terminations were primarily located in the most ventrolateral part
      of the C1-C3 spinal dorsal horns on both sides. WGA-HRP labeled terminations were
      mainly located in laminae I and II, whereas CTb-labeled terminations located in
      laminae III and IV. These results indicate that the sensory information from the
      SSS is transmitted through both trigeminal and cervical spinal nerve branches to
      a primary sensory nervous center that extends from the C3 dorsal horn until to
      the interpolar part of the spinal trigeminal nucleus.

PMID- 15501601
TI  - Vagal afferent input from the acid-challenged rat stomach to the brainstem:
      enhancement by interleukin-1beta.
AB  - Exposure of the gastric mucosa to back-diffusing concentrations of HCl (0.25 M,
      pH 0.51) stimulates vagal afferent input to the brainstem. Here we have examined
      whether pretreatment of rats with the proinflammatory cytokines interleukin-1beta
      and tumor necrosis factor-alpha causes sensitization of vagal afferent pathways
      to HCl. Rats were pretreated i.p. with interleukin-1beta, tumor necrosis factor
      alpha (10 microg/kg) or their vehicle (sterile saline) 24, 48 and 96 h before
      intragastric administration of HCl (0.25 M, 1 ml/100 g). Activation of neurons in
      the nucleus tractus solitarii was visualized by c-Fos immunohistochemistry 2 h
      after the HCl challenge. I.p. administration of interleukin-1beta and tumor
      necrosis factor-alpha alone induced c-Fos in the brainstem, an effect that was
      gone after 24 h. At this time, however, the effect of HCl to cause expression of
      c-Fos in the nucleus tractus solitarii was significantly enhanced by pretreatment
      with interleukin-1beta and tumor necrosis factor-alpha. The sensitizing effect of
      i.p.-administered interleukin-1beta was sustained for more than 48 h and
      prevented by the interleukin-1 receptor antagonist anakinra. Intracisternal
      administration of interleukin-1beta and tumor necrosis factor-alpha (100 ng)
      failed to amplify the HCl-evoked expression of c-Fos in the brainstem. These
      results show that peripheral administration of the proinflammatory cytokines
      interleukin-1beta and tumor necrosis factor-alpha induces prolonged sensitization
      of vagal afferent pathways to gastric HCl challenge. This effect seems to arise
      from a peripheral action on vagal afferents and may be of relevance to gastric
      chemonociception.

PMID- 15501602
TI  - Integrin alpha2beta1 affects mechano-transduction in slowly and rapidly adapting
      cutaneous mechanoreceptors in rat hairy skin.
AB  - The role of a transmembrane protein, integrin alpha2beta1, to modulate the neural
      responses of cutaneous mechanoreceptors to mechanical indentation was examined
      using an isolated skin-nerve preparation in a rat model. Skin and its intact
      innervation were harvested from the medial thigh of the hindlimb and placed in a
      dish containing synthetic interstitial fluid. Using a standard teased nerve
      preparation, the neural responses of single slowly or rapidly adapting
      mechanoreceptors (SA or RA, respectively) were identified and the afferents
      categorized according to standard protocols (i.e. response to constant stimuli).
      The most sensitive spot of a mechanoreceptor's receptive field was identified and
      then stimulated using controlled compressive stress (constant or dynamic loads
      between threshold and saturation load for SAs and RAs, respectively). Loads were
      applied before, during, and after passive diffusion into the skin of a function
      blocking anti-integrin alpha2 monoclonal antibody (FBmAb) or one of two types of
      control antibodies (immunoglobulin G or a FBmAb conjugated with a secondary
      antibody). The sensitivities of both SA and RA mechanoreceptors were profoundly
      reduced in the presence of the FBmAb, while not changing the waveforms of their
      action potentials or their adaptation properties. Both control antibodies had no
      significant effect on mechanoreceptors' sensitivities. Following removal of the
      FBmAb, the effects in some neurons were partially reversible. Taken together, the
      data from this study support the hypothesis that integrin alpha2beta1 plays a
      significant role in modulating mechanoreceptive response to compressive
      indentation.

PMID- 15501603
TI  - Evidence for macular gravity receptor modulation of hypothalamic, limbic and
      autonomic nuclei.
AB  - Mice lacking normal vestibular gravity reception show altered homeostatic,
      circadian and autonomic responses to hypergravity (+G) exposure. Using c-Fos as a
      marker of neuronal activation, the current study identifies CNS nuclei that may
      be critical for initiating and integrating such responses to changes in
      vestibular signaling. This experiment utilized the mutant C57BL/6JEi-het mouse
      (het), which lacks macular otoconia and thus gravity receptor function. Following
      2 h of 2G (2x Earth's gravity) exposure (via centrifugation) the neuronal
      responses of the het mice were compared with wildtype mice similarly exposed to
      2G, as well as het and wildtype 1G controls. Wildtype mice exposed to 2G
      demonstrated robust c-Fos expression in multiple autonomic, hypothalamic and
      limbic nuclei, including: the lateral septum, bed nucleus of the stria
      terminalis, amygdala, paraventricular hypothalamus, dorsomedial hypothalamus,
      arcuate, suprachiasmatic hypothalamus, intergeniculate leaflet, dorsal raphe,
      parabrachial and locus coeruleus. The het mice exposed to 2G demonstrated little
      to null c-Fos expression in these nuclei with a few exceptions and, in general, a
      similar pattern of c-Fos to 1G controls. Data from this study further support the
      existence of a complex and extensive influence of the neurovestibular system on
      homeostatic, circadian and possibly autonomic regulatory systems.

PMID- 15501604
TI  - Rapid upregulation of mu opioid receptor mRNA in dorsal root ganglia in response
      to peripheral inflammation depends on neuronal conduction.
AB  - S.c. painful inflammation leads to an increase in axonal transport of opioid
      receptors from dorsal root ganglia (DRG) toward the periphery, thus causing a
      higher receptor density and enhanced opioid analgesia at the injured site. To
      examine whether this increase is related to transcription, the mRNA of Delta-
      (DOR) and mu-opioid receptor (MOR) in lumbar DRG was quantified by real time
      Light Cycler polymerase chain reaction (LC-PCR), and correlated to ligand binding
      in DRG and sciatic nerve. In normal DRG, DOR mRNA was seven times less abundantly
      expressed than MOR mRNA. After induction of unilateral paw inflammation, mRNA
      content for DOR remained unchanged, but a bi-phasic upregulation for MOR mRNA
      with an early peak at 1-2 h and a late increase at 96 h was found in ipsilateral
      DRG. As no changes were observed in DRG of the non-inflamed side, this effect was
      apparently not systemically mediated. A significant increase in binding of the
      MOR ligand DAMGO was detected after 24 h in DRG, and after early and late
      ligation in the sciatic nerve, indicating an enhanced axonal transport of MOR in
      response to inflammation. The early increase in MOR mRNA could be completely
      prevented by local anesthetic blockade of neuronal conduction in sciatic nerve.
      These data suggest that mRNA of the two opioid receptors DOR and MOR is
      differentially regulated in DRG during peripheral painful inflammation. The
      apparently increased axonal transport of MOR in response to this inflammation is
      preceded by upregulated mRNA-transcription, which is dependent on neuronal
      electrical activity.

PMID- 15501605
TI  - Pallidal control of substantia nigra dopaminergic neuron firing pattern and its
      relation to extracellular neostriatal dopamine levels.
AB  - The firing patterns of dopaminergic neurons in vivo are strongly modulated by
      afferent input. The principal GABAergic inputs to the dopaminergic neurons of the
      substantia nigra originate from neurons of the neostriatum, globus pallidus and
      substantia nigra pars reticulata. It has previously been shown that the firing
      pattern of nigral dopaminergic neurons can be manipulated by pharmacologically
      induced excitation or inhibition of the globus pallidus with relatively little
      effect on firing rate. We used this technique to explore the relation between the
      firing pattern of dopaminergic neurons and extracellular dopamine levels in the
      neostriatum in vivo. Specifically, we tested whether an increase in burst firing
      in dopaminergic neurons produced by increased pallidal activity led to increased
      extracellular dopamine levels in the neostriatum. Single unit extracellular
      recording combined with simultaneous microdialysis was used to measure the firing
      rates and patterns of dopaminergic neurons and extracellular striatal dopamine
      levels, respectively, during bicuculline-induced excitation of the globus
      pallidus. Pallidal excitation resulted in a marked increase in burst firing in
      dopaminergic neurons along with only a slight increase in firing rate, but
      produced a significant elevation (approximately 45%) in neostriatal dopamine
      levels. These data suggest that afferent-induced burst firing in dopaminergic
      neurons leads to an increase in extracellular dopamine levels in the neostriatum
      when compared with less bursty patterns with similar overall firing rates.

PMID- 15501606
TI  - Scaling of prediction error does not confirm chaotic dynamics underlying
      irregular firing using interspike intervals from midbrain dopamine neurons.
AB  - Dopamine neurons in the substantia nigra pars compacta often fire in an
      irregular, single spike mode in vivo, and a similar firing pattern can be
      observed in vitro when small conductance calcium-activated potassium channel
      blockers are applied to the bath. It is not clear whether the irregular firing is
      due to stochastic processes or nonlinear deterministic processes. A previous
      study [Neuroscience 104 (2001) 829] used nonlinear forecasting methods applied to
      a continuous function derived from the interspike interval (ISI) data from
      irregularly firing dopamine neurons to show that the predictability scaled
      exponentially with forecast horizon and was consistent with nonlinear
      deterministic chaos. However, we show here that the observed exponential scaling
      is also consistent with a stochastic process, because it did not differ
      significantly from that of shuffled surrogate data. On the other hand, nonlinear
      forecasting directly from the ISI data using the package TISEAN provided some
      evidence for nonlinear deterministic structure in four of five records obtained
      in vitro and in two of nine records obtained in vivo. Although we cannot rule out
      a role for nonlinear chaotic dynamics in structuring the firing pattern, we
      suggest an alternate hypothesis that includes a mechanism by which the firing
      pattern can become more variable in the presence of a constant level of
      background noise.

PMID- 15501607
TI  - Resetting of 'synaptic tags' is time- and activity-dependent in rat hippocampal
      CA1 in vitro.
AB  - We have recently proposed that the maintenance of hippocampal long-term
      potentiation (LTP) and depression depends on at least two required processes:
      induction of LTP must set (1) process-specific 'synaptic tags' which capture (2)
      process-unspecific plasticity-related proteins (PRPs), synthesized via a
      heterosynaptic interaction [Neurobiol Learn Mem 82 (2004) 12]. The 'tag' as well
      as the PRPs are characterized by a relatively short half-life of several minutes
      up to a few hours before they degrade most likely by processes such as
      dephosphorylation. The question now arose whether the 'tags' can also be reset in
      an activity-dependent manner, thus preventing the processing of PRPs with the
      result of transient short-lasting plasticity. Here we have investigated this
      topic during early-LTP and found that low-frequency stimulation shortly after
      early-LTP-induction (5 min) resets the 'tag' or the 'tag complex' of
      macromolecules preventing any lasting forms of LTP and thus, preventing the
      formation of a memory trace.

PMID- 15501608
TI  - S-Adenosylmethionine (SAMe) attenuates acetaminophen hepatotoxicity in C57BL/6
      mice.
AB  - Hepatic toxicity is associated with excessive dosages of the over the counter
      analgesic, acetaminophen (APAP). The aim of this study was to explore protection
      by the nutritional agent S-adenosylmethionine (SAMe) on APAP hepatotoxicity. Male
      C57BL/6 mice were injected intraperitoneal (i.p.) with 500 mg/kg (15 ml/kg) APAP
      or water vehicle (VEH). SAMe was injected i.p. at a dose of either 1000 mg/kg (5
      ml/kg) just prior or 500 mg/kg SAMe 15 min prior to administration of VEH or
      APAP. Comparison of groups showed that SAMe reduced APAP toxicity. Plasma alanine
      aminotransferase (ALT) levels were increased 2 and 4 h after APAP administration
      when compared to vehicle (VEH) controls. Liver weight was increased relative to
      the VEH group within 4 h after APAP treatment. Histological examination by light
      microscopy confirmed small changes in morphology within 2 h after APAP injection
      and marked centrilobular necrosis within 4 h in the APAP group. In contrast, when
      APAP was administered to SAMe pretreated mice, ALT and liver weights were
      comparable to the VEH and SAMe groups. Histological examination also showed that
      SAMe produced a marked protection in APAP mediated centrilobular necrosis at 4 h
      after APAP injection. APAP administration depressed hepatic glutathione levels
      when monitored at 2 and 4 h. Lipid peroxidation was induced above VEH values 2
      and 4 h after APAP injection. Consistent with the SAMe protection of APAP hepatic
      toxicity, the expected depletion of hepatic glutathione (GSH) levels by APAP was
      prevented by SAMe pretreatment. SAMe pretreatment also prevented the induction of
      lipid peroxidation at 2 and 4 h post-APAP administration. In conclusion, SAMe
      provides protection from APAP hepatic toxicity at 2 and 4 h post-APAP injection.
      SAMe pretreatment prevented APAP associated depletion in hepatic glutathione and
      induction of lipid peroxidation as part of its mechanism of protection.

PMID- 15501609
TI  - Neutrophil-mediated formation of carcinogenic N-nitroso compounds in an in vitro
      model for intestinal inflammation.
AB  - In order to study neutrophil-mediated formation of carcinogenic N-nitroso
      compounds as a mechanism of inflammation-related colon carcinogenesis, we
      designed an in vitro model for intestinal inflammation, consisting of a
      coincubation system with human colon cells (Caco-2 cells) and activated human
      neutrophils (PMN), as important immunoreactive cells. We investigated whether
      nitrosamines and nitrosamides could be formed upon addition of dimethylamine,
      morpholine and methylurea to the coincubations as nitrosatable precursors, which
      are known to produce carcinogenic N-nitroso compounds. Incubations of pure nitric
      oxide with dimethylamine and morpholine showed that NO-mediated formation of
      nitrosodimethylamine and nitrosomorpholine is possible under the incubation
      conditions. During the coincubations of activated PMN and Caco-2 cells, 0.34 nmol
      nitrite/10(6) PMN was produced. Dose-dependent formation of NMOR was observed in
      this PMN/Caco-2 system; addition of 5mM morpholine resulted in a significantly
      increased NMOR formation of 4.2 nM. However, no detectable NDMA and
      methylnitrosourea were formed in this coincubation system. These results suggest
      that activated human neutrophils are able to synthesize carcinogenic N
      nitrosamines, e.g. NMOR, which implies a risk of colon carcinogenesis during
      chronic inflammation. However, the observed relatively low level of nitrosation
      suggests that also other risk factors are contributing to the association between
      chronic inflammation and colon cancer risk.

PMID- 15501610
TI  - Mercury concentrations in brain and kidney following ethylmercury, methylmercury
      and Thimerosal administration to neonatal mice.
AB  - The distribution of mercury to the brain following an injection of methylmercury
      (MeHg) or ethylmercury (EtHg) was examined in immature mice. Postnatal day (PND)
      16 CD1 mice received MeHg chloride either by IM injection or by gavage. At 24 h
      and 7 days post-injection, total mercury concentrations were determined in blood,
      kidney, brain, and muscle by cold vapor atomic fluorescence spectrometry. At 24
      h, an IM injection of MeHg chloride (17.4 microg) produced total mercury
      concentrations in the blood (6.2 +/- 0.9 microg/g), brain (5.6 +/- 1.3 microg;
      0.6% delivered dose), and kidney (25.2 +/- 5.6 microg; 1.1%), approximately 30%
      of that obtained from oral administration (blood: 17.9 +/- 1.0 microg; brain:
      16.1 +/- 1.2 microg, 1.5%; kidney: 64.9 +/- 6.3 microg, 2.7%). For comparison,
      PND 16 mice received an IM injection of concentrated dosing suspensions (2 microl
      dosing vol.) for EtHg chloride (6 microg) or Thimerosal (15.4 microg). For EtHg,
      approximately 0.39 +/- 0.06% of the injected mercury was detected in the brain
      and 3.5 +/- 0.6% in the kidney at 24 h. Thimerosal IM injection resulted in 0.22
      +/- 0.04% in the brain, and 1.7 +/- 0.3% in the kidney. By 7 days, mercury levels
      decreased in the blood but were unchanged in the brain. An acute IM injection to
      adult mice of each suspension at a 10-fold higher dose resulted an average 0.1%
      mercury in the brain, and higher levels in the blood, kidney, and muscle as
      compared to the young. In immature mice, MeHg delivered via oral route of
      administration resulted in significantly greater tissue levels as compared to
      levels from IM injection. Comparisons of tissue distribution following IM
      administration suggest that an oral route of administration for mercury is not
      comparable to an IM delivery and that MeHg does not appear to be a good model for
      EtHg-containing compounds.

PMID- 15501611
TI  - Cadmium at a non-toxic dose alters gene expression in mouse testes.
AB  - The testes are important targets of cadmium (Cd)-induced toxicity and
      carcinogenicity in rodents. Exposure to Cd at environmentally relevant low levels
      is a significant human health concern, but the effects of Cd on the rodent testes
      at doses that do not cause overt lesions are poorly defined. We used cDNA
      microarray and quantitative real-time RT-PCR assays to determine gene expression
      profiles in the testes of CD-1 mice 12-72 h after a single s.c. injection of 5
      micromol/kg CdCl2. This dose of Cd did not produce overt histopathological
      changes, but clearly altered the expression of some genes that are likely to be
      important in toxicity responses. The most significant changes in gene expression
      occurred 24 h after treatment, corresponding to when the highest level of Cd was
      detected in the testes. Increased expression of the C-myc and Egr1 genes strongly
      suggests acute stress responses. Repressed expression of cell cycle-regulated
      cyclin B1 and CDC2 proteins indicates a potential for causing G2/M arrest and
      disturbance of meiosis. Decreased expression of pro-apoptotic genes, particularly
      Casp3, and DNA repair genes possibly contributes to Cd-induced carcinogenesis.
      These results indicate that changes in gene expression occur well before overt
      effects of Cd-induced testicular toxicity and carcinogenicity are apparent.

PMID- 15501612
TI  - Estimation of interindividual variation in oxidative metabolism of
      dichloromethane in human volunteers.
AB  - A modified version of the original physiologically based pharmacokinetic (PBPK)
      model by Andersen et al. (1987) has been developed and used in conjunction with
      previously published human kinetic data for dichloromethane (DCM) metabolism and
      to assess interindividual variability in the rate of oxidative metabolism. Time
      course data for 13 volunteers (10 males, 3 females) exposed to one or more
      concentrations of DCM (50 ppm, 100 ppm, 150 ppm, or 200 ppm) for 7.5h were used
      to optimize the maximal rate of hepatic metabolism (V(maxC)) through the
      cytochrome P450 pathway for each individual. DCM breath and blood concentrations
      were used, along with carboxyhemoglobin concentrations in blood and carbon
      monoxide (CO) concentrations in exhaled breath, to estimate the model parameters.
      Significant improvements in model fit were achieved when extrahepatic oxidative
      metabolism of DCM was added to the model structure. The 13 individual V(maxC)
      values ranged from 7.1 to 23.6 mg/h/kg0.7 and appeared to be bimodally
      distributed. The distribution was not sex related and may be related to
      differential CYP2E1 induction. A comparison of the observed variation in V(maxC)
      values to other estimates of variability in the rate of oxidative metabolism and
      human CYP2E1 activity suggest a relatively narrow range in human hepatic activity
      toward DCM.

PMID- 15501613
TI  - Toxicity studies on western juniper oil (Juniperus occidentalis) and Port-Orford
      cedar oil (Chamaecyparis lawsoniana) extracts utilizing local lymph node and
      acute dermal irritation assays.
AB  - The essential oil extracts of western juniper oil (Juniperus occidentalis) and
      Port-Orford-cedar oil (Chamaecyparis lawsoniana) were evaluated for possible
      dermal toxic effects on mice and rabbits. Mice were tested for their response to
      both extracts utilizing a local lymph node assay. Western juniper oil extract at
      0.5% and 5% concentrations did not show a stimulation index (SI) greater than
      normal (3.0); however, a 50% concentration did show a positive response at 3.3.
      Port-Orford-cedar oil extract did not show a positive response at concentrations
      of 0.5%, 5% or 50%. An acute dermal irritation study using rabbits had a primary
      irritation index (PII) of 3.3 with 100% Port-Orford-cedar oil extract. This was
      reduced to a PII of 0.625 when diluted 1:1 with olive oil. Undiluted western
      juniper oil extract had a PII score of 2.7. While a 5.0% solution had a PII score
      of 0.3, a 0.5% solution of western juniper oil was a non-irritant. It would
      appear that animals bedded on wood shavings have contact with essential oils at
      concentrations far less than the 2% maximum by weight obtained by steam
      distillation extraction. These concentrations did not elicit a hypersensitivity
      response.

PMID- 15501614
TI  - Altered apoptotic response in MCF 10A cells treated with the equine estrogen
      metabolite, 4-hydroxyequilenin.
AB  - Excessive exposure to synthetic and endogenous estrogens has been associated with
      the development of cancer in several tissues including the breast. 4
      Hydroxyequilenin (4-OHEN), a major catechol metabolite of equine estrogens
      present in Premarin, an estrogen replacement formulation, has been shown to
      induce apoptosis and DNA damage in human breast cancer cells. It also has the
      potential to be a tumor initiator or promoter and complete carcinogen. To further
      understand the effects and mechanisms of equine catechol estrogen metabolite 4
      OHEN action in vitro, human non-tumorigenic mammary epithelial MCF 10A cell line
      was used to study the toxic effects of 4-OHEN. In this study, we observed that 4
      OHEN caused dose-dependent increases in apoptosis and DNA damage as measured by
      the DAPI nuclear screening assay and the Comet assay, respectively.
      Interestingly, cells treated with 100 nM 4-OHEN biweekly for 4 weeks became
      resistant to cisplatin-induced apoptosis. The resistance to apoptosis of the 100
      nM 4-OHEN-treated cells was through multiple regulatory mechanisms. Compared to
      the DMSO-treated cells, the 100 nM 4-OHEN-treated cells had higher GSH levels and
      total SOD activity, and a stronger GSH response after cisplatin treatment.
      Expression levels of several genes involved in cell growth, DNA repair, and
      apoptosis were either up- or down-regulated. These data indicate that long-term
      low-level equine estrogen metabolite exposure could induce DNA damage and
      initiate cells to become resistant to apoptosis.

PMID- 15501615
TI  - Identification of 1-ethoxyethyl radicals in the reaction of ferrous ions with
      serums from rats exposed to diethyl ether.
AB  - Using alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (4-POBN) as a spin trap
      reagent, an electron paramagnetic resonance (EPR) spectrum was observed for the
      complete reaction mixture of ferrous ions with serums from rats exposed to
      diethyl ether. The EPR spectrum was not observed for the complete reaction
      mixture without the serums (or ferrous ions) or with a serum from a rat not
      exposed to diethyl ether. In order to identify the 4-POBN radical adducts, HPLC
      EPR and HPLC-EPR-MS analyses were employed. The HPLC-EPR analysis of the complete
      reaction mixture showed a prominent peak with a retention time of 25.2 min. The
      HPLC-EPR-MS analysis of the peak gave ions at m/z 181 and m/z 268. The ions m/z
      268 correspond to the protonated molecular ions of 4-POBN/1-ethoxyethyl radical
      adducts, (M + H)+. The fragment ions at m/z 181 correspond to the loss of
      [(CH3)3C(O)N] from the protonated molecular ions. The HPLC-EPR analysis of the
      Fenton reaction mixture with diethyl ether gave a peak with the same retention
      time as the one in the reaction of the rat serums with ferrous ions. Thus, the
      radicals detected in the reaction mixture of ferrous ions with the serums from
      rats exposed to diethyl ether are identified as 1-ethoxyethyl radicals.

PMID- 15501619
TI  - Diabetes is a vascular disease: the role of endothelial dysfunction in
      pathophysiology of cardiovascular disease in diabetes.
AB  - Diabetes is a vascular disease. Endothelial dysfunction is the initial process in
      vascular manifestations of diabetes mellitus (DM). There are multiple pathways
      involved in the pathophysiologic process related to endothelial dysfunction in
      DM. Most of these abnormalities occur secondary to insulin resistance. In this
      article the role of insulin, glucose,dyslipidemia, oxidative stress and various
      cellular mechanisms related to endothelial dys-function in diabetes are discussed
      in detail.

PMID- 15501618
TI  - Obesity, metabolic syndrome, and type 2 diabetes: emerging epidemics and their
      cardiovascular implications.
AB  - As we enter the twenty-first century, the burden of chronic diseases, such as
      obesity, type 2 diabetes, and CVDs, is expected to increase dramatically. These
      diseases are a consequence of several factors that include an aging
      population,changes in demographic composition, and an excess of contemporary
      lifestyle. The prevention and control of overweight, obesity, metabolic syndrome,
      and diabetes pose special challenges for clinical and public heath practice as
      well as for basic, clinical, and population science research.

PMID- 15501620
TI  - Platelet function, coagulopathy, and impaired fibrinolysis in diabetes.
AB  - Diabetes and the metabolic syndrome, including insulin resistance, that underlies
      it are hyper-coagulable states. Increased platelet reactivity,augmented activity
      of the coagulation system,and impaired fibrinolysis are characteristic and
      understood to a remarkable extent. In aggregate,these derangements contribute to
      accelerated atherosclerosis, premature coronary artery dis-ease, and a profound
      toll from both.

PMID- 15501621
TI  - Coronary atherosclerosis in diabetic subjects: clinical significance, anatomic
      characteristics, and identification with in vivo imaging.
AB  - Diabetes mellitus is an endocrine disorder that promotes the development and
      progression of atherosclerotic coronary disease. As a consequence, cardiovascular
      disease is the most important cause of morbidity and mortality in diabetics.
      Early identification and treatment of asymptomatic stages provides the
      opportunity to prevent cardiovascular end organ complications. Modem clinical
      imaging modalities allow the assessment of early atherosclerotic changes in
      coronary arteries; however, prospective evidence that atherosclerosis imaging
      impacts on clinical outcome is not yet available and future studies are
      necessary.

PMID- 15501622
TI  - Diabetes in the elderly and in women: cardiovascular risks.
AB  - The prevalence of diabetes in the United States is on the rise because of
      changing characteristics of our population. Ours is an aging population; women
      who are older than 75 years constitute the fastest growing segment of our
      population. Our population is increasingly more overweight and sedentary and the
      numbers of minority persons who have a higher prevalence of obesity and diabetes
      are on the rise. Currently, at least 17 million persons have known diabetes;
      another 4 million have the disease but have not been diagnosed. There also is a
      much larger population-perhaps up to 60 million per-sons-who has the metabolic
      syndrome. Up to 60% of persons who have essential hypertension have impaired
      insulin resistance and other characteristics of this syndrome. This article
      focuses on the metabolic syndrome and diabetes in women and the elderly.

PMID- 15501623
TI  - Diabetes mellitus and heart failure: basic mechanisms, clinical features, and
      therapeutic considerations.
AB  - Diabetic cardiomyopathy encompasses the spectrum from subclinical disease to the
      full-blown syndrome of congestive heart failure. The prevalence of type 2
      diabetes mellitus is increasing at an alarming rate in the western world. and
      with it, the frequency of diabetes-related heart failure. There is at least early
      suggestion that target-driven, long-term, intensified intervention that is aimed
      at multiple risk factors in patients who have type 2 diabetes and
      microalbuminuria may reduce the risk of macrovascular (cardiovascular) and micro
      vascular complications by approximately 50%. Thus, it is imperative that
      patients, particularly those who are at risk for the cardiovascular dysmetabolic
      syndrome, be screened aggressively for the presence of glucose intolerance and
      diabetes. When detected, all metabolic and cardio-vascular parameters should be
      evaluated and treated aggressively to reach currently recommended clinical
      targets. Such action will result in great benefit for patients by reducing
      morbidity and mortality and improving quality of life and will reduce the
      financial burden that is associated with this epidemic disease.

PMID- 15501624
TI  - Role of exercise training on cardiovascular disease in persons who have type 2
      diabetes and hypertension.
AB  - Exercise training is an essential component in the medical management of patients
      who have type 2 diabetes and hypertension. Regular exercise improves the
      cardiovascular health of individuals who have these conditions through multiple
      mechanisms (Fig. 1). These mechanisms include improvements in endothelial
      vasodilator function,left ventricular diastolic function, arterial
      stiffness.systematic inflammation, and reducing left ventricular mass. Exercise
      training also reduces total and abdominal fat, which mediate improvements in
      insulin sensitivity and blood pressure, and possibly, endothelial function.
      Persons who are in a prediabetic stage or those who have the metabolic syndrome
      may be able to prevent or delay the progression to overt diabetes by adopting a
      healthier lifestyle, of which increasing habitual levels of physical activity isa
      vital component. Most persons who have diabetes and hypertension or are at risk
      for these conditions should be able to initiate an exercise program safely after
      appropriate medical screen-ing and the establishment of an individualized
      exercise prescription. Despite the increasing amount of evidence that shows the
      benefits of exercise training, this modality of prevention and treatment
      continues to be underused. Although patients' lack of knowledge of the benefits
      of exercise or lack of motivation contributes to this underuse, a lack of clear
      and specific guidelines from health care professionals also is an important
      factor. Clinicians need to educate patients about the benefits of exercise for
      managing their type 2 diabetes and assist in formulating specific advice for
      increasing physical activity. Specific instructions should be given to patients,
      rather than general advice, such as "you should exercise more often." Many
      cardiac re-habilitation and clinical exercise programs can accommodate patients
      who have type 2 diabetes and hypertension. Such programs can establish
      individualized exercise prescriptions and provide an environment that is
      conducive for "lifestyle change" that underlies long-term compliance to exercise
      and risk factor modification.

PMID- 15501625
TI  - [Pollution level during inhalation sedation with a 50%N2O/50%O2 premix:
      comparison of two administration devices].
AB  - OBJECTIVES: Prefixed equimolar nitrous oxide and oxygen mixture (Kalinox)
      indications have risen within hospital services both as sedative and analgesic
      procedures. This study aimed to evaluate the levels of pollution associated with
      the use of two different systems of administration. STUDY DESIGN: An experimental
      trial was undertaken in a dental service for anxious patients or those with
      behavioral problems requiring nitrous oxide/ oxygen sedation for treatment.
      PATIENTS AND METHODS: Sedation was provided using either a continuous flow system
      or an on-demand system of administration of Kalinox over two consecutive periods,
      corresponding to 23 days of administration and 26 days without administration.
      The gas was administered for 122 patients in 149 procedures. The occupational
      exposure to nitrous oxide was measured continuously for the two evaluation
      periods using infrared spectrometry. The Time Weighted Average exposure (TWA)
      over eight hours was calculated for each system for each day with at least one
      sedation session. RESULTS: The mean TWA calculated for the two evolution periods
      was significantly lower with the on-demand system than where compared the
      continuous flow system (respectively 15.3 +/-23.1 and 32.3 +/-25.1 ppm; p <
      0.05). CONCLUSION: The occupational exposure to nitrous oxide generated by the
      administration of the 50% N2O/ 50%O2 premix during dental care remained within
      accepted levels in relation to national recommendations for the exposed
      personnel.

PMID- 15501626
TI  - [Continuous infusion of remifentanil and target-controlled infusion of propofol
      for coronary surgery in elderly patients: comparison with continuous infusion of
      remifentanil and propofol].
AB  - OBJECTIVES: Comparison of the length of mechanical ventilation and postoperative
      complications after coronary surgery in elderly patients anaesthetised with
      propofol associated with either alfentanil or remifentanil. STUDY DESIGN:
      Retrospective study with an historic control group. PATIENTS: Three hundred
      thirty-eight consecutive patients (75-year-old or more) undergoing isolated
      coronary surgery. One hundred and fifty seven patients operated between January
      1998 and June 2000 received alfentanil (1 microg/kg/minute) with a manually
      control infusion of propofol, 181 operated between July 2000 and 2002,
      remifentanil 0.25 microg/kg/minute with target controlled infusion of propofol
      (target blood concentration: 1.5 to 2 microg/ml). METHODS: The two groups were
      compared for preoperative and surgical data. The length of mechanical
      ventilation, stay in ICU and the main postoperative complications were compared
      between the two groups. RESULTS: Length of mechanical ventilation was
      significantly reduced in the remifentanil group (6 +/- 9 h vs. 13 +/- 63 h ; p
      <0.0001), 70% of the patients were extubated before the 6th postoperative hours
      against 53% in the alfentanil group (p =0.0023). This was not associated with a
      reduction of stay in ICU or postoperative complications. During surgery, an
      increased used of vasopressor was observed in the remifentanil group (40.2% vs
      2.4% ; p <0.0001) with a postoperative elevation of blood concentration of CKMb
      (35.7 +/- 38.2 microg/l, vs. 27.7 +/- 31.9 microg/l, p =0.02). CONCLUSION:
      Elderly patients undergoing coronary surgery were extubated earlier with
      remifentanil. However, this had no effect on duration of ICU stay but was
      associated with an increased used of vasopressor.

PMID- 15501627
TI  - [Intravenous morphine titration].
AB  - OBJECTIVES: To describe principles of intravenous (i.v.) morphine titration. To
      analyse current knowledge based on the experimental and clinical studies. To
      describe clinical implications in the operating room, postanaesthesia care unit
      (PACU), prehospital care, emergency and intensive care units (ICU), and
      cancerology. To provide recommendations for clinical practice. DATA SOURCES:
      Search in the Medline database without limitation, using the following keywords:
      morphine titration. STUDY SELECTION: All types of articles were selected
      including prospective randomised (or not randomised) studies in adults and
      children, practice guidelines, reviews, editorials and case reports. DATA
      SYNTHESIS: Intravenous (i.v.) morphine titration is a pharmacological method
      which involves morphine boluses administration until pain relief, allowing a
      limitation in morphine side effects which are mainly dose dependent. I.v.
      morphine titration is widely used in prehospital care, emergency unit, PACU, ICU,
      and cancerology, in young and elderly patients. In the PACU, when the VAS (visual
      analogue scale) increases to more than 30 mm, i.v. morphine titration every five
      minutes with an unlimited number of 2 or 3 mg boluses provides an efficient
      analgesic regimen in adults. Titration is performed until pain relief (VAS < or
      =30), sedation that is the most frequent side effect during i.v. morphine
      titration (Ramsay score >1), severe side effects (like respiratory depression).
      CONCLUSION: Because of important pharmacological variability in morphine need, iv
      morphine titration is a simple method which allows a rapid and efficient pain
      relief notably in the postoperative care.

PMID- 15501628
TI  - [Clinical applications of intravenous anaesthetics pharmacology: the example of
      hypnotics and opioids].
AB  - OBJECTIVE: To review the general principles of pharmacokinetics and
      pharmacodynamics models by focusing on intravenous anaesthetics (hypnotics and
      opioids). DATA SOURCES: Medline references, lectures from the French congress of
      anaesthesiology and intensive care medicine, abstracts. DATA SYNTHESIS:
      Pharmacokinetic and pharmacodynamic modelling allows simple estimation of
      becoming of anaesthetic drugs in the body, instead of classical pharmacologic
      approach. However, pharmacokinetic as well as pharmacodynamic parameters are
      often considered as resulting from complex mathematic approaches and remain then
      poorly used in practice by physicians. The aim of this article is to simply
      expose concepts underlying PK-PD models building and to explain significance of
      the main PK-PD parameters (first-order rate constants, k(e0), T(1/2)k(e0),
      T(peak), context-sensitive half-time, context-sensitive decrement times).
      Clinical consequences for using intravenous anaesthetic drugs (hypnotics and
      opioids) are exposed either during bolus injection or continuous infusion, when
      injected alone or co-administered.

PMID- 15501629
TI  - [Pneumatic anti-shock garment use leading to non-visualization of pelvic arterial
      bleeding on angiography].
AB  - Initial reports of pneumatic anti-shock garment (PASG) in severely hypotensive
      patients appeared promising. Nevertheless, large-scale studies in prehospital
      settings have shown no overall reduction in mortality rates among hypotensive
      patients with application of the PASG. However, in a subsample of patients with
      blood pressure < or =50 mmHg, PASG seems to be useful to reduce bleeding and
      improve survival. To our knowledge, our case report is the first which directly
      showns on angiography the hemostatic effect of PASG on pelvic trauma bleeding. In
      spite of its possible complications, PASG remains one of the tools of trained
      trauma teams who regularly treated severe haemorrhagic shock.

PMID- 15501630
TI  - [Benefit of pharmaceutical anti-oedematous treatment in acute adult
      epiglottitis].
AB  - Acute adult epiglottitis is a potentially life threatening infectious and
      respiratory emergency as it may result in airway obstruction. Endotracheal
      intubation, if needed, is a highly risky option in this situation and responsible
      for important morbidity and mortality rate. The option of a pharmaceutical anti
      oedematous treatment, in order to avoid the risks involved in the endotracheal
      route has rarely been described. We here report the case of a 50-year-old man
      with a serious acute infectious epiglottitis who was treated at home by a Mobile
      Intensive Care Unit where a treatment of nebulized epinephrine and intravenous
      steroids was undoubtedly a successful option to the endotracheal route. So that,
      for adult patients and in the absence of any risk of an imminent respiratory
      arrest, this anti-oedematous treatment should be considered in order to avoid
      endotracheal route, an option which should be undertaken in case of
      complications. Nevertheless, this isolated case study concerning an adult is not
      transposable to children for which airway obstruction tolerance is lower.

PMID- 15501631
TI  - [Deep lactic acidosis after valproate self-poisoning].
AB  - A sixty-year-old woman was admitted in the ICU after Depamide (Valpromide) self
      poisoning (430 mg/kg). Four hours after the ingestion, the patient presented coma
      (Glagow coma score of 3) with bilateral mydriasis requiring tracheal intubation
      and mechanical ventilation, hypotension requiring epinephrine infusion (0.9
      microg/kg per minute), acidosis and hyperlactatemia (29.7 mmol/l at 12 hours)
      without any kidney or liver failure. The maximal serum valproic acid
      concentration measured was 342 mg/l after twelve hours (therapeutic rate: 35-85
      mg/l). A continuous infusion of sodium bicarbonate was associated with continuous
      venovenous haemodiafiltration. Progressive haemodynamic improvement and
      neurologic recovery leaded to extubation at 36 hours.

PMID- 15501632
TI  - [Regional anaesthesia for labor adn delivery in a parturient with neuropathy with
      liability to pressure palsy (tomaculous neuropathy)].
AB  - Tomaculous neuropathy (or hereditary neuropathy with liability to pressure palsy
      [HNLPP]) is a rare and hereditary disease which incidence has probably been
      underestimated. It is characterised by demyelination resulting in numbness and
      weakness after nerve pressure, injury or stretch. Despite a well-documented
      genetic pathophysiologic mechanism, implications for anaesthesia in patients with
      HNLPP are only speculative and the use of regional anaesthesia is debatable. We
      report here the case of a patient with HNLPP who was followed during two
      consecutive pregnancies in the same hospital and for whom an expert of the SOS-RA
      hotline service was consulted before each delivery. For the first delivery,
      epidural analgesia was performed for labour pain control but a caesarean section
      was necessary because of failure to progress (0.0625% bupivacaine with 0.2
      microg/ml sufentanil for labour then 2% lidocaine with adrenaline for surgery).
      Two years later, the patient was again seen for a preanaesthetic visit because
      elective Caesarean section was planned. Spinal anaesthesia using hyperbaric
      bupivacaine and sufentanil was used. Both deliveries were uneventful and there
      were no neurologic complaints in the postpartum periods.

PMID- 15501633
TI  - [An unusual biologic manifestation of the red man syndrome].

PMID- 15501634
TI  - Images in obstetric anesthesia: giant cystoadenofibroma in a healthy parturient.

PMID- 15501635
TI  - [Interest of naloxone infusion on analgesia and respiratory depression after
      spinal anaesthesia with morphine].

PMID- 15501637
TI  - The menopause transition.
AB  - The menopause transition is a period of life during which a series of dynamic
      changes in physiology are taking place. There seems to be a transient increase in
      symptoms of many types, which are occasionally severe. There is a
      disproportionate burden of morbidity that seems to accrue to women of high body
      mass index and low socioeconomic status. Moreover, there are ethnic differences
      in hormones and symptoms that may reflect either basic biologic variation in
      hormone receptors and actions or the different social milieu that women in
      different ethnic groups experience. Current medical management of the
      perimenopause should include screen-ing for general health maintenance, avoidance
      of weight gain, and a holistic approach to symptoms.

PMID- 15501638
TI  - Neuroendocrine physiology of the early and late menopause.
AB  - Hormonal integration of the reproductive system is dramatically affected by
      reproductive aging. The progressive loss of ovarian follicles with normal aging
      is accompanied by an initial decrease in inhibin B and a concomitant increase in
      follicle-stimulating hormone. Subsequently, inhibin A and progesterone decrease,
      where as estradiol levels are maintained and often increase. In the late
      reproductive stage, cycles remain regular whereas the early and late menopausal
      transition are characterized by irregular cycles and often dramatic swings in
      estradiol and gonadotropin levels. Studies in younger and older postmenopausal
      women suggest that there are age-related changes in the neuroendocrine axis that
      are independent of the changing ovarian hormonal milieu of the menopausal
      transition but may contribute to the end of reproductive life.

PMID- 15501639
TI  - Endocrine function of the postmenopausal ovary.
AB  - In light of recent evidence, it seems that the endocrine function of the
      postmenopausal ovary is more elusive and more variable than previously believed.
      Although the current authors believe that the postmenopausal ovary has lost a
      clinically significant estrogenic capability, a definitive conclusion regarding
      androgen production cannot be forthcoming.

PMID- 15501640
TI  - Acute consequences of the menopausal transition: the rise of common menopausal
      symptoms.
AB  - More than 80% of women experience psychologic or physical symptoms in the late
      reproductive years, with varying degrees of severity and disruption in their
      lives. Patients and clinicians have misconceptions about what changes are
      considered "normal" or"abnormal" during this period. Of importance to clinicians,
      large-scale longitudinal studies recently have been conducted to better
      characterize and explore changes during this period. This article re-views the
      current evidence regarding the acute symptoms of the menopausal transition,
      including vasomotor symptoms, mood changes, sleep problems, and changes in sexual
      functioning.

PMID- 15501641
TI  - Indications for hormone therapy: the post-Women's Health Initiative era.
AB  - Information from the Women's Health Initiative (WHI) trial has given physicians
      valuable tools for counseling women aged 50 to 79 years about the short-term
      risks of hormone therapy (HT). Unanswered questions remain, particularly on the
      risks and benefits of discontinuing HT among long-term users. The decision to
      discontinue HT should be carefully considered, because stopping and re-starting
      after several months may "reset the clock" for risks associated with changes in
      hepatic protein synthesis. The current authors recommend low-dose transdermal
      hormonal formulations,but no large-scale randomized trials exist to confirm the
      veracity of this recommendation. It has been suggested that starting HT in the
      menopausal transition would alleviate the HT risks observed withWHI. Until
      additional data are available to counsel women in the menopausal transition,
      however, the conservative counseling approach is to apply those figures available
      from the WHI, particularly because women aged 50 to 59 years using estrogen
      progestin therapy have an unfavorable risk-benefit ratio, similar to that seen in
      older women.

PMID- 15501642
TI  - The role of complementary and alternative medicine in management of menopausal
      symptoms.
AB  - There is a great need for alternatives to hormone therapy for use by symptomatic
      menopausal women. Alternatives to estrogen can en-compass lifestyle change,
      complementary and alternative medicine (CAM), and prescription nonhormonal
      therapies. The use of CAM therapies for menopausal symptoms is widespread and has
      been increasing. In recent years, there has been an increase in the quantity and
      quality of research related to CAM therapy use for menopausal symptoms. A highly
      effective and safe CAM therapy for menopausal symptoms would be valuable but has
      remained elusive to date. This article reviews randomized controlled trials
      examining the efficacy of CAM therapies for menopausal symptoms.

PMID- 15501643
TI  - Bone health and aging: implications for menopause.
AB  - Osteoporosis is one major health condition that contributes to excess morbidity
      and mortality in women after menopause. In the past, hormone therapy (HT) was
      prescribed commonly for symptoms of menopause, and there was also evidence that
      HT protected against osteoporosis. Recently, however, the overall health risks
      have been reported to exceed benefits, with the beneficial effects seen only in
      the decreased incidence of hip fractures and colon cancer. The role of HT in
      menopausal women is unclear at this time, although many women may require it to
      reduce menopausal symptoms. Osteoporosis may be an area where the benefit of
      using HT may outweigh the risks in a select group of women. Further, because
      lower than usual doses of estrogen have been shown to reduce menopausal symptoms
      and to protect bone, additional research will likely expand physicians' current
      knowledge of the use of HT in menopausal women. This article reviews the use of
      low-dose estrogen to promote bone health in postmenopausal women.

PMID- 15501644
TI  - Areas for future inquiry.
AB  - Osteoporosis, heart disease, and cancer remain worldwide challenges for women's
      health. This article discusses areas for future inquiry in these areas of
      research.

PMID- 15501645
TI  - The therapeutic role of estrogens in postmenopausal women.
AB  - This article reviews the history and present use of estrogens for the treatment
      of menopausal symptoms. It includes management of several different cases,
      including a review of all estrogens and estrogen/progestin preparations available
      in the United States.

PMID- 15501646
TI  - Nitrogen fixation in acidophile iron-oxidizing bacteria: the nif regulon of
      Leptospirillum ferrooxidans.
AB  - The Gram-negative iron-oxidizing bacterium Leptospirillum ferrooxidans contains
      all genes necessary for nitrogen fixation, from genes encoding the Mo-Fe
      nitrogenase, the specific regulator (nifA), global regulators like glnB and ntrC
      like genes, to other sensors and transport systems somehow related to nitrogen
      assimilation. We review current knowledge about the nif regulon and its
      connection with other metabolic functions in L. ferrooxidans.

PMID- 15501647
TI  - Comparative genomics and functional roles of the ATP-dependent proteases Lon and
      Clp during cytosolic protein degradation.
AB  - The general pathway involving adenosine triphosphate (ATP)-dependent proteases
      and ATP-independent peptidases during cytosolic protein degradation is conserved,
      with differences in the enzymes utilized, in organisms from different kingdoms.
      Lon and caseinolytic protease (Clp) are key enzymes responsible for the ATP
      dependent degradation of cytosolic proteins in Escherichia coli. Orthologs of E.
      coli Lon and Clp were searched for, followed by multiple sequence alignment of
      active site residues, in genomes from seventeen organisms, including
      representatives from eubacteria, archaea, and eukaryotes. Lon orthologs, unlike
      ClpP and ClpQ, are present in most organisms studied. The roles of these
      proteases as essential enzymes and in the virulence of some organisms are
      discussed.

PMID- 15501648
TI  - Cyanophage infection and photoinhibition in marine cyanobacteria.
AB  - Members of two cyanobacterial genera, Synechococcus and Prochlorococcus, are
      dominant within the prokaryotic component of the picophytoplankton and contribute
      significantly to global photosynthetic productivity. These organisms are known to
      be susceptible to infection by bacteriophages (viruses that infect bacteria) and
      it is believed that phage infection in the oceans has exerted selective pressures
      on the evolution of both phage and host and continues to influence community
      structure. Understanding of the processes of host-phage interaction within the
      marine environment is limited; however, new insights have arisen from sequence
      analysis of the genome of the bacteriophage S-PM2, which infects Synechococcus
      strains. The phage was found to encode homologs of the key photosystem II
      reaction center core polypeptides, D1 and D2. These reaction center polypeptides
      are known to be rapidly turned over in uninfected cells in a repair cycle that
      helps to protect oxygenic phototrophs against photoinhibition. This finding
      suggests that bacteriophages infecting marine cyanobacteria may play an active
      role in protecting their hosts against photoinhibition, thereby ensuring an
      energy supply for replication by preventing the deleterious effects on host cell
      integrity seen during acute photoinhibition.

PMID- 15501649
TI  - Survival and injury of Arcobacter after artificial inoculation into drinking
      water.
AB  - The aim of this work was to assess the effect of chlorine water treatment on
      Arcobacter butzleri and to study the survival strategies of this organism in
      chlorinated and non-chlorinated drinking water. A. butzleri NCTC 12481 was
      inoculated into chlorinated and non-chlorinated water and samples were removed
      aseptically, immediately and periodically during the next 2 days (for chlorinated
      drinking water) or 35 days (for non-chlorinated drinking water). The membrane
      integrity (Live/Dead BacLight kit), 16S rRNA (FISH technique), DNA content (23S
      rRNA PCR-RFLPs) and culturability changes in A. butzleri cells were analyzed.
      Culturability of the cells was lost at 5 min in chlorinated drinking water. At
      that time the cells showed membrane damage, although fluorescent intensity of 16S
      rRNA hybridization was constant throughout the chlorine treatment. After 48 h the
      amplicon specific for the 23S rRNA gene was weakly detected. In non-chlorinated
      drinking water cells lost their culturability after 16 days but the other factors
      measured indicated that Arcobacter remained viable throughout the experiment.

PMID- 15501650
TI  - Antiproliferative activity of Actinobacillus (Haemophilus) actinomycetemcomitans
      and Fusobacterium nucleatum in peripheral blood mononuclear cells.
AB  - Several studies indicate Actinobacillus (Haemophilus) actinomycetemcomitans and
      Fusobacterium nucleatum as etiologic agents of periodontal disease.
      Immunosuppressive factors produced by microorganisms probably contribute to the
      initiation and evolution of this disease. This study evaluated the
      antiproliferative activity of ammonium precipitate fractions of A. (H.)
      actinomycetemcomitans and F. nucleatum isolates from humans and marmosets both
      with and without periodontal disease. All A. (H.) actinomycetemcomitans and most
      F. nucleatum strains inhibited PBMC proliferation in a dose-dependent manner. The
      degree of cell proliferative inhibition of each bacterial species differed among
      the strains and was independent of host clinical status. The in vitro inhibition
      of stimulated lymphocyte proliferation induced by different A. (H.)
      actinomycetemcomitans and F. nucleatum isolates demonstrated the importance of
      this phenomenon in bacterial virulence, playing a possible suppressor role in
      host defense mechanisms in vivo. Moreover, our findings pointed out a marked
      difference between A. (H.) actinomycetemcomitans and F. nucleatum cytoplasmic
      extracts in their antiproliferative activity, regarding the antigen concentration
      required for maximum inhibition and their vulnerability to heating and
      proteolytic treatment.

PMID- 15501651
TI  - Species-specific PCR determination of Listeria seeligeri.
AB  - Listeria seeligeri is a non-pathogenic bacterium coming under the genus Listeria.
      As this bacterium resembles other Listeria species such as L. monocytogenes and
      L. ivanovii that are pathogenic to man and animals, it is important that rapid
      and precise identification techniques be available for L. seeligeri in cases
      where such determination is desirable. A specific molecular test on the basis of
      a uniquely present gene region in L. seeligeri will be of particular value under
      the circumstances. In this report, after comparative screening of genomic DNA
      from six Listeria species by dot blot hybridization, we isolated one L. seeligeri
      specific clone (lse24-315) that contains an insert of 1538 bp. Using primers
      (lse24-315F and lse24-315R) derived from this clone, we showed that a specific
      PCR product of 375 bp was generated from genomic DNA of L. seeligeri strains
      only, but not of other Listeria species or common bacteria. Therefore, the PCR
      employing primers lse24-315F and lse24-315R provides a rapid, sensitive and
      specific method for distinguishing L. seeligeri from other Listeria and common
      bacteria.

PMID- 15501652
TI  - Screening procedures for selecting rhizobacteria with biocontrol effects upon
      Fusarium verticillioides growth and fumonisin B1 production.
AB  - Screening is a critical step in the discovery of microbial agents that can exert
      biological control of Fusarium verticillioides at the root level. The objectives
      of this research were to determine the utility of a niche overlap index to
      realise the first screening of maize rhizobacterial isolates during different
      water activities. Studies were conducted to evaluate various methods for second
      screening with different modes of action. The antifungal activity of bacterial
      isolates through antibiosis assay was checked and the influence of different
      isolates on Fusarium verticilliodes growth and fumonisin B(1) was studied. Eleven
      competitive rhizobacterial isolates (Arthrobacter globiformis RC1, Azotobacter
      armeniacus RC2, A. armeniacus RC3, A. globiformis RC4, A. globiformis RC5, A.
      armeniacus RC6, Pseudomonas solanacearum RC7, Bacillus subtilis RC8, B. subtilis
      RC9, P. solanacearum RC10, B. subtilis RC11) were selected for the studies which
      followed. All bacteria were able to utilise the widest range of carbon sources
      and showed the highest niche overlap indices at the water activities tested. All
      bacterial antagonists reduced fumonisin B(1) production at all levels tested.
      Isolates belonging to Pseudomonas and Bacillus genera significantly inhibited
      fumonisin B(1) production, which ranged between 70 and 100%. Also, A. armeniacus
      RC2 caused important fumonisin B(1) reduction. The results of the present work
      suggest that A. armeniacus RC2, A. armeniacus RC3, B. subtilis RC8, B. subtilis
      RC9, B. subtilis RC11, P. solanacearum RC7, and P. solanacearum RC10 could have
      practical value in the control of F. verticillioides root colonisation. This
      paper is part of an on-going study to determine their application at the field
      level.

PMID- 15501653
TI  - Comparative evaluation of coagulase-negative staphylococci (CoNS) adherence to
      acrylic by a static method and a parallel-plate flow dynamic method.
AB  - The main goal of this work was to evaluate the adhesion to acrylic of several
      clinical strains of Staphylococcus epidermidis and Staphylococcus haemolyticus
      using both static and dynamic adhesion methods, and to compare the results
      obtained with these two methods. Adhesion was evaluated using the static slide
      method with different washing procedures, and the parallel plate flow chamber
      method. The extent of S. epidermidis adhesion, assessed by both methods, was
      greater than that of S. haemolyticus. The number of bacteria which adhered using
      the static method was lower than that using the dynamic method. It was found that
      the simple static method, when performed with an accurate washing procedure, can
      be as effective as the dynamic flow method for assessing differences in the
      adherence capacity of strains. Although the dynamic flow method yielded more
      overall information, its greater complexity and cost may not always justify its
      use for certain experimental comparisons. This investigation has shown that
      simple static adhesion methods, when performed accurately, can be used to
      evaluate differences in adhesion capacity.

PMID- 15501654
TI  - Aggregation-based cooperation during bacterial aerobic degradation of
      polyethoxylated nonylphenols.
AB  - Three bacterial strains were isolated from activated sludge samples of two
      treatment plants receiving domestic and industrial wastewaters containing
      polyethoxylated nonylphenols. One strain (VA160) was isolated on rich medium, and
      the other two (BCaL1 and BCaL2) on mineral medium containing two industrial
      mixtures of nonylphenol ethoxylates as the sole carbon source. Strain VA160 was a
      Gram-positive, spore forming, filamentous bacterium, producing aggregates during
      growth in liquid medium. On the basis of phylogenetic analysis the strains were
      assigned to the Bacillus (VA160), Acinetobacter (BCaL1) and Stenothrophomonas
      (BCaL2) genera. High performance liquid chromatography analysis showed that only
      the Acinetobacter and Stenothrophomonas strains were involved in the degradation
      of polyethoxylated nonylphenols. Bacillus VA160, however, when co-cultured with
      the two degrading strains, induced the formation of cell aggregates and
      facilitated NPEO degradation. Fluorescent in situ hybridisation on the activated
      sludge sample from which Bacillus VA160 was isolated, using probes for Gram
      positive bacteria with low G + C content, showed that bacteria belonging to this
      group specifically occurred inside the examined flocs. These observations suggest
      that the enhanced biodegradation of polyethoxylated nonylphenols in the three
      membered co-culture is favoured by VA160-induced aggregation of BcaL1 and BcaL2
      cells involved in the process.

PMID- 15501655
TI  - A novel genetic locus outside the symbiotic island is required for effective
      symbiosis of Bradyrhizobium japonicum with soybean Glycine max.
AB  - In order to investigate the symbiotic interaction between soybean and
      Bradyrhizobium japonicum, TnphoA mutagenesis of the microsymbiont was performed.
      Mutant strain 2-10 was found to induce a strongly reduced number of ineffective
      nodules. Ultrastructural analysis of the soybean nodule central tissue revealed
      the presence of numerous starch granules and vacuoles in the infected cells. In
      addition, the number of symbiosomes was extremely low, indicating an impaired
      interaction between the plant and invading bacteria. Cloning and sequencing of
      the mutated DNA region uncovered four open reading frames (ORFs) lacking any data
      base similarities. ORFs srrA1 and srrA2, the 2-10 TnphoA insertion site, are
      encoded in the same reading frame. A 35-kDa expression product in Escherichia
      coli indicated the presence of a common protein, called SrrA (symbiotically
      relevant region) in B. japonicum 110spc4, encoded by combined srrA1 and srrA2
      genes. The analysis of gene disruption mutants revealed that srrB and srrC were
      also required for effective symbiosis with soybeans. Further downstream the gene
      for a putative inner membrane protein (pipA) of unknown function was encoded on
      the opposite strand. Primer extension studies led to the conclusion that the
      organization of genes differed from the RhizoBase annotation in this particular
      region of B. japonicum USDA110.

PMID- 15501656
TI  - Genome-wide comparison reveals great inter- and intraspecies variability in B.
      pseudomallei and B. mallei pathogens.
AB  - Burkholderia mallei and B. pseudomallei, closely related Gram-negative bacteria,
      are causative agents of serious infectious diseases of humans and animals:
      glanders and melioidosis, respectively. Despite numerous studies of these
      pathogens, the detailed mechanism of their pathogenesis is still unknown. The
      problem is even more complicated due to natural variability of B. pseudomallei
      and B. mallei strains, the understanding of which is a prerequisite for rational
      design of tools for diagnostics, prophylaxis and therapy of the diseases. Using a
      subtractive hybridization technique, we compared the genomes of B. pseudomallei C
      141 and B. mallei C-5 strains. A subtracted library of DNA fragments specific for
      B. pseudomallei C-141 and absent from B. mallei C-5 was obtained and analyzed. A
      variety of differences have been detected and mapped on the recently sequenced
      genome of B. pseudomallei K96243. A comparative sequence analysis also revealed
      considerable genomic differences between B. pseudomallei C-141 and B. mallei ATCC
      23344 strains sequenced at The Institute for Genomic Research (TIGR). We also
      observed significant genomic differences between B. pseudomallei C-141 and B.
      pseudomallei K96243. Some of the differential DNA fragments displayed similarity
      to different mobile elements which have not yet been described for B.
      pseudomallei, whereas the others matched various prophage components, components
      of active transport systems, different enzymes and transcription regulators. A
      substantial proportion of the differential clones had no database matches either
      at the nucleotide or protein level. The results provide evidence for great genome
      wide variability of B. pseudomallei, further confirmed by Southern blot analysis
      of various B. pseudomallei strains. The data obtained can be useful for future
      development of efficient diagnostic tools allowing rapid identification of
      species, strains and isolates of B. mallei and B. pseudomallei.

PMID- 15501657
TI  - Inferring pathogen inactivation from the surface temperatures of compost heaps.
AB  - A sufficiently high composting temperature should inactivate many common
      pathogens likely to be present in solid animal waste. Monitoring core
      temperatures inside compost heaps is not straightforward, which means that heaps
      are not generally monitored. An alternative is to monitor surface temperatures
      and use those data to infer core temperatures, and thus whether pathogen
      inactivation has occurred. This paper describes two methods (thermal imaging and
      thermocouples) for the measurement of surface temperature, and a modelling
      approach using time series analysis to predict the temperatures obtained in the
      core of aerated heaps of composting pig farmyard manure (FYM) from surface
      temperature data. The model was able to predict core temperatures in the heap
      quite closely for a period of time for well insulated parts of the heap, although
      predictions were further from observed values close to the surface of the heap
      and the aeration pipe.

PMID- 15501658
TI  - Rheological properties of dairy cattle manure.
AB  - Rheological properties are important for the design and modelling of handling and
      treating fluids. In the present study, the viscosity of liquid manure (about 10%
      total solids) was measured at different shear rates (2.38-238 s(-1)). The effect
      of temperature on the viscosity at different shear rates was also studied. The
      results showed that manure has non-Newtonian flow properties, because the
      viscosity strongly depended on the applied shear rate. The results showed also
      that manure behaves like real plastic materials. The power-law model of the shear
      stress and the rate of shear showed that the magnitude of the consistency
      coefficient decreased while increasing the temperature, with high values of the
      determination coefficient. Moreover, the results showed that the Arrhenius-type
      model fitted the temperature effect on manure viscosity very well (R2 at least
      0.95) with calculated activation energy of 17.0+/-0.3 kJ mol(-1).

PMID- 15501659
TI  - Comparative culturing of Pleurotus spp. on coffee pulp and wheat straw: biomass
      production and substrate biodegradation.
AB  - The results of the cultivation of six strains of Pleurotus (P. djamor (2), P.
      ostreatus (2) and P. pulmonarius (2)) on coffee pulp and wheat straw are
      presented. Metabolic activity associated with biomass of each strain was
      determined, as well as changes in lignin and polysaccharides (cellulose and
      hemicellulose), phenolic and caffeine contents in substrate samples colonized for
      a period of up to 36 days. Analysis were made of changes during the mycelium
      incubation period (16 days) and throughout different stages of fructification.
      Greater metabolic activity was observed in the wheat straw samples, with a
      significant increase between 4 and 12 days of incubation. The degradation of
      polysaccharide compounds was associated with the fruiting stage, while the
      reduction in phenolic contents was detected in both substrates samples during the
      first eight days of incubation. A decrease was observed in caffeine content of
      the coffee pulp samples during fruiting stage, which could mean that some
      caffeine accumulates in the fruiting bodies.

PMID- 15501660
TI  - Upgrading of liquid fuel from the pyrolysis of biomass.
AB  - Pyrolysis of biomass was carried out in a fluidized bed unit (5 kg/h) with the
      objective of maximizing liquid yield. Liquid product formed in pyrolysis was
      separated into two phases: water phase and oil phase. The oil phase was upgraded
      by sulfided Co-Mo-P catalyst in an autoclave. Effects of reaction conditions on
      the product distribution were investigated, and optimal conditions were therefore
      concluded. Comparison was made by analysis between the raw oil phase and the
      upgraded liquid fuel. The significant difference between the raw pyrolytic oil
      and the upgraded oil was that the former was methanol-soluble while the latter
      was oil-soluble.

PMID- 15501661
TI  - New lubricants from vegetable oil: cyclic acetals of methyl 9,10
      dihydroxystearate.
AB  - Potential new lubricants and fuel lubricity enhancers have been prepared from
      methyl 9,10-dihydroxystearate and long chain aldehydes to form the corresponding
      cyclic acetals. These materials are oils down to low temperatures, as compared to
      symmetric ketals derived from the same diol, which are waxes at room temperature.
      The acetals form in an equilibrium reaction (Keq approximately 60) which suggests
      they will be stable as fuel additives. The viscosities of the new oils are close
      to those predicted for normal paraffins with the same number of non-hydrogen
      atoms, but the acetal structure has subtle effects on viscosity as compared to
      branched alkanes. Acetals with long alkyl branches maintain higher viscosity on a
      molecular weight basis compared to branched alkanes. The qualitative relationship
      between branch length and viscosity is discussed. These acetals are potential
      candidates for novel biobased lubricants.

PMID- 15501662
TI  - Compost liquor bioremediation using waste materials as biofiltration media.
AB  - Compost liquor results from the percolation of precipitation through composting
      waste; the release of liquids from high moisture content feedstocks; and as a
      result of runoff from hard surfaces and machinery. This research aimed to
      establish the potential for waste materials to act as media for low-cost compost
      liquor biofilters. Six types of potential biofilter media were packed into
      experimental biofilters (1 m long x 0.11 m diameter) and irrigated with compost
      liquor (organic loading rate of 0.6 kg/m3/d) for three months. The pH, BOD5,
      NH3/NH4+, and phytotoxicity of the effluent was monitored regularly. Natural,
      organic materials (oversize, compost and wood mulch) performed best, when
      compared to synthetic materials such as polystyrene packaging or inert materials
      such as broken brick. On average, the best media achieved 78% removal of both
      BOD5 and ammoniacal nitrogen during the study period. Although significant
      improvements in liquor quality were achieved, the effluent remained heavily
      polluted.

PMID- 15501663
TI  - Alfalfa as a single dietary source for molt induction in laying hens.
AB  - Molting is a process by which a hen's reproductive tract is rejuvenated prior to
      the beginning of a laying cycle. This process is often artificially induced in
      commercial settings in order to extend the productive life of a flock of hens.
      The most common method for the induction of molt is feed withdrawal for a period
      of several days. It has been noted that feed withdrawal, while effective in
      inducing molt and allowing an adequate reproductive rest period for the hen, may
      cause deleterious effects on the animal. This has prompted the investigation of
      alternatives to feed deprivation for the induction of molt in commercial laying
      hens. This study involved feeding alfalfa to hens to assess its ability to induce
      molt. Results show that alfalfa meal and alfalfa pelleted diets were equally
      effective as feed withdrawal in causing ovary weight regression in birds. Molted
      hens induced by alfalfa diets exhibited postmolt levels of egg production over a
      twelve week period that were similar to that of hens molted by feed withdrawal.
      The postmolt eggs laid by hens molted by alfalfa were of comparable quality to
      eggs from feed deprived hens. Alfalfa, a fibrous feed with low metabolizable
      energy, may be provided to hens on an ad libitum basis for an effective molt
      induction that retains comparable egg quality and production.

PMID- 15501664
TI  - Comparison of a static gravity screen-roll press combination separator to a PAM
      assisted gravity belt thickener system for swine waste slurry solids separation.
AB  - Liquid effluent resulting from solids separation from raw swine slurry (RS) using
      a static gravity screen-roll press separator (SE) and a polyacrylamide (PAM)
      flocculant-assisted gravity belt thickener system (BE1 and 2, with BE2
      designating an added belt thickening of SE) were compared. Effluent pH was 7.6
      7.7. Dissolved oxygen was less than 0.01 mg/l in RS and SE and 0.50 mg/l in BE1
      and 2. Solids dry weight and total phosphorus concentrations were reduced
      significantly (p0.05) in SE (17-27%) and in BE1 and 2 (92-96%), relative to RS.
      Phosphorus concentration reductions were higher than those previously found.
      Settleable and suspended solids, total nitrogen and chemical oxygen demand were
      significantly reduced in BE1 and 2 (63-99%). No significant differences (p>0.05)
      were found between BE1 and 2. Results indicated that the gravity belt thickener
      system was more efficient at solids separation than the screen-roll press system.

PMID- 15501665
TI  - Treatment of strong domestic sewage in a 96 m3 UASB reactor operated at ambient
      temperatures: two-stage versus single-stage reactor.
AB  - A 96 m3 UASB reactor was operated for 2.5 years under different conditions to
      assess the feasibility of treating strong sewage (COD(tot) = 1531 mg/l) at
      ambient temperatures with averages of 18 and 25 degrees C for winter and summer
      respectively. During the first year, the reactor was operated as a two-stage
      system at OLRs in the range of 3.6-5.0 kg COD/m3 d for the first stage and 2.9
      4.6 kg COD/m3 d for the second stage. The results of the first stage showed
      average removals of 51% and 60% for COD(tot) and COD(ss) respectively without
      significant effect of temperature. The second stage reactor was unstable. The
      temperature affected sludge stabilization. During the second year, the first
      stage was operated as a single-stage UASB reactor at half of the previous loading
      rates. The results showed an average removal efficiency of 62% for COD(tot)
      during summer, while it dropped to 51% during wintertime. However, the effluent
      suspended solids were stabilized with VSS/TSS ratio around 0.50 all over the
      year. The sludge in the single-stage reactor was well-stabilized and exerted an
      excellent settlability. During the last three months of research, sludge was
      discharged regularly from the single-stage UASB reactor. The results showed no
      significant improvement in the performance in terms of COD(tot). Based on the
      results of the experiment, a single-stage UASB reactor operated at relatively
      long HRT is preferred above two-stage system at the Jordanian conditions.

PMID- 15501666
TI  - Isolation of Salmonella spp. from liquid and solid excreta prior to and following
      ensilage in ten swine farms located in central Mexico.
AB  - A study was carried out to define selected bacteriological characteristics of
      residues from 10 swine farms, 5 with or without prior clinical enteric disease
      (PCED) and to determine the effect of ensilage on the bacteria present in the
      solid fraction. At each farm, samples were taken from the sedimentation basin
      (SB), the solid fraction (SF), and the liquid fraction (LF). For each sample,
      CFU/g for enteric bacteria were quantified; Salmonella spp. were isolated and
      typified. Solid phase samples from each farm were used to prepare the ensilage,
      with a mixture of solids (80%), sorghum (12%) and molasses (8%). The quantity of
      enteric bacteria was significantly greater in farms without PCED (P < 0.05).
      Salmonella enterica were isolated from 8/10 of the farms with and without PCED;
      in 8 from SB; in 6 from LF; and in 5 from SF. Enteric bacteria were not isolated
      from silage, therefore, ensilage may be an alternative treatment for excreta that
      allows the elimination of pathogens such as Salmonella spp.

PMID- 15501667
TI  - Use of pruning waste compost as a component in soilless growing media.
AB  - The objective of this work was to study the use of pruning wastes compost (PWC)
      as a growing media component for ornamental plants. The main physical, chemical
      and biological characteristics of PWC were analysed in order to evaluate its
      suitability for use in soil-less cultivation. Six growth substrates were prepared
      by mixing PWC with peat (P), ground leaves (GL), sand (S) and spent mushroom
      compost (SMC) in different proportions. Two different pot experiments were
      carried out to test its characteristics of production using perennial ryegrass
      (Lolium perenne L.) and cypress (Cupressus sempervirens L.) as indicators and the
      different media as treatments. The growth experiments showed that PWC required
      mixing with a nutrient-richer material to produce higher results. Therefore,
      substrates containing SMC (PWC+P+SMC and PWC+SMC) seems to be the most adequate
      growing media. After the statistical analysis, we concluded that the PWC could be
      used as a growing media component.

PMID- 15501668
TI  - The use of smoke acid as an alternative coagulating agent for natural rubber
      sheets' production.
AB  - A comparative study of rubber sheets obtained using formic, acetic, and smoke
      acid as coagulants is shown for latex obtained from native Amazonian trees and
      also from commercial cultivated trees. The evaluation of both processes of
      coagulation was carried out by spectroscopic and physical-chemical analysis,
      showing no differences in the rubber sheets obtained. This new method of rubber
      sheet preparation was introduced into Amazonian rainforest rubber tapper
      communities, which are actually producing in large scale. The physical-mechanical
      properties were similar among a large sheets made by different rubber tapper
      communities using this new method.

PMID- 15501669
TI  - Solubility of multi-component biodiesel fuel systems.
AB  - Solubility of biodiesel fuel components in fossil diesel fuel-methanol-rapeseed
      oil methyl ester, fossil diesel fuel-ethanol-rapeseed oil methyl ester and fossil
      diesel fuel-ethanol-rapeseed oil ethyl ester systems was investigated. The
      solubility of components in the fossil diesel fuel-ethanol-rapeseed oil methyl
      ester system at 20 degrees C was substantially higher than in the fossil diesel
      fuel-methanol-rapeseed oil methyl ester system. The solubility of components in
      the fossil diesel fuel-ethanol-rapeseed oil ethyl ester system was slightly lower
      than in the fossil diesel fuel-ethanol-rapeseed oil methyl ester mixture. The
      moisture content of ethanol had a great influence on mixture solubility. With
      decrease of temperature, the solubility of components in the fossil diesel fuel
      ethanol-rapeseed oil methyl ester system decreased.

PMID- 15501670
TI  - Biocatalysis using an organic-soluble enzyme for the preparation of poly(lactic
      acid) in organic solvents.
AB  - Proleather from Bacillus sp. was chemically modified with decanoyl chloride for
      enhanced activity for the preparation of poly(lactic acid) in organic solvents.
      The modified enzyme was highly soluble (up to 44 mg-protein/ml) and active in
      various organic solvents including chloroform, tetrahydrofuran (THF), pyridine
      and acetone. The organic-soluble proleather efficiently catalyzed the
      polymerization of ethyl lactate. The reaction rate was 4-22 times that of native
      proleather, depending upon the solvent applied. The solubilized enzyme showed a
      highest activity at 50 degrees C, the same optimum temperature for both the
      native proleather and an immobilized enzyme, Novozyme-435. Denaturation of the
      enzymes' protein structures appeared to be the critical factor regulating the
      optimum activity temperature. Differential scanning calorimetry (DSC) analyses of
      the enzymes showed endothermic peaks around 55 degrees C, indicating the
      proteins' structures altered in that temperature range. Interestingly, the
      activity of the solubilized enzyme showed a more complicated water dependence as
      compared to native proleather.

PMID- 15501671
TI  - Characterization of a thermoalkalophilic esterase from a novel thermophilic
      bacterium, Anoxybacillus gonensis G2.
AB  - Poly-3-hydroxybutyrate (P3HB) degradation capabilities of a novel bacterium,
      Anoxybacillus gonensis G2, were investigated. Both changes on film surfaces of
      the solution-cast films monitored by scanning electron microscopy (SEM) and
      weight loss up to 24% after 72 h exposure to A. gonensis G2 cultures indicated
      secretion of an active esterase responsible for the degradation of P3HB films.
      Kinetic parameters, Vmax and Km for the esterase activity of crude enzyme from A.
      gonensis G2 in the presence of p-nitrophenylbutyrate as substrate were observed
      as 50 U/L and 0.125 mM, respectively, in 50 mM phosphate buffer, pH 7.5 at 60
      degrees C. The stimulation of the activity by Ca2+ is an evidence for the
      requirement of Ca2+ as a cofactor for the enzyme activity which is a
      characteristic for lipases/esterases. Inhibition of the esterase activity by
      metal chelating agents such as ethylenediamine tetraacetate, azide and cyanide
      has also supported the requirement of a metal ion for the activity. The thermal
      and pH stability profiles for the enzyme showed that the thermophilic bacterium
      A. gonensis G2 secretes an extracellular thermoalkalophilic PHB depolymerase
      active at 60 degrees C, and stable at this temperature for 120 min at pH 7.5 and
      for 24 h at pH 7.5-9.5 range at 4 degrees C by retaining over 75% of its initial
      activities.

PMID- 15501672
TI  - Effects of alkalinity and co-substrate on the performance of an upflow anaerobic
      sludge blanket (UASB) reactor through decolorization of Congo Red azo dye.
AB  - The effect of substrate (glucose) concentrations and alkalinitiy (NaHCO3) on the
      decolorization of a synthetic wastewater containing Congo Red (CR) azo dye was
      performed in an upflow anaerobic sludge blanket (UASB). Color removal
      efficiencies approaching 100% were obtained at glucose-COD concentrations varying
      between 0 and 3000 mg/l. The methane production rate and total aromatic amine
      (TAA) removal efficiencies were found to be 120 ml per day and 43%, respectively,
      while the color was completely removed during glucose-COD free operation of the
      UASB reactor. The complete decolorization of CR dye under co-substrate free
      operation could be attributed to TAA metabolism which may provide the electrons
      required for the cleavage of azo bond in CR dye exist in the UASB reactor. No
      significant differences in pH levels (6.6-7.4), methane production rates (2000
      2700 ml/day) and COD removal efficiencies (82-90%) were obtained for NAHCO3
      concentrations ranging between 550 and 3000 mg/l. However, decolorization
      efficiency remained at 100% with decreasing NaHCO3 concentrations as low as 250
      mg/l in the feed. An alkalinity/COD ratio of 0.163 in the feed was suggested for
      simultaneous optimum COD and color removal.

PMID- 15501673
TI  - Vinculin--a dynamic regulator of cell adhesion.
AB  - The ability of cells to tightly adhere to one another and to the extracellular
      matrix is fundamentally important in numerous biological processes, including
      embryogenesis, wound healing and maintenance of tissue integrity. Vinculin, a
      protein localized at the cytoplasmic face of cell-matrix and cell-cell adhesions,
      is required for strong cell adhesion. Two new crystal structures reveal that
      vinculin exhibits a high degree of structural plasticity upon ligand binding that
      might promote rapid changes in cell adhesion.

PMID- 15501674
TI  - RAP--a putative RNA-binding domain.
AB  - A novel approximately 60-residue domain has been identified in Homo sapiens
      MGC5297 and various other proteins in eukaryotes. Sequence searches reveal that
      the domain is particularly abundant in apicomplexans and is predicted to be
      involved in diverse RNA-binding activities.

PMID- 15501675
TI  - Actin-binding proteins--a unifying hypothesis.
AB  - Actin participates in more protein-protein interactions than any other known
      protein, including the interaction of actin with itself to form the helical
      polymer F-actin. The vast majority of actin-binding proteins (ABPs) can be
      grouped into conserved families. Only a handful of structures of complexes of
      actin with ABPs have been determined so far. These structures are starting to
      reveal how certain ABPs, including gelsolin, vitamin D-binding protein and
      Wiskott-Aldrich syndrome protein (WASP)-homology domain-2-related proteins, share
      a common actin-binding motif. It is proposed here that other ABPs, including
      actin itself, might share this motif, providing a mechanism whereby ABPs and
      actin compete for a common binding site. Of particular interest is a hydrophobic
      pocket that mediates important interactions in five of the existing structures of
      actin complexes. As the pocket remains accessible in F-actin, it is proposed that
      this pocket represents a primary target for F-actin-binding proteins, such as
      calponin-homology-related proteins and myosin.

PMID- 15501676
TI  - Interactions between BRCT repeats and phosphoproteins: tangled up in two.
AB  - The C-terminal region of the breast-cancer-associated protein BRCA1 contains a
      pair of tandem BRCA1 C-terminal (BRCT) repeats that are essential for the tumour
      suppressor function of the protein. Similar repeat sequences have been identified
      in many proteins that seem to mediate cellular mechanisms for dealing with DNA
      damage. The BRCT domain in BRCA1 has been recently shown to constitute a module
      for recognizing phosphorylated (phospho-) peptides, with a recognition groove
      that spans both BRCT repeats. The fact that many other BRCT-containing proteins
      have phospho-peptide binding activity suggests that BRCT repeats might mediate
      phosphorylation-dependent protein-protein interactions in processes that are
      central to cell-cycle checkpoint and DNA repair functions.

PMID- 15501677
TI  - Beginnings of a signal-transduction pathway for bioenergetic control of cell
      survival.
AB  - Two integral components of cellular transformation are increased cellular
      metabolism and apoptotic resistance. Recent progress in understanding the
      cellular functions of core apoptotic components and of growth factor-induced
      apoptotic regulatory proteins has indicated that the control of cellular
      metabolism and apoptosis are intertwined. There is growing evidence for
      connections between the regulation of both cellular bioenergetics and apoptosis
      and, thus, it is intriguing to explore the idea that growth factor regulation of
      cellular metabolism can directly affect cell survival.

PMID- 15501678
TI  - Protein unfolding in the cell.
AB  - Protein unfolding is an important step in several cellular processes such as
      protein degradation by ATP-dependent proteases and protein translocation across
      some membranes. Recent studies have shown that the mechanisms of protein
      unfolding in vivo differ from those of the spontaneous unfolding in vitro
      measured by solvent denaturation. Proteases and translocases pull at a substrate
      polypeptide chain and thereby catalyze unraveling by changing the unfolding
      pathway of that protein. The unfoldases move along the polypeptide chains of
      their protein substrates. The resistance of a protein to unfolding is then
      determined by the stability of the region of its structure that is first
      encountered by the unfoldase. Because unfolding is a necessary step in protein
      degradation and translocation, the susceptibility of a substrate protein to
      unfolding contributes to the specificity of these pathways.

PMID- 15501679
TI  - Instant decisions: transcription-independent control of death-receptor-mediated
      apoptosis.
AB  - Transcription-independent modulation of signaling mediated by death receptors
      (DRs) has emerged as an important determinant of cell survival during both
      development and cellular homeostasis. Frequently, a given DR signal must be
      redirected rapidly either to inhibit or to potentiate the apoptotic response.
      This process requires immediate, protein-synthesis-independent modifications of
      the regulatory molecules involved. Numerous mechanisms have been shown to
      regulate DR responses without engaging the apoptosis-directing transcription
      machinery. These mechanisms involve key posttranslational modifications such as
      phosphorylation, ubiquitination and proteolytic degradation, all of which affect
      the activities of proteins at different levels in the DR signaling pathways.
      Changes in the organization of regulatory molecules and in their interactions
      with other factors also affect the DR signaling pathways. The balance between
      these modulatory signals rapidly decides the fate of a cell.

PMID- 15501680
TI  - The biochemical response of the heart to hypertension and exercise.
AB  - Mechanical stress on the heart can lead to crucially different outcomes. Exercise
      is beneficial because it causes heart muscle cells to enlarge (hypertrophy).
      Chronic hypertension also causes hypertrophy, but in addition it causes an
      excessive increase in fibroblasts and extracellular matrix (fibrosis), death of
      cardiomyocytes and ultimately heart failure. Recent research shows that
      stimulation of physiological (beneficial) hypertrophy involves several signaling
      pathways, including those mediated by protein kinase B (also known as Akt) and
      the extracellular-signal-regulated kinases 1 and 2 (ERK1/2). Hypertension, beta
      adrenergic stimulation and agonists such as angiotensin II (Ang II) activate not
      only ERK1/2 but also p38 and the Jun N-terminal kinase (JNK), leading to
      pathological heart remodeling. Despite this progress, the mechanisms that
      activate fibroblasts to cause fibrosis and those that differentiate between
      exercise and hypertension to produce physiological and pathological responses,
      respectively, remain to be established.

PMID- 15501681
TI  - The power of two: protein dimerization in biology.
AB  - The self-association of proteins to form dimers and higher-order oligomers is a
      very common phenomenon. Recent structural and biophysical studies show that
      protein dimerization or oligomerization is a key factor in the regulation of
      proteins such as enzymes, ion channels, receptors and transcription factors. In
      addition, self-association can help to minimize genome size, while maintaining
      the advantages of modular complex formation. Oligomerization, however, can also
      have deleterious consequences when nonnative oligomers associated with pathogenic
      states are generated. Specific protein dimerization is integral to biological
      function, structure and control, and must be under substantial selection pressure
      to be maintained with such frequency throughout biology.

PMID- 15501682
TI  - Electrophysiological recording of deep tendon reflexes: normative data in
      children and in adults.
AB  - OBJECTIVE: Latency measurement of myoelectric deep tendon (T) reflex responses is
      not usually performed in EMG laboratories. We investigated the optimal conditions
      of reliable recording of T reflex in children and adults. METHODS: Two hundred
      and sixty-eight normal subjects (139 males, 129 females, age rank 2 days-80
      years) were studied. T reflexes were recorded from soleus and rectus femoris
      muscles (children and adults) and from triceps brachialis, biceps brachialis and
      flexor carpi radialis (adults). Specially devised hammers were used. They were
      fitted with a spring switch system in order to trigger the trace display on the
      EMG machine. Distinct technical options for the synchronisation delay assessment
      were tested. The nerve conduction velocities along reflex pathways were computed
      by referring the T wave latencies to subject's height. RESULTS: Reliable
      recordings could be obtained in all cases, with a strong linear correlation of
      the response latency with height. T reflex conduction velocities increased as the
      log value of subject age. Normative data from birth to 80 years are provided.
      CONCLUSION: T reflex recording represents a painless and easily performed
      technique. It may be helpful for the assessment of proximal conduction
      velocities, especially in children during maturation of the peripheral nervous
      system.

PMID- 15501683
TI  - Low-frequency repetitive TMS of premotor cortex can reduce painful axial spasms
      in generalized secondary dystonia: a pilot study of three patients.
AB  - Dystonia is associated with excessive corticospinal motor output. Motor cortex
      excitability may be reduced by low-frequency repetitive transcranial magnetic
      stimulation (rTMS) of premotor cortical areas. We report the effects of 1 Hz rTMS
      applied at 90% of resting motor threshold over the left premotor cortex in an
      open pilot study of three patients with severe, generalized, secondary dystonia
      including painful spasms in the proximal and axial musculature. A 20-min session
      of premotor rTMS was daily performed during 5 consecutive days. The series of
      rTMS sessions dramatically reduced the painful spasms, for 3-8 days after the
      last session, without any other significant beneficial effects. However, a slight
      reduction of the Movement score of the Burke, Fahn and Marsden rating scale was
      observed for two patients, and of the Disability score for the third one. Low
      frequency rTMS of the premotor cortex may improve some specific motor symptoms in
      severe, generalized dystonia. These results should prompt confirmation in a
      larger placebo-controlled study.

PMID- 15501684
TI  - Spastic paretic hemifacial contracture (SPHC) in a patient with multiple
      sclerosis. A clinical, EMG and neuroimaging study.
AB  - We present the case of a 42-year-old woman with a 4-year history of definite
      multiple sclerosis (MS) and sustained contracture of the left hemiface with
      marked left deviation of the nose, deepened left nasolabial groove, narrowed
      palpebral fissure and weakness of the contracting muscles. Needle
      electromyography showed continuous resting activity of irregularly firing motor
      unit potentials (MUP) in the left orbicularis oculi (OO) and orbicularis oris,
      but not in the left frontalis. Simultaneous recording of maximal voluntary
      contraction of the OO on both sides showed marked preponderance on the right.
      Blink reflex findings were consistent with an injury in the pons, mainly in the
      vicinity of the left facial nucleus. A magnetic resonance imaging study showed
      multiple supra- and infra-tentorial white matter lesions, as well as multiple
      lesions at the level of the pons. Complete recovery was observed after 3 months.
      This condition has been described in cases of brainstem tumor as spastic paretic
      hemifacial contracture (SPHC). Up to now SPHC has not been explicitly associated
      with MS and, in this case, it could be arguably attributed to hyperexcitability
      of the facial neurons due to demyelination of the corticofacial fibers.

PMID- 15501685
TI  - Bilateral vs. unilateral electromyographic examination of the external anal
      sphincter muscle.
AB  - AIM OF THE STUDY: In patients with cauda equina or conus medullaris lesions,
      bilateral electromyographic (EMG) examination of the subcutaneous external anal
      sphincter (EAS) muscles has been suggested. In spite of its circular shape, EAS
      should be considered as two separate semicircular muscles. The aim of the present
      study was to test the hypothesis that information obtained by bilateral
      examination of the EAS muscle outweighs inconvenience due to additional needle
      insertions. PATIENTS AND METHODS: A group of 67 patients with clinical and
      radiological data supportive of cauda equina or conus medullaris lesion was
      studied. From the subcutaneous EAS muscles motor unit potentials (MUPs) were
      sampled by the standard concentric EMG needle electrode, and an advanced EMG
      system with template operated multi-MUP analysis. Severity of EMG abnormalities
      was determined, and compared in 48 pairs of the left/right subcutaneous EAS
      muscles. RESULTS: In 18 patients, bilateral EMG abnormalities were found, in five
      of them asymmetry of involvement was demonstrated. Unilateral MUP abnormalities
      were found in 22 patients. The sensitivity of unilateral EMG analysis was 57% and
      of bilateral examination, 83%. CONCLUSION: In patients with suspected cauda
      equina lesions, as a rule, bilateral EMG of the subcutaneous EAS muscle is
      recommended.

PMID- 15501686
TI  - Lack of correlation between sternocleidomastoid and scalene muscle fatigability
      and duration of symptoms in chronic neck pain patients.
AB  - AIMS OF THE STUDY: Despite the evidence of greater fatigability of the
      superficial cervical flexor muscles in neck pain patients, the relationship
      between duration of neck pain and muscle fatigue has not been investigated. This
      study examined the relationship between myoelectric manifestations of
      sternocleidomastoid (SCM) and anterior scalene (AS) muscle fatigue and duration
      of neck pain in a group of patients with chronic neck pain. MATERIALS AND
      METHODS: Twenty chronic neck pain patients with a history of pain ranging between
      1 and 25 years (mean 6.15, S.D. 5.48 years) participated in this study.
      Myoelectric signals were recorded from the SCM and AS muscles from the side of
      greatest pain as patients performed sustained sub-maximal isometric cervical
      flexion contractions at 25% and 50% of the maximum voluntary contraction (MVC).
      The initial value and slope of the mean frequency (MNF), average rectified value
      (ARV) and conduction velocity (CV) of the EMG signals were calculated.
      Correlation analysis was applied to determine whether a relationship existed
      between the duration of neck pain and estimates of EMG variables. RESULTS AND
      CONCLUSIONS: No significant correlation was found between duration of pain and
      estimates of the MNF, ARV and CV for either SCM or AS contracting at 25% and 50%
      MVC. The length of history of neck pain does not appear to correlate with the
      extent of SCM and AS muscle fatigability in patients with chronic neck pain. This
      finding may be due to an increase of muscle fatigability occurring within the
      first few years of neck pain, which is not followed by signs of increased fatigue
      after this time. This was supported by the finding of significant correlations
      between duration of pain and AS fatigability on a subgroup of patients with pain
      duration less than 5 years. Future studies are warranted to examine how early
      signs of cervical muscle fatigability are evident after the onset of neck pain as
      this will have implications for rehabilitation.

PMID- 15501687
TI  - [Effect of an early visual encoding defect on attentional function: a study of
      daltonism using the Stroop test].
AB  - The Stroop color-word test is often used to assess attentional function. In this
      study we investigated whether dyschromatopsia affects the results of this test,
      and in that case which are the attentional consequences of this color-vision
      trouble. Event-related potentials were recorded on 19 dyschromatopsic subjects
      when submitted to a video-displayed Stroop test, and compared to those of 19
      control subjects. Results showed that reaction times of dyschromatopsic subjects,
      although generally longer than those of controls, had normal interference and
      facilitation effects. Potentials evoked by neutral stimulations were delayed for
      P2 and P3 waves, and those evoked by word-containing stimulations showed delays
      for N2b (N320) and P3 waves. The premotor potential appeared modified in
      dyschromatopsic patients, whereas error negativities, or correct response
      negativities were identical to those of control subjects. We conclude that
      dyschromatopsia affects negatively the performance in the Stroop test, at sensory
      levels which are reflected by evoked potentials, but without important
      consequences on attentional function. In particular, dyschromatopsia did not
      alter significantly the attentional focusing on the chromatic aspects of the
      stimulus.

PMID- 15501688
TI  - [Emergency EEG: actual indications and results].
AB  - PURPOSE: The indications of emergency electroencephalogram (eEEG) were defined by
      a French consensus conference in May 1996. We retrospectively confronted the
      recommendations with the actual requests for emergency EEG in our University
      hospital, in order to determine the contribution of the eEEG in the most frequent
      clinical situations encountered. MATERIAL AND METHOD: Three hundred and twenty
      nine consecutive eEEGs over a 6-months period were retrospectively analyzed.
      RESULTS AND CONCLUSION: The most frequent indications were presumption of brain
      death (13%), convulsive status epilepticus after treatment (12.1%), and suspicion
      of nonconvulsive epilepticus status (10.6%). More than one third of the requests
      (38.6%) were not in conformity with the recommendations of the consensus
      conference. The contribution of the EEG is much improved by the application of
      the consensual criteria. Thus, the EEG remains essential for the management of
      convulsive status epilepticus after treatment, to seek a subtle epilepticus
      status or a nonconvulsive epilepticus status. Conversely, the EEG did not prove
      useful in emergency after a transient loss or alteration of consciousness or a
      focal, non-febrile, neurological transient or permanent deficit.

PMID- 15501689
TI  - [Epileptic seizures in non-ketotic hyperglycemia].
AB  - Seizures are common in hyperglycemia and are often the first manifestation
      particularly in non-ketotic hyperglycemia (NKH). Published reports emphasize
      partial motor seizures almost exclusively. Here we present the clinical,
      biological and electrophysiological features of 22 consecutive patients with NKH
      who developed focal seizures and were treated in our department. Neurological
      exam was normal in 15 cases. When abnormal, it showed postictal obnubilation or
      diabetic polyneuropathy. Interictal EEG (obtained in 17 patients) showed focal or
      generalised slowing in 65% of cases, and ictal EEG (six patients) showed rapid
      spikes most often unilateral. CTs were normal in 77% of cases, and showed age
      compatible cortico-subcortical atrophy in the others. All patients were alert,
      with glucose values between 13.6 and 55 mmoles/l and osmolarity values increased
      in all cases to a mild or moderate extent (266-309.20 mosm/l). Three out of 22
      patients (14%) presented with motor epilepsy partialis continua. In 11/22 cases
      (50%), diabetes mellitus had not been diagnosed previously. Seizures associated
      with NKH were resistant to anticonvulsant treatment but responded well to insulin
      therapy and rehydration. They subsided completely in an average of 4 days, and
      only one patient had to be transiently transferred to ICU. We conclude on the
      importance of an early diagnosis of this condition to prevent malignant evolution
      of the epileptic syndrome into a state of hyperosmolarity and coma associated
      with a much higher mortality.

PMID- 15501690
TI  - [Research into the best conditions for the care and treatment of juvenile
      diseases].

PMID- 15501691
TI  - mTOR: a protein kinase switching between life and death.
AB  - The mammalian target of rapamycin (mTOR) is a central regulator of ribosome
      biogenesis, protein synthesis, cell growth and neurite plasticity. The mTOR
      kinase controls the translation machinery, in response to amino acids and growth
      factors, via activation of p70 ribosomal S6 kinase (p70S6K) and inhibition of eIF
      4E binding protein (4E-BP1). The mTOR protein belongs to the PI3K pathway
      activated by insulin, nutrients and growth factors. The PI3K pathway involves the
      Akt kinase, an upstream regulator of mTOR. Rapamycin is a potent
      immunosuppressant and investigational anticancer drug, which inhibits mTOR,
      blocking protein synthesis and arresting the cell cycle in G1 phase. A wide body
      of evidence supports the role of mTOR in cell signaling related to cell growth
      and proliferation. Nevertheless, our recent findings have revealed that mTOR may
      be also involved in a signaling pathway activated by microtubule-damaging drugs,
      including taxol and nocodazole. It is known that agents affecting the integrity
      of microtubules activate apoptotic program by inducing phosphorylation and
      inactivation of the antiapoptotic Bcl-2 protein in G2-M phase. We have some
      evidence that mTOR is involved in the enzymatic cascade that, starting from
      damaged microtubules, induces downstream phosphorylation of the Bcl-2 protein. We
      also found that the level of activity of Akt can regulate Bcl-2 phosphorylation,
      through the mTOR kinase. Since mTOR activation by survival signals occurs in G1
      phase and damaged microtubules activate proapoptotic signals in G2-M phase, we
      suggest that mTOR might mediate these two different pathways in two different
      phases of the cell cycle.

PMID- 15501692
TI  - Methadone--metabolism, pharmacokinetics and interactions.
AB  - The pharmacokinetics of methadone varies greatly from person to person; so, after
      the administration of the same dose, considerably different concentrations are
      obtained in different subjects, and the pharmacological effect may be too small
      in some patients, too strong and prolonged in others. Methadone is mostly
      metabolised in the liver; the main step consists in the N-demethylation by CYP3A4
      to EDDP (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine), an inactive
      metabolite. The activity of CYP3A4 varies considerably among individuals, and
      such variability is the responsible for the large differences in methadone
      bioavailability. CYP2D6 and probably CYP1A2 are also involved in methadone
      metabolism. During maintenance treatment with methadone, treatment with other
      drugs may be necessary due to the frequent comorbidity of drug addicts:
      psychotropic drugs, antibiotics, anticonvulsants and antiretroviral drugs, which
      can cause pharmacokinetic interactions. In particular, antiretrovirals, which are
      CYP3A4 inducers, can decrease the levels of methadone, so causing withdrawal
      symptoms. Buprenorphine, too, is metabolised by CYP3A4, and may undergo the same
      interactions as methadone. Since it is impossible to foresee the time-lapse from
      the administration of another drug to the appearing of withdrawal symptoms, nor
      how much the daily dose of methadone should be increased in order to prevent
      them, patients taking combined drug treatments must be carefully monitored. The
      so far known pharmacokinetic drug-drug interactions of methadone do not have life
      threatening consequences for the patients, but they usually cause a decrease of
      the concentrations and of the effects of the drug, which in turn can cause
      symptoms of withdrawal and increase the risk of relapse into heroin abuse.

PMID- 15501693
TI  - High glucose concentration augments angiotensin II mediated contraction via AT1
      receptors in rat thoracic aorta.
AB  - Elevated glucose concentration is implicated to play major role in development of
      diabetic associated vascular complications. It was previously reported that
      angiotensin II (Ang II) induced contractile response is enhanced in thoracic
      aorta of diabetic rats. In the present study, the effect of high glucose (HG, 25
      mM) exposure for 2h on Ang II cumulative concentration response curves recorded
      isometrically was studied in thoracic aortic rings isolated from male Sprague
      Dawley rats pretreated with streptozotocin (STZ, 65 mg kg(-1) i.p.) or vehicle at
      8 weeks prior to the study. Ang II induced contraction via AT1 receptor was
      significantly enhanced (by 60 +/- 2 %) in HG exposed thoracic aortic rings
      isolated from vehicle treated but not STZ treated rats. However, there was no
      change in the pD2 of Ang II while potassium chloride (KCl) induced contraction
      was unaltered. Ang II induced contractile response was blocked by valsartan (100
      microM, selective AT1 receptor antagonist) but not PD 123,319 (100 microM,
      selective and potent AT2 receptor antagonist). Exposure of aortic rings from
      control rats to 25 mM mannitol or sucrose for 2 h did not have any effect on the
      Ang II induced contraction. Tempol (100 microM, a cell permeable superoxide
      dismutase mimetic) partially reduced the augmented Ang II response in HG exposed
      aortic rings, while it did not affect the Ang II responses in normal glucose (NG
      5.5 mM) exposed aortic rings isolated from control rats. [3H] Ang II binding at
      AT1 receptors was unaltered in vascular smooth muscle membranes prepared from
      thoracic aorta exposed to HG for 2 h compared to NG exposed aortic rings. From
      our results, we conclude that high glucose concentration augments Ang II mediated
      contraction via AT1 receptors and reactive oxygen species partly contribute to
      this augmented contraction.

PMID- 15501694
TI  - Chronic treatment of haloperidol causes vasoconstriction on basilar arteries of
      rats, dose dependently.
AB  - Haloperidol is a widely used antipsychotic drug, which exerts its effects via
      antagonizing the dopaminergic D2 receptors. Also it affects a number of receptors
      on vascular bed and other tissues. The impact of haloperidol on vascular bed
      seems still debatable and not clear. In the present study, haloperidol was given
      to adult rats in 0.5, 1, 2.5 and 5 mg kg(-1) doses, once a day, intraperitoneally
      in 1 ml volumes, for 9 weeks. After decapitation under Pentothal anesthesia,
      brains and basilar arteries were dissected out at midpontine level immediately.
      Conventional histopathology and morphometric analysis were carried out on the
      dissected artery branches. Medial and adventitial layers, endothelial cells and
      internal elastic membranes were observed as normal in the control group. It was
      determined clearly that the lumen of basilar artery in the control group was
      larger than in the other groups and also it was observed that is more regular the
      lumen contours of basilar artery in control group compared with other groups.
      Finally, wall thickness of basilar artery in all experimental groups decreased
      significantly due to the vasoconstriction. Regarding the total, lumen and wall
      volumes, 1 mg kg(-1) haloperidol induces vasoconstriction more than the other
      groups.

PMID- 15501695
TI  - Responses to bradykinin are mediated by NO-independent mechanisms in the rat
      hindlimb vascular bed.
AB  - The vasodilator response to bradykinin (BK) appears to be mediated by a number of
      different endothelium-derived relaxing factors (EDRFs). The EDRFs mediating the
      response depend on the species and vascular bed studied. The mechanism by which
      BK dilates the hindlimb vascular bed was investigated in the anesthetized rat. BK
      produced dose-dependent increases hindlimb blood flow. The NOS antagonist L-NAME
      had little effect on the magnitude of the increase in flow when baseline
      hemodynamic parameters were corrected by an NO donor infusion. However, the
      duration of the response was slightly shortened by L-NAME. Charybdotoxin (Chtx)
      and apamin nearly abolished the L-NAME resistant component of the hindlimb
      vasodilator response to BK, but did not affect the hindlimb vasodilator response
      to the sodium nitroprusside (SNP). The cyclooxygenase inhibitor meclofenamate and
      the K+-ATP channel blocker U37883A, in the presence of L-NAME, did not alter the
      vasodilator response to BK. These results suggest that a significant portion of
      the hindlimb vasodilator response to BK is mediated by the activation of KCa
      channels, and independent of NO synthesis, cyclooxygenase products, and
      activation of K+-ATP channels. The present data suggest that the mechanisms
      mediating the vasodilator response to BK in the hindlimb vascular bed of the rat
      are complex, consisting of a Chtx and apamin sensitive, L-NAME resistant phase
      and a minor phase mediated by NO. In contrast, NO accounts for about half of the
      hindlimb vasodilator response to acetylcholine (ACh), with the other half of the
      response mediated by a Chtx and apamin sensitive mechanism. Additionally, the
      present results demonstrate that the NO donor infusion technique is able to
      compensate for the loss of basal NO production following inhibition of NOS, and
      to restore hemodynamic parameters to pre-L-NAME levels, making it a useful
      technique for the investigation of the role of NO in mediating vascular
      responses.

PMID- 15501696
TI  - Oxidized low-density lipoproteins accumulate in rat lung after experimental lung
      edema induced by alpha- naphthylthiourea (ANTU).
AB  - Oxidation of the low-density lipoprotein (LDL) results in the production of
      modified LDLs. Oxidation of LDL cholesterol plays a role on the pathogenesis of
      endothelial dysfunction. This study was designed to investigate the possible
      participation of the oxidative modification of low density lipoprotein in the
      lung edema induced by alpha-naphthylthiourea (ANTU), which is a well-known
      noxious chemical agent on the lung endothelium. When ANTU injected
      intraperitoneally into rats (15 mg kg(-1)), it produced lung edema as indicated
      by an increase in lung weight/body weight (LW/BW) ratio and pleural effusion (PE)
      reaching a maximum within 4 h. A significant lung edema was observed 4 h after
      intraperitoneally injection of alpha-naphthylthiourea when compared with olive
      oil-injected control rats. On microscopic examination of alpha-naphthylthiourea
      treated rats were shown to have severe lung injury, while no change was observed
      in olive oil-treated control rats. While there were no staining in control lungs,
      positive oxidized low-density lipoproteins immune-fluorescent staining were
      observed in lung edema group. Our study showed that oxidized low-density
      lipoprotein (oxLDL) accumulated in ANTU-induced lung damage. This is the first
      study in which accumulation of oxLDL molecules in the intact lung tissue were
      shown by fluorescent immune-staining method in experimental lung edema. The
      potential role of oxLDL in this pathology are still under investigation.

PMID- 15501697
TI  - Acute hyperglycemia attenuates nerve conduction velocity and nerve blood flow in
      male Sprague-Dawley rats: reversal by adenosine.
AB  - Hyperglycemia is implicated to play a major role in development of diabetic
      neuropathy. Since most of the diabetics are hyperglycemic much before they
      develop full-blown diabetes, we felt, it would be very important to know the
      effects of acute hyperglycemia on nerve function so that early pathophysiological
      events could be understood and appropriate therapeutic intervention can be made.
      Moreover, effect of acute hyperglycemia on motor nerve conduction velocity (MNCV)
      and nerve blood flow (NBF) is not known. Hence, we studied the effects of acute
      hyperglycemia on sciatic MNCV and sciatic NBF in healthy male Sprague-Dawley (SD)
      rats. Three different animal models of acute hyperglycemia (50% glucose (3 g kg(
      1), i.v. (intra-venous) or i.p. (intra-peritoneally)) or 24 h post-streptozotocin
      (STZ) injected rats were used. Acute hyperglycemia but not mannitol or sucrose
      significantly attenuated MNCV and NBF. Adenosine (10 mg kg(-1), i.p.) prevented
      the acute hyperglycemia-induced attenuation of MNCV and NBF in all the three rat
      models of acute hyperglycemia. Adenosine effects were blocked by theophylline (50
      mg kg(-1), i.p.) suggesting the role of adenosinergic receptor mediated
      mechanisms in acute hyperglycemia-induced neuropathy. Acute glucose
      administration in 8 weeks, STZ diabetic rats did not further affect MNCV or NBF.
      Adenosine (10 mg kg(-1), i.p.) did not produce any adverse effects on the blood
      pressure and heart rate. From the results, we conclude that acute hyperglycemia
      attenuates MNCV and NBF via an adenosinergic receptor-dependent mechanism.

PMID- 15501698
TI  - Oral anticoagulant therapy in Italy: prescribing prevalence and clinical reasons.
AB  - BACKGROUND: Oral anticoagulants (OAs) are recommended for many clinical problems
      and their use requires organised and knowledgeable medical support. Up to our
      knowledge, there is no data about both the reasons of treatment among OAs' users
      and the number of patients prescribed with OAs in Italy. OBJECTIVES: To describe
      the OA use, and the reasons of prescribing among Italian General Practitioners.
      METHODS: We used the Health Search Database owned by the Italian College of
      General Practitioners to identify the clinical records of patients > or =20 years
      who had at least one prescription of OAs during the year 2002. RESULTS: Among a
      study population of 448,495 patients, 3,649 subjects (0.81%) had received at
      least one OAs prescription. Applying such a proportion to the overall Italian
      population, on the basis of data from Italian Office for National Statistics
      (ISTAT), we estimated that 376,882 patients would have used OAs during the year
      2002 in Italy. The most frequent clinical problem related to the use of OAs was
      atrial fibrillation (45.6%), followed by cardiac valve disease (14.6%), deep vein
      thrombosis (12.2%) and peripheral artery embolism (7.7%). CONCLUSIONS:
      Approximately 370,000 patients are prescribed with OAs in Italy and for more than
      50% of them life-long therapy is recommended. Atrial fibrillation is the most
      frequent reason for prescription.

PMID- 15501699
TI  - Interaction between saquinavir and antimycotic drugs on C. albicans and C.
      neoformans strains.
AB  - Candidiasis and cryptococcosis are the most common fungal diseases among patients
      suffering from HIV infection. In the present work we assess whether the combined
      therapies, proteinase inhibitors and antimycotic drugs, could modify the
      therapeutic effect of antimycotics. An in vitro study to evaluate the antifungal
      effect of saquinavir and antimycotic drugs combination on yeast growth was
      performed. Strains of C. albicans and C. neoformans from HIV-seropositive
      patients were used. Susceptibility tests of yeasts to amphotericin B, 5
      fluorocytosine, miconazole and fluconazole, singly and in combination with
      saquinavir, were performed in two different media. In the combinations the
      antimycotic agents and saquinavir were tested at sub-inhibitory concentrations:
      0.1-10 microg ml(-1) and 12.50 microg ml(-1), respectively. The fractionary
      inhibitory concentration (FIC) index was also calculated. The results show that
      the interaction between saquinavir and all the antimycotic drugs never resulted
      in antagonism. Fluconazole acts in more synergistic way, no matter which medium
      is used. The combined therapy miconazole/saquinavir results in synergism,
      especially in Sabouraud. The total absence of antagonism and the presence of
      synergism suggest that a combined therapy could be proposed in the treatment of
      HIV-seropositive patients to reduce side effects, thanks to the use of lower
      doses of antimycotic drugs.

PMID- 15501700
TI  - Tachykinin NK3-receptor deficiency does not inhibit pulmonary eosinophilia in
      allergic mice.
AB  - Tachykinins are important in the development of pulmonary inflammation in mice
      but the tachykinin receptor subtype mediating this response has not been defined.
      To elucidate the role of tachykinin NK3-receptors on allergen-induced pulmonary
      inflammation, studies were performed on ovalbumin (OVA) sensitized and challenged
      mice with genetic disruption of the tachykinin NK3-receptor (NK3-/-). Aerosol OVA
      (0.5%) challenge produced eosinophil influx into the bronchoalveolar lavage fluid
      and lung tissue, goblet cell hyperplasia and damage to the airway epithelium of
      both NK3-/- mice and in wild type control mice (NK3+/+). There was no difference
      in the magnitude of these allergic inflammatory pulmonary responses between NK3-/
      and NK3+/+ mice. These results find no role for tachykinin NK3-receptors on the
      pulmonary eosinophilia and lung damage after antigen challenge in mice.

PMID- 15501701
TI  - Vasopressin excitatory action on smooth muscle from human renal calyx and pelvis.
AB  - The motor response to vasopressin, a neuropeptide promoting the reabsorption of
      water, was isometrically investigated in vitro in human renal calyces and pelvis
      in relation to possible modulation of urinary flow by these tubular structures.
      Kidneys were obtained from nine male patients who underwent nephrectomy for
      either renal or ureteral cancer. Minor calyces and pelvis were carefully removed.
      Strips (10 mm x 3 mm) were cut from infundibular region of minor calyces and from
      renal pelvis and placed in 10 ml organ bath for isometric tension recordings.
      Calyceal and pelvic smooth muscle strips exhibited spontaneous phasic
      contractions which occurred with regular frequency and amplitude. Vasopressin
      induced a dose-dependent [10(-10) to 10(-6) M] enhancement of basal tone (P
      <0.01) and a decrease of spontaneous contractions on isolated strips from minor
      calyces and pelvis. The effect of vasopressin was inhibited by prior
      administration of D(CH2)5Tyr(Me)2-Arg8-Vasopressin antagonist [10(-7) M]. The
      excitatory response to vasopressin was Tetrodotoxin [TTX]-resistant and was not
      affected by pre-treatment with phentolamine [10(-5) M], atropine [10(-5) M], and
      hexamethonium [10(-5) M]. After incubation of the specimens in Ca2+-free medium
      containing EGTA [0.5 mM] or after treatment with nifedipine [10(-5) M], both
      spontaneous and vasopressin-induced contractions [10(-10) to 10(-6) M] were
      completely inhibited in all specimens. Our results can be interpreted to imply
      that the tonic contractions induced by vasopressin facilitate the reabsorption of
      water by increasing the hydraulic resistance of the tubular structures below
      collecting ducts.

PMID- 15501702
TI  - Effect of trimetazidine on renal ischemia/reperfusion 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 trimetazidine, in I/R induced renal
      failure in rats. The protective effect of trimetazidine (Tmz) 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. Trimetazidine (3 mg kg(
      1), i.p.) was administered 30 min prior to ischemia and repeated 12 h after the
      first dose. At the end of the reperfusion period, rats were sacrificed.
      Thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH)
      levels, glutathione reductase (GR) catalase (CAT), and superoxide dismutase (SOD)
      activities were determined in renal tissue. Serum creatinine and blood urea
      nitrogen (BUN) 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 trimetazidine 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 trimetazidine exert renoprotective effects probably by
      the radical scavenging and antioxidant activities.

PMID- 15501703
TI  - Adverse drug events in two emergency departments in Naples, Italy: an
      observational study.
AB  - The aims of this study, conducted in the emergency departments of two hospitals
      of Naples (Italy), which differ in type of catchment area and in the number of
      daily visits, were to determine: (1) the percent of emergency department visits
      due to adverse drug events (ADEs); (2) the percent of visits requiring
      hospitalisation due to acute ADEs; (3) the drugs implicated in ADEs; and (4) the
      types of ADEs and their frequency. We studied all emergency department visits at
      the A. Cardarelli and Incurabili hospitals between 8.00 a.m. and 8.00 p.m.
      (prospectively), and between 8.00 p.m. and 8.00 a.m. (retrospectively) for two 10
      day periods. When possible, a form was completed for each subject. Patients were
      asked if they had taken a drug (name, dosage and reason for its use) in the
      previous 2 weeks. Of the 2442 emergency visits considered, 34 (1.3%) were drug
      related. Of the 480 patients who were subsequently hospitalised 17 (3.6%) had an
      ADE. The number increased to 34 (8.9%) in the 379 patients who took drugs in the
      2 previous weeks. Non-steroidal anti-inflammatory drugs accounted for 26.5% of
      cases, antibiotics 23.6%, and antihypertensive agents 17.7%. The most frequent
      ADEs were gastrointestinal diseases (diarrhea, vomiting and haemorrhagic
      gastritis) and cutaneous rash (erythema, dermatitis). This study shows that ADEs
      account for a large percent of hospital admissions and confirms that drug-induced
      disorders is a notable public health problem.

PMID- 15501704
TI  - Effect of supplementation of calcium and vitamin D on bone mineral density and
      bone mineral content in peri- and post-menopause women; a double-blind,
      randomized, controlled trial.
AB  - BACKGROUND: Osteoporosis is a serious global health problem for the future, that
      is why improving diagnostic methods and prevention of this disease could be
      helpful. OBJECTIVES: To assess the effects of calcium supplementations combined
      with Vitamin D on bone mineral density (BMD) and bone mineral content (BMC) in a
      representative sample of peri- and post-menopausal women in a double-blind, a
      randomized, controlled trial was untaken. DESIGN: A total of 120 women aged over
      45 were included in a randomised placebo-controlled, double-blind trial on the
      effect of a daily dietary supplementation of calcium and Vitamin D on bone
      mineral density and bone mineral content; over a 30-month period. METHODS:
      Dietary intake assessment; dual-energy X-ray absorptiometry to measure total body
      and segmental bone mineral density and bone mineral content at beginning of the
      study and every 15 months were undertaken. RESULTS: There was no significant
      change in dietary calcium or Vitamin D intakes in either of the treatment groups
      during the 30-month intervention period. The change in total BMD in the calcium
      group was significantly different from that in the placebo group (P <0.005). The
      placebo group lost a total BMD at a rate of about 0.4% per year. There was an
      inverse correlation between BMD and age. CONCLUSIONS: The effect of calcium and
      Vitamin D supplementation on bone mineral density of calcium has been
      demonstrated in this group of young adult women. Our results showed the positive
      effect of calcium and Vitamin D supplementation in women both peri- and post
      menopausal status; for this reason a supplementation of calcium and Vitamin D
      should be recommended as a strategic option in helping to prevent early
      postmenopausal bone loss.

PMID- 15501705
TI  - Synthesis of tin nanorods via a sonochemical method combined with a polyol
      process.
AB  - Metallic tin nanorods were synthesized by a sonochemical method employing the
      polyol process. In the reaction a solution of SnCl2 in ethylene glycol was
      exposed to high-intense ultrasound irradiation. The phase and elemental
      compositions, and thermal properties of the as-synthesized samples were
      characterized by XRD, EDX, SAED, XPS, DSC, TGA, and BET measurements. The
      morphologies of the products were further characterized with SEM, TEM, and HRTEM.
      The results show that crystallized metallic tin nanorods in diameters of 50-100
      nm and in lengths of up to 3 microm were synthesized. The nanorods are
      encapsulated in a thin layer containing Ti and carbon compounds. On the basis of
      the obtained data, a possible mechanism of the formation of tin nanorods was
      proposed.

PMID- 15501706
TI  - Structural analysis of sonochemically prepared Au/Pd nanoparticles dispersed in
      porous silica matrix.
AB  - Bimetallic Au/Pd nanoparticles supported on a silica matrix were prepared by an
      ultrasonic technique. The samples heat-treated at 100, 200, 300 and 400 degrees C
      were examined with techniques of XRD (X-ray diffraction), TEM and XAS (X-ray
      absorption spectrometry) for studying correlation between their structure and the
      catalytic activity of hydrogenation of cyclohexene. Even after the heat treatment
      at 400 degrees C, the particles were smaller than 20 nm and well dispersed in the
      matrix without agglomeration nor sintering. Results of the XRD, TEM and XAS
      indicated that the as-prepared particles have a core/shell structure of Au/Pd and
      transform into a random alloy at 300 degrees C. The catalysis seemed to be
      deactivated by alloying.

PMID- 15501708
TI  - Kinetics of ultrasonic degradation of phenol in the presence of TiO2 particles.
AB  - The degradation of phenol by ultrasonic irradiation in the presence of TiO2 was
      investigated in complete darkness. The effects of amount of TiO2 and the
      combination of TiO2 addition with gas (air or oxygen) supply on the degradation
      kinetics of phenol and the formation of the reaction products were examined. The
      degradation rate of phenol increased with the amount of TiO2. As the dissolved
      oxygen concentration increased by supplying oxygen, the degradation rate of
      phenol also increased. A kinetic model for the disappearance of phenol was
      proposed. The model takes into account the OH radical formation by direct water
      degradation, indirect degradation by oxygen atom and indirect degradation by TiO2
      catalysis. The calculated results explained well the fact that a higher amount of
      TiO2 and dissolved oxygen concentration gave faster disappearance rate.

PMID- 15501707
TI  - Sonochemical degradation of azo dyes in aqueous solution: a new heterogeneous
      kinetics model taking into account the local concentration of OH radicals and azo
      dyes.
AB  - The sonochemical decolorization and decomposition of azo dyes, such as C. I.
      Reactive Red 22 and methyl orange, were performed from the viewpoints of
      wastewater treatment and to determine the reaction kinetics. A low concentration
      of the azo dye solution was irradiated with a 200 kHz and 1.25 W/cm2 ultrasound
      in a homogeneous aqueous solution. The azo dye solutions were readily decolorized
      by the irradiation. The sonochemical decolorization was also depressed by the
      addition of the t-butyl alcohol radical scavenger. These results indicated that
      azo dye molecules were mainly decomposed by OH radicals formed from the water
      sonolysis. In this paper, we propose a new kinetics model taking into account the
      heterogeneous reaction kinetics similar to a Langmuir-Hinshelwood mechanism or an
      Eley-Rideal mechanism. The proposed kinetics model is based on the local reaction
      site at the interface region of the cavitation bubbles, where azo dye molecules
      are quickly decomposed because an extremely high concentration of OH radicals
      exists in this region. To confirm the proposed kinetics model, the effects of the
      initial concentration of azo dyes, irradiated atmosphere and pH on the
      decomposition rates were investigated. The obtained results were in good
      agreement with the proposed kinetics model.

PMID- 15501709
TI  - Effect of sonication on the photo-catalytic mineralization of some chlorinated
      organic compounds.
AB  - Effects of the irradiation of ultrasound (US) on the photo-catalytic
      mineralization of some chlorinated organic compounds such as dichloroethane, tri-
      and tetrachloroethylenes, chloroacetic acids and chloromethanes were examined in
      oxygen saturated aqueous solutions suspended titanium dioxide (P25) particles.
      The yields of the sonochemical mineralization for these compounds were found to
      be extremely low compared to the photo-catalysis. However, the pre-sonication, US
      irradiation on the sample solution before the photo-irradiation, enhanced
      significantly the following photo-catalytic degradation to the complete
      oxidation. The effect was investigated in detail and it was found that the effect
      was mainly owing to the increase in the capability of the catalysis of which
      particles were sparsely dispersed by the sonication. The other contribution of
      the pre-sonication effect was found to be "pre-sonolysis", the initial formation
      of some intermediated products sonochemically, which are oxidizable more rapidly
      further to carbon dioxide than the original compound by the following photo
      catalytic reactions. The pre-sonolysis effect was observed remarkably for
      trichloroacetic acid and tetrachloromethane, both of which are known to be hardly
      reactive to the photo-catalytic degradation. The photo-catalytic degradation with
      simultaneous sonication were also carried out for these compounds. The synergetic
      effect in the mineralization was observed both for carbontetrachloride and for
      trichloroacetic acid, the higher carbon dioxide yield being obtained in the
      simultaneous reaction than the sum of the yields in the photo-catalysis and the
      sonolysis each alone, while no significant synergetic effect was observed in the
      mineralization of other compounds.

PMID- 15501710
TI  - Regeneration of granular activated carbon using ultrasound.
AB  - To evaluate the feasibility of ultrasonic regeneration of granular activated
      carbon (GAC), desorption of trichloroethylene (TCE) from GAC by ultrasound was
      investigated at 20 kHz. About 64% of TCE was desorbed from 5 g of GAC loaded with
      6.5 mg TCE for 1 h in ultrasonic field and TCE desorbed to liquid phase were
      rapidly degraded by ultrasound. 34-43% of stoichiometrically calculated chloride,
      final degradation product of TCE, was observed in liquid phase during ultrasonic
      treatment. However, there was desorption limitation at 20 kHz ultrasound. Despite
      of prolonged ultrasonic irradiation, desorption efficiency of TCE did not exceed
      critical value. And also, the higher percentage of TCE was desorbed when a sample
      of 2 mg TCE/4 g GAC was treated ultrasonically than that of 2 mg TCE/g GAC under
      the same experimental conditions. These results indicate that desorption of TCE
      by 20 kHz ultrasound occurred mainly at a nearby surface of GAC. In conclusion,
      the ultrasonic regeneration showed a possibility as an alternative to chemical
      and thermal regenerations of GAC.

PMID- 15501711
TI  - A combination of ultrasound and oxidative enzyme: sono-enzyme degradation of
      phenols in a mixture.
AB  - Sono-degradation and sono-enzyme degradation of phenols were performed on the
      mixtures of double compounds (phenol, p-chlorophenol; phenol, p-cresol; phenol, p
      nitrophenol; and p-chlorophenol, p-cresol) in aqueous medium. Sono-degradation of
      phenol and its substituted compounds individually behaved approximately the same,
      but in the case of mixture behaved differently. Sono-degradation of substituted
      phenols was easier than phenol in a mixture, but there was an exception in the
      combination of phenol and p-nitrophenol that the degradation of phenol was faster
      than substituted compound. This behavior was the same in sono-enzyme degradation,
      but with higher degradation rate. Between these mixtures, the combination of
      phenol and p-cresol presented a significant different behavior in case of single
      and double compounds solutions. In this system, the sono-degradation of phenol in
      mixture was more difficult than phenol alone but, the sono-degradation of p
      cresol in mixture was easier in comparison with p-cresol alone. In sono-enzyme
      degradation, p-cresol as a more reactive compound facilitated the remove of
      phenol in mixture in compare of the individual case.

PMID- 15501712
TI  - Application of ultrasonic irradiation to the sol-gel synthesis of silver vanadium
      oxides.
AB  - An ultrasonic irradiation method was applied to the sol-gel synthesis of silver
      vanadium oxides (SVO). Transmission electron microscope (TEM), X-ray diffraction
      (XRD), thermogravimetry (TG) and differential thermal analysis (DTA) were
      conducted to research the ultrasonically accelerated reaction between V2O5 gel
      and Ag2O powder. Galvanostatic discharge experiments showed that the as prepared
      cathode active material of Ag2V4O11 and Ag(1.2)V3O8 have better electrochemical
      properties than those synthesized by conventional solid state method.

PMID- 15501714
TI  - Bioleaching with ultrasound.
AB  - Application of bioleaching of metals in a large-scale operation is reviewed
      briefly. Continued technical innovation is vital for the wider utilisation of
      this extraction process within the mineral industries. Therefore, the use of
      power ultrasound in combination with bioleaching (referred to as sonobioleaching)
      has been studied and is shown to be beneficial in the recovery of nickel from
      lean grade ores. The role of ultrasound in improving the benefits and lowering
      the drawbacks of bioleaching to an acceptable level are described. A possible
      mechanism for improving and intensifying this process is hypothesised.

PMID- 15501713
TI  - Application of ultrasonic technique for extracting chlorogenic acid from Eucommia
      ulmodies Oliv. (E. ulmodies).
AB  - An ultrasonic method for the extraction of chlorogenic acid from fresh leaves of
      Eucommia ulmodies Oliv. was investigated and optimized. The influence of four
      extraction variables on extraction efficiency of chlorogenic acid was
      investigated. The optimum extraction conditions found were: 70% aqueous methanol;
      solvent: sample ratio=20:1 (v/w); extraction time 3 x 30 min. The recovery of
      chlorogenic acid was studied (HPLC) and the reproducibility of the extraction
      method was determined. The optimized ultrasonic extraction conditions were
      applied to extract chlorogenic acid from fresh leaves, fresh bark and dried bark
      of E. ulmodies and four traditional Chinese medicines. The application of
      sonication method was shown to be highly efficient in the extraction of
      chlorogenic acid from E. ulmodies and other Chinese medicines compared with
      classical methods.

PMID- 15501715
TI  - CuO based catalysts on modified acidic silica supports tested in the de-NOx
      reduction.
AB  - A series of dispersed CuO catalysts supported on modified silica supports with
      Al2O3 (SA), TiO2 (ST), and ZrO2 (SZ) were prepared optimising the adsorption
      method of copper deposition assisted by ultrasound treatment, already reported in
      a previous paper (S. Bennici, A. Gervasini, V. Ragaini, Ultrason. Sonochem. 10
      (2003) 61). The obtained catalysts were characterized in their bulk (atomic
      absorption, X-ray diffraction, temperature programmed reduction) and surface (N2
      adsorption, X-ray photoelectron spectroscopy, scanning electron microscopy)
      properties. The morphology of the finished materials was not deeply modified
      compared with that of the relevant supports. The employed complemented techniques
      evidenced a well dispersed CuO phase with a copper-support interaction on the
      most acidic supports (SA and SZ). The catalyst performances were studied in the
      reaction of selective catalytic reduction of NOx with ethene in oxidizing
      atmosphere in a flow apparatus under variable times (0.360-0.072 s) and
      temperatures (200-450 degrees C). The catalysts prepared on the most acidic
      supports (SA and SZ) were the most active and selective towards N2 formation.
      They showed a particular interesting activity in the reaction of NO2 reduction
      besides that of NO reduction.

PMID- 15501716
TI  - Enhancement of sonochemical degradation of phenol using hydrogen atom scavengers.
AB  - Sonochemical degradation of phenol was found to be enhanced in the presence of
      the volatile hydrogen atom scavengers CCl4 and perfluorohexane. The non-volatile
      hydrogen atom scavenger iodate did not enhance phenol degradation. The first
      order rate constant for aqueous phenol degradation in separate experiments using
      different sonochemical probes increased in the presence of 150 microM CCl4 from
      0.014 to 0.031 min(-1) (probe 1) and from 0.022 to 0.061 min(-1) (probe 2). In
      the presence of <1.5 microM C6H14, the first order rate constant increased from
      0.014 to 0.032 min(-1) (probe 1). Hydroquinone was the major observed reaction
      intermediate both in the presence and absence of hydrogen atom scavengers.
      Hydroquinone yields were substantially higher in the presence of hydrogen atom
      scavengers, suggesting that hydroxyl radical pathways for phenol degradation were
      enhanced by the hydrogen atom scavengers. These additives may be useful in
      improving pollutant degradation efficiency or improving synthetic processes that
      rely on hydroxyl radical as a key intermediate.

PMID- 15501717
TI  - Ultrasound-assisted hydrogenation of cinnamaldehyde.
AB  - The hydrogenation, employing hydrogen gas, of cinnamaldehyde was performed using
      Pd-black and Raney Ni catalysts at 298+/-3 K in a water-cooled (jacketed)
      reaction vessel. Sampling at pre-determined time intervals and GC/MS analysis
      yielded time-dependent product state distribution information. A kinetic modeling
      of the data revealed that cinnamaldehyde was both hydrogenated directly to the
      final product benzenepropanol, as well as a fraction being converted to the
      intermediate benzenepropanal, where the latter was subsequently hydrogenated to
      benzenepropanol. Comparing the ultrasound-assisted and blank (stirred)
      experiments revealed that a higher maximum relative concentration of the
      intermediate benzenepropanal was formed in the ultrasound experiments compared to
      the stirred experiment. The activity of the ultrasound experiments compared to
      blank were 9-fold and 20-fold greater for the Pd-black and Raney Ni catalysts,
      respectively. Finally, an application of the Bell-Evans-Polanyi principle to
      yield an estimate of the ratio of rate coefficients for benzenepropanal and
      benzenepropanol formation was performed by considering chemical group energy
      differences and surface adsorption energy differences in the first mechanistic
      step of hydrogenation.

PMID- 15501718
TI  - Quality: an old solution to new discovery dilemmas?

PMID- 15501719
TI  - Zebularine: a candidate for epigenetic cancer therapy.
AB  - For many years, the search for cancer therapy targets focused on the genetic
      changes associated with the transformation of normal cells into malignant cells.
      However, it is now clear that disruptions in epigenetic mechanisms--modifications
      of DNA or histones that heritably alter gene expression without mutating DNA--are
      important in cancer. Zebularine is a stable DNA cytosine methylation inhibitor
      that is currently in development as an epigenetic therapy for cancer.

PMID- 15501720
TI  - Stapled peptide induces cancer cell death.
AB  - Hydrocarbon stapling could enable peptides from the key domains of natural
      proteins to be used therapeutically. Using the technique on a peptide involved in
      apoptosis, researchers have succeeded in destroying cancer cells in a mouse model
      of leukaemia.

PMID- 15501721
TI  - Sulforaphane halts breast cancer cell growth.
AB  - Sulforaphane is a chemical found in cruciferous vegetables such as broccoli,
      sprouts and kale. This compound is a potent inducer of protective enzymes that
      provide defense against cancer-causing chemicals. Researchers have discovered
      that sulforaphane can halt human breast cancer cells in their tracks and have
      identified a new mechanism of action for the compound.

PMID- 15501722
TI  - Hans Kupper discusses science and venture capital.
AB  - Hans Kupper has over 30 years of experience in the biotechnology industry in
      areas from research to R&D management, technology assessment and business
      acquisitions. He received his PhD in 1974 from the University of Heidelberg.
      After additional academic research at the Massachusetts Institute of Technology
      in the USA and at the University of Heidelberg, Germany, he joined Biogen in
      1980. Here, he held various R&D positions, the last of which was Assistant
      Research Director. In 1985, he joined Behringwerke AG, Marburg, to build up and
      head the company's Molecular Biology Department and thereafter became Head of R&D
      of the Immunology/Oncology Business Unit. In 1999 he joined Global Life Science
      Ventures at their Munich office. Dr Kupper is the author of numerous publications
      and patents/applications and has also served as a consultant to the
      Pharmaceutical Industry and the European Commission. He is a board member of
      several early stage companies in the life sciences.

PMID- 15501723
TI  - Gene expression analysis enriched.

PMID- 15501724
TI  - Enhancing transdermal drug transport with low-frequency ultrasound.

PMID- 15501725
TI  - Microarray applications: emerging technologies and perspectives.
AB  - Highlights of the EuroBiochips conference, which was held in Hamburg, Germany, on
      22-24 June 2004. Topics addressed at the meeting included the uses of padlock
      probes and nanomechanical cantilevers and microarray applications for patient
      profiling.

PMID- 15501726
TI  - Strategies for designing clinical trials for oligonucleotide therapeutics.
AB  - Recent Phase III clinical trials for oligonucleotide therapeutics have yielded
      disappointing results. There is growing evidence that trial designs that consider
      the specific mode of action of these compounds are of crucial importance for
      their clinical testing. Early trials for oligonucleotide therapeutics should
      consider additional endpoints for the definition of a biologically active dose
      rather than focusing on the traditional concept of maximal tolerated dose. In
      later phases, alternative clinical endpoints and enriching sensitive study
      populations through innovative trial designs could improve the efficiency of
      clinical trials for oligonucleotide therapeutics.

PMID- 15501727
TI  - Beyond classical meta-analysis: can inadequately reported studies be included?
AB  - Classical meta-analysis requires the same data from each clinical trial, thus
      data-reporting must be of a high-quality. Imputation methods are used to include
      studies that provide incomplete information on variability and the fixed and
      random effects of a drug. Regression models can be used to include studies other
      than randomized placebo-controlled studies. In the example outlined here, the use
      of non-randomized single-arm studies and studies against comparator treatments
      has little influence on the estimation of the treatment effect in comparison with
      placebo, an effect that is based on the randomized placebo-controlled studies.
      The inclusion of other studies serves to increase the precision of the effect of
      the treatment compared with baseline. Although multiple imputation techniques
      enable a larger number of studies to be included, which will typically increase
      the precision of the estimated effect, a careful sensitivity analysis is also
      required.

PMID- 15501728
TI  - Targeting JNK3 for the treatment of neurodegenerative disorders.
AB  - c-Jun N-terminal kinases (JNKs) have been recognized as important enzymes in
      cellular function. JNK3, which is predominantly found in CNS neurons, has been
      implicated in several neurodegenerative diseases, including Alzheimer's disease,
      Parkinson's disease and stroke. In particular, JNK3 has been found to have an
      upstream role in neuronal ischemic apoptosis. JNK3 is highly expressed and
      activated in postmortem brains of individuals that suffered from Alzheimer's
      disease. Furthermore, mice that are deficient in JNK3 are more resistant to 1
      methyl-4-phenyl-1,2,4,6-tetrahydropyridine (a neurotoxin that mimics the
      neuropathological characteristics of Parkinson's disease) than their wild-type
      littermates. Because of the involvement of JNK3 in neuronal diseases, the
      inhibition of this enzyme is an attractive therapeutic target.

PMID- 15501733
TI  - [A986S polymorphism of calcium-sensing receptor gene is not related to bone
      mineral density or bone size in premenopausal Chinese women].
AB  - OBJECTIVE: To investigate the association of a calcium-sensing receptor (CaSR)
      gene missense polymorphism, 986Ala/Ser (A986S), with bone mineral density (BMD)
      and bone size in healthy Chinese premenopausal women. METHODS: A total of 285
      healthy Chinese premenopausal women (20.0 to 41.9 years of age) of Han
      nationality in the urban area of Shanghai were recruited for this study. The BMD
      and bone size of the spine and hip were measured by dual-energy X-ray
      absorptiometry. All the subjects were genotyped at the CaSR A986S site in exon 7
      with polymerase chain reaction followed by restriction enzyme BsaHI digestion.
      The presence of the restriction fragment site was represented by alanine (A),
      while its absence by serine (S), rendering the genotypes AA, AS, and SS. RESULTS:
      The genotype AS was rare and SS absent in these Chinese women, and no significant
      differences in the BMD or bone size of either the spine or hip were found between
      the two genotypes. CONCLUSION: Given the important role of the CaSR in calcium
      metabolism, further studies with useful genetic markers may have better chances
      to define the association of the CaSR gene with bone phenotype variations.

PMID- 15501734
TI  - [Detection of HCV antibody in 12 280 inpatients admitted not for infectious
      diseases].
AB  - OBJECTIVE: To study the status of hepatitis C virus (HCV) infection in the
      inpatients scheduled for operations and blood transfusion, thereby to avoid
      potential nosocomial infection and possible medical disputes. METHODS: Enzyme
      linked immunosorbent assay (ELISA) was used to detect HCV antibody and HBsAg in
      the blood samples from 12 280 inpatients admitted in other medical departments
      than the department of infectious disease, who were scheduled for operations and
      blood transfusion. RESULTS: In the 12 280 blood samples, the positivity rate of
      HCV antibody was 1.03%, and those of both HBsAg and HCV was 0.17%. CONCLUSION:
      The positivity rate of HCV antibody is higher in these patients than in the
      healthy population, suggesting the necessity of HCV antibody detection in
      patients admitted not for infectious diseases before operation and blood
      transfusion.

PMID- 15501736
TI  - [Detection and sequence analysis of Sapporo-like virus in Guangzhou].
AB  - OBJECTIVE: To verify the presence of Sapporo-like virus (SLV) in children with
      diarrhea in Guangzhou. METHODS: Stool specimens were collected from children with
      diarrhea treated in the Department of Pediatrics of Nanfang Hospital in autumn
      and winter, 2003, and semi-nested reverse transcriptase-polymerase chain reaction
      (RT-PCR) was employed for SLV detection, the positive product of which was
      sequenced and analyzed in comparison with the SLV sequences documented in
      GenBank. RESULTS: Only one positive specimen (CH03354) was found out of the 169
      stool specimens collected. Sequence analysis of the capsid gene of this strain
      showed that it belonged to SLV GI-1 cluster. CONCLUSION: SLV exists in Guangzhou
      and different regions of China may have different genotypes of this virus.

PMID- 15501735
TI  - [Value of galvanic skin response in assessment of diabetic autonomic neuropathy].
AB  - OBJECTIVE: To explore a method for early detection of diabetic autonomic
      neuropathy (DAN) on the basis of analysis of galvanic skin response (GSR).
      METHODS: In 25 randomly selected diabetic inpatients (14 with clinical DAN
      symptoms), GSR signals were collected from the fingers of both hands based on
      Virtual Instrumental WorkBench-LabVIEW and compared with those acquired from
      normal subjects. RESULTS: The GSR indices of patients either with or without DAN
      were different from those of normal subjects, and even in the same patients, the
      changes of these indices after clinical treatment were also obvious. CONCLUSION:
      GSR detection and analysis can help understand the impairment of the autonomic
      system and facilitate DAN assessment.

PMID- 15501737
TI  - [Effects of neonatal calf serum on differentiation of human fetal neural stem
      cells in the hippocampus].
AB  - OBJECTIVE: To investigate the effects of neonatal calf serum on the
      differentiation of human neural stem cells in the hippocampus. METHODS: The
      effects of various concentrations of neonatal calf serum on the differentiation
      of human fetal neural stem cells in the hippocampus were observed in cell culture
      experiment and immunocytochemical staining. RESULTS: Neonatal calf serum
      efficiently induced the differentiation of human fetal neural stem cells into
      neurons and astrocytes, whose amount varied between serum-free cell culture and
      the culture with neonatal calf serum of different concentrations. As the
      concentration of neonatal calf serum increased, the differentiation of human
      fetal neural stem cells shifted toward astrocytes, while the differentiation into
      neurons was decreased. CONCLUSION: Neonatal calf serum causes alteration of the
      ratio between neurons and glial cells differentiated from human neural stem cells
      in the hippocampus.

PMID- 15501738
TI  - [18F-FDG positron emission tomography for mediastinal staging of lung cancer].
AB  - OBJECTIVE: To evaluate the diagnostic value of (18)F-FDG positron emission
      tomography (PET) in mediastinal staging of lung cancer. METHOD: A retrospective
      analysis of mediastinal staging was carried out in 41 cases of lung cancer by
      comparing the preoperative mediastinal FDG PET and CT findings with the
      pathological results. RESULTS: According to the pathological results, 18 patients
      had mediastinal metastasis, 17 of whom were correctly identified by FDG PET, and
      10 by CT. Of the other 23 patients without mediastinal metastasis pathologically,
      22 were correctly diagnosed by FDG PET and 20 by CT. The sensitivity and accuracy
      for diagnosis of regional mediastinal lymph node metastasis with FDG PET were
      94.4% and 95.1%, obviously higher than those of CT (55.6% and 73.2%, P<0.05).
      CONCLUSION: FDG PET is a better alternative for mediastinal staging of lung
      cancer, specially for identification of small lymph node metastasis escaping
      detection by CT, to provide important evidence for clinical staging and treatment
      planning of lung cancer.

PMID- 15501739
TI  - [Cantharidin regulates intracellular ATP in G1/S-phase renal tubule epithelial
      cells].
AB  - OBJECTIVE: To study the mechanism of cantharidin in protecting F-actin
      microfilaments from disruption by hypoxic damage by observing the effects of
      cantharidin on intracellular ATP metabolism in G(1)/S-phase renal tubule
      epithelial cells (RTECs). METHODS: G1-phase RTECs were divided into cantharidin
      treated group, exposed to sodium cyanide (CN) and cantharidin, hypoxic-group with
      CN exposure and non-treated control group. ATP levels were measured in the 3
      groups with high-performance liquid chromatography. RESULTS: The concentration of
      CN exposure for 1 h, ATP level in the RTECs with cantharidin treatment were
      significantly higher than that in both hypoxic and non-treated control groups
      (14.50+/-0.26 mmol/g protein, 4.25+/-0.11 mmol/g protein, 8.58+/-0.13 mmol/g
      protein, respectively, P<0.01). CONCLUSION: Cantharidin prevents the disruption
      of the actin cytoskeleton in hypoxic damage by preventing abnormal intracellular
      ATP metabolism.

PMID- 15501740
TI  - [Technical improvement of mechanical suture of bronchial stumps in
      pneumonectomy].
AB  - OBJECTIVE: To prevent or reduce such postoperative complications of pneumonectomy
      as bronchopleural fistula and promote the curative effect of the surgery by
      improving the technique for handling the bronchial stumps. METHODS: In 107
      patients, bronchial stapler was adopted for closure of the bronchial stump and
      pneumonectomy was subsequently performed on the side of the staples. A 1-0
      polyester suture was used to for suture in the shape of "U" deep in the
      mechanical suture on the bronchial stump. The postoperative complications were
      observed. RESULTS: The operations were performed easily and the bronchial stumps
      were short and sutured firmly. No fluid retention or granuloma occurred in the
      stumps after the operation, nor were the complications such as intractable cough
      and infection of thoracic cavity observed. No bronchopleural fistula was found in
      these patients. CONCLUSION: This new method is safe and effective for treatment
      of the bronchial stumps.

PMID- 15501741
TI  - [Value of magnesium sulfate and/or valium in preventing local anesthetic toxicity
      of sacral block].
AB  - OBJECTIVE: To study the effects of magnesium sulfate and/or valium in preventing
      local anesthetic toxicity induced by sacral block. METHODS: A total of 240 adult
      patients scheduled for sacral block were randomized equally into four groups
      matched for sex, age and body weight. Ten minutes before sacral block, the
      patients in group B received valium (0.1 mg/kg), group C received magnesium
      sulfate (50 mg/kg), group D received both valium (0.1 mg/kg) and magnesium
      sulfate (50 mg/kg). The control (group A) received neither valium nor magnesium
      sulfate. Local anesthetic toxicity was observed and recorded in all the groups.
      RESULTS: Local anesthetic toxicity was significantly decreased in group B and
      group C compared with group A (P<0.05), and the toxicity was even more
      significantly decreased in group D(P<0.01 vs group A). CONCLUSION: Local
      anesthetic toxicity of sacral block can be significantly decreased by intravenous
      injection of valium or magnesium sulfate, and their combination produces stronger
      effects.

PMID- 15501742
TI  - [Management of hyperkalemia-induced cardiac arrest in anhepatic stage of
      orthotopic liver transplantation without venovenous bypass: report of 3 cases].
AB  - The causes of high serum potassium-induced cardiac arrest in anhepatic stage of
      orthotopic liver transplantation were analyzed in 3 cases without venovenous
      bypass, and the effectiveness of insulin was evaluated in correcting hyperkalemia
      during the anhepatic stage. To improve the survival rate of patients with such
      cardiac arrest, early cardiopulmonary resuscitation and timely defibrillation
      should be performed.

PMID- 15501743
TI  - New concepts in antibody-mediated immunity.

PMID- 15501744
TI  - The fibrinogen receptor FbsA promotes adherence of Streptococcus agalactiae to
      human epithelial cells.
AB  - Streptococcus agalactiae is a major cause of bacterial pneumonia, sepsis, and
      meningitis in human neonates. During the course of infection, S. agalactiae
      adheres to a variety of epithelial cells but the underlying mechanisms are only
      poorly understood. The present report demonstrates the importance of the
      fibrinogen receptor FbsA for the streptococcal adherence and invasion of
      epithelial cells. Deletion of the fbsA gene in various S. agalactiae strains
      substantially reduced their binding of soluble fibrinogen and their adherence to
      and invasion of epithelial cells, indicating a role of FbsA in these different
      processes. The adherence and invasiveness of an fbsA deletion mutant were
      partially restored by reintroducing the fbsA gene on an expression vector.
      Heterologous expression of fbsA in Lactococcus lactis enabled this bacterium to
      adhere to but not to invade epithelial cells, suggesting that FbsA is a
      streptococcal adhesin. Flow cytometry experiments revealed a dose-dependent
      binding of FbsA to the surface of epithelial cells. Furthermore, tissue culture
      experiments exhibited an intimate contact of FbsA-coated latex beads with the
      surfaces of human epithelial cells. Finally, host cell adherence and invasion
      were significantly blocked in competition experiments with either purified FbsA
      protein or a monoclonal antibody directed against the fibrinogen-binding epitope
      of FbsA. Taken together, our studies demonstrate that FbsA promotes the adherence
      of S. agalactiae to epithelial cells but that FbsA does not mediate the bacterial
      invasion into host cells. Our results also indicate that fibrinogen-binding
      epitopes within FbsA are involved in the adherence of S. agalactiae to epithelial
      cells.

PMID- 15501745
TI  - Regulation of Candida albicans morphogenesis by fatty acid metabolites.
AB  - Candida albicans is an opportunistic dimorphic fungus that inhabits various host
      mucosal sites. Conversion from the yeast to the hyphal form has been associated
      with increased virulence and mucosal invasiveness. C. albicans morphogenesis is
      regulated by multiple signals and signaling pathways. However, signals that
      control morphogenesis in vivo are unknown. We investigated the effects of host
      long chain fatty acids, eicosanoids, and bacterial short chain fatty acids on
      control of germination. None of the C18 or C20 fatty acids tested had an effect
      on enhancing germ tube formation (arachidonic acid, oleic acid, linolenic acid,
      or gamma-linolenic acid). Among the different eicosanoids, both prostaglandin E2
      and thromboxane B2 significantly enhanced serum-induced germination by C.
      albicans. Addition of antiprostaglandin or antithromboxane antibodies to serum
      alone inhibited germ tube formation by almost 30%, while control antibody had no
      effect, indicating that these eicosanoids are major morphogenic factors in the
      serum. Since these molecules also bind to albumin, this may also explain the
      hyphal transforming activity in serum that associates with albumin.
      Interestingly, short chain fatty acids (butyric acid), the product of lactic acid
      bacteria (LAB), inhibited germination. In addition, LAB culture supernatants as
      well as live LAB also inhibited C. albicans morphogenesis. Overall, these results
      indicate that fatty acid metabolites and fatty acid pathways can up-regulate and
      down-regulate germination in C. albicans.

PMID- 15501746
TI  - Passive immunization of neonatal mice against Pneumocystis carinii f. sp. muris
      enhances control of infection without stimulating inflammation.
AB  - Pneumocystis carinii is an opportunistic fungal pathogen that causes life
      threatening pneumonia in immunocompromised individuals. Infants appear to be
      particularly susceptible to infection with Pneumocystis. We have previously shown
      that there is a significant delay in clearance of the organisms from the lungs of
      neonatal mice compared to adults. Since alveolar macrophages are the effector
      cells responsible for killing and clearance of Pneumocystis, we have examined
      alveolar macrophage activity in neonatal mice. We found that alveolar macrophage
      activation is delayed about 1 week in Pneumocystis-infected neonates compared to
      adults. Opsonization of the organism by Pneumocystis-specific antibody resulted
      in increased clearance of the organism in neonatal mice; however, there was
      decreased expression of activation markers on neonatal alveolar macrophages and
      reduced levels of cytokines associated with macrophage activation. Mice born to
      immunized dams had significant amounts of Pneumocystis-specific immunoglobulin G
      in their lungs and serum at day 7 postinfection, whereas mice born to naive dams
      had merely detectable levels. This difference correlated with enhanced
      Pneumocystis clearance in mice born to immunized dams. The increase in specific
      antibody, however, did not result in significant inflammation in the lungs, as no
      differences in numbers of activated CD4+ cells were observed. Furthermore, there
      was no difference in cytokine or chemokine concentrations in the lungs of pups
      born to immune compared to naive dams. These findings indicate that specific
      antibody plays an important role in Pneumocystis clearance from lungs of infected
      neonates; moreover, this process occurs without inducing inflammation in the
      lungs.

PMID- 15501747
TI  - Macrophages from mice with the restrictive Lgn1 allele exhibit multifactorial
      resistance to Legionella pneumophila.
AB  - Although Legionella pneumophila can multiply in diverse cell types from a variety
      of species, macrophages from most inbred mouse strains are nonpermissive for
      intracellular replication and allow little or no growth of the bacteria. This
      phenomenon is likely genetically controlled by the mouse naip5 (birc1e) gene
      located within the Lgn1 locus. In this study, we have investigated the resistance
      of C57BL/6J macrophages to L. pneumophila infection by examining the fate of both
      the bacterium and the infected cells compared to that in macrophages from the
      permissive A/J strain. Our results indicate that although the trafficking of the
      L. pneumophila-containing vacuole is partially disrupted in C57BL/6J macrophages,
      this cannot account for the severity of the defect in intracellular growth
      observed in this strain. Infected macrophages are lost shortly after infection,
      and at later times a larger fraction of the C57BL/6J macrophages in which L.
      pneumophila undergoes replication are apoptotic compared to those derived from
      A/J mice. Finally, a loss of bacterial counts occurs after the first round of
      growth. Therefore, the resistance mechanism of C57BL/6J macrophages to L.
      pneumophila infection appears to be multifactorial, and we discuss how early and
      late responses result in clearing the infection.

PMID- 15501748
TI  - Cell wall mannan and cell surface hydrophobicity in Candida albicans serotype A
      and B strains.
AB  - Cell surface hydrophobicity contributes to the pathogenesis of the opportunistic
      fungal pathogen Candida albicans. Previous work demonstrated a correlation
      between hydrophobicity status and changes in the acid-labile, phosphodiester
      linked beta-1,2-oligomannoside components of the N-linked glycans of cell wall
      mannoprotein. Glycan composition also defines the two major serotypes, A and B,
      of C. albicans strains. Here, we show that the cell surface hydrophobicity of the
      two serotypes is qualitatively different, suggesting that the serotypes may
      differ in how they modulate cell surface hydrophobicity status. The cell wall
      mannoproteins from hydrophilic and hydrophobic cells of both serotypes were
      compared to determine whether the glycan differences due to serotype affect the
      glycan differences due to hydrophobicity status. Composition analysis showed that
      the protein, hexose, and phosphate contents of the mannoprotein fraction did not
      differ significantly among the strains tested. Electrophoretic profiles of the
      acid-labile mannan differed only with hydrophobicity status, not serotype, though
      some strain-specific differences were observed. Furthermore, a newly available
      beta-1,2-oligomannoside ladder allowed unambiguous identification of acid-labile
      mannan components. Finally, to assess whether the acid-stable mannan also affects
      cell surface hydrophobicity status, this fraction was fragmented into its
      component branches by acetolysis. The electrophoretic profiles of the acid-stable
      branches were very similar regardless of hydrophobicity status. However,
      differences were observed between serotypes. These results support and extend our
      current model that modification of the acid-labile beta-1,2-oligomannoside chain
      length but not modification of the acid-stable region is one common mechanism by
      which switching of cell surface hydrophobicity status of C. albicans strains
      occurs.

PMID- 15501749
TI  - SdrX, a serine-aspartate repeat protein expressed by Staphylococcus capitis with
      collagen VI binding activity.
AB  - Staphylococcus capitis (S. capitis) has been implicated in a large proportion of
      coagulase-negative staphylococcal infections in very-low-birth-weight infants. To
      identify potential therapeutic targets, the S. capitis genome was probed for the
      presence of genes encoding microbial surface components recognizing adhesive
      matrix molecules (MSCRAMM). By using Southern blot analysis, an S. capitis gene,
      designated sdrX, that contained sequence motifs consistent with the Sdr family of
      MSCRAMM proteins was identified. By using monospecific antisera in Western blot
      and flow cytometry, SdrX was demonstrated to be expressed on the surface of S.
      capitis. Human collagen type VI was found to bind both the recombinant A domain
      of SdrX and viable S. capitis expressing SdrX. SdrX is the first collagen-binding
      Sdr protein described and is the first MSCRAMM protein identified in S. capitis.

PMID- 15501750
TI  - Utility of the Trypanosoma cruzi sequence database for identification of
      potential vaccine candidates by in silico and in vitro screening.
AB  - Glycosylphosphatidylinositol (GPI)-anchored proteins are abundantly expressed in
      the infective and intracellular stages of Trypanosoma cruzi and are recognized as
      antigenic targets by both the humoral and cellular arms of the immune system.
      Previously, we demonstrated the efficacy of genes encoding GPI-anchored proteins
      in eliciting partially protective immunity to T. cruzi infection and disease,
      suggesting their utility as vaccine candidates. For the identification of
      additional vaccine targets, in this study we screened the T. cruzi expressed
      sequence tag (EST) and genomic sequence survey (GSS) databases. By applying a
      variety of web-based genome-mining tools to the analysis of approximately 2,500
      sequences, we identified 348 (37.6%) EST and 260 (17.4%) GSS sequences encoding
      novel parasite-specific proteins. Of these, 19 sequences exhibited the
      characteristics of secreted and/or membrane-associated GPI proteins. Eight of the
      selected sequences were amplified to obtain genes TcG1, TcG2, TcG3, TcG4, TcG5,
      TcG6, TcG7, and TcG8 (TcG1-TcG8) which are expressed in different developmental
      stages of the parasite and conserved in the genome of a variety of T. cruzi
      strains. Flow cytometry confirmed the expression of the antigens encoded by the
      cloned genes as surface proteins in trypomastigote and/or amastigote stages of T.
      cruzi. When delivered as a DNA vaccine, genes TcG1-TcG6 elicited a parasite
      specific antibody response in mice. Except for TcG5, antisera to genes TcG1-TcG6
      exhibited trypanolytic activity against the trypomastigote forms of T. cruzi, a
      property known to correlate with the immune control of T. cruzi. Taken together,
      our results validate the applicability of bioinformatics in genome mining,
      resulting in the identification of T. cruzi membrane-associated proteins that are
      potential vaccine candidates.

PMID- 15501751
TI  - Recognition of mycobacterial antigens delivered by genetically detoxified
      Bordetella pertussis adenylate cyclase by T cells from cattle with bovine
      tuberculosis.
AB  - The exponential increase in the incidence of tuberculosis in cattle over the last
      two decades in the British national herd constitutes a significant economic
      problem. Therefore, research efforts are under way to develop cattle tuberculosis
      vaccines and specific diagnostic reagents to allow the distinction of vaccinated
      from infected animals. Mycobacterial antigens like ESAT-6 and CFP10 allow this
      distinction. This study investigates whether fusion protein of ESAT-6 or CFP10
      with genetically detoxified Bordetella pertussis adenylate cyclase (CyaA) are
      recognized by Mycobacterium bovis-infected cattle more effectively than
      conventional recombinant proteins are, thus enhancing sensitivity or reducing the
      amount of antigens required. By measuring the frequencies of gamma interferon
      (IFN-gamma)-producing cells, we were able to show that the presentation of CFP10
      as a CyaA fusion protein enhanced the molecular efficiency of its recognition 20
      fold, while the recognition of ESAT-6 was not improved by CyaA delivery.
      Furthermore, in the whole-blood IFN-gamma test currently used in the field, the
      delivery of CFP10 and ESAT-6 by fusion to CyaA increased the amount of IFN-gamma
      produced and hence the proportion of infected animals responding to CFP10. The
      improved T-cell recognition of CyaA336/CFP10 was found to be dependent upon
      interaction with CD11b. In addition, presentation of CyaA336/CFP10 to CD4+ T
      cells was chloroquine sensitive, and CFP10 delivery by CyaA resulted in its
      accelerated presentation to T cells. In conclusion, the use of CyaA fusion
      proteins with ESAT-6 and CFP10 has the potential to improve the sensitivity of
      immunodiagnostic tests detecting bovine tuberculosis in cattle.

PMID- 15501752
TI  - Expression of type IV pili by Moraxella catarrhalis is essential for natural
      competence and is affected by iron limitation.
AB  - Type IV pili, filamentous surface appendages primarily composed of a single
      protein subunit termed pilin, play a crucial role in the initiation of disease by
      a wide range of pathogenic bacteria. Although previous electron microscopic
      studies suggested that pili might be present on the surface of Moraxella
      catarrhalis isolates, detailed molecular and phenotypic analyses of these
      structures have not been reported to date. We identified and cloned the M.
      catarrhalis genes encoding PilA, the major pilin subunit, PilQ, the outer
      membrane secretin through which the pilus filament is extruded, and PilT, the
      NTPase that mediates pilin disassembly and retraction. To initiate investigation
      of the role of this surface organelle in pathogenesis, isogenic pilA, pilT, and
      pilQ mutants were constructed in M. catarrhalis strain 7169. Comparative analyses
      of the wild-type 7169 strain and three isogenic pil mutants demonstrated that M.
      catarrhalis expresses type IV pili that are essential for natural genetic
      transformation. Our studies suggest type IV pilus production by M. catarrhalis is
      constitutive and ubiquitous, although pilin expression was demonstrated to be
      iron responsive and Fur regulated. These data indicate that additional studies
      aimed at elucidating the prevalence and role of type IV pili in the pathogenesis
      and host response to M. catarrhalis infections are warranted.

PMID- 15501753
TI  - Differential expression of porins OmpP2A and OmpP2B of Haemophilus ducreyi.
AB  - Haemophilus ducreyi is a strict human pathogen and the causative agent of the
      sexually transmitted disease chancroid. The genome of the human-passaged strain
      of H. ducreyi (35000HP) contains two homologous genes whose protein products have
      estimated molecular masses of 46 and 43 kDa. A comparative analysis of the
      deduced amino acid sequences revealed that these proteins share 27 to 33%
      identity to the outer membrane protein P2 (OmpP2), a major porin of Haemophilus
      influenzae. Therefore, these proteins have been designated OmpP2A and OmpP2B,
      respectively. The detection of ompP2A and ompP2B transcripts by reverse
      transcriptase PCR indicated that these genes were independently transcribed in H.
      ducreyi 35000HP. Western blot analysis of outer membrane proteins isolated from a
      geographically diverse collection of H. ducreyi clinical isolates revealed that
      OmpP2A and OmpP2B were differentially expressed among these strains. Although PCR
      analysis suggested that ompP2A and ompP2B were conserved among the strains
      tested, the differential expression observed was due to nucleotide additions and
      partial gene deletions. Purified OmpP2A and OmpP2B were isolated under
      nondenaturing conditions, and subsequent analysis demonstrated that these two
      proteins exhibited porin activity. OmpP2A and OmpP2B are the first porins
      described for H. ducreyi.

PMID- 15501754
TI  - Extracellular secretion of the Borrelia burgdorferi Oms28 porin and Bgp, a
      glycosaminoglycan binding protein.
AB  - Borrelia burgdorferi, the Lyme disease pathogen, cycles between its Ixodes tick
      vector and vertebrate hosts, adapting to vastly different biochemical
      environments. Spirochete gene expression as a function of temperature, pH, growth
      phase, and host milieu is well studied, and recent work suggests that regulatory
      networks are involved. Here, we examine the release of Borrelia burgdorferi
      strain B31 proteins into conditioned medium. Spirochetes intrinsically
      radiolabeled at concentrations ranging from 10(7) to 10(9) cells per ml secreted
      Oms28, a previously characterized outer membrane porin, into RPMI medium. As
      determined by immunoblotting, this secretion was not associated with outer
      membrane blebs or cytoplasmic contamination. A similar profile of secreted
      proteins was obtained for spirochetes radiolabeled in mixtures of RPMI medium and
      serum-free Barbour-Stoenner-Kelly (BSK II) medium. Proteomic liquid
      chromatography-tandem mass spectrometry analysis of tryptic fragments derived
      from strain B31 culture supernatants confirmed the identity of the 28-kDa species
      as Oms28 and revealed a 26-kDa protein as 5'-methylthioadenosine/S
      adenosylhomocysteine nucleosidase (Pfs-2), previously described as Bgp, a
      glycosaminoglycan-binding protein. The release of Oms28 into the culture medium
      is more selective when the spirochetes are in logarithmic phase of growth
      compared to organisms obtained from stationary phase. As determined by
      immunoblotting, stationary-phase spirochetes released OspA, OspB, and flagellin.
      Oms28 secreted by strains B31, HB19, and N40 was also recovered by
      radioimmunoprecipitation. This is the first report of B. burgdorferi protein
      secretion into the extracellular environment. The possible roles of Oms28 and Bgp
      in the host-pathogen interaction are considered.

PMID- 15501755
TI  - Interleukin-10 (IL-10) counterregulates IL-4-dependent effector mechanisms in
      Murine Filariasis.
AB  - Interleukin-10 (IL-10) was at first described as a Th2-associated cytokine,
      although more recent reports have shown that immunosuppression applies to both
      Th1 and Th2 cell responses, e.g., when produced by T regulatory cells. This
      concept when applied to human filariasis would argue that high parasite loads are
      associated with IL-10, while bona fide Th2 responses, mediated by IL-4, IL-5, and
      IL-13, are associated with parasite containment. To prove this relationship in a
      causal manner, we investigated the roles of IL-4 and IL-10 in a helminth
      infection model in which mice genetically deficient for IL-4, IL-10, or IL-4 plus
      IL-10 were infected with the rodent filaria Litomosoides sigmodontis. Compared to
      C57BL/6 wild-type and IL-10 knockout (KO) mice, IL-4 KO mice remained
      susceptible, exhibiting a remarkable number of live adult worms. Interestingly
      however, when the IL-10 gene was knocked out simultaneously with the IL-4 gene,
      the susceptibility of IL-4 KO mice was reversed. Although production of IFN-gamma
      was increased in IL-4/IL-10 double-knockout mice, depletion of gamma interferon
      did not affect worm elimination, so it seems unlikely to be the major factor in
      mediating resistance in IL-4/IL-10 KO mice. Taken together, the results of this
      study add proof to the concept that has arisen for human filariasis that IL-10
      dependent responses, which are associated with patency, are antagonistic to bona
      fide Th2 responses, which control parasite loads. The finding that knockout of IL
      10 reversed a disease phenotype induced by knockout of IL-4 gives the first
      causal evidence of an antagonistic activity between IL-4 and IL-10 in an
      infection in vivo.

PMID- 15501756
TI  - Respiratory hydrogen use by Salmonella enterica serovar Typhimurium is essential
      for virulence.
AB  - Based on available annotated gene sequence information, the enteric pathogen
      salmonella, like other enteric bacteria, contains three putative membrane
      associated H2-using hydrogenase enzymes. These enzymes split molecular H2,
      releasing low-potential electrons that are used to reduce quinone or heme
      containing components of the respiratory chain. Here we show that each of the
      three distinct membrane-associated hydrogenases of Salmonella enterica serovar
      Typhimurium is coupled to a respiratory pathway that uses oxygen as the terminal
      electron acceptor. Cells grown in a blood-based medium expressed four times the
      amount of hydrogenase (H2 oxidation) activity that cells grown on Luria Bertani
      medium did. Cells suspended in phosphate-buffered saline consumed 2 mol of H2 per
      mol of O2 used in the H2-O2 respiratory pathway, and the activity was inhibited
      by the respiration inhibitor cyanide. Molecular hydrogen levels averaging over 40
      microM were measured in organs (i.e., livers and spleens) of live mice, and
      levels within the intestinal tract (the presumed origin of the gas) were four
      times greater than this. The half-saturation affinity of S. enterica serovar
      Typhimurium for H2 is only 2.1 microM, so it is expected that H2-utilizing
      hydrogenase enzymes are saturated with the reducing substrate in vivo. All three
      hydrogenase enzymes contribute to the virulence of the bacterium in a typhoid
      fever-mouse model, based on results from strains with mutations in each of the
      three hydrogenase genes. The introduced mutations are nonpolar, and growth of the
      mutant strains was like that of the parent strain. The combined removal of all
      three hydrogenases resulted in a strain that is avirulent and (in contrast to the
      parent strain) one that is unable to invade liver or spleen tissue. The
      introduction of one of the hydrogenase genes into the triple mutant strain on a
      low-copy-number plasmid resulted in a strain that was able to both oxidize H2 and
      cause morbidity in mice within 11 days of inoculation; therefore, the avirulent
      phenotype of the triple mutant is not due to an unknown spurious mutation. We
      conclude that H2 utilization in a respiratory fashion is required for energy
      production to permit salmonella growth and subsequent virulence during infection.

PMID- 15501757
TI  - Strain-specific humoral response to a polymorphic malaria vaccine.
AB  - The 3D7 form of the merozoite surface protein 2 (MSP2) of Plasmodium falciparum
      was one of three subunits of the malaria vaccine Combination B that were tested
      in a phase I/IIb double-blind randomized placebo-controlled trial, which was
      undertaken with 120 Papua New Guinean children of 5 to 9 years of age. Because
      only one variant of the highly polymorphic MSP2 was used for vaccination, we
      examined whether the elicited response was directed against conserved or strain
      specific epitopes. Postvaccination (week 12) titers of antibody against
      recombinantly expressed individual domains of MSP2 were measured by enzyme-linked
      immunosorbent assay and compared to baseline values. We found that vaccination
      with the 3D7 form of MSP2 induced a significant strain-specific humoral response
      directed against the repetitive and semiconserved family-specific part. The
      conserved N- and C-terminal domains were not immunogenic. Titers of antibody
      against the alternate FC27 family-specific domain showed a tendency to increase
      in vaccinated children, but there was no increase in antibodies against FC27-type
      32-mer repeats. These results indicate that vaccination with one MSP2 variant
      mainly induced a strain-specific response, which can explain the selective effect
      of vaccination with combination B on the genotypes of breakthrough parasites.
      These findings support the inclusion of both family-specific domains (3D7 and
      FC27) in an improved vaccine formulation.

PMID- 15501758
TI  - Mycobacterium marinum strains can be divided into two distinct types based on
      genetic diversity and virulence.
AB  - Mycobacterium marinum causes a systemic tuberculosis-like disease in a large
      number of poikilothermic animals and is used as a model for mycobacterial
      pathogenesis. In the present study, we infected zebra fish (Danio rerio) with
      different strains of M. marinum to determine the variation in pathogenicity.
      Depending on the M. marinum isolate, the fish developed an acute or chronic
      disease. Acute disease was characterized by uncontrolled growth of the pathogen
      and death of all animals within 16 days, whereas chronic disease was
      characterized by granuloma formation in different organs and survival of the
      animals for at least 4 to 8 weeks. Genetic analysis of the isolates by amplified
      fragment length polymorphism showed that M. marinum strains could be divided in
      two clusters. Cluster I contained predominantly strains isolated from humans with
      fish tank granuloma, whereas the majority of the cluster II strains were isolated
      from poikilothermic species. Acute disease progression was noted only with
      strains belonging to cluster I, whereas all chronic-disease-causing isolates
      belonged to cluster II. This difference in virulence was also observed in vitro:
      cluster I isolate Mma20 was able to infect and survive more efficiently in the
      human macrophage THP-1 and the carp leukocyte CLC cell lines than was the cluster
      II isolate Mma11. We conclude that strain characteristics play an important role
      in the pathogenicity of M. marinum. In addition, the correlation between genetic
      variation and host origin suggests that cluster I isolates are more pathogenic
      for humans.

PMID- 15501759
TI  - Functional analysis of Bacillus anthracis protective antigen by using
      neutralizing monoclonal antibodies.
AB  - Protective antigen (PA) is central to the action of the lethal and edema toxins
      produced by Bacillus anthracis. It is the common cell-binding component,
      mediating the translocation of the enzymatic moieties (lethal factor [LF] and
      edema factor) into the cytoplasm of the host cell. Monoclonal antibodies (MAbs)
      against PA, able to neutralize the activities of the toxins in vitro and in vivo,
      were screened. Two such MAbs, named 7.5 and 48.3, were purified and further
      characterized. MAb 7.5 binds to domain 4 of PA and prevents the binding of PA to
      its cell receptor. MAb 48.3 binds to domain 2 and blocks the cleavage of PA into
      PA63, a step necessary for the subsequent interaction with the enzymatic
      moieties. The epitope recognized by this antibody is in a region involved in the
      oligomerization of PA63; thus, MAb 48.3 does not recognize the oligomer form.
      MAbs 7.5 and 48.3 neutralize the activities of anthrax toxins produced by B.
      anthracis in mice. Also, there is an additive effect between the two MAbs against
      PA and a MAb against LF, in protecting mice against a lethal challenge by the
      Sterne strain. This work contributes to the functional analysis of PA and offers
      immunotherapeutic perspectives for the treatment of anthrax disease.

PMID- 15501760
TI  - Antimycobacterial calixarenes enhance innate defense mechanisms in murine
      macrophages and induce control of Mycobacterium tuberculosis infection in mice.
AB  - Tuberculosis remains the leading cause of death among infectious diseases,
      accounting for more than two million deaths annually. The incidence of the
      disease is increasing globally, partially because of the resurgence of drug
      resistant strains of Mycobacterium tuberculosis. Calixarenes are macrocyclic
      oligomers, some of which are able to modify the growth of M. tuberculosis in
      infected cells. Most experimental work has been carried out with Macrocyclon,
      also known as HOC 12.5EO. In this study, we demonstrate that Macrocyclon is
      effective in controlling M. tuberculosis infections, and we provide evidence that
      its effect is partially mediated by an l-arginine-dependent mechanism of
      macrophage activation that involves the activity of the inducible nitric oxide
      synthase. We also show that Macrocyclon is effective in athymic and major
      histocompatibility complex class II-/- mice and synthesized a number of
      structurally related calixarenes expressing significant antimycobacterial
      activity.

PMID- 15501761
TI  - RNA encoding the MPT83 antigen induces protective immune responses against
      Mycobacterium tuberculosis infection.
AB  - We have previously demonstrated that vaccination of mice with plasmid DNA vectors
      expressing immunodominant mycobacterial genes induced cellular immune responses
      and significant protection against challenge with Mycobacterium tuberculosis. We
      demonstrate here, using in vitro-synthesized RNA, that vaccination with DNA or
      RNA constructs expressing the M. tuberculosis MPT83 antigen are capable of
      inducing specific humoral and T-cell immune responses and confer modest but
      significant protection against M. tuberculosis challenge in mice. This is the
      first report of protective immunity conferred against intracellular bacteria by
      an RNA vaccine. This novel approach avoids some of the drawbacks of DNA vaccines
      and illustrates the potential for developing new antimycobacterial immunization
      strategies.

PMID- 15501762
TI  - The infecting dose of Chlamydia muridarum modulates the innate immune response
      and ascending infection.
AB  - Murine vaginal infection with the obligate intracellular bacterium Chlamydia
      muridarum is commonly used as a model for ascending Chlamydia infections of the
      human female genital tract. Gamma interferon-producing Th1 cells, in concert with
      other mononuclear infiltrates, primarily mediate antichlamydial immunity.
      However, many factors modify this response, including the bacterial load. To
      investigate the manner in which the inoculating dose of C. muridarum modulates a
      genital infection, we measured innate and adaptive cell numbers, CD4+ lymphocyte
      cytokine profile, chemokine expression, course of infection, and pathological
      sequelae in genital tracts of BALB/c mice infected with doses of C. muridarum
      ranging from 10(4) to 10(7) inclusion-forming units. We found that the influx of
      both innate and adaptive immune cells responded similarly in the lower genital
      tract (cervical-vaginal tissues) and upper genital tract (oviduct tissues) to
      increasing inoculating doses. However, cells expressing the innate markers Gr-1
      and CD11c were affected to a greater degree by increasing dose than lymphocytes
      of the adaptive immune response (Th1, CD4+, CD8+, CD19+), resulting in a change
      in the balance of innate and adaptive cell numbers to favor innate cells at
      higher infecting doses. Surprisingly, we detected greater numbers of viable
      chlamydiae in the oviducts at lower inoculating doses, and the number of
      organisms appeared to directly correlate with hydrosalpinx formation after both
      primary infection and repeat infection. Taken together, these data suggest that
      innate immune cells contribute to control of ascending infection.

PMID- 15501763
TI  - Glycosylation of the major polar tube protein of Encephalitozoon hellem, a
      microsporidian parasite that infects humans.
AB  - The microsporidia are ubiquitous, obligate intracellular eukaryotic spore-forming
      parasites infecting a wide range of invertebrates and vertebrates, including
      humans. The defining structure of microsporidia is the polar tube, which forms a
      hollow tube through which the sporoplasm is transferred to the host cell.
      Research on the molecular and cellular biology of the polar tube has resulted in
      the identification of three polar tube proteins: PTP1, PTP2, and PTP3. The major
      polar tube protein, PTP1, accounts for at least 70% of the mass of the polar
      tube. In the present study, PTP1 was found to be posttranslationally modified.
      Concanavalin A (ConA) bound to PTP1 and to the polar tube of several different
      microsporidia species. Analysis of the glycosylation of Encephalitozoon hellem
      PTP1 suggested that it is modified by O-linked mannosylation, and ConA binds to
      these O-linked mannose residues. Mannose pretreatment of RK13 host cells
      decreased their infection by E. hellem, consistent with an interaction between
      the mannosylation of PTP1 and some unknown host cell mannose-binding molecule. A
      CHO cell line (Lec1) that is unable to synthesize complex-type N-linked
      oligosaccharides had an increased susceptibility to E. hellem infection compared
      to wild-type CHO cells. These data suggest that the O-mannosylation of PTP1 may
      have functional significance for the ability of microsporidia to invade their
      host cells.

PMID- 15501764
TI  - The Type II heat-labile enterotoxins LT-IIa and LT-IIb and their respective B
      pentamers differentially induce and regulate cytokine production in human
      monocytic cells.
AB  - The type II heat-labile enterotoxins, LT-IIa and LT-IIb, exhibit potent adjuvant
      properties. However, little is known about their immunomodulatory activities upon
      interaction with innate immune cells, unlike the widely studied type I
      enterotoxins that include cholera toxin (CT). We therefore investigated
      interactions of LT-IIa and LT-IIb with human monocytic THP-1 cells. We found that
      LT-II enterotoxins were inactive in stimulating cytokine release, whereas CT
      induced low levels of interleukin-1beta (IL-1beta) and IL-8. However, all three
      enterotoxins potently regulated cytokine induction in cells activated by
      bacterial lipopolysaccharide or fimbriae. Induction of proinflammatory (tumor
      necrosis factor alpha [TNF-alpha]) or chemotactic (IL-8) cytokines was
      downregulated, whereas induction of cytokines with anti-inflammatory (IL-10) or
      mucosal adjuvant properties (IL-1beta) was upregulated by the enterotoxins. These
      effects appeared to depend on their A subunits, because isolated B-pentameric
      subunits lacked regulatory activity. Enterotoxin-mediated inhibition of
      proinflammatory cytokine induction in activated cells was partially attributable
      to synergism for endogenous production of IL-10 and to an IL-10-independent
      inhibition of nuclear factor kappaB (NF-kappaB) activation. In sharp contrast to
      the holotoxins, the B pentamers (LT-IIaB and, to a greater extent, LT-IIbB)
      stimulated cytokine production, suggesting a link between the absence of the A
      subunit and increased proinflammatory properties. In this regard, the ability of
      LT-IIbB to activate NF-kappaB and induce TNF-alpha and IL-8 was antagonized by
      the LT-IIb holotoxin. These findings support distinct immunomodulatory roles for
      the LT-II holotoxins and their respective B pentamers. Moreover, the anti
      inflammatory properties of the holotoxins may serve to suppress innate immunity
      and promote the survival of the pathogen.

PMID- 15501765
TI  - Suppression of Plasmodium chabaudi parasitemia is independent of the action of
      reactive oxygen intermediates and/or nitric oxide.
AB  - The killing of blood-stage malaria parasites in vivo has been attributed to
      reactive intermediates of oxygen (ROI) and of nitrogen (RNI). However, in the
      case of the latter, this contention is challenged by recent observations that
      parasitemia was not exacerbated in nitric oxide synthase (NOS) knockout (KO)
      (NOS2-/- or NOS3-/-) mice or in mice treated with NOS inhibitors. We now report
      that the time course shows that Plasmodium chabaudi parasitemia in NADPH oxidase
      KO (p47phox-/-) mice also was not exacerbated, suggesting a minimal role for ROI
      mediated killing of blood-stage parasites. It is possible that the production of
      protective antibodies during malaria may mask the function of ROI and/or RNI.
      However, parasitemia in B-cell-deficient JH-/- x NOS2-/- or JH-/- x p47phox-/-
      mice was not exacerbated. In contrast, the magnitude of peak parasitemia was
      significantly enhanced in p47phox-/- mice treated with the xanthine oxidase
      inhibitor allopurinol, but the duration of patent parasitemia was not prolonged.
      Whereas the time course of parasitemia in NOS2-/- x p47phox-/- mice was nearly
      identical to that seen in normal control mice, allopurinol treatment of these
      double-KO mice also enhanced the magnitude of peak parasitemia. Thus, ROI
      generated via the xanthine oxidase pathway contribute to the control of ascending
      P. chabaudi parasitemia during acute malaria but alone are insufficient to
      suppress parasitemia to subpatent levels. Together, these results indicate that
      ROI or RNI can contribute to, but are not essential for, the suppression of
      parasitemia during blood-stage malaria.

PMID- 15501766
TI  - Glucuronoxylomannan, the major capsular polysaccharide of Cryptococcus
      neoformans, inhibits the progression of group B streptococcal arthritis.
AB  - Glucuronoxylomannan (GXM), the principal constituent of the Cryptococcus
      neoformans capsule, modulates the inflammatory response of human monocytes in
      vitro. Here we examine the efficacy of GXM as a novel anti-inflammatory compound
      for use against experimental septic arthritis. Arthritis was induced in mice by
      the intravenous injection of 8 x 10(6) CFU of type IV group B streptococcus
      (GBS). GXM was administered intravenously in different doses (50, 100, or 200
      microg/mouse) 1 day before and 1 day after bacterial inoculation. GXM treatment
      markedly decreased the incidence and severity of articular lesions. Histological
      findings showed limited periarticular inflammation in the joints of GXM-treated
      mice, confirming the clinical observations. The amelioration of arthritis was
      associated with a significant reduction in the local production of interleukin-6
      (IL-6), IL-1beta, macrophage inflammatory protein 1alpha (MIP-1alpha), and MIP-2
      and an increase in systemic IL-10 levels. Moreover, peritoneal macrophages
      derived from GXM-treated mice and stimulated in vitro with heat-inactivated GBS
      showed a similar pattern of cytokine production. The present study provides
      evidence for the modulation of the inflammatory response by GXM in vivo and
      suggests a potential therapeutic use for this compound in pathologies involving
      inflammatory processes.

PMID- 15501767
TI  - Transcriptome of uropathogenic Escherichia coli during urinary tract infection.
AB  - A uropathogenic Escherichia coli strain CFT073-specific DNA microarray that
      includes each open reading frame was used to analyze the transcriptome of CFT073
      bacteria isolated directly from the urine of infected CBA/J mice. The in vivo
      expression profiles were compared to that of E. coli CFT073 grown statically to
      exponential phase in rich medium, revealing the strategies this pathogen uses in
      vivo for colonization, growth, and survival in the urinary tract environment. The
      most highly expressed genes overall in vivo encoded translational machinery,
      indicating that the bacteria were in a rapid growth state despite specific
      nutrient limitations. Expression of type 1 fimbriae, a virulence factor involved
      in adherence, was highly upregulated in vivo. Five iron acquisition systems were
      all highly upregulated during urinary tract infection, as were genes responsible
      for capsular polysaccharide and lipopolysaccharide synthesis, drug resistance,
      and microcin secretion. Surprisingly, other fimbrial genes, such as pap and
      foc/sfa, and genes involved in motility and chemotaxis were downregulated in
      vivo. E. coli CFT073 grown in human urine resulted in the upregulation of iron
      acquisition, capsule, and microcin secretion genes, thus partially mimicking
      growth in vivo. On the basis of gene expression levels, the urinary tract appears
      to be nitrogen and iron limiting, of high osmolarity, and of moderate
      oxygenation. This study represents the first assessment of any E. coli
      pathotype's transcriptome in vivo and provides specific insights into the
      mechanisms necessary for urinary tract pathogenesis.

PMID- 15501768
TI  - Cytokine response to infection with Bacillus anthracis spores.
AB  - Bacillus anthracis, the etiological agent of anthrax, is a gram-positive, spore
      forming bacterium. The inhalational form of anthrax is the most severe and is
      associated with rapid progression of the disease and the outcome is frequently
      fatal. Transfer from the respiratory epithelium to regional lymph nodes appears
      to be an essential early step in the establishment of infection. This transfer is
      believed to occur by means of carriage within alveolar macrophages following
      phagocytosis. Therefore, the ability of B. anthracis to transit through the host
      macrophage or dendritic cell appears to be an early and critical step in B.
      anthracis pathogenesis. In this work, we examined the cytokine responses to spore
      infection in mouse primary peritoneal macrophages, in primary human dendritic
      cells, and during a spore aerosol infection model utilizing the susceptible A/J
      mouse strain. We demonstrated that both mouse peritoneal macrophages and human
      dendritic cells exhibited significant intracellular bactericidal activity during
      the first hours following uptake, providing the necessary time to mount a
      cytokine response prior to cell lysis. Strong tumor necrosis factor (TNF-alpha)
      and interleukin-6 (IL-6) responses were seen in mouse peritoneal macrophages. In
      addition to TNF-alpha and IL-6, human dendritic cells produced the cytokines IL
      1beta, IL-8, and IL-12. A mixture of Th1 and Th2 cytokines were detected in sera
      obtained from infected animals. In this study, we provide further evidence of an
      acute cytokine response when cells in culture and mice are infected with B.
      anthracis spores.

PMID- 15501769
TI  - In vivo compartmentalization of functionally distinct, rapidly responsive antigen
      specific T-cell populations in DNA-immunized or Salmonella enterica serovar
      Typhimurium-infected mice.
AB  - The location and functional properties of antigen-specific memory T-cell
      populations in lymphoid and nonlymphoid compartments following DNA immunization
      or infection with Salmonella were investigated. Epitope-specific CD8+ -T-cell
      expansion and retention during the memory phase were analyzed for DNA-immunized
      mice by use of a 5-h peptide restimulation assay. These data revealed that
      epitope-specific gamma interferon (IFN-gamma)-positive CD8+ T cells occur at
      higher frequencies in the spleen, liver, and blood than in draining or peripheral
      lymph nodes during the expansion phase. Moreover, this distribution is maintained
      into long-term memory. The location and function of both CD4+ and CD8+ Salmonella
      specific memory T cells in mice who were given a single dose of Salmonella
      enterica serovar Typhimurium was also quantitated by an ex vivo restimulation
      with bacterial lysate to detect the total Salmonella-specific memory pool. Mice
      immunized up to 6 months previously with S. enterica serovar Typhimurium had
      bacterium-specific CD4+ T cells that were capable of producing IFN-gamma or tumor
      necrosis factor alpha (TNF-alpha) at each site analyzed. Similar findings were
      observed for CD8+ T cells that were capable of producing IFN-gamma, while a much
      lower frequency and more restricted distribution were associated with TNF-alpha
      producing CD8+ T cells. This study is the first to assess the frequencies,
      locations, and functions of both CD4+ and CD8+ memory T-cell populations in the
      same Salmonella-infected individuals and demonstrates the organ-specific
      functional compartmentalization of memory T cells after Salmonella infection.

PMID- 15501770
TI  - Novel human in vitro system for evaluating antimycobacterial vaccines.
AB  - Major research efforts are directed towards the development of a better
      antimycobacterial vaccine. But progress in the field of tuberculosis vaccine
      development has been hampered by the lack of human in vitro models to assess
      vaccine immunogenicity and efficacy. New candidate vaccines will have to be
      evaluated against the existing Mycobacterium bovis BCG "gold standard." It is
      therefore important to understand the type of immune responses elicited by BCG
      vaccination to enable comparisons with potential new candidates. We used a novel
      human in vitro whole-blood model, which measures immune responses to mycobacteria
      by use of reporter gene-tagged BCG (BCG lux), to study immune responses to BCG
      vaccination in 50 neonates in a setting in Cape Town, Republic of South Africa,
      where tuberculosis is endemic. BCG vaccination significantly reduced growth of
      BCG lux in whole blood (prevaccination median growth ratio [GR], 9.6; range, 1.3
      to 24; postvaccination median GR, 3.9; range, 0.6 to 12.2 [P < 0.0001]). Growth
      of BCG lux was better restricted in vaccinated infants than in unvaccinated age
      matched controls (n = 4). BCG vaccination induced significantly higher gamma
      interferon production in response to BCG lux (P < 0.0001) and to purified protein
      derivative (P = 0.0001). No significant changes in either growth of BCG lux or
      cytokine production occurred in an adult control group (n = 6) over the study
      period. The whole-blood luminescence model detects changes in cellular immune
      responses to mycobacteria induced by BCG vaccination. It is therefore a useful
      new tool in studying the immunogenicity of newly developed vaccine candidates
      prior to large field trials assessing efficacy.

PMID- 15501772
TI  - Listeria monocytogenes-based antibiotic resistance gene-free antigen delivery
      system applicable to other bacterial vectors and DNA vaccines.
AB  - Plasmids represent a powerful tool to rapidly introduce genes into bacteria and
      help them reach high expression levels. In vaccine development, with live vaccine
      vectors, this allows greater flexibility and the ability to induce larger antigen
      amounts through multiple gene copies. However, plasmid retention often requires
      antibiotic resistance markers, the presence of which has been discouraged in
      clinical applications by the Food and Drug Administration. Therefore, we
      developed a Listeria monocytogenes-Escherichia coli shuttle plasmid that is
      retained by complementation of D-alanine racemase-deficient mutant strains both
      in vitro and in vivo. Our technology potentially allows the production of
      antibiotic resistance marker-free DNA vaccines as well as bacterial vaccine
      vectors devoid of engineered antibiotic resistances. As a proof of concept, we
      applied the D-alanine racemase complementation system to our Listeria cancer
      vaccine platform. With a transplantable tumor model, we compared the efficacy of
      the new Listeria vector to that of an established vector containing a
      conventional plasmid carrying a tumor-specific antigen. Both vaccine vector
      systems resulted in long-term regression of established tumors, with no
      significant difference between them. Thus, the Listeria vaccine vector presented
      here potentially complies with Food and Drug Administration regulations and could
      be developed further for clinical use.

PMID- 15501771
TI  - Gonococcal porin IB activates NF-kappaB in human urethral epithelium and
      increases the expression of host antiapoptotic factors.
AB  - Infection of human urethral epithelial cells (UECs) with Neisseria gonorrhoeae
      increases the transcription of several host antiapoptotic genes, including bfl-1,
      cox-2, and c-IAP-2. In order to identify the bacterial factor(s) responsible for
      eliciting these changes, the transcriptional status of apoptotic machinery was
      monitored in UECs challenged with certain gonococcal membrane components.
      Initially, we observed that infection of UECs with gentamicin-killed gonococci
      increased the expression of the antiapoptotic Bcl-2 family member, bfl-1. This
      observation indicated that viable, replicating bacteria are not required for
      induction of antiapoptotic gene expression. Confirming this observation,
      treatment of UECs with purified gonococcal membrane increased the expression of
      bfl-1, cox-2, and c-IAP-2. This finding suggested that a factor or multiple
      factors present in the outer membrane (OM) are responsible for altering UEC
      antiapoptotic gene expression. Interestingly, treatment of UECs with gonococcal
      porin IB (PorB IB), a major constituent of the OM, significantly increased the
      transcription of bfl-1, cox-2, and c-IAP-2. The upregulation of these genes by
      PorB IB was determined to be dependent on NF-kappaB activation, as inhibiting NF
      kappaB blocked induced expression of these genes. This work demonstrates the
      altered expression of host apoptotic factors in response to gonococcal PorB IB
      and supports a model whereby UEC cell death may be modulated as a potential
      mechanism of bacterial survival and proliferation.

PMID- 15501773
TI  - Identification of a hemin utilization protein of Moraxella catarrhalis (HumA).
AB  - Moraxella catarrhalis is a major cause of acute otitis media in young children
      and has also been implicated as an important cause of exacerbations in adults
      with underlying pulmonary disease. Due to the considerable level of antibiotic
      resistance and the high degree of carriage rates in young children, it is likely
      that the incidence of M. catarrhalis infections will continue to rise. M.
      catarrhalis is a strict human respiratory pathogen, and this bacterium uses both
      transferrin and lactoferrin receptors to fulfill the essential iron requirement
      for survival in vivo. However, these are the only described iron acquisition
      systems for this organism. In this report we have demonstrated that M.
      catarrhalis can also utilize hemin as a sole source of iron for growth. In
      addition, we have identified and characterized an outer membrane protein with
      homology (26 to 28% similarity) to other known hemin binding and uptake proteins
      in related gram-negative organisms (i.e., Bordetella and Yersinia spp.). This
      newly described M. catarrhalis protein, termed HumA, is capable of directly
      binding to hemin coupled to a solid-phase matrix. M. catarrhalis HumA expressed
      on the surface of an Escherichia coli hemA-deficient strain (K-12 EB53) is fully
      capable of complementing the defect and thus restoring the ability of this strain
      to grow in the presence of hemin. When M. catarrhalis is grown in the presence of
      hemin, HumA expression is clearly increased as shown by Western blotting with
      polyclonal antiserum developed against a HumA peptide. In addition, growth
      analyses revealed that a HumA-deficient mutant of M. catarrhalis (7169::humA) is
      restricted for growth in the presence of hemin as the sole iron source compared
      to the wild-type strain. We conclude that HumA is an essential component of a
      hemin uptake and utilization system previously undescribed for M. catarrhalis,
      thus providing another mechanism of iron acquisition that may facilitate
      persistent colonization of the mucosal surface.

PMID- 15501774
TI  - RpoS is not central to the general stress response in Borrelia burgdorferi but
      does control expression of one or more essential virulence determinants.
AB  - Borrelia burgdorferi, the Lyme disease spirochete, undergoes dramatic changes in
      antigenic composition as it cycles between its arthropod and mammalian hosts. A
      growing body of evidence suggests that these changes reflect, at least in part,
      the need for spirochetes to adapt to the physiological stresses imposed by abrupt
      changes in environmental conditions and nutrient availability. In many
      microorganisms, global responses are mediated by master regulators such as
      alternative sigma factors, with Escherichia coli RpoS (sigmaS) serving as a
      prototype. The importance of this transcriptional activator in other bacteria,
      coupled with the report by Hubner et al. (A. Hubner, X. Yang, D. M. Nolen, T. G.
      Popova, F. C. Cabello, and M. V. Norgard, Proc. Natl. Acad. Sci. USA 98:12724
      12729, 2001) demonstrating that the borrelial RpoS ortholog controls expression
      of OspC and decorin-binding protein A (DbpA), prompted us to examine more closely
      the roles of RpoS-dependent and -independent differential gene expression in
      physiological adaptation by the Lyme disease spirochete. We observed that B.
      burgdorferi rpoS (rpoSBb) was induced following temperature shift and transcript
      levels were further enhanced by reduced pH (pH 6.8). Using quantitative real-time
      reverse transcription-PCR (RT-PCR), we demonstrated that, in contrast to its
      ortholog (rpoSEc) in Escherichia coli, rpoSBb was expressed at significant levels
      in B. burgdorferi throughout all phases of growth following temperature shift. By
      comparing a B. burgdorferi strain 297 rpoSBb mutant to its wild-type counterpart,
      we determined that RpoSBb was not required for survival following exposure to a
      wide range of environmental stresses (i.e., temperature shift, serum starvation,
      increased osmolality, reactive oxygen intermediates, and increased or reduced
      oxygen tension), although the mutant was more sensitive to extremes of pH. While
      B. burgdorferi strains lacking RpoS were able to survive within intraperitoneal
      dialysis membrane chambers at a level equivalent to that of the wild type, they
      were avirulent in mice. Lastly, RT-PCR analysis of the ospE-ospF-elp paralogous
      lipoprotein families complements earlier findings that many temperature-inducible
      borrelial loci are controlled in an RpoSBb-independent manner. Together, these
      data point to fundamental differences between the role(s) of RpoS in B.
      burgdorferi and that in E. coli. Rather than functioning as a master regulator,
      RpoSBb appears to serve as a stress-responsive activator of a subset of virulence
      determinants that, together with the RpoS-independent, differentially expressed
      regulon, encompass the spirochete's genetic programs required for mammalian host
      adaptation.

PMID- 15501775
TI  - Intact gram-negative Helicobacter pylori, Helicobacter felis, and Helicobacter
      hepaticus bacteria activate innate immunity via toll-like receptor 2 but not toll
      like receptor 4.
AB  - Molecular and genetic studies have demonstrated that members of the Toll-like
      receptor (TLR) family are critical innate immune receptors. TLRs are recognition
      receptors for a diverse group of microbial ligands including bacteria, fungi, and
      viruses. This study demonstrates that distinct TLRs are responsible for the
      recognition of Helicobacter lipopolysaccharide (LPS) versus intact Helicobacter
      bacteria. We show that the cytokine-inducing activity of Helicobacter LPS was
      mediated by TLR4; i.e., TLR4-deficient macrophages were unresponsive to
      Helicobacter pylori LPS. Surprisingly, the cytokine response to whole
      Helicobacter bacteria (H. pylori, H. hepaticus, and H. felis) was mediated not by
      TLR4 but rather by TLR2. Studies of HEK293 transfectants revealed that expression
      of human TLR2 was sufficient to confer responsiveness to intact Helicobacter
      bacteria, but TLR4 transfection was not sufficient. Our studies further suggest
      that cag pathogenicity island genes may modulate the TLR2 agonist activity of H.
      pylori as cagA+ bacteria were more active on a per-cell basis compared to cagA
      mutant bacteria for interleukin-8 (IL-8) cytokine secretion. Consistent with the
      transfection studies, analysis of knockout mice demonstrated that TLR2 was
      required for the cytokine response to intact Helicobacter bacteria. Macrophages
      from both wild-type and TLR4-deficient mice produced a robust cytokine secretion
      response (IL-6 and MCP-1) when stimulated with intact Helicobacter bacteria. In
      contrast, macrophages from TLR2-deficient mice were profoundly unresponsive to
      intact Helicobacter stimulation, failing to secrete cytokines even at high
      (100:1) bacterium-to-macrophage ratios. Our studies suggest that TLR2 may be the
      dominant innate immune receptor for recognition of gastrointestinal Helicobacter
      species.

PMID- 15501776
TI  - Role of protein tyrosine kinase p53/56lyn in diminished lipopolysaccharide
      priming of formylmethionylleucyl- phenylalanine-induced superoxide production in
      human newborn neutrophils.
AB  - Human newborns are more susceptible than adults to bacterial infection. With gram
      negative bacteria, this may be due to a diminished response of newborn leukocytes
      to lipopolysaccharide (LPS). Since protein tyrosine kinase inhibition abolishes
      LPS priming in adult cells, we hypothesized that protein tyrosine kinases may
      have a critical role in LPS priming of polymorphonuclear neutrophils (PMNs) and
      that newborn PMNs may have altered protein tyrosine kinase activities. In the
      present study, we investigated the role of src family protein tyrosine kinases in
      the LPS response of newborn PMNs compared to adult cells. In a respiratory assay,
      the LPS-primed increase in formylmethionylleucylphenylalanine (fMLP)-triggered O2
      release by adult PMNs was greatly decreased by PP1 [4-amino-5-(4-methyphenyl)-7
      (t-butyl)pyrazolo[3,4-d]pyrimidine], a src kinase inhibitor, to the level of
      untreated newborn PMNs, in which LPS failed to prime. LPS activated the src-like
      kinases p59hck (HCK) and p58fgr (FGR) in both adult and newborn PMNs but
      increased the activation of p53/56lyn (LYN) only in adult cells. In newborn PMNs,
      LYN was highly phosphorylated independent of LPS. We evaluated subcellular
      fractions of PMNs and found that the phosphorylated form of LYN was mainly in the
      Triton-extractable, cytosolic fraction in adult PMNs, while in newborn cells it
      was located mainly in Triton-insoluble, granule- and membrane-associated
      fractions. In contrast, the phosphorylated mitogen-activated protein kinases
      ERK1/2 and p38 were mainly detected in the cytosol in both adult and newborn
      PMNs. These data indicate a role for LYN in the regulation of LPS priming. The
      trapping of phosphorylated LYN in the membrane-granule fraction in newborn PMNs
      may contribute to the deficiency of newborn cells in responding to LPS
      stimulation.

PMID- 15501777
TI  - Differential immune modulatory activity of Pseudomonas aeruginosa quorum-sensing
      signal molecules.
AB  - Pseudomonas aeruginosa releases a spectrum of well-regulated virulence factors,
      controlled by intercellular communication (quorum sensing) and mediated through
      the production of small diffusible quorum-sensing signal molecules (QSSM). We
      hypothesize that QSSM may in fact serve a dual purpose, also allowing bacterial
      colonization via their intrinsic immune-modulatory capacity. One class of signal
      molecule, the N-acylhomoserine lactones, has pleiotropic effects on eukaryotic
      cells, particularly those involved in host immunity. In the present study, we
      have determined the comparative effects of two chemically distinct and
      endobronchially detectable QSSM, N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo
      C12-HSL) and 2-heptyl-3-hydroxy-4 (1H)-quinolone or the Pseudomonas quinolone
      signal (PQS), on human leukocytes exposed to a series of stimuli designed to
      detect differential immunological activity in vitro. 3-Oxo-C12-HSL and PQS
      displayed differential effects on the release of interleukin-2 (IL-2) when human
      T cells were activated via the T-cell receptor and CD28 (a costimulatory
      molecule). 3-Oxo-C12-HSL inhibited cell proliferation and IL-2 release; PQS
      inhibited cell proliferation without affecting IL-2 release. Both molecules
      inhibited cell proliferation and the release of IL-2 following mitogen
      stimulation. Furthermore, in the presence of Escherichia coli lipopolysaccharide,
      3-oxo-C12-HSL inhibited tumor necrosis factor alpha release from human monocytes,
      as reported previously (K. Tateda et al., Infect. Immun. 64:37-43, 1996), whereas
      PQS did not inhibit in this assay. These data highlight the presence of two
      differentially active immune modulatory QSSM from P. aeruginosa, which are
      detectable endobronchially and may be active at the host/pathogen interface
      during infection with P. aeruginosa, should the bronchial airway lymphoid tissues
      prove to be accessible to QSSM.

PMID- 15501778
TI  - Application of mycobacterial proteomics to vaccine design: improved protection by
      Mycobacterium bovis BCG prime-Rv3407 DNA boost vaccination against tuberculosis.
AB  - Information from comparative proteome analysis of Mycobacterium tuberculosis and
      Mycobacterium bovis bacillus Calmette-Guerin (BCG) principally allows prediction
      of potential vaccine candidates. Thirty-six M. tuberculosis DNA vaccine
      candidates identified by comparative proteome analysis were evaluated in the
      mouse model for protection against low-dose aerosol M. tuberculosis infection. We
      identified the DNA vaccine candidate Rv3407 as a protective antigen and analyzed
      putative major histocompatibility complex class I epitopes by computational
      predictions and gamma interferon Elispot assays. Importantly, we discovered that
      the DNA vaccine Rv3407 improved the efficacy of BCG vaccination in a heterologous
      prime-boost vaccination protocol. Our data demonstrate the rationale of a
      combination of proteomics, epitope prediction, and broad screening of putative
      antigens for identification of novel DNA vaccine candidates. Furthermore, our
      experiments show that heterologous prime-boost vaccination with a defined antigen
      boost "on top" of a BCG primer provides superior protection against tuberculosis
      over vaccination with BCG alone.

PMID- 15501779
TI  - Combined vaccine regimen based on parenteral priming with a DNA vaccine and
      administration of an oral booster consisting of a recombinant Salmonella enterica
      serovar Typhimurium vaccine strain for immunization against infection with human
      derived enterotoxigenic Escherichia coli strains.
AB  - Repeated evidence has demonstrated that combined primer-booster immunization
      regimens can improve both secreted and humoral immune responses to antigens
      derived from viral, bacterial, and parasitic pathogens. For the present work, we
      evaluated the synergic serum immunoglobulin G (IgG) and fecal IgA antibody
      responses elicited in BALB/c mice who were intramuscularly primed with a DNA
      vaccine, pRECFA, followed by oral boosting with an attenuated Salmonella enterica
      serovar Typhimurium vaccine (HG3) strain, with both vaccines encoding the
      structural subunit (CfaB) of the CFA/I fimbriae produced by human-derived
      enterotoxigenic Escherichia coli (ETEC) strains. The immunological properties of
      the vaccine regimen were evaluated according to the order of the administered
      vaccines, the nature of the oral antigen carrier, the age of the vaccinated
      animals, the interval between the priming and boosting doses, and the amount of
      injected DNA. The production of gamma interferon and the IgG2a subclass in serum
      indicated that mice immunized with the primer-booster regimen developed
      prevailing type 1 T-cell-dependent immune responses. The synergic effect of the
      vaccine regimen on the induced antibody responses was also revealed by its
      ability to block the adhesive properties of CFA/I fimbriae expressed by live
      bacteria, as shown by the inhibition of Caco-2 cell and human erythrocyte
      binding. Moreover, DBA2 newborn mice were protected from lethal challenges with a
      CFA/I+ ETEC strain after the incubation of live bacteria with serum samples
      harvested from mice who were subjected to the primer-booster regimen. We propose,
      therefore, that the DNA primer-Salmonella booster regimen represents an
      alternative for the development of vaccines requiring both mucosal and systemic
      antibody responses for immunological protection.

PMID- 15501780
TI  - Antibodies to the N-terminal block 2 of Plasmodium falciparum merozoite surface
      protein 1 are associated with protection against clinical malaria.
AB  - This longitudinal prospective study shows that antibodies to the N-terminal block
      2 region of the Plasmodium falciparum merozoite surface protein 1 (MSP-1) are
      associated with protection against clinical malaria in an area of stable but
      seasonal malaria transmission of Ghana. Antibodies to the block 2 region of MSP-1
      were measured in a cohort of 280 children before the beginning of the major
      malaria transmission season. The cohort was then actively monitored for malaria,
      clinically and parasitologically, over a period of 17 months. Evidence is
      presented for an association between antibody responses to block 2 and a
      significantly reduced risk of subsequent clinical malaria. Furthermore,
      statistical survival analysis provides new information on the duration of the
      effect over time. The results support a conclusion that the block 2 region of MSP
      1 is a target of protective immunity against P. falciparum and, thus, a promising
      new candidate for the development of a malaria vaccine.

PMID- 15501781
TI  - Development of immunity to serogroup B meningococci during carriage of Neisseria
      meningitidis in a cohort of university students.
AB  - Understanding the basis of protective immunity is a key requirement for the
      development of an effective vaccine against infection with Neisseria meningitidis
      of serogroup B. We have conducted a longitudinal study into the dynamics of
      meningococcal acquisition and carriage in first-year university students. The
      detection of carriage of serogroup B meningococci correlated with an increase in
      detection of serum bactericidal activity (SBA) against both colonizing and
      heterologous serogroup B strains. Once induced, SBA remained high throughout the
      study. Although students showed increases in antibodies reactive with capsular
      polysaccharide and lipopolysaccharide (LPS), these antibody responses were
      transitory, and their decline was not accompanied by a corresponding decline in
      SBA. In contrast, there was a significant correlation between the presence of
      antibodies to the PorA outer membrane protein and SBA against both homologous and
      heterologous strains. SBA induced by a PorA-negative mutant confirmed the
      contribution of PorA to heterologous activity. Increases in SBA against a range
      of serogroup B strains were also observed in students in whom no meningococcal
      carriage was detected. This heterologous protection could not be associated with
      the presence of antibodies reacting with capsule, LPS, PorA, PorB, Rmp, Opa, Opc,
      or pilin, demonstrating that other, as yet unidentified, antigens contribute to
      the development of immunity to serogroup B meningococci. Identification of such
      antigens with the ability to induce an effective cross-reactive bactericidal
      response to a range of strains would be a major step in the production of a
      universally effective vaccine against infections caused by serogroup B
      meningococci.

PMID- 15501782
TI  - Expression of heterologous antigens in commensal Neisseria spp.: preservation of
      conformational epitopes with vaccine potential.
AB  - Commensal neisseriae share with Neisseria meningitidis (meningococcus) a tendency
      towards overproduction of the bacterial outer envelope, leading to the formation
      and release during growth of outer membrane vesicles (OMVs). OMVs from both
      meningococci and commensal neisseriae have shown promise as vaccines to protect
      against meningococcal disease. We report here the successful expression at high
      levels of heterologous proteins in commensal neisseriae and the display, in its
      native conformation, of one meningococcal outer membrane protein vaccine
      candidate, NspA, in OMVs prepared from such a recombinant Neisseria flavescens
      strain. These NspA-containing OMVs conferred protection against otherwise lethal
      intraperitoneal challenge of mice with N. meningitidis serogroup B, and sera
      raised against them mediated opsonophagocytosis of meningococcal strains
      expressing this antigen. This development promises to facilitate the design of
      novel vaccines containing membrane protein antigens that are otherwise difficult
      to present in native conformation that provide cross-protective efficacy in the
      prevention of meningococcal disease.

PMID- 15501783
TI  - Phase I testing of a malaria vaccine composed of hepatitis B virus core particles
      expressing Plasmodium falciparum circumsporozoite epitopes.
AB  - We report the first phase I trial to assess the safety and immunogenicity of a
      malaria vaccine candidate, ICC-1132 (Malarivax), composed of a modified hepatitis
      B virus core protein (HBc) containing minimal epitopes of the Plasmodium
      falciparum circumsporozoite (CS) protein. When expressed in Escherichia coli, the
      recombinant ICC-1132 protein forms virus-like particles that were found to be
      highly immunogenic in preclinical studies of mice and monkeys. Twenty healthy
      adult volunteers received a 20- or a 50-microg dose of alum-adsorbed ICC-1132
      administered intramuscularly at 0, 2, and 6 months. The majority of volunteers in
      the group receiving the 50-microg dose developed antibodies to CS repeats as well
      as to HBc. Malaria-specific T cells that secreted gamma interferon were also
      detected after a single immunization with ICC-1132-alum. These studies support
      ICC-1132 as a promising malaria vaccine candidate for further clinical testing
      using more-potent adjuvant formulations and confirm the potential of modified HBc
      virus-like particles as a delivery platform for vaccines against other human
      pathogens.

PMID- 15501784
TI  - The Streptococcus gordonii surface proteins GspB and Hsa mediate binding to
      sialylated carbohydrate epitopes on the platelet membrane glycoprotein Ibalpha.
AB  - Platelet binding by Streptococcus gordonii strain M99 is dependent on expression
      of the cell wall-anchored glycoprotein GspB. This large cell surface protein is
      exported from the M99 cytoplasm via a dedicated transport system that includes
      SecA2 and SecY2. GspB is highly similar to Hsa, a protein expressed by S.
      gordonii Challis that has been characterized as a sialic acid binding
      hemagglutinin. In this study, we compared the contribution of GspB and Hsa to the
      adherence of S. gordonii to selected glycoproteins. Our results indicate that
      GspB can mediate binding to a variety of sialylated glycoproteins. GspB
      facilitates binding to carbohydrates bearing sialic acid in either alpha(2-3) or
      alpha(2-6) linkages, with a slight preference for alpha(2-3) linkages.
      Furthermore, GspB readily mediates binding to sialic acid residues on immobilized
      glycocalicin, the extracellular portion of the platelet membrane glycoprotein
      (GP) Ibalpha (the ligand binding subunit of the platelet von Willebrand factor
      receptor complex GPIb-IX-V). Although Hsa is required for the binding of S.
      gordonii Challis to sialic acid, most of the Hsa expressed by Challis is retained
      in the cytoplasm. The deficiency in export is due, at least in part, to a
      nonsense mutation in secA2. Hsa export can be enhanced by complementation with
      secA2 from M99, which also results in significantly greater binding to sialylated
      glycoproteins, including glycocalicin. The combined results indicate that GspB
      and Hsa contribute similar binding capabilities to M99 and Challis, respectively,
      but there may be subtle differences in the preferred epitopes to which these
      adhesins bind.

PMID- 15501785
TI  - Modeling the development of acquired clinical immunity to Plasmodium falciparum
      malaria.
AB  - Individuals living in regions where malaria is endemic develop an acquired
      immunity to malaria which enables them to remain asymptomatic while still
      carrying parasites. Field studies indicate that cumulative exposure to a variety
      of diverse Plasmodium parasites is required for the transition from symptomatic
      to asymptomatic malaria. This study used a simulation model of the within-host
      dynamics of P. falciparum to investigate the development of acquired clinical
      immunity under different transmission conditions and levels of parasite
      diversity. Antibodies developed to P. falciparum erythrocyte membrane protein 1
      (PfEMP1), a clonally variant molecule, were assumed to be a key human
      immunological response to P. falciparum infection, along with responses to
      clonally conserved but polymorphic antigens. The time to the development of
      clinical immunity was found to be proportional to parasite diversity and
      inversely proportional to transmission intensity. The effect of early termination
      of symptomatic infections by chemotherapy was investigated and found not to
      inhibit the host's ability to develop acquired immunity. However, the time
      required to achieve this state was approximately double that compared to when no
      treatment was administered. This study demonstrates that an immune response
      primarily targeted against PfEMP1 has the ability to reduce clinical symptoms of
      infections irrespective of whether treatment is administered, supporting its role
      in the development of acquired clinical immunity. The results also illustrate a
      novel use for simulation models of P. falciparum infections, investigation of the
      influence of intervention strategies on the development of naturally acquired
      clinical immunity.

PMID- 15501786
TI  - Enhanced immunogenicity in the murine airway mucosa with an attenuated Salmonella
      live vaccine expressing OprF-OprI from Pseudomonas aeruginosa.
AB  - We constructed an oral live vaccine based on the attenuated aroA mutant
      Salmonella enterica serovar Typhimurium strain SL3261 expressing outer membrane
      proteins F and I (OprF-OprI) from Pseudomonas aeruginosa and investigated it in a
      mouse model. Strains with in vivo inducible protein expression with the PpacC
      promoter showed good infection rates and immunogenicity but failed to engender
      detectable antibodies in the lung. However, a systemic booster vaccination
      following an oral primary immunization yielded high immunoglobulin A (IgA) and
      IgG antibody levels in both upper and lower airways superior to conventional
      systemic or mucosal booster vaccination alone. In addition, the proportion of
      IgG1 and IgG2a antibodies suggested that the systemic booster does not alter the
      more TH1-like type of response induced by the oral Salmonella primary
      vaccination. We conclude that an oral primary systemic booster vaccination
      strategy with an appropriate mucosal vector may be advantageous in diseases with
      the risk of P. aeruginosa airway infection, such as cystic fibrosis.

PMID- 15501787
TI  - Association of iss and iucA, but not tsh, with plasmid-mediated virulence of
      avian pathogenic Escherichia coli.
AB  - Avian pathogenic Escherichia coli (APEC) is an economically important respiratory
      pathogen of chickens worldwide. Factors previously associated with the virulence
      of APEC include adhesins, iron-scavenging mechanisms, the production of colicin V
      (ColV), serum resistance, and temperature-sensitive hemagglutination, but
      virulence has generally been assessed by parenteral inoculation, which does not
      replicate the normal respiratory route of infection. A large plasmid, pVM01, is
      essential for virulence in APEC strain E3 in chickens after aerosol exposure.
      Here we establish the size of pVM01 to be approximately 160 kb and show that the
      putative virulence genes iss (increased serum survival) and tsh (temperature
      sensitive hemagglutinin) and the aerobactin operon are on the plasmid. These
      genes were not clustered on pVM01 but, rather, were each located in quite
      distinct regions. Examination of APEC strains with defined levels of respiratory
      pathogenicity after aerosol exposure showed that both the aerobactin operon and
      iss were associated with high levels of virulence in APEC but that the possession
      of either gene was sufficient for intermediate levels of virulence. In contrast,
      the presence of tsh was not necessary for high levels of virulence. Thus, both
      the aerobactin operon and iss are associated with virulence in APEC after
      exposure by the natural route of infection. The similarities between APEC and
      extraintestinal E. coli infection in other species suggests that they may be
      useful models for definition of the role of these virulence genes and of other
      novel virulence genes that may be located on their virulence plasmids.

PMID- 15501788
TI  - Tpr homologs in Treponema paraluiscuniculi Cuniculi A strain.
AB  - Treponema paraluiscuniculi, the etiologic agent of rabbit venereal syphilis, is
      morphologically indistinguishable from Treponema pallidum subsp. pallidum (T.
      pallidum), the human syphilis treponeme, and induces similar immune responses and
      histopathologic changes in the infected host. Because of their high degree of
      relatedness, comparative studies are likely to identify genetic determinants that
      contribute to pathogenesis or virulence in human syphilis. The tpr (Treponema
      pallidum repeat) genes are believed to code for potential virulence factors. In
      this study, we identified 10 tpr homologs in Treponema paraluiscuniculi Cuniculi
      A strain and determined their sequence architecture. Half of this group of
      paralogous genes were predicted to be nonfunctional due to the presence of
      frameshifts and premature stop codons. Furthermore, the immune response against
      the T. paraluiscuniculi Tpr homologs in long-term-infected rabbits was studied by
      enzyme-linked immunosorbent assay and lymphocyte proliferation assay, showing
      that TprK is the only target of the antibody and T-cell responses during
      experimental infection and emphasizing the importance of this putative virulence
      factor in venereal treponematosis.

PMID- 15501789
TI  - Effects of vlsE complementation on the infectivity of Borrelia burgdorferi
      lacking the linear plasmid lp28-1.
AB  - The loss of linear plasmid lp28-1, which contains the vls antigenic variation
      locus, is associated with reduced infectivity of Borrelia burgdorferi in
      immunocompetent mice. The recombinant shuttle vector pBBE22, which includes the
      virulence determinant BBE22 from lp25 and restores infectivity to readily
      transformable B. burgdorferi lacking lp25 and lp56, was used to determine the
      effect of trans expression of vlsE on virulence. Spirochetes lacking lp28-1 were
      complemented with the plasmid pBBE22:vlsE, containing both BBE22 and vlsE. VlsE
      protein produced by this construct was expressed and surface accessible in in
      vitro-cultured B. burgdorferi, as determined by surface proteolysis and
      immunoblot analysis. Clones lacking lp25 but containing lp28-1 and either pBBE22
      or pBBE22:vlsE were reisolated consistently from immunocompetent mice 8 weeks
      after infection. In contrast, a clone lacking both lp25 and lp28-1 and
      complemented with pBBE22:vlsE was isolated from only a single tissue of one of
      six C3H/HeN mice 8 weeks postinfection. These results indicate that either an
      intact vls antigenic variation locus or another determinant on lp28-1 is required
      to restore complete infectivity. In addition, an isogenic clone that retained
      lp28-1 was complemented with the vlsE shuttle plasmid and was examined for vlsE
      sequence variation and infectivity. Sequence variation was not observed for the
      shuttle plasmid, indicating that the cis arrangement of vlsE and the vls silent
      cassettes in lp28-1 facilitate vlsE gene conversion. Lack of vlsE sequence
      variation on the shuttle plasmid thus did not result in clearance of the trans
      complemented strain in immunocompetent mice under the conditions tested.

PMID- 15501790
TI  - Effect of dosage on immunogenicity of a Vi conjugate vaccine injected twice into
      2- to 5-year-old Vietnamese children.
AB  - In a double-blind, randomized, and placebo-controlled previous trial, the
      efficacy of Vi-rEPA for typhoid fever in 2- to 5-year-olds was 89.0% for 46
      months. Vi-rEPA contained 25 microg of Vi and induced a greater-than-eightfold
      rise in immunoglobulin G (IgG) anti-Vi in all of the vaccinees tested. In this
      investigation, we conducted a dosage-immunogenicity study of 5, 12.5, and 25
      microg of Vi-rEPA in this age group. Two doses of Vi-rEPA were injected 6 weeks
      apart. Blood samples were taken before and at 10 weeks (4 weeks after the second
      injection) and 1 year later. All postimmunization geometric mean (GM) levels were
      higher than the preimmune levels (P < 0.0001). At 10 weeks, the GM IgG anti-Vi
      level elicited by 25 microg (102 EU/ml) was higher than those elicited by 12.5
      microg (74.7 EU/ml) and 5 microg (43 EU/ml) (P < 0.004): all of the children had
      > or = 3.52 EU/ml (estimated minimum protective level). One year later, the
      levels declined about sevenfold (13.3 and 11.3 versus 6.43 EU/ml, P < 0.0001) but
      remained significantly higher than the preimmune levels (P < 0.0001), and >96% of
      the children had a greater-than-eightfold rise. This study also confirmed the
      safety and consistent immunogenicity of the four lots of Vi-rEPA used in this and
      previous trials.

PMID- 15501791
TI  - Quorum sensing: a transcriptional regulatory system involved in the pathogenicity
      of Burkholderia mallei.
AB  - Numerous gram-negative bacterial pathogens regulate virulence factor expression
      by using a cell density mechanism termed quorum sensing (QS). An in silico
      analysis of the Burkholderia mallei ATCC 23344 genome revealed that it encodes at
      least two luxI and four luxR homologues. Using mass spectrometry, we showed that
      wild-type B. mallei produces the signaling molecules N-octanoyl-homoserine
      lactone and N-decanoyl-homoserine lactone. To determine if QS is involved in the
      virulence of B. mallei, we generated mutations in each putative luxIR homologue
      and tested the pathogenicities of the derivative strains in aerosol BALB/c mouse
      and intraperitoneal hamster models. Disruption of the B. mallei QS alleles,
      especially in RJ16 (bmaII) and RJ17 (bmaI3), which are luxI mutants,
      significantly reduced virulence, as indicated by the survival of mice who were
      aerosolized with 10(4) CFU (10 50% lethal doses [LD50s]). For the B. mallei
      transcriptional regulator mutants (luxR homologues), mutation of the bmaR5 allele
      resulted in the most pronounced decrease in virulence, with 100% of the
      challenged animals surviving a dose of 10 LD50s. Using a Syrian hamster
      intraperitoneal model of infection, we determined the LD50s for wild-type B.
      mallei and each QS mutant. An increase in the relative LD50 was found for RJ16
      (bmaI1) (>967 CFU), RJ17 (bmaI3) (115 CFU), and RJ20 (bmaR5) (151 CFU) compared
      to wild-type B. mallei (<13 CFU). These findings demonstrate that B. mallei
      carries multiple luxIR homologues that either directly or indirectly regulate the
      biosynthesis of an essential virulence factor(s) that contributes to the
      pathogenicity of B. mallei in vivo.

PMID- 15501792
TI  - Distinct trafficking and localization of STEVOR proteins in three stages of the
      Plasmodium falciparum life cycle.
AB  - The genome of Plasmodium falciparum harbors three extensive multigene families,
      var, rif, and stevor (for subtelomeric variable open reading frame), located
      mainly in the subtelomeric regions of the parasite's 14 chromosomes. STEVOR
      variants are known to be expressed in asexual parasites, but no function has as
      yet been ascribed to this protein family. We have examined the expression of
      STEVOR proteins in intraerythrocytic sexual stages, gametocytes, and
      extracellular sporozoites isolated from infected Anopheles mosquitoes. In
      gametocytes, stevor transcripts appear transiently early in development but
      STEVOR proteins persist for several days and are transported out of the parasite,
      travel through the host cell cytoplasm, and localize to the erythrocyte plasma
      membrane. In contrast to asexual parasites, gametocytes move STEVOR to the
      periphery via a trafficking pathway independent of Maurer's clefts. In
      sporozoites, STEVOR appear dispersed throughout the cytoplasm in vesicle-like
      structures. The pattern of STEVOR localization we have observed in gametocytes
      and sporozoites differs significantly from that in asexual parasite stages.
      STEVOR variants are therefore likely to perform different functions in each stage
      of the parasites life cycle in which they occur.

PMID- 15501793
TI  - Prolonged toll-like receptor signaling by Mycobacterium tuberculosis and its 19
      kilodalton lipoprotein inhibits gamma interferon-induced regulation of selected
      genes in macrophages.
AB  - Infection of macrophages with Mycobacterium tuberculosis or exposure to M.
      tuberculosis 19-kDa lipoprotein for >16 h inhibits gamma interferon (IFN-gamma)
      induced major histocompatibility complex class II (MHC-II) expression by a
      mechanism involving Toll-like receptors (TLRs). M. tuberculosis was found to
      inhibit murine macrophage MHC-II antigen (Ag) processing activity induced by IFN
      gamma but not by interleukin-4 (IL-4), suggesting inhibition of IFN-gamma-induced
      gene regulation. We designed an approach to test the ability of M. tuberculosis
      infected cells to respond to IFN-gamma. To model chronic infection with M.
      tuberculosis with accompanying prolonged TLR signaling, macrophages were infected
      with M. tuberculosis or incubated with M. tuberculosis 19-kDa lipoprotein for 24
      h prior to the addition of IFN-gamma. Microarray gene expression studies were
      then used to determine whether prolonged TLR signaling by M. tuberculosis broadly
      inhibits IFN-gamma regulation of macrophage gene expression. Of 347 IFN-gamma
      induced genes, M. tuberculosis and 19-kDa lipoprotein inhibited induction of 42
      and 36%, respectively. Key genes or gene products were also examined by
      quantitative reverse transcription-PCR and flow cytometry, confirming and
      extending the results obtained by microarray studies. M. tuberculosis inhibited
      IFN-gamma induction of genes involved in MHC-II Ag processing, Ag presentation,
      and recruitment of T cells. These effects were largely dependent on myeloid
      differentiation factor 88, implying a role for TLRs. Thus, prolonged TLR
      signaling by M. tuberculosis inhibits certain macrophage responses to IFN-gamma,
      particularly those related to MHC-II Ag presentation. This inhibition may promote
      M. tuberculosis evasion of T-cell responses and persistence of infection in
      tuberculosis.

PMID- 15501794
TI  - Differences in cell activation by Chlamydophila pneumoniae and Chlamydia
      trachomatis infection in human endothelial cells.
AB  - Seroepidemiological studies and demonstration of viable bacteria in
      atherosclerotic plaques have linked Chlamydophila pneumoniae infection to the
      development of chronic vascular lesions and coronary heart disease. In this
      study, we characterized C. pneumoniae-mediated effects on human endothelial cells
      and demonstrated enhanced phosphorylation and activation of the endothelial
      mitogen-activated protein kinase (MAPK) family members extracellular receptor
      kinase (ERK1/2), p38-MAPK, and c-Jun-NH2 kinase (JNK). Subsequent interleukin-8
      (IL-8) expression was dependent on p38-MAPK and ERK1/2 activation as demonstrated
      by preincubation of endothelial cells with specific inhibitors for the p38-MAPK
      (SB202190) or ERK (U0126) pathway. Inhibition of either MAPK had almost no effect
      on intercellular cell adhesion molecule 1 (ICAM-1) expression. While Chlamydia
      trachomatis was also able to infect endothelial cells, it did not induce the
      expression of endothelial IL-8 or ICAM-1. These effects were specific for a
      direct stimulation with viable C. pneumoniae and independent of paracrine release
      of endothelial cell-derived mediators like platelet-activating factor, NO,
      prostaglandins, or leukotrienes. Thus, C. pneumoniae triggers an early signal
      transduction cascade in target cells that could lead to endothelial cell
      activation, inflammation, and thrombosis, which in turn may result in or promote
      atherosclerosis.

PMID- 15501795
TI  - The protective effect of the Mycobacterium bovis BCG vaccine is increased by
      coadministration with the Mycobacterium tuberculosis 72-kilodalton fusion
      polyprotein Mtb72F in M. tuberculosis-infected guinea pigs.
AB  - A tuberculosis vaccine candidate consisting of a 72-kDa polyprotein or fusion
      protein based upon the Mtb32 and Mtb39 antigens of Mycobacterium tuberculosis and
      designated Mtb72F was tested for its protective capacity as a potential adjunct
      to the Mycobacterium bovis BCG vaccine in the mouse and guinea pig models of this
      disease. Formulation of recombinant Mtb72F (rMtb72F) in an AS02A adjuvant
      enhanced the Th1 response to BCG in mice but did not further reduce the bacterial
      load in the lungs after aerosol challenge infection. In the more stringent guinea
      pig disease model, rMtb72F delivered by coadministration with BCG vaccination
      significantly improved the survival of these animals compared to BCG alone, with
      some animals still alive and healthy in their appearance at >100 weeks post
      aerosol challenge. A similar trend was observed with guinea pigs in which BCG
      vaccination was boosted by DNA vaccination, although this increase was not
      statistically significant due to excellent protection conferred by BCG alone.
      Histological examination of the lungs of test animals indicated that while BCG
      controls eventually died from overwhelming lung consolidation, the majority of
      guinea pigs receiving BCG mixed with rMtb72F or boosted twice with Mtb72F DNA had
      mostly clear lungs with minimal granulomatous lesions. Lesions were still
      prominent in guinea pigs receiving BCG and the Mtb72F DNA boost, but there was
      considerable evidence of lesion healing and airway remodeling and
      reestablishment. These data support the hypothesis that the coadministration or
      boosting of BCG vaccination with Mtb72F may limit the lung consolidation seen
      with BCG alone and may promote lesion resolution and healing. Collectively, these
      data suggest that enhancing BCG is a valid vaccination strategy for tuberculosis
      that is worthy of clinical evaluation.

PMID- 15501796
TI  - The hyphal and yeast forms of Candida albicans bind the complement regulator C4b
      binding protein.
AB  - Candida albicans, an important pathogenic yeast, activates all three pathways of
      the complement system. To understand how this yeast evades the effects of the
      activated system, we have analyzed the binding of the classical pathway inhibitor
      C4b-binding protein (C4BP) by C. albicans. Purified native as well as recombinant
      C4BP bound dose dependently to the yeast and hyphal forms, as shown by multiple
      methods, such as confocal microscopy, flow cytometry, a novel enzyme-linked
      immunosorbent assay, absorption from human serum, and direct binding assays with
      purified proteins. A prominent binding site was identified at the tip of the germ
      tube, a structure that is considered important for tissue penetration and
      pathogenesis. The binding site in C4BP was localized to the two N-terminal
      complement control protein domains by using recombinant deletion constructs and
      site-specific monoclonal antibodies. As the alternative pathway inhibitors factor
      H and FHL-1 also bind to C. albicans, the binding of all three plasma proteins
      was compared. Simultaneous binding of the classical regulator C4BP and the
      alternative pathway regulator factor H was demonstrated by confocal microscopy.
      In addition, FHL-1 competed for binding with C4BP, suggesting that these two
      related complement regulators bind to the same structures on the yeast surface.
      The surface-attached C4BP maintains its complement regulatory activities and
      inactivates C4b. The surface-attached human C4BP serves multiple functions
      relevant for immune evasion and likely pathogenicity. It inhibits complement
      activation at the yeast surface and, in addition, mediates adhesion of C.
      albicans to host endothelial cells.

PMID- 15501797
TI  - Mast cell-dependent control of Giardia lamblia infections in mice.
AB  - Mast cells are important for protective immunity to intestinal helminth
      infections and as mediators of allergic disease. Their role in protozoan
      infections is less well described. We have therefore analyzed mast cell responses
      and parasite control in mice infected with the protozoan Giardia lamblia. We also
      measured immunoglobulin A (IgA) responses to the parasite, as IgA can have a
      protective role in this model. c-kit w/wv mice failed to make parasite-specific
      IgA, mount a mast cell response, or eliminate the infection. Anti-c-kit-treated
      C57BL/6 mice had normal IgA responses, lacked mast cell responses, had reduced
      interleukin-6 (IL-6) mRNA in the small intestine, and failed to control the
      infection within 10 days. IL-9-deficient mice had a significant but reduced mast
      cell response and still controlled the infection within 2 weeks. Interestingly,
      IL-6-deficient mice had enhanced mast cell responses yet failed to rapidly
      control the infection. However, prevention of mast cell responses in IL-6
      deficient mice by anti-c-kit treatment did not lead to parasite elimination. Both
      IL-6- and IL-9-deficient mice had normal IgA production. IL-6-deficient mice had
      significant serum levels of mast cell mediators, histamine and mast cell protease
      1, following infection. Together, these results show that mast cells are
      important for the rapid control of Giardia infections in mice. Furthermore, they
      show that IL-6 is not necessary for these mast cell responses. Instead, they
      suggest that mast cell production of IL-6 appears to be important for control of
      this infection.

PMID- 15501799
TI  - Functional characterization of two type III secretion systems of Vibrio
      parahaemolyticus.
AB  - Vibrio parahaemolyticus, a gram-negative marine bacterium, is a worldwide cause
      of food-borne gastroenteritis. Recent genome sequencing of the clinical V.
      parahaemolyticus strain RIMD2210633 identified two sets of genes for the type III
      secretion system (TTSS), TTSS1 and TTSS2. Here, we constructed a series of mutant
      strains from RIMD2210633 to determine whether the two putative TTSS apparatus are
      functional. The cytotoxic activity of mutant strains having a deletion in one of
      the TTSS1 genes was significantly decreased compared with that of the parent and
      TTSS2-related mutant strains. In an enterotoxicity assay with the rabbit ileal
      loop test, intestinal fluid accumulation was diminished by deletion of the TTSS2
      related genes while TTSS1-related mutants caused a level of fluid accumulation
      similar to that of the parent. VopD, a protein encoded in the proximity of the
      TTSS1 region and a homologue of the Yersinia YopD, was secreted in a TTSS1
      dependent manner. In contrast, VopP, which is encoded by a pathogenicity island
      on chromosome 2 and is homologous to the Yersinia YopP, was secreted via the
      TTSS2 pathway. These results provide evidence that V. parahaemolyticus TTSSs
      function as secretion systems and may have a role in the pathogenicity of the
      organism. This is the first report of functional TTSSs in Vibrio species. The
      presence of TTSS apparatus gene homologues was demonstrated in other vibrios,
      such as Vibrio alginolyticus, Vibrio harveyi, and Vibrio tubiashii, suggesting
      that some other vibrios also contain TTSS and that the TTSS has a role in protein
      secretion in those organisms during interaction with eukaryotic cells.

PMID- 15501798
TI  - Toll-like receptor 4-dependent early elicited tumor necrosis factor alpha
      expression is critical for innate host defense against Bordetella bronchiseptica.
AB  - Toll-like receptor 4 (TLR4) mediates the response to lipopolysaccharide, and its
      activation induces the expression of a large number of inflammatory genes, many
      of which are also induced by other pathogen-associated molecular patterns.
      Interestingly, the subset of genes that are dependent on TLR4 for optimal
      expression during gram-negative bacterial infection has not been determined. We
      have previously shown that TLR4-deficient mice rapidly develop acute pneumonia
      after inoculation with Bordetella bronchiseptica, suggesting that TLR4 is
      required for expression of early elicited gene products in this model. Microarray
      analysis with macrophages derived from wild-type and TLR4-deficient mice was used
      to identify genes whose expression, within 1 h of bacterial exposure, is
      dependent on TLR4. The results of this investigation suggest that TLR4 is not
      required for the majority of the transcriptional response to B. bronchiseptica.
      However, early tumor necrosis factor alpha (TNF-alpha) mRNA expression is
      primarily dependent on TLR4 and in vitro and in vivo protein levels substantiate
      this finding. TLR4-deficient mice and TNF-alpha-/- mice are similarly susceptible
      to infection with relatively low doses of B. bronchiseptica and in vivo
      neutralization studies indicate that it is the TLR4-dependent early elicited TNF
      alpha response that is critical for preventing severe pneumonia and limiting
      bacterial growth. These results suggest that one critical role for TLR4 is the
      generation of a robust but transient TNF-alpha response that is critical to
      innate host defense during acute gram-negative respiratory infection.

PMID- 15501800
TI  - Both inducible nitric oxide synthase and NADPH oxidase contribute to the control
      of virulent phase I Coxiella burnetii infections.
AB  - Host control of Coxiella burnetii infections is believed to be mediated primarily
      by activated monocytes/macrophages. The activation of macrophages by cytokines
      leads to the production of reactive oxygen intermediates (ROI) and reactive
      nitrogen intermediates (RNI) that have potent antimicrobial activities. The
      contributions of ROI and RNI to the inhibition of C. burnetii replication were
      examined in vitro by the use of murine macrophage-like cell lines and primary
      mouse macrophages. A gamma interferon (IFN-gamma) treatment of infected cell
      lines and primary macrophages resulted in an increased production of nitric oxide
      (NO) and hydrogen peroxide (H2O2) and a significant inhibition of C. burnetii
      replication. The inhibition of replication was reversed in the murine cell line
      J774.16 upon the addition of either the inducible nitric oxide synthase (iNOS)
      inhibitor NG-monomethyl-L-arginine (NGMMLA) or the H2O2 scavenger catalase. IFN
      gamma-treated primary macrophages from iNOS-/- and p47phox-/- mice significantly
      inhibited replication but were less efficient at controlling infection than IFN
      gamma-treated wild-type macrophages. To investigate the contributions of ROI and
      RNI to resistance to infection, we performed in vivo studies, using C57BL/6 wild
      type mice and knockout mice lacking iNOS or p47phox. Both iNOS-/- and p47phox-/-
      mice were attenuated in the ability to control C. burnetii infection compared to
      wild-type mice. Together, these results strongly support a role for both RNI and
      ROI in the host control of C. burnetii infection.

PMID- 15501801
TI  - Mucosal administration of flagellin induces innate immunity in the mouse lung.
AB  - Nonsurgical intratracheal instillation of 1 microg of purified, recombinant
      flagellin in several strains of mice stimulated a transient innate immune
      response in the lung characterized by the infiltration of neutrophils and the
      rapid production of tumor necrosis factor alpha, interleukin 6, granulocyte
      colony-stimulating factor, and the chemokines keratinocyte-derived chemokine,
      MIP1alpha, and MIP-2.

PMID- 15501802
TI  - Shiga toxin binding to isolated porcine tissues and peripheral blood leukocytes.
AB  - Shiga toxin (Stx) binding sites in porcine tissues and leukocytes were identified
      by the use of Stx overlay and anti-CD77/Gb3 immunoassays. Stx1 and Stx2 bound to
      similar tissue locations and leukocytes, although some differences were noted.
      Previously unreported Stx binding sites were identified in kidney tubules,
      intestinal lymphoid aggregates, sinusoidal liver cells, alveolar macrophages, and
      peripheral blood leukocytes.

PMID- 15501803
TI  - Human factor in Staphylococcus aureus nasal carriage.
AB  - Persistent nasal carriers and noncarriers of Staphylococcus aureus were
      inoculated with a mixture of different S. aureus strains. The majority of
      noncarriers and nearly all persistent carriers returned to their original carrier
      state after artificial inoculation. Furthermore, the majority of persistent
      carriers tested positive again for their original resident strain. Using a human
      nasal inoculation model, we here demonstrate that the human factor is an
      important determinant of S. aureus nasal carriage.

PMID- 15501805
TI  - Streptococcus pneumoniae-induced inhibition of rat ependymal cilia is attenuated
      by antipneumolysin antibody.
AB  - Ciliated ependymal cells line the ventricular surfaces and aqueducts of the
      brain. In ex vivo experiments, pneumolysin caused rapid inhibition of the
      ependymal ciliary beat frequency and caused ependymal cell disruption. Wild-type
      pneumococci and pneumococci deficient in pneumolysin caused ciliary slowing, but
      penicillin lysis of wild-type, not pneumolysin-deficient, pneumococci increased
      the extent of ciliary inhibition. This effect was abolished by antipneumolysin
      antibody. Ependymal ciliary stasis by purified pneumolysin was also blocked by
      the addition of antipneumolysin monoclonal antibodies. These data show that
      antibiotic lysis of Streptococcus pneumoniae can be detrimental to the ciliated
      ependyma and that antipneumolysin antibody may have a therapeutic potential.

PMID- 15501804
TI  - Moraxella catarrhalis coaggregates with Streptococcus pyogenes and modulates
      interactions of S. pyogenes with human epithelial cells.
AB  - The pathogens Streptococcus pyogenes and Moraxella catarrhalis colonize
      overlapping regions of the human nasopharynx. We have found that M. catarrhalis
      can dramatically increase S. pyogenes adherence to human epithelial cells and
      that species-specific coaggregation of these bacteria correlates with this
      enhanced adherence.

PMID- 15501806
TI  - Cleavage of the N-linked oligosaccharide from the surfaces of Chlamydia species
      affects attachment and infectivity of the organisms in human epithelial and
      endothelial cells.
AB  - Previous studies demonstrated that the high-mannose oligosaccharide N linked to
      the Chlamydia major outer membrane protein inhibited the attachment and
      infectivity of the organism. The present study showed that cleavage of the glycan
      with N-glycanase decreased the attachment and infectivity of chlamydial organisms
      in human epithelial and endothelial cells.

PMID- 15501807
TI  - Variations in Barbour-Stoenner-Kelly culture medium modulate infectivity and
      pathogenicity of Borrelia burgdorferi clinical isolates.
AB  - The effects of variations in Barbour-Stoenner-Kelly (BSK) medium on the
      infectivity and pathogenicity of Borrelia burgdorferi clinical isolates were
      assessed by retrospective and prospective studies using a murine model of Lyme
      borreliosis. Thirty of 35 (86%) mice infected with any of six virulent B.
      burgdorferi clinical isolates grown in a BSK-H medium developed clinically
      apparent arthritis. By contrast, arthritis was observed in only 25 of 60 (42%)
      mice inoculated with two of these B. burgdorferi strains grown in a different lot
      of BSK-H medium (P < 0.001). In a prospective study, mice inoculated with a B.
      burgdorferi clinical isolate grown in a BSK medium prepared in-house produced
      significantly greater disease than those injected with the same isolate cultured
      in BSK-H medium (P < 0.05). The attenuated pathogenicity is not due to the loss
      of plasmids during in vitro cultivation. The data suggest that variations in BSK
      medium have a significant impact on the infectivity and pathogenicity of B.
      burgdorferi clinical isolates.

PMID- 15501808
TI  - LcrV synthesis is altered by DNA adenine methylase overproduction in Yersinia
      pseudotuberculosis and is required to confer immunity in vaccinated hosts.
AB  - Yersinia pseudotuberculosis mutants that overproduce the DNA adenine methylase
      (DamOP Yersinia) are attenuated, confer robust protective immune responses, and
      synthesize or secrete several Yersinia outer proteins (Yops) under conditions
      that are nonpermissive for synthesis and secretion in wild-type strains. To
      understand the molecular basis of immunity elicited by DamOP Yersinia, we
      investigated the effects of Dam overproduction on the synthesis and localization
      of a principal Yersinia immunogen, LcrV, a low-calcium-responsive virulence
      factor involved in Yop synthesis, localization, and suppression of host
      inflammatory activities. Dam overproduction relaxed the stringent temperature and
      calcium regulation of LcrV synthesis. Moreover, the LcrV-dependent synthesis and
      localization of the actin cytotoxin, YopE, were shown to be relaxed in DamOP
      cells, suggesting that the synthesis and localization of Yops can occur via both
      LcrV-dependent and -independent mechanisms. Last, the immunity conferred by DamOP
      Yersinia was strictly dependent on the presence of LcrV, which may result from
      its role (i) as an immunogen, (ii) as an immunomodulator of host anti
      inflammatory activities, or (iii) in the altered synthesis and localization of
      Yops that could contribute to immunogen repertoire expansion.

PMID- 15501809
TI  - Identification of genes transcribed by Actinobacillus pleuropneumoniae in
      necrotic porcine lung tissue by using selective capture of transcribed sequences.
AB  - Genes expressed by Actinobacillus pleuropneumoniae in necrotic porcine lung
      tissue were identified by selective capture of transcribed sequences analysis. In
      total, 46 genes were identified, 20 of which have been previously reported to be
      associated with in vivo expression or virulence in A. pleuropneumoniae or in
      other organisms.

PMID- 15501810
TI  - Human galectin-3 promotes Trypanosoma cruzi adhesion to human coronary artery
      smooth muscle cells.
AB  - Human galectin-3 binds to the surface of Trypanosoma cruzi trypomastigotes and
      human coronary artery smooth muscle (CASM) cells. CASM cells express galectin-3
      on their surface and secrete it. Exogenous galectin-3 increased the binding of T.
      cruzi to CASM cells. Trypanosome binding to CASM cells was enhanced when either
      T. cruzi or CASM cells were preincubated with galectin-3. Cells stably
      transfected with galectin-3 antisense show a dramatic decrease in galectin-3
      expression and very little T. cruzi adhesion to cells. The addition of galectin-3
      to these cells restores their initial capacity to bind to trypanosomes. Thus,
      host galectin-3 expression is required for T. cruzi adhesion to human cells and
      exogenous galectin-3 enhances this process, leading to parasite entry.

PMID- 15501811
TI  - Comparative analysis of locus of enterocyte effacement pathogenicity islands of
      atypical enteropathogenic Escherichia coli.
AB  - The pathogenicity of enteropathogenic Escherichia coli (EPEC) is linked to the
      locus of enterocyte effacement, or LEE, encoding a type III secretion system
      (T3SS) that directly transfers bacterial effector proteins into eukaryotic cells.
      Atypical diffusely adhering EPEC (DA-EPEC) strains that harbor homologues of the
      LEE but lack the EPEC adherence factor plasmid have been increasingly associated
      with outbreaks of diarrhea. In this study, we have completely sequenced and
      functionally characterized LEE pathogenicity islands derived from the clinical DA
      EPEC isolates 3431 (O8:H-) and 0181 (O119:H9:K61). LEE3431 and LEE0181 exhibit
      genetic organization analogous to that of the prototype LEE(E2348/69). Genes
      constituting the T3SS apparatus are highly conserved. However, LEE-encoded
      effector proteins exhibit major differences. Transfer and functional expression
      of LEE0181 in an E. coli XL1 blue MR background demonstrated that LEE0181
      contains all the information for signal transduction and pedestal formation.

PMID- 15501812
TI  - Interleukin-15-deficient mice develop protective immunity to Toxoplasma gondii.
AB  - Previous studies have suggested an important role for interleukin-15 (IL-15) in
      resistance to and memory for Toxoplasma gondii infection. The studies presented
      here reveal that IL-15 is not required for infection-induced expansion of NK or
      CD8+ T cells. Furthermore, IL-15-/- mice develop long-term protective immunity to
      this pathogen.

PMID- 15501813
TI  - In vitro and in vivo evaluation of staphylococcal superantigen peptide
      antagonists.
AB  - Superantigen peptide antagonists failed to block T-cell activation and cytokine
      production as well as toxic shock induced by staphylococcal enterotoxin B (SEB)
      in HLA class II transgenic mice. They also failed to inhibit the binding of SEB
      to HLA class II molecules as well as activation of human T lymphocytes in vitro.

PMID- 15501814
TI  - Lack of stage-specific proteins in coccoid Helicobacter pylori cells.
AB  - Helicobacter pylori exists in two distinct forms, rod shaped or coccoid, in
      stomachs of infected patients. Based on in vitro proteome comparisons, there are
      no detectable coccoid-specific proteins, which argues against the specific
      adaptation of coccoid Helicobacter to distinct biological functions, such as
      enhanced persistence or transmission to other hosts.

PMID- 15501815
TI  - Identification of Neisseria meningitidis genetic loci involved in the modulation
      of phase variation frequencies.
AB  - It has been proposed that increased phase variation frequencies in Neisseria
      meningitidis augment transmissibility and invasiveness. A Himar1 mariner
      transposon mutant library was constructed in serogroup A N. meningitidis and
      screened for clones with increased phase variation frequencies. Insertions
      increasing the frequency of slippage events within mononucleotide repeat tracts
      were identified in three known phase variation-modulating genes (mutS, mutL, and
      uvrD), as well as six additional loci (pilP, fbpA, fbpB, NMA1233, and two
      intergenic regions). The implications of these insertion mutations are discussed.

PMID- 15501816
TI  - Streptococcus mutans surface alpha-enolase binds salivary mucin MG2 and human
      plasminogen.
AB  - Matrix-assisted laser desorption ionization-time of flight mass spectrometry
      analysis identified enolase as a cell surface component of Streptococcus mutans,
      which was confirmed by enzyme-linked immunosorbent assay, Western blotting, and
      transmission electron microscopy. Surface enolase was demonstrated to bind to
      human plasminogen and salivary mucin MG2. The results suggested a role for
      enolase in S. mutans attachment, clearance, or breach of the bloodstream barrier.

PMID- 15501817
TI  - Interactor-mediated nuclear translocation and retention of protein phosphatase-1.
AB  - Protein Ser/Thr phosphatase-1 (PP1) is a ubiquitous eukaryotic enzyme that
      controls numerous cellular processes by the dephosphorylation of key regulatory
      proteins. PP1 is expressed in various cellular compartments but is most abundant
      in the nucleus. We have examined the determinants for the nuclear localization of
      enhanced green fluorescent protein-tagged PP1 in COS1 cells. Our studies show
      that PP1gamma(1) does not contain a functional nuclear localization signal and
      that its nuclear accumulation does not require Sds22, which has previously been
      implicated in the nuclear accumulation of PP1 in yeast (Peggie, M. W., MacKelvie,
      S. H., Bloecher, A., Knatko, E. V., Tatchell, K., and Stark, M. J. R. (2002) J.
      Cell Sci. 115, 195-206). However, the nuclear targeting of PP1 isoforms was
      alleviated by the mutation of their binding sites for proteins that interact via
      an RVXF motif. Moreover, one of the mutants with a cytoplasmic accumulation and
      decreased affinity for RVXF motifs (PP1gamma(1)-F257A) could be re-targeted to
      the nucleus by the overexpression of nuclear interactors (NIPP1 (nuclear
      inhibitor of PP1) and PNUTS (PP1 nuclear targeting subunit)) with a functional
      RVXF motif. Also, the addition of a synthetic RVXF-containing peptide to
      permeabilized cells resulted in the loss of nuclear enhanced green fluorescent
      protein-PP1gamma(1). Finally, NIPP1(-/-) mouse embryos showed a nuclear
      hyperphosphorylation on threonine, consistent with a role for NIPP1 in the
      nuclear targeting and/or retention of PP1. Our data suggest that both the nuclear
      translocation and the nuclear retention of PP1 depend on its binding to
      interactors with an RVXF motif.

PMID- 15501818
TI  - Crystal structure of the human cytosolic sialidase Neu2. Evidence for the dynamic
      nature of substrate recognition.
AB  - Gangliosides play key roles in cell differentiation, cell-cell interactions, and
      transmembrane signaling. Sialidases hydrolyze sialic acids to produce asialo
      compounds, which is the first step of degradation processes of glycoproteins and
      gangliosides. Sialidase involvement has been implicated in some lysosomal storage
      disorders such as sialidosis and galactosialidosis. Neu2 is a recently identified
      human cytosolic sialidase. Here we report the first high resolution x-ray
      structures of mammalian sialidase, human Neu2, in its apo form and in complex
      with an inhibitor, 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (DANA). The
      structure shows the canonical six-blade beta-propeller observed in viral and
      bacterial sialidases with its active site in a shallow crevice. In the complex
      structure, the inhibitor lies in the catalytic crevice surrounded by ten amino
      acids. In particular, the arginine triad, conserved among sialidases, aids in the
      proper positioning of the carboxylate group of DANA within the active site
      region. The tyrosine residue, Tyr(334), conserved among mammalian and bacterial
      sialidases as well as in viral neuraminidases, facilitates the enzymatic reaction
      by stabilizing a putative carbonium ion in the transition state. The loops
      containing Glu(111) and the catalytic aspartate Asp(46) are disordered in the apo
      form but upon binding of DANA become ordered to adopt two short alpha-helices to
      cover the inhibitor, illustrating the dynamic nature of substrate recognition.
      The N-acetyl and glycerol moieties of DANA are recognized by Neu2 residues not
      shared by bacterial sialidases and viral neuraminidases, which can be regarded as
      a key structural difference for potential drug design against bacteria,
      influenza, and other viruses.

PMID- 15501819
TI  - The role of an activating peptide in protease-mediated suicide of Escherichia
      coli K12.
AB  - Activation of latent proteinases ensures that the timing of proteolysis is
      regulated precisely, a process that generally involves proteolytic excision of a
      pro-region or a tightly bound inhibitor. Here we define the activation mechanism
      for Lit, a dormant suicide proteinase in Escherichia coli K-12. Previous work has
      shown that Gol, a short sequence within the major capsid protein gp23, activates
      Lit during the latter stages of T4 phage infection. This results in cell death
      and exclusion of the phage from the culture. The Lit site specifically cleaves
      the host translation factor EF-Tu (elongation factor Tu) after it has formed a
      weak complex with Gol, which can be supplied as a 29-residue peptide. Gol is
      absolutely required for Lit activation. but its role in proteolysis is unknown.
      Using a purified three-component system and kinetic analysis, we demonstrate that
      under physiological conditions Lit hydrolyzes its substrate very slowly (k(cat)
      of approximately 1 s(-1)). Given the abundance of EF-Tu in the cell, this finding
      is consistent with a cell-killing mechanism in which a few cleaved EF-Tu proteins
      are able block translating ribosomes from functioning. We also demonstrate that
      less than half of the 29 Gol residues are needed for Lit activation and that the
      role of the peptide is not to provide catalytic groups but to influence catalysis
      indirectly through stabilization of the ternary Lit.Gol.EF-Tu complex. Hence,
      phage-elicited suicide of E. coli K-12 by Lit is a variant form of "cofactor
      induced activation," a mechanism of protease activation that has only been
      documented previously in pathogen subversion of mammalian hemostasis cascades.

PMID- 15501820
TI  - Signal-anchored proteins follow a unique insertion pathway into the outer
      membrane of mitochondria.
AB  - Signal-anchored proteins are a class of mitochondrial outer membrane proteins
      that expose a hydrophilic domain to the cytosol and are anchored to the membrane
      by a single transmembrane domain in the N-terminal region. Like the vast majority
      of mitochondrial proteins, signal-anchored proteins are synthesized on cytosolic
      ribosomes and are subsequently imported into the organelle. We have studied the
      mechanisms by which precursors of these proteins are recognized by the
      mitochondria and are inserted into the outer membrane. The import of signal
      anchored proteins was found to be independent of the known import receptors,
      Tom20 and Tom70, but to require the major Tom component, Tom40. In contrast to
      precursors destined to internal compartments of mitochondria and those of outer
      membrane beta-barrel proteins, precursors of signal-anchored proteins appear not
      to be inserted via the general import pore. Taken together, we propose a novel
      pathway for insertion of these proteins into the outer membrane of mitochondria.

PMID- 15501821
TI  - Crystal structure of human maspin, a serpin with antitumor properties: reactive
      center loop of maspin is exposed but constrained.
AB  - Maspin, a member of the serpin superfamily, has tumor suppressing activity
      against breast and prostate cancer. Maspin inhibits tumor growth by blocking cell
      invasion, and its reactive center loop (RCL) is thought to mediate this activity.
      To understand this function on the molecular level, we have solved the three
      dimensional structure of Maspin to 3.1 A resolution. The molecular structure
      shows the characteristic features of the serpin fold, but the RCL of Maspin is
      unique in length, composition, and placement. Although the RCL of Maspin is
      accessible and cleavable by some proteinases, it functions in the uncleaved,
      constrained conformation observed here. These structural results will contribute
      to our understanding of the mechanism by which Maspin suppresses tumors.

PMID- 15501822
TI  - Activation-dependent conformational changes in {beta}-arrestin 2.
AB  - Beta-arrestins are multifunctional adaptor proteins, which mediate
      desensitization, endocytosis, and alternate signaling pathways of seven membrane
      spanning receptors (7MSRs). Crystal structures of the basal inactive state of
      visual arrestin (arrestin 1) and beta-arrestin 1 (arrestin 2) have been resolved.
      However, little is known about the conformational changes that occur in beta
      arrestins upon binding to the activated phosphorylated receptor. Here we
      characterize the conformational changes in beta-arrestin 2 (arrestin 3) by
      comparing the limited tryptic proteolysis patterns and matrix-assisted laser
      desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) profiles of
      beta-arrestin 2 in the presence of a phosphopeptide (V(2)R-pp) derived from the C
      terminus of the vasopressin type II receptor (V(2)R) or the corresponding
      nonphosphopeptide (V(2)R-np). V(2)R-pp binds to beta-arrestin 2 specifically,
      whereas V(2)R-np does not. Activation of beta-arrestin 2 upon V(2)R-pp binding
      involves the release of its C terminus, as indicated by exposure of a previously
      inaccessible cleavage site, one of the polar core residues Arg(394), and
      rearrangement of its N terminus, as indicated by the shielding of a previously
      accessible cleavage site, residue Arg(8). Interestingly, binding of the polyanion
      heparin also leads to release of the C terminus of beta-arrestin 2; however,
      heparin and V(2)R-pp have different binding site(s) and/or induce different
      conformational changes in beta-arrestin 2. Release of the C terminus from the
      rest of beta-arrestin 2 has functional consequences in that it increases the
      accessibility of a clathrin binding site (previously demonstrated to lie between
      residues 371 and 379) thereby enhancing clathrin binding to beta-arrestin 2 by 10
      fold. Thus, the V(2)R-pp can activate beta-arrestin 2 in vitro, most likely
      mimicking the effects of an activated phosphorylated 7MSR. These results provide
      the first direct evidence of conformational changes associated with the
      transition of beta-arrestin 2 from its basal inactive conformation to its
      biologically active conformation and establish a system in which receptor-beta
      arrestin interactions can be modeled in vitro.

PMID- 15501824
TI  - In vitro refolding/unfolding pathways of amphioxus insulin-like peptide:
      implications for folding behavior of insulin family proteins.
AB  - Amphioxus insulin-like peptide (AILP) belongs to the insulin superfamily and is
      proposed as the common ancestor of insulin and insulin-like growth factor 1.
      Herein, the studies on oxidative refolding and reductive unfolding of AILP are
      reported. During the refolding process, four major intermediates, P1, P2, P3, and
      P4, were captured, which were almost identical to those intermediates, U1, U2,
      U3, and U4, captured during the AILP unfolding process. P4 (U4) has the native
      disulfide A20-B19; P1 (U1), P2 (U2), and P3 (U3) have two disulfide bonds, which
      include A20-B19. Based on the analysis of the time course distribution and
      properties of the intermediates, we proposed that fully reduced AILP refolded
      through 1SS, 2SS, and 3SS intermediate stages to the native form; native AILP
      unfolded through 2SS and 1SS intermediate stages to the full reduced form. A
      schematic flow chart of major oxidative refolding and reductive unfolding
      pathways of AILP was proposed. Implication for the folding behavior of insulin
      family proteins was discussed. There may be seen three common folding features in
      the insulin superfamily: 1) A20-B19 disulfide is most important and formed during
      the initial stage of folding process; 2) the second disulfide is nonspecifically
      formed, which then rearranged to native disulfide; 3) in vitro refolding and
      unfolding pathways may share some common folding intermediates but flow in
      opposite directions. Furthermore, although swap AILP is a thermodynamically
      stable final product, a refolding study of swap AILP demonstrated that it is also
      a productive intermediate of native AILP during refolding.

PMID- 15501823
TI  - C2-alpha-lactylthiamin diphosphate is an intermediate on the pathway of thiamin
      diphosphate-dependent pyruvate decarboxylation. Evidence on enzymes and models.
AB  - Thiamin diphosphate (ThDP)-dependent decarboxylations are usually assumed to
      proceed by a series of covalent intermediates, the first one being the C2
      trimethylthiazolium adduct with pyruvate, C2-alpha-lactylthiamin diphosphate
      (LThDP). Herein is addressed whether such an intermediate is kinetically
      competent with the enzymatic turnover numbers. In model studies it is shown that
      the first-order rate constant for decarboxylation can indeed exceed 50 s(-1) in
      tetrahydrofuran as solvent, approximately 10(3) times faster than achieved in
      previous model systems. When racemic LThDP was exposed to the E91D yeast pyruvate
      decarboxylase variant, or to the E1 subunit of the pyruvate dehydrogenase complex
      (PDHc-E1) from Escherichia coli, it was partitioned between reversion to pyruvate
      and decarboxylation. Under steady-state conditions, the rate of these reactions
      is severely limited by the release of ThDP from the enzyme. Under pre-steady
      state conditions, the rate constant for decarboxylation on exposure of LThDP to
      the E1 subunit of the pyruvate dehydrogenase complex was 0.4 s(-1), still more
      than a 100-fold slower than the turnover number. Because these experiments
      include binding, decarboxylation, and oxidation (for detection purposes), this is
      a lower limit on the rate constant for decarboxylation. The reasons for this slow
      reaction most likely include a slow conformational change of the free LThDP to
      the V conformation enforced by the enzyme. Between the results from model studies
      and those from the two enzymes, it is proposed that LThDP is indeed on the
      decarboxylation pathway of the two enzymes studied, and once LThDP is bound the
      protein needs to provide little assistance other than a low polarity environment.

PMID- 15501825
TI  - Second-site suppression of a nonfunctional mutation within the Leishmania
      donovani inosine-guanosine transporter.
AB  - LdNT2 is a member of the equilibrative nucleoside transporter family, which
      possesses several conserved residues located mainly within transmembrane domains.
      One of these residues, Asp(389) within LdNT2, was shown previously to be critical
      for transporter function without affecting ligand affinity or plasma membrane
      targeting. To further delineate the role of Asp(389) in LdNT2 function, second
      site suppressors of the ldnt2-D389N null mutation were selected in yeast
      deficient in purine nucleoside transport and incapable of purine biosynthesis. A
      library of random mutants within the ldnt2-D389N background was screened in yeast
      for restoration of growth on inosine. Twelve different clones were obtained, each
      containing secondary mutations enabling inosine transport. One mutation, N175I,
      occurred in four clones and conferred augmented inosine transport capability
      compared with LdNT2 in yeast. N175I was subsequently introduced into an ldnt2
      D389N construct tagged with green fluorescent protein and transfected into a
      Deltaldnt1/Deltaldnt2 Leishmania donovani knockout. GFP-N175I/D389N significantly
      suppressed the D389N phenotype and targeted properly to the plasma membrane and
      flagellum. Most interestingly, N175I increased the inosine K(m) by 10-fold within
      the D389N background relative to wild type GFP-LdNT2. Additional substitutions
      introduced at Asn(175) established that only large, nonpolar amino acids
      suppressed the D389N phenotype, indicating that suppression by Asn(175) has a
      specific size and charge requirement. Because multiple suppressor mutations
      alleviate the constraint imparted by the D389N mutation, these data suggest that
      Asp(389) is a conformationally sensitive residue. To impart spatial information
      to the clustering of second-site mutations, a three-dimensional model was
      constructed based upon members of the major facilitator superfamily using
      threading analysis. The model indicates that Asn(175) and Asp(389) lie in close
      proximity and that the second-site suppressor mutations cluster to one region of
      the transporter.

PMID- 15501826
TI  - Histone H2A and Spt10 cooperate to regulate induction and autoregulation of the
      CUP1 metallothionein.
AB  - Copper is an essential cellular cofactor that becomes toxic at high levels.
      Copper homeostasis is tightly regulated by opposing mechanisms that control
      copper import, export, and copper binding capacity within the cell. High levels
      of copper induce the expression of metallothioneins, small sulfhydryl-rich
      proteins with high metal binding capabilities that serve as neutralizers of toxic
      levels of metals. In yeast, the CUP1 gene encodes a copper metallothionein that
      is strongly induced in response to metals and other stress and is subsequently
      rapidly down-regulated. Activation of CUP1 is mediated by the copper-responsive
      transcriptional activator AceI, and also requires the histone acetylase Spt10 for
      full induction. We have examined the role of histone H2A in the normal regulation
      of the CUP1 gene. We have shown that specific H2A mutations in combination with
      spt10 deletions result in aberrant regulation of CUP1 expression. Certain lysine
      mutations in H2A alleviate the transcriptional defect in spt10 Delta strains,
      though CUP1 activation is still delayed in these mutants; however, CUP1 shutdown
      is normal. In contrast, serine mutations in H2A prevent CUP1 shutdown when
      combined with spt10 deletions. In addition, swi/snf mutants exhibit both impaired
      CUP1 induction and failure to shut down CUP1 normally. Finally, different Spt10
      dependent histone acetylation events correlate with induction and shutdown. Taken
      together, these data indicate that CUP1 transcriptional shutdown, like induction,
      is an active process controlled by the chromatin structure of the gene. These
      results provide new insights for the role of chromatin structure in metal
      homeostasis.

PMID- 15501827
TI  - Conformational changes in BID, a pro-apoptotic BCL-2 family member, upon membrane
      binding. A site-directed spin labeling study.
AB  - The BCL-2 family proteins constitute a critical control point in apoptosis. BCL-2
      family proteins display structural homology to channel-forming bacterial toxins,
      such as colicins, transmembrane domain of diphtheria toxin, and the N-terminal
      domain of delta-endotoxin. By analogy, it has been hypothesized the BCL-2 family
      proteins would unfold and insert into the lipid bilayer upon membrane
      association. We applied the site-directed spin labeling method of electron
      paramagnetic resonance spectroscopy to the pro-apoptotic member BID. Here we show
      that helices 6-8 maintain an alpha-helical conformation in membranes with a lipid
      composition resembling mitochondrial outer membrane contact sites. However,
      unlike colicins and the transmembrane domain of diphtheria toxin, these helices
      of BID are bound to the lipid bilayer without adopting a transmembrane
      orientation. Our study presents a more detailed model for the reorganization of
      the structure of tBID on membranes.

PMID- 15501828
TI  - A crucial role for exopolysaccharide modification in bacterial biofilm formation,
      immune evasion, and virulence.
AB  - Biofilms play an important role in many chronic bacterial infections. Production
      of an extracellular mixture of sugar polymers called exopolysaccharide is
      characteristic and critical for biofilm formation. However, there is limited
      information about the mechanisms involved in the biosynthesis and modification of
      exopolysaccharide components and how these processes influence bacterial
      pathogenesis. Staphylococcus epidermidis is an important human pathogen that
      frequently causes persistent infections by biofilm formation on indwelling
      medical devices. It produces a poly-N-acetylglucosamine molecule that emerges as
      an exopolysaccharide component of many bacterial pathogens. Using a novel method
      based on size exclusion chromatography-mass spectrometry, we demonstrate that the
      surface-attached protein IcaB is responsible for deacetylation of the poly-N
      acetylglucosamine molecule. Most likely due to the loss of its cationic
      character, non-deacetylated poly-acetylglucosamine in an isogenic icaB mutant
      strain was devoid of the ability to attach to the bacterial cell surface.
      Importantly, deacetylation of the polymer was essential for key virulence
      mechanisms of S. epidermidis, namely biofilm formation, colonization, and
      resistance to neutrophil phagocytosis and human antibacterial peptides.
      Furthermore, persistence of the icaB mutant strain was significantly impaired in
      a murine model of device-related infection. This is the first study to describe a
      mechanism of exopolysaccharide modification that is indispensable for the
      development of biofilm-associated human disease. Notably, this general virulence
      mechanism is likely similar for other pathogenic bacteria and constitutes an
      excellent target for therapeutic maneuvers aimed at combating biofilm-associated
      infection.

PMID- 15501829
TI  - Mechanistic and structural analysis of a family 31 alpha-glycosidase and its
      glycosyl-enzyme intermediate.
AB  - We have determined the first structure of a family 31 alpha-glycosidase, that of
      YicI from Escherichia coli, both free and trapped as a 5-fluoroxylopyranosyl
      enzyme intermediate via reaction with 5-fluoro-alpha-D-xylopyranosyl fluoride.
      Our 2.2-A resolution structure shows an intimately associated hexamer with
      structural elements from several monomers converging at each of the six active
      sites. Our kinetic and mass spectrometry analyses verified several of the
      features observed in our structural data, including a covalent linkage from the
      carboxylate side chain of the identified nucleophile Asp(416) to C-1 of the sugar
      ring. Structure-based sequence comparison of YicI with the mammalian alpha
      glucosidases lysosomal alpha-glucosidase and sucrase-isomaltase predicts a high
      level of structural similarity and provides a foundation for understanding the
      various mutations of these enzymes that elicit human disease.

PMID- 15501830
TI  - Family 6 carbohydrate binding modules recognize the non-reducing end of beta-1,3
      linked glucans by presenting a unique ligand binding surface.
AB  - Enzymes that hydrolyze insoluble complex polysaccharide structures contain non
      catalytic carbohydrate binding modules (CBMS) that play a pivotal role in the
      action of these enzymes against recalcitrant substrates. Family 6 CBMs (CBM6s)
      are distinct from other CBM families in that these protein modules contain
      multiple distinct ligand binding sites, a feature that makes CBM6s particularly
      appropriate receptors for the beta-1,3-glucan laminarin, which displays an
      extended U-shaped conformation. To investigate the mechanism by which family 6
      CBMs recognize laminarin, we report the biochemical and structural properties of
      a CBM6 (designated BhCBM6) that is located in an enzyme, which is shown, in this
      work, to display beta-1,3-glucanase activity. BhCBM6 binds beta-1,3
      glucooligosaccharides with affinities of approximately 1 x 10(5) m(-1). The x-ray
      crystal structure of this CBM in complex with laminarihexaose reveals similarity
      with the structures of other CBM6s but a unique binding mode. The binding cleft
      in this protein is sealed at one end, which prevents binding of linear
      polysaccharides such as cellulose, and the orientation of the sugar at this site
      prevents glycone extension of the ligand and thus conferring specificity for the
      non-reducing ends of glycans. The high affinity for extended beta-1,3
      glucooligosaccharides is conferred by interactions with the surface of the
      protein located between the two binding sites common to CBM6s and thus reveals a
      third ligand binding site in family 6 CBMs. This study therefore demonstrates how
      the multiple binding clefts and highly unusual protein surface of family 6 CBMs
      confers the extensive range of specificities displayed by this protein family.
      This is in sharp contrast to other families of CBMs where variation in
      specificity between different members reflects differences in the topology of a
      single binding site.

PMID- 15501832
TI  - Do we still need care homes?

PMID- 15501831
TI  - Mitochondrial proteomic analysis of a cell line model of familial amyotrophic
      lateral sclerosis.
AB  - Mutations in copper-zinc superoxide dismutase (SOD1) have been linked to a subset
      of familial amytrophic lateral sclerosis (fALS), a fatal neurodegenerative
      disease characterized by progressive motor neuron death. An increasing amount of
      evidence supports that mitochondrial dysfunction and apoptosis activation play a
      critical role in the fALS etiology, but little is known about the mechanisms by
      which SOD1 mutants cause the mitochondrial dysfunction and apoptosis. In this
      study, we use proteomic approaches to identify the mitochondrial proteins that
      are altered in the presence of a fALS-causing mutant G93A-SOD1. A comprehensive
      characterization of mitochondrial proteins from NSC34 cells, a motor neuron-like
      cell line, was achieved by two independent proteomic approaches. Four hundred
      seventy unique proteins were identified in the mitochondrial fraction
      collectively, 75 of which are newly discovered proteins that previously had only
      been reported at the cDNA level. Two-dimensional gel electrophoresis was
      subsequently used to analyze the differences between the mitochondrial proteomes
      of NSC34 cells expressing wild-type and G93A-SOD1. Nine and 36 protein spots
      displayed elevated and suppressed abundance respectively in G93A-SOD1-expressing
      cells. The 45 spots were identified by MS, and they include proteins involved in
      mitochondrial membrane transport, apoptosis, the respiratory chain, and molecular
      chaperones. In particular, alterations in the post-translational modifications of
      voltage-dependent anion channel 2 (VDAC2) were found, and its relevance to
      regulating mitochondrial membrane permeability and activation of apoptotic
      pathways is discussed. The potential role of other proteins in the mutant SOD1
      mediated fALS is also discussed. This study has produced a short list of
      mitochondrial proteins that may hold the key to the mechanisms by which SOD1
      mutants cause mitochondrial dysfunction and neuronal death. It has laid the
      foundation for further detailed functional studies to elucidate the role of
      particular mitochondrial proteins, such as VDAC2, in the pathogenesis of familial
      ALS.

PMID- 15501833
TI  - Inappropriate prescribing in older people.

PMID- 15501834
TI  - Preventing falls and injuries in care homes.

PMID- 15501835
TI  - Between the Devil and the Deep Blue Sea--balancing the risks and potential
      benefits of warfarin for older people with atrial fibrillation.

PMID- 15501836
TI  - Vitamin D supplementation improves neuromuscular function in older people who
      fall.
AB  - BACKGROUND: vitamin D supplementation reduces the incidence of fractures in older
      adults. This may be partly mediated by effects of vitamin D on neuromuscular
      function. OBJECTIVE: to determine the effects of vitamin D supplementation on
      aspects of neuromuscular function known to be risk factors for falls and
      fractures. DESIGN: randomised, double-blind, placebo-controlled study. SETTING:
      falls clinic taking referrals from general practitioners and accident and
      emergency department. SUBJECTS: 139 ambulatory subjects (>/=65 years) with a
      history of falls and 25-hydroxyvitamin D (25OHD) </=12 microg/l. INTERVENTION:
      patients were randomised to receive a single intramuscular injection of 600,000
      i.u. ergocalciferol or placebo. OUTCOME MEASURES: assessments including
      biochemistry, postural sway, choice reaction time (CRT), aggregate functional
      performance time (AFPT), and quadriceps strength were carried out at baseline and
      6 months post-intervention. RESULTS: baseline characteristics were comparable
      between both groups. 25OHD in the treatment group increased significantly at 6
      months. AFPT deteriorated in the control group and improved in the intervention
      group, representing a significant difference between groups (+6.6 s versus -2.0
      s, t = 2.80, P < 0.05). Similar changes were observed for CRT (-0.06 s versus
      +0.41 s, t = -2.52, P < 0.01) and postural sway (+0.0025 versus -0.0138, t =
      2.35, P < 0.02). There was no significant difference in muscle strength change
      between groups (-10 N versus -2 N, t = -1.26, ns). A significant correlation
      between change in AFPT and change in 25OHD levels was observed (r = 0.19, P =
      0.03). There was no significant difference in the number of falls (0.39 versus
      0.24, t = 1.08, P = 0.28) or fallers (14 versus 11, P = 0.52) between two groups.
      CONCLUSIONS: vitamin D supplementation, in fallers with vitamin D insufficiency,
      has a significant beneficial effect on functional performance, reaction time and
      balance, but not muscle strength. This suggests that vitamin D supplementation
      improves neuromuscular or neuroprotective function, which may in part explain the
      mechanism whereby vitamin D reduces falls and fractures.

PMID- 15501837
TI  - Postural stability in the elderly: a comparison between fallers and non-fallers.
AB  - BACKGROUND: the identification of specific risk factors for falls in community
      dwelling elderly persons is required to identify older people at risk of falling.
      OBJECTIVE: the aim of the study was to determine the ability of various
      biomechanical measures of postural stability to identify fallers in the elderly
      population. METHOD: 19 subjects (78.4 +/- 1.3 years old) who reported having
      fallen unexpectedly at least twice in the last 6 months, and 124 non-fallers
      (77.8 +/- 0.53 years old) participated in the study. Balance measurements were
      made in the upright position in six different conditions using a force platform,
      and the Limits of Stability Test was carried out. Static two-point discrimination
      (TPD) testing to the underside of the first toe was made to evaluate the
      innervation density of the slowly adapting receptors. Finally, maximal isometric
      lower limb strength was measured in major muscle groups. Repeated measures
      analysis of variance tests were performed to assess the mean differences between
      the two groups (fallers and non-fallers). The level of significance was set to
      0.05. RESULTS AND DISCUSSION: results suggest that control of balance in narrow
      base stance may be an important tool in identifying elderly fallers. The findings
      show an increase in mediolateral sway in narrow base stance in older people who
      experienced recurrent falls. Also, TPD appears to be impaired in elderly fallers
      (14.93 +/- 1.1 mm versus 12.98 +/- 0.3 mm). CONCLUSIONS: simple and safe
      laboratory quantitative tests were able to differentiate between elderly fallers
      and elderly individuals who did not fall, suggesting a possible clinical
      application as a preliminary screening tool for predicting future risk of
      falling.

PMID- 15501838
TI  - Older stroke patients in Europe: stroke care and determinants of outcome.
AB  - BACKGROUND: in order to implement cost-effective stroke services for older
      patients, it is necessary to identify how stroke care is currently provided for
      these patients and how provision relates to outcome. OBJECTIVES: to estimate the
      structure and process of care, and identify independent factors associated with 3
      month mortality and functional outcome in patients aged over 75 years compared
      with younger stroke patients across Europe. SETTING: 13 hospitals in 10 European
      countries. SUBJECTS AND METHODS: 1,847 subjects with first in a lifetime stroke
      admitted to hospital. Sociodemographic details, acute case severity, resource use
      and 3-month survival and dependency were collected. RESULTS: from a total of
      1,847 patients, 1,112 patients (60%) were under 75 years. Older stroke patients
      were more likely to be incontinent, dysphasic, dysphagic and comatose (P <
      0.001). Computed tomography scan rates were higher in younger (87%) than in older
      patients (79%) (P < 0.001). Access to organised stroke care was higher in older
      (58%) than in younger patients (51%) (P = 0.002). Median acute length of stay was
      longer in younger (14 days, range 7-21 days) than in older patients (11 days,
      range 8-22 days) (P = 0.04). Nursing time in hospital was higher in older
      patients (P = 0.01), whilst therapy time was higher in younger patients (P =
      0.03). By 3 months, younger patients were more likely to receive outpatient care
      (P < 0.001), physiotherapy (P < 0.001) and occupational therapy (P < 0.001). For
      older stroke patients, not having a computed tomography scan (OR = 0.2, 95%
      confidence intervals (CI) = 0.01-0.6, P = 0.003) was significantly related to
      mortality at 3 months after adjusting for case mix. Access to organised stroke
      care was significantly associated with reduced 3-month mortality in younger
      patients only (OR = 0.29, 95% CI = 0.14-0.6, P < 0.001). CONCLUSION: stroke care
      varies considerably across European centres, with older people more likely to
      gain access to organised stroke care in many centres but less likely to receive
      diagnostic investigations, therapy input and outpatient review. Where there is
      evidence of age discrimination for access to stroke services, guidelines need to
      be adopted to ensure patients of all ages receive optimal evidence-based stroke
      care at all stages of their illness.

PMID- 15501839
TI  - Towards a good death: the impact of the care of the dying pathway in an acute
      stroke unit.

PMID- 15501840
TI  - Are some antihypertensives more prone to induce hypotensive side effects than
      others?

PMID- 15501841
TI  - Reliability and validity of a telephone-based mobility assessment questionnaire.

PMID- 15501842
TI  - Eighteen-year trends in obesity among the elderly.

PMID- 15501843
TI  - Enoxaparin-associated spontaneous thigh haematoma.

PMID- 15501844
TI  - Are the days of bedrails coming to an end?

PMID- 15501848
TI  - The projectile tooth of a fish-hunting cone snail: Conus catus injects venom into
      fish prey using a high-speed ballistic mechanism.

PMID- 15501849
TI  - Octocoral chemical signaling selects and controls dinoflagellate symbionts.

PMID- 15501850
TI  - Phylogenetic placement of "zoochlorellae" (Chlorophyta), algal symbiont of the
      temperate sea anemone Anthopleura elegantissima.
AB  - At northern latitudes the sea anemones Anthopleura elegantissima and its congener
      A. xanthogrammica contain unidentified green chlorophytes (zoochlorellae) in
      addition to dinophytes belonging to the genus Symbiodinium. This dual algal
      symbiosis, involving members of distinct algal phyla in one host, has been
      extensively studied from the perspective of the ecological and energetic
      consequences of hosting one symbiotic type over the other. However, the identity
      of the green algal symbiont has remained elusive. We determined the phylogenetic
      position of the marine zoochlorellae inhabiting A. elegantissima by comparing
      sequence data from two cellular compartments, the nuclear 18S ribosomal RNA gene
      region and the plastid-encoded rbcL gene. The results support the inclusion of
      these zoochlorellae in a clade of green algae that form symbioses with animal
      (Anthopleura elegantissima), fungal (the lichen genus Nephroma), and seed plant
      (Ginkgo) partners. This clade is distinct from the Chlorella symbionts of Hydra.
      The phylogenetic diversity of algal hosts observed in this clade indicates a
      predisposition for this group of algae to participate in symbioses. An
      integrative approach to the study of these algae, both within the host and in
      culture, should yield important clues about how algae become symbionts in other
      organisms.

PMID- 15501851
TI  - Patterns in early embryonic motility: effects of size and environmental
      temperature on vertical velocities of sinking and swimming echinoid blastulae.
AB  - Early embryonic swimming is widespread among marine invertebrates, but
      quantitative information about swimming behaviors is scarce. Swimming may affect
      encounters with predators, positioning in the water column, and nutrient
      absorption. Measured rates and patterns of swimming and sinking for blastulae of
      four eastern Pacific echinoid species show that sinking speeds equal or exceed
      swimming speeds. Swimming speed scaled negatively with embryo size, though
      sinking speed did not scale with size. Analysis of swimming paths of
      Strongylocentrotus franciscanus revealed a temperature dependency in swimming
      pattern that affected speed of upward movement. Sinking speeds were significantly
      greater at 10 degrees C than at 14 degrees C for blastulae of all four species
      examined. In Dendraster excentricus, killing the blastulae annulled this
      temperature effect, indicating an active density regulation by these embryos.
      Finally, measurements of particle velocities around sinking and swimming D.
      excentricus blastulae show that swimming creates a more localized disturbance
      than sinking. Embryonic swimming may therefore decrease rather than increase
      encounters with pelagic predators. Results from subsequent experiments in which
      embryos were reared in low-oxygen environments suggest that any oxygen-absorption
      advantages of swimming have little, if any, effect on the development of D.
      excentricus embryos.

PMID- 15501852
TI  - A waterborne behavioral cue for the actinotroch larva of Phoronis pallida
      (Phoronida) produced by Upogebia pugettensis (Decapoda: Thalassinidea).
AB  - Phoronis pallida (Phoronida) occurs as a commensal within the burrow of Upogebia
      pugettensis (Decapoda: Thalassinidea). Upogebia-conditioned seawater (UCSW)
      induced an exploratory swimming behavior in competent larvae of P. pallida in a
      dosage-dependent manner. This behavior included a significant increase in
      swimming speed that was directed downward, along with the repeated probing of the
      bottom with the sensory portion of the oral hood. The waterborne cue from the
      shrimp was present in the gut effluent, and the swimming behavior was not the
      result of the elevated ammonia concentration. Molecular weight separation of the
      UCSW estimated that the cue was between 10 and 50 kDa. Enzymatic treatments
      showed that the cue's activity could be eliminated by arginase and significantly
      reduced by lipase. Competent larvae were also induced to metamorphose when
      exposed to 20 mM CsCl for 30 min. Larvae did not respond to CsCl when cultured
      about 4 weeks past the onset of competence. Compared with actinotroch larvae of
      other phoronid species, P. pallida larvae exhibit greater behavioral specificity
      and neuronal differences within the hood sense organ. These anatomical and
      behavioral differences may have been maintained through a coevolutionary process
      among P. pallida and species of thalassinid shrimps that share Upogebia life
      history characteristics.

PMID- 15501853
TI  - Microscaling: why larger anemones have longer cnidae.
AB  - Scaling analysis provides a quantitative method for describing and comparing how
      qualities of organisms vary as a function of body size. However, cell level
      phenomena have been notoriously hard to analyze because animal cells and
      organelles have such irregular shapes. The intracellular cnidae make good models
      of scaling at the cell level because they are durable and easy to image and
      measure. The mean length of unfired tentacle cnidae (spirocysts) varies
      continuously, and reversibly, with body size for three macrophagous anemone
      species. Significant differences in spirocyst shape and size relative to body
      mass are related to differences in tissue functions and species ecologies,
      strongly suggesting that cnida size, shape, and scaling patterns respond to
      natural selection. Cnida scaling patterns can be treated as features of cnidarian
      life histories. Spirocyst scaling exponents (slopes of log cnida dimension vs.
      log body weight) are similar to each other (0.05-0.09) and to reported values for
      animal somatic cells (0.017-0.17), but are much smaller than reported values for
      anemone basal diameters (0.30-0.38). I propose, here, a general, mechanical
      explanation for microscaling of structural secretory cells and their secretions,
      including the cnidae. Larger bodies require thicker, pliant sheets of sluggishly
      respiring extracellular support materials such as mesoglea and basement membrane.
      Thicker mesoglea can support larger, taller epithelial cells, which in turn
      provide additional maintenance services for these progressively thicker acellular
      layers. Ultimately, larger, taller cells can secrete and support larger, longer
      cnidae.

PMID- 15501854
TI  - Predation resistance and nematocyst scaling for Metridium senile and M. farcimen.
AB  - Previous studies suggest that large body size reduces the risk of predation for
      acontiate sea anemones. For two species of Metridium, we found significant
      increases in the length of the acontial threads and in the mean lengths of the
      unfired acontial nematocyst capsules, with increasing body size. This supports
      the hypothesis that more damaging acontial defenses protect larger acontiate
      anemones from their predators. Metridium is planktivorous, and food size does not
      increase substantially with body size; so we expected smaller increases in
      nematocyst size for the feeding tentacles. In fact, scaling exponents were
      significantly smaller for the tentacle nematocysts than for acontial nematocysts
      of the same types in 3 out of 4 cases. This suggests that nematocyst scaling
      responds predictably to selection pressure. When specimens of the same size were
      compared, the non-clonal, subtidal species, M. farcimen, had significantly larger
      acontial nematocysts than did its clonal congener, M. senile, which lives at the
      upper tidal limits for major subtidal predators in the northeastern Pacific.
      Therefore, larger acontial nematocysts may be particularly advantageous where
      predation levels are high. These data demonstrate that closely related anemone
      species can be distinguished on the basis of ecologically and functionally
      relevant differences in nematocyst scaling.

PMID- 15501855
TI  - Evidence for a common pattern of peptidergic innervation of cnidocytes.
AB  - Tentacles from representatives of all four classes of the phylum Cnidaria were
      examined using antibodies against the neuropeptides FMRFamide and RFamide to
      reveal the organization of neurons and nerve nets associated with cnidocytes. The
      tentacles of all species examined contained FMRFamide- or RFamide-immunoreactive
      neurons, in varying densities. In representatives from the Scyphozoa, Hydrozoa,
      and Cubozoa, the FMRFamide-immunoreactive neurons formed plexuses at the base of
      the cnidocyte assemblages; in anthozoans, the absence of discrete assemblies of
      cnidocytes precluded visual co-localization of cnidocytes and immunoreactive
      neurons. In all four classes, immunoreactive sensory cells connected these
      peptidergic nerve nets to the surface of the tentacle. These findings suggest
      that members of all four cnidarian classes share a common organizational pattern,
      and it is proposed that this peptidergic innervation may be involved in the
      chemosensory regulation of cnidocyte discharge.

PMID- 15501901
TI  - Paternal age and schizophrenia: a population based cohort study.
AB  - OBJECTIVE: To investigate the association of paternal age at conception with the
      risk of offspring developing schizophrenia. DESIGN: A population based cohort
      study. SETTING: Sweden. SUBJECTS: 754,330 people born in Sweden between 1973 and
      1980 and still alive and resident in Sweden at age 16 years. MAIN OUTCOME
      MEASURES: Hospital admission with schizophrenia or non-schizophrenic, non
      affective psychosis. RESULTS: After adjustment for birth related exposures,
      socioeconomic factors, family history of psychosis, and early parental death the
      overall hazard ratio for each 10 year increase in paternal age was 1.47 (95%
      confidence interval 1.23 to 1.76) for schizophrenia and 1.12 (0.98 to 1.29) for
      non-schizophrenic non-affective psychosis. This association between paternal age
      and schizophrenia was present in those with no family history of the disorder
      (hazard ratio for each 10 year increase in paternal age 1.60, 1.32 to 1.92), but
      not in those with a family history (0.91, 0.44 to 1.89) (P = 0.04 for
      interaction). CONCLUSIONS: Advancing paternal age is an important independent
      risk factor for schizophrenia. The stronger association between paternal age and
      schizophrenia in people without a family history provides further evidence that
      accumulation of de novo mutations in paternal sperm contributes to the overall
      risk of schizophrenia.

PMID- 15501902
TI  - Progesterone inhibits insulin-like growth factor binding protein-1 (IGFBP-1)
      production by explants of the Fallopian tube.
AB  - The Fallopian tube provides the environment for early embryo growth, a process
      which is influenced by insulin-like growth factors (IGFs) in the tubal fluid.
      Whether the bioavailability of tubal IGFs is modulated by locally produced IGF
      binding protein (IGFBP-1) is not clear. An explant culture system from human
      Fallopian tube mucosa was, therefore, developed enabling the potential for IGFBP
      1 production by this tissue to be examined directly. Initial characterization of
      the system established that the explants maintained responsiveness to steroids.
      Thus, oviduct-specific glycoprotein production, a major product of the oviduct in
      vivo, continued to be made via an estrogen-sensitive pathway in the culture. The
      presence of mRNA for IGFBP-1 was established within the explants by the use of
      quantitative RT-PCR and IGFBP-1 protein was measured by enzyme-linked
      immunosorbent assay. Although insulin and estradiol had no consistent effect on
      IGFBP-1, addition of progesterone had a significant inhibitory effect on IGFBP-1
      production, both at the mRNA and protein levels. A dose-range of progesterone
      revealed an incremental inhibitory effect of progesterone on IGFBP-1 output
      (maximal effect, 25-50 nmol/l), consistent with physiological inhibition of this
      process during the luteal phase. We suggest that progesterone might, therefore,
      play a role in controlling the bioavailability of IGFs to the embryo during early
      development within the Fallopian tube.

PMID- 15501903
TI  - Molecular classification of human endometrial cycle stages by transcriptional
      profiling.
AB  - Endometrium is a dynamic tissue that undergoes cyclic changes each month, under
      the overall control of estrogen and progesterone. The aims of this study were to
      investigate the changing global gene expression profile of human endometrium
      during the menstrual cycle using microarray technology and to determine the
      correlation between histopathological evaluation and molecular profile of the
      samples. Standard two-colour cDNA microarrays were performed on the 43 samples
      against a common reference, using a 10.5 K cDNA glass slide microarray. The
      results were validated using real-time PCR. Analysis of expression data was
      carried out using parametric analysis of variance with Benjamini-Hochberg
      correction. Hierarchical clustering reveals a strong relationship between
      histopathology and transcriptional profile of the samples. The study identified
      1452 genes that showed significant changes in expression (P< or =0.05) across the
      menstrual cycle, with 425 genes having changes that are at least 2-fold. The data
      were also independently analysed by a CSIRO algorithm called GeneRaVE that
      identified a small subset of genes whose expression profiles could be used to
      classify nearly all the biopsies into their correct cycle stage. We also
      identified and validated three genes [(natural cytotoxicity triggering receptor
      (NCR)3, fucosyl transferase (FUT)4 and Fyn-binding protein (FYB)] that had not
      been shown to have significant cyclic changes in the human endometrium,
      previously. We have shown for the first time that endometrial cycle stage
      prediction is possible based on global gene expression profile.

PMID- 15501904
TI  - FOXO1 and c-jun transcription factors mRNA are modulated in endometriosis.
AB  - Endometriosis is a polygenic gynaecological condition affecting 5-15% of women of
      childbearing age. Major symptoms of the disease are pelvic pain and infertility.
      No clear link has been established between symptoms and the stage of the disease.
      Although some aspects have begun to be clarified, clinical understanding of
      endometriosis remains partial at the molecular level. In this perspective, we
      targeted isolation of differentially expressed genes in the eutopic endometrial
      tissue. Our assumption was that the endometrial cells of patients presented an
      unusual gene expression profile, allowing their implantation and survival in an
      ectopic site, leading to endometriotic lesions. Here, we report that mRNA steady
      state levels of two key transcription factors are modulated in endometriosis.
      FOXO1 (also known as FKHR) levels were 1.6-fold lower in endometriosis compared
      to the control group at the onset of the secretory phase (day 15-21), while c-jun
      mRNA was present at higher amounts in endometriosis (1.5-fold) at the
      proliferative phase of the menstrual cycle. These results were derived from a
      large sample composed of 157 control subjects and 209 patients with
      endometriosis. Gene profiling was conducted by real-time quantitative PCR, and
      data were quality controlled before statistical analysis. Whether protein levels
      are affected as well remains to be investigated.

PMID- 15501905
TI  - Haplotypic association of DDAH1 with susceptibility to pre-eclampsia.
AB  - Association between pre-eclampsia (PEE1) and the dimethylarginine
      dimethylaminohydrolase (DDAH) 1 and 2 genes, which play a role in the regulation
      of nitric oxide synthesis and release, was studied. In a case-control study
      design single nucleotide polymorphisms (SNPs) were determined at eight sites in
      the DDAH1 gene and at one site (Pro231Pro) in the DDAH2 gene from 132 women with
      pre-eclampsia and 112 healthy controls. Three SNPs in the DDAH1 gene were
      associated with pre-eclampsia, showing complete linkage disequilibrium with each
      other, but none of the associations in the allele or genotype data reached
      statistical significance in either of the genes after the correction for multiple
      testing. Haplotype frequencies were estimated using a population based on a
      maximum likelihood method (EM algorithm). Four common DDAH1 haplotypes were
      present and a significant association of haplotypes H2 and H3 with pre-eclampsia
      (P=0.03) was found. The risk of pre-eclampsia was greatest in individuals (odds
      ratio: 3.93; 95% confidence interval: 1.54-9.99) who had two copies of the high
      risk haplotypes (H2 or H3). The observed haplotypic association provides the
      first evidence of the importance of DDAH1 polymorphisms in pre-eclampsia
      susceptibility.

PMID- 15501906
TI  - Slowly reversible de-epoxidation of lutein-epoxide in deep shade leaves of a
      tropical tree legume may 'lock-in' lutein-based photoprotection during
      acclimation to strong light.
AB  - The kinetics of response to strong light have been examined in deeply shaded
      leaves of the tropical tree legume (Inga sp.) which have extraordinarily high
      levels of the alpha-xanthophyll lutein-epoxide that are co-located in pigment
      protein complexes of the photosynthetic apparatus with the beta-xanthophyll
      violaxanthin. As in other species, rapidly reversible photoprotection (measured
      as non-photochemical chlorophyll fluorescence quenching) is initiated within the
      time frame of sun-flecks (minutes), before detectable conversion of violaxanthin
      to antheraxanthin or zeaxanthin. Photoprotection is stabilized within hours of
      exposure to strong light by simultaneously engaging the reversible violaxanthin
      cycle and a slowly reversible conversion of lutein-epoxide to lutein. It is
      proposed that this lutein 'locks in' a primary mechanism of photoprotection
      during photoacclimation in this species, converting efficient light-harvesting
      antennae of the shade plant into potential excitation dissipating centres. It is
      hypothesized that lutein occupies sites L2 and V1 in light-harvesting chlorophyll
      protein complexes of photosystem II, facilitating enhanced photoprotection
      through the superior singlet and/or triplet chlorophyll quenching capacity of
      lutein.

PMID- 15501907
TI  - Phosphate deficiency regulates phosphoenolpyruvate carboxylase expression in
      proteoid root clusters of white lupin.
AB  - Proteoid roots play a major role in enabling white lupin (Lupinus albus L.) to
      adapt to phosphate (Pi) deficiency. Such roots release citrate from proteoid
      rootlets, which allows this species to mobilize Pi from sparingly soluble Pi
      sources. Release of citrate is preceded by a significant accumulation of organic
      acids, in which a Pi deficiency-inducible phosphoenolpyruvate carboxylase (PEPC)
      activity has been involved. To gain an insight into this adaptive mechanism, the
      expression of three different transcripts coding for PEPC was examined in
      proteoid rootlets of Pi-starved and Pi-starved-and-rescued white lupin. Semi
      quantitative reverse transcriptase (RT)-PCR experiments performed with gene
      specific primers targeted to the 3'-end region of the corresponding cDNAs
      revealed that the transcripts for these three PEPCs differentially accumulate in
      both Pi-starved and Pi-starved-and-rescued proteoid rootlets. Semi-quantitative
      RT-PCR analysis in Pi-starved proteoid rootlets sampled at different times after
      being rescued from Pi deficiency showed that Pi levels differentially down
      regulated the three PEPC transcripts. RT-PCR experiments were further extended to
      Pi-starved and Pi-fed whole roots, cotyledons, and leaves on which a tissue
      specific, Pi-dependent PEPC expression was observed. These results indicate that
      there exists at least three different transcripts coding for PEPC in proteoid
      root clusters of white lupin, whose expression are differentially regulated by
      Pi.

PMID- 15501908
TI  - Glutamate synthase activities and protein changes in relation to nitrogen
      nutrition in barley: the dependence on different plastidic glucose-6P
      dehydrogenase isoforms.
AB  - In barley (Hordeum vulgare L. var. Nure), glutamate synthesis and the production
      of reducing power by the oxidative pentose phosphate pathway (OPPP) are strictly
      correlated biochemical processes. NADH-GOGAT was the major root isoform, whose
      activity increased on a medium supplied with NH4+ or NO3-; by contrast, no
      noticeable variations could be observed in the leaves of plants supplied with
      nitrogen. In the leaves, the major isoform is Fd-GOGAT, whose activity increased
      under nitrogen feeding. G6PDH activity increased in the roots supplied with
      nitrogen; no variations were observed in the leaves. Moreover, an increase of the
      P2 isoform in the roots was measured, giving 13.6% G6PDH activity localized in
      the plastids under ammonium, and 25.2% under nitrate feeding conditions. Western
      blots confirmed that P2-G6PDH protein was induced in the roots by nitrogen. P1
      G6PDH protein was absent in the roots and increased in the leaves by nitrogen
      supply to the plants. The changes measured in cytosolic G6PDH seem correlated to
      more general cell growth processes, and do not appear to be directly involved in
      glutamate synthesis. The effects of light on Fd-GOGAT is discussed, together with
      the possibility for P2-G6PDH to sustain nitrogen assimilation upon illumination.

PMID- 15501909
TI  - A centromeric region on chromosome 6(6H) affects dormancy in an induced mutant in
      barley.
AB  - Genetic control of seed dormancy in barley (Hordeum vulgare L.) has mostly been
      described in terms of quantitative variation. Although some molecular markers for
      dormancy QTL have been identified, the corresponding genes involved in the
      regulation of the process have not been cloned. Induced barley mutants may
      constitute useful material to study the physiology and genetics of seed dormancy.
      The objective of this study was to identify the genetic control of this trait in
      a mutant (TL43) produced in the barley cv. Triumph. This mutant was selected for
      reduced dormancy and reduced sensitivity to abscisic acid (ABA). Two sets of F6
      barley lines were selected for high and low levels of dormancy from a cross
      between the original dormant parent and the sodium azide-induced non-dormant TL43
      mutant. Unexpectedly, given the near-isogenic nature of these two genotypes,
      polymorphism was detected for an SSR located in the centromeric region of
      chromosome 6(6H) out of a total of 92 molecular markers evenly distributed along
      the genome. Fortunately, upon three cycles of intensive divergent selection,
      every dormant and non-dormant F5 line consistently showed the genotype for this
      region identical to Triumph and TL43, respectively. Based on the mutagenic effect
      presumably attributed to sodium azide, mostly single point mutations, it cannot
      be clearly established if such extensive genomic variation on chromosome 6(6H) is
      due to the mutagenic treatment or may be an introgression from an unknown source.
      The means that could originate such heterogeneity are discussed; however,
      regardless of its origin, this genomic region shows a strong association with the
      expression of seed dormancy and provides an additional genetic locus for further
      studies of the mechanistic basis of this complex trait. In addition, since TL43
      shows reduced sensitivity to ABA, the response to this hormone was determined on
      the F6 seed from the two sets of selected F5 lines. The results confirmed that
      the initial level of dormancy in the seed lot is the most important factor in
      determining ABA sensitivity.

PMID- 15501910
TI  - Molecular and biochemical characterization of LeCRK1, a ripening-associated
      tomato CDPK-related kinase.
AB  - A cDNA clone (LeCRK1), encoding a novel isoform of calcium-dependent protein
      kinase (CDPK), was isolated by screening a tomato (Lycopersicon esculentum) cDNA
      library. The protein derived from the full-length sequence indicated that it
      belongs to the family of CDPK-related kinases (CRKs) and the predicted amino acid
      sequence shows a modular organization of the protein consisting of different
      characteristic domains. The kinase domain of LeCRK1 shares a high degree of
      similarity with the catalytic domain of CDPKs. In contrast to canonical members
      of the family, LeCRK1 has a degenerate sequence in the C-terminal calmodulin-like
      domain. LeCRK1 protein was shown to be a functional kinase, but, consistent with
      the lack of calcium-binding activity, its autophosphorylation activity did not
      require calcium. LeCRK1 harbours an amphiphilic amino acid region revealed to be
      a functional calmodulin-binding site by in vitro assay. A putative
      myristoylation/palmitoylation sequence has been identified at the N-terminus.
      Expressing an LeCRK1::GFP fusion protein in the protoplast resulted in its
      targeting to the plasma membrane. Site-directed mutagenesis of critical amino
      acids of the myristoylation/palmitoylation consensus sites led to the
      accumulation of the mutated protein in the cytoplasm, suggesting that the native
      protein is anchored to the plasma membrane by acylated residues. Expression
      studies revealed significant accumulation of LeCRK1 transcripts during fruit
      ripening, although transcripts were also detected in stem, leaf, and flower.
      LeCRK1 mRNA level in leaves was slightly induced by ethylene and salicylic acid,
      and upon mechanical wounding and cold treatment. It is noteworthy that LeCRK1
      mRNAs were undetectable in different tomato-ripening natural mutants such as NR,
      Rin, and Nor, suggesting a role in the ripening process.

PMID- 15501911
TI  - Ectopic expression of Arabidopsis CYCD2 and CYCD3 in tobacco has distinct effects
      on the structural organization of the shoot apical meristem.
AB  - Transgenic tobacco lines expressing Arath-CYCD2 or Arath-CYCD3 genes under a
      cauliflower mosaic virus 35S promoter are modified in the timing of their
      development, but not in the phenotype of their vegetative organs. They display an
      increased rate of leaf initiation, which is shown to be associated with distinct
      changes in the structural organization of their shoot apical meristem (SAM).
      Constitutive expression of Arath-CYCD2 leads to a progressive modification of the
      SAM structural organization with predominant periclinal divisions in the L3 layer
      and to the loss of the classical cytophysiological zonation, the central zone
      being reduced to the central cells of the L1 and L2 layers. These changes reveal
      a particular sensitivity of the corpus cells (L3) to Arath-CYCD2 over-expression
      and suggest a role for CYCD2 in controlling the planes of cell division in these
      cells. The SAM structural modifications in the Arath-CYCD3 over-expressing lines
      are less drastic; only an increased cell number together with a reduced cell
      size, particularly in the L1 layer, characterizes the peripheral zones. This
      could be related to the shortening of the G1-phase duration that renders cell
      growth incomplete between successive mitoses. Cell proliferation continues beyond
      the SAM in the developing internodes and confers a delayed senescence to Arath
      CYCD3 over-expressing juvenile tissues. In addition, the ploidy levels of mature
      stem tissues in both types of transgenic lines are unaffected, suggesting that
      the studied G1 to S cell-cycle genes have no effect on the extent of
      endoreduplication in tobacco stem tissues.

PMID- 15501912
TI  - A/C(i) curve analysis across a range of woody plant species: influence of
      regression analysis parameters and mesophyll conductance.
AB  - The analysis and interpretation of A/C(i) curves (net CO(2) assimilation rate, A,
      versus calculated substomatal CO(2) concentration, C(i)) is dependent upon a
      number of underlying assumptions. The influence of the C(i) value at which the
      A/C(i) curve switches between the Rubisco- and electron transport-limited
      portions of the curve was examined on A/C(i) curve parameter estimates, as well
      as the effect of mesophyll CO(2) conductance (g(m)) values on estimates of the
      maximum rate of Rubisco-mediated carboxylation (V(cmax)). Based on an analysis
      using 19 woody species from the Pacific Northwest, significant variation occurred
      in the C(i) value where the Rubisco- and electron transport-limited portions of
      the curve intersect (C(i_t)), ranging from 20 Pa to 152 Pa and averaging c. 71 Pa
      and 37 Pa for conifer and broadleaf species, respectively. Significant effects on
      estimated A/C(i) parameters (e.g. V(cmax)) may arise when preliminary estimates
      of C(i_t), necessary for the multiple regression analyses, are set either too
      high or too low. However, when the appropriate threshold is used, a significant
      relationship between A/C(i) and chlorophyll fluorescence estimates of
      carboxylation is achieved. The use of the V(cmax) parameter to describe
      accurately the Rubisco activity from the A/C(i) curve analysis is also dependent
      upon the assumption that C(i) is approximately equal to chloroplast CO(2)
      concentrations (C(c)). If leaf mesophyll conductance is low, C(c) will be much
      lower than C(i) and will result in an underestimation of V(cmax) from A/C(i)
      curves. A large range of mesophyll conductance (g(m)) values was observed across
      the 19 species (0.005+/-0.002 to 0.189+/-0.011 mol m(-2) s(-1) for Tsuga
      heterophylla and Quercus garryana, respectively) and, on average, g(m) was 1.9
      times lower for the conifer species (0.058+/-0.017 mol m(-2) s(-1) for conifers
      versus 0.112+/-0.020 mol m(-2) s(-1) for broadleaves). When this mesophyll
      limitation was accounted for in V(cmax) estimates, considerable variation still
      existed between species, but the difference in V(cmax) between conifer and
      broadleaf species was reduced from c. 11 micromol m(-2) s(-1) to 4 micromol m(-2)
      s(-1). For example, A/C(i) curve estimates of V(cmax) were 31.2+/-6.2 and 42.2+/
      4.4 micromol m(-2) s(-1), and A/C(c) curve estimates were 41.2+/-7.1 micromol m(
      2) s(-1) and 45.0+/-4.8 micromol m(-2) s(-1), for the conifer and broadleaf
      species, respectively.

PMID- 15501913
TI  - Comparison of different melting temperature calculation methods for short DNA
      sequences.
AB  - MOTIVATION: The overall performance of several molecular biology techniques
      involving DNA/DNA hybridization depends on the accurate prediction of the
      experimental value of a critical parameter: the melting temperature Tm. Till
      date, many computer software programs based on different methods and/or
      parameterizations are available for the theoretical estimation of the
      experimental Tm value of any given short oligonucleotide sequence. However, in
      most cases, large and significant differences in the estimations of Tm were
      obtained while using different methods. Thus, it is difficult to decide which Tm
      value is the accurate one. In addition, it seems that most people who use these
      methods are unaware about the limitations, which are well described in the
      literature but not stated properly or restricted the inputs of most of the web
      servers and standalone software programs that implement them. RESULTS: A
      quantitative comparison on the similarities and differences among some of the
      published DNA/DNA Tm calculation methods is reported. The comparison was carried
      out for a large set of short oligonucleotide sequences ranging from 16 to 30 nt
      long, which span the whole range of CG-content. The results showed that
      significant differences were observed in all the methods, which in some cases
      depend on the oligonucleotide length and CG-content in a non-trivial manner.
      Based on these results, the regions of consensus and disagreement for the methods
      in the oligonucleotide feature space were reported. Owing to the lack of
      sufficient experimental data, a fair and complete assessment of accuracy for the
      different methods is not yet possible. Inspite of this limitation, a consensus Tm
      with minimal error probability was calculated by averaging the values obtained
      from two or more methods that exhibit similar behavior to each particular
      combination of oligonucleotide length and CG-content class. Using a total of 348
      DNA sequences in the size range between 16mer and 30mer, for which the
      experimental Tm data are available, we demonstrated that the consensus Tm is a
      robust and accurate measure. It is expected that the results of this work would
      be constituted as a useful set of guidelines to be followed for the successful
      experimental implementation of various molecular biology techniques, such as
      quantitative PCR, multiplex PCR and the design of optimal DNA microarrays.

PMID- 15501914
TI  - PSORTb v.2.0: expanded prediction of bacterial protein subcellular localization
      and insights gained from comparative proteome analysis.
AB  - MOTIVATION: PSORTb v.1.1 is the most precise bacterial localization prediction
      tool available. However, the program's predictive coverage and recall are low and
      the method is only applicable to Gram-negative bacteria. The goals of the present
      work are as follows: increase PSORTb's coverage while maintaining the existing
      precision level, expand it to include Gram-positive bacteria and then carry out a
      comparative analysis of localization. RESULTS: An expanded database of proteins
      of known localization and new modules using frequent subsequence-based support
      vector machines was introduced into PSORTb v.2.0. The program attains a precision
      of 96% for Gram-positive and Gram-negative bacteria and predictive coverage
      comparable to other tools for whole proteome analysis. We show that the
      proportion of proteins at each localization is remarkably consistent across
      species, even in species with varying proteome size. AVAILABILITY: Web-based
      version: http://www.psort.org/psortb. Standalone version: Available through the
      website under GNU General Public License. CONTACT: psort-mail@sfu.ca,
      brinkman@sfu.ca SUPPLEMENTARY INFORMATION:
      http://www.psort.org/psortb/supplementaryinfo.html.

PMID- 15501915
TI  - Chromatin immunoprecipitation (ChIP) scanning identifies primary glucocorticoid
      receptor target genes.
AB  - The global physiological effects of glucocorticoids are well established, and the
      framework of transcriptional regulation by the glucocorticoid receptor (GR) has
      been described. However, the genes directly under GR control that trigger these
      physiological effects are largely unknown. To address this issue in a single cell
      type, we identified glucocorticoid-responsive genes in A549 human lung
      adenocarcinoma cells by microarray analysis and quantitative real-time PCR.
      Reduction of GR expression by RNA interference diminished the effects of
      dexamethasone on all tested target genes, thus confirming the essential role of
      GR in glucocorticoid-regulated gene expression. To identify primary GR target
      genes, in which GR is a component of the transcriptional regulatory complex, we
      developed a strategy that uses chromatin immunoprecipitation to scan putative
      regulatory regions of target genes for sites occupied by specifically bound GR.
      We screened 11 glucocorticoid-regulated genes, and we identified GR-binding
      regions for eight of them (five induced and three repressed). Thus, our approach
      provides a means for rapid identification of primary GR target genes and
      glucocorticoid-response elements, which will facilitate analyses of
      transcriptional regulatory mechanisms and determination of hormone-regulated gene
      networks.

PMID- 15501916
TI  - Formation of deletions during double-strand break repair in Drosophila DmBlm
      mutants occurs after strand invasion.
AB  - Bloom syndrome is a rare disorder associated with cancer predisposition and
      genomic instability and is caused by loss of the RecQ helicase BLM. The
      Drosophila ortholog of BLM (DmBlm) is required for accurate repair of DNA double
      strand gaps by homologous recombination. Repair products from DmBlm mutants have
      shorter repair synthesis tract lengths compared to wild type and are frequently
      associated with deletions flanking the break site. To determine the mechanisms
      responsible for deletion formation in the absence of DmBlm, we characterized
      repair after excision of the P[w(a)] element in various genetic backgrounds.
      Flies lacking DmRad51 do not have an elevated deletion frequency. Moreover, loss
      of DmRad51 suppresses deletion formation in DmBlm mutants. These data support a
      model in which DmBlm acts downstream of strand invasion to unwind a D-loop
      intermediate to free the newly synthesized strand. In the absence of DmBlm,
      alternative pathways of D-loop disassembly result in short repair synthesis
      tracts or flanking deletions. This model explains how RecQ helicases can promote
      homologous recombination while preventing illegitimate recombination.

PMID- 15501917
TI  - The relationship between regional and local species diversity in marine benthic
      communities: a global perspective.
AB  - The number of species coexisting in ecological communities must be a consequence
      of processes operating on both local and regional scales. Although a great deal
      of experimental work has been devoted to local causes of diversity, little is
      known about the effects of regional processes on local diversity and how they
      contribute to global diversity patterns in marine systems. We tested the effects
      of latitude and the richness of the regional species pool on the species richness
      of local epifaunal invertebrate communities by sampling the diversity of local
      sites in 12 independent biogeographic regions from 62 degrees S to 63 degrees N
      latitude. Both regional and local species richness displayed significant unimodal
      patterns with latitude, peaking at low latitudes and decreasing toward high
      latitudes. The latitudinal diversity gradient was represented at the scale of
      local sites because local species richness was positively and linearly related to
      regional species richness. The richness of the regional species pool explained 73
      76% of local species richness. On a global scale, the extent of regional
      influence on local species richness was nonrandom-the proportion of regional
      biota represented in local epifaunal communities increased significantly from low
      to high latitudes. The strong effect of the regional species pool implies that
      patterns of local diversity in temperate, tropical, and high-latitude marine
      benthic communities are influenced by processes operating on larger
      spatiotemporal scales than previously thought.

PMID- 15501918
TI  - Crystal structure of the dimeric protein core of decorin, the archetypal small
      leucine-rich repeat proteoglycan.
AB  - Decorin is a ubiquitous extracellular matrix proteoglycan with a variety of
      important biological functions that are mediated by its interactions with
      extracellular matrix proteins, cytokines, and cell surface receptors. Decorin is
      the prototype of the family of small leucine-rich repeat proteoglycans and
      proteins (SLRPs), characterized by a protein core composed of leucine-rich
      repeats (LRRs), flanked by two cysteine-rich regions. We report here the crystal
      structure of the dimeric protein core of decorin, the best characterized member
      of the SLRP family. Each monomer adopts the curved solenoid fold characteristic
      of LRR domains, with a parallel beta-sheet on the inside interwoven with loops
      containing short segments of beta-strands, 3(10) helices, and polyproline II
      helices on the outside. Two main features are unique to this structure. First,
      decorin dimerizes through the concave surfaces of the LRR domains, which have
      been implicated previously in protein-ligand interactions. The amount of surface
      buried in this dimer rivals the buried surfaces of some of the highest-affinity
      macromolecular complexes reported to date. Second, the C-terminal region adopts
      an unusual capping motif that involves a laterally extended LRR and a disulfide
      bond. This motif seems to be unique to SLRPs and has not been observed in any
      other LRR protein structure to date. Possible implications of these features for
      decorin ligand binding and SLRP function are discussed.

PMID- 15501919
TI  - A reexamination of the evidence for the somatic marker hypothesis: what
      participants really know in the Iowa gambling task.
AB  - Bechara, Damasio, and coworkers [Bechara, A., Damasio, H., Tranel, D. & Damasio,
      A. R. (1997) Science 275, 1293-1295] have reported that normal participants
      decide advantageously before knowing the advantageous strategy in a simple card
      game designed to mimic real-life decision-making. Bechara et al. have used this
      result to support their view that nonconscious somatic markers can guide
      advantageous behavior. By using more sensitive methods, we show that participants
      have much more knowledge about the game than previously thought. In fact,
      participants report knowledge of the advantageous strategy more reliably than
      they behave advantageously. Furthermore, when they behave advantageously, their
      verbal reports nearly always reveal evidence of quantitative knowledge about the
      outcomes of the decks that would be sufficient to guide such advantageous
      behavior. In addition, there is evidence that participants also have access to
      more qualitative reportable knowledge. These results are compatible with the view
      that, in this task, both overt behavior and verbal reports reflect sampling from
      consciously accessible knowledge; there is no need to appeal to nonconscious
      somatic markers. We also discuss the findings of other studies that similarly
      suggest alternative interpretations of other evidence previously used to support
      a role for somatic markers in decision-making.

PMID- 15501920
TI  - Unidirectional translocation from recognition site and a necessary interaction
      with DNA end for cleavage by Type III restriction enzyme.
AB  - Type III restriction enzymes have been demonstrated to require two unmethylated
      asymmetric recognition sites oriented head-to-head to elicit double-strand break
      25-27 bp downstream of one of the two sites. The proposed DNA cleavage mechanism
      involves ATP-dependent DNA translocation. The sequence context of the recognition
      site was suggested to influence the site of DNA cleavage by the enzyme. In this
      investigation, we demonstrate that the cleavage site of the R.EcoP15I restriction
      enzyme does not depend on the sequence context of the recognition site.
      Strikingly, this study demonstrates that the enzyme can cleave linear DNA having
      either recognition sites in the same orientation or a single recognition site.
      Cleavage occurs predominantly at a site proximal to the DNA end in the case of
      multiple site substrates. Such cleavage can be abolished by the binding of Lac
      repressor downstream (3' side) but not upstream (5' side) of the recognition
      site. Binding of HU protein has also been observed to interfere with R.EcoP15I
      cleavage activity. In accordance with a mechanism requiring two enzyme molecules
      cooperating to elicit double-strand break on DNA, our results convincingly
      demonstrate that the enzyme translocates on DNA in a 5' to 3' direction from its
      recognition site and indicate a switch in the direction of enzyme motion at the
      DNA ends. This study demonstrates a new facet in the mode of action of these
      restriction enzymes.

PMID- 15501921
TI  - Effect of active muscle mass during ischemic exercise on peak lower leg vascular
      conductance.
AB  - Uncertainty exists as to whether a period of passive arterial occlusion (PAO) or
      ischemic exercise (IE) results in peak lower leg vascular conductance (LVC). This
      uncertainty is due to the different body positions, active muscle mass, and
      occlusion times used for PAO or IE. The purpose of this study was to examine
      whether 10 min of PAO elicits a similar LVC compared with ischemic dorsiflexion
      (IDF), ischemic plantar flexion (IPF), and ischemic plantar-dorsiflexion (IPDF).
      Ten subjects (5 women, 27 +/- 9 yr, 68 +/- 3 kg) were studied on 3 days over 1 wk
      in a semireclined position with the right foot attached to an isokinetic
      dynamometer. Mean arterial pressure (Finapres) and lower leg blood flow (LBF,
      venous occlusion plethysmography) were measured at rest and after PAO and IE. PAO
      was administered randomly on 1 of the 3 days and before IE. IE protocols
      consisted of maximal isokinetic dorsiflexion and/or plantar flexion at 120 and 60
      degrees/s, respectively. In a second experiment, an additional eight subjects (4
      women, 29 +/- 12 yr, 77 +/- 12 kg) were studied to examine the effect of
      isokinetic speed during IDF on peak LBF and LVC. Peak LVC (ml.min(-1).100 ml(
      1).mmHg(-1)) was similar among IPF (0.590 +/- 0.16), IPDF (0.532 +/- 0.17), and
      PAO (0.511 +/- 0.18), and significantly lower after IDF (0.334 +/- 0.15). No
      differences in peak LBF and LVC were observed after IDF using different
      isokinetic speeds. We conclude that 10 min of PAO, IPF, and IPDF performed in a
      similar posture are adequate stimuli to elicit peak LVC.

PMID- 15501922
TI  - Attenuation of T-lymphocyte demargination and adhesion molecule expression in
      response to moderate exercise in physically fit individuals.
AB  - The effects of physical fitness on leukocyte demargination and cellular adhesion
      molecule (CAM) responses to moderate exercise were examined. We assessed
      leukocyte subsets and CAM expression before, immediately after, and 10 min after
      a 20-min treadmill exercise at 65-70% peak oxygen consumption in fit vs. nonfit
      individuals. Physical fitness was determined by peak oxygen consumption during a
      treadmill test. Catecholamine levels were determined by radioenzymatic assay, and
      enumeration of cells and detection of CAM expression were assessed by flow
      cytometry. As expected, exercise led to significant increases in numbers of
      leukocyte subsets, regardless of fitness level (P < 0.01). Values returned to
      near resting levels 10 min after exercise. More importantly, physically fit
      individuals showed attenuated responses to the moderate-exercise challenge in
      numbers of CD3(+), CD4(+), CD8(+), memory (CD45RO(+)) CD4, and naive
      (CD45RA(+)62L(+)) CD4 and CD8 lymphocytes. Postexercise human leukocyte antigen
      DR absent memory CD4(+) cell numbers were also lower in fit subjects. Increases
      in CD62L-expressing CD4(+) and CD8(+) lymphocytes and CD11a- expressing
      lymphocytes after exercise were also attenuated in fit individuals compared with
      nonfit individuals (P < 0.05). Catecholamine levels increased to a similar extent
      (P < 0.01) in both fitness groups. The findings suggest that physical fitness
      attenuates demargination of selected lymphocyte subsets in response to moderate
      exercise. Although the differences in plasma catecholamine responses were not
      significant between the groups, a possible mediating role of the sympathetic
      system remains to be further investigated. Being physically fit may offset
      exaggerated immune cell responses to stress.

PMID- 15501923
TI  - Long-term bed rest-induced reductions in stroke volume during rest and exercise:
      cardiac dysfunction vs. volume depletion.
AB  - Long-term head-down-tilt bed rest (HDT) causes cardiovascular deconditioning,
      attributed to reflex dysfunctions, plasma volume reduction, or cardiac
      impairments. Our objective with the present study was to evaluate the functional
      importance and relative contribution of these during rest and exercise in supine
      and upright postures. We studied six subjects before (baseline), during [days 60
      (D60) and 113 (D113)], and after [recovery days 0 (R0), 3 (R3), and 15 (R15)] 120
      days of -6 degrees HDT. We determined cardiac output, stroke volume (SV), mean
      arterial pressure, and heart rate during rest and exercise in supine and upright
      postures. Cardiac output and SV decreased significantly in all four conditions,
      but the time courses differed for rest and exercise. Upright resting SV was
      decreased by 24 +/- 9% at D60 compared with baseline but had recovered already at
      R3. Supine exercise SV decreased more slowly (by 5 +/- 8% at D60 and by 18 +/- 4%
      at D113) and recovered more slowly after HDT termination. Steady-state mean
      arterial pressure showed no changes. Heart rate had increased by 18 +/- 4% at D60
      and had recovered partially at R3. Our data indicate that long-term HDT causes
      both a rapid, preload-dependent reduction in SV, most evident during rest in the
      upright position, and a more slowly developing cardiac dysfunction, most evident
      during supine exercise. However, the ability to maintain blood pressure and to
      perform sustained low levels of dynamic exercise is not influenced by HDT.

PMID- 15501924
TI  - Pressure-induced smooth muscle cell depolarization in pulmonary arteries from
      control and chronically hypoxic rats does not cause myogenic vasoconstriction.
AB  - Chronic obstructive pulmonary diseases, as well as prolonged residence at high
      altitude, can result in generalized airway hypoxia, eliciting an increase in
      pulmonary vascular resistance. We hypothesized that a portion of the elevated
      pulmonary vascular resistance following chronic hypoxia (CH) is due to the
      development of myogenic tone. Isolated, pressurized small pulmonary arteries from
      control (barometric pressure congruent with 630 Torr) and CH (4 wk, barometric
      pressure = 380 Torr) rats were loaded with fura 2-AM and perfused with warm (37
      degrees C), aerated (21% O(2)-6% CO(2)-balance N(2)) physiological saline
      solution. Vascular smooth muscle (VSM) intracellular Ca(2+) concentration
      ([Ca(2+)](i)) and diameter responses to increasing intraluminal pressure were
      determined. Diameter and VSM cell [Ca(2+)](i) responses to KCl were also
      determined. In a separate set of experiments, VSM cell membrane potential
      responses to increasing luminal pressure were determined in arteries from control
      and CH rats. VSM cell membrane potential in arteries from CH animals was
      depolarized relative to control at each pressure step. VSM cells from both groups
      exhibited a further depolarization in response to step increases in intraluminal
      pressure. However, arteries from both control and CH rats distended passively to
      increasing intraluminal pressure, and VSM cell [Ca(2+)](i) was not affected. KCl
      elicited a dose-dependent vasoconstriction that was nearly identical between
      control and CH groups. Whereas KCl administration resulted in a dose-dependent
      increase in VSM cell [Ca(2+)](i) in arteries taken from control animals, this
      stimulus elicited only a slight increase in VSM cell [Ca(2+)](i) in arteries from
      CH animals. We conclude that the pulmonary circulation of the rat does not
      demonstrate pressure-induced vasoconstriction.

PMID- 15501925
TI  - Anatomically based three-dimensional model of airways to simulate flow and
      particle transport using computational fluid dynamics.
AB  - We have studied gas flow and particle deposition in a realistic three-dimensional
      (3D) model of the bronchial tree, extending from the trachea to the segmental
      bronchi (7th airway generation for the most distal ones) using computational
      fluid dynamics. The model is based on the morphometrical data of Horsfield et al.
      (Horsfield K, Dart G, Olson DE, Filley GF, and Cumming G. J Appl Physiol 31: 207
      217, 1971) and on bronchoscopic and computerized tomography images, which give
      the spatial 3D orientation of the curved ducts. It incorporates realistic angles
      of successive branching planes. Steady inspiratory flow varying between 50 and
      500 cm(3)/s was simulated, as well as deposition of spherical aerosol particles
      (1-7 microm diameter, 1 g/cm(3) density). Flow simulations indicated nonfully
      developed flows in the branches due to their relative short lengths. Velocity
      flow profiles in the segmental bronchi, taken one diameter downstream of the
      bifurcation, were distorted compared with the flow in a simple curved tube, and
      wide patterns of secondary flow fields were observed. Both were due to the
      asymmetrical 3D configuration of the bifurcating network. Viscous pressure drop
      in the model was compared with results obtained by Pedley et al. (Pedley TJ,
      Schroter RC, and Sudlow MF. Respir Physiol 9: 387-405, 1970), which are shown to
      be a good first approximation. Particle deposition increased with particle size
      and was minimal for approximately 200 cm(3)/s inspiratory flow, but it was highly
      heterogeneous for branches of the same generation.

PMID- 15501926
TI  - Ascorbic acid does not affect the age-associated reduction in maximal cardiac
      output and oxygen consumption in healthy adults.
AB  - Maximal aerobic capacity (Vo(2max)) decreases progressively with age, primarily
      because of a reduction in maximal cardiac output (Q(max)). This age-associated
      decline in Vo(2max) may be partially mediated by the development of oxidative
      stress that can suppress beta-adrenergic-receptor responsiveness and,
      consequently, reduce Q(max). To test this hypothesis, Vo(2max) (indirect
      calorimetry) and Q(max) (open-circuit acetylene breathing) were determined in 12
      young (23 +/- 1 yr, mean +/- SE) and 10 older (61 +/- 1 yr) adults following
      systemic infusion of either saline (control) and/or the powerful antioxidant
      ascorbic acid (acute: bolus 0.06; drip 0.02 g/kg fat-free mass) and following
      chronic 30-day oral administration of ascorbic acid (500 mg/day). Plasma ascorbic
      acid concentration was not different between young and older adults and was
      increased similarly, independent of age [change (Delta) acute = 1,055 +/- 117%;
      Delta chronic = 62 +/- 19%]. Oxidized low-density lipoprotein concentration was
      greater (P < 0.001) in older (57 +/- 5 U/l) compared with young (34 +/- 3 U/l)
      adults and was reduced in both groups (P < 0.02) following acute (Delta = -6 +/-
      2%) but not chronic (P = 0.18) ascorbic acid administration. Control (baseline)
      Vo(2max) and Q(max) were positively related (r = 0.76, P < 0.001) and were lower
      (P < 0.05) in older (34 +/- 2 ml.kg(-1).min(-1); 16.1 +/- 1.1 l/min) compared
      with young (43 +/- 3 ml.kg(-1).min(-1); 20.2 +/- 0.9 l/min) adults. Following
      ascorbic acid administration, neither Vo(2max) (young acute = 41 +/- 2; young
      chronic = 42 +/- 2; older acute = 34 +/- 2; older chronic = 34 +/- 2 ml.kg(
      1).min(-1)) nor Q(max) (young acute = 20.1 +/- 0.9; young chronic = 19.1 +/- 0.8;
      older acute = 16.2 +/- 1.1; older chronic = 16.6 +/- 1.4 l/min) was changed.
      These data suggest that ascorbic acid administration does not affect the age
      associated reduction in Q(max) and Vo(2max).

PMID- 15501927
TI  - Activation of phosphatidylinositol 3-kinase, Akt, and mammalian target of
      rapamycin is necessary for hypoxia-induced pulmonary artery adventitial
      fibroblast proliferation.
AB  - In contrast to cell types in which exposure to hypoxia causes a general reduction
      of metabolic activity, a remarkable feature of pulmonary artery adventitial
      fibroblasts is their ability to proliferate in response to hypoxia. Previous
      studies have suggested that ERK1/2, phosphatidylinositol 3-kinase (PI3K), Akt,
      and mammalian target of rapamycin (mTOR) are activated by hypoxia and play a role
      in a variety of cell responses. However, the pathways involved in mediating
      hypoxia-induced proliferation are largely unknown. Using pharmacological
      inhibitors, we established that PI3K-Akt, mTOR-p70 ribosomal protein S6 kinase
      (p70S6K), and EKR1/2 signaling pathways play a critical role in hypoxia-induced
      adventitial fibroblast proliferation. We found that exposure of serum-starved
      fibroblasts to 3% O2 resulted in a time-dependent activation of PI3K and
      transient phosphorylation of Akt. However, activation of PI3K was not required
      for activation of ERK1/2, implying a parallel involvement of these pathways in
      the proliferative response of fibroblasts to hypoxia. We found that hypoxia
      induced significant increases in mTOR, p70S6K, 4E-BP1, and S6 ribosomal protein
      phosphorylation, as well as dramatic increases in p70S6K activity. The activation
      of p70S6K/S6 pathway was sensitive to inhibition by rapamycin and LY294002,
      indicating that mTOR and PI3K/Akt are upstream signaling regulators. However, the
      magnitude of hypoxia-induced p70S6K activity and phosphorylation suggests
      involvement of additional signaling pathways. Thus our data demonstrate that
      hypoxia-induced adventitial fibroblast proliferation requires activation and
      interaction of PI3K, Akt, mTOR, p70S6K, and ERK1/2 and provide evidence for
      hypoxic regulation of protein translational pathways in cells exhibiting the
      capability to proliferate under hypoxic conditions.

PMID- 15501928
TI  - Periodic acceleration: effects on vasoactive, fibrinolytic, and coagulation
      factors.
AB  - Cellular and isolated vessel experiments have shown that pulsatile and laminar
      shear stress to the endothelium produces significant release of mediators into
      the circulation. Periodic acceleration (pG(z)) applied to the whole body in the
      direction of the spinal axis adds pulses to the circulation, thereby increasing
      pulsatile and shear stress to the endothelium that should also cause release of
      mediators into the circulation. The purpose of this study was to determine
      whether addition of pulses to the circulation through pG(z) would be sufficient
      to increase shear stress in whole animals and to acutely release mediators and
      how such a physical maneuver might affect coagulation factors. Randomized control
      experiments were performed on anesthetized, supine piglets. The treatment group
      (pG(z)) (n = 12) received pG(z) with a motion platform that moved them
      repetitively head to foot at +/-0.4 g at 180 cpm for 60 min. The control group (n
      = 6) was secured to the platform but remained on conventional ventilation
      throughout the 4-h protocol. Compared with control animals and baseline,
      pulsatile stress produced significant increases of serum nitrite, prostacyclin,
      PGE(2), and tissue plasminogen activator antigen and activity, as well as D
      dimer. There were no significant changes in epinephrine, norepinephrine,
      cortisol, and coagulation factors between groups or from baseline values.
      Pulsatile and laminar shear stress to the endothelium induced by pG(z) safely
      produces increases of vasoactive and fibrinolytic activity. pG(z) has potential
      to achieve mediator-related benefits from the actions of nitric oxide and
      prostaglandins.

PMID- 15501929
TI  - Early fluid retention and severe acute mountain sickness.
AB  - Field studies of acute mountain sickness (AMS) usually include variations in
      exercise, diet, and environmental conditions over days and development of
      clinically apparent edemas. The purpose of this study was to clarify fluid status
      in persons developing AMS vs. those remaining without symptoms during simulated
      altitude with controlled fluid intake, diet, temperature, and without exercise.
      Ninety-nine exposures of 51 men and women to reduced barometric pressure (426
      mmHg = 16,000 ft. = 4,880 m) were carried out for 8-12 h. AMS was evaluated by
      Lake Louise (LL) and AMS-C scores near the end of exposure. Serial measurements
      included fluid balance, electrolyte excretions, and plasma concentrations,
      regulating hormones, and free water clearance. Comparison between 16 subjects
      with the lowest AMS scores near the end of exposure ("non-AMS": mean LL = 1.0,
      range = 0-2.5) and 16 others with the highest AMS scores ("AMS": mean LL = 7.4,
      range = 5-11) demonstrated significant fluid retention in AMS beginning within
      the first 3 h, resulting from reduced urine flow. Plasma Na+ decreased
      significantly after 6 h, indicating dilution throughout the total body water.
      Excretion of Na+ and K+ trended downward with time in both groups, being lower in
      AMS after 6 h, and the urine Na+-to-K+ ratio was significantly higher for AMS
      after 6 h. Renal compensation for respiratory alkalosis, plasma renin activity,
      aldosterone, and atrial natriuretic peptide were not different between groups,
      with the latter tending to rise and aldosterone falling with time of exposure.
      Antidiuretic hormone fell in non-AMS and rose in AMS within 90 min of exposure
      and continued to rise in AMS, closely associated with severity of symptoms and
      fluid retention.

PMID- 15501930
TI  - Farnesyltransferase--new insights into the zinc-coordination sphere paradigm:
      evidence for a carboxylate-shift mechanism.
AB  - Despite the enormous interest that has been devoted to the study of
      farnesyltransferase, many questions concerning its catalytic mechanism remain
      unanswered. In particular, several doubts exist on the structure of the active
      site zinc coordination sphere, more precisely on the nature of the fourth ligand,
      which is displaced during the catalytic reaction by a peptide thiolate. From
      available crystallographic structures, and mainly from x-ray absorption fine
      structure data, two possible alternatives emerge: a tightly zinc-bound water
      molecule or an almost symmetrical bidentate aspartate residue (Asp-297beta). In
      this study, high-level theoretical calculations, with different-sized active site
      models, were used to elucidate this aspect. Our results demonstrate that both
      coordination alternatives lie in a notably close energetic proximity, even though
      the bidentate hypothesis has a somewhat lower energy. The Gibbs reaction and
      activation energies for the mono-bidentate conversion, as well as the structure
      for the corresponding transition state, were also determined. Globally, these
      results indicate that at room temperature the mono-bidentate conversion is
      reversible and very fast, and that probably both states exist in equilibrium,
      which suggests that a carboxylate-shift mechanism may have a key role in the
      farnesylation process by assisting the coordination/displacement of ligands to
      the zinc ion, thereby controlling the enzyme activity. Based on this equilibrium
      hypothesis, an explanation for the existing contradictions between the
      crystallographic and x-ray absorption fine structure results is proposed.

PMID- 15501931
TI  - Mechanical properties of Xenopus egg cytoplasmic extracts.
AB  - Cytoplasmic extracts prepared from Xenopus laevis eggs are used for the
      reconstitution of a wide range of processes in cell biology, and offer a unique
      environment in which to investigate the role of cytoplasmic mechanics without the
      complication of preorganized cellular structures. As a step toward understanding
      the mechanical properties of this system, we have characterized the rheology of
      crude interphase extracts. At macroscopic length scales, the extract forms a soft
      viscoelastic solid. Using a conventional mechanical rheometer, we measure the
      elastic modulus to be in the range of 2-10 Pa, and loss modulus in the range of
      0.5-5 Pa. Using pharmacological and immunological disruption methods, we
      establish that actin filaments and microtubules cooperate to give mechanical
      strength, whereas the intermediate filament cytokeratin does not contribute to
      viscoelasticity. At microscopic length scales smaller than the average network
      mesh size, the response is predominantly viscous. We use multiple particle
      tracking methods to measure the thermal fluctuations of 1 microm embedded tracer
      particles, and measure the viscosity to be approximately 20 mPa-s. We explore the
      impact of rheology on actin-dependent cytoplasmic contraction, and find that
      although microtubules modulate contractile forces in vitro, their interactions
      are not purely mechanical.

PMID- 15501932
TI  - Effects of phenylalanine substitutions in gramicidin A on the kinetics of channel
      formation in vesicles and channel structure in SDS micelles.
AB  - The common occurrence of Trp residues at the aqueous-lipid interface region of
      transmembrane channels is thought to be indicative of its importance for
      insertion and stabilization of the channel in membranes. To further investigate
      the effects of Trp-->Phe substitution on the structure and function of the
      gramicidin channel, four analogs of gramicidin A have been synthesized in which
      the tryptophan residues at positions 9, 11, 13, and 15 are sequentially replaced
      with phenylalanine. The three-dimensional structure of each viable analog has
      been determined using a combination of two-dimensional NMR techniques and
      distance geometry-simulated annealing structure calculations. These phenylalanine
      analogs adopt a homodimer motif, consisting of two beta6.3 helices joined by six
      hydrogen bonds at their NH2-termini. The replacement of the tryptophan residues
      does not have a significant effect on the backbone structure of the channels when
      compared to native gramicidin A, and only small effects are seen on side-chain
      conformations. Single-channel conductance measurements have shown that the
      conductance and lifetime of the channels are significantly affected by the
      replacement of the tryptophan residues (Wallace, 2000; Becker et al., 1991). The
      variation in conductance appears to be caused by the sequential removal of a
      tryptophan dipole, thereby removing the ion-dipole interaction at the channel
      entrance and at the ion binding site. Channel lifetime variations appear to be
      related to changing side chain-lipid interactions. This is supported by data
      relating to transport and incorporation kinetics.

PMID- 15501933
TI  - Phosphatidylethanolamine enhances rhodopsin photoactivation and transducin
      binding in a solid supported lipid bilayer as determined using plasmon-waveguide
      resonance spectroscopy.
AB  - Flash photolysis studies have shown that the membrane lipid environment strongly
      influences the ability of rhodopsin to form the key metarhodopsin II
      intermediate. Here we have used plasmon-waveguide resonance (PWR) spectroscopy,
      an optical method sensitive to both mass and conformation, to probe the effects
      of lipid composition on conformational changes of rhodopsin induced by light and
      due to binding and activation of transducin (G(t)). Octylglucoside-solubilized
      rhodopsin was incorporated by detergent dilution into solid-supported bilayers
      composed either of egg phosphatidylcholine or various mixtures of a nonlamellar
      forming lipid (dioleoylphosphatidylethanolamine; DOPE) together with a lamellar
      forming lipid (dioleoylphosphatidylcholine; DOPC). Light-induced proteolipid
      conformational changes as a function of pH correlated well with previous flash
      photolysis studies, indicating that the PWR spectral shifts monitored
      metarhodopsin II formation. The magnitude of these effects, and hence the extent
      of the conformational transition, was found to be proportional to the DOPE
      content. Our data are consistent with previous suggestions that lipids having a
      negative spontaneous curvature favor elongation of rhodopsin during the
      activation process. In addition, measurements of the G(t)/rhodopsin interaction
      in a DOPC/DOPE (25:75) bilayer at pH 5 demonstrated that light activation
      increased the affinity for G(t) from 64 nM to 0.7 nM, whereas G(t) affinity for
      dark-adapted rhodopsin was unchanged. By contrast, in DOPC bilayers the affinity
      of G(t) for light-activated rhodopsin was only 18 nM at pH 5. Moreover exchange
      of GDP for GTP gamma S was also monitored by PWR spectroscopy. Only the light
      activated receptor was able to induce this exchange which was unaffected by DOPE
      incorporation. These findings demonstrate that nonbilayer-forming lipids can
      alter functionally linked conformational changes of G-protein-coupled receptors
      in membranes, as well as their interactions with downstream effector proteins.

PMID- 15501934
TI  - The elementary mass action rate constants of P-gp transport for a confluent
      monolayer of MDCKII-hMDR1 cells.
AB  - The human multi-drug resistance membrane transporter, P-glycoprotein, or P-gp,
      has been extensively studied due to its importance to human health and disease.
      Thus far, the kinetic analysis of P-gp transport has been limited to steady-state
      Michaelis-Menten approaches or to compartmental models, neither of which can
      prove molecular mechanisms. Determination of the elementary kinetic rate
      constants of transport will be essential to understanding how P-gp works. The
      experimental system we use is a confluent monolayer of MDCKII-hMDR1 cells that
      overexpress P-gp. It is a physiologically relevant model system, and transport is
      measured without biochemical manipulations of P-gp. The Michaelis-Menten mass
      action reaction is used to model P-gp transport. Without imposing the steady
      state assumptions, this reaction depends upon several parameters that must be
      simultaneously fitted. An exhaustive fitting of transport data to find all
      possible parameter vectors that best fit the data was accomplished with a
      reasonable computation time using a hierarchical algorithm. For three P-gp
      substrates (amprenavir, loperamide, and quinidine), we have successfully fitted
      the elementary rate constants, i.e., drug association to P-gp from the apical
      membrane inner monolayer, drug dissociation back into the apical membrane inner
      monolayer, and drug efflux from P-gp into the apical chamber, as well as the
      density of efflux active P-gp. All three drugs had overlapping ranges for the
      efflux active P-gp, which was a benchmark for the validity of the fitting
      process. One novel finding was that the association to P-gp appears to be rate
      limited solely by drug lateral diffusion within the inner monolayer of the plasma
      membrane for all three drugs. This would be expected if P-gp structure were open
      to the lipids of the apical membrane inner monolayer, as has been suggested by
      recent structural studies. The fitted kinetic parameters show how P-gp efflux of
      a wide range of xenobiotics has been maximized.

PMID- 15501935
TI  - Interaction forces and morphology of a protein-resistant poly(ethylene glycol)
      layer.
AB  - The molecular interactions on a protein-resistant surface coated with low
      molecular-weight poly(ethylene glycol) (PEG) copolymer brushes are investigated
      using the extended surface forces apparatus. The observed interaction force is
      predominantly repulsive and nearly elastic. The chains are extended with respect
      to the Flory radius, which is in agreement with qualitative predictions of
      scaling theory. Comparison with theory allows the determination of relevant
      quantities such as brush length and adsorbed mass. Based on these results, we
      propose a molecular model for the adsorbed copolymer morphology. Surface-force
      isotherms measured at high resolution allow distinctive structural forces to be
      detected, suggesting the existence of a weak equilibrium network between
      poly(ethylene glycol) and water--a finding in accordance with the remarkable
      solution properties of PEG. The occurrence of a fine structure is interpreted as
      a water-induced restriction of the polymer's conformational space. This
      restriction is highly relevant for the phenomenon of PEG protein resistance.
      Protein adsorption requires conformational transitions, both in the protein as
      well as in the PEG layer, which are energetically and kinetically unfavorable.

PMID- 15501936
TI  - Knowledge-based elastic potentials for docking drugs or proteins with nucleic
      acids.
AB  - Elastic ellipsoidal functions defined by the observed hydration patterns around
      the DNA bases provide a new basis for measuring the recognition of ligands in the
      grooves of double-helical structures. Here a set of knowledge-based potentials
      suitable for quantitative description of such behavior is extracted from the
      observed positions of water molecules and amino acid atoms that form hydrogen
      bonds with the nitrogenous bases in high resolution crystal structures. Energies
      based on the displacement of hydrogen-bonding sites on drugs in DNA-crystal
      complexes relative to the preferred locations of water binding around the
      heterocyclic bases are low, pointing to the reliability of the potentials and the
      apparent displacement of water molecules by drug atoms in these structures. The
      validity of the energy functions has been further examined in a series of
      sequence substitution studies based on the structures of DNA bound to polyamides
      that have been designed to recognize the minor-groove edges of Watson-Crick
      basepairs. The higher energies of binding to incorrect sequences superimposed
      (without conformational adjustment or displacement of polyamide ligands) on
      observed high resolution structures confirm the hypothesis that the drug subunits
      associate with specific DNA bases. The knowledge-based functions also account
      satisfactorily for the measured free energies of DNA-polyamide association in
      solution and the observed sites of polyamide binding on nucleosomal DNA. The
      computations are generally consistent with mechanisms by which minor-groove
      binding ligands are thought to recognize DNA basepairs. The calculations suggest
      that the asymmetric distributions of hydrogen-bond-forming atoms on the minor
      groove edge of the basepairs may underlie ligand discrimination of G.C from C.G
      pairs, in addition to the commonly believed role of steric hindrance. The
      analysis of polyamide-bound nucleosomal structures reveals other discrepancies in
      the expected chemical design, including unexpected contacts to DNA and modified
      basepair targets of some ligands. The ellipsoidal potentials thus appear
      promising as a mathematical tool for the study of drug- and protein-DNA
      interactions and for gaining new insights into DNA-binding mechanisms.

PMID- 15501937
TI  - Diffusion in two-component lipid membranes--a fluorescence correlation
      spectroscopy and monte carlo simulation study.
AB  - Using fluorescence correlation spectroscopy, calorimetry, and Monte Carlo
      simulations, we studied diffusion processes in two-component membranes close to
      the chain melting transition. The aim is to describe complex diffusion behavior
      in lipid systems in which gel and fluid domains coexist. Diffusion processes in
      gel membranes are significantly slower than in fluid membranes. Diffusion
      processes in mixed phase regions are therefore expected to be complex. Due to
      statistical fluctuations the gel-fluid domain patterns are not uniform in space
      and time. No models for such diffusion processes are available. In this article,
      which is both experimental and theoretical, we investigated the diffusion in DMPC
      DSPC lipid mixtures as a function of temperature and composition. We then modeled
      the fluorescence correlation spectroscopy experiment using Monte Carlo
      simulations to analyze the diffusion process. It is shown that the simulations
      yield a very good description of the experimental diffusion processes, and that
      predicted autocorrelation profiles are superimposable with the experimental
      curves. We believe that this study adds to the discussion on the physical nature
      of rafts found in biomembranes.

PMID- 15501938
TI  - Frequency encoding of T-cell receptor engagement dynamics in calcium time series.
AB  - The sustained increase of the cytosolic calcium concentration ([Ca2+]i) plays a
      central role in T-cell receptor (TCR)-mediated T-cell activation. Previous
      experiments using a [Ca2+]i clamp technique have demonstrated that specificity is
      encoded by the [Ca2+]i oscillation frequency since cytokine transcription factors
      are activated in a frequency-dependent manner. An outstanding question is how
      encoding of specific activation occurs under physiological conditions. In this
      case, continuous TCR interactions with specific peptides bound to cell surface
      associated major histocompatibility complexes are driving the sustained [Ca2+]i
      increase. Addressing this question, we analyzed [Ca2+]i time series from
      individual T-cells mathematically. We are able to identify signal fluctuations
      associated with the TCR-triggering dynamics. We also find that [Ca2+]i time
      series associated with T-cells activated to IFN-gamma production exhibit
      oscillations with higher frequencies than the time series corresponding to T
      cells not activated to IFN-gamma production. We show that signal autocorrelations
      are a means to distinguish functional signals according to their associated
      cytokine production. The signal level, however, allows for the distinction of
      nonfunctional from functional signals. These findings provide strong evidence for
      specificity encoding of biological functions in intracellular signals via signal
      level and signal correlations.

PMID- 15501939
TI  - Protein folding in high-dimensional spaces: hypergutters and the role of
      nonnative interactions.
AB  - We explore the consequences of very high dimensionality in the dynamical
      landscape of protein folding. Consideration of both typical range of stabilizing
      interactions, and folding rates themselves, leads to a model of the energy
      hypersurface that is characterized by the structure of diffusive "hypergutters"
      as well as the familiar "funnels". Several general predictions result: 1),
      intermediate subspaces of configurations will always be visited; 2), specific but
      nonnative interactions may be important in stabilizing these low-dimensional
      diffusive searches on the folding pathway, as well as native interactions; 3),
      sequential barriers will commonly be found, even in "two-state" proteins; 4),
      very early times will show characteristic departures from single-exponential
      kinetics; and 5), contributions of nonnative interactions to Phi-values and
      "Chevron plots" are calculable, and may be significant. The example of a three
      helix bundle is treated in more detail as an illustration. The model also shows
      that high-dimensional structures provide conceptual relations between different
      models of protein folding. It suggests that kinetic strategies for fast folding
      may be encoded rather generally in nonnative as well as in native interactions.
      The predictions are related to very recent findings in experiment and simulation.

PMID- 15501940
TI  - The high-resolution architecture and structural dynamics of Bacillus spores.
AB  - The capability to image single microbial cell surfaces at nanometer scale under
      native conditions would profoundly impact mechanistic and structural studies of
      pathogenesis, immunobiology, environmental resistance, and biotransformation.
      Here, using in vitro atomic force microscopy, we have directly visualized high
      resolution native structures of bacterial endospores, including the exosporium
      and spore coats of four Bacillus species in air and water environments. Our
      results demonstrate that the mechanisms of spore coat self-assembly are similar
      to those described for inorganic and macromolecular crystallization. The
      dimensions of individual Bacillus atrophaeus spores decrease reversibly by 12% in
      response to a change in the environment from fully hydrated to air-dried state,
      establishing that the dormant spore is a dynamic physical structure. The
      interspecies distributions of spore length and width were determined for four
      species of Bacillus spores in water and air environments. The dimensions of
      individual spores differ significantly depending upon species, growth regimes,
      and environmental conditions. These findings may be useful in the reconstruction
      of environmental and physiological conditions during spore formation and for
      modeling the inhalation and dispersal of spores. This study provides a direct
      insight into molecular architecture and structural variability of bacterial
      endospores as a function of spatial and developmental organizational scales.

PMID- 15501941
TI  - Investigation of ligand binding to the multidrug resistance protein EmrE by
      isothermal titration calorimetry.
AB  - Escherichia coli multidrug resistance protein E (EmrE) is an integral membrane
      protein spanning the inner membrane of Escherichia coli that is responsible for
      this organism's resistance to a variety of lipophilic cations such as quaternary
      ammonium compounds (QACs) and interchelating dyes. EmrE is a 12-kDa protein of
      four transmembrane helices considered to be functional as a multimer. It is an
      efflux transporter that can bind and transport cytoplasmic QACs into the
      periplasm using the energy of the proton gradient across the inner membrane.
      Isothermal titration calorimetry provides information about the stoichiometry and
      thermodynamic properties of protein-ligand interactions, and can be used to
      monitor the binding of QACs to EmrE in different membrane mimetic environments.
      In this study the ligand binding to EmrE solubilized in dodecyl maltoside, sodium
      dodecyl sulfate and reconstituted into small unilamellar vesicles is examined by
      isothermal titration calorimetry. The binding stoichiometry of EmrE to drug was
      found to be 1:1, demonstrating that oligomerization of EmrE is not necessary for
      binding to drug. The binding of EmrE to drug was observed with the dissociation
      constant (K(D)) in the micromolar range for each of the drugs in any of the
      membrane mimetic environments. Thermodynamic properties demonstrated this
      interaction to be enthalpy-driven with similar enthalpies of 8-12 kcal/mol for
      each of the drugs in any of the membrane mimetics.

PMID- 15501942
TI  - Monte Carlo simulation for single RNA unfolding by force.
AB  - Using polymer elastic theory and known RNA free energies, we construct a Monte
      Carlo algorithm to simulate the single RNA folding and unfolding by mechanical
      force on the secondary structure level. For the constant force ensemble, we
      simulate the force-extension curves of the P5ab, P5abc deltaA, and P5abc
      molecules in equilibrium. For the constant extension ensemble, we focus on the
      mechanical behaviors of the RNA P5ab molecule, which include the unfolding force
      dependence on the pulling speed, the force-hysteresis phenomenon, and the
      coincidence of stretching-relaxing force-curves in thermal equilibrium. We
      particularly simulate the time traces of the end-to-end distance of the P5ab
      under the constant force in equilibrium, which also have been recorded in the
      recent experiment. The reaction rate constants for the folding and unfolding are
      calculated. Our results show that the agreement between the simulation and the
      experimental measurements is satisfactory.

PMID- 15501943
TI  - Quantitative imaging of lymphocyte membrane protein reorganization and signaling.
AB  - Changes in membrane protein localization are critical to establishing cell
      polarity and regulating cell signaling. Fluorescence microscopy of labeled
      proteins allows visualization of these changes, but quantitative analysis is
      needed to study this aspect of cell signaling in full mechanistic detail. We have
      developed a novel approach for quantitative assessment of membrane protein
      redistribution based on four-dimensional video microscopy of fluorescently
      labeled proteins. Our analytic system provides robust automated methods for cell
      surface reconstruction, cell shape tracking, cell-surface distance measurement,
      and cluster formation analysis. These methods permit statistical analyses and
      testing of mechanistic hypotheses regarding cell signaling. We have used this
      approach to measure antigen-dependent clustering of signaling molecules in CD4+ T
      lymphocytes, obtaining clustering velocities consistent with single-particle
      tracking data. Our system captures quantitative differences in clustering between
      signaling proteins with distinct biological functions. Our methods can be
      generalized to a range of cell-signaling phenomena and enable novel applications
      not feasible with single-particle studies, such as analysis of subcellular
      protein localization in live organ culture.

PMID- 15501944
TI  - Fluorescence spectroscopy of conformational changes of single LH2 complexes.
AB  - We have investigated the energy landscape of the bacterial photosynthetic
      peripheral light-harvesting complex LH2 of purple bacterium Rhodopseudomonas
      acidophila by monitoring sequences of fluorescence spectra of single LH2
      assemblies, at room temperature, with different excitation intensities as well as
      at elevated temperatures, utilizing a confocal microscope. The fluorescence peak
      wavelength of individual LH2 complexes was found to abruptly move between long
      lived quasi-stable levels differing by up to 30 nm. The frequency and size of
      these fluorescence peak movements were found to increase linearly with the
      excitation intensity. These spectral shifts either to the blue or to the red were
      accompanied by a broadening and decrease of the intensity of the fluorescence
      spectrum. The probability for a particle to undergo significant spectral shift in
      either direction was found to be roughly the same. Using the modified Redfield
      theory, the observed changes in spectral shape and intensity were accounted for
      by changes in the realization of the static disorder. Long lifetimes of the quasi
      stable states suggest large energetic barriers between the states characterized
      by different emission spectra.

PMID- 15501945
TI  - FPL 64176 modification of Ca(V)1.2 L-type calcium channels: dissociation of
      effects on ionic current and gating current.
AB  - FPL 64176 (FPL) is a nondihydropyridine compound that dramatically increases
      macroscopic inward current through L-type calcium channels and slows activation
      and deactivation. To understand the mechanism by which channel behavior is
      altered, we compared the effects of the drug on the kinetics and voltage
      dependence of ionic currents and gating currents. Currents from a homogeneous
      population of channels were obtained using cloned rabbit Ca(V)1.2 (alpha1C,
      cardiac L-type) channels stably expressed in baby hamster kidney cells together
      with beta1a and alpha2delta1 subunits. We found a striking dissociation between
      effects of FPL on ionic currents, which were modified strongly, and on gating
      currents, which were not detectably altered. Inward ionic currents were enhanced
      approximately 5-fold for a voltage step from -90 mV to +10 mV. Kinetics of
      activation and deactivation were slowed dramatically at most voltages. Curiously,
      however, at very hyperpolarized voltages (< -250 mV), deactivation was actually
      faster in FPL than in control. Gating currents were measured using a variety of
      inorganic ions to block ionic current and also without blockers, by recording
      gating current at the reversal potential for ionic current (+50 mV). Despite the
      slowed kinetics of ionic currents, FPL had no discernible effect on the
      fundamental movements of gating charge that drive channel gating. Instead, FPL
      somehow affects the coupling of charge movement to opening and closing of the
      pore. An intriguing possibility is that the drug causes an inactivated state to
      become conducting without otherwise affecting gating transitions.

PMID- 15501946
TI  - The role of stochastic and modal gating of cardiac L-type Ca2+ channels on early
      after-depolarizations.
AB  - Certain signaling events that promote L-type Ca2+ channel (LCC) phosphorylation,
      such as beta-adrenergic stimulation or an increased expression of
      Ca(2+)/calmodulin-dependent protein kinase II, promote mode 2 gating of LCCs.
      Experimental data suggest the hypothesis that these events increase the
      likelihood of early after-depolarizations (EADs). We test this hypothesis using
      an ionic model of the canine ventricular myocyte incorporating stochastic gating
      of LCCs and ryanodine-sensitive calcium release channels. The model is extended
      to describe myocyte responses to the beta-adrenergic agonist isoproterenol.
      Results demonstrate that in the presence of isoproterenol the random opening of a
      small number of LCCs gating in mode 2 during the plateau phase of the action
      potential (AP) can trigger EADs. EADs occur randomly, where the likelihood of
      these events increases as a function of the fraction of LCCs gating in mode 2.
      Fluctuations of the L-type Ca2+ current during the AP plateau lead to variability
      in AP duration. Consequently, prolonged APs are occasionally observed and exhibit
      an increased likelihood of EAD formation. These results suggest a novel
      stochastic mechanism, whereby phosphorylation-induced changes in LCC gating
      properties contribute to EAD generation.

PMID- 15501947
TI  - Near-critical behavior of aminoacyl-tRNA pools in E. coli at rate-limiting supply
      of amino acids.
AB  - The rates of consumption of different amino acids in protein synthesis are in
      general stoichiometrically coupled with coefficients determined by codon usage
      frequencies on translating ribosomes. We show that when the rates of synthesis of
      two or more amino acids are limiting for protein synthesis and exactly matching
      their coupled rates of consumption on translating ribosomes, the pools of
      aminoacyl-tRNAs in ternary complex with elongation factor Tu and GTP are
      hypersensitive to a variation in the rate of amino acid supply. This high
      sensitivity makes a macroscopic analysis inconclusive, because it is accompanied
      by almost free and anticorrelated diffusion in copy numbers of ternary complexes.
      This near-critical behavior is relevant for balanced growth of Escherichia coli
      cells in media that lack amino acids and for adaptation of E. coli cells after
      downshifts from amino-acid-containing to amino-acid-lacking growth media. The
      theoretical results are used to discuss transcriptional control of amino acid
      synthesis during multiple amino acid limitation, the recovery of E. coli cells
      after nutritional downshifts and to propose a robust mechanism for the regulation
      of RelA-dependent synthesis of the global effector molecule ppGpp.

PMID- 15501948
TI  - Comparing folding codes in simple heteropolymer models of protein evolutionary
      landscape: robustness of the superfunnel paradigm.
AB  - Understanding the evolution of biopolymers is a key element in rationalizing
      their structures and functions. Simple exact models (SEMs) are well-positioned to
      address general principles of evolution as they permit the exhaustive enumeration
      of both sequence and structure (conformational) spaces. The physics-based models
      of the complete mapping between genotypes and phenotypes afforded by SEMs have
      proven valuable for gaining insight into how adaptation and selection operate
      among large collections of sequences and structures. This study compares the
      properties of evolutionary landscapes of a variety of SEMs to delineate robust
      predictions and possible model-specific artifacts. Among the models studied, the
      ruggedness of evolutionary landscape is significantly model-dependent; those
      derived from more protein-like models appear to be smoother. We found that a
      common practice of restricting protein structure space to maximally compact
      lattice conformations results in (i.e., "designs in") many encodable (designable)
      structures that are not otherwise encodable in the corresponding unrestrained
      structure space. This discrepancy is especially severe for model potentials that
      seek to mimic the major role of hydrophobic interactions in protein folding. In
      general, restricting conformations to be maximally compact leads to larger
      changes in the model genotype-phenotype mapping than a moderate shifting of
      reference state energy of the model potential function to allow for more specific
      encoding via the "designing out" effects of repulsive interactions. Despite these
      variations, the superfunnel paradigm applies to all SEMs we have tested: For a
      majority of neutral nets across different models, there exists a funnel-like
      organization of native stabilities for the sequences in a neutral net encoding
      for the same structure, and the thermodynamically most stable sequence is also
      the most robust against mutation.

PMID- 15501950
TI  - Naturally derived commercial surfactants differ in composition of surfactant
      lipids and in surface viscosity.
AB  - Pulmonary surfactant biophysical properties are best described by surface tension
      and surface viscosity. Besides lecithin, surfactant contains a variety of minor
      lipids, such as plasmalogens, polyunsaturated fatty acid-containing phospholipids
      (PUFA-PL), and cholesterol. Plasmalogens and cholesterol improve surface
      properties of lipid mixtures significantly. High PUFA-PL and plasmalogen content
      in tracheal aspirate of preterm infants reduces the risk of developing chronic
      lung disease. Different preparations are available for exogenous surfactant
      substitution; however, little is known about lipid composition and surface
      viscosity. Thus lipid composition and surface properties (measured by oscillating
      drop surfactometer) of three commercial surfactant preparations (Alveofact,
      Curosurf, Survanta) were compared. Lipid composition exhibited strong
      differences: Survanta had the highest proportion of disaturated PL and total
      neutral lipids and the lowest proportion of PUFA-PL. Highest plasmalogen and PUFA
      PL concentrations were found in Curosurf (3.8 +/- 0.1 vs. 26 +/- 1 mol%) compared
      with Alveofact (0.9 +/- 0.3 vs. 11 +/- 1) and Survanta (1.5 +/- 0.2 vs. 6 +/- 1).
      In Survanta samples, viscosity increased >8 x 10(-6) kg/s at surface tension of
      30 mN/m. Curosurf showed only slightly increased surface viscosity below surface
      tensions of 25 mN/m, and viscosity did not reach 5 x 10(-6) kg/s. By adding
      defined PL to Survanta, we obtained a Curosurf-like lipid mixture (without
      plasmalogens) that exhibited biophysical properties like Curosurf. Different
      lipid compositions could explain some of the differences in surface viscosity.
      Therefore, PL pattern and minor surfactant lipids are important for biophysical
      activity and should be considered when designing synthetic surfactant
      preparations.

PMID- 15501949
TI  - Mitochondrial Ca2+ dynamics reveals limited intramitochondrial Ca2+ diffusion.
AB  - To reveal heterogeneity of mitochondrial function on the single-mitochondrion
      level we have studied the spatiotemporal dynamics of the mitochondrial Ca2+
      signaling and the mitochondrial membrane potential using wide-field fluorescence
      imaging and digital image processing techniques. Here we demonstrate first-time
      discrete sites--intramitochondrial hotspots--of Ca2+ uptake after Ca2+ release
      from intracellular stores, and spreading of Ca2+ rise within the mitochondria.
      The phenomenon was characterized by comparison of observations in intact cells
      stimulated by ATP and in plasma membrane permeabilized or in ionophore-treated
      cells exposed to elevated buffer [Ca2+]. The findings indicate that Ca2+ diffuses
      laterally within the mitochondria, and that the diffusion is limited for shorter
      segments of the mitochondrial network. These observations were supported by
      mathematical simulation of buffered diffusion. The mitochondrial membrane
      potential was investigated using the potentiometric dye TMRM. Irradiation-induced
      fluctuations (flickering) of TMRM fluorescence showed synchronicity over large
      regions of the mitochondrial network, indicating that certain parts of this
      network form electrical syncytia. The spatial extension of these syncytia was
      decreased by 2-aminoethoxydiphenyl borate (2-APB) or by propranolol (blockers of
      nonclassical mitochondrial permeabilities). Our data suggest that mitochondria
      form syncytia of electrical conductance whereas the passage of Ca2+ is restricted
      to the individual organelle.

PMID- 15501951
TI  - Evaluating the efficiency of targeted designs for randomized clinical trials.
AB  - PURPOSE: Genomic technologies make it increasingly possible to identify patients
      most likely to benefit from a molecularly targeted drug. This creates the
      opportunity to conduct targeted clinical trials with eligibility restricted to
      patients predicted to be responsive to the drug. EXPERIMENTAL DESIGN: We
      evaluated the relative efficiency of a targeted clinical trial design to an
      untargeted design for a randomized clinical trial comparing a new treatment to a
      control. Efficiency was evaluated with regard to number of patients required for
      randomization and number required for screening. RESULTS: The effectiveness of
      this design, relative to the more traditional design with broader eligibility,
      depends on multiple factors, including the proportion of responsive patients, the
      accuracy of the assay for predicting responsiveness, and the degree to which the
      mechanism of action of the drug is understood. Explicit formulas were derived for
      computing the relative efficiency of targeted versus untargeted designs.
      CONCLUSIONS: Targeted clinical trials can dramatically reduce the number of
      patients required for study in cases where the mechanism of action of the drug is
      understood and an accurate assay for responsiveness is available.

PMID- 15501952
TI  - A phase II trial of neoadjuvant docetaxel and capecitabine for locally advanced
      breast cancer.
AB  - PURPOSE: This study evaluated the toxicity and efficacy of docetaxel/capecitabine
      as neoadjuvant treatment for stage 2/3 breast cancer. EXPERIMENTAL DESIGN:
      Subjects with newly diagnosed invasive stage 2 and 3 breast cancer were eligible.
      The first cohort of patients was treated at dose A with neoadjuvant docetaxel (75
      mg/m(2) i.v. day 1) and capecitabine (1000 mg/m(2) orally twice daily days 2-15)
      for four cycles. A second cohort of subjects was treated with a reduced dose,
      dose B, of docetaxel (60 mg/m(2) i.v. day 1) and capecitabine (937.5 mg/m(2)
      orally twice daily days 2-15). RESULTS: Thirty patients were enrolled. Eight of
      10 patients treated at dose A required dose reductions of either docetaxel or
      capecitabine secondary to grade 3 or 4 toxicities: mucositis (1), hand-foot
      syndrome (3), diarrhea (2), perirectal abscess (1), and neutropenia (2). Because
      of a high rate of dose reductions, the next 20 patients were treated at dose B.
      The mean cumulative administered dose of docetaxel was 285 and 231 mg/m(2) at
      dose A and dose B, respectively. For capecitabine, the mean cumulative dose at
      dose A and B were similar at 1585 and 1627 mg/m(2)/day, respectively. The overall
      clinical response rate was 90% with 31% of patients having a complete response
      and 59% having a partial response. A pathological complete response in the breast
      was achieved in 10% of patients after four cycles of docetaxel/capecitabine.
      CONCLUSIONS: Docetaxel/capecitabine is a highly active regimen in the neoadjuvant
      setting. Neoadjuvant therapy with 75 mg/m(2) docetaxel and 1600 mg/m(2)/day days
      2-15 is recommended.

PMID- 15501953
TI  - Clinical and biomarker correlates of androgen-independent, locally aggressive
      prostate cancer with limited metastatic potential.
AB  - PURPOSE: We have identified a subset of patients exhibiting extended survival
      with metastases from androgenindependent prostate cancer of which the principal
      site of progression was the tumor primary. The purpose of this study was to
      evaluate the expression of selected biomarkers to characterize this subset of
      prostate cancer patients. EXPERIMENTAL DESIGN: A 105 core tissue microarray was
      constructed from primary tumor samples from 16 patients, with matched lymph node
      metastases in 5 cases. Immunohistochemistry was used to evaluate selected
      biomarkers associated with prostate cancer progression. Standard statistical
      methodologies were used to compute the distribution of time to progression and
      overall survival associations between pairs of biomarkers. Hierarchical
      clustering was done between groups of biomarkers, and we devised new methods to
      assess homogeneity of biomarker expression. RESULTS: The median interval from
      diagnosis to salvage surgery was 65 months. The profile of biomarker expression
      was notable for virtual absence of neuroendocrine features, high CD10, low matrix
      metalloproteinase (MMP)-9, high E-cadherin expression, and high membranous beta
      catenin. The mean proliferative index was 12.1 +/- 10.1%, and the mean apoptotic
      index was 3.48 +/- 2.22%, and there was a significant correlation between these
      indices. Expression of the epidermal growth factor receptor was associated with
      phospho-AKT and proliferative index but inversely associated with phospho-STAT3.
      CONCLUSIONS: The cohort of prostate cancer patients, characterized by locally
      aggressive disease rather than lethal metastatic progression, was associated with
      a distinctive biomarker signature. The biomarker profile was, in general, more
      consistent with low-grade prostate cancer exhibiting local growth rather than
      metastatic progression. Ongoing studies will establish whether this unique subset
      of patients can be identified prospectively.

PMID- 15501954
TI  - Activation of the Akt/mammalian target of rapamycin/4E-BP1 pathway by ErbB2
      overexpression predicts tumor progression in breast cancers.
AB  - The Akt/mammalian target of rapamycin (mTOR)/4E-BP1 pathway is considered to be a
      central regulator of protein synthesis, involving the regulation of cell
      proliferation, differentiation, and survival. The inhibitors of mTOR as
      anticancer reagents are undergoing active evaluation in various malignancies
      including breast cancer. However, the activation status of the Akt/mTOR/4E-BP1
      pathway and its potential roles in breast cancers remain unknown. Thus, we
      examined 165 invasive breast cancers with specific antibodies for the
      phosphorylation of Akt, mTOR, and 4E-BP1 by immunohistochemistry and compared
      them with normal breast epithelium, fibroadenoma, intraductal hyperplasia, and
      ductal carcinoma in situ. We discovered that the phosphorylation of Akt, mTOR,
      and 4E-BP1 increased progressively from normal breast epithelium to hyperplasia
      and abnormal hyperplasia to tumor invasion. Phosphorylated Akt, mTOR, and 4E-BP1
      were positively associated with ErbB2 overexpression. Survival analysis showed
      that phosphorylation of each of these three markers was associated with poor
      disease-free survival independently. In vitro, we further confirmed the causal
      relationship between ErbB2 overexpression and mTOR activation, which was
      associated with enhanced invasive ability and sensitivity to a mTOR inhibitor,
      rapamycin. Our results, for the first time, demonstrate the following: (a) high
      levels of phosphorylation of Akt, mTOR, and 4E-BP1 in breast cancers, indicating
      activation of the Akt/mTOR/4E-BP1 pathway in breast cancer development and
      progression; (b) a link between ErbB2 and the Akt/mTOR/4E-BP1 pathway in breast
      cancers in vitro and in vivo, indicating the possible role of Akt/mTOR activation
      in ErbB2-mediated breast cancer progression; and (c) a potential role for this
      pathway in predicting the prognosis of patients with breast cancer, especially
      those treated with mTOR inhibitors.

PMID- 15501955
TI  - Molecular profiling of inflammatory breast cancer: identification of a poor
      prognosis gene expression signature.
AB  - PURPOSE: Inflammatory breast cancer (IBC) is a rare but particularly aggressive
      form of primary breast cancer. The molecular mechanisms responsible for IBC are
      largely unknown. EXPERIMENTAL DESIGN: To obtain further insight into the
      molecular pathogenesis of IBC, we used real-time quantitative reverse
      transcription (RT)-PCR to quantify the mRNA expression of 538 selected genes in
      IBC relative to non-IBC. RESULTS: Twenty-seven (5.0%) of the 538 genes were
      significantly up-regulated in IBC compared with non-IBC. None were down
      regulated. The 27 up-regulated genes mainly encoded transcription factors (JUN,
      EGR1, JUNB, FOS, FOSB, MYCN, and SNAIL1), growth factors (VEGF, DTR/HB-EGF,
      IGFBP7, IL6, ANGPT2, EREG, CCL3/MIP1A, and CCL5/RANTES) and growth factor
      receptors (TBXA2R, TNFRSF10A/TRAILR1, and ROBO2). We also identified a gene
      expression profile, based on MYCN, EREG, and SHH, which discriminated subgroups
      of IBC patients with good, intermediate, and poor outcome. CONCLUSION: Our study
      has identified a limited number of signaling pathways that require inappropriate
      activation for IBC development. Some of the up-regulated genes identified here
      could offer useful diagnostic or prognostic markers and could form the basis of
      novel therapeutic strategies.

PMID- 15501956
TI  - Variability in the degree of expression of phosphorylated IkappaBalpha in chronic
      lymphocytic leukemia cases with nodal involvement.
AB  - PURPOSE: Based on previous preliminary observations, we hypothesize that the
      molecular and clinical variability of chronic lymphocytic leukemia (CLL) reflects
      differences in the degree of nuclear factor (NF)-kappaB activation, as determined
      by the expression of phosphorylated IkappaBalpha (p-IkappaBalpha). EXPERIMENTAL
      DESIGN: The expression profile (mRNA and protein expression) was analyzed with
      the Centro Nacional de Investigaciones Oncologicas Oncochip, a cDNA microarray
      containing 6386 cancer-related genes, and a tissue microarray (TMA). The results
      were correlated with the IgV(H) mutational status, ZAP-70 expression, cytogenetic
      alterations, and clinical outcome. RESULTS: We found correlations between the
      presence of p-IkappaBalpha, a surrogate marker of NF-kappaB activation, and
      changes in the expression profile (mRNA and protein expression) and clinical
      outcome in a series of CLL cases with lymph node involvement. Activation of NF
      kappaB, as determined by the expression of p-IkappaBalpha, was associated with
      the expression of a set of genes comprising key genes involved in the control of
      B-cell receptor signaling, signal transduction, and apoptosis, including SYK,
      LYN, BCL2, CCR7, BTK, PIK3CD, and others. Cases with increased expression of p
      IkappaBalpha showed longer overall survival than cases with lower expression. A
      Cox regression model was derived to estimate some parameters of prognostic
      interest: IgV(H) mutational status, ZAP-70, and p-IkappaBalpha expression. The
      multivariate analysis disclosed p-IkappaBalpha and ZAP-70 expression as
      independent prognostic factors of survival. CONCLUSIONS: A variable degree of
      activation of NF-kappaB, as determined by the expression of p-IkappaBalpha, is an
      identifiable event in CLL, and is correlated with changes in the expression
      profile and overall survival.

PMID- 15501957
TI  - Components of the cell death machine and drug sensitivity of the National Cancer
      Institute Cell Line Panel.
AB  - PURPOSE: According to some studies, susceptibility of cells to anticancer drug
      induced apoptosis is markedly inhibited by targeted deletion of genes encoding
      apoptotic protease activating factor 1 (Apaf-1) or certain caspases. Information
      about levels of these polypeptides in common cancer cell types and any possible
      correlation with drug sensitivity in the absence of gene deletion is currently
      fragmentary. EXPERIMENTAL DESIGN: Immunoblotting was used to estimate levels of
      Apaf-1 as well as procaspase-2, -3, -6, -7, -8, and -9 in the 60-cell-line panel
      used for drug screening by the National Cancer Institute. Sensitivity of the same
      lines to >80,000 compounds was determined with 48-hour sulforhodamine B binding
      assays. Additional 6-day assays were performed for selected agents. RESULTS:
      Levels of Apaf-1 and procaspases varied widely. Apaf-1 and procaspase-9, which
      are implicated in caspase activation after treatment of cells with various
      anticancer drugs, were detectable in all of the cell lines, with levels of Apaf-1
      ranging from approximately 1 x 10(5) to 2 x 10(6) molecules per cell and
      procaspase-9 from approximately 5 x 10(3) to approximately 1.6 x 10(5) molecules
      per cell. Procaspase-8 levels ranged from 1.7 x 10(5) to 8 x 10(6) molecules per
      cell. Procaspase-3, a major effector caspase, varied from undetectable to
      approximately 1.6 x 10(6) molecules per cell. Correlations between levels of
      these polypeptides and sensitivity to any of a variety of experimental or
      conventional antineoplastic agents in either 2-day or 6-day cytotoxicity assays
      were weak at best. CONCLUSIONS: With the exception of caspase-3, all of the
      components of the core cell-death machinery are expressed in all of the cell
      lines examined. Despite variations in expression, levels of any one component are
      not a major determinant of drug sensitivity in these cells in vitro.

PMID- 15501958
TI  - Induction of thyroid cancer cell apoptosis by a novel nuclear factor kappaB
      inhibitor, dehydroxymethylepoxyquinomicin.
AB  - PURPOSE: The objective of the study was to determine the effects of a novel
      selective nuclear factor kappaB (NF-kappaB) inhibitor,
      dehydroxymethylepoxyquinomicin (DHMEQ), in thyroid carcinoma cells in vitro and
      in vivo and to additionally elucidate the molecular mechanisms underlying the
      action of this chemotherapeutic agent. EXPERIMENTAL DESIGN: In the in vitro
      experiments, the induction of apoptosis by DHMEQ in various human thyroid
      carcinoma cell types was determined by flow cytometry analysis of annexin-V
      binding and the caspase activation by Western blotting. For the in vivo study,
      female nu/nu mice were xenografted with s.c. FRO thyroid tumors. DHMEQ solution
      was injected i.p. at a dose of 8 mg/kg/day for two weeks. Tumor dimensions were
      monitored twice weekly, and apoptosis in tumor specimens was determined by
      terminal deoxynucleotidyl transferase-mediated nick end labeling staining.
      RESULTS: Treatment with DHMEQ substantially inhibited the translocation of p65
      and p50 NF-kappaB subunits to the nucleus, the DNA-binding activity of the
      RelA/p65, NF-kappaB-dependent expression of the inhibitor of apoptosis (IAP)
      family proteins, cIAP-1, cIAP-2, and XIAP, and the de novo synthesis of inhibitor
      of nuclear factor kappaB alpha. At concentration levels ranging from 0.1 to 5
      microg/ml, DHMEQ induced a caspase-mediated apoptotic response that could be
      abrogated by the c-Jun NH(2)-terminal kinase inhibitor SP600125 but not by either
      mitogen-activated protein/extracellular signal-regulated kinase kinase or p38
      inhibitors. In contrast, normal human thyrocytes were resistant to DHMEQ-induced
      apoptosis. At higher doses of DHMEQ we observed the necrotic-like killing of both
      normal and malignant thyrocytes, which was resistant to mitogen-activated protein
      kinase inhibitors. In nude mice DHMEQ substantially inhibited tumor growth
      without observable side effects, and increased numbers of apoptotic cells were
      observed in the histologic sections of tumors treated with DHMEQ. CONCLUSIONS:
      Our results show the potential usefulness of the novel NF-kappaB inhibitor,
      DHMEQ, in future therapeutic strategies for the treatment of thyroid cancers that
      do not respond to conventional approaches.

PMID- 15501959
TI  - A phase I and pharmacodynamic study of fludarabine, carboplatin, and topotecan in
      patients with relapsed, refractory, or high-risk acute leukemia.
AB  - PURPOSE: A novel regimen designed to maximize antileukemia activity of
      carboplatin through inhibiting repair of platinum-DNA adducts was conducted in
      poor prognosis, acute leukemia patients. EXPERIMENTAL DESIGN: Patients received
      fludarabine (10 to 15 mg/m(2) x 5 days), carboplatin (area under the curve 10 to
      12 by continuous infusion over 5 days), followed by escalated doses of topotecan
      infused over 72 hours (fludarabine, carboplatin, topotecan regimen). Twenty-eight
      patients had acute myelogenous leukemia (7 untreated secondary acute myelogenous
      leukemia, 11 in first relapse, and 10 in second relapse or refractory), 1 patient
      had refractory/relapsed acute lymphoblastic leukemia, and 2 patients had
      untreated chronic myelogenous leukemia blast crisis. Six patients had failed an
      autologous stem cell transplant. Patients ranged from 19 to 76 (median 54) years.
      Measurement of platinum-DNA adducts were done in serial bone marrow specimens.
      RESULTS: Fifteen of 31 patients achieved bone marrow aplasia. Clinical responses
      included 2 complete response, 4 complete response with persistent
      thrombocytopenia, and 2 partial response. Prolonged myelosuppression was observed
      with median time to blood neutrophils >/=200/microl of 28 (0 to 43) days and time
      to platelets >/=20,000/microl (untransfused) of 40 (24 to 120) days. Grade 3 or
      greater infections occurred in all of the patients, and there were 2 infection
      related deaths. The nonhematologic toxicity profile was acceptable. Five patients
      subsequently received allografts without early transplant-related mortality.
      Maximum tolerated dose of fludarabine, carboplatin, topotecan regimen was
      fludarabine 15 mg/m(2) x 5, carboplatin area under the curve 12, and topotecan
      2.55 mg/m(2) over 72 hours. An increase in bone marrow, platinum-DNA adduct
      formation between the end of carboplatin infusion and 48 hours after the infusion
      correlated with bone marrow response. CONCLUSIONS: Fludarabine, carboplatin,
      topotecan regimen is a promising treatment based on potential pharmacodynamic
      interactions, which merits additional study in poor prognosis, acute leukemia
      patients.

PMID- 15501960
TI  - Effects of alpha1-acid glycoprotein on the clinical pharmacokinetics of 7
      hydroxystaurosporine.
AB  - OBJECTIVE: UCN-01 (7-hydroxystaurosporine) is a small molecule cyclin-dependent
      kinase modulator currently under clinical development as an anticancer agent. In
      vitro studies have demonstrated that UCN-01 is strongly bound to the acute-phase
      reactant alpha (1)-acid glycoprotein (AAG). Here, we examined the role of protein
      binding as a determinant of the pharmacokinetic behavior of UCN-01 in patients.
      EXPERIMENTAL DESIGN: Pharmacokinetic data were obtained from a group of 41
      patients with cancer receiving UCN-01 as a 72-hour i.v. infusion (dose, 3.6 to 53
      mg/m(2)/day). RESULTS: Over the tested dose range, total drug clearance was
      distinctly nonlinear (P = 0.0076) and increased exponentially from 4.33 mL/hour
      (at 3.6 mg/m(2)/day) to 24.1 mL/hour (at 54 mg/m(2)/day). As individual values
      for AAG increased, values for clearance decreased in a linear fashion (R(2) =
      0.264; P = 0.0008), although the relationship was shallow, and the data showed
      considerable scatter. Interestingly, no nonlinearity in the unbound concentration
      (P = 0.083) or fraction at the peak plasma concentration of UCN-01 was apparent
      (P = 0.744). CONCLUSION: The results suggest the following: (1) that extensive
      binding to AAG may explain, in part, the unique pharmacokinetic profile of UCN-01
      described previously with a small volume of distribution and slow systemic
      clearance, and (2) that measurement of total UCN-01 concentrations in plasma is a
      poor surrogate for that of the pharmacologically active fraction unbound drug.

PMID- 15501961
TI  - Phase I clinical trial of oral curcumin: biomarkers of systemic activity and
      compliance.
AB  - Curcumin, a polyphenolic antioxidant derived from a dietary spice, exhibits
      anticancer activity in rodents and in humans. Its efficacy appears to be related
      to induction of glutathione S-transferase enzymes, inhibition of prostaglandin
      E(2) (PGE(2)) production, or suppression of oxidative DNA adduct (M(1)G)
      formation. We designed a dose-escalation study to explore the pharmacology of
      curcumin in humans. Fifteen patients with advanced colorectal cancer refractory
      to standard chemotherapies consumed capsules compatible with curcumin doses
      between 0.45 and 3.6 g daily for up to 4 months. Levels of curcumin and its
      metabolites in plasma, urine, and feces were analyzed by high-pressure liquid
      chromatography and mass spectrometry. Three biomarkers of the potential activity
      of curcumin were translated from preclinical models and measured in patient blood
      leukocytes: glutathione S-transferase activity, levels of M(1)G, and PGE(2)
      production induced ex vivo. Dose-limiting toxicity was not observed. Curcumin and
      its glucuronide and sulfate metabolites were detected in plasma in the 10 nmol/L
      range and in urine. A daily dose of 3.6 g curcumin engendered 62% and 57%
      decreases in inducible PGE(2) production in blood samples taken 1 hour after dose
      on days 1 and 29, respectively, of treatment compared with levels observed
      immediately predose (P < 0.05). A daily oral dose of 3.6 g of curcumin is
      advocated for Phase II evaluation in the prevention or treatment of cancers
      outside the gastrointestinal tract. PGE(2) production in blood and target tissue
      may indicate biological activity. Levels of curcumin and its metabolites in the
      urine can be used to assess general compliance.

PMID- 15501962
TI  - Effects of recombinant erythropoietin in palliative treatment of unselected
      cancer patients.
AB  - PURPOSE: The purpose is to evaluate relationships between objectively assessed
      exercise capacity and subjectively assessed scoring of physical functioning and
      well-being after erythropoietin treatment in cancer patients on palliative care.
      EXPERIMENTAL DESIGN: Unselected cancer patients (n = 108) who experienced
      progressive cachexia were randomized to receive either anti-inflammatory
      treatment alone (indomethacin) or recombinant erythropoietin plus indomethacin to
      prevent the appearance of disease-induced anemia and thereby protect patients'
      exercise capacity. Follow-up investigations of nutritional status, exercise
      capacity, and health-related quality of life assessed by SF-36 and the European
      Organization for Research and Treatment of Cancer QLQ-C30 were compared. RESULTS:
      Effective treatment by erythropoietin on top of basal whole body anti
      inflammatory treatment was confirmed and indicated by time course changes of
      biochemical, physiologic, and nutritional objectives, whereas individual self
      reported scoring of physical functioning and general health did not indicate a
      clear-cut effectiveness, particularly at moderately subnormal hemoglobin levels.
      CONCLUSIONS: Discrepancies between objective and subjective self-reported
      measures may be either fundamental or indicate scoring limitations for evaluation
      of therapeutic results. Present results demonstrate a clinical benefit of
      erythropoietin treatment in cancer patients with subnormal to normal hemoglobin
      levels, whereas the patients' own subjective scoring was insufficient to sense
      such improvements. The discrepancy may be either fundamental or methodological
      but emphasizes the importance to document therapeutic outcome in both subjective
      and objective perspectives in palliative care of cancer patients.

PMID- 15501963
TI  - Phospho-Akt overexpression in non-small cell lung cancer confers significant
      stage-independent survival disadvantage.
AB  - PURPOSE: Akt is a signal transduction protein that plays a central role in
      inhibiting apoptosis in a variety of cell types including human cancer cells. In
      cell lines derived from human non-small cell lung cancers (NSCLCs), Akt has been
      shown to confer chemoresistance by inhibition of apoptosis in response to
      different chemotherapeutic agents including platinum-based agents, which are
      often the first-line therapy for NSCLCs. Only 20% to 30% of patients with NSCLC
      treated with chemotherapy have clinical evidence of response. The purpose of this
      study is to determine whether or not overexpression of activated Akt [i.e.,
      phosphorylated Akt (pAkt)] is correlated with survival. EXPERIMENTAL DESIGN: We
      studied tumors from 61 patients with NSCLC in three tissue microarrays. All
      patients were followed for a period of 10 years or until death. The arrays were
      studied immunohistochemically with antibodies against pAkt, p53, and Ki-67.
      RESULTS: There was a statistically significant difference in survival between the
      14 patients with strong pAkt staining and the 47 patients with weak to absent
      pAkt staining both by log-rank (P = 0.0416) and Breslow analysis (P = 0.0446).
      Difference in survival time with respect to pAkt status was also statistically
      significant even after accounting for stage at diagnosis (P = 0.004). Neither p53
      nor Ki-67 was a statistically significant prognostic factor. CONCLUSIONS:
      Overexpression of pAkt is an independent prognostic factor. Additional studies of
      human NSCLCs are warranted to drive the development of targeted tumor-specific
      antineoplastic therapies.

PMID- 15501964
TI  - Modulation of pulmonary leukotriene B4 production by cyclooxygenase-2 inhibitors
      and lipopolysaccharide.
AB  - PURPOSE: Emerging data continue to link carcinogenesis to inflammatory events
      involving the eicosanoid metabolic pathways. We therefore evaluated the effects
      of cyclooxygenase (COX)-2 inhibition on leukotriene (LT) B(4) synthesis in the
      lungs of active smokers, as part of a pilot lung cancer chemoprevention study
      with celecoxib (Celebrex), an oral COX-2 inhibitor. EXPERIMENTAL DESIGN:
      Bronchoalveolar lavage was performed before celecoxib treatment and after 1 month
      of celecoxib treatment to recover alveolar macrophages (AMs) and lining fluid for
      study. After harvest, AMs were immediately stimulated in vitro with the calcium
      ionophore A23187. AMs obtained from smokers before treatment and from ex-smoker
      control subjects were also cultured overnight with SC58236, a selective COX-2
      inhibitor, with or without lipopolysaccharide stimulation. RESULTS: Treatment
      with oral celecoxib only modestly increased LTB(4) levels in bronchoalveolar
      lavage, without increasing the mRNA transcription of 5-lipoxygenase (5-LOX) or 5
      LOX-activating protein in AMs, whereas the acute calcium ionophore-stimulated
      LTB(4) production from smokers' AMs was markedly increased by 10.6-fold. In
      addition, smokers' AMs were twice as responsive in producing LTB(4) when exposed
      to lipopolysaccharide compared with ex-smokers' AMs. Concomitant COX-2 inhibition
      with SC58236, however, did not significantly impact these changes, whereas the 5
      LOX inhibitor Zileuton blocked the generation of LTB(4) in a dose-responsive
      manner. Finally, cycloheximide increased the production of LTB(4) under all
      conditions, suggesting a shunting phenomenon and/or the presence of pathway
      inhibitors. CONCLUSIONS: Our findings suggest that whereas oral celecoxib is
      capable of modulating LTB(4) production in the lung microenvironment, under
      physiologic conditions, this effect is probably not functionally significant.

PMID- 15501965
TI  - Induction of endothelial nitric oxide synthase expression by melanoma sensitizes
      endothelial cells to tumor necrosis factor-driven cytotoxicity.
AB  - PURPOSE: The cascade of molecular events leading to tumor necrosis factor (TNF)
      mediated tumor regression is still incompletely elucidated. We investigated the
      role of endothelial nitric oxide synthase in determining the tumor-selective
      activity of TNF. EXPERIMENTAL DESIGN: Using quantitative real-time PCR,
      endothelial nitric oxide synthase gene levels were measured in melanoma
      metastases of the skin and normal skin biopsies obtained from 12 patients before
      undergoing TNF-based therapy. In vitro, the ability of melanoma cells supernatant
      to affect endothelial nitric oxide synthase transcription by endothelial cells
      and the influence of nitric oxide synthase inhibition on TNF cytotoxicity toward
      endothelial cells was evaluated. RESULTS: Endothelial nitric oxide synthase
      transcript abundance resulted significantly greater in tumor samples rather than
      in normal skin samples and in patients showing complete response to TNF-based
      treatment rather than in those showing partial/minimal response. In vitro,
      melanoma cells' supernatant induced endothelial nitric oxide synthase gene
      expression by endothelial cells. Nitric oxide synthase inhibition slowed
      endothelial cells proliferation and, if induced before TNF administration,
      decreased the cytokine-mediated cytotoxicity on endothelial cells. CONCLUSIONS:
      Taken together, these findings support the hypothesis that high expression of
      endothelial nitric oxide synthase in the tumor microenvironment might increase or
      be a marker for endothelial cells sensitivity to TNF. These observations may have
      important prognostic and/or therapeutic implications in the clinical setting.

PMID- 15501966
TI  - Proteomic analysis of human acute leukemia cells: insight into their
      classification.
AB  - PURPOSE: French-American-British (FAB) classification of acute leukemia with
      genetic heterogeneity is important for treatment and prognosis. However, the
      distinct protein profiles that contribute to the subtypes and facilitate
      molecular definition of acute leukemia classification are still unclear.
      EXPERIMENTAL DESIGN: The proteins of leukemic cells from 61 cases of acute
      leukemia characterized by FAB classification were separated by two-dimensional
      electrophoresis, and the differentially expressed protein spots were identified
      by both matrix-assisted laser desorption/ionization-time-of-flight-mass
      spectrometry (MALDI-TOF-MS) and tandem electrospray ionization MS (ESI-MS/MS).
      RESULTS: The distinct protein profiles of acute leukemia FAB types or subtypes
      were successfully explored, including acute myeloid leukemia (AML), its subtypes
      (M2, M3, and M5) and acute lymphoid leukemia (ALL), which were homogeneous within
      substantial samples of the respective subgroups but clearly differed from all
      other subgroups. We found a group of proteins that were highly expressed in M2
      and M3, rather than other subtypes. Among them, myeloid-related proteins 8 and 14
      were first reported to mark AML differentiation and to differentiate AML from
      ALL. Heat shock 27 kDa protein 1 and other proteins that are highly expressed in
      ALL may play important roles in clinically distinguishing AML from ALL. Another
      set of proteins up-regulated was restricted to granulocytic lineage leukemia.
      High-level expression of NM23-H1 was found in all but the M3a subtype, with
      favorable prognosis. CONCLUSIONS: These data have implications in delineating the
      pathways of aberrant gene expression underlying the pathogenesis of acute
      leukemia and could facilitate molecular definition of FAB classification. The
      extension of the present analysis to currently less well-defined acute leukemias
      will identify additional subgroups.

PMID- 15501967
TI  - Tumor cells circulate in the peripheral blood of all major carcinomas but not in
      healthy subjects or patients with nonmalignant diseases.
AB  - PURPOSE: The purpose of this study was to determine the accuracy, precision, and
      linearity of the CellSearch system and evaluate the number of circulating tumor
      cells (CTCs) per 7.5 mL of blood in healthy subjects, patients with nonmalignant
      diseases, and patients with a variety of metastatic carcinomas. EXPERIMENTAL
      DESIGN: The CellSearch system was used to enumerate CTCs in 7.5 mL of blood.
      Blood samples spiked with cells from tumor cell lines were used to establish
      analytical accuracy, reproducibility, and linearity. Prevalence of CTCs was
      determined in blood from 199 patients with nonmalignant diseases, 964 patients
      with metastatic carcinomas, and 145 healthy donors. RESULTS: Enumeration of
      spiked tumor cells was linear over the range of 5 to 1,142 cells, with an average
      recovery of >/=85% at each spike level. Only 1 of the 344 (0.3%) healthy and
      nonmalignant disease subjects had >/=2 CTCs per 7.5 mL of blood. In 2,183 blood
      samples from 964 metastatic carcinoma patients, CTCs ranged from 0 to 23,618 CTCs
      per 7.5 mL (mean, 60 +/- 693 CTCs per 7.5 mL), and 36% (781 of 2,183) of the
      specimens had >/=2 CTCs. Detection of >/=2 CTCs occurred at the following rates:
      57% (107 of 188) of prostate cancers, 37% (489 of 1,316) of breast cancers, 37%
      (20 of 53) of ovarian cancers, 30% (99 of 333) of colorectal cancers, 20% (34 of
      168) of lung cancers, and 26% (32 of 125) of other cancers. CONCLUSIONS: The
      CellSearch system can be standardized across multiple laboratories and may be
      used to determine the clinical utility of CTCs. CTCs are extremely rare in
      healthy subjects and patients with nonmalignant diseases but present in various
      metastatic carcinomas with a wide range of frequencies.

PMID- 15501968
TI  - Expression of deltaNp73 predicts poor prognosis in lung cancer.
AB  - PURPOSE: DeltaNp73 is an isoform of the p53 homologue p73, which lacks an NH(2)
      terminal transactivation domain and antagonizes the induction of gene expression
      by p53/p73. The aim of this study was to detect DeltaNp73 expression in lung
      cancer and to evaluate the relationship between the DeltaNp73 expression level
      and the prognosis of patients with resected lung cancer. EXPERIMENTAL DESIGN: We
      used immunohistochemistry to analyze the protein expression of DeltaNp73 in
      paraffin-embedded tumor samples from 132 well-characterized lung cancer patients
      and compared the expression level of DeltaNp73, clinical variables, and survival
      outcome. RESULTS: Positive expression of DeltaNp73 was detected mainly in the
      cytoplasm of tumor cells in 77 of 132 patients (58.3%) with lung cancer. The
      incidence of positive expression of DeltaNp73 was 52.2, 50.0, and 70.2% in
      patients with stage I, II, and III, respectively (P = 0.04). Positive expression
      of DeltaNp73 was associated with gender but not associated with age, histologic
      type, pathological stage, pathological T status, and pathological N status. Lung
      cancer patients with positive DeltaNp73 expression had a poorer prognosis than
      those with negative DeltaNp73 expression. In addition, multivariate analysis of
      the clinicopathological characteristics of lung cancer indicated that positive
      expression of DeltaNp73 was a significant independent factor for predicting poor
      prognosis (P < 0.0001, risk ratio = 3.39). CONCLUSIONS: Expression of DeltaNp73
      may be a useful marker for predicting poor prognosis of patients who underwent
      resection of lung cancer.

PMID- 15501969
TI  - Is a lymph node detected by the dye-guided method a true sentinel node in gastric
      cancer?
AB  - PURPOSE: A sentinel node is defined as the initial lymph node, to which cancer
      cells metastasize from a primary tumor. Recently, sentinel node navigation
      surgery has been done using the dye-guided method. However, no study has shown
      that a lymph node detected by the dye-guided method is the true sentinel node
      from the viewpoint of micrometastasis. Micrometastases of lymph nodes, in which
      no metastasis was found by H&E staining, were examined to establish whether a
      lymph node detected by the dye-guided method is the true sentinel node.
      EXPERIMENTAL DESIGN: Isosulfan blue was injected endoscopically as the dye-guided
      method at a submucosal lesion of early gastric cancer. Total 345 lymph nodes,
      including 150 blue-dyed lymph nodes and 195 nondyed lymph nodes were collected
      from 57 patients and each was quartered. Two quarters were examined
      histologically by H&E staining and cytokeratin staining. The other specimens were
      used for quantitative reverse transcription-PCR of CEA and CK20 mRNAs. RESULTS:
      Lymph node disease was not found in any of 345 lymph nodes from the 57 patients
      by routine H&E staining. By contrast, either CEA or CK20 mRNA expression was
      detected in 21 of 345 lymph nodes obtained from the 10 (18%) of 57 patients by
      quantitative reverse transcription-PCR. Eight of the 21 micrometastasis-positive
      lymph nodes were confirmed to be positive for cytokeratin staining. Although
      micrometastasis of nondyed lymph nodes was found in three cases, these were
      included in the 10 cases with micrometastasis of blue-dyed nodes, such that there
      was no patient who only had micrometastasis in nondyed nodes. Six of 10 cases
      were micrometastasis-positive in a single node; all six were blue-dyed nodes.
      CONCLUSION: A lymph node detected by the dye-guided method should be a true
      sentinel node to which cancer cells metastasize initially.

PMID- 15501970
TI  - Lymphatic vessel density and vascular endothelial growth factor-C expression
      correlate with malignant behavior in human pancreatic endocrine tumors.
AB  - Metastatic dissemination of tumor cells to regional lymph nodes is a common early
      feature of many human cancers including pancreatic adenocarcinoma. In contrast,
      lymph node metastasis is more variably observed in pancreatic endocrine tumors.
      The objective of this study was to assess the lymphatic system of human
      pancreatic endocrine tumors and correlate this to clinical behavior.
      Immunohistochemistry was performed using antibodies to two recently identified
      markers of lymphatic endothelium, namely, LYVE-1 and podoplanin, and to the
      lymphangiogenic factor vascular endothelial growth factor (VEGF)-C. As has been
      reported previously, we observed that in the normal pancreas, islets of
      Langerhans are devoid of intra-islet lymphatics, but that lymphatics are present
      in connective tissue in association with ducts and blood vessels. We found that
      both benign and malignant pancreatic endocrine tumors contain intratumoral
      lymphatic vessels. Lymphatic vessel density was related to the size of the tumor
      in benign tumors and to the presence of liver metastasis but not to lymph node
      metastasis in malignant tumors. VEGF-C was expressed in tumor cells: 4 of 19
      (21%) benign tumors were positive, whereas 6 of 9 (67%) borderline tumors and 9
      of 11 (82%) carcinomas were positive. These findings strongly suggest that
      lymphangiogenesis occurs in pancreatic endocrine tumors and that lymphatic
      invasion and the development of metastases are associated with VEGF-C expression.

PMID- 15501971
TI  - Effect of human papillomavirus-16 infection on CD8+ T-cell recognition of a wild
      type sequence p53264-272 peptide in patients with squamous cell carcinoma of the
      head and neck.
AB  - PURPOSE: Wild-type sequence (wt) p53 peptides are attractive candidates for
      broadly applicable cancer vaccines, currently considered primarily for patients
      whose tumors overexpress p53. Circumstances exist, however, where increased p53
      degradation may result in appreciable presentation of p53-derived peptides,
      despite low p53 expression. Squamous cell carcinoma of the head and neck is
      associated with oncogenic human papillomavirus (HPV) subtypes, which inactivate
      p53 through proteasomal degradation. The criterion of p53 overexpression would
      exclude these individuals from wt p53-based immunotherapy. EXPERIMENTAL DESIGN:
      We tested the correlation of HPV infection with enhanced antigenicity of the p53
      protein and postulated that removal of HPV-16(+) tumors with enhanced p53(264)
      (272) peptide presentation might lead to a drop in T cells specific for this
      peptide in vivo. Circulating frequencies of T cells specific for the HLA
      A*0201:p53(264)-(272) complex were measured ex vivo using dimeric HLA:peptide
      complexes in 15 head and neck cancer patients before and 6 months after tumor
      excision. RESULTS: CD8+ T-cell recognition of HLA A*0201 restricted wt p53(264)
      (272) peptide presented by HPV-16(-) squamous cell carcinoma of the head and neck
      lines was enhanced by HPV-16 E6 expression, sometimes exceeding that of a
      naturally transformed, HPV-16(+) wt p53 expressing squamous cell carcinoma of the
      head and neck cell line. In patients with HPV-16(-) tumors, the frequency of wt
      p53(264-272)-specific T cells remained largely unchanged after tumor removal.
      However, a significant decline in frequency of anti-p53(264-272) T cells was
      observed postoperatively in HPV-16(+) patients (P < 0.005). CONCLUSIONS:
      Recognition of HPV-associated squamous cell carcinoma of the head and neck
      appears associated with levels of wt p53-specific T cells and inversely with p53
      expression. p53 peptides may be useful tumor antigens for squamous cell carcinoma
      of the head and neck immunotherapy in addition to viral gene products.

PMID- 15501972
TI  - Concomitant overexpression of cyclooxygenase-2 in HER-2-positive on Smad4-reduced
      human gastric carcinomas is associated with a poor patient outcome.
AB  - PURPOSE: The expression of cyclooxygenase-2 (COX-2) is known to be involved in
      gastric carcinogenesis and tumor progression, but little is known about the
      mechanisms responsible for the up-regulation of COX-2. We examined the
      involvement of two growth factor-signaling systems, HER-2 and transforming growth
      factor (TGF)-beta, in the induction of COX-2 in human gastric cancer tissue.
      EXPERIMENTAL DESIGN: COX-2 expression was detected by immunohistochemistry in
      surgical specimens obtained from 166 patients with advanced gastric cancer;
      possible correlations between the expression of COX-2 and the expression of HER
      2, TGF-beta1, and Smad4, an intracellular mediator that transmits the TGF-beta
      signal, were then analyzed. RESULTS: COX-2 protein was overexpressed in 91
      (54.8%) tumors; COX-2 overexpression was correlated with a differentiated
      histologic type, deep invasion, and positive lymph node metastasis. COX-2 was
      frequently overexpressed in HER-2-positive tumors (19 of 22, 86.4%) and in Smad4
      reduced tumors (67 of 104, 64.4%) but irrelevant to the TGF-beta1 expression
      status. The expression levels of COX-2 and HER-2 and the reduction in Smad4 were
      all associated with a poor patient outcome. A multivariate analysis demonstrated
      a significantly poor outcome for the concomitant overexpression of COX-2 in
      patients with Smad4-reduced tumors. CONCLUSIONS: These results support the
      possibility that signal transduction via HER-2 and the TGF-beta/Smad system may
      be implicated in COX-2 expression and that the reduction of Smad4 may be, in
      part, of causal significance in the TGF-beta-initiated overexpression of COX-2,
      which is associated with a poor prognosis for patients with gastric cancer.

PMID- 15501973
TI  - The spontaneous CD8+ T-cell response to HLA-A2-restricted NY-ESO-1b peptide in
      hepatocellular carcinoma patients.
AB  - PURPOSE: Hepatocellular carcinoma (HCC) can express various cancer-testis
      antigens including NY-ESO-1, members of the SSX family, members of the MAGE
      family, SCP-1, and CTP11. Immunotherapy directed against these antigens is a
      potential alternative treatment for HCC. To date, it remains unclear whether HCC
      patients have spontaneous immune responses to these tumor antigens. The
      objectives of this study were to measure immune responses to NY-ESO-1, a
      promising cancer vaccine candidate, in HCC patients using the HLA-A2-restricted
      NY-ESO-1b peptide (p157-165) to measure cellular responses and whole protein to
      measure antibody responses. EXPERIMENTAL DESIGN: In HLA-A2(+) patients with NY
      ESO-1(+) HCC, we analyzed T-cell antigen-dependent interferon (IFN)-gamma and/or
      Granzyme B release by enzyme-linked immunospot (ELISPOT) assay and IFN-gamma
      producing intracellular cytokine flow cytometry (CytoSpot). As an assay
      independent of T-cell function, we performed tetramer staining. Antibodies to
      whole NY-ESO-1 were assayed by enzyme-linked immunosorbent assay. RESULTS: The
      frequency of specific CD8(+) T-cell responses to NY-ESO-1b in 28 NY-ESO-1
      mRNA(+)HLA-A2(+) HCC patients was 35.7% (10 of 28). The average magnitude of
      effector CD8(+) T cells was 0.3% (89 +/- 59 per 2.5 x 10(4) CD8(+) cells) and
      1.2% as measured by IFN-gamma release ELISPOT and CytoSpot assays, respectively.
      These in vitro induced NY-ESO-1b-specific CD8(+) T cells can also recognize HepG2
      cells transfected with pcDNA3.1-NY-ESO-1 in both IFN-gamma and Granzyme B ELISPOT
      assays. Frequencies of NY-ESO-1b-specific T cells in several patients were
      confirmed by tetramer staining. Nonfunctional tetramer(+)CD8(+) T cells were also
      present. The CD8(+) T-cell response was apparently increased in patients with
      late-stage HCC. A discordance between antibody and CD8(+) T-cell responses in HCC
      patients was observed. CONCLUSIONS: The elevated frequency of specific CD8(+) T
      cell responses to NY-ESO-1b in NY-ESO-1 mRNA(+)HLA-A2(+) HCC patients suggests
      that NY-ESO-1 is appropriate for use in the immunotherapy of HCC patients.

PMID- 15501974
TI  - The absence of human equilibrative nucleoside transporter 1 is associated with
      reduced survival in patients with gemcitabine-treated pancreas adenocarcinoma.
AB  - PURPOSE: Gemcitabine monotherapy is the standard palliative chemotherapy for
      pancreatic adenocarcinoma. Gemcitabine requires plasma membrane nucleoside
      transporter proteins to efficiently enter cells and exert it cytotoxicity. In
      vitro studies have demonstrated that deficiency of human equilibrative nucleoside
      transporter 1 (hENT1), the most widely abundant and distributed nucleoside
      transporter in human cells, confers resistance to gemcitabine toxicity, but the
      distribution and abundance of nucleoside transporters in normal and malignant
      pancreatic tissue is unknown. EXPERIMENTAL DESIGN: We studied tumor blocks from
      normal pancreas and 21 Alberta patients with gemcitabine-treated pancreatic
      cancer. Immunohistochemistry on the formalin-fixed, paraffin-embedded tissues was
      performed with specific hENT1 and human Concentrative Nucleoside Transporter 3
      monoclonal antibodies and scored by a pathologist blinded to clinical outcomes.
      RESULTS: hENT1 was detected in normal Langerhan cells and lymphocytes but not in
      normal glandular elements. Patients in whom all adenocarcinoma cells had
      detectable hENT1 had significantly longer median survivals from gemcitabine
      initiation than those for whom hENT1 was absent in a proportion (10 to 100%) of
      adenocarcinoma cells (median survival, 13 versus 4 months, P = 0.01).
      Immunohistochemistry for human Concentrative Nucleoside Transporter 3 revealed
      moderate to high-intensity staining in all adenocarcinoma tissue samples.
      CONCLUSIONS: Patients with pancreatic adenocarcinoma with uniformly detectable
      hENT1 immunostaining have a significantly longer survival after gemcitabine
      chemotherapy than tumors without detectable hENT1. Immunohistochemistry for hENT1
      shows promise as a molecular predictive assay to appropriately select patients
      for palliative gemcitabine chemotherapy but requires formal validation in
      prospective, randomized trials.

PMID- 15501975
TI  - HDAC6 expression is correlated with better survival in breast cancer.
AB  - PURPOSE: The structure and function of chromatin can be altered by modifications
      to histone. Histone acetylation in vivo is a dynamic reversible process governed
      by histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDAC6 is a
      unique isoform among the HDACs, and a gene expression pattern study, with cDNA
      microarray in MCF-7 cells, showed the HDAC6 gene to be late responsive, estrogen
      induced, and up-regulated. This led us to hypothesize that there was a link
      between levels of HDAC6 expression and the metastatic potential of breast cancer
      and also, therefore, the prognosis of these patients. EXPERIMENTAL DESIGN: In the
      present study, the level of HDAC6 mRNA expression was analyzed with quantitative
      real-time reverse transcription-PCR, in 135 female patients with invasive breast
      cancer. HDAC6 protein expression was also determined by immunohistochemistry. An
      association was sought between HDAC6 expression and various clinicopathologic
      factors. RESULTS: HDAC6 mRNA was expressed at significantly higher levels in
      breast cancer patients with small tumors measuring less than 2 cm, with low
      histologic grade, and in estrogen receptor alpha- and progesterone receptor
      positive tumors. By contrast, no relationship was found between HDAC6 mRNA
      expression and any of the other clinicopathologic factors, namely, age,
      menopausal status, and axillary lymph node involvement. Patients expressing high
      levels of HDAC6 mRNA and protein had a better prognosis than those expressing low
      levels, in terms of disease-free survival. However, multivariate analysis failed
      to show that HDAC6 mRNA and protein are an independent prognostic factors for
      disease-free survival and overall survival. Furthermore, the patients with high
      levels of HDAC6 mRNA tended to be more responsive to endocrine treatment than
      those with low levels. Specific HDAC6 staining was found in the nucleus of some
      normal epithelial cells and in the cytoplasm of the majority of cancer cells.
      Although postmenopausal patients showed higher HDAC6 protein expression, there
      were no relationship between protein expression and any other clinicopathologic
      factors. CONCLUSIONS: We conclude that the levels of HDAC6 mRNA expression may
      have potential both as a marker of endocrine responsiveness and also as a
      prognostic indicator in breast cancer. Additional investigations are warranted
      concerning the relationship between HDAC6 expression and response to endocrine
      therapy.

PMID- 15501976
TI  - Rat sodium iodide symporter for radioiodide therapy of cancer.
AB  - Design and development of new approaches for targeted radiotherapy of cancer and
      improvement of therapeutic index by more local radiation therapy are very
      important issues. Adenovirus-mediated delivery of the sodium iodide symporter
      (NIS) gene to cancer cells is a powerful technique to concentrate lethal
      radiation in tumor cells and eradicate tumors with increased therapeutic index. A
      replication-defective adenoviral vector expressing the rat NIS gene (Ad-rNIS) was
      used for in vitro gene delivery and into human prostate cancer xenografts to
      study antitumor effect. Robust function of the rat symporter was detected in
      DU145, T47D, and HCT-15 human cancer cell lines transduced with Ad-rNIS. All
      three cancer cell lines successfully transferred functionally active rat
      symporter to the plasma membrane, resulting in very high levels of iodine-125
      accumulation. Three-dimensional multicellular tumor spheroids derived from DU145
      human prostate cancer cells were transduced with Ad-rNIS and incubated with
      (131)I for 24 hours. After treatment, spheroids rapidly decreased in size and
      disappeared within 10 days. In vivo data revealed an inhibition of tumor growth
      in athymic nude mice after intratumoral Ad-rNIS injection followed by (131)I
      administration. Eighty-eight percent of experimental mice survived >30 days,
      whereas control groups had only 18% survival >30 days. This is the first report
      that demonstrates the rat NIS gene can effectively induce growth arrest of human
      tumor xenografts after in vivo adenoviral gene delivery and (131)I
      administration. The data confirm our hypothesis that the rat NIS gene is an
      attractive suicide gene candidate for cancer treatment.

PMID- 15501977
TI  - Monitoring the response of orthotopic bladder tumors to granulocyte macrophage
      colony-stimulating factor therapy using the prostate-specific antigen gene as a
      reporter.
AB  - PURPOSE: Although orthotopic animal models of cancer best reflect the disease in
      humans, a major drawback of these models is the inability to monitor tumor growth
      accurately. Our aims were to produce a bladder tumor cell line (MB49) that
      secreted human prostate-specific antigen (PSA), analyze the feasibility and
      accuracy of PSA as a biomarker for monitoring orthotopic bladder tumor growth,
      and evaluate the effectiveness of granulocyte macrophage colony-stimulating
      factor (GM-CSF) gene therapy using this model. EXPERIMENTAL DESIGN: PSA secretion
      was assessed after both s.c. and orthotopic implantation of MB49-PSA cells in
      C57BL/6 mice. PSA levels in mouse serum and urine samples were monitored at 2- to
      3-day intervals by ELISA. Using the orthotopic model, mice with confirmed tumors
      were given liposome-mediated GM-CSF gene therapy twice a week for 3 weeks
      intravesically and PSA levels monitored. RESULTS: The MB49-PSA cells behaved
      similarly as the parental cell line and produced high levels of PSA both in vitro
      and in vivo. In the s.c. model, the level of PSA produced correlated with tumor
      volume (r = 0.96). In the orthotopic model, PSA could be detected in serum and
      urine on the fourth day after implantation. PSA levels over the treatment period
      indicated that tumor growth was inhibited by GM-CSF gene therapy. Up to 50% of
      the treated mice were cured. Cytokine array analysis revealed that GM-CSF gene
      therapy induced the production of other cytokines and chemokines. CONCLUSIONS:
      MB49 cells modified to secrete PSA are a reliable method to evaluate therapeutic
      modalities for bladder cancer.

PMID- 15501978
TI  - Treatment of neuroblastoma meningeal carcinomatosis with intrathecal application
      of alpha-emitting atomic nanogenerators targeting disialo-ganglioside GD2.
AB  - Labeling of specific antibodies with bifunctional chelated Actinium-225 ((225)Ac;
      an alpha generator) allows the formation of new, highly potent and selective
      alpha-emitting anticancer drugs. We synthesized and evaluated a
      radioimmunoconjugate based on 3F8, an IgG(3) antibody that specifically binds to
      ganglioside GD2, which is overexpressed by many neuroectodermal tumors including
      neuroblastoma. The (225)Ac-1,4,7,10-tetra-azacylododecane (DOTA)-3F8 construct
      was evaluated for radiochemical purity and sterility, immunoreactivity,
      cytotoxicity in vitro, induction of apoptosis on GD2-positive cells, as well as
      for pharmacological biodistribution and metabolism of the (225)Ac generator and
      its daughters in a nude mouse xenograft model of neuroblastoma. The (225)Ac-3F8
      showed an IC(50) of 3 Bq/ml (80 pCi/ml) on the neuroblastoma cell line, NMB7, in
      vitro. Apoptosis of these cells was not observed. Biodistribution in mice showed
      specific targeting of a subcutaneous tumor; there was redistribution of the
      (225)Ac daughter nuclides mainly from blood to kidneys and to small intestine.
      Toxicity was examined in cynomolgus monkeys. Monkeys injected with 1 to 3 doses
      of intrathecal (225)Ac-3F8 radioimmunoconjugate (80 to 150 kBq/kg total dose) did
      not show signs of toxicity based on blood chemistry, complete blood counts, or by
      clinical evaluations. Therapeutic efficacy of intrathecal (225)Ac-3F8 was studied
      in a nude rat xenograft model of meningeal carcinomatosis. The (225)Ac-3F8
      treatment improved survival 2-fold from 16 to 34 days (P = 0.01). In conclusion,
      in vivo alpha generators targeted by 3F8 warrant additional study as a possible
      new approach to the treatment of carcinomatous meningitis.

PMID- 15501979
TI  - Effect of rapamycin alone and in combination with antiangiogenesis therapy in an
      orthotopic model of human pancreatic cancer.
AB  - PURPOSE: The overall 5-year survival of patients with pancreatic cancer remains
      <5%. Novel therapeutic strategies are needed. We examined the effect of
      rapamycin, alone and in combination with antiangiogenesis therapy, on pancreatic
      cancer in vivo. EXPERIMENTAL DESIGN: Human pancreatic cancer AsPC-1 cells were
      orthotopically injected into severe combined immunodeficient/beige mice to
      evaluate primary tumor growth and liver metastasis after treatment with rapamycin
      alone or in combination with anti-vascular endothelial growth factor antibody
      2C3. Tumor cell proliferation was determined by bromodeoxyuridine incorporation.
      To detect tumor cell apoptosis, the terminal deoxynucleotidyl transferase
      mediated dUTP nick end labeling assay was used. Tumor angiogenesis was
      investigated by using a monoclonal anti-CD31 antibody. All statistical tests were
      two-sided. RESULTS: Rapamycin, alone and in combination with 2C3, strongly
      inhibited primary and metastatic tumor growth in an orthotopic pancreatic cancer
      animal model. Furthermore, the combination therapy significantly improved the
      effect on liver metastasis compared with single treatment with either rapamycin
      (P = 0.0128) or 2C3 (P = 0.0099). Rapamycin alone inhibited pancreatic tumor cell
      proliferation, induced apoptosis, and decreased tumor angiogenesis. Nevertheless,
      the combination therapy showed a significant, stronger inhibition of tumor cell
      proliferation (P = 0.0002 versus rapamycin alone and P < 0.0001 versus 2C3
      alone). The induction of apoptosis was significantly higher than in the rapamycin
      treated group (P = 0.0039). Additionally, the combination therapy further
      improved suppression of tumor cell angiogenesis compared with rapamycin treatment
      (P = 0.029) CONCLUSIONS: Our studies propose new therapeutic strategies to
      inhibit both primary and metastatic tumor growth in pancreatic cancer.
      Considering the fact that liver metastasis is a crucial problem in advanced
      stages of pancreatic cancer, the combination therapy of rapamycin plus anti
      vascular endothelial growth factor antibody 2C3 is a significant advantage
      compared with single treatment with rapamycin.

PMID- 15501980
TI  - Fibrinogen-coated droplets of olive oil for delivery of docetaxel to a
      fibrin(ogen)-rich ascites form of a murine mammary tumor.
AB  - Micronized droplets of olive oil loaded with docetaxel and coated with functional
      fibrinogen were administered intraperitoneally to mice bearing the fibrin(ogen)
      rich ascites form of the TA3/St mammary tumor. When compared with docetaxel
      administered intraperitoneally as its commercial formulation (i.e., Taxotere),
      docetaxel-loaded oil droplets coated with murine fibrinogen prolonged the median
      survival time of tumor-bearing mice from 14.5 to 29.5 days. Drug-free oil
      droplets provided no therapeutic benefit. Significantly more docetaxel was
      associated with tumor cells 24 and 48 hours after administration of the drug in
      fibrinogen-coated oil droplets than after its administration as Taxotere.
      Consistent with a role for thrombin in the retention of fibrinogen-coated oil
      droplets within the tumor microenvironment, hirudin significantly reduced the
      association of tumor cells with docetaxel delivered in fibrinogen-coated oil
      droplets and, at the same time, reduced the therapeutic efficacy of the droplets
      to that of Taxotere. Importantly, fibrinogen-coated oil droplets formed rosettes
      with tumor cells in vivo, a process prevented by hirudin. Although mice treated
      with oil droplets developed antifibrinogen antibodies, those antibodies seemed to
      be inconsequential. Taken together, our results and observations indicate
      fibrinogen-coated oil droplets markedly improve the therapeutic efficacy of
      docetaxel for the treatment of a mammary tumor grown in ascites form, a
      consequence of thrombin-mediated retention of the drug-loaded droplets within the
      tumor microenvironment.

PMID- 15501981
TI  - The in vitro and in vivo effects of re-expressing methylated von Hippel-Lindau
      tumor suppressor gene in clear cell renal carcinoma with 5-aza-2'-deoxycytidine.
AB  - PURPOSE: Clear cell renal carcinoma (ccRCC) is strongly associated with loss of
      the von Hippel-Lindau (VHL) tumor suppressor gene. The VHL gene is functionally
      lost through hypermethylation in up to 19% of sporadic ccRCC cases. We theorized
      that re-expressing VHL silenced by methylation in ccRCC cells, using a hypo
      methylating agent, may be an approach to treatment in patients with this type of
      cancer. We test the ability of two hypo-methylating agents to re-express VHL in
      cell culture and in mice bearing human ccRCC and evaluate the effects of re
      expressed VHL in these models. EXPERIMENTAL DESIGN: Real-time reverse
      transcription-PCR was used to evaluate the ability of zebularine and 5-aza-2'
      deoxycytidine (5-aza-dCyd) to re-express VHL in four ccRCC cell lines with
      documented VHL gene silencing through hypermethylation. We evaluated if the VHL
      re-expressed after hypo-methylating agent treatment could recreate similar
      phenotypic changes in ccRCC cells observed when the VHL gene is re-expressed via
      transfection in cell culture and in a xenograft mouse model. Finally we evaluate
      global gene expression changes occurring in our cells, using microarray analysis.
      RESULTS: 5-Aza-dCyd was able to re-express VHL in our cell lines both in culture
      and in xenografted murine tumors. Well described phenotypic changes of VHL
      expression including decreased invasiveness into Matrigel, and decreased vascular
      endothelial growth factor and glucose transporter-1 expression were observed in
      the treated lines. VHL methylated ccRCC xenografted tumors were significantly
      reduced in size in mice treated with 5-aza-dCyd. Mice bearing nonmethylated but
      VHL-mutated tumors showed no tumor shrinkage with 5-aza-dCyd treatment.
      CONCLUSION: Hypo-methylating agents may be useful in the treatment of patients
      having ccRCC tumors consisting of cells with methylated VHL.

PMID- 15501982
TI  - Troglitazone acts on cellular pH and DNA synthesis through a peroxisome
      proliferator-activated receptor gamma-independent mechanism in breast cancer
      derived cell lines.
AB  - PURPOSE: The purpose of this study was to assess whether troglitazone (TRO) would
      induce cellular acidosis by inhibiting Na(+)/H(+) exchanger (NHE) 1 in breast
      carcinoma-derived cell lines and, if so, whether cellular acidosis would be
      associated with a reduction in proliferation. EXPERIMENTAL DESIGN: Intracellular
      pH (pH(i)) and acid extrusion capacity after an exogenous acid load were assayed
      using (2, 7)-biscarboxyethyl-5(6)-carboxyfluorescein in MCF-7 and MDA-MB-231
      cells treated with TRO. Radiolabeled thymidine incorporation was used to assess
      DNA synthesis. Peroxisome proliferator-activated receptor (PPAR) gamma
      involvement was assessed using an antagonist and PPARgamma(-/-) NIH3T3 cells.
      RESULTS: TRO induced a prompt (<4 minute) and severe cellular acidosis in both
      MCF-7 (7.54 +/- 0.23 to 6.77 +/- 0.06; P < 0.001) and MDA-MB-231 cells (7.38 +/-
      0.18 to 6.89 +/- 0.25; P < 0.05) after 12 minutes, without increasing acid
      production. Acid extrusion as assessed by the response to an exogenous acid load
      (NH(4)Cl pulse) was markedly blunted (MDA-MB-231, P < 0.01) or eliminated (MCF-7,
      P < 0.001). Chronic exposure to TRO resulted in NHE1 activity reduction (P <
      0.05) and a dose-dependent decrease in DNA synthesis (<75% inhibition at 100
      micromol/L; P < 0.001 and P < 0.01 for MCF-7 and MDA-MB-231, respectively)
      associated with a decreased number of viable cells. TRO-mediated inhibition of
      proliferation was not reversed by the presence of the PPARgamma inhibitor GW9662
      and was demonstrable in PPARgamma(-/-) NIH3T3 cells, consistent with a PPARgamma
      independent mechanism. CONCLUSIONS: TRO induces marked cellular acidosis in MCF-7
      and MDA-MD-231 cells. Sustained acidosis is consonant with decreased
      proliferation and growth that is not reversed by a PPARgamma antagonist. Our
      results support a NHE-mediated action of TRO that exerts its effect independent
      of PPARgamma.

PMID- 15501983
TI  - Targeting mammalian target of rapamycin synergistically enhances chemotherapy
      induced cytotoxicity in breast cancer cells.
AB  - PURPOSE: The serine-threonine kinase mammalian target of rapamycin has emerged as
      a potential target for cancer therapy. Rapamycin and rapamycin analogs are
      undergoing clinical trials and have induced clinical responses in a subgroup of
      patients. Rapamycin has also been reported to enhance the efficacy of several
      cytotoxic agents. The aim of this study was to determine the nature of the
      interactions between rapamycin and chemotherapeutic agents used as first- and
      second-line agents against breast cancer. EXPERIMENTAL DESIGN: We performed a
      multiple drug effect/combination index isobologram analysis in cells sensitive
      and resistant to rapamycin alone in vitro, and we evaluated the in vivo efficacy
      of combination therapy in a rapamycin-sensitive model. RESULTS: In vitro,
      synergistic interactions were observed in combinations with paclitaxel,
      carboplatin, and vinorelbine. Additive effects were observed in combinations with
      doxorubicin and gemcitabine. Rapamycin dramatically enhanced paclitaxel- and
      carboplatin-induced apoptosis. This effect was sequence dependent and mediated at
      least partly through caspase activation. Furthermore, rapamycin enhanced
      chemosensitivity to paclitaxel and carboplatin in HER2/neu-overexpressing cells,
      suggesting a potential approach to these poorly behaving tumors. Cell lines that
      are resistant to the growth-inhibitory effect of rapamycin were also resistant to
      rapamycin-mediated chemosensitization. In vivo, rapamycin combined with
      paclitaxel resulted in a significant reduction in tumor volume compared with
      either agent alone in rapamycin-sensitive tumors. CONCLUSIONS: Rapamycin
      potentiates the cytotoxicity of selected chemotherapeutic agents in cell lines
      sensitive to the effects of rapamycin due to aberrations in the
      phosphatidylinositol 3'-kinase/Akt pathway, suggesting that combination therapy
      may be effective in patients selected for aberrations in this pathway.

PMID- 15501984
TI  - Heteroclitic CD33 peptide with enhanced anti-acute myeloid leukemic
      immunogenicity.
AB  - The goal of these studies was to engineer a synthetic CD33 peptide with enhanced
      immunogenicity for the induction of acute myeloid leukemia (AML)-specific CTLs.
      Eight modified CD33 peptides YLISGDSPV, YIGSGDSPV, YIIIGDSPV, YIILGDSPV,
      YIISGISPV, YIISGDLPV, YIISGDSWV and YIISGDSPL were designed for increased HLA
      A2.1 or T cell receptor affinity and compared with the native CD33(65-73)
      peptide, AIISGDSPV, for enhanced immunogenicity. The YLISGDSPV peptide was found
      to be the most immunogenic epitope producing highly cytolytic CTLs against AML
      target cells. The CTLs generated withYLISGDSPV peptide showed CD33 peptide
      specificity through targeting of both native (AIISGDSPV) and modified (YLISGDSPV)
      peptide presenting EBV-BLCL. The CTL cultures displayed a distinct phenotype
      consisting of a high percentage of activated memory (CD69(+)/CD45RO(+))-CD8(+)and
      a low percentage of naive (CD45RA(+)/CCR7(+))-CD8(+)cells. In addition, T-cell
      clones specific to the YLISGDSPV peptide were isolated and characterized to
      target AML cells. The clones exhibited both HLA-A2.1-restricted and AML cell
      specific cytotoxicity that was mediated through a granule-dependent pathway. More
      importantly, the CTL clones did not lyse or inhibit the proliferation of normal
      CD34(+) progenitor cells. In conclusion, we report on the identification of a
      highly immunogenic heteroclitic YLISGDSPV CD33 epitope that is a promising
      candidate for immunotherapy targeting AML.

PMID- 15501985
TI  - Recognition of adult T-cell leukemia/lymphoma cells by CD4+ helper T lymphocytes
      specific for human T-cell leukemia virus type I envelope protein.
AB  - PURPOSE: Human T-cell leukemia virus type I (HTLV-I) can cause an adult T-cell
      leukemia/lymphoma (ATLL). Because ATLL is a life-threatening lymphoproliferative
      disorder and is resistant to chemotherapy, the establishment and enhancement of T
      cell immunity to HTLV-I through the development of therapeutic vaccines could be
      of value. Thus, the identification of HTLV-I epitopes for both CD8(+) and CD4(+)
      T cells should facilitate the development of effective vaccines. Although
      numerous HTLV-I epitopes for CTLs have been identified, few epitopes recognized
      by CD4(+) helper T cells against this virus have been described. EXPERIMENTAL
      DESIGN: Synthetic peptides prepared from several regions of the HTLV-I envelope
      (Env) sequence that were predicted to serve as helper T-cell epitopes were
      prepared with use of computer-based algorithms and tested for their capacity to
      trigger in vitro helper T-cell responses using lymphocytes from normal
      volunteers. RESULTS: The results show that the HTLV-I-Env(317-331), and HTLV-I
      Env(384-398)-reactive helper T lymphocytes restricted by HLA-DQw6 and HLA-DR15,
      respectively, could recognize intact HTLV-I+ T-cell lymphoma cells and, as a
      consequence, secrete lymphokines. In addition, HTLV-I Env(196-210)-reactive
      helper T lymphocytes restricted by HLA-DR9 were able to directly kill HTLV-I+
      lymphoma cells and recognize naturally processed antigen derived from killed HTLV
      I+ lymphoma cells, which was presented to the helper T cells by autologous
      antigen-presenting cells. CONCLUSIONS: The present findings hold relevance for
      the design and optimization of T-cell epitope-based immunotherapy against HTLV-I
      induced diseases such as ATLL.

PMID- 15501986
TI  - Effects of drug loading on the antitumor activity of a monoclonal antibody drug
      conjugate.
AB  - PURPOSE: An antibody-drug conjugate consisting of monomethyl auristatin E (MMAE)
      conjugated to the anti-CD30 monoclonal antibody (mAb) cAC10, with eight drug
      moieties per mAb, was previously shown to have potent cytotoxic activity against
      CD30(+) malignant cells. To determine the effect of drug loading on antibody-drug
      conjugate therapeutic potential, we assessed cAC10 antibody-drug conjugates
      containing different drug-mAb ratios in vitro and in vivo. EXPERIMENTAL DESIGN:
      Coupling MMAE to the cysteines that comprise the interchain disulfides of cAC10
      created an antibody-drug conjugate population, which was purified using
      hydrophobic interaction chromatography to yield antibody-drug conjugates with
      two, four, and eight drugs per antibody (E2, E4, and E8, respectively). Antibody
      drug conjugate potency was tested in vitro against CD30(+) lines followed by in
      vivo xenograft models. The maximum-tolerated dose and pharmacokinetic profiles of
      the antibody-drug conjugates were investigated in mice. RESULTS: Although
      antibody-drug conjugate potency in vitro was directly dependent on drug loading
      (IC(50) values E8<E4<E2), the in vivo antitumor activity of E4 was comparable
      with E8 at equal mAb doses, although the E4 contained half the amount of MMAE per
      mAb. E2 was also an active antitumor agent but required higher doses. The maximum
      tolerated dose of E2 in mice was at least double that of E4, which in turn was
      twice that of E8. MMAE loading affected plasma clearance, as E8 cleared 3-fold
      faster than E4 and 5-fold faster than E2. CONCLUSIONS: By decreasing drug loading
      per antibody, the therapeutic index was increased demonstrating that drug loading
      is a key design parameter for antibody-drug conjugates.

PMID- 15501987
TI  - HMMC-1: a humanized monoclonal antibody with therapeutic potential against
      Mullerian duct-related carcinomas.
AB  - PURPOSE: The purpose of this research was to generate a human monoclonal antibody
      specific to gynecological cancers and to evaluate such an antibody as therapy for
      gynecological cancers. EXPERIMENTAL DESIGN: Transchromosomal KM mice were
      immunized with the human uterine endometrial cancer cell line SNG-S. Hybridomas
      were constructed between spleen cells from KM mice and mouse myeloma cells.
      Reactivity of the antibody was evaluated by immunohistochemistry of pathological
      specimens of gynecological cancers. Cytotoxicity of HMMC-1 against SNG-S cells
      was tested by in vitro cytotoxicity assays. The epitope of HMMC-1 was determined
      by transfection with a panel of glycosyltransferase cDNAs and by inhibition
      assays with chemically synthesized oligosaccharides. RESULTS: HMMC-1 is a human
      IgM monoclonal antibody that reacts positively with mullerian duct-related
      carcinomas with positive rates of 54.6% against uterine endometrial
      adenocarcinoma, 76.9% against uterine cervical adenocarcinoma, and 75.0% against
      epithelial ovarian cancer. HMMC-1 does not react with normal endometrium at
      proliferative or secretory phases, normal uterine cervix, or normal and malignant
      tissue from other organs, whereas it reacts weakly with the epithelium of the
      gall bladder and the collecting duct of the kidney. HMMC-1 exhibits antigen
      dependent and complement-mediated cytotoxicity. Upon cotransfection with cDNAs
      encoding two glycosyltransferases required for fucosylated extended core 1 O
      glycan, mammalian cells express HMMC-1 antigen. Finally, binding of HMMC-1 to SNG
      S cells is inhibited by synthetic Fucalpha1-->2Galbeta1-->4GlcNAcbeta1-
      >3Galbeta1-->3GalNAcalpha1-octyl. CONCLUSIONS: These results indicate that HMMC-1
      specifically recognizes a novel O-glycan structure. The unique specificity and
      cytotoxicity of HMMC-1 strongly suggest a therapeutic potential of this antibody.

PMID- 15501988
TI  - Abrogation of head and neck squamous cell carcinoma growth by epidermal growth
      factor receptor ligand fused to pseudomonas exotoxin transforming growth factor
      alpha-PE38.
AB  - PURPOSE: This study was undertaken to determine whether low intratumoral doses of
      the epidermal growth factor receptor ligand-transforming growth factor alpha (TGF
      alpha) fused to Pseudomonas exotoxin (TGF-alpha-PE38)-abrogated head and neck
      squamous cell carcinoma (HNSCC) tumor growth in vitro and in vivo. EXPERIMENTAL
      DESIGN: In vitro cytotoxicity assays were carried out to determine the
      sensitivity of HNSCC cells to TGF-alpha-PE38. TGF-alpha-PE38-treated HNSCC cells
      were examined by immunoblotting for cleaved poly(ADP-ribose) polymerase to
      evaluate apoptosis. Nude mice bearing established HNSCC xenografts were treated
      with several doses of TGF-alpha-PE38 to evaluate the antitumor efficacy in vivo.
      Tumor sections were stained with terminal deoxynucleotidyl transferase-mediated
      nick end labeling for apoptosis. To determine the effect of oral administration
      of TGF-alpha-PE38, gavage injections of TGF-alpha-PE38 were administered, and the
      esophagus and surrounding soft tissue were then stained for apoptotic cells.
      RESULTS: HNSCC cell lines examined were sensitive to low doses of TGF-alpha-PE38
      (EC(50) in the range of 1.6 to 10 ng/mL). HNSCC cells treated with TGF-alpha-PE38
      undergo apoptosis. Antitumor effects were observed using 0.1 and 0.03 microg of
      TGF-alpha-PE38 administered intratumorally. At these doses, the treatment was
      well tolerated. Tumors treated with the toxin had a higher number of apoptotic
      cells compared with the control tumors. No apoptotic cells were observed in the
      pharyngoesophageal tissues of the mice after gavage administration of the toxin
      suggesting that the toxin could be orally administered without toxicity.
      CONCLUSIONS: These results indicate that topical or intratumoral administration
      of low doses of TGF-alpha-PE38 may demonstrate antitumor effects in HNSCC without
      associated systemic toxicity.

PMID- 15501989
TI  - Bioactive suture: a novel immunotherapy for head and neck cancer.
AB  - PURPOSE: We have proposed to characterize the mechanism through which bioactive
      surgical sutures generate a T(H)1 immune response and to define the immune
      stimulating half-life of the sutures. EXPERIMENTAL DESIGN: Bioactive sutures of
      interferon gamma (IFNgamma), interleukin 2 (IL-2), anti-CD3/CD28, anti-CD3/CD28 +
      IL-2, or anti-CD3/CD28 + IFNgamma sutures were used to stimulate lymphocytes from
      normal donors and from head and neck cancer patients in vitro over a 24-day
      period. Cell supernatants were analyzed by ELISA, and T cells were phenotyped to
      characterize the immune response generated. Intracellular cytokine staining was
      performed to measure the expansion of flu-specific T cells. Electromobility shift
      assay and supershift assay were used to measure the intranuclear DNA binding
      activity of nuclear factor kappaB and its p65 subunit in T cells activated by
      sutures in the presence and absence of a proteasome inhibitor, MG-132. RESULTS:
      Anti-CD3/CD28, anti-CD3/CD28 + IL-2, or anti-CD3/CD28 + IFNgamma generated a
      prolonged T(H)1 immune response for 18 days in vitro. Anti-CD3/CD28 expanded flu
      specific T cells. Activated T cells demonstrated enhanced CD40 ligand (CD40L)
      expression within 72 hours of stimulation, which stimulated other cells to
      secrete IL-12. Stimulated T cells demonstrated increased intranuclear expression
      of nuclear factor-kappaB, which was blocked by MG-132, and also reduced CD40L and
      IL-12 expression. CONCLUSIONS: This is the first report to demonstrate that
      bioactive surgical sutures can generate a prolonged T(H)1 immune response and
      expand flu-specific T cells. Bioactive sutures, which are primarily a T-cell
      stimulant, also stimulated other cells to secrete IL-12 and prolonged the immune
      response. Sutures may provide a novel in situ stimulating strategy for enhancing
      the immune system of cancer patients.

PMID- 15501990
TI  - Aberrant methylation of DPYD promoter, DPYD expression, and cellular sensitivity
      to 5-fluorouracil in cancer cells.
AB  - PURPOSE: Dihydropyrimidine dehydrogenase (DPD), the initial rate-limiting enzyme
      in the degradation of 5-fluorouracil (5-FU), is known to be a principal factor in
      clinical responses to the anticancer agent 5-FU, and various reports have clearly
      demonstrated that DPD activity is closely correlated to mRNA levels. However, the
      regulatory mechanisms of DPD gene (DPYD) expression remain unclear. In this
      study, the regulatory mechanisms have been intensively studied. EXPERIMENTAL
      DESIGN AND RESULTS: A subcloned 3.0-kb fragment of the 5' region of DPYD contains
      a total of 60 CpG sites, suggesting that methylation status may affect the
      repression of DPYD. The clone showed various promoter activities that were
      largely correlated with mRNA levels in most cell lines, except HSC3 and HepG2.
      Bisulfite sequencing analysis revealed that various CpG sites around the
      transcription start site were abnormally methylated in cells with low DPYD
      expression: Reversal of hypermethylation by 5-azacytidine treatment significantly
      increased DPYD expression in HSC3 and HepG2 cells that showed strong promoter
      activity. In HepG2, in vitro methylation of the DPYD promoter directly decreased
      promoter activity, and 5-azacytidine treatment restored higher DPYD expression in
      a dose- and time-dependent manner, along with decreased sensitivity to 5-FU.
      CONCLUSIONS: We found that DPD activity was controlled, at least in part, at the
      transcription level of DPYD and that aberrant methylation of the DPYD promoter
      region acted as one of the repressors of DPYD expression and affected sensitivity
      to 5-FU in cancer cells. Our new results could lead to a more precise
      understanding of the molecular basis of 5-FU response.

PMID- 15501991
TI  - Differential effects on current kinetics by point mutations in the lurcher motif
      of NR1/NR2A receptors.
AB  - The extracellular proton site has emerged as the key site in regulating N-methyl
      d-aspartate (NMDA) receptor function. However, the molecular determinants for the
      proton-sensitive gating of NMDA receptors are still not clearly delineated. The
      highly conserved lurcher motif plays an important role in determining the proton
      sensitivity of NMDA receptors. Mutations of several residues in the lurcher motif
      of either NR1 or NR2A significantly reduce proton sensitivity of recombinant
      NR1/NR2A receptors. It remains uncertain how these residues play a role in proton
      inhibition of NMDA receptors. Mutations of these residues could directly reduce
      the proton affinity. Alternatively, they could alter the proton IC(50) indirectly
      by increasing channel open probability. In the present study, we recorded the
      macroscopic NMDA currents in HEK 293 cells with a piezo-based rapid solution
      exchange system. We show that zinc slows the deactivation of NR1a(A653T)/NR2A
      receptors and NR1a/NR2A(A651T) receptors. However, NR1a(T648C)/NR2A,
      NR1a/NR2A(T646C), NR1a(A649C)/NR2A, NR1a/NR2A(A647C), and NR1a(A653T)/NR2A
      exhibit significantly slower rise time and deactivation time constants under
      nominally zinc-free conditions. Our data suggest that the channel open
      probability for these mutant receptors may be significantly increased. The
      reduction in proton sensitivity by these mutations could be accounted for, at
      least partially, by the increased channel open probability. In contrast,
      NR1a/NR2A(A651T) exhibits normal macroscopic currents, suggesting that the
      reduction of proton sensitivity by this mutation cannot be attributed to any
      significant change of open probability. Further experiments are needed to
      determine the exact role of this residue in proton-sensitive gating of NMDA
      receptors.

PMID- 15501992
TI  - Effect of neocuproine, a copper(i) chelator, on rat bladder function.
AB  - The effects of a specific copper(I)-chelator, neocuproine (NC), and a selective
      copper(II)-chelator, cuprizone, on nonadrenergic-noncholinergic transmitter
      mechanisms in the rat urinary bladder were studied by measuring nerve-evoked
      contractions of bladder strips and voiding function under urethane anesthesia.
      After blocking cholinergic and adrenergic transmission with atropine and
      guanethidine, electrical field stimulation induced bimodal contractions of
      bladder strips. An initial, transient contraction that was blocked by the
      purinergic antagonist, suramin, was significantly enhanced by NC (20 and 200
      microM applied sequentially) but not affected by cuprizone. The facilitating
      effect, which was blocked by suramin and reversible after washout of the drug,
      did not occur following administration of neocuproine-copper(I) complex (NC-Cu).
      NC (20 microM) significantly increased the second, more sustained contraction,
      whereas 200 microM decreased this response. These effects of NC on the sustained
      contractions were not elicited by NC-Cu and not blocked by suramin. The nitric
      oxide synthase inhibitor, l-nitroarginine, did not alter the responses to NC. NC
      (20 microM) elicited a marked increase in basal tone of the strips. This effect
      was less prominent after the second application of 200 microMNC or with NC-Cu
      treatment or in the presence of suramin. In anesthetized rats, during continuous
      infusion cystometry, intravesical infusion of 50 microM NC but not NC-Cu or
      cuprizone significantly decreased the intercontraction interval (ICI) without
      changing contraction amplitude. The ICI returned to normal after washout of NC.
      Suramin blocked this effect. These results indicate that NC enhances bladder
      activity by facilitating purinergic excitatory responses and that copper(I)
      sensitive mechanisms tonically inhibit purinergic transmission in the bladder.

PMID- 15501993
TI  - Facilitation of the purinergic contractile response of the guinea pig vas
      deferens by sodium orthovanadate.
AB  - Experiments were carried out to examine the effects of protein tyrosine kinase
      (PTK) and protein tyrosine phosphatase inhibitors on the purinergic contraction
      of the guinea pig vas deferens. Sodium orthovanadate (SOV) produced a robust
      increase of the amplitude of contractions evoked by both neurogenic electrical
      field stimulation and exogenous ATP. This effect of SOV was concentration- and
      time-dependent, as well as, reversible and reproducible. Genistein, a PTK
      inhibitor, but not its inactive structural analog daidzein, inhibited the SOV
      induced facilitation of the purinergic contraction. Another PTK inhibitor, 2,5
      dihydroxycinnamic acid methyl ester, which is structurally unrelated to
      genistein, also inhibited the facilitation effects of SOV. Although an
      application of as low as 3 microM of these inhibitors significantly decreased the
      effect of SOV, other PTK inhibitors, namely, butein, levandustin C, and
      thyrphostin 23, were less effective even at concentrations of 100 microM. Western
      blot experiments showed that the facilitation of the purinergic contraction by
      SOV is associated with a prominent increase in the level of tyrosine
      phosphorylation of proteins with estimated molecular sizes of 180 and 123 kDa,
      which was reversed in the presence of genistein. Evidence is also presented that
      argue against the possibility that inhibition of the Na(+)/K(+)-ATPase or
      ATPases, responsible for the clearance of ATP is involved in the SOV-induced
      facilitation of the purinergic contraction. Together, these results suggest that
      the responsiveness of the smooth muscle of the vas deferens to the actions of ATP
      is modulated via a previously unidentified mechanism, which may involve protein
      tyrosine phosphorylation.

PMID- 15501994
TI  - Impact of the cyclooxygenase system on doxorubicin-induced functional multidrug
      resistance 1 overexpression and doxorubicin sensitivity in acute myeloid leukemic
      HL-60 cells.
AB  - Multidrug resistance (MDR), a challenge in treating childhood acute myeloid
      leukemia (AML), is frequently associated with decreased drug accumulation caused
      by multidrug transporter MDR1. Doxorubicin, an important anti-AML drug, is a
      known MDR1 substrate and inducer. Its cytostatic efficacy is thus limited by MDR1
      overexpression. A recent study demonstrated cyclooxygenase-2-dependent,
      prostaglandin E(2) (PGE(2))-mediated regulation of mdr1b expression in primary
      rat hepatocyte cultures. Cyclooxygenase-2 expression is increased in several
      malignancies and considered a negative prognostic factor. Our study focused on
      cyclooxygenase system's impact on drug-induced MDR1 overexpression in AML cells.
      As a prerequisite, coexpression of MDR1 and cyclooxygenase-2 mRNA in HL-60 cells
      and primary AML blasts was demonstrated by Northern blot. Interestingly,
      incubation of AML cells with doxorubicin not only induced functionally active
      MDR1 overexpression but also mediated increased cyclooxygenase-2 mRNA and protein
      expressions with subsequent PGE(2) release (determined by flow cytometry,
      rhodamine123 efflux assay, reverse transcription-polymerase chain reaction, and
      enzyme-linked immunosorbent assay). After preincubation and subsequent parallel
      treatment with the cyclooxygenase-2-preferential inhibitor meloxicam, doxorubicin
      induced MDR1 overexpression and function were reduced (maximally at 0.1-0.5
      microM meloxicam), whereas cytostatic efficacy of doxorubicin in 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assays was
      significantly increased by up to 78 (HL-60) and 30% (AML blasts) after 72 h of
      doxorubicin treatment. In HL-60 cells, meloxicam-dependent effect on doxorubicin
      cytotoxicity was neutralized by PGE(2) preincubation. In conclusion, the
      cyclooxygenase system, especially the cyclooxygenase-2 isoform, might be involved
      in regulating doxorubicin-induced MDR1 overexpression in AML cells, with PGE(2)
      seeming to be a mediating factor. Cyclooxygenase inhibitors thus bear promise to
      overcome MDR in AML and improve therapy.

PMID- 15501995
TI  - For crying out loud: musculoskeletal assessment of inpatients referred to
      rheumatology.

PMID- 15501996
TI  - Do guidelines for the prescribing and monitoring of leflunomide need to be
      modified?

PMID- 15501997
TI  - Coronary atherosclerosis in Behcet's syndrome: a pilot study using electron-beam
      computed tomography.

PMID- 15501998
TI  - A case of reversible posterior leucoencephalopathy syndrome after rituximab
      infusion.

PMID- 15501999
TI  - Pulmonary hypertension in a patient with rheumatoid arthritis treated with
      leflunomide.

PMID- 15502000
TI  - Recurrent multifocal Mycobacterium kansasii infection in an immunosuppressed
      patient with myelodysplasia and relapsing polychondritis.

PMID- 15502001
TI  - Successful treatment of severe Raynaud's phenomenon with bosentan in four
      patients with systemic sclerosis.

PMID- 15502002
TI  - Juvenile onset spondylodiscitis: magnetic resonance imaging changes with
      infliximab.

PMID- 15502003
TI  - Infliximab treatment efficacy in lymphoedema associated with ankylosing
      spondylitis.

PMID- 15502004
TI  - Epithelioid haemangioendothelioma and paraneoplastic hypercorticism.

PMID- 15502005
TI  - Two cases of meningeal involvement in Wegener's granulomatosis.

PMID- 15502007
TI  - Metabolism, pharmacokinetics, and protein covalent binding of radiolabeled
      MaxiPost (BMS-204352) in humans.
AB  - MaxiPost [(3S)-(+)-(5-chloro-2-methoxyphenyl)-1,3-dihydro-3-fluoro-6
      (trifluoromethyl)-2H-indole-2-one); BMS-204352] is an investigational maxi-K
      channel opener to treat ischemic stroke. This study reports the disposition,
      metabolism, pharmacokinetics, and protein covalent binding of (14)C-labeled
      MaxiPost in healthy male volunteers as well as in dogs and rats. After each human
      subject received a single dose of 10 mg (14)C-labeled BMS-204352 (50 microCi) as
      a 5-ml intravenous infusion lasting 5 min, the plasma radioactivity
      concentrations showed a unique profile, wherein the concentration appeared to
      increase initially, followed by a terminal decline. The mean terminal t(1/2) of
      plasma radioactivity (259 h) was prolonged compared with that of unchanged parent
      (37 h). Furthermore, the extractability of radioactivity in plasma decreased over
      time, reaching approximately 20% at 4 h after dosing. The unextractable
      radioactivity was covalently bound to plasma proteins through a des-fluoro-des
      methyl BMS-204352 lysine adduct. Unchanged BMS-204352 and minor metabolites were
      identified in plasma extract following protein precipitation. The recovery of the
      radioactive dose in urine and feces was nearly complete in 14-day collections
      (approximately 37% in urine and 60% in feces). The N-glucuronide of the parent
      was the prominent metabolite in urine (16.5% of dose), whereas the parent was a
      major drug-related component in feces (11% of dose). Similar disposition,
      metabolism, pharmacokinetic, and protein covalent binding properties of (14)C
      labeled BMS-204352 were observed in humans, dogs, and rats.

PMID- 15502008
TI  - Analysis of substrate specificities and tissue expression of rat UDP
      glucuronosyltransferases UGT1A7 and UGT1A8.
AB  - The UGT1 complex codes for a subfamily of homologous "1A7-like" UDP
      glucuronosyltransferases (UGTs), including UGT1A7 and UGT1A8. Little information
      is available regarding either the substrate specificities or regulation of the
      UGT1A7-like forms from rats. We compared the activities and tissue expression of
      UGT1A7 and UGT1A8, which exhibit 77% identity in their amino terminal sequence.
      UGT1A7 shows broad specificity, catalyzing the glucuronidation of 31 of 40
      randomly selected substrates (100 muM) at rates >0.1 nmol/mg/min. UGT1A7
      substrates included both planar and nonplanar compounds, mono- and polycyclic
      aromatics, and compounds with bulky side chain ring substitutions. UGT1A8
      exhibited a narrower substrate specificity that completely overlapped with
      UGT1A7. UGT1A8 was most active toward the 1-OH, 4-OH, 5-OH, 6-OH, 7-OH, 10-OH, 11
      OH, and 12-OH derivatives of benzo[a]pyrene. Other effective UGT1A8 substrates
      (>0.1 nmol/mg/min) included 9-OH-benzo[a]pyrene, 1-naphthol, 4
      methylumbelliferone, 7-hydroxycoumarin, chrysin, quercetin, 4-nitrophenol, and
      estriol. In general, substrates preferred by UGT1A8 were polyaromatic planar
      structures with nonbulky substituents and a superimposable 1-naphtho ring
      structure. Studies of the tissue expression of the UGT1A7 and 1A8 mRNAs using
      RNase protection analysis suggested that each is expressed in liver and kidney of
      control rats. A major difference is the higher expression of UGT1A7 mRNA in
      intestine. These studies suggest complementary functions of the UGT1A7 and UGT1A8
      forms in xenobiotic metabolism. Further studies are necessary to determine
      whether their relative contributions change as a function of development,
      hormonal status, or exposure to inducing agents.

PMID- 15502010
TI  - Relationship between exposure and nonspecific binding of thirty-three central
      nervous system drugs in mice.
AB  - Unbound fractions in mouse brain and plasma were determined for 31 structurally
      diverse central nervous system (CNS) drugs and two active metabolites. Three
      comparisons were made between in vitro binding and in vivo exposure data, namely:
      1) mouse brain-to-plasma exposure versus unbound plasma-to-unbound brain fraction
      ratio (fu(plasma)/fu(brain)), 2) cerebrospinal fluid-to-brain exposure versus
      unbound brain fraction (fu(brain)), and 3) cerebrospinal fluid-to-plasma exposure
      versus unbound plasma fraction (fu(plasma)). Unbound fraction data were within 3
      fold of in vivo exposure ratios for the majority of the drugs examined (i.e., 22
      of 33), indicating a predominately free equilibrium across the blood-brain and
      blood-CSF barriers. Some degree of distributional impairment at either the blood
      CSF or the blood-brain barrier was indicated for 8 of the 11 remaining drugs
      (i.e., carbamazepine, midazolam, phenytoin, sulpiride, thiopental, risperidone, 9
      hydroxyrisperidone, and zolpidem). In several cases, the indicated distributional
      impairment is consistent with other independent literature reports for these
      drugs. Through the use of this approach, it appears that most CNS-active agents
      freely equilibrate across the blood-brain and blood-CSF barriers such that
      unbound drug concentrations in brain approximate those in the plasma. However,
      these results also support the intuitive concept that distributional impairment
      does not necessarily preclude CNS activity.

PMID- 15502009
TI  - The impact of P-glycoprotein on the disposition of drugs targeted for indications
      of the central nervous system: evaluation using the MDR1A/1B knockout mouse
      model.
AB  - Thirty-two structurally diverse drugs used for the treatment of various
      conditions of the central nervous system (CNS), along with two active
      metabolites, and eight non-CNS drugs were measured in brain, plasma, and
      cerebrospinal fluid in the P-glycoprotein (P-gp) knockout mouse model after
      subcutaneous administration, and the data were compared with corresponding data
      obtained in wild-type mice. Total brain-to-plasma (B/P) ratios for the CNS agents
      ranged from 0.060 to 24. Of the 34 CNS-active agents, only 7 demonstrated B/P
      area under the plasma concentration curve ratios between P-gp knockout and wild
      type mice that did not differ significantly from unity. Most of the remaining
      drugs demonstrated 1.1- to 2.6-fold greater B/P ratios in P-gp knockout mice
      versus wild-type mice. Three, risperidone, its active metabolite 9
      hydroxyrisperidone, and metoclopramide, showed marked differences in B/P ratios
      between knockout and wild-type mice (6.6- to 17-fold). Differences in B/P ratios
      and cerebrospinal fluid/plasma ratios between wild-type and knockout animals were
      correlated. Through the use of this model, it appears that most CNS-active agents
      demonstrate at least some P-gp-mediated transport that can affect brain
      concentrations. However, the impact for the majority of agents is probably minor.
      The example of risperidone illustrates that even good P-gp substrates can still
      be clinically useful CNS-active agents. However, for such agents, unbound plasma
      concentrations may need to be greater than values projected using receptor
      affinity data to achieve adequate receptor occupancy for effect.

PMID- 15502011
TI  - Regulation of glucocorticoid-inducible hydroxysteroid sulfotransferase (SULT2A
      40/41) gene transcription in primary cultured rat hepatocytes: role of
      CCAAT/enhancer-binding protein liver-enriched transcription factors.
AB  - The mechanism responsible for glucocorticoid receptor (GR)-mediated induction of
      rat hepatic hydroxysteroid sulfotransferase (SULT2A-40/41) gene transcription was
      investigated. We previously reported that the region of the SULT2A-40/41 5'
      flanking region delimited by -158 to -77 nucleotides relative to the
      transcription start site was sufficient to support GR-inducible expression. This
      region of the SULT2A-40/41 gene does not contain a consensus glucocorticoid
      receptor-responsive element, but does contain two consensus sites for liver
      enriched CCAAT/enhancer-binding protein (C/EBP) transcription factors. In the
      present study, incubation of primary cultured rat hepatocytes with a GR
      activating concentration (10(-7) M) of a potent glucocorticoid, dexamethasone or
      triamcinolone acetonide (TA), rapidly produced increases in C/EBPalpha and
      C/EBPbeta nuclear protein contents, as measured by Western blot or in vitro DNA
      binding activity analysis, that preceded increases in SULT2A-40/41 mRNA and
      protein levels. Transient cotransfection of SULT2A-40/41 reporter plasmids with a
      dominant negative C/EBP expression plasmid completely blocked TA-inducible SULT2A
      40/41 reporter gene expression. Linker scanning and site-directed mutagenesis of
      the proximal SULT2A-40/41 5'-flanking region, complemented by in vitro DNA
      binding analyses, indicated that the more distal C/EBP site was important for
      controlling SULT2A-40/41 promoter activity. These data support a role for GR
      inducible C/EBPalpha and C/EBPbeta expression in the transactivation of hepatic
      SULT2A-40/41 expression.

PMID- 15502012
TI  - Oxalate production by Sclerotinia sclerotiorum deregulates guard cells during
      infection.
AB  - Oxalic acid is a virulence factor of several phytopathogenic fungi, including
      Sclerotinia sclerotiorum (Lib.) de Bary, but the detailed mechanisms by which
      oxalic acid affects host cells and tissues are not understood. We tested the
      hypothesis that oxalate induces foliar wilting during fungal infection by
      manipulating guard cells. Unlike uninfected leaves, stomatal pores of Vicia faba
      leaves infected with S. sclerotiorum are open at night. This cellular response
      appears to be dependent on oxalic acid because stomatal pores are partially
      closed when leaves are infected with an oxalate-deficient mutant of S.
      sclerotiorum. In contrast to oxalate-deficient S. sclerotiorum, wild-type fungus
      causes an increase in stomatal conductance and transpiration as well as a
      decrease in plant biomass. Green fluorescent protein-tagged S. sclerotiorum
      emerges through open stomata from the uninfected abaxial leaf surface for
      secondary colonization. Exogenous application of oxalic acid to the detached
      abaxial epidermis of V. faba leaves induces stomatal opening. Guard cells treated
      with oxalic acid accumulate potassium and break down starch, both of which are
      known to contribute to stomatal opening. Oxalate interferes with abscisic acid
      (ABA)-induced stomatal closure. The Arabidopsis (Arabidopsis thaliana) L. Heynh.
      mutants abi1, abi3, abi4, and aba2 are more susceptible to oxalate-deficient S.
      sclerotiorum than wild-type plants, suggesting that Sclerotinia resistance is
      dependent on ABA. We conclude that oxalate acts via (1) accumulation of
      osmotically active molecules to induce stomatal opening and (2) inhibition of ABA
      induced stomatal closure.

PMID- 15502013
TI  - Zeolin. A new recombinant storage protein constructed using maize gamma-zein and
      bean phaseolin.
AB  - The major seed storage proteins of maize (Zea mays) and bean (Phaseolus
      vulgaris), zein and phaseolin, accumulate in the endoplasmic reticulum (ER) and
      in storage vacuoles, respectively. We show here that a chimeric protein composed
      of phaseolin and 89 amino acids of gamma-zein, including the repeated and the Pro
      rich domains, maintains the main characteristics of wild-type gamma-zein: It is
      insoluble unless its disulfide bonds are reduced and forms ER-located protein
      bodies. Unlike wild-type phaseolin, the protein, which we called zeolin,
      accumulates to very high amounts in leaves of transgenic tobacco (Nicotiana
      tabacum). A relevant proportion of the ER chaperone BiP is associated with zeolin
      protein bodies in an ATP-sensitive fashion. Pulse-chase labeling confirms the
      high affinity of BiP to insoluble zeolin but indicates that, unlike structurally
      defective proteins that also extensively interact with BiP, zeolin is highly
      stable. We conclude that the gamma-zein portion is sufficient to induce the
      formation of protein bodies also when fused to another protein. Because the
      storage proteins of cereals and legumes nutritionally complement each other,
      zeolin can be used as a starting point to produce nutritionally balanced and
      highly stable chimeric storage proteins.

PMID- 15502014
TI  - Evidence of programmed cell death in post-phloem transport cells of the maternal
      pedicel tissue in developing caryopsis of maize.
AB  - We present cellular- and ultracellular-level studies here to show developmental
      programmed cell death (PCD) of placento-chalazal (P-C) cell layers in maternal
      pedicel tissue in developing caryopses of normal seed (Mn1) and in the invertase
      deficient miniature (mn1) seed mutant in maize (Zea mays). PCD was evidenced by
      loss of nuclei and all subcellular membranous organizations in many P-C layers.
      The terminal deoxynucleotidyl transferase-mediated X-dUTP nick-end labeling
      (TUNEL) stain that is diagnostic of apoptotic-like PCD identified spatially and
      temporally two distinctive subdomains, which coincided with nucellar and
      integumental P-C layers based on their developmental origins. The early phase of
      PCD in the nucellar P-C was TUNEL negative and was specific to only the
      fertilized caryopses, indicating that the signaling for PCD in these maternal
      cells originated in the zygotic tissues. In fact, the initiation of PCD coincided
      with endosperm cellularization and was rapidly and coordinately completed prior
      to the beginning of the major storage phase in endosperm. Cell shape in these
      cell layers was also influenced by the genotype of filial endosperm. The later
      phase of PCD was restricted to the integumental P-C layers underneath the
      nucellar cells and was TUNEL positive in both genotypes. The two subdomains of
      the P-C layers were also distinguishable by unique cell wall-associated phenolic
      compounds. Based on collective evidence, we infer that the nucellar PCD may have
      osmolytic etiology and may lead to activation of the post-phloem transport
      function of the P-C layer, whereas the integumental PCD was senescent related, in
      particular, protecting the maturing seed against microbes that may be transported
      from the maternal tissue.

PMID- 15502015
TI  - Apoplastic binding of aluminum is involved in silicon-induced amelioration of
      aluminum toxicity in maize.
AB  - The alleviating effect of silicon (Si) supply on aluminum (Al) toxicity was
      suggested to be based on ex or in planta mechanisms. In our experiments with the
      Al-sensitive maize (Zea mays) cultivar Lixis, Si treatment but not Si
      pretreatment ameliorated Al-induced root injury as revealed by less root-growth
      inhibition and callose formation. Si treatment did not affect monomeric Al
      concentrations in the nutrient solution, suggesting an in planta effect of Si on
      Al resistance. A fractionated analysis of Si and Al in the 1-cm root apices
      revealed that more than 85% of the root-tip Al was bound in the cell wall. Al
      contents in the apoplastic sap, the symplastic sap, and the cell wall did not
      differ between -Si and +Si plants. Si did not affect the Al-induced exudation of
      organic acid anions and phenols from the root apices. However, Al treatment
      greatly enhanced Si accumulation in the cell wall fraction, reducing the mobility
      of apoplastic Al. From our data we conclude that Si treatment leads to the
      formation of hydroxyaluminumsilicates in the apoplast of the root apex, thus
      detoxifying Al.

PMID- 15502016
TI  - Endobronchial hemorrhage due to pulmonary circulation tear: separating the lungs
      and the air from the blood.

PMID- 15502017
TI  - Treatment of severe pulmonary hemorrhage after cardiopulmonary bypass by
      selective, temporary balloon occlusion.
AB  - Severe pulmonary bleeding causes frequent mortality, particularly if this event
      occurs during separation from extracorporeal circulation during cardiac surgery.
      We present a new approach to treat this life-threatening complication: temporary
      balloon occlusion of the pulmonary artery feeding the involved lobe. On
      attempting to wean a 71-yr-old female patient from cardiopulmonary bypass after
      aortic valve replacement, she lost more than 2 L of blood through her trachea
      over approximately 15 min and severe gas embolism into the left atrium was
      visualized on transesophageal echocardiography. As the bleeding was too vigorous
      to be localized by fiberoptic bronchoscopy, an interventional cardiologist was
      consulted. After localizing the affected lobe using fluoroscopy, he inflated a
      balloon dilating catheter in the lower lobe artery. This effectively stopped the
      bleeding. Separation from extracorporeal circulation was uneventful using one
      lung ventilation to prevent further gas embolism. Sixteen hours after the end of
      surgery the catheter could be deflated and removed without any further
      intervention. The patient made an excellent recovery.

PMID- 15502018
TI  - The effects of argatroban on thrombin generation and hemostatic activation in
      vitro.
AB  - We evaluated argatroban, a direct thrombin inhibitor, as a heparin adjunct for
      anticoagulation. Platelet-poor plasma (PPP) was isolated from blood collected
      from 12 volunteers. Thrombin generation measurements were performed in donor PPP
      that was mixed with antithrombin (AT)-poor plasma to yield AT levels of 0%, 20%,
      60%, and 100%. Effects of argatroban (0-1.0 microg/mL), heparin (0.25 U/mL), or
      the combination of argatroban (0.5 microg/mL) and heparin were also studied. The
      addition of increasing concentrations of argatroban, heparin, or both to donor
      PPP (AT level approximately 100%) caused progressive decreases in the lag time
      and peak formation of thrombin generation. Heparin (0.25 U/mL) at small AT
      concentrations had a minimal effect on lag time or peak thrombin formation; its
      effectiveness of inhibiting thrombin was directly correlated with the
      concentration of AT. Argatroban at 0.5 microg/mL was effective in decreasing
      thrombin formation at both low and normal AT levels, but it was most effective
      when combined with heparin. Additionally, blood samples were obtained from 47
      cardiac surgical patients, and the interaction of heparin (>1.5 U/mL) and AT or
      argatroban on clot formation was evaluated with kaolin activated clotting times
      (ACTs). Significant increases of ACTs at all heparin levels were observed with
      the addition of argatroban (0.125 and 0.25 microg/mL). The addition of AT (0.2
      U/mL) to heparinized blood samples further prolonged ACTs. In summary, we showed
      that argatroban, unlike heparin, could effectively reduce thrombin generation
      regardless of AT levels and could prolong ACTs in vitro at clinically used
      concentrations.

PMID- 15502019
TI  - A novel thrombelastograph tissue factor/kaolin assay of activated clotting times
      for monitoring heparin anticoagulation during cardiopulmonary bypass.
AB  - We used a thrombelastograph (TEG) assay with tissue factor and kaolin (TEG TF/K)
      to measure activated clotting time (ACT) in 31 patients during cardiopulmonary
      bypass. For comparison, ACTs were also determined by a Hemochron Jr. Signature
      and a Hepcon HMS. The TEG TF/K correlated with both the Hepcon (r(2) = 0.789) and
      Hemochron (r(2) = 0.743) ACTs. The average ACT after heparin was 319 +/- 119 s
      (mean +/- sd) for the TEG TF/K compared with 624 +/- 118 s for the Hepcon
      instrument. To evaluate the effects of hemodilution on TEG TF/K and Hemochron
      assays, ACT assays were performed on blood diluted to 50% and titrated with
      heparin from 0 to 6 U/mL. Both instruments showed significant (P < 0.01) changes
      in the ACT-versus-heparin slope, but the 0 heparin intercept for the TEG TF/K
      ACTs was not significantly changed (P = 0.292), in contrast to that for the
      Hemochron device (P = 0.041). Both instruments also indicated the same 1.3:1
      ratio of protamine to heparin for optimum heparin neutralization, with increasing
      ACTs at ratios >2.6:1. The TEG TF/K ACT assay rapidly monitors heparin
      anticoagulation, in addition to the capabilities of this instrument to monitor
      platelet function, clotting factors, and fibrinolysis.

PMID- 15502020
TI  - S(+)-ketamine as an analgesic adjunct reduces opioid consumption after cardiac
      surgery.
AB  - There are no studies evaluating S(+)-ketamine for pain management after
      sternotomy. In this prospective, randomized, double-blind, placebo-controlled
      clinical trial, we evaluated the efficacy and feasibility of S(+)-ketamine as an
      adjunctive analgesic after cardiac surgery. Ninety patients scheduled for
      elective coronary artery bypass grafting (CABG) were randomized to receive either
      a 75 microg/kg bolus of S(+)-ketamine followed by a continuous infusion of 1.25
      microg . kg(-1) . min(-1) for 48 h (n = 44) or placebo (normal saline bolus and
      infusion) (n = 46). From the time of tracheal extubation, patients could access
      an opioid (oxycodone) via a patient-controlled analgesia device, and the
      cumulative oxycodone doses were measured over 48 h. Pain was evaluated on a
      visual analog scale three times daily. The quality of recovery, patient
      satisfaction with pain management, and adverse effects were recorded. The
      cumulative oxycodone consumption during the first 48 postoperative hours was less
      in the S(+)-ketamine group (103 +/- 44 mg) than in the placebo group (125 +/- 45
      mg; mean difference, 22 mg; 95% confidence interval for the difference, 3-40 mg;
      P = 0.023). Pain scores did not differ between the groups at rest (P = 0.17) or
      during a deep breath (P = 0.23). Patient satisfaction was superior in S(+)
      ketamine-treated patients: 26 (60%) of 44 in the S(+)-ketamine group compared
      with 16 (35%) of 46 in the placebo group were very satisfied with the analgesic
      management (P = 0.032). Nausea and vomiting were the most common adverse events,
      with similar frequencies in both groups. Four patients in the S(+)-ketamine group
      developed transient hallucinations during the infusion, versus none in the
      placebo group. In conclusion, small-dose S(+)-ketamine decreased opioid
      consumption in CABG patients during the first 48 h after surgery.

PMID- 15502021
TI  - The impact of isoflurane during simulated ischemia/reoxygenation on intracellular
      calcium, contractile function, and arrhythmia in ventricular myocytes.
AB  - Some of isoflurane's cellular actions, such as interference with intracellular
      Ca(2+) handling, inhibition of the respiratory chain, and the capability to
      produce oxygen radicals, could result in impaired cellular function during
      ischemia/reoxygenation (I/R). We investigated the effects of isoflurane applied
      during I/R on intracellular Ca(2+), oxygen radical formation, arrhythmic events,
      and contractile function in rat cardiomyocytes. Single ventricular myocytes were
      subjected to 30 min of simulated ischemia followed by 30 min of reoxygenation.
      After baseline measurements, isoflurane-treated cells were exposed to 1 minimum
      alveolar concentration of isoflurane in air, whereas control cells were exposed
      to air only. Cytosolic Ca(2+) overload was observed in the isoflurane group (P <
      0.05). During ischemia, systolic cell shortening decreased in both groups. In the
      isoflurane group, arrhythmic events and hypercontracture occurred more often
      during I/R, and the recovery of contractility during reoxygenation was less
      marked (P < 0.05). Furthermore, increased oxygen radical generation was detected
      in isoflurane-treated myocytes during reoxygenation (P < 0.05). Isoflurane given
      during I/R in this study induced intracellular Ca(2+) accumulation and impaired
      cell function. These potentially harmful effects were associated with a
      diminished Ca(2+) clearance and an accelerated oxygen radical production.

PMID- 15502022
TI  - Preconditioning by isoflurane is mediated by reactive oxygen species generated
      from mitochondrial electron transport chain complex III.
AB  - Reactive oxygen species (ROS) mediate volatile anesthetic preconditioning. We
      tested the hypothesis that isoflurane (ISO) generates ROS from electron transport
      chain complexes I and III. Rabbits (n = 55) underwent 30 min coronary artery
      occlusion followed by 3 h reperfusion and received 0.9% saline, the complex I
      inhibitor diphenyleneiodonium (DPI; 1.5 mg/kg bolus followed by 1.5 mg/kg over 1
      h), or the complex III inhibitor myxothiazol (MYX; 0.1 mg/kg bolus followed by
      0.3 mg/kg over 1 h) in the absence and presence of 1.0 minimum alveolar
      concentration ISO. ISO was administered for 30 min and discontinued 15 min before
      coronary occlusion. Infarct size and ROS production (n = 32) were determined
      using triphenyltetrazolium staining and ethidium-DNA fluorescence, respectively.
      Adenosine triphosphate (ATP) synthesis in mitochondria obtained from rabbit
      hearts (n = 24) subjected to drug interventions was measured by luciferin
      luciferase luminometry. ISO significantly (P < 0.05) reduced infarct size (19% +/
      4%) as compared with control (39% +/- 4%). MYX (35% +/- 4%), but not DPI (24% +/
      2%), abolished this protection. ISO increased ethidium-DNA fluorescence (83 +/-
      11 U) as compared with control (40 +/- 12 U). MYX (35 +/- 3 U), but not DPI (78
      +/- 9 U), abolished ROS generation. DPI and MYX selectively reduced complex I-
      and complex III-mediated ATP synthesis, respectively. ROS generated from electron
      transport chain complex III mediate ISO-induced cardioprotection.

PMID- 15502023
TI  - Protein kinase C inhibitors produce mitochondrial flavoprotein oxidation in
      cardiac myocytes.
AB  - Inhibition of protein kinase C (PKC) antagonizes ischemic preconditioning of
      myocardium. Opening of mitochondrial adenosine triphosphate (ATP)-dependent
      potassium (mitoK(ATP)) channels and subsequent oxidation of mitochondria are
      known to contribute to ischemic preconditioning. We therefore tested the effects
      of PKC inhibitors on flavoprotein oxidation, measured by flavoprotein
      fluorescence, as an index of mitoK(ATP) activity in ventricular myocytes from
      guinea pigs. The PKC inhibitors chelerythrine (1 and 5 microM) and
      bisindolylmaleimide (100 and 400 nM) strongly increased flavoprotein oxidation in
      a dose-dependent manner. Specific inhibition of PKC-delta by rottlerin produced
      persistent flavoprotein oxidation. Inhibition of the production of inositol
      (1,4,5)-triphosphate by neomycin (0.5 mM) abolished chelerythrine- but not
      rottlerin-induced flavoprotein oxidation. Inhibition of PKC promotes flavoprotein
      oxidation via production of inositol (1,4,5)-triphosphate, possibly through the
      PKC-delta isoform. We speculate that although a certain degree of mitochondrial
      flavoprotein oxidation causes cardioprotective effects, excessive and/or
      persistent oxidation abolishes any beneficial actions. Instead of a simple
      mediator, PKC may act as a regulator of the mitoK(ATP) channel to prevent
      excessive mitochondrial oxidation.

PMID- 15502024
TI  - The effect of apolipoprotein E genotype on neuron specific enolase and S-100beta
      levels after cardiac surgery.
AB  - We tested the hypothesis that two biochemical markers of brain injury would be
      increased after cardiac surgery in patients with the apolipoprotein (Apo)
      epsilon4 allele. Arterial blood samples were drawn before and 8 and 24 h after
      induction of anesthesia and later assayed for neuron specific enolase (NSE), S
      100beta, and apoE genotype. There was a highly significant temporal effect with
      increases in NSE (2.2 +/- 1.6 ng/L to 11.8 +/- 8.9 ng/L; P < 0.0001) (mean +/-
      sd) and S-100beta (0.15 +/- 0.1 microg/L to 0.45 +/- 0.42 microg/L, P < 0.0001).
      At 8 and 24 h after induction of anesthesia S-100beta (0.28 +/- 0.18 microg/L
      versus 0.91 +/- 0.54 microg/L; P =0.004) and NSE (8.6 +/- 5.6 ng/L versus 19.0 +/
      19.7 ng/L; P = 0.02) levels, respectively, were higher in patients with the
      Apoepsilon4 allele. Patients with the Apoepsilon4 allele may be more susceptible
      to perioperative neural insults.

PMID- 15502025
TI  - A perioperative echocardiographic reporting and recording system.
AB  - Advances in video capture, compression, and streaming technology, coupled with
      improvements in central processing unit design and the inclusion of a database
      engine in the Windows operating system, have simplified the task of implementing
      a digital echocardiographic recording system. I describe an application that uses
      these technologies and runs on a notebook computer.

PMID- 15502026
TI  - Is muscle relaxant necessary for cardiac surgery?
AB  - The need for continuous and complete paralysis during the entire cardiac surgery
      has not yet been investigated and is still controversial. In a series of 87
      patients undergoing cardiac surgery with normothermic cardiopulmonary bypass, we
      studied the delay of recovery, incidence of residual paralysis, unwanted patient
      movement, and difficult surgical conditions after a single dose of atracurium
      (0.5 mg/kg) or cisatracurium (0.15 mg/kg). Anesthesia was induced with etomidate
      and remifentanil followed by tracheal intubation. The delay to obtain a train-of
      four ratio of >0.9 was longer with cisatracurium than with atracurium (86 +/- 18
      versus 97 +/- 19 min). However, at the end of surgery, this ratio was >0.9 for
      all patients. The presence of unwanted patient movement, diaphragmatic
      contractions, and difficult surgical conditions were observed. Delay of
      extubation of the trachea was similar in both groups. We conclude that there is
      no need for continuous neuromuscular blockade during cardiac surgery. A single
      dose of either atracurium or cisatracurium is sufficient to provide efficient
      paralysis from the start of induction leading to quicker recovery from paralysis
      in fast-track cardiac surgery.

PMID- 15502027
TI  - The effects of propofol, small-dose isoflurane, and nitrous oxide on cortical
      somatosensory evoked potential and bispectral index monitoring in adolescents
      undergoing spinal fusion.
AB  - In this study we compared the effects of propofol, small-dose isoflurane, and
      nitrous oxide (N(2)O) on cortical somatosensory evoked potentials (SSEP) and
      bispectral index (BIS) monitoring in adolescents undergoing spinal fusion. Twelve
      patients received the following anesthetic maintenance combinations in a randomly
      determined order: treatment #1: isoflurane 0.4% + N(2)O 70% + O(2) 30%; treatment
      #2: isoflurane 0.6% + N(2)O 70% + O(2) 30%; treatment #3: isoflurane 0.6% + air +
      O(2) 30%; treatment #4: propofol 120 microg . kg(-1) . min(-1) + air + O(2) 30%.
      Cortical SSEP amplitudes measured during anesthesia maintenance with treatment #3
      (isoflurane 0.6%/air) were more than those measured during maintenance with
      treatment #1 (isoflurane 0.4%/N(2)O 70%) (P < 0.0001) and treatment #2
      (isoflurane 0.6%/N(2)O 70%) (P < 0.0052). Cortical SSEP amplitudes measured
      during treatment #4 (propofol 120 microg . kg(-1) . min(-1)/air) were more than
      treatment #1 (isoflurane 0.4%/N(2)O 70%) (P < 0.0001), treatment #2 (Iso
      0.6%/N(2)O 70%) (P < 0.0007), and treatment #3 (isoflurane 0.6%/air) (P <
      0.0191). In addition, average BIS values measured during treatments 1, 2, 3 and 4
      were 62, 62, 61, and 44 respectively. Only treatment #4 (propofol 120 microg .
      kg(-1) . min(-1)/air) uniformly maintained BIS values less than 60. Our study
      demonstrates that propofol better preserves cortical SSEP amplitude measurement
      and provides a deeper level of hypnosis as measured by BIS values than
      combinations of small-dose isoflurane/N(2)O or small-dose isoflurane alone.

PMID- 15502028
TI  - Fibrinogen in children undergoing cardiac surgery: is it effective?
AB  - There is speculation based on laboratory tests and biochemical data regarding the
      functional integrity of the fibrinogen in young children. Recent investigations
      in adults have demonstrated that their fibrinogen level correlates with the
      thromboelastogram maximum amplitude (MA) after modification with a glycoprotein
      IIb/IIIa receptor blocker that uncouples platelet-fibrinogen interactions. We
      postulate that if the fibrinogen of young children is functionally intact then
      their fibrinogen levels should also correlate with modified thromboelastogram MA
      values as they do in adults. We compared modified and unmodified
      thromboelastogram variables of 250 children <2 yr old undergoing cardiac surgery
      with their fibrinogen levels and platelet counts. Five age groups were
      distinguished to determine if and when correlations become significant (<1 mo, 1
      3 mo, 3-6 mo, 6-12 mo, and 12-24 mo). Fibrinogen levels correlated with modified
      thromboelastogram MAs only in the 12-24 mo group. In this 12-24 mo age group
      other correlations between fibrinogen levels and thromboelastogram variables
      influenced by fibrinogen also became significant, as did correlations noted in
      adults between platelet counts and thromboelastogram variables. We conclude that
      the fibrinogen of children <12 mo old with congenital heart disease is
      qualitatively dysfunctional.

PMID- 15502029
TI  - The pharmacokinetics of the intravenous formulation of fentanyl citrate
      administered orally in children undergoing general anesthesia.
AB  - The bioavailability of oral transmucosal fentanyl citrate (OTFC) in children is
      similar to that of fentanyl solution administered orally to adults. We
      hypothesized that administering an oral fentanyl solution to children would
      result in similar fentanyl plasma concentrations and pharmacokinetic variables as
      administering comparable doses of OTFC. In this pilot study, 10 healthy children
      requiring postoperative analgesia were enrolled. Each received the undiluted IV
      fentanyl formulation orally (approximately 10-15 microg/kg; maximum, 400 microg).
      Venous blood samples were collected from 15 to 600 min after administration.
      Pharmacokinetic variables were determined using noncompartmental analysis and
      were compared with a previously studied population of children who received a
      similar dose of OTFC. Pharmacokinetic variables for the orally administered IV
      fentanyl formulation were as follows: time to reach peak concentration = 1.7 +/-
      1.6 h, peak concentration = 1.83 +/- 1.19 ng/mL, half-life = 4.7 +/- 2.8 h, area
      under the plasma concentration time curve = 6.46 +/- 3.96 h . ng(-1) . mL(-1),
      apparent oral volume of distribution (V/F) = 17.5 +/- 7.2 L/kg, apparent oral
      clearance (CL/F) = 3.33 +/- 2.25 L . kg(-1) . h(-1). Although both OTFC and
      orally administered IV fentanyl resulted in similar pharmacokinetic variables and
      plasma concentrations for a given dose, there was marked interpatient
      variability, particularly in the early hours after oral administration of the IV
      formulation of fentanyl. This suggests that this method of administration be used
      with caution until further data are available.

PMID- 15502030
TI  - A secure method of nasotracheal tube fixation using an infant feeding tube.
AB  - A well secured endotracheal tube is very essential for the safe conduct of
      anesthesia. In maxillofacial surgeries, providing secure fixation of the
      nasotracheal tube has always been a problem. We have used an infant feeding tube
      that goes around the nasal septum for the fixation of the nasal endotracheal
      tube. This method of securing the nasotracheal tube does not hinder the surgical
      access, is well tolerated by patients, and is safe.

PMID- 15502031
TI  - Review of pediatric sedation.
AB  - Sedating children for diagnostic and therapeutic procedures remains an area of
      rapid change and considerable controversy. Exploration of this topic is made
      difficult by the fact that the reports of techniques and outcomes for pediatric
      sedation appear in a wide range of subspecialty publications and rarely undergo
      comprehensive examination. In this review article, we will touch on many aspects
      of the topic of pediatric sedation from the perspective of the anesthesiologist.
      We begin with a review of the historical role of anesthesiologists in the
      development of the current standards for pediatric sedation. We also examine the
      current status of pediatric sedation as reflected in published studies and
      reports. A specific review of the issues surrounding safety of sedation services
      is included. Current trends in sedation practice, including the expanding role of
      potent sedative hypnotic drugs outside the field of anesthesiology, are noted.
      Finally, we suggest future areas for research and clinical improvement for
      sedation providers.

PMID- 15502032
TI  - Neurological monitoring for congenital heart surgery.
AB  - The incidence of neurological complications after pediatric cardiac surgery
      ranges from 2% to 25%. The causes are multifactorial and include preoperative
      brain malformations, perioperative hypoxemia and low cardiac output states,
      sequelae of cardiopulmonary bypass, and deep hypothermic circulatory arrest.
      Neurological monitoring devices are readily available and the anesthesiologist
      can now monitor the brain during pediatric cardiac surgery. In this review we
      discuss near-infrared cerebral oximetry, transcranial Doppler ultrasound, and
      electroencephalographic monitors for use during congenital heart surgery. After
      review of the basic principles of each monitoring modality, we discuss their uses
      during pediatric heart surgery. We present evidence that multimodal neurological
      monitoring in conjunction with a treatment algorithm may improve neurological
      outcome for patients undergoing congenital heart surgery and present one such
      algorithm.

PMID- 15502033
TI  - Suspected central anticholinergic syndrome in a 6-week-old infant.
AB  - A 6-wk-old male infant became unresponsive after an uneventful general anesthetic
      for hernia repair. His symptoms were consistent with central anticholinergic
      syndrome. He appeared to awaken after treatment with IV physostigmine in a dose
      of 0.04 mg/kg. Because of the recurrence of sedation, a second physostigmine
      infusion was administered, which again led to transient arousal. Finally, the
      patient awoke spontaneously after 24 h and recovered uneventfully.

PMID- 15502034
TI  - A multiple-dose phase I study of intranasal hydromorphone hydrochloride in
      healthy volunteers.
AB  - We evaluated the pharmacokinetics, tolerability, and safety of 1 and 2 mg of
      intranasal hydromorphone hydrochloride in an open-label, single- and multiple
      dose study. This Phase I study was conducted in 24 healthy volunteers (13 men and
      11 women). Intranasal doses were delivered as 0.1-mL metered-dose sprays into one
      or both nostrils for 1- and 2-mg doses, respectively. Venous blood samples were
      taken serially from 0 to 12 h after the first single dose and the last (seventh)
      multiple dose. Plasma hydromorphone concentrations were determined by liquid
      chromatography/mass spectrometry/mass spectrometry. Noncompartmental analysis was
      used to estimate pharmacokinetic variables. After 7 intranasal doses of 1 and 2
      mg (once every 6 h), mean +/- sd peak plasma concentrations of 2.8 +/- 0.7 ng/mL
      and 5.3 +/- 2.3 ng/mL, respectively, were observed. The median time to peak
      concentration was 20 min for both single and multiple doses. Dose proportionality
      was observed for the 1- and 2-mg doses. Adverse events included somnolence,
      dizziness, and bad taste after dose administration. Intranasal hydromorphone
      hydrochloride was well tolerated and demonstrated rapid nasal drug absorption and
      predictable accumulation. These results support clinical investigation of
      hydromorphone hydrochloride nasal spray for use as an alternative to oral and IM
      administration.

PMID- 15502035
TI  - A prospective, randomized, double-blind comparison of unilateral spinal
      anesthesia with hyperbaric bupivacaine, ropivacaine, or levobupivacaine for
      inguinal herniorrhaphy.
AB  - In 60 patients undergoing inguinal hernia repair, we compared the clinical
      profile of unilateral spinal anesthesia produced with either 8 mg of hyperbaric
      bupivacaine 0.5% (n = 20), 8 mg of hyperbaric levobupivacaine 0.5% (n = 20), or
      12 mg of hyperbaric ropivacaine 0.5% (n = 20). The study drug was injected slowly
      through a 25-gauge Whitacre directional needle and patients maintained the
      lateral decubitus position for 15 min. The onset time and intraoperative efficacy
      were similar in the three groups. The maximal level of sensory block on the
      operative and nonoperative sides was T6 (T12-5) and L3 (/[no sensory level
      detectable]-T4) with bupivacaine, T8 (T12-5) and L3 (/-T3) with levobupivacaine,
      T5 (T10-2) and T11 (/-T3) with ropivacaine (P = 0.11, P = 0.23, respectively).
      Complete regression of spinal anesthesia occurred after 166 +/- 42 min with
      ropivacaine, 210 +/- 63 min with levobupivacaine, and 190 +/- 51 min with
      bupivacaine (P = 0.03 and P = 0.04, respectively); however, no differences were
      observed in time for home discharge (329 +/- 89 min with bupivacaine, 261 +/- 112
      min with levobupivacaine, and 332 +/- 57 min with ropivacaine [P = 0.28]). We
      conclude that 8 mg of levobupivacaine or 12 mg of ropivacaine are acceptable
      alternatives to 8 mg of bupivacaine when limiting spinal block at the operative
      side for inguinal hernia repair.

PMID- 15502036
TI  - Impaired acquisition of spatial memory 2 weeks after isoflurane and isoflurane
      nitrous oxide anesthesia in aged rats.
AB  - Aged rats are impaired on a spatial memory task for at least 24-48 h after
      isoflurane-nitrous oxide anesthesia. In this study, we tested how long the
      impairment lasts and investigated the role of nitrous oxide. Eighteen-month-old
      rats were randomized to anesthesia for 2 h with 1.2% isoflurane with or without
      70% nitrous oxide or a control group (30% oxygen). Two weeks later, rats were
      tested daily for 14 days on a 12-arm radial maze. The number of correct choices
      to first error, total errors, and time to complete the maze were recorded. Rats
      anesthetized with 1.2% isoflurane with 70% nitrous oxide made fewer correct
      choices before first error (P < or = 0.05). Trends toward similar results were
      noted for error rate and time to complete the maze, but these did not achieve
      statistical significance. Post hoc analysis comparing all anesthetized rats to
      controls demonstrated that anesthetized rats made fewer correct choices to first
      error (P < or = 0.05) and took longer to complete the maze (P <or = 0.05). There
      were no differences in total number of errors (P < or = 0.06). Thus, spatial
      memory is impaired for 2 wk after general anesthesia in aged rats independent of
      whether nitrous oxide is used.

PMID- 15502037
TI  - Xenon does not prolong neuromuscular block of rocuronium.
AB  - With the exception of xenon, the interaction between muscle relaxants and inhaled
      anesthetics is known. We therefore compared the pharmacodynamics of rocuronium
      during xenon anesthesia versus a total IV anesthesia with propofol. Anesthesia
      was induced with propofol and remifentanil in both the xenon and propofol groups
      (each n = 20). The xenon group received xenon via face mask until an end
      expiratory concentration of 60% was maintained for 1 min. Meanwhile, the
      acceleromyograph (TOF-Watch SX(R)) was calibrated and a frequent train-of-four
      stimulation of the musculus adductor pollicis was started. After stabilization of
      the signal for 5 min, a single bolus of 0.6 mg/kg rocuronium was injected.
      Anesthesia was maintained with xenon and remifentanil (xenon group) or with
      propofol and remifentanil (propofol group). There were no significant differences
      between the groups concerning the onset time (xenon group 125 +/- 33 and propofol
      group 144 +/- 43 s), duration (xenon group 33.2 +/- 10.8 and propofol group 32.6
      +/- 8.4 min), recovery index (xenon group 9.4 +/- 6.6 and propofol group 8.4 +/-
      5.3 min), and clinical recovery (xenon group 18.0 +/- 10.2 and propofol group
      17.1 +/- 8.5 min). We conclude that the neuromuscular blocking effects of
      rocuronium are not different when given during propofol versus xenon anesthesia.

PMID- 15502038
TI  - Different F-wave recovery after neuromuscular blockade with pancuronium and
      mivacurium.
AB  - We performed this study to assess the recovery period after neuromuscular
      blockade by electromyographic F-wave analysis, a method that supplies more
      information about more proximal parts of the motor system than conventionally
      used methods, e.g., mechanomyography (MMG). In 20 neurosurgical ASA physical
      status I or II patients anesthesia was induced and maintained with IV fentanyl
      and midazolam. Patients were randomly assigned to receive either 0.25 mg/kg
      mivacurium (MV group, n = 10) or 0.1 mg/kg pancuronium (PC group, n = 10)
      intraoperatively. MMG monitoring of the adductor pollicis muscle was performed
      continuously. F waves were recorded at the abductor pollicis muscle of the
      contralateral hand at train-of-four (TOF) ratios of 0.1, 0.25, 0.5, 0.7, 0.75,
      0.8, 0.85, 0.9, and 0.95. Recovery of F-wave amplitudes after neuromuscular
      blockade with pancuronium was significantly slower compared with mivacurium (P =
      0.004) during the clinically important recovery period defined by MMG TOF ratios
      from 0.7 to 0.95. This electrophysiologic finding suggests a differential
      recovery of the motor system after administration of pancuronium and mivacurium
      not detected by MMG.

PMID- 15502039
TI  - The inhibition of aortic smooth muscle cell proliferation by the intravenous
      anesthetic ketamine.
AB  - Smooth muscle cell (SMC) proliferation has been recognized as central to the
      pathology of both major forms of vascular disease, atherosclerosis and
      hypertension. Recently, we reported that ketamine inhibits rat mesangial cell
      proliferation, suggesting that ketamine inhibits cell growth. Although the IV
      anesthetic ketamine has been widely used clinically, the exact effects of
      ketamine on vascular SMC proliferation have not been studied. In this study, we
      investigated the effects of ketamine on vascular SMC proliferation. Ketamine
      inhibited [(3)H]thymidine incorporation and decreased the number of SMCs in a
      concentration-dependent manner (10-200 microM); neither propofol nor fentanyl
      inhibited [(3)H]thymidine incorporation into human aortic SMCs. The protein
      kinase C (PKC) inhibitor GF109203x abolished the ketamine-induced inhibition of
      [(3)H]thymidine incorporation into SMC, but the inhibition was not affected by
      either the protein kinase A inhibitor H-89 or the protein kinase G inhibitor
      KT5823. A histological analysis demonstrated the inhibitory effect of ketamine on
      the intimal thickening of the balloon-injured rat aorta. Based on these results,
      ketamine inhibits SMCs at clinical concentrations via the PKC pathway. Our
      results indicate that ketamine might prevent the proliferation of SMCs
      clinically.

PMID- 15502040
TI  - Isoflurane depresses windup of C fiber-evoked limb withdrawal with variable
      effects on nociceptive lumbar spinal neurons in rats.
AB  - Windup is a progressive increase in responses of nociceptive spinal cord neurons
      to repeated electrical C fiber stimulation. We hypothesized that isoflurane would
      depress windup at approximately the minimum alveolar anesthetic concentration
      (MAC) required to suppress purposeful movement in response to noxious
      stimulation. We recorded windup responses in single lumbar spinal neurons (n =
      17) to a series of 15 repetitive electrical stimuli delivered at 1 Hz to the
      hindpaw at C fiber strength; hindpaw withdrawal force was simultaneously
      recorded. The total number of action potentials per 15 stimuli (mean +/- sem as a
      percentage of each neuron's maximal response) was 83% +/- 5%, 84% +/- 5%, 67% +/-
      7%, and 57% +/- 8% at 0.7, 0.9, 1.1, and 1.4 MAC, respectively. The 0.9 and 1.1
      MAC values differed significantly from each other, whereas the 0.7 and 0.9 MAC
      values differed from the 1.4 MAC value (P < 0.05). The reduced firing was
      attributed to a depression of the initial C fiber-evoked responses in most units,
      and a reduction in windup slope over the initial 5 stimuli in 6 units. Muscle
      force was 67%, 11%, and 4% of the 0.7 MAC value at 0.9, 1.1, and 1.4 MAC,
      respectively. Isoflurane depressed excitability and variably affected windup of
      lumbar spinal cord neurons, while uniformly depressing windup of limb withdrawals
      in a concentration-dependent manner.

PMID- 15502041
TI  - Sevoflurane and propofol increase 11C-flumazenil binding to gamma-aminobutyric
      acidA receptors in humans.
AB  - Based on in vitro studies and animal data, most anesthetics are supposed to act
      via gamma-aminobutyric acid type A (GABA(A)) receptors. However, this fundamental
      characteristic has not been extensively investigated in humans. We studied (11)C
      flumazenil binding to GABA(A) receptors during sevoflurane and propofol
      anesthesia in the living human brain using positron emission tomography (PET).
      Fourteen healthy male subjects underwent 2 60-min dynamic PET studies with (11)C
      labeled flumazenil, awake and during anesthesia. Anesthesia was maintained with
      2% end-tidal sevoflurane (n = 7) or propofol at a target plasma concentration of
      9.0 +/- 3.0 (mean +/- sd) microg/mL (n = 7). The depth of anesthesia was measured
      with bispectral index (BIS). Values of regional distribution volumes (DV) of
      (11)C-flumazenil were calculated in several brain areas using metabolite
      corrected arterial plasma curves and a two-compartment model. Separate voxel
      based statistical analysis using parametric DV images was performed for detailed
      visualization. The average BIS index was 35 +/- 6 in the sevoflurane group and 28
      +/- 8 in the propofol group (P = 0.02). Sevoflurane increased the DV of (11)C
      flumazenil significantly (P < 0.05) in all brain areas studied except the pons
      and the white matter. In the propofol group the increases were significant (P <
      0.05) in the caudatus, putamen, cerebellum, thalamus and the frontal, temporal,
      and parietal cortices. Furthermore, the DV increases in the frontal, occipital,
      parietal, and temporal cortical areas and in the putamen were statistically
      significantly larger in the sevoflurane than in the propofol group. Our findings
      support the involvement of GABA(A) receptors in the mechanism of action of both
      anesthetics in humans.

PMID- 15502042
TI  - Hypoglycemia associated with preoperative metoprolol administration.
AB  - Perioperative beta(1)-selective-adrenergic antagonist administration has been
      shown to decrease morbidity and mortality in patients with cardiac disease
      undergoing surgical procedures. We report a case of a patient receiving the
      selective beta(1)-adrenergic antagonist, metoprolol, immediately before surgery
      that was associated with severe hypoglycemia. We postulate that an underlying
      abnormality in energy requirements or metabolism may allow for beta(1)-selective
      adrenergic antagonists to precipitate hypoglycemia.

PMID- 15502043
TI  - Is the patient state analyzer with the PSArray2 a cost-effective alternative to
      the bispectral index monitor during the perioperative period?
AB  - New disposable electrodes, the PSArray and XP sensor, have been developed for the
      patient state analyzer (PSA) and the bispectral index (BIS) monitors,
      respectively. We designed this clinical study to compare the sensitivity and
      specificity of the patient state index (PSI) with the BIS during the
      perioperative period when the new electrode sensors were used. Twenty-two
      consenting patients scheduled for elective laparoscopic procedures were enrolled
      in this prospective study. The elapsed time to apply electrodes and obtain a
      baseline index value was recorded, as were the comparative PSI and BIS values at
      specific time intervals during the induction, maintenance, and emergence periods
      in patients who were administered a standardized general anesthetic. In addition,
      the changes in these indices were recorded after a bolus dose of propofol (20 mg
      IV) or a 2% increase or decrease in the inspired concentration of desflurane
      during the maintenance period. The total elapsed time to obtain an index value
      was similar with both devices (66 +/- 32 s versus 72 +/- 41 s for the PSA and
      BIS, respectively). By using logistic regression models, both the BIS and PSI
      were found to be equally effective as predictors of unconsciousness (i.e.,
      failure to respond to verbal stimuli). The PSI also correlated with the BIS
      during both the induction of (R = 0.85) and the emergence from (R = 0.74) general
      anesthesia. The area under the receiver operating characteristic curve for
      detection of consciousness also indicated a similar performance with the PSI
      (0.98 +/- 0.05) and the BIS (0.97 +/- 0.05). During the maintenance period, the
      PSI values tended to be lower than the BIS value; however, the responses to
      changes in propofol and desflurane were similar. Finally, the PSI (versus BIS)
      values showed less interference from the electrocautery unit during the operation
      (31% versus 73%, respectively). Although the list price of the PSArray(2)
      disposable electrode strip (USD $24.95) was higher than that of the BIS XP sensor
      (USD $17.50), the average sale price (USD $14.95) was identical for both
      electrode systems. Therefore, we conclude that the PSA monitor with the
      PSArray(2) is a cost-effective alternative to the BIS monitor with the XP sensor
      for evaluating consciousness during the induction of and emergence from general
      anesthesia, as well as for titrating propofol and desflurane during the
      maintenance period.

PMID- 15502044
TI  - The efficacy of the arrow staple device for securing central venous catheters to
      human skin.
AB  - We tested the hypothesis that the force necessary to dislodge a central venous
      catheter from human skin is related to its method of attachment. Specifically, we
      compared the peak axial force and torque required to remove a catheter hub
      attached to human skin with 2 3-0 silk sutures, 4 0.022-in. staples, or 4 0.025
      in. staples. We used the tissue from the proximal end of discarded extremities
      after below-knee amputations to serve as a surrogate for the skin of living
      humans that would normally be the site for catheter stabilization. Central venous
      catheter hubs were secured to the area of grossly normal appearing tissue with 2
      3-0 silk sutures or 4 staples. For each attachment method, 16 dislodgement trials
      were conducted. The mean peak force required for axial dislodgement with 3-0 silk
      sutures (40.9 +/- 10.7 N; n = 16) was more than that for 4 0.022-in. staples
      (34.0 +/- 7.2 N; n = 16;P = 0.04) but was not different from that for 4 0.025-in.
      staples (40.4 +/- 5.8 N; n = 16). The major finding of this study is that
      securing a central venous hub with 4 0.025-in. staples is as effective as 2 3-0
      silk sutures in preventing axial dislodgement.

PMID- 15502045
TI  - Electron microscopic evaluations of clot morphology during thrombelastography.
AB  - In this study, we characterized clot morphology with a scanning electron
      microscope (SEM) at time points corresponding to the commonly used
      thrombelastography (TEG) variables, illustrating the correlation of the physical
      clot formation with TEG(R) tracings. The first channel of the TEG analyzer was
      used to obtain the tracings of clot formation, while the sub-samples for the SEM
      were obtained from the second TEG channel. Different types of samples were
      examined, including whole blood, abciximab-treated whole blood, platelet-rich
      plasma (PRP), and abciximab-treated PRP. The SEM images were obtained at reaction
      time, different amplitudes (5-30 mm), maximum amplitude (MA), and at amplitude 60
      min after MA. In the whole blood, coarse fibrin and activated platelets were
      observed at reaction time and fibrin strands progressively became more solid and
      intertwined at amplitude 10 mm and thereafter. Red blood cells were surrounded
      with fibrin strands at amplitude 30 mm and were tightly packed by fibrin strands
      at MA. In abciximab-treated whole blood, red blood cell shape was maintained at
      MA. The process of fibrin formation and platelet activation was also examined in
      PRP. Abciximab did not block platelet shape change, although the blockage of
      fibrin binding to platelets was shown on the TEG analyzer. In summary, we have
      shown structural changes of the forming clot in relation to TEG variables.

PMID- 15502046
TI  - Brand and size matter when choosing a syringe to relieve pressure in a tracheal
      tube cuff.
AB  - We studied the use of an inline syringe as a pressure relief valve for tracheal
      tube cuffs during exposure to nitrous oxide to see if the technique works. Bench
      testing was done to determine the stick and slip characteristics of syringes of
      different brands and sizes. Cuffs were inflated with 20 mL of air, producing a
      cuff pressure of 100-120 mm Hg. Then the plunger of the syringe was allowed to
      passively rebound to a steady pressure at which the plunger stopped ("stick
      pressure"). After several minutes, pressure in the syringe was forcibly increased
      with a second syringe until the plunger started moving again ("slip pressure").
      Stick pressure varied from 18 to 82 mm Hg depending on the brand and size of
      syringe used. Slip pressures exceeded stick pressures by 20-120 mm Hg. Cuff
      pressure increased in a linear fashion during nitrous oxide exposure, and no
      syringe demonstrated automatic pressure reduction. We conclude that a syringe
      attached to the pilot balloon connector can be used to control tracheal tube cuff
      pressure during nitrous oxide anesthesia. However, not all syringes are suitable
      for this purpose: large syringes are better than small syringes, and the Terumo
      brand is more suitable than BD or Monoject. The system does not work
      automatically, and intermittent compression of the syringe plunger to overcome
      static friction is required to avoid overdistension.

PMID- 15502047
TI  - Access denied; care impaired: the benefits of having online medical information
      available at the point-of-care.
AB  - The availability of Internet-enabled computers in the operating room (OR)
      facilitates unparalleled physician access to current peer reviewed research,
      either in abstract or full text format, a development that provides physicians
      with an exciting opportunity to incorporate such findings into clinical practice
      at the point-of-care. In this report I describe how the availability of online
      peer reviewed medical literature altered, in one case a planned surgical
      procedure and, in the other, the interpretation by the anesthesiologist of the
      clinical significance of an intraoperative echocardiographic finding. In case
      one, a free, rather than an intact, internal mammary (IM) artery graft was placed
      to the left anterior descending coronary artery of a patient with renal failure
      and an ipsilateral upper extremity arteriovenous fistula. The change occurred
      after the full text results of a study indicating that steal could well occur
      during the initiation of dialysis if an intact IM was used were made available to
      the surgeon. In case two, the occurrence of mild central mitral regurgitation in
      a Carpentier-Edwards Perimount prosthetic mitral valve was confirmed to be a
      benign finding after a study detailing the long term performance characteristics
      of this valve was accessed online in the OR. The benefits and potential pitfalls
      of searching and interpreting online medical information are discussed.

PMID- 15502048
TI  - Characterization of a new animal model for evaluation of persistent
      postthoracotomy pain.
AB  - Chronic pain after thoracotomy is common, although its basis and therapy have not
      been well characterized. In this study we characterize the allodynic responses
      (mechanical and cold) as well as the histopathologic changes after thoracotomy
      and rib retraction in rats. The antinociceptive effect of systemic and
      intrathecal analgesics was also evaluated. Male Sprague-Dawley rats were
      anesthetized and the right 4th and 5th ribs surgically exposed. The pleura was
      opened between the ribs and a retractor placed under both ribs and opened 8 mm.
      Retraction was maintained for 5, 30, or 60 min. Control animals had pleural
      incision only. Beginning Day 2 postsurgery, animals were tested for mechanical
      allodynia using calibrated von Frey filaments and cold allodynia using acetone
      applied to the incision site. Two weeks after surgery, animals were tested for
      reduction of allodynia with intraperitoneal and intrathecal injections of
      analgesics. Intercostal nerve histology was examined at 14 days postsurgery.
      Allodynia developed in 50% of the animals with 60 min retraction but in only 11%
      and 10% of animals when the retraction time was 5 and 30 min, respectively, and
      in none of the control animals. Allodynic animals showed extensive axon loss in
      the intercostal nerves of the retracted ribs. Allodynia appeared by Day 10 in the
      rib-retraction model and lasted at least 40 days. Systemic morphine sulfate (50%
      effective dose [ED(50)], 1.06 mg/kg) and gabapentin (ED(50), 24.2 mg/kg), as well
      as intrathecal morphine (ED(50), 1.19 nmol), gabapentin (ED(50), 13.8 nmol),
      clonidine (ED(50), 72.7 nmol), and neostigmine (ED(50), 0.54 nmol) reduced
      allodynia. Rib-retraction in rats for 60 min produces allodynia that lasts more
      than 1 mo, and this allodynia is reduced by morphine, gabapentin, clonidine, and
      neostigmine. This new model may be useful for quantifying the efficacy of
      techniques to reduce the frequency and severity of long-term postthoracotomy
      pain.

PMID- 15502049
TI  - The postoperative analgesic effect of tramadol when used as subcutaneous local
      anesthetic.
AB  - Recently, it has been shown that tramadol was an effective local anesthetic in
      minor surgery. In this study, its efficacy for relieving postoperative pain was
      evaluated. Forty patients undergoing minor surgery (lipoma excision and scar
      revision) under local anesthesia were included. The patients were randomly
      allocated into two groups: In group T (n = 20), 2 mg/kg tramadol, and in group L
      (n = 20), 1 mg/kg lidocaine were given subcutaneously. In both groups, the
      injection volume was 5 mL containing 1/200,000 adrenalin. The degree of the
      erythema, burning sensation, and pain at the injection site were recorded.
      Incision response, which is a degree of the pain sensation during incision, was
      recorded and graded with the visual analog scale (VAS) 0-10. After incision, VAS
      values were recorded at 15-min intervals. When the VAS score of the pain during
      surgery exceeded 4, an additional 0.5 mg/kg of the study drug was injected and
      this dosage was added to the total amount. Patients were discharged on the same
      day. Subjects with VAS > or =4 were advised to take paracetamol as needed. No
      side effects were recorded in either group except for 1 patient complaining of
      nausea in group T at the 30th min of operation. After 24 h, patients were called
      and the time of first analgesic use and total analgesic dose taken during the
      postoperative period were recorded. During the 24 postoperative hours, 18 of 20
      (90%) subjects did not need any type of analgesia in group T, whereas this number
      was 10 (50%) in group L (P < 0.05). The time span before taking first analgesic
      medication was longer (4.9 +/- 0.3 h) in group T than that of group L (4.4 +/-
      0.7 h) (P < 0.05). We propose that tramadol can be used as an alternative drug to
      lidocaine for minor surgeries because of its ability to decrease the demand for
      postoperative analgesia.

PMID- 15502050
TI  - Preincisional intravenous pentoxifylline attenuating perioperative cytokine
      response, reducing morphine consumption, and improving recovery of bowel function
      in patients undergoing colorectal cancer surgery.
AB  - Cytokine release during surgery can produce a long-lasting hyperalgesia. Thus,
      preoperatively-administered cytokine inhibitors might reduce the production of
      cytokines, decreasing central nervous system sensitization and improving the
      quality of postoperative pain relief. We investigated the hypothesis that
      preincisional IV pentoxifylline (PTX) treatment could attenuate the release of
      proinflammatory (tumor necrosis factor, interleukin (IL)-1beta, IL-6, and IL-8)
      and antiinflammatory (IL-1 receptor antagonist) cytokines in patients who
      underwent elective colorectal cancer surgery. Forty patients were randomly
      assigned to 1 of 2 groups of 20 each: the PTX group received a PTX 5 mg/kg IV
      infusion before the induction of anesthesia, whereas the control group received
      an equal volume of normal saline. Venous blood samples were obtained at frequent
      intervals. After surgery, all patients received patient-controlled analgesia
      (PCA) morphine for postoperative pain relief. Patients in the PTX group exhibited
      longer PCA trigger times, less morphine consumption, and a faster return of bowel
      function compared with patients in the control group. Moreover, the plasma levels
      of IL-6, IL-8, and IL-1 receptor antagonist were less in the treatment group, and
      there was no significant difference in wound infections, tumor recurrence, or
      metastatic rates between groups during a 2-yr follow-up.

PMID- 15502051
TI  - The efficacy and safety of oral immediate-release oxymorphone for postsurgical
      pain.
AB  - In this double-blind, parallel-group study, we compared 3 oxymorphone immediate
      release (IR) doses with placebo for efficacy and with oxycodone IR and placebo
      for safety in patients with acute moderate-to-severe postsurgical pain. During
      the single-dose phase (n = 300), patients received oxymorphone IR 10, 20, or 30
      mg; oxycodone IR 10 mg; or placebo. All oxymorphone IR doses were superior for
      providing pain relief for 8 h (P < 0.05), with a significant analgesic dose
      response (P < 0.001). Significant pain intensity differences occurred by 45 min
      (20- and 30-mg doses; P < 0.05). Discontinuations for lack of efficacy totaled
      42% among placebo-treated patients and 27% among those treated with oxymorphone
      IR. Patients requiring rescue medication after 3 h were allowed to receive
      additional study drug every 4 to 6 h as needed for the multiple-dose phase (n =
      164). All oxymorphone groups maintained analgesia for 48 h. The median dosing
      interval was >9.5 h for oxymorphone IR 30 mg and > or =7 h for the other groups.
      Opioid-related adverse events, similar among groups, were generally mild or
      moderate. Oxymorphone IR 10, 20, or 30 mg provided significant dose-related pain
      relief compared with placebo, and this relief was maintained over several days
      with a safety profile comparable to that of oxycodone IR.

PMID- 15502052
TI  - Increased systemic catecholamines in complex regional pain syndrome and
      relationship to psychological factors: a pilot study.
AB  - We have demonstrated that subjects with complex regional pain syndrome (CRPS)
      have asymmetric venous pool plasma concentrations of norepinephrine (NE) when
      affected and unaffected limbs are compared, with most demonstrating decreased NE
      levels in the affected limb. This pilot study explored whether systemic venous
      plasma catecholamine levels in CRPS subjects with sympathetically maintained pain
      (SMP) differ from those found in healthy volunteers. We also explored whether
      catecholamine levels were correlated with scores on psychometric measures of
      depression, anxiety, and personality. Venous blood samples from 33 CRPS/SMP
      patients (from unaffected limbs) and 30 healthy control subjects were assayed for
      plasma NE and epinephrine (E) concentrations. Plasma NE levels were significantly
      higher in the CRPS group (P < 0.001). Statistical comparisons of E levels across
      groups did not achieve significance (P < 0.06), although 52% of CRPS/SMP patients
      had E levels exceeding the 95% confidence interval based on control data.
      Significant positive correlations were found between E levels and scores on the
      Beck Depression Inventory and Scales 1, 3, and 6 on the Minnesota Multiphasic
      Personality Inventory-2 (all P < 0.05). This preliminary work suggests that
      increased NE and E levels in CRPS/SMP patients may result from the pain of CRPS,
      consequent affective distress, or both. Alternatively, our findings could reflect
      premorbid adrenergic hyperactivity caused by affective, endocrine, or other
      pathology, which might predispose these individuals to develop the syndrome.
      Definitive studies are needed to examine these hypotheses in detail.

PMID- 15502053
TI  - Publications in anesthesia journals: quality and clinical relevance.
AB  - Clinicians performing evidence-based anesthesia rely on anesthesia journals for
      clinically relevant information. The objective of this study was to analyze the
      proportion of clinically relevant articles in five high impact anesthesia
      journals. We evaluated all articles published in Anesthesiology, Anesthesia &
      Analgesia, British Journal of Anesthesia, Anesthesia, and Acta Anaesthesiologica
      Scandinavica from January to June, 2000. Articles were assessed and classified
      according to type, outcome, and design; 1379 articles consisting of 5468 pages
      were evaluated and categorized. The most common types of article were animal and
      laboratory research (31.2%) and randomized clinical trial (20.4%). A clinically
      relevant article was defined as an article that used a statistically valid method
      and had a clinically relevant end-point. Altogether 18.6% of the pages had as
      their subject matter clinically relevant trials. We compared the Journal Impact
      Factor (a measure of the number of citations per article in a journal) and the
      proportion of clinically relevant pages and found that they were inversely
      proportional to each other.

PMID- 15502054
TI  - Data envelopment analysis to determine by how much hospitals can increase
      elective inpatient surgical workload for each specialty.
AB  - We apply data envelopment analysis to discharge data from the 115 hospitals in
      the rural state of a study hospital to answer three questions. We use a case
      study to investigate the usefulness and limitations of data envelopment analysis
      for assessing three common questions regarding hospital market capture for
      elective inpatient surgery. (i) The hospital studied in this paper performs 40%
      of the neurosurgery and 25% of the inpatient urology surgery in its state.
      Workloads are twice that of the hospitals with the next largest workloads. In
      contrast, the hospital performs 9% of its state's cardiac surgery and has a
      workload half that of the largest volume hospital. The cardiac surgeons want more
      operating room time, faster turnovers, and capital investment for minimally
      invasive equipment. Controlling for the distance patients would need to travel
      for care, would increasing capacity likely increase cardiac surgery workload?
      (ii) The study hospital has fewer hospitalizations for thoracic surgery than for
      any other specialty. Is thoracic surgery inpatient workload of 121 lung
      resections large or small compared with those of orthopedics' 213 hip
      replacements, urology's 132 nephrectomies, and cardiac surgery's 304 coronary
      artery bypass grafts? (iii) The hospital's busiest specialty by discharges is
      orthopedics. How sensitive is the hospital's orthopedic workload to changes in
      decision making at nearby competing hospitals?

PMID- 15502055
TI  - Small-dose capsaicin reduces systemic inflammatory responses in septic rats.
AB  - We investigated the influence of small- and large-dose capsaicin in modulating
      systemic inflammatory responses during different stages of sepsis in rats. Rats
      were divided into six groups: group C, control; group S, sepsis; group CLC, small
      dose of capsaicin (1 mg/kg subcutaneously); group SLC, small dose of capsaicin
      plus sepsis; group CHC, large dose of capsaicin (150 mg/kg subcutaneously); group
      SHC, large dose of capsaicin plus sepsis. Rats were made septic by cecal ligation
      and puncture (CLP). Each group was subdivided into two subgroups. The animals
      were killed at 9 or 18 h after CLP. Plasma concentrations of calcitonin gene
      related peptide (CGRP), tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL
      10, and total nitrite/nitrate (NOx) were measured. Superoxide dismutase and
      malondialdehyde (MDA) were determined in liver, lung, and heart tissues. CGRP was
      increased in groups S, CLC, and SLC when compared with the other groups. In the
      SLC group, plasma concentrations of TNF-alpha, IL-6, NOx, and tissue MDA levels
      were reduced and IL-10 level was increased when compared with groups S and SHC 18
      h after CLP (P < 0.05). Small-dose capsaicin treatment increased antiinflammatory
      IL-10 levels and attenuated the increases in proinflammatory cytokines, NOx, and
      tissue MDA in septic rats.

PMID- 15502056
TI  - Dobutamine inhibits phorbol-myristate-acetate-induced activation of nuclear
      factor-kappaB in human T lymphocytes in vitro.
AB  - Adrenergic drugs are often used for hemodynamic support of cardiac output and
      vasomotor tone in critically ill patients. Recent evidence shows that the
      administration of these vasoactive drugs may affect cytokine release and could
      influence the inflammatory response. However, the mechanism of this
      immunomodulatory effect remains unknown. The nuclear transcription factor-kappaB
      (NF-kappaB) regulates the expression of many cytokines and plays a central role
      in the immune response. Therefore, we examined the effects of various adrenergic
      drugs (dobutamine, xamoterol, clenbuterol, epinephrine, norepinephrine, and
      phenylephrine) on the activation of NF-kappaB, on the NF-kappaB-driven reporter
      gene activity, and on the expression of the NF-kappaB target gene interleukin
      (IL)-8. In addition, we quantified the amount of the NF-kappaB inhibitors
      IkappaBalpha and IL-10. Here we report that dobutamine inhibited the activation
      of NF-kappaB in primary human CD3(+) T lymphocytes. Suppression of NF-kappaB
      involved the stabilization of its inhibitor, IkappaBalpha. The effect appears to
      be beta(2)-receptor specific, because beta(1)-adrenergic and alpha-adrenergic
      substances (i.e., xamoterol, epinephrine, norepinephrine, and phenylephrine) did
      not affect NF-kappaB activation and because dobutamine-mediated inhibition of NF
      kappaB could be prevented by a specific beta(2)-antagonist. Our results
      demonstrate that dobutamine is a potent and specific inhibitor of NF-kappaB, and
      they thus provide a possible molecular mechanism for the immunomodulation
      associated with beta-adrenergic therapy.

PMID- 15502057
TI  - Developing a strategy to improve ventilation in an unprotected airway with a
      modified mouth-to-bag resuscitator in apneic patients.
AB  - The strategies to ensure safety during ventilation of an unprotected airway are
      limiting airway pressure and/or inspiratory flow. In this prospective, randomized
      study we assessed the effect of face mask ventilation with small tidal volumes in
      the modified mouth-to-bag resuscitator (maximal volume, 500 mL) versus a
      pediatric self-inflatable bag versus automatic pressure-controlled ventilation in
      40 adult apneic patients during induction of anesthesia. The mouth-to-bag
      resuscitator requires the rescuer to blow up a balloon inside the self-inflating
      bag that subsequently displaces air which then flows into the patient's airway.
      Respiratory variables were measured with a pulmonary monitor (CP-100). Mouth-to
      bag resuscitator and pressure-controlled ventilation resulted in significantly
      lower (mean +/- sd) peak airway pressure (8 +/- 2 and 8 +/- 1 cm H(2)O), peak
      inspiratory flow rate (0.7 +/- 0.1 and 0.7 +/- 0.1 L/s), and larger inspiratory
      time fraction (33% +/- 5% and 47% +/- 2%) in comparison to pediatric self
      inflating bag ventilation (12 +/- 3 cm H(2)O; 1 +/- 0.2 L/s; 27% +/- 4%; all P <
      0.001). The tidal volumes were similar between groups. No stomach inflation
      occurred in either group. We conclude that using a modified mouth-to-bag
      resuscitator or automatic pressure-controlled ventilation with similar small
      tidal volumes during face mask ventilation resulted in an approximately 25%
      reduction in peak airway pressure when compared with a standard pediatric self
      inflating bag.

PMID- 15502059
TI  - Intrathecal morphine, but not buprenorphine or pentazocine, can induce spastic
      paraparesis after a noninjurious interval of spinal cord ischemia in the rat.
AB  - In this study, we sought to determine the effect of intrathecal (IT) pentazocine
      or buprenorphine on the neurological outcome after a short interval of spinal
      cord ischemia in rats. Although IT morphine (30 microg) induced spastic
      paraparesis after 6 min of aortic occlusion, neither pentazocine (150 microg) nor
      buprenorphine (4 microg) produced neurological dysfunction. Our results indicate
      that the effect of various opioids on the motor function after a noninjurious
      interval of spinal cord ischemia is opioid-specific.

PMID- 15502058
TI  - Intraoperative wake-up test and postoperative emergence in patients undergoing
      spinal surgery: a comparison of intravenous and inhaled anesthetic techniques
      using short-acting anesthetics.
AB  - Surgical procedures on the vertebral column may result in spinal cord damage,
      leading to neurological deficits that demand immediate therapeutical
      intervention. We designed this study to determine which anesthetic regimen allows
      a rapid wake-up test during and after surgery to detect neurological deficits.
      Fifty-four patients were randomly allocated to the following groups: group PR
      (propofol/remifentanil): target-controlled infusion with propofol (plasma
      concentration, 2-4 microg/mL) and remifentanil 0.2-0.5 microg . kg(-1) . min(-1);
      group PS (propofol/sufentanil): propofol (2-4 microg/mL) and repetitive boluses
      of 0.1-0.2 microg/kg of sufentanil adjusted to patients requirements; and group
      DR (desflurane/remifentanil): desflurane/air 3.0-4.0 vol% combined with
      remifentanil 0.2-0.5 microg . kg(-1) . min(-1). Group PS required significantly
      longer times for the onset of breathing (8.9 +/- 1.6 min), elevation of the head
      (17.0 +/- 3.8 min), and motion of the feet (17.0 +/- 7.4 min) than group PR (6.9
      +/- 2.6 min, 9.3 +/- 2.2 min, and 9.4 +/- 2.4 min, respectively) or group DR (5.4
      +/- 0.8 min, 6.1 +/- 1.0 min, and 6.2 +/- 1.0 min, respectively). The anesthetic
      regimen with desflurane and remifentanil allowed faster awakening during and
      after surgery that permitted immediate neurological examination after spinal
      surgery compared with propofol/remifentanil.

PMID- 15502060
TI  - A multicenter randomized controlled trial comparing patient-controlled epidural
      with intravenous analgesia for pain relief in labor.
AB  - In this multicenter, randomized, controlled trial, we sought to determine whether
      patient-controlled epidural analgesia (PCEA) for labor affected the incidence of
      cesarean delivery when compared with patient-controlled IV opioid analgesia
      (PCIA). Healthy, term nulliparous patients in 4 Canadian institutions were
      randomly assigned to receive PCIA with fentanyl (n = 118) or PCEA with 0.08%
      bupivacaine and fentanyl 1.6 microg/mL (n = 124). There was no difference in the
      incidence of cesarean delivery-10.2% (12 of 118) versus 9.7% (12 of 124)-or
      instrumental vaginal delivery-21.2% (25 of 118) versus 29% (36 of 124)-between
      groups. The duration of the second stage of labor was increased in the PCEA group
      by a median of 23 min (P = 0.02). Fifty-one patients (43%) in the PCIA group
      received epidural analgesia: 39 (33%) because of inadequate pain relief and 12
      (10%) to facilitate operative delivery. Patients in the PCIA group required more
      antiemetic therapy (17% versus 6.4%; P = 0.01) and had more sedation (39% versus
      5%; P < 0.001). Maternal mean pain and satisfaction with analgesia scores were
      better in the PCEA group (P < 0.001 and P = 0.02, respectively). More neonates in
      the PCIA group required active resuscitation (52% versus 31%; P = 0.001) and
      naloxone (17% versus 3%; P < 0.001). These observations support the hypothesis
      that PCEA does not result in an increased incidence of obstetrical intervention
      compared with PCIA. PCEA provides superior analgesia and less maternal and
      neonatal sedation compared with PCIA.

PMID- 15502061
TI  - A single injection ultrasound-assisted femoral nerve block provides side effect
      sparing analgesia when compared with intrathecal morphine in patients undergoing
      total knee arthroplasty.
AB  - Postoperative pain after total knee arthroplasty (TKA) is severe, and achieving
      adequate analgesia remains a clinical challenge. We tested the hypothesis that,
      in patients having unilateral TKA under intrathecal (IT) anesthesia, the addition
      of a femoral nerve block would provide superior analgesia when compared with IT
      morphine and demonstrate fewer adverse side effects. In a single-blinded and
      controlled trial, 41 ASA I-III patients undergoing unilateral TKA were randomized
      into 2 groups. Both groups received 15 mg of IT hyperbaric bupivacaine for the
      surgical anesthetic. Group ITM received 250 microg of IT morphine and group FNB
      received an ultrasound-assisted femoral nerve block with 40 mL of 0.5%
      ropivacaine, 5 microg/mL of epinephrine, and 75 microg of clonidine. At 1, 2, 4,
      6, 12, and 24 h postoperatively, we measured visual analog scales for pain,
      cumulative IV morphine consumption, hemodynamics, and side effects. There were no
      statistically significant differences in morphine consumption, pain at rest, or
      pain with movement. However, group FNB had fewer perioperative side effects
      including nausea, vomiting, and pruritus (P < 0.05 for each event). This
      corresponded to a decrease in patient satisfaction in group ITM, in which 20% of
      the patients rated their experience as "unsatisfactory" (P < 0.05). We conclude
      that, in comparison with IT morphine, a single injection femoral nerve block
      provides equivalent analgesia but with a significant reduction in side effects
      for patients having TKA under bupivacaine intrathecal anesthesia.

PMID- 15502062
TI  - Adding a selective obturator nerve block to the parasacral sciatic nerve block:
      an evaluation.
AB  - Our aim was to objectively evaluate the efficacy of obturator nerve anesthesia
      after a parasacral block. Patients scheduled for knee surgery had a baseline
      adductor strength evaluation. After a parasacral block with 30 mL 0.75%
      ropivacaine, sensory deficit in the sciatic distribution (temperature
      discrimination) and adductor strength were assessed at 5-min intervals. Patients
      with an incomplete sensory block (defined as a temperature discrimination score
      of less than 2 in the 3 cutaneous distributions of the sciatic nerve tested) 30
      min after the parasacral block were excluded from the study. Subsequently, a
      selective obturator block was performed with 7 mL 0.75% ropivacaine and adductor
      strength was reassessed at 5 min intervals for 15 min. Finally, a femoral block
      was performed using 10 mL 0.75% ropivacaine. Patient discomfort level during each
      block was assessed using a visual analog scale (VAS). Thirty-one patients
      completed the study. Five patients were excluded as a result of inadequate
      sensory block in the sciatic distribution 30 min after the parasacral block
      (success rate of 89%). Thirty min after the parasacral block, adductor strength
      decreased by 11.3% +/- 7% compared with baseline (85 +/- 24 versus 97 +/- 28 mm
      Hg, P = 0.002). Fifteen min after the obturator nerve block, adductor muscle
      strength decreased by an additional 69% +/- 7% (16.6 +/- 15 versus 85 +/- 24 mm
      Hg, P < 0.0001). VAS scores were similar for all blocks (26 +/- 19, 28 +/- 24,
      and 27 +/- 19 mm for parasacral, obturator, and femoral respectively). Four
      parasacral blocks were simulated in 2 fresh cadavers using 30 mL of colored latex
      solution. The spread of the die in relation to the obturator nerve was assessed.
      Injection of 30 mL colored latex into cadavers resulted in spread of the
      injectate restricted to the sacral plexus. These findings demonstrate the
      unreliability of parasacral block to achieve anesthesia of the obturator nerve. A
      selective obturator block should be considered in the clinical setting when this
      is desirable.

PMID- 15502063
TI  - Successful removal of a knotted fascia iliaca catheter: principles of patient
      positioning for peripheral nerve catheter extraction.
AB  - Peripheral nerve catheters are typically advanced a substantial distance into a
      perineural sheath, theoretically increasing the risk of catheter knotting and
      kinking. In this case report, we describe successful removal of a knotted fascia
      iliaca catheter and discuss principles of nonsurgical catheter extraction. A 64
      yr-old woman with bilateral coxarthrosis presented for total hip arthroplasty
      under combined general/regional anesthesia. A 20-gauge fascia iliaca catheter was
      inserted before surgery by using a loss-of-resistance "double pop" technique. The
      catheter was uneventfully advanced 10 cm past the needle tip. After injection of
      30 mL of 0.5% bupivacaine with 1:200,000 epinephrine and 100 microg of clonidine,
      general anesthesia was induced. An infusion of 0.1% bupivacaine at 20 mL/h was
      initiated in the recovery room for postoperative analgesia. Approximately 48 h
      later, resistance was encountered during catheter removal. Catheter extraction
      was attempted by altering patient positioning, including the supine position
      during which the catheter placement had occurred. Successful catheter removal was
      achieved by decreasing tension on the fascia lata and fascia iliaca through
      flexion of the hip joint and by applying firm, steady traction. The catheter was
      removed intact with a knot approximately 2 cm from the distal tip. We conclude
      that the principles for removal of entrapped peripheral catheters are not well
      known and may differ from those for neuraxial catheters. Patient positioning to
      minimize pressure and tension on the perineural soft tissues may facilitate
      catheter removal.

PMID- 15502064
TI  - A proposed classification and scoring system for supraglottic sealing airways: a
      brief review.
AB  - We provide an approach to evaluating sealing supraglottic airways by using a
      classification based on a sealing mechanism. Three main sealing mechanisms are
      identified, thus defining three groups: cuffed perilaryngeal sealers, cuffed
      pharyngeal sealers, and uncuffed anatomically preshaped sealers. We provide a
      brief overview of supraglottic airways and present a scoring system that is
      relevant to particular requirements. Scoring airways for routine applications is
      the example provided.

PMID- 15502065
TI  - The laryngeal mask airway Unique versus the Soft Seal laryngeal mask: a
      randomized, crossover study in paralyzed, anesthetized patients.
AB  - We tested the hypothesis that ease of insertion, oropharyngeal leak pressure,
      fiberoptic position, ease of ventilation, and mucosal trauma are different for
      the Soft Seal laryngeal mask airway (SSLM) and the laryngeal mask airway Unique
      (LMA-U). Ninety paralyzed, anesthetized adult patients (ASA I-II; 18-80 yr old)
      were studied. Both devices were inserted into each patient in random order.
      Oropharyngeal leak pressure and fiberoptic position were determined during cuff
      inflation from 0-40 mL in 10-mL increments and at an intracuff pressure of 60 cm
      H(2)O. Ease of ventilation was determined by controlling ventilation for 10 min
      at 8 and 12-mL/kg tidal volume and recording hemoglobin oxygen saturation, end
      tidal CO(2), leak fraction, peak airway pressure, and the presence or absence of
      gastric insufflation. Mucosal trauma was determined by examining the first
      randomized device for the presence of visible and occult blood. Insertion time
      was shorter (P = 0.0001) and fewer attempts were required (P = 0.005) for the LMA
      U. There were no failed uses of either device. Oropharyngeal leak pressures were
      similar, but fiberoptic position was superior with the LMA-U (P < or = 0.0003).
      There were no differences in hemoglobin oxygen saturation, end-tidal CO(2), leak
      fraction, or peak airway pressure at either tidal volume. Gastric insufflation
      was not detected in either group at either tidal volume. The frequency of visible
      (P = 0.009) and occult blood (P = 0.0001) was less with the LMA-U. We conclude
      that the LMA-U is superior to the SSLM in terms of ease of insertion, fiberoptic
      position, and mucosal trauma, but similar in terms of oropharyngeal leak pressure
      and ease of ventilation.

PMID- 15502066
TI  - Decreased factor XIII availability for thrombin and early loss of clot firmness
      in patients with unexplained intraoperative bleeding.
AB  - To explore relevant changes in unexplained intraoperative bleeding, we evaluated
      elements of the final steps of the coagulation cascade in 226 consecutive
      patients undergoing elective surgery. Patients were stratified for the occurrence
      of unexplained intraoperative bleeding according to predefined criteria. Twenty
      patients (8.8%) developed unexplained bleeding. The median intraoperative blood
      loss was 1350 mL (bleeders) and 400 mL (nonbleeders) (P < 0.001). Fibrinogen and
      Factor XIII (F. XIII) were more rapidly consumed in bleeders (P < 0.001). Soluble
      fibrin formation (fibrin monomer) was increased in bleeders throughout surgery (P
      < or = 0.014). However, F. XIII availability per unit thrombin generated was
      significantly decreased in bleeders before, during, and after surgery (P < or =
      0.051). Computerized thrombelastography showed a parallel, significant reduction
      in clot firmness. We suggest that mild preexisting coagulopathy is not rare in
      surgical patients and probably can result in clinically relevant intraoperative
      bleeding. This hemostatic disorder shows impaired clot firmness, probably
      secondary to decreased cross-linking (due to a loss of F. XIII, both in absolute
      measures and per unit thrombin generated). We suggest that the application of F.
      XIII might be worthwhile to test in a prospective clinical trial to increase clot
      firmness in patients at risk for this intraoperative coagulopathy.

PMID- 15502067
TI  - Polypoid hyperplasia of the larynx misdiagnosed as a malpositioned laryngeal mask
      airway.
AB  - Polypoid hyperplasia of the vocal cords, associated with smoking, reflux, and
      vocal cord abuse, results in inflammation and edema. This condition can produce
      partial airway obstruction during positive pressure ventilation.

PMID- 15502068
TI  - Prolonged postoperative disorientation after methylene blue infusion during
      parathyroidectomy.
AB  - Methylene blue 7.5 mg/kg is frequently given at our institution during
      parathyroidectomy. The dye preferentially stains the parathyroids so as to
      provide better surgical visualization. Other than causing a pseudocyanosis, the
      technique is generally considered to be rather innocuous. We report a case of a
      patient who, after this procedure, had a postoperative course that was unusual
      because of slowly resolving altered mental status.

PMID- 15502069
TI  - Dopamine and radial artery: implications for clinical practice.

PMID- 15502070
TI  - Incidental radiologic discovery of a large posterior pharyngeal mass in a
      tracheally intubated child with facial anomalies.

PMID- 15502071
TI  - Are preemptive analgesic effects of ketamine linked to inadequate perioperative
      analgesia?

PMID- 15502072
TI  - Awake intubation is indicated in pregnant women with difficult airways.

PMID- 15502073
TI  - Fluid leak from epidural puncture site: a diagnostic dilemma.

PMID- 15502074
TI  - Study regarding anesthesia outcomes cites outdated studies.

PMID- 15502075
TI  - Usefulness of sweat testing for the detection of cannabis smoke.

PMID- 15502076
TI  - Multiplex assays with fluorescent microbead readout: a powerful tool for mutation
      detection.

PMID- 15502077
TI  - Noninvasive lithium monitoring.

PMID- 15502078
TI  - Evaluating interference caused by lipemia.

PMID- 15502079
TI  - DNA bacteriophage as controls for clinical viral testing.

PMID- 15502080
TI  - Development of an ELISA for the determination of the major haptoglobin phenotype:
      an interesting technical development and its potential consequences.

PMID- 15502081
TI  - In silico prediction of the deleterious effect of a mutation: proceed with
      caution in clinical genetics.
AB  - When a sequence variation is found in a candidate gene for a disease, it is
      important to establish whether this change is neutral or responsible for the
      observed disorders in a patient. To answer this question, in the absence of
      further experimental investigations, several simulation programs have been
      proposed to predict whether a nonsynonymous single-nucleotide polymorphism is
      likely to have or not have a deleterious effect on the phenotype. In this work,
      we tested two such programs, PolyPhen and SIFT, using two kinds of targets. The
      first ones concerned the products of the hemoglobin and glucose-6-phosphate
      dehydrogenase genes, which are abundantly documented. The second concerned two
      systems for which much less information is available: (a) the TNFRSF1A gene,
      implicated in tumor necrosis factor receptor-associated periodic syndrome, and
      (b) the MEFV gene, which is believed to be involved in familial Mediterranean
      fever. Our data suggest that, from a practical point of view, these programs
      should not be used to decide, in the absence of other tests or arguments, whether
      the sequence variation found in a patient is or is not responsible for the
      disease. The consequence of an erroneous prediction may be disastrous in the
      perspective of genetic counseling.

PMID- 15502083
TI  - ELISA for determination of the haptoglobin phenotype.

PMID- 15502082
TI  - Validation of a new automated renin assay.
AB  - BACKGROUND: Measurement of plasma renin is important for the treatment of
      patients with congenital adrenal hyperplasia (CAH) and in the evaluation of
      patients with suspected hyperaldosteronism. Immunologic assays for plasma renin
      offer easier implementation and standardization than enzyme-kinetic assays for
      plasma renin activity, but their sensitivity and specificity have been
      questioned. We studied a renin immunochemiluminescence assay on an automated
      platform. METHODS: Renin was measured by an enzymatic assay, by IRMA, and by the
      new Nichols Advantage Specialty System immunochemiluminometric assay (ICMA), in
      plasmas from unselected individuals from our outpatient departments and in
      samples from patients with selected diagnoses. RESULTS: The detection limit in
      the ICMA was 0.1 mU/L. The recovery was >90%, and the imprecision (CV) was
      generally <9%. Mean (SD) concentrations measured by ICMA were 32 (21)% lower than
      those measured by IRMA. Renin concentrations as measured by ICMA were identical
      in serum and EDTA-, heparin-, and citrate-anticoagulated plasmas. Prolonged
      incubation of whole blood at room temperature before centrifugation did not
      affect renin concentrations. The central 95% interval for 80 healthy adults was 6
      85.5 mU/L. Plasma renin as assessed by ICMA in patients with primary
      hyperaldosteronism was <0.2 mU/L. CONCLUSIONS: The performance characteristics of
      the new renin ICMA allow its use for patients with CAH and for the diagnosis of
      mineralocorticoid hypertension. In view of the variability of renin
      concentrations, use for other forms of hypertension or physiologic research calls
      for the development of uniform sampling protocols.

PMID- 15502084
TI  - Effect of specimen collection on routine coagulation assays and D-dimer
      measurement.

PMID- 15502085
TI  - Concentration of circulating rhodopsin mRNA in diabetic retinopathy.

PMID- 15502086
TI  - Multimutational analysis of eleven cystic fibrosis mutations common in the
      Mediterranean areas.

PMID- 15502087
TI  - Rapid and simple tandem mass spectrometry method for determination of serum
      cotinine concentration.

PMID- 15502088
TI  - Factors influencing isoprotein dependency of polyclonal apolipoprotein(a) assays.

PMID- 15502089
TI  - Simultaneous measurement of kynurenine and tryptophan in human plasma and
      supernatants of cultured human cells by HPLC with coulometric detection.

PMID- 15502090
TI  - ROC analysis comparison of three assays for the detection of antibodies against
      double-stranded DNA in serum for the diagnosis of systemic lupus erythematosus.

PMID- 15502091
TI  - Analysis of methylated genes in peritoneal fluids of ovarian cancer patients: a
      new prognostic tool.

PMID- 15502092
TI  - Procollagen type I amino-terminal propeptide: pediatric reference data and
      relationship with procollagen type I carboxyl-terminal propeptide.

PMID- 15502093
TI  - High-throughput liquid chromatography-tandem mass spectrometry assay for plasma
      theophylline and its metabolites.

PMID- 15502094
TI  - Detection of epigenetic changes in fecal DNA as a molecular screening test for
      colorectal cancer: a feasibility study.

PMID- 15502095
TI  - Rapid detection of ITPA 94C>A and IVS2 + 21A>C gene mutations by real-time
      fluorescence PCR and in vitro demonstration of effect of ITPA IVS2 + 21A>C
      polymorphism on splicing efficiency.

PMID- 15502096
TI  - Variability of serum soluble intercellular adhesion molecule-1 measurements
      attributable to a common polymorphism.

PMID- 15502097
TI  - Detection of fetal DNA and RNA in placenta-derived syncytiotrophoblast
      microparticles generated in vitro.

PMID- 15502098
TI  - High ischemia-modified albumin concentration reflects oxidative stress but not
      myocardial involvement in systemic sclerosis.

PMID- 15502099
TI  - Evaluation of imprecision for analysis of short tandem repeats by use of mixed
      blood cells in variable concentrations.

PMID- 15502100
TI  - Locked nucleic acid-enhanced detection of 1100delC*CHEK2 germ-line mutation in
      Spanish patients with hematologic malignancies.

PMID- 15502101
TI  - Cardiac biomarkers for detection of myocardial infarction: perspectives from past
      to present.
AB  - With great pleasure and anticipation in recognition of Clinical Chemistry's 50th
      anniversary, I have been able to arm-twist four talented scientists to document
      their impressive marks on the science of diagnostics in the field of cardiac
      biomarkers and detection of myocardial infarction. Their exciting discoveries and
      applications have dramatically influenced the fields of laboratory medicine and
      cardiology and have greatly influenced the care and management of thousands of
      patients suffering from coronary artery disease leading to acute myocardial
      infarction. As a matter of historical record, I owe a great deal of thanks to
      each one of the coauthors of this special report because each one has personally
      influenced my scientific career. I met Dr. Rosalki, during my postdoctoral
      training, at a national AACC meeting, where he kindly answered my numerous
      queries regarding creatine kinase enzymology and muscle physiology. Dr. Roberts,
      while serving as Director of the Coronary Care Unit at Washington University in
      St. Louis, generously allowed this fledgling fellow into his laboratory and
      shared many of his clinical and experimental findings with me. Dr. Katus, whom I
      first met at a scientific meeting sponsored by Boehringer Mannheim in 1986 in
      Bavaria, where I first became fascinated with cardiac troponin T, has remained a
      friend and colleague. Lastly, Dr. Ladenson, who as mentor, scientific colleague,
      and close friend remains ultimately responsible for both my professional growth
      as a clinical chemist (he was my postdoctoral fellowship advisor) and for
      stimulating and encouraging my goals and aspirations in the field of cardiac
      biomarkers. With the descriptions of the ground-breaking science described below,
      I am extremely excited and optimistic that the future of cardiac biomarkers is
      secure and open to new discoveries by the Rosalkis, Robertses, Katuses, and
      Ladensons of the future.

PMID- 15502102
TI  - Hyperlipidemia in patients with apolipoprotein E 2/2 phenotype: apolipoprotein A5
      S19W mutation as a cofactor.

PMID- 15502103
TI  - Spurious tumor necrosis factor-alpha and interleukin-6 production by human
      monocytes from blood collected in endotoxin-contaminated vacutainer blood
      collection tubes.

PMID- 15502104
TI  - Interpreting method comparison studies by use of the bland-altman plot:
      reflecting the importance of sample size by incorporating confidence limits and
      predefined error limits in the graphic.

PMID- 15502105
TI  - No interference by diclofenac with the new Vitros FT3II assay reagent.

PMID- 15502106
TI  - Extraction/chromatographic testosterone RIA can be used as the "gold standard"
      for determining the reliability of direct testosterone immunoassay measurements.

PMID- 15502109
TI  - CXCL11 attenuates bleomycin-induced pulmonary fibrosis via inhibition of vascular
      remodeling.
AB  - Aberrant vascular remodeling is a central hallmark for the development and
      progression of idiopathic pulmonary fibrosis. The mechanisms underlying the
      pathophysiologic alterations, however, are poorly understood. A recent phase II
      trial of interferon gamma-1b has demonstrated a trend toward a decrease in
      profibrotic and proangiogenic biologic markers, and upregulation of lung CXCL11
      mRNA and bronchoalveolar lavage fluid and plasma protein levels of CXCL11. We
      hypothesized that net aberrant vascular remodeling seen during the pathogenesis
      of fibroplasia and deposition of extracellular matrix during bleomycin-induced
      pulmonary fibrosis can be attenuated by treatment with the angiostatic ELR(-) CXC
      chemokine, CXCL11. In a preclinical model, systemic administration of CXCL11
      reduced pulmonary collagen deposition, procollagen gene expression, and
      histopathologic fibroplasia and extracellular matrix deposition in the lung of
      bleomycin-treated mice. CXCL11 treatment significantly reduced bleomycin-induced
      pulmonary fibrosis without altering specific lung leukocyte populations. CXCR3 is
      not expressed on fibroblasts and CXCL11 had no direct functional effect on
      pulmonary fibroblasts. The angiogenic activity in the lung was significantly
      decreased, however, and CXCL11 treatment reduced the total number of endothelial
      cells in the lung following bleomycin exposure. The results suggest that CXCL11
      inhibits pulmonary fibrosis by altering aberrant vascular remodeling.

PMID- 15502110
TI  - beta1-Integrins mediate enhancement of airway smooth muscle proliferation by
      collagen and fibronectin.
AB  - Airway smooth muscle (ASM) accumulation and enrichment of the extracellular
      matrix (ECM) with type I collagen and fibronectin are major pathologic features
      of airway remodeling in asthma. These ECM components confer enhanced ASM
      proliferation in vitro, but a requirement for specific integrin ECM receptors has
      not been examined. Here, we examined the mitogen platelet-derived growth factor
      (PDGF)-BB on beta1-integrin expression on human ASM cells cultured on these ECM
      substrates and defined the involvement of specific integrins in cell attachment
      and proliferation using integrin-neutralizing antibodies. PDGF-BB-dependent
      proliferation was enhanced two- to threefold by monomeric type I collagen or
      fibronectin and to a lesser extent by vitronectin; other interstitial ECM
      components (fibrillar type I and III collagen and tenascin-C) had no effect.
      Except for increased alpha3 expression induced by PDGF-BB and monomeric type I
      collagen or fibronectin, alpha1, alpha2, alpha4, alpha5, alphav, and alphavbeta3
      integrins were unchanged compared with unstimulated cells on plastic. Blocking
      antibodies revealed alpha2beta1- and alphavbeta3-mediated attachment to monomeric
      type I collagen, whereas attachment to fibronectin required alpha5beta1. In
      contrast, enhancement of PDGF-BB-dependent proliferation by either monomeric type
      I collagen or fibronectin required alpha2beta1, alpha4beta1, and alpha5beta1
      integrins. These data suggest multiple beta1-integrins regulate enhanced ASM
      proliferative responses.

PMID- 15502111
TI  - Increased interleukin-4, interleukin-5, and interferon-gamma in airway CD4+ and
      CD8+ T cells in atopic asthma.
AB  - Increased Th2 cytokine production in asthma is widely accepted, but excess
      production by asthmatic human airway CD4(+) T cells has not been demonstrated,
      nor has a relationship with disease severity. The importance of airway CD8(+) T
      cell type 1 and type 2 cytokine production in asthma is unknown. We investigated
      frequencies of IFN-gamma, interleukin (IL)-4 and IL-5 producing CD4(+) and CD8(+)
      blood and sputum T cells from normal subjects and subjects with asthma and
      compared between cell subsets, subject groups, and body compartments with and
      without in vitro stimulation and investigated relationships between cytokine
      production and asthma severity. Production of IL-4, IL-5, and IFN-gamma by
      unstimulated sputum CD4(+) and CD8(+) T cells was increased in subjects with
      asthma and related to disease severity, more for CD8(+) than for CD4(+) T cells.
      Frequencies of sputum CD8(+) T cells producing type 1 and type 2 cytokines were
      similar to those of CD4(+) T cells. In vitro stimulation polarized peripheral
      blood cytokine production toward IFN-gamma production, significantly more in
      subjects with asthma than in normal subjects. These data demonstrate increased
      type 1 and 2 cytokine production in CD4(+) and CD8(+) T cells in sputum and
      relate production to disease severity. Findings in blood did not reflect those in
      airways.

PMID- 15502112
TI  - Budesonide/formoterol combination therapy as both maintenance and reliever
      medication in asthma.
AB  - Asthma control is improved by combining inhaled corticosteroids with long-acting
      beta2-agonists. However, fluctuating asthma control still occurs. We hypothesized
      that in patients receiving low maintenance dose budesonide/formoterol (bud/form),
      replacing short-acting beta2-agonist (SABA) reliever with as-needed bud/form
      would provide rapid symptom relief and simultaneous adjustment in
      antiinflammatory therapy, thereby reducing exacerbations. In this double-blind,
      randomized, parallel-group study, 2,760 patients with asthma aged 4-80 years
      (FEV1 60-100% predicted) received either terbutaline 0.4 mg as SABA with bud/form
      80/4.5 microg twice a day (bud/form + SABA) or bud 320 microg twice a day (bud +
      SABA) or bud/form 80/4.5 microg twice a day with 80/4.5 microg as-needed
      (bud/form maintenance + relief). Children used a once-nocte maintenance dose.
      Bud/form maintenance + relief prolonged time to first severe exacerbation (p <
      0.001; primary endpoint), resulting in a 45-47% lower exacerbation risk versus
      bud/form + SABA (hazard ratio, 0.55; 95% confidence interval, 0.44, 0.67) or bud
      + SABA (hazard ratio, 0.53; 95% confidence interval 0.43, 0.65). Bud/form
      maintenance + relief also prolonged the time to the first, second, and third
      exacerbation requiring medical intervention (p < 0.001), reduced severe
      exacerbation rate, and improved symptoms, awakenings, and lung function compared
      with both fixed dosing regimens.

PMID- 15502113
TI  - Surfactant and physiologic responses of preterm lambs to continuous positive
      airway pressure.
AB  - Although continuous positive airway pressure (CPAP) is used frequently for
      preterm infants, the relationships between the amount of surfactant and lung
      physiologic and injury responses to CPAP are unknown. Therefore, saturated
      phosphatidylcholine (Sat PC) was measured to quantify the surfactant necessary
      for preterm lambs to breathe successfully on a CPAP of 5 cm H(2)O (CPAP 5). Five
      of 21 lambs delivered at 130-136 days gestation failed to keep PCO(2) below 100
      mm Hg by 2 hours. The lambs that failed had less than 1.9 micromol/kg Sat PC in
      bronchoalveolar fluid (approximately 3% the pool size at term), less surfactant
      secretion, and less large aggregate surfactant. Physiologic responses of other
      132-day preterm lambs after 2 or 6 hours of CPAP 5, 8 cm H(2)O CPAP (CPAP 8), or
      mechanical ventilation were then characterized. At 6 hours, oxygenation and lung
      gas volumes were higher with CPAP 8 relative to the other groups and VE was
      decreased with CPAP 8 relative to CPAP 5. Lung dry/wet ratios were greater for
      the CPAP groups than for the mechanical ventilation group. A small amount of
      endogenous Sat PC is required for preterm lambs to breathe successfully with
      CPAP. CPAP 8 improves early newborn respiratory transition relative to CPAP 5.

PMID- 15502114
TI  - Parental smoking and airway reactivity in healthy infants.
AB  - Parental tobacco smoking is associated with lower airway function and an
      increased incidence of wheezy respiratory illnesses in infants. We evaluated in
      76 healthy infants whether exposure to parental tobacco smoking was associated
      with airway hyperreactivity, which could contribute to lower airway function and
      the increased wheezy illnesses. Airway function was measured using the raised
      volume rapid thoracic compression technique, and airway reactivity was assessed
      by methacholine challenge (0.015-10 mg/ml), which was stopped for a more than 30%
      decrease in forced expiratory flow (FEF)(75) or the final dose with a less than
      30% decrease. Parental tobacco smoking was associated with lower baseline airway
      function (FEF(50), 600 vs. 676 ml/second, p < 0.04; FEF(25-75), 531 vs. 597
      ml/second, p < 0.05). Infants exposed to tobacco smoking were approximately half
      as likely to develop a more than 30% decline in FEF(75) at any given methacholine
      dose (hazard ratio = 0.4, p = 0.001). In addition, a history of asthma in an
      extended family member increased the likelihood that an infant would develop a
      more than 30% decline in FEF(75) (hazard ratio = 1.7, p = 0.04). We conclude that
      exposure to parental smoking is associated with lower airway function but not
      increased airway reactivity; however, family history of asthma is associated with
      heightened airway reactivity.

PMID- 15502115
TI  - Wheeze phenotypes and lung function in preschool children.
AB  - Distinct phenotypes can be identified in childhood wheezing illness. Within the
      context of a birth cohort study, we investigated the association between
      preschool lung function and phenotypes of wheeze. From parentally reported
      history of wheeze (interviewer-administered questionnaire, age 3 and 5 years),
      children were classified as never wheezers, transient early wheezers, late-onset
      wheezers, or persistent wheezers. Lung function (specific airway resistance
      [sRaw]; kPa/second) was assessed at age 3 (n = 463) and 5 years (n = 690).
      Persistent wheezers had markedly poorer lung function compared with other groups.
      In children who had wheezed by age 3, the risk of persistent wheeze increased
      with increased sRaw (odds ratio [OR] 5.2, 95% confidence interval [CI] 1.3-22.0;
      p = 0.02). In a multivariate model, increasing sRaw (OR 5.5, 95% CI 1.2-25.9; p =
      0.03) and the child's sensitization (OR 2.8, 95% CI 1.3-5.8; p = 0.008) were
      significant independent predictors of persistent wheezing. We found no
      association between lung function at age 3 and late-onset wheeze in children who
      had not wheezed previously (OR 0.6, 95% CI 0.07-5.3; p = 0.64). In conclusion,
      poor lung function at age 3 predicted the subsequent persistence of symptoms in
      children who had wheezed within the first 3 years, but was not associated with
      the onset of wheeze after age 3 in children who had not wheezed previously.

PMID- 15502116
TI  - One-year outcome after severe pulmonary exacerbation in adults with cystic
      fibrosis.
AB  - We retrospectively studied the outcomes of adult patients with cystic fibrosis
      (CF) hospitalized for severe pulmonary exacerbations (69 cases) between January
      1997 and June 2001. Cases were treated either in the Pulmonary Department (n =
      46) or in the intensive care unit (ICU) (n = 23) depending on severity.
      Noninvasive mechanical ventilation was used in 61% (14 of 23) and 33% (15 of 46)
      of cases treated in the ICU and the Pulmonary Department groups, respectively.
      Invasive ventilation was necessary in 4 of 23 cases treated in the ICU. The 1
      year survival rate was 52% (12 of 23) and 91% (42 of 46) in the ICU and the
      Pulmonary Department groups, respectively. Lung transplantation was performed in
      two patients from the ICU group and in five patients from the Pulmonary
      Department group after hospital discharge. Factors predictive of death were prior
      colonization with Burkholderia cepacia and rapid decline in FEV1 before admission
      and severity of exacerbations (severity of hypoxemia and hypercapnia, simplified
      acute physiology score II and logistic organ dysfunction (LOD) scores,
      requirement of noninvasive mechanical ventilation, and hospitalization in the
      ICU) in the univariate analysis and were prior colonization with B. cepacia, the
      severity of hypoxemia at admission, and hospitalization in the ICU in the
      multivariate analysis. In 1-year survivors, pulmonary exacerbation did not affect
      the progression of the disease.

PMID- 15502117
TI  - Endoscopic ultrasound in non-small cell lung cancer and negative mediastinum on
      computed tomography.
AB  - Despite technical advances in staging non-small cell lung cancer (NSCLC),
      accurate staging remains a challenge. Endoscopic ultrasound is useful in staging
      NSCLC when lymphadenopathy is present on a computed tomography (CT), but its role
      in the absence of lymphadenopathy on CT has not been well defined. Therefore, we
      sought to determine the clinical impact of endoscopic ultrasound (EUS) in staging
      NSCLC in absence of mediastinal lymphadenopathy on CT. Seventy-six patients with
      NSCLC with absence of mediastinal lymphadenopathy on CT were enrolled and
      followed prospectively. EUS-guided fine-needle aspiration was performed on sites
      that were suspicious for metastases. Surgical pathology after thoracotomy was
      used as the reference standard for assessing accuracy. Sixty-two (86%) patients
      underwent surgery, and 10 (13%) did not. EUS precluded surgery in 9 patients
      (12%) and influenced management in 18 (25%) of all patients in this study. EUS
      detected malignant mediastinal lymphadenopathy more frequently in patients with
      lower lobe and hilar cancers combined compared with upper lobe cancers (p =
      0.004). EUS played a significant role in identifying patients with unresectable
      (N3) NSCLC when adenopathy was not present on CT imaging and appears to be more
      sensitive in detecting lymph node metastases in lower lobe and hilar NSCLC
      compared with upper lobe NSCLC.

PMID- 15502118
TI  - Direct puncture embolization for paragangliomas: promising results but
      preliminary data.

PMID- 15502119
TI  - Is a large hat size hazardous to your health?

PMID- 15502120
TI  - 3T MR imaging: the pros and cons.

PMID- 15502121
TI  - Intratumoral injection of cyanoacrylate glue in head and neck paragangliomas.
AB  - BACKGROUND AND PURPOSE: Substantial intraoperative bleeding during surgical
      removal of head and neck paragangliomas may be a major problem in the management
      of these highly vascularized tumors. Traditional preoperative embolization via a
      transarterial approach has proved beneficial but is often limited by complex
      vascular anatomy and unfavorable locations. We report our experience with the
      preoperative devascularization of head and neck paragangliomas by using direct
      puncture and an intralesional injection of cyanoacrylate. METHODS: We
      retrospectively analyzed nine consecutive patients with head and neck
      paragangliomas who were referred for preoperative devascularization. Three
      patients were treated for carotid-body tumors; two for vagal lesions; and four,
      for jugular paragangliomas. Direct puncture of the lesion was performed by using
      roadmap fluoroscopic guidance. Acrylic glue was injected by using continuous
      biplane fluoroscopy. All patients underwent postembolization control angiography
      and immediate postoperative CT scanning. RESULTS: Angiograms showed that complete
      devascularization was achieved in all cervical glomus tumors, whereas subtotal
      devascularization was achieved in jugular paragangliomas. In this latter
      location, the injection of acrylic glue was limited by the potential risk of
      reflux into normal brain territory via feeders from the internal carotid or
      vertebral artery. The tumors were surgically removed and histologically examined.
      No technical or clinical complications related to the embolization procedure
      occurred. CONCLUSION: Percutaneous puncture of paragangliomas in the head and
      neck region and their preoperative devascularization by intralesional injection
      of acrylic glue is a feasible, safe, and effective technique.

PMID- 15502122
TI  - Postoperative 3D angiography in intracranial aneurysms.
AB  - BACKGROUND AND PURPOSE: Postsurgical evaluation of patients with intracranial
      aneurysms is important because there is a risk of regrowth and subarachnoid
      hemorrhage from residual aneurysms. We assessed the role and value of 3D
      angiography in this evaluation. METHODS: Images from both 3D angiography and
      digital subtraction angiography (DSA) were preoperatively obtained in 71
      consecutive patients with 88 intracranial clipped aneurysms. We analyzed the
      incidence of postoperative residual aneurysms and compared the 3D angiographic
      and DSA images in these patients. RESULTS: With 3D angiography, 37 residual
      aneurysms were found among 88 clipped aneurysms. These comprised 12 large
      residual necks and 25 small, dog-eared remnants. DSA demonstrated 12 large,
      residual necks and only six small, dog-eared remnants. 3D angiography also
      demonstrated the clips, aneurysms, and parent arteries simultaneously, enabling
      us to appreciate the clip-aneurysm configuration completely. CONCLUSION: 3D
      angiography allowed us to detect more residual aneurysms after surgical clip
      placement than did conventional DSA, although none of those detected on only 3D
      angiography were judged to require additional treatment. 3D angiography may
      provide baseline data for the long-term follow-up of postsurgical aneurysms.

PMID- 15502123
TI  - Sequential combination of intravenous recombinant tissue plasminogen activator
      and intra-arterial urokinase in acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Combined intravenous (IV) and intra-arterial (IA)
      thrombolytic therapy may be faster and easier to initiate than monotherapy, and
      its recanalization rate may be better as well. The sequential combination of
      recombinant tissue plasminogen activator (rTPA) and urokinase (UK) has
      synergistic and complementary effects on clot lysis. We prospectively evaluated
      the effectiveness and safety of sequential combination of IV rTPA and IA UK in
      acute ischemic stroke. METHODS: IV rTPA was administered to patients with acute
      stroke within 3 hours of onset. Those whose condition had not improved at the end
      of rTPA infusion were further treated with selective IA UK. We evaluated baseline
      and 30-day National Institutes of Health Stroke Scale (NIHSS) scores and 90-day
      modified Rankin Scale scores. RESULTS: Thirty patients were initially treated
      with IV rTPA; 24 were further treated with IA UK. Four patients who had rapid
      reocclusion following initial successful IA therapy received IV abciximab.
      Fourteen of 24 patients who underwent angiography had an effective perfusion
      state of Thrombolysis in Myocardial Infarction grade 3 flow. Median baseline and
      30-day NIHSS scores were 18 and 2, respectively. Eighteen patients improved to a
      modified Rankin scale score of 0 or 1 after 90 days. Symptomatic hemorrhage
      developed in two patients. CONCLUSION: The strategy of using conventional-dose IV
      rTPA and the sequential combination of IA UK in patients without an early
      clinical response to IV treatment was safe and feasible. This strategy achieved
      high complete arterial recanalization rates and good functional outcomes.

PMID- 15502124
TI  - MR safety and imaging of neuroform stents at 3T.
AB  - The Neuroform stent is a self-expanding nitinol stent designed for use in wide
      necked intracranial aneurysms. Heating and imaging artifacts were evaluated by
      using a porcine carotid artery aneurysm model in a 3T MR system. A suspended
      Neuroform stent was tested for deflection. No heating was measured, and no
      evidence of deflection of the stent was found. Imaging artifacts were minimal. MR
      imaging in patients with Neuroform stent-treated aneurysms is safe and feasible.

PMID- 15502125
TI  - Increased intracranial volume: a clue to the etiology of idiopathic normal
      pressure hydrocephalus?
AB  - BACKGROUND AND PURPOSE: The etiology of idiopathic normal-pressure hydrocephalus
      (NPH) is unknown. The purpose of this study was to examine the hypothesis that
      NPH begins in infancy as benign external hydrocephalus due to decreased uptake of
      CSF by the arachnoid villi. Since this occurs before the sutures fuse, a
      secondary hypothesis is that the intracranial volumes of patients with NPH should
      be larger than those of healthy individuals. METHODS: Intracranial volumes of 51
      patients with clinically suspected NPH were compared with those of age- and sex
      matched control subjects. All patients underwent phase-contrast CSF velocity MR
      imaging. They had aqueductal CSF stroke volumes of at least 60 microL, which was
      50% higher than previously published normal values. Intracranial volumes were
      measured and compared between groups. RESULTS: The average intracranial volume
      for men with NPH (n = 22) was 1682 mL compared with 1565 for male control
      subjects (n = 55). The NPH volume averaged 118 mL (7.5%) larger than the control
      volume (P = .003). The average intracranial volume for women with NPH (n = 29)
      was 1493 mL compared with 1405 mL for female control subjects (n = 55). The NPH
      volume was 88 mL (6.3%) larger than the control volume (P = .002). CONCLUSION:
      Patients with NPH have intracranial volumes significantly larger than normal,
      suggesting that the initial insult occurs before the sutures fuse at 1 year of
      age. The patients somehow remain asymptomatic until their later years, when a
      second insult must occur, leading to symptomatic NPH.

PMID- 15502126
TI  - Multi-section CT angiography for detection of cerebral aneurysms.
AB  - BACKGROUND AND PURPOSE: Multi-section CT has great potential for use in vascular
      studies. Our purpose was to determine the accuracy of multi-section CT
      angiography in detecting cerebral aneurysms compared with digital subtraction
      angiography or surgery. METHODS: One hundred consecutive patients who underwent
      multi-section CT angiography and either digital subtraction angiography or
      surgery were included in the study. Multi-section CT angiography and digital
      subtraction angiography results were evaluated independently by different
      neuroradiologists who performed aneurysm detection, quantitation, and
      characterization by using 2D multiplanar reconstructions, 3D maximum intensity
      projection, and volume-rendered techniques. RESULTS: When using intra-arterial
      digital subtraction angiography or surgery, 113 aneurysms (true positives and
      false negatives) were detected in 83 of the 100 patients. A total of 106
      aneurysms (true positives) were confirmed by using digital subtraction
      angiography or surgery, or both. Seven aneurysms were missed when using multi
      section CT angiography. Eight aneurysms were not confirmed by digital subtraction
      angiography and were considered to be false positive evaluations. The sensitivity
      for detecting aneurysms < 4 mm, 4 to 10 mm, and > 10 mm on a per-aneurysm basis
      was 0.84 (95% confidence interval: 0.72, 0.92), 0.97 (95% confidence interval:
      0.91, 0.99), and 1.00 (95% confidence interval: 0.88, 1.00), respectively. The
      sensitivity, specificity, and accuracy of multi-section CT angiography for
      detecting aneurysms on a per-patient basis were 0.99 (95% confidence interval:
      0.96, 1.00), 0.88 (95% confidence interval: 0.69, 0.94), and 0.98 (95% confidence
      interval: 0.95, 1.00), respectively. CONCLUSION: Multi-section CT angiography has
      a high sensitivity in detecting aneurysms (especially aneurysms > 3 mm). However,
      CT angiography is currently not sensitive enough to replace digital subtraction
      angiography.

PMID- 15502127
TI  - Role of multisection CT angiography in the evaluation of vertebrobasilar
      vasospasm in patients with subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: Optimal means for assessing cerebral vasospasm, mainly at
      the vertebrobasilar system, have not been established. The purpose of this study
      was to evaluate the role of multisection CT angiography (MCTA) in the detection
      and quantification of vertebrobasilar vasospasm (VBS) indicated on transcranial
      Doppler (TCD) imaging in patients with subarachnoid hemorrhage (SAH). METHODS:
      Forty-three MCTA studies of the vertebrobasilar arteries were performed with a
      multisection spiral CT scanner in 36 patients with SAH. Parameters used were 1-mm
      collimation, 0.625Q pitch, 120 kV, and 250 mAs. Contrast material was injected
      (80-100 mL, 3 mL/s) after a 15-20-second delay. Postprocessing of the
      vertebrobasilar system was performed by using maximum intensity projection and
      volume-rendering reconstruction. Vessel diameter was measured at different
      intracranial locations along the vertebral and basilar arteries perpendicular to
      their long axis by using curved reformatted multiplanar reformation. TCD imaging
      of the posterior circulation was performed within 24 hours. RESULTS: MCTA
      demonstrated narrowed arteries compatible with VBS in 13 patients, consistent
      with TCD findings. Despite TCD recordings of high flow velocity in three other
      patients, MCTA did not reveal vasospasm but did show wide arteries feeding
      arteriovenous malformations in two and normal-sized arteries in one. VBS in two
      patients was identified on MCTA but overlooked during TCD imaging. Twenty
      patients had normal findings on both TCD and MCTA studies. CONCLUSION: Cerebral
      MCTA is recommended as a reliable, rapid, and minimally invasive diagnostic
      method, one complementary to TCD imaging for assessing VBS in patients with SAH.

PMID- 15502128
TI  - Multiparametric iterative self-organizing MR imaging data analysis technique for
      assessment of tissue viability in acute cerebral ischemia.
AB  - BACKGROUND AND PURPOSE: Defining viability and the potential for recovery of
      ischemic brain tissue can be very valuable for patient selection for acute stroke
      therapies. Multiparametric MR imaging analysis of ischemic lesions indicates that
      the ischemic lesion is inhomogeneous in degree of ischemic injury and recovery
      potential. We sought to define MR imaging characteristics of ischemic lesions
      that are compatible with viable tissue. METHODS: We included patients with
      supratentorial ischemic stroke who underwent multiparametric MR imaging studies
      (axial multi-spin-echo T2-weighted imaging, T1-weighted imaging, and diffusion
      weighted imaging) at the acute (< 24 hours) and outcome (3 months) phases of
      stroke. Using the algorithm Iterative Self-Organizing Data Analysis Technique
      (ISODATA), the lesion was segmented into clusters and each was assigned a number,
      called the tissue signature (white matter = 1, CSF = 12, all others between these
      two). Recovery was defined as at least a 20% size reduction from the acute phase
      ISODATA lesion volume to the outcome phase T2-weighted imaging lesion volume. The
      tissue signature data were collapsed into the following categories: < or = 3, 4,
      5, and > or = 6. Logistic regression analysis included the following parameters:
      lesion volume, tissue signature value, apparent diffusion coefficient (ADC)
      value, relative ADC (rADC) expressed as a ratio, T2 value, and T2 ratio. The
      model with the largest goodness of fit value was selected. RESULTS: We included
      48 patients (female-male ratio, 26:22; age, 64 [+/-14] years; 15 treated with
      recombinant tissue plasminogen activator [rt-PA] within 3 hours of onset; median
      National Institutes of Health Stroke Scale score, 7 [range, 2-26]). Median
      symptom onset-to-MR imaging time interval was 9.5 hours. With ISODATA processing,
      we generated 200 region-of-interest tissue records (one to nine tissue records
      per patient). Regarding tissue recovery, we detected a three-way interaction
      among ADC, ISODATA tissue signature, and previous treatment with rt-PA (P =
      .003). In the group not treated with rt-PA, ischemic tissues with acute rADC
      greater than the median (0.79) and tissue signature < or = 4 were more likely to
      recover (80% vs. 31% and 13%, odds ratio [95% CI]: 0.12 [0.05, 0.30] and 0.04
      [0.01, 0.18] for tissue signatures 5 and 6, respectively). CONCLUSION: ISODATA
      multiparametric MR imaging of acute stroke clearly shows inhomogeneity and
      different viability of the ischemic lesion. Ischemic tissues with lower acute
      phase ISODATA tissue signature values (< or = 4) and higher rADC values (> or =
      0.79) are much more likely to recover than those with higher signature values or
      lower rADC values. The effect of these factors on tissue recovery, however, is
      dependent on whether preceding treatment with rt-PA had been performed. Our
      approach can be a valuable tool in the design of therapeutic stroke trials with
      an extended time window.

PMID- 15502129
TI  - Detection of corticospinal tract compromise in amyotrophic lateral sclerosis with
      brain MR imaging: relevance of the T1-weighted spin-echo magnetization transfer
      contrast sequence.
AB  - BACKGROUND AND PURPOSE: Hyperintensity in the posterior limb of the internal
      capsule at T2-weighted MR imaging, consistent with corticospinal tract (CST)
      degeneration, is described in amyotrophic lateral sclerosis (ALS). However, the
      lack of specific tests or biological markers hinders confirmation of the
      diagnosis, especially in the early stages. We investigated the CST in ALS with MR
      imaging. METHODS: We examined 25 patients (14 men, 11 women; mean age, 49.1
      years; range, 29-68 years) and 21 age- and sex-matched control subjects without
      upper motor neuron signs. According to the revised El Escorial criteria, 22
      patients had definite ALS; two, probable ALS; and one, suspected ALS. Fluid
      attenuated inversion recovery (FLAIR; TR/TE/TI, 11,000/140/2600) and T1-weighted
      spin-echo (SE)/magnetization transfer contrast-enhanced (MTC; TR/TE, 510/12)
      imaging was performed at 1 T. Two experienced neuroradiologists blinded to the
      patients' history independently evaluated the CST. RESULTS: T1-weighted SE MTC
      imaging allowed visualization of the CST in both patients and control subjects.
      T1-weighted SE MTC images showed hypointensity along the CST and bilateral
      subcortical regions of the precentral gyri in all control subjects and
      hyperintensity in 80% of patients with ALS (P < .05). FLAIR images showed
      hyperintensity in these areas in both groups, with no significant difference.
      CONCLUSION: T1-weighted SE MTC imaging is sensitive and accurate in depicting CST
      lesions in ALS, whereas FLAIR imaging is not. T1-weighted SE MTC imaging is
      useful in diagnosing ALS by showing hyperintense areas along the CST, which
      separates patients from control subjects. This sequence should be included in the
      workup of patients with weakness and pyramidal signs.

PMID- 15502130
TI  - Is the subthalamic nucleus hypointense on T2-weighted images? A correlation study
      using MR imaging and stereotactic atlas data.
AB  - BACKGROUND AND PURPOSE: Although the subthalamic nucleus is the most frequently
      used target for surgical treatment of Parkinson's disease, the criteria on which
      it can be identified on T2-weighted images have never been clearly defined. This
      study was conducted to characterize the precise anatomic distribution of T2
      weighted hyposignal in the subthalamic region and to correlate this hyposignal
      with iron content in the subthalamic nucleus. METHODS: The T2-weighted MR imaging
      acquisitions of 15 patients with Parkinson's disease were fused with a digitized
      version of the Schaltenbrand and Wahren anatomic atlas. The MR signal intensity
      within the anatomic limits of the subthalamic nucleus was evaluated. An anatomic
      specimen obtained at autopsy was used to evaluate iron content. RESULTS: In all
      patients, the subthalamic nucleus was hypointense on both sides in the anterior
      half of the nucleus. At more posterior levels of the nucleus, hypointensity was
      less frequently observed (20-80%). Hypointensity was never observed at the most
      posterior pole. Iron was present in the anteromedial part of the nucleus but
      absent at the most posterior levels. CONCLUSION: The hypointense signal intensity
      located lateral to the red nucleus and dorsolateral to the substantia nigra
      correlates with the presence of iron and corresponds anatomically to the
      subthalamic nucleus. It can therefore be used as a landmark for electrode
      implantation in patients with Parkinson's disease. It should, however, be
      emphasized that although hypointensity was always present in the anterior half of
      the subthalamic nucleus, the posterior part of the nucleus was not visible in
      most cases.

PMID- 15502131
TI  - Characterization of a first-pass gradient-echo spin-echo method to predict brain
      tumor grade and angiogenesis.
AB  - BACKGROUND AND PURPOSE: No widespread clinical method provides specific
      information about the angiogenic characteristics of gliomas. We characterized
      blood volume and vascular morphologic parameters from combined gradient-echo (GE)
      and spin-echo (SE) MR imaging and assessed their relationship to tumor grade, a
      known correlate of glioma angiogenesis. METHODS: Simultaneous GE and SE echo
      planar imaging was performed with bolus gadolinium administration (0.20-0.25
      mmol/kg) in 73 patients with glioma. To diminish possible T1 changes due to
      contrast agent extravasation, a preload (0.05-0.10 mmol/kg) was administered
      before the study, and a postprocessing correction algorithm was applied. Image
      maps of total (GE) and microvascular (SE) relative cerebral blood volume (rCBV)
      and the mean vessel diameter (mVD) calculated from the ratio of GE and SE
      relaxation rate changes (DeltaR2*/DeltaR2) were compared with tumor grade. A
      nonparametric K nearest-neighbor decision rule was applied to determine if the
      combined data could be used to distinguish low-grade (I-II) from high-grade (III
      IV) tumors on a per-patient basis. RESULTS: For whole tumors, significant
      correlations were found between GE rCBV and grade (P < .0001) and between mVD and
      grade (P = .0001) but not between SE rCBV and grade (P = .08). For areas of
      highest SE rCBV (microvascular hotspots), SE rCBV and tumor grade were
      significantly correlated (P = .0007). In terms of differentiation, 69% of low
      grade tumors and 96% of high-grade tumors were correctly classified. CONCLUSION:
      Combined GE and SE MR imaging provides information consistent with neoplastic
      angiogenesis, demonstrating its potential to aid in optimizing treatments,
      categorizing lesions, and influencing patient care.

PMID- 15502132
TI  - Glioblastoma multiforme causing calvarial destruction: an unusual manifestation
      revisited.
AB  - This report describes invasion of overlying calvaria and soft tissues by a high
      grade glioma without macroscopic evidence of dural involvement. The initial
      radiologic examinations demonstrated a heterogeneous mass in the right
      frontoparietal region with both extra- and intra-axial components. Inward
      displacement of the adjacent dura initially prompted consideration for extra
      axial lesions such as metastatic lesions, lymphoma, or an aggressive meningioma.
      The pathologic findings demonstrated a glial cell origin.

PMID- 15502133
TI  - Pineal cystic germinoma with syncytiotrophoblastic giant cells mimicking MR
      imaging findings of a pineal cyst.
AB  - We report a case of precocious puberty in a 4-year-old boy. Contrast-enhanced T1
      weighted MR imaging suggested a pineal cyst with enhancement of the slightly
      thickened wall and focal wall irregularity. Three-dimensional constructive
      interference in a steady-state imaging revealed a focal lobulation and a nodule
      like area in the lesion. The lesion mimicking a pineal cyst proved to be a
      germinoma with syncytiotrophoblastic giant cells, on the basis of biopsy and
      tumor marker results.

PMID- 15502134
TI  - Reversible MR angiographic findings in a patient with autoimmune Graves disease.
AB  - A 45-year-old woman presented with subacute encephalopathy due to autoimmune
      Graves disease. MR angiography (MRA) demonstrated stenosis of the major
      intracerebral arteries. After high-dose methylprednisolone therapy and
      plasmapheresis, her neurologic status improved dramatically, and the MRA findings
      resolved after 3 months. The angiographic findings in Graves disease that
      resemble those in Moyamoya disease are temporary.

PMID- 15502135
TI  - An unusual cause of visual loss: involvement of bilateral lateral geniculate
      bodies.
AB  - We report the clinical and radiologic features of a 31-year-old woman who
      suffered incongruous binasal and bitemporal visual field defects and severe
      sudden visual loss due to hypoperfusion of bilateral lateral geniculate bodies
      following anaphylactic shock induced by 500 mg amoxicillin per os. Complete
      neuroophthalmologic examinations were performed regularly for visual acuity,
      color vision, pupillary reflexes, and visual fields. Additional testing was
      performed by means of MR imaging of the brain and CSF analysis. Follow-up was
      performed for 12 months. Vision loss was acute and severe, its onset bilateral
      and simultaneous. The patient recovered visual acuity of 1.0 within 7 weeks.
      Color vision was abnormal in both eyes but gradually improved to normal. Visual
      fields were characterized by incongruous binasal and bitemporal defects, but they
      reduced progressively. Cerebral MR imaging confirmed the presence of symmetrical
      lesions confined exclusively within both lateral geniculate bodies. These lesions
      were best seen on T1-weighted and fluid-attenuated inversion recovery images as
      high-signal-intensity areas suggestive of hemorrhagic ischemia. CSF analysis was
      normal and aseptic. Blood tests and cultures excluded any microbial infection. We
      conclude that shock may induce a bilateral isolated ischemia of the lateral
      geniculate bodies, resulting in incongruous binasal and bitemporal visual field
      defects and severe visual loss. MR imaging is the optimal imaging technique to
      confirm the diagnosis and for follow-up.

PMID- 15502136
TI  - Atypical MR imaging perfusion in developmental venous anomalies.
AB  - Developmental venous anomalies (DVAs) are common variants of cerebral venous
      drainage that are typically incidental findings on contrast-enhanced MR imaging
      studies. We present four cases of asymptomatic DVAs that demonstrate increased
      cerebral blood flow, cerebral blood volume, mean transit time, and time to peak
      on perfusion MR images. Our study indicates that alterations in perfusion MR
      imaging parameters can be seen with uncomplicated DVAs and do not necessarily
      imply a more ominous underlying etiologic factor, such as hypervascular tumor or
      stroke.

PMID- 15502137
TI  - Serial evaluation of diffusion tensor brain fiber tracking in a patient with
      severe diffuse axonal injury.
AB  - Serial evaluation of diffusion tensor brain fiber tracking was performed in a 27
      year-old female patient with diffuse axonal injury after a traffic accident.
      Although the result of brain fiber tracking was not necessarily parallel to her
      clinical symptoms, it may have predicted the neurologic prognosis.

PMID- 15502138
TI  - Intracranial MR venography in children: normal anatomy and variations.
AB  - BACKGROUND AND PURPOSE: Little information is available regarding the anatomy of
      the intracranial veins and sinuses that can be shown on MR venograms of children.
      The aim of this study was to determine the normal venous anatomy and anatomic
      variants. METHODS: Fifty children who were referred for investigation of
      developmental delay and who had normal results of MR imaging of the brain were
      recruited into the study. The cerebral veins and sinuses, including the occipital
      sinuses, were assessed by using 2D time-of-flight venography. Particular
      attention was paid to the anatomy of the venous confluence. RESULTS: Twenty-seven
      cases had dominant right transverse sinuses, 18 had dominant left transverse
      sinuses, four had co-dominant transverse sinuses, and one had absence of both
      transverse sinuses. In 21 (51%) of 41 cases without occipital sinuses, absent or
      hypoplastic transverse sinuses were found. Nine patients had occipital sinuses.
      Five (56%) of nine patients with occipital sinuses were younger than 2 years, and
      patients younger than 2 years accounted for 24% of all patients (12 of 50
      patients) in the study. In six (67%) of nine patients with occipital sinuses,
      absent or hypoplastic transverse sinuses were shown. Two patients had bulbous
      prominence of the vein of Galen. One had foreshortened superior sagittal sinus,
      which in turn is drained by two paramedian cortical veins. CONCLUSION:
      Understanding the normal anatomy of the cerebral venous system and its variants
      by using MR venography in children provided the background to future studies on
      anomalous venous structure in malformations of the brain.

PMID- 15502139
TI  - Contribution of fetal MR imaging in the evaluation of cerebral ischemic lesions.
AB  - BACKGROUND AND PURPOSE: Little is known about the different patterns of fetal
      cerebral ischemic lesions at MR imaging. Our purpose was to evaluate the
      contribution of MR imaging in the evaluation of such lesions by correlating the
      results with ultrasonography (US) and neurofetopathologic (NFP) findings.
      METHODS: We examined 28 fetuses (mean, 28 weeks' gestation) with cerebral
      ischemic lesions on NFP examination. MR findings were correlated with US and NFP
      results with regard to the depiction of gyration and parenchymal abnormalities.
      RESULTS: MR imaging added to US findings in 24 cases by revealing lesions
      (gyration abnormalities, parenchymal lesions). These results were either
      overlooked during US (n = 16) or more extensive than expected with US (n = 8). MR
      findings were always confirmed by NFP. NFP yielded additional findings for 14
      lesions that were overlooked during MR imaging (n = 4) or that were more
      extensive than expected with MR imaging (n = 10). T1-, T2-, and T2*-weighted MR
      patterns of different lesions (cavitations, gliosis, softening of the white
      matter, laminar necrosis, calcified leukomalacia, old hemorrhage) were
      identified. CONCLUSION: MR imaging is a valuable tool in the evaluation of fetal
      brain ischemia. The results of this study emphasize the role of the different
      sequences (T1-, T2-, T2*-weighted) required to detect fetal cerebral ischemic
      lesions. MR imaging is more accurate in the detection of small focal lesions than
      in the evaluation of diffuse white matter abnormalities.

PMID- 15502140
TI  - Diffusion tensor images in children with early-treated, chronic, malignant
      phenylketonuric: correlation with intelligence assessment.
AB  - BACKGROUND AND PURPOSE: Diffusion tensor (DT) images can provide information
      about the nature of white matter changes, including axonal loss and
      demyelination. We applied DT imaging to verify white matter changes in patients
      with malignant phenylketonuria (PKU) and to correlate the findings with clinical
      intelligence quotients (IQs). METHODS: We compared DT images with T2-weighted
      images in 12 patients with early-treated, chronic, stable malignant PKU and 12
      age-matched control subjects. DT parameters included first, second, and third
      eigenvalues (EV1-3), apparent diffusion coefficients (ADCs), and fractional
      anisotropy (FA). Regions of interest were placed the frontoparietal, parieto
      occipital, frontal and central white matter and in the anterior and posterior
      corpus callosum. Eight patients older than 3 years underwent IQ assessment
      including verbal, performance, and full-scale IQ tests. RESULTS: In the eight
      patients older than 3 years, no definite abnormal signal intensity changes were
      found on T2-weighted images. EV2, EV3, and FA of the parieto-occipital white
      matter were significantly different in patients and control subjects older than 3
      years. EV3 and ADC of the parieto-occipital white matter were significantly and
      negatively correlated with verbal IQ (r = -0.79, P = .04) and performance IQ (r =
      -0.93, P = .03). FA of the parieto-occipital central white matter was positively
      correlated with verbal IQ (r = 0.75, P = .05). CONCLUSION: Though treated early,
      patients with chronic, stable malignant PKU had abnormal DT findings in the
      parieto-occipital central white matter. EV2, EV3, and FA maps are potential tools
      for demonstrating brain changes due to malignant PKU.

PMID- 15502141
TI  - Abnormal hippocampal development in children with medulloblastoma treated with
      risk-adapted irradiation.
AB  - BACKGROUND AND PURPOSE: Children with medulloblastoma demonstrate post-treatment
      neurocognitive deficits in a number of areas, including memory performance.
      However, there is no definitive understanding of the neuropathology underlying
      these functional deficits. Previous literature has reported that hippocampal
      integrity is crucial to the acquisition of new episodic memories. Therefore, we
      hypothesized that longitudinal hippocampal volume measurements are abnormal in
      patients with medulloblastoma and thereby provide a possible substrate for
      explaining memory dysfunction. METHODS: Twenty-five pediatric patients underwent
      159 serial MR imaging examinations (mean = six examinations per patient) for up
      to 5 years after irradiation and chemotherapy treatment for medulloblastoma.
      Right and left hippocampal volumes were obtained by manually tracing 1.5-mm
      contiguous coronal sections through the structure. Random coefficient models were
      used to examine longitudinal change in hippocampal volume as a function of time
      after diagnosis. RESULTS: Both right and left hippocampal volumes initially
      decreased after treatment. This abnormal volume pattern continued until
      approximately 2-3 years after diagnosis, when hippocampal volumes returned toward
      a normal positive growth pattern. Volume loss occurred predominately in the
      posterior regions. Female sex, low parental education, shunt placement, and
      positive seizure history all had a significant negative impact on hippocampal
      volume. CONCLUSION: Pediatric medulloblastoma survivors demonstrate an abnormal
      pattern of hippocampal volume development after treatment. Radiation dose mapping
      may expand our understanding of region-specific changes in hippocampal volume.
      Further exploration of the relationships between radiation therapy, memory
      dysfunction, and hippocampal pathology in this population is warranted.

PMID- 15502142
TI  - Percutaneous CT-guided biopsy of osseous lesion of the spine in patients with
      known or suspected malignancy.
AB  - BACKGROUND AND PURPOSE: CT-guided spinal biopsy (CTGSB) is considered a safe and
      accurate procedure. Our goal was to determine the accuracy of a CTGSB of osseous
      spinal lesions in patients with known or suspected underlying malignancy in
      reference to major variables such as the radiographic appearance of the biopsied
      lesion and its location within the spinal column. METHODS: We retrospectively
      reviewed results of 410 consecutive percutaneous CTGSB procedures of osseous
      spinal lesions. Biopsy was determined to be adequate if diagnostic tissue was
      obtained (n = 401) or unsatisfactory (n = 9) if only blood without cellular
      elements was present on final pathologic-cytologic examination. RESULTS: The
      level of spinal biopsy was cervical in nine patients (2%), thoracic in 123 (31%),
      lumbar in 164 (42%), and sacral in 96 (25%). The overall diagnostic accuracy of
      CTGSB was 89%, with a false-negative rate of 11%. Biopsy of lytic lesions yielded
      an accurate diagnosis in 93% (220 of 236). Despite technical challenges inherent
      to biopsy of sclerotic lesions, diagnostic accuracy was 76% (63 of 83), although
      more importantly, 24% (20 of 83) of the results in sclerotic lesions were falsely
      negative. CONCLUSION: CTGSB of osseous spinal lesions is an important tool in the
      workup of patients with known or suspected underlying neoplastic disease.
      However, a negative result must be confirmed with either close follow-up or,
      preferably, open biopsy, especially in cases of sclerotic lesions for which
      diagnostic accuracy is decreased and the false-negative rate is high.

PMID- 15502143
TI  - Use of radio-frequency ablation for the palliative treatment of sacral chordoma.
AB  - Chordomas are the most common sacrococcygeal tumors in adults. They have a high
      recurrence rate, are locally aggressive, and are resistant to radiation therapy.
      Radio frequency is a relatively new therapeutic technique, used primarily in the
      treatment of liver tumors; however, its application has widened to include other
      neoplasms. We report its use in the palliative treatment of chordomas in two
      patients for debulking and control of pain, with good results and low morbidity.

PMID- 15502144
TI  - Selective lumbar nerve root blocks with CT fluoroscopic guidance: technique,
      results, procedure time, and radiation dose.
AB  - CT fluoroscopy may be used as a rapid and effective means of guiding needle
      placement when performing selective lumbar nerve root blocks. In this set of
      patients, the average external radiation dose was 0.73 mrem per procedure, with
      an average of 2 seconds of CT-fluoroscopy time and four images per procedure.
      Average physician room time was 7 minutes. Use of intermittent CT fluoroscopy
      during lumbar selective nerve root blocks can result in minimal radiation dose
      levels and procedure times that are comparable to fluoroscopic guidance.

PMID- 15502145
TI  - A technique to circumvent subcutaneous cement tracts during percutaneous
      vertebroplasty.
AB  - The deposition of a subcutaneous cement tract is a potential complication of
      percutaneous vertebroplasty. These tracts can be a source of pain and tenderness
      for the patient. We describe a case of symptomatic cement deposition within a
      needle tract in the subcutaneous tissues that required surgical removal, and we
      describe a technique to prevent this complication in a second patient, by using
      needle redirection to cut across the cement core.

PMID- 15502146
TI  - Unilateral transpedicular course of an ascending lumbar vein through a pedicular
      foramen mimicking a lytic lesion: an anatomic variant.
AB  - An ascending lumbar vein passing through a foramen on the right pedicle of the
      third lumbar vertebra unilaterally, which was diagnosed incidentally during
      virtual CT colonoscopy of a patient with a rectal tumor, is described.
      Recognition of this anatomic variation is important to avoid diagnostic
      misinterpretations and transpedicular interventions such as percutaneous
      vertebroplasty or surgical instrumentation that may result in excessive
      hemorrhage and inadvertent leak of cement when it is present.

PMID- 15502147
TI  - Familial amyloid polyneuropathy: hypertrophy of ligaments supporting the spinal
      cord.
AB  - We describe characteristic spinal MR findings of two cases of familial amyloid
      polyneuropathy (FAP). Both cases showed leptomeningeal enhancement on contrast
      enhanced T1-weighted image. In addition, three-dimensional constructive
      interference in steady-state imaging demonstrated thickening of the ligaments,
      other connective tissues within the spinal canal, dura matter, and dorsal nerve
      roots. These findings in FAP are felt to represent amyloid deposition.

PMID- 15502148
TI  - CT-guided aspirations in the head and neck: assessment of the first 216 cases.
AB  - BACKGROUND AND PURPOSE: The growth of cross-sectional imaging has increased the
      detection of nonpalpable head and neck masses. We sought to determine the
      reliability of CT-guided fine-needle aspiration (FNA) over 216 consecutive cases.
      METHODS: We retrospectively reviewed histopathologic findings and notes from 216
      consecutive head and neck CT-guided FNA procedures performed between 1993 and
      2003. Types of needles used, passes required, lesion location, initial cytologic
      diagnosis, and final histopathologic or clinical diagnosis were reviewed.
      RESULTS: Diagnostic samples were obtained in 195 (90.3%) of the lesions, with 21
      (9.7%) inadequate samples. A correct diagnosis was made in 191 cases (88.4%).
      Final FNA diagnosis was discordant in four (1.9%) specimens, with the
      parapharyngeal space and parotid gland having the highest rate of inaccuracy. The
      range in number of passes required for final diagnosis was one to six (mode, 2.0
      passes per specimen; median, 2.0; mean, 2.6; standard deviation, 1.13). In 135
      (63%) of 216 cases, definitive surgical pathologic results, including findings
      for the four discordant specimens, were obtained. Of the nondiagnostic specimens,
      six (29%) of 21 went to surgery, five (83%) of six were neoplastic, and one (17%)
      of six was fibrous tissue. The remainder underwent clinical and imaging follow
      up. CONCLUSION: CT-guided FNA is a safe, well tolerated, and accurate for the
      diagnosis of head and neck lesions. In our series, the percentage of diagnostic
      samples obtained improved compared with prior reports. The low diagnostic error
      rate overall was possibly related to onsite evaluation by the cytopathologist and
      to improved FNA technique.

PMID- 15502149
TI  - Ultrasonography-guided core-needle biopsy of parotid gland masses.
AB  - BACKGROUND AND PURPOSE: An accurate diagnosis of a parotid gland mass is
      essential for adequate management. We determined the clinical efficacy of USCNB
      in diagnosing parotid gland masses by using cutting needles of different bores.
      METHODS: We reviewed records for 40 benign and 13 malignant parotid lesions.
      USCNB was performed by using 14-20-gauge needles (mean, 16.6 gauge) with one to
      five (mean, 2.43) passes and a 15-mm throw or specimen notch. Final diagnoses
      were established on the basis of surgicopathologic results in 31 cases, and on
      the basis of histopathologic analysis of biopsy specimens, clinical data, and/or
      imaging studies in 22, with a follow-up of 12.2-77.5 months (mean, 33.6 months).
      RESULTS: Compared with surgicopathology, USCNB had a sensitivity of 83%, a
      specificity of 100%, and an accuracy of 97% in providing specific tissue
      diagnoses and in differentiating malignant from benign masses. Its positive and
      negative predictive values were 100% and 96%, respectively, in diagnosing
      malignancy. One patient (2%) had a local hematoma without sequela after surgical
      removal of a Warthin tumor. Core biopsy results were completely concordant with
      surgical findings in 30 (97%) of 31 cases. CONCLUSION: USCNB is a safe and
      efficient diagnostic procedure with an accuracy of 97% in the pathologic
      diagnosis of parotid masses. It can be performed in an outpatient clinic and
      enables specific tissue diagnosis to obviate intraoperative frozen biopsy and
      unnecessary surgery. An 18-gauge needle is sufficient for accurate and specific
      tissue diagnosis of parotid masses.

PMID- 15502150
TI  - The incidence of concha bullosa and its relationship to nasal septal deviation
      and paranasal sinus disease.
AB  - BACKGROUND AND PURPOSE: The incidence of middle turbinate pneumatization, or
      concha bullosa, has been well described in the literature. However, to our
      knowledge, no study has evaluated concha bullosa in relation to nasal septal
      deviation. We sought to analyze the incidence of concha bullosa and any
      correlation with nasal septal deviation and paranasal sinus disease. METHODS:
      Three neuroradiologists retrospectively reviewed findings of 1095 consecutive
      paranasal sinus CT studies conducted between 2001 and 2002. All examinations were
      performed for evaluation of a symptom referable to the sinonasal region.
      Paranasal sinus inflammatory disease was identified and graded as mild, moderate,
      or severe. Sphenoid, ethmoid, maxillary, and frontal sinuses were each graded
      separately on both sides. If a concha bullosa was present, it was graded in size
      as small, moderate, or large. If bilateral concha were present, sizes were
      compared and when one was larger, it was identified as dominant. When nasal
      septal deviation was present, it was graded as mild, moderate, or severe. The
      direction of nasal septal deviation was identified as the face of the convex
      surface. RESULTS: There was a clear association between the presence of a
      unilateral concha, or a dominant concha (in the case of bilateral concha), and
      the presence of nasal septal deviation (P < .0001). Moreover, there was a
      significant relationship between the presence of concha bullosa and deviation of
      the nasal septal to the contralateral side (P < .0001). This inverse association
      was present regardless of the size of the concha bullosa or degree of septal
      deviation. In every case, there was some preservation of air channels between the
      dominant concha and the nasal septum. Seventy-three percent of patients with
      concha bullosa had paranasal sinus inflammatory disease; 78% of patients without
      concha bullosa also had some form of inflammatory disease. CONCLUSION: Concha
      bullosa is a common anatomic variant. There is a strong association between the
      presence of a concha bullosa and contralateral deviation of the nasal septum.
      Nasal septal deviation away from the dominant concha, with preserved adjacent air
      channels, suggests that the deviation is not a direct result of mass effect from
      the concha. No increased incidence of paranasal sinus disease exists in patients
      with concha bullosa.

PMID- 15502151
TI  - Type I proatlantal artery with bilateral absence of the external carotid
      arteries.
AB  - During color Doppler examination of a 41-year-old man who presented with vertigo,
      a right vertebral artery could not be found. Both MR angiography and digital
      subtraction angiography revealed a large anastomotic vessel between the right
      internal carotid and vertebral artery. It was thought to be type I proatlantal
      artery. Furthermore, the external carotid arteries were bilaterally absent.
      Although each vascular anomaly mentioned above is rare, it even more rare for
      these variations to occur simultaneously.

PMID- 15502152
TI  - Bilateral persistence of type 1 proatlantal arteries: report of a case and review
      of the literature.
AB  - Persistent proatlantal artery type 1 is one of the four anastomotic vessels
      between the carotid and vertebrobasilar arterial systems. Persistence of this
      embryonic anastomosis is extremely rare. We present such a case with bilateral
      persistent proatlantal arteries that arose from internal carotid arteries,
      entered the skull via the foramen magnum and united with the horizontal portions
      of vertebral arteries. We also mention its embryology, potential clinical
      implications, and differentiating features between two types of proatlantal
      arteries.

PMID- 15502154
TI  - 3-T MR imaging: ready for clinical practice.

PMID- 15502155
TI  - The time for 3T clinical imaging is now.

PMID- 15502156
TI  - Complex formation and catalytic activation by the PII signaling protein of N
      acetyl-L-glutamate kinase from Synechococcus elongatus strain PCC 7942.
AB  - The signal transduction protein P(II) from the cyanobacterium Synechococcus
      elongatus strain PCC 7942 forms a complex with the key enzyme of arginine
      biosynthesis, N-acetyl-l-glutamate kinase (NAGK). Here we report the effect of
      complex formation on the catalytic properties of NAGK. Although pH and ion
      dependence are not affected, the catalytic efficiency of NAGK is strongly
      enhanced by binding of P(II), with K(m) decreasing by a factor of 10 and V(max)
      increasing 4-fold. In addition, arginine feedback inhibition of NAGK is strongly
      decreased in the presence of P(II), resulting in a tight control of NAGK activity
      under physiological conditions by P(II). Analysis of the NAGK-P(II) complex
      suggests that one P(II) trimer binds to one NAGK hexamer with a K(d) of
      approximately 3 nm. Complex formation is strongly affected by ATP and ADP. ADP is
      a strong inhibitor of complex formation, whereas ATP inhibits complex formation
      only in the absence of divalent cations or in the presence of Mg(2+) ions,
      together with increased 2-oxoglutarate concentrations. Ca(2+) is able to
      antagonize the negative effect of ATP and 2-oxoglutarate. ADP and ATP exert their
      adverse effect on NAGK-P(II) complex formation through binding to the P(II)
      protein.

PMID- 15502157
TI  - EphrinB1 is essential in T-cell-T-cell co-operation during T-cell activation.
AB  - Eph kinases are the largest family of receptor tyrosine kinases, and their
      ligands are ephrins (EFNs), which are also cell surface molecules. We have very
      limited knowledge about the expression and function of these kinases and their
      ligands in the immune system. In this study we investigated the effect of EFNB1
      on mouse T-cells. EFNB1 and the Eph kinases it interacts with (collectively
      called EFNB1 receptors (EFNB1R)) were expressed on T-cells, B cells, and
      monocytes/macrophages. Some T-cells were double positive for EFNB1 and EFBB1R.
      Solid phase EFNB1 in the presence of suboptimal TCR ligation augmented T-cell
      responses in terms interferon-gamma secretion, proliferation, and cytotoxic T
      lymphocyte activity but not interleukin-2 production. After T-cell receptor (TCR)
      ligation, EFNB1R congregated to TCR caps, and then both of them translocated to
      raft caps. This provides a morphological basis for EFNB1R to enhance TCR
      signaling. Further downstream of the signaling pathway, EFNB1R stimulation led to
      increased LAT (linker for activation of T-cells) phosphorylation and p44/42 and
      p38 MAPK activation. Similar to CD28 costimulation, EFNB1R costimulation was
      insensitive to cyclosporin A inhibition. On the other hand, unlike the former,
      EFNB1R costimulation failed to activate Akt, which is essential in triggering
      interleukin-2 production. Our study suggests that EFNB1 is pivotal in T-cell-T
      cell costimulation and in reducing T-cell response threshold to antigen
      stimulation.

PMID- 15502158
TI  - von Hippel-Lindau partner Jade-1 is a transcriptional co-activator associated
      with histone acetyltransferase activity.
AB  - Jade-1 was identified as a protein partner of the von Hippel-Lindau tumor
      suppressor pVHL. The interaction of Jade-1 and pVHL correlates with renal cancer
      risk. We have investigated the molecular function of Jade-1. Jade-1 has two zinc
      finger motifs called plant homeodomains (PHD). A line of evidence suggests that
      the PHD finger functions in chromatin remodeling and protein-protein
      interactions. We determined the cellular localization of Jade-1 and examined
      whether Jade-1 might have transcriptional and histone acetyltransferase (HAT)
      functions. Biochemical cell fractionation studies as well as confocal images of
      cells immunostained with a specific Jade-1 antibody revealed that endogenous Jade
      1 is localized predominantly in the cell nucleus. Tethering of Gal4-Jade-1 fusion
      protein to Gal4-responsive promoters in co-transfection experiments activated
      transcription 5-6-fold, indicating that Jade-1 is a possible transcriptional
      activator. It was remarkable that overexpression of Jade-1 in cultured cells
      specifically increased levels of endogenous acetylated histone H4, but not
      histone H3, strongly suggesting that Jade-1 associates with HAT activity specific
      for histone H4. Deletion of the two PHD fingers completely abolished Jade-1
      transcriptional and HAT activities, indicating that these domains are
      indispensable for Jade-1 nuclear functions. In addition, we demonstrated that
      TIP60, a known HAT with histone H4/H2A specificity, physically associates with
      Jade-1 and is able to augment Jade-1 HAT function in live cells, strongly
      suggesting that TIP60 might mediate Jade-1 HAT activity. Thus, Jade-1 is a novel
      candidate transcriptional co-activator associated with HAT activity and may play
      a key role in the pathogenesis of renal cancer and von Hippel-Lindau disease.

PMID- 15502159
TI  - The stem cell pluripotency factor NANOG activates transcription with two
      unusually potent subdomains at its C terminus.
AB  - Embryonic stem cells are pluripotent progenitors for virtually all cell types in
      our body and thus possess unlimited therapeutic potentials for regenerative
      medicine. NANOG, an NK-2 type homeodomain gene, has been proposed to play a key
      role in maintaining stem cell pluripotency presumably by regulating the
      expression of genes critical to stem cell renewal and differentiation. Here, we
      provide the evidence that NANOG behaves as a transcription activator with two
      unusually strong activation domains embedded in its C terminus. First, we
      identified these two transactivators by employing the Gal4-DNA binding domain
      fusion and reporter system and named them WR and CD2. Whereas CD2 contains no
      obvious structural motif, the WR or Trp repeat contains 10 pentapeptide repeats
      starting with a Trp in each unit. Substitution of Trp with Ala in each repeat
      completely abolished its activity, whereas mutations at the conserved Ser, Gln,
      and Asn had relatively minor or no effect on WR activity. We then validated the
      activities of WR and CD2 in NANOG by constructing a reporter plasmid bearing five
      NANOG binding sites. Deletion of both WR and CD2 from NANOG completely eliminated
      its transactivation function. Paradoxically, whereas the removal of CD2 reduced
      NANOG activity by approximately 30-70%, the removal of WR not only did not
      diminish but actually enhanced its activity by approximately 50-100% depending on
      the cell lines analyzed. These data suggest that either WR or CD2 is sufficient
      for NANOG to function as a transactivator.

PMID- 15502160
TI  - Nuclear localization destabilizes the stress-regulated transcription factor Msn2.
AB  - The transcriptional program of yeast cells undergoes dramatic changes during the
      shift from fermentative growth to respiratory growth. A large part of this
      response is mediated by the stress responsive transcription factor Msn2. During
      glucose exhaustion, Msn2 is activated and concentrated in the nucleus.
      Simultaneously, Msn2 protein levels also drop significantly under this condition.
      Here we show that the decrease in Msn2 concentration is due to its increased
      degradation. Moreover, Msn2 levels are also reduced under chronic stress or low
      protein kinase A (PKA) activity, both conditions that cause a predominant nuclear
      localization of Msn2. Similar effects were found in msn5 mutant cells that block
      Msn2 nuclear export. To approximate the effect of low PKA activity on Msn2, we
      generated a mutant form with alanine substitutions in PKA phosphorylation sites.
      High expression of this Msn2 mutant is detrimental for growth, suggesting that
      the increased degradation of nuclear Msn2 might be necessary to adapt cells to
      low PKA conditions after the diauxic shift or to allow growth under chronic
      stress conditions.

PMID- 15502161
TI  - A conserved interaction between the replicative clamp loader and DNA ligase in
      eukaryotes: implications for Okazaki fragment joining.
AB  - The recruitment of DNA ligase I to replication foci and the efficient joining of
      Okazaki fragments is dependent on the interaction between DNA ligase I and
      proliferating cell nuclear antigen (PCNA). Although the PCNA sliding clamp
      tethers DNA ligase I to nicked duplex DNA circles, the interaction does not
      enhance DNA joining. This suggests that other factors may be involved in the
      joining of Okazaki fragments. In this study, we describe an association between
      replication factor C (RFC), the clamp loader, and DNA ligase I in human cell
      extracts. Subsequently, we demonstrate that there is a direct physical
      interaction between these proteins that involves both the N- and C-terminal
      domains of DNA ligase I, the N terminus of the large RFC subunit p140, and the
      p36 and p38 subunits of RFC. Although RFC inhibited DNA joining by DNA ligase I,
      the addition of PCNA alleviated inhibition by RFC. Notably, the effect of PCNA on
      ligation was dependent on the PCNA-binding site of DNA ligase I. Together, these
      results provide a molecular explanation for the key in vivo role of the DNA
      ligase I/PCNA interaction and suggest that the joining of Okazaki fragments is
      coordinated by pairwise interactions among RFC, PCNA, and DNA ligase I.

PMID- 15502162
TI  - Structural insights into the mechanism of formation of cellulosomes probed by
      small angle X-ray scattering.
AB  - Exploring the mechanism by which the multiprotein complexes of cellulolytic
      organisms, the cellulosomes, attain their exceptional synergy is a challenge for
      biologists. We have studied the solution structures of the Clostridium
      cellulolyticum cellulosomal enzyme Cel48F in the free and complexed states with
      cohesins from Clostridium thermocellum and Clostridium cellulolyticum by small
      angle x-ray scattering in order to investigate the conformational events likely
      to occur upon complexation. The solution structure of the free cellulase
      indicates that the dockerin module is folded, whereas the linker connecting the
      catalytic module to the dockerin is extended and flexible. Remarkably, the
      docking of the different cohesins onto Cel48F leads to a pleating of the linker.
      The global structure determined here allowed modeling of the atomic structure of
      the C. cellulolyticum dockerin-cohesin interface, highlighting the local
      differences between both organisms responsible for the species specificity.

PMID- 15502163
TI  - Comparative proteome analysis of Saccharomyces cerevisiae grown in chemostat
      cultures limited for glucose or ethanol.
AB  - The use of chemostat culturing enables investigation of steady-state
      physiological characteristics and adaptations to nutrient-limited growth, while
      all other relevant growth conditions are kept constant. We examined and compared
      the proteomic response of wild-type Saccharomyces cerevisiae CEN.PK113-7D to
      growth in aerobic chemostat cultures limited for carbon sources being either
      glucose or ethanol. To obtain a global overview of changes in the proteome, we
      performed triplicate analyses using two-dimensional gel electrophoresis and
      identified proteins of interest using MS. Relative quantities of about 400
      proteins were obtained and analyzed statistically to determine which protein
      steady-state expression levels changed significantly under glucose- or ethanol
      limited conditions. Interestingly, only enzymes involved in central carbon
      metabolism showed a significant change in steady-state expression, whereas
      expression was only detected in one of both carbon source-limiting conditions for
      15 of these enzymes. Side effects that were previously reported for batch
      cultivation conditions, such as responses to continuous variation of specific
      growth rate, to carbon-catabolite repression, and to accumulation of toxic
      substrates, were not observed. Moreover, by comparing our proteome data with
      corresponding mRNA data, we were able to unravel which processes in the central
      carbon metabolism were regulated at the level of the proteome, and which
      processes at the level of transcriptome. Importantly, we show here that the
      combined approach of chemostat cultivation and comprehensive proteome analysis
      allowed us to study the primary effect of single limiting conditions on the yeast
      proteome.

PMID- 15502164
TI  - Primary mouse keratinocyte culture.
AB  - Mouse epidermal keratinocytes have traditionally been difficult to grow in vitro.
      In this chapter, we present a method for isolating epidermal keratinocytes from a
      single, newborn mouse pup for long-term culture. The protocols we describe will
      be especially useful for the isolation and analysis of cells harvested from
      transgenic or knockout mice. We explain how to use a supplemented fibroblast
      conditioned medium, along with mouse collagen IV-coated culture dishes, to
      establish and subculture these fastidious cells for multiple passages. We
      describe how to induce expression of markers of the late stages of epidermal
      differentiation in cultured cells and how to ship whole mouse skins for culture
      at a site removed from the mice, should it be required. This chapter also
      contains a method of cryopreservation that ensures high cell viability after
      periods of storage over liquid nitrogen. The techniques described here in detail
      should be of interest to investigators currently producing transgenic or null
      mice with epidermal defects.

PMID- 15502165
TI  - Serial cultivation of primary adult murine keratinocytes.
AB  - In vitro cell culture is a necessary prerequisite in acquiring a thorough
      understanding of the biology and behavior of the cells of interest and is a
      critical first step in developing cellular therapies. Somatic stem cell biology
      is concerned with stem cells of the adult and how they may be utilized in
      regenerating tissue and ameliorating disease. Moreover, the incidence of disease
      increases with age, hence the demand for therapeutics is greatest among mature
      individuals. Therefore, an ability to grow and manipulate primary adult
      epithelial keratinocytes in vitro is of paramount importance in gaining insights
      into the biology of skin that may have clinical implications. A methodology has
      been developed that will enable investigators to isolate and serially culture
      adult basal keratinocytes from the epidermis of the mouse in a supplemented
      culture medium that selects for epithelial lineages and enhances their
      proliferation while inhibiting differentiation through many passages.

PMID- 15502166
TI  - Keratinocyte culture in the absence of substrate attachment.
AB  - This chapter deals with experimental protocols and considerations related to the
      culture of epithelial cells under anchorage-independent conditions in liquid
      media. This technique has proven to be a powerful tool in studying the effects of
      loss of extracellular matrix interaction on crucial aspects of epithelial cell
      biology. Specifically, examining cells in the absence of substrate attachment, as
      described in this chapter, will allow the investigator to study the effect of
      growth factors independently of cell adhesion. Several methods are discussed
      relating to the preparation of tissue culture plates for suspension cultures and
      to the choice of a suitable cell culture medium.

PMID- 15502167
TI  - Application of genetically modified feeder cells for culture of keratinocytes.
AB  - In living bodies, there are many cell-cell interactions, including epithelial
      mesenchymal interactions, to control cell growth and differentiation, and
      disturbances to such systems are believed to be a critical reason for many
      diseases, including cancer. Recently, many growth factors mediating epithelial-
      mesenchymal interactions have been revealed by molecular biological research.
      These growth factors are critical tools for both basic research and medical
      applications. However, obtaining purified forms of such growth factor proteins is
      difficult. To conveniently analyze the biological effects of such factors on
      keratinocytes, in this protocol, we describe how to introduce ectopic genes of
      growth factors of interest (sonic hedgehog and wnt-3 genes as examples) into
      Swiss-3T3 cells, one of the most widely used feeder cells for epithelial cell
      culture, and how to coculture the keratinocytes with them.

PMID- 15502168
TI  - Organ culture of developing mouse skin and its application for molecular
      mechanistic studies of morphogenesis.
AB  - In this chapter, we describe an organ culture method that allows skin tissues
      isolated from 12.5- or 13.5-d postcoitus mouse embryos to develop in a manner
      histologically and temporally similar to the process in vivo. In this culture
      system, epidermal growth factor specifically and completely inhibited the hair
      follicle formation with marginal effects on interfollicular epidermis. Using an
      adenovirus vector, one can transduce a gene into the epidermal and dermal cell
      layers without appreciable toxicity.

PMID- 15502169
TI  - Experimental models to analyze differentiation functions of cultured
      keratinocytes in vitro and in vivo.
AB  - In this chapter, we present technical details for the generation of in vitro skin
      equivalents consisting of collagen gels with incorporated fibroblasts covered by
      proliferating and differentiating keratinocytes. Epithelial-mesenchymal
      interactions are clearly manifest in these skin equivalents. Therefore, they have
      proven to be suitable experimental tools for a broad range of applications, e.g.,
      for studies on the the paracrine regulation of keratinocyte differentiation and
      proliferation. On the other hand, in vivo assays cannot be abandoned totally, in
      particular, when such properties as malignant growth potential, disturbed
      differentiation control in carcinogenesis, and impact on angiogenesis are
      concerned. For that reason, we additionally describe xenotransplantation
      techniques to graft human keratinocytes and skin equivalents, respectively, onto
      the dorsal muscle fascia of thymus-aplastic mice.

PMID- 15502170
TI  - In vitro fabrication of engineered human skin.
AB  - In vitro fabrication of human epidermal tissues that mimic the biochemical and
      morphologic properties of human skin, known as skin-equivalent (organotypic)
      cultures, has opened new avenues in the study of skin biology. In this chapter,
      methods for the generation of these tissues from their component parts are
      described. Conditions for culture of human keratinocytes and fibroblasts that
      allow optimal growth in skin equivalent cultures are delineated. These cell types
      are then sequentially combined so that keratinocytes are grown at an air-liquid
      interface on a contracted collagen gel containing dermal fibroblasts. The methods
      described enable the generation of human epidermal tissues that show in vivo-like
      tissue architecture and phenotype.

PMID- 15502171
TI  - In vivo labeling and analysis of epidermal stem cells.
AB  - To identify slowly cycling (label-retaining) keratinocytes in the cutaneous
      epithelium of mice, newborn female pups were injected with [3H]-thymidine twice
      daily for 3 d beginning the third day after birth. At 8-10 wk of age, skin from
      the dorsal side of the mice was removed and fixed. The skin was processed for
      paraffin embedding, and serial sections were prepared. Dewaxed and ethanol
      treated slides were dried and dipped into autoradiographic emulsion and allowed
      to dry in light tight box for 4 wk at 4 degrees C. After fixation with
      photographic fixer, the slides were washed, lightly stained, and viewed with a
      light microscope to observe and quantify cells that retained the labeling. Label
      retaining cells were identified by the black silver grains over their nuclei.

PMID- 15502172
TI  - Method for the harvest and assay of in vitro clonogenic keratinocytes stem cells
      from mice.
AB  - Primary adult mouse keratinocytes are harvested from the dorsal section of 6- to
      8-wk-old mice. Euthanized mice are clipped and sterilized with serial washes in
      provodine iodine and ethanol solutions. The skin of the mice is removed and
      treated with trypsin to detach the dermis from the epidermis. Cells harvested
      from this proven method can be used for molecular biology, biochemistry, or a
      variety of cell culture techniques, including the clonogenic cell assay presented
      here.

PMID- 15502173
TI  - FACS enrichment of human keratinocyte stem cells.
AB  - Recent work from our laboratory has led to the development and validation of
      fluorescence-activated cell sorting (FACS)-based techniques to prospectively
      isolate viable keratinocyte stem cells from both human and murine skin. Here we
      describe a step-by-step method to apply our technique to isolate epidermal
      keratinocytes from skin tissue, process them for immunofluorescent staining for
      cell surface markers, and subject them to fluorescence-activated cell sorting to
      obtain the stem, transient amplifying, and early differentiating keratinocyte
      fractions. These viable cells can then be placed into culture for further
      analysis or directly into keratinocyte assays, such as organotypic cultures or in
      vivo transplantation. This method will be useful for the complete biological
      characterization of keratinocyte progenitors with respect to wound healing,
      carcinogenesis, and therapeutic manipulation.

PMID- 15502174
TI  - Isolation, characterization, and culture of epithelial stem cells.
AB  - It is well accepted that homeostasis of continuously renewing adult tissues, such
      as the epidermis, is maintained by somatic stem cells. These are
      undifferentiated, self-renewing cells, which also produce daughter transit
      amplifying (TA) cells that make up the majority of the proliferative cell
      population in the tissues. Although still proliferative in nature, it is thought
      that TA cells can undergo only a finite number of cell divisions before they
      commit to leave the proliferative compartment and move toward terminal
      differentiation. Stem cells, on the other hand, have been assumed to persist
      throughout the lifetime of the organism. We directly demonstrated the presence of
      putative stem cells in the proliferative compartment of murine epithelia in 1981
      when we identified a small population of label-retaining cells (LRCs) in mouse
      stratified squamous epithelia. Since then, we have developed the method described
      here to isolate this population of epidermal stem cells (EpiSC). We showed that
      EpiSC are all keratin 14+ and thus of keratinocyte origin and not of mesenchymal
      or hematopoietic origin. We have also demonstrated that EpiSC can regenerate the
      epidermis, that they can permanently express a recombinant gene in the
      regenerated tissue, and that while the majority of EpiSC reside in the G1 phase
      of the cell cycle, they are not held out of the cell cycle, that they express
      proliferating genes and the mitotic cyclin B1 protein. Recently, we have shown
      that EpiSC have the capacity to alter their cell fate in vivo if placed into
      stress environments, i.e. after irradiation or wounding or when injected into a
      developing blastocyst environment. Thus being able to isolate EpiSC is critical
      for testing their use in cell and gene therapy.

PMID- 15502175
TI  - Keratin 19 as a stem cell marker in vivo and in vitro.
AB  - The skin is a dynamic tissue in which terminally differentiated keratinocytes are
      replaced by the proliferation of new epithelial cells that will undergo
      differentiation. The rapid and continual turnover of skin throughout life depends
      on a cell population with unique characteristics: the stem cells. These cells are
      relatively undifferentiated, retain a high capacity for self-renewal throughout
      their lifetime, have a large proliferative potential, and are normally slow
      cycling. The long-term regeneration of grafted cultured epidermis indicates that
      epidermal stem cells are maintained in cultures. In animals they can be
      identified with 3H-thymidine or bromodeoxyuridine based on their property of slow
      cycling. The development of markers such as keratin 19 also permits their study
      in human tissues. In this chapter, protocols to study skin stem cells using their
      property of slow cycling and their expression of keratin 19 will be described in
      detail. The methods include the double labeling of tissues for keratin 19 and
      label-retaining cells (auto radiography of 3H-thymidine) in situ. The labeling of
      keratin 19 by immunofluorescence of by flow cytometry is described for cells in
      vitro.

PMID- 15502176
TI  - Immunolocalization in the epidermis.
AB  - Immunohistochemistry is an efficient means of localizing specific proteins to
      their relative expression compartment in the epidermis thereby providing evidence
      as to their functionality. This chapter therefore describes a dependable method
      for immunolocalization within the epidermis.

PMID- 15502177
TI  - Epidermal cell analysis by RT-PCR.
AB  - Reverse transcription polymerase chain reaction is used for the semiquantitative
      analysis of epidermal gene expression, particularly when immunolocalization is
      not feasible because of the lack of antibodies available for novel genes. This
      chapter is therefore devoted to the delineation of a reliable reverse
      transcription polymerase chain reaction method to analyze gene expression both in
      vivo and in vitro.

PMID- 15502178
TI  - Whole-mount assays for gene induction and barrier formation in the developing
      epidermis.
AB  - The skin as a surface organ is uniquely accessible for whole embryo/fetal
      analyzes of developmental changes, such as gene induction, protein expression,
      formation of epidermal-derived appendages such as hair follicles, and formation
      of the protective barrier. Such analyses have emphasized the heterogenous nature
      of skin development, perhaps not surprising because epidermal development is
      programmed by heterogenous underlying mesenchyme. It is necessary to account for
      this heterogeneity by precisely matching body sites when correlating sequential
      events during development, for example, the activation of gene expression. In
      this chapter, protocols designed to assay whole-mount in situ hybridization and
      whole-mount barrier formation are presented. Formation of the protective barrier
      is the endpoint of epidermal terminal differentiation and defects in this process
      are reflected in failure, acceleration, or delay in barrier formation. Hence,
      these latter assays are of particular value as a rapid initial assay for
      epidermal developmental defects in genetically modified organisms.

PMID- 15502179
TI  - Analysis of early epidermal development in zebrafish.
AB  - The zebrafish (Danio rerio) is a member of the teleost (bony fish) lineage that
      diverged from the mammalian lineage 420 million years ago. Despite this ancient
      divergence, there are important similarities between the epidermis of fish and
      mammals. In addition, recent work suggests that the genes required for epidermal
      development in the zebrafish also are essential for this process in higher
      vertebrates, indicating that analysis of the zebrafish system will contribute to
      understanding mouse and human development. The zebrafish is a very useful genetic
      system, and many mutants with epidermal defects have been obtained in large-scale
      genetic screens. In addition, zebrafish embryos are transparent, develop
      externally, and can be collected in abundance. The aim of this chapter is to
      provide the researcher with basic protocols to examine gene expression, cell
      proliferation, and cell death in the developing zebrafish. Although only a few
      specific epidermal markers have been identified in the zebrafish thus far, we
      also provide a list of useful genes for epidermal analysis.

PMID- 15502180
TI  - Analysis of E2F factors during epidermal differentiation.
AB  - The multigene E2F family of transcription factors is central in the control of
      cell cycle progression. The expression and activity of E2F proteins is tightly
      regulated transcriptionally and posttranslationally as a function of the
      proliferation and differentiation status of the cell. In this chapter, we review
      protocols designed to determine E2F mRNA abundance in tissues by in situ
      hybridization techniques. The ability to culture primary epidermal keratinocytes
      and maintain them as either undifferentiated or terminally differentiated cells
      allows the biochemical and molecular characterization of changes in E2F
      expression and activity. Thus, we also discuss in detail methods to analyze E2F
      protein abundance by immunoblot and their ability to bind DNA in cultured cells
      using electrophoretic mobility shift assays.

PMID- 15502181
TI  - Analysis of HOX homeodomain proteins and gene transcripts in the epidermis.
AB  - HOX homeodomain proteins are thought to be master developmental regulators of
      tissue patterning during embryogenesis. These DNA binding proteins also have
      diverse roles in adult cell function, and derangement of HOX genes has been
      associated with several types of cancer. In this chapter we present protocols for
      the immunohistochemical localization of HOX proteins in the epidermis. We also
      provide in situ hybridization protocols for detection of HOX gene mRNA
      transcripts in the epidermis.

PMID- 15502182
TI  - Apoptosis in the epidermis.
AB  - Keratinization is a specialized form of apoptosis that produces the stratum
      corneum concomitant with keratinocyte cell death. Apoptosis of keratinocytes
      occurs not only during normal keratinization but also in response to various
      intracellular or extracellular death stimuli, such as genetic defects or UVB. In
      general, apoptosis is characterized by chromatin condensation, membrane blebbing,
      cell shrinkage, formation of apoptotic bodies, and deoxyribonucleic acid
      fragmentation. The nick-end labeling technique is a method to detect DNA
      fragmentation and is useful to assess the presence of apoptotic cells in tissues
      or cells. In this chapter, a practical procedure for nick-end labeling using
      paraffin-embedded sections of skin specimens is described.

PMID- 15502183
TI  - Fate of desmosomal proteins in apoptotic epidermal cells.
AB  - In epidermal cells desmosomes represent major sites of basolateral cell-cell
      contacts that play an important role for epidermal homeostasis. Excess or damaged
      cells are often removed by apoptosis. To release apoptotic cells from the tissue,
      intercellular contacts have to be broken. Here detailed protocols to analyze
      desmosomal proteins in apoptotic cells are described.

PMID- 15502184
TI  - Analysis of connexin 43 expression on keratinocytes using flow cytometry.
AB  - Single-cell suspensions of primary keratinocytes comprise a heterogeneous cell
      population that consists of basal cells (stem cells, transient amplifying cells,
      and post-mitotic basal cells) and suprabasal cells at different stages of
      differentiation. Quantitative data for the differential expression of epitopes on
      single cells can be obtained using a flow cytometer. Simultaneous analysis of two
      intracellular epitopes, keratin 14 and connexin 43, using flow cytometry after
      keratinocyte isolation, fixation, permeabilization, and fluorescent
      immunolabeling is described. Three subsets of cells could be distinguished: stem
      cells (basal cells [keratin 14 positive] that lack connexin 43 expression);
      suprabasal cells (connexin 43-positive, keratin 14-negative cells); and basal
      cells (keratin 14 positive) that express connexin 43. The last population of
      keratinocytes includes both transient amplifying cells and postmitotic basal
      cells. The scatter characteristics of each cell population are also described.

PMID- 15502185
TI  - MMP-9 and TIMP-1 assays in keratinocyte cultures.
AB  - Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases
      (TIMPs) are known to play important roles in the metabolism of epidermal tissue.
      Among them, MMP-9 and its relatively specific inhibitor, TIMP-1, have been
      reported to be involved in a variety of pathophysiological conditions. To detect
      MMP-9 and TIMP-1 in conditioned medium from keratinocytes in culture, I describe
      methods of gelatin-zymography and reverse zymography (which are used both
      qualitatively and quantitatively) and of Western blotting analysis using
      antibodies specific for each molecule. These methods are useful tools for
      elucidating the pathophysiology of skin conditions and for seeking new drugs.

PMID- 15502186
TI  - Characterization of epithelial cells in the hair follicle with S100 proteins.
AB  - S100 proteins are the largest subgroup of Ca2+ binding proteins with the EF-hand
      structural motif. A unique feature of this protein family is that individual
      members are localized in specific cellular compartments. For example, various
      S100 proteins are expressed in very restricted regions of the hair follicle:
      S100A3 and S100A6 in distinct postmitotic differentiated epithelial cells and
      S100A4 and S100A6 in the epithelial stem cell compartments. Characterization of
      epithelial cells by their S100 protein expression profiles is therefore useful
      for a better understanding of the dynamic cellular events associated with hair
      follicle development and regeneration. This chapter presents our protocols for
      probe preparations and histochemical analyses of S100 proteins in hair follicle
      tissue, including simultaneous detection procedures for pulse-labeled
      proliferating cells.

PMID- 15502187
TI  - Immunoelectron microscopic analysis of cornified cell envelopes and antigen
      retrieval.
AB  - In this chapter, postembedding immunoelectron microscopy methods for studies of
      cornified cell envelopes are provided. Human epidermal tissue samples are used as
      the material. The samples are cryo-fixed without chemical fixation, freeze
      substituted at a low temperature, and embedded in Lowicryl K11M resin. For
      immunostaining, colloidal gold-conjugated secondary antibodies are used. Methods
      for retrieval of masked epitopes are also described.

PMID- 15502188
TI  - Cell kinetic analysis in artificial skin using immunochemical methods.
AB  - Cell kinetic studies provide important information on histogenesis in vivo and in
      vitro. In this regard, specific antibodies to cell cycle-related antigens have
      been raised and characterized, thus permitting the study of cell kinetics using
      immunochemical methods. Recent advances in culture technology permitted the
      generation of human skin equivalents in vitro. We here provide detailed practical
      procedures for the study of epidermal cell kinetics in a model of artificial skin
      using immunohistochemistry and flow cytometry. The combined application of both
      techniques allows a precise detection of tissue growth sites and a quantitative
      assessment of cell growth. Moreover, simultaneous analysis of differentiation
      markers and proliferation antigens may be useful to understand molecular
      mechanisms that regulate tissue growth and development.

PMID- 15502189
TI  - Proliferation, differentiation, and inflammation in normal and hyperproliferative
      skin using multiparameter flow cytometry.
AB  - Our knowledge of the etiology and pathogenesis of skin diseases characterized by
      abnormal growth is relatively limited. Even more important, still very little is
      known of how epidermopoeisis is controlled in normal epidermis. There is no cure
      for skin diseases caused by abnormal growth control, such as psoriasis.
      Mechanisms are complex, additional models for epidermal growth and
      differentiation, and specific techniques to analyze these processes, are needed.
      Therefore, we have developed flow cytometric techniques to study epidermal growth
      over the past two decades. A prerequisite for accurate and reliable flow
      cytometric analysis is a high quality of epidermal single-cell suspensions. In
      this chapter, protocols are described for preparation of single-cell suspensions
      and protocols for the multiparameter flow cytometric analysis of growth behavior
      in normal and hyperproliferative epidermis.

PMID- 15502190
TI  - Fluorimetric DNA assay of cell number.
AB  - This fluorimetric assay has utility for the accurate assessment of cultured
      epidermal cell numbers by virtue of their deoxyribonucleic acid content, which is
      the most significant correlate available. The improvement in fluorochromes in the
      recent past makes PicoGreen the dye of choice for this, with its greatly
      increased sensitivity (+/- 50 cells) over the Hoechst and DAPI stains and which
      remains linear over several orders of magnitude with a single dye concentration.
      The assay involves minimal liquid handling to achieve cell disruption by sodium
      dodecyl sulfate in saline sodium citrate buffer, and PicoGreen staining is
      rapidly assayed by a multiwell plate reading fluorimeter, which can be automated
      for robotic high throughput use. Highly fibrous cells like epidermal
      keratinocytes can be disrupted using 8 M urea and assayed after dilution. The
      assay is also compatible with tritiated thymidine incorporation.

PMID- 15502191
TI  - Keratinocyte transient transfections.
AB  - The goal of this chapter is to give the reader a concise and easy-to-follow guide
      to proven transient transfection techniques for primary strains and continuous
      lines of keratinocytes. The emphasis is on readily available and inexpensive
      resources that also allow for repeatability and adaptability to scale,
      experimental conditions, and sample replicates. In addition, basic cell culture
      techniques necessary to achieve optimal transfection results are provided.
      Although specified for keratinocytes, these techniques also work well for simple
      epithelial lines and common laboratory lines, such as COS-7 and CV-1. The
      standard precipitation protocol is suitable for many experimental designs, and
      the poly-L-ornithine protocol is intended for situations where calcium is
      contraindicated. The extended notes section provides necessary technical details
      to guide the novice user and reminders to the experienced scientist that success
      with the protocol will depend on several quantitative and qualitative factors
      including promoter strength, cell culture practices and plasmid isolation.

PMID- 15502192
TI  - Tetracycline-regulated gene expression in epidermal keratinocytes.
AB  - The tetracycline-regulated expression system developed by Gossen and Bujard is a
      powerful genetic tool that permits the expression of any gene construct
      introduced into either cultured cells or transgenic animals to be precisely
      controlled. It involves two components, a regulatory component based on the
      prokaryotic tetracycline repressor (TetR) and a response plasmid that expresses
      the gene of interest under control of the tetracycline-response element. In this
      paper, we review the Tet system methodology, discuss the available vector
      systems, and describe how to prepare and characterize keratinocyte cell lines
      that express a gene under tetracycline control. The methodology involves the
      development of stable cell lines expressing the TetR protein (either tTA or rtTA,
      expressed as a fusion with the VP16 activation domain), and a second set of
      double-stable cell lines that contain both TetR and the response plasmid
      (tetracycline-response element-gene X) expressed under tetracycline control. As
      an example of this methodology, we discuss our recently developed keratinocyte
      cell lines that express human filaggrin in a tetracycline- regulated manner. This
      technique, now also available in retrovirus and adenovirus-based vectors, is
      applicable both to the study of genes that are toxic to cells and more generally
      to understand how genes regulate cell structure/function, growth, and
      differentiation.

PMID- 15502193
TI  - Gene targeting by oligonucleotides in keratinocytes.
AB  - Oligonucleotide-directed gene alteration produces a targeted deoxyribonucleic
      acid (DNA) sequence change in the genome of mammalian cells at low frequency that
      is only detectable by highly sensitive methods. To measure the low frequency, we
      have established an assay using the mutant lacZ vector that contains a single
      point mutation in the lacZ gene, which results in a loss of enzymatic activity.
      When cells containing this mutant reporter gene are corrected by gene targeting,
      the mutant beta-galactosidase enzymatic activity is restored, and corrected cells
      can be visualized by histochemical staining. Using this method, we detected a low
      level of gene correction in the primary human keratinocytes, in spite of highly
      efficient nuclear uptake of oligonucleotide. Therefore, it is important to
      consider many other factors for successful gene repair, including DNA repair and
      recombination activities, status of replication and transcription, in addition to
      the well-known requirements like the quality and delivery of oligodeoxy
      nucleotides to cells. Available methods to manipulate epidermal stem cells and
      the accessibility of the tissue make the epidermis attractive for gene targeting.
      Given the low frequency, however, general selection procedures and amplification
      of corrected cells via epidermal stem cells are ultimately needed to make the
      gene repair technology practical.

PMID- 15502194
TI  - Promoter analysis in the human SPRR gene family.
AB  - Protocols to study the regulation of a conserved multigene family (SPRR genes)
      during calcium-induced differentiation of cultured normal human keratinocytes
      (NHKs) are provided. Transfection of promoter-reporter (CAT or luciferase)
      constructs, combined with promoter truncation, can be used to study the
      expression of individual SPRR genes and to identify specific transcription factor
      binding sites. Interaction of regulatory factors with these control elements can
      be visualized and quantified by electro phoretic mobility shift analysis.
      Inclusion of specific antibodies in these experiments will identify the
      transcription factors involved in the observed mobility shift (supershift). A
      competitive electrophoretic mobility shift analysis, that is well suited to study
      the differential regulation of various SPRR members, is also described. These
      methods should be applicable to the study of other multigene families regulated
      during keratinocyte terminal differentiation.

PMID- 15502195
TI  - Stable integration of large PAC constructs in keratinocytes.
AB  - Transfer of P1-derived artificial chromosome (PAC) deoxyribonucleic acid (DNA)
      into keratinocytes is an extremely important technique that enables functional
      studies of keratinocyte-specific genes to be performed and genomic gene therapy
      for inherited and acquired diseases to be attempted. Ex vivo gene therapy
      approaches are possible using well-established conditions for keratinocyte
      culture and grafting, whilst the skin is the most accessible organ for
      administering in vivo therapy. PAC vectors lack relevant reporter genes to
      distinguish transfected mammalian cells from the non-transfected background, or
      to select clones in which the PAC construct has stably integrated into the
      genome. In this chapter, protocols to retrofit a reporter gene cassette will be
      described, together with techniques for transfecting large PAC constructs into
      keratinocytes without breakage. Protocols to select for stable integrants and to
      assess the integration event(s) within the keratinocyte genome will also be
      provided.

PMID- 15502196
TI  - Targeted somatic mutagenesis in the mouse epidermis.
AB  - The efficient introduction of somatic mutations in a given gene at a given time
      and in specific cell types of the skin will greatly facilitate the studies of a
      number of genes expressed in the skin and the production of animal models for
      skin diseases. We describe here strategies and techniques to create
      spatiotemporally controlled somatic mutations of target genes in the skin using a
      conditional Cre/LoxP system. They are based on cell-specific expression of the
      chimeric Cre recombinase Cre-ERT2, whose activity is induced by antiestrogens
      such as Tamoxifen (Tam), and which is obtained by fusing the Cre recombinase with
      a mutated ligand binding domain of the human estrogen receptor ERalpha. As an
      example, we present ablation of the retinoid receptor RXRalpha in epidermal basal
      keratinocytes of adult mice.

PMID- 15502197
TI  - Methods to study protein-protein interactions.
AB  - Protein-protein interactions are the underpinnings of a vast number of cellular
      processes. In recent years, the convergence of biochemistry, cellular, and
      molecular biology has made available a number of powerful techniques for studying
      such interactions. These techniques vary in their sensitivity, efficiency, and
      rapidity, but judicial deployment of a combination of them has proved to be
      effective and reliable. Here, we highlight a version of the yeast two-hybrid
      assay originally pioneered by Fields and Song (1989) and subsequently
      enhancements by other investigators. We also briefly describe a number of new
      fluorescent imaging-based biophysical techniques for studying protein-protein
      interactions FRET, FCS, and BiFC. Together, these constitute an impressive
      collection of tools for studying interactions among proteins.

PMID- 15502198
TI  - Isolation of recombinant phage-displayed antibodies recognizing skin
      keratinocytes.
AB  - Advances in our understanding of biology at the molecular level are very much
      driven by improvements in the scientist's tool box. Such improvements may not
      only be an introduction of new techniques like polymerase chain reaction, but as
      much an increment of for example the sensitivity of existing methods. The in
      vitro generation of antibodies using phage display is one such technique, which
      continuously has been developed since its introduction more than 10 yr ago. As a
      result, selection of phage-displayed antibodies is emerging as a proteomic tool
      for the identification of differentially expressed cell surface antigens. Here, a
      method is described that enables the rapid isolation of a panel of recombinant
      antibodies recognizing epidermal skin keratinocytes. The method exploits the
      properties of a protease sensitive helper phage and facilitates the isolation of
      affinity-binders after a single round of selection. This assures a high diversity
      of binders owing to the reduction of experimental noise.

PMID- 15502199
TI  - Analysis of tissue-specific DNA methylation during development.
AB  - The establishment of a cell identification method more accurate than the
      conventional morphological and cell-type-specific marker analyses has been
      desired. DNA methylation is related to the gene activity including gene-silencing
      and is a key mechanism of epigenetics underling cellular differentiaion and
      development in mammals. Recent studies indicated that there exist unique genomic
      DNA methylation profiles specific to the cell type. DNA methylation profiles a
      mechanism for memorizing the set of genes inherent in individual type of cells.
      In this chapter, we present the methods to analyze DNA methylation status for
      identifying cells or tissues.

PMID- 15502200
TI  - Serial analysis of gene expression in human keratinocytes and epidermis.
AB  - The demand for large-scale gene expression analysis tools is on the rise now that
      several genomes have been sequenced. One of these tools, serial analysis of gene
      expression (SAGE), allows the qualitative as well as quantitative analysis of a
      large number of genes in a defined tissue or culture model. SAGE has already been
      successfully used to identify differentially expressed genes in normal
      physiological processes and pathological conditions. This chapter focuses on the
      SAGE protocol and its application to cultured human keratinocytes, and on
      MicroSAGE, an adapted protocol that allows the use of small amounts of mRNA from
      isolated epidermis or a skin biopsy.

PMID- 15502201
TI  - Methods for gene expression profiling in dermatology research using DermArray
      nylon filter DNA microarrays.
AB  - Here we present methods of gene expression profiling using nylon filter
      deoxyribonucleic acid (DNA) microarrays and radiolabeled and nonradiolabeled
      hybridization probes. DermArray(R) nylon filter DNA microarrays were designed
      specifically for use in dermatology research. A patent-pending method was used to
      select approx 4400 highly informative, sequence-verified human cDNA clones for
      this DNA micro array. Using DermArray(R) filters, biomarkers have been discovered
      for normal and pathologic cells from skin, and for responses to dermatologic
      drugs. As an example, gene expression profiling was performed with hydroquinone
      treated SKMel-28 cells, a melanoma cell line. Also included are the methods for
      bioinformatic analysis using Pathwaystrade mark software.

PMID- 15502202
TI  - Two-photon fluorescence imaging and reactive oxygen species detection within the
      epidermis.
AB  - Two-photon fluorescence microscopy is used to detect ultraviolet-induced reactive
      oxygen species (ROS) in the epidermis and the dermis of ex vivo human skin and
      skin equivalents. Skin is incubated with the nonfluorescent ROS probe
      dihydrorhodamine, which reacts with ROS such as singlet oxygen and hydrogen
      peroxide to form fluorescent rhodamine-123. Unlike confocal microscopic methods,
      two-photon excitation provides depth penetration through the epidermis and dermis
      with little photodamage to the sample. This method also provides submicron
      spatial resolution such that subcellular areas that generate ROS can be detected.
      In addition, comparative studies can be made to determine the effect of applied
      agents (drugs, therapeutics) upon ROS levels at any layer or cellular region
      within the skin.

PMID- 15502203
TI  - In vivo transplantation of engineered human skin.
AB  - Tissue engineering approaches have enabled the development of methodologies that
      allow long-term, in vivo studies in epidermal biology. This has been accomplished
      through in vivo transplantation of human epidermal cells fabricated as three
      dimensional, skin-equivalents in vitro. The methodologies presented in this
      chapter describe how skin-equivalent (organotypic) cultures are transplanted to
      nude mice to generate human skin grafts that normalize their tissue architecture,
      basement membrane structure and barrier function shortly after grafting. By
      grafting skin equivalents as composite cultures featuring well-differentiated
      human epidermis and fibroblasts in collagen gel, transplants are "primed" for
      accelerated take of grafted tissues. The methods outlined can generate stable,
      human epidermis that mimics the in vivo tissue.

PMID- 15502204
TI  - Epidermis-targeted gene transfer using in vivo electroporation.
AB  - The skin is an important target for gene transfer because of its easy
      accessibility. Recently, we demonstrated that an in vivo electroporation approach
      could be applied to plasmid deoxyribonucleic acid delivery in rat skin of the
      abdominal area. Plate-and-fork type electrodes were effective for gene delivery
      by skin-targeted gene transfer. Eight 12-24 V, 50-m electric pulses were
      delivered through the electrodes. Skin injection with pCAGGS-lacZ showed lacZ
      gene expression in the upper most cell layers (horny, granular, and prickle cell
      layers) of the epidermis on day 1 and in the subcutaneous muscle layer on day 7
      after the pCAGGS-lacZ transfer. Slight skin damage as the result of the gene
      transfer procedure was evident on day 1 but absent by day 7. These results
      demonstrate that plasmid deoxyribonucleic acid transfer by in vivo electro
      poration at low voltage is a useful procedure for short-term skin-targeted gene
      transfer.

PMID- 15502205
TI  - Gene and stem cell therapy of the hair follicle.
AB  - The hair follicle is a highly complex appendage of the skin containing a
      multiplicity of cell types. The follicle undergoes constant cycling through the
      life of the organism including growth and resorption with growth dependent on
      specific stem cells. The targeting of the follicle by genes and stem cells to
      change its properties, in particular, the nature of the hair shaft is discussed.
      Hair follicle delivery systems are described such as liposomes and viral vectors
      for gene therapy. The nature of the hair follicle stem cells is discussed, in
      particular, its pluripotency.

PMID- 15502206
TI  - 32P-postlabeling analysis of DNA adducts.
AB  - 32P-Postlabeling analysis is an ultrasensitive method for the detection of DNA
      adducts, such as those formed directly by the covalent binding of carcinogens and
      mutagens to bases in DNA, as well as other DNA lesions resulting from
      modification of bases by endogenous or exogenous agents (e.g., oxidative damage).
      The procedure involves four main steps: enzymatic digestion of a DNA sample;
      enrichment of the adducts; radiolabeling of the adducts by T4 kinase-catalyzed
      transference of 32P-orthophosphate from [gamma-32P]ATP; and chromatographic
      separation of labeled adducts and detection and quantification by means of their
      radioactive decay. Using 10 microg or less of DNA, this technique is capable of
      detecting adduct levels as low as one adduct in 10(9)-10(10) normal nucleotides.
      It is applicable to a wide range of investigations, including monitoring human
      exposure to environmental or occupational carcinogens, determining whether a
      chemical has genotoxic properties, analysis of the genotoxicity of complex
      mixtures, elucidation of the activation pathways of carcinogens, and monitoring
      of DNA repair.

PMID- 15502207
TI  - Modification of the 32P-postlabeling method to detect a single adduct species as
      a single spot.
AB  - The original 32P-postlabeling method developed by Randerath and his colleagues
      has been modified to detect a single type of adduct as a single spot in thin
      layer chromatography (TLC), because some types of adducts gave multiple adduct
      spots by the original method. In the remodified methods, DNA is first digested
      with micrococcal nuclease and phophodiesterase II and then labeled with [gamma
      32P]ATP under standard or adduct-intensification conditions. Since the labeled
      digest includes adducted mono-, di-, and/or oligo-deoxynucleotides, it is further
      treated with phosphatase and phosphodiesterase prior to TLC. The labeled digest
      is treated with nuclease P1 (NP1) in method I, and with T4 polynucleotide kinase
      and NP1 in method II, and then with phosphodiesterase I in both cases, and
      subjected to TLC. The advantage of these methods is that the number of adduct
      species formed can be estimated by TLC.

PMID- 15502208
TI  - DNA isolation and sample preparation for quantification of adduct levels by
      accelerator mass spectrometry.
AB  - A protocol is described for the isolation of DNA and subsequent preparation of
      samples for the measurement of adduct levels by accelerator mass spectrometry
      (AMS). AMS is a highly sensitive technique used for the quantification of adducts
      following exposure to carbon-14- or tritium-labeled chemicals, with detection
      limits in the range of one adduct per 10(11)-10(12) nucleotides. However, special
      precautions must be taken to avoid cross-contamination of isotope between samples
      and to produce a sample that is compatible with AMS. The DNA isolation method
      described is based on digestion of tissue with proteinase K, followed by
      extraction of DNA using Qiagen DNA isolation columns. DNA is then precipitated
      with isopropanol, washed repeatedly with 70% ethanol to remove salt, and then
      dissolved in water. This method has been used to generate reliably good yields of
      uncontaminated, pure DNA from animal and human tissues for analysis of adduct
      levels. For quantification of adduct levels from 14C-labeled compounds, DNA
      samples are then converted to graphite, and the 14C content is measured by AMS.

PMID- 15502209
TI  - Fluoroimaging-based immunoassay of DNA photoproducts in ultraviolet-B-irradiated
      tadpoles.
AB  - Sensitive and accurate measurement of photoproducts induced in DNA by natural or
      artificial ultraviolet-B (UVB; and UVC) light is essential to evaluate the toxic
      and mutagenic effects of this radiation. Monoclonal antibodies specific for the
      two major classes of photoproducts-cyclobutane pyrimidine dimers (CPDs) and
      pyrimidine-[6-4]-pyrimidinone photoproducts ([6-4]PPs)-have made possible highly
      specific and sensitive assays. Described here is the use of these primary
      antibodies with fluorescent secondary antibodies to generate 96-spot arrays.
      Stable fluorescence signals are rapidly and sensitively scored by fluoroimaging
      and computer analysis of peak-and-valley traces. CPD levels in a series of
      calibration standards are determined by acid hydrolysis/thin-layer chromatography
      analyses of radiolabeled bacterial DNA, UV-irradiated to known high fluences, and
      linear extrapolation to known lower fluences. The nonlinear fluorescence vs CPD
      curve reflects the effect of photoproduct concentration on single vs double
      binding by divalent antibody proteins. This technique is applied to photoproducts
      in whole inbred Xenopus laevis tadpoles, chronically irradiated at a series of
      UVB fluences that reach a lethality threshold when in vivo steady-state
      photoproduct levels are still quite low. As few as 0.01-0.02 CPDs per DNA kbp can
      be reliably detected, at signal/noise ratios of roughly 3:1.

PMID- 15502210
TI  - Analysis of DNA strand cleavage at abasic sites.
AB  - Abasic sites in DNA arise under a variety of circumstances, including
      destabilization of bases through oxidative stress, as an intermediate in base
      excision repair, and through spontaneous loss. Their persistence can yield a
      blockade to RNA transcription and DNA synthesis and can be a source of mutations.
      Organisms have developed an enzymatic means of repairing abasic sites in DNA that
      generally involves a DNA repair pathway that is initiated by a repair protein
      creating a phosphodiester break ("nick") adjacent to the site of base loss. Here
      we describe a method for analyzing the manner in which repair endonucleases
      differ in the way they create nicks in DNA and how to distinguish between them
      using cellular crude extracts.

PMID- 15502211
TI  - Premature chromosome condensation in human resting peripheral blood lymphocytes
      for chromosome aberration analysis using specific whole-chromosome DNA
      hybridization probes.
AB  - This paper describes a unique, simple, and rapid method for inducing premature
      chromosome condensation (PCC) in "resting" human peripheral blood lymphocytes
      (HPBLs) and also explains an approach to studying numerical changes and/or
      structural aberrations involving specific chromosomes. HPBLs are isolated from
      whole blood on a density gradient and, to induce PCC, are incubated at 37 degrees
      C in cell culture medium supplemented with a phosphatase inhibitor (okadaic acid
      or calyculin A), adenosine triphosphate (ATP), and p34cdc2/cyclin B kinase (an
      essential component of mitosis-promoting factor [MPF]). PCC spreads are prepared
      on glass slides after a brief hypotonic treatment of cells and fixing in acetic
      acid/methanol fixative. Aberrations involving specific chromosomes are analyzed
      after in situ hybridization and chromosome painting by fluorescence microscopy.
      Normal (undamaged) cells display two fluorescent spots per chromosome, whereas
      aneuploid cells, or cells with a structural aberration involving the specific
      chromosome corresponding to the painting probe, may show more than two spots.
      This method may be used in many biological and toxicological fields that require
      analysis of numerical and structural aberrations involving specific chromosomes.

PMID- 15502212
TI  - Mutagen-induced chromatid breakage as a marker of cancer risk.
AB  - Risk assessment is now recognized as a multidisciplinary process, extending
      beyond the scope of traditional epidemiologic methodology to include biological
      evaluation of interindividual differences in carcinogenic susceptibility.
      Modulation of environmental exposures by host genetic factors may explain much of
      the observed interindividual variation in susceptibility to carcinogenesis. These
      genetic factors include, but are not limited to, carcinogen metabolism and DNA
      repair capacity. This chapter describes a standardized method for the functional
      assessment of mutagen sensitivity. This in vitro assay measures the frequency of
      mutagen-induced breaks in peripheral lymphocytes. Mutagen sensitivity assessed by
      this method has been shown to be a significant risk factor for tobacco-related
      malignancies, especially those of the upper aerodigestive tract. Mutagen
      sensitivity may therefore be a useful member of a panel of susceptibility markers
      for defining high-risk subgroups for chemoprevention trials. This chapter
      describes methods for and discusses results from studies of mutagen sensitivity
      as measured by quantifying chromatid breaks induced by chromosome breaking
      agents, such as the gamma-radiation radiomimetic DNA crosslinking agent bleomycin
      and chemicals that form so-called bulky DNA adducts, such as 4-NQO and the
      tobacco smoke constituent, benzo[a]pyrene, in short-term cultured peripheral
      blood lymphocytes.

PMID- 15502213
TI  - Flow cytometric analysis of micronuclei in erythrocytes.
AB  - The in vivo micronucleus (MN) test in bone marrow or peripheral blood
      erythrocytes is widely used as a short-term assay for the detection of agents
      able to induce chromosome aberrations in somatic cells and has also been shown to
      have good predictive potential for the identification of carcinogens and germ
      cell mutagens. The endpoint used is the scoring of micronuclei (MN) in bone
      marrow or peripheral blood erythrocytes of mice or rats. In this chapter, a
      detailed description of the flow cytometric micronucleus test will be given, as
      well as a more general description of the manual micronucleus assay. The DNA of
      MN is identified using the DNA-specific fluorescent stain Hoechst 33342;
      discrimination between polychromatic and normochromatic erthrocytes is based on
      staining with thiazole orange, a fluorescent probe with high RNA affinity. The
      use of flow-cytometric quantification of micronucleated polychromatic and
      normochromatic erythrocytes (MNPCE and MNNCE), beyond replacing manual
      enumeration, provides substantial advantages in terms of speed of analysis, as
      well as sensitivity. The general description of the MN assay briefly covers
      choice of animal species and strains, treatment regime, sampling times, and data
      interpretation. The description of the flow cytometric assay covers in detail
      erythrocyte preparation and purification, fixation, staining, data acquisition,
      and data analysis.

PMID- 15502214
TI  - The comet assay: a sensitive genotoxicity test for the detection of DNA damage.
AB  - The comet assay or single-cell gel (SCG) test is a microgel electrophoresis
      technique that measures DNA damage at the level of single cells. A small number
      of cells suspended in a thin agarose gel on a microscope slide is lysed,
      electrophoresed, and stained with a fluorescent DNA binding dye. Cells with
      increased DNA damage display increased migration of chromosomal DNA from the
      nucleus toward the anode, which resembles the shape of a comet. In its alkaline
      version, which is mainly used, DNA single-strand breaks, DNA double-strand
      breaks, alkali-labile sites, and single-strand breaks associated with incomplete
      excision repair sites cause increased DNA migration. On the other hand,
      crosslinks (DNA-DNA or DNA-protein) can lead to decreased DNA migration.
      Variations of the comet assay have been established for the detection of specific
      DNA base modifications. Here we describe the basic methodology of the alkaline
      comet assay, establishing a sensitive protocol for obtaining reproducible and
      reliable data. Applications of the comet assay for detecting DNA damage in
      individual cells are briefly reviewed.

PMID- 15502215
TI  - Computerized image analysis software for the comet assay.
AB  - Single-cell gel electrophoresis (SCGE) or the comet assay is a powerful tool for
      the detection of DNA single- and double-strand breaks and base damage and for
      investigating the kinetics of DNA strand break rejoining in human and animal
      model systems. It is a versatile technique that can be applied in various areas
      of biomedical research. This chapter highlights the importance of computerized
      analysis and data processing for the comet assay and describes the criteria used
      for manual evaluation of comets and their limitations compared with the computer
      based analysis. It describes in detail SCGE-Pro, a semiautomatic software
      developed in our laboratory for comet evaluation and data processing. For
      comparison, some of the commercially available software for analysis of data from
      the comet assay is also described.

PMID- 15502216
TI  - The comet-FISH technique: a tool for detection of specific DNA damage and repair.
AB  - The comet-FISH technique described in this protocol is a tool to detect genome
      region-specific DNA damage and repair. It is a combination of two established
      techniques, the comet assay (or single-cell gel electrophoresis, or the single
      cell gel test), to separate highly fragmented from moderately or nonfragmented
      DNA and to measure it, and fluorescence in situ hybridization (FISH), to
      specifically label DNA sequences of interest. Comet-FISH exists in two versions,
      based on the neutral and the alkaline comet assays. A detailed description of the
      comet assay is given in Chapter 9, so readers who are not familiar with this
      technique can work directly with the protocol described here, without referring
      to additional protocols reported elsewhere. The neutral version of the comet
      assay detects double-strand breaks, while the alkaline version detects both
      double- and single-strand breaks as well as abasic sites or sites of incomplete
      repair. This chapter also details cell preparation and production of the
      hybridization probes adapted to the comet-FISH technique. Finally, microscopic
      analysis of comet-FISH results is described, and possible procedures of
      quantification of the specific DNA damage are presented.

PMID- 15502217
TI  - DNA double-strand break damage and repair assessed by pulsed-field gel
      electrophoresis.
AB  - This assay quantifies the amount of DNA double-strand break (DSB) damage in
      attached cell populations embedded in agarose and assayed for migratory DNA using
      pulsed-field gel electrophoresis (PFGE) with ethidium bromide staining. The assay
      can measure pre-existing damage, as well as induction of DSB by chemical (e.g.,
      bleomycin), physical (e.g., X-irradiation), or biological (e.g., restriction
      enzymes) agents. By incubating the cells under physiological conditions prior to
      processing, the cells are allowed to repair DSB, primarily via the process of
      nonhomologous end joining. The amount of repair, corresponding to the repair
      capacity of the treated cells, is then quantified by determining the ratio of the
      fractions of activity released in these repaired lanes in comparison with the
      total amount of DNA fragmentation following determination of a optimal exposure
      for maximum initial fragmentation. Repair kinetics can also be analyzed through a
      time-course regimen.

PMID- 15502218
TI  - Analysis of in vivo mutation in the hprt and tk genes of mouse lymphocytes.
AB  - Determining mutant frequencies in endogenous reporter genes is a tool for
      identifying potentially genotoxic environmental agents and discovering phenotypes
      prone to genomic instability and diseases, such as cancer. Here we describe a
      high-throughput method for identifying mouse spleen lymphocytes having mutations
      in the endogenous X-linked hypoxanthine-guanine phosphoribosyltransferase (Hprt)
      gene and the endogenous autosomal thymidine kinase (Tk) gene. The selective
      expansion of mutant lymphocytes is based on the phenotypic properties of Hprt-
      and Tk-deficient cells. The same procedure can be utilized for quantitating Hprt
      mutations in most strains of mice (and, with minor changes, in other mammalian
      species), whereas mutations in the Tk gene can be determined only in transgenic
      mice that are heterozygous for inactivation of this gene. Expanded mutants can be
      further used to classify the types of mutations in the Tk gene (small intragenic
      mutations vs large chromosomal mutations) and to determine the nature of
      intragenic mutation in both the Hprt and Tk genes.

PMID- 15502219
TI  - Quantifying in vivo somatic mutations using transgenic mouse model systems.
AB  - This chapter describes the use of the bacteriophage cII positive selection assay
      with the MutaMouse transgenic model system. The assay is similar to others
      involving a transgenic target, including the cII and lacI assays in the Big
      Blue(R) Mouse, lacZ in the MutaMouse, and the gpt delta assay. Briefly, high
      molecular-weight DNA is purified from the tissue of interest and used as
      substrate during in vitro packaging reactions, in which the lambda transgenes are
      excised from the genome and assembled into viable phage. Phage containing the
      mutational targets are then adsorbed into an appropriate bacterial host, and
      mutations sustained in vivo are evidenced by either standard recombinant
      screening or selection assays. Mutant frequencies are reported as the ratio of
      mutant phage to total phage units analyzed. The lambda-based transgenic mouse
      assays are used to study and characterize in vivo mutagenesis, as well as for
      mutagenicity assessment. The models permit the enumeration of mutations sustained
      in virtually any tissue of the mouse and are sensitive and robust. Application of
      the assays is simple, not requiring resources beyond those commonly found in most
      academic laboratories.

PMID- 15502220
TI  - Methods for detecting somatic mutations in vitro: the human T-cell cloning assay
      selecting for HPRT mutants.
AB  - The T-cell cloning assay, which detects mutations in the gene for hypoxanthine
      guanine phosphoribosyltransferase (HPRT), is the most well-developed reporter
      system for studying specific locus mutation in human somatic cells. The assay is
      based on a mitogen- and growth factor-dependent clonal expansion of peripheral T
      lymphocytes in which the 6-thioguanine-resistant HPRT mutants can be selected,
      enumerated, and collected for molecular analysis of their mutational nature. The
      assay provides a unique tool for studying in vivo and in vitro mutagenesis and
      for investigating the functional impact of common polymorphisms in metabolism and
      repair genes. The present chapter presents a simple and reliable method for the
      enumeration of HPRT mutant frequency induced in vitro without using any source of
      recombinant interleukin-2. The other main feature is that only truly induced and
      unique mutants are collected for further analysis.

PMID- 15502221
TI  - Molecular analysis of mutations in the human HPRT gene.
AB  - The HPRT assay uses incorporation of toxic nucleotide analogs to select for cells
      lacking the purine scavenger enzyme hypoxanthine-guanine
      phosporibosyltransferase. A major advantage of this assay is the ability to
      isolate mutant cells and determine the molecular basis for their functional
      deficiency. Many types of analyses have been performed at this locus: the current
      protocol involves generation of a cDNA and multiplex PCR of each exon, including
      the intron/exon junctions, followed by direct sequencing of the products. This
      analysis detects point mutations, small deletions and insertions within the gene,
      mutations affecting RNA splicing, and the products of illegitimate V(D)J
      recombination within the gene. Establishment of and comparisons with mutational
      spectra hold the promise of identifying exposures to mutation-inducing
      genotoxicants from their distinctive pattern of gene-specific DNA damage at this
      easily analyzed reporter gene.

PMID- 15502222
TI  - Simultaneous quantification of t(14;18) and HPRT exon 2/3 deletions in human
      lymphocytes.
AB  - Specific recurring chromosomal translocations and deletions are found in a
      variety of cancers. In hematopoietic malignancies, many of these chromosomal
      aberrations result from mistakes involving V(D)J recombination. V(D)J
      recombination is required for the formation of functional T-cell receptor genes
      in T cells and antibody genes in B cells. This is an inherently dangerous
      process, however, because double-strand breaks are introduced into the
      chromosomes. Molecular evidence indicates that failure of the fidelity of this
      process results in the activation of proto-oncogenes or the inactivation of tumor
      suppressor genes. Here we describe sensitive, quantitative PCR assays for the
      measurement of such events in human lymphocytes. One assay measures the frequency
      of t(14;18) translocations that result in the dysfunctional regulation of the
      antiapoptotic gene BCL-2. The other assay measures the frequency of a deletion
      caused by illegitimate V(D)J recombination in the X-linked HPRT gene.

PMID- 15502223
TI  - The GPA in vivo somatic mutation assay.
AB  - The glycophorin A (GPA) assay concurrently detects and quantifies two types of
      erythrocytes with variant phenotypes at the autosomal locus responsible for the
      polymorphic MN blood group. It uses a pair of allele-specific monoclonal
      antibodies and flow cytometry to analyze a standard population of 5 million cells
      efficiently. The two phenotypes detected are simple allele loss and allele loss
      followed by reduplication of the remaining allele; both are consistent with the
      mechanisms underlying "loss of heterozygosity" at tumor suppressor genes. The
      assay is an intermediate biomarker of biological effect, meaning that it
      integrates both exposure and biological response. It has been applied to
      populations with a known or suspected genotoxic exposure, to patients with
      hereditary syndromes causing predisposition to cancer (in which the assay has
      begun to be moved from validation mode to application), and to patients
      manifesting a disease endpoint, i.e., cancer.

PMID- 15502224
TI  - Flow cytometric measurement of mutant T cells with altered expression of TCR:
      detecting somatic mutations in humans and mice.
AB  - Spontaneously generated mutant T cells defective in T-cell receptor (TCR) gene
      expression are detectable at the frequency of 10(-4) in vivo, and the mutant
      fractions are dose-dependently increased by exposure to genotoxic substances such
      as ionizing radiation. Mutant cells with altered expression of TCR-alpha or -beta
      among CD4+ T cells can be detected as CD3-/CD4+ cells by two-color flow cytometry
      using anti-CD3 and anti-CD4 monoclonal antibodies labeled with different
      fluorescent dyes, because an incomplete TCRalphabeta/CD3 complex cannot be
      transported to the cellular membrane. This flow cytometric mutation assay can be
      applied to CD4+ T cells from human peripheral blood and mouse spleen. Methods for
      both preparation of target cells and detection of the mutant cells are described.

PMID- 15502225
TI  - Mutation screening of the TP53 gene by temporal temperature gradient gel
      electrophoresis.
AB  - A protocol for detection of mutations in the TP53 gene using temporal temperature
      gradient gel electrophoresis (TTGE) is described. TTGE is a mutation detection
      technique that separates DNA fragments differing by single base pairs according
      to their melting properties in a denaturing gel. It is based on constant
      denaturing conditions in the gel combined with a temperature gradient during the
      electrophoretic run. This method combines some of the advantages of the related
      techniques denaturing gradient gel electrophoresis (DGGE) and constant denaturant
      gel electrophoresis (CDGE) and eliminates some of the problems. The result is a
      rapid and sensitive screening technique that is robust and easily set up in
      smaller laboratory environments.

PMID- 15502226
TI  - Analysis of K-RAS and P53 mutations in sputum samples.
AB  - Mutations in the P53 tumor suppressor gene and the K-RAS oncogene have frequently
      been found in sputum and bronchoalveolar lavage (BAL) samples of lung cancer
      patients, and also in samples from patients prior to presenting clinical symptoms
      of lung cancer, suggesting they may provide useful biomarkers for early lung
      cancer diagnosis. However, the detection of these mutations has been complicated
      by the fact that they often occur in only a small fraction of epithelial cells
      among sputum cells, and, in the case of the P53 gene, inactivating mutations may
      occur at many codons. This chapter describes methods to identify P53 and K-RAS
      mutations present in low fractions of epithelial cells among the excess of other
      cell types in sputum samples from lung cancer patients.

PMID- 15502227
TI  - Allele-specific competitive blocker-PCR detection of rare base substitution.
AB  - Methods that detect rare base substitutions within populations of DNA molecules
      are valuable tools for studying the DNA-damaging effects of chemicals and for
      pool screening for single-nucleotide polymorphisms. Allele-specific competitive
      blocker-polymerase chain reaction (ACB-PCR) uses a mutant-specific PCR primer
      with more 3'-terminal mismatches to an abundant or wild-type sequence than to a
      rare or mutant sequence in order to amplify specifically an allele that differs
      from the wild-type by a single base pair. ACB-PCR reactions include a blocker
      primer to reduce the amount of background signal generated from the abundant wild
      type template. The nonextendable blocker primer preferentially anneals to the
      wild-type DNA sequence, thereby excluding the annealing of the extendable mutant
      specific primer to the wild-type sequence. Inclusion of single-strand DNA binding
      protein in the ACB-PCR reaction and use of the Stoffel fragment of Taq DNA
      polymerase both significantly increase allele discrimination. The concurrent
      analysis of mutant fraction standards and equivalent PCR products amplified from
      genomic DNA samples makes ACB-PCR a quantitative method that can detect a base
      pair substitution in the presence of a 105-fold excess of wild-type DNA. Methods
      for the ACB-PCR measurement of the mouse H-ras codon 61 CAA --> AAA mutation are
      presented.

PMID- 15502228
TI  - Gel-based nonradioactive single-strand conformational polymorphism and mutation
      detection: limitations and solutions.
AB  - Single-strand conformation polymorphism (SSCP) for screening mutations/single
      nucleotide polymorphisms (SNPs) is a simple, cost-effective technique, saving an
      expensive exercise of sequencing each and every PCR reaction product and
      assisting in choosing only the amplicons of interest with expected mutation. The
      principle of detection of small changes in DNA sequences is based on the changes
      in single-strand DNA conformations. The changes in electrophoretic mobility that
      SSCP detects are sequence-dependent. The limitations faced in SSCP range from the
      routine polyacrylamide gel electrophoresis (PAGE) problems to the problems of
      resolving mutant DNA bands. Both these problems could be solved by controlling
      PAGE conditions and by varying physical and environmental conditions such as pH,
      temperature, voltage, gel type and percentage, addition of additives or
      denaturants, and others. Despite much upgrading of the technology for mutation
      detection, SSCP continues to remain the method of choice to analyze mutations and
      SNPs in order to understand genomic variations, spontaneous and induced, and the
      genetic basis of diseases.

PMID- 15502229
TI  - Detection and characterization of oncogene mutations in preneoplastic and early
      neoplastic lesions.
AB  - Although it has been more than 20 yr since its discovery, the ras family of genes
      has not yet lost its impact on basic and clinical oncology. These genes remain
      central to the field of molecular oncology as tools for investigating
      carcinogenesis and oncogenic signaling, as powerful biomarkers for the
      identification of those who have or are at high risk of developing cancer, and as
      oncogene targets for the design and development of new chemotherapeutic drugs.
      Mutational activation of the K-RAS proto-oncogene is an early event in the
      development and progression of the colorectal, pancreatic, and lung cancers that
      are the major causes of cancer death in the world. The presence of point
      mutational "hot spots" at sites necessary for the activation of this proto
      oncogene has led to the development of a number of highly sensitive PCR-based
      methods that are feasible for the early detection of K-RAS oncogene mutations in
      the clinical setting. In light of these facts, mutation at the K-RAS oncogene has
      the potential to serve as a useful biomarker in the early diagnosis and risk
      assessment of cancers with oncogenic Ras signaling. This chapter describes a
      highly sensitive method for detecting mutant K-RAS, enriched PCR, and its
      application to early detection of this oncogene in preneoplastic and early
      neoplastic lesions of the colon and rectum.

PMID- 15502230
TI  - Detection of DNA double-strand breaks and chromosome translocations using
      ligation-mediated PCR and inverse PCR.
AB  - Current techniques for examining the global creation and repair of DNA double
      strand breaks are restricted in their sensitivity, and such techniques mask any
      site-dependent variations in breakage and repair rate or fidelity. We present
      here a system for analyzing the fate of documented DNA breaks, using the MLL gene
      as an example, through application of ligation-mediated PCR. Here, a simple
      asymmetric double-stranded DNA adapter molecule is ligated to experimentally
      induced DNA breaks and subjected to seminested PCR using adapter and gene
      specific primers. The rate of appearance and loss of specific PCR products allows
      detection of both the break and its repair. Using the additional technique of
      inverse PCR, the presence of misrepaired products (translocations) can be
      detected at the same site, providing information on the fidelity of the ligation
      reaction in intact cells. Such techniques may be adapted for the analysis of DNA
      breaks introduced into any identifiable genomic location.

PMID- 15502231
TI  - Microsatellite instability: an indirect assay to detect defects in the cellular
      mismatch repair machinery.
AB  - The DNA mismatch repair (MMR) pathway plays a prominent role in the correction of
      errors made during DNA replication and genetic recombination and in the repair of
      small deletions and loops in DNA. Mismatched nucleotides can occur by replication
      error, damage to nucleotide precursors, damage to DNA, or during heteroduplex
      formation between two homologous DNA molecules in the process of genetic
      recombination. Defects in MMR can precipitate instability in simple sequence
      repeats (SSRs), also referred to as microsatellite instability (MSI), which
      appears to be important in certain types of cancers, both spontaneous and
      hereditary. Variation in the highly polymorphic alleles of specific
      microsatellite repeats can be identified using PCR with primers derived from the
      unique flanking sequences. These PCR products are analyzed on denaturing
      polyacrylamide gels to resolve differences in allele sizes of more than 2 bp.
      Although (CA)n repeats are the most abundant class among dinucleotide SSRs,
      trinucleotide and tetranucleotide repeats are also frequent. These polymorphic
      repeats have the advantage of producing band patterns that are easy to analyze
      and can be used as an indication of a possible MMR defect in a cell. The presumed
      association between such allelic variation and an MMR defect should be confirmed
      by molecular analysis of the structure and/or expression of MMR genes.

PMID- 15502232
TI  - Unscheduled DNA synthesis: a functional assay for global genomic nucleotide
      excision repair.
AB  - The unscheduled DNA synthesis (UDS) assay measures a cell's ability to perform
      global genomic nucleotide excision repair (NER). This chapter provides
      instructions for the application of this technique in living cells by creating 6
      4 photoproducts and pyrimidine dimers using UVC irradiation, then allowing for
      their repair. Repair is quantified by the amount of radioactive thymidine
      incorporated after this insult, and the length of time allowed for this
      incorporation is specific for repair of particular lesions. Radioactivity is
      evaluated by grain counting after autoradiography. The results are used to
      diagnosis repair-deficient disorders clinically and provide a basis for
      investigation of repair deficiency in human tissues or tumors. At the present
      time, no other functional assay is available that directly measures the capacity
      to perform NER on the entire genome without the use of specific antibodies. Since
      live cells are required for this assay, explant culture techniques must be
      previously established. Host cell reactivation, as discussed in Chapter 28, is
      not an equivalent technique, as it specifically measures transcription-coupled
      repair at active genes, a subset of total NER.

PMID- 15502233
TI  - Analysis of DNA repair using transfection-based host cell reactivation.
AB  - Host cell reactivation (HCR) is a transfection-based assay in which intact cells
      repair damage localized to exogenous DNA. This chapter provides instructions for
      the application of this technique using UV irradiation as a source of damage to a
      luciferase reporter plasmid. Through measurement of the activity of a reporter
      enzyme, the amount of damaged plasmid that a cell can "reactivate" or repair and
      express can be quantitated. Different DNA repair pathways can be analyzed by this
      technique by damaging the reporter plasmid in different ways. Because it involves
      repair of a transcriptionally active gene, when applied to UV damage the HCR
      assay measures the capacity of the host cells to perform transcription-coupled
      repair (TCR), a subset of the overall nucleotide excision repair pathway that
      specifically targets transcribed gene sequences.

PMID- 15502234
TI  - An immunoassay for measuring repair of ultraviolet photoproducts.
AB  - A method is described that makes use of a polyclonal antiserum to measure repair
      of the principal photoproducts induced in DNA by short-wave ultraviolet light
      (UVC)-pyrimidine-pyrimidone 6-4 photoproducts ([6-4]PPs) and cyclobutane
      pyrimidine dimers (CPDs). DNA extracted from irradiated cells is applied to a
      nitrocellulose dot blot and quantitated using an enzyme-conjugated secondary
      antibody and a color assay. Although the polyclonal antiserum contains antibodies
      to both [6-4]PPs and CPDs, repair of these can be measured separately by
      differential destruction or repair of one or other photoproduct. The method is
      useful for measuring repair in total genomic DNA and is sufficiently sensitive to
      measure repair of damage induced by doses of 10 J/m2 of UVC and less. The method
      is very versatile and has been used to measure repair in human cells, yeasts,
      plants, archaea, bacteria, and filamentous fungi.

PMID- 15502235
TI  - Analysis of DNA double-strand break repair by nonhomologous end joining in cell
      free extracts from mammalian cells.
AB  - Double-strand breaks (DSBs) in genomic DNA are induced by ionizing radiation or
      radiomimetic drugs, but they also occur spontaneously during the cell cycle at
      quite significant frequencies. In vertebrate cells, nonhomologous DNA end joining
      (NHEJ) is considered the major pathway of DSB repair. NHEJ is able to rejoin two
      broken DNA termini directly end-to-end irrespective of sequence and structure.
      Genetic studies in various radiosensitive and DSB repair-deficient hamster cell
      lines have yielded insights into the factors involved in NHEJ. Studies in cell
      free systems derived from Xenopus eggs and mammalian cells have allowed the
      dissection of the underlying mechanisms. In the present chapter, we describe a
      protocol for the preparation of whole cell extracts from mammalian cells and a
      plasmid-based in vitro assay that permits the easy analysis of the efficiency and
      fidelity of DSB repair via NHEJ in different cell types.

PMID- 15502236
TI  - Measuring recombination proficiency in mouse embryonic stem cells.
AB  - A method is presented to measure homologous recombination in mouse embryonic stem
      cells by both gene targeting and short-tract gene conversion of a double-strand
      break. A fluorescence-based reporter is first gene targeted to the Hprt locus in
      a quantifiable way. A homing endonuclease expression vector is then introduced to
      generate a double-strand break, the repair of which is also quantifiable.

PMID- 15502237
TI  - Strategies for measurement of biotransformation enzyme gene expression.
AB  - The analysis of gene expression is an integral part of any research
      characterizing gene function. A wide variety of techniques have been developed
      for this purpose, each with their own advantages and limitations. This chapter
      seeks to provide an overview of some of the most recent as well as conventional
      methods to quantitate gene expression. These approaches include Northern blot
      analysis, ribonuclease protection assay (RPA), reverse transcription polymerase
      chain reaction, expressed sequence tag (EST) sequencing, differential display,
      cDNA arrays, and the serial analysis of gene expression (SAGE). Current
      applications of the information derived from gene expression studies require
      assays to be adaptable for the quantitative analysis of a large number of samples
      and end points within a short period coupled with cost effectiveness. A
      comparison of some of these features of each analytical approach as well as their
      advantages and disadvantages has also been provided.

PMID- 15502238
TI  - Genotyping technologies: application to biotransformation enzyme genetic
      polymorphism screening.
AB  - Pharmacogenomics encompasses several major areas: the study of polymorphic
      variations in drug response and disease susceptibility, identification of the
      effects of drugs/xenobiotics at the genomic level, and genotype/phenotype
      associations. The most common type of human genetic variations is single
      nucleotide polymorphisms (SNPs). Several novel approaches to detection of SNPs
      are currently available. The range of new methods includes modifications of
      several conventional techniques, such as PCR, mass spectrometry (ms), and
      sequencing, as well as more innovative technologies such as fluorescence
      resonance energy transfer (FRET) and microarrays. The application of each of
      these techniques is largely dependent on the number of SNPs to be screened and
      sample size. The current chapter presents an overview of the general concepts of
      a variety of genotyping technologies, with an emphasis on the recently developed
      methodologies, including a comparison of the advantages, applicability, cost
      efficiency, and limitations of these methods.

PMID- 15502239
TI  - TaqMan fluorogenic detection system to analyze gene transcription in autopsy
      material.
AB  - Real-time RT-PCR using a TaqMan fluorogenic detection system is a simple and
      sensitive assay for quantitative analysis of gene transcription. This method is
      of potential usefulness in quantifying mRNA of a target gene in autopsy material
      that has undergone only a small amount of postmortem degradation. The TaqMan
      fluorogenic detection system can monitor PCR in real time using a dual-labeled
      fluorogenic hybridization probe (TaqMan probe) and a polymerase with 5'-3'
      exonuclease activity. The procedures of the quantitative RT-PCR are as follows:
      RNA is extracted from autopsy material and used to synthesize cDNA by an RT
      reaction, and the target of interest is amplified and detected by the real-time
      PCR. The absolute amount of target mRNA in the sample is then determined relative
      to a standard curve. This chapter describes the methodology of the TaqMan
      fluorogenic detection system in handling autopsy material in the gene
      transcription assay.

PMID- 15502240
TI  - Development of quantitative reverse transcriptase PCR assays for measuring gene
      expression.
AB  - Real-time, quantitative reverse transcriptase (RT)-PCR is a very useful and
      powerful technology for analysis of gene expression. At a first pass, real-time
      PCR appears to be a simple extension of regular PCR, and it should therefore be
      easy for an experienced PCR user to convert to quantitative assays. In practice,
      however, our experience would indicate that this is not usually the case, and
      most novice real-time PCR users run into problems even though they are very
      capable at regular PCR. One problem is that, unlike Northern blots, which are
      technically difficult but typically either work or do not, real-time PCR assays,
      even poorly designed ones, usually give data. Unfortunately, these data, or their
      interpretation, may be erroneous, since there are many potential pitfalls that
      need to be avoided when designing and using real-time PCR for measurement of gene
      expression. The purpose of this chapter is not to try to discuss the complexities
      of real-time PCR in detail (which would require a whole book), but, instead, to
      provide a simple outline for the development of real-time PCR assays. If
      followed, these guidelines should allow the reader to develop real-time PCR
      assays that avoid the most common pitfalls and that are capable of producing
      reliable and accurate gene expression data.

PMID- 15502241
TI  - Quantification of selective phosphatidylserine oxidation during apoptosis.
AB  - Membrane phospholipids are gaining increasing attention as important mediators in
      a variety of signal transduction processes. Oxidation and changes in membrane
      topography of lipids are probably important elements in the regulation of
      phospholipid-dependent signaling. Phosphatidylserine (PS), in particular, is
      implicated in the regulation of macrophage-dependent clearance of apoptotic cell
      "corpses" in a pathway probably mediated by selective oxidation and translocation
      of PS in the plasma membrane. Here we describe our highly sensitive and specific
      assay to measure differential lipid peroxidation in individual phospholipid
      classes in live cells using metabolic integration of the fluorescent oxidation
      sensitive fatty acid analog cis-parinaric acid (cis-PnA) and resolution of
      specific phospholipids by high-performance liquid chromatography (HPLC). These
      experimental approaches can provide insight into the roles and mechanisms of PS
      oxidation in the identification and clearance of apoptotic cells.

PMID- 15502242
TI  - Quantitative method of measuring phosphatidylserine externalization during
      apoptosis using electron paramagnetic resonance spectroscopy and annexin
      conjugated iron.
AB  - We present here the application of a novel assay that measures the absolute
      amount of phosphatidylserine (PS) externalized on the surface of cells. Although
      the assay is based on the same annexin binding principle as the fluorescent flow
      cytometry assay, we use paramagnetic iron as the ultimate reporter molecule,
      establishing a linear relationship between signal amplitude and amount of PS on
      the cell surface, allowing a quantitative assay of PS externalization over a wide
      dynamic range. The application of this technique, alone and in concert with the
      PS oxidation method presented in the previous chapter, will greatly aid in
      studying the mechanistic connection between lipid peroxidation and translocation
      events during apoptosis.

PMID- 15502243
TI  - Detection of programmed cell death in cells exposed to genotoxic agents using a
      caspase activation assay.
AB  - Many environmental toxins cause DNA damage. Cells that have sustained significant
      DNA damage must attempt to repair the damage prior to replication, in which
      aberrant base incorporation can result in an irreversible mutation. If a cell
      cannot repair the damage, however, it may commit suicide through a genetically
      regulated programmed cell death (PCD) pathway. Crucial to the ultimate execution
      of PCD is a family of cysteine proteases called caspases. Activation of these
      enzymes occurs late in the PCD pathway, when a cell can no longer avoid cell
      death, but earlier than other PCD markers, such as morphological changes or DNA
      fragmentation. This protocol details a method for using fluorochrome-conjugated
      caspase inhibitors for the detection of activated caspases in intact cells using
      fluorescent microscopy.

PMID- 15502244
TI  - Mass spectrometry and biomarker development.

PMID- 15502245
TI  - Advancement of biomarker discovery and validation through the HUPO plasma
      proteome project.
AB  - The Human Proteome Organization (HUPO) Plasma Proteome Project has mounted a
      Pilot Phase focussed on key problems essential for standardization of specimen
      collection, specimen handling, choice of fractionation and analysis technologies,
      and search engines and databases for protein identifications. This international
      collaboration will lay the groundwork for many large-scale clinical and
      epidemiological studies of health and disease.

PMID- 15502246
TI  - A rational approach for discovering and validating cancer markers in very small
      samples using mass spectrometry and ELISA microarrays.
AB  - Identifying useful markers of cancer can be problematic due to limited amounts of
      sample. Some samples such as nipple aspirate fluid (NAF) or early-stage tumors
      are inherently small. Other samples such as serum are collected in larger volumes
      but archives of these samples are very valuable and only small amounts of each
      sample may be available for a single study. Also, given the diverse nature of
      cancer and the inherent variability in individual protein levels, it seems likely
      that the best approach to screen for cancer will be to determine the profile of a
      battery of proteins. As a result, a major challenge in identifying protein
      markers of disease is the ability to screen many proteins using very small
      amounts of sample. In this review, we outline some technological advances in
      proteomics that greatly advance this capability. Specifically, we propose a
      strategy for identifying markers of breast cancer in NAF that utilizes mass
      spectrometry (MS) to simultaneously screen hundreds or thousands of proteins in
      each sample. The best potential markers identified by the MS analysis can then be
      extensively characterized using an ELISA microarray assay. Because the microarray
      analysis is quantitative and large numbers of samples can be efficiently
      analyzed, this approach offers the ability to rapidly assess a battery of
      selected proteins in a manner that is directly relevant to traditional clinical
      assays.

PMID- 15502247
TI  - Proteomics approaches to identify tumor antigen directed autoantibodies as cancer
      biomarkers.
AB  - The identification of autoantibodies to tumor cell proteins by proteomics
      approaches has great potential impact on cancer biomarker discovery. The humoral
      immune response represents a form of biological amplification of signals that are
      otherwise weak due to very low concentrations of antigen, especially in the early
      stages of cancers. In addition, proteomics can detect immunoreactivity directed
      against protein post-translational modifications. Two-dimensional gel based
      Western blots, protein antigen microarrays, and multiplex ELISA reactions have
      been applied by our group to antigen based biomarker detection and validation.
      The latter two are based on liquid-phase separations that are suitable for
      automation. This work has resulted in the identification of numerous cancer
      biomarker candidates. Large clinical studies are currently planned to establish
      their value in early cancer diagnosis.

PMID- 15502248
TI  - The use of laser capture microscopy in proteomics research--a review.

PMID- 15502249
TI  - Update on diabetes mellitus.
AB  - Diabetes mellitus is a complex multi-system disorder that may be classified as
      autoimmune mediated type 1 diabetes, or as insulin resistance associated type 2
      diabetes. In type 1 diabetes, there is selective loss of the beta cells within
      the endocrine islets, as a consequence of T-cell and cytokine mediated
      destruction of these cells, perhaps in conjunction with destruction of the peri
      islet Schwann cells. In type 2 diabetes, the etiology of the resistance ranges
      from post-receptor defects in the insulin signaling pathway to excessive
      production of adipocyte derived cytokines that antagonize insulin action to
      mitochondrial defects that interfere with glucose disposal. Proteome based
      technologies are providing new insights into these defects.

PMID- 15502250
TI  - Heart disease, clinical proteomics and mass spectrometry.
AB  - Heart disease is the leading cause of mortality and morbidity in the world. As
      such, biomarkers are needed for the diagnosis, prognosis, therapeutic monitoring
      and risk stratification of acute injury (acute myocardial infarction (AMI)) and
      chronic disease (heart failure). The procedure for biomarker development involves
      the discovery, validation, and translation into clinical practice of a panel of
      candidate proteins to monitor risk of heart disease. Two types of biomarkers are
      possible; heart-specific and cardiovascular pulmonary system monitoring markers.
      Here we review the use of MS in the process of cardiac biomarker discovery and
      validation by proteomic analysis of cardiac myocytes/tissue or serum/plasma. An
      example of the use of MS in biomarker discovery is given in which the albumin
      binding protein sub-proteome was examined using MALDI-TOF MS/MS. Additionally, an
      example of MS in protein validation is given using affinity surface enhanced
      laser desorption ionization (SELDI) to monitor the disease-induced post
      translational modification and the ternary status of myocyte-originating protein,
      cardiac troponin I in serum.

PMID- 15502252
TI  - Caregiver reports of common symptoms in children following a traumatic brain
      injury.
AB  - This study describes the common symptoms in children and adolescents following a
      traumatic brain injury (TBI) as reported by their primary caregivers. Utilizing
      data from a large-scale state demonstration project, 681 children who had
      sustained a TBI were ascertained from both Hospital Emergency Departments (n =
      409) and Pediatric Inpatient settings (n = 272). The sample ranged in age from
      infancy to 18 years, was largely male (59.7%), and had equal numbers of Caucasian
      and minority patients. Most of the participants experienced a mild TBI (83%),
      with about 5.1% being moderate and 12% severe. Caregivers described the presence
      of current symptoms (neurological, neurocognitive, behavioral, school problems)
      using a series of dichotomous questions regarding their child via a structured
      telephone interview at 1, 4, and 10 months post-injury. Inpatient children were
      described as manifesting more symptoms at each of the follow-up time points than
      their ED counterparts. At 1 month inpatients were described as having more
      symptoms across all 4 domains. At 4 and 10 months, the inpatients were described
      as having more neurocognitive symptoms and as not returning to school on a full
      time basis, with behavior problems approaching significance at the 10-month
      point. A large number of individuals from both groups also reported persistent
      symptoms 10 months post-injury including headaches, attention and memory
      problems, low frustration tolerance, sleep problems, personality changes, and new
      school problems. Practical implications of these findings for the ongoing
      management of these children are discussed.

PMID- 15502253
TI  - Developing a follow-up survey focused on participation of children and youth with
      acquired brain injuries after discharge from inpatient rehabilitation.
AB  - OBJECTIVE: To describe the development and content of a follow-up survey designed
      to monitor needs and outcomes of children and youth with acquired brain injuries
      (ABI) and their families after discharge from inpatient rehabilitation.
      Preliminary findings pertaining to the core measure of the survey that focused on
      participation in home, school and community life will be presented as well.
      METHODS: The follow-up survey was completed by sixty caregivers of children with
      ABI discharged from one pediatric inpatient rehabilitation program in the
      Northeast, USA. Time since discharge ranged from 4 months to 6.5 years.
      Children's ages at discharge ranged from 4 months to 21 years and at follow-up
      ranged from 3 to 27 years. RESULTS: Preliminary evidence of reliability, internal
      consistency and criterion-related validity was demonstrated for the participation
      measure. Results from exploratory factor analyses and Rasch analyses suggest that
      the participation measure may be measuring essentially one construct that may
      encompass two dimensions: Participation in movement-related activities and
      participation in communication and school-based social activities. Age, activity
      performance and child and environmental factors were associated with children's
      overall extent of participation. CONCLUSIONS: The results presented are
      preliminary yet promising. The follow-up survey is being further developed and
      tested. Future research also will investigate clinical utility, differences in
      scores among children and youth with different diagnostic conditions, and
      feasibility of creating separate versions of the participation measure for
      different age groups.

PMID- 15502254
TI  - The Pediatric Acquired Brain Injury Community Outreach Program (PABICOP) - an
      innovative comprehensive model of care for children and youth with an acquired
      brain injury.
AB  - The Pediatric Acquired Brain Injury Community Outreach Program - an innovative,
      comprehensive model of care for children and youth with an acquired brain injury
      is described. The background to the formation of the idea is delineated and the
      current function of the model given. Future directions are discussed. The program
      addresses the needs and issues of children and youth with an acquired brain
      injury and their families. Subsequent literature supports the concept of care
      that this program espouses.

PMID- 15502255
TI  - Improving educational services for students with TBI through statewide consulting
      teams.
AB  - Since 1991, when Traumatic Brain Injury (TBI) was established as a disability
      category under IDEA, educators nationwide have become increasingly aware of the
      unique and complex challenges these students present. Yet professionals,
      advocates and family members share a growing concern that the instructional needs
      of these students are not being met. School personnel serving these students need
      systematic support that includes both information about specific aspects of the
      student's disability and access to expert technical assistance. The goal of the
      TBI Team model, as developed and implemented in Iowa, Kansas, and Oregon, is to
      make available to schools statewide a group of well-trained peer consultants who
      can provide in-service training and ongoing consultation. The TBI Team model has
      four components: (a) needs assessment, (b) team recruitment, (c) team training,
      and (d) evaluation of both implementation and outcomes. Trained Team members
      provide in-service training, classroom consultation, and information and
      resources for school staff and parents. Team operations are maintained and
      supported through a central office at the Department of Education. Evaluation
      data suggest that the Team model is a cost effective and efficient approach to
      supporting teachers who work with students with TBI.

PMID- 15502256
TI  - The potential of electronic organizers as a tool in the cognitive rehabilitation
      of young people.
AB  - Youths who have traumatic brain injury (TBI) or mental retardation and other
      developmental disabilities often experience cognitive challenges in using memory
      and organization for learning, managing daily routines, or conducting social
      interactions. This article presents the results of a survey of 53 youth-parent
      teacher triads probing their views regarding the youth's relationship with
      technology. Since the sample is small, results should be viewed with caution, yet
      keeping in mind the study presents some of the only data available on the use of
      generic technologies with youths who have disabilities. Primary findings
      indicate: 1) youths use a variety of technologies and are more likely to be
      exposed to computers than cell phones or personal data assistants respectively;
      2) youths with finger, reading, and copying skills use more technologies; 3)
      youths value many varied features of technology, but rated most highly good
      technical support, simple learning requirements, capacity to store information,
      and long battery life. The data also indicated that the most common memory and
      organization strategy the youths used was "someone does it for me".

PMID- 15502257
TI  - Theory of Mind and social beliefs in adolescents with traumatic brain injury.
AB  - Impairments in social performance are common consequences of TBI, yet the
      neuropsychological basis of these impairments is not well understood. This is
      particularly true for adolescents, who have the highest incidence of TBI and are
      at a critical stage of developing social and relationship skills. To address
      this, adolescents with TBI were compared to their typically developing peers on a
      social cognition task that included Theory of Mind (ToM) questions. As ToM may be
      necessary for the development of culture-specific social knowledge, the two
      groups also were compared in regard to their social beliefs. There were
      significant differences between injured and uninjured adolescents in social
      cognition, with group differences increasing as a function of the requirement for
      ToM. There were few differences in self-reported social knowledge and social
      beliefs. The implication of this discrepancy for the rehabilitation of
      adolescents with TBI is discussed.

PMID- 15502258
TI  - Social problem solving abilities and psychosocial impairment among individuals
      recuperating from surgical repair for severe pressure sores.
AB  - BACKGROUND/OBJECTIVES: The relationship of social problem solving abilities,
      health locus of control beliefs, and psychosocial impairment were examined among
      individuals with spinal cord injuries who were hospitalized following surgical
      repair of severe pressure sores. METHODS: Individuals were approached after
      surgical repair and completed measures of problem solving, health locus of
      control beliefs, and psychosocial impairment after admission to the
      rehabilitation hospital. RESULTS: The sample reported greater psychosocial
      impairment than observed in comparative data, but they did not differ from
      another sample in terms of health locus of control beliefs. Correlational
      analyses revealed that a negative orientation toward problem solving was
      significantly predictive of psychosocial impairment, consistent with prior
      research. However, a second study found persons assigned to a brief problem
      solving intervention did not differ on any measure from participants in a control
      group. DISCUSSION: Implications of these results are discussed from theoretical
      and clinical perspectives. Although social problem solving abilities were
      predictive of psychosocial impairment in a predicted direction, the lack of
      effects for the intervention suggests greater precision is needed to understand
      individual needs and to develop individualized intervention protocols.

PMID- 15502260
TI  - Motor system recovery: evidence from animal experiments, human functional imaging
      and clinical studies.

PMID- 15502259
TI  - Constraint-induced movement therapy for chronic stroke hemiparesis and other
      disabilities.
AB  - Constraint-Induced Movement Therapy (CI therapy) refers to a family of treatments
      for motor disability that combines constraint of movement, massed practice, and
      shaping of behavior to improve the amount of use of the targeted limb. CI therapy
      has controlled evidence for efficacy that supports its benefit for patients with
      chronic disability following central nervous system injury, regardless of their
      age or the interval since illness onset. Furthermore, the benefits transfer to
      real-world measures of limb use. Significant functional improvement may occur
      even after the patient has been treated with conventional physical therapy. In
      this paper we review the evidence for the efficacy of CI therapy, particularly
      for chronic stroke hemiparesis, but also for diverse other chronic disabling
      illnesses, including non-motor disorders such as phantom limb pain and aphasia.
      The adaptation of the therapy to the stroke clinic is described, along with a
      review of the neurophysiologic mechanisms that are postulated to underlie the
      treatment benefit (overcoming learned nonuse, plastic brain reorganization).
      Critical to the success of CI therapy is its modification according to disease
      factors, economic considerations, limitations of the practice setting, and the
      cognitive and physical status of the patient. We conclude by recommending future
      areas for research on CI therapy.

PMID- 15502261
TI  - The reorganization of the motor system in primates after the loss of a limb.
AB  - As a result of an extensive search, we were able to obtain a limited number of
      macaque monkeys, New World squirrel monkeys, and prosimian galagos years after
      they had received a therapeutic amputation of a forelimb or hindlimb as a
      treatment for injury. Forelimb or hindlimb regions of primary motor cortex, M1,
      were stimulated in these primates with microelectrodes using amounts of current
      just sufficient to evoke a movement. Results were compared to those obtained from
      normal primates or from M1 contralateral to the intact limb in the same primates.
      In all cases, more sites in M1 contralateral to the amputated limb evoked
      movements of the limb stump and muscle in the adjoining shoulder or hip. In two
      of the macaque monkeys, injections in M1 reveal more widespread intrinsic
      connections than in normal M1, and in several monkeys and galagos, injections of
      tracers in muscles of the stump, shoulder, or hip labeled spinal cord motor
      neurons that normally project to the distal limb. These anatomical results
      suggest that the functional changes in M1 following amputation are mediated in
      part by the formation of new connections.

PMID- 15502262
TI  - The interplay between behavior and neurodegeneration in rat models of Parkinson's
      disease and stroke.
AB  - The effects of extreme disuse or overuse of the limbs in rat models of
      Parkinson's disease and stroke are discussed. In unilaterally lesioned rats,
      immobilizing one forelimb in a cast forces complete disuse of this limb and
      extreme overuse of the uncasted limb. This procedure has diverse effects on
      histological and behavioral outcomes in these models, depending upon how and when
      it is applied relative to the lesion. Effects on behavioral outcome, post-lesion
      plasticity events, and expression of trophic factors are discussed. The effects
      of forced disuse or overuse vary among lesion types and can include
      neuroprotection, changes in synaptogenesis, or even exaggeration of tissue loss.
      The diversity of behavior-driven structural changes in the brain underscores the
      potential importance of carefully tailoring physical restorative therapy to
      specific neurological problems in order to optimize outcomes. In addition, we
      stress the need to recognize the reciprocal influence that behavior and the brain
      can have upon each other.

PMID- 15502263
TI  - Functional and cellular effects of environmental enrichment after experimental
      brain infarcts.
AB  - Our genes interact with environmental stimuli throughout our lives. The attitude
      and reaction to an acute cerebral trauma or stroke, as well as the pre-lesion
      life event and activities, can influence functional outcome. Although difficult
      to separate in adult human beings, genetic and environmental factors can be
      selectively evaluated in animal studies. Post-ischemic housing in an enriched
      environment, i.e. larger cages which allow both social interaction and various
      activities improves functional outcome, modifies gene activation, and increases
      dendrite branching and number of dendritic spines in pyramidal neurons in layers
      II-III in the contra-lateral cortex. Furthermore, it alters lesion-induced
      progenitor cell differentiation and interacts with neocortical transplantation,
      drug treatment and training. It is proposed that the interaction between
      environment and specific treatment needs more clinical attention, and that a
      general stimulating and positive environment is the optimal base for specific
      interventions in neurological rehabilitation.

PMID- 15502264
TI  - Noradrenergic modulation of hemiplegia: facilitation and maintenance of recovery.
AB  - This review presents data from laboratory studies and clinical trials indicating
      the efficacy of the "Noradrenergic Strategy" for enhancing recovery after
      cortical injury. Short-term acute treatment combining Physical Therapy (PT) with
      drugs increasing noradrenaline (NA) levels enhances recovery of hemiplegia in
      both laboratory studies and clinical trials which also report improved aphasia
      recovery. Importantly these effects endure even when treatment is initiated
      months after stroke onset. The hypothesized mechanisms included modulation of
      neuronal processes underlying "spontaneous" recovery since drugs reducing NA
      levels slow spontaneous recovery. The effect of some drugs change with time after
      sensorimotor cortex (SMCx) injury. Drugs reducing NA levels, including clonidine
      and prazosin, and GABA receptor agonists at doses having little effect early
      after injury, when administered to animals or stroke patients after "complete
      recovery" transiently reinstate the original symptoms. Reinstatement by prazosin
      remains unchanged after repeated testing for over six months in rat, and the
      deficits can be as severe as the first days after injury. This suggests
      "completed" recovery is an inaccurate label for an enduring "fragile" state. This
      transient reinstatement of symptoms may be useful for distinguishing causal from
      corollary relationships between symptoms and physiological processes proposed as
      mechanisms for recovery of function.

PMID- 15502265
TI  - Neuronal post-stroke plasticity in the adult.
AB  - Contrary to what previously believed, recent research advances have demonstrated
      that the adult brain has a certain capacity for plastic reorganization and self
      repair after a lesion such as cerebrovascular accidents. The mechanisms
      subtending post-stroke recovery are probably complex and operating at different
      levels, from molecular to synaptic to anatomical reorganization. The integrated
      use of functional neuroimaging techniques, by overcoming the limitations of each
      specific methodology is likely to shed much light on plasticity mechanisms. In
      this review we discuss the neuroanatomy and neurophysiology possibly underlying
      reorganization of the central nervous system, as well as the experimental
      evidence of "in vivo" post-stroke plasticity. Better understanding of these
      mechanisms can provide neurorehabilitation with powerful tools in designing and
      implementing new therapeutic approaches to stroke patients both in the acute and
      the chronic stages after a brain tissue lesion has occurred and stabilized.

PMID- 15502266
TI  - Reorganisation of cerebral circuits in human ischemic brain disease.
AB  - Animal experiments suggest that reorganisation of cerebral representations is the
      neurobiological basis of post-lesional recovery. In human ischemic brain disease
      recovery is a dynamic and sustained process beginning after stroke manifestation.
      The mechanisms underlying recovery can be investigated non-invasively in the
      human brain using functional neuroimaging and transcranial magnetic stimulation
      (TMS). In the acute stage, the mismatch area of the perfusion deficit and the
      impaired water diffusion as assessed by magnetic resonance imaging (MRI) shows
      the brain tissue that potentially can be rescued by thrombolysis or emergency
      carotid endarterectomy. Since spontaneous motor recovery is a function of the
      corticospinal tract integrity, early reperfusion of ischemic tissue is critical.
      In the subacute and chronic stage after stroke, recovery of motor function was
      shown to take place irrespective of a concomitant affection of the somatosensory
      system. Functional MRI with simultaneous recordings of the electromyogram
      provides evidence that the abnormal activation of motor and premotor cortical
      areas in both hemispheres related to finger movements has a large interindividual
      variability. As evident from TMS, recovery results from regression of
      perilesional inhibition and from remote intracortical disinhibition. Repetitive
      training, constraint induced training and motor imagery can augment recovery
      promoting a re-emerging activation in the affected hemisphere. Evolution of
      altered local perilesional and large-scale bihemispheric circuits appears to
      allow for post-lesional deficit compensation.

PMID- 15502267
TI  - Changes in motor system function and recovery after stroke.
AB  - Motor system impairments are common after stroke and are a major contributor to
      disability after stroke. Most patients show improvement in the weeks-months
      following a stroke. Understanding the neurobiological underpinnings of these
      behavioral gains may be useful for refining treatments that aim to improve
      outcome and reduce disability. A number of brain mapping studies have examined
      how stroke affects motor system function. Numerous changes have been identified
      in this setting and are reviewed herein, including reduced laterality, widespread
      changes across a distributed sensorimotor network, and a change in the site and
      size of key activation foci. Some of these changes have been found to correlate
      with features of injury, behavior, or treatment-induced behavioral gains. A
      current challenge is to extend these findings to improve clinical decision
      making.

PMID- 15502268
TI  - Cortical reorganization--effects of intensive therapy.
AB  - Recovery from hemiparesis after stroke largely depends on widespread functional
      and structural neuronal plasticity. Based on animal studies of rehabilitative and
      pharmacological interventions on recovery, recent neuroscientific findings
      suggest that new rehabilitative interventions may also have benefits by
      modulating neuroplastic mechanisms in stroke patients. Neurofunctional imaging
      methods such as Positron Emission Tomography (PET) and functional Magnetic
      Resonance Imaging (fMRI) as well as transcranial magnetic stimulation (TMS) now
      permit direct studies of training-induced plasticity in stroke patients.
      Prospectively conducted studies using these techniques have investigated how
      plasticity relates to recovery of motor function and how intensive training
      modulates cortical reorganization. Despite technical and methodological
      differences, consistent neuroanatomic findings on training-induced reorganization
      of the motor system have been reported. These discoveries have important
      implications for the future development of neurorehabilitative training methods.
      With continuously improving methods to study cortical reorganization and over 100
      randomized clinical trials on stroke rehabilitation published during the past
      five years, this promises to be an exciting time in stroke rehabilitation
      research.

PMID- 15502269
TI  - Non-invasive mapping of brain functions and brain recovery: applying lessons from
      cognitive neuroscience to neurorehabilitation.
AB  - Modern cognitive neuroscience provides a powerful framework in which biological
      models of recovery and neurorehabilitation can be constructed and tested. The
      widespread availability, relatively low cost and informativeness of functional
      magnetic resonance imaging (fMRI) has made it the most popular of the techniques
      available to help with this task. Here, on the basis of functional imaging
      studies of stroke, diffuse microvascular disease and multiple sclerosis, we argue
      that processes of motor control and learning in the healthy brain share common
      mechanisms with those for adaptive functional reorganisation during spontaneous
      recovery after brain injury or with neurorehabilitation. Relatively stringent
      criteria can be met to confirm that adaptive functional reorganisation limits
      disability even in the adult brain: functional brain changes are related to
      disease burden, can be found in patients with demonstrable pathology but no
      clinical deficits and can be defined (in motor cortex) even in the absence of
      volitional recruitment. Initial studies of neurorehabilitation responses using
      fMRI and transcranial magnetic stimulation demonstrate that adaptive
      reorganisation can be manipulated directly with both pharmacological and
      behavioural interventions. The combination of strategies based on a strong
      biological rational with monitoring their effects using highly informative
      functional brain imaging methods heralds a new era of scientifically-founded
      neurorehabilitation.

PMID- 15502270
TI  - Modulation of motor function and cortical plasticity in health and disease.
AB  - Basic science studies demonstrated mechanisms of plasticity and metaplasticity.
      More recent human studies identified some of these mechanisms as operating in
      multiple areas of human cognition, such as learning and memory, and in functional
      recovery from lesions in the CNS, as in stroke. One of the goals of
      neurorehabilitation is the translation of these principles into rational
      strategies to promote recovery of function. Understanding the mechanisms and
      functional role of human plasticity could lead to the development of therapeutic
      options in situations in which there is virtually no treatment alternative, as in
      chronic stroke. We review some of the work performed to better understand the
      substrates and mechanisms underlying cortical plasticity and discuss some
      experimental approaches to enhance cortical plasticity and recovery of function,
      like cortical stimulation.

PMID- 15502271
TI  - Lesion-induced and training-induced brain reorganization.
AB  - INTRODUCTION: A stroke may modulate motor cortex excitability. We examined if
      distinct ischemic brain lesions are associated with a specific pattern of
      excitability changes. We also investigated the effects of a rehabilitative
      therapy on motor excitability. METHODS: In stroke patients, the consequences of
      a) a lesion in the central somatosensory system, b) a cerebellar lesion and c) a
      two week period of Constraint-induced movement therapy (CIMT), on motor cortex
      excitability were studied. Transcranial magnetic stimulation techniques and
      functional magnetic resonance imaging (fMRI) were employed. RESULTS: Patients
      with a lesion in the primary somatosensory cortex or in the ventroposterolateral
      nucleus of the thalamus had a decreased intracortical inhibition on the affected
      side. Patients with lesions in the territory of the superior cerebellar artery
      had a loss of intracortical facilitation and an increase of intracortical
      inhibition. Patients with cortical lesions undergoing CIMT had a loss of
      intracortical inhibition prior to therapy. After CIMT, changes of ICI were
      stronger in the lesioned than in the non-lesioned hemisphere but could result
      either in an increase of ICI or a reduction of ICI. In three patients fMRI
      results showed that cortical activation was less post CIMT as compared to pre
      treatment activation. In parallel, ICI was reduced after treatment. CONCLUSIONS:
      Our results suggest that, physiologically, central somatosensory influence on the
      motor cortex is inhibitory. In contrast, the cerebellum normally exerts a
      facilitatory influence on the motor cortex. CIMT induces changes of intracortical
      excitability mainly in the affected hemisphere.

PMID- 15502272
TI  - Understanding the pattern of functional recovery after stroke: facts and
      theories.
AB  - Longitudinal studies show that almost all stroke patients experience at least
      some predictable degree of functional recovery in the first six months post
      stroke. However, the non-linear pattern as a function of time is not well
      understood. Several mechanisms are presumed to be involved, such as recovery of
      penumbral tissues, neural plasticity, resolution of diaschisis and behavioural
      compensation strategies. Rehabilitation is believed to modulate this logistic
      pattern of recovery, probably by interacting with these underlying processes.
      However, prediction models that are adjusted for the effects of time after stroke
      onset suggest that outcome is largely defined within the first weeks post stroke,
      although functional improvement has been found to extend beyond six months post
      stroke. In addition, kinematic studies show that functional improvement is more
      than recovery from impairments alone, suggesting that patients are able to
      improve in terms of gait or dexterity deficits using behavioural compensation
      strategies. Therefore, understanding the impact of task-dependent cortical
      activation patterns in non-invasive methods requires not only information derived
      from longitudinal studies pertaining to functional outcomes, but also a better
      understanding of what is kinematically learned during the acquisition of new
      skills.

PMID- 15502273
TI  - Impairment-oriented training (IOT)--scientific concept and evidence-based
      treatment strategies.
AB  - Everyday activities can be affected by many different body dysfunctions
      (impairments). A multi-modal analysis of electric brain activity revealed that
      movement-related brain activity is differentially altered in patients with
      different impairments, i.e. paresis, somatosensory deficits, and apraxia. Each
      body dysfunction has its own characteristics in terms of the resulting
      sensorimotor control deficits. The Impairment-oriented Training concept intends
      to characterise the resulting sensorimotor control deficits for each impairment.
      Based on such analyses two specific training techniques have been developed for
      stroke patients with mild and severe arm paresis: (1.) The Arm Ability training
      for mild arm paresis trains different sensorimotor abilities such as dexterity,
      speed of isolated hand and finger movements, steadiness, aiming, or tracking
      under visual guidance. Improvement of these motor abilities leads to improved
      motor performance in every day life circumstances. (2.) The Arm BASI S training
      for severe arm paresis intends to restore more basic motor control, i.e. the full
      range of active non-segmented motion of all limb segments, both postural
      activities and dynamic motion control, interjoint-coordination, and adequate
      motor control when external forces are applied. Clinical trials with
      representative study populations supported both techniques' clinical efficacy.

PMID- 15502274
TI  - Coupled rehabilitation protocols and neural plasticity: upper extremity
      improvements in chronic hemiparesis.
AB  - Identifying effective rehabilitation interventions founded on sound theoretical
      and neurophysiological bases should decrease the prevalence of motor disabilities
      and chronic hemiparesis. This article addresses two theoretically sound
      behavioral interventions: (a) active neuromuscular stimulation on the impaired
      upper extremity and (b) coupled bilateral coordination training (i.e., mirrored
      movements on the less impaired limb combined with active stimulation on the
      impaired limb). The series of stroke motor recovery experiments currently
      reviewed clearly indicate that sensorimotor integration theory and bimanual
      coordination theory are viable candidates for directing behavioral rehabilitation
      approaches. Indeed, the reported evidence clearly supports activity dependent
      neural plasticity for progress toward stroke motor recovery.

PMID- 15502275
TI  - Interactive robots for neuro-rehabilitation.
AB  - This article reviews a decade of work aimed at developing effective interactive
      robotic tools to treat and understand motor impairment and disability. The
      success of an initial pilot study with acute-phase in-patients recovering from
      stroke prompted a larger study showing that these results could be replicated and
      a follow-up study showing that the benefits lasted. Studies of chronic-phase out
      patients demonstrated that similar benefits could be obtained which also lasted
      and were accompanied by a concomitant reduction of pain. Exploration of the
      likely biology of recovery suggested an improvement of robotic treatment in the
      form of performance-based progressive therapy aimed at accelerating a process
      akin to motor learning postulated to underlie recovery. Initial studies of this
      method show a dramatic improvement over the previous successes. Kinematic studies
      of the recovery process show that, similar to the development of motor behavior
      in infants, it begins with stereotyped submovements and proceeds by progressively
      merging these to approach unimpaired motor performance.

PMID- 15502276
TI  - Recovery of gait and other motor functions after stroke: novel physical and
      pharmacological treatment strategies.
AB  - The gait-lab at Klinik Berlin developed and evaluated novel physical and
      pharmacological strategies promoting the repetitive practise of hemiparetic gait
      in line with the slogan: who wants to relearn walking, has to walk. Areas of
      research are treadmill training with partial body weight support, enabling
      wheelchair-bound subjects to repetitively practice gait, the electromechanical
      gait trainer GT I reducing the effort on the therapists as compared to the
      manually assisted locomotor therapy, and the future HapticWalker which will allow
      the additional practise of stair climbing up and down and of perturbations.
      Further means to promote gait practice after stroke was the application of
      botulinum toxin A for the treatment of lower limb spasticity and the early use of
      walking aids. New areas of research are also the study of D-Amphetamine, which
      failed to promote motor recovery in acute stroke patients as compared to placebo,
      and the development of a computerized arm trainer, Bi-Manu-T rack, for the
      bilateral treatment of patients with a severe upper limb paresis.

PMID- 15502277
TI  - Development and application of virtual reality technology to improve hand use and
      gait of individuals post-stroke.
AB  - Development and application of virtual reality (VR) systems for rehabilitation is
      an iterative process produced by collaboration of an inter-disciplinary team of
      engineers, neuroscientists and clinician-scientists. In this paper the use of
      virtual reality technology for the rehabilitation of individuals post-stroke is
      described. The development of the hardware is based on principles of motor
      control. Development of the software uses findings from the enrichment and motor
      plasticity and training literatures as well as principles of motor learning.
      Virtual environments are created to afford individuals post-stroke opportunities
      to practice tasks for which they require rehabilitation. These tasks, related to
      hand function and gait, are trained both at the impairment and functional level.
      The training engages users to allow for the repetitive intensive practice
      required for behavioral motor plasticity. Results from a series of upper and
      lower extremity studies indicate that use of VR technology to augment
      rehabilitation of individuals post-stroke merits further study.

PMID- 15502278
TI  - Neuromodulation paired with learning dependent practice to enhance post stroke
      recovery?
AB  - Over the past two decades, experimental studies following brain injury have shown
      that the central nervous system is dynamic and malleable to internal and external
      inputs. Neuromodulation and/or direct manipulation of motor and sensory
      experience can modify brain plasticity and functional outcome after experimental
      lesions. Specifically, pharmacologic modulation has been found to facilitate
      recovery of various behavioral deficits following occlusive injury. Additionally,
      the behavioral experience that induces long-term plasticity in motor and sensory
      maps after injury appears to be limited to those that entail the development of
      new skills. These data have strong application to human rehabilitation. This
      review will: (1) overview critical experimental studies that show that
      pharmacologic manipulation and/or specific behavioral experience may modify the
      functional organization of the injured brain and (2) review beginning studies
      which are exploring the application of this knowledge clinically.

PMID- 15502279
TI  - Advances in adjuvant pharmacotherapy for motor rehabilitation: effects of
      levodopa.
AB  - Hemiparesis is common after stroke and often severely disabling. Until very
      recently, the only therapeutic option for motor recovery was physiotherapeutic
      training. Experimental animal studies have shown that when applied in addition to
      exercises pharmacological interventions that affect the norepinephrine system can
      enhance the rate of functional motor recovery. These effects were observed when
      an increase in norepinephrine concentration in the CNS was pharmacologically
      induced. We recently showed that 3 weeks of single daily doses of 100 mg L-dopa,
      which is metabolized into norepinephrine in the brain, increase the efficacy of
      physiotherapy in hemiparetic stroke patients. Two additional randomized
      controlled trials with stroke patients also demonstrated the clinical relevance
      of this approach for motor recovery and independence in activities of daily
      living. Modifying effects of other frequently occurring clinical symptoms such as
      spasticity, neglect, and attention were also investigated. Thus, in view of its
      minimal side effects, L-dopa can be recommended in conjunction with exercise
      therapy to improve the functional outcome in stroke rehabilitation.

PMID- 15502280
TI  - Spot check and recalibration of stabilometric platforms.
AB  - The purpose of this paper is to describe a system for the rapid spot check of the
      accuracy of stabilometric platforms used in clinical posturography and, if
      needed, for estimating a recalibration matrix. It is based on a simple mechanical
      device which can be applied to any stabilometric platform; it consists of a
      ballast and a rotating mass which can generate a spiral-shaped training set of
      posturographic data. A software package has been developed whose purpose is to
      estimate a calibration matrix and to provide a figure of merit for the calibrated
      system. The data analysis is organized into two phases: a preliminary global
      phase, which uses the covariance matrix of the training set, and a refinement,
      iterative phase, which exploits the equation of the spiral. The characteristic
      features of the proposed system are: 1) it uses dynamic, not static loading, 2)
      loading is not applied manually, 3) it uses distributed, not point loads, 4)
      there is no need to bolt the system to the platform. Although these features are
      found, separately, in different prototypes described in the literature, their
      combination can only be found in the proposed system. Moreover, while most
      systems in the literature are intended for gait analysis, the proposed one is
      specifically designed for posturography.

PMID- 15502281
TI  - Remeshed smoothed particle hydrodynamics simulation of the mechanical behavior of
      human organs.
AB  - In computer aided surgery the accurate simulation of the mechanical behavior of
      human organs is essential for the development of surgical simulators. In this
      paper we introduce particle based simulations of two different human organ
      materials modeled as linear viscoelastic solids. The constitutive equations for
      the material behavior are discretized using a particle approach based on the
      Smoothed Particle Hydrodynamics (SPH) method while the body surface is tracked
      using level sets. A key aspect of this approach is its flexibility which allows
      the simulation of complex time varying topologies with large deformations. The
      accuracy of the original formulation is significantly enhanced by using a
      particle reinitialization technique resulting in remeshed Smoothed Particle
      Hydrodynamics (rSPH). The mechanical parameters of the systems used in the
      simulations are derived from experimental measurements on human cadaver organs.
      We compare the mechanical behavior of liver- and kidney-like materials based on
      the dynamic simulations of a tensile test case. Moreover, we present a particle
      based reconstruction of the liver topology and its strain distribution under a
      small local load. Finally, we demonstrate a unified formulation of fluid
      structure interaction based on particle methods.

PMID- 15502282
TI  - Optimal femoral head contour segmentation in CT images using dynamic programming.
AB  - We present a new contour segmentation method for femoral head detection in CT
      images. The principal idea underlying our approach is to represent the contour
      using active rays. Each ray has internal energy (continuity and smoothness
      constraints), as well as external energy (image-oriented edges and global a
      priori knowledge). The causal nature of this representation allows a globally
      optimal, non-iterative solution to be found using dynamic programming. Moreover,
      even pathological bone structures can be automatically segmented. Several
      clinical situations on pelvis CT scan with hip degenerative change shows that
      this approach is more efficient than conventional methods. In this paper, we
      describe our method and discuss how it can be used to create graphical 3D models
      of the hip that are suitable for preoperative planning.

PMID- 15502283
TI  - An improved bioacoustic method for monitoring of respiration.
AB  - Reliable monitoring of respiration plays an important role in a broad spectrum of
      applications. Today, there are several methods for monitoring respiration, but
      none of them has proved to be satisfactory in all respects. We have recently
      developed a bioacoustic method that can accurately time respiration from tracheal
      sounds. The aim of this study is to tailor this bioacoustic method for monitoring
      purposes by introducing dedicated signal processing. The method was developed on
      a material of ten patients and then tested in another ten patients treated in an
      intensive care unit. By studying the differences in the variation of the spectral
      content between the different phases of respiration, the described method can
      distinguish between inspiration and expiration and can extract respiration
      frequency, and respiration pause periods. The system detected 98% of the
      inspirations and 99% of the expirations. This method for respiration monitoring
      has the advantage of being simple, robust and the sensor does not need to be
      placed closed to the face. A commercial heart microphone was used and we
      anticipate that further improvement in performance can be achieved trough
      optimization of sensor design.

PMID- 15502284
TI  - Effect of strain rate on tensile properties of sheep disc anulus fibrosus.
AB  - We investigated the effect of loading rate on tensile properties of sheep bone
      anulus-bone specimens in axial direction. Disc anulus Samples with adjacent bone
      attachments were prepared from lateral, posterior and anterior regions of sheep
      lumbar spinal segments. The specimens were then tested at different strain rates
      under non-destructive cyclic tensile loading followed by destructive tensile
      loading. Each specimen was prepared by embedding the bony parts in the
      polymethylmetacrylate (PMMA) exposing the anulus portion to support tension. The
      results of non-destructive cyclic tests indicated a decrease in the hysteresis
      energy loss as strain rate increased. In the destructive tests, no significant
      differences in ultimate stress, ultimate strain and strain energy density were
      observed at different strain rates or annulus locations. However, there was a
      significant increase in the modulus at linear region as strain rate increased.
      Two major modes of failure were observed; rupture in the anulus mid-substance and
      at the anulus-endplate junction. The former failure was more frequent with no
      clear pattern across strain rates and locations, while the latter failure at
      anulus-endplate junction occurred primarily at slow strain rates.

PMID- 15502285
TI  - Rectal atresia, choanal atresia and congenital heart disease: a rare association.
AB  - Rectal atresia is an extremely rare anorectal malformation. A unique case of
      rectal atresia presenting as an imperforate membrane associated with congenital
      cardiac malformations and unilateral choanal atresia in a newborn is reported.
      Ultrasound examination in the newborn infant located the presence of the rectal
      membrane which was surgically treated successfully.

PMID- 15502286
TI  - Patient Record Information System (PaRIS) for primary health care centers in
      Indonesia.
AB  - This study explores the Patient Record Information System (PaRIS) for primary
      health care centers in a developing country such as Indonesia. The specific
      geography of the thousand islands country Indonesia is the reason for
      transportation difficulties as well as communication problems. This causes a
      serious adverse effect on the public healthcare service especially in the rural
      area within the country. Hence, a sustainable system is required that makes use
      of appropriate Information and Communication Technology (ICT). We developed a
      clinical information system with modest communication technology combined with a
      unique database distribution system. The Internet and its free software are the
      main tools for this system. It is a good opportunity for a developing country
      such as Indonesia to apply open free software in regard to the healthcare sector.
      This cost effective and sustainable system can enhance the work of physicians in
      order to provide better and applicable public health care service.

PMID- 15502288
TI  - Upper extremity musculoskeletal symptoms and functional impairment associated
      with computer use among college students.
AB  - PURPOSE: Occupational computer use has been associated with upper extremity
      musculoskeletal disorders among working-age adults, but little is known about
      computer-related musculoskeletal problems among college students. We carried out
      a descriptive epidemiological study of computer use-associated symptoms,
      functional limitations, and medication and health care utilization in this
      population. SUBJECTS AND METHODS: Cross-sectional survey of 240 undergraduates in
      the second through fourth years at a residential dormitory at a four-year college
      with random housing assignments. RESULTS: 194 students returned useable surveys
      (81% response rate). 42% reported upper extremity pain or discomfort when using a
      computer in the preceding two weeks. 41% said this pain or discomfort caused
      functional limitation and 9% said that these symptoms hindered academic or
      extracurricular performance. 23% reported taking medications for upper extremity
      pain related to computing (4% regularly) and 16% had seen a health care provider
      for computer-related symptoms. Female students, students of racial/ethnic
      minority groups, and students who experienced symptoms with < or = 1 hour of
      computer use were more likely to report symptom-related functional limitation
      than others. CONCLUSION: College students report high rates of computer use
      associated upper extremity musculoskeletal symptoms and symptom-related
      functional limitation. Future studies should more closely examine exposure,
      demographic, and ergonomic correlates of these symptoms and outcomes.

PMID- 15502289
TI  - An online learning course in Ergonomics.
AB  - For the past two years, the Department of Occupational Therapy at the University
      of Haifa has offered an online course to third year occupational therapists on
      the topic of Ergonomics for Health Care Professionals. The development and
      implementation of this course was funded by the Israeli Ministry of Education.
      Unique teaching materials, developed and uploaded to the University's server via
      "High Learn", included interactive and self-directed documents containing
      graphics, animations, and video clips. Extensive use was made of the discussion
      forum and survey tools, and students submitted all assignments online. For the
      final topic, an expert in ergonomics from Boston University delivered a lecture
      via two-way videoconferencing. The course site included comprehensive library
      listings in which all bibliographic materials were made available online.
      Students accessed course materials at the University in a computer classroom and
      at home via modem. In an accompanying research study, the frequency of student
      usage of the various online tools was tracked and extensive data were collected
      via questionnaires documenting students' demographic background, preferred
      learning style, prior usage of technology, satisfaction with the course and
      academic achievement. This paper focuses on the results of the research study
      that examined how the students responded to and coped with teaching material
      presented and accessed in this format.

PMID- 15502290
TI  - The effectiveness of job specific training on the occupational performance of
      student nurses.
AB  - Body mechanic checklist scores during a one-person pivot transfer, and boosting
      up in bed were evaluated to determine the effectiveness of training on the work
      performance of female student nurses from a local college. Thirty subjects
      participated in the study and were divided into a control group, an experimental
      group that received basic body mechanic training, and an experimental group that
      received job specific training. A one-way ANCOVA was calculated to examine the
      effects of the experimental procedures on the subjects' performance. This
      revealed a statistically significant difference between the groups (patient
      transfer F = 10.11, p value < 0.001; boosting F = 38.62, p value < 0.001). A post
      hoc analysis (Bonferroni procedure) indicated that the job specific training
      group (mean 11.65, SD 0.66) demonstrated a statistically significant improvement
      in their performance compared to the other two groups (control group mean 7.5, SD
      0.67; BBMT mean 9.66, SD 0.67).

PMID- 15502291
TI  - Musculoskeletal symptom survey among cement and concrete workers.
AB  - Work in construction is associated with a high risk for musculoskeletal disorders
      and injuries. The symptom survey was conducted to determine the magnitude and
      musculoskeletal injury characteristics among the cement and concrete workers and
      identify the most problematic work-related activities and job factors that might
      have contributed to the occurrence of these disorders. Findings revealed that a
      large proportion of the laborers (77%) experienced at least one musculoskeletal
      disorder in the last year. Low back pain was reported as the most frequently
      experienced symptom (66%). 'Working while in pain' the concrete workers perceived
      as the major problem in the trade. Other problematic work-related activities
      included 'bending or twisting the back', 'work in hot, cold or wet conditions',
      and 'handling heavy objects'. Most of the laborers (82%) requested on-the-job
      safety training. Survey results combined with the outcomes of focus groups
      discussions and work site observations were used in the design of a training
      program aimed at the prevention of musculoskeletal morbidity in the trade. The
      program incorporated ergonomics principles, hazard recognition, safe work
      practices, problem solving and personal protection in the training curriculum for
      membership of the trade.

PMID- 15502292
TI  - Informed decision making on assistive technology workplace accommodations for
      people with visual impairments.
AB  - Underemployment of people with visual impairments is an important problem in the
      world of work. Barriers to successful employment include the lack of informed
      decision making concerning AT as a workplace accommodation. Choosing effective
      Assistive Technology (AT) as an accommodation solution is imperative to
      successful employment of individuals with vision impairments. While not all jobs
      require AT as a part of an accommodation, when AT is needed, an informed choice
      is the best approach. This article describes the five step process for selecting
      appropriate AT for individuals with vision impairments in workplace
      accommodations developed by the Job Accommodation Network (JAN). Cases from the
      JAN database that involve people with vision impairments were examined. Resources
      to enable readers to further evaluate and implement effective AT solutions are
      provided.

PMID- 15502293
TI  - A comprehensive work injury prevention program with clerical and office workers:
      Phase II.
AB  - Sixteen full-time clerical and office workers participated in this prospective
      parallel-randomized trial. Intervention consisted of four hours of individualized
      training through a multi-faceted injury prevention program. In Phase I,
      musculoskeletal symptoms, stress, and energy levels were measured before and
      after intervention. Differences between Group A (intervention) and Group B
      (control) were described; pre to post differences between members within each
      group were also described. In Phase II, there were a greater number of
      statistically and clinically relevant differences within Group A at week 16
      (eleven weeks following intervention) than at week five (immediately post
      intervention). The eyes, neck, shoulder, elbow-forearm, and wrist-hand were
      impacted most positively by intervention, however, the frequency and intensity of
      headaches increased. Stress and energy level differences were minimal. Group B
      workers received intervention during weeks 18-21. Differences in average measures
      from pre to immediately post-intervention were greater within Group B than Group
      A. Both groups reported fewer sick days during the month of intervention than
      during pre and post-intervention months.

PMID- 15502294
TI  - Approaches to worker rehabilitation by occupational and physical therapists in
      the United States: factors impacting practice.
AB  - Work-related rehabilitation services have changed in nature and scope since their
      inception in the late 1970s. A review of the literature reveals a large body of
      published data concerning the various approaches used by therapists in this
      practice area, but a limited number of comparison studies documenting the value
      of one approach over the other. This national survey of physical and occupational
      therapists in the US was conducted in 2002, and examined the prevailing trends in
      service provision, and factors that determine the nature of services provided to
      clients. Results indicate that services continue the move to onsite service
      provision and an emphasis on prevention, but that select services, such as onsite
      job analysis and comprehensive, inter-disciplinary programs are being used to a
      limited degree. Research that examines the relative contributions of selected
      work-related services to successful and efficient return to work outcomes is
      necessary to identify best practice approaches. Therapists and insurance
      providers should work more closely in exchange of data that will ensure optimal
      program design and funding.

PMID- 15502295
TI  - Work functioning: a conceptual framework.
AB  - Adequate and reliable methods for evaluation of clients with work disabilities
      are crucial for both the individuals who are assessed and for society as a whole.
      Sound and precise work assessments are needed to guide clients to suitable
      interventions using a minimum of rehabilitation resources. Occupational therapy
      literature contains evidence that work function assessments are complex and that
      there is confusion over work assessment concepts. Therefore, further development
      and evaluation of adequate concepts and theoretical models within the area of
      work assessment is needed. This article proposes a conceptual framework for
      different dimensions of work functioning and points out important factors for
      work assessment. The concepts proposed and defined in the article are: work
      functioning, work participation, work performance, and individual capacity.

PMID- 15502296
TI  - Prediction of future low levels of sickness absence among young persons sick
      listed with back, neck, or shoulder diagnoses.
AB  - In recent years sickness absence has increased in most Western countries. Risk
      factors for sickness absence and disability pension have been emphasised in
      studies, while focus on factors predicting low sickness absence is very rare.
      This paper is an attempt to apply such a perspective in an 11-year prospective
      cohort study of young persons n = 213) who in 1985 were sick listed > or = 28
      days with back, neck, or shoulder diagnoses. Having had no sick-leave spells > 14
      days in 1992-1996 was used as the outcome measure. Sixty-nine persons (34%) had
      no such spells, with an unexpected similar proportion of men and women. Data on
      prior sick leave and demographic variables were analysed using univariate and
      multiple logistic regression. Factors that predicted low sickness absence were
      having prior low sickness absence, being a white-collar worker, and being
      married. We concluded that individuals with a history of low sickness absence
      have an increased odds for remaining in the work force after a single long sick
      leave spell, and might need less attention in rehabilitation compared to persons
      with a history of high sickness absence. Focusing on low sickness absence led to
      different results than those discussed in previous studies on risk factors for
      disability pension.

PMID- 15502297
TI  - Loads on the lumbar spine during a work capacity assessment test.
AB  - Many clinicians and employers utilise work-related assessment tools for the
      purposes of identifying whether or not the performance of a specific job exposes
      an individual to a heightened risk of developing a low back injury. However,
      research has shown that some of these tools have not been assessed for validity
      or reliability, and thus may not accurately assess the risk associated with a
      particular activity. An example of a test employed by some Australian private
      industries is the Work Capacity Assessment Test, which is a procedure that is
      commonly used to screen potential employees and evaluate those workers returning
      to the workplace following injury. This research was designed to simulate the
      lifting component of the Work Capacity Assessment Test and involved a series of
      lifts ranging from 2.5 kg to 22.5 kg. Six subjects performed this task, whilst
      being assessed using two-dimensional videography and surface electromyography.
      The two-dimensional kinematic data were input into the 4D WATBAK software to
      quantify the compression forces acting between L4 and L5 during each performance.
      Results of this study showed that spinal compression and paraspinal muscle
      activity increased incrementally from the 2.5 kg lift to the 22.5 kg lift, whilst
      abdominal muscle activity also increased across the lifts. This study
      demonstrated that lifting masses of 22.5 kg or more can produce loads on the
      spine that are considered potentially hazardous, when compared to safe lifting
      guidelines, and indicated that there is a clear concern for the use of such
      lifting tasks in the evaluation of workers following injury.

PMID- 15502298
TI  - Structure of human erythrocyte NADH-cytochrome b5 reductase.
AB  - Erythrocyte NADH-cytochrome b(5) reductase reduces methaemoglobin to functional
      haemoglobin. In order to examine the function of the enzyme, the structure of
      NADH-cytochrome b(5) reductase from human erythrocytes has been determined and
      refined by X-ray crystallography. At 1.75 A resolution, the root-mean-square
      deviations (r.m.s.d.) from standard bond lengths and angles are 0.006 A and 1.03
      degrees , respectively. The molecular structure was compared with those of rat
      NADH-cytochrome b(5) reductase and corn nitrate reductase. The human reductase
      resembles the rat reductase in overall structure as well as in many side chains.
      Nevertheless, there is a large main-chain shift from the human reductase to the
      rat reductase or the corn reductase caused by a single-residue replacement from
      proline to threonine. A model of the complex between cytochrome b(5) and the
      human reductase has been built and compared with that of the haem-containing
      domain of the nitrate reductase molecule. The interaction between cytochrome b(5)
      and the human reductase differs from that of the nitrate reductase because of
      differences in the amino-acid sequences. The structures around 15 mutation sites
      of the human reductase have been examined for the influence of residue
      substitutions using the program ROTAMER. Five mutations in the FAD-binding domain
      seem to be related to cytochrome b(5).

PMID- 15502299
TI  - Recurring main-chain anion-binding motifs in short polypeptides: nests.
AB  - A novel tripeptide motif called a nest has recently been described in proteins
      with the function of binding anionic, or partially anionic, atoms such as
      carbonyl O atoms. In the present work, a search for nests in small polypeptides
      stored in the Cambridge Structural Database is reported. 37 unique examples were
      found: over half form part of hydrogen-bond arrangements resembling those in
      proteins, such as Schellman/paperclip loop motifs, various types of beta-turn and
      Asx-turns or Ser/Thr-turns, while a third are in novel situations, some involving
      binding to anionic groups from other molecules within the crystal complex. An
      example is the antibiotic vancomycin, which incorporates a prominent nest forming
      part of a peptide-binding site. This nest binds the carboxylate of the C-terminal
      D-alanine of the bacterial cell-wall precursor peptide, thereby inhibiting the
      final step of bacterial cell-wall synthesis. As in proteins, a number of nests
      occur in short peptides with an alternating glycine/L-amino-acid sequence but,
      uniquely to non-ribosomally synthesized short peptides, several nests within them
      are constructed from alternating D- and L-amino acids, and such sequences seem to
      specially favour nests.

PMID- 15502300
TI  - Inhibitor binding at the protein interface in crystals of a HIV-1 protease
      complex.
AB  - Depending on the excess of ligand used for complex formation, the HIV-1 protease
      complexed with a novel phenylnorstatine inhibitor forms crystals of either
      hexagonal (P6(1)) or orthorhombic (P2(1)2(1)2(1)) symmetry. The orthorhombic form
      shows an unusual complexity of crystal packing: in addition to one inhibitor
      molecule that is bound to the enzyme active site, the second inhibitor molecule
      is bound as an outer ligand at the protein interface. Binding of the outer ligand
      apparently increases the crystal-quality parameters so that the diffraction data
      allow solution of the structure of the complex at 1.03 A, the best resolution
      reported to date. The outer ligand interacts with all four surrounding HIV-1
      protease molecules and has a bent conformation owing to its accommodation in the
      intermolecular space. The parameters of the solved structures of the orthorhombic
      and hexagonal forms are compared.

PMID- 15502302
TI  - Radiation-damage-induced phasing with anomalous scattering: substructure solution
      and phasing.
AB  - Substructure-solution and phasing procedures using a combination of anomalous
      scattering and radiation-damage-induced isomorphous differences have been
      investigated. The tyrosine residues in thaumatin were iodinated with N
      iodosuccinimide in the crystalline form as well as prior to crystallization.
      Several data sets were collected from both forms and used for substructure
      solution and phasing using various protocols, employing anomalous, isomorphous or
      both these signals. It was shown that combination of the anomalous and
      isomorphous signals in the form of the RIPAS (radiation-damage-induced phasing
      with anomalous scattering) strategy is beneficial for both locating the
      substructure and subsequent phasing.

PMID- 15502301
TI  - Structure of 2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase from Shewanella
      oneidensis at 1.6 A: identification of farnesyl pyrophosphate trapped in a
      hydrophobic cavity.
AB  - Isopentenyl pyrophosphate (IPP) is a universal building block for the ubiquitous
      isoprenoids that are essential to all organisms. The enzymes of the non
      mevalonate pathway for IPP synthesis, which is unique to many pathogenic
      bacteria, have recently been explored as targets for antibiotic development.
      Several crystal structures of 2C-methyl-D-erythritol-2,4-cyclophosphate (MECDP)
      synthase, the fifth of seven enzymes involved in the non-mevalonate pathway for
      synthesis of IPP, have been reported; however, the composition of metal ions in
      the active site and the presence of a hydrophobic cavity along the non
      crystallographic threefold symmetry axis has varied between the reported
      structures. Here, the structure of MEDCP from Shewanella oneidensis MR1 (SO3437)
      was determined to 1.6 A resolution in the absence of substrate. The presence of a
      zinc ion in the active-site cleft, tetrahedrally coordinated by two histidine
      side chains, an aspartic acid side chain and an ambiguous fourth ligand, was
      confirmed by zinc anomalous diffraction. Based on analysis of anomalous
      diffraction data and typical metal-to-ligand bond lengths, it was concluded that
      an octahedral sodium ion was 3.94 A from the zinc ion. A hydrophobic cavity was
      observed along the threefold non-crystallographic symmetry axis, filled by a well
      defined non-protein electron density that could be modeled as farnesyl
      pyrophosphate (FPP), a downstream product of IPP, suggesting a possible feedback
      mechanism for enzyme regulation. The high-resolution data clarified the FPP
      binding mode compared with previously reported structures. Multiple sequence
      alignment indicated that the residues critical to the formation of the
      hydrophobic cavity and for coordinating the pyrophosphate group of FPP are
      present in the majority of MEDCP synthase enzymes, supporting the idea of a
      specialized biological function related to FPP binding in a subfamily of MEDCP
      synthase homologs.

PMID- 15502303
TI  - Structure determination and refinement at 2.44 A resolution of argininosuccinate
      lyase from Escherichia coli.
AB  - Escherichia coli argininosuccinate lyase has been crystallized from a highly
      concentrated sample of purified recombinant alpha-methylacyl-CoA racemase, in
      which it occurred as a minor impurity. The structure has been solved using
      molecular replacement at 2.44 A resolution. The enzyme is tetrameric, but in this
      crystal form there is a dimer in the asymmetric unit. The tetramer has four
      active sites; each active site is constructed from loops of three different
      subunits. One of these catalytic loops, near residues Ser277 and Ser278, was
      disordered in previous structures of active lyases, but is very well ordered in
      this structure in one of the subunits owing to the presence of two phosphate ions
      in the active-site cavity. The positions of these phosphate ions indicate a
      plausible mode of binding of the succinate moiety of the substrate in the
      competent catalytic complex.

PMID- 15502304
TI  - Solution and structure of an alternating D,L-peptide.
AB  - The crystal structure of H-(L-Tyr-D-Tyr)(4)-L-Lys-OH has been determined to 1.3 A
      resolution. The D,L-alternating peptide crystallizes in the tetragonal system,
      space group P4(3)2(1)2, with unit-cell parameters a = b = 27.99 (3), c = 78.93
      (8) A. The crystals contain two molecules in the asymmetric unit that form a
      double-stranded right-handed antiparallel beta-helix. The structure has been
      solved by SIRAS using a crystal soaked in an iodide-containing solution for 1
      min. The programs SHELXD and SHELXE were used to determine the iodide
      substructure and also the experimental electron-density map. Using the
      coordinates of known D,L-peptides deposited in the PDB, several attempts were
      made to solve the structure by molecular-replacement techniques. Although the
      backbone of the MR model selected shows great similarity and was used to trace
      the actual peptide structure in the map, it was not possible to obtain the
      correct solution before the experimental phases became available. The correct
      fragment orientations are easily determined, but the same does not apply to the
      translation search. Nevertheless, insights into fragment search and expansion
      were gained from the tests described in this paper. The correlation coefficient
      calculated with the resolution shell of data around 2.4 A, a distance
      corresponding to most 1-3 interatomic vectors, is a particularly good
      discriminator of correct orientations in the rotation search of small fragments.

PMID- 15502305
TI  - A pivotal role for reductive methylation in the de novo crystallization of a
      ternary complex composed of Yersinia pestis virulence factors YopN, SycN and
      YscB.
AB  - Structural studies of a ternary complex composed of the Yersina pestis virulence
      factors YopN, SycN and YscB were initially hampered by poor solubility of the
      individual proteins. Co-expression of all three proteins in Escherichia coli
      yielded a well behaved complex, but this sample proved to be recalcitrant to
      crystallization. As crystallization efforts remained fruitless, even after the
      proteolysis-guided engineering of a truncated YopN polypeptide, reductive
      methylation of lysine residues was employed to alter the surface properties of
      the complex. The methylated complex yielded crystals that diffracted X-rays to a
      maximal resolution of 1.8 A. The potential utility of reductive methylation as a
      remedial strategy for high-throughput structural biology was further underscored
      by the successful modification of a selenomethionine-substituted sample.

PMID- 15502306
TI  - Optimizing the error term in direct-method SAD phasing.
AB  - The probability formula of the direct-method SAD (single-wavelength anomalous
      diffraction) phasing proposed by Fan & Gu (1985, Acta Cryst. A41, 280-284)
      contains an error term which is related to the lack-of-closure error. This error
      term is used as a weighting function in the phase derivation and in the
      subsequent calculation of electron-density maps. Previously, there has been a
      constant in the error term that has had to be determined empirically for each
      particular case. It has been found that improper choice of the constant often
      leads to failure of the direct-method SAD phasing. The problem is resolved by
      introducing a modified error term and a method of automatically tuning the
      associated scaling factor.

PMID- 15502307
TI  - Direct-method SAD phasing with partial-structure iteration: towards automation.
AB  - The probability formula of direct-method SAD (single-wavelength anomalous
      diffraction) phasing proposed by Fan & Gu (1985, Acta Cryst. A41, 280-284)
      contains partial-structure information in the form of a Sim-weighting term.
      Previously, only the substructure of anomalous scatterers has been included in
      this term. In the case that the subsequent density modification and model
      building yields only structure fragments, which do not straightforwardly lead to
      the complete solution, the partial structure can be fed back into the Sim
      weighting term of the probability formula in order to strengthen its phasing
      power and to benefit the subsequent automatic model building. The procedure has
      been tested with experimental SAD data from two known proteins with copper and
      sulfur as the anomalous scatterers.

PMID- 15502308
TI  - Structure of the RNA-processing inhibitor RraA from Thermus thermophilis.
AB  - The menG gene product, thought to catalyze the final methylation in vitamin K(2)
      synthesis, has recently been shown to inhibit RNase E in Eschericha coli. The
      structure of the protein, since renamed RraA, has been solved to 2.3 A using the
      multiple-wavelength anomalous diffraction method and selenomethionine-substituted
      protein from Thermus thermophilus. The six molecules in the asymmetric unit are
      arranged as two similar trimers which have a degree of interaction, suggesting
      biological significance. The fold does not support the postulated methylation
      function. Genomic analysis, specifically a lack of an RNase E homologue in cases
      where homologues to RraA exist, indicates that the function is still obscure.

PMID- 15502309
TI  - Crystallization and preliminary X-ray crystallographic analysis of chorismate
      synthase from Mycobacterium tuberculosis.
AB  - The enzymes of the shikimate pathway are potential targets for the development of
      new therapies because they are essential for bacteria but absent from mammals.
      The last step in this pathway is performed by chorismate synthase (CS), which
      catalyzes the conversion of 5-enolpyruvylshikimate-3-phosphate to chorismate.
      Optimization of crystallization trials allowed the crystallization of homogeneous
      recombinant CS from Mycobacterium tuberculosis (MtCS). The crystals of MtCS
      belong to space group P6(4)22 (or P6(2)22) and diffract to 2.8 A resolution, with
      unit-cell parameters a = b = 129.7, c = 156.8 A. There are two molecules in the
      asymmetric unit. Molecular-replacement trials were not successful. Heavy-atom
      derivative screening is in progress.

PMID- 15502310
TI  - Crystallization and preliminary X-ray diffraction analysis of homing endonuclease
      I-Tsp061I.
AB  - Two crystal forms, rhombohedral and hexagonal, of a homing endonuclease from
      Thermoproteus sp. IC-061 (I-Tsp0611) were obtained by the hanging-drop and
      sitting-drop method, respectively. The hexagonal crystals belong to space group
      P6(3)22, with unit-cell parameters a = b = 111.4, c = 97.6 A, and diffract to 3.2
      A resolution on beamline BL44 at SPring-8 (Harima, Japan). The rhombohedral
      crystals belong to space group R32, with unit-cell parameters a = b = 95.4, c =
      192.9 A, and diffract to 2.7 A resolution using a Cu Kalpha rotating-anode
      generator with an R-AXIS VII detector. The crystal asymmetric unit contained one
      protein molecule and the solvent contents of the two crystal forms were estimated
      to be 68.3 and 67.6% by volume, respectively.

PMID- 15502311
TI  - Cloning, expression, purification, crystallization and preliminary X-ray
      characterization of the full-length single-stranded DNA-binding protein from the
      hyperthermophilic bacterium Aquifex aeolicus.
AB  - Single-stranded DNA-binding (SSB) proteins stabilize single-stranded DNA, which
      is exposed by separation of the duplex during DNA replication, recombination and
      repair. The SSB protein from the hyperthermophile Aquifex aeolicus has been
      overexpressed in Escherichia coli, purified and characterized and crystals of the
      full-length protein (147 amino acids; M(r) 17 131.20) have been grown by vapour
      diffusion from ammonium sulfate pH 7.5 in both the absence and presence of ssDNA
      [dT(pT)(68)]. All crystals diffract to around 2.9 A resolution and those without
      bound DNA (native) belong to space group P2(1), with two tetramers in the
      asymmetric unit and unit-cell parameters a = 80.97, b = 73.40, c = 109.76 A, beta
      = 95.11 degrees . Crystals containing DNA have unit-cell parameters a = 108.65, b
      = 108.51, c = 113.24 A and could belong to three closely related space groups
      (I222, I2(1)2(1)2(1) or I4(1)) with one tetramer in the asymmetric unit.
      Electrospray mass spectrometry of the crystals confirmed that the protein was
      intact. Molecular replacement with a truncated E. coli SSB structure has revealed
      the position of the molecules in the unit cell and refinement of both native and
      DNA-bound forms is under way.

PMID- 15502312
TI  - Crystallization and preliminary crystallographic analysis of the fusion core of
      the spike protein of the murine coronavirus mouse hepatitis virus (MHV).
AB  - Crystals of a 2-Helix fusion-core construct of MHV spike protein (commonly
      referred to as E2) have been grown at 291 K using PEG 4000 as precipitant. The
      diffraction pattern of the crystal extends to 2.8 A resolution at 100 K in-house.
      Furthermore, a selenomethionine (SeMet) derivative of MHV spike protein fusion
      core has been overexpressed and purified. The derivative crystals were obtained
      under similar conditions and three different wavelength data sets were collected
      to 2.4 A resolution from a single derivative crystal at BSRF (Beijing Synchrotron
      Radiation Facility). The crystals have unit-cell parameters a = b = 48.3, c =
      199.6 A, alpha = beta = 90, gamma = 120 degrees and belong to space group R3.
      Assuming the presence of two molecules in the asymmetric unit, the solvent
      content is calculated to be about 46%.

PMID- 15502313
TI  - Crystallization and preliminary X-ray crystallographic analysis of chitinase F1
      (ChiF1) from the alkaliphilic Nocardiopsis sp. strain F96.
AB  - Chitinase F1 (ChiF1) isolated from the alkaliphilic Nocardiopsis sp. strain F96
      is a family 18 chitinase that hydrolyzes chitin, an insoluble beta-1,4-linked
      polymer of N-acetylglucosamine. Crystals of recombinant ChiF1 with molecular
      weight of 33 000 Da were grown to a suitable size for X-ray structure analysis
      using 18%(w/v) polyethylene glycol 8000, 200 mM zinc acetate dehydrate and 100 mM
      sodium cacodylate buffer pH 6.5. Diffraction data were collected at SPring-8 and
      show that the crystals belong to the trigonal space group P3(1)12 or P3(2)12,
      with unit-cell parameters a = 56.0, c = 179.5 A, and diffract X-rays beyond 1.2 A
      resolution. Crystallographic analysis was carried out using the multiwavelength
      anomalous diffraction (MAD) method using zinc as the anomalous scatter. The
      binding of Zn atoms was clarified from the Bijvoet and dispersive Patterson
      functions, which gave prominent zinc-zinc self-vectors on the Harker section.

PMID- 15502314
TI  - Expression, purification, crystallization and preliminary X-ray diffraction
      studies of human liver regucalcin.
AB  - Regucalcin is a novel calcium ion (Ca(2+)) binding protein that does not contain
      an EF-hand motif as a Ca(2+)-binding domain and has been demonstrated to play a
      multi-functional role in many cell types. Human liver regucalcin, consisting of
      299 amino-acid residues, was overexpressed in Escherichia coli, purified and
      crystallized by the vapour-diffusion method in the presence of polyethylene
      glycol 4000 as a precipitant. A native crystal diffracted to 2.8 A with
      synchrotron radiation and belongs to space group P2(1), with unit-cell parameters
      a = 64.87, b = 52.52, c = 86.38 A, beta = 99.86 degrees . Two molecules most
      probably exist in the asymmetric unit, corresponding to V(M) = 2.2 A(3) Da(-1).
      Heavy-atom derivative data were collected and the Pb derivative showed one high
      occupancy site per molecule.

PMID- 15502316
TI  - Crystallization and preliminary diffraction studies of TraF, a component of the
      Escherichia coli type IV secretory system.
AB  - TraF, a component of the Escherichia coli type IV secretory system, has been
      crystallized and preliminary X-ray diffraction data have been collected. TraF is
      a 26 kDa protein encoded by the E. coli F plasmid and is required for conjugative
      plasmid transfer and the formation of sex pili. The N-terminal domain of TraF has
      no recognizable sequence features, whereas the C-terminal domain is believed to
      adopt a thioredoxin fold. However, since the active-site cysteines of thioredoxin
      like proteins are not conserved in TraF, its biochemical role remains unclear.
      TraF crystallizes in space group C2, with unit-cell parameters a = 119.87, b =
      34.36, c = 46.21 A, beta = 90.40 degrees , and crystals diffract to 2.3 A
      resolution.

PMID- 15502315
TI  - Crystallization and preliminary X-ray analysis of VCBP3 from Branchiostoma
      floridae.
AB  - VCBPs represent a family of proteins with highly diversified immunoglobulin-like
      variable regions in species thought to lack an adaptive immune system. These
      proteins are expected to reveal important structural and functional features that
      could be highly informative in projecting the evolutionary history of the
      adaptive immune response. Preliminary X-ray diffraction data from amphioxus
      (Branchiostoma floridae) VCBP3 crystals were collected to 2.4 A resolution and
      reduced to primitive trigonal space groups P3(1(2))21. Unit-cell parameters are a
      = b = 58.99, c = 79.21 A, alpha = beta = 90, gamma = 120 degrees . Two distinct
      crystallization conditions yielded crystals with similar morphologies and these
      crystals are isomorphous to each other.

PMID- 15502317
TI  - Purification, crystallization and preliminary crystallographic studies of the
      ligand-binding domain of a plant vacuolar sorting receptor.
AB  - Vacuolar sorting receptor (VSR) proteins bind soluble protein ligands in a
      sequence-specific manner and target them to the lytic vacuole in plant cells. A
      VSR from Arabidopsis thaliana, AtBP80b, has been successfully purified after
      heterologous expression in Drosophila S2 cells. The AtBP80b protein (560 amino
      acids) was crystallized by the hanging-drop method with a PEG 400-based
      precipitant. Preliminary X-ray diffraction studies of an AtBP80b crystal showed
      that it belongs to the cubic space group P2(1)3 (or P4(2)32) and has unit-cell
      parameters a = b = c = 145.9 A. Crystals of the VSR diffract beyond 2.5 A
      resolution.

PMID- 15502318
TI  - Expression, purification and preliminary X-ray analysis of crystals of Bacillus
      subtilis glutamate racemase.
AB  - Glutamate racemase (MurI, RacE; E.C.5.1.1.3) catalyses the cofactor-independent
      conversion of L-glutamate to D-glutamate, an essential step in the synthesis of
      components of the bacterial cell wall. The gene for RacE from Bacillus subtilis
      has been cloned and the protein expressed in Escherichia coli, purified and
      crystallized in the presence of L-glutamate using the hanging-drop method of
      vapour diffusion with diammonium tartrate as the precipitant. The crystals belong
      to the monoclinic space group C2, with approximate unit-cell parameters a =
      133.6, b = 60.1, c = 126.2 A, beta = 117.6 degrees . Consideration of the
      possible values of V(M) suggests that the asymmetric unit contains either two
      (V(M) = 3.75 A(3) Da(-1)) or three (V(M) = 2.5 A(3) Da(-1)) subunits. The
      crystals diffract X-rays to at least 2.1 A resolution on a synchrotron-radiation
      source and are suitable for structural studies. Determination of the structure
      may provide insight into the molecular basis of substrate recognition and
      catalysis by this enzyme.

PMID- 15502319
TI  - Purification, characterization, crystallization and preliminary X-ray
      crystallographic analysis of two novel C-type lectin-like proteins: Aall-A and
      Aall-B from Deinagkistrodon acutus venom.
AB  - Aall-A and Aall-B, two novel heterodimeric snake-venom C-type lectin-like
      proteins (sv-CLPs), were purified from the venom of Deinagkistrodon acutus from
      Anhui, China. Strikingly, both these proteins can localize on and congregate
      human erythrocytes, instead of aiming at the common targets of sv-CLPs such as
      platelet glycoproteins, von Willebrand factors, coagulant factors etc. The
      crystals of Aall-A belong to space group P2, with unit-cell parameters a = 105.2,
      b = 56.2, c = 108.7 A, beta = 100.5 degrees , and diffract to 2.0 A resolution,
      while the crystals of Aall-B belong to space group P2(1)2(1)2(1), with unit-cell
      parameters a = 36.8, b = 56.5, c = 149.2 A, and diffract to 2.2 A resolution. To
      our knowledge, this is the first report of sv-CLPs with this unique function and
      of their preliminary crystallographic analysis.

PMID- 15502320
TI  - Crystallization and preliminary X-ray crystallographic studies of a lectin from
      the mushroom Marasmius oreades.
AB  - The Marasmius oreades agglutinin (MOA) recognizes blood group B oligosaccharides.
      This mushroom lectin belongs to the ricin superfamily and is currently the only
      lectin known with exclusive specificity for Galalpha1,3Gal-structures, as occur
      in the subterminally fucosylated blood group B epitope
      Galalpha1,3(Fucalpha1,2)Galbeta1,4GlcNAc (MOA's preferred ligand) or without
      fucosylation in the xenotransplantation epitope. MOA has been co-crystallized
      with the linear blood group B trisaccharide Galalpha1,3Galbeta1,4GlcNAc using the
      hanging-drop vapour-diffusion technique at room temperature. MOA crystals were
      grown in the presence of ammonium formate and HEPES buffer. A 3.0 A data set has
      been collected. Preliminary analysis of the X-ray data is consistent with space
      group P3(1) or P3(2) and unit-cell parameters a = b = 105, c = 113 A, with two
      dimers per asymmetric unit.

PMID- 15502321
TI  - Expression, crystallization and preliminary structural analysis of the
      ectoplasmic region of apical membrane antigen 1 from Plasmodium vivax, a malaria
      vaccine candidate.
AB  - Apical membrane antigen 1 (AMA1), a type 1 transmembrane protein present in the
      microneme organelles of Plasmodium, is a leading malaria-vaccine candidate. The
      ectoplasmic region of AMA1 from P. vivax has been expressed in Pichia pastoris
      and crystallized in two different forms: an orthorhombic form (space group
      P2(1)2(1)2(1), unit-cell parameters a = 54.1, b = 76.1, c = 103.9 A) and a
      monoclinic form (space group C2, unit-cell parameters a = 150.0, b = 53.8, c =
      60.3 A, beta = 113.2 degrees ). Native data have been collected to 2.0 A
      resolution for the orthorhombic form and 1.8 A for the monoclinic form. A
      platinum derivative was prepared for the orthorhombic and monoclinic crystals
      using K(2)PtCl(4) and data were collected at several wavelengths to obtain phases
      by the MAD technique. A partial model has been built from the electron-density
      maps of both forms and refinement is in progress.

PMID- 15502322
TI  - Crystallization and preliminary analysis of a water-forming NADH oxidase from
      Lactobacillus sanfranciscensis.
AB  - Single crystals have been obtained of NADH oxidase (Nox), a flavoenzyme cloned
      from Lactobacillus sanfranciscensis. The enzyme catalyzes the oxidation of two
      equivalents of NAD(P)H and reduces one equivalent of oxygen to yield two
      equivalents of water, without releasing hydrogen peroxide after the reduction of
      the first equivalent of NAD(P)H. The enzyme crystallizes in space group
      P2(1)2(1)2(1), with unit-cell parameters a = 59.6, b = 92.6, c = 163.5 A. The
      crystals diffract to 1.85 A resolution using synchrotron radiation. Matthews
      coefficient calculations suggest the presence of two molecules per asymmetric
      unit (V(M) = 2.3 A(3) Da(-1), 45.5% solvent content), which has been confirmed by
      the molecular-replacement solution using a search molecule derived from NADH
      peroxidase (PDB code 1f8w).

PMID- 15502323
TI  - RARbeta ligand-binding domain bound to an SRC-1 co-activator peptide:
      purification, crystallization and preliminary X-ray diffraction analysis.
AB  - Retinoids have demonstrated therapeutic efficacy in the treatment of acute
      promyelocytic leukaemia and in the chemoprevention of a large number of cancers.
      As the cellular signalling pathway of retinoids can be transduced by the three
      retinoic acid receptor (RAR) isotypes alpha, beta and gamma, the side effects of
      these treatments induced efforts to generate isotype-selective ligands. Despite
      knowledge of the crystal structures of RARalpha and RARgamma ligand-binding
      domains (LBDs), the rational design of such ligands has been hampered by the
      absence of RARbeta LBD structural data. Here, a strategy used to express a large
      scale soluble fraction of the human RARbeta LBD suitable for biophysical analysis
      is reported, as well as a procedure for crystallizing it bound to a synthetic
      retinoid (TTNPB) with or without a co-activator peptide (SRC-1). Preliminary X
      ray analysis revealed that both complexes crystallized in the orthorhombic space
      group P2(1)2(1)2(1). The unit-cell parameters are a = 47.81, b = 58.52, c = 92.83
      A for the TTNPB-hRARbeta LBD crystal and a = 58.14, b = 84.07, c = 102.37 A when
      the SRC-1 peptide is also bound.

PMID- 15502324
TI  - Crystallization, data collection and phasing of infestin 4, a factor XIIa
      inhibitor.
AB  - Infestin is a protein from Triatoma infestans (kissing bug) composed of seven
      Kazal-type domains that is further processed to yield several serine protease
      inhibitors with varying specificities. Infestins 3 and 4 are the last two domains
      of the infestin gene and are found in vivo in the insect's anterior midgut. The
      last domain, infestin 4, has been cloned, expressed and purified. Here, the
      crystallization of infestin 4 using the sitting-drop vapour-diffusion method with
      PEG 8000 as precipitant is described. Crystals belong to the orthorhombic space
      group P2(1)2(1)2(1), with unit-cell parameters a = 25.89, b = 45.64, c = 57.41 A.
      X-ray diffraction data were collected to a maximum resolution of 1.8 A using a
      synchrotron-radiation source. Initial phases were calculated by molecular
      replacement using an edited rhodniin molecule as the search model. Structure
      refinement is in progress.

PMID- 15502325
TI  - Preparation, crystallization and preliminary X-ray analysis of a complex between
      the Plasmodium vivax sexual stage 25 kDa protein Pvs25 and a malaria transmission
      blocking antibody Fab fragment.
AB  - The Plasmodium vivax sexual stage 25 kDa protein Pvs25, located on the surface of
      the ookinete form of the parasite, is a vaccine candidate designed to elicit
      immunity that blocks the transmission of malaria by mosquitoes. The 2A8 murine
      monoclonal antibody directed against recombinant Pvs25 prevents the formation of
      P. vivax oocysts in mosquitoes fed in the laboratory. The complex between
      recombinant Pvs25 and the Fab fragment of 2A8 forms crystals that diffract X-rays
      to 3.5 A. Two native data sets, A and B, have been collected from crystals of the
      Pvs25-Fab complex. Both crystals belong to space group P2(1), with unit-cell
      parameters of a = 86.3, b = 61.7, c = 142.7 A, beta = 101.7 degrees for data set
      A and a = 86.8, b = 61.0, c = 149.3 A, beta = 104.3 degrees for data set B, and
      contain two complex molecules per asymmetric unit. Efforts are under way to
      reveal the structure of the Pvs25-Fab complex by molecular replacement. The three
      dimensional structure of the Pvs25-Fab complex will provide an understanding of
      the interaction between Pvs25 and the 2A8 antibody that inhibits ookinete
      development in the mosquito and should aid in the development of transmission
      blocking vaccines against P. vivax malaria.

PMID- 15502326
TI  - Purification, crystallization and preliminary X-ray analysis of mexicain.
AB  - Mexicain is a 23.7 kDa papain-like cysteine protease from the tropical plant
      Jacaratia mexicana. Extracted as a mix of proteases from the latex of the fruit,
      mexicain is isolated after cation-exchange chromatography as the most abundant
      product. The purified product inhibited with E-64 was crystallized by sitting
      drop vapour diffusion in the presence of ethanolamine. Cryoprotected crystals
      diffracted X-rays from a home source to 1.98 A and belong to the monoclinic space
      group P2(1), with unit-cell parameters a = 57.36, b = 90.45, c = 80.39 A, beta =
      92.64 degrees . The asymmetric unit contains four molecules of mexicain, with a
      corresponding crystal volume per protein weight (V(M)) of 2.24 A(3) Da(-1) and a
      solvent content of 45% by volume. A molecular-replacement model has been
      determined and refinement is in progress.

PMID- 15502328
TI  - Crystallization and atomic resolution X-ray diffraction of the catalytic domain
      of the large sialidase, nanI, from Clostridium perfringens.
AB  - Sialidases catalyse the removal of terminal sialic acids from a range of
      glycoproteins, glycolipids and oligosaccharides. They have been found in
      bacteria, viruses and parasites, where they play important roles in pathogenesis
      and/or microbial nutrition, and in mammalian cells, where they modulate cell
      surface glycosylation associated with a range of cellular activities. Clostridium
      perfringens, a causative agent of gas gangrene and peritonitis in humans,
      possesses three sialidases: nanH, nanI and nanJ, with molecular weights of 42, 77
      and 129 kDa, respectively. The two larger enzymes are secreted by the bacterium
      and are involved in the pathogenesis and nutrition of Clostridium. As part of a
      study to examine the structures of all three enzymes, crystallization of the 77
      kDa nanI isoenzyme was attempted. The expressed full-length protein was found to
      degrade easily; a stable 50 kDa catalytic domain was therefore subcloned. This
      domain was overexpressed in Escherichia coli and produced crystals belonging to
      space group P2(1)2(1)2(1), with unit-cell parameters a = 96.98, b = 69.41, c =
      72.69 A and one monomer per asymmetric unit. The crystals diffract to at least
      0.92 A. A molecular-replacement solution was obtained using the catalytic domain
      of the sialidase from the leech Macrobdella decora.

PMID- 15502327
TI  - Crystallization and preliminary X-ray analysis of pyridoxal 4-dehydrogenase, the
      second enzyme in degradation pathway I of pyridoxine.
AB  - Pyridoxal 4-dehydrogenase (PLDH; EC 1.1.107) is the second enzyme in the
      bacterial degradation pathway I of vitamin B(6), which catalyzes the oxidation of
      pyridoxal to 4-pyridoxolactone using NAD(+). PLDH from Microbacterium luteolum, a
      dimeric protein with a subunit molecular weight of 38 kDa, was crystallized at
      277 K in a drop solution comprising 15%(w/v) polyethylene glycol 4000, 0.15 M
      sodium acetate, 7.5 mM n-octyl-beta-D-glucoside and 0.075 M Tris-HCl pH 7.5 by
      the sitting-drop vapour-diffusion method. The crystals were monoclinic and
      belonged to space group C2, with unit-cell parameters a = 107.0, b = 56.7, c =
      130.2 A, beta = 103.6 degrees . Diffraction data were collected from a single
      crystal to 2.0 A.

PMID- 15502329
TI  - Crystallization and preliminary X-ray diffraction analysis of spermidine synthase
      from Helicobacter pylori.
AB  - Polyamines, such as putrescine, spermidine and spermine, are essential for the
      regulation of cell proliferation and differentiation in most organisms.
      Spermidine synthase catalyzes the transfer of the aminopropyl group from
      decarboxylated S-adenosylmethionine to putrescine in the biosynthesis of
      spermidine. In this study, spermidine synthase of Helicobacter pylori has been
      overexpressed in Escherichia coli and purified. Two kinds of spermidine synthase
      crystals were obtained. One belongs to the monoclinic P2(1) space group, with
      unit-cell parameters a = 62.78, b = 58.24, c = 74.28 A, beta = 90.9 degrees , and
      the other belongs to the orthorhombic C222(1) space group, with unit-cell
      parameters a = 100.43, b = 128.55, c = 143.60 A.

PMID- 15502330
TI  - Crystallization and preliminary X-ray analysis of sulfite dehydrogenase from
      Starkeya novella.
AB  - Crystals of purified heterodimeric sulfite dehydrogenase from Starkeya novella
      have been grown using vapour diffusion. X-ray diffraction data have been
      collected from crystals of the native protein at lambda = 1.0 A and close to the
      iron absorption edge at lambda = 1.737 A. The crystals belong to space group
      P2(1)2(1)2, with unit-cell parameters a = 97.5, b = 92.5, c = 55.9 A. Native data
      have been recorded to 1.8 A resolution and Fe-edge data to 2.5 A.

PMID- 15502331
TI  - Crystallization and preliminary X-ray analysis of the apo form of Escherichia
      coli tryptophanase.
AB  - Tryptophanase from Escherichia coli is a pyridoxal phosphate-dependent
      homotetrametic enzyme with a subunit weight of 52 kDa. It has been crystallized
      in the apo form by the hanging-drop vapour-diffusion method using polyethylene
      glycol 400 as a precipitant and magnesium chloride as an additive. The crystals
      belong to the orthorhombic space group F222, with unit-cell parameters a = 118.4,
      b = 120.1, c = 171.2 A. A 97.8% complete data set to 1.9 A resolution was
      collected at a rotating-anode source from a single frozen crystal. Packing
      density considerations agree with a monomer in the asymmetric unit with a solvent
      content of 55%. Tryptophanase mutants W330F and Y74F were crystallized under the
      same conditions and the crystals diffracted to a resolution limit of 1.9 A. Data
      sets of wild-type crystals soaked with L-tryptophan or pyridoxal phosphate were
      collected, as well as of Y74F mutant soaked with both.

PMID- 15502332
TI  - Crystallization and preliminary X-ray diffraction studies of a protein disulfide
      oxidoreductase from Aquifex aeolicus.
AB  - A protein disulfide oxidoreductase from the thermophilic bacterium Aquifex
      aeolicus has been overexpressed in Escherichia coli and crystallized at 298 K
      using the hanging-drop vapour-diffusion method. Crystals belong to space group
      R32, with unit-cell parameters a = b = 161.1, c = 153.1 A. A complete data set
      has been collected to 2.4 A using synchrotron radiation. Packing-density
      considerations agree with the presence of 2-4 monomers in the asymmetric unit,
      with a corresponding solvent content of 66-32%.

PMID- 15502333
TI  - Crystallization of a core fragment of the flagellar hook protein FlgE.
AB  - A core fragment of the bacterial flagellar hook protein FlgE was overexpressed,
      purified and crystallized. The crystal diffracted to 1.6 A resolution using
      synchrotron X-radiation. The crystal belongs to the orthorhombic crystal system,
      with space group P2(1)2(1)2 and unit-cell parameters a = 128.4, b = 48.8, c =
      96.7 A. SeMet protein was also overexpressed, purified, crystallized and a set of
      2.3 A MAD data was collected.

PMID- 15502334
TI  - Crystallization and preliminary X-ray analyses of the active and the inactive
      forms of family GH-8 chitosanase with subclass II specificity from Bacillus sp.
      strain K17.
AB  - Chitosanase from Bacillus sp. strain K17 (ChoK) belongs to glycoside hydrolase
      family 8 and exhibits subclass II specificity. The purified protein is
      structurally stable over a wide pH range (3-10), but is active in a much narrower
      pH range (4.5-7.5), with optimal activity around pH 6.0. The protein has been
      successfully crystallized at two different pH values corresponding to the active
      and inactive states. The crystals diffract to 1.5 and 2.0 A resolution,
      respectively.

PMID- 15502335
TI  - Crystallization and preliminary X-ray crystallographic studies of mouse autocrine
      motility factor.
AB  - Mouse autocrine motility factor (mAMF), a tumour-secreted cytokine that
      stimulates cell migration in vitro and metastasis in vivo, has been crystallized
      by the hanging-drop vapour-diffusion method. The crystals belong to the
      monoclinic space group P2(1), with unit-cell parameters a = 69.97, b = 115.88, c
      = 73.27 A, beta = 101.76 degrees . There are two subunits (one dimer) per
      asymmetric unit. Complexes with four-, five- and six-carbon carbohydrate
      phosphate inhibitors have also been crystallized. The crystals diffract to at
      least 1.8 A resolution and are suitable for X-ray structure analyses at high
      resolution.

PMID- 15502336
TI  - Crystallization and preliminary X-ray analysis of a proteinase-K-resistant domain
      within the phosphoprotein of vesicular stomatitis virus (Indiana).
AB  - Several stable domains of the phosphoprotein (P) of vesicular stomatitis virus
      (Indiana) were identified by limited proteolysis of purified recombinant P
      protein expressed in Escherichia coli. The proteinase-K-resistant domain could be
      crystallized using ammonium sulfate as a precipitant and ethylene glycol as an
      additive. The crystals belong to space group P4(1)2(1)2 or P4(3)2(1)2, with unit
      cell parameters a = b = 74.50, c = 156.84 A. X-ray diffraction data were
      collected to 2.75 A resolution at a synchrotron-radiation source.

PMID- 15502337
TI  - Glutamate-5-kinase from Escherichia coli: gene cloning, overexpression,
      purification and crystallization of the recombinant enzyme and preliminary X-ray
      studies.
AB  - Glutamate-5-kinase (G5K) catalyzes the first step of proline (and, in mammals,
      ornithine) biosynthesis. It is a key regulatory point of these routes, since it
      is the subject of feedback allosteric inhibition by proline or ornithine. The
      Escherichia coli gene (proB) for G5K was cloned in pET22, overexpressed in E.
      coli, purified in a few steps in high yield to 95% homogeneity in the highly
      active proline-inhibitable form and was shown by cross-linking to be a tetramer.
      It was crystallized by the hanging-drop vapour-diffusion method at 294 K in the
      presence of ADP, MgCl(2) and L-glutamate using 1.6 M MgSO(4), 0.1 M KCl in 0.1 M
      MES pH 6.5 as the crystallization solution. The tetragonal bipyramid-shaped
      crystals diffracted to 2.5 A resolution using synchrotron radiation. The crystals
      belong to space group P4(1(3))2(1)2, with unit-cell parameters a = b = 101.1, c =
      178.6 A, and contain two monomers in the asymmetric unit, with 58% solvent
      content.

PMID- 15502338
TI  - Crystallization and preliminary X-ray crystallographic studies of human 2',3'
      cyclic nucleotide 3'-phosphodiesterase.
AB  - The catalytic fragment of human 2',3'-cyclic nucleotide 3'-phosphodiesterase
      (hCNP-CF) has been crystallized by the hanging-drop vapour-diffusion method using
      polyethylene glycol 300 as the precipitating agent. The crystals belong to the
      orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 44.39, b =
      55.35, c = 78.76 A. There is one molecule per asymmetric unit. The crystals
      diffract to at least 1.8 A resolution using synchrotron radiation and are
      suitable for X-ray structure analysis at high resolution.

PMID- 15502339
TI  - Crystallographic characterization of the N-terminal domain of PEX1.
AB  - Peroxisomal enzymes are responsible for several primary metabolism pathways,
      including beta-oxidation and lipid biosynthesis. PEX1 and PEX6 are hexameric AAA
      type ATPases and both are necessary for the import of more than 50 peroxisomal
      resident proteins from the cytosol into peroxisomes. In this study, PEX1 N
      terminal domain crystals have been prepared. The crystals belong to space group
      P3(1) or P3(2), with unit-cell parameters a = b = 63.5 A, c = 33.5 A, and contain
      one protein molecule per crystallographic asymmetric unit. An intensity data set
      was collected to a resolution of 2.05 A.

PMID- 15502340
TI  - Purification, identification and preliminary crystallographic characterization of
      a novel seed protein from Vigna unguiculata.
AB  - A tropical legume, Vigna unguiculata, was explored in order to identify potential
      allergens among the abundant seed proteins and to attempt their crystallographic
      study. Salt fractionation of the seed extract followed by chromatographic
      separation led to the purification of a 25 kDa protein. Gel-filtration
      chromatography of the 80% ammonium sulfate precipitation fraction led to
      separation of this protein in pure form, which was subjected to N-terminal
      sequencing. The N-terminal sequences of internal fragments of this protein showed
      85% homology to mung bean seed albumin. This family of proteins is known to be
      intrinsically allergenic. Rhombic shaped crystals were obtained that diffracted
      to about 2.1 A resolution. The crystals belong to space group C2 and have unit
      cell parameters a = 124.9, b = 60.1, c = 67.5 A, beta = 111.1 degrees .

PMID- 15502341
TI  - Purification, crystallization and preliminary X-ray structure analysis of the
      banana lectin from Musa paradisiaca.
AB  - The banana lectin from Musa paradisiaca, MW 29.4 kDa, has been isolated, purified
      and crystallized. The trigonal crystals contain one dimeric molecule in the
      asymmetric unit. The structure has been solved using molecular replacement to a
      resolution of 3 A. The structure of the subunit is similar to that of jacalin
      like lectins.

PMID- 15502342
TI  - Crystallization of a proteolyzed form of the horse pancreatic lipase-related
      protein 2: structural basis for the specific detergent requirement.
AB  - Horse pancreatic lipase-related proteins PLRP1 and PLRP2 are produced by the
      pancreas together with pancreatic lipase (PL). Sequence-comparison analyses
      reveal that the three proteins possess the same two-domain organization: an N
      terminal catalytic domain and a C-terminal domain, which in PL is involved in
      colipase binding. Nevertheless, despite the high level of sequence identity
      found, they exhibit distinct enzymatic properties. The intrinsic sensitivity of
      the peptide bond between Ser245 and Thr246 within the flap region of PLRP2 to
      proteolytic cleavage probably complicates PLRP2 crystallization since, as shown
      here, this proteolyzed form of PLRP2 is only crystallized after specific
      detergent stabilization of this region. This has been performed by the hanging
      drop vapour-diffusion method at 291 K and exclusively in the presence of N,N
      dimethyldecylamine-beta-oxide (DDAO). However, most crystals (>95%) are highly
      twinned and diffract poorly (to approximately 7-5 A resolution). Diffraction
      quality trigonal crystals have unit-cell parameters a = b = 128.4, c = 85.8 A and
      belong to space group P3(2)21. A 2.9 A native data set was collected at ESRF on
      beamline ID14-2 with an R(merge) of 12.7%. Preliminary structural analysis
      provides a structural basis for the specific roles of DDAO.

PMID- 15502343
TI  - Structure of the phenazine biosynthesis enzyme PhzG.
AB  - PhzG is a flavin-dependent oxidase that is believed to play a role in phenazine
      antibiotic synthesis in various bacteria, including Pseudomonas. Phenazines are
      chorismic acid derivatives that provide the producing organisms, including the
      opportunistic pathogen P. aeruginosa, with a competitive growth advantage. Here,
      the crystal structures of PhzG from both P. aeruginosa and P. fluorescens solved
      in an unliganded state at 1.9 and 1.8 A resolution, respectively, are described.
      Although the specific reaction in phenazine biosynthesis catalyzed by PhzG is
      unknown, the structural data indicates that PhzG is closely related to pyridoxine
      5'-phosphate oxidase, the Escherichia coli pdxH gene product, which catalyzes the
      final step in pyridoxal-5'-phosphate (PLP) biosynthesis. A previous proposal
      suggested that the physiological substrate of PhzG to be 2,3-dihydro-3
      hydroxyanthranilic acid (DHHA), a phenazine precursor produced by the sequential
      actions of the PhzE and PhzD enzymes on chorismate, and that two DHHA molecules
      dimerized in another enzyme-catalyzed reaction to yield phenazine-1-carboxylate.
      However, it was not possible to demonstrate any in vitro activity upon incubation
      of PhzG and DHHA. Interestingly, analysis of the in vitro activities of PhzG in
      combination with PhzF suggests that PhzF acts on DHHA and that PhzG then reacts
      with a non-aromatic tricyclic phenazine precusor to catalyze an
      oxidation/aromatization reaction that yields phenazine-1-carboxylate. It is
      proposed that phzG arose by duplication of pdxH and that the subtle differences
      seen between the structures of PhzG and PdxH correlate with the loss of the
      ability of PhzG to catalyze PLP formation. Sequence alignments and
      superimpositions of the active sites of PhzG and PdxH reveal that the residues
      that form a positively charged pocket around the phosphate of PLP in the PdxH-PLP
      complex are not conserved in PhzG, consistent with the inability of
      phosphorylated compounds to serve as substrates for PhzG.

PMID- 15502345
TI  - Protein traffic for secretion and related machinery of Bacillus subtilis.
AB  - Gram-positive sporulating Bacillus subtilis secretes high levels of protein. Its
      complete genome sequence, published in 1997, encodes 4,106 proteins.
      Bioinformatic searches have predicted that about half of all B. subtilis proteins
      are related to the cell membrane through export to the extracellular medium,
      insertion, and attachment. Key features of the B. subtilis protein secretion
      machinery are the absence of an Escherichia coli SecB homolog and the presence of
      an SRP (signal recognition particle) that is structurally rather similar to human
      SRP. In addition, B. subtilis contains five type I signal peptidases (SipS, T, U,
      V, and W). Our in vitro assay system indicated that co-operation between the SRP
      protein targeting system to the cell membrane and the Sec protein translocation
      machinery across the cytoplasmic membrane constitutes the major protein secretion
      pathway in B. subtilis. Furthermore, the function of the SRP-Sec pathway in
      protein localization to the cell membrane and spore was analyzed.

PMID- 15502346
TI  - Effect of MMP/ADAM inhibitors on goblet cell hyperplasia in cultured human
      bronchial epithelial cells.
AB  - While epidermal growth factor receptor (EGFR) plays a pivotal role in the repair
      process of epithelial cells, it is also involved in the overproduction of mucus
      and goblet cell hyperplasia (GCH), which occurs in chronic airway diseases such
      as asthma. Among the EGFR ligands, transforming growth factor (TGF)-alpha is
      thought to be the most important in the synthesis of mucus. Pro-TGF-alpha is
      cleaved to give an active form by members of the matrix metalloproteinases
      (MMP)/a disintegrin and metalloproteinases (ADAM) family. Thus MMP/ADAM
      inhibitors might prevent GCH by inhibiting transactivation of EGFR. Upon
      stimulation of differentiating normal human bronchial epithelial (NHBE) cells by
      IL-13, GCH was induced. The mucin genes MUC5AC, MUC5B, and MUC2 were upregulated
      whereas the expression of ciliated cell markers was greatly repressed. GM6001, a
      broad-spectrum inhibitor for MMP/ADAM, inhibited IL-13-induced mucin gene
      expression and mucus production as measured by periodic acid-Schiff staining.
      This was accompanied by an inhibition of TGF-alpha release. These results suggest
      that MMP/ADAMs play a pivotal role in the development of GCH in lung epithelial
      cells.

PMID- 15502347
TI  - Glucosylation of phenolic compounds by Pharbitis nil hairy roots: I.
      Glucosylation of coumarin and flavone derivatives.
AB  - Hairy roots of medicinal morning glory (Pharbitis nil) showed potent
      glucosylation activity against umbelliferone and aesculetin, so the glucosylation
      activity against several phenolic compounds was tested. Some coumarin derivatives
      and flavone derivatives having phenolic hydroxyl groups were incubated with the
      hairy roots. The coumarin derivatives and flavone derivatives almost disappeared
      from the culture medium in half a day. In the case of the coumarin derivatives, a
      7-hydroxyl group was easily glucosylated. A methyl group at C-8 somewhat
      decreased the glucosylation to a hydroxyl group at C-7 of the coumarin skeleton.
      The 4-hydroxy coumarin derivatives were changed to acetophenone-type glucosides
      by incubation with the hairy roots through decarboxylation. Several flavonol
      derivatives were tested for glucosylation by the hairy roots. 3-Hydroxy flavone,
      3.6-dihydroxyflavone and 3,7-dihydroxyflavone were glucosylated to give 3
      glucosylated derivatives. Of these, 3,6-dihydroxyflavone was highly glucosylated,
      but not 3-hydroxyflavone or 3,7-dihydroxyflavone to the same degree. In the case
      of the flavones, a 3-hydroxy group could be predominantly glucosylated, and
      hydroxyl groups on the A and B ring of the flavones affected glucosylation by the
      hairy roots.

PMID- 15502348
TI  - Cloning and enhanced expression of the cytochrome P450nor gene (nicA; CYP55A5)
      encoding nitric oxide reductase from Aspergillus oryzae.
AB  - We cloned and characterized the gene and cDNA of Aspergillus oryzae cytochrome
      P450nor (Anor). The Anor gene (nicA; CYP55A5) has a different gene structure from
      other P450nor genes in that it has an extra intron. There were not only two kinds
      of mRNA but also two sets of TATA-box and CCAAT-box, and it appears that this
      gene has two expression patterns, like CYP55A1 of Fusarium oxysporum. A reporter
      analysis using the uidA gene indicated that gene expression of CYP55A5 was
      induced under anaerobic conditions, like CYP55A1. When the CYP55A5 gene was
      overexpressed in A. oryzae, a large amount of active Anor were accumulated as
      intracellular protein. Anor employed both NADH and NADPH as electron donors for
      reducing nitric oxide to nitrous oxide. Anor measured the amount of NO generated
      from 3-(2-Hydroxy-1-(1-methylethyl)-2-nitrosohydrazino)-1-propanamine (NOC5) with
      a spectrophotometer. The sensitivity was 10 nmol/ml.

PMID- 15502349
TI  - Hazelnut oil administration reduces aortic cholesterol accumulation and lipid
      peroxides in the plasma, liver, and aorta of rabbits fed a high-cholesterol diet.
AB  - Hazelnut oil (HO) is rich in monounsaturated fatty acids and antioxidants. We
      wanted to investigate the effect of HO on lipid levels and prooxidant-antioxidant
      status in rabbits fed a high-cholesterol (HC) diet. An HC diet caused significant
      increases in lipids and lipid peroxide levels in the plasma, liver, and aorta
      together with histopathological atherosclerotic changes in the aorta. Glutathione
      levels, glutathione peroxidase, and glutathione transferase activities decreased
      significantly, but superoxide dismutase activity and vitamin E and C levels
      remained unchanged in the livers of rabbits following HC diet. HO supplementation
      reduced plasma, liver, and aorta lipid peroxide levels and aorta cholesterol
      levels together with amelioration in atherosclerotic lesions in the aortas of
      rabbits fed an HC diet, without any decreasing effect on cholesterol levels in
      the plasma or liver. HO did not alter the antioxidant system in the liver in the
      HC group. Our findings indicate that HO reduced oxidative stress and cholesterol
      accumulation in the aortas of rabbits fed an HC diet.

PMID- 15502350
TI  - The pro-peptide of Streptomyces mobaraensis transglutaminase functions in cis and
      in trans to mediate efficient secretion of active enzyme from methylotrophic
      yeasts.
AB  - Transglutaminase (TGase) from the actinomycete Streptomyces mobaraensis is a
      useful enzyme in the food industry, and development of an efficient production
      system for it would be desirable. Herein we report secretion of TGase in an
      enzymatically active form by methylotrophic yeasts as expression hosts. Secretory
      production of active TGase required a pro-peptide from TGase. When an artificial
      Kex2-endopeptidase recognition site was placed between the pro-peptide and mature
      TGase, secretion and in vitro maturation of TGase depended on Kex2-dependent
      cleavage. Unexpectedly, coexpression of unlinked pro-peptide with mature TGase
      yielded efficient secretion of the active enzyme. These results indicate that the
      pro-peptide from TGase functions not only in an intramolecular but also in an
      intermolecular manner. Site-directed mutagenesis of putative N-glycosylation
      sites increased the productivity of the active TGase further. A recombinant
      Candida boidinii strain was found to secrete active TGase up to 1.83 U/ml (about
      90 mg/l) after 119 h of cultivation.

PMID- 15502351
TI  - Substrate specificities of several prenyl chain elongating enzymes with respect
      to 4-methyl-4-pentenyl diphosphate.
AB  - In order to develop synthetic methods for biologically active homoallylic terpene
      sulfates, we examined the applicability and substrate specificities of several
      prenyl chain elongating enzymes with respect to 4-methyl-4-pentenyl diphosphate
      (homoIPP). The reaction of dimethylallyl diphosphate with homoIPP by use of
      Bacillus stearothermophilus (all-trans)-farnesyl diphosphate synthase resulted in
      efficient yields of cis-(yield: 45.9%) and trans-4,8-dimethylnona-3,7-dien-1-ol
      (homoGOH, 25.5%), which has a carbon skeleton of 4,8-dimethylnona-3-en-1-sulfate,
      an antiproliferative compound from a marine organism (Aiello, A. et al.,
      Tetrahedron, 53, 11489-11492 (1997)). The homoIPP was found to be also active as
      a homoallylic substrate in place of isopentenyl diphosphate for Sulfolobus
      acidocaldarius geranylgeranyl diphosphate synthase to give diphosphate of cis-
      and trans-4,8,12-trimethyltrideca-3,7,11-trien-1-ol, for Micrococcus luteus B-P
      26 hexaprenyl diphosphate synthase to give cis- and trans-4,8,12,16
      tetramethylheptadeca-3,7,11,15-tetraen-1-ol (homoGGOH), and for Micrococcus
      luteus B-P 26 undecaprenyl diphosphate synthase to give cis-homoGGOH exclusively.

PMID- 15502352
TI  - A practical method for measuring deoxynivalenol, nivalenol, and T-2 + HT-2 toxin
      in foods by an enzyme-linked immunosorbent assay using monoclonal antibodies.
AB  - We have developed and tested an enzyme-linked immunosorbent assay system for
      individual measurement of deoxynivalenol, nivalenol, and T-2 + HT-2 toxin using
      monoclonal antibodies for 3,4,15-triacetyl-nivalenol, for both 3,4,15-triacetyl
      nivalenol and 3,15-diacetyl-deoxynivalenol, and for acetyl-T-2 toxin. The assay
      system comprised three kits (desinated the DON + NIV kit, the NIV kit, and the T
      2 + HT-2 kit). The practical performance of the enzyme-linked immunosorbent assay
      system was assessed by assaying trichothecene mycotoxins in wheat kernels. The
      enzyme-linked immunosorbent assay system meets all the requirements for use in a
      routine assay in terms of sensitivity (detection limit: deoxynivalenol 80 ng/g,
      nivalenol 80 ng/g, T-2 toxin 30 ng/g), reproducibility (total coefficient of
      variation: 1.9-6.2%), accuracy (recovery: 93.8-112.0%), simplicity and rapidity
      (time required: <2 h), mass handling (>42 samples/assay), and a good correlation
      with gas chromatography-mass spectrometry (r=0.9146-0.9991). Components derived
      from the wheat extract did not interfere with the assay kits. The enzyme-linked
      immunosorbent assay system is a useful alternative method to gas chromatography
      mass spectrometry, liquid chromatography-mass spectrometry, or liquid
      chromatography-ultraviolet absorption for screening cereals and foods for
      trichothecene mycotoxin contamination.

PMID- 15502353
TI  - Regioselectivity in beta-galactosidase-catalyzed transglycosylation for the
      enzymatic assembly of D-galactosyl-D-mannose.
AB  - The regioselectivity of beta-galactosidase derived from Bacillus circulans ATCC
      31382 (beta-1,3-galactosidase) in transgalactosylation reactions using D-mannose
      as an acceptor was investigated. This D-mannose associated regioselectivity was
      found to be different from reactions using either GlcNAc or GalNAc as acceptors,
      not only for beta-1,3-galactosidase but also for beta-galactosidases of different
      origins. The relative hydrolysis rate of Gal beta-pNP and D-galactosyl-D
      mannoses, of various linkages, was also measured in the presence of beta-1,3
      galactosidase and was found to correlate well with the ratio of disaccharides
      formed by transglycosylation. The unexpected regioselectivity using D-mannose can
      therefore be explained by an anomalous specificity in the hydrolysis reaction. By
      utilizing the identified characteristics of both regioselectivity and hydrolysis
      specificity using D-mannose, an efficient method for enzymatic synthesis of beta
      1,3-, beta-1,4- and beta-1,6-linked D-galactosyl-D-mannose was subsequently
      established.

PMID- 15502354
TI  - Effect of beta-casein (1-28) on proliferative responses and secretory functions
      of human immunocompetent cell lines.
AB  - The effect of bovine beta-casein (1-28) purified from commercial casein
      phosphopeptide preparations on human T, B, and monocyte cell lines was evaluated.
      Beta-casein (1-28) enhanced the proliferation of the following: T cell lines HUT
      78, Jurkat Clone E6-1, and MOLT-4; B cell lines BALL, KHM-1B, and U266B1; and
      monocyte cell lines U937 and HL-60. Moreover, beta-casein (1-28) stimulated IgA
      production by KHM-1B over 96 h of culture. Semiquantitative reverse
      transcriptional-polymerase chain reaction analysis indicated that beta-casein (1
      28) enhanced mRNA expression of interleukin (IL)-6 in U266B1 and KHM-1B. These
      results suggest that beta-casein (1-28) exerts a mitogenic effect on human T, B,
      and monocyte cells, and an IgA-enhancing effect on B cells.

PMID- 15502355
TI  - GroEL chaperone binding to beetle luciferases and the implications for refolding
      when co-expressed.
AB  - The folding of many proteins including luciferase in vivo requires the assistance
      of molecular chaperone proteins. To understand how a chaperone targets
      luciferase, we took three luciferases that give different bioluminescence with
      the same luciferin substrate and with differences in homology. The three
      luciferase genes, firefly luciferase (FF-Luc) (from Pyrocoelia miyako), and red
      (RE-Luc) and green (GR-Luc) bioluminescence-emitting luciferases (from
      Phrixothrix railroad-worms), were expressed in Escherichia coli to produce fusion
      proteins with predicted molecular masses. Subsequently, we observed that DnaK and
      GroEL were co-purified along with recombinant luciferase. Although the amount of
      co-purified DnaK was almost the same compared to FF-Luc, GroEL was 25 and 32
      times higher in GR-Luc and RE-Luc respectively. Furthermore, co-expression of
      GroEL/GroES along with luciferase substantially refolded RE-Luc and GR-Luc
      compared to FF-Luc.

PMID- 15502356
TI  - Effects of cross-sectional area on human bite studied with raw carrot and surimi
      gel.
AB  - The effects of the cross-sectional area of food samples on bite force with molar
      teeth were investigated using raw carrots and surimi gels. We evaluated human
      bite force for food samples with different sizes between the upper and lower
      molars using a multiple-point sheet sensor and electromyography (EMG). The bite
      force curve and EMG clearly showed textural characteristics of the carrot and
      gel. In particular, the first peak in the bite curves corresponded to breaking
      point in the compression test. With increasing cross-sectional area of both
      foodstuffs, the bite force and contact area increased and the average stress to
      which the specimen was subjected (mean stress) tended to decrease, while the
      stress produced between the teeth and the specimen (active stress) did not
      change. Chewing rhythm and EMG activities were not greatly influenced by sample
      size. These findings suggest that higher bite force might cause difficulty in
      biting food with a larger cross-sectional area.

PMID- 15502357
TI  - Cloning and expression of a novel Trichoderma viride laminarinase AI gene
      (lamAI).
AB  - The gene lamAI, which encodes a novel laminarinase AI of Trichoderma viride U-1,
      was cloned using RT-PCR in conjunction with the rapid amplification of cDNA ends
      (RACE) technique. The open reading frame consisted of 2,277 bp encoding a protein
      of 759 amino acid residues, including a 32-residue signal prepropeptide. The
      protein showed 91% sequence similarity to the putative Trichoderma virens beta
      1,3-glucanase BGN1, but no significant similarity to fungal beta-1,6-glucanases
      or beta-1,3-glucanases from other organisms. On 40 h incubation with a solo
      carbon source, northern analysis revealed that the gene was induced by 0.5%
      laminaran from Eisenia bicyclis but was not by the same concentration of glucose.
      The lamAI cDNA was functionally expressed in the methylotrophic yeast Pichia
      pastoris, resulting in a recombinant enzyme with as high activity against
      laminaran as native LAMAI. Based on these data, the probable existence of endo
      beta-1,3:1,6-glucan hydrolases as a subclass of endo-beta-1,3-glucanases in some
      mycoparasitic fungi is suggested.

PMID- 15502358
TI  - A novel zinc-containing alpha-keto ester reductase from actinomycete: an approach
      based on protein chemistry and bioinformatics.
AB  - We have achieved the purification of an alpha-keto ester reductase (SCKER) from
      S. coelicolor A3(2) whole cells. SCKER proved to be a homotetramer of 132 kDa
      containing one equivalent of zinc ion per subunit. The enzyme differed from other
      alpha-keto ester reductases from microorganisms with regard to subunit structure
      and metal ion dependency. From a computer search using the protein data banks,
      the N-terminal amino acid sequence of SCKER was consistent with that of a
      possible zinc containing alcohol dehydrogenase in S. coelicolor A3(2). None of
      three hypothetical proteins of S. coelocor A3(2) having a high homology sequence
      with those of already purified alpha-keto ester reductases from S.
      thermocyaneoviolaceus [Yamaguchi, H., et al., Biosci. Biotechnol. Biochem., 66,
      588-597 (2002)] was identical with that of SCKER.

PMID- 15502359
TI  - Cleavage of various peptides with pitrilysin from Escherichia coli: kinetic
      analyses using beta-endorphin and its derivatives.
AB  - Pitrilysin from Escherichia coli was overproduced, purified, and analyzed for
      enzymatic activity using 14 peptides as a substrate. Pitrilysin cleaved all the
      peptides, except for two of the smallest, at a limited number of sites, but
      showed little amino acid specificity. It cleaved beta-endorphin (beta-EP) most
      effectively, with a K(m) value of 0.36 microM and a k(cat) value of 750 min(-1).
      beta-EP consists of 31 residues and was predominantly cleaved by the enzyme at
      Lys(19)-Asn(20). Kinetic analyses using a series of beta-EP derivatives with N
      and/or C-terminal truncations and with amino acid substitutions revealed that
      three hydrophobic residues (Leu(14), Val(15), and Leu(17)) and the region 22-26
      in beta-EP are responsible for high-affinity recognition by the enzyme. These two
      regions are located on the N- and C-terminal sides of the cleavage site in beta
      EP, suggesting that the substrate binding pocket of pitrilysin spans its
      catalytic site.

PMID- 15502360
TI  - Gene cloning and biochemical characterizations of thermostable ribonuclease HIII
      from Bacillus stearothermophilus.
AB  - The gene encoding RNase HIII from the thermophilic bacterium Bacillus
      stearothermophilus was cloned and overexpressed in Escherichia coli, and the
      recombinant protein (Bst-RNase HIII) was purified and biochemically
      characterized. Bst-RNase HIII is a monomeric protein with 310 amino acid
      residues, and shows an amino acid sequence identity of 47.1% with B. subtilis
      RNase HIII (Bsu-RNase HIII). The enzymatic properties of Bst-RNase HIII, such as
      pH optimum, metal ion requirement, and cleavage mode of the substrates, were
      similar to those of Bsu-RNase HIII. However, Bst-RNase HIII was more stable than
      Bsu-RNase HIII, and the temperature (T(1/2)) at which the enzyme loses half of
      its activity upon incubation for 10 min was 55 degrees C for Bst-RNase HIII and
      35 degrees C for Bsu-RNase HIII. The optimum temperature for Bst-RNase HIII
      activity was also shifted upward by roughly 20 degrees C as compared to that of
      Bsu-RNase HIII. The availability of such a thermostable enzyme will facilitate
      structural studies of RNase HIII.

PMID- 15502361
TI  - Utility of dry gel from two-dimensional electrophoresis for peptide mass
      fingerprinting analysis of silkworm proteins.
AB  - We compared the use of wet and dry two-dimensional electrophoresis (2-DE) gels
      for in-gel tryptic digestion and subsequent analysis by mass spectrometry, first
      using bovine serum albumin (BSA) as a model protein and then using unknown
      proteins from an extract of the silkworm midgut. The gel was either dried at 80
      degrees C or left wet. Upon analysis of BSA, there was little difference in
      peptide recovery from 2-DE or in mass spectrum between the dry and the wet gels.
      The midgut extract was resolved into more than 1,100 protein spots by 2-DE, and
      40 of these spots were sampled for further analysis. For all of the 40 proteins,
      the results obtained from dry and wet gels were quite similar in mass spectra and
      protein identification, although the relative amounts of peptides from tryptic
      digestion ranged from 45 to 146%. Based on these results, we confirmed the
      utility of dry electrophoretic gels for proteomics of insect extracts.

PMID- 15502362
TI  - Dietary resistant starch alters the characteristics of colonic mucosa and exerts
      a protective effect on trinitrobenzene sulfonic acid-induced colitis in rats.
AB  - The protective effect of a dietary high-amylose cornstarch (HAS) against
      trinitrobenzene sulfonic acid (TNBS)-induced colitis was examined in rats. Rats
      were fed a HAS-free basal diet or, a 15% or 30% HAS supplemented diet for 10 d,
      and then received intracolonic TNBS to induce colitis and fed the respective
      diets for a further 8 d. HAS ingestion significantly protected colonic injuries
      as evidenced by lower colonic myeloperoxidase activity. Rats fed the HAS diet
      showed greater cecal short-chain fatty acid (SCFA) production than those fed the
      basal diet. Further, just before TNBS administration, HAS ingestion dose
      dependently increased fecal and cecal mucin contents, and protein and nucleic
      acid contents in the colonic mucosa. HAS ingestion also reduced colonic
      permeability. The protective effect of HAS ingestion on TNBS-induced colitis is
      perhaps exerted through alterations in colonic mucosa, possibly due to cecal SCFA
      production.

PMID- 15502363
TI  - Spectrophotometric and kinetic studies on the binding of the bioflavonoid
      quercetin to bovine serum albumin.
AB  - This work investigates the binding of the bioflavonoid, quercetin, to bovine
      serum albumin (BSA) by spectrophotometric techniques involving both the
      conventional and stopped-flow methods. Both the neutral and negatively-charged
      forms of quercetin bound to BSA with a red shift in the maximal absorption. At
      high pH values, quercetin was rapidly degraded in an oxygen-dependent process,
      but this decomposition was substantially slower when the flavonoid was bound to
      BSA. At pH 7.4, the difference spectrum of quercetin with and without BSA was
      maximal at 425 nm; this wavelength can be conveniently used to monitor the extent
      and speed of binding. Spectrophotometric studies with a range of equimolar
      mixtures of quercetin and BSA at pH 7.4 suggest the binding was maximal when the
      concentration was 10 microM. It is postulated that the binding site of BSA for
      quercetin was less available at higher protein concentrations, perhaps because of
      conformational change or self-association. The rate of spectrophotometric change
      when quercetin bound to BSA was fairly slow; the process was not quite complete
      within 45 seconds and was biphasic. When a pre-mixed equimolar mixture of BSA and
      quercetin was diluted with an equal volume of the buffer, there was a surprising
      further increase in absorbance at 425 nm (rather than the fall anticipated if the
      binary complex were to dissociate). It is concluded that, upon dilution, the
      effective concentration of BSA's binding site increased, providing more scope for
      quercetin to bind.

PMID- 15502364
TI  - Biotransformation of various alkanes using the Escherichia coli expressing an
      alkane hydroxylase system from Gordonia sp. TF6.
AB  - Biotransformation using alkane-oxidizing bacteria or their alkane hydroxylase
      (AH) systems have been little studied at the molecular level. We have cloned and
      sequenced genes from Gordonia sp. TF6 encoding an AH system, alkB2 (alkane 1
      monooxygenase), rubA3 (rubredoxin), rubA4 (rubredoxin), and rubB (rubredoxin
      reductase). When expressed in Escherichia coli, these genes allowed the
      construction of biotransformation systems for various alkanes. Normal alkanes
      with 5 to 13 carbons were good substrates for this biotransformation, and
      oxidized to their corresponding 1-alkanols. Surprisingly, cycloalkanes with 5 to
      8 carbons were oxidized to their corresponding cycloalkanols as well. This is the
      first study to achieve biotransformation of alkanes using the E. coli expressing
      the minimum component genes of the AH system. Our biotransformation system has
      facilitated assays and analysis leading to improvement of AH systems, and has
      indicated a cycloalkane oxidation pathway in microorganisms for the first time.

PMID- 15502365
TI  - Structure-activity relationship for FR901464: a versatile method for the
      conversion and preparation of biologically active biotinylated probes.
AB  - The structure-activity relationship for FR901464, a potent cell-cycle inhibitor,
      was examined by synthesizing its analogs. A versatile method for converting
      FR901464 was devised. This method made it possible to synthesize biologically
      active FR901464-biotin conjugates which could be used to isolate the binding
      proteins.

PMID- 15502366
TI  - Synthesis and antioxidative activity of 3',4',6,7-tetrahydroxyaurone, a
      metabolite of Bidens frondosa.
AB  - 3',4',6,7-Tetrahydroxyaurone (1a), an aurone isolated from Bidens frondosa, and
      five analogues (1b-1f) were synthesized from pyrogallol in three steps. The
      antioxidative activity of 1a-1f was determined by the superoxide free radical and
      1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging methods.

PMID- 15502367
TI  - Effect of moisture content on the expansion volume of popped Amaranth seeds by
      hot air and superheated steam using a fluidized bed system.
AB  - The effect of the initial moisture content (X(0)) of amaranth seeds on expansion
      volume after popping was examined in hot air and superheated steam (SHS), using a
      fluidized bed system (FBS). The moisturized seeds were prepared under various
      vapor pressures due to various saturated salt solutions. In hot air, the maximum
      expansion volume was shown by seeds having X(0) of 0.16 at 260 degrees C for 15
      sec, reaching 8.7-fold of the pre-popped seeds. Heating by SHS decreased the
      volume slightly. Thus, popping of amaranth seeds is influenced not only by the
      moisture content of the seeds, but also by moisture in the heat media.

PMID- 15502368
TI  - Detection of antigen-antibody reaction using a fluorescent probe and its
      application to homogeneous competitive-type immunoassay for insulin.
AB  - The interaction of bovine insulin with anti-human insulin antibody (mAb) was
      examined using a fluorescent probe. The fluorescence intensity of
      fluoresceinthiocarbamyl (FTC)-insulin was increased by adding mAb, and the
      increase was saturated at 53% at a molar ratio of FTC-insulin to mAb of 2.0.
      Based on the change in fluorescence intensity, a standard curve of the
      homogeneous competitive-type immunoassay was constructed, and the detection range
      of insulin was found to be 50-400 nM.

PMID- 15502369
TI  - Purification and antifungal activity of recombinant chitinase from Escherichia
      coli carrying the family 19 chitinase gene of Streptomyces sp. J-13-3.
AB  - A recombinant chitinase was purified from the cell extract of Escherichia coli
      JM109 transformed by plasmid pUC19 carrying the gene encoding family 19 chitinase
      of Streptomyces sp. J-13-3 by column chromatography on DEAE-Sepharose, CM
      Sepharose, and Bio-Gel P-100. The final preparation was homogenous in
      polyacrylamide gel electrophoresis. The molecular weight of the purified enzyme
      was estimated to be 32,000. The recombinant chitinase hydrolyzed the trimer to
      hexamer of N-acetylglucosamine and had the identical N-terminal amino acid
      sequence of the mature protein, indicating removal of the signal sequence by E.
      coli signal peptidase. The fungal growth in well (200 microl of medium) of
      microplate by measurement of absorbance at 595 nm indicated that the chitinase
      (10 microg) completely and half inhibited growth of Trichoderma reesei and
      Aspergillus niger respectively.

PMID- 15502370
TI  - A synthetic polymer, poly(2-methacryloyloxyethyl phosphorylcholine-co-n-stearyl
      methacrylate), stimulates insulin release from RINm5F insulinoma cells.
AB  - A water-soluble phospholipid-like polymer, poly(2-methacryloyloxyethyl
      phosphorylcholine-co-n-stearyl methacrylate) (PMC(18), average molecular weight =
      4.3 x 10(4)), at a concentration (0.5-5 mg/ml) showing no inhibition of cell
      proliferation, stimulated insulin release from RINm5F rat insulinoma cells in a
      concentration- and time-related manner. But poly(2-methacryloyloxyethyl
      phosphorylcholine) and other synthetic phospholipid-like polymers failed to
      stimulate insulin release.

PMID- 15502371
TI  - Absolute stereochemistry of acremolactone A, a novel herbicidal
      epoxydihydropyranyl gamma-lactone from Acremonium roseum I4267.
AB  - Acremolactone A was chemically degraded to the bicyclic hemiacetal gamma-lactone
      and an epoxycyclohexenol, and their stereochemistry was determined by
      spectroscopic methods. These observations and data from NOE experiments on
      acremolactone A led to the configurational assignment of all asymmetric carbons
      in acremolactone A, enabling its stereostructure to be established.

PMID- 15502372
TI  - Content and chemical compositions of cerebrosides in lactose-assimilating yeasts.
AB  - Cerebrosides were found in ten lactose-assimilating yeasts. Representative
      component ceramide moieties of cerebrosides from nine of these yeasts contained 9
      methyl-4-trans, 8-trans-sphingadienine, and 2-hydroxy fatty acid with carbon
      chain lengths of 16 or 18. The major ceramide moieties in Brettanomyces anomalus,
      however, differed from those in other yeasts, and were predominately moieties
      containing 2-hydroxymyristic acid. Thus we found that various cerebroside
      molecular species are present in yeasts.

PMID- 15502373
TI  - Transcriptional coactivator p300/CBP-associated factor and p300/CBP-associated
      factor type B are required for normal estrogen response of the mouse uterus.
AB  - Mice with targeted gene disruption of one of the estrogen receptor coactivators,
      p300/CBP-associated factor (PCAF), and its counterpart, PCAF-B, were used to
      investigate the possible involvement of PCAF and PCAF-B in estrogen receptor
      mediated actions in vivo. Among ovariectomized mice that were treated with
      estrogen, PCAF and PCAF/PCAF-B knockouts showed abnormal growth of the uterus
      compared with the wild type. The level of c-fos gene expression in the uterus was
      not induced by estrogen in the knockouts. These observations suggest that PCAF
      and PCAF-B are required for estrogen-dependent normal growth of the uterus via
      estrogen receptor-mediated transcriptional regulations.

PMID- 15502374
TI  - Biosynthesis of fukinolic acid isolated from Petasites japonicus.
AB  - The biosynthesis of fukinolic acid, which had been isolated from the Japanese
      fuki vegetable, Petasites japonicus, was investigated by feeding selected (13)C
      labeled compounds to axenic cultures of P. japonicus. [1,2-(13)C(2)] sodium
      acetate and [1-(13)C] L-tyrosine were incorporated into the fukiic acid sub
      group, while [3-(13)C] L-phenylalanine was incorporated into the caffeic acid
      moiety.

PMID- 15502375
TI  - Adiponectin as a biomarker of the metabolic syndrome.
AB  - BACKGROUND: The metabolic syndrome, a cluster of abdominal obesity, dyslipidemia,
      hypertension and hyperglycemia, is a common basis for atherosclerotic vascular
      diseases in industrial countries exposed to overnutrition. Adiponectin is an
      adipose-derived plasma protein with anti-atherogenic and insulin-sensitizing
      activities. METHODS AND RESULTS: A total of 661 Japanese adults (479 men, 53+/-10
      years; 182 women 56+/-10 years) were enrolled. Plasma adiponectin concentrations
      correlated negatively with waist circumference, visceral fat area, serum
      triglyceride concentration, fasting plasma glucose, fasting plasma insulin, and
      systolic and diastolic blood pressure in both sexes. A positive correlation was
      found between plasma adiponectin and high-density lipoprotein cholesterol
      concentrations in both sexes. The mean number of components of the metabolic
      syndrome increased as the plasma adiponectin concentration decreased: 2.57+/-1.34
      for men and 2.00+/-1.51 for women with adiponectin concentrations <4.0 microg/ml.
      In all, 52.3% of men and 37.5% of women with adiponectin concentrations <4.0
      microg/ml fulfilled the criteria for metabolic syndrome. CONCLUSION:
      Hypoadiponectinemia is closely associated with the clinical phenotype of the
      metabolic syndrome and measuring the plasma concentration of adiponectin may be
      useful for management of the metabolic syndrome.

PMID- 15502376
TI  - Relationship between abdominal visceral fat and lacunar infarcts in Japanese men.
AB  - BACKGROUND: The relationship between abdominal visceral fat accumulation and
      lacunar infarcts has not been previously investigated in Japanese men. METHODS
      AND RESULTS: The subjects were 637 middle-aged (40-64 years) and 222 elderly (65
      79 years) men who participated in a health checkup program from 1999 to 2003. The
      association between lacunar infarcts identified by magnetic resonance imaging and
      cardiovascular risk factors, including abdominal visceral fat accumulation
      evaluated by computed tomography, was examined. The prevalence of lacunar
      infarcts was 4.9%. Hypertension was associated with lacunar infarcts among both
      the middle-aged men [age-adjusted odds ratio (OR)=2.9 (95% confidence interval
      (CI): 1.1-7.8)] and the elderly men [OR=5.1 (95%CI: 1.4-19.0)]. Abdominal
      visceral fat accumulation was slightly associated with lacunar infarcts among
      middle-aged men, but not among elderly men: OR in the highest (>or=117 cm(2)) vs
      lowest (<or=83 cm(2)) tertiles of fat area was 2.6 (95%CI: 0.9-7.6) for middle
      aged men. Extreme accumulation of visceral fat (>or=143 cm(2)) was still slightly
      associated with lacunar infarcts after adjustment for age, hypertension, drinking
      and smoking among middle-aged men [OR=2.7 (95%CI: 0.8-9.1)]. CONCLUSIONS: This
      cross-sectional study suggests that abdominal visceral fat accumulation is a
      possible risk factor of lacunar infarcts, in addition to hypertension, in middle
      aged Japanese men.

PMID- 15502377
TI  - Differences in the clinical course of acute massive and submassive pulmonary
      embolism.
AB  - BACKGROUND: Acute massive or submassive pulmonary embolism (PE) has high
      mortality, but the clinical course according to the location of onset (ie, in
      hospital or out-of-hospital) is unknown. METHODS AND RESULTS: In the present
      study 56 consecutive patients with acute massive or submassive PE were studied
      retrospectively and a comparison made of the clinical characteristics, and
      outcomes between in-hospital onset (Group A) and out-of-hospital onset (Group B).
      Patients in Group A (n=28) had more frequent comorbidities with hemodynamic
      instability (54% vs 4%, p<0.0001) and temporary risk factors (93% vs 11%,
      p<0.0001), whereas patients in Group B (n=28) had a longer duration of symptoms
      (median: 5.5 days vs 0.5 day; p<0.0001), and had higher systolic pulmonary artery
      pressure (63+/-17 mmHg vs 46+/-12 mmHg, p=0.0006). Although in-hospital mortality
      did not differ between the 2 groups, the recurrence rate was higher in Group B
      (23% vs 0%, p=0.03). CONCLUSIONS: Patients who had in-hospital onset of PE had
      mostly temporary risk factors, unstable hemodynamics and a lower recurrence rate
      compared with the cases of out-of-hospital onset. In cases of in-hospital onset,
      prompt diagnosis and suitable treatment is needed to prevent fatalities and cases
      of out-of-hospital onset should be followed carefully for recurrence.

PMID- 15502378
TI  - Application of pressure-derived myocardial fractional flow reserve in assessing
      the functional severity of coronary artery stenosis in patients with diabetes
      mellitus.
AB  - BACKGROUND: Although the development of a coronary guidewire mounted with a
      pressure sensor has facilitated the measurement of pressure-derived fractional
      flow reserve (FFR) to assess the functional severity of coronary artery stenoses,
      the theoretical limitations include diabetes mellitus because of the associated
      microvascular abnormalities. METHODS AND RESULTS: In the present study 304
      vessels and their coronary territories in 96 diabetic and 149 nondiabetic
      patients were evaluated by pressure-derived FFR and thallium-201 single photon
      emission computed tomography (SPECT) to determine the applicability of measuring
      FFR in diabetic subjects. The best cut-off value for FFR to detect myocardial
      ischemia, as demonstrated by (201)Tl SPECT, was 0.725 in the diabetic and 0.745
      in the nondiabetic patients. Sensitivity and specificity were similar for the 2
      groups (83% and 75% (diabetic) vs 79% and 83%). However, diabetic patients with
      homoglobin (Hb) A(1c) >or=7.0% showed lower specificity in comparison with those
      having HbA(1c) <7.0% (64 vs 88%; p=0.045); however, sensitivities were similar
      (83 vs 83%; p=NS). CONCLUSIONS: The cut-off value of 0.75 for FFR can detect
      myocardial ischemia in diabetic patients, although the adequacy of glycemic
      control should be taken into consideration when assessing the FFR measurements.

PMID- 15502379
TI  - Factors predicting success in cryoablation of the pulmonary veins in patients
      with chronic atrial fibrillation.
AB  - BACKGROUND: This study was designed to investigate the factors predicting
      maintenance of sinus rhythm (SR) in patients with chronic atrial fibrillation
      (AF) undergoing cryoablation of the pulmonary veins (PV-cryo) during cardiac
      surgery. METHODS AND RESULTS: Seventy-seven patients with AF undergoing PV-cryo
      were recruited and divided into 2 groups based on whether they were able to
      maintain SR at discharge. The duration of AF (AF-D), left atrial dimension (LAd),
      and the average of the peak left atrial appendage outflow velocities (LAA-V)
      before surgery were determined for both groups. Group SR consisted of 54 patients
      (70%), and group AF consisted of 23 patients (30%). All patients with an AF-D
      <or=3 years, LAd <45 mm and LAA-V >40 cm/s were in group SR and all those with an
      AF-D >10 years and LAd >or=65 mm were in group AF. Only 71% of patients with a
      LAA-V <or=20 cm/s were in group AF. CONCLUSIONS: Restoration of AF to SR by PV
      cryo can be predicted from a knowledge of the AF-D, LAd and LAA-V.

PMID- 15502380
TI  - Echocardiographic predictors of remote outcome in patients with angiographically
      successful reflow after acute myocardial infarction.
AB  - BACKGROUND: The angiographically no-reflow phenomenon after percutaneous coronary
      intervention (PCI) predicts poor left ventricular (LV) functional recovery and a
      high risk of cardiac events in patients with their first acute myocardial
      infarction (AMI). However, risk factors of long-term adverse outcome for patients
      with angiographically successful reflow (TIMI (Thrombolysis in Myocardial
      Infarction) flow grade 3) for the AMI remain unknown. METHODS AND RESULTS: Of 168
      echocardiograms were performed before PCI and at discharge, 113 were suitable for
      analysis. Clinical, angiographic, and echocardiographic variables were submitted
      to statistical analysis to detect the risk factors of cardiac events. During the
      follow-up period of 46+/-20 months, 31 patients had cardiac events, though there
      were no cardiac deaths. The 2 most important risk factors for congestive heart
      failure (CHF) or total cardiac events were LV dilation (chi-square: 7.5 and 9.4;
      both p<0.01) and pseudonormal transmitral flow pattern (PN, chi-square: 4.9,
      p<0.05 and 6.7, p<0.01, respectively). However, only multivessel disease (chi
      square: 9.4, p=0.05) became the predictor for revascularization after PCI. The
      incidence of CHF or total cardiac events in patients with PN and LV dilation at
      discharge determined by the Kaplan-Meier method were significantly higher than
      those with normal or abnormal relaxation transmitral flow pattern (log-rank: 41
      and 27, both p<0.001) and no LV dilation (log-rank: 20 and 20, both p<0.001).
      CONCLUSION: Poor LV diastolic function and LV dilation at discharge are
      predictors of the cardiac events in patients in whom epicardial coronary flow was
      well-restored after PCI for the first AMI.

PMID- 15502381
TI  - Environmental factors and risk of idiopathic dilated cardiomyopathy: a multi
      hospital case-control study in Japan.
AB  - BACKGROUND: Detailed epidemiological investigations on the relationship of
      environmental factors, especially occupational and microbiological factors, to
      the development of idiopathic dilated cardiomyopathy (IDC) are scarce. METHODS
      AND RESULTS: A multi-hospital case-control study was conducted in 38 hospitals
      throughout Japan in order to survey IDC cases and age, sex-matched outpatient
      controls at each hospital. Crude and adjusted odds ratios (ORs) by various
      environmental factors were calculated in 135 pairs of cases and controls.
      Univariate analyses revealed significantly increased ORs for lower education,
      passive smoking in the workplace, cold and/or hot workplace, symptoms of fatigue
      and history of bacterial infection; in contrast, decreased ORs were associated
      with a history of rubella and gastroduodenal diseases. Based on multivariate
      adjusted analyses, lower education (OR 1.96, 95% confidence interval (CI) 1.13
      3.40), cold or hot workplace (OR 1.84, 95%CI 1.08-3.12) and history of measles
      (OR 1.78, 95%CI 1.01-3.08) exhibited a significant positive relationship with IDC
      risk. History of rubella (OR 0.17, 95%CI 0.06-0.52) and gastroduodenal diseases
      (OR 0.14, 95%CI 0.07-0.29) were inversely related to the risk. CONCLUSIONS: Some
      occupational and microbiological factors appear to relate independently to the
      development of IDC and further investigation is required to establish their
      respective mechanisms.

PMID- 15502382
TI  - Clinical significance of electrocardiography recordings from a higher intercostal
      space for detection of the brugada sign.
AB  - BACKGROUND: The significance of higher intercostal space electrocardiography
      (HICS ECG) for the detection of the Brugada sign was investigated. METHODS AND
      RESULTS: The subjects consisted of 113 cases (108 males, 5 females; mean age,
      57+/-17 years) with incomplete right bundle branch block type QRS morphology and
      ST-segment elevation (>0.10 mV) in the right precordial leads. Obvious structural
      heart disease was not observed in any of the subjects. The V(1-3) leads of the
      standard 12-lead ECG and the HICS ECG were recorded in the supine position, and
      the amplitude of the terminal portion of the QRS (J-point) and ST-segment (80 ms
      from the J-point) were measured. In the HICS ECG, there was an increase in the
      area in which the Brugada sign was detectable (47 leads to 66 leads), and in
      cases with the Brugada sign, the amplitude of the J-point increased. CONCLUSIONS:
      The HICS ECG may be helpful for the detection of the Brugada sign.

PMID- 15502383
TI  - Diagnostic use of T2-weighted inversion-recovery magnetic resonance imaging in
      acute coronary syndromes compared with 99mTc-Pyrophosphate, 123I-BMIPP and
      201TlCl single photon emission computed tomography.
AB  - BACKGROUND: The incidence of missed diagnoses of acute cardiac ischemia in the
      emergency department could be reduced by a new imaging modality. In the present
      study, the clinical significance of (99m)Tc-pyrophosphate (PYP), (123)I-beta
      methyl-p-iodephenyl-pentadecanoic acid (BMIPP), (201)TlCl scintigraphy (imaging)
      and T2-weighted inversion-recovery magnetic resonance imaging (MRI) for the
      detection of culprit lesion in patients with acute coronary syndromes (ACS) was
      compared. METHODS AND RESULTS: The study group comprised 18 patients with ACS: 12
      patients with acute myocardial infarction (AMI) (11 males; mean age, 63+/-11
      years) and 6 patients with unstable angina (UA) (3 males, mean age, 67+/-5
      years). Of the 12 patients with AMI, 10 underwent (201)TlCl and PYP single photon
      emission computed tomography (SPECT) studies as a dual-energy acquisition
      ((201)TlCl/PYP) and 8 underwent (201)TlCl SPECT within 1 week of the BMIPP study.
      All 18 patients underwent BMIPP SPECT and MRI. The MRI pulse sequence was black
      blood turbo short-inversion-time inversion recovery (STIR) (breath-hold T2
      weighted studies). The T2-weighted inversion-recovery MRI showed higher
      sensitivity and negative predictive value than PYP and (201)TlCl, and higher
      specificity and positive predictive value than BMIPP and (201)TlCl. The area
      under the receiver-operating characteristic curve for PYP, BMIPP, (201)TlCl and
      MRI was 0.787, 0.725, 0.731 and 0.878, respectively. The difference between the
      areas of MRI and BMIPP was significant (p<0.05). CONCLUSION: Accurate detection
      of culprit lesion is improved by using MRI rather than BMIPP, particularly for
      patients with ACS.

PMID- 15502384
TI  - Effects of enhanced external counterpulsation on hemodynamics and its mechanism.
AB  - BACKGROUND: The hemodynamic effects of enhanced external counterpulsation (EECP)
      and its mechanism(s) were investigated in relation to neurohumoral factors in
      patients with acute myocardial infarction (AMI). METHODS AND RESULTS: Twenty-four
      patients with AMI were studied before, during and after EECP treatment for 60
      min. Heart rate (HR), right atrial pressure (RAP), pulmonary capillary wedge
      pressure (PCWP) and cardiac index (CI) were determined. In addition, circulating
      concentrations of neurohumoral factors were determined at each time point. HR did
      not change following EECP treatment. However, RAP and PCWP increased
      significantly and CI was significantly elevated during EECP and thereafter. Blood
      atrial natriuretic peptide (ANP) concentration was significantly increased 15 and
      60 min after the start of EECP treatment, but brain natriuretic peptide (BNP) did
      not change. Renin, aldosterone and catecholamine concentrations also did not
      change. CONCLUSION: Treatment with EECP resulted in an increased preload because
      of increased venous return, and CI was increased thereafter. In patients with
      AMI, EECP increased blood ANP concentration, but not BNP, which suggests that an
      increase in ANP without an increase in BNP is an important mechanism for the
      effects of EECP treatment.

PMID- 15502385
TI  - Acute effects of diltiazem on regional left ventricular diastolic filling
      dynamics in patients with hypertrophic cardiomyopathy as assessed by color
      kinesis.
AB  - BACKGROUND: The effect of calcium antagonists on regional left ventricular (LV)
      filling dynamics in patients with hypertrophic cardiomyopathy (HCM) is not well
      known, so the present study evaluated the results of echocardiography with color
      kinesis (CK) analysis during diltiazem infusion. METHODS AND RESULTS: Nineteen
      patients (16 men, 3 women; mean age 55+/-15 years) underwent echocardiography
      with CK analysis during intravenous diltiazem (10 mg/2 min). Using the
      quantitative CK software the LV short-axis image was divided into 6 segments and
      the percent endocardial expansion at the early, mid- and late-diastolic filling
      time was averaged for all segments, with the standard deviation of the mean used
      as an index of diastolic asynchrony (asynchrony index). The regional mean filling
      time was also measured for the corresponding segments. As global diastolic
      parameters, the global filling time, peak filling rate, and the time-to-peak
      filling were calculated. After the administration of diltiazem, the asynchrony
      index was decreased for all three diastolic filling times. Diltiazem shortened
      the mean filling time overall, especially in the posterior and lateral wall
      segments. These findings were associated with significant improvement in the CK
      derived global diastolic parameters. CONCLUSIONS: Diltiazam has a favorable
      effect on LV diastolic asynchrony, which may account for the acute changes in
      global LV relaxation.

PMID- 15502386
TI  - Prolonged activation of hemostatic markers following conversion of atrial flutter
      to sinus rhythm.
AB  - BACKGROUND: It remains controversial whether prophylactic anticoagulation for
      embolism is required in patients with atrial flutter (AFL) prior to and following
      cardioversion as in patients with atrial fibrillation. To evaluate the potential
      prothrombotic state following cardioversion of AFL, concentrations of hemostatic
      markers were determined before and after conversion to sinus rhythm (SR). METHODS
      AND RESULTS: In 12 patients (mean age 68 years) with AFL who underwent
      transesophageal echocardiography in the plasma concentrations of markers for
      platelet activity (platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG)),
      thrombotic status (thrombin-antithrombin III complex (TAT) and prothrombin
      fragments 1 and 2 (F1+2)) and fibrinolytic status (D-dimer and plasmin-alpha(2)
      plasmin inhibitor complex (PIC)) were determined during AFL, and 3 days and 7
      days after restoration of SR. Left atrial appendage (LAA) blood flow velocity was
      lower immediately after than before restoration of SR (29+/-11 vs 41+/-23 cm/s,
      p<0.05). Three patients developed left atrial spontaneous echo contrast
      immediately after restoration of SR. Although the concentrations of the markers
      of platelet activity did not change after restoration of SR, those of TAT and PIC
      increased 7 days after restoration of SR as compared with during AFL (p<0.05).
      CONCLUSIONS: AFL patients have a potential risk for thromboembolism after
      restoration of SR and therefore anticoagulation might be required in selected
      patients.

PMID- 15502387
TI  - Evaluation of coronary artery remodeling in patients with acute coronary syndrome
      and stable angina by multislice computed tomography.
AB  - BACKGROUND: Multislice computed tomography (MSCT) was used to evaluate coronary
      artery remodeling in patients with acute coronary syndrome (ACS) and stable
      angina (SA). METHODS AND RESULTS: MSCT was performed in 31 patients with ACS and
      26 patients with SA and intravascular ultrasound (IVUS) was performed in 28 of
      these 57 patients. In both the MSCT and IVUS analyses, coronary artery remodeling
      was assessed by the remodeling index (RI): RI >1.10 was defined as positive
      coronary artery remodeling (PCAR) and RI <0.95 was defined as negative coronary
      artery remodeling (NCAR). The RI assessed by MSCT closely correlated with that of
      IVUS (r=0.86, n=28). The vessel area at the region of maximum luminal narrowing
      was also comparable between the MSCT and IVUS measurements (r=0.92). PCAR was
      present in 19 patients (61.3%) with ACS, but in none of the patients with SA
      (p<0.0001). However, NCAR was present in only 1 patient with ACS (3.2%), but was
      present in 18 patients (62.9%) with SA. The RI was significantly larger in
      patients with ACS (1.19+/-0.18) than in those with SA (0.89+/-0.10, p<0.0001).
      CONCLUSION: MSCT accurately assesses coronary artery remodeling.

PMID- 15502388
TI  - Serial alterations of beta-adrenergic signaling in dilated cardiomyopathic
      hamsters: possible role of myocardial oxidative stress.
AB  - BACKGROUND: The relationship between enhanced myocardial oxidative stress and
      impaired beta-adrenergic signaling remains to be characterized during the
      development of dilated cardiomyopathy. METHODS AND RESULTS: Alterations in
      myocardial oxidative stress and beta-adrenergic signaling, as well as left
      ventricular (LV) functional and structural changes, were evaluated during the
      development of cardiomyopathy in TO-2 hamsters; F1B hamsters served as controls.
      LV dysfunction was first apparent at 8 weeks of age and deteriorated thereafter
      in the TO-2 hamsters. At 32 weeks, the animals exhibited heart failure with an
      increased plasma norepinephrine concentration. Cardiac myolysis, as demonstrated
      by elevated plasma concentration of cardiac troponin T, peaked at 8 weeks. The
      glutathione redox ratio revealed increased oxidative stress in the LV myocardium
      in TO-2 hamsters even at 4 weeks and became manifest after 8 weeks. The hearts of
      TO-2 hamsters had significantly reduced superoxide dismutase activity from 8
      weeks onward compared with control hamsters. However, glutathione peroxidase
      activity was unchanged at any time point. The LV functional response to
      isoproterenol was markedly reduced at 8 weeks, without any apparent changes in
      the amount of beta-adrenergic signaling molecules, and it deteriorated
      thereafter. Adenylyl cyclase activity was significantly decreased, despite
      increased amounts of both G(s) alpha mRNA and protein, in the LV myocardium at 18
      weeks. CONCLUSIONS: Myocardial oxidative stress is actually enhanced in the
      initial development of LV dysfunction. Both activation of myocardial oxidative
      stress and impairment of beta-adrenergic signaling become prominent at the stage
      of severe LV dysfunction. Myocardial oxidative stress may be involved in the
      development of beta-adrenergic desensitization.

PMID- 15502389
TI  - Pitavastatin, a potent hydroxymethylglutaryl coenzyme a reductase inhibitor,
      increases cholesterol 7 alpha-hydroxylase gene expression in HepG2 cells.
AB  - BACKGROUND: The effect of pitavastatin on the mRNA levels of apolipoprotein (apo)
      A-I, peroxisome proliferator-activated receptor alpha (PPARalpha), cholesterol
      7alpha-hydroxylase (CYP7A1), and farnesoid X receptor (FXR) in HepG2 cells was
      examined to establish whether pitavastatin affects bile acid synthesis and if so,
      to determine a possible molecular mechanism. METHODS AND RESULTS: HepG2 cells
      were cultured in serum-free Dulbecco's modified Eagle medium for 18 h before drug
      treatment. Total RNA was extracted at set times and mRNA levels were quantified
      by reverse transcription-real time polymerase chain reaction. Pitavastatin at
      0.1, 1, 5, and 10 micromol/L increased the mRNA levels of apo A-I, PPARalpha,
      CYP7A1, and FXR in a dose-dependent manner. The mRNA levels of apo A-I, PPAR
      alpha, CYP7A1, and FXR similarly increased with increasing doses of pitavastatin.
      Coincubation of mevalonate (4 mmol/L) with pitavastatin (5 micromol/L) reversed
      the inductive effects of pitavastatin on the mRNA levels of these genes,
      indicating that the inductive effects of pitavastatin were related to its
      inhibition of HMG-CoA reductase. CONCLUSIONS: Pitavastatin increased the mRNA
      levels of CYP7A1 in HepG2 cells, suggesting that increased conversion of
      cholesterol to bile acids may be the mechanism for its potent low-density
      lipoprotein cholesterol-lowering effects.

PMID- 15502390
TI  - Contribution of vascular NAD(P)H oxidase to endothelial dysfunction in heart
      failure and the therapeutic effects of HMG-CoA reductase inhibitor.
AB  - BACKGROUND: The vascular NAD(P)H oxidase-derived superoxide anion (O(2)-) plays a
      crucial role in the pathological progression of hypertension and atherosclerosis,
      and HMG-CoA reductase inhibitors (statins) have vascular antioxidant effects.
      However, it is unclear whether the vascular NAD(P)H oxidase is involved in the
      endothelial dysfunction of congestive heart failure (CHF) and whether HMG-CoA
      reductase inhibitors (statins) exert their vasoprotective effects in CHF. The
      present study examined both the involvement of vascular NAD(P)H oxidase in
      endothelial dysfunction in dogs with tachycardia-induced CHF and the therapeutic
      effect of a statin (pitavastatin). METHODS AND RESULTS: Femoral blood flow (FBF)
      responses to acetylcholine was significantly impaired in the CHF group, but were
      improved by pitavastatin. Vascular O(2)- production, NAD(P)H oxidase activity and
      Nox4 and p47phox expression were significantly elevated in CHF compared with the
      normal group. The elevated O(2)-production in the CHF group was suppressed by the
      NAD(P)H oxidase inhibitor, apocynin, to the normal level. In contrast, neither
      the gene expression nor the activity of endothelial nitric oxide synthase (eNOS)
      differed significantly between the normal and CHF groups. However, pitavastatin
      significantly suppressed O(2)- production, NAD(P)H oxidase activity and Nox4 and
      p47phox expression and increased eNOS expression and activity compared with the
      CHF group. CONCLUSIONS: The activated vascular NAD(P)H oxidase contributes to
      endothelial dysfunction in CHF, which was partly improved by pitavastatin via its
      inhibition of NAD(P)H oxidase.

PMID- 15502391
TI  - Ampulla ('takotsubo') cardiomyopathy of both ventricles: evaluation of
      microcirculation disturbance using 99mTc-tetrofosmin myocardial single photon
      emission computed tomography and doppler guide wire.
AB  - An 84-year-old woman was admitted to hospital with chest pain at rest. An
      electrocardiogram showed ST-segment elevation in leads II, III, aV(F) and V(2-6),
      and the 2-dimension echocardiogram showed apical ballooning akinesis and basal
      hyperkinesis of both ventricles. (99m)Tc-tetrofosmin myocardial single photon
      emission computed tomography (SPECT) showed severely reduced uptake in the apex.
      Coronary angiography did not show any organic stenosis, and epicardial coronary
      spasm was not provoked by the ergonovine loading test. Left ventriculography
      showed apical ballooning akinesis and basal hyperkinesis, which were also
      apparent on right ventriculography. The coronary flow velocity pattern showed
      rapid diastolic acceleration and deceleration times, and the coronary flow
      reserve measured with a Doppler guide wire was severely decreased. (99m)Tc
      tetrofosmin myocardial SPECT showed improvement in the findings after 14 days,
      and the coronary flow velocity pattern and coronary flow reserve improved after
      30 days. Left and right ventriculography both revealed mild improvement in the
      wall motion. These findings suggested that a microcirculation disturbance caused
      ampulla ('Takotsubo') cardiomyopathy.

PMID- 15502392
TI  - Transient left ventricular apical ballooning in a patient with bicuspid aortic
      valve created a left ventricular thrombus leading to acute renal infarction.
AB  - A 44-year-old woman had tako-tsubo-like ventricular dysfunction with chest pain
      and ST segment elevation on the ECG. Echocardiography revealed a bicuspid aortic
      valve with moderate to severe aortic regurgitation. She developed mild heart
      failure during the clinical course, but the medication (furosemide, enalapril,
      and asprin) had to be stopped because of skin eruptions. Four weeks after ceasing
      the antiplatelet agent, she was re-admitted with acute renal infarction. Enhanced
      chest computed tomography revealed a filling defect in the left ventricle and
      echocardiography showed a high echogenic mass in the left ventricular apical
      wall. These findings strongly suggested that the renal infarction was caused by
      an embolism derived from a left ventricular thrombus that formed during the
      clinical course of the transient left ventricular apical ballooning.
      Anticoagulation therapy with urokinase and warfarin successfully lysed the
      thrombus. Left ventricular thrombus should be considered a complication of
      transient left ventricular apical ballooning, especially in patients with organic
      heart disease.

PMID- 15502393
TI  - Failure of disopyramide to improve right ventricular outflow tract obstruction
      after living-donor lobar lung transplantation.
AB  - Right ventricular (RV) outflow tract obstruction (RVOTO) is an uncommon
      complication of lung transplantation in patients with pulmonary hypertension (PH)
      and both medical management and surgical intervention are required. A 28-year-old
      female with primary PH was referred and because she did not respond to medical
      treatment, living-donor lobar lung transplantation was performed. The operation
      was successful, but dyspnea and exercise intolerance developed during
      rehabilitation and transthoracic echocardiography revealed RVOTO. Intravenous
      disopyramide during cardiac catheterization reduced the pressure gradient from 35
      mmHg to 16 mmHg without decreasing RV systolic pressure. However, electrical and
      hemodynamic parameters were adversely affected by disopyramide and thus, after
      cardiac catheterization, administration of fluid and a low dose of atenolol was
      started, and her symptoms improved. Transthoracic echocardiography showed
      improvement in the RVOTO. This case suggests that disopyramide should be avoided
      for patients with RVOTO following lung transplantation and that other negative
      inotropic agents, such as beta-blockers, are more effective for relief of RVOTO.

PMID- 15502394
TI  - Novel technique using intravascular ultrasound-guided guidewire cross in coronary
      intervention for uncrossable chronic total occlusions.
AB  - The experience of using a novel application of intravascular ultrasound (IVUS)
      guided percutaneous coronary interventions for chronic total occlusions is
      reported in 2 cases. In the first case, an IVUS catheter was advanced into a side
      branch to identify the entry point of the major branch. In the second case, IVUS
      guided penetration of the guidewire from the false lumen to the true lumen after
      causing a dissection was successful.

PMID- 15502395
TI  - [A new mechanosensitive channel SAKCA and a new MS channel blocker GsTMx-4].
AB  - Cells can respond to a variety of mechanical stimuli such as tension, pressure,
      and shear stress. However, the mechanisms of mechanotransduction are largely
      unknown. The major reason for this lies in the ambiguity of the molecular entity
      of cell mechanosensors. Currently only MS (mechanosensitive) channels conform to
      an established class of mechanosensors due to the firm and detailed analyses by
      electrophysiolgy. Although molecular structures of MS channels are known for
      limited members, higher order structures of bacterial MS channels have been
      resolved and their detailed structure-function studies are in progress. In
      contrast, molecular and biophysical analyses of eukaryote MS channels, which may
      attract much attention, are yet not well-studied. Although many candidate
      molecules have been proposed as the cell mechanosensor, currently only 2-pore
      domain K channels (TREK/TRAAK) and SAKCA, a new class of MS channel introduced
      here, may be the subjects eligible for rigorous electrophysiological analyses. On
      the other hand, lack of specific blockers to MS channels is another reason why
      the progress in this field is slow. Gadolinium (Gd(3+)) has been extensively used
      as a potent blocker of MS channels, but its nonspecific actions have limited its
      usefulness. Very recently, a promising 35 mer peptide, which can be more specific
      for MS channels, named GsMTx-4 has been isolated from spider venom. This peptide
      is interesting because it inhibits stretch-induced atrial fibrillation, which may
      involve MS channel activation and thus can be used as a basis for developing a
      new class of drugs to cure heart failure. This short review deals with recent
      progresses in MS channel studies and the structure-function of SAKCA, a recently
      cloned MS channel from heart, as well as its interaction with the new MS channel
      blocker GsMTx-4.

PMID- 15502396
TI  - [Crucial roles of PECAM-1 in shear stress sensing of vascular endothelial cells].
AB  - Fluid shear stress (FSS) induces many forms of responses, including
      phosphorylation of ERK in endothelial cells (ECs). We have earlier reported that
      FSS and hyper-osmotic shock rapidly induce tyrosine phosphorylation of PECAM-1
      (CD31). The phosphorylated PECAM-1 acts as a plasma membrane anchoring site for
      SHP2, a protein tyrosine phosphatase involved in the signal transmission from
      receptor tyrosine kinases to ERK. Osmotic shock also induces transient ERK
      activation in ECs. The osmotic-shock-induced ERK activation but not p38 MAP
      kinase activation was dependent on the PECAM-1 engagement and was blocked by its
      downregulation. When magnetic beads coated with antibodies against the
      extracellular domain of PECAM-1 were attached to ECs and tugged by magnetic
      force, PECAM-1 associated with the beads was tyrosine phosphorylated. ERK was
      also phosphorylated in these cells. Binding of the beads by itself or pulling on
      the cell surface using poly-L-lysine coated beads did not induce phosphorylation
      of PECAM-1 and ERK. These results suggest that PECAM-1 is a mechanotransduction
      molecule.

PMID- 15502397
TI  - [Shear-stress sensing via P2 purinoceptors in vascular endothelial cells].
AB  - The mechanisms by which shear stress elevates intracellular Ca(2+) in endothelial
      cells (EC) are not fully understood. Here we report that endogenously released
      ATP contributes to shear stress-induced Ca(2+) responses. Application of a flow
      of Hank's balanced solution to human pulmonary artery EC (HPAEC) elicited shear
      stress-dependent increases in Ca(2+) concentration. Chelation of extracellular
      Ca(2+) with EGTA completely abolished the Ca(2+) responses, whereas the
      phospholipase C inhibitor U-73122 and the Ca(2+)-ATPase inhibitor thapsigargin
      had no effect, indicating that the response was due to the influx of
      extracellular Ca(2+). The Ca(2+) influx was significantly suppressed by apyrase,
      which degrades ATP, and by antisense oligonucleotide targeted to P2X4 receptors.
      A luciferase luminometric assay showed that shear stress induced dose-dependent
      release of ATP. When the ATP release was inhibited by the ATP synthase inhibitors
      angiostatin or oligomycin, the Ca(2+) influx was markedly suppressed but was
      restored by removal of these inhibitors or addition of extracellular ATP. These
      results suggest that shear stress stimulates HPAEC to release ATP, which
      activates Ca(2+) influx via P2X4 receptors.

PMID- 15502398
TI  - [Role of lysophosphatidic acid as a mechanosensitizer].
AB  - The mechanotransduction mechanisms play an important role in regulation of
      specific cellular response or maintenance of cellular homeostasis in a wide
      variety of cell types. Increase in intracellular free Ca(2+) concentration
      ([Ca(2+)](i)) is an important signal in the first step of mechanotransduction.
      Mechanosensitive (MS) cation channels are thought to be a putative pathway of
      Ca(2+) entry; however, the molecular mechanisms remain unclear. We have
      previously demonstrated that lysophosphatidic acid (LPA), a bioactive
      phospholipid present in human plasma, sensitizes the response of [Ca(2+)](i) to
      mechanical stress in cultured smooth muscle cells, cultured lung epithelial
      cells, and cultured lens epithelial cells. Using real-time confocal microscopy,
      local increases in [Ca(2+)](i) in several regions within the cell subjected to
      mechanical stress were clearly visualized in cultured bovine lens epithelial
      cells and cultured vascular endothelial cells in the presence of LPA. We called
      the phenomenon "Ca(2+) spots". Pharmacological studies revealed that the Ca(2+)
      spot is an elementary Ca(2+)-influx event through MS channels. In this review,
      possible physiological and pathophysiological roles of LPA as a mechanosensitizer
      are discussed.

PMID- 15502399
TI  - [Mechanical stretching inhibits adipocyte differentiation of 3T3-L1 cells: the
      molecular mechanism and pharmacological regulation].
AB  - Obesity frequently promotes a variety of cardiovascular diseases including
      atherosclerosis, hypertension, and type 2 diabetes. In a view of both the
      preventive and therapeutic aspects of the abovementioned diseases, most intensive
      clinical interventions have been primarily directed at decreasing excessive
      amounts of fat tissue by a change in the balance between intake and expenditure
      of energy; such changes are typically effected via daily exercise and diet
      control. Mechanical stimuli such as stretching and rubbing of fat tissues using
      gymnastic exercises or massage are believed to decrease obesity; however, there
      is no report concerning the direct effect of the mechanical stimulation on
      adipocytes. Here, we demonstrated that cyclic stretch inhibited adipocyte
      differentiation of mouse 3T3-L1 cells, which was attributable to a reduced
      expression of adipogenic transcription factor peroxisome proliferator-activated
      receptor (PPAR)gamma(2) via the activation of an extracellular signal-regulated
      protein kinase (ERK) pathway. The inhibitory effect of the cyclic stretching on
      the differentiation of 3T3-L1 cells could be restored by troglitazone, a
      synthetic ligand for PPARgamma. Our results provide a molecular basis for the
      physiological significance of the local application of mechanical stimuli to fat
      tissues, which is totally independent of a mechanism for systemic energy
      consumption.

PMID- 15502400
TI  - [Methods for preparation and functional analysis of islet beta-cells].
AB  - Regulation of blood glucose is a fundamental homeostasis in the body. Insulin is
      released from pancreatic beta-cells in response to changes in blood glucose, the
      defect of which leads to impaired insulin secretion and diabetes mellitus.
      Pancreatic beta-cells that release insulin occupy approximately 70% of the islet
      cells, while alpha, delta, PP-cells are also present in islets. Therefore,
      analysis of beta-cells is a direct approach for studying mechanisms of insulin
      secretion. Insulin secretion is regulated by cytosolic Ca(2+) in beta-cells, and
      its concentration and localization can be measured in real time by fluorescence
      imaging using indicators. Glucose metabolism is assessed by measurements of
      NAD(P)H by its autofluorescence. Furthermore, beta-cells are equipped with ion
      channels, which transduce glucose-evoked metabolic signals to electric signals.
      Electrophysiological analysis by patch clamp techniques detects the activity of
      various ion channels and membrane potential. Several beta-cell lines including
      HIT, MIN6, INS1, RIN, and beta TC are used; however, they do not necessarily
      retain normal responsiveness to glucose. Therefore, analysis of physiologic
      functions of beta-cells requires the use of acutely isolated or primary cultured
      beta-cells from normal animals. The methods for preparation of islets and single
      beta-cells using collagenase can be applied to a variety of animals of small to
      large sizes, which can produce islets and beta-cells with physiological
      responsiveness to glucose. These primary cultured beta-cells can be used for
      elucidating signal transduction mechanisms, and evaluating effects of drugs,
      providing excellent tools for physiological, pharmacological, and disease
      oriented studies.

PMID- 15502401
TI  - Functional hypophysectomy simply by neck-strangulation in the rat: applications
      for ACTH and LH assays.
AB  - The classical methods for hypophysectomy require a long training-period and at
      the end of each experiment, it is required to check any undue remnant of the
      hypophyseal tissue in the sella turcica, and there must be exclusion of such
      datum with the remnant from the experimental group. The present method for
      functional hypophysectomy by neck-strangulation in the rat is very simple to
      perform so that even an experimenter with little experience can become easily
      accustomed to the technique and obtain a number of functionally hypophysectomized
      preparations at any time he intends, with no need to check the remnant. The
      cerebral blood circulation of vertebrally dislocated rats was immediately
      intercepted by means of neck-strangulation and artificially respired. Fifteen
      minutes after intravenous injection of ACTH (0.1 - 3.2 mU/rat) or LH (312.5 -
      2500 ng/rat), blood was sampled from the vena cava, and sera were examined for
      corticosterone or testosterone by radioimmunoassay. A linear dose-response
      relationship was obtained within a dose range of 0.2 - 1.6 mU/rat of ACTH and
      312.5 - 1250 ng/rat of LH. In the ACTH assay, parapharyngeally hypophysectomized
      rats were compared. It was found that the sensitivity of functionally
      hypophysectomized preparations was 2.72 times higher than that of the
      parapharyngeally hypophysectomized rats.

PMID- 15502402
TI  - Inhibition mechanism of Gosha-jinki-gan on the micturition reflex in rats.
AB  - We investigated the actions of Gosha-jinki-gan, a traditional Japanese medicine
      containing processed Aconiti tubers, on urinary bladder function in anesthetized
      rats. In cystometrical investigations, Gosha-jinki-gan (1.0 g/kg, i.d.) increased
      bladder capacity as well as micturition threshold pressure. In addition, it
      decreased the frequency of distension-induced rhythmic bladder contractions.
      However, it did not influence the amplitude of bladder contractions induced by
      electrical stimulation of the pontine micturition center. The inhibitory effect
      of Gosha-jinki-gan on bladder motility was abolished by pretreatment with nor
      binaltorphimine (10 mg/kg, s.c.), and was diminished by the concomitant use of
      anti-dynorphin A antiserum (10 microg, i.t.), yohimbine (10 microg, i.t.), or
      methysergide (20 microg, i.t.). Processed Aconiti tuber extract (27 mg/kg, i.d.)
      also suppressed bladder motility, and the effect was abolished by nor
      binaltorphimine. These results suggest that Gosha-jinki-gan attenuates bladder
      sensation via the kappa-opioid receptor-stimulating action of processed Aconiti
      tuber. Gosha-jinki-gan may be a useful anti-pollakiuria agent that does not
      influence bladder contractility at micturition.

PMID- 15502403
TI  - Amino-acid residues involved in the expression of the activity of Escherichia
      coli TolC.
AB  - The Escherichia coli TolC, composed of 471 amino-acid residues, functions as a
      channel tunnel in the transport of various molecules across the outer membrane.
      We found previously that Leu-412, the 60th amino-acid residue from the carboxy
      terminal end, was crucial to the transport activity of TolC. Leu-412 is located
      in a domain which protrudes from the main body of TolC into the periplasm.
      Subsequent study indicated that the hydrophobicity generated by Leu-412 played an
      important role in the activity of TolC (H. Yamanaka, T. Nomura, N. Morisada, S.
      Shinoda, and K. Okamoto, Microb. Pathog. 33: 81-89, 2002). We predicted that
      other hydrophobic amino-acid residues around Leu-412 were also involved in the
      expression of the activity of TolC. To test this possibility, we substituted
      several hydrophobic residues around Leu-412, (Leu-3, Val-6, Leu-212, Leu-213, Leu
      223, and Leu-224), with serine and examined the activity of these mutant TolCs.
      The result showed that Leu-3 is involved in the activity of TolC, but the other
      residues are not. The involvement of Leu-3 was confirmed by the residue deletion
      experiment. A subsequent point-mutational analysis of the residue showed that a
      hydrophobic side chain is required at position 3 for TolC to express its
      activity. As the distance between the alpha-carbons of Leu-3 and Leu-412 is just
      7.45 angstroms, hydrophobic interaction between the two leucine residues might be
      involved in the activity of TolC.

PMID- 15502404
TI  - Identification and characterization of the pswP gene required for the parallel
      production of prodigiosin and serrawettin W1 in Serratia marcescens.
AB  - Serratia marcescens mutants defective in production of the red pigment
      prodigiosin and the biosurfactant serrawettin W1 in parallel were isolated by
      transposon mutagenesis of strain 274. Cloning of the DNA fragment required for
      production of these secondary metabolites with different chemical structures
      pointed out a novel open reading frame (ORF) named pswP. The putative product
      PswP (230 aa) has the distinct signature sequence consensus among members of
      phosphopantetheinyl transferase (PPTase) which phosphopantetheinylates peptidyl
      carrier protein (PCP) mostly integrated in the nonribosomal peptide synthetases
      (NRPSs) system. Since serrawettin W1 belongs to the cyclodepsipeptides, which are
      biosynthesized through the NRPSs system, and one pyrrole ring in prodigiosin has
      been reported as a derivative of L -proline tethered to phosphopantetheinylated
      PCP, the mutation in the single gene pswP seems responsible for parallel failure
      in production of prodigiosin and serrawettin W1.

PMID- 15502405
TI  - Piceatannol prevents lipopolysaccharide (LPS)-induced nitric oxide (NO)
      production and nuclear factor (NF)-kappaB activation by inhibiting IkappaB kinase
      (IKK).
AB  - The effect of piceatannol on lipopolysaccharide (LPS)-induced nitric oxide (NO)
      production was examined. Piceatannol significantly inhibited NO production in LPS
      stimulated RAW 264.7 cells. The inhibition was due to the reduced expression of
      an inducible isoform of NO synthase (iNOS). The inhibitory effect of piceatannol
      was mediated by down-regulation of LPS-induced nuclear factor (NF)-kappaB
      activation, but not by its cytotoxic action. Piceatannol inhibited IkappaB kinase
      (IKK)-alpha and beta phosphorylation, and subsequently IkappaB-alpha
      phosphorylation in LPS-stimulated RAW 264.7 cells. On the other hand, piceatannol
      did not affect activation of mitogen-activated protein (MAP) kinases including
      extracellular signal regulated kinase 1/2 (Erk1/2), p38 and stress-activated
      protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK). Piceatannol inhibited the
      phosphorylation of Akt and Raf-1 molecules, which regulated the activation of IKK
      alpha and beta phosphorylation. The detailed mechanism of the inhibition of LPS
      induced NO production by piceatannol is discussed.

PMID- 15502406
TI  - Characterization of Ehrlichia species from Ixodes ovatus ticks at the foot of Mt.
      Fuji, Japan.
AB  - A total of 390 adult ticks (288 Ixodes ovatus and 102 I. persulcatus ) collected
      at the foot of Mt. Fuji and two near cities in Shizuoka prefecture, Japan, were
      examined for Ehrlichia infection by isolation with laboratory mice from whole
      tick tissues. Ehrlichial DNAs were detected from the spleens of mice inoculated
      with tissues from I. ovatus, but not I. persulcatus. The prevalence of ehrlichiae
      in the ticks was estimated to be ca. 3%. The 16S rDNA analysis revealed that the
      sequences of 8 ehrlichial isolates (termed "Shizuoka" isolates) obtained were
      identical, and they were very similar, but not identical, to those of two
      Ehrlichia species strain variants recently isolated in Japan, followed by
      Ehrlichia chaffeensis in the US. Analysis of parts of the omp-1 multigene family
      specific for monocytic ehrlichiosis agents showed that the Shizuoka isolates were
      distinct from other ehrlichial organisms. The Shizuoka isolates caused death in
      immunocompetent laboratory mice, suggesting that they are highly pathogenic in
      mice. The data show that the Shizuoka isolates are likely to be a new strain
      variant of Ehrlichia species in Japan. Further characterization and surveillance
      will be required in Japan due to the presence of these human ehrlichiosis agent
      like organisms.

PMID- 15502407
TI  - Comparative evaluation of standard dilution method and commercial kit for frozen
      plate antifungal susceptibility testing of yeasts using 200 clinical isolates.
AB  - A comparative evaluation of standard microdilution methods and a commercial kit
      for frozen plate antifungal susceptibility testing of yeasts was performed using
      amphotericin B, flucytosine, fluconazole, miconazole, and itraconazole on 200
      yeast isolates. The isolates included 100 strains of Candida albicans, eight of
      C. tropicalis, twelve of C. parapsilosis, eight of C. glabrata, five of
      Cryptococcus neoformans, thirteen of Trichosporon asahii, and 54 other strains of
      seven other species of ascomycotic yeasts. Microdilution testing was performed
      according to the standard method for antifungal susceptibility testing published
      by the Japanese Society for Medical Mycology (JSMM), which are a modification of
      the method developed by the National Committee for Clinical Laboratory Standards
      (NCCLS) M27-P. The commercial kit was prepared according to the manufacturer's
      instructions. The degree of agreement within +/-1 dilution for 200 clinical
      isolates against five antifungal agents was excellent with values for
      amphotericin B, flucytosine, fluconazole, miconazole, and itraconazole of 100%,
      99.0%, 97.5%, 97.0%, and 97.0%, respectively. Overall, the frozen plate
      antifungal susceptibility testing kit provided convenient and reproducible
      results comparable to those obtained with the JSMM standard method.

PMID- 15502408
TI  - Genotype analysis of Malassezia restricta as the major cutaneous flora in
      patients with atopic dermatitis and healthy subjects.
AB  - Lipophilic yeasts of the genus Malassezia colonize the skin surface of humans and
      are an exacerbating factor in atopic dermatitis (AD). Two species, M. restricta
      and M. globosa are major cutaneous microflora in both AD patients and healthy
      subjects. We compared the DNA sequences of the intergenic spacer (IGS) region,
      located between the 26S and 5S rRNA genes of M. restricta colonizing the skin
      surfaces of 13 AD patients and 12 healthy subjects, and of three CBS stock
      strains as references. The IGS 1 sequences were divided into two major groups,
      corresponding to AD patients and healthy subjects. These findings suggest that a
      specific genotype of M. restricta plays a significant role in AD, although M.
      restricta commonly colonizes both AD patients and healthy subjects.

PMID- 15502409
TI  - Fluconazole-resistant pathogens Candida inconspicua and C. norvegensis: DNA
      sequence diversity of the rRNA intergenic spacer region, antifungal drug
      susceptibility, and extracellular enzyme production.
AB  - The opportunistic fungal pathogens Candida inconspicua and C. norvegensis are
      very rarely isolated from patients and are resistant to fluconazole. We collected
      38 strains of the two microorganisms isolated from Europe and Japan, and compared
      the polymorphism of the rRNA intergenic spacer (IGS) and internal transcribed
      spacer (ITS) regions, antifungal drug susceptibility, and extracellular enzyme
      production as a potential virulence factor. While the IGS sequences of C.
      norvegensis were not very divergent (more than 96.7% sequence similarity among
      the strains), those of C. inconspicua showed remarkable diversity, and were
      divided into four genotypes with three subtypes. In the ITS region, no variation
      was found in either species. Since the sequence similarity of the two species is
      approximately 70% at the ITS region, they are closely related phylogenetically.
      Fluconazole resistance was reconfirmed for the two microorganisms but they were
      susceptible to micafungin and amphotericin B. No strain of either species
      secreted aspartyl proteinase or phospholipase B. These results provide basal
      information for accurate identification, which is of benefit to global molecular
      epidemiological studies and facilitates our understanding of the medical
      mycological characteristics of C. inconspicua and C. norvegensis.

PMID- 15502410
TI  - Delayed HIV-1 infection of CD4+ T lymphocytes from therapy-naive patients
      demonstrated by quantification of HIV-1 DNA copy numbers.
AB  - Measuring the amount of HIV-1 DNA in infected cells is important to estimate the
      size of the viral reservoir in patients. However, the clinical impact of the
      intracellular viral DNA level remains unclear. The present study examines the
      clinical significance of the HIV-1 DNA level in peripheral CD4+ T lymphocytes
      from 21 therapy-naive patients. HIV-1 DNA levels in purified peripheral CD4+ T
      lymphocytes were measured by the real-time PCR method using the Roche LightCycler
      system that can detect 200 copies/10(6) cells. We detected intracellular HIV-1
      DNA in 15 (71.4%) of 21 patients at levels ranging from 270 to 98,120
      copies/10(6) CD4+ cells, with a median of 2,220 copies/10(6) cells. We also found
      HIV-1 DNA that was below the detection limit in the remaining 6 patients,
      although 8,800-150,000 copies/ml of HIV-1 RNA were detected in plasma. Circular
      HIV-1 DNA was not detected in 5 of 6 cases, suggesting that reverse transcription
      in CD4+ T lymphocytes of these cases was not active. Thus, delayed HIV-1
      infection of CD4+ T lymphocytes was demonstrated in these patients. The level of
      HIV-1 DNA in peripheral CD4+ T lymphocytes indicates the clinical status of
      therapy-naive patients.

PMID- 15502411
TI  - Variation of toxigenic Vibrio cholerae O1 in the aquatic environment of
      Bangladesh and its correlation with the clinical strains.
AB  - The diversity of toxigenic V. cholerae O1 in the aquatic environment of
      Bangladesh is not known. A total of 18 environmental and 18 clinical strains of
      toxigenic V. cholerae O1 were isolated simultaneously from four different
      geographical areas and tested for variation by the pulsed-field gel
      electrophoresis method. Environmental strains showed diversified profiles and one
      of the profiles was common to some environmental strains and most clinical
      strains. It appears that one clone has an advantage over others to cause disease.
      These findings suggest that the study of the molecular ecology of V. cholerae O1
      in relation to its environmental reservoir is important in identifying virulent
      strains that cause disease.

PMID- 15502412
TI  - Consideration of cysteine protease activity for serological M-typing of clinical
      Streptococcus pyogenes isolates.
AB  - Clinical isolates of Streptococcus pyogenes were classified by serological typing
      of their surface M protein. Non-M typeable strains with the emm1 gene were
      characterized as the degradation of M protein caused by overproduction of the
      extracellular cysteine protease, SpeB. These events are dependent on the growth
      phase. M protein produced prior to expression of SpeB is degraded in the
      stationary phase when the active form of SpeB is detected. The proteolytic
      degradation of M protein should be considered for precise M typing analysis.

PMID- 15502413
TI  - Acetate-mediated production of orotic acid by ura3 mutants of Candida albicans.
AB  - Candida albicans ura3 mutants were found to produce large amounts of orotic acid
      when the growth medium was supplemented with sodium acetate. Experiments with 13C
      labeled acetate showed that the acetate served as a precursor of orotic acid.
      This system of acetate-mediated production of orotic acid is similar to other
      documented microbial producers in yield but unique for its acetate requirement.

PMID- 15502414
TI  - PCR-based identification of pandemic group Vibrio parahaemolyticus with a novel
      group-specific primer pair.
AB  - A PCR-based assay to identify pandemic group Vibrio parahaemolyticus has been
      developed. The assay employs an oligonucleotide primer pair derived from the
      group-specific sequence of an arbitrarily primed-PCR fragment, which is located
      in the genome encoding a "hypothetical protein," approximately 80% homologous to
      the Mn2+ and Fe2+ transporter of the NRAMP family of V. vulnificus. The assay
      distinguished the pandemic group from other V. parahaemolyticus strains by
      yielding a 235-bp specific amplicon, and can be a useful diagnostic tool for
      identification of pandemic group strains.

PMID- 15502415
TI  - Effects of smokeless tobacco "Maras powder" use on respiratory functions.
AB  - In Turkey, "Maras Powder," which is a kind of powder yielded from the shields of
      tobacco, is widely used as smokeless tobacco through buccal mucosa or together
      with cigarette. Maras powder, composed of ash and a plant named Nicotiana Rustica
      Linn, is sometimes used to give up smoking. The present study was aimed to
      investigate the effects of Maras powder use on respiratory functions of healthy
      subjects who do not have any chronic disease. We found statistically significant
      differences in percentage of forced expiratory volume in the first second
      (FEV(1)%) (p = 0.001), the ratio of FEV(1) to forced vital capacity (FEV(1)/FVC)
      (p = 0.024), percent of maximum expiratory flow rate (FEF(25-75)%) (p = 0.002)
      and percent of peak expiratory flow (PEF%) (p = 0.037) between cigarette smokers
      with Maras powder use (n = 23) and control subjects (n = 24). Likewise, when
      cigarette smokers (n = 24) and control subjects were compared, the differences
      for all these parameters were significant (p = 0.022, p = 0.048, p = 0.011 and p
      = 0.047, respectively). Only FEV(1)% and FEF(25-75)% were significantly lower in
      cigarette smokers with Maras powder use than in Maras powder users (n = 28) (p =
      0.011 and p = 0.022, respectively). There was a negative correlation between
      forced vital capacity and Maras powder use (r = -0.315, p = 0.03). The present
      study suggests that Maras powder does not cause serious bronchial obstruction.
      This may be due to usage of the smokeless tobacco through buccal mucosa but not
      through inhalation as in case of cigarette smoking.

PMID- 15502416
TI  - The effect of fasting month of Ramadan on the abdominal fat distribution:
      assessment by computed tomography.
AB  - The aim of this study was to evaluate the changes in abdominal fat distribution
      in the fasting month of Ramadan. Thirty-eight healthy volunteers (17 women and 21
      men) who fasted in the month of Ramadan in 2002 were included in this prospective
      study. Waist, hip and thigh circumferences, weight and height of all subjects
      were measured. Waist-to-hip ratio (WHR), waist-to-thigh ratio (WTR) and body mass
      index (BMI) were calculated for each subject. For assessing the fat distribution
      in the abdomen, computed tomography (CT) was performed. Both subcutaneous and
      visceral fat areas were calculated by the CT scanning technique. All of the
      calculations were done before (first measurement) and after (second measurement)
      Ramadan fasting and the changes were evaluated. No statistically significant
      differences were found in all subjects between the first and second measurements,
      which include total, subcutaneous and visceral fat areas, waist, hip and thigh
      circumferences, weight, BMI, WHR, and WTR (p > 0.05). In females and the
      individuals in their twenties, there was a significant decrease in visceral fat
      area (p < 0.05). Despite of the general opinion that supposes the change of
      weight during the fasting month of Ramadan, there were no significant differences
      in weight and abdominal fat distribution. However in female and young
      individuals, there was a reduction in visceral fat compartment. This could be due
      to fat redistribution, because they have more physical activity than males and
      older individuals.

PMID- 15502417
TI  - The efficacy of a hyaluronate/carboxymethylcellulose membrane in prevention of
      postoperative adhesion in a rat uterine horn model.
AB  - The current study was designed to investigate the efficacy of a
      hyaluronate/carboxymethylcellulose membrane for the prevention of post-operative
      adhesion in a rat uterine horn model. This is a prospective double-blinded
      controlled study. Nineteen injured uterine horns were treated with a
      hyaluronate/carboxymethylcellulose membrane as a barrier and 19 injured uterine
      horns without any treatment served as a control group. Two weeks later, second
      look laparotomies were performed in order to assess the degree of the adhesion.
      Total adhesion scores, histopathological analysis of inflammation process and
      vascularization of adhesions were compared with control group. P values of 5% or
      less were considered statistically significant. Animals treated with a
      hyaluronate/carboxymethylcellulose membrane had significantly reduced post
      surgical adhesion scores when compared with control group. In histopathological
      examination, there was less vascularization in the treatment group. The types and
      extent of inflammation were similar in two groups. Clinically and
      histopathologically, a hyaluronate/carboxymethylcellulose membrane is effective
      in reducing postoperative adhesion formation in the rat uterine horn model.

PMID- 15502418
TI  - Expression of nuclear factor-kappa B and placental apoptosis in pregnancies
      complicated with intrauterine growth restriction and preeclampsia: an
      immunohistochemical study.
AB  - Preeclampsia affects 7-10% of all pregnancies, and is a major cause of maternal
      and fetal morbidity and mortality. Although enhanced apoptosis is well known in
      placentas with preeclampsia, the role of transcription factor nuclear factor
      kappa B (NF-kappa B) in the process is still being debated. In this work, we
      investigate the relationship between NF-kappa B expression and trophoblastic cell
      apoptosis in pregnancies complicated with preeclampsia or intrauterine growth
      restriction (IUGR) by immunohistochemical analysis of NF-kappa B and three
      apoptosis related markers: bcl-2, caspase-3, and M30 CytoDeath antibody that
      identifies early apoptotic changes in the cytoskeleton related to action of
      caspase. The study was conducted on placental samples from 19 preeclamptic, 5
      IUGR-complicated and 10 normal pregnant women. The three conclusions from the
      statistical analysis of the data are obtained; (i) Significantly higher
      expression of NF-kappa B in IUGR-complicated (p = 0.003) and preeclamptic
      placentas (p = 0.004) than the control placentas, (ii) significantly higher M30
      index and caspase 3 expression in IUGR and preeclampsia placentas (p = 0.003),
      and (iii) decreased expression of bcl-2 in IUGR and preeclampsia placentas (p =
      0.001). Based on these observations, we suggest that increased trophoblastic
      apoptosis is at least partially induced by NF-kappa B and reduced bcl-2
      expression.

PMID- 15502419
TI  - Intraocular pressure and quality of blockade in peribulbar anesthesia using
      ropivacaine or lidocaine with adrenaline: a double-blind randomized study.
AB  - The aim of this study was to compare the effects of ropivacaine with those of
      lidocaine on the intraocular pressure (IOP) and the quality of the blockade in
      peribulbar anesthesia for cataract surgery. Fifty patients were allocated
      randomly into two groups and received 7-10 ml of 0.75% ropivacaine or 2%
      lidocaine with adrenaline, though the peribulbar two-point injection. The quality
      of the blockade was assessed by ocular and eyelid akinesia, pain during the
      peribulbar injection, and surgical satisfaction. The duration of the motor block
      was also evaluated after surgery. The IOP was measured using a Tonopen before the
      blockade (control) and at 1, 5, and 10 min after injection of the anesthetic.
      Lidocaine induced significantly lower akinesia scores at 6, 8, and 10 min post
      injection than did ropivacaine. The mean IOP (mmHg) was significantly lower with
      respect to the baseline level at 10 min after blockade in the ropivacaine group
      compared with the lidocaine group. Ropivacaine also caused less pain on
      injection. There was no difference in surgical satisfaction between the groups.
      The duration of the motor block obtained with ropivacaine was longer than that
      obtained with lidocaine. Our data indicate that ropivacaine has efficacy similar
      to lidocaine, with slightly longer onset and duration of the motor blockade. In
      addition, ropivacaine (0.75%) induces lower IOP and less pain on injection than
      does lidocaine (2%) when used in peribulbar anesthesia for cataract surgery.

PMID- 15502420
TI  - Acute phase reactants in allergic airway disease.
AB  - Acute phase reactants have been implicated for their involvement as
      proinflammatory molecules in various inflammatory diseases. However, little is
      known regarding their role in the allergic airway disease. The aim of the present
      study was to examine the blood concentrations of three acute-phase proteins,
      namely C-reactive protein (CRP), serum amyloid A (SAA) and fibrinogen in patients
      with allergic rhinitis and asthma. Three study groups include: non-smoker
      allergic rhinitis (n = 50), non-smoker asthma (n = 20), and non-allergic, non
      smoker healthy control subjects (n = 20). Patients who have had recent upper or
      lower respiratory tract infection and trauma, any rheumatological illnesses,
      malignancy or obesity were excluded. Blood samples were obtained from all the
      patients and control subjects and were analyzed for serum CRP, SAA and plasma
      fibrinogen. The mean CRP and fibrinogen values in the rhinitis and asthma groups
      were not significantly different when compared to the control group. However, the
      mean SAA levels of both groups were found to be significantly higher than those
      of the control group (p = 0.002 for rhinitis, p = 0.02 for asthma). There was no
      significant correlation between the FEV(1) values and the levels of the serum
      markers. This study demonstrates that acute phase reactant SAA rises in patients
      with allergic rhinitis and patients with asthma. We therefore suggest that SAA
      may have a role in the inflammatory airway disease.

PMID- 15502421
TI  - Clinical and ultrasonographical findings in patients with multiseptate
      gallbladder.
AB  - Multiseptate gallbladder is one of the rare congenital malformations of the
      gallbladder. We present clinical and ultrasonographic findings in seven patients
      with multiseptate gallbladder. One of them had nausea and right upper quadrant
      pain, three had recurrent abdominal pain, while the remaining three patients had
      no symptoms, physical finding and laboratory abnormality which could be
      attributable to the biliary system. In patients with multiseptate gallbladder,
      disturbed motility of the gallbladder may be an etiopathogenetic factor for
      stasis of bile flow and in turn for development of cholelithiasis, cholecystitis
      and right upper quadrant pain.

PMID- 15502422
TI  - Cervical cytologic examination during physical checkup of pregnant women:
      cervical cancer screening in women under the age of thirty.
AB  - Recently, the Ministry of Health, Labor and Welfare proposed that cervical cancer
      screening should be conducted for women aged 20 to 29 years old in Japan.
      However, there are insufficient data available in Japan concerning the screening
      conducted for women under the age of 30. Therefore, we made a survey of the
      results of cervical cytologic examination for pregnant women. 28,616 pregnant
      women were examined as subjects of a study group. A group of 108,289 women,
      subjected to group screening for cervical cancer in Miyagi Prefecture, were
      studied as a control group. The rate of subjects who required close examination
      in the pregnant women's group was significantly higher than that in the mass
      screening group (1.12% vs. 0.84%). The rate of close examination was
      significantly higher in the women 19 years old or younger compared to those in
      the age group of 25 to 39 years old. The rate was also significantly higher in
      women aged 20 to 24 years old than those who are 25 to 34 years old. Of the 321
      subjects who required close examination, 34 cases underwent treatment, and 17
      cases were under age 30. Moreover, all three cases of microinvasive and/or
      invasive carcinoma were under the age of 30 years (23, 23, 27 years old,
      respectively). Our results suggest that screening for cervical cancer in
      pregnancy is a useful means to find cervical neoplasia in young women and is
      effective in reducing the cervical cancer morbidity rate.

PMID- 15502423
TI  - Evaluation of visual function and prognosis for patients with proliferative
      diabetic retinopathy with the low vision evaluator.
AB  - Proliferative diabetic retinopathy (PDR) is a leading cause of visual loss in
      adults in industrialized countries. PDR patients with light perception (LP) or
      hand movement (HM) acuity due to severe vitreous hemorrhage require vitreous
      surgery. The purpose of this study was to determine whether the visual acuity of
      PDR patients with LP or HM can be graded into finer steps with the Low Vision
      Evaluator (LoVE). In addition, we determined whether the LoVE results are
      correlated with the amplitude of the electroretinogram (ERG), the presence of
      retinal detachment (RD), or postoperative visual prognosis. The LoVE instrument
      is a subjective device that measures the thresholds for light stimulus and is
      equipped with a pair of goggles with white light-emitting diodes as the stimulus.
      We measured the LoVE thresholds of 19 PDR patients, whose fundi could not be
      observed due to vitreous hemorrhage and whose visual acuity was LP or HM. The 13
      patients with HM vision had LoVE thresholds that ranged from 25.0 and 40.0 dB,
      and the 6 patients with LP vision had LoVE thresholds that ranged from 20.0 and
      40.0 dB. The LoVE thresholds of 9 patients with RD were significantly lower than
      those of 10 patients without RD (p < 0.001). The LoVE thresholds were correlated
      with the amplitude of the a- and b-waves of the ERG and the postoperative best
      corrected visual acuity (BCVA) (a-wave: r = 0.70, p < 0.001; b-wave: r = 0.71, p
      < 0.001; postoperative BCVA: r = 0.46, p < 0.05). These results indicate that the
      LoVE is capable of grading the visual function of PDR patients with conventional
      LP and HM vision into finer steps. Thus, the LoVE is an invaluable device in
      predicting the postoperative visual acuity of patients with vitreous hemorrhage.

PMID- 15502424
TI  - Effective therapy of a child case of refractory nephrotic syndrome with
      tacrolimus.
AB  - We report here the case of a 9-year-old Japanese boy with nephrotic syndrome
      caused by focal segmental glomerulosclerosis, which was refractory to treatment.
      Although aggressive immunosuppressive therapy consisting of methylprednisolone
      pulse therapy combined with cyclosporine A (CsA) and intermittent low density
      lipoprotein apheresis was effective in overcoming his steroid-resistant state,
      the child became persistently steroid-dependent, that is, more than 0.75 mg/kg
      per day of prednisolone combined with CsA was required to maintain a negative
      test for proteinuria. Since adverse effects of prednisolone, such as short
      stature, obesity, osteoporosis and cataract, were noted, CsA in his treatment
      regimen was replaced with tacrolimus at the dose of 0.1 mg/kg per day, with the
      trough blood level of the drug maintained at around 10 ng/ml. Within 4 months of
      the inclusion of tacrolimus in the treatment regimen, complete remission was
      achieved, with no recurrence of the proteinuria, while the prednisolone dose
      could be tapered to 0.3 mg/kg per day. No adverse effects of tacrolimus were
      observed. These clinical results suggest that tacrolimus may be the drug of
      choice in selected patients with refractory nephrotic syndrome, even if pediatric
      onset cases, at least those in whom the steroid-sparing effects of CsA is
      unsatisfactory.

PMID- 15502425
TI  - Guidelines for writing journal articles in English.

PMID- 15502426
TI  - Urinary incontinence: prevalence and knowledge among community-dwelling Korean
      women aged 55 and over.
AB  - PURPOSE: The prevalence of urinary incontinence (UI) among community-dwelling
      older women in Korea is not well known. This study examined the prevalence of UI
      and UI-related knowledge among community-dwelling Korean women aged 55 and over.
      METHOD: A cross-sectional descriptive-correlational study was conducted. Data
      were collected from 276 women aged 55 and over in a metropolitan city using a
      structured questionnaire. RESULT: Of 276 respondents, 28.3% (n = 78) reported
      experiencing UI. More than 50% of respondents incorrectly agreed with the
      statement that UI is the result of normal aging, with only 20.9% realizing that
      there is an exercise that can control urine leaks when one coughs, sneezes, or
      laughs. Older women who had sought treatment had higher mean score for UI-related
      knowledge. CONCLUSION: This study revealed substantial misconception about UI
      among community dwelling older women, demonstrating that comprehensive
      educational programs need to be developed to increase knowledge of UI.

PMID- 15502427
TI  - Cervical cancer screening in Korean American women: findings from focus group
      interviews.
AB  - PURPOSE: Korean American women have twice the rate of cervical cancer than white
      women and demonstrate low rates in participation in cervical cancer screening.
      This study was to describe the perceptions about cervical cancer and factors
      related to cervical cancer screening among Korean American women. METHOD: Focus
      group methods. RESULT: Five themes emerged. First, knowledge about cervical
      cancer; misconceptions about cervical cancer, its causes, reproductive anatomy
      and the treatment. Second, perceived meanings of having cervical cancer; most of
      the women felt that cervical cancer represented a loss of femininity and
      existential value of womanhood. Third, knowledge about cervical cancer screening
      ; regular medical check-ups were necessary for early detection and prevention of
      cervical cancer. Fourth, experiences and perceived meanings of cervical cancer
      screening; the participants expressed their feelings; embarrassment, fear, shame
      and shyness. Fifth, practices of cervical cancer screening; various intervals in
      participating in cervical cancer screening. But they mentioned several
      deterrents, language, insurance, time constraint, embarrassment, fear of the
      screening results, misbelief about susceptibility, lack of health prevention
      behavior, and lack of information written in Korean. CONCLUSION: Results
      emphasize the critical need for culturally appropriate health education to
      encourage participation of Korean American women in cervical cancer screening.

PMID- 15502428
TI  - Experience of gastric cancer survivors and their spouses in Korea: secondary
      analysis.
AB  - PURPOSE: The purpose of this study was to explore the experiences of gastric
      cancer couples in Korea and to generate a substantive theory integrating the
      experiences of gastric cancer survivors and their spouses as a whole. The
      specific aims of this study were to explore major problems gastric cancer couples
      faced and how they resolved these problems, focusing on inter-relational dynamics
      within the couples and on similarities and differences between the couples.
      METHODS: This was a secondary analysis study using grounded theory techniques.
      The study used the data of 11 married couples which was collected from in-depth
      interviews from two primary studies. The unit of analysis was dyads of gastric
      cancer survivors and their spouses. RESULT: The basic social psychological
      process that emerged from the analysis was "taking charge of their health." Major
      categories involved in this process were identified as 1) adjusting to new diets,
      2) reinforcing physical strength, 3) seeking information, 4) strengthening Ki, 5)
      lowering life-expectations, and 6) going their separate ways. These six
      categories represent major strategies in overcoming critical problems that
      occurred in day-to-day experiences. In terms of the process, the first five
      categories characterize the earlier stage of the process of "taking charge of
      their health," while "going their separate ways" indicates the later stage and
      also the beginning of their separate ways: "pursuing spiritual life" for the
      survivors, and "preparing for the future" for the spouses. CONCLUSIONS: The
      results of this study will help design family care for the people with gastric
      cancer by providing in-depth understanding and insight on the lives of gastric
      cancer couples.

PMID- 15502429
TI  - PTSD symptoms in elementary school children after Typhoon Rusa.
AB  - PURPOSE: A natural disaster negatively affects children's emotional and
      behavioral adjustment. The purpose of this paper was to examine the prevalence,
      symptoms, and correlates of PTSD after the occurrence of Typhoon Rusa. METHOD:
      261 elementary school children living in Kimcheon, which was a devastated rural
      area in South Korea by Typhoon Rusa, were selected. Data were collected 4 months
      after the disaster using the PTSD Reaction Index categories recommended by
      Frederick, severity of PTSD. RESULT: 12.3% of the children had either moderate or
      severe PTSD symptoms; 22.7% reported mild symptoms; and the remaining 65% had sub
      clinical symptoms of PTSD. The most frequent symptom was recurrent fear(67.0%).
      13% to 17.2% of children exhibited difficulty in concentration, sleep
      disturbance, and guilt feeling. The regression model of severity of PTSD was
      composed of the level of exposure to traumatic experiences, grade in school,
      gender, negative coping style, and social support, and explained 34.3% for PTSD
      symptoms. Exposure to traumatic experiences was the strongest factor of all
      predictors. CONCLUSION: Emotional support from friends and coping style were
      correlated with PTSD severity. School-based interventions that emphasizes coping
      with disaster related problems and problem-solving may prove to be useful, and
      may aid in building close and supportive ties with teachers, classmates, and
      friends.

PMID- 15502430
TI  - Effectiveness of a smoking cessation program for adolescents.
AB  - PURPOSE: The purpose of this study was to test the effectiveness of a
      comprehensive smoking cessation program for Korean adolescents. METHOD: The study
      design was quasi-experimental with one pre and three post-tests. The three
      posttests were done immediately after, three months later, and six months after
      the completion of the program. A total of 43 high school students who smoked
      participated in the study with 22 in the experimental group and 21 in the control
      group. The smoking cessation program consisted of 9 sessions with content on
      enhancement of self-efficacy, stress management, correction of distorted
      thoughts, consciousness raising, and assertiveness training. The study variables
      were urine cotinine levels, self-efficacy, stress, and stages of changed
      behavior. RESULTS: Urine cotinine levels significantly decreased in the
      experimental group after the program (F=3.02, p=.06) but significantly increased
      in the control group (F=6.32, p=.004). Self-efficacy and the degree of stress did
      not change in either group. The stages of smoking cessation behavior tended to
      change when compared with raw data for the experimental group. For most
      participants, the stages of change had been precontemplation and contemplation,
      but changed to action and maintenance stage among the experimental group.
      CONCLUSION: The program was effective in smoking cessation and influencing stages
      of change but did not change psychosocial factors such as self-efficacy and
      stress. It is suggested a program should be developed to change psychosocial
      variables on a long-term basis. It is also desirable to involve peers and
      families of adolescents who smoke when planning programs to enhance social
      support.

PMID- 15502431
TI  - [The effect of a child abuse prevention program for parents with disabled
      children].
AB  - PURPOSE: This study describes the ecological variables effect on child abuse
      potential and the results from a prevention program for parents with disabled
      children aiming at decreasing child abuse potential. METHOD: Data was collected
      from 30 parents with disabled preschoolers attending an early education center in
      a community. The program consisted of handouts, small group lectures, support
      group meetings on understanding the disabled child-parents relationship,
      communication skill improvement, non-punitive discipline techniques, and
      influences of child abuse. A non equivalent pre-post test design was employed.
      RESULT: Ecological variables, and parenting self-efficacy, had a significant
      effect on child abuse potential in parents with a disabled child. By regression
      parenting self-efficacy showed (27.1%) child abuse potential. Both parenting self
      efficacy and beliefs in corporal punishment directly related to (52.0%) child
      abuse potential in parents. The program was effective in bringing some positive
      changes on parenting self-efficacy beliefs in corporal punishment, and child
      abuse potential toward disabled children. However, marital discord was not
      significantly effected. CONCLUSION: Child abuse prevention programs should
      decrease the child abuse potential in parents. Thus I recommend a child abuse
      prevention program development; for parents with disabled adolescents, and
      teachers in disabled child education.

PMID- 15502432
TI  - [Meta-analysis of the research findings concerning functional relationships of
      explanatory variables to hope].
AB  - PURPOSE: The purpose of the study was to meta-analyze the relationships of major
      concepts, which were made by synthesizing similar explanatory variables into more
      comprehensive concepts, to hope. METHOD: The relevant researches from Jan 1980 to
      Dec 2003, performed in adults or adult patients, were collected. Using the SAS
      program, meta-analysis were done with the input data of the number of subjects,
      the correlation coefficients provided from most of the studies or a few
      transformed correlation coefficients from F value. In order to get the analysis
      to be done in homogeneous status of the data regarding each relationship of each
      major concept to hope (p>0.05), heterogeneous data were eliminated in repeating Q
      test. RESULT: The major variable regarding relationship to self/transcendental
      being/life (spiritual wellbeing & self esteem) and social support (social support
      & family support) have very large positive effects on hope (D=1.72, D=1.27). The
      negative effect of the variable regarding captive state(uncertainty in illness,
      perceived unhealthiness status, & fatigue) and positive effect of coping
      (approach coping) on hope are in the level between moderate to large (D=-0.61,
      D=0.78). All the effects of the major concepts on hope were verified as
      significant statistically(p=.000). The Fail-Safe numbers showed the significant
      effects of the three major concepts except coping on hope were reliable.
      CONCLUSION: The results can be a guide to advance hope theory for nursing.

PMID- 15502433
TI  - [Effects of taping therapy on the deformed angle of the foot and pain in hallux
      valgus patients].
AB  - PURPOSE: This study was to examine the effects of Taping therapy on the deformed
      angle of the foot and pain in hallux valgus patients. METHOD: The subjects were
      24 feet from 15 patients who were diagnosed withhallus valgus at the orthopedic
      department of K University Hospital in Seoul. Taping therapy was conducted 15
      times overall during a four-week period. Data was analyzed using descriptive
      statistics and t-test. RESULT: The deformed angle of the foot of the hallus
      valgus patients significantly improved from 21.95 (4.38) to 18.75 (4.80) after
      Taping therapy. Pain significantly decreased from 4.73 (1.56) to 3.45 (2.21)
      after Taping therapy. CONCLUSION: The result shows that Taping therapy is
      effective in improving the deformed angle of the foot and in decreasing pain in
      the hallux valgus patients.

PMID- 15502434
TI  - [Validation of Quality of Life Index-Cancer among Korean patients with cancer].
AB  - PURPOSE: The purpose of this study was to validate Quality of Life Index-Cancer
      (Q.L.I.-C) developed by Ferrans (1990) among Korean cancer patients. METHOD: This
      study design was exploratory factor analysis methodology. Q.L.I.-C was translated
      into Korean and reverse-translated into English. The subjects were 357 Korean
      patients with various cancers. Data were collected by questionnaires from May to
      August, 2000 and was analyzed by descriptive statistics, Principal Component
      Analysis for construct validity and Cronbach's alpha coefficient for reliability.
      RESULT: The range of factor loadings was .446 approximately .841. The explained
      variance from the 5 extracted factors was 63.7% of the total variance. The first
      factor 'family' was 35.5%, and 'health & physical functioning', 'psychological',
      'spiritual', and 'economic' factors were 11.5%, 6.9%, 5.6%, and 4.2%
      respectively. Because of cultural difference between Americans and Koreans,
      certain items such as sexuality, job status, and education were deleted from the
      extraction of factors in this study. The Cronbach's alpha coefficient was .9253
      among the 28 items. CONCLUSION: Q.L.I.-C could be applied in measuring quality of
      life of Korean cancer patients. It also recommend to do further studies for
      validation of Q.L.I.-C American and Korean versions relating to cultural
      differences.

PMID- 15502435
TI  - [Perceived stress, ways of coping, and health promoting behavior in patients with
      chronic cardiovascular disease].
AB  - PURPOSE: The purpose of this study was to identify the relationship among
      perceived stress, ways of coping, and health promoting behaviors in patients with
      chronic cardiovascular disease(CCVD). METHOD: Data was collected by
      questionnaires from 436 patients with CCVD in a General Hospital in Seoul. The
      data was analyzed using descriptive statistics, Pearson correlation coefficients,
      and stepwise multiple regression. RESULT: The health promoting behavior showed a
      significant positive correlation with self-efficacy and social support. Also, the
      health promoting behavior showed a significant negative correlation with
      perceived stress and symptoms of stress. The stepwise multiple regression
      analysis revealed that the most powerful predictor of health promoting behaviors
      was symptoms of stress. CONCLUSION: A combination of symptoms of stress, social
      support, self-efficacy, and perceived stress account for 41% of the variance in
      health promoting behaviors of patients with CCVD. Data from this study suggest
      that symptoms of stress, social support, ways of coping, and perceived stress are
      significant influencing factors on health promoting behaviors of patients with
      CCVD.

PMID- 15502436
TI  - [The effects of PBL (Problem-Based Learning) on the metacognition, critical
      thinking, and problem solving process of nursing students].
AB  - PURPOSE: This investigation examined the effect of PBL on the meta-cognition,
      critical thinking, and problem solving process. METHOD: The research design was
      pre-posttest with a nonequivalent control group design. Scenarios for PBL
      sessions were developed on the basis of textbooks and patients' charts and tested
      for content validity. Seventy six nursing students who took a 'Nursing Process'
      course from two nursing schools participated in the experimental group and
      control group. The experimental group performed PBL during the semester. Meta
      cognition and problem solving processes were assessed by questionnaires which
      were developed using pedagogics. Critical thinking was measured by the CCTST
      (California Critical Thinking Skill Test) Form 2000. The data was analyzed by
      repeated measure (pretest-posttest) MANOVA, and correlation analysis. RESULT: PBL
      improved the participants' meta-cognition and problem solving process but not
      critical thinking. The relationship between meta-cognition and the problem
      solving process was supported but the relationship between critical thinking and
      problem solving was not supported. CONCLUSION: These results suggest that PBL has
      a positive effect on nursing students' educational outcomes. To improve the
      problem solving ability of nursing students, PBL should be applied to more
      subjects in the nursing curriculum.

PMID- 15502437
TI  - [The predictors of postpartum depression].
AB  - PURPOSE: This study was designed to determine the predictors of postpartum
      depression. METHOD: One hundred- sixty one women within one year after delivery
      from one public health center located in the northern area of Seoul were used in
      this study. The instruments were a survey of general characteristics, the
      Edinburgh Postnatal Depression Scale, recent life events index, perceived social
      support from family, Quality of marriage index, parenting stress index, and
      Rosenberg's self-esteem inventory. Data was analysed using descriptive
      statistics, Pearson correlation coefficients, and logistic regression. RESULT:
      The average item score of the EPDS was 6.67. 12.4% of respondents, who scored
      above a threshold 12, were likely to be suffering from a depression of varying
      severity. The fitness of the model for explaining postpartum depression from six
      variables, plan for pregnancy, family support, quality of marital relation,
      perceived social support, life events, childcare stress, and self-esteem, was
      statistically significant and the predictive power of these variables was 90.9%.
      The significant predictors of postpartum depression were family support and child
      care stress. CONCLUSION: Further research is needed to identify the prevalence
      rate of postpartum depression using more reliable sampling methods from a large
      general population. Nursing interventions need to be developed for promoting
      family support and reducing childcare stress.

PMID- 15502438
TI  - [Development of a tool in measuring yangsaeng].
AB  - PURPOSE: 'Yangsaeng' is a traditional healthcare regimen for the promotion of
      health and prevention of illnesses by means of specific principles and methods
      for the purpose of living a long and healthy life. The purpose of this paper was
      to develop a tool in measuring Yangsaeng and to verify its reliability and
      validity. METHOD: Content validity was conducted three times by 8 experts. Factor
      analysis was conducted to test its construct validity. RESULT: Thirty-one items
      were selected in 8 factors; Morality Yangsaeng, Mind Yangsaeng, Diet Yangsaeng,
      Activity & rest Yangsaeng, Exercise Yangsaeng, Seasonal Yangsaeng, Sleep
      Yangsaeng and Sex life Yangsaeng. The explanatory variance is 61.76%. Cronbach's
      alpha of the final tool is .89 and that of each factor is .68 approximately .82.
      The analysis of the items shows that the item-total correlation is .40 or higher.
      Criterion-related validity was verified with the CMCHS V1.0 and the KoHSME V1.0.
      CONCLUSION: Since the tool developed in this study was verified in terms of its
      reliability and validity, it could be utilized as a tool for evaluating the
      extent of Yangsaeng.

PMID- 15502439
TI  - [Effects of foot reflexology on essential hypertension patients].
AB  - PURPOSE: This study was to evaluate the effects of foot reflexology on blood
      pressure, serum lipids level and life satisfaction in essential hypertension
      patients. METHOD: The research design used was a nonequivalent control group
      pretest-posttest design. Foot Reflexology was used as the experimental treatment
      from June 23rd, 2003 until August 31st, 2003. Thirty-four subjects were assigned
      to an experimental group(18) and control group(16). Foot Reflexology was
      administered twice a week for 6 weeks and self foot Reflexology was administered
      twice a week for 4 weeks on the experimental group. RESULT: There was a
      significant decrease in systolic blood pressure but no significant decrease in
      diastolic pressure in the experimental group compared to the control group. The
      total cholesterol level in the experimental group compared to the control group
      was not significantly decreased after foot reflexology. However, the triglyceride
      level in the experimental group compared to the control group was significantly
      decreased after foot reflexology. On the other hand, high density lipoprotein and
      low density lipoprotein levels in the experimental group compared to the control
      group was not significantly decreased after foot reflexology. Life satisfaction
      in the experimental group compared to the control group was significantly
      improved after foot reflexology. CONCLUSION: The results proved that foot
      reflexology was an effective nursing intervention to decrease systolic pressure,
      and triglyceride but not for the blood cholesterol and to improve life
      satisfaction. Therefore, blood cholesterol should be further evaluated in a
      larger group of subjects and for a longer period. Further research is regarded as
      necessary to evaluate and to compare effects of self-foot reflexology and foot
      reflexology.

PMID- 15502440
TI  - [Development of college students' condom attitude scale].
AB  - PURPOSE: The aim of this study was to design and evaluate a scale for measuring
      the attitudes toward condom use in sexual relationships. METHOD: A questionnaire
      was administered to 631 college students using a convenience sampling method. The
      psychometric properties (reliability and validity) were evaluated. RESULT: As a
      result of the item analysis, 16 items were selected and the internal consistency
      alpha coefficient was .88. Results indicated that the condom attitude scale is
      composed of three factors: Interruption of sexual pleasure; Protection; and
      Image. The three factors accounted for 59.54% of the variance in the total scale.
      Also, condom attitude was statistically significant (t=7.389, p=.000) between
      consistent condom users and inconsistent users. CONCLUSION: The results
      demonstrate that condom attitudes are multidimensional, and the reliability and
      validity of the scale was supported.

PMID- 15502441
TI  - [Effects of weight-bearing exercise on bone metabolism in college women].
AB  - PURPOSE: This study was done to identify the effects of weight-bearing
      exercise(WBE) on bone metabolism. METHOD: WBE was performed for 12 weeks by
      healthy college women. Bone-related parameters were measured four times during
      this period by evaluating the immunoradiometric assay and enzyme immunoassay.
      Bone mineral densities (BMDs) were measured by dual energy x-ray absorptiometry
      before and after the WBE program. Data was analyzed using t-test, paired t-test,
      x2-test, and repeated measures ANOVA. RESULT: Osteocalcin, a bone formation
      marker, increased more in the experimental group than in the control group based
      on the interaction between time and group (F=3.29 p=.024). Little difference
      between the two groups was found for the other parameters: urinary
      deoxypyridinoline, insulin-like growth factor I, parathormone, serum calcium, and
      serum phosphorus without showing any time interaction between the groups. The
      femoral trochanter BMD rose in the experimental group while that of the control
      group fell, showing a significant difference for BMD (t=3.06 p=.005). However,
      there was no significant difference between the two groups for changes in BMD of
      the forearm, lumbar spine, femoral neck, and femoral ward's triangle. CONCLUSION:
      These findings supported the WBE is beneficial for increasing bone formation in
      college women and long-term application is needed to substantiate the effects of
      WBE as a intervention in promotion of bone-health.

PMID- 15502442
TI  - [Grounded theory approach to health care of older adults at a doctorless farm
      village].
AB  - PURPOSE: The purpose of this study was to explore how older adults kept their
      health good at a doctorless farm village. METHOD: Data was collected through in
      depth interviews with 32 participants who were over 65 years old and analyzed in
      terms of Strauss and Corbin's (1990) grounded theory methodology. RESULT: The
      Core Category of health care of older adults was identified as "enduring physical
      changes by themselves". The process of this could be divided into 4 stages : the
      stage of bearing, the stage of managing daily living activities, the stage of
      passively collecting information and the stage of minimally utilizing health care
      services. Older adults accepted the aging process positively but health sources
      limitation passively, so they managed daily living activities and used natural
      food for health. In addition, they collected information related to health care
      and used health care services minimally. CONCLUSION: We found that participants
      managed their health passively because of negative attitudes toward active health
      behaviors of older adults by themselves and the difficulty of access to health
      care services. Therefore, various community health services for older adults need
      to be developed to empower older adults in the community.

PMID- 15502443
TI  - [Model development of an elderly health promotion center: the effect of a social
      support program at a community health center].
AB  - PURPOSE: The purpose of this study was to develop a model of an elderly health
      promotion center after witnessing the effect of a social support program on
      dependent variables in older adults at a local community health center. METHOD:
      The subjects were 60 female adults over 65 years dwelling in a rural area, and
      they were divided into experimental and control groups each with 30 people. A
      social support program was implemented 6 hours a day, 3 times a week, for 4
      months in the experimental group. Included was health assessment, health
      education, counseling, consultation, exercise, physical & occupational therapy,
      primary care, recreation, lunch & transfer service. Data was collected from May
      1st to September 14th, 2002 by questionnaires, and analyzed by x2-test, t-test,
      Pearson's correlation coefficient and stepwise multiple regression using SAS.
      RESULT: The social support program in the elderly was very effective on all
      dependent variables of physical health (t= 4.68, p= .001), health knowledge (t=
      3.60, p= .001), life satisfaction (t= 8.65, p= .001), and health promoting
      behaviors (t= 5.23, p= .001). CONCLUSION: The Social Support Program at a
      Community Health Center was effective on health promoting behaviors in the
      elderly.

PMID- 15502444
TI  - [Breast cancer screening and repeat screening].
AB  - PURPOSE: This study was to investigate the characteristics and related factors of
      breast cancer screening and repeat screening, and to propose nursing
      interventions to increase the rate of breast cancer screening and repeat
      screening. METHOD: Study subjects was 236 women residing in the community,
      teachers and nurses who were older than 45 were recruited. Data was collected
      with self administered questionnaires from July 1st to August 31st, 2003 and
      analysed using SPSS/WIN 10.0 with X(2)test, t-test, and stepwise multiple
      logistic regression at a significant level of =.05. RESULT: The breast cancer
      screening rate was 57.2%, and repeat screening rate was 15.3%. With the multiple
      logistic regression analysis, factors associated with mammography screening were
      age and perceived barriers of action, and factors related to the repeat
      mammography screening were education level and other cancer screening experience.
      CONCLUSION: Based on the results, we recommend the development of an intervention
      program to decrease the perceived barrier of action, to regard mammography as an
      essential test in regular check-up, and to give active advertisement and
      education to the public to improve the rates of breast cancer screening and
      repeat screening.

PMID- 15502445
TI  - [The effect of self-foot reflexology on the relief of premenstrual syndrome and
      dysmenorrhea in high school girls].
AB  - PURPOSE: This study was aimed to identify the effect of self-foot reflexology on
      the relief of premenstrual syndrome and dysmenorrhea in high school girls.
      METHOD: Study subjects was 236 women residing in the community, teachers and
      nurses who were older than 45 were recruited. Data was collected with self
      administered questionnaires from July 1st to August 31st, 2003 and analysed using
      SPSS/WIN 10.0 with Xtest, t-test, and stepwise multiple logistic regression at a
      significant level of =.05. RESULT: The breast cancer screening rate was 57.2%,
      and repeat screening rate was 15.3%. With the multiple logistic regression
      analysis, factors associated with mammography screening were age and perceived
      barriers of action, and factors related to the repeat mammography screening were
      education level and other cancer screening experience. CONCLUSION: Based on the
      results, we recommend the development of an intervention program to decrease the
      perceived barrier of action, to regard mammography as an essential test in
      regular check-up, and to give active advertisement and education to the public to
      improve the rates of breast cancer screening and repeat screening.

PMID- 15502446
TI  - [Effects of a comprehensive rehabilitation program for mastectomy patients].
AB  - PURPOSE: The purpose of this study was to investigate the effect of a
      comprehensive rehabilitation program on physical function, immune response,
      fatigue and quality of life in mastectomy patients. METHOD: The subjects included
      fifty-five patients with breast cancer (27 in the control group and 28 in the
      experimental group). The subjects in the experimental group participated in a
      comprehensive rehabilitation program for 10 weeks, which was composed of 1
      session of education, 2 sessions of stress management, 2 sessions of exercise,
      and 1 session of peer support group activity per week. RESULT: The results
      revealed an increase in shoulder extension, abduction, external rotation, and
      internal rotation of the affected upper extremity, and in shoulder extension and
      abduction of the healthy upper extremity. Also an increase in quality of life and
      a decrease in fatigue were significantly higher in the experimental group than
      the control group. However, the results revealed that the natural killer cell
      ratio of the experimental group increased but there was no significant difference
      from that of the control group. CONCLUSION: The 10-week comprehensive
      rehabilitation program showed a large affirmative effect on physical function,
      fatigue and quality of life of breast cancer patients after a mastectomy.

PMID- 15502447
TI  - [Effects of sensory stimulation program conducted by primipara on the physical
      growth and mother-infant feeding interaction for full term infant].
AB  - PURPOSE: The purpose of this study was to identify the effectiveness of sensory
      stimulation program administered by primipara on the physical growth and mother
      infant feeding interaction for the first 6 months of infancy. METHOD: Data were
      collected from December 1, 2001 to June 30, 2003. A total of 35 mothers and their
      infants were assigned to a control (n=17) and an experimental (n=18) group.
      Mothers in the experimental group received education related to sensory
      stimulation program and administered to their infants twice a day for 6 months.
      Both groups were measured the weight, length, head circumference and chest
      circumference of infants at 6 weeks, 10 weeks, 14 weeks, 18 weeks, and 22 weeks
      and the mother-infant feeding interaction at 6 weeks, 10 weeks through the home
      visiting. RESULT: Compared to the control group, the experimental group had
      significantly larger increases in head circumference for intervention period. In
      addition to, the experimental group showed significantly higher score in mother
      infant interaction than control group. CONCLUSION: These data suggested that
      sensory stimulation program administered by primipara may improve the physical
      growth of full term infant and mother-infant feeding interaction.

PMID- 15502448
TI  - [The effects of tai chi exercise program on blood pressure, total cholesterol and
      cortisol level in patients with essential hypertension].
AB  - PURPOSE: The purpose of this study was to determine the effects of a 6-week Tai
      Chi exercise program on reducing blood pressure for hypertensive patients.
      METHOD: A non-equivalent pretest-posttest experimental design was used.
      Participants were recruited from the Community Health Center in Busan, Korea.
      Twenty-eight hypertensive patients participated in this study. Among them,
      fourteen were in the experimental group and the rest are in the control group.
      Members in the experimental group participated in a 6- week program of Tai Chi
      exercise. In order to evaluate the effects of the Tai Chi program, blood
      pressure, total cholesterol, and cortisol level were measured before and after
      week 6. RESULT: After the 6-week Tai Chi program, there were significant
      differences in systolic pressure (t=-3.13, p= .004) and diastolic blood pressure
      (t=-4.75, p= .000) in the experimental group when compared to the control group.
      However there were no significant differences in the total cholesterol (t=1.07,
      p=.294) and cortisol level (F=1.35, p= .256). CONCLUSION: These results suggest
      that a 6-week Tai Chi program can be utilized as an effective nursing program to
      reduce blood pressure for hypertensive patients.

PMID- 15502449
TI  - [Nurses' research activities and barriers of research utilization].
AB  - PURPOSE: This study was to describe nurses' research activities, perceptions and
      performances of evidence-based practice and barriers to the use of research
      evidence in nursing practice in Korea. METHOD: A cross-sectional survey design
      was used. A questionnaire, except for Barriers Scale, was developed for the
      study. Data was collected from a convenient sample of 437 registered nurses
      working at research and education oriented university hospitals. RESULT: Nurses'
      research-related activities were relatively low compared to previous studies.
      Also perceptions and performances of evidence based nursing practice were low.
      Preferred informational resources for clinical decision making were identified as
      ward manuals/clinical guidelines, manager/senior nurses, and literature/research.
      The major barriers to research utilization were a lack of implication for
      practice along with inadequate facilitation to implement research evidence and
      difficulty understanding research written in English. Priorities of barriers
      factor were Administrator, Communication, Adopter, and Research. CONCLUSION: The
      findings provide directions for future training, education, and managerial policy
      to achieve successful evidence based nursing practice.

PMID- 15502450
TI  - [Development of a scale to measure Korean smoking temptation].
AB  - PURPOSE: Smoking temptation is the central concept related to relapse within the
      context of smoking. Therefore for effective smoking cessation interventions, a
      scale to measure smoking temptation is necessary. This study was carried out to
      develop scale to measure smoking temptation. METHOD: This study utilized
      Cronbach's alpha, spilt-half coefficient and test-retest correlation in analyzing
      the reliability of the collected data and expert group, factor analysis, item
      analysis multitrait-multimethod method and known-group technique to analyze
      validity. RESULT: Twenty-five items were selected from a total of 33 items. The
      Cronbach's alpha coefficient for internal consistency was .93, spilt-half
      coefficient .91, and 2 week interval test-retest correlation .93 for the 25 items
      on the smoking temptation scale. Five factors evolved by factor analysis, which
      explained 57.28 % of the total variance. The smoking temptation scale was
      effective in differentiating the subjects at each stage of change for smoking
      cessation and there were significant negative correlations between smoking
      temptation and self efficacy for smoking cessation and significant positive
      correlations between smoking temptation and the Fagerstrom Tolerance
      Questionnaire. CONCLUSION: The scale for measuring smoking temptation in Korean
      in this study was evaluated as a tool with a high degree of reliability and
      validity.

PMID- 15502451
TI  - [Content analysis of the experience of preceptors in clinical education for
      senior student nurses].
AB  - PURPOSE: The purpose of this study was to identify experiences of nurses who
      served as preceptors in clinical education for senior student nurses in a college
      of medicine in Wonju city. METHOD: Data was collected from 20 preceptors
      instructing senior student nurses in 2001 using a self-completion questionnaire.
      To analyze data, content analysis was done using an analysis scheme developed by
      the investigators. RESULT: The analysis scheme consisted of 7 categories and 25
      subcategories. 135 significant statements were analyzed and categorized.
      Preceptors indicated that they were role models, socialization facilitators and
      educators while instructing students in the clinical practicum. In performing the
      preceptors' role, preceptors reported that their most important change was self
      enhancement,and positive experience was a constructive work atmosphere. The most
      important factor facilitating the preceptors' role performance was support from
      head nurses, and the most discouraging factor was work loads. CONCLUSION: This
      study suggests that interventions for encouragement and socialization of
      preceptors should be developed to promote clinical education for senior student
      nurses.

PMID- 15502452
TI  - [A study on health concern, self-rated health, health status, and health
      promotion behavior of elderly women in urban area].
AB  - PURPOSE: This study was conducted to examine the relationship among health
      concern, self-rated health, health status, and health promotion behavior of
      elderly women in urban areas. METHOD: The subjects of this study consisted of 271
      Korean elderly women over 65 years. The data was collected through personal
      interviews using questionnaires from March to May of 2003. The data was analyzed
      by the SPSS (ver.10.0) computer program, and it included descriptive statistics,
      t-test, one way ANOVA, and the pearson correlation coefficient. RESULT: There was
      a significant positive correlation between self-rated health and health status.
      Health promotion behavior related to all health concerns, self-rated health, and
      health status. CONCLUSION: This study showed that strategies of elderly care
      intervention to put in practice health promoting behavior is needed to improve
      quality of life in elderly women. In addition, health education appropriate for
      health maintenance and health promotion must be done for daily living to maintain
      well-being for the rest of their lives.

PMID- 15502453
TI  - [Women caregivers' experiences in caring at home for a family member with
      dementia: a feminist approach].
AB  - PURPOSE: The purpose of this study was to explore women caregivers' lived
      experiences in caring at home for a family member with dementia and to identify
      conditions that oppress women in the context of family caregiving. METHOD: This
      study was conducted within the feminist perspectives using qualitative secondary
      data. Ten secondary data conveying self reflective contents were selected from
      the 25 original data obtained in 1999 to 2000. RESULT: Six themes that emerged
      from the qualitative thematic content analysis were; androcentric view of family
      caregiving, undervalued family caregiving by the family members, Self
      rationalization in the context of family caregiving, family-centric care
      mechanism, exemplary caring within the family context, and inter-familial
      relationships among women. CONCLUSION: The main focus of feminist research is to
      provide empowerment for the women research participants and to bring about social
      change of oppressive constraint through some actions. On the basis of the
      research findings, therefore, action strategies from feminist perspectives were
      suggested in some aspects of health care delivery sectors, nursing education and
      research sectors, and administrative sectors.

PMID- 15502454
TI  - Local complications after cosmetic breast implant surgery in Finland.
AB  - Concerns regarding potential health effects of silicone breast implants have
      recently shifted from long-term illnesses to postoperative local complications.
      In this study, occurrence of local complications and treatment procedures were
      evaluated in a population of 685 Finnish women who received cosmetic silicone
      breast implants between 1968 and 2002. Patient records were abstracted, and
      additional information was gathered using a structured questionnaire that was
      mailed to 470 of the women in the cohort. Overall, 36% of the women had 1 or more
      diagnoses of postoperative complications in their medical records. The most
      common complication was capsular contracture, occurring in 17.7% of women and
      15.4% of implantations. Other complications were more rare. The majority of women
      (74%) needed no postoperative treatment. However, 22% of women required 1 or more
      surgical procedures after the primary implantation. Most of the women were
      satisfied with the implantation, but only 40% considered the preoperative
      information on possible risks related to implantation as sufficient. With respect
      to the occurrence of local complications following cosmetic breast implantation,
      the findings of this study are consistent with previous studies. Frequencies of
      complications were remarkably similar in medical records and self-reports.

PMID- 15502455
TI  - Retrospective case review of capsular contracture after two-stage breast
      reconstruction: is colonization of the tissue expander pocket associated with
      subsequent implant capsular contracture?
AB  - Periprosthetic capsular contracture is a common problem associated with implant
      based breast reconstruction. The purpose of this study was to determine if
      bacterial colonization of the tissue expander contributes to contracture of the
      permanent implant. Medical records were reviewed for 86 patients (124 tissue
      expanders) between 1997 and 2001 in 1 institution. Three specimens taken from the
      expander were cultured. The overall incidence of colonization was 42.7%; 49.4%
      (38.8-60.0) of immediate and 28.2% (14.1-42.3) of delayed expanders had at least
      1 positive culture site (P = 0.043). The most common organisms were
      Propionibacterium acnes (57.6%), Staphylococcus epidermidis (31.0%), and
      Peptostreptococcus (5.8%). Statistical analysis revealed no significant
      difference between colonization of the expander and capsular contracture of the
      permanent prosthesis (P = 0.59). 45.8% (25.9-65.8) of breasts irradiated
      preoperatively developed contracture versus 14% (7.2-20.8) with no irradiation (P
      = 0.0013). These results suggest that colonization of the expander occurs
      frequently, irradiation predisposes to contracture, and colonization did not
      contribute to secondary implant contracture in this study population.

PMID- 15502456
TI  - The effect of intravenous dopamine and dobutamine on blood circulation during a
      microvascular TRAM flap operation.
AB  - A study was conducted to assess the effect of intraoperatively administered
      inotropic agents on blood flow in the recipient and donor vessels, during breast
      reconstruction with a muscle sparing free TRAM flap. Twenty-one consecutive
      patients were randomized into 3 groups receiving either dopamine, dobutamine, or
      placebo. When the flap and all vessels had been fully dissected but not yet
      divided, the study drug was administered intravenously for 15 minutes.
      Hemodynamic parameters and transit-time flow of the thoracodorsal and inferior
      epigastric arteries were monitored. Both dobutamine and dopamine infusions
      resulted in significant raises in cardiac output and mean arterial pressure.
      However, while dobutamine resulted in a higher cardiac output (P = 0.001) and a
      decrease in systemic vascular resistance (P = 0.028), the increase in mean
      arterial pressure was greater with dopamine (P = 0.002). Only the dobutamine
      group showed increased blood flow, in both the thoracodorsal (P = 0.043) and the
      inferior epigastric (P = 0.043) arteries. If vasoactive agents are needed during
      microvascular anesthesia, dobutamine seems to be more advantageous than dopamine.

PMID- 15502457
TI  - The impact of Pfannenstiel scars on TRAM flap complications.
AB  - For the past two decades, the transverse rectus abdominis musculocutaneous (TRAM)
      flap has been a mainstay of postmastectomy breast reconstruction. Because the
      flap depends on musculocutaneous perforating vessels from the rectus muscle for
      survival, some authors have raised concerns about increased risks of TRAM flap
      loss in patients with scars from previous abdominal surgeries, particularly those
      with Pfannenstiel scars. To assess the effects of Pfannenstiel scars on
      complication rates, we retrospectively evaluated the inpatient and outpatient
      records of 241 patients undergoing TRAM reconstruction in a single institution
      over an 11-year period. Of these patients, 51 had previous Pfannenstiel scars.
      while 190 did not. Controlling for potential confounding variables (body mass
      index and timing of reconstruction), logistic regressions found no significant
      differences between the Pfannenstiel and nonPfannenstiel cohorts in the rate of
      flap loss (15.7% and 20%, respectively; P = 0.376) or in the incidence of
      postoperative abdominal donor site laxity (17.6% and 12.1%, respectively; P=
      0.361). Within the Pfannenstiel group, the type of TRAM reconstruction (ie,
      pedicle versus free flaps) did not have a significant effect on complication
      rates. We conclude that previous concerns over the impact of preexisting
      Pfannenstiel scars on TRAM flap complications are unfounded.

PMID- 15502458
TI  - A new wound closure achieving and maintaining device using serial tightening of
      loop suture and its clinical applications in 15 consecutive patients for up to
      102 days.
AB  - A device that can both achieve and maintain wound closure by serial tightening of
      a loop suture was developed. The device consists of 3 components: a hollow
      plastic cylinder with a 1-way locking mechanism, a flat plastic strip passing
      though the cylinder, and a plastic cushion between the cylinder and the skin. The
      body of the device is composed of a soft cylinder and a hard strip. This
      difference in flexibility enables the device to absorb impacts of positional
      changes and daily activities, while the device preserves tension of loop suture
      and wound closure ().(Figure is included in full-text article.)After debridement
      or excision of a lesion, the passage of 0-1 nylon suture is designed. The nylon
      suture is threaded through the deep dermis across the wound. Both ends of the
      suture are then tied to make a loop, which is secured to 2 holes at one end of a
      plastic strip. The plastic strip, which holds the loop suture, is pulled away
      from the skin gradually through a hollow plastic cylinder to approximate wound
      margins ().(Figure is included in full-text article.)From January 2003 to August
      2003, the device was applied 21 times in 15 consecutive patients. A mean
      stretching of 42.0 mm was performed for defects with a mean shortest dimension of
      24.5 mm (from 2 mm to 60 mm). All 21 wounds were closed primarily (21/21 = 100%),
      and the closure was maintained successfully for 18 wounds (18/21 = 85.7%) in 13
      patients (13/15 = 86.7%). The device was left in situ for as long as 102 days
      (average application time of 34.5 days). Three wound dehiscences (3/21 = 14.3%)
      occurred in 2 diabetic foot patients, which were cured by skin grafting. In 2
      sacral pressure ulcer patients, minimal skin lacerations were caused by the loop
      sutures at the skin entrance site but without true wound dehiscence. These
      lacerations healed with minimal debridement and routine wound dressing within 2
      weeks. This instrument was devised to overcome the limitations of previous skin
      stretching methods. It has wider indications and shows better compliances. In
      particular, because of its longer period of application, the device does not only
      stretch the skin to achieve wound closure, but also helps maintain it during
      wound healing.

PMID- 15502459
TI  - Combined free fibular osteocutaneous-lateral calcaneal fasciocutaneous flap for
      reconstruction of composite oromandibular defects.
AB  - The free fibular osteocutaneous flap is often used in the reconstruction of
      composite oromandibular defects. In contrast, the lateral calcaneal flap has
      never been used in oromandibular reconstruction. On the basis of their anatomic
      continuity, the authors combined the free fibular osteocutaneous flap with the
      lateral calcaneal skin paddle to obtain 2 adjoining flaps in different anatomic
      areas with the same vascular axis. The authors report their experience in 3
      patients with composite oromandibular defects. In 1 patient without an outer skin
      defect, only a sensory lateral calcaneal skin paddle with a fibular osseus flap
      was harvested. The lateral calcaneal flap carried the sural nerve as a sensory
      flap in 2 patients, and the result was passable. Only 1 patient encountered
      superficial flap tip necrosis at the lateral calcaneal skin paddle, and recovered
      well after wound care. In conclusion, a flap with many specific features is a
      feasible choice for reconstruction of composite oromandibular defects.

PMID- 15502460
TI  - Sensate first dorsal metacarpal artery flap for resurfacing extensive pulp
      defects of the thumb.
AB  - Finding an appropriate soft-tissue grafting material to close a wound located
      over the distal phalanx of the thumb, especially the pulp region, can be a
      difficult task. A sensate first dorsal metacarpal artery flap, mobilized from the
      dorsum of the adjacent index finger and used as an island pedicle skin flap, can
      be useful for this purpose. The pedicle includes the ulnar branch of the first
      dorsal metacarpal artery, the dorsal veins, and the cutaneous branch of the
      radial nerve. Although this tiny artery is anatomically variable, safe dissection
      can be achieved by including the radial shaft periosteum of the secondary
      metacarpal bone and the ulnar head fascia of the first interosseous muscle. This
      approach has been used for 8 individuals with extensive pulp defects of the thumb
      over the past 3 years. Skin defects in all patients were combined with bone,
      joint, or tendon exposure. All flaps survived completely. This 1-stage procedure
      is reliable and technically simple. It provides sensate coverage to the pulp of
      the thumb but also avoids nerve repair or more complicated microsurgery.

PMID- 15502461
TI  - The use of free anterolateral thigh flap for reconstructing soft tissue defects
      of the lower extremities.
AB  - The goal of soft tissue reconstruction in the lower extremities is to provide a
      functional and cosmetically acceptable limb. The anterolateral thigh flap has
      become one of the most popular options for soft tissue defect reconstruction
      recently because of the large amount of skin available and the reliable and
      versatile nature of this material. The purpose of this article is to present our
      experiences with the free anterolateral thigh flap for the reconstruction of soft
      tissue defects of the lower extremity. From April 2002 to October 2003, 31
      consecutive free anterolateral thigh flaps were used. There were 24 male and 7
      female patients, and their ages were between 3 and 78 years. The size of the
      flaps ranged from 11 to 34 cm long and 6 to 16 cm wide. In 9 patients, the flaps
      were harvested in a flow-through manner to both reconstruct soft tissue defects
      and protect and maintain the vascular status of the lower extremities. In these
      patients, the pedicle was interposed between vascular gaps, either present or
      created, in the extremity. The patency of distal anastomosis with the course of
      the distal vessel was confirmed by using conventional Doppler flow monitoring in
      flow-through flaps. In 4 cases, thinning of the flap was performed. In 3
      patients, flaps were used in a neurosensorial fashion. Four flaps required
      reoperation due to vascular compromises. While 3 of these were salvaged, 1 flap
      was lost due to recipient arterial problems. Sixteen cases underwent split
      thickness skin grafting of the donor site. No infection or hematomas were
      observed. We conclude that the anterolateral thigh flap is an ideal and versatile
      material, especially for lower extremity reconstructions, with its functional and
      cosmetic advantages, and it can be considered a suitable alternative to the most
      commonly used conventional soft tissue flaps.

PMID- 15502462
TI  - Plantar burns in children: epidemiology and sequelae.
AB  - Pediatric plantar burns present with significant and unique characteristics. The
      treatment of choice remains controversial, and any alteration of the anatomy will
      lead to alteration in gait. To study the outcome of conservative treatment of
      plantar burns and determine risk factors, 40 pediatric patients affected with
      isolated plantar burns were studied. All burns were treated with silver
      sulfadiazine and early ambulation, and those that did not heal within 3 weeks
      were autografted. Twenty-eight patients (70%) had partial-thickness burns and 12
      patients (30%) full-thickness burns. Complications during the acute period
      included 1 episode of cellulitis and 1 patient with prolonged difficulties with
      ambulation. Three patients required excision and autografting, and none of them
      developed late sequelae. Five patients presented with late sequelae, and all had
      in common complete healing with conservative treatment, young age, and a longer
      healing time (24.4 days). We conclude that conservative treatment of pediatric
      plantar burns has a negligible complication rate. Burns that do not heal within 3
      weeks are best managed with excision and autografting, which had a 0% incidence
      of complication rate in this series.

PMID- 15502463
TI  - Double pennant technique: elongating the helix using rim flaps to correct the
      constricted ear.
AB  - In a Tanzer group 2B or group 3 constricted ear, the short helix must be
      elongated with additional tissues. To do this, we have developed a new method of
      surgical repair using 2 pennant-shaped rim flaps. Six constricted ear patients
      underwent correctional ear plasty using this method. Four of the deformities were
      Tanzer group 2b and 2 were group 3. Our surgical procedure elongated the
      patients' helix from 7 to 22 mm, leaving them with smooth curvature and a good
      color match to the adjoining skin.

PMID- 15502464
TI  - Tuberculosis of the metacarpals and phalanges of the hand.
AB  - Skeletal tuberculosis (TB) is less common than the pulmonary form. Involvements
      of the metacarpals and phalanges of the hand are infrequent. The authors report
      their experience with treatment and outcome of TB of the metacarpals and
      phalanges of the hand in 7 patients. There were 4 women and 3 men in the study
      who ranged in age from 3 to 60 years (average age, 22.7 years). The duration of
      complaints at presentation ranged from 4 to 17 months (average, 9 months). The
      most common presentation was pain and swelling. The presumptive preoperative
      diagnoses were bone tumor in 4 patients, spina ventosa in 2, and chronic pyogenic
      osteomyelitis in 1 patients. The results of the laboratory examination showed a
      mild increase in the erythrocyte sedimentation rate. No patient had an active
      tubercular lesion or history of pulmonary disease. The diagnosis was based on the
      clinical picture and radiographic features, and was confirmed by open biopsy. No
      patient had bony debridement or arthrodesis to control the infection. The
      treatment of all patients began with a 4-drug regimen for 2 months, followed by a
      2-drug regimen for 10 months. The mean follow-up was 30.28 months (range, 16-52
      months). At the time of the last follow-up, all lesions had healed with no
      recurrence. The functional results were satisfactory in all patients. One patient
      with thumb metacarpophalangeal TB had joint irregularity and thumb metacarpal
      shortening. Arthrodesis was not needed in any patient. TB of the metacarpals and
      phalanges of the hand can be difficult to diagnose during the early stages. TB
      should be suspected in cases of long-standing pain and swelling in the
      metacarpals and phalanges. It is necessary to keep TB in mind when making the
      differential diagnosis of several osseous pathologies.

PMID- 15502465
TI  - Comparison of accuracy of three-dimensional spiral computed tomography, standard
      radiography, and direct measurements in evaluating facial fracture healing in a
      rat model.
AB  - Complex maxillofacial fractures demand a detailed understanding of the three
      dimensional (3D) pattern of injury. Evaluation of the outcome of the facial
      fracture repair additionally requires optimal demonstration of fracture gap, bony
      union, fibrous callus or incorporation of fracture ends, presence of incomplete
      fusion, or pseudoarthrosis. Although 3D computed tomography (CT) is reliably used
      for the diagnosis of complex facial fractures, its value in facial fracture
      healing is unknown. An experimental study was conducted to determine the accuracy
      of 3D spiral CT scans in evaluating facial fracture healing during the early and
      late postoperative periods. In 10 adult Wistar Albino rats, a standardized bone
      defect (3 mm) was created within the mid portion of each zygomatic arch (n = 20).
      At 10 and 20 weeks postfracture, gap distance displayed by 3D CT and plane
      radiography (posteroanterior) were measured. At 20 weeks postfracture,
      intraoperative measurement was also performed. A comparison between 3D CT,
      radiography, and intraoperative findings was performed. At 10 weeks postfracture,
      the fracture sites displayed larger bone defects in imaging with 3D CT than with
      plane radiography. The difference between groups was statistically significant (P
      < 0.05). The mean defect size imaged by 3D CT was 0.91 +/- 0.82 mm (standard
      deviation) and by plane radiography was 0.42 +/- 0.16 mm. At 20 weeks
      postfracture, the mean defect size imaged by 3D CT was 0.56 +/- 0.64 mm, and by
      plane radiography was 0.38 +/- 0.22 mm. The difference between groups was not
      statistically significant (P > 0.05). The defect size imaged by both plane
      radiography and 3D CT was significantly less than the measurement obtained from
      the intraoperative assessment (P < 0.05). It was concluded that 3D CT has limited
      benefit in the detection of newly formed bone at week 10 and in the detection of
      fibrous callus, which can eventually give rise to the bony tissue. Plane
      radiography is more valid during the early postoperative period (week 10),
      because it can detect the fibrous callus and newly formed bone more precisely.
      Gap distance between fracture ends could be determined by 3D CT accurately at
      week 20, although there was a tendency, which was not statistically significant,
      to overestimate the amount of bone defect measured by 3D CT when compared with
      that of plane radiography.

PMID- 15502466
TI  - Delay in neurovenous flaps: experimental and clinical experience.
AB  - The objective of this study was to examine the effects of the standard surgical
      delay in the flaps based on the cutaneous branches of the vascular axis around a
      superficial sensory nerve. The delay procedure was experimentally tested in rats
      and subsequently used in patients. In the experimental study, the survival of a
      delayed inferior epigastric neurovenous flap was compared with that of a
      nondelayed inferior epigastric neurovenous flap. One type of clinically
      applicable delay pattern (standard bipedicled technique) was employed. A 3 x 3 cm
      flap was raised in 20 female Wistar rats assigned randomly to 2 groups. Each
      group consisted of 20 flaps. The standard bipedicled delay pattern increased the
      percentage survival of the delayed inferior epigastric neurovenous flap. The
      survival percentage of the delayed flaps was 59.8 +/- 185.0 (P < 0.5). The
      histologic findings of the skin revealed that our delay procedure enhanced the
      perfusion of the flap by dilating the arterial network. Stimulated by our
      experimental findings, we used the island bipedicled surgical flap delay or
      combined strategic-standard delay in the distally pedicled sural flap
      successfully on 9 cases.

PMID- 15502467
TI  - Dual synergistic effect: the effect of dexamethasone plus carnitine on skin flap
      survival.
AB  - Dexamethasone has well-known useful effects in dealing with the progression of
      necrosis. Carnitine is an endogenous cofactor, for having a regulatory action on
      the energy flow from different oxidative sources. The aim of this study was to
      determine whether combined local dexamethasone and systemic carnitine
      administration would result in an additive enhancement of skin flap survival in
      the rat model. A rectangular (3 cm x 11 cm) dorsal random skin flap was elevated
      on the rats and then sutured back into its original site with separate sutures.
      Overall, 40 rats were allocated randomly into 4 groups: Group 1 (control group, n
      = 10), group 2 (Dexamethasone group, n = 10, 2.5 mg/kg), group 3 (carnitine
      group, n = 10, 100 mg/kg), group 4 (dexamethasone plus carnitine group, n =
      10).The mean flap survival area was 57.50 +/- 5.2% (mean survival area +/- SD) in
      control group (group 1), 71.5 +/- 4.8% in the dexamethasone group (group 2), 73.0
      +/- 5.5% in the carnitine group (group 3), 85.30 +/- 6.1% in the dexamethasone
      plus carnitine group (group 4). In conclusion, based on the findings of this
      experimental study, the synergistic effect of carnitine and dexamethasone on skin
      flap viability is determined.

PMID- 15502468
TI  - An unusual complication of septorhinoplasty: massive subarachnoid hemorrhage.
AB  - Septorhinoplasty is a very common operation in the practice of plastic surgery
      and otolaryngology. We report a case with massive subarachnoid hemorrhage
      originating from carotid artery injury, following corrective septorhinoplasty.
      The carotid rupture is a very rare but life-threatening, major complication of
      nasal surgery. Therefore, surgeons performing surgery in this area should be very
      careful and aware of this entity. According to our knowledge, this is the fourth
      case report of a carotid artery injury following septorhinoplasty, but it is the
      first bilateral and lethal one in the literature.

PMID- 15502469
TI  - End-to-side nerve graft for facial nerve reconstruction.
AB  - Reconstruction of multiple branches of the facial nerve by sural nerve graft
      using end-to-side nerve suture was performed successfully on a patient with
      advanced parotid tumor. In this technique, one end of the grafted nerve is
      sutured with the stump of the facial nerve trunk in an end-to-end manner.
      Epineural windows are made on the nerve graft, and the distal stumps of the
      facial nerve branches (temporal, zygomatic, and buccal branches) are sutured with
      the graft in an end-to-side manner. Functional recovery of all branches and
      satisfactory facial expression were obtained within 2 years postoperatively.
      Axonal regeneration through the graft was confirmed by electrodiagnosis.
      Regeneration through the anastomosis at the stump of the facial nerve trunk using
      this technique is more efficient than conventional cable grafting, and the length
      of the nerve required is minimal. This technique may be a useful option for
      facial nerve reconstruction managing multiple branches.

PMID- 15502470
TI  - The medial sural(MEDIAL GASTROCNEMIUS) perforator local flap.
AB  - The medial sural(MEDIAL GASTROCNEMIUS) perforator flap has previously been
      described as a free flap distinguished by the potential for a large yet thin
      cutaneous flap that incorporates the calf skin territory. Its medial sural
      vascular pedicle can be tailored to allow reach extending from the popliteal
      fossa to the suprapatellar area also as a local flap without any need for
      microsurgery. Two variations presented are possible as either a broad-based
      peninsular or island flap. Both are alternatives to the more traditional medial
      gastrocnemius muscle flap and, because this is a true muscle perforator flap,
      function is always preserved.

PMID- 15502471
TI  - Free adipofascial flap interposition for pediatric posttraumatic forearm
      synostosis with closed head injury.
AB  - A case report is presented of a 12-year-old male after a motor vehicle accident:
      head injury and multiple fractures, including bilateral both bone forearm
      fractures. The patient developed bilateral extensive forearm synostosis that
      required release and interpositional free flap at 6 months postinjury. At 3-year
      follow-up, the patient has maintained full forearm rotation and reports
      unrestricted sports and other recreational activities.

PMID- 15502472
TI  - Treatment of nevoid hyperkeratosis of the nipple and areola by shave excision.
AB  - The case is presented of a 29-year-old female who, at the age of 13 years,
      developed bilateral verrucous thickening of her areolae. Despite the condition
      causing her significant psychosocial morbidity, a specialist referral was
      initially denied on the grounds that no treatment was apparently available. The
      condition progressively deteriorated over the subsequent 14 years. She was
      eventually referred for a dermatology opinion, and the diagnosis of nevoid
      hyperkeratosis was made. Topical therapy with keratolytics was unsuccessful, and
      she was referred for a plastic surgery review. Bilateral shave excision of the
      lesion was performed under general anesthesia, with a satisfactory outcome and no
      evidence of recurrence at 10 months.

PMID- 15502473
TI  - Primum non nocere.

PMID- 15502474
TI  - The economic burden of dry eye: a conceptual framework and preliminary
      assessment.
AB  - PURPOSE: To develop a conceptual framework for analyzing the economic burden of
      dry eye and a preliminary assessment of key factors that contribute to that
      burden. METHODS: The MEDLINE database was searched from 1966 to May 2003
      combining the term "dry eye" with various economic terms. In addition, individual
      interviews with a panel of clinicians were conducted to provide additional
      insight on resource use. RESULTS: Direct resource utilization among dry eye
      sufferers includes healthcare professional visits, nonpharmacological therapies,
      pharmacological treatments, and surgical procedures, with the latter 2 categories
      being the major cost drivers. Complementary and alternative medicine (CAM)
      therapies are a newly recognized component of the dry eye economic burden. There
      is wide variation in patterns of diagnosis and treatment, but current therapies
      are not universally effective. Given the prevalence of the condition, indirect
      costs may be large. Utilization of pharmacological therapies, especially those
      other than tear replacements, the extent of CAM use, cost of complications of
      surgical procedures, and indirect costs are unknown. The natural history and
      probability that patients will transition between therapies, based on underlying
      disease severity, need to be elucidated. CONCLUSIONS: Dry eye is a prevalent
      condition with the potential for a high economic burden; additional studies are
      needed to further characterize the economic impact.

PMID- 15502475
TI  - The lack of association between signs and symptoms in patients with dry eye
      disease.
AB  - BACKGROUND: The purpose of this report was to examine the relation between
      clinical tests and dry eye symptoms in patients with dry eye disease. METHODS:
      Seventy-five patients with dry eye disease (ICD-9 code 375.15) were included in
      these analyses. There was no specific entry criterion for enrollment in addition
      to a previous dry eye diagnosis in this clinic-based sample. Patients represented
      varying types and severity of dry eye disease and were previously diagnosed by
      clinic attending doctors in this university clinic setting. The study examination
      included a symptom interview that assessed dryness, grittiness, soreness,
      redness, and ocular fatigue. The interview was followed by a clinical dry eye
      examination conducted in the following sequence: meibomian gland assessment, tear
      meniscus height, tear breakup time test, fluorescein staining, the phenol red
      thread test, Schirmer test, and rose bengal staining. Partial Spearman
      correlation coefficients, the Wilcoxon rank sum test, chi 2 test, and
      multivariate logistic regression were used to evaluate the relationship between
      dry eye tests and symptoms. RESULTS: Symptoms were generally not associated with
      clinical signs in patients with dry eye disease. There were no significant
      correlations between signs and symptoms after adjustment for age and artificial
      tear use. The rank of each clinical test result did not statistically differ when
      stratified by the presence of patient symptoms in Wilcoxon rank sum analyses.
      Likewise, the frequency of patient symptoms did not differ statistically when
      stratified by a positive clinical test result in chi 2 analyses. In multivariate
      logistic regression analyses, no clinical test significantly predicted frequently
      reported symptoms after adjustment for age and artificial tear use. CONCLUSIONS:
      These results suggest a poor relation between dry eye tests and symptoms, which
      represents a quandary in dry eye clinical research and practice.

PMID- 15502476
TI  - Increased eotaxin in tears of patients wearing contact lenses.
AB  - PURPOSE: Giant papillary conjunctivitis in patients wearing contact lenses occurs
      after intolerance and/or allergy to contact lenses. Eotaxin is a CC chemokine
      with a potent and specific chemotactic effect for eosinophils, which are involved
      in allergies. The purpose of this study is to measure the eotaxin levels in tears
      of patients wearing contact lenses and in normal subjects. Eotaxin levels were
      also correlated with the grade of giant papillary conjunctivitis. METHODS: Around
      10 microL of tears were collected with glass capillaries in 16 patients wearing
      contact lenses and in 10 normal volunteers. Giant papillary conjunctivitis was
      graded from 0 to 4 by reference to standard slit-lamp photographs of the superior
      tarsal conjunctiva. Eotaxin concentration in tears was measured by ELISA using
      mouse anti-human eotaxin monoclonal antibodies. For the statistical analysis of
      the results, the paired Wilcoxon/Kruskal-Wallis test was used. RESULTS: The mean
      concentration of eotaxin was 2698+/-233 (SEM) pg/mL in patients wearing contact
      lenses and 1498+/-139 pg/mL in normal subjects. The difference was statistically
      significant (P=0.0004). The mean score of papilla grade was 1.75+/-0.19 in
      patients wearing contact lenses and 0.2+/-0.13 in normal subjects (P<0.0001).
      Papilla grade could be correlated to the eotaxin level in tears (R2=0.6562 and
      P<0.0001). CONCLUSION: An increase of eotaxin levels in tears was measured in
      patients wearing contact lenses. Eotaxin levels correlated with the severity of
      giant papillary conjunctivitis. These data suggest that eotaxin could play a role
      in papilla formation.

PMID- 15502477
TI  - Globe rupture following penetrating keratoplasty: how often, why, and what can we
      do to prevent it?
AB  - PURPOSE: Traumatic globe rupture following penetrating keratoplasty is a life
      long postoperative concern. We look at a series of penetrating keratoplasties in
      one institution and determine the rates of traumatic rupture and the outcomes
      following rupture. The reasons for persisting wound weakness are reviewed, and
      recommendations for eye protection based on wound strength are given. METHODS: A
      case-control study compared the postsurgical rupture rates for all cases of
      penetrating keratoplasty to those cases of globe rupture after extracapsular
      cataract surgery and phacoemulsification. A literature review of corneal wound
      healing was completed. RESULTS: Over 10 years 139 penetrating keratoplasties were
      performed. The incidence of traumatic rupture following keratoplasty was 5.8%.
      Fifty percent of those with ruptured globes had a visual outcome of hand movement
      vision or worse. Of the traumatic ruptures, 37.5% occurred in the first
      postoperative month. The indication for initial keratoplasty did not influence
      the rupture rate. In comparison, the general rate of penetrating eye injuries in
      the population was 2.2/100,000 per annum. The rupture rate for extracapsular
      cataract surgery was 1/221 (0.45%) and 0/6450 for phacoemulsification. Both of
      these rates were significantly less than after penetrating keratoplasty (P=0.005,
      P<0.0001). DISCUSSION: Penetrating keratoplasty cases have a higher rate of globe
      rupture than other ocular procedures. There are 5 important time periods of wound
      integrity after penetrating keratoplasty. The highest risk period is the month
      following surgery, when wound strength is derived almost entirely from sutures.
      The 18 months following surgery are moderately high risk. The month following
      removal of sutures is a second high-risk period. In the 6 months following this,
      the wound has a similar strength to the first postoperative year. Following
      penetrating keratoplasty the cornea never regains its preoperative strength and
      remains at risk for traumatic rupture for the remainder of the patient's life.

PMID- 15502478
TI  - Meibomianitis: polar lipid abnormalities.
AB  - PURPOSE: To determine abnormal meibomian gland secretion polar lipids from
      meibomianitis patients and to determine the significance of these lipid
      differences. METHODS: Meibomian gland secretions were collected from controls and
      patients with chronic blepharitis. These meibomian gland lipids (meibum) were
      first separated by thin-layer chromatography. Polar lipids were then separated
      utilizing high-pressure liquid chromatography with ultraviolet detection.
      Individual peaks were identified by comparison to standards and retention time.
      RESULTS: A polar lipid with an HPLC retention time longer than either
      phosphatidylcholine or sphingomyelin and shorter than phosphatidylethanolamine
      was significantly greater in the meibomianitis group (P<0.05) compared with other
      chronic blepharitis groups and normals. This polar lipid's retention time was
      similar to that of dimethylphosphatidylcholine or possibly
      lysophosphatidylcholine. Additionally, meibomianitis polar lipids' normal fatty
      acids were highly unsaturated and differed from those of other groups, none of
      which were unsaturated. CONCLUSION: Many of the most significant differences in
      meibomianitis meibum composition occur in the polar lipids rather than the
      nonpolar lipids. Further investigations will determine the true significance of
      these findings.

PMID- 15502479
TI  - Double-masked, placebo-controlled safety and efficacy trial of diquafosol
      tetrasodium (INS365) ophthalmic solution for the treatment of dry eye.
AB  - PURPOSE: To investigate the safety and efficacy of diquafosol tetrasodium, a P2Y2
      receptor agonist that stimulates fluid and mucin secretion on the ocular surface,
      as a novel topical treatment of dry eye disease. METHODS: Subjects with dry eye
      (n=527) were evaluated in a randomized, double-masked, parallel-group trial
      comparing 24 weeks of treatment with 2 concentrations of diquafosol (1% and 2%)
      versus placebo instilled 4 times daily. Corneal staining, conjunctival staining,
      Schirmer tests, and subjective symptoms of dry eye were evaluated. Use of
      artificial tears was permitted as necessary. RESULTS: Subjects treated with 2%
      diquafosol had significantly lower corneal staining scores compared with placebo
      at the 6-week, primary efficacy time point (P<0.001), and superiority continued
      throughout the 24-week study. Reductions in corneal staining were observed as
      early as after 2 weeks of treatment, were maintained throughout the 24-week
      study, and were observed to worsen slightly (toward baseline) when diquafosol
      treatment was discontinued (week 25). Results for conjunctival staining were
      consistent with those observed for corneal staining. Schirmer scores at week 6
      were significantly higher with diquafosol treatment than with placebo
      (P<or=0.030). The percentage of subjects with clearing of foreign body sensation
      (score of 0) was higher at week 6 in subjects treated with 2% diquafosol (21%)
      compared with placebo (15%), but the difference did not achieve significance
      (P=0.193). Significant differences in favor of diquafosol were observed for
      clearing of foreign body sensation and for worst symptom in secondary data
      analyses. CONCLUSION: Diquafosol tetrasodium was well tolerated and was superior
      to placebo (vehicle) in reducing corneal staining and in relieving certain
      patient symptoms. Diquafosol has a favorable risk/benefit profile in a broad
      spectrum of patients with dry eye disease and is a novel topical treatment of dry
      eye.

PMID- 15502480
TI  - Concurrent use of 5% natamycin and 2% econazole for the management of fungal
      keratitis.
AB  - PURPOSE: To determine if concurrent use of 5% natamycin and 2% econazole offers
      greater benefits than monotherapy with 5% natamycin for the management of fungal
      keratitis. METHODS: Subjects presenting to the cornea service were treated with
      5% natamycin and 2% econazole used concurrently. We compared the results with a
      historical control of patients treated with 5% natamycin in the same calendar
      year. The same clinical and examination protocol including inclusion and
      exclusion criteria was used for both groups. RESULTS: We compared results of 47
      subjects on concurrent use of 5% natamycin and 2% econazole with all 53 subjects
      who had received 5% natamycin in a previous study (historical controls). Baseline
      characteristics were similar between the 2 groups. There were no significant
      differences (P=0.9) between the 2 arms for success (defined as a healed or
      healing ulcer). CONCLUSIONS: Concurrent use of 5% natamycin and 2% econazole does
      not appear to offer additional benefits over monotherapy with 5% natamycin for
      the management of fungal keratitis.

PMID- 15502481
TI  - Electron microscopic study of anterior lens capsule allotransplants in chronic
      corneal ulcers.
AB  - PURPOSE: This study provides ultrastructural morphology and quantitative analysis
      of allotransplants of anterior lens capsule in the treatment of recurrent corneal
      ulcers. METHODS: Mechanical ulcers of uniform size were created with a 6-mm
      corneal trephine in 9 eyes at one-third corneal depth in 6 white New Zealand male
      rabbits. Following initial epithelial regrowth, an identical injury was created
      in the same area of each cornea a second time. In 6 eyes (treated group), an
      anterior lens capsule from a healthy donor rabbit was sutured into the ulcer bed,
      followed by antibiotic/steroid drops 3 times daily for 1 week. The remaining 3
      control eyes were allowed to heal without surgical intervention using the same
      antibiotic/steroid drops only. Slit-lamp examination, histopathology, and
      electron microscopic findings with hemidesmosome counts and size were recorded
      over a 3-month follow-up period. RESULTS: The control injured group had
      discontinuous epithelial basement membrane with significant reduction in
      hemidesmosome count compared with noninjured controls (P<0.0001). The treated
      subgroup 7 days after surgery showed linear basement membrane with identifiable
      lamina lucida and densa and newly-formed hemidesmosomes, which were significantly
      more numerous than in the injured but nontreated group (P<0.0001). Numerous
      hemidesmosomes and firm adhesion of epithelium to underlying stroma were seen in
      this group with lens capsule allografts 3 months after surgery. The number and
      size of hemidesmosomes did not significantly differ between groups 7 days and 3
      months after surgery. CONCLUSIONS: On the ultrastructural level, anterior lens
      capsule allotransplants in mechanically induced corneal ulcer heal with
      continuously formed epithelial basement membrane and numerous hemidesmosomes.
      This enables significant reformation of hemidesmosomes that are identical in size
      to hemidesmosomes in healthy corneas and helps forming a stronger apposition for
      epithelial cells to underlying structures in eyes where epithelial basement
      membrane has been destroyed from chronic ulceration.

PMID- 15502482
TI  - Ultrasound-enhanced transcorneal drug delivery.
AB  - PURPOSE: Ultrasound has been shown to enhance, by up to 10 times, the corneal
      permeability to different compounds such as beta-blockers and fluorescein. Here,
      we report on our investigation of the mechanisms of ultrasound-enhanced drug
      delivery through the cornea using light and electron microscopy. METHODS:
      Enhancement of permeability for a hydrophilic compound, sodium fluorescein, in
      rabbit cornea in vitro was achieved using ultrasound at a frequency of 880 kHz
      and intensities of 0.19-0.56 W/cm2 with an exposure duration of 5 minutes. Light
      and electron microscopy (transmission and scanning) were used to observe
      ultrasound-induced structural changes in the cornea. RESULTS: The permeability
      increased by 2.1, 2.5, and 4.2 times when ultrasound was applied at 0.19, 0.34,
      and 0.56 W/cm2, respectively (P<0.05). The surface cells of corneal epithelium
      exposed to ultrasound appeared swollen and lighter in color (indications of
      membrane rupture) as compared with the control cells. Some of the surface
      epithelial cells were absent. The cells in the inner layers of the epithelium
      were occasionally lighter in color. Also, holes 3-10 microm in diameter were
      observed on the epithelial surface. No structural changes were observed in the
      stroma. CONCLUSION: Ultrasound enhancement of drug delivery through the cornea
      appears to result from minor structural alterations in the epithelium. Careful
      investigation of the recovery of cornea structure and barrier function after the
      ultrasound application, in vivo, is needed.

PMID- 15502483
TI  - Expression of fibronectin isoforms bearing the alternatively spliced EIIIA,
      EIIIB, and V segments in corneal alkali burn and keratectomy wound models in the
      rat.
AB  - PURPOSE: To better understand the healing process in the wounded cornea,
      fibronectin (FN) isoforms bearing the alternatively spliced EIIIA, EIIIB, and V
      segments (EIIIA+, EIIIB+, and V+ FNs) were evaluated in alkali burn and
      keratectomy wound models in the rat. METHODS: Alkali burn or keratectomy wounds
      (both 2 mm) were created, and corneas were harvested at various time points and
      analyzed by indirect immunofluorescence using antibodies specific for the EIIIA,
      EIIIB, and V segments as well as for the total pool of FN (total FN). RESULTS:
      There was minimal staining for any variety of FN in the epithelium or basement
      membrane zone (BMZ) in normal cornea, but each antibody produced granular
      staining in the stroma. Bright staining for V+ and total FNs was evident at the
      denuded stromal surface 1 day following keratectomy. In contrast, staining for
      EIIIA+ and EIIIB+ FNs was negligible at 24 hours but appeared on the wound
      surface under the migrating unstained epithelium by the second day. BMZ staining
      for FN then gradually subsided, such that there was little or no staining by 6
      weeks. In contrast, alkali burn wounds exhibited very little BMZ staining
      throughout the time course. Although there was preferential staining of the
      anterior aspect of Descemet membrane by anti-EIIIA and anti-EIIIB antibodies
      under normal conditions, the staining intensity of the anterior and posterior
      aspects became similar following corneal wounding. CONCLUSION: Deposition of
      EIIIA+ and EIIIB+ FNs in the BMZ of the keratectomy wound occurs more slowly than
      deposition of V+ and total FNs. EIIIA+ FN is expressed in a distribution that
      overlaps with that previously described for the alpha 9 integrin subunit
      following corneal debridement, suggesting that EIIIA-alpha 9 interactions could
      occur during corneal wound healing. In contrast, the relative lack of FN
      deposition in alkali burn wounds suggests that proteolytic degradation of FN may
      occur; and this, along with impairment of new FN synthesis because of cellular
      damage, could play a role in the high prevalence of recurrent epithelial erosions
      in alkali-wounded corneas.

PMID- 15502484
TI  - Ocular cicatricial pemphigoid, keratomycosis, and intravenous immunoglobulin
      therapy.
AB  - PURPOSE: To report the case of a patient developing fungal keratitis in the
      context of uncontrolled ocular cicatricial pemphigoid (OCP), which, despite
      intravenous immunoglobulin (IVIg) and other immunomodulatory therapy, progressed
      to end-stage pemphigoid, with corneal opacification, ankyloblepharon, and
      xerosis. Keratoprosthesis (KPro) restored functional vision for the patient.
      METHODS: A 39-year-old man presented with uncontrolled CP and corneal ulcer in
      the left eye. Conjunctival biopsy diagnosed OCP; corneal scraping and biopsy
      diagnosed the cause of the corneal ulcer. OCP was treated with systemic steroids,
      immunosuppressive drugs, and IVIg. Visual rehabilitation was accomplished with
      Ahmed valve and a type II Dohlman KPro. RESULTS: Immunohistology of the biopsied
      conjunctiva showed IgG at the epithelial basement membrane zone, confirming the
      clinical diagnosis of OCP. Microbiologic studies of the corneal biopsy specimen
      were negative for Acanthamoeba and herpes but positive for Aspergillus niger. The
      patient's keratomycosis resolved with topical antifungal therapy. Treatment with
      Dapsone, intravenous-pulse steroid, oral cyclophosphamide, and intravenous
      immunoglobulin (IVIg) failed to control the OCP, with resultant complete
      conjunctivization of the cornea. Keratoprosthesis improved the patient's visual
      acuity from hand movements to 20/20. CONCLUSIONS: Patients with uncontrolled OCP
      are at increased risk of corneal infection. The difficulty in diagnosing
      keratomycosis and the relatively rare occurrence of OCP explain the uniqueness of
      our reported case. OCP may progress to "end-stage" disease despite therapy.
      Keratoprosthesis can restore vision in selected otherwise seemingly hopeless
      cases.

PMID- 15502485
TI  - Reversible amantadine-induced corneal edema in an adolescent.
AB  - PURPOSE: To document reversible corneal edema caused by amantadine in a pediatric
      patient. METHODS: A 14-year-old boy with a neurologic tremor was referred for
      bilateral visual loss. Our examination disclosed bilateral corneal edema without
      ocular inflammation. Pachymetry confirmed significantly increased corneal
      thickness above 900 microm. RESULTS: Review of the patient's medical information
      revealed recent institution of amantadine as a means to control the patient's
      tremor. On cessation of this agent, rapid resolution of corneal edema and
      recovery of visual acuity occurred. Repeat pachymetry measurement revealed normal
      corneal thickness. CONCLUSION: In cases of corneal edema and in the absence of
      any identifiable ocular causes, a review of toxic effects of systemic medication
      should be undertaken. Amantadine can cause corneal decompensation and needs to be
      considered as part of the differential diagnosis of corneal edema.

PMID- 15502486
TI  - Confocal microscopy and corneal sensitivity in a patient with corneal
      manifestations of Tangier disease.
AB  - PURPOSE: Tangier disease is an autosomal recessive disorder in which cholesterol
      rich lipids are deposited at various tissues of the body including the cornea. In
      this case report, the corneal changes in a patient with Tangier disease are
      described. METHODS: A 72-year-old patient who was diagnosed with Tangier disease
      25 years before received a complete eye examination including confocal microscopy
      and Cochet-Bonnet esthesiometry. RESULTS: Slit-lamp biomicroscopy and confocal
      microscopy showed bilateral corneal opacifications caused by lipid accumulation.
      Confocal microscopy showed that pathologic changes in the cornea in Tangier
      disease are limited to the stroma. Neither a reduced corneal sensation nor lid
      abnormalities as previously described in Tangier disease were found. CONCLUSION:
      Confocal microscopy helps to identify corneal changes in the stroma caused by
      Tangier disease easily missed in a slit-lamp examination. The ocular
      manifestations of Tangier disease do not necessarily include a reduced corneal
      sensitivity and lid abnormalities.

PMID- 15502487
TI  - Treatment of atopic eyelid disease using topical tacrolimus following
      corticosteroid discontinuation in a patient with open-angle glaucoma.
AB  - PURPOSE: To report a case of atopic eyelid disease treatment using topical
      tacrolimus in a patient with open-angle glaucoma following corticosteroid
      discontinuation. DESIGN: Interventional case report. METHODS: A 59-year-old white
      man with a history of treated open-angle glaucoma (latanoprost 0.005%) was
      referred to our department for atopic eyelid disease. The patient had received
      previous treatment with topical corticosteroid ointments (hydrocortisone acetate
      1%/dexamethasone 0.1% ointments) that, even though they were effective in
      controlling atopic eyelid disease, were complicated by markedly elevated
      intraocular pressure (IOP) (steroid responder). Topical steroids were
      discontinued while other treatment modalities (such as eyelid hygiene, artificial
      tears, topical antihistamine drugs, topical mast cell stabilizers, or
      topical/oral antibiotics) were proven ineffective. RESULTS: Topical tacrolimus
      0.03% ointment (Protopic; Fujisawa, Dublin, Ireland) was applied to the eyelid
      skin twice daily. An improvement of eyelid inflammation was observed while
      eczematous skin lesions and erosions were resolved within 15 days. After 6 months
      of continued topical tacrolimus treatment, there was no evidence of atopic
      dermatitis recurrence. During this period IOP remained controlled without any
      evidence of deregulation. CONCLUSIONS: Treatment of atopic eyelid disease with
      topical tacrolimus, following corticosteroid discontinuation in a steroid
      responder patient with open-angle glaucoma, seems to be an effective alternative
      treatment to corticosteroids without the risk of IOP increase.

PMID- 15502488
TI  - Reverse ptosis-induced corneal steepening and decreased vision after LASIK
      surgery.
AB  - PURPOSE: To report a patient with a past history of LASIK who had decreased
      vision and induced corneal steepening after lower eyelid ptosis. Surgical
      correction of lower eyelid ptosis decreased the corneal steepening and improved
      visual acuity. METHODS: Interventional case report. RESULTS: A 37-year-old woman
      had a history of bilateral LASIK, childhood strabismus surgery, and multiple
      surgeries to release scarring and improve motility in her left eye. Last surgery
      to release scar tissue resulted in reverse ptosis (lower eyelid ptosis) and
      decreased visual acuity from induced corneal steepening. Correction of lower
      eyelid ptosis by reinsertion of the retractor complex resulted in decreasing
      corneal steepening, improved visual acuity, and good anatomic position of the
      lower eyelid. CONCLUSION: Lower eyelid ptosis may induce corneal steepening and
      decreased vision after LASIK. Surgical correction of ptosis can decrease the
      extent of steepening and improve visual acuity.

PMID- 15502489
TI  - Combined mitomycin C application and free flap conjunctival autograft in
      pterygium surgery.

PMID- 15502496
TI  - Timing of aortic surgery in the Marfan syndrome.

PMID- 15502497
TI  - Stent graft treatment for abdominal aortic aneurysm repair: recent developments
      in therapy.
AB  - PURPOSE OF REVIEW: Minimally invasive endovascular techniques for the treatment
      of abdominal aortic aneurysms have significantly reduced the morbidity of these
      procedures compared with standard surgical repair. In addition, patients with
      extensive comorbid medical illnesses in whom standard operative repair is
      contraindicated may be successfully treated using endovascular means. RECENT
      FINDINGS: Recently, several important developments have significantly advanced
      this area of treatment. The Food and Drug Administration has approved four
      endovascular stent grafts for the treatment of abdominal aortic aneurysms: the
      Medtronic AneuRx, the W.L. Gore Excluder, the Cook Zenith, and the Guidant
      Ancure. The Zenith received approval for marketing in 2003 and has gained
      relatively wide use, in part because of its ability to treat aneurysms with
      relatively large-diameter implantations zones. Also in 2003, Guidant Corporation
      withdrew the Ancure graft from marketing and distribution. The withdrawal was
      influenced by difficulties encountered using the graft's delivery system and
      improper reporting to the Food and Drug Administration. Enrollment has also been
      recently completed for the phase II Food and Drug Administration trials of the
      Medtronic Talent graft and the Cordis Fortron graft. These devices have been
      approved for use in the European Union and are awaiting Food and Drug
      Administration panel meeting in the United States. Several significant advances
      have also occurred recently in stent graft research and development. Of
      particular significance has been the initiation of the phase I trial of the
      Trivascular Enovus graft. Deployment of the Trivascular graft may be accomplished
      through a delivery system that is considerably reduced in profile. The potential
      for percutaneous application of the graft may be available in the future. In
      selecting the specific stent graft to be used for endovascular abdominal aortic
      aneurysm repair, the specific graft characteristics must be considered,
      particularly with regard to the individual patient's anatomic and physiologic
      characteristics. Comparative analysis of the several of the various stent grafts
      has been performed. Results have varied with regard to the need for secondary
      interventions, aneurysm sac size reduction, and the occurrence of continued
      perfusion of the aneurysm sac. In addition, the indications for use of
      endovascular grafts compared with standard open surgery have not yet been fully
      defined. SUMMARY: This article describes the general principles of use for
      endovascular devices for the repair of abdominal aortic aneurysms. It details the
      features and results for the devices in current use, and highlights the recent
      developments in stent graft treatment of abdominal aortic aneurysms.

PMID- 15502498
TI  - Biomarkers in pulmonary embolism.
AB  - PURPOSE OF REVIEW: Controversy exists about the precise role of thrombolytic
      therapy in normotensive patients with pulmonary embolism. To resolve this
      controversy two major questions must be addressed. First, can a subgroup of
      normotensive pulmonary embolism patients with a high risk for adverse outcomes,
      such as in-hospital mortality or early recurrent venous thromboembolism, be
      identified? Second, is there convincing evidence that the benefits of more
      aggressive therapy counterbalance its risks?Troponin I and T as well as brain
      natriuretic peptide (BNP) have recently been introduced as promising tools in the
      risk assessment of patients with pulmonary embolism. RECENT FINDINGS: The studies
      in series of patients with pulmonary embolism showed prevalences of elevated
      cardiac biomarkers of 16 to 84%. Positive predictive values for in-hospital
      mortality varied from 6 to 44%, whereas negative predictive values for uneventful
      outcome were above 93% in all studies. SUMMARY: Although a correlation between
      elevated biomarkers and in-hospital mortality in pulmonary embolism patients is
      present in most of the studies, the positive predictive value appears to be
      insufficient to extend the indication for thrombolytic therapy to all patients
      with elevated biomarkers. Future research is necessary to show whether combining
      different biomarkers with echocardiography is more useful.

PMID- 15502499
TI  - Approach to the dilated aortic root.
AB  - PURPOSE OF REVIEW: The dilated aortic root is often completely asymptomatic and
      found incidentally on routine imaging studies such as chest radiograph,
      echocardiography, chest computed tomography, or magnetic resonance imaging. The
      dilated aortic root may be associated with underlying aortic valve abnormalities
      as seen with bicuspid aortic valve. It may also lead to the awareness of
      important underlying connective tissue disorders like the Marfan syndrome. It is
      imperative that the dilated aortic root be observed carefully over time with
      serial imaging studies and that timely resection of the aneurysm be carried out
      before catastrophic complications such as aortic dissection, aortic rupture, or
      congestive heart failure from aortic insufficiency occur. RECENT FINDINGS: In
      recent years, the advent of molecular genetics has heightened awareness of
      familial aortic disease such as the Marfan syndrome, bicuspid aortic valve
      disease, and hereditary aortic aneurysm and dissection. In addition to
      hypertension and inflammatory aortic disease, these hereditary aortopathies are
      important to consider in the evaluation of patients with a dilated aorta and have
      implications for screening of the relatives of the patient with aortic aneurysm.
      SUMMARY: Because there is often uncertainty regarding the dilated aortic root,
      this review will summarize the approach to diagnosis, evaluation, and management
      of aortic root aneurysms. Clinical features, diagnostic approaches, screening of
      relatives, and long term follow-up will be highlighted.

PMID- 15502500
TI  - Venous thromboembolism prophylaxis in medical patients.
AB  - PURPOSE OF REVIEW: Venous thromboembolism, including deep vein thrombosis and
      pulmonary embolism, represents a significant source of morbidity and mortality in
      the United States and worldwide. Most acutely ill medical patients are at risk
      for venous thromboembolism, and prophylaxis is recommended. However, acutely ill
      medical patients are heterogeneous, and the degrees of risk, the length of
      prophylaxis, as well as the most safe and efficacious strategies to prevent
      venous thromboembolism in specific medical patients continue to evolve. RECENT
      FINDINGS: Most medically ill patients in the hospital do not receive any form of
      venous thromboembolism prophylaxis despite evidence that their venous
      thromboembolism risk is similar to surgical patients. Low-molecular weight
      heparins demonstrate at least equal efficacy and improved safety over standard
      unfractionated heparin for the prevention of venous thromboembolism in medical
      patients. Patients with renal impairment, obesity, or those who are critically
      ill are special populations for prophylaxis that require individual approaches.
      Many patients recently discharged from the hospital remain at high risk for
      thrombosis. SUMMARY: All hospitalized patients should be assessed for venous
      thromboembolism risk. Most acutely ill medical patients will be in the high- to
      very high-risk category for thrombosis. Patients who have an estimated thrombosis
      risk greater than bleeding risk should receive pharmacologic prophylaxis. Low
      molecular weight heparin is the preferred drug-based approach over standard
      unfractionated heparin for the prevention of venous thromboembolism in the
      acutely ill medical patient. Patients with higher risks for bleeding than
      thrombosis should receive mechanical methods of prophylaxis. Patients who have
      not returned to baseline health should be considered for extended venous
      thromboembolism prophylaxis out of the hospital.

PMID- 15502501
TI  - Evaluation of pulmonary arterial hypertension.
AB  - PURPOSE OF REVIEW: Pulmonary arterial hypertension (PAH) is defined as a group of
      diseases characterized by a progressive increase of pulmonary vascular resistance
      leading to right ventricular failure and premature death. The purpose of this
      review is to analyze the current knowledge of the evaluation of PAH patients.
      RECENT FINDINGS: Recently, the diagnostic approach has been more clearly defined
      according to the new clinical classification and with consensus reached on
      algorithms of various investigative tests and procedures that exclude other
      causes and ensure an accurate diagnosis of PAH. The diagnostic procedures include
      clinical history and physical examination, ECG, chest radiography, transthoracic
      Doppler echocardiography, pulmonary function tests, arterial blood gases,
      ventilation and perfusion lung scan, high-resolution CT of the lung, contrast
      enhanced spiral CT of the lung and pulmonary angiography, blood tests and
      immunology, abdominal ultrasound scan, exercise capacity assessment, and
      hemodynamic evaluation. SUMMARY: Invasive and noninvasive markers of disease
      severity, either biomarkers or physiologic parameters and tests that can be
      widely applied, have been proposed to reliably diagnose PAH and monitor the
      clinical course.

PMID- 15502502
TI  - Percutaneous intervention for renovascular disease: rationale and patient
      selection.
AB  - PURPOSE OF REVIEW: The anatomic diagnosis of renovascular disease is increasing
      in frequency due to the advent of sophisticated non-invasive imaging modalities
      such as MRA (Magnetic Resonance Angiography) and renal angiography at the time of
      cardiac catheterization. Despite this fact, the investigation and appropriate
      management of renovascular disease has remained a controversial topic. This
      review addresses the clinical syndromes associated with renal artery stenosis
      (RAS) and the published data guiding appropriate patient selection for
      revascularization. RECENT FINDINGS: There is a growing literature in support of
      renal revascularization as an aid in improving anti-hypertensive control,
      preserving renal function, and easing the management of congestive heart failure.
      Meanwhile, technological advances have allowed intervention in an expanding pool
      of eligible patients. One such technology is the atheroembolic protection device,
      which may soon allow renal salvage in patients with significant baseline renal
      impairment that were previously denied intervention for fear of worsening renal
      function. SUMMARY: The data reviewed herein helps to identify patients that will
      benefit from renal revascularization. Large-scale, randomized data further
      defining the role of renal revascularization and optimal patient selection is
      still needed.

PMID- 15502503
TI  - Surgical coronary revascularization remains relevant in the era of stents.
AB  - PURPOSE OF REVIEW: The high prevalence of coronary artery disease (CAD) has
      inspired the development of technologies and techniques for coronary
      revascularization, including coronary artery bypass grafting (CABG) and catheter
      based interventions (CBIs). RECENT FINDINGS: Although CBIs allow the avoidance of
      general anesthesia, sternotomy, and cardiopulmonary bypass, CBIs-including those
      performed using drug-eluting stents-are associated with much higher rates of
      vascular reocclusion than is CABG. In addition, CBIs are not well suited to
      patients with diabetes or chronic total occlusion, both of which are extremely
      common in the CAD population. In contrast, CABG has proven effective for CAD
      patients with these conditions. The technology used in CABG continues to improve;
      ongoing innovations include off-pump coronary artery bypass; gene therapy to
      prevent restenosis; and endoscopic, video-assisted, and robot-assisted CABG using
      automated one-shot distal anastomotic devices. SUMMARY: Although CBIs for CAD are
      now performed more often than surgical procedures, surgery remains an important
      treatment option.

PMID- 15502504
TI  - New devices for percutaneous coronary intervention are rapidly making bypass
      surgery obsolete.
AB  - PURPOSE OF REVIEW: This review summarizes recent and cumulative progress in the
      success, safety, applicability, and durability of percutaneous coronary
      intervention. RECENT FINDINGS: Improvements in basic percutaneous coronary
      intervention (PCI) equipment and the availability of bare metal stents in the mid
      1990s improved acute procedural success to 98%, reduced the emergency surgery
      rate to 0.2%, and reduced the incidence of recurrent symptoms due to restenosis
      at the treated site to 15 to 20%. The recent availability of drug-eluting stents
      has reduced the in-stent neointimal proliferation that causes restenosis and
      reduced the incidence of symptomatic recurrence to less than 5%, rivaling that of
      bypass surgery. The work on better antithrombotic pharmacology, distal embolic
      protection, and devices for crossing chronic total occlusions will further add to
      the armamentarium for catheter-based revascularization. SUMMARY: Based on
      progress over the past decade, PCI has grown to represent about two-thirds of all
      coronary revascularization (800,000 PCI vs 350,000 bypass surgeries). Recent and
      ongoing progress will make bypass surgery largely obsolete within the next
      several years.

PMID- 15502505
TI  - Drug-eluting stents have made brachytherapy obsolete.
AB  - PURPOSE OF REVIEW: This manuscript reviews the controversy regarding the role of
      intravascular brachytherapy in the setting of growing use of drug eluting stents.
      The utility of intravascular brachytherapy is being rethought in relation to its
      use after the placement of drug eluting stents. Even with in-stent stenosis, the
      role of intravascular brachytherapy is decreasing primarily due to the simplicity
      of placement of drug eluting stents and the complexity of performing
      intravascular brachytherapy. RECENT FINDINGS: The impact of drug eluting stents
      is already decreasing the clinical impact of in-stent stenosis. The published
      pivotal clinical restenosis rates from both the Pacitaxil (TAXUS IV) and
      Sirolimus (SIRIUS) drug eluting stents suggests that the need to perform
      intravascular brachytherapy will be in fewer than one in 20 patients. Recently
      reported registry data from Europe and the United states demonstrates the
      equivalence drug eluting stent implantation to intravascular brachytherapy for in
      stent stenosis of bare metal stents. The role of intravascular brachytherapy for
      in-stent stenosis of drug eluting stents is very much in question. SUMMARY: This
      manuscript reviews the impact of Drug Eluting Stents in the practice of
      interventional cardiology and suggests that the need for intravascular
      brachytherapy will significantly decrease. Whether we will need this therapy at
      all is very controversial.

PMID- 15502506
TI  - Brachytherapy for restenosis after stenting for coronary artery disease: its role
      in the drug-eluting stent era.
AB  - PURPOSE OF REVIEW: Recent years have brought remarkable changes to the field of
      interventional cardiology. The need for repeat intervention due to restenosis,
      the most vexing long-term failure of percutaneous coronary intervention, has been
      significantly reduced owing to the introduction of two major advances, the
      vascular brachytherapy (VBT) and the drug-eluting stents (DES). RECENT FINDINGS:
      Vascular brachytherapy has demonstrated its efficacy in limiting recurrence of
      existing in-stent restenosis. The past 2 years have sealed its reputation, with a
      variety of studies demonstrating its superiority over conventional therapy in
      challenging patient subsets with high risk for restenosis recurrence. Moreover,
      the long-term follow-up confirmed durability of this therapy, and the failures of
      VBT were characterized as easy to treat. Conversely, DES have shown spectacular
      efficacy at primarily preventing the first restenosis episode following the
      initial stent placement. Consequently, the role of VBT may be minimized, as the
      overall need for repeat revascularization is diminished as a result of the wide
      acceptance of DES. Furthermore, if the capacity of DES to treat in-stent
      restenosis is confirmed in randomized trials, they may eventually supersede VBT
      as the therapy of choice for in-stent restenosis. SUMMARY: At present, VBT is the
      proven and durable therapeutic choice for patients with complex, diffuse in-stent
      restenosis who would otherwise have a very poor prognosis for long-term event
      free survival. DES have emerged as remarkably effective in minimizing the first
      restenosis occurrence; they also represent a promising and competitive
      alternative to VBT for the treatment of in-stent restenosis.

PMID- 15502507
TI  - Management strategies for cardiogenic shock.
AB  - PURPOSE OF REVIEW: Cardiogenic shock remains the most serious complication of
      acute MI, with an incidence of 6 to 8% and a 30-day mortality rate that remains
      close to 50%. While cardiogenic shock is due primarily to left ventricular
      failure, other causes such as acute mitral regurgitation and ventricular septal
      rupture must always be considered as emergency surgery may be life saving. The
      purpose of this review is to summarize recent advances in the care of these
      critically ill patients including the consideration of etiology and
      pathophysiology as well as the influence of age and adjunctive therapies. RECENT
      FINDINGS: Early revascularization is now an American College of
      Cardiology/American Heart Association guideline class 1 indication for
      percutaneous coronary intervention (PCI) particularly for younger patients in
      cardiogenic shock. Recent studies suggest there may also be a benefit in elderly
      patients with cardiogenic shock. SUMMARY: Prompt triage of all patients in
      cardiogenic shock for early angiography, intra-aortic balloon pump
      counterpulsation, and early revascularization with PCI or bypass surgery is now
      the preferred management strategy.

PMID- 15502508
TI  - Left ventricular assist devices: evolving devices and indications for use in
      ischemic heart disease.
AB  - PURPOSE OF REVIEW: The mortality with end-stage heart failure is extremely high,
      especially when patients become refractory to conventional medical therapy and
      require frequent hospitalization. Ischemic heart disease remains the primary
      cause of advanced heart failure. Mechanical pumps or devices have been developed
      called ventricular assist devices and are being used to support an increasing
      number of patients with refractory heart failure. RECENT FINDINGS: The use of
      ventricular assist devices has evolved from initially only support of patients
      unable to be weaned from a heart-lung machine after cardiac surgery to use now as
      a bridge to a heart transplant, including patients with acute myocardial
      infarction and shock and severe pulmonary hypertension. More recently, they have
      been proven as a definitive alternative for patients not eligible for heart
      transplantation. There are new devices being examined in clinical trials,
      including a change from pusher-plate to devices with axial flow technology that
      are much smaller and easier to implant. Outcomes with their use are improving
      rapidly as the devices become more reliable and more is learned about the
      importance of candidate selection. SUMMARY: This review describes current
      indications for the use of these devices, the types of pumps now available,
      criteria for initiating ventricular assist device support, complications of their
      use, and new applications such as a platform for stem cell therapy for treatment
      of end-stage heart failure.

PMID- 15502509
TI  - Implantable cardioverter defibrillator therapy in postinfarction patients.
AB  - PURPOSE OF REVIEW: In the past few years, new clinical trials were conducted to
      determine the effectiveness of implantable cardioverter defibrillators (ICDs) for
      prevention of mortality in patients with ischemic and nonischemic
      cardiomyopathies. This paper aims to provide an overview of the current state of
      knowledge regarding ICD therapy in postinfarction patients. RECENT FINDINGS:
      Postinfarction patients with severe left ventricular dysfunction are at high risk
      of sudden cardiac death. Antiarrhythmic therapy does not improve survival in such
      patients and, therefore, ICDs emerged as treatment of choice for both primary and
      secondary prevention of mortality after MI. The MADIT (Multicenter Automatic
      Defibrillator Implantation Trial) and MUSTT (Multicenter Unsustained Tachycardia
      Trial) trials were the first primary prevention ICD trials documenting a
      substantial reduction in mortality with an ICD in postinfarction patients with
      depressed ejection fraction, nonsustained ventricular tachycardia, and inducible
      sustained ventricular tachycardia. The recently completed MADIT II trial
      broadened indications for prophylactic use of ICD in postinfarction patients with
      ejection fraction of 30% or less without a requirement for additional risk
      stratifiers. The benefit from ICD therapy in patients with low ejection fraction
      was recently confirmed by results from the SCD-HeFT (Sudden Cardiac Death in
      Heart Failure) and COMPANION (Comparison of Medical Therapy, Pacing, and
      Defibrillation in Heart Failure) trials. SUMMARY: Recent clinical trials
      established ICD as an important therapeutic modality for primary and secondary
      prevention of mortality in postinfarction patients.

PMID- 15502510
TI  - Global patterns of health care for acute coronary syndromes.
AB  - PURPOSE OF REVIEW: Despite similar guidelines, remarkable global differences
      exist in the management of acute coronary syndromes. This review describes recent
      insights in global patterns of patient baseline characteristics, treatment
      strategies, medication use, and outcome in acute coronary syndromes. RECENT
      FINDINGS: Results from recent registries and randomized clinical trials suggest
      that the arrival of many novel medications and treatment options for acute
      coronary syndromes has led to interregional heterogeneity in the management and
      treatment of patients with acute coronary syndromes. These differences in health
      care and adherence to national and international guidelines appear to be
      influenced by geographical, social, cultural, and economic factors, resulting in
      regional variation in hospital characteristics, physician attitude, access to
      resources or advanced cardiovascular care, access to the literature, and the
      availability of drugs. SUMMARY: Significant differences in diagnosis and
      treatment of acute coronary syndrome patients can be observed globally, despite
      similar guidelines based on the same randomized clinical trials. Guidelines are
      not adapted promptly worldwide, influencing outcome and health care expenditure.

PMID- 15502511
TI  - Partial restoration of myocardial function and perfusion by cell therapy
      following myocardial infarction.
AB  - PURPOSE OF REVIEW: In animals, both skeletal myoblasts and stem cells partially
      restore myocardial function after MI. This review provides a critical analysis of
      the initial clinical trials of these two therapeutic strategies. RECENT FINDINGS:
      Direct injection of autologous skeletal myoblasts into the peri-infarct area has
      been performed at bypass surgery and by subendocardial injection in the
      catheterization laboratory. Both approaches appear to improve function
      significantly. Nonetheless, ventricular arrhythmias occur quite frequently in the
      first week after myoblast injection. In contrast, stem cells can be delivered to
      the injured myocardium by direct injection, by IV injection, or by bone marrow
      stimulation. The incidence of ventricular arrhythmia does not seem to increase.
      The magnitude of absolute improvement in cardiac ejection fraction, however, is
      only about 7%. The potential limitations of stem cell therapy are cell fusion,
      creating genetically abnormal cells, and the ability to deliver sufficient
      numbers of cells to have an important biologic effect. SUMMARY: Cell replacement
      therapy after MI has considerable promise for restoration of cardiac function.
      Nonetheless because important theoretical and practical questions remain
      unanswered, the methodology is not yet ready for widespread clinical application.

PMID- 15502513
TI  - Giving voice to a silent disease.

PMID- 15502514
TI  - The Minnesota tube: its use and care in bleeding esophageal and gastric varices.
AB  - A variety of treatments are available for bleeding esophageal varices. Treatments
      include pharmacologic (propanolol, somatostatin, octreotide, vasopressin, and
      nitroglycerin), endoscopic (injection sclerotherapy and banding), vascular
      (transjugular intrahepatic portosystemic shunt), surgical (portovariceal
      disconnection and portosystemic shunts), and tamponade (via use of the Minnesota
      tube). This article will focus on use and care of the Minnesota tube, including
      numerous suggestions from the literature. Tamponade for treatment of esophageal
      varices may be accompanied by numerous complications, some of which are major or
      lethal. For this reason, extreme caution should be used when implementing this
      method. While hemostasis is not achievable via tamponade in 8-50% of patients and
      50% of patients rebleed, use of tamponade may achieve stabilization of a patient
      so that sclerotherapy or surgery becomes a treatment option.

PMID- 15502516
TI  - The advanced practice nurse in gastroenterology serving as patient educator.
AB  - The role of the advanced practice nurse is evolving in the specialty of
      gastroenterology, requiring flexibility and an openness to change on the part of
      the practitioner. The gastroenterology advanced practice nurse performs history
      and physical assessments, orders diagnostic studies, determines medical and
      nursing diagnoses, prescribes and evaluates pharmacologic and other therapeutic
      regimens, manages followup care, and evaluates patient outcomes. The advance
      practice nurse also provides patient, family, and group education and screening
      programs. Collaboration with other healthcare professionals; serving as a mentor
      and as a consultant; participating in continuing education, research and quality
      management; and providing professional leadership underscore the professional
      aspects of advance practice nurse activities. The focus of this article is the
      educational role of the advanced practice nurse. The body of knowledge applicable
      to the educational role is discussed, in addition to contributory professional
      activities.

PMID- 15502517
TI  - Statement on nursing: a personal perspective.
AB  - Contemporary nursing is based on a conglomerate of theoretical nursing models.
      These models each incorporate four central concepts: person, health, environment,
      and nursing. By defining these concepts, nurses develop an individual framework
      from which they base their nursing practice. As an aspiring nurse practitioner in
      the gastroenterology field, I have retrospectively assessed my personal
      definitions of person, health, environment, and nursing. From these definitions,
      I am able to incorporate specific theoretical frameworks into my personal belief
      system, thus formulating a basis for my nursing practice. This foundation is
      comprised of the influence of nursing theorists Jean Watson, Sister Callista Roy,
      Kolcaba, Florence Nightingale, and Ida J. Orlando; the Perioperative Patient
      Focused Model; Watson's Theory of Human Caring; theories regarding transpersonal
      human caring and healing; and feminist theories. Therefore, this article
      describes self-examination of nursing care by defining central nursing concepts,
      acknowledging the influence of nursing theorists and theories, and developing a
      personal framework from which I base my nursing practice.

PMID- 15502518
TI  - Chronic hepatitis C virus and the Hispanic community: cultural factors impacting
      care.
AB  - Hispanics are one of the fastest growing ethnic minorities in the United States.
      Estimates suggest there are 32.8 million Hispanics in the United States,
      comprising 12% of the population. Hispanics have a 40% greater chance of being
      infected with hepatitis C virus than the general population. In fact, chronic
      liver disease is the seventh highest cause of death in Hispanics, ages 25 to 44,
      and third highest in the 45 to 64 age group.

PMID- 15502519
TI  - Living with hepatitis C: a nurse's story.
AB  - Nearly 4 million people in the United States are infected with the hepatitis C
      virus, which already has caused 8,000 to 10,000 deaths annually. The morbidity
      may increase to 30,000 in the next two decades. Currently, in the nursing and
      healthcare literature, there is little information regarding the actual
      experiences of people living with hepatitis C. To help meet that need, I would
      like to describe my personal experiences with hepatitis C as I transitioned from
      nurse to patient. This is the story of the beginning of my journey.

PMID- 15502521
TI  - Immediate impressions.

PMID- 15502520
TI  - Use of propofol in gastroenterology practice.

PMID- 15502522
TI  - C-reactive protein elevation and the risk of colorectal cancer.

PMID- 15502524
TI  - Is this a behavior problem or normal temperament?

PMID- 15502525
TI  - Disruptive classroom behavior in an amish school-age child with muscular
      dystrophy.

PMID- 15502526
TI  - Parental concerns about extended breastfeeding in a toddler.

PMID- 15502527
TI  - Preparing a 3 year old and his parents for an elective surgery.

PMID- 15502528
TI  - "Not listening, stubborn, and problems with sleeping"-interpreting a parent's
      concerns at a 3 year old's health supervision visit.

PMID- 15502529
TI  - International adoption: a four-year-old child with unusual behaviors adopted at
      six months of age.

PMID- 15502530
TI  - A child with a learning disability: navigating school-based services.

PMID- 15502531
TI  - Fatigue, decreased interest in play, motor delay, and elevated liver function
      tests in a 4-year-old boy.

PMID- 15502532
TI  - Cultural and linguistic determinants in the diagnosis and management of
      development delay in a four year old.

PMID- 15502533
TI  - An 8-year-old boy with school difficulties and "odd behavior".

PMID- 15502534
TI  - ADHD: the diagnostic process from different perspectives.

PMID- 15502535
TI  - When Asperger's syndrome and a nonverbal learning disability look alike.

PMID- 15502536
TI  - A difficult adjustment to school: the importance of family constellation.

PMID- 15502537
TI  - Failure to thrive in a four-month-old nursing infant.

PMID- 15502538
TI  - A newborn infant with a disorder of sexual differentiation.

PMID- 15502539
TI  - Parent requests growth hormone for child with idiopathic short stature.

PMID- 15502540
TI  - Selective affective response to a parent in a 6-month-old infant.

PMID- 15502541
TI  - An opportunity for office-based research.

PMID- 15502542
TI  - Benefits of a doula present at the birth of a child.

PMID- 15502543
TI  - The difficult parent: a reflective pediatrician's response.

PMID- 15502544
TI  - Organic or psychosomatic? Facilitating inquiry with children and parents.

PMID- 15502546
TI  - Interactions of biomedical and environmental risk factors for cognitive
      development: a preliminary study of sickle cell disease.
AB  - Sickle cell disease (SCD) is associated with a number of biopsychosocial risk
      factors for cognitive development. Understanding how these risk factors may
      interact is important for developing interventions for cognitive functioning. The
      authors assessed the cognitive abilities of children with SCD (n = 50) and
      related their performance to anemia severity, socioeconomic status (SES), and
      their interaction. Demographically matched peers without SCD (n = 36) served as a
      comparison group. Four areas of cognitive weakness were identified among children
      with SCD: general cognitive ability, crystallized ability, short-term memory, and
      processing speed. Anemia severity predicted general cognitive ability,
      crystallized ability, and processing speed. Interactions between anemia severity
      and SES were found for general cognitive ability and short-term memory. Disease
      effects in SCD appear to vary depending on the child's level of
      socioenvironmental risk. Biomedical interventions to benefit cognitive
      functioning may have different effects depending on whether additional
      socioenvironmental risk factors are present.

PMID- 15502547
TI  - Latina mothers' stances on stimulant medication: complexity, conflict, and
      compromise.
AB  - This study was undertaken to understand and describe Latina mothers' cognitions
      and attitudes toward the use of medication for their young children's behavior
      problems under the premise that these factors are determinants of noncompliance
      and inadequate adherence to medication treatments. Quantitative and qualitative
      data were extracted from a multimethod study of professional help seeking.
      Participants were 62 mothers from Cuba, Puerto Rico, and the Dominican Republic.
      Findings indicated that mothers overwhelmingly preferred treatment options other
      than medication primarily because they understood medication to be addictive,
      dulling of cognitive processes, and inappropriate for behavior problems.
      Inadequate adherence was common and logically consistent with maternal
      cognitions. Maternal choices with respect to the use of medication were
      transactional and quite complex in nature and changed over time. The strongest
      agents in this process were schools and the mothers' immediate family.
      Implications for clinical practice are presented.

PMID- 15502548
TI  - Ethnic and regional differences in primary care visits for attention-deficit
      hyperactivity disorder.
AB  - The ethnic and regional differences in primary care visits for children regarding
      the frequency of attention-deficit hyperactivity disorder (ADHD) diagnoses,
      stimulant prescriptions, and other mental health diagnoses were examined. The
      authors analyzed 6 years (1995-2000) of data from the National Ambulatory Medical
      Care Survey and the National Hospital Ambulatory Medical Care Survey and found
      that an ADHD diagnosis and/or a stimulant prescription were less likely to be
      recorded during visits by Hispanic-American youths relative to visits by white
      American youths. The authors also found that stimulant prescriptions were given
      more frequently for visits of children with ADHD in the south and west than in
      the northeast. Finally, no ethnic differences were found in the likelihood of
      receiving a psychotropic medication once an ADHD diagnosis was given or receiving
      a mental health diagnosis other than ADHD. Ethnic disparities in primary mental
      health care appear to exist for ADHD and not for other mental disorders pooled
      together.

PMID- 15502549
TI  - Can neurobehavioral examination predict the presence of cerebral injury in the
      very low birth weight infant?
AB  - This study examined in a regional cohort of 66 term age very low birth weight
      infants, the relationship between qualitative magnetic resonance imaging (MRI)
      measures of cerebral white and gray matter abnormalities and infant
      neurobehavioral functioning assessed by structured neurological examination. The
      diagnostic utility of the Dubowitz neonatal neurological examination in
      identifying children with severe cerebral abnormalities was also evaluated.
      Examination results revealed the presence of high rates of neurological
      abnormality, with 60% of infants scoring in the suboptimal range relative to
      infants born full term. Linear associations were found between the severity of
      structural cerebral abnormality on MRI and the quality of clinically rated infant
      neurobehavioral functioning, with increasing abnormalities being significantly
      associated with poorer neurological functioning. In particular, white matter
      abnormalities were significantly associated with lower mean tone and tone pattern
      scores and a tendency toward lower mean reflex scores. Gray matter abnormalities
      were significantly associated with lower tone and tone pattern scores and a
      tendency toward lower spontaneous movements and orientation/behavior scores.
      Finally, the Dubowitz Neonatal Neurological Examination was found to have
      relatively good sensitivity (88%; negative predictive value, 92%) but poor
      specificity (46%; positive predictive value, 34%) for identifying children with
      significant MRI abnormalities. Implications of these findings for the
      neurological evaluation of the very low birth weight infant are discussed.

PMID- 15502550
TI  - Family functioning in young children with cystic fibrosis: observations of
      interactions at mealtime.
AB  - This study examined family functioning at mealtime, a context relevant to the
      management of cystic fibrosis (CF). Thirty-three families of children with CF and
      a control sample of 33 families of children without a chronic illness were
      assessed. Family functioning was rated during a videotaped dinner using the
      McMaster Mealtime Interaction Coding System (MICS), and mealtime behavioral
      problems were assessed using the Behavioral Pediatrics Feeding Assessment Scale
      (BPFAS). Ratings for families of children with CF were lower than for control
      families on overall functioning and five of six MICS dimensions (Communication,
      Interpersonal Involvement, Behavior Control, Affect Management, Roles). In
      families of children with CF, better family functioning was related to less
      frequently occurring mealtime behavioral problems (BPFAS); however, family
      functioning was not related to the child's weight status or the child's caloric
      intake. Data support that nutritional intervention may be maximized if dietary
      adherence is promoted in the context of positive parent-child and family
      interactions.

PMID- 15502551
TI  - Bullying: concealed by behavioral and somatic symptoms.

PMID- 15502552
TI  - Pediatric interventions to support reading aloud: how good is the evidence?
AB  - Pediatricians and family practitioners increasingly provide free picture books
      and anticipatory guidance about reading aloud as part of routine health
      supervision for infants and young children, and arrange for volunteers to read
      aloud to children in the waiting rooms. These interventions comprise the Reach
      Out and Read (ROR) model, which has been adopted by more than 2000 clinical sites
      nationally. To date, 12 published studies have evaluated ROR and its variations,
      including three prospective, controlled trials. All but one have shown
      associations between ROR and increased reading aloud; additionally, four studies
      have linked program exposure to clinically meaningful increases in child
      language. Nonetheless, conclusive evidence of efficacy is lacking. This article
      provides a systematic, critical review of the literature, focusing on theoretical
      assumptions, issues of study design and measurement, and directions for future
      research.

PMID- 15502555
TI  - Flexible titanium nailing for the treatment of the unstable pediatric tibial
      fracture.
AB  - Tibia fractures in the skeletally immature patient can usually be treated without
      surgery. The purpose of this study was to assess the use of flexible titanium
      nails in the tibia that requires operative stabilization. Over a 5-year period,
      16 unstable tibia fractures in 14 patients were treated with flexible titanium
      intramedullary nails. All charts and radiographs were reviewed. The average age
      was 10 years 4 months. There were three open fractures. All fractures healed.
      Closed injuries obtained union by an average of 8 weeks, open fractures by an
      average of 15 weeks. There were no malunions. The average follow-up was 1 year 5
      months. There were no instances of growth arrest, remanipulations, or refracture.
      In the unstable pediatric tibia fracture, flexible titanium nails are an
      effective treatment to obtain and maintain alignment and stability.

PMID- 15502556
TI  - Complications and timing of follow-up after closed reduction and percutaneous
      pinning of supracondylar humerus fractures: follow-up after percutaneous pinning
      of supracondylar humerus fractures.
AB  - The purpose of this study was to evaluate the need for clinical evaluation with
      radiographs within 10 days of closed reduction and percutaneous pinning for the
      treatment of displaced supracondylar humerus fractures. Between May 1 and
      December 31, 2001, the authors evaluated the complications with closed reduction
      and percutaneous pinning of 104 displaced supracondylar humerus fractures. Fifty
      two of the patients had the initial follow-up examination with radiographs 10
      days or less after pinning; the other 52 patients had the initial follow-up
      examination with radiographs either after 10 days or on the day of pin removal.
      The overall complication rate for the series was 7.7% (8/104). All eight
      complications were in type III fractures. The early follow-up group had six
      complications; the late follow-up group had two complications. Baumann's angle,
      lateral humerocapitellar angle, and lateral rotational percentage were not
      significantly different between the two groups. The only variable tested that was
      associated with a complication was pin configuration. No association between late
      follow-up and complications was identified. The authors conclude that clinical
      and radiographic evaluation of routine displaced supracondylar humerus fractures
      requiring closed reduction and percutaneous pinning may be safely delayed until
      pin removal.

PMID- 15502557
TI  - The Bryan-Morrey triceps-sparing approach to open reduction of T-condylar humeral
      fractures in adolescents: cybex evaluation of triceps function and elbow motion.
AB  - Nine patients who underwent open reduction of a T-condylar distal humerus
      fracture through a Bryan-Morrey triceps-sparing approach were evaluated for
      triceps function and elbow motion. The average follow-up was 3 years 5 months.
      The average range of motion was -8 degrees to 136 degrees. Measured by Cybex
      testing, the average triceps deficit compared with the uninvolved arm was 6% at
      60 degrees/sec, 7% at 120 degrees/sec, and 10% at 180 degrees/sec. Compared with
      another study that tested triceps function after open reduction with the Campbell
      triceps-splitting approach, no statistically significant difference in function
      or range of motion was found. In this small series, early postoperative
      continuous passive motion was found to significantly increase range of motion.
      The Bryan-Morrey triceps-sparing approach can be used in children and adolescents
      who require open reduction for T-condylar distal humeral fractures.

PMID- 15502558
TI  - Osteogenesis imperfecta presenting as simultaneous bilateral tibial tubercle
      avulsion fractures in a child: a case report.
AB  - This is a case report of a unique presentation of a mild form of osteogenesis
      imperfecta (OI) (type IA) in a 9-year-old African-American boy who presented with
      simultaneous bilateral tibial tubercle avulsion fractures. The boy presented to
      the authors' emergency room complaining of acute bilateral knee pain. He could
      not perform a straight leg raise. Other than his orthopaedic examination,
      significant findings included blue sclera and irregular teeth. Radiographs and
      magnetic resonance imaging (MRI) confirmed bilateral tibia tubercle avulsion
      fractures. The patient underwent open reduction and internal fixation of his
      fractures, and postoperative genetic testing confirmed that the patient was
      heterozygous for OI. The authors present the fourth reported case of simultaneous
      bilateral tibial tubercle fractures. To their knowledge this is the first case of
      OI presenting with these fractures, the youngest reported case, and the first
      case with MRI documentation.

PMID- 15502559
TI  - Anterior cruciate ligament injury in pediatric and adolescent soccer players: an
      analysis of insurance data.
AB  - Injury claims from an insurance company specializing in soccer coverage were
      reviewed for a 5-year period. A total of 8215 injury claims (3340 females, 4875
      males) were divided into three categories: (1) all injury, (2) knee injury, and
      (3) ACL injury. Knee injuries accounted for 22% of all injuries (30% female, 16%
      male). ACL injury claims represented 31% of total knee injury claims (37% female,
      24% males). The youngest ACL injury was age 5. The ratio of knee injury/all
      injury increased with age. Compared with males, females demonstrated a higher
      ratio of knee injury/all injury and a higher ratio of ACL injury/all injury. This
      study demonstrates that ACL injury occurs in skeletally immature soccer players
      and that females appear to have an increased risk of ACL injury and knee injury
      compared with males, even in the skeletally immature. Future research related to
      ACL injury in females will need to consider skeletally immature patients.

PMID- 15502560
TI  - Results of zone II flexor tendon repair in children younger than age 6 years:
      botulinum toxin type A administration eased cooperation during the rehabilitation
      and improved outcome.
AB  - The inability of young children with a zone II flexor tendon repair to cooperate
      in postoperative care and rehabilitation may represent a high risk for medical
      and surgical complications. To forestall that risk, botulinum toxin type A (2.5
      U/kg, 7 U/kg) injection was used during surgery to induce forearm flexor muscle
      relaxation in seven children under 6 years old with zone 2 flexor tendon repairs.
      Patients received a controlled passive motion regimen after surgery. Results were
      evaluated on the basis of the acquisition of muscle tone and active finger
      movements, total range of motion of affected joints, postoperative grip strength,
      muscle atrophy, and phalangeal length. In this prospective clinical study, the
      mean follow-up was 18 months. All the children had good and excellent results
      based on the Strickland criteria. As for postoperative complications, one patient
      had bowstring and another had poor finger sensibility and first web space
      contracture that required Z-plasty. The selective use of botulinum toxin type A
      to weaken the targeted muscles generated a sufficient reduction in spontaneous
      activity of the fingers, permitting an improved rehabilitation program. Botulinum
      toxin type A administration could be an effective form of therapy, serving as an
      alternative or adjunct to conventional rehabilitation modalities in these
      children.

PMID- 15502561
TI  - The locked flexible intramedullary humerus nail in pediatric femur and tibia
      shaft fractures: a feasibility study.
AB  - There are several options for the treatment of long bone fractures in skeletally
      immature patients. Surgeon experience, type of fracture, and the possibility of
      damage to the physeal area dictate individual fracture management patterns.
      Notably, nail devices have not gained popularity in this patient group.
      Intramedullary locking nails have become the standard of care in adult patients
      due to decreased morbidity and mortality. A novel nail has been developed for
      humeral shaft fractures that uses a lateral starting position to avoid damage to
      the rotator cuff in humeral fracture fixation. This is possible because of the
      nail's transient flexibility during insertion. This study illustrates that it is
      feasible to insert this type of nail through multiple entry portals for both
      tibial and femoral fracture fixation, without damaging the physeal blood supply
      or growth areas.

PMID- 15502562
TI  - Biomechanical comparison of stainless steel and titanium nails for fixation of
      simulated femoral fractures.
AB  - Flexible intramedullary nails are commonly used to treat femoral fractures in
      children. This study evaluated the biomechanical differences between stainless
      steel and titanium nails when securing transverse and comminuted fractures in a
      synthetic femur model. Retrograde flexible stainless steel and titanium nails
      placed in a divergent "C" pattern were mechanically tested, and axial rotation
      and compression stiffness were analyzed with a two-way ANOVA. Rotational
      stability was significantly greater for titanium nails than stainless steel nails
      for both fracture patterns. Axial compression stiffness was significantly greater
      for titanium nails than stainless steel nails for both fracture patterns. There
      was no statistical difference between materials for axial "failure" load that
      produced 5 mm of shortening. Titanium intramedullary nails were more stable than
      stainless steel nails in torsion and axial compression. Both materials stabilized
      simulated fractures at levels beyond physiologic non-weight-bearing loads without
      permanent deformation.

PMID- 15502563
TI  - Comparison of radiolucent and fracture tables in the treatment of slipped capital
      femoral epiphysis.
AB  - A retrospective study was undertaken to see whether there was any difference in
      the time required and the accuracy of pin placement between slips pinned on a
      fracture table and those pinned on a radiolucent table. All patients were treated
      by single screw fixation of stable slipped capital femoral epiphysis (SCFE), 36
      on a fracture table and 29 on a radiolucent table. Mean operating room time on
      the fracture table (63 minutes) was greater than that on the radiolucent table
      (51.2 minutes) (P <0.05). Mean surgery time for the fracture table (38.55
      minutes) was greater than that on the radiolucent table (24.8 minutes) (P <0.05).
      The deviation of screw placement from the ideal for the two tables was not
      significantly different in the anteroposterior or lateral planes. The use of the
      radiolucent table, with manipulation of the limb to obtain lateral images of the
      hip, is a useful alternative to use of the fracture table for pinning of SCFE.

PMID- 15502564
TI  - The effects of subluxation of the femoral head with avascular necrosis in growing
      rabbits.
AB  - To validate the adverse effects of subluxation of the femoral head in Legg-Calve
      Perthes disease, the authors made an experimental model of Perthes disease with
      subluxation in growing rabbits by interrupting the epiphyseal artery
      (devascularization) and immobilizing the knee in extension (immobilization).
      Seventy-two rabbits, 4 to 5 weeks old, were divided into three groups: group A
      with both devascularization and immobilization (25 rabbits), group B with
      devascularization only (25 rabbits), and group C with immobilization only (22
      rabbits). In each experimental group, four to six rabbits each were killed at 1,
      2, 4, 8, and 12 weeks. After reviewing the serial radiographs and gross
      specimens, the authors found six radiologic and six macroscopic abnormalities.
      The incidence and the severity of deformity in group A rabbits were higher than
      that of groups B or C in terms of the overall incidence of deformities (P
      <0.001), head deformity scores (P <0.001), and the incidence of a total collapse
      of the capital femoral epiphysis. In conclusion, subluxation of the immature
      femoral head with avascular necrosis in rabbits increased femoral head
      deformities.

PMID- 15502565
TI  - The accuracy and reliability of estimation of lateral pillar height in
      determining the herring grade in Legg-Calve-Perthes disease.
AB  - The amount of the preserved lateral pillar height (LPH) for assigning Herring
      grades is estimated during daily practice in Perthes disease. Despite this
      estimation, Herring classification has been reported to have a good interobserver
      agreement. The purpose of this study was to investigate whether the amount of
      preserved LPH has an effect on interobserver agreement. The results of surgeons'
      estimates were compared with objective measurement results. Good agreement was
      found among three experienced pediatric orthopaedic surgeons in 50 patients (1
      vs. 2, kappa=0.527; 2 vs. 3, kappa=0.526; 1 vs. 3, kappa=0.539). Twenty of these
      cases had a ratio of the LPH scattered between 0.45 and 0.60 and 0.90 and 0.99
      (transition between group B and C, and group A and B). When the borderline cases
      were evaluated separately, the interobserver reliability was poor (1 vs. 2,
      kappa=0.194; 2 vs. 3, kappa=0.256; 1 vs. 3, kappa=0.154), which may be explained
      by misperception of the preserved LPH. If the Herring classification is to be
      used as the prognostic indicator for deciding among the treatment alternatives,
      and LPH is the major determinant of the management, measurements should be used
      instead of estimates, especially in borderline cases.

PMID- 15502566
TI  - Remodeling of the proximal femur after upper femoral varus osteotomy for the
      treatment of Legg-Calve-Perthes disease.
AB  - Upper femoral varus osteotomy of the proximal femur without rotation has been the
      surgical treatment of choice by the senior author (D.S.W.) in 124 cases of Legg
      Calve-Perthes disease. There have been no previous studies documenting the nature
      of the remodeling process after this surgical procedure. The authors analyzed the
      radiographic changes that occur over time at the osteotomy site and the angle of
      inclination (neck-shaft angle). Inclusion criteria were a minimum of 2 years of
      radiographic follow-up. Patient follow-up ranged from 2 to 7 years (average 5.3
      years). Goniometric measurements were performed at the osteotomy site as well as
      on the neck-shaft angle on preoperative, postoperative, and yearly AP
      radiographs. Results were recorded with reference to the percentage of correction
      per year. The authors also compared the results of patients younger than 8 years
      of age (group 1) with those older than 8 years of age (group 2). The average
      percentage of remodeling at the osteotomy site was 60% at 6 years, with 40% of
      the correction occurring within the first 2 years. The neck-shaft angle remodeled
      in a similar fashion: there was approximately two-thirds correction by 7 years,
      with most correction being evidenced within 3 to 4 years. There was no
      significant difference in remodeling based on the age of the patient at
      presentation. In conclusion, radiographically significant remodeling is to be
      expected after femoral varus osteotomy despite the diseased proximal femoral
      epiphysis.

PMID- 15502567
TI  - Convex growth arrest in the treatment of congenital spinal deformities,
      revisited.
AB  - The authors studied 32 patients to delineate the reliability of well-defined but
      frequently extended indications to define the ideal patient who will benefit from
      convex growth arrest. Mean age at the time of convex growth arrest was 29 (range
      6-72) months, and average follow-up was 40 (24-120) months. Mean Cobb angle was
      55 degrees (31-105 degrees) before surgery and 50 degrees (13-107 degrees) at
      final follow-up. Thirteen patients (41%) had a true epiphysiodesis effect, while
      15 (47%) had fusion and 4 (12%) had progression. The age at surgery, magnitude,
      length and location of the curve, presence of intraspinal anomaly, and presence
      of sagittal plane or rib deformity were investigated in terms of the outcome, but
      none of these parameters was found to have an effect on the outcome. In
      conclusion, convex growth arrest is a safe and effective method in the management
      of the young patients with congenital spinal deformities. It can be performed for
      the balanced and cosmetically acceptable deformities of patients younger than 5
      years of age regardless of the type, length, magnitude, and location of the
      curve, the existence of associated rib fusion, or the presence of sagittal plane
      abnormality.

PMID- 15502568
TI  - Effectiveness of spinal release and halo-femoral traction in the management of
      severe spinal deformity.
AB  - The purpose of this retrospective review was to assess the effectiveness of
      spinal release and halo-femoral traction in the management of severe spinal
      deformity. Twenty-four patients had halo-femoral traction and a spinal release.
      Analysis focused on pre-traction curve, preoperative curve in bending or
      hyperextension films, final traction curve, traction weight as a percent of body
      weight, and complications associated with traction. The average pre-traction
      curve was 95 degrees and the average pre-traction curve in bending was 73
      degrees; the final traction average curve was 44 degrees. The difference between
      the magnitude of curve correction in bending and traction films was statistically
      significant. Traction weight was increased to an average of 54% of body weight.
      The only complication was a bilateral lower extremity sensory deficit that
      resolved after traction weight reduction. The average final correction was 71%.
      Spinal release and halo-femoral traction offer a safe approach to the correction
      of severe spinal deformities before fusion.

PMID- 15502569
TI  - Congenital scoliosis and vertebral malformations: characterization of segmental
      defects for genetic analysis.
AB  - The developmental and genetic etiology of most congenital vertebral malformation
      disorders remains unknown. The objective of this study was to evaluate and
      classify congenital vertebral defect cases into groupings based on developmental
      etiology for clinical genetic studies. This classification is intended to be
      distinct from but complementary to traditional groupings based on spinal
      curvature or progression. In the first step of this analysis, the authors
      identified 84 cases of vertebral segmentation disorders by radiologic screening
      and prospectively recruited 39 of these patients into a clinical genetic study.
      Next, the authors quantified the extent of contiguous defects and organized cases
      by craniocaudal localization. Finally, the authors used available clinical
      association data to identify syndromic and nonsyndromic subcategories, and
      identified a high rate of orthopaedic and neurologic associations in nonsyndromic
      patients. This type of analysis has identified subgroups of patients with
      multiple, contiguous segmental defects and orthopaedic associations that are
      particularly suitable for further genetic analysis.

PMID- 15502570
TI  - Treatment of congenital muscular torticollis in patients older than 8 years.
AB  - The authors treated congenital muscular torticollis by sternocleidomastoid muscle
      release in 32 patients over 8 years of age who had not received any prior medical
      treatment or in whom torticollis had recurred since initial treatment. The
      results were analyzed to compare clinical results after an average of 39 months
      (range 24-74 months) by dividing the patients into two groups: patients who were
      still in the growing period (group 1, n=19) and patients who had finished growth
      (group 2, n = 13) at surgery. According to the total score table by Cheng et al
      (which includes motion deficits, craniofacial asymmetry, scar, band, head tilt,
      and subjective assessment), there were 13 excellent and 6 good results in group 1
      and 2 excellent, 8 good, and 3 fair results in group 2. The clinical results were
      statistically less successful in group 2 than in group 1 by Cheng's score table
      (P <0.05). However, most patients showed marked improvement in neck motion and
      head tilt, with satisfactory functional and cosmetic results. Thus, in patients
      older than school age, even for those who have finished growth, sufficient
      unipolar or bipolar release of the sternocleidomastoid muscle and intensive
      postoperative care are expected to yield satisfactory treatment results.

PMID- 15502571
TI  - Functional analysis of upper limb deformities in osteogenesis imperfecta.
AB  - The charts and radiographs of 159 children with osteogenesis imperfecta (OI) were
      retrospectively reviewed to measure the severity of upper limb deformities and to
      evaluate the functional outcome using the Pediatric Evaluation of Disability
      Inventory (PEDI). The patients were classified according to the Sillence
      classification modified by Glorieux: 51 type 1, 33 type 3, 54 type 4, and 21 5ype
      5. Fifty-nine patients (37.1%) had deformities of their upper limbs. Children
      with type 3 OI had the highest incidence and the most severe deformities. The
      humerus was the most commonly involved bone, followed by the ulna and radius.
      Upper limb deformities were classified into four groups according to the severity
      of the maximum deformity angle. The mean self-care scores of PEDI were
      significantly low only in the group with severe deformities, but mobility scores
      were dramatically decreased in both the moderate and severe deformity groups.
      Therefore, upper limb deformities in children with OI do not represent only a
      cosmetic problem, but may also significantly impair functional activities of
      daily living.

PMID- 15502572
TI  - Kinematic assessment of the upper extremity in brachial plexus birth palsy.
AB  - Children with brachial plexus birth palsy (BPBP) may have shoulder external
      rotation and abduction weakness that can restrict activities of daily living
      (ADLs). Static range of motion measurements may not measure ADL restrictions.
      Motion analysis has been used to quantify gait limitations and measure changes
      associated with treatment. The purpose of this study was to determine whether
      upper extremity motion analysis (UEMA) can measure the differences in shoulder
      motion during ADLs between children with BPBP and normal children. Following a
      previously described UEMA protocol, 55 children with BPBP and 51 normal children
      (control group) were studied. Kinematic data of selected ADLs were collected
      before surgery. UEMA was used to measure statistically significant differences
      between children with BPBP and control subjects for all planes of shoulder motion
      in all activities tested. The authors conclude that UEMA can discriminate between
      children with BPBP and control subjects during selected ADLs, and suggest that
      UEMA can also be used to measure the effects of surgical interventions in
      children with BPBP.

PMID- 15502573
TI  - Focal fibrocartilaginous dysplasia in the upper limb: seven additional cases.
AB  - Focal fibrocartilaginous dysplasia is a benign bone lesion known to cause
      deformity around the knee in young children. Three cases affecting the long bones
      of the upper limb have been reported, and little is known of the natural history.
      This study reports seven more cases affecting the upper extremity. All patients
      presented with deformity in early childhood. The location was the radius in two,
      the ulna in three, the proximal phalanx in one, and the middle phalanx in one.
      The radiographic appearance of the condition is diagnostic, regardless of the
      bone it affects. Proportional shortening of the affected segment was present in
      all patients. The phalangeal cases had marked deformity and were osteotomized,
      with early recurrence of the deformity in one case. The forearm lesions did not
      all resolve spontaneously. In the two patients with 7-year follow-up, the length
      discrepancy increased from 0.5 cm to 2 cm and a degree of cosmetic deformity
      remained, without functional impairment. Ulna lesions place the radiocapitellar
      joint at risk for dislocation and should be observed for this complication.

PMID- 15502574
TI  - Analysis of scar formation after lower limb lengthening: influence on cosmesis
      and patient satisfaction.
AB  - Limb lengthening aims to reduce limb length discrepancy, improve cosmesis, and
      permit more functional mobility. Scarring, however, is a major concern of
      patients. In this study 25 patients (27 lengthening sites) were assessed; 6 sites
      were lengthened with Orthofix and 21 sites with Ilizarov. Altogether, 452 pin
      tract scars were assessed. The mean scar length was 11.5 mm in the Ilizarov group
      (n=415) and 54.1 mm in the Orthofix group (n=37). The mean scar width was 5.6 mm
      in the Ilizarov group and 11.5 mm in the Orthofix group. The mean patient
      satisfaction was 7.3 in the Orthofix group and 5.5 in the Ilizarov group. The
      mean Vancouver score was 0.66 in the Ilizarov group and 3.1 in the Orthofix
      group. The scars were shorter and cosmetically better in the Ilizarov group, but
      patients were more satisfied in the Orthofix group because there were fewer
      scars. Patients were also more satisfied with the thigh scars than with the leg
      scars because clothing can easily cover the thigh scars.

PMID- 15502575
TI  - Complications of distraction osteogenesis in short first metatarsals.
AB  - The authors analyzed the results and complications of metatarsal lengthening in
      short first metatarsals by distraction osteogenesis. There were 13 first
      metatarsal lengthenings in eight patients. Mean age was 18.8 years and the
      average percentage of lengthening was 49.2%. The average healing index was 72.4
      days/cm. The major complication was cavus foot, which was noticed in four feet.
      All great toes showed some loss of motion at metatarsophalangeal (MP) joint.
      Other complications were hallux valgus, angulation of the metatarsals, and pin
      tract infection each in two feet. The functional score according to the American
      Orthopedic Foot and Ankle Society (AOFAS) hallux MP joint, interphalangeal joint
      scale was excellent in 11 and good in 2. All patients were satisfied with the
      procedure. To avoid potential complications such as MP joint subluxation, cavus
      foot, and hallux valgus, the first metatarsal lengthening should not exceed 50%
      of the original length.

PMID- 15502576
TI  - Early graft failure in lateral column lengthening.
AB  - One hundred thirty feet in 96 children (47 girls, 49 boys) treated with lateral
      column lengthening to correct planovalgus foot deformities were retrospectively
      reviewed. Sixty-nine feet had lengthening through the neck of the calcaneus (39
      allografts, 30 autografts) and 61 feet had calcaneocuboid joint lengthening and
      arthrodesis (58 allografts, 3 autografts). Radiographic evaluation before
      surgery, after surgery, and at follow-up was used to determine loss of
      correction, graft lucencies or fragmentation, and apparent loss of graft length.
      Collapse (loss of correction with concomitant loss of graft length) was observed
      between 0.3 and 1.3 years after surgery. Seventeen (29.3%) of the 58
      calcaneocuboid joint allografts demonstrated collapse. None of the 69
      intracalcaneal grafts (39 allografts, 30 autografts) and none of the 3
      calcaneocuboid autografts collapsed. This series suggests that lateral column
      lengthening through the neck of the calcaneus may provide a more durable
      correction than lengthening with calcaneocuboid joint fusion.

PMID- 15502577
TI  - Percutaneous epiphysiodesis using transphyseal screws (PETS): prospective case
      study and review.
AB  - Percutaneous epiphysiodesis using transphyseal screws (PETS) is a relatively new
      procedure being used for the correction of moderate leg length discrepancy and
      angular deformities in children. Over a mean follow-up of 2.4 years the authors
      followed prospectively 18 patients who underwent PETS. Nine had correction of
      angular deformity and nine had leg length inequality. The average reduction in
      leg length discrepancy was from 3.33 to 1.36 cm. The average improvement in
      angular deformity was 69%. This quick, minimally invasive, and potentially
      reversible procedure has the added benefits of a short hospital stay with low
      morbidity, making it a suitable alternative to the more traditional methods of
      epiphysiodesis.

PMID- 15502578
TI  - Growing pains: are they due to increased growth during recumbency as documented
      in a lamb model?
AB  - The rate and patterns of longitudinal bone growth are affected by many different
      local and systemic factors; however, uncompromised growth is usually considered
      to be smoothly continuous, with predictable accelerations and decelerations over
      periods of months to years. The authors used implanted microtransducers to
      document bone growth in immature lambs. Bone length measurements were sampled
      every 167 seconds for 21 to 25 days. The authors show that at least 90% of bone
      elongation occurs during recumbency and almost no growth occurs during standing
      or locomotion. The authors hypothesize that growth may also occur in children
      during rest or sleep, thus supporting the concept of nocturnal growth and perhaps
      a relationship to growing pains.

PMID- 15502579
TI  - The multiplier method for prediction of adult height.
AB  - The authors propose the "height multiplier method," a new, simple, universal
      method to predict adult height. The authors calculated age- and gender-specific
      height multiplier values and validated their use for height prediction. Average
      height multiplier values (M) for boys and girls were calculated by dividing
      height at skeletal maturity (Htm) by present height (Ht) for each age, gender,
      and height percentile (M=Htm/Ht) using data published by the Centers for Disease
      Control and Prevention (CDC). The accuracy of the multiplier method was compared
      with the CDC growth charts using longitudinal growth data from 52 normal
      children. No significant differences were noted between predictions made using
      the CDC growth charts versus the multiplier method. The authors also compared the
      CDC-derived multiplier values with other growth databases from around the world
      and from different eras. Height multipliers were independent of height
      percentile, race, and generation, indicating that the multiplier method is
      universal.

PMID- 15502580
TI  - Incidence of inpatient surgeries in children and young adults with childhood
      orthopaedic diagnoses.
AB  - The incidence of orthopaedic surgery for young people with childhood onset of
      orthopaedic disabilities is not well documented. This study tabulated that
      incidence in the past two decades in California. Trauma, tumors, and hand surgery
      were not included in the study. Common pediatric orthopaedic diagnoses by ICD-9
      code requiring CPT orthopaedic surgical procedures were tabulated in three years:
      1983, 1990, and 1999. The most common procedures in each of these years studied
      were, in order of incidence, scoliosis, congenital hip problems, slipped femoral
      capital epiphyses, and clubfeet. The incidence of surgery for scoliosis and
      slipped femoral capital epiphyses increased over the past two decades. These data
      should be helpful in planning for future inpatient services for orthopaedically
      handicapped children.

PMID- 15502581
TI  - Anesthetic considerations for fracture management in the outpatient setting.

PMID- 15502582
TI  - Use and abuse of knee MRI in assessment of pediatric knee intraarticular
      disorders.

PMID- 15502583
TI  - Looking forward, looking back: a celebration.

PMID- 15502584
TI  - Childhood reactions to terrorism.

PMID- 15502586
TI  - Psychotropic medication use in high-risk youths.

PMID- 15502587
TI  - Seclusion and restraint "one-hour rule".

PMID- 15502588
TI  - Clonidine for self-injurious behavior.

PMID- 15502589
TI  - Antimyocardial antibodies in anorexia nervosa.

PMID- 15502590
TI  - Pathological gambling and substance use.

PMID- 15502591
TI  - The role of parental burden in child mental health service use: longitudinal
      study.
AB  - OBJECTIVE: To examine the relative contributions of symptom severity, functional
      impairment, and parental burden in predicting the use of specialist child mental
      health services over a 4-year period. METHOD: Between 1999 and 2000, parental
      Strengths and Difficulties Questionnaires were completed on a community-based
      sample of 1,168 (40% response rate) 5- to 11-year-olds in the United Kingdom.
      Using a prospective longitudinal design, these data were related to subsequent
      referral records (until 2003). Children who were and were not referred to
      specialist mental health services were compared. Changes in the association
      between predictor variables (symptoms, impairment, and burden) and referral over
      time were also examined. RESULTS: Over 4 years, 5.1% of children were referred.
      After controlling for all other predictors, only severity of symptoms predicted
      future referrals (for each 1-point increase on the total symptoms score, odds
      ratio 1.15; 95% confidence interval=1.09-1.21). Burden was only associated with
      referrals made during the first year, whereas conduct and emotional problems
      predicted subsequent referrals. CONCLUSIONS: In contrast to cross-sectional
      studies that have highlighted the roles of functional impairment and parental
      burden in predicting specialist service use, this longitudinal study indicates
      that symptom severity best predicts future referrals. For children with mental
      health problems, there is considerable delay in accessing specialist services.

PMID- 15502592
TI  - The services for children and adolescents-parent interview: development and
      performance characteristics.
AB  - OBJECTIVE: To date, no instrument has been developed that captures children's
      services use across primary care, specialty mental health, and other settings,
      including setting, treatment type, provider discipline, and length and intensity
      of specific interventions over varying follow-up periods. The authors developed a
      highly structured services assessment measure [Services for Children and
      Adolescents-Parent Interview (SCAPI)] for use in the National Institute of Mental
      Health Multimodal Treatment Study of Children With Attention Deficit
      Hyperactivity Disorder (MTA). METHOD: After successfully piloting and refining
      the SCAPI during initial phases of the MTA, the authors used this measure at 24
      months post-randomization to ascertain the previous 6 months of services use for
      all participating (516 of 579) MTA children and families and 285 age- and gender
      matched classroom control children. RESULTS: Findings revealed meaningful, face
      valid differences between MTA and control children in levels and types of
      services used during the previous 6-month period. Services use data reported by
      parents was substantially in accord with data independently gathered by the
      research data center. Site variations were found in the level and use of several
      specific services, such as individual child psychotherapy (sites ranged from 0%
      to 6.8% among classroom controls compared with 9.7% to 46.1% among MTA
      participants) and special education services (0% to 14.6% among classroom
      controls, 27.5% to 34.8% among MTA participants), consistent with differences
      reported in other studies. CONCLUSIONS: These data support the descriptive
      validity of SCAPI-ascertained services use data and indicate that the SCAPI can
      provide investigators and policymakers a valid means of assessing services type,
      intensity, onset and offset, provider type, and content.

PMID- 15502594
TI  - Use of health and school-based services in Australia by young people with
      attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: To examine use of health (including psychiatric) and school-based
      services by children and adolescents who met symptom criteria for attention
      deficit/hyperactivity disorder (ADHD), the factors associated with service use,
      and barriers to service access. METHOD: The relationship between parents'
      perceptions of children's need for professional help, the impact of children's
      problems on children and parents, and services used during the previous 6 months
      were examined in a national sample of 398 children and adolescents with ADHD
      symptoms aged 6 to 17 years (70% response rate). Information was obtained from
      parents who completed the Diagnostic Interview Schedule for Children Version IV
      and standard questionnaires. Data collection took place between February and May
      1998. RESULTS: Only 28% of those with ADHD symptomatology had attended health or
      school-based services. Among these, 41% had attended both health and school-based
      services, 39% had attended only health services, and 20% had attended only school
      based services. Sixty-nine percent of parents attending health services wanted
      additional help. Parental perceptions that children needed professional help,
      children's functional impairment, the impact of problems on parents, and comorbid
      depressive or conduct disorders had a significant and independent relationship
      with service use. CONCLUSIONS: A minority of children and adolescents with ADHD
      symptomatology receives professional help for their problems in Australia.
      Counseling is the most frequent help provided, with many parents wanting
      additional help beyond that already provided. Factors other than children's ADHD
      symptomatology have a significant relationship with service attendance. Practical
      issues, including the cost of services and waiting lists are the most common
      barriers cited by parents as hindering access to services.

PMID- 15502593
TI  - Reliability of the services for children and adolescents-parent interview.
AB  - OBJECTIVE: To describe the psychometric properties and test the reliability of a
      new instrument designed to measure mental health services use within pediatric
      clinical samples, the Services for Children and Adolescents-Parent Interview
      (SCAPI), which was developed by the National Institute of Mental Health
      Multimodal Treatment Study of Children With Attention Deficit Hyperactivity
      Disorder (MTA). METHOD: Similarities and differences with other measures of
      services use are described. Ten types of services are measured by the SCAPI.
      Formal test-retest reliability testing was carried out in 104 subjects with a
      mean time between tests of 18 days. RESULTS: Test-retest kappa values ranged from
      0.49 to 1.00, with an overall kappa value for all services of 0.97. Seven of the
      10 service types had kappa values of 0.75 or higher, indicating excellent
      reliability. In addition, matched responses on specific questions about reasons
      for seeking services, starting and ending dates, number and length of visits, and
      type of provider seen were more than 75% for most service categories,
      consistently so for reporting of medications and school services. CONCLUSIONS:
      The SCAPI is a reliable instrument for assessing mental health and related
      services use and may be an especially valuable adjunct in studies involving
      clinical samples, especially clinical trials.

PMID- 15502595
TI  - Screening for childhood anxiety symptoms in primary care: integrating child and
      parent reports.
AB  - OBJECTIVE: Parents' concerns typically determine the focus of a primary care
      visit. This study examined which information is lost if child reports are
      excluded from screening for anxiety. It also explores the use in primary care of
      the Screen for Child Anxiety Related Emotional Disorders (SCARED) and the
      Pediatric Symptom Checklist (PSC-17). METHOD: Two hundred thirty-six children (8
      12 years 11 months) and their parents completed SCARED and PSC-17 before a
      primary care visit occurring during discrete periods between June 1999 and March
      2001. RESULTS: Child reports yielded higher SCARED scores than parent reports
      (mean=18.12, SD=12.14 versus 14.43, SD=10.34, p <.001). Somatic/panic and
      separation anxiety accounted for 73.8% of the excess score from children's
      reports. The level of parent-reported symptoms did not vary with demographics.
      Female gender and younger age predicted greater excess reporting by children.
      Parent and child scores were moderately to highly correlated (R=0.55 total score;
      0.40-0.58 subfactors). CONCLUSIONS: There are discrete anxiety domains in which
      children's reports are likely to yield more information than that of parents.
      This phenomenon is almost entirely attributable to variations in the level of
      symptoms reported by children. Studies are needed to design brief screening
      procedures that integrate parent and child reports and carry age- and gender
      adjusted thresholds.

PMID- 15502596
TI  - Resilient children of injection drug users.
AB  - OBJECTIVE: To examine associations between resilience in children of injection
      drug users and children's coping strategies, parenting stress, and children's
      social support. METHOD: Injection drug-using parents (n=91) and their children
      aged 6 to 11 (n=117) were recruited in Baltimore (1997-1999). Resilience was
      defined as scoring in the lowest quartile of the Child Behavior Checklist total
      psychopathology score. Coping strategies used by resilient and nonresilient
      children, the extent and types of social support that they received, and the
      level of parenting stress reported by their parents were compared and contrasted.
      RESULTS: Rates of depressive, anxiety, and disruptive behavior disorders were
      15.4%, 22.2%, and 21.4%, respectively, for the entire sample. Compared with the
      nonresilient, resilient children were less likely to use two avoidance coping
      strategies (internalizing [p=.002] and externalizing [p=.017]). The level of
      actual support received by resilient and nonresilient children did not differ
      significantly (p=.202). Perceived support was greater among resilient children
      (as reported by their parents; p <.001), and their parents reported lower
      parenting stress (p=.042). CONCLUSIONS: A significant proportion of children of
      injection drug users are in need of clinical care. Interventions to help children
      of substance-abusing parents modify their coping style merit exploration.

PMID- 15502597
TI  - Risk of substance use disorders in adolescents with bipolar disorder.
AB  - OBJECTIVE: Previous work in adults and youths has suggested that juvenile onset
      bipolar disorder (BPD) is associated with an elevated risk of substance use
      disorders (SUD). Considering the public health importance of this issue, the
      authors now report on a controlled study of adolescents with and without BPD to
      evaluate the risk of SUD. METHOD: Probands with DSM-IV BPD (n=57, mean age +/-
      SD=13.3 +/- 2.4 years) and without DSM-IV BPD (n=46, 13.6 +/- 2.2 years) were
      studied. Structured psychiatric interviews and multiple measures of SUD were
      collected. RESULTS: Bipolar disorder was associated with a highly significant
      risk factor for SUD (32% versus 7%, Z=2.9, p=.004) that was not accounted for by
      conduct disorder (adjusted odds ratio=5.4, p=.018). Adolescent-onset BPD (> or
      =13 years) was associated with a higher risk of SUD compared with those with
      child-onset BPD (chi1=9.3, p=.002). CONCLUSIONS: These findings strongly indicate
      that BPD, especially adolescent onset, is a significant risk factor for SUD
      independently of conduct disorder.

PMID- 15502598
TI  - Paroxetine treatment in children and adolescents with obsessive-compulsive
      disorder: a randomized, multicenter, double-blind, placebo-controlled trial.
AB  - OBJECTIVE: To assess the efficacy and safety of paroxetine for the treatment of
      pediatric obsessive-compulsive disorder. METHOD: Children (7-11 years of age) and
      adolescents (12-17 years of age) meeting DSM-IV criteria for obsessive-compulsive
      disorder were randomized to paroxetine (10-50 mg/day) or placebo for 10 weeks.
      The primary efficacy measure was change from baseline in the Children's Yale
      Brown Obsessive-Compulsive Scale (CY-BOCS) total score at week 10 last
      observation carried forward end point. Safety was assessed primarily through
      adverse event monitoring. RESULTS: A total of 207 patients were randomized to
      treatment. Of these, 203 were included in the intention-to-treat population.
      Adjusted mean changes from baseline at week 10 observation carried forward end
      point in CY-BOCS total score for patients receiving paroxetine and placebo were 
      8.78 (SE=0.82) and -5.34 points (SE=0.77), respectively. The adjusted mean
      difference, -3.45 in favor of paroxetine, was statistically significant (95%
      confidence interval=-5.60 to -1.29, p=.002). Adverse events were generally mild
      to moderate in intensity. A total of 10.2% (10/98) of patients in the paroxetine
      group and 2.9% (3 of 105) in the placebo group discontinued treatment because of
      adverse events. CONCLUSIONS: Paroxetine is an effective and generally well
      tolerated treatment for obsessive-compulsive disorder in children and
      adolescents.

PMID- 15502599
TI  - Fluoxetine treatment for prevention of relapse of depression in children and
      adolescents: a double-blind, placebo-controlled study.
AB  - OBJECTIVE: To compare fluoxetine 20 to 60 mg/day with placebo for prevention of
      relapse of major depressive disorder in children and adolescents who had achieved
      Children's Depression Rating Scale, Revised scores of < or =28 during treatment
      with fluoxetine 20 to 60 mg. METHOD: In this 32-week relapse-prevention phase of
      a double-blind, multicenter, placebo-controlled 51-week study, 20 patients
      continued to receive their fixed dose of fluoxetine (F/F group), while 20 similar
      patients were switched to placebo (F/P group). Definition of relapse for the
      primary analysis was a Children's Depression Rating Scale, Revised score of >40
      with a 2-week history of clinical deterioration or relapse in the opinion of the
      physician. Adverse events were compared between treatment groups to assess
      discontinuation-emergent adverse events. RESULTS: Mean time to relapse was longer
      in the F/F recipients than in the F/P recipients (p=.046). Relapse occurred in an
      estimated 34% in the F/F cohort and 60% in the F/P cohort. Incidence of adverse
      events and tolerability were similar in the F/F and F/P groups, suggesting that
      fluoxetine is not associated with significant discontinuation events.
      CONCLUSIONS: Fluoxetine 20 to 60 mg/day was well tolerated and can significantly
      delay relapse of major depressive disorder symptoms in children and adolescents.

PMID- 15502600
TI  - A double-blind, placebo-controlled trial of dexmethylphenidate hydrochloride and
      d,l-threo-methylphenidate hydrochloride in children with attention
      deficit/hyperactivity disorder.
AB  - OBJECTIVE: To evaluate the efficacy and safety of dexmethylphenidate
      hydrochloride (d-MPH, Focalin) for the treatment of attention
      deficit/hyperactivity disorder (ADHD) and to test an a priori hypothesis that d
      MPH would have a longer duration of action than d,l-threo-methylphenidate (d,l
      MPH). METHOD: This was a randomized, double-blind study conducted at 12 U.S.
      centers. One hundred thirty-two subjects received d-MPH (n=44), d,l-MPH (n=46),
      or placebo (n=42) twice daily for 4 weeks, with titration of the dose based on
      weekly clinic visits. The primary efficacy variable was change from baseline to
      last study visit on teacher-completed Swanson, Nolan, and Pelham Rating Scale
      (Teacher SNAP). Secondary efficacy measures included the change on parent
      completed SNAP (Parent SNAP), Clinical Global Impressions Scale-Improvement (CGI
      I) score, and Math Test performance. Assessments at home in late afternoon were
      included to test the hypothesis that d-MPH would have a longer duration of
      efficacy than d,l-MPH. Safety was assessed through monitoring occurrence and
      severity of adverse events and discontinuations related to them. RESULTS:
      Treatment with either d-MPH (p=.0004) or d,l-MPH (p=.0042) significantly improved
      Teacher SNAP ratings compared with placebo. The d-MPH group showed significant
      improvements compared with placebo on the afternoon Parent SNAP ratings (p=.0003)
      and scores on the Math Test (p=.0236) obtained late in the afternoon at 6:00 p.m.
      Sixty-seven percent of patients showed improvement on d-MPH and 49% on d,l-MPH
      based on CGI-I scores. Both d-MPH and d,l-MPH were well tolerated, no patient in
      the d-MPH group and only two patients each in the d,l-MPH and placebo groups
      discontinued the study. CONCLUSIONS: For the treatment of ADHD, an average
      titrated dose of 18.25 mg/day of d-MPH is as efficacious and safe as an average
      titrated dose of 32.14 mg/day of d,l-MPH. Both active treatments have large
      effect sizes. Thus, d-MPH and d,l-MPH appear to provide similar efficacy, and d
      MPH may have longer duration of action after twice-daily dosing, but additional
      studies are needed to determine the statistical and clinical significance of this
      possibility.

PMID- 15502601
TI  - A post hoc analysis of d-threo-methylphenidate hydrochloride (focalin) versus d,l
      threo-methylphenidate hydrochloride (ritalin).
AB  - OBJECTIVE: To evaluate clinical measures of the benefit/risk ratio in a post hoc
      analysis of a clinical trial of d-threo-methylphenidate hydrochloride (d-MPH) and
      d,l-threo-methylphenidate hydrochloride (d,l-MPH). METHOD: Data from a phase III
      clinical trial was used to compare equimolar doses of d-MPH and d,l-MPH treatment
      for attention-deficit/hyperactivity disorder (ADHD) on clinician ratings of
      improvement/deterioration, teacher ratings of remission, and duration of action.
      RESULTS: d-MPH was clinically and statistically significantly superior to d,l-MPH
      on clinician's dimensional ratings of global improvement, teacher ratings of
      remission of ADHD symptoms and parent 6:00 p.m. ADHD symptom ratings. No
      treatment differences were observed for symptom ratings at 3:00 p.m. and for 6:00
      p.m. math test performance. CONCLUSION: The results suggest that the two drugs
      may have distinct profiles on the measures analyzed. Because d-MPH may have be
      more than twice the potency of d,l-MPH, the differences reported here are only
      applicable to the doses of the study drugs involved in the clinical trial. The
      results are limited by the exploratory nature of our analysis, small samples, and
      multiple analyses. The findings are suggestive that further study is warranted to
      look at these differences prospectively but cannot be used to draw clinical
      conclusions at this time.

PMID- 15502603
TI  - Event-related FMRI evidence of frontotemporal involvement in aberrant response
      inhibition and task switching in attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: Response inhibition deficits are characteristic of individuals with
      attention-deficit/hyperactivity disorder (ADHD). Previous functional magnetic
      resonance imaging (fMRI) studies investigating the neural correlates of this
      dysfunction have used block designs, making it difficult to disentangle
      activation differences specifically related to response inhibition from
      activation differences related to subprocesses involved in task performance. The
      current study was designed to further enhance our understanding of this critical
      function in individuals with ADHD using event-related fMRI. METHOD: Ten
      adolescent boys diagnosed with ADHD, combined type, and 12 typically developing
      controls completed a Go/NoGo task modified to control for novelty processing.
      RESULTS: The ADHD group made significantly more errors of omission and more
      errors of commission than the control group. Further, compared with controls,
      individuals with ADHD showed marked abnormalities in brain activation during
      response inhibition, including hypoactivation of the anterior/mid-cingulate
      cortex extending to the supplementary motor area and hyperactivation of the left
      temporal gyrus. CONCLUSIONS: The authors suggest that underactivation in frontal
      regions reflects core deficits in response/task-switching abilities for the ADHD
      group.

PMID- 15502602
TI  - Comparative pharmacodynamics and plasma concentrations of d-threo-methylphenidate
      hydrochloride after single doses of d-threo-methylphenidate hydrochloride and d,l
      threo-methylphenidate hydrochloride in a double-blind, placebo-controlled,
      crossover laboratory school study in children with attention
      deficit/hyperactivity disorder.
AB  - OBJECTIVE: Methylphenidate has four optical isomers due to two asymmetries
      (erythro-threo and dextro-levo). The initial commercial formulation eliminated
      the erythro isomer, but the dextro-levo asymmetry was racemic, with equal amounts
      of d and l-threo isomers (d,l-MPH). Previous work has suggested that the d-threo
      isomer methylphenidate (d-MPH) rather than the l-threo isomer (l-MPH) is
      responsible for the clinical effects in children with attention
      deficit/hyperactivity disorder (ADHD). This study compared the efficacy of acute
      equimolar doses of d-MPH and dl-MPH in reducing ADHD symptoms over an 8-hour
      period in a laboratory school setting and investigated the relationship of
      efficacy to plasma levels of MPH. METHOD: Thirty-two children with ADHD enrolled
      in this double-blind, placebo-controlled, crossover study, and 31 completed the
      study. On seven separate occasions separated by at least 6 days, the children
      received a single morning dose of d-MPH (2.5, 5, or 10 mg), d,l-MPH (5, 10, or 20
      mg), or placebo and then were observed in a laboratory classroom setting for 8
      hours. At specified intervals, blinded observers rated behavior, and the children
      performed a computerized math test. The plasma levels of MPH were related to the
      response to study medication. The safety profiles of the two formulations were
      compared. RESULTS: For both formulations, the responses to both MPH preparations
      were dose related, the plasma concentrations of l-MPH were negligible and of d
      MPH were indistinguishable, and clinical efficacy was highly correlated with
      plasma concentrations of d-MPH. The efficacy of the d-isomer was equivalent to
      the racemic preparation in reducing ADHD symptoms and increasing academic
      productivity. CONCLUSIONS: The efficacy of MPH resides in the d-isomer. The
      elimination of the l-isomer does not diminish the efficacy of an acute dose of
      methylphenidate.

PMID- 15502604
TI  - Case study: successful medication withdrawal using cognitive-behavioral therapy
      for a preadolescent with OCD.
AB  - The aim of this study was to evaluate the effectiveness of the addition of manual
      based cognitive-behavioral therapy to a medication regimen of clomipramine and
      fluoxetine and the withdrawal of medication during cognitive-behavioral therapy.
      The participant was an 11-year-old girl with symptoms of obsessive thoughts about
      germs and illness and handwashing compulsions. The addition of cognitive
      behavioral therapy reduced the participant's daily number of obsessions and
      avoidance behaviors after three sessions. When medication was tapered during the
      cognitive-behavioral therapy program, the participant's symptoms continued to
      decline, and after treatment, she no longer met diagnostic criteria for obsessive
      compulsive disorder. Impressively, the participant remained medication free and
      treatment gains were maintained at 4 months' follow-up.

PMID- 15502605
TI  - Early diagnosis of Asperger's disorder: lessons from a large clinical practice.

PMID- 15502608
TI  - Architecture of the lung: morphology and function.
AB  - The architecture of the lung is discussed with special focus on lung parenchyma.
      The lung parenchyma is mainly comprised of numerous air-containing passages and
      intervening fine structures, corresponding to alveolar ductal lumens and alveoli,
      as well as alveolar septa and small pulmonary vessels occupying 10% of total
      parenchymal volume. The shapes and relative arrangements of alveolar ducts and
      alveoli are discussed in detail, which is followed by a brief description of
      bronchial circulation and pulmonary lymphatics.

PMID- 15502609
TI  - Functional magnetic resonance imaging of the lung: a physiological perspective.
AB  - Functional lung imaging has the potential to offer many new insights into
      mechanisms of pulmonary disease. While the physiologist has access to a number of
      techniques to evaluate lung function, such as multiple inert gas elimination
      technique or the injection of microspheres, these techniques have significant
      disadvantages, including lack of spatial information or low spatial resolution
      and, in the case of microspheres, an inability to make measurements in humans.
      The functional imaging techniques based on magnetic resonance (MR), computed
      tomography (CT), or positron emission tomography (PET) hold substantial promise.
      In this article, specific issues related to the MR evaluation of pulmonary blood
      flow, including quantification of heterogeneity, reliability, and validity of the
      technique, are discussed to highlight some of the important physiologic issues
      that affect functional imaging. Additional physiologic considerations include the
      anatomic partitioning of blood flow, and the effects of posture, breath holding,
      and exercise. The relationships between these many factors and the collection of
      regional pulmonary perfusion data are explored.

PMID- 15502610
TI  - Quantitative CT of emphysema and the airways.
AB  - Chronic lung disease is a leading cause of morbidity and mortality in the United
      States. Quantitative techniques for assessing emphysema and related airway
      disease have been slow to gain acceptance among radiologists, who have
      traditionally used description of structural changes to evaluate these diseases.
      This review provides an overview of these quantitative techniques.

PMID- 15502611
TI  - MR evaluation of pulmonary blood flow.
AB  - Pulmonary blood flow is one of the primary determinants of gas exchange. While a
      number of methods can be used to evaluation pulmonary perfusion, these have
      substantial limitations. In this paper, we discuss the use of magnetic resonance
      imaging techniques for the evaluation of pulmonary blood flow. While these
      methods are not commonly used at present, they have the potential to contribute
      greatly to the evaluation of suspected pulmonary vascular disease.

PMID- 15502612
TI  - Hyperpolarized gas MR imaging of the lung.
AB  - Hyperpolarized gases belong to a new class of MR contrast agents that, when
      inhaled, provide high temporal and spatial resolution images of the lung
      airspaces. At this time, hyperpolarized gas MRI is only being performed at a
      limited number of institutions. However, the availability of hyperpolarized gas
      MRI could increase dramatically in coming years as regulatory hurdles within the
      U.S. are surmounted. The intent of this paper is to provide an introduction to
      hyperpolarized gas MRI for the thoracic radiologist. It includes a description of
      the basic principles of hyperpolarized gas MRI and a review of the results of
      preliminary clinical investigations with this method.

PMID- 15502613
TI  - Pulmonary abnormalities in ankylosing spondylitis: inspiratory and expiratory
      high-resolution CT findings in 17 patients.
AB  - OBJECTIVE: The purpose of this study was to evaluate pulmonary manifestations of
      ankylosing spondylitis on inspiratory and expiratory high resolution CT. MATERIAL
      AND METHODS: The study included 17 patients ranging from 40 to 62 years in age.
      Fifteen patients were male, and 8 were smokers. All patients underwent chest
      radiography and high-resolution CT. High-resolution CT was obtained using 1 or 2
      mm collimation scans at 10-mm intervals at the end of maximal inspiration and at
      3 cm intervals at the end of maximal expiration. RESULTS: Pulmonary abnormalities
      were evident on chest radiography in 2 patients and on CT in 15 patients. The
      abnormalities on CT included evidence of airway disease in 14 (82%), interstitial
      abnormalities in 11 (65%), and emphysema in 6 (35%) patients. Airway
      abnormalities included bronchial wall thickening in 7 (41%), mosaic perfusion in
      3 (18%), centrilobular nodules in 3, bronchiolectasis in 2, and air trapping on
      expiratory CT in 7 (41%) patients. Interstitial abnormalities included
      parenchymal bands in 7 (41%), intralobular linear opacities (n = 2), and 1
      patient each with irregular thickening of interlobular septa, subpleural lines,
      and honeycombing. CONCLUSION: The majority of patients with ankylosing
      spondylitis have airway and interstitial abnormalities evident on high-resolution
      CT. These abnormalities are usually mild and therefore seldom evident on the
      chest radiograph.

PMID- 15502614
TI  - Radiopaque pulmonary arteries on chest radiography.
AB  - We report a case of a 58-year-old male with cirrhosis and upper gastrointestinal
      bleeding who developed multiple lipiodol pulmonary emboli after endoscopic
      injection sclerotherapy for gastric variceal bleeding. The patient did not have
      any respiratory symptoms after the sclerotherapy. A chest radiograph, obtained 1
      day after the procedure for the evaluation of fever, demonstrated multiple
      tubular radiopacities in both hilar regions. CT confirmed the existence of
      multiple radiopaque emboli within the main pulmonary arteries, a small pleural
      effusion, and no evidence of associated pulmonary parenchymal changes. The
      patient had no further symptoms, and the radiologic opacities persisted on
      radiographs obtained 3 months later.

PMID- 15502617
TI  - Memorable Medical Mentors: VII: Louis M. Hellman (1908-1990).

PMID- 15502629
TI  - Congenital hypofibrinogenemia in pregnancy: report of two cases and review of the
      literature.
AB  - Fibrinogen abnormalities have been implicated in many adverse pregnancy outcomes,
      mainly spontaneous abortion, placental abruption, and postpartum hemorrhage. Two
      new cases of congenital hypofibrinogenemia in pregnancy are reported detailing
      their obstetric course and management. The relevant obstetric and hematologic
      literature is reviewed, including previous case reports and studies concerning
      the mechanisms of pregnancy complications. Suggestions for treatment guidelines
      and management strategies are detailed.

PMID- 15502630
TI  - Contemporary clinical issues in outpatient obstetrics and gynecology: findings of
      the Collaborative Ambulatory Research Network, 2001-2004: part I.
AB  - Obstetrician/gynecologists are taking on more primary care responsibilities and
      thus are expected to have a wider base of medical knowledge on a variety of
      women's health issues. The Collaborative Ambulatory Research Network (CARN) was
      created in 1990 to investigate issues pertinent to women's health and to the
      practice of obstetrics and gynecology in the outpatient setting. This article
      summarizes the findings of CARN studies from 2001 to 2004, covering topics of
      infectious diseases, cancer screening, and metabolism and nutrition. Each study
      provides a glimpse into the current practice patterns, attitudes, and knowledge
      of the practicing obstetrician/gynecologist. Although aggregate results suggest
      that clinicians are consistent and knowledgeable in traditional areas of
      practice, there appears to be a need for comprehensive educational programs to
      increase clinicians' comfort level with and knowledge of many contemporary
      primary care issues.

PMID- 15502631
TI  - Contemporary clinical issues in outpatient obstetrics and gynecology: findings of
      the Collaborative Ambulatory Research Network, 2001-2004: part II.
AB  - Obstetrician/gynecologists are taking on more primary care responsibilities and
      thus are expected to have a wider base of medical knowledge on a variety of
      women's health issues. The Collaborative Ambulatory Research Network (CARN) was
      created in 1990 to investigate issues pertinent to women's health and to the
      practice of obstetrics and gynecology in the outpatient setting. This article
      summarizes the findings of CARN studies from 2001 to 2004, covering topics of
      abnormal pregnancy outcomes, complications of pregnancy, and psychologic
      disorders. Each study provides a glimpse into the current practice patterns,
      attitudes, and knowledge of the practicing obstetrician/gynecologist. Although
      aggregate results suggest that clinicians are consistent and knowledgeable in
      traditional areas of practice, there appears to be a need for comprehensive
      educational programs to increase clinicians' comfort level with and knowledge of
      many primary care issues.

PMID- 15502635
TI  - Glucose stimulates the association of Crk with p130Cas in pancreatic beta cells.
AB  - OBJECTIVES: Previously, we demonstrated glucose-induced beta-cell tyrosine
      phosphorylation of p130Cas, a protein containing 15 YXXP repeats that can become
      tyrosine phosphorylated and bind Src-homology 2 (SH2)-containing proteins. In
      light of the importance of p130Cas in other cell types, we determined which beta
      cell proteins exhibited glucose-induced association with p130Cas. METHODS: beta
      cells were stimulated with glucose and/or the muscarinic agonist carbachol to
      determine which SH2-containing adapter proteins underwent glucose-induced
      association with p130Cas. RESULTS: The SH2-containing adapter protein Crk
      underwent glucose-induced association with p130Cas, while other SH2-containing
      proteins such as grb2, PI3 kinase, Shp-2, paxillin, and pyk2 did not. Glucose
      induced Crk-p130Cas association was rapid and sustained and was maximal with the
      combination of glucose and carbachol, paralleling insulin secretion. There was no
      increased tyrosine phosphorylation of Crk itself. The expression of Crk in
      isolated rat islets was also demonstrated. CONCLUSION: beta cells contain the SH2
      containing adapter protein Crk, which undergoes glucose-induced association with
      p130Cas.

PMID- 15502636
TI  - Changes in IP3 receptor are associated with altered calcium response to
      cholecystokinin in diabetic rat pancreatic acini.
AB  - OBJECTIVES: Pancreatic acini of diabetic rats release amylase less than normal
      acini on cholecystokinin (CCK) stimulation. Pancreatic enzyme secretion by CCK is
      closely related to the second messenger inositol 1,4,5-trisphosphate (IP3), which
      mobilizes intracellular calcium stores via the endoplasmic reticulum-located
      receptor IP3 (IP3R). Recently, we observed altered intracellular calcium response
      on CCK-8 stimulation in streptozotocin (STZ)- treated diabetic rat acini.
      METHODS: To determine whether IP3R is involved in altered calcium response, we
      measured inositol phosphate (IP) formation and the expression and phosphorylation
      of type III IP3R protein in diabetic acini. Also, CCK receptor mRNA expression
      was examined to determine whether the changes in IP formation and IP3R protein
      phosphorylation in diabetic acini might result from the defect at the
      postreceptor level. RESULTS: CCK-8-induced IP formation at all concentrations
      used was significantly reduced in diabetic acini, though IP formation was
      increased in a concentration-dependent manner. The expression of type III IP3R
      protein was significantly reduced in diabetic acini. Additionally, CCK-8
      stimulated phosphorylation of type III IP3R protein was not observed in diabetic
      acini. However, the reduction of CCK receptor mRNA expression was not detected in
      diabetic acini. CONCLUSION: Our results indicate that altered calcium response to
      CCK-8 in diabetic acini might be associated with a post-CCK receptor defect
      including the changes in IP formation, type III IP3R protein expression, and
      phosphorylation of type III IP3R protein.

PMID- 15502637
TI  - The Influence of a load of L-arginine on serum amino acids and pancreatic
      apoptosis/proliferation and ATP levels in the rat.
AB  - OBJECTIVES: Administration of high doses of amino acids like ethionine,
      methionine, and arginine causes pancreatic tissue damage. The initial mechanism
      behind these effects is not known. The aim of this study was to show the early
      effects of a load of L-arginine on programed cell death/proliferation and ATP
      levels in the pancreas. METHODS: We analyzed in rats the effects of
      intraperitoneal administration of L-arginine on serum amino acids, pancreatic
      cell apoptosis/proliferation, and ATP levels at 8, 16, and 24 hours. Serum amino
      acid concentrations were measured with HPLC, tissue ATP was measured
      fluorometrically, apoptosis was studied with caspase-3 activity and histone
      associated DNA-fragments, and proliferation was studied with thymidine
      autoradiography. RESULTS: After a load of l-arginine, there were initially
      increased serum levels of L-arginine and L-citrulline, but these fell below
      control levels after 24 hours as well as amino acids in the glutamate family
      (ornithine, proline, histidine, and glutamine). Initially, increased ATP levels
      in the pancreatic tissue returned to control levels at 24 hours. The acinar cells
      proliferation was suppressed and the apoptosis rate strongly increased at 16 and
      24 hours. Pancreatic histology showed vacuole formation in the acinar cells at 8
      hours. At 16 hours, there was less vacuolization, but apoptotic bodies were seen,
      and at 24 hours there was cell degeneration but no necrosis. CONCLUSIONS: After a
      load of l-arginine, amino acid metabolism causes a high ATP production in the
      pancreatic tissue that may cause mitochondrial initiation of cell death.

PMID- 15502638
TI  - Effects of cholinergic m-receptor agonists on insulin release in islets from
      obese and lean mice of different ages: the importance of bicarbonate.
AB  - OBJECTIVES: Decreased beta-cell function is often observed in older individuals
      and may predispose to the development of type 2 diabetes. We have studied the age
      related effects of M-receptor agonism on insulin release in islets isolated from
      female ob/ ob and lean mice. METHODS: Islets were challenged with 11.1 or 16.7
      mmol/L glucose in media with HCO3/CO2 (KRBH) or without (KRH). RESULTS:
      Acetylcholine (ACh) (10 micromol/L) increased glucose-induced insulin release in
      islets from 4- to 5-week-old ob/ob mice both in KRBH and KRH. In islets from 9-
      to 13-month-old ob/ob mice, 10 micromol/L ACh and 10 micromol/L carbachol
      enhanced insulin release in KRBH but not in KRH. ACh increased insulin release in
      islets from 4- to 5-week-old and 16-month-old lean mice incubated in KRH but not
      in islets from 24-month-old lean mice. The Na/H exchange inhibitor
      dimethylamiloride (100 micromol/L) did not affect insulin release stimulated by M
      receptor agonists. Carbachol did not enhance glucose-induced insulin secretion in
      islets from 9- to 10-month-old ob/ob mice in the presence of low extracellular Na
      concentration. ACh stimulated cytoplasmic Ca mobilization in islets from 9- to 10
      month-old mice also when bicarbonate was omitted. The results suggest that
      cholinergic signal transduction involving extracellular bicarbonate and Na is
      reduced with age in mouse pancreatic islets. CONCLUSION: Chronic hyperglycemia
      may add to the age-related decrease in M-receptor-mediated insulin release by
      affecting the buffering capacity of the islets through mechanisms other than
      amiloride-sensitive proton exchange.

PMID- 15502639
TI  - COX and PPAR: possible interactions in pancreatic cancer.

PMID- 15502640
TI  - The molecular basis of pancreatic fibrosis: common stromal gene expression in
      chronic pancreatitis and pancreatic adenocarcinoma.
AB  - OBJECTIVES: Tissue desmoplasia occurs in a number of disease states, but its
      molecular basis is poorly understood. To determine which genes are overexpressed
      in cells contained within the desmoplastic stroma of pancreatic adenocarcinoma
      and chronic pancreatitis, we undertook genetic profiling of microdissected tissue
      samples of pancreatic adenocarcinoma, chronic pancreatitis, normal pancreas, and
      pancreatic cancer cell lines. We observed that samples of both pancreatic
      adenocarcinoma and chronic pancreatitis showed elevated expression of many shared
      genes compared with the normal pancreas. We hypothesized that these common genes
      likely important in stromal production and/or function could be identified using
      a strategy that involved comparisons between pancreatic adenocarcinoma, chronic
      pancreatitis, normal pancreas, and pancreatic cancer cell lines. METHODS: We
      performed oligonucleotide microarray analysis of 6800 different genes expressed
      in 10 samples of pancreatic adenocarcinoma, 5 samples of normal pancreas, 5
      samples of chronic pancreatitis, and 7 pancreatic cancer cell lines. Microarray
      findings were validated with RT-PCR, and immunohistochemistry was used to verify
      protein localization to the stromal compartment of both pancreatic cancer and
      chronic pancreatitis. RESULTS: We employed a deductive comparison whereby genes
      expressed in the normal pancreas and pancreatic cancer cell lines were
      selectively eliminated from those expressed in common by pancreatic
      adenocarcinoma and chronic pancreatitis. This strategy identified 107 genes
      predicted to be expressed within cells of the stromal compartment of both
      pancreatic adenocarcinoma and chronic pancreatitis. CONCLUSIONS: These genes are
      likely important factors in epithelial-stromal signaling in pancreatic
      desmoplasia and may serve as diagnostic or therapeutic targets.

PMID- 15502641
TI  - Angiotensin II mediates acinar cell apoptosis during the development of rat
      pancreatic fibrosis by AT1R.
AB  - OBJECTIVES: The mechanisms of pancreatic fibrosis were not fully elucidated.
      Apoptosis has been suggested to be involved in the progression of pancreatic
      fibrosis. It has been reported that the renin-angiotensin system (RAS) plays a
      crucial role in the formation of fibrosis, including in the kidney, heart, and
      liver. We recently reported that the angiotensin II type I receptor (AT1R)
      antagonist losartan has been able to alleviate the pancreatic fibrosis in the rat
      model, indicating angiotensin II participated in the progression of pancreatic
      fibrosis. In present study, the possible effects of angiotensin II-mediated
      apoptosis of pancreatic acinar cells were investigated in rat pancreatic fibrosis
      induced by trinitrobenzene sulfonic acid (TNBS) by AT1R, with special reference
      to the losartan administration. METHODS: Male Sprague-Dawley rats (200-300 g)
      were randomly divided into a normal group, a control group, and a losartan
      treatment group. Pancreatic fibrosis was induced by infusion of 2% TNBS into the
      pancreatic duct. Rats were treated with losartan (10 mg/kg) by gavage daily in
      the losartan-treatment group and the same volume of sterile distilled water was
      administered to the control group. All treatments started on the first day and
      ended 8 weeks after the operation. On day 3 and at weeks 1, 2, 3, 4, and 8, the
      histologic changes of the pancreas were examined by hematoxylin and eosin
      staining, and pancreatic acinar cell apoptosis was investigated by using electron
      microscopy and terminal deoxynucleotidyl transferase UTP nick end labeling
      (TUNEL), indicated by the apoptotic index (AI). Expressions of Bax, Bak, and Bcl
      2 mRNA in the pancreas were detected by reverse transcriptase polymerase chain
      reaction (RT-PCR) on day 3 and at weeks 1, 2, 3, and 4. RESULTS: Compared with
      the control group, losartan treatment significantly alleviated the histologic
      abnormalities, including infiltration of inflammatory cells and acinar cells
      atrophy. In the control group, a typical morphologic presentation of acinar cell
      apoptosis was seen either with electron microscopy or TUNEL staining. The AI was
      increased in pancreatic tissue. Meanwhile, Bax and Bak mRNA expression was
      increased, but Bcl-2 mRNA expression was decreased, as compared with the normal
      group. The administration of losartan resulted in inhibition of acinar cell
      apoptosis and down-regulation of Bax, Bak, and Bcl-2 mRNA expression. The Bax/Bcl
      2 ratio was lower in losartan-treated rats than in control rats. CONCLUSION:
      Losartan prevents apoptosis of pancreatic acinar cell by blocking AT1R during the
      development of pancreatic fibrosis. This action may be associated with its
      regulation of apoptosis-associated genes, such as Bax, Bak, and Bcl-2 mRNA. The
      results of present study suggest that angiotensin II probably mediates pancreatic
      acinar cell apoptosis during the course of pancreatic fibrosis.

PMID- 15502642
TI  - The functional significance of the cholecystokinin-C (CCK-C) receptor in human
      pancreatic cancer.
AB  - OBJECTIVES: The aim of this study was to evaluate whether the CCK-C receptor, a
      splice variant of the CCK-B receptor, in human pancreatic cancer cells was
      associated with accelerated cancer cell growth. METHODS: In vitro, BxPC-3 cells
      were transfected with the antisense cDNA for the CCK-C receptor and growth of
      transfected cells was compared with that of wild-type (WT) and empty vector (EV)
      transfected cells; expression was confirmed by RT-PCR and immunocytochemistry. In
      vivo, athymic nude mice bearing human BxPC-3 pancreatic cancers were treated for
      28 days with either an antisense oligonucleotide specific to the CCK-C receptor,
      the same nucleotide sequence arranged in a scrambled fashion (nucleotide
      control), or vehicle (control). RESULTS: In culture, BxPC-3 cells transfected
      with the antisense cDNA for the CCK-C receptor were reduced in cell number 65%
      compared with WT and EV-transfected cell cultures at 6 days; this difference was
      statistically significant (P = 0.002). Transfected cells did not respond to
      exogenous gastrin with growth as did WT cells. Tumors of mice treated with the
      antisense oligonucleotide for CCK-C were 75% smaller in volume and 83% reduced in
      weight (P = 0.03) compared with the control tumors. CONCLUSION: These studies
      indicate that the CCK-C receptor is functional and plays a crucial role in growth
      of human pancreatic cancer.

PMID- 15502643
TI  - Fibroblast growth factor-2 stimulates interleukin-6 secretion in human pancreatic
      periacinar myofibroblasts.
AB  - OBJECTIVES: Fibroblast growth factor-2 (FGF-2) plays an important role in the
      pathophysiology of acute and chronic pancreatitis. In the present study, to
      evaluate the proinflammatory nature of FGF-2, we investigated the effects of FGF
      2 on IL-6 secretion in human pancreatic periacinar myofibroblasts. METHODS: IL-6
      supernatant levels were determined by enzyme-linked immunosorbent assays (ELISA).
      IL-6 mRNA expression were determined by Northern blots and quantitative PCRs.
      Activated protein (AP)-1 DNA-binding activities were evaluated by electrophoretic
      gel mobility shift assays (EMSA). RESULTS: FGF-2 induced IL-6 release in a dose-
      and time-dependent manner. FGF-2 activity for IL-6 induction was the same as that
      of IL-17. The combination of FGF-2 and IL-17 exerted additive effects at mRNA and
      protein levels. FGF-2 induced AP-1 DNA-binding activity, but blockage of AP-1
      signaling by adenovirus-mediated transfer of a dominant negative c-Jun gene did
      not affect FGF-2-induced IL-6 mRNA expression. FGF-2 rapidly induced activation
      of ERK1/2 and p38 MAP kinases, and specific inhibitors for these enzymes
      significantly reduced FGF-2-induced IL-6 release. CONCLUSION: In the pancreas,
      FGF-2 may not only play a role as a growth factor in tissue injury repair
      processes but also as an inducer of acute-phase response via stimulation of IL-6
      release.

PMID- 15502644
TI  - Expression of connexin26 in islets of Langerhans is associated with impaired
      glucose tolerance in patients with pancreatic adenocarcinoma.
AB  - OBJECTIVES: Impairment of glucose tolerance is one of the leading clinical
      presentations in patients with pancreatic carcinoma. The mechanism of disturbed
      glucose metabolism, however, is still under debate. Using microarray technology,
      key mechanisms of deregulated molecular functions of cancer cell-specific mRNAs
      and tumor-induced mRNAs in peritumorous tissue should be identified in pancreatic
      ductal adenocarcinoma (PDAC) by comparison to chronic pancreatitis and normal
      pancreas. METHODS: Forty-three mRNAs were abundant in tissue specimens of
      patients operated due to pancreatic carcinoma but absent or of low abundance in
      chronic pancreatitis and normal pancreas. One of these mRNAs encodes the gap
      junction protein connexin26, known as a tumor suppressor, which was 10.8- and 6.9
      fold more abundant in pancreatic carcinoma than in normal pancreas and chronic
      pancreatitis, respectively. Quantitative RT-PCR was performed for connexin26,
      with mRNA being expressed 26.7- and 2.9-fold more than in normal pancreas (n =
      6), in pancreatic carcinoma (n = 7), and chronic pancreatitis (n = 8),
      respectively. RESULTS: By immunohistochemistry, connexin26 was predominantly
      localized to the islets in the vicinity of the pancreatic carcinoma tissue.
      Control sections of tissue with chronic pancreatitis and normal pancreas show
      connexin26 expression in the islets as well. Interestingly, the level of mRNA
      abundance (fold over normal pancreas) in RT-PCR correlates (r = 0.62) with the 2h
      value of the pre-operative oral glucose tolerance test of these patients.
      CONCLUSION: Whether overexpressed connexin26 in pancreatic cancer is a cause of
      impaired glucose tolerance remains to be elucidated in further experimental
      studies.

PMID- 15502645
TI  - Extrapancreatic manifestations of acute pancreatitis in African-American and
      Hispanic patients.
AB  - OBJECTIVE: Many studies have been published on acute pancreatitis but few, if
      any, on extrapancreatic manifestations (EPM) in African Americans and Hispanics.
      We studied the effect of EPM on mortality in these 2 ethnic groups. METHODS:
      Records of 760 acute pancreatitis patients (417 African-American and 343
      Hispanic), ages 19-85 years, over a 15-year period were reviewed retrospectively.
      Data were analyzed for EPM and mortality. RESULTS: Of the 760 patients, alcohol
      use was identified as the etiology in 53% of cases and gallstones in 42%. EPM
      were present in 148 patients (19.5%). Gastrointestinal bleeding (22%) was the
      most common EPM. Patients with EPM did not differ from patients without EPM on
      demographics or acute pancreatitis-related variables (P > 0.05). Patients with
      EPM had higher odds of having comorbidity relative to patients without EPM (OR =
      2.9, CI = 2.0-4.2). Of 760 patients, 109 died (14%). However, mortality was
      significantly higher (26%) in patients with EPM in comparison to those without
      EPM (11%), P = 0.001. Controlling for other variables, patients with EPM had
      higher odds of mortality relative to patients without EPM (OR = 2.8, CI = 1.7
      4.4). CONCLUSION: Mortality was high in our patients compared with the literature
      (5%-10%). EPM increased the mortality significantly (26%).

PMID- 15502646
TI  - Serum trypsinogen activation peptide in the assessment of the diagnosis and
      severity of acute pancreatic damage: a pilot study using a new determination
      technique.
AB  - OBJECTIVES: To evaluate the clinical value of a new direct and competitive
      immunoassay for trypsinogen activation peptide (TAP) determination in acute
      pancreatitis (AP). METHODS: The subjects were 34 patients with AP (22 mild, 12
      severe), 12 patients with nonpancreatic acute abdominal pain (AA), 11 healthy
      subjects (HS), and 16 consecutive patients who underwent therapeutic ERCP (ERCP).
      Serum TAP, amylase, and lipase levels were determined in AP, AA, and HS at their
      initial observation; the AP patients were also studied for 6 consecutive days
      after admission. In the ERCP patients, serum TAP, amylase, and lipase levels, as
      well as urine TAP and amylase levels, were determined before and 6 hours after
      endoscopy. RESULTS: Serum TAP levels on admission were 0.35 +/- 1.60 OD (mean +/-
      SD) in AP patients and 0.005 +/- 0.001 OD in AA patients, while HS patients had
      no detectable serum TAP levels. ERCP patients had no detectable serum TAP levels
      before and 6 hours after the ERCP, whereas urine TAP concentrations were 1.72 +/-
      3.43 OD and 0.75 +/- 1.49 OD before and 6 hours after the execution of the
      endoscopy, respectively (P = 0.249). The sensitivities and specificities of serum
      TAP, amylase, and lipase levels in discriminating between AP and AA were 23.5%
      and 91.7%, 94.1% and 100%, and 97.1% and 100%, respectively, while those used in
      the assessment of the severity of AP were 29.9% and 73.5%, 38.8% and 81.2%, and
      28.4% and 83.6%, respectively. CONCLUSION: TAP is of limited value in assessing
      the diagnosis and the severity of acute pancreatic damage.

PMID- 15502647
TI  - Hydrogen breath test with low-dose rice flour for assessment of exocrine
      pancreatic insufficiency.
AB  - OBJECTIVES: The hydrogen (H2) breath test is widely used in the assessment of
      carbohydrate malabsorption. Severe exocrine pancreatic insufficiency markedly
      diminishes pancreatic amylase production and results in malabsorption of complex
      carbohydrates. Thus, the H2 breath test with low-dose rice flour starch was
      tested to determine its value in detecting exocrine pancreatic insufficiency by
      comparison with a direct measurement of pancreatic function. METHODS: Ten
      patients with clinically suspected pancreatic insufficiency confirmed with a
      duodenal perfusion technique and measurement of trypsin and lipase output after
      cerulein stimulation were included. An H2-rice flour breath test was performed by
      orally administering 30 g of rice flour. End-alveolar breath samples were
      obtained before rice load and at 30-minute intervals thereafter for the next 5
      hours. RESULTS: The results are expressed as median (percentile 25-75). Patients
      included 8 men and 2 women with moderate to severe exocrine pancreatic
      insufficiency due to chronic pancreatitis, pancreatectomy, or cystic fibrosis.
      Stimulated duodenal output of lipase and trypsin was abnormally low in all
      patients (median release, 1.7; range, 0.5-4.5 and 0.8, range, 0.1-11.3 KU/h,
      respectively). Basal H2 excretion was 9 ppm (range, 7-17) and delta increase over
      basal H2 excretion was 4 ppm (range, 1-6). Correlation between H2-rice breath
      test and basal or stimulated duodenal output of lipase and trypsin was not
      significant. CONCLUSION: In exocrine pancreatic insufficiency, an oral load of 30
      g rice flour slightly raises H2 excretion in breath. This increase is not useful
      for detecting pancreatic insufficiency due to poor sensitivity and because it is
      influenced by extrapancreatic factors such as small bowel bacterial overgrowth.

PMID- 15502648
TI  - Diabetes mellitus influences the degree of colocalization of calcitonin gene
      related peptide with insulin and somatostatin in the rat pancreas.
AB  - OBJECTIVES: Although calcitonin-gene related peptide (CGRP) (C162H262N50O50S2)
      has been shown to be present in pancreatic islet cells, no data have been
      reported on the pattern of its distribution in the islets of Langerhans of
      diabetic rats. METHODS: The present study used immunohistochemical and
      immunofluorescence techniques to examine the pattern of distribution of CGRP-like
      immunoreactive (CGRP-LIR) cells and nerves in the pancreata of rats with
      streptozotocin-induced diabetes. The effect of CGRP on insulin secretion from rat
      pancreatic tissue fragments was also investigated using a radioimmunoassay
      technique. RESULTS: Numerous CGRP-LIR cells were observed in both the peripheral
      and central regions of the islets of Langerhans of normal pancreata where they
      colocalized with large and small subsets of insulin-LIR and somatostatin-LIR
      cells, respectively. By contrast, the islets of diabetic rat pancreata contained
      significantly (P < 0.0001) fewer CGRP-LIR cells compared with normal rats. In
      diabetic rat pancreata, CGRP was colocalized with larger and smaller subsets of
      somatostatin-LIR and insulin-LIR cells, respectively. CGRP-LIR nerve fibers were
      discerned in the perivascular and periacinar regions of the pancreata of both
      normal and diabetic rats. CGRP (10 M) induced a significant (P < 0.02) increase
      in insulin secretion from the pancreas of normal rat. CONCLUSION: CGRP is
      colocalized with insulin and somatostatin in the pancreata of normal and diabetic
      rats and may play an important role in the humoral and neural regulation of the
      endocrine pancreas.

PMID- 15502652
TI  - Analgesic use in children with acute abdominal pain.
AB  - STUDY OBJECTIVE: To determine the frequency of analgesic use in children (5 to 17
      years inclusive) who present to a pediatric emergency department with acute
      abdominal pain. METHODS: A retrospective medical record review of patients
      presenting to a children's hospital over a 1-year period with a chief complaint
      of abdominal pain and subsequently referred to the pediatric surgical service.
      The records were reviewed to determine emergency department analgesic use,
      patient disposition, and laparotomy rate. RESULTS: Two hundred ninety patients
      met our inclusion criteria. Of the patients seen initially by emergency
      physicians, 14.3% received analgesics, while those seen directly by the surgical
      service received analgesia 15.4% of the time. The laparotomy rate for the 290
      patients was 46.6%. CONCLUSIONS: Analgesic use in children who present to the
      emergency department with acute abdominal pain and require a surgical
      consultation was very low, although half required a laparotomy. Prospective
      studies are needed to determine the efficacy and safety of analgesic use in this
      setting.

PMID- 15502649
TI  - The HaP-T1 Syrian golden hamster pancreatic cancer model: cell implantation is
      better than tissue implantation.
AB  - OBJECTIVES: Pancreatic cancer is characterized by a poor prognosis and an
      unsatisfactory response to conventional therapy. Appropriate experimental animal
      models that mimic the disease are essential to establish new therapies. The aim
      of this study was to compare homologous orthotopic cell implantation (OCI) and
      orthotopic tissue implantation (OTI) methods in the nitrosamine-derived HaP-T1
      Syrian golden hamster pancreatic cancer model. METHODS: Pancreatic tumors were
      induced in 32 Syrian hamsters by the OCI (n = 16) and OTI (n = 16) techniques.
      OTI and OCI subgroups (n = 4) were killed at 1, 2, 5, and 8 weeks post
      implantation. Tumor uptake and growth and the rates of local invasion and
      metastases were compared at autopsy. RESULTS: Tumor uptake was 100% by OCI and
      88% by OTI. Induced pancreatic tumors were significantly larger in the OCI group
      (mean weight, 1.7 g vs. 0.26 g, P < 0.01.) The incidence of local invasion and
      rates of lymph node, liver, and peritoneal metastases were all significantly
      higher in the OCI group. CONCLUSION: The OCI method is more effective than OTI in
      terms of tumor uptake. Tumor growth and the rates of local invasion and
      spontaneous metastases are higher with OCI than OTI. The OCI method is better
      than OTI and can contribute to the development of therapeutic strategies in
      pancreatic cancer research.

PMID- 15502653
TI  - Adherence of pediatric asthma patients with oral corticosteroid prescriptions
      following pediatric emergency department visit or hospitalization.
AB  - OBJECTIVE: To determine caregiver adherence to oral corticosteroids prescribed in
      the emergency department for pediatric patients with an acute asthma exacerbation
      and to identify caregivers' perceived barriers to adherence with prescribed oral
      corticosteroids. METHOD: We conducted telephone interviews 7 to 9 days following
      a patient's presentation to an urban children's hospital emergency department for
      an acute asthma exacerbation. The telephone interview conducted with caregivers
      of pediatric asthma patients included questions regarding whether caregivers
      filled a prescription for an oral corticosteroid, the number of days the
      caregiver gave the medication, and the perceived barriers to adherence by the
      caregiver. RESULTS: During the study period, oral corticosteroid prescriptions
      were written for 161 of 172 patients completing the phone interview (93.6%). Of
      these patients, 98.7% reported filling the prescription, with caregivers of
      female patients and adolescent patients less likely to fill prescriptions than
      caregivers of male and younger patients. Asthma patient caregivers, however,
      reported adherence to the prescribed length of oral corticosteroid therapy only
      64% of the time. Caregivers worried about the side effects of oral
      corticosteroids 60% of the time. CONCLUSIONS: Efforts to increase corticosteroid
      adherence in children with acute asthma exacerbations should consider the causes
      for variation in caregiver adherence with length of therapy as well as caregiver
      perceptions regarding corticosteroid side effects.

PMID- 15502654
TI  - Comparison of the temporal artery and rectal thermometry in children in the
      emergency department.
AB  - OBJECTIVE: Rectal thermometry, the criterion standard of temperature measurement
      in young children, has numerous disadvantages. This study examined the agreement
      between rectal versus a new temporal artery professional model (TAPM) thermometer
      and rectal versus a home device temporal artery consumer model (TACM)
      thermometer, investigated if the TAPM can safely screen for rectal fever, and
      determined if parents can detect rectal fever using the TACM. DESIGN, OUTCOME
      MEASURES, AND SUBJECTS: In this cross-sectional agreement emergency department
      study, 327 children <24 months of age had their temperature measured rectally and
      by the TAPM and TACM by a single nurse and using the TACM by the parents.
      Agreements were analyzed by the Bland Altman plots. Temperature cutoff to detect
      rectal fever > or =38.0 degrees C and > or =38.3 degrees C with sensitivities of
      > or =90% and > or =95%, respectively, was determined for the TAPM. RESULTS: The
      mean difference between the rectal minus TAPM was -0.19 degrees C +/- 0.66
      degrees C, and minus the TACM home device, it was +0.11 degrees C +/- 0.66
      degrees C. The sensitivities of TAPM temperature of > or =37.7 degrees C to
      detect rectal fever > or =38.0 degrees C and > or =38.3 degrees C were 90% (95%
      confidence interval: 0.83; 0.94) and 97% (95% confidence interval: 0.92; 0.99),
      respectively. The parents detected 67% and 73% of rectal fevers 38.0 degrees C
      and > or =38.3 degrees C, respectively. CONCLUSIONS: The TAPM thermometer cannot
      replace the rectal. However, TAPM temperature of <37.7 degrees C can be safely
      used as a screen to exclude rectal fever > or =38.3 degrees C in infants 3 to 24
      months of age. The TACM home device has insufficient ability to detect rectal
      fever. A multicenter trial is needed to validate these results across multiple
      emergency departments and numerous observers.

PMID- 15502655
TI  - Emergency mental health care for youth in Washington State: qualitative research
      addressing hospital emergency departments' identification and referral of youth
      facing mental health issues.
AB  - OBJECTIVES: The purpose of this formative research was to gain a better
      understanding of how Washington State hospital emergency departments (EDs)
      identify and refer children and adolescents with mental health concerns.
      Increased understanding of emergency mental healthcare for youth will lead to the
      development and implementation of strategies and policies that enhance the system
      of providing mental health services to children and adolescents. METHODS: We
      conducted structured group interviews, a form of qualitative research, with ED,
      social work, and mental health administrators and providers in 9 hospitals in
      Washington State. RESULTS: Interviews reflected a systemwide lack of emergency
      mental health services for youth, as well as a lack of coordination between the
      larger mental health system and hospital ED. In addition, we identified issues
      specific to the hospital/ED such as insufficient availability of social work and
      mental health staff, lack of mental and behavioral health screening tools, lack
      of knowledge of available mental health services, and lack of clarity about the
      ED's role in identification of mental health concerns. CONCLUSIONS: Specific
      interventions should be developed, implemented, and evaluated to increase
      coordination between the ED and the larger mental health system. This should
      include methods for increasing ED staff knowledge of available and accessible
      mental health services for youth, perhaps through an online system. In addition,
      the role of the ED in identifying youth facing mental health issues should be
      clarified, and a brief, nonintrusive screening tool for identifying emergency
      mental health concerns should be developed.

PMID- 15502656
TI  - Effect of JumpSTART training on immediate and short-term pediatric triage
      performance.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effectiveness of
      JumpSTART training in changing prehospital care personnel and/or school nursing
      personnel performance in triaging pediatric patients involved in a multiple
      casualty incident immediately posttraining and at a 3- to 4-month follow-up
      interval. METHODS: This research involved a traditional pretest, training,
      posttest, and follow-up test format. However, since the variable of interest was
      performance rather than cognition, the measures were the individual student's
      ability to triage 10 children with simulated injuries into 1 of 4 possible
      categories within a 5-minute time window. A convenience sample of participants
      was selected from 3 divergent geographic locations. Standardized training and
      performance evaluation measures were employed. RESULTS: Significant performance
      improvements in pediatric triage were noted immediately following a 1-hour
      lecture, discussion, and case review. Changes in performance were maintained over
      a 3-month posttraining period. Prehospital personnel and school nurses benefited
      equally from pediatric triage training. CONCLUSIONS: Structured training results
      in triage performance improvement among prehospital and nursing personnel. This
      improvement is maintained for a period of at least 3 months. Additional research
      pertaining to the length of time between necessary retraining and/or refresher is
      warranted. Additionally, the relationship between staged scenario performance and
      responses to actual multiple casualty incidents needs to be established.

PMID- 15502657
TI  - Common medical terms defined by parents: are we speaking the same language?
AB  - OBJECTIVES: Physicians often assume that a patient understands frequently
      utilized medical words and patient management may be based on these assumptions.
      The objective of this study was to determine the public's definition of regularly
      used medical terminology. METHODS: A cross-sectional convenience survey was
      conducted for guardians of children presenting to an urban pediatric emergency
      department. The orally completed, open-ended questionnaire included parental
      demographic information and their definition of eleven commonly used medical
      terms. The words chosen represent common chief complaints given in our emergency
      department. Definitions were grouped, and a concordance rate of 75% was chosen to
      consider responses similar. RESULTS: One hundred twenty-two guardians completed
      the survey (89% parents, 88% female, and 55% high school graduates). Caregivers
      agreed on the definitions of diarrhea, constipation, dehydration, fever, and
      seizure. However, diarrhea and constipation were mainly defined by either stool
      consistency or frequency, not both. Dehydration was appropriately defined as lack
      of body fluids (92%), but many parents had difficulty identifying more than one
      sign of dehydration. Fever was thought to be an elevated body temperature (76%),
      yet 69% felt that a temperature less than 100.5 degrees F was considered a fever.
      Most respondents did not know the definitions of meningitis (70%), lethargy
      (64%), and virus (40%). CONCLUSIONS: Although commonly used in everyday
      conversation, there seems to be a large disparity between a caregiver's
      perception and the actual definition of medical terms. More precise communication
      may help both parties to understand the true situation.

PMID- 15502658
TI  - Intrathecal baclofen withdrawal: emergent recognition and management.
AB  - Patients with severe spasticity are frequently encountered in the pediatric
      emergency department. Intrathecal baclofen therapy is being used increasingly to
      treat these patients. The purpose of this case series is to illustrate the
      importance of early recognition and treatment of intrathecal baclofen withdrawal,
      a potentially life-threatening complication of intrathecal baclofen therapy. Four
      cases of intrathecal baclofen withdrawal are presented.

PMID- 15502659
TI  - An adolescent with chest pain-sequela of Kawasaki disease.
AB  - Kawasaki disease, is an acute vasculitis of unknown etiology characterized by
      mucocutaneous involvement occurring in infants and young children, predominantly
      younger than 5 years of age. We present a case of a 19-year-old female with a
      prior history of Kawasaki disease as an infant who was seen in the emergency
      department with chest pain in the midsternal region lasting for 20 minutes with
      radiation to the left arm. An electrocardiogram revealed anterior repolarization
      abnormalities with normal echocardiogram (ECHO) findings. There was a 90%
      eccentric and calcified single discrete stenosis of the proximal segment of the
      left anterior descending artery, and the patient underwent a successful
      percutaneous transluminal coronary angioplasty with stent insertion. Physicians
      working in the emergency department setting should remain cognescent of the rarer
      but significant cardiac causes of chest pain while evaluating children,
      adolescents, and young adults.

PMID- 15502660
TI  - An intentional opiate intoxication of an infant: when medical toxicology and
      child maltreatment services merge.
AB  - We present an instructive case of a 5-week-old infant seen in the emergency
      department with acute inspiratory stridor and depressed level of consciousness.
      His emergency department course identified an acute opiate intoxication. The
      child also developed chest wall rigidity, a rare complication of narcotic use. We
      discuss the emergency department management, as well as the toxicologic and child
      protection investigations.

PMID- 15502661
TI  - Wood's lamp employed as a provocative technique to identify pseudoseizures.
AB  - We present a case of a 12-year-old female who presented to the emergency
      department with ictal phenomena suggestive of pseudoseizures. A Wood's lamp was
      successfully employed to induce the stereotypic phenomena and thereby identify
      the ictal events as nonepileptiform. Use of the Wood's lamp has not previously
      been reported as a provocative stimulus to induce pseudoseizures. Given its
      noninvasive nature and ready availability, the Wood's lamp should be considered
      for identification of pseudoseizures.

PMID- 15502662
TI  - Young child falls on elbow (but how?).

PMID- 15502663
TI  - Motor vehicle injury prevention: current recommendations for child passenger
      safety.

PMID- 15502665
TI  - Pediatric emergency medicine: legal briefs.

PMID- 15502666
TI  - ECGs in the ED.

PMID- 15502667
TI  - Evaluation of pediatric bladder reservoir trauma.
AB  - We present a case where computed tomographic cystography of the bladder failed to
      identify a bladder rupture in a girl with an Indiana pouch after falling from her
      bicycle. Despite the normal cystogram, surgery was performed because of
      unresolving abdominal pain and free fluid identified on abdominal computed
      tomography. Upon exploration, 2 intraperitoneal ruptures were identified. While
      computed tomographic cystography is accurate for the evaluation of trauma in a
      normal bladder, emergency room physicians should be aware of its potential
      inaccuracy in patients with bladder reservoirs.

PMID- 15502668
TI  - "RSI"--is it rapid sequence induction or rapid sequence intubation?

PMID- 15502669
TI  - Comparison of methods to increase repeat testing in persons treated for gonorrhea
      and/or chlamydia at public sexually transmitted disease clinics.
AB  - BACKGROUND: Retesting 3 to 4 months after treatment for those infected with
      chlamydia and/or gonorrhea has been recommended. GOAL: We compared various
      methods of encouraging return for retesting 3 months after treatment for
      chlamydia or gonorrhea. STUDY: In study 1, participants were randomly assigned
      to: 1) brief recommendation to return, 2) intervention 1 plus $20 incentive paid
      at return visit, or 3) intervention 1 plus motivational counseling at the first
      visit and a phone reminder at 3 months. In study 2, participants at 1 clinic were
      randomly assigned to 4) intervention 1, 5) intervention 1 plus phone reminder, or
      6) intervention 1 plus motivational counseling but no telephone reminder.
      RESULTS: Using multiple logistic regression, the odds ratios for interventions 2
      and 3, respectively, compared with intervention 1 were 1.2 (95% confidence
      interval [CI], 0.6-2.5) and 2.6 (95% CI, 1.3-5.0). The odds ratios for
      interventions 5 and 6 compared with intervention 4 were 18.1 (95% CI, 1.7-193.5)
      and 4.6 (95% CI, 0.4-58.0). CONCLUSIONS: A monetary incentive did not increase
      return rates compared with a brief recommendation. A reminder phone call seemed
      to be the most effective method to increase return.

PMID- 15502670
TI  - Self-reported symptoms of reproductive tract infections among rural women in
      Hainan, China: prevalence rates and risk factors.
AB  - OBJECTIVES AND GOAL: The goal of this study was to examine risk of reproductive
      tract infections (RTIs) among women in rural China, including prevalence,
      influence of sociodemographic characteristics, knowledge, hygienic practices,
      attitudes, and behaviors related to premarital and extramarital sex, and
      abortion. STUDY: During 2000, a stratified cluster sample of 606 rural married
      women in Hainan province completed an interviewer-administered standardized
      questionnaire. RESULTS: Overall, 39% of participants reported at least 1 RTI
      symptom in their lifetime and 20% during the past 6 months. Having had premarital
      sex, having sex during menstruation, belonging to an ethnic minority, being
      knowledgeable about RTIs, and living in a village at medium economic level were
      all related to having RTI symptoms. CONCLUSION: Among married women in rural
      China, the prevalence of RTI symptoms was high, indicating the need for health
      education, particularly targeting women from ethnic minorities and resource-poor
      areas.

PMID- 15502671
TI  - Sexually transmitted disease management in Uganda's private-for-profit formal and
      informal sector and compliance with treatment.
AB  - OBJECTIVE: The objective of this study was to investigate the management of
      sexually transmitted diseases (STDs) in the Ugandan private sector clinics and
      drug shops. STUDY: Men with urethral discharge who had consulted clinics (264) or
      drug shops (141) for treatment in 5 districts were interviewed using a precoded
      questionnaire 1 to 3 weeks after initiation of treatment. RESULTS: Seventy-seven
      percent of patients sought treatment within 1 week of onset of symptoms but only
      7% were properly managed (treated according to National Guidelines, told to use a
      condom or abstain, and to refer their partner). The reported cure rate was 47%
      and only 9% were treated according to National Guidelines. Eighteen percent of
      patients used condoms during treatment, 36% persuaded their partner to go for
      treatment, and 87% completed the recommended treatment course. Of patients not
      reporting cure, 56% would still recommend the treatment to a friend. CONCLUSION:
      Quality of STD management by private providers is poor. Improvement should occur
      concurrently at public and private facilities. Possible strategies include
      training and social marketing of prepackaged treatment for STDs.

PMID- 15502672
TI  - Return for results after herpes simplex virus type 2 screening.
AB  - OBJECTIVE: The objective of this study was to evaluate factors associated with
      return for results of type-specific herpes simplex virus (HSV) screening.
      METHODS: Participants receiving type-specific HSV testing were asked to return
      for results 2 weeks after testing. Predictors of return included demographics,
      herpes-related knowledge and attitudes, and past sexual behaviors. RESULTS: A
      total of 820 sexually active subjects (age, 14-30 years; 41% male) received HSV
      screening and 578 (70%) returned for results. Higher probability of return for
      HSV testing results was significantly associated with older age (odds ratio [OR],
      1.06), female gender (OR, 1.57), enrollment at sites other than the county
      sexually transmitted disease clinic (OR, 1.70-4.71), and heightened level of
      perceived HSV vulnerability (OR, 1.07). Lower probability of return was
      associated with having more than 1 recent sex partner (OR, 0.46). CONCLUSIONS:
      Lower rates of return of high-risk patients suggest the need to focus resources
      on receipt of test results.

PMID- 15502673
TI  - Targeted screening for Trichomonas vaginalis with culture using a two-step method
      in women presenting for STD evaluation.
AB  - OBJECTIVES: Trichomonas vaginalis is the most common nonviral sexually
      transmitted pathogen. Wet mount microscopy performs poorly compared with culture;
      however, universal screening using culture would be cost-prohibitive. GOAL: The
      goal of this study was to develop a predictive model for wet mount-negative women
      who may benefit from targeted use of culture for T. vaginalis detection. STUDY:
      Women presenting for sexually transmitted disease evaluation were prospectively
      screened for trichomoniasis using wet mount and culture. Multivariate logistic
      regression was used to identify predictors of culture-proven trichomoniasis among
      wet mount-negative women. RESULTS: A total of 2194 women were screened for
      trichomoniasis; overall, the prevalence of T. vaginalis was 17.5%. Three
      predictors (any drug use, contact to trichomoniasis, and African-American race)
      provided the most specific model (100%); any 1 predictor, the most sensitive
      model (97.8%). CONCLUSIONS: Given the public health impact of trichomoniasis, we
      recommend using any 1 of 3 predictors to identify women who would benefit from
      targeted culture for T. vaginalis.

PMID- 15502675
TI  - High-risk behaviors and beliefs and knowledge about HIV transmission among school
      and shelter children in Eastern Europe.
AB  - GOAL: The goal of this study was to determine sexual behavior, injecting drug
      use, knowledge and representations of HIV transmission among adolescents in
      Russia, Georgia, and the Ukraine. STUDY: We conducted semistructured interviews
      on sexual behavior and structured inventories assessing knowledge of HIV
      transmission, sexual behavior and drug use, and social representations of the
      epidemic. RESULTS: Shelter children are more likely than school children to have
      had sex and injected drugs. Georgian school children are more likely than the
      other school children to have sex and inject drugs. Shelter children and
      Georgians are the most likely to hold mistaken representations about the
      epidemic. CONCLUSIONS: Particular groups (Russian and Ukrainian shelter children,
      Georgian school children) urgently require education about the risks of HIV/AIDS.

PMID- 15502674
TI  - Factors predicting the acceptance of herpes simplex virus type 2 antibody testing
      among adolescents and young adults.
AB  - BACKGROUND: The rates and determinants of acceptance of herpes simplex virus type
      2 (HSV-2) testing have not been adequately studied. OBJECTIVES: The objective of
      this study was to identify factors associated with acceptance of HSV-2 antibody
      testing in individuals with no history of genital herpes. STUDY: We conducted a
      cross-sectional survey study followed by the offer of free HSV-2 serologic
      testing at an urban sexually transmitted disease (STD) clinic, 2 general adult
      medical clinics, an urban university campus, and an urban adolescent medicine
      clinic. A total of 1199 individuals aged 14 to 30 years completed the survey and
      were offered testing. RESULTS: A total of 68.4% accepted HSV-2 testing. Factors
      independently associated with acceptance were female sex, older age, having an
      STD history, having 1 or more sexual partners in the last 6 months, perceived
      vulnerability to HSV-2 infection, and perceived benefits of HSV-2 testing. Fear
      of needles predicted rejection of testing, as did attending a general medical
      clinic versus an STD clinic and nonwhite race. CONCLUSION: There is a substantial
      interest in HSV-2 antibody testing across a variety of settings. Those at
      greatest behavioral and historic risk for HSV-2 infection, women, and persons
      whose health beliefs are consistent with testing are more likely to accept
      serologic testing when it is offered.

PMID- 15502676
TI  - Predictors of herpes simplex virus type 2 antibody positivity among persons with
      no history of genital herpes.
AB  - BACKGROUND: The demographic, historical, and behavioral factors that predict a
      positive herpes simplex virus type 2 (HSV-2) antibody test in persons without a
      history of genital herpes have not been well-defined. METHODS: Individuals (age
      14-30 years) without a history of genital herpes completed a questionnaire and
      were offered free HSV-2 antibody testing. Factors from the questionnaire were
      correlated with the HSV-2 antibody result. RESULTS: Univariate analysis showed
      that female gender was significantly associated with positive test results. In
      gender-specific, multiple logistic regression models, a positive HSV-2 antibody
      test among men was associated with older age, non-white race, and a history of
      sexually transmitted disease (STD). Gender-specific symptom scores from the
      questionnaire were not predictive in either gender, but the gender-common symptom
      score was marginally predictive of a positive HSV-2 antibody test in women. Among
      women, older age, non-white race, and STD history predicted a positive test.
      CONCLUSIONS: Among young persons with no history of genital herpes who agreed to
      HSV-2 antibody testing, increasing age, non-white race, and a history of an STD
      were predictors of a positive test. A history of frequent pain, itching, burning,
      and rashes in the anogenital region was marginally associated with positive HSV-2
      tests in women. These results might help guide selective use of HSV-2 antibody
      screening.

PMID- 15502677
TI  - Microbicide acceptability among high-risk urban U.S. women: experiences and
      perceptions of sexually transmitted HIV prevention.
AB  - OBJECTIVES: The objectives of this study were to measure microbicide
      acceptability among high-risk women in Hartford, Connecticut, and contextual
      factors likely to affect acceptability and use. GOAL: The goal of this study was
      to assess usefulness of microbicides for HIV/sexually transmitted infection (STI)
      prevention for high-risk women. STUDY: Ethnographic interviews (n = 75) and a
      survey (n = 471) explored women's perspectives on HIV/STI prevention, vaginal
      contraceptives similar to microbicides, and microbicide acceptability.
      Participants (n = 94) in a 2-week behavioral trial used an over-the-counter
      vaginal moisturizer to simulate microbicide use during sex with primary, casual,
      and/or paying partners. RESULTS: Findings showed limited experience with vaginal
      contraceptives, but high interest in microbicides as an alternative to condoms,
      indicated by an acceptability index score of 2.73 (standard deviation, 0.49;
      scale of 1-4) in the overall sample. General microbicide acceptability varied by
      ethnicity, prior contraceptive and violence/abuse experiences, relationship
      power, and other attitudinal factors. The simulation trial indicated significant
      willingness to use the product in various locations and with all types of
      partners. CONCLUSIONS: Vaginal microbicides may improve prevention outcomes for
      high-risk inner-city women.

PMID- 15502678
TI  - Bacterial vaginosis in lesbians and bisexual women.
AB  - OBJECTIVE: To determine whether bacterial vaginosis (BV) is associated with
      sexual activity between women. STUDY DESIGN: Cross-sectional survey of 708 new
      patients attending 2 sexual health clinics for lesbians and bisexual women in
      London, U.K. Questionnaire for demographic, sexual history, and sexual practice
      data linked with the results of genitourinary examination. RESULTS: BV was common
      (31.4%). The odds of BV was significantly associated with larger numbers of
      female sexual partners (odds ratio [OR], 1.6; confidence interval [CI], 1.05-2.44
      for > or = 11 compared with 1-5 partners) and with smoking (OR, 1.43; CI, 1.01
      2.03), but not with sex with men or vaginal douching. CONCLUSIONS: BV is common
      in women who have sex with women (WSW). The increasing odds of BV with larger
      numbers of female sexual partners suggest that BV may be sexually transmitted
      between women.

PMID- 15502679
TI  - HIV/AIDS risk among brothel-based female sex workers in China: assessing the
      terms, content, and knowledge of sex work.
AB  - BACKGROUND: Sexual transmission of HIV in China is rapidly increasing, in part
      driven by commercial sex work. GOAL: This article examines variations in
      occupational control among one type of brothel-based prostitutes in China, and
      the relationship between the terms and content of this work and the risk of
      HIV/AIDS. Organizational factors are discussed as part of the current political,
      economic, and social context of sex work in China. STUDY: The analysis is based
      on ethnographic observation and in-depth interviews conducted in south China in
      2000 and 2001 involving 158 female prostitutes from 45 brothels in 4 red light
      districts. Qualitative analysis of interview and observational data used
      development of thematic codes measuring occupational control. RESULTS: Brothel
      based female sex workers in China are a heterogeneous population, displaying
      considerable variability in the organization of life and work, relationships with
      managers and clients, ability to negotiate condom use, knowledge of sexually
      transmitted diseases and HIV, and occupational identity, all of which may result
      in different risks of acquiring HIV. CONCLUSION: HIV prevention activities in
      China must focus on sociocultural aspects of sex work. Such interventions depend
      on detailed knowledge of its organization. The results of this study demonstrate
      the importance of prevention activities directed at the brothel managers and
      clients, as well as the sex workers.

PMID- 15502680
TI  - Introduction to the special series on pain deception and malingering.

PMID- 15502681
TI  - Psychometric perspectives on detection of malingering of pain: use of the
      Minnesota Multiphasic Personality Inventory-2.
AB  - Self-report plays a primary but not exclusive role in pain assessment. As is true
      of all self-reported experiences, under certain circumstances, the report of
      chronic pain can be distorted and misrepresented. There are unique challenges
      associated with the detection and assessment of malingering or self-report
      distortion in the evaluation of chronic pain. The current paper provides a
      rationale for the use of the Minnesota Multiphasic Personality Inventory-2 (MMPI
      2) in the comprehensive assessment of chronic pain with an emphasis on the
      advantage the MMPI-2 provides in the detection of response bias or malingering. A
      critical review of available MMPI-2 validity scales is presented, and
      recommendations for use of these scales in the evaluation of patients with
      chronic pain are made.

PMID- 15502682
TI  - Critical issues in the use of muscle testing for the determination of sincerity
      of effort.
AB  - Over the past 20 years, there have been numerous attempts to identify
      methodologies that are capable of the determination of sincerity of effort during
      muscle testing. The ensuing paper reviewed this literature and drew several
      conclusions. Injured patients and healthy volunteers do produce less force and
      more variable force while performing submaximal contractions than maximal
      contractions. However, submaximal efforts during strength testing can be
      reproduced and the use of force variability is not adequate to distinguish
      sincerity of effort. Visual examination of the shape of force output curves is
      also not adequate for distinguishing sincerity of effort. Furthermore, much of
      the research using strength ratios, difference scores, and an assortment of
      different parameters derived during strength testing has not established reliable
      and clinically useful methods of differentiating effort levels. Methods examining
      motion variability, radial/ulnar force output ratios, difference scores of
      eccentric-concentric ratios, and electromyography offer some promise, but
      numerous critical issues need to addressed. The use of the coefficient of
      variation, for example, is statistically untenable given the number of trials
      appropriate for clinical samples. Several studies have inadequate sample size to
      number of variable ratios. Many studies have questionable or at least unknown
      generalizability to patient samples and actual functional capacity. It is
      critical that other explanatory variables such as fear of injury, pain,
      medications, work satisfaction, and other motivational factors be considered. It
      is our opinion that there is not sufficient empirical evidence to support the
      clinical application of muscle testing to determine sincerity of effort.

PMID- 15502683
TI  - Is there a relationship between nonorganic physical findings (Waddell signs) and
      secondary gain/malingering?
AB  - This is a structured evidence based review of all available studies addressing
      the concept of nonorganic findings (Waddell signs) and their potential
      relationship to secondary gain and malingering. The objective of this review is
      to determine what evidence, if any, exists for a relationship between Waddell
      signs and secondary gain and malingering. Waddell signs are a group of 8 physical
      findings divided into 5 categories, the presence of which has been alleged at
      times to indicate the presence of secondary gain and malingering. A computer and
      manual literature search produced 16 studies relating to Waddell signs and
      secondary gain or malingering. These references were reviewed in detail, sorted,
      and placed into tabular form according to topic areas, which historically have
      been linked with the alleged possibility of secondary gain and malingering: 1)
      Waddell sign correlation with worker compensation and medicolegal status; 2)
      Waddell sign improvement with treatment; 3) Waddell sign correlation with
      Minnesota Multiphasic Personality Inventory validity scores; and 4) Waddell sign
      correlation with physician dishonesty perception. Each report in each topic area
      was categorized for scientific quality according to guidelines developed by the
      Agency for Health Care Policy and Research. The strength and consistency of this
      evidence in each subject area was then also categorized according to Agency for
      Health Care Policy and Research guidelines. Conclusions of this review were based
      on these results. There was inconsistent evidence that Waddell signs were not
      associated with worker's compensation and medicolegal status; there was
      consistent evidence that Waddell signs improved with treatment; there was
      consistent evidence that Waddell signs were not associated with invalid paper
      pencil test; and there was inconsistent evidence that Waddell signs were not
      associated with physician perception of effort exaggeration. Overall, 75% of
      these reports reported no association between Waddell signs and the 4 possible
      methods of identifying patients with secondary gain and/or malingering. Based on
      the above results, it was concluded that there was little evidence for the claims
      of an association between Waddell signs and secondary gain and malingering. The
      preponderance of the evidence points to the opposite: no association.

PMID- 15502684
TI  - Diagnostic blocks: a truth serum for malingering.
AB  - Malingering is not a diagnosis. It is a behavior for which there are no
      established diagnostic criteria. Guidelines have been published according to
      which malingering might be suspected, but those guidelines do not discriminate
      between patients who are malingering and ones with genuine sources of chronic
      pain. In such patients, malingering cannot be proven, but it can be refuted if a
      genuine source of pain can be established. In patients with no apparent cause of
      pain, the source of that pain can be established using controlled diagnostic
      blocks. A positive response to diagnostic blocks demonstrates that the complaint
      of pain is genuine and, by implication, refutes any contention that the patient
      is malingering. When positive, diagnostic blocks provide objective data by which
      disputes based on opinion can be resolved, as to whether a patient is malingering
      or not. Negative responses do not exclude a genuine complaint of pain, for
      patients may have a source of pain that is not amenable to testing with
      diagnostic blocks. Diagnostic blocks have proved particularly useful in the
      investigation of spinal pain for which the cause is not evident on conventional
      medical imaging. They can also confirm or refute purported mechanisms of certain
      clinical features in complex regional pain syndromes.

PMID- 15502686
TI  - Malingering pain in the medicolegal context.
AB  - Malingering--the willful, deliberate, and fraudulent feigning or exaggeration of
      illness--was originally described as a means of avoiding military service. In
      present-day clinical practice, malingering may occur in circumstances where the
      person wishes to avoid legal responsibility or in situations where compensation
      or some other benefit might be obtained. In law, the term malingering is used in
      relation to persons to whom military regulations apply; in other situations,
      malingering is regarded as fraud and may lead to charges of perjury or criminal
      fraud. Assertions that an individual is malingering are particularly common in
      clinical settings where the complaint is of a subjective nature and is not
      accompanied by objectively demonstrable organic abnormalities. This may occur in
      relation to complaints of pain in situations where the person is entitled to
      receive pain-contingent compensation or is suing for damages. In this article, we
      will review the literature on pain and malingering and discuss attempts that have
      been made to develop methods and guidelines for the detection of malingered pain.
      There are, however, no valid clinical methods of assessment of possible
      malingering of pain. In our view, the ultimate issue of the veracity of the
      plaintiff is for the Court to decide, and epithets such as "malingerer" have no
      place in reports prepared for legal purposes by health care professionals.

PMID- 15502685
TI  - Detecting deception in facial expressions of pain: accuracy and training.
AB  - Clinicians tend to assign greater weight to nonverbal expression than to patient
      self-report when judging the location and severity of pain. However, patients can
      be successful at dissimulating facial expressions of pain, as posed expressions
      resemble genuine expressions in the frequency and intensity of pain-related
      facial actions. The present research examined individual differences in the
      ability to discriminate genuine and deceptive facial pain displays and whether
      different models of training in cues to deception would improve detection skills.
      Judges (60 male, 60 female) were randomly assigned to 1 of 4 experimental groups:
      1) control; 2) corrective feedback; 3) deception training; and 4) deception
      training plus feedback. Judges were shown 4 videotaped facial expressions for
      each chronic pain patient: neutral expressions, genuine pain instigated by
      physiotherapy range of motion assessment, masked pain, and faked pain. For each
      condition, the participants rated pain intensity and unpleasantness, decided
      which category each of the 4 video clips represented, and described cues they
      used to arrive at decisions. There were significant individual differences in
      accuracy, with females more accurate than males, but accuracy was unrelated to
      past pain experience, empathy, or the number or type of facial cues used.
      Immediate corrective feedback led to significant improvements in participants'
      detection accuracy, whereas there was no support for the use of an information
      based training program.

PMID- 15502687
TI  - Exaggerated pain behavior: by what standard?
AB  - This paper provides a philosophical, historical, and clinical analysis of
      exaggerated pain behavior, focusing on the nature of the standards used to judge
      behavior as exaggerated. Malingering is understood as a special case of
      exaggerated pain behavior. Drawing upon the work of philosopher Ludwig
      Wittgenstein and psychiatrist-anthropologist Horacio Fabrega, I argue that these
      standards are primarily moral rather than scientific in nature. Pain behavior is
      not validated by matching public pain behavior with private pain experience. If
      this pain experience is truly private, it is not available to scientific
      investigation. Rather, pain behavior is judged as appropriate or exaggerated
      through complex assessments of the function of this behavior in its social
      context. As human social contexts have become more complex through history, so
      have the accommodations made for sick and disabled members of the group. Criteria
      for legitimate entry to the sick role have evolved with society, with only modern
      industrial society placing heavy emphasis on tissue damage demonstrated on
      medical tests. The highly variable relation between clinical pain and tissue
      damage, as well as the common problem of medically unexplained physical symptoms
      in primary care, pose serious challenges to this strategy of illness behavior
      validation. It will remain necessary to triage suffering presented to health care
      providers into that which should be addressed in the medical setting and that
      which is better addressed elsewhere. But we need to discard pseudoscientific
      reliance on medical tests and develop new standards that are openly acknowledged
      to be moral and social in nature.

PMID- 15502688
TI  - Blood supply and oxidative metabolism in muscle biopsies of female cleaners with
      and without myalgia.
AB  - OBJECTIVES: Pathomechanisms of work-related myalgia are poorly understood.
      Myalgia is thought to be caused by excitation of nociceptors present in the
      muscular tissue but not in the muscle fiber itself. Muscle contraction in
      combination with hypoxia is known to excite nociceptors. Morphologic analysis can
      contribute to the knowledge of the excitation of nociceptors. This study
      thoroughly examines the morphology of the trapezius muscle's capillary supply and
      signs of disturbed oxidative metabolism to understand their role in work-related
      myalgia. METHODS: Surgical trapezius muscle biopsies were obtained from 25 female
      cleaners with long-standing work-related myalgia, 25 female cleaners without
      trapezius myalgia, and 21 healthy teachers. Enzyme and immunohistochemical
      stainings were performed to highlight fibers with aberrant intermyofibrillar
      patterns, indicating a disturbed oxidative metabolism (also known as moth-eaten
      fibers) and a disturbed capillary supply of different fibers. RESULTS: A
      significantly lower number of capillaries per fiber area in cleaners suffering
      from myalgia compared with cleaners without trapezius myalgia was found. Moth
      eaten fibers were found in the 3 groups, but these fibers were significantly more
      prevalent in the groups of cleaners than in the healthy teacher group.
      CONCLUSION: This work indicates that the capillary supply of trapezius is
      affected in work-related trapezius myalgia. More studies are needed to understand
      possible mechanisms that would explain the occurrence of moth-eaten fibers.

PMID- 15502690
TI  - Prognosis of multifactorial outcome in lumbar discectomy: a prospective
      longitudinal study investigating patients with disc prolapse.
AB  - OBJECTIVES: Although previous research has shown that certain medical data and
      psychosocial factors predict postoperative pain, it remains unclear whether they
      also contribute to a more distinct outcome measure that is based on
      classification of self-reported outcome criteria. To assess the prognostic power
      of somatic, psychologic, and social predictors when evident outcome criteria of
      surgical treatment are investigated, this study used a prospective longitudinal
      design examining preoperative factors associated with outcome six months after
      lumbar discectomy. METHODS: Forty-eight out of 58 consecutive patients were
      included (60% male, 40% female, mean age 47 years). Preoperative data comprised
      of Lasegue sign (straight leg raising test), pain duration, paresis and radicular
      distribution, depression, pain disability, pain coping strategies, and
      qualitative descriptions of pain. Additionally, sociodemographic and occupational
      characteristics were observed. Six months' postoperative classification of
      outcome included pain intensity, pain locations, functional capacity, return to
      work, and health-related quality of life. RESULTS: From a surgical point of view,
      lumbar discectomy was successfully carried out on all patients. But, when
      subjective criteria of outcome were investigated, 56% of patients benefited from
      lumbar discectomy, whereas 44% of patients had poor results. Lasegue sign,
      depression, and sensory pain descriptions proved to be significant predictors,
      whereas pain cognition and pain coping strategies had no significant influence on
      evident outcome classification. DISCUSSION: Classification of patients regarding
      their individual outcome profiles showed that patients responded differently to
      lumbar disc-surgery. High risk factors for poor outcome of surgery are Laseque
      sign and depression.

PMID- 15502689
TI  - Factors predicting pain reduction in chronic back and neck pain after multimodal
      treatment.
AB  - OBJECTIVES: To determine whether treatment related pain reduction on the short-
      and long-term is predicted by different baseline variables, and with different
      accuracy, in patients with chronic low back pain as compared with those with
      chronic neck pain. DESIGN AND METHODS: A single blinded prospective cohort study
      based on patients with chronic musculoskeletal pain in the lower back (N = 167)
      or the neck (N = 136) who completed a 4-week multimodal rehabilitation program.
      At admission, each patient was evaluated on 17 potential predictors, including
      pain characteristics and physical, sociodemographic, and psychosocial-behavioral
      variables. Changes in self-reported pain intensity in the lower back or the neck
      between the pretreatment evaluation and those performed immediately after, and 12
      months after the rehabilitation program, were assessed. RESULTS: Logistic
      regression models revealed that change in pain intensity could be predicted with
      good specificity but with poor sensitivity both for patients with chronic low
      back pain and chronic neck pain. Significant predictors among the neck pain
      patients were high endurance, low age, high pain intensity, few other symptoms,
      low need of being social, to do things with others, and to be helped, along with
      optimistic attitudes on how the pain will interfere with daily life. Among the
      low back pain patients, high pain intensity, low levels of pain severity, and
      high affective distress were important predictors. Variables such as sex, sick
      leave history, working status, accident, pain duration, and depressive symptoms
      demonstrated no predictive value. Short- and long-term pain outcome was equally
      predictable and predicted by almost the same variables. CONCLUSIONS: Patients who
      reported unchanged or increased pain after multimodal treatment could be
      predicted with good accuracy, whereas those who reported decreased pain were more
      difficult to identify. Treatment-related pain alteration in chronic low back pain
      seems to be predicted by partly different variables than in chronic neck pain.

PMID- 15502691
TI  - Cost benefit analysis of neurostimulation for chronic pain.
AB  - OBJECTIVES: To assess the healthcare utilization of patients with intractable
      chronic neuropathic pain treated with spinal cord stimulation and peripheral
      nerve stimulation and to provide a cost-benefit analysis. METHODS: The case
      records of 222 consecutive patients who received spinal cord stimulation or
      peripheral nerve stimulation implants at the Cleveland Clinic Foundation between
      1990 and 1998 were reviewed retrospectively. Patients were asked to complete a
      Neurostimulation Outcome Questionnaire designed to gather data on utilization of
      healthcare resources starting 1 year before surgical implantation. These data
      were pooled and net differences in events per patient per year, before and after
      device implantation were calculated and modeled to 2000 cost data obtained from
      the Medicare Fee Schedule and Healthcare Financing Administration. RESULTS:
      Neurostimulation Outcome Questionnaires were returned by 128 patients. The mean
      patient age was 46 +/- 12.5 years (range 21-71 years) and the mean implant
      duration was 3.1 +/- 2.3 years (range 0.5-8.9 years). The mean per patient total
      reimbursement of spinal cord stimulation/peripheral nerve stimulation absent
      pharmacotherapy was $38,187. Patients treated with spinal cord
      stimulation/peripheral nerve stimulation for pain management achieved reductions
      in physician office visits, nerve blocks, radiologic imaging, emergency
      department visits, hospitalizations, and surgical procedures, which translated
      into a net annual savings of approximately $30,221 and a savings of $93,685 over
      the 3.1-year implant duration. The large reduction in healthcare utilization
      following spinal cord stimulation/peripheral nerve stimulation implantation
      resulted in a net per patient per year cost savings of approximately $17,903.
      DISCUSSION: The reduced demand for healthcare resources by patients receiving
      neurostimulation suggests that peripheral nerve stimulation and spinal cord
      stimulation treatment, although associated with relatively high initial costs,
      demonstrates substantial long-term economic benefits. Thus, neurostimulation
      should be considered as a viable option for the early treatment of patients with
      intractable chronic neuropathic pain.

PMID- 15502692
TI  - Evidence, mechanisms, and clinical implications of central hypersensitivity in
      chronic pain after whiplash injury.
AB  - OBJECTIVES: To provide insights into the mechanisms underlying central
      hypersensitivity, review the evidence on central hypersensitivity in chronic pain
      after whiplash injury, highlight reflections on the clinical relevance of central
      hypersensitivity, and offer a perspective of treatment of central
      hypersensitivity. METHODS: A review of animal and human studies focusing on the
      mechanisms of postinjury central sensitization, an analysis of psychophysical
      investigations on central hypersensitivity in patients with chronic pain after
      whiplash injury, and a review of possible treatment modalities. RESULTS: Animal
      data show that tissue damage produces plasticity changes at different neuronal
      structures that are responsible for amplification of nociception and exaggerated
      pain responses. Some of these changes are potentially irreversible. There is
      consistent psychophysical evidence for hypersensitivity of the central nervous
      system to sensory stimulation in chronic pain after whiplash injury. Tissue
      damage, detected or not by the available diagnostic methods, is probably the main
      determinant of central hypersensitivity. Psychologic distress could contribute to
      central hypersensitivity via imbalance of supraspinal and descending modulatory
      mechanisms. Although specific treatment strategies are limited, they are largely
      unexplored. IMPLICATIONS: Central hypersensitivity may explain exaggerated pain
      in the presence of minimal nociceptive input arising from minimally damaged
      tissues. This could account for pain and disability in the absence of objective
      signs of tissue damage in patients with whiplash. Central hypersensitivity may
      provide a common neurobiological framework for the integration of peripheral and
      supraspinal mechanisms in the pathophysiology of chronic pain after whiplash.
      Therapy studies are needed.

PMID- 15502693
TI  - Rotavirus: the search for the next generation vaccine.

PMID- 15502694
TI  - Diarrhea morbidity and mortality in Mexican children: impact of rotavirus
      disease.
AB  - AIM: To analyze changes in prevalence and seasonality of diarrhea morbidity and
      mortality and to evaluate the impact of rotavirus disease among Mexican children
      younger than 5 years old. METHODS: Diarrhea surveillance was performed from 1990
      to 2002. Rotavirus testing was performed on stool specimens from 1996 to 2002.
      Data were obtained from different surveillance systems considering a nationwide
      representation in Mexico. Diarrhea morbidity and mortality rates were analyzed
      against time to determine trends or seasonal patterns. RESULTS: Improvement of
      surveillance for all diarrhea episodes denoted an initial morbidity increase from
      1995 to 1999, followed by a decrease by 2002, without any seasonal pattern.
      However, from 1990 to 1995, morbidity for severe diarrhea decreased 63%. From
      1996 to 2002, 62-68% of severe diarrhea episodes occurring during the fall-winter
      season (FWS) were rotavirus-positive compared with 6-12% in the spring-summer
      season (SSS). From 1990 to 2002, diarrhea mortality decreased 84%. Higher
      mortality rates for children younger than 1 year old coincided precisely during
      the FWS, annually. Both severe diarrhea episodes and diarrhea deaths denoted a
      changing seasonal pattern. In 1990-1991, 2 waves of increased diarrhea activity
      occurred. The increase in SSS was much more pronounced than that in FWS. From
      1992 to 1995 for severe diarrhea and from 1993 to 2002 for diarrhea deaths, the
      SSS frequencies subsequently reduced, whereas the FWS peaks remained annually.
      CONCLUSIONS: A significant reduction in morbidity and mortality of severe
      diarrhea has occurred from 1990 and 2002 in Mexican children younger than 5 years
      old. This is a consequence of preventive programs initiated for cholera control
      since 1991, which had greater impact on SSS diarrhea and limited response for FWS
      diarrhea, when rotavirus is mainly present. Currently rotavirus diarrhea requires
      new prevention strategies and specific control measures, such as a specific
      national vaccine program.

PMID- 15502695
TI  - Rotavirus in El Salvador: an outbreak, surveillance and estimates of disease
      burden, 2000-2002.
AB  - BACKGROUND: In December 2000, a large outbreak of gastroenteritis occurred in El
      Salvador that was associated with hospitalizations and deaths among children
      nationwide. Public concern was raised because the etiology was initially unknown
      and enteric control measures seemed ineffective. The outbreak was eventually
      linked to rotavirus, control measures were redirected to improving treatment with
      oral rehydration and surveillance was initiated to characterize the etiologic
      agents of gastroenteritis. METHODS: Demographic and clinical data and fecal
      specimens were collected from a systematic sample of children younger than 5
      years old with acute gastroenteritis. Stools were tested for rotavirus, bacteria
      and parasites. Surveillance results were extrapolated to national data to
      estimate the national burden of rotavirus disease. RESULTS: Surveillance between
      May 2001 and April 2002 demonstrated that rotavirus has winter seasonality, was
      associated with vomiting and dehydration and accounted for an estimated 27% of
      12,083 consultations for diarrhea. Children with rotavirus gastroenteritis were
      younger (median, 9 months) than those with gastroenteritis caused by other agents
      (median, 13 months for bacteria, 16 months for parasites). Extrapolating to
      national data, we estimated the risk of a child experiencing a rotavirus-related
      medical visit, hospitalization and death by the age of 5 years as 1:7, 1:56 and
      1:531, respectively. CONCLUSIONS: The outbreak of gastroenteritis among children
      younger than 5 years of age between December 2000 and February 2001 represented
      an exaggerated rotavirus season. The surveillance activity after the outbreak
      suggests that rotavirus is the most common cause of diarrheal disease in El
      Salvador. Further surveillance could provide a sound basis for improving the
      response to epidemics of gastroenteritis and could provide data needed to decide
      whether rotavirus vaccination should be included in the national program for
      childhood immunizations.

PMID- 15502696
TI  - Epidemiologic and clinical characteristics of rotavirus disease during five years
      of surveillance in Venezuela.
AB  - BACKGROUND: To effectively introduce a rotavirus vaccine in developing countries,
      it is necessary to estimate the burden of rotavirus disease. Therefore we
      examined the epidemiologic and clinical features of rotavirus diarrhea in
      children younger than 5 years of age in Carabobo State and extrapolated these
      results to the rest of Venezuela. METHODS: From January 1, 1998 to December 31,
      2002, we conducted surveillance for rotavirus diarrhea in all children younger
      than 5 years of age at the Ciudad Hospitalaria Dr Enrique Tejera, in Valencia
      (Carabobo). RESULTS: Rotavirus is the major cause of diarrhea in children younger
      than 5 years of age in Venezuela, accounting for one-fourth (23%) of all episodes
      of diarrhea requiring medical treatment and one-third (33%) of those requiring
      hospitalization. Rotavirus diarrhea was responsible for 3% of all
      hospitalizations and 2% of all medical visits. In Valencia, rotavirus had a
      marked seasonal peak during the dry and cold months of the year. Rotavirus was
      most frequent in children 3-23 months of age, and 61% of the cases occurred by
      the age of 1 year. In addition, rotavirus diarrhea was more severe in younger
      children. Overall, by the age of 5 years, 1 child in 72 will be hospitalized and
      1 in 24 will visit the clinic for rotavirus disease. In Venezuela, we estimated
      that each year, 118,000 children experience rotavirus illness requiring medical
      care and 39,000 children require hospitalization. CONCLUSIONS: This study
      confirms the significant impact of rotavirus disease in Venezuela. Rotavirus
      vaccines currently in development could diminish the morbidity associated with
      this common cause of childhood diarrheal disease.

PMID- 15502697
TI  - Rotavirus strain surveillance in Latin America: a review of the last nine years.
AB  - BACKGROUND: Latin America will likely be the first area in the developing world
      where rotavirus vaccine will be introduced into the routine childhood
      immunization schedule. In anticipation of that goal, we reviewed the distribution
      of group A rotavirus genotypes in Latin America to understand the diversity of
      strains to be targeted by vaccines and to identify novel strains that may pose
      challenges for vaccines. METHODS: We reviewed studies characterizing rotavirus
      strains in Latin America (published in English since 1995) that used molecular
      methods to type genes encoding the G and P outer capsid proteins, VP7 and VP4,
      and that reported data on >50 specimens. RESULTS: Fifteen studies from 5
      countries met our criteria. In total, 1989 samples were characterized; 12% (233)
      were mixed rotavirus infections with more than 1 strain, and 20% (402) were not
      fully typable. Of the remaining 1354 samples that were fully typed, 83%
      represented the 4 common strains: P[8],G1 (40%); P[4],G2 (30%); P[8],G3 (6%);
      P[8],G4 (7%). The unusual strains provide interesting insights into virus
      evolution: some strains (G5) were regionally common; the emerging G9 strains were
      widely distributed; many animal-human reassortants were present; and some common
      serotypes (G3 and G4) were of animal origin. Also an unusual G12 serotype was
      recently detected in Argentina. CONCLUSIONS: The common rotavirus serotypes
      should remain the prime targets for vaccine development. However, the changing
      profile of rare strains, animal-human reassortants and nontypable strains suggest
      that rotavirus is constantly evolving. Laboratory surveillance is needed to
      monitor rotavirus strains now in circulation and to detect those that might
      escape the immunity induced by vaccines or represent vaccine strains entering the
      environment.

PMID- 15502698
TI  - Natural rotavirus infection is not associated to intussusception in Mexican
      children.
AB  - AIMS: To determine whether natural rotavirus infection or infection by another
      enteropathogen is associated to intussusception (IS); and to describe the
      seasonality of IS compared with severe diarrhea (SD) and rotavirus SD in Mexican
      children. METHODS: A prospective, observational, multicenter and case-control
      study was conducted in Mexico City from December 1999 to February 2001. Cases
      were children younger than 1 year old hospitalized for IS; diagnosis was made by
      clinical features, radiologic and/or surgery findings. Controls were children
      younger than 1 year old hospitalized for another disease than a gastrointestinal
      illness (NGI). Cases and controls were paired by age and date of admission (+/-3
      months; for both), in a 1:2 ratio. A surveillance of IS cases, SD and rotavirus
      SD episodes was conducted during the study period. Stool samples collected soon
      after IS resolution or at admission were tested for rotavirus, adenovirus,
      astrovirus, bacteria and parasites. RESULTS: Thirty cases of IS and 60 controls
      with NGI were studied. Rotavirus was not detected in any case of IS. Adenovirus
      (17%) was the only enteropathogen detected in IS. Rotavirus (8%), adenovirus
      (2%), astrovirus (2%) and bacteria (2%) were detected in NGI. Rotavirus infection
      was not associated with IS (odds ratio, 0; 95% confidence interval, 0-2.9),
      whereas adenovirus infection was strongly associated as risk factor for IS (odds
      ratio undefined; P = 0.003), compared with NGI. Seasonal variation in admissions
      for IS was small, whereas admissions for SD and rotavirus SD showed a marked
      seasonal increase during fall-winter. CONCLUSIONS: In Mexican children, rotavirus
      infection was not associated to IS; whereas a significant association was
      observed between adenovirus and IS. Also there was no increase in IS cases during
      the sharply defined fall-winter rotavirus outbreak. Observations from this
      controlled study suggest that natural rotavirus infection is not a risk factor
      for IS. This information may have implications for development of a safer and
      effective rotavirus vaccine.

PMID- 15502699
TI  - A rotavirus vaccine for prophylaxis of infants against rotavirus gastroenteritis.
AB  - The need for safe and effective vaccines to reduce morbidity and mortality caused
      by rotavirus gastroenteritis in children is well-known. A live attenuated
      monovalent rotavirus vaccine (Rotarix) containing human rotavirus strain RIX4414
      of G1P1A P[8] specificity is being developed to meet the global need. An overview
      of RIX4414 trials in developed and developing settings is presented for 3
      selected trials conducted in Finland (pilot study), Latin America (Brazil, Mexico
      and Venezuela) and Singapore involving 5024 infants. The vaccine was well
      tolerated, with no increase in any solicited symptoms as compared with the
      placebo. After 2 doses, 61-91% of vaccinated infants developed rotavirus-specific
      IgA antibodies. There was no interference with immunogenicity of coadministered
      routine pediatric vaccines. Rotarix significantly reduced rotavirus
      gastroenteritis episodes and rotavirus-related hospitalizations in vaccinated
      infants compared with placebo recipients (P < 0.05). Vaccine efficacy was
      observed against severe rotavirus gastroenteritis caused by G1 and non-G1 types
      including the emerging G9 type (P < 0.05) in Latin America. These results show
      prospects for widespread use of Rotarix to reduce rotavirus disease burden and
      warrant continued worldwide evaluation.

PMID- 15502700
TI  - Immune response, accommodation, and tolerance to transplantation carbohydrate
      antigens.
AB  - The carbohydrate antigens, blood groups A and B, and the alpha-gal epitope
      (Galalpha1-3Gal) are major risk factors in transplantation. Transplantation
      across ABO barriers may result in rejection by elicited anti-blood group
      antibodies, accommodation where elicited anti-blood group antibodies do not
      reject the graft, or tolerance where no anti-blood group antibodies are produced
      and the graft is not rejected. alpha1,3Galactosyltransferase knockout mice that
      lack alpha-gal epitopes but produce the anti-Gal antibody serve as a model for
      studying these immune responses. Knockout mice underwent transplantation
      heterotopically with wild-type mouse heart expressing alpha-gal epitopes and
      subsequently received lymphocytes including naive and memory anti-Gal B cells.
      The type of elicited immune response was found to be associated with the period
      that anti-Gal B cells were exposed to alpha-gal epitopes of the graft in the
      absence of T-cell help. Immediate T-cell help induced production of cytolytic
      anti-Gal antibodies that reject the graft, whereas delayed T-cell help induced
      production of accommodating anti-Gal antibodies. In the absence of T-cell help
      for prolonged periods, anti-Gal B cells exposed to alpha-gal epitopes were
      deleted, resulting in tolerance. Similar variations in the extent of T-cell help
      may determine the B-cell response to incompatible A or B antigens. The
      experimental model further suggests that active tolerance induction before
      transplantation may be achieved by gene therapy with autologous bone marrow cells
      or autologous lymphocytes manipulated to express the incompatible transplantation
      carbohydrate antigen by introduction of the corresponding glycosyltransferase
      gene into these cells.

PMID- 15502701
TI  - Ethical issues and xenotransplantation.

PMID- 15502702
TI  - Position paper of the Ethics Committee of the International Xenotransplantation
      Association.
AB  - Xenotransplantation (XTx) provides a potential solution to the shortage of human
      organs and tissues, and has several advantages over other possible solutions to
      this problem. However, a number of scientific and ethical barriers exist, and
      need to be addressed in order to advance the field of XTx in a manner that
      optimizes its potential to benefit society and minimizes its risk. Some of the
      most pressing ethical issues are discussed, and the position of the Ethics
      Committee of the International Xenotransplantation Association is presented.

PMID- 15502703
TI  - The road to clinical xenotransplantation: a worthwhile journey.
AB  - Xenotransplantation carries numerous ethical dilemmas. In the Position Paper of
      the Ethics Committee of the International Xenotransplantation Association, Sykes
      et al. diagram important ethics issues including respect for clinical subjects
      characterized by proper informed consent, and beneficence to the patient and the
      community at large, highlighting the possible risk of porcine endogenous
      retroviruses and xenotourism. We propose optimizing informed consent to take into
      account the psychological, scientific, and ethical nuances of
      xenotransplantation. Moreover, regulation of xenotourism should mirror
      established U.S. guidelines for visitors with communicable diseases, thereby not
      limiting the rights of xenotransplant recipients.

PMID- 15502704
TI  - Commentary: On the position paper of the Ethics Committee of the International
      Xenotransplantation Association.
AB  - The Position Paper of the Ethics Committee of the International
      Xenotransplantation Association has argued in favor of moving forward with
      xenotransplantation trials but only under highly controlled conditions, including
      consideration of ethical concerns. Although stressing the importance of ethics,
      this recommendation to proceed was ultimately based on a risk-benefit calculus.
      There are two areas that need to be addressed more fully: 1) the nature of the
      decision to be made; and 2) the nature and extent of participation by publics as
      part of this political process.

PMID- 15502705
TI  - Public consultation on xenotransplantation.
AB  - Although xenotransplantation could potentially benefit individuals with organ
      failure, this new technology is both controversial and potentially risky not only
      to recipients and their close contacts but also to society as a whole. The
      Canadian government wanted the public to have input into the decision of whether
      to pursue this new treatment. Therefore, Health Canada hired the Canadian Public
      Health Association to design and perform an arm's length public consultation;
      this program resulted in some high-profile negative recommendations. I offer an
      alternative analysis of the data collected during the consultation, which results
      in different conclusions.

PMID- 15502706
TI  - Molecular approaches to the side effects of immunosuppressive drugs.

PMID- 15502707
TI  - Exogenous alpha-1-acid glycoprotein protects against renal ischemia-reperfusion
      injury by inhibition of inflammation and apoptosis.
AB  - BACKGROUND: Although ischemia-reperfusion (I/R) injury represents a major problem
      in posttransplant organ failure, effective treatment is not available. The acute
      phase protein alpha-1-acid glycoprotein (AGP) has been shown to be protective
      against experimental I/R injury. The effects of AGP are thought to be mediated by
      fucose groups expressed on the AGP protein inhibiting neutrophil infiltration.
      However, the precise mechanism of protection remains to be established. We
      therefore studied the effects of exogenous human AGP (hAGP) in a mouse model of
      ischemic acute renal failure. METHODS: Mice were subjected to renal I/R and
      treated with hAGP, fucose-depleted hAGP, or control treated. Also, transgenic
      mice over-expressing rat AGP or wild-type controls were subjected to renal I/R.
      RESULTS: Treatment was with hAGP as well as fucose-depleted hAGP protected mice
      against I/R-induced acute renal failure. Surprisingly, AGP-over-expressing mice
      were not protected against I/R injury. Both natural and fucose-depleted hAGP
      inhibited the activation of the complement system, as determined by renal C3
      deposition and influx of neutrophils measured by immunohistochemistry and
      myeloperoxidase-enzyme-linked immunoadsorbent assay. Tubular epithelial cell
      structure (actin cytoskeleton) and cell-cell interaction (tight-junction
      architecture) were completely preserved in AGP-treated mice. Also, epithelial
      caspase activation and apoptotic DNA cleavage were prevented by AGP treatment.
      CONCLUSIONS: Both natural and fucose-depleted hAGP protect against renal I/R
      injury by preservation of tubular epithelial structure and inhibition of
      apoptosis and subsequent inflammation. Therefore, hAGP can be regarded as a
      potential new therapeutic intervention in the treatment of acute renal failure,
      as seen after transplantation of ischemically injured kidneys.

PMID- 15502708
TI  - Evidence for tissue-directed immune responses: analysis of CD4- and CD8-dependent
      alloimmunity.
AB  - BACKGROUND: Transplant rejection has generally been considered a CD4 T-cell
      dependent immune process. CD4-independent, CD8 T-cell rejection pathways have
      recently gained attention because of their relative resistance to
      immunosuppression. In the current study, the role of the allograft tissue in
      activation of these distinct pathways was examined by comparing host-immune
      responses with allogeneic pancreatic islets or hepatocytes transplanted across
      the same genetic disparity. METHODS: To compare activation of CD4-dependent
      versus CD8-dependent alloimmunity, islets or hepatocytes retrieved from FVB/N (H
      2) mice were transplanted into CD8 or CD4 T-cell-reconstituted severe combined
      immunodeficiency mice, CD4 or CD8 knockout (KO) mice, and anti-CD4 monoclonal
      antibody (mAb) or anti-CD8 mAb treated C57BL/6 mice (all H-2). The ability to
      immunomodulate CD4-dependent allograft rejection (in CD8 KO mice) was examined in
      the context of several mechanistically distinct immunotherapeutic strategies,
      including anti-CD4 mAb, donor-specific transfusion and anti-CD154 mAb, and anti
      lymphocyte function-associated antigen-1 mAb. RESULTS: The studies demonstrate
      that, whereas hepatocytes evoke alloreactive CD4-dependent and (CD4-independent)
      CD8 T-cell immune responses, allogeneic islets only activate CD4-dependent immune
      pathways. CD4-dependent host-immune responses initiated by pancreatic islet
      allografts were readily suppressed by a variety of short-term immunotherapies,
      whereas hepatocyte-initiated CD4-dependent alloimmune responses were not.
      CONCLUSIONS: These results demonstrate that immune characteristics of the
      specific allograft tissue uniquely influence the pattern of host immune responses
      such that the propensity to activate CD4- or CD8-dependent alloimmune responses
      can be distinguished. Furthermore, CD4-dependent immune responses activated by
      different tissues from the same donor strain are distinguished by their
      susceptibility to specific immunotherapy.

PMID- 15502709
TI  - Immunomodulatory effects of combination of pooled human gammaglobulin and
      rapamycin on cell proliferation and apoptosis in the mixed lymphocyte reaction.
AB  - BACKGROUND: Multidrug immunosuppressive regimens benefit transplant recipients,
      reducing side effects and creating synergy between medications with different
      mechanisms of action. We have shown that pooled human gammaglobulin (intravenous
      immunoglobulin [IVIG]) inhibits the mixed lymphocyte reaction (MLR) and induces
      apoptosis primarily in B cells. Rapamycin (RAPA), a potent macrolide
      immunosuppressant, inhibits B- and T-cell proliferation through G1 cell-cycle
      blockade and purportedly induces apoptosis. Here we examined the possible
      synergistic effects of IVIG and RAPA on cell proliferation and apoptosis
      induction in the MLR. METHODS: MLR was performed with IVIG (0.2-5 mg/mL), RAPA
      (0.02-40 ng/mL), alone or in combination. Cell proliferation was detected by H
      thymidine incorporation, and apoptosis by Annexin V and terminal deoxynucleotide
      transferase-mediated dUTP nick-end labeling flow cytometry. RESULTS: IVIG or RAPA
      inhibited cell proliferation in a dose-dependent manner. RAPA (0.02-40 ng/mL) in
      combination with IVIG (5 mg/mL) significantly augmented the inhibition compared
      with RAPA alone (70% vs. 34% at 0.2 ng/mL; 90% vs. 76% at 2 ng/mL). Apoptosis was
      significantly higher in IVIG-treated (5 mg/mL) CD19+ cells and less so in CD3+
      cells. However, RAPA (0.2-40 ng/mL) neither induced apoptosis nor altered
      apoptosis induced by IVIG. CONCLUSIONS: Combined RAPA and IVIG at subtherapeutic
      concentrations inhibits cell proliferation in the MLR. RAPA neither induces
      apoptosis nor augments apoptosis induced by IVIG in the MLR. Lower-concentration
      RAPA (0.2-2 ng/mL) in combination with IVIG (5 mg/mL) versus therapeutic levels
      (2-50 ng/mL and 10-40 mg/mL, respectively) could represent an effective
      immunomodulatory drug combination.

PMID- 15502710
TI  - Urinary matrix metalloproteinases and their endogenous inhibitors predict hepatic
      regeneration after murine partial hepatectomy.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) play a key role in extracellular
      matrix remodeling events associated with hepatic regeneration after partial
      hepatectomy. We therefore hypothesized that urinary MMPs and their endogenous
      tissue inhibitors of matrix metalloproteinases (TIMPs) might also provide
      important information regarding initiation and progression of liver regeneration.
      METHODS: Groups of 20 mice underwent sham operations, two-thirds hepatectomy, or
      treatment with the angiogenesis inhibitor, AGM-1470,O-chloroacetyl-carbamoyl
      fumagillol (TNP-470), after two-thirds hepatectomy to prevent hepatic
      regeneration. Urine was collected preoperatively and for 24 days after surgery
      and tested for MMP-2, MMP-9, TIMP-1, and TIMP-2 using substrate gel
      electrophoresis (zymography) and Western blot analysis. RESULTS: During hepatic
      regeneration, MMP-9 was detected in the urine at significantly lower levels on
      postoperative day 8 when the liver returned to its preoperative mass. In
      contrast, urine from mice whose livers were inhibited from regenerating (TNP
      treated groups) contained increased levels of the gelatinases MMP-2 and MMP-9.
      The MMP inhibitors, TIMP-1 and TIMP-2, were significantly reduced in the urine of
      mice with normally regenerating livers but were increased in the urine of mice
      treated with TNP-470 on day 8. CONCLUSIONS: We demonstrate that (1) urinary MMPs
      and their cognate inhibitors, the TIMPs, can be detected in the urine of mice
      undergoing partial hepatectomy, (2) the presence of these remodeling proteins in
      the urine may predict the progressive return of the partially resected liver to
      its preoperative mass, and (3) analysis of urinary MMPs and TIMPs may someday
      provide a noninvasive means of monitoring the status of patients undergoing
      hepatic resection and transplantation.

PMID- 15502711
TI  - cDNA microarray analysis reveals new candidate genes possibly linked to side
      effects under mycophenolate mofetil therapy.
AB  - BACKGROUND: Mycophenolate mofetil (MMF) the prodrug of mycophenolic acid is
      usually well tolerated. Side effects such as anemia and diarrhea occur in
      approximately 10%-15% of patients. The aim of this study was to examine in a rat
      model the effect of MMF on gene expression in liver and gut to identify target
      genes with possible relevance to MMF side effects. METHODS: Twelve Wistar rats
      were treated with 40 mg/kg body weight MMF orally for 21 days. Controls (n=9)
      received vehicle only. RNA was extracted from liver, jejunum, ileum, and colon
      and transcribed into cDNA. Regulated genes were identified in liver by DNA
      microarray experiments. Gene regulation was verified in liver and gut using
      quantitative real-time PCR on the LightCycler instrument. Transcription
      elongation factor 2 served as reference gene. RESULTS: Microarray analysis
      revealed that major alpha-hemoglobin, polymeric immunoglobulin receptor,
      catalase, and CCAAT/enhancer protein alpha gene expression were down-regulated in
      livers of MMF-treated rats 10-, 5.5-, 4-, and 5-fold, respectively. These
      findings could be confirmed through quantitative real-time PCR analysis of gene
      expression in liver, ileum, jejunum, and colon. CONCLUSION: Using microarray
      analysis and a rat model four candidate genes which may be functionally linked to
      side effects (major alpha-hemoglobin-->anaemia; polymeric immunoglobulin receptor
      ->protection of mucosa; catalase and CCAAT/enhancer protein alpha-->oxidative
      stress) of MMF therapy were identified.

PMID- 15502712
TI  - Myocardial protective effect of human recombinant hepatocyte growth factor for
      prolonged heart graft preservation in rats.
AB  - BACKGROUND: In heart transplantation, myocardial apoptosis during hypothermic
      storage contributes to graft dysfunction. On the other hand, hepatocyte growth
      factor (HGF) has been reported to be an antiapoptotic factor in the heart.
      Therefore, we assessed whether the administration of recombinant human HGF (rh
      HGF) prevents apoptosis in the prolonged preserved myocardium, resulting in an
      improvement in the cardiac function of the graft. METHODS: Isolated rat hearts
      were subjected to 4 hr (group A), 6 hr (group B), and 8 hr (group C: without rh
      HGF vs. group D: with 100 microg of rh-HGF) of hypothermic storage followed by 60
      min of normothermic reperfusion (n=5 in each group). RESULTS: Compared with non
      HGF-treated hearts (group C), HGF-treated hearts (group D) showed a significantly
      higher recovery rate of left ventricular developed pressure (38+/-5% vs. 58+/-6%,
      P<0.01) and maximum dp/dt (53+/-7% vs. 74+/-4%, P<0.01) and a lower rate of TUNEL
      positive cardiomyocytes (7.8+/-6.0% vs. 25.3+/-8.9%, P<0.05) after 60 min of
      reperfusion. Western blot analysis revealed that c-Met/HGF receptor expression
      was stronger in the HGF-treated myocardium than in the non-HGF-treated myocardium
      after 8 hr of storage and was associated with a weaker expression of caspase-3
      and a stronger expression of Bcl-xL after 60 min of reperfusion. CONCLUSION: The
      administration of rh-HGF before storage improved cardiac function after prolonged
      myocardial preservation by preventing apoptosis through the c-Met/HGF receptor.
      Thus, the addition of rh-HGF in the storage solution may be a promising strategy
      for prolonged heart graft preservation.

PMID- 15502713
TI  - Effects of portal vein arterialization on regeneration and morphology in liver
      transplantation: investigations using the rat model.
AB  - BACKGROUND: Portal vein arterialization (PVA) has been proposed as a technical
      variant in liver transplantation in the case of non-recanalizable thrombosis. The
      present study investigates the effects of the arterialized portal vein on the
      function, morphology, and regenerative behavior of the liver. METHODS: Different
      PVA techniques, including orthotopic liver transplantation, were used in a rat
      model. Portal blood flow was measured using a ultrasonic flowmeter. The
      regeneration capacity was determined on the basis of the increase of liver weight
      and the proliferating cell nuclear antigen index. The amount of hydroxyproline
      and the transcript levels of procollagen I were measured to determine the degree
      of fibrosis. The extracellular matrix was visualized with Picro-Sirius staining.
      RESULTS: The measurements obtained with an ultrasonic probe revealed a
      significant increase in portal blood flow after PVA. The regeneration capacity in
      the groups after PVA with no flow reduction was comparable to that of the
      control. Liver transplantation and PVA with no flow reduction was followed by a
      significant increase (four- to sixfold) in the amount of hydroxyproline and the
      level of the mRNA for procollagen I. In the Picro-Sirius staining, periportal and
      perivascular fibrosis with incipient formation of septa was seen. After reduction
      of the portal blood flow, these effects were significantly less pronounced.
      CONCLUSIONS: These operative techniques represent an excellent small animal model
      for studying the mechanism of liver regeneration and the genesis of fibrosis in
      liver and vessel tissue. The presenting findings indicate that the negative
      effects of "overarterialization" may be largely avoided by reducing portal blood
      flow. This implies that permanent PVA in clinical liver transplantation should be
      performed only in conjunction with a down-regulation of portal flow.

PMID- 15502714
TI  - Superoxide dismutase mimetic m40401 reduces ischemia-reperfusion injury and graft
      coronary artery disease in rodent cardiac allografts.
AB  - BACKGROUND: The oxidative stress associated with ischemia-reperfusion (I/R) of
      cardiac allografts leads to production of injurious cytokines and expression of
      proinflammatory adhesion molecules. This is one of the most important alloantigen
      independent factors associated with graft coronary artery disease (GCAD). M40401
      is a newly developed cell permeable superoxide dismutase mimetic, which has been
      shown to scavenge superoxide anion with highly specific and enhanced catalytic
      activity. We hypothesized that M40401 would exert a protective effect in I/R
      injury of cardiac allografts and ameliorate the progression of GCAD. METHODS:
      Recipient ACI rats were pretreated with M40401 or vehicle control. PVG donor
      hearts were heterotopically transplanted into the abdomen of ACI recipients.
      Cardiac allografts were analyzed for adhesion molecule mRNA expression and tumor
      necrosis factor-alpha expression after 4 hr of reperfusion. Neutrophil
      infiltration was detected by myeloperoxidase activity. Intercellular adhesion
      molecule-1, vascular cell adhesion molecule-1, and endothelial leukocyte adhesion
      molecule-1 mRNA were detected by reverse-transcriptase polymerase chain reaction.
      Immunohistochemical analysis of adhesion molecule expression was also performed.
      Additional grafts were procured 90 days after transplantation and assessed for
      the development of GCAD by computer-assisted image analysis. RESULTS: In the
      M40401-treated group, adhesion molecule expression was significantly less than in
      the vehicle control group. Treated grafts also had lower myeloperoxidase activity
      and tumor necrosis factor-alpha concentration compared with controls. Neointimal
      proliferation and intima to media ratios in M40401-treated allografts were
      significantly decreased compared with controls. CONCLUSIONS: Selective removal of
      superoxide anion by M40401 results in inhibition of I/R injury. Furthermore,
      M40401 treatment decreases the development of oxidative stress-associated GCAD.
      This treatment strategy may have broad cardioprotective applications for all
      cardiac operations in addition to cardiac transplantation.

PMID- 15502715
TI  - Superior survival and proliferation after transplantation of myoblasts obtained
      from adult mice compared with neonatal mice.
AB  - BACKGROUND: Myoblast transfer therapy (MTT) is a strategy designed to compensate
      for the defective gene in myopathies such as Duchenne muscular dystrophy (DMD).
      Experimental MTT in the mdx mouse (an animal model of DMD) has used donor
      myoblasts derived from mice of various ages; however, to date, there has been no
      direct quantitative comparison between the efficacy of MTT using myoblasts
      isolated from adult and neonate donor muscle. METHODS: Donor normal male
      myoblasts were injected into Tibialis Anterior muscles of dystrophic female host
      mice and the survival and proliferation of male myoblasts quantitated using Y
      chromosome specific real-time quantitative polymerase chain reaction. The
      survival of late preplate (PP6) myoblasts derived from neonatal (3-5 days old) or
      adult (6-8 weeks old) donor mice after MTT were compared. The influence of the
      number of tissue culture passages, on survival post-MTT, was also evaluated for
      both types of myoblasts. RESULTS: Surprisingly, superior transplantation
      efficiency was observed for adult-derived compared with neonatal myoblasts (both
      early and late passage). Extended expansion (>17 passages) in tissue culture
      resulted in inferior survival and proliferation of both adult and neonatal
      myoblasts; however, proliferation of early passage myoblasts (both adult and
      neonate) was evident between 3 weeks and 3 months. CONCLUSIONS: Myoblasts derived
      from neonatal mice were inferior for transplantation, and early passage donor
      myoblasts from adult mice are recommended for MTT in this model.

PMID- 15502716
TI  - Plasma kinetics of a cholesterol-rich microemulsion in patients submitted to
      heart transplantation.
AB  - BACKGROUND: Development of coronary graft disease is currently the main cause of
      late heart-transplantation (HT) failure. HT patients frequently show
      hypercholesterolemia as well as alterations in chylomicron metabolism. These
      postHT changes may be important in coronary graft disease development. To clarify
      whether hypercholesterolemia is caused by decreased low-density lipoprotein (LDL)
      removal from the plasma, we studied the plasma kinetics of a cholesterol-rich
      emulsion that binds to LDL receptor. METHODS: We studied 13 HT patients and 13
      healthy normolipidemic subjects paired for sex, age, and body mass index. An
      emulsion labeled with C-cholesteryl oleate was injected intravenously, and blood
      samples were collected in predetermined intervals (5 minutes, 1, 2, 4, 6, and 8
      hours) to determine the radioactivity decay curves and to calculate the
      fractional clearance rates (FCR). RESULTS: The plasma level of total cholesterol,
      LDL cholesterol, high-density lipoprotein cholesterol, and apo B were greater in
      HT group than in the control group (P<0.005). FCR C-cholesteryl oleate was
      smaller in HT patients when compared with the control group (P=0.02). CONCLUSION:
      The results showed that HT patients have a deficiency in the mechanisms of LDL
      removal from the plasma, as tested by the cholesterol-rich emulsion, and this may
      be important in the development of coronary graft disease.

PMID- 15502717
TI  - Influence of CYP3A5 and MDR1 (ABCB1) polymorphisms on the pharmacokinetics of
      tacrolimus in renal transplant recipients.
AB  - BACKGROUND: A body-weight-based dose of tacrolimus often results in marked
      individual diversity of blood drug concentration. Tacrolimus is a substrate for
      cytochrome P450 (CYP) 3A5 and p-glycoprotein encoded by CYP3A5 and MDR1 (ABCB1),
      respectively, having multiple single nucleotide polymorphisms. In this study, we
      genotyped CYP3A5 A6986G, MDR1 G2677(A/T), and C3435T polymorphisms and
      investigated the association between these polymorphisms and the pharmacokinetics
      of tacrolimus in renal transplant recipients. METHODS: Thirty consecutive
      recipients were enrolled in this study. The pharmacokinetics of tacrolimus was
      analyzed on day 28 after transplant, when the daily dose was adjusted to the
      target trough level of 10-15 ng/mL. The polymerase chain reaction-restriction
      fragment length polymorphism and direct sequence method were used for genotyping
      the CYP3A5 and MDR1 polymorphisms, respectively. RESULTS: The single tacrolimus
      dose per body weight was significantly higher in CYP3A5 *1 carriers than CYP3A5
      *3/*3 carriers (0.143+/-0.050 vs. 0.078+/-0.031 mg/kg, P<0.001). The dose
      adjusted trough level and the area under the concentration-time curve (AUC0-12)
      were significantly lower in CYP3A5 *1 carriers than CYP3A5 *3/*3 carriers
      (0.040+/-0.014 vs. 0.057+/-0.024 ng/mL/mg/kg, P=0.015 and 0.583+/-0.162 vs.
      0.899+/-0.319 ng.hr/mL/mg/kg, P=0.004), respectively. The MDR1 polymorphism was
      not associated with any pharmacokinetic parameters. CONCLUSIONS: Kidney
      transplant recipients with the CYP3A5 *1 allele required a higher daily
      tacrolimus dose compared with those with the CYP3A5 *3/*3 genotype to maintain
      both the target trough level and AUC0-12, suggesting that this polymorphism is
      useful for determining the appropriate dose of tacrolimus.

PMID- 15502718
TI  - Technical failures after pancreas transplants: why grafts fail and the risk
      factors--a multivariate analysis.
AB  - BACKGROUND: Technical failure (TF) rates remain high after pancreas transplants;
      while rates have decreased over the last decade, more than 10% of all pancreas
      grafts continue to be lost due to technical reasons. We performed a multivariate
      analysis to determine causes and risk factors for TF of pancreas grafts. RESULTS:
      Between 1994 and 2003, 937 pancreas transplants were performed at our center in
      the following transplant categories: simultaneous pancreas-kidney (SPK) (n=327),
      pancreas after kidney (PAK) (n=399), and pancreas transplant alone (PTA) (n=211).
      Of these, 123 (13.1%) grafts were lost due to technical reasons (thrombosis,
      leaks, infections). TF rates were higher for SPK (15.3%) versus PAK (12.2%) or
      PTA (11.4%), though this was not statistically significant. Thrombosis accounted
      for 52.0% of all TFs. Other causes were infections (18.7%), pancreatitis (20.3%),
      leaks (6.5%), and bleeding (2.4%). Thrombosis was the most common cause for TF in
      all three transplant categories. By multivariate analysis, the following were
      significant risk factors for TF of the graft: recipient body mass index (BMI) >30
      kg/m (relative risk [RR]=2.42, P=0.0003), preservation time >24 hr (1.87,
      P=0.04), cause of donor death other than trauma (RR=1.58, P=0.04), enteric versus
      bladder drainage (1.68, P=0.06), and donor BMI >30 kg/m (1.66, P=0.06). Not
      significant were donor or recipient age, a retransplant, and the category of
      transplant. CONCLUSIONS: TFs remain significant after pancreas transplants. In
      SPK recipients, TF represents the most common cause of pancreas graft loss. For
      isolated pancreas transplants, TF is second only to rejection as a cause of graft
      loss. Increased preservation times and donor or recipient obesity seem to be risk
      factors. Minimizing these risks factors would be important to try to decrease TF.

PMID- 15502719
TI  - Noradrenaline use in the human donor and relationship with load-independent right
      ventricular contractility.
AB  - BACKGROUND: Experimental and clinical studies suggest that brain death (BD)
      associated cardiac dysfunction is related to the neurohormonal storm and
      subsequent exposure to intravenous catecholamines. We aimed to describe the
      relationship between empirical noradrenaline treatment and donor heart function,
      described for the first time with load-independent indices of right ventricular
      contractility. METHODS: Twenty-seven BD patients were divided in three groups
      based on noradrenaline at time of offer, started by the donor hospital: group
      1=no noradrenaline (n=11); group 2=low dose (n=8); group 3=high dose (n=8). After
      protocol-guided optimization by our retrieval team using a Swan-Ganz catheter,
      pressure-volume data were obtained from the right ventricle. Ten patients
      undergoing coronary revascularization served as controls. RESULTS: Twenty hearts
      were transplanted, seven of them as heart and lung blocks. Right ventricular end
      systolic elastance (E(es)) was lower in BD donors compared with controls (mean
      0.28 vs. 0.46 mm Hg/mL, P< or =0.01). There was no difference in terms of Swan
      Ganz derived data between the BD subgroups, but E(es) was lower in groups 2 and 3
      (P=0.04). Eight patients died within a year (four from graft failure), and they
      had a donor heart E(es) significantly lower than that of survivors (mean 0.20 vs.
      0.33 mm Hg/mL, P=0.01). CONCLUSION: Hearts from BD donors have subclinical right
      ventricular impairment in contractility. E(es), a load-independent measure of
      contractile function, seems to be inversely correlated with empirical use of
      noradrenaline in the donor and with recipient survival at 1 year. This has
      implications for refining donor selection and management.

PMID- 15502720
TI  - Cyclosporine minimization and cost reduction in renal transplant recipients
      receiving a C2-monitored, cyclosporine-based quadruple immunosuppressive regimen.
AB  - BACKGROUND: Targeting 2-hr postdose cyclosporine (C2) levels to 1,000 to 1,700
      mg/dL during the first 6 months after renal transplantation is recommended for
      triple immunosuppressive regimens. This trial determines whether lower C2 levels
      could be targeted safely in de novo kidney transplant recipients under a
      quadruple regimen compared with a similar cohort monitored with trough (C0)
      levels. METHODS: This single-center, sequential, cohort-designed trial included
      patients who received Thymoglobulin, corticosteroids, an antimetabolite, and
      cyclosporine monitored by C2 (n=50) or C0 (n=50). Cyclosporine was tapered to
      maintain the C2 between 1,000 and 1,200 ng/mL months 0 to 3 and between 600 and
      1,000 ng/mL thereafter and C0 between 250 and 350 ng/mL months 0 to 3 and between
      100 and 250 ng/mL thereafter. RESULTS: Baseline patient and donor characteristics
      were similar. There were no differences in graft survival (100% C2 vs. 100% C0),
      acute rejection (4% C2 vs. 6% C0), allograft function, or adverse events at 6
      months. C2 levels were lower than the suggested guidelines throughout the study
      (33% lower at 1 month and 48% lower at 6 months). Lower cyclosporine doses were
      achieved in the C2 arm compared with the C0 arm by 1 month and were sustained
      throughout the trial, which translated into an average cyclosporine cost savings
      of USD $773 in the C2 arm during the 6-month period (P<0.001). CONCLUSION: With a
      quadruple immunosuppressive regimen and lower C2 targets than recommended for
      triple therapy, safe and effective cyclosporine minimization was achieved. Lower
      cyclosporine doses were achieved in C2-monitored patients compared with C0
      monitored patients, translating into lower immunosuppressive costs.

PMID- 15502721
TI  - Calcium channel blockade and preservation of renal graft function in cyclosporine
      treated recipients: a prospective randomized placebo-controlled 2-year study.
AB  - BACKGROUND: Studies have provided conflicting results as to the protective role
      of calcium channel blockers (CCB) in cyclosporine-treated patients with regard to
      blood pressure control and preservation of renal graft function. Lacidipine is a
      dihydropyridine CCB that possesses antioxidative, anti-atherosclerotic, and anti
      adhesion properties and was shown to prevent cyclosporine-induced nephrotoxicity
      in a rat model. METHODS: We conducted a multicenter prospective, randomized,
      placebo-controlled study in 131 de novo recipients of a cadaveric renal allograft
      on cyclosporine therapy. The aim of this 2-year study was to assess the effects
      of lacidipine on graft function (plasma iohexol clearance), renal plasma flow,
      anastomotic arterial blood flow, deterioration of renal function, blood pressure,
      acute rejection, and hospitalization rate. RESULTS: A total of 118 recipients
      were available for intention-to-treat analysis on efficacy (lacidipine: n=59;
      placebo: n=59). Graft function assessed by serum creatinine concentration and
      glomerular filtration rate measured as plasma iohexol clearance, was persistently
      better in lacidipine-treated patients from 1 year onwards (respectively, P<0.01
      and P<0.05). Renal plasma flow and anastomotic blood flow were not significantly
      higher in lacidipine-treated patients. Three patients on lacidipine therapy and
      four on placebo experienced treatment failure defined as an increase in serum
      creatinine from baseline of more than 60% (log-rank test: P=0.57). Study groups
      did not differ in acute rejection rate, trough blood cyclosporine concentrations,
      blood pressure, number of antihypertensive drugs, hospitalization rate, and
      adverse event rate. CONCLUSIONS: The use of calcium channel blockers in
      cyclosporine-treated renal recipients results in a significantly better allograft
      function at 2 years and this effect is independent of blood pressure lowering.

PMID- 15502722
TI  - Two-dose daclizumab induction therapy in 209 liver transplants: a single-center
      analysis.
AB  - BACKGROUND: Patient and graft survival after liver transplantation are adversely
      affected by early posttransplant renal dysfunction. Therefore, our
      immunosuppressive strategies should be as "renal sparing" as possible. This is
      the largest published series to date using daclizumab induction therapy in a
      renal-sparing regimen. METHODS: This is a retrospective, nonrandomized study
      comparing 209 adult liver transplants with daclizumab induction to 115
      transplants with no induction. RESULTS: Patient and graft survival were similar,
      despite higher pretransplant acuity of illness and older age in the induction
      group. Acute rejection within the first 6 months occurred less commonly in the
      induction group (25.4% vs. 39.1%, P=0.01), despite significantly delayed
      initiation and lower doses of a calcineurin inhibitor. Mycophenolate mofetil was
      used more commonly in induction patients, but the efficacy of daclizumab in
      preventing rejection was independent of this. Patients with a pretransplant
      creatinine concentration 1.5 mg/dL or less had less rejection if they received
      induction. Renal function worsened in noninduction patients but showed sustained
      improvement throughout follow-up in induction patients with a pretransplant
      creatinine concentration greater than 1.5 mg/dL. Induction therapy provided
      better rejection prophylaxis among those requiring temporary calcineurin
      inhibitor cessation because of renal dysfunction. The incidences of histologic
      hepatitis C recurrence and cytomegalovirus infection were similar in each group.
      CONCLUSIONS: Liver recipients with and without pretransplant renal dysfunction
      have less acute rejection with daclizumab induction therapy. This is not
      associated with an increased risk of over-immunosuppression. Sustained renal
      improvement in recipients with pretransplant renal dysfunction is possible with
      daclizumab induction.

PMID- 15502723
TI  - TNP-470, an angiogenesis inhibitor, attenuates the development of allograft
      vasculopathy.
AB  - Fischer 344 rat recipients of Lewis allografts were treated with TNP-470, a
      synthetic fumagillin derivative and a well-established angiogenesis inhibitor.
      TNP-470 alone resulted in some prolongation of graft survival as compared with
      untreated recipients, but all grafts ultimately failed. In contrast, treatment
      with cyclosporine (CsA) from day 0 to 30 resulted in prolonged graft survival and
      marked cardiac allograft vasculopathy (CAV) by histology (mean score 2.28+/-0.2).
      There were many neovessels within the intima of CAV lesions. When TNP-470 was
      administered in combination with CsA from day 0 to 30, the degree of CAV was
      similar to that with CsA alone (mean score 2.22+/-0.26). However, when TNP-470
      was administered from day 30 to 120 after discontinuation of CsA, there was a
      marked reduction in the degree of CAV (mean score 1.08+/-0.11). Therefore, TNP
      470 interrupts the progression of CAV when given late but does not prevent its
      development when given immediately posttransplantation.

PMID- 15502724
TI  - Increased bronchoalveolar lavage human beta-defensin type 2 in bronchiolitis
      obliterans syndrome after lung transplantation.
AB  - Human beta-defensin-2 (HBD)2 is an antimicrobial peptide that participates in the
      innate host immune defense. HBD2 is present in bronchoalveolar lavage (BAL) fluid
      during conditions associated with airway inflammation but not in normal subjects.
      We measured HBD2 concentrations by semiquantitative Western analysis in BAL of
      prelung transplant patients (PRE) and postlung-transplant BAL associated with
      either "quiescent" histopathology (i.e., without acute cellular rejection or
      infection) (NORMAL POST) or with bronchiolitis obliterans syndrome (BOS). HBD2
      levels were not different for PRE (n=9) versus NORMAL POST-transplant BAL
      specimens (n=22) (204+/-180 vs. 82+/-60 pg/mL; P=NS). The BAL HBD2 concentrations
      were significantly elevated, however, with BOS (n=8) (1,270+/-430 pg/mL;
      P<0.001). HBD2 has been previously shown to elicit an adaptive immune response by
      means of recruitment of immature CD34 dendritic cells and memory (CD4/CD45RO) T
      lymphocytes through interactions with their chemokine receptor, CCR6.
      Furthermore, HBD2 with CD14 in human tracheobronchial epithelium can complex with
      "toll-like receptors" to activate the nuclear factor (NF)-kappaB pathway and
      therefore promote cytokine gene expression. We therefore speculate that complex
      interactions between adaptive and innate immunity may contribute to the
      propagation of airway inflammation in BOS.

PMID- 15502725
TI  - Antibody-mediated rejection after adult ABO-incompatible liver transplantation
      remedied by gamma-globulin bolus infusion combined with plasmapheresis.
AB  - Adult ABO-incompatible liver transplantation has been known to be associated with
      markedly desperate outcomes. Antibody-mediated rejection (AMR) has been
      recognized as one of the primary causes of these desperate outcomes, but its
      clinical features and significance have not been well understood. Recently, some
      clinicians have succeeded in improving the outcome of adult ABO-incompatible
      liver transplantation. However, in some transplant patients undergoing these
      treatments, AMR has still led to graft losses. We recently encountered two
      patients suffering from AMR after adult ABO-incompatible liver transplantation
      and remedied their conditions with various therapeutic modalities including
      direct hepatic infusion therapy and gamma-globulin bolus infusion therapy
      combined with plasmapheresis. In this article, we describe the clinical features
      of these patients and the therapeutic strategies we applied. Furthermore, we show
      the histologic course of the recovery from AMR in the second patient, from whom
      we were able to extract serial liver biopsies.

PMID- 15502726
TI  - Polyomavirus BK-specific immunity after kidney transplantation.
AB  - Failure to mount or maintain a protective immune response may influence the
      development of polyomavirus BK (BKV)-associated nephropathy (PVAN). However,
      limited data are so far available on BKV-specific immunity after kidney
      transplantation. BKV-specific cellular immune response was retrospectively
      analyzed in kidney recipients with or without BKV infection/reactivation by
      measuring the frequency of interferon (IFN)-gamma-secreting cells in peripheral
      blood. Patients with BKV-active infection and good renal function (n=6) had a
      mean BKV-specific lymphocyte frequency 2 log lower than healthy controls and in
      the same range as BKV-seropositive recipients without active infection (n=7).
      Patients with PVAN (n=5) revealed undetectable levels of BKV-specific cells.
      However, two patients from the latter cohort treated with immunosuppression
      reduction showed the emergence of specific immunity, with IFN-gamma production in
      the same range as healthy controls. Our preliminary data suggest that lack of
      protective immunity toward BKV may favor the occurrence of BKV active infection
      and influence the progression to PVAN.

PMID- 15502727
TI  - Calcium and calcitriol prophylaxis attenuates posttransplant bone loss.
AB  - We performed a prospective, randomized, double-blind study to determine whether
      calcium and calcitriol prevents posttransplant bone loss. Thirty-eight
      nondiabetic and 26 diabetic patients without prior steroid exposure undergoing
      their first kidney or kidney-pancreas transplant were randomized to calcium,
      calcium plus calcitriol, or placebo. Lumbar spine (LS), femoral neck (FN), and
      distal radius (DR) bone mineral density scans (BMDs) were obtained at baseline,
      6, and 12 months. At 1 year, patients treated with placebo experienced a 2%
      decline in BMD at the LS and DR and a 1.3% increase at the FN. In contrast,
      patients treated with calcium and vitamin D had a 0.1% decline at the LS and 2.9%
      and 4.8% increases at the DR and FN, respectively. Patients receiving
      cyclosporine had more bone loss than those receiving tacrolimus. Our results
      demonstrate a small therapeutic effect of calcium and calcitriol and suggest that
      tacrolimus is less osteotoxic than cyclosporine.

PMID- 15502728
TI  - End-stage heart failure with pulmonary hypertension: levosimendan to evaluate for
      heart transplantation alone versus combined heart-lung transplantation.

PMID- 15502729
TI  - Thrombophilia associated with anti-CD154 monoclonal antibody treatment and its
      prophylaxis in nonhuman primates.

PMID- 15502730
TI  - Iron therapy in renal transplant recipients.

PMID- 15502733
TI  - Reliability of hand-held dynamometry in assessment of knee extensor strength
      after hip fracture.
AB  - OBJECTIVES: To examine the reliability of hand-held dynamometry in assessing knee
      extensor strength in inpatients undergoing rehabilitation after hip fracture and
      to examine the discriminant validity of this measure. DESIGN: A total of 16
      subjects (14 women; mean +/- SD, 79 +/- 7 yrs) undergoing inpatient
      rehabilitation after hip fracture volunteered to participate. Isometric knee
      extensor strength of the fractured and unfractured sides was determined with a
      hand-held dynamometer. Subjects were retested 1-2 days after the initial testing
      session. RESULTS: Test-retest intraclass correlation coefficients were high for
      both the fractured (0.91) and unfractured legs (0.90). A low coefficient of
      variation was observed for both the fractured (15.3%) and unfractured (14.7%)
      sides. The maximal knee extensor strength was significantly different when
      comparing the fractured (7.9 +/- 3 kg) and unfractured (15.6 +/- 4 kg) legs. When
      comparing test 1 and test 2 mean values for the fractured leg, the scores
      significantly differed (t = 3.14, P < 0.01), with 13 of 16 subjects scoring
      higher on test 2. CONCLUSIONS: Hand-held dynamometry is a reliable and valid tool
      for assessment of knee extensor strength after hip fracture. Reduced knee
      extensor strength in the fractured leg may be an important component limiting
      rehabilitation progress in these patients.

PMID- 15502734
TI  - Grip strength in the frail elderly.
AB  - OBJECTIVE: To explore the relationship of impairment types to grip strength in
      the live-at-home frail elderly. DESIGN: All data in this cross-sectional study
      were collected in face-to-face interviews in subjects' homes by a nurse or
      occupational therapist. A total of 832 elders with activity limitations, as
      determined by the FIM instrument, participated in the study. Subjects were
      divided into three age groups (60-69, 70-79, and 80+ yrs) and four impairment
      groups: (1) minimally impaired, (2) visually impaired, (3) motor impaired, and
      (4) cognitively impaired. The outcome measures included the average (in
      kilograms) of three grip-strength trials per hand measured with the Jamar
      dynamometer at the second handle setting. RESULTS: There were significant
      differences in grip strength scores among all age groups, indicating that grip
      strength decreased with age. Among impairment groups, the minimally impaired and
      visually impaired groups had significantly greater grip strength scores than the
      motor-impaired and the cognitively impaired groups. There were no significant
      differences between the minimally impaired and visually impaired groups or
      between the motor-impaired and the cognitively impaired groups. CONCLUSIONS: Age
      and sex are not the only determining factors of grip strength in the frail
      elderly. The type of impairment affects grip strength as well. Thus, age-based
      norms may not be the only basis for interpreting evaluation data and establishing
      treatment goals with this population.

PMID- 15502735
TI  - Assessing persistent pain and its relation to affective distress, depressive
      symptoms, and pain catastrophizing in patients with chronic wounds: a pilot
      study.
AB  - OBJECTIVE: The purpose of this study was to examine pain experience among
      patients with chronic wounds, assess the utility of pain assessment scales for
      chronic wound-related pain, and determine the relation of wound-related pain to
      wound stage, affective distress, depressive symptoms, and pain catastrophizing.
      DESIGN: In this cross-sectional study of patients with a mix of chronic wounds (n
      = 69) recruited for a study evaluating a telemedicine system for assessing
      chronic wounds, 19 men (12 with spinal cord injury) with wound-related pain were
      identified. Questionnaires included the Numerical Pain Rating Scale, McGill Pain
      Questionnaire, Brief Symptom Inventory, Center for Epidemiologic Studies
      Depression Scale, and the catastrophizing scale of the Coping Strategies
      Questionnaire. RESULTS: The McGill Pain Questionnaire was more sensitive to pain
      experience than a single rating of pain intensity. Wound stage was positively
      related to severity of pain. Pain catastrophizing was positively related to pain
      intensity and higher levels of affective distress and depressive symptoms.
      CONCLUSIONS: Pain associated with chronic wounds is a significant clinical
      challenge for both patients and health practitioners.

PMID- 15502736
TI  - Increased bone resorption in the proximal femur in patients with hemiplegia.
AB  - OBJECTIVES: To investigate the relationship between the proximal femoral bone
      mineral density and bone resorption markers, determinants of calcium metabolism
      and vitamin D levels in elderly stroke patients. DESIGN: A total of 80 patients
      and 20 controls were enrolled in the study. Bone mineral density measurements
      were obtained at the proximal femur. In all subjects, 25-hydroxyvitamin D, 1,25
      dihydroxyvitamin D, intact parathyroid hormone, osteocalcin, deoxypyridinoline,
      and ionized calcium concentrations were measured. Barthel Index and Motricity
      Index Leg Score were recorded all patients. RESULTS: The serum concentrations of
      deoxypyridinoline, intact parathyroid hormone, and the mean serum ionized calcium
      levels were significantly higher in patients with stroke than that of the control
      subjects. The mean serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D
      concentrations in patients were significantly lower than those of the control
      group (P < 0.05). The bone mineral density of proximal femurs of paretic limbs
      was decreased significantly compared with those of the control group (P < 0.05).
      There were significant correlations between the Z score of the hemiplegic side
      and the patients' Barthel Index, Motricity Index Leg Score, 25-hydroxyvitamin D,
      1,25-dihydroxyvitamin D, calcium, and deoxypyridinoline. CONCLUSIONS: This study
      provides clear evidence that decreased mobility, vitamin D status, and bone
      turnover variables in patients after stroke are important factors in the greater
      bone loss in the paretic leg.

PMID- 15502737
TI  - Effect of increased sympathetic activity on electrical activity from myofascial
      painful areas.
AB  - OBJECTIVE: To investigate the effect of increased sympathetic outflow to muscle
      (by means of elevated intrathoracic pressure) on painful-area electrical
      activity. DESIGN: In six subjects with myofascial painful areas in trapezius
      muscles during normal respiration and during elevated intrathoracic pressure,
      electromyographic epochs were recorded from a monopolar needle electrode inserted
      over the painful area and advanced until action potentials were detected, a
      second needle electrode inserted to the same depth over a nontender control area,
      and surface electrodes placed nearby. RESULTS: The painful-area electromyographic
      activity increased (P < 0.05) from 49 +/- 53 microV during normal respiration to
      121 +/- 80 microV during elevated intrathoracic pressure. The control-area
      electromyographic activity and the surface-electrode electromyographic activity
      did not increase significantly. CONCLUSION: The significant electromyographic
      increase from painful areas and no significant increase from control channels are
      consistent with the view that sympathetic neural outflow increases painful-area
      electrical activity.

PMID- 15502738
TI  - Continuous muscle stretch prevents disuse muscle atrophy and deterioration of its
      oxidative capacity in rat tail-suspension models.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effect of continuous
      muscle stretch on disuse-atrophied muscles. DESIGN: Sprague-Dawley rats were used
      and divided into five groups: control group, hind limb suspended for 3 and 7
      days, and hind-limb suspension plus strenuous continuous muscle stretch for 3 and
      7 days. In the hind-limb suspension plus strenuous continuous muscle stretch
      groups, the gastrocnemius-plantaris-soleus muscles were stretched using a plastic
      plate that immobilized the ankle joint at the maximum dorsal flexed position
      during the hind-limb suspension period. The intracellular energy metabolism of
      the working muscle during electric stimulation was evaluated by phosphorus-31
      magnetic resonance spectroscopy in vivo. Changes in phosphocreatine, inorganic
      phosphate, and the intracellular pH were monitored to evaluate intramuscular
      oxidative capacity. Maximum tension and muscle wet mass were also measured.
      RESULTS: The oxidative capacity, muscle wet weight, and maximum tension decreased
      after hind-limb suspension. The muscle oxidative capacity at control levels was
      maintained during the first 3 days in muscles subjected to continuous strenuous
      stretch. It was also effective to prevent the decrease in muscle mass and maximum
      twitch tension during the initial 3 days. However, the effects did not persist.
      CONCLUSION: Continuous strenuous stretch was effective to prevent disuse muscle
      atrophy and its functional deterioration; however, its effects did not last long.

PMID- 15502739
TI  - Angioplasty and stenting of the intracerebral circulation.

PMID- 15502740
TI  - Research agenda for geriatric rehabilitation.
AB  - The Research Agenda Setting Process is a joint endeavor by the American
      Geriatrics Society and the Hartford Foundation to increase geriatric expertise in
      the surgical and related specialties. This article provides the results of the
      Research Agenda Setting Process project on research needs in geriatric
      rehabilitation, which included a systematic review of the literature and a group
      consensus process. Explicit research questions and methodologies were developed
      for three cross-cutting research needs in geriatric rehabilitation and for the
      rehabilitation of eight specific conditions affecting older individuals.

PMID- 15502741
TI  - Short-term effects of whole-body vibration on postural control in unilateral
      chronic stroke patients: preliminary evidence.
AB  - The short-term effects of whole-body vibration as a novel method of somatosensory
      stimulation on postural control were investigated in 23 chronic stroke patients.
      While standing on a commercial platform, patients received 30-Hz oscillations at
      3 mm of amplitude in the frontal plane. Balance was assessed four times at 45-min
      intervals with a dual-plate force platform, while quietly standing with the eyes
      opened and closed and while performing a voluntary weight-shifting task with
      visual feedback of center-of-pressure movements. Between the second and third
      assessments, four repetitions of 45-sec whole-body vibrations were given. The
      results indicated a stable baseline performance from the first to the second
      assessment for all tasks. After the whole-body vibration, the third assessment
      demonstrated a reduction in the root mean square (RMS) center-of-pressure
      velocity in the anteroposterior direction when standing with the eyes closed (P <
      0.01), which persisted during the fourth assessment. Furthermore, patients showed
      an increase in their weight-shifting speed at the third balance assessment (P <
      0.05) while their precision remained constant. No adverse effects of whole-body
      vibration were observed. It is concluded that whole-body vibration may be a
      promising candidate to improve proprioceptive control of posture in stroke
      patients.

PMID- 15502762
TI  - [Elastic stable intramedullary nailing in Ilizarov bone lengthening].
AB  - PURPOSE OF THE STUDY: Bone lengthening with the Ilizarov technique gives good
      results but certain disadvantages are common: possible axial deviation during
      lengthening, long time to bone union, risk of fracture after removal of the
      external fixator. Associating the Ilizarov technique with elastic stable
      intramedullary nailing (ESIN) commonly used in traumatology has to be evaluated.
      We conducted an experimental study and report results of the first clinical
      application. MATERIAL AND METHODS: Eleven lengthenings of the tibia were
      conducted in dogs aged 1 to 4 years using an Ilizarov external fixator associated
      with ESIN. Lengthening started on day 1 and continued for 28 days. X-rays were
      obtained every week during lengthening, then at 15 and 30 days during the
      fixation period and 30 days after removal of the fixator. In two cases,
      arteriography was performed. In a pilot clinical trial, fourteen patients (8
      males, 6 females) were treated with this method (1 humerus, 1 forearm, 7 femurs,
      5 tibias). Mean patient age was 14 years. RESULTS: In the experimental study, the
      x-rays showed rapid ossification of the regenerate which led to increased tibia
      length in 7 cases from 1.25 to 2 mm/day. Total bone union was observed in four
      dogs during the lengthening period. At day 15 of the fixation period, all tibia
      had fused with a good quality cortical bone and healing of the growth part of the
      regenerate. In three dogs, the external fixator was removed at day 15 of fixation
      and weight-bearing was total with the ESIN in place. No axial deviation and no
      skin problems were observed. The medullary artery was seen on the two
      arteriograms. In the clinical trial, bone union of the regenerate appeared
      earlier than in the Ilizarov series. The regenerate always displayed good density
      on the x-rays, proving intense bone activity. In three patients, the lengthening
      rate was increased to avoid premature bone fusion. The endosteal bone regenerate
      was obvious. Mean healing index was 18.6 days/cm (SD=6.2). Weight-bearing was
      allowed at six weeks. The desired correction was achieved in all patients and no
      complications were related to ESIN. DISCUSSION: Bone lengthening may be obtained
      with an intramedullary locking nail which avoids the use of an external fixator
      but also destroys the endomedullary circulation. Our experimental and clinical
      study shows that use of an ESIN does not inhibit the endosteal regenerate and
      seems to improve new bone formation. In many patients, the lengthening rate had
      to be increased to avoid premature bone fusion. When used in optimal conditions,
      ESIN can stimulate new endosteal and periosteal bone formation. In addition, ESIN
      increases shaft stability avoiding the risk of axial deviation. ESIN plays an
      additional role of stabilization after early removal of the external fixation.

PMID- 15502763
TI  - [Surgical treatment of posterior instability of the shoulder joint using an iliac
      bone block or an acromial pediculated bone block: outcome in eighteen patients].
AB  - PURPOSE OF THE STUDY: The posterior bone block procedure is a popular option for
      the treatment of involuntary posterior instability of the shoulder. The purpose
      of this study was to analyze the long-term results of this procedure using an
      iliac bone graft and to point out the advantages of Kouvalchouk technique using
      an acromial pediculated block. MATERIAL AND METHODS: Eighteen patients, ten men
      and eight women, mean age 27 years, were reviewed: thirteen were active in sports
      activities including four at the competition level. The duration of symptoms
      before surgery was four years on the average. One patient experienced recurrent
      dislocation, twelve suffered regular involuntary subluxation, and five had
      painful shoulders possibly related to posterior instability considering the
      arthroscopic findings. For nine patients (group 1), an iliac block was combined
      with the soft-tissue procedure. In nine others (group 2), the procedure described
      by Kouvalchouk was used to create a posterolateral acromial bone block with
      pediculated deltoid fibers. Functional outcome was assessed with the 100-point
      Duplay score. The position of the bone block and osteoarthritis were assessed on
      plain x-rays. RESULTS: Mean follow-up was 13.5 years in group 1 and 3.5 years in
      group 2. Four patients needed a revision procedure to remove a screw. At last
      follow-up, the average Duplay score was 78 points. Nine patients returned to
      their former sports activities. Seven patients were pain free and ten had
      moderate discomfort at effort. We did not observe any recurrent dislocation no
      subluxation but did have six patients who described apprehension. The mean Duplay
      score was 70 points in group 1 and 86 points in group 2. In two patients in group
      1, the x-rays showed signs of grade 3 or 4 osteoarthritis, which was related to
      an intra-articular screw in one; the other patient had had the same degenerative
      signs before surgery. Two patients developed grade 1 osteoarthritis. DISCUSSION
      AND CONCLUSION: The bone block procedure is effective for posterior instability
      of the shoulder. Occurrence of osteoarthritis, compared with the anterior bone
      block, is lower after long-term follow-up. The results of the Kouvalchouk
      procedure with an acromial pediculated bone block look promising. We recommend an
      additional capsuloplasty when inferior hyperlaxity is associated with posterior
      instability.

PMID- 15502764
TI  - [Surgical treatment for distal rupture of the biceps tendon].
AB  - PURPOSE OF THE STUDY: Avulsion of the distal biceps brachii tendon at the elbow
      is uncommon. We analyzed cases operated in our department in order to define
      etiological factors and surgical treatment outcome. MATERIAL AND METHODS: We
      reviewed retrospectively eleven patients, ten male patients, average age 43 years
      (range 37-59) with distal biceps tendon ruptures repaired anatomically with a
      double-incision technique and one other male patient whose tendon was attached to
      the brachialis anterior. Nine patients were seen for clinical assessment at least
      two years after operation. RESULTS: Average follow-up was 7 years (range 1-10).
      Patient satisfaction was good and all stated they would opt for surgical
      treatment again. The most common mechanism of injury was heavy weight lifting
      with the elbow at 90 degrees flexion or excentric loading on a flexed elbow. The
      dominant limb was injured in all patients. Eight patients had sustained injury
      during domestic activities and three during sports activities. Clinical diagnosis
      was the rule. MRI was useful in patients seen late after injury. We found nine
      cases of avulsion located at the bicipital tuberosity. All subjective results
      were good. Strength testing of the injured limbs revealed a loss of 30%
      supination strength and 40% supination endurance for the anatomic reinsertions.
      For the non-anatomic reinsertion, there was a 50% decrease in strength and 60%
      decrease in endurance. Clinical follow-up after seven years showed no nerve
      damage or heterotopic bone formation. DISCUSSION: Anatomic repair of distal
      biceps tendon rupture provides consistently good results. Attachment of the
      brachial tendon to the brachial anterior muscle cannot restore supination force.
      The two-incision technique with the extensor mass-splitting approach described by
      Boyd and Anderson lessens the risk of radial nerve plasty. CONCLUSION: Early
      anatomic reconstruction can restore more strength and endurance for supination.
      Attachment of the brachialis muscle must be considered in the event of late
      reconstruction. Subjective satisfaction with functional outcome has been
      excellent for all patients.

PMID- 15502765
TI  - [Radiocarpal dislocation: twelve cases and a review of the literature].
AB  - PURPOSE OF THE STUDY: Radiocarpal dislocation is an uncommon entity in
      traumatology. Proper management depends on the type of dislocation and the
      presence of concomitant injury. The purpose of this study was to detail the
      pathogenesis of radiocarpal dislocation and describe its complications and
      treatment. MATERIAL AND METHODS: Twelve radiocarpal dislocations were reviewed
      retrospectively. Nine were associated with multiple trauma. For this review,
      physical examination was performed to determine the functional status, presence
      of pain, joint motion, and grip force. The Green and O'Brien score as modified by
      Cooney was used to assess function. Grip force was measured with a Jamar
      dynamometer and weighted by the non-dominant/dominant ratio. Dumontier and Moneim
      classifications were used to define different types of radiocarpal dislocation.
      Radiological evaluation was based on anteroposterior (ulnar and radial
      inclination) and lateral views of the wrist. RESULTS: Dorsal displacement was
      observed for nine dislocations. All were associated with fractures (eleven
      fractures of the lateral cuneal process and eight fractures of the styloid
      process). Other associated injuries were distal radioulnar dislocation and
      intracarpal sprains (two scapholunate and two lunotriquetral). There were three
      median nerve compressions which all regressed without sequelae. Ten patients were
      treated by styloradial osteosynthesis alone and two patients by capsule-ligament
      suture via an anterior approach. Pinning was used to stabilize the two
      lunotriquetral injuries and the one neglected radioulnar dislocation. RESULTS: At
      last follow-up (mean 46.2 months), the overall functional outcome was
      satisfactory. The Green and O'Brien (modified by Cooney) score was excellent for
      one patient, fair for eight, and mediocre for three (75% satisfactory results).
      Distal radioulnar degeneration developed in the patient who had a neglected
      radioulnar dislocation. Three cases of radiocarpal degeneration were observed in
      patients with neglected scapholunate sprains whose wrist was symptomatic at last
      follow-up. DISCUSSION: Radiocarpal dislocation is associated with intracarpal
      fracture and/or injury. Intracarpal injury must be treated in order to limit the
      risk of future degeneration. Pure radiocarpal dislocation (or in association with
      a minimal fracture of the styloid) should be treated surgically, irrespective of
      the approach, in order to achieve capsule-ligament suture. Other radiocarpal
      dislocations can be simply reduced with osteosynthesis of associated fractures.
      Intracarpal and/or distal radioulnar lesions must be stabilized. Osteosynthesis
      or capsule-ligament suture must be achieved to obtain a satisfactory clinical
      result.

PMID- 15502766
TI  - [The cementless Duraloc acetabular component: 100 cases assessed after a minimum
      five year follow-up].
AB  - PURPOSE OF THE STUDY: The longevity of an acetabular implant depends in part on
      its resistance to mechanical stress. Long-term stability of an uncemented cup
      requires stable primary fixation. This can be achieved with press-fit components.
      MATERIAL AND METHODS: One hundred forty-nine Duroloc press-fit acetabular
      implants were studied after a minimum follow-up of 60 months. Among these 149
      cups, 100 were analyzed with a mean follow-up of 60 months. Twenty-two patients
      were lost to follow-up, 19 were contacted by telephone, and eight had died.
      Clinical and radiological criteria were used to assess outcome. Digitalized x
      rays were processed with Imagika (View Tec, Saint-Maurice, France) to determine
      the position of the implant in two-dimensional space, inclinaison, anteversion,
      polyethylene wear, bone-implant contact, and presence of ossifications. Seventy
      percent of the patients underwent arthroplasty for degenerative hip disease.
      RESULTS: The cohort included 40 women and 60 men. Mean age at surgery was 59.4
      years, range 30-80 years. The Postel-Merle-d'Aubigne score improved from 10 to
      16. Mean polyethylene wear was 0.5 mm with an annual rate of 0.087 mm/yr. Among
      the 57 cup-bone spaces present postoperatively, 41 had filled at last follow-up
      (78%). There were no cases of osteolysis. Peri-prosthetic ossifications were
      observed in 50 patients (16 stage I, 12 stage II, 19 stage II, and 3 stage IV).
      Medial displacement of the cup > 4 mm was observed in one patient and ascension >
      4 mm in four patients who had no other sign of loosening. Complications were:
      dislocation (n=15), phlebitis (n=2), sciatalgia (n=1) and infection (n=1).
      DISCUSSION: This retrospective series revealed an unacceptable dislocation rate
      with no correlation with implant positioning error in comparison with the
      biomechanical position of the healthy hip. The non-hemispheric shape of the
      implant and the beveled edge of the polyethylene insert could be implicated,
      particularly since none of the implants had a polyethylene overhang. The mean
      annual wear (0.087 mm) was relatively high compared with cemented cups. Age was
      the only factor correlated with wear. Migrations were difficult to interpret.
      Medialization or ascension of the implant was not associated with any clinical
      sign suggestive of loosening. The poor reproducibility of the x-rays cannot
      explain these findings. Secondary repositioning of the implant might be involved.
      CONCLUSION: The high rate of dislocation and the frequency of excessive wear have
      led us to abandon this implant for more hemispheric cups.

PMID- 15502767
TI  - [Mechanical properties of human femoral head allografts after physico-chemical
      treatment (Osteopure)].
AB  - PURPOSE OF THE STUDY: Bone grafts and bone substitutes must be biocompatible
      osteoconductors with satisfactory mechanical properties similar to native bone.
      When the bone treatment is conducted under specific conditions, the elasticity
      module under infra-maximal loading can be optimized to achieve reproducible
      values. The purpose of this work was to determine the effect of the cleaning and
      sterilization process using Osteopure on the biomechanical properties of
      trabecular bone harvested from human femoral heads. MATERIAL AND METHOD: Seventy
      trabecular bone samples were tested: group 1F (fresh samples); group 1N (after
      application of Osteopure cleaning); group 1S (after Osteopure cleaning and
      sterilization). Non-destructive and destructive tests (group 1D) were performed.
      Two fresh femoral heads were used as controls for the destructive test (group 2).
      The first non-destructive test was applied directly after section (group 1F).
      Other samples were then purified with Osteopure treatment and a second non
      destructive test was conducted (group 1N). A third non-destructive test was
      conducted after sterilization with 25 kgray radiation (group 1S). Treatments 1
      and 2 were performed by OST Developpement SA (Clermont-Ferrand). Finally a
      destruction test was applied along the directional axis (group 1D). For the 31
      samples in group 2 (control) the destructive test was applied along the
      directional axis immediately after section. Compression tests were performed at a
      deformation speed of 3 mm/min for 0.3% deformation. RESULTS: The Young module did
      not exhibit any significant difference between the three steps of the testing in
      the three orthogonal directions. The Young module was not significantly different
      between group 1F and group 2 (controls). Maximal force of compression was
      significantly different (P<0.01). There was a linear relationship between maximal
      force at rupture and the Young module obtained during destructive tests, for
      groups 1D and 2 respectively. The compression curves obtained from sterilized
      samples (group 1D) were not significantly different from those observed for fresh
      trabecular bone in group 2 (controls). DISCUSSION: The Young module values
      measured from 70-673 MPa. For non-destructive tests, the module values were to
      the order of 64% of those obtained for destructive tests. Decreased maximal force
      of rupture observed for treated samples in comparison with fresh samples can be
      explained by the extraction of most of the lipids. CONCLUSION: The Osteopure
      method does not alter stiffness of bone allografts. The elasticity module
      observed in treated bones is close to that observed in fresh bones. Mechanical
      resistance to compression is however only half the force of compression observed
      in the hip joint for daily activities. The linear relationship between the
      elasticity mode and loading required for rupture is not affected by treatment
      with Osteopure. The advantages related to elimination of prions or viral
      contamination appear by far to be more important than the minor changes observed
      in the mechanical characteristics of allografts.

PMID- 15502768
TI  - [Irreducible knee dislocation by medial capsulo-ligament incarceration].
AB  - PURPOSE OF THE STUDY: Irreducible dislocation of the knee is exceptional.
      Incarceration of the capsulo-ligamentary elements in the inter-condylar notch is
      a particular causal mechanism. We report four new cases and review the literature
      to describe the diagnostic and therapeutic approach. MATERIAL AND METHODS:
      Between January 2001 and January 2002, four patients underwent surgery after
      trauma (wind surf, ski accidents) producing an irreducible knee dislocation. Mean
      patient age was 53 years and mean follow-up was 16 months. The IKDC
      classification was used to assess outcome. RESULTS: Physical examination revealed
      characteristic signs: a groove facing the medial joint line with signs of
      cutaneous suffering just above and a fold line behind the medial condyle.
      Orthopedic reduction failed. Surgery was performed in all cases and revealed
      incarceration of the entire capsulo-ligamentary structure in the intercondylar
      notch with the medial condyle in an extra-articular position. After surgical
      reduction, healing was achieved in all cases without cutaneous necrosis. The mean
      subjective IKDC score was 53.9. DISCUSSION: Orthopedic reduction is impossible in
      about 4% of all cases of knee dislocation. Clinical signs are characteristic when
      the medial capsulo-ligamentary structures are incarcerated in the intercondylar
      notch; the anatomic injury is almost always the same. Vasculonervous
      complications are exceptional but an emergency arteriography should be obtained
      to rule out an infra-clinical intimal lesion. Cutaneous necrosis is a specific
      complication of irreducible dislocation. Early and complete reduction is required
      to prevent necrosis. Arthroscopic management raises the risk of compartment
      syndrome since peripheral lesions are not healed. Satisfactory functional
      recovery requires associated repair of the cruciate ligaments. CONCLUSION: This
      type of irreducible dislocation of the knee is a specific clinical entity. It
      usually results from postero-lateral rotation but may exceptionally occur after
      lateral dislocation. A groove associated with a fold line indicates the need for
      rapid surgical reduction to avoid the risk of cutaneous necrosis.

PMID- 15502769
TI  - [Ankylosed spine fractures with spondylitis or diffuse idiopathic skeletal
      hyperostosis: diagnosis and complications].
AB  - PURPOSE OF THE STUDY: Spinal fractures in patients with ankylosing spondylitis or
      idiopathic skeletal hyperostosis can raise difficult diagnostic and therapeutic
      problems. Spinal fracture is well known in ankylosing spondylitis but exceptional
      in diffuse idiopathic skeletal hyperostosis. The purpose of the present work was
      to identify clinical and radiological features in patients with ankylosing
      spondylitis, to determine whether similar risks and clinical expression are
      observed in patients with diffuse idiopathic skeletal hyperostosis, and to
      present a radiological classification of these fractures. We did not assess
      therapeutic methods in the present study. MATERIAL AND METHODS: Forty-eight
      fractures in 48 patients were observed over a period of 17 years. Twenty patients
      (mean age 62 years) had ankylosing spondylitis and 28 patients (mean age 81
      years) had diffuse idiopathic skeletal hyperostosis. A fall was the immediate
      cause of the fracture in more than half of the patients. No notion of trauma
      could be identified in six patients. The radiological classification was
      established as follows; type I open-wedge anterior fracture, type II "sawtooth"
      fracture, type III occult or radiologically invisible fracture, type IV non
      specific fractures comparable to other spinal fractures. A computed tomography
      was obtained in all patients seen after 1992 and magnetic resonance imaging was
      performed in case of suspected extradural hematoma. The ASIA classification (as
      modified by Frankel) was used for cord injuries. Clinical course and
      complications were noted. RESULTS: Diagnosis was established the day of fracture
      in 32 patients (12 spondylitis and 20 hyperostosis) and between day 2 and 30 for
      16 (8 spondylitis and 8 diffuse idiopathic skeletal hyperostosis). The
      radiological classification was: type I n=30, type II n=4, type III n=8, type IV
      n=6 (one odontoid fracture, five compression fractures). Three patients had
      extradural hematomas (2 spondylitis and 1 hyperostosis). Thirty-four patients (11
      spondylitis and 23 hyperostosis) had cord injuries, including 16 with a symptom
      free interval. The ASIA classification was: type A n=4, type B n=6, type C n=20,
      type D n=4. Thirty-two patients died within the first three months after spinal
      fracture (10 spondylitis and 22 hyperostosis), due to bed rest related
      complications in 30. One patient died after rupture of an aortic aneurysm.
      DISCUSSION: Spinal fractures in patients with ankylosing spondylitis or diffuse
      idiopathic skeletal hyperostosis generally occur spontaneously or after low
      energy trauma. Subsequent complications have serious consequences. Late diagnosis
      either results from missing a radiologically visible fracture or from the
      presence of an occult "paper thin" fracture. We do not have experience with
      diagnostic scintigraphy or magnetic resonance imaging. In our opinion, repeating
      standard x-rays the second and third weeks and use of a spiral scan or multiple
      spiral scan could provide early diagnosis. CONCLUSION: The possible diagnosis of
      spinal fracture should be explored very extensively in patients with a
      symptomatic ankylosed spine who present symptoms compatible with spinal fracture,
      with or without trauma.

PMID- 15502770
TI  - [Extraskeletal osteosarcoma of the forearm: a case report].
AB  - Extraskeletal osteosarcoma is a rare soft tissue tumor. We report an exceptional
      case located in the forearm. A 62-year-old woman consulted for a tumor of the
      right forearm which she had noticed for six months. Physical examination revealed
      a 10 x 12 cm tumor with an ulcerated center. MRI demonstrated a heterogeneous
      mass exhibiting no connection with the bone or subjacent periosteum. Wide
      surgical resection was performed. The pathology study of the operative specimen
      confirmed the diagnosis of soft tissue osteosarcoma. The patient was given
      postoperative chemotherapy and was free of local recurrence or metastasis
      eighteen months after surgery. We discuss the present case and review data
      reported in the literature.

PMID- 15502771
TI  - [Tumoral calcinosis of the plantar forefoot: a case report and review of the
      literature].
AB  - Tumoral calcinosis of the plantar forefoot is an uncommon benign condition
      resulting from deposits of hydroxyapatite crystals in periarticular soft tissue.
      The pathogenic mechanism remains to be clarified. This condition is generally
      observed in young subjects and a hereditary pattern is often discovered. We
      report the clinical, radiological, and biological findings in a case of right
      forefoot tumoral calcinosis observed in a sixteen-year-old girl and describe the
      surgical treatment and pathology results. Based on this case and a review of the
      literature, we discuss the different pathogenic hypotheses as well as the
      appropriate diagnostic and therapeutic approach.

PMID- 15502772
TI  - [Arthrosynovial cyst of the hip after total hip arthroplasty with a ceramic-on
      ceramic interface].
AB  - An inguinal arthrosynovial cyst of the hip joint developed after total hip
      arthroplasty leading to compression of the femoral vein. This complication
      occurred after implantation of a non-cemented prosthesis with a ceramic-on
      ceramic interface inserted in a polyethylene sandwich. Multiple foreign bodies
      composed of both ceramic and polyethylene particles were visualized
      microscopically. Later, rupture of the joint interface required implant
      replacement. This cyst was a precursor sign of a deteriorating prosthesis
      surface.

PMID- 15502785
TI  - Quantitative assessment of aortic sclerosis using ultrasonic backscatter.
AB  - BACKGROUND: The development of therapeutic interventions to prevent progressive
      valve damage is more likely to limit the progression of structural damage to the
      aortic valve with normal function (aortic sclerosis [ASC]) than clinically
      apparent aortic stenosis. Currently, the ability to appreciate the progression of
      ASC is compromised by the subjective and qualitative evaluation of sclerosis
      severity. METHODS: We sought to reveal whether the intensity of ultrasonic
      backscatter could be used to quantify sclerosis severity in 26 patients with ASC
      and 23 healthy young adults. Images of the aortic valve were obtained in the
      parasternal long-axis view and saved in raw data format. Six square-shaped 11 x
      11 pixel regions of interest were placed on the anterior and posterior leaflets,
      and calibrated backscatter values were obtained by subtracting the regions of
      interest in the blood pool from the averaged backscatter values obtained from the
      leaflets. RESULTS: Mean ultrasonic backscatter values for sclerotic valves
      exceeded the results in normal valve tissue (16.3 +/- 4.4 dB vs 9.8 +/- 3.3 dB, P
      < .0001). Backscatter values were greater (22.0 +/- 3.5 dB) in a group of 6
      patients with aortic stenosis. Within the sclerosis group, the magnitude of
      backscatter was directly correlated (P < .05) with a subjective sclerosis score,
      and with transvalvular pressure gradient. Mean reproducibility was 2.4 +/- 1.8 dB
      (SD) between observers, and 2.3 +/- 1.7 dB (SD) between examinations. CONCLUSION:
      Measurement of backscatter from the valve leaflets of patients with ASC may be a
      feasible means of following the progression and treatment response of aortic
      sclerosis.

PMID- 15502786
TI  - Potential relationships among myocardial stiffness, the measured level of
      myocardial backscatter ("image brightness"), and the magnitude of the systematic
      variation of backscatter (cyclic variation) over the heart cycle.
AB  - BACKGROUND: In a number of recently published studies comparing measurements from
      patients with those from control subjects, a decreased magnitude of the
      systematic variation of backscattered energy over the heart cycle (cyclic
      variation) is accompanied by an increased level of overall myocardial backscatter
      (calibrated myocardial image brightness) when measured at a specific phase of the
      heart cycle (eg, end systole or end diastole). The goal of this study was to
      investigate whether this observation is consistent with predictions based on a
      model of the mechanisms of cyclic variation incorporating changes in relative
      intracellular and extracellular acoustic impedance over the heart cycle. METHODS:
      A previously described 3-component Maxwell-type model of muscle mechanics
      representing cardiac cell mechanical behavior was utilized to predict the
      systematic variation in the relative acoustic impedance differences between
      intracellular and extracellular elastic properties over the heart cycle and hence
      the observed magnitude of cyclic variation and overall myocardial scattering
      level. Predictions were obtained for a series of specific values of relative
      intracellular and extracellular acoustic impedance. RESULTS: Results indicate
      that the predicted magnitude of cyclic variation can be directly related to the
      overall myocardial backscatter level. For example, specific changes in the
      acoustic impedance (stiffness properties) of the extracellular matrix without any
      change in the intracellular acoustic impedance result in predicted values of 
      43.5 dB, -38.5 dB, and -33.5 dB for end-diastolic myocardial backscatter levels
      with corresponding values of 5.0 dB, 2.5 dB, and 1.3 dB for the predicted
      magnitude of cyclic variation, respectively. CONCLUSION: This study suggests that
      observed decreases in the magnitude of cyclic variation with concomitant
      increases in the measured overall myocardial backscatter level are consistent
      with predictions from a model based on the relative acoustic impedance
      differences between intracellular and extracellular elastic properties over the
      heart cycle. These results suggest that ultrasonic backscatter measurements may
      provide a noninvasive approach for assessing some relationships among myocardial
      stiffness, degree of fibrosis, and contractile performance.

PMID- 15502787
TI  - Analysis of the effect of temporal filtering in myocardial tissue velocity
      imaging.
AB  - Signal filtering to reduce random noise may compromise the reliability of tissue
      velocity measurements. This study evaluates the influence of temporal filters on
      time and velocity variables derived from myocardial tissue velocity images
      acquired in 15 healthy individuals at a high frame rate (142-184 Hz). Different
      time and velocity variables from the basal septum were analyzed offline before
      and after temporal filtering from 20 to 60 milliseconds in 10-millisecond steps
      using software enabling retrieval of myocardial Doppler velocity and 2
      dimensional information from different cardiac locations during the same cardiac
      cycle. Filtering affected the results by increasing variability of time and by
      underestimation of velocity variables, the rapid isovolumic events being
      particularly filter sensitive. In addition, at a certain range of sampling rate,
      ambiguity of filtering effect was observed. This ought to be considered if an
      optimal, high-fidelity tissue Doppler velocity signal is to be obtained.

PMID- 15502788
TI  - Factors associated with mitral annular systolic and diastolic velocities in
      healthy adults.
AB  - BACKGROUND: Measurements of systolic mitral annular velocity (S'), early
      diastolic mitral annular velocity (E'), and late diastolic mitral annular
      velocity (A') are used to assess left ventricular (LV) function. OBJECTIVE: We
      sought to investigate the relationship between septal and lateral annular
      velocities and determine whether these velocities are related to body size
      (including body mass index [BMI]), heart rate (HR), blood pressure, or LV mass.
      METHODS: A total of 60 healthy participants who were normotensive, between age 20
      and 52 years, underwent standard echocardiography and measurement of septal and
      lateral S', E', and A'. RESULTS: The lateral velocity exceeded the septal
      velocity for S', E', and A'. There was only weak to moderate correlation between
      the velocities at the two sites (r = 0.43-0.60). Septal S' was positively
      correlated with height and HR, and lateral S' was correlated with HR. Septal E'
      was negatively correlated with age, BMI, LV mass, and diastolic blood pressure,
      but lateral E' was only negatively correlated with age and BMI. Septal A' was
      positively correlated with age, HR, and BMI, whereas lateral A' was only
      positively associated with age. CONCLUSIONS: S', E', and A' are not only of
      different magnitudes at the septal and lateral sites, but are not closely
      correlated. There are relationships between annular velocities and body size, HR,
      blood pressure, and LV mass that differ between the septal and lateral annulus,
      providing a possible explanation for the lack of close correlation in these
      velocities and suggesting that these variables may need to be considered when
      interpreting annular velocities.

PMID- 15502789
TI  - Noninvasive assessment of right atrial pressure using Doppler tissue imaging.
AB  - Right atrial pressure (RAP) reflects volume and pressure hemodynamics of right
      cardiac chambers. Previous attempts for noninvasive assessment of RAP include 2
      dimensional and Doppler correlates of RAP, which require the presence of optimal
      subcostal views that may not be always feasible. In this study we utilized
      Doppler tissue imaging of the tricuspid annulus in the apical 4-chamber view, for
      noninvasive assessment of RAP. An inverse relationship was demonstrated between
      mean RAP and the interval between the end of the systolic annular motion to the
      onset of the early diastolic filling wave (right ventricular regional isovolumic
      relaxation time).

PMID- 15502790
TI  - Analysis of fossa ovalis membrane velocities by transesophageal Doppler tissue
      echocardiography: a novel approach to functional assessment of patent foramen
      ovale.
AB  - BACKGROUND: Recent studies have suggested that a higher mobility of the fossa
      ovalis membrane (FOM) may be associated with an increased risk for stroke in
      patients with patent foramen ovale (PFO). The current study analyzed whether
      Doppler tissue echocardiography is useful for quantitation of FOM motion
      velocities. METHODS: FOM dynamics were prospectively studied in 107 consecutive
      patients (average age 50.7 +/- 15.3 years, 48 men) with in sinus rhythm who
      underwent transesophageal echocardiography for various indications. With pulsed
      wave Doppler tissue echocardiography interrogation, a characteristic quadrophasic
      signal was recorded in all patients, consisting of a positive wave toward the
      left atrium (A-wave) at late diastole, followed by a negative wave (B-wave)
      toward the right atrium, a pronounced, again positive wave during midsystole (C
      wave), and a final negative wave (D-wave). RESULTS: Peak velocities of A-wave, B
      wave, C-wave, and D-wave were 0.08 +/- 0.02 m/s, 0.11 +/- 0.05 m/s, 0.17 +/- 0.07
      m/s, and 0.14 +/- 0.06 m/s, respectively. In 21 of 107 (19.6%) patients, PFO was
      detected. Patients with PFO had significantly higher C-wave and D-wave peak
      velocities compared with the 86 patients without PFO (0.23 +/- 0.10 m/s vs 0.15
      +/- 0.05 m/s, P < .001 and 0.16 +/- 0.07 m/s vs 0.12 +/- 0.06 m/s, P = .04,
      respectively). CONCLUSIONS: Assessment of FOM dynamics using Doppler tissue
      echocardiography is feasible. It allows definition of a characteristic
      quadrophasic FOM motion pattern, thereby providing new insights into the
      physiology of FOM mobility. Patients with PFO were found to have increased FOM
      mobility compared with patients without PFO.

PMID- 15502791
TI  - Echocardiographic characteristics of secundum-type atrial septal defects in adult
      patients: implications for percutaneous closure using Amplatzer septal occluders.
AB  - The aim of the study was to analyze echocardiographic characteristics of isolated
      secundum-type atrial septal defects (ASD II) in adult patients and their
      implications for percutanous closure using Amplatzer septal occluders. The study
      population consisted of 64 consecutive adult patients with isolated ASD II (mean
      age 43.6 +/- 15.9 years). Patients were evaluated using both transthoracic and
      transesophageal echocardiography. Defects in 29 of 64 patients (45.3%) fulfilled
      the echocardiographic criteria for percutaneous closure. The mean defect diameter
      in the study was 22.2 +/- 9.5 mm. In all, 13 morphologic variations of ASD II
      were detected. A statistically significant correlation between defect size and
      the number of deficient defect rims was found. Less than 50% of ASD II in adult
      patients fulfilled the echocardiographic criteria for percutaneous closure using
      Amplatzer septal occluders. Because others have demonstrated growth of ASD II
      over time, we presume that in some patients, defect growth is associated with
      attenuation or even disappearance of defect rims causing changing defect
      morphology with increasing defect size.

PMID- 15502792
TI  - Three-dimensional color Doppler echocardiography for assessing shunt volume in
      atrial septal defects.
AB  - Background Three-dimensional color Doppler echocardiography has been used to
      assess cardiac blood flow in experimental settings. We tested whether this
      technique can be applied to assess transatrial shunt flow in patients with atrial
      septal defect in a clinical setting. Methods In 46 consecutive patients with
      atrial septal defects, shunt flow was assessed during cardiac catheterization
      using the Fick method and by conventional 2-D quantitative transesophageal
      Doppler echocardiography. The averaged values for shunt flow obtained by both
      methods were used as a reference. Transesophageal 3-D color Doppler
      echocardiography was performed for analysis of the 3-D flow velocity field of
      transatrial shunt flow. Shunt volume was calculated by application of the Gauss
      theorem. Results We found a close correlation between shunt volume (L/min)
      obtained by either 3-D color Doppler echocardiography or the reference methods (
      r = 0.981, P < .001). Using 3-D color Doppler data to predict the reference
      values, 95% confidence limits were -11.5 to +11.6%. Conclusions Shunt flow in
      patients with atrial septal defects can be assessed in a clinical setting by
      transesophageal 3-D color Doppler echocardiography.

PMID- 15502793
TI  - Geometric changes of mitral annulus assessed by real-time 3-dimensional
      echocardiography: becoming enlarged and less nonplanar in the anteroposterior
      direction during systole in proportion to global left ventricular systolic
      function.
AB  - OBJECTIVE: We sought to investigate the geometric changes of the mitral annulus
      during systole in relation to global left ventricular (LV) systolic function
      using real-time 3-dimensional (3D) echocardiography. METHODS: Real-time 3D
      echocardiography was performed in 23 patients with global LV systolic dysfunction
      with ejection fraction of 37 +/- 19% and 9 control subjects with ejection
      fraction of 62 +/- 4%. Volumetric data were divided into 9 rotational apical
      planes (angle increment = 20 degrees) using 3D software. Nine rotational annular
      dimensions (ADs) were measured in all planes in early and late systole. Nonplanar
      angle (NPA) of the annulus between two vectors from two hinge points of the
      annulus in the anteroposterior plane to the center between two commissures in the
      commissure-commissure plane was measured during early and late systole.
      Fractional changes of NPA and AD were defined as changes in percentage during
      systole. RESULTS: NPA significantly increased during systole (early, 145 +/- 12
      degrees; late, 160 +/- 9 degrees; P < .01). Among 9 ADs, 3 anteroposteriorly
      directed ADs showed the most prominent fractional increases during systole in all
      patients. Both fractional changes of NPA ( R 2 = 0.87, P < .01) and the
      anteroposterior dimension, AD 1 ( R 2 = 0.85, P < .01) showed significant
      positive correlation with global LV systolic function. CONCLUSIONS: Real-time 3D
      echocardiography demonstrated that saddle shape of the mitral annulus was getting
      enlarged and less nonplanar mainly in the anteroposterior direction during
      systole. These geometric changes were proportional to the global LV systolic
      function.

PMID- 15502795
TI  - Association of Doppler-derived myocardial performance index with albuminuria in
      patients with diabetes.
AB  - Albuminuria is a predictor of cardiovascular morbidity and mortality in patients
      with diabetes. In this study, the relationship of albuminuria with left
      ventricular function by using myocardial performance (Tei) index together with
      conventional function parameters was aimed to be examined. We studied 123
      patients with diabetes but without obvious coronary artery disease and heart
      failure. The patients were divided into 3 groups: 50 with no albuminuria; 49 with
      microalbuminuria; and 24 with macroalbuminuria. The Tei index in the patients
      with diabetes was increased (0.59 +/- 0.12). A significant stepwise increase in
      the Tei index was seen from no albuminuria to macroalbuminuria (0.51 +/- 0.1,
      0.61 +/- 0.1, and 0.7 +/- 0.08, respectively). Tei index was positively
      correlated with isovolumic relaxation time, isovolumic contraction time, the
      duration of diabetes, left ventricular mass index, the levels of fibrinogen,
      creatinine, total cholesterol, and low-density lipoprotein cholesterol. The
      association of amount of secreted albumin into urine with echocardiographic
      parameters (Tei index, ejection fraction, peak early and late transmitral filling
      velocity ratio, peak early transmitral filling velocity decelaration time,
      isovolumic relaxation time, left ventricle mass index) was evaluated by using
      regression analysis. It was observed that amount of albumin was significantly
      associated with only Tei index ( P = .001, B = 0.3). It was found that there was
      a strong relation between Tei index and albuminuria and also its degree.
      Therefore, it was concluded that Tei index may be a sensitive marker for
      diagnosis of ventricular dysfunction in patients with diabetes and prognosis of
      diabetes.

PMID- 15502796
TI  - Paradoxical changes in brain natriuretic peptide levels and loading conditions
      after intravenous conscious sedation.
AB  - BACKGROUND: Elevated filling pressure and wall stress have been proposed as
      stimuli for elevated brain natriuretic peptide (BNP) levels. Narcotic and
      benzodiazepine sedation, such as is used for transesophageal echocardiography
      (TEE), is known to decrease filling pressures. We hypothesized that lower filling
      pressure and wall stress associated with intravenous conscious sedation (IVCS)
      would lead to lower BNP levels. METHODS: We studied BNP levels, blood pressure,
      and echocardiographic indices of filling pressure and wall stress before and
      after IVCS and TEE. RESULTS: When data before and after IVCS and TEE were
      compared, mean blood pressure decreased (149 +/- 24/83 +/- 14 mm Hg vs 126 +/-
      29/69 +/- 14; P < .01), as did mitral Doppler E wave velocity (82 +/- 23 cm/s vs
      76 +/- 22; P < .05), right ventricular/atrial gradient (31 +/- 10 mm Hg vs 29 +/-
      13; P < .05), and wall stress. However, BNP levels increased (195 +/- 407 pg/mL
      vs 238 +/- 458; P < .01). CONCLUSIONS: In a series of patients undergoing
      clinically indicated TEE, BNP levels increase above baseline after IVCS. The
      increase in BNP occurs despite lower blood pressure, lower mitral Doppler E
      velocity, lower right ventricular/atrial gradient, and lower wall stress compared
      with baseline. The mechanism of the paradoxical increase in BNP is not entirely
      clear, but it may conceivably be a result of counterregulatory hormone release
      caused by acute decrease in blood pressure.

PMID- 15502797
TI  - Forward and store telemedicine using Motion Pictures Expert Group: a novel
      approach to pediatric tele-echocardiography.
AB  - BACKGROUND: Live transmission of echocardiograms over integrated services digital
      network lines is accurate and has led to improvements in the delivery of
      pediatric cardiology care. Permanent archiving of the live studies has not
      previously been reported. Specific obstacles to permanent storage of telemedicine
      files have included the ability to produce accurate images without a significant
      increase in storage requirements. OBJECTIVE: We evaluated the accuracy of Motion
      Pictures Expert Group (MPEG) digitization of incoming video streams and assessed
      the storage requirements of these files for infants in a real-time pediatric tele
      echocardiography program. RESULTS: All major cardiac diagnoses were correctly
      diagnosed by review of MPEG images. MPEG file size ranged from 11.1 to 182 MB
      (56.5 +/- 29.9 MB). CONCLUSIONS: MPEG digitization during live neonatal
      telemedicine is accurate and provides an efficient method for storage. This
      modality has acceptable storage requirements; file sizes are comparable to other
      digital modalities.

PMID- 15502798
TI  - Left atrial hematoma complicating inferior myocardial infarction.
AB  - Intramyocardial dissecting hematoma after myocardial infarction is a rare
      condition. Previous reports have documented that these hematomas form almost
      exclusively in the myocardium adjacent to the culprit coronary lesion. We report
      a case of coexistent intramyocardial dissecting hematoma and ventricular rupture
      that arose as a consequence of a distal right coronary artery occlusion.
      Unusually, there was a very long dissection plane, which crossed the
      atrioventricular groove, with the hematoma manifesting on the opposite side of
      the heart (left atrium) to the infarcted myocardium (inferior wall).

PMID- 15502799
TI  - Subacute effusive-constrictive pericarditis: diagnosis by serial
      echocardiography.
AB  - We report the case of a 30-year-old man with acute pericarditis in whom effusive
      constrictive physiology developed rapidly in less than 2 weeks. Serial
      echocardiography demonstrated a dramatic change in the appearance of the
      pericardial effusion and the pericardial space. The patient underwent
      pericardiectomy with symptom relief. The findings at operation included a
      markedly thickened and inflamed pericardium. The case highlights the role of
      echocardiography in the evaluation of patients with pericardial disease and the
      echocardiographic features that prompted early surgical intervention.

PMID- 15502800
TI  - Use of peak Doppler gradient across ventricular septal defect leads to
      underestimation of right-sided pressures in a patient with M-shaped Doppler
      signal: a case report.

PMID- 15502801
TI  - Right ventricular strain in pulmonary embolism by Doppler tissue
      echocardiography.
AB  - For patients with submassive pulmonary embolism, failure of the right ventricle
      can often be visualized by 2-dimensional echocardiography. We used strain
      analysis to demonstrate changes in the regional right ventricular free wall
      performance during the acute and recovery stages of pulmonary embolism.

PMID- 15502802
TI  - A severe case of Austrian syndrome.

PMID- 15502803
TI  - The transition from an analog to a digital echocardiography laboratory: the Mayo
      experience.
AB  - Our echocardiography laboratory has completed the transition from an analog to a
      digital imaging laboratory. The process involved a thorough analysis of the
      practice and design of a complete digital solution. After an effective
      implementation of a robust reporting solution, the transition to digital imaging
      ensued. The implementation plan for digital imaging enabled the transition to be
      made without adversely affecting the practice, which has an average daily
      examination load of more than 200 patients. Full-load testing simulations were
      required on high-end image processing review workstations, high-speed local area
      network connections to each imaging suite, and new clustered imaging servers. We
      had to test the ability of approximately 100 ultrasound machines with 3
      idiosyncratic ultrasound platforms to allow digital image transfer to the new
      imaging servers over the local area network. Our sonographer, allied health, and
      physician staff of more than 250 persons had to be trained to adapt to important
      changes that the digital echocardiographic image acquisition and review platform
      would have on their specific roles in the laboratory. The efficiency of the
      implementation, reporting, and imaging resulted in improved staff resource
      allocation. The lessons learned may benefit laboratories with a similar interest
      in making the transition to a digital imaging laboratory with minimal effect on
      patient scheduling and staff satisfaction. The effect of the transition to a
      completely digital laboratory on operating expenses, imaging, and reviewing
      systems and the impact on the clinical practice of echocardiography at our
      institution are presented, with emphasis on the particular aspects of
      transitioning to digital imaging.

PMID- 15502804
TI  - Overexpression and hyperphosphorylation of retinoblastoma protein in the
      progression of malignant melanoma.
AB  - Mutation, absence or abnormal functioning of retinoblastoma protein are
      fundamental elements of uncontrolled growth in human cancer. In this study, we
      analyze the expression of retinoblastoma protein and phosphorylated
      retinoblastoma protein in melanocytic tumors in vivo. Real-time RT-PCR and
      immunohistochemistry (tissue microarrays and conventional histological sections)
      reveal that retinoblastoma protein is progressively upregulated in advanced and
      metastatic malignant melanomas in vivo. However, this increase is paralleled by
      increased retinoblastoma protein inactivation due to protein phosphorylation.
      Interestingly, retinoblastoma protein phosphorylation occurs not homogeneously,
      but with a 'growth zone'-related pattern. In superficial spreading melanomas a
      subepidermal-lateral maximum of phosphorylated retinoblastoma protein can be
      frequently observed. Accordingly, nodular vertically invasive melanomas are
      characterized by a strong staining of phosphorylated retinoblastoma protein in
      deep-dermal invading protrusions of the tumor. Furthermore, Kaplan-Meier analysis
      of 13 cases of advanced melanomas with long-time follow-up suggests a significant
      negative impact of retinoblastoma protein phosphorylation on survival of melanoma
      patients independent of tumor thickness. We conclude that the evaluation of
      phosphorylated retinoblastoma protein in melanocytic tumors could become a
      helpful adjunct in clinicopathological routine.

PMID- 15502805
TI  - Expression of aquaporins and PAX-2 compared to CD10 and cytokeratin 7 in renal
      neoplasms: a tissue microarray study.
AB  - Diagnostic use of antibodies against aquaporin water channel proteins and PAX-2,
      a nuclear transcription factor in renal development, was tested in 202 renal
      neoplasms, using tissue microarray technique. Immunohistochemistry for aquaporin
      1, aquaporin-2, PAX-2, CD10, and cytokeratin 7 was performed on 102 clear cell
      renal cell carcinomas, 44 papillary renal cell carcinomas (among them 34 type 1
      and 10 type 2), 24 chromophobe renal cell carcinomas, three collecting duct
      carcinomas (carcinomas of the collecting ducts of Bellini), and 29 oncocytomas.
      Aquaporin-1 expression was found in clear cell renal cell carcinomas and
      papillary renal cell carcinomas of both types (78 and 73%, respectively), but not
      in chromophobe renal cell carcinomas, collecting duct carcinomas, and
      oncocytomas. Aquaporin-2 expression was not seen in any of the tested tumors. PAX
      2 and CD10 was found in the majority of clear cell renal cell carcinomas (88 and
      85%, respectively) but only in few papillary renal cell carcinomas, chromophobe
      renal cell carcinomas and oncocytomas. Decrease or loss of aquaporin-1 and PAX-2
      was shown in higher grades compared to lower grades of clear cell renal cell
      carcinomas (P<0.0001 and <0.0245, respectively). Cytokeratin 7 was rarely seen in
      clear cell renal cell carcinomas, type 2 papillary renal cell carcinomas, and
      oncocytomas, but was found in the majority of type 1 papillary renal cell
      carcinomas (97.1%) and chromophobe renal cell carcinomas (88%). Aquaporin-1 and
      PAX-2 expression was found to correlate with nuclear grading for clear cell renal
      cell carcinomas but not for papillary renal cell carcinomas. No correlation of
      tumor stage and aquaporin-1 and PAX-2 expression was seen. Aquaporin-1 and PAX-2
      are reliable markers for clear cell renal cell carcinomas of lower grades but not
      for higher grades. CD10 expression remains stable, independent of nuclear
      grading.

PMID- 15502806
TI  - c-kit Expression in small cell carcinoma of the urinary bladder: prognostic and
      therapeutic implications.
AB  - The prognosis for small cell carcinoma of the urinary bladder is poor, and
      strategies for improved therapy are needed. Targeted therapy against the c-kit
      proto-oncogene has been successful in the management of gastrointestinal stromal
      tumor. We investigated the expression of c-kit in 52 cases of small cell
      carcinoma of the urinary bladder. Specimens with more than 10% of cells
      demonstrating strong membrane staining were considered to have positive
      immunostaining for c-kit. c-kit expression was detected in 21 of 52 specimens
      from these patients. Among the 21 specimens, seven had less than 10% staining,
      and were considered to be negative. Nine had 11-50% staining, and five had more
      than 50% staining. Overall, 14 of 52 (27%) small cell carcinomas of the urinary
      bladder were positive for c-kit expression. During a median follow-up of 11
      months, 60% of the patients died of bladder cancer. No association was found
      between c-kit expression and survival or other clinicopathologic parameters. Five
      year cancer-specific survivals for c-kit-positive and c-kit-negative tumors were
      9 and 15%, respectively (P=0.36). A significant proportion (27%) of small cell
      carcinomas of the urinary bladder expressed c-kit, suggesting that it may prove
      useful as a therapeutic target in small cell carcinoma of the urinary bladder.

PMID- 15502807
TI  - Prevalence of human papillomavirus DNA in various histological subtypes of
      cervical adenocarcinoma: a population-based study.
AB  - The role of human papilloma virus (HPV) infection in the development of cervical
      carcinoma is well established, however, the prevalence of HPV DNA in cervical
      adenocarcinoma varies from study to study. It appears to be caused by a number of
      factors, one of which is that cervical adenocarcinomas comprise a heterogeneous
      group of multiple subtypes. To clarify the impact of HPV infection on the
      development of cervical adenocarcinoma with diverse histological subtypes, we
      performed a population-based study in Korean women from 15 different institutes
      for the status of HPV infection in adenocarcinoma of uterine cervix. A total of
      432 cervical adenocarcinomas from 1997 to 2001 were reviewed and classified
      according to the modified WHO classification. For 135 cases, HPV typing was
      performed with HPV DNA chip (82 cases) and PCR HPV typing (53 cases), using
      formalin-fixed, paraffin-embedded archival tissue. The overall prevalence of HPV
      infection in cervical adenocarcinoma was 90%. The infection of HPV 16 and/or HPV
      18 accounted for 78% of HPV-positive adenocarcinomas. Multiple HPV types were
      found in 13% of the cases. The HPV DNA was rarely detected in minimal deviation
      adenocarcinoma. Interestingly, HPV 16 was a predominant type in endometrioid and
      villoglandular types, whereas HPV 16 and HPV 18 were detected with equal
      prevalence in other subtypes. In conclusion, HPV infection, mostly HPV 16 and HPV
      18, is highly associated with most of the cervical adenocarcinomas, whereas
      endometrioid and villoglandular type have a different pattern of HPV infection
      status. Minimal deviation adenocarcinoma does not seem to be related with HPV
      infection.

PMID- 15502808
TI  - Selected other problematic testicular and paratesticular lesions: rete testis
      neoplasms and pseudotumors, mesothelial lesions and secondary tumors.
AB  - The proximity and, in some instances, communication between several structures in
      the testis and paratestis (rete testis, epididymis, mesothelium, vestigial
      epithelium and paratesticular soft tissue) result in a plethora of interesting
      tumors and tumor-like lesions that together pose a formidable diagnostic
      challenge both because of their morphologic overlap and rarity. The occasional
      spread of tumors primarily at other sites to this region adds to the potential
      problem encountered. This review provides an overview of the pathology of
      nonmesenchymal paratesticular neoplasms and pseudotumors with a focus on the
      approach to tubulopapillary neoplasms for which diagnostic considerations may
      include carcinoma of the rete testis, malignant mesothelioma, ovarian-type
      epithelial tumors, epididymal carcinoma and metastatic carcinomas. The
      cornerstone of accurate characterization of these lesions is still a
      comprehensive, traditional clinicopathologic approach, clinical history (of
      another primary), gross examination (location) and routine light microscopy, but
      judicious incorporation of contemporary immunohistochemical markers may aid or in
      some instances be crucial in resolving the problems encountered.

PMID- 15502809
TI  - Sex cord-stromal tumors of the ovary and testis: their similarities and
      differences with consideration of selected problems.
AB  - Gonadal sex cord-stromal tumors contain some of the most morphologically
      interesting neoplasms of the gonads and these lead to many important issues in
      differential diagnosis. The pathology of these tumors is reviewed with emphasis
      on new information, similarities and differences in the two gonads, and
      diagnostic problems. Sertoli cell tumors occur in both gonads being more common
      in the testis where they usually exhibit a lobular pattern of hollow or solid
      tubules. In the ovary, tubular differentiation is usually the predominant feature
      but the lobulation typically seen in the testis is generally not as striking. One
      variant of Sertoli cell tumor, the large cell calcifying form, appears to be
      restricted to the male gonad and in contrast to other sex cord tumors is much
      more frequently bilateral and is associated in many cases with unusual clinical
      manifestations. In both sexes, patients with Peutz-Jeghers syndrome often have
      distinctive gonadal pathology. In females, it is in the form of the sex cord with
      annular tubules whereas in males, the lesion has features that are often
      intermediate between those of a sex cord tumor with annular tubules and a large
      cell calcifying Sertoli cell tumor. Sertoli-Leydig cell tumors are more
      morphologically diverse than pure Sertoli cell tumors and for practical purposes
      are an issue only in ovarian pathology being exceptionally rare in the testis.
      The classification proposed by Meyer into well, intermediate, and poor
      differentiation, remains important prognostically. More recently, heterologous
      and retiform differentiation has been described. Heterologous tumors most often
      contain mucinous epithelium, sometimes with small foci of carcinoid or less
      commonly, and generally in poorly differentiated neoplasms, rhabdomyosarcoma or
      fetal-type cartilage. Such tumors should be distinguished from pure sarcomas and
      teratomas. The retiform neoplasms, which tend to occur in young females, may
      mimic serous borderline tumors or even serous carcinomas. Granulosa cell tumors
      are much more common in females and in both gonads are divided into adult and
      juvenile forms. In females, granulosa cell tumors and other sex cord tumors may
      have markedly bizarre nuclei potentially leading to overdiagnosis as more
      malignant neoplasms. The juvenile granulosa cell tumor of the testis tends to
      occur in the first 6 months of life and should be carefully distinguished from
      the yolk sac tumor of the testis, which usually occurs in a slightly older age
      group. Occasional sex cord-stromal tumors cannot be readily categorized into the
      Sertoli or granulosa families and are diagnosed as sex cord-stromal tumors
      unclassified. In females, this is a relatively common placement for a neoplasm in
      a pregnant patient. Unclassified tumors are overall more common in males and may
      entrap residual normal germ cells potentially leading to the erroneous placement
      of the tumor in the category of a mixed germ cell sex cord-stromal tumor. From
      the practical viewpoint, the most helpful immunohistochemical findings are the
      negative staining of sex cord tumors for epithelial membrane antigen, and
      positive staining for inhibin and calretinin, findings that are converse to those
      seen in endometrioid carcinomas of the ovary, which commonly have formations that
      simulate sex cord tumors.

PMID- 15502810
TI  - p16INK4A and p14ARF expression pattern by immunohistochemistry in human
      papillomavirus-related cervical neoplasia.
AB  - Human papillomavirus is known to play an important etiological role in the
      genesis of cervical cancer, but only a very small proportion of infected women
      develop invasive cervical cancer. The purpose of cervical cancer prevention is
      early diagnosis of its precursors. The molecular detection of human
      papillomavirus DNA as a diagnostic test to cervical carcinogenesis gave a low
      positive predictive value as compared to the use of biomarkers. p16INK4A and
      possibly p14ARF have been proposed as putative surrogate biomarkers that would
      allow identification of dysplastic cervical epithelia. Serial consecutive
      biopsies representing normal cervical epithelium to cervical intraepithelial
      neoplasia and/or invasive cervical cancer were stained with immunohistochemistry
      for p16INK4A, p14ARF and proliferating cell nuclear antigen. The positive rates
      of these markers were significantly higher in cervical intraepithelial neoplasia
      and in squamous cell carcinoma than in normal cervix (P<0.01). No significant
      difference was noted between lesions progressing from cervical intraepithelial
      neoplasia to squamous cell carcinoma for both p16INK4A and p14ARF expression
      (P>0.05). For both biomarkers, nuclear staining was predominantly seen. However,
      the cytoplasmic stain of p16INK4A increased with disease progression and the
      pattern of expression varied between different tumors and its location within the
      lesion. Both nuclear and cytoplasmic staining with p16INK4A and p14ARF of
      affected epithelial cells were considered positive. In the adjacent normal tissue
      to cervical neoplasia, the positive rates of p16INK4A, p14ARF and proliferating
      cell nuclear antigen expression were higher than those found distant to these
      lesions but the findings did not reach statistical significance. No correlation
      was seen between the human papillomavirus types detected and the expression of
      p16INK4a and p14ARF. In conclusion, overexpression of p16INK4A and p14ARF act as
      potential biomarkers for cervical cancer progression from premalignant lesions.

PMID- 15502811
TI  - In vivo and ex vivo virtual biopsy of the liver with near-infrared, reflectance
      confocal microscopy.
AB  - The assessment of liver architecture is an essential part of the understanding of
      its physiology and pathology. Current fluorescence confocal microscopy methods
      face numerous drawbacks, such as cytotoxicity, quenching effect, potential
      negative ino- and chrono-tropic effects and leaking of fluorescent agents through
      the sinusoid fenestrations. The recently developed, near-infrared reflectance
      confocal microscopy allows high-resolution optical sectioning through intact
      tissues, without employing fluorescent stains, while contrast between structures
      is provided by the natural refractivity of the tissue. The aim of this study is
      to assess the utility of near-infrared reflectance confocal microscopy in the
      evaluation of the hepatic microscopic architecture in vivo and ex vivo. Rat
      livers were noninvasively examined in vivo and ex vivo with near-infrared
      reflectance confocal microscopy. Two experimental contrast agents were
      subsequently used to enhance particular structures. Parenchymal and vascular
      structures are readily identified, as well as some intracellular details.
      Differences between in vivo and ex vivo states were also observed. The use of
      contrast agents also highlights certain morphologic structures. In conclusion,
      near-infrared reflectance confocal microscopy stands as a useful adjunct
      technique to the study of hepatic parenchyma offering details equivalent to, if
      not surpassing traditional light microscopy.

PMID- 15502812
TI  - Molecular model for a complete clathrin lattice from electron cryomicroscopy.
AB  - Clathrin-coated vesicles are important vehicles of membrane traffic in cells. We
      report the structure of a clathrin lattice at subnanometre resolution, obtained
      from electron cryomicroscopy of coats assembled in vitro. We trace most of the
      1,675-residue clathrin heavy chain by fitting known crystal structures of two
      segments, and homology models of the rest, into the electron microscopy density
      map. We also define the position of the central helical segment of the light
      chain. A helical tripod, the carboxy-terminal parts of three heavy chains,
      projects inward from the vertex of each three-legged clathrin triskelion, linking
      that vertex to 'ankles' of triskelions centred two vertices away. Analysis of
      coats with distinct diameters shows an invariant pattern of contacts in the
      neighbourhood of each vertex, with more variable interactions along the extended
      parts of the triskelion 'legs'. These invariant local interactions appear to
      stabilize the lattice, allowing assembly and uncoating to be controlled by events
      at a few specific sites.

PMID- 15502813
TI  - Structure of an auxilin-bound clathrin coat and its implications for the
      mechanism of uncoating.
AB  - Clathrin-coated pits invaginate from specific membrane compartments and pinch off
      as coated vesicles. These vesicles then uncoat rapidly once released. The Hsc70
      molecular chaperone effects the uncoating reaction, and is guided to appropriate
      locations on clathrin lattices by the J-domain-containing co-chaperone molecule
      auxilin. This raises the question of how a local event such as ATP hydrolysis by
      Hsc70 can catalyse a global disassembly. Here, we have used electron
      cryomicroscopy to determine 12-A-resolution structures of in-vitro-assembled
      clathrin coats in association with a carboxy-terminal fragment of auxilin that
      contains both the clathrin-binding region and the J domain. We have located the
      auxilin fragment by computing differences between these structures and those
      lacking auxilin (described in an accompanying paper). Auxilin binds within the
      clathrin lattice near contacts between an inward-projecting C-terminal helical
      tripod and the crossing of two 'ankle' segments; it also contacts the terminal
      domain of yet another clathrin 'leg'. It therefore recruits Hsc70 to the
      neighbourhood of a set of critical interactions. Auxilin binding produces a local
      change in heavy-chain contacts, creating a detectable global distortion of the
      clathrin coat. We propose a mechanism by which local destabilization of the
      lattice promotes general uncoating.

PMID- 15502814
TI  - In the platypus a meiotic chain of ten sex chromosomes shares genes with the bird
      Z and mammal X chromosomes.
AB  - Two centuries after the duck-billed platypus was discovered, monotreme chromosome
      systems remain deeply puzzling. Karyotypes of males, or of both sexes, were
      claimed to contain several unpaired chromosomes (including the X chromosome) that
      form a multi-chromosomal chain at meiosis. Such meiotic chains exist in plants
      and insects but are rare in vertebrates. How the platypus chromosome system works
      to determine sex and produce balanced gametes has been controversial for decades.
      Here we demonstrate that platypus have five male-specific chromosomes (Y
      chromosomes) and five chromosomes present in one copy in males and two copies in
      females (X chromosomes). These ten chromosomes form a multivalent chain at male
      meiosis, adopting an alternating pattern to segregate into XXXXX-bearing and
      YYYYY-bearing sperm. Which, if any, of these sex chromosomes bears one or more
      sex-determining genes remains unknown. The largest X chromosome, with homology to
      the human X chromosome, lies at one end of the chain, and a chromosome with
      homology to the bird Z chromosome lies near the other end. This suggests an
      evolutionary link between mammal and bird sex chromosome systems, which were
      previously thought to have evolved independently.

PMID- 15502815
TI  - Photoswitchable cyan fluorescent protein for protein tracking.
AB  - In recent years diverse photolabeling techniques using green fluorescent protein
      (GFP)-like proteins have been reported, including photoactivatable PA-GFP,
      photoactivatable protein Kaede, the DsRed 'greening' technique and kindling
      fluorescent proteins. So far, only PA-GFP, which is monomeric and gives 100-fold
      fluorescence contrast, could be applied for protein tracking. Here we describe a
      dual-color monomeric protein, photoswitchable cyan fluorescent protein (PS-CFP).
      PS-CFP is capable of efficient photoconversion from cyan to green, changing both
      its excitation and emission spectra in response to 405-nm light irradiation.
      Complete photoactivation of PS-CFP results in a 1,500-fold increase in the green
      to-cyan fluorescence ratio, making it the highest-contrast monomeric
      photoactivatable fluorescent protein described to date. We used PS-CFP as a
      photoswitchable tag to study trafficking of human dopamine transporter in living
      cells. At moderate excitation intensities, PS-CFP can be used as a pH-stable cyan
      label for protein tagging and fluorescence resonance energy transfer
      applications.

PMID- 15502816
TI  - Engineered T-cell receptor tetramers bind MHC-peptide complexes with high
      affinity.
AB  - In this study we extend tetramerization technology to T-cell receptors (TCRs). We
      identified TCR alpha beta pairs in the absence of accessory molecules, ensuring
      isolation of high-affinity TCRs that maintain stable binding characteristics
      after tetramerization. Subtle changes in cognate peptide levels bound to the
      class I molecule were accurately reflected by parallel changes in the mean
      fluorescence intensity of cells that bound TCR tetramers, allowing us to
      accurately assess the binding affinity of a panel of peptides to major
      histocompatibility complex (MHC) class I. Using a TCR tetramer specific for the
      Mamu-A(*)01 allele, we identified animals expressing this restricting class I
      allele from a large cohort of outbred rhesus macaques. TCR tetramers should
      facilitate analysis of the MHC-peptide interface and, more generally, the design
      of immunotherapeutics and vaccines.

PMID- 15502817
TI  - Antidote-mediated control of an anticoagulant aptamer in vivo.
AB  - Patient safety and treatment outcome could be improved if physicians could
      rapidly control the activity of therapeutic agents in their patients. Antidote
      control is the safest way to regulate drug activity, because unlike rapidly
      clearing drugs, control of the drug activity is independent of underlying patient
      physiology and co-morbidities. Until recently, however, there was no general
      method to discover antidote-controlled drugs. Here we demonstrate that the
      activity and side effects of a specific class of drugs, called aptamers, can be
      controlled by matched antidotes in vivo. The drug, an anticoagulant aptamer,
      systemically induces anticoagulation in pigs and inhibits thrombosis in murine
      models. The antidote rapidly reverses anticoagulation engendered by the drug, and
      prevents drug-induced bleeding in surgically challenged animals. These results
      demonstrate that rationally designed drug-antidote pairs can be generated to
      provide control over drug activities in animals.

PMID- 15502818
TI  - Quantitative analysis of allosteric drug-protein binding by biointeraction
      chromatography.
AB  - Allosteric interactions are important in many biological processes. They occur
      when the interactions of one substance with a binding agent changes the
      interactions of a second substance with the same agent at a separate site. Such
      interactions are often observed during the binding of drugs to blood proteins
      such as human serum albumin (HSA). Most previous studies of allosteric
      interactions have involved only qualitative observations of increased or
      decreased binding. In this study, we present an approach for quantitatively
      characterizing such allosteric effects using protein columns. The method is used
      to examine the interactions of ibuprofen/S-lorazepam acetate, S-oxazepam
      hemisuccinate/R-oxazepam hemisuccinate, and L-tryptophan/phenytoin during their
      binding to HSA. This approach can be applied to other receptors or biopolymers
      and can be used to independently examine the effects of two competing agents
      during an allosteric interaction.

PMID- 15502819
TI  - Gas-inducible transgene expression in mammalian cells and mice.
AB  - We describe the design and detailed characterization of a gas-inducible transgene
      control system functional in different mammalian cells, mice and prototype
      biopharmaceutical manufacturing. The acetaldehyde-inducible AlcR-P(alcA)
      transactivator-promoter interaction of the Aspergillus nidulans ethanol
      catabolizing regulon was engineered for gas-adjustable transgene expression in
      mammalian cells. Fungal AlcR retained its transactivation characteristics in a
      variety of mammalian cell lines and reversibly adjusted transgene transcription
      from chimeric mammalian promoters (P(AIR)) containing P(alcA)-derived operators
      in a gaseous acetaldehyde-dependent manner. Mice implanted with microencapsulated
      cells engineered for acetaldehyde-inducible regulation (AIR) of the human
      glycoprotein secreted placental alkaline phosphatase showed adjustable serum
      phosphatase levels after exposure to different gaseous acetaldehyde
      concentrations. AIR-controlled interferon-beta production in transgenic CHO-K1
      derived serum-free suspension cultures could be modulated by fine-tuning inflow
      and outflow of acetaldehyde-containing gas during standard bioreactor operation.
      AIR technology could serve as a tool for therapeutic transgene dosing as well as
      biopharmaceutical manufacturing.

PMID- 15502820
TI  - Nitric oxide induces coupling of mitochondrial signalling with the endoplasmic
      reticulum stress response.
AB  - Nitric oxide (NO) is a pleiotropic signalling molecule that binds to cytochrome c
      oxidase (complex IV) reversibly and in competition with oxygen. This action of NO
      has both physiological and pathophysiological consequences. Here we report that
      endogenously generated NO, which disrupts the respiratory chain, may cause
      changes in mitochondrial calcium flux. This induces cleavage of the endoplasmic
      reticulum (ER) stress-regulated transcription factor p90 ATF6 into an active p50
      form. Cleavage depends on a calcium-dependent serine protease through a regulated
      intramembrane proteolysis (RIP) process. p50 ATF6 then translocates to the
      nucleus to upregulate expression of the ER-resident molecular chaperone, glucose
      regulated protein 78 (Grp78). The increase in Grp78 provides significant
      cytoprotection against toxic agents, including thapsigargin, a selective ER
      calcium-ATPase inhibitor. Cytoprotection is abolished after treatment with
      cyclosporin A (CsA), which disrupts mitochondrial calcium signalling, or with the
      calcium chelator BAPTA-AM. The NO-mediated ER stress response is diminished in
      rho(0) cells devoid of mitochondrial DNA, consistent with our evidence that NO
      dependent mitochondrial disruption is coupled to the ER stress response.

PMID- 15502821
TI  - A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer
      kinetochore protein Zwint-1.
AB  - Defects in kinetochore proteins often lead to aneuploidy and cancer. Mis12-Mtw1
      is a conserved, essential kinetochore protein family. Here, we show that a Mis12
      core complex exists in Schizosaccharomyces pombe and human cells. Nine
      polypeptides bind to human hMis12; two of these, HEC1 and Zwint-1, are authentic
      kinetochore proteins. Four other human proteins of unknown function (c20orf172,
      DC8, PMF1 and KIAA1570) correspond to yeast Mis12-Mtw1 complex components and are
      shown to be required for chromosome segregation in HeLa cells using RNA
      interference (RNAi). Surprisingly, hMis12 also forms a stable complex with the
      centromeric heterochromatin components HP1alpha and HP1gamma. Double HP1 RNAi
      abolishes kinetochore localization of hMis12 and DC8. Therefore, centromeric HP1
      may be the base to anchor the hMis12 core complex that is enriched with coiled
      coils and extends to outer Zwint-1 during mitosis.

PMID- 15502822
TI  - Mapping the dynamic organization of the nuclear pore complex inside single living
      cells.
AB  - Most cellular activities are executed by multi-protein complexes that form the
      basic functional modules of their molecular machinery. Proteomic approaches can
      provide an evermore detailed picture of their composition, but do not reveal how
      these machines are organized dynamically to accomplish their biological function.
      Here, we present a method to determine the dissociation rates of protein subunits
      from complexes that have a traceable localization inside single living cells. As
      a case study, we systematically analysed the dynamic organization of vertebrate
      nuclear pore complexes (NPCs), large supramolecular complexes of about 30
      different polypeptides. NPC components exhibited a wide range of residence times
      covering five orders of magnitude from seconds to days. We found the central
      parts of the NPC to be very stable, consistent with a function as a structural
      scaffold, whereas more peripheral components exhibited more dynamic behaviour,
      suggesting adaptor as well as regulatory functions. The presented strategy can be
      applied to many multi-protein complexes and will help to characterize the dynamic
      behaviour of complex networks of proteins in live cells.

PMID- 15502823
TI  - Actin is part of pre-initiation complexes and is necessary for transcription by
      RNA polymerase II.
AB  - Actin is abundant in the nucleus and has been implicated in transcription;
      however, the nature of this involvement has not been established. Here we
      demonstrate that beta-actin is critically involved in transcription because
      antibodies directed against beta-actin, but not muscle actin, inhibited
      transcription in vivo and in vitro. Chromatin immunoprecipitation assays
      demonstrated the recruitment of actin to the promoter region of the interferon
      gamma-inducible MHC2TA gene as well as the interferon-alpha-inducible G1P3 gene.
      Further investigation revealed that actin and RNA polymerase II co-localize in
      vivo and also co-purify. We employed an in vitro system with purified nuclear
      components to demonstrate that antibodies to beta-actin block the initiation of
      transcription. This assay also demonstrates that beta-actin stimulates
      transcription by RNA polymerase II. Finally, DNA-binding experiments established
      the presence of beta-actin in pre-initiation complexes and also showed that the
      depletion of actin prevented the formation of pre-initiation complexes. Together,
      these data suggest a fundamental role for actin in the initiation of
      transcription by RNA polymerase II.

PMID- 15502824
TI  - Secretory traffic triggers the formation of tubular continuities across Golgi sub
      compartments.
AB  - The organization of secretory traffic remains unclear, mainly because of the
      complex structure and dynamics of the secretory pathway. We have thus studied a
      simplified system, a single synchronized traffic wave crossing an individual
      Golgi stack, using electron tomography. Endoplasmic-reticulum-to-Golgi carriers
      join the stack by fusing with cis cisternae and induce the formation of
      intercisternal tubules, through which they redistribute their contents throughout
      the stack. These tubules seem to be pervious to Golgi enzymes, whereas Golgi
      vesicles are depleted of both enzymes and cargo. Cargo then traverses the stack
      without leaving the cisternal lumen. When cargo exits the stack, intercisternal
      connections disappear. These findings provide a new view of secretory traffic
      that includes dynamic intercompartment continuities as key players.

PMID- 15502825
TI  - Infantile-onset symptomatic epilepsy syndrome caused by a homozygous loss-of
      function mutation of GM3 synthase.
AB  - We identified an autosomal recessive infantile-onset symptomatic epilepsy
      syndrome associated with developmental stagnation and blindness. Assuming a
      founder effect in a large Old Order Amish pedigree, we carried out a genome-wide
      screen for linkage and identified a single region of homozygosity on chromosome
      2p12-p11.2 spanning 5.1 cM (maximum lod score of 6.84). We sequenced genes in the
      region and identified a nonsense mutation in SIAT9, which is predicted to result
      in the premature termination of the GM3 synthase enzyme (also called
      lactosylceramide alpha-2,3 sialyltransferase). GM3 synthase is a member of the
      sialyltransferase family and catalyzes the initial step in the biosynthesis of
      most complex gangliosides from lactosylceramide. Biochemical analysis of plasma
      glycosphingolipids confirmed that affected individuals lack GM3 synthase
      activity, as marked by a complete lack of GM3 ganglioside and its biosynthetic
      derivatives and an increase in lactosylceramide and its alternative derivatives.
      Although the relationship between defects in ganglioside catabolism and a range
      of lysosomal storage diseases is well documented, this is the first report, to
      our knowledge, of a disruption of ganglioside biosynthesis associated with human
      disease.

PMID- 15502826
TI  - Targeted gene alteration in Caenorhabditis elegans by gene conversion.
AB  - Now that some genomes have been completely sequenced, the ability to direct
      specific mutations into genomes is particularly desirable. Here we present a
      method to create mutations in the Caenorhabditis elegans genome efficiently
      through transgene-directed, transposon-mediated gene conversion. Engineered
      deletions targeted into two genes show that the frequency of obtaining the
      desired mutation was higher using this approach than using standard transposon
      insertion-deletion approaches. We also targeted an engineered green fluorescent
      protein insertion-replacement cassette to one of these genes, thereby confirming
      that custom alleles of different types can be created in vitro to make the
      corresponding mutations in vivo. This approach should also be applicable to
      heterologous transposons in C. elegans and other organisms, including
      vertebrates.

PMID- 15502827
TI  - X-linked inheritance of Fanconi anemia complementation group B.
AB  - Fanconi anemia is an autosomal recessive syndrome characterized by diverse
      clinical symptoms, hypersensitivity to DNA crosslinking agents, chromosomal
      instability and susceptibility to cancer. Fanconi anemia has at least 11
      complementation groups (A, B, C, D1, D2, E, F, G, I, J, L); the genes mutated in
      8 of these have been identified. The gene BRCA2 was suggested to underlie
      complementation group B, but the evidence is inconclusive. Here we show that the
      protein defective in individuals with Fanconi anemia belonging to complementation
      group B is an essential component of the nuclear protein 'core complex'
      responsible for monoubiquitination of FANCD2, a key event in the DNA-damage
      response pathway associated with Fanconi anemia and BRCA. Unexpectedly, the gene
      encoding this protein, FANCB, is localized at Xp22.31 and subject to X-chromosome
      inactivation. X-linked inheritance has important consequences for genetic
      counseling of families with Fanconi anemia belonging to complementation group B.
      Its presence as a single active copy and essentiality for a functional Fanconi
      anemia-BRCA pathway make FANCB a potentially vulnerable component of the cellular
      machinery that maintains genomic integrity.

PMID- 15502828
TI  - Exhaustive allelic transmission disequilibrium tests as a new approach to genome
      wide association studies.
AB  - Genome-wide disease-association mapping has been heralded as the study design of
      the next generation, but the lack of analytical methods to use genotype data
      fully is a large stumbling block. Here we describe an algorithm and statistical
      method that efficiently and exhaustively exploits haplotype information by
      subjecting alleles (a marker or contiguous sets of markers) from sliding windows
      of all sizes to transmission disequilibrium tests. By applying our method to
      simulated data and to Hirschsprung disease, we show that it can detect both
      common and rare disease variants of small effect. These results show that the
      theoretical benefits of genome-wide association studies are at last realizable.

PMID- 15502829
TI  - Mechanisms and convergence of compensatory evolution in mammalian mitochondrial
      tRNAs.
AB  - The function of protein and RNA molecules depends on complex epistatic
      interactions between sites. Therefore, the deleterious effect of a mutation can
      be suppressed by a compensatory second-site substitution. In relating a list of
      86 pathogenic mutations in human tRNAs encoded by mitochondrial genes to the
      sequences of their mammalian orthologs, we noted that 52 pathogenic mutations
      were present in normal tRNAs of one or several nonhuman mammals. We found at
      least five mechanisms of compensation for 32 pathogenic mutations that destroyed
      a Watson-Crick pair in one of the four tRNA stems: restoration of the affected
      Watson-Crick interaction (25 cases), strengthening of another pair (4 cases),
      creation of a new pair (8 cases), changes of multiple interactions in the
      affected stem (11 cases) and changes involving the interaction between the loop
      and stem structures (3 cases). A pathogenic mutation and its compensating
      substitution are fixed in a lineage in rapid succession, and often a compensatory
      interaction evolves convergently in different clades. At least 10%, and perhaps
      as many as 50%, of all nucleotide substitutions in evolving mammalian tRNAs
      participate in such interactions, indicating that the evolution of tRNAs proceeds
      along highly epistatic fitness ridges.

PMID- 15502830
TI  - Disruption of Erk-dependent type I interferon induction breaks the myxoma virus
      species barrier.
AB  - Myxoma virus, a member of the poxvirus family, causes lethal infection only in
      rabbits, but the mechanism underlying the strict myxoma virus species barrier is
      not known. Here we show that myxoma virus infection of primary mouse embryo
      fibroblasts elicited extracellular signal-regulated kinase (Erk) signaling, which
      was integrated to interferon regulatory factor 3 activation and type I interferon
      induction. We further show that Erk inactivation or disruption of interferon
      signaling mediated by the transcription factor STAT1 broke the cellular blockade
      to myxoma virus multiplication. Moreover, STAT1 deficiency rendered mice highly
      susceptible to lethal myxoma virus infection. Thus, the Erk-interferon-STAT1
      signaling cascade elicited by myxoma virus in nonpermissive primary mouse embryo
      fibroblasts mediates an innate cellular barrier to poxvirus infection.

PMID- 15502831
TI  - Lock-and-key effect in the surface diffusion of large organic molecules probed by
      STM.
AB  - A nanoscale understanding of the complex dynamics of large molecules at surfaces
      is essential for the bottom-up design of molecular nanostructures. Here we show
      that we can change the diffusion coefficient of the complex organic molecule
      known as Violet Lander (VL, C(108)H(104)) on Cu(110) by two orders of magnitude
      by using the STM at low temperatures to switch between two adsorption
      configurations that differ only in the molecular orientation with respect to the
      substrate lattice. From an interplay with molecular dynamics simulations, we
      interpret the results within a lock-and-key model similar to the one driving the
      recognition between biomolecules: the molecule (key) is immobilized only when its
      orientation is such that the molecular shape fits the atomic lattice of the
      surface (lock); otherwise the molecule is highly mobile.

PMID- 15502832
TI  - Flash welding of conducting polymer nanofibres.
AB  - The absorption of light by a material generates heat through non-radiative energy
      dissipation and exothermic photochemical reactions. In nanostructured materials,
      the heat generated through photothermal processes will be confined within the
      individual nanostructures when heat transfer to neighbouring nanostructures and
      the environment is slow. This leads to unprecedented photothermal effects that
      cannot be observed in bulk materials, especially when a strong, pulsed light
      source is used. Here we demonstrate an enhanced photothermal phenomenon with
      conducting polymer nanofibres in which a camera flash causes instantaneous
      welding. Under flash irradiation, polyaniline nanofibres 'melt' to form a smooth
      and continuous film from an originally random network of nanofibres. This
      photothermal effect can be used to form asymmetric nanofibre films, to melt-blend
      polymer-polymer nanocomposites rapidly and to photo-pattern polymer nanofibre
      films.

PMID- 15502833
TI  - Amorphous silicon exhibits a glass transition.
AB  - Amorphous silicon is a semiconductor with a lower density than the metallic
      silicon liquid. It is widely believed that the amorphous-liquid transition is a
      first-order melting transition. In contrast to this, recent computer simulations
      and the experimental observation of pressure-induced amorphization of nanoporous
      silicon have revived the idea of an underlying liquid-liquid phase transition
      implying the existence of a low-density liquid and its glass transition to the
      amorphous solid. Here we demonstrate that during irradiation with high-energy
      heavy ions amorphous silicon deforms plastically in the same way as conventional
      glasses. This behaviour provides experimental evidence for the existence of the
      low-density liquid. The glass transition temperature for a timescale of 10
      picoseconds is estimated to be about 1,000 K. Our results support the idea of
      liquid polymorphism as a general phenomenon in tetrahedral networks.

PMID- 15502834
TI  - Electrical spin injection from an n-type ferromagnetic semiconductor into a III-V
      device heterostructure.
AB  - The use of carrier spin in semiconductors is a promising route towards new device
      functionality and performance. Ferromagnetic semiconductors (FMSs) are promising
      materials in this effort. An n-type FMS that can be epitaxially grown on a common
      device substrate is especially attractive. Here, we report electrical injection
      of spin-polarized electrons from an n-type FMS, CdCr(2)Se(4), into an AlGaAs/GaAs
      based light-emitting diode structure. An analysis of the electroluminescence
      polarization based on quantum selection rules provides a direct measure of the
      sign and magnitude of the injected electron spin polarization. The sign reflects
      minority rather than majority spin injection, consistent with our density
      functional-theory calculations of the CdCr(2)Se(4) conduction-band edge. This
      approach confirms the exchange-split band structure and spin-polarized carrier
      population of an FMS, and demonstrates a litmus test for these FMS hallmarks that
      discriminates against spurious contributions from magnetic precipitates.

PMID- 15502835
TI  - Surface grafting of artificial joints with a biocompatible polymer for preventing
      periprosthetic osteolysis.
AB  - Periprosthetic osteolysis-bone loss in the vicinity of a prosthesis-is the most
      serious problem limiting the longevity of artificial joints. It is caused by bone
      resorptive responses to wear particles originating from the articulating surface.
      This study investigated the effects of graft polymerization of our original
      biocompatible phospholipid polymer 2-methacryloyloxyethyl phosphorylcholine (MPC)
      onto the polyethylene surface. Mechanical studies using a hip-joint simulator
      revealed that the MPC grafting markedly decreased the friction and the amount of
      wear. Osteoclastic bone resorption induced by subperiosteal injection of
      particles onto mouse calvariae was abolished by the MPC grafting on particles.
      MPC-grafted particles were shown to be biologically inert by culture systems with
      respect to phagocytosis and resorptive cytokine secretion by macrophages,
      subsequent expression of receptor activator of NF-kappaB ligand in osteoblasts,
      and osteoclastogenesis from bone marrow cells. From the mechanical and biological
      advantages, we believe that our approach will make a major improvement in
      artificial joints by preventing periprosthetic osteolysis.

PMID- 15502836
TI  - Composite mesostructures by nano-confinement.
AB  - In a physically confined environment, interfacial interactions, symmetry
      breaking, structural frustration and confinement-induced entropy loss can play
      dominant roles in determining molecular organization. Here we present a
      systematic study of the confined assembly of silica-surfactant composite
      mesostructures within cylindrical nanochannels of varying diameters. Using
      exactly the same precursors and reaction conditions that form the two-dimensional
      hexagonal SBA-15 mesostructured thin film, unprecedented silica mesostructures
      with chiral mesopores such as single- and double-helical geometries spontaneously
      form inside individual alumina nanochannels. On tightening the degree of
      confinement, a transition is observed in the mesopore morphology from a coiled
      cylindrical to a spherical cage-like geometry. Self-consistent field calculations
      carried out to account for the observed mesostructures accord well with
      experiment. The mesostructures produced by confined syntheses are useful as
      templates for fabricating highly ordered mesostructured nanowires and nanowire
      arrays.

PMID- 15502837
TI  - Alloy catalysts designed from first principles.
AB  - The rational design of pure and alloy metal catalysts from fundamental principles
      has the potential to yield catalysts of greatly improved activity and
      selectivity. A promising area of research concerns the role that near-surface
      alloys (NSAs) can play in endowing surfaces with novel catalytic properties. NSAs
      are defined as alloys wherein a solute metal is present near the surface of a
      host metal in concentrations different from the bulk; here we use density
      functional theory calculations to introduce a new class of these alloys that can
      yield superior catalytic behaviour for hydrogen-related reactions. Some of these
      NSAs bind atomic hydrogen (H) as weakly as the noble metals (Cu, Au) while, at
      the same time, dissociating H(2) much more easily. This unique set of properties
      may permit these alloys to serve as low-temperature, highly selective catalysts
      for pharmaceuticals production and as robust fuel-cell anodes.

PMID- 15502838
TI  - Periodically ordered nanoscale islands and mesoporous films composed of
      nanocrystalline multimetallic oxides.
AB  - Innovative strategies to produce well-defined nanoparticles and other
      nanostructures such as nanofibres, quantum wells and mesoporous materials have
      revitalized materials science for the potential benefit to society. Here, we
      report a controlled process, involving soft-chemistry-based deposition, template
      assisted mesostructured growth, and tuned annealing conditions that allows the
      preparation of ordered mesoporous crystalline networks and mesostructured nano
      island single layers, composed of multicationic metal oxides having perovskite,
      tetragonal or ilmenite structures. This strategy to obtain meso-organized multi
      metal-oxide nanocrystalline films (M(3)NF) bridges the gap between conventional
      mesoporous materials and the remarkable properties of crystalline ternary or
      quaternary metallic oxides. Nanocrystalline mesoporous films with controlled wall
      thickness (10-20 nm) of dielectric SrTiO(3), photoactive MgTa(2)O(6) or
      ferromagnetic semi-conducting Co(x)Ti(1-x)O(2-x) were prepared by evaporation
      induced self-assembly (EISA) using a specially designed non-ionic block-copolymer
      template. A tuned thermal treatment of the mesoporous films permits the transfer
      of the wall structure into nanocrystallites, with all tectonic units being
      tightly incorporated into mechanically stable ordered tri- or bidimensional
      nanocrystalline networks. This methodology should allow multifunctionalization,
      miniaturization and integration during development of devices such as smart
      sensors and actuators, better-performing photocatalysts, and fast electrochromic
      devices. On the other hand, organized arrays of dispersed ferromagnetic or
      ferroelectric nanoparticles are promising materials for spintronics and for
      cheap, non-volatile 'flash' memories.

PMID- 15502839
TI  - Recombinant modified vaccinia virus Ankara expressing antigen 85A boosts BCG
      primed and naturally acquired antimycobacterial immunity in humans.
AB  - Protective immunity against Mycobacterium tuberculosis depends on the generation
      of a T(H)1-type cellular immune response, characterized by the secretion of
      interferon-gamma (IFN-gamma) from antigen-specific T cells. The induction of
      potent cellular immune responses by vaccination in humans has proven difficult.
      Recombinant viral vectors, especially poxviruses and adenoviruses, are
      particularly effective at boosting previously primed CD4(+) and CD8(+) T-cell
      responses against a number of intracellular pathogens in animal studies. In the
      first phase 1 study of any candidate subunit vaccine against tuberculosis,
      recombinant modified vaccinia virus Ankara (MVA) expressing antigen 85A (MVA85A)
      was found to induce high levels of antigen-specific IFN-gamma-secreting T cells
      when used alone in bacille Calmette-Guerin (BCG)-naive healthy volunteers. In
      volunteers who had been vaccinated 0.5-38 years previously with BCG,
      substantially higher levels of antigen-specific IFN-gamma-secreting T cells were
      induced, and at 24 weeks after vaccination these levels were 5-30 times greater
      than in vaccinees administered a single BCG vaccination. Boosting vaccinations
      with MVA85A could offer a practical and efficient strategy for enhancing and
      prolonging antimycobacterial immunity in tuberculosis-endemic areas.

PMID- 15502840
TI  - Short interfering RNA (siRNA) targeting the Lyn kinase induces apoptosis in
      primary, and drug-resistant, BCR-ABL1(+) leukemia cells.
AB  - We studied the effects of Lyn ablation on the survival of drug-resistant chronic
      myelogenous leukemia (CML) blast crisis cells using siRNA. Lyn siRNA reduced Lyn
      protein in both normal hematopoietic cells and BCR-ABL1-expressing (BCR-ABL1(+))
      blasts by 80-95%. Within 48 h, siRNA-treated BCR-ABL1(+) blasts underwent
      apoptosis, whereas normal cells remained viable. This increased dependence on Lyn
      signaling for BCR-ABL1(+) blast survival provides the basis for rational
      treatment of drug-resistant CML blast crisis, particularly when lymphoid in
      nature.

PMID- 15502841
TI  - Donor-specific B-cell tolerance after ABO-incompatible infant heart
      transplantation.
AB  - Although over 50 years have passed since its first laboratory description,
      intentional induction of immune tolerance to foreign antigens has remained an
      elusive clinical goal. We previously reported that the requirement for ABO
      compatibility in heart transplantation is not applicable to infants. Here, we
      show that ABO-incompatible heart transplantation during infancy results in
      development of B-cell tolerance to donor blood group A and B antigens. This
      mimics animal models of neonatal tolerance and indicates that the human infant is
      susceptible to intentional tolerance induction. Tolerance in this setting occurs
      by elimination of donor-reactive B lymphocytes and may be dependent upon
      persistence of some degree of antigen expression. These findings suggest that
      intentional exposure to nonself A and B antigens may prolong the window of
      opportunity for ABO-incompatible transplantation, and have profound implications
      for clinical research on tolerance induction to T-independent antigens relevant
      to xenotransplantation.

PMID- 15502842
TI  - The RAB25 small GTPase determines aggressiveness of ovarian and breast cancers.
AB  - High-density array comparative genomic hybridization (CGH) showed amplification
      of chromosome 1q22 centered on the RAB25 small GTPase, which is implicated in
      apical vesicle trafficking, in approximately half of ovarian and breast cancers.
      RAB25 mRNA levels were selectively increased in stage III and IV serous
      epithelial ovarian cancers compared to other genes within the amplified region,
      implicating RAB25 as a driving event in the development of the amplicon.
      Increased DNA copy number or RNA level of RAB25 was associated with markedly
      decreased disease-free survival or overall survival in ovarian and breast
      cancers, respectively. Forced expression of RAB25 markedly increased anchorage
      dependent and anchorage-independent cell proliferation, prevented apoptosis and
      anoikis, including that induced by chemotherapy, and increased aggressiveness of
      cancer cells in vivo. The inhibition of apoptosis was associated with a decrease
      in expression of the proapoptotic molecules, BAK and BAX, and activation of the
      antiapoptotic phosphatidylinositol 3 kinase (PI3K) and AKT pathway, providing
      potential mechanisms for the effects of RAB25 on tumor aggressiveness. Overall,
      these studies implicate RAB25, and thus the RAB family of small G proteins, in
      aggressiveness of epithelial cancers.

PMID- 15502843
TI  - Cholinergic agonists inhibit HMGB1 release and improve survival in experimental
      sepsis.
AB  - Physiological anti-inflammatory mechanisms can potentially be exploited for the
      treatment of inflammatory disorders. Here we report that the neurotransmitter
      acetylcholine inhibits HMGB1 release from human macrophages by signaling through
      a nicotinic acetylcholine receptor. Nicotine, a selective cholinergic agonist, is
      more efficient than acetylcholine and inhibits HMGB1 release induced by either
      endotoxin or tumor necrosis factor-alpha (TNF-alpha). Nicotinic stimulation
      prevents activation of the NF-kappaB pathway and inhibits HMGB1 secretion through
      a specific 'nicotinic anti-inflammatory pathway' that requires the alpha7
      nicotinic acetylcholine receptor (alpha7nAChR). In vivo, treatment with nicotine
      attenuates serum HMGB1 levels and improves survival in experimental models of
      sepsis, even when treatment is started after the onset of the disease. These
      results reveal acetylcholine as the first known physiological inhibitor of HMGB1
      release from human macrophages and suggest that selective nicotinic agonists for
      the alpha7nAChR might have therapeutic potential for the treatment of sepsis.

PMID- 15502844
TI  - Aggressive amyloidosis in mice expressing human amyloid peptides with the Arctic
      mutation.
AB  - The Arctic mutation within the amyloid-beta (Abeta) peptide causes Alzheimer
      disease. In vitro, Arctic-mutant Abeta forms (proto)fibrils more effectively than
      wild-type Abeta. We generated transgenic mouse lines expressing Arctic-mutant
      human amyloid precursor proteins (hAPP). Amyloid plaques formed faster and were
      more extensive in Arctic mice than in hAPP mice expressing wild-type Abeta, even
      though Arctic mice had lower Abeta(1-42/1-40) ratios. Thus, the Arctic mutation
      is highly amyloidogenic in vivo.

PMID- 15502845
TI  - Dissecting tumor maintenance requirements using bioluminescence imaging of cell
      proliferation in a mouse glioma model.
AB  - Bioluminescence imaging has previously been used to monitor the formation of
      grafted tumors in vivo and measure cell number during tumor progression and
      response to therapy. The development and optimization of successful cancer
      therapy strategies may well require detailed and specific assessment of
      biological processes in response to mechanistic intervention. Here, we use
      bioluminescence imaging to monitor the cell cycle in a genetically engineered,
      histologically accurate model of glioma in vivo. In these platelet-derived growth
      factor (PDGF)-driven oligodendrogliomas, G1 cell-cycle arrest is generated by
      blockade of either the PDGF receptor or mTOR using small-molecule inhibitors.

PMID- 15502846
TI  - Structural basis for the control of translation initiation during stress.
AB  - During environmental stress, organisms limit protein synthesis by storing
      inactive ribosomes that are rapidly reactivated when conditions improve. Here we
      present structural and biochemical data showing that protein Y, an Escherichia
      coli stress protein, fills the tRNA- and mRNA-binding channel of the small
      ribosomal subunit to stabilize intact ribosomes. Protein Y inhibits translation
      initiation during cold shock but not at normal temperatures. Furthermore, protein
      Y competes with conserved translation initiation factors that, in bacteria, are
      required for ribosomal subunit dissociation. The mechanism used by protein Y to
      reduce translation initiation during stress and quickly release ribosomes for
      renewed translation initiation may therefore occur widely in nature.

PMID- 15502847
TI  - The dynamic response of upstream DNA to transcription-generated torsional stress.
AB  - The torsional stress caused by counter-rotation of the transcription machinery
      and template generates supercoils in a closed topological domain, but has been
      presumed to be too short-lived to be significant in an open domain. This report
      shows that transcribing RNA polymerases dynamically sustain sufficient torsion to
      perturb DNA structure even on linear templates. Assays to capture and measure
      transcriptionally generated torque and to trap short-lived perturbations in DNA
      structure and conformation showed that the transient forces upstream of active
      promoters are large enough to drive the supercoil-sensitive far upstream element
      (FUSE) of the human c-myc into single-stranded DNA. An alternative non-B
      conformation of FUSE found in stably supercoiled DNA is not accessible
      dynamically. These results demonstrate that dynamic disturbance of DNA structure
      provides a real-time measure of ongoing genetic activity.

PMID- 15502848
TI  - Novel roles of TLR3 tyrosine phosphorylation and PI3 kinase in double-stranded
      RNA signaling.
AB  - Double-stranded RNA (dsRNA), a frequent byproduct of virus infection, is
      recognized by Toll-like receptor 3 (TLR3) to mediate innate immune response to
      virus infection. TLR3 signaling activates the transcription factor IRF-3 by its
      Ser/Thr phosphorylation, accompanied by its dimerization and nuclear
      translocation. It has been reported that the Ser/Thr kinase TBK-1 is essential
      for TLR3-mediated activation and phosphorylation of IRF-3. Here we report that
      dsRNA-activated phosphorylation of two specific tyrosine residues of TLR3 is
      essential for initiating two distinct signaling pathways. One involves activation
      of TBK-1 and the other recruits and activates PI3 kinase and the downstream
      kinase, Akt, leading to full phosphorylation and activation of IRF-3. When PI3
      kinase is not recruited to TLR3 or its activity is blocked, IRF-3 is only
      partially phosphorylated and fails to bind the promoter of the target gene in
      dsRNA-treated cells. Thus, the PI3K-Akt pathway plays an essential role in TLR3
      mediated gene induction.

PMID- 15502849
TI  - How and when should we monitor chimerism after allogeneic stem cell
      transplantation?
AB  - SUMMARY: Chimerism analysis has become an important tool for the peri-transplant
      surveillance of engraftment. It offers the possibility to realize impending graft
      rejection and can serve as an indicator for the recurrence of the underlying
      malignant or nonmalignant disease. Most recently, these investigations have
      become the basis for treatment intervention, for example, to avoid graft
      rejection, to maintain engraftment and to treat imminent relapse by pre-emptive
      immunotherapy. This invited review focuses on the clinical implications of
      characterization of hematopoietic chimerism in stem cell transplantation.

PMID- 15502850
TI  - rhG-CSF does not affect the phenotype of adult donor peripheral blood NK cells.
AB  - Considerable evidence in preclinical models as well as in human transplantation
      now suggests that donor-derived natural killer (NK) cells can contribute to
      alloimmune recognition of recipient residual tumour cells. This makes the NK cell
      population an attractive target for in vitro or in vivo manipulations, in order
      to improve the antitumour effect of allogeneic transplantation. However,
      conditions in which allogeneic donor cells are collected vary; several reports
      have emphasised the different phenotypic and functional properties of T cells
      derived from marrow, cord blood or mobilised peripheral blood grafts; others have
      demonstrated different clinical outcomes following blood or marrow
      transplantation after myeloablative conditioning regimens. NK cells have been
      examined in this setting; the availability of new tools to study the expression
      of a variety of surface antigens that are involved in the control of NK cell
      activity offered us an opportunity to extensively characterise the phenotypic
      properties of NK cells from donors, before and after administration of
      pharmacological doses of rhG-CSF used for haematopoietic progenitor mobilisation.
      Our study suggests that rhG-CSF does not reproducibly alter blood NK cell
      phenotype in normal individuals, and thus that donor-derived cells are fully
      equipped to exert their potential antitumour effect.

PMID- 15502851
TI  - Routine screening for psychosocial distress following hematopoietic stem cell
      transplantation.
AB  - The diagnosis and treatment of cancer is often associated with high levels of
      psychosocial distress, yet exploration of these issues is rarely included in
      routine oncologic care. We conducted a pilot study to evaluate the feasibility of
      screening for psychosocial distress after autologous and allogeneic stem cell
      transplantation. A total of 80 adults were enrolled in Boston, MA, USA. Subjects
      completed self-administered assessments prior to hospital admission, at their
      first clinic visit after hospital discharge, and at 100 days post transplant.
      Assessments included validated instruments assessing psychosocial distress and
      quality of life (QOL). Elevated levels of anxiety and/or depression were detected
      in 55% of those providing pre-transplant assessments and were associated with
      compromised QOL. Post transplant screening was successfully performed in 69% of
      subjects and identified that 44% had symptoms of depression, anxiety or post
      traumatic stress disorder. Pre-transplant distress was associated with detection
      of distress after transplantation (81 vs 13%, P< 0.0001). In summary, we detected
      high levels of distress in transplant patients using self-administered tools. Pre
      transplant distress appears to be highly predictive of distress post transplant
      and is a feasible marker to target screening and intervention programs.

PMID- 15502852
TI  - Severe metabolic abnormalities after allogeneic hematopoietic cell
      transplantation.
AB  - Severe metabolic abnormalities occurring within 100 days after allogeneic
      hematopoietic cell transplantation (HCT) were investigated in 311 patients. The
      metabolic abnormalities included hyper- and hypocalcemia, hypophosphatemia, hyper
      and hypokalemia, hyper- and hyponatremia, hyper- and hypomagnesemia,
      hypercholesterolemia, hyper- and hypoglycemia, and hyperuricemia. Severe
      abnormalities, defined as grades III-V by NCI CTCAE v3.0, occurred in 269
      patients (86.5%). Multivariate analysis revealed that patients with moderate-to
      severe hepatic veno-occlusive disease had significantly higher risk for the
      occurrence of severe metabolic abnormalities. Grades III-IV acute graft-versus
      host disease was the most frequently associated with individual metabolic
      abnormalities. Patients with at least one severe metabolic abnormality had
      significantly higher day 100 nonrelapse mortality (P=0.015) and lower 5-year
      overall survival (P=0.002) than those without severe abnormalities. The number of
      metabolic abnormalities also stratified the patients with different clinical
      outcomes. In conclusion, severe metabolic abnormalities occurring within 100 days
      after allogeneic HCT were common, and their occurrence was significantly
      associated with inferior clinical outcomes. These results indicate that metabolic
      parameters should be monitored in patients undergoing allogeneic HCT and that the
      occurrence of severe metabolic abnormalities should be considered an important
      toxicity parameter in prospective clinical trials regarding allogeneic HCT.

PMID- 15502853
TI  - Intravenous busulfan in children prior to stem cell transplantation: study of
      pharmacokinetics in association with early clinical outcome and toxicity.
AB  - We studied the pharmacokinetics of intravenous busulfan (Bu) in children in order
      to further optimize intravenous Bu dosing in relation to toxicity and survival. A
      total of 31 children undergoing Bu-based conditioning for allogeneic SCT were
      enrolled in a study. The starting dose was 1.0 mg/kg (age < 4 years) and 0.8
      mg/kg (age > or =4 years), four doses per day during 4 days. Dose adjustment was
      allowed up to a maximum dose of 1.0 mg/kg per dose if the target area under the
      serum concentration-time curve (AUC) was not reached. Pharmacokinetic studies
      were performed after the first dose. Donor engraftment was established in 28 out
      of 31 patients. The average AUC after the first dose was the same in children < 4
      years as in children > or =4 years. Mean clearance was higher in children < 4
      years than in children > or =4 years. In 35% of all patients, total AUC was
      within the target AUC. The other children's AUCs were below the target range. No
      relationships were found between systemic exposure to Bu and toxicity or clinical
      outcome. We concluded that, in accordance with previous data, within the observed
      AUCs no clear relationship was observed between Bu AUC and outcome with respect
      to toxicity, engraftment and relapse.

PMID- 15502854
TI  - Nonhematologic malignancies after allogeneic hematopoietic stem cell
      transplantation: incidence and molecular monitoring.
AB  - Survivors of allogeneic hematopoietic stem cell transplantation (HSCT) are at a
      life-long increased risk of secondary nonhematologic malignancies. In 615 adult
      Chinese allogeneic HSCT patients, nine developed nonhematologic malignancies. The
      5-year cumulative incidence was 6.1%, 4.5 times the background cancer incidence.
      Early-onset (within first 6 months) and late-onset (>3 years) subtypes were
      observed. Secondary cancers included hepatocellular carcinoma, oral and
      esophageal squamous cell tumors and lung adenocarcinoma in a female nonsmoker.
      The spectrum reflected local cancer epidemiology, which was different from
      Western populations. The pathogenesis might be related to acceleration of pre
      existing cancers (early-onset type), or prolonged immunosuppression (late-onset
      type). DNA chimerism studies showed that all tumors were recipient-derived. In
      the plasma, DNA in all cases was apparently donor-derived, although aberrantly
      methylated p15 was detectable in a patient with a p15-methylated secondary
      cancer, implying that minute quantities of tumor (and therefore recipient)
      derived DNA might be present.

PMID- 15502855
TI  - G-CSF-mobilised granulocyte transfusion to an ALL patient complicated by
      cytomegalovirus transmission.

PMID- 15502856
TI  - Real-time quantitative RT-PCR identifies distinct c-RET, RET/PTC1 and RET/PTC3
      expression patterns in papillary thyroid carcinoma.
AB  - RET/PTC1 and RET/PTC3 are the markers for papillary thyroid carcinoma. Their
      reported prevalence varies broadly. Nonrearranged c-RET has also been detected in
      a variable proportion of papillary carcinomas. The published data suggest that a
      wide range in expression levels may contribute to the different frequency of c
      RET and, particularly, of RET/PTC detection. However, quantitative expression
      analysis has never been systematically carried out. We have analyzed by real-time
      RT-PCR 25 papillary carcinoma and 12 normal thyroid samples for RET/PTC1,
      RET/PTC3 and for RET exons 10-11 and 12-13, which are adjacent to the
      rearrangement site. The variability in mRNA levels was marked and four carcinoma
      groups were identified: one lacking RET/PTC rearrangement with balanced RET exon
      levels similar to those of the normal samples (7/25 cases, 28%), the second (6/25
      cases, 24%) with balanced RET expression and very low levels of RET/PTC1, the
      third with unbalanced RET exons 10-11 and 12-13 expression, high RET/PTC1 levels
      but no RET/PTC3 (7/25 cases, 28%), and the fourth with unbalanced RET expression,
      high RET/PTC1 levels and low levels of RET/PTC3 (5/25 cases, 20%). Papillary
      carcinomas with high RET/PTC1 expression showed an association trend for large
      tumor size (P=0.063). Our results indicate that the variability in c-RET and
      RET/PTC mRNA levels contributes to the apparent inconsistencies in their reported
      detection rates and should be taken into account not only for diagnostic purposes
      but also to better understand the role of c-RET activation in thyroid
      tumorigenesis.

PMID- 15502857
TI  - Hh pathway expression in human gut tissues and in inflammatory gut diseases.
AB  - Sonic hedgehog (Shh) directs early gut patterning via epithelial-mesenchymal
      signaling and remains expressed in endoderm-derived tissues into the adult
      period. In human adult gut epithelium SHH/SHH expression is strongest in basal
      layers, which suggests that SHH may function in the maintenance of gut epithelial
      stem or progenitor cells. Recent publications suggest a role for aberrant SHH/SHH
      expression in gut epithelial neoplasias. We hypothesized that the regenerating
      gut epithelium in inflammatory gut disorders would show an upregulation of
      SHH/SHH signaling and this abnormal signal may explain the increased incidence of
      neoplasia in these diseases. Archived healthy gut and inflammatory gut diseased
      tissues were analyzed by RNA in situ hybridization and immunohistochemistry to
      describe location and levels of SHH signaling. We show that SHH/SHH and its
      receptor PTCH1/PTCH1 expression is restricted to the glandular epithelium of the
      gut, in an antiluminal pattern (strongest in basal layers and weak to absent in
      luminal epithelium). Inflammatory diseases of the gut show dramatic increases in
      epithelial SHH signaling. Expression increases in inflamed glandular epithelium
      (including metaplastic glandular epithelium), losing its radial (crypt-villous)
      polarity, and expression appears upregulated and present in all epithelial cells.
      We also describe strong SHH/SHH and PTCH1/PTCH1 expression in intraepithelial and
      mucosal inflammatory cells. We suggest that SHH signaling in inflammatory
      diseases of the gut acts to ensure stem cell restitution of damaged mucosal
      epithelium. However, such signaling may also present a risk for neoplastic
      transformation.

PMID- 15502859
TI  - Liver biopsies from human females contain male hepatocytes in the absence of
      transplantation.
AB  - Fetal cells derived from pregnancy can persist in a woman's blood and tissues for
      decades and have been implicated in the pathogenesis of autoimmune disease.
      Transplantation studies based on donor sex mismatch suggest that circulating stem
      cells can lead to liver regeneration with donor-derived hepatocytes. However,
      male cells in female liver could derive from pregnancy. We investigated male
      cells in liver biopsies from women with sons and asked whether they were
      hematopoietic cells or hepatocytes. Fluorescence in situ hybridization for X- and
      Y-chromosomes with concomitant immunohistochemistry was employed to study 28
      female liver biopsies: 14 with the autoimmune disease primary biliary cirrhosis
      (PBC), eight with Hepatitis C, and six with other diseases. Total male cells and
      those expressing hematopoietic (CD45) or hepatocyte (CAM-5.2) markers were
      quantified. None of the male cells were hematopoietic in origin, as shown by lack
      of CD45 expression. Instead, male cells with hepatocyte morphology expressing the
      hepatocyte marker CAM 5.2 were found in 25% of all biopsies (36% of PBC and 14%
      of others). Overall, male cells were found in 36% of female liver biopsies. Of
      the PBC livers 43% had male cells compared to 25% of Hepatitis C biopsies and 33%
      of others. There was a trend toward increased numbers of male cells in PBC
      compared to others (mean 1 per 30,000 host cells vs 0.17 in Hepatitis C and 0.35
      in others). Thus, male cells found in livers of women with sons include cells
      that express hepatocyte antigens. Therefore, transplantation and stem cell
      differentiation studies using sex difference to conclude that donor cells
      regenerate liver may be confounded by fetal microchimerism. Whether fetal cells
      play a role in autoimmune diseases like PBC merits further investigation.

PMID- 15502858
TI  - Lack of significant skin inflammation during elimination by apoptosis of large
      numbers of mouse cutaneous mast cells after cessation of treatment with stem cell
      factor.
AB  - We previously reported that subcutaneous (s.c.) administration of stem cell
      factor (SCF), the ligand for the c-Kit receptor, to the back skin of mice
      promotes marked local increases in the numbers of cutaneous mast cells (MCs), and
      that cessation of SCF treatment results in the rapid reduction of cutaneous MC
      populations by apoptosis. In the present study, we used the 125I-fibrin
      deposition assay, a very sensitive method for quantifying increased vascular
      permeability, to assess whether the clearance of large numbers of apoptotic MCs
      is associated with significant cutaneous inflammation. The s.c. injection of
      rrSCF164 (30 or 100 microg/kg/day) or rrSCF164-peg (polyethylene glycol-treated
      SCF, 30 or 100 microg/kg/day) for 23 days increased the numbers of dermal MCs at
      skin injection sites from 5.1+/-0.7 MCs/mm2 to 36.4+/-4.1, 34.7+/-9.7, 52.5+/
      5.8, and 545+/-97 MCs/mm2, respectively. In contrast, MC numbers were markedly
      lower in mice that had been treated with SCF for 21 days, followed by 2 days of
      injection with the vehicle alone. Notably, when tested during the period of rapid
      reduction of skin MCs,125I-fibrin deposition in the skin was very similar to that
      in mice receiving continuous treatment with SCF or vehicle. We conclude that the
      rapid elimination of even very large populations of MCs by apoptosis, which also
      results in the clearance of the considerable quantities of proinflammatory
      products stored by these cells, does not lead to significant local cutaneous
      inflammatory responses.

PMID- 15502860
TI  - Inhibition of transforming growth factor beta decreases pancreatic fibrosis and
      protects the pancreas against chronic injury in mice.
AB  - Transforming growth factor-beta (TGF-beta) is an important cytokine in the
      fibrogenesis in many organs, including the pancreas. Using an adenoviral vector
      expressing the entire extracellular domain of type II human TGF-beta receptor
      (AdTbeta-ExR), we investigated whether inhibition of TGF-beta action is effective
      against persistent pancreatic fibrosis, and whether it exerts a beneficial effect
      on the pancreas in the process of chronic injury. To induce chronic pancreatic
      injury and pancreatic fibrosis, mice were subjected to three episodes of acute
      pancreatitis induced by six intraperitoneal injections of 50 microg/kg body
      weight cerulein at hourly intervals, per week for 3 consecutive weeks. Mice were
      infected once with AdTbeta-ExR, or with a control adenoviral vector expressing
      bacterial beta-galactosidase (AdLacZ). Pancreatic fibrosis was evaluated by
      histology and hydroxyproline content. Activation of pancreatic stellate cells
      (PSCs) was assessed by immunostaining for alpha-smooth muscle actin. Apoptosis
      and proliferation of acinar cells were assessed by immunostaining of ssDNA and Ki
      67, respectively. Three-week cerulein injection induced pancreatic fibrosis and
      pancreatic atrophy with proliferation of activated PSCs. In AdTbeta-ExR-injected
      mice, but not AdLacZ-injected mice, pancreatic fibrosis was significantly
      attenuated. This finding was accompanied by a reduction of activated PSCs.
      AdTbeta-ExR, but not AdLacZ, significantly increased pancreas weight after
      chronic pancreatic injury. AdTbeta-ExR did not change the proportion of
      proliferating acinar cells, whereas it reduced the number of apoptotic acinar
      cells. Our results demonstrate that inhibition of TGF-beta action not only
      decreases pancreatic fibrosis but also protects the pancreas against chronic
      injury by preventing acinar cell apoptosis.

PMID- 15502861
TI  - Angiogenic endothelium-specific nestin expression is enhanced by the first intron
      of the nestin gene.
AB  - Nestin is a member of intermediate filaments abundantly expressed in neural stem
      cells and glioblastomas. The nestin gene has four exons and three introns, and
      neural cell-specific expression is regulated by the second intron. We previously
      reported that nestin was invariably detected in the tumor endothelium in gliomas
      even though tumor cells were negative for nestin. In the present study, we
      further confirmed nestin immunostaining in tumor endothelium of a variety of
      common cancers, including lung, stomach, colon, and cervical carcinomas. We
      examined an endothelium-specific regulator using human umbilical vein endothelial
      cells (HUVECs) and human glioblastoma-derived U251 cells. In a luciferase
      reporter assay, the first intron plus 5' upstream promoter (5'UP) gave the
      highest activity, followed by 5'UP, and the second intron plus 5'UP. However, the
      assay values were much lower by HUVEC extracts than by U251 cell extracts.
      Although green fluorescent protein expression was positive over all U251 cells
      under either the first intron, second intron, or ubiquitously active CAG
      promoter, the fluorescence in HUVECs was limited to a few cells even under the
      first intron. This difference came from the growth feature of HUVECs which
      exhibit growth arrest by contact inhibition. We found that the nestin expression
      was specific to proliferative endothelium, by using proliferation markers in
      hemangioblastomas and in situ hybridization. Using an endothelial tube formation
      assay, tyrosine kinase domain-deleted VEGF receptor KDR effectively abolished the
      tube formation under the first intron. We suggest that the nestin expression in
      tumor endothelium is enhanced by the first intron.

PMID- 15502862
TI  - Colorectal cancers in a new mouse model of familial adenomatous polyposis:
      influence of genetic and environmental modifiers.
AB  - Murine models of familial adenomatous polyposis harbor a germinal heterozygous
      mutation on Apc tumor suppressor gene. They are valuable tools for studying
      intestinal carcinogenesis, as most human sporadic cancers contain inactivating
      mutations of APC. However, Apc(+/-) mice, such as the well-characterized
      Apc(Min/+) model, develop cancers principally in the small intestine, while
      humans develop mainly colorectal cancers. We used a Cre-loxP strategy to achieve
      a new model of germline Apc invalidation in which exon 14 is deleted. We compared
      the phenotype of these Apc(Delta14/+) mice to that of the classical Apc(Min/+).
      The main phenotypic difference is the shift of the tumors in the distal colon and
      rectum, often associated with a rectal prolapse. Thus, the severity of the
      colorectal phenotype is partly due to the particular mutation Delta14, but also
      to environmental parameters, as mice raised in conventional conditions developed
      more colon cancers than those raised in pathogen-free conditions. All lesions,
      including early lesions, revealed Apc LOH and loss of Apc gene expression. They
      accumulated beta-catenin, overexpressed the beta-catenin target genes cyclin D1
      and c-Myc, and the distribution pattern of glutamine synthetase, a beta-catenin
      target gene recently identified in the liver, was mosaic in intestinal adenomas.
      The Apc(Delta14/+) model is thus a useful new tool for studies on the molecular
      mechanisms of colorectal tumorigenesis.

PMID- 15502868
TI  - Sensitivity to oxidative stress in DJ-1-deficient dopamine neurons: an ES-
      derived cell model of primary Parkinsonism.
AB  - The hallmark of Parkinson's disease (PD) is the selective loss of dopamine
      neurons in the ventral midbrain. Although the cause of neurodegeneration in PD is
      unknown, a Mendelian inheritance pattern is observed in rare cases, indicating a
      genetic factor. Furthermore, pathological analyses of PD substantia nigra have
      correlated cellular oxidative stress and altered proteasomal function with PD.
      Homozygous mutations in DJ-1 were recently described in two families with
      autosomal recessive Parkinsonism, one of which is a large deletion that is likely
      to lead to loss of function. Here we show that embryonic stem cells deficient in
      DJ-1 display increased sensitivity to oxidative stress and proteasomal
      inhibition. The accumulation of reactive oxygen species in toxin-treated DJ-1
      deficient cells initially appears normal, but these cells are unable to cope with
      the consequent damage that ultimately leads to apoptotic death. Furthermore, we
      find that dopamine neurons derived from in vitro-differentiated DJ-1-deficient
      embryonic stem cells display decreased survival and increased sensitivity to
      oxidative stress. These data are consistent with a protective role for DJ-1, and
      demonstrate the utility of genetically modified embryonic stem cell-derived
      neurons as cellular models of neuronal disorders.

PMID- 15502869
TI  - Protein thiol modifications visualized in vivo.
AB  - Thiol-disulfide interconversions play a crucial role in the chemistry of
      biological systems. They participate in the major systems that control the
      cellular redox potential and prevent oxidative damage. In addition, thiol
      disulfide exchange reactions serve as molecular switches in a growing number of
      redox-regulated proteins. We developed a differential thiol-trapping technique
      combined with two-dimensional gel analysis, which in combination with genetic
      studies, allowed us to obtain a snapshot of the in vivo thiol status of cellular
      proteins. We determined the redox potential of protein thiols in vivo, identified
      and dissected the in vivo substrate proteins of the major cellular thiol
      disulfide oxidoreductases, and discovered proteins that undergo thiol
      modifications during oxidative stress. Under normal growth conditions most
      cytosolic proteins had reduced cysteines, confirming existing dogmas. Among the
      few partly oxidized cytosolic proteins that we detected were proteins that are
      known to form disulfide bond intermediates transiently during their catalytic
      cycle (e.g., dihydrolipoyl transacetylase and lipoamide dehydrogenase). Most
      proteins with highly oxidized thiols were periplasmic proteins and were found to
      be in vivo substrates of the disulfide-bond-forming protein DsbA. We discovered a
      substantial number of redox-sensitive cytoplasmic proteins, whose thiol groups
      were significantly oxidized in strains lacking thioredoxin A. These included
      detoxifying enzymes as well as many metabolic enzymes with active-site cysteines
      that were not known to be substrates for thioredoxin. H(2)O(2)-induced oxidative
      stress resulted in the specific oxidation of thiols of proteins involved in
      detoxification of H(2)O(2) and of enzymes of cofactor and amino acid biosynthesis
      pathways such as thiolperoxidase, GTP-cyclohydrolase I, and the cobalamin
      independent methionine synthase MetE. Remarkably, a number of these proteins were
      previously or are now shown to be redox regulated.

PMID- 15502870
TI  - Oxidative stress inactivates cobalamin-independent methionine synthase (MetE) in
      Escherichia coli.
AB  - In nature, Escherichia coli are exposed to harsh and non-ideal growth
      environments-nutrients may be limiting, and cells are often challenged by
      oxidative stress. For E. coli cells confronting these realities, there appears to
      be a link between oxidative stress, methionine availability, and the enzyme that
      catalyzes the final step of methionine biosynthesis, cobalamin-independent
      methionine synthase (MetE). We found that E. coli cells subjected to transient
      oxidative stress during growth in minimal medium develop a methionine auxotrophy,
      which can be traced to an effect on MetE. Further experiments demonstrated that
      the purified enzyme is inactivated by oxidized glutathione (GSSG) at a rate that
      correlates with protein oxidation. The unique site of oxidation was identified by
      selectively cleaving N-terminally to each reduced cysteine and analyzing the
      results by liquid chromatography mass spectrometry. Stoichiometric
      glutathionylation of MetE by GSSG occurs at cysteine 645, which is strategically
      located at the entrance to the active site. Direct evidence of MetE oxidation in
      vivo was obtained from thiol-trapping experiments in two different E. coli
      strains that contain highly oxidizing cytoplasmic environments. Moreover, MetE is
      completely oxidized in wild-type E. coli treated with the thiol-oxidizing agent
      diamide; reduced enzyme reappears just prior to the cells resuming normal growth.
      We argue that for E. coli experiencing oxidizing conditions in minimal medium,
      MetE is readily inactivated, resulting in cellular methionine limitation.
      Glutathionylation of the protein provides a strategy to modulate in vivo activity
      of the enzyme while protecting the active site from further damage, in an easily
      reversible manner. While glutathionylation of proteins is a fairly common mode of
      redox regulation in eukaryotes, very few proteins in E. coli are known to be
      modified in this manner. Our results are complementary to the independent
      findings of Leichert and Jakob presented in the accompanying paper (Leichert and
      Jakob 2004), which provide evidence that MetE is one of the proteins in E. coli
      most susceptible to oxidation. In eukaryotes, glutathionylation of key proteins
      involved in protein synthesis leads to inhibition of translation. Our studies
      suggest a simpler mechanism is employed by E. coli to achieve the same effect.

PMID- 15502871
TI  - Genetic analysis of lice supports direct contact between modern and archaic
      humans.
AB  - Parasites can be used as unique markers to investigate host evolutionary history,
      independent of host data. Here we show that modern human head lice, Pediculus
      humanus, are composed of two ancient lineages, whose origin predates modern Homo
      sapiens by an order of magnitude (ca. 1.18 million years). One of the two louse
      lineages has a worldwide distribution and appears to have undergone a population
      bottleneck ca. 100,000 years ago along with its modern H. sapiens host.
      Phylogenetic and population genetic data suggest that the other lineage, found
      only in the New World, has remained isolated from the worldwide lineage for the
      last 1.18 million years. The ancient divergence between these two lice is
      contemporaneous with splits among early species of Homo, and cospeciation
      analyses suggest that the two louse lineages codiverged with a now extinct
      species of Homo and the lineage leading to modern H. sapiens. If these lice
      indeed codiverged with their hosts ca. 1.18 million years ago, then a recent host
      switch from an archaic species of Homo to modern H. sapiens is required to
      explain the occurrence of both lineages on modern H. sapiens. Such a host switch
      would require direct physical contact between modern and archaic forms of Homo.

PMID- 15502872
TI  - X chromosome sites autonomously recruit the dosage compensation complex in
      Drosophila males.
AB  - It has been proposed that dosage compensation in Drosophila males occurs by
      binding of two core proteins, MSL-1 and MSL-2, to a set of 35-40 X chromosome
      "entry sites" that serve to nucleate mature complexes, termed compensasomes,
      which then spread to neighboring sequences to double expression of most X-linked
      genes. Here we show that any piece of the X chromosome with which compensasomes
      are associated in wild-type displays a normal pattern of compensasome binding
      when inserted into an autosome, independently of the presence of an entry site.
      Furthermore, in chromosomal rearrangements in which a piece of X chromosome is
      inserted into an autosome, or a piece of autosome is translocated to the X
      chromosome, we do not observe spreading of compensasomes to regions of autosomes
      that have been juxtaposed to X chromosomal material. Taken together these results
      suggest that spreading is not involved in dosage compensation and that nothing
      distinguishes an entry site from the other X chromosome sites occupied by
      compensasomes beyond their relative affinities for compensasomes. We propose a
      new model in which the distribution of compensasomes along the X chromosome is
      achieved according to the hierarchical affinities of individual binding sites.

PMID- 15502873
TI  - Endemic infection of the amphibian chytrid fungus in a frog community post
      decline.
AB  - The chytrid fungus Batrachochytrium dendrobatidis has been implicated in the
      decline and extinction of numerous frog species worldwide. In Queensland,
      Australia, it has been proposed as the cause of the decline or apparent
      extinction of at least 14 high-elevation rainforest frog species. One of these,
      Taudactylus eungellensis, disappeared from rainforest streams in Eungella
      National Park in 1985-1986, but a few remnant populations were subsequently
      discovered. Here, we report the analysis of B. dendrobatidis infections in toe
      tips of T. eungellensis and sympatric species collected in a mark-recapture study
      between 1994 and 1998. This longitudinal study of the fungus in individually
      marked frogs sheds new light on the effect of this threatening infectious process
      in field, as distinct from laboratory, conditions. We found a seasonal peak of
      infection in the cooler months, with no evidence of interannual variation. The
      overall prevalence of infection was 18% in T. eungellensis and 28% in Litoria
      wilcoxii/jungguy, a sympatric frog that appeared not to decline in 1985-1986. No
      infection was found in any of the other sympatric species. Most importantly, we
      found no consistent evidence of lower survival in T. eungellensis that were
      infected at the time of first capture, compared with uninfected individuals.
      These results refute the hypothesis that remnant populations of T. eungellensis
      recovered after a B. dendrobatidis epidemic because the pathogen had disappeared.
      They show that populations of T. eungellensis now persist with stable, endemic
      infections of B. dendrobatidis.

PMID- 15502874
TI  - DJ-1 is a redox-dependent molecular chaperone that inhibits alpha-synuclein
      aggregate formation.
AB  - Parkinson's disease (PD) pathology is characterized by the degeneration of
      midbrain dopamine neurons (DNs) ultimately leading to a progressive movement
      disorder in patients. The etiology of DN loss in sporadic PD is unknown, although
      it is hypothesized that aberrant protein aggregation and cellular oxidative
      stress may promote DN degeneration. Homozygous mutations in DJ-1 were recently
      described in two families with autosomal recessive inherited PD (Bonifati et al.
      2003). In a companion article (Martinat et al. 2004), we show that mutations in
      DJ-1 alter the cellular response to oxidative stress and proteasomal inhibition.
      Here we show that DJ-1 functions as a redox-sensitive molecular chaperone that is
      activated in an oxidative cytoplasmic environment. We further demonstrate that DJ
      1 chaperone activity in vivo extends to alpha-synuclein, a protein implicated in
      PD pathogenesis.

PMID- 15502876
TI  - A hard way to the nucleus.
AB  - As a member of the Retrovirus family, human immunodeficiency virus (HIV), a
      causative agent of AIDS, replicates by integrating its genome into the host
      cell's nuclear DNA. However, in contrast to most retroviruses that depend on
      mitotic dissolution of the nuclear envelope to gain access to the host cell's
      genome, the HIV pre-integration complex can enter the nucleus of the target cell
      during the interphase. Such capacity greatly enhances HIV replication and allows
      the virus to productively infect terminally differentiated nonproliferating
      cells, such as macrophages. Infection of macrophages is a critical factor in the
      pathogenesis of diseases caused by HIV-1 and other lentiviruses. The mechanisms
      responsible for this unusual feature of HIV have enticed researchers since the
      early 90s, when the first characterization of the HIV-1 pre-integration complex
      was reported. Several viral factors, including matrix protein, integrase, viral
      protein R, and central DNA flap, have been proposed as regulators of HIV-1
      nuclear import, only to be later shown as nonessential for this process. As a
      result, after more than a decade of intense research, there is still no consensus
      on which HIV-1 and cellular proteins control this critical step in HIV-1
      replication. In this review, we will discuss recent advances and suggest possible
      solutions to the controversial issue of HIV-1 nuclear import.

PMID- 15502877
TI  - Tissue factor and cancer metastasis: the role of intracellular and extracellular
      signaling pathways.
AB  - Tissue factor (TF) initiates the coagulation cascade but also plays a role in
      cancer and metastasis. This transmembrane protein is frequently upregulated on
      tumor cells and cells that show metastatic behavior. Furthermore, it is a
      significant risk factor for hepatic metastasis in patients suffering from colon
      cancer. Recently, it has been shown that TF, together with its natural ligand
      factor VIIa, induces intracellular changes, such as signal transduction cascades,
      gene transcription, and protein synthesis. Moreover, TF:factor VIIa interaction
      leads to survival of cells that have been stimulated to undergo apoptosis.
      Together with TF-dependent processes such as angiogenesis, these intracellular
      phenomena form a plausible explanation for the influence of TF on metastasis. In
      this review, we will discuss these phenomena in more detail and hypothesize on
      their role in TF-driven metastasis.

PMID- 15502875
TI  - Human MicroRNA targets.
AB  - MicroRNAs (miRNAs) interact with target mRNAs at specific sites to induce
      cleavage of the message or inhibit translation. The specific function of most
      mammalian miRNAs is unknown. We have predicted target sites on the 3'
      untranslated regions of human gene transcripts for all currently known 218
      mammalian miRNAs to facilitate focused experiments. We report about 2,000 human
      genes with miRNA target sites conserved in mammals and about 250 human genes
      conserved as targets between mammals and fish. The prediction algorithm optimizes
      sequence complementarity using position-specific rules and relies on strict
      requirements of interspecies conservation. Experimental support for the validity
      of the method comes from known targets and from strong enrichment of predicted
      targets in mRNAs associated with the fragile X mental retardation protein in
      mammals. This is consistent with the hypothesis that miRNAs act as sequence
      specific adaptors in the interaction of ribonuclear particles with
      translationally regulated messages. Overrepresented groups of targets include
      mRNAs coding for transcription factors, components of the miRNA machinery, and
      other proteins involved in translational regulation, as well as components of the
      ubiquitin machinery, representing novel feedback loops in gene regulation.
      Detailed information about target genes, target processes, and open-source
      software for target prediction (miRanda) is available at http://www.microrna.org.
      Our analysis suggests that miRNA genes, which are about 1% of all human genes,
      regulate protein production for 10% or more of all human genes.

PMID- 15502878
TI  - Deficiency of neuropilin 2 suppresses VEGF-induced retinal neovascularization.
AB  - Vascular endothelial growth factor (VEGF) plays a central role in the development
      of ocular neovascularization (NV) and is an excellent target for therapeutic
      intervention. VEGF acts through several receptors, including VEGF receptor 1,
      VEGF receptor 2, neuropilin-1 (Npn1), and Npn2, but the exact role of these
      receptors in the development of retinal NV is unknown. In this study, we
      investigated the expression of npn2 mRNA during new blood vessel growth in the
      retina and used npn2 knockout mice to assess the impact of deficiency of Npn2 on
      retinal NV. The level of npn2 mRNA in the retina increased during retinal
      vascular development, after exposure to hyperoxia, and after the onset of retinal
      ischemia. Immunohistochemistry showed colocalization of Npn2 with a vascular
      marker in retinal NV. Compared with littermate controls, mice deficient in Npn2
      had significantly less ischemia-induced retinal NV and very little subretinal NV
      due to expression of a Vegf transgene. These data suggest that Npn2 facilitates
      VEGF-induced retinal NV and may constitute a useful target for therapeutic
      intervention in ocular diseases complicated by NV.

PMID- 15502879
TI  - Gene expression profile in interleukin-4-stimulated human vascular endothelial
      cells.
AB  - Interleukin-4 (IL-4)-mediated pro-oxidative and pro-inflammatory vascular
      environments have been implicated in the pathogenesis of atherosclerosis. The
      cellular and molecular regulatory mechanisms underlying this process, however,
      are not fully understood. In the present study, we employed GeneChip microarray
      analysis to investigate global gene expression patterns in human vascular
      endothelial cells after treatment with IL-4. Our results showed that mRNA levels
      of a total of 106 genes were significantly up-regulated and 41 genes
      significantly down-regulated with more than a 2-fold change. The majority of
      these genes are critically involved in the regulation of inflammatory responses,
      apoptosis, signal transduction, transcription factors, and metabolism; functions
      of the remaining genes are unknown. The changes in gene expression of selected
      genes related to inflammatory reactions, such as vascular cell adhesion molecule
      1 (VCAM-1), E-selectin, monocyte chemoattractant protein-1 (MCP-1), and
      interleukin-6 (IL-6), were verified by quantitative real-time reverse
      transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent
      assay (ELISA) analyses. IL-4 treatment also significantly increased the adherence
      of inflammatory cells to endothelial cell monolayers in a dose-dependent manner.
      These results may help determine the molecular mechanisms of action of IL-4 in
      human vascular endothelium. In addition, a better understanding of IL-4-induced
      vascular injury at the level of gene expression could lead to the identification
      of new therapeutic strategies for atherosclerosis.

PMID- 15502880
TI  - Angiotensin II-mediated endothelial dysfunction: role of poly(ADP-ribose)
      polymerase activation.
AB  - Angiotensin II (AII) contributes to the pathogenesis of many cardiovascular
      disorders. Oxidant-mediated activation of poly(adenosine diphosphate-ribose)
      polymerase (PARP) plays a role in the development of endothelial dysfunction and
      the pathogenesis of various cardiovascular diseases. We have investigated whether
      activation of the nuclear enzyme PARP contributes to the development of AII
      induced endothelial dysfunction. AII in cultured endothelial cells induced DNA
      single-strand breakage and dose-dependently activated PARP, which was inhibited
      by the AII subtype 1 receptor antagonist, losartan; the nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidase inhibitor, apocynin; and the nitric oxide
      synthase inhibitor, N-nitro-L-arginine methyl ester. Infusion of sub-pressor
      doses of AII to rats for 7 to 14 d induced the development of endothelial
      dysfunction ex vivo. The PARP inhibitors PJ34 or INO-1001 prevented the
      development of the endothelial dysfunction and restored normal endothelial
      function. Similarly, PARP-deficient mice infused with AII for 7 d were found
      resistant to the AII-induced development of endothelial dysfunction, as opposed
      to the wild-type controls. In spontaneously hypertensive rats there was marked
      PARP activation in the aorta, heart, and kidney. The endothelial dysfunction, the
      cardiovascular alterations and the activation of PARP were prevented by the
      angiotensin-converting enzyme inhibitor enalapril. We conclude that AII, via AII
      receptor subtype 1 activation and reactive oxygen and nitrogen species
      generation, triggers DNA breakage, which activates PARP in the vascular
      endothelium, leading to the development of endothelial dysfunction in
      hypertension.

PMID- 15502881
TI  - Attenuated hippocampus-dependent learning and memory decline in transgenic
      TgAPPswe Fischer-344 rats.
AB  - Alzheimer's disease (AD) is characterized by increased beta amyloid (Abeta)
      levels, extracellular Abeta deposits in senile plaques, neurofibrillary tangles,
      and neuronal loss. However, the physiological role of normal levels of Abeta and
      its parent protein, the amyloid precursor protein (APP) are unknown. Here we
      report that low-level transgenic (Tg) expression of the Swedish APP mutant gene
      (APPswe) in Fischer-344 rats results in attenuated age-dependent cognitive
      performance decline in 2 hippocampus-dependent learning and memory tasks compared
      with age-matched nontransgenic Fischer-344 controls. TgAPPswe rats exhibit mild
      increases in brain APP mRNA (56.8%), Abeta-42 (21%), and Abeta-40 (6.1%) peptide
      levels at 12 mo of age, with no extracellular Abeta deposits or senile plaques at
      6, 12, and 18 mo of age, whereas 3- to 6-fold increases in Abeta levels are
      detected in plaque-positive human AD patients and transgenic mouse models. The
      data support the hypothesis that a threshold paradigm underlies Abeta-related
      pathology, below which APP expression may play a physiological role in specific
      hippocampus-dependent tasks, most likely related to its neurotrophic role.

PMID- 15502882
TI  - Reduced peripheral PGE2 biosynthesis in Plasmodium falciparum malaria occurs
      through hemozoin-induced suppression of blood mononuclear cell cyclooxygenase-2
      gene expression via an interleukin-10-independent mechanism.
AB  - Molecular immunologic determinants of disease severity during Plasmodium
      falciparum malaria are largely undetermined. Our recent investigations showed
      that peripheral blood mononuclear cell (PBMC) cyclooxygenase-2 (COX-2) gene
      expression and plasma prostaglandin E(2) (PGE(2)) production are suppressed in
      children with falciparum malaria relative to healthy, malaria-exposed children
      with partial immunity. Furthermore, decreased COX-2/PGE(2) levels were
      significantly associated with increased plasma interleukin-10 (IL-10), an anti
      inflammatory cytokine that inhibits the expression of COX-2 gene products. To
      determine the mechanism(s) responsible for COX-2-derived PGE(2) suppression,
      PBMCs were cultured from children with falciparum malaria. PGE(2) production was
      suppressed under baseline and COX-2-promoting conditions (stimulation with
      lipopolysaccharide [LPS] and interferon [IFN]-gamma) over prolonged periods,
      suggesting that an in vivo-derived product(s) was responsible for reduced PGE(2)
      biosynthesis. Ingestion of hemozoin (malarial pigment) by PBMC was investigated
      as a source of COX-2/PGE(2) suppression in PBMCs from healthy, malaria-naive
      adults. In addition, synthetically prepared hemozoin, beta-hematin, was used to
      investigate the effects of the core iron component of hemozoin,
      ferriprotoporphyrin-IX (FPIX). Physiologic concentrations of hemozoin or b
      hematin suppressed LPS- and IFN-gamma-induced COX-2 mRNA in a time- and dose
      dependent manner, resulting in decreased COX-2 protein and PGE(2) production.
      Suppression of COX-2/PGE(2) by hemozoin was not due to decreased cell viability
      as evidenced by examination of mitochondrial bioactivity. These data illustrate
      that ingestion of FPIX by blood mononuclear cells is responsible for suppression
      of COX-2/PGE(2). Although hemozoin induced overproduction of IL-10, neutralizing
      IL-10 antibodies failed to restore PGE(2) production. Thus, acquisition of
      hemozoin by blood mononuclear cells is responsible for suppression of PGE(2) in
      malaria through inhibition of de novo COX-2 transcripts via molecular mechanisms
      independent of increased IL-10 production.

PMID- 15502883
TI  - Epigallocatechin, a green tea polyphenol, attenuates myocardial ischemia
      reperfusion injury in rats.
AB  - Epigallocatechin-3-gallate (EGCG) is the most prominent catechin in green tea.
      EGCG has been shown to modulate numerous molecular targets in the setting of
      inflammation and cancer. These molecular targets have also been demonstrated to
      be important participants in reperfusion injury, hence this study examines the
      effects of EGCG in myocardial reperfusion injury. Male Wistar rats were subjected
      to myocardial ischemia (30 min) and reperfusion (up to 2 h). Rats were treated
      with EGCG (10 mg/kg intravenously) or with vehicle at the end of the ischemia
      period followed by a continuous infusion (EGCG 10 mg/kg/h) during the reperfusion
      period. In vehicle-treated rats, extensive myocardial injury was associated with
      tissue neutrophil infiltration as evaluated by myeloperoxidase activity, and
      elevated levels of plasma creatine phosphokinase. Vehicle-treated rats also
      demonstrated increased plasma levels of interleukin-6. These events were
      associated with cytosol degradation of inhibitor kappaB-alpha, activation of
      IkappaB kinase, phosphorylation of c-Jun, and subsequent activation of nuclear
      factor-kappaB and activator protein-1 in the infarcted heart. In vivo treatment
      with EGCG reduced myocardial damage and myeloperoxidase activity. Plasma IL-6 and
      creatine phosphokinase levels were decreased after EGCG administration. This
      beneficial effect of EGCG was associated with reduction of nuclear factor-kB and
      activator protein-1 DNA binding. The results of this study suggest that EGCG is
      beneficial for the treatment of reperfusion-induced myocardial damage by
      inhibition of the NF-kappaB and AP-1 pathway.

PMID- 15502884
TI  - [Methods of airway management in prehospital emergency medicine].
AB  - In the majority of emergency situations definite airway control can be achieved
      by endotracheal intubation with or without preceding bag valve mask ventilation.
      However, both techniques can fail because of many different reasons. Therefore,
      alternative techniques for routine anaesthesia and emergency situations are
      required. In the present article difficulties that may arise using bag valve mask
      ventilation and endotracheal intubation are discussed and an overview of
      available alternatives is given.

PMID- 15502885
TI  - [Main determinants of liver microcirculation during systemic inflammation].
AB  - More than 50% of all patients on intensive care units acquire a systemic
      inflammation such as systemic inflammatory response syndrome (SIRS) or sepsis.
      The development of hepatic microcirculatory failure with consecutive organ damage
      might occur during the course of the systemic inflammation. The liver
      microcirculation is regulated by a complex network of cellular components and
      specific mediators. The perfusion in liver sinusoids is regulated by the tonus of
      the contractile Ito cells. Nitric oxide (NO) and carbon monoxide (CO) influence
      each other and cause the Ito cells to dilate while endothelin results in a
      contraction of the Ito cells. On-going studies are investigating the role of
      angiotensin II, catecholamines and prostaglandins for the regulation of the
      hepatic microcirculatory system during systemic inflammation. Some investigations
      aim to determine the impact of sedatives and analgesics on the hepatic
      microcirculation in sepsis and SIRS. Therefore, a decisive recommendation about
      the choice and dosage of sedatives and analgesics for these patients is not
      possible. Nevertheless, ketamine, midazolam and fentanyl with their potential
      anti-inflammatory properties seem to be suitable for patients with systemic
      inflammation.

PMID- 15502887
TI  - [Defect coverage and reconstruction of thumb sensibility with the first dorsal
      metacarpal artery flap].
AB  - INTRODUCTION: The "Foucher" flap is a pedicled neurovascular island flap of the
      first dorsal metacarpal artery. METHODS: From 1992 to 2000, thirty-three
      neurocutaneous island flaps from the dorsal aspect of the index finger (FDMCA
      flap) were performed for defect coverage and reconstruction of sensibility in the
      thumb. RESULTS: Static 2-PD over the flap area averaged 10.8 mm (range 4-15),
      compared to 8.2 mm (4-15) over the dorsal aspect of the contralateral index
      finger. Response to the SW monofilaments showed no difference to normal skin or
      only diminished light touch in 76% (19/25) patients. Seventy-six percent (19/25)
      were able to return to their previous jobs or resume previous activities.
      CONCLUSION: Based on negligible donor site morbidity of the flap and the good
      sensate quality and aesthetic appearance, the Foucher flap has become our first
      choice in defect coverage and restoration of sensibility of the thumb.

PMID- 15502888
TI  - [Plastic reconstructive therapy for postoncologic defect wounds in the pelvis].
AB  - Surgical or multimodal therapy of tumors of the pelvis often results in complex
      defects leading to functional and structural deficits, with the inability to sit
      or even lie without pain. Multimodal therapy may cause induration of soft tissues
      and muscles, obstruction of the small bowel, fistulas, and infected cavities.
      Early soft tissue reconstruction, preferably with myocutaneous flaps, reduces
      postoperative problems in these patients by early coverage of defects, closure of
      cavities, and prevention of wound healing complications and therefore allows
      earlier rehabilitation.

PMID- 15502889
TI  - [Conventional and minimally invasive surgical methods for gastroesophageal
      reflux].
AB  - The introduction of minimally invasive techniques has had great influence on the
      indication and surgical therapy for gastroesophageal reflux disease. This
      analysis is an overview of the current evidence-based status and a critical
      reprisal of open and laparoscopic antireflux surgery. RESULTS: The analysis of
      randomized trials showed an advantage for patients after laparoscopy for total
      and partial fundoplication because of reduced morbidity, shorter postoperative
      hospitalization due to faster recovery, and significantly fewer scar and wound
      problems. The functional results of open and laparoscopic techniques were
      similar. Five-year follow-up results for the latter showed effective reflux
      control in at least 85% of patients. Randomized trials regarding technical
      variations did not show an advantage for division of the short gastric vessel. A
      bougie for the cardia calibration can prevent postoperative dysphagia after
      fundoplication.

PMID- 15502890
TI  - [Submucosal infiltration and local recurrence in pT1 low-risk rectal cancer
      treated by transanal endoscopic microsurgery].
AB  - BACKGROUND: The association between submucosal infiltration and tumor recurrence
      was analyzed by long-term follow-up of patients with pT1 "low risk" rectal
      carcinoma. PATIENTS AND METHODS: Forty patients with pT1 rectal cancer of the
      upper and middle rectum were treated by transanal endoscopic microsurgery. All
      carcinomas fulfilled the low-risk criteria, and were completely resected. No
      further treatment was carried out. Follow-up data were available for all 40
      patients, with a median follow-up of 5.4 years. RESULTS: Two patients (5.0%)
      developed local tumor recurrence after 14 and 18 months, respectively, and had
      curative rectal resection after neoadjuvant radiochemotherapy. In the histology
      of the initial specimens, both patients had deep submucosal infiltration (sm3).
      Another patient, primarily sm2 without local recurrence, developed a metachronous
      singular liver metastasis which was curatively resected. The risk of developing a
      recurrent tumor was significant for sm3 carcinomas (sm1+sm2 vs sm3, P=0.046).
      CONCLUSION: Transanal endoscopic microsurgery is an excellent method of treating
      low-risk pT1 carcinomas of the rectum. Deep submucosal infiltration (sm3) seems
      to be an additional high-risk factor for developing local recurrence.

PMID- 15502891
TI  - [Twelve years of laparoscopic cholecystectomy].
AB  - We studied developments in indication, operation time, conversion rate,
      morbidity, and mortality from the beginning of laparoscopic cholecystectomy.
      Between 1990 and 2002 we prospectively evaluated 4498 patients undergoing
      cholecystectomy (CE), of whom 79% were treated laparoscopically (lap). In 6.6%,
      the procedure had to be converted from laparoscopic to open cholecystectomy
      (con), and 14% were performed open from the beginning (open). During the above
      time period, the rate of open CE decreased steadily (49% in 1990 to 7.2% in
      2002). The average operation time of lap CE remained constant with an average of
      74 min (range 20-330). The conversion rate decreased in spite of broader
      indication for lap CE in even more complicated gallstone diseases, from an
      initial 9.4% to 2.5%. Among intraoperative complications in lap and con, bile
      duct lesions remained constant with 5/3856 (0.1%), bleeding which led to
      conversion decreased from 1.9% to 0.3%, and the rate of gall bladder perforation
      increased from 12% to 20.5%. Thirty-day morbidity was 2% in lap CE, 5% in con,
      and 11.5% in open. The mortality was 0% in lap, 0.7% in con, and 1% in open.
      CONCLUSION: Since the introduction of laparoscopic cholecystectomy the indication
      for this minimal-invasive operation steadily increased, the conversion-rate
      decreased and the complication-rate could be held low. Even with fast
      laparoscopic experience 7% of all cholecystectomies are technically difficult and
      remain to be carried out primarily in an open technique. The laparoscopic
      cholecystectomy has become the gold standard in the therapy of gallstone disease.

PMID- 15502893
TI  - [Assessment of motivational changes in tinnitus sufferers. A study of the
      transtheoretical model].
AB  - OBJECTIVES: Cognitive-behavioural treatment of chronic tinnitus needs active
      cooperation and motivation in patients. The transtheoretical model (TTM) defines
      the behavioural change using six different stages of change (SoC). In this study,
      we examined SoC in patients with tinnitus via a new self-rating instrument.
      SAMPLE AND METHODS: An item-pool, consisting of 48 questions, was administered to
      125 tinnitus sufferers in a cross-sectional study. In addition to data on
      tinnitus history, the tinnitus strain (THI, German: TB-12), scores of anxiety and
      depression (HADS-D), and life quality (SF-12) were assessed. RESULTS: Four SoC
      could be identified empirically: (1) precontemplation, (2)
      contemplation/preparation, (3) action/maintenance, and (4) termination.
      Associations of the SoC with socio-demographic and tinnitus related data, as well
      as with the instruments applied, conformed with the theory. CONCLUSIONS: The
      results confirm the transfer of SoC theory to patients with tinnitus.

PMID- 15502894
TI  - [Postoperative pain therapy after tonsillectomy in children. An observational
      study for 7 days].
AB  - OBJECTIVE: We investigated the efficacy and side-effects of a concept for pain
      therapy after tonsillectomy in children. PATIENTS AND METHODS: A total of 100
      children aged between 6 and 14 years were treated according to the following
      protocol for pain therapy after tonsillectomy: after induction of anaesthesia the
      children received 35-40 mg/kg acetaminophen rectally and 0.1 mg/kg piritramide
      i.v.. Additionally, boluses of 0.05 mg/kg pitritramide i.v. were allowed in the
      recovery room and 2 doses of 20 mg/kg acetaminophen were given rectally every 6 h
      on the day of surgery. On the following day the children received 30 mg/kg
      acetaminophen 3 times per day and from the second postoperative day onwards 1
      mg/kg diclofenac was given 3 times a day. The rescue therapy was 5 mg/kg
      metamizol orally. The severity of the postoperative pain was evaluated by a
      visual pain scale (VAS) (0-100), side-effects such as vomiting and postoperative
      haemorrhage were documented. The Friedman test was used for testing the time
      course of pain intensity. RESULTS: The median of the VAS was 42 on the day of
      surgery, 35 on the first postoperative day and fell continuously to 10 by the 6th
      postoperative day. The decrease of pain severity was statistically significant (p
      <0.05). A rescue therapy was necessary in 6 patients on the day of surgery and in
      9 patients on the first postoperative day. 7 patients suffered a postoperative
      haemorrhage, 4 out of the 7 needed a surgical revision and 2 out of 100 patients
      vomited. CONCLUSION: We conclude that this protocol for pain therapy after
      tonsillectomy was effective. The incidence of postoperative haemorrhage and
      vomiting was low.

PMID- 15502895
TI  - [Congenital hearing loss. Molecular genetic diagnosis of connexin genes and
      genetic counselling].
AB  - BACKGROUND: About 50% of congenital non-syndromic hearing impairment is caused by
      genetic factors. Research on the genetics of deafness has revealed a vast number
      of relevant genes. Mutations in the GJB2 gene have been shown to be the most
      common in several populations. METHODS: Mutation analysis of the genes for
      connexin 26, 30 and 31 (GJB2, GJB6 and GJB3) was performed in 67 patients with
      profound hearing loss. RESULTS: Of the participants, 9% had two pathogenic
      mutations in the GJB2 gene. Pedigree information indicates that in these families
      further offspring have a 25% to a 100% chance of having hearing impairment.
      CONCLUSIONS: Patients with non-syndromic hearing impairment should be offered
      molecular diagnostics of the GJB2 gene. Genetic counseling is mandatory for
      mutation carriers in order to advise them on the individual consequences of the
      gene test results.

PMID- 15502896
TI  - [Warping of the soft palate].

PMID- 15502897
TI  - [Prion diseases].

PMID- 15502898
TI  - [Cardiovascular risk in the "Women's Health Initiative". Much ado about
      nothing?].

PMID- 15502899
TI  - [Bone marrow transplantation. Indications, chances and perspectives].
AB  - The hematopoietic stem cell transplantation has become an essential part of the
      treatment regimens in patients with acute and chronic leukemias, myelodysplastic
      syndromes, malignant lymphomas, multiple myeloma, and aplastic anemia. The
      decision to transplant depends on the stage of the disease, presence of risk
      factors, and age of the patient and should be taken by experienced
      hematologists/oncologists. Advances in immunogenetics have improved the treatment
      results of unrelated marrow donor transplantations. Better supportive care,
      modified conditioning regimens, and special graft preparations allow an
      allogeneic transplantation up to an age of 60 to 65 years, an autologous
      transplantation at an even higher age.

PMID- 15502900
TI  - [Bone healing in drill hole defects in spontaneously diabetic BB/OK rats. A
      histomorphometric and biomechanical study].
AB  - The objective of this study was to examine changes in the histomorphometric and
      mechanical evaluation of the influence of the diabetic metabolic state on defect
      healing depending on the defect size in spontaneously diabetic
      BB/O(ttawa)K(arlsburg) rats. Based on blood glucose levels and postoperative
      insulin requirements, 120 spontaneously diabetic BB/OK rats were divided into
      groups with well-compensated or poorly compensated metabolic state. Sixty LEW.1A
      rats served as the normoglycemic controls. Bone defects of different sizes were
      created proximal to the knee joint space and then allowed to heal for 2, 4, and 6
      weeks. Bone defect sizes > or =0.8 mm showed significant differences in the
      structural calculations and bone defect sizes > or =1.2 mm showed a significant
      decrease of all fluorochrome-based parameters of mineralization exclusively in
      the rats with poorly compensated diabetic metabolic state as well as
      significantly decreased values of biomechanical properties in comparison to the
      spontaneously diabetic rats with well-compensated metabolic states and to the
      control rats. Bone repair of minor bone defects is independent of the diabetic
      metabolic state in the spontaneously diabetic BB/OK rats. With controlled insulin
      therapy and resultant well-compensated diabetic metabolic state, severe
      mineralization and biomechanical disorders in healing of larger bone defects in
      the poorly compensated diabetic metabolic state of the experimental animal can be
      avoided.

PMID- 15502901
TI  - [Eyebrow injuries. Classification and therapy concept].
AB  - The aim of primary treatment for eyebrow injuries should be preservation of the
      original eyebrow under any circumstances. Debridement should be kept to a minimum
      even when the wound is severe. The treatment of total or partial loss of an
      eyebrow concerning the exact reconstruction of details and aesthetic aspects is a
      challenge for the surgeon. The therapy option depends on the type of eyebrow
      selected for reconstruction. We present a classification for eyebrow injuries,
      which considers type and size of defects. Based on this, different techniques and
      methods of reconstruction are recommended. Advantages and disadvantages are
      discussed and illustrated by several examples.

PMID- 15502902
TI  - Similar policing rates of eggs laid by virgin and mated honey-bee queens.
AB  - Worker-policing is a well-documented mechanism that maintains functional worker
      sterility in queen-right honey-bee colonies. Unknown, however, is the source of
      the egg-marking signal that is thought to be produced by the queen and used by
      policing workers to discriminate between queen- and worker-laid eggs. Here we
      investigate whether mating is necessary for the queen to produce the egg-marking
      signal. We compare the removal rate of eggs laid by virgin queens and compare
      this rate with that of eggs laid by mated queens. Our results show that mating
      does not affect the acceptability of eggs, suggesting that physiological changes
      linked to the act of mating do not play a role in the production of the queen's
      egg-marking signal.

PMID- 15502903
TI  - Gluconic acid production and phosphate solubilization by the plant growth
      promoting bacterium Azospirillum spp.
AB  - In vitro gluconic acid formation and phosphate solubilization from sparingly
      soluble phosphorus sources by two strains of the plant growth-promoting bacteria
      A. brasilense (Cd and 8-I) and one strain of A. lipoferum JA4 were studied.
      Strains of A. brasilense were capable of producing gluconic acid when grown in
      sparingly soluble calcium phosphate medium when their usual fructose carbon
      source is amended with glucose. At the same time, there is a reduction in pH of
      the medium and release of soluble phosphate. To a greater extent, gluconic acid
      production and pH reduction were observed for A. lipoferum JA4. For the three
      strains, clearing halos were detected on solid medium plates with calcium
      phosphate. This is the first report of in vitro gluconic acid production and
      direct phosphate solubilization by A. brasilense and the first report of P
      solubilization by A. lipoferum. This adds to the very broad spectrum of plant
      growth-promoting abilities of this genus.

PMID- 15502905
TI  - [White matter lesions as a risk factor for stroke and dementia. A population
      based study in 85-year-olds].
AB  - AIM: This study was performed to determine whether white matter lesions on
      cranial computed tomography (cCT) are associated with increased prevalence and
      incidence of stroke, dementia, and mortality. METHODS: A representative sample of
      239 85-year-olds living in Gothenburg, Sweden, was examined in a population-based
      study. Stroke was defined by information from patient reports, key informants,
      and an inpatient register system. Dementia was diagnosed according to DSM-III-R.
      White matter lesions (WML) and infarcts were determined by cCT. Follow-up
      examinations were performed 3 years later. RESULTS: White matter lesions doubled
      the odds of previous stroke (OR 1.8, 95% CI 1.03-3.3). Individuals with WML and
      stroke showed higher prevalence of dementia (OR 16.5, 95% CI 6.5-41.8) and
      mortality (OR 12.4, 95% CI 5.1-30.0) than those without WML and stroke.
      CONCLUSION: White matter lesions are common in the elderly, and these changes
      have clinical consequences increasing the risk of stroke. Whether preventive
      mechanisms could lead to risk reduction should be clarified in further studies.

PMID- 15502906
TI  - [Technique and approach to carotid stenting].
AB  - Assuming that the ongoing large randomized controlled trials comparing CAS and
      endarterectomy support the efficacy and safety of CAS, this method will play a
      major role in patients with carotid stenosis in the near future. Patient
      selection, establishing standards of treatment, and systematic training of the
      interventionist are major issues. This article aims to give an overview of
      current techniques and devices available in CAS.

PMID- 15502907
TI  - [Positron emission tomography (PET) for diagnosis and monitoring of treatment for
      urological tumors].
AB  - Positron emission tomography (PET) using ((18)F)2-fluoro-D-2-desoxyglucose (FDG)
      has been shown to be a highly sensitive and specific imaging modality in the
      diagnosis of primary and recurrent tumors and in the control of therapies in
      numerous non-urologic cancers. It was the aim of this review to validate the
      significance of PET as a diagnostic tool in malignant tumors of the urogenital
      tract. A systematic review of the current literature concerning the role of PET
      for malignant tumors of the kidney, testicles, prostate, and bladder was carried
      out. The role of FDG PET for renal cell cancer can be seen in the detection of
      recurrences after definitive local therapy and metastases. The higher sensitivity
      of PET in comparison to other therapeutic modalities (CT, ultrasound, MRI) in
      recurrent and metastatic renal cell cancer suggests a supplemental role of this
      diagnostic procedure to complement other imaging modalities.The clinical value of
      PET is established for the identification of vital tumor tissue after
      chemotherapy of seminomatous germ cell tumors. This diagnostic method has little
      significance for primary tumor staging and diagnosis of non-seminomatous germ
      cell tumor because of the high probability of false-negative results in adult
      teratomas. FDG PET is not sensitive enough in the diagnosis of primary or
      recurrent tumors in prostate or bladder cancer. Also PET did not prove to be
      superior to conventional bone scintigram in the detection of mostly osteoblastic
      metastases in prostate cancer. The recent use of alternative tracers, which are
      partly not eliminated by urinary secretion (acetate, choline) has increased the
      sensitivity and specificity of PET also in this tumor entity so that further
      clinical investigations are needed to validate these technical modifications in
      their significance for this imaging modality. PET appears to be sufficiently
      evaluated only for the diagnostic follow-up of patients with seminomatous germ
      cell tumors after chemotherapy to regard it is the diagnostic tool of first
      choice. For all other tumors of the urogenital tract this proof is still awaited.

PMID- 15502908
TI  - [New techniques in computed tomography. Significance for urology].
AB  - Computed tomographic (CT) imaging has become the modality of choice for the
      assessment of patients with urological malignancies. Recently, multi-slice CT
      imaging was introduced, providing faster acquisition times and higher resolution
      leading to improved image quality. Several studies show that thin-slice, high
      resolution acquisition strategies lead to an improved accuracy for T-staging,
      especially of renal cell carcinomas. Three-dimensional post-processing techniques
      for the visualization of the vascular supply as well as the ureter (CT
      angiography and CT-urography) are helpful for surgical planning. Compared to
      conventional imaging strategies unenhanced CT images render higher sensitivities
      and specificities for detecting stone disease in patients with acute flank pain.
      In the USA unenhanced CT imaging has almost replaced conventional urography, as
      no contrast agent is administered and the examination time is shorter. PET/CT
      examinations provide information on the morphology and function of tumors in one
      examination. However, there are only few data available for the assessment of
      urologic tumors.

PMID- 15502909
TI  - [New techniques in uro-sonography].
AB  - New sonographic techniques in urology, together with their principles of
      operation, will be presented. Together with the utilization of broadband
      ultrasound scanners and digital beam formers, leading to better spatial
      resolution and increased line density in ultrasound imaging, panorama sonography
      enables the outline of wide lateral regions independent of the width of the
      scanner. Spatial compound sonography achieves a comparatively better
      visualization of details in the b-mode image than has yet been available. The
      continuously improved 3-D, now leading to 4-D, techniques, which means real time
      capabilities, make the visualization of unrestricted imaging planes, which are
      not seen in conventional 2-D techniques, possible. The second harmonic imaging
      technique, including the special applications tissue harmonic imaging (THI) and
      contrast harmonic imaging (CHI), uses special ultrasound signal processing
      procedures for capturing and evaluating tissue hemoperfusion-here in combination
      with ultrasound contrast agents (UCA). Furthermore, microvascular imaging (MVI)
      enables the visualization of perfusion in tissues reaching the microcirculation
      regions. This leads to new possibilities for the assessment of pathological
      perfusion patterns, e.g. in andrology (perfusion of testicles) and uro-oncology
      (hyperperfusion of malignant regions).

PMID- 15502910
TI  - [Ultrasound in urogynecology].
AB  - Radiologic procedures such as lateral cystography have been substituted by
      ultrasound in urogynecology. The techniques are standardized and reproducible.
      Ultrasound is also useful for evaluating the bladder neck (funneling), the
      urethra (diverticula) and the paraurethral tissues (vaginal cysts, vaginal
      fibroids). The technique is limited in patients with genital prolapse beyond the
      hymenal ring. Advantages include the avoidance of x-rays and catherization.

PMID- 15502911
TI  - [Evidence based medicine indications for radiation therapy in testicular germ
      cell tumours].
AB  - The intensity of adjuvant radiotherapy for stage I seminoma could be reduced
      substantially in recent years, achieving cure with low side effects and a low
      probability of late complications. Today a dose of 20 Gy is applied to the para
      aortic lymphatics. Valuable treatment alternatives to radiotherapy have emerged:
      surveillance strategy allows 80% of patients to avoid further treatment. However,
      the remaining 20% will be exposed to potentially more intensive salvage therapy.
      Adjuvant carboplatinum chemotherapy offers similar disease-free survival to
      adjuvant radiotherapy. Long-term experience with late toxicity is not available.
      In seminoma CS IIA/B curative irradiation remains the standard treatment. Brain
      metastases of testicular germ cell tumors are treated with a combination of
      chemotherapy and cranial irradiation. In intratubular germ cell neoplasia (TIN),
      radiotherapy with 20 Gy will safely eliminate all TIN loci, but will destroy
      potential residual fertility.

PMID- 15502912
TI  - Development of candidate introgression lines using an exotic barley accession (
      Hordeum vulgare ssp. spontaneum) as donor.
AB  - In the present paper, we report on the selection of two sets of candidate
      introgression lines (pre-ILs) in spring barley. Two BC2DH populations, S42 and
      T42, were generated by introgressing an accession of Hordeum vulgare ssp.
      spontaneum (ISR42-8, from Israel) into two different spring barley cultivars,
      Scarlett (S) and Thuringia (T). From these BC2DH populations two sets with 49
      (S42) and 43 (T42) pre-ILs were selected, and their genomic architecture as
      revealed by SSR marker analysis was characterised. The selected pre-ILs cover at
      least 98.1% (S42) and 93.0% (T42) of the exotic genome in overlapping
      introgressions and contain on average 2 (S42) and 1.5 (T42) additional non-target
      introgressions. In order to illustrate a potential application and validation of
      these pre-ILs, the phenotypic effect of the exotic introgression at the locus of
      the major photoperiod response gene Ppd-H1 was analysed. Pre-ILs carrying the
      introgression at the Ppd-H1 locus flowered significantly earlier than the elite
      parents, and the introgression maintained its effect across the two genetic
      backgrounds and across four tested environments. The selected pre-ILs represent a
      first promising step towards the assessment and utilization of genetic variation
      present in exotic barley. They may promote the breeding progress, serve for the
      verification of QTL effects and provide a valuable resource for the unravelling
      of gene function, e.g. by expression profiling or map-based cloning.

PMID- 15502913
TI  - Construction of a linkage map based on a Lathyrus sativus backcross population
      and preliminary investigation of QTLs associated with resistance to ascochyta
      blight.
AB  - A linkage map of the Lathyrus sativus genome was constructed using 92 backcross
      individuals derived from a cross between an accession resistant (ATC 80878) to
      ascochyta blight caused by Mycosphaerella pinodes and a susceptible accession
      (ATC 80407). A total of 64 markers were mapped on the backcross population,
      including 47 RAPD, seven sequence-tagged microsatellite site and 13 STS/CAPS
      markers. The map comprised nine linkage groups, covered a map distance of 803.1
      cM, and the average spacing between markers was 15.8 cM. Quantitative trait loci
      (QTL) associated with ascochyta blight resistance were detected using single
      point analysis and simple and composite interval mapping. The backcross
      population was evaluated for stem resistance in temperature-controlled growth
      room trials. One significant QTL, QTL1, was located on linkage group 1 and
      explained 12% of the phenotypic variation in the backcross population. A second
      suggestive QTL, QTL2, was detected on linkage group 2 and accounted for 9% of the
      trait variation. The L. sativus R-QTL regions detected may be targeted for future
      intergenus transfer of the trait into accessions of the closely related species
      Pisum sativum.

PMID- 15502914
TI  - Inheritance of evolved glyphosate resistance in Conyza canadensis (L.) Cronq.
AB  - N-(phosphonomethyl)glycine (glyphosate) resistance was previously reported in a
      horseweed [Conyza (=Erigeron) canadensis (L.) Cronq.] population from Houston, DE
      (P (0) (R) ). Recurrent selection was performed on P (0) (R) , since the
      population was composed of susceptible (5%) and resistant (95%) phenotypes. After
      two cycles of selection at 2.0 kg ae glyphosate ha(-1), similar glyphosate rates
      that reduced plant growth by 50%, glyphosate rates that inflicted 50% mortality
      in the population, and accumulations of half of the maximum detectable shikimic
      acid concentration were observed between the parental P (0) (R) and the first
      (RS(1)) and second (RS(2)) recurrent generations. In addition, RS(1) and RS(2)
      did not segregate for resistance to glyphosate. This suggested that the RS(2)
      population comprised a near-homozygous, glyphosate-resistant line. Whole-plant
      rate responses estimated a fourfold resistance increase to glyphosate between
      RS(2) and either a pristine Ames, IA (P (0) (P) ) or a susceptible C. canadensis
      population from Georgetown, DE (P (0) (S) ). The genetics of glyphosate
      resistance in C. canadensis was investigated by performing reciprocal crosses
      between RS(2) and either the P (0) (P) or P (0) (S) populations. Evaluations of
      the first (F(1)) and second (F(2)) filial generations suggested that glyphosate
      resistance was governed by an incompletely dominant, single-locus gene (R allele)
      located in the nuclear genome. The proposed genetic model was confirmed by back
      crosses of the F(1) to plants that arose from achenes of the original RS(2), P
      (0) (P) , or P (0) (S) parents. The autogamous nature of C. canadensis, the
      simple inheritance model of glyphosate resistance, and the fact that heterozygous
      genotypes (F(1)) survived glyphosate rates well above those recommended by the
      manufacturer, predicted a rapid increase in frequency of the R allele under
      continuous glyphosate selection. The impact of genetics on C. canadensis
      resistance management is discussed.

PMID- 15502916
TI  - To: Weets I, Kaufman L, Van der Auwera B et al. (2004) Seasonality in clinical
      onset of type 1 diabetes in Belgian patients above the age of 10 is restricted to
      HLA-DQ2/DQ8-negative males, which explains the male to female excess in
      incidence.

PMID- 15502917
TI  - Encephalomyocarditis-virus-induced diabetes model resembles "fulminant" type 1
      diabetes in humans.

PMID- 15502918
TI  - Sustained glucose-stimulated insulin secretion in mouse islets is not culture
      dependent.

PMID- 15502919
TI  - Taurine supplement in early life altered islet morphology, decreased insulitis
      and delayed the onset of diabetes in non-obese diabetic mice.
AB  - AIMS/HYPOTHESIS: We hypothesised that nutritional taurine, which is important for
      the development of the endocrine pancreas and reduces cytokine-induced apoptosis
      in pancreatic beta cells, would prevent or delay the onset of autoimmune
      diabetes, if given early in life to the non-obese diabetic (NOD) mouse. METHODS:
      Pregnant NOD mice received a diet supplemented with taurine throughout gestation
      or until weaning, and the pancreas of the offspring was examined using
      immunohistochemistry. This was done at postnatal day 14 and after 8 weeks
      (assessment of insulitis). The animals were also monitored until they became
      diabetic. RESULTS: At 14 days, pancreatic islet mass was significantly greater in
      animals treated with taurine than in controls. This finding was associated with a
      greater incidence of islet cell proliferation and a lower incidence of apoptosis.
      At age 8 weeks the number of islets manifesting insulitis was reduced by more
      than half, and the area of insulitis was reduced by 90%. Taurine treatment
      delayed the mean onset time of diabetes from 18 to 30 weeks in females, and from
      30 to 38 weeks in males, while 20% of treated females remained free of diabetes
      after one year. CONCLUSIONS/INTERPRETATION: Taurine supplementation in early life
      altered islet development, reduced insulitis and delayed the onset of diabetes in
      NOD mice.

PMID- 15502920
TI  - The postprandial state does not impair endothelial function in women with type 2
      diabetes irrespective of glycaemic control.
AB  - AIMS/HYPOTHESIS: The postprandial state has been shown to be associated with
      endothelial dysfunction, a predictor of cardiovascular morbidity. In type 2
      diabetes, postprandial metabolic excursions are prolonged and exaggerated, but
      less pronounced if glycaemic control is optimised. We investigated the impact of
      improved glycaemic control on endothelial function in the postprandial state.
      METHODS: We studied 19 postmenopausal women with type 2 diabetes and ten non
      diabetic subjects. Participants with diabetes were re-studied 3 months after
      intensive glucose regulation. We measured forearm blood flow by strain gauge
      plethysmography during rest, during acetylcholine infusion and post ischaemia in
      the fasting state, and again 3 hours after a mixed meal (660 kcal, 55% fat).
      RESULTS: Endothelium-dependent vasodilation was impaired in the diabetic group
      (p<0.005) and improved following an HbA1c reduction of 0.96% (p<0.05 for high
      dose acetylcholine infusion). Postprandial metabolic excursions were higher in
      the diabetic group (p<0.001, p<0.01 and p<0.05 for glucose, insulin and
      triglycerides respectively). Resting forearm blood flow increased in all groups
      after the meal (p<0.005). There was no difference in fasting and postprandial
      endothelium-dependent vasodilation before and after improved glucose regulation
      in either group. CONCLUSIONS/INTERPRETATION: The postprandial state does not
      impair endothelial function in non-diabetic women and does not make pre-existing
      endothelial dysfunction worse in women with type 2 diabetes, irrespective of
      glycaemic control.

PMID- 15502921
TI  - Cellular basis of diabetic nephropathy: III. In vitro GLUT1 mRNA expression and
      risk of diabetic nephropathy in type 1 diabetic patients.
AB  - AIMS/HYPOTHESIS: Altered glucose transporter expression has been implicated in
      the pathogenesis of diabetic nephropathy. There is increasing evidence that
      genetic factors convey risk of, or protection from, diabetic nephropathy and that
      the behaviour of cultured skin fibroblasts from type 1 diabetic patients may
      reflect these genetic influences. This study aimed to compare GLUT1 mRNA
      expression levels in skin fibroblasts from type 1 diabetic patients with either
      rapid ("fast-track", n=25) or slow ("slow-track", n=25) development of diabetic
      nephropathy and from non-diabetic normal control subjects (controls, n=25).
      METHODS: Skin fibroblasts were cultured in Dulbecco's Modified Eagle's Medium
      with 25 mmol/l glucose for 36 h. Total RNA was isolated, and GLUT1 mRNA levels
      were estimated by microarray analysis and RT-PCR. RESULTS: Levels of GLUT1 mRNA
      expression in skin fibroblasts from "slow-track" patients were greater than those
      from "fast-track" patients (p=0.02), as initially detected by microarray. GLUT1
      mRNA expression levels were confirmed by RT-PCR to be higher in skin fibroblasts
      from "slow-track" patients (4.59+/-2.04) than in those from "fast-track" patients
      (3.34+/-1.2, p=0.02), and were also higher than in skin fibroblasts from control
      subjects (3.52+/-1.66, p=0.03). There was no statistically significant difference
      between levels of expression in the "fast-track" patients and the control
      subjects. CONCLUSIONS/INTERPRETATION: This finding is consistent with the
      presence of cellular protection factors against diabetic nephropathy in the "slow
      track" patients. These factors could be associated with the regulation of the
      GLUT1 pathway and may be genetically determined.

PMID- 15502922
TI  - Impaired glucose tolerance is accompanied by decreased insulin sensitivity in
      tissues of mice implanted with cells that overexpress resistin.
AB  - AIM/HYPOTHESIS: Resistin, the expression of which is suppressed by
      thiazolidinedione treatment in adipocytes, is one of the key molecules for the
      tight link between adiposity and insulin resistance. Here, we show the in vivo
      effects of resistin on insulin sensitivity in mature mice using a cell
      implantation method. METHODS: Resistin cDNA was transfected into 3T3-L1 pre
      adipocytes, which were then implanted into subcutaneous areas of nude mice.
      Metabolic analyses were performed 4 or 6 weeks after implantation. RESULTS: The
      mice implanted with 3T3-L1 cells overexpressing resistin (R-mice) showed
      significantly (p<0.05) increased plasma resistin levels. After a glucose load
      plasma insulin levels were significantly greater in R-mice than in mice implanted
      with mock-transfected cells (M-mice). The AUC of insulin after glucose loading
      was positively correlated with circulating resistin levels. Significantly
      decreased glucose responses after insulin injection were observed in R-mice,
      compared to M-mice. The insulin-induced phosphorylation level of IRS-1 was
      significantly lower in muscles of R-mice than M-mice. The expression of TNF-alpha
      mRNA in intra-peritoneal fat tissues was significantly greater in R-mice than in
      M-mice, but there was no difference between the two groups with regard to
      subcutaneous fat tissues. The concentration of TNF-alpha in plasma was positively
      correlated with resistin levels in R-mice. CONCLUSIONS/INTERPRETATION: Resistin,
      when actually secreted from cells in mature mice, causes disturbed glucose
      metabolism, possibly based on decreased insulin sensitivity in muscle. The in
      vivo effects of resistin on insulin sensitivity might be in part mediated by
      increased TNF-alpha expression in visceral fat tissues.

PMID- 15502923
TI  - N-acetyl-cysteine accelerates transfer of diabetes into non-obese diabetic scid
      mice.
AB  - AIMS/HYPOTHESIS: Type 1 diabetes mellitus is caused by autoimmune pancreatic beta
      cell destruction, and the destructive process involves several molecular
      mechanisms including oxygen-reactive species. A cysteine derivative, N-acetyl
      cysteine, is widely used as an antioxidant, but the role of N-acetyl-cysteine in
      the protection of pancreatic beta cells in type 1 diabetes remains unclear. The
      aim of this study was to clarify the effect of N-acetyl-cysteine on beta cells
      using an adoptive transfer system in a murine model of type 1 diabetes. METHODS:
      Splenocytes from diabetic female non-obese diabetic mice were transferred into
      female non-obese diabetic scid/ scid recipients to induce diabetes. Just after
      transfer, N-acetyl-cysteine was administered to non-obese diabetic scid
      recipients. Two weeks after transfer, the pancreas of the recipients was examined
      histologically, and cytokine mRNA expression in the pancreas was analysed. In
      vitro, CD4-positive splenocytes from diabetic donor mice were stimulated with
      anti-CD3 and anti-CD28 antibodies with or without N-acetyl-cysteine. RESULTS:
      Treatment with N-acetyl-cysteine significantly accelerated the transfer of
      diabetes into non-obese diabetic scid recipients. Treatment with N-acetyl
      cysteine accelerated the infiltration of mononuclear cells accompanied by CD8
      positive cells into the intra-islet region of the recipient's pancreas, and
      enhanced interferon-gamma mRNA expression in the pancreas. In vitro, treatment
      with N-acetyl-cysteine enhanced interferon-gamma and interleukin-2 production by
      CD4-positive splenocytes of the diabetic donor mice. CONCLUSIONS/INTERPRETATION:
      N-acetyl-cysteine accelerates the transfer of diabetes into non-obese diabetic
      scid mice and this effect is accompanied by the promotion of local infiltration
      and T-helper cell type 1 responses.

PMID- 15502924
TI  - Daily life activity and risk of developing impaired fasting glucose or type 2
      diabetes in middle-aged Japanese men.
AB  - AIMS/HYPOTHESIS: The aim of this study was to investigate the association between
      daily life activity and risk of developing diabetes. METHODS: The study
      population included 2924 Japanese male office workers aged 35 to 59 years who did
      not have IFG (fasting plasma glucose level 6.1-6.9 mmol/l), type 2 diabetes
      (fasting plasma glucose level > or =7.0 mmol/l and/or medication for diabetes) or
      a history of cardiovascular disease, and were not receiving medication for
      hypertension. A 1-day activity record during an ordinary weekday was used to
      estimate daily energy expenditure. Fasting glucose levels were measured at annual
      health examinations performed in May from 1994 to 2001. RESULTS: Over a 7-year
      follow-up period the relative risk of IFG and type 2 diabetes decreased with
      increasing daily energy expenditure after controlling for potential predictors of
      diabetes (p<0.001 and p=0.001 for trend respectively). The age-adjusted relative
      risk of IFG or type 2 diabetes decreased with increasing energy expenditure on
      occupational physical activity, brisk walking, riding on vehicles (standing
      position) to and from work and other physical activities (all p<0.001 for trend).
      The association with riding on vehicles (standing position) and other physical
      activities remained after controlling for other potential confounders of diabetes
      (p=0.026 and p=0.003 for trend respectively). Results of stratified analyses by
      the presence or absence of different risk factors for diabetes revealed that the
      risk of IFG or type 2 diabetes was inversely related to daily energy expenditure
      both in men at low risk of diabetes and those at high risk.
      CONCLUSIONS/INTERPRETATION: Physical activity in daily life is inversely
      associated with the risk of developing IFG or type 2 diabetes.

PMID- 15502925
TI  - Moderate alcohol intake and markers of inflammation and endothelial dysfunction
      among diabetic men.
AB  - AIMS/HYPOTHESIS: Type 2 diabetes mellitus is characterised by heightened
      inflammation and endothelial dysfunction. Moderate alcohol intake has been
      associated with a reduced risk of cardiovascular disease in type 2 diabetic
      patients. It remains to be determined whether there is an association between
      alcohol and inflammation in individuals with diabetes. METHODS: We investigated
      the relationship between alcohol intake and inflammation in 726 of 18,159 men who
      returned blood samples in the Health Professionals Follow-up Study and had
      confirmed type 2 diabetes at blood draw. RESULTS: In age-adjusted analyses,
      alcohol intake was associated with lower levels of HbA1c, fibrinogen, soluble
      tumour necrosis factor receptor-2 (sTNF-R2) and soluble vascular adhesion
      molecule-1 (sVCAM-1), and with higher levels of HDL cholesterol and adiponectin
      (p value for trends <0.05). After adjustment for age, HbA1c, insulin use, fasting
      status, smoking, BMI, physical activity, aspirin use, prevalence of
      cardiovascular disease and dietary factors, each additional drink per day was
      related to increased HDL cholesterol (0.053 mmol/l, p<0.0001) and adiponectin
      (0.8 microg/ml, p=0.01), and decreased sTNFR-2 (73 pg/ml, p=0.03), fibrinogen
      (0.302 micromol/l, p=0.02) and sVCAM-1 (33 ng/ml, p=0.02). The relationship
      between alcohol and inflammatory biomarkers persisted when subjects were
      stratified according to HbA1c levels. CONCLUSIONS/INTERPRETATION: Moderate
      alcohol intake may have a beneficial effect on markers of inflammation and
      endothelial dysfunction in type 2 diabetic patients.

PMID- 15502926
TI  - Substrates modified by advanced glycation end-products cause dysfunction and
      death in retinal pericytes by reducing survival signals mediated by platelet
      derived growth factor.
AB  - AIMS/HYPOTHESIS: Premature death of retinal pericytes is a pathophysiological
      hallmark of diabetic retinopathy. Among the mechanisms proposed for pericyte
      death is exposure to AGE, which accumulate during diabetes. The current study
      used an in vitro model, whereby retinal pericytes were exposed to AGE-modified
      substrate and the mechanisms underlying pericyte death explored. METHODS:
      Pericytes were isolated from bovine retinal capillaries and propagated on AGE
      modified basement membrane (BM) extract or non-modified native BM. The extent of
      AGE modification was analysed. Proliferative responses of retinal pericytes
      propagated on AGE-modified BM were investigated using a 5-bromo-2-deoxy-uridine
      based assay. The effect of extrinsically added platelet-derived growth factor
      (PDGF) isoforms on these proliferative responses was also analysed alongside mRNA
      expression of the PDGF receptors. Apoptotic death of retinal pericytes grown on
      AGE-modified BM was investigated using terminal deoxynucleotidyl transferase
      mediated dUTP nick end-labelling labelling, mitochondrial membrane depolarisation
      and by morphological assessment. We also measured both the ability of PDGF to
      reverse Akt dephosphorylation that was mediated by AGE-modified BM, and increased
      pericyte apoptosis. RESULTS: Retinal pericytes exposed to AGE-modified BM showed
      reduced proliferative responses in comparison to controls (p<0.05-0.01), although
      this effect was reversed at low-AGE modifications. PDGF mRNA levels were
      differentially altered by exposure to low and high AGE levels, and AGE-modified
      BM caused significantly increased apoptosis in retinal pericytes. Pre-treatment
      of AGE-modified BM with PDGF-AA and -BB reversed the apoptosis (p<0.05-0.001) and
      restored Akt phosphorylation in retinal pericytes. CONCLUSIONS/INTERPRETATION:
      Evidence suggests that substrate-derived AGE such as those that occur during
      diabetes could have a major influence on retinal pericyte survival. During
      diabetic retinopathy, AGE modification of vascular BM may reduce bioavailability
      of pro-survival factors for retinal pericytes.

PMID- 15502927
TI  - Cytokine profile and insulin antibody IgG subclasses in patients with recent
      onset type 1 diabetes treated with oral insulin.
AB  - AIMS/HYPOTHESIS: Tolerance to orally administered antigens may be generated
      through the induction of T helper cell type 2 and 3 (Th2/Th3) regulatory cells.
      We previously reported that treatment of recent onset type 1 diabetes with oral
      insulin had no effect on residual beta cell function. The aim of this study was
      to evaluate whether this treatment produces a deviation in the immune response,
      with polarisation of the cytokine pattern and the induction of a Th2-like
      antibody response. METHODS: Mononuclear cells were collected from a total of 20
      patients with type 1 diabetes before and after 12 months of treatment with oral
      insulin (n=11) or placebo (n=9). Following stimulation of the cells with insulin
      or phytohaemagglutinin, levels of Th2 and Th3 cytokines (including TGF-beta, IFN
      gamma, IL-4 and IL-5) in the culture supernatants were assessed by ELISA. In
      addition, levels of total and specific insulin antibody IgG subclasses were
      measured by radioimmunoassay in serum samples drawn from 33 patients with type 1
      diabetes before and after 3, 6 and 12 months of therapy with oral insulin (n=18)
      or placebo (n=15). RESULTS: After 12 months of treatment, the release of TGF-beta
      was significantly higher in patients who received oral insulin compared with
      those who received placebo (p=0.025 and p=0.006 for lymphocytes challenged with
      insulin and phytohaemagglutinin respectively). The two groups had similar levels
      of IL-4 and IL-5 both at baseline and after 12 months of treatment. The release
      of IFN-gamma was markedly reduced in patients treated with oral insulin compared
      with those who received placebo at the 12-month follow-up. Circulating levels of
      IgG1 and IgG3 subclasses directed against insulin were significantly lower in the
      oral insulin group than in the placebo group after 12 months of treatment (p=0.05
      for IgG1 and p=0.014 for IgG3). CONCLUSIONS/INTERPRETATION: The increased TGF
      beta release observed in patients treated with oral insulin suggests that a
      regulatory response can be induced in vivo by this treatment. The lower levels of
      insulin antibody IgG1 and IgG3 subclasses present in patients exposed to oral
      insulin are consistent with a Th2 deviation of the immune response. The failure
      of oral insulin treatment to provide any measurable clinical benefit may be due
      to the timing of treatment initiation.

PMID- 15502928
TI  - From beast to bedside: a commentary.

PMID- 15502929
TI  - Animal models have little to teach us about type 1 diabetes: 2. In opposition to
      this proposal.

PMID- 15502930
TI  - High amniotic fluid erythropoietin levels are associated with an increased
      frequency of fetal and neonatal morbidity in type 1 diabetic pregnancies.
AB  - AIMS/HYPOTHESIS: In this study we investigated whether chronic fetal hypoxia, as
      indicated by amniotic fluid erythropoietin levels, is associated with perinatal
      morbidity in type 1 diabetic pregnancies. METHODS: A total of 331 women with type
      1 diabetes had at least one childbirth between 1995 and 2000. The amniotic fluid
      erythropoietin concentration was measured in 156 diabetic singleton pregnancies
      at a median time of 1 day before Caesarean section without labour contractions
      and in 19 healthy control subjects at Caesarean section. RESULTS: The median
      amniotic fluid erythropoietin level was 14.0 mU/ml (range 2.0-1975.0) in diabetic
      pregnancies and 6.3 mU/ml (range 1.7-13.7) in controls (p<0.0001). Of the 156
      diabetic patients, 21 (13.5%) had amniotic fluid erythropoietin levels higher
      than 63.0 mU/ml. Amniotic fluid erythropoietin levels correlated negatively with
      umbilical artery pH (r=-0.49, p<0.0001) and pO2 (r=-0.62, p<0.0001) at birth and
      neonatal lowest blood glucose level (r=-0.47, p<0.0001). Positive correlations
      were found between amniotic fluid erythropoietin levels and umbilical artery pCO2
      (r=0.49, p<0.0001) and last maternal HbA1c (r=0.43, p<0.0001). Furthermore, a U
      shaped correlation was demonstrated between amniotic fluid erythropoietin levels
      and birthweight z score (z score below -0.6 SD units: r=-0.63, p=0.0007; z score
      above +1.0 SD units: r=0.32, p=0.0014). Neonatal hypoglycaemia, hypertrophic
      cardiomyopathy and admission to the neonatal intensive care unit occurred
      significantly more often in cases with high amniotic fluid erythropoietin levels
      (>63.0 mU/ml) than in those with normal levels. Multivariate logistic regression
      analysis revealed that amniotic fluid erythropoietin was the only variable
      independently related to low umbilical artery pH (<7.21; p<0.0001) and neonatal
      hypoglycaemia (p=0.002). Low umbilical artery pO2 (<15.0 mm Hg) was explained by
      amniotic fluid erythropoietin (p<0.0001) and birthweight z score (p=0.004).
      CONCLUSIONS/INTERPRETATION: Antenatal high amniotic fluid erythropoietin levels
      can identify type 1 diabetic pregnancies at increased risk of severe perinatal
      complications.

PMID- 15502931
TI  - Usefulness of B-type natriuretic peptide in elderly patients with acute dyspnea.
AB  - OBJECTIVE: Differentiating cardiogenic pulmonary edema (CPE) from respiratory
      causes of dyspnea is particularly difficult in elderly patients. The aim of our
      study was to evaluate B-type natriuretic peptide (BNP) in patients older than 65
      years presenting with acute dyspnea. DESIGN: Prospective study. SETTING: Medical
      emergency department of a 2000-bed urban teaching hospital. PATIENTS: Patients
      aged over 65 years presenting with acute dyspnea and a respiratory rate more than
      25/min or a PaO(2) below 70 mmHg, SpO(2 )less than 92%, PaCO(2) higher than 45
      mmHg with pH less than 7.35, were included. BNP levels, measured blind at
      admission were compared with the final diagnosis (CPE or no CPE) as defined by
      experts. INTERVENTION: None. MEASUREMENTS AND RESULTS: Three hundred eight
      patients (mean age of 80 years) were enrolled in the study. The median BNP was
      575 pg/ml [95% confidence interval (CI): 410-898] in the CPE group (n=141) versus
      75 pg/ml (95% CI: 59-98) in the no CPE group (n=167) (p<0.001). The best
      threshold value of BNP was 250 pg/ml, with a sensitivity and specificity for CPE
      of 0.78 (95% CI: 0.71-0.84) and 0.90 (95% CI: 0.84-0.93), respectively. The area
      under the ROC curve was 0.874+/-0.081 (p<0.001). The accuracy of BNP-assisted
      diagnosis was higher than that of the emergency physician (0.84 versus 0.77,
      p<0.05). CONCLUSION: Analysis of BNP is useful in elderly patients with acute
      dyspnea, but the threshold value is higher than that previously determined.

PMID- 15502932
TI  - Topical interleukin-8 antibody attracts leukocytes in a piglet lavage model.
AB  - OBJECTIVE: Acute respiratory distress syndrome (ARDS) in young infants is linked
      with a pulmonary inflammatory response part of which are increased interleukin-8
      (IL-8) levels and migration of polymorphonuclear leukocytes (PMNL) into lung
      tissue. A topical application of an antibody against IL-8 might therefore
      decrease PMNL migration and improve lung function. DESIGN: Randomized,
      controlled, prospective animal study. SETTING: Research laboratory of a
      university children's hospital. SUBJECTS AND INTERVENTIONS: Anesthetized,
      mechanically ventilated newborn piglets (n=22) underwent repeated airway lavage
      to remove surfactant and to induce lung inflammation. Piglets then received
      either surfactant alone (S, n=8), or a topical antibody against IL-8 admixed to
      surfactant (S+IL-8, n=8), or an air bolus injection (control, n=6). MEASUREMENTS
      AND RESULTS: After 6 h of mechanical ventilation following intervention,
      oxygenation [S 169+/-51 (SD) vs S+IL-8 139+/-61 mmHg] and lung function
      (compliance: S 1.3+/-0.4 vs S+IL-8 0.9+/-0.4 ml/cmH(2)O/kg; extra-vascular lung
      water: S 27+/-9 vs S+IL-8 52+/-28 ml/kg) were worse in the S+IL-8 group because
      reactive IL-8 production [S 810 (median, range 447-2323] vs S+IL-8 3485 (628
      16180) pg/ml; P<0.05) with facilitated migration of PMNL into lung tissue
      occurred. Moreover, antibody application caused augmented chemotactic potency of
      IL-8 [linear regression of migrated PMNL and IL-8 levels: S r(2)=0.30 (P=ns) vs
      S+IL-8 r(2)=0.89 (P=0.0002)]. CONCLUSION: Topical anti-IL-8 treatment after lung
      injury increases IL-8 production, PMNL migration, and worsens lung function in
      our piglet lavage model. This effect is in contrast to current literature using
      pre-lung injury treatment protocols. Our data do not support anti-IL-8 treatment
      in young infants with ARDS.

PMID- 15502933
TI  - Dexamethasone decreases neurological sequelae and caspase activity.
AB  - OBJECTIVE: To evaluate the use of dexamethasone in a model of meningitis-induced
      brain injury. Changes in neurobehavioral performance were the primary outcome
      variables. Changes in caspase activation and markers of neuronal injury were the
      secondary outcome variables. DESIGN: Randomized, prospective animal study.
      SETTING: University research laboratory. SUBJECTS: Male Wistar rats.
      INTERVENTIONS: Animals underwent a basilar cistern injection of either placebo or
      a suspension of Group B Streptococcus. Sixteen hours after inoculation, animals
      were randomized and received either dexamethasone or placebo in addition to
      antibiotics. Neurobehavioral performance and biological markers of brain injury
      were assessed at 3 days and 9 days after randomization. In a second experiment,
      caspase 1 and 3 were evaluated at 6 h, 24 h, and 72 h after dexamethasone
      administration. MEASUREMENTS AND MAIN RESULTS: Neurobehavioral performance at 3
      days and 9 days was significantly improved in the dexamethasone group. Serum C
      tau and cerebral edema were decreased after 3 days of dexamethasone treatment.
      Dexamethasone decreased Caspase 3 activation in meningitic animals. CONCLUSION:
      These findings demonstrate that dexamethasone decreases acute brain injury in a
      rat model of bacterial meningitis as measured by preservation of neurobehavioral
      performance.

PMID- 15502934
TI  - Dynamic microsimulation to model multiple outcomes in cohorts of critically ill
      patients.
AB  - BACKGROUND: Existing intensive care unit (ICU) prediction tools forecast single
      outcomes, (e.g., risk of death) and do not provide information on timing.
      OBJECTIVE: To build a model that predicts the temporal patterns of multiple
      outcomes, such as survival, organ dysfunction, and ICU length of stay, from the
      profile of organ dysfunction observed on admission. DESIGN: Dynamic
      microsimulation of a cohort of ICU patients. SETTING: 49Forty-nine ICUs in 11
      countries. PATIENTS: One thousand four hundred and forty-nine patients admitted
      to the ICU in May 1995. INTERVENTIONS: None. MODEL CONSTRUCTION: We developed the
      model on all patients (n=989) from 37 randomly-selected ICUs using daily
      Sequential Organ Function Assessment (SOFA) scores. We validated the model on all
      patients (n=460) from the remaining 12 ICUs, comparing predicted-to-actual ICU
      mortality, SOFA scores, and ICU length of stay (LOS). MAIN RESULTS: In the
      validation cohort, the predicted and actual mortality were 20.1% (95%CI: 16.2%
      24.0%) and 19.9% at 30 days. The predicted and actual mean ICU LOS were 7.7 (7.0
      8.3) and 8.1 (7.4-8.8) days, leading to a 5.5% underestimation of total ICU bed
      days. The predicted and actual cumulative SOFA scores per patient were 45.2 (39.8
      50.6) and 48.2 (41.6-54.8). Predicted and actual mean daily SOFA scores were
      close (5.1 vs 5.5, P=0.32). Several organ-organ interactions were significant.
      Cardiovascular dysfunction was most, and neurological dysfunction was least,
      linked to scores in other organ systems. CONCLUSIONS: Dynamic microsimulation can
      predict the time course of multiple short-term outcomes in cohorts of critical
      illness from the profile of organ dysfunction observed on admission. Such a
      technique may prove practical as a prediction tool that evaluates ICU performance
      on additional dimensions besides the risk of death.

PMID- 15502935
TI  - The effect of novelty on amphetamine self-administration in rats classified as
      high and low responders.
AB  - RATIONALE: Rats categorized as high responders (HR) based on their activity in an
      inescapable novel environment self-administer more amphetamine than low responder
      (LR) rats. Previous research has also demonstrated that novel stimuli presented
      during the amphetamine self-administration session decreases the number of
      infusions earned. OBJECTIVES: This study determined whether individual
      differences in response to inescapable or free-choice novelty differentially
      predict the ability of novel stimuli to decrease amphetamine self-administration.
      Further, this study determined whether novel stimuli maintained the ability to
      reduce self-administration with repeated presentations, and whether the effect of
      novel stimuli varied as a function of the unit dose of amphetamine tested.
      METHODS: Male rats were screened for their response in inescapable and free
      choice novelty tests. Following initial training using a high unit dose of
      amphetamine (0.1 mg/kg per infusion), the dose was reduced (0.03 mg/kg per
      infusion), and novel stimuli were presented in the operant conditioning chamber
      on four separate sessions. In experiment 2, novel stimuli were presented during
      several sessions at a variety of amphetamine doses (0.003, 0.01, 0.03, and 0.056
      mg/kg per infusion). RESULTS: Four repeated presentations of novel stimuli
      reduced amphetamine self-administration with no significant loss in the effect of
      novel stimuli across repeated presentations. In experiment 2, novel stimuli
      reduced amphetamine self-administration at low unit doses (0.003 mg/kg and 0.01
      mg/kg per infusion), and rats classified as HR based on their activity in
      inescapable novel stimuli were more disrupted by novel stimuli than LR rats.
      CONCLUSIONS: These results suggest that repeated presentation of novel stimuli
      can reduce amphetamine self-administration at low unit doses and that HR rats are
      more sensitive than LR rats to non-drug stimuli that compete with responding for
      amphetamine.

PMID- 15502936
TI  - Effects of marijuana on neurophysiological signals of working and episodic
      memory.
AB  - RATIONALE: The primary psychoactive constituent of marijuana, Delta9-THC,
      activates cannabinoid receptors, which are especially abundant in the frontal
      cortex and hippocampus. Acute marijuana smoking can disrupt working memory (WM)
      and episodic memory (EM) functions that are known to rely on these regions.
      However, the effects of marijuana on the brain activity accompanying such
      cognitive processes remain largely unexplored. OBJECTIVES: To examine such
      effects on performance and neurophysiological signals of these functions, EEG
      recordings were obtained from ten subjects (5M, 5F) performing cognitive tasks
      before and after smoking marijuana (3.45% Delta9-THC) or a placebo. WM was
      assessed with a spatial N-back task, and EM was evaluated with a test requiring
      recognition of words after a 5-10 min delay between study and test. RESULTS:
      Marijuana increased heart rate and decreased global theta band EEG power,
      consistent with increased autonomic arousal. Responses in the WM task were slower
      and less accurate after smoking marijuana, accompanied by reduced alpha band EEG
      reactivity in response to increased task difficulty. In the EM task, marijuana
      was associated with an increased tendency to erroneously identify distracter
      words as having been previously studied. In both tasks, marijuana attenuated
      stimulus-locked event-related potentials (ERPs). CONCLUSIONS: The results suggest
      that marijuana disrupted both sustained and transient attention processes
      resulting in impaired memory task performance. In subjects most affected by
      marijuana a pronounced ERP difference between previously studied words and new
      distracter words was also reduced, suggesting disruption of neural mechanisms
      underlying memory for recent study episodes.

PMID- 15502937
TI  - Rescue for rare complications of the hepatic artery in living donor liver
      transplantation using grafts of autologous inferior mesenteric artery.
AB  - This report describes two rescued cases with rare complications of the hepatic
      artery in living-donor liver transplantation (LDLT). In both cases a segment of
      the autologous inferior mesenteric artery (IMA) was successfully used as an
      arterial graft for re-vascularization under microsurgery. The first case was that
      of a pseudoaneurysm of the hepatic artery, which caused massive gastrointestinal
      bleeding. The hepatic arteries of the pre- and post-aneurysm were divided, and
      the arterial graft from the recipient's IMA was interposed for reconstruction.
      The second case was that of an intimal dissection of the recipient's hepatic
      artery. Because the dissection extended to the root of the common hepatic artery,
      the autologous IMA was interposed between the donor's hepatic artery and the
      proximal stump of the recipient's splenic artery. Reconstruction using the
      arterial graft of the autologous IMA is feasible for re-vascularization of the
      hepatic artery in liver transplantation.

PMID- 15502938
TI  - Involvement of tumor necrosis factor-alpha receptor 1 and tumor necrosis factor
      related apoptosis-inducing ligand-(TRAIL) receptor-2/DR-5, but not Fas, in graft
      injury in live-donor liver transplantation.
AB  - The pathway leading to cell death in clinical liver transplantation is not known.
      Eight liver transplant recipients and eight donors were enrolled in this study.
      Postoperative serum levels of alanine transferase had significantly increased in
      the recipients compared with those in the donors. Mild centri-lobular necrosis
      was observed in only liver tissues taken from the recipients. Tumor necrosis
      factor (TNF)-R1 and death receptor 5 expression levels had increased in liver
      tissues taken from the recipients. There were no changes in the levels of Fas/Fas
      ligand expression in liver tissues from either the donors or recipients. Tumor
      necrosis factor-related apoptosis-inducing ligand (TRAIL) expression was down
      regulated in donor liver after hepatectomy and liver allograft after
      implantation. The results suggest that, although ischemic liver injury was not
      serious, due to the short ischemia time, TNF and TRAIL signals are associated
      with liver ischemic injury in live-donor liver transplantation but Fas signal is
      not.

PMID- 15502939
TI  - Case report of unchanged tacrolimus clearance in a hypoxemic pediatric liver
      transplant recipient with hepatopulmonary syndrome.
AB  - Reductions in hepatic oxygen supply may reduce the oxidative metabolism of drugs,
      including tacrolimus. We encountered a patient (2.3-year-old girl) with hypoxemia
      [arterial oxygen tension (PaO2) 40.9 mmHg in room air] due to hepatopulmonary
      syndrome who had undergone living related liver transplantation. After
      transplantation, tacrolimus was initially administered by continuous intravenous
      infusion, and her PaO2 was maintained at more than 50 mmHg [72.8+/-10.4 (SD)
      mmHg] by oxygen supplementation. Apparent clearance of tacrolimus (calculated as:
      the infusion rate of tacrolimus/blood concentration) in the patient (0.075 l/h
      per kg) was comparable to those of non-hypoxemic control pediatric cases (0.092+/
      0.014 l/h per kg, n=7, mean age 2.2 years, PaO2 149.2+/-41.5 mmHg), except for
      the acute decline in the early period after transplantation. These findings
      suggest that the reduction in tacrolimus clearance is negligible when arterial
      oxygen tension is maintained at more than 50 mmHg, even in patients with
      hypoxemia.

PMID- 15502940
TI  - Echo-guided endomyocardial biopsy in heart transplant recipients.
AB  - After heart transplantation the effect of immunosuppression is monitored by
      histopathology of endomyocardial biopsy (EMB). EMB is usually carried out under X
      ray guidance. Between January 1998 and March 2003, 1,262 biopsies were collected
      under echo-guidance in 156 patients. The biopsy access was gained through the
      internal jugular vein, by the standard catheterization technique. The average
      time of the procedure was 17 min. Four or five specimens were obtained from each
      patient, with a success rate of 96%. Complications involved two episodes of
      partial pneumothorax in one patient, atrial flutter in another and ventricular
      fibrillation in three patients. Conversion from echo to X-ray guidance was
      indicated in 11 patients. No case of significant tricuspid regurgitation related
      to the EMB procedure was recorded. The echo-guided endomyocardial biopsy appears
      to be a prospective alternative to the conventional approach under X-ray
      guidance. Its duration is comparable, it eliminates X-ray exposure, enables
      continuous echocardiographic monitoring and can be performed at the bedside.

PMID- 15502958
TI  - Bone mineral density in Norwegian premenopausal women.
AB  - The aims of this study were: 1) to determine bone mineral density (BMD) in
      different age groups, 2) to determine the prevalence of low BMD, and 3) to
      determine the possible association between BMD and a number of risk factors in
      Norwegian premenopausal women. BMD of the lumbar spine (L(2)-L(4)), total body,
      and the hip (total femur, femur neck, and trochanter) were measured using dual
      energy X-ray absorptiometry (Prodigy, Lunar) in 145 randomly selected women aged
      13-39 years. Information on other factors thought to influence BMD was obtained
      through questionnaire and a clinical interview. The group aged 25-29 years had
      the highest mean BMD in the total body, lumbar spine, and total femur while the
      group aged 13-19 years had the highest mean BMD in the femur neck and the
      trochanter. The mean BMD values of Norwegian premenopausal women were 3.4-5.1%
      higher than US/European reference data (P<0.05). Five percent of the study sample
      aged 20-39 years were defined with low BMD (Z-score <-2) using the standard
      values from this study. Weight-bearing physical activity, body weight, body
      height, and age were positively associated with BMD, whilst menstrual dysfunction
      and previous pregnancy were associated with lower BMD in some of the measurement
      sites. The results show that the factors associated with BMD are extensive, and
      the strategies to prevent low BMD have to be multifactorial. A follow-up study
      should be conducted on the study sample to investigate actual mean BMD values and
      BMD changes through time.

PMID- 15502959
TI  - A meta-analysis of milk intake and fracture risk: low utility for case finding.
AB  - A low intake of calcium is widely considered to be a risk factor for future
      fracture. The aim of this study was to quantify this risk on an international
      basis and to explore the effect of age, gender and bone mineral density (BMD) on
      this risk. We studied 39,563 men and women (69% female) from six prospectively
      studied cohorts comprising EVOS/EPOS, CaMos, DOES, the Rotterdam study, the
      Sheffield study and a cohort from Gothenburg. Cohorts were followed for 152,000
      person-years. The effect of calcium intake as judged by the intake of milk on the
      risk of any fracture, any osteoporotic fracture and hip fracture alone was
      examined using a Poisson model for each sex from each cohort. Covariates examined
      were age and BMD. The results of the different studies were merged by using the
      weighted beta-coefficients. A low intake of calcium (less than 1 glass of milk
      daily) was not associated with a significantly increased risk of any fracture,
      osteoporotic fracture or hip fracture. There was no difference in risk ratio
      between men and women. When both sexes were combined there was a small but non
      significant increase in the risk of osteoporotic and of hip fracture. There was
      also a small increase in the risk of an osteoporotic fracture with age which was
      significant at the age of 80 years (RR = 1.15; 95% CI = 1.02-1.30) and above. The
      association was no longer significant after adjustment for BMD. No significant
      relationship was observed by age for low milk intake and hip fracture risk. We
      conclude that a self-reported low intake of milk is not associated with any
      marked increase in fracture risk and that the use of this risk indicator is of
      little or no value in case-finding strategies.

PMID- 15502960
TI  - Cortical and trabecular bone mineral density in transsexuals after long-term
      cross-sex hormonal treatment: a cross-sectional study.
AB  - The aim of this study was to explore the effect of long-term cross-sex hormonal
      treatment on cortical and trabecular bone mineral density and main biochemical
      parameters of bone metabolism in transsexuals. Twenty-four male-to-female (M-F)
      transsexuals and 15 female-to-male (F-M) transsexuals treated with either an
      antiandrogen in combination with an estrogen or parenteral testosterone were
      included in this cross-sectional study. BMD was measured by DXA at distal tibial
      diaphysis (TDIA) and epiphysis (TEPI), lumbar spine (LS), total hip (HIP) and
      subregions, and whole body (WB) and Z-scores determined for both the genetic and
      the phenotypic gender. Biochemical parameters of bone turnover, insulin-like
      growth factor-1 (IGF-1) and sex hormone levels were measured in all patients. M-F
      transsexuals were significantly older, taller and heavier than F-M transsexuals.
      They were treated by cross-sex hormones during a median of 12.5 years before
      inclusion. As compared with female age-matched controls, they showed a
      significantly higher median Z-score at TDIA and WB (1.7+/-1.0 and 1.8+/-1.1, P <
      0.01) only. Based on the WHO definition, five (who did not comply with cross-sex
      hormone therapy) had osteoporosis. F-M transsexuals were treated by cross-sex
      hormones during a median of 7.6 years. They had significantly higher median Z
      scores at TEPI, TDIA and WB compared with female age-matched controls (+0.9+/-0.2
      SD, +1.0+/-0.4 SD and +1.4+/-0.3 SD, respectively, P < 0.0001 for all) and
      reached normal male levels except at TEPI. They had significantly higher
      testosterone and IGF-1 levels (p < 0.001) than M-F transsexuals. We conclude that
      in M-F transsexuals, BMD is preserved over a median of 12.5 years under
      antiandrogen and estrogen combination therapy, while in F-M transsexuals BMD is
      preserved or, at sites rich in cortical bone, is increased to normal male levels
      under a median of 7.6 years of androgen treatment in this cross sectional study.
      IGF-1 could play a role in the mediation of the effect of androgens on bone in F
      M transsexuals.

PMID- 15502961
TI  - Image resolution and magnification using a cone beam densitometer: optimizing
      data acquisition for hip morphometric analysis.
AB  - Bone mineral density (BMD) is a primary determinant of hip fracture risk.
      However, other factors, notably the femoral geometry, can influence hip fracture
      risk. The purpose of this study was to evaluate the potential of a new cone beam
      densitometer, the DMS Lexxos, in order to visualise femoral morphometry.
      Resolution, magnification and distortion were assessed in vitro using a line pair
      test pattern and a matrix test object. Results were given in comparison with
      currently available systems: the Hologic Discovery A and the Lunar Prodigy
      densitometers. The DMS Lexxos image resolution was the same in the longitudinal
      and transversal directions evaluated between 1.4 and 0.5 line pairs/mm (lps/mm)
      for an attenuation varying from 25 to 325 mm of Perplex. The longitudinal
      resolution was evaluated between 0.9 and 0.5 lps/mm with the Hologic Discovery
      densitometer, and inferior to 0.5 with the Lunar Prodigy; as for transversal
      resolution, it varied from 0.63 to 0.5 lps/mm and from 0.6 to inferior 0.5
      lps/mm, respectively. The image was isotropic without magnification with the GE
      Lunar Prodigy, whereas there was only a transversal magnification with the
      Hologic Discovery device. The magnification was about 1.17% cm(-1 )in the two
      directions, while increasing the distance of the phantom above the examination
      table with the Lexxos. This magnification was isotropic without distortion. The
      magnification could be evaluated from two images taken before and after
      translation of the C-arm, and a magnification correction could be applied. This
      method was applied to a phantom and to a human cadaver femoral bone.

PMID- 15502962
TI  - Treatment strategies for proximal femur fractures in osteoporotic patients.
AB  - Fractures of the proximal end of the femur, together with vertebral fractures,
      are greatly exacerbated by osteoporosis and can be regarded as the most typical
      and most serious complications of this disease. The demand for prompt
      mobilisation with full loading of the affected limb, combined with a desire for
      the gentlest of treatments, becomes increasingly difficult to meet in ageing
      patients with advanced osteoporosis. The advantages of osteosynthesis in respect
      to these demands when operating on elderly patients with fractures do not apply
      due to the inability of the osteoporotic bone to hold the osteosynthetic
      components sufficiently until fracture healing occurs. This inability is related
      to the anatomy of the proximal end of the femur and its loading patterns. Under
      eccentric loading, high bending loads occur, leading to failure of the
      osteosynthetic anchorage at the center of the femoral head. This leads
      subsequently to stressful revision operations for the patient. The prosthetic
      replacement is a good option in cases of dislocated intracapsular fractures, but
      in cases of trochanteric fractures it is still debated. Therefore, it is vital
      for the trauma surgeon to have specific knowledge of the patient's bone quality
      in order to optimise the result of the preferred procedure. With reference to our
      own experimental research and a study of the current literature, this knowledge
      can be summarised as follows: the most stable anchorage for the implant is
      achieved by placing the implant through the midpoint of the femoral head (highest
      bone mineral density) or just below ("best backing"). Anchoring femoral head
      implants so that they are stable in rotation within the head-neck fragment will
      significantly raise their load bearing capacity. This is also true for
      intramedullary load bearing devices in trochanteric fractures. The distance
      between the load-bearing device in the femoral neck and the articular surface is
      inversely correlated to the stability at yield, as other studies have already
      shown. There seems to be a limit for a successful realisation of an
      osteosynthesis that lies at a femoral head bone mineral density of 250 mg/cm(3)
      calcium-hydroxyapatite (CaHAp). Nevertheless, high precision surgery in regard to
      fracture reduction and implant placement is a essential requirement for a
      successful osteosynthesis. Reproducible local measurements of bone mineral
      density and trabecular alterations, as well as quick screening methods, are very
      much desired by the authors.

PMID- 15502963
TI  - Hand workload and the metacarpal cortical index. a study of middle-aged teachers
      and dentists.
AB  - We studied load-related predictors (handedness, occupation and workload history)
      of cortical bone mass as estimated by the metacarpal cortical index (MCI). After
      being randomly selected from trade-union registers, 295 female dentists and 248
      teachers, aged 45-63 years (mean 54 years), participated in the study. The MCI
      was defined from the second metacarpal of both hands by analogue radiographs.
      Data regarding anthropometric measures, handedness, occupational exposure, number
      of pregnancies, hormonal therapy and contraceptive use, the presence of chronic
      diseases, dietary factors, smoking and leisure time physical activity were
      collected by questionnaire. Weight was measured. The dentists' workload was
      assessed in detail in 10-year periods. Multivariate methods were used in the
      statistical analysis. The metacarpal index averaged 0.62 in the right hand and
      0.61 in the left hand (P = 0.02) among the right-handed subjects, while no
      differences by hand were observed among the left-handed or mixed-handed. The MCI
      of the teachers and dentists did not differ from each other, when we controlled
      for potential confounders. The MCI decreased similarly by age in both
      occupational groups. Among the dentists, workload history was inversely
      associated with the MCI in multivariate analyses by age group. Computer use was a
      positive predictor for MCI among dentists aged 55-63 years. Occupational factors
      seem to have contradictory effects on the MCI. Too heavy or one-sided manual work
      may be deleterious for cortical bone mass.

PMID- 15502964
TI  - Surgical treatment of ankle and foot fractures in the elderly.
AB  - Ankle fractures are the most common lower extremity fractures. In younger age
      groups these fractures occur more often in men than in women, but after menopause
      there is a female predominance. Foot fractures show a similar trend. The primary
      goal in the treatment of ankle and foot fractures is to obtain exact reduction
      and stable fixation to facilitate early mobilization and good functional
      recovery. However, the need for internal fixation to secure fracture reduction
      must be weighed against the risk of operating on osteoporotic bone which lacks
      the strength to hold screws and plates. In the elderly, the preoperative
      evaluation of the peripheral blood supply is essential to avoid wound healing
      complications. We review here the surgical treatment of ankle and foot fractures
      with special reference to elderly patients.

PMID- 15502965
TI  - Degradation pathway of 2-chloroethanol in Pseudomonas stutzeri strain JJ under
      denitrifying conditions.
AB  - The pathway of 2-chloroethanol degradation in the denitrifying Pseudomonas
      stutzeri strain JJ was investigated. In cell-free extracts, activities of a
      phenazine methosulfate (PMS)-dependent chloroethanol dehydrogenase, an NAD
      dependent chloroacetaldehyde dehydrogenase, and a chloroacetate dehalogenase were
      detected. This suggested that the 2-chloroethanol degradation pathway in this
      denitrifying strain is the same as found in aerobic bacteria that degrade
      chloroethanol. Activity towards primary alcohols, secondary alcohols, diols, and
      other chlorinated alcohols could be measured in cell-free extracts with
      chloroethanol dehydrogenase (CE-DH) activity. PMS and phenazine ethosulfate (PES)
      were used as primary electron acceptors, but not NAD, NADP or ferricyanide. Cells
      of strain JJ cultured in a continuous culture under nitrate limitation exhibited
      chloroethanol dehydrogenase activity that was a 12 times higher than in cells
      grown in batch culture. However, under chloroethanol-limiting conditions, CE-DH
      activity was in the same range as in batch culture. Cells grown on ethanol did
      not exhibit CE-DH activity. Instead, NAD-dependent ethanol dehydrogenase (E-DH)
      activity and PMS-dependent E-DH activity were detected.

PMID- 15502966
TI  - Rhizobium leguminosarum methyl-accepting chemotaxis protein genes are down
      regulated in the pea nodule.
AB  - Regulation of methyl-accepting chemotaxis protein (MCP) genes of Rhizobium
      leguminosarum was studied under symbiotic conditions. Transcriptional fusions
      using both beta-galactosidase and beta-glucuronidase genes within two different
      mcp genes demonstrated that mcp expression decreased significantly during
      nodulation. Immunoblots using an anti-MCP antibody detected MCPs in free-living
      cells but not in bacteroids. Down-regulation during nodulation was not dependent
      upon known regulatory proteins involved in induction of expression of genes
      involved in nitrogen fixation. Environmental conditions found in the bacteroid
      that may trigger down-regulation were investigated by growing free-living
      cultures under a variety of growth conditions. Growth under low oxygen
      concentration or using succinate as a sole carbon source did not lower expression
      of the mcp gene fusions.

PMID- 15502967
TI  - Beta-adrenergic receptor density and adenylate cyclase activity in lead-exposed
      rat brain after cessation of lead exposure.
AB  - To understanding the reversible or irreversible harm to the beta-adrenergic
      system in the brain of lead-exposed rats, this study sets up an animal model to
      estimate the change in the sympathetic nervous system of brain after lead
      exposure was withdrawn. We address the following topics in this study: (a) the
      relationship between withdrawal time of lead exposure and brain beta-adrenergic
      receptor, blood lead level, and brain lead level in lead-exposed rats after lead
      exposure was stopped; and (b) the relationship between lead level and beta
      adrenergic receptor and cyclic AMP (c-AMP) in brain. Wistar rats were chronically
      fed with 2% lead acetate and water for 2 months. Radioligand binding was assayed
      by a method that fulfilled strict criteria of beta-adrenergic receptor using the
      ligand [125I]iodocyanopindolol. The levels of lead were determined by
      electrothermal atomic absorption spectrometry. The c-AMP level was determined by
      radioimmunoassay. The results showed a close relationship between decreasing lead
      levels and increasing numbers of brain beta-adrenergic receptors and brain
      adenylate cyclase activity after lead exposure was withdrawn. The effect of lead
      exposure on the beta-adrenergic system of the brain is a partly reversible
      condition.

PMID- 15502968
TI  - The monocyte dysfunction induced by acute tetramine poisoning and corrected by
      continuous blood purification.
AB  - The monocyte function of patients with severe tetramine poisoning and the effects
      of sequential hemoperfusion (HP) and continuous veno-venous hemofiltration (CVVH)
      on the immune status of the patients were investigated. Eleven patients with
      severe acute tetramine poisoning were treated with sequential HP and CVVH. The
      APACHE II score and Glasgow score were used to evaluate the disease status during
      the therapy. Blood samples were collected at 0, 2, 6, 12, 24, 48, and 72 h.
      Peripheral monocytes were isolated and stimulated with lipopolysaccharide (LPS)
      to detect the ability of monocytes to secrete tumor necrosis factor-alpha (TNF
      alpha), interleukin (IL)-6, and IL-10. The number of monocytes was counted at the
      same time. As expected, three patients died and the clinical manifestations were
      improved in the other patients. The production of cytokines (TNF-alpha, IL-6, and
      IL-10) by monocytes of patients with tetramine poisoning was much lower than
      normal controls (P<0.001), and was significantly increased after HP and CVVH in
      the survivors (TNF-alpha, IL-6, IL-10, P<0.05, P<0.01, P<0.05, respectively). The
      blood concentration of tetramine was 0.124+/-0.082 mg/l at prehemoperfusion and
      0.080+/-0.055 mg/l at posthemoperfusion (P<0.05). It was concluded that there was
      severe damage to monocyte function in patients with tetramine poisoning, and that
      sequential HP and CVVH can effectively ameliorated monocyte function and
      eliminate tetramine from blood.

PMID- 15502969
TI  - Hepatotoxic effects of polidocanol in a model of autologously perfused porcine
      livers.
AB  - Polidocanol is an effective sclerosing agent that consists of 95%
      hydroxypolyethoxydodecane and 5% ethyl alcohol and is known to have a low risk of
      complications. However, since the compound has been proposed for the local
      treatment of liver diseases, the potential for topical hepatic side effects
      should be examined. Therefore, the new model of normothermic-hemoperfused
      isolated porcine slaughterhouse livers was used to examine polidocanol
      hepatotoxicity encompassing the advantages of slaughterhouse organs to reduce
      animal experiments and autologous blood as an optimal perfusate. Polidocanol was
      administered via the hepatic artery and portal vein and the effects of the
      sclerosant on organ function parameters were compared with those in an untreated
      control group. In contrast to the untreated control organs, significant
      differences were found in the polidocanol group for parameters such as alanine
      aminotransferase or organ weight after perfusion. The most striking differences
      were found for hepatic bile flow, which dropped in the polidocanol group to
      0.24+/-0.02 ml/min per 1000 g after administration of the compound compared with
      3.80+/-1.08 ml/min per 1000 g in the control group. In summary, the present
      observations indicate a risk of hepatotoxic effects of polidocanol. Clinicians
      should be aware of this problem and the use of polidocanol for intrahepatic
      sclerosing should be restricted to specialized centers.

PMID- 15502970
TI  - Entacapone increases and prolongs the central effects of l-DOPA in the 6
      hydroxydopamine-lesioned rat.
AB  - Long-term palliative treatment of Parkinson's disease (PD) with the dopamine
      precursor l-3,4-dihydroxyphenylalanine ( l-DOPA, levodopa) is compromised by the
      occurrence of motor complications, most notably motor fluctuations and
      involuntary movements, l-DOPA-induced dyskinesias. This study was aimed at
      investigating the effect of adding the catechol- O-methyltransferase (COMT)
      inhibitor entacapone to chronic treatment with l-DOPA/benserazide. It was hoped
      that the administration of entacapone would prolong and smooth the central effect
      of l-DOPA exposure and that this would result in a reduced risk of l-DOPA-induced
      dyskinesia induction by lowering the l-DOPA dose. The rotational response and
      striatal extracellular dopamine release were assessed in rats that had undergone
      a unilateral 6-hydroxydopamine-induced lesion of the nigro-striatal system.
      Previous studies have shown that repeated treatment with l-DOPA is accompanied by
      a marked enhancement in behavioural responses and has pharmacological
      characteristics similar to l-DOPA-induced dyskinesia. In the present study, we
      demonstrated that rats receiving entacapone in addition to 6.50 mg/kg of l-DOPA
      displayed significant enhancement of the developing contralateral turning
      response compared with rats treated with the same dose of l-DOPA only. However,
      when reducing the l-DOPA dose to 4.25 mg/kg the behavioural response was
      comparable to that seen in rats treated with the higher dose of l-DOPA only.
      Voltammetry analysis suggests that the increased behavioural response in
      entacapone-treated rats is the result of a much larger dopamine release. In
      addition, we found that entacapone treatment prolonged and smoothed the striatal
      dopamine levels following chronic l-DOPA/benserazide treatment. From a clinical
      point of view, this finding suggests that administration of a COMT inhibitor
      should allow the frequency of l-DOPA administration to decrease and to smooth the
      brain delivery of the l-DOPA, which in the end should facilitate a reduction in
      the risk of dyskinesia induction.

PMID- 15502971
TI  - The neuroprotective effect of the antioxidant flavonoid derivate di-tert
      butylhydroxyphenyl is parallel to the preventive effect on post-ischemic Kir2.x
      impairment but not to post-ischemic endothelial dysfunction.
AB  - In the rat model of transient cerebral ischemia induced by intraluminal occlusion
      of the middle cerebral artery, we investigated the respective roles of ischemia
      and reperfusion in endothelium-dependent relaxation and smooth muscle relaxation
      related to the inward rectifier potassium current (Kir2.x), using the Halpern
      arteriography technique and/or patch-clamp technique. We first demonstrated that
      reperfusion is necessary to induce a significant impairment of smooth muscle
      Kir2.x, since ischemia alone has no effect on Kir2.x current density and
      function. In addition, we demonstrated that both ischemia and reperfusion are
      necessary for the occurrence of maximal post-ischemic endothelial dysfunction.
      The crucial role of reperfusion in post-ischemic vascular impairment prompted us
      to characterize the effect of a new antioxidant synthetic flavonoid derivate,
      3'5'di- tert-butylhydroxyphenyl (dt-BC), on both neuronal and vascular injuries.
      Dt-BC (10 mg/kg) induced a neuroprotective effect as demonstrated by a
      significant decrease in infarct size, while there was no protective effect with
      the doses of 3 mg/kg and 30 mg/kg. Parallel to neuroprotection, dt-BC at a dose
      of 10 mg/kg, but not with doses of 3 mg/kg and 30 mg/kg, prevented post-ischemic
      impairment of smooth muscle Kir2.x current density and function, while dt-BC had
      no effect on the post-ischemic alteration of endothelial function whatever doses
      are used. These data demonstrate the potential of a new synthetic flavonoid
      derivate to induce neurovascular protection and support a possible relationship
      between vascular and neuronal protection via pharmacological modulation of
      oxidative stress.

PMID- 15502974
TI  - Signals ratio method combined with wavelet transform: application to resolution
      of overlapped electrochemical signals.
AB  - A signals ratio method combined with wavelet transform was proposed for the
      resolution of a weak voltammetric signal overlapped by other components. The
      signals ratio method usually suffers from interference from noise and baseline
      contained in the original signals because these factors cause distortion of the
      signals ratio. The multiresolution capability of the wavelet transform method was
      exploited here to simultaneously remove or reduce the noise and background. As a
      result, a deformation-free signals ratio with good signal-to-noise ratio (SNR)
      was obtained even for very noisy signals. The properties of the proposed method
      were compared to other resolution methods. It was demonstrated that the combined
      signals ratio wavelet transform method was particularly applicable to resolve a
      minor component in the presence of large amount of other components, suggesting
      that it can provide improved detection limits and quantified results for minor
      components. The method was employed for the voltammetric determination of
      residual chlorine in the presence of N,N-diethyl-p-phenylenediamine (DPD).

PMID- 15502972
TI  - A six-month, placebo-controlled trial of D-cycloserine co-administered with
      conventional antipsychotics in schizophrenia patients.
AB  - RATIONALE: D-Cycloserine, a partial agonist at the glycine site of the N-methyl-D
      aspartate receptor, has demonstrated inconsistent efficacy for negative and
      cognitive symptoms of schizophrenia. The strongest evidence for efficacy has come
      from studies using D-cycloserine at a dose of 50 mg/day added to conventional
      antipsychotics in trials of 8 weeks duration or less. OBJECTIVE: To assess the
      efficacy for negative symptoms and cognitive impairment of D-cycloserine
      augmentation of conventional antipsychotics in a 6-month trial. METHODS: Fifty
      five schizophrenia patients with prominent negative symptoms, treated with
      conventional antipsychotics, were randomly assigned to treatment with D
      cycloserine 50 mg/day or placebo for 6 months in a double-blind, parallel group
      design. RESULTS: Twenty-six subjects completed the 6-month trial; drop-out rates
      did not differ between treatment groups. D-Cycloserine treatment did not differ
      from placebo treatment on any primary outcome measure at 8 or 24 weeks, including
      response of negative symptoms and performance on a cognitive battery. Serum D
      cycloserine concentrations did not correlate with response of negative symptoms.
      CONCLUSION: D-Cycloserine did not exhibit therapeutic effects in this trial,
      possibly reflecting the high drop-out rate, a narrow range of therapeutic serum
      concentrations, a modest magnitude of therapeutic effect for the selected outcome
      measures, or loss of efficacy over time. Because D-cycloserine is a partial
      agonist with relatively low affinity for the glycine site, the magnitude of
      potential therapeutic effect may be smaller than that achieved by the higher
      affinity full agonists, glycine and D-serine.

PMID- 15502975
TI  - Kinematic strategies for lowering of upper limbs during suggestions of heaviness:
      a real-simulator design.
AB  - The aim of the experiment was to study possible differences between the kinematic
      strategies for the "involuntary" arm lowering of hypnotized highly susceptible
      subjects (H-Highs) and for the voluntary movement of non-hypnotizable simulators
      (Sims) during suggestions of arm heaviness (Part I). In addition, a comparison
      between awake susceptible subjects (W-Highs) and H-Highs was carried out to
      clarify the specific role of the hypnotic state and hypnotizability (Part II).
      Subjects' absorption and attentional/imagery capabilities were evaluated through
      neuropsychological tests. Their arm movements were monitored three-dimensionally
      at hand, wrist and elbow level through a Polhemus Fastrack system. A final
      interview collected self-reports concerning the perception of movement
      involuntariness. Neuropsychological tests showed better "absorption" and imagery
      capabilities in Highs. In the interview, H-Highs perceived a higher involvement
      in the task and greater involuntariness and difficulties in contrasting the arm
      lowering than the Sims. Kinematic analysis showed significant differences between
      H-Highs and Sims for arm displacements along the vertical axis and on the
      horizontal plane. In fact, the former lowered the left arm earlier and to a
      greater degree than the right arm; on the horizontal plane, a forearm flexion was
      observed for H-Highs on the right side. On comparing W-Highs and H-Highs,
      hypnosis appeared to magnify the waking motor strategies, but also to induce
      specific changes, mainly concerning the horizontal plane. These results cannot be
      interpreted on the basis of "role playing" and socio-cognitive factors. They are
      believed to be due to a balance between the effectiveness of the frontal
      executive control towards the selection of behaviors and movement automaticity,
      which is in line with the neo-dissociation theory of hypnosis.

PMID- 15502976
TI  - Corticospinal disinhibition during dual action.
AB  - When attempting to perform two tasks simultaneously, the human motor as well as
      the cognitive system shows interference. Such interference often causes altered
      activation of the cortical area representing each task compared to the single
      task condition. We investigated changes in corticospinal inhibition during dual
      action by transcranial magnetic stimulation (TMS). Single-pulse TMS was applied
      to the left motor cortex, triggered by right leg movement (tibialis anterior
      muscle) while the right abductor digiti minimi (ADM) muscle was moderately
      activated (10-20% of the maximal voluntary contraction). The background
      electromyography (EMG) activity of ADM was measured before and during the leg
      movement. The silent period (SP) and amplitude of motor evoked potential (MEP)
      following magnetic stimulation in active ADM were compared for the conditions
      with and without leg movement. The mean area of the rectified EMG activity of ADM
      did not alter, while the SP was significantly shortened during leg movement
      compared to that without leg movement. MEP amplitude was comparable between the
      two conditions. These results suggest that corticospinal inhibition tested by the
      SP duration is reduced during the movement of another body part, presumably in
      order to help maintain muscle force by compensating interference-related
      alteration in motor cortical activation.

PMID- 15502978
TI  - Differential distribution of growth associated protein (GAP-43) in the motor
      nuclei of the adult rat conus medullaris.
AB  - GAP-43 is normally produced by neurons during developmental growth and axonal
      regeneration, but it is also expressed in specific regions of the normal adult
      nervous system. We studied the protein expression of GAP-43 within the conus
      medullaris portion of the spinal cord in adult male rats. Immunohistochemistry
      for choline acetyltransferase (ChAT) was first performed to identify specific
      efferent autonomic and motor nuclei in lumbosacral segments of the spinal cord.
      Adjacent sections were then processed for GAP-43 immunoreactivity (IR). We show
      GAP-43 IR in the superficial portion of the dorsal horn, the intermediolateral
      nucleus, and the dorsal commissural tract. We also demonstrate a differential
      distribution of GAP-43 IR between different motor nuclei of the conus medullaris.
      Using densitometry, the most prominent GAP-43 IR was detected in the dorsolateral
      and dorsomedial motor nuclei, which represent the human Onuf's nucleus homologue.
      Confocal microscopy of double immunofluorescent labeling for ChAT and GAP-43
      demonstrate GAP-43 IR in the neuropil of the autonomic and motor nuclei, and many
      of the GAP-43 IR arbors are in close apposition with the efferent cholinergic
      neurons. We note that the efferent neurons of both the autonomic and somatic
      nuclei, which are ultimately responsible for the integrated normal control of the
      lower urinary tract, bowel and sexual functions, are heavily innervated by GAP-43
      enriched projections. We speculate that these functionally related neurons retain
      a physiological GAP-43-associated synaptic plasticity throughout adult life.

PMID- 15502979
TI  - Restricting arm use enhances compensatory reactions of leg muscles during
      walking.
AB  - A number of recent studies have indicated that whole-body coordinated reactions
      are employed to regain balance following disturbances during walking. However, it
      is not always the case that all body segments are available to contribute to
      balance corrective strategies. We hypothesize that balance corrective strategies
      will adapt to task and environment constraints such that greater responses are
      generated in the available body segments when other body segments are unable to
      participate. In this study, we tested the hypothesis that voluntarily restricting
      the arms during walking would result in an increase in the amplitude of the
      electromyographic responses evoked in leg muscles when subjects are perturbed at
      the torso during walking. To do so, subjects were asked to walk on a motorized
      treadmill while either crossing their arms across their front or back, or with
      their arms swinging normally. Periodic perturbations, forwards and backwards,
      were applied at the pelvis randomly throughout the step cycle. This resulted in
      short latency responses in leg muscles. The amplitude of these responses was
      increased when subjects walked with their arms crossed, as compared with normal,
      unrestricted walking. Facilitation of these evoked responses was restricted to
      the early part of the stance phase, particularly at heel-strike. The pattern of
      muscle activation and the latency of the responses were not affected by
      restricting the arms. We suggest that this finding indicates that whole-body
      balance corrective strategies employed during walking are selected based upon the
      demands of the general features of the task, but that components of the strategy
      are scaled according to the specific context-dependent needs of the task.

PMID- 15502980
TI  - Initiation and cancellation of the human heave linear vestibulo-ocular reflex
      after unilateral vestibular deafferentation.
AB  - The effect of unilateral vestibular deafferentation (UVD) on the linear vestibulo
      ocular reflex (LVOR) was studied in 11 humans an average of 52 months following
      surgical UVD. Controls consisted of seven healthy age-matched subjects. The LVOR
      was evoked by directionally random, transient whole body interaural (heave)
      translation with a peak acceleration of 0.5 g while subjects viewed earth-fixed
      (LVOR) and head-fixed (cancellation) targets 15, 25, and 200 cm distant. The
      magnitude of the LVOR slow phase was inversely proportional to target distance
      for both subject groups. Neither latency nor the magnitude of the LVOR
      significantly differed in the ipsi- vs contralesional directions (P>0.1) in UVD.
      When the target disappeared at heave onset, subjects with UVD had LVOR slow phase
      displacement 100 ms later that was 5% of ideal at 15 cm, 6% at 25 cm, and 16% at
      200 cm. This was significantly less than corresponding control values of 41, 43,
      and 50%. During cancellation the LVOR magnitude 100 ms from heave onset was
      reduced at all target distances by an average of 40+/-4%, and the relative
      reduction did not significantly differ between controls and subjects with UVD
      (P>0.1). Cancellation latency did not vary significantly among target distances
      or subject groups. It is concluded that after UVD, the LVOR is bilaterally and
      symmetrically reduced but remains modulated by viewing distance and cancellation
      effort.

PMID- 15502981
TI  - Functional modulation of shoulder girdle stability.
AB  - We have previously reported that electrical stimulation of the ulnar nerve at
      group I strength evokes reflex excitation of the trapezius muscle in normal human
      subjects. In the present study this reflex has been evoked while subjects were
      performing a number of different tasks. When subjects performed a task involving
      a high degree of manual dexterity, the reflex was larger. On the other hand, when
      subjects performed a task that can be achieved with virtually no movement of the
      hand or wrist musculature, the reflex does not appear to show any task
      dependency. These results support the view that in delicate tasks of the hand,
      such compensatory reflexes are more important than in basic mechanisms such as
      lifting an object. The functional consequences of these findings and their
      significance in relation to the possibility that these task-related reflex gain
      changes produce intention tremor is discussed.

PMID- 15502982
TI  - Functional applications of novel Semliki Forest virus vectors are limited by
      vector toxicity in cultures of primary neurons in vitro and in the substantia
      nigra in vivo.
AB  - The Semliki Forest virus (SFV) system has been shown to be highly efficient in
      transduction of cell lines and primary cells. We employed a novel "noncytotoxic"
      SFV(PD) vector for transduction of primary ventral midbrain floor cultures in
      vitro and rat substantia nigra in vivo. Rapid protein expression was noted with
      preferential transduction of neuronal cells including the dopaminergic
      subpopulation. To examine the suitability of the SFV vector system for functional
      gene expression, SFV(PD) vectors encoding for antiapoptotic proteins Bcl-X(L) and
      XIAP were designed. Despite effective transgene expression, SFV(PD) vectors were
      unable to rescue dopaminergic neurons from MPP+-induced apoptosis. In vivo, virus
      injection into substantia nigra resulted in fast onset of transgene expression,
      but elicited an activation of microglia and an inflammation response. We conclude
      that the use of novel SFV(PD) vectors is currently limited by persistent
      neurotoxicity of the vector system. Although SFV(PD) vectors may be useful for
      protein localization studies in dopaminergic neurons, functional applications
      will require the development of even less cytopathic vector systems.

PMID- 15502983
TI  - Different corticostriatal projections from two parts of the cortical masticatory
      area in the rabbit.
AB  - The cortical masticatory area (CMA) elicits rhythmic jaw movements in response to
      repetitive stimulation and is involved in the control of mastication. Based on
      jaw movement patterns, the CMA is divided into two parts. One is the part of the
      CMA in which a T-pattern similar to jaw movements during food transport in
      natural mastication is evoked by electrical stimulation. The other is more
      dorsomedially located, and during chewing a C-pattern similar to jaw movements
      can be induced. However, it is still not known which region of the putamen
      receives projections from the CMA and whether projections originate from both
      parts of the CMA. In this study, electrophysiological and histological
      experiments were undertaken in rabbits to investigate projections from the CMA to
      the putamen. Both experiments showed that the ventral region of the putamen
      received projections from the CMA. The density of the projections from the CMA
      area inducing the T-pattern seemed to be higher than that from the area inducing
      the C-pattern. Furthermore, the peak latency of the evoked potentials from
      stimulation of the CMA area inducing the T-pattern was shorter than that from
      stimulation of the area inducing the C-pattern. The data obtained from the
      present study indicate the functional role of the ventral region of the putamen
      in the regulation of mastication, and further suggest that the corticostriatal
      pathway is involved in the transition between behavioral jaw movement patterns.

PMID- 15502984
TI  - Memory-guided saccades in Parkinson's disease: long delays can improve
      performance.
AB  - A recent study in control subjects suggested the existence of separate pathways
      for oculomotor spatial working memory tasks depending on whether the delay before
      movement execution is either short or long (>20 s). The long delay pathway might
      bypass brain areas commonly affected by Parkinson's disease (PD). This study
      aimed to assess spatial working memory in Parkinson's disease using short (3 s)
      and long (30 s) delays in a memory-guided saccade task. Fifteen mild-moderately
      affected PD subjects off-medication, and 15 age and sex-matched controls were
      tested (PD mean age 65.3; control 65.9). Subjects were tested in a darkened room
      using a horizontal LED bar to generate eye movements which were recorded using an
      infrared limbus tracker. Percentage error in amplitude of the primary saccade was
      analysed by repeated measures ANOVA. There was a significant interaction between
      the groups and their response to the short and long delay periods (P<0.02). PD
      subjects were more strongly impaired in the short delay than the long delay
      trials when compared with controls. Analysis of the percentage error in amplitude
      of the final eye position showed the same pattern but only in female subjects.
      This study provides the first evidence that the proposed parallel spatial memory
      pathway utilised in longer delay periods is relatively unimpaired in PD. In a
      broader sense, our results suggest there might be other alternative pathways to
      overcome deficits in functions impaired by PD.

PMID- 15502985
TI  - The importance of perceived relative motion in the control of posture.
AB  - Two experiments investigated the role of optic flow in controlling posture. Both
      experiments measured postural sway in two virtual environments with different 3-D
      structure but the same optic flow. Observers attempted to maintain balance on one
      foot while viewing an object that appeared either rigid with respect to the
      environment or that appeared to move concomitantly with head movements. The
      apparent object motion concomitant with head motion was achieved by changing the
      perceived, but not physical, depth of the object. For both objects, the optic
      flow information was the same and only depth information was varied. Observers
      showed a decrease in stability (as measured by head sway) when viewing the object
      that appeared to move, suggesting that perceived relative motion, not optic flow,
      signals self-motion to the postural control system.

PMID- 15502986
TI  - Non-linear eye movements during visual-vestibular interaction under body
      oscillation with step-mode lateral linear acceleration.
AB  - We investigated visual-vestibular interactions in normal humans, where a constant
      speed of optokinetic stimulation was combined with whole body oscillation of
      lateral linear acceleration (10 m stroke). The acceleration mode was not
      sinusoidal, but rectangular (step). The pure optokinetic reflex (reference OKR)
      and the OKR under combined stimulation (combined OKR) were induced by a random
      dot pattern projected onto a hemispherical dome-screen affixed to a chair on a
      linear accelerator. The translational vestibulo-ocular reflex (tVOR) was
      determined separately in the dark during acceleration-step oscillation. Since the
      tVOR was masked by the OKR under combined stimulation, the interaction was
      assessed as changes in combined-OKR velocity at two segments of opposing
      acceleration; in other words, tVOR directions identical to (agonistic) and
      opposite to (antagonistic) the OKR direction. When a moderate optokinetic
      stimulus-speed of 40 deg/s was combined with a moderate acceleration of 0.3 G
      (3.0 m/s2) as in Experiment 1 (N=10), the combined-OKR velocity always increased
      during the agonistic condition, and the motion of the visual pattern was
      perceived as slow and clear in this segment. On the other hand, during the
      antagonistic condition, the combined-OKR velocity either remained unchanged or
      increased moderately, and the motion of the visual pattern was sensed as fast and
      unclear. Notably, in most subjects, the velocity difference in combined-OKR
      between the agonistic and antagonistic conditions was around the value of the
      tVOR velocity. In five of the ten subjects who completed an additional test
      session with the acceleration level increased from 0.3 to 0.5 G (4.9 m/s2),
      similar findings were maintained individually, suggesting independent behavior of
      tVOR. Therefore, we hypothesized that the interaction could be direction
      selective; in other words, both tVOR and OKR are additive during the agonistic
      condition, but tVOR is suppressed during the antagonistic condition. To extend
      this hypothesis further, another group of subjects was exposed to three different
      optokinetic-stimulus speeds of 20, 40 and 60 deg/s combined with an acceleration
      of 0.3 G (Experiment 2, N=15). Combined stimulation tended to optimize the
      combined-OKR velocity around the given optokinetic stimulus-speed, especially in
      those cases where the reference-OKR velocity deviated significantly from the
      stimulus speed. Changes in combined-OKR velocity were small at 20 deg/s, and were
      likely to be linear across the agonistic and antagonistic conditions. With
      increasing optokinetic stimulus-speeds, the direction-selective asymmetry
      hypothesized above was maintained in more than half of the subjects, while in the
      other subjects the combined-OKR velocity difference increased remarkably,
      probably due to an enhancement of the OKR gain. We conclude that tVOR suppression
      during the antagonistic stimulus-condition and non-linearity in the tVOR-OKR
      interaction are characteristic of the otolith system, even under moderate
      stimulus environments, in contrast to the linear eye-movement interaction in the
      semicircular canal system.

PMID- 15502987
TI  - Correlation between the durations of refractory period and intrinsic optical
      signal of retinal spreading depression during temperature variations.
AB  - Spreading depression (SD) is a neurophysiological phenomenon which occurs in the
      grey substance of the central nervous system. SD is characterised by a wave-like
      spread of depressed neuronal activity, by large ion shifts between intra- and
      extracellular space, by cellular depolarization, and by altered optical
      properties of the tissue giving rise to an intrinsic optical signal (IOS). In the
      shadow of SD further waves are difficult to trigger and such waves spread at
      lower velocity than usual. In this paper we examine the temperature dependence of
      the duration of this recovery (refractory) period and the temperature dependence
      of the duration of the IOS in the chicken retina. It is shown that these SD
      accompanying events are strongly dependent on temperature and that they are
      likely to depend on the metabolic rate in the tissue. The observed correlation of
      the duration of the IOS with the duration of the refractory period suggests that
      the IOS is a good indicator for the duration of the tissue recovery. Such a
      correlation would be of great value to the experimentalist who must know about
      the duration of the refractory period: while the latter is laborious to
      determine, recording the IOS is convenient.

PMID- 15502988
TI  - Modulations of input-output properties of corticospinal tract neurons by
      repetitive dynamic index finger abductions.
AB  - The goal of this study was to investigate how corticospinal tract neurons (CTNs)
      are modulated after repetitive dynamic muscle contractions. To address this
      question, changes of motor evoked potentials (MEPs) to transcranial magnetic
      stimulation and background EMG (B.EMG) activities were examined. Subjects were
      instructed to perform an isometric dynamic index finger abduction as accurately
      as possible under the target-force-matching tasks (10% or 30% MVC), while MEPs of
      a first dorsal interosseous (FDI) were elicited during performance of the task.
      After repetitive dynamic FDI contractions (100 trials), the following remarkable
      phenomena were observed: (1) both B.EMG activities and MEP amplitudes decreased
      in proportion to the number of trials, (2) these phenomena were most commonly
      observed in different conditions, i.e., different force levels and hands
      (preferred or non-preferred hands), and (3) after repetition of the tasks, the
      MEP amplitude/B.EMG (MEP/B.EMG) ratio became smaller. Decreases of B.EMG
      activities with reduction of MEP amplitudes and diminishing MEP/B.EMG ratio might
      suggest the occurrence of reorganization of input-output properties in CTNs for
      an efficient performance as a function of motor adaptation. Thus, we conclude
      that motor adaptation after repetitive dynamic muscle contractions probably
      occurs less specifically and due to susceptible modulations of spinal motoneurons
      reflected in the integrative functions of CTNs.

PMID- 15502989
TI  - Effects of bilateral subthalamic stimulation on gait kinematics and kinetics in
      Parkinson's disease.
AB  - Subthalamic nucleus (STN) stimulation, a recent surgical approach to Parkinson's
      disease (PD), has been shown to be effective in relieving motor symptoms. The
      present study carried out a full body gait analysis, during overground walking,
      on ten PD patients with bilaterally implanted STN stimulation devices. Walking
      performance was analyzed on the same day, in four conditions (Stim Off-Med Off,
      Stim On-Med Off, Stim Off-Med On, Stim On-Med On). The results showed that, on
      average, STN stimulation alone (S+M-) and L-dopa alone (S-M+), significantly
      increased gait speed, stride length and the lower limb joint Range of Motion
      (ROM) with respect to the basal condition (S-M-); also cadence was found to play
      a role in velocity increase, particularly when L-dopa was administered. Both
      treatments improved pelvis and trunk kinematics, and power production at the
      ankle and hip joints. The combination of the two treatments (S+M+) produced an
      additional effect on gait speed, stride length, ROM of knee and ankle joints,
      pelvis obliquity and trunk inclination. Given the additive and synergistic
      effects, it can be hypothesized that the two treatments have different mechanisms
      of action. Our results confirm the findings of earlier studies that employed
      treadmill walking.

PMID- 15502990
TI  - Touch responses made to remembered and visual target locations in the dark: a
      human psychophysical study.
AB  - Saccadic eye movements made to remembered locations in the dark show a distinct
      up-shift in macaque monkey, and slight upward bias in humans (Gnadt et al. 1991).
      This upward bias created in the visual spatial mapping of a saccade may be
      translated downstream in a hand/touch movement. This error could possibly reveal
      (a) information about the frames of reference used in each scenario and (b) the
      sources of this error within the brain. This would suggest an early planning
      stage if they are shared, or a later stage if the errors are distinct. METHODS:
      Eight human subjects performed touch responses to a touch screen monitor to both
      visual and remembered target locations. The subjects used a high-resolution touch
      screen monitor, a bite bar and chin-rest for restricting head movements during
      responses. All target locations were 20 degrees vectors from the central starting
      position in horizontal, vertical and oblique planes of motion. RESULTS: Subjects
      were accurate to both visual and remembered target locations with little
      variance. Subject means showed no significant differences between control and
      memory trials; however, a distinct asymmetry was observed between cardinal and
      oblique planes during memory trials. Subjects consistently made errors to oblique
      locations during touches made to the remembered location that was not evident in
      control conditions. This error pattern revealed a strong hypermetric tendency for
      oblique planes of touches made to a remembered location.

PMID- 15502992
TI  - Apomorphine-susceptible rats and apomorphine-unsusceptible rats differ in the
      tyrosine hydroxylase-immunoreactive network in the nucleus accumbens core and
      shell.
AB  - Individual variability in behavioural responses to stressors such as novelty and
      drugs of abuse is a well-known phenomenon in both animals and man. These
      individual differences are largely associated with differences in dopamine
      transmission in mesolimbic areas such as the nucleus accumbens. Apomorphine
      susceptible (APO-SUS) rats and apomorphine-unsusceptible (APO-UNSUS) rats serve
      as a valid animal model for individual differences and these two types of rat
      differ in a number of behavioural, physiological, endocrinological and
      pharmacological parameters. In order to study the differences in the
      catecholaminergic network in the nucleus accumbens, possibly underlying at least
      some of the differences between the two types of rat, we quantified the extent of
      the tyrosine-hydroxylase immunoreactive (TH-IR) network and the number of TH-IR
      varicosities in subareas of the nucleus accumbens core and shell in naive rats.
      This study shows that the nucleus accumbens of APO-SUS rats has a more extensive
      fibre network and more varicosities than the nucleus accumbens of APO-UNSUS rats,
      and that the subarea of the shell contains more varicosities than the subarea of
      the core. These data provide a basis for further studying the structural and
      neurochemical properties of the nucleus accumbens contributing to individual
      differences in response to stressors such as novelty and drugs of abuse.

PMID- 15502991
TI  - Spatial distribution of inhibitory synaptic connections during development of
      ferret primary visual cortex.
AB  - Intracortical inhibition in the primary visual cortex plays an important role in
      creating properties like orientation and direction selectivity. However, the
      development of the spatial pattern of inhibitory connections is largely
      unexplored. This was investigated in the present study. Tangential slices of
      layers 2/3 of ferret striate cortex were prepared for whole-cell patch clamp
      recordings, and presynaptic inhibitory inputs to pyramidal neurons were scanned
      by local photolysis of Nmoc-caged glutamate. Inhibitory synaptic currents (IPSCs)
      were first detected around postnatal day (P) 17. They originated locally around
      the recorded cells. Both the number and the total areas supplying the inhibitory
      inputs increased thereafter and peaked at the time around and shortly after eye
      opening (P29-37). A refinement period then followed in which the areas providing
      the majority of inhibitory inputs shrank from 600 microm around the recorded
      neurons to 200-300 microm in more mature animals (>/=P38). The amplitude of IPSCs
      increased progressively with increasing age. Long-range inhibitory inputs (>600
      microm) were present around eye opening and they often developed into a clustered
      patchy pattern in more mature animals (>/=P38). In summary, our results show a
      refinement and clustering in the spatial pattern of inhibitory connections during
      postnatal development of ferret visual cortex.

PMID- 15502993
TI  - Facilitation of cortically evoked potentials with motor imagery during post
      exercise depression of corticospinal excitability.
AB  - This study examined whether muscle fatigue alters the facilitatory effect of
      motor imagery on corticospinal excitability. We aimed to determine if post
      exercise depression of potentials evoked magnetically from the motor cortex is
      associated with alterations in internally generated movement plans. In experiment
      1, motor-evoked potentials (MEPs) were recorded from two right hand and two right
      forearm muscles, at rest and during motor imagery of a maximal handgrip
      contraction, in eight neurologically normal subjects, before and after a 2-min
      maximal voluntary handgrip contraction. Resting MEP amplitude was facilitated by
      motor imagery in three of the four muscles, but consistently only in two. Motor
      imagery also reduced the trial-to-trial variability of resting MEPs. Following
      the exercise, resting MEP amplitude was depressed reliably in only one muscle
      engaged in the task, although two other muscles exhibited some depression. Motor
      imagery MEPs were smaller after exercise, but the degree of facilitation compared
      to the rest MEP was unchanged. In experiment 2, TMS intensity was increased after
      exercise-induced MEP depression so that the MEP amplitude matched the pre
      exercise baseline. The amplitude of the MEP facilitated with motor imagery was
      not altered by MEP depression, nor was it increased when the TMS intensity was
      increased. These results suggest, at least with a simple motor task, that while
      post-exercise depression reduces corticospinal excitability, it does not appear
      to significantly affect the strength of the input to the motor cortex from those
      areas of the brain responsible for the storage and generation of internal
      representations of movement.

PMID- 15502994
TI  - Medical speciality and pattern of medicines prescription.
AB  - OBJECTIVE: To describe the prescribing patterns and their quality in relation to
      the prescriber's medical specialty in a defined population. METHODS: The study
      was done on a random sample of all primary care medical prescriptions made
      through the social security system during 1 year in Andorra, a small European
      country. Number and type of prescribed medicines, prescribers' medical speciality
      and patients' age and gender were recorded. Medical specialties considered were
      General Practice, Paediatrics, Cardiology, Pneumology, Gynaecology, Ophthalmology
      and Other. A set of various quality indicators [World Health Organisation
      (WHO)/International Network for Rational Use of Drugs (INRUD) indicators and
      others] was used. RESULTS: The number of medicines prescribed per encounter
      varied depending on the prescriber's medical specialty and patient's age.
      Cardiologists and pneumologists tended to prescribe more medicines than other
      medical specialties. Patients older than 65 years received more prescriptions
      than younger adults, mostly at the expense of cardiovascular drugs. The
      contribution of the various groups and subgroups of medicines and the scores of
      various prescribing indicators showed wide variability across the medical
      specialties. CONCLUSION: Prescribing patterns and indicators of prescription
      quality show wide variability depending on the prescriber's medical specialty.
      This has important implications for priority setting in information, continuous
      education and research.

PMID- 15502995
TI  - Does the early adopter of drugs exist? A population-based study of general
      practitioners' prescribing of new drugs.
AB  - OBJECTIVE: To analyse associations between indicators for adoption of new drugs
      and to test the hypothesis that physicians' early adoption of new drugs is a
      personal trait independent of drug groups. METHODS: In a population-based cohort
      study using register data, we analysed the prescribing of new drugs by Danish
      general practitioners. Angiotensin-II antagonists, triptans, selective cyclo
      oxygenase-2 antagonists and esomeprazol were used in the assessment. As
      indicators of new drug uptake, we used adoption time, cumulative incidence,
      preference proportion, incidence rate and prescription cost and volume. For each
      measure, we ranked the general practices. Ranks were pair-wise plotted, and
      Pearson's correlation coefficient ( r) was calculated. Next, we analysed the
      correlation between ranks across different drug classes. RESULTS: For all
      indicators, the general practitioners' adoption of one group of drugs was poorly
      associated with adoption of others ( r</=0.49), indicating that early adoption of
      one type of drugs is not associated with early adoption of another. For all drug
      groups, adoption time adjusted for practice size was only weakly associated with
      other indicators ( r: -0.56 to -0.27). Indicators, based on cost and volume of
      drugs, were highly correlated ( r: 0.96-0.99), and the others correlated
      reasonably well ( r: 0.51-0.91). CONCLUSIONS: Within drug groups, indicators of
      drug adoption, except for adoption time, correlate reasonably well. However, the
      theory that physicians' early adoption of new drugs is a personal trait
      independent of the type of drug could not be confirmed. The notion of the early
      drug-adopting general practitioner may be mistaken.

PMID- 15502997
TI  - Increasing the packing of small aneurysms with soft coils: an in vitro study.
AB  - The aim of this study was to determine whether or not the use of Soft and Ultra
      Soft Guglielmi detachable coils (GDCs) may improve the packing of cerebral
      aneurysms. Six coiling scenarios of a silicone aneurysm model were conducted
      using Standard, Soft, and Ultra Soft GDCs. Coils were introduced up to the point
      when the adjunct of one more coil caused protrusion out of the aneurysm sac.
      Packing ratios (volume of coils/aneurysm volume) ranged between 30 and 55%. The
      highest degree of packing was achieved with the combination of Soft GDC-18 coils
      and Ultra Soft GDC-10 coils. There is a positive relationship between the use of
      Soft and Ultra Soft GDC coils and greater aneurysm filling.

PMID- 15502996
TI  - Contrast-enhanced transcranial Doppler sonography in the follow-up of
      intracranial aneurysms after endovascular treatment.
AB  - Two pilot studies on a small number of patients demonstrated the feasibility of
      transcranial Doppler ultrasound evaluation in the follow-up of intracranial
      aneurysms treated with detachable coils. This prospective study aimed to assess
      the sensitivity of contrast-enhanced transcranial echo-Doppler in detecting
      partial aneurysmal occlusion following endovascular treatment. Transcranial
      Doppler sonography (TCD) with contrast administration and magnetic resonance
      angiography (MRA) or angiography were carried out after endovascular treatment in
      92 patients for 98 aneurysms of the anterior circulation. In 18% of cases, the
      quality of ultrasound exploration was deemed unsatisfactory for evaluation of the
      aneurysmal site. Results were concordant in 63% of patients (49/78). When
      occlusion appeared satisfactory at angiography or MRA, the result was concordant
      with TCD in 68% of cases (44/77). When a residual aneurysm was detected, TCD
      sensitivity was 38% (8/18). An analysis of subgroups failed to disclose anatomic
      or morphological aneurysm features in which transcranial echo-Doppler is
      sufficiently sensitive and specific to detect possible residual aneurysm or
      recanalisation. In our experience, even after contrast administration TCD is not
      sufficiently sensitive or specific in the detection of residual aneurysm to
      replace angiography or MRA.

PMID- 15502998
TI  - Three-dimensional rotation venography using the digital subtraction angiography
      unit with a flat-panel detector: usefulness for the transtemporal/transtentorial
      approaches.
AB  - We obtained the venograms using the two-dimensional digital subtraction
      angiography (2D DSA) images and three dimensional rotation venography (3D RV)
      images and investigated the potential usefulness of the 3D RV compared with
      venograms of 2D DSA using the newly developed three-dimensional rotation
      angiography unit with a flat-panel detector (FPD). This study included 26 sides
      (11 left, 15 right) in 20 cases (4 males and 16 females) who underwent
      radiographic examination for management of intracranial tumors and vascular
      diseases between May 2003 and December 2003. Each patient underwent diagnostic
      angiography performed on a DSA unit with a FPD. In all patients, the 2D DSA
      images, including anteroposterior view and lateral view of the carotid artery,
      were obtained in two stereoscopic views. The 3D RV was used to produce volume
      rendered images. Two neuroradiologists investigated the venous configuration of
      3D RV compared with that of 2D DSA about the relationship of the venous drainage
      system on the temporal lobe according to Guppy et al.'s classification. Twenty
      four sides of the 26 sides enabled the precious visualization on 3D RV images. In
      investigation of 2D DSA, 9 sides (37.5%) were classified into type A, 13 (54.2%)
      into type B, two (8.3%) into type C, and no sides into types D, E, and F. In
      investigation of 3D RV images, 10 sides (41.7%) were classified into type A, 9
      (37.5%) into type B, 1 (4.2%) into type C, 2 (8.3%) into type E, and 2 (8.3%)
      into type F. Seven of 24 sides demonstrated discrepancy in results between 2D DSA
      and 3D RV. The 3D RV could be performed by setting the adequate delay in between
      the injection of the contrast material and starting time of third rotation to
      acquire the opacified images. In Guppy et al.'s classification, the 3D RV images
      could demonstrate the precious venous drainage including the venous lakes with
      use of multiple views and variable reconstruction compared with 2D DSA. Our DSA
      system with FPD could provide good 3D RV images. These images are very useful for
      the skull-base surgery because we can understand the three-dimensional vascular
      anatomy preoperatively.

PMID- 15502999
TI  - Magnetic resonance angiography in the selection of patients suitable for
      neurosurgical intervention of ruptured intracranial aneurysms.
AB  - This study was aimed at establishing whether magnetic resonance angiography (MRA)
      can be applied to planning and performing surgery on ruptured intracranial
      aneurysms, especially in the early phase, without recourse to intra-arterial
      digital subtraction angiography (IA-DSA). From February 1998 to August 2001, in
      all patients presenting with a subarachnoid hemorrhage, MRA was performed first.
      A three-dimensional time-of-flight MRA protocol with T2-weighted coronal and
      axial images was used. If MRA demonstrated an aneurysm, surgery was undertaken.
      IA-DSA was limited to patients with negative or inconclusive MRA findings. We
      compared MRA images with operative findings in positive patients and with IA-DSA
      in negatives. IA-DSA was considered the gold standard when MRA findings were
      inconclusive. In this study, 205 consecutive patients (mean age 52.7 years, 69%
      women) were included. In 133 patients (64.9%) MRA demonstrated an aneurysm,
      directly followed by neurosurgical intervention. In 33 patients (16.1%) MRA
      findings were categorized as inconclusive. In 39 patients (19.0%) MRA results
      were negative. No false-negative ruptured aneurysms were selected by MRA. In only
      one patient surgical intervention was performed based on false-positive MRA
      findings. MRA can replace IA-DSA as a first diagnostic modality in the selection
      of patients suitable for surgical treatment of ruptured intracranial aneurysms.

PMID- 15503000
TI  - Serum p53 and bladder cancer: can serum p53 be used as a tumor marker?
AB  - The aim of this study was to find the correlation between serum p53 and carcinoma
      of the bladder and to investigate whether serum p53 protein can be used as a
      tumor marker for p53 gene alteration. The study included patients with carcinoma
      of the bladder and controls. Serum p53 protein estimation was done with an ELISA
      kit. There were 23 patients with superficial and 17 with invasive carcinoma. The
      median serum p53 was 31.5 U/ml in superficial and 41 U/ml in invasive cancer.
      This was significantly higher than the mean value (16.4 U/ml) of controls. Serum
      p53 rises in patients with carcinoma of the bladder and correlates with the grade
      of the disease . It can therefore be used as a tumor marker for bladder cancer.

PMID- 15503001
TI  - Gubernacular fibroblasts express the androgen receptor during testis descent in
      cryptorchid rats treated with human chorionic gonadotrophin.
AB  - Cryptorchidism was provoked in 3 day old rats treated with 17-beta-estradiol over
      30 days to identify the cells that express the androgen receptor (AR) during
      experimental testis descent in the gubernaculum. In one group of animals, testis
      descent was induced with human chorionic gonadotrophin (hCG) applied daily for 5
      or 10 days. A correlative study using a testosterone radioimmunoassay with
      electron microscopy and immunocytochemical detection of AR was performed in
      gubernacula of hCG treated and untreated control animals. The gubernaculum of
      rats undergoing testes descent showed a dramatic increase in the number of AR
      positive cells. These were located in the connective tissue among smooth muscle
      cells in the gubernacular cord and between striated muscle fibers in the bulb. In
      both regions, the AR-positive cells were identified as fibroblasts. Several
      clusters of amorphous material appeared in the extracellular matrix of the
      connective tissue in hCG treated rats. Our results suggest that testosterone
      induces the expression of AR in gubernacular fibroblasts which seem to degrade
      the extracellular matrix during gubernacular involution.

PMID- 15503002
TI  - Small-bowel intussusception around a gastrojejunostomy tube resulting in ischemic
      necrosis of the intestine.
AB  - Gastrojejunostomy (GJ) tube feeding has made a significant difference in the
      lives of children with oropharyngeal motor problems and severe gastroesophageal
      reflux disease. It may, however, also lead to small-bowel intussusception.
      Previously, these intussusceptions have been reported as intermittent, self
      limiting, and innocuous. We report a case of a GJ-tube-related small-bowel
      intussusception that resulted in ischemic necrosis of the bowel. This case
      suggests that close monitoring and confirmation of successful reduction is
      necessary in the treatment of GJ-tube-related small-bowel intussusception.

PMID- 15503003
TI  - Clinical and sonographic criteria of acute scrotum in children: a retrospective
      study of 172 boys.
AB  - BACKGROUND: Diagnosis of testicular torsion in children is challenging, as
      clinical presentation and findings may overlap with other diagnoses. OBJECTIVE:
      To define the clinical and ultrasound criteria that best predict testicular
      torsion. MATERIALS AND METHODS: The records of children hospitalized for acute
      scrotum from 1997 to 2002 were reviewed. The clinical and ultrasound findings of
      children who had a final diagnosis of testicular torsion were compared with those
      of children who had other diagnoses (torsion of the testicular appendix,
      epididymitis, and epididymo-orchitis). RESULTS: Forty-one children had testicular
      torsion; 131 had other diagnoses. Stepwise regression analysis yielded three
      factors that were significantly associated with testicular torsion: duration of
      pain < or =6 h; absent or decreased cremasteric reflex; and diffuse testicular
      tenderness. When the children were scored by final diagnosis for the presence of
      these factors (0-3), none of the children with a score of 0 had testicular
      torsion, whereas 87% with a score of 3 did. The ultrasound finding of decreased
      or absent testicular flow had a sensitivity of 63% and a specificity of 99%.
      Eight of ten children with testicular torsion and normal or increased testicular
      flow had a coiled spermatic cord on ultrasound. CONCLUSION: We suggest that all
      children with acute scrotal pain and a clinical score of 3 should undergo
      testicular exploration, and children with a lower probability of testicular
      torsion (score 1 or 2) should first undergo diagnostic ultrasound. Because the
      presence of testicular flow does not exclude torsion, the spermatic cord should
      be meticulously evaluated in all children with acute scrotum and normal or
      increased testicular blood flow.

PMID- 15503004
TI  - www.PedRad.info, the first bilingual case-oriented publication platform for
      pediatric radiology.
AB  - On the Internet, there are few pediatric radiology databases. The most important
      and complete Web site is PediatricRadiology.com, which provides many radiological
      links but does not have its own database. We present an Internet project called
      PedRad.info (also known as Kinderradiologie-Online). The open-source, case
      oriented publication platform publishes validated pediatric radiology findings on
      the Internet. A comparable on-line program, even for adult radiology, does not
      exist, so this tool is a pioneer in the area of Web-based information technology
      for medical and radiological communities.

PMID- 15503005
TI  - MED, COMP, multilayered and NEIN: an overview of multiple epiphyseal dysplasia.
AB  - This overview covers the group of disorders that presents radiographically as
      multiple epiphyseal dysplasia (MED). The disorders include "classic MED" (Ribbing
      and Fairbank types): MED that is caused by mutations in the cartilage oligomeric
      matrix protein (COMP), type IX collagen, and matrilin 3 genes (MATN3); and MED
      with multilayered patella, brachydactyly, and clubbed feet resultant from
      mutations in gene defect diastrophic dysplasia (DTDST). The recently identified
      gene/molecular abnormalities in these disorders have made more exact
      identification possible in many cases, although clinical testing is not always
      available. However, there are specific radiographic findings that allow the
      accurate diagnosis to be made, thus potentially guiding which molecular defect(s)
      should be investigated. The modes of inheritance of these distinct MED conditions
      are not identical. When a specific diagnosis is made, proper genetic counseling
      as well as prognostication, management issues and complications can be delineated
      to the patient and family. This review will include the mechanics of diagnostic
      and molecular triage for these disorders.

PMID- 15503006
TI  - Gadolinium-enhanced magnetic resonance angiography in neonates and infants
      suspected of caval or aortic thrombosis.
AB  - BACKGROUND: Gadolinium-enhanced magnetic resonance angiography (MRA)is a well
      established technique in older children and adults. No studies have focused on
      its use in neonates and small infants. OBJECTIVE: Our objective was to study the
      use of gadolinium-enhanced MRA in neonates and infants suspected of caval or
      aortic thrombosis. MATERIALS AND METHODS: Gadolinium-enhanced MR angiography was
      performed on seven neonates and small infants for the evaluation of caval or
      aortic thrombosis. Gadolinium-DTPA at a dose of 0.3 mmol/kg (minimum dose 1 ml)
      was injected using a power injector (0.2 ml/s). Contrast-enhanced MRA was
      performed using a 3-D, fast, radiofrequency spoiled gradient-echo sequence
      (TR/TE: 4.8/1.1, flip angle 45 degrees , matrix 256 x 128, slice thickness 2.6 mm
      interpolated to 1.3 mm, FOV variable, NEX=1.0). RESULTS: Diagnostic-quality
      angiograms were obtained in all seven neonates. Superior vena cava thrombosis was
      identified in two neonates, and abdominal aortic thrombosis was present in one
      neonate. CONCLUSION: It is practical to perform gadolinium-enhanced MRA in
      neonates weighing as little as 600 g for the detection of caval or aortic
      thrombosis.

PMID- 15503007
TI  - Hyper IgE in New Zealand black mice due to a dominant-negative CD23 mutation.
AB  - Immunoglobulin E (IgE) plays a critical role in both resistance to parasitic
      infection and allergy to environmental antigens. The IgE response is in turn
      regulated by the B-cell co-receptor CD23, and CD23-deficient mice show
      exaggerated IgE responses and airway hyper-responsiveness. In this report, we
      show that New Zealand black (NZB) mice express a variant CD23 allele, with
      mutations in both the C-lectin-binding domain and stalk region, which fails to
      bind IgE at high affinity and has reduced expression on the cell surface.
      Expression of the variant CD23 chain interferes with trimerisation of the
      receptor and has a dominant-negative effect leading to reduced IgE binding in
      crosses between NZB and other strains. Genetic mapping shows that the variant
      CD23 leads to an exaggerated primary IgE response, which is independent of other
      strain-specific effects. These results suggest that NZB mice or mice carrying the
      variant allele will be useful models for studying both allergy and quantitative
      traits associated with atopy. The exaggerated IgE response provides an
      explanation for the natural resistance of NZB mice to parasitic infection by
      Leishmania.

PMID- 15503008
TI  - Characterization of a highly inducible novel CC chemokine from differentiated
      rainbow trout (Oncorhynchus mykiss) macrophages.
AB  - A full-length cDNA clone encoding a novel trout CC chemokine was identified in
      expressed sequence tags generated from lipopolysaccharide (LPS)-stimulated in
      vitro differentiated macrophages isolated from the head kidney of the rainbow
      trout (Oncorhynchus mykiss). The putative 101-amino-acid protein is 38% similar
      to Macaca mulatta CCL4 (macrophage inflammatory protein 1beta) but is also
      similar to several other related mammalian CC chemokines, including human Act-2.
      Real-time PCR and conventional RT-PCR revealed significant up-regulation of
      transcript levels of the trout CCL4-like mRNA in LPS-stimulated in vitro
      differentiated macrophages. In unstimulated trout, CCL4-like mRNA expression was
      detected at different levels in all tissues tested, whereas in LPS-challenged
      animals (6 mg/kg), CCL4-like mRNA increased in intestine, ovary and spleen at
      both 24 h and 72 h post-injection. In gills, CCL4-like mRNA expression was
      inhibited after LPS administration. Based on the highly regulated expression
      pattern exhibited by the trout CCL4-like mRNA, it is likely that this chemokine
      plays an important regulatory role in the immune response of trout.

PMID- 15503009
TI  - Expression of the Fusarium oxysporum lactonase gene in Aspergillus oryzae:
      molecular properties of the recombinant enzyme and its application.
AB  - The lactonase gene of Fusarium oxysporum was expressed in Aspergillus oryzae for
      optical resolution of DL-pantoyl lactone. When the chromosomal gene encoding the
      full-length form of the lactonase, which has its own NH2-terminal signal peptide,
      was introduced in the host cells, the resulting transformant produced an enzyme
      of 46,600 Da, which corresponded to the wild-type enzyme. In contrast, A. oryzae
      transformed with the cDNA coding the mature enzyme produced a protein of 41,300
      Da. Deglycosylation analysis with an endoglycosidase revealed that the difference
      in molecular mass arose from the different sugar contents of the recombinant
      enzymes. The mycelia of the transformant were used as a catalyst for asymmetric
      hydrolysis of DL-pantoyl lactone. The initial velocity of the asymmetric
      hydrolysis reaction catalyzed by the transformant was estimated to be 30 times
      higher than that by F. oxysporum. When the mycelia of the transformant were
      incubated with a 20% DL-pantoyl lactone solution for 4 h, 49.9% of the racemic
      mixture was converted to D-pantoic acid (>95% ee).

PMID- 15503010
TI  - Focal osteolysis in total hip replacement: CT findings.
AB  - OBJECTIVE: To describe the CT findings of focal osteolysis following total hip
      replacement (THR). DESIGN AND PATIENTS: CT imaging features of 30 THRs with focal
      osteolysis visualized on follow-up radiographs and undertaken revision surgery
      were reviewed. On CT scans, the shape and anatomic location of osteolytic lesions
      was recorded, as well as their size and number. The presence of cortical
      disruption or expansion, liner wear, metallosis, and heterotopic ossification was
      also noted. In each case, surgical and histologic findings were correlated with
      imaging features. RESULTS: Focal osteolysis was common in the superior part of
      acetabular and femoral components. CT features of focal osteolysis were multiple,
      expansile, oval, or round radiolucencies, which were conglomerated into
      multilobular shape. The cortex adjacent to the osteolytic lesions revealed
      irregular thinning and discontinuity (29/30, 97%) accompanied by a few tiny
      fragments. Liner wear was common (27/30, 90%), and metallosis was frequent (8/30,
      26.7%). Pathologic results were foreign body reaction in 20 patients, chronic
      inflammation in eight, and fibrosis in two. CONCLUSION: CT appearances of focal
      osteolysis following THR are multilobulated lucent areas with expansile
      periosteal reaction and cortical abnormalities, mimicking infection or tumor. We
      consider that CT is useful for the prediction and assessment of the nature and
      extent of focal osteolysis.

PMID- 15503012
TI  - Symptomatic giant (10-cm) bone island of the tibia.
AB  - A bone island represents a focus of mature compact bone within the cancellous
      bone, and it can be diagnosed based on characteristic clinical and radiologic
      features. The lesion is typically asymptomatic with a preference for the pelvis,
      femur, and other long bones. On radiographs, the lesion appears as an ovoid,
      round or oblong homogeneously dense and sclerotic focus in the cancellous bone.
      The characteristic features of this lesion are radiating bony streaks, known as
      thorny radiations or pseudopodia. Most bone islands are small, and the majority
      of these lesions measure from 0.1 to 2.0 cm. A giant bone island, defined as
      having a diameter greater than 2 cm, has been rarely reported in the English
      language literature. We report here on a case of a giant bone island that
      measured 10 x 1.7 x 1 cm in the diaphysis of the right tibia in a 31-year-old man
      who complained of right lower leg pain for 3 weeks.

PMID- 15503013
TI  - MRI demonstration of cervical spondylodiscitis and distal full-length bilateral
      paraspinal cold abscesses successfully treated by drug regimen only.
AB  - OBJECTIVE: Cold abscesses, although common in spinal tuberculosis, are usually
      localized to the level of infection, follow tissue planes, and may extend into
      the spinal canal at any level. They may cause symptoms resulting from
      neurovascular compression, hemorrhage, and direct mass effect. DESIGN AND
      PATIENTS: We present an unusual case of cervical tuberculous spondylodiscitis in
      a 25-year old man with a cold abscesses involving the retropharyngeal,
      mediastinal, and retroperitoneal areas bilaterally. The abscess tracked from the
      neck to the psoas muscles bilaterally. Following the diagnosis the patient
      received 9 months of antituberculous therapy. RESULTS: MRI showed resolution on
      medical treatment alone. CONCLUSIONS: Even in the presence of massive
      paravertebral cold abscesses medical treatment alone may well suffice for this
      common worldwide disorder. MRI is ideal for monitoring regression of massive
      abscesses in deep anatomical locations.

PMID- 15503017
TI  - Hereditary spherocytosis uncovered in adulthood due to concomitant lead
      poisoning.

PMID- 15503018
TI  - Mesenteric venous thrombosis in a patient with congenital afibrinogenemia and
      diffuse peritonitis.

PMID- 15503019
TI  - Distribution of the C282Y and H63D polymorphisms in hereditary hemochromatosis
      patients from the French Basque Country.
AB  - The distribution of HFE mutations was studied in patients from the French Basque
      Country with hereditary hemochromatosis (HH). The C282Y mutation was
      underrepresented but H63D seemed to demonstrate the highest prevalence when
      compared with other European countries. In addition, symptomatic HH was rarer in
      autochthonous Basques. This profile is interesting to consider in view of
      population genetics and should be associated with the search for non-HFE
      mutations.

PMID- 15503020
TI  - Life-threatening cryoglobulinemia in HCV-negative Southern Chinese and a novel
      association with structural aortic abnormalities.
AB  - Cryoglobulinemia is uncommon in Southern Chinese in Hong Kong, with tropical
      climates and low incidence of hepatitis C virus (HCV) infection. Eight positive
      cases were detected among 481 patients screened for cryoglobulins over a 10-year
      period. Three HCV carriers (38%) ran benign courses. The others included two
      carriers of hepatitis B virus (HBV), two patients with adenocarcinoma, and one
      with chronic lymphocytic lymphoma. Four of them (except one HBV carrier) ran
      fulminant courses and died of cryoglobulin-related complications. Interestingly,
      all four cases also had structural aortic abnormalities, including multiple
      dissections, aneurysms, and congenital aortic arch abnormalities, which were
      often life threatening. The association of aortic abnormality and
      cryoglobulinemia is hitherto unreported and may be peculiar to our ethnic group.
      Aggressive control of the cryoglobulin may help to reduce aortic intima damage.

PMID- 15503021
TI  - IgD multiple myeloma--a clinical profile and outcome with chemotherapy and
      autologous stem cell transplantation.
AB  - IgD myeloma accounts for 2% of myeloma subtypes and has higher incidence of
      complications and a poorer outcome. The characteristics and outcomes of 25
      patients with IgD myeloma (2.6% of all myeloma patients), including 11 patients
      treated with autologous stem cell transplantation (ASCT) are reported. The
      presenting features were not unique for myeloma, but it appears that the
      commonest presenting symptom was bone pain in 20 (80%) patients. Other associated
      disorders were B-CLL in -1 patient and hairy cell leukemia in another. Three
      patients had a marked increase in bone marrow reticulin. Three (out of a total of
      9) patients had 13q deletion (1 by cytogenetics and 2 by interphase fluorescence
      in situ hybridisation [FISH]), while 2 patients had a complex karyotype. A total
      of 11 patients were treated with ASCT, while 14 patients had chemotherapy alone.
      The response to treatment was: in the ASCT group 2 had a complete response (CR)
      and 9 had a good partial response (PR), while in the chemotherapy group 6 had a
      good PR with no CRs. The median overall survival (OS) and progression-free
      survival (PFS) after autologous peripheral blood stem cell transplantation
      (APBSCT) has not yet been reached after a median follow up of 4 years. The median
      PFS after chemotherapy was 1.23 years (95% CI 1.02-1.44). The mean OS
      transplantation was 5.09 years compared with 2.03 years for those treated with
      chemotherapy alone. However, this difference was not statistically significant
      (log rank p=0.09). This small series appears to suggest that outcome for IgD
      myeloma remains poor with chemotherapy and appears to be superior with ASCT, and
      larger studies are needed to confirm these findings.

PMID- 15503024
TI  - Enhanced antitumor activity of irofulven in combination with irinotecan in
      pediatric solid tumor xenograft models.
AB  - PURPOSE: Irofulven, a novel chemotherapeutic agent with a broad spectrum of
      activity, is effective against preclinical models of pediatric tumors. The
      cytotoxic activity of irofulven is augmented when combined with agents that
      interact with DNA topoisomerase I; however, none of the reported studies have
      used the protracted dosing schedule found to be active clinically in treatment of
      childhood cancers. The objective of this study was to evaluate the antitumor
      activity of irofulven in combination with irinotecan administered on a protracted
      schedule in a panel of pediatric solid tumor xenografts. METHODS: Irofulven and
      irinotecan were evaluated alone or in combination against eight independent
      xenografts, which included childhood brain tumors (n=5), neuroblastoma (n=1), and
      rhabdomyosarcoma (n=2). Irofulven was administered i.v. daily for 5 days with
      courses repeated every 21 days for a total of three cycles. Doses of irofulven
      ranged from 1.33 to 4.6 mg/kg. Irinotecan was given i.v. daily for 5 days each
      week for 2 weeks repeated every 21 days for three cycles at doses between 0.28
      and 1.25 mg/kg. RESULTS: Irofulven and irinotecan, given as single agents,
      induced few responses in pediatric solid tumor xenografts at the selected doses.
      At the same doses, irofulven in combination with irinotecan demonstrated superior
      antitumor activity, inducing complete responses in seven of the eight xenograft
      lines. CONCLUSIONS: These studies show that the cytotoxic activity of irofulven
      is greater when combined with protracted administration of irinotecan. Although
      the systemic exposure of irofulven required to induce objective responses in this
      panel of pediatric solid tumors was in excess of that achievable in patients
      receiving maximally tolerated doses using this schedule of drug administration,
      the enhanced activity of irofulven in combination with irinotecan supports the
      pursuit of alternative administration strategies and combinations.

PMID- 15503027
TI  - Population pharmacokinetic analysis of 17-(allylamino)-17-demethoxygeldanamycin
      (17AAG) in adult patients with advanced malignancies.
AB  - PURPOSE: 17-(Allylamino)-17-demethoxygeldanamycin (17AAG) is a novel anticancer
      agent in clinical development. The objectives of this study were to develop a
      population pharmacokinetic model for 17AAG and its major metabolite, 17AG, and to
      investigate influences of patient characteristics and biochemical markers on
      pharmacokinetic parameters estimated for 17AAG and 17AG. EXPERIMENTAL DESIGN: In
      a phase I clinical study, 17AAG was administered by intravenous infusion to 43
      patients with refractory, advanced malignancies. Plasma concentrations of 17AAG
      and 17AG were determined by high-performance liquid chromatography. Plasma
      concentration vs time data were modeled using NONMEM. Nine covariates (age, sex,
      performance status, weight, height, body surface area, AST, bilirubin and serum
      creatinine) were investigated for their influences on individual pharmacokinetic
      parameters. RESULTS: Plasma concentration vs time data were best described by a
      two-compartment model for 17AAG and a one-compartment model for 17AG. Volumes of
      distribution were 24.2 and 89.6 l for 17AAG. Total elimination clearances were
      26.7 and 21.3 l/h for 17AAG and 17AG, respectively. Both fixed and random effects
      pharmacokinetic parameters were well estimated. None of the covariates explained
      the interindividual variability in 17AAG and 17AG pharmacokinetic parameters or
      improved the fit of the model based on objective function changes. CONCLUSIONS: A
      population pharmacokinetic model was developed to describe 17AAG and 17AG
      population pharmacokinetic parameters and interindividual variabilities. There
      were substantial interindividual variabilities in 17AAG and 17AG pharmacokinetic
      parameters despite BSA-normalized dosing.

PMID- 15503029
TI  - A Sch9 protein kinase homologue controlling virulence independently of the cAMP
      pathway in Cryptococcus neoformans.
AB  - The polysaccharide capsule is one of the established virulence factors in
      Cryptococcus neoformans that provides a barrier against the host-mediated immune
      response. Mutation of the gene encoding the Saccharomyces cerevisiae Sch9 protein
      kinase homologue resulted in cells with enlarged capsules in C. neoformans.
      Capsule production was abrogated in sch9 pka1 double mutants, indicating that
      protein kinase A (PKA) signaling is still necessary for capsule formation in sch9
      mutants. The sch9 mutant also exhibited increased thermal tolerance, a phenotype
      similar to sch9 mutant strains of S. cerevisiae. In addition, the sch9 mutant was
      attenuated in mating and the highly encapsulated cells were attenuated in
      virulence, in contrast to the pkr1 mutant, lacking the regulatory subunit of
      protein kinase A, that produced similarly enlarged capsules yet was increased in
      virulence. Interestingly, the virulence for the sch9 mutant strain could be
      restored by introduction of a pkr1 mutation; and the sch9 pkr1 mutant strain was
      dramatically increased in size and capsule thickness, suggesting that Sch9 and
      PKA function via different targets involved in virulence. Our findings support a
      model in which Sch9 modulates capsule formation and contributes to the virulence
      of C. neoformans both independently of and in conjunction with the cAMP-PKA
      pathway.

PMID- 15503030
TI  - Phantom cytomegalovirus infection in vasculitis patients: what it means and what
      to do.
AB  - We report our experience and hypothesis on the diagnosis and treatment of
      patients with vasculitis who are simultaneously diagnosed with serum-positive
      cytomegalovirus (CMV) immunoglobulin (Ig)M antibodies and negative CMV DNA
      polymerase chain reaction (PCR). It remains unknown how to treat this kind of
      "phantom" CMV infection. In a patient diagnosed with Henoch-Schonlein vasculitis,
      CMV IgM titers were increased while angiitis and renal function deteriorated.
      Empiric treatment of phantom CMV infection with ganciclovir in this CMV IgM
      positive and PCR-negative patient resulted in complete vasculitis remission,
      serum CMV antibody seroconversion, and renal function improvement. These results
      imply something more than coincidence.

PMID- 15503031
TI  - Detection of microsatellite instability during somatic embryogenesis of oak
      (Quercus robur L.).
AB  - Five microsatellite loci (QpZAG1/5, QpZAG9, QpZAG36, MSQ4, MSQ13) were used to
      test for genetic stability of three somatic embryogenic culture lines of Quercus
      robur L. and plantlets derived therefrom. DNA variation was detected among
      somatic embryos within all embryogenic lines, whereas no genetic instability was
      found among the regenerated plants. Two microsatellite loci revealed variation,
      and a locus-dependent instability was observed. The most polymorphic and useful
      microsatellite locus for detecting genetic variation was QpZAG9, with 28.5% of
      the investigated loci being variable.

PMID- 15503032
TI  - A rapid and efficient transformation protocol for the grass Brachypodium
      distachyon.
AB  - A fast and efficient microprojectile bombardment-mediated transformation protocol
      is reported for the grass species Brachypodium distachyon, a proposed alternative
      model plant to Oryza sativa for functional genomics in grasses. Embryogenic calli
      derived from immature embryos were transformed by a construct containing the uidA
      (coding for beta-glucuronidase) and bar (coding for phosphinothricin acetyl
      transferase) genes, and bialaphos, a non-selective herbicide, was used as the
      selection agent throughout all phases of the tissue culture. Average
      transformation efficiencies of 5.3% were achieved, and for single bombardments
      transformation efficiencies of up to 14% were observed. The time frame from the
      bombardment of embryogenic callus to the harvesting of transgenic T1 seeds was 29
      weeks and 25 weeks for the diploid and two tetraploid accessions used,
      respectively. Since the seed-to-seed life cycle is 19 weeks for the diploid and
      15 weeks for the tetraploid accessions, our B. distachyon transformation system
      allows testing of both the T0 and the T1 generation as well as production of T2
      seeds within 1 year.

PMID- 15503033
TI  - Different effects on ACC oxidase gene silencing triggered by RNA interference in
      transgenic tomato.
AB  - RNA interference (RNAi) is a potent trigger for specific gene silencing of
      expression in a number of organisms and is an efficient way of shutting down gene
      expression. 1-Aminocyclopropane-1-carboxylate (ACC) oxidase catalyzes the
      oxidation of ACC to ethylene, a plant growth regulator that plays an important
      role in the tomato ripening process. In this research, to produce double-stranded
      (ds)RNA of tomato ACC oxidase, we linked the sense and antisense configurations
      of DNA fragments with 1,002-bp or 7-nt artificially synthesized fragments,
      respectively, and then placed these under the control of a modified cauliflower
      mosaic virus 35S promoter. The dsRNA expression unit was successfully introduced
      into tomato cultivar Hezuo 906 by Agrobacterium tumefaciens-mediated
      transformation. Molecular analysis of 183 transgenic plants revealed that the
      dsRNA unit was integrated into the tomato genome. With respect to the construct
      with the 1,002-bp linker, the severity of phenotypes indicated that 72.3% of the
      transformed plants had non-RNA interference, about 18.1% had semi-RNA
      interference, and only 9.6% had full-RNA interference. However when the construct
      with the 7-nt linker was used for transformation, the results were 13.0%, 18.0%,
      and 69.0%, respectively, indicating that the short linker was more efficient in
      RNAi of transgenic tomato plants. When we applied this fast way of shutting down
      the ACC oxidase gene, transgenic tomato plants were produced that had fruit which
      released traces of ethylene and had a prolonged shelf life of more than 120 days.
      The RNA and protein analyses indicated that there was non-RNA interference, semi
      RNA interference and full-RNA interference of ACC oxidase in the transgenic
      tomato plants.

PMID- 15503034
TI  - Induction of callus from a metal hypertolerant fern, Athyrium yokoscense, and
      evaluation of its cadmium tolerance and accumulation capacity.
AB  - The callus of a metal hypertolerant fern, Athyrium yokoscense, was induced from
      the spores generated on a small sectioned frond in vitro. The callus grew
      vigorously with the periodical medium change, especially in a liquid culture.
      When the callus and regenerated tissues were exposed to Cd, every tissue
      tolerated at least 1 mM Cd for >1 month. These tissues accumulated high levels of
      Cd (maximum 3.3 mg g(-1) dry weight in roots) in accordance with the Cd
      concentration of the medium, and the Cd concentrations of all parts, except
      roots, were at a similar level. The data suggest that the Cd tolerance of this
      fern is basically independent of the plant parts and the developmental stages,
      although the accumulation ability is higher in roots than in the other plant
      parts.

PMID- 15503035
TI  - Agrobacterium tumefaciens-mediated transformation of chickpea (Cicer arietinum
      L.): gene integration, expression and inheritance.
AB  - A reproducible method of Agrobacterium-mediated transformation was developed for
      Cicer arietinum (chickpea). Initial explants consisted of longitudinal slices
      from embryonic axes of imbibed, mature seed. The plasmid contained a bi
      functional fusion gene conferring both beta-glucuronidase and neomycin
      phosphotransferase activities, under the control of a 35S35SAMV promoter. Using a
      series of tissue culture media for co-cultivation, shoot initiation and rooting,
      we recovered transgenic plants from approximately 1.3% of the sliced embryo axes.
      The addition of a shoot elongation medium to the protocol improved the success
      rate to 3.1% but increased the time in tissue culture. Inheritance of the gus
      gene was followed through four generations, both through expression and Southern
      hybridization assays, and showed the expected Mendelian inheritance pattern.

PMID- 15503036
TI  - Thrombosed dialysis access grafts: randomized comparison of the Amplatz
      thrombectomy device and surgical thromboembolectomy.
AB  - We report the final results of the trial comparing the Amplatz thrombectomy
      device (ATD) with surgical thromboembolectomy (ST) to declot thrombosed dialysis
      access grafts (DAG). The study population consisted of 174 DAG, 109 of which were
      randomized to mechanical thrombectomy using the ATD and 65 of which were
      randomized to conventional surgical thromboembolectomy. Forty grafts were re
      enrolled in the trial when they failed beyond the 90 days follow-up after the
      initial treatment. Thirty-one were re-enrolled for mechanical thrombectomy and
      nine were re-enrolled for surgical thrombectomy, resulting in a total of 140 ATD
      procedures and 74 surgical thromboembolectomy. Immediate thrombectomy success was
      defined as greater than 90% thrombus removal followed by the ability to dialyze
      after treatment, and analysis of long term success based on graft patency at 30
      and 90 days, with successful dialysis. Immediate thrombectomy success with the
      ATD procedure was achieved in 79.2% and with ST in 73.4%. Patency of the graft,
      with successful dialysis, at 30 days with the ATD procedure was 79.2% and with ST
      was 73.4%. Patency of the graft, with successful dialysis, at 90 days with the
      ATD procedure was 75.2% and with ST was 67.8%. The data collected in this study
      provided a prospective comparison of mechanical thrombectomy with the ATD and ST
      performance in thrombosed DAG. The results of the performance of both methods
      were comparable. No statistically significant differences were seen.

PMID- 15503037
TI  - 3D time-of-flight MR angiography of the intracranial vessels: optimization of the
      technique with water excitation, parallel acquisition, eight-channel phased-array
      head coil and low-dose contrast administration.
AB  - The aim of this study is three folds: to compare the eight-channel phased-array
      and standard circularly polarized (CP) head coils in visualisation of the
      intracranial vessels, to compare the three-dimensional (3D) time-of-flight (TOF)
      MR angiography (MRA) techniques, and to define the effects of parallel imaging in
      3D TOF MRA. Fifteen healthy volunteers underwent 3D TOF MRA of the intracranial
      vessels using eight-channel phased-array and CP standard head coils. The
      following MRA techniques were obtained on each volunteer: (1) conventional 3D TOF
      MRA with magnetization transfer; (2) 3D TOF MRA with water excitation for
      background suppression; and (3) low-dose (0.5 ml) gadolinium-enhanced 3D TOF MRA
      with water excitation. Results are demonstrating that water excitation is a
      valuable background suppression technique, especially when applied with an eight
      channel phased-array head coil. For central and proximal portions of the
      intracranial arteries, unenhanced TOF MRA with water excitation was the best
      technique. Low-dose contrast enhanced TOF MRA using an eight-channel phased-array
      head coil is superior in the evaluation of distal branches over the standard CP
      head coil. Parallel imaging with an acceleration factor of two allows an
      important time gain without a significant decrease in vessel evaluation. Water
      excitation allows better background suppression, especially around the orbits and
      at the periphery, when compared to conventional acquisitions.

PMID- 15503040
TI  - Sonographic findings in stress fractures of the lower limb: preliminary findings.
AB  - Stress fractures are common injuries frequently overlooked on first radiographs,
      especially in the early course. The gold standard for accurate diagnosis is MRI
      and scintigraphy. We report six cases of stress fractures of the lower limb
      diagnosed with sonography and describe typical sonographic features.

PMID- 15503038
TI  - Early modifications of hepatic perfusion measured by functional CT in a rat model
      of hepatocellular carcinoma using a blood pool contrast agent.
AB  - Macromolecular contrast-enhanced functional CT was performed to characterize
      early perfusion changes in hepatocellular carcinoma (HCC). Fourteen rats with
      chemically induced primary liver tumors ranging pathologically from hyperplasia
      to HCC and 15 control rats were investigated. Two dynamic CT scans using an
      experimental macromolecular contrast agent were performed on a single slice 11
      and 18 weeks after tumor induction followed by pathological examination. A
      deconvolution mathematical model was applied, yielding the hepatic perfusion
      index (HPI), mean transit time (MTT), liver distribution volume (LDV) and
      arterial, portal and total blood flows (FA, FP, FT). Analysis was performed on
      one slice per rat, containing overall two hyperplasia, six dysplasia and 15 HCC.
      On the first scans, HCC at an early pathological stage had a low FP (-30%,
      P=0.002) but a normal arterial-portal balance. On the scan contemporary to
      pathology, HCC perfusion parameters showed an inversion of the arterial-portal
      balance (HPI +212%, P<0.0001), with a high FA (+56%, P=0.002) and a low FP (-69%,
      P<0.0001). Sensitivity and specificity of detection of HCC by perfusion CT were
      high (87 and 80%) on late scans; but also on the earlier scans (86 and 65%), even
      though only one (7%) was visible to the eye. Perfusion-CT allowed early detection
      of HCC. This technique could contribute in the detection and characterization of
      liver lesions in clinical studies.

PMID- 15503041
TI  - Redistribution of cerebropetal blood flow in patients with carotid artery
      stenosis measured non-invasively with fast cine phase contrast MR angiography.
AB  - The purpose was to evaluate the blood flow redistribution in the neck vessels of
      patients with internal carotid artery (ICA) stenosis. Eighty-six patients with
      ICA stenosis underwent contrast-enhanced magnetic resonance angiography (CEMRA)
      and fast 2D phase contrast (2D-PC) sequence to measure the mean blood flow (MBF)
      of ICA, basilar artery (BA) and middle cerebral artery (MCA). CEMRA revealed 53
      severe stenoses, 45 moderate stenoses and 3 occluded vessels. Patients with a
      unilateral severe ICA stenosis had a significantly reduced MBF of the ICA
      compared to the control group; the MBF reduction of the severely stenosed ICA was
      less conspicuous if associated with a controlateral severe stenosis. The MBF of
      the BA increased significantly in the presence of the bilateral severe ICA
      stenosis and in the ICA occlusion. The MBF of the MCA was unchanged in the
      presence of various degrees of ICA stenosis. Measurement of MBF with fast PC MRA
      permits cerebropethal blood flow assessment and gives additional information in
      grading ICA stenosis. The reduced MBF of a severe ICA stenosis has to be
      considered with caution since it depends also on the status of the controlateral
      ICA and may be considered a confident parameter only in case of unilateral
      carotid stenosis.

PMID- 15503042
TI  - Manifestation of Hodgkin's lymphoma in an adrenal myelolipoma.
AB  - Adrenal myelolipomas are benign tumors histologically consisting of fat and bone
      marrow. The computed tomography findings of Hodgkin's lymphoma manifested in an
      adrenal myelolipoma are described. This collision tumor constellation has not
      been reported previously.

PMID- 15503043
TI  - Abdominal aortic aneurysms: virtual imaging and analysis through a remote web
      server.
AB  - The study describes the application of a web-based software in the planning of
      the endovascular treatment of abdominal aortic aneurysms (AAA). The software has
      been developed in the framework of a 2-year research project called Aneurysm
      QUAntification Through an Internet Collaborative System (AQUATICS); it allows to
      manage remotely Virtual Reality Modeling Language (VRML) models of the abdominal
      aorta, derived from multirow computed tomography angiography (CTA) data sets, and
      to obtain measurements of diameters, angles and centerline lengths. To test the
      reliability of measurements, two radiologists performed a detailed analysis of
      multiple 3D models generated from a synthetic phantom, mimicking an AAA. The
      system was tested on 30 patients with AAA; CTA data sets were mailed and the time
      required for segmentation and measurement were collected for each case. The Bland
      Altman plot analysis showed that the mean intra- and inter-observer differences
      in measures on phantoms were clinically acceptable. The mean time required for
      segmentation was 1 h (range 45-120 min). The mean time required for measurements
      on the web was 7 min (range 4-11 min). The AQUATICS web server may provide a
      rapid, standardized and accurate tool for the evaluation of AAA prior to the
      endovascular treatment.

PMID- 15503044
TI  - A tamponade leading to death after radiofrequency ablation of hepatocellular
      carcinoma.
AB  - A case of hemorrhagic cardiac tamponade after radiofrequency ablation (RFA) of
      hepatocellular carcinoma (HCC) leading to death is presented. The complication
      occurred during a procedure performed under general anesthesia with an expandable
      needle system for a 2-cm HCC sited in the second segment of the liver close to
      the diaphragm. Thermal damage to the organs surrounding the liver are major
      complications of liver tumor RFA. For lesions that are adjacent to the cardiac
      cavities, a discussion of better therapeutic options remains necessary and has to
      take into account the effectiveness and complication rate of each technique.

PMID- 15503046
TI  - Intraparenchymal epidermoid tumor of the brain.

PMID- 15503045
TI  - Does the location of a vascular loop in the cerebellopontine angle explain
      pulsatile and non-pulsatile tinnitus?
AB  - The purpose was to investigate patients with unexplained pulsatile and non
      pulsatile tinnitus by means of MR imaging of the cerebellopontine angle (CPA) and
      to correlate the clinical subtype of tinnitus with the location of a blood vessel
      (in the internal auditory canal or at the cisternal part of the VIIIth cranial
      nerve). Clinical presentation of tinnitus and perceptive hearing loss were
      correlated. In 47 patients with unexplained tinnitus, an MR examination of the
      CPA was performed. Virtual endoscopy reconstructions were obtained using a 3D
      axial thin-section high-resolution heavily T2-weighted gradient echo constructive
      interference in steady state (CISS) data-set. High-resolution T2-weighted CISS
      images showed a significantly higher number of vascular loops in the internal
      auditory canal in patients with arterial pulsatile tinnitus compared to patients
      with non-pulsatile tinnitus (P<0.00001). Virtual endoscopy images were used to
      investigate vascular contacts at the cisternal part of the VIIIth cranial nerve
      in patients with low pitch and high pitch non-pulsatile tinnitus. A significantly
      different distribution of the vascular contacts (P=0.0320) was found.
      Furthermore, a correlation between the clinical presentation of non-pulsatile
      tinnitus (high pitch and low pitch) and the perceptive hearing loss was found
      (P=0.0235). High-resolution heavily T2-weighted CISS images and virtual endoscopy
      of the CPA can be used to evaluate whether a vascular contact is present in the
      internal auditory canal or at the cisternal part of the VIIIth cranial nerve and
      whether the location of the vascular contact correlates with the clinical subtype
      of tinnitus. Our findings suggest that there is a tonotopical structure of the
      cisternal part of the VIIIth cranial nerve. A correlation between the clinical
      presentation of tinnitus and hearing loss was found.

PMID- 15503047
TI  - Acute necrotizing encephalopathy.

PMID- 15503048
TI  - Erectile dysfunction after transurethral resection of the prostate: incidence and
      risk factors.
AB  - It is known that a proportion of patients who undergo transurethral resection of
      the prostate (TURP) will develop erectile dysfunction (ED). This study examined
      the incidence of ED after TURP using objective and subjective parameters and risk
      factors for the development of ED. All benign prostate hyperplasia (BPH) patients
      who were indicated for TURP had to meet the criteria of the International Index
      of Erectile Function (IIEF) 5 scores of more than 16, and with normal nocturnal
      penile tumescense (NPT) which had at least one episode of nocturnal erections
      with both base and tip rigidity exceeding 55% for at least 10 min. The patient's
      nocturnal erection were measured using Rigiscan, over two consecutive nights,
      approximately 3-4 days preoperatively and 3 months postoperatively. A total of 63
      patients were eligible for the study; the mean age was 63.3 years (range 49-85
      years). Nine (14%) patients were found to have postoperative ED. Patients who
      developed ED postoperatively had a lower IIEF-5 score and NPT parameters
      preoperatively (for all parameters, P<0.0001). For risk factors, diabetes
      mellitus were found to be a significant independent risk factor. The incidence of
      ED post-TURP using objective parameters was 14%. Without taking note of the risk
      factors, TURP is a safe procedure with regard to sexual function.

PMID- 15503049
TI  - PET and prostate cancer.
AB  - The diagnosis of prostate cancer leaves some questions without answers. The
      different diagnostic techniques are limited in three situations: (1) staging of
      the tumour: identification of node involvement, (2) quantification of the tumour
      volume and its location inside the gland, (3) premature identification of relapse
      after radical treatment. These are the three problems that we need to consider in
      the diagnosis of prostate carcinoma. Imaging techniques can tell us the
      morphological alterations in the structures and organs. Positron emission
      tomography (PET) introduces a new way of identifying damage by counting metabolic
      activity. The tracers are substances that are marked with a radioactive molecule
      that is picked up more readily by the tumours. The presence of these substances
      in a set anatomic zone means higher consumption and therefore more metabolic
      activity. The radiotracer most frequently used in PET is glucose marked with
      fluoride 18. The first studies with marked glucose and prostate tumours started
      at the end of the 1990s. There are many contradictions in the results of these
      studies due to renal elimination, which produces an accumulation in the urinary
      tract and does not correctly show the prostate zone and iliobturator nodes area,
      and its capitation by zones with inflammatory process or prostatic hyperplasia.
      Choline is a substance that is present in cellular membranes. When it is marked
      with carbon 11, it changes to a new tracer. This radiotracer has affinity with
      prostate damage and allows the better differentiation of malignant from benign
      processes. It also has the advantage of the absence of renal elimination. Trials
      that used choline marked with carbon 11 (11C choline) are beginning to obtain
      very promising results. This union of a method that identifies metabolic activity
      with an imaging technique increases the sensitivity in the diagnostic test and
      can help find the exact location of the 11C choline deposits. The PET-CT combines
      the PET with computerised tomography. The 11C choline PET-CT is presented as a
      promising technique for answering the three problems mentioned above.

PMID- 15503050
TI  - [Diabetic retinopathy. Internal medical aspects of an ophthalmologic topic].
AB  - Insight into the natural course and the clinical features of diabetic retinopathy
      as well as advances in understanding the pathogenesis and new developments for
      beneficial treatments of diabetic retinopathy have broadly enlarged during recent
      years. It is now well accepted that chronic hyperglycemia and arterial
      hypertension are the most important factors for microvascular damage in diabetes.
      Although established treatment modalities have not yet yielded prevention of
      blindness due to diabetes, there is a trend toward a broader therapeutic concept
      for patients with diabetes including general vasoprotection. In this context, the
      retina plays a major role as early retinopathy earmarks the vascular high-risk
      patient with diabetes. Accordingly, every proven measure should be taken to avoid
      what still happens in evidence-based medicine: "lost in translation."

PMID- 15503051
TI  - [Microbial keratitis following laser in situ keratomileusis. Prevention,
      differential diagnosis, and therapy].
AB  - Laser in situ keratomileusis (LASIK) is an effective option and currently one of
      the most commonly applied surgical techniques in the correction of refractive
      errors such as myopia, hyperopia, and astigmatism. In contrast to photorefractive
      keratectomy, it maintains the integrity of Bowman's membrane and the epithelium
      leading to faster visual rehabilitation as well as less pain and discomfort.
      Nevertheless, following LASIK the stroma is exposed to infectious organisms.
      Sight-threatening complications after LASIK are reported to be as rare as 1 in
      1000 procedures. However, any infectious keratitis remains potentially
      devastating. Reports about infectious keratitis following LASIK have increasingly
      surfaced in recent years. We present a review of the literature on microbial
      keratitis and present our own cases and recommendations for possible prophylaxis
      and therapy.

PMID- 15503052
TI  - [Three-dimensional ultrasound biomicroscopic examinations for haptic
      differentiation of potentially accommodative intraocular lenses].
AB  - PURPOSE: The principal ability of potentially accommodative IOLs is based on an
      axial shift of the IOL optics induced by the ciliary body action in interaction
      with a reversible change in haptic angulation. The aim of this study was to
      investigate the accommodative performance of this new IOL generation. METHOD: The
      authors have designed a test device to study IOL performance experimentally.
      These results were extrapolated to the in vivo situation in patients with
      accommodative implants. RESULTS: The 3D high-resolution presentation of the
      anterior segment of the eye allows a separation of the IOL haptic elements. In
      vitro and in the selected in vivo cases a change in haptic angulation <10 degrees
      in combination with a maximal IOL shift of 0.5 mm was found. CONCLUSIONS: The
      simulation model used in combination with 3D ultrasound biomicroscopy provides
      information about the potential of accommodative IOL designs. Conclusions
      corresponding to changes in haptic angulation during accommodation can be drawn
      and applied to the in vivo situation.

PMID- 15503053
TI  - Appetence behaviours of the triatomine bug Rhodnius prolixus on a servosphere in
      response to the host metabolites carbon dioxide and ammonia.
AB  - A combination of 1,000 ppm CO(2) plus 30-40 ppb NH(3) in an air stream induced
      Rhodnius prolixus nymphs walking on a servosphere to perform a series of
      appetence behaviours. Shortly after the onset of stimulation the nymphs turned
      sharply upwind towards the source of the chemostimuli (within 13 +/- 9 s) from
      mostly downwind and crosswind walks in the air stream alone. The mean vector
      angles of these upwind tracks were concentrated in a cone 60 degrees either side
      of due upwind. The upwind walking bugs stopped more frequently but for a shorter
      duration and walked at a higher speed than before stimulation. During stops in
      the presence of the chemostimuli the bugs frequently corrected their course
      angles and extended their forelegs to reach higher with their antennae in the
      air. In the air stream alone, R. prolixus nymphs frequently sampled the sphere
      surface with the antennae and cleaned their antennae with the foreleg tarsi.
      However, the nymphs only briefly tapped the left or right antennal flagellum on
      the corresponding first leg tarsus and never touched the servosphere surface in
      the presence of the chemostimuli. After chemostimulus removal from the air stream
      the bugs continued to respond with the same appetence responses as during
      stimulation, but walked more tortuously in a crosswind direction in an effort to
      regain contact with the chemostimuli.

PMID- 15503054
TI  - Short-term fasting induces intra-hepatic lipid accumulation and decreases
      intestinal mass without reduced brush-border enzyme activity in mink (Mustela
      vison) small intestine.
AB  - For many mammalian species short-term fasting is associated with intestinal
      atrophy and decreased digestive capacity. Under natural conditions, strictly
      carnivorous animals often experience prey scarcity during winter, and they may
      therefore be particularly well adapted to short-term food deprivation. To examine
      how the carnivorous gastrointestinal tract is affected by fasting, small
      intestinal structure, brush-border enzyme activities and hepatic structure and
      function were examined in fed mink (controls) and mink that had been fasted for 1
      10 days. During the first 1-2 days of fasting, intestinal mass decreased more
      rapidly than total body mass and villus heights were reduced 25-40%. In contrast,
      tissue-specific activity of the brush-border enzymes sucrase, maltase, lactase,
      aminopeptidase A and dipeptidylpeptidase IV increased 0.5- to 1.5-fold at this
      time, but returned to prefasting levels after 6 days of fasting. After 6-10 days
      of fasting there was a marked increase in the activity of hepatic enzymes and
      accumulation of intra-hepatic lipid vacuoles. Thus, mink may be a useful model
      for studying fasting-induced intestinal atrophy and adaptation as well as
      mechanisms involved in accumulation of intra-hepatic lipids following food
      deprivation in strictly carnivorous domestic mammals, such as cats and ferrets.

PMID- 15503055
TI  - In vivo and in vitro rapid cold-hardening protects cells from cold-shock injury
      in the flesh fly.
AB  - The capacity to undergo rapid the cold-hardening response (RCH) has been
      documented in diverse groups of insects and functions to protect against non
      freezing cold injury and to preserve physiological performance in response to
      environmental cooling. The RCH response is remarkable for the rapidity of its
      induction; however the mechanism by which insects perceive cold and transduce
      this input at the cellular level has received little attention. To test the
      hypothesis that cells from isolated tissues can undergo RCH in response to cold,
      we assessed cell viability in four tissues that had undergone either RCH (0
      degree C, 2 h followed by -8 degrees C, 2 h) or cold-shock (-8 degrees C, 2 h)
      both in vivo and in vitro from the adult flesh fly Sarcophaga crassipalpis
      (Diptera: Sarcophagidae) using fluorescent probes. Adult flies showed a
      significantly higher survival rate in the RCH group than in the cold-shocked
      group. Similarly, in all tissues tested, both in vivo and in vitro, RCH
      significantly improved cell survival compared with the respective cold-shocked
      groups. To our knowledge this is the first report to demonstrate that isolated
      cells and tissues from insects can undergo RCH. These results indicate that
      insect cells are capable of cold-sensing without neuroendocrine mediation; direct
      induction at the cellular level also helps to explain the swiftness of the RCH
      response.

PMID- 15503056
TI  - Acid-base regulation in isolated gill cells of the goldfish (Carassius auratus).
AB  - Mechanisms of acid release and intracellular pH (pH(i)) homeostasis were analysed
      in goldfish (Carassius auratus) gill cells in primary culture. The rate of acid
      secretion was measured using a cytosensor microphysiometer, and pH(i) was
      determined using the fluorescent probe 2',7'-bis-(3-carboxypropyl)-5-(and-6)
      carboxyfluorescein (BCPCF). Amiloride, a Na(+) channel and Na(+)/H(+) exchanger
      (NHE) inhibitor, had no effect on pH(i), but acid secretion of the gill cells was
      significantly impaired. In the presence of amiloride, the intracellular
      acidification (achieved using the NH(4)Cl pulse technique) was more severe than
      in the absence of amiloride, and recovery from the acidosis was slowed down.
      Accordingly, acid secretion of gill cells was severely reduced in the absence of
      extracellular Na(+). Under steady-state conditions, 4,4'-diisothiocyanatodihydro
      stilbene-2,2'-disulfonic acid (DIDS), a HCO(3)(-)-transport inhibitor, caused a
      slow acidification of pH(i), and acid secretion was significantly reduced. No
      recovery from intracellular acidification was observed in the presence of DIDS.
      Bafilomycin A(1), an inhibitor of V-ATPase, had no effect on steady-state pH(i)
      and recovery from an intracellular acidification, whereas the rate of acid
      secretion under steady-state conditions was slightly reduced.
      Immunohistochemistry clearly revealed the presence of the V-ATPase B-subunit in
      goldfish gill lamellae. Taken together, these results suggest that a Na(+)
      dependent HCO(3)(-) transport is the dominant mechanism besides an NHE and V
      ATPase to control pH(i) in goldfish gill cells.

PMID- 15503057
TI  - The physics of image formation in the neuroendoscope.
AB  - INTRODUCTION: The development of the neuroendoscope has allowed neurosurgeons to
      visualize anatomic structures deep within the nervous system with minimal
      disruption of the critical overlying structures. This has enabled the development
      of an entire system of tools and techniques for maximum effective action at the
      target point through minimal corridors for the treatment of an entire spectrum of
      pathologies. DISCUSSION: The design of an optical instrument with the ability to
      illuminate deep, hidden anatomic structures and transmit those images accurately
      and brightly to the eye of the neurosurgeon poses several challenges. These
      challenges have been met by advances in lens design and optical systems
      engineering over a period of several decades leading up to emergence of the
      modern neuroendoscope. In this paper, the basic concepts of the physics of image
      formation in optical systems are reviewed with emphasis on those elements
      critical to the endoscope. CONCLUSION: A consideration of these basic concepts is
      critical to the understanding of the limitations and capabilities of the key
      instrument for neuroendoscopy.

PMID- 15503061
TI  - Spontaneous choledochal cyst rupture in a child.

PMID- 15503058
TI  - The evolution and future of minimalism in neurological surgery.
AB  - INTRODUCTION: The evolution of the field of neurological surgery has been marked
      by a progressive minimalism. This has been evident in the development of an
      entire arsenal of modern neurosurgical enterprises, including microneurosurgery,
      neuroendoscopy, stereotactic neurosurgery, endovascular techniques, radiosurgical
      systems, intraoperative and navigational devices, and in the last decade,
      cellular and molecular adjuvants. AIMS: In addition to reviewing the major
      developments and paradigm shifts in the cyclic reinvention of the field as it
      currently stands, this paper attempts to identify forces and developments that
      are likely to fuel the irresistible escalation of minimalism into the future.
      These forces include discoveries in computational science, imaging, molecular
      science, biomedical engineering, and information processing as they relate to the
      theme of minimalism. DISCUSSION: These areas are explained in the light of future
      possibilities offered by the emerging field of nanotechnology with molecular
      engineering.

PMID- 15503062
TI  - Renal fungal balls and pelvi-ureteric junction obstruction in a very low birth
      weight infant: treatment with streptokinase.
AB  - Renal candidiasis is a rare but well recognised complication of intensive care
      treatment in neonates. We report a problematic case with obstructing pelvi
      ureteric junction (PUJ) fungal balls that was refractory to standard measures of
      adequate nephrostomy drainage, pelvic irrigation with amphotericin B, and
      systemic antifungal treatment. In an attempt to avoid potentially difficult open
      surgery, a novel treatment using a streptokinase solution (3,000 IU/ml) for
      irrigation was performed. This was successful in clearing the fungal balls,
      relieving obstruction and rendering the urine sterile. The present case
      highlights a potential role for streptokinase in cases of renal candidiasis
      refractory to current treatment protocols.

PMID- 15503063
TI  - Lymphatic sparing, laparoscopic varicocelectomy: a new surgical technique.
AB  - Several surgical options are available for managing varicoceles. Although
      conventional surgery offers good surgical results, the most common long-term
      complication of surgery is the development of hydroceles, thought to be due to
      interruption in the lymphatic outflow from the subservient testis. The authors
      describe a new technique of in vivo methylene blue mapping of testicular
      lymphatic vessels at laparoscopy, allowing these vessels to be spared during
      laparoscopic varicocelectomy. This novel method of in vivo staining of lymphatic
      vessels should prevent damage to the lymphatic system and avoid the late
      development of hydroceles. A prospective multicenter trial is currently underway
      to evaluate the medium- and long-term results.

PMID- 15503064
TI  - Rare inguinal hernia forms in children.
AB  - Rare inguinal hernia forms are encountered more frequently in the laparoscopic
      technique than in the open approach. The reasons are subject to speculation. The
      incidence of unusual inguinal hernia forms was studied in a series of inguinal
      hernias corrected laparoscopically in 452 children (334 boys and 118 girls aged 4
      days--14 years, median age 1.6 years). The videos were retrospectively evaluated.
      Direct hernias were found in 10 children (2.2%), femoral hernias in five (1.1%),
      hernias en pantalon in three (0.7%), and a combination of indirect and femoral
      hernia and a combination of indirect, direct, and femoral hernia in one child
      each (0.2%). Routine videorecording during laparoscopy provides for the first
      time an objective and absolute picture of the true incidence of these unusual
      hernia forms.

PMID- 15503065
TI  - Cytoreductive surgery and intraperitoneal chemotherapy for pseudomyxoma
      peritonei.
AB  - BACKGROUND AND AIMS: Surgical improvement can be achieved in selected patients
      with pseudomyxoma peritonei (PMP) by major cytoreductive surgery and
      intraperitoneal chemotherapy (IPEC). The purpose of this retrospective study was
      to analyze morbidity, mortality, and survival following therapy. PATIENTS AND
      METHODS: Between July 1995 and September 2003, 28 patients (mean age 56 years,
      range 28-79) with PMP were operated on with the aim of complete macroscopical
      cytoreduction. Surgery was followed by IPEC. RESULTS: A macroscopically complete
      cytoreduction was achieved in 11 patients (40%). The mean operating time was 6 h
      with a mean of three peritonectomy procedures per patient. Cisplatin (15 out of
      28), mitomycin C (6 out of 28) and 5-FU (7 out of 28) were used for the
      intraoperative chemotherapy. Overall morbidity was 36%. Most frequent surgical
      complications were digestive fistulae (3 out of 28), abscesses (5 out of 28) and
      bleeding (2 out of 28). Two patients died postoperatively. Patients with low
      tumor volume (mean survival time 78+/-11 vs. 37+/-9 months, p=0.05) and complete
      cytoreduction (73+/-10 vs. 24+/-8 months, p<0.05) had an improved prognosis.
      CONCLUSIONS: Cytoreductive surgery combined with IPEC is associated with
      acceptable morbidity and mortality. Complete cytoreduction may improve survival,
      particularly in selected patients with PMP who have a low tumor volume, complete
      cytoreduction, and no organ metastases.

PMID- 15503067
TI  - [The best future prospects for social and behavioral scientific gerontology!
      Introduction to seven short contributions by award-winning junior scientists].

PMID- 15503066
TI  - Apoptosis in the intestinal mucosa of patients with inflammatory bowel disease:
      evidence of altered expression of FasL and perforin cytotoxic pathways.
AB  - BACKGROUND AND AIMS: Abnormal apoptosis may result in the persistence of
      activated intestinal T-cells in inflammatory bowel disease (IBD). We investigated
      apoptosis in distinct mucosal compartments, and the expression of Fas/Fas ligand
      and perforin in the inflamed and non-inflamed intestinal mucosa of patients with
      IBD. METHODS: Colon specimens from 15 patients with ulcerative colitis (UC) and
      inflamed and non-inflamed mucosa from 15 patients with Crohn's disease (CD) were
      analysed for densities and distribution of apoptotic cells determined by the
      terminal deoxynucleotidyltransferase-mediated dUDP-biotin nick-end labelling
      (TUNEL) method. Fas, FasL, and perforin-expressing cells were assessed by
      immunoperoxidase, and with anti-CD3, anti-CD20 and anti-CD68, by double
      immunofluorescence with confocal microscopy. Quantitative analysis was performed
      using a computer-assisted image analyser. RESULTS: Colonic lamina propria (LP)
      and epithelium from patients with UC showed higher rates of apoptosis than
      controls, but no difference was shown regarding patients with CD. In LP, co
      expression of Fas was reduced with T-cells in inflamed CD mucosa, and with
      macrophages in all patients with IBD. No difference was found in the expression
      of Fas on B-cells. Rates of FasL-expressing cells in LP were higher in IBD than
      in controls, with no correlation with the rates of apoptosis. Rates of perforin
      expressing cells in LP were greater in UC than in controls, and correlated to the
      rates of apoptosis. No difference was shown regarding the inflamed and non
      inflamed CD mucosa. Rates of FasL and perforin-expressing intra-epithelial
      lymphocytes showed no difference among groups. CONCLUSIONS: Increased expression
      of FasL in IBD colonic LP not parallelled by Fas on T-cells and macrophages may
      indicate a reduced susceptibility to the Fas/FasL-mediated apoptosis of lymphoid
      cells. Expression of perforin is correlated to the tissue damage, and may
      represent the enhancement of a distinct cytotoxic pathway in UC.

PMID- 15503068
TI  - [Socially oriented daily life in very old age--design of a qualitative study
      within the European Project ENABLE-AGE].
AB  - Social participation is an important indicator for quality of life and seems to
      decrease in very old age. However, gerontological research on social
      participation in very old aged is based on fuzzy ad hoc definitions that do not
      differentiate between the third and the fourth age. The starting point of the
      planned qualitative study within the EU project ENABLE-AGE is the assumed need
      for a specific conceptualization of social participation in very old age. To
      achieve this, semi-structured interviews (n=40) are conducted with very old
      persons in single households and analyzed according to the Grounded Theory
      approach. This methodology allows both systematic consideration of relevant
      sociological concepts on social participation in old age in the form of so-called
      "sensitizing concepts" and quantitative findings. This study will contribute to a
      valid conceptualization of social participation in very old age and theory
      empiricism-integration in sociology on old age. In addition, the societal
      potential of enhancing social participation in very old age will be explored.

PMID- 15503069
TI  - [Domestic abuse of dementia patients: data collection in a difficult research
      area].
AB  - In the context of a longitudinal dementia caregiver stress study, a short
      questionnaire was developed in order to assess domestic abuse of dementia
      patients. By embedding the sensitive topic of domestic violence in a different
      research context, good compliance in the sample could be achieved which results
      in high prevalence rates.

PMID- 15503070
TI  - [Changes in needs for assistance and care after hip fractures in the elderly].
AB  - For the prevention and rehabilitation of fall-related fractures, not only
      functional status is important. It is necessary to describe the level of help and
      care needed at the time the fracture happened and its changes after a certain
      period. Investigations of the changes in the need of help and care after a fall
      related fracture hardly exist for the Federal Republic of Germany. The first step
      in the present investigation was to analyze the changes in the need of help and
      care. In a second step, different developments of changes in the need of help and
      care after a fall-related hip fracture should be identified. Data for the present
      analysis were taken from a prospective 12-month observational survey (Fractures
      in late life). A total of 332 people aged 65 and over were assessed at two
      timepoints (T1-within the first 4 days post-fracture and T2-six months later by
      phone call). The assessed aspects were formal and informal support, financial
      support, ability to walk, cognition (only at T1) and form of housing. After the
      fall-related fracture the strain of formal and informal support increases. The
      strain of financial support and institutional care also increases. 20% of the
      patients achieved for the first time the criteria for the lowest level in the
      legal care system of Germany which indicates a higher level of need of care. 5%
      of the patients achieved post-fracture a higher level in the legal care system.
      Six different groups of patients could be identified by cluster analyses. They
      show differences in the changes in the ability to walk, form of housing,
      mortality and level of care and help. The different health status before and
      after the fall-related fracture leads to different developments post-fracture. In
      prevention and rehabilitation of patients with fall-related fractures, the
      individual needs of the subgroups should be taken into consideration.

PMID- 15503071
TI  - [Perception of resources and their meaning for well-being: age-associated
      similarities and differences among young and old adults].
AB  - Personal resources represent important determinants of life-long development.
      Since the use of the resources is a decisive factor, the perception of resources
      and changes in them is presumably crucial for the developmental success. In the
      present study, we investigated whether the perception of resources (i. e.,
      cognition, health, social network) differs between young and old individuals,
      whether the resource perception is related to well-being and whether these
      relations are identical among young and old adults. Young and old individuals did
      not differ with respect to subjective resource status and resource importance;
      however, the young experienced more gains and the old reported more losses.
      Resource status explained the highest proportion of variance in well-being in
      both age groups. Resource loss was of relevance to well-being only in the young,
      but not in the old group. Thus, the significance of resource loss seems to vary
      across the life span, which puts the notion of a universal role of resource loss
      into question. For future studies, domain-specific analyses and the investigation
      of protective mechanism are proposed.

PMID- 15503072
TI  - [Friendships in middle and older adulthood: the long arm of early childhood
      experiences].
AB  - In this study, direct associations between recalled parent-child relations and
      adult friendships and a mediation of this relationship by personality
      characteristics were examined. Furthermore, the contribution of the personality
      characteristics openness and agreeableness to friendship involvement in different
      phases of life was investigated. Data from 392 middle aged (43-46 years) and 345
      older participants (61-64 years) in the first wave of the Interdisciplinary
      Longitudinal Study of Adult Development (ILSE) were used for structural equation
      modeling. Results show that the relation between recalled mother-child
      relationship and friendship involvement in old adults is mediated by
      agreeableness. Recalled father-child relationship was associated with friendships
      in both age groups, independent of personality characteristics. Data support the
      hypothesis that openness contributes to friendship involvement in middle age,
      while agreeableness contributes to friendship involvement in old age.

PMID- 15503073
TI  - ["Geri-Aktiv"--the activation of nursing home residents].
AB  - Although being active is a central element of successful aging, we know little
      about activities which elderly people carry out in institutional environments.
      The first study's aim was to describe the importance of activation for the
      residents (n=255) and their nurses (n=171) using quantitative methods. To immerse
      into the subject we carried out qualitative interviews (n=61) to ascertain how an
      activation according to the needs of old people can be reached. With the
      background of activation and motivation theories and first results, a model was
      developed focusing on need-oriented activation. Considering the impairments in
      old age, offers for individual activation and attendance can be derived from this
      model.

PMID- 15503074
TI  - [A psychosocial training program for elderly patients with age-related macular
      degeneration: findings of a pilot evaluation study].
AB  - The purpose of this work was to develop and evaluate a psychosocial intervention
      aimed to improve quality of life of AMD patients. A total of 22 outpatients (age
      62 to 80 years) treated in the University Eye Clinic in Heidelberg were divided
      into an intervention group (n=14) and a comparison group without intervention
      (n=8). The intervention program was based on six modules carried out in five
      weekly group sessions. These modules included: (1) progressive muscle relaxation,
      (2) exchange of disease-related experiences, (3) connection between thought,
      emotion, and behavior, (4) activation of available resources, (5) general problem
      solving skills and (6) information exchange. Pre-post assessment addressed a set
      of standardized emotional and behavioral outcome measures. Findings revealed that
      the intervention group showed improvement or prevention of additional loss in
      emotional as well as in behavioral outcomes, while the comparison group did not.
      Results are interpreted as initial evidence that the developed program is able to
      improve the quality of life in patients suffering from AMD.

PMID- 15503075
TI  - [Salutogenesis in old age].
AB  - In this contribution, the significance of the salutogenic model (Antonovsky) and
      its core concept-the sense of coherence-for research into "successful aging" is
      explicated on the background of a gerodynamic perspective (Schroots). Common to
      both approaches is the idea that the basic principle of life is based on
      imbalance, disease, and suffering (heterostasis). According to this pessimistic
      view, aging is considered as the individual time dimension on which these
      inevitable impairments in biological, behavioral, and social respects take place.
      The continuous increase in entropy (disorder) will finally result in the death of
      the organism. In the face of gerontological research showing variability and
      individual plasticity in aging processes-especially for the third age-, the
      salutogenic question is why some people generally become (very) old and stay
      healthy. According to the salutogenic model, the sense of coherence determines
      the (re-)production of order over the life span and mediates the relationship
      between resources/stressors and health outcome. Considering
      activity/disengagement theory and the selective optimization with compensation
      model as an example, the integrative potential of the salutogenic model is shown.
      Finally, the value of the salutogenic model for the fourth age is discussed.
      Healthy aging is one chance of human existence, but in no way a collective duty
      that should be imposed on the individual.

PMID- 15503076
TI  - [Motor competence and quality of life in elderly active persons].
AB  - Physical activity is a vital pre-condition for healthy aging and well-being.
      While the association between objective and subjective health in old age has
      extensively been investigated, the relationship between objective motor
      competence-the capability of mastering motor demands in everyday life adequately
      by using motor resources optimally-and subjective health-related quality of life
      has not been studied yet. In an interdisciplinary study, 168 active seniors (36
      men) at the mean age of 67 (range: 59-89) underwent a test battery assessing
      motor resources and two objective domains of everyday life motor competence
      "Perceiving and Reacting" and "Mastering Complex Situations". Subsequently,
      participants rated their mental, physical, social, functional health and life
      satisfaction by questionnaire. Motor competence domains were age-dependent; the
      strongest decrease was found for "Mastering Complex Situations". Only "Mastering
      Complex Situations" was predicted by motor resources: competent seniors in this
      domain were faster in motor activity, simple reactions, body movements following
      acoustic and optic signals, and showed a stronger handcraft and a higher
      mobility. Overall, health-related quality of life was contingent upon motor
      competence: physical and functional health and-to a lesser extent-mental health
      and life satisfaction showed a systematic but moderate relationship to both motor
      competence domains. The results emphasize the significance of age-compatible and
      everyday life-adjusted physical activity for the well-being of elderly persons.
      Even active elderly persons show deficits in motor competence and should be
      trained, taking into account individual resources and flaws.

PMID- 15503077
TI  - [Basal metabolic rate and energy expenditure in the elderly].
AB  - The purpose of this study was to investigate energy requirements in healthy
      elderly subjects. Total daily energy expenditure (TEE) and resting metabolic rate
      (RMR) were measured by the doubly labeled water technique and indirect
      calorimetry in 36 healthy free living elderly men and women. Over a 15 day period
      additional measurements were made of dietary intake, physical activity and body
      composition. TEE did not differ between women and men (2941+/-439 vs 2965+/-543
      kcal/d; p=ns), ranging from 2124 to 3968 kcal/d. Resting metabolic rate was
      significantly lower in women compared to men (1345+/-194 vs 1543+/-303 kcal/d;
      p=0.016). The TEE data were compared to the food diaries. Women and men
      underestimated their food intake significantly. TEE varies greatly within elderly
      subjects due to the variation in body weight and physical activity.

PMID- 15503078
TI  - [Activities offered in nursing homes--a study of usage and satisfaction].
AB  - The following survey aims to ascertain the range of activities offered by
      different nursing homes, the extent to which residents use these activities as
      well as the satisfaction of residents and nursing staff concerning these
      activities. Focus is put on activating activities and activities of residents'
      own initiative. The analysis, which is based on 255 residents and 171 nursing
      staff from 11 nursing homes, shows a clear distinction between the various homes
      as to their ranges of activities. Activation in the home's everyday life is
      mainly done following the "watering-can principle", which means that it does not
      take into consideration the residents' individualities. The study provides clear
      evidence that the possibility to actively participate in the home's everyday life
      or to follow one's own interests makes residents feel highly satisfied. The fact
      that some residents as well as those nursing them place more importance on
      activities than others shows that the attitude towards aging is still
      characterized by the deficit model.

PMID- 15503080
TI  - [Short-term care after hospitalization: influencing factors for discharge to the
      patient's own home environment].

PMID- 15503079
TI  - [Evaluation of guided conversation groups for family caregivers of dementia.
      Results of the GENA project in Mecklenburg-Vorpommern].
AB  - The GeNA project (Gerontopsychiatric network of work with family caregivers
      Mecklenburg-Vorpommern) has focused basically on the support of family caregivers
      of demented old people in guided conversation groups along with setting up a
      supporting network for this target group within the framework of the Federal
      Ministry for Senior Citizens, Family and Youth model program "Future Structures
      of Old People's Welfare".The integrative counselling approach developed for the
      preservation and restoration of the family balance and for the reduction of care
      burden was investigated with regard to its effectiveness in case of meaningful
      indicators in a pre-post-design at ten locations. For the entire sample, the
      expected burden reductions were found only occasionally and with just a slight
      downward trend in the fields "physical exhaustion", "health trouble", "deficiency
      in the realm of social relations" and "utilization of professional support".
      There are only a few changes according to the measured personality traits out of
      the construct realm of filial maturity.A differentiating analysis of the
      caregivers' assessments defines two types of family caregivers (filial more
      mature vs. filial more immature caregivers) from the inquiry data of the
      beginning of group participation which differ from each other most significantly
      concerning the changes of interest during the progress of intervention:Whereas
      the emotional more independent family caregivers seem to profit less by the
      participation of this type of a guided conversation group, the caregivers, who
      show problematic filial patterns of ties with the care recipients to a higher
      degree, are able to use the participation for a distinct decrease of care burden.
      This contrary effect of group participation of the two types of personalities of
      caregivers can possibly be seen as a diagnostic indication for the selection of
      potential participants of similar group support offers. In view of the small
      sample size these results should be used with caution and first of all to
      generate more profound hypotheses for the specific fit of offer and demand of
      different kinds of group support for the relatives of demented old people.

PMID- 15503084
TI  - Current concepts and applications of coronary venous retroinfusion.
AB  - Retroinfusion of the coronary veins has gained attention for therapeutic
      approaches which target drugs, genes or cells to ischemic myocardium. Besides
      anatomy of the coronary venous system, the pressure flow relationship during
      retroinfusion and the efficacy of pressure-regulated selective retroinfusion for
      targeted delivery of drugs is reported. Moreover, we describe adenoviral and
      liposomal gene transfer into ischemic and nonischemic myocardium, outline studies
      in chronic ischemic preclinical models treated by retroinfusion of pro-angiogenic
      agents and discuss the impact of retroinfusion for cell-based regenerative
      therapy of the diseased myocardium.

PMID- 15503088
TI  - Natural history and pathogenesis of the patella clunk syndrome.
AB  - INTRODUCTION: The current study aims to test the importance of the design of
      total knee prostheses in the 'patella clunk syndrome', which is one of the
      possible patellofemoral complications that can occur after total knee
      replacement. MATERIALS AND METHODS: Three patient cohorts consisting of 75
      consecutive patients with 80 Insall-Burstein II (IB II) total knee replacements;
      57 patients with 60 Anatomic Modular Knee (AMK) total knee replacements; and 103
      patients with 106 Low Contact Stress Rotating Platform (LCS) total knee
      replacements were studied during the period from 1995 to 2001. This was an
      unselected series of elderly patients with knee arthritis of comparable
      demographics; we excluded only those patients receiving revision surgery. We
      recorded the preoperative and postoperative Knee Society scores, and the patient
      subgroups with postoperative patellofemoral complications were analysed in detail
      and were serially followed up. Radiological analysis followed the recommendation
      of the Knee Society, and the degree of pain was recorded on a visual analogue
      scale. Also, since the majority of patients with patella clunk syndrome had
      refused operation and were followed up for several years, an idea of the natural
      history of this condition was obtained. RESULTS: The relative frequency of
      occurrence of patella clunk syndrome among patients with the IB II, AMK, and LCS
      prostheses was 8.8%, 3.3%, and 0%, respectively. The calculated p value is
      strongly significant when comparing the IB II group with the LCS group (p<0.01);
      and of borderline significance when comparing the AMK with the LCS group
      (p=0.05); and not statistically significant between the IB II and AMK groups
      (p=0.19). Analysis of the results also showed that about half of the patients who
      underwent conservative treatment still had incapacitating symptoms after several
      years of follow-up, while the other half showed progressive improvement over
      time. CONCLUSION: Given a good surgical technique in component placement and
      debridement of the peripatella synovium, the design of a total knee prosthesis
      has a strong bearing on the incidence of the patella clunk syndrome. The natural
      history of the patella clunk syndrome reveals that for as yet uncertain reasons
      about 50% will improve with time even when given conservative treatment.

PMID- 15503089
TI  - Cyclosporin A-induced hair growth in mice is associated with inhibition of hair
      follicle regression.
AB  - BACKGROUND: Cyclosporin A (CsA) often causes hair growth in transplant
      recipients. Our objectives were to evaluate the effect of CsA on follicular hair
      keratinocyte growth in nude mice by assessing their proliferation in vivo, and to
      assess the ability of CsA to prevent follicular keratinocyte apoptosis in vivo
      and chemotherapy-induced keratinocyte apoptosis in vitro. METHODS: Nude mice were
      fed various daily doses of CsA (10-100 mg/kg). Dorsal skin sections stained with
      hematoxylin and eosin, followed by immunostaining with 4-deoxybromouridine, were
      examined for determination of hair follicle number and hair follicle keratinocyte
      proliferation. Follicular keratinocytes were isolated and examined for apoptotic
      status. Apoptosis was induced in vitro in a keratinocyte cell line by 4
      hydroperoxycyclophosphamide. The antiapoptotic effects of various CsA
      concentrations (0.1-5 microg/ml) were measured by annexin-V/propidium iodide
      binding. RESULTS: CsA caused a dose-dependent increase in the number of hair
      follicles but had no effect on follicular keratinocyte proliferation. Treatment
      with CsA decreased the number of apoptotic follicular keratinocytes. In vitro,
      there was a dose-dependent inhibition of the extent of early and late apoptosis
      of treated keratinocytes. CONCLUSION: CsA may induce hair growth by increasing
      the number of hair follicles and inhibiting apoptosis of follicular
      keratinocytes, thereby delaying hair follicle regression.

PMID- 15503090
TI  - A recombinant fragment of the fibronectin-binding protein of Staphylococcus
      aureus inhibits keratinocyte migration.
AB  - Staphylococcus aureus is a common wound-infecting organism which can interact
      with cells via the extracellular matrix protein fibronectin (FN). The aim of this
      study was to determine the effect of the FN-binding protein (FnBP) of S. aureus
      on the behaviour of a human skin keratinocytes cell line (UP). FN-coated plates
      and Transwell membranes were exposed to a recombinant protein encompassing the D1
      D4 repeat region of S. aureus FnBPB (rFnBPBD1-D4) before cell adhesion and
      migration assays. The influence of this protein on migration into a wounded area,
      cell cycle progression and endogenous cellular FN assembly was also assessed. The
      rFnBPBD1-D4 protein potently inhibited S. aureus entry into UP keratinocytes but
      had no effect on cell adhesion to FN substrate. It inhibited UP keratinocyte
      Transwell migration by 17% (P= 0.04) and 31% (P=0.02) at 10 and 100 microg/ml,
      respectively. In the wound assay, 100 microg/ml of rFnBPBD1-D4 protein reduced
      the migration area by approximately 30%. No differences in cell cycle progression
      were observed. In the presence of rFnBPBD1-D4, most of the cellular FN matrix on
      the cell surface and along the cell filopodia seen in untreated cells was absent.
      Interaction of S. aureus FnBPs with FN may influence cell behaviour and thus play
      a role in delayed epithelial closure in infected healing wounds.

PMID- 15503092
TI  - Germline cyst development and imprinting in male mealybug Planococcus citri.
AB  - In the epigenetic modifications involved in the phenomenon of imprinting, which
      is thought to take place during gametogenesis, one of the primary roles is
      exerted by histone tail modifications acting on chromatin structure. What is
      more, in insects like mealybugs, with a lecanoid chromosome system, imprinting is
      strictly related to sex determination. In many diverse species gametes originate
      in specific, highly evolutionarily conserved structures called germline cysts.
      The use of staining techniques specific for fusomal components like F-actin has
      allowed us to describe for the first time the morphogenesis of male germline
      cysts in the mealybug Planococcus citri. Antibodies to anti-methylated lysine 9
      of histone H3 (MeLy9-H3) and anti-heterochromatin protein 1 (HP1) were used
      during cyst formation to investigate the involvement of these epigenetic
      modifications in the phenomenon of imprinting and their possible concerted action
      in sex determination in P. citri. These observations indicate: (i) a specific
      role for F-actin in the segregation, typical of the lecanoid chromosome system,
      of genomes of paternal origin; (ii) that the two vital gametes originating from a
      given meiosis, although carrying the same genome, differ in the levels of both
      MeLy9-H3 and HP1, one of them being more heavily labelled by both antibodies.

PMID- 15503093
TI  - Genetic approaches to solving common diseases.
AB  - The pathway to solving simple Mendelian inherited neurological disease is now
      well established. Barely a month goes by without new linkage data or mutations in
      a novel gene being reported. These developments are giving insights into a range
      of neurological conditions from the cortex to the muscle. However, most of these
      diseases are individually rare, and one of the major challenges facing
      neuroscience is to devise methods to find the genetic variants that confer risk
      of common diseases and differential response to treatment. This latter area is an
      important emerging field known as pharmacogenomics. Unlike Mendelian genetics
      where effective strategies are well established, the strategies for detecting
      moderate genetic effects in populations have been problematic. It is likely that
      a combination of techniques will be used, involving both linkage analysis and
      linkage disequilibrium mapping. In this review we consider some of the approaches
      that can be taken to resolve the common genetic variation underlying common
      disease.

PMID- 15503094
TI  - Myotonic dystrophy type 2 and related myotonic disorders.
AB  - The myotonic dystrophies are a group of dominantly inherited disorders
      characterized by muscle wasting, myotonia, cataracts, hypogonadism and other
      system manifestations. Myotonic dystrophy type 1 (DM1) results from an unstable
      expansion of a CTG repeat in 3' UTR of the DM protein kinase (DMPK) gene on
      chromosome 19q 13.3. Myotonic dystrophy type 2 (DM2) is caused by an unstable
      expansion of a CCTG tetraplet repeat in intron 1 of the zinc finger 9 (ZFN9 gene)
      on chromosome 3q 21.3. However, the clinical diagnosis of DM2 is more complex
      than that of DM1, and conventional molecular genetic methods used for diagnosis
      of DM1 are not helpful for DM2. We here describe the detailed clinical,
      laboratory and biomolecular tests to identify DM2 and related myotonic disorders.
      At present, foci of accumulated noncoding CCTG repeat RNA (ribonuclear
      inclusions) in the cell nuclei are thought to interfere with the regulation and
      expression of several genes at the basis of multisystemic aspects of myotonic
      dystrophy type 2.

PMID- 15503095
TI  - Cerebral microbleeds in patients with hypertensive stroke. Topographical
      distribution in the supratentorial area.
AB  - OBJECTIVE: To analyse the topography of cerebral microbleeds (CMBs) visualized by
      T2*-weighted gradient-echo MR imaging in the supratentorial brain area, based on
      the anatomical classification of the regions and the arterial territories.
      BACKGROUND: CMBs are associated with hypertension and the risk of intracerebral
      hemorrhage; however, little is known about the cerebral topography of CMBs.
      METHODS: We examined 164 consecutive patients with hypertensive stroke who
      underwent T2*-weighted gradient-echo MRI. The anatomical locations and the
      vascular territories of the CMBs were determined in the subcortical white matter,
      basal ganglia/internal capsule and thalamus along the standard axial slices.
      RESULTS: We detected 2,193 CMBs in 98 patients (13.4+/-39.0 per patient). The
      CMBs showed a significant predilection for the temporo-occipital area of the
      subcortical white matter, the posterolateral part of the upper putamen, and the
      lateral nuclei of the mid-level thalamus. The most common arterial territories
      were those of the middle-posterior cerebral artery in the white matter, the
      middle cerebral artery in the basal ganglia, and the thalamogeniculate artery in
      the thalamus. CONCLUSIONS: These findings were quite similar to the cerebral
      topography of intracerebral hemorrhage described in the literature. Our results
      suggest that CMBs are regionally associated with intracerebral hemorrhage.

PMID- 15503096
TI  - Cerebral autoregulation improves in epilepsy patients after temporal lobe
      surgery.
AB  - Patients with temporal lobe epilepsy (TLE) often show increased cardiovascular
      sympathetic modulation during the interictal period, that decreases after
      epilepsy surgery. In this study, we evaluated whether temporal lobectomy changes
      autonomic modulation of cerebral blood flow velocity (CBFV) and cerebral
      autoregulation. We studied 16 TLE patients 3-4 months before and after surgery.
      We monitored heart rate (HR), blood pressure (BP), respiration, transcutaneous
      oxygen saturation (sat-O(2)), end-expiratory carbon dioxide partial pressure
      (pCO(2)) and middle cerebral artery CBFV. Spectral analysis was used to determine
      sympathetic and parasympathetic modulation of HR, BP and CBFV as powers of signal
      oscillations in the low frequency (LF) ranges from 0.04-0.15Hz (LF-power) and in
      the high frequency ranges from (HF) 0.15-0.5Hz (HF-power). LF-transfer function
      gain and phase shift between BP and CBFV were calculated as parameters of
      cerebral autoregulation. After surgery, HR, BP(mean), CBFV(mean), respiration,
      sat-O(2), pCO(2) and HF powers remained unchanged. LF-powers of HR, BP, CBFV and
      LF-transfer function gain had decreased while the phase angle had increased
      (p<0.05). The reduction of LF powers and LF-gain and the higher phase angle
      showed reduced sympathetic modulation and improved cerebral autoregulation. The
      enhanced cerebrovascular stability after surgery may improve autonomic balance in
      epilepsy patients.

PMID- 15503097
TI  - Differences in number, size and location of intracranial microembolic lesions
      after surgical versus endovascular treatment without protection device of carotid
      artery stenosis.
AB  - BACKGROUND AND PURPOSE: The benefit of carotid endarterectomy in symptomatic high
      grade stenosis has long been proven. The role of angioplasty as an alternative is
      still a matter of debate. We compared the occurrence of intraprocedural
      microembolic signals and ischemic lesions between carotid endarterectomy (CEA)
      and carotid angioplasty with stent placement (CAS) without a protection device.
      METHODS: 88 patients who underwent a CEA and 41 patients who underwent CAS were
      prospectively investigated. One day before and after the intervention diffusion
      weighted MRI-studies were obtained. In 21 CEA and 18 CAS patients transcranial
      Doppler (TCD) monitoring was performed during the procedure to detect
      microembolic signals (MES). RESULTS: DWI-lesions could be detected after
      intervention in 17% of the CEA patients compared with 54% of the CAS patients
      (p<0.005). The median lesion volume was 0.08 cm(3) in the CEA group and 0.02
      cm(3) in the CAS group (p<0.001). Ischemic complications consisted of 2 strokes
      (2.3%) with symptoms lasting more than seven days in the CEA group and 1 stroke
      (2.4 %) in the CAS group. The median number of MES in the CEA group was 17 versus
      61 in the CAS group (p<0.001). No significant correlation was found between the
      total number of MES and ischemic lesions in either group. CONCLUSION: A larger
      number of emboligenic particles with smaller volume is detached during CAS.
      Additionally DWI lesions were observed in different territories after CAS but not
      after CEA. Conventional TCD emboli detection is not useful to compare
      interventional therapies of the carotid arteries.

PMID- 15503098
TI  - On the early diagnosis of IVIg-responsive chronic multifocal acquired motor
      axonopathy.
AB  - Multifocal acquired motor axonopathy (MAMA) is a treatable, immune mediated motor
      neuropathy with purely axonal electrophysiological features. Distinction from
      degenerative neuronopathies such as progressive muscular atrophy (PMA) or early
      motor neuron disease (MND) can be difficult because of the similar clinical and
      electrophysiological findings. Here, we report the clinical, electrophysiological
      and laboratory findings in 6 patients with MAMA. Electrophysiological testing
      showed purely axonal findings with evidence of pathological spontaneous activity
      and chronic neurogenic changes. Of particular note, pathological spontaneous
      activity in paraspinal myotoms was not detectable in any of the patients even
      though it had been documented in peripheral muscles of the corresponding
      myotome(s). Elevated serum ganglioside antibody levels,most frequently anti-GD1a
      antibodies, were present in all 6 patients. IV Ig treatment led to clinical
      improvement in all but one patient, who showed an allergic response when exposed
      to IVIg. Our findings indicate that paraspinal EMG and anti-GD1a antibodies can
      facilitate the early identification of treatable, IVIg responsive, patients with
      MAMA.

PMID- 15503099
TI  - Gender-related effect of clinical and genetic variables on the cognitive
      impairment in multiple sclerosis.
AB  - BACKGROUND: Cognitive impairment may occur at any time during the course of
      multiple sclerosis (MS), and it is often a major cause of disability in patients
      with the disease. The APOE-epsilon4 allele is the major known genetic risk factor
      for late onset familial and sporadic Alzheimer's Disease (AD), and it seems to be
      implicated in cognitive decline in normal elderly persons. OBJECTIVE: To
      investigate the clinical and genetic variables that can be associated with the
      cognitive decline in patients with MS. METHODS: Five-hundred and three patients
      with clinically definite MS underwent a battery of neuropsychological tests and,
      according to the number of failed tests, were divided into cognitively normal and
      impaired. All patients were genotyped for APOE gene polymorphisms. RESULTS: Fifty
      six percent of MS patients showed, to different extents, cognitive impairment.
      Cognitive decline was predominant in men and was associated with disease
      duration, Kurtzke Expanded Disability Status Scale (EDSS) score, a low level of
      education, and, interestingly, the epsilon4 allele of the APOE gene. By contrast,
      cognitive impairment in women was independent of any investigated variable.
      CONCLUSION: The findings demonstrate that clinical and genetic factors play a
      role in men affected by MS developing cognitive impairment.

PMID- 15503101
TI  - Timing the valve replacement in infective endocarditis involving the brain.
AB  - Neurological complications are very frequent in patients with infective
      endocarditis (20-40 %). In these patients it is unclear at what time a valve
      replacement should be performed. In order to develop a data based recommendation
      we studied 12 patients of our own and analyzed 228 patients from the literature.
      We included patients with valve replacement after a neurological complication of
      endocarditis and documented the time between manifestation and operation and the
      outcome. Based on these 240 patients we calculated the risk of neurological
      deterioration after the valve replacement. After brain infarction this risk is
      20% within three days, 20-50% between day 4 and 14, but declines to < 10% after
      14 days and < 1% after 4 weeks. Valve replacement within the first four weeks
      after intracranial hemorrhage has been reported to be successful only in
      individual cases. The risk of deteriorating declines later to 15%. Based on these
      limited data we suggest that valve replacement in patients with brain infarction
      should be considered within the first 72 hours if they have severe heart failure,
      otherwise after four weeks. Only a few selected patients with intracranial
      hemorrhage and progressive heart failure might benefit from valve replacement
      within the first four weeks. For all other neurological complications there are
      no reliable data. We propose a structured approach depending on cardiac and
      neurological complications and the time course of the disease.

PMID- 15503100
TI  - Suppression of immune system genes by methylprednisolone in exacerbations of
      multiple sclerosis. Preliminary results.
AB  - Acute relapses of multiple sclerosis (MS) are treated with intravenous
      methylprednisolone (IVMP), which speeds recovery from exacerbation. It is known
      that IVMP suppresses the immunological activation which occurs during an acute
      attack of MS. However, the specific target genes affected by this therapy remain
      obscure. A cDNA microarray for 448 genes was used to identify the target genes in
      IVMP therapy. Total RNA was isolated from peripheral blood mononuclear cells
      derived from six MS patients immediately before and after completion of therapy.
      IVMP significantly reduced mRNA levels for T-cell-specific transcription factor 7
      (p=0.02), T-cell-specific protein-tyrosine kinase (p=0.02), T-cell surface
      glycoprotein CD5 (p=0.05) and interferon-stimulated gene factor 3 gamma subunit
      (p=0.04). Significantly increased expression was found for eosinophil-derived
      neurotoxin (p=0.05). The suppression of expression of genes associated with T
      cell differentiation and antigen-specific T-cell activation detected in this
      study may contribute to the beneficial effect of MP in relapses of MS.

PMID- 15503103
TI  - Mutation at the SCA17 locus is not a common cause of primary dystonia.
AB  - Spinocerebellar ataxia type 17 (SCA17) is a dominant progressive
      neurodegenerative disorder, caused by a triplet repeat expansion within the TATA
      binding protein. As well as ataxia and dementia, Parkinsonism and dystonia are
      common in SCA17. In some pedigrees focal dystonia in the absence of ataxia has
      been described as a main clinical feature. To evaluate the relevance of SCA17
      mutations for primary dystonia, we examined the TBP repeat expansion in a series
      of 288 patients with different subtypes of primary torsion dystonia. We did not
      find any repeat sizes in the pathogenic range. We conclude that the SCA17 repeat
      expansion is not a common cause of familial and sporadic dystonia.

PMID- 15503102
TI  - Large artery ischaemic stroke in severe acute respiratory syndrome (SARS).
AB  - Of the 206 patients who contracted Severe Acute Respiratory Syndrome (SARS) in
      Singapore five developed large artery cerebral infarctions. Four patients were
      critically-ill and three died. Intravenous immunoglobulin was given to three
      patients. An increased incidence of deep venous thrombosis and pulmonary embolism
      was also observed among the critically-ill patients. We believe our experience
      warrants an increased vigilance against stroke and other thrombotic complications
      among critically-ill SARS patients in future outbreaks, especially if treatment
      such as intravenous immunoglobulin, that increases pro-thrombotic tendency, is
      contemplated.

PMID- 15503104
TI  - Long-term prognosis for childhood and juvenile absence epilepsy.
AB  - PURPOSE: To analyse prognostic factors for long term seizure remission in
      patients with childhood (CAE) and juvenile absence epilepsy (JAE). STUDY DESIGN:
      A retrospective analysis of a hospital based prevalence cohort. METHODS: The
      cohort consisted of 163 patients (104 females, 59 males) treated at the
      Universitatsklinik fur Neurologie, Innsbruck between 1970 and 1997. All had
      absences according to the ILAE classification. Follow up was in 1999 to 2000. We
      assessed multiple clinical and EEG factors as predictors of outcome and compared
      a classification according to the predominant pattern of seizure recurrence
      (pyknoleptic, PA or non pyknoleptic absence, NPA) with the ILAE classification
      with respect to prognosis. RESULTS: The mean age at seizure onset was 10.9 years
      (range, 3 to 27); age at follow up was 36.7 years (range, 13 to 81); duration of
      follow up was 25.8 years (range, 3 to 69). Sixty four patients (39 %) had CAE and
      64 (39 %) JAE, while 35 (22%) had typical absences but could not be clearly
      defined as either CAE or JAE, and were therefore called "the overlap group".
      Patients with JAE or patients in the overlap group developed more often
      generalized tonic clonic seizures (GTCS) (p<0.001) and myoclonic attacks (p<0.05)
      during the course of the disease. At follow up 36 (56 %) of patients with CAE, 40
      (62%) with JAE and 19 (54 %) of the overlap group were seizure free for at least
      two years (p=ns). When classified according to the predominant absence pattern at
      seizure onset 42 (51%) patients with PA and 53 (65%) with NPA were in remission
      (p=ns). In a stepwise binary logistic regression analysis the pattern of absence
      (PA or NPA) together with the later development of additional seizure types
      (myoclonias or GTCS), but not the CAE/JAE classification was predictive for long
      term lack of remission with a correct prediction of 66% of all patients.
      CONCLUSION: Only 58% of patients with absences were in remission after a long
      term follow up. CAE and JAE are closely related syndromes with large overlap of
      the age of onset. A classification according to the predominant seizure pattern
      at onset, together with later development of myoclonic attacks or GTCS is useful
      in predicting seizure remission in absence epilepsies.

PMID- 15503105
TI  - Plasma homocysteine, MTHFR C677T, CBS 844ins68bp, and MTHFD1 G1958A polymorphisms
      in spontaneous cervical artery dissections.
AB  - Mild hyperhomocysteinemia is a probable risk factor for atherosclerotic diseases
      and stroke. Recently, associations of elevated plasma homocysteine concentrations
      in the acute phase and of MTHFR 677 TT genotype with spontaneous cervical artery
      dissections (sCAD) have been reported. The purpose of this study was to test this
      hypothesis in the currently largest sample of patients with sCAD, taking into
      account known factors influencing plasma homocysteine levels. Ninety-five
      patients with past sCAD were compared with 95 age- and sex-matched healthy
      individuals. Homocysteine, vitamin B6, B12, folate, and polymorphisms of
      methylenetetrahydrofolate reductase (MTHFR C677T), cystathionine beta-synthase
      (CBS 844ins68bp) and methylenetetrahydrofolate
      dehydrogenase/methenyltetrahydrofolate cyclohydrolase/formyltetrahydrofolate
      synthetase (MTHFD1 G1958A) were assessed and any associations were analysed using
      multivariate statistics. The occurrence of sCAD was associated with elevated
      homocysteine levels with an odds ratio of 1.327 per 20 % percentile. Homocysteine
      levels were influenced by gender, smoking status, occurrence of hypertension,
      vitamin B12 and folate levels, and by the MTHFR TT genotype. MTHFR, CBS
      844ins68bp, and MTHFD1 G1958A genotype were not independently associated with the
      occurrence of sCAD. These data suggest that elevated homocysteine is associated
      with the occurrence of sCAD. The MTHFR C677T polymorphism is associated with the
      homocysteine level.

PMID- 15503106
TI  - Combined MR spectroscopic imaging and diffusion tensor MRI visualizes
      corticospinal tract degeneration in amyotrophic lateral sclerosis.
AB  - Motor neuron damage and cortical spinal tract (CST) degeneration are pathological
      features of amyotrophic lateral sclerosis (ALS). We combined whole-brain
      diffusion tensor imaging (DTI) and three-dimensional magnetic resonance
      spectroscopic imaging (MRSI) to study the CST at different locations. Eight ALS
      patients were compared with normal controls. Fractional anisotropy (FA) and mean
      diffusivity (MD), and the ratio of N-acetyl-aspartate (NAA) to creatine (Cr) were
      measured at various locations in the CST, including the subcortical white matter
      (SWM), centrum semiovale (CS), periventricular white matter (PV), posterior limb
      of the internal capsule (PIC) and cerebral peduncle (CP). Patients showed
      significantly lower FA than controls in the CST, including the SWM, CS, PV and
      PIC. Although there was a trend towards elevated MD in ALS patients, this did not
      reach statistical significance. NAA/Cr ratios were also decreased in ALS patients
      compared with normal controls, with significant differences in the SWM and PV but
      not in PIC. Combined whole-brain DTI and MRSI can detect axonal degeneration in
      ALS. Measurements of FA obtained in the SWM, CS, PV and PIC, and NAA/Cr ratios in
      the SWM and PV yield the most robust results.

PMID- 15503107
TI  - Associated autoimmune diseases in patients with the Lambert-Eaton myasthenic
      syndrome and their families.
AB  - In view of the clustering of autoimmune diseases (AIDs), we studied the frequency
      and nature of additional AIDs in patients with the Lambert-Eaton myasthenic
      syndrome (LEMS) and their family members, in both small cell lung carcinoma
      (SCLC) related and non-tumour (NT) related cases. Additional AIDs in patients
      with LEMS were assessed by interviewing the patient and studying the medical
      record. Family histories up to second-degree family members were established by
      interviewing patients, controls and family members. Forty-four patients with LEMS
      were assessed, of whom eighteen (41%) had SCLC. In the NT group seven patients
      (27%) had an additional AID, in the SCLC group two (11 %) (p=0.20). Thyroid
      disorder (five patients) and insulin dependent diabetes mellitus (two patients)
      were the most common AIDs. AIDs were significantly more frequent in families of
      patients with NT-LEMS (64%) than in control families (27%) (p=0.002), which was
      not found in SCLC-LEMS (36%, p=0.53). Affected family members were linked to the
      NT-LEMS patient through the maternal line in all cases. In conclusion, AIDs were
      more frequently found in LEMS patients without a tumour and their families, which
      could not be shown for SCLC-LEMS. This suggests that NT-LEMS shares immunogenetic
      factors with other AIDs. In families of NT-LEMS, a remarkable preponderance of
      maternal inheritance was seen, as has been reported previously in myasthenia
      gravis.

PMID- 15503109
TI  - Positive PCR for enterovirus in the cerebrospinal fluid of a child with acute
      disseminated encephalomyelitis.

PMID- 15503108
TI  - A placebo-controlled trial of gabapentin for painful HIV-associated sensory
      neuropathies.
AB  - BACKGROUND: Painful HIV-associated sensory neuropathies (HIV-SN) are a common
      complication of HIV infection. The pathogenesis is unknown and the treatment very
      limited. Gabapentin (GBP) is effective in painful diabetic neuropathy and
      postherpetic neuralgia and its effectiveness on painful HIV-SN has been reported
      anecdotally. DESIGN: Multicenter, prospective, randomised, double-blind, placebo
      controlled study. METHODS: Patients were followed for a 1-week screening, a 4
      week double-blind and a 2-week open treatment phase. GBP was initiated at 400
      mg/d, titrated over 2 weeks to 1200 mg/d, and then either maintained at this
      level or-if not beneficial-titrated to 2400 mg/d. After 4 weeks the medication
      was unblinded and the patient had the choice to begin, to maintain or to increase
      GBP to 3600 mg/d. The primary outcome measure was an improvement in median pain
      on the Visual Analogue Scale (VAS) from the screening week compared to the 4(th)
      treatment week. A secondary efficacy measure was the median sleep score (VAS).
      RESULTS: 15 patients received GBP and 11 placebo. In each group one patient
      dropped out during the doubleblind phase. Median pain (GBP 5.1; placebo 4.7) and
      sleep score (GBP 4.5; placebo 5.6) did not differ between both groups at
      baseline. In the GBP-group there was a significant decrease of the pain to 2.85 (
      44.1 %) as well as of the sleep VAS to 2.3 (-48.9 %). No significant decrease in
      the pain (median VAS=3.3, -29.8 %) as well as in the sleep score (median
      VAS=4.95, -11.6 %) was observed in the placebo-group. GBP was generally well
      tolerated. The most frequent side effect was somnolence reported in 80% of GBP
      treated patients. CONCLUSIONS: GBP was more effective than placebo in reducing
      pain and sleep interference in patients with HIV-SN.

PMID- 15503110
TI  - Parkinsonism due to bilateral basal ganglia lesions following mastocytosis
      induced hypoxia.

PMID- 15503111
TI  - 14-3-3 protein in the CSF of a patient with Hashimoto's encephalopathy.

PMID- 15503112
TI  - Recurrent cerebral embolism in a young adult with Down's syndrome. A case report.

PMID- 15503113
TI  - CSF 14-3-3 protein assay and MRI as prognostic markers in patients with a
      clinically isolated syndrome suggestive of MS.

PMID- 15503114
TI  - Angiostrongylus cantonensis meningitis presenting with facial nerve palsy.

PMID- 15503115
TI  - Reversible dysphagia and dementia in a patient with bromide intoxication.

PMID- 15503116
TI  - Complicated hereditary spastic paraplegia with thin corpus callosum: variation of
      phenotypic expression over time.

PMID- 15503120
TI  - Calcein-AM is a detector of intracellular oxidative activity.
AB  - Calcein-acetoxymethylester (calcein-AM) is a non-fluorescent, cell permeant
      compound, which is converted by intracellular esterases into calcein, an anionic
      fluorescent form. It is used in microscopy and fluorometry and provides both
      morphological and functional information of viable cells. In this study we have
      tested the response of calcein-AM to oxidation. In cell-free fluorometric assays,
      H2O2 and xanthine-xanthine oxidase induced a dose-dependent emission of the AM
      form but had no effects on calcein. Fluorometric and confocal microscopy tests on
      human fibroblasts confirmed that the cell permeant AM form is the actual sensor
      since its removal from culture medium, and its consequent back-diffusion, made
      the system insensitive to oxidative stimuli. In time-lapse confocal microscopy,
      calcein-AM detected changes in the intracellular redox state following direct
      oxidation (H2O2, xanthine-xanthine oxidase) and phorbol ester treatment.
      Comparative tests showed that calcein-AM sensitivity to oxidation is about one
      order of magnitude higher than other fluorescein derivatives. The absence of
      leakage, due to the presence of the probe in the extracellular compartment, and
      its low toxicity allow to perform experiments for prolonged times following the
      response to the same or different stimuli repeatedly applied. We propose calcein
      AM as a sensitive tool for intracellular ROS generation in living cells with
      useful applications for real-time imaging in confocal microscopy.

PMID- 15503121
TI  - Effect of perfusate temperature on pulmonary vascular resistance and compliance
      by arterial and venous occlusion in the rat.
AB  - The effect of different temperatures of perfusing fluid was tested on the
      pulmonary circulation of the rat. With increasing temperature, a decrease in
      overall pulmonary vascular resistance was observed, which depended on the
      associated reductions of arterial, venous and capillary vascular resistances. The
      highest sensitivity to temperature changes was exhibited by the venous segment.
      The overall sensitivity of pulmonary vessels to temperature caused a reduction in
      hydraulic resistance of about 1% for each 1 degrees C temperature increment.
      Compliance of pulmonary vessels increased when perfusate temperature was
      increased from between 25 and 35 degrees C to 45 degrees C, probably due to a
      direct effect of temperature on the stiffness of the vessel walls.

PMID- 15503122
TI  - Overshoot in VO2 following the onset of moderate-intensity cycle exercise in
      trained cyclists.
AB  - We have previously observed that following the onset of moderate intensity cycle
      ergometry, the pulmonary O2 uptake (VO2) in trained cyclists often does not
      increase towards its steady-state value with the typical mono-exponential
      characteristics; rather, there is a transient "overshoot". The purpose of this
      study was to systematically examine this phenomenon by comparing the VO2
      responses to two moderate-intensity work rates and one high-intensity work rate
      in trained and untrained subjects. Following a ramp exercise test to the limit of
      tolerance for the determination of the gas exchange threshold (GET) and
      VO2(peak), seven trained cyclists [mean (SD); VO2(peak) 66.6 (2.5) ml x kg(-1) x
      min(-1)] and eight sedentary subjects [VO2(peak) 42.9 (5.1) ml x kg(-1) x min(
      1)] completed six step transitions from baseline cycling to work rates requiring
      60% and 80% GET and three step transitions from baseline cycling to a work rate
      requiring 50% of the difference between GET and VO2(peak) (50%delta). VO2 was
      measured breath-by-breath and modelled using standard techniques. The sedentary
      subjects did not overshoot the steady-state VO2 at any intensity. At 60% GET, six
      of the seven cyclists overshot the steady-state VO2 [by an integral volume of 164
      (44) ml between approximately 45 and 125 s]. At 80% GET, four of the seven
      cyclists overshot the steady-state VO2 [by an integral volume of 185 (92) ml
      between approximately 55 and 140 s]. None of the cyclists showed an overshoot at
      50%delta. These results indicate that trained cyclists evidence an overshoot in
      VO2 before steady-state is reached in the transition to moderate-intensity
      exercise. The mechanism(s) responsible for this effect remains to be elucidated,
      as does whether the overshoot confers any functional or performance benefit to
      the trained cyclist.

PMID- 15503123
TI  - Moving on land: an explanation of pedometer counts in children.
AB  - The pedometer has become a popular instrument to measure physical activity in
      humans. The pedometer records physical activity as a simple, raw measure of
      ambulatory movement: the number of steps taken. Two fundamental questions of the
      use of the pedometer in pediatric research are: How many steps do children take
      in a day? How many steps should children accumulate on a daily basis? This raises
      the question: is 13,000 steps the same amount of physical activity in a 6-year
      old and a 12-year-old, given the difference in body size and stride length?
      Although previous authors have concluded that the number of steps taken is an
      equivalent amount of physical activity in children regardless of body size, the
      conclusion has not been explained by a scientific rationale or on an empirical
      basis depending on the energetics and mechanics of terrestrial locomotion and
      body size. One approach to explain this question is allometric scaling, which has
      long been utilized by comparative physiologists to show the relationships between
      body size and locomotion in animals from shrews to elephants. The aim of this
      paper was to use allometric equations, examples from comparative mammalian
      physiology, and results from previous papers that have examined the cost of
      locomotion in children to provide a better understanding of the interpretation of
      the pedometer in pediatric research. We show that empirically derived results
      confirm to allometric equations that consider the relationship between body size
      and terrestrial locomotion to cover a given distance at a given speed. Thus, the
      number of steps taken and the energy expended for a particular task is greater in
      smaller children. However, if the cost of locomotion is related to one step,
      animals tend to be equally economical, whether large or small. Therefore, the
      number of steps taken as measured by a pedometer may be interpreted as an
      equivalent level of physical activity between a 6-year-old and a 12-year-old, if
      taken at the same speed. However, the locomotor activities in daily life consist
      of walking and running up- and downhill, carrying loads, and at varying speeds or
      work intensities, and this exemplifies the limitations of the pedometer. In
      conclusion, this paper provides a better understanding of the interpretation of
      pedometer counts and highlights that the findings depend on the expression of
      physical activity.

PMID- 15503124
TI  - Cadence and performance in elite cyclists.
AB  - Many studies have attempted to describe the optimal cadence in cycling. However,
      the effect on performance has received little attention. The aim of the present
      study was therefore to examine the effect of cadence on performance during
      prolonged cycling (approximately 30 min). Fourteen male elite cyclists performed
      two or five time trials at different cadences [60, 80, 100, 120 rpm or freely
      chosen cadence (FCC)]. The total work was the same between the time trials, and
      the subjects were instructed to complete each time trial as fast as possible by
      adjusting the workload with buttons mounted on the handlebar. Accumulated work
      and cadence was visualised on a monitor. Oxygen uptake was measured continuously
      and blood lactate concentration every fifth minute. Compared to 80 rpm, finishing
      times at 60, 100 and 120 rpm were 3.5, 1.7 and 10.2% slower (P<0.05). Finishing
      time at FCC (mean 90 rpm) was indistinguishable from 80 and 100 rpm. Gross
      efficiency at 80 rpm was 2.9, 2.3, 3.4 and 12.3% larger than at 60, FCC, 100 and
      120 rpm, respectively (P<0.05). The maximal energy turnover rate was 1.7% higher
      at 100 than at 80 rpm (P<0.05). This could not, however, compensate for the 3.4%
      lower efficiency at 100 rpm. This study demonstrated that elite cyclists perform
      best at their most efficient cadence despite the maximal energy turnover rate
      being larger at a higher cadence.

PMID- 15503125
TI  - Speed of spleen volume changes evoked by serial apneas.
AB  - Diving mammals may enhance dive duration by injecting extra erythrocytes into the
      circulation by spleen contraction. This mechanism may also be important for
      apneic duration in humans. We studied the speed and magnitude of spleen volume
      changes evoked by serial apneas, and the associated changes in hematocrit (Hct)
      and hemoglobin (Hb) concentration, diving response and apneic duration. Three
      maximal apneas separated by 2 min rest elicited spleen contraction in all ten
      subjects, by a mean of 49 (27) ml (18%; P<0.001). During the same period, Hct and
      Hb rose by 2.2 and 2.4% respectively (P<0.01 and P<0.001), and apneic duration
      rose by 20 s (22% P<0.05). The mean heart rate reduction of the diving response
      was 15%, which remained the same throughout the apnea series. While the diving
      response was completely reversed between the apneas, spleen size was not
      recovered until 8-9 min after the final apnea corresponding with recovery of Hct
      and Hb. Thus, although the spleen contraction may be associated with the
      cardiovascular diving response, it is likely to be triggered by different
      mechanisms, and it may remain activated between dives spaced by short pauses. The
      two adjustments may provide a fast, quickly reversed, and a slow, but long
      lasting, way of shifting to a diving mode in humans.

PMID- 15503126
TI  - Prehension synergies during nonvertical grasping, II: Modeling and optimization.
AB  - This study examines various optimization criteria as potential sources of
      constraints that eliminate (or at least reduce the degree of) mechanical
      redundancy in prehension. A model of nonvertical grasping mimicking the
      experimental conditions of Pataky et al. (current issue) was developed and
      numerically optimized. Several cost functions compared well with experimental
      data including energylike functions, entropylike functions, and a ''motor
      command'' function. A tissue deformation function failed to predict finger
      forces. In the prehension literature, the ''safety margin'' (SM) measure has been
      used to describe grasp quality. We demonstrate here that the SM is an
      inappropriate measure for nonvertical grasps. We introduce a new measure, the
      ''generalized safety margin'' (GSM), which reduces to the SM for vertical and two
      digit grasps. It was found that a close-to-constant GSM accounts for many of the
      finger force patterns that are observed when grasping an object oriented
      arbitrarily with respect to the gravity field. It was hypothesized that, when
      determining finger forces, the CNS assumes that a grasped object is more slippery
      than it actually is. An ''operative friction coefficient'' of approximately 30%
      of the actual coefficient accounted for the offset between experimental and
      optimized data. The data suggest that the CNS utilizes an optimization strategy
      when coordinating finger forces during grasping.

PMID- 15503127
TI  - Effect of salinity on tissue architecture in expanding wheat leaves.
AB  - Salinity greatly reduces the leaf cross-sectional area of wheat (Triticum
      aestivum L.) during its development, which may lead to variation in the
      architectural properties of growing leaves that would result in a change in leaf
      physiological functions. Our objective was to characterize the effect of salinity
      on the spatial distribution of the cross-sectional area and the anatomy of large
      and small veins of a growing wheat leaf. Spring wheat was grown in a growth
      chamber in soils with or without 120 mM NaCl. Leaf 4 in both treatments was
      harvested 2-3 days after its emergence and then cut into five transverse
      segments. Examination of the transverse sections revealed that salinity
      significantly reduced the cross-sectional area, width, and radii of both
      epidermal and mesophyll cells along the leaf axis. Reduction in the cross
      sectional area and width occurred mainly at the leaf base, indicating that these
      reductions occur during the period of leaf initiation. The reduction in cross
      sectional area was attributed to a decrease in the size of the vein segments and
      a reduced number of medium and small veins. The thickness of the leaf was also
      reduced under the 120 mM NaCl treatment. A greater intercellular air space in the
      large vein segments under saline conditions was also found. The approximately 35%
      reduction observed in the number of veins under saline conditions (mainly in the
      number of small veins) may suggest that salinity reduces the capacity for re
      translocation of mineral nutrients and assimilates. The reduced area of
      protoxylem and metaxylem in midrib and large vein segments in growing tissues may
      be responsible for lower water deposition into the growth zone under saline
      conditions.

PMID- 15503128
TI  - Nitrogen uptake in relation to excess supply and its effects on the lichens
      Evernia prunastri (L.) Ach and Xanthoria parietina (L.) Th. Fr.
AB  - The aim of this study was to compare the physiological responses to increased
      nitrogen (N) supply between the nitrophytic lichen Xanthoria parietina (L.) Th.
      Fr. and the acidophytic lichen Evernia prunastri (L.) Ach. The two lichens were
      exposed to a weekly dosage of 0.05, 0.1, 0.2, 0.6 or 2.4 g N m(-2) for 2 months,
      administered as NH(4)NO(3) dissolved in artificial rainwater (1 l m(-2)). After
      the treatments, in vivo chlorophyll a fluorescence was determined to assess
      vitality; concentrations of total N, ammonium, nitrate and dominant amino acids,
      including glutamate, glutamine and arginine, were quantified in order to follow
      changes in N status; and the polyols ribitol, arabitol and mannitol were
      quantified to follow changes in the lichens' carbon (C) status. The uptake of N
      was quantified by labelling the fertiliser with (15)N in the ammonium position;
      chlorophyll a was used as an indirect marker for algal activity, and ergosterol
      as an indirect marker of fungal activity. Nitrogen uptake was higher in E.
      prunastri than in X. parietina, although the latter species may have used the
      mannitol reserves to obtain C skeletons and energy for N assimilation.
      Chlorophyll a and ergosterol concentrations remained unaltered in X. parietina
      irrespective of N dosage while ergosterol decreased with increasing N uptake in
      E. prunastri. The latter species had accumulated a large pool of ammonium at the
      highest N dosage, whilst in X. parietina a significant nitrate pool was instead
      observed. Taken together, these short-term responses to high N supply observed in
      the two lichens, and the differences between them, can partly explain the higher
      tolerance of X. parietina towards increased atmospheric N levels.

PMID- 15503129
TI  - zeta-Carotene cis isomers as products and substrates in the plant poly-cis
      carotenoid biosynthetic pathway to lycopene.
AB  - The plant carotenoid biosynthetic pathway to cyclic carotenes proceeds via
      carotene precursors in cis configuration. Involvement of individual isomers was
      elucidated by genetic complementation of desaturations and in vitro reactions of
      the corresponding enzyme. Determination of substrate and product specificity of
      phytoene and zeta-carotene desaturase revealed that 15-cis-phytoene is converted
      to 9,15,9'-tricis-zeta-carotene with 15,9'-dicis-phytofluene as intermediate by
      the first desaturase. Prior to a subsequent conversion by zeta-carotene
      desaturase, the 15-cis double bond of 9,15,9'-tricis-zeta-carotene has to be
      (photo)isomerized to all-trans. Then, the resulting 9,9'-dicis-zeta-carotene is
      utilized by zeta-carotene desaturase via 7,9,9'-tricis-neurosporene to 7,9,7',9'
      tetracis-lycopene. Other zeta-carotene isomers that are assumed to be spontaneous
      isomerization products were not converted, except for the asymmetric 9-cis-zeta
      carotene. This isomer is desaturated only to 7,9-dicis-neurosporene resembling a
      dead-end of the pathway. Prolycopene, the product of the desaturation reactions,
      is finally isomerized by a specific isomerase to all-trans-lycopene, which is a
      prerequisite for cyclization to beta-carotene. The 5-cis-lycopene and the 9-cis
      and 13-cis-beta-carotene isomers detected in leaves are thought to originate
      independently from cis precursors by non-enzymatic isomerization of their all
      trans forms.

PMID- 15503130
TI  - The spatial mismatch effect is based on global configuration and not on
      perceptual records within the visual cache.
AB  - If configurations of objects are presented in a S1-S2 matching task for the
      identity of objects a spatial mismatch effect occurs. Changing the (irrelevant)
      spatial layout lengthens response times. We investigated what causes this effect.
      We observed a reliable mismatch effect that was not influenced by a secondary
      task during maintenance. Neither articulatory suppression (Experiment 1), nor
      unattended (Experiments 2 and 6) or attended visual material (Experiment 3)
      reduced the effect, and this was independent of the length of the retention
      interval (Experiment 6). The effect was also rather independent of the visual
      appearance of the local elements. It was of similar size with color patches
      (Experiment 4) and with completely different surface information when testing was
      cross modal (Experiment 5), and the name-ability of the global configuration was
      not relevant (Experiments 6 and 7). In contrast, the figurative similarity of the
      configurations of S1 and S2 systematically influenced the size of the spatial
      mismatch effect (Experiment 7). We conclude that the spatial mismatch effect is
      caused by a mismatch of the global shape of the configuration stored together
      with the objects of S1 and not by a mismatch of templates of perceptual records
      maintained in a visual cache.

PMID- 15503131
TI  - Quantitative analysis of granule cell axons and climbing fiber afferents in the
      turtle cerebellar cortex.
AB  - The turtle cerebellar cortex is a single flat sheet of gray matter that greatly
      facilitates quantitative analysis of biotylinated dextran amine labeled granule
      cell and olivocerebellar axons and Nissl-stained granule and Purkinje neurons. On
      average, ascending granule cell axons are relatively thicker than their parallel
      fiber branches (mean +/- SD: 0.84 +/- 0.17 vs 0.64 +/- 0.12 microm,
      respectively). Numerous en passant swellings, the site of presynaptic contact,
      were present on both ascending and parallel fiber granule cell axons. The
      swellings on ascending axons (1.82 +/- 0.34 microm, n = 52) were slightly larger
      than on parallel fibers (1.43 +/- 0.24 microm, n = 430). In addition, per unit
      length (100 microm) there were more swellings on ascending axons (11.2 +/- 4.2)
      than on parallel fibers (9.7 +/- 4.2). Each parallel fiber branch from an
      ascending axon is approximately 1.5 mm long. Olivocerebellar climbing fiber axons
      followed the highly tortuous dendrites of Purkinje cells in the inner most 15-20%
      of the molecular layer. Climbing fibers displayed relatively fewer en passant
      swellings. The spatial perimeter of climbing fiber arbors (area) increased 72%
      from anteriorly (1797 microm2) to posteriorly (3090 microm2) and 104% from
      medially (1690 microm2) to laterally (3450 microm2). Differences in the size and
      spacing of en passant swellings on granule cell axons suggest that ascending
      axons may have a functionally more significant impact on the excitability of a
      limited number of radially overlying Purkinje cells than the single contacts by
      parallel fiber with multiple orthogonally aligned Purkinje cell dendrites. The
      spatially restricted distribution of climbing fibers to the inner most molecular
      layer, the paucity of en passant swellings, and different terminal arbor areas
      are enigmatic. Nevertheless, these finding provide important anatomical
      information for future optical imaging and electrophysiological experiments.

PMID- 15503133
TI  - Persistent synovitis in children with Lyme arthritis: two unusual cases. An
      immunogenetic approach.
AB  - We report on two patients with a persistent Lyme arthritis. In addition both had
      a peculiar disease history. The first patient had oligoarticular juvenile
      idiopathic arthritis in remission. Five months after an infected tick bite, she
      developed a relapse of arthritis in the same knee. We considered Lyme borreliosis
      as the possible trigger for this reactivation. The disease history of the second
      patient was that of a classical non-responder. After extensive antibiotic
      treatment osteolytic lesions became visible. MRI images suggested an erosive
      arthropathy and arthroscopy was used to investigate possible erosive arthritis.
      Studies on collected material made us consider the following hypothesis. Despite
      demonstration of a spirochete fragment in a synovial biopsy, the patient
      recovered without additional antibiotic treatment. CONCLUSION: delay of
      antibiotic treatment after appearance of erythema migrans may cause systemic
      spread of the antigen and predispose to Lyme arthritis. If intra-articular
      steroids are considered when spontaneous resolution of Lyme arthritis does not
      occur, magnetic resonance imaging of the affected joint, prior to administration,
      may provide additional information. The success of synovectomy may be related to
      removal of undegraded antigenic material which may prolong the inflammation.

PMID- 15503134
TI  - Allelic loss of 14q32 in the pathogenesis of gastrointestinal and ampullary
      malignancies: mapping of the target region to a 17 cM interval.
AB  - PURPOSE: The genetic basis for gastrointestinal and ampullary carcinomas remains
      uncertain. This study was performed to pinpoint novel chromosomal region involved
      in the tumorigenesis of gastrointestinal tract. METHODS: We screened the allelic
      status on 16 chromosomal arms in a patient with synchronous ampullary carcinoma
      and gastric cancer, but who had no family history of familial cancer syndrome.
      The significance of the shared 14q deletion was examined on clinical cohorts of
      sporadic gastric (n=12) and ampullary (n=10) carcinoma, respectively. Then, high
      density allelotype mapping was performed on 14q32 by using 23 microsatellite
      markers for the synchronous tumors. RESULTS: The synchronous gastric and
      ampullary carcinomas had no frameshift mutations in the APC, MSH2, MSH3, and MSH6
      genes. Among the microsatellite markers screened, only D14S267 showed identical
      loss in the synchronous tumors. The same allelic loss was also detected in one of
      ampullary carcinomas (10%) and two of gastric cancers (16.7%). Fine mapping of
      14q determined a minimally deleted region between D14S65 and D14S1010 (17
      centiMorgans) for the synchronous tumors. CONCLUSIONS: This study illustrates a
      paradigm using molecular genetic approach in identifying chromosome 14q32 that
      may harbor a tumor suppressor gene involved in the pathogenesis of a subset of
      gastrointestinal and ampullary malignancies.

PMID- 15503135
TI  - Heterocyclic complexes of ruthenium(III) induce apoptosis in colorectal carcinoma
      cells.
AB  - PURPOSE: The ruthenium complex salt indazolium trans-[tetrachlorobisindazole
      ruthenate(III)] (KP1019) and the analogous sodium salt KP1339 are effective tumor
      inhibiting drugs in experimental therapy of autochthonous colorectal carcinomas
      in rats. This paper examines the cell biological mechanisms underlying their
      antineoplastic effects. METHODS: Colorectal tumor cell lines were used to analyze
      uptake of the ruthenium(III) complexes into the cells and the mechanism as well
      as the efficacy of their cytotoxic effects. RESULTS: KP1019 and KP1339 are
      efficiently taken up into the cells: 100 microM ruthenium(III) complex in the
      growth medium led to the uptake of 120-160 ng ruthenium per 10(6) cells within 30
      min. Uptake of KP418 was tenfold lower correlating with its lower cytotoxic
      efficiency. KP1019 and KP1339 induced apoptosis in SW480 and HT29 cells
      predominantly by the intrinsic mitochondrial pathway as indicated by loss of
      mitochondrial membrane potential. Correspondingly sensitivity of the cells
      paralleled expression of bcl(2) while it was only slightly affected by mutations
      in Ki-ras. CONCLUSIONS: Our data demonstrate that trans-[tetrachlorobisindazole
      ruthenate(III)] complex salts are promising candidate drugs in the second-line
      treatment of colorectal cancers resistant to other cytostatic drugs and has been
      introduced into phase I clinical trials.

PMID- 15503137
TI  - Serum-soluble interleukin-2 receptor (sIL-2R) level determines clinical outcome
      in patients with aggressive non-Hodgkin's lymphoma: in combination with the
      International Prognostic Index.
AB  - PURPOSE: The aim of the present study was to assess the prognostic significance
      of serum soluble interleukin-2 receptor (sIL-2R) in aggressive non-Hodgkin's
      lymphoma (NHL). METHODS: One hundred and thirteen consecutive patients with
      previously untreated aggressive NHL (diffuse large B-cell lymphoma, 96;
      peripheral T-cell lymphoma, 17) prospectively participated in this study between
      1995 and 2001. The patients were treated with 6-8 cycles of a CHOP or THP
      (pirarubicin)-COP regimen. RESULTS: A high serum sIL-2R level (2,000 U/ml and
      over) at onset was associated with a low complete remission rate. Patients with
      high sIL-2R had significantly lower survival rates (5-year, 24%) than those with
      low sIL-2R (under 2,000 U/ml) (74%) (P<0.01). Multivariate analysis employing sIL
      2R levels and conventional prognostic factors demonstrated that high sIL-2R,
      presence of B-symptoms, and advanced age (60 years and older) were significantly
      unfavorable variables for overall survival. In addition, we attempted to use sIL
      2R in combination with the International Prognostic Index (IPI). The patients in
      the high (H) risk group and those with high sIL-2R in the low-intermediate
      (LI)/high-intermediate (HI) risk group had significantly lower survival rates
      than the patients in the low (L) risk group and those with low sIL-2R in the
      LI/HI risk group (P<0.001). CONCLUSION: The results suggest that a high serum sIL
      2R level predicts a poor prognosis in aggressive NHL and may be a useful
      biomarker for selecting appropriate treatment when used in combination with the
      IPI.

PMID- 15503139
TI  - The tamoxifen-induced suppression of telomerase activity in the human
      hepatoblastoma cell line HepG2: a result of post-translational regulation.
AB  - PURPOSE: Patients with advanced hepatocellular carcinoma (HCC) have shown to
      benefit from tamoxifen treatment. The mechanisms of tamoxifen action in HCC,
      however, are not yet clearly understood. Results from studies on the human
      hepatoblastoma cell line HepG2 provide evidence that estrogen-receptor-alpha
      independent antiproliferative actions of tamoxifen in HCC are mediated by the
      suppression of telomerase activity [5]. MATERIALS AND METHODS: We investigate the
      pathway of the tamoxifen-induced down-regulation of telomerase activity, using
      HepG2 cells incubated over 24 h or 48 h in the presence of 20 microM tamoxifen.
      RESULTS: The transcriptional levels of the three telomerase core components-human
      telomerase RNA (hTR), human telomerase reverse transcriptase (hTERT) (all
      variants), and telomerase-associated protein (TP1)-did not change during
      tamoxifen treatment, as revealed by RT-PCR analysis. Furthermore, the hTERT
      splice pattern was not shifted from the active full-length variant (+alpha/+beta)
      to the inactive deletion variants (-alpha; -beta; -alpha/-beta) and the level of
      the 120 kDa hTERT full-length protein remained constant, as shown by Western blot
      analysis. Protein kinase C (PKC) activity has been suggested to be crucial for
      post-translational up-regulation of telomerase activity. In HepG2 cells, we
      observed a tamoxifen-induced suppression of the total protein kinase C (PKC)
      activity (cytosolic and membrane-bound). Inhibition of PKC with
      bisindolylmaleimide I resulted in a reduction of telomerase activity, as revealed
      by TRAP-assay. Alpha-tocopherol (vitamin E) diminished the effects of tamoxifen
      on PKC-activity as well as on telomerase activity. CONCLUSIONS: We conclude that
      the tamoxifen-induced decrease of telomerase activity in HepG2 cells is mediated
      post-translationally via suppression of PKC-activity.

PMID- 15503140
TI  - Mismatch repair ensures fidelity of replication and recombination in the
      radioresistant organism Deinococcus radiodurans.
AB  - We have characterized the mismatch repair system (MMR) of the highly radiation
      resistant type strain of Deinococcus radiodurans, ATCC 13939. We show that the
      MMR system is functional in this organism, where it participates in ensuring the
      fidelity of DNA replication and recombination. The system relies on the activity
      of two key proteins, MutS1 and MutL, which constitute a conserved core involved
      in mismatch recognition. Inactivation of MutS1 or MutL resulted in a seven-fold
      increase in the frequency of spontaneous RifR mutagenesis and a ten-fold increase
      in the efficiency of integration of a donor point-mutation marker during
      bacterial transformation. Inactivation of the mismatch repair-associated UvrD
      helicase increased the level of spontaneous mutagenesis, but had no effect on
      marker integration--suggesting that binding of MutS1 and MutL proteins to a
      mismatched heteroduplex suffices to inhibit recombination between non identical
      (homeologous) DNAs. In contrast, inactivation of MutS2, encoded by the second
      mutS -related gene present in D. radiodurans, had no effect on mutagenesis or
      recombination. Cells devoid of MutS1 or MutL proteins were as resistant to gamma
      rays, mitomycin C and UV-irradiation as wild-type bacteria, suggesting that the
      mismatch repair system is not essential for the reconstitution of a functional
      genome after DNA damage.

PMID- 15503141
TI  - Gold color in onions (Allium cepa): a natural mutation of the chalcone isomerase
      gene resulting in a premature stop codon.
AB  - Unusual gold-colored onions were selected from a F3 family originating from a
      cross between US-type yellow and Brazilian yellow onions. HPLC analysis showed
      that the gold onions contained a significantly reduced amount of quercetin, the
      most abundant flavonoid in onions. This result indicated that an early step in
      the flavonoid biosynthesis pathway might be abnormal in these onions. The
      expression of flavonoid synthesis genes isolated from onions was examined in gold
      onions and compared to that in onions of other colors by RT-PCR. The results
      showed that all genes were transcribed in gold onions as in red onions. In order
      to identify any critical mutations in flavonoid synthesis genes encoding enzymes
      involved in early steps of the pathway, the genomic sequence of chalcone
      isomerase (CHI) was obtained. A premature stop codon and a subsequent single base
      pair addition causing a frameshift were identified in the coding region of the
      CHI gene in the gold onions. Co-segregation of the mutant allele of the CHI gene
      and the gold phenotype was investigated in the original F2 segregating
      population. Genotyping of three color groups (red, yellow and gold) of F2 onions
      revealed perfect co-segregation of the mutant CHI allele with the gold phenotype.
      All tested gold F2 onions were homozygous for the mutant CHI allele. This perfect
      co-segregation implies that the presence of a premature stop codon in the gold
      CHI gene results in an inactive CHI. Inactivation of CHI results in a block in
      the flavonoid biosynthesis pathway and the accumulation of chalcone derivatives,
      including a yellow pigment which might be responsible for the gold color in
      onions.

PMID- 15503142
TI  - Haplotype block and superblock structures of the alpha1-adrenergic receptor genes
      reveal echoes from the chromosomal past.
AB  - A significant proportion of the human genome is contained within haplotype blocks
      across which pairwise linkage disequilibrium (LD) is very high. However, LD is
      also often high between markers at more remote distances, and within different
      haplotype blocks. Here, we evaluate the origins of haplotype block structure in
      the three genes for alpha1 adrenergic receptors (alpha1-AR) in the human genome (
      ADRA1A, ADRA1B and ADRA1D) by genotyping dense single-nucleotide polymorphism
      (SNP) marker maps, and show that LD signals between distant markers are due to
      the presence of extended haplotype superblocks in individuals with ancient
      chromosomes which have escaped historic recombination. ARs mediate the
      physiological effects of epinephrine and norepinephrine, and are targets of many
      therapeutic drugs. This work has identified haplotype backgrounds of alpha1-AR
      missense variants, haplotype block structures in US Caucasians and African
      Americans, and haplotype tag SNPs for each block, and we present strong evidence
      for ancient haplotype block superstructure at these genes which has been
      partially disrupted by recombination, and evidence for reinstatement of linkage
      disequilibrium by subsequent recombination events. ADRA1A is comprised of four
      haplotype blocks in US Caucasians, while in African Americans Block 1 is split.
      ADRA1B has four blocks in US Caucasians, but in African Americans only the first
      two blocks are present. ADRA1D has two blocks in US Caucasians, and the first
      block is replaced by two smaller blocks in African Americans. For both ADRA1A and
      ADRA1B, haplotype superstructures may represent a novel, higher-level hierarchy
      in the human genome, which may reduce redundancy of testing by further
      aggregation of genotype data.

PMID- 15503143
TI  - The vicinity of a broken chromosome end affects P element mobilization in
      Drosophila melanogaster.
AB  - Broken chromosome ends are believed to be capped by a terminal protein complex,
      and can be maintained in Drosophila melanogaster for many generations. We
      investigated whether the vicinity of a chromosome end affected P element
      mobilization and the subsequent repair of the resulting DNA lesion. High levels
      of P element excision were observed when at least 5 kb of DNA was located between
      the P element and the end of the chromosome, but recovery of chromosomes from
      which the P element had been excised was greatly reduced when the chromosome end
      was positioned less than 5 kb away from the original P element insertion site.
      Moreover, when the P element was mobilized in terminal deficiency ( y (TD ))
      alleles, excision events were accompanied by deletions of sequences originally
      located distal to the P element.

PMID- 15503144
TI  - Genomic paleontology provides evidence for two distinct origins of Asian rice
      (Oryza sativa L.).
AB  - The origin of rice domestication has been the subject of debate for several
      decades. We have compared the transpositional history of 110 LTR retrotransposons
      in the genomes of two rice varieties, Nipponbare (Japonica type) and 93-11
      (Indica type) whose complete sequences have recently been released. Using a
      genomic paleontology approach, we estimate that these two genomes diverged from
      one another at least 200,000 years ago, i.e., at a time which is clearly older
      than the date of domestication of the crop (10,000 years ago, during the late
      Neolithic). In addition, we complement and confirm this first in silico analysis
      with a survey of insertion polymorphisms in a wide range of traditional rice
      varieties of both Indica and Japonica types. These experimental data provide
      additional evidence for the proposal that Indica and Japonica rice arose from two
      independent domestication events in Asia.

PMID- 15503145
TI  - Virulence regulators RfaH and YaeQ do not operate in the same pathway.
AB  - The expression of virulence factors such as hemolysin and lipopolysaccharides in
      Proteobacteria is regulated by the transcription elongation factor RfaH. RfaH
      reduces pausing and termination at intergenic sites, and thus allows RNA
      polymerase to conclude transcription of the distal genes in long virulence
      operons. The yaeQ gene of Salmonella enterica sv. Typhimurium has been identified
      as a high-copy-number suppressor of the hemolytic defect in an rfaH deletion
      strain, leading to speculation regarding a direct role of YaeQ in the
      transcriptional control of bacterial virulence. In order to evaluate this
      hypothesis, yaeQ genes from Escherichia coli and S. enterica sv. Typhimurium were
      cloned and expressed. Their products, purified YaeQ proteins, displayed no
      antitermination effects in in-vitro transcription assays over a wide range of
      concentrations, neither by themselves nor in competition with RfaH. When
      overexpressed in vivo, plasmid-borne E. coli and S. enterica sv. Typhimurium yaeQ
      genes also failed to restore hemolytic activity in an rfaH deletion strain under
      conditions in which episomal E. coli rfaH and its orthologs exhibited full
      complementation of the genomic rfaH deletion. Taken together, our findings do not
      support the hypothesis of YaeQ involvement in RfaH-dependent regulation of
      virulence, even in stoichiometric excess in vitro or upon overexpression in vivo.

PMID- 15503146
TI  - Y chromosome haplogroups of elite Ethiopian endurance runners.
AB  - Favourable genetic endowment has been proposed as part of the explanation for the
      success of East African endurance athletes, but no evidence has yet been
      presented. The Y chromosome haplogroup distribution of elite Ethiopian athletes
      (n=62) was compared with that of the general Ethiopian population (n=95) and a
      control group from Arsi (a region producing a disproportionate number of
      athletes; n=85). Athletes belonged to three groups: marathon runners (M; n=23), 5
      km to 10-km runners (5-10K; n=21) and other track and field athletes (TF; n=18).
      DNA was extracted from buccal swabs and haplogroups were assigned after the
      typing of binary markers in multiplexed minisequencing reactions. Frequency
      differences between groups were assessed by using contingency exact tests and
      showed that Y chromosome haplogroups are not distributed amongst elite Ethiopian
      endurance runners in the same proportions as in the general population, with
      statistically significant (P<0.05) differences being found in four of the
      individual haplogroups. The geographical origins and languages of the athletes
      and controls suggest that these differences are less likely to be a reflection of
      population structure and that Y chromosome haplogroups may play a significant
      role in determining Ethiopian endurance running success.

PMID- 15503147
TI  - Adult stemmata of the butterfly Vanessa cardui express UV and green opsin mRNAs.
AB  - Adult stemmata are distinctive insect photoreceptors located on the posterior
      surfaces of the optic lobes. They originate as larval eyes that migrate inward
      during metamorphosis. We used a combination of light microscopy and in situ
      hybridization to examine their anatomical organization in the butterfly Vanessa
      cardui and to test for the presence of visual pigments, the light sensitive
      components of the visual transduction pathway. The bilateral cluster of six
      internal stemmata is located near the ventral edge of the lamina. They retain the
      dark screening pigment and overlying crystalline cones of the larval stemmata. We
      found two opsin mRNAs expressed in the stemmata that are also expressed,
      respectively, in UV-sensitive and green-sensitive photoreceptor cells in the
      compound eye. A third mRNA that is expressed in blue-sensitive photoreceptor
      cells of the compound eye was not expressed in the stemmata. Our results
      reinforce the idea that the adult stemmata are not merely developmental remnants
      of larval eyes, but remain functional, possibly as components of the circadian
      input channel.

PMID- 15503148
TI  - Characteristics of cultured subepithelial fibroblasts in the rat small intestine.
      II. Localization and functional analysis of endothelin receptors and cell-shape
      independent gap junction permeability.
AB  - Subepithelial fibroblasts form a cellular network with gap junctions under the
      epithelium of the gastrointestinal tract. Previously, we have reported their
      unique characteristics, such as reversible rapid cell-shape changes from a flat
      to a stellate configuration induced by dBcAMP and endothelins (ETs), and Ca2+
      responses to, for example, ETs, ATP, and substance-P. We have now investigated
      the subtypes of ET receptors both in the rat small intestine and in primary
      cultured subepithelial fibroblasts isolated from rat duodenal villi. Their
      properties were compared between wild-type and endothelin-B-receptor-mutant sl/sl
      rats. Light- and electron-microscopic immunohistochemistry showed intense ETA
      immunoreactivity in the subepithelial fibroblasts from the small intestine and
      colon of both wild-type and sl/sl rats. In culture, immunocytochemistry, reverse
      transcription/polymerase chain reaction analysis, Ca2+ response measurements, and
      cell-shape change analysis indicated functional ETA and ETB receptors in the wild
      type cells, but only ETA in the sl/sl cells. However, wild-type cells were more
      sensitive to ET-1 than to ET-3 by about one order of magnitude. ETA seemed to be
      dominant both in vivo and in vitro. The relationship between cell-shape change
      and gap junction permeability was examined by fluorescence recovery after
      photobleaching; the gap junctions were usually open but were blocked by
      carbenoxolone. Permeability did not change significantly with cell-shape change.
      This network of differentiated subepithelial fibroblasts may maintain
      intercellular communication via gap junctions to transduce signals evoked in the
      local network to the whole network. The cell-shape change of the cells through
      ETA activation may play an important role as a barrier and for intercellular
      signaling in the intestinal villi.

PMID- 15503149
TI  - Involvement of interaction of ZP1 and ZPC in the formation of quail perivitelline
      membrane.
AB  - The extracellular matrix surrounding the oocyte before ovulation is called the
      perivitelline membrane (PL) in avian species. We have previously reported that
      one of its components, ZPC, is produced in ovarian granulosa cells by the
      stimulation of follicle-stimulating hormone and testosterone. Another component,
      ZP1, is synthesized in the liver and might be transported to the surface of the
      oocyte of the follicles. These glycoproteins are assembled to form a three
      dimensional network of coarse fibers between the granulosa cells and the oocyte.
      In the present study, we have evaluated the involvement of the interaction of ZPC
      and ZP1 in the formation of the PL of Japanese quail. By measuring the
      incorporation of tritium-labeled proteins into the PL, we have found that tritium
      labeled ZPC is specifically incorporated into the PL. Whole-mount
      autoradiographic analysis of the PL has also revealed the incorporation of the
      secreted ZPC into the isolated PL. To study which component in the PL is
      responsible for the specific incorporation of ZPC, PL lysates were incubated with
      the conditioned medium of the granulosa cells and were immunoprecipitated with
      anti-ZPC antiserum. Western blot analysis of the immunoprecipitated materials
      indicated that the 175-kDa and 97-kDa ZP1 forms were co-immunoprecipitated with
      anti-ZPC antiserum. These results demonstrate that ZPC secreted from the
      granulosa cells specifically binds with ZP1, and that the phenomenon might be
      involved in insoluble PL fiber formation in quail ovary.

PMID- 15503150
TI  - Midbrain-derived neural stem cells: from basic science to therapeutic approaches.
AB  - Neural stem cells (NSCs) are a subtype of tissue-specific progenitor cells
      capable of extended self-renewal and the ability to generate all major cell types
      of nervous tissue, such as neurons, astroglia and oligodendroglial cells. Recent
      studies suggest that salient patterning in anterior-posterior and dorsal-ventral
      axes occurs early, concomitantly with neural induction and therefore stem cells
      and restricted precursors exhibit regionalization. Fetal mesencephalic NSCs can
      be isolated and expanded in vitro for many months while retaining their potential
      to differentiate into glia and neurons, with a subset of neurons displaying all
      the major properties of mature functional dopaminergic neurons. Since Parkinson's
      disease (PD) is characterized by the loss of a specific type of dopaminergic
      cells, the prospect of replacing the missing or damaged cells is very attractive
      in PD. Thus, mesencephalic NSCs might serve as a new and continuous source of
      dopaminergic neurons for regenerative strategies in this neurodegenerative
      disorder. This review discusses new data concerning the cell biology and
      therapeutic potential of NSCs derived from the midbrain region of the central
      nervous system.

PMID- 15503151
TI  - Contrast enhancement: a physiological effect of striatal dopamine?
AB  - Dopamine functions as an important neuromodulator in the dorsal striatum and
      ventral striatum/nucleus accumbens. Evidence is accumulating for the idea that
      striatal neurons compete with each other for control over the animal's motor
      resources, and that dopamine plays an important modulatory role that allows a
      particular subset of neurons, encoding a specific behavior, to predominate in
      this competition. One means by which dopamine could facilitate selection among
      competing neurons is to enhance the contrast between stronger and weaker
      excitations (or to increase the "signal to noise ratio" among neurons, where the
      firing of the most excited neurons is assumed to transmit signal and the firing
      of the least excited to transmit noise). Here, we review the electrophysiological
      evidence for this hypothesis and discuss potential cellular mechanisms by which
      dopamine-mediated contrast enhancement could occur.

PMID- 15503152
TI  - Synucleins and their relationship to Parkinson's disease.
AB  - Parkinson's disease (PD) is one of the most common neurodegenerative motor
      disorders, marked by chronic progressive loss of neurons in the substantia nigra.
      It has long been believed that PD is caused by environmental factors. The
      discovery of genetic factors involved in PD has improved the understanding of the
      pathology of the disease. The first gene found to be mutated in PD encodes for
      the presynaptic protein alpha-synuclein. alpha-Synuclein is a major component of
      Lewy bodies and Lewy neurites, which represent the morphological hallmarks of the
      disease. The mechanisms by which alpha-synuclein is involved in nigral cell death
      remain poorly understood. Moreover, the factors triggering the formation of alpha
      synuclein-positive inclusion bodies remain enigmatic. Indeed, even the normal
      cellular functions of alpha-synuclein and of the other synucleins (beta-synuclein
      and gamma-synuclein) are still unknown. Several lines of evidence suggest that
      they play a role in the regulation of vesicular turnover under normal
      nonpathological conditions.

PMID- 15503153
TI  - Parkin-associated Parkinson's disease.
AB  - Mutations in the PARK2 gene coding for parkin cause autosomal recessive juvenile
      parkinsonism (AR-JP), a familial form of Parkinson's disease (PD). Parkin
      functions as an E3 ubiquitin ligase, and loss of this ubiquitin ligase activity
      appears to be the mechanism underlying pathogenesis of AR-JP. Recently, the
      spectrum of genetic, clinical, and pathological findings on AR-JP has been
      significantly expanded. Moreover, a considerable number of parkin interactors
      and/or substrates have been identified and characterized, and animal models of
      parkin deficiency have been generated. In this review, we provide an overview of
      the most relevant findings and discuss their implications for the pathogenesis of
      AR-JP and sporadic PD.

PMID- 15503154
TI  - Causes of Parkinson's disease: genetics of DJ-1.
AB  - The identification of Mendelian mutations in rare forms of familial Parkinson's
      disease (PD) have provided significant insights into the molecular pathogenesis
      of this common complex disorder. DJ-1 is the third of four genes known to be
      definitively causal in familial PD, the three others being alpha-synuclein,
      parkin and the recently identified PINK1. Mutations in the DJ-1 gene were
      identified in two European families, a Dutch kindred harbouring a large
      homozygous genomic deletion encompassing exons 1-5 of the gene and an Italian
      kindred with a homozygous L166P missense mutation. The clinical phenotype of the
      two families was similar to that of parkin cases. Age of onset was in the mid
      thirties with good responsiveness to l-dopa and slow disease progression. Focal
      dystonias and blepharospasm were also evident as were behavioural disturbances
      early in the course of the disease. To date, there are no studies of pathological
      material from known DJ-1 patients. It therefore remains to be determined whether
      these patients form Lewy bodies and/or Lewy neurites, the eosinophilic fibrillary
      inclusions that contain predominantly alpha-synuclein and that are the
      pathological hallmark of PD.

PMID- 15503155
TI  - Classic toxin-induced animal models of Parkinson's disease: 6-OHDA and MPTP.
AB  - Neurological disorders in humans can be modeled in animals using standardized
      procedures that recreate specific pathogenic events and their behavioral
      outcomes. The development of animal models of Parkinson's disease (PD) is
      important to test new neuroprotective agents and strategies. Such animal models
      of PD have to mimic, at least partially, a Parkinson-like pathology and should
      reproduce specific features of the human disease. PD is characterized by massive
      degeneration of dopaminergic neurons in the substantia nigra, the loss of
      striatal dopaminergic fibers and a dramatic reduction of the striatal dopamine
      levels. The formation of cytoplasmic inclusion bodies (Lewy bodies) in surviving
      dopaminergic neurons represents the most important neuropathological feature of
      PD. Furthermore, the massive striatal dopamine deficiency causes easily
      detectable motor deficits in PD patients, including bradykinesia, rigidity, and
      resting tremor, which are the cardinal symptoms of PD. Over the years, a broad
      variety of experimental models of PD were developed and applied in diverse
      species. This review focuses on the two most common "classical" toxin-induced PD
      models, the 6-hydroxy-dopamine (6-OHDA model) and the 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) model. Both neurotoxins selectively and rapidly destroy
      catecholaminergic neurons, whereas in humans the PD pathogenesis follows a
      progressive course over decades. This discrepancy reflects one important and
      principal point of weakness related to most animal models. This review discusses
      the most important properties of 6-OHDA and MPTP, their modes of administration,
      and critically examines advantages and limitations of selected animal models. The
      new genetic and environmental toxin models of PD (e.show $132#g. rotenone,
      paraquat, maneb) are discussed elsewhere in this "special issue."

PMID- 15503156
TI  - Damaging effect of the fish pathogen Aeromonas salmonicida ssp. salmonicida on
      intestinal enterocytes of Atlantic salmon (Salmo salar L.).
AB  - In fish, bacterial pathogens can enter the host by one or more of three different
      routes: (a) skin, (b) gills and (c) gastrointestinal tract. Bacteria can cross
      the gastrointestinal lining in three different ways. In undamaged tissue,
      bacteria can translocate by transcellular or paracellular routes. Alternatively,
      bacteria can damage the intestinal lining with extracellular enzymes or toxins
      before entering. Using an in vitro (Ussing chamber) model, this paper describes
      intestinal cell damage in Atlantic salmon (Salmo salar L.) caused by the fish
      pathogen Aeromonas salmonicida ssp. salmonicida, the causative agent of
      furunculosis. The in vitro method clearly demonstrated substantial detachment of
      enterocytes from anterior region of the intestine (foregut) upon exposure to the
      pathogen. In the hindgut (posterior part of the intestine), little detachment was
      observed but cellular damage involved microvilli, desmosomes and tight junctions.
      Based on these findings, we suggest that A. salmonicida may obtain entry to the
      fish by seriously damaging the intestinal lining. Translocation of bacteria
      through the foregut (rather than the hindgut) is a more likely infection route
      for A. salmonicida infections in Atlantic salmon.

PMID- 15503157
TI  - Hyaluronidase expression in cultured growth plate chondrocytes during
      differentiation.
AB  - Hyaluronan (HA) is a major component of the extracellular matrix of cartilage,
      contributes to its structural and functional integrity, and has various important
      roles in the differentiation of chondrocytes. HA metabolism is regulated by both
      anabolic and catabolic processes; however, the details have not yet been
      clarified. The purpose of this study was to clarify the expression patterns of
      hyaluronidase (HAase) mRNAs (from the relevant HAase genes: the HYALs) and HAase
      activity during chondrocyte differentiation. Cartilage tissue and growth plate
      chondrocytes were isolated from the ribs of 4-week-old male Japanese rabbits. The
      expression of HYAL mRNAs in cartilage was analyzed by in situ hybridization. The
      expression levels of HYAL mRNAs in the culture were analyzed for each of the
      chondrocyte differentiation stages by means of quantitative real-time polymerase
      chain reaction analysis. Enzymatic activity in the conditioned medium from the
      cultures was examined by using HA zymography and an enzyme-linked immunosorbent
      like assay. The expression levels of HYAL1 and HYAL2 mRNAs were enhanced about
      2.8-fold and 3.2-fold at the maximum during the early matrix forming stage,
      respectively, and by about 3.2-fold and 2.0-fold at the maximum in the
      hypertrophic stage, respectively. HYAL3 mRNA was not detected throughout the
      experimental period. HAase activity was enhanced at the early matrix forming and
      hypertrophic stages. These results suggest that selective expression of HYALs is
      essential for extracellular HA metabolism during chondrocyte differentiation.

PMID- 15503158
TI  - Reconstituted type V collagen fibrils as cementing materials in the formation of
      cell clumps in culture.
AB  - Previous studies have reported that type V collagen is an anti-adhesive substrate
      for cultured cells in that the cells detach from culture dishes coated with type
      V collagen molecules or polypeptides derived from them. We have noticed that
      human fetal lung fibroblasts (TIG-1) initially show no reduction in adherence to
      and spreading on a dish coated with reconstituted type V collagen fibrils but
      eventually detach from the dish and form cell clumps. To determine the way in
      which reconstituted type V collagen fibrils are involved in cell clump formation,
      we have followed the fate of the fluorescence of type V collagen fibrils pre
      labeled with fluorescein isothiocyanate. Essentially, all the fluorescence
      disappeared from the dish surface as the cells detached and was condensed in the
      cell clumps. The cells that were recovered from clumps and dissociated into
      separate cells by trypsin treatment proliferated normally after they were seeded
      on a bare culture dish. This result and those from gel electrophoresis,
      fluorescence microscopy, and a cell proliferation assay indicate that the cell
      detachment from the dish is not caused by cell necrosis or apoptosis but by
      cellular motility together with the unique features of type V collagen fibrils.
      Not only the adherence of type V collagen fibrils to TIG-1 cells is much stronger
      than that to the culture dish, but the fibrils are retained on the cellular
      surface. The strong adherence of type V collagen fibrils to cells plays a role in
      cementing TIG-1 cells together.

PMID- 15503159
TI  - Rat sperm AS-A: subcellular localization in testis and epididymis and surface
      distribution in epididymal sperm.
AB  - In this study, we investigated the subcellular compartmentalization of
      arylsulfatase-A (AS-A) in the testis and epididymis as well as the surface
      distribution in rat epididymal sperm. Testicular AS-A was compartmentalized
      specifically to the area underneath the outer acrosomal membrane of the acrosomal
      granule and to the dorsal aspect of the sperm acrosome. Epididymal AS-A was
      synthesized in the endoplasmic reticular (ER) network of principal cells and
      secreted into epididymal lumen as evident by its reactivity in the apical
      cytoplasm and vesicles therein underneath stereocilia. In clear cells, AS-A
      reactivity was found throughout the cytoplasmic machineries involved in
      endocytosis. Surface distribution of AS-A was initially detectable at the concave
      ridge as early as in sperm of the initial segment (IS). AS-A was additionally
      localized to the post-acrosomal region in caput (CP), corpus (CO) and cauda (CD)
      epididymal sperm. The expression levels of surface AS-A gradually increased
      during sperm transit from IS to CD epididymidis. These results favored the
      adsorption of AS-A from epididymal fluid onto the sperm surface, rather than
      shunting from the acrosome as a consequence of capacitation-associated membrane
      priming.

PMID- 15503160
TI  - Estrogenic stimulation of ovarian follicular maturation in diabetes (db/db)
      mutant mice: restoration of euglycemia prevents hyperlipidemic cytoatrophy.
AB  - The diabetes (db/db) mutation (leptin-receptor defect) induces a hyperglycemic
      hyperinsulinemic endometabolic environment that promotes hypercytolipidemic
      ovarian involution in C57BL/KsJ mice, resulting in reproductive sterility and
      eventual organoatrophy. The effectiveness of low-dose (1.0 microg/sc/3.5 day
      intervals), 17- beta-estradiol therapy (E2-HRx), initiated prior to expression of
      the overt diabetes-obesity syndrome (DOS), on preventing female ovarian
      follicular cytolipid atrophy was evaluated by analysis of cytochemical,
      endocrine, and tissue lipo-metabolic indices relative to oil-vehicle treated
      control (+/?) and (db/db) groups. Chronic low-dose E2-HRx moderated DOS-induced
      trends in (db/db) groups, maintaining lowered body weights, and systemic
      euglycemia while stimulating ovarian weight indices. E2-HRx prevented the
      dramatic hypercytolipidemic condition associated with ovarian follicular
      involution in (db/db) mice, as evidenced by progressive viable follicular
      maturation, cytomorphometric analysis of tertiary follicular development, and pre
      luteinization indices with diminished follicular atresia rates. The coincident
      stimulation of tissue lipoprotein lipase and acetyl CoA carboxylase activities in
      (db/db) ovarian compartments, under persistent hyperinsulinemic influences,
      indicated that E2-HRx effectively moderated both the structural and
      hyperlipometabolic consequences of DOS from promoting (db/db)-associated
      reproductive organoatrophy. Thus, the patho-reproductive alterations induced by
      the (db/db) mutation can be moderated through low-dose steroidal therapy, the
      efficacy of which is suspected to occur by steroid-specific nuclear transcription
      or post-insulin receptor modulation of gluco-metabolic cascades in reproductive
      target cells.

PMID- 15503161
TI  - Circatidal variation in epithelial cell proliferation in the mussel digestive
      gland and stomach.
AB  - Epithelial cell renewal in mussel ( Mytilus galloprovincialis, Lmk) digestive
      gland and stomach was investigated by bromodeoxyuridine (BrdU)
      immunohistochemistry. Mussels were exposed to 4 mg BrdU/l seawater continuously.
      Starting at 6 h after treatment, samples were collected every 2 h for 2 days and
      BrdU labelling was estimated by direct counting at the light microscope, with
      values being noted per thousand BrdU-positive cells. BrdU-positive reaction was
      observed in the nuclei of digestive, basophilic, duct and stomach cells, and in
      haemocytes. Cell renewal in digestive diverticula was synchronised following a
      circatidal pattern: BrdU labelling increased during low tide and decreased during
      high tide. Clearcut mitotic figures were identified in digestive cells, thereby
      confirming that mature cell types proliferate, in agreement with results from
      immunohistochemistry for proliferating cell nuclear antigen and BrdU. Epithelial
      cell renewal in the stomach also appeared to be synchronised.

PMID- 15503162
TI  - Parasite biodiversity and host defenses: chewing lice and immune response of
      their avian hosts.
AB  - Antagonistic host-parasite interactions lead to coevolution of host defenses and
      parasite virulence. Such adaptation by parasites to host defenses may occur to
      the detriment of the ability of parasites to exploit alternative hosts, causing
      parasite specialization and speciation. We investigated the relationship between
      level of anti-parasite defense in hosts and taxonomic richness of two chewing
      louse suborders (Phthiraptera: Amblycera, Ischnocera) on birds. While Amblyceran
      lice tend to occur in contact with host skin, feed on host skin and chew emerging
      tips of developing feathers to obtain blood, Ischnoceran lice live on feathers
      and feed on the non-living keratin of feather barbules. We hypothesized that
      Amblyceran abundance and richness would have evolved in response to interaction
      with the immune system of the host, while Ischnoceran taxonomic richness would
      have evolved independently of immunological constraints. In an interspecific
      comparison, the abundance of Ischnocerans was positively related to host body
      size, while host body mass and Ischnoceran taxonomic richness accounted for the
      abundance of Amblycerans. Amblyceran taxonomic richness was predicted by the
      intensity of T-cell mediated immune response of nestling hosts, while the T-cell
      response of adults had no significant effect. In contrast, Ischnoceran taxonomic
      richness was not predicted by host T-cell responses. These results suggest that
      the taxonomic richness of different parasite taxa is influenced by different host
      defenses, and they are consistent with the hypothesis that increasing host
      allocation to immune defense increases Amblyceran biodiversity.

PMID- 15503163
TI  - Light-dependent changes in the relationship between seed mass and seedling
      traits: a meta-analysis for rain forest tree species.
AB  - Seed mass is considered to be an important attribute for the establishment
      success of plant species being linked with their seed production, establishment,
      and survival. This meta-analysis shows that seed mass is also closely correlated
      to growth-related species attributes of the established phase of rain forest tree
      species, and that the strength of this relationship varies with light conditions.
      Seed mass is an especially good predictor of species traits under high-light
      conditions, when the species attain their full growth potential. At high
      irradiance (>20% of full light) seed mass is negatively correlated with RGR, NAR,
      LAR, SLA and LMF. At low irradiance (<5% of full light), seed mass is only
      negatively correlated with LAR and SLA. Correlations between seed mass and
      morphological traits are therefore strongest at low irradiance where light
      interception is important. Conversely, correlations between seed mass and a
      physiological trait are strongest at high irradiance, where maximization of
      photosynthetic rates is important. The strength of the correlation between growth
      parameters and seed mass declines over time, and disappears after 1-4 years. Seed
      mass appears to be a good proxy for the shade tolerance of tropical tree species,
      especially at the younger stages of the life cycle.

PMID- 15503164
TI  - Ecological stoichiometry of ants in a New World rain forest.
AB  - C:N stoichiometry was investigated in relation to diet (delta(15)N), N
      deprivation, and worker body size for a diverse assemblage of tropical Amazonian
      ants. Relative nitrogen (N) deprivation was assayed for 54 species as an exchange
      ratio (ER), defined as SUCmin/AAmin, or the minimum sucrose concentration,
      divided by the minimum amino acid concentration, accepted as food by >/=50% of
      tested workers. On average, N-deprivation (ER) was almost fivefold greater for N
      omnivorous and N-herbivorous (N-OH) taxa than for N-carnivores. In two-way ANOVAs
      at three taxonomic levels (species and species groups, genera, and tribes),
      higher ER was associated with small body size and (marginally) with less
      carnivorous diets. ERs did not differ systematically between trophobiont-tending
      and "leaf-foraging" functional groups, but specialized wound-feeders and coccid
      tenders were prominent among high ER taxa. Paradoxically, some high ER taxa were
      among the most predatory members of their genera or subfamilies. Biomass % N was
      lower in N-OH taxa than in carnivores and varied inversely with N-deprivation
      (log ER) in the former taxa only. In an expanded data set, N-content increased
      allometrically in N-OHs, N-carnivores, and all ants combined, and with carnivory
      in large-bodied ants only. Exceptional taxa included small-bodied and predaceous
      Wasmannia, with high % N despite high ER, and Linepithema, with the lowest % N
      despite high delta(15)N. Patterns in C:N stoichiometry are explained largely at
      the genus level and above by elemental composition of alarm/defensive/offensive
      chemical weaponry and, perhaps in some cases, by reduced N investment in cuticle
      in taxa with high surface:volume ratios. Several consequences of C:N
      stoichiometry identify Azteca, and possibly Crematogaster, as taxa preadapted for
      their roles as prominent associates of myrmecophytes. C:N stoichiometry of ants
      should be incorporated into models of strategic colony design and examined in a
      phylogenetic context as opportunities permit.

PMID- 15503165
TI  - Limitations on reproductive success in endemic Aquilegia viscosa (Ranunculaceae)
      relative to its widespread congener Aquilegia vulgaris: the interplay of
      herbivory and pollination.
AB  - Plant reproduction can be strongly affected by herbivory and different features
      of pollination ecology, such as pollinator visitation rates and capacity for self
      pollination. The purpose of this study is to compare the relative impact of
      herbivory and pollination on maternal reproductive success in endemic Aquilegia
      viscosa and its widespread congener Aquilegia vulgaris. We conducted herbivore
      exclusion experiments in two populations of each species in 2 different years and
      showed that the maternal fertility of A. viscosa was significantly more limited
      by floral predation and pre-dispersal seed predation than its widespread
      congener. In the absence of herbivory, A. viscosa retained significantly lower
      maternal fertility than A. vulgaris. Experimental pollinations in an insect-free
      glasshouse showed that the two species have an equal seed/ovule ratio both in the
      absence of pollinators and in the presence of non-limiting outcross pollination.
      Pollinator visitation rates were significantly higher in populations of A.
      vulgaris than in populations of A. viscosa. In addition, path analyses showed
      that spur length, an important trait for pollinator attraction in Aquilegia, and,
      indirectly sepal and petal width, contribute positively to the seed/ovule ratio
      in A. vulgaris, but not in A. viscosa. These results indicate that maternal
      fertility of endemic A. viscosa is strongly reduced by flower and seed predation
      despite low rates of pollinator visitation, and that pollen or resource
      limitation in the wild may further reduce maternal fertility. Finally, floral
      trait variation appears to be decoupled from fertility variation in endemic A.
      viscosa, which possibly constrains the evolution of reproductive traits in this
      species.

PMID- 15503166
TI  - Oviposition site selection in a complex and variable environment: the role of
      habitat quality and conspecific cues.
AB  - In many organisms reproductive success is strongly dependent on several breeding
      site characteristics, which often vary in space and time. Although we have a good
      understanding of how ovipositing organisms respond to single factors, we still
      have little information about how they respond under more complex natural
      conditions. We examined the oviposition behavior of a tree-hole breeding frog,
      Phrynobatrachus guineensis, with respect to abiotic and biotic oviposition site
      characteristics, including desiccation risk and the presence of conspecific
      offspring using both observation and experiments. Based on daily monitoring data,
      compiled from 69 natural oviposition sites during a complete reproductive season,
      we developed oviposition site-selection models. A model based on water presence,
      sediment depth and maximal possible water depth showed the best predictive
      performance and was transferable to the subsequent season. Field observations and
      experiments revealed that frogs could estimate water-holding capacity of sites
      and timed oviposition with respect to future water presence. Despite the negative
      effects on larval growth and the availability of sites without conspecifics, data
      suggest that ovipositing individuals are attracted to conspecific offspring
      because they serve as a cue for low predation risk. Our results imply that a
      site's potential for being used at least once for oviposition was determined by
      abiotic factors, whereas the relative use of breeding sites was determined by a
      response to conspecifics. Our study demonstrates the importance of including
      multiple biotic and abiotic factors in the analysis of oviposition site
      selection.

PMID- 15503167
TI  - Genetic forms of nephrotic syndrome.
AB  - Mutations of NPHS1, NPHS2, or WT1 may be responsible for severe forms of
      nephrotic syndrome in children, progressing to end-stage renal failure. Recent
      studies have shown that congenital nephrotic syndrome may be secondary to
      mutations of one of these three genes and that some patients have a digenic
      inheritance of NPHS1 and NPHS2 mutations. The clinical spectrum of NPHS2
      mutations has broadened, with the demonstration that mutations in the respective
      gene podocin may be responsible for nephrotic syndrome occurring at birth, in
      childhood, or in adulthood. It is now well recognized that podocin mutations are
      found in 10%-30% of sporadic cases of steroid-resistant nephrotic syndrome with
      focal segmental glomerulosclerosis. Data from large cohorts indicate that the
      risk of recurrence of nephrotic syndrome after renal transplantation in patients
      with podocin mutations is very low.

PMID- 15503169
TI  - Percutaneous treatment of transplant renal artery stenosis in children.
AB  - Percutaneous treatment of renal artery stenosis (RAS) is an accepted procedure
      and numerous reports have been published. However, experience with its use in RAS
      in the transplanted kidney in children is scarce. Since 1994 we have diagnosed
      RAS in seven children with the use of Doppler ultrasonography (US), confirming it
      with percutaneous angiography (PAG). In six of the seven patients percutaneous
      transluminal angioplasty (PTA) was performed. In one patient a metallic stent was
      placed due to the extension of the arterial lesion, and a second stent was placed
      in another child when a re-stenosis was diagnosed 1 month after the PTA. All
      patients presented with hypertension (de novo or 30% increase over previous
      values). After ruling out acute rejection, calcineurin inhibitor toxicity, and
      urinary obstruction, US was performed and, when an increase in arterial flux
      velocity was registered, PAG was also performed. Six children showed an increase
      in serum creatinine (Cr) and proteinuria. Blood pressure decreased after the
      procedure and Cr returned to previous levels in all children. One of the grafts
      was lost due to chronic transplant rejection 7 years later. The other children
      have a functioning kidney. Although this is a small group of patients, the
      consistently good results and the lack of reported experience prompted us to
      communicate our preliminary observation.

PMID- 15503170
TI  - Henoch Schonlein nephritis: clinical findings related to renal function and
      morphology.
AB  - We evaluated the renal hemodynamics and the urine protein excretion rates of 73
      children with Henoch-Schonlein nephritis (HSN). In 40 children we also performed
      a renal biopsy. The glomerular filtration rate (GFR) and effective renal plasma
      flow were determined by the clearances of inulin and para-aminohippurate during
      water diuresis. Urine albumin and IgG excretion were assessed in short-term timed
      samples. The mean GFR at the first examination was reduced in the HSN patients
      and most reduced in those with nephrotic proteinuria. There was an inverse
      correlation between the GFR at the first examination and the amount of
      albuminuria and urinary IgG excretion. Among the 40 patients with some degree of
      proteinuria who underwent a renal biopsy, 9 of 13 patients with mild to moderate
      proteinuria had severe morphological changes. GFR correlated inversely and
      fractional albumin and IgG excretion directly with the severity of the
      pathological findings on the biopsy, and with segmental and global sclerosis, the
      grade of mesangial proliferation, and interstitial inflammation. In conclusion,
      GFR is moderately reduced early in HSN and more reduced in patients with more
      proteinuria and in those with more advanced morphological changes. Moreover, even
      mild to moderate proteinuria may indicate severe morphological changes, which
      increase the indications for early renal biopsy in these patients.

PMID- 15503171
TI  - A WT1 exon 1 mutation in a child diagnosed with Denys-Drash syndrome.
AB  - Denys-Drash syndrome (DDS) is characterized by nephropathy, genital
      abnormalities, and predisposition to Wilms tumor. DDS is associated with
      constitutional WT1 mutations, the majority being missense mutations in the zinc
      finger region. A dominant-negative mode of action of the mutant DDS proteins is
      thought to explain the more severe genitourinary phenotype seen in DDS compared
      with children with complete deletion of one WT1 allele. We present a
      phenotypically female child who presented with bilateral Wilms tumor at 8 months
      of age. She was found to have an XY karyotype and diagnosed with DDS. In the
      constitutional DNA of this child we found a previously unreported mutation in
      exon 1 of WT1. This de novo mutation, delT in codon 40, is predicted to produce a
      termination signal in codon 90 (F40fsX90). This frameshift mutation results in a
      severely truncated protein, which would remove both the zinc-finger DNA-binding
      domain and the majority of the N-terminal regulatory domain, including regions
      previously shown in vitro to be necessary for inhibition of WT1 transcriptional
      activity. Our results provide important physiological evidence that the first 40
      amino acids of WT1 are capable of functionally important interactions, presumably
      through their ability to self-associate with full-length WT1.

PMID- 15503172
TI  - Hyponatremic-hypertensive syndrome with extensive and reversible renal defects.
AB  - Two young children with renal artery stenosis and severe hypertension who
      presented with the so-called hyponatremic-hypertensive syndrome (HHS), with
      marked urine and solute loss during the acute phase, are described. Both children
      also presented with severe high molecular proteinuria, glycosuria, and
      hypercalciuria, only the first symptom having prompt remission after
      normalization of blood pressure. In children with renal artery stenosis, HHS is
      associated with severe proteinuria due to hyperfiltration and more extensive
      tubular functional alterations. Hyponatremia and acute tubulopathy may mask the
      presenting clinical picture of renal artery stenosis.

PMID- 15503173
TI  - Mizoribine oral pulse therapy for steroid-dependent nephrotic syndrome.
AB  - There have been reports of the use of mizoribine (MZB) oral pulse therapy for the
      treatment of systemic lupus erythematosus. We report its efficacy in a 9-year-old
      girl with steroid- and cyclosporine-dependent nephrotic syndrome (NS). The
      patient experienced relapses of NS when prednisolone was tapered to 20 mg/day
      after discontinuing cyclosporine due to biopsy proven toxicity. When
      methylprednisolone pulse therapy combined with prednisolone therapy (40 mg/day)
      failed to result in a complete remission after 3 weeks, oral MZB pulse therapy
      (total dose of 500 mg, 10 mg/kg per day in three divided daily doses twice a
      week) was given. This therapy was continued for 9 months and resulted in complete
      remission of the NS for 6 months despite the discontinuation of prednisolone. The
      serum concentration of MZB was above 2.5 microg/ml for about 10 h (from 3 h after
      the first dose of MZB to 2 h after the final dose). Thus, our results suggest
      that this regimen may be effective for patients with steroid-dependent NS.

PMID- 15503174
TI  - Evolution of acute focal bacterial nephritis into a renal abscess.
AB  - Acute focal bacterial nephritis (AFBN) is a localized bacterial infection of the
      kidney presenting as an inflammatory mass without frank abscess formation, which
      may represent a relatively early stage of renal abscess. The pathogenesis of AFBN
      is thought to be hematogenous infection or ascending infection from the lower
      urinary tract. For the majority of children, the pathogenesis may be related to
      ascending infection, because pre-existing malformative uropathy, especially
      vesicoureteral reflux (VUR), is common in pediatric patients. Few clinical
      reports have demonstrated the evolution of this condition into renal abscess in
      children. We report a girl with AFBN associated with VUR that evolved into a
      renal abscess despite appropriate intravenous antibiotic therapy. We undertook
      serial radiological observation of its evolution. It is important to
      differentiate AFBN from renal abscess because the management of the two entities
      may be different, and follow-up studies are indispensable to determine
      appropriate therapy.

PMID- 15503175
TI  - Glomerulonephritis in a patient with chronic active Epstein-Barr virus infection.
AB  - Renal involvement is rare in chronic active Epstein-Barr virus (EBV) infection.
      We report an 11-year-old girl who had focal mesangial proliferative
      glomerulonephritis with cellular crescents and renal tubular atrophy with foam
      cells in the lumen at the time of the first admission. However, the patient was
      not diagnosed with chronic active EBV infection until the third admission, 18
      months later, because she did not exhibit typical clinical manifestations of
      infectious mononucleosis, i.e., fever, lymphadenopathy, hepatomegaly, or
      increased atypical lymphocytes. We performed in situ hybridization of EBV in
      renal biopsy and renal autopsy tissue and found EBV genome-positive cells in the
      enlarged vascular areas surrounding the renal tubules in both specimens. The
      relationship between mesangial proliferative glomerulonephitis with crescents and
      chronic active EBV infection is unknown.

PMID- 15503176
TI  - Hemolytic uremic syndrome associated with Clostridium difficile colitis.

PMID- 15503177
TI  - Pore size and charge selectivity of the glomerular membrane at the time of
      diagnosis of diabetes.
AB  - The urinary albumin excretion rate is increased at the time of diagnosis of
      diabetes. We investigated whether this is caused by change in pore size or charge
      selectivity in the glomerular basement membrane. Urine excretion of
      immunoglobulins (IgG2, IgG4), glycosaminoglycans (GAG), and albumin was analyzed
      during the first 20 days after diagnosis of diabetes in children aged 4-15 years;
      36 diabetic and 24 age-matched apparently healthy children were included. The
      excretion of albumin was significantly increased on day 1 in the diabetic
      children. Between day 1 and 20 the excretion of IgG2 and IgG4 decreased
      significantly from normal to a level below normal. GAG excretion was not
      affected. The GAG/creatinine index (GAGCI) was normal. IgG2CI was significantly
      below normal on days 4-20. IgG4CI was below normal on days 2-20. The albumin
      creatinine index decreased significantly from day 1 to normal levels on day 4-20.
      A charge selectivity index, expressed as the ratio between the neutrally charged
      IgG2 and the negatively charged IgG4, was significantly below the normal level on
      days 16 and 20. In conclusion, an increased albumin excretion rate in urine did
      not seem to be caused by a change in charge selectivity. Other explanations such
      as change in the small pore radius or tubular reabsorption are suggested.

PMID- 15503178
TI  - Acidosis increases magnesiuria in children with distal renal tubular acidosis.
AB  - In experimental animals, metabolic acidosis increases renal magnesium (Mg)
      excretion, whereas metabolic alkalosis reduces it. The objective of this study
      was to examine renal magnesium handling (U(Mg)) in children with primary distal
      renal tubular acidosis (DRTA). We measured U(Mg) in 11 children (3 females, 8
      males, aged 6.9+/-4.9 years) with primary DRTA. They were studied either during
      spontaneous acidosis post treatment removal (3 patients) or after ammonium
      chloride (100 mmol/m2) induced acidosis (8 patients), and then following oral
      sodium bicarbonate load (4 g/1.73 m2). During acidosis (plasma pH 7.28+/-0.09,
      bicarbonate 13.2+/-4.3 mEq/l), U(Mg) was elevated (U(Mg/Cr) 0.18+/-0.06 mg/mg,
      normal values 0.1+/-0.06, P=0.003) although plasma Mg (P(Mg)) was in the normal
      range (1.93+/-0.31 mg/dl, controls 1.77+/-0.19, P=NS). After acute correction of
      metabolic acidosis (plasma pH 7.44+/-0.05, bicarbonate 25.6+/-1.6 mEq/l, P<0.001;
      urine pH 7.52+/-0.28, bicarbonate 86.9+/-39.1 mEq/l), U(Mg) decreased
      significantly (P=0.003), returning to control values after about 2 h (U(Mg/Cr)
      0.09+/-0.06 mg/mg). Bicarbonate load resulted not only in reduction in U(Mg) but
      also in a decrease in urinary calcium excretion (U(Ca/Cr)) from 0.46+/-0.17 mg/mg
      to 0.14+/-0.12 mg/mg (P<0.001). We conclude that in children with primary DRTA,
      urinary Mg excretion is markedly increased and that this defect, like the
      hypercalciuric defect, is correctable by sodium bicarbonate administration.

PMID- 15503179
TI  - Unusual cause of peritonitis during peritoneal dialysis. Rhodotorula rubra and
      amphotericin B.

PMID- 15503180
TI  - Urinary cystatin C as a marker of GFR? A word of caution.

PMID- 15503181
TI  - Immunization in children with chronic renal failure: a practical approach.
AB  - The prevention of systemic viral and bacterial infections by effective
      vaccination represents an essential task of pediatric nephrologists caring for
      children with chronic renal failure (CRF) undergoing renal transplantation (RTPL)
      with life-long immunosuppression. This review addresses three issues: risk of
      vaccine-preventable diseases, safety, immunogenicity, and clinical efficacy of
      available vaccines, and implementation of immunization guidelines. Infections
      (including vaccine-preventable infections) represent the leading cause of
      morbidity and mortality in children on dialysis and after RTPL. Vaccination in
      children with CRF and after RTPL is safe and does not cause reactivation of an
      immune-related renal disease or rejection after RTPL. Children with CRF generally
      produce protective serum antibodies to primary vaccinations with killed or
      component vaccines and live virus vaccines; some children on dialysis and after
      RTPL may not respond optimally, requiring repeated vaccination. Proof of vaccine
      efficacy is absence of disease, which can only be confirmed in large cohort
      studies. A few observational studies provide evidence that vaccination has
      contributed significantly, at least in the western hemisphere, to the low
      prevalence of vaccine-preventable diseases among children with CRF. Close
      cooperation between the local pediatrician/practitioner and the pediatric
      nephrologist is essential for successful implementation of the vaccination
      schedule.

PMID- 15503182
TI  - Body mass index in primary and secondary pediatric hypertension.
AB  - The objectives of this study were (1) to determine the relationship of body mass
      index (BMI) to primary or secondary hypertension in children and adolescents and
      (2) to assess BMI at the age of onset of hypertension in children and
      adolescents. Patient demographics, BMI, family history, presentation of disease,
      etiology of hypertension, medication, laboratory data, and findings from other
      procedures were recorded for all patients with hypertension followed in the
      Pediatric Nephrology Clinic at Children's Hospital, Columbus, Ohio, over a 4-year
      period. In total, 314 patients were studied: 218 with primary hypertension and 96
      with secondary hypertension. Our patient population (166 males, 148 females) was
      diverse in age (13+/-6.3 years) and ethnicity (237 Caucasians, 54 African
      Americans, 23 other). BMI was greater in patients with primary (27.5+/-9.2 kg/m2)
      versus secondary (23.9+/-9.3 kg/m2) hypertension (P=0.002). Children with primary
      hypertension with an increased BMI presented at an earlier age than children with
      secondary hypertension and an increased BMI. The age of onset (10.5+/-2.6 years)
      in primary hypertension was related to increased BMI (r=0.12, P=0.001); however,
      there was no relationship between BMI and age of onset of secondary hypertension
      (P=0.21). Children whose family members had essential hypertension had increased
      BMI compared with children without a family history of essential hypertension.
      Based on the logistic regression model constructed from our data, the likelihood
      of primary versus secondary hypertension was influenced by the presence of family
      history of hypertension independent of presence of obesity in the child. In
      conclusion, increased BMI is more common in children with primary than secondary
      hypertension; earlier onset of primary hypertension in the pediatric population
      was associated with increased BMI; the assessment of BMI is important in the
      evaluation of secondary as well as primary hypertension; the role of obesity in
      the development of secondary as well as primary hypertension in children merits
      further study.

PMID- 15503183
TI  - Determination of urinary bicarbonate with the Henderson-Hasselbalch equation.
      Comparison using two different methods.
AB  - The determination of urinary bicarbonate with the Henderson-Hasselbalch equation
      was compared using two methods: (1) correcting the pK in every urine sample
      according to ionic strength and using the solubility constant of CO2 in urine
      (alpha=0.0309) and (2) using a fixed pK value (6.1) and a CO2 solubility constant
      of 0.0301, which we use to calculate blood bicarbonate. Nine patients were
      studied and 29 determinations were performed. A high correlation was found
      between the methods (r=0.99). Bicarbonate calculated with corrected pK was 24.3+/
      6.6 mEq/l (95% confidence interval 11.4-37.2) and bicarbonate calculated with pK
      fixed at 6.1 was 25.6+/-6.6 mEq/l (95% confidence interval 12.7-38.5). For each
      urine sample, the delta bicarbonate was calculated as the difference between the
      bicarbonate obtained with pK at 6.1 minus that obtained with the corrected pK
      (mean 1.25, standard error 0.83, P=0.15). This indicates that the difference
      between the methods was not significant. No difference was found whether pK was
      corrected or fixed (6.1). Therefore, our results suggest that it is valid to take
      the value shown by the equipment for blood gas determination as the urinary
      bicarbonate value. This would allow the rapid and accurate determination of
      urinary bicarbonate in patients with hyperchloremic acidosis, especially those
      with renal tubular acidosis.

PMID- 15503184
TI  - Transport of airborne pollen into the city of Thessaloniki: the effects of wind
      direction, speed and persistence.
AB  - We examined the effect of the wind vector analyzed into its three components
      (direction, speed and persistence), on the circulation of pollen from different
      plant taxa prominent in the Thessaloniki area for a 4-year period (1996-1999).
      These plant taxa were Ambrosia spp., Artemisia spp., Chenopodiaceae, Corylus
      spp., Cupressaceae, Olea europaea, Pinaceae, Platanus spp., Poaceae, Populus
      spp., Quercus spp., and Urticaceae. Airborne pollen of Cupressaceae, Urticaceae,
      Quercus spp. and O. europaea make up approximately 70% of the total average
      annual pollen counts. The set of data that we worked with represented days
      without precipitation and time intervals during which winds blew from the same
      direction for at least 4 consecutive hours. We did this in order to study the
      effect of the different wind components independently of precipitation, and to
      avoid secondary effects produced by pollen resuspension phenomena. Factorial
      regression analysis among the summed bi-hourly pollen counts for each taxon and
      the values of wind speed and persistence per wind direction gave significant
      results in 22 cases (combinations of plant taxa and wind directions). The pollen
      concentrations of all taxa correlated significantly with at least one of the
      three wind components. In seven out of the 22 taxon-wind direction combinations,
      the pollen counts correlated positively with wind persistence, whereas this was
      the case for only two of the taxon-wind speed combinations. In seven cases,
      pollen counts correlated with the interaction effect of wind speed and
      persistence. This shows the importance of wind persistence in pollen transport,
      particularly when weak winds prevail for a considerable part of the year, as is
      the case for Thessaloniki. Medium/long-distance pollen transport was evidenced
      for Olea (NW, SW directions), Corylus (NW, SW), Poaceae (SW) and Populus (NW).

PMID- 15503185
TI  - A.B. Frank and mycorrhizae: the challenge to evolutionary and ecologic theory.
AB  - A. B. Frank's observations and hypotheses about mycorrhizae in 1885 flew in the
      face of conventional thinking of the time. He reported that what we now term
      ectomycorrhizae were widespread on root systems of many woody plant species in a
      great diversity of habitats and soils. He hypothesized that mycorrhizae represent
      a pervasive mutualistic symbiosis in which fungus and host nutritionally rely on
      each other; that the fungus extracts nutrients from both mineral soil and humus
      and translocates them to the tree host; and that the tree, in turn, nourishes the
      fungus. Initially opposed by much of the scientific community, nearly all of
      Frank's major hypotheses have since been unequivocally demonstrated, although
      many decades were required to achieve conclusive evidence. Nonetheless, the
      revolution in thinking about plant and fungal evolution, ecology and physiology
      generated by Frank is still in the process of acceptance by much of the
      scientific community, 120 years and tens of thousands of scientific papers since
      he coined the term "mycorrhiza". The reasons for this extraordinary lag time in
      themselves present an intriguing research subject.

PMID- 15503186
TI  - Arbuscular mycorrhizal colonization of the dominant plant species in primary
      successional volcanic deserts on the Southeast slope of Mount Fuji.
AB  - Arbuscular mycorrhizal (AM) colonization was observed on four plant species in
      primary successional volcanic deserts on the Southeast slope of Mount Fuji. The
      AM colonization of the dominant species, Polygonum cuspidatum, contradicts the
      conclusion that Polygonaceae are often regarded as being non-mycorrhizal species.
      The secondary dominant species, Polygonum weyrichii var. alpinum, formed no
      mycorrhizas. The roots of Cirsium purpuratum, Clematis stans and Campanula
      punctata ssp. hondoensis, showed a higher percentage of AM colonization than P.
      cuspidatum. AM colonization and spore density in the rhizosphere soil of P.
      cuspidatum significantly decreased as elevation increased. AM colonization in
      roots of Cirsium purpuratum and Clematis stans also tended to decrease with
      increased altitudes. Cirsium purpuratum and Campanula punctata ssp. hondoensis
      formed single structural types of Arum- and Paris-type, respectively, whereas P.
      cuspidatum and Clematis stans formed both Arum- and Paris-type morphologies.

PMID- 15503187
TI  - Chemical alteration of the rhizosphere of the mycorrhizal-colonized wheat root.
AB  - Plexiglass pot growth chamber experiments were conducted to evaluate the chemical
      alterations in the rhizosphere of mycorrhizal wheat roots after inoculation with
      Glomus intraradices [arbuscular mycorrhizal fungus (AMF)]. Exchange resins were
      used as sinks for nutrients to determine whether the inoculated plant can
      increase the solubility and the uptake of P and micronutrients. Treatments
      included: (1) soil (bulk soil); (2) AMF inoculation no P addition (I-P); (3) no
      inoculation with no P addition (NI-P); (4) AMF inoculation with addition of 50 mg
      P (kg soil)(-1) (I+P), and (5) no inoculation with addition of 50 mg P (kg soil)(
      1) (NI+P). The AMF inoculum was added at a rate of four spores of G. intraradices
      (g soil)(-1). The exchange resin membranes were inserted vertically 5 cm apart in
      the middle of Plexiglass pots. Spring wheat (Triticum aestivum cv. Len) was
      planted in each Plexiglass pot and grown for 2 weeks in a growth chamber where
      water was maintained at field capacity. Rhizosphere pH and redox potential (Eh),
      nutrient bioavailability indices and mycorrhizal colonization were determined.
      Mycorrhizal inoculation increased the colonization more when P was not added, but
      did not increase the shoot dry weight at either P level. The rhizosphere pH was
      lower in the inoculated plants compared to the noninoculated plants in the
      absence of added P, while the Eh did not change. The decrease in pH in the
      rhizosphere of inoculated plants could be responsible for the increased P and Zn
      uptake observed with inoculation. In contrast, Mn uptake was decreased by
      inoculation. The resin-adsorbed P was increased by inoculation, which, along with
      the bioavailability index data, may indicate that mycorrhizal roots were able to
      increase the solubility of soil P.

PMID- 15503188
TI  - Early changes in pulmonary function following thoracotomy for scoliosis
      correction: the effect of size of incision.
AB  - It is generally believed that minimal access surgery may produce less change in
      pulmonary function than conventional open thoracotomy for scoliosis correction.
      Though there is considerable literature regarding changes in pulmonary function
      tests (PFT) after thoracotomy, there is scant data available regarding the effect
      of the magnitude of thoracic wall disruption on pulmonary function, particularly
      in the early postoperative weeks. This study aims to evaluate the effect of the
      size of incision on pulmonary function after anterior release and fusion in
      patients with moderate thoracic curves due to adolescent idiopathic scoliosis.
      The study group was made up of 19 patients with thoracic curves due to adolescent
      idiopathic scoliosis. The subjects had had thoracotomy for anterior release,
      followed by posterior instrumentation and fusion at a second sitting. The ten
      patients who had had conventional, large thoracotomy were placed in group A and
      the nine minimal access cases in group B. PFTs consisting of volume (FVC) and
      flow (FEV1) were obtained before the anterior release, 2 weeks later (before the
      posterior instrumented fusion), and 3 months after the posterior fusion. The
      degree of deformity in the sagittal and the coronal plane preoperatively and
      postoperatively were measured and documented. The mean preoperative pulmonary
      function was significantly less than the predicted values for both patient
      groups. There was a decline in the postoperative pulmonary function (both
      percentage predicted value and absolute value) in both groups at 2 weeks and at 3
      months. The deterioration of pulmonary function was less in the small-thoracotomy
      group, but this difference between the groups was statistically significant only
      for the 2-week values. Our study shows that there is significant pulmonary
      function restriction even in patients with moderate thoracic curves. There was a
      lesser decline in pulmonary function in the minimal-access group, as compared
      with the standard thoracotomy group, but this difference was only in the early
      postoperative period and became insignificant by 3 months.

PMID- 15503189
TI  - Giant intracerebral choroid plexus calcification.
AB  - While small calcifications of the choroid plexus are frequent, a large, single
      intracerebral calcification originating from the choroid plexus is rare. This
      report presents a 27-year-old woman who was admitted because of right temporal
      headache which had persisted for months. There was no neurological deficit.
      Computed tomography demonstrated a mass of calcium density measuring
      approximately 3 x 3 x 4 cm in the right temporal region, extending to the
      temporal skull base and to the rostral edge of the petrous bone. At surgery a
      very hard, poorly vascularised tumour originating from the choroid plexus of the
      temporal horn of the right lateral ventricle was completely removed. Histological
      workup yielded the diagnosis of a markedly calcified choroid plexus with no
      indication of neoplasia or inflammation. Physiological intracranial
      calcifications resulting from local tissue dystrophy are usually incidental. In
      the case presented here, a large intracerebral choroid plexus calcification was
      detected in a patient presenting with episodes of severe headache. The potential
      pathogenetic mechanism is discussed.

PMID- 15503190
TI  - Pituitary apoplexy following laparascopic cholocystectomy.

PMID- 15503194
TI  - Inhibition of microglial activation by the herbal flavonoid baicalein attenuates
      inflammation-mediated degeneration of dopaminergic neurons.
AB  - Accumulating evidence has suggested that inflammation in the brain participates
      in the pathogenesis of Parkinson's disease (PD). Therefore, anti-inflammatory
      therapy has attracted much attention as novel interference to neurodegenerative
      diseases. Baicalein, a major flavonoid extracted from a traditional Chinese herb
      Scutellaria baicalensis Georgi (Huangqin), possesses potent anti-inflammatory and
      antioxidant properties. To test the potential neuroprotective effect of baicalein
      on dopaminergic neurons, primary midbrain neuron-glia cultures from E-14 rat
      embryos were used. Cultures were pretreated with baicalein for 30 min prior to
      stimulation with lipopolysaccharide (LPS, 10 ng/ml). LPS leads to massive
      activation of microglial cells revealed by OX-42 immunostaining, and produced
      excessive quantities of NO. Excessive elevation of superoxide level was also
      observed in enriched-microglia after stimulating with LPS. LPS-induced damage to
      dopaminergic neurons was evaluated by uptake capacity for [3H]dopamine and
      tyrosine hydroxylase (TH)-immunocytochemistry. Pretreatment with baicalein
      concentration-dependently attenuated LPS-induced decrease in [3H]dopamine uptake
      and loss of TH-immunoreactive (TH-ir) neurons, which the maximum protective
      effect was observed at the concentration of 5 microM. Post-treatment with
      baicalein (5 microM) was also shown to be effective even if baicalein
      administered up to 2 h later than LPS application. Morphological study shows that
      baicalein (5 microM) almost completely blocked LPS-induced activation of
      microglia. Excessive production of TNF(alpha) and free radicals such as NO and
      superoxide by LPS stimulation were also attenuated by baicalein at a
      concentration-dependent pattern. The present study indicates that baicalein
      exerts potent neuroprotective effect on LPS-induced injury of dopaminergic
      neurons. We hypothesize that the inhibition of LPS-induced production of NO and
      free radicals from microglia may underlie the mechanism of baicalein's
      neuroprotection.

PMID- 15503195
TI  - Effects of riluzole on combined MPTP + 3-nitropropionic acid-induced mild to
      moderate striatonigral degeneration in mice.
AB  - We investigated the potency of riluzole, an anti-glutamatergic drug, to affect
      ongoing neuronal death process following combined MPTP + 3-nitropropionic acid (3
      NP) intoxication producing combined striatal and nigral degeneration (SND) in
      mice. We used a "neuronal rescue" strategy by administering riluzole after the
      end of intoxication. The motor disorder, its recovery, behavioral performances at
      motor and sensorimotor integration tasks and histopathological outcome were
      compared in the saline and riluzole groups (10 mg/kg and 20 mg/kg), matched by
      triplets for motor severity. While riluzole did not produce any effect on the
      gross motor disorder nor on rotarod task, open-field kinetic variables or on the
      traversing beam task, it had a subtle effect on the performances at the pole
      test. The histopathological outcome was significantly better in the riluzole
      treated mice regarding both nigral and dorsolateral striatal cell loss and
      astroglial activation, with a dose-effect relationship. Thus, riluzole has
      limited "neuronal rescue" properties from an histopathological point of view with
      a subtle motor behavior improvement in a MPTP + 3-NP-induced SND in mice.

PMID- 15503196
TI  - The yield of laboratory investigations in children with infantile autism.
AB  - PURPOSE: To evaluate the yield of laboratory investigations in infantile autism.
      METHODS: We retrieved and evaluated the results of investigative procedures
      recorded in the medical files of autistic infants in four child developmental
      centers and two pediatric psychiatric outpatient clinics. RESULTS: One-hundred
      and thirty-two infants were included in the study of whom 47 (36%) underwent
      autistic regression at an average age of 20 months. The investigative procedures
      included electroencephalogram (n = 132), neuroimaging (n = 70), genetic studies
      to detect Fragile-X (n = 59) and a metabolic workup (n = 53). Except for the
      molecular diagnosis that revealed Fragile-X syndrome in two children (3%), all
      other tests were negative. The two infants with the Fragile-X syndrome belonged
      to the non-regressive group. CONCLUSIONS: The only investigative study that
      contributed to the diagnosis of autistic infants was the molecular diagnosis
      detecting Fragile-X. In spite of the high frequency of epilepsy and epileptiform
      abnormalities in the electroencephalograms of autistic children in general, the
      contribution of epilepsy, both clinical and subclinical, to the etiology of
      autism is apparently minimal.

PMID- 15503197
TI  - An open-label evaluation of the tolerability and safety of Stalevo (carbidopa,
      levodopa and entacapone) in Parkinson's disease patients experiencing wearing
      off.
AB  - OBJECTIVES: To evaluate the tolerability, safety and efficacy of Stalevo
      (carbidopa, levodopa and entacapone) in Parkinson's disease (PD). BACKGROUND:
      Levodopa provides the most effective symptom control for the treatment of
      Parkinson's disease (PD). However, its long-term use is limited by the
      development of motor complications such as wearing-off. Catechol-O
      methyltransferase (COMT) inhibitors such as entacapone extend the plasma half
      life of levodopa and reduce 'off' time. Stalevo is a new levodopa product that
      combines carbidopa, levodopa and entacapone in one tablet. Clinical studies have
      not been reported with this compound. DESIGN METHODS: An open-label, multi-center
      US trial evaluated 169 consecutive PD patients experiencing end-of-dose wearing
      off, with (n = 39) and without (n = 130) mild dyskinesia. Patients were switched
      from immediate-release carbidopa/levodopa to Stalevo and were treated for four
      weeks. Assessments included tolerability measures, adverse events profile, the
      disease-specific quality of life instrument PDQ-39, UPDRS parts II, III, and
      question 39 and investigator and patient global clinical assessments. RESULTS: 14
      subjects (8%) discontinued treatment with Stalevo, of which 12 (7%) were due to
      adverse events. 11/130 (8.5%) subjects developed new onset dyskinesia and 17/39
      (43.6%) of patients with existing dyskinesia reported a worsening in their
      dyskinesia. However, this was managed by a change in dose in 21.4% of patients
      and in another 10.7% dyskinesias resolved without any need for dose adjustment.
      Other side effects were infrequent and mild, the most common being nausea (12.4%)
      dizziness (6.5%) and somnolence (6.5%). Stalevo treatment resulted in significant
      improvements in PDQ-39 and UPDRS (II + III) scores (p < 0.001). Assessment of
      'off' time demonstrated a reduction in off time in 32% of patients, compared with
      an increase in 7% of patients. Improvements were noted by both investigator
      (68.1%) and patient (68.6%) assessments. CONCLUSIONS: Switching PD patients
      experiencing wearing-off from carbidopa/levodopa therapy to Stalevo was safe,
      well tolerated and resulted in clinical improvement.

PMID- 15503198
TI  - Induction of MHC-I and thymic depletion due to replication of JEV in mouse brain.
AB  - The thymus is a primary lymphoid organ that is responsible for T cell development
      and maturation. Thymic depletion accompanied by apoptosis and altered T cell
      maturation occurs during several viral infections. Here we show that adult mice
      intracerebrally infected with Japanese encephalitis virus exhibit severe cell
      depletion and alterations in the CD4(+) and CD8(+) single as well as CD4(+)CD8(+)
      double positive cell populations. A 5.6 fold induction of MHC-I but not MHC-II
      was observed on thymocytes of such mice and was accompanied with a progressive
      depletion of thymocytes as the disease progressed with 90% of double positives
      being depleted by 9 days post infection. Staining studies with propidium iodide
      and Annexin V revealed that the percent thymocytes undergoing apoptosis had
      increased significantly in animals infected with Japanese encephalitis virus.
      Although similar changes in MHC-I expression were also observed in newborn pups
      challenged with Japanese encephalitis virus, qualitative and quantitative
      differences in thymocyte depletion were observed relative to the adult thymus.
      These observations may have implications in the ability of the immune system to
      respond to specific antigens and possible autoimmunity in survivors of Japanese
      encephalitis infection.

PMID- 15503199
TI  - Co-infection of Staphylococcus aureus or Haemophilus paragallinarum exacerbates
      H9N2 influenza A virus infection in chickens.
AB  - H9N2 influenza viruses are frequently isolated from chicken meat and bone marrow
      imported from China to Japan since 2001. These isolates were experimentally
      inoculated into specific pathogen-free chickens intranasally. Viruses were
      recovered from the meat and bone marrow of birds showing no overt signs. On the
      other hand, chickens co-infected with H9N2 virus and either Staphylococcus aureus
      or Haemophilus paragallinarum showed clinical signs severer than those shown by
      birds infected only with the virus alone or each of the bacteria alone. In
      addition, H9N2 viruses were more efficiently recovered from the chickens co
      infected with S. aureus or H. paragallinarum than those from the birds infected
      with only the virus. The present results indicate that co-infection of H9N2
      influenza virus with S. aureus or H. paragallinarum enhances the replication of
      the virus in chickens, resulting in exacerbation of the H9N2 virus infection.

PMID- 15503200
TI  - Pattern of N gene-mediated systemic hypersensitive response and turnover of viral
      replicase protein in tobacco.
AB  - We examined the pattern of the N gene-mediated systemic hypersensitive response
      (HR), which was induced by tobacco mosaic virus upon temperature shift, and
      analyzed the distribution of the coat protein and the virus-encoded 126 kDa
      replicase protein (126 K protein) by immunoblot analysis. In the middle- and
      lower-positioned leaves, HR occurred in the advancing edge of the infected area,
      where we detected both the coat protein and the 126 K protein. In the areas
      between the main vein and the advancing edge of these leaves, we observed no HR
      and did not detect 126 K protein, though virus was present in these areas. In the
      upper-positioned mosaic leaves, patterns of the HR were different depending on
      the leaf age. In these mosaic leaves, the mechanism preventing the virus from
      invading dark green tissue seemed to be broken down in 8-14 days old leaves, and
      HR was observed only in the tissue just invaded by the virus, where we detected
      the 126 K protein. Those results suggested that the viral 126 K protein was
      present when the viral replication was taking place, and easily degraded when the
      amount of the virus was saturated in the cells.

PMID- 15503201
TI  - Molecular epidemiology of hepatitis B, C and D viruses in Turkish patients.
AB  - Different genotypes of the hepatitis viruses may influence the clinical outcome
      of the disease. The distribution of genotypes may vary according to geographical
      regions. The aim of this study was to evaluate hepatitis B virus (HBV), hepatitis
      C virus (HCV) and hepatitis D virus (HDV) genotypes in Turkish patients with
      chronic hepatitis in a large cohort of patients. Genotyping was performed in 41,
      59 and 365 patients with chronic hepatitis B, D and C, respectively, and 36
      hemodialysis patients with chronic hepatitis C. Genotypes were determined by
      direct sequencing in hepatitis B and by polymerase chain reaction-restriction
      fragment length polymorphism in hepatitis C and D patients. In addition, HBV
      subtyping by multiplex PCR and subtype specific ELISA were performed in 83 and 71
      HBsAg (+) blood donors, respectively. All hepatitis B (100%) and hepatitis D
      (100%) patients had genotype D and type I, respectively. HBsAg subtyping by two
      methods yielded that 99% of the patients were subtype ayw. S gene amino acid
      sequence in the 41 patients included for HBV genotyping revealed the ayw2
      subtype. Genotype distribution of 365 patients with chronic C hepatitis were as
      follows: 306 (84%) patients genotype 1b, 43 (11%) patients genotype 1a, 10 (3%)
      patients genotype 2, 3 (1%) patients genotype 3, 3 (1%) patients genotype 4.
      Among 36 patients receiving hemodialysis, 28 (78%) patients had genotype 1b and 8
      (22%) patients had genotype 1a. The study indicates that Turkish patients with
      chronic viral hepatitis show very little genotypic heterogeneity. Subtype ayw and
      the genotype D of HBV DNA, and the type I of HDV RNA represent almost 100% of
      related infections. The genotype 1b of HCV RNA was found to be significantly
      dominant in Turkish patients.

PMID- 15503202
TI  - Specificity of neuraminidase activity from influenza viruses isolated in
      different hosts tested with novel substrates.
AB  - Influenza A and B viruses isolated in Vero and Madin Darby canine kidney (MDCK)
      cells as well as in fertilised hen eggs were tested for the specificity of their
      neuraminidase (NA) activity. Novel glycoconjugates with variations of terminally
      bound sialic acid mimicking the three main receptor types for influenza viruses
      were synthesised. These new substrates together with the lectin from Ricinus
      communis were used in a solid phase microtitre assay for the detection of NA
      specificity. Egg or MDCK isolated virus strains tended to exhibit highest NA
      activity against 3'sialyl-bound sialic acid whereas Vero isolated strains
      favoured 6'sialyl-(N-acetyllactosamine)-bound sialic acid. Differences were more
      pronounced for influenza A than for influenza B strains.

PMID- 15503203
TI  - A new potato virus in a new lineage of picorna-like viruses.
AB  - On constructing a cDNA library for potato, 'contaminating' sequences with a
      significant identity to Apple latent spherical virus (ALSV) were found.
      Determination of the remaining genome sequence indicated the presence of a
      bipartite virus with an RNA1 and 2 of 7034 and 3315 nucleotides, respectively,
      excluding a poly(A)tail. RNA1 encodes a single polyprotein (233 kDa) and shares
      highest amino acid identity with ALSV at 65%. Conserved amino acid motifs typical
      for helicase, protease and RNA-dependent polymerase (RdRp) functions are present.
      RNA2 encodes a single polyprotein (106 kDa) with amino acid identities to the
      flat apple isolate of Cherry rasp leaf virus (CRLV-FA) (97%) and ALSV (70%),
      suggesting this is a potato strain of CRLV (CRLV-pot). Phylogenetic analysis
      using the RdRp region shows that this virus falls within a group separate from
      the Comoviridae that includes members of the Sequiviridae and the taxonomically
      unassigned viruses ALSV, Strawberry mottle virus, Satsuma dwarf virus and Navel
      orange infectious mottling virus. Other regions of the genome have highest
      identities with both plant and animal infecting members of the picorna-like virus
      superfamily. The evolutionary context of CRLV-pot and related viruses is
      discussed. Similar viral sequences from an EST library of peppermint are also
      analysed.

PMID- 15503204
TI  - A sandwich-ELISA for the diagnosis of Peste des petits ruminants (PPR) infection
      in small ruminants using anti-nucleocapsid protein monoclonal antibody.
AB  - A sandwich ELISA test using PPR specific monoclonal antibody (clone 4G6) to an
      epitope of nucleocapsid protein has been developed. The test uses polyclonal sera
      to capture the antigen from clinical samples (swabs and tissues). Captured
      antigens from clinical samples are detected using PPR specific monoclonal
      antibody. The test is specific to PPR as it failed to detect rinderpest vaccine
      virus (RBOK strain). Varieties of clinical samples originating from laboratory
      experiments (n = 231) and from field (n = 259) were employed to test the efficacy
      of sandwich-ELISA test. The test compared very well with an internationally
      accepted commercial Immune-capture ELISA kit, which uses biotinylated monoclonal
      antibody against the nucleocapsid protein. On a parallel testing using 490
      clinical samples, 4G6 MAb based sandwich ELISA had an overall relative diagnostic
      specificity of 92.8% and diagnostic sensitivity of 88.9% compared to the
      commercial kit. The newly developed test is free from prozone phenomenon. PPR
      outbreaks from various parts of India have been confirmed using the test.
      Findings suggested that the newly developed ELISA is suitable for PPR diagnosis
      under field conditions.

PMID- 15503205
TI  - Susceptibility of Borna disease virus to the antiviral action of gamma
      interferon: evidence for species-specific differences.
AB  - Borna disease virus (BDV) infection in its predominant natural host - horses and
      sheep - leads to fatal meningoencephalomyelitis. The immune-mediated disease can
      also be induced experimentally in rats following intra- cerebral BDV infection.
      Despite a vigorous immune response, BDV persists in the central nervous system
      (CNS) in surviving rats. However, immunization of rats with BDV-specific T-cells
      prior to challenge with BDV prevents neurological disease and results in virus
      clearance from the CNS. To analyze whether interferon gamma (IFNgamma) might
      contribute to viral clearance in the rat brain, we tested the susceptibility of
      BDV to the antiviral action of rat IFNgamma using different rat cell lines. Even
      at high concentrations of IFNgamma, BDV infection of astrocyte and fibroblast
      cell lines as well as of rat embryo cells could not be inhibited efficiently.
      Similarly, infection of cultured rat hippocampal slices with BDV was not
      inhibited by rat IFNgamma. In contrast, de novo BDV infection of monkey kidney
      cells as well as human oligodendroglial cells was blocked by preincubation with
      human IFNgamma. Furthermore, IFNgamma reduced the BDV load in persistently BDV
      infected human oligodendroglial cells but not in infected rat astrocytes. These
      data suggest species-specific differences in the susceptibility of BDV to the
      antiviral action of IFNgamma.

PMID- 15503206
TI  - Ha-VP39 binding to actin and the influence of F-actin on assembly of progeny
      virions.
AB  - We present evidence that actin is necessary for the successful assembly of HaNPV
      virions. Purified nucleocapsid protein Ha-VP39 of Heliothis armigera nuclear
      polyhedrosis virus (HaNPV) was found to be able to bind to actin in vitro without
      assistance, as demonstrated by Western blot and isothermal titration calorimeter.
      DeltaH and binding constants (K) detected by isothermal titration calorimeter
      strongly suggested that Ha-VP39 first binds actin to seed the formation of
      hexamer complex of actin, and the hexamers then link to each other to form
      filaments, and the filaments finally twist into cable structures. The
      proliferation of HaNPV was completely inhibited in Hz-AM1 cells cultivated in the
      medium containing 0.5 microg/ml cytochalasin D (CD) to prevent polymerization of
      actin, while its yield was reduced to 10(-4) in the presence of 0.1 microg/ml CD.
      Actin concentration and the viral DNA synthesis were not significantly affected
      by CD even though the progeny virions assembled in the CD treated cells were
      morphologically different from normal ones and resulted in fewer plaques in
      plaque assay.

PMID- 15503207
TI  - Genetic analysis of the M RNA segment of Crimean-Congo hemorrhagic fever virus
      strains involved in the recent outbreaks in Russia.
AB  - Crimean-Congo hemorrhagic fever (CCHF) is a severe zoonosis with a high fatality
      rate. In Russia, local CCHF outbreaks have occurred in the Stavropol Territory,
      and the Volgograd and Astrakhan Regions during 2000 and 2001. Seven strains of
      CCHF virus (CCHFV) were isolated from infected patients and collected ticks. Two
      fragments of the CCHF virus M genome segment were PCR amplified and their
      nucleotide sequences were determined. All these virus strains appear to be
      closely related (up to 5.8% nucleotide sequence differences) and form a distinct
      clade on the CCHFV phylogenetic tree. Within this clade, CCHFV strains from
      Stavropol and Astrakhan cluster together, whereas those from Volgograd form a
      separate subgroup.

PMID- 15503208
TI  - CD14-mediated alterations in transcription and splicing of endogenous
      retroviruses after injury.
AB  - Increase in systemic levels of lipopolysaccharide (LPS) contributes to the
      pathogenesis of distant organ injury after burn. Stress signals elicited from
      burn influence transcriptional activities of mouse endogenous retroviruses
      (MuERVs) in various distant organs. The involvement of LPS pathways in the burn
      mediated regulation of MuERVs in the spleen was investigated in this study.
      Spleen harbors substantial numbers of tissue macrophages, a key responder to LPS
      stimulation. Spleen tissues collected from CD14 (LPS receptor) knockout (KO) and
      wild type (WT) mice after burn were subjected to RT-PCR analysis of MuERV
      expression. There was a substantial induction of 2 bands and a marked
      downregulation of a band in CD14 KO mice compared to WT mice after burn. Sequence
      analysis of these CD14- and burn-dependent bands identified 3 new alternatively
      spliced and 2 defective env transcripts of MuERVs as well as novel splicing
      signals. Chromosomal loci of putative MuERVs sharing the unique U3 sequences of
      these transcripts were mapped by surveying the entire genome of C57BL/6J mice. In
      addition, coding potentials, transcriptional regulatory elements, and adjacent
      cellular genes of these putative MuERVs were analyzed. The results from these
      studies suggest that injury-triggered LPS/CD14 signaling events play roles in the
      transcriptional regulation of certain MuERVs carrying unique U3 promoter
      sequences.

PMID- 15503209
TI  - Perforin knockout mice, but not mice with MAIDS, show protection against
      experimental cytomegalovirus retinitis after adoptive transfer of immune cells
      with a functional perforin cytotoxic pathway.
AB  - Adoptive transfer studies were performed to test the hypothesis that the perforin
      cytotoxic pathway is more important than the Fas/FasL cytotoxic pathway in
      protection against experimental murine cytomegalovirus (MCMV) retinitis. Splenic
      immune cells from donor MCMV-immunized normal mice or gld mice deficient in
      Fas/FasL-mediated cytotoxicity significantly reduced the frequency and severity
      of MCMV retinitis following subretinal MCMV challenge when transferred into
      recipient PKO mice deficient in perforin-mediated cytotoxicity. In sharp
      contrast, splenic cells from donor MCMV-immunized PKO mice failed to provide
      protection against MCMV retinitis when transferred into recipient PKO mice.
      Protection was not achieved, however, in recipient mice with retrovirus-induced
      immunodeficiency (MAIDS), even when splenic cells originated from MCMV-immunized
      normal mice.

PMID- 15503210
TI  - VP1, the RNA-dependent RNA polymerase and genome-linked protein of infectious
      bursal disease virus, interacts with the carboxy-terminal domain of translational
      eukaryotic initiation factor 4AII.
AB  - Infectious bursal disease virus (IBDV), a member of the family Birnaviridae, is a
      non-enveloped, double-stranded RNA virus. Viral protein 1 (VP1), the putative RNA
      dependent RNA polymerase, occurs in virions both as a free polypeptide and as a
      genome-linked protein, called VPg. To gain more insight in its function, we
      initiated a yeast two-hybrid screen. With this approach we identified the carboxy
      terminal domain of eukaryotic translation initiation factor 4AII (eIF4AII) as an
      interactor for VP1. The association between these molecules was confirmed by co
      immunoprecipitation analyses. eIF4A plays an essential role in the initiation of
      translation of both capped and uncapped mRNAs. Its association with IBDV VP1
      suggests an involvement of this viral protein in IBDV mRNA translation. An
      interaction between VP1 and full-length eIF4AII was, however, not observed. In
      view of the known two-domain structure of eIF4AII it is conceivable that the
      interaction of VP1 with full-length eIF4AII requires collaborating proteins that
      open up its structure and expose the VP1-binding site in the carboxy-terminal
      domain. The biological relevance of the potential VP1-eIF4AII interaction is
      discussed.

PMID- 15503211
TI  - A novel antigenic variant of Canine parvovirus from a Vietnamese dog.
AB  - Nine isolates of Canine parvovirus (CPV) were obtained from Vietnamese dogs and
      cats. One canine isolate showed a unique antigenic property which indicates a
      novel antigenic variant of CPV-2b when examined with hemagglutination inhibition
      tests using our monoclonal antibodies, 21C3 and 19D7, which were recently
      developed. This isolate had an amino acid substitution of residue 426, Asp to
      Glu, and the same substitution has recently been found in CPV from Italian dogs.
      This study first showed that such substitution caused an antigenic difference
      demonstrable by monoclonal antibodies and that a similar evolution may have
      occurred in CPV in Vietnam.

PMID- 15503212
TI  - Antigenically relevant amino acid positions as revealed by reactions of
      monoclonal antibodies with the nucleoproteins of closely related influenza A
      virus strains.
AB  - The nucleoproteins (NP) of a group of influenza A virus strains were analyzed
      with the use of a panel of anti-NP monoclonal antibodies (Mabs) in the
      radioimmunosorbtion reaction with subsequent polyacrylamide gel electrophoresis
      of the immune complexes, and in the immunoblotting. The group included 2 pairs of
      closely related viruses having minimal amino acid differences in NP sequence. The
      analysis of the results of the immune reactions in comparison with the known
      amino acid sequences of NP allowed us to suggest that the Mab 150/4 recognizes
      the epitope containing amino acid residues in positions 196 and/or 290, whereas
      the amino acid residue in position 353 participates in the formation of the
      antigenic epitope reacting with the Mab 7/3.

PMID- 15503213
TI  - Complete sequence of the RNA2 of an isolate of White clover cryptic virus 1, type
      species of the genus Alphacryptovirus.

PMID- 15503214
TI  - Complete sequence of the RNA1 of an isolate of White clover cryptic virus 1, type
      species of the genus Alphacryptovirus.

PMID- 15503215
TI  - 3C-like protease encoded by Rice tungro spherical virus is autocatalytically
      processed.
AB  - The 3C-protease of Rice tungro spherical virus (RTSV) was previously identified
      as a cis- and trans-acting protease. In vitro translation of the protease
      resulted in several protein products, demonstrating that the protease is cleaved
      by itself. The protease was then produced in Escherichia coli as a fusion protein
      with maltose-binding protein (MBP). Two forms of the protease were purified after
      MBP affinity chromatography in the column buffer. After analyses of the purified
      proteins, we speculated that a major internal cleavage site was in the C-terminal
      half. A point mutation was introduced at a potential major self-cleavage site
      (C(2763)). The mutation abolished the catalytic activity, suggesting that the
      mutation site is important for the recognition of the protease.

PMID- 15503216
TI  - The E5 protein of the human papillomavirus type 16 modulates composition and
      dynamics of membrane lipids in keratinocytes.
AB  - The E5 protein of the human papillomavirus type 16 is a small protein found
      associated to membranes, mainly in the Golgi apparatus, and expressed in the
      early stages of viral infection. Its expression modifies the cell response
      towards growth factors and stress exposures, and also blocks the surface
      expression of MHC molecules. A global explanation for these multiple effects is
      hitherto not available. Here we present data showing that the expression of HPV16
      E5 increases the amount of free cholesterol readily extractable from the plasma
      membrane, without altering the total cholesterol content. In addition, HPV16-E5
      modifies the composition of the cell membranes, increasing the synthesis rate of
      phosphatidylcholine and phosphatidylserine, while diminishing that of
      phosphatidylglycerol. We propose that these changes in the lipid composition of
      the membrane are the central effect of HPV16-E5 on the cell. The multiple and
      apparently disconnected effects of HPV16-E5 on tyrosine-kinase receptors,
      induction of the apoptosis and impairment of MHC trafficking could follow the
      initial alteration on the membrane composition.

PMID- 15503217
TI  - The resurgence of Shamonda virus, an African Simbu group virus of the genus
      Orthobunyavirus, in Japan.
AB  - Six virus isolations were made from Culicoides biting midges and blood samples of
      sentinel cattle in Kagoshima and Miyazaki Prefectures, the southern part of
      Japan, in 2002. Serological and genetical tests identified these viruses as
      isolates of Shamonda virus (SHAV), which belongs to the Simbu group of the genus
      Orthobunyavirus of the family Bunyaviridae. Initially, SHAV was isolated from
      cattle and Culicoides biting midges in Nigeria in the 1960s, and its presence has
      not been reported until this study. The present results indicate a wider
      distribution of SHAV than previously assumed.

PMID- 15503218
TI  - Site directed mutagenesis of the carboxyl terminus of human cytomegalovirus
      glycoprotein B leads to attenuation of viral growth in cell culture.
AB  - A viable human cytomegalovirus (HCMV) mutant was generated harbouring a
      glycoprotein B (gB) in which the carboxyl-terminal amino acids DRLRHR (aa 885
      900) were changed to AALREE. Characterization of the phenotype of the recombinant
      virus revealed significant reduction of infectious progeny release and only
      moderate reduction of viral DNA replication indicating its diminished specific
      infectivity. This observation was in line with immunogold labeling of
      extracellular virions demonstrating that the amount of gB protein was markedly
      reduced in the envelope of the mutant virus. Our results suggest that the
      conserved carboxyl-terminus of the gB molecule is critical for HCMV maturation.

PMID- 15503219
TI  - L protein, the RNA-dependent RNA polymerase of hantaviruses.
AB  - L protein of hantaviruses is the RNA transcriptase and replicase that transcribes
      mRNAs and replicates the genomic RNA using antigenomic RNA as an intermediate. It
      also appears to have endonuclease activity. In this review, the current knowledge
      on the hantavirus L protein is presented including sequence motifs conserved in
      RNA polymerases, mechanisms of RNA synthesis and also the most recent findings on
      homologous RNA recombination and membrane association.

PMID- 15503220
TI  - Characterization of a distinct Johnsongrass mosaic virus strain isolated from
      sorghum in Nigeria.
AB  - A virus isolated from sorghum in Nigeria has been partially characterized. It was
      tested by enzyme-linked immunosorbent assay (ELISA) using antisera to Maize dwarf
      mosaic virus, Johnsongrass mosaic virus (JGMV), Sugarcane mosaic virus strain
      MDB, Sorghum mosaic virus, and Zea mosaic virus. A partial host range, symptom
      phenotypes for selected sorghum lines, and the mass of the coat protein (CP)
      subunit was analyzed by sodium-dodecyl sulfate polyacrylamide gel electrophoresis
      (SDS-PAGE), and its amino acid (aa) sequence determined by time-of-flight mass
      spectrometry (TOFMS). The Nigerian isolate was positive in ELISA to only JGMV
      antiserum. It infected sorghum and smooth brome but not oat or johnsongrass. It
      caused necrosis in 12 of 13 tested sorghum lines, while the USA JGMV isolate
      caused necrosis in only one sorghum line. In SDS-PAGE, the mass of the Nigerian
      virus CP was 3,000 Da smaller than that of JGMV-MDO. Moreover, TOFMS analyses
      showed that, while residues 1-7 of the CP aa sequence were identical to those of
      JGMV (GenBank #A27631), and residues 57-293 were almost identical to residues 67
      303 of JGMV, the intermediate region exhibited significant differences, including
      a 10 aa deletion. These data indicate that the virus should be considered a
      distinct isolate of JGMV (JGMV-N) and expands the known range of JGMV to Africa.

PMID- 15503221
TI  - Nucleotide sequence, genome organization and phylogenetic analysis of Strawberry
      pallidosis associated virus, a new member of the genus Crinivirus.
AB  - The complete nucleotide sequence of Strawberry pallidosis associated virus
      (SPaV), a newly identified member of the genus Crinivirus, family Closteroviridae
      has been determined. RNA 1 is 8067 nucleotides long and encodes at least three
      open reading frames (ORFs). The first ORF (ORF 1a) specifies a multifunctional
      protein that has papain-like proteinase, methyltransferase and RNA helicase
      domains. The RNA-dependent-RNA polymerase is encoded in ORF 1b and is probably
      expressed by a +1 ribosomal frameshift. The 3' ORF of RNA 1 encodes a small
      protein with two potential transmembrane helices. RNA 2 is 7979 nucleotides long
      and encodes 8 ORFs, similar in amino acid sequence and arrangement with those of
      other criniviruses. SPaV encodes the largest structural protein of
      closteroviruses sequenced to date as the minor coat protein of the virus has
      molecular mass of approximately 80 kDa. The 3' non-translated regions share
      nucleotide sequence identities of about 56% and the predicted folding of the non
      translated regions is similar. Phylogenetic analyses reveal that SPaV is related
      most closely to Abutilon yellows virus and Beet pseudo-yellows virus, another
      virus that has been identified recently to cause identical symptoms on strawberry
      indicator plants as SPaV.

PMID- 15503222
TI  - Significance of the genetic relationships deduced from partial nucleotide
      sequencing of infectious bursal disease virus genome segments A or B.
AB  - The rapid genomic characterization of infectious bursal disease virus (IBDV)
      requires determining which partial nucleotide (nt) sequences derived from IBDV
      segments A or B would produce phylogenetic information as significant as
      sequencing the whole corresponding segments. Long nt coding sequences of 27 IBDV
      segments A (aa 20-991) and 21 segments B (aa 7-stop codon) were retrieved from
      databanks and used to compute reference phylogenetic trees using Neighbor Joining
      (NJ) and Parsimony (P): clusters appearing in the NJ and P reference trees with a
      bootstrap value greater than 80% were considered as significant (Whole Segment
      Clusters, WSC). The sequences were then cut into overlapping regions. These were
      used to compute phylogenetic trees which were compared with reference ones. Of
      the partial sequences, the VP2 gene best represented IBDV segment A (10 out of 13
      WSC were conserved), and the 5' two thirds of segment B best represented segment
      B (5 to 6 conserved WSC out of 6). Implementation of the Plato programme finally
      demonstrated that the region encoding VP2 variable domain (vVP2, segment A) is
      the only region of IBDV genome with a significantly different evolution rate,
      which result is consistent with vVP2 being subjected to a high selection
      pressure.

PMID- 15503223
TI  - Aphid transmission of a potyvirus depends on suitability of the helper component
      and the N terminus of the coat protein.
AB  - The present study investigates the specificity of potyviruses for aphid species.
      Two potyviruses differing in their host range were used: Zucchini yellow mosaic
      virus (ZYMV) mainly infecting cucurbits and Turnip mosaic virus (TuMV) mainly
      infecting crucifers. Two sets of aphids species were used as vectors, one
      polyphagous (Myzus persicae and Aphis gossypii) and the other from crucifers
      (Brevicoryne brassicae and Lipaphis erysimi). Evidence is provided that the
      specificity between a vector and a potyvirus depends either on the affinity
      between the aphid species and the helper component (HC) protein used or on the
      affinity between the HC and the virions. The difference between the two
      potyviruses cannot be attributed to the DAG domain which is unaltered in both N
      termini of the CP. Therefore, a ZYMV full length clone served to exchange a
      fragment encoding for the N terminus of the ZYMV CP by that of TuMV. This partial
      exchange in the ZYMV CP, allowed the TuMV HC to transmit the chimeric virus but
      not the wild type ZYMV. The significance of the N terminus context of the CP in
      the specificity for the HC is discussed.

PMID- 15503224
TI  - Expression of multiple foreign epitopes presented as synthetic antigens on the
      surface of Potato virus X particles.
AB  - We describe the construction of recombinant Potato virus X (PVX) vectors
      expressing two different epitopes, ep4 and ep6, from Beet necrotic yellow vein
      virus (BNYVV). The seven-amino-acid epitopes were expressed as N-terminal coat
      protein fusions and were displayed on the surface of PVX particles. Particle
      assembly into full virions was successful even though no wild type coat protein
      subunits were present, and the epitopes could be detected in crude extracts and
      purified virus preparations with appropriate antibodies. A construct containing
      both epitope sequences in tandem was also prepared. The resulting PVX particles
      could be detected by antibodies against ep4 and ep6, either individually or
      simultaneously, showing that both epitopes were accessible. In addition mixed
      infections with PVX vectors containing the individual ep4 and ep6 sequences were
      carried out. This resulted in the formation of PVX particles displaying ep4
      alone, ep6 alone, or both epitopes. These experiments demonstrate for the first
      time that PVX can be utilized to present multiple epitopes, either tandemly on
      every coat protein subunit or as heteromultimeric assemblies, both of which could
      be useful vaccination strategies. The production of epitope-presenting viruses in
      which every coat protein subunit contains a foreign epitope allows the high-level
      expression of defined numbers of foreign antigen sites, making such viruses
      useful standards for immune detection.

PMID- 15503225
TI  - Both Indian cassava mosaic virus and Sri Lankan cassava mosaic virus are found in
      India and exhibit high variability as assessed by PCR-RFLP.
AB  - The biodiversity of geminiviruses associated with the Cassava Mosaic Disease
      (CMD) in India was investigated using PCR to specifically amplify the DNA of
      Indian cassava mosaic virus (ICMV) or Sri Lankan cassava mosaic virus (SLCMV) and
      also by using PCR to amplify specific viral genes, followed by digestion with
      different restriction endonucleases to obtain polymorphic patterns (PCR-RFLP).
      Results showed that both ICMV and SLCMV were present in mosaic-affected cassava;
      ICMV was geographically restricted to certain regions, whereas SLCMV was
      widespread. PCR-RFLP analysis showed that, in addition to ICMV-type and SLCMV
      type patterns, a high proportion (40%) of the samples displayed novel patterns,
      some of which were localized in certain areas, whereas others were widely
      distributed.

PMID- 15503226
TI  - Long-term taurine supplementation reduces mortality rate in streptozotocin
      induced diabetic rats.
AB  - Oxidative stress is implicated in the pathogenesis of diabetes mellitus. Taurine
      and vitamin E+selenium supplementation has some benefits in experimental models
      of diabetes mellitus. This study evaluates whether taurine and vitamin E+selenium
      supplementations reduce a hard end-point such as mortality due to diabetes.
      Streptozotocin-induced diabetic rats were fed with standard diet or taurine (5%,
      w/w) or vitamin E (500 UI/Kg)+selenium (8 mg/Kg) enriched diets. Taurine
      significantly decreased mortality rate (p < 0.04), while vitamin E failed to
      increase survival. In the late phase of the disease, taurine significantly
      decreased glycaemia, being vitamin E ineffective. No correlation between
      glycaemia and survival was found. None of supplementations modified body weight.
      Thus, only taurine decreases the mortality rate and glycaemia. These results
      encourage new research in the field, since classical hypoglycaemic agents are
      unable to decrease mortality in diabetic patients.

PMID- 15503227
TI  - Kinetic study of racemization of aspartyl residues in synthetic elastin peptides.
AB  - We previously reported that biologically uncommon D-aspartyl residues are present
      in sun-damaged skin from elderly people, possibly in elastin. Here, we report the
      kinetics of Asp racemization in model peptides corresponding to elastin sequences
      from exons 6 and 26. We estimated the activation energy (E) of racemization of
      Asp residues, the racemization rates (RR) at 37 degrees C and the time (t)
      required for the D/L ratio of Asp to approximate to 1.0 (D/L ratio of Asp=0.99)
      at 37 degrees C. For an exon 6 peptide, E=29.0 kcal/mol, RR=2.59 x 10(-2)/yr and
      t=101.0 yr. For an exon 26A peptide E=26.2 kcal/mol, RR=4.27 x 10(-2)/yr and
      t=61.3 yr; and for a second exon 26A peptide E=25.7 kcal/mol, RR=5.55 x 10(-2)/yr
      and t=47.0 yr. These results suggest that racemization of Asp residues in elastin
      could occur within a human life span. We propose that D-Asp could be a useful
      molecular indicators of aging.

PMID- 15503228
TI  - Tryptophan administration increase contractility and change the ultrastructure of
      mice duodenum.
AB  - Serotonin (5-HT) is a metabolite of tryptophan (TRP). 5-HT has been shown to
      induce contractions in rat duodenum and ileum. We planned to investigate the in
      vivo effects of TRP administration on duodenal contractility and ultrastructure
      together. Two equal groups of adult male Swiss-albino mice were used in the
      experiments. Controls (CONT) and TRP treated (100 mg/kg/24 hr in 0.2 ml. saline
      solution ip, 7 days). Body weights were recorded at the beginning and at the end
      of experiments. Duodenum tissues contractility responses to different
      concentration of KCl and acethycholine (ACh) were recorded on polygraph. The
      ultrastructural changes in duodenum observed by transmission electron microscopic
      (TEM) method and 5-HT levels determined by immunohistochemical method. Body
      weights decreased and duodenal contractile response of ACh increased
      significantly by TRP treatment. The duodenal ultrastructural changes in TRP group
      illustrated partially loss of apical surface and fusion in microvilli.
      Immunohistochemical detection showed that 5-HT increased by TRP treatment. There
      is a relation between duodenal contractility increased by TRP treatment and
      changes in the duodenal tissue 5-HT level and ultrastructure.

PMID- 15503229
TI  - The effect of taurine administration on vitamin C levels of several tissues in
      mice.
AB  - Taurine (2-aminoethane sulphonic acid), a sulphur-containing beta amino acid, is
      the most prevalent free intracellular amino acid in many human and animal
      tissues. Vitamin C metabolism is also fluenced by sulphur-containing amino acids.
      The aim of this study is to investigate the effect of taurine administration on
      the vitamin C levels of plasma and several tissues (brain, liver, kidneys) in
      mice with incisional skin wounds. Animals were divided into two as control and
      taurine groups. Taurine was freshly dissolved in sterile saline and administered
      daily (60 microl, ip) for five days in the taurine group. At the end of the fifth
      day, the animals were killed by decapitation. The brain, liver and kidneys were
      immediately removed. Vitamin C levels were measured in plasma and several
      tissues. The administration of taurine had no effect on the plasma vitamin C
      levels (P>0.05) but significantly increased in liver and kidneys (P<0.001). In
      conclusion, taurine may affect the vitamin C metabolism in tissues by different
      mechanisms.

PMID- 15503230
TI  - Optimal and effective oral dose of taurine to prolong exercise performance in
      rat.
AB  - The aim of this study was to determine the effective and optimum dose of taurine
      for exercise performance and to maintain tissue taurine concentration. Rats
      received a respective daily dose of 0, 20, 100, and 500 mg/kg body weight of
      taurine (EC and ET-1, -2, -3 groups, respectively) for two weeks, and then, were
      subjected to treadmill until exhaustion. The running time to exhaustion was
      significantly prolonged by 25% and 50% in the ET-2 and -3 groups, respectively,
      compared to that in the EC group accompanied with maintenance of taurine tissue
      concentrations. Furthermore, the oxidative glutathione per total glutathione
      ratio in tissues was inhibited in the ET-2 and -3 groups whereas it was higher in
      the EC group than in both the no exercise and taurine-administered groups.
      Therefore the effective and optimal doses of oral taurine administration for two
      weeks on a transient exercise performance were between 100 and 500 mg/kg/day.

PMID- 15503231
TI  - The enthalpies of interactions of some L-alpha-amino acids with urea molecule in
      aqueous solutions at 298.15 K.
AB  - Dissolution enthalpies of L-alpha-aminobutyric acid, L-alpha-isoleucine, L-alpha
      phenylalanine, L-alpha-methionine, L-alpha-serine, L-alpha-threonine, L-alpha
      cysteine, L-alpha-asparagine and L-alpha-glutamine in aqueous solutions of urea
      have been measured by calorimetry at 298.15 K. The obtained results were used to
      calculate the enthalpic interaction coefficients between the zwitterions of the L
      alpha-amino acids and a molecule of urea in water. These values were interpreted
      in terms of the hydrophobic or hydrophilic effects of the side chains of amino
      acids on their interactions with a polar molecule of urea in water.

PMID- 15503232
TI  - Marfey's reagent for chiral amino acid analysis: a review.
AB  - The present paper describes characteristics and application of Marfey's reagent
      (MR) including general protocols for synthesis of the reagent and diastereomers
      along with advantages, disadvantages and the required precautions. Applications,
      and comparison with other derivatizing agents, for the resolution of complex
      mixtures of DL-amino acids, amines and non-proteinogenic amino acids,
      peptides/amino acids from microorganisms, cysteine residues in peptides, and
      evaluation of racemizing characteristics have been discussed. Separation
      mechanisms of resolution of amino acid diastereomers and replacement of Ala-NH2
      by suitable chiral moieties providing structural analogs and different chiral
      variants and their application as a derivatizing agent to examine the efficiency,
      and reactivity of the reagent have been focussed. Use of MR for preparing CSPs
      for direct enantiomeric resolution has also been included.

PMID- 15503233
TI  - The 40s Omega-loop plays a critical role in the stability and the alkaline
      conformational transition of cytochrome c.
AB  - The structural and redox properties of a non-covalent complex reconstituted upon
      mixing two non-contiguous fragments of horse cytochrome c, the residues 1-38 heme
      containing N-fragment with the residues 57-104 C-fragment, have been
      investigated. With respect to native cyt c, the complex lacks a segment of 18
      residues, corresponding, in the native protein, to an omega (Omega)-loop region.
      The fragment complex shows compact structure, native-like alpha-helix content but
      a less rigid atomic packing and reduced stability with respect to the native
      protein. Structural heterogeneity is observed at pH 7.0, involving formation of
      an axially misligated low-spin species and consequent partial displacement of
      Met80 from the sixth coordination position of the heme-iron. Spectroscopic data
      suggest that a lysine (located in the Met80-containing loop, namely Lys72, Lys73,
      or Lys79) replaces the methionine residue. The residues 1-38/57-104 fragment
      complex shows an unusual biphasic alkaline titration characterized by a low (p
      K(a1)=6.72) and a high p K(a)-associated state transition (p K(a2)=8.56); this
      behavior differs from that of native cyt c, which shows a monophasic alkaline
      transition (p K(a)=8.9). The data indicate that the 40s Omega-loop plays an
      important role in the stability of cyt c and in ensuring a correct alkaline
      conformational transition of the protein.

PMID- 15503234
TI  - Quantification of isomeric equilibria formed by metal ion complexes of 8-[2
      (phosphonomethoxy)ethyl]-8-azaadenine (8,8aPMEA) and 9-[2
      (phosphonomethoxy)ethyl]-8-azaadenine (9,8aPMEA). Derivatives of the antiviral
      nucleotide analogue 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA).
AB  - The acidity constants of the two-fold protonated acyclic 9-[2
      (phosphonomethoxy)ethyl]-8-azaadenine, H2(9,8aPMEA)(+)(-), and its 8-isomer, 8-[2
      (phosphonomethoxy)ethyl]-8-azaadenine, H2(8,8aPMEA)(+)(-), both abbreviated as
      H2(PA)(+)(-), as well as the stability constants of their M(H;PA)+ and M(PA)
      complexes with the metal ions M2+=Mg2+, Ca2+, Sr2+, Ba2+, Mn2+, Co2+, Ni2+, Cu2+,
      Zn2+ or Cd2+, have been determined by potentiometric pH titrations in aqueous
      solution at I=0.1 M (NaNO3) and 25 degrees C. Application of previously
      determined straight-line plots of log K(M)M(R-PO3) versus pK(H)H(R-PO3)for simple
      phosph(on)ate ligands, R-PO3(2-), where R represents a residue without an
      affinity for metal ions, proves that for all M(PA) complexes a larger stability
      is observed than is expected for a sole phosphonate coordination of the metal
      ion. This increased stability is attributed to the formation of five-membered
      chelates involving the ether oxygen present in the aliphatic residue (-CH2-O-CH2
      PO3(2-)) of the ligands. The formation degrees of these chelates were calculated;
      they vary between about 13% for Ca(8,8aPMEA) and 71% for Cu(8,8aPMEA). The
      adenine residue has no influence on complex stability except in the Cu(9,8aPMEA)
      and Zn(9,8aPMEA) systems, where an additional stability increase attributable to
      the adenine residue is observed and equilibria between four different isomers
      exist. This means (1) an open isomer with a sole phosphonate coordination,
      M(PA)op, where PA(2-)=9,8aPMEA2-, (2) an isomer with a five-membered chelate
      involving the ether oxygen, M(PA)cl/O, (3) an isomer which contains five- and
      seven-membered chelates formed by coordination of the phosphonate group, the
      ether oxygen and the N3 site of the adenine residue, M(PA)cl/O/N3, and finally
      (4) a macrochelated isomer involving N7, M(PA)cl/N7. For Cu(9,8aPMEA) the
      formation degrees are 15, 30, 48 and 7% for Cu(PA)op, Cu(PA)cl/O, Cu(PA)cl/O/N3
      and Cu(PA)cl/N7, respectively; this proves that the macrochelate involving N7 is
      a minority species. The situation for the Cu(PMEA) system, where PMEA2-
      represents the parent compound, i.e. the dianion of 9-[2
      (phosphonomethoxy)ethyl]adenine, is quite similar. The relationship between the
      antiviral activity of acyclic nucleoside phosphonates and the structures of the
      various complexes is discussed and an explanation is offered why 9,8aPMEA is
      biologically active but 8,8aPMEA is not.

PMID- 15503239
TI  - [Interobserver variation of the sonographic diagnosis of orbital floor fractures
      and fractures of the infraorbital margin].
AB  - PURPOSE: The aim of the study was to evaluate the interobserver variation of the
      ultrasound diagnosis of orbital floor fractures and fractures of the infraorbital
      rim. MATERIAL AND METHODS: A total of 25 patients with a clinical diagnosis of an
      orbital trauma were investigated prospectively by computed tomography (CT) and
      ultrasonography (US). Inter-observer variation was calculated using the lambda
      coefficient (lambda). The US images were reassessed by two inexperienced
      investigators. RESULTS: The lambda value for the US investigation of the orbital
      floor showed poor reliability comparing the US findings with the results of the
      re-investigators. The comparison between the two re-investigators showed a good
      reliability for the US evaluation of the orbital floor. The lambda for the US
      investigation of the infraorbital margin showed a good reliability comparing the
      US findings with the results of the both re-investigators. The comparison of the
      two re-investigators showed a good reliability as well. CONCLUSION: Ultrasound is
      not yet an alternative method for the evaluation of orbital floor fractures and
      fractures of the infraorbital margin. To replace CT which is accepted as the
      current gold standard, further studies have to be done to reach a better
      diagnostic quality of the method and to achieve a better calibration of the
      investigations.

PMID- 15503240
TI  - A review of incisional hernia repairs: preoperative weight loss and selective use
      of the mesh repair.
AB  - At the Shouldice Clinic pre-operative weight loss is used prior to incisional
      hernia repairs. Mesh repair is selectively used, based on specific hernia
      characteristics. A series of 236 patients were reviewed and followed up for 36
      months. Data were available on 188 patients (80%). There were 15 recurrences
      (8%). The number of obese patients was reduced from 67 (35.6%) to 25 (13.3%)
      through the weight loss program. The hernia diameter, gastrointestinal
      complications, and surgical site infection were significantly related to
      recurrence but not the type of repair, obesity, location, or previous
      recurrences. The risk factors of incisional hernias include size, intestinal
      complications and infections. A selective use has a comparable result to the
      exclusive use of mesh repair. Weight reduction has yet to be shown to affect the
      rate of recurrence, and further prospective studies are required.

PMID- 15503241
TI  - Association analysis of SLC22A4, SLC22A5 and DLG5 in Japanese patients with Crohn
      disease.
AB  - Crohn disease (CD) is an inflammatory bowel disease characterized by chronic
      transmural, segmental, and typically granulomatous inflammation of the gut.
      Recently, two novel candidate gene loci associated with CD, SLC22A4 and SLC22A5
      on chromosome 5 known as IBD5 and DLG5 on chromosome 10, were identified through
      association analysis of Caucasian CD patients. We validated these candidate genes
      in Japanese patients with CD and found a weak but possible association with both
      SLC22A4 (P=0.028) and DLG5 (P=0.023). However, the reported genetic variants that
      were indicated to be causative in the Caucasian population were completely absent
      in or were not associated with Japanese CD patients. These findings imply
      significant differences in genetic background with CD susceptibility among
      different ethnic groups and further indicate some difficulty of population-based
      studies.

PMID- 15503242
TI  - The molecular basis of phenylketonuria in Koreans.
AB  - Phenylketonuria (PKU) is an inborn error of metabolism that results from a
      deficiency of phenylalanine hydroxylase (PAH). We characterized the PAH mutations
      of 79 independent Korean patients with PKU or hyperphenylalaninemia. PAH
      nucleotide sequence analysis revealed 39 different mutations, including ten novel
      mutations. The novel mutations consisted of nine missense mutations (P69S, G103S,
      N207D, T278S, P281A, L293M, G332V, S391I, and A447P) and a novel splice site
      variant (IVS10-3C>G). R243Q, IVS4-1G>A, and E6-96A>G were the most prevalent
      mutations, as they accounted for 32% of the total mutant alleles in this study.
      Although some common characteristics of allele frequency and distribution were
      identified among oriental populations, several distinctive characteristics were
      revealed in Korean patients. Although the R413P allele is the most prevalent form
      (30.5%) in Japanese, we detected it in only five chromosomes from 158 independent
      chromosomes (3.2%). The A259T allele, which has not yet been found in oriental
      populations, was frequently found in this study. We also observed that
      tetrahydrobiopterin (BH4) responsiveness was associated with specific genotypes
      (R53H, R241C, and R408Q), suggesting there are some correlations between
      phenotype and genotype.

PMID- 15503243
TI  - Mutation in the gene encoding lysosomal acid phosphatase (Acp2) causes cerebellum
      and skin malformation in mouse.
AB  - We report a novel spontaneous mutation named nax in mice, which exhibit delayed
      hair appearance and ataxia in a homozygote state. Histological analyses of nax
      brain revealed an overall impairment of the cerebellar cortex. The classical
      cortical cytoarchitecture was disrupted, the inner granule cell layer was not
      obvious, the Purkinje cells were not aligned as a Purkinje cell layer, and
      Bergmann glias did not span the molecular layer. Furthermore, histological
      analyses of skin showed that the hair follicles were also abnormal. We mapped the
      nax locus between marker D2Mit158 and D2Mit100 within a region of 800 kb in the
      middle of chromosome 2 and identified a missense mutation (Gly244Glu) in Acp2, a
      lysosomal monoesterase. The Glu244 mutation does not affect the stability of the
      Acp2 transcript, however it renders the enzyme inactive. Ultrastructural analysis
      of nax cerebellum showed lysosomal storage bodies in nucleated cells, suggesting
      progressive degeneration as the underlying mechanism. Identification of Acp2 as
      the gene mutated in nax mice provides a valuable model system for studying the
      role of Acp2 in cerebellum and skin homeostasis.

PMID- 15503249
TI  - Influence of shear on polypropylene crystallization kinetics.
AB  - Isothermal crystallization kinetics under shear in the melt of iPP was
      investigated by optical microscopy. It appears that shearing from 200 to the
      crystallization temperatures enhanced the kinetics, but the shear effect was not
      obvious if the melt of iPP was sheared only at 200. The experiment results show
      that relaxation plays an important role during crystallization, and that
      spherulite growth rates increased with shear rates and were governed by
      relaxation. The effect of flow on the crystallization kinetics can be understood
      by considering that the increase of the degree of order due to flow results is an
      effective change of the melt free energy. The Laurizen-Hoffman theory and the DE
      IAA model were used to describe the shear-induced crystallization kinetics of iPP
      excellently.

PMID- 15503248
TI  - Effectiveness of different light sources for 5-aminolevulinic acid photodynamic
      therapy.
AB  - Many medical applications, including photodynamic therapy for cancer (PDT),
      involve the use of lasers. However, the coherence of laser light is not necessary
      for PDT, and attempts have been made to construct non-coherent light sources for
      PDT, which are relatively inexpensive, stable and easy to operate, require simple
      maintenance but differ fundamentally from the lasers in their output
      characteristics. In the present work we compared two clinically used lamps,
      CureLight1, which is a broadband source (560-740 nm) based on a filtered halogen
      lamp, and CureLight2, which is a narrowband source based on light-emitting diodes
      (LEDs), with respect to several parameters of crucial significance for PDT
      efficiency in vivo: (a) depth of action in tissues, (b) heating effects, (c) pain
      generation, (d) photodegradation of PpIX in solution, in cells and in mouse skin
      and (e) photo-inactivation of cells in vitro. We conclude that CureLight2 (LED),
      relative to CureLight1 (halogen) has deeper PDT action in tissue, similar
      efficiency for bleaching PpIX in mouse skin, better efficiency for bleaching PpIX
      in cells and solutions and good efficiency for inactivating cells in vitro.
      CureLight2 gives less heating of the tissue and less pain in unsensitised human
      skin. All these differences are related to difference in the spectra of the
      lamps. Thus, PDT light sources with emissions that are visually similar have
      significantly different photobiological properties.

PMID- 15503250
TI  - Wrinkle formations in axi-symmetrically stretched membranes.
AB  - We study experimentally the main features of wrinkles that form in an initially
      stretched and flat elastic membrane when subjected to an axi-symmetric traction
      force at the center. The wavelength and amplitude of the wrinkle pattern are
      accurately characterized as the membrane tension and the traction forced are
      varied. We show that wrinkles are the result of a supercritical instability and
      appear for a well-defined critical traction force that is a function of the
      membrane tension. Wrinkle length and amplitude increase as the traction force is
      increased further. By contrast, both quantities decrease as the membrane tension
      is increased. Calculations based on symmetry arguments and elastic-energy
      minimization are in good agreement with experiments and provide a simple way to
      investigate configurations that are difficult to access experimentally. Such
      problems include wrinkles in elastic nano-films on finite-thickness viscous
      substrates used in semiconductor technology or in cellular forces detection.

PMID- 15503253
TI  - Incisor-molar relationships in chimpanzees and other hominoids: implications for
      diet and phylogeny.
AB  - In chimpanzees, the cutting edge of the incisor battery is longer in relation to
      the length of the molar row than in any other hominoid, extant or fossil, the
      only other lineage approaching it being the orangutan. Apart from their increased
      mesio-distal dimensions, the upper and lower incisors of chimpanzees differ in
      additional ways from those of almost all other hominoids. The I2/ is enlarged, so
      that the difference in size between it and the central upper incisor is less than
      it is in the heteromorphic upper incisors of other hominoids. The lower incisors
      are expanded mesio-distally, so much so that isolated I/2 crowns can resemble
      upper central incisors. In chimpanzees the lingual surface of the lower incisors
      is generally more procumbent than it is in other hominoids, which have more
      vertically oriented incisor crowns and there is a greater difference in enamel
      thickness between labial and lingual sides. The re-orientation of the lower
      incisor crown is reflected in the root, which in lateral view is anteriorly
      concave in chimpanzees whereas it is more orthogonal or convex in other
      hominoids. The molars of chimpanzees, especially the lowers, have extensive and
      relatively deep occlusal basins, and the main cusps are peripheralised and labio
      lingually compressed, making them more trenchant than those of other hominoids.
      This paper examines the incisor-lower molar proportions in extinct and living
      hominoids and develops a new hypothesis about the evolution of the dentition of
      chimpanzees and links it to their diet. It also examines the incisor-molar
      proportions of hominids and African apes in order to throw light on the
      phylogenetic relationships between them. It is shown that chimpanzees are highly
      derived in this respect and that several recent ideas concerning the chimp-like
      appearance of the last common ancestor of hominids and African apes are likely to
      be incorrect.

PMID- 15503255
TI  - [Pathology and histology of soft tissue sarcomas in the upper extremity: adults].
AB  - PURPOSE/BACKGROUND: Clinicopathologic characterization and demonstration of
      histologic findings in six common soft tissue sarcomas of the upper extremity in
      adult patients. RESULTS/CONCLUSION: Clinicopathologic findings and histologic
      features of the following malignant soft tissue tumours are compiled: epithelioid
      sarcoma, synovial sarcoma, clear cell sarcoma, liposarcoma, fibrosarcoma, and
      malignant fibrous histiocytoma (MFH). All these tumours show typical clinical
      presentations and characteristic histological findings.

PMID- 15503254
TI  - Characterization and detection of experimental rat gliomas using magnetic
      resonance imaging.
AB  - Two different experimental rat brain tumours (F98 glioma and 9L glioma) were
      characterized using T1 and T2, apparent diffusion coefficient (ADC) and
      magnetization transfer ratio (MTR). Even though both tumours appeared homogenous
      at the early stage of growth, significant differences were measured for all
      parametric images between tumours and normal brain tissue. Irrespective of the
      sequence used, tumour lesion/normal parenchyma contrast for the non-infiltrative
      9L was twice that of the infiltrative F98 glioma. The use of spin preparation via
      an inversion pulse in a fast spin echo sequence increases contrast by a factor of
      20-30.

PMID- 15503256
TI  - [Soft tissue malignancies in childhood and adolescence. Pathology and clinical
      relevance based on data from the kiel pediatric tumor registry].
AB  - Soft tissue malignancies in childhood and adolescence encompass a wide variety of
      histologically and genetically different tumor entities. In the files of the Kiel
      Pediatric Tumor Registry, 4,272 soft tissue malignancies were collected since
      1977. Rhabdomyosarcomas are by far the most frequent sarcomas (44.6 % of the
      cases), followed in decreasing order of frequency by the family of Ewing tumors
      (peripheral primitive neuroectodermal tumors and extraosseous Ewing's sarcomas;
      altogether 22.3 %), malignant peripheral nerve sheath tumors (8.1 %), synovial
      sarcomas (5.0 %), leiomyosarcomas (3.2 %), fibrosarcomas (2.4 %), extrarenal
      malignant rhabdoid tumors (2.0 %), and alveolar soft tissue sarcomas (1.1 %). A
      further group (11.3 %) includes rare tumors, intermediate fibrohistiocytic
      tumors, and unclassified sarcomas. Embryonal rhabdomyosarcomas are 2.5 times more
      frequent than the alveolar rhabdomyosarcomas, which are prognostically
      unfavorable and located predominantly in the extremities and the trunk. With
      regard to clinical findings, histology, molecular biology and prognosis,
      embryonal and alveolar rhabdomyosarcomas have to be considered as two different
      tumor types. The family of Ewing tumors includes extraosseous Ewing's sarcoma and
      peripheral primitive neuroectodermal tumors (synonym: malignant peripheral
      neuroectodermal tumors), the former tumors without and the latter with neural
      differentiation. Many cases of infantile malignant peripheral nerve sheath tumors
      and infantile fibrosarcomas are low-grade malignancies and prognostically more
      favorable than their "adult" counterparts.

PMID- 15503257
TI  - [Soft tissue sarcoma in children and adolescents: experiences of the cooperative
      Soft Tissue Sarcoma Group Studies (CWS-81 - 96)].
AB  - The very heterogeneous group of paediatric soft tissue sarcomas account for
      approximately 7 % of all malignant childhood tumours. More than one half of all
      cases are rhabdomyosarcomas, some of the over 20 entities are very rare. The
      prognosis and biology of soft tissue sarcomas in children and adolescents vary
      greatly depending on histological subtype, the age of the patient, the primary
      site, the tumour size, tumour invasiveness and the extent of disease at
      diagnosis. Since 1981, 2918 children and adolescents with soft tissue sarcomas
      were treated prospectively according to the common treatment protocols of the
      Cooperative Soft Tissue Sarcoma Study Group (CWS-81 - 96). The known prognostic
      factors were used to develop a more and more detailed risk stratification. The
      multimodal treatment includes the use of surgery, chemotherapy and radiotherapy
      and should be planned by a multidisciplinary team. That way, an overall survival
      of nearly 70 % over all risk groups could be achieved.

PMID- 15503258
TI  - [Goal and results of the COSS study].
AB  - Osteosarcoma is the most common primary malignant tumor of bone (annual
      incidence: 2 - 3/Mio). Ever since 25 years ago, affected children, adolescents,
      and adults from Germany, Austria, and Switzerland receive their therapy within
      trials of the Cooperative Osteosarcoma Study Group (COSS). Approximately 60 % of
      all patients ever entered into COSS-trials could be cured with an
      interdisciplinary treatment approach consisting of complete surgical removal of
      the primary tumor plus intensive pre- and postoperative chemotherapy. The COSS
      group's database now includes information on more than 3,000 osteosarcoma
      patients treated with such a multimodal approach, the largest series worldwide.
      The present paper is intended to detail the experience gathered from this cohort.

PMID- 15503259
TI  - [Tumors of the hand -- results of a long-term study].
AB  - This is a report of a long-term study at the Friedrich-Alexander University of
      Erlangen-Nurnberg, Germany from 1936 to 1994. We divided tumors into three
      categories, i.e. skin, soft tissue and bone tumors. 4612 tumors were included in
      the study. Over the course of the study, a dramatic change in the occurrence of
      single tumors was noticed. While tumor-like lesions have been on the decline,
      other types of tumors, especially malignant tumors as well as more advanced
      stages of tumors have become a common occurrence. We will show that particularly
      larger institutions experience an ever increasing number of advanced tumors
      requiring individual approaches.

PMID- 15503260
TI  - [Positron emission tomography (PET) in soft-tissue sarcoma].
AB  - Positron emission tomography (PET) uses the significantly increased glucose
      metabolism to differentiate malignancies from healthy tissue. This method is well
      established in the oncologic diagnostics of solid epithelial tumours and also in
      breast cancer. In low-grade soft tissue sarcomas specificity and sensitivity are
      limited, however. Not only conventional systems, but also dual headed coincidence
      cameras requiring considerably less technical and economical expenditure can be
      used to produce PET-scans. We have studied the outcome of this technology in 13
      patients with different types of soft-tissue sarcoma. It is our impression that
      both conventional and gamma camera based PET-systems result in similar results in
      soft-tissue sarcoma. Furthermore, in one of the cases presented, PET was able to
      detect metastases considerably earlier than conventional radiography.

PMID- 15503262
TI  - [Primary multicentric cutaneous epithelioid angiosarcoma of the hand. Case report
      and review of the literature].
AB  - CASE: The case of a primary multicentric cutaneous epithelioid angiosarcoma is
      described. A 39-year-old female patient presented with a tumor on the left distal
      forearm and the fourth finger of the left hand. Partial amputation of the left
      hand and local excision of the tumor on the left forearm were performed. For the
      next three years the patient was free of local or systemic recurrence. After this
      time period, a left shoulder exarticulation had to be performed because of tumor
      recurrence in the left axilla. The patient died 64 months after diagnosis.
      CONCLUSION: Cutaneous epithelioid angiosarcoma is a highly malignant tumor which
      has only been described once on the hand. The treatment primarily is a surgical
      one. If possible, the function of the extremity should be preserved as long as
      possible.

PMID- 15503261
TI  - [Free microvascular fibula graft for skeletal reconstruction after tumor
      resections in the forearm -- experience with five cases].
AB  - Plastic-reconstructive surgery for upper extremity tumors not only follows the
      fundamental principles of oncologic surgery, but also requires attention to
      functional and aesthetic aspects. For soft tissue reconstruction, a variety of
      surgical options are available, whereas for the reconstruction of extensive bony
      defects only the free microvascular fibular transplant appears to be a reasonable
      method. Its advantages are its slim shape and variable length, the possibility of
      achieving a stable osteosynthesis suitable for early physiotherapy, and low donor
      site morbidity, even if the fibula is harvested as an osteoseptocutaneous flap.
      Between 1994 and 2000, five patients underwent a free fibula transplantation for
      radius reconstruction. In all cases, a two-stage reconstructive approach with
      initial tumor biopsy was chosen. The resected tumors were two osteosarcomas, one
      extraosseous Ewing sarcoma, one aneurysmatic bone cyst and one desmoplastic
      fibroma. Surgical and pathohistological tumor-free margins were achieved in all
      cases (R(0)). Two patients received an osteocutaneous graft. All grafts were
      revascularized to the radial artery and subcutaneous veins. The transplanted
      fibula grafts were between 10 cm and 17 cm in length. All proximal osteosyntheses
      were performed fibuloradially, the distal stabilizations were fibulo-scapho
      lunate (2 x) and fibulo-radial (3 x), depending on the extent of resection. All
      microvascular transplants survived completely and showed a stable osseous
      integration, both clinically and radiologically. Depending on the postoperative
      course, an adapted intensive physiotherapy regimen yielded good or satisfactory
      function. In the follow-up of up to seven years in one case a tumor recurrence
      (osteosarcoma, 35 months post-operatively) required forearm amputation. The
      reconstruction of tumor-associated wide bony defects in the upper extremity with
      a free microvascular fibula graft allows for a successful therapy with respect to
      oncologic, functional and aesthetic considerations.

PMID- 15503263
TI  - [Epithelioid sarcoma of the hand, a seldomly recognized tumor].
AB  - BACKGROUND: The epithelioid sarcoma of the hand is often misdiagnosed. This tumor
      occurs most frequently in children and young adults, has an uncharacteristic
      course, and carries a high risk for local recurrence and metastases. The
      characteristic histopathology is helpful in establishing the correct diagnosis.
      Differential diagnosis includes synovialoma, fibromatosis and Dupuytren's
      contracture. Multinodular appearance is not uncommon. PATIENTS AND METHOD: Three
      young patients (one male and two female) were operated on the hand for treatment
      of Dupuytren's contracture, synovialoma and fibromas, respectively. The necessity
      for surgical revision in these patients led to a reevaluation of the primary
      histological data. The original diagnosis having been found to be incorrect, the
      correct diagnosis was established namely, epithelioid sarcoma. RESULTS: Surgical
      revision was performed, which involved partial amputation of the extremity. None
      of the patients underwent adjuvant radio- or chemotherapy. The patients were
      followed-up for ten, four and two and a half years, respectively. They are
      currently free of recurrences. CONCLUSION: Prognosis depends on the size and the
      location of the tumor. Adequate treatment requires early radical excision;
      amputation may be required if the primary tumor is located in the fingers or
      treatment of recurrent growth. The tumor tends to metastasize via the lymphatic
      system. Patients must be monitored with yearly lung X-rays since recurrence or
      metastasis may occur many years after the initial diagnosis and treatment.

PMID- 15503264
TI  - [Merkel cell carcinoma -- a case report with regard to the current treatment
      concepts].
AB  - A 54-year-old female patient was admitted due to a slow growing, painless
      resistance on the dorsum of the left hand. The intraoperative aspect of the tumor
      showed a yellow to white doughy tissue mass infiltrating the metacarpal
      musculature and bone. After immunohistopathological staining, the diagnosis of a
      Merkel cell carcinoma was confirmed. A high frequency of local recurrences (25 to
      77 %) and lymph node metastases (50 %) are characteristic features of Merkel cell
      carcinoma. In 30 % of the cases, the disease has a fatal outcome. In primary
      Merkel cell tumors, surgical excision is the basic therapy, although this
      carcinoma is highly radiosensitive. Thus, besides surgical treatment, radiation
      should be included into the treatment concept. In the presented case, after
      radical excision of the tumor and sentinel-lymphnode biopsy, the patient has been
      free of local recurrence and metastases for 13 months.

PMID- 15503265
TI  - [Recurrent chondromatosis of the metacarpophalangeal joint of the thumb --
      differential diagnosis and therapy].
AB  - Primary synovial chondromatosis is a rare and usually monarticular disease. It
      may recur, but the tendency to malignant transformation is very low. The
      differentiation from low-grade chondrosarcoma can be difficult. We present the
      case of a 67-year-old man with synovial chondromatosis in the metacarpophalangeal
      joint of the right thumb which is quite an uncommon localisation.

PMID- 15503266
TI  - [Chondrosarcomas of the hand].
AB  - BACKGROUND: The diagnosis of a chondrosarcoma of the hand can be difficult for
      the surgeon as well as for the pathologist. The histological criteria for
      differentiation between chondrosarcoma and chondroma are not well-defined.
      Nevertheless, distinguishing the two entities is clinically relevant, as
      chondrosarcomas of the hand, despite their low tendency for metastatic spread,
      require a prompt and more radical treatment than chondromas. METHOD AND MATERIAL:
      From 1996 to 2003, we treated four patients with a histologically diagnosed
      chondrosarcoma of the metacarpal bones and phalanges. Two patients were female
      and two male with a mean age of 42 years. The duration between the first clinical
      symptoms and first surgery ranged from two months to 30 years. Three out of four
      patients underwent primary treatment in other institutions, always under the
      histologic diagnosis of a chondroma. The mean follow-up ranged from nine months
      to seven years. RESULTS: The histological diagnosis of chondrosarcoma was
      followed by ray resection in three cases. Two tumors were grade 1 and two tumors
      grade 2. During follow-up, the patients showed no local recurrence and no
      metastatic spread. CONCLUSION: Since the differentiation between chondroma and
      chondrosarcoma is difficult, a good cooperation between surgeon, radiologist and
      pathologist is required. Despite the low metastatic potential of chondrosarcomas
      of the hand in comparison with other sites, ray resection or digital amputation
      is recommended to avoid local recurrence. In cases with only local excision,
      close follow-up is recommended.

PMID- 15503267
TI  - [Recurrent highly-differentiated eccrine carcinoma of the thumb -- a case
      report].
AB  - The eccrine carcinoma is a rare tumour originating from the sweat glands. They
      are mainly located in the palm of the hand and the sole of the foot, the digits,
      the head and the trunk. We report on a now 68-year-old male, who underwent
      partial amputation of the thumb at the level of the proximal phalanx due to an
      eccrine carcinoma in 1990. In the following years, three local recurrences were
      excised. After the exclusion of metastases an amputation at the MP I level was
      performed at our institution. To restore grip function, we performed a
      distraction of the first metacarpal bone followed by deepening of the first web
      space. So far, there are no defined treatment recommendations due to the rarity
      of the tumor. In some cases, metastatic disease has been reported, and in most
      cases, a high rate of local recurrence. After diagnostic biopsy, we recommend
      staging to exclude metastatic spread of the tumor followed by aggressive local
      surgical treatment.

PMID- 15503268
TI  - First-trimester combined ultrasound and biochemical screening for Down syndrome
      in routine clinical practice.
AB  - OBJECTIVES: To assess the effectiveness of combined ultrasound and biochemical
      (CUB) screening for chromosome abnormalities in singleton pregnancies in a
      routine antenatal clinic and laboratory setting. METHODS: Women whose pregnancies
      fell within the gestational age range of 11 to 14 weeks by ultrasound assessment
      were offered CUB screening on the basis of measurement of nuchal translucency
      (NT), maternal serum free beta-human chorionic gonadotrophin (FbetahCG) and
      pregnancy-associated plasma protein A (PAPP-A). NT measurements were obtained
      using a standardised method defined by the Fetal Medicine Foundation and
      FbetahCG, and PAPP-A were measured using the DELFIA immunoassay system. Each
      screening marker measurement was converted to a multiple of the appropriate
      gestational median and a risk was derived using previously published parameters
      for each marker in chromosomally abnormal and unaffected pregnancies. A combined
      risk of Down syndrome and of trisomy 18/13, incorporating the maternal age risk,
      was calculated for all women. Invasive diagnostic testing was offered to women
      whose combined risk exceeded the cut-off risk of 1 in 250 (term). RESULTS: Five
      thousand and eighty-four women accepted a first-trimester screening test for Down
      syndrome, representing 75% of the eligible booking population. Out of the
      population eligible for CUB screening at the time of booking, NT measurements
      were obtained from 93% at the first clinic visit and 7% had to return for a
      second attempt. After excluding women who defaulted on a return visit,
      satisfactory NT measurements were obtained in 99.5% of pregnancies. Fifteen cases
      of Down syndrome and eleven pregnancies with other chromosome abnormalities were
      ascertained. The detection rate for Down syndrome was 93% (14/15) at a false
      positive rate of 5.9% and for all chromosome abnormalities it was 96% (25/26) at
      an overall false-positive rate of 6.3%. CONCLUSIONS: CUB screening offers a
      significant improvement in sensitivity over second-trimester biochemical
      screening and is deliverable within a routine prenatal clinical setting.

PMID- 15503269
TI  - Inbreeding levels and consanguinity structure in the Basque province of Guipuzcoa
      (1862-1980).
AB  - This work analyzes the spatial heterogeneity of consanguinity in the Basque
      province of Guipuzcoa (Spain), using data provided by Catholic dispensations
      (1862-1980). Secular trends in consanguinity rates (%M(C)) and mean inbreeding
      coefficient (F) were similar in the seven Guipuzcoan regions considered, with
      peaks between 1881-1920 and subsequently a gradual decline. Substantial
      differences in consanguinity characteristics emerged when the regions were
      classified according to level of urbanization. Principal component analysis
      (accounting for more than 85% of the total variance in consanguinity variables)
      clearly discriminated between urbanized and less urbanized regions. The latter
      stand out for their high consanguinity rates (3.57-6.73%), mean inbreeding
      coefficient (0.00112-0.00240), and M22/M33 ratio (M22, first cousins; M33, second
      cousins), which ranged between 0.89-1.48. Moreover, in less urbanized regions,
      marital consanguinity was eminently local, and mainly conditioned by regional
      endogamy (71.4-85.0%). By contrast, urban subpopulations showed the lowest
      consanguinity rates (1.60-1.96%) and mean inbreeding coefficient (around 0.0007).
      In these regions, the M22/M33 ratio also exhibited high values (1.07-1.56), but
      this time at the expense of the contribution of the immigrant group. Discussion
      of the factors that could have modeled this spatial variation in consanguinity
      centers on: 1) demographic aspects related to the chronology and intensity of
      industrialization, 2) the geography of the territory and the geography of
      peopling, and 3) linguistic differences, expressed in the uneven distribution of
      Basque-speakers among the different territories considered.

PMID- 15503270
TI  - Clinical, cytogenetic, and molecular analyses of prenatally diagnosed mosaic
      tetrasomy for distal chromosome 15q and review of the literature.
AB  - OBJECTIVES: To present prenatally detected mosaic tetrasomy for distal chromosome
      15q and a review of the literature. CLINICAL SUBJECT AND METHODS: Amniocentesis
      was performed at 17 weeks' gestation because of advanced maternal age.
      Cytogenetic analysis revealed mosaicism for an analphoid supernumerary marker
      chromosome (SMC). The parental karyotypes were normal. Fluorescence in situ
      hybridization (FISH) and polymorphic DNA marker analysis were applied to study
      the origin of the SMC. Level II ultrasound revealed gastric dilation. The
      pregnancy was terminated, and a malformed fetus was delivered with characteristic
      dysmorphism. Multiple samplings of fetal and extraembryonic tissues were
      performed to investigate the mosaicism. RESULTS: Initial amniocentesis revealed
      mos 47,XY,+ mar[20]/46,XY[1], and repeat amniocentesis revealed 47,XY,+
      mar[28]/46,XY[8]. FISH and polymorphic DNA marker analysis determined an origin
      from the distal 15q and an inverted duplication of 15q25.3 --> qter for the SMC.
      Karyotype of the fetus was designated as 47,XY,+ ace i(15) (qter --> q25.3::q25.3
      --> qter)/46,XY de novo. The levels of tetrasomy for distal 15q were 28/40 in
      cord blood, 13/40 in liver, 14/40 in lungs, 27/40 in skin, 0/40 in placenta, and
      40/40 in umbilical cord. The placenta showed an equal biparental inheritance
      (1:1). The umbilical cord inherited one copy of a paternal allele and three
      copies of a maternal allele (1:3) at distal 15q. Diallelic patterns with dosage
      ratios (paternal allele: maternal allele) of 1:2.5 in amniocytes, 1:2.3 in
      amnion, 1:2.2 in cord blood, 1:2.1 in skin, 1:1.4 in liver, and 1:1.4 in lungs. A
      maternal origin of the mosaic SMC(15) was determined. CONCLUSIONS: A diagnosis of
      mosaic analphoid SMCs in amniocytes should alert mosaic mirror-image duplication
      of euchromatin from some distal chromosomal segment such as distal 15q or distal
      13q, and a risk for fetal abnormalities. Fetuses with mosaic tetrasomy for distal
      15q may be associated with fetoplacental chromosomal discrepancy. Postnatal
      samplings of umbilical cord, placenta and amniotic membrane may provide
      additional clues to the cytogenetic discrepancy between fetal and extraembryonic
      tissues in prenatally detected mosaic analphoid SMCs.

PMID- 15503272
TI  - Prenatal diagnosis of spinal muscular atrophy with respiratory distress (SMARD1)
      in a twin pregnancy.

PMID- 15503273
TI  - Prenatal diagnosis of primary anophthalmia with a 3q27 interstitial deletion
      involving SOX2.
AB  - We report an interstitial deletion of chromosome 3q26-q28 in a fetus in which
      anophthalmia had been detected prenatally. FISH analysis, using BAC clones
      encompassing the SOX2 locus, showed that SOX2 gene was involved in the
      chromosomal breakpoint of the deletion. This case confirms that
      haploinsufficiency for SOX2 plays a crucial role in human eye development and
      emphasizes the necessity of careful chromosomal analysis, including FISH analysis
      of the 3q region, in case of prenatal discovery of anophthalmia.

PMID- 15503274
TI  - Which prenatal screening protocol?

PMID- 15503275
TI  - Second-trimester prenatal screening markers for Down syndrome in women with
      insulin-dependent diabetes mellitus.
AB  - Published studies have shown that some serum markers used in screening for Down
      syndrome tend to be lower among women with insulin-dependent diabetes mellitus
      (IDDM). On this basis, many screening programmes adjust the marker levels to take
      account of this difference. Recent studies suggested that the marker levels were
      not different, and so adjustment may no longer be needed, possibly because of
      better diabetic control. Data from a prenatal screening programme for Down
      syndrome were examined to see whether the median values of second-trimester
      screening markers were still reduced in pregnant women with IDDM. A total of 366
      women with IDDM singleton pregnancies without Down syndrome were identified from
      the screening programme at Barts from 1989 to 2002. After allowing for maternal
      weight, the median multiples of the median (MoM) for IDDM-unaffected singleton
      pregnancies were as follows: 0.88 (95% confidence interval 0.84-0.93) for
      alphafetoprotein (AFP), 0.95 (0.91-0.99) for unconjugated oestriol (uE3), 0.90
      (0.80-1.01) for total human chorionic gonadotrophin (total hCG), 0.98 (0.88-1.08)
      for free beta-hCG, and 0.99 (0.89-1.10) for inhibin-A. The median levels for AFP
      and uE3 were statistically significantly lower in pregnant women with IDDM. The
      other markers were not significantly different in women with and without IDDM.
      There remains a case for adjusting AFP and uE3 levels in women with IDDM in
      prenatal screening programmes for Down syndrome.

PMID- 15503276
TI  - A rare case of de novo distal 19q trisomy prenatally diagnosed.
AB  - We present a case of de novo trisomy of distal 19q diagnosed prenatally by
      cytogenetics and FISH analysis. The autopsy performed after termination of the
      pregnancy showed major internal and external malformations that are associated
      with this chromosome abnormality.

PMID- 15503277
TI  - Demonstration of cranial sutures and fontanelles at 15 to 16 weeks of gestation:
      a comparison between two-dimensional and three-dimensional ultrasonography.
AB  - OBJECTIVE: The purpose of this study was to evaluate the feasibility of obtaining
      good quality three-dimensional ultrasound pictures of the cranial sutures and
      fontanelles and to compare between two-dimensional and three-dimensional
      ultrasound in identifying the normal appearance of cranial sutures and
      fontanelles by the transvaginal approach at 15 to 16 weeks of gestation. METHODS:
      Fifty fetuses were prospectively evaluated by two-dimensional and three
      dimensional transvaginal sonography between 15 and 16 weeks of gestation. The
      sagittal, coronal, lambdoidal, and metopic sutures, as well as anterior and
      posterior fontanelles, were inspected. RESULTS: Three-dimensional ultrasound
      enabled visualization of all sutures in 37 (74%) fetuses compared to 28 (56%)
      fetuses examined by two-dimensional ultrasonography (p = NS). The visualization
      of the sagittal suture was significantly superior by three-dimensional
      ultrasonography compared to two-dimensional ultrasonography (50 (100%) vs 35
      (70%), p < 0.001). No significant difference between the two modalities was found
      in visualization of the fontanelles. CONCLUSION: Sutures and fontanelles are
      usually satisfactorily demonstrated by two-dimensional and three-dimensional
      ultrasound at 15 to 16 weeks of gestation. The sagittal suture is difficult to
      visualize using two-dimensional ultrasound, and three-dimensional ultrasound
      appears to be the best method for its demonstration.

PMID- 15503278
TI  - Hemodynamic changes with phenotype reversal during pregnancy in twin-twin
      transfusion syndrome.
AB  - OBJECTIVES: We report an atypical case of twin-twin transfusion syndrome (TTTS)
      in monochorionic-diamniotic twins with arterio-arterial anastomoses in which the
      former donor became the recipient during pregnancy. METHODS: Serial sonographic
      monitoring was performed. RESULTS: There was a phenotype reversal in TTTS
      concerning growth and amniotic fluid ending at 27 weeks, with the dominance of
      the former smaller donor. Doppler sonography changed from absent enddiastolic
      flow of the donor to normal values in both twins. The new recipient showed
      transient ascites, the now smaller actual donor (former recipient) developed
      progressive cardiomegaly, hypertrophy of the myocardium and mitral and tricuspid
      insufficiency at 29 weeks. Doppler sonography in the new donor deteriorated to
      highly pathologic flow in the venous system, leading to cesarean section. The
      donor fetus died 12 h after delivery because of myocardial decompensation. The
      recipient did very well and was discharged 8 weeks later from the neonatology
      unit. CONCLUSION: This atypical course shows the importance of serial sonographic
      monitoring in pregnancies with TTTS.

PMID- 15503279
TI  - Prenatal diagnosis by rapid aneuploidy detection and karyotyping: a prospective
      study of the role of ultrasound in 1589 second-trimester amniocenteses.
AB  - BACKGROUND: Reliable methods are available for rapid aneuploidy detection (RAD)
      for the prenatal diagnosis of trisomies 21, 18 and 13. This study examines the
      potential advantages and limitations of using RAD as a replacement rather than as
      an adjunct to traditional karyotyping. METHODS: One thousand five hundred and
      eighty-nine consecutive pregnancies referred for cytogenetic assessment were
      offered RAD (FISH or QF-PCR) as an adjunct to traditional karyotyping. The
      results of these two processes were compared, and the effects of three policies
      for cytogenetic evaluation were determined: RAD alone, a combination of RAD for
      all and traditional karyotyping for cases with ultrasound anomalies or a policy
      of RAD and traditional karyotyping in all cases. RESULTS: RAD was uninformative
      because of maternal-cell contamination in 37 (2.3%) cases compared to 4 (0.3%)
      cases of culture failure in traditional karyotyping. RAD and traditional
      karyotyping results were concordant in 1526 of 1548 (98.6%) cases. All non-mosaic
      cases of trisomies 21, 18 and 13 and cases of triploidy were correctly identified
      by RAD, and there were no false-positive diagnoses. The gold standard of a
      traditional karyotype in each case would have detected all chromosomal
      abnormalities. A policy of RAD alone would have identified 60 of 73 (82%)
      clinically important chromosomal abnormalities. The addition of a full karyotype
      for cases with evidence of ultrasound abnormalities would have improved detection
      to 95%. CONCLUSION: A policy offering RAD to all patients, but restricting
      traditional karyotyping to cases with ultrasound anomalies, would reduce the
      number of traditional karyotypes requested by 70%, but maintain a 95% detection
      rate for all clinically important chromosomal abnormalities. Further studies are
      required to determine whether similar results could be obtained in district
      general hospital units and to determine whether this approach would be acceptable
      to health professionals and patients.

PMID- 15503280
TI  - Prenatal ultrasound detection of bilateral focal polymicrogyria.
AB  - OBJECTIVES: Prenatal diagnosis by ultrasound of fetal polymicrogyria has been
      reported only once. METHODS: We describe an additional case of polymicrogyria in
      a fetus from a monozygotic twin pair, probably the consequence of twin-to-twin
      transfusion syndrome. RESULTS: On ultrasound, there were bilateral cortical
      hyperechogenic spots, and prenatal magnetic resonance imaging demonstrated the
      typical features of bilateral focal polymicrogyria. CONCLUSION: Polymicrogyria
      can be considered in the differential diagnosis of hyperechogenic brain lesions
      on fetal ultrasound. We also confirm the risk of brain damage in monochorionic
      twins pregnancies and the likely hypoxic-ischemic etiology of polymicrogyria.

PMID- 15503281
TI  - Contingent screening for Down syndrome is an efficient alternative to non
      disclosure sequential screening.
AB  - OBJECTIVE: To present a first and second trimester Down syndrome screening
      strategy, whereby second-trimester marker determination is contingent on the
      first-trimester results. Unlike non-disclosure sequential screening ('the
      Integrated test'), which requires all women to have markers in both trimesters,
      this allows a large proportion of the women to complete screening in the first
      trimester. METHODS: Two first-trimester risk cut-offs defined three types of
      results: positive and referred for early diagnosis; negative with screening
      complete; and intermediate, needing second-trimester markers. Multivariate
      Gaussian modelling with Monte Carlo simulation was used to estimate the false
      positive rate for a fixed 85% detection rate. The false-positive rate was
      evaluated for various early detection rates and early test completion rates.
      Model parameters were taken from the SURUSS trial. RESULTS: Completion of
      screening in the first trimester for 75% of women resulted in a 30% early
      detection rate and a 55% second trimester detected rate (net 85%) with a false
      positive rate only 0.1% above that achievable by the Integrated test. The screen
      positive rate was 0.1% in the first trimester and 4.7% for those continuing to be
      tested in the second trimester. If the early detection rate were to be increased
      to 45% or the early completion rate were to be increased to 80%, there would be a
      further 0.1% increase in the false-positive rate. CONCLUSION: Contingent
      screening can achieve results comparable with the Integrated test but with
      earlier completion of screening for most women. Both strategies need to be
      evaluated in large-scale prospective studies particularly in relation to
      psychological impact and practicability.

PMID- 15503282
TI  - Prenatally diagnosed trisomy 6 mosaicism.

PMID- 15503283
TI  - Third-trimester evaluation of choledochal cyst using magnetic resonance imaging.

PMID- 15503284
TI  - Correlations between nuchal translucency and serum markers in SURUSS.

PMID- 15503285
TI  - Evaluation of fetal cardiac contractility by two-dimensional ultrasonography.
AB  - OBJECTIVE: Evaluation of fetal cardiac contractility by two-dimensional
      ultrasonography and construction of nomograms of area shortening fraction, end
      diastolic area and end-systolic area of fetal cardiac ventricles during
      uncomplicated pregnancy. MATERIALS AND METHODS: Fetal echocardiography was
      performed on 160 pregnant women between 14 and 28 weeks' gestation. Measurements
      were taken on the four-chamber view. The area of each ventricle was measured by
      tracing the endocardium at the end of systole and at the end of diastole. Area
      shortening fraction was calculated by the following formula: SF = (Ad - As)/Ad
      (SF--area shortening fraction, Ad--end-diastolic ventricular area, As--end
      systolic ventricular area). RESULTS: A statistically significant increase in
      normal fetal area shortening fraction, end-diastolic area and end-systolic area
      of both ventricles with advancing gestational age was established. There were no
      significant differences in the area shortening fraction between right and left
      ventricles. CONCLUSIONS: Area shortening fraction shows good correlation with
      gestational age. Nomogram of area shortening fraction, end-diastolic area and end
      systolic area of both ventricles can be used as the reference for evaluation of
      ventricle size and cardiac contractility in normal and pathological cases.

PMID- 15503286
TI  - Nuchal translucency and gestational age.

PMID- 15503287
TI  - First prenatal diagnosis for Wolfram syndrome by molecular analysis of the WFS1
      gene.
AB  - Wolfram syndrome (WS) is an autosomal recessive neurodegenerative disorder
      characterized by early onset diabetes mellitus and progressive optic atrophy in
      the first decade of life. Other clinical features such as diabetes insipidus,
      deafness, renal tract abnormalities or psychiatric illnesses are often present.
      The sequence of the Wolfram syndrome gene (WFS1) was described in 1998, and
      mutations in the gene have been reported in many populations. To date, the
      function of the putative protein remains unknown. Here we report prenatal
      diagnosis by analysing the WFS1 gene, in a foetus belonging to a family with a
      child diagnosed for Wolfram syndrome. The parents are carriers of the c.2206G > C
      (G736R) mutation. To our knowledge this is the first description of prenatal
      diagnosis for Wolfram syndrome, based on the molecular analysis of the WFS1 gene.

PMID- 15503288
TI  - Trisomy 9 screened positive for trisomy 18 by maternal serum screening.

PMID- 15503289
TI  - Prenatal diagnosis of tetrasomy 9p in a 19-week-old fetus with Dandy-Walker
      malformation: a case report.
AB  - OBJECTIVE: The presentation of sonographic and perinatal findings of tetrasomy
      9p. METHODS AND RESULTS: Chorionic villus sampling and amniocentesis were
      performed at 19 weeks of gestation because of the sonographic findings of Dandy
      Walker malformation with bilateral ventriculomegaly. Cytogenetic analysis showed
      47,XX,+i psu dic(9)(pter->q12::q12>-pter). The pregnancy was terminated at 20
      weeks of gestation at the request of the parents. At post-mortem examination, the
      presumed hypoplasia of the vermis could not be confirmed for technical reasons.
      No other pathological findings were seen. CONCLUSION: From our experience and
      from the literature, we conclude that Dandy-Walker malformation is an important
      finding in tetrasomy 9p. Chromosomal studies should be carried out in fetuses
      with sonographically detected Dandy-Walker malformation, even in the absence of
      other abnormalities.

PMID- 15503290
TI  - Changing indications for fetal echocardiography in a University Center
      population.
AB  - OBJECTIVES: We hypothesized that increased facility with fetal echocardiographic
      diagnosis by obstetricians is associated with changes in its indications and
      yields. METHODS: We reviewed 300 fetal echocardiograms (December 2002-August
      2003) and compared our findings with previous studies. RESULTS: Mean maternal age
      was 31 +/- 6 (range 16-44) years. Gestational age was 24 +/- 5 weeks (mean +/-
      SD; median 22, range 15-38). Indications for fetal echocardiography included
      family history of congenital heart disease (CHD) (23%), maternal diabetes (18%),
      obstetrical scan suspicious for CHD (13%), arrhythmia (12%) maternal
      rheumatologic disease (7%), extracardiac congenital anomalies (6%), chromosomal
      anomaly (6%) and exposure to a potential fetal teratogen (5%). High yield
      indications included chromosomal anomaly (47%) and a suspicious obstetrical scan
      (42%). Low yield indications included family history of CHD (4%) and teratogen
      exposure (0%). 1/7 of the patients with increased nuchal translucency had
      pulmonary atresia/intact ventricular septum. No anomalies were associated with
      the single umbilical artery. CONCLUSION: Indications and yields of fetal
      echocardiography have changed over the last decade. The frequency of an
      obstetrical scan suspicious for CHD has increased 2.5 to 3 times over a decade
      and continues to have high yield. Thus, increasing prenatal detection of CHD
      depends, to a large extent, on increasing the skills of obstetricians.

PMID- 15503291
TI  - Imatinib mesylate: an attractive alternative in young children with large,
      surgically challenging dermatofibrosarcoma protuberans.
AB  - To document the clinical activity of imatinib mesyalte in a child with a
      dermatofibrosarcoma protuberans (DFSP). An 18-month-old girl presented with a
      large extremity DFSP. As surgical resection would have caused unacceptable
      functional defects, imatinib mesylate was administered to induce tumor reduction
      and or stabilization. After 23 weeks of therapy, magnetic resonance imaging (MRI)
      of the tumor showed a reduction in the subcutaneous thickness in the transverse
      plane. The drug was tolerated well without any adverse reactions. Imatinib
      mesylate offers a non-surgical alternative for the treatment of large DFSP in
      children.

PMID- 15503292
TI  - Bilateral adrenal cystic neuroblastoma with massive hepatomegaly and intracystic
      hemorrhage.

PMID- 15503293
TI  - Portal hypertension develops in a subset of children with standard risk acute
      lymphoblastic leukemia treated with oral 6-thioguanine during maintenance
      therapy.
AB  - BACKGROUND: 6-Thioguanine (TG) was recently studied to determine whether TG in
      maintenance therapy achieves better event free survival than 6-mercaptopurine
      (MP) for standard risk acute lymphoblastic leukemia (ALL) on the clinical trial,
      CCG-1952 (5/1996-1/2000). Veno-occlusive disease was previously recognized as a
      complication of TG on CCG-1952. We report a newly recognized pediatric
      complication of TG: splenomegaly and portal hypertension (PH) developing during
      maintenance or after completion of therapy. PROCEDURE: Twelve patients (3-10
      years) had been randomized to receive a targeted dose of 50 mg/m(2)/day of TG
      during maintenance phases. Actual TG dose ranged from 25 to 77 mg/m(2)/day
      (median 34 mg/m(2)/day). RESULTS: The initial patient, a boy who had marked
      thrombocytopenia and intermittent splenomegaly during maintenance therapy, was
      evaluated for persistent pancytopenia and progressive splenomegaly 3 months after
      completion of therapy. Dilated splenic vein and collaterals consistent with PH
      were documented by MRI/MRA. Esophagogastroduodenoscopy found esophageal varices.
      Liver biopsy showed periportal fibrosis and marked dilatation of veins and
      venules. Of the other 12 patients, 9 patients studied had abnormal MRI/MRAs with
      evidence of varices in 4. Eight patients had splenomegaly on physical
      examination. Liver biopsies in a girl after 3.3 courses of TG and a boy after 4.6
      courses of TG showed periportal fibrosis and dilatation of venules and sinusoids
      and minimal focal fatty changes. Subsequent MRI/MRAs have been stable or
      improved. CONCLUSIONS: The evaluations of these 12 patients suggest that
      treatment with TG causes injury to the liver leading to PH and that
      thrombocytopenia and splenomegaly are clinical hallmarks of this toxicity.

PMID- 15503294
TI  - High-dose ifosfamide in relapsed pediatric osteosarcoma: therapeutic effects and
      renal toxicity.
AB  - BACKGROUND: Sixteen pediatric osteosarcoma patients, previously treated with
      conventional chemotherapy (including ifosfamide (IFX), 9 g/m(2)) were retreated
      with high-dose ifosfamide (HD-IFX, 14 g/m(2) per course), following relapse or
      development of a new bone tumor. The objective was to obtain responses and an
      improved event-free survival (EFS). PROCEDURE: HD-IFX was administered as
      described by Patel SR: J Clin Oncol 1997;15:2378. Efficacy of treatment was
      assessed initially after two to four courses. The interval between the courses
      was 3 to 4 weeks. Provided a response was obtained after two to four courses,
      treatment was continued for an additional eight courses unless progressive
      disease or an untoward event, for example, renal failure occurred. Tumor sites
      were: lung, (10) bone (9), and bone and soft-tissue (1). RESULTS: Response after
      two to four courses was 62.5%: CR 6 and PR 4. A total of 84 courses were
      administered to the 16 patients: (range 2-10, median 5.5 per patient). Median
      interval between courses was 28.5 days (range 15-90). Five patients were disease
      free at 15+ to 63+ months after induction and maintenance therapy. Fever and
      neutropenia occurred in 12 courses. Nephrotoxicity was a major toxic event and
      was characterized by creatinine levels at or above three times the upper limit of
      normal. It was unpredictable and occurred in four patients: two were reversible.
      The other two patients developed full-blown renal failure; one was treated with
      renal dialysis, but both eventually succumbed to osteosarcoma. Our past
      experience also indicated that two patients treated with IFX (9 g/m(2)/course)
      developed renal failure: one recovered and the other required a renal transplant.
      CONCLUSIONS: HD-IFX is effective in patients who have failed conventional
      chemotherapy including IFX (9 g/m(2)). Improved disease-free survival was
      achieved in 30% of patients. However, renal failure constitutes an important life
      threatening complication and its development is unpredictable.

PMID- 15503295
TI  - Unusual presentation of infantile hemangioendothelioma.
AB  - Infantile hemangioendothelioma is a rare benign hepatic tumor arising from
      mesenchymal tissue. Most of the cases present with congestive heart failure and
      asymptomatic abdominal mass were before 6 months of age. We described a patient
      with projectile vomiting, which is quite an unusual presentation. Following
      surgical resection, neither recurrence nor symptoms were seen in 2 years of
      follow-up.

PMID- 15503296
TI  - Superior mediastinal syndrome with Rowland-Payne syndrome: an unusual
      presentation of cervico-mediastinal neuroblastoma.
AB  - A 5-month-old boy presented with superior mediastinal syndrome due to a large,
      unresectable cervico-mediastinal neuroblastoma. He had an unusual constellation
      of findings not previously reported in neuroblastoma: Horner syndrome, phrenic
      nerve palsy, and palsy of the ipsilateral recurrent laryngeal nerve. This
      constellation of findings in adult malignancies is termed the Rowland-Payne
      syndrome. The child required prolonged mechanical ventilation but responded to
      chemotherapy and is now free of tumor and completely recovered.

PMID- 15503297
TI  - Ifosfamide, carboplatin, and etoposide (ICE) reinduction chemotherapy in a large
      cohort of children and adolescents with recurrent/refractory sarcoma: the
      Children's Cancer Group (CCG) experience.
AB  - BACKGROUND: The prognosis for children with recurrent/refractory sarcomas is
      poor. We determined the overall response rate (ORR) and overall survival (OS) of
      children with recurrent/refractory sarcomas who were given ifosfamide,
      carboplatin, and etoposide (ICE) in three Children's Cancer Group (CCG) phase
      I/II trials. PROCEDURE: Children with recurrent/refractory sarcoma were treated
      with ifosfamide (1,800 mg/m2/day on day 0-4), carboplatin (400 mg/m2/day on day 0
      1), etoposide (100 mg/m2/day on day 0-4) and either rhG-CSF (10 microg/kg/day vs.
      5 microg/kg/day, CCG-0894, 71 patients), PIXY321 (500-1,000 microg/m2/day, CCG
      0924, 14 patients), or rhG-CSF (5 microg/kg/day) and IL-6 (2.5-5 microg/kg/day,
      CCG-0931, 12 patients). RESULTS: Ninety-seven patients were evaluable for tumor
      response, 56 male and 41 female, median age 14.1 years (range 2.8-22.5 years).
      Tumor types were osteosarcoma (OTS) (n = 34), rhabdomyosarcoma (n = 27), Ewing
      sarcoma (EWS) (n = 21), soft tissue sarcoma-not otherwise specified (n = 5),
      undifferentiated sarcoma (n = 6), fibrosarcoma (n = 2), peripheral primitive
      neuroectodermal tumor (n = 1), and extraosseous Ewing (n = 1). The ORR was 51%
      (27% complete response [CR]). OS at 1 and 2 years was 49% and 28%, respectively.
      Patients with CR or partial response (PR) had significantly increased 1- and 2
      year OS, 71% and 41%, respectively, (P < 0.001). Rhabdomyosarcoma patients with
      embryonal histology had significant improvement in 1- and 2-year OS: 82% and 46%,
      respectively, compared with other histologies, (P < 0.005). CONCLUSIONS: The ORR
      to ICE reinduction chemotherapy in children with recurrent/refractory sarcoma was
      51%. OS of 1 and 2 years appeared significantly improved in patients who had CR
      or PR following ICE reinduction therapy or who had rhabdomyosarcoma with
      embryonal histology.

PMID- 15503298
TI  - Pain intensity and bioavailability of intramuscular asparaginase and a local
      anesthetic: a double-blinded study.
AB  - BACKGROUND: To evaluate if dissolution of asparaginase in lidocaine can relieve
      pain of an intramuscular injection in children without changes in
      bioavailability. PROCEDURE: The study was designed as a double-blinded study,
      randomizing 12 children with acute lymphoblastic leukemia (ALL) to four different
      combinations of injections, including two injections where asparaginase was
      dissolved in a lidocaine solution and two in sterile water. Seventeen treatment
      courses of asparaginase, each consisting of four injections, were evaluated. Pain
      intensity (Pain Visual Analog Scale, VAS-score) and pharmacokinetics of the drug
      was evaluated. RESULTS: The pain scores showed a significant difference between
      the two solutions of asparaginase (+/-lidocaine) (P value < 0.0001). Lidocaine
      did not influence the pharmacokinetics of the drug. CONCLUSIONS: Asparaginase
      with addition of lidocaine significantly decreases the pain as measured by the
      visual analog scale without changing the bioavailability or the absorption rate
      of the enzyme.

PMID- 15503299
TI  - Acquired severe aplastic anemia in children: is there a standard of care?

PMID- 15503300
TI  - A novel covalently crosslinked gel of alginate and silane with the ability to
      form bone-like apatite.
AB  - Hybrids consisting of bone-like apatite and biodegradable polymers are attractive
      materials for bone repair. We have shown that an alginate gel crosslinked
      covalently with ethylenediamine (EDA) enhances the repair of skin and nerves. In
      this study, we report a novel method for fabrication of an apatite-alginate
      nanohybrid using a simulated body fluid (SBF). Alginate was reacted with 3
      aminopropyltriethoxysilane (APES), which gives silanol groups after hydrolysis,
      and/or EDA, by dehydration condensation using water-soluble carbodiimide to form
      gels. Modification of alginate with APES alone also gave a gel, because the
      alginate could be crosslinked by dehydration of silanol groups derived from APES.
      The gels obtained were soaked in a 1 mol/L CaCl2 solution and subsequently soaked
      in SBF. Apatite was formed on and inside the alginate gels modified with APES,
      whereas it was not formed on the gels without APES. Modification of alginate with
      silanol groups induced not only gel formation but also the apatite-forming
      ability on and inside the alginate gel in SBF. Consequently, a hydroxyapatite
      alginate hybrid can be produced by modification of alginate with silanol groups
      and subsequent soaking in CaCl2 solution and SBF. Such a material is expected to
      be useful in bone repair.

PMID- 15503301
TI  - Genetic testing in Parkinson's disease.
AB  - Parkinson's disease (PD) is a common neurodegenerative disorder of adulthood
      characterized clinically by rigidity, bradykinesia, resting tremor, and postural
      instability. The annual incidence of PD ranges between 16 and 19 individuals per
      100,000 (Twelves et al., Mov Disord 2003;18:19-31). Historically, PD has been
      commonly viewed as an idiopathic or environmentally triggered condition. However,
      as is true with most common conditions, there have been several families reported
      with PD who demonstrate a classic Mendelian pattern of inheritance. To date, nine
      genetic loci have been reported and four pathogenic genes have been identified:
      alpha-synuclein, parkin, DJ1, and PINK1. Families with alterations in these genes
      or linked sites demonstrate either recessive or dominant inheritance patterns and
      may have typical and/or atypical symptoms, with an age of onset extending from
      the second to the sixth decade. Commercial tests for parkin and alpha-synuclein
      mutations are now available. We predict that physicians, particularly
      neurologists, increasingly will be approached for information and referrals
      regarding genetic testing. To assist patients and their families, physicians will
      not only need to know when such testing is likely to yield a meaningful result
      but also be aware of the possible social and emotional consequences of testing.
      The following is a review of what is currently known about the genetics of PD
      within this context. We discuss what is known about genetic testing for
      Huntington's disease, a well-described model for genetic testing in a
      neurodegenerative disorder. We explore the utility, appropriateness, and possible
      implications of genetic testing for diagnostic and presymptomatic purposes.

PMID- 15503303
TI  - Validation of the Positive and Negative Suicide Ideation (PANSI) Inventory in a
      diverse sample of young adults.
AB  - The psychometric properties and factor structure of the Positive and Negative
      Suicide Ideation (PANSI) Inventory are reported. Data from 220 Caucasian, 127
      African American, 42 Latino/Hispanic, and 39 Asian American college students were
      collected and analyzed. Results indicate that the two-factor structure and
      internal consistency of the PANSI were upheld within the minority group sample;
      however, differences in responses to the PANSI subscales across racial/ethnic
      groups were observed. Correlational analyses support the convergent validity of
      the PANSI, although some group differences were noted. The identified group
      differences are discussed in terms of the utility of the PANSI and a potential
      need for separate racial/ethnic norms when assessing suicidal ideation and
      behaviors in diverse individuals.

PMID- 15503302
TI  - c-Myc localization within the nucleus: evidence for association with the PML
      nuclear body.
AB  - Definitive localization of c-Myc within the nucleus is important to fully
      understand the regulation and function of this oncoprotein. Studies of c-Myc
      distribution, however, have produced conflicting results. To overcome technical
      challenges inherent in c-Myc cytology, we use here three methods to visualize c
      Myc and in addition examine the impact of proteasome inhibition. EYFP or HA
      tagged Myc was reintroduced by stable transfection into myc null diploid rat
      fibroblasts, replacing endogenous Myc with tagged Myc expressed at or near normal
      levels. This tagged Myc is shown to functionally replace the endogenous Myc by
      restoration of normal cell morphology and growth rate. We were able to confirm
      key findings using antibodies to the endogenous c-Myc and/or its partner, Max.
      Contrary to some published reports, by all three methods the c-Myc protein in rat
      fibroblasts distributes predominantly throughout the nucleus in a dispersed
      granular pattern, avoiding the nucleolus. Importantly, however, several findings
      provide evidence for an unanticipated relationship between c-Myc and PML nuclear
      bodies, which is enhanced under conditions of proteasome inhibition. Evidence of
      Max concentration within PML bodies is shown both with and without proteasome
      inhibition, strengthening the relationship between PML bodies and Myc/Max. Some
      accumulation of Myc and Max in nucleoli upon proteasome inhibition is also
      observed, although co-localization of ubiquitin was only seen with PML bodies.
      This work provides a comprehensive study of c-Myc distribution and also presents
      the first evidence of a relationship between turnover of this oncoprotein and PML
      nuclear bodies, known to break down in certain cancers.

PMID- 15503304
TI  - The Inventory of Suicide Orientation-30: further validation with adolescent
      psychiatric inpatients.
AB  - The present study examined the construct validity of the Inventory of Suicide
      Orientation-30 (ISO-30; King & Kowalchuk, 1994) with a sample of adolescent
      psychiatric inpatients. The ISO-30 is designed to assess five dimensions of risk
      factors related to suicide: hopelessness, suicide ideation, low self-esteem,
      inability to cope with emotions, and social isolation and withdrawal.
      Participants included 202 psychiatric hospitalized (106 boys, 96 girls)
      adolescents, ages 14 to 17 years. Confirmatory factor analyses provided support
      for the fit of the original five-factor oblique model. Reliability estimates of
      the study measures were adequate. Evidence of discriminant, convergent, and
      incremental validity estimates of the ISO-30 were strong. Contributions and
      limitations of the present findings are discussed.

PMID- 15503305
TI  - Dermatofibrosarcoma protuberans.
AB  - In the current review, the authors set out to discuss the natural history and
      treatment of dermatofibrosarcoma protuberans (DFSP), a rare indolent cutaneous
      tumor. Approximately 10-15% of all DFSPs contain areas of fibrosarcoma (DFSP-FS),
      and such cases tend to exhibit more aggressive behavior. The optimal treatment
      for DFSP is resection with wide margins; the likelihood of local control
      associated with this procedure exceeds 90%. The probability of regional or
      distant metastases is </= 5%. Patients with positive or close surgical margins
      have an elevated risk of local recurrence after resection alone; however,
      postoperative radiotherapy results in local control rates of >/= 85% in such
      patients. Postoperative radiotherapy also is indicated in the rare event that a
      patient has unresectable macroscopic disease. Experience with the use of
      radiotherapy alone to treat macroscopic disease is limited.

PMID- 15503306
TI  - Neovascularization of bone marrow in patients with diffuse multiple myeloma: a
      correlative study of magnetic resonance imaging and histopathologic findings.
AB  - BACKGROUND: The goal of the current study was to assess the correlation between
      bone marrow histology and contrast enhancement in infiltrative diffuse myeloma.
      METHODS: Forty-four patients with homogeneous diffuse infiltration of bone marrow
      by multiple myeloma were examined using magnetic resonance imaging of the spine.
      The sequence protocol included T1-weighted spin-echo (pre- and post-gadolinium
      dimeglumine administration) and short-inversion time inversion recovery
      sequences. The percent increase in signal after intravenous gadolinium
      administration was calculated in bone marrow from patients with myeloma and from
      a control group of 86 patients who did not have bone marrow disease. Grade of
      infiltration with plasma cells, fat cell content, and hematopoietic marrow
      content were evaluated via histologic assessment of bone marrow, and microvessel
      density was evaluated via anti-CD34-positive immunostaining. RESULTS: Increased
      microvessel density was observed in association with increasing plasma cell
      content (Kruskall-Wallis test: P < 0.0001). Contrast enhancement increased in a
      stepwise manner according to grade of microvessel density (Mann-Whitney U test: P
      < 0.05 and P < 0.001 for increases from low to intermediate and intermediate to
      high grade) and was significantly higher in patients with myeloma compared with
      control patients (Mann-Whitney U test: P < 0.001). A significant correlation also
      was found between histologic extent of tumor infiltration and contrast
      enhancement (Mann-Whitney U test: P < 0.0001). The mean level of contrast
      enhancement was 18% in the control group, 26% in patients with low-grade
      infiltration, 49% in patients with intermediate-grade infiltration, and 90% in
      patients with high-grade infiltration. In addition, fat cell content was found to
      be inversely correlated with contrast enhancement (chi-square test: P < 0.01).
      CONCLUSIONS: As a consequence of increased microvessel density, decreased fat
      cell content, and increased cellularity, the presence of diffuse bone marrow
      infiltration in patients with multiple myeloma can be verified using gadolinium
      enhanced magnetic resonance imaging.

PMID- 15503307
TI  - Item difficulty scaling for WAIS-III picture arrangement.
AB  - Only one study regarding the sequencing of items of the WAIS-III Picture
      Arrangement subtest was located in a search of published literature. That study
      of 50 alcohol abusers failed to demonstrate that the items are sequenced in the
      perfect order of difficulty as suggested by the test publisher. The current study
      was accomplished to replicate or refute the prior study and to extend findings
      into related matters. Two laboratories provided four archival samples of 100
      cases. Only five items appear properly placed, with one (OPENS) especially
      misplaced. A new sequence is recommended so that clinicians can administer the
      test more efficiently and examine errors from a process approach to evaluation.
      Difficult items were not passed as often as expected by Hispanic respondents.
      This finding was considered an artifact related to archival convenience sampling
      and may not be representative as a general finding regarding Hispanic performance
      until experimental sampling techniques or proper statistical controls can be
      applied. Statistically controlling for IQ, through analysis of covariance,
      eliminated ethnicity effects on total score for the PA subtest.

PMID- 15503308
TI  - The influence of client characteristics on psychologists' ethical beliefs: an
      empirical investigation.
AB  - Do psychologists' ethical beliefs depend upon client characteristics? In the
      current study, licensed psychologists were surveyed regarding their ethical
      beliefs using an adaptation of a frequently used list of therapist behaviors
      rated for ethicality (Pope, Tabachnick, & Keith-Spiegel, 1987). In the current
      survey, the age, sex, and diagnostic severity of the hypothetical client were
      specified and varied between participants. Results indicated a significant
      interaction between client age and client sex, such that older male clients
      elicited lower overall ethicality ratings than did younger male clients, but
      older female clients elicited higher overall ethicality ratings than did younger
      female clients. This finding was especially robust when a subset of therapist
      behaviors involving assertive or discomforting therapist actions was considered.

PMID- 15503309
TI  - Group supervision in psychotherapy: the relationship between focus, group
      climate, and perceived attained skill.
AB  - This study examined supervisees and supervisors' view on focus and group climate
      in group supervision and their relationship with supervisees' attained skill.
      After supervision, supervisees completed a revised version of Buckley's measure
      of psychotherapeutic skill. Supervisees and supervisors' experience of focus and
      climate in the supervision was measured with a questionnaire, Topics and Climate
      (TAC). The results showed that supervisors' ratings of the extent to which
      different foci were used in the supervision were significantly higher compared to
      supervisees' ratings. Hierarchical regression analysis showed that differences in
      supervisor style were related to supervisees' experience of attained skill.
      Supervisees' experience of the degree to which focus in supervision was on
      psychodynamic processes was positively related to perceived attained skill,
      whereas focus on Theoretical aspects was negatively related. These findings
      underline the importance of research work with topics and group processes in
      group supervision.

PMID- 15503310
TI  - Two schedules of second-line irinotecan for metastatic colon carcinoma.
AB  - BACKGROUND: In a recently reported, randomized trial, it was found that a regimen
      of irinotecan once every 3 weeks for patients with advanced colorectal carcinoma
      was associated with a lower incidence of severe diarrhea compared with weekly
      treatment, and both regimens had similar efficacy. METHODS: Resource utilization
      was captured prospectively for all 291 patients who were included in the trial.
      Utilities were estimated by transformation of the global quality-of-life (QOL)
      item on the Eastern Organization for Research and Treatment of Cancer QLQ-C30
      instrument. RESULTS: Patients in the every-3-week arm incurred an average
      incremental cost of $1362, because they received higher average weekly doses and
      because the every-3-week regimen resulted in less toxicity, allowing delivery of
      97% of the planned doses compared with delivery of only 75% of the planned doses
      in the weekly arm. This lower toxicity also resulted in offsetting savings from
      decreased hospitalization and less requirement for supportive medications. Non
      chemotherapy-related treatment administration costs also were lower, because the
      every-3-week regimen could be delivered with half the number of infusions.
      Utility declined less in the every-3-week arm, resulting in a saving of 6.3
      quality-adjusted days. The base-case cost:utility ratio was $78,627 per quality
      adjusted life year for patients on the every-3-week schedule. However, that ratio
      was very sensitive to the cost of irinotecan. CONCLUSIONS: The schedule of
      irinotecan once every 3 weeks schedule was more costly but achieved lower
      toxicity, resulting in modestly improved utility. The cost-per-utility ratio was
      comparable to other commonly accepted contemporary treatments.

PMID- 15503311
TI  - Therapeutic potential of antisense Bcl-2 as a chemosensitizer for cancer therapy.
AB  - Bcl-2 protein plays a critical role in inhibiting anticancer drug-induced
      apoptosis, which is mediated by a mitochondria-dependent pathway that controls
      the release of cytochrome c from mitochondria through anion channels.
      Constitutive overexpression of Bcl-2 or unchanged expression after treatment with
      anticancer drugs confers drug resistance not only to hematologic malignancies but
      also to solid tumors. The down-regulation of Bcl-2 protein by the antisense (AS)
      Bcl-2 (oblimesen sodium) may be a useful method for targeting the antiapoptotic
      protein and thereby increasing the chemotherapeutic effect of anticancer drugs.
      Several randomized, controlled, Phase III trials have compared standard
      chemotherapy with a combination of AS Bcl-2 and standard chemotherapy for the
      treatment of patients with chronic lymphocytic leukemia, multiple myeloma,
      malignant melanoma, and nonsmall cell lung carcinoma. Nonrandomized clinical
      trials and preclinical evaluations of AS Bcl-2 also are underway for patients
      with other malignancies. Here, the authors review the current clinical and
      preclinical evaluations of AS Bcl-2 and discuss its potential to act as a
      chemosensitizer and to enhance the therapeutic effect of cancer chemotherapy.

PMID- 15503312
TI  - Genetic similarities between Spitz nevus and Spitzoid melanoma in children.
AB  - BACKGROUND: Melanoma in children is rare. Diagnosis of the subtype of melanoma
      known as Spitzoid melanoma can be extremely challenging in this age group.
      Spitzoid melanoma clinically and histopathologically resembles a benign
      melanocytic proliferation referred to as Spitz nevus. In some cases, distinction
      between the two is impossible. Initial misdiagnoses of Spitzoid melanomas as
      Spitz nevi, thus leading to fatal outcomes, have occurred. The genetic basis and
      biologic behavior of Spitzoid melanoma is unknown. Although melanoma specimens
      exhibit high rates of mutation in the B-RAF and N-RAS genes, the Spitzoid
      melanoma subtype has not been evaluated. Spitz nevi have been found to be
      associated with a low percentage of mutations in the H-RAS gene; however, the
      mutational profile of H-RAS in Spitzoid melanoma is unknown. METHODS: The authors
      evaluated a unique series of melanomas occurring in prepubescent children that
      showed Spitz nevus-like histopathology (Spitzoid melanoma). All of the melanomas
      in the current series have metastasized to lymph nodes, confirming the diagnosis
      of melanoma. The authors examined these tumors, as well as age-matched Spitz
      nevi, for mutations in the B-RAF, N-RAS, and H-RAS genes. RESULTS: Activating
      hotspot mutations in the B-RAF, N-RAS, and H-RAS genes were not identified in
      Spitzoid melanoma or Spitz nevus specimens. CONCLUSIONS: There are genetic
      similarities with respect to the B-RAF, N-RAS, and H-RAS genes between Spitzoid
      melanoma and Spitz nevi. Such similarities further differentiate these two tumor
      types from other melanoma subtypes and from melanocytic nevi, respectively.
      However, mutation analysis of B-RAF, N-RAS, and H-RAS was not useful in
      differentiating between Spitzoid melanoma and Spitz nevus in children.

PMID- 15503313
TI  - CD4 lymphopenia as a risk factor for febrile neutropenia and early death after
      cytotoxic chemotherapy in adult patients with cancer.
AB  - BACKGROUND: Lymphopenia is frequently observed in patients with cancer and
      correlates with the risk of febrile neutropenia and early death after
      chemotherapy. The phenotype of the depleted lymphocyte populations was
      investigated in the current study. METHODS: Peripheral blood lymphocyte subsets
      (CD3, CD4, CD8, CD19, CD56) were quantified on Day 1 using fluorescence-activated
      cell sorting in a prospective study of 213 patients with cancer treated with
      chemotherapy in a single oncology ward during 12 months. Correlations between
      lymphocyte phenotype, clinical characteristics, and the risk of febrile
      neutropenia and early death within 31 days after chemotherapy were investigated
      in univariate and multivariate analyses. RESULTS: Total lymphocyte count and CD3,
      CD4, and CD8 lymphocyte subsets were significantly lower in patients who
      experienced febrile neutropenia. Total lymphocyte count and CD3, CD4, CD8, CD19,
      and CD56 lymphocyte subsets were significantly lower in patients who died within
      31 days after chemotherapy. Using logistic regression, CD4 lymphopenia (<
      450/muL; odds ratio [OR] = 2.9, 95% confidence interval [CI] = 1.5-5.9) and the
      dose of chemotherapy (OR = 3,9, 95% CI = 2.0-7.8) were both identified as
      independent risk factors for febrile neutropenia. Fifty-four percent of patients
      with both risk factors experienced febrile neutropenia. CD4 lymphocyte count <
      450/muL was also an independent risk factor for early death (OR = 7.7, 95% CI =
      1.7-35). Thirteen percent of patients with a CD4 lymphocyte count </= 450/muL
      died within 31 days after chemotherapy. Eighty-seven percent (14 of 16) of
      patients who died before Day 31 had a CD4 lymphocyte count < 450/muL.
      CONCLUSIONS: A low CD4 count was an independent risk factor for febrile
      neutropenia and early death in patients receiving cytotoxic chemotherapy.

PMID- 15503314
TI  - Dehydration kinetics of piroxicam monohydrate and relationship to lattice energy
      and structure.
AB  - The dehydration kinetics of piroxicam monohydrate (PM) is analyzed by both model
      free and model-fitting approaches. The conventional model-fitting approach
      assuming a fixed mechanism throughout the reaction is found to be too simplistic.
      The model-free approach allows for a change of mechanism and activation energy,
      Ea, during the course of a reaction and is therefore more realistic. The
      complexity of the dehydration of PM is illustrated by the dependence of Ea on
      both the heating conditions, isothermal or nonisothermal, and on the fraction of
      conversion, alpha (0 < or = alpha < or = 1). Under both isothermal and
      nonisothermal conditions, Ea increases with alpha for 0 < or = alpha < or = 0.25,
      followed by an approximately constant value of Ea during further dehydration. In
      the constant-Ea region, isothermal dehydration follows the two-dimensional phase
      boundary model (R2), whereas nonisothermal dehydration follows a mechanism
      intermediate between two- and three-dimensional diffusion that cannot be
      described by any of the common models. Structural studies suggest that the
      complex hydrogen-bond pattern in PM is responsible for the observed dehydration
      behavior. Ab initio calculations provide an explanation for the changes in the
      molecular and crystal structures accompanying the reversible change in hydration
      state between anhydrous piroxicam Form I and PM. This work also demonstrates the
      utility of model-free analysis in describing complex dehydration kinetics.

PMID- 15503316
TI  - Religious coping and psychological adjustment to stress: a meta-analysis.
AB  - A growing body of literature suggests that people often turn to religion when
      coping with stressful events. However, studies on the efficacy of religious
      coping for people dealing with stressful situations have yielded mixed results.
      No published studies to date have attempted to quantitatively synthesize the
      research on religious coping and psychological adjustment to stress. The purpose
      of the current study was to synthesize the research on situation-specific
      religious coping methods and quantitatively determine their efficacy for people
      dealing with stressful situations. A meta-analysis of 49 relevant studies with a
      total of 105 effect sizes was conducted in order to quantitatively examine the
      relationship between religious coping and psychological adjustment to stress.
      Four types of relationships were investigated: positive religious coping with
      positive psychological adjustment, positive religious coping with negative
      psychological adjustment, negative religious coping with positive psychological
      adjustment, and negative religious coping with negative psychological adjustment.
      The results of the study generally supported the hypotheses that positive and
      negative forms of religious coping are related to positive and negative
      psychological adjustment to stress, respectively. Implications of the findings
      and their limitations are discussed.

PMID- 15503315
TI  - Population pharmacokinetic analysis of pegylated human erythropoietin in rats.
AB  - The purpose of this study was to model the pharmacokinetics of the pegylated
      human erythropoietin (PEG-EPO) after single-dose administration in rats, and to
      evaluate the influence of weight, sex, and pregnancy status on the
      pharmacokinetic parameters. A total of 436 serum concentrations from 193 Sprague
      Dawley rats were obtained from four pharmacokinetic/toxicokinetic studies, in
      which a single dose of PEG-EPO was administered by the intravenous (i.v.; dose
      range: 2.5 to 500 microg/kg) and subcutaneous (s.c.; dose range: 12.5 to 500
      microg/kg) route. Pharmacokinetic analysis was performed using nonlinear mixed
      effect modeling (NONMEM V software) to determine the population mean of
      pharmacokinetic parameters and the variances of the interindividual random
      effects. The effect of weight, sex, and pregnancy status on the pharmacokinetic
      parameters was evaluated by forward inclusion and backward elimination process,
      using the likelihood ratio test. Nonparametric bootstrap analysis was employed as
      an internal model evaluation technique to qualify the model developed. An open
      two-compartment model with linear elimination from the central compartment, a
      first-order absorption with lag time characterized the serum concentration-time
      profiles of PEG-EPO after i.v. and s.c. administration. For a male rat of 0.24
      kg, the average CL, Vc, Q, Vp, Ka, Tlag, and F was estimated to be 0.728 mL/h,
      15.8 mL, 0.373 mL/h, 6.99 mL, 0.0618 h(-1), 3.13 h, and 48.8%, respectively. A
      twofold increase in weight corresponded with a 170 and 238% increase in CL and
      Vc, respectively. In female rats, Vp was reduced by 11%, whereas F was increased
      by 15%. No effect of pregnancy status on any of the parameters could be
      identified. The interindividual variability in CL, Vc, Vp, Ka, and F was
      estimated at 10.7, 14.7, 16.6, 11.0, and 13.6%, respectively. Nonparametric
      bootstrap analysis confirmed the accuracy and the precision of the NONMEM
      parameter estimates. A population pharmacokinetic approach was used to integrate
      the knowledge gathered from several pharmacokinetic/toxicokinetic studies in
      rats. The pharmacokinetics of PEG-EPO in the rat was successfully modeled using a
      two-compartmental model with a linear elimination from the central compartment
      and a first-order absorption process with lag time. Weight and sex, but not
      pregnancy status, were identified as covariates of interest during preclinical
      development. The population pharmacokinetic model developed will be further used
      for the purpose of interspecies scaling and PK/PD modeling.

PMID- 15503317
TI  - The relationship between interpersonal problems and the helping alliance.
AB  - Using data from a large longitudinal naturalistic study on course and outcome of
      psychotherapy, the present paper investigates the amount of interpersonal
      problems in an outpatient sample (N = 714) and the extent to which a patient's
      interpersonal problems determine the quality of the helping alliance. The results
      show that at the beginning of psychotherapy, subjects reported significant
      interpersonal distress on 2.43 of the eight IIP scales. Interpersonal problems
      were most prevalent in the octants "introverted," "submissive," "exploitable,"
      and "overly nurturant." Furthermore, interpersonal problems were related to the
      helping alliance in different ways: "Too hostile" patients reported relatively
      poor initial helping alliance whereas "too friendly" patients rated more
      favorably the relationship to the therapist. However, interpersonal problems at
      intake did not predict the therapeutic alliance one-and-a-half years later. The
      results indicate that a poor initial helping alliance might be reversed during
      the course of treatment. Implications for future research and psychotherapeutic
      practice are discussed.

PMID- 15503318
TI  - A misleading paper on prostate cancer screening.

PMID- 15503319
TI  - In vitro cytocompatibility assessment of beta-tricalcium phosphate/carboxymethyl
      chitin composite.
AB  - A novel bioabsorbable bone substitute composed of a beta-tricalcium phosphate
      (beta-TCP) and a carboxymethyl-chitin (CM-chitin) sodium has been developed.
      Rabbit tibia defects (4 mm in diameter) were repaired after 4 weeks more
      effectively by the composite compared with a sham-operation group. To further
      investigate the biological safety of the components, genotoxicity and
      carcinogenicity of an extract prepared from the composite were determined using
      four different in vitro assays. The main extract component was identified as CM
      chitin sodium [average molecular weight (Mw) approximately 230 kDa] as determined
      by Fourier transform infrared spectroscopy and gel permeation chromatography
      analysis. The concentrations of P and Ca possibly derived from beta-TCP were 17.7
      and 37.1 microg/g, respectively, as determined by inductively coupled plasma mass
      spectroscopy. Both the metabolic activation and nonactivation (-S9) systems of
      the rat microsome S9 fraction were used to perform a genotoxicity evaluation
      using the Ames test and chromosome aberration assay on Chinese hamster lung
      fibroblast cells treated with the extract. In these assays, no genotoxicity was
      detected with doses < or =5 mg/mL (maximum concentration). The cell
      transformation assay using BALB/c 3T3 cells and the metabolic cooperation assay
      with V79 cells both showed negative results for any tumor-promoting activity
      caused by the extract (approximately 5 mg/mL). These results indicate that the
      bioabsorbable beta-TCP/CM-chitin composite is a highly biocompatible bone
      substitute.

PMID- 15503321
TI  - Results of a randomized controlled trail of prostate cancer screening.

PMID- 15503322
TI  - Peak-combination HARP: a method to correct for phase errors in HARP.
AB  - PURPOSE: To introduce a method to correct phase errors (e.g., from B0
      inhomogeneity) in tagging images, which may affect harmonic phase (HARP)
      evaluation. MATERIALS AND METHODS: The phase images corresponding to the negative
      and positive harmonic peaks in k-space are combined before HARP evaluation to
      eliminate any spurious phase. To validate in vivo, two complementary spatial
      modulation of magnetization (CSPAMM) data sets were collected for each volunteer
      and evaluated with conventional HARP, using either the positive or the negative
      harmonic peak, and with peak-combination HARP. RESULTS: Elimination of phase
      distortion by peak combination was observed in vitro and in vivo. Improved
      reproducibility of motion parameters was found with peak-combination HARP.
      CONCLUSION: With peak-combination HARP, reproducibility of contractile parameters
      is improved, and consequently, the number of subjects needed to detect
      statistically significant changes in contractile function can be reduced to one
      third compared to conventional HARP evaluation.

PMID- 15503323
TI  - Magnetic resonance imaging of articular cartilage of the knee: comparison between
      fat-suppressed three-dimensional SPGR imaging, fat-suppressed FSE imaging, and
      fat-suppressed three-dimensional DEFT imaging, and correlation with arthroscopy.
AB  - PURPOSE: To compare signal-to-noise ratios (S/N) and contrast-to-noise ratios
      (C/N) in various MR sequences, including fat-suppressed three-dimensional spoiled
      gradient-echo (SPGR) imaging, fat-suppressed fast spin echo (FSE) imaging, and
      fat-suppressed three-dimensional driven equilibrium Fourier transform (DEFT)
      imaging, and to determine the diagnostic accuracy of these imaging sequences for
      detecting cartilage lesions in osteoarthritic knees, as compared with
      arthroscopy. MATERIALS AND METHODS: Two sagittal fat-suppressed FSE images
      (repetition time [TR] / echo time [TE], 4000/13 [FSE short TE] and 4000/39 [FSE
      long TE]), sagittal fat-suppressed three-dimensional SPGR images (60/5, 40
      degrees flip angle), and sagittal fat-suppressed echo-planar three-dimensional
      DEFT images (400/21.2) were acquired in 35 knees from 28 patients with
      osteoarthritis of the knee. The S/N efficiencies (S/Neffs) of cartilage, synovial
      fluid, muscle, meniscus, bone marrow, and fat tissue, and the C/N efficiencies
      (C/Neffs) of these structures were calculated. Kappa values, exact agreement,
      sensitivity, specificity, positive predictive value, and negative predictive
      value were determined by comparison of MR grading with arthroscopic results.
      RESULTS: The synovial fluid S/Neff on fat-suppressed FSE short TE images, fat
      suppressed FSE long TE images, and fat-suppressed three-dimensional DEFT images
      showed similar values. Fat-suppressed three-dimensional DEFT images showed the
      highest fluid-cartilage C/Neff of all sequences. All images showed fair to good
      agreement with arthroscopy (kappa, 0.615 in FSE short TE, 0.601 in FSE long TE,
      0.583 in three-dimensional SPGR, and 0.561 in three-dimensional DEFT). Although
      the sensitivity of all sequences was high (100% in FSE short TE, FSE long TE, and
      DEFT; 96.7% in SPGR), specificity was relatively low (67.6% in FSE short TE and
      FSE long TE; 85.3% in SPGR; 58.3% in DEFT). The peripheral area of bone marrow
      edema or whole area of bone marrow edema on fat-suppressed FSE images was
      demonstrated as low or iso-signal intensity on fat-suppressed three-dimensional
      DEFT images. CONCLUSION: Fat-suppressed three-dimensional SPGR imaging and fat
      suppressed FSE imaging showed high sensitivity and high negative predictive
      values, but relatively low specificity. The Kappa value and exact agreement was
      the highest on fat-suppressed FSE short TE images. Fat-suppressed three
      dimensional DEFT images showed results similar to the conventional sequences.

PMID- 15503324
TI  - MRI monitoring of Avastin antiangiogenesis therapy using B22956/1, a new blood
      pool contrast agent, in an experimental model of human cancer.
AB  - PURPOSE: To evaluate the diagnostic and prognostic potential of a new protein
      binding contrast medium, B22956/1, for quantitatively characterizing tumor
      microvessels by MRI and monitoring response to antiangiogenic therapy. MATERIALS
      AND METHODS: Dynamic contrast-enhanced MRI (DCE-MRI) was performed in an
      experimental cancer model with the use of the novel protein-binding agent
      B22956/1, a low molecular contrast agent (ProHance), and a macromolecular
      contrast medium, albumin-(Gd-DTPA). MDA-MB-435, a human cancer cell line, was
      implanted in 22 athymic rats. Animals were assigned randomly to a control
      (saline) or drug-treated (Avastin) group. MRI was performed at baseline and after
      nine days of treatment. The transendothelial permeability (KPS) and the
      fractional blood volume (fBV) were estimated from the kinetic analysis of dynamic
      MR data using a two-compartment model. Tumor growth was also measured from
      volumetric MRI. RESULTS: Tumors grew more slowly, although not significantly
      (P=0.07), in the drug-treated group. The KPS determined for B22956/1 decreased
      significantly in the drug-treated group compared to baseline (P <0.05), and
      progressed significantly in the control group. However, no significant changes
      were resolved with the use of ProHance or albumin-(Gd-DTPA). CONCLUSION: With the
      use of appropriate contrast media, the therapeutic effects of an anti-VEGF
      antibody on tumor microvessels can be monitored by dynamic MRI. The dynamic range
      of permeability to B22956/1, and the sensitivity to change of this parameter
      suggest a potential application in the clinical setting.

PMID- 15503325
TI  - Three-dimensional dynamic liver MR imaging using sensitivity encoding for
      detection of hepatocellular carcinomas: comparison with superparamagnetic iron
      oxide-enhanced mr imaging.
AB  - PURPOSE: To assess the diagnostic performance of three-dimensional dynamic liver
      imaging with sensitivity encoding (SENSE), including double arterial phase images
      and increased resolution, by comparing it to superparamagnetic iron oxide (SPIO)
      enhanced magnetic resonance (MR) imaging for the detection of hypervascular
      hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Twenty-seven consecutive
      patients with 50 HCCs underwent Gd-BOPTA-enhanced dynamic imaging using SENSE and
      SPIO-enhanced MR imaging with at least a 24-hour interval between examinations.
      Using a three-dimensional gradient-echo technique applying SENSE, dynamic imaging
      consisting of double arterial phase-, portal phase- and delayed phase-images, was
      obtained. Using T2-weighted turbo spin-echo and T2*-weighted fast imaging with
      steady-state precession sequence, SPIO-enhanced MR imaging was obtained. For
      qualitative analysis, the diagnostic accuracy of both MR examinations for
      detecting the 50 HCCs was evaluated using the alternative free-response receiver
      operating characteristic method. Sensitivity and positive predictive value were
      also evaluated. RESULTS: The mean sensitivity and positive predictive value of
      three-dimensional dynamic imaging with SENSE were 91.3% and 89.2%, respectively,
      and those of SPIO-enhanced imaging were 77.3% and 92.6 %, respectively. There was
      a significant difference in sensitivity between the two images (P <0.05). The
      mean Az value of three-dimensional dynamic imaging with SENSE (0.97 +/- 0.01) was
      significantly higher than that of SPIO-enhanced imaging (0.90 +/- 0.02) (P=0.00).
      CONCLUSION: Three-dimensional dynamic liver MR imaging using SENSE for acquiring
      double arterial phase images is more efficient than SPIO-enhanced MR imaging for
      detecting HCCs.

PMID- 15503326
TI  - Glomerular filtration rate: assessment with dynamic contrast-enhanced MRI and a
      cortical-compartment model in the rabbit kidney.
AB  - PURPOSE: To describe the use of MRI and a cortical-compartment model to measure
      the glomerular filtration rate (GFR), and compare the results with those obtained
      with the Patlak-Rutland model. MATERIALS AND METHODS: Dynamic MRI of rabbit
      kidneys was performed during and after injection of gadoterate dimeglumine. The
      enhancement curves in the aorta and the kidney were analyzed with the cortical
      compartment and Patlak-Rutland models to assess the GFR. RESULTS: A substantial
      correlation was observed between the GFR measured with MRI using the cortical
      compartment model and the plasma clearance of 51Cr-EDTA (r=0.821, P=0.004). No
      significant correlation was observed between the 51Cr-EDTA clearance (r=0.628,
      P=0.052) and the GFR obtained with the Patlak-Rutland model in regions of
      interest (ROIs) encompassing the renal cortex and medulla. A Bland and Altman
      analysis showed that GFR(cortical) (compartment) agreed better with the 51Cr-EDTA
      clearance compared to GFR(Patlak) when ROIs were limited to the cortex. However,
      the GFR values obtained by MRI were lower than the plasma clearance of 51Cr-EDTA.
      CONCLUSION: MRI with a cortical-compartment model provides more accurate
      assessments of glomerular filtration than the Patlak-Rutland model.

PMID- 15503327
TI  - Can the apparent diffusion coefficient be used as a noninvasive parameter to
      distinguish tumor tissue from peritumoral tissue in cerebral gliomas?
AB  - PURPOSE: To determine whether the apparent diffusion coefficient (ADC) can be
      used to distinguish between tumor tissue and peritumoral brain tissue in cerebral
      gliomas. MATERIALS AND METHODS: Twenty-two patients with 44 biopsies were
      enrolled in this study. ADC maps calculated from a diffusion-weighted (DW)
      multislice EPI sequence were coregistered with conventional MR images.
      Neuronavigated biopsies and intraoperative markers were used for correlation with
      the histologic specimens. ADC values and lesion-to-brain ratios of the different
      sequences were calculated and compared for tumor tissue and peritumoral brain
      tissue. A logistic regression analysis was performed to determine the diagnostic
      value of the ADC maps. RESULTS: The ADC values and ratios demonstrated a large
      overlap between tumor tissue and peritumoral tissue. Group comparisons revealed a
      significantly (P=0.03) lower ADC ratio in tumor tissue (mean=1.28 +/- 0.39)
      compared to peritumoral tissue (mean=1.48 +/- 0.30), whereas the absolute ADC
      values did not differ significantly. In the logistic regression analysis, the
      lesion-to-brain ratio of the gadolinium (Gd)-enhanced T1-weighted sequence was
      the most valuable predictor of the presence of tumor tissue. The ADC value and
      ratio were not identified as significant predictors. CONCLUSION: The ADC is not
      helpful for distinguishing tumor tissue from peritumoral brain tissue in gliomas.

PMID- 15503328
TI  - Quantitative proton MR spectroscopic imaging of the mesial temporal lobe.
AB  - PURPOSE: To evaluate variations in regional metabolite concentrations in the
      anterior mesial temporal lobe (ATL), and compare metabolite concentrations
      between the allocortex and neocortex using quantitative proton MR spectroscopic
      imaging (MRSI). MATERIALS AND METHODS: Metabolite concentrations and ratios were
      measured in 20 healthy young subjects with the use of a multislice spin-echo (SE)
      sequence (TR/TE=2300/280 msec). Quantitation of MRSI data was performed by means
      of the phantom replacement methodology. RESULTS: The highest choline (Cho)
      concentration (4.1 +/- 1.1 mM) was found in the ATL (P=0.0015 compared to the
      middle mesial temporal lobe (MTL), and P=0.0008 compared to the posterior mesial
      temporal lobe (PTL)). The ATL also had a higher Cho/creatine (Cr) ratio and a
      lower N-acetyl aspartate (NAA)/Cho ratio compared to other examined regions (P
      <0.0001 and P < or = 0.052, respectively). In the allocortical regions, the
      average Cho concentration (3.5 +/- 0.8 mM) was 68% higher, and the NAA
      concentration (9.5 +/- 1.8 mM) was 13% lower than in the neocortex (P <10(-6) and
      P <0.008, respectively). Cho/Cr was 64% higher, NAA/Cr 14% lower, and NAA/Cho 47%
      lower in the allocortex than in the neocortex (P <10(-6), P=0.013, and P <10(-6),
      respectively). CONCLUSION: The mesial temporal lobe shows high levels of Cho,
      which presumably reflect a difference in cellular composition between the
      allocortex and neocortex. Regional metabolite variations must be considered when
      pathological conditions involving the mesial temporal lobe are evaluated.

PMID- 15503329
TI  - Discovery and disclosure of incidental findings in neuroimaging research.
AB  - PURPOSE: To examine different protocols for handling incidental findings on brain
      research MRIs, and provide a platform for establishing formal discussions of
      related ethical and policy issues. MATERIALS AND METHODS: Corresponding authors
      identified from a database of peer-reviewed publications in 1991-2002 involving
      functional MRI (fMRI), alone or in combination with other imaging modalities,
      were invited to participate in this web-based survey. The survey asked questions
      regarding knowledge and handling of incidental findings, as well as
      characteristics of the scanning environment, training required, IRB protocol
      requirements, and neuroradiologist involvement. RESULTS: Seventy-four
      investigators who conduct MRI studies in the United States and abroad responded.
      Eighty-two percent (54/66) reported discovering incidental findings in their
      studies, such as arteriovenous malformations, brain tumors, and developmental
      abnormalities. Substantial variability was found in the procedures for handling
      and communicating findings to subjects, neuroradiologist involvement, personnel
      permitted to operate equipment, and training. CONCLUSION: Guidelines for minimum
      and optimum standards for detecting and communicating incidental findings on
      brain MRI research are needed.

PMID- 15503330
TI  - Comparative study of methods for determining vascular permeability and blood
      volume in human gliomas.
AB  - PURPOSE: To characterize human gliomas using T1-weighted dynamic contrast
      enhanced MRI (DCE-MRI), and directly compare three pharmacokinetic analysis
      techniques: a conventional established technique and two novel techniques that
      aim to reduce erroneous overestimation of the volume transfer constant between
      plasma and the extravascular extracellular space (EES) (Ktrans) in areas of high
      blood volume. MATERIALS AND METHODS: Eighteen patients with high-grade gliomas
      underwent DCE-MRI. Three kinetic models were applied to estimate Ktrans and
      fractional blood plasma volume (vp). We applied the Tofts and Kermode (TK) model
      without arterial input function (AIF) estimation, the TK model modified to
      include vp and AIF estimation (mTK), and a "first pass" variant of the TK model
      (FP). RESULTS: KTK values were considerably higher than KmTK and KFP values (P
      <0.001). KmTK and KFP were more comparable and closely correlated (rho=0.744),
      with KmTK generally higher than KFP (P <0.001). Estimates of vp(mTK) and vp(FP)
      also showed a significant difference (P <0.001); however, these values were very
      closely correlated (rho=0.901). KTK parameter maps showed "pseudopermeability"
      effects displaying numerous vessels. These were not visualized on KmTK and KFP
      maps but appeared on the corresponding vp maps, indicating a failure of the TK
      model in commonly occurring vascular regions. CONCLUSION: Both of the methods
      that incorporate a measured AIF and an estimate of vp provide similar
      pathophysiological information and avoid erroneous overestimation of Ktrans in
      areas of significant vessel density, and thus allow a more accurate estimation of
      endothelial permeability.

PMID- 15503331
TI  - Reversible heterogeneous arterial phase liver perfusion associated with transient
      acute hepatitis: findings on gadolinium-enhanced MRI.
AB  - PURPOSE: To assess a possible correlation between active acute hepatitis and the
      development of abnormal liver perfusion demonstrated as heterogeneous enhancement
      on arterial phase gadolinium-enhanced MRI. Dynamically-enhanced MRI of the liver
      can detect reversible perfusion abnormalities that correlate with acute
      hepatitis. MATERIALS AND METHODS: Six patients presenting with symptoms and
      clinical findings in keeping with transient acute hepatitis underwent serial MRI
      of the liver throughout the course of the disease. Serial liver enzyme analysis
      was performed for all six patients, and histopathology was assessed for three
      patients. Imaging included gadolinium-enhanced arterial and venous-phase gradient
      echo sequences. RESULTS: Arterial phase gadolinium-enhanced MRI showed abnormal
      irregular liver perfusion in the setting of acute hepatitis, and the degree of
      irregularity, as well as the persistence of irregular enhancement into the venous
      phase, correlated with the clinical severity of the disease. CONCLUSION: Acute
      hepatitis can cause irregular enhancement of the liver on arterial-phase,
      gadolinium-enhanced, gradient-echo MRI, a reversible finding that improves with
      clinical improvement of the disease.

PMID- 15503332
TI  - Contrast-enhanced peripheral magnetic resonance angiography using time-resolved
      vastly undersampled isotropic projection reconstruction.
AB  - PURPOSE: To investigate the application of time-resolved vastly undersampled
      isotropic projection reconstruction (VIPR) in contrast-enhanced magnetic
      resonance angiography of the distal extremity (single station), and peripheral
      run-off vasculature in the abdomen, thigh, and calf (three stations). MATERIALS
      AND METHODS: Time-resolved distal extremity imaging was performed using VIPR
      sequence through the comparison of two acquisition matrix sizes: 256 with
      TR/TE=3.7/1.4 msec and 320 with TR/TE=4.5/1.8 msec under the same scan time of
      two minutes. VIPR acquisition was combined with a bolus-chase technique to image
      the peripheral run-off vasculature. The time-resolved images were reconstructed
      using a revised sliding window reconstruction filter whose temporal aperture
      remained narrow for low spatial frequencies and increased quadratically to
      include all the projection data for high spatial frequencies. RESULTS: The new
      temporal filter significantly suppressed the undersampling streak artifacts and
      venous contamination, while maintaining a high temporal resolution. Both high
      spatial resolution (ranging from 1.56 x 1.56 x 1.56 mm to 1.25 x 1.25 x 1.25 mm)
      and high temporal resolution (three seconds per frame) distal extremity images
      and peripheral run-off images were generated using time-resolved VIPR
      acquisition, which provides isotropic spatial resolution and isotropic coverage.
      CONCLUSION: Time-resolved VIPR acquisition was demonstrated to be well suited for
      distal extremity imaging by providing isotropic spatial resolution, isotropic
      coverage, and high temporal resolution. The combination of time-resolved VIPR and
      bolus chase technique provided a novel approach for peripheral run-off
      examinations.

PMID- 15503334
TI  - MRA is useful as a follow-up technique after endovascular repair of aortic
      aneurysms with nitinol endoprostheses.
AB  - PURPOSE: To evaluate whether MR angiography (MRA) is a useful tool for the follow
      up of aortic aneurysms treated with nitinol endoluminal grafts. MATERIALS AND
      METHODS: We examined 28 patients treated with nitinol endovascular stents to
      repair an aortic aneurysm with CT angiography (CTA) and MRA. Eleven patients
      (group 1) underwent an MRA after a positive CTA for endoleak was observed.
      Afterwards, 17 patients (group 2) were scheduled for both follow-up examinations.
      The kind of endoleak that occurred and the maximum aortic diameter were compared.
      The sensitivity of CTA relative to MRA for detecting endoleaks in group 2 was
      calculated. Signal-to-noise ratios (SNRs) were measured in the aortoiliac lumen
      at the arterial phase in, above, and below the endoprostheses. Student's t-test
      was used to compare aneurysm dimensions and SNR measurements. RESULTS: Three type
      III leaks were correctly assessed at both examinations; however, CTA was less
      sensitive (50%) than MRA in depicting type II or unclassified leaks. No
      differences in aneurismal size were observed between the two examinations or
      between arterial SNRs observed in or out of the devices. CONCLUSION: MRA can
      provide all relevant information necessary for the follow-up of patients treated
      with nitinol endoprostheses, and performs better than CTA in detecting endoleaks.

PMID- 15503333
TI  - Detection of myocardial infarctions by acquisition-weighted 31P-MR spectroscopy
      in humans.
AB  - PURPOSE: To determine whether the recently applied technique of acquisition
      weighted 31P-MR spectroscopy (AW-MRS) allows for the detection of depressed
      energy metabolism in patients with inferior wall myocardial infarctions.
      MATERIALS AND METHODS: Eight patients with subacute myocardial infarction and
      wall motion abnormalities restricted to the inferior wall were examined with a
      1.5-T MR scanner. Global and regional left ventricular (LV) function was assessed
      by cine MRI, and the size and extent of myocardial infarction was assessed by
      late enhancement (LE). MRS was performed with an AW three-dimensional chemical
      shift imaging sequence. Phosphocreatine/ATP ratios were determined with the
      postprocessing model AMARES for four voxels positioned in the anterior, lateral,
      inferior, and septal parts of the LV. RESULTS: The LV ejection fraction (EF) was
      reduced to 37.5%+/-9.0%. Seven of eight patients had transmural LE in the
      inferior wall, and one patient showed subendocardial enhancement in the inferior
      lateral parts. Phosphocreatine/ATP ratios of the inferior wall were significantly
      reduced (P <0.05) compared to all other parts of the LV (1.03 +/- 0.39
      (inferior), 1.67 +/- 0.81 (lateral), 1.73 +/- 0.29 (anterior), and 1.49 +/- 0.31
      (septal)). The ratios in five of seven patients with transmural enhancement were
      <1.00 in the inferior wall. CONCLUSION: Acquisition weighting allows for the
      detection of inferior wall infarctions in patients. Transmural signal enhancement
      is associated with significant depression of phosphocreatine/ATP ratios.

PMID- 15503335
TI  - In vivo structural imaging of the rat brain with a 3-T clinical human scanner.
AB  - PURPOSE: To examine the feasibility of using product acquisition software on a 3
      T human MRI system to acquire high-resolution structural brain images in the rat.
      MATERIALS AND METHODS: Three sets of dual spin-echo, high-resolution (0.234 x
      0.234 mm in-plane, 0.5 mm thick) images covering the entire rat brain were
      collected and averaged in 66 min. The images had sufficient signal-to-noise ratio
      (SNR) and resolution for visual identification and manual outlining of exemplary
      structures, including the lateral ventricles and dorsal and ventral portions of
      the hippocampus. Further, the data were adequate for unsupervised, automated
      segmentation, permitting quantification of the dorsolateral ventricles. The
      images compared favorably with those collected on a 7-T system. RESULTS:
      Interrater reliabilities (intraclass correlations) of manual ventricular scoring
      were greater than 0.97, and manual vs. automated correlations were 0.97. The
      variability of lateral ventricular size across animals was substantially higher
      than that of the hippocampus. CONCLUSION: The large variability of some brain
      structures that can exist across even a highly selected strain of rats can
      readily be detected with the use of human 3-T systems for the study of small
      animals.

PMID- 15503336
TI  - Diffusion-weighted imaging of the parotid gland: Influence of the choice of b
      values on the apparent diffusion coefficient value.
AB  - PURPOSE: To determine how the ADC value of parotid glands is influenced by the
      choice of b-values. MATERIALS AND METHODS: In eight healthy volunteers, diffusion
      weighted echo-planar imaging (DW-EPI) was performed on a 1.5 T system, with b
      values (in seconds/mm2) of 0, 50, 100, 150, 200, 250, 300, 500, 750, and 1000.
      ADC values were calculated by two alternative methods (exponential vs.
      logarithmic fit) from five different sets of b-values: (A) all b-values; (B) b=0,
      50, and 100; (C) b=0 and 750; (D) b=0, 500, and 1000; and (E) b=500, 750, and
      1000. RESULTS: The mean ADC values for the different settings were (in 10(-3)
      mm2/second, exponential fit): (A) 0.732+/-0.019, (B) 2.074+/-0.084, (C) 0.947+/
      0.020, (D) 0.890+/-0.023, and (E) 0.581+/-0.021. ADC values were significantly (P
      <0.001) different for all pairwise comparisons of settings (A-E) of b-values,
      except for A vs. D (P=0.172) and C vs. D (P=0.380). The ADC(B) was significantly
      higher than ADC(C) or ADC(D), which was significantly higher than ADC(E). ADC
      values from exponential vs. logarithmic fit (P=0.542), as well as left vs. right
      parotid gland (P=0.962), were indistinguishable. CONCLUSION: The ADC values
      calculated from low b-value settings were significantly higher than those
      calculated from high b-value settings. These results suggest that not only true
      diffusion but also perfusion and saliva flow may contribute to the ADC.

PMID- 15503337
TI  - Three-dimensional analysis of mandibular morphology in Otolemur.
AB  - Euclidean distance matrix analysis (EDMA) of three-dimensional data is used here
      to examine mandibular morphology between two species of galagos. Otolemur
      crassicaudatus consumes primarily exudates, while O. garnettii is more
      frugivorous. Acquisition of exudates involves either gouging or scraping tree
      bark, and may involve different forces at the mandible than incising fruits.
      Previous studies of mandibular morphology in exudate-feeding primates produced
      mixed results, some suggesting that morphological specializations reflect
      adaptations for greater force at the anterior dentition, while others suggest
      specializations for producing a large gape. This study addresses these
      controversies by testing predictions associated with O. crassicaudatus generating
      greater force at the anterior dentition or producing a larger gape relative to O.
      garnettii. In addition, this study tests predictions associated with
      specializations of the anterior dentition in O. crassicaudatus as related to
      exudate-feeding. Crania and mandibles from 28 O. crassicaudatus and 17 O.
      garnettii were digitized in three dimensions, using 18 landmarks that summarize
      the shape of the jaw. Two-dimensional measurements were taken to assess incisor
      robusticity. All three-dimensional data were analyzed using EDMA, and bootstrap
      tests were executed to identify specific interlandmark differences that were
      driving any significant (P < 0.05) overall shape differences. Two-dimensional
      data were analyzed using Student's t-test for independent measures. Results
      revealed that there was a significant shape difference in mandibles between
      species, and that mandibles of O. crassicaudatus showed higher condyles, longer
      mandibles, decreased incisor procumbency, and greater incisor robusticity
      relative to O. garnettii. It is suggested that the results of the present study
      reflect adaptations for scraping in O. crassicaudatus rather than gouging.

PMID- 15503338
TI  - Voxel-based analysis of MTR images: a method to locate gray matter abnormalities
      in patients at the earliest stage of multiple sclerosis.
AB  - PURPOSE: To determine whether voxel-based analysis of magnetization transfer
      ratio (MTR) maps can provide evidence of a coherent pattern of gray matter (GM)
      macroscopic and microscopic tissue damage in patients at the earliest stage of
      multiple sclerosis (MS). MATERIALS AND METHODS: We acquired GM MTR maps in 18
      patients with clinically isolated syndrome suggestive of MS (CISSMS), and 18 sex-
      and age-matched healthy controls. We evaluated the clinical status of the
      patients using the MS functional composite score and the expanded disability
      status scale. A two-sample t-test (P <0.0001, k=20, uncorrected for height
      threshold) was used to compare GM MTR maps from patients and controls on a voxel
      by-voxel basis. We then extracted data from regions with t-values above the
      statistical threshold to verify the significance of differences using a
      nonparametric Mann-Whitney U-test. RESULTS: A between-groups comparison of GM
      maps revealed large abnormalities in the basal ganglia, including the bilateral
      thalamus, bilateral lenticular nucleus, bilateral head of caudate, and
      protuberance, and smaller abnormalities in the right insula, right BA 4, and left
      BA 40. The MTR measured in the left caudate and right insula was inversely
      correlated with duration following the first clinical event. CONCLUSION: These
      results suggest that although MS is a multifocal demyelinating disease that
      affects white matter (WM), a pattern of tissue damage is present inside the GM
      involving predominantly basal ganglia at the earliest stage of the disease.

PMID- 15503339
TI  - Age-related differences in serum gonadotropin (FSH and LH), salivary
      testosterone, and 17-beta estradiol levels among Ache Amerindian males of
      Paraguay.
AB  - Age-related differences in serum luteinizing hormone (LH), follicle-stimulating
      hormone (FSH), salivary testosterone, and 17-beta estradiol levels are reported
      for Ache Amerindian males (n = 17; mean age, 37.1 +/- 14.2 SD) of Paraguay in
      order to explore population variation in patterns of male reproductive senescence
      in a foraging/agricultural community. Hormone associations were examined to test
      various hypotheses for age-related differences in hypothalamic-pituitary
      function. Significant increases in FSH (r = 0.75, P < 0.0005) and LH (r = 0.65, P
      < 0.01) were noted in association with aging. No significant correlation was
      observed between morning or evening testosterone and age. Morning and evening
      estradiol levels were associated with morning and evening testosterone,
      respectively (morning, r = 0.53, P = 0.05; evening, r = 0.63, P = 0.02). Evening
      estradiol was also positively associated with LH (r = 0.66, P = 0.02), suggesting
      testicular production to be an important source of circulating estradiol. Morning
      estradiol tended to rise with age, but was not significant (r = 0.39, P = 0.15).
      Anthropometric measurements of height, weight, body mass index, and fat percent
      did not change significantly with age. In contrast to testosterone, age-related
      differences in gonadotropin levels may be independent of energetic status, less
      variant, and more universal among male populations. Implications for gonadotropin
      function and aging on human male reproductive senescence and life histories are
      discussed.

PMID- 15503340
TI  - Brief communication: Is variation in the cranial capacity of the Dmanisi sample
      too high to be from a single species?
AB  - This study uses data resampling to test the null hypothesis that the degree of
      variation in the cranial capacity of the Dmanisi hominid sample is within the
      range variation of a single species. The statistical significance of the
      variation in the Dmanisi sample is examined using simulated distributions based
      on comparative samples of modern humans, chimpanzees, and gorillas. Results show
      that it is unlikely to find the maximum difference observed in the Dmanisi sample
      in distributions of female-female pairs from comparative single-species samples.
      Given that two sexes are represented, the difference in the Dmanisi sample is not
      enough to reject the null hypothesis of a single species. Results of this study
      suggest no compelling reason to invoke multiple taxa to explain variation in the
      cranial capacity of the Dmanisi hominids.

PMID- 15503341
TI  - Analysis of quantitative methods for rib seriation using the Spitalfields
      documented skeletal collection.
AB  - Accurate rib seriation is essential in forensic anthropology and bioarchaeology
      for determination of minimum numbers of individuals, sequencing trauma patterns
      to the chest, and identification of central ribs for use in age estimation. We
      investigate quantitative methods for rib seriation based on three metric
      variables: superior (anterior) costo-transverse crest height (SCTCH), articular
      facet of the tubercle-to-angle length (AFTAL), and head-to-articular facet length
      (HAFL). The sample consists of complete but unseriated sets of ribs from 133
      individuals from the documented (known age and sex) and undocumented skeletal
      collections of Christ Church Spitalfields, London. This research confirms the
      results of an earlier study (Hoppa and Saunders [1998] J. Forensic. Sci. 43:174
      177) and extends it with the application of two new metric traits and further
      analyses of sex differences. Analyses of variance showed that SCTCH and AFTAL are
      significantly associated (P < 0.001) with rib number. Tukey tests of pairwise rib
      comparisons revealed that for two dimensions (SCTCH and AFTAL), the central ribs
      (3rd-6th) are significantly distinct from each other (P < 0.05). Using simple
      ranking of either the SCTCH or AFTAL traits, the proportion of correctly
      identified ribs within +/-1 position was 80%, compared to initial seriation using
      morphological methods (Dudar [1993] J. Forensic. Sci. 28:788-797; Mann [1993] J.
      Forensic. Sci. 28:151-155). Significant sex dimorphism was also identified for
      these two traits. Analysis of the HAFL trait produced somewhat equivocal results,
      suggesting that this variable is not reliable for rib seriation. The variable
      SCTCH proves to be the most useful dimension for seriation, and shows that all
      but the 7th-9th ribs can be distinguished from others in the sequence, with
      important results for the 4th rib, where ranking allowed identification in 86% of
      cases, consistent with morphological methods for intact ribs.

PMID- 15503342
TI  - Comparative postcranial body shape and locomotion in Chlorocebus aethiops and
      Cercopithecus mitis.
AB  - Body weight and length, chest girth, and seven postcranial limb segment lengths
      are compared between two guenon species, Chlorocebus (Cercopithecus) aethiops
      (vervets) and Cercopithecus mitis (blue monkeys), exhibiting different habitual
      locomotor preferences. The subjects, all adults, were wild caught for a non
      related research project (Turner et al. [1986] Genetic and morphological studies
      on two species of Kenyan monkeys, C. aethiops and C. mitis. In: Else JG, Lee PC,
      editors. Primate evolution, proceedings of the Xth International Congress of
      Primatology, Cambridge. London). The morphological results are interpreted within
      the context of previously published observations of primate locomotion and social
      organization. The sample is unique in that the body weight of each individual is
      known, allowing the effects of body-size scaling to be assessed in interspecific
      and intersexual comparisons. C. mitis has a significantly (P < 0.05) greater body
      weight and trunk length than C. aethiops. A shorter trunk may function to reduce
      spinal flexibility for ground-running in the latter. Proximal limb segments (arm
      and thigh) are significantly greater in C. mitis, reflecting known adaptations to
      committed arboreal quadrupedal locomotion. By contrast, relative distal limb
      segments (forearm, crus, and foot) are significantly longer in C. aethiops,
      concordant with a locomotor repertoire that includes substantial terrestrial
      quadrupedalism, in addition to arboreal agility, and also the requisite
      transition between ground and canopy. Although normally associated with arboreal
      monkeys, greater relative tail length occurs in the more terrestrial vervets.
      However, because vervets exploit both arboreal and terrestrial habitats, a longer
      tail may compensate for diminished balance during arboreal quadrupedalism
      resulting from the greater "brachial" and "crural" indices that enhance their
      ground quadrupedalism. Most interspecific differences in body proportions are
      explicable by differences in locomotor modalities. Some results, however,
      contradict commonly held "tenets" that relate body size and morphology
      exclusively to locomotion. Generally associated with terrestriality, sexual
      dimorphism (male/female) is greater in the more arboreal blue monkeys. A more
      intense, seasonal mating competition may account for this incongruity.

PMID- 15503343
TI  - Evaluation of intrarenal oxygenation by BOLD MRI at 3.0 T.
AB  - PURPOSE: To examine the benefit of using higher field strengths for BOLD MRI to
      detect changes in renal medullary oxygenation following pharmacological
      maneuvers. MATERIALS AND METHODS: Renal BOLD MRI, primarily at 1.5 T, has been
      shown to be useful for monitoring changes in medullary oxygenation status. We
      performed the present studies on a 3.0 T scanner using a multiple gradient-echo
      (mGRE) sequence with a multicoil array to acquire 16 T2*-weighted images within a
      single breath-hold. Data were obtained before and after administration of
      furosemide (20 mg iv). RESULTS: The baseline renal R2* (mean +/- SE) at 3.0 T was
      37.4+/-1.2 Hz in the medulla, and 21.8 +/- 1.2 Hz in the cortex. The BOLD
      response to furosemide (DeltaR2*) at 3.0 T was 11.8 +/- 1.1 Hz in the medulla,
      and 3.0 +/- 0.5 Hz in the cortex. CONCLUSION: Higher magnetic field strength is
      beneficial for renal BOLD MRI studies. The cortico-medullary contrast on the R2*
      map was significantly improved at 3.0 T, with no evidence of increased bulk
      susceptibility artifacts. Baseline R2* and DeltaR2* in the renal medulla at 3.0 T
      were both significantly higher compared to our previously reported data obtained
      at 1.5 T.

PMID- 15503344
TI  - Microevolution in prehistoric Andean populations: chronologic mtDNA variation in
      the desert valleys of northern Chile.
AB  - Archeological evidence suggests that the iconographic and technological
      developments that took place in the highlands around Lake Titicaca in the Central
      Andean region had an influence on the cultural elaborations of the human groups
      in the valleys and the Pacific coast of northern Chile. In a previous
      communication, we were able to show, by means of a distance analysis, that a
      craniofacial differentiation accompanied the process of cultural evolution in the
      valleys (Rothhammer and Santoro [2001] Lat. Am. Antiq. 12:59-66). Recently,
      numerous South Amerindian mtDNA studies were published, and more accurate
      molecular techniques to study ancient mtDNA are available. In view of these
      recent developments, we decided 1) to study chronological changes of ancient
      mtDNA haplogroup frequencies in the nearby Lluta, Azapa, and Camarones Valleys,
      2) to identify microevolutionary forces responsible for such changes, and 3) to
      compare ancient mtDNA haplogroup frequencies with previous data in order to
      validate craniometrical results and to reconstruct the biological history of the
      prehistoric valley groups in the context of their interaction with culturally
      more developed highland populations. From a total of 97 samples from 83
      individuals, 68 samples (61 individuals) yielded amplifications for the fragments
      that harbor classical mtDNA markers. The haplogroup distribution among the total
      sample was as follows: 26.2%, haplogroup A; 34.4%, haplogroup B; 14.8%,
      haplogroup C; 3.3%, haplogroup D; and 21.3%, other haplogroups. Haplogroup B
      tended to increase, and haplogroup A to decrease during a 3,900-year time
      interval. The sequence data are congruent with the haplogroup analysis. In fact,
      the sequencing of hypervariable region I of 30 prehistoric individuals revealed
      43 polymorphic sites. Sequence alignment and subsequent phylogenetic tree
      construction showed two major clusters associated with the most common
      restriction haplogroups. Individuals belonging to haplogroups C and D tended to
      cluster together with nonclassical lineages.

PMID- 15503345
TI  - Magnetic resonance imaging of knee cartilage using a water selective balanced
      steady-state free precession sequence.
AB  - PURPOSE: To compare an optimized water selective balanced steady-state free
      precession sequence (WS-bSSFP) with conventional magnetic resonance (MR)
      sequences in imaging cartilage of osteoarthritic knees. MATERIALS AND METHODS:
      Flip angles of sagittal and axial WS-bSSFP sequences were optimized in three
      volunteers. Subsequently, the knees of 10 patients with generalized
      osteoarthritis were imaged using sagittal and axial WS-bSSFP and conventional MR
      imaging techniques. We calculated contrast-to-noise ratios (CNR) between
      cartilage and its surrounding tissues to quantitatively analyze the various
      sequences. Using dedicated software we compared, in two other patients, the
      accuracy of cartilage volume measurements with anatomic sections of the tibial
      plateau. RESULTS: CNRtotal eff (CNR efficiency between cartilage and its
      surrounding tissue) using WS-bSSFP was maximal with a 20-25 degrees flip angle.
      CNRtotal eff was higher in WS-bSSFP than in conventional images: 6.1 times higher
      compared to T1-weighted gradient echo (GE) images, 5.1 compared to proton-density
      (PD) fast spin echo (FSE) images, and 4.8 compared to T2-weighted FSE images. The
      mean difference of cartilage volume measurement on WS-bSSFP and anatomic sections
      was 0.06 mL compared to 0.24 mL for T1-GE and anatomic sections. CONCLUSION: A WS
      bSSFP sequence is superior to conventional MR imaging sequences in imaging
      cartilage of the knee in patients with osteoarthritis.

PMID- 15503346
TI  - Effective blood signal suppression using double inversion-recovery and slice
      reordering for multislice fast spin-echo MRI and its application in simultaneous
      proton density and T2 weighted imaging.
AB  - PURPOSE: To design a multislice double inversion-recovery fast spin-echo (FSE)
      sequence, with k-space reordered by inversion time at slice position (KRISP)
      technique, to produce black-blood vessel wall magnetic resonance imaging (MRI).
      MATERIALS AND METHODS: In this sequence, central k-space sampling for each slice
      is required at inversion time (TI) of the blood signal. To fill the entire k
      space, the peripheral lines are obtained less or greater the TI and using a
      rotating slice order. Blood flow signal suppression was first evaluated using a
      phantom. Simulation studies were used to investigate FSE image quality. The final
      sequence was then applied to the rabbit abdominal aorta MRI at 4.7 T. RESULTS: In
      the flow phantom study, artifacts from slow-flowing water were substantially
      reduced by the KRISP technique; residual water spins were dephased by the strong
      phase-encoding gradient required for peripheral k-space. These dephased spins
      flowed into the slice plane where the center of k-space was being acquired at the
      TI of the flowing water signal. Multislice black-blood MR images were
      successfully obtained in the rabbit abdomen using the sequence with the k
      trajectory optimized by the simulation study. CONCLUSION: The KRISP technique was
      effective both in multislice double inversion-recovery FSE and in blood signal
      suppression.

PMID- 15503347
TI  - Relationship between vertebral bone marrow blood perfusion and common carotid
      intima-media thickness in aging adults.
AB  - PURPOSE: To evaluate the relationship between vertebral marrow blood perfusion
      and common carotid intima-media thickness (IMT) in aging adults. MATERIALS AND
      METHODS: An age- and sex-matched case control study was conducted. Subjects were
      contacted and enrolled voluntarily according to a database containing 2,258 cases
      that received carotid ultrasonography examination at our hospital in the previous
      two years. Forty-three pairs of subjects (56 male, 30 female; aged 44-85 years,
      average 63 years) underwent dynamic contrast-enhanced magnetic resonance (MR)
      study of the lumbar spine. The average peak enhancement percentage of the second
      to fourth lumbar vertebrae was used to represent the vertebral marrow perfusion
      status for each subject. The common carotid IMT, presence of plaque, peak
      enhancement percentage, body mass index (BMI), systolic and diastolic blood
      pressure, serum total cholesterol, high-density lipoprotein (HDL), and
      triglycerol levels were acquired for statistical analysis. RESULTS: The average
      peak enhancement percentage was significantly lower in thickened IMT group
      compared to the normal IMT group (73 +/- 23 vs. 90 +/- 27, P=0.0023). The carotid
      IMT inversely correlated with vertebral peak enhancement percentage (r=-0.33,
      P=0.0018). The vertebral peak enhancement percentage was significantly lower in
      subjects with presence of any carotid plaque (P=0.032). Common carotid IMT was
      the only significant variable that was negatively associated with vertebral
      marrow perfusion after adjusting for the effect of sex, age, blood pressure, BMI,
      total cholesterol, HDL, and triglycerol level in linear regression model
      (P=0.008). CONCLUSION: Our data demonstrate the negative association between
      vertebral marrow blood perfusion and common carotid IMT. These results suggest
      that common carotid IMT may provide the information of tissue perfusion status of
      the vertebral bone marrow.

PMID- 15503348
TI  - Respiratory reordered UNFOLD perfusion imaging.
AB  - PURPOSE: To propose a respiratory reordered UNFOLD (RR-UNFOLD) imaging sequence
      to significantly reduce the amount of k-space data required for first-pass MR
      myocardial perfusion imaging. MATERIALS AND METHODS: Rapid acquisition of high
      resolution imaging data is essential to detailed quantitative analysis of first
      pass myocardial perfusion. Existing MR sequences have explored the full capacity
      of the imaging hardware to reduce the acquisition window within each cardiac
      cycle while maintaining the desired spatial resolution. Further improvement in
      perfusion imaging will require a more efficient use of the information content of
      the k-space data. The method uses prospective diaphragmatic navigator echoes to
      ensure that temporal filtering of UNFOLD is carried out on a series of images
      that are spatially registered. An adaptive real-time rebinning algorithm is
      developed for the creation of static image subseries related to different levels
      of respiratory motion. Issues concerning the temporal smoothing of tracer kinetic
      signals are discussed, and a solution based on oversampling of the central k
      space is provided. The method is assessed in 10 normal subjects without the
      administration of contrast agent, and further validated by administration of Gd
      DTPA in 10 patients at rest. RESULTS: The results of this study show that RR
      UNFOLD significantly extends the applicability of UNFOLD to perfusion imaging,
      which yields a 40% reduction in image artifact when the same amount of k-space
      information is used. CONCLUSION: The scan efficiency achieved can be used in
      combination with MR hardware improvements for extending the three-dimensional
      spatial coverage and shortening the data acquisition window to provide detailed
      information on regional myocardial perfusion abnormalities.

PMID- 15503349
TI  - Dynamic near-real-time magnetic resonance imaging for analyzing the
      velopharyngeal closure in comparison with videofluoroscopy.
AB  - PURPOSE: To demonstrate the feasibility of dynamic magnetic resonance imaging
      (MRI) with near-real-time temporal resolution ("real-time MRI") for analyzing the
      velopharyngeal closure in comparison with multiview videofluoroscopy. MATERIALS
      AND METHODS: Seven patients (three females and four males, 5-21 years old, mean
      age=11.3 years) with suspected velopharyngeal insufficiency, and one healthy
      volunteer were examined with videofluoroscopy and real-time MRI using a turbo
      spin-echo (TSE) sequence (TR=170 msec, TE=21 msec, slice thickness=6 mm, six
      images per second). Imaging was done during phonation in all three image planes.
      The results were analyzed by two radiologists in comparison with videofluoroscopy
      as the standard of reference for overall image quality and the pattern of
      velopharyngeal closure. RESULTS: Real-time MRI correctly depicted the pattern of
      velopharyngeal closure in correspondence to videofluoroscopy in all cases.
      Concerning the movement of the pharyngeal walls, real-time MRI falsely depicted a
      general movement of the dorsal pharyngeal wall in one case, whereas
      videofluoroscopy showed no movement. In one patient, real-time MRI provided
      additional information by showing an asymmetric movement of the lateral
      pharyngeal walls that could not be depicted by videofluoroscopy due to technical
      limitations. Concerning image quality, the coronal plane was more difficult to
      evaluate with real-time MRI compared to videofluoroscopy. The axial plane was
      easier to analyze in real-time MRI compared to videofluoroscopy. CONCLUSION: Real
      time MRI has the potential to depict the pattern of velopharyngeal closure in
      close correlation with videofluoroscopy, and may deliver additional information
      in selected cases.

PMID- 15503350
TI  - Pancreatic sarcoidosis: MRI features.
AB  - Pancreatic sarcoidosis is a rare entity, and few reports in the literature
      describe the CT aspects of the disease. We report the MR features of a
      pathologically-confirmed case of pancreatic sarcoidosis, which presented as
      multiple pancreatic masses with low signal intensity on T1-weighted images, mild
      high signal intensity on T2-weighted images, and decreased enhancement compared
      to the normal pancreas after administration of gadolinium. Pancreatic sarcoidosis
      should therefore be included in the differential diagnosis of multiple pancreatic
      masses with these MRI features.

PMID- 15503351
TI  - Effects of albaconol from the basidiomycete Albatrellus confluens on DNA
      topoisomerase II-mediated DNA cleavage and relaxation.
AB  - The effect of albaconol on the growth of human tumor cell, DNA topoisomerase
      (topo)-mediated DNA cleavage and direct DNA breakage was investigated. Albaconol
      inhibited significantly the growth of the human tumor cell lines K562, A549, BGC
      823 and Bcap-37, the IC5s values were 7.99 +/- 0.4, 3.17 +/- 0.89, 4.18 +/- 0.14
      and 7.45 +/- 2.5 microM, respectively. Albaconol stabilized and increased the
      topo 11-mediated DNA cleavable complex and inhibited the religation activity of
      topo II in a dose-dependent manner, but it failed to affect the activity of topo
      I. Albaconol directly broke pBR322 DNA at high concentrations, but there was no
      effect on the macromolecule of K562 cells. These results strongly suggest that
      albaconol targeted specifically to DNA topo II and that this is one of the
      mechanisms of its antitumor action; the direct action of albaconol on DNA may
      partly contribute to its anti-tumor activity at high concentrations.

PMID- 15503352
TI  - Cinnamaldehyde and 2-methoxycinnamaldehyde as NF-kappaB inhibitors from
      Cinnamomum cassia.
AB  - Nuclear factor (NF)-cB is a transcription factor regulating the expression of
      inflammatory and immune genes. In the present study, an extract from stem bark of
      Cinnamomum cassia Blume(Lauraceae) was discovered to have an inhibitory effect on
      LPS-induced NF-KB transcriptional activity, which was determined using
      macrophages RAW 264.7 transfected stably with an alkaline phosphatase reporter
      construct containing four copies of the NF-KB binding KB sequence. Following
      activity-guided fractionation, trans-cinnamaldehyde and 2-methoxycinnamaldehyde
      were identified as the NF-KB inhibitors from C cassia with IC50 values of 43 MM
      and 31 pM, respectively. As a positive control, caffeic acid phenethyl ester
      (CAPE) showed an IC50 value of 2 uM on NF-KB transcriptional activity. Both trans
      cinnamaldehyde and 2-methoxycinnamaldehyde inhibited LPS-induced DNA binding
      activity of NF-KB in addition to NF-KB transcription-al activity.

PMID- 15503354
TI  - Phenolic compounds from Baseonema acuminatum leaves: isolation and antimicrobial
      activity.
AB  - Three new phenolic compounds, 1-galloyl-beta-D-glucopyranosyl-(1-->4)-beta-D
      galactopyranoside (1), 2-methoxy-5-(1 '2 3'-trihydroxypropyl)-phenyl- 1-0-(6"
      galloyl)-beta-D-glucopyranoside (2),and 2-methoxy-5-hydroxymethyl-phenyl-1-O-(6"
      galloyl)-beta-D-glucopyranoside (3), together with the known compounds benzyl 6'
      O-galloyl-beta-D-glucopyranoside (4), 1,6-di-O-galloyl-beta-D-glucopyranose (5),
      myrciaphenone B (6), kaempferol 3-0-(6"-galloyl)-beta-D-glucopyranoside (7),
      quercetin 3-0-(6"-galloyl)-beta-D-glucopyranoside (8), vomifoliol 9-O-beta-D
      apiofuranosyl-(1-->6)-beta-D-glucopyranoside, 2,3-dihydrobenzofuran-2-(4'-hydroxy
      3'-methoxyphenyl)-3-alpha-L-rhamnopyranosyloxymethyl-7-methoxy-5-propanol, and
      benzyl-O-alpha-L-rhamnopyranosyl-(1-->6)-Beta-D-glucopyranoside were isolated
      from the leaves of Baseonema acuminatum P. Choux (Asclepiadaceae). Their
      structures were determined by 1D- and 2D-NMR spectroscopy and by ESI-MS analysis.
      The antimicrobial activity of all compounds was evaluated in vitro against
      bacteria (Staphylococcus aureus two strains, Bacillus cereus, Bacillus subtilis,
      Escherichia coli, Salmonella thyphimurium) and three strains of Candida albicans.
      The new compounds 2 and 3, together with the known compound 4, showed antifungal
      activity against two clinically isolated Candida albicans strains and against C.
      albicans ATCC 2091; MIC values were in the range of 25-100 microg/mL. Compound 5
      was active against the two clinically isolated strains of C. albicans with MICs
      of 12.5 microg/mL and 25 microg/mL. Compounds 1, 6, 7, and 8 inhibited only one
      strain of C albicans at the maximum concentration used. None of the phenolic
      compounds tested was active against the bacteria studied.

PMID- 15503353
TI  - A new sesquiterpene-coumarin ether and a new abietane diterpene and their effects
      as inhibitors of P-glycoprotein.
AB  - A new sesquiterpene-coumarin ether (5'beta,9'alpha,10'alpha)-7-0-(3alpha-methoxy
      8'(12')-drimen-11'-yl)-scopoletin, designated driportlandin (1) and a new
      abietane quinoid diterpene 16-hydroxy-abieta-8,12-diene-11,14-dione, named
      portlanquinol (2) together with lupeol, nepehinol, wrightial, formonetin and
      davidigenin were isolated and characterized from the Me2CO extract of whole dried
      plant of Euphorbia portlandica. The structures of the new compounds were
      elucidated from spectral data including 2D-NMR experiments of COSY, HMQC, HMBC
      and NOESY. When examined for their effects on the reversal of multidrug
      resistance(MDR) on mouse lymphoma cells, compound 1 proved to be more active than
      the positive control verapamil and compound 2 was found to be toxic. This is the
      first report on the isolation of a sesquiterpene-coumarin and a quinoid-type
      diterpenoid from Euphorbia.

PMID- 15503355
TI  - In vitro antiviral diterpenes from the Brazilian brown alga Dictyota pfaffii.
AB  - Specimens of Dictyota pfaffii from Atol das Rocas, Northeast Brazil, afforded the
      rare dolabellane diterpene 10,18-diacetoxy-8-hydroxy-2, 6-dolabelladiene (1) and
      the new 10-acetoxy-8,18-di-hydroxy-2,6-dolabelladiene (2). Reduction of 1 yielded
      8,10,18-trihydroxy-2,6-dolabelladiene (3), also present in the crude ex-tract of
      D. pfaffii. All three structures were assigned by 1D and 2D NMR spectral data.
      These substances showed strong anti-HSV-1 activity in vitro but only 3 inhibited
      the reverse transcriptase enzyme of HIV-1.

PMID- 15503357
TI  - A new seco-abietane-type diterpene from the stem bark of Picea glehni.
AB  - A new seco-abietane-type diterpenoid, 13S-hydroxy-9-oxo-9,10-seco-abiet-8(14)-en
      18,10alpha-olide (1) along with a known lignan compound, pinoresinol (2) was
      isolated from the stem bark of Picea glehni (Fr. Schm.) Masters. Spectroscopic
      methods and chemical conversions were used to establish the structure of 1. In
      order to assess their cancer chemopreventive potential, the inhibition of Epstein
      Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol
      13-acetate (TPA) was examined for compound 1, its synthetic analogue, 9,10-seco
      8S,13S-epoxy-abiet-8(14)-en-18,10alpha-olide (la) and 2. The inhibitory effect of
      la on EBV-EA induction was strong (0, 20.7, 67.1 and 89.2 % inhibition at 1000,
      500,100 and 10 mol ratio/TPA). The IC50 of la was 226 mol ratio/32 pmol/TPA.

PMID- 15503356
TI  - Tucumanin, a beta-hydroxy-gamma-lactone bistetrahydrofuranic acetogenin from
      Annona cherimolia, is a potent inhibitor of mitochondrial complex I.
AB  - A new beta-hydroxy-gamma-methyl-gamma-lactone bistetrahydrofuranic acetogenin,
      tucumanin, with the infrequent symmetrical threo/trans/threo/trans/threo relative
      configuration at the tetrahydrofuran rings was isolated from Annona cherimolia
      (Annonaceae) seeds. The inhibitory potency on the mitochondrial complex I of
      acetogenins with this relative configuration (tucumanin and asimicin)was compared
      with that shown by the corresponding pairs with an asymmetrical
      threo/trans/threo/trans/erythro relative configuration
      (laherradurin/rolliniastatin-2, and itrabin/molvizarin). All these compounds act
      as selective inhibitors of mitochondrial complex I in the 0.18 - 1.55 nM range.

PMID- 15503358
TI  - Cutaneous adenocarcinoma metastases associated with swelling of the neck and
      cheeks.

PMID- 15503359
TI  - Dermatomyositis associated with acute myeloid leukaemia: a paraneoplastic
      association or a drug-induced phenomenon?

PMID- 15503360
TI  - Necrotizing sialometaplasia: a case report.

PMID- 15503361
TI  - Homozygous palmoplantar keratoderma type bothnia improved by erythromycin: a case
      report.

PMID- 15503362
TI  - Presence of Demodex in follicular hyperkeratotic spicules on the face. A casual
      association?

PMID- 15503363
TI  - Coexistence of congenital linear punctate keratoderma and nevus depigmentosus
      with lentigines: a case of twin spotting?

PMID- 15503364
TI  - Eczema infantum and its prognosis.

PMID- 15503365
TI  - Leukaemia cutis developing in a pressure ulcer.

PMID- 15503366
TI  - An atypical presentation of lymphomatoid papulosis.

PMID- 15503367
TI  - Skin necrosis after injection of PEG-interferon alpha2b in an HCV-infected
      patient.

PMID- 15503369
TI  - Technological advances and clinical trends in MRI.

PMID- 15503368
TI  - Hemispherectomy procedures in children: haematological issues.
AB  - OBJECTS: In literature, excessive perioperative haemorrhage and related
      haemodynamic instability have been described as major risk factors in
      hemispherectomy. In this report we analyse the impact of neurosurgical operation
      on both the haematological and coagulative patterns of these children, especially
      focusing on younger patients. METHODS: From 1993 to 2003, 18 consecutive children
      suffering from intractable epilepsia and treated by hemispherectomy were admitted
      to the Pediatric Intensive Care Unit (PICU) of Catholic University Medical
      School, Policlinico Gemelli, Rome. Eight children had an entire hemisphere
      removed (anatomical hemispherectomy), whereas the remaining 10 underwent
      disconnective procedures (functional hemispherectomy) or cerebral cortex
      ablations (e.g. hemicorticectomy). Eleven out of these 18 children underwent
      hemispherectomy because of hemimegalencephaly (HME): their mean age was 14.5
      months (range 3-56 months); non-HME patients underwent surgery for epileptogenic
      lesions involving the cerebral hemisphere to a great extent or diffusely. Data
      have been compared with an historical cohort of 13 children operated on before
      1992 at the same institution comparable for age, aetiology of epilepsy and the
      modalities of surgical operation. CONCLUSIONS: Blood losses and haemotransfusions
      showed a profound influence on the haematologic/coagulative status of the
      children operated upon. A strict correlation was demonstrated between estimated
      red cell volume (ERCV) loss and haemostatic impairment in this series. Recent
      surgical techniques appear to reduce blood losses and related haemocoagulative
      risks even in younger patients.

PMID- 15503370
TI  - MultiHance in brain tumor imaging.

PMID- 15503371
TI  - MultiHance in brain perfusion.

PMID- 15503372
TI  - MultiHance in multiple sclerosis: update of a study in progress.

PMID- 15503373
TI  - MultiHance in liver lesion detection: personal experience.

PMID- 15503374
TI  - MultiHance-enhanced MRI in the characterisation of focal liver lesions.

PMID- 15503375
TI  - MR-based assessment of potential living related liver donors.

PMID- 15503376
TI  - MR angiography with MultiHance for imaging the supra-aortic vessels.

PMID- 15503377
TI  - MultiHance in body MR angiography: personal experiences.

PMID- 15503378
TI  - MultiHance in MRA of peripheral vasculature.

PMID- 15503379
TI  - MultiHance for dynamic MR imaging of the breast.

PMID- 15503380
TI  - MultiHance in cardiac magnetic resonance imaging.

PMID- 15503381
TI  - 3D MR colonography after intravenous administration of the hepatobiliary contrast
      agent Gd-BOPTA: bile tagging.

PMID- 15503382
TI  - MultiHance and state-of-the-art contrast-enhanced MRI.

PMID- 15503383
TI  - Herbaceous covers to control tree invasion in rights-of-way: ecological concepts
      and applications.
AB  - In northeastern America, thousands of kilometers of utility rights-of-way (ROWs)
      have to be managed to prevent the establishment of a tall vegetation cover that
      does not comply with safety and maintenance regulations. Recent decades have seen
      the emergence of ecologically based vegetation control strategies to reduce
      environmental impacts as well as maintenance costs. One such strategy is to take
      advantage of competitive herbaceous covers to limit tree invasion. This approach,
      however, as well as its fundamental underlying principles, has been little
      scrutinized. In this article, (1) we present the main ecological concepts
      supporting the use of a herbaceous cover to limit tree invasion, emphasizing
      naturally forested ecosystems of northeastern America. They include reported
      evidence of stable plant communities and an overview of potential underlying
      mechanisms of inhibition. (2) We then review field applications, specifically
      testing the ability of seeded herbaceous covers to control tree invasion in ROWs.
      (3) We discuss unresolved issues relevant to management and research. The
      available evidence suggests that seeding herbaceous covers in ROWs can help
      control tree invasion, but many issues still limit broad-scale applications. The
      various interactions that govern plant community dynamics are far from being
      fully understood, so selecting species still largely depends on an empirical
      approach. Patterns of resistance to tree invasion must be investigated over a
      wide range of spatial, historical, and environmental contexts to determine
      effective management and seeding practices that will lead to broad-scale
      applications. We suggest establishing communities rather than single dominant
      species and using as much as possible native species to limit risks of invasion.

PMID- 15503384
TI  - Forest health, collective behaviors, and management.
AB  - This study compares community-based managed forests under different purposes of
      management, namely, state-driven "conservation" or community-designed utilization
      in two villages located in the Sopsai watershed, Nan Province, northern Thailand.
      The forest health under different intensity of uses is assessed in association
      with the collective behaviors and long-term purposes embedded in village social
      cultural context. The study found no significant differences in forest succession
      and proportion in diameter at 1.3 m (dbh) class and height-class distribution of
      the forest under different use intensity. The forest for utilization also showed
      higher density and basal area of the local preferred species than the
      "conservation" forest. In the utilization forest, we also found a higher number
      of multipurpose and preferred species than in the "conservation" forest, which
      actually responded to the needs of the community in the long term to have more
      wood products (both firewood and timbers). The community-based forest management
      (CBFM) for utilization can also lead to natural regeneration and biodiversity
      similar to "conservation" forests. Through CBFM, forest resources can be managed
      to maintain the healthy condition under different intensities and respond to both
      community needs and external expectation. The findings also emphasize the
      importance of recognizing community needs and management objectives in watershed
      restoration and improving the productivity of forests under collective
      management.

PMID- 15503385
TI  - Effect of human activities on overall trend of sedimentation in the lower Yellow
      River, China.
AB  - The Yellow River has been intensively affected by human activities, particularly
      in the past 50 years, including soil-water conservation in the upper and middle
      drainage basin, flood protection in the lower reaches, and flow regulation and
      water diversion in the whole drainage basin. All these changes may impact
      sedimentation process of the lower Yellow River in different ways. Assessing
      these impacts comprehensively is important for more effective environmental
      management of the drainage basin. Based on the data of annual river flow,
      sediment load, and channel sedimentation in the lower Yellow River between 1950
      and 1997, the purpose of this paper is to analyze the overall trend of channel
      sedimentation rate at a time scale of 50 years, and its formative cause. It was
      found in this study that erosion control measures and water diversion have
      counteractive impacts on sedimentation rate in the lower Yellow River. Although
      both annual river flow and sediment decreased, there was no change in channel
      sedimentation rate. A regression analysis indicated that the sedimentation in the
      lower Yellow River decreased with the sediment input to the lower Yellow River
      but increased with the river flow input. In the past 30-40 years, the basin-wide
      practice of erosion and sediment control measures resulted in a decline in
      sediment supply to the Yellow River; at the same time, the human development of
      water resources that required river flow regulation and water diversion caused
      great reduction in river flow. The former may reduce the sedimentation in the
      lower Yellow River, but the reduction of river flow increased the sedimentation.
      When their effects counterbalanced each other, the overall trend of channel
      sedimentation in the lower Yellow River remained unchanged. This fact may help us
      to better understand the positive and negative effects of human activities in the
      Yellow River basin and to pay more attention to the negative effect of the
      development of water resources. The results of this study demonstrate that, if
      the overuse of river water cannot be controlled, the reduction of channel
      sedimentation in the lower Yellow River cannot be realized through the practice
      of erosion and sediment control measures.

PMID- 15503386
TI  - An ecophysiological study of plants growing on the fly ash deposits from the
      "Nikola Tesla-A" thermal power station in Serbia.
AB  - This ecophysiological research on the ash deposits from the "Nikola Tesla-A"
      thermal power station in Serbia covered 10 plant species (Tamarix gallica,
      Populus alba, Spiraea van-hauttei, Ambrosia artemisifolia, Amorpha fruticosa,
      Eupatorium cannabinum, Crepis setosa, Epilobium collinum, Verbascum phlomoides,
      and Cirsium arvense). This paper presents the results of a water regime analysis,
      photosynthetic efficiency and trace elements (B, Cu, Mn, Zn, Pb, and Cd) content
      in vegetative plant parts. Water regime parameters indicate an overall stability
      in plant-water relations. During the period of summer drought, photosynthetic
      efficiency (Fv/Fm) was low, ranging from 0.429 to 0.620 for all the species that
      were analyzed. An analysis of the tissue trace elements content showed a lower
      trace metal concentration in the plants than in the ash, indicating that heavy
      metals undergo major concentration during the combustion process and some are not
      readily taken up by plants. The Zn and Pb concentrations in all of the examined
      species were normal whereas Cu and Mn concentrations were in the deficiency
      range. Boron concentrations in plant tissues were high, with some species even
      showing levels of more than 100 microg/g (Populus sp., Ambrosia sp., Amorpha sp.,
      and Cirsium sp.). The presence of Cd was not detected. In general, it can be
      concluded from the results of this research that biological recultivation should
      take into account the existing ecological, vegetation, and floristic potential of
      an immediate environment that is abundant in life forms and ecological types of
      plant species that can overgrow the ash deposit relatively quickly. Selected
      species should be adapted to toxic B concentrations with moderate demands in
      terms of mineral elements (Cu and Mn).

PMID- 15503387
TI  - Waste management in Guangdong cities: the waste management literacy and waste
      reduction preferences of domestic waste generators.
AB  - A questionnaire survey was conducted in 2002 on 1365 households in two
      prefectural-level cities in the Pearl River Delta, Jiangmen and Zhongshan. Three
      groups of issues are covered in this paper: 1) waste management literacy,
      concerns, and public participation; 2) waste recycling practices and the
      potential for waste avoidance; and 3) public environmental literacy. This study
      confirms findings from previous surveys and provides new information on important
      issues such as imposing monetary charges on waste and environmental activities,
      littering, source separation programs (SSPs), and public participation and
      expectations in local waste management. Saving up recyclable materials for
      redemption in waste depots is commonly practiced in mainland China regardless of
      the level of development of a city, although at the household level, high-income
      families tend to place less value on the revenues to be gained from redemption
      than lower income groups do. Data from the previous and the present studies
      indicate that such voluntary but largely economically driven waste recovery
      behavior diverts at least 10% of the household waste from the waste stream.
      Although uncompensated SSP is less appealing in the two cities than compensated
      SSP, it was found that when the median per capita income of a city reaches
      RMB2000 per month, a high participation rate for uncompensated waste recovery is
      more likely to occur. Education and income levels are the chief factors affecting
      littering behavior and the potential for waste avoidance. Contrary to general
      belief, the local Chinese community is active in microwaste management. The
      concern, however, is over the inability of the grassroots bureaucracy to deal
      with rising expectations for waste collection services and neighborhood
      cleanliness.

PMID- 15503388
TI  - Environmental and economic factors can increase the risk of exotic species
      introductions to the Arctic region through increased ballast water discharge.
AB  - The effects of global warming can increase the risk of exotic species
      introductions in eastern Canadian Arctic waters by reducing surface ice cover and
      allow increased access to commercial vessels. Ballast water discharged by
      incoming overseas vessels is an important means for introducing species on a
      global scale. Analyses of air temperatures at Churchill, Manitoba between 1943
      and 2002 indicated an increase in mean temperature within the past decade.
      Churchill is the only major northern port in this region where grain has been
      exported on a limited basis due to the short navigation season. Economic analyses
      of grain exported from Canadian and U.S. ports indicated some cost advantages for
      using northern ports. The Hudson Bay region is vulnerable to increased exotic
      species introductions because of its southerly location. Current ballast water
      exchange measures to reduce the risk of introductions may not be effective
      because most vessels enter the region with ballast, and the ballast exchange zone
      is located relatively close to coastal areas where the habitat could be favorable
      for an introduced species to become established. The probability of a large crab
      species introduced to this region from northern European waters is discussed. The
      risk of ballast water-related exotic species introduction to this region may be
      reduced by expanding the types of cargo handled and developing a strong import
      market. This approach would accommodate an increase in the number of vessels with
      cargo, and substantially reduce the volume of ballast carried to this region.

PMID- 15503389
TI  - Contaminant exposure and effects in red-winged blackbirds inhabiting stormwater
      retention ponds.
AB  - Stormwater wetlands are created to retain water from storms and snow melt to
      reduce sediment, nutrient, and contaminant pollution of natural waterways in
      metropolitan areas. However, they are often a source of attractive habitat to
      wetland-associated wildlife. In this study of 12 stormwater wetlands and a
      larger, older reference site, elevated concentrations of zinc and copper were
      found in sediments and carcasses of 8-day-old red-winged blackbird (Agelaius
      phoeniceus) nestlings inhabiting stormwater sites. Although nesting success in
      the stormwater wetlands was comparable to national averages, sediment zinc
      concentrations correlated with clutch size, hatching success, fledgling success,
      and Mayfield nest success, suggesting that the nestlings may have been stressed
      and impaired by elevated zinc. This stress may have been direct on the nestlings
      or indirect through effects on the availability of food organisms.

PMID- 15503390
TI  - Using ecological risk assessment to identify the major anthropogenic stressor in
      the Waquoit Bay Watershed, Cape Cod, Massachusetts.
AB  - The Waquoit Bay Watershed ecological risk assessment was performed by an
      interdisciplinary and interagency workgroup. This paper focuses on the steps
      taken to formulate the analysis plan for this watershed assessment. The workgroup
      initially conducted a series of meetings with the general public and local and
      state managers to determine environmental management objectives for the
      watershed. The workgroup then decided that more information was needed on the
      impacts of six stressors: nutrient enrichment, physical alteration of habitat,
      altered freshwater flow, toxic chemicals, pathogens, and fisheries harvesting.
      Assessment endpoints were selected to establish the link between environmental
      management objectives, impacts of stressors, and scientifically measurable
      endpoints. The following assessment end-points were selected: estuarine eelgrass
      cover, scallop abundance, finfish diversity and abundance, wetland bird
      distribution and abundance, piping plover distribution and abundance, tissue
      contaminant levels, and brook trout distribution and abundance in streams. A
      conceptual model was developed to show the pathways between human activities,
      stressors, and ecological effects. The workgroup analyzed comparative risks, by
      first ranking stressors in terms of their potential risk to biotic resources in
      the watershed. Then stressors were evaluated by considering the components of
      stressors (e.g., the stressor chemical pollution included both heavy metals and
      chlorinated solvents components) in terms of intensity and extensiveness. The
      workgroup identified nutrient enrichment as the major stressor. Nutrient
      enrichment comprised both phosphorus enrichment in freshwater ponds and nitrogen
      enrichment within estuaries. Because phosphorus impacts were being analyzed and
      mitigated by the Air Force Center for Environmental Excellence, this assessment
      focused on nitrogen. The process followed to identify the predominant stressor
      and focus the analyses on nitrogen impacts on eelgrass and scallops will serve as
      an example of how to increase the use of the findings of a watershed assessment
      in decision making.

PMID- 15503391
TI  - Cumulative impacts of dock shading on Spartina alterniflora in South Carolina
      estuaries.
AB  - Salt marshes dominated by Spartina alterniflora and the associated networks of
      tidal creeks that drain them are characteristic geographical features of
      southeastern estuaries, important nursery habitat areas, and preferred sites for
      residential development. As the size of the coastal population increases, so has
      the number of requests for dock permits. With each new request for a dock permit,
      public concerns about the cumulative environmental impacts of dock proliferation
      on the coastal environment have increased. The objective of this particular study
      was to evaluate the impacts of shading by dock structures on stem densities of S.
      alterniflora in South Carolina coastal marshes. Shading impacts under individual
      docks were extrapolated to the tidal creek (local), county, and statewide scales.
      Dock structures were sampled both under and next to the walkway in the Charleston
      Harbor area of South Carolina. The density of S. alterniflora under docks was
      significantly lower than that which occurred next to the docks (i.e., 5 m away)
      for the short-form, tall-form, and both forms combined. We estimated that shading
      effects from dock structures in South Carolina decreased the stem density of S.
      alterniflora by 71%. Dock shading effects were small when evaluated from the
      perspective of the amount of marsh that occurs within specific tidal creeks (0.03
      0.72%), in coastal counties at a maximum dock length (0.01-0.98%), or statewide
      (0.01-0.13%) at a maximum dock length. However, approximately 7,000 docks have
      been permitted over the last decade, resulting in a loss of salt marsh equivalent
      to 60 ha.

PMID- 15503392
TI  - Use of radar remote sensing (RADARSAT) to map winter wetland habitat for
      shorebirds in an agricultural landscape.
AB  - Many of today's agricultural landscapes once held vast amounts of wetland habitat
      for waterbirds and other wildlife. Successful restoration of these landscapes
      relies on access to accurate maps of the wetlands that remain. We used C-band
      (5.6-cm-wavelength), HH-polarized radar remote sensing (RADARSAT) at a 38 degrees
      incidence angle (8-m resolution) to map the distribution of winter shorebird
      (Charadriiformes) habitat on agricultural lands in the Willamette Valley of
      western Oregon. We acquired imagery on three dates (10 December 1999, 27 January
      2000, and 15 March 2000) and simultaneously collected ground reference data to
      classify radar signatures and evaluate map accuracy of four habitat classes: (1)
      wet with < or = 50% vegetation (considered optimal shorebird habitat), (2) wet
      with > 50% vegetation, (3) dry with < or = 50% vegetation, and (4) dry with > 50%
      vegetation. Overall accuracy varied from 45 to 60% among the three images, but
      the accuracy of focal class 1 was greater, ranging from 72 to 80%. Class 4
      coverage was stable and dominated maps (40% of mapped study area) for all three
      dates, while coverage of class 3 decreased slightly throughout the study period.
      Among wet classes, class 1 was most abundant (about 30% coverage) in December and
      January, decreasing in March to approximately 15%. Conversely, class 2 increased
      dramatically from January to March, likely due to transition from class 1 as
      vegetation grew. This approach was successful in detecting optimal habitat for
      shorebirds on agricultural lands. For modest classification schemes, radar remote
      sensing is a valuable option for wetland mapping in areas where cloud cover is
      persistent.

PMID- 15503393
TI  - The origin of aromaticity: important role of the sigma framework in benzene.
AB  - The physical nature of aromaticity is addressed at a high ab initio level. It is
      conclusively shown that the extrinsic aromatic stabilization energy of benzene
      E(ease)B, estimated relative to its linear polyene counterpart(s), is very well
      reproduced at the Hartree-Fock (HF) level. This is a consequence of the fact that
      the contributions arising from the zero-point vibrational energy (ZPVE) and
      electron correlation are rather small. More specifically, they yield together 2.0
      kcalmol(-1) to the destabilization of benzene. A careful scrutiny of the HF
      energies by virial theorem shows further that the kinetic energies of the sigma
      and pi electrons E(T)HF(sigma) and E(T)HF(pi) are strictly additive in the gauge
      linear zig-zag polyenes, which also holds for their sum Et(T)HF This finding has
      the important corollary that E(ease)B is little dependent on the choice of the
      homodesmic reactions involving zig-zag polyenes. A detailed physical analysis of
      the sigma- and pi-electron contributions to extrinsic aromaticity requires
      explicit introduction of the potential energy terms Vne, Vee, and Vnn, which
      signify Coulomb interactions between the electrons and the nuclei. The Vee term
      involves repulsive interaction Vee(sigmapi) between the sigma and pi electrons,
      which cannot be unequivocally resolved into sigma and pi contributions. The same
      holds for the Vnn energy, which implicitly depends on the electron density
      distribution via the Born-Oppenheimer (BO) potential energy surface. Several
      possibilities for partitioning Vee(sigmapi) and Vnn terms into sigma and pi
      components are examined. It is argued that the stockholder principle is the most
      realistic, which strongly indicates that E(ease)B is a result of favorable sigma
      framework interactions. In contrast, the pi-electron framework prefers the open
      chain linear polyenes.

PMID- 15503394
TI  - Improving screening for alcohol use during pregnancy: the Massachusetts ASAP
      program.
AB  - OBJECTIVE: To motivate prenatal care staff in public and private settings to
      universally screen for risk of alcohol and drug use and to conduct a brief
      intervention with follow-up referral when appropriate during a routine office
      visit. METHODS: The ASAP Project methods were engagement of site staff; staff
      training; self-administered questionnaires embedded with a relational and broad
      catch screening tool; a brief intervention protocol; unique clinical decision
      tree/protocols for each site; identification of treatment and referral resources;
      and ongoing technical assistance and consultation. Sites were located in four
      regions of the state and included four community health centers, a network of
      multi-specialty private practices and a teaching hospital. RESULTS: Across 16
      sites, 118 prenatal staff were trained on use of the screening tool and 175 staff
      on the brief intervention. The ASAP Project resulted in 95% of pregnant women
      being screened for alcohol use and 77% of those screening positive for at least
      one risk factor receiving a brief intervention during a routine office visit.
      CONCLUSIONS: Screening and brief interventions for alcohol use can be delivered
      effectively within a routine prenatal care visit by prenatal staff by utilizing
      and building on existing office systems with practice staff, screening for any
      use not only at risk use, providing training with skills building sessions and
      information delivered by physicians, offering easy-to-access community treatment
      resources, and providing ongoing technical assistance.

PMID- 15503395
TI  - Enhancement of photodynamic therapy by use of aminolevulinic acid/glycolic acid
      drug mixture.
AB  - 5-aminolevulinic acid (5-ALA) is a precursor in synthesis of endogenous
      porphyrins used to sensitize tumor tissues in photodynamic therapy (PDT). It is
      administered topically into a tumor which after the certain time, required for
      porphyrins to accumulate, is irradiated with visible light from the proper source
      at established wavelength. Our main aim in the present study was to increase the
      penetration of 5-ALA through the skin and other tissues by addition of glycolic
      acid (GA) to 5-ALA on cell lines in vitro and on animals. We also applied 5-ALA
      ointment with glycolic acid to patients suffering from squamous cell carcinoma
      (SCC). In our study, we used 5-ALA, dimethyl sulfoxide (DMSO),
      ethylenediaminetetraacetic acid, disodium salt (EDTA) and GA together in one
      formulation (5-ALA-GA) on eucerin support. We compared both therapeutic and
      cosmetic effects in 5-ALA-GA-PDT and in control group of patients. Our results
      showed that modification of 5-ALA ointment by addition of 5% GA caused that the
      treated lesions responded with rapid regression. In 12 patients with single
      lesions of SCC type subjected to 5-ALA-GA-PDT, we observed 100% regression of
      tumors following single or repeated two-three times PDT. In vitro and in vivo in
      animals total porphyrin levels after addition of 5% GA increased significantly
      (P<0.01). These results provide evidence that addition of glycolic acid should be
      considered as the agent which enhances 5-ALA penetration in tissues and thus
      increases the effectiveness of photodynamic therapy.

PMID- 15503396
TI  - SARS transmission and commercial aircraft.

PMID- 15503397
TI  - Estimating SARS incubation period.

PMID- 15503398
TI  - Detecting bioterror attack.

PMID- 15503399
TI  - Aeromonas spp. and infectious diarrhea, Hong Kong.

PMID- 15503400
TI  - Trichinella papuae in saltwater crocodiles (Crocodylus porosus) of Papua New
      Guinea.

PMID- 15503401
TI  - Panton-Valentine leukocidin-positive Staphylococcus aureus, Singapore.

PMID- 15503402
TI  - Balamuthia amebic encephalitis risk, Hispanic Americans.

PMID- 15503403
TI  - SARS alert applicability in postoutbreak period.

PMID- 15503404
TI  - SARS outbreak in Taiwan.

PMID- 15503405
TI  - Toronto Emergency Medical Services and SARS.

PMID- 15503406
TI  - SARS during pregnancy, United States.

PMID- 15503407
TI  - Eosinophilic pleural effusion in gnathostomiasis.

PMID- 15503408
TI  - Methicillin-resistant Staphylococcus aureus, Pakistan, 1996-2003.

PMID- 15503409
TI  - Borrelia valaisiana in cerebrospinal fluid.

PMID- 15503410
TI  - Baylisascaris procyonis in California.

PMID- 15503411
TI  - Streptococcus iniae discitis in Singapore.

PMID- 15503412
TI  - Rubella epidemic strain, Greece, 1999.

PMID- 15503413
TI  - CTX-M beta-lactamase-producing Escherichia coli in long-term care facilities,
      France.

PMID- 15503414
TI  - Do antiborrelial antibodies suggest Lyme disease in Cuba?

PMID- 15503415
TI  - Human herpesvirus 6 encephalomyelitis.

PMID- 15503416
TI  - Vancomycin heteroresistance in methicillin-resistant Staphylococcus aureus,
      Taiwan.

PMID- 15503417
TI  - A US soldier who returned from Iraq with nonhealing sores.

PMID- 15503418
TI  - Malaria and HIV: interplay of risk.

PMID- 15503419
TI  - Going green saves over time.

PMID- 15503420
TI  - The air law payoff.

PMID- 15503421
TI  - North American birds and West Nile virus.

PMID- 15503422
TI  - John Maynard Smith (1920-2004).

PMID- 15503423
TI  - Assisted outpatient treatment for mental illness.

PMID- 15503424
TI  - Breaking down technological barriers.

PMID- 15503425
TI  - His tag effect on solubility of human proteins produced in Escherichia coli: a
      comparison between four expression vectors.
AB  - We have compared four different vectors for expression of proteins with N- or C
      terminal hexahistidine (His6) tags in Escherichia coli by testing these on 20
      human proteins. We looked at a total recombinant protein production levels per
      gram dry cell weight, solubility of the target proteins, and yield of soluble and
      total protein when purified by immobilized metal ion affinity purification. It
      was found that, in general, both N- and C-terminal His6 tags have a noticeable
      negative affect on protein solubility, but the effect is target protein specific.
      A solubilizing fusion tag was able to partly counteract this negative effect.
      Most target proteins could be purified under denaturing conditions and about half
      of the proteins could be purified under physiological conditions. The highest
      protein production levels and yield of purified protein were obtained from a
      construct with C-terminal His tag. We also observe a large variation in cell
      growth rate, which we determined to be partly caused by the expression vectors
      and partly by the targets. This variation was found to be independent of the
      production level, solubility and tertiary structure content of the target
      proteins.

PMID- 15503426
TI  - Etiology of increased enzymuria in different morphological forms of
      glomerulonephritis.
AB  - BACKGROUND: High urinary excretion of lysosomal enzymes is thought to reflect
      tubulointerstitial damage and is observed both in the acute and chronic phases of
      various morphological forms of glomerulonephritis (GN). It is related to the
      degree of proteinuria and secondary interstitial inflammatory process. N-acetyl
      beta-D-glucosaminidase (NAG) and beta-glucuronidase (beta-GR) are the most
      commonly used markers of tubulointerstitial injury. NAG and beta-GR are also
      contained in azurophilic granulations of polymorphonuclear leukocytes (PMNs) and
      may be released during the activation of PMNs. AIMS: The aim of this study was to
      elucidate the role of PMN degranulation in causing the increase of urinary
      excretion of lysosomal enzymes that is observed in glomerulonephritis. MATERIAL
      AND METHODS: We analyzed the urinary excretion of NAG, its B isoenzyme NAG-B,
      beta-GR and leukocyte elastase (EL), in 91 patients with morphologically
      different primary and secondary glomerulopathies, and in 12 healthy controls.
      RESULTS: Excretion of NAG, NAG-B and beta-GR were statistically significantly
      higher in all GN patients in comparison to healthy controls. In the whole
      analyzed GN population significant correlations between amount of proteinuria and
      excretion of NAG, NAG-B and beta-GR were ascertained. In subgroup analysis NAG
      excretion was significantly correlated with proteinuria in patients with diffuse
      proliferative GN (PGN), mesangiocapillary GN (MCGN), and minimal change disease
      (MCD). There was a significant correlation between NAG-B and proteinuria in MCD
      and PGN patients. There was a significant relationship of beta-GR and EL with
      proteinuria and EL with NAG in the PGN group. Significant relationships between
      serum creatinine and excretion of EL but not NAG, NAG-B, or beta-GR were observed
      in the whole examined group. CONCLUSIONS: Increased urinary excretion of
      elastase, with concomitant high proteinuria and NAG excretion in patients with
      proliferative GN may indicate that leukocyte degranulation is an additional
      source of enzymuria in the primary i.e. glomerular inflammatory process.
      Significant relationship between EL excretion and serum creatinine may indicate
      that EL released from PMN may also participate in the secondary i.e. interstitial
      injury that is decisive in the progression of GN.

PMID- 15503427
TI  - Abstracts of the IVth International Congress on Spondyloarthropathies. October 7
      9, 2004, Gent, Belgium.

PMID- 15503428
TI  - Tooth sensitivity associated with the use of luting cements.
AB  - Luting Cements are still a source of frustration to the dentist. None of the
      cements currently available satisfies everyone, including the patient. The
      problems encountered when trying to obtain adhesion to a wet substance such as
      dentin are well-known (Christensen, 1994). The cause of postcementation
      sensitivity continues to a perplexing problem.

PMID- 15503429
TI  - Posterior bite collapse: a review of concepts.

PMID- 15503430
TI  - Dentistry and CD4+ cell counts.

PMID- 15503431
TI  - Addressing the dental needs of the emerging geriatric population.

PMID- 15503432
TI  - Drug delivery to the brain--realization by novel drug carriers.
AB  - Delivery of drugs to the brain is still a major challenge. Successful delivery
      across the bloodbrain barrier has only been achieved in some cases, e.g., using
      pro-drugs. The review describes the delivery to the brain using nanoparticulate
      drug carriers in combination with the novel targeting principle of "differential
      protein adsorption" (PathFinder technology). The PathFinder technology exploits
      proteins in the blood which adsorb onto the surface of intravenously injected
      carriers for targeting. Apolipoprotein E is the targeting moiety for the delivery
      of particles to the endothelials of the blood-brain barrier. To reach therapeutic
      drug level in the brain, nanoparticulate drug carriers with sufficiently high
      loading capacity are reviewed, including drug nanocrystals (nanosuspensions),
      lipid drug conjugate (LDC) nanoparticles and lipid nanoparticles (solid lipid
      nanoparticles-SLN, nanostructured lipid carriers-NLC). The features are
      described, including regulatory aspects and large scale production.

PMID- 15503433
TI  - Influence of the surface properties on nanoparticle-mediated transport of drugs
      to the brain.
AB  - Poly(alkyl cyanoacrylate) nanoparticles enable the delivery of a number of drugs,
      including doxorubicin, loperamide, tubocurarine, the NMDA receptor antagonist MRZ
      2/576, and the peptides dalargin and kytorphin across the blood-brain barrier
      (BBB) after coating with surfactants. However, only the surfactants polysorbate
      (Tween) 20, 40, 60 and 80, and some poloxamers (Pluronic F 68) can induce this
      uptake. The mechanism for the delivery across the BBB most likely is endocytosis
      via the LDL receptor by the endothelial cells lining the brain blood capillaries
      after injection of the nanoparticles into the blood stream. This endocytotic
      uptake seems to be mediated by the adsorption of apolipoprotein B and/or E
      adsorption from the blood. Thus, the nanoparticles could mimic lipoprotein
      particles and act as "Trojan Horses." The drug, then, may be released either
      within these cells followed by passive diffusion into the brain or be transported
      into the brain by transcytosis.

PMID- 15503434
TI  - Nanoscale analysis of biofunctional molecules and components.
AB  - In basic medical research, as well as in concrete clinical applications, the
      nanoscale analysis of biofunctional units is of strongly increasing relevance.
      Dedicated investigations on molecules, molecular composites or functional units
      can efficiently be performed ex or in situ by scanning probe methods and, namely,
      by scanning force microscopy. In the following investigations, the folding
      behavior of DNA is presented as an example of basic research in medicine. In
      contrast, the investigation of bioadsorption phenomena in systems on which
      apheresis therapies are based provides a real contribution to applied medicine.

PMID- 15503435
TI  - Considerations on surface and structural biocompatibility as prerequisite for
      long-term stability of neural prostheses.
AB  - Neural prostheses are technical systems that partially substitute neural
      functions of the body after traumatic lesions or neurological disorders. Using
      biomedical microsystems, complex implants can be designed and fabricated in very
      small dimensions. However, miniaturization of neural prostheses for long-term
      implantation is very challenging. Implants not only have to be biosafe and
      biostable in terms of cytotoxicity and degradation, they also have to cope with
      the biological requirements of structural biocompatibility. In this paper,
      examples of biomedical microimplants for neural prostheses use are introduced.
      Results from basic biocompatibility investigations regarding the cytotoxicity are
      reported, as well as aspects of the interaction between surface structure and
      cell behaviour. A detailed outlook addresses possible approaches to use
      nanosciences to ensure long-term stability of thin technical layers within the
      body and create surfaces for selective and specified functional reactions at the
      interface between the artificial implant and the biological environment.

PMID- 15503436
TI  - Controlled surface functionalization of silica nanospheres by covalent
      conjugation reactions and preparation of high density streptavidin nanoparticles.
AB  - Silica nanoparticles with a diameter of 100 nm were covalently modified at their
      surface by adjustable amounts of amine and carboxyl functional groups.
      Bioconjugation studies of two proteins, streptavidin and streptactin, with the
      functional nanoparticles resulted in optimum binding of the proteins to a long
      chain carboxyl-terminated linker. The surface functionalization of the
      nanoparticles was monitored by a variety of independent methods, including zeta
      potential measurements, dynamic light scattering (DLS), scanning electron
      microscopy (SEM), particle charge detection titrations (PCD) and elemental
      analysis. At the surface of the nanoparticles, a functional surface group density
      of 1.8 amino groups per nm2 was realized. The amine functions were quantitatively
      transferred to carboxyl groups coupled with a linker elongation. Streptavidin was
      immobilized by covalent binding to the carboxyl linkers and resulted in a protein
      density at the surface of the nanoparticles that was three times higher than the
      highest binding densities at nanoparticles published to date. The binding
      capacity of the streptavidin-covered nanoparticles for ligand biotin was
      quantified by titration with biotin-4-fluorescein to 2.5 biotin binding sites per
      100 nm2.

PMID- 15503437
TI  - Polyplexes of polyethylenimine and per-N-methylated polyethylenimine-cytotoxicity
      and transfection efficiency.
AB  - For non-viral gene delivery, the carriers for DNA transfer into cells must be
      vastly improved. The branched cationic polymer polyethylenimine has been
      described as an efficient gene carrier. However, polyethylenimine was
      demonstrated to mediate substantial cytotoxicity. Therefore, this study is aimed
      at investigating per-N-methylated polyethylenimine, which is thought to have a
      much lower cytotoxicity due to its lower charge density. Results from a gel
      retardation assay and laser light scattering indicated that per-N-methylated
      polyethylenimine condenses DNA into small and compact nanoparticles with a mean
      diameter <150 nm. Furthermore, polyplexes of polyethylenimine and per-N
      methylated polyethylenimine with DNA had a positive zeta potential and the
      polymers protected DNA from nuclease-mediated digestion. The transfection
      efficiency of polyethylenimine and per-N-methylated polyethylenimine was tested
      in CHO-K1 cells. Using green fluorescent protein as reporter gene and flow
      cytometry analysis, we demonstrated that per-N-methylated polyethylenimine has a
      lower cytotoxicity, but also a significantly lower transfection efficiency. Using
      propidium iodide staining, we could additionally distinguish between viable and
      dead cells. At NP > or = 12, per-N-methylated polyethylenimine showed a much
      higher cell viability and the ratio of viable and transfected cells to dead and
      transfected cells was about 1.5 to 1.7 fold higher than for polyethylenimine. The
      results of cell viability from flow cytometry analysis were confirmed by the MTS
      assay. Using luciferase reporter gene for transfection experiments, the gene
      expression of per-N-methylated polyethylenimine was lower at NP 6, 12 and 18 as
      compared to polyethylenimine, but at NP 24 it yielded similar levels.

PMID- 15503438
TI  - Toxicological hazards of inhaled nanoparticles--potential implications for drug
      delivery.
AB  - Nanoparticles (NP), here defined as particles with a diameter smaller then 100
      nm, are increasingly used in different applications, including drug carrier
      systems and to pass organ barriers such as the blood-brain barrier. On the other
      hand, a large body of know-how is available regarding toxicological effects of
      nanoparticle (NP) after inhalation. More specifically, a number of effects of
      inhaled NP are attributed to their (i) direct effects on the central nervous
      system, (ii) their translocation from the lung into the bloodstream, and (iii)
      their capacity to invoke inflammatory responses in the lung with subsequent
      systemic effects. This paper gives a brief review on the toxicology of inhaled
      NP, including general principles and current paradigms to explain the special
      case of NP in pulmonary toxicology. Since the evidence for health risks of NP
      after inhalation has been increasing over the last decade, this paper tries to
      extrapolate these findings and principles observed in inhalation toxicology into
      recommendations and methods for testing NP for nanocarrier purposes. A large gap
      is present between research on NP in inhalation toxicology and in nanoscaled drug
      carrying. This review recommends a closer interaction between both disciplines to
      gain insight in the role of NP size and properties and their mechanisms of acute
      and chronic interaction with biological systems.

PMID- 15503439
TI  - Initial salivary pellicle formation on solid substrates studied by AFM.
AB  - Organic layers of salivary biopolymers adsorbed on soft and hard oral tissues,
      referred to also as salivary pellicle, play a critical role with respect to all
      surface phenomena taking place in the oral cavity. The initial stages of pellicle
      formation are of great interest since they determine the ensuing processes of
      salivary biopolymer adsorption and subsequent adherence of bacteria. In spite of
      the important physiological role of the pellicle in protecting the enamel surface
      against short-term acidic attacks, the composition and ultrastructure of the
      pellicle layer are not yet understood and resolved in detail. The present study
      utilized atomic force microscopy (AFM), for the first time, to elucidate the
      morphogenesis and ultrastructural pattern of initial salivary pellicle formation
      taking place in situ on solid substrates of mica, silicon wafer and graphite.
      Using tapping mode AFM, salivary pellicles were found in all intraorally exposed
      specimens and revealed a globular surface morphology of the adsorbed protein
      layer. The average diameter and height of the adsorbed salivary proteins were
      determined to be 15 +/- 3 nm and 2.0 +/- 0.5 nm, respectively. It was also found
      that the surface energy of the substrates affects the rate of pellicle formation,
      while the overall size of the adsorbed salivary proteins appears to be identical
      on all studied substrates.

PMID- 15503440
TI  - Synthesis and properties of plasma-polymerized polypyrrole/Au composite
      nanofibers.
AB  - Nanostructured composites have a wide variety of potential applications in
      microelectronics, chemical sensors, and electrochemical energy production. Here,
      we report the chemical, structural, and electrochemical characteristics of a
      nanostructured composite material formed from plasma-polymerized polypyrrole
      coated Au fibers. The properties of the plasma-polymerized polypyrrole (PPPy)
      films were characterized by FTIR, X-ray photoelectron spectroscopy (XPS), and UV
      Vis spectroscopy, as well as cyclic voltammetry (CV), and scanning electron
      microscopy (SEM). These spectroscopy analyses suggest that thermal treatment of
      the materials results in elimination of loosely-bound, low mass oligomers in the
      films. Mass spectral analysis of the plasma phase suggests that plasma
      polymerization of the pyrrole takes place on the substrate surface as a result of
      diffusion of radicals produced in the plasma. In addition, thermal treatment
      enhances the electrochemical properties of the PPPy films because of changes in
      the surface morphology and bulk structure of the films. However, as-deposited
      PPPy films coated on Au nanotubes demonstrate better electrochemical properties
      than as-deposited PPPy films coated on flat ITO electrodes as a result of the
      increase in surface area and decrease in film thickness.

PMID- 15503441
TI  - Dynamic scale theory for characterizing surface morphology of layer-by-layer
      films of poly(o-methoxyaniline).
AB  - The dynamic scale theory and fractal concepts are employed in the
      characterization of surface morphological properties of layer-by-layer (LBL)
      films from poly(o-methoxyaniline) (POMA) alternated with poly(vinyl sulfonic
      acid) (PVS). The fractal dimensions are found to depend on the procedures to
      fabricate the POMA/PVS multilayers, particularly with regard to the drying
      procedures. LBL films obtained via drying in ambient air show a more homogeneous
      surface, compared to films dried under vacuum or a flow of nitrogen, due to a
      uniform rearrangement of polymer molecules during solvent evaporation.

PMID- 15503442
TI  - Fabrication of multi-wall carbon nanotube film on glassy carbon electrode surface
      and the determination of tyrosine.
AB  - A novel chemically modified electrode has been prepared on the basis of the
      attachment of multi-wall carbon nanotubes (MWNT) onto the surface of a glassy
      carbon electrode (GCE) in the presence of a hydrophobic surfactant, dihexadecyl
      phosphate (DHP). This MWNT film was characterized by transmission electron
      microscopy images (TEM) and scanning electron microscopy (SEM). The
      electrochemical behavior of tyrosine at the MWNT film coated GCE was examined and
      it is found that this MWNT-modified GCE greatly enhances the oxidation peak
      current of tyrosine. Effects of some important factors, including pH, scan rate
      and amount of modifier, on the oxidation process of tyrosine were investigated.
      When the signal to noise ratio (SNR) is 3, the detection limit is 1 x 10(-7) M.
      The low relative standard deviations of the detection of tyrosine in human
      morning urine (3.3%) and white wine (5.2%) suggest a good reproducibility of the
      modified electrode.

PMID- 15503443
TI  - Functional micro- and nanoparticles based on poly[(N-acylimino)ethylene].

PMID- 15503444
TI  - In-situ crosslinking thermoreversible polymers for cell entrapment.

PMID- 15503445
TI  - pH-responsive hydrogels: swelling model.

PMID- 15503446
TI  - Smart elastin-like polymers.
AB  - Elastin-like polymers are a new family of proteinaceous polymers. In these
      polymers converge a wide set of interesting properties that difficultly can be
      found together in other polymers. They are extremely biocompatible and show an
      acute smart and self-assembling behaviour. The increasing in complexity of the
      molecular design renders polymers showing combination of functionalities and
      complex performance. This is specially true nowadays where, taking into account
      their peptide nature, these polymers can be produced as recombinant proteins in
      genetically modified (micro)organisms. The absolute control and absence of
      randomness in the primary structure makes possible the realization of
      multifunctional polymers that can combine physical, chemical and biological
      functions in a desired fashion. It can be said that the molecular design is
      mainly limited by imagination and not by technique. This chapter is intended to
      show the molecular parameters that explain the smart behaviour finally observed
      and how the increase in complexity of the molecular designs leads to a richer
      behaviour of the polymer, as a way to show the enormous potential of this family
      in the development of advanced materials and systems for biomedicine and
      nanotechnology for the next decades.

PMID- 15503447
TI  - Chitosan: a versatile biomaterial.

PMID- 15503449
TI  - Polyurethanes in biomedical applications.

PMID- 15503448
TI  - Bioapplication oriented polymers. Micro- and nanoparticles for drug delivery
      systems.

PMID- 15503450
TI  - Chemical durability of alumina and selected glasses in simulated body fluid:
      effect of composition and surface abrasion.

PMID- 15503451
TI  - Degradable phosphazene polymers and blends for biomedical applications.

PMID- 15503452
TI  - Molecularly imprinted polymers.

PMID- 15503453
TI  - Simulating hydroxyapatite binding of bone-seeking bisphosphonates.

PMID- 15503454
TI  - Biochips: focusing on surfaces and surface modification.

PMID- 15503455
TI  - Microarchitectural characterization of the aortic heart valve.

PMID- 15503456
TI  - Biodynamic modeling of human articulating joints.

PMID- 15503457
TI  - Novel bioabsorbable antibiotic releasing bone fracture fixation implants.

PMID- 15503458
TI  - Advances in analgesic drug design and delivery: a current survey.

PMID- 15503459
TI  - Drug delivery to brain by microparticulate systems.
AB  - The site specific delivery of chemotherapeutic agents allows maximum
      concentration of an agent at a desired body site. This area specific drug
      delivery decreases the unwanted systemic distribution and decreases toxicity of
      the administered drugs. Blood-Brain Barrier (BBB) is considered to be an obstacle
      in delivering large number of drugs to brain. The endothelial cells forming the
      tubular capillaries in the brain are cemented together by intercellular tight
      junctions. In this way, the BBB has an important role in providing a stable
      extracellular environment in the central nervous system. Lack of fenestrations,
      very few pinocytotic vesicles, and more mitochondria are other differences of the
      brain capillaries which play important role in transport of drugs to brain
      (Fig.1). The purpose of this paper is to summarise the methods for BBB
      permeability modifications and to focus on various examples in delivering drugs,
      especially neuroncology and neuroactive drugs, to brain by microparticulate
      systems.

PMID- 15503460
TI  - Bioadhesive drug carriers for postoperative chemotherapy in bladder cancer.
AB  - Transurethral resection (TUR) is the primary mode of therapy for both diagnosis
      and treatment of bladder cancer. Due to the recurrency of tumoral tissues after
      TUR further treatment is necessary which is usually in the form of intravesical
      chemotherapy or immunotherapy. But these therapies have some disadvantages such
      as disturbancy to patients, adjustment of the suitable dosage, loss of active
      agents without using. In this study, an alternative approach was proposed and
      pharmaco-therapeutic agent delivery systems which will supply the suitable dosage
      of the agent for a certain time period were designed to solve those problems. For
      this aim, Mitomycin-C loaded alginate and chitosan carriers were prepared to use
      as an alternative system in the post-operative chemotherapy in bladder cancer.
      The carriers were prepared in the form of cylindirical geometries to facilitate
      the insertion of the carrier in in vivo studies. The effects of some parameters
      (i.e., polymer MW, cross-linker concentration, Mitomycin-C/polymer ratio etc.)
      over the morphology, swelling behavior, bioadhesion and in-vitro drug release
      rate of the carriers were evaluated. The obtained results for chitosan and
      alginate carriers were concluded comparatively.

PMID- 15503461
TI  - Three-year follow-up of bioabsorbable PLLA cages for lumbar interbody fusion: in
      vitro and in vivo degradation.

PMID- 15503462
TI  - Metals foams for biomedical applications: processing and mechanical properties.

PMID- 15503463
TI  - Oral tissue engineering of complex tooth structures on biodegradable DLPLG/beta
      TCP scaffolds.

PMID- 15503464
TI  - Microparticulate release systems based on natural origin materials.

PMID- 15503465
TI  - Stem cells and tissue engineering.

PMID- 15503466
TI  - Cartilage tissue engineering.

PMID- 15503467
TI  - Towards dissecting the complexity of the AP-1 (activator protein 1) family.

PMID- 15503468
TI  - Health informatics.

PMID- 15503469
TI  - Ethics and animal use in biomedical research.

PMID- 15503470
TI  - A new concept of skeletal dysplasias.
AB  - The skeletal dysplasias form a large group of hereditary disorders characterized
      by abnormal growth and malformations of bone and cartilage. The clinical severity
      ranges from mildly affected short stature to lethal forms. Spranger classified
      approximately 200 different skeletal dysplasias in 1992, based on the clinical
      and radiographic features and the mode of genetic transmission. Etiopathogenesis
      of skeletal dysplasias is better documented now, with rapid accumulation of
      knowledge concerning defective genes and proteins causing this group of
      disorders. Mutations responsible for skeletal dysplasias may cause defects in the
      synthesis of structural proteins and in metabolic pathways, degradation of
      macromolecules, growth factors and receptors and transcription factors.
      Classifications by the International Working Group on Constitutional Diseases of
      Bone were based on the mutations in the same group gene taking into consideration
      the clinical and radiological findings (achondroplasia group, dysplasia with
      decreased bone density group and type II collagenopathies...). Clinical
      manifestations and radiological investigations are crucial for the differential
      diagnosis in skeletal dysplasias. However, prenatal diagnosis and postnatal
      definitive diagnosis are most often achieved by molecular analysis of the
      patient. Therefore, these groups of disorders require management by a
      multidisciplinary team of specialists, including pediatricians, genetic
      specialists, orthopedists and psychiatrists.

PMID- 15503471
TI  - Antioxidant enzymes in red blood cells and lymphocytes of ataxia-telangiectasia
      patients.
AB  - Toxic oxygen metabolites may contribute to the development of tissue damage, and
      play a role in the pathogenesis of malignancies, some acute and chronic pulmonary
      diseases, and in cell damage by radiomimetic agents, which can be seen in
      patients with ataxia-telangiectasia (A-T). Oxidative stress resulting from
      increased free radical production and/or defects in antioxidant defences is also
      involved in neurodegenerative disorders. Thus, oxidative stress could account for
      several aspects of the pleiotropic phenotype of A-T patients. The aim of this
      study was to determine the activities of the enzymes involved in cellular
      antioxidant metabolism in A-T patients to see if there is any defect which may
      result in constant oxidative stress. Superoxide dismutase (SOD) and catalase
      activities of erythrocytes, in contrast to lymphocytes, were found to be
      significantly higher in patients than in healthy controls. Our results may be
      another indication for the presence of constant oxidative stress in A-T patients
      as suggested previously.

PMID- 15503472
TI  - Defective anti-polysaccharide antibody response in patients with ataxia
      telangiectasia.
AB  - The immunodeficiency in ataxia-telangiectasia (A-T) patients involves both
      cellular and humoral immunity; however, the specific antibody response is not
      well defined. Frequent respiratory infections are a prominent feature in A-T.
      Streptococcus pneumoniae is a common pathogen responsible for these infections.
      Defective B cell membrane signaling has been reported in A-T cells. These
      observations prompted us to investigate the B cell response to six frequently
      encountered pneumococcal serotypes in A-T patients. We found defective IgG
      antibody production to all studied serotypes (3, 6B, 7F, 14, 19F, and 23F) in 22
      of 31 A-T patients (71%) who were immunized with a polyvalent pneumococcal
      vaccine. The impaired antibody responses did not correlate with either history of
      infection or serum immunoglobulin isotype levels. In addition, we did not observe
      any correlation between the pneumococcal antibody production and a specific
      mutation or level of intracellular ATM (ataxia-telangiectasia mutated) protein in
      lysates of lymphoblastoid cell lines from these patients. Our results suggest
      that the extent and severity of the recurrent sinopulmonary infections may depend
      not only on the immunological defects but also on other ATM-dependent
      physiological responses.

PMID- 15503473
TI  - The incidence and risk factors of neural tube defects in Izmir, Turkey: a nested
      case-control study.
AB  - The aim of this study was to determine the incidence of neural tube defects
      (NTDs) in Izmir, Turkey, and to evaluate risk factors that may be associated with
      NTD-affected pregnancies. A nested case-control study was carried out in all
      hospitals in Izmir. Controls were matched with cases on an individual basis
      according to the newborn's age and hospital in which they were born. There were
      56 newborns with NTD out of 36,331 deliveries in Izmir hospitals in 2000. The
      incidence of NTD was 1.5 per 1000 births. Forty-four cases and 88 controls were
      analyzed for risk factors. According to chi-square analysis, maternal education,
      paternal education, maternal nutritional status, maternal drug usage, and
      presence of maternal chronic diseases and acute infections during pregnancy were
      found significantly different between case and control groups.

PMID- 15503474
TI  - The prevalence of asthma and allergic diseases in children of school age in Adana
      in southern Turkey.
AB  - The aim of this study was to determine the prevalence of asthma and other
      allergic disorders as well as the factors affecting these disorders in school
      children in Adana. This cross-sectional population-based study using the
      International Study of Asthma and Allergies in Childhood (ISAAC) protocol was
      carried out on 3164 school-children aged between 6-18 years during March to June
      1997. There were 1521 (48.1%) boys and 1643 (51.9%) girls. The prevalence of
      asthma, allergic rhinitis and eczema in the 6-18 year-old children was found to
      be 12.6%, 13.6% and 8.3%, respectively. The prevalence of asthma was highest in 6
      10 year-old school-children (14.7%), and lowest (6.0%) in 15-18 year-old
      children. The prevalence of asthma diagnosed by a doctor was 5.0%. The cumulative
      and current prevalences of wheezing were found to be 19.0% and 13.5%,
      respectively. The cumulative prevalence of allergic disorders was found to be
      23.4%. The presence of domestic animals at home and dampness of the home were
      found to be important risk factors for asthma. Family histories of asthma,
      eczema, and diagnosis made by a doctor, and history of frequent sinusitis were
      found to be significantly higher in asthmatics. In conclusion, asthma is an
      important chronic disease of childhood in Adana in southern Turkey.

PMID- 15503475
TI  - Latex allergy and associated risk factors in a group of Turkish patients with
      spina bifida.
AB  - Allergic reactions to latex are common in patients with spina bifida. Its
      incidence varies between 28% and 67%. The aim of this study was to investigate
      the incidence of latex allergy and its risk factors in patients with spina bifida
      in Izmir, Turkey. Forty-six patients (24 male, mean age 10 years) were included
      in the study. A questionnaire was completed and skin prick tests with latex
      solution and cross-reacting foods were performed. Total IgE levels, specific IgE
      to common aeroallergens (Phadiotop), and latex specific IgE levels were measured.
      Patients with positive skin test reaction and/or who had specific IgE to latex
      without clinical symptoms were considered as sensitive to latex. The patients who
      also had clinical symptoms with latex exposure were diagnosed as allergic to
      latex. Latex sensitivity was found in 5/46 patients (10.8%). Only two patients
      had latex allergy (4.3%). Total IgE levels were higher (median 157 vs. 40 kU/L,
      p=0.012) and the duration of clean intermittent catheterization was longer
      insensitized patients when compared to non-sensitized patients (median 8 vs. 3
      years, p=0.015). Specific IgE to common aeroallergens and positive skin prick
      test to cross-reacting foods were more prevalent in sensitized than in non
      sensitized patients (p=0.02 and 0.015, respectively). The incidence of latex
      allergy in our group was lower than reported in the literature. This result may
      be due to the low number of surgical interventions. High levels of total IgE,
      positive Phadiotop, positive skin prick test to cross-reacting foods and the
      duration of clean intermittent catheterization are the risk factors for latex
      sensitivity in patients with spina bifida.

PMID- 15503476
TI  - Serum leptin levels of premature and full-term newborns in early infancy:
      metabolic catch-up of premature babies.
AB  - Leptin is secreted from the edipose tissue and has an important role in the
      regulation of energy metabolism. This study aimed to compare serum leptin levels
      of preterm and full-term infants during the first three months of their life and
      to define the roles of sex, weight, thickness of subcutaneous adipose tissue,
      gestational age and maternal leptin in the determination of serum leptin levels.
      Forty-four full-term and 32 preterm infants were included in the study. Weight,
      thickness of subcutaneous adipose tissue, serum glucose, cortisol, insulin and
      leptin levels were compared between preterm and full-term infants at 7th, 30th
      and 90th days. ELISA method was used in determining serum leptin levels. Weight,
      thickness of subcutaneous adipose tissue and serum leptin levels were
      significantly increased in full-term infants compared to preterm infants at days
      7 and 30. At 90th day weight and thickness of subcutaneous adipose tissue were
      significantly increased in full-term infants, but the difference in serum leptin
      levels did not reach statistical significance (p=0.56). Weight was the most
      important factor predicting serum leptin levels at the 7th day. On the other
      hand, the thickness of subcutaneous adipose tissue was the most important
      determinant at days 30 and 90. Maternal serum leptin level was a determinant of
      serum leptin level at day 7. Sex was a determinant of serum leptin level of the
      infant at days 7 and 30. The differences in weight gain, increase in thickness of
      subcutaneous adipose tissue and increase of serum leptin levels were not
      significant between groups. But the increase in serum leptin levels was
      correlated in both preterm and full-term infants with weight gain and increase in
      thickness of subcutaneous adipose tissue. At three months of age, in the catch-up
      growth period, preterm infants reach serum leptin levels near those of full-term
      infants. The thickness of subcutaneous adipose tissue has a role in the
      determination of serum leptin levels after 30 days of life.

PMID- 15503477
TI  - Alternative prognostic factors in pediatric embryonal rhabdomyosarcoma: Nm23
      expression, proliferative activity and angiogenesis.
AB  - Possible clinical relevance of Nm23 expression, angiogenesis and proliferative
      activity were evaluated as prognostic parameters in childhood embryonal
      rhabdomyosarcoma (RMS). Specimens of 25 RMS cases were studied for Nm23 antigen
      immunohistochemically. Vascular surface density (VSD) and number of vessels per
      stroma (NVES) calculated by stereologic methods on labeling sections with CD34
      antibody. For evaluation of proliferative activity of tumors, mitotic figures and
      Ki67 positive cells were investigated. All findings were searched statistically.
      Five patients were stage 1 (20%), two were stage 2 (8%), 15 were stage 3 (60%)
      and three were stage 4 (12%). The mean event free survival (EFS) was 20.8 and the
      mean overall survival (OS) was 25.9 months. Sixteen patients (64%) were alive and
      without disease. The percentage of Nm23 positivity was 52%. Log rank analysis
      showed Nm23 as a predictor for survival (p=0.0313). In Pearson correlation
      analysis, there was statistical significance between OS and presence of Nm23
      expression (p=0.044). VSD was also positively related with EFS (p=0.040). Despite
      the present parameters in use, there is a need for new prognostic markers,
      especially to predict the outcome of patients. These findings suggested that Nm23
      expression and VSD might be useful for follow-up in RMS.

PMID- 15503478
TI  - The relationships between candidemia and candidal colonization and virulence
      factors of the colonizing strains in preterm infants.
AB  - Premature infants are at high risk of developing candidal infections originating
      from their own normal flora or from the hospital environment. This study involves
      the surveillance cultures and blood cultures of candidemic preterm infants with
      low birth weights who have been analyzed for colonization period and status, and
      for virulence factors such as acid proteinase and phospholipase. Arbitrarily
      primed-polymerase chain reaction (AP-PCR) was applied to the blood culture
      isolates of the babies with candidemia and their last colonizing strains in order
      to determine whether the source of fungemia was the rectum. Of 65 colonized
      infants, 6.2% developed candidemia with identical strains originating from their
      rectum according to their PCR patterns. Our findings indicate that the properties
      of the colonizing yeasts such as increase in number--although not statistically
      significant because of the small sample size--and/or exhibition of strong
      hydrolytic enzyme activities through a long duration of colonization might
      contribute to the development of candidemia in preterms.

PMID- 15503479
TI  - Pediatric blood culture: time to positivity.
AB  - The aim of this study was to determine how long it takes blood culture to become
      positive using a blood culture system that can be monitored continuously in
      pediatric patients. Data were collected prospectively on 1,000 positive blood
      culture results from a tertiary pediatric university hospital from April 2000 to
      May 2002. The laboratory used the BACTEC 9120 fluorescent blood culture system.
      Patient's age ranged from less than a day to 20 years of age (mean 3 years). Five
      hundred and four cultures (50.4%) out of 1,000 yielded coagulase negative
      staphylococcus (CNS), 81 (8.1%) S. aureus, 53 (5.3%). Pseudomonas and 50 (5.0%)
      Klebsiella species. Of the 504 coagulase negative staphylococcal blood culture
      isolates, 314 (62.3% of CNS) were regarded as skin contaminants. Of the 1,000
      cultures, 9.6% were reported as positive in the first day, 27.8% in the second
      day, 54.7% in the third day, 77.0% in the fourth and 89.4% in the fifth day.
      There was no association between previous antibiotic usage and the period
      required for isolate recovery. The clinician can expect to get results of
      positive blood cultures with susceptibility data, at a rate of 77.1% by day four
      and almost 90% by day five of sampling in the bacteriemic patient. Blood cultures
      yielding coagulase negative staphylococci in the first three days almost always
      show bacteremia with those microorganisms.

PMID- 15503481
TI  - Back to the basics: hemorrhage after vaccination: a case report.
AB  - A 50-day-old girl with swelling and ecchymosis of right hand dorsum after DTP
      vaccination on ipsilateral deltoid area was referred to the pediatric infectious
      disease outpatient unit with a presumed diagnosis of gangrenous cellulites.
      Physical examination and laboratory evaluation revealed intramuscular bleeding as
      a result of vitamin K deficiency. We would like to emphasize the importance of
      both vitamin K prophylaxis in the newborn to prevent hemorrhagic disease of the
      newborn and of the education of persons administering vaccines about this very
      basic aspect of pediatrics for early recognition.

PMID- 15503480
TI  - Acute arterial thrombotic purpura complicating varicella and the role of
      hyperbaric oxygen as an adjunctive therapy.
AB  - Chickenpox is a common infectious disease of the pediatric age group with rare
      complications such as hemorrhagic varicella and arterial thrombotic purpura.
      Medical support is the mainstay of treatment in such cases but for the rescue of
      necrotic tissues, hyperbaric oxygen (HBO) therapy should be applied in addition
      to anticoagulant intervention. We report an infant with acute arterial thrombotic
      purpura which developed after varicella eruption and who made full recovery with
      the help of HBO as an adjunctive treatment modality. Fresh frozen plasma and low
      molecular weight heparin were given for prolonged prothrombin time and
      thromboemboli on the 2nd-4th digits of his right foot. Protein C, protein S and
      factor V levels were found to be normal in our patient. Necrotic lesions on the
      toes regressed with repeated HBO treatment and amputation was not needed.

PMID- 15503482
TI  - Effectiveness of somatostatin in the conservative management of chylothorax.
AB  - Chylothorax is a rare but potentially serious and well recognized cause of
      pleural effusion. Chylothorax commonly occurs following general thoracic and
      cardiac procedures. Additionally it sometimes develops secondary to non-surgical
      trauma, i.e. weight lifting. Here we report two additional cases with
      chylothorax. Somatostatin was added to conservative treatment protocol to
      increase effectiveness of therapy in both cases. Although the first case required
      surgical intervention, we avoided any surgical procedure in the second patient
      with conservative management combined with somatostatin.

PMID- 15503483
TI  - Thrombocytopenic purpura as only manifestation of brucellosis in a child.
AB  - Thrombocytopenic purpura associated with brucellosis has been rarely reported in
      the world literature. Thrombocytopenic purpura is generally part of the array of
      manifestations of brucellosis such as fever, arthritis, malaise and
      hepatosplenomegaly. We describe a nine-year-old girl who presented with
      thrombocytopenic purpura as the sole manifestation of brucellosis, which resolved
      with anti-Brucella chemotherapy. Her physical examination was remarkable for
      hepatomegaly of 3 cm and splenomegaly of 2 cm palpable below the costal margin.
      Initial laboratory investigations revealed isolated thrombocytopenia with
      platelet count of 11,300/mm3 and positive serology for Brucella. Thrombocytopenia
      resolved promptly with proper antibiotics on 7th day of treatment. Brucellosis
      should be included in the differential diagnosis of thrombocytopenic purpura in
      Brucella-endemic areas.

PMID- 15503484
TI  - Endobronchial stenting in a two-month-old infant with bronchial compression
      secondary to tetralogy of Fallot and absent pulmonary valve.
AB  - Bronchial compression due to pulmonary artery dilation is an important problem in
      infants with congenital heart disease, and can complicate the postoperative
      course. In recent years, airway stenting has become a popular treatment for these
      cases. We achieved success with endobronchial stenting in a two-month-old infant
      with bronchial compression caused by a dilated pulmonary artery.

PMID- 15503485
TI  - A case of patent ductus venosus with pulmonary arterio-venous fistula as a rare
      and unique clinical entity.
AB  - A 13-year-old boy presenting with digital and lip cyanosis, easy fatigability,
      and weight gain was diagnosed to have an intrapulmonary arterio-venous fistula.
      During his routine follow-up examinations, there was fullness on right upper
      quadrant of his abdomen. Abdominal ultrasonography (USG) showed a mass in portal
      hilus. We planned abdominal computed (CT) to gain tomography detailed information
      about the mass. Surprisingly abdominal CT and the color-Doppler sonography showed
      that the structure mimicking a mass was patent ductus venosus (PDV). We report
      PDV with intrapulmonary arterio-venous fistula as a unique and rare clinical
      entity. In addition, we underline the misdiagnosis of portal mass instead of
      patent ductus venosus. If there is a portal mass in USG or CT, color-Doppler
      sonography or, if needed, other diagnostic methods should be used to exclude PDV.

PMID- 15503486
TI  - Perigraft seroma complicating the modified Blalock-Taussig shunts: two
      consecutive instances with review of literature.
AB  - Systemic-to-pulmonary artery shunts using polytetrafluoroethylene (PTFE)
      (modified Blalock-Taussig shunt) are being used successfully in palliation of
      cyanotic congenital heart diseases. Graft thrombosis is by far the most common
      complication of the procedure. Persistant serum leakage through PTFE graft
      causing perigraft seroma is a rare but devastating complication resulting in
      increased duration of tube drainage or reinsertion of chest tubes, prolonged
      hospital stay, and multiple operations. Two consecutive modified Blalock-Taussig
      shunts complicated by perigraft seroma formation are presented here with review
      of the literature.

PMID- 15503487
TI  - Pyogenic liver abscesses in a child spreading to pulmonary and subcutaneous
      tissues: case report.
AB  - Pyogenic liver abscess is a rare and life-threatening disease in children. Our
      case is noteworthy because of the rapid advancement of liver abscesses without
      any other systemic disorder. A 16-year-old girl was admitted to the hospital with
      fatigue, pallor, weight loss and high fever. In physical examination a
      fluctuating mass was observed under the scapular area and hepatosplenomegaly was
      found. In computed tomography, three septated cystic lesions which looked like
      abscesses were demonstrated in the liver. The abscess was drained through
      percutaneous route. Right pleural empyema with clinical features of adult
      respiratory distress syndrome appeared after the first day of treatment.
      Bacteroides sp. was isolated from pus. On the twentieth day of the therapy,
      control abdominal computed tomography revealed two new abscesses in the liver.
      They were drained and the antibiotic therapy was continued with ticarcillin
      clavulanate, fluconazole and levofloxacin. By the end of the first week of the
      therapy, the fever of the patient had abated. This therapy was continued for four
      weeks; 15 days after the end of the therapy there was prominent healing of the
      liver lesions with only one necrotic remnant 2 cm in diameter on abdominal
      computed tomography.

PMID- 15503488
TI  - Prenatal diagnosis of Meckel-Gruber syndrome and Dandy-Walker malformation in
      four consecutive affected siblings, with the fourth one being diagnosed
      prenatally at 22 weeks of gestation.
AB  - We report a 23-week-old male fetus affected by Meckel-Gruber syndrome. Posterior
      encephalocele, post-axial polydactyly, and Dandy-Walker malformation were
      observed on ultrasonographic (USG) examination at 22 weeks' gestation, and lobar
      holoprosencephaly was demonstrated on postmortem magnetic resonance imaging (MRI)
      prior to autopsy. After the termination of the pregnancy, polycystic dysplastic
      kidneys were also noted at postmortem investigation. The proband was the product
      of the fourth pregnancy of a consanguineous family in which all three siblings
      were also similarly affected. Interestingly, both the two-year-old affected
      sister and 23-week-old male fetus had Dandy-Walker complex.

PMID- 15503489
TI  - Successful treatment of enterocutaneous fistula in a premature newborn by using
      octreotide.
AB  - A premature newborn with an enterocutaneous fistula after repair of duodenal
      perforation is reported to emphasize the therapeutic effect of octreotide in
      persistent fistula even in a very small infant. Our report showed that use of
      octreotide was safe even in premature infants with intestinal fistula. Close
      monitorization of biochemical and blood parameters is needed in patients treated
      with octreotide.

PMID- 15503490
TI  - Mega dose methylprednisolone (MDMP) treatment.

PMID- 15503491
TI  - An improved LDA approach.
AB  - Linear discrimination analysis (LDA) technique is an important and well-developed
      area of image recognition and to date many linear discrimination methods have
      been put forward. Despite these efforts, there persist in LDA at least three
      areas of weakness. The first weakness is that not all the discrimination vectors
      that are obtained are useful in pattern classification. Second, it remains
      computationally expensive to make the discrimination vectors completely satisfy
      statistical uncorrelation. The third weakness is that it is necessary to select
      the appropriate principal components. In this paper, we propose to improve
      discrimination technique in these three areas and to that end present an improved
      LDA (ILDA) approach which synthesizes these improvements. Experimental results on
      different image databases demonstrate that our improvements on LDA are efficient,
      and that ILDA outperforms other state-of-the-art linear discrimination methods.

PMID- 15503492
TI  - OWA aggregation over a continuous interval argument with applications to decision
      making.
AB  - We briefly describe the ordered weighted average (OWA) operator. We discuss its
      role in decision making under uncertainty. We provide an extension of the OWA
      operator to the case in which our argument is a continuous valued interval rather
      than a finite set of values. We look at some examples of this type of
      aggregation. We show how it can be used in some tasks that arise in decision
      making. We consider the extension of the continuous interval argument OWA
      operator to the more general case in which the argument values have importance
      weights. We use this to introduce the idea of an attitudinal-based expected value
      associated with a continuous random variable.

PMID- 15503493
TI  - A methodology for extracting objective color from images.
AB  - We present a methodology for correcting color images taken in practical indoor
      environments, such as laboratories, factories, and studios, that explicitly
      models illuminant location, surface reflectance and geometry, and camera
      responsivity. We explicitly model surfaces by taking our color images with
      corresponding registered three-dimensional (3-D) range images, which provide
      surface orientation and location information for every point in the scene. We
      automatically detect regions where color correction should not be applied, such
      as specularities, coarse texture regions, and jump edges. This correction results
      in objective color measures of the imaged surfaces. This kind of integrated,
      comprehensive system of color correction has not existed until now. i.e., it is
      the first of its kind in computer vision. We demonstrate results of applying this
      methodology to real images for applications in photorealistic rerendering, skin
      lesion detection, burn scar color measurement, and general color image
      enhancement. We also have tested the method under different lighting
      configurations and with three different range scanners.

PMID- 15503494
TI  - Handling interaction in fuzzy production rule reasoning.
AB  - When fuzzy production rules are used to approximate reasoning, interaction exists
      among rules that have the same consequent. Due to this interaction, the weighted
      average model frequently used in approximate reasoning does not work well in many
      real-world problems. In order to model and handle this interaction, this paper
      proposes to use a nonadditive nonnegative set function to replace the weights
      assigned to rules having the same consequent, and to draw the reasoning
      conclusion based on an integral with respect to the nonadditive nonnegative set
      function, rather than on the weighted average model. Handling interaction in
      fuzzy production rule reasoning in this way can lead to a good understanding of
      the rules base and an improvement of reasoning accuracy. This paper also
      investigates how to determine from data the nonadditive set function that cannot
      be specified by a domain expert.

PMID- 15503495
TI  - A subsumptive, hierarchical, and distributed vision-based architecture for smart
      robotics.
AB  - We present a distributed vision-based architecture for smart robotics that is
      composed of multiple control loops, each with a specialized level of competence.
      Our architecture is subsumptive and hierarchical, in the sense that each control
      loop can add to the competence level of the loops below, and in the sense that
      the loops can present a coarse-to-fine gradation with respect to vision sensing.
      At the coarsest level, the processing of sensory information enables a robot to
      become aware of the approximate location of an object in its field of view. On
      the other hand, at the finest end, the processing of stereo information enables a
      robot to determine more precisely the position and orientation of an object in
      the coordinate frame of the robot. The processing in each module of the control
      loops is completely independent and it can be performed at its own rate. A
      control Arbitrator ranks the results of each loop according to certain confidence
      indices, which are derived solely from the sensory information. This architecture
      has clear advantages regarding overall performance of the system, which is not
      affected by the "slowest link," and regarding fault tolerance, since faults in
      one module does not affect the other modules. At this time we are able to
      demonstrate the utility of the architecture for stereoscopic visual servoing. The
      architecture has also been applied to mobile robot navigation and can easily be
      extended to tasks such as "assembly-on-the-fly."

PMID- 15503496
TI  - Efficient generation of discontinuity-preserving adaptive triangulations from
      range images.
AB  - This paper presents an efficient technique for generating adaptive triangular
      meshes from range images. The algorithm consists of two stages. First, a user
      defined number of points is adaptively sampled from the given range image. Those
      points are chosen by taking into account the surface shapes represented in the
      range image in such a way that points tend to group in areas of high curvature
      and to disperse in low-variation regions. This selection process is done through
      a noniterative, inherently parallel algorithm in order to gain efficiency. Once
      the image has been subsampled, the second stage applies a two and one half
      dimensional Delaunay triangulation to obtain an initial triangular mesh. To favor
      the preservation of surface and orientation discontinuities (jump and crease
      edges) present in the original range image, the aforementioned triangular mesh is
      iteratively modified by applying an efficient edge flipping technique. Results
      with real range images show accurate triangular approximations of the given range
      images with low processing times.

PMID- 15503497
TI  - Multirobot systems: a classification focused on coordination.
AB  - Multirobot systems (MRS) are, nowadays, an important research area within
      robotics and artificial intelligence and a growing number of systems have
      recently been presented in the literature. Since application domains and tasks
      that are faced by MRS are of increasing complexity, the ability of the robots to
      cooperate can be regarded as a fundamental feature. In this paper, we present a
      survey of the recent work in the area by specifically examining the forms of
      cooperation and coordination realized in the MRS. In particular, we propose a new
      taxonomy for classification of the approaches to coordination in MRS and we
      describe some systems, which we consider representative in our taxonomy. We
      finally discuss the outcomes of our analysis and try to highlight future trends
      of the research on MRS.

PMID- 15503498
TI  - Intelligent decision making in disassembly process based on fuzzy reasoning petri
      nets.
AB  - Practical disassembly process planning is extremely important for efficient
      material recycling and components reuse. The research work for the process
      planning in literature focuses on the generation of optimal sequences based on
      the predictive information of products. The used products, unfortunately, exhibit
      high uncertainty since products may experience very different conditions during
      their use stage. The indeterminate characteristics associated to used products
      often makes the predetermined plan unrealistic. Their disassembly process has to
      be decided dynamically adaptive to the products' specific status. To be able to
      deal with uncertainty in a dynamic decision making process, this paper presents a
      fuzzy reasoning Petri net (FRPN) model to represent related decision making rules
      in disassembly process. Using the proposed fuzzy reasoning algorithm based on the
      FRPN model, the multicriterion disassembly rules can be considered in the
      parallel way to make the decision automatically and quickly. Instead of producing
      the disassembly sequences before disassembling a whole product, the proposed
      method makes intelligent decisions based on dynamically updated status of
      components in the product at each disassembly step. Therefore, it is adaptive to
      the changes that arise during the process. Finally, an example is used to
      illustrate the application of the proposed methodology.

PMID- 15503499
TI  - Stochastic clustering for organizing distributed information sources.
AB  - The number of information sources and the volumes of data in these information
      sources have greatly increased, which may be attributed to the ever-increasing
      complexity of real-world applications. The enormous amount of information
      available in the information sources in a distributed information-providing
      environment has created a need to provide users with tools to effectively and
      efficiently navigate and retrieve information. Queries in such an environment
      often access information from multiple information sources. This may be
      attributed to navigational characteristics. Clusters provide a structure for
      organizing the large number of information sources for efficient browsing,
      searching, and retrieval. This paper presents a stochastically-based clustering
      mechanism, called the Markov model mediator (MMM), to group the information
      sources into a set of useful clusters. Each information source cluster groups
      those information sources that show similarities in their data access behavior.
      Information sources within the same cluster are expected to be able to provide
      most of the required information among themselves for user queries that are
      closely related with respect to a particular application. This can significantly
      improve system response time, query performance, and result in an overall
      improvement in decision support. Empirical studies on real databases are
      performed and the results demonstrate that our proposed mechanism leads to a
      better set of clusters in comparison with other clustering methods. This serves
      to illustrate the effectiveness of our proposed MMM mechanism.

PMID- 15503500
TI  - Robust adaptive neural network control of uncertain nonholonomic systems with
      strong nonlinear drifts.
AB  - In this paper, robust adaptive neural network (NN) control is presented to solve
      the control problem of nonholonomic systems in chained form with unknown virtual
      control coefficients and strong drift nonlinearities. The robust adaptive NN
      control laws are developed using state scaling and backstepping. Uniform ultimate
      boundedness of all the signals in the closed-loop are guaranteed, and the system
      states are proven to converge to a small neighborhood of zero. The control
      performance of the closed-loop system is guaranteed by appropriately choosing the
      design parameters. The proposed adaptive NN control is free of control
      singularity problem. An adaptive control based switching strategy is used to
      overcome the uncontrollability problem associated with x0 (t0) = 0. The
      simulation results demonstrate the effectiveness of the proposed controllers.

PMID- 15503501
TI  - Constructing a user-friendly GA-based fuzzy system directly from numerical data.
AB  - This paper proposes a novel genetic algorithms (GA)-based algorithm to construct
      a user-friendly fuzzy system for approximating an unknown system with a
      satisfactory degree of accuracy. In the algorithm, the adequate number of fuzzy
      rules, the adequate number of membership functions of each input variable, and
      the parameters of membership functions will be determined automatically; in
      addition, the dummy input variables will be detected and discarded. Finally,
      several typical examples are illustrated to show the effectiveness of the
      algorithm.

PMID- 15503502
TI  - Finding relevant sequences in time series containing crisp, interval, and fuzzy
      interval data.
AB  - Finding similar sequences in time series has received much attention and is a
      widely studied topic. Most existing approaches in the time series area focus on
      the efficiency of algorithms but seldom provide a means to handle imprecise data.
      In this paper, a more general approach is proposed to measure the distance of
      time sequences containing crisp values, intervals, and fuzzy intervals as well.
      The concept of distance measurement and its associated dynamic-programming-based
      algorithms are described. In addition to finding the sequences with similar
      evolving trends, a means of finding the sequences with opposite evolving
      tendencies is also proposed, which is usually omitted in current related research
      but could be of great interest to many users.

PMID- 15503503
TI  - Cumulative distribution functions from Dempster-Shafer belief structures.
AB  - We discuss the Dempster-Shafer belief structure. We introduce the idea of a
      cumulative distribution induced by a Dempster-Shafer belief structure. We call
      these belief-cumulative distribution (B-CDs) functions. We study the properties
      of these distribution functions and show that they are interval functions. We
      investigate the possibility of using these distribution functions as a tool for
      knowledge representation.

PMID- 15503505
TI  - Intelligent motion control for linear piezoelectric ceramic motor drive.
AB  - Since the dynamic characteristics of a linear piezoelectric ceramic motor (LPCM)
      are highly nonlinear and time varying, it is difficult to design a suitable motor
      drive and position controller that realizes accurate position control at all
      time. This study investigates a double-inductance double-capacitance (LLCC)
      resonant driving circuit and a sliding-mode fuzzy-neural-network control (SMFNNC)
      system for the motion control of an LPCM. First, the motor structure and LLCC
      driving circuit of an LPCM are introduced. The LLCC resonant inverter is designed
      to operate at an optimal switching frequency such that the output voltage will
      not be influenced by the variation of quality factor. Moreover, a SMFNNC system
      is designed to achieve favorable tracking performance without precise dynamic
      models being controlled. All adaptive learning algorithms in the SMFNNC system
      are derived in the sense of Lyapunov stability analysis, so that system-tracking
      stability can be guaranteed in the closed-loop system. The effectiveness of the
      proposed driving circuit and control system is verified by experimental results.

PMID- 15503504
TI  - Multiobjective GAs, quantitative indices, and pattern classification.
AB  - The concept of multiobjective optimization (MOO) has been integrated with
      variable length chromosomes for the development of a nonparametric genetic
      classifier which can overcome the problems, like overfitting/overlearning and
      ignoring smaller classes, as faced by single objective classifiers. The
      classifier can efficiently approximate any kind of linear and/or nonlinear class
      boundaries of a data set using an appropriate number of hyperplanes. While
      designing the classifier the aim is to simultaneously minimize the number of
      misclassified training points and the number of hyperplanes, and to maximize the
      product of class wise recognition scores. The concepts of validation set (in
      addition to training and test sets) and validation functional are introduced in
      the multiobjective classifier for selecting a solution from a set of nondominated
      solutions provided by the MOO algorithm. This genetic classifier incorporates
      elitism and some domain specific constraints in the search process, and is called
      the CEMOGA-Classifier (constrained elitist multiobjective genetic algorithm based
      classifier). Two new quantitative indices, namely, the purity and minimal
      spacing, are developed for evaluating the performance of different MOO
      techniques. These are used, along with classification accuracy, required number
      of hyperplanes and the computation time, to compare the CEMOGA-Classifier with
      other related ones.

PMID- 15503506
TI  - Online learning of virtual impedance parameters in non-contact impedance control
      using neural networks.
AB  - Impedance control is one of the most effective methods for controlling the
      interaction between a manipulator and a task environment. In conventional
      impedance control methods, however, the manipulator cannot be controlled until
      the end-effector contacts task environments. A noncontact impedance control
      method has been proposed to resolve such a problem. This method on only can
      regulate the end-point impedance, but also the virtual impedance that works
      between the manipulator and the environment by using visual information. This
      paper proposes a learning method using neural networks to regulate the virtual
      impedance parameters according to a given task. The validity of the proposed
      method was verified through computer simulations and experiments with a
      multijoint robotic manipulator.

PMID- 15503507
TI  - A noisy chaotic neural network for solving combinatorial optimization problems:
      stochastic chaotic simulated annealing.
AB  - Recently Chen and Aihara have demonstrated both experimentally and mathematically
      that their chaotic simulated annealing (CSA) has better search ability for
      solving combinatorial optimization problems compared to both the Hopfield-Tank
      approach and stochastic simulated annealing (SSA). However, CSA may not find a
      globally optimal solution no matter how slowly annealing is carried out, because
      the chaotic dynamics are completely deterministic. In contrast, SSA tends to
      settle down to a global optimum if the temperature is reduced sufficiently
      slowly. Here we combine the best features of both SSA and CSA, thereby proposing
      a new approach for solving optimization problems, i.e., stochastic chaotic
      simulated annealing, by using a noisy chaotic neural network. We show the
      effectiveness of this new approach with two difficult combinatorial optimization
      problems, i.e., a traveling salesman problem and a channel assignment problem for
      cellular mobile communications.

PMID- 15503508
TI  - A unified quadratic-programming-based dynamical system approach to joint torque
      optimization of physically constrained redundant manipulators.
AB  - In this paper, for joint torque optimization of redundant manipulators subject to
      physical constraints, we show that velocity-level and acceleration-level
      redundancy-resolution schemes both can be formulated as a quadratic programming
      (QP) problem subject to equality and inequality/bound constraints. To solve this
      QP problem online, a primal-dual dynamical system solver is further presented
      based on linear variational inequalities. Compared to previous researches, the
      presented QP-solver has simple piecewise-linear dynamics, does not entail real
      time matrix inversion, and could also provide joint-acceleration information for
      manipulator torque control in the velocity-level redundancy-resolution schemes.
      The proposed QP-based dynamical system approach is simulated based on the PUMA560
      robot arm with efficiency and effectiveness demonstrated.

PMID- 15503509
TI  - Gain-phase margin analysis of dynamic fuzzy control systems.
AB  - In this paper, we apply some effective methods, including the gain-phase margin
      tester, describing function and parameter plane, to predict the limit cycles of
      dynamic fuzzy control systems with adjustable parameters. Both continuous-time
      and sampled-data fuzzy control systems are considered. In general, fuzzy control
      systems are nonlinear. By use of the classical method of describing functions,
      the dynamic fuzzy controller may be linearized first. According to the stability
      equations and parameter plane methods, the stability of the equivalent linearized
      system with adjustable parameters is then analyzed. In addition, a simple
      approach is also proposed to determine the gain margin and phase margin which
      limit cycles can occur for robustness. Two examples of continuous-time fuzzy
      control systems with and without nonlinearity are presented to demonstrate the
      design procedure. Finally, this approach is also extended to a sampled-data fuzzy
      control system.

PMID- 15503510
TI  - A new Q-learning algorithm based on the metropolis criterion.
AB  - The balance between exploration and exploitation is one of the key problems of
      action selection in Q-learning. Pure exploitation causes the agent to reach the
      locally optimal policies quickly, whereas excessive exploration degrades the
      performance of the Q-learning algorithm even if it may accelerate the learning
      process and allow avoiding the locally optimal policies. In this paper, finding
      the optimum policy in Q-learning is described as search for the optimum solution
      in combinatorial optimization. The Metropolis criterion of simulated annealing
      algorithm is introduced in order to balance exploration and exploitation of Q
      learning, and the modified Q-learning algorithm based on this criterion, SA-Q
      learning, is presented. Experiments show that SA-Q-learning converges more
      quickly than Q-learning or Boltzmann exploration, and that the search does not
      suffer of performance degradation due to excessive exploration.

PMID- 15503511
TI  - Prediction and identification using wavelet-based recurrent fuzzy neural
      networks.
AB  - This paper presents a wavelet-based recurrent fuzzy neural network (WRFNN) for
      prediction and identification of nonlinear dynamic systems. The proposed WRFNN
      model combines the traditional Takagi-Sugeno-Kang (TSK) fuzzy model and the
      wavelet neural networks (WNN). This paper adopts the nonorthogonal and compactly
      supported functions as wavelet neural network bases. Temporal relations embedded
      in the network are caused by adding some feedback connections representing the
      memory units into the second layer of the feedforward wavelet-based fuzzy neural
      networks (WFNN). An online learning algorithm, which consists of structure
      learning and parameter learning, is also presented. The structure learning
      depends on the degree measure to obtain the number of fuzzy rules and wavelet
      functions. Meanwhile, the parameter learning is based on the gradient descent
      method for adjusting the shape of the membership function and the connection
      weights of WNN. Finally, computer simulations have demonstrated that the proposed
      WRFNN model requires fewer adjustable parameters and obtains a smaller rms error
      than other methods.

PMID- 15503512
TI  - A relaxed stability criterion for T-S fuzzy discrete systems.
AB  - Stability conditions for Tanaka-Sugeno (T-S) fuzzy discrete systems based on a
      single quadratic Lyapunov function or a weighting dependent Lyapunov function
      have been mentioned in lots of literature. The existence of a common matrix P is
      required in the former, and r (rules' number) positive matrices satisfying r2
      Lyapunov inequalities are necessary in the latter. In this paper, the weighting
      dependent Lyapunov function is used again. Moreover according to the idea of the
      firing rule group and the distance estimation between two successive states of
      the system, the relaxed stability criterion of T-S fuzzy discrete system is
      proposed.

PMID- 15503513
TI  - Diagnosis of complex systems: bridging the methodologies of the FDI and DX
      communities.

PMID- 15503514
TI  - Conflicts versus analytical redundancy relations: a comparative analysis of the
      model based diagnosis approach from the artificial intelligence and automatic
      control perspectives.
AB  - Two distinct and parallel research communities have been working along the lines
      of the model-based diagnosis approach: the fault detection and isolation (FDI)
      community and the diagnostic (DX) community that have evolved in the fields of
      automatic control and artificial intelligence, respectively. This paper clarifies
      and links the concepts and assumptions that underlie the FDI analytical
      redundancy approach and the DX consistency-based logical approach. A formal
      framework is proposed in order to compare the two approaches and the theoretical
      proof of their equivalence together with the necessary and sufficient conditions
      is provided.

PMID- 15503515
TI  - Hybrid estimation of complex systems.
AB  - Modern automated systems evolve both continuously and discretely, and hence
      require estimation techniques that go well beyond the capability of a typical
      Kalman Filter. Multiple model (MM) estimation schemes track these system
      evolutions by applying a bank of filters, one for each discrete system mode.
      Modern systems, however, are often composed of many interconnected components
      that exhibit rich behaviors, due to complex, system-wide interactions. Modeling
      these systems leads to complex stochastic hybrid models that capture the large
      number of operational and failure modes. This large number of modes makes a
      typical MM estimation approach infeasible for online estimation. This paper
      analyzes the shortcomings of MM estimation, and then introduces an alternative
      hybrid estimation scheme that can efficiently estimate complex systems with large
      number of modes. It utilizes search techniques from the toolkit of model-based
      reasoning in order to focus the estimation on the set of most likely modes,
      without missing symptoms that might be hidden amongst the system noise. In
      addition, we present a novel approach to hybrid estimation in the presence of
      unknown behavioral modes. This leads to an overall hybrid estimation scheme for
      complex systems that robustly copes with unforeseen situations in a degraded, but
      fail-safe manner.

PMID- 15503516
TI  - Possible conflicts: a compilation technique for consistency-based diagnosis.
AB  - Consistency-based diagnosis is one of the most widely used approaches to model
      based diagnosis within the artificial intelligence community. It is usually
      carried out through an iterative cycle of behavior prediction, conflict
      detection, candidate generation, and candidate refinement. In that process
      conflict detection has proven to be a nontrivial step from the theoretical point
      of view. For this reason, many approaches to consistency-based diagnosis have
      relied upon some kind of dependency-recording. These techniques have had
      different problems, specially when they were applied to diagnose dynamic systems.
      Recently, offline dependency compilation has established itself as a suitable
      alternative approach to online dependency-recording. In this paper we propose the
      possible conflict concept as a compilation technique for consistency-based
      diagnosis. Each possible conflict represents a subsystem within system
      description containing minimal analytical redundancy and being capable to become
      a conflict. Moreover, the whole set of possible conflicts can be computed offline
      with no model evaluation. Once we have formalized the possible conflict concept,
      we explain how possible conflicts can be used in the consistency-based diagnosis
      framework, and how this concept can be easily extended to diagnose dynamic
      systems. Finally, we analyze its relation to conflicts in the general diagnosis
      engine (GDE) framework and compare possible conflicts with other compilation
      techniques, especially with analytical redundancy relations (ARRs) obtained
      through structural analysis. Based on results from these comparisons we provide
      additional insights in the work carried out within the BRIDGE community to
      provide a common framework for model-based diagnosis for both artificial
      intelligence and control engineering approaches.

PMID- 15503517
TI  - Combining FDI and AI approaches within causal-model-based diagnosis.
AB  - This paper presents a model-based diagnostic method designed in the context of
      process supervision. It has been inspired by both artificial intelligence and
      control theory. AI contributes tools for qualitative modeling, including causal
      modeling, whose aim is to split a complex process into elementary submodels.
      Control theory, within the framework of fault detection and isolation (FDI),
      provides numerical models for generating and testing residuals, and for taking
      into account inaccuracies in the model, unknown disturbances and noise.
      Consistency-based reasoning provides a logical foundation for diagnostic
      reasoning and clarifies fundamental assumptions, such as single fault and
      exoneration. The diagnostic method presented in the paper benefits from the
      advantages of all these approaches. Causal modeling enables the method to focus
      on sufficient relations for fault isolation, which avoids combinatorial
      explosion. Moreover, it allows the model to be modified easily without changing
      any aspect of the diagnostic algorithm. The numerical submodels that are used to
      detect inconsistency benefit from the precise quantitative analysis of the FDI
      approach. The FDI models are studied in order to link this method with DX
      component-oriented reasoning. The recursive on-line use of this algorithm is
      explained and the concept of local exoneration is introduced.

PMID- 15503518
TI  - A bridged diagnostic method for the monitoring of polymorphic discrete-event
      systems.
AB  - Diagnosis of discrete-event systems (DESs) is a challenging problem that has been
      tackled both by automatic control and artificial intelligence communities. The
      relevant approaches share similarities, including modeling by automata,
      compositional modeling, and model-based reasoning. This paper aims to bridge two
      complementary approaches from these communities, namely, the diagnoser approach
      and the active system approach, respectively. The more significant shortcomings
      of such approaches are, on the one side, the need for the generation of the
      global system model and, on the other, the lack of monitoring capabilities. The
      former makes the application of the diagnoser approach prohibitive in real
      contexts, where the system model is too large to be generated, even offline. The
      latter requires the completion of the system observation before starting the
      diagnostic task, thereby, making the monitoring of the system. impossible. The
      bridged diagnostic method subsumes, to a large extent on the peculiarities of the
      two approaches and is capable of coping with an extended class of DESs that
      integrate both synchronous and asynchronous behavior. The bridge is built by
      extending the active system approach by means of several enhanced techniques,
      which eventually, allow the efficient monitoring of polymorphic DESs. Upon the
      occurrence of each system message, two pieces of diagnostic information are
      generated, namely, the snapshot and historic diagnostic sets. While the former
      accounts for the faults pertinent to the newly generated message only, the latter
      is based on the whole sequence of messages yielded by the system during
      operation.

PMID- 15503519
TI  - Involuntary treatment of the mentally ill: autonomy is asking the wrong question.

PMID- 15503520
TI  - History of immediate load in implant dentistry. Interview.

PMID- 15503521
TI  - Exposure of lima bean leaves to volatiles from herbivore-induced conspecific
      plants results in emission of carnivore attractants: active or passive process?
AB  - There is increasing evidence that volatiles emitted by herbivore-damaged plants
      can cause responses in downwind undamaged neighboring plants, such as the
      attraction of carnivorous enemies of herbivores. One of the open questions is
      whether this involves an active (production of volatiles) or passive (adsorption
      of volatiles) response of the uninfested downwind plant. This issue is addressed
      in the present study. Uninfested lima bean leaves that were exposed to volatiles
      from conspecific leaves infested with the spider mite Tetranychus urticae,
      emitted very similar blends of volatiles to those emitted from infested leaves
      themselves. Treating leaves with a protein-synthesis inhibitor prior to infesting
      them with spider mites completely suppressed the production of herbivore-induced
      volatiles in the infested leaves. Conversely, inhibitor treatment to uninfested
      leaves prior to exposure to volatiles from infested leaves did not affect the
      emission of volatiles from the exposed, uninfested leaves. This evidence supports
      the hypothesis that response of the exposed downwind plant is passive. T. urticae
      infested leaves that had been previously exposed to volatiles from infested
      leaves emitted more herbivore-induced volatiles than T. urticae-infested leaves
      previously exposed to volatiles from uninfested leaves. The former leaves were
      also more attractive to the predatory mite, Phytoseiulus persimilis, than the
      latter. This shows that previous exposure of plants to volatiles from herbivore
      infested neighbors results in a stronger response of plants in terms of predator
      attraction when herbivores damage the plant. This supports the hypothesis that
      the downwind uninfested plant is actively involved. Both adsorption and
      production of volatiles can mediate the attraction of carnivorous mites to plants
      that have been exposed to volatiles from infested neighbors.

PMID- 15503522
TI  - Responses of female orange wheat Blossom midge, Sitodiplosis mosellana, to wheat
      panicle volatiles.
AB  - Air entrainment samples of volatiles from panicles of intact wheat, Triticum
      aestivum, cultivar 'Lynx' were collected at the ear emergence/early anthesis
      growth stage. In an olfactometer bioassay, both freshly cut panicles and an air
      entrainment sample were found to attract female orange wheat blossom midge
      adults, Sitodiplosis mosellana. Coupled gas chromatography-electroantennography
      (GC-EAG) analyses of panicle volatiles located six electrophysiologically active
      components. These were identified by coupled gas chromatography-mass spectrometry
      and coinjection with authentic standards, on polar and nonpolar GC columns, as
      acetophenone, (Z)-3-hexenyl acetate, 3-carene, 2-tridecanone, 2-ethyl-1-hexanol,
      and 1-octen-3-ol. Although none of these was active when presented individually
      at the levels present in the entrainment sample, acetophenone, (Z)-3-hexenyl
      acetate, and 3-carene were active in the olfactometer when presented at a higher
      dose of 100 ng on filter paper. However, the six-component blend and a blend of
      acetophenone, (Z)-3-hexenyl acetate, and 3-carene, in the same ratio and
      concentration as in a natural sample, was as attractive to female S. mosellana as
      the whole air entrainment sample.

PMID- 15503523
TI  - Volatiles production and attractiveness to the Mexican fruit fly of Enterobacter
      agglomerans isolated from apple maggot and Mexican fruit flies.
AB  - We investigated two strains of uricase (+) Enterobacter agglomerans, one isolated
      from the apple maggot fly (AMF) and one from the Mexican fruit fly (MFF), for 1)
      attractiveness to MFF, and 2) production of attractive chemicals. Regarding
      chemicals demonstrated attractive to the MFF, the MFF bacterial strain produced
      more 2,5-dimethylpyrazine, 2-phenylethanol, and indole than the AMF strain,
      whereas the AMF, but not the MFF strain, produced 3-hydroxybutanone. Cell types
      that predominated in plated subcultures varied from batch to batch resulting in
      variation in volatiles production, especially by the AMF strain where indole was
      sometimes a major component of the odor and at other times not detectable.
      Despite the greater production of attractive chemicals by the MFF strain, the AMF
      strain was consistently more attractive and the MFF strain was not different from
      uninoculated control plates. Statistical analyses indicated negative correlations
      of attractiveness with production of indole, 2,5-dimethylpyrazine, and 2
      phenylethanol, and positive correlation with 3-hydroxybutanone. Results support
      previous findings with the Mexican fruit fly that showed combinations of
      attractive chemicals sometimes are not attractive.

PMID- 15503524
TI  - Generalization of a habituated feeding deterrent response to unrelated
      antifeedants following prolonged exposure in a generalist herbivore, Trichoplusia
      ni.
AB  - The possibility of generalization of habituated response to unrelated feeding
      deterrents following prolonged exposure was examined in third instar Trichoplusia
      ni (Lepidoptera: Noctuidae) larvae by rearing them on antifeedants and then
      testing with other unrelated antifeedants. We introduced neonate larvae (< 24-hr
      old) onto cabbage leaves treated with crude seed extracts of Melia volkensii
      (Meliaceae) or oil of Origanum vulgare ("oregano") (Lamiaceae) and allowed them
      to feed until early in the third instar. Naive larvae were reared on cabbage
      leaves treated with carrier solvent alone. Both experienced and naive larvae were
      tested for feeding deterrent response with the same and the different extracts in
      a leaf disc choice bioassay. Habituation was generalized to both M. volkensii and
      oregano following prolonged exposure to either plant extract and also to a pure
      allelochemical, thymol, following prolonged exposure to either digitoxin or
      xanthotoxin. However, there was no generalization of the habituated response to
      oregano following prolonged exposure to digitoxin or thymol, or to thymol or
      xanthotoxin following prolonged exposure to oregano or M. volkensii. Our results
      demonstrate that habituated response to feeding deterrents in a polyphagous
      insect herbivore can be generalized among and between plant extracts and pure
      allelochemicals, but not in all situations. The implications of such behavioral
      plasticity in herbivorous insects for the use of antifeedants as crop protectants
      or for host plant shifts is discussed.

PMID- 15503526
TI  - Comparative capability to detoxify vegetable allelochemicals by larval
      mosquitoes.
AB  - In order to confirm the phytotoxicological basis for the ecological
      specialization of larval culicine fauna among different subalpine mosquito
      breeding sites, we compared the capability of six different Aedes larval taxa or
      populations of different ecological origin to detoxify dietary leaf litter
      originating from the environmental vegetation. Detoxification experiments were
      performed through in vitro digestion of a toxic leaf litter fraction using larval
      extracts as the enzymatic sources. Comparison of toxicological and detoxifying
      properties among the different larval samples indicates an association between
      their tolerance to leaf litter toxicants and their detoxification capability,
      which vary according to ecological origin. The fact that the detoxifying factor
      within the larval extracts appears to be a protein-like compound with a molecular
      weight bigger than 30 kDa suggests the possible involvement of detoxifying
      enzymes in larval tolerance to leaf litter toxicants. This is congruent with
      previous biochemical data that suggests the involvement of cytochrome P450
      monooxygenase and esterase activities in the detoxification process.

PMID- 15503525
TI  - Differential activity of peroxidase isozymes in response to wounding, gypsy moth,
      and plant hormones in northern red oak (Quercus rubra L.).
AB  - We measured total peroxidase activity and the activities of peroxidase isoforms
      in leaves of red oak (Quercus rubra L.) seedlings exposed to wounding and plant
      hormones in the greenhouse. Activity of specific peroxidase isoforms was induced
      differentially by gypsy moth wounding, mechanical wounding, and the wound
      associated plant hormone jasmonic acid. Activity of one isoform was enhanced
      modestly by treatment with salicylate. A study of peroxidase activity in
      naturally occurring galls elicited on red oak leaves by 12 hymenopteran and
      dipteran insect species found 16 POD isoforms, 11 of which were differentially
      induced or suppressed in galls compared with leaves. In both studies, total
      peroxidase activity as measured spectrophotometrically was not clearly related to
      activity of these isoforms. These results indicate that red oak seedlings and
      trees may respond specifically to wounding, particular insects, and plant signals
      through changes in the activities of individual isozymes.

PMID- 15503527
TI  - Structural diversity and defensive properties of norditerpenoid alkaloids.
AB  - We have tested the insect antifeedant and toxic activity of 43 norditerpenoid
      alkaloids on Spodoptera littoralis and Leptinotarsa decemlineata including
      eserine (physostigmine), anabasine, and atropine. Antifeedant effects of the test
      compounds were structure- and species-dependent. The most active antifeedants to
      L. decemlineata were 1,14-diacetylcardiopetaline (9) and 18-hydroxy- 14-O
      methylgadesine (33), followed by 8-O-methylconsolarine (12), 14-O
      acetyldelectinine (27), karakoline (7), cardiopetaline (8), 18-O
      demethylpubescenine (13), 14-O-acetyldeltatsine (18), takaosamine (21), ajadine
      (24), and 8-O-methylcolumbianine (6) (EC50 < 1 microg/cm2). This insect showed a
      moderate response to atropine. S. littoralis had the strongest antifeedant
      response to 24, 18, 14-O-acetyldelcosine (19), and delphatine (29) (EC50 < 3
      microg/cm2). None of the model substances affected the feeding behavior of this
      insect. The most toxic compound to L. decemlineata was aconitine (1), followed by
      cardiopetalidine (10) (% mortality > 60), 14-deacetylpubescenine (14), 18-O
      benzoyl-18-O-demethyl-14-O-deacetylpubescenine (17), 14-O-acetyldelcosine (19),
      14-deacetylajadine (25) and methyllycaconitine (30) (% mortality > 45). Orally
      injected S. littoralis larvae were negatively affected by 1, cardiopetaline (8),
      10, 1,14-O-acetylcardiopetalidina (11), 12, 14, 1,18-O-diacetyl-19-oxo
      gigactonine (41), olivimine (43), and eserine in varying degrees. Their
      antifeedant or insecticidal potencies did not parallel their reported nAChR
      binding activity, but did correlate with the agonist/antagonist
      insecticidal/antifeedant model proposed for nicotininc insecticides. A few
      compounds [14, tuguaconitine (38), 14-demethyldelboxine (40), 19,
      dehydrodelsoline (36), 18-O-demethylpubescenine (13), 41, 9, and delcosine (23)]
      had selective cytotoxic effects to ward insect-derived Sf9 cells. None were
      cytotoxic to mammalian CHO cells and none increased Trypanosoma cruzi mortality.
      The selective cytotoxic effects of some structures indicate that they can act on
      biological targets other than neuroreceptors.

PMID- 15503528
TI  - Creosote bush (Larrea tridentata) resin increases water demands and reduces
      energy availability in desert woodrats (Neotoma lepida).
AB  - Although many plant secondary compounds are known to have serious consequences
      for herbivores, the costs of processing them are generally unknown. Two potential
      costs of ingestion and detoxification of secondary compounds are elevation of the
      minimum drinking water requirement and excretion of energetically expensive
      metabolites (i.e., glucuronides) in the urine. To address these impacts, we
      studied the costs of ingestion of resin from creosote bush (Larrea tridentata) on
      desert woodrats (Neotoma lepida). The following hypotheses were tested: ingestion
      of creosote resin by woodrats (1) increases minimum water requirement and (2)
      reduces energy available by increasing fecal and urinary energy losses. We tested
      the first hypothesis, by measuring the minimum water requirement of woodrats fed
      a control diet with and without creosote resin. Drinking water was given in
      decreasing amounts until woodrats could no longer maintain constant body mass. In
      two separate experiments, the minimum drinking water requirement of woodrats fed
      resin was higher than that of controls by 18-30% (about 1-1.7 ml/d). We tested
      several potential mechanisms of increased water loss associated with the increase
      in water requirement. The rate of fecal water loss was higher in woodrats
      consuming resin. Neither urinary water nor evaporative water loss was affected by
      ingestion of resin. Hypothesis 2 was tested by measuring energy fluxes of
      woodrats consuming control vs. resin-treated diets. Woodrats on a resin diet had
      higher urinary energy losses and, thus, metabolized a lower proportion of the
      dietary energy than did woodrats on control diet. Fecal energy excretion was not
      affected by resin. The excretion of glucuronic acid represented almost half of
      the energy lost as a consequence of resin ingestion. The increased water
      requirement and energy losses of woodrats consuming a diet with resin could have
      notable ecological consequences.

PMID- 15503529
TI  - Endogenous free fatty acids repel and attract Collembola.
AB  - We used video recording of the movement pattern of Protaphorura armata
      (Collembola) to test whether its avoidance of the odor of dead conspecifics
      extends to related species. P. armata was repelled by the odor of dead
      individuals of Onychiurus scotarius and Onychiurus circulans, but not by live
      individuals. Free palmitic, oleic, and linoleic acids were present in extracts of
      the three repellent species, but only free palmitic acid was detected in extracts
      of a fourth nonrepellent species, Folsomia candida. Synthetic palmitic acid was
      attractive to P. armata, linoleic acid was repellent, and oleic acid gave no
      response. o. scotarius and O. circulans also contained 2,3-dimethoxy-pyrido[2,3
      b]pyrazine, known as a defense substance. We discuss the role of free fatty acids
      in predator avoidance, conspecifics attraction, and food recognition in P.
      armata.

PMID- 15503530
TI  - Oviposition deterrents in larval frass of four Ostrinia species fed on an
      artificial diet.
AB  - Behavioral bioassays have shown that volatile oviposition-deterring chemicals are
      present in the frass of Ostrinia zealis, O. furnacalis, O. scapulalis, and O.
      latipennis larvae fed on an artificial diet. These chemicals were extractable
      with acetone, and could be partitioned into a polar lipid fraction. This fraction
      mainly included palmitic, stearic, oleic, linoleic, and linolenic acids. No
      significant differences among the four Ostrinia species were found in the amount
      and composition of these free fatty acids. A mixture of the five authentic fatty
      acids of the composition found in the larval frass of O. zealis exhibited
      significant oviposition-deterring effects on all four species.

PMID- 15503531
TI  - Sex pheromones and reproductive behavior of Spodoptera litura (Fabricius) moths
      reared from larvae treated with four insecticides.
AB  - When Spodoptera litura (Fabricius) larvae were treated with the insecticides
      deltamethrin, endosulfan, malathion, and carbaryl at dosages causing 30%
      mortality (LD30), female moths reared from survivors showed similar patterns in
      the frequency of calling behavior. However, females reared from larvae dosed with
      deltamethrin had significantly higher titers of sex pheromone than those treated
      with endosulfan, malathion, or carbaryl, or control individuals. The ratio of the
      sex pheromone blend, Z9,E12-14:OAc to Z9,E11-14:OAc in females from the
      deltamethrin treatment group differed significantly from that of female moths in
      other treatments. In a wind-tunnel bioassay, males reared from larvae treated
      with deltamethrin, malathion, or carbaryl were less likely to display behaviors
      resulting in the location of a sex pheromone source than males reared from larvae
      treated with endosulfan or a solvent control (acetone). Mating success was
      significantly decreased in pairs containing either males or females reared from
      larvae that survived treatment with deltamethrin.

PMID- 15503533
TI  - [Is there a lasting effect of functional claw-trimming on claw conditions?].
AB  - The influence of regular claw-trimming on the occurrence and prevalence of claw
      disorders was examined on a total of 164 dairy cows (Simmental, Red Friesian,
      Holstein Friesian). Ten dairy farms in the Austrian province of Salzburg were
      used for this study. Three examinations of the claws were carried out with an
      interval of six months in between to find out claw disorders. The results were
      recorded according to a claw scoring system. The claw scores were in the range of
      other studies using the same scoring system. The median of the claw scores at the
      beginning of the study was 27 in the tied stall group compared with 37 in the
      loose housing group, remaining at that level in the first group and falling to 25
      in the second group. All in all, the positive effect of regular claw trimming was
      more pronounced in the loose housing group than in the tethered housing group.

PMID- 15503532
TI  - Chemical interactions of Brachiaria plantaginea with Commelina bengalensis and
      Acanthospermum hispidum in soybean cropping systems.
AB  - Previous results obtained in soybean-wheat rotations under no-tillage conditions
      showed reductions in the seedbank of the weed species Commelina benghalensis, but
      no alteration in the seedbank of Acanthospermum hispidum in areas infested with
      Brachiaria plantaginea. Analyses of the soluble fraction of B. plantaginea
      indicated the predominance of aconitic acid (AA) among the aliphatic acids and
      ferulic acid (FA) among the phenolic acids. Laboratory bioassays using C.
      benghalensis and A. hispidum were carried out to evaluate phytotoxic effects of
      pure organic acid solutions and dilute extracts of B. plantaginea on seed
      germination, root development, and fungal germination. Solutions of AA and FA
      were prepared at 0.25, 0.50, and 1.0 mM. Extracts of B. plantaginea were diluted
      to obtain concentrations of AA similar to those in the prepared solutions. Seeds
      were sown on 0.5% agar (containing AA, FA, or diluted extract) in plastic-covered
      receptacles and maintained in a germination chamber for 10 days. AA and FA
      solutions and the B. plantaginea extract reduced germination and root length,
      mainly of C. benghalensis. AA also stimulated the development of endophytic fungi
      (Fusarium solani), which had complementary adverse effects on C. benghalensis
      germination. FA and AA may play important roles in reducing the seedbank of some
      weed species, acting directly on germination and development and, indirectly, by
      stimulating endophytic fungi that alter germination.

PMID- 15503534
TI  - [Influence of prion protein gene polymorphisms on performance traits in German
      meat sheep breeds].
AB  - PrP polymorphisms influence the scrapie susceptiblility of sheep. The objective
      of this study was to analyse the association between performance traits and the
      PrP genotype in the sheep breeds German black-headed and German white-headed
      mutton, Bleu du Maine, German mutton merino, Leine, Texel and Suffolk from Lower
      Saxony and Westphalia. We analysed performance traits such as scores for muscle
      mass, type and wool quality and the calculated daily weight gain using linear
      animal models. In all seven breeds no statistically significant associations were
      found between performance traits and the occurrence of ARR alleles, and the
      ARR/ARR genotypes, respectively. All genotyped sheep of all breeds investigated
      showed significantly superior performance traits in comparison to the non
      genotyped animals.

PMID- 15503535
TI  - [Relationship between morphological characteristics of the teat duct and
      prevalence of intramammary infections with Streptococcus agalactiae in dairy
      cows].
AB  - The objective of the study was to determine the relationship between
      morphological findings of the surface of teat duct particularly the level of
      ceratosis and the prevalence of intramammary infections (IMI). The study was
      conducted on a commercial dairy herd housing about 3000 lactating dairy cows. We
      examined 891 quarters in the middle of lactation. Duplicate samples of quarter
      foremilk were collected monthly. The bacteriological status of quarters was
      determined according to the recommendations of IDF. At the same time teats were
      evaluated by clinical examinations. The appearance of teat skin lesions and the
      status of the teat duct especially the existence of hyperceratosis (HC) was
      documented. Four classes of teat duct hyperceratosis were defined: without,
      slight, medium and severe HC. The rate of IMI in different classes of
      hyperceratosis of teat duct was compared by Chi-square analysis. Prevalences of
      intramammary infections were determined three times (P1, P2 and P3) during the
      study period. Prevalence of infection was high for S. aureus (P1: 5.6% vs. P2:
      4.5% vs. P3: 4.3%), Sc. agalactiae (P1: 2.7% vs. P2: 2.6% vs. P3: 2.8%) and CNS
      (P1: 10.7% vs. P2: 8.8% vs. P3: 9.6%). Furthermore we detected IMI caused by
      other streptococci, yeast, E. coli and mixed infections. A positive correlation
      between status of HC and prevalence of IMI for Sc. agalactiae was found. At the
      second and third sampling time the rate of intramammary infection with Sc.
      agalactiae in quarters with medium HC (P2: 9.21% and P3: 13.73%) differed
      significantly (p < 0.05) compared to groups without (P2: 1.56% and P3: 1.91%) and
      slight hyperceratosis (P2: 2.33% and P3: 2.56%). The results of our study
      indicate a correlation between morphology of teat duct surface, especially
      regarding to Sc. agalactiae. On one hand HC can cause high intramammary infection
      rate with Sc. agalactiae. On the other hand it is possible that HC is the
      consequence of a quarter infection with Sc. agalactiae. Further research is
      required.

PMID- 15503536
TI  - Fumonisin B1 causes multiple lesions in common carp (Cyprinus carpio).
AB  - Year-1 carp were fed ratios containing 100mg/kg and 10 mg/kg of added fumonisin
      B1 for 42 days. The experimental and control fish were examined clinically during
      the experiment and at the end all fish were necropsied and histological changes
      recorded. Blood vessels, liver, exocrine and endocrine pancreas, excretory and
      haematopoietic kidney, heart and brain were sensitive both to 100 and 10mg/kg of
      FB1 in the diet and the rodlet cell (RC) frequency was considerably increased in
      and around damaged tissues. Many damaged blood vessels contained stacks of RCs
      above the endothelium. Other changes subsequent to fumonisin exposure that have
      not been previously reported include scattered lesions in the exocrine and
      endocrine pancreas, and interrenal tissue, probably due to ischemia and/or
      increased endothelial permeability. Presented findings indicate the need for more
      intensive studies of fumonisin-induced toxicity in cultured fish.

PMID- 15503537
TI  - [Pigs led by rope].
AB  - Up to the midth of the 20th century in central europa single pigs were led by a
      rope, fixed on a hindleg. This technique can be proved back by pictures to
      antique. As shown by several illustrations this form was customary during Middle
      Ages and later.

PMID- 15503538
TI  - [Genetic analysis of the prevalence of abomasal displacement and its relationship
      to milk output characteristics in German Holstein cows].
AB  - Genetic parameters for the prevalence of abomasal displacement and for milk yield
      traits were estimated using a data set of 3578 cows. The animals originated from
      50 farms near Hanover being under the official milk recording scheme. At these
      farms all cases of abomasal displacement in German Holsteins were registered from
      July 2001 to January 2003. Using REML heritability estimates in linear animal
      models were h2 = 0.034 +/- 0.014, h2 = 0.017 +/- 0.013 and h2 = 0.029 +/- 0.011
      for all cases of abomasal displacement, leftsided abomasal displacement and
      rightsided abomasal displacement, respectively. Additive genetic correlations
      between all cases of abomasal displacement and milk yield traits were small,
      ranging from rg = -0.20 (fat content) to rg = 0.08 (milk kg). However, there was
      a highly positive additive genetic correlation between leftsided abomasal
      displacement and milk yield of rg = 0.683 +/- 0.227. Leftsided abomasal
      displacement was correlated additive genetically to fat and protein yield, fat
      and protein content with rg = 0.595 +/- 0.297, r9 = 0.653 +/- 0.250, rg = -0.768
      +/- 0.3280 und rg = -0.643 +/- 0.354, respectively. The additive genetic
      correlation to the ratio between fat and protein content was rg = -0.585 +/-
      0.470. For rightsided abomasal displacement, additive genetic correlations were
      of similar size but with reversed signs. The estimates obtained for the residual
      correlations were negligibly small throughout.

PMID- 15503539
TI  - [Case report: aortic valve endocarditis in a horse].
AB  - A case of endocarditis of the aortic valve in a 11 year old thoroughbred is
      presented. Diagnostic approach, the value of echocardiography, and the various
      symptoms, complications and prognosis are discussed. The horse with ruptured
      aortic valves due to endocarditis with severe aortic and mitral regurgitation
      causing congestive heart failure, was euthanised due to bad prognosis.

PMID- 15503540
TI  - [Case report--bilateral anotia in a German Holstein calf].
AB  - In a female black and white coloured German Holstein calf bilateral anotia and
      impaired vision was observed. This congenital anomaly is very seldomly seen in
      cattle. The clinical examination revealed no further anomalies. The test on a
      BVDV infection was negative. No other affected calves could be detected by
      examining the relatives.

PMID- 15503541
TI  - Measuring the quality of breast cancer care in women.

PMID- 15503542
TI  - Apical problems--coronal solutions: how changes in access cavity design can
      prevent and overcome problems with curved canals.
AB  - There is no doubt that the preparation of curved canals presents one of the
      greatest challenges in endodontic and is fraught with potential difficulties.
      Canal curvature can only be seen on a radiograph in the mesio-distal plane and
      yet it is well known that curvature in the bucco-lingual plane is also evident in
      many teeth. A primary cause of failure of endodontic treatment is the persistence
      of microbial infection. In curved canals this is often due to procedural errors
      such as ledges, fractured instruments and canal blockage. Over the years a
      variety of techniques have been proposed for preparing these canals. Whether it
      is the straightforward endodontic treatment of a straight, single rooted tooth,
      or retreatment of a curved molar with a number of procedural errors, the access
      cavity has a crucial role in the achievement of successful endodontic treatment.
      The size and shape of the access cavity will be dictated by the degree of
      curvature of the canals and the objectives that have to be achieved.

PMID- 15503543
TI  - Amalgam tattoo (amalgam pigmentation) of the oral mucosa: clinical
      manifestations, diagnosis and treatment.
AB  - Amalgam tattoo is an iatrogenic lesion caused by traumatic implantation of dental
      amalgam into soft tissue. Amalgam tattoo is the most common localized pigmented
      lesion in the mouth. In a study of a mass screening oral examination in the
      United States, it was found in about 0.4-0.9% of the adult population and in
      Sweden in about 8%. Clinically, amalgam tattoo presents as a dark gray or blue,
      flat macule located adjacent to a restored tooth. Most are located on the gingiva
      and alveolar mucosa followed by the buccal mucosa and the floor of the mouth.
      Microscopic examination reveals that amalgam is present in the tissues in two
      forms: as irregular dark, solid fragments of metal or as numerous, discrete fine,
      brown or black granules dispersed along collagen bundles and around small blood
      vessels and nerves. In most lesions, it is presented in both forms. The biologic
      response to the amalgam is related to particle size, quantity and elemental
      composition of the amalgam. Large fragments often become surrounded by dense
      fibrous connective tissue. Smaller particles are associated with mild to moderate
      chronic inflammatory response with individual macrophages engulfing small amalgam
      particles. Occasionally, the reaction takes the form of foreign body granuloma in
      which macrophages and multinucleated giant cells are present. Some of the
      multinucleated giant cells also contain amalgam particles. Diagnosis of amalgam
      tattoo is usually obvious from the location and clinical appearance. A radiograph
      is recommended to confirm the presence of metallic particles, but absence of
      radiographic evidence does not rule out the possibility, since particles are
      often too fine or widely dispersed to be visible on radiographs. When there is no
      radiographic evidence or an adjacent restored tooth, biopsy is recommended to
      rule out an early melanoma. Once the diagnosis of amalgam tattoo has been
      established, no additional treatment is necessary except for cosmetic reasons. If
      the pigmentation is cosmetically unacceptable, surgical excision and
      transplantation of oral mucosal tissue has been suggested. Q-switched ruby laser
      and Q-switched alexandrite laser have also been used with favorable results.

PMID- 15503544
TI  - [Potential risks, adverse effects and drug interactions associated with herbal
      medicine in dental patients].
AB  - Herbal medicine is an increasingly common form of alternative therapy in the
      United States. Most herbal products are considered dietary supplements and thus
      are not regulated as medicines. They are marketed without prior approval of their
      efficacy and safety by the Food and Drug Administration (FDA). Some herbal
      medications have potentially harmful side effects as well as adverse interactions
      with conventional drugs. The adverse reactions involve all systems, age groups
      and severity. It is important for dentists and other health care providers to
      obtain adequate information as to what herbal medications their patients are
      taking. It is also necessary for professionals to acquire knowledge regarding
      herbal medications as to their use and to educate their patients about the risk
      benefit and potential interactions these medications may have with over-the
      counter and prescription drugs. The purpose of this article was to review the
      literature on the potential risks of commonly used herbal medications: Ginkgo
      Biloba, St. John's Wort, Ginseng, Echinacea, Saw Palmetto, Garlic, Kava and
      Ephedra.

PMID- 15503545
TI  - [Oral health promotion for children in boarding schools].
AB  - INTRODUCTION: In Israel there are approximately 9,000 "sheltered" children who
      are lodged in several boarding schools. These children have been removed from
      their parents' guardianship, some with their parents permission and some by court
      order, usually due to neglect or abuse. This article describes these children and
      the efforts implemented regarding oral health: dental care insurance, a
      preventive program which has been conducted for approximately 10 years among 80
      boarding schools and family care shelters, evaluation of these services and
      caries levels among the children. METHODS: A sample of 123 children was examined
      in four Israeli boarding schools. The DMF(T) index was employed according to WHO
      guidelines, by one examiner, using a torch, plane dental mirror and probe when
      required. RESULTS: An average DMF(T) level of 4.62 was detected among 12 year
      olds. Among all the children from ages 1-18 years, only 30% were caries free. The
      rate of caries-free children decreased with age. CONCLUSIONS: Caries prevalence
      among this population was higher than levels reported in Israel and abroad. There
      is a clear need for oral health promotion among this community.

PMID- 15503547
TI  - [Risk factors for dental implant inflammation--a literature review].
AB  - Replacing missing teeth with osseointegrated dental implants is a predictable
      technique as evidanced by overall 5-years survival rate that range between 93% to
      97%. Few studies, however have adressed the history and frequency of inflammatory
      complication associated with dental implant. Inflammatory complications are the
      main cause of failure of dental implants. In this review we classified the
      inflammatory complications to acute and chronic and to those limited to the hard
      tissue, to the soft tissue or both. The incidence of the complications is
      discussed with an emphasis on their risk factors.

PMID- 15503546
TI  - [New treatment protocols for avulsed teeth].
AB  - Traumatized teeth present a clinical challenge with regard to their diagnosis,
      treatment plan and prognosis. The injuries to the permanent dentition include
      crown and root fractures, subluxations, luxations and tooth avulsion. Common
      complications are pulp necrosis, periapical pathosis and root resorption. This
      article will describe new clinical modalities for the treatment of avulsed teeth
      and discuss the rational for their use.

PMID- 15503548
TI  - [Disciplinary action and its degree of implementation].
AB  - The aim of disciplinary action against dental practitioners is to uphold
      professional standards, to protect the safety of the patients and to maintain
      public confidence in the profession. Disciplinary action against dentists in
      Israel is based on the Dentists' Ordinance of 1979. The main principle behind
      disciplinary action is trial by peers, which in effect means that the profession
      upholds the required standards. Seven examples are mentioned in the law for which
      the Ministry of Health can reprimand or suspend the license of a dentist
      permanently or for a limited period of time. The panel for disciplinary action
      consists of three judges: one lawyer and two dentists--one (the chairman)
      represents the General Director of the Ministry of Health, the other represents
      the Israel Dental Association. This article deals with the form of legal
      discussion, types of punishment and their limitations as interpreted by the
      authors. All 26 complaint files presented to the disciplinary committees between
      1997-2002 that were concluded are discussed. The accusations, as well as the
      verdicts, are listed.

PMID- 15503549
TI  - [A new gel for topical use in treating severe periodontal disease--clinical
      observations].
AB  - Within the framework of the efforts to find non-invasive treatment methods for
      severe periodontitis, a topical gel was developed by an Israeli research group.
      The aim of the current study is to present clinical observations and X-ray
      measurements of alveolar bone changes following an 8 week, self-care periodontal
      treatment in two groups of patients with severe periodontitis. All 31 patients
      who participated in the study showed an improvement of the periodontal condition
      as expressed in all the indexes examined. The observation findings testify to the
      fact that through self-care using a topical gel, significant results were
      achieved: decrease in probing depth, decrease in bleeding, significant
      improvement in teeth mobility and in level of the alveolar bone height and its
      density. These clinical findings raise interesting research questions and hint at
      the potential for regeneration of supportive periodontal tissues in cases of
      severe periodontitis, currently achieved only through surgical means. In order to
      obtain more accurate data regarding the treatment potential of this gel, it is
      important to conduct additional controlled clinical trials on different
      populations and also to try and determine how it works.

PMID- 15503550
TI  - The dentist--a personal and family doctor.

PMID- 15503551
TI  - [Acute phase reaction and immunocompetence in sepsis and SIRS].
AB  - The incidence of sepsis and SIRS, respectively is still rising. Mortality is 40
      to 70% and, thus, remains very high in spite of major advances in intensive care
      medicine. Numerous experimental data have helped to explain isolated aspects of
      the pathophysiology of these disease states but the complex patho-mechanism
      remains to be elucidated. The discovery of the toll-like receptors and of the
      endotoxin-binding proteins LBP and BPI have substantially contributed to the
      understanding of the bacterial toxin-host interactions and may stimulate the
      development of new therapeutic strategies in the future. Pro- and anti
      inflammatory cytokines play a central role in disease evolution, however the
      concept of organ-derived and organ-specific damage is gaining importance. Both
      inflammation and counter-regulation can occur at the same time in the circulation
      thus, making the evaluation of the patients' immunological status difficult.
      Additionally, several gene polymorphisms have been detected for example within
      the toll-like receptor genes and TNF genes. These polymorphisms document the
      existence of pre-disposing factors, which influence acute phase reaction as well
      as immuno-competence in sepsis. Both genes and gender will play an important role
      in the future to identify patients at risk and potentially, to design a specific
      and individualized immuno-therapies.

PMID- 15503553
TI  - Rationale for using microbiological diagnosis as an adjunct to periodontal
      treatment.

PMID- 15503552
TI  - [Cortisol in critically ill patients with sepsis--physiological functions and
      therapeutic implications].
AB  - Modern immunology reveals that cortisol interacts with the immune response at
      virtually all levels exerting suppressive and permissive effects. A prerequisite
      for the defense of severe infections is the functional integrity of the
      hypothalamic-pituitary-adrenal axis (HPAA) resulting in adequate cortisol
      production. There is increasing evidence that cortisol physiology and regulation
      substantially change in the course of septic shock. Patients with septic shock
      may suffer from relative adrenocortical insufficiency resulting in a relative
      deficiency of cortisol. In addition, the number and the affinity of cellular
      glucocorticoid receptors are decreased which may reduce the cortisol action at
      the cellular level. Since septic shock and adrenal insufficiency are sharing
      hemodynamic abnormalities such as hyperdynamic shock and peripheral vasodilation,
      the administration of stress doses of hydrocortisone appears to be a rational
      therapeutic approach in patients with septic shock. Controlled studies reveal
      that stress doses of hydrocortisone attenuate the systemic inflammatory response.
      Recently, two double-blind studies demonstrated that stress doses of
      hydrocortisone given in patients with septic shock reduce the time to shock
      reversal. The most important hemodynamic effect was an increase in the systemic
      vascular resistance. The earlier weaning from vasopressor therapy was associated
      with a trend towards improvements in organ dysfunction and mortality,
      respectively. Large-scale trials are on the way to investigate the benefit of
      stress doses of hydrocortisone on mortality of septic shock. This paper will
      focus on changes in glucocorticoid physiology and regulation during septic shock
      and will discuss the effects of stress doses of hydrocortisone on immune response
      and vascular tone in the course of septic shock.

PMID- 15503554
TI  - Endodontic management of curved canals in posterior teeth.

PMID- 15503555
TI  - International externships for senior students at the School of Dental Medicine.

PMID- 15503556
TI  - Generations of doctors Weiss.

PMID- 15503557
TI  - The real issue of health care reform.
AB  - Perhaps a better title would be, Health Care Reform: Does it affect dentistry?
      This query arises because only one of the major legislative proposals includes
      dentistry to any significant degree and as of now the American Dental Association
      is opposed to the inclusion of dentistry (except for indigent children) in Health
      Care Reform. Of course, however, the answer to this question is yes. The
      suggested legislation will bring about changes of such magnitude that dentistry
      can't avoid their influence. We will briefly outline the main issues involved in
      health care reform and summarize what the proposals mean for dentistry.

PMID- 15503558
TI  - Periodontal diagnostics.

PMID- 15503559
TI  - Community relations.

PMID- 15503560
TI  - 63 years in retrospect: an interview with Mr. Joseph Flowers.

PMID- 15503561
TI  - The sixties generation.

PMID- 15503562
TI  - Primary care management of maxillofacial injuries in sports.
AB  - Injuries to the maxillofacial region sustained in sports related trauma are
      increasing in the United States. The pediatric (age 12 and younger) and teenage
      populations account for the greatest number of these injuries primarily due to
      increased team sports participation in these younger age groups. A severe injury
      to the maxillofacial region can have devastating psychological effects as well as
      being physically debilitating. Therefore, early treatment of soft tissue and bony
      injuries will minimize scarring and decrease potentially adverse psychological
      implications. Sports trauma is a frequent source of maxillofacial injuries
      especially in the younger population. Basic protective equipment, such as proper
      fitting helmets, mouth guards and face masks, are still not mandatory, or rules
      not enforced, in many youth hockey and football leagues. In addition, the
      increased popularity of multispeed bicycles, dirt bikes, and off-road vehicles
      (e.g. snowmobiles, go-carts) in the hands of unrestrained and unprotected
      children and adolescents has contributed to an increasing number of maxillofacial
      injuries in these groups.

PMID- 15503563
TI  - Current issues in the neurology and genetics of learning-related traits and
      disorders: introduction to the special issue.

PMID- 15503564
TI  - Genotype-environment correlations for language-related abilities: implications
      for typical and atypical learners.
AB  - Recent behavioral genetic research has shown that genetic propensities are
      associated with individual differences in experiences, and thus, what may appear
      to be environmental effects can reflect genetic influence. This study examines
      passive genotype-environment correlations (GECs) for language-related abilities
      by comparing environment-child language associations in adoptive and nonadoptive
      families. The results provide evidence for the genetic mediation of the
      association between home environmental variables, such as the provision of toys
      and games, maternal involvement, and degree of intellectual/cultural orientation
      with children's language-related abilities. Developmental changes in passive GECs
      are considered, and the implications for typical and atypical learners are
      discussed.

PMID- 15503565
TI  - Emerging issues in the genetics of dyslexia: a methodological preview.
AB  - A review of the classic and recent evidence on the genetics of reading disability
      (RD) shows encouraging progress, and accumulating evidence of genetic risk
      factors that operate within families and are separately localizable to more than
      one chromosomal region. The accelerating pace of these findings, however,
      suggests the need to consider some methodological issues about the design and
      interpretation of current and future studies. A major issue is the shape of the
      distribution of reading ability in the population, and we offer three tests of
      increasing rigor for determining whether those distributions are categorical, and
      hence not suitable for analyses that depend on the assumption of a continuous
      normal distribution. These tests are as follows: a nonnormal preponderance of
      cases with RD (i.e., the hump in the lower end of the distribution); a difference
      in the within-group variance-covariance matrices for typical readers compared to
      those with RD; and a correlation between a neurogenetically relevant criterion
      and a categorical reading variable that is larger than the correlation between
      the same criterion and a continuous version of the same reading variable. We
      emphasize also the importance of interactive relationships between multiple
      genetic loci, the variations in genotypic range as well as type of affectedness,
      the need to account for remediation variance, and the importance of lifespan
      changes in the phenotypes.

PMID- 15503566
TI  - Reading disability and chromosome 6p21.3: evaluation of MOG as a candidate gene.
AB  - Linkage analysis has localized a gene influencing specific reading disability
      (dyslexia) to 6p21.3. The myelin oligodendrocyte glycoprotein (MOG) gene, which
      maps to this region, was selected as a candidate. Myelin oligodendrocyte
      glycoprotein is a membrane protein, a member of the immunoglobin superfamily,
      that is found on the outermost lamellae of mature myelin. Although the exact
      function of this protein is unknown, its presence in the central nervous system
      and the hypothesized relationship between dyslexia and temporal processing rate
      as well as a suggested relationship with intelligence made this gene a candidate
      for dyslexia. Analysis of the coding exons and adjacent splice sites in a subset
      of 22 children with dyslexia from 10 sibships found a missense mutation in exon 4
      in 2 of the sibships. This change from the published sequence also occurred in 86
      of 96 random controls, making it considerably less frequent in this small sample
      of individuals with dyslexia. Subsequent typing of this single nucleotide
      polymorphism (SNP) in 74 nuclear families in which at least one child had reading
      disability showed no significant difference in frequency from the controls,
      however. Sib-pair linkage analysis with these families did not show significant
      linkage with the SNP nor with a separate polymorphic dinucleotide repeat marker
      in the MOG gene (MOG31/32), but association analysis identified two alleles of
      MOG31/32 that were associated with reading disability phenotypes with a low level
      of significance. Thus, although alleles in the MOG gene may be in linkage
      disequilibrium with a locus that contributes to reading disability, it is
      unlikely that the MOG gene itself is involved.

PMID- 15503567
TI  - Math learning disability and math LD subtypes: evidence from studies of Turner
      syndrome, fragile X syndrome, and neurofibromatosis type 1.
AB  - The present study examined whether indicators of math learning disability are
      observed in 5- and 6-year-olds with neurofibromatosis type 1 (NF1) and in 5- to 6
      year-old girls with Turner syndrome or fragile X syndrome. Data from 14 girls
      with Turner syndrome, 9 girls with fragile X syndrome, and 11 children with NF1
      were compared to data from control participants matched on age, sex, IQ score,
      and grade level. The results indicate that girls with fragile X syndrome or
      Turner syndrome are significantly more likely to have specific math difficulties
      relative to their control group, with a larger effect size demonstrated by the
      group with Turner syndrome. Young children with NF1 had a heterogeneous profile
      not suggestive of specific math disability. The results are discussed in terms of
      their implications for understanding math disability subtypes and the
      identification of math difficulty in the early school years.

PMID- 15503568
TI  - Event-related potentials and consonant differentiation in newborns with familial
      risk for dyslexia.
AB  - We measured event-related potentials (ERPs) to synthetic consonant-vowel
      syllables (/ba/, /da/, /ga/) from 26 newborns with familial risk for dyslexia and
      23 control infants participating in the Jyvaskyla Longitudinal Study of Dyslexia.
      The syllables were presented with equal probability and with interstimulus
      intervals ranging from 3,010 to 7,285 ms. Analyses of averaged ERPs from the
      latencies identified on the basis of principal component analysis (PCA) revealed
      significant group differences in stop-consonant processing in several latency
      ranges. At the latencies of 50-170 ms and 540-630 ms, the responses to /ga/ were
      larger and more positive than those to /ba/ and /da/ in the right hemisphere in
      the at-risk group. Between 740 and 940 ms, the responses to /ba/ and /da/
      differed between anterior and posterior electrode sites in the control group.
      These results indicate that the cortical electric activation evoked by speech
      elements differs between children with and without risk for dyslexia even
      immediately after birth. Group-related effects at early and late latency ranges
      of ERPs suggest differences both in the early sound processing based on
      activation of afferent elements and in later phases of syllable encoding.

PMID- 15503569
TI  - Newborn and preschool predictors of second-grade reading scores: an evaluation of
      categorical and continuous scores.
AB  - This study examined how the development of foundation skills in speech
      perception, language, short-term memory, and family demographics and activities
      in the home environment influence the development of reading skills. Data from 96
      children participating in a longitudinal research project were used. It was
      hypothesized that measures of specific foundation skills in the preschool period
      and measures of family demographics and home environment could be used to
      identify children's reading abilities. As expected, most of the foundation skills
      were found to be related to and predictive of reading scores. Event-related
      potential (ERP) measures of speech perception, which have previously been found
      to be predictive of reading abilities, and measures of family and home activities
      and language measures were related to reading scores. Verbal short-term memory
      scores contributed little to the prediction of reading scores. These variables
      influenced the results whether they were used to discriminate reading groups or
      to predict a continuum of reading scores, but there were large differences in the
      amount of variance accounted for. More variance was accounted for in the group
      analyses than in the continuum analyses.

PMID- 15503570
TI  - The term comorbidity is of questionable value in reference to developmental
      disorders: data and theory.
AB  - Over the last decade, there has been an enormous increase in the number of
      studies evaluating the overlap of developmental syndromes or disorders in both
      children and adults. This overlap of symptoms is often referred to as
      comorbidity, a term we criticize in this article because of its unsubstantiated
      presumption of independent etiologies. The premise of this article is that
      discrete categories do not exist in real life, and that it is misleading to refer
      to overlapping categories or symptoms as "comorbidities." We illustrate our point
      by presenting data from 179 school-age children evaluated with rigorous research
      criteria for seven disorders: reading disability (RD), attention
      deficit/hyperactivity disorder (ADHD), developmental coordination disorder (DCD),
      oppositional defiant disorder (ODD), conduct disorder (CD), depression, and
      anxiety. Fully 50% of this sample met the criteria for at least two diagnoses.
      The children with ADHD were at higher risk of having at least a second disorder
      compared to the children with RD. Overall, the high rates of overlap of these
      behavioral, emotional, and educational deficits in this broadly ascertained
      sample support the idea that the concept of comorbidity is inadequate. We discuss
      the concept of atypical brain development as an explanatory idea to interpret the
      high rate of overlap of developmental disorders.

PMID- 15503571
TI  - The neurobiological basis of reading.
AB  - The results from studies using positron emission tomography (PET) and functional
      magnetic resonance imaging (fMRI) in adults have largely revealed the involvement
      of left-hemisphere perisylvian areas in the reading process, including
      extrastriate visual cortex, inferior parietal regions, superior temporal gyrus,
      and inferior frontal cortex. Although the recruitment of these regions varies
      with the particular reading-related task, general networks of regions seem to be
      uniquely associated with different components of the reading process. For
      example, visual word form processing is associated with occipital and
      occipitotemporal sites, whereas reading-relevant phonological processing has been
      associated with superior temporal, occipitotemporal and inferior frontal sites of
      the left hemisphere. Such findings are evaluated in light of the technical and
      experimental limitations encountered in functional brain imaging studies, and the
      implications for pediatric studies are discussed.

PMID- 15503572
TI  - More power to them--statistically, that is: a commentary on Studdert-Kennedy,
      Mody, and Brady's criticism of a critique.
AB  - The power analysis discussed above establishes that it was most unlikely that
      Mody et al. (1997) could make a meaningful test of the Tallal hypothesis because
      of inadequate n and failure to specify the effect size. Note that this is a best
      case scenario, because the power analysis assumes that the analysis of variance
      assumptions were within reasonable boundaries (e.g., as specified by Norton's
      study). This was clearly not the case. In summary, the Mody et al. study fails to
      meet minimal scientific criteria and makes no meaningful contribution to the
      literature.

PMID- 15503573
TI  - Do ability and reading achievement correlate?

PMID- 15503574
TI  - Association of Educational Therapists: position paper on the SAT.
AB  - The Association of Educational Therapists supports the position that when the
      Scholastic Aptitude Test (SAT) is administered, the option of extended time
      should be available for all students.

PMID- 15503575
TI  - Substance abuse and LD. Introduction.

PMID- 15503576
TI  - Substance use disorders in young adults with and without LD: predictive and
      concurrent relationships.
AB  - This article reports on young people with and without learning disabilities (LD)
      and substance use disorders (SUD). Participants were assessed for LD at ages 12
      and 19 and for SUD and psychiatric disorders at age 19. Participants with LD at
      ages 12 and 19 were more likely to develop an SUD or a psychiatric disorder
      compared to participants without consistent LD. Participants with LD at age 19
      were more likely to have a concurrent SUD or psychiatric disorder compared to
      those without LD at age 19, while participants with LD at age 12 showed only a
      trend toward increased rates of SUD at age 19 when compared to participants
      without LD at age 12. Participants with and without LD did not differ in
      substance use, consumption levels, or onset history. In a multivariate model,
      adolescent LD was associated with a three-fold increased risk for SUD after
      behavioral problems and family structure had entered the model. Although these
      results provide some support for the notion that adolescents with LD are at
      increased risk for SUD, LD also appears to confer a general risk for adverse
      outcomes.

PMID- 15503578
TI  - Risk factors for adolescent substance abuse.
AB  - Reviews research on risk factors for adolescent substance use disorders (SUD) and
      discusses possible relationships between SUDs and learning disabilities (LD).
      Individual level factors (genetic, biologic, other familial, and psychiatric)
      emerge as very important in the risk equation, as well as the interaction between
      individual risk and environmental conditions. Commonalities between SUD risk and
      LD include prenatal substance exposure, family history of SUD, conduct disorder,
      social skills deficits, and academic failure; however, further research is needed
      to establish whether individuals with LD face a specific risk for SUDs, and if
      so, what the nature of that risk might be.

PMID- 15503577
TI  - Substance use, substance abuse, and LD among adolescents with a childhood history
      of ADHD.
AB  - A clinic-referred sample of 109 children with attention-deficit/hyperactivity
      disorder (ADHD) was followed into adolescence for the ascertainment of alcohol
      and other drug use and abuse. Learning disability (reading or math) in childhood
      was examined as a predictor of adolescent substance use and substance use
      disorder for alcohol and marijuana. No statistically significant group
      differences for children with LD versus those without LD emerged even after using
      different methods to compute LD. IQ/achievement discrepancy scores were similarly
      not predictive of later use or abuse. However, children with ADHD who had higher
      IQs and higher levels of academic achievement in childhood were more likely to
      try cigarettes, to smoke daily, and to have their first drink of alcohol or first
      cigarette at an early age. Children with ADHD who had higher reading achievement
      scores were less likely to have later alcohol use disorder. Although these
      findings are necessarily preliminary, due to the small number of children
      interviewed, the pattern of results suggests that level of cognitive functioning-
      rather than discrepancy between IQ and achievement--is important for the
      prediction of later substance use and abuse, at least in this clinic-referred
      sample of children with ADHD. Further, different mechanisms of risk related to
      cognitive functioning may be operating for experimentation with legal drugs such
      as alcohol and tobacco, regular cigarette smoking, and problematic alcohol use.

PMID- 15503579
TI  - Risk and resilience for substance abuse among adolescents and adults with LD.
AB  - Substance abuse is a major problem affecting the health and well-being of many
      people in our society. Although anecdotal evidence concerning linkages between
      learning disabilities (LD) and substance abuse has been common, this association
      is not well documented or understood. This article reviews the current research
      on substance abuse for adolescents and adults with LD, interpreting findings
      within a risk and resilience framework. Integrating these studies with the
      broader literatures on substance abuse and the needs of individuals with LD, the
      author develops hypotheses regarding specific risk and protective factors that
      could affect the occurrence of substance abuse for adolescents and adults with
      LD. Potential risk factors include a poor understanding of one's disability, a
      lack of skills for developing peer relationships, and the need for prolonged
      family support. Future directions for research in relation to prevention of and
      intervention regarding substance abuse among individuals with LD are discussed.

PMID- 15503580
TI  - Temporal resolution of auditory perception in relation to perception, memory, and
      language skills in typical children.
AB  - This study examined temporal resolution of auditory perception (TRAP) in relation
      to speech perception and phonological working memory in one experiment and in
      relation to measures of rapid naming, understanding of grammatical contrasts, and
      phonological awareness in a second experiment. In the TRAP test, 6- to 9-year-old
      children discriminated four pairs of two sine tones, 878 Hz and 1350 Hz,
      presented in blocks with stepwise decreasing interstimulus intervals from 256 ms
      to 8 ms. In Experiment 1, weak but significant correlations between TRAP and
      speech perception and phonological working memory were found, as well as a
      significantly lower TRAP performance by girls. Experiment 2 indicated a
      significant relation between TRAP and the phonological awareness task. The
      results give qualified support to the notion of a weak relationship between TRAP
      and speech perception and language skills among typical children. However, the
      gender differences in TRAP performance, the limited variance explained by the
      regression models, and the finding that only one of the language parameters
      correlated with TRAP do not support the notion of a causal relationship between
      language skills and TRAP. The possibility that TRAP is connected to general
      neurological maturation rather than specifically to language abilities is
      discussed.

PMID- 15503581
TI  - Self-report of ADHD symptoms in university students: cross-gender and cross
      national prevalence.
AB  - Little research has examined the structure and prevalence of attention
      deficit/hyperactivity disorder (ADHD) symptoms in university students, including
      whether symptom structure conforms to the bidimensional (i.e., inattention and
      hyperactivity-impulsivity) conceptualization of the Diagnostic and Statistical
      Manual of Mental Disorders (DSMV-IV; American Psychiatric Association, 1994) and
      whether self-reported symptoms vary across gender and country. A sample of 1,209
      university students from three countries (Italy, New Zealand, and the United
      States) completed a 24-item self-report measure (the Young Adult Rating Scale)
      tapping ADHD symptomatology. Factor analyses within the U.S. and New Zealand
      samples supported a bidimensional symptom structure, whereas weaker support for
      this conceptualization was provided by the Italian sample. Participants did not
      vary significantly by gender in symptom report; however, Italian students
      reported significantly more inattention and hyperactivity-impulsivity symptoms
      than students from the United States, and students from New Zealand reported more
      inattention symptoms than students from the United States. The prevalence of self
      reported ADHD symptoms beyond DSM-IV thresholds for diagnosis ranged from 0%
      (Italian women) to 8.1% (New Zealand men). The implications of these results for
      the use of DSM-IV criteria in identifying university students with ADHD are
      discussed.

PMID- 15503582
TI  - Visual-spatial strength in dyslexia: rapid discrimination of impossible figures.
AB  - It has often been conjectured that visual-spatial talents accompany dyslexia. But
      do individuals with dyslexia have unusual visual-spatial talents? Individuals
      with dyslexia were compared to controls on two computer-based visual-spatial
      tasks in two studies. In accordance with a diverging ability hypothesis, it was
      predicted that the dyslexia group would perform better on a global task,
      identifying impossible figures, and worse on a feature-oriented task, matching
      figures. These hypotheses were partially supported. On the global task, the
      dyslexia group was faster but no more accurate than the control group at
      identifying impossible objects. On the feature-oriented task, the control group
      outperformed the dyslexia group. The results indicate that the diverging ability
      hypothesis of dyslexia merits further investigation.

PMID- 15503583
TI  - [The optimal hematocrit--physiological observations].

PMID- 15503584
TI  - [The optimal hematocrit--and hemoglobin values in lung diseases].

PMID- 15503585
TI  - [Optimal hematocrit in encephalopathies].

PMID- 15503586
TI  - [The optimal hematocrit in heart diseases].

PMID- 15503587
TI  - [Heparin-induced type II thrombocytopenia in intensive care].

PMID- 15503588
TI  - Persistence of phonological processing deficits in college students with dyslexia
      who have age-appropriate reading skills.
AB  - This study investigated the phonological processing skills of university students
      with dyslexia. Fifty-nine students participated in this study: 28 with reading
      disabilities based on recent psychological assessments and a history of early and
      persistent reading problems; and 31 controls. The two groups did not differ on
      estimates of verbal and nonverbal abilities. The dyslexia group performed
      significantly less well on standardized measures of reading and spelling.
      However, the dyslexia group scores on these measures fell within the average
      range. The main dependent variables were subsumed under three areas of
      phonological processing: phonological awareness, phonological recoding in lexical
      access, and phonological recoding in working memory. The control group performed
      significantly better on all phonological processing measures, particularly those
      measures involving accuracy and response times. Despite age-appropriate
      performances on standardized reading and spelling measures, phonological
      processing deficits persisted in the dyslexia group. These findings support the
      causal role of phonological awareness in the acquisition of reading skills and
      indicate that differences in phonological processing skills are still evident in
      a sample of university students with dyslexia compared a group matched on age and
      education.

PMID- 15503589
TI  - Predicting delay in reading achievement in a highly transparent language.
AB  - A random sample of 91 preschool children was assessed prior to receiving formal
      reading instruction. Verbal and nonverbal measures were used as predictors for
      the time of instruction required to accurately decode pseudowords in the highly
      orthographically regular Finnish language. After 2 years, participants were
      divided into four groups depending on the duration of instruction they had
      required to reach 90 % accuracy in their reading of pseudowords. Participants
      were classified as precocious decoders (PD), who could read at school entry;
      early decoders (ED), who learned to read within the first 4 months of Grade 1;
      ordinary decoders (OD), who learned to read within 9 months; and late decoders
      (LD), who failed to reach the criterion after 18 months of reading instruction at
      Grade 2. Phonological awareness played a significant role only in differentiating
      PD from ED and OD. However, phonological awareness failed to predict the delayed
      learning process of LD. LD differed from all other groups in visual analogical
      reasoning in an analysis not containing phonological awareness measures. Letter
      knowledge and visual analogical reasoning explained above 90% of the PD-LD
      difference. Preschool composite (objects, colors, and digits) naming speed
      measures best predicted reading fluency at the end of Grade 2. The supportive
      role of orthographic knowledge in phonological awareness, the role of visual
      analogical reasoning, and the inability of phonological measures to discriminate
      late decoders are discussed.

PMID- 15503590
TI  - The development of reading speed in Italians with dyslexia: a longitudinal study.
AB  - The development of reading speed in Italian children with dyslexia was estimated
      using individualized growth curves for a group of 38 children with dyslexia
      tested longitudinally from the second to the eighth grade and compared with
      typical readers. Their reading speed development followed a linear trend of .3
      syllables per second per grade, approximately half the increment observed in
      typical children reading a passage and similar to typical children's reading of
      nonword lists. These findings give support to the deficit hypothesis versus the
      lag hypothesis and to reading speed as the core deficit in dyslexia with
      transparent orthographies.

PMID- 15503591
TI  - Does strategy knowledge influence working memory in children with mathematical
      disabilities?
AB  - This study investigated the relationship between working memory (WM), declarative
      strategy knowledge, and math achievement in children with and without
      mathematical disabilities (MD). Experiment 1 examined the relationship between
      strategy knowledge, verbal WM, and visual-spatial WM in children with MD as a
      function of initial, gain, and maintenance conditions. The results showed that
      after partialing the influence of reading, stable strategy choices rather than
      specific strategy knowledge was related to verbal and visual-spatial WM span in
      high demand (maintenance) conditions. Experiment 2 compared children with MD to a
      group of chronological age-matched children and a group of math ability-matched
      children on the same conditions as Experiment 1. Age-matched children's verbal
      and visual-spatial WM performance was superior to that of children with MD,
      whereas WM performance was statistically comparable between children with MD and
      younger children matched on math ability. The selection of expert strategies was
      related to high WM span scores in the initial conditions. After controlling for
      reading achievement in a regression analysis, verbal and visual-spatial WM,
      stable verbal strategy choices, and expert strategy choices related to visual
      spatial processing all contributed independent variance to math achievement.
      Overall, these results suggest that WM and math achievement are related to
      strategy knowledge.

PMID- 15503592
TI  - Metacognition and mathematical problem solving in grade 3.
AB  - This article presents an overview of two studies that examined the relationship
      between metacognition and mathematical problem solving in 165 children with
      average intelligence in Grade 3 in order to help teachers and therapists gain a
      better understanding of contributors to successful mathematical performance.
      Principal components analysis on metacognition revealed that three metacognitive
      components (global metacognition, off-line metacognition, and attribution to
      effort) explained 66% to 67% of the common variance. The findings from these
      studies support the use of the assessment of off-line metacognition (essentially
      prediction and evaluation) to differentiate between average and above-average
      mathematical problem solvers and between students with a severe or moderate
      specific mathematics learning disability.

PMID- 15503593
TI  - The effect of academic self-concept on ADHD and antisocial behaviors in early
      adolescence.
AB  - Using structural equation modeling techniques, we evaluated the effect of
      academic self-concept (ASC) on the development of attention-deficit/hyperactivity
      disorder (ADHD) and antisocial behaviors in early adolescence. Participants (n =
      445) were recruited from the Dunedin Multidisciplinary Health and Development
      Research study. Eligibility was determined by the presence of complete data for
      the following variables at the specified time periods: reading at age 7, teacher
      reports of ADHD and antisocial behaviors at age 7, self-ratings of ASC at ages 9
      and 11, and teacher reports of ADHD and antisocial behaviors at age 13. The
      results indicated that ASC is an important construct that directly contributes to
      the development of antisocial behaviors rather than to symptoms of ADHD. The
      results also indicated that children's early history of behavioral problems and
      academic performance contribute to the development of a more robust understanding
      of the impact of ASC on the development of disruptive behaviors in early
      adolescence.

PMID- 15503594
TI  - The validity and comparability of entrance examination scores after
      accommodations are made for students with LD.
AB  - Every year, thousands of college and university applicants with learning
      disabilities (LD) present scores from standardized examinations as part of the
      admissions process for postsecondary education. Many of these scores are from
      tests administered with nonstandard procedures due to the examinees' learning
      disabilities. Using a sample of college students with LD and a control sample,
      this study investigated the criterion validity and comparability of scores on the
      Miller Analogies Test when accommodations for the examinees with LD were in
      place. Scores for examinees with LD from test administrations with accommodations
      were similar to those of examinees without LD on standard administrations, but
      less well associated with grade point averages. The results of this study provide
      evidence that although scores for examinees with LD from nonstandard test
      administrations are comparable to scores for examinees without LD, they have less
      criterion validity and are less meaningful for their intended purpose.

PMID- 15503595
TI  - Perceptions and knowledge of preservice and inservice teachers about early
      literacy instruction.
AB  - A major conclusion from the last decade of research on children with poor reading
      performance is that early, systematic instruction in phonological awareness and
      letter-sound correspondences improves early reading and spelling skills and
      results in a reduction of the number of students who are reading below grade
      level. To teach reading to at-risk students and students with learning
      disabilities, teachers need to have positive perceptions regarding the role of
      systematic, explicit instruction, as well as knowledge of English language
      structure. The purpose of this study was to examine the perceptions and knowledge
      of general educators at two professional levels toward early literacy instruction
      for students at risk for reading failure. Unfortunately, our findings are similar
      to those obtained by Moats in 1994: Many general education teachers, at both
      preservice and inservice levels, are not prepared adequately for this challenging
      task.

PMID- 15503596
TI  - People protected--public health prepared through a competent workforce.

PMID- 15503598
TI  - Public health response to bioterrorism with Bacillus anthracis: coordinating
      public health laboratory, communication, and law enforcement.
AB  - In October 2001, public health departments across the United States were part of
      an intensive response to a bioterrorism event using anthrax spores delivered by
      mail. It is useful to examine this experience as an unscripted exercise of
      bioterrorism response capacity, more realistic than scenarios of planned
      exercises. The event particularly challenged public health laboratory and
      communications capacity, but it also tested surveillance and training capacity.
      The bioterrorism response demonstrated the importance of strong partnerships
      between the public health laboratory and emergency response agencies as well as
      medical providers and the usefulness of open, flexible communication strategies.

PMID- 15503597
TI  - Local and state collaboration for effective preparedness planning.
AB  - State and local collaboration is critical to effective preparedness and response
      planning. Through various assessments, the National Association of County and
      City Health Officials (NACCHO) is tracking the way in which local and state
      public health agencies are coordinating their planning efforts to ensure adequate
      bioterrorism and emergency response capacities. NACCHO's analysis of planning
      provides a case study of effective and ineffective collaboration. NACCHO intends
      to share these lessons to provide local and state public health agencies with
      strategies for enhancing collaboration in the future.

PMID- 15503599
TI  - Persistence of a mock bio-agent in cross-contaminated mail and mailboxes.
AB  - Among the 22 confirmed or suspected cases of anthrax during the bioterrorism
      incidents in 2001, all but two seemed traceable to spores from threat letters.
      Although no anthrax spores were found in the environments frequented by two
      females who died of the disease, a suspicion persists that the deaths were
      somehow related to the mail. This study assesses the spread and persistence of a
      mock biological agent from a source-letter to other mail and to a receiving
      mailbox. Successive placement and removal of letters were found to reduce the
      number of residual bio-agent particles in a mailbox. This suggests that a
      sweeping action is taking place that can affect the quantity of bio-agent
      remaining. The exercise supports the possibility that the two females were
      exposed to spores on mail that had been in their mailboxes although no trace of
      spores could later be found in their boxes.

PMID- 15503600
TI  - Enhancing nuclear emergency preparedness: Vermont's distribution program for
      potassium iodide.
AB  - On January 31, 2002, Vermont's health commissioner requested potassium iodide
      (KI) for individuals in the 10-mile Emergency Planning Zone of the nuclear power
      facility. Vermont's KI distribution program emphasized public information about
      the role, risks, and benefits of KI. Predistribution ensured that individuals
      could receive KI in a 0- to 4-hour time period, to provide maximum protection.
      Five months after the program began, more than 1,000 individuals had received KI,
      and 3,000-4,000 KI doses have been distributed in schools. Efforts are ongoing to
      identify barriers to participation, provide public education, and evaluate KI
      distribution efforts.

PMID- 15503601
TI  - Evaluation of the Washington State National Pharmaceutical Stockpile dispensing
      exercise: Part I--Patient volunteer findings.
AB  - The Centers for Disease Control and Prevention's National Pharmaceutical
      Stockpile (NPS) program is designed to ensure the availability of life-saving
      antibiotics, other medical supplies, and equipment and their prompt delivery to
      the site of a disaster, including a possible bioterrorist incident, anywhere in
      the United States. On January 24, 2002, the Washington State Department of Health
      conducted an exercise, simulating a mass exposure to Bacillis anthracis, to test
      the NPS dispensing portion of the Washington State plan. This drill included the
      recruitment, education, and postexposure prophylaxis of over 230 volunteer
      patients. This article describes and discusses findings from an exit survey
      completed by these patient volunteers.

PMID- 15503602
TI  - Turning point sets the stage for emergency preparedness planning.
AB  - Nearly a billion dollars were made available to state health departments through
      federal grants in the spring of 2002 for public health emergency preparedness
      plans. Twenty-one states had already been participating for some years in The
      Robert Wood Johnson Foundation's Turning Point Initiative. This article
      illustrates how earlier practice and experience in developing cross-sector
      collaborations and institutionalizing a model of broad-based partnerships for
      public health decision making can increase effectiveness and efficiency in
      responding to a call for action around an emergency.

PMID- 15503603
TI  - Local collaborations: development and implementation of Boston's bioterrorism
      surveillance system.
AB  - The Boston Public Health Commission developed and implemented an active
      surveillance system for bioterrorism and other infectious disease emergencies. A
      bioterrorism Surveillance Task Force was formed with representatives from local
      emergency medicine, infection control, infectious diseases, public health, and
      emergency medical services. These local agencies worked together to develop a
      reliable, easy to use electronic surveillance system. Collaboration at the local
      level and building on existing relationships is a key component of this system.
      Effective follow-up systems and technology back-up plans are essential. Improved
      communication networks and increased bioterrorism education for clinicians and
      the general public have also been achieved.

PMID- 15503604
TI  - Regional emergency preparedness efforts by local health departments in Western
      New York.
AB  - Public health agencies at all levels are now under increasing pressure to prepare
      for and respond to emerging natural and manmade threats to the health and
      wellness of those they serve. In particular, local health departments must be
      prepared to provide front-line defense and first response as threats of terrorism
      have become increasingly real. Success in meeting this monumental task will be
      highly dependent on funding as well as the availability of other resources.
      Although local health departments serving smaller counties may have fewer
      resources and receive less preparedness funding, they must still develop similar
      plans, surveillance systems, and response capabilities as local health
      departments serving larger counties (albeit on a smaller scale). Although local
      health departments serving larger counties may have more resources and receive
      more preparedness funding, they may face a greater chance of an intentional
      terrorist act and could benefit from support from local health departments
      serving smaller counties. Regional planning and response solutions to this
      challenge will allow partnerships of small and large local health departments to
      pool their resources and cooperatively provide more services with less
      duplication using whatever funding is available. This article describes that
      process as it is occurring in western New York among eight local county health
      departments.

PMID- 15503605
TI  - Electronic patient registration and tracking at mass vaccination clinics: a
      clinical study.
AB  - To protect the citizens of the United States from the use of dangerous biological
      agents, the Center for Disease Control and Prevention (CDC) has been actively
      preparing to deal with the consequences of such an attack. Their plans include
      the deployment of mass immunization clinics to handle postevent vaccinations. As
      part of the planning efforts by the Western New York Public Health Alliance, a
      Web-based electronic patient registration and tracking system was developed and
      tested at a recent trial smallpox vaccination clinic. Initial goals were to
      determine what the pitfalls and benefits of using such a system might be in
      comparison to other methods of data collection. This exercise proved that use of
      an electronic system capable of scanning two-dimensional bar codes was superior
      to both paper-based and optical character recognition (OCR) methods of data
      collection and management. Major improvements in speed and/or accuracy were
      evident in all areas of the clinic, especially in patient registration, vaccine
      tracking and postclinic data analysis.

PMID- 15503606
TI  - Legal implications of the Smallpox Vaccination Program.
AB  - President George W. Bush's Smallpox Immunization Program will expose health care
      workers and public health agencies to liability for negligent administration of
      the vaccine. Section 304 of the Homeland Security Act, supplemented by Secretary
      Thompson's Emergency Declaration, shifts liability to the federal government.
      State indemnification laws and workers' compensation laws protect some potential
      defendants. The Smallpox Personnel Protection Act of 2003 provided a new source
      of compensation to injured health care workers. This article examines the scope
      of protection offered by these laws.

PMID- 15503607
TI  - Developing the academic institution's role in response to bioterrorism: the Iowa
      Center for Public Health Preparedness.
AB  - The terrorist acts during the fall of 2001 triggered renewed concern about the
      capacity of the nation's public health system to deal with crisis. A critical
      element of the response ability of the public health system is a prepared
      workforce. Based on a pre-existing concern about emerging infectious disease, the
      Centers for Disease Control (CDC), working with the Association of Schools of
      Public Health, had established a network of university-based Centers for Public
      Health Preparedness. The events of September 11 accelerated, expanded, and
      focused this effort. This article discusses this national program, details the
      activities of the based Center for Public Health Preparedness located at the
      University of Iowa, and suggests preparedness issues deserving future
      development.

PMID- 15503608
TI  - Building academic-practice partnerships: the Center for Public Health
      Preparedness at the Columbia University Mailman School of Public Health, before
      and after 9/11.
AB  - The Center for Public Health Preparedness at the Columbia University Mailman
      School of Public Health is part of a national network of academic centers
      established by the Centers for Disease Control and Prevention to strengthen links
      between public health practice and academe, especially for public health
      workforce development. Since its inception in Fall 2000, the Center has been
      working in partnership with the New York City Department of Health & Mental
      Hygiene (DOHMH) on planning and competency-based training in emergency
      preparedness (including bioterrorism and infectious diseases) and evaluation.
      Initial programs with DOHMH included development of a 3-hour orientation to basic
      emergency preparedness for their workforce. In the wake of 9/11 and the anthrax
      events, Center members gave over two dozen presentations at community forums,
      seminars, and clinical rounds, and over 100 press interviews, provided lay
      language information through community forum presentations and the School's Web
      site, and developed a database of volunteers for surge capacity. Subsequent
      programs include bioterrorism response training for clinicians and emergency
      medical services personnel, incident command for public health, and a study of
      evacuation from the World Trade Center on 9/11.

PMID- 15503609
TI  - Academic health centers and the war on terrorism.

PMID- 15503610
TI  - Maribor General Hospital through time.

PMID- 15503611
TI  - Maribor General Hospital as a teaching hospital.

PMID- 15503612
TI  - The value of adjunctive vein patches to improve the outcome of femorodistal
      polytetrafluoroethylene bypass grafts.
AB  - PURPOSE: A non-randomised comparative study was carried out to determine whether
      an interposition vein patch improves the long-term outcome of infrapopliteal and
      distal PTFE bypass grafts. PATIENTS AND METHODS: A prospective study (1992-1999)
      was carried out between 2 groups of patients. The first group comprised 86
      patients undergoing the same number of femoropopliteal or infrapopliteal bypass
      procedures between March 1992 and February 1999 at our institution. PTFE with
      modified interposition vein patch was used as bypass graft. The second group
      comprised 191 patients who received 216 autogenous vein bypass grafts in the same
      period. The third group consisted of 94 patients from a retrospective study
      between 1985-1992, in whom PTFE bypass procedures without interposition vein
      patches had been performed. The indication for surgery was critical lower limb
      ischemia in all groups. Primary, secondary and limb salvage rates were calculated
      using the life-table method. The life tables were compared with the log-rank
      test. RESULTS: Five-year primary, secondary and limb salvage rates for PTFE with
      interposition vein patches were 53.4%, 60.7% and 68% for below-knee popliteal,
      and 29.5%, 35.5% and 41% for infrapopliteal bypass grafts, respectively. Five
      year primary, secondary and limb salvage rates for autogenous vein grafts were
      78.9%, 82.3% and 84.2% for below-knee popliteal, and 51%, 54.7% and 75% for
      infrapopliteal bypass grafts, respectively. Five-year primary, secondary and limb
      salvage rates for PTFE grafts without interposition vein patches were 29.7%,
      37.8% and 43.6% for below-knee popliteal, and 6.9%, 9.2% and 14.7% for
      infrapopliteal bypass grafts, respectively. Statistical analysis showed a
      significant difference in primary, secondary and limb salvage rates between the
      groups. CONCLUSION: The results of our study indicate that autogenous vein still
      remains the graft of choice for below-knee and infrapopliteal bypass
      reconstruction. Their long-term patency and limb salvage rates were significantly
      better compared with PTFE grafts, with or without interposition vein patches.
      When adequate autogenous vein is not available, the interposition of a vein patch
      considerably improves the long-term outcome of PTFE bypass grafts.

PMID- 15503613
TI  - A prospective study of the correlation between Chlamydia trachomatis infection
      and secondary bleeding following large loop excision of the transformation zone
      (LLETZ).
AB  - To determine the effect of Chlamydia trachomatis (CT) on the occurrence of
      secondary bleeding following large loop excision of the transformation zone
      (LLETZ), 103 patients with cervical intraepithelial neoplasia (CIN) were included
      in this study. In order to determine the presence of CT infection, cytological
      material for direct immunofluorescence analysis was obtained prior to LLETZ.
      After surgery, the patients were followed up for postoperative bleeding. Groups
      with and without postoperative bleeding were compared as regards the frequency of
      CT infection. Of 103 patients, 8 (7.8%) were CT positive and 95 (92.2%) were CT
      negative. Postoperative bleeding only occurred in 6 (2.8%) patients, all of whom
      were CT negative. Thus, in CT-positive patients, no secondary bleeding occurred.
      CT infection of the uterine cervix in patients with CIN is rare and does not
      appear to be important for the occurrence of postoperative bleeding after LLETZ.

PMID- 15503614
TI  - Role of arteriovenous shunting in venous ulcers--therapeutic implications.
AB  - Although the presence of arteriovenous communications in patients with chronic
      venous ulcers has been confirmed in several studies, their role in the
      pathogenesis of venous ulcers is still uncertain. They possibly do play an
      important role in the aetiology of chronic venous insufficiency. There is also
      substantial evidence to suggest that arteriovenous communications develop as a
      result of chronic venous hypertension. The question raised in this pilot study
      was whether the importance of arteriovenous shunts in the genesis of venous ulcer
      disease is such that their obliteration might lead to long-term healing. This
      clinical study was also designed to determine whether therapeutic
      microembolization of nutritive arterial branches to arteriovenous fistulas, found
      in patients with venous ulcers, facilitates healing of venous ulcers resistant to
      previous conservative and/or classical surgical treatment. From 1997 to 1999, 34
      patients (22 women and 14 men, mean age 51.3 years) with chronic venous ulcer
      resistant to classical treatment were included in the study. Arteriovenous
      shunting was demonstrated by digital subtraction angiography in 31 patients
      (31/34 = 91%). The embolization procedure of muscular arterial branches feeding
      the arteriovenous shunts with microspirals and microparticles led to ulcer
      healing in 13 patients (13/31). The results suggest that the role of
      arteriovenous shunting in chronic venous ulceration resistant to classical
      treatment is more important than previously suggested, and that their
      microembolization might lead to complete healing.

PMID- 15503615
TI  - Video-assisted thoracic surgery--a new possibility for the management of
      traumatic hemothorax.
AB  - Thoracic trauma usually results in severe injury and is associated with a high
      rate of mortality, either due to the trauma itself or due to trauma-related
      causes. Early diagnosis and treatment of chest injuries is a very important
      determinant of the outcome. Video-assisted thoracic surgery (VATS) is gaining
      increasing importance as a diagnostic and therapeutic procedure. Especially in
      cases of traumatic hemothorax, this new method is very advantageous because of
      its simplicity, safety and efficacy in the acute phase of haemorrhage, after
      stabilisation of the patient, as well as in the treatment of complications.

PMID- 15503616
TI  - Dependence of the in-vitro fertilization capacity of the oocyte on perifollicular
      flow in the preovulatory period of unstimulated cycles.
AB  - BACKGROUND: One method to economize on monitoring cycles for IVF and improving
      its outcome is follicular selection. The purpose of our study was to determine
      whether quantitative indices of perifollicular blood flow allow the prediction
      which follicles contain a fertilizable oocyte and which do not. METHODS: This
      prospective study included 178 unstimulated cycles for IVF in patients treated
      for tubal infertility, endometriosis and unknown causes of infertility that ended
      with follicular aspiration. All male partners had a normal spermiogram. Cycles
      were monitored using ultrasound folliculometry and estimation of serum estradiol
      concentrations. On the day of hCG administration (day 0), day +1 and prior to
      follicular aspiration (day +2), perifollicular blood flow was measured using
      color and pulsed Doppler. The pulsatility index (PI), resistance index (RI) and
      peak systolic velocity (PSV) between the group in which fertilization occurred
      (group A) and that in which no fertilization occurred (group B) were compared.
      Student's t-test and ANOVA were used for statistical analysis. RESULTS: The
      oocyte recovery rate was 71.5% and the fertilization rate 74.8%. Comparison of RI
      and PI between group A (N = 95) and group B (N = 32) revealed a decline in PI and
      RI after hCG administration in both groups. Only on day 0 was PI in group A
      significantly lower than that in group B. The difference in RI and PSV between
      the two groups was not statistically significant. ANOVA showed that there was no
      significant difference in serial Doppler measurements between the two groups.
      CONCLUSION: We confirmed an increased perifollicular blood flow in the
      preovulatory period. Quantitative indices of perifollicular blood flow are of
      limited value as parameters for cycle monitoring and decision-making in
      unstimulated cycles for IVF.

PMID- 15503617
TI  - Ultrasonographic assessment of celiac disease in children: comparison with
      antiendomysium antibodies and histology.
AB  - Several attempts have been made to identify accurate screening tests for celiac
      disease (CD) with the aim to reduce the need for biopsy or obtaining appropriate
      selection criteria prior to intestinal biopsy. In this context we evaluated the
      usefulness of screening for endomysial antibodies (EMA) in the diagnosis of CD in
      children in comparison with CD-related changes detected by ultrasound (US) or
      biopsy. PATIENTS: We studied 35 children (1-15 years, 22 girls and 13 boys, mean
      age 8 years) with untreated CD (N = 15), treated CD (N = 10) and controls (N =
      10), undergoing small bowel biopsy as a diagnostic procedure. METHODS: US of the
      small bowel was performed prior to mucosa biopsy using a 4- or 7-MHz transducer
      of a computed sonography device. The thickness of the intestinal wall and small
      bowel motility were recorded. Simultaneously, all children had serum routinely
      sampled for IgA EMA. RESULTS: All controls had histologically normal small bowel
      mucosa, US showed a small bowel wall thickness of 1 mm with normal motility in 9
      children and non-specific wall changes in 1 child. EMA was weakly positive in 1
      of these, and negative in all other controls. Of 15 children with untreated CD,
      severe enteropathy and strongly positive EMA were found in 10 cases; in 5
      children moderate enteropathy and positive EMA were detected. Severe US changes
      were found in all of these children (1.6 mm thickness of the intestinal wall,
      hyperperistalsis and abundant fluid in the bowel). Mild enteropathy was found in
      10 children with treated CD (3 months of a gluten-free diet). EMA was positive in
      2 children and weakly positive in 8. Non-specific US changes were found in 6
      children. In conclusion, our results indicate that US provides valuable
      information on small-bowel wall structure and can help in decision making on the
      necessity of small bowel biopsy. The present study confirms a stronger
      correlation between EMA and CD than between US and CD.

PMID- 15503618
TI  - Serum carcinoembryonic antigen levels in patients operated for colorectal
      carcinoma.
AB  - BACKGROUND: The only method of treatment that offers a favourable prognosis for
      colorectal carcinoma is radical resection of a part of the colon or rectum
      including the pertinent lymph glands and radical removal of metastases. However,
      even such presumably curative surgery does not ensure full recovery, as
      recurrences are frequent and, according to several analyses, the 5-year survival
      rate is less than 50%. The most significant reason for this poor therapeutic
      success are residual micrometastases. Therefore, additional treatment strategies
      are attempted in several patients. Various prognostic factors of disease
      recurrence are known. One such prognostic sign is the serum carcinoembryonic
      antigen (CEA) level measured shortly after surgery. PATIENTS AND METHODS: All
      patients operated on electively for colorectal carcinoma at our institution
      within one year were followed. According to preoperative serum CEA levels, the
      patients were divided into a study group (preoperative CEA more than 10 ng/mL)
      and controls (preoperative CEA less than 10 ng/mL). In the former category,
      patients who underwent radical R0 resection were divided into three groups
      according to their postoperative serum CEA levels and CEA half-life: (CEA) R0-,
      (CEA) R1- and (CEA) R2-resected patients. All patients were then followed for 24
      months; the number of recurrences and survival rates were registered. RESULTS: A
      statistically significant difference in regard of survival and the number of
      recurrences was noted in patients divided according to the stage of disease,
      particularly between the three groups of patients from the study group undergoing
      curative surgery. After two years, survival was 96.97% in the CEA R0 group,
      66.66% in the (CEA) R1 group and 50% in the (CEA) R2 group. Recurrences were as
      follows; 3.03% in (CEA) R0, 83.3% in (CEA) R1 and 100% in (CEA) R2. CONCLUSIONS:
      The results of our study confirm the prognostic value of serum CEA measurement,
      in particular its half-life, following surgery for colorectal carcinoma.

PMID- 15503619
TI  - [Argon plasma coagulation (APC): a new mode in gastrointestinal endoscopy--first
      experience].
AB  - Argon plasma coagulation (APC) is a new method of non-contact electrocoagulation
      in which current is applied to tissues by means of ionised argon gas (argon
      plasma). The development of special applicators has made this method applicable
      for gastrointestinal endoscopy. The primary indication for APC is the treatment
      of hemorrhage in the gastrointestinal tract. APC has been proven to be highly
      effective and easily used, with clear advantages over previously used methods.
      This article describes the introduction of APC in Slovenia and the first
      experiences with this method in the clinical department of internal medicine in
      Maribor.

PMID- 15503620
TI  - [Simple renal cysts and hypertension].
AB  - BACKGROUND: Simple renal cysts are frequent findings in mid-aged people, their
      frequency increases with age. They are often detected by abdominal ultrasound
      and/or computed tomography during diagnostic procedures. Hypertension is also a
      frequent disease and its prevalence increases with age as well. The aim of our
      study was to evaluate the association between simple renal cysts and hypertension
      in a group of patients with normal renal function. PATIENTS AND METHODS: Ninety
      one patients (58 female and 33 male; mean age 50.5 +/- 16.9 years) were included
      in the study, all with normal renal function (serum creatinine <100 micromol/l).
      The patients were examined with a real-time ultrasound device with a 2-4 MHz
      convex transducer. Kidney size, presence, number and diameter of cysts were
      examined and the presence of hypertension was determined. The presence of
      hypertension was defined by the administration of antihypertensive agents,
      systolic blood pressure greater than 140 mmHg and/or diastolic blood pressure
      greater than 90 mmHg. RESULTS: Simple renal cysts were found in 19 (20.88%)
      patients. Only cortical cysts were found in 11 (12.09%) patients, only
      parapelvinic cysts were found in 4 (4.39%) patients. Four (4.39%) patients had
      cortical and parapelvinic cysts. Cortical cysts in both kidneys were found in
      five (5.49%) patients, parapelvinic cysts in both kidneys were found in three
      (3.29%) patients. Bilateral renal cysts were present in 10 (10.99%) patients, six
      (60%) of them had hypertension. We found no difference in the presence of simple
      renal cysts according to sex. Hypertension was detected in 30 (32.97%) patients.
      Hypertension was significantly more frequent in patients with simple renal cysts
      (P < 0.041) than in with patients without cysts. Simple renal cysts were also
      significantly associated with age (P < 0.01). With multiple regression analysis
      we found a significant association with age only (P < 0.0001), but not with
      hypertension (P = 0.394). CONCLUSIONS: Simple renal cysts are frequent findings
      and their incidence increases with age. We found an association between simple
      renal cysts and hypertension. However, with multiple regression analysis only an
      association between simple renal cysts and age could be detected.

PMID- 15503621
TI  - [Bone healing and biochemical blood parameters after arteficial osteotomy of
      rabbits' femur treated by low-frequency magnetic field].
AB  - Aim of the study was to investigate the effect of magnetic fields on bone
      fracture healing and biochemical indices of bone turnover. Young male "White
      Newzealand Rabbits" were exposed after osteotomy of the femur of the hind-paw in
      narcosis for 31 days in a low-frequency magnetic field (field parameters:
      frequency 15.3 Hz, signal form: sine, magnetic field strength: 50 microT peak
      value). Eight animals each were assigned randomly for a single blind study to 3
      groups. Controls were kept in a sham-exposition cage without magnetic field
      influence and were compared with a group in (Pseudo-) Helmholtz-coil arrangement
      with a horizontal magnetic field and a further group in a cylinder coil (vertical
      magnetic field). The daily duration of stay in the (sham-) exposition
      arrangements amounted to 30 minutes respectively. The activities of the alkaline
      phosphatase (AP) and creatinkinase (CK) were evaluated preoperatively, after the
      19th and 31st experimental day, the callus density by means of computertomography
      after the 31st experimental day (two-tailed t-test). The densitometrically
      assessed callus densities of the magnetically treated groups were highly
      significant (p < 0.0001) compared with the controls. In spite of accelerated
      fracture healing the activities of the ALP were lower at both postoperative
      examinations than preoperatively, in the cylinder-coil the activity proved to be
      significantly lower (p < 0.05) compared with the controls after 31 days.
      Significant differences in CK were detected at no time. In conclusion, we confirm
      the positive magnetic field effects on fracture healing. The mechanisms of
      interaction of magnetic field and bone fracture healing remain to be clarified.

PMID- 15503622
TI  - Measurement of the lateral recess angle as a possible alternative for evaluation
      of the lateral recess stenosis on a CT scan.
AB  - Stenosis of the lateral recess in the lumbar spinal canal is a clinical problem,
      especially in terms of surgical management. Criteria for the diagnosis and
      surgical treatment of lateral recess stenosis (LRS) are not clearly defined.
      Several authors have suggested measurement of the lateral recess height (LRH) on
      computed tomography (CT) scans as a helpful tool for making decisions in regard
      of management. The present study is based on the assumption that measurement of
      the lateral recess angle (LRA) may be useful in the clinical management of
      lateral recess stenosis. The reliability and significance of the results have
      been analyzed. In 35 patients, the stenosis was confirmed by intraoperative
      measurement of the lateral recess height. Fifty-three affected lateral recesses
      were analyzed. Before surgery, the heights on CT scans were measured. The mean
      value was 3.3 mm (SD = 0.9 mm), while 41 of them were 3.6 mm or less.
      Furthermore, the angles on CT scans were evaluated. The mean value was 25.9
      degrees (SD = 4.9 degrees), 48 of them were 30 degrees or less and only 5 of them
      achieved more than 30 degrees. Results reveal that the best quantitative
      determination of a lateral recess stenosis is a CT scan angle measurement with a
      critical value of 30 degrees. A CT scan height of 3.6 mm or less is also
      indicative of stenosis. Statistical evaluation of the data by multiple regression
      analysis revealed agreement between intraoperative findings and measured heights
      (p = 0.02), while even better results were noted for angles (p < 0.01).
      Interfacet distance (IF) was found to be least predictive (p = 0.04).

PMID- 15503623
TI  - Familial hypomagnesemia--hypercalciuria and pseudotumor cerebri.
AB  - Approximately 30 patients with familial hypomagnesemia-hypercalciuria have been
      reported. We describe an 8-year-old girl with cardinal findings of familial
      hypomagnesemia-hypercalciuria (hypomagnesemia, hypermagnesiuria, hypercalciuria,
      renal insufficiency, hyperuricemia, elevated serum parathormone, hyposthenuria
      and nephrocalcinosis), who received combination therapy consisting of magnesium
      salts, thiazide diuretic and potassium supplementation. At the 4-year follow-up
      investigation under this treatment, the patient was found to have cerebral
      pseudotumor (increased intracranial pressure with normal or small ventricles on
      neuroimaging, no evidence of an intracranial mass and normal cerebrospinal fluid
      composition) with papilledema and visual field defects. Thiazide therapy was
      terminated and the cerebral pseudotumor disappeared. The authors hypothesize that
      cerebral pseudotumor in this patient was related to severe hypocalcemia, as a
      consequence of profound hypomagnesemia induced by protracted thiazide treatment.
      To our knowledge, this is the first report of a child with familial
      hypomagnesemia-hypercalciuria who developed pseudotumor cerebri after thiazide
      therapy.

PMID- 15503624
TI  - Bilateral eye injury caused by a high-pressure water jet from a fire hose.
AB  - We present a case of bilateral eye injury caused by a high-pressure water jet
      from a fire hose. Eye injury secondary to high-pressure water jets are relatively
      rare, but invariably result in severe damage to all ocular structures. A 51-year
      old woman was admitted to our ophthalmologic department for treatment following a
      direct hit in the face by a water jet from a fire hose from a distance of about
      one meter. The patient had bilateral extensive eyelid edema and ecchymosis,
      conjunctival chemosis with hemorrhage, vitreous hemorrhages in the right eye and
      iridodialysis with hyphema in the left eye, a transient decrease in intraocular
      pressure, bilateral superior commotio retinae with macular edema, and bilateral
      impairment of vision. The patient was treated with topical corticosteroids. Four
      months later she was re-admitted to our department for surgical repair of
      iridodialysis in the left eye. Iridodialysis had affected the entire superior
      nasal portion of the iris, and the pupil was displaced downward temporally. The
      iris partly obscured the visual axis. After surgical repair the visual axis was
      free. At a follow-up examination two years later, the ocular findings were the
      same. The best corrected visual acuity was 0.1 in the right eye and 0.3 in the
      left eye. Visual impairment was a consequence of permanent posttraumatic
      posterior fundus changes, particularly of the macula in both eyes. Intraocular
      pressure was within normal limits in both eyes. Injuries caused by high-pressure
      water jets are usually bilateral. The injuries are mainly confined to the lower
      anterior portions of the eye (Bell's phenomenon). Our patient had bent forward
      during the accident, therefore the central and upper chorioretinal portions were
      also affected. Such injuries usually cause severe damage to the anterior and
      posterior portions of the eyes and greatly reduce visual acuity in both eyes.
      Because of the risk of late complications (cataract, glaucoma, retinal
      detachment), long-term follow-up is recommended in such patients.

PMID- 15503625
TI  - Epicardial electrode insertion by means of video-assisted thoracic surgery
      technique.
AB  - BACKGROUND: The number of patients who depend on pacemaker (PM) insertion is
      steadily increasing. Slovenia has two centers for PM insertion, in which 250 such
      procedures are performed every year. Thus, with regard to the number of
      procedures per year per million inhabitants, Slovenia holds a middle position in
      the list of countries. METHOD: We report a patient with cardiomyopathy, complete
      A-V block (A-V block III) and permanent transvenous pacing lead replacements. The
      resulting thrombosis of the superior vena cava compelled us to insert an
      epicardial permanent pacing lead. Video-assisted thoracic surgery (VATS)
      technique was selected. RESULTS: Surgery was safe for the patient, of 40 minutes'
      duration, and with minimum blood loss. The postoperative course was devoid of
      complications, the patient's circulation was stable, and he was able to leave the
      hospital one week later. CONCLUSIONS: We believe that the choice of the
      thoracoscopic method of epicardial permanent pacing lead insertion is
      appropriate, and that the method is safe and promising as it broadens the
      indications for the VATS technique.

PMID- 15503626
TI  - Long-term survival following treatment of multiple supra- and infratentorial
      aspergillus brain abscesses.
AB  - Aspergillus brain abscess is a rare but frequently fatal disease. Despite the
      scarcity of reported survivors, a combination of medication and surgical
      treatment might be effective. We report a 37-year-old man who developed multiple
      aspergillus brain abscesses after severe bacterial pneumonia. The following
      strategy was used to treat the patient: diagnostic puncture of one of the
      abscesses, long-term treatment with medication, excision of chronic granuloma in
      the occipital lobe and fourth ventricle, surgical treatment of the hydrocephalus.
      Following various surgical and antifungal treatments, the patient survived.
      Nearly three years after discharge, he still is in good physical condition and
      has a moderate neurologic deficit. Only 36 patients have been reported to have
      survived longer than three months after receiving treatment for brain
      aspergillosis. A course of medication in combination with various surgical
      procedures was required to achieve a successful outcome in this otherwise fatal
      disease.

PMID- 15503627
TI  - Preparation of reversibly glucose-responsive hydrogels by covalent immobilization
      of lectin in polymer networks having pendant glucose.
AB  - Glucose-responsive hydrogels were prepared by copolymerization of a monomer
      having a pendant glucose with modified lectin (concanavalin A (ConA)) having
      vinyl groups. Swelling behavior of ConA-copolymerized glucosyloxyethyl
      methacrylate (GEMA) hydrogels was discussed from the viewpoint of their synthetic
      condition and structures. The swelling ratio of the ConA-copolymerized GEMA
      hydrogels was strongly dependent on the glucose concentration in a buffer
      solution. As free glucose resulted in the dissociation of the complex between
      ConA and pendant glucose in the networks and the cross-linking density in the
      hydrogel decreased, the hydrogels swelled gradually in the presence of free
      glucose. Leak of ConA from the ConA-entrapment hydrogel and ConA-copolymerized
      hydrogel was examined in order to discuss the reversible changes of their glucose
      responsive behavior. During swelling in the presence of free glucose, ConA leaked
      out of the ConA-entrapment GEMA hydrogel but did not out of the ConA
      copolymerized GEMA hydrogel. As a result, the ConA-copolymerized GEMA hydrogel
      showed the reversible swelling changes in response to a stepwise change in the
      glucose concentration. This study revealed that covalent immobilization of ConA
      in the GEMA networks is very important for development of reversibly glucose
      responsive hydrogels.

PMID- 15503628
TI  - Preparation of cationic comb-type copolymer having guanidino moieties and its
      interaction with DNAs.
AB  - In order to evaluatet effects of different cationic moieties, such as primary
      amino and guanidino groups, on interactions between DNAs and cationic comb-type
      copolymers, comb-type copolymers having guanidino groups were prepared. The
      copolymers (GPLL-g-Dex) were obtained by guanidination of poly(L-lysine)-graft
      dextran copolymers (PLL-g-Dex) using 1-guanyl-3,5-dimethylpyrazole nitrate under
      weak basic conditions. The resulting copolymers were characterized using NMR
      spectroscopy and size-exclusion chromatography-multiangle light scattering (SEC
      MALS). The primary amino groups of the PLL backbones were thoroughly replaced
      with guanidino ones without any detectable side reactions, including
      fragmentation of PLL or Dex chains. The interactions of GPLL-g-Dex and PLL-g-Dex
      with DNAs were assessed by UV-melting curve measurements. These copolymers
      diversly affected the melting behavior of double-stranded DNA (dsDNA). GPLL-g-Dex
      has a lower ability to increase the Tm of dsDNA than PLL-g-Dex and also exhibits
      a higher affinity for dsDNA. The results suggest that the stability of dsDNA may
      be affected not only by ionic interaction between the copolymers and DNAs, but
      also by other modes of interactions, such as hydrogen-bondinginteractions.

PMID- 15503629
TI  - Anti-inflammatory drug delivery from hyaluronic acid hydrogels.
AB  - Two different types of hyaluronic acid (HA) hydrogels were synthesized by
      crosslinking HA with divinyl sulfone (DVS) and poly(ethylene glycol)-divinyl
      sulfone (VS-PEG-VS). Vitamin E succinate (VES), an anti-inflammatory drug, and
      bovine serum albumin (BSA), a model of anti-inflammatory protein drugs, were
      loaded into the gels and their release kinetics were measured in vitro. VES and
      BSA released with a burst from both HA hydrogels during the first few hours, and
      release continued gradually for several days. The rate of release from HA-VS-PEG
      VS-HA hydrogels was faster than that from HA-DVS-HA hydrogels, presumably due to
      the lower crosslink density in the former. The anti-inflammatory action of
      released VES was tested by incubating peripheral blood mononuclear cells (PBMC)
      on HA hydrogels with and without VES in the gel. The number of cells adhering on
      HA hydrogels was very low compared to that on tissue culture polystyrene (TCPS),
      which might be one of the important advantages of using HA hydrogels for implant
      coatings or tissue engineering applications. ELISA test results showed that the
      tumor necrosis factor-alpha (TNF-alpha) concentration was very low in the
      supernatant of the wells containing the HA hydrogel with VES in contact with the
      activated macrophages compared to that without VES. This is probably the effect
      of the released VES reducing the production of anti-inflammatory cytokine, TNF
      alpha. HA hydrogels containing anti-inflammatory drugs may have potential for use
      in tissue engineering and also as biocompatible coatings of implants.

PMID- 15503630
TI  - Plasma protein adsorption to surfaces grafted with dense homopolymer and
      copolymer brushes containing poly(N-isopropylacrylamide).
AB  - Growing polymer chains from surface initiators in principle allows much more
      dense polymer surface layers to be created than can be produced by grafting of
      whole (self-excluding) chains. We have utilized aqueous atom transfer radical
      polymerization to graft a series of cleavable hydrophilic poly(N
      isopropylacrylamide) (PNIPAM) homopolymers and block copolymers of substituted
      acrylamides from polystyrene latex to give brushes of controlled MW and surface
      density. Average chain separations much less than their free solution radii of
      gyration have been achieved. Exposure to radiolabeled single proteins or to whole
      plasma and subsequent analysis by SDS-PAGE shows that PNIPAM brushes decrease
      protein adsorption relative to the latex surface or other substituted
      polyacrylamides. The PNIPAM brushes exhibit a second-order phase transition
      around 30 degrees C as reflected by a decrease in the hydrodynamic thickness of
      the brush at higher temperatures. Total plasma protein adsorption is increased at
      40 degrees C compared to 20 degrees C but there is significant differential
      adsorption behavior among the proteins detected by gel-electrophoresis analysis.

PMID- 15503631
TI  - Design and characterisation of new nanoparticulate polymer blends for drug
      delivery.
AB  - The aim of the present work was the design of novel nanoparticle compositions
      based on poly(lactic acid/glycolic acid) (PLGA): poloxamer and PLGA: poloxamine
      blend matrices. For this purpose, we have applied a modified solvent diffusion
      technique that allows the preparation of the nanoparticles without the use of
      high energy sources. Nanoparticles have been prepared with different PLGA:
      poloxamer and PLGA: poloxamine ratios using PEO-derivatives with different
      molecular weights (Mw) and hydrophilia-lipophilia balance (HLB) values. Our
      results show that the physicochemical characteristics of the nanoparticles, such
      as size and zeta potential, are influenced by the type of PEO-derivative
      associated to the PLGA matrix. The 1H-NMR analysis of the different nanoparticle
      compositions showed that the extent of incorporation of the PEO-derivative
      depends strongly on its HLB and also on the nanoparticles preparation conditions.
      The capacity of these nanoparticles as drug delivery devices was evaluated using
      bovine insulin as a model drug. The insulin-encapsulation efficiency was shown to
      be dependent on the composition of the nanoparticles, those containing
      hydrophilic PEO-derivatives being the most effective in entrapping the drug
      molecules. The formation of the blend system displayed positive effects on the
      release characteristics of the nanoparticles. Nanoparticles exhibited a reduced
      initial burst and a nearly linear, constant release rate over a time period of
      two weeks.

PMID- 15503632
TI  - Surface characteristics of block-type copolymer composed of semi-fluorinated and
      phospholipid segments synthesized by living radical polymerization.
AB  - A series of random and block copolymers composed of hydrophilic and hydrophobic
      monomer units have been synthesized by the free and living radical polymerization
      methods, respectively. The hydrophilic monomer unit, 2-methacryloyloxyethyl
      phosphorylcholine (MPC), was selected because the MPC polymers are well-known for
      their excellent bio- and blood compatibilities. The semi-fluorinated monomer,
      2,2,2-trifluoroethyl methacrylate (TFEMA), was used as the hydrophobic monomer
      unit. Several analyses of the copolymer surface showed that the TFEMA unit was
      concentrated at the outermost surface on the random copolymer surface and
      characteristics of MPC unit was dominant on the block copolymer with a low-MPC
      unit composition in the dry state. A reorientation of the MPC unit occurred
      dynamically in the wet state because of the strong hydrophilicity of the MPC
      units. In the case of the block copolymer with a low-MPC-unit composition, the
      surface was covered with the MPC units in the wet state. As a result, the amount
      of the adsorbed bovine plasma fibrinogen and bovine serum gamma-globulin on the
      block copolymer surface was reduced dramatically.

PMID- 15503633
TI  - Tissue responses to thermally-responsive hydrogel nanoparticles.
AB  - Thermally-responsive hydrogel nanoparticles of poly(N-isopropylacrylamide)
      (PNIPAM) and hydroxypropyl cellulose (HPC) have been synthesized. The particle
      size has been correlated to surfactant concentration and polymer concentration
      using dynamic laser light scattering techniques. The tissue compatibility of
      these hydrogel nanoparticles has been evaluated by comparing with poly-L-lactic
      acid and polystyrene nanoparticles using a mouse implantation model. Our results
      suggested that both PNIPAM and HPC nanoparticles triggered lesser inflammatory
      and fibrotic responses among all nanoparticles tested. It is likely that these
      hydrogel nanoparticles may be suitable for tissue augmentation or drug-delivery
      devices.

PMID- 15503634
TI  - Gene delivery: intelligent but just at the beginning.
AB  - Gene therapy is used to treat genetic disorders, which may be achieved both ex
      vivo and in vivo. Gene-delivery systems usually include a carrier system which
      both protects the gene expression plasmid and allows its extracellular and
      intracellular trafficking. Viruses are used in most of the clinical trials today;
      however, they do have important drawbacks. Non-viral vectors based on lipids,
      water-soluble polycations, other non-condensing polymers and nano- or
      microparticles/capsules have been proposed. Cationic polymers, especially
      carrying novel targeting ligands. are receiving increasing attention. Intelligent
      polymers with temperature, pH, and light sensitivities for a controllable and
      effective non-viral transfection have recently been introduced but are just at
      the beginning. Our preliminary studies showed that block copolymers of N
      isopropylacrylamide-acrylic acid with poly(ethylene imine) could be one example
      of these novel non-viral vectors.

PMID- 15503635
TI  - Design of highly specific ligands of fibrin for therapeutic applications.
AB  - The work presented here is aimed at designing high-affinity ligands for the
      fibrin gamma (312-324) epitope. This epitope is specific for fibrin recognition,
      as it is exposed only on the fibrin surface, while in fibrinogen it is buried in
      the protein bulk. This property makes it very useful for therapeutic
      applications. In fact, it may be exploited in driving systems for targeted
      delivery of thrombolytic drugs toward the specific compartment where they are
      needed. It will then allow avoidance of serious unwanted side effects produced by
      a conventional systemic administration. The approach chosen for designing
      putative ligands is based on the known three-dimensional (3D) structure of the
      epitope. A wide virtual library made up of oligo-peptides and analogues designed
      by a combinatorial approach, on the basis of chemical complementarity criteria,
      has been screened by means of a docking/scoring approach (DOCK program). The
      peculiarity of the problem under study required a considerable effort in finding
      a method enabling the experimental validation of the design work results. In fact
      the selected biological target is absolutely new, so that neither a endogenous,
      nor a synthetic high-affinity ligand is known up to now. It does not allow for
      the validation of computational results by means of classical binding tests based
      on the use of known labeled high-affinity ligands. Preliminary binding essayes
      were so carried out by means of the Plasmon Surface Resonance (PSR) technique.
      The experimental results suggested that most of the molecules predicted to be
      good ligands by means of the selected computational tools, could carry the wanted
      affinity toward the selected target.

PMID- 15503636
TI  - Hyaluronic-acid-based semi-interpenetrating materials.
AB  - In order to enhance the mechanical performances of hyaluronic acid (HA) without
      compromising its biological activity, HA has been interpenetrating with a
      fibrillar collagen scaffold. The semi-interpenetrating materials were obtained by
      mixing HA with different molecular weight and a pepsin-solubilized collagen
      (atelocollagen) solution, and then by inducing collagen fibrillogenesis. Results
      indicate that molecular weight of HA significantly influences the mechanical
      properties of the semi-interpenetrating materials and more specifically stronger
      material results from the use of low-molecular-weight (LMW) HA. According to the
      dynamic mechanical data the composite collagen-LMW HA has a higher elastic
      modulus than collagen, whereas the opposite is true for the high-molecular-weight
      (HMW) HA. This result highlights the role of specific interactions that occur
      between collagen and HA during the gel formation in controlling the network
      mechanical stability. LMW HA may, probably, interact more strongly with collagen
      during the fibrillogenesis process than HMW HA due to the higher mobility of the
      chains and the weaker homologous interactions. Moreover, morphological
      observations showed that LMW HA is intimately interdispersed within the collagen
      network and completely coated the fibrils, which act as mechanical support.

PMID- 15503637
TI  - Housing and homelessness. Introduction.

PMID- 15503638
TI  - Housing problems experienced by recipients of child welfare services.
AB  - This study uses data on the experiences of families involved with child welfare
      services to examine the nature of housing problems and needs among these families
      and whether housing status affects case outcomes. First, the article describes
      the housing difficulties faced by two distinct child welfare service populations:
      families receiving voluntary in-home services and families with children in court
      ordered out-of-home care. Second, the study demonstrates the relationship between
      housing problems and the likelihood of family reunification for children in out
      of-home care. The findings have implications for the delivery of child welfare
      services and the provision of housing assistance to low-income families with
      children.

PMID- 15503639
TI  - Child welfare involvement among children in homeless families.
AB  - An analysis of 8251 homeless children in New York City found that 18% of them
      received child welfare services over the five-year period following their first
      shelter admission, and an additional 6% had a history of having received such
      services before their first shelter admission. Recurrent use of public shelters,
      exposure to domestic violence, older age at first episode of homelessness, and
      larger number of children in a household were associated with an increased risk
      of child welfare involvement. The high rate of crossover between homelessness and
      the child welfare system suggests the need for service coordination for children
      in homeless families.

PMID- 15503640
TI  - Housing characteristics and adequacy of the physical care of children: an
      exploratory analysis.
AB  - This study explored the relationship between housing conditions and the adequacy
      of the physical care of children. The sample included 106 caregivers who were
      participating in a neglect prevention demonstration project in a low-income,
      inner-city neighborhood. Children who lived with caregivers who had unsafe
      housing conditions were less likely to receive adequate physical care. Findings
      confirm the importance of addressing concrete housing conditions as part of an
      ecological approach to preventing child neglect.

PMID- 15503641
TI  - Reaching the hard to reach: innovative housing for homeless youth through
      strategic partnerships.
AB  - This article features three housing programs designed to target the needs of
      youth aging out of child welfare. One program combines housing and treatment to
      move substance-dependent youth off the streets; one combines the resources of
      Urban Peak, the only licensed homeless and runaway youth shelter in Colorado,
      with the Denver Department of Human Services to prevent youth in child welfare
      from discharging to the streets; and one addresses the intense mental health
      needs of this population. It costs Colorado 53,655 dollars to place a young
      person in youth corrections for one year and 53,527 dollars for residential
      treatment. It costs Urban Peak 5378 dollars to move a young person off of the
      streets. This article describes how data have driven program development and
      discusses how policy implications and relationships with the public and private
      sector can leverage additional resources.

PMID- 15503642
TI  - Can't do it alone: housing collaborations to improve foster youth outcomes.
AB  - Research documents that youth transitioning out of the foster care system
      experience a variety of negative outcomes, including homelessness. Housing
      collaborations, which aim to comprehensively address resource and service needs
      for transitioning youth, including permanent connections, education, and
      employment, have resulted in innovative programming and forged new relationships
      among child welfare, social service and housing developers, and providers. This
      article describes the partners, models, and resources several collaborations used
      and their progress and outcomes; shares insights gained; and explores productive
      directions for future work.

PMID- 15503643
TI  - Reunifying families, cutting costs: housing-child welfare partnerships for
      permanent supportive housing.
AB  - In the absence of an adequate supply of affordable, quality housing, child
      welfare agencies are placed in the unenviable position of separating families to
      protect children from the debilitating effects of homelessness. This article
      presents recommendations for costeffective housing-child welfare partnerships
      that will shift the burden of providing adequate housing back to housing
      agencies. These partnerships have the potential to move child welfare agencies
      closer to achieving permanence and well-being for all children.

PMID- 15503644
TI  - Housing plus services: supporting vulnerable families in permanent housing.
AB  - The importance of integrating services with housing to help low-income families
      achieve stability is gaining recognition. The variations in types of existing
      housing and service initiatives have produced a complex language with multiple
      meanings and overlapping definitions. The National Low Income Housing Coalition
      proposes the umbrella term housing plus services to refer to these programs.
      Following a review of the literature on the relationship of housing to child well
      being, the article discusses and illustrates the National Low Income Housing
      Coalition's principles for and typology of housing plus services.

PMID- 15503645
TI  - Bridging the gap between preclinical and clinical studies.

PMID- 15503646
TI  - Mechanisms of vascular dysfunctionin insulin resistance.
AB  - Insulin resistance (IR) has profound, negative effects on the function of
      arteries and arterioles throughout the body. In addition to the obvious link
      between IR and the development of type 2 diabetes, IR-associated dysfunction of
      resistance vessels is associated with arterial hypertension and vascular
      occlusive diseases, such as heart attacks and strokes. IR affects arteries and
      arterioles at both the endothelium and smooth muscle levels. For example, IR
      causes reduced responsiveness of vascular smooth muscle to dilator agents;
      predominantly due to impaired potassium channel function. The common, underlying
      mechanism of vascular dysfunction, at both endothelium and smooth muscle levels,
      appears to involve the augmented availability and subsequent actions of reactive
      oxygen species (ROS). However, in some circulations, other factors, such as
      increased production of, and actions by, constrictor agents also appear to
      restrict normal dilator responses. The underlying cause of augmented ROS
      availability is not completely understood, but vascular inflammatory processes
      appear to be involved. Furthermore, application of superoxide dismutase, a
      specific scavenger of superoxide anion, is able to immediately restore normal
      vascular responsiveness in IR arteries. Additional treatments involving
      behavioral and pharmacological approaches, such as dietary adjustments, weight
      loss, exercise and the use of statins or insulin-sensitizing agents also appear
      to offer some benefit against the detrimental effects of IR.

PMID- 15503647
TI  - PPARs as targets for the modulation of cardiovascular risk factors associated
      with the metabolic syndrome.
AB  - Peroxisome proliferator-activated receptor (PPAR) agonists have long been used
      for the treatment of diabetes and hypercholesterolemia--disorders that give
      individuals a high predisposition for cardiovascular disease. Prevention of the
      onset of the latter can begin when a diagnosis of metabolic syndrome, a pathology
      that groups glucose and lipid disturbances, is made. Although the characteristic
      components of metabolic syndrome (ie, high blood pressure, obesity, dyslipidemia,
      insulin resistance and proinflammatory state) are likely to improve through a
      radical change in lifestyle, a therapeutic approach is also advisable, and the
      PPAR agonists are the first in a growing list of drugs that may be effective in
      the prevention of the development of cardiovascular disease.

PMID- 15503648
TI  - Hypolipidemia induced by PPARalpha agonists: HNF-4alpha as an alternative to
      PPARalpha.
AB  - This critical review examines the putative role played by peroxisome proliferator
      activated receptor alpha (PPARalpha) in the hypolipidemic activity induced by
      peroxisome proliferators/PPARalpha agonists. The hypolipidemic effect of
      peroxisome proliferators mediated in rodents by hepatic PPARalpha activation is
      independent of PPARalpha in humans, and is transduced by direct suppression of
      hepatocyte nuclear factor-4alpha by the CoA-thioesters of hypolipidemic
      peroxisome proliferators. A novel target for hypolipidemic drugs in humans and an
      updated risk assessment for human hypolipidemic drugs are implied.

PMID- 15503649
TI  - Vitamin D analogs: novel therapeutic agents for cardiovascular disease?
AB  - Vitamin D3 plays a key role in regulating calcium and mineral homeostasis in
      support of normal development and maintenance of bone. The classic effects of
      vitamin D3 include promoting absorption of dietary calcium in the gut and,
      through its actions as a steroid endocrine hormone, regulating the synthesis and
      secretion of parathyroid hormone. The effects of the vitamin D3 system are
      mediated through the highly regulated generation of the potent, active metabolite
      1,25-dihydroxyvitamin D3 (calcitriol). Vitamin D3 exerts its effects through the
      vitamin D3 receptor (VDR), a ligand-activated nuclear receptor expressed in a
      wide array of tissue and cell types. Studies performed in mice rendered deficient
      for VDR suggest that calcitriol and VDR may inhibit the renin-angiotensin system
      and reduce blood pressure in the long-term. Clinical studies suggest that
      administration of vitamin D3 analogs produces differential benefit with regards
      to mortality in dialysis patients; other studies suggest that vitamin D3 analogs
      may provide cardiovascular benefit in both dialysis and nondialysis patients.
      This paper reviews clinical and preclinical studies, which suggest that vitamin
      D3 analogs may provide therapeutic utility in the treatment of cardiovascular
      disease independent of those mechanisms typically associated with the vitamin D3
      endocrine system.

PMID- 15503650
TI  - Mechanisms regulating cerebral blood flow as therapeutic targets.
AB  - Regulation of cerebral blood flow (CBF) is critical for the maintenance of neural
      function and hence survival of the organism. Since the brain does not store
      glycogen, unlike muscle, a constant supply of glucose and oxygen are needed for
      the minute-by-minute demands of cerebral function. This review focuses on
      important lipid mediators that act as reciprocal regulators of cerebral artery
      diameter and their potential as targets for therapeutic intervention in diseases
      such as ischemia, stroke and subarachnoid hemorrhage. Cytochrome P450 metabolism
      of arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE) or
      epoxyeicosatrienoic acids (EETs) provides a mechanism for the constriction and
      relaxation of cerebral arteries, respectively. Additionally, EETs have mitogenic
      potential and may contribute to angiogenesis in the brain, which has important
      implications during recovery from cerebral injury. Finally, we discuss novel
      inhibitors of 20-HETE formation and actions as well as interventions to enhance
      EET production in cerebrovascular disease.

PMID- 15503651
TI  - Neuropeptide Y: multiple receptors and multiple roles in cardiovascular diseases.
AB  - Neuropeptide Y (NPY), a sympathetic co-transmitter, acts through multiple G
      protein-coupled receptors (Y1 to y6) to elicit its vast range of effects in the
      cardiovascular, immune, and central and peripheral nervous systems. Initially,
      the focus of the function of NPY in the cardiovascular system involved its acute
      actions, such as vasoconstriction via the Y1 receptor. However, recent studies
      have shown that NPY is a potent growth and angiogenic factor, which acts on
      multiple receptor subtypes. To be more specific, NPY-mediated vascular smooth
      muscle cell growth, leading to neointima formation, involves Y1 and Y1 receptors,
      while the angiogenic effects of NPY include Y2 and Y5 receptor activation. The
      presence of dipeptidyl peptidase IV also influences the cardiovascular responses
      of NPY by acting as a converting enzyme, shifting NPY activities away from Y1.
      Thus, agonists and antagonists aimed at the NPY system represent a new avenue for
      drug treatment, which may help alleviate several cardiovascular disorders in
      which vascular remodeling plays a major role, such as atherosclerosis, restenosis
      following balloon angioplasty, hypertension and peripheral vascular disease.

PMID- 15503652
TI  - The serotonin receptor and transporter as potential therapeutic targets for
      pulmonary hypertension.
AB  - Pulmonary hypertension (PHT) results from compromised pulmonary vasoconstriction
      and vascular remodeling. Serotonin (5-hydroxytryptamine/5-HT) is one of the
      important vasomotor agents, and its importance in the pathogenesis of PHT is
      currently being investigated. In most mammalian species, PHT can result from
      numerous serotonergic drugs, demonstrating that various 5-HT receptor subtypes
      and the 5-HT transporter (5-HTT) contribute to PHT. Both are therefore potential
      therapeutic targets for the treatment of the disorder. This review describes
      current awareness of the roles of 5-HT, the 5-HT receptor and the 5-HTT in PHT.

PMID- 15503653
TI  - Gadofosveset (EPIX/Schering).
AB  - EPIX Medical and Schering are developing gadofosveset, an albumin-binding
      gadolinium-based intravascular magnetic resonance imaging contrast agent, for the
      potential imaging of blood vessels and blood flow, particularly in patients with
      peripheral vascular disease (PVD). By February 2004, US approval of the agent was
      anticipated in October 2004, and in June 2004, Schering filed an MAA in the EU
      for PVD.

PMID- 15503654
TI  - Tolvaptan (Otsuka).
AB  - Otsuka is developing tolvaptan (OPC-41061), an orally active non-peptide
      vasopressin V2 antagonist, as a diuretic for the potential treatment of
      congestive heart failure. By November 2003, tolvaptan was undergoing phase III
      clinical trials.

PMID- 15503655
TI  - Ezetimibe + simvastatin (Merck/Schering-Plough).
AB  - Merck/Schering-Plough Pharmaceuticals has developed and launched ezetimibe +
      simvastatin (Vytorin), a fixed combination tablet of Schering-Plough's
      cholesterol absorption inhibitor ezetimebe (Zetia), and Merck's HMG CoA reductase
      inhibitor simvastatin (Zocor), for the treatment of hypercholesterolemia. The
      drug had been launched in Germany and Mexico by April 2004, and, in July 2004,
      was approved in the US, with expected launch late in 2004.

PMID- 15503656
TI  - ETC-588 (Pfizer).
AB  - Pfizer, following its acquisition of Esperion Therapeutics in the first quarter
      of 2004, is developing ETC-588 as a potential acute treatment for ischemia caused
      by atherosclerosis. Enrollment in phase II trials in patients with acute coronary
      syndrome is complete.

PMID- 15503657
TI  - Mechanisms of hormone-mediated carcinogenesis of the ovary.
AB  - Experimental ovarian carcinogenesis has been investigated in inbred and hybrid
      strains of mice and induced by a diversity of mechanisms including X-irradiation,
      oocytotoxic xenobiotic chemicals, ovarian grafting to ectopic or orthotopic
      sites, neonatal thymectomy, mutant genes reducing germ cell populations, and
      aging. Disruptions in the function of graafian follicles by a variety of
      mechanisms results in a spectrum of ovarian proliferative lesions, including
      tumors. The findings in mutant and genetically engineered mice support the
      concept of a secondary (hormonally mediated) mechanism of ovarian tumorigenesis
      in mice associated with sterility. Multiple pathogenic factors that either
      destroy or diminish the numbers of graafian follicles in the ovary result in
      decreased sex hormone secretion, especially estradiol-17beta, leading to a
      compensatory overproduction of pituitary gonadotrophins, particularly LH, which
      places the mouse ovary at an increased risk for developing tumors in chronic
      studies. The intense proliferation of ovarian surface epithelium and stromal
      (interstitial) cells with the development of unique tubular adenomas in response
      to sterility does not appear to have a counterpart in the ovaries of adult human
      females.

PMID- 15503658
TI  - Peroxisome proliferators and receptor-mediated hepatic carcinogenesis.
AB  - The peroxisome proliferators represent an important group of hepatic carcinogens
      in rodents that act via the nuclear receptor PPARalpha. The primary role of
      PPARalpha in mediating this response had led to the further characterization of
      potential events downstream that likely enable the carcinogenic response,
      including increased peroxisomal fatty acid beta oxidation and the modulation of
      hepatocellular replication and death, either generally or in preneoplastic
      lesions. A cooperative role of Kupffer cell activation has been proposed to
      function in the modulation of hepatocellular proliferation in rodent liver by
      peroxisome proliferators, but data that confirm or refute this proposal are
      mixed. Presently there is no evidence that links the Kupffer cell activation by
      peroxisome proliferators directly to the development of liver tumors. There are
      marked species differences in susceptibility to peroxisomal proliferation, and
      active investigation concerning the molecular basis of these differences
      continues.

PMID- 15503659
TI  - Mechanism of benzene-induced hematotoxicity and leukemogenicity: current review
      with implication of microarray analyses.
AB  - Benzene is a potent human leukemogen but the mechanism underlying benzene-induced
      leukemia remains an enigma due to a number of questions regarding the requirement
      of extraordinarily long exposure, a relatively low incidence of leukemia for
      genotoxicity of metabolites and a narrow dose range for leukemogenicity over
      marrow aplasia (overdoses tend to result in marrow aplasia). Moreover, there were
      previous controversies as to whether the cell cycle is upregulated or suppressed
      by the benzene exposure. Subsequently, it was found that the cell cycle is
      suppressed, but how leukemia develops under such suppression of hemopoiesis
      remains to be clarified. These questions were fortunately resolved with much
      effort. Benzene exposure was found to induce the expression of p21, an
      interlocking counterdevice for cell cycle: due to p53 upregulation, thereby
      inducing the immediate suppression of the kinetics of hemopoietic progenitors
      followed by the prominent suppression of hemopoiesis. Intermittent benzene
      exposure (i.e., cessation of exposure during weekends, for example) allowed an
      immediate recovery from marrow suppression after terminating exposure, which
      induced continuous oscillatory changes in marrow hemopoiesis. Benzene-induced
      leukemia was chiefly due to such an oscillatory change in hemopoiesis, which
      epigenetically developed leukemia more than 1 year later. The mechanisms of
      benzene-induced leukemogenicity seem to differ between wild-type mice and mice
      lacking p53. For p53 knockout mice, DNA damage such as weak mutagenicity or
      chromosomal damage was retained, and such damage induced consequent activation of
      proto-oncogenes and related genes, which led cells to undergo further neoplastic
      changes. In contrast, for wild-type mice carrying the p53 gene, a marked
      oscillatory change in the cell cycle of the stem cell compartment seems to be
      important. Compatible and discriminative gene expression profiling between the
      p53 knockout mice and wild-type mice was observed after benzene exposure by
      microarray analyses.

PMID- 15503660
TI  - CDER photosafety guidance for industry.
AB  - In the Federal Register of January 10, 2000 (65 FR 1399), FDA published a draft
      guidance entitled "Photosafety Testing." The notice gave interested persons an
      opportunity to submit comments. As a result of the comments, certain sections of
      the guidance were reworded to improve clarity. A final guidance was published in
      May 2003. The final guidance further emphasizes that a flexible approach can be
      used to address adverse photoeffects and that specific assays are not required.
      Moreover, it encourages the development of methods that can efficiently be used
      to evaluate human safety. The guidance describes a consistent, science-based
      approach for testing of topically and systemically administered drug products.

PMID- 15503661
TI  - Microvesicular steatosis induced by a short chain fatty acid: effects on
      mitochondrial function and correlation with gene expression.
AB  - Hepatotoxicity characterized by microvesicular steatosis (MVS) is characterized
      by an abnormal accumulation of numerous small cytoplasmic lipid droplets in
      hepatocytes. Fulminant or progressive cases of microvesicular steatosis may lead
      to liver failure and death. Experimentally, short-chain carboxylic acids are
      known to induce microvesicular steatosis. The identification of gene changes that
      correlate with MVS concomitant with biochemical and histological indices could
      provide a better understanding of how this toxicity occurs as well as biomarkers
      that could be used to avoid this toxicity in the future. Sprague-Dawley rats were
      dosed days with cyclopropane carboxylic acid (CPCA) a short-chain fatty acid that
      can induce microvesicular steatosis, and with butyrate, a short chain fatty acid
      that served as a negative control. CPCA initiated microvesicular steatosis while
      butyrate did not. In addition, CPCA inhibited beta-oxidation in a concentration
      dependent manner in vitro and caused a reduction in mitochondrial respiration ex
      vivo; no inhibition was evident with butyrate. Microarray results showed that
      gene expression changes with CPCA resulted in regulation of genes involved in
      beta-oxidation, as well as other genes associated with mitochondrial function.
      Overall, these results support altered hepatic mitochondrial function as a
      mechanism of the toxicity induced by a short-chain fatty acid and may provide
      potential biomarkers for this toxicity.

PMID- 15503662
TI  - The toxicology of HMG-CoA reductase inhibitors: prediction of human risk.
AB  - The discovery that 3-hydroxy-3-methyglutaryl coenzyme A reductase was a rate
      determining step in the biosynthesis of cholesterol led to the discovery of
      inhibitors of this enzyme. To support the development of these agents (statins)
      as potential hypocholesterolemic drugs, a variety of preclinical studies were
      conducted in several animal species. Not unexpectedly due to the central role
      played by mevalonic acid and its products including cholesterol in development
      and maintenance of cellular homeostasis, administration of high dosage levels of
      these agents led to the expression of a broad variety of adverse effects in many
      different tissues. Using the tools of toxicologic pathology and classical risk
      assessment, these varied toxicities were evaluated by many groups relative to the
      conditions of use in human therapy and a perspective was developed on potential
      human risk. These approaches of mechanism-based risk assessment predicted that
      most of the adverse effects observed in animals would not be seen under
      conditions of human use and supported the successful introduction of one of the
      most important classes of human medicines.

PMID- 15503663
TI  - Applications of magnetic resonance microscopy.
AB  - Magnetic resonance imaging (MRI) has enjoyed enormous clinical success since the
      first demonstration of the method more than 30 years ago. An increasing number of
      pharmaceutical manufacturers seeking new biomarkers for assessing drug efficacy
      and toxicity are turning to MRI. A specific application of MRI promises to
      revolutionize pathology for the basic scientist in the same way MRI has forever
      altered the standard of care in the clinical domain. More specifically, this
      application is the use of magnetic resonance microscopy (MRM) in conjunction with
      new staining methodologies that now make MRM routinely available to the widest
      range of investigators.

PMID- 15503664
TI  - Digital microscopy imaging and new approaches in toxicologic pathology.
AB  - Digital microscopy, a comprehensive integration of digital imaging and light
      microscopy, can assist the pathologist to observe, acquire, record, share,
      analyze, and manage pathology image data. To lead the activity for establishing
      new generation digital microscopy capacity, novel concepts and strategies of
      digital pathology information flow and digital pathology platform were designed
      to integrate personal digital pathology microscopy workstations and other
      pathology imaging modalities with centralized data storage/management. In
      addition, a strategy for Web-enabled interactive telepathology that would permit
      global capacity was designed. A novel concept of high content pathology was also
      created to develop an automated tissue microscopy imaging and screening approach.
      These new concepts, strategies, and approaches guided the development and
      implementation of a digital pathology platform, a telepathology platform, and
      automated tissue slide imaging capacity. Digital microscopy photography is now
      able to replace photographic film in toxicologic pathology. Digital pathology and
      telepathology platforms can provide a networked environment for multisite, global
      team participation. Our practice also ascertained the central value of digital
      microscopy which can provide innovative quantitative pathology information and
      data mining capability with various imaging biomarkers via advanced digital image
      processing and pathology informatics; these are now the focus of ongoing
      development.

PMID- 15503665
TI  - Toxicogenomic approach to endocrine disrupters: identification of a transcript
      profile characteristic of chemicals with estrogenic activity.
AB  - Public concerns have been raised in recent years over the possible adverse
      effects that may result from exposure to chemicals in the environment that have
      the potential to interfere with the normal function of the endocrine system in
      wildlife and humans ("endocrine disrupters"). Regulations have been established
      that require the testing of pesticides used in food crops and drinking water
      contaminants, for estrogenicity and other hormonal activities. In the United
      States, the U.S. EPA proposed the Endocrine Disrupter Screening Program, which
      consists of a Tier 1 screening battery of tests that is designed to identify
      chemicals capable of interacting with various hormonal systems, and different
      Tier 2 testing assays that are designed to verify and broaden the Tier 1 results.
      We identify 2 main problems with this approach: (1) the fact that the
      developmental stages that are the most susceptible to endocrine disruption are
      not represented in the screening tier, mainly because developmental effects tend
      to be latent, and there is no way to economically screen in developing models;
      and (2) the expense to screen each chemical to be included in this program. Thus,
      the need arises for an accurate, rapid, and cost effective method for assessing
      the potential endocrine activity of multiple chemicals during development. We
      hypothesize that the largely latent developmental effects of some endocrine
      disruptors are preceded by immediate changes in gene expression in the embryo and
      fetus. Therefore, an approach to assess the potential estrogenic (and other
      steroid hormonal) activity of different compounds is to identify those patterns
      of gene expression elicited in a tissue/organ exposed to these particular classes
      of chemicals. In this paper, the potential utility of such an approach for
      screening and better understanding of mechanism of action for specific chemicals
      with endocrine disrupter activities is presented, using as an example chemicals
      with estrogenic activity.

PMID- 15503666
TI  - Chemical-induced nephropathy: a review of the renal tubulointerstitial lesions in
      humans.
AB  - It is almost ironic that one of the major organs that serves to maintain the
      "internal milieux" by secretion of various toxic agents, can itself become
      injured in the process. The pattern of morphologic renal injury is nonspecific
      and can involve any of the components of the kidney, although the injury and
      subsequent morphologic changes are most commonly noted in the tubules and/or
      interstitium. Of course, unless the drug/toxin is commonly or regularly noted to
      be associated with tubular and/or interstitial injury, the association of the
      drug with the renal changes may be missed and the correlation may not necessarily
      identify causation. For example, if a drug is associated with a renal injury in a
      given individual, it may be quite difficult to prove that the drug is the cause
      of the injury. This scenario is somewhat reminiscent of the test question-is it
      "true-true-related," or "true-true-unrelated"? Sometimes it is only by the
      accrual of a great many examples or correlations, and or dissection of the
      pathophysiology, can it be shown that the drug is directly related to the
      observed morphologic (and subsequent clinical) injury. Renal changes induced by
      chemicals can affect the tubules, interstitium or both. This review of chemically
      induced nephropathy in humans considers acute tubular necrosis, interstitial
      nephritis, and tubulointerstitial nephritis or nephropathy. Because the tubules
      and the interstitium are so intimately related, injury to 1 of these 2 components
      may eventually lead to injury of the other, resulting in tubulointerstitial
      disease.

PMID- 15503667
TI  - Thresholds for the effects of 2-acetylaminofluorene in rat liver.
AB  - To explore for practical thresholds for DNA-reactive carcinogens in rat liver
      carcinogenicity, we have conducted a series of exposure-response studies using 2
      well-studied hepatocarcinogens, 2-acetylaminofluorene (AAF) and
      diethylnitrosamine (DEN). Findings with AAF, including as yet unpublished
      experiments, are reviewed here and related to DEN observations. In these studies,
      we have administered exact intragastric doses during an initiation segment (IS)
      of 12-16 weeks followed in some experiments by phenobarbital (PB) as a liver
      tumor promoter for 24 weeks to enhance manifestation of initiation. The
      cumulative doses (CD) of AAF at the end of ISs ranged from 0.094 to 282.2 mg/kg.
      Our findings for AAF in the IS can be summarized as follows: (1) the earliest
      parameter to be affected with administration of low doses was the appearance of
      DNA adducts (around 4 weeks), followed at higher doses by cell proliferation; (2)
      formation of DNA adducts was nonlinear, with a no-observed effect level (NOEL) at
      a CD of 0.094 mg/kg and a plateau at higher doses (94.1 mg/kg); (3) cytotoxicity
      (necrosis) showed a NOEL at a CD of 28.2 mg/kg; (4) compensatory hepatocellular
      proliferation showed a NOEL at a CD of 28.2 mg/kg and was supralinear at a high
      CD (282.2 mg/kg); (5) formation of preneoplastic hepatocellular altered foci
      (HAF) showed a NOEL at a CD of 28.2 mg/kg, and was supralinear at a high CD
      (282.2 mg/kg); (6) a NOEL (CD 28.2 mg/kg) was found for tumor development and the
      exposure-response was supralinear. We interpret these findings to reflect
      practical thresholds for hepatocellular initiating effects of AAF and exaggerated
      responses at high-exposures doses, as also found for DEN. Thus, mechanisms of
      carcinogenesis can differ between low and high doses.

PMID- 15503668
TI  - Phylogeny of the Nymphalidae (Lepidoptera).
AB  - A generic-level phylogeny for the butterfly family Nymphalidae was produced by
      cladistic analysis of 234 characters from all life stages. The 95 species in the
      matrix (selected from the 213 studied) represent all important recognized
      lineages within this family. The analysis showed the taxa grouping into six main
      lineages. The basal branch is the Libytheinae, with the Danainae and Ithomiinae
      on the next branch. The remaining lineages are grouped into two main branches:
      the Heliconiinae-Nymphalinae, primarily flower-visitors (but including the fruit
      attracted Coeini); and the Limenitidinae (sensu strictu), Biblidinae, and the
      satyroid lineage (Apaturinae, Charaxinae, Biinae, Calinaginae, Morphinae,
      Brassolinae, and Satyrinae), primarily fruit-attracted. Data partitions showed
      that the two data sets (immatures and adults) are very different, and a
      partitioned Bremer support analysis showed that the adult characters are the main
      source of conflict in the nodes of the combined analysis tree. This phylogeny
      includes the widest taxon coverage of any morphological study on Nymphalid
      butterflies to date, and supports the monophyly and relationships of most
      presently recognized subgroups, providing strong evidence for the presently
      accepted phylogenetic scheme.

PMID- 15503669
TI  - Testing the phylogenetic position of a parasitic plant (Cuscuta, Convolvulaceae,
      asteridae): Bayesian inference and the parametric bootstrap on data drawn from
      three genomes.
AB  - Previous findings on structural rearrangements in the chloroplast genome of
      Cuscuta (dodder), the only parasitic genus in the morning-glory family,
      Convolvulaceae, were attributed to its parasitic life style, but without proper
      comparison to related nonparasitic members of the family. Before molecular
      evolutionary questions regarding genome evolution can be answered, the
      phylogenetic problems within the family need to be resolved. However, the
      phylogenetic position of parasitic angiosperms and their precise relationship to
      nonparasitic relatives are difficult to infer. Problems are encountered with both
      morphological and molecular evidence. Molecular data have been used in numerous
      studies to elucidate relationships of parasitic taxa, despite accelerated rates
      of sequence evolution. To address the question of the position of the genus
      Cuscuta within Convolvulaceae, we generated a new molecular data set consisting
      of mitochondrial (atpA) and nuclear (RPB2) genes, and analyzed these data
      together with an existing chloroplast data matrix (rbcL, atpB, trnL-F, and psbE
      J), to which an additional chloroplast gene (rpl2) was added. This data set was
      analyzed with an array of phylogenetic methods, including Bayesian analysis,
      maximum likelihood, and maximum parsimony. Further exploration of data was done
      by using methods of phylogeny hypothesis testing. At least two nonparasitic
      lineages are shown to diverge within the Convolvulaceae before Cuscuta. However,
      the exact sister group of Cuscuta could not be ascertained, even though many
      alternatives were rejected with confidence. Caution is therefore warranted when
      interpreting the causes of molecular evolution in Cuscuta. Detailed comparisons
      with nonparasitic Convolvulaceae are necessary before firm conclusions can be
      reached regarding the effects of the parasitic mode of life on patterns of
      molecular evolution in Cuscuta.

PMID- 15503670
TI  - Molecular phylogenetics and evolution of maternal care in Membracine treehoppers.
AB  - The treehopper subfamily Membracinae (Insecta: Hemiptera: Membracidae) comprises
      the majority of genera and species diversity in the New World tropics. These
      treehoppers exhibit a wide range of social behaviors, making them an excellent
      group for studying patterns of social evolution in insects. However, to date the
      tribal and generic relationships have remained unclear. We reconstructed the
      phylogeny of the Membracinae using a combined mitochondrial (COI, COII, tRNA-Leu,
      and 12S) and nuclear (Wg) gene data set. A total of 2608 aligned nucleotide sites
      were obtained for 112 species, representing 25 of 38 currently recognized genera
      and all four tribes. A strict consensus of five equally parsimonious trees
      recovered the subfamily and three of its four tribes. The majority rule consensus
      tree derived from the Bayesian analyses based on the GTR+I+G and mixed-models
      recovered many clades shared with the parsimony trees and is identical to the
      single best tree inferred from maximum likelihood analysis, aside from the
      rearrangement of one node. A comparison of mitochondrial and nuclear genes
      indicated that Wg provided higher consistency index (CI), data decisiveness (DD),
      partitioned Bremer support (PBS) than any of the mitochondrial genes analyzed.
      The combined mitochondrial and nuclear DNA provide strong support for the
      monophyly of the subfamily and three of its four tribes (Aconophorini,
      Hoplophorionini, and Hypsoprorini). Membracini is paraphyletic with respect to
      Hoplophorionini and contains two lineages, the Membracini sensu strictu and the
      newly resurrected tribe Bolbonotini. Our analyses show that there is a strong
      phylogenetic component to the evolution of maternal care. Given the widespread
      occurrence of maternal care within the subfamily, this trait is estimated to have
      < or = 3 origins, two reversals, and one loss. Our results suggest that the
      evolution of maternal care in insects may not be as evolutionarily labile as
      previously thought.

PMID- 15503671
TI  - Biogeography of the Pistia clade (Araceae): based on chloroplast and
      mitochondrial DNA sequences and Bayesian divergence time inference.
AB  - Pistia stratiotes (water lettuce) and Lemna (duckweeds) are the only free
      floating aquatic Araceae. The geographic origin and phylogenetic placement of
      these unrelated aroids present long-standing problems because of their highly
      modified reproductive structures and wide geographical distributions. We sampled
      chloroplast (trnL-trnF and rpl20-rps12 spacers, trnL intron) and mitochondrial
      sequences (nad1 b/c intron) for all genera implicated as close relatives of
      Pistia by morphological, restriction site, and sequencing data, and present a
      hypothesis about its geographic origin based on the consensus of trees obtained
      from the combined data, using Bayesian, maximum likelihood, parsimony, and
      distance analyses. Of the 14 genera closest to Pistia, only Alocasia, Arisaema,
      and Typhonium are species-rich, and the latter two were studied previously,
      facilitating the choice of representatives that span the roots of these genera.
      Results indicate that Pistia and the Seychelles endemic Protarum sechellarum are
      the basalmost branches in a grade comprising the tribes Colocasieae (Ariopsis,
      Steudnera, Remusatia, Alocasia, Colocasia), Arisaemateae (Arisaema, Pinellia),
      and Areae (Arum, Biarum, Dracunculus, Eminium, Helicodiceros, Theriophonum,
      Typhonium). Unexpectedly, all Areae genera are embedded in Typhonium, which
      throws new light on the geographic history of Areae. A Bayesian analysis of
      divergence times that explores the effects of multiple fossil and geological
      calibration points indicates that the Pistia lineage is 90 to 76 million years
      (my) old. The oldest fossils of the Pistia clade, though not Pistia itself, are
      45-my-old leaves from Germany; the closest outgroup, Peltandreae (comprising a
      few species in Florida, the Mediterranean, and Madagascar), is known from 60-my
      old leaves from Europe, Kazakhstan, North Dakota, and Tennessee. Based on the
      geographic ranges of close relatives, Pistia likely originated in the Tethys
      region, with Protarum then surviving on the Seychelles, which became isolated
      from Madagascar and India in the Late Cretaceous (85 my ago). Pistia and Protarum
      provide striking examples of ancient lineages that appear to have survived in
      unique or isolated habitats.

PMID- 15503672
TI  - A molecular supermatrix of the rabbits and hares (Leporidae) allows for the
      identification of five intercontinental exchanges during the Miocene.
AB  - The hares and rabbits belonging to the family Leporidae have a nearly worldwide
      distribution and approximately 72% of the genera have geographically restricted
      distributions. Despite several attempts using morphological, cytogenetic, and
      mitochondrial DNA evidence, a robust phylogeny for the Leporidae remains elusive.
      To provide phylogenetic resolution within this group, a molecular supermatrix was
      constructed for 27 taxa representing all 11 leporid genera. Five nuclear (SPTBN1,
      PRKCI, THY, TG, and MGF) and two mitochondrial (cytochrome b and 12S rRNA) gene
      fragments were analyzed singly and in combination using parsimony, maximum
      likelihood, and Bayesian inference. The analysis of each gene fragment separately
      as well as the combined mtDNA data almost invariably failed to provide strong
      statistical support for intergeneric relationships. In contrast, the combined
      nuclear DNA topology based on 3601 characters greatly increased phylogenetic
      resolution among leporid genera, as was evidenced by the number of topologies in
      the 95% confidence interval and the number of significantly supported nodes. The
      final molecular supermatrix contained 5483 genetic characters and analysis
      thereof consistently recovered the same topology across a range of six
      arbitrarily chosen model specifications. Twelve unique insertion-deletions were
      scored and all could be mapped to the tree to provide additional support without
      introducing any homoplasy. Dispersal-vicariance analyses suggest that the most
      parsimonious solution explaining the current geographic distribution of the group
      involves an Asian or North American origin for the Leporids followed by at least
      nine dispersals and five vicariance events. Of these dispersals, at least three
      intercontinental exchanges occurred between North America and Asia via the Bering
      Strait and an additional three independent dispersals into Africa could be
      identified. A relaxed Bayesian molecular clock applied to the seven loci used in
      this study indicated that most of the intercontinental exchanges occurred between
      14 and 9 million years ago and this period is broadly coincidental with the onset
      of major Antarctic expansions causing land bridges to be exposed.

PMID- 15503673
TI  - Data partitions and complex models in Bayesian analysis: the phylogeny of
      Gymnophthalmid lizards.
AB  - Phylogenetic studies incorporating multiple loci, and multiple genomes, are
      becoming increasingly common. Coincident with this trend in genetic sampling,
      model-based likelihood techniques including Bayesian phylogenetic methods
      continue to gain popularity. Few studies, however, have examined model fit and
      sensitivity to such potentially heterogeneous data partitions within combined
      data analyses using empirical data. Here we investigate the relative model fit
      and sensitivity of Bayesian phylogenetic methods when alternative site-specific
      partitions of among-site rate variation (with and without autocorrelated rates)
      are considered. Our primary goal in choosing a best-fit model was to employ the
      simplest model that was a good fit to the data while optimizing topology and/or
      Bayesian posterior probabilities. Thus, we were not interested in complex models
      that did not practically affect our interpretation of the topology under study.
      We applied these alternative models to a four-gene data set including one protein
      coding nuclear gene (c-mos), one protein-coding mitochondrial gene (ND4), and two
      mitochondrial rRNA genes (12S and 16S) for the diverse yet poorly known lizard
      family Gymnophthalmidae. Our results suggest that the best-fit model partitioned
      among-site rate variation separately among the c-mos, ND4, and 12S + 16S gene
      regions. We found this model yielded identical topologies to those from analyses
      based on the GTR+I+G model, but significantly changed posterior probability
      estimates of clade support. This partitioned model also produced more precise
      (less variable) estimates of posterior probabilities across generations of long
      Bayesian runs, compared to runs employing a GTR+I+G model estimated for the
      combined data. We use this three-way gamma partitioning in Bayesian analyses to
      reconstruct a robust phylogenetic hypothesis for the relationships of genera
      within the lizard family Gymnophthalmidae. We then reevaluate the higher-level
      taxonomic arrangement of the Gymnophthalmidae. Based on our findings, we discuss
      the utility of nontraditional parameters for modeling among-site rate variation
      and the implications and future directions for complex model building and
      testing.

PMID- 15503674
TI  - Cytogenetics and cladistics.
AB  - Chromosomal data have been underutilized in phylogenetic investigations despite
      the obvious potential that cytogenetic studies have to reveal both structural and
      functional homologies among taxa. In large part this is associated with
      difficulties in scoring conventional and molecular cytogenetic information for
      phylogenetic analysis. The manner in which chromosomal data have been used by
      most authors in the past was often conceptionally flawed in terms of the methods
      and principles underpinning modern cladistics. We present herein a review of the
      different methods employed, examine their relative strengths, and then outline a
      simple approach that considers the chromosomal change as the character, and its
      presence or absence the character state. We test this using one simulated and
      several empirical data sets. Features that are unique to cytogenetic
      investigations, including B-chromosomes, heterochromatic additions/deletions, and
      the location and number of nucleolar organizer regions (NORs), as well as the
      weighting of chromosomal characters, are critically discussed with regard to
      their suitability for phylogenetic reconstruction. We conclude that each of these
      classes of data have inherent problems that limit their usefulness in
      phylogenetic analyses and in most of these instances, inclusion should be subject
      to rigorous appraisal that addresses the criterion of unequivocal homology.

PMID- 15503675
TI  - Modeling compositional heterogeneity.
AB  - Compositional heterogeneity among lineages can compromise phylogenetic analyses,
      because models in common use assume compositionally homogeneous data. Models that
      can accommodate compositional heterogeneity with few extra parameters are
      described here, and used in two examples where the true tree is known with
      confidence. It is shown using likelihood ratio tests that adequate modeling of
      compositional heterogeneity can be achieved with few composition parameters, that
      the data may not need to be modelled with separate composition parameters for
      each branch in the tree. Tree searching and placement of composition vectors on
      the tree are done in a Bayesian framework using Markov chain Monte Carlo (MCMC)
      methods. Assessment of fit of the model to the data is made in both maximum
      likelihood (ML) and Bayesian frameworks. In an ML framework, overall model fit is
      assessed using the Goldman-Cox test, and the fit of the composition implied by a
      (possibly heterogeneous) model to the composition of the data is assessed using a
      novel tree-and model-based composition fit test. In a Bayesian framework, overall
      model fit and composition fit are assessed using posterior predictive simulation.
      It is shown that when composition is not accommodated, then the model does not
      fit, and incorrect trees are found; but when composition is accommodated, the
      model then fits, and the known correct phylogenies are obtained.

PMID- 15503676
TI  - Molecular phylogenetic dating of asterid flowering plants shows early Cretaceous
      diversification.
AB  - We present a phylogenetic dating of asterids, based on a 111-taxon tree
      representing all major groups and orders and 83 of the 102 families of asterids,
      with an underlying data set comprising six chloroplast DNA markers totaling 9914
      positions. Phylogenetic dating was done with semiparametric rate smoothing by
      penalized likelihood. Confidence intervals were calculated by bootstrapping. Six
      reference fossils were used for calibration. To explore the effects of various
      sources of error, we repeated the analyses with alternative dating methods
      (nonparametric rate smoothing and the Langley-Fitch clock-based method),
      alternative tree topologies, reduced taxon sampling (22 of the 111 taxa deleted),
      partitioning the data into three genes and three noncoding regions, and
      calibrating with single reference fossils. The analyses with alternative
      topologies, reduced taxon sampling, and coding versus noncoding sequences all
      yielded small or in some cases no deviations. The choice of method influenced the
      age estimates of a few nodes considerably. Calibration with reference fossils is
      a critical issue, and use of single reference fossils yielded different results
      depending on the fossil. The bootstrap confidence intervals were generally small.
      Our results show that asterids and their major subgroups euasterids, campanulids,
      and lamiids diversified during the Early Cretaceous. Cornales, Ericales, and
      Aquifoliales also have crown node ages from the Early Cretaceous. Dipsacales and
      Solanales are from the Mid-Cretaceous, the other orders of core campanulids and
      core lamiids from the Late Cretaceous. The considerable diversity exhibited by
      asterids almost from their first appearance in the fossil record also supports an
      origin and first phase of diversification in the Early Cretaceous.

PMID- 15503677
TI  - Aligned 18S and insect phylogeny.
AB  - The nuclear small subunit rRNA (18S) has played a dominant role in the estimation
      of relationships among insect orders from molecular data. In previous studies,
      18S sequences have been aligned by unadjusted automated approaches (computer
      alignments that are not manually readjusted), most recently with direct
      optimization (simultaneous alignment and tree building using a program called
      "POY"). Parsimony has been the principal optimality criterion. Given the problems
      associated with the alignment of rRNA, and the recent availability of the doublet
      model for the analysis of covarying sites using Bayesian MCMC analysis, a
      different approach is called for in the analysis of these data. In this paper,
      nucleotide sequence data from the 18S small subunit rRNA gene of insects are
      aligned manually with reference to secondary structure, and analyzed under
      Bayesian phylogenetic methods with both GTR+I+G and doublet models in MrBayes. A
      credible phylogeny of Insecta is recovered that is independent of the
      morphological data and (unlike many other analyses of 18S in insects) not
      contradictory to traditional ideas of insect ordinal relationships based on
      morphology. Hexapoda, including Collembola, are monophyletic. Paraneoptera are
      the sister taxon to a monophyletic Holometabola but weakly supported.
      Ephemeroptera are supported as the sister taxon of Neoptera, and this result is
      interpreted with respect to the evolution of direct sperm transfer and the
      evolution of flight. Many other relationships are well-supported but several taxa
      remain problematic, e.g., there is virtually no support for relationships among
      orthopteroid orders. A website is made available that provides aligned 18S data
      in formats that include structural symbols and Nexus formats.

PMID- 15503678
TI  - [What are relative scales and how can they be used in evaluation of Croatian
      science?].
AB  - The most appropriate way of evaluating the quality of scientific research is peer
      review by competent and objective colleagues. An objective review, however, is
      practically impossible within a small scientific community like the Croatian one,
      and the only solution in this case is internationalization of the process. In
      order to upgrade the objectivity of the evaluation, bibliometric/scientiometric
      indicators can be used, provided they are interpreted by experts in the field.
      The author believes that relative scales based on these indicators are of
      particular relevance for such small scientific communities. They enable
      determination of relative positions of a scientist, or a group of scientists,
      within a given scientific discipline, and for a given indicator, both at the
      international and/or national level. Such relative positions can often serve
      better for more objective evaluation than absolute values of the same indicators.
      An example of relative scales and their use is presented.

PMID- 15503679
TI  - [Helicopter transport of patients from Croatian Adriatic Islands and coastal area
      in the period from 1996 to 2002].
AB  - For most of the Croatian Adriatic islands and coastal area, helicopter is the
      fastest, and for some remote areas the only effective way of patient transport.
      In Croatia, most of the aeromedical transports are performed by helicopters of
      95th Air Force Base. During the post-war period, the number of civilian patients
      transported with those helicopters increased from 56 in 1996 to 311 in 2002, this
      trend continuing in 2003. The majority of these transports were performed in the
      third trimester of the year, the largest number of patients were transported from
      the Island of Hvar, and the most common medical indication for aeromedical
      trasport was trauma. The lack of competent medical escort may have unfavourable
      impact on patient health and flight safety. The increasing trend in requesting
      aeromedical transport would obviously justify the foundation of a specialized
      commercial service to provide both safe transport and competent medical escort.

PMID- 15503680
TI  - [Presence of bcl-2 and p53 proteins in patients with non-Hodgkin's lymphoma at
      Zadar General Hospital].
AB  - AIM: The presence of bcl-2 and p53 was retrospectively analyzed in 37 previously
      untreated patients, diagnosed with non-Hodgkin's lymphoma in the period between
      1980 and 1998. PATIENTS AND METHODS: According to all positivity in analyzed
      preparations, all lymphoma were divided into three categories: negative (-) with
      less than 1 per cent of positive tumor cells for the above-mentioned oncogenes;
      moderately positive (+) with 1 to 50 per cent of positive tumor cells, and
      extremely positive (+ +) with over 50 per cent of tumor cells. RESULTS: Twenty
      seven (73%) patients with non-Hodgkin's lymphoma were bcl-2 negative, seven (19%)
      were bcl-2 positive (+), and only one (3%) patient was extremely positive for bcl
      2. Bcl-2 was present in follicular lymphomas regardless of the intensity, whereas
      its presence was not recorded in other subtypes of indolent lymphomas. Bcl-2 was
      moderately positive (+) in six of 11 patients with follicular lymphoma. As for
      aggressive lymphomas, bcl-2 was present in three patients, one (3%) of them
      diagnosed with follicular lymphoma grade III and moderately positive (+) bcl-2.
      The other two patients were diagnosed with diffuse large B-cell lymphoma, with
      moderate (+) and extreme (+ +) bcl-2 positivity recorded in one patient each. P53
      was negative (-) in six (16%), positive (+) in 27 (73%) and extremely positive (+
      +) in four (11%) patients. Positive p53 was found in patients with non-Hodgkin's
      lymphoma regardless of the level of malignancy. CONCLUSION: This study
      demonstrated that the expression of oncogenes could be determined in the archival
      material of lymph node biopsy. The results on oncogene expression were consistent
      with the expected incidence based on other characteristics of the study
      population.

PMID- 15503681
TI  - [Etiology of atypical pneumonias in 2002. Results of the Croatian Institute of
      Public Health].
AB  - AIM: This investigation was performed at Department of Virology, Croatian
      National Institute of Public Health, the same diagnostic laboratory using the
      same serologic method as in earlier studies (in 1982 and 1992) to determine the
      incidence of the most common agents of atypical pneumonia in Croatia between
      January 1 and December 31, 2002. PATIENTS AND METHODS: The study included 630
      patients from nearly all regions of Croatia with a clinical diagnosis of atypical
      pneumonia based on epidemiologic data, clinical symptoms, laboratory findings and
      chest X-rays. Most of them were from Zagreb (n = 370), followed by those from
      Slavonia, Istria, northwest Croatia, and Dalmatia. In all of them paired sera
      were collected at an interval of two weeks or more and tested for complement
      fixing (CF) antibodies against the most common causative agents of the atypical
      pneumonia syndrome using CF test (micromethod). RESULTS: An etiologic diagnosis
      was established in 25% (158/630) patients (81 male and 77 female). Respiratory
      viruses were the most frequently demonstrated pathogens in 2002, accounting for
      72% of cases (adenoviruses 47%, parainfluenza viruses 14%, influenza viruses 9%
      and respiratory syncytial virus (RSV) 2%). These were followed by Chlamydophila
      (C.) psittaci; (19%), Mycoplasma (M.) pneumoniae; (6%) and Coxiella (C.) burnetii
      (3%). There were 3 cases of double infection: a combination of adenovirus and M.
      pneumoniae, of RSV and parainfluenza virus, and of RSV and M. pneumoniae in one
      patient each. Adenoviral, mycoplasmal and psittacosal pneumonia occurred
      throughout the year; influenza and most of RSV pneumonias occurred in winter
      months. Parainfluenza viruses caused pneumonias throughout the year but were more
      common in winter months. CF test does not distinguish type-specific antibodies to
      parainfluenza viruses. In March, a small epidemic of psittacosis (11 patients)
      was registered in the Split area while was responsible for the high incidence of
      psittacosal pneumonia in 2002. While M. pneumoniae-caused pneumonia occurred
      mainly in children and adolescents, viral pneumonias were distributed across all
      age groups. Psittacosal pneumonia occurred in only one child but was more common
      in adolescents and especially adults. Q-fever pneumonia occurred only in adults.

PMID- 15503682
TI  - [Angiotensin converting enzyme and left ventricular hypertrophy in uremic
      patients: correlation and therapeutic options].
AB  - INTRODUCTION: Anemia has been shown to be a key component of renal failure, as
      well as of the occurrence of left ventricular hypertrophy (LVH), with special
      attention paid to the paracrine mechanism of left ventricular remodelling. AIM:
      The aim of the study was to analyze possible association of serum angiotensin
      converting enzyme (ACE) activity and LVH in hemodialysis patients with anemia
      treated with human recombinant erythropoietin (rHuEpo) during six months. METHOD:
      LV geometry was determined by echocardiographic analysis in 20 hemodialysis
      patients before and after erythropoietin treatment. Serum ACE activity was
      measured by spectrophotometric method using hippyril-l-histidyl-l-leucin as a
      substrate. RESULTS: Serum ACE activity increased to 47.3% in hemodialysis
      patients with LVH as compared to patients with normal LV mass. A significant
      positive correlation was found between the level of ACE activity and LV mass
      index (p=0.004). Six-month erythropoietin treatment of anemia led to a
      significant reduction of LV mass index (p<0.008) and serum ACE activity (p=0.003)
      from the initial values. CONCLUSION: The levels of serum ACE activity are
      associated with LV geometry. Our findings suggested the possibility of
      simultaneous and modest modulation of LV mass and serum ACE activity with rHuEpo
      correction of renal anemia.

PMID- 15503683
TI  - [Pathophysiologic basis of the treatment of neurogenic pain].
AB  - According to the International Association for the Study of Pain (IASP)
      neuropathic pain is "pain initiated or caused by a primary lesion or dysfunction
      or transitory perturbation in the peripheral or central nervous system".
      Neuropathic pain is usually classified according to the etiology, location of the
      lesion, and pain characteristics--individual symptoms and signs, but also
      according to the possible mechanisms involved. Identifying the underlying pain
      mechanisms during the diagnosis becomes essential for treatment strategies. The
      clinical picture of neuropathic pain is similar in many cases, and clinical
      features include: ongoing spontaneous or evoked pain in an area with sensory
      loss, positive sensory symptoms such as allodynia and hyperalgesia, wind-up pain
      following repetitive stimulation, referred pain and abnormal sympathetic
      activity. The understanding of the mechanisms underlying neuropathic pain has
      increased over the last decade. The primary pathophysiologic mechanisms that
      produce pain are: nociceptor sensitization, nerve trunk inflammation, sympathetic
      nervous system involvement, ectopic neuronal discharges, pathologic synaptic
      reorganization--neuroplasticity and central sensitization. In most clinical
      features, there is a complex interaction that involves peripheral and central
      nervous system rather than a single mechanism. Because numerous mechanisms are
      implicated, the traditional approach to pain control using single drug therapy
      may not be most effective, and therapeutic combinations are a better choice.
      Neuropathic pain is poorly responsive to conventional analgesics. In spite of a
      variety of drug classes used to treat neuropathic pain including antidepressants,
      anticonvulsants, antiarrhythmics, opioids, local anesthetic blockers, neuropathic
      pain remains difficult to treat. The possibility to select specific drugs and
      treatments for the individual patient lies in elucidating the relationships
      between clinical neuropathic states and underlying pathophysiologic changes.
      Progress in defining the mechanisms involved in neuropathic pain, based on
      further clinical studies and fundamental investigations, will improve therapeutic
      management of neuropathic pain.

PMID- 15503684
TI  - [Hyperphosphatemia and cardiovascular risk in patients on dialysis].
AB  - Cardiovascular diseases are the leading causes of mortality among patients with
      end-stage renal disease (ESRD), with arterial disease and left ventricular
      hypertrophy being the two principal factors of the high mortality rate in this
      population. In addition to traditional risk factors (age, gender, diabetes,
      hypertension, lifestyle, hyperlipidemia, smoking, hyperhomocystinemia),
      inflammation, oxidative stress and disorders of mineral metabolism may contribute
      to cardiovascular risk in patients with uremic syndrome. High serum phosphate may
      influence vascular calcifications directly and indirectly, by worsening secondary
      hyperparathyroidism. Several treatment options are available for the treatment of
      hyperphosphatemia and secondary hyperparathyroidism in patients with ESRD. The
      treatment approach includes a diet low in phosphorus, with less than 1 g/kg/day
      of protein. Vitamin D supplementation is an important part of treatment.
      Phosphate binding agents are in most of the patients necessary in addition to
      diet. Aluminum hydroxide has been widely used for many years. It is very potent,
      but also very toxic, with severe encephalopathy as the most dangerous side
      effect. Calcium salts are less potent, and were considered safe for use in
      patients on dialysis. However, improvement in the understanding of vascular
      calcifications has demonstrated that calcium overload significantly contributes
      to widespread atherosclerosis in patients with ESRD. Sevelamer-hydrochloride is a
      novel non-aluminum, non-calcium containing phosphate binder, which is capable of
      reducing the levels of phosphorus as well as of low-density lipoprotein
      cholesterol, and increasing high-density lipoprotein cholesterol.

PMID- 15503685
TI  - [Development of peritoneal dialysis at Rijeka Clinical Hospital Center].
AB  - The dialysis population is steadily rising as a consequence of the growing
      incidence of terminal renal failure patients and lack of organs for
      transplantation. Peritoneal dialysis (PD) has become an established form of renal
      replacement therapy. The development of new methods, techniques, PD fluids and
      catheters has significantly lowered the incidence of complications and increased
      the use of PD throughout the world. The development of PD at Rijeka University
      Hospital Center, the incidence of PD patients, their underlying renal disease
      leading to terminal renal failure, demographic characteristics of patients,
      complications of treatment, and causes of discontinuation of PD treatment are
      described. At Rijeka University Hospital Center, PD was introduced in 1963 in
      patients with acute renal failure (ARF), and in 1965 in patients with chronic
      renal failure (CRF). Until June 2002, 149 patients were treated, 71 with ARF and
      78 with CRF. Continuous peritoneal dialysis was introduced at our hospital in
      1978. An increasing number of patients on continuous ambulatory peritoneal
      dialysis (CAPD), altogether 35, was noticed in 1999. Automated peritoneal
      dialysis (APD) was introduced in January 2001. Five patients were treated with
      this method until June 2002. The most common underlying renal diseases in
      patients treated from January 1999 until June 2002 were diabetic nephropathy in
      13 (37.1%) and glomerulonephritis in 11 (31.4%) patients, mean age 55.5 years,
      range 31-75 years, both sexes equally present. The leading cause of complications
      were infections and the main cause of death was cardiovascular disease. Five
      (14.3%) patients received kidney transplants which have been functioning well in
      all of them. Because of the high incidence of complications during the seventies,
      intermittent peritoneal dialysis (IPD) was used only occasionally. A significant
      increase in the number of patients on CAPD was observed in 1999. By the end of
      2001 almost ten percent of patients receiving dialytic treatment were on CAPD.
      The most common complications were peritoneal catheter exit site infection and
      peritonitis, which caused referral to HD treatment in four (11.4%) and death in
      two (5.7%) patients with impossible vascular access. The knowledge and
      availability of different renal replacement therapies allow the choice and
      application of the most appropriate treatment option in individual patients with
      terminal renal failure. In comparison to HD, PD improves the quality of patient's
      life and decreases mortality in the first years of treatment. Patients with
      cardiovascular disease and diabetes, whose incidence is steadily rising, have a
      higher incidence of complications on hemodialysis treatment. In these patients PD
      is preferred, especially if used as the first dialytic treatment modality. PD has
      also provided a means of managing patients with no possibility for vascular
      access for HD treatment. Infective and mechanical complications are the main
      obstacles during PD treatment. Adequate facilities, equipment, educated and well
      trained medical personnel and appropriate selection and thorough education of
      patients are necessary for a successful PD program.

PMID- 15503686
TI  - [Role of transthoracic echocardiography in evaluation of cardiac risk in thoracic
      surgery].
AB  - BACKGROUND AND OBJECTIVE: It is not precisely defined which group of non-cardiac
      surgery patients should undergo transthoracic echocardiography in preoperative
      preparation. This study was prospectively performed to find out whether the
      routine use of echocardiography is justified in patients scheduled for lung
      resection, and to assess its role in cardiac risk evaluation. METHODS: Patients
      classified as ASA III who were identified as having minor or intermediate
      predictors of cardiac risk were included in the study. Based on this triage, 130
      patients underwent transthoracic echocardiography. RESULTS: Intermediate index of
      increased perioperative cardiovascular risk was recorded in 36.2% and low index
      in 63.8% of patients. Preoperative anesthesiologic examination revealed some form
      of cardiac arrhythmia in 28.5%, symptoms of coronary disease in 25.4%;
      hypertension in 52.3%, and chronic obstructive pulmonary disease in 16.9% of
      patients. Transthoracic echocardiography showed the ejection fraction of 60% in
      86.9% and of 40%-49% in only one patient. Left ventricular contractility was
      preserved in 96.2% of patients. Diastolic relaxation was weakened in 42.3% of
      patients. Mild mitral insufficiency was found in 29.2%; aortic stenosis in 1.5%,
      mild aortic insufficiency in 2.3%, mild pulmonary hypertension in 70.8%, and
      severe pulmonary hypertension in only 1.5% of patients. Pulmonectomy was
      performed in 26.9%, lobectomy in 62.3% and segmental tumor resection in 10.8% of
      patients. Only 26.2% of patients had peri- and postoperative complications:
      tachyarrhythmia and atrial fibrillation with rapid ventricular answer in 16.2%,
      hypotension 1.5%; hypertension in 2.3% and hypertension and arrhythmia in 1.5% of
      patients. Three (2.3%) patients died. None of our patients had Goldman's score
      higher than 25; according to Detsky index our patients belonged to 0-15 point
      group, class I, with the foreseen risk %. CONCLUSIONS: Transthoracic
      echocardiography is not justified in the routine preoperative preparation of
      thoracosurgical patients classified as ASA III with clinically minor and
      intermediate indexes of increased cardiovascular risk. It should be done in
      selected patients, primarily those that have history data and clinical picture
      consistent with major indices of an increased cardiovascular risk.

PMID- 15503687
TI  - [Congenital diaphragmatic hernia in older children].
AB  - The incidence of congenital diaphragmatic hernia (CDH) is about 4.8/10,000 live
      births. Its typical clinical presentation is respiratory distress occurring
      immediately after birth or in the first few hours or days of a child's life. It
      is characterized by a high mortality rate. Exceptionally, CDH can occur at an
      older age, its symptoms then frequently reflecting gastrointestinal obstruction
      or mild respiratory symptoms. In such cases CDH presents a far more complex
      diagnostic problem. The paper presents the cases of two girls without typical
      symptomatology, aged 5.5 and 10 years, in whom CDH was detected incidentally upon
      thorough physical examination and chest x-rays. Further radiographic evaluation,
      which included barium contrast study and spiral computed tomography, confirmed
      the suspicion of a left-sided posterolateral diaphragmatic hernia with associated
      intestinal malrotation. Surgical intervention conclusively confirmed a
      diaphragmatic defect at the site of Bochdalek's foramen in both cases. The vital
      capacity of the older girl, which was low before the surgery (VC 1.66 L; 69% of
      predicted), was significantly increased a month after the surgical treatment (VC
      2.25 L; 92% of predicted). The generally expressed view that the clinical onset
      of CDH is rare after the neonatal period seems to be erroneous. Some papers
      report on the clinical presentation of CDH after the neonatal period in as many
      as 13%-14% of infants and young children suffering from CDH. Infants and young
      children with a delayed clinical occurrence of CDH can present with respiratory
      or gastrointestinal symptomatology. Children presenting with gastrointestinal
      symptoms have been shown to be significantly older than those presenting with
      respiratory symptoms. In older children and adolescents, the symptoms and signs
      of CDH, which include acute hernial incarceration, nausea, recurrent vomiting,
      diarrhea, obstipation, acute gastric dilatation, subcostal pain, failure to
      thrive and recurrent chest infections, habitually present a significant
      diagnostic problem. Diagnostic errors are mainly due to the fact that the
      possibility of CDH in that age is totally neglected. The most recurrent
      diagnostic misinterpretations in such cases are pneumonia or massive
      pleuropneumonia, empyema, pneumothorax, lung cysts and bullae, and gastric
      volvulus. Thus, whenever a child presents with uncommon respiratory or
      gastrointestinal symptoms and an anomalous chest x-ray, a differential diagnosis
      of CDH should be considered. Otherwise, an accurate diagnosis in both young and
      older children will most probably be only reached at autopsy. In conclusion, the
      presented cases corroborate the finding that CDH in older children may present
      with scarce symptoms, mostly gastrointestinal, or may be altogether asymptomatic
      and unrecognized until as late as adolescence. However, when a diagnosis of CDH
      has been established, albeit asymptomatic, it must be promptly treated surgically
      in order to prevent complications, such as strangulation or bowel perforation,
      and thus avert a potentially fatal outcome. The size itself of the herniac
      foramen is unlikely to be a determining factor at the time of clinical
      presentation of CDH. Surgical occlusion of CDH may in older children result in an
      improved vital capacity, as such cases are rarely associated with major pulmonary
      hypoplasia. Complications resulting from surgical treatment of CDH in older
      children are more likely to occur in the gastrointestinal system, as a
      consequence of the associated bowel malrotation and inadequate bowel fixation.
      Finally, these two cases corroborate the diagnostic value of accurate history
      taking and thorough physical examination.

PMID- 15503688
TI  - [Bilateral ulnar pseudoarthroses in an adult].
AB  - A case is presented of a 30-year-old woman with right ulnar fracture who
      developed pseudoarthrosis after conservative treatment. Healing occurred after
      osteosynthesis. Four years later she sustained fracture of the left forearm.
      Conservative treatment resulted in ulnar pseudoarthrosis, whereas radius healed
      well. The ulna healed after osteosynthesis. Six years later she had refracture of
      the right ulna, distally to the site of fracture and pseudoarthrosis 10 years
      before. Conservative treatment led to pseudoarthrosis of the right ulna again.
      Osteosynthesis produced good result. The case is interesting, because the same
      person suffered ulnar fracture on three occasions (twice on the right and once on
      the left), without intensive trauma, and pseudoarthrosis developed each time
      after conservative treatment, whereby classic osteosynthesis solved the problems.
      There are no similar report in the literature. The question is whether the
      patients had normal bone structure, and whether conservative treatment should be
      done as a standard theapeutic modality in ulnar fractures.

PMID- 15503689
TI  - [Lymphangioleiomyomatosis].
AB  - Lymphangioleiomyomatosis (LAM) is a progressive and usually fatal interstitial
      lung disease characterized by an abnormal smooth-muscle proliferation in the lung
      and axial lymphatics. It affects almost exclusively young women of childbearing
      age. The presenting features most commonly include dyspnea, symptoms of
      pneumothorax and cough. Less commonly patients can present with chest pain,
      pleural or pericardial effusion and lymphedema. Our patient, a 41-year-old woman,
      complained mainly of fatigue that had lasted for 2 months and finally became
      febrile and dispneic, especially when lying down. Pulmonary diagnostic procedures
      revealed several multicystic destruction of lung parenchyma. There was also
      respiratory insufficiency with O2 saturation of 87% and lung diffusion capacity
      reduced to 48%. The retroperitoneum was filled with neoplastic mass as shown on
      an abdominal CT scan. Pathohistologic analysis of retroperitoneal mass together
      with the radiologic finding of the lungs correlated with the diagnosis of LAM.
      The patient was prescribed corticosteroid therapy, which led to rapid clinical
      improvement. After making a definite diagnosis, the patient was recommended
      further treatment with medroxyprogesterone. This case shows that LAM, although
      rare, can present a diagnostic problem to clinicians and should always be
      considered as one of the diagnostic possibilities in young women with nonspecific
      pulmonary symptoms.

PMID- 15503690
TI  - Be not afraid of change: time to eliminate the corporate practice of medicine
      doctrine.

PMID- 15503691
TI  - An uncertain risk and an uncertain future: assessing the legal implications of
      mercury amalgam fillings.

PMID- 15503692
TI  - Cheap smokes: state and federal responses to tobacco tax evasion over the
      internet.

PMID- 15503693
TI  - FDA: protecting and advancing America's health.

PMID- 15503694
TI  - Exclusive agreements between hospitals and anesthesia providers after Jefferson
      Parish: situation inflammatory or merely volatile?

PMID- 15503695
TI  - Using the written description requirement to limit broad patent scope, allow
      competition, and encourage innovation in biotechnology.
AB  - The biotechnology research and development process is extremely expensive and
      companies must attract investors to this high-risk industry to pay for these
      costs. Biotechnology companies rely on their ability to exclude others from
      exploiting the benefits of their research through patent protection to attract
      these investors. Consequently, they seek strong patent protection for their
      inventions by claiming a broad scope of patent protection for their inventions.
      Biotechnology is an industry where the scope of protection should be limited.
      Science-based technologies exploit the perceived technological opportunities from
      recent scientific developments, concentrating the attention of many inventors on
      the same areas. This poses several unique problems. First, only the first of
      several inventors will receive a patent to the invention. Second, due to publicly
      available, basic techniques, the actual contribution made by the inventor may be
      relatively small. Finally, there is a significant risk that permitting an
      overbroad patent scope may permit original patentees to control a variety of
      improvements and a number of applications. Additionally, a broad scope of
      protection for an invention tends to cause underutilization of many potential
      inventions or improvements. By limiting the scope of protection, one allows
      competitors to utilize these potential inventions or improvements and encourages
      the advancement of the technology. Traditionally, courts have used the scope of
      the disclosure to limit a patent with an overly broad scope of protection. The
      Federal Circuit is correctly applying the written description requirement as part
      of the disclosure to limit broad claim scope in biotechnology patents. The
      written description requirement is separate from the enablement requirement and
      applies to all claims. By requiring a written description to allow a PHOSITA to
      determine the structural characteristics of the claimed invention, the Federal
      Circuit is able limit biotechnology patents with overly broad patent scope.
      Recognizing that particular technologies will become more established as
      biotechnology matures giving rise to different issues in setting the appropriate
      level of patent scope, the court allowed the written description requirement to
      mature in tandem with advances in biotechnology to meet these new developments.

PMID- 15503696
TI  - Epidemiology of spinal cord injury in children and adolescents.
AB  - OBJECTIVE: To describe the unique aspects of the epidemiology of pediatric-onset
      spinal cord injury (SCI). METHODS: The characteristics of persons with SCI
      enrolled in either the Shriners Hospitals for Children SCI database or the
      National SCI Statistical Center database from 1973 through 2002 were evaluated
      based on age at time of injury (0-5 years, 6-12 years, 13-15 years, 16-21 years,
      and 22 years and older). RESULTS: Males comprised a consistently decreasing
      proportion of new cases of SCI, ranging from 83% among persons between 16 and 21
      years of age to only 51% among those aged 0 to 5 years. Among children and
      adolescents (under the age of 22), the proportion of SCI due to motor vehicle
      crashes was higher than in adults (22+ years). Sports, violence, and medical or
      surgical complications also accounted for a significantly greater proportion of
      SCI in teenagers (13-21 years) than in adults. Violence has become the leading
      cause of SCI among African American and Hispanic teenage males (13-21 years),
      whereas vehicular crashes are more common among African American and Hispanic men
      of older ages (22 years of age and above). Approximately one third of new cases
      of SCI in the youngest two age groups (0-5 years, 6-12 years) had cervical
      injuries compared with almost one half in the older age groups (age 13 and
      above). SCI was much more likely to be neurologically complete in younger persons
      (69% age 0-5 years vs 51% age > or = 16 years). CONCLUSION: The pediatric-onset
      SCI population is heterogeneous and exhibits distinct epidemiologic
      characteristics both within the different pediatric age groups and with the adult
      onset SCI population.

PMID- 15503697
TI  - Acute evaluation and management of pediatric spinal cord injury.
AB  - BACKGROUND/OBJECTIVE: Of new spinal cord injuries (SCIs) throughout North
      America, up to 14% occur in children younger than 15 years of age. The purpose of
      this paper is to present several aspects unique to the evaluation and treatment
      of a child with SCI. EVALUATION: Vital signs may be absent along with minimal
      blood loss, indicating upper cervical spine injury that is common in children.
      Lap belt injuries are more prevalent in children, especially since 1984, when
      seat belt laws were enacted, and more children began using a lap belt but no
      shoulder harness. Of children with lap belt injuries, 4% to 39% have significant
      neurologic injuries, and 30% to 50% have associated retroperitoneal injuries.
      Radiographic evaluation is more challenging in children because of the presence
      of normal variants such as C2-C3 pseudosubluxation, which occurs in 9% of
      children younger than 7 years. SCI without radiographic abnormality (SCIWORA) is
      common in children under 10 years of age and is associated with more complete
      neurologic injuries than in cases where the injuries can be seen on radiograph.
      MANAGEMENT: For transportation of children and infants younger than 6 years of
      age, the cervical spine needs to be in a neutral position, and spine boards need
      to be modified to allow for the larger head-to-torso ratio that is present in
      children. Cervical traction with Crutchfield tongs in children <12 years of age
      is associated with dural leaks, and therefore, the use of halo traction with
      modified pin placements is recommended. Indications for surgery are generally the
      same as those for adults in regard to decompression and alignment. The length of
      a spinal fusion for stabilization should be minimized in the thoracolumbar spine
      because of the potential for premature arrest of spinal growth. SUMMARY: The
      differences between children and adults with acute SCI are significant enough
      that caregivers cannot evaluate and treat a child with SCI as they would a small
      adult.

PMID- 15503698
TI  - Bladder and bowel management for the child with spinal cord dysfunction.
AB  - Bladder and bowel management can be a challenge to adults and children with
      spinal cord dysfunction. Children are especially challenging due to their
      everchanging growth and developmental considerations. Bladder/bowel incontinence
      can bring about teasing from a child's peers and lead to social isolation. The
      achievement of continence is a major developmental landmark in the formation of
      social autonomy in children. Providing education and implementation of
      bladder/bowel management programs is essential for a child with neurogenic
      bladder/bowel. This article provides a general overview of common bladder and
      bowel management options for children with spinal cord dysfunction. Both
      traditional and innovative management options for the bladder and bowel will be
      described. Age-appropriate expectations and factors to assess child readiness as
      well as patient and family educational strategies to promote independence when
      implementing bladder and bowel programs are described.

PMID- 15503699
TI  - Altered body composition affects resting energy expenditure and interpretation of
      body mass index in children with spinal cord injury.
AB  - BACKGROUND: Individuals with spinal cord injury (SCI) typically undergo changes
      in their body composition (reduction in lean body mass and an increase in fat
      mass) that can lead to secondary complications associated with diminished
      physical activity and obesity. METHODS: This study used dual energy X-ray
      absorptiometry (DXA) to estimate the total lean tissue mass (LTM), total body
      fat, and total bone mineral content (BMC) to assess the relationship between body
      mass index (BMI), body composition, and resting metabolic rate (RMR) in a group
      of children with SCI who were matched with able-bodied controls for age and sex.
      Body composition and RMR were measured in 18 boys and 9 girls (10-21 years of
      age) who had a SCI in the previous 1 to 3 years and in 27 age- and sex-matched
      controls. RESULTS: Children with SCI had significantly lower mean LTM than
      control subjects (37.6 +/- 9.6 kg and 46.7 +/- 9.2 kg, respectively; P < 0.001)
      and higher percent body fat (26.4 +/- 7.9% and 20.2 +/- 8.5%, respectively; P <
      0.02) as measured by DXA, despite their reduced BMI (18.9 +/- 3.8 kg/m2 and 21.2
      +/- 2.9 kg/m2, respectively; P < 0.01). Children with SCI had lower RMR than the
      controls subjects (1213 +/- 334 kJ/d and 1511 +/- 257 kJ/d, respectively), but
      there was no difference in RMR when adjusted for LTM. CONCLUSION: Children with
      SCI have lower RMRs that are associated with their reduced LTM. The reduction in
      LTM and RMR may predispose children with SCI to relative gains in body fat. BMI
      significantly underestimates body fat in children with SCI.

PMID- 15503700
TI  - Utilizing research in wheelchair and seating selection and configuration for
      children with injury/dysfunction of the spinal cord.
AB  - OBJECTIVE: To determine how research regarding wheelchair and seating selection
      and configuration could be applied to the pediatric population with spinal cord
      injury (SCI) and dysfunction. METHODS: Extensive literature reviews were
      completed on (a) powered mobility options and age-appropriateness for training;
      (b) manual wheelchair configuration, pushrim biomechanics, and propulsion
      ergonomics; and (c) cushion selection and use of pressure-mapping devices. The
      findings in the literature review then were compared with clinical observations
      from Shriners Hospitals for Children, Philadelphia's Seating and Wheelchair
      Clinic. RESULTS/DISCUSSION: A significant amount of research is published on
      propulsion ergonomics and pushrim biomechanics in adults with SCI. However, this
      literature review noted that there was limited research available on cushion
      selection and power mobility configuration. Many of the conclusions drawn from
      these publications are applied to pediatric patients and used during the decision
      making process of wheelchair and cushion selection. However, it is critical to
      tailor the assessment to the pediatric population to meet their medical and
      functional needs. CONCLUSION: Although some of the findings can be correlated to
      the pediatric population, there is a lack of research on wheelchair and seating
      selection and configuration as it specifically relates to the young person with
      SCI and dysfunction. Future studies need to be completed.

PMID- 15503701
TI  - Timed motor test for wheelchair users: initial development and application in
      children with spinal cord injury.
AB  - OBJECTIVE: The objective of this study was to describe the development and
      preliminary results of reliability testing of the timed motor test (TMT), a
      performance-based measure of functional status for children with a spinal cord
      injury (SCI) who use a manual wheelchair. This study will also provide pilot data
      using the TMT to examine the impact of thoracolumbosacral orthoses (TLSO) on
      function in children with a SCI. STUDY DESIGN: Cross-sectional observational
      study. METHODS/PARTICIPANTS: This study enrolled 11 subjects with SCI. The TMT
      consisted of donning a shirt, donning pants, even transfers, uneven transfers,
      and propelling a wheelchair 80 feet and up a ramp of 45 feet. Nine subjects
      completed the TMT with and without a TLSO, and 6 subjects (4 of whom also
      completed the TMT with and without a TLSO) completed the reliability testing.
      RESULTS: Except for donning pants, the intertester and intratester reliability of
      the TMT was fair-to-good with intraclass correlation coefficients (ICCs) of 0.60
      or greater. When wearing a TLSO, participants were slower at donning a shirt,
      donning pants, performing even and uneven transfers, and hallway propulsion (P <
      0.05). There was a preference for not wearing a TLSO for dressing and transfer
      skills. CONCLUSION: In general, the TMT for wheelchair users had fair-to-good
      intertester and intratester reliability. Based on these pilot data, there was an
      increase in time to complete several functional tasks because of the use of a
      TLSO as measured by the TMT in children with a SCI.

PMID- 15503702
TI  - Gait analysis in children and adolescents with spinal cord injuries.
AB  - BACKGROUND/OBJECTIVE: Improving ambulation in patients with spinal cord injuries
      (SCIs) is a major challenge for the clinician. Physical examination can be
      supplemented with biomechanic information from the gait laboratory to
      comprehensively evaluate and improve walking. Gait analysis is an effective
      method to evaluate 3-dimensional dynamic joint range of motion (kinematics) and
      forces (kinetics) occurring at the hip, knee, and ankle/foot. Clinical gait
      analysis has proved to be essential for surgical and rehabilitative planning and
      posttreatment assessment in many neuromuscular disorders. Benefits of gait
      analysis also may apply to walking patients with SCIs. The goal of this study was
      to demonstrate the utility of gait analysis in children and adolescents with
      SCIs. METHODS: Motion analysis evaluations and physical examinations were
      performed on 33 children and adolescents with SCIs (16 males, 17 females). Mean
      age at time of gait analysis was 11.7 years, with an age range of 2.5 to 21
      years. RESULTS: Abnormal kinematic patterns, which were repeatable over several
      years, were demonstrated in the patients with SCI. Gait analysis was beneficial
      in making educated treatment decisions about orthotic prescription, surgery,
      postsurgical evaluation, prescription of new therapy, evaluation of spasticity
      medications, and experimental treatments. Another advantage of gait analysis is
      recording and reviewing changes in gait over time. In our study, 22 of the 33
      patients received a 1-year follow-up gait analysis. Patients followed over
      multiyear intervals have demonstrated characteristic changes in mobility
      patterns, resulting in changes in prescription of mobility aids. The benefits of
      gait analysis are demonstrated by case presentation. CONCLUSION: Improved
      ambulation for patients with SCI can be accomplished with physical therapy,
      orthotics, spasticity management, and surgery. These treatments, as well as
      innovative new areas such as functional electrical stimulation and robotic
      assisted therapy, rely on gait analysis to provide a template of normal walking
      patterns and to measure function and document improvements.

PMID- 15503703
TI  - A survey of chronic pain in the pediatric spinal cord injury population.
AB  - BACKGROUND/OBJECTIVE: Although several reports characterize pain associated with
      adult-onset spinal cord injury (SCI), little is known about the incidence and
      etiology of pain associated with pediatric-onset SCI. The purpose of this study
      was to assess the incidence and type of chronic pain in the pediatric SCI
      population and to evaluate the resulting impact on activities of daily living
      (ADLs). METHODS: Patients attending clinic in a pediatric tertiary care facility
      in a major metropolitan area having sustained an SCI during childhood were asked
      to participate. Participants were assessed using the Adolescent Pediatric Pain
      Tool and the Lansky Play Performance Scale, 2 standardized assessments of pain
      and function, respectively. In addition, a questionnaire designed to characterize
      the population and the types of pain reported was administered. RESULTS: Thirty
      one participants were enrolled with an age range at the time of injury from 5
      months to 18 years. Of this population, 65% reported chronic pain. The pain
      reports were classified as either nocioceptive (48%) or neuropathic (19%).
      Interference with ADLs and play was present in only 1 participant. CONCLUSION:
      Based on these pilot data, pain associated with a pediatric-onset SCI is common.
      The incidence of pain in this study approached the reported incidence of chronic
      pain in adult-onset SCI. In the present population, nocioceptive pain was more
      common than was neuropathic pain. These data suggest that although common,
      chronic pain associated with childhood SCI has a significantly smaller impact on
      daily activities than that reported in the literature for adult-onset SCI.

PMID- 15503704
TI  - Prevalence and etiology of autonomic dysreflexia in children with spinal cord
      injuries.
AB  - OBJECTIVE: To delineate the prevalence, etiologies, clinical manifestations,
      complications, and management of autonomic dysreflexia in individuals who
      sustained spinal cord injury (SCI) as children. METHOD: Retrospective chart
      review. PARTICIPANTS: All individuals with > or = T6 SCI who were injured at 13
      years of age or younger and who were cared for at one pediatric SCI program.
      OUTCOME MEASURES: Outcome measures included prevalence, etiologic factors, and
      symptoms of autonomic dysreflexia as documented in both inpatient and outpatient
      records. Blood pressure and heart rate for observed episodes of autonomic
      dysreflexia also were recorded. RESULTS: Of 121 participants who met the study
      criteria, 62 (51%) had experienced autonomic dysreflexia. The most common causes
      of dysreflexia were urologic (75%) and bowel impaction (18%), and the
      distribution of causative factors were similar in the 3 age ranges (0-5 years, 6
      13 years, and 14-21 years). For all age groups, the most common symptoms were
      facial flushing (43%), headaches (24%), sweating (15%), and piloerection (14%).
      However, headaches (5%) and piloerection (0%), were uncommonly seen in children 5
      years of age and younger. For observed episodes of autonomic dysreflexia, the
      majority (93%) demonstrated blood pressure elevations consistent with published
      guidelines, 50% experienced tachycardia, and 12.5% experienced bradycardia.
      Autonomic dysreflexia was significantly more common in individuals with complete
      lesions and in those who were injured between 6 and 13 years old compared with
      those injured at a younger age. Individuals with cervical injuries were not at
      significantly higher risk of dysreflexia than were those with upper thoracic
      level injuries. However, among individuals with complete lesions, autonomic
      dysreflexia was significantly more common in those with tetraplegia. CONCLUSION:
      Autonomic dysreflexia has a similar prevalence in pediatric-onset SCI compared
      with the adult SCI population. Dysreflexia is diagnosed less commonly in infants
      and preschool-aged children, and these 2 populations may present with more subtle
      signs and symptoms.

PMID- 15503705
TI  - Recognition and management of autonomic dysreflexia in pediatric spinal cord
      injury.
AB  - BACKGROUND: Autonomic dysreflexia (AD) is a well-documented complication of
      spinal cord injury (SCI) at or above the T6 level. However, research into AD has
      focused primarily on the adult. Because research that involves children with SCI
      is scarce, current guidelines may not be appropriate for children. Therefore,
      many episodes of AD may be unrecognized or inappropriately treated. To address
      this issue, Shriners Hospitals for Children undertook the development of a
      protocol specific to children and adolescents. METHOD: A task force was developed
      to look at current literature on AD and blood pressure in children. Utilizing
      this literature and consensus among the task force members, the tools necessary
      to treat children with SCI at risk for AD were developed. RESULTS: The task force
      developed several products intended to assist in the recognition and management
      of AD. These include an event flow sheet for recording incidents of AD, a letter
      for the child's school or primary care physician that provides a brief summary of
      AD and the child's baseline blood pressure, and a policy/protocol with 2 age
      specific algorithms to standardize interventions across the 3 Shriners Hospitals
      in the United States with SCI programs (California, Illinois, and Pennsylvania).
      CONCLUSION: The Shriners Hospitals for Children Task Force on Autonomic
      Dysreflexia in Children with Spinal Cord Injury has developed several tools
      specific to children. However, many questions remain to be answered concerning
      blood pressure norms and the clinical presentation of AD in children.

PMID- 15503706
TI  - Recognition and management of respiratory dysfunction in children with
      tetraplegia.
AB  - Children less than 15 years of age comprise approximately 3% to 5% of all new
      spinal injuries each year. Approximately one third of these children sustain
      injuries to the cervical spine. Respiratory complications of spinal cord injuries
      at the level of C5 and above may include diaphragm dysfunction, retained airway
      secretions, recurrent aspiration, nocturnal hypoventilation, and respiratory
      failure. Although most newly injured children with cervical injuries above the
      level of C5 will require mechanical ventilation acutely, many eventually will be
      able to be weaned from technology. Despite their ability to breathe without
      mechanical support, these children often develop ongoing issues associated with
      respiratory compromise, which interfere with daily activities and can negatively
      affect quality of life. Poor endurance, failure to thrive, recurrent pneumonia,
      and sleep-disordered breathing all may be indications of significant respiratory
      dysfunction. This article describes assessment tools and management strategies
      aimed at supporting optimal health and preventing recurrent complications
      associated with unrecognized or untreated respiratory dysfunction.

PMID- 15503707
TI  - Incidence and degree of hip subluxation/dislocation in children with spinal cord
      injury.
AB  - BACKGROUND/OBJECTIVES: The purpose of this study was to verify the incidence and
      degree of hip subluxation/dislocation in children with spinal cord injury (SCI)
      and determine the association between age of injury and hip
      subluxation/dislocation. METHODS: All children from our SCI database with
      complete data through 2001, who had follow-up of > 2 years and were at least 14
      years of age at follow-up, were included in the study. Hip subluxation was
      defined as a migration index (MI) > 20%. The medial joint space (MJS) was
      measured and considered abnormal if > 7 mm. The patients were divided into 2
      groups: those < or = 10 years of age at the time of injury (group 1) and those >
      10 years of age (group 2). There were 62 patients included in the study: 29 in
      group 1 and 33 in group 2. The mean age at the time of injury was 4.6 years for
      group 1 and 14.3 years for group 2. RESULTS AND CONCLUSION: Forty-eight percent
      of patients had at least one hip with subluxation/dislocation: 93% in group 1 and
      9% in group 2. The mean MI (for those that were abnormal) was 44% in group 1 and
      25% in group 2. The MJS was abnormal in 78% of hips in group 1 and 38% in group
      2. Thirteen patients in group 1 and 1 patient in group 2 underwent surgery to
      better contain the hip. Numerous other radiographic hip irregularities were
      identified. This study demonstrates a high rate of hip subluxation/dislocation in
      children with SCI who had onset of injury before 10 years of age.

PMID- 15503708
TI  - Continent urinary diversion: 10-year experience of Shriners Hospitals for
      Children in Chicago.
AB  - PURPOSE: To review long-term functional results, complications, and patient
      satisfaction in patients with a continent catheterizable urinary diversion.
      MATERIALS AND METHODS: A retrospective chart review and telephone satisfaction
      interviews were conducted. Bladder dysfunction was attributed to neurogenic
      bladder (n = 48: 23 spinal cord injury, 18 myelomeningocele, 4 sacral agenesis, 3
      cerebral palsy), bladder exstrophy (n = 2), posterior urethral valves (n = 1),
      and other (n = 3). Patients underwent continent urinary diversion with either the
      Mitrofanoff principle (appendicovesicostomy, n = 47) or a Monti tube
      (ileovesicostomy, n = 8). Outcomes were assessed by chart review. Patient
      satisfaction was assessed by telephone interview and scored from 1 to 10 on a
      Likert-type scale. RESULTS: Between 1992 and 2003, 54 continent urinary
      diversions were performed on 17 boys and 37 girls. Mean age was 15.3 years
      (range, 7-21 years). An umbilical stoma was created in all patients. Seventy
      three percent (40/54) and 47% (26/54) underwent concomitant bladder augmentation
      and urethral sling procedure, respectively. Mean follow-up was 2.5 years (range,
      3 months to 10 years). Ninety-five percent (51/54) of patients were continent,
      and 5% (3/54) were incontinent from the umbilical stoma after one operation. All
      were compliant with intermittent catheterization. Complications included bladder
      calculi (15%; 8/54), stomal stenosis (9%; 5/54), stomal bleeding (5%; 3/54),
      small bowel obstruction (2%; 1/54), and superficial wound dehiscence (2%; 1/54).
      Seventy-three percent (40/54) of patients were available for telephone interview.
      Of these, 90% (36/40) reported satisfaction, and 10% (4/40) reported
      dissatisfaction; 93% (37/40) reported that they would recommend the procedure to
      others, whereas 7% (3/40) would not. CONCLUSION: In our series, continent urinary
      diversion with the Mitrofanoff principle or Monti tube is associated with high
      continence, compliance, and satisfaction rates and a low complication rate. An
      umbilical stoma was achievable in all patients. Our 10-year experience is
      consistent with other reported series and underscores the successful long-term
      outcome and durability of continent urinary diversions.

PMID- 15503709
TI  - Effect of bracing on paralytic scoliosis secondary to spinal cord injury.
AB  - BACKGROUND: The incidence of paralytic scoliosis subsequent to acquired spinal
      cord injury (SCI) has been reported to range from 46% to 97% in patients injured
      before the adolescent growth spurt. OBJECTIVE: The purpose of this report is to
      review early bracing of children with SCI as a means of preventing or delaying
      surgical fusion. METHODS: Patient records from January 1996 to December 2001 from
      the Shriners Hospitals for Children-Philadelphia were retrospectively reviewed;
      123 patients met the inclusion criteria of cervical or thoracic SCI prior to
      skeletal maturity. Patients were divided into 5 groups based on their
      radiographic curve severity at presentation, and then they were subdivided into a
      group that was managed with prophylactic bracing and a group that was not braced.
      End-points included completion of bracing regimen, surgery, or cessation of
      growth. RESULTS: Forty-two patients presented with a curve < 10 degrees, 29 of
      whom were braced, and 13 who were not. Of the braced group, 13 (45%) went on to
      surgery, whereas 10 (77%) of the nonbraced group had surgical correction (P =
      0.03). Of the patients who were initially braced, the average time to surgery was
      8.5 years, whereas that for the nonbraced group was 4.2 years (P = 0.002). A
      similar trend was seen in the patients who presented with an initial curve
      between 11 degrees and 20 degrees (P < 0.001). There was no significant
      difference between time to surgery for the braced and nonbraced patient groups at
      higher (> 20 degrees) initial curve presentations. CONCLUSION: Bracing of
      children with SCI before significant curve formation (< 20 degrees) delays the
      time to surgical correction of the deformity as it progresses. At smaller curves
      (< 10 degrees), bracing may even prevent the need for surgery. As curve size
      increases (> or = 20 degrees), bracing seems to play a limited role, because it
      does not seem to prevent surgery or delay time to surgical correction.

PMID- 15503711
TI  - Overview of adult outcomes in pediatric-onset spinal cord injuries: implications
      for transition to adulthood.
AB  - OBJECTIVE: To provide an overview of the adult outcomes of individuals with
      pediatric-onset spinal cord injuries (SCIs) and the implications of those
      findings for transition to adulthood. METHOD: Structured interview including
      standardized measures. PARTICIPANTS: Individuals who sustained SCI at < or = 18
      years of age and were > or = 24 years of age at interview; matched community
      controls. OUTCOME MEASURES: A structured interview including demographics and
      medical complications. Standardized measures include the Functional Independence
      Measure, Craig Handicap Assessment and Reporting Technique (CHART), Short Form-12
      (SF-12), and Satisfaction with Life Scale (SWLS). RESULTS: Of 265 individuals
      interviewed (mean age at injury, 13.9 years; mean age at follow-up, 27.8 years),
      67% were males, 87% were white, and 59% had tetraplegia. Results showed that 32%
      had a college degree, 57% were employed, 65% were living independently, and 20%
      were married; the median income was 12,000 dollars. Compared with controls,
      subjects were less likely to live independently, be married, have children, or be
      employed. They showed significantly less community participation, significantly
      lower life satisfaction, and significantly lower perceived physical health.
      Multiple regression analyses were conducted for 5 outcomes (independent living,
      employment, income, CHART total, and SWLS), using demographic factors,
      impairment, medical complications, use of street drugs, and functional
      independence as independent variables. Functional independence and education were
      significantly associated with all five outcomes. Illegal drug use was associated
      with independent living, employment, and SWLS. Race was associated with
      employment and CHART. Medical complications were associated with CHART and SWLS.
      Gender was only associated with living independently, and age at injury was only
      associated with SWLS. Level of injury was not associated with any of the
      outcomes. CONCLUSIONS: Adults with pediatric-onset SCI have adult outcomes that
      are below the level of their peers. These results have implications for improving
      the transition to adulthood for future patients with pediatric-onset SCI.

PMID- 15503710
TI  - Long-term outcome of children with high tetraplegia and ventilator dependence.
AB  - BACKGROUND/OBJECTIVES: Since 1978, 350 children with ventilator dependence,
      including 49 with spinal cord injuries (SCIs), have been followed at the
      University of Michigan C.S. Mott Children's Hospital. Some data were kept on
      these children prospectively and included in various studies relating to their
      outcomes and quality of life. This study was designed to determine physical
      outcomes of children with SCI and long-term mechanical ventilation (LTMV) and to
      determine predictors of quality of life for children with SCI and LTMV. METHODS:
      Prospective data collection and retrospective chart reviews were conducted for
      all 49 children with SCI and LTMV followed at the University of Michigan C.S.
      Mott Children's Hospital from 1978 to 2003. RESULTS: Of the 49 children with SCI
      and LTMV, 25 are alive, 16 have died following initial hospital discharge, and 8
      have been lost to follow-up. Age at injury was under 5 years for 15, 5 to 9 years
      for 12, 10 to 14 years for 9, and over 14 years for 13. Forty had high
      tetraplegia, 7 had low tetraplegia, and 2 had paraplegia. Forty-two had ASIA A
      injuries, and 7 had ASIA D. All were discharged to their own homes or foster
      care. CONCLUSION: Our research studies of children with ventilator dependence
      with and without history of SCI have examined daily activities, perceptions of
      their quality of life, and their health and medical complications. This study
      compares individuals 16 years of age and older with matched control groups of
      those with tetraplegic SCI who do not use ventilators and those with other
      diagnoses who use home ventilation. Overall, these children have done remarkably
      well medically and psychologically.

PMID- 15503712
TI  - Leisure characteristics of the pediatric spinal cord injury population.
AB  - OBJECTIVE: Despite the fact that play is the foundation for growth and
      development, little empirical evidence exists about the leisure characteristics
      of the pediatric spinal cord injury (SCI) population. The purpose of this study
      is to establish such a basis through the examination of leisure interests,
      frequency of participation, and satisfaction with activity in children and
      adolescents with SCI. METHODS: A Questionnaire with open- and closed-ended
      questions for 49 recreation activities was administered to a convenience sample
      of children and adolescents with SCI from Shriners Hospitals for Children,
      Chicago. RESULTS: Data from 66 children and adolescents with SCI demonstrated
      that the higher the intensity level of activity, the lower the participation rate
      among all injury levels. Subjects with C7-T6 lesions spent the most time engaged
      in recreational activities and also had the highest number of activities
      participated in per year. However, those with T7-S4 lesions had significantly
      more hours spent in high-intensity activities. CONCLUSION: The goal is for
      rehabilitation professionals to use this information to further develop
      treatments and interventions specific for the pediatric SCI population.

PMID- 15503713
TI  - Spinal cord injury facts and figures at a glance. August 2004.

PMID- 15503714
TI  - Mammography patient surveys.

PMID- 15503715
TI  - Implant mammography.

PMID- 15503716
TI  - Sonographic markers used to detect frequent trisomies.
AB  - Trisomy 13, 18 and 21 are the 3 most prevalent chromosome abnormalities among
      newborns. A second trimester ultrasound is an important noninvasive method that
      can detect the anomalies. Sonographic markers have been correlated to each of the
      3 trisomies. An increased knowledge and understanding of the different markers
      can improve detection of the different trisomies. The earlier the detection, the
      better clinical treatment can be adapted.

PMID- 15503717
TI  - Perceived research needs and barriers among R.T. educators.
AB  - Full-time R.T. educators were surveyed about perceived research needs and
      barriers and to determine whether educational level and type of employer
      influenced these perceptions. R.T. educators reported needs such as training in
      research, access to space, equipment, research funds and personnel to assist in
      research. Additionally, more than half of survey respondents perceived low levels
      of research support within their work environment and a lack of research time. An
      important finding in this study is that the majority of respondents believe that
      research is important to the profession; however, they also believe research
      negatively impacts their teaching and are unlikely to seek a position that
      emphasizes research.

PMID- 15503718
TI  - Legal trends in imaging.
AB  - As long ago as 400 BC, Hippocrates and his followers recognized that someone must
      oversee the practice of medicine and impose effective consequences when practice
      proves substandard. This article focuses primarily upon negligence law, trends
      toward using imaging in criminal cases and the intersection between the law and
      controversial, cutting-edge uses of imaging. The ways in which the law and
      medicine interact as opponents and as partners are described. After completing
      this article, readers will: Describe the prevalent civil damage cases involving
      radiological practices. Know what can be done to help avoid malpractice lawsuits.
      Be able to identify issues with respect to the current insurance crisis.
      Understand the key roles imaging plays in criminal cases. Be aware of legal
      concerns raised by new technologies. This article is a Directed Reading. See the
      quiz following the conclusion.

PMID- 15503719
TI  - Barium swallow.
AB  - After completing this article, the reader should be able to: Describe the
      functional phases and anatomy of swallowing. Detail common underlying causes of
      dysphagia and their radiographic signs and clinical correlates. List the risk
      factors for gastroesophageal reflux disease. Differentiate the procedures and
      goals of barium swallow from those of modified barium swallow. Predict future
      trends in demand for barium contrast imaging exams related to swallowing
      dysfunction.

PMID- 15503720
TI  - Workplace diversity: a generational view.

PMID- 15503721
TI  - Assessing interest for a radiologist assistant program.

PMID- 15503722
TI  - Registry eligible.

PMID- 15503723
TI  - Making the grade.

PMID- 15503724
TI  - Chex-ray.

PMID- 15503725
TI  - PET and MR show promise in diagnosing Alzheimer disease.

PMID- 15503726
TI  - Patient page. Barium swallow examination.

PMID- 15503727
TI  - Community treatment orders: an uncertain step.

PMID- 15503728
TI  - Why are community treatment orders controversial?
AB  - The use of community treatment orders and other forms of mandatory outpatient
      treatment has been controversial. The debate on the appropriateness of compulsory
      treatment in the community addresses a volatile mix of clinical, social policy,
      legal, and philosophical issues. This paper describes the major sources of
      contention, outlines the position of the protagonists, and where possible,
      attempts to answer some of the questions raised and identify common ground.

PMID- 15503730
TI  - The persistence of folly: a critical examination of dissociative identity
      disorder. Part I. The excesses of an improbable concept.
AB  - OBJECTIVE: To examine the concept of dissociative identity disorder (DID).
      METHOD: We reviewed the literature. RESULTS: The literature shows that 1) there
      is no proof for the claim that DID results from childhood trauma; 2) the
      condition cannot be reliably diagnosed; 3) contrary to theory, DID cases in
      children are almost never reported; and 4) consistent evidence of blatant
      iatrogenesis appears in the practices of some of the disorder's proponents.
      CONCLUSIONS: DID is best understood as a culture-bound and often iatrogenic
      condition.

PMID- 15503729
TI  - Involuntary outpatient commitment, community treatment orders, and assisted
      outpatient treatment: what's in the data?
AB  - OBJECTIVE: Involuntary outpatient commitment (OPC), also referred to as community
      treatment orders or assisted outpatient treatment, is a legal intervention
      intended to improve treatment adherence among persons with serious mental
      illness. This paper reviews the empirical literature on the procedure's
      effectiveness. METHODS: We identified and reviewed all English-language studies
      of OPC and related procedures available in Medline and other bibliographic search
      services. RESULTS: Existing naturalistic and quasi-experimental studies, taken as
      a whole, moderately support the view that the procedure is effective, although
      all do have methodological limitations. Two randomized controlled studies of OPC
      have conflicting findings and are reviewed in detail. CONCLUSIONS: On balance,
      empirical studies support the view that OPC is effective under certain
      conditions, although some of the evidence has been contested and the policy
      remains controversial.

PMID- 15503731
TI  - Prevalence and outcomes of pharmaceutical industry-sponsored clinical trials
      involving clozapine, risperidone, or olanzapine.
AB  - OBJECTIVE: The literature continues to highlight the debate on the ethics and
      merits of trials sponsored by the pharmaceutical industry. This study attempts to
      determine the prevalence and outcomes of industry-sponsored trials involving
      clozapine, risperidone, or olanzapine. METHODS: We searched the literature from
      January 1, 1990, to December 31, 2001, to capture all eligible clinical trials
      involving clozapine, risperidone, or olanzapine. The primary outcome measured was
      the clinical outcome of industry-sponsored studies. Secondary outcome measures
      included the following parameters: disclosure of any sponsorship and financial
      support, author(s) employed by the industry, use of comparator drug(s) within the
      trial, sample size, blinding, and use of placebo. RESULTS: The database comprised
      372 articles. Of these trials, 124 (33.3%) were sponsored by the pharmaceutical
      industry. In general, trials sponsored by Eli Lilly or Janssen had better
      research design than trials not funded by the pharmaceutical industry. With
      regard to authorship, more trials funded by Eli Lilly (74.6%) were coauthored by
      an employee of the company, compared with trials funded by either Janssen (23.3%)
      or Novartis/Sandoz (5.6%). Further, more trials sponsored by Eli Lilly reported
      positive outcomes (92.1%), compared with Janssen-sponsored trials (88.4%) and
      Sandoz/Novartis-sponsored trials (72.2%). No negative results were reported in
      any of the industry-funded trials. CONCLUSIONS: One-third of the published
      clinical trials involving clozapine, risperidone, or olanzapine were funded by
      their respective manufacturer. The reported outcomes of the sponsored trials
      highly favour the manufacturer's product.

PMID- 15503732
TI  - Evaluation of a children's temper-taming program.
AB  - OBJECTIVE: To examine the effectiveness of a group cognitive-behavioural therapy
      program in reducing anger and aggressive behaviour in children. METHOD: Study
      participants were 68 children aged 7 to 13 years and their parents. A total of 12
      groups were run at an outpatient children's mental health centre. The children
      were referred to the groups by their clinician for assistance in reducing their
      aggressive behaviour. We obtained quantitative information on the effectiveness
      of the group from the children and their parents, who completed questionnaires
      before the first session and after the last session. The children completed the
      Children's Inventory of Anger (CIA), and the parents completed the Children's
      Hostility Inventory (CHI). We used t tests and analyses of covariance to test for
      posttreatment differences. RESULTS: Results were available for 56 children. At
      posttreatment, children reported that the intensity of their anger had decreased
      (CIA, t41 = 4.39, P < 0.0001), and parents indicated a reduction in the frequency
      of aggression (CHI-Aggression, t44 = 2.82, P < 0.01) and hostility (CHI
      Hostility, t44 = 4.93, P < 0.0001) in their children. CONCLUSIONS: The group
      program appeared to reduce children's anger and aggression. However, the results
      are preliminary, and further controlled evaluation is required.

PMID- 15503733
TI  - Patient opinions on the benefits of treatment programs in residential psychiatric
      care.
AB  - OBJECTIVE: To assess patients' opinions on the perceived benefit of treatment
      delivered during their stay in a residential facility. METHOD: We administered
      the Opinions on Curative Factors Questionnaire (OCFQ), which was developed from
      previous studies and assesses several treatment modalities and therapeutic
      factors, to a sample of 157 severely ill psychiatric patients admitted to a
      residential facility. RESULTS: All therapeutic factors tested by the OCFQ were
      considered helpful or very helpful by most of those sampled. The item with the
      highest score was "talking to doctor," followed by "free pass," "medication,"
      "visitors," "nonhospital setting," "making friends with patients," "structure of
      daily life," "support from team," and "talking to nurses." The least-valued item
      was "group activities." CONCLUSION: Psychiatric patients consider several
      treatment factors to be helpful, especially those based on individual approaches
      or on a less restrictive therapeutic milieu that allows interactions with the
      outside world. These results may be a valuable contribution to improving
      treatment planning in residential facilities.

PMID- 15503734
TI  - Client and community services satisfaction with an assertive community treatment
      subprogram for inner-city clients in Edmonton, Alberta.
AB  - OBJECTIVES: To evaluate client and agency satisfaction with a specific assertive
      community treatment subprogram, known as inner-city support, developed in
      Edmonton to target the inner-city population, and to determine the demographics
      and potential needs of this population. METHOD: Clients were administered
      questionnaires based on the Client Satisfaction Questionnaire and the
      Satisfaction With Life Scale. We also conducted a face-to-face interview. We
      contacted and similarly surveyed 18 community agencies. RESULTS: The program was
      well received, although areas for improvements included dissemination of
      information and hours of operation. Clients also requested more input regarding
      the development of activities. Clients were predominantly male with a diagnosis
      of schizophrenia comorbid with substance abuse and antisocial personality
      disorders, a history of forensic contact, homeless, and dependent on social
      assistance. CONCLUSION: Among the population with serious and persistent mental
      illness, inner-city clients represent a particularly disadvantaged subpopulation
      that may benefit from specialized community programs.

PMID- 15503735
TI  - Stigma impact on Moroccan families of patients with schizophrenia.
AB  - OBJECTIVES: First, to explore whether in Morocco, a non-Western country, family
      members of patients with schizophrenia suffer from stigma and, if they do, which
      areas of their lives are most affected; and second, to explore family members'
      knowledge about the illness and their attitudes toward the patients. METHODS: The
      study was conducted among 100 family members accompanying patients with
      schizophrenia. We used a heteroquestionnaire that inquired about family members'
      and patients' sociodemographic data, family members' knowledge of the patients'
      illness, their attitudes and behaviours toward the patient, and their perception
      of stigma. RESULTS: Family members' mean age was 47.44 years, SD 12.83; 69% were
      women; 38% had no education; and 77% had no professional activity. Most families
      (76%) reported having no knowledge about the illness. However, the illness was
      considered to be incurable (39%), severe (37%), chronic (80%), and handicapping
      (48%) and was believed to be caused by drug use (25%), stressing life events
      (such as conflict or bereavement; 46%), sorcery (25%), organic disturbance (30%),
      or heredity (23%). We found that most of the families suffer from stigma and
      discrimination. A total of 86.7% reported they have hard lives because of the
      illness, and 72% reported psychological suffering caused by sleep and
      relationship disturbances and a poor quality of life. CONCLUSIONS: In this study,
      we found that Moroccan families of patients with schizophrenia suffer from
      stigma. We found the same results in European, In North American, and in some
      Arab and Islam countries. Despite the belief that traditional societies are more
      supportive of the weak and the sick, stigma is a major burden in addition to that
      of the illness.

PMID- 15503736
TI  - Social phobia among university students and its relation to self-esteem and body
      image.
AB  - OBJECTIVE: To demonstrate the prevalence of social phobia and its relation to
      body image and self-esteem. METHOD: Study participants were 1003 students
      recruited from Cumhuriyet University as a randomized sample. Subjects were
      administered the Diagnostic Interview Schedule-III-Revised (DIS-III-R) Social
      Phobia Scale, the Rosenberg Self-Esteem Scale, and the Multidimensional Body-Self
      Relations Questionnaire (MBSRQ). We analyzed the data, using Fisher's exact chi
      square test. RESULTS: Lifetime prevalence of social phobia among university
      students was 9.6% and past-year prevalence was 7.9%. Self-esteem was lower (P <
      0.05) among those with social phobia than among those without social phobia.
      Students with social phobia had lower scores on the MBSRQ than did those without
      social phobia (P < 0.0001). CONCLUSIONS: The results show that persons with
      social phobia have lower self-esteem and more distorted body image than do those
      without social phobia.

PMID- 15503737
TI  - Hospitalization in the first year of treatment for schizophrenia.
AB  - OBJECTIVE: To determine the rates of hospitalization during the first year of
      treatment for schizophrenia, using an epidemiologic sample. METHOD: We examined
      inpatient and outpatient administrative databases in the province of Nova Scotia
      for cases of schizophrenia (ICD-9 code 295 or 298) newly diagnosed during the
      years 1995 to 1998. We noted the diagnosis site (that is, inpatient or
      outpatient) and hospitalizations in the year following diagnosis. We also
      established links to the clinical database maintained by the Nova Scotia Early
      Psychosis Program (NSEPP). RESULTS: Over the 4-year period, we identified 434
      unique cases from an at-risk population of 320,000 (yielding a yearly average age
      specific incidence rate of 3.3/10,000), of whom 119 had received care from the
      NSEPP. Of the cases, 54% were initially diagnosed while they were inpatients. In
      the year following diagnosis, the overall hospitalization rate, excluding initial
      hospitalizations, was 17%. Patients who were initially diagnosed while inpatients
      had a higher rate of hospitalization in the first year of treatment (25% vs 7%),
      compared with those initially diagnosed while outpatients. This relation was also
      present among patients who received care from the NSEPP. CONCLUSIONS: Of newly
      diagnosed patients with schizophrenia, 46% were not hospitalized at the time of
      initial diagnosis. Of all patients, 17% required hospitalization during the first
      year of treatment, excluding an initial hospitalization, if present.
      Hospitalization rates in the first year were higher among patients initially
      hospitalized and among those with a rural residence. Patients requiring
      hospitalization during the first year form an important target group for improved
      interventions.

PMID- 15503738
TI  - Antidepressant-induced sexual dysfunction treated with vardenafil.

PMID- 15503739
TI  - Reconsidering pimozide for new-onset delusions of parasitosis.

PMID- 15503740
TI  - Gabapentin treatment for premature ejaculation.

PMID- 15503741
TI  - Suspected propranolol-induced delirium.

PMID- 15503742
TI  - Recognizing social anxiety disorder.

PMID- 15503743
TI  - A curious case of neuroleptic malignant syndrome.

PMID- 15503744
TI  - Antipsychotic-induced QTc interval prolongation.

PMID- 15503745
TI  - Using depression inventories: not a replacement for clinical judgment.

PMID- 15503746
TI  - Treatment with risperidone and occurrence of blurred vision: a question of higher
      dosage.

PMID- 15503747
TI  - Late onset neutropenia with clozapine.

PMID- 15503748
TI  - A shortage of health information management professionals: how would we know?
AB  - The introduction of computers, the expansion of health insurance coverage through
      employers and government programs, and the increased use of personal health
      information have created a demand for a new breed of qualified medical record and
      health information personnel. The health information management workforce, which
      is entrusted with accurately coding, maintaining, storing, managing, analyzing,
      and disseminating all personal health information created from health care
      encounters, is reportedly in short supply. Given the complexity in defining and
      enumerating the profession, it is challenging to determine if such a shortage
      exists. There is a lack of uniformity across scope of practice, job titles,
      educational paths, and credentials. We report selected findings from a study of
      the health information management profession in North Carolina illustrating the
      methodologic problems encountered when measuring the supply and demand of this
      workforce. A case is made that greater standardization across these multiple
      facets of the profession would be beneficial to the workforce, and we offer
      recommendations on how this could be accomplished.

PMID- 15503749
TI  - Teacher education professionals as partners in health science outreach.
AB  - Medical school and other health science outreach programs to educate and recruit
      precollege students always have relied on successful collaborative efforts.
      Creighton University shares the value, significance, and strategies of involving
      teacher education professionals in several of its current outreach programs,
      including HPPI, Brains Rule! Neuroscience Expositions, and HHMI Build a Human
      Project. The education department partner serves as an essential team member in
      the development, implementation, assessment, and dissemination of these projects
      to promote science and mathematics achievement and interest in medical careers.
      Specific examples and mistakes to avoid are included.

PMID- 15503750
TI  - Determining the efficacy of resiliency training in the work site.
AB  - Resilience and resiliency training, an approach that encompasses the
      complementary and alternative medicine movement, seems to be an important concept
      and philosophy that can be embraced by allied health professionals. The purpose
      of this study was to determine the efficacy of a worksite resiliency training
      program (personal resilience and resilient relationships [PRRR]) by evaluating
      its impact on innate resilience/reintegration, selected resilient qualities (self
      esteem, locus of control, purpose in life, and interpersonal relations), and job
      satisfaction. The experimental group received the PRRR training, and the control
      group did not receive any training. The PRRR training comprised five 8-hour
      training modules. The study was implemented at a large government organization's
      facility in Northern Utah. A total of 232 participants were assigned randomly by
      work unit into the PRRR training group (n = 123) and the control group (n = 109);
      150 participants (73 in the experimental and 77 in the control group) were
      present at all three data collections and were eligible for analysis. Significant
      and positive change occurred in the experimental group, based on combined survey
      data, with regard to five of the six variables, with job satisfaction being the
      only variable not showing positive change in this group. The control group saw no
      positive effects. The results of the study support the efficacy of the PRRR
      training as implemented in the work site.

PMID- 15503751
TI  - Disability studies and health care curriculum: the great divide.
AB  - Models or paradigms of disability are used to guide health care professionals'
      perceptions so that they can serve people with disabilities, enhance their
      futures, and facilitate the resources they need. Health care curricula, which in
      essence train students to make such decisions, are influenced by these models.
      The medical model, which locates disability within the individual, assumes the
      individual with a disability is a victim who must be cured or made more normal.
      The functional-limitation paradigm expands on the medical model, focusing on the
      interaction of physical or mental limitations with social and environmental
      factors. The economic model, based on the concept of employability, emphasizes a
      health-related inability (or limited ability) to work rather than physical
      functioning of the individual. The sociopolitical model views disability as a
      policy and civil rights issue. Health care professionals face a dilemma as the
      disability rights movement demands a shift in social power from the paternalistic
      view of the medical model to the autonomist view of the sociopolitical model. The
      question is asked if curricula are preparing our future health care professionals
      to distinguish how to view each situation and each individual through the lens of
      the appropriate model.

PMID- 15503752
TI  - Allied health professional students' perceived level of comfort in clinical
      situations that have sexual connotations.
AB  - This study examined the anticipated level of comfort of 1,132 higher education
      students enrolled across physical therapy, occupational therapy, medical
      radiation sciences, rehabilitation counseling, leisure and health sciences, and
      behavioral health science professional courses. Participants were asked to
      indicate their anticipated level of comfort for a range of clinical interactions
      that have sexual implications. More than half of the students anticipated that
      they would not feel comfortable in dealing with the issues raised in 9 of the 19
      sexually themed items. Significant gender differences were identified for some of
      these items. These gender differences should be taken into account when
      developing sexuality curricula. Feelings of discomfort when interacting with
      clients could impede appropriate therapeutic interventions. Further research
      investigating the nature and cause of discomfort in clinical settings is
      required. Studies that examine the usefulness of sexuality education programs in
      increasing practitioner comfort also should be carried out.

PMID- 15503753
TI  - Using CD-ROM technology to increase folic acid knowledge among physician
      assistant students.
AB  - The purpose of this study was to examine the effectiveness of incorporating CD
      ROM technology to increase the knowledge of folic acid among physician assistant
      students. Participants included 76 first-year physician assistant students
      enrolled in a Women's Health course. A pretest and posttest was used to evaluate
      the knowledge gain after viewing the CD-ROM over a 2-week period. Of the 76
      students in the course, 73 completed the pretest and the post-test. Posttest
      scores were significantly better than pretest scores (t = -11.83; p < or =
      0.001), with means 68.63% and 46.18%. Knowledge scores increased by 22.45% from
      pre-test to posttest. Student evaluation results suggested that the CD-ROM (1)
      provided folic acid information in a clear and effective manner, (2) adequately
      covered the folic acid information, (3) increased student awareness and knowledge
      about folic acid, and (4) may promote early commitment by students to recommend
      daily folic acid intake to their patients.

PMID- 15503754
TI  - Pre-athletic training students perform better on written tests with teacher
      centered instruction.
AB  - There are many different methods of instruction used in the academic setting.
      Little experimental research exists examining which mode is more effective in
      educating students. The purpose of this study was to compare scores obtained on
      the written and the practical examinations of students on a single topic taught
      through either a teacher-centered format or a student-centered format. A 2 x 2 x
      6 factorial design was used in this study. Independent variables were teaching
      style (teacher-centered instruction and student-centered instruction), order
      (first or second), and learning style (competitive, collaborative, participant,
      avoidant, dependent, and independent). The dependent variables were the scores
      obtained on a written and a practical examination of gait and crutch fitting.
      Forty pre-athletic training students in their first semester of their first year
      (16 males, 24 females) participated in this study. The Grasha-Reichmann Student
      Learning Style Scale was used to determine the learning styles of the subjects.
      The total subject pool was divided randomly into two groups, one taught by
      teacher-centered instruction and the other by student-centered instruction. Both
      groups took the same written and practical examinations, and scores were
      recorded. A 2 x 2 x 6 fixed model multivariate analysis of variance was
      performed. A difference was observed for teaching style (F2,21 = 5.35, p = 0.01),
      on the combination of written and practical exam scores. A difference also was
      observed on the written examination scores with the teacher-centered format
      producing better results (p < 0.05); but teacher-centered format scores did not
      differ from student-centered scores on the practical examination (p > 0.05).
      Teacher-centered instruction improves written test performance compared with
      student-centered instruction. When initially teaching a skill, direct teacher
      involvement may help students learn and perform better.

PMID- 15503755
TI  - An interdisciplinary learning experience through applied clinical practice with
      community volunteers.

PMID- 15503756
TI  - Automating the process of admissions data collection and analysis.

PMID- 15503757
TI  - The state of prevention in allied health education and practice.

PMID- 15503758
TI  - [Utilization of spaceflight technology on medicinal plant study].
AB  - Utilization of spaceflight technology will benefit the modernization of
      Traditional Chinese Medicine study. Many countries, such as USA or Russia, have
      conducted extensive experimental research with plants in the regenerative life
      support system in space stations as well as the research on breeding or
      chromosomal aberration after spaceflight. The space botany is still in its
      preliminary stage in our country. Research has mainly been focused on breeding
      under space-environment. In addition, many experiments have been conducted with
      the spaceflown plants to investigate the growth, development, biochemical and
      physiological changes, as well as the inheritance and variation. Little has been
      done with regard to the facility development to contain the spaceflying seeds and
      no research has been reported on plant growth in spacecrafts. Medicinal plant
      study has certain characteristics and advantages in our country where small
      biological vessels are developed for the spaceflown seeds, which are then
      distinguished to microgravity group and radiation exposed group with analytical
      instrument. However, research has been carried out in medicinal plant breeding or
      inheritance. In future research, more effort should be directed to the study of
      medicinal plants as an important link of a future biological life support system
      as well as to the health care of astronauts by.

PMID- 15503759
TI  - [Ecological research on resources of Chinese herbal medicine].
AB  - OBJECTIVE: To explore the status and development of the ecological research on
      resources of Chinese herbal medicine. METHOD: The ecological domain related to
      the resources of Chinese Herbal Medicine was Analyzed. RESULT: It was found that
      the weakness of the theoretical study and application were the main problems
      constrained the development of ecological research of Chinese Herbal Medicine.
      CONCLUSION: A new subject, ecology of resources of Chinese herbal medicine, will
      come into being with the development of the theoretical and practical study and
      application of new technology and method.

PMID- 15503760
TI  - [Advances in study on bark of Albizzia julibrissin].
AB  - Cortex Albizziae, the stem bark of the leguminous plant Albizzia julibrissin, is
      specified in Chinese pharmacopoeia as a traditional Chinese medicine used to
      relieve melancholia and uneasiness of body and mind, invigorate the circulation
      of blood and subside a swelling. This article reviews the recent advances in
      chemical constituents and pharmacological activities of Cortex Albizziae.

PMID- 15503761
TI  - [Development of effervescent tablet of Chinese traditional medicine and its
      technology study].
AB  - Effervescent tablets which contain an effervescent mixture of a suitable organic
      acid and an alkali metal bicarbonate and/or carbonate can give out carbon dioxide
      when they meet water. The effervescent tablets for oral solution can be dissolved
      in cool water about 17-20 degrees C, therefore it is convenient to carry and use.
      It also has a good taste for patient with deodorizing agent added. The foam
      produced by external effervescent tablets is usually helpful in killing the local
      bacteria. The review displayed the main supplementary material, preparative
      technique and the study development of effervescent tablets of Chinese
      traditional medicine. Effervescent tablets that have been used to clinic were
      enumerated.

PMID- 15503762
TI  - [Application of adsorption resin separation technique in traditional China
      medicine research].
AB  - Adsorption resin separation is one of the new technologies developed after ion
      exchange resin in the 60's of the 20th century. It was early used in the fields
      of the wastewater treatment, pharmaceutical industry, chemical engineering,
      analytical chemistry, clinical detection and treatment. In recent years, the
      technique of adsorption resin separation has been widely used in research on
      active constituent of traditional China medicine. The recent application was
      reviewed in this paper.

PMID- 15503763
TI  - [Effects of scorpion toxins on the cardiovascular system].
AB  - Being a biologic toxin, scorpion toxins have complicate physiologic and
      pharmalogic actions because of its intricate components. This text reviewed the
      effect of scorpion toxins on endothelial cell function, platelet function,
      microcirculation, atherosclerosis, ironic channel, and cardiac function.

PMID- 15503764
TI  - [Pharmacognostic identification of Cryptolepis buchanaii].
AB  - OBJECTIVE: To supply basis for the establishment of quality standard of
      Cryptolepis buchanaii. METHOD: Characters of crude drugs, microscopic
      characteristic as well as UV spectrum of the herb were studied. RESULT:
      Laticifers were found in the cortex and pith of the stem; much papillary non
      glandular hair was found covering the stomata in the sub-cuticle of the leaf.
      CONCLUSION: The results can be employed as the basis for identifying the herb.

PMID- 15503765
TI  - [Studies of soil embryological characteristics of the Salvia miltiorrhiza of
      Zhongjiang].
AB  - OBJECTIVE: To study the characteristics of the SiO2/R2O3 in non-zonal purple soil
      in the light of the difference between the high yield and low yield of Salvia
      miltiorrhiza. METHOD: Both the high yield and low yield drugs developed from the
      same parental material (k1cy) were chosen in the ecology area in Zhongjiang
      county, Sichuan Province. By using the air-dried drugs as sample, quadrat
      sampling method was used to calculat the production. Gravimetric method,
      volumetric method, and colorimetric method and neutralization titration were used
      to measure the content of adhesive particle colloids element in the soil. And T
      test was used for the variable-difference analysis. RESULT: There was a sharp
      contrast between the production of high yield and low yield drugs (P < 0.001).
      The characteristic value of the high yield soil embryology was much higher than
      that of the low yield soil. CONCLUSION: The characteristic value of the purple
      soil embryology is one of the important factors of the soil adaptability of the
      drug and its quality. The weathering degree of the soil is closely related to the
      yield of the drug.

PMID- 15503766
TI  - [Studies on identification of Gryllotalpa by near-infrared diffuse reflectance
      spectrometry].
AB  - OBJECTIVE: To identify and analyse the different species, same species in
      different regions and confusion species. METHOD: Near-infrared diffuse
      reflectance spectrometry was used. RESULT: Clustering analysis showed that
      clustering relations were far among different Gryllotalpa species and close among
      the same species from different regions, and there were close relations among the
      same species from near regions and between Teleogryllus emmus and G. orientalis.
      CONCLUSION: Near-infrared diffuse reflectance spectrometry method can be used in
      classification and identification of Gryllotalpa.

PMID- 15503767
TI  - [The change of activity of protective enzyme around sprout tumble of Pinellia
      ternate under high temperature stress].
AB  - OBJECTIVE: To study the change of the activity of protective enzyme to avoid
      sprout tumble of Pinellia ternata. METHOD: A high temperature stress was given to
      P. ternata. Then the activity of protective enzyme (SOD, POD and CAT) and the
      content of membrane lipid peroxidation (MDA) were detected after different
      treating days. RESULT AND CONCLUSION: By stress time increasing, the content of
      MDA in lamina and petiole increased obviously, but it increased invisibly in
      tuber. After high temperature stress, the activity of both SOD and CAT decreased
      gradually. The activity of POD increased at first but then decreased rapidly.

PMID- 15503768
TI  - [Study on preparation of beta-cyclodextrin inclusion complex of volatile oil in
      xiongdan xiaoyan capsules].
AB  - OBJECTIVE: To study optimum inclusion conditions for volatile oil from three
      medicinal slices in Xiongdan Xiaoyan capsules. METHOD: Saturated water solution
      method (agitation method), ultrasonic method and rubbing method were studied and
      compared. The preparation conditions of ultrasonic method were investigated by
      the orthogonal test. RESULT: The optimum inclusion conditions of ultrasonic
      method were established. CONCLUSION: The ultrasonic method can be used for
      production of inclusion complex in the factory with high inclusion rate and was
      effectiveness.

PMID- 15503769
TI  - [Studies on chemical constituents in rhizome of Matteuccia struthiopteris].
AB  - OBJECTIVE: To study the chemical constituents in rhizome of Matteuccia
      struthiopteris. METHOD: The compounds were isolated by normal phase silica gel
      chromatography. The structures were identified by physical and spectral data.
      RESULT: Six compounds were isolated and identified as woodwardic acid (1), ergost
      6,22-diene-3beta,5alpha,8alpha-triol (2), apigenin (3), riboflavin (4), 4-O-beta
      D-glucopyranosyl-p-coumaric acid (5), 4-O-beta-D-glucopyranosylcaffeic acid (6).
      CONCLUSION: All the compounds were obtained from this plant for the first time.

PMID- 15503770
TI  - [Studies on water-soluble chemical constituents in root of Achyranthes
      bidentata].
AB  - OBJECTIVE: To study the water-soluble chemical constituents in root of
      Achyranthes bidentata. METHOD: The chemical constituents were isolated by silica
      gel column chromatography and the structures were elucidated by the NMR spectra
      and physico-chemical properties. RESULT: Seven compounds were obtained and
      identified as n-butyl-beta-D-fructopyranoside (I), oleanoic acid (II), 3-O-[beta
      D-glucopyranosyl], oleanoic acid 28-O-beta-D-glucopyranoside (III), allantoin
      (IV), 20-hydroxy ecdysone (V), glutamic acid (VI), 3-O-[beta-D-glucopyranosyl],
      oleanoic acid 28-O-beta-D-glucopyranosyl ester (VII). CONCLUSION: Compounds III
      VII were obtained from this plant for the first time.

PMID- 15503772
TI  - [Studies on quality standards of radix Angelicae dahuricae].
AB  - OBJECTIVE: To work out a qualitay standard of Radix Angelicae dahuricae. METHOD:
      TLC and HPLC were adopted. RESULT: Four coumerin compounds were identified by
      TLC, and the contents of two compounds were determined by HPLC. CONCLUSION:
      Imperatorin, isoimperatorin, byakangelicin and oxypeucedaninhydrate can be found
      simultaneously in Radix Angelicae dahuricae. The contents of imperatorin and
      isoimperitorin are not lower than 0.1% and 0.04% respectively.

PMID- 15503771
TI  - [Study on constituents in rhizome of Astilbe chinensis].
AB  - OBJECTIVE: To study the chemical constituents in rhizome of Astilbe chinensis.
      METHOD: The constituents were isolated with column chromatographies and the
      structures were identified by physicochemical properties and spectral analysis
      (UV, IR, MS, 1H-NMR, 13C-NMR and 2D-NMR). RESULT: The structures were identified
      as bergenin (1), 11-O-galloylbergenin (2), 4-O-galloylbergenin (3), catechin (4),
      respectively. CONCLUSION: Compound 3 was isolated from Astilbe for the first
      time.

PMID- 15503773
TI  - [Determination of linderane in root tuber of Lindera aggregata by HPLC].
AB  - OBJECTIVE: To provide scientific basis for quality control of Lindera aggregata.
      METHOD: HPLC analytical method was established using a Lichrospher C18 column and
      acetonitrile-water (56:44) as the mobile phase, detected at 235 nm. RESULT: The
      linear range of linderane is between 0.0642 - 0.5774 microg, the average recovery
      was 98.4%, RSD1.7% (n = 9). CONCLUSION: Contents of linderane in commercially
      available and collected samples were from 0.028% to 0.123% and from 0.056% to
      0.222% respectively.

PMID- 15503774
TI  - [Study on the interactions between four components in Ligusticum chuanxiong
      rhizome and acceptors on cardiac muscle membrane].
AB  - OBJECTIVE: To study the interactions between four components in Ligusticum
      chuanxiong rhizome and heart cell membrane acceptors. METHOD: Through observing
      the retention characteristics of the four components (tetramethylpyrazine,
      vanillic, chrysophol, ferulic acid) on cell membrane stationary phase (CMSP)
      chromatographic column, whether the components combine with cell membrane
      acceptors was studied, and through further comparing the retention
      characteristics with those of known activators or antagonists corresponding to
      cell membrane acceptors, the kind of acceptor with which one component combines
      was studied. RESULT: Tetramethylpyrazine, vanillic and chrysophol had retention
      on CMSP chromatographic column while ferulic acid hadn't. The retention
      characteristics of tetramethylpyrazine were similar to activator and antagonist
      corresponding to a acceptor, vanillic with beta1 acceptor activator. CONCLUSION:
      Tetramethylpyrazine, vanillic and chrysophol can all combine with cardiac muscle
      membrane acceptors, while ferulic acid can not; tetramethylpyrazine probably acts
      on a acceptor and vanillic acts on beta1 acceptor.

PMID- 15503775
TI  - [Experimental study on anti-pyretic effect of gegen qin lian decoction and its
      compounds].
AB  - OBJECTIVE: To investigate composition principles of Gegen Qin Lian decoction
      through anti-pyretic experiment. METHOD: Pharmacological effects of different
      compounds of Gegen Qin Lian decoction according to six hours temperature response
      index (TRI6) and average top temperature response height (deltaT) after the
      decoction was given to feverish animal model by inactived bacteria suspension.
      RESULT: As for reducing six hour temperature response index, Scutellaria
      baicalensis root was the main effective drug. Pueraria lobata root could enforce
      the effect while Coptis chinensis rhizome and Glycyrrhiza uralensis root
      counteracted it. As for reducing average top temperature response height, the
      Effects of four herbal drugs were the same as for TRI6. CONCLUSION: Of the
      compounds of Gegen Qin Lian decoction, as to the pharmcological anti-pyretic
      effects, the best one is the compound of Scutellaria baicalensis and Pueraria
      lobata roots.

PMID- 15503776
TI  - [Mechanism of isinglass in prevention and treatment of chronic atrophic gastritis
      in rats].
AB  - OBJECTIVE: To investigate the mechanism of isinglass in the prevention and
      treatment of chronic atrophic gastritis (CAG) in rats. METHOD: Animal models of
      SD rats with CAG were made in accordance with the previous experience of combined
      administration of 60% ethanol, 20 mmol x L(-1) sodium deoxycholate and 0.1%
      ammonia water. In prevention groups, sucralfate and isinglass were used as
      preventive therapy while CAG rat model was being made. In the reverse groups,
      sucralfate and isinglass were used to treat rats after establishment of CAG rat
      model. Finally all the rats were executed. Then the length of the proliferation
      zone of the gastric mucosa and serum epidermal growth factors (EGF) and growth
      hormones (GH)level were studied. RESULT: In isinglass prevention groups and high
      dose isinglass reverse group, the length of the proliferation zone of the gastric
      mucosa was very close to that in normal control group (P > 0.05), much better
      than model control group (P < 0.01). In low dose isinglass reverse group, it was
      lower than that in normal control group (P < 0.01), but much better than model
      control group (P < 0.01). In both prevention and reverse groups, serum EGF level
      was higher than that in normal (P < 0.01) and model control group (P < 0.05).
      Serum GH level was the same in every group (P > 0.05). CONCLUSION: The mechanism
      of isinglass in the prevention and treatment of CAG rats lies in revitalizing and
      proliferating gastric mucosal cells by stimulating endogenous EGF secretion.

PMID- 15503777
TI  - [Changes of amino acid content in hippocampus of epileptic rats treated with
      volatile oil of Acorus tatarinowii].
AB  - OBJECTIVE: To study the changes of excitatory and inhibitory amino acid content
      in hippocampus of epileptic rats treated with volatile oil of A. tatarinowii, and
      explore the possible antiepiletic mechanism. METHOD: The volatile oil was
      extracted through Supercritical-CO2 Fluid Extraction (SFE-CO2), and epileptic
      models were built up by kainic acid (KA) lateral ventricle injection. The content
      of amino acid in hippocampus of epileptic rats treated with volatile oil was
      calculated. RESULT: The content of GABA increased and Glu decreased prominently
      (P < 0.05) after volatile oil 35 mg x kg(-1) intraperitoneal injection.
      CONCLUSION: The volatile oil of A. tatarinowii can modulate the balance of
      excitatory and inhibitory amino acid in epileptic rats, thereby exerting its
      antiepileptic effect.

PMID- 15503778
TI  - [Effect of Phragmites communis polysaccharide on the aged-model mice].
AB  - OBJECTIVE: To observe the effect of Phragmites communis polysaccharide on aging
      mice induced by injections of D-gulactose. METHOD: Aging mice were used as
      experimental objective. RESULT: Phragmizes communis polysaccharide could
      obviously increase the activity of CAT, SOD, GSH-PX in blood, lower the levels of
      LPO in plasma and the thick liquid made of grinding the tissues of brain and
      liver, and markedly resist the atrophy of the thymus, spleen and brain tissues of
      aging mice. CONCLUSION: Phragmites communis polysaccharide has good anti-aging
      actions.

PMID- 15503779
TI  - [Studies on pharmacodynamic characteristics of aristolochic acid I in rats].
AB  - OBJECTIVE: To study pharmacodynamic characteristics by oral administration
      aristolochic acid I (AA-I) in rats. METHOD: After one-time oral administration of
      Aristolochiae manshuriensis decoction 10 g x kg(-1) and 125I labeled AA-I
      (containing AA-I 37.2 microg x mL(-1)), whole blood concentration of 125I-AA-I
      and the binding rate of serum albumin were detected in 69 normal wistar male
      rats. Metabolic dynamic parameters were calculated by program 3P87 with a two
      compartment model. The distribution ratio and ID% of nine viscera or tissue were
      measured and compared with other until the 40th day. RESULT: After oral
      administration, AA-I was rapidly absorbed into the blood and reached its peak at
      30 minutes and lasted till 90 minutes. AA-I concentration in the blood gradually
      declined afterwards. 24 hours later, only few AA-I could be detected. By the 10th
      day, 68.5% of AA-I presented as the binding type with serum albumin.
      Pharmacodynamic parameters were calculated as follows: Tmax 0.74 h, Cmax 0.92
      microg x mL(-1), t1/2alpha 0.68 h, t1/2beta 20.46 h, V/F 87.39 mL, CL(s) 5.85 mL
      x h(-1) (0.10 mL x min(-1)). On the other hand, after oral administration AA-I
      was rapidly distributed to all the viscera or tissue, whose peak appeared in 5
      minutes and the vallecula was from 24 to 48 hours. The distribution ratio of AA-I
      rose in the kidney after 24 hours, and it showed the highest level in the kidney
      and in the liver by the 4th day compared with other organs or tissue (P < 0.05).
      However, the distribution ratio of AA-I in the kidney became the most dominant
      one after the 30th and the 40th day compared with the others (P < 0.05).
      CONCLUSION: AA-I is rapidly absorbed after oral administration in rats. Its
      distribution has the organ specificity, which is characterized as the possible
      partial metabolism in the liver and the accumulation in the kidney because of
      rather slower elimination. The characteristics may be related to the long term
      nephrotoxicity of AA-I.

PMID- 15503780
TI  - [Investigation on inhibitory and apoptosis-inducing effects of saponins from
      Tribulus terrestris on hepatoma cell line BEL-7402].
AB  - OBJECTIVE: To investigate the inhibitory and apoptosis-inducing effects of
      saponins from Tribulus terrestris (STT) on liver cancer cell line BEL-7402.
      METHOD: MTT, SRB, Wright staining, acridine orange staining, flow cytometry, and
      Immunofluorescence microscopy were used to evaluate the effects of STT on BEL
      7402 cell line. RESULT: SMT had potent inhibitory effect on BEL-7402 cell line in
      a concentration-dependent manner. BEL-7402 cells exibited typical morphological
      alteration of apoptosis when sub-G1 peak could be seen. The expression of Bcl-2
      was decreased in STT treated cells as compared with untreated control cells.
      CONCLUSION: STT exerts its cytotoxic effect on BEL-7402 cells by inducing
      apoptosis.

PMID- 15503781
TI  - [Effect of Tujian decoction on protein kinase C activity in renal cortex in
      diabetic rat].
AB  - OBJECTIVE: To investigate influence of administration of Tujian decoction
      (Chinese herbal medicine) on protein kinase C (PKC) activity, renal function and
      structure in diabetic rat kidney. METHOD: Experimental diabetic nephropathy model
      was induced by nephrectomy combined with streptozotocin (STZ) injection in
      sprague-dawley rat. Tujian decoction (20 g x kg(-1) x d(-1)) and Valsartan (20 mg
      x kg(-1) x d(-1)) were orally administrated respectively for 12 weeks. PKC
      activity was measured by [3H]phorbol 12, 13-dibutyrate ([3H]PDBu) binding assay.
      24 h urine protein excretion (Upro) and renal pathological changes were observed.
      RESULT: In 12th week, diabetic nephrectomized rats developed proteinuria,
      glomerulosclerosis, increased membrane PKC activity (mPKC), decreased cytosol PKC
      (cPKC), and increased ratio of mPKC and cPKC (M/C). Administration of Tujian
      decoction or Valsartan led to a reduction in proteinuria, structural injury, mPKC
      and M/C, and a recovery in cPKC. CONCLUSION: Tujian decoction possesses a
      renoprotective effect on diabetic nephrectomized rat, at least partially via the
      inhibition of PKC activation in renal cortex.

PMID- 15503782
TI  - [Effect of qianlie huichun capsule on microstructure and ultranstructure of
      prostate glandular tissues in rats].
AB  - OBJECTIVE: To investigate the effect of Qianlie Huichun capsule on the
      microstructure and ultranstructure of prostate glandular tissue in the model rat.
      METHOD: Hynertophy of prostate model rat was established by injecting
      testosterone to gelding male rats. After having been fed with Qianlie Huichun
      capsule for 30 days, the rats were killed and prostate tissues were resected for
      pathomorphological studies with microscope and electromicroscope, and the
      diameter of glandular lumer and the height of glandular epithelial cells were
      measured under the microspcope for different groups of rats. RESULT: In the model
      groups, the glandular epithelial cells mutiplycated notably, showing stratified
      and pseudostratified cells that made the glandular lumer cramped. Under the
      electromicroscope, the glandular epithelial cells became high columnor and the
      rough endoreticulum extremely expanded. But in treatment groups, the change of
      the diameter of the glandular lumer and the height of the glandular epithelial
      cells were less remarkable than those in model groups. So the differerence
      between the model group and the treatment groups was remarkable (P < 0.01).
      CONCLUSION: Qianlie Huichun capsule can depress the glandular epithelialceu
      multiplication of prostate gland in model rats.

PMID- 15503783
TI  - The tragedy of Sudan.

PMID- 15503785
TI  - Vanishing Alaska.

PMID- 15503784
TI  - It's not enough to call it genocide.

PMID- 15503786
TI  - Prostate priorities: a new approach to the cancer that 1 in 6 American men will
      eventually get.

PMID- 15503787
TI  - New aspects of premature puberty.

PMID- 15503788
TI  - Contact allergy to Compositae plants in patients with atopic dermatitis.
AB  - To investigate the frequency of Compositae sensitivity is one of the most
      important goals of current dermatology and allergology. We have patch tested 30
      adult patients suffering from "extrinsic" atopic dermatitis with sesquiterpene
      lactone mix and Compositae mix including Compositae mix individual ingredients,
      extracts of arnica (Arnica montana), chamomile (Chamomilla recutita), tansy
      (Tanacetum vulgare), fever few (Tanacetum parthenium) and yarrow (Achillea
      millefolium) as well as with specific series for patients with atopic dermatitis.
      All allergens were purchased from Hermal-Trolab (Reinbek, Germany). There were 6
      (20%) patients positive to Compositae mix only, and 3 (10%) patients positive to
      both Compositae mix and sesquiterpene lactone mix. Among 9 Compositae mix
      sensitive patients 8 (88.8%) were positive to at least 1 of its individual
      ingredients: 5 (55.5%) to chamomile, 4 (44.4%) to arnica, 2 (22.2%) to tansy, and
      2 (22.2%) to fever few. Among Compositae-sensitive patients 78.8% had other
      contact allergies, most often to nickel (33.3%). Since our study represents the
      first report on contact allergy to Compositae among patients with "extrinsic"
      type of atopic dermatitis, it substantiates the statement that atopy represents a
      risk factor for Compositae allergy. In conclusion, the overall prevalence of 30%
      Compositae-sensitive among patients with "extrinsic" atopic dermatitis detected
      in our study represents a basal sesquiterpene lactone mix detection rate of 10%,
      reinforced and safely supplemented by 20% by testing with the Compositae mix.

PMID- 15503789
TI  - [Psychiatric adverse effects induced by recombinant interferon alfa in patients
      with chronic hepatitis C].
AB  - INTRODUCTION: Hepatitis C virus infection is a slowly progressive chronic disease
      and the most common cause of chronic liver disease. Presently, interferon alfa
      based therapies, with or without ribavirin, are standard treatment for chronic
      hepatitis C virus infection. The most troublesome psychiatric side effects of
      interferon therapy in our patients are: insomnia, irritability, anxiety, mood
      changes, short temper, emotional and affective lability, impaired cognitive
      function, apathy, loss of motivation and the most serious depression with or
      without suicidal ideas. MATERIAL AND METHODS: In our study we treated 82 patients
      chronically infected with HCV divided into 3 groups: the first group of 31
      patients (20 male and 11 female) received IFN-alfa in standard doses of 3 MU
      three times a week (t.i.w) during 24 weeks; the second group of 36 patients (25
      male and 11 female) received IFN-alfa, 3 MU t.i.w plus ribavirin 1000-1200 mg per
      day during 24 weeks; the third group of 15 patients (11 male and 4 female)
      received IFN-alfa, 3 MU t.i.w plus ribavirin 1000-1200 mg per day during 48
      weeks. The follow-up period after therapy in all groups lasted 24 weeks. RESULTS:
      During treatment, we observed at least one psychiatric side effect in 21 (26%)
      patients: insomnia in 11 (13%), emotional and affective lability in 9 (11%),
      anxiety, irritability and short temper in 8 (10%), impaired cognitive function in
      7 (8%) apathia and loss of motivation in 6 (7%) treated patients. Depression, the
      most serious side effect, was established in 8 (10%) patients. All of these side
      effects were observed during later stages of treatment (between 5th and 22nd
      weeks of treatment). The incidence of all psychiatric side effects was
      significantly higher in women than in men (p < 0.01). We observed higher
      prevalence of depression among patients with history of alcohol and drug abuse.
      Treatment was temporarily discontinued (from 2 to 4 weeks) in all patients with
      depression, but it was not permanently discontinuated in any patient due to
      psychiatric side effects. CONCLUSION: Interferon causes psychiatric disorders
      that are usually mild and reversible. They disappear either spontaneously, while
      patients are still receiving therapy or after temporary cessation of interferon
      alfa therapy.

PMID- 15503790
TI  - Biological motivations in the neurodynamic structure of psychopathological states
      (experimental approach).
AB  - Some trigger mechanisms of pathological and biological motivations were
      investigated in experimental models of animal behavior (feeding, drinking,
      stereotypic acts, experimental alcoholism, and so on), as well as high level of
      brain-specific molecular synthesis responsible for development of pathological
      motivations. Neurophysiological processes transforming some biological drives to
      pathological motivations are described and discussed.

PMID- 15503791
TI  - [Parent-child parallel nutritional status assessment using silhouette rating
      scales].
AB  - INTRODUCTION: The aim of this study was to determine the validity of silhouettes
      in assessing genetic factors of obesity in school children aged 12-14. MATERIAL
      AND METHODS: 290 primary school students aged 12-14 from Belgrade had undergone
      body height and weight measurements as well as answering questionnaires.
      Silhouette rating scales were used to assess the nutritional status of students
      (6-silhouette scale) and their parents (9-silhouette scale). RESULTS: Significant
      differences in body mass index (BMI) were found among children whose parents had
      been rated "normal" and those rated "problematic". BMI status and gender
      significantly affected assessment of the nutritional status. An interaction
      between factors was found (F (1.230) = 7.017, p < 0.01). The majority of children
      from the normal BMI category (64.5%) selected silhouettes 3 and 4 to describe
      their current appearance. On the other hand, 70% of children with problematic BMI
      selected silhouettes 5 and 6. Girls generally selected significantly smaller
      silhouettes than boys. Girls within the problematic BMI category selected
      significantly bigger silhouettes for their mother's than the other children. Boys
      within the normal BMI category, selected significantly bigger silhouettes
      representing their father's body size. DISCUSSION: According to the results,
      silhouette rating scales appear to be reliable in parallel assessment of the
      nutritional status of children and their parents. This subject can be further
      developed by acquiring data on parents' height and body mass.

PMID- 15503792
TI  - [Collaboration in the field of public health in South Eastern Europe].
AB  - INTRODUCTION: Southeastern Europe faces shortage of interest in modern program of
      public health education and research, and in mutual cooperation and cooperation
      with countries of European Union. In 2000, Stability Pact for Southeastern Europe
      has initiated a project: "Academic Programmes for Training and Research in Public
      Health in South Eastern Europe". The project named "Agreement on Collaboration of
      the Public Health Consortium for South Eastern Europe (PH-SEE) provides many
      opportunities to advance the cooperation and student exchange during post
      graduate studies. ACADEMIC PROGRAMMES FOR TRAINING AND RESEARCH IN PUBLIC HEALTH
      IN SOUTH EASTERN EUROPE: Academic programs include education of how to use
      Internet material in regard to public health from relevant areas and select
      skilled coordinatiors. 10 appropriate curricula have been developed with many
      models and most can be expanded. AGREEMENT ON COLLABORATION OF THE PUBLIC HEALTH
      CONSORTIUM FOR SOUTH EASTERN EUROPE: This document has the objective of
      establishing a formal agreement between the members of the Network enabling
      cooperation and student exchange programs during postgraduate studies. It
      supports the mobility of postgraduate students in their scientific or practical
      work, awards student scholarships or acquiring diploma at foreign universities.
      Each member of this network will support progress in the frame of mutual research
      and identify program priorities based on unilateral and multilateral cooperation
      in public health. CONCLUSION: Work on the project "Academic Programmes for
      Training and Research in Public Health in South Eastern Europe" has to be
      considered continual, including some colleagues who have interest in preventive
      medicine and in other areas. Agreement on Collaboration offers younger
      generations an opportunity for scientific training. According to recently signed
      Bologna Declaration, we are free to create a school of public health, and it
      becomes also our obligation.

PMID- 15503793
TI  - [Current status and potential perspectives in classical radiotherapy technology].
AB  - INTRODUCTION AND POTENTIALS OF CLASSICAL RADIOTHERAPY: After purchase of
      radiotherapy equipment in 2003, classic radiation therapy in Serbia will reach
      the highest world level. In order to define the highest standards in radiation
      technology, we analyzed the current status and potential perspectives of
      radiation therapy. TECHNOLOGICAL LEVELS OF RADIOTHERAPY IN DEVELOPED COUNTRIES:
      An analysis of present situation in the USA, assumed as the most developed in the
      world, was done. Available data, collected in the last 3 years (equipment
      assortment, therapy modalities, workload and manpower) for 284 radiotherapy
      centers, out of potential 2050, were analyzed. Results were presented as crude
      percentage and matched to point current status. RESULTS OF ANALYSIS AND
      DISCUSSION: The analysis showed that CLINAC accelerators are the most popular
      (82.7%), as well as, ADAC (43.7%) and Focus (CMS) (27.4%) systems for therapy
      planning. Movement towards virtual simulation is evident (59.3%), although
      classic "simulation" is not fully eliminated from the radiotherapy chain. The
      most popular brachytherapy afterloader is Microselectron HDR (71%). About 64.4%
      centers use IMPAC communication/verification/record system that seems more open
      than Varis. All centers practice modern radiotherapy modalities and techniques
      (CPRT, IMRT, SRS/SRT, TBI, IORT, IVBHRT, HDR BHRT, etc.). CT and MRI availability
      is out of question, but PET is available in 3% of centers, however this
      percentage is rapidly growing. Up to 350 new patients per year are treated by one
      accelerator (about 35 pts. a day). Centers are relatively small and utilize 2-3
      accelerators on average. Average FTE staffing norm is 4 radiation oncologists, 2
      3 medical radiotherapy physicists, about 3 certified medical dosimetrists and
      about 6 radiotherapy technologists. TECHNOLOGICAL ASPECTS AND CONCLUSION: In the
      past 5 years relative stagnation in classic radiotherapy has been observed. In
      spite of substantial investments in technology and consequent improvements, as
      well as wide introduction of computers in radiotherapy, radiotherapy results have
      not changed significantly. Vendor developement strategies do not point that this
      trend will change in the next 5 years. On the other hand, wide introduction of
      the PET in each radiotherapy chain ring (diagnostics, planning, follow-up), could
      improve results (local and regional control, as well as quality of patients'
      life).

PMID- 15503794
TI  - [Insulin secretion: mechanisms of regulation].
AB  - REGULATION OF INSULIN SECRETION: Beta cells are unique endocrine cells. They
      respond positively, in terms of insulin secretion, not only to changes in the
      extracellular glucose concentration, but also to activators of the phospholipase
      C (cholecystokinin or acetylcholine), and to activators of adenylate cyclase
      (glucagon, glucagon-like peptide-1, or gastric inhibitory polypeptide). Major
      messengers which mediate glucose action for insulin release are Ca2+, adenosine
      triphosphate (ATP) and diacylglycerol (DAG). MAJOR PATHWAYS OF INSULIN RELEASE
      STIMULATION: There are four major pathways involved in stimulation of insulin
      release. The first pathway is KATP channel-dependent pathway in which increased
      blood glucose concentrations and increased b-cell metabolism result in a change
      in intracellular ATP/ADP ratio. This is a contributory factor in closure of ATP
      dependent K+ channels, depolarization of b-cell membrane, in increased voltage
      dependent L-type Ca2+ channel activity. Increased Ca2+ influx results in
      increased intracellular Ca2+ and stimulated insulin release. KATP channel
      independent pathway augments Ca(2+) -stimulated insulin secretion of KATP channel
      dependent pathway. Major potentiation of release results from hormonal and
      peptidergic activation of receptors linked to adenylyl cyclase. Adenylyl cyclase
      activity is stimulated by hormones such as vasoactive intestinal peptide (VIP),
      glucagon-like peptide-1 (GLP-1), and so on. These hormones, acting via G protein,
      stimulate adenylyl cyclase, thus causing a rise in cyclic adenosine monophosphate
      (cAMP) and activation of protein kinase A (PKA). Increased activity of PKA
      results in potentiation of insulin secretion.

PMID- 15503795
TI  - [Possible complications of erythropoietin therapy in patients with chronic renal
      failure].
AB  - INTRODUCTION: There have been many publications in the past 20 years about
      positive effects of human recombinant erythropoietin, which is used in treatment
      of anemia, especially in patients on dialysis. COMPLICATIONS: The most important
      complications in patients treated with erythropoietin include: hypertensive
      reactions; thrombosis of AV fistula in patients on hemodialysis and appearance of
      severe anemia as a part of Pure Red Cell Aplasia (PRCA). The first two
      complications were managed quite easily with adequate erythropoietin dosage, and
      slower establishment of normal hemoglobin kevel, hematocrit level and red blood
      cell count, (our "target" Hb varied between 100 and 110 g/dl). PURE RED CELL
      APLASIA (PRCA): Pure Red Cell Aplasia is a progressive, marked anemia with sudden
      appearance of significant loss or complete absence of erythrocyte precursor cells
      in normal bone marrow. In patients with end stage renal disease treated with
      erythropoietin PRCA appears in acute form as a consequence of production of
      neutralizing antibodies to erythropoietin. Time period between the beginning of
      erythropoietin therapy and appearance of PRCA is from 3 weeks to approximately 9
      months. SYMPTOMS AND SIGNS: PRCA is characterized by sudden appearance of anemia
      in patients who had a satisfactory response to erythropoietin therapy till that
      moment. In PRCA, anemia is normocytic, normochromic with normal survival of red
      blood cells, without deficit in components such as iron, folic acid or vitamin
      B12, low reticulocyte count, decrease in Hg and normal platelet count. DIAGNOSIS:
      Diagnosis is based on clinical data (marked anemia), bone marrow biopsy, which
      shows a lower number of precursor red blood cells and presence of antibodies
      against erythropoietin. Before PRCA is diagnosed, all other causes for
      erythropoietin resistance must be excluded. THERAPY: Therapy of PRCA is based on
      cessation of erythropoietin therapy (all kinds), and correction of anemia with
      blood transfusions. INCIDENCE: PRCA is very rare and occurs in less than 1:10.000
      patient-years in patients treated with erythropoietin, not lethal by itself and
      generally reversible. Till December 31, 2002. PRCA has been diagnosed in 142
      patients world wide. In Serbia and Montenegro till this moment there hasn't been
      a single case of this syndrome. PREVENTIVE MEASURES: Continuous follow-up of
      reticulocyte count is the first step. Although this is a very rare disease, most
      of European Societies of Nephrology made protocols that recommend only
      intravenous application of -epoetin. Considering this new situation, Nephrology
      Society of Serbia and Montenegro recommends that -epoetin should be given to
      patients on hemodialysis only intravenously, while subcutaneous application of 
      epoetin is recommended in patients before beginning the dialysis treatment and in
      patients on hemodialysis, or who had undergone kidney transplantation.

PMID- 15503796
TI  - [Fistulas in gynecologic and obstetric surgical procedures].
AB  - INTRODUCTION: The study pointed to the significance and most frequent causes of
      development of fistula following gynecologic and obstetric surgical procedures.
      PREVENTION AND MANAGEMENT OF FISTULAS: Some possibilities of prevention, i.e. the
      necessity of correct administration of surgical procedures have been described.
      The authors pointed to the imperative of knowing the structure of vesicovaginal
      region and administration of adequate surgical technique. They described surgical
      procedures in most frequent gynecologic operations in prevention of ureteral
      injuries. They have presented 25-year result of operative treatment of these
      patients and treatment of postoperative fistulas at the Department of Obstetrics
      and Gynecology in Novi Sad. In regard to the number of gynecologic operations in
      that period (23067), the incidence of fistulas was not high (43). CONCLUSION:
      During the last years, the incidence is constantly decreasing, due to application
      of appropriate surgical techniques, careful manipulation, and administration of
      up-to-date surgical materials.

PMID- 15503797
TI  - [The role of splenic implants in spleen injuries and postoperative immunity].
AB  - INTRODUCTION: Spleen preservation by autotransplantation is indicated in cases of
      injuries which result with conquassation or total devascularization of this
      organ. MATERIAL AND METHODS: Thirty dogs, experimental group, had multiple,
      devascularized spleen injuries and underwent splenectomy and splenic
      autotransplantation. The same number of animals were treated by primary
      splenectomy (control group). Seventy five days later, animals from both groups
      were exposed to pneumococcal sepsis--by intravenous inoculation of sublethal
      pneumococcal doses, in order to estimate the immunity of lienal implants and
      compare the mortality rate between these two groups. RESULTS: Positive
      hemoculture, as well as logarithmic increase of diplococci in blood samples was
      established in all 60 animals. Higher mortality rate and significantly higher
      pneumococcal growth was established in control, compared to experimental group.
      CONCLUSION: These results point to the important role of lienal implants in total
      immunity and advantage of autotransplantation compared to conventional
      splenectomy, in cases of most severe and nonreconstructibile spleen injuries.

PMID- 15503798
TI  - [Specific vestibular exercises in the treatment of vestibular neuritis].
AB  - INTRODUCTION: Vestibular neuritis rapidly damages unilateral vestibular
      periphery, inducing severe balance disorders. In most cases, such vestibular
      imbalance is gradually restored to within the normal level after clinical
      therapies. This successive clinical recovery occurs due to regeneration of
      vestibular periphery and/or accomplishment of central vestibular compensation.
      REHABILITATION: The program of vestibular rehabilitation presents a major
      achievement in the field of treatment of balance disorders. Vestibular
      compensation is associated with central sensory reintegration and bilaterally
      equalizes the vestibular tonus over a period of time. MATERIAL AND METHODS: In
      this retrospective study of a series of cases authors present their results in 58
      patients undergoing a program of vestibular rehabilitation. Patients were divided
      into two groups. Thirty patients were in group I, and 28 in group II. Specific
      vestibular exercises were conducted in group I, and non-specific exercises in
      group II. Analysis of effects of vestibular compensation was made due
      electronystagmography. RESULTS: Results were satisfactory in both groups of
      patients. Absence of spontaneous nystagmus was detected in 83.3% of patients in
      group I (specific vestibular exercises) and in 53.5% of patients in group II (non
      specific exercises), with an average treatment time of up to 2 months.
      Harmonization of pendular stimulation was detected in 83.3% and 60.7% of patients
      in groups I and II, respectively. CONCLUSION: Early physiotherapeutic vestibular
      rehabilitation supports the vestibular compensation mechanism. At the same time
      vestibular rehabilitation may prevent panic disorder caused by hyperventilation
      syndrome.

PMID- 15503799
TI  - [External genital abnormalities in male schoolchildren: an epidemiological
      study].
AB  - INTRODUCTION: External genital abnormalities represent the most common congenital
      anomalies. Proper, not delayed diagnosis and treatment of certain abnormalities
      (undescended testis, hypospadia, varicocele) is of great importance for future
      fertility potential of children. MATERIAL AND METHODS: An epidemiological study,
      that consisted of an urological checkup, was performed among school-aged boys in
      two elementary schools. Prevalence of external genital, and inguinal region was
      examined. RESULTS: A total of 1229 elementary school boys were examined. The
      incidence of external genital abnomalities was 27.8%. Certain anomalies were
      already surgically treated in 7.8% of boys. Phimosis wasfound in 66 patients
      (5,5%), which represents 26.6% of all abnomalities. DISCUSSION: In this study the
      incidence of undescended testis was 2.0%. Although it is similar to literature
      data, the fact that undescended testis was found in 25 boys older than 7 years
      (two of them 15 years old!) suggests that the primary health care is not
      satisfactory. The incidence of inguinal hernia and hydrocele varies according to
      different authors from 0.8-4.4% to 13.44%. In this study the incidence was 2.4%.
      Varicocele represents a developmental anomaly and the incidence is increasing
      with age. It is rare in boys up to 10 years of age, but the incidence of
      varicocele in boys aged 15 years (15.8%) reaches the level of incidence in adults
      (19.82%). The incidence of phimosis in this study was 5.5%. CONCLUSION: High
      incidence of external genital abnormalities in school aged boys suggests a need
      for further education of physicians in primary health care services as well as of
      parents.

PMID- 15503800
TI  - [Effects of nutrition in pregnancy on hematological parameters].
AB  - INTRODUCTION: Pregnancy is one of the most important periods in a woman's life. A
      daily caloric increase of 150 kcal throughout the first and 350 kcal during the
      second and third trimesters is recommended. There are also increased requirements
      for some nutritive components. The aim of this study was to explore nutritive
      risk factors which affect hematological parameters and thus pregnancy and labor.
      It tested the hypothesis that there was a positive correlation between obese and
      underweight pregnant women and their nutrition, on one side, and hematological
      disorders of pregnant women on the other side. MATERIAL AND METHODS: The sample
      included 92 overweight, 65 underweight and 95 normally nourished pregnant women
      (control group). Blood analysis was compared with the results of the
      questionnaire on weekly consumption of different food groups. RESULTS AND
      DISCUSSION: The incidence of anemia was very high in both nutritive risk groups,
      while the increased number of leukocytes was dominant in underweight pregnant
      women. Food questionnaire confirmed inadequate intake of nutritive components in
      risk groups. CONCLUSIONS: All these facts may have important repercussions on
      pregnancy and labor, and anemia is often associated with prematurity, low birth
      weight of infants, greater number of premature labors, as well as the increased
      perinatal mortality. This study has confirmed the hypothesis that well balanced
      nutrition is really very important for regular functioning of the whole body,
      especially in risk population such as pregnant women.

PMID- 15503801
TI  - [Clinical evaluation of fecal continence after posterior sagittal anorectoplasty
      in anorectal abnormalities].
AB  - INTRODUCTION: Posterior sagittal anorectoplasty (PSARP) was introduced in 1982,
      by Pena and de Vries, as a new surgical procedure for patients with anorectal
      malformations. It was supposed to provide better chance for normal fecal
      continence. MATERIAL AND METHODS: Between 1991 and 2000, 50 patients with
      anorectal abnormalities underwent PSARP. In 43 patients PSARP was primary
      operation and in 7 it was a secondary procedure. At the time of study patients
      were not younger than 3, and not older than 13 years. Patients and their parents
      were interviewed, and fecal continence was graded as follows: voluntary bowel
      contractions, soiling less than once a week, soiling more than once a week, daily
      soiling and constipation. RESULTS: Amongst patients who underwent primary
      surgical correction, 74% had voluntary bowel contractions. Babies with perineal
      fistula, rectal atresia and stenosis presented with best results in term of
      voluntary bowel contractions (100%), as with vestibular fistula, ten of eleven
      patients. Only 18% of patients (atresia without fistula, vestibular fistula and
      bulbourethral fistula) had soiling. Patients with perineal fistula and rectal
      atresia and stenosis 40% were totally continent (voluntary bowel movements
      without soiling). The most frequent sequel was constipation, which appeared in
      48%, without coincidence with frequency of soiling. The problem of constipation
      was surprisingly more frequent in patients with expected better prognosis in
      fecal continence. CONCLUSION: Although PSARP offers a good esthetic result, only
      two third of patients have voluntary bowel movements and in about half there
      exists a problem with constipation, with necessary further treatment.

PMID- 15503802
TI  - [False aneurysm following arthroscopic meniscectomy of the knee].
AB  - INTRODUCTION: Blood vessel injuries during arthroscopic knee surgeries are
      unusual and rare and comprise less than 1% of all arthroscopic complications.
      Between 1990 and 2004, at the Department of Orthopedic Surgery and Traumatology,
      Institute of Surgery, Novi Sad, 2100 arthroscopic knee surgeries were carried
      out. Only one case of false aneurysm of the geniculate lateral inferior artery
      was reported. CASE REPORT: A 35-year-old professional waiter injured his left
      knee while getting up from a kneeling position. He had a typical clinical rupture
      with an interior meniscus lesion. Knee arthroscopy with resection of the torn
      part of interior meniscus was performed. Seven days later, we observed a
      subcutaneous tumefaction, 2 cm in diameter, which was warm, pulsating and painful
      on palpation. It was located in the region of anterolateral portal. Angiography
      confirmed the existence of a false aneurysm of lateral geniculate inferior
      artery. Revision of the wound was performed on the exterior side of the knee. The
      hematoma was removed and the artery tied A month later, the patient fully
      recovered and returned to his professional activities. DISCUSSION: Only four
      injuries, that is false aneurysms of the exterior knee artery after knee
      arthroscopy, have been described so far. The possibility for this injury to occur
      lies in the fact the artery lies over and is parallel with the lateral knee joint
      line, at the very entrance of the anterolateral arthroscopic port. Since the
      latter is the most often used arthroscopic port to access the knee, the above
      injury is possible, but it does not minifest clinically. This complication is
      easily diagnosed by a pulsating tumefaction in the area of arthroscopic port and
      is confirmed by angiography. These rare blood vessel injuries, do not affect the
      usage of anterolateral arthroscopic procedure. If the injury does exist,,
      revision of the wound and artery ligature should be carried out, which does not
      affect the final treatment results.

PMID- 15503803
TI  - [Acquired amegakaryocytic thrombocytopenia: three case reports and a literature
      review].
AB  - INTRODUCTION: Acquired amegakaryocytic thrombocytopenia (AAT) is a rare disease
      characterized by thrombocytopenia due to selective reduction/absence of bone
      marrow (BM) megakaryocytes. In the BM culture isolated reduction of colony
      forming units-megakaryocyte (CFU-Mk) may occur. MATERIAL AND METHODS: BM
      aspirates and trephine biopsies were obtained from all patients and processed by
      routine methods. In vitro BM culture and cytogenetic analysis was performed in
      one patient. RESULTS: This article presents three patients with manifested signs
      of hemorrhagic syndrome due to severe thrombocytopenia caused by an
      absence/significant reduction of BM megakaryocytes. Existence of systemic or any
      other disease was excluded in all patients. BM culture of the second patient
      showed reduction of all hematopoietic progenitors. In the subsequent course of
      the disease in this patient, signs of dysplastic erythrocytic series and
      megakaryocytes were also noted, although there were no positive proofs of
      evolution into myelodysplastic syndrome. DISCUSSION: AAT is a disease of
      hematopoietic stem cells manifesting in a certain period as amegakaryocytic
      thrombocytopenia which subsequently may progress into aplastic anemia or
      myelodysplastic syndrome. Patients were treated with corticosteroids, lithium
      carbonate, androgens, vincristine, immunoglobulins, folic acid, platelet and
      erythrocyte transfusions along with plasma substitution. The first patient
      reacted positively to the therapy. In two other patients a minimal, short-term
      therapeutic effect was achieved, followed by improvement of hemorrhagic syndrome
      and an insignificant increase in platelet count. In one patient the treatment was
      stopped after 4 months and the other died of bleeding after 4 months. CONCLUSION:
      AAT is a rare disease with unpredictable course. This is a case report of three
      patients with AAT and different therapeutic effects.

PMID- 15503804
TI  - [Parasite similar to Dirofilaria spp. surgically removed from the mesenterium].

PMID- 15503805
TI  - A modern life. After decades of discrimination, poverty, and despair, American
      Indians can finally look toward a better future.

PMID- 15503806
TI  - The shame of a nation.

PMID- 15503807
TI  - Localisation of the vacuolar proton pump (V-H+ -ATPase) and carbonic anhydrase II
      in the human eccrine sweat gland.
AB  - The localisation of the vacuolar proton pump (V-H+ -ATPase) and the enzyme
      carbonic anhydrase II (CAII) was investigated in the human eccrine sweat gland
      employing standard immunohistochemical techniques after antigen retrieval using
      microwave heat treatment and high pressure. The high-pressure antigen retrieval
      unmasked the presence of V-H+ -ATPase in the clear cells of the secretory coil,
      with a distribution similar to that previously observed for CAII. However, the
      dark cells were unreactive to both antibodies. In addition, heat and high
      pressure antigen retrieval demonstrated the presence of CAII in the apical zone
      of luminal cells of the reabsorptive duct, a location not previously reported.
      The localisation of V-H+ -ATPase and CAII in the secretory coil clear cells
      suggests that the formation of HCO3- and H+ by carbonic anhydrase II and the
      transport of H+ by V-H+ -ATPase may play an role in sweat fluid secretion. Their
      presence at the apex of the duct cells indicates involvement in ductal ion
      reabsorption.

PMID- 15503808
TI  - Immunolocalization of protein 4.1B in the rat digestive system.
AB  - Protein 4.1 family proteins are thought to interact with membrane proteins and
      also membrane skeletons. In this study, immunohistochemical studies by light and
      electron microscopy were performed with a specific antibody against protein 4.1B.
      Specific protein 4.1B immunolabeling was observed in simple columnar epithelium
      in the adult rat large intestine, small intestine and stomach. Protein 4.1B
      immunolabeling was localized along the membranes facing the adjacent cells
      (lateral portion) and also facing the extracellular matrix (basal portion).
      Moreover, a spatial protein 4.1B expression gradient was observed along the crypt
      villus axis of the rat small and large intestinal epithelium: strong protein 4.1B
      expression was present within the villus, with the crypt showing barely any
      detectable protein 4.1B. The expression of protein 4.1B was not detected in the
      stratified squamous epithelium in the forestomach or the esophagus. By
      immunoelectron microscopy, the immunolabeling of the cells was observed to be
      restricted to the cytoplasmic side just beneath the plasma membrane, including
      the membranes adjacent to the next cells, except for the tight junctions. We
      conclude that the protein 4.1B expression pattern is related to the maturation of
      simple columnar epithelium in the rat digestive system, probably by the effect of
      adhesion.

PMID- 15503809
TI  - Ethanol increases the paracellular permeability of monolayers of CAPAN-1
      pancreatic duct cells.
AB  - When grown on permeable supports, pancreatic duct adenocarcinoma CAPAN-1 cells
      establish very high values of transepithelial resistance (TER). The addition of
      ethanol produced a dose-related, reversible drop in the TER of these cells,
      ranging from 15% (with 1% ethanol) to 65% (with 10% ethanol). The ethanol effect
      was rapid and reversible. The resistance decrease was associated with an increase
      in monolayer permeability to mannitol. No significant decrease in cell ATP was
      detected for ethanol concentrations lower than 7%. Confocal vertical sections of
      calcein-loaded monolayers of CAPAN-1 cells, grown on plasticware, showed a
      progressive deflation of domes detectable after 5 min of treatment with 2%
      ethanol. Incubation in an ethanol-free medium caused a progressive dome
      restoration. Immunocytochemical analysis of ethanol-treated cells indicated that
      ZO-1 and occludin exhibited clear cut distribution changes while the
      perijunctional actin pattern was slightly modified. Electron microscopy showed
      that a discrete intercellular space was detectable between adjacent ethanol
      treated cells but not between control cells. These data indicate that ethanol is
      a tight junction barrier opener in pancreatic duct cells.

PMID- 15503810
TI  - Methoxychlor-induced alterations in the histological expression of angiogenic
      factors in pituitary and uterus.
AB  - Within the reproductive system, oestrogenic stimulation of uterine and pituitary
      tissue typically causes a proliferative response accompanied by an angiogenic
      induction of new blood vessels from existing ones, thereby providing nutrients
      and oxygen to the growing tissue. The pro-oestrogenic pesticide methoxychlor
      (MXC), however, has shown a differential effect on proliferative activity. An
      increase in uterine growth is present, while the pituitary undergoes a decrease
      in size, even though the effect is accompanied by a characteristic oestrogen
      induced elevation in pituitary prolactin concentration. The focus of the current
      study was whether the observed differences in tissue growth between uterus and
      pituitary in response to MXC administration were paralleled by a corresponding
      disparity in the expression of those growth factors (members of the vascular
      endothelial growth factor (VEGF) and angiopoietin families and their receptors)
      that are involved in the angiogenic cascade. Ovariectomized adult Sprague-Dawley
      female rats were administered MXC (0-200 mg/kg, oral) for 1 or 3 weeks.
      Immunohistochemical staining of uteri and pituitaries was performed under
      strictly controlled conditions for VEGF and its receptor VEGFR2, Angiopoietin-1
      (Ang1) and angiopoietin-2 and their tyrosine kinase receptor Tie2, and platelet
      endothelial adhesion factor (as an index of vascularity). Image acquisition and
      densitometric assessments of staining intensity were conducted under blind
      conditions. The results showed uterine MXC-induced increases in the expression of
      VEGFR2 and Ang1, changes consistent with a normal proliferative response to
      oestrogenic stimulation. For VEGF, staining tended to be most pronounced in the
      stromal region, although there did not appear to be a progressive increase with
      dose. VEGFR2 expression showed significant dose-related trends in luminal and
      glandular epithelia by 1 week. Similar effects at 1 week were evident for Ang1 in
      glandular epithelium. In the anterior pituitary, a dose-related increase in VEGF
      was present for the 1 and 3 week treatments, and the number of pituitary vessels
      per unit area was also increased after 3 weeks. The effects indicate that even
      though the insecticide has not been found to cause an augmentation in pituitary
      growth, a dose-related rise in the expression of at least one principal
      angiogenic factor is present that may be associated with an increase in vascular
      density.

PMID- 15503811
TI  - Macrophages in the small intestinal muscularis externa of embryos, newborn and
      adult germ-free mice.
AB  - Previously, we demonstrated the presence of a constant and regularly distributed
      macrophage population of ramified cells in the intestinal muscle layers of
      smaller rodents. The function of these resident macrophages under normal
      conditions remains unknown. Histochemistry, immunohistochemistry and electron
      microscopy were applied to the muscularis externa of 15- and 17-day-old embryos,
      2-day-old mice, adult germ-free and conventional mice. Since lipopolysaccharides
      (LPS) activates macrophages and inflammation affects gut motility, LPS-treated
      mice were also included in the study. Two macrophage antibodies, F4/80 and 2F8
      were used to demonstrate the presence of macrophages in the muscle layers. The
      localization was confirmed by electron microscopy. In contrast to conventional
      adult mice, the muscle layers in embryos, newborn and germ-free adult mice were
      devoid of class II MHC antigen reactive cells. The acid phosphatase reaction and
      antibodies directed towards a lysosomal protein (Lamp-2) were used in order to
      verify other activation markers. None of these showed specific staining of the
      muscularis macrophages. Only LPS-treated adult mice showed iNOS-positive cells in
      whole mounts. We conclude that the characteristic organization and distribution
      of muscularis macrophages in adult mice are also present in embryos, newborn and
      germ-free mice and thus develop independently of foreign antigens. Further, these
      macrophages are truly resident and appear to have differential responses to
      exogene stimuli.

PMID- 15503812
TI  - Prospects of TAT-mediated protein therapy for fragile X syndrome.
AB  - Fragile X syndrome is due to the absence of the fragile X mental retardation
      protein (FMRP). Patients are mentally retarded and show physical as well as
      behavioural abnormalities. Loss of protein in the neurons results in changes of
      dendrite architecture, and impairment of the pruning process has been indicated.
      Apart from some minor differences, no severe morphological changes have been
      observed in the brain. Until now, no therapy is available for fragile X patients.
      Recently it has been reported, that a protein transduction domain (TAT) is able
      to deliver macromolecules into cells and even into the brain when fused to the
      protein in question. Upon production of a TAT-FMRP fusion protein in a
      baculovirus-expression system, we used immunohistochemistry to verify TAT
      mediated uptake of FMRP in fibroblasts. However, uptake efficiency and velocity
      was lower than expected. Neuronal uptake was highly inefficient and the fusion
      protein demonstrated toxicity.

PMID- 15503813
TI  - Investigation of different transcript quantitation tools for high-throughput
      mapping of brain gene expression using voxelation.
AB  - Voxelation is a new approach for genome scale acquisition of brain gene
      expression patterns. The method employs high-throughput analysis of spatially
      registered voxels (cubes) to create multiple volumetric images of brain gene
      expression, similar to those obtained from biomedical imaging systems. The
      spatial resolution of voxelation depends on voxel size, with smaller voxels
      giving higher resolution. An important question is the applicability of different
      transcript profiling tools for the various levels of resolution that can be
      employed. Here, we describe the use of three methods to analyze voxel transcript
      abundance: real-time PCR, microarray analysis and linear amplification coupled
      with microarrays. We show statistically significant concordance between real-time
      PCR and microarray analysis for the myelin basic protein gene in human brain
      specimens at differing levels of spatial resolution. In addition, we also
      demonstrate the feasibility of using linear amplification coupled with microarray
      analysis to create voxelation maps from the mouse brain at high resolution, 1
      microl. These data indicate the suitability of a number of transcript profiling
      tools for various levels of spatial resolution in voxelation.

PMID- 15503814
TI  - Optimal conditions for the retrieval of CD4 and CD8 antigens in formalin-fixed,
      paraffin-embedded tissues.
AB  - The effects of buffer, NaCl, EDTA, and urea on the retrieval of CD4 and CD8
      antigens in formaldehyde-fixed, paraffin-embedded tissues with a microwave
      pressure-cooker were evaluated. The optimal retrieval conditions were found to be
      borate buffer at pH 8 containing 1 mM NaCl and 1 mM EDTA. Urea was found to be
      less effective.

PMID- 15503815
TI  - Evaluation of antigen retrieval buffer systems.
AB  - The introduction of antigen retrieval (AR) techniques has dramatically improved
      the sensitivity of immunohistochemical detection of various antigens in formalin
      fixed, paraffin-embedded tissues. The microwave-heating and pressure-cooking
      procedures are the most effective AR methods reported to date. Although extensive
      efforts have been made to optimize AR procedures using these two methods,
      previous studies have not led to a standard protocol applicable to all antibodies
      derived from different clones. In this study we have investigated the optimal AR
      buffer conditions for 29 antibodies that are in common use for diagnostic
      purposes in hospitals worldwide. Borate (pH 8.0) and Tris buffer (pH 9.5) yielded
      the highest retrieved antigen immunoreactivity against most antibodies as
      compared to other buffers tested. In addition, the microwave pressure-cooking
      gave better results than microwave-heating alone. Therefore, borate (pH 8.0) or
      Tris (pH 9.5) buffer used in conjunction with the pressure-cooking procedure is
      strongly recommended for standard routine use.

PMID- 15503816
TI  - Quantification of the effects of resperine on gonadotroph expression in the
      pituitary of goldfish (Carassius auratus).
AB  - In many teleosts, the control of gonadotropin II (or luteinizing hormone)
      secretion is under the dual control of stimulatory and inhibitory neuroendocrine
      factors. The principal stimulating factor is gonadotropin-releasing hormone and
      the main inhibitor is dopamine. Inhibiting the activities of dopamine by
      antidopaminergic drugs potentiates the actions of exogenous gonadotropin
      releasing hormone analogs, resulting in a surge release of luteinizing hormone
      and ovulation and spawning in a number of different species. As the effects of
      blocking the inhibitory actions of dopamine on gonadotroph cytology have not been
      studied, goldfish were treated with 2, 4, 6 or 8 injections of reserpine (0.1
      mg/kg body weight), at 48 h intervals, and the numbers of gonadotrophic cells
      studied at 48 h following last injection. After two injections, the number of
      gonadotrophic cells increased by 189% over controls; after four injections the
      increase was 234%; after six injections the increase was 259% and after eight
      injections, 288%. The results suggest that dopamine has an inhibitory influence
      on the numbers of gonadotrophs.

PMID- 15503817
TI  - Differential distribution of elastic tissue in human natural skin and tissue
      engineered skin.
AB  - Tissue-engineered skins (TES), manufactured by epidermal and dermal equivalents,
      are now being used in biological, pharmacotoxicological and clinical
      applications. It is thus interesting to know to what extent artificial organs are
      similar to natural counterparts. Elastic fibres are important constituents of the
      extracellular matrix of natural skin (NS). The aim of our study was to
      investigate the possible occurrence and distribution of elastic tissue in a model
      of human TES using different histochemical techniques, including classical Orcein
      and Fuchsin-Resorcin methods and immunohistochemistry, at both light and electron
      microscopical levels. Immunoperoxidase and high resolution immunogold methods
      were used. In NS, classical staining techniques and elastin-immunohistochemistry
      revealed a well-organized network of elastic fibres. High resolution
      immunocytochemistry revealed an intense labelling in the amorphous component of
      elastic fibres. Fibres of different diameters were immunostained. In TES, no
      stained elastic fibres were observed using classical staining techniques, and the
      interpretation of immunoperoxidase observations was not clear-cut. In contrast,
      immunogold staining at the electron microscopical level provided specific
      labelling of elastin-like immunoreactive material in the dermal equivalent.
      However, ultrastructural immunocytochemistry revealed that elastic tissue
      organization in TES was poor compared to that in NS. This study demonstrates that
      elastic fibres are a component of the extracellular matrix in this model of TES
      and suggests that fibroblasts of the dermal equivalent are engaged in matrix
      secretion. Nevertheless, the level of extracellular matrix organization in TES is
      low compared to NS. Moreover, this study also suggests that different models of
      bilayered TES may differ with respect to extracellular matrix organization. These
      aspects should be considered when TES is used in biological and
      pharmacotoxicological studies. A better understanding of the factors influencing
      extracellular matrix formation in TES is necessary to achieve further development
      of skin generation in vitro.

PMID- 15503818
TI  - ADVIA Centaur HER-2/neu shows value in monitoring patients with metastatic breast
      cancer.
AB  - INTRODUCTION: The proteolytic breakdown product corresponding to the
      extracellular domain (ECD) of the HER-2/neu oncoprotein p185 is found in the
      circulation of healthy individuals and patients having cancers of epithelial
      origin. For the current evaluation we sought to determine the analytical
      performance as well as the clinical utility of the newly developed ADVIA Centaur
      HER-2/neu assay (Bayer HealthCare LLC, Diagnostics Division, Tarrytown, NY, USA)
      in monitoring patients with metastatic breast cancer during the course of disease
      and treatment and to compare the obtained results with those of CA 15-3. METHODS:
      The analytical performance (including precision, normal range, interfering
      substances, minimum detectable concentration, dilution recovery, spiking recovery
      and high-dose hook effect) were determined. HER-2/neu and CA 15-3 values were
      measured in retrospective samples obtained from 59 patients with metastatic
      breast cancer undergoing treatment over a 6-12 month period. Serial changes in
      serum HER-2/neu and CA 15-3 were correlated with changes in clinical status on a
      visit-to-visit basis. For each pair of serial measurements, changes of equal to
      or greater than, or less than 15% for HER-2/neu and 21% for CA 15-3 were
      considered to indicate progression or lack of progression, respectively. RESULTS:
      The ADVIA Centaur HER-2/neu assay demonstrated within-run imprecision and total
      imprecision ranging from 3.0-5.6% and from 3.2-5.7%, respectively. The upper
      limit of normal was 15.2 ng/mL (90% CI: 14.2-17.0 ng/mL). No significant
      interference (<5%) was seen with bilirubins, hemoglobin, triglycerides and
      cholesterol or therapeutic drugs commonly present in the sera of breast cancer
      patients. The minimum detectable concentration (analytical sensitivity) was found
      to be 0.5 ng/mL. The patient population in the clinical study included breast
      cancer patients who responded to therapy (stable, partial or complete response)
      or had disease progression. HER-2/neu levels showed a concordance of 78.1%
      (82/105 restaging time points) with the clinical course of disease, whereas CA 15
      3 levels showed a concordance of 76.2% (80/105 restaging time points). The
      concordance with clinical status increased to 85.7% (90/105 restaging time
      points) when both results were used in combination as a series test. CONCLUSIONS:
      The ADVIA Centaur HER-2/neu assay provides excellent analytical performance for
      serial testing of serum HER-2/neu levels. The clinical data demonstrate the
      usefulness of serum HER-2/neu in monitoring metastatic breast cancer patients
      during treatment. Furthermore, the results indicate that serum HER-2/neu and CA
      15-3 may be useful in identifying disease progression or therapeutic response in
      different subgroups of women with metastatic breast cancer.

PMID- 15503819
TI  - Therapeutic strategies to improve the efficacy of oxaliplatin in gastrointestinal
      tumors.
AB  - The pharmacological characteristics of oxaliplatin make it one of the better
      chemotherapeutics to be combined with novel molecular-targeted anticancer
      treatments for the therapy of gastrointestinal tumors. The purposes of this
      review article are to report the preliminary data of combined therapy of
      oxaliplatin with inhibitors of angiogenesis or epidermal growth factor receptor
      and to suggest novel oxaliplatin-based therapeutic strategies. It is hypothesized
      that well designed, personalized, molecular-based treatments may improve the
      efficacy of oxaliplatin for the treatment of colorectal, gastric and pancreatic
      cancer. It is mandatory to rationalize such an approach by adequate determination
      of predictive surrogate biomarkers of response related to the targets in each
      single tumor against which therapy is aimed, using standardized assays and
      quality control.

PMID- 15503820
TI  - Mismatch repair protein MSH2 expression and prognosis of colorectal cancer
      patients.
AB  - INTRODUCTION AND AIMS: The role of genetic factors in the etiology and prognosis
      of patients with sporadic colorectal cancer is controversial. We have therefore
      investigated the biological and clinicopathological influence of
      immunohistochemical MSH2 expression in colorectal cancer. PATIENTS AND METHODS: A
      total of 49 consecutive patients with unselected colorectal cancer operated on in
      our unit were included in the study. All tumors were resected and tumor specimens
      were evaluated for MSH2 expression. Clinicopathological data and patient survival
      were correlated with MSH2 staining. Uni- and multivariate analyses were
      performed. The minimum follow-up period was five years. RESULTS: Curative
      resection was performed in 34 patients (64.9%), 14 of whom subsequently relapsed.
      At the end of the overall follow-up 25 (51%) patients had died, 21 of cancer
      related causes. Twenty-eight patients (57.1%) were negative for MSH2 staining.
      Only vascular invasion was significantly correlated with MSH2 expression (lower
      median values; p=0.04). The overall median survival was 47.9 months (95% CI=27
      86.6%). Multivariate analysis of variables in relation to survival showed that T
      stage (p=0.001), N stage (p<0.001) and MSH2 expression (p=0.01) were independent
      factors for survival. CONCLUSIONS: Reduced MSH2 expression is frequent in
      unselected colorectal cancer patients. Only vascular invasion was correlated with
      MSH2 expression in this study. Survival was related to TN stage and MSH2
      staining.

PMID- 15503821
TI  - Can IL-2R alpha be a valuable marker along with CA 19-9 in the diagnosis of
      chronic pancreatitis and pancreatic cancer?
AB  - BACKGROUND: Pancreatic cancer is characterized initially by non-specific
      abdominal symptoms followed by rapid tumor progression. Although chronic
      pancreatitis is a benign disorder, it can be one of the causative factors of
      pancreatic cancer. The level of the tumor marker carbohydrate antigen 19-9 (CA 19
      9) in pancreatic cancer does not correlate with the stage of the neoplasm.
      Soluble interleukin 2 receptor (sIL-2R) is a cytokine that shows increased levels
      during some inflammatory processes and malignant disorders. AIM: Our aim in this
      study was to investigate whether sIL-2Ralpha levels can be used in association
      with CA 19-9 in the early diagnosis of pancreatic cancer and chronic
      pancreatitis. PATIENTS: Serum samples were obtained from the blood of 21
      pancreatic cancer patients without distant metastasis who were deemed inoperable,
      16 chronic pancreatitis patients and 20 normal volunteers. RESULTS: We did not
      find any significant differences in CA 19-9 levels between normal controls and
      patients with chronic pancreatitis. There was a significant difference in the
      levels between the control group and the pancreatic cancer group (p = 0.003) and
      between patients with chronic pancreatitis and those with pancreatic cancer (p =
      0.004). Although there was no significant difference in sIL-2Ralpha levels
      between the control group and the patient groups, we found a slight correlation
      between sIL-2Ralpha and CA 19-9 levels in the pancreatic cancer group (p = 0.003,
      r = 0.623) and a more marked correlation in the chronic pancreatitis group (p <
      0.01, r = 0.751). CONCLUSION: According to our results, sIL-2Ralpha alone is not
      a good candidate marker in the diagnosis of pancreatic cancer; it can, however,
      be used in association with CA 19-9 for this purpose.

PMID- 15503822
TI  - PAP modulations in Daudi cells and Molt-3 cells treated with etoposide are
      mutually associated with morphological evidence of apoptosis.
AB  - Daudi (B-cell line) and Molt-3 (T-cell line) cells provide a model for the study
      of apoptosis, the induction of which is often accompanied by concominant
      modulations of proteins involved in mRNA maturation. One of these proteins is
      poly(A) polymerase (PAP), which is responsible for mRNA cleavage and
      polyadenylation. A number of recent reports also suggest involvement of mRNA
      maturation and stability in the induction of specific pathways of cell apoptosis.
      In this study we identified PAP activity levels and isoform modulations in two
      different cell lines (Daudi and Molt-3) and related them to DNA fragmentation (a
      hallmark of apoptosis) and cell cycle phase specificity in terms of the temporal
      sequence of events and the time that elapsed between administration of the
      apoptosis inducer (the widely used anticancer drug etoposide) and the observed
      effects. Treatment of both cell lines with 20 microg/mL etoposide induced
      apoptosis after four hours in Molt-3 cells and only after 24 hours in Daudi
      cells, as revealed by two independent methods. In Daudi cells the PAP activity
      levels and isoforms were downregulated prior to deltapsim reduction, DNA
      fragmentation and the morphological changes of the nucleus, whereas in Molt-3
      cells no PAP activity and isoform modulations were observed prior to the early
      hallmarks of apoptosis.

PMID- 15503823
TI  - Antibody response after vaccination with antigen-pulsed dendritic cells.
AB  - Dendritic cells (DCs) are the most potent antigen-presenting cells of the immune
      system capable of initiating immune responses to antigens. It is also well
      documented that cancer patients often experience anergy against tumor antigens.
      In this study we selected the best protocol for inducing the production of
      antibodies against the HER2 oncoprotein using DCs to overcome anergy. Murine DCs
      were pulsed in vitro, using different protocols, with recombinant HER2 fused to a
      human Fc (in order to improve DC antigen uptake) and were used to vaccinate mice.
      The obtained results indicate that antigen-pulsed DCs can induce an antibody
      response and that adding CpG after antigen pulsing greatly increases anti-HER2
      antibody production.

PMID- 15503824
TI  - Shift in the balance between circulating thrombospondin-1 and vascular
      endothelial growth factor in cancer patients: relationship to platelet alpha
      granule content and primary activation.
AB  - Tumoral angiogenesis is regulated by the balance between factors that activate
      and inhibit angiogenesis. Elevated levels of activators have been associated with
      a poor prognosis in cancer patients, but little is known about the net balance
      between circulating activators and inhibitors in these patients. This study was
      designed to determine whether the balance between circulating concentrations of
      the angiogenesis inhibitor TSP-1 and the activator VEGF differs from that in
      healthy persons, and to shed light on the possible role of platelets in this
      balance. Twenty-five cancer patients and 18 healthy subjects were included. Serum
      and plasma concentrations of VEGF, TSP-1 and PF4 were measured by ELISA. Our
      results showed that in healthy subjects the balance between the TSP-1 and VEGF
      concentrations in serum and in serum minus plasma was twice to three times as
      high as in cancer patients (p < 0.05). The theoretical TSP-1 content per platelet
      was greater in healthy subjects than in patients (94 vs. 53.6 ng/mL, p < 0.05),
      and platelet activation (determined indirectly as the plasma concentration of
      PF4) was greater in cancer patients (129 vs. 48 IU/mL, p < 0.01). Platelet
      activation correlated significantly with serum concentration of TSP-1 (r = 0.470,
      p = 0.018) and showed a tendency toward correlation with plasma concentration of
      TSP-1 (r = 0.382, p = 0.059). Our findings show that the circulating TSP-1/VEGF
      balance is diminished in cancer patients. Platelet activation may play an
      important role in this decrease and may ultimately lead to increased angiogenic
      activity in these patients.

PMID- 15503825
TI  - Circulating levels of VEGF-A, VEGF-D and soluble VEGF-A receptor (sFIt-1) in
      human breast cancer.
AB  - As circulating levels of vascular endothelial growth factor (VEGF-A) are raised
      in malignancy, the aim of this study was to investigate whether similar changes
      occur in two related factors, VEGF-D and the soluble VEGF-A receptor FIt-1 (sFIt
      1). Circulating levels of VEGF-A, VEGF-D and sFIt-1 were determined by ELISA in
      51 patients with primary breast cancer and matched healthy controls. Results were
      correlated with clinicopathological data. Whilst there was a difference in VEGF-A
      levels between patient and control groups (p = 0.03), no such difference was
      observed for sFIt-1 or VEGF-D levels and there was no association between
      individual factors and the clinicopathological variables examined. However, there
      was a positive correlation between VEGF-A and sFIt-1 levels in both patient and
      control groups (p < 0.0001). In addition, the ratio of sFIt-1 to VEGF-A was
      significantly different between patients and controls (p < 0.0001) and was also
      associated with tumour size (p = 0.01) within the patient group. During tumour
      progression there is a change in the relative amounts of sFIt-1 and VEGF-A in the
      circulation. Measuring the sFIt-1:VEGF-A ratio may have more significance than
      VEGF-A alone and further studies are needed to determine whether the ratio is of
      use as a prognostic marker or as a means of monitoring response to anti
      angiogenic therapy in cancer.

PMID- 15503826
TI  - Transforming growth factor beta 1 serum levels in patients with preinvasive and
      invasive lesions of the breast.
AB  - Transforming growth factor beta (TGF-beta)1 is thought to be involved in breast
      carcinogenesis. TGF-beta1 acts in an antiproliferative manner in the early stages
      of breast carcinogenesis, but promotes tumor progression and metastases in the
      advanced stages of the disease. No data have been published on serum TGF-beta1 in
      breast cancer. We investigated TGF-beta1 serum levels in patients with breast
      cancer (n=135), ductal carcinoma in situ (DCIS) I to III (n=67) or fibroadenoma
      (n=35), and in healthy women (n=40) to determine its value as a differentiation
      marker between malignant, pre-invasive and benign diseases and as a predictive
      marker for metastatic spread. Median (range) TGF-beta1 serum levels in patients
      with breast cancer, DCIS I-III or benign breast lesions and in healthy women were
      48.8 (18-82.4) pg/mL, 45.3 (26.9-58.3) pg/mL, 47.2 (17.2-80.5) pg/mL and 51.6
      (30.9-65.1) pg/mL, respectively (p=0.2). In breast cancer patients TGF-beta1
      serum levels showed no statistically significant correlation with tumor stage,
      lymph node involvement, histological grade, estrogen receptor status and
      progesterone receptor status. Our data fail to indicate any correlation between
      serum TGF-beta1 levels and clinicopathological parameters of breast diseases.
      Serum TGF-beta1 levels do not provide clinical information in addition to
      established tumor markers.

PMID- 15503827
TI  - Expression and clinical significance of pepsinogen C in uveal melanomas.
AB  - PURPOSE: we investigated by immunohistochemistry the pepsinogen C (pepC)
      expression in uveal melanomas and analyzed the possible relationship to
      clinicopathological parameters and prognostic significance. METHODS: We studied
      22 patients who had undergone enucleation of the eyeball or local tumor resection
      for uveal melanoma. The specimens were immunostained for pepC on formalin-fixed,
      paraffin-embedded sections. Sex, age, tumor location, histological type, local
      invasion, postoperative treatment and metastasis were evaluated. RESULTS: Eleven
      tumors (50%) were positive for pepsinogen C. The percentage of pepC-positive
      tumors was significantly higher in uveal melanomas with scleral invasion than in
      those without scleral invasion (p < 0.01). PepC expression was significantly
      associated with a shortened overall survival (p < 0.05). CONCLUSIONS: Our results
      show that pepsinogen C may be expressed by uveal melanoma and suggest that this
      protein could be considered as a new, unfavorable prognostic factor in these
      tumors.

PMID- 15503828
TI  - Vitamin D receptor polymorphisms and prostate cancer risk in Brazilian men.
AB  - Vitamin D seems to be an important determinant of prostate cancer risk and
      inherited polymorphisms in the 3'untranslated region of the vitamin D receptor
      (VDR) gene have been associated with the risk and progression of prostate cancer
      in some populations. We therefore studied VDR gene polymorphisms, as detected by
      Apal and Taql restriction fragments, in multiethnic Brazilian men (165 patients
      and 200 controls) for association with prostate cancer risk and parameters of
      disease severity (serum PSA, Gleason score and tumor stage). No statistical
      correlations were found. The unique ethnical background of Brazilian subjects,
      characterized by an extensive racial mixture of European, African-American and
      Native American, might have blunted any ethnic-specific significance of VDR
      polymorphisms. Further investigations of the associations between VDR and other
      genetic or environmental factors are warranted.

PMID- 15503829
TI  - Evaluation of reactive oxygen metabolites in frozen serum samples. Effect of
      storage and repeated thawing.
AB  - Measuring the free radical activity in serum samples from prospective studies is
      the best way to investigate the association between oxidative stress and human
      diseases. Prospective studies require the analysis of serum samples that have
      often been stored for a long time. Our study was designed to determine the effect
      of storage at -30 degrees C and -80 degrees C for two years on free radical
      activity. We analyzed the free radical activity by measuring circulating
      hydroperoxides in a pool of sera at baseline and after one day, one week, one
      month and 25 months of storage, using a photometric method (d-ROMs test).
      Measurements were performed in aliquots thawed only once at each time point and
      in aliquots frozen and thawed repeatedly over the study period. After two years
      we observed a small but statistically significant 4% decrease in the
      hydroperoxide concentration, which was substantially unaffected by storage
      temperatures and repeated freeze-thaw cycles. We also carried out the d-ROMs test
      in sera from ten apparently healthy volunteers at 2, 8, 24, and 48 hours after
      collection and storage at 4 degrees C and did not observe any significant
      variation. In conclusion, the d-ROMs test is a simple method suitable to evaluate
      the free radical activity in frozen serum samples after long-term storage.

PMID- 15503830
TI  - Is the evaluation of the global quality of life determined by emotional status?
AB  - The present study investigated relationships between global QOL perceptions and
      well-being dimensions. Especially our goal was to evaluate the impact of
      generally recognised four broad dimensions of QOL (physical, functional, social
      and emotional well-being) on global QOL perceptions, additionally person's
      satisfaction with life achievements and economical situation were measured as
      well as social demographic variables. The subjects were a representative sample
      of Finns (n = 4613, from 25 to 65 years) of the FINRISK-97 study. Correlation
      coefficients and models of hierarchical regression indicated that physical,
      functional and social well-being as well as sociodemographic factors and
      satisfaction with life achievements are important factors of global QOL
      perceptions both among males and females. However percentages of variances
      explained with these measures were only moderately high, ranging from 1 to 10%.
      After measures of emotional well-being were entered into the models of
      hierarchical analyses of regression, variances explained grew dramatically over
      20%. The results of the study indicated that global QOL judgements are likely to
      be based on current emotional state.

PMID- 15503831
TI  - Relationship with God and the quality of life of prostate cancer survivors.
AB  - This study explored the role of relationship with God with respect to the quality
      of life of men with prostate cancer. Thirty-four men with prostate cancer
      completed questionnaires on demographic and illness factors, aspects of
      relationship with God (e.g., God image), nonreligious resources (e.g., optimism)
      and physical, social and emotion functioning. Results showed that relationship
      with God was a significant factor in the prediction of role, emotional and social
      functioning for these men after controlling for age, reported severity of
      treatment reactions and nonreligious resources. Notably, different aspects of
      relationship with God (e.g., causal attribution) evidenced different associations
      with functioning and the nonreligious resource of perceived health control. Such
      results suggest that relationship with God may function in a complex manner as a
      resource in coping with prostate cancer. Longitudinal research is needed to
      clarify the role of religious/spiritual resources in the short- and long-term
      quality of life of men with prostate cancer.

PMID- 15503832
TI  - Determinants of health-related quality of life in long-term survivors of
      Hodgkin's lymphoma.
AB  - In this study health-related quality of life (HRQL) in long-term survivors of
      Hodgkin's lymphoma (HL) was evaluated and the findings were analyzed using a
      conceptual model developed by Wilson and Cleary. A better understanding of the
      relationships between the variables explaining HRQL may improve care and
      rehabilitation of HL patients. The populations were long-term survivors of HL (n
      = 121) and a control group (n = 236). Participants were approached with one semi
      structured interview, an extended version of the Schedule for the Evaluation of
      Individual Quality of Life - Direct Weighting (SEIQoL-DW) and three standardized
      questionnaires: Hospital Anxiety and Depression (HAD) scale, Short Form 12 health
      survey questionnaire (SF-12) and Sense of Coherence (SOC) scale. No differences
      regarding the mean scores were found between the HL survivors and the controls
      except for the SF-12, where the patients considered themselves to be in poorer
      physical health than the controls (p < 0.01). Even though physical health was
      diminished, patients did not evaluate overall QoL worse compared to the controls.
      The major determinants of perception of general QoL were self-rated physical and
      mental health as well as SOC. The HRQL of persons who have survived a median of
      14 years with HL is similar to that of controls.

PMID- 15503833
TI  - Urinary incontinence in women under 65: quality of life, stress related to
      incontinence and patterns of seeking health care.
AB  - OBJECTIVE: We sought to describe quality of life, psychological stress and
      patterns of seeking health care (PSHC) among young and middle-aged women
      experiencing urinary stress incontinence (USI). Reasons and variables associated
      with delay in seeking care were also investigated. METHODS: A sample of 131
      patients, aged 22-65, filled out a questionnaire consisted of: SF-36, stress
      related to incontinence, patterns of seeking health care questionnaires and a 10
      cm visual analogue scale (VAS) measuring perceived suffering from USI (0
      indicating absence of suffering while 10 indicating most severe suffering).
      RESULTS: Scores on eight domains of SF-36 were lower, compared to 405 Israeli
      healthy women (p < 0.001). Forty-one percent reported impairment in performing
      work and other activities. Mean scores on the VAS was 5.04 (SD: 2.59), 30% marked
      7 cm and higher and 12.6% reported most severe suffering due to USI (scored 10
      cm). Psychological stress related to incontinence was higher among the younger
      women and those with severe impairment to sexual activity. The majority of the
      sample (74%) delayed seeking help for at least a year, 46% delayed it for 3
      years. Common reasons for delay were lack of time (36.3%), shame (15.7%) and fear
      of surgery (14.7%). Age, psychological stress, perceived suffering and social
      functioning (SF) were associated with patterns of seeking care. CONCLUSIONS: USI
      causes suffering and impaired quality of life among young women. Reluctance to
      seek help highlights the need to promote women's knowledge of treatment options
      and cure prospects.

PMID- 15503834
TI  - The population perspective on quality of life among Americans with diabetes.
AB  - Quality of life (QOL) among Americans with diabetes was compared to Americans
      without diabetes using the Behavioral Risk Factor Surveillance System for 1996
      through 2000. QOL was measured in terms of days in the last month of limited
      activity, poor physical health, poor mental health, pain, depression, stress,
      poor sleep, and high energy and perceived general health. Each of 42,154
      diabetics was matched with one non-diabetic (control) respondent on age, sex,
      race, and ethnicity. Additional statistical adjustments were made for socio
      economic status, marital status, and access to health care. Respondents with
      diabetes averaged more statistically adjusted impaired days than controls: 3.11
      days (SE = 0.07) for physical health, 0.92 (SE = 0.06) for mental health, 1.69
      (SE = 0.06) for limited activity, 1.86 (SE = 0.16) for pain, 1.14 (SE = 0.14) for
      depression, 1.11 (SE = 0.16) for stress, 1.47 (SE = 0.18) for inadequate rest or
      sleep, and 3.54 (SE = 0.21) fewer for high energy. General health was also lower.
      Diabetes compromised QOL a substantial proportion of time on every dimension
      tested. Across the board, lower education, being unable to work, unemployed, or
      retired and lacking funds to pay for needed medical care were associated with
      greater impairments among persons with diabetes.

PMID- 15503835
TI  - Health-related quality of life in coronary heart disease compared to norms in
      Spanish population.
AB  - AIM: To interpret health-related quality of life (HRQL) values better, it is
      appropriate to compare them with population norms that can serve as reference
      standards. This study compares the quality of life of patients who have suffered
      an acute episode of ischemic cardiopathy with population norms, as measured by
      the Spanish version of the SF-36. METHODS: 132 patients admitted to the
      Cardiology Department of a Spanish general hospital for an acute episode of
      ischemic cardiopathy were studied. HRQL was assessed using the SF-36
      questionnaire. To compare patient with population norms, raw and adjusted data
      were obtained and differences with population norms were analyzed by age and sex
      groups at the level of the 25th percentile (25% +/- CI 95%). RESULTS: Globally,
      differences between the patients and the general Spanish population were evident
      in all SF-36 dimensions except Physical Functioning, General Health and Mental
      Health. However, the largest differences were observed in the youngest coronary
      patients (<55 years old) were in all HRQL dimensions, except Vitality and Bodily
      Pain, the proportions of patients below the 25th percentile of the general
      population exceeded 25%. CONCLUSION: The comparison between HRQL in coronary
      patients and that in the general population confirms the impact of the disease
      especially in the youngest patients, and allows intervention to be directed
      towards the more vulnerable groups.

PMID- 15503836
TI  - Health-related quality of life in amyotrophic lateral sclerosis: determining a
      meaningful deterioration.
AB  - This paper uses the standard error of measurement (SEM) and the standard error of
      the difference (S(diff)) in relation to data on individuals with amyotrophic
      lateral sclerosis (ALS) to calculate the minimum change scores required by
      statistical criteria for each dimension of the Amyotrophic Lateral Sclerosis
      Assessment Questionnaire (ALSAQ-40). Data collected from a longitudinal study was
      used to evaluate the usefulness of SEM and S(diff) criteria and to compare these
      criteria with an anchor-based approach in determining meaningful change.
      Questionnaires were completed on two occasions, 3 months apart. 764
      questionnaires were returned. Questionnaires included the ALSAQ-40 and dimension
      specific transition items. The ALSAQ-40 is a disease specific health-related
      quality of life instrument for use in studies of patients with ALS or other motor
      neuron diseases. For all dimensions of the ALSAQ-40 the patterns of SEMs were
      similar over time. The results suggest that, for example, six points change on a
      0-100 transformed scoring of the physical mobility dimension may be considered on
      distributional grounds a minimum meaningful change. The demonstrated consistency
      of SEMs for the dimensions of the ALSAQ-40 is empirical evidence of the
      theoretically claimed advantage of this measure of sample independence, and
      supports use of this distributional approach to calculate meaningful change.

PMID- 15503837
TI  - The impact of visual impairment and use of eye services on health-related quality
      of life among the elderly in Taiwan: the Shihpai Eye Study.
AB  - To evaluate the effect of impaired vision on health-related quality of life
      (HRQoL), the authors administered the Medical Outcomes Survey Short-Form 36 (SF
      36) to the elderly in a metropolitan Taiwanese community and assessed their
      visual impairment status. A structured questionnaire was used for door-to-door
      data collection. Interviewers also collected information on demographics, medical
      history, and HRQoL. Those who were interviewed were invited to the study hospital
      for a detailed eye examination. An eye examination, including presenting visual
      acuity and best-corrected visual acuity, was conducted by ophthalmologists.
      Presenting visual acuity and best-corrected visual acuity were measured in the
      better eye. Impaired vision was defined as presenting visual acuity in the better
      seeing eye worse than 6/12 (or 20/40) and was used to evaluate the correlation to
      HRQoL. A total of 1361 subjects at least 65 years of age participated in both the
      interview and eye examination. Internal-consistency and test-retest reliability
      of the eight scales were high. Based on the separate multiple regression model,
      after controlling for all other covariates, subjects in contact with vision
      services offered by an ophthalmologist had more positive scores on general health
      perceptions (beta = 4.29; p < 0.001), vitality/energy (beta = 2.73; p < 0.001),
      and mental health (beta = 2.06; p = 0.01). Impaired vision was associated with
      significantly lower scores in physical functioning (beta = -3.62; p < 0.001) and
      social functioning scales (beta = -3.25; p = 0.015). The findings suggest that
      visual impairment is associated with lower quality of life and use of eye care
      services is associated with higher quality of life.

PMID- 15503838
TI  - Update on the family strain questionnaire: a tool for the general screening of
      caregiving-related problems.
AB  - BACKGROUND: The growing prevalence of chronic diseases and home-based treatments
      has led to the introduction of a large number of instruments for assessing the
      caregiving-related problems associated with specific diseases, but our Family
      Strain Questionnaire (FSQ) was designed to provide a basis for general screening
      and comparison regardless of the disease. We here describe the final validation
      of its psychometric characteristics. METHODS: The FSQ consists of a brief semi
      structured interview and 44 dichotomic items, and has now been administered to
      811 caregivers (285 were simultaneously administered other questionnaires
      assessing anxiety and depressive symptoms). After a factorial analysis confirmed
      the 5-factor structure identified in previous studies (emotional burden, problems
      in social involvement, need for knowledge about the disease, satisfaction with
      family relationships, and thoughts about death), we undertook correlation and
      reliability analyses, and a receiver operating characteristics curve analysis
      designed to determine the cut-off point for the emotional problems identified by
      the first factor. Finally, univariate ANOVA with Bonferroni's post-hoc test was
      used to compare the disease-specific scores. RESULTS: The validity and
      reliability of the FSQ is good, and its factorial structure refers to areas that
      are internationally considered as being of general importance. The semi
      structured interview collects information concerning the socio-economic status of
      caregivers and their convictions/interpretations concerning the diseases of their
      patients. CONCLUSIONS: The FSQ can be used as a single instrument for the general
      assessment of caregiving-related problems regardless of the reference disease.
      This makes it possible to reduce administration and analysis times, and compare
      the problems experienced by the caregivers of patients with different diseases.

PMID- 15503839
TI  - A review of subjective impact measures for use with children and adolescents with
      epilepsy.
AB  - PURPOSE: To evaluate measures of epilepsy-specific impact currently available for
      use with children and adolescents. The relative merits of the different measures
      are examined. METHOD: Four published epilepsy-specific impact measures, the
      Epilepsy and Learning Disabilities Quality of Life Scale (ELDQOL), the Health
      related Quality of Life in Children with Epilepsy (HRQoLCE); the Impact of
      Childhood Neurologic Disability Scale (ICND), the Quality of Life in Epilepsy
      Inventory for Adolescents (QOLIE-AD-48), and the Quality of Life for Children
      with Epilepsy (QOLCE) were reviewed. RESULTS: There exist several shortcomings
      with the available measures on various psychometric criteria with not one of the
      currently available measures reaching acceptable psychometric standards in terms
      of reliability and validity. Of note are the particular inadequacies in the
      validation of scale content; with there being no investigation of the existence
      of age or ability effects for the items in any of the questionnaires reviewed.
      CONCLUSION: There is a clear demand for a psychometrically robust measure of
      subjective impact of epilepsy for children and adolescents, which is applicable
      to a wide age and ability range. At present, the efforts of the Canadian
      Pediatric Epilepsy Network with the recent publication of a novel measure holds
      much promise for the future. It is advocated that further efforts are made to
      further establish the psychometric properties of these scales and for their
      integration within a comprehensive outcome model for use in the evaluation of
      clinical interventions.

PMID- 15503840
TI  - Revision and psychometric testing of the City of Hope Quality of Life-Ostomy
      Questionnaire.
AB  - PURPOSE: Ostomies may be performed for bowel or urinary diversion, and occur in
      both cancer and non-cancer patients. Impact on physical, psychological, social
      and spiritual well-being is not unexpected, but has been minimally described in
      the literature. The City of Hope Quality of Life (COH-QOL)-Ostomy Questionnaire
      is an adult patient self-report instrument designed to assess quality of life.
      This report focuses on the revision and psychometric testing of this
      questionnaire. PATIENTS AND METHODS: The revised COH-QOL-Ostomy Questionnaire
      involved in-depth patient interviews and expert panel review. The format
      consisted of a 13-item disease and demographic section, a 34-item forced-choice
      section, and a 41-item linear analogue scaled section. A mailed survey to
      California members of the United Ostomy Association resulted in a 62% response
      rate (n = 1513). Factor analysis was conducted to refine the instrument.
      Construct validity involved testing a number of hypotheses identifying
      contrasting groups. RESULTS: Factor analysis confirmed the conceptual framework.
      Reliability of subscales ranged from 0.77 to 0.90. The questionnaire
      discriminated between subpopulations with specific concerns. CONCLUSIONS:
      Overall, the analyses provide evidence for the validity and reliability of the
      COH-QOL-Ostomy Questionnaire as a comprehensive, multidimensional self-report
      questionnaire for measuring quality of life in patients with intestinal ostomies.

PMID- 15503841
TI  - Construct validity of the EQ-5D in low-income Chinese American primary care
      patients.
AB  - OBJECTIVES: Although the EQ-5D has been used with increasing frequency to measure
      health-related quality of life, to date, the measure's validity has not been
      examined in Chinese American immigrants. We evaluated the construct validity of
      the EQ-5D by testing its performance with respect to sociodemographic and
      clinical characteristics of the population and comparing responses on the EQ
      dimensions with the SF-36 subscales. METHODS: The study surveyed low-income
      Chinese patients attending a community health center in New York City's
      Chinatown. Participants received self-administered versions of the EQ-5D and SF
      36 and additional questions regarding demographic and clinical information.
      RESULTS: 856 patients were approached and data were collected from 523 patients
      (61%). Analysis of the EQ-5D responses by sociodemographic and clinical variables
      found significant differences among categories of age, gender, marital status,
      number of medical problems, self-rated health, and specific medical problems.
      Correlations between similar dimensions and subscale scores were stronger between
      the two measures than dissimilar ones. Patients without impairments on a given EQ
      dimension tended to have higher SF-36 subscale scores than patients reporting
      'any' impairment (i.e. some/moderate or severe). CONCLUSIONS: The results provide
      initial support for the construct validity of the EQ-5D in our sample. Further
      studies should compare the performance of the EQ-5D with other preference-based
      measures in Chinese persons and examine the valuations that both low-income and
      Chinese persons place on core aspects of health.

PMID- 15503842
TI  - The Liver Disease Symptom Index 2.0; validation of a disease-specific
      questionnaire.
AB  - The available liver disease-specific questionnaires do address severity of
      symptoms but hardly evaluate how patients experience these specific symptoms
      during daily activities. The Liver Disease Symptom Index 2.0 (LDSI) includes 18
      items that measure symptom severity and symptom hindrance in the past week. In a
      large survey (n = 1175) conducted in collaboration with the Dutch liver patient
      association, convergent and divergent construct validity and the surplus value of
      including symptom severity and symptom hindrance items in the LDSI were examined.
      The LDSI items showed expected convergent and divergent correlations with Short
      Form-36 (SF-36) and Multidimensional Fatigue Index-20 (MFI-20) scales.
      Correlations revealed only a slight to moderate overlap between LDSI items and SF
      36 and MFI-20 scales. The impact of symptom severity and symptom hindrance on
      generic health related quality of life (HRQoL) varied in a different way across
      liver patients, which indicated that symptom severity items and the symptom
      hindrance items measure different aspects of HRQoL. We conclude that the LDSI
      provides information complementary to the information given by the SF-36 and the
      MFI-20 and that it is psychometrically sound to include both symptom severity
      items and symptom hindrance items in the LDSI.

PMID- 15503843
TI  - Quality of life after myocardial infarction: translation and validation of the
      MacNew Questionnaire for a Dutch population.
AB  - A wide range of instruments have been used in health-related quality of life
      (HRQL) assessment of patients with coronary artery disease. The MacNew heart
      disease health-related quality of life questionnaire (MacNew) is a disease
      specific measure of HRQL, that has been found to have both good discriminative
      and evaluative properties. The objective of the present study was to translate
      the MacNew for a Dutch population, and assess its reliability and validity. Three
      hundred and thirty-nine cardiac patients, admitted to the hospital after a
      cardiac event, participated in the study. Questionnaires were filled out at
      baseline, at 3 months, and at 12 months. A clinically relevant three-factor
      solution, reflecting an emotional, physical, and social domain of HRQL, allowed
      us to explain 55% of variance. Angina pectoris was consistently found to be
      significantly associated with worse HRQL. The pattern of correlations between the
      subscales of the MacNew on the one hand, and between the subscales of the MacNew
      and two other, related questionnaires on the other hand, indicated only modest
      convergent and discriminant validity. The internal consistency was found to be
      fair to (very) good (ranging between 0.78 and 0.95). Finally, the Dutch MacNew
      was demonstrated to be substantially more responsive than two other instruments
      measuring physical and psychological well-being.

PMID- 15503844
TI  - Development and testing of the Japanese version of the migraine-specific quality
      of life instrument.
AB  - We developed and tested a version of the migraine-specific quality of life
      (MSQOL) instrument for use in Japan. The MSQOL was translated into Japanese,
      evaluated by physicians and nurses who has experienced migraine headaches,
      'backtranslated', approved by the author of the original version, and tested in
      70 out-patients with migraine. There were no ceiling or floor effects. All three
      subscales were found to be internally consistent: alpha > or = 0.76. The
      patients' scores were similar to those reported in the user's manual, with the
      exception of a difference of about 11 points on the Avoidance Behaviors subscale.
      Some correlations between MSQOL scores and SF-36 scores were statistically
      significant, although none exceeded 0.52. Linear associations between some
      measures of symptoms and some MSQOL scales were statistically significant, but
      those associations were consistent neither for the two kinds of symptom reports
      (severity and frequency) nor across all MSQOL subscales. Low MSQOL scores in
      early 1999 correlated with more return visits for medication and with greater
      amounts of triptan (anti-migraine) medication in 2001 and 2002. Overall, we
      interpret these results as indicating that, while they cannot be used as
      substitutes for reports of symptoms, scores on the Japanese version of the MSQOL
      can be used to assess the impact of migraine headaches on patients' lives.

PMID- 15503845
TI  - Can China overtake the U.S. in science?

PMID- 15503846
TI  - Prevalence of dental fluorosis in rural areas of Davangere, India.
AB  - OBJECTIVES: To assess the prevalence and severity of dental fluorosis and its
      relationship with fluoride levels in drinking water. DESIGN: Twelve villages with
      similar climate, diet, socioeconomic conditions and altitudes were selected from
      rural areas of Davangere district, Karnataka, India. The fluoride concentration
      in drinking water was estimated by the Ion Selective Electrode Method. Dean's
      Index was used to assess the dental fluorosis. Karl-Pearson coefficient for
      correlation and simple regression analysis were used to evaluate the association
      between the water fluoride levels and the community fluorosis index (CFI).
      RESULTS: The study group consisted of 1,131, 12-15-year-old school children. The
      fluoride levels in drinking water of selected villages were in the range of 0.22
      3.41ppm. A stepwise increase in the prevalence of dental fluorosis with
      corresponding increase in water fluoride content, 13.2% at 0.22ppm F to 100% at
      3.41 ppm F, was found. There was a significant positive linear correlation
      (r=0.99) between CFI and water fluoride level. CONCLUSION: Dental fluorosis is a
      major dental public health problem among children in Davangere district and is
      related to drinking water with 0.74ppm fluoride or above.

PMID- 15503847
TI  - Community based schoolchildren's oral health programmes, Kuwait 1985--1998.
AB  - AIM: To describe the development of children's oral health programmes in Kuwait
      and present selected results and expected outcomes based on specific markers. To
      provide a basis for choosing best outcomes to develop public health policy and
      implement future programmes. METHOD: Assessment of the health, structural, cost
      and benefit changes in the oral health sector that resulted from policy decisions
      and implementation through different approaches in the period 1986--1998.
      RESULTS: Analysis has provided a basis for selection of appropriate methodologies
      to be implemented in the country. CONCLUSIONS: The regional programme consisting
      of full immediate prevention coverage with fluoride lozenges, periodic fluoride
      rinses, multi-operator care teams, flexible and moveable equipment appears to
      have provided the best potential within the Kuwait context during this period.

PMID- 15503848
TI  - Demand and referral pattern for orthodontic care at University College Hospital,
      Ibadan, Nigeria.
AB  - OBJECTIVE: To assess the demand and pattern of referral for orthodontic services
      at University College Hospital, Ibadan, Nigeria. DESIGN: A 21-month prospective
      clinic-based study of consecutive orthodontic patients. SETTING AND SAMPLE
      POPULATION: The orthodontic clinic of University College Hospital, Ibadan,
      Nigeria. One hundred and seventy-eight (178) consecutive patients, consisting of
      79 (44.4%) males and 99 (55.6%) females with mean age of 16.21+/-7.81 years were
      studied. RESULTS: 80% of subjects were 20 years of age or younger, while less
      than 2% were over 40 years of age. More females sought orthodontic care than
      males. Over 43% of the patients needed removable orthodontic appliances while
      close to 17% required treatment with fixed appliances. Extractions of retained
      primary teeth and other grossly malpositioned teeth accounted for 9.6% while
      24.7% needed observation of occlusal developments before any treatment decisions
      could be made. Dentists were noted to be the main referrers of these patients,
      accounting for over 49% of the referrals, followed by 25.4% who were self
      referred, and 18.3% who attended under parental influence. CONCLUSION: More girls
      than boys demanded orthodontic care and dentists were the major referrers of
      orthodontic patients.

PMID- 15503849
TI  - Is the fluoride level in drinking water a gold standard for the control of dental
      caries?
AB  - AIM: To obtain baseline knowledge of levels of dental caries in 12-year-old
      children residing in areas with varying levels of fluoride in drinking water in
      Pakistan; and to observe a dose-response relationship between the prevalence of
      dental caries at different concentrations of fluoride in drinking water. METHOD:
      Clinical examination of children and analysis of samples of drinking water.
      RESULTS: The maximum reduction of caries in relation to fluoride levels in
      Pakistan was witnessed between the fluoride concentrations of 0.00-0.33ppm.
      CONCLUSIONS: There are no gold standards for setting up a universal optimal level
      of fluoride in drinking water and each country needs to determine the
      concentration of fluoride in their drinking water in accordance with its socio
      economic and climatic conditions, dietary and oral hygiene habits of its
      population, and local research to determine how much fluoride is beneficial in
      the control of caries.

PMID- 15503850
TI  - Degree of correlation between two periodontal indices in a rural Croatian
      population.
AB  - AIM: To compare the periodontal status of patients measured by two indices, the
      Community Periodontal Index (CPI) and the Loss of Attachment Index (LA). METHOD:
      The CPI and LA index scores were determined for a sample of 367 adult subjects
      (1,535 dentate sextants) aged 15-65 years from two rural areas in Croatia and
      analysed according to subject, sextant and jaw. RESULTS: Partial correlation
      between the CPI and LA indices was found. Cumulative for all age groups, sextants
      with a CPI code 0, 1 and 2 most often appeared with a LA 0-3mm. Shallow pocket
      sextants (4-5mm) in 64.04% also correlated with the loss of attachment values 4
      5mm. In deep pocket sextants (6-8 mm), a deviation from expectations was found as
      they appeared more often with a LA 9-11 mm designation (46.24%), rather than with
      an LA 6-8mm (34.41%) score. Very similar results were found between distribution
      per sextant, person and jaw in CPI codes 2, 3, 4 and cumulatively. CONCLUSION:
      CPI itself is not sufficient for periodontal status assessment, especially for
      the 35-44 years of age, and even more so for the 65+ group, also for the CPI code
      4 in all ages.

PMID- 15503851
TI  - Cariology in Japanese dental schools.
AB  - AIM: The aim of this study was to evaluate the teaching of cariology in Japanese
      dental schools. DESIGN: Postal questionnaires were sent to all Japanese dental
      schools. PARTICIPANTS: Twenty-five of the 29 Japanese dental schools (response
      rate: 86%). RESULTS: The results were in many areas similar to those reported
      from North America. The non-surgical approach to the management of primary caries
      predominated, but no schools used bacteriological tests in caries diagnosis and
      only one school recommended antibacterial treatment. Four of the 25 responding
      schools advocated the treatment of primary enamel lesions by surgical
      intervention while three awaited operative intervention until the lesions had
      reached the middle third of the dentine. Recommendation of fluoride treatment was
      less common than in North America. The use of electronic devices to diagnose
      occlusal caries lesions was more common than in North America, but 'explorer
      catch' was the most frequently used method to diagnose primary and secondary
      caries in dental schools in both regions. CONCLUSION: Research in cariology over
      the years has led to altered views on how and when to treat caries lesions. The
      interpretation of research findings and the transfer of knowledge by teachers in
      dental schools have an impact on the practice of operative dentistry, but the
      diversity in the teaching of cariology indicates that the interpretation and
      implementation of modern principles in the treatment of caries differ quite
      markedly in Japanese dental schools.

PMID- 15503852
TI  - Periodontal treatment needs of patients with renal disease receiving
      haemodialysis.
AB  - AIM/OBJECTIVE: The aim of this study was to perform periodontal assessment, using
      the CPITN index, on patients undergoing renal dialysis. METHODS: The periodontal
      conditions of 342 subjects undergoing renal dialysis from eight renal dialysis
      centres were examined using CPITN. Subjects were distributed into four age
      groups, 16-19, 20-34, 35-44 and > or =45 years. The study was conducted during a
      6-month period. All clinical examinations were performed by one examiner.
      RESULTS: There was a significant positive relationship between the CPITN scores
      and age (r=0.164, p=0.002) and dialysis duration (r = 0.240, p=0.000). There was
      no statistically significant difference between male and female patients
      (p>0.05). None of the age groups had healthy sextants. The 35-44 year-age group
      had a higher number of sextants with deep pockets (0.19) than the other age
      groups and edentulous sextants were the highest among the oldest age group
      (1.89). CONCLUSION: A very small portion of the renal dialysis population is
      affected by severe forms of periodontitis requiring complex periodontal
      treatment. However, all such patients should be given oral hygiene education as a
      priority.

PMID- 15503853
TI  - An in vivo study of the plaque control efficacy of Persica: a commercially
      available herbal mouthwash containing extracts of Salvadora persica.
AB  - AIM: This study compared the oral health efficacy of Persica mouthwash
      (containing an extract of Salvadora persica) with that of a placebo. DESIGN: In a
      double-blind, cross-over trial, participants were randomly allocated to use
      either the Persica mouthwash or a placebo for a three-week period. Plaque
      accumulation, gingival bleeding and the salivary concentrations of mutans
      streptococci (MS) were measured before and immediately following the experimental
      period. After an eight-week 'washout' period, the study was repeated with
      participants using the alternative mouthwash. PARTICIPANTS: Twenty-eight healthy
      students (aged between 18 and 42 years) volunteered to take part in this
      investigation. RESULTS: Compared with the pre-treatment values, both placebo and
      experimental groups demonstrated significantly reduced gingival bleeding (p <
      0.01). Plaque scores were not significantly reduced following use of either
      Persica or the placebo. However, the use of Persica, but not the placebo,
      resulted in significant reduction in the carriage of MS (p < 0.05). CONCLUSION:
      Use of Persica mouthwash resulted in improved gingival health and lower carriage
      rate of cariogenic bacteria when compared with the pre-treatment values. The
      placebo (vehicle control) also improved gingival health significantly. Neither
      the Persica nor the placebo reduced the accumulation of dental plaque.

PMID- 15503854
TI  - Frequency of food items consumed by young rural and urban African children-
      essential knowledge to provide dietary advice in caries prevention.
AB  - AIMS: To determine the variety and frequency of consumption of food items,
      including cariogenic items, among 4-24-month-old black South African children.
      SETTING AND PARTICIPANTS: A rural area of low socioeconomic status, Ndunakazi,
      KwaZulu/Natal Province [n=105]; two urban areas in Gauteng Province: Soweto (low
      to middle socioeconomic status) [n=100], and the northern suburbs of Johannesburg
      and Sandton (middle to upper socioeconomic status) [n=101]. METHODS: Dietary
      intake was assessed using a food frequency questionnaire and analysed using SAS.
      OUTCOME MEASURES: Weekly frequencies for: number of times each food item was
      recorded; total consumption for each food item for the combined group of children
      and the three individual geographical areas. Food items were ranked in descending
      order according to the combined group of children within five selected food
      groups (carbohydrates, sugars, fruit and vegetables, milk and milk products,
      other foods and snacks). Only individual area results were listed. RESULTS: The
      preferred foods and frequency of consumption of these foods were identified.
      Significant differences were found between rural and urban groups for most of the
      food items, but not between urban groups. Food items were 'flagged' according to
      their cariogenic potential. CONCLUSION: The study provided valuable new
      information suitable for adapting and developing dietary advice relevant to
      caries prevention in African children

PMID- 15503855
TI  - Hyaluronan catabolism: a new metabolic pathway.
AB  - A new pathway of intermediary metabolism is described involving the catabolism of
      hyaluronan. The cell surface hyaluronan receptor, CD44, two hyaluronidases, Hyal
      1 and Hyal-2, and two lysosomal enzymes, beta-glucuronidase and beta-N
      acetylglucosaminidase, are involved. This metabolic cascade begins in lipid raft
      invaginations at the cell membrane surface. Degradation of the high-molecular
      weight extracellular hyaluronan occurs in a series of discreet steps generating
      hyaluronan chains of decreasing sizes. The biological functions of the oligomers
      at each quantum step differ widely, from the space-filling, hydrating, anti
      angiogenic, immunosuppressive 10(4)-kDa extracellular polymer, to 20-kDa
      intermediate polymers that are highly angiogenic, immuno-stimulatory, and
      inflammatory. This is followed by degradation to small oligomers that can induce
      heat shock proteins and that are anti-apoptotic. The single sugar products,
      glucuronic acid and a glucosamine derivative are released from lysosomes to the
      cytoplasm, where they become available for other metabolic cycles. There are 15 g
      of hyaluronan in the 70-kg individual, of which 5 g are cycled daily through this
      pathway. Some of the steps in this catabolic cascade can be commandeered by
      cancer cells in the process of growth, invasion, and metastatic spread.

PMID- 15503856
TI  - Stimulation of quiescent cells by individual polypeptide growth factors is
      limited to one cell cycle.
AB  - Since little is known about the function of polypeptide growth factors as
      regulators of multiple cell cycles, we compared the ability of FGF1, PDGF-AB and
      serum to induce a second round of DNA synthesis in Swiss 3T3 cells previously
      exposed to either FGF1, PDGF-AB or serum during the first cell cycle using [14C]-
      and [3H]thymidine in a double labeling system to distinguish between the first
      and second cell cycles. Surprisingly, we observed that cells exposed to either
      FGF1 or PDGF-AB in the first cell cycle were unable to synthesize DNA in response
      to FGF1 or PDGF-AB in the second cell cycle; yet these cells responded well to
      serum as a second cycle mitogen. Interestingly, while cells exposed to either
      FGF1 or PDGF-AB in the second cycle displayed normal receptor-mediated signaling
      and expressed cyclin D and E, they, like senescent fibroblasts and endothelial
      cells, failed to express cyclin A, and the continuous exposure of cells to either
      FGF1 or PDGF-AB resulted in a decrease in the kinase activity of the cyclin
      E/cdk2 complex. In addition, an increased association of this complex was
      observed with p21 CIP in an FGF1-dependent manner as well as with p27 KIP in a
      PDGF-AB-dependent manner. Lastly, the downregulation of p21 expression using an
      antisense strategy was able to partially rescue the replicative response of Swiss
      3T3 cells to FGF1 in the second cycle. These data suggest that (i) FGF1 and PDGF
      AB may limit their mitogenic effect to a single cell cycle, (ii) entry into the
      second round of replication is serum dependent and (iii) the self-limiting nature
      of FGF1 and PDGF-AB correlates with the accumulation of the cdk inhibitors, p21
      and p27, respectively.

PMID- 15503857
TI  - Testis-specific human small heat shock protein HSPB9 is a cancer/testis antigen,
      and potentially interacts with the dynein subunit TCTEL1.
AB  - Searching EST databases for new members of the human small heat shock protein
      family, we recently identified HSPB9, which is expressed exclusively in testis as
      determined by Northern blotting (Kappe et al., Biochim. Biophys. Acta 1520, 1-6,
      2001). Here we confirm this testis-specific expression pattern by RT-PCR in a
      larger series of normal tissues. Interestingly, while screening HSPB9 ESTs, we
      also noted expression in tumours, which could be verified by RT-PCR. Protein
      expression of HSPB9 was also detected in normal human testis and various tumour
      samples using immunohistochemical staining. We thus conclude that HSPB9 belongs
      to the steadily growing number of cancer/testis antigens. To get a better
      understanding of the function of HSPB9, we performed a yeast two-hybrid screen to
      search for HSPB9-interacting proteins. TCTEL1, a light chain component of
      cytoplasmic and flagellar dynein, interacted in both the yeast two-hybrid system
      and in immunoprecipitation experiments with HSPB9. Additionally,
      immunohistochemical staining showed co-expression of HSPB9 and TCTEL1 in similar
      stages of spermatogenesis and in tumour cells. The possible functional
      significance of this interaction is discussed.

PMID- 15503858
TI  - The DHE cell line as a model for studying rat gastro-intestinal mucin expression:
      effects of dexamethasone.
AB  - The expression of mucin genes was evaluated in rat intestinal cell lines in order
      to establish an in vitro model for investigating the regulation of intestinal
      mucin expression in this species. Two rat intestinal cancer cell lines (DHE, LGA)
      and three nontumoral rat intestinal cell lines (IEC6, IEC17, IEC18) were
      screened. The mRNA expression of rMuc1, rMuc2, rMuc3, rMuc4, and rMuc5AC mucin
      genes was studied by semiquantitative RT-PCR, real-time RT-PCR and Northern-blot
      analysis. Results were correlated with immunohistochemical expression of rat
      gastric and intestinal mucin proteins, and secretion of glycoconjugates was
      examined by enzyme-linked lectin assay. We showed that mRNA of rMucl and rMuc2
      were constitutively expressed in all IEC cell populations but periodic acid
      Schiff staining of these cells did not reveal the presence of glycoproteins. DHE
      cells expressed rMuc1-5AC mRNA and LGA expressed the same mucins but the level of
      rMuc4 was much lower. Mucin mRNA expression also differed in relation with the
      length of cultivation. Immunocytochemical studies revealed the presence of
      gastric and intestinal mucins in the two tumoral cell lines. Functional
      experiments showed that bethanechol, A23187 and PMA stimulated release of
      glycoconjugates in DHE but not in LGA cells. Treatment of DHE cells with
      dexamethasone (10(-7) mol/l) enhanced rMuc2 mRNA but decreased rMuc1 and rMuc5AC
      mRNA. Real-time RT-PCR showed that the expression of rMuc1 and rMuc5AC genes was
      reduced by more than tenfold after 24 h. The increased expression of rMuc2 gene
      was confirmed by Northern blot analysis. In conclusion, DHE cells provide a
      valuable cellular model for research on rat mucin secretion and expression.

PMID- 15503859
TI  - Sequence, evolution and tissue expression patterns of an epidermal type I keratin
      from the shark Scyliorhinus stellaris.
AB  - From the shark Scyliorhinus stellaris we cloned and sequenced a cDNA encoding a
      novel type I keratin, termed SstK10. By MALDI-MS peptide mass fingerprinting of
      cytoskeletal proteins separated on polyacrylamide gels, we assigned SstK10 to a
      46-kDa protein which is the major epidermal type I ("IE") keratin in this fish
      and is specifically expressed in stratified epithelia. In a phylogenetic tree
      based on type I keratin sequences and with lamprey keratins applied as outgroup,
      SstK10 branches off in a rather basal position. This tree strongly supports the
      concept that teleost keratins and tetrapod keratins resulted from two independent
      gene radiation processes. The only exception is human K18 because its orthologs
      have been found in all jawed vertebrates (Gnathostomata) studied; in the tree,
      they form a common, most early branch, with the shark version, SstK18, in the
      most basal position. Thus, the sequences of SstK10 and SstK18 also favor the
      classical view of vertebrate evolution that considers the cartilaginous fishes as
      the most ancient living Gnathostomata. To determine the overall expression
      patterns of epidermal ("E") and simple epithelial ("S") keratins in this shark,
      we furthermore tested a panel of monoclonal anti-keratin antibodies by
      immunofluorescence microscopy of frozen tissue sections, and in immunoblots of
      cytoskeletal preparations, demonstrating that immunodetection of specific
      keratins is a convenient method to characterize epithelial tissues in shark.

PMID- 15503861
TI  - Editorial overview: the chemistry of biological processes.

PMID- 15503860
TI  - LIM kinase 1: evidence for a role in the regulation of intracellular vesicle
      trafficking of lysosomes and endosomes in human breast cancer cells.
AB  - LIM kinase (LIMK) plays a critical role in stimulus-induced remodeling of the
      actin cytoskeleton by linking signals from the Rho family GTPases to changes in
      cofilin activity. Recent studies have shown an important role for LIMK1 signaling
      in tumor cell invasion through regulating actin dynamics. In this study, we
      investigate the role of LIMK1 in intracellular vesicle trafficking of
      lysosomes/endosomes. We analyzed by confocal immunofluorescence microscopy the
      cellular distribution of lysosomal proteins and the endocytosis of an endocytic
      tracer, epidermal growth factor (EGF), in LIMK1-transfected cells. We found in
      these cells an abnormal dispersed translocation of lysosomes stained for LIMPII
      and cathepsin D throughout the cytoplasm. The small punctate structures that
      stained for these lysosomal proteins were redistributed to the periphery of the
      cell. Computational 3D-image analysis of confocal immunofluorescence micrographs
      further demonstrated that these vesicles did not colocalize with the transferrin
      receptor, an early endosomal marker. Furthermore, LIMPII-positive lysosomes did
      not colocalize with early endosomes labeled with endocytosed Texas red
      transferrin. These results indicate that there is no mixing between dispersed
      lysosomes and early endosomes in the LIMK1-transfected cells. Moreover, LIMK1
      overexpression resulted in a marked retardation in the receptor-mediated
      internalization of Texas red-labeled EGF in comparison with mock-transfected
      cells. At 30 min after internalization, most of the Texas red-EGF staining
      overlapped with LIMPII-positive late endosomes/lysosomes in mock-transfected
      cells, whereas in LIMK1 transfectants only a small fraction of internalized EGF
      colocalized with LIMPII-positive structures in the perinuclear region. Taken
      together, the findings presented in this paper suggest that LIMK1 has a role in
      regulating vesicle trafficking of lysosomes and endosomes in invasive tumor
      cells.

PMID- 15503863
TI  - Recent developments in the discovery of protein kinase inhibitors from the urea
      class.
AB  - With two compounds on the market (Gleevec and Iressa), and a number of drug
      candidates in late-stage clinical trials, small-molecule kinase inhibitors hold
      great potential as novel therapies for cancer and inflammatory disorders.
      Inhibitors from the urea class were first reported in 1996 and have emerged as an
      important compound class for medicinal chemists due to their unique binding mode
      and kinase inhibition profile. Currently, five members of this class are
      undergoing clinical trials, BIRB-796 (Boehringer Ingelheim Pharmaceuticals Inc),
      BAY-43-9006 (Bayer AG/Onyx Pharmaceuticals Inc), CP-547632 (Pfizer Inc), MLN-518
      (Millennium Pharmaceuticals Inc) and KRN-951 (Kirin Brewery Co Ltd). This review
      focuses on the most recent developments in the discovery of urea-based protein
      kinase inhibitors.

PMID- 15503862
TI  - Integrating mass spectrometry into membrane protein drug discovery.
AB  - Membrane proteins represent a valuable source of potential drug targets due to
      their intimate involvement in a wide variety of disease states, including
      diabetes, cancer and neurological disorders. Defining the proteome of these often
      rare amphipathic molecules can be accomplished by exploiting the highly accurate
      and sensitive nature of mass spectrometry (MS). Technical advances have enabled
      MS to become a valuable tool for detailed mechanistic investigations into
      membrane proteins of unknown and known structure. The transfer of MS-screening
      strategies that have already been successfully used to identify interactions
      between soluble proteins and potential ligands, should allow the identification
      of drug candidates for membrane proteins in the near future.

PMID- 15503864
TI  - Design strategies for protein kinase inhibitors.
AB  - Deregulation of protein kinases due to mutation or overexpression is a hallmark
      of several diseases, for example, cancer, diabetes, inflammation and
      cardiovascular disorders. Consequently, there has been a growing interest in the
      discovery of protein kinase inhibitors as novel drugs. Here, we focus on key
      milestones and advances in protein kinase inhibitor drug discovery over the last
      year, with an emphasis on novel strategies such as targeting of single and
      multiple binding sites, inactive conformations of kinases, allosteric sites,
      regulatory domains and heat shock proteins. We will highlight recent developments
      for specific inhibitors in clinical studies for growth factor receptors, non
      receptor tyrosine kinases and serine/threonine kinases.

PMID- 15503865
TI  - Structural relationships between the insulin receptor and epidermal growth factor
      receptor families and other proteins.
AB  - The insulin receptor (IR) and epidermal growth factor receptor (EGFR) families
      are closely related members of the receptor tyrosine kinase superfamily, and are
      among the more intensively studied proteins in biology. Deregulated signaling by
      the type-1 insulin-like growth factor receptor (IGF-1R) or members of the EGFR
      family has been implicated in the progression of a variety of cancers. These
      receptors have thus emerged as validated therapeutic targets for the development
      of antitumor agents. In this review, recent progress in the elucidation of the
      three-dimensional structures of the extracellular domains of both receptor
      families is discussed. While the IGF-1R provided the first description of the
      extracellular domains of these two receptor families, it is the EGFR family in
      which greatest progress has been achieved. Over the past year, the field has
      progressed from having a complete absence of X-ray crystal structures to having
      eight such structures; ErbB-2 alone or complexed with the two monoclonal
      antibodies pertuzumab (Genentech Inc/Roche Holdings AG/Chugai Pharmaceutical Co
      Ltd) and trastuzamab, ErbB-3 without a ligand, EGFR with a ligand bound in an
      unactivated monomeric conformation, and EGFR with either epidermal growth factor
      (EGF) or transforming growth factor-alpha (TGFalpha) in a 2:2 dimeric complex.
      This review will discuss these developments and the opportunities they provide
      for the design of new therapeutic agents targeting their extracellular domains.

PMID- 15503866
TI  - Structural insights into the conformational selectivity of STI-571 and related
      kinase inhibitors.
AB  - STI-571 (Gleevec) is a highly successful cancer drug due to its activity as an
      inhibitor of the Abelson cytoplasmic tyrosine kinase (Abl), which is
      constitutively active in a majority of patients with chronic myelogenous
      leukemia. STI-571 also inhibits two type III receptor tyrosine kinases, c-Kit and
      platelet-derived growth factor receptor, and functions by targeting inactive
      conformations of these kinases. This review focuses on recent developments in X
      ray co-crystal structure analyses of STI-571 bound to Abl and the c-Kit receptor
      tyrosine kinase domain, and also three other relevant kinase inhibitor co-crystal
      structures. The similar structural features of these inactive kinases suggest
      they will be useful for the successful drug discovery and development of specific
      and targeted gene-based cancer drugs.

PMID- 15503867
TI  - GPCR-GIP networks: a first step in the discovery of new therapeutic drugs?
AB  - G protein-coupled receptors (GPCRs) are transmembrane molecules that, on
      interaction with G proteins upon ligand binding, can associate with a large
      variety of transmembrane or soluble proteins, termed 'GPCR-interacting proteins'
      (GIPs). Some special transmembrane GIPs are themselves GPCRs that form homo- or
      heterodimers, while other transmembrane GIPs are ionic channels, ionotropic
      receptors and single transmembrane proteins that control GPCR pharmacology and
      trafficking. Most soluble GIPs interact with the C-termini of GPCRs and often
      physically link GPCRs to large protein networks, called 'receptosomes', that
      include ionic channels, protein kinases, small G proteins, cytoskeletal proteins
      and adhesion molecules. Here, we review the nature and functions of some of these
      networks, such as the glutamate and serotonin receptosomes, and focus on the fine
      tuning of GPCR signaling by GIPs. Finally, we discuss the possibilities for
      developing new therapeutic drugs capable of modulating GPCR signaling by
      disrupting or reinforcing specific GPCR-GIP interactions.

PMID- 15503868
TI  - Genetic approaches to unraveling G protein-coupled receptor biology.
AB  - Genetic approaches to validating G protein-coupled receptors (GPCRs) have proven
      to be a powerful research tool, especially knockout studies in rodents. To date,
      data related to in vivo function have been published on approximately half of the
      human rhodopsin-like family-1 GPCRs, which can be attributed to the use of mouse
      knockouts. It is likely that many currently unknown yet important therapeutic
      mechanisms will be uncovered through knockout screens in mice. One such recent
      discovery is the elucidation of the in vivo function of the GPCR GPR54 through
      mouse genetics, and its subsequent validation in human populations. Although
      previously unsuspected, GPR54 has been found to be a master-regulator of the
      hypothalamic-pituitary-gonadal axis.

PMID- 15503869
TI  - G protein-coupled receptors in hypothalamic circuits involved in metabolic
      diseases.
AB  - G protein-coupled receptors (GPCRs) are cellular surface proteins that span seven
      transmembrane domains and constitute the largest family of receptors in the
      genome. They are highly expressed in the central nervous system, and particularly
      in the hypothalamus, a structure known to be involved in the regulation of energy
      balance. This review describes the cellular distribution of GPCRs within
      hypothalamic regions involved in the control of energy balance, and their
      signaling pathways. An approach which uses knowledge of these features might help
      to identify and prioritize targets for drug development and strengthen our
      understanding of the neurobiology of eating disorders.

PMID- 15503870
TI  - Analysis of human GPCRs in fission yeast.
AB  - G protein-coupled receptors (GPCRs) regulate diverse biological processes in all
      eukaryotes, including yeast, insects, plants and humans. This evolutionary
      conservation allows an almost unrestricted interchange of signaling components
      between different cell types. A large number of model systems have been developed
      for the study of GPCRs, and yeasts provide one of the more attractive hosts since
      they are amenable to both genetic and biochemical manipulation, while their
      robustness, low cost and lack of endogenous GPCRs are ideal starting points for
      the development of assays suitable for high-throughput screening. The purpose of
      this review is to introduce readers to the possibilities of using the fission
      yeast Schizosaccharomyces pombe for analysis of GPCRs. We describe the endogenous
      signaling pathways, the development of assays for heterologous GPCRs, and some of
      the technology available to elucidate GPCR structure and activity.

PMID- 15503871
TI  - Therapeutic opportunities for liver X receptor modulators.
AB  - The liver X receptors (LXRs), LXRalpha and LXRbeta, are ligand-activated
      transcription factors of the nuclear receptor superfamily that control the
      expression of genes involved in cholesterol and fatty acid metabolism. While the
      identification of small-molecule non-steroidal LXR agonists has validated the
      LXRs as potential drug targets for cardiovascular disease, recent reports from
      several research groups suggest that LXR ligands will be valuable therapeutic
      agents for the treatment of inflammation, diabetes and neurodegenerative
      diseases. This review focuses on the effects of LXR agonists on relevant
      signaling pathways, the recently reported ligand-bound LXR crystal structures,
      and recently disclosed LXR small-molecule templates.

PMID- 15503872
TI  - Molecular genetic probing of dopamine receptors in drug addiction.
AB  - Drug addiction is a brain disease with complex genetic, psychological and social
      factors. The dopaminergic system of the brain plays a central role in natural
      reward and motivation and is the main neural substrate for the actions of abusive
      drugs. The analysis of mice with mutations in their dopamine receptor genes has
      provided new information regarding the influence of individual dopamine receptors
      on drug actions. The use of genetic manipulation of dopamine receptors, and
      related intracellular signaling molecules, in mice will help to enhance our
      understanding of the molecular and cellular mechanisms underlying compulsive drug
      seeking and drug-taking behaviors, reasons for relapse into drug addiction and
      persistent neuronal changes in response to repeated drug use. These studies will
      provide new insights for improved therapeutic strategies for the prevention and
      treatment of drug addiction.

PMID- 15503873
TI  - gamma-Secretase as a target for drug intervention in Alzheimer's disease.
AB  - gamma-Secretase is a critical enzyme involved in the production of amyloid-beta
      (Abeta) peptide, one of the main pathological hallmarks of Alzheimer's disease.
      gamma-Secretase cleaves the beta-amyloid precursor protein (betaAPP) at a
      position predicted to be within the membrane. In addition to betaAPP, gamma
      secretase cleaves a range of other substrates. Thus, a key question in the
      development of gamma-secretase inhibitors for preventing Abeta production is
      whether undesired mechanism-based side effects may result from inhibition of
      cleavage of other substrates, and if so whether a suitable window exists to
      reduce brain Abeta. In this review, progress in the development of small-molecule
      inhibitors will be described, and potential toxicity issues associated with the
      development of gamma-secretase inhibitors discussed.

PMID- 15503874
TI  - Drug-induced fibrosis: interference with the intracellular collagen degradation
      pathway.
AB  - Drug-induced fibrosis and overgrowth of the extracellular matrix are high
      prevalence lesions of the oral mucosa. Drugs, such as dilantin, cyclosporin A and
      nifedipine can cause the gum tissues to overgrow, thereby preventing normal
      mastication and promoting infection. The causes of these disorders are poorly
      understood but recent evidence suggests that a common pathway targeted by these
      three drugs is the regulation of the intracellular pathway of collagen
      degradation. In this review, recent data that implicate calcium deregulation of
      the critical actin-dependent binding step of collagen phagocytosis will be
      discussed. These new insights highlight the need for a greater choice of
      medications for the treatment of transplant rejection and epilepsy to reduce the
      side effect of gingival overgrowth.

PMID- 15503875
TI  - Randomized, double-blind, placebo-controlled trials: the gold standard?

PMID- 15503876
TI  - The physician who made medicine accountable.

PMID- 15503877
TI  - Rhode Island Department of Health Strategic Plan: 2004-2010.

PMID- 15503878
TI  - Rhode Island Department of Health Strategic Plan: 2004-2010. Goal 1: Healthy
      Rhode Island 2010.

PMID- 15503879
TI  - Rhode Island Department of Health Strategic Plan: 2004-2010. Goal 2: Public
      health emergencies.

PMID- 15503880
TI  - Rhode Island Department of Health Strategic Plan: 2004-2010. Goal 3: Public
      health data, science & information.

PMID- 15503881
TI  - Rhode Island Department of Health Strategic Plan: 2004-2010. Goal 4: Healthy
      homes & healthy communities.

PMID- 15503882
TI  - Rhode Island Department of Health Strategic Plan: 2004-2010. Goal 5: Healthy
      human development in Rhode Island communities: improving family and community
      health opportunities.

PMID- 15503883
TI  - Rhode Island Department of Health Strategic Plan: 2004-2010. Goal 6: Quality
      improvement and regulatory compliance.

PMID- 15503884
TI  - Rhode Island Department of Health Strategic Plan: 2004-2010. Goal 7: Assess and
      build public health capacity.

PMID- 15503885
TI  - Rhode Island Department of Health Strategic Plan: 2004-2010. Goal 8: Infectious
      disease.

PMID- 15503886
TI  - The Hubbly-Bubbly.

PMID- 15503887
TI  - Miriam Hospital morbidity and mortality conference, a case of chronic headaches.

PMID- 15503888
TI  - New broadly-endorsed advisory statement on anti-microbial prophylaxis surgery.

PMID- 15503889
TI  - Epidemiology of hospitalizations for sepsis in Rhode Island, 1990-2002.

PMID- 15503890
TI  - Point of view: changing fashions in psychiatry.

PMID- 15503891
TI  - The anxious words of psychiatry.

PMID- 15503892
TI  - Tabloids' MRSA tests found wanting.

PMID- 15503893
TI  - Stories are 'sensationalist' says scientist.

PMID- 15503894
TI  - Choice makes its entrance.

PMID- 15503895
TI  - Campaigning ideas. This supporting life.

PMID- 15503898
TI  - Clinical management where medicine meets management. Array of hope.
AB  - Routine use of genetic profiling for managing some cancers could soon be a
      reality. Its wider application in cancer care will require substantial public
      investment in research and development, IT and setting up a service
      infrastructure. The first commercial test kits for breast cancer prognosis have
      already been launched in Europe and the US.

PMID- 15503899
TI  - Patient-public involvement. Can we build it?
AB  - The Royal Liverpool Children's trust is determined to move on after the organ
      retention scandal. New forums for parents, staff, carers and children have been
      set up. A newly formed communications team stresses openness and transparency.

PMID- 15503900
TI  - My brilliant career--mental health services director. Cycle of recovery.
      Interview by Nick Edwards.

PMID- 15503901
TI  - Law. A question of sex appeal.

PMID- 15503902
TI  - Buildings. The space age.

PMID- 15503903
TI  - Buildings. Bidding farewell.

PMID- 15503904
TI  - Buildings. Consuming passion.

PMID- 15503905
TI  - Buildings. Now we are 10.

PMID- 15503906
TI  - Stress urinary incontinence--a hidden condition.

PMID- 15503907
TI  - A review of the role of primary care in the diagnosis and management of stress
      urinary incontinence.
AB  - Women and men need to be informed that help for many urinary complaints is
      available and that treatment is effective. Workers in primary care should be
      encouraged to elicit urinary complaints from females because 'If doctors don't
      ask, patients don't tell'. All those in primary care who deal with patients with
      urinary disorders need to be sensitive to the great emotional and social distress
      associated with these complaints.

PMID- 15503908
TI  - The secondary care perspective.

PMID- 15503909
TI  - The costs of stress urinary incontinence.
AB  - SUI affects individuals' quality of life. It also has resource implications for
      individuals, health services and society in general. Quantification of these
      costs can aid decision making by illustrating the size of the problem and
      identifying conditions and groups for whom large costs are incurred. However,
      comparatively little is known about these costs as few costing studies have been
      carried out in the UK and no studies have identified costs by types of urinary
      incontinence.

PMID- 15503910
TI  - The future of SUI management ... a shift in emphasis?

PMID- 15503911
TI  - What do nursing and the law have in common: retention.

PMID- 15503913
TI  - Patient safety culture and leadership within Canada's Academic Health Science
      Centres: towards the development of a collaborative position paper.
AB  - Currently, the Academy of Canadian Executive Nurses (ACEN) is working with the
      Association of Canadian Academic Healthcare Organizations (ACAHO) to develop a
      joint position paper on patient safety cultures and leadership within Academic
      Health Science Centres (AHSCs). Pressures to improve patient safety within our
      healthcare system are gaining momentum daily. Because AHSCs in Canada are the key
      organizations that are positioned regionally and nationally, where service
      delivery is the platform for the education of future healthcare providers, and
      where the development of new knowledge and innovation through research occurs,
      leadership for patient safety logically must emanate from them. As a primer, ACEN
      provides an overview of current patient safety initiatives in AHSCs to date. In
      addition, the following six key areas for action are identified to ensure that
      AHSCs continue to be leaders in delivering quality, safe healthcare in Canada.
      These include: (1) strategic orientation to safety culture and quality
      improvement, (2) open and transparent disclosure policies, (3) health human
      resources integral to ensuring patient safety practices, (4) effective linkages
      between AHSCs and academic institutions, (5) national patient safety
      accountability initiatives and (6) collaborative team practice.

PMID- 15503914
TI  - Five Cs of leadership.

PMID- 15503915
TI  - Unintended consequences: two critical events from the 1960s and '70s and their
      legacy for nursing in Ontario.
AB  - In the late 1960s and early '70s, two key events occurred in Ontario that greatly
      affected the nursing profession: the unionization of the workforce and the move
      of diploma-granting nursing schools out of the hospitals (first to regional
      schools, then to the community colleges). At the same time, university nursing
      programs were undergoing significant changes. A paradigm shift occurred in which
      baccalaureate-prepared nurses were being educated for practice as well as for
      roles in education and administration. While all these activities had overall
      positive implications, there were unintended effects that continue to influence
      the profession today. These include the detachment of employers from clinical
      nursing education; fragmentation of the profession between front-line staff and
      the professional elites (proletarianization); rejection by front-line
      practitioners and college educators of nursing scholarship in favour of
      experiential and technical knowledge; and rivalry between college and university
      educators that has hampered the development of effective collaborations. For this
      study, interviews were undertaken with three informants, and their recollections
      were considered in the context of documentation from the College of Nurses of
      Ontario (the regulatory body), the Ontario Nurses Association (the union) and the
      Registered Nurses Association of Ontario (the professional association).

PMID- 15503916
TI  - Commentary: Education, patient care and employment are inextricably linked.

PMID- 15503917
TI  - An Elder-Friendly Hospital: translating a dream into reality.
AB  - The complex health profile of an older adult entering a hospital presents staff
      and administrators with a new challenge. This paper documents the Vancouver
      Island Health Authority's (VIHA) move towards an Elder-Friendly Hospital (EFH). A
      new approach to hospital care is described, one that takes account not only of an
      acute healthcare crisis, but also the developmental phenomena associated with
      aging, with the likelihood of chronic illnesses compounding both diagnosis and
      treatment. Customized strategies and suggestions for implementation that may be
      useful to other healthcare agencies are explained.

PMID- 15503918
TI  - Commentary: a call to think differently.

PMID- 15503919
TI  - Exploring ethical perspectives of nurses and nurse managers.
AB  - With nursing shortages reaching crisis proportions, staff nurses need to believe
      that nurse managers are supportive. However, evidence exists that staff nurses
      view nurse managers as moving away from basic nursing values. Using an
      exploratory philosophical approach, the authors examine this issue as a function
      of differing ethical frameworks used by nurses and nurse managers. The main
      question is whether nurse managers are expected to subscribe to a corporate ethic
      versus a nursing ethic in making decisions, and whether these approaches are
      fundamentally different. The authors' supposition was that exposing differences
      might account for some dissatisfaction that nurses express with regard to nursing
      leadership. They conclude that there are differences of emphasis in ethical
      principles that may cause tension. Incongruencies between corporate and
      individual values emerge under fiscal constraints and with differing perceptions,
      expectations and decision-making criteria. This paper offers suggestions to help
      staff nurses and nurse managers reduce tensions experienced when difficult
      choices, particularly those of resource allocation, are required.

PMID- 15503920
TI  - Maximizing the involvement of rural nurses in policy.
AB  - Rural health issues are increasingly recognized as needing attention, but many
      health policies in Canada are developed for the urban context and universally
      applied to rural settings. Addressing rural nurses' opportunities for involvement
      in policy will contribute to our general understanding of rural health while
      improving community health services. Rural nurses are in a unique position to
      assist because of their intimate knowledge of their communities and their
      position as informal community leaders. Challenges to their involvement include
      decreased numbers and lack of educational preparation about policy. A strength is
      the higher percentage of rural nurses who are managers compared to their urban
      counterparts. Nursing education programs need to include theoretical content and
      practical opportunities related to health policy. Managers need to support rural
      nurses' attempts in policy development by providing opportunities for membership
      on policy committees. Finally, once obtaining skills in the policy arena, rural
      nurses need to work within their communities and workplaces to help develop and
      implement more appropriate rural-based policies.

PMID- 15503921
TI  - University nurse graduates: perspectives on factors of retention and mobility.
AB  - This descriptive study explored the perspectives of 51 university nurse graduates
      from the St. Francis Xavier University School of Nursing. Qualitative and
      quantitative data were collected using telephone interviews to study a range of
      variables including geographic mobility patterns, career satisfaction and
      attitudes towards recruitment and retention factors. Given the negative
      perceptions in the media about nursing, the results of the study were unexpected
      and offer a sense of hope to those considering nursing as a career. Results
      indicate that graduates remained enthusiastic about their career choice and would
      choose nursing again as a career given the opportunity to do so. Furthermore,
      they would recommend nursing to others as a desirable career. The majority of
      graduates entered nursing because of a desire to make a meaningful difference in
      people's lives, and they were strongly influenced by positive nurse role models.
      Participants remained committed to a career in nursing, enjoyed considerable
      geographic mobility with migration to other Canadian provinces and the USA, but
      the majority returned to Canada for employment in nursing. The study confirms
      that the supportive nature of the work environment in which care is practised,
      the presence of visible and empowering nurse leaders, adequate compensation and
      benefits, and appropriate investment in continuing education and professional
      development of staff are significant factors in retaining nurses. Additional
      recommendations for enhanced recruitment and retention strategies are provided.

PMID- 15503922
TI  - Staff nurse empowerment and effort-reward imbalance.
AB  - The purpose of this study was to test an expanded model of Rosabeth Moss Kanter's
      Structural Theory of Organizational Behaviour (Kanter 1977; Laschinger, Finegan,
      Shamian and Wilk 2001) by examining the relationship between nurses' empowerment
      and their perceptions of effort-reward imbalance (Siegrist 1996). A sample of 112
      staff nurses employed in teaching hospitals in Ontario participated in this study
      (58% return rate). A descriptive correlational survey design was used to collect
      data by eLiciting responses to five self-report instruments: the Conditions of
      Work Effectiveness II, the Job Activities Scale II, and the Organizational
      Relationships Scale II (Laschinger, Finegan, Shamian and Wilk 2001), the Effort
      Reward Imbalance (ERI) scale (Siegrist and Peter 1999a) and a demographic
      questionnaire. Staff nurses were only moderately empowered, and 24.1% perceived
      their work to have more efforts than rewards, according to Siegrist's guidelines.

PMID- 15503923
TI  - Plasma-source mass spectrometry for speciation analysis: state-of-the-art.
AB  - Current and emerging capabilities of plasma-source mass spectrometry (PS-MS) as
      it is employed for elemental speciation analysis are reviewed. Fundamental
      concepts and their advantageous aspects, experimental conditions, and analytical
      performance are described and illustrated by recent examples from the literature.
      Novel instrumentation, techniques, and strategies for inductively-coupled plasma
      mass spectrometry (ICP-MS), microwave-induced plasma (MIP) mass spectrometry,
      glow-discharge (GD) mass spectrometry, and electrospray ionization (ESI), among
      others, are described. The use of ionization sources that provide tunable
      ionization, others that can be modulated between different sets of operating
      conditions, and others used in parallel is also examined.

PMID- 15503924
TI  - Element-selective detection in liquid and gas chromatography by diode laser
      absorption spectrometry.
AB  - An element-selective detector for chromatography based on atomic absorption
      spectrometry with semiconductor diode lasers is described. The analytical utility
      of the technique is demonstrated by speciation examples of HPLC and GC employing
      analytical flames and plasmas to atomize.

PMID- 15503925
TI  - State-of-the art of selective detection and identification of I-, Br-, Cl-, and F
      containing compounds in gas chromatography and liquid chromatography.
AB  - This review article presents an overview of halogen-specific detection in gas
      chromatography (GC) and liquid chromatography (LC). Attention is primarily
      focused on the use of plasma emission spectroscopy and plasma mass spectrometry
      as detectors, but other halogen-selective detection principles are also
      mentioned. Different instrumental configurations are discussed both with respect
      to technical set-up and performance, the principal reasons for halogen-selective
      detection are highlighted, and recent applications are reviewed from areas such
      as environmental chemistry, petroleum characterization, and drug analysis.

PMID- 15503926
TI  - Pulsed discharge detector: theory and applications.
AB  - The pulsed discharge detector (PDD) is a significant advancement in gas
      chromatography (GC) detector design which can be operated in three different
      modes: pulsed discharge helium ionization (He-PDPID), pulsed discharge electron
      capture (PDECD) and helium ionization emission (PDED). The He-PDPID can detect
      permanent gases, volatile inorganics and other compounds which give little or no
      response with the flame ionization detector (FID) and has significantly better
      limits of detection (minimum detectable quantities (MDQs) in low picogram range)
      than can be achieved with a thermal conductivity detector (typically not lower
      than 1 ng). The PDECD has similar or better sensitivity (MDQs of 10(-15) to 10(
      12) g) than radioactive source ECD but does not require licensing, wipe tests and
      other administrative or safety requirements which have increased over security
      concerns. The PDED shows promise as an extremely selective and sensitive
      elemental detector but a commercial unit is not presently available. In this
      report, the theory of operation, applications of the PDD and the practical
      aspects of using this novel detector are presented.

PMID- 15503927
TI  - Manganese speciation using capillary electrophoresis-ICP-mass spectrometry.
AB  - Manganese is a trace element known to activate many enzymes involved in metabolic
      processes and it shows protective function against oxidative stress. On the other
      hand, increased Mn levels are known for damaging the central nervous system,
      resulting in motoric abnormalities and psychic disorder. Such additional Mn
      exposure can cause an "Mn overflow" in the liver, accompanied by production of
      specific (labile) Mn transporters (Mn-species). The speciation of these Mn
      compounds is still unknown but they are believed targeting the brain. The aim of
      this paper was to develop a speciation method for manganese species in liver
      extracts, which allows to speciate the compounds quickly and with minimal risk of
      species alteration. Capillary electrophoresis (CE)-inductively coupled plasma
      mass spectrometry (ICP-MS) offers a valuable tool as analytes are not in contact
      to a stationary phase which probably affects species stability. Separation
      usually is fast and ICP-MS detection is element specific and sensitive. The paper
      describes the set-up and optimization of the hyphenated technique, optimization
      of separation according to pH and finally the Mn speciation of a liver extract.
      Several Mn species were found, such as arginase, Mn-transferrine, Mn-albumine and
      some more. The detection limit of the method was determined at 1.1 microg Mn/L
      independent on the species.

PMID- 15503928
TI  - Comprehensive two-dimensional gas chromatography coupled with fast sulphur
      chemiluminescence detection: implications of detector electronics.
AB  - Within the petrochemical industry, there has been a growing interest in methods
      capable of providing detailed information on the distribution of sulphur
      containing compounds in various product streams, going down to the level of
      separating and quantifying individual sulphur species. Since no single capillary
      gas chromatographic column is able to perform this separation, a refuge to multi
      dimensional separation techniques has to be taken. In this respect, comprehensive
      two-dimensional gas chromatography (GC x GC) coupled with sulphur
      chemiluminescence detection (SCD) has shown to be highly promising. It has been
      suggested, however, that the detector volume of an SCD restricts its potential to
      keep up with the fast second-dimension separations of contemporary GC x GC. In
      this paper, we will demonstrate that the lack of speed of the SCD does not
      originate from its physical dimensions, but is largely determined by the speed of
      the electronics used. Additionally, some typical examples will be presented to
      illustrate the potential of GC x GC coupled with fast SCD.

PMID- 15503929
TI  - Selective detection and identification of Se containing compounds--review and
      recent developments.
AB  - The complexity of selenium (Se) chemistry in the environment and in living
      organisms presents broad analytical challenges. The selective qualitative and
      quantitative determination of particular species of this element is vital in
      order to understand selenium's metabolism and significance in biology,
      toxicology, clinical chemistry and nutrition. This calls for state-of-the-art
      analytical techniques such as hyphenated methods that are reviewed with
      particular emphasis on interfaced separation with element-selective detection and
      identification of the detected selenium compounds. Atomic spectral element
      specific detection for monitoring chromatographic eluent enabled quantitative
      determination of selenium species in selenized yeast and qualitative measurement
      for breath samples. Gas chromatography with atomic emission detection (AED) of
      ethylated species and fluoroacid ion pair HPLC applied to the analysis of
      currently produced or archived selenized yeast and Brassica juncea have revealed
      the presence of a previously unrecognised Se-S amino acid, S
      (methylseleno)cysteine.

PMID- 15503930
TI  - Analysis of phosphorus herbicides by ion-pairing reversed-phase liquid
      chromatography coupled to inductively coupled plasma mass spectrometry with
      octapole reaction cell.
AB  - A reversed phase ion-pairing high performance liquid chromatographic (RPIP-HPLC)
      method is developed for the separation of two phosphorus herbicides, Glufosinate
      and Glyphosate as well as Aminomethylphosphonic acid (AMPA), the major metabolite
      of Glyphosate. Tetrabutylammonium hydroxide is used as the ion-pairing reagent in
      conjunction with an ammonium acetate/acetic acid buffering system at pH 4.7. An
      inductively coupled plasma mass spectrometer (ICP-MS) is coupled to the
      chromatographic system to detect the herbicides at m/z = 31P. Historically,
      phosphorus has been recognized as one of the elements difficult to analyze in
      argon plasma. This is due to its relatively high ionization potential (10.5 eV)
      as well as the inherent presence of the polyatomic interferences 14N16O1H+ and
      15N16O+ overlapping its only isotope at m/z = 31. An octapole reaction cell is
      utilized to minimize the isobaric polyatomic interferences and to obtain the
      highest signal-to-background ratio. Detection limits were found to be in the low
      ppt range (25-32 ng/l). The developed method is successfully applied to the
      analysis of water samples collected from the Ohio River and spiked with a
      standard compounds at a level of 20 microg/l.

PMID- 15503931
TI  - Germanium dioxide as internal standard for simplified trace determination of
      bromate, bromide, iodate and iodide by on-line coupling ion chromatography
      inductively coupled plasma mass spectrometry.
AB  - The use of elemental mass spectrometry as detection for ion chromatography allows
      sensitive determination of several bromine and iodine species at a reasonable
      time scale. Lowest concentrations observable are 66 ng L(-1) for bromate, 45 ng
      L(-1) for iodate, 74 ng L(-1) for bromide and 151 ng L(-1) for iodide. A major
      drawback of previous IC-ICP-MS applications is the high consumption of time and
      thus the running costs. The use of GeO2 as internal standard not only allows
      improved external calibration, but also semiquantitative determination of
      bromate, bromide, iodate and iodide without any calibration procedure.
      Furthermore, GeO2 can be used for all known types of anion exchange columns
      regardless of their construction principles. It is shown, that the analyte-to
      GeO2 ratio of four bromine and iodine species was nearly constant over 4 months
      and almost independent from the ICP-MS instrumental settings. The quantification
      by means of the analyte-to-GeO2 ratio for samples taken from a bromate round
      robin test shows that the values obtained are in excellent agreement with
      calibration curve and isotope dilution results.

PMID- 15503932
TI  - HIV update: emerging clinical evidence and a review of recommendations for the
      use of highly active antiretroviral therapy.
AB  - PURPOSE: This supplement will focus on recent trial data concerning the efficacy
      of certain nucleoside reverse transcriptase inhibitor (NRTI)-based highly active
      antiretroviral therapy (HAART) regimens, the most recent guidelines from the
      Department of Health and Human Services (DHHS) for the timing of antiretroviral
      (ARV) therapy initiation, and recommended ARV drug classes for managing treatment
      naive patients with HIV. SUMMARY: When choosing an initial regimen for the
      treatment of HIV, it is important to carefully consider therapeutic goals. These
      goals include choosing HAART that is likely to maximally suppress viral
      replication, maintain or restore immunologic function, improve quality of life,
      and reduce HIV-related morbidity and mortality. The evidence-based DHHS
      guidelines recommend HAART regimens that are non-nucleoside reverse transcriptase
      inhibitor (NNRTI)- or protease inhibitor (PI)-based. DHHS, however, does not
      recommend the use of triple-NRTI therapy for the initial treatment of HIV unless
      a preferred or alternative NNRTI- or PI-based regimen cannot be used. This
      recommendation concerning triple-NRTI therapy is supported by results from recent
      trials that demonstrated inferior outcomes with triple-NRTI-containing regimens
      compared with NNRTI- or PI-based HAART regimens. The timing for initiation of ARV
      therapy continues to change over time as the DHHS guidelines have evolved.
      Although the benefits of initiating ARV when CD4 cell count is < 200 cells/mm3
      are well established, the use of early versus late initiation of ARV therapy in
      patients with CD4 cell counts > 200 cells/mm3 has its own benefits and drawbacks.
      CONCLUSION: To successfully manage people with HIV, it is crucial to find a
      balance between ARV potency, tolerability, safety, and convenience while
      providing durable viral suppression.

PMID- 15503934
TI  - Top 10 dental office technology issues.

PMID- 15503933
TI  - Dental lasers: possibilities and benefits.

PMID- 15503935
TI  - Consumer-directed care--the time is now!

PMID- 15503936
TI  - Promoting dentistry as a career for minorities.

PMID- 15503937
TI  - A message of hope.

PMID- 15503938
TI  - Dr. Martin Deranian--profile of a collector.

PMID- 15503939
TI  - Massachusetts residents rank third nationally in health and social standings.
AB  - Residents of Massachusetts are positioned at almost the highest/most favorable
      end of all state rankings based on an overall listing of health, social
      conditions, and services. However, while these statistics are encouraging, they
      are not uniform throughout all population groups in the state. The challenge is
      to move beyond complacency with current standings to reach those in need.

PMID- 15503940
TI  - Ulcerative tongue lesion secondary to cytomegalovirus.

PMID- 15503941
TI  - A clinico-pathologic correlation. Dermoid cyst.

PMID- 15503942
TI  - It's in the cards.

PMID- 15503943
TI  - [Jose Ribera y Sans (1852-1912). Our first pediatric surgeon].

PMID- 15503944
TI  - [Use of ureterocalicostomy in child].
AB  - INTRODUCTION: There are many clinical situations in wich it may be difficult to
      perform appropriately an anastomosis between the renal pelvis and the proximal
      portion of the uretersafely. Preservation of the organ depens upon the
      availability of surgical resources. In fact, that principle becomes particularipy
      significant when dealing with children. OBJECTIVES: To describe different
      clinical and surgical situations in wich the successful performance of
      ureterocalicostomy has enable us to maintain three renal units with function from
      child patients and without complications. METHOD AND PATIENTS: Three children
      aged 8, 4 and 1 year were submitted to surgery because of pyelocaliceal lithiasis
      in the first case and secundary ureteropelvic stenosis in the remaning two cases.
      RESULTS: With a median follow-up of 12 months, all three renal units were
      preserved and, according to the isotopic study, functionality was improved in the
      two cases of ureteropelvic obstruction and the normal preoperative function was
      preserved in the first case. No complications occurred either during the
      immediate postoperative period or up to the date of this review. CONCLUSION:
      Ureterocalicostomy should be considered a suitable alternative in different
      clinical situations in wich the ureteropelvic continuity could be compromised, or
      in cases of indundibulopelvic stenosis.

PMID- 15503945
TI  - [Alternative treatment of gastroesophageal reflux: endoluminal gastric
      plication].
AB  - Gastroesophageal reflux is a common chronic disorder that is presented in infants
      under different clinical pictures. Adolescents with heartburn, dependent on acid
      supression therapy is a group of patients refered with increased frequency to
      pediatric surgeons. To date, the accepted methods of management are long term
      medication or surgery. Recently, different endoscopic techniques have been
      described to treat gastroesophageal reflux. Endoscopic antireflux suturing is one
      of this developed methods. In this paper, we present the preliminary results in
      the treatment of pediatric patients with an endoscopic suturing device. The
      procedure was accomplished in six patients and the results were analized 6 months
      after the placement of the sutures. We have obtained an improvement in clinical
      symptoms reduction, in terms of frequency as well as in intensity. Acid
      supression therapy was also reduced significantly. There were no complications
      during the endoscopic procedure, neither in the postoperative course. Patients,
      were agree with the technique and the clinical results obtained. Endoscopic
      suturing is a safe procedure that can be an alternative in the treatment of
      selected patients with gastroesophageal reflux, in the pediatric age group.

PMID- 15503946
TI  - [Good results with Passerini's technique in severely masculinised female
      pseudohermaphroditism].
AB  - In female pseudohermaphroditism due to congenital adrenal hyperplasia (CAH), some
      cases develope a very important masculinization degree with a high outlet of the
      vagina above the outern urethral sphincter. There are several surgical techniques
      to solve this problem. Our group uses Passerini's thecnique since 1990. 9 Girls
      with CAH with extreme masculitation (IV and V Prader degree) have been operated
      with this technique. The age at intervention varies between 9 months and 3 years,
      with a follow-up between 1 and 12 years. All these patients had hormonal studies,
      demostrating a deficiency of 21-hydroxilase in 8 cases and a deficiency of 11-B
      hydroxilase in one case. To determine the vaginal outlet a genitography was
      performed in all cases, vaginoscopy in 7 cases and MNR in 2 cases. Passerini's
      technique consists of two phases: the first step has the objective of forming the
      distal 2/3 of the vagina using the skin and the urethral mucosa of the phallus.
      At the second time transtrigonal way is performed to access the vagina which is
      desinserted from its urethral outlet and anastomosed with the distal neovagina.
      There were no significative complications in immediate time. The esthetic result
      is acceptable in all cases, although one case had to be surgically repaired
      because of a prominent vulvar flap. We use vaginoscopy to prove vaginal
      permeability in all cases although one of them developed adherences around the
      anastomosis. This severe genital malformation, very uncommon, has a difficult
      surgical solution. Passerini's technique allows, with less complications, to
      create an acceptable outer genitals at early age and only in one surgical time.

PMID- 15503947
TI  - [Surgical treatment of the GER with Boix-Ochoa technique. Long term results].
AB  - The Boix-Ochoa technique enable hipercorrection of the gastroesophageal reflux
      (GER), avoiding the disphagia and allowing the eructing capability as a
      consequence of the fundoplication procedure. MATERIAL AND METHODS: During the
      last decade 102 children were surgically treated using the Boix-Ochoa technique.
      The age range was 4.93 +/- 3.80 years. All patients have previously been studied
      with Xray, esophageal manometry, pHmetry during 24 h, and eventually with medical
      treatment. Failure of the medical treatment lead to the surgical treatment with
      the Boix-Ochoa technique. RESULTS: After surgery, 24 h controls of esophageal
      pHmetry showed reflux indexes greater than 5 in six patients. Two of them had
      neurological pathology and one of them suffered peptic stenosis previously
      treated by means of mechanical dilatation. The rest of patients showed normal
      value of reflux indexes after surgery. CONCLUSIONS: Excluding the esophageal
      atresia and caustic stenosis, the Boix-Ochoa technique is the best choice for the
      surgical treatment of GER.

PMID- 15503948
TI  - [Midgut malrotation risk in abdominal wall defect].
AB  - BACKGROUND: Midgut malrotation has a low incidence (0.5-1% at necropsies) and it
      is a rare symptomatic condition. Nevertheless it is often associated to clinical
      situations with a high morbility and mortality and it could complicate them. Our
      aim is to study the patients treated for abdominal wall defects and who have
      suffered complications due to non-treated malrotation at first surgery. METHODS:
      We retrospectively studied the charts of patients diagnosed of abdominal wall
      defects in our hospital from 1993 to 2002. We reviewed the initial treatment, the
      associated morbility and any new surgical treatment needed. RESULTS: During this
      10-year period, 110 abdominal wall defects were managed: 56 congenital
      diaphragmatic hernias, 30 onphaloceles and 14 gastroschisis; overall 79 of these
      100 patients survived and were included in this study. Eleven patients had
      symptoms due to bowel malrotation during the follow-up period. In 1 case the
      clinical picture had an acute onset as a volvulus that required extensive gut
      resection; another patient presented as a persistent gastrocutaneous fistula
      after removal of a gastrostomy tube; in the remaining 9, symptoms were always of
      classical intestinal obstruction. The malrotation was never treated during the
      initial surgical procedure for abdominal wall defect; later on, Ladd procedure
      was always the definitive treatment. CONCLUSIONS: Due to local conditions during
      first abdominal wall surgery that limit the evaluation of the malrotation, we
      must think about it when we find obstructive symptoms any time during life.

PMID- 15503949
TI  - [Pyeloplasty follow-up. How and how long?].
AB  - INTRODUCTION: Some controversies still persist about the pueloplasty follow-up
      and this study aims to determine which test should be done in these patients
      during the follow-up and for how long these patients should be under control.
      PATIENTS AND METHODS: Forty six children who underwent to pueloplasty were
      retrospectively reviewed and those with contralateral renal abnormalities were
      excluded from study. Six children were lost to follow-up and were excluded. Of 40
      p (25 M, 14 F) who fulfilled the requirements of this study, 28 were diagnosed
      prenatally and 28 had a left UPJ obstruction. All children were diagnosed by
      renal ultrasound, diuretic renography and excretory urogram (except 2). Mean age
      at Anderson Hynes pyeloplasty was 5.1 months and mean follow-up was 6.1 years.
      Renal ultrasound at 3 months and every year, and a diuretic renography at 1 year
      were performed in all children during follow-up. In some of them diuretic
      renography was repeated. RESULTS: At 3 months renal ultrasound demonstrated a
      significant hydronephrosis decrease in all children (p < 0.0001) but not in
      further controls. Differential renal function remained unchanged after
      pyeloplasty and during follow-up. However, there was a significant UPJ drainage
      improvement after pyeloplasty and during follow-up (p < 0.0001, p < 0.005). Any
      child needed a second pyeloplasty procedure and all of them showed a normal UPJ
      drainage in the antegrade ureterogram performed on the 5th postoperative day,
      except one. CONCLUSIONS: Differential renal function did not improve after
      pyeloplasty in our children. If renal ultrasound 3 months after pyeloplasty
      demonstrated a significant hydronephrosis decrease and at 1 year diuretic
      renography reveals a normal UPJ drainage any change should be expected in the
      long-term follow-up.

PMID- 15503950
TI  - [Congenital solid tumors. A thirteen-year review].
AB  - Tumors diagnosed during the first month of life are infrequent: 0.5 to 2% of all
      childhood neoplasms. This is an interesting group of tumors because their type,
      relative incidence, natural history and response to treatment differ from those
      seen in older children. AIM: To contribute the experience of our institution in
      congenital tumors the last 13 years. MATERIAL AND METHODS: The records of all
      neonates (< 31 days old) diagnosed with solid tumors since January 1990 to
      December 2002 have been retrospectively reviewed. RESULTS: Twenty-seven neonates
      have been diagnosed with tumors in the last 13 years. Thirteen patients (48%)
      were prenatally diagnosed. Nine babies were diagnosed at the initial neonatal
      exam (40% of those diagnosedd after birth). Neuroblastoma was the commonest tumor
      (10 cases, 37%), of which 4 were stage I, 4 stage IV-S and 2 stage III. There
      were 8 teratomas (3 sacrocoxigeal, 1 retroperitoneal, 1 in the CNS, 1 orbitary
      and two oronasal), two hepatic tumors (1 hepatoblastoma, 1 hemangioendothelioma,
      two CNS tumors, two giant nevus (one on a hamartoma), and one each Wilms tumor,
      infantile fibrosarcoma and myofibroblastic tumor. Treatment was surgical
      resection alone in 17 cases (68%) and surgery + chemotherapy in 8 (32%) (5
      neuroblastomas, one CNS tumor, one Wilms tumor and one presacral teratoma who
      developed a yolk sac tumor); 3 patients died (11%): one at surgery, one of
      tumoural airway obstruction at birth and one with craniopharyngioma. Among the 14
      tumors that were initially not malignant, two can be locally agressive, one was
      an immature teratoma, the giant nevus with hamartoma developed in situ melanoma,
      the other nevus had meningeal melanosis with hydrocephalus, and one mature
      presacral teratoma developed a yolk sac tumor. CONCLUSIONS: Diagnosis of
      congenital tumors is performed earlier in recent years due to the wide use of
      prenatal ultrasound. Their natural history is more benign than in other age
      groups, except for CNS tumors and very large or obstructing tumors. The
      histological patern is not determinant of the outcome. Complete surgical excision
      is the treatment of choice, most cases not need adjuvant chemotherapy. We ought
      to pass this message on to our colleagues in prenatal diagnosis, so parents get
      reliable information.

PMID- 15503951
TI  - [Management of infantile subglottic hemangioma].
AB  - INTRODUCTION: Subglottic hemangioma is an unusual lesion which can be treated in
      various ways. Multiple therapeutic attitudes with variable clinical results have
      been described. We present our experience in the management of these patients.
      PATIENTS AND METHODS: During last the three years we have treated four patients
      with subglottic hemangioma. The mean age was of 4.5 +/- 2.8 months and the mean
      weight of 6.9 +/- 2.04 kg. We present its presenting symptoms, location and size
      of the lesion, grade of obstruction (according to the classification of
      subglottic stenosis of Cotton), the treatment applied, complications and results
      in the long term. RESULTS: The lesions produced a mean obstruction of 83.75% of
      the airway (range 75-90%), being located in the right posterolateral region (2),
      left posterolateral region (1) and the last was completely to circulate. All the
      patients have been treated initially with steroids, but recurrence of symptoms
      when steroid dosage was decreased. All angiomas were removed surgically by
      submucous resection. No tracheotomy was performed. One patients developed a grade
      III subglottic stenosis that required an open surgery (laryngotracheoplasty with
      anterior a posterior graft). One patien suffered an overwhelming sepsis probably
      secondary to medical treatment. All patients had not had further respiratory
      difficulties. Postoperative follow-up is 18 months (range from 6 months to 3
      years). CONCLUSIONS: Treatment of subglottic hemangioma is difficult to
      standarize. Treatment with steroids have many adverse effects in children. The
      surgical treatment offer a good option in the treatment of the angiomas of great
      size. Traqueostomy as must be avoided in the management of these patients.

PMID- 15503952
TI  - [Ultrasonography for surgical pathology discrimination in acute abdominal pain.
      Prospective study].
AB  - Abdominal ultrasonographic study is a part of the acute abdominal pain diagnosis
      protocol in our hospital. As an internal quality assessment, we performed a six
      month prospective study, including those patients who meet one of these
      requirements: 1st the reason for attendance being non-traumatic abdominal pain
      2nd an abdominal ultrasonography achieved at the hospital. Collected data
      included: demographic characteristics, presenting sign and symptoms, test
      results, ultrasonography, final diagnosis and treatment. Children attended to the
      hospital were evaluated through clinical findings to verify concordance between
      clinical and ultrasound diagnosis, and patients who did not stay at the hospital
      had telephone follow-up in 2 weeks. A total of 136 patients underwent
      ultrasonography (7 children did not cooperate and were discarded): 74 females and
      55 males with a mean age of 9.52 years. Admission was required in 63 subjects and
      66 were sent home after clinical evaluation. Abdominal ultrasonography was
      performed by the radiologist on duty (occasionally paediatric radiologist).
      Ultrasound examination, for acute appendicitis, had a sensitivity of 94.8%,
      specificity of 98.8%, positive predictive value of 97.3% and negative predictive
      value of 97.8%. Abdominal ultrasonography has showed usefulness for surgical
      pathology discrimination in acute abdominal pain. When ultrasonography is
      inconclusive, clinical follow-up and periodical ultrasonography results in a
      positive change in management and treatment.

PMID- 15503953
TI  - [Results of an intestinal transplantation program in Spain. Five years later].
AB  - BACKGROUND: More than two thirds of all intestinal transplantations (ITx)
      performed around the world correspondent to recipients younger than 18.
      OBJECTIVE: To analyze our 5-year experience in pediatric ITx. PATIENTS: We
      assessed the outcome of the 19 children included in list out of 41 patients
      considered for ITx from 1997. The main cause of intestinal failure was short
      bowel syndrome (14) followed by intestinal motility disorders (3) and congenit
      disorders of intestinal epithelium (CDIE) (2). The median of age, at the moment
      of including in the list, was 0.9 years (range 0.4-17) and median of weight was
      6.4kg (range 0.4-29.3). Ten children were included for liver and small bowel
      transplantation (LSBTx), 7 to isolated small bowel (SBTx), and 2 for
      multivisceral transplantation (MVTx). Indications for SBx were hepatic
      fibrosis/cirrhosis (10), hepatic fibrosis in evolution (5) (to avoid later
      LSBTx), intractable diarrhoea (1), recurrent line infections (1), lost of central
      vein access (1), and bad quality of life in one. RESULTS: Five children died in
      the waiting list, after a median time of 325 days (range 19-581). Seven remain in
      the waiting list (median 139 days, range 30-778). In 3 of these the indication
      changed from SBTx to LSBTx because of progression to end stage liver disease. Six
      children recieved seven grafts (1 MVTx, 4 LSBTx, 2 SBx) after a median time in
      the waiting list of 352 days (range 66-732). Six out of seven grafts achieved
      normal function and all survivals reached full digestive autonomy after Tx. We
      had to rejection episodes, one with good response to medical treatment and one
      that required removal of intestinal allograft and later LSBTx. Two children died
      1 because of problem not related to the procedure (hemorrage following liver
      biopsy) and one girl died 29 months after transplant due to post-transplantation
      lymphoproliferative disease. CONCLUSIONS: ITx is a realistic alternative in our
      country for children with intestinal failure. The main problems are immunologic
      (rejection, lynphoproliferative and disease) Shortage of small weight donors is a
      dramatic limitation that prompts the discussion of surgical alternatives.

PMID- 15503954
TI  - [Thoracoscopic repair of esophageal atresia].
AB  - We present the first three cases of esophageal atresia with tracheoesophageal
      fistula treated with a thoracoscopic approach in our Service. The technique was
      accomplished through three trocar inserted in the right hemithorax. Carbon
      dioxide insufflation was required for lung retraction Primary correction was
      carried out in all the cases without major perioperative complications. The mean
      surgical time was 240 minutes. One patient had an anastomotic leak, resulting in
      a complicated postoperative course. The leak healed on conservative treatment.
      The others two patients were fed at the seventh postoperative day. Mean hospital
      stay in these cases was 12 days. Although thoracoscopic repair of esophageal
      atresia with fistula is a currently feasible technique that offers different
      advantages on the conventional open technique, a greater number of cases is
      needed in order to advance in the learning curve and determine the exact place
      that this technique can have in the future treatment of esophageal atresia.

PMID- 15503955
TI  - [Usefulness of video-assisted thoracic surgery techniques in intra-thoracic mass
      resection in children].
AB  - The progressive advances in Minimally Invasive Surgical Procedures, are applied
      presently to the surgical treatment of intra-thoracic injuries in children by way
      of Video-Assisted Thoracic Surgery (VATS) techniques. We present the complete
      findings of two intra-thoracic masses, in an infant and in a school-aged child,
      with the use of the VATS technique. The operative technique is detailed in each
      case. We conclude that the lack of invasiveness and cost-efficiency of VATS the
      technique, constitute it as being the first choice in the treatment of intra
      thoracic masses in children.

PMID- 15503956
TI  - Monitoring water content of rat lung tissue in vivo using microwave
      reflectometry.
AB  - Measurement of lung water is an important diagnostic means of assessing pulmonary
      oedema. Water content affects the dielectric spectrum at microwave frequencies,
      but quantification is still a problem. A new lung tissue model is presented that
      allows the calculation of water content from dielectric permittivity. The
      dielectric permittivity of lung tissue was measured by microwave reflectometry
      using a non-invasive surface probe. During perfusion of rat lungs (n = 22) with
      blood, injury was induced by interruption of the blood supply for a duration
      between 0 (control) and 2 h. Water content was assessed from dielectric
      permittivity using a new mixture formula and was also determined by drying and
      weighing. The mixture formula allows for the dielectric polarisation of water,
      dry matter and air in the tissue. A linear correlation was found between total
      water content determined from dielectric permittivity and that from drying and
      weighing (y= 1.001x, R2 = 0.8). Lung injury showed an increase in total water
      content from 80.9 +/- 1.2% (control) to 84.1 +/- 0.9% (p < 0.01). The analysis of
      dielectric permittivity data at microwave frequencies with the new tissue model
      is sensitive enough to detect water accumulation produced by lung injury and it
      can be used to monitor total water content without tissue destruction.

PMID- 15503957
TI  - Experimental investigation of the mammary gland tumour phantom for multifrequency
      microwave radio-thermometers.
AB  - Microwave radiometry is a spectral measurement technique for resolving the
      electromagnetic radiation of matter when its temperature is above absolute zero.
      The radio-thermometer utilises this technique and consequently can provide
      temperature distributions in subcutaneous biological tissues. A new phantom was
      proposed that imitates a mammary gland tumour, and the brightness temperature was
      observed using radio-thermometers operated at different frequencies, 1.75GHz and
      3GHz. The proposed phantom, simulating heat diffusion propagated by tissues
      around real tumours, revealed that the thermal characteristics of the tumour
      imitator were well matched to the heat transfer properties of a real tumour and a
      proportional linear relationship between the location of the tumour imitator and
      the brightness temperature in a homogenous medium was established. From
      experiments using the proposed mammary gland tumour phantom and a clinical trial
      on patients with breast cancer, it could be concluded that a radio-thermometer
      with a short wavelength (lambda = 10cm, i.e. f= 3GHz) is useful to resolve a
      thermal anomaly at a shallow depth in an homogenous medium such as a breast.

PMID- 15503958
TI  - Experimental evaluation of computerised tomography point spread function
      variability within the field of view: parametric models.
AB  - The objective of the paper was to validate non-linear parametric models of
      computerised tomography point spread function (PSF), to investigate the role of
      model parameters and to verify the effect of different imaging conditions on
      estimated parameters. These models were then to be used experimentally to
      estimate the variation of PSF shape within the field of view of a scanner. Two
      parametric models of the PSF are presented. The Gaussian model is appropriate
      when PSF values are positive, and the damped cosine model can account for
      negative values. These models are non-linear and fully two-dimensional and do not
      assume radial symmetry. The models were fitted to images of a point source. The
      models accounted for over 99% of the variance in the PSF signal. Errors in
      modulation transfer function were limited to 5% when the appropriate model was
      selected. The difference in the blurring characteristics of three image
      reconstruction filters was well quantified by shape parameters, and position
      parameters located the PSF with subpixel accuracy. With a point source located
      50mm directly above the centre of the field of view, the PSF was found to be
      anisotropic.

PMID- 15503959
TI  - Objective facial paralysis grading based on Pface and eigenflow.
AB  - To provide physicians with an objective and quantitative measurement of single
      sided facial paralysis, the paper presents a computer-based approach that is
      different from the nine existing, subjective and hand-performed international
      scales, such as House-Brackman. For voluntary expressions of a patient, this
      approach used Pface, which stems from Dface, to measure the asymmetry between two
      sides of the face and used eigenflow to measure the expression variations between
      the patient and normal subjects. The results from Pface and eigenflow were then
      combined by the support vector machine produce to Pdegree. A study of 25 subjects
      revealed that Pdegree could differentiate paralysis states (Pdegree > or = 0) and
      normal states (Pdegree < 0), with the ability to grade facial paralysis
      automatically. Moreover, the Pface of specific facial areas can be used in the
      supervision of the rehabilitation process.

PMID- 15503960
TI  - Pattern recognition approach to the detection of single-trial event-related
      functional magnetic resonance images.
AB  - Functional magnetic resonance imaging (FMRI) is an imaging technique for
      determining which regions of the brain are activated in response to a stimulus or
      event. Early FMRI experiment paradigms were based upon those used in positron
      emission tomography (PET), i.e. employing a block design consisting of extended
      periods of 'on' against 'off' activations. More recent experiments were based on
      event-related FMRI, harnessing the fact that very short stimuli trains or single
      events can generate robust responses. FMRI data suffer from low signal-to-noise
      ratios, and typical event-related experiment paradigms employ selective averaging
      over many trials before using statistical methods for determining active brain
      regions. The paper reports a pattern recognition approach to the detection of
      single-trial FMRI responses without recourse to averaging and at modest field
      strengths (1.5T). Linear discriminant analysis (LDA) was applied in conjunction
      with different feature extraction techniques. Use of the unprocessed data samples
      as features resulted in single-trial events being classified with an accuracy of
      61.0 +/- 9.5% over five subjects. To improve classification accuracy, knowledge
      of the ideal template haemodynamic response was used in the feature extraction
      stage. A novel application of parametric modelling yielded an accuracy of 69.8 +/
      6.3%, and a matched filtering approach yielded an accuracy of 71.9 +/- 5.4%.
      Single-trial detection of event-related FMRI may yield new ways of examining the
      brain by facilitating new adaptive experiment designs and enabling tight
      integration with other single-trial electrophysiological methods.

PMID- 15503961
TI  - Quantification of left ventricular modification in weightlessness conditions from
      the spatio-temporal analysis of 2D echocardiographic images.
AB  - Two-dimensional echocardiography (2DE) performed during flights with a parabolic
      trajectory to simulate weightlessness provides a unique means to study left
      ventricular (LV) modifications to prevent post-flight orthostatic intolerance in
      astronauts. However, conventional analysis of 2DE is based on manual tracings and
      depends on experience. Accordingly, the aim was objectively to quantify, from 2DE
      images, the LV modifications related to different gravity levels, by applying a
      semi-automated level-set border detection technique. The algorithm validation was
      performed by the comparison of manual tracing results, obtained by two
      independent observers with 20 images, with the semi-automated measurements. To
      quantify LV modifications, three consecutive cardiac cycles were analysed for
      each gravity phase (1 Gz, 1.8 Gz, 0 Gz). The level-set procedure was applied
      frame-by-frame to detect the LV endocardial contours and obtain LV area against
      time curves, from which end-diastolic (EDA) and end-systolic (ESA) areas were
      computed and averaged to compensate for respiratory variations. Linear regression
      (y = 0.91x + 1.47, r = 0.99, SEE:0.80cm2) and Bland-Altman analysis (bias = -0.58
      cm2, 95% limits of agreement= +/- 2.14cm2) showed excellent correlation between
      the semi-automatic and manually traced values. Inter-observer variability was
      5.4%, and the inter-technique variability was 4.1%. Modifications in LV
      dimensions during the parabola were found: compared with 1 Gz values, EDA and ESA
      were significantly reduced at 1.8 Gz by 8.8 +/- 5.5% and 12.1 +/- 10.1%,
      respectively, whereas, during 0 Gz, EDA and ESA increased by 13.3 +/- 7.3% and
      11.6 +/- 5.1%, respectively, owing to abrupt changes in venous return. The
      proposed method resulted in fast and reliable estimations of LV dimensions, whose
      changes caused by different gravity conditions were objectively quantified.

PMID- 15503962
TI  - Respiratory acoustic thoracic imaging (RATHI): assessing deterministic
      interpolation techniques.
AB  - As respiratory sounds contain mechanical and clinical pulmonary information,
      technical efforts have been devoted during the past decades to analysing,
      processing and visualising them. The aim of this work was to evaluate
      deterministic interpolating functions to generate surface respiratory acoustic
      thoracic images (RATHIs), based on multiple acoustic sensors. Lung sounds were
      acquired from healthy subjects through a 5 x 5 microphone array on the anterior
      and posterior thoracic surfaces. The performance of five interpolating functions,
      including the linear, cubic spline, Hermite, Lagrange and nearest neighbour
      method, were evaluated to produce images of lung sound intensity during both
      breathing phases, at low (approximately 0.5ls(-1)) and high (approximately 1.0ls(
      1)) airflows. Performance indexes included the normalised residual variance nrv
      (i.e. inaccuracy), the prediction covariance cv (i.e. precision), the residual
      covariance rcv (i.e. bias) and the maximum squared residual error semax (i.e.
      tolerance). Among the tested interpolating functions and in all experimental
      conditions, the Hermite function (nrv=0.146 +/- 0.059, cv= 0.925 +/- 0.030, rcv =
      -0.073 +/- 0.068, semax = 0.005 +/- 0.004) globally provided the indexes closest
      to the optimum, whereas the nearest neighbour (nrv=0.339 +/- 0.023, cv = 0.870 +/
      0.033, rcv= 0.298 +/- 0.032, semax = 0.007 +/- 0.005) and the Lagrange methods
      (nrv = 0.287 +/- 0.148, cv = 0.880 +/- 0.039, rcv = -0.524 +/- 0.135, semax =
      0.007 +/- 0.0001) presented the poorest statistical measurements. It is concluded
      that, although deterministic interpolation functions indicate different
      performances among tested techniques, the Hermite interpolation function presents
      a more confident deterministic interpolation for depicting surface-type RATHI.

PMID- 15503963
TI  - Using independent component analysis to remove artifact from
      electroencephalographic measured during stuttered speech.
AB  - The electro-encephalographic (EEG) activity of people who stutter could provide
      invaluable information about the association of neural processing and stuttering.
      However, the EEG has never been adequately studied during speech in which
      stuttering naturally occurs. This is owing, in part, to the masking of the EEG
      signal by artifact from sources such as the speech musculature and from ocular
      activity. The aim of this paper was to demonstrate the ability of independent
      component analysis (ICA) to remove artifact from the EEG of stuttering children
      recorded while they are speaking and stuttering. The EEG of 16 male children who
      stuttered and 16 who did not stutter was recorded during a reading task. The
      recorded EEG that contained artifact was then subjected to ICA. The results
      demonstrated that the EEG assessed during stuttered speech had substantially more
      noise than the EEG of speech that did not contain stuttering (p < 0.01).
      Furthermore, it was shown that ICA could effectively remove this artifact in all
      16 children (p < 0.01). The results from one child highlight the findings that
      ICA can be used to remove dominant artifact that has prevented the study of EEG
      activity during stuttered speech in children.

PMID- 15503964
TI  - Multiple-electrode nerve cuffs for low-velocity and velocity-selective neural
      recording.
AB  - In the paper, a method using multiple-electrode nerve cuffs is presented that
      enables electroneurographic signals (ENG) to be recorded selectively by action
      potential velocity. The theory uses a one-dimensional model of the electrodes in
      the cuff. Using this model, the transfer function for a single tripole is
      derived, and it is shown that more than one tripole signal can be recorded from
      within a cuff. When many tripole signals are available and are temporally aligned
      by artificial delays and summed, there is a significant increase in the amplitude
      of the recorded action potential, depending on the cuff length and the action
      potential velocity, with the greatest gain occurring for low velocities. For
      example, a cuff was considered that was constrained by surgical considerations to
      30 mm between the end electrodes. For action potentials with a velocity of 120 m
      s(-1), it was shown that, as the number of tripoles increased from one, the peak
      energy spectral density of the recorded output increased by a factor of about 1.6
      with three tripoles, whereas, for 20 m s(-1), the increase was about 19, with ten
      tripoles. The time delays and summation act as a velocity-selective filter. With
      consideration of the energy spectral densities at frequencies where these are
      maximum (to give the best signal-to-noise ratio), the tuning curves are presented
      for these velocity-selective filters and show that useful velocity resolution is
      possible using this method. For a 30 mm cuff with nine tripoles, it is
      demonstrated that it is possible to resolve at least five distinct velocity bands
      in the range 20-120m s(-1).

PMID- 15503965
TI  - Infusion technique can be used to distinguish between dysfunction of a
      hydrocephalus shunt system and a progressive dementia.
AB  - In a deteriorating shunted patient with hydrocephalus, an investigation of shunt
      function is often performed to distinguish a dysfunctioning shunt from an
      aggravated condition of the disease. The paper illustrates how a lumbar
      cerebrospinal fluid (CSF) infusion method can be used to evaluate post-operative
      deterioration in a shunted patient in order to give the physician valuable
      support in the shunt revision decision. A 77-year-old man with hydrocephalus was
      treated operatively by the insertion of a CSF shunt. Owing to shunt failure, the
      shunt was revised twice during a 5 year period. Using a computerised infusion
      technique method, with two needles placed in the lumbar subarachnoid space, the
      CSF dynamic system was determined pre- and post-operatively with the functioning
      as well as the dysfunctioning shunts. The data were verified with a bench-test of
      the extirpated CSF shunt. There was a significant difference in conductance G
      between CSF systems with an open shunt and CSF systems with no shunt or an
      occluded shunt (deltaG= 38 mm3 s(-1) kPa(-1), p = 0.014, n= 7, ANOVA). CSF
      dynamics investigations, with and without a shunt, can give valuable clinical
      support in the management of a deteriorating hydrocephalus patient. With further
      development of the lumbar infusion method moving towards easy-to-use equipment,
      there is potential for widespread clinical use.

PMID- 15503966
TI  - Three-dimensional numerical simulations of physiological flows in a stented
      coronary bifurcation.
AB  - When atherosclerotic lesions are found within a coronary bifurcation, a double
      stent implantation is sometimes required to treat the disease of each branch. The
      clinical procedure can result in the positioning of several stents in the
      bifurcation. In the study, physiological flows in typical configurations of such
      stented coronary bifurcations were numerically modelled using the finite volumes
      method. Two deployed Palmaz stents were inserted in a 90 degrees coronary
      bifurcation, simulating a double stent implantation. As the geometric position of
      the metallic stent cells can vary, several models of broken cells were proposed
      and compared to characterise the influence of the stent struts protruding into
      the collateral branch. Flow features in the bifurcation surroundings changed from
      one model to another. These changes could lead to the occurrence of flow stasis
      and also of recirculation areas downstream from the struts, depending on the way
      the strut was opened. The stent struts protruding into the lumen of the
      collateral branch induced high values of shear stress at the stent wall of about
      20 N m(-2), which could stimulate platelet activation. In addition, these areas
      of high shear stress values were concomitant with areas of low shear stress
      values of about 0.5 Nm(-2). These regions could be prone to platelet adhesion and
      so to thrombo-embolic complications. The analysis of the flow field indicated
      that it would be judicious to use dedicated bifurcated stents to treat
      bifurcation lesions.

PMID- 15503967
TI  - Construction of realistic branched, three-dimensional arteries suitable for
      computational modelling of flow.
AB  - Routinely performed biplane digital coronary angiograms were used to construct a
      three-dimensional model of the coronary arteries. The technique took the images
      and automatically picked the centreline and radii in each. By reading the
      information contained in the DICOM format, the rotation angle between the two
      images could be ascertained, and the centreline in three dimensions could be
      determined. Once the centreline and radii had been calculated, a finite volume
      mesh of the artery was constructed that could be used as input into a fluid
      dynamics package that solves Navier-Stokes equations. A four-section method was
      adopted for constructing the mesh, utilising three tubular segments and a small
      junction section. The tubes were constructed automatically, and the junction
      procedure was semi-automated, maximising user-control over this region. A
      structured mesh was used for the tubes, and an unstructured mesh was used to
      model accurately the irregular shape of the junction. The accuracy of the
      reconstruction method was established by projection of a mesh onto an independent
      image of the same artery and the use of a coronary phantom. These tests, along
      with calibration of the edge detection, established an error of less than 2% in
      the model.

PMID- 15503968
TI  - Influence of illumination-collection geometry on fluorescence spectroscopy in
      multilayer tissue.
AB  - Device-tissue interface geometry influences both the intensity of detected
      fluorescence and the extent of tissue sampled. Previous modelling studies have
      often investigated fluorescent light propagation using generalised tissue and
      illumination-collection geometries. However, the implementation of approaches
      that incorporate a greater degree of realism may provide more accurate estimates
      of light propagation. In this study, Monte Carlo modelling was performed to
      predict how illumination-collection parameters affect signal detection in
      multilayer tissue. Using the geometry and optical properties of normal and
      atherosclerotic aortas, results for realistic probe designs and a semi-infinite
      source-detection scheme were generated and compared. As illumination-collection
      parameters, including single-fibre probe diameter and fibre separation distance
      in multifibre probes, were varied, the signal origin deviated significantly from
      that predicted using the semi-infinite geometry, The semi-infinite case under
      predicted the fraction of fluorescence originating from the superficial layer by
      up to 23% for a 0.2mm diameter single-fibre probe and over-predicted by 10% for a
      multifibre probe. These results demonstrate the importance of specifying
      realistic illumination-collection parameters in theoretical studies and indicate
      that targeting of specific tissue regions may be achievable through customisation
      of the illumination-collection interface. The device- and tissue-specific
      approach presented has the potential to facilitate the optimisation of minimally
      invasive optical systems for a wide variety of applications.

PMID- 15503969
TI  - Optimised robot-based system for the exploration of elastic joint properties.
AB  - Numerous publications provide measured biomechanical data relating to synovial
      joints. However, in general, they do not reflect the non-linear elastic joint
      properties in detail or do not consider all degrees of freedom (DOF), or the
      quantity of data is sparse. To perform more comprehensive, extended measurements
      of elastic joint properties, an optimised robot-based approach was developed. The
      basis was an industrial, high-precision robot that was capable of applying loads
      to the joint and measuring the joint displacement in 6 DOF. The system was
      equipped with novel, custom-made control hardware. In contrast to the commonly
      used sampling rates that are below 100 Hz, a rate of 4 kHz was realised for each
      DOF. This made it possible to implement advanced, highly dynamic, quasi
      continuous closed-loop controllers. Thus oscillations of the robot were avoided,
      and measurements were speeded up. The stiffness of the entire system was greater
      than 44 kNm(-1) and 22 Nm deg(-1), and the maximum difference between two
      successive measurements was less than 0.5 deg. A sophisticated CT-based
      referencing routine facilitated the matching of kinematic data with the
      individual anatomy of the tested joint. The detailed detection of the elastic
      varus-valgus properties of a human knee joint is described, and the need for high
      spatial resolution is demonstrated.

PMID- 15503970
TI  - Classification of basic daily movements using a triaxial accelerometer.
AB  - A generic framework for the automated classification of human movements using an
      accelerometry monitoring system is introduced. The framework was structured
      around a binary decision tree in which movements were divided into classes and
      subclasses at different hierarchical levels. General distinctions between
      movements were applied in the top levels, and successively more detailed
      subclassifications were made in the lower levels of the tree. The structure was
      modular and flexible: parts of the tree could be reordered, pruned or extended,
      without the remainder of the tree being affected. This framework was used to
      develop a classifier to identify basic movements from the signals obtained from a
      single, waist-mounted triaxial accelerometer. The movements were first divided
      into activity and rest. The activities were classified as falls, walking,
      transition between postural orientations, or other movement. The postural
      orientations during rest were classified as sitting, standing or lying. In
      controlled laboratory studies in which 26 normal, healthy subjects carried out a
      set of basic movements, the sensitivity of every classification exceeded 87%, and
      the specificity exceeded 94%; the overall accuracy of the system, measured as the
      number of correct classifications across all levels of the hierarchy, was a
      sensitivity of 97.7% and a specificity of 98.7% over a data set of 1309
      movements.

PMID- 15503971
TI  - Rate-responsive pacing using the atrio-ventricular conduction time: design and
      test of a new algorithm.
AB  - The cardio-circulatory system of chronotropic incompetent patients is unable to
      adapt heart rate adequately to the level of strain. A common therapy is the
      implantation of a pacemaker that stimulates the heart at a rate derived from a
      strain related sensor signal. The paper describes a new pacemaker concept that
      uses a well-defined time interval in the electrogram as a sensor parameter, the
      atrioventricular conduction time (AVCT). Identification experiments with patients
      delivered the stationary and dynamic behaviour of AVCT subject to variations in
      the exercise rate and the pacing frequency. Furthermore, it was demonstrated that
      AVCT is perturbed by respiratory activity. The new rate-responsive algorithm,
      which uses the internal model control principle, explicitly takes into account
      the closed-loop nature of the underlying system. The major design objectives
      were: extended range of the individual heart rate; effective attenuation of the
      respiratory-related disturbance; and stability. Seven patients undergoing
      incremental exercise were paced with this AVCT-based algorithm. The experiments
      confirmed the suitability of this concept with respect to the design goals. The
      patients' peak intrinsic heart rate at exercise was 100 +/- 20min(-1). When paced
      with the AVCT algorithm, the paced heart rate was 126 +/- 12min(-1). The increase
      was significant (26 +/- 13min(-1); 15 to 53 min(-1)), which clearly demonstrated
      the potential of this concept to restore chronotropic competence.

PMID- 15503972
TI  - Reduction of false arterial blood pressure alarms using signal quality assessment
      and relationships between the electrocardiogram and arterial blood pressure.
AB  - The paper presents an algorithm for reducing false alarms related to changes in
      arterial blood pressure (ABP) in intensive care unit (ICU) monitoring. The
      algorithm assesses the ABP signal quality, analyses the relationship between the
      electrocardiogram and ABP using a fuzzy logic approach and post-processes
      (accepts or rejects) ABP alarms produced by a commercial monitor. The algorithm
      was developed and evaluated using unrelated sets of data from the MIMIC database.
      By rejecting 98.2% (159 of 162) of the false ABP alarms produced by the monitor
      using the test set of data, the algorithm was able to reduce the false ABP alarm
      rate from 26.8% to 0.5% of ABP alarms, while accepting 99.8% (441 of 442) of true
      ABP alarms. The results show that the algorithm is effective and practical, and
      its use in future patient monitoring systems is feasible.

PMID- 15503973
TI  - Stroke volume and systolic time intervals: beat-to-beat comparison between
      echocardiography and ambulatory impedance cardiography in supine and tilted
      positions.
AB  - The aim of the study was to compare stroke volume (SV), ejection time (ET) and
      pre-ejection period (PEP) measurements obtained using a central haemodynamics
      ambulatory monitoring device based on impedance cardiography (ICG), in supine and
      tilted positions (60 degrees), with pulsed Doppler echocardiography as a non
      invasive reference method. The Holter-type ICG device was used for off-line, beat
      to-beat, automatic determination of SV, ET and PEP. ICG data were compared with
      those obtained simultaneously using pulsed Doppler echocardiography in the
      ascending aorta from a suprasternal projection, 1 min before and 10 min after
      tilting. The tests were performed in 13 young, healthy subjects (six men and
      seven women, aged 23-33 years). Linear regression between the measured values
      obtained for all subjects was described by the following formulas: SVicg= 13.9 +
      0.813 x SVecho (r = 0.857, SEE = 9.03, n = 496), ETicg = 16.8 + 0.987 x ETecho (r
      = 0.841, SEE=21.3, n = 496), PEPicg= 22.8 + 0.890 x PEPecho (r = 0.727, SEE =
      14.6, n = 496). The data showed that ambulatory impedance cardiography gives
      useful absolute values of SV and systolic time intervals measured in supine and
      tilted positions.

PMID- 15503974
TI  - Beat-to-beat noise removal in non-invasive His-bundle electrocardiogram.
AB  - His-bundle electrocardiogram micropotentials are usually obtained by serial
      signal averaging, because no acceptable, satisfactory solution for beat-by-beat
      removal of power-line interference and electromyographic noise has been found. A
      method has been developed for surface beat-to-beat His-bundle potential recovery,
      with the hypothesis that no distortion in the signal shape is admissible. It is
      based on consecutive power-line interference subtraction and wavelet-domain
      electromyographic noise suppression, modified to match the strict criteria for
      detecting low-amplitude His potentials. The beat-to-beat wavelet-domain Wiener
      filtering uses a pilot signal estimate obtained from a limited number (around 20)
      of heart beat averages. The method resulted in an improvement of more than 4.5 dB
      in the signal-to-noise ratio and more than 20% reduction in mean absolute error,
      both measured along the P-Q segment. It is applicable for ECG signals
      contaminated by moderate electromyogram noise, with an initial signal-to-noise
      ratio of 15 dB or higher.

PMID- 15503975
TI  - Evaluation of microfluidic blood gas sensors that combine microdialysis and
      optical monitoring.
AB  - It is shown that microdialysis-based blood gas (pH, pCO2 and pO2) optical sensors
      are stable for durations of several hours in blood. This performance is uncommon
      with many types of membrane sensor. Microdialysis techniques can be designed to
      ensure that the sweep microflow samples are in biochemical equilibrium with the
      bulk media, even after hours of exposure to the complex composition of blood. The
      rate of diffusion through the membrane is not the determining factor in sensor
      reading, as it is with other sensor techniques that consume the analyte. The
      sweep fluid 95% equilibration times for microdialysis fibres were approximately
      double in blood compared with buffer, reflecting slower diffusion of ions. This
      is in contrast to the equilibration of gases through silicone hollow-fibre
      membranes in blood, which showed unchanged equilibration times between blood and
      buffer. Sensor measurements correlate well with a blood gas analyser for up to 9
      h in blood, with correlation coefficients of 0.973 for the pO2 sensor 0.974 for
      the pCO2 sensor and 0.947 for the pH sensor. In blood, the sensors have
      precisions of 1.7 mmHg, 3.7 mmHg and 0.019 pH units and bias levels of -0.7 mmHg,
      1.2 mmHg and 0.002 pH units, for pO2, pCO2 and pH, respectively.

PMID- 15503976
TI  - Automatic estimation of endothelium cell density in donor corneas by means of
      fourier analysis.
AB  - One of the main clinical parameters expressing the health of a cornea is the cell
      density of its endothelium. This information is particularly important in an eye
      bank environment, where donor corneas are screened to assess their suitability as
      a human graft. Endothelium cell density is conventionally estimated by a long,
      tedious and error-prone manual counting procedure, performed by cornea experts on
      specimen images observed through an optical microscope. An alternative solution
      is proposed: a computer program that provides automatic estimation of cell
      density in donor corneas by analysing the spatial frequencies contained in the
      image. A circular band in the 2D discrete Fourier transform of the image is shown
      to contain the relevant information about the cell density. A system for
      extracting from this spatial frequency information an estimate of the cell
      density has been developed. A clinical evaluation of the proposed technique was
      performed on 18 corneas, where the densities provided by the proposed technique
      were compared with those manually obtained by two experts. The results showed an
      average percentage difference of 3% (maximum 19%), a value well within the
      measured inter-expert range of variability. The proposed automatic procedure
      confirmed its ability to estimate correctly corneal endothelium cell density.

PMID- 15503977
TI  - Evaluating psychosocial functioning in dental patients.
AB  - In order to make a reliable diagnosis and offer appropriate treatment, it is
      important that the dentist is aware of the role played by psychosocial factors in
      the origin and persistence of dental problems and has the ability to recognise
      their importance in the patient's overall presentation. This paper is an attempt
      to improve dentist's awareness of psychosocial issues and recognition of possible
      psychological problems in general dental practice. It focuses on directions for
      the gathering of information on patients through careful assessment prior to
      dental examination, covering patients biological or physical history and present
      symptoms, their social background, their psychological history and mental
      functioning, and the observation of their behaviour and mood. It is argued that
      interpreting these types of information will enable the dentist to be better
      prepared for any pitfalls that may arise in the course of treatment.

PMID- 15503978
TI  - Oral health in Israel--a review of surveys over several decades.
AB  - This review covers oral health surveys carried out in various communities in
      Israel over four decades. The general trends were for increasing caries
      prevalence from early surveys in the 1950s and 1960s up to the 1980s as evidenced
      by the rising DMFT. Treatment levels had increased since the 1980s, and there is
      a national decrease in caries experience. But there were still some communities
      and social groups with levels of untreated caries and other treatment needs.
      There is a continued need for strengthened oral health promotion and other
      preventive oral health measures at a community and public health level.

PMID- 15503979
TI  - Amalgam tattoo (amalgam pigmentation) of the oral mucosa: clinical
      manifestations, diagnosis and treatment.
AB  - Amalgam tattoo is an iatrogenic lesion caused by traumatic implantation of dental
      amalgam into soft tissue. Amalgam tattoo is the most common localized pigmented
      lesion in the mouth. In a study of a mass screening oral examination in the
      United States, it was found in about 0.4-0.9% of the adult population and in
      Sweden in about 8%. Clinically, amalgam tattoo presents as a dark gray or blue,
      flat macule located adjacent to a restored tooth. Most are located on the gingiva
      and alveolar mucosa followed by the buccal mucosa and the floor of the mouth.
      Microscopic examination reveals that amalgam is present in the tissues in two
      forms: as irregular dark, solid fragments of metal or as numerous, discrete fine,
      brown or black granules dispersed along collagen bundles and around small blood
      vessels and nerves. In most lesions, it is presented in both forms. The biologic
      response to the amalgam is related to particle size, quantity and elemental
      composition of the amalgam. Large fragments often become surrounded by dense
      fibrous connective tissue. Smaller particles are associated with mild to moderate
      chronic inflammatory response with individual macrophages engulfing small amalgam
      particles. Occasionally, the reaction takes the form of foreign body granuloma in
      which macrophages and multinucleated giant cells are present. Some of the
      multinucleated giant cells also contain amalgam particles. Diagnosis of amalgam
      tattoo is usually obvious from the location and clinical appearance. A radiograph
      is recommended to confirm the presence of metallic particles, but absence of
      radiographic evidence does not rule out the possibility, since particles are
      often too fine or widely dispersed to be visible on radiographs. When there is no
      radiographic evidence or an adjacent restored tooth, biopsy is recommended to
      rule out an early melanoma. Once the diagnosis of amalgam tattoo has been
      established, no additional treatment is necessary except for cosmetic reasons. If
      the pigmentation is cosmetically unacceptable, surgical excision and
      transplantation of oral mucosal tissue has been suggested. Q-switched ruby laser
      and Q-switched alexandrite laser have also been used with favorable results.

PMID- 15503980
TI  - [Healing of osseous defects by guided bone regeneration using ribose cross linked
      collagen membranes].
AB  - The ultimate goal of periodontal therapy has long been the complete regeneration
      of the periodontal attachment apparatus. Guided Tissue Regeneration (GTR) and
      Guided Bone Regeneration (GBR) are two regenerative procedures which converted
      this goal from a dream to reality. In search of a biocompatible resorbable tissue
      barrier, collagen, being a natural protein and a weak antigen, has attracted much
      interest and became the focus of much intention during the 80's and the 90's. The
      understanding that cross linking of collagen with aldehyde sugars, especially
      ribose, produces collagen which is highly resistant to resorption in vivo led to
      the development of a "natural" Crossed-Linked Collagen Barrier (CB-SX). Animal
      and Human studies have shown that the newly developed membrane is biocompatible,
      remains intact in the tissues 6 months and more, and results in impressive guided
      tissue/bone regeneration. Spontaneous early exposure of the membrane is common
      but the healing potential of the resulted tissue dehiscence is favorable with no
      tendency for bacterial infection. The commercial version of the CB-SX is
      especially suitable for GBR procedures; it is highly recommended that the
      gingival flaps involved will properly be released, will lack tension, and be
      thoroughly sutured.

PMID- 15503981
TI  - [Future therapy strategies for salivary gland impairment].
AB  - Saliva offers many modalities, mainly protecting the oral tissues by maintaining
      a local healthy environment. Several conditions cause salivary gland secretion
      impairment, in which irradiation therapy to the head and neck cancer patients is
      one of the most rigorous, leading to major decline in quality of life. At
      present, conventional therapy provides a limited answer for this situation. In
      the last two decades, several strategies had been proposed to overcome this
      problem. These approaches can be divided into three branches: 1. Preventing
      salivary gland damage before irradiation therapy. 2. Protecting the secretory
      parenchymal tissue during the course of irradiation and, 3. Trying to regenerate
      salivary gland function after irradiation damage has already occurred. These
      attitudes may provide future beneficial modalities to salivary gland dysfunction
      especially in patients were salivary gland function is diminished.

PMID- 15503982
TI  - [Efficacy of treatment with hard and soft occlusal appliance in TMD].
AB  - Temporomandibular disorders (TMD) include clinical disorders involving the
      masticatory muscles, the temporomandibular joints (TMJ) and the adjacent
      structures. TMD was recognized as a main source for pains in the orofacial area,
      which are not caused from dental origin, and is defined by the American Academy
      of Orofascial Pain (AAOP) as a sub-group within the frame of musculoskeletal
      disorders. The main etiology for TMD has not been found yet. The customary
      treatments for this disorder include treatment with occlusal splints,
      physiotherapy, medicaments, behavioral-cognitive treatment, hypnosis, acupuncture
      and surgery that should be considered only if all conservative treatments were
      unsuccessful. Occlusal splint is the most common and efficient treatment for TMD
      patients proved by many studies with a successful rate of 70-90%. The following
      article reviews the different opinions in the treatment of TMD with special
      attention to hard and soft occlusal appliances. Based upon much research, and
      despite the many disagreements regarding its efficacy, the hard splint is a
      customary application which has the most successful outcome in patients who
      suffer from functional disorders of the masticatory system. The stabilization
      splint has an important benefit for being a non-penetrating and reversible
      appliance. However, despite this, the dentist should evaluate the joint or
      muscular problem, and seriously consider the various available treatments before
      deciding to use the appliance as a means of treatment.

PMID- 15503983
TI  - [Pre-septal orbital cellulitis from odentogenic origin--combined surgical and
      endodontic approach: a case report].
AB  - Orbital abscesses are common infectious diseases. The etiology of orbital
      abscesses may vary from common sinusitis in most of the cases, to cocaine
      sniffing. As a result of the proximity to the brain, orbital abscesses may
      complicate to life threatening situations. The infectious process spreads to the
      orbit in several ways: hematogenous, via anatomic spaces in the maxillofacial
      region, direct invasion. The treatment philosophy combines surgical and
      Antibiotic therapy to resolve the acute phase of the disease, followed by
      elimination of the source. The purpose of this paper is to report a case of pre
      septal orbital cellulitis, that was treated surgically combined with endodontic
      therapy. To describe the different subtypes of orbital abscesses, differential
      diagnosis, imaging and treatment options.

PMID- 15503984
TI  - [Smoking--a proven risk factor for periodontal disease?].
AB  - While bacterial dental plaque is widely considered as the etiological risk factor
      for the development of periodontal diseases, numerous publications from recent
      years pointed out the role of environmental factors like smoking as aggravating
      the severity of disease expression. The present paper reviews the updated
      literature linking epidemiologically between the presence of smoking habit and
      disease prevalence in the same population, as well as studies reporting on cell
      toxicity of nicotine and its by-products on gingival cells, negative effect on
      humoral and cell-mediated immune system, enhancement of bacterial plaque
      pathogeneity, and disruption of the wound healing processes. Finally, a negative
      effect is apparent on the supportive stage of the periodontal treatment,
      indicating lasting effect of smoking for years to come following the termination
      of active periodontal treatment.

PMID- 15503985
TI  - [Dentistry--an old or a new profession?].

PMID- 15503986
TI  - Possible closure of a dental school in Israel.

PMID- 15503987
TI  - Scratching an ancient itch: an Eocene bird louse fossil.
AB  - Out of the 30 extant orders of insects, all but one, the parasitic lice (Insecta:
      Phthiraptera), have a confirmed fossil record. Here, we report the discovery of
      what appears to be the first bird louse fossil: an exceptionally well-preserved
      specimen collected from the crater of the Eckfeld maar near Manderscheid,
      Germany. The 44-million-year-old specimen shows close phylogenetic affinities
      with modern feather louse ectoparasites of aquatic birds. Preservation of feather
      remnants in the specimen's foregut confirms its association as a bird
      ectoparasite. Based on a phylogenetic analysis of the specimen and
      palaeoecological data, we suggest that this louse was the parasite of a large
      ancestor to modern Anseriformes (swans, geese and ducks) or Charadriiformes
      (shorebirds). The crown group position of this fossil in the phylogeny of lice
      confirms the group's long coevolutionary history with birds and points to an
      early origin for lice, perhaps inherited from early-feathered theropod dinosaurs.

PMID- 15503988
TI  - Evidence for reproductive isolate selection in Mediterranean orchids: karyotype
      differences compensate for the lack of pollinator specificity.
AB  - Mediterranean orchids of the subtribe Orchidinae are highly diverse and display a
      range of fascinating pollination strategies. Based on observations that orchid
      pollinator relationships are often highly specialized and species specific,
      Darwin and others have argued that selection for different pollinators has been
      the driving force behind the evolutionary diversification of orchids. This may be
      true for orchids that attract different, specialized pollinators that act as
      prezygotic reproductive barriers. It is, however, not clear how closely related
      co-flowering Mediterranean orchids that share pollinators survive the challenge
      of sympatry. We show that species pairs with a generalized pool of pollinators
      have significantly more divergent karyotypes compared with species pairs with
      different pollinators. These results show that karyotype differences that act as
      postzygotic reproductive barriers may have played an important role in the
      evolution of Mediterranean orchid diversity.

PMID- 15503989
TI  - Germline transformation of the butterfly Bicyclus anynana.
AB  - Ecological and evolutionary theory has frequently been inspired by the diversity
      of colour patterns on the wings of butterflies. More recently, these varied
      patterns have also become model systems for studying the evolution of
      developmental mechanisms. A technique that will facilitate our understanding of
      butterfly colour-pattern development is germline transformation. Germline
      transformation permits functional tests of candidate gene products and of cis
      regulatory regions, and provides a means of generating new colour-pattern mutants
      by insertional mutagenesis. We report the successful transformation of the
      African satyrid butterfly Bicyclus anynana with two different transposable
      element vectors, Hermes and piggyBac, each carrying EGFP coding sequences driven
      by the 3XP3 synthetic enhancer that drives gene expression in the eyes. Candidate
      lines identified by screening for EGFP in adult eyes were later confirmed by PCR
      amplification of a fragment of the EGFP coding sequence from genomic DNA.
      Flanking DNA surrounding the insertions was amplified by inverse PCR and
      sequenced. Transformation rates were 5% for piggyBac and 10.2% for Hermes.
      Ultimately, the new data generated by these techniques may permit an integrated
      understanding of the developmental genetics of colour-pattern formation and of
      the ecological and evolutionary processes in which these patterns play a role.

PMID- 15503990
TI  - Correlations between adult mimicry and larval host plants in ithomiine
      butterflies.
AB  - The apparent paradox of multiple coexisting wing pattern mimicry 'rings' in
      tropical butterflies has been explained as a result of microhabitat partitioning
      in adults. However, very few studies have tested this hypothesis. In neotropical
      forests, ithomiine butterflies dominate and display the richest diversity of
      mimicry rings. We show that co-mimetic species occupy the same larval host-plant
      species significantly more often than expected in two out of five communities
      that we surveyed; in one of these, the effect remains significant after
      phylogenetic correction. This relationship is most probably a result of a third
      correlated variable, such as microhabitat. Host-plant microhabitat may constrain
      adult movement, or host-plant choice may depend on butterfly microhabitat
      preferences and mimicry associations. This link between mimicry and host plant
      could help explain some host-plant and mimicry shifts, which have been important
      in the radiation of this speciose tropical group.

PMID- 15503991
TI  - Female facial attractiveness increases during the fertile phase of the menstrual
      cycle.
AB  - The lack of obvious visible manifestations of ovulation in human females,
      compared with the prominent sexual swellings of many primates, has led to the
      idea that human ovulation is concealed. While human ovulation is clearly not
      advertised to the same extent as in some other species, we show here that both
      men and women judge photographs of women's faces that were taken in the fertile
      window of the menstrual cycle as more attractive than photographs taken during
      the luteal phase. This indicates the existence of visible cues to ovulation in
      the human face, and is consistent with similar cyclical changes observed for
      preferences of female body odour. This heightened allure could be an adaptive
      mechanism for raising a female's relative value in the mating market at the time
      in the cycle when the probability of conception is at its highest.

PMID- 15503992
TI  - Four kingdoms on glacier ice: convergent energetic processes boost energy levels
      as temperatures fall.
AB  - A diverse group of glacially obligate organisms coexist on temperate glaciers
      between Washington State and Alaska. A fundamental challenge for these and other
      cold-adapted species is the necessity to maintain an energy flux capable of
      sustaining life at low physiological temperatures. We show here that ice-adapted
      psychrophiles from four kingdoms (Animalia, Eubacteria, Fungi, Protista) respond
      to temperature fluctuations in a similar manner; namely, ATP levels and the total
      adenylate pool increase as temperatures fall (within their viable temperature
      limits, respectively), yet growth rate increases with temperature. By contrast,
      mesophilic representatives of each kingdom respond in an opposite manner (i.e.
      adenylates increase with temperature). These observations suggest that elevated
      adenylate levels in psychrophiles may offset inherent reductions in molecular
      diffusion at low physiological temperatures.

PMID- 15503993
TI  - Direct evidence for predation on trilobites in the Cambrian.
AB  - A fossil arthropod similar to Fuxianhuia and displaying an exceptionally well
      preserved alimentary canal with in situ gut contents is reported from the lower
      Middle Cambrian (ca. 510 Myr ago) of South China. Three-dimensionally preserved,
      paired phosphatic nodules, arranged in series along both sides of the gut and
      containing spherical bacteria, probably represent serial digestive glands. The
      gut is filled with fragments of the eodiscoid trilobite, Pagetia. The well
      developed digestive glands and the fragmentary trilobite remains suggest (i) that
      the arthropod was a durophagous, possibly selective predator, and (ii) that small
      trilobites such as eodiscoids were a major food source in Cambrian marine
      ecosystems. This fossil association augments the small number of previously
      described associations providing more or less direct evidence of predator-prey
      relationships in Cambrian epibenthic communities.

PMID- 15503994
TI  - Penguin-mounted cameras glimpse underwater group behaviour.
AB  - Marine birds and mammals spend most of their lives in the open ocean far from
      human observation, which makes obtaining information about their foraging
      behaviour difficult. Here, we show, by use of a miniaturized digital camera
      system, the first direct evidence (to our knowledge) of underwater group
      behaviour in free-ranging penguins. Penguins swim closely accompanied by other
      bird(s) during 24% of their possible foraging dives. This finding confirms that
      such miniaturized camera technology has broad applicability for advancing our
      knowledge about the previously unknown social interactions of marine animals at
      depth.

PMID- 15503995
TI  - Female intrasexual competition decreases female facial attractiveness.
AB  - Evolutionary theory predicts that female intrasexual competition will occur when
      males of high genetic quality are considered to be a resource. It is probable
      that women compete in terms of attractiveness since this is one of the primary
      criteria used by men when selecting mates. Furthermore, because hormones
      influence the mate-selection process, they may also mediate competition. One
      competitive strategy that women use is derogation--any act intended to decrease a
      rival's perceived value. To investigate intrasexual competition through
      derogation, the influence of oestrogen on women's ratings of female facial
      attractiveness was examined. During periods of high oestrogen, competition, and
      hence derogation, increased, as evidenced by lower ratings of female facial
      attractiveness. By contrast, oestrogen levels did not significantly affect
      ratings of male faces. These findings support the theory of female intrasexual
      competition with respect to attractiveness.

PMID- 15503996
TI  - Diet quality and resource allocation in the zebra finch.
AB  - We investigated the effect of diet quality on resource allocation in zebra
      finches (Taeniopygia guttata) by providing females with a high-quality (HQ) or
      low-quality (LQ) diet for six weeks prior to pairing, and continuing these diets
      during egg laying and chick rearing. Diet treatments were then reversed and the
      experiment repeated. When females laid on the HQ diet, egg mass increased with
      laying order, but the reverse was true on the LQ diet. Females laid significantly
      more male eggs on the LQ diet compared with on the HQ diet. In addition, female
      eggs were more frequent at the end of the clutch when on the HQ diet and at the
      beginning of the clutch when on the LQ diet. These differences in the primary sex
      ratio are in line with predictions from sex allocation theory, since in this
      species females are more vulnerable to nutritional stress than males.

PMID- 15503997
TI  - Do female great reed warblers seek extra-pair fertilizations to avoid inbreeding?
AB  - Females of many species mate with several males. According to a recent
      hypothesis, female promiscuity serves to avoid inbreeding. We tested this
      hypothesis in a polygynous bird, the great reed warbler (Acrocephalus
      arundinaceus), in which extra-pair fertilization, inbreeding and inbreeding
      depression occur. However, the extra-pair males and social males did not differ
      in relatedness to the promiscuous females, nor did the least related males sire
      most of the females' chicks. Thus, contrary to recent findings in some insects,
      birds and reptiles, we found no evidence for inbreeding avoidance among the
      promiscuous females. Instead, female great reed warblers may seek other potential
      benefits when cuckolding, such as good gene effects at particular functional
      genes.

PMID- 15503998
TI  - Turtle and mammal penis designs are anatomically convergent.
AB  - Males in many modern amniote taxa have a hydraulic penis that inflates for
      copulation. Hydraulic skeletons are typically reinforced with inextensible
      fibres; the specific arrangement of the fibres within the skeleton determines
      whether it is flexible or resists bending. I show that the hydraulic skeleton in
      the turtle penis is reinforced by an axial orthogonal array of collagen fibres.
      This microanatomy is evolutionarily convergent with that of mammalian penises,
      and implies that there is a limited number of mechanical designs for an
      inflatable structure with high bending stiffness.

PMID- 15503999
TI  - How well does second-to-fourth-digit ratio in hands correlate with other
      indications of masculinity in males?
AB  - Low second-to-fourth-digit (2D:4D) ratios in hands have previously been used as a
      proxy for prenatal testosterone levels. Moreover, it has recently been suggested
      that prenatal testosterone levels may direct future masculinization. If true,
      2D:4D ratios should negatively correlate with traits in males that are developed
      and maintained by testosterone at puberty such as facial and body masculinity and
      testes volume. We failed to find significant correlations between 2D:4D ratios
      and these traits.

PMID- 15504000
TI  - Possible role of female discrimination against 'redundant' males in the evolution
      of colour pattern polymorphism in guppies.
AB  - Multiple paternity of offspring can result from active preferences on the part of
      females or sexual harassment by males. We examined sexual responses of female
      guppies to a previous mate versus a novel male (experiment 1) or to a male with a
      colour pattern similar to that of the previous mate versus a novel male
      (experiment 2). Females showed significantly more sexual responses to courtship
      by novel males than to previous mates in experiment 1 or to males that resembled
      previous mates in experiment 2. These results suggest that females discriminate
      actively against previous mates, and extend this discrimination to males with
      similar colour patterns to previous mates. This could lead to negative frequency
      dependent sexual selection against common colour patterns (a 'redundant male
      effect'), which could contribute to the maintenance of the extraordinarily high
      levels of genetic polymorphism in guppy colour patterns.

PMID- 15504001
TI  - Whooping cough metapopulation dynamics in tropical conditions: disease
      persistence and impact of vaccination.
AB  - Recent insights in compiling metapopulation models and infectious disease
      dynamics have enabled a better understanding of spatial and temporal persistence
      of diseases. The concept of the critical community size (CCS) has been developed
      with major consideration on analyses of whooping cough and measles dynamics from
      temperate countries for which large datasets are available. However, few studies
      have questioned the generality of CCS curves for other regions, i.e. tropical
      areas, mainly because data are very sparse. This work constitutes, to our
      knowledge, the first study of whooping cough persistence in a tropical area, in a
      rural part of Senegal (Western Africa) where the population has been followed for
      20 years. In this small community, the CCS is not reached even if we observe CCS
      like curves showing persistence increasing with population size. In addition, our
      analysis supports the idea that vaccination has impacted the spatiotemporal
      dynamics and persistence of the disease. These findings suggest the need for more
      comparative analyses of spatio-temporal data series from a wide range of
      contrasted countries, for example developed and developing nations, so as to have
      a better understanding of vaccination effects on disease dynamics and
      persistence.

PMID- 15504002
TI  - Sexy sons: a dead end for cytoplasmic genes.
AB  - Critics of sexual conflict theory argue that females may gain a net reproductive
      benefit from mating with manipulative males because the direct costs that they
      suffer may be offset by the production of sexy, i.e. manipulative, sons. However,
      this exclusive focus on nuclear gene effects represents an incomplete view of
      female fitness. Females differ fundamentally from males in transmitting not only
      nuclear genes but also a wide range of cytoplasmic genetic elements (CGEs) that
      can have profound effects, from male killing to influencing development of the
      nervous system and cognitive ability. Maternal transmission of CGEs has two major
      implications for sexual selection. First, the evolution of male fitness traits,
      such as sperm competitive ability, may be constrained because response to
      selection on mitochondrial genomes can occur only through the female line.
      Second, CGEs bear the direct costs of male manipulation but gain no indirect
      benefits when females produce sexy sons. This should result in perpetual
      antagonistic coevolution between nuclear genes involved in male manipulation and
      CGEs that promote female resistance to male sexually selected traits. Explicit
      consideration of the consequences of selection acting on CGEs is therefore
      necessary for a better understanding of the relationship between sexual selection
      and sexual conflict.

PMID- 15504003
TI  - Tragedy of the commons in Melipona bees.
AB  - In human society selfish use of common resources can lead to disaster, a
      situation known as the 'tragedy of the commons' (TOC). Although a TOC is usually
      prevented by coercion, theory predicts that close kinship ties can also favour
      reduced exploitation. We test this prediction using data on a TOC occurring in
      Melipona bee societies.

PMID- 15504004
TI  - A theory of modern cultural shifts and meltdowns.
AB  - Many cultural attributes such as adornment, language slang, mannerisms and
      rituals are thought to have little or no influence on individual survival and
      reproduction, functioning rather as markers of cultural identity that promote
      group cohesion. Here, I show that if cultural markers are under weak selection
      and subject to loss or substitution, then the breakdown of cultural cohesiveness
      may proceed without stabilizing reactions until many or most of a culture's
      identifiers are forever lost. This may culminate in a 'cultural meltdown',
      whereby the culture is caught in a vortex of ever-decreasing membership and
      insufficient selection against the accumulation of unfamiliar markers. In
      progressively altering the topology of communication from diffusion to
      broadcasting, globalization may be both accelerating the erosion of cultural
      identities and amplifying dominance behaviours above their normal adaptive
      levels.

PMID- 15504005
TI  - Patterns and coevolutionary consequences of repeated brood parasitism.
AB  - The absence of adaptive host responses to virulent parasites and pathogens is
      paradoxical. We explored the theoretical possibility that the evolution of
      antiparasitic egg-ejection strategies was delayed by avian hosts' lifetime
      experiences with brood parasitism. An analytical model indicated that individual
      hosts' repeated exposure to parasitism decreased the relative benefits of
      learning-based rejecter strategies when parasitism was particularly costly.
      Because brood parasitic brown-headed cowbirds (Molothrus ater) and their hosts
      are typically philopatric across breeding attempts, spatially and temporally non
      random patterns of parasitism may contribute to low levels of observed egg
      ejection by vulnerable cowbird hosts. In support, we found that in three
      populations of two host species individual females experienced repeated cowbird
      parasitism during their lifetimes. We propose that repeated parasitism
      contributes to counterintuitive patterns of coevolutionary dynamics in spatially
      structured host-parasite populations.

PMID- 15504006
TI  - Molecular sexing of prey remains permits a test of sex-biased predation in a
      wintering population of western sandpipers.
AB  - Population sex ratios in monogamous birds are often male biased. One factor that
      can affect population sex ratios is sex-biased predation. However, most estimates
      of sex-biased predation in birds have focused on species with obvious sexual
      colour dimorphism or body size dimorphism. Data on sexually monomorphic birds are
      generally lacking. In the present study, we adopt a PCR-based sexing procedure to
      help test for sex-biased predation in a wintering population of western
      sandpipers (Calidris mauri), a shorebird that shows only subtle sexual size
      dimorphism. Specifically, by comparing the a priori determined sex ratio of live
      birds wintering at a site in western Mexico to the molecular estimate obtained
      from depredated birds at this same site, we were able to perform a population
      specific test for sex bias in predator-induced mortality. The proportion of
      females estimated from living (ca. 25%) versus dead (ca. 24%) individuals was in
      fact not significantly different, indicating that the strong male bias in this
      population is not due to differential predation. However, molecular sexing of
      prey remains is a hitherto unexploited test of sex-biased predation in birds, and
      is potentially applicable to any species for which prey remains can be gathered.
      We discuss our results in the context of alternate ecological hypotheses for
      population sex biases.

PMID- 15504007
TI  - Forelimb proportions and the evolutionary radiation of Neornithes.
AB  - Analysis of a comprehensive dataset demonstrates that the brachial index (BI =
      humerus length/ulna length) of modern birds (Neornithes) varies significantly
      between clades at all taxonomic levels, yet is strongly correlated with recent
      phylogenetic hypotheses. Variance in BI at the infraclass level is low, but
      increases rapidly during the proposed major radiation of neornithines in the
      Palaeocene and Eocene. Although a BI of greater than 1 is primitive for
      Neornithes, more basal groups of Mesozoic birds (Confuciusornithidae and some
      members of the diverse Enantiornithidae) had BIs comparable with those of
      'higher' modern clades. It is possible that occupation of ecological niches by
      these Mesozoic clades precluded the divergence of some groups of neornithines
      until after the Cretaceous-Tertiary boundary. We suggest that with further
      analysis and data collection the relationships between flight behaviour, ecology
      and BI can be determined. Hence, BI may provide a useful tool for characterizing
      the ecology of fossil birds.

PMID- 15504008
TI  - Assessment and assortment: how fishes use local and global cues to choose which
      school to go to.
AB  - Animals that live in groups are known preferentially to associate with
      phenotypically similar individuals. Despite this, groups of mixed phenotypic
      composition are the norm rather than the exception in several systems in the wild
      and this, combined with the large sizes of some animal groups, makes accurate
      global assessment by a choosing individual more difficult. In this study, we
      investigated the role of local and global information in mediating shoal-choice
      decisions in three-spined sticklebacks (Gasterosteus aculeatus) by manipulating
      the positions and phenotypes of stimulus fish in relation to a focal fish. Focal
      fish were able to assess globally mixed shoals composed of individuals of
      different body-length classes, preferring to associate with shoals where the
      majority phenotype matched their own. When local cues were manipulated this
      preference disappeared, although overall shoal composition remaining constant.
      Finally, if both stimulus shoals had the same overall composition but differed in
      their local cues, then the focus fish chose according to which local fish was of
      matching body length. These findings indicate that both local and global
      information play an important role in mediating assessment and shoal choice in
      fishes.

PMID- 15504009
TI  - Do positive interactions increase with abiotic stress? A test from a semi-arid
      steppe.
AB  - Theoretical models predict that the relative importance of facilitation and
      competition may vary inversely across gradients of abiotic stress. However, these
      predictions have not been thoroughly tested in the field, especially in semi-arid
      environments. In this study, we evaluated how the net effect of the tussock grass
      Stipa tenacissima on the shrub Pistacia lentiscus varied across a gradient of
      abiotic stress in semi-arid Mediterranean steppes. We fitted the relationship
      between accumulated rainfall and the relative neighbour index (our measures of
      abiotic stress and of the net effect of S. tenacissima on P. lentiscus,
      respectively), which varied across this gradient, to a quadratic model.
      Competitive interactions dominated at both extremes of the gradient. Our results
      do not support established theory. Instead, they suggest that a shift from
      facilitation to competition under high abiotic stress conditions is likely to
      occur when the levels of the most limiting resource are so low that the benefits
      provided by the facilitator cannot overcome its own resource uptake.

PMID- 15504010
TI  - Using the functional response to determine the nature of unequal interference
      among foragers.
AB  - The food intake rate of foragers may be reduced as a result of interference,
      which may be asymmetric among individuals and occur as a result of intimidation,
      direct aggression or filtering. It is important to distinguish among these types
      of interference, because each can have different consequences for individuals,
      foraging groups and populations. We demonstrate the application of the functional
      response as a tool for distinguishing between types of interference. We apply the
      approach to juvenile Atlantic salmon and show that stepwise elimination of
      interference types is possible from regression analyses of functional responses,
      identifying filtering as the only effective type of interference in the study
      environment.

PMID- 15504011
TI  - Predation risk and longevity influence variation in fitness of female roe deer
      (Capreolus capreolus L.).
AB  - We studied the effects of population density, red fox predation risk, individual
      body mass and longevity on female fitness in a free-ranging roe deer population.
      During the study, population density varied from 9.3 to 36.1 deer km(-2), and red
      fox abundance varied strongly over years owing to a sarcoptic mange outbreak. In
      support of our predictions, long-lived females had higher fitness than short
      lived ones. Further, fortunate female roe deer that gave birth in years of low
      red fox abundance attained much higher fitness than those that gave birth in
      years of high red fox abundance. Longevity and predation risk explained more than
      half the variation in fitness observed among roe deer females. As a possible
      effect of small sample size, we found no effect of female body mass or population
      density at birth. Our study demonstrates that predation risk, a component of
      environmental stochasticity, may prevent directional selection even when
      phenotypic quality influences individual fitness.

PMID- 15504012
TI  - Inclusive fitness benefits of scent-marking predators.
AB  - Because relatedness is high and dispersal is limited, one would expect to see
      higher levels of altruistic behaviour among clonal organisms than among animals
      of lesser relatedness. Enigmatically, however, parthenogenetic aphids do not emit
      alarm signals when a predator first enters a colony but only after being
      captured. Here, we report that an aphid smearing alarm pheromone directly onto a
      predator decreases the predation risk for clone-mates as the predator continues
      to search for additional prey. Adult multicoloured Asian ladybird beetles,
      Harmonia axyridis, daubed with alarm pheromone caused a greater proportion of
      aphids to drop off a plant and escape predation than did predators lacking
      pheromone droplets. Thus, along with direct fitness benefits of individual
      protection, aphid alarm signalling behaviour may have evolved through inclusive
      fitness benefits of protecting clone-mates by scent-marking predators.

PMID- 15504013
TI  - Lateralization of tool use in New Caledonian crows (Corvus moneduloides).
AB  - We studied laterality of tool use in 10 captive New Caledonian (NC) crows (Corvus
      moneduloides). All subjects showed near-exclusive individual laterality, but
      there was no overall bias in either direction (five were left-lateralized and
      five were right-lateralized). This is consistent with results in non-human
      primates, which show strong individual lateralization for tool use (but not for
      other activities), and also with observations of four wild NC crows by Rutledge &
      Hunt. Jointly, these results contrast with observations that the crows have a
      population-level bias for manufacturing tools from the left edges of Pandanus sp.
      leaves, and suggest that the manufacture and use of tools in this species may
      have different neural underpinnings.

PMID- 15504014
TI  - Nutritional bias as a new mode of adjusting sex allocation.
AB  - Sex biases in the allocation of resources to offspring occur in a broad range of
      taxa. Parents have been shown to achieve such biases either by producing
      numerically more of one sex or by providing the individuals of one sex with a
      greater quantity of resources. In addition, skews in allocation could occur if
      the offspring of one sex receive resources of higher quality (greater nutritional
      or energetic value by weight or volume), although this mode of adjustment has, to
      our knowledge, never been demonstrated. We compared the types of prey and the
      metabolizable energy provisioned to male and female nestlings in one of the most
      sexually size dimorphic of all birds, the brown songlark, Cinclorhamphus
      cruralis. Within broods, we found that males not only received more prey than
      their smaller sisters, but also prey of apparently higher quality. This dietary
      disparity could result either from mothers actively discriminating between the
      sexes when providing prey or from competition among siblings. We suggest that sex
      differences in offspring diet quality may occur in a wide range of other taxa and
      function as an additional mechanism of sex allocation adjustment.

PMID- 15504015
TI  - Growth hormone transgenic salmon pay for growth potential with increased
      predation mortality.
AB  - Recent advances in gene technology have been applied to create fast-growing
      transgenic fish, which are of great commercial interest owing to their potential
      to shorten production cycles and increase food production. However, there is
      growing concern and speculation over the impact that escaped growth hormone (GH)
      transgenic fish may have on the natural environment. To predict these risks it is
      crucial to obtain empirical data on the relative fitness of transgenic and non
      transgenic fish under nature-like conditions. Using landscaped stream aquaria
      with live food and predators, we show that the predation mortality of newly
      hatched GH-transgenic coho salmon fry (Oncorhynchus kisutch) is much higher than
      in non-transgenic conspecifics, and that this difference is amplified when food
      abundance decreases. The growth rate of transgenic and non-transgenic fish is
      similar at high food levels, whereas transgenic fish grow more slowly than non
      transgenic fish when food abundance is reduced. Our results suggest that the
      fitness of young GH-transgenic coho salmon in the wild will be determined by both
      predation pressure and food availability.

PMID- 15504016
TI  - Random drift and large shifts in popularity of dog breeds.
AB  - A simple model of random copying among individuals, similar to the population
      genetic model of random drift, can predict the variability in the popularity of
      cultural variants. Here, we show that random drift also explains a biologically
      relevant cultural phenomenon--changes in the distributions of popularity of dog
      breeds in the United States in each of the past 50 years. There are, however,
      interesting deviations from the model that involve large changes in the
      popularity of certain breeds. By identifying meaningful departures from our null
      model, we show how it can serve as a foundation for studying culture change
      quantitatively, using the tools of population genetics.

PMID- 15504017
TI  - Exploring the consequences of postmating-prezygotic interactions between the
      sexes.
AB  - The role of male-female interactions in the divergence of postmating-prezygotic
      reproductive traits has recently focused on sexual conflict as the selective
      force. While an association between mating costs and benefits suggests that
      antagonistic interactions may be important, a mosaic of processes may actually
      mediate the evolutionary dynamics of postmating-prezygotic interactions. Our
      study examines the ecological relevance of mating effects on females. We test
      this critical but often overlooked assumption in desert Drosophila, where the
      species' ecology provides a framework for evaluating the evolutionary
      implications of such mating consequences. We show that mating has a profound
      impact on an ecologically critical character--desiccation resistance. To explore
      what selective factors might underlie the observed population differences in
      mating effects, we test whether trends in the data match predictions based on the
      species' ecology. While these preliminary data are consistent with the
      expectation that the mating benefits are positively correlated with environmental
      conditions, further examination reveals an additional unanticipated association
      with the reproductive environment. This unexpected association challenges
      existing assumptions regarding the forces driving divergence of traits involved
      in mating.

PMID- 15504018
TI  - Birds sacrifice oxidative protection for reproduction.
AB  - Oxidative metabolism has reactive oxygen species (ROS) as unavoidable by
      products, and the damage ROS inflicts on DNA, proteins and lipids is considered
      to be a major agent of senescence. Increasing reproductive effort accelerates
      senescence, but whether reproductive effort is increased at the expense of
      protection against oxidative damage has not yet been tested. We manipulated
      reproductive effort in zebra finches through brood size manipulation and measured
      the activity of two major antioxidant enzymes (superoxide dismutase (SOD) and
      glutathione peroxidase (GPx)) in the pectoral muscle after 19-20 days of brood
      rearing. Oxidative stress is reflected by the balance between oxidative
      protection and ROS exposure, and we therefore scaled SOD and GPx activity to
      daily energy expenditure (DEE) as an index of ROS production. SOD and GPx
      activity decreased with increasing brood size by 28% and 24%, respectively. This
      effect was identical in the two sexes, but arose in different ways: males did not
      change their DEE, but had lower absolute enzyme activity, and females increased
      their DEE, but did not change absolute enzyme activity. This result suggests that
      senescence acceleration by increased reproductive effort is at least in part
      mediated by oxidative stress.

PMID- 15504019
TI  - Polynomial epidemics and clustering in contact networks.
AB  - It is widely known that the spread of the human immunodeficiency virus was slower
      than exponential in several populations, even at the very beginning of the
      epidemic. We show that this implies a significant reduction in the effective
      reproductive rate of the epidemic, and describe a general mechanism, related to
      the clustering properties of the disease transmission network, that is capable of
      explaining this reduction. Our considerations provide what is, to our knowledge,
      a new angle on polynomial epidemic processes, and may have implications for the
      choice of strategy against such epidemics.

PMID- 15504020
TI  - Falling palm fronds structure amazonian rainforest sapling communities.
AB  - The senescence and loss of photosynthetic and support structures is a nearly
      universal aspect of tree life history, and can be a major source of disturbance
      in forest understoreys, but the ability of falling canopy debris in determining
      the stature and composition of understorey communities seems not to have been
      documented. In this study, we show that senescent fronds of the palm Iriartea
      deltoidea cause substantial disturbance in tropical forest sapling communities.
      This disturbance influences the species composition of the canopy and subcanopy
      by acting as an ecological filter, favouring sapling species with characteristics
      conducive to recovery after physical damage. The scale of this dominance suggests
      that falling I. deltoidea debris may be influencing sapling community structure
      and species composition in Amazonian rainforests over very large spatial scales.

PMID- 15504021
TI  - Detectability and content as opposing signal characteristics in fruits.
AB  - Although often associated with consumers, fruit colours have rarely been assessed
      as signals. Here, we investigate the signal principles of 'detectability' and
      'content' in bird-dispersed fruits. We determined detectability as the contrast
      between fruit and background and signal 'content' by correlating fruit colours
      and compounds. Red and black, the most common fruit colours globally, contrast
      more against background than other colours but do not indicate compounds. In
      other colours, 60% of the variation in long- to shortwave light correlated with
      protein, tannin and carbohydrate content. Because macronutrients stimulated fruit
      removal, while phenols, but not tannins, deterred it, signalling these
      macronutrients probably increases seed dispersal. Phenolic content was not
      signalled because it would reduce plants' fitness. Signalling tannins might be
      directed towards fruit pests rather than dispersers. In conclusion, plants may
      employ differential signalling strategies matching conspicuous signals in red and
      black fruits while other colours signal fruit quality. The latter implies that
      nutrient quality and fruit defence are communicated visually.

PMID- 15504022
TI  - Nitrogen versus carbon use in prokaryotic genomes and proteomes.
AB  - There is growing recognition that the elemental composition of genomes and
      proteins can be related to resource limitation. We examine the possibility that
      the elemental composition of nucleic acids and the amino acids (and proteins)
      they encode are correlated. We report a positive association between the
      stoichiometric ratio of N/C content of individual amino acids and their codons.
      Potentially, this is an outcome of chemical interactions between amino acids and
      anticodons that influenced the evolution of the genetic code. We also find a
      strong, positive relationship between N/C values of whole genomes and proteomes,
      across 94 prokaryotic species. This relationship is part of a spectrum in
      nitrogen versus carbon use across genomes and proteomes, which is correlated with
      genomic GC content. GC content is correlated positively with average nitrogen
      use, and negatively with average carbon use, across both genomes and proteomes.

PMID- 15504023
TI  - Novel phylogenetic relationships of the enigmatic brevicipitine and
      scaphiophrynine toads as revealed by sequences from the nuclear Rag-1 gene.
AB  - Owing to a general paucity of characters and an apparently high level of
      homoplasy, the systematics of frogs have remained disputed. A phylogeny based on
      the single-copy nuclear Rag-1 gene revealed unexpected placements of
      scaphiophrynine and brevicipitine toads. The former have usually been considered
      as sister group to all other extant microhylids or are even classified as a
      separate family. Their basal position among microhylids was weakly indicated in
      our analysis; but they clearly are part of a strongly supported clade composed of
      representatives from five other microhylid subfamilies. By contrast, the
      brevicipitines, a group that hitherto was unanimously considered to belong to the
      Microhylidae, were highly divergent and placed as a sister group to the
      arthroleptoid clade. These novel phylogenetic placements are best reflected by a
      classificatory status of the Scaphiophryninae as a subfamily of the Microhylidae,
      whereas the brevicipitines may merit recognition as a distinct family. Our
      findings seem to corroborate a high degree of morphological homoplasy in frogs
      and suggest that even highly derived morphological states, such as the
      hydrostatic tongue of microhylids, hemisotids and brevicipitines, may be subject
      to convergent evolution, parallelism or character reversal.

PMID- 15504024
TI  - Effects of the C4'-oxidized abasic site on replication in Escherichia coli. An
      unusually large deletion is induced by a small lesion.
AB  - The C4'-oxidized abasic site (C4-AP) is produced in DNA as a result of oxidative
      stress by a variety of agents. For instance, the lesion accounts for
      approximately 40% of the DNA damage produced by the antitumor antibiotic
      bleomycin. The effect of C4-AP on DNA replication in Escherichia coli was
      determined using the restriction endonuclease and postlabeling (REAP) method.
      Three-nucleotide deletion products are the sole products observed following
      replication of plasmids containing C4-AP under SOS conditions in wild-type cells.
      Full-length products are formed in varying amounts depending upon the local
      sequence in wild-type cells under non-SOS-induced conditions. The "A-rule" is
      followed for the formation of substitution products. C4-AP is the first example
      of a DNA lesion that produces significant levels of three-nucleotide deletions in
      a variety of sequence contexts. Experiments carried out in cells lacking specific
      polymerases reveal that formation of three-nucleotide deletion products results
      from a coordinated effort involving pol II and pol IV. This is the first example
      in which these SOS inducible polymerases are shown to work in concert during
      lesion bypass. Three-nucleotide deletions are not observed during the replication
      of other abasic lesions, and are rarely produced by bulky adducts. The effect of
      C4-AP on DNA replication suggests a significant role for this lesion in the
      cytotoxicity of bleomycin. Formation of the C4-AP lesion may also be responsible
      for the formation of mutant proteins containing single-amino acid deletions that
      exhibit altered phenotypes.

PMID- 15504025
TI  - Binding mechanism of nonspecific lipid transfer proteins and their role in plant
      defense.
AB  - Plant nonspecific lipid transfer proteins (nsLTPs) are small basic proteins that
      transport phospholipids between membranes. On the basis of molecular mass, nsLTPs
      are subdivided into nsLTP1 and nsLTP2. NsLTPs are all helical proteins stabilized
      by four conserved disulfide bonds. The existence of an internal hydrophobic
      cavity, running through the molecule, is a typical characteristic of nsLTPs that
      serves as the binding site for lipid-like substrates. NsLTPs are known to
      participate in plant defense, but the exact mechanism of their antimicrobial
      action against fungi or bacteria is still unclear. To trigger plant defense
      responses, a receptor at the plant surface needs to recognize the complex of a
      fungal protein (elicitin) and ergosterol. NsLTPs share high structural
      similarities with elicitin and need to be associated with a hydrophobic ligand to
      stimulate a defense response. In this study, binding of sterol molecules with
      rice nsLTPs is analyzed using various biophysical methods. NsLTP2 can accommodate
      a planar sterol molecule, but nsLTP1 binds only linear lipid molecules. Although
      the hydrophobic cavity of rice nsLTP2 is smaller than that of rice nsLTP1, it is
      flexible enough to accommodate the voluminous sterol molecule. The dissociation
      constant for the nsLTP2/cholesterol complex is approximately 71.21 microM as
      measured by H/D exchange and mass spectroscopic detection. Schematic models of
      the nsLTP complex structure give interesting clues about the reason for
      differential binding modes. Comparisons of NMR spectra of the sterol/rice nsLTP2
      complex and free nsLTP2 revealed the residues involved in binding.

PMID- 15504026
TI  - Protein functional cycle viewed at atomic resolution: conformational change and
      mobility in nitrophorin 4 as a function of pH and NO binding.
AB  - The blood-sucking insect Rhodnius prolixus uses nitrophorin 4, a heme protein, to
      deliver nitric oxide (NO) to a victim, causing vasodilation and improved feeding.
      Binding of NO occurs at a ferric heme and is modulated by pH. NO binding at lower
      pH induces a large conformational change involving loops A-B and G-H that leads
      to distal pocket desolvation and protection of the nitrosyl heme complex. We have
      determined the crystal structures of Rhodnius nitrophorin 4 to ultrahigh
      resolution in four functional states: +/-NO at pH = 7.4 and +/-NO at pH = 5.6.
      The structure with NO at pH 7.4 (1.08 A) is newly determined while the other
      complexes have been modeled to resolutions much greater than previously reported
      (1.0-0.85 A). The ultrahigh resolution allowed us to resolve multiple conformers
      in binding-site loops, leading to a detailed description of the dynamics involved
      with storing NO in the insect salivary gland at low pH, and releasing NO in
      response to the increased pH of a victim's tissue. Strikingly, features for both
      the "open" and "closed" conformers exist under all conditions, suggesting that
      the flexible loops can transition with relative ease between conformational
      states. Yet, release of NO from rNP4 is much slower than found for other ferric
      heme proteins. The structures suggest that highly mobile loops can limit
      diffusion of diatomic molecules into and out of a protein cavity, a result with
      implications for the role of protein dynamics in function.

PMID- 15504027
TI  - Binding, proteolytic, and crystallographic analyses of mutations at the protease
      inhibitor interface of the subtilisin BPN'/chymotrypsin inhibitor 2 complex.
AB  - A series of mutants of chymotrypsin inhibitor 2 (CI2), at residues that interact
      with the inhibited enzyme subtilisin BPN', were studied to determine the relative
      importance of intermolecular contacts on either side of the scissile bond.
      Mutants were tested for inhibition of subtilisin, rates of hydrolysis by
      subtilisin, and ability to acylate subtilisin. Additionally, crystal structures
      of the mutant CI2 complexes with subtilisin were obtained. Ordered water
      molecules were found to play an important role in inhibitor recognition, and
      features of the crystal structures, in combination with biochemical data, support
      a transition-state stabilization role for the P(1) residue in subtilisin
      catalysis. Consistent with the proposed mechanism of inhibition, in which rapid
      acylation is followed by religation, leaving-group contacts with the enzyme were
      found to be more critical determinants of inhibition than acylating-group
      contacts in the mutants studied here.

PMID- 15504028
TI  - DNA binding of an organic dppz-based intercalator.
AB  - An improved synthesis of a water-soluble derivative of dipyrido[3,2-a:2',3'
      c]phenazine (dppz) is reported. The structures of both dppz and the cation
      ethylene-bipyridyldiylium-phenazine dinitrate [[1][(PF(6))(2)]] have been
      obtained via X-ray crystallography. Metal complex derivatives of dppz are very
      well studied. However, using the water soluble [1][(NO(3))(2)], the nature of the
      interaction of a simple dppz unit with duplex DNA has been investigated for the
      first time. In both organic solvents and water, 1 displays unstructured
      luminescence, assigned to an intramolecular charge transfer. The emission is
      quenched on binding to natural and synthetic duplex DNA, including
      poly(dA).poly(dT). A variety of techniques reveal that the cation binds to DNA
      with an affinity comparable to those of many metal dppz complexes, via an
      intercalative binding mode.

PMID- 15504029
TI  - Phosphonoformate: a minimal transition state analogue inhibitor of the fosfomycin
      resistance protein, FosA.
AB  - Fosfomycin [(1R,2S)-epoxypropylphosphonic acid] is a simple phosphonate found to
      have antibacterial activity against both Gram-positive and Gram-negative
      microorganisms. Early resistance to the clinical use of the antibiotic was linked
      to a plasmid-encoded resistance protein, FosA, that catalyzes the addition of
      glutathione to the oxirane ring, rendering the antibiotic inactive. Subsequent
      studies led to the discovery of a genomically encoded homologue in the pathogen
      Pseudomonas aeruginosa. The proteins are Mn(II)-dependent enzymes where the metal
      is proposed to act as a Lewis acid stabilizing the negative charge that develops
      on the oxirane oxygen in the transition state. Several simple phosphonates,
      including the antiviral compound phosphonoformate (K(i) = 0.4 +/- 0.1 microM,
      K(d) approximately 0.2 microM), are shown to be inhibitors of FosA. The crystal
      structure of FosA from P. aeruginosa with phosphonoformate bound in the active
      site has been determined at 0.95 A resolution and reveals that the inhibitor
      forms a five-coordinate complex with the Mn(II) center with a geometry similar to
      that proposed for the transition state of the reaction. Binding studies show that
      phosphonoformate has a near-diffusion-controlled on rate (k(on) approximately
      10(7)-10(8) M(-1) s(-1)) and an off rate (k(off) = 5 s(-1)) that is slower than
      that for fosfomycin (k(off) = 30 s(-1)). Taken together, these data suggest that
      the FosA-catalyzed reaction has a very early transition state and
      phosphonoformate acts as a minimal transition state analogue inhibitor.

PMID- 15504030
TI  - Spectroscopic and functional characterization of T state hemoglobin conformations
      encapsulated in silica gels.
AB  - Oxygen binding curves of sol-gel-encapsulated deoxy human adult hemoglobin (HbA)
      have previously revealed two distinct noncooperative populations with oxygen
      binding affinities approximately 1000 and 100 times lower than that of the high
      affinity R state. The two populations which have been termed the low-affinity
      (LA) and high-affinity (HA) T states can be selectively stabilized using two
      different encapsulation protocols for deoxy-HbA. The present study seeks to
      understand the factors giving rise to these different affinity states. Visible
      and UV resonance Raman spectroscopies are used to characterize the conformational
      properties of both the deoxy and deoxy-turned-carbonmonoxy (CO) derivatives of
      HbA derived from the two encapsulation protocols. The geminate and bimolecular
      recombination of CO to the photodissociated CO derivatives is used to
      characterize the functional properties of the slowly evolving encapsulated
      populations. The results show that the initial deoxy-HbA populations are
      conformationally indistinguishable with respect to encapsulation protocol. The
      addition of CO to sol-gel-encapsulated deoxy-HbA triggers a detectable
      progression of conformational and functional changes. Visible resonance Raman
      spectra of the CO photoproduct reveal a progression of changes of the iron
      proximal histidine stretching frequencies: 215, 222, 227, and 230 cm(-1). The low
      and high values correspond to the initial deoxy T state and liganded R (R(2))
      state species, respectively. The 222 and 227 cm(-1) species are generated using
      encapsulation protocols that give rise to what are termed the LA and HA T states,
      respectively. The UV resonance Raman spectra of these and related species
      indicate that the progression from deoxy T to LA to HA is associated with a
      progressive loosening of T state constraints within the hinge and switch regions
      of the alpha(1)beta(2) interface. The time scale for the progression is
      determined by a balance between the ligation-initiated evolution toward high
      affinity conformations and factors such as allosteric effectors, gel matrix, and
      added glycerol that slow ligand-binding-induced relaxation. Thus, it appears that
      the encapsulation protocol-dependent rate of ligand-binding-induced relaxation
      determines the functional properties of the initially encapsulated deoxy-HbA
      population.

PMID- 15504031
TI  - Stereoselective hydrogen abstraction by galactose oxidase.
AB  - The fungal enzyme galactose oxidase is a radical copper oxidase that catalyzes
      the oxidation of a broad range of primary alcohols to aldehydes. Previous
      mechanistic studies have revealed a large substrate deuterium kinetic isotope
      effect on galactose oxidase turnover whose magnitude varies systematically over a
      series of substituted benzyl alcohols, reflecting a change in the character of
      the transition state for substrate oxidation. In this work, these detailed
      mechanistic studies have been extended using a series of stereospecifically
      monodeuterated substrates, including 1-O-methyl-alpha-D-galactose as well as
      unsubstituted benzyl alcohol and 3- and 4-methoxy and 4-nitrobenzyl derivatives.
      Synthesis of all of these substrates was based on oxidation of the alpha,alpha'
      dideuterated alcohol to the corresponding (2)H-labeled aldehyde, followed by
      asymmetric hydroboration using alpha-pinene/9-BBN reagents to form the
      stereoisomeric alcohols. Products from enzymatic oxidation of each of these
      substrates were characterized by mass spectrometry to quantitatively evaluate the
      substrate dependence of the stereoselectivity of the catalytic reaction. For all
      of these substrates, the selectivity for pro-S hydrogen abstraction was at least
      95%. This selectivity appears to be a direct consequence of constraints imposed
      by the enzyme on the orientation of substrates bearing a branched beta-carbon.
      Steady state analysis of kinetic isotope effects on V/K has resolved individual
      contributions from primary and alpha-secondary kinetic isotope effects in the
      reaction, providing a test for the involvement of an electron transfer redox
      equilibrium in the oxidation process. Multiple isotope effect measurements
      utilizing simultaneous labeling of the substrate and solvent have contributed to
      refinement of the relation between proton transfer and hydrogen atom transfer
      steps in substrate oxidation.

PMID- 15504032
TI  - Tyrosine phosphorylation of caveolin-2 at residue 27: differences in the spatial
      and temporal behavior of phospho-Cav-2 (pY19 and pY27).
AB  - Caveolin-2 is an accessory molecule and the binding partner of caveolin-1.
      Previously, we showed that c-Src expression leads to the tyrosine phosphorylation
      of Cav-2 at position 19. To further investigate the tyrosine phosphorylation of
      Cav-2, we have now generated a novel phospho-specific antibody directed against
      phospho-Cav-2 (pY27). Here, we show that Cav-2 is phosphorylated at both
      tyrosines 19 and 27. We reconstituted this phosphorylation event by recombinantly
      coexpressing c-Src and Cav-2. We generated a series of Cav-2 constructs harboring
      the mutation of each tyrosine to alanine, singly or in combination, i.e., Cav-2
      Y19A, Y27A, and Y19A/Y27A. Recombinant expression of these mutants in Cos-7 cells
      demonstrated that neither tyrosine is the unique phosphorylation site, and that
      double mutation of tyrosines 19 and 27 to alanine abrogates Cav-2 tyrosine
      phosphorylation. Immunofluorescence analysis of NIH 3T3 cells revealed that the
      two tyrosine-phosphorylated forms of Cav-2 exhibited some distinct properties.
      Phospho-Cav-2 (pY19) is concentrated at cell edges and at cell-cell contacts,
      whereas phospho-Cav-2 (pY27) is distributed in a dotlike pattern throughout the
      cell surface and cytoplasm. Further functional analysis revealed that tyrosine
      phosphorylation of Cav-2 has no effect on its targeting to lipid rafts, but
      clearly disrupts the hetero-oligomerization of Cav-2 with Cav-1. In an attempt to
      identify upstream mediators, we investigated Cav-2 tyrosine phosphorylation in an
      endogenous setting. We found that in A431 cells, EGF stimulation is sufficient to
      induce Cav-2 phosphorylation at tyrosines 19 and 27. However, the behavior of the
      two phosphorylated forms of Cav-2 diverges upon EGF stimulation. First, phospho
      Cav-2 (pY19) and phospho-Cav-2 (pY27) display different localization patterns. In
      addition, the temporal response to EGF stimulation appears to be different. Cav-2
      is phosphorylated at tyrosine 19 in a rapid and transient fashion, whereas
      phosphorylation at tyrosine 27 is sustained over time. Three SH2 domain
      containing proteins, c-Src, Nck, and Ras-GAP, were found to associate with Cav-2
      in a phosphorylation-dependent manner. However, phosphorylation at tyrosine 27
      appears to be more critical than phosphorylation at tyrosine 19 for this binding
      to occur. Taken together, these results suggest that, in addition to the common
      characteristics that these two sites appear to share, phospho-Cav-2 (pY19) and
      phospho-Cav-2 (pY27) may each possess a set of unique functional roles.

PMID- 15504033
TI  - Transmission of force and displacement within the myosin molecule.
AB  - Myosin is a repetitive impeller of actin, using its catalysis of ATP hydrolysis
      to derive repeatedly the required free energy decrements. In each impulsion,
      changes at the myosin active site are transmitted through a series of structural
      elements to the myosin propeller (lever arm), almost 5 nm away. While the nature
      of transmission through most elements is evident, that through the so-called
      converter is not. To investigate how the converter changes linear displacement
      into rotation, we tested (one at a time) the effect of two Phe residue mutations
      (at 721 and 775) in the converter on the overall function of a heavy meromyosin
      (or subfragment 1) system, after first showing by observing kinetic behaviors
      that neither mutation affects other elements in the transmission. Using three
      tests (direct movement of the lever arm, activity in a motility assay with actin
      filaments, and direct force measurement of lever arm function), we found that
      these mutations affected only movements of the converter and the lever arm. From
      interpreting our observations in terms of the structure of the converter, we
      deduce that the linear-rotational transformation in the converter is mediated by
      a little machine (two Phe residues linked to a Gly) within a machine.

PMID- 15504034
TI  - Three-dimensional structure of the R115E mutant of T4-bacteriophage 2'
      deoxycytidylate deaminase.
AB  - 2'-Deoxycytidylate deaminase (dCD) converts deoxycytidine 5'-monophosphate (dCMP)
      to deoxyuridine 5'-monophosphate and is a major supplier of the substrate for
      thymidylate synthase, an important enzyme in DNA synthesis and a major target for
      cancer chemotherapy. Wild-type dCD is allosterically regulated by the end
      products of its metabolic pathway, deoxycytidine 5'-triphosphate and
      deoxythymidine 5'-triphosphate, which act as an activator and an inhibitor,
      respectively. The first crystal structure of a dCD, in the form of the R115E
      mutant of the T4-bacteriophage enzyme complexed with the active site inhibitor
      pyrimidin-2-one deoxyribotide, has been determined at 2.2 A resolution. This
      mutant of dCD is active, even in the absence of the allosteric regulators. The
      molecular topology of dCD is related to that of cytidine deaminase (CDA) but with
      modifications for formation of the binding site for the phosphate group of dCMP.
      The enzyme has a zinc ion-based mechanism that is similar to that of CDA. A
      second zinc ion that is present in bacteriophage dCD, but absent in mammalian dCD
      and CDA, is important for the structural integrity of the enzyme and for the
      binding of the phosphate group of the substrate or inhibitor. Although the R115E
      mutant of dCD is a dimer in solution, it crystallizes as a hexamer, mimicking the
      natural state of the wild-type enzyme. Residues 112 and 115, which are known to
      be important for the binding of the allosteric regulators, are found in a pocket
      that is at the intersubunit interfaces in the hexamer but distant from the
      substrate-binding site. The substrate-binding site is composed of residues from a
      single protein molecule and is sequestered in a deep groove. This groove is
      located at the outer surface of the hexamer but ends at the subunit interface
      that also includes residue 115. It is proposed that the absence of subunit
      interactions at this interface in the dimeric R115E mutant renders the substrate
      binding site accessible. In contrast, for the wild-type enzyme, binding of dCTP
      induces an allosteric effect that affects the subunit interactions and results in
      an increase in the accessibility of the binding site.

PMID- 15504035
TI  - Expression, purification, and biochemical characterization of the
      antiinflammatory tristetraprolin: a zinc-dependent mRNA binding protein affected
      by posttranslational modifications.
AB  - Tristetraprolin (TTP) is a hyperphosphorylated protein that destabilizes mRNA by
      binding to an AU-rich element (ARE). Mice deficient in TTP develop a severe
      inflammatory syndrome. The biochemical properties of TTP have not been adequately
      characterized, due to the difficulties in protein purification and lack of a high
      titer antiserum. Full-length human TTP was expressed in human HEK293 cells and
      purified to at least 70% homogeneity. The purified protein was free of endogenous
      ARE binding activity, and was used for investigating its size, zinc dependency,
      and binding kinetics for tumor necrosis factor alpha mRNA ARE. A high-titer
      rabbit antiserum was raised against the MBP-hTTP fusion protein expressed in
      Escherichia coli. Cellular localization studies of the transfected cells
      indicated that approximately 80% of the expressed TTP was in the cytosol, with
      20% in the nuclei. TTP from both locations bound to the ARE and formed similar
      complexes. The purified TTP was shown to be intact by N-terminal His-tag
      purification, C-terminal peptide sequencing, and mass spectrometry analysis.
      Results from size exclusion chromatography are consistent with the predominant
      form of active TTP being a tetramer. TTP's ARE binding activity was increased by
      10 microM Zn(2+). The half-maximal binding of TTP from HEK293 cells was
      approximately 30 nM in assays containing 10 nM ARE. This value was about twice
      that of TTP from E. coli. TTP from HEK293 cells was highly phosphorylated, and
      its electrophoretic mobility was increased by alkaline phosphatase treatment and
      somewhat by T271A mutation, but not by PNGase F or S186A mutation. The gel
      mobility of TTP from E. coli was decreased by in vitro phosphorylation with
      p42/ERK2 and p38 mitogen-activated protein kinases. These results suggest that
      TTP's zinc-dependent ARE binding affinity is reduced by half by posttranslational
      modifications, mainly by phosphorylation but not by glycosylation, in mammalian
      cells. The results support a model in which each subunit of the TTP tetramer
      binds to one of the five overlapping UUAUUUAUU sequences of the ARE, resulting in
      a stable TTP-ARE complex.

PMID- 15504036
TI  - Dynamics in the U6 RNA intramolecular stem-loop: a base flipping conformational
      change.
AB  - The U6 RNA intramolecular stem-loop (ISL) structure is an essential component of
      the spliceosome and binds a metal ion required for pre-messenger RNA splicing.
      The metal binding internal loop region of the stem contains a partially
      protonated C67-(+)A79 base pair (pK(a) = 6.5) and an unpaired U80 nucleotide that
      is stacked within the helix at pH 7.0. Here, we determine that protonation occurs
      with an exchange lifetime of approximately 20 micros and report the solution
      structures of the U6 ISL at pH 5.7. The differences between pH 5.7 and 7.0
      structures reveal that the pH change significantly alters the RNA conformation.
      At lower pH, U80 is flipped out into the major groove. Base flipping involves a
      purine stacking interaction of flanking nucleotides, inversion of the sugar
      pucker 5' to the flipped base, and phosphodiester backbone rearrangement.
      Analysis of residual dipolar couplings as a function of pH indicates that base
      flipping is not restricted to a local conformational change. Rather, base
      flipping alters the alignment of the upper and lower helices. The alternative
      conformations of the U6 ISL reveal striking structural similarities with both the
      NMR and crystal structures of domain 5 of self-splicing group II introns. These
      structures suggest that base flipping at an essential metal binding site is a
      conserved feature of the splicing machinery for both the spliceosome and group II
      self-splicing introns.

PMID- 15504037
TI  - Role of charged residues of pharaonis phoborhodopsin (sensory rhodopsin II) in
      its interaction with the transducer protein.
AB  - pharaonis phoborhodopsin (ppR; also called pharaonis sensory rhodopsin II,
      NpSRII) is a receptor for negative phototaxis in Natronomonas (Natronobacterium)
      pharaonis. In membranes, it forms a 2:2 complex with its transducer protein,
      pHtrII, which transmits light signals into the cytoplasmic space through protein
      protein interactions. We previously found that a specific deprotonated carboxyl
      of ppR or pHtrII strengthens their binding [Sudo, Y., et al. (2002) Biophys. J.
      83, 427-432]. In this study we aim to identify this carboxyl group. Since the
      D75N mutant has only one photointermediate (ppR(O)(-)(like)) whose existence
      spans the millisecond time range, the analysis of its decay rate is simple. We
      prepared various D75N mutants such as D75N/D214N, D75N/K157Q/R162Q/R164Q
      (D75N/3Gln), D75N/D193N, and D75N/D193E, among which only D75N/D193N did not show
      pH dependence with regard to the ppR(O)(-)(like) decay rate and K(D) value for
      binding, implying that the carboxyl group in question is from Asp-193. The pK(a)
      of this group decreased to below 2 when a complex was formed. Therefore, we
      conclude that Asp-193(p)()(pR) is connected to the distant transducer-ppR binding
      surface via hydrogen bonds, thereby modulating its pK(a). In addition, we discuss
      the importance of Arg-162(p)()(pR) with respect to the binding activity.

PMID- 15504038
TI  - Mechanism for ordered receptor binding by human prolactin.
AB  - Prolactin, a lactogenic hormone, binds to two prolactin receptors sequentially,
      the first receptor binding at site 1 of the hormone followed by the second
      receptor binding at site 2. We have investigated the mechanism by which human
      prolactin (hPRL) binds the extracellular domain of the human prolactin receptor
      (hPRLbp) using surface plasmon resonance (SPR) technology. We have covalently
      coupled hPRL to the SPR chip surface via coupling chemistries that reside in and
      block either site 1 or site 2. Equilibrium binding experiments using saturating
      hPRLbp concentrations show that site 2 receptor binding is dependent on site 1
      receptor occupancy. In contrast, site 1 binding is independent of site 2
      occupancy. Thus, sites 1 and 2 are functionally coupled, site 1 binding inducing
      the functional organization of site 2. Site 2 of hPRL does not have a measurable
      binding affinity prior to hPRLbp binding at site 1. After site 1 receptor
      binding, site 2 affinity is increased to values approaching that of site 1.
      Corruption of either site 1 or site 2 by mutagenesis is consistent with a
      functional coupling of sites 1 and 2. Fluorescence resonance energy transfer
      (FRET) experiments indicate that receptor binding at site 1 induces a
      conformation change in the hormone. These data support an "induced-fit" model for
      prolactin receptor binding where binding of the first receptor to hPRL induces a
      conformation change in the hormone creating the second receptor-binding site.

PMID- 15504039
TI  - Isoleucine 69 and valine 325 form a specificity pocket in human muscle creatine
      kinase.
AB  - Creatine kinase (CK) catalyzes the reversible phosphorylation of creatine by ATP.
      From a structural perspective, the enzyme utilizes two flexible loop regions to
      sequester and position the substrates for catalysis. There has been debate over
      the specific roles of the flexible loops in substrate specificity and catalysis
      in CK and other related phosphagen kinases. In CK, two hydrophobic loop residues,
      I69 and V325, make contacts with the N-methyl group of creatine. In this study,
      we report the alteration of the substrate specificity of CK through the
      mutagenesis of V325. The V325 to glutamate mutation results in a more than 100
      fold preference for glycocyamine, while mutation of V325 to alanine results in a
      slight preference of the enzyme for cyclocreatine (1-carboxymethyl-2
      iminoimidazolidine). This study enhances our understanding of how the active
      sites of phosphagen kinases have evolved to recognize their respective substrates
      and catalyze their reactions.

PMID- 15504040
TI  - Folding and domain-domain interactions of the chaperone PapD measured by 19F NMR.
AB  - The folding of the two-domain bacterial chaperone PapD has been studied to
      develop an understanding of the relationship between individual domain folding
      and the formation of domain-domain interactions. PapD contains six phenylalanine
      residues, four in the N-terminal domain and two in the C-terminal domain. To
      examine the folding properties of PapD, the protein was both uniformly and site
      specifically labeled with p-fluoro-phenylalanine ((19)F-Phe) for (19)F NMR
      studies, in conjunction with those of circular dichroism and fluorescence. In
      equilibrium denaturation experiments monitored by (19)F NMR, the loss of (19)F
      Phe native intensity for both the N- and C-terminal domains shows the same
      dependence on urea concentration. For the N-terminal domain the loss of native
      intensity is mirrored by the appearance of separate denatured resonances. For the
      C-terminal domain, which contains residues Phe 168 and Phe 205, intermediate as
      well as denatured resonances appear. These intermediate resonances persist at
      denaturant concentrations well beyond the loss of native resonance intensity and
      appear in kinetic refolding (19)F NMR experiments. In double-jump (19)F NMR
      experiments in which proline isomerization does not affect the refolding
      kinetics, the formation of domain-domain interactions is fast if the protein is
      denatured for only a short time. However, with increasing time of denaturation
      the native intensities of the N- and C-terminal domains decrease, and the
      denatured resonances of the N-terminal domain and the intermediate resonances of
      the C-terminal domain accumulate. The rate of loss of the N-terminal domain
      resonances is consistent with a cis to trans isomerization process, indicating
      that from an equilibrium denatured state the slow refolding of PapD is due to the
      trans to cis isomerization of one or both of the N-terminal cis proline residues.
      The data indicate that both the N- and C-terminal domains must fold into a native
      conformation prior to the formation of domain-domain interactions.

PMID- 15504041
TI  - Low-temperature electron transfer in photosystem II: a tyrosyl radical and
      semiquinone charge pair.
AB  - The states induced by illumination at 7 K in the oxygen-evolving enzyme (PSII)
      from Thermosynechococcus elongatus were studied by EPR. In the S(0) and S(1)
      redox states, two g approximately 2 EPR signals, a split signal and a g = 2.03
      signal, respectively, were generated by illumination with visible light. These
      signals were comparable to those already reported in plant PSII in terms of their
      g value, shape, and stability at low temperatures. We report that the formation
      and decay of these signals correlate with EPR signals from the semiquinone of the
      first quinone electron acceptor, Q(A)(-). The light-induced EPR signals from
      oxidized side-path electron donors (Cyt b(559), Car, and Chl(Z)) were also
      measured, and from these and the signals from Q(A)(-), estimates were made of the
      proportion of centers involved in the formation of the g approximately 2 signals
      (approximately 50% in S(0) and 40% in S(1)). Comparisons with the signals
      generated in plant PSII indicated approximately similar yields for the S(0) split
      signal. A single laser flash at 7 K induced more than 75% of the maximum split
      and g = 2.03 EPR signal observed by continuous illumination, with no detectable
      oxidation of side-path donors. The matching electron acceptor side reactions, the
      high quantum yield, and the relatively large proportion of centers involved
      support earlier suggestions that the state being monitored is Tyr(Z)(*)Q(A)(-),
      with the g approximately 2 EPR signals arising from Tyr(Z)(*) interacting
      magnetically with the Mn complex. The current picture of the photochemical
      reactions occurring in PSII at low temperatures is reassessed.

PMID- 15504042
TI  - Factors that determine Ca2+ sensitivity of photoreceptor guanylyl cyclase.
      Kinetic analysis of the interaction between the Ca2+-bound and the Ca2+-free
      guanylyl cyclase activating proteins (GCAPs) and recombinant photoreceptor
      guanylyl cyclase 1 (RetGC-1).
AB  - We explored the possibility that, in the regulation of an effector enzyme by a
      Ca(2+)-sensor protein, the actual Ca(2+) sensitivity of the effector enzyme can
      be determined not only by the affinity of the Ca(2+)-sensor protein for Ca(2+)
      but also by the relative affinities of its Ca(2+)-bound versus Ca(2+)-free form
      for the effector enzyme. As a model, we used Ca(2+)-sensitive activation of
      photoreceptor guanylyl cyclase (RetGC-1) by guanylyl cyclase activating proteins
      (GCAPs). A substitution Arg(838)Ser in RetGC-1 found in human patients with cone
      rod dystrophy is known to shift the Ca(2+) sensitivity of RetGC-1 regulation by
      GCAP-1 to a higher Ca(2+) range. We find that at physiological concentrations of
      Mg(2+) this mutation increases the free Ca(2+) concentration required for half
      maximal inhibition of the cyclase from 0.27 to 0.61 microM. Similar to rod outer
      segment cyclase, Ca(2+) sensitivity of recombinant RetGC-1 is strongly affected
      by Mg(2+), but the shift in Ca(2+) sensitivity for the R838S mutant relative to
      the wild type is Mg(2+)-independent. We determined the apparent affinity of the
      wild-type and the mutant RetGC-1 for both Ca(2+)-bound and Ca(2+)-free GCAP-1 and
      found that the net shift in Ca(2+) sensitivity of the R838S RetGC-1 observed in
      vitro can arise predominantly from the change in the affinity of the mutant
      cyclase for the Ca(2+)-free versus Ca(2+)-loaded GCAP-1. Our findings confirm
      that the dynamic range for RetGC regulation by Ca(2+)/GCAP is determined by both
      the affinity of GCAP for Ca(2+) and relative affinities of the effector enzyme
      for the Ca(2+)-free versus Ca(2+)-loaded GCAP.

PMID- 15504043
TI  - Glycolipid transfer protein mediated transfer of glycosphingolipids between
      membranes: a model for action based on kinetic and thermodynamic analyses.
AB  - Glycolipid transfer protein (GLTP) catalyzes the intermembrane transfer of lipids
      that have sugars beta-linked to either diacylglycerol or ceramide backbones,
      including simple glycosphingolipids (GSLs) and gangliosides. The present study
      provides a quantitative understanding of GLTP action involving bilayer vesicles
      that have high and low curvature stress, i.e., small and large unilamellar
      vesicles (SUVs and LUVs). When the GSL intervesicular transfer was monitored in
      real time using an established fluorescence resonance energy approach, the
      initial GSL transfer rates (v(0)) and net transfer equilibrium (K(eq)) were
      determined for GLTP-mediated transfer from SUVs and LUVs over the temperature
      range of 30-44 degrees C. v(0) exhibited a linear dependence with respect to
      varying GLTP concentrations (0-143 nM range) in SUVs and LUVs, suggesting a first
      order dependence on the GLTP bulk concentration. Thermodynamic parameters
      associated with the GLTP-GSL transition-state complex and GSL net transfer were
      determined from linear Arrhenius and van't Hoff plots, respectively. Although
      initial transfer rates were lower for LUVs than for SUVs, the activation energy
      barriers were higher for LUVs, while the Gibbs's free energy of the transition
      states were similar. The formation of a transition-state complex was
      predominantly enthalpy driven, whereas the net transfer of GSLs was mainly
      entropy driven. The rate-limiting step for GLTP action appeared to be the surface
      processes leading to the GLTP-GSL complex formation and release associated with a
      shuttle/carrier mode of action. Because surface processes leading to the GLTP-GSL
      complex formation were limiting for GLTP action with SUVs and LUVs, it was
      concluded that GLTP is likely to be a valuable tool to probe and manipulate GSL
      environments in membranes.

PMID- 15504044
TI  - Control of Hap1-DNA site recognition through the interplay of multiple distinct
      intermolecular interactions.
AB  - Hap1 belongs to the Zn(2)Cys(6) zinc binuclear cluster family of transcription
      factors that typically bind as dimers to symmetric DNA sites containing two CGG
      triplets separated by spacer DNA. The cluster domain binds CGG while an adjoining
      C-terminal linker and dimerization helix specifies the length of spacer DNA
      recognized. Hap1 is unusual in binding a direct repeat of CGG triplets, in
      contacting a TA in the spacer DNA, and in making direct dimer contacts between
      its cluster domains. Binding of Hap1 fragments to different DNA sites was tested
      to determine how these interactions control Hap1-DNA recognition. The spacer TA
      contacts were found to facilitate monomer binding of Hap1 to a single CGG. When
      the spacer-binding residues were deleted, binding was still specific for the
      direct repeat but was much weaker and appeared to require dimerization. When the
      dimerization helix and all subsequent C-terminal residues were deleted, the
      remaining linker, cluster domain, and spacer-binding residues still dimerized on
      DNA. The energy of this dimerization was comparable to that of the Hap1-spacer TA
      interaction. Moving the TA from the spacer to a position following the second CGG
      maintained Hap1 monomer binding but greatly weakened dimerization. This suggested
      that binding a TA after the second CGG triplet required a geometry that impaired
      dimerization with a Hap1 molecule on the first CGG. The geometric restraints for
      optimal TA binding and dimerization thus drive Hap1 selectivity for CGG direct
      repeat sites that contain an asymmetrically positioned spacer TA following the
      first CGG triplet.

PMID- 15504046
TI  - Solid-state NMR investigation of the selective disruption of lipid membranes by
      protegrin-1.
AB  - The interaction of a beta-hairpin antimicrobial peptide, protegrin-1 (PG-1), with
      various lipid membranes is investigated by (31)P, (2)H, and (13)C solid-state
      NMR. Mixed lipid bilayers containing anionic lipids and cholesterol are used to
      mimic the bacterial and mammalian cell membranes, respectively. (31)P and (2)H
      spectra of macroscopically oriented samples show that PG-1 induces the formation
      of an isotropic phase in anionic bilayers containing phosphatidylglycerol. Two
      dimensional (31)P exchange experiments indicate that these isotropic lipids are
      significantly separate from the residual oriented lamellar bilayers, ruling out
      toroidal pores as the cause for the isotropic signal. (1)H spin diffusion
      experiments show that PG-1 is not exclusively bound to the isotropic phase but is
      also present in the residual oriented lamellar bilayers. This dynamic and
      morphological heterogeneity of the anionic membranes induced by PG-1 is supported
      by the fact that (13)C T(2) relaxation times measured under cross polarization
      and direct polarization conditions differ significantly. In contrast to the
      anionic membrane, the zwitterionic phosphatidylcholine (PC) membrane does not
      form an isotropic phase in the presence of PG-1 but shows significant
      orientational disorder. The addition of cholesterol to the PC bilayer
      significantly reduces this orientational disorder. The (13)C T(2) relaxation
      times of the PC lipids in the presence of both cholesterol and PG-1 suggest that
      the peptide may decrease the dynamic heterogeneity of the cholesterol-containing
      membrane. The observed selective interaction of PG-1 with different lipid
      membranes is consistent with its biological function and may be caused by its
      strong cationic and amphipathic structure.

PMID- 15504045
TI  - Pre-steady-state kinetic studies of the fidelity of human DNA polymerase mu.
AB  - DNA polymerase mu (Polmu), an X-family DNA polymerase, is preferentially
      expressed in secondary lymphoid tissues with yet unknown physiological functions.
      In this study, Polmu was overexpressed in Escherichia coli and purified to
      homogeneity. The purified enzyme had a lifetime of <20 min at 37 degrees C, but
      was stable for over 3 h at 25 degrees C in an optimized reaction buffer. The
      fidelity of human Polmu was thus determined using pre-steady-state kinetic
      analysis of the incorporation of single nucleotides into undamaged DNA 21/41-mer
      substrates at 25 degrees C. Single-turnover saturation kinetics for all 16
      possible deoxynucleotide (dNTP) incorporations and for four matched
      ribonucleotide (rNTP) incorporations were measured under conditions where Polmu
      was in molar excess over DNA. The polymerization rate (k(p)), binding affinity
      (K(d)), and substrate specificity (k(p)/K(d)) are 0.006-0.076 s(-1), 0.35-1.8
      microM, and (8-64) x10(-3) microM(-1) s(-1), respectively, for matched incoming
      dNTPs, (2-30) x 10(-5) s(-1), 7.3-135 microM, and (4-61) x 10(-7) microM(-1) s(
      1), respectively, for mismatched incoming dNTPs, and (2-73) x 10(-4) s(-1), 45
      302 microM, and (7-1300) x 10(-7) microM(-1) s(-1), respectively, for matched
      incoming rNTPs. The overall fidelity of Polmu was estimated to be in the range of
      10(-3)-10(-5) for both dNTP and rNTP incorporations and was sequence-independent.
      The sugar selectivity, defined as the substrate specificity ratio of a matched
      dNTP versus a matched rNTP, was measured to be in the range of 492-10959. In
      addition to a slow and distributive DNA polymerase activity, Polmu was identified
      to possess a weak strand-displacement activity. The potential biological roles of
      Polmu are discussed.

PMID- 15504047
TI  - Dynamic motions of CD39 transmembrane domains regulate and are regulated by the
      enzymatic active site.
AB  - The two transmembrane domains flanking the active site of CD39 regulate its
      activity, but little is known about the structural and dynamic features
      underlying their importance. Here we use a disulfide crosslinking strategy to
      examine transmembrane helix interactions and dynamics and to correlate these
      features with activity and substrate binding. We find strong intrasubunit TM1-TM2
      interactions, as well as TM1-TM1' and TM2-TM2' interactions between dimer
      subunits, near the extracellular side of the membrane but only weak interactions
      near the cytoplasmic end. The specific helix faces that constitute each interface
      are highly flexible, indicating a significant degree of rotational mobility
      within the packed structure. Analysis of activity after locking the helices in
      various orientations via disulfide bonds suggests that not only the arrangement
      but also the ability of the helices to move relative to each other is crucial for
      enzyme function. Helix mobility is in turn modulated by substrate binding. These
      results suggest that rather than playing a static structural role to support an
      optimal active site conformation, the transmembrane domains undergo dynamic
      motions that underlie their functional relationship with the active site.

PMID- 15504048
TI  - Kinetically robust monomeric protein from a hyperthermophile.
AB  - Equilibrium and kinetic studies were carried out under denaturation conditions to
      clarify the energetic features of the high stability of a monomeric protein,
      ribonuclease HII, from a hyperthermophile, Thermococcus kodakaraensis (Tk-RNase
      HII). Guanidine hydrochloride (GdnHCl)-induced unfolding and refolding were
      measured with circular dichroism at 220 nm, and heat-induced denaturation was
      studied with differential scanning calorimetry. Both GdnHCl- and heat-induced
      denaturation are very reversible. It was difficult to obtain the equilibrated
      unfolding curve of Tk-RNase HII below 40 degrees C, because of the remarkably
      slow unfolding. The two-state unfolding and refolding reactions attained
      equilibrium at 50 degrees C after 2 weeks. The Gibbs energy change of GdnHCl
      induced unfolding (DeltaG(H(2)O)) at 50 degrees C was 43.6 kJ mol(-1). The
      denaturation temperature in the DSC measurement shifted as a function of the scan
      rate; the denaturation temperature at a scan rate of 90 degrees C h(-1) was
      higher than at a scan rate of 5 degrees C h(-1). The unfolding and refolding
      kinetics of Tk-RNase HII were approximated as a first-order reaction. The ln k(u)
      and ln k(r) values depended linearly on the denaturant concentration between 10
      and 50 degrees C. The DeltaG(H(2)O) value obtained from the rate constant in
      water using the two-state model at 50 degrees C, 44.5 kJ mol(-1), was coincident
      with that from the equilibrium study, 43.6 kJ mol(-1), suggesting the two-state
      folding of Tk-RNase HII. The values for the rate constant in water of the
      unfolding for Tk-RNase HII were much smaller than those of E. coli RNase HI and
      Thermus thermophilus RNase HI, which has a denaturation temperature similar to
      that of Tk-RNase HII. In contrast, little difference was observed in the
      refolding rates among these proteins. These results indicate that the
      stabilization mechanism of monomeric protein from a hyperthermophile, Tk-RNase
      HII, with reversible two-state folding is characterized by remarkably slow
      unfolding.

PMID- 15504049
TI  - Micromechanical analysis of the binding of DNA-bending proteins HMGB1, NHP6A, and
      HU reveals their ability to form highly stable DNA-protein complexes.
AB  - The mechanical response generated by binding of the nonspecific DNA-bending
      proteins HMGB1, NHP6A, and HU to single tethered 48.5 kb lambda-DNA molecules is
      investigated using DNA micromanipulation. As protein concentration is increased,
      the force needed to extend the DNA molecule increases, due to its compaction by
      protein-generated bending. Most significantly, we find that for each of HMGB1,
      NHP6A, and HU there is a well-defined protein concentration, not far above the
      binding threshold, above which the proteins do not spontaneously dissociate. In
      this regime, the amount of protein bound to the DNA, as assayed by the degree to
      which the DNA is compacted, is unperturbed either by replacing the surrounding
      protein solution with protein-free buffer or by straightening of the molecule by
      applied force. Thus, the stability of the protein-DNA complexes formed is
      dependent on the protein concentration during the binding. HU is distinguished by
      a switch to a DNA-stiffening function at the protein concentration where the
      formation of highly stable complexes occurs. Finally, introduction of competitor
      DNA fragments into the surrounding solution disassembles the stable DNA complexes
      with HMGB1, NHP6A, and HU within seconds. Since spontaneous dissociation of
      protein does not occur on a time scale of hours, we conclude that this rapid
      protein exchange in the presence of competitor DNA must occur only via "direct"
      DNA-DNA contact. We therefore observe that protein transport along DNA by direct
      transfers occurs even for proteins such as NHP6A and HU that have only one DNA
      binding domain.

PMID- 15504050
TI  - Ca2+-calmodulin regulates fesselin-induced actin polymerization.
AB  - Fesselin is a proline-rich actin-binding protein that was isolated from avian
      smooth muscle. Fesselin bundles actin and accelerates actin polymerization by
      facilitating nucleation. We now show that this polymerization of actin can be
      regulated by Ca(2+)-calmodulin. Fesselin was shown to bind to immobilized
      calmodulin in the presence of Ca(2+). The fesselin-calmodulin interaction was
      confirmed by a Ca(2+)-dependent increase in 2-(4-maleimidoanilino)naphthalene-6
      sulfonic acid (MIANS) fluorescence upon addition of fesselin to MIANS-labeled
      wheat germ calmodulin. The affinity was estimated to be approximately 10(9) M(
      1). The affinity of Ca(2+)-calmodulin to the fesselin F-actin complex was
      approximately 10(8) M(-1). Calmodulin binding to fesselin appeared to be
      functionally significant. In the presence of fesselin and calmodulin, the
      polymerization of actin was Ca(2+)-dependent. Ca(2+)-free calmodulin either had
      no effect or enhanced the ability of fesselin to accelerate actin polymerization.
      Ca(2+)-calmodulin not only reversed the stimulatory effect of fesselin but
      reduced the rate of polymerization below that observed in the absence of
      fesselin. While Ca(2+)-calmodulin had a large effect on the interaction of
      fesselin with G-actin, the effect on F-actin was small. Neither the binding of
      fesselin to F-actin nor the subsequent bundling of F-actin was greatly affected
      by Ca(2+)-calmodulin. Fesselin may function as an actin-polymerizing factor that
      is regulated by Ca(2+) levels.

PMID- 15504051
TI  - Spinal cord neuropathology in human West Nile virus infection.

PMID- 15504053
TI  - On the origin of hepatic fibrosis.

PMID- 15504055
TI  - Bilirubin proficiency testing using specimens containing unconjugated bilirubin
      and human serum: results of a College of American Pathologists study.
AB  - CONTEXT: Specimens of the College of American Pathologists Neonatal Bilirubin and
      Chemistry surveys are inadequate for evaluating the performance of clinical
      laboratories in measuring serum bilirubin because they exhibit strong matrix
      interference. Recently published data indicate that at least 1 major clinical
      analyzer provided inaccurate bilirubin values for Neonatal Bilirubin Survey
      specimens. The composition of the specimens, bovine serum enriched with
      ditaurobilirubin, was responsible for the erroneous results. OBJECTIVE: This
      article evaluates the performance of major clinical analyzers using a survey
      specimen free of matrix interference. DESIGN: A human serum-based specimen
      enriched solely with unconjugated bilirubin was included in the 2003 Neonatal
      Bilirubin and Chemistry surveys. Its bilirubin concentration (19.4 mg/dL [332
      micromol/L]) was determined by the reference method for total bilirubin. RESULTS:
      The coefficients of variation for the 4 major clinical analyzers (Dimension,
      Hitachi, Synchron, and Vitros) ranged from 1.9% to 3.7%. When compared to the
      bilirubin value measured by the reference method, mean bilirubin values of the 4
      major clinical analyzers and College of American Pathologists (CAP) All Data
      (which refers to the grand mean and overall coefficient of variation of all
      method principles, all instruments according to CAP terminology) ranged from 
      3.5% to 5.1%. Direct bilirubin results from most field methods showed good
      specificity overall. CONCLUSION: Human serum-based survey specimens, having their
      bilirubin concentrations determined by the reference method, should be included
      as frequently as feasible in the Neonatal Bilirubin Survey. Such specimens may be
      used by instrument manufacturers as standards for calibrating bilirubin methods
      and for assigning values to calibrators provided to instrument users. A
      substantial improvement in bilirubin measurements due to the reduction of
      systematic error is expected.

PMID- 15504056
TI  - Bethesda 2001 implementation and reporting rates: 2003 practices of participants
      in the College of American Pathologists Interlaboratory Comparison Program in
      Cervicovaginal Cytology.
AB  - CONTEXT: The 2001 Bethesda System for the reporting of cervical cytology
      specimens and the use of new liquid-based and human papillomavirus testing
      technologies have led to changes in cervical cytology reporting practices.
      OBJECTIVES: To analyze current laboratory reporting practices using Bethesda 2001
      terminology and to compare results with previous survey data from 1996. DESIGN:
      Questionnaire survey mailed to 1751 laboratories in mid-2003. PARTICIPANTS:
      Laboratories enrolled in the College of American Pathologists Interlaboratory
      Comparison Program in Cervicovaginal Cytology. RESULTS: Of the 759 responding
      laboratories, most (85.5%) had implemented Bethesda 2001 terminology, and the
      majority had adopted major changes, such as elimination of the benign cellular
      changes category and the satisfactory but limited category. The median reporting
      rate for low-grade squamous intraepithelial lesion was 2.1%, compared to a 1996
      median rate of 1.6%, but the increase was confined to liquid-based preparations.
      Reporting rates for high-grade squamous intraepithelial lesion (median, 0.5%) and
      atypical squamous cells (ASC) had changed little. Most ASC cases were
      subclassified as "undetermined significance" (median, 3.9%) with ASC, cannot
      exclude high-grade SIL accounting for a minority (median, 0.2%). The median ratio
      of ASC to squamous intraepithelial lesions and carcinomas (SIL+) was 1.4 and was
      lower than the 1996 median ratio of 2.0. Median reporting rates for squamous
      abnormalities for 2002 were noted to be significantly higher for liquid-based
      preparations than for conventional smears, while median ASC/SIL+ ratios were
      lower. Most laboratories offer human papillomavirus testing, but almost half
      (47%) of laboratories do not know the percentage of positive testing results in
      patients with ASC. CONCLUSIONS: Most laboratories have implemented Bethesda 2001
      terminology. New criteria and liquid-based methods have led to an increase in low
      grade squamous intraepithelial lesion reporting rates and a decrease in ASC/ SIL+
      ratios when compared with 1996 data. Liquid-based preparations have higher median
      squamous intraepithelial lesion rates and lower ASC/SIL+ ratios than conventional
      smears.

PMID- 15504057
TI  - The immunology of fibrogenesis in alcoholic liver disease.
AB  - CONTEXT: Alcoholic liver disease in humans frequently leads to cirrhosis.
      Experimental models of hepatic fibrogenesis are available, but extrapolation of
      those findings to human ethanol-induced liver injury is difficult. Hepatic
      ethanol-induced fibrosis in humans has often been studied in relatively small
      patient populations. During the past decade, several animal models and human
      studies have attributed fibrogenesis in the liver to the role played by
      hepatocytes, Kupffer cells, endothelial cells, and especially stellate cells.
      OBJECTIVE: To determine the contribution of the main liver cell types to ethanol
      induced fibrogenesis. For that purpose, we studied the expression of the
      following immunologic parameters: smooth muscle-specific alpha actin (SMSA),
      CD68, CD34, transforming growth factor beta1, intercellular adhesion molecule 1,
      and collagen types 1 and 3. The Dako LSAB+ kit (peroxidase method) was used.
      DESIGN: We recently studied a large cohort of patients with alcoholic liver
      disease in France. In this cohort, we found 87 cases in which liver biopsies
      revealed only pericentral injury with nonpathologic portal areas. We compared
      cases in which the portal areas were nonpathologic with 324 patients in whom
      staging ranged from F0 to F3. Patients with cirrhosis (F4) were excluded from
      evaluation. To stage fibrosis, we used the METAVIR system. Furthermore, we
      selected 40 cases in which the biopsies measured at least 25 mm in length for
      further histochemical evaluation. Ten additional normal cases from our archives
      were used as controls. We divided this patient population into the following 5
      groups of 10 patients each: group 1A, F0 with steatosis; group 1B, F0 without
      steatosis; group 2, F0 to F1, central injury; group 3, F3, fibrosis with multiple
      septa; and group 4, nonpathologic livers (controls). RESULTS: Smooth muscle
      specific alpha actin was expressed by stellate cells, pericentrally, with
      increasing severity and intensity in the advanced stage of fibrosis of group 3,
      less intense expression was noted in group 2, and expression was practically
      absent in group 1 and in nonpathologic controls. CD68 was the best marker for
      Kupffer cells and was expressed diffusely within the lobules in all groups. Its
      expression correlated directly with the degree of disease severity, progressing
      from stage I through stage III, but was absent in nonpathologic livers. CD34 was
      consistently expressed by endothelial cells in the periportal areas in all
      groups. The expression of collagen type 1 was intense in the bands of fibrosis or
      bridging, while type 3 expression was poor. Transforming growth factor beta1 and
      intercellular adhesion molecule 1 were not expressed in any group. CONCLUSIONS:
      In this study, stellate cell activation (SMSA) was most intense pericentrally in
      the early stages and diffusely with progression to fibrosis and maximum intensity
      in stage III. Kupffer cell activation, as determined by CD68 expression, was
      intense and diffuse, while endothelial cells expressed CD34 periportally in a
      similar manner in all stages. Fibrogenesis in human ethanol injury is due to the
      activity of stellate cells, Kupffer cells, and to a lesser extent, to endothelial
      cells.

PMID- 15504058
TI  - How the pediatric autopsy yields valuable information in a vertically integrated
      health care system.
AB  - CONTEXT: Although autopsy rates have declined significantly in recent decades,
      studies continue to validate the autopsy as an important source of clinically
      relevant information, a teaching tool, and a quality assurance measure. A recent
      review of autopsy series showed a decline in the number of serious errors likely
      to have affected clinical outcome detected at autopsy during the past 46 years,
      with a current major error rate of 8.4% to 24.4%. OBJECTIVE: Our hypothesis was
      that the pediatric autopsy would uncover a significant number of major unexpected
      findings at the high end of the spectrum predicted by a recent review. This study
      assesses the unexpected findings at a pediatric hospital whose autopsy service
      handles both in-house (tertiary care) and referral (mostly perinatal) cases for a
      vertically integrated health care system. DESIGN: Data were analyzed from an
      autopsy effectiveness report completed for all autopsies performed in 2000. The
      data from this series include concordance of premortem and postmortem diagnoses,
      with the autopsy considered the criterion standard. The autopsy effectiveness
      report also provided logistic information, such as problems with consents,
      medical records, specimen identification, and prosection. SETTING: Pediatric
      autopsies were performed by members of the Pediatric Pathology Division in a
      freestanding children's hospital in the Intermountain West of the United States
      with a large rural catchment area. This hospital is part of a large health
      maintenance organization serving the surrounding urban and rural areas. PATIENTS:
      A sample of all in-house and referral autopsies for the year 2000 was examined.
      MAIN OUTCOME MEASURE: The percentage of cases with a major or minor diagnostic
      discrepancy or unexpected pathologic finding using the autopsy as the criterion
      standard. RESULTS: The overall autopsy rate was 40% (39 hospital autopsies and 15
      forensic autopsies per 135 total deaths) and was 32% excluding forensic cases.
      Twenty-two additional referral autopsies from outside institutions were
      performed. Of 61 autopsies, 12 (20%) revealed a major diagnostic discrepancy or
      unexpected pathologic finding, 17 (28%) had a minor unexpected finding or
      additional diagnosis, 41 (67%) clarified the differential diagnosis, 46 (75%)
      confirmed or verified a major diagnosis, and 21 (34%) provided information
      regarding treatment effects. Additionally, 3 (5%) had problems with
      identification, and 12 (20%) had problems with consent, all of which were
      resolved prior to initiation of the autopsy. CONCLUSIONS: These data confirm the
      value of the pediatric autopsy in a children's hospital and a vertically
      integrated health care system. It is an important medical and quality assurance
      procedure for assessing the accuracy of diagnoses, clarifying differential
      diagnoses, yielding unexpected findings, and providing feedback regarding
      therapeutic outcomes.

PMID- 15504059
TI  - What is a picture worth? Digital imaging applications in autopsy reports.
AB  - CONTEXT: An image-enhanced report (IER) containing color digital images can serve
      as an educational tool and document important gross and microscopic findings in
      anatomic pathology. OBJECTIVE: To determine the clinical impression of IERs on an
      academic autopsy service. DESIGN: Autopsy IERs were initiated at this institution
      in December 2001. From January 2002 to July 2003, 261 hospital-service autopsies
      were performed; color images were produced for 39 (15%) of these autopsies. Of
      these IERs, 29 were distributed to 74 hospital-employed physicians. Each hospital
      physician recipient was sent a 6-question e-mail survey to evaluate his or her
      impression of image quality and added value. RESULTS: Of the 74 hospital-employed
      physicians sent an IER, 41 responded to the survey (response rate, 55%). Twenty
      one respondents recalled receiving a report with color images. Image quality was
      uniformly rated as good or excellent. Ninety-five percent thought the images
      increased their understanding of the report, and 76% thought that the images
      increased the utility of the report. All respondents stated they would (or did)
      use the images for educational purposes. Twenty-one percent of all respondents
      thought the presence of color images would increase their likelihood of
      requesting a future autopsy. CONCLUSIONS: Color digital images are perceived as a
      valuable addition to the autopsy report. Although clinicians did not consider
      color images a strong motivator to request a future autopsy, most thought that
      the images enhanced their understanding and the utility of the report. All
      respondents stated they would use the images to educate themselves, medical
      students, residents, and/or the patient's family.

PMID- 15504060
TI  - Combining human papillomavirus testing or cervicography with cytology to detect
      cervical neoplasia.
AB  - CONTEXT: Cervicography and oncogenic human papillomavirus (HPV) testing have been
      proposed for improving the accuracy of cervical cancer screening. OBJECTIVE: To
      examine whether cervicography and HPV testing can improve beyond chance the
      detection of cervical intraepithelial neoplasia (CIN) 2 or 3 in women with
      atypical cells of undetermined significance or low-grade squamous intraepithelial
      lesions on cytology. DESIGN: Cross-sectional analysis. Oncogenic HPV testing by
      Hybrid Capture II assay or cervicography combined with cytology was compared with
      the reference standard of colposcopy with directed biopsy. SETTING: Community
      family practices. PARTICIPANTS: Three hundred four women with low-grade cytologic
      abnormality. MAIN OUTCOME MEASURES: The gain in accuracy for detecting histologic
      CIN 2 or 3 or carcinoma. Because an adjunct test may improve sensitivity by
      chance alone, the sensitivity or specificity if the second test performed
      randomly was estimated. RESULTS: Cervical intraepithelial neoplasia 2 or 3 was
      found in 11.8% (36/304) of the women and invasive squamous cell carcinoma in 0.3%
      (1/304). The sensitivity of cytology for detecting CIN 2 or 3 was 73.0% and
      increased by 21.6% to 94.6% with the addition of a cervigram showing a low-grade
      lesion or higher or a positive HPV test result. These gains were reduced to 8.1%
      and 10.8% above the sensitivities expected if the additional tests performed
      randomly. The corresponding specificities decreased from 49.1% to 32.2% and
      33.0%. There was insufficient power to determine whether observed sensitivities
      were statistically significantly higher than the expected sensitivities.
      CONCLUSION: Adjunctive HPV testing or cervicography may provide similar gains in
      sensitivity, but they can appear misleadingly large if chance increases are not
      taken into account.

PMID- 15504061
TI  - Hyperhomocysteinemia measured by immunoassay: a valid measure of coronary artery
      atherosclerosis.
AB  - CONTEXT: Homocysteine is emerging as a novel marker of atherothrombosis. Its role
      as an independent risk factor for cardiovascular disease is generally accepted.
      There is scanty data correlating homocysteine levels measured by immunoassay with
      cardiovascular disease. We previously validated a fluorescence polarization
      immunoassay for measuring homocysteine, which compared favorably with high
      performance liquid chromatography. OBJECTIVE: To determine if homocysteine levels
      measured by immunoassay correlate with extent of atherosclerotic burden, as
      represented by degree of coronary artery stenosis determined by coronary
      angiography. DESIGN: Fasting plasma samples were obtained from patients
      undergoing coronary angiography (N = 165). Homocysteine levels were measured by
      immunoassay and coronary artery stenosis was determined by coronary angiography.
      RESULTS: Median coronary artery stenosis for the 3 homocysteine subgroups, less
      than 1.35, 1.35 to 6.75, and greater than 6.75 mg/L (<10, 10-15, and >15
      micromol/L), was 75%, 90%, and 99%, respectively (P = .01 for trend). Also,
      folate and vitamin B12 levels decreased with increasing homocysteine levels (P =
      .01 and .04, respectively, for trend). Spearman's correlation showed a
      significant association between homocysteine level and coronary artery stenosis
      (r = 0.20; P = .009). When men and women were examined separately, the
      correlation was significant only for women (r = 0.30; P = .01). CONCLUSION:
      Homocysteine levels, as measured by immunoassay, show a positive correlation with
      cardiovascular disease in women. Thus, this is a valid measure of atherosclerotic
      burden and, therefore, a reliable addition to the established laboratory
      repertoire for the assessment of cardiovascular disease.

PMID- 15504062
TI  - Soft tissue amyloidoma of the extremities: a case report and review of the
      literature.
AB  - The deposition of amyloid as a distinct, clinically apparent mass is uncommon,
      particularly in soft tissues. Among reported sites of soft tissue amyloidomas,
      the extremities are quite rare. Amyloid tumors can mimic malignant neoplasms both
      clinically and radiologically. We report a case of AA amyloidoma presenting in
      the deltoid region with radiological features suggesting sarcoma. Cytomorphology
      from fine-needle aspiration material, tissue histology, and appearance by
      magnetic resonance imaging are described. The literature on soft tissue
      amyloidoma is reviewed.

PMID- 15504063
TI  - Renal tumor with overlapping distal nephron morphology and karyotype.
AB  - Although most renal epithelial tumors are derived from the proximal nephron,
      approximately 10% are believed to originate in the distal nephron. This latter
      group encompasses oncocytoma, chromophobe renal cell carcinoma, and several rare
      types, including collecting duct carcinoma and renal medullary carcinoma. Despite
      progress in the classification of renal tumors, a small subset of renal
      carcinomas remains unclassified (ie, renal cell carcinoma, not otherwise
      specified). We describe a metastatic tumor consisting of cells with overlapping
      distal nephron morphologies, including foci of oncocytoma, chromophobe renal cell
      carcinoma, and collecting duct carcinoma, as well as sarcomatoid
      dedifferentiation. Special stains were inconclusive, and ultrastructural study
      demonstrated abundant mitochondria and no microvesicles. The karyotype was
      hypodiploid with 41 chromosomes and abnormalities reported in all 3 phenotypes
      present. Rearrangements of 1p and of 11q13 previously seen in divergent subsets
      of oncocytomas were concomitantly present in the current tumor. Thus, this
      malignancy has features consistent with distal nephron derivation and
      demonstrates the convergence of the varied tumor morphologies arising within this
      site. Furthermore, this case exemplifies the value of cytogenetic analysis in the
      characterization of renal cell carcinoma, not otherwise specified. In view of
      recent advances in treatment approach, especially for collecting duct carcinoma,
      further categorization of this nondescript and heterogeneous group of renal cell
      carcinomas, not otherwise specified, at least by its derivation in relationship
      to the renal nephron (distal vs proximal), may be of value in the choice of
      treatment modality.

PMID- 15504064
TI  - Primary combined squamous and small cell carcinoma of the larynx: a case report
      and review of the literature.
AB  - Primary laryngeal carcinomas comprise approximately 2% to 5% of all malignancies
      worldwide. Of these laryngeal carcinomas, approximately 99% are primary squamous
      cell carcinomas. During the past 30 years, about 160 cases of primary small cell
      carcinoma of the larynx have been reported. Combined primary squamous and small
      cell carcinoma of the larynx, the so-called composite tumor of the larynx, is
      even more rare, with only 13 published cases to date. Although the major risk
      factors for developing these composite tumors of the larynx are thought to be
      similar to other more common neoplasms of the larynx, such as squamous cell
      carcinoma, the treatment and prognosis are different. We report an additional
      case of combined small cell carcinoma of the larynx and discuss the histogenesis
      of this unusual neoplasm.

PMID- 15504065
TI  - Peliosis hepatis associated with lymphoplasmacytic lymphoma: an autopsy case
      report.
AB  - A 72-year-old man with no previous history of liver disease was admitted to our
      university hospital with severe dyspnea, edema of the lower limbs, and weight
      loss. Within a few days of hospitalization, he died due to severe bleeding in the
      upper digestive tract. At autopsy, the liver displayed typical gross features of
      peliosis hepatis. In addition, a diffuse infiltration of liver, spleen, bone
      marrow, and lymph nodes by lymphoplasmacytic lymphoma was disclosed by light
      microscopy. In the liver, the neoplastic cells partially filled the peliotic
      cavities. Peliosis hepatis is a rare liver disease characterized by multiple
      blood-filled, dilated cavities within the liver parenchyma. Association of
      lymphoplasmacytic lymphoma and peliosis hepatis has rarely been reported in the
      literature. The pathologic findings of such an unusual association and a review
      of the literature are presented.

PMID- 15504066
TI  - Diffuse giant inflammatory polyposis: a challenging clinicopathologic diagnosis.
AB  - Giant inflammatory polyposis of the colon is an uncommon manifestation of
      inflammatory bowel disease. We report a unique case of localized diffuse giant
      inflammatory polyposis in a 58-year-old white man, which was characterized by
      recurrence following initial surgical resection. The patient presented with
      symptoms of abdominal pain and passing blood per rectum. Colonoscopic examination
      revealed a near-obstructing, "fungating" mass in the sigmoid colon, which
      clinically was thought to represent colon carcinoma. Histology of several colon
      biopsies revealed marked acute inflammation with microabscess formation of the
      polyps and the adjacent mucosa. There was no evidence of dysplasia or malignancy.
      Because malignancy was strongly suspected and to relieve the obstructive
      symptoms, the patient underwent a segmental colectomy. The histologic features of
      the resected mass showed giant polyps with acute inflammation diagnostic of giant
      inflammatory polyposis. Again, there was no evidence of malignancy. Seven months
      later, following an uneventful initial postoperative recovery, the patient
      developed a recurrence of the mass with obstructive symptoms and required further
      surgical resection. The gross and histologic features of the lesion were similar
      to the previous findings. This case highlights the varied presenting symptoms and
      deceptive gross colonoscopic and radiologic features of localized diffuse giant
      inflammatory polyposis. Finally, the presence of inflammation at the resection
      margins appears to predict recurrence or persistence of the disease.

PMID- 15504067
TI  - Epithelioid hemangioendothelioma of the suprasellar area: a case report and
      review of the literature.
AB  - Intra-axial involvement of the brain by an epithelioid hemangioendothelioma is
      rare, and biological properties of the tumor are uncertain. Most of the primary
      brain manifestations are confined to the cerebral hemispheres. We report magnetic
      resonance imaging and microscopic findings of a case of suprasellar involvement
      by an epithelioid hemangioendothelioma. The tumor was treated with a subtotal
      resection only, and no progression of the disease was noted during a 6-month
      follow-up. Review of the literature suggested that most epithelioid
      hemangioendotheliomas in the brain are unifocal tumors with a rather favorable
      clinical outcome.

PMID- 15504068
TI  - Pathologic quiz case: a 49-year-old woman with an adrenal mass. Pancreatic tissue
      with nesidiodysplasia, adrenocortical adenoma, and ovarian thecal metaplasia in
      the adrenal gland.

PMID- 15504069
TI  - Pathologic quiz case: hepatosplenomegaly in an infant with hypotonia and coarse
      facial features. Gangliosidosis type 1.

PMID- 15504070
TI  - Pathologic quiz case: a 39-year-old man with diffuse pleural thickening and
      massive hemothorax. Epithelioid angiosarcoma of pleura.

PMID- 15504072
TI  - Secondary leptomeningeal sarcomatosis.

PMID- 15504071
TI  - Pathologic quiz case: a 34-year-old woman with an inguinal mass. Female adnexal
      tumor of probable wolffian origin.

PMID- 15504073
TI  - Twin pregnancy with partial hydatidiform mole and coexistent fetus.

PMID- 15504074
TI  - Myocardial and cerebral infarction due to nonbacterial thrombotic endocarditis as
      an initial presentation of pancreatic adenocarcinoma.

PMID- 15504075
TI  - In hematopathology, love is everywhere.

PMID- 15504076
TI  - Chordoid glioma: clinicopathologic profile and differential diagnosis of an
      uncommon tumor.
AB  - Chordoid glioma is an uncommon low-grade brain neoplasm arising in the third
      ventricular region, predominantly in middle-aged women. It characteristically
      shows chordoma-like histologic features and glial fibrillary acidic protein
      immunoreactivity. We present a case of chordoid glioma in a previously healthy 56
      year-old woman admitted to our hospital because of a cranial trauma subsequent to
      an incidental fall. Radiologic examinations revealed a well-demarcated, partially
      cystic, enhancing mass at the level of the lamina terminalis. The lesion was
      surgically removed. The patient remained alive and well 8 months after the
      surgery. Histologically, the tumor consisted of clusters and cords of epithelioid
      cells embedded in a mucinous matrix. Lymphoplasmacytic infiltrates and Russell
      bodies were prominent. Immunohistochemically, the tumor cells were positive for
      glial fibrillary acidic protein, neurofilaments, and neuron-specific enolase,
      suggesting a divergent neuronal and glial differentiation. The Ki-67 index was
      low. The clinicopathologic profile and the differential diagnosis of this tumor
      are discussed.

PMID- 15504077
TI  - Splenic pregnancy: a case report and review of the literature.
AB  - Primary splenic pregnancy is the least common form of extrauterine pregnancy. We
      report a case of splenic pregnancy occurring in a 29-year-old woman presenting
      with acute abdomen and hemoperitoneum. Recognition of this rare form of gestation
      is of critical importance, owing to the risk of exsanguination and death, and
      should be considered in the differential diagnosis of acute abdomen in women of
      reproductive age.

PMID- 15504078
TI  - Clear cell papulosis of the skin: a case report from Singapore.
AB  - Clear cell papulosis of the skin is a rare condition; to our knowledge only 12
      cases have been reported. Here, we report for the first time a case of clear cell
      papulosis with cytokeratin 7 expression and provide a comprehensive literature
      review. A 16-month-old girl presented with 3 hypopigmented lesions in the pubic
      region that were 3 to 9 mm in diameter; 1 lesion was papular, and the other 2
      were macular. A skin biopsy revealed acanthosis with a proliferation of clear
      cells along the basal and suprabasal layers of the epidermis occurring in small
      clusters and singly. The cells had round to oval regular nuclei with abundant to
      moderate lightly eosinophilic to clear cytoplasm and intracytoplasmic mucin.
      Immunostaining produced positive results for carcinoembryonic antigen, AE1/3,
      epithelial membrane antigen, cell adhesion molecule 5.2, and cytokeratin 7 and
      negative results for gross cystic fluid disease protein, S100, and HMB-45. Clear
      cells of clear cell papulosis are mucin-positive and S100-negative glandular
      secretory epithelial cells with histogenetic features of Toker cells of nipple
      and Paget cells. Immunohistochemical features support an eccrine secretory cell
      origin because the clear cells are consistently and strongly positive for
      carcinoembryonic antigen, positive for cell adhesion molecule 5.2, and negative
      or rarely positive for gross cystic fluid disease protein.

PMID- 15504079
TI  - Isolated gastric malakoplakia: a case report and review of the literature.
AB  - A 62-year-old African American woman presented with weight loss and dyspepsia.
      She did not have any clinical evidence of immunodeficiency. Upper
      gastrointestinal endoscopy revealed multiple small polypoid lesions in the
      gastric body and fundus that appeared larger and more erythematous than usual
      fundic gland polyps. Examination of biopsy specimens revealed an infiltrate of
      large histiocytes with eosinophilic granular cytoplasm located in the lamina
      propria and containing Michaelis-Gutmann bodies. These histologic findings were
      diagnostic of gastric malakoplakia. Gastrointestinal malakoplakia is uncommon,
      and exclusive gastric involvement is extremely rare. Because occult bacterial
      infection has been postulated as the underlying cause of malakoplakia, the
      presence of Helicobacter pylori infection was investigated using
      immunohistochemical and serologic techniques, and the presence of Yersinia
      enterocolitica or Yersinia pseudotuberculosis infection was investigated by
      polymerase chain reaction assay. There was no evidence of H pylori, Y
      enterocolitica, or Y pseudotuberculosis in these biopsy specimens, and there was
      no evidence of malakoplakia or concurrent malignancy at any other site. Follow-up
      examination 12 months later revealed no endoscopic or histologic improvement.

PMID- 15504080
TI  - Pathologic quiz case: a 70-year-old woman with postmenopausal bleeding.
      Endometrial intraepithelial carcinoma, clear cell type.

PMID- 15504081
TI  - Pathologic quiz case: giant mediastinal mass in a 69-year-old man. Thymolipoma.

PMID- 15504082
TI  - Pathologic quiz case: a right adnexal mass in a postmenopausal patient. Malignant
      mixed mullerian tumor with heterologous elements arising in the fallopian tube.

PMID- 15504083
TI  - Pathologic quiz case: a 69-year-old man with a brown-black facial papule.
      Melanocytic matricoma.

PMID- 15504084
TI  - Enhancement of riboflavin-mediated photo-oxidation of glucose 6-phosphate
      dehydrogenase by urocanic acid.
AB  - We have investigated the riboflavin (RF)-sensitized inactivation of glucose 6
      phosphate dehydrogenase (G6PD) in the presence and absence of trans-urocanic acid
      (UCA). The inactivation of the enzyme results from its direct oxidation by the
      excited triplet RF in a Type-I-photosensitized reaction whose efficiency
      increases at low oxygen concentration. The addition of histidine to the system
      produced no change in the inactivation rate, discarding the participation of
      singlet oxygen in the reaction. On the other hand, the presence of UCA results in
      its bleaching, with a significant enhancement of RF-mediated inactivation of
      G6PD. Both the consumption of UCA and G6PD are faster at low oxygen
      concentrations. UCA also produced a decrease in the sensitizer photodecomposition
      yield. These results indicate that the enhancement of the RF-mediated G6PD
      inactivation observed in the presence of UCA is not a singlet oxygen-mediated
      process. It is proposed that UCA consumption and its effect on G6PD inactivation
      are due to a complex reaction sequence initiated by a direct oxidation of UCA by
      the excited sensitizer triplet. The oxidation of the semireduced flavin gives
      rise to reactive oxygen species (ROS) responsible for the increased rate of the
      process. This is supported by the protection afforded by several additives with
      ROS removal capacity: benzoate, superoxide dismutase and catalase.

PMID- 15504085
TI  - Rhodopsin phosphorylation in rats exposed to intense light.
AB  - The damaging effects of intense light on the rat retina are known to vary
      depending on the time of day of exposure. The purpose of this study was to
      determine if rhodopsin phosphorylation patterns, a measure of the activity of the
      pigment, varied in a similar manner. After 10 min in strong light (1400 lux), all
      six threonine and serine sites in the rat rhodopsin C-terminus were
      phosphorylated, with mono- to tetraphosphorylation being substantially more
      prominent than penta- to hexaphosphorylation. The level and multiplicity of
      rhodopsin phosphorylations were reduced both with the duration of light exposure
      and the duration of subsequent darkness. Although showing vast differences in
      susceptibility to light damage, rats exposed at 5 P.M. or 1 A.M. showed similar
      rhodopsin phosphorylation levels and patterns. These data indicate that a process
      controlled by circadian rhythm other than rhodopsin phosphorylation is involved
      either in damaging or mediating the damage evoked by intense light exposure.

PMID- 15504086
TI  - Comparison of structural and chemical properties of black and red human hair
      melanosomes.
AB  - Melanosomes in black and red human hair are isolated and characterized by various
      chemical and physical techniques. Different yields of 4-amino
      hydroxyphenolanaline by HI hydrolysis (a marker for pheomelanin) and pyrrole
      2,3,5-tricarboxylic acid by KMnO(4)/H(+) oxidation (a marker for eumelanin)
      indicate that the melanosomes in black hair are eumelanosomes, whereas those in
      red hair are mainly pheomelanosomes. Atomic force microscopy reveals that
      eumelanosomes and pheomelanosomes have ellipsoidal and spherical shapes,
      respectively. Eumelanosomes maintain structural integrity upon extraction from
      the keratin matrix, whereas pheomelanosomes tend to fall apart. The black-hair
      eumelanosomes have an average of 14.6 +/- 0.5% amino acids content, which is
      attributed to the internal proteins entrapped in the melanosomes granules. The
      red-hair melanosomes contain more than 44% of amino acid content even after
      extensive proteolytic digestion. This high content of amino acids and the poorly
      reserved integrity of red-hair melanosomes suggest that some proteins are
      possibly covalently bonded with the melanin constituents in addition to those
      that are entrapped inside the melanin species. Soluene solubilization assay
      indicates the absorbance of melanin per gram of sample, adjusted for the amino
      acid content, is a factor of 2.9 greater for the black-hair melanosomes than the
      red-hair melanosomes. Metal analysis reveals significant amounts of diverse heavy
      metal ions bound to the two types of melanosomes. The amount of Cu(II) and Zn(II)
      are similar but Fe(III) content is four times higher in the red-hair melanosomes.
      (13)C solid-state nuclear magnetic resonance spectra and infrared spectra are
      presented and are shown to be powerful techniques for discerning differences in
      the amino acid contents, the 5,6-dihydroxyindole-2-carboxylic acid:5,6
      dihydroxyindole ratio, and the degree of cross-linking in the pigment. Excellent
      agreement is observed between these spectral results and the chemical degradation
      data.

PMID- 15504089
TI  - [Analyzing the evolution of a Pharmacy Department using a relative value unit
      system].
AB  - INTRODUCTION: This study proposes the use of relative value units (RVU) as a
      clinical management tool to evaluate departmental services. OBJECTIVES: To
      measure productivity from 2000 to 2002 by estimating RVU. To determine RVU cost
      in constant Euros and evaluate system efficiency during this period of time.
      METHODS: Retrospective, observational study of a pharmacy department s
      production. RVU assigned to each activity have been obtained from a standardized
      document drawn up by the Sociedad Espanola de Farmacia Hospitalaria. Cost of each
      RVU was determined based on total cost assigned to the pharmacy department and
      the total number of RVUs produced. RESULTS: Drug dispensation activities account
      for 76% of the total production, followed by elaboration activities (21%).
      CONCLUSIONS: Productivity in our department has increased 46.48% in this period
      of time, while efficiency has increased by 23.8%.

PMID- 15504090
TI  - [Economic management of institutional pharmacies of the city of Rosario. Quality
      indicators proposal].
AB  - OBJECTIVE: To compare structures, procedures and results of the pharmaceutical
      management of institutional pharmacies in the city of Rosario (Argentina), to
      define the current situation and thus recommend changes. METHOD: Descriptive
      study, using a questionnaire and quality indicators of an Accreditation Program
      of Hospital Pharmacies. Evaluated dimensions: selection, acquisition, reception,
      storage and stock control of drugs and medical devices. Data was collected for a
      one-year-period in order to obtain indicators. After tabulation, data was
      discussed in meetings with all the pharmacists that participate in this study, in
      order to evaluate the situation and propose changes for the Pharmacies, as well
      as to evaluate the Program based on usefulness of these indicators. RESULTS: The
      general results illustrate how each institution has different health policies.
      43.2% of indicators were answered, 67.6% reached standard values. CONCLUSIONS:
      This work allowed for an exhaustive analysis of the current situation. The
      pharmacists made proposals and unified criteria in order to obtain an improved
      use of the economic resources of each institution.

PMID- 15504091
TI  - [Protocols implementing in a university hospital. An assessment of various
      methods].
AB  - OBJECTIVE: To establish a method for evaluating, in a systematic and periodic
      way, the degree of compliance with the protocols currently being used in the
      hospital. MATERIALS AND METHOD: Experts from the hospital designed 6 protocols
      which were later approved by consensus by several committees and agreed by
      Medical Direction. The doctors were informed of the new protocols by means of
      info-sessions and printed materials. In order to evaluate to what extent the
      protocols were complied with, we carried out a number of longitudinal and cross
      sectional studies depending on how often the protocols are used. RESULTS: The
      study involved 2,190 patients. Cross-sectional studies. Surgical antimicrobial
      prophylaxis protocol: compliance with the application forms was 83.3% and for
      surgical interventions it was 64.3%. It should be noted that adherence improved
      with time. Sliding-scale insulin therapy: compliance improved during the
      observation period from 54 to 71.1%. Prevention of NSAID induced gastropathy:
      after 6 months a significant improvement was observed in relation to the previous
      phase. Pain treatment: of the 117 analgesics prescribed on-demand in the previous
      phase, 27.3% were administered, as well as 68.4% of a total of 95 fixed
      prescriptions. In the phases previous to setting up these protocols, adherence
      ranged from 0 to 68.4%. One year later, adhesion has improved significantly for
      all the evaluated protocols. Longitudinal studies. Community acquired pneumonia:
      adhesion was 60.8%, while non significant differences were observed according to
      severity. Transitory ischemic accident: compliance evaluation showed an adherence
      value of 81.8%. CONCLUSIONS: When the degree of compliance is high, follow-up
      studies may be spaced out in time. If not, the reasons for this low compliance
      must be identified and measures must be taken. Follow-up studies must be carried
      out more often when protocols have just been set up and less frequently as
      adherence improves.

PMID- 15504092
TI  - [Pharmaceutical procedures in patients under treatment with total parenteral
      nutrition].
AB  - OBJECTIVE: To describe and analyse pharmaceutical care activities, medication
      errors and/or drug-related problems in patients with total parenteral nutrition.
      METHODS: A prospective study was carried out over a six-month period. All
      pharmaceutical care activities for patients in treatment with total parenteral
      nutrition were registered and classified. Daily patient medical and
      pharmacotherapy chart review plus patient interviews allowed the identification
      of medication errors and/or drug-related problems associated with both total
      parenteral nutrition and other pharmacological treatments. RESULTS: During the
      study period, 49 patients received total parenteral nutrition. 415 pharmaceutical
      care activities were carried out, representing a median of 8 pharmaceutical care
      activities per patient (rank: 4-18). In 33 patients, at least one medication
      error was detected (n= 63), therefore representing 1 medication error per patient
      with total parenteral nutrition every 5 days. Most frequent errors were: wrong
      dose (n= 46, 73%), incorrect treatment duration (n= 9, 14.3%) and wrong drug (n=
      5, 7.9%). All these errors originated a potential drug-related problem which
      affected indication in 50.8% of the cases; safety in 41.3% and effectiveness in
      7.9%. CONCLUSION: Results obtained during this study show a high demand for
      pharmaceutical attention in patients with total parenteral nutrition treatment.
      Identification and classification of medication errors and drug-related problems
      help to identify system points that can be improved, thus increasing assistential
      quality.

PMID- 15504093
TI  - [Outlining passive information offered by the Drug Information Center of the
      Federal University of Bahia College of Pharmacy].
AB  - OBJECTIVE: To outline passive information offered by the Drug Information Center
      (DIC) of the Federal University of Bahia College of Pharmacy. METHODOLOGY:
      Descriptive and prospective study of requests received at the DIC from March,
      1997 to December, 2003. Results, represented as frequencies, were obtained by
      using Microsoft Excel. RESULTS: 1,267 requests were received in the study period.
      Thirty seven percent (37%) of these involved patients; 73% were done by telephone
      and 66% were answered the same way; 68% of the requests were made by pharmacists.
      About 39% of all requests were originated in hospitals and 23% in community
      pharmacies. A total of 1,459 questions were received, showing a proportion of 1.2
      questions per information request, of which: 18% were related to drug
      indication/use; 13% to adverse reactions; 17% to identification of national and
      foreign products and active substances; 8% to posology and 6% to drug
      interactions. Fifty nine percent of the requests were answered within 23 hours.

PMID- 15504094
TI  - [Cytostatic prescription errors: an analysis of causes, and proposals regarding
      their prevention].
AB  - OBJECTIVE: To collect and analyze prescription errors for parenterally
      administered cytostatic drugs, to identify causes from results obtained, and to
      suggest feasible solutions to prevent them. METHOD: In our hospital, parenterally
      administered cytotoxic drugs are prepared in the Pharmacy Department, where 100%
      of prescriptions are validated with the help of a software program. Prescription
      errors detected at validation over a 2-year period of time were recorded in a
      specific form to facilitate analysis. RESULTS: In all, 292 possible errors were
      detected and 183 were confirmed; most resulted from dosing errors, followed by
      incorrect treatment duration. Other errors detected included: dose or drug
      omitted, wrong administration route, wrong patient, and wrong medication. The
      following measures were suggested: improvement of the data processing system at
      the Pharmacy Department, implementation of an electronic prescription system,
      continuous updating of cytostatic therapy protocols, and inclusion of cytostatic
      prescription recommendations within Pharmacotherapeutic Guidelines. CONCLUSION:
      Most common errors included doses above or below the correct ones, with the
      primary cause being poor handwriting in manual prescriptions. Active recording of
      prescription errors is essential if an analysis of real causes in our setting is
      to be undertaken, as well as to making proposals and implementing definite
      solutions.

PMID- 15504095
TI  - [Managing methotrexate toxicity: a case report].
AB  - High-dose methotrexate is included in chemotherapy regimens used to treat a
      number of malignant neoplasms. Methotrexate plasma concentration is considered
      the best toxicity predictor. Monitoring methotrexate plasma concentrations is
      standard practice in the identification of at-risk patients, the titration of
      folinic acid doses, and the establishment of corrective measures. Methotrexate is
      a kidney-cleared weak acid, and renal function impairment may retard methotrexate
      clearance. A case of severe methotrexate-induced toxicity secondary to renal
      failure is reported in a patient with non-Hodgkin s lymphoma receiving
      methotrexate at a dose of 1 g/m2. Corrective measures included folinic acid
      rescue therapy, cholestyramine resin administration, hydration and urine
      alkalinization, urine pH monitoring, and extracorporeal clearance techniques.

PMID- 15504096
TI  - [Establishing an insight-gaining area in pharmacoeconomics].
AB  - INTRODUCTION: The use of economic evaluation methods is very important in health
      care, in order to select those medicines that could be funded by National Health
      Services, or that could be included in the hospital or primary health care
      formularies. The development of the Clearinghouse on Pharmacoeconomics, available
      for health care professionals, represents an important advance for the
      information-knowledge system which is basic for professionals to understand how
      important it is to incorporate efficiency into decision making. Both primary
      health care and hospitals, need to assure the quality of pharmacoeconomic
      information that must be taken into account when evaluating the use of new or in
      use drugs. OBJECTIVES: To establish a Clearinghouse on Pharmacoeconomics with the
      most important resources on this subject available in Internet from the countries
      of the European Union, United States and Canada. METHODS: Descriptive study of
      web sites of institutions and centers and other pharmacoeconomics and health
      economics resources from 24 OECD countries mainly from the European Union, United
      States and Canada. RESULTS: The Clearinghouse of Pharmacoeconomics has identified
      information from 55 centers of pharmacoeconomics and health economics, 20
      journals, 32 books, 19 data bases of medicines, 14 periodic bulletins of
      pharmacoeconomics subjects, and 16 professional associations. It also includes
      articles, two-monthly bulletins and health news which can all be found in a web
      site under the denomination of Clearinghouse on Pharmacoeconomics. The number of
      visits has been of 8,488 since June 30th of the year 2000. CONCLUSIONS: A
      Clearinghouse on Pharmacoeconomics that includes the most important resources
      from the countries in the European Union, the United States and Canada related to
      pharmacoeconomics and health economics has been established. The number of visits
      from June 2000 to May 2003 was 8,488. To establish, increase and maintain the
      number of users who visit and obtain data from the clearinghouse on
      pharmacoeconomics, the use of an alert system every fifteen days has proved
      effective.

PMID- 15504097
TI  - [The URV and the evaluation of new technologies].

PMID- 15504098
TI  - [Pemetrexed (Alimta). Laboratory: Lilly].

PMID- 15504101
TI  - Novel evolutionary lineages of the invertebrate oxytocin/vasopressin superfamily
      peptides and their receptors in the common octopus (Octopus vulgaris).
AB  - The common octopus, Octopus vulgaris, is the first invertebrate species that was
      shown to possess two oxytocin/vasopressin (OT/VP) superfamily peptides,
      octopressin (OP) and cephalotocin (CT). Previously, we cloned a GPCR (G-protein
      coupled receptor) specific to CT [CTR1 (CT receptor 1)]. In the present study, we
      have identified an additional CTR, CTR2, and a novel OP receptor, OPR. Both CTR2
      and OPR include domains and motifs typical of GPCRs, and the intron- exon
      structures are in accord with those of OT/VP receptor genes. CTR2 and OPR
      expressed in Xenopus oocytes induced calcium-mediated inward chloride current in
      a CT- and OP-specific manner respectively. Several regions and residues, which
      are requisite for binding of the vertebrate OT/VP receptor family with their
      ligands, are highly conserved in CTRs, but not in OPR. These different sequences
      between CTRs and OPR, as well as the amino acid residues of OP and CT at
      positions 2-5, were presumed to play crucial roles in the binding selectivity to
      their receptors, whereas the difference in the polarity of OT/VP family peptide
      residues at position 8 confers OT and VP with the binding specificity in
      vertebrates. CTR2 mRNA was present in various peripheral tissues, and OPR mRNA
      was detected in both the nervous system and peripheral tissues. Our findings
      suggest that the CT and OP genes, similar to the OT/VP family, evolved through
      duplication, but the ligand-receptor selectivity were established through
      different evolutionary lineages from those of their vertebrate counterparts.

PMID- 15504102
TI  - Translating basic science into patient therapy for ANCA-associated small vessel
      vasculitis.
AB  - ANCA (anti-neutrophil cytoplasm antibody)-associated small vessel vasculitis is
      an inflammatory condition associated with the production of autoantibodies to
      neutrophil cytoplasmic components. The disorder results in destruction of the
      microvasculature, infiltration of neutrophils into tissues, which is followed
      later by mononuclear cells, leading to injury and the formation of granulomatous
      lesions. Initiators for the disease are undetermined but a pro-inflammatory
      environment is required. Other influencing factors may include environmental
      triggers, genetic propensity or infectious agents. The primary cellular event in
      the condition involves the neutrophils, which are likely to be responsible for
      the majority of tissue injury. Binding of the autoantibody to neutrophils
      initiates cell activation via a complex intracellular signalling cascade,
      culminating in the release of pro-inflammatory mediators, proteolytic enzymes and
      reactive oxygen species. Adhesion of neutrophils to endothelial cells is observed
      in vitro and more investigations in this area may explain the focussing of the
      disease to certain vessels/tissues. Current treatment regimens have substantial
      toxicity. Although newer developments are an improvement there is still a
      pressing need for more targeted therapies, which could be provided by
      extrapolating information emerging from basic scientific research.

PMID- 15504103
TI  - A detailed understanding of the enhanced hypothermic productivity of interferon
      gamma by Chinese-hamster ovary cells.
AB  - Culturing CHO (Chinese-hamster ovary) cells at low temperature leads to growth
      arrest in the G0/G1 phase of the cell cycle and, in many cases, causes an
      increase in the specific productivity of recombinant protein. Controlled
      proliferation is often used to increase CHO specific productivity, and thus there
      is speculation that the enhanced productivity at low temperature is due to G0/G1
      phase growth arrest. However, we show that the positive effect of low temperature
      on recombinant protein production is due to elevated mRNA levels and not due to
      growth arrest and that a cell line can still exhibit growth-associated
      productivity at low temperatures. Using a CHO cell producing recombinant human
      IFN-gamma (interferon-gamma), we show that productivity increases as the
      percentage of cells in the S phase of the cell cycle increases, at both 32 and 37
      degrees C. The increased productivity is due to higher recombinant IFN-gamma mRNA
      levels. We also show that, for a given cell-cycle distribution, specific
      productivity increases as the temperature is lowered from 37 to 32 degrees C.
      Thus specific productivity is maximized when cells are actively growing (high
      percentage of S-phase cells) and also exposed to low temperature. These findings
      have important implications for cell-culture optimization and cell-line
      engineering, providing evidence that a CHO cell line capable of actively growing
      at low temperature would provide improved total protein production relative to
      the current growth strategies, namely 37 degrees C active growth or low
      temperature growth arrest.

PMID- 15504104
TI  - Active hypothermic growth: a novel means for increasing total interferon-gamma
      production by Chinese-hamster ovary cells.
AB  - When grown under hypothermic conditions, CHO (Chinese-hamster ovary) cells become
      growth-arrested in the G0/G1 phase of the cell cycle and also often exhibit
      increased recombinant-protein production. We have shown in the accompanying paper
      [Fox, Tan, Tan, Wong, Yap and Wang (2005) Biotechnol. Appl. Biochem. 41, 255-264]
      that the positive effect of low temperature on recombinant-protein production is
      due to elevated mRNA levels and not due to G0/G1-phase growth arrest and that a
      cell line can still show growth-associated productivity at low temperature. This
      finding led to the hypothesis that improved total production of recombinant
      protein would be achieved by stimulating cells to actively grow at low
      temperature, a culture condition previously unreported in the literature. In the
      present study we have validated this hypothesis by stimulating hypothermic (32
      degrees C) growth through the use of different growth factors. Hypothermic growth
      was stimulated in fetal-bovine-serum-supplemented adherent cultures using basic
      fibroblast growth factor or insulin. Hypothermic growth was also stimulated in
      suspension cultures normally grown in protein-free medium by using
      supplementation with fetal bovine serum. These methods resulted in up to 7.7- and
      4.9-fold increases in total recombinant-protein production compared with the 37
      and 32 degrees C control cultures respectively. This proof-of-concept study will
      motivate the creation of cell lines capable of growing at low temperatures for
      use in industrial processes.

PMID- 15504105
TI  - Transcriptomic and proteomic analysis of liver and muscle alterations caused by
      surgical stress in rats.
AB  - The metabolic response to injury includes major alterations in protein
      metabolism; however, little is known about alterations in the synthesis of
      individual proteins and their role in the stress response. Our aim was to study
      how individual proteins in liver and muscle are altered by abdominal surgery.
      Changes produced in mRNA and proteins by abdominal surgery were studied in rats
      using RAP (random arbitrary priming)-PCR, to investigate mRNA alterations, and
      standard or isotopic (with in vivo radioactive labelling of proteins) two
      dimensional electrophoresis/MS proteomic analyses, to study differential
      expression of proteins. Many of the differentially expressed proteins identified
      in blood were specifically synthesized by the liver to participate in the stress
      response. The hepatic proteins (antioxidant proteins, serine protease inhibitors,
      acute-phase proteins and transport proteins) were secreted into the bloodstream
      to produce a systemic action, indicating the central role of the liver in the
      stress response. Overexpressed proteins identified in liver were associated with
      the glycolytic processes and the folding of nascent proteins, confirming the high
      metabolic activity of the liver after surgery. The role of skeletal muscle
      protein as an amino acid donor to fuel the processes involved in the stress
      response was shown by the decrease in high-molecular-mass myofibrillar proteins.
      Combined use of the three techniques studied, differential RAP-PCR and standard
      and isotopic proteome analysis, provided complementary information on the
      differentially expressed proteins in a rat model of surgical stress.

PMID- 15504106
TI  - Persistent endothelial dysfunction is related to elevated C-reactive protein
      (CRP) levels in Type II diabetic patients after acute myocardial infarction.
AB  - The atherosclerotic process is an ongoing dynamic and progressive state arising
      from endothelial dysfunction and inflammation. Although suffering from an acute
      coronary artery disease, patients with Type II diabetes have a poor outcome
      compared with non-diabetic patients, which may only partly be explained by
      traditional risk factors. Our purpose was to compare non-traditional risk
      factors, such as endothelial function, C-reactive protein (CRP) and adiponectin,
      in Type II diabetic and non-diabetic patients following AMI (acute myocardial
      infarction). Twenty Type II diabetic patients were compared with 25 non-diabetic
      patients at baseline (1-3 days from the onset of chest pain) and at 60 days
      follow-up after an AMI. Using high-resolution ultrasound, brachial artery
      responses to FMD (flow-mediated vasodilatation; endothelium-dependent
      vasodilatation) and NTG (nitroglycerine-induced vasodilatation; endothelium
      independent vasodilatation) were measured. Plasma levels of CRP and adiponectin
      were measured by ELISA. At baseline, FMD (1.9 compared with 3.2%; P=0.22) and CRP
      levels (6.95 compared with. 5.51 mg/l; P=0.40) did not differ between Type II
      diabetic and non-diabetic patients, whereas adiponectin levels were lower in Type
      II diabetic patients (2.8 compared with 5.0 ng/ml; P<0.05). At 60 days follow-up,
      there were significant differences in FMD (1.5 compared with 4.1%; P<0.02), CRP
      (4.23 compared with 1.46 mg/ml; P<0.01) and adiponectin (3.3 compared with 5.3
      ng/ml; P<0.05) levels between Type II diabetic and non-diabetic patients. In
      contrast, NTG responses improved in both groups between baseline and follow-up
      (Type II diabetic patients, 9.7 compared with 13.2% respectively, P<0.05; non
      diabetic patients, 7.9 compared with 12.4% respectively, P<0.01). These results
      show a persistent endothelium-dependent dysfunction and inflammatory activity in
      patients with Type II diabetes, but not in non-diabetic patients, after AMI.
      These findings may, in part explain, the poor outcome in coronary artery disease
      seen in Type II diabetes.

PMID- 15504107
TI  - Monitoring the formation of dynamic G-protein-coupled receptor-protein complexes
      in living cells.
AB  - GPCRs (G-protein-coupled receptors) play an extremely important role in
      transducing extracellular signals across the cell membrane with high specificity
      and sensitivity. They are central to many of the body's endocrine and
      neurotransmitter pathways, and are consequently a major drug target. It is now
      clear that GPCRs interact with a range of proteins, including other GPCRs.
      Identifying and elucidating the function of such interactions will significantly
      enhance our understanding of cellular function, with the promise of new and
      improved pharmaceuticals. Biophysical techniques involving resonance energy
      transfer, namely FRET (fluorescence resonance energy transfer) and BRET
      (bioluminescence resonance energy transfer), now enable us to monitor the
      formation of dynamic GPCR-protein complexes in living cells, in real time. Their
      use has firmly established the concept of GPCR oligomerization, as well as
      demonstrating GPCR interactions with GPCR kinases, beta-arrestins, adenylate
      cyclase and a subunit of an inwardly rectifying K+ channel. The present review
      examines recent technological advances and experimental applications of FRET and
      BRET, discussing particularly how they have been adapted to extract an ever
      increasing amount of information about the nature, specificity, stoichiometry,
      kinetics and agonist-dependency of GPCR-protein interactions.

PMID- 15504108
TI  - Role of protein-protein interactions in the regulation of pyruvate dehydrogenase
      kinase activity.
AB  - The transacetylase component (E2) of PDC (pyruvate dehydrogenase complex) plays a
      critical role in the regulation of PDHK (pyruvate dehydrogenase kinase) activity.
      The present study was undertaken to investigate further the molecular mechanism
      by which E2 modulates the activity of PDHK. In agreement with the earlier
      results, it was found that the inner L2 (lipoyl-bearing domain 2) of E2 expressed
      with or without the C-terminal hinge region had little, if any, effect on the
      kinase activity, indicating a lack of direct allosteric effect of L2 on PDHK. In
      marked contrast, significant activation of PDHK was observed with the construct
      consisting of L2 and the E1BD (E1-binding domain) of E2 (L2-E1BD didomain)
      suggesting that co-localization and/or mutual orientation of PDHK and E1,
      facilitated by E2 binding, largely account for the activation of PDHK by the
      transacetylase component. Isothermal titration calorimetry and glutathione S
      transferase pull-down assays established that binding of adenyl nucleotides to
      the PDHK molecule facilitated the release of L2 domain. In contrast, binding of
      the L2 domain caused a significant decrease in the affinity of PDHK for ATP. The
      cross-talk in binding of adenyl nucleotides and the L2 domain to PDHK may
      indicate the existence of a highly integrated mechanism whereby the exchange of
      lipoyl-bearing domains presented to PDHK by E2 is coupled with ADP/ATP exchange.

PMID- 15504109
TI  - Kinetics of bidirectional H+ and substrate transport by the proton-dependent
      amino acid symporter PAT1.
AB  - PAT1 is a recently identified member of the PAT family of proton/amino acid co
      transporters with predominant expression in the plasma membrane of enterocytes
      and in lysosomal membranes of neurons. Previous studies in Xenopus oocytes
      expressing PAT1 established proton/substrate co-transport associated with
      positive inward currents for a variety of small neutral amino acids. Here we
      provide a detailed analysis of the transport mode of the murine PAT1 in oocytes
      using the two-electrode voltage-clamp technique to measure steady-state and pre
      steady-state currents. The GPC (giant patch clamp) technique and efflux studies
      were employed to characterize the reversed transport mode. Kinetic parameters
      [K(m) (Michaelis constant) and I(max) (maximum current)] for transport of various
      substrates revealed a dependence on membrane potential: hyperpolarization
      increases the substrate affinity and maximal transport velocity. Proton affinity
      for interaction with PAT1 is almost 100 nM, corresponding to a pH of 7.0 and is
      independent of substrate. Kinetic analysis revealed that binding of proton most
      likely occurs before substrate binding and that the proton and substrate are
      translocated in a simultaneous step. No evidence for a substrate-uncoupled proton
      shunt was observed. As shown by efflux studies and current measurements by the
      GPC technique, PAT1 allows bidirectional amino acid transport. Surprisingly, PAT1
      exhibits no pre-steady-state currents in the absence of substrate, even at low
      temperatures, and therefore PAT1 takes an exceptional position among the ion
      coupled co-transporters.

PMID- 15504111
TI  - Nanotechnology and artificial organs: today and for the future.

PMID- 15504112
TI  - Mechanical and structural properties of a novel hybrid heart valve scaffold for
      tissue engineering.
AB  - Hybrid heart valve scaffolds were fabricated from decellularized porcine aortic
      heart valve matrices and enhanced with bioresorbable polymers using different
      protocols: (i) dip coating of lyophilized decellularized matrices, and (ii)
      impregnation of wet decellularized matrices. The following polymers were
      evaluated: poly(4-hydroxybutyrate) and poly(3-hydroxybutyrate-co4
      hydroxybutyrate). Tensile tests were conducted to assess the biomechanical
      behavior of valve leaflet strips. Suture retention strength was evaluated for the
      adjacent conduit. A pulse duplicator system was used for functional testing of
      the valves under physiological systemic load conditions. The properties of the
      hybrid structures were compared with native, decellularized, and glutaraldehyde
      fixed specimens. Mechanisms of the polymer impregnation process were studied with
      IR spectroscopy, fluorescent microscopic imaging, and SEM. Altogether this study
      demonstrates the feasibility and improved biomechanical function of a novel
      hybrid heart valve scaffold for an application in tissue engineering.

PMID- 15504110
TI  - ADAM disintegrin-like domain recognition by the lymphocyte integrins alpha4beta1
      and alpha4beta7.
AB  - The ADAM (a disintegrin and metalloprotease) family of proteins possess both
      proteolytic and adhesive domains. We have established previously that the
      disintegrin domain of ADAM28, an ADAM expressed by human lymphocytes, is
      recognized by the integrin alpha4beta1. The present study characterizes the
      integrin binding properties of the disintegrin-like domains of human ADAM7,
      ADAM28 and ADAM33 with the integrins alpha4beta1, alpha4beta7 and alpha9beta1.
      Cell-adhesion assays demonstrated that, similar to ADAM28, the ADAM7 disintegrin
      domain supported alpha4beta1-dependent Jurkat cell adhesion, whereas the ADAM33
      disintegrin domain did not. The lymphocyte integrin alpha4beta7 was also found to
      recognize both disintegrin domains of ADAM7 and ADAM28, but not of ADAM33. This
      is the first demonstration that mammalian disintegrins are capable of interacting
      with alpha4beta7. All three disintegrin domains supported alpha9beta1-dependent
      cell adhesion. Recognition by both alpha4beta1 and alpha4beta7 of ADAM7 and
      ADAM28 was activation-dependent, requiring either the presence of Mn2+ or an
      activating monoclonal antibody for cell attachment. Charge-to-alanine mutagenesis
      experiments revealed that the same residues within an individual ADAM disintegrin
      domain function in recognizing multiple integrins. However, the residues within a
      specific region of each ADAM disintegrin-like domain required for integrin
      binding were distinct. These results establish that ADAM7 and ADAM28 are
      recognized by the leucocyte integrins alpha4beta1, alpha4beta7 and alpha9beta1.
      ADAM33 exclusively supported only alpha9beta1-dependent adhesion.

PMID- 15504113
TI  - Two multiarticulated hydraulic hand prostheses.
AB  - PURPOSE: Consumers want new prosthetic hand designs that have increased
      functionality, better cosmetic appearance, and lower weight. METHODS: New
      lightweight hands that fulfill these demands can be designed by integrating a
      hydraulic system with small fluidic actuators at the digit joints. RESULTS: Two
      different designs of lightweight experimental prosthetic hand are presented. The
      weight of the first hand is reduced by 50% compared to a conventional prosthetic
      hand, whereas the functionality of the second hand is increased by additional
      prehension types. Optionally, a tactile feedback system can be integrated. Due to
      multiple articulated digits and flexible materials, both hands are able to
      conform to the shape of an object held. This significantly reduces the necessary
      grip force and results in stable holding of an object. For a natural appearance,
      the hands are covered with a cosmetic silicone rubber glove.

PMID- 15504114
TI  - Effect of an experimental stenosis in the porcine descending thoracic aorta.
AB  - OBJECTIVE: To investigate the alterations of mechanical properties in pre- (A)
      and post- (B) stenotic aortic regions after an experimentally induced stenosis in
      the descending thoracic aorta. METHODS: Eight healthy, normalipemic and
      normotensive Landrace pigs were subjected to thoracotomy under sterile
      conditions. In the upper segment of the descending thoracic aorta a
      circumferential symmetric constriction 5 mm in length was imposed and stabilized;
      thus, a 15-20 mm Hg pressure gradient was established. The pressure gradient was
      verified via catheterization of the vessel with pressure tip catheters. Pre- and
      poststenotic hemodynamic disturbances were recorded by the use of a bidirectional
      Doppler flowmeter. Pressure and flow measurements were carried out before, 10 min
      after, and 90 days after the creation of the stenosis. Euthanasia was performed
      after 90 days, and the descending thoracic aorta removed. In the A and B regions
      serial sections of aorta (5 mm in length) create appropriate aortic "rings," to
      test in a uniaxial tension device, in order to determine the mechanical
      properties of the vessel. Histological analysis was performed, so as to estimate
      the content (%) of collagen and elastin fibers within the aortic wall. Eight sham
      operated pigs were used as controls. RESULTS: Reverse blood flow was recorded at
      both the A and B sites, and was maintained until euthanasia. Reverse flow in the
      poststenotic region B was greater than that in the prestenotic region. Mechanical
      analysis showed that the aortic wall in A and B regions became stiffer
      particularly at high strains (P < 0.05). Histological analysis indicated that the
      percentage of elastin fibers remained almost the same in both regions while the
      percentage of collagen fibers increased considerably, especially in the B region
      (P < 0.05). CONCLUSIONS: A nonhemodynamically significant experimental stenosis
      located at the level of the descending thoracic aorta induced reverse blood flow
      before and after the stenosis. The higher the reverse flow, the more collagen
      fibers were produced and the stiffer the aortic wall. Since hypercholesterolemia
      can be ruled out as a hardening factor in the present study, disturbed flow seems
      to be an independent factor which activates fibroblasts to overproduce collagen
      and to eventually reduce the aorta's compliance.

PMID- 15504115
TI  - Comparison of a new heparin-coated dense membrane lung with nonheparin-coated
      dense membrane lung for prolonged extracorporeal lung assist in goats.
AB  - Thrombosis and bleeding are major complications in cases of prolonged
      extracorporeal lung assist (ECLA) with an artificial-membrane lung.
      Antithrombogenic treatment of the artificial-membrane oxygenator and circuits is
      indispensable for safe ECLA. The efficacy of a new heparin-coated membrane lung
      with minimal systemic heparinization was evaluated for 7 days and compared with a
      nonheparin-coated membrane lung in goats. The animals were randomly assigned to
      either the heparin-coated membrane group (HM group, n = 5) or nonheparin-coated
      membrane group (NHM group, n = 5). Activated coagulation time (ACT) during ECLA
      was controlled to below 150 s in the HM group, and to near 200 s in the NHM
      group. All goats in the HM group were sustained on ECLA for 7 days, but two goats
      in the NHM group died on the 4th and 6th days, respectively. The mean systemic
      administration rate of heparin during ECLA was 22.4 +/- 4.4 U/kg/h in the HM
      group and 39.0 +/- 10.0 U/kg/h in the NHM group. There was a significant
      difference between the two groups (P < 0.05). The oxygen transfer rate, the
      Pco(2) difference, the perfusion resistance, and platelet counts showed no
      significant changes. There was no plasma leakage from the artificial lung.
      Although several clots were observed in the stagnant areas of the artificial
      lung, they did not lead to deterioration of the function of the artificial lung.
      The excellent antithrombogenicity, gas exchange ability, and durability of this
      new artificial lung with circuits might contribute to successful prolonged ECLA
      with minimal systemic heparinization.

PMID- 15504116
TI  - A tensor-based measure for estimating blood damage.
AB  - Implantable ventricular assist devices give hope of a permanent clinical solution
      to heart failure. These devices, both pulsatile- and continuous-flow, are
      presently used as medium-term bridge to heart transplant or recovery. While long
      term use of continuous-flow axial and centrifugal pumps is being explored, the
      excessive level of blood damage in these devices has emerged as a design
      challenge. Blood damage depends both on shear stress and exposure time, and
      device designers have relied traditionally on global space- and time-averaged
      estimates from experimental studies to make design decisions. Measuring
      distributions of shear stress levels and the blood cell's exposure to these
      conditions in complex rotary pump flow is difficult. On the other hand,
      computational fluid dynamics (CFD) is now being used as a tool for designing
      viable devices, offering more detailed information about the flow field. A tensor
      based blood damage model for CFD analysis is proposed here. The model estimates
      the time- and space-dependent strain experienced by individual blood cells and
      correlates it to blood damage data from steady shear flow experiments. The blood
      cells are modeled as deforming droplets and their deformation is tracked along
      the pathlines of a computed flow. The model predicts that blood cells in a
      rapidly fluctuating shear flow can sustain high shear stress levels for very
      short exposure time without deforming considerably. In the context of mechanical
      modeling of the implantable Gyro blood pump being developed at Baylor College of
      Medicine, this suggests that blood cells traversing regions of highly fluctuating
      shear stress rapidly may not hemolyze significantly.

PMID- 15504117
TI  - Fast three-dimensional numerical hemolysis approximation.
AB  - The in vivo implantation of a mechanical device contributes to hemodynamic
      disturbances, which are responsible for damage to the membranes of red blood
      cells that in turn can lead to their rupture (hemolysis). It is important to
      ascertain at the design stage of such mechanical devices that they are innocuous
      to blood. Because there is no in vivo hemolysis index, we concentrated our
      efforts on the in vitro hemolysis index of the American Society for Testing and
      Material (ASTM) standard. We present in this work a framework for minimizing
      medical device-induced hemolysis by the development of a numerical method for
      predicting hemolysis similar to that used in in vitro experiments. The method is
      based on a novel interpretation of the Giersiepen-Wurzinger blood damage
      correlation that replaces the computation of blood damage along the streamline by
      a volume integration of a damage function over the computational domain. We
      assess the behavior and accuracy of this methodology with 3D examples.

PMID- 15504118
TI  - Modeling centrifugal cell washers using computational fluid dynamics.
AB  - Reinfusion of shed blood during surgery could avoid the need for blood
      transfusions. Prior to reinfusion of the red blood cells, the shed blood must be
      washed in order to remove leukocytes, platelets, and other contaminants. Further,
      the hematocrit of the washed blood must be increased. The feasibility of using
      computational fluid dynamics (CFD) to guide the design of better centrifuges for
      processing shed blood is explored here. The velocity field within a centrifuge
      bowl and the rate of protein removal from the shed blood has been studied. The
      results obtained indicate that CFD could help screen preliminary centrifuge bowl
      designs, thus reducing the number of initial experimental tests required when
      developing new centrifuge bowls. Although the focus of this work is on washing
      shed blood, the methods developed here are applicable to the design of centrifuge
      bowls for other blood-processing applications.

PMID- 15504119
TI  - Development of a porcine model of type 1 diabetes by total pancreatectomy and
      establishment of a glucose tolerance evaluation method.
AB  - PURPOSE: To develop and evaluate the efficacy of diabetes-targeted cell therapies
      in humans, a reliable model in larger animals is highly desirable. This article
      reports the surgical technique of total pancreatectomy in pigs and the
      biochemical analysis of the characteristics of totally pancreatectomized pigs.
      METHODS: Surgical total pancreatectomy was conducted in 23 pigs. Blood glucose,
      insulin, biochemistries, activity index, and intravenous glucose tolerance test
      (IVGTT) were examined to assess the pathophysiological profiles of diabetic pigs.
      RESULTS: A total of 14 pigs successfully underwent total pancreatectomy without
      requiring biliary reconstruction and were analyzed in the present study. Activity
      index was decreased from day 5 on and the mean survival of totally
      pancreatectomized pigs was 7.6 +/- 2.7 days. No endogenous insulin secretion was
      confirmed in these pigs. Pigs which received total pancreatectomy demonstrated
      significantly higher levels of ketone bodies. IVGTT performed within 4 days after
      total pancreatectomy showed a spontaneous decrease in blood glucose levels
      despite an absence of endogenous insulin secretion. IVGTT on day 5 or later
      showed continued hyperglycemia in pigs with total pancreatectomy. Histological
      examination showed atrophy of hepatocytes and decreased glycogen storage in the
      liver and decreased mucus production of the small intestine. CONCLUSION: This
      article describes a porcine model of diabetes created by total pancreatectomy and
      it analyzes the pathophysiological profiles in the animals. The present study has
      suggested that IVGTT on day 5 or later after total pancreatectomy is a reliable
      method to evaluate the efficacy of cell therapies.

PMID- 15504120
TI  - Effect of temporary catheter and late referral on hospitalization and mortality
      during the first year of hemodialysis treatment.
AB  - Late referral (LR) to dialysis therapy has been associated with poor outcomes in
      people with end-stage renal disease. This had been ascribed to the frequent use
      of temporary vascular catheters (TVCs) in LR patients. The effects of LR and TVC
      on the outcomes of an incident hemodialysis population (n = 101) were
      investigated. There was a higher incidence of vascular access infection, longer
      period of hospitalization, and lower survival in TVC and LR groups, compared with
      arteriovenous fistula and early referral (ER) groups, respectively. Late referral
      patients had higher number of hospitalizations than ER patients. In univariate
      analysis, LR (hazard ratio [HR] 10.8, P = 0.02) and albumin (HR 0.23, P < 0.0001)
      were associated with mortality. Late referral and body mass index were associated
      with the increased risk of hospitalization in univariate analysis. In
      multivariate analysis, LR was the only risk factor associated with
      hospitalization (HR 3.51, P = 0.002). In conclusion, LR was associated with
      increased risk of mortality and increased risk of hospitalization independently
      of the presence of a TVC.

PMID- 15504121
TI  - Relation between vertical orientation and stability of acetabular component in
      the dysplastic hip simulated by nonlinear three-dimensional finite element
      method.
AB  - In acetabular dysplasia, more vertical orientation of the acetabular component is
      often used to minimize the superolateral bone grafting. This study was designed
      to determine the effects of vertical orientation of the cup on the stability and
      polyethylene wear of the acetabular component in uncemented total hip
      arthroplasty (THA). Three-dimensional finite element models of the hemipelvis
      with dysplastic acetabulum were developed. Metal-backed hemispherical cups were
      placed in the true acetabulum with abduction angles of 35, 45, 55, and 65
      degrees. It was found that more vertical orientation of the cup was associated
      with larger relative motion of the metal shell between the acetabulum and metal
      shell. Furthermore, tilting and torsional shear stresses in the model of the cup
      abduction angle of 65 degrees were found to be 1.7 times larger than that in the
      model with 35 degrees at the bone-metal shell interface. More vertically oriented
      cups caused larger contact stresses at the articulating surfaces of the
      polyethylene liners. The results suggest that the abduction angle of the
      acetabular component significantly influences cup loosening and polyethylene wear
      in THA.

PMID- 15504122
TI  - Prevalence of Candida dubliniensis among the stored vaginal Candida isolates in a
      Turkish hospital.
AB  - In this study, 600 stored Candida species, isolated from vaginal samples of
      immunocompetent women, and phenotypically identified as C. albicans on the basis
      of a positive germ tube test, were screened for the presence of C. dubliniensis
      by three phenotypical methods. Only one strain (0.17%) failed to grow at 45
      degrees C, and produced abundant chlamydospores on both the cornmeal-Tween 80
      agar and the Staib agar. This strain was identified as C. dubliniensis by using
      the ID-32C kit (bioMerieux Vitek) and confirmed by DNA sequencing of internal
      transcript spacer (ITS) region.

PMID- 15504123
TI  - Comparative evaluation of Sensititre YeastOne vs. the NCCLS M27A protocol and E
      test for antifungal susceptibility testing of yeasts.
AB  - A recently developed microdilution method (Sensititre) YeastOne) may represent a
      valid alternative to the National Committee for Clinical Laboratory Standards
      (NCCLS) method for routine testing. The Medical Mycology Committee of the
      Associazione Microbiologi Clinici Italiani (AMCLI) decided to evaluate its
      reproducibility and reliability compared with the NCCLS M27A protocol and the E
      test. Nineteen strains each of Candida albicans and Ca. parapsilosis, isolated
      from systemic infections, were tested against amphotericin B, flucytosine,
      ketoconazole, itraconazole, and fluconazole. All the participating laboratories
      tested the YeastOne panels, while the E-test and the NCCLS method were performed
      by two laboratories each. Interlaboratory reproducibility showed a good
      correlation (from 95% for amphotericin B to 92.5% for flucytosine). The agreement
      between NCCLS and YeastOne ranged from 95 (ketoconazole and itraconazole) to 100%
      (amphotericin B and flucytosine), whereas the agreement between E-test and
      YeastOne ranged from 72.5 (fluconazole) to 100% (amphotericin B and flucytosine).
      The Sensititre YeastOne panels appear to be an excellent alternative to both the
      E-test and the NCCLS protocol for antifungal susceptibility testing.

PMID- 15504124
TI  - In vitro susceptibility testing of amorolfine in pathogenic fungi isolated from
      dermatomycosis patients in China.
AB  - The antifungal susceptibility of isolates from Chinese dermatomycosis patients to
      amorolfine was investigated following National Committee for Clinical Laboratory
      Standards (NCCLS) protocols. In total, 383 isolates were tested, including 132
      strains from tinea pedis, 148 strains from tinea corporis/cruris, and 103 strains
      from onychomycosis. The minimum inhibitory concentration (MIC) of amorolfine
      against dermatophytes ranged from 0.01 to 0.08 microg ml(-1). The MIC(50) and
      MIC(90) of amorolfine for Trichophyton rubrum were both equal to 0.04 micro ml(
      1); for T. mentagrophytes these MICs were 0.04 microg ml(-1) and 0.08 microg ml(
      1) respectively; and for Epidermophyton floccosum they were 0.02 microg ml(-1)
      and 0.04 microg ml(-1) respectively. The MIC range of amorolfine against Candida
      parapsilosis was 0.5-16 microg ml(-1). MIC(50) and MIC(90) for C. parapsilosis
      were 0.5 and 2 microg ml(-1). MIC ranges of amorolfine against Scopulariopsis
      spp. and Acremonium spp. were 0.5-4 and 2-8 microg ml(-1), respectively. Candida
      albicans, Fusarium solani and Aspergillus flavus required relatively higher
      concentrations of amorolfine to inhibit their growth (MIC 0.125-64 microg ml(-1),
      MIC(50) and MIC(90) were 4 and 64 microg ml(-1)). The results demonstrated that
      amorolfine is the only topical agent that has such a potent antifungal activity
      and a broad spectrum against a wide range of pathogenic fungi.

PMID- 15504125
TI  - Recombinant protein and DNA vaccines derived from hsp60 Trichophyton
      mentagrophytes control the clinical course of trichophytosis in bovine species
      and guinea-pigs.
AB  - Heat shock proteins (hsp) were identified in many infectious agents as
      immunodominant antigens with a protective effect. Immunization of laboratory
      animals by selected representants of hsp60, hsp70 and hsp90 isolated from several
      pathogens induced protective host immunity and significantly reduced clinical
      manifestation of infection. The present study involves preparation of a
      recombinant protein vaccine and a DNA vaccine. Both vaccines were derived from
      the hsp60 of the dermatophyte, Trichophyton mentagrophytes. Challenge trials with
      evaluation of the protective effect of vaccination were performed on calves and
      guinea-pigs. Both vaccination procedures reduced, in statistically significant
      fashion, the clinical course of skin mycosis in calves experimentally inoculated
      with the dermatophyte, T. mentagrophytes. In experiments with guinea-pigs,
      increased protection was only seen with DNA vaccination. After DNA vaccine
      application, no paravaccination side-effects (granulomas at the injection site,
      changed total state of the animal) were observed. Only vaccination with the
      recombinant protein in calf's experiment induced specific serum antibodies. This
      observation indicates that antibodies are not associated with protection. In
      summary, DNA vaccine hsp60 is the most promising for prevention of bovine
      trichophytosis.

PMID- 15504126
TI  - Itraconazole corneofungimetry bioassay on Malassezia species.
AB  - Yeasts of the genus Malassezia are part of the normal skin biocenosis and are
      involved in a series of distinct skin disorders and specific dermatomycoses in
      man and animals. Several species are currently distinguished. Their relative in
      vitro susceptibility to antifungals appears different according to the species
      and to the nature and route of administration of the drug. Corneofungimetry is an
      ex vivo bioassay allowing to test the fungal response on human stratum corneum
      following oral intake of a given antifungal by volunteers. Two series of
      cyanoacrylate skin surface strippings (CSSS) were harvested from the volar
      forearm of 30 volunteers before and after a 2-week treatment with itraconazole
      200 mg daily. They were coated by olive oil and inoculated with suspensions of
      seven different Malassezia spp. After a 1-week culture on CSSS, the amount of
      viable yeasts was assessed using neutral red staining assisted by computerized
      image analysis. Growth of the seven species was not similar on the CSSS from
      untreated stratum corneum. The ranking order from the most proliferative to the
      least was M. restricta, M. sympodialis, M. globosa, M. furfur, M. obtusa, M.
      slooffiae and M. pachydermatis. Their growth was abated to almost the same level
      after itraconazole treatment. It is concluded that in vivo treatment with
      itraconazole is highly active against all Malassezia spp. colonizing the human
      stratum corneum.

PMID- 15504127
TI  - Clinical and mycological efficacy of single-day oral treatment with itraconazole
      (400 mg) in acute vulvovaginal candidosis.
AB  - This study aimed to investigate the effectiveness of single-day oral treatment
      with itraconazole in acute vulvovaginal candidosis (VVC). Vaginitis was
      demonstrated by both detection of yeast cells and pseudohyphae formation on
      microscopic examination of vaginal discharge and mycological culture as well as
      by the clinical signs and symptoms. Clinical and mycological examinations of the
      52 patients were performed before, 1 week (short-term) and 4 weeks (long-term)
      after single-day oral treatment with itraconazole 200 mg b.i.d. The causative
      yeast fungi were: Candida albicans (76.9%), C. glabrata (9.6%), C. kefyr (9.6%)
      and C. krusei (3.9%), respectively. In short- and long-term examinations,
      clinical cure rates were found to be 61.5% and 90.4%, and mycological cure rates
      were 63.5% and 90.4%, respectively. Itraconazole was found to be 95.0% effective
      with C. albicans and 75.0% with other Candida species. It is concluded that
      treatment of acute VVC with itraconazole is safe and effective in the long-term.

PMID- 15504128
TI  - Tinea capitis caused by Microsporum canis treated with terbinafine.
AB  - Tinea capitis is a disease found throughout the world. It frequently affects
      children and only rarely adults, usually post-menopausal women. Numerous
      dermatophytes of the genus Microsporum and Tricophyton can cause tinea capitis
      and griseofulvin is still today the treatment of choice. To study the
      effectiveness and tolerability of terbinafine treatment in tinea capitis caused
      by Microsporum canis we treated 26 patients - 22 children and four women - for a
      period of 12 weeks. Dosage adopted was 62.5 mg day(-1) in patients weighing less
      than 20 kg, 125 mg day(-1) in those weighing between 20 and 40 kg, and 250 mg
      day(-1) in patients weighing more than 40 kg. Clinical and mycological healing
      was achieved in 22 patients (84.6%), tolerability was excellent and in no cases
      were side effects or abnormal results in blood chemistry tests observed.

PMID- 15504129
TI  - Detection of Cryptococcus neoformans var. grubii in honeybee (Apis mellifera)
      colonies.
AB  - The plant flora has an important role in the ecology of Cryptococcus neoformans.
      It is estimated that the environmental spreading and contamination of human
      beings with this yeast occurs via contaminated particles of plants. Cultivation
      of canopy parts of plants in selective media is the most widely used isolation
      method of this yeast. Cryptococcus neoformans var. grubii was isolated from
      honeybee colonies in Eucalyptus forests but was not isolated from the places
      where this flora did not exist. Our results indicate that the occurrence of C.
      neoformans in honeybee colonies during the flowering season of Eucalyptus spp.
      trees can be an important bioindicator for environmental yeast presence. The
      screening of honeybee colonies is a practical and a rapid method for the
      monitoring of the C. neoformans presence in flowering plants.

PMID- 15504130
TI  - Oral candidosis and associated Candida species in HIV-infected Cambodians exposed
      to antimycotics.
AB  - Although human immundeficiency virus (HIV) infection is endemic in Southeast
      Asia, data on oral mycotic flora in this disease in Asians are sparse. The aim of
      this study was to determine the prevalence of Candida species in HIV-infected
      Cambodians with oral candidosis, unexposed (group 1) and exposed to antimycotics
      (group 2) and a healthy population (group 3). In 161 HIV patients with oral
      candidosis (group 1: 121 pts; group 2: 40 pts) and in 81 controls (group 3) swab
      samples of tongue and palate were obtained. Oral candidosis was detected in 100
      and 70% of groups 1 and 2 respectively. Candida spp. were isolated from 91 and
      100% of groups 1 and 2, respectively, and from 79% of controls. Candida albicans
      was the most common, with non-albicans species such as C. tropicalis and C.
      krusei being notable. Our data indicate that variants of oral candidal infections
      in HIV disease are similar to those seen in the pre-HAART era. The particularly
      high rate of C. krusei isolation in all groups is noteworthy.

PMID- 15504131
TI  - Disseminated Scedosporium apiospermum infection in a previously healthy woman
      with HELLP syndrome.
AB  - A previously healthy 33-year-old female died of disseminated infection with
      Scedosporium apiospermum in association with Hemolysis, Elevated Liver enzymes,
      and Low Platelets (HELLP) syndrome following the delivery of twins. Her
      postpartum course was complicated by multisystem organ failure managed with
      extracorporeal membrane oxygenation (ECMO). She also developed bowel and left
      lower extremity ischemia requiring surgical resection. Blood cultures yielded S.
      apiospermum, and histologic findings revealed in vivo adventitious sporulation,
      an unusual occurrence with this pathogen. Autopsy showed extensive fungal
      infection of brain, lungs, thyroid, heart, and kidneys.

PMID- 15504132
TI  - Bizarre annular lesion emerging as tinea incognito.
AB  - Tinea incognito has first been described in 1968. The term describes a tinea
      infection whose clinical morphology has been modified by the application of
      topical corticosteroids. The clinical manifestation can masquerade a number of
      other dermatoses and leads to misdiagnosis of annular eruptions. We describe a
      patient who showed a bizarre appearance of annular, inflammatory skin lesions at
      the umbilical region. Mycological culture yielded Microsporum canis.

PMID- 15504133
TI  - Lethal otogenic Candida meningitis.
AB  - History revealed a chronic obstructive pulmonary condition which had been treated
      with prednisolone for a long time. There was a raised temperature with further
      signs of an acute inflammatory underlying disease and internal hydrocephalus.
      After performing trepanation, the symptoms of raised intercerebral pressure
      ceased. Candida albicans could be detected microbiologically in the cerebrospinal
      fluid. There was no pneumonia at the time of admission. Despite instituting
      immediate intensive care with administration of antibiotics and antimycotics, the
      patient died 11 days after inpatient admission. Autopsy revealed a C. albicans
      mycosis originating from the right middle ear with extensive suppurative
      meningitis, which was the immediate cause of death. Confluent bronchopneumonia
      had developed in both lower lung lobes at the time of death, but did not show any
      signs of mycosis and had contributed indirectly to the death of the patient.

PMID- 15504135
TI  - Predictors of outcome in renal vasculitis.

PMID- 15504136
TI  - Leptin kinetics during peritoneal dialysis in acutely uraemic rats.
AB  - BACKGROUND: Leptin has been shown to function as an inhibitor of appetite and
      energy expenditure accelerator. However, it was recently reported that leptin has
      other important functions as a fibrogenetic factor and a novel, independent risk
      factor for coronary heart disease. The present study aimed to assess the blood
      concentration of leptin in acute uraemic rats by using various peritoneal
      dialysis (PD) solutions. METHODS: To induce acute renal failure, the bilateral
      renal arteries were ligated via a mid-abdominal incision 1 h before starting PD.
      Rats were divided into four groups: 13.6 g/L glucose-containing dialysate (group
      L); 38.6 g/L glucose-containing dialysate (group H); 13.6 g/L glucose and 25 g/L
      mannitol-containing dialysate with equal osmotic pressure to the dialysate of
      group H (group M); and renal failure without PD (group F). The concentrations of
      glucose, urea nitrogen (UN), leptin and insulin were measured at 0, 2 and 4 h
      after starting PD. RESULTS: We observed significant blood UN suppression in all
      dialysed groups. Blood glucose was significantly higher in rats treated with the
      high glucose solution than in those treated with the low glucose solution.
      Insulin and leptin significantly increased in the high glucose solution group.
      There was a strong correlation between the blood glucose and insulin levels. We
      also found a strong correlation between the percentage changes in blood glucose
      and leptin. The relationship between the percentage changes in insulin and leptin
      were weak but significant. CONCLUSION: The high glucose PD solution resulted in
      increased circulating levels of leptin, glucose, and insulin, suggesting that
      these changes are linked with PD performed with glucose-based dialysis fluid.

PMID- 15504137
TI  - Simultaneous multiple tendon ruptures complicating a seizure in a haemodialysis
      patient.
AB  - Non-traumatic rupture of large tendons is identified as a contributor to
      morbidity in patients who receive haemodialysis. The injury is likely to become
      more common as the duration of survival on dialysis extends. A number of
      predisposing factors leading to tendon injury have been identified in the
      literature, including secondary hyperparathyroidism, beta(2)-microglobulin
      associated amyloidosis, corticosteroid treatment and fluoroquinolone antibiotic
      use. This is a case report of a 31-year-old male who presented with simultaneous
      large tendon ruptures following epileptiform seizures. These occurred after 10
      years of treatment for end-stage renal failure, including haemodialysis, with
      progressive secondary hyperparathyroidism. A review of the literature confirms
      progressive hyperparathyroidism as an important risk factor for large tendon
      rupture in patients on haemodialysis.

PMID- 15504138
TI  - Effects of calcium antagonists in hypertensive patients with renal dysfunction: a
      prospective, randomized, parallel trial comparing benidipine and nifedipine.
AB  - BACKGROUND: Although calcium antagonists, derived from dihydropyridine (DHP), are
      important agents in achieving control in a majority of patients with high blood
      pressure and renal disease, there are no comparative data regarding their
      inhibitory effects on the progression of renal dysfunction in Japan. METHODS:
      Benidipine and nifedipine retard both calcium antagonists derived from DHP and
      were compared in terms of their inhibitory effect on the progression of renal
      dysfunction in hypertensive patients. The primary end-points were defined as 1.5
      times the serum creatinine value at baseline, progression to end-stage renal
      failure (ESRF) necessitating dialysis or renal transplantation, and death.
      RESULTS: During the study period, a significant decline in blood pressure was
      observed in the two groups, with no significant difference between them. The
      worsening of nephropathy was significantly inhibited in the benidipine group as
      compared with the nifedipine retard group (log-rank test: P = 0.014, Wilcoxon's
      test: P = 0.022). Among the subjects who reached a primary end-point, one (33%)
      in the benidipine group and five (50%) in the nifedipine retard group were placed
      on haemodialysis within 1 year. CONCLUSION: It appears that benidipine inhibits
      the progression of hypertensive renal diseases more effectively than nifedipine
      retard.

PMID- 15504139
TI  - Impaired nitric oxide- and endothelium-derived hyperpolarizing factor-dependent
      dilation of renal afferent arteriole in Dahl salt-sensitive rats.
AB  - BACKGROUND AND AIMS: We previously demonstrated that acetylcholine elicited
      nitric oxide-dependent sustained and endothelium-derived hyperpolarizing factor
      (EDHF)-dependent transient dilation of afferent arterioles. The present study
      examined whether free radicals interacted with nitric oxide-dependent and EDHF
      dependent vasodilator mechanisms in renal microvessels of salt-sensitive
      hypertension, using the isolated perfused hydronephrotic kidney. METHODS AND
      RESULTS: Following the pretreatment with indomethacin (100 micromol/L) with or
      without nitro- l-arginine methylester (100 micromol/L), the effect of
      acetylcholine on noradrenaline (0.3 micromol/L)-induced constriction was
      evaluated in kidneys from Dahl salt-sensitive and salt-resistant rats. Although
      acetylcholine (0.01-10 micromol/L) caused dose-dependent and sustained
      vasodilation of afferent arterioles, attenuated dilation was observed in Dahl
      salt-sensitive rats, compared with that in salt-resistant rats (58 +/- 4 vs 101
      +/- 11% reversal at 10 micromol/L acetylcholine). In the presence of nitro- l
      arginine methylester, acetylcholine elicited only transient dilation, with
      vasodilator response blunted in Dahl salt-sensitive rats (64 +/- 4 vs 100 +/- 9%
      reversal at 10 micromol/L acetylcholine). Furthermore, chronic (8-10 weeks)
      treatment with tempol caused partial restoration of acetylcholine (10 micromol/L)
      induced sustained arteriolar dilation (71 +/- 3% reversal), but complete reversal
      of transient dilation (92 +/- 4% reversal). Finally, acute treatment with tempol
      not only improved the sustained component of the acetylcholine-induced dilation
      but also restored the impaired responsiveness of transient dilation in Dahl salt
      sensitive rats. CONCLUSION: Both sustained (nitric oxide-mediated) and transient
      (EDHF-mediated) components of acetylcholine-induced afferent arteriolar dilation
      were attenuated in Dahl salt-sensitive rats, which was attributed, in part, to
      enhanced free radical activity. A reversal of the sustained and transient
      vasodilation by the acute tempol treatment suggests possible interaction between
      free radicals and EDHF as well as increased bioavailability of nitric oxide.

PMID- 15504140
TI  - Macrophage accumulation and renal fibrosis are independent of macrophage
      migration inhibitory factor in mouse obstructive nephropathy.
AB  - BACKGROUND AND AIM: The progression of renal injury, initiated by either an
      immune or non-immune insult, is closely associated with the accumulation of
      leucocytes and fibroblasts in the damaged kidney. Macrophage migration inhibitory
      factor (MIF) regulates leucocyte activation and fibroblast proliferation in
      vitro. Studies have identified a pathological role for MIF in immune-initiated
      renal injury in the rat. In this study, we examined the role of MIF in
      obstructive nephropathy, where renal injury is initiated by a non-immune insult.
      METHODS AND RESULTS: Unilateral ureteric ligation was performed on MIF wildtype
      (+/+) and MIF deficient (-/-) mice. Groups of five mice were killed at days 0, 1,
      5 or 10 after obstruction, and kidneys were examined via immunohistochemistry and
      northern blotting. In MIF +/+ mice, expression of the MIF protein increased in
      obstructed kidneys compared to normal control kidneys. Interstitial macrophage
      and T cell accumulation was significantly increased in obstructed kidneys at day
      5 and 10, but was unaffected by MIF deficiency. Osteopontin and macrophage colony
      stimulating factor (M-CSF) mRNA expression in obstructed kidneys were equally
      increased in both genotypes, indicating that expression of these chemokines is
      not influenced by MIF. No difference was detected in the development of renal
      fibrosis in obstructed MIF +/+ and MIF -/- kidneys, as assessed by myofibroblast
      accumulation and proliferation and expression of profibrotic molecules
      (transforming growth factor-beta 1(TGF-beta1) and collagen). CONCLUSION: These
      results demonstrate that MIF expression is increased in obstructive nephropathy
      without affecting kidney leucocyte accumulation or the development of renal
      fibrosis. This suggests that the progression of renal injury in obstructive
      nephropathy is independent of MIF.

PMID- 15504141
TI  - Angiotensin II facilitates autoregulation in the perfused mouse kidney: An
      optimized in vitro model for assessment of renal vascular and tubular function.
AB  - BACKGROUND AND AIMS: We have optimized the isolated perfused mouse kidney (IPMK)
      model for studying renal vascular and tubular function in vitro using 24-28 g
      C57BL6J mice; the wild type controls for many transgenic mice. METHODS AND
      RESULTS: Buffer composition was optimized for bovine serum albumin concentration
      (BSA). The effect of adding erythrocytes on renal function and morphology was
      assessed. Autoregulation was investigated during stepped increases in perfusion
      pressure. Perfusion for 60 min at 90-110 mmHg with Krebs bicarbonate buffer
      containing 5.5% BSA, and amino acids produced functional parameters within the in
      vivo range. Erythrocytes increased renal vascular resistance (3.8 +/- 0.2 vs 2.4
      +/- 0.1 mL/min.mmHg, P < 0.05), enhanced sodium reabsorption (FE(Na) = 0.3 +/-
      0.08 vs 1.5 +/- 0.7%, P < 0.05), produced equivalent glomerular filtration rates
      (GFR; 364 +/- 38 vs 400 +/- 9 microL/min per gkw) and reduced distal tubular cell
      injury in the inner stripe (5.8 +/- 1.7 vs 23.7 +/- 3.1%, P < 0.001) compared to
      cell free perfusion. The IPMK was responsive to vasoconstrictor (angiotensin II,
      EC50 100 pM) and vasodilator (methacholine, EC50 75 nM) mediators and showed
      partial autoregulation of perfusate flow under control conditions over 65-85
      mmHg; autoregulatory index (ARI) of 0.66 +/- 0.11. Angiotensin II (100 pM)
      extended this range (to 65-120 mmHg) and enhanced efficiency (ARI 0.21 +/- 0.02,
      P < 0.05). Angiotensin II facilitation was antagonized by methacholine (ARI 0.76
      +/- 0.08) and papaverine (ARI 0.91 +/- 0.13). CONCLUSION: The IPMK model is
      useful for studying renal physiology and pathophysiology without systemic
      neurohormonal influences.

PMID- 15504142
TI  - Antineutrophil cytoplasmic antibody-associated glomerulonephritis in Taiwanese.
AB  - AIMS: This retrospective study defined the clinical features and outcome of
      antineutrophil cytoplasmic antibody-associated glomerulonephritis in 18
      seropositive Taiwanese patients (11 male, seven female; median age 64 years;
      range 21-82 years) with biopsy-proven pauci-immune necrotizing crescentic
      glomerulonephritis. RESULTS: Fourteen patients had a diagnosis of systemic
      vasculitis including 10 with microscopic polyangiitis and four with Wegener's
      granulomatosis; the remaining four had only glomerulonephritis. At onset, 100% of
      the systemic vasculitis patients had pulmonary lesions with or without
      haemoptysis, and 29% presented with seizure in the absence of a defined brain
      lesion. Median serum creatinine concentration was 362.4 micromol/L (range 61.9
      857.5 micromol/L) and dialysis therapy was needed in six patients. During follow
      up (median 16.5 months; range 2-72 months), treatment included cyclophosphamide
      and corticosteroids (n = 8) or corticosteroids alone (n = 7). In some patients,
      treatment improved (n = 4) or stabilized (n = 4) renal function. But chronic
      dialysis was needed in the other 10 patients. Follow-up death occurred because of
      sepsis (n = 3) and haemorrhage (n = 2). Patient survival rates were 78% (1 year)
      and 72% (5 years). Renal survival rates were 56 and 39% at 1 and 5 years,
      respectively. Of the candidate clinical and pathological parameters, chronic
      glomerular lesions in renal biopsy were the only determinant of poor renal
      outcome (P = 0.006). CONCLUSION: Antineutrophil cytoplasmic antibody-associated
      glomerulonephritis should be considered in nephritic patients with extrarenal
      manifestations, especially pulmonary infiltrate, unexplained seizure, and fever
      of an unknown origin in Taiwanese patients. Renal biopsy should be performed
      before initiating immunosuppressive therapy because the most common cause of
      mortality was sepsis.

PMID- 15504143
TI  - Polymorphism of renin-angiotensin system genes in IgA nephropathy.
AB  - BACKGROUND AND AIMS: Individuals are prone to disease because of certain disease
      susceptible genes. The angiotensin I-converting enzyme (ACE) gene
      insertion/deletion (I/D), the angiotensinogen (AGT) gene, M235T, and the
      angiotensin II type 1 receptor (ATR) gene, A1166C, polymorphisms have been
      associated with IgA nephropathy (IgAN) and its progression. Several studies on
      Caucasians and Japanese patients have reported contradictory results. We
      determined these polymorphisms in 118 Chinese patients with IgAN and 94 healthy
      Chinese subjects to assess their clinical impact. METHODS: Genotyping was
      performed with DNA isolated from peripheral leucocytes, polymerase chain reaction
      amplification of the polymorphic sequence, restriction enzymes digestion, and
      separation and identification of DNA fragments. Clinical data at renal biopsy and
      final status on renal function were determined from patients' records. RESULTS:
      Comparing all IgAN patients with controls, AGT and ATR genotype distributions
      were similar, whereas there was a significant increase in the ACE DD genotype (P
      < 0.05). When comparing patients with end-stage renal failure (IgAN-ESRF) and
      those without (IgAN-nonESRF), there was no difference among the three gene
      polymorphisms. In contrast, there were significant differences in higher male
      prevalence (P < 0.05), increased serum creatinine at presentation (P < 0.05),
      more sclerosis (P < 0.01) and higher tubulointerstitial lesion score (P < 0.001)
      in the IgAN-ESRF group. CONCLUSION: Among the ACE, AGT and ATR gene
      polymorphisms, only the DD genotype may predispose the individual to IgAN in the
      Chinese population. None are significant for prognosticating ESRF.

PMID- 15504144
TI  - A novel NPHS2 gene mutation in Turkish children with familial steroid-resistant
      nephrotic syndrome.
AB  - We report in this paper two siblings aged 8 and 17 months who were clinically
      diagnosed with familial steroid-resistant nephrotic syndrome (SRNS). By mutation
      screening of the NPHS2 gene, a homozygous missense mutation, P118L, was detected
      in both children. This study is the first systematic investigation of NPHS2 gene
      mutations in Turkish children with familial SRNS. If this mutation is a hot spot
      of mutation in the Turkish population, screening this novel mutation in Turkish
      children with SRNS may be of great clinical use to prevent unnecessary treatment
      modalities, provide accurate genetic counselling and predict the prognosis of the
      disease.

PMID- 15504145
TI  - Medicinal herbal extracts -- renal friend or foe? Part one: the toxicities of
      medicinal herbs.
AB  - In recent years, an increasing percentage of people from industrialized countries
      have been using complementary and alternative medicines (CAM). This, combined
      with numerous warnings regarding the potential toxicity of these therapies,
      suggests the need for practitioners to keep abreast of the reported incidence of
      renal toxicity caused by the ingestion of medicinal herbs. The goal of the
      present two-part series, on the toxic or beneficial effects of medicinal herbs on
      renal health, is to provide practitioners with a summary of the most recent
      information as well as the means by which evidence for benefit or toxicity has
      been found. In this first article, we explore in vivo evidence of toxicity.
      Included are nephrotoxicity from aristolochic acid and other components within
      herbs, herb--drug interactions resulting in adverse renal effects, and renal
      toxicity from contaminants within the extracts. The review aims to provide a
      guide to encourage future toxicity studies and rigorous clinical trials.

PMID- 15504146
TI  - Low protein diet causes a decrease in serum concentrations of leptin and tumour
      necrosis factor-alpha in patients with conservatively treated chronic renal
      failure.
AB  - BACKGROUND: Chronic renal failure (CRF) provokes derangement in various hormonal
      regulations of food intake and energy expenditure. In the present study, we have
      examined the effect of a low protein, low phosphorus diet on circulating levels
      of leptin, tumour necrosis factor (TNF)-alpha, and insulin in patients with CRF.
      METHODS: Seventeen male, non-diabetic subjects with conservatively treated CRF
      (estimated creatinine clearance 39.5 +/- 11.1 mL/min), and proteinuria below 2
      g/day were prospectively studied. Measurements of hormonal, metabolic and
      anthropometric parameters were performed before and after 16 weeks of dietary
      treatment (protein 0.6 g/kg of ideal body mass, 30% of calories derived from fat,
      62% of calories derived from carbohydrates and 10 mg/kg of phosphorus). Actual
      dietary intake in patients was measured by using 3-day food records and was
      supervised by the dietician. RESULTS: Body mass index and body fat mass remained
      unchanged during the 4 months of dietary treatment. Urea, leptin, and TNF-alpha
      serum concentrations decreased significantly. CONCLUSIONS: A low protein, low
      phosphorus diet reduces TNF-alpha and leptin levels in plasma. The effect on
      leptin appears not to be mediated by an insulin-dependent mechanism.

PMID- 15504147
TI  - Long-term recombinant human growth hormone use in Australian children with renal
      disease.
AB  - BACKGROUND: Recombinant human growth hormone (rhGH) has been used for 15 years to
      treat Australian children with short stature caused by chronic kidney disease.
      The Australia-wide growth hormone database, OZGROW, has prospectively collected
      data for all patients treated with rhGH. The impact of rhGH therapy on linear
      growth in patients with chronic renal failure (CRF) was assessed by
      retrospectively analysing this data. METHODS: Growth data prior to and during
      treatment, bone age, and pubertal data were recorded from the database.
      Questionnaire data provided further information on underlying renal disease,
      medication use, bone disease, and final height. Patients were classified
      according to treatment modality; conservative management of CRF, haemodialysis or
      peritoneal dialysis, and transplant. RESULTS: Data on 183 patients were analysed.
      The duration of rhGH therapy ranged from 1.2 to 10.5 years (mean 5.3 years). The
      height standard deviation score (Ht SDS) in each patient group at the start and
      end of rhGH treatment were as follows: Predialysis: -2.6 to -2.1; dialysis: -2.7
      to -2.3; transplant: -3.1 to -2.8 (P = 0.0001). Thirty-nine patients achieved
      final adult height, with mean Ht SDS before rhGH therapy being -2.65, and at
      final height it was 2.3. The mean final height for the males was 161.8 cm and for
      the females, it was 149.5 cm. CONCLUSION: The effect of treatment with rhGH was
      less dramatic than reported in the literature. However, the positive benefit of
      rhGH therapy was apparent both in the short and long-term. Therapy with rhGH
      maintained a steady Ht SDS with time; without rhGH, it would be anticipated that
      many children would show a steady decline in Ht SDS. The maximum benefit was seen
      in preterminal renal failure, and early therapy (before dialysis or
      transplantation) is recommended before an irrecoverable loss of height potential
      occurs.

PMID- 15504148
TI  - Chronic subdural haematoma and autosomal polycystic kidney disease: report of two
      new cases.
AB  - Chronic subdural haematoma (SDH) was recently described in some patients who were
      suffering from autosomic dominant polycystic kidney disease (ADPKD). It results
      in various neurological symptoms mimicking those related to intracranial
      aneurysms, which are relatively frequent in such patients. The authors report two
      cases of chronic SDH observed in two patients known to have advanced renal
      failure attributed to ADPKD. Medical imaging failed to reveal features of
      associated intracranial abnormalities such as aneurysms or arachnoid cysts.
      Surgical drainage resulted in a good recovery without relapse during a long
      period of follow up that exceeded 10 years in the first case.

PMID- 15504149
TI  - Abstracts of the 7th Asian Congress of Urology. October 31-November 4, 2004. Hong
      Kong.

PMID- 15504150
TI  - Genetically engineered animals in drug discovery and development: a maturing
      resource for toxicologic research.
AB  - Genetically engineered mice that either over-express a foreign gene (transgenic)
      or in which the activity of a specific gene has been removed ("knock-out") or
      replaced ("knock-in") will be used increasingly to investigate molecular
      mechanisms of disease, to evaluate innovative therapeutic targets, and to screen
      novel agents for efficacy and/or toxicity. Recent innovations of relevance to
      toxicologic researchers include the construction of genetically engineered mice
      with (1) multiple engineered genes, (2) mutations that can be induced at specific
      sites and times throughout life, and (3) the substitution of human genes for
      their mouse counterparts ("humanized" mice) to allow in vivo investigation of
      xenobiotic toxicity. Contemporary applications of genetically engineered mice in
      toxicology include basic mechanistic research exploiting newly engineered mouse
      lines as well as applied screening for genotoxicity and carcinogenicity using
      commercially available animals. Many caveats must be considered when interpreting
      genetically engineered mice-derived toxicity data, the chief of which will be the
      extent to which the model's phenotype has been fully characterized, the type and
      incidence of background lesions for the given mouse strain and engineered gene,
      and the possibility of misinterpreting the presence or absence of a phenotype due
      to compensatory physiologic processes that mask the outcome produced by the
      engineering event. Toxicity data acquired using genetically engineered mice
      currently supplements and in time likely will supplant those gathered using the
      present "gold standard" bioassays, as genetically engineered mice typically
      develop more lesions after a shorter latency period than do age- and strain
      matched, wild-type mice.

PMID- 15504151
TI  - The effect of tamoxifen and fluoride on bone mineral density, biomechanical
      properties and blood lipids in ovariectomized rats.
AB  - The most important aspect of therapy with fluoride and tamoxifen concerns its
      influence on bone tissue and lipid metabolism. The aim of the study was to
      evaluate the effect of tamoxifen and natrium fluoride (NaF) on bone metabolism,
      biochemical properties and blood lipids levels in ovariectomized rats. The study
      was performed in Wistar rats divided into 5 subgroups: ovariectomized controls,
      rats treated with NaF 20 mg/kg/24 hr, rats treated with NaF 20 mg/kg/24
      hr+tamoxifen 2 mg/kg/24 hr, rats treated with NaF 20 mg/kg/24 hr plus tamoxifen 4
      mg/kg/24 hr, and sham-operated controls. In ovariectomized rats the increase of
      total cholesterol, low-density lipoproteins cholesterol (LDL-cholesterol) as well
      as the decrease of bone mineral content, bone mineral density and biomechanical
      properties was observed. The therapy with NaF increased the level of total
      cholesterol, LDL-cholesterol, triglycerides, bone mineral density, bone mineral
      content. In this group the decrease of bone strength and stiffness was observed.
      The administration of tamoxifen reduced the changes in plasma lipid levels, but
      did not improve the biomechanical properties of bone tissue.

PMID- 15504152
TI  - Metabolic effects of propofol in the isolated perfused rat liver.
AB  - Inhibitory effects of the intravenous anaesthetic propofol on mitochondrial
      energy metabolism have been reported by several authors. Impairment of energy
      metabolism is usually coupled to reduction in ATP production, which in turn is
      expected to lead to several alterations in cell metabolism such as stimulation of
      glycolysis and inhibition of gluconeogenesis. The present work aimed at finding
      an answer to the question of how propofol affects energy metabolism-linked
      parameters in the isolated perfused rat liver. In the fed state, propofol
      increased glycogenolysis (glucose release), glycolysis (lactate and pyruvate
      production) and oxygen uptake in the range between 10 and 500 microM. In the
      liver of fasted rats, propofol up to 100 microM increased oxygen uptake but
      decreased gluconeogenesis from three different substrates: lactate, alanine and
      glycerol. When lactate was the substrate 50% inhibition occurred at a propofol
      concentration of 50 microM. Propofol (100 microM) decreased the ATP content of
      the liver (-33.3%), increased the AMP content (+25%) and decreased the ATP/ADP
      and ATP/AMP ratios (49 and 45%, respectively). Most effects of propofol are
      probably due to impairment of oxidative phosphorylation. Particularly, the
      combined differential action on oxygen uptake (stimulation) and gluconeogenesis
      (inhibition) is strongly suggestive of an uncoupling action also under the
      conditions of the intact cell. This effect, in turn, is consistent with the
      reported high affinity of the cellular hepatic structure, especially membranes,
      for propofol.

PMID- 15504153
TI  - The presynaptic activity of bothropstoxin-I, a myotoxin from Bothrops jararacussu
      snake venom.
AB  - Bothropstoxin-I from Bothrops jararacussu snake venom is a lysine-49
      phospholipase A(2) with myotoxic and neurotoxic activities. In this study, we
      used mouse phrenic nerve-diaphragm preparations in the absence and presence of
      manganese (Mn(2+)), a presynaptic blocker, to investigate a possible presynaptic
      action of bothropstoxin-I. At concentrations of 0.9 mM and 1.8 mM, Mn(2+)
      produced 50% neuromuscular blockade in less than 4 min., which was spontaneously
      reversible at the lower concentration. Bothropstoxin-I (1.4 microM) irreversibly
      inhibited neuromuscular blockade by 50% in 31+/-4 min. (mean+/-S.E.M., n = 9).
      Pretreating preparations with 0.9 mM Mn(2+) prevented the blockade by
      bothropstoxin-I. When added after bothropstoxin-I, Mn(2+) produced its
      characteristic blockade and, after washing, the twitch tension returned to pre
      Mn(2+) levels, indicating that bothropstoxin-I caused irreversible damage before
      the addition of Mn(2+). Electrophysiological measurements showed that a
      concentration of bothropstoxin-I (0.35 microM), which did not produce
      neuromuscular blockade, caused the appearance of giant miniature end-plate
      potentials with no change in the membrane resting potential but increased the
      quantal content. Preparations preincubated with Mn(2+) (0.9 mM, 30 min.) were
      protected against the depolarizing action of bothropstoxin-I (0.7 microM). These
      results show that, in addition to its well-known myotoxic effect, bothropstoxin-I
      also has a presynaptic action.

PMID- 15504154
TI  - Cholecystokinin-8-induced hypoplasia of the rat pancreas: influence of nitric
      oxide on cell proliferation and programmed cell death.
AB  - The background of cholecystokinin-8 (CCK-8)-induced hypoplasia in the pancreas is
      not known. In order to increase our understanding we studied the roles of nitric
      oxide and NF-kappaB in rats. CCK-8 was injected for 4 days, in a mode known to
      cause hypoplasia, and the nitric oxide formation was either decreased by means of
      N(omega)-nitro-L-arginine (L-NNA) or increased by S-nitroso-N-acetylpencillamine
      (SNAP). The activation of NF-kappaB was quantified by ELISA detection, apoptosis
      with caspase-3 and histone-associated DNA-fragmentation and mitotic activity in
      the acinar, centroacinar and ductal cells were visualized by the incorporation of
      [(3)H]-thymidine. Pancreatic histology and weight as well as protein- and DNA
      contents were also studied. Intermittent CCK injections reduced pancreatic
      weight, protein and DNA contents and increased apoptosis, acinar cell
      proliferation and nuclear factor kappaB (NF-kappaB) activation. It also caused
      vacuolisation of acinar cells. The inhibition of endogenous nitric oxide
      formation by L-NNA further increased apoptosis and NF-kappaB activation but
      blocked the increased proliferation and vacuolisation of acinar cells. The DNA
      content was not further reduced. SNAP given together with CCK-8 increased
      apoptosis and other pathways of cell death, raised proliferation of acinar cells
      and strongly reduced the DNA content in the pancreas. Histological examination
      showed no inflammation in any group. We conclude that during CCK-8-induced
      pancreatic hypoplasia, endogenously formed nitric oxide suppresses apoptosis but
      increases cell death along non-apoptotic pathways and stimulates regeneration of
      acinar cells. Exogenous nitric oxide enhances the acinar cell turnover by
      increasing both apoptotic and non-apoptotic cell death and cell renewal. In this
      situation NF-kappaB activation seems not to inhibit apoptosis nor promote cell
      proliferation.

PMID- 15504155
TI  - In vitro cytotoxicity of epigallocatechin gallate and tea extracts to cancerous
      and normal cells from the human oral cavity.
AB  - This study compared the in vitro responses of malignant and normal cells from the
      human oral cavity to tea extracts and to its main polyphenolic component, (-)
      epigallocatechin gallate (EGCG). The antiproliferative effects of tea
      polyphenolic extracts and EGCG were more pronounced towards immortalized,
      tumourigenic (CAL27, HSC-2, and HSG(1)) and non-tumourigenic (S-G) cells than
      towards normal (GN56 and HGF-1) fibroblasts and green tea was more toxic than
      black tea. As the addition of tea extract or EGCG to cell culture medium led to
      the formation of hydrogen peroxide (H(2)O(2)), the research then focused on EGCG
      as an inducer of oxidative stress, using CAL27, the cancerous cells most
      sensitive to EGCG, HSG(1), the cancerous cells least sensitive to EGCG, and GN56
      cells. The toxicity of EGCG was decreased in the presence of catalase, an enzyme
      that degrades H(2)O(2), or of deferoxamine, a chelator of Fe(3+). Conversely,
      pretreatment of the cells with the glutathione depleters, 1-chloro-2,4
      dinitrobenzene and 1,3-bis(2-chloroethyl)-N-nitrosourea, potentiated the toxicity
      of EGCG. A 4-hr exposure to EGCG lessened the intracellular level of reduced
      glutathione in the CAL27 and HSG(1) cells, but not in the GN56 fibroblasts.
      Whereas EGCG itself did not induce lipid peroxidation, Fe(2+)-induced lipid
      peroxidation was potentiated by EGCG. A 72-hr exposure to cytotoxic
      concentrations of EGCG induced significant cytoplasmic vacuolization in all cell
      types. The results presented herein are consistent with EGCG acting as a
      prooxidant, with the cancerous cells more sensitive to oxidative stress than the
      normal cells.

PMID- 15504156
TI  - Transfusion medicine illustrated: intravascular hemolysis with brown recluse
      spider envenomation.

PMID- 15504157
TI  - Appropriate use of recombinant factor VIIa: an expanding and unanswered question.

PMID- 15504158
TI  - Triggers for switching from minipool testing by nucleic acid technology to
      individual-donation nucleic acid testing for West Nile virus: analysis of 2003
      data to inform 2004 decision making.
AB  - BACKGROUND: Concern about West Nile virus (WNV) transfusion-transmitted
      infections missed by minipool (MP) nucleic acid testing (NAT) has prompted
      consideration of the use of individual-donation (ID) NAT. Strategies were
      investigated for the application of limited ID-NAT capacity in 2004. STUDY DESIGN
      AND METHODS: Patterns of WNV MP-NAT-reactive donations tested by the Blood
      Systems Laboratory each week for 79 blood centers from June 29 to November 23,
      2003 (196 MP-NAT repeat-reactive [RR] donations among 801,697 units), were
      analyzed. ID-NAT initiation strategies were developed consisting of counts of RR
      donations and/or weekly RR rates, together with three ID-NAT discontinuation
      strategies, and ID testing burden was assessed based on these combined start and
      stop strategies. RESULTS: The effectiveness, reported as the percentage of MP-RR
      donations that would trigger ID-NAT based on each initiation strategy, ranged
      from 57 to 100 percent. The addition of a 1- or 2-week no-yield requirement for
      ID discontinuation substantially increased testing burden. Combined strategies
      resulted in projected ID-NAT of between 10 and 50 percent of donations for a 10-
      to 20-week period. For this organization, the most feasible ID-NAT initiation
      strategy was 2 MP-reactive donations and a weekly rate of 1 in 1000, which had an
      effectiveness of 81 percent and led to peak weekly ID-NAT of 20 to 25 percent of
      donations depending on the discontinuation rule. CONCLUSION: This new approach of
      targeted ID-NAT based on ongoing monitoring of MP-NAT yield may prove to be a
      rational policy for agents like WNV that cause seasonal and regional epidemics.

PMID- 15504159
TI  - Molecular and serologic tracing of a transfusion-transmitted hepatitis A virus.
AB  - BACKGROUND: The transmission of hepatitis A virus (HAV) via blood transfusion has
      not been evidenced by molecular tracing so far. CASE REPORT: A 33-year-old
      asymptomatic female volunteer made a whole-blood donation. Thirteen days later an
      acute HAV infection was diagnosed. Retrospectively, a high viral load was
      measured by quantitative reverse transcription polymerase chain reaction (RT-PCR)
      in the quarantine fresh-frozen plasma (1.4 x 10(6) geq/mL), whereas
      immunoglobulin M (IgM) and G (IgG)/IgM anti-HAV were not detectable and the
      alanine aminotransferase levels not elevated. The red blood cells have just been
      transfused on Day 14. The 63-year-old male recipient already was HAV
      seropositive. He did not develop clinical symptoms of HAV and anti-HAV IgM was
      not detected. Seventy-five days later, a 25-fold increase in the anti-HAV IgG/IgM
      titer was observed. Demonstrable HAV ribonucleic acid (RNA) in the recipient by
      means of RT-PCR on Day 6, but not on Days 1 and 75, suggests that a transient
      reinfection did occur. Analyzed sequences of the HAV RNA in the donor and
      recipient were identical. CONCLUSION: For the first time, transfusion-transmitted
      HAV was evidenced by molecular and serologic tracing. The transmitted HAV can
      survive and replicate for a limited period despite the presence of anti-HAV IgG.

PMID- 15504160
TI  - The use of recombinant activated factor VII in three patients with central
      nervous system hemorrhages associated with factor VII deficiency.
AB  - BACKGROUND: Recombinant activated factor VII (rFVIIa) is being tested to improve
      hemostasis in a variety of bleeding disorders. Clinical indications and efficacy
      are still being evaluated for this product. CASE REPORT: Over a 17-month period,
      rFVIIa was used to treat central nervous system hemorrhage in three patients who
      were found to have isolated FVII deficiency (21%, 40%, 27%). Patient A fell 30
      feet, Patient B suffered a motor vehicle accident, and Patient C had a spinal
      cord hematoma. None of the patients had a history of bleeding diathesis. All
      three patients received rFVIIa after failing initial treatment with fresh-frozen
      plasma. RESULTS: Patient A was treated with 11 doses (initial dose 95 microg/kg;
      subsequent doses 8-38 microg/kg) over 10 days; Patient B received 13 doses (45-60
      microg/kg) over 13 days; and Patient C received 5 doses (12-24 microg/kg) over 4
      days. The prothrombin time corrected from 16.2 +/- 1.8 (mean +/- SD) to 11.2 +/-
      1.6 seconds after infusion of rFVIIa, but returned to pretreatment level in 14 +/
      4 hours. At the cessation of therapy, all patients showed neurologic
      improvement. No complications related to the infusion of rFVIIa occurred.
      CONCLUSION: The use of rFVIIa may be of value both for its general effect on
      hemostasis, and specifically in the setting where there is a documented reduction
      in FVII. Doses lower than those used in patients with FVIII inhibitors appear to
      be effective in the setting of central nervous system hemorrhage.

PMID- 15504161
TI  - Clinical efficacy of postoperative autologous transfusion of filtered shed blood
      in hip and knee arthroplasty.
AB  - BACKGROUND: Total knee arthroplasty (TKA) or total hip arthroplasty (THA)
      regularly results in postoperative requirement of blood transfusion. Because of
      the disadvantages of allogeneic blood transfusion (ABT) such as the risk of
      transfusion-associated infections, incompatibility-related transfusion
      fatalities, or immunomodulatory effects, a continuing effort to reduce allogeneic
      blood transfusion is important. For this purpose, the effect of reinfusion of
      drain blood, via a postoperative wound drainage and reinfusion system, on the
      need for allogeneic blood transfusion was evaluated. STUDY DESIGN AND METHODS:
      Using a prospective observational quality assessment design, we compared 135
      patients scheduled for TKA or THA with a historic group of 96 patients. In the
      study group the Bellovac ABT autotransfusion system was used. The shed blood was
      returned either when 500 mL were collected or at most 6 hours after surgery.
      Compared were the preoperative, postoperative, and discharge hemoglobin, as well
      as the number of allogeneic blood transfusions. RESULTS: There were no
      statistical differences between preoperative, postoperative, and discharge
      hemoglobin levels. Autologous transfusion reduced the number of patients
      receiving ABT overall from 35 percent (control) to 22 percent (study). The
      decrease of allogeneic transfusion requirement was most significant after TKA:
      from 18 percent to 6 percent (p < 0.001). CONCLUSION: We conclude that the
      Bellovac ABT device reduces allogeneic blood transfusions in TKA and THA.

PMID- 15504162
TI  - Immune responsiveness against allogeneic platelet transfusions is determined by
      the recipient's major histocompatibility complex class II phenotype.
AB  - BACKGROUND: Immunoglobulin G (IgG) anti-platelet (PLT) immunity has been shown to
      be initiated by indirect allorecognition where recipient T cells recognize donor
      PLT antigens presented by class II molecules encoded by the major
      histocompatibility complex (MHC) on recipient antigen-presenting cells. To
      understand how the recipient's MHC class II molecules may influence PLT
      alloimmunity, immune responsiveness against transfused PLTs was tested in
      different mouse strains. STUDY DESIGN AND METHODS: Various inbred and mutant
      mouse strains were transfused with allogeneic PLTs and IgG donor antibodies were
      measured by flow cytometry. RESULTS: When recipient mice, expressing both MHC
      class II I-A and MHC class II I-E molecules, were transfused weekly with
      allogeneic PLTs, high titers of IgG donor antibodies were generated. In
      comparison, however, recipient mice expressing only MHC class II I-A molecules
      had significantly (p < 0.001) reduced IgG antibody responsiveness against PLT
      transfusions. The low IgG responder status against allogeneic PLT transfusions
      was rescued in transgenic mice expressing I-E molecules and in mice genetically
      deficient in either beta2-microglobulin or CD8+ T cells. CONCLUSION: IgG immune
      responsiveness against allogeneic PLT transfusions is dependent on recipient
      expression of I-E MHC class II molecules, whereas I-A expression is linked with
      CD8-mediated suppression of PLT immunity. The data suggest that strategies to
      modify recipient MHC class II presentation of donor PLT antigens would be
      effective in eliminating PLT alloimmunity.

PMID- 15504163
TI  - A McLeod phenotype detected by random screening for K:-4 [Kp(b-)] blood donors in
      Brazil.
AB  - BACKGROUND: The red blood cells of the McLeod phenotype have weak expression of
      Kell System antigens due to no expression of XK protein. STUDY DESIGN AND
      METHODS: One blood donor reacted as K:-4 [Kp(b-)] during a screening assay.
      Subsequent serologic studies demonstrated weak expression of K:4 and all other
      high-incidence Kell system antigens tested; however, no expression of Kx antigen
      was observed. RESULTS: One apparently healthy blood donor demonstrated low
      expression of K:2, K:4, K:5, K:7, K:14, K:22, and no Kx antigen in his red blood
      cells. His brother and mother showed the same weak expression, and his father
      showed normal expression of antigens tested. Flow cytometry studies confirmed the
      mother's status as a McLeod carrier female. Genotyping determined the presence of
      KEL2 and KEL4 alleles in mother and siblings. Southern blot with an exon-1 probe
      showed fragments shorter than predicted for the siblings and the mother,
      suggesting a deletion. Polymerase chain reaction with primers spanning exon 1 and
      flanking regions displayed a similar pattern. Deoxyribonucleic acid sequence
      allowed the precise characterization of a deletion of 392 bp, beginning at the 5'
      of the coding region up to nucleotide 201 of exon 1, which putatively abrogates
      the production of XK protein. CONCLUSION: Two brothers with McLeod phenotype in a
      Brazilian blood-donor population were identified. The molecular basis for this
      phenotype is a 392-bp deletion spanning from 5' of the coding region to exon 1 of
      the XK gene, never described before.

PMID- 15504164
TI  - Altered glycosylation leads to Tr polyagglutination.
AB  - BACKGROUND: Polyagglutination refers to red blood cells (RBCs) that are
      agglutinated by a high proportion of ABO-matched adult sera but not by cord sera.
      Polyagglutinable RBCs have been associated with microbial infection,
      myeloproliferative disorders, and myelodysplasia. Lectins aid in the
      identification of polyagglutination. CASE STUDY: A Hispanic male infant with mild
      hemolytic anemia, a "Bernard-Soulier-like" syndrome, intermittent neutropenia,
      mitral valve regurgitation, ligament hyperlaxity, and mild mental retardation was
      studied. The patient's Group O RBCs were polyagglutinable; they were agglutinated
      by normal human sera, several lectins [including Arachis hypogea, Salvia sclarea,
      Salvia horminum, Glycine max, Ulex europaeus, Griffonia simplicifolia I, and Gr.
      simplicifolia II], and some monoclonal antibodies. His RBCs were not agglutinated
      by cord sera, Dolichos biflorus, or Phaseolus lunatus. Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis on the RBC membranes followed by staining with
      periodic acid-Schiff stain showed markedly reduced staining of glycophorins A and
      B. Staining with Coomassie brilliant blue revealed that Band 3 has a faster
      mobility than normal. CONCLUSIONS: Collectively, the results suggest that the
      patient's RBCs have a reduction in N-acetylneuraminic acid on both N- and O
      glycans, exposing, respectively, beta1,4-galactosidase and beta1,3-galactosidase.
      The patient likely has an altered glycosyltransferase that results in defective
      glycosylation in RBCs and other cell lineages. This type of polyagglutination was
      named Tr.

PMID- 15504165
TI  - Factors affecting the efficacy of peripheral blood progenitor cells collections
      by large-volume leukaphereses with standardized processing volumes.
AB  - BACKGROUND: Peripheral blood progenitor cell (PBPC) collections should be safe
      and efficient. Therefore, the influence and risk factors in large-volume
      leukaphereses (LVL) with standardized blood volumes was investigated. STUDY
      DESIGN AND METHODS: In a total of 724 autologous LVL performed at our center,
      either 4x or 6x the patient's blood volume (PBV) was processed. The group with
      processing 4x the PBV showed a median of 31 circulating CD34+ cells per microL,
      and the group with processing 6x the PBV had a median of 13 CD34+ cells per
      microL before LVL. Individual clinical factors, laboratory factors, and apheresis
      run variables influencing the yields of PBPCs were retrospectively analyzed.
      Furthermore, the changes of laboratory variables and adverse effects during LVL
      were investigated. RESULTS: Multivariate analysis identified "age,""circulating
      CD34+ cells," and "percentage of mononuclear cells" as only factors influencing
      the yields of PBPCs. Altogether, processing 6x versus 4x the PBV did not result
      in significantly higher yields of CD34+ cells for the total group, but requested
      PBPC yields were achieved more often after processing 6x the PBV in patients
      below 20 CD34+ cells per microL blood. Processing 6x versus 4x the PBV showed a
      significant difference for the decrease of platelets, but not for any other
      laboratory variable. Adverse effects were recorded in 4.97 percent of LVL without
      accumulation in one group. CONCLUSION: In particular, patients with low amounts
      of circulating CD34+ cells profited from enlarged LVL demonstrating higher PBPC
      yields but comparable rates of adverse effects.

PMID- 15504166
TI  - Impact of ABO incompatibility on allogeneic peripheral blood progenitor cell
      transplantation after reduced intensity conditioning.
AB  - BACKGROUND: Most studies indicate that ABO incompatibility has no effect on the
      clinical outcome after allogeneic peripheral blood progenitor cell (PBPC)
      transplantation (allo-PBPCT). However, it carries additional risks of hemolytic
      reactions, delayed red blood cell (RBC) engraftment, and pure red cell aplasia
      (PRCA). Data on these events after reduced intensity conditioning (RIC) regimens
      are limited, but recent studies have suggested a higher transplant-related
      mortality (TRM) and morbidity in this setting. STUDY DESIGN AND METHODS: We
      investigated the impact of ABO-matching on the outcome of 77 patients included in
      a prospective RIC allo-PBPCT protocol, focusing on engraftment, transfusion
      requirements, graft-versus-host disease, TRM, and survival. RESULTS: There were
      17 (22%) minor and 8 (10%) major ABO-incompatible transplants. No graft failures
      were observed. After major ABO-incompatible grafts, RBC engraftment was delayed,
      longer thrombocytopenia periods were documented, and transfusion requirements
      increased. A transient mild hemolysis occurred in 10 patients, 7 (41%) minor and
      3 (37%) major ABO-mismatched. A PRCA was observed in a O+ patient with a
      pretransplant anti-Jka, grafted from an A + Jka+ donor. Graft-versus-host
      disease, disease progression, and TRM were not affected by ABO matching.
      CONCLUSION: ABO incompatibility was not associated with clinically relevant
      hemolysis after the RIC protocol used and did not impair the clinical outcome.
      PRCA was only observed in one patient, with a non-ABO RBC allo-antibody.

PMID- 15504167
TI  - Paired comparison of Gambro Trima Accel versus Baxter Amicus single-needle
      plateletpheresis.
AB  - BACKGROUND: Gambro BCT recently introduced the Trima Accel Version 5 (TR)
      plateletpheresis machine. Platelet (PLT) yields, collection efficiencies (CEs),
      numbers of white blood cells (WBCs), and processing times of the TR versus the
      Amicus (Version 2.51) single-needle (AM) procedures were evaluated by use of a
      prospective paired comparison. STUDY DESIGN AND METHODS: Target yields of 3.0 x
      10(11) to 6.8 x 10(11) PLTs in up to 100 minutes of processing time were used. To
      detect a difference of 1.0 x 10(11) PLTs with a power of 80 percent, 26 paired
      comparisons were needed. RESULTS: The mean amount of whole blood processed was
      significantly higher for TR than for AM (3795 vs. 3520 mL). The TR and AM were
      equivalent in regard to mean preprocedure PLT count (259 x 10(9) vs. 251 x
      10(9)/L), PLT yields (6.7 x 10(11) vs. 6.5 x 10(11)), split rate (65% vs. 65%),
      processing time (73 vs. 78 min), and collection rate (0.090 x 10(11) vs. 0.084 x
      10(11) PLTs/min). The TR had a significantly lower CE than the AM (76% vs. 86%).
      All of the products (after splitting) had fewer than 5 x 10(6) WBCs. CONCLUSIONS:
      The Trima Accel machine processed significantly more whole blood with equivalent
      PLT yields, processing time, and number of PLTs per minute compared to the Amicus
      single-needle procedure, but had a significantly lower CE.

PMID- 15504168
TI  - Complications of double-filtration plasmapheresis.
AB  - BACKGROUND: Double-filtration plasmapheresis (DFP) removes high-molecular-weight
      molecules semiselectively, thereby minimizing albumin loss, but with subsequent
      need for fluid substitution. The purpose of this study was to establish the
      overall incidence of complications during DFP and to analyze the possible
      contributory factors. STUDY DESIGN AND METHODS: From November 1993 to October
      2003, a total of 2502 plasmapheresis procedures were performed during 515 courses
      of plasmapheresis in 335 patients. The medical and technical records for these
      patients were reviewed. RESULTS: The overall frequency of complications was 67.5
      percent per patient, 60.0 percent per course, and 26.3 percent per procedure. The
      rate of major complications was 18.2 percent of patients, 13.2 percent of
      courses, and 2.7 percent of procedures. Hemolysis, the most common complication
      of DFP, occurred in 20 percent of patients. A total of 83 (3.3%) episodes of
      hypotension were documented in 63 patients. Vascular-access-related complications
      constituted approximately 17 percent of the total. There was one documented
      episode of clinically overt bleeding from laboratory coagulopathy necessitating
      infusion of fresh plasma to stop bleeding. There was no allergic reaction or
      mortality associated with the DFP procedures. The per-patient frequency of
      hypotension was higher in cases of chronic inflammatory neuropathy (35.1%)
      compared to the other illness categories (15.4%-17.3%), with marginal
      significance demonstrated (p = 0.0611). CONCLUSION: The safety of DFP treatment
      has been confirmed by this study. High-risk patients should be monitored
      carefully during treatment to minimize the occurrence of complications.

PMID- 15504169
TI  - Microvascular perfusion upon exchange transfusion with stored red blood cells in
      normovolemic anemic conditions.
AB  - BACKGROUND: Transfusions are intended to augment oxygen-carrying capacity. The
      ability of fresh and stored red blood cells (RBCs) to maintain microvascular
      perfusion and oxygen delivery to the tissue has not been directly measured. STUDY
      DESIGN AND METHODS: Microvascular responses to exchange transfusion with fresh
      and stored RBCs after acute isovolemic hemodilution with a plasma expander were
      investigated with the hamster window chamber model. In-vivo functional capillary
      density (FCD), blood flow, and high-resolution oxygen distribution in
      microvascular networks were measured by noninvasive methods. RESULTS: Exchange
      transfusion with an RBC suspension after a 60 percent isovolemic hemodilution
      with dextran 70 (6% MW = 70 kDa) resulted in a hematocrit of 18 percent (5.6 +/-
      0.2 g/dL hemoglobin [Hb]). All other systemic variables were unchanged. Stored
      RBCs (28 days in citrate-phosphate-dextrose-adenine-1) resuspended in fresh
      frozen plasma matched to the Hct and Hb concentration were exchange transfused
      until 25 percent of the circulating RBCs were stored RBCs. Stored RBCs reduced
      microvascular flow and FCD by 63 and 54 percent, respectively, of the level
      achieved when fresh RBCs were exchange transfused. Microvascular oxygen
      extraction by the stored RBC was 54 percent lower than that of the fresh RBCs.
      The tissue oxygen levels were 3.5 and 14.4 mmHg for the stored and fresh RBCs,
      respectively. CONCLUSION: Circulation of stored RBCs in a hemodiluted animal
      resulted in significantly malperfused and underoxygenated microvasculature that
      was not detectable at the systemic level.

PMID- 15504170
TI  - Severe hemolysis resulting from D incompatibility in a case of ABO-identical
      liver transplant.
AB  - BACKGROUND: Hemolysis due to D incompatibility in the setting of liver
      transplantation is less frequent than that associated with ABO incompatibility,
      but can represent an equally adverse event. Approximately 10 percent of ABO
      compatible liver transplants involve a D- donor and a D+ recipient. CASE REPORT:
      A case of severe D incompatibility resulting from liver transplantation in a 50
      year-old O Rh+ man with end-stage liver disease who received an O Rh- liver
      allograft is reported. A declining hemoglobin level complicated the patient's
      postoperative course with laboratory evidence of anti-D-mediated hemolysis.
      Investigations revealed that the transplanted liver was from a female O Rh- donor
      with detectable antibodies against D, C, and K. The severity of the hemolytic
      anemia was such that the patient required two separate red blood cell (RBC)
      exchanges and intermittent RBC transfusions over the course of almost a year. In
      addition to the use of RBCs negative for D, C, and K, the patient underwent a
      variety of B-cell suppressive therapies including glucocorticosteroids,
      mycophenolate mofetil, and rituximab. A normalization of hemoglobin levels and a
      decrease in serum bilirubin did not occur until after a splenectomy on
      postoperative Day 321. CONCLUSION: This represents the sixth and most severe case
      reported of hemolysis resulting from D incompatibility in liver transplantation.
      When unexpected serologic findings are identified in a transplant recipient,
      obtaining more information on the donor may help guide transfusion support.

PMID- 15504171
TI  - Patterns of age- and sex-specific prevalence of major blood-borne infections in
      United States blood donors, 1995 to 2002: American Red Cross blood donor study.
AB  - BACKGROUND: The American Red Cross has been maintaining a research database of
      all blood donations, including all testing results for infectious disease
      markers, since 1995. This study analyzes the temporal trends of major blood-borne
      infections among blood donors. STUDY DESIGN AND METHODS: Temporal trends for age-
      and sex-specific prevalence of human immunodeficiency virus (HIV), hepatitis B
      virus (HBV), hepatitis C virus (HCV), and syphilis infections in US blood donors
      were analyzed based on linear trend or time series model or other models as
      appropriate. RESULTS: From 1995 to 2002, significant declines have been observed
      for infections that used to be at relatively higher levels. Declines in
      prevalence were slower among first-time donations than repeat donations. There
      was an increase in prevalence of anti-HCV among first-time male donors of 50 to
      59 years of age. Anti-HIV prevalence appeared to have increased among first-time
      male donors of 30 to 39 years of age since 2000. CONCLUSION: Different sex and
      age groups showed various patterns of decline and even signs of increase. The
      increasing prevalence among some age and sex groups may merit further
      investigation.

PMID- 15504172
TI  - An examination of hospital satisfaction with blood suppliers.
AB  - BACKGROUND: The purpose of this study was to identify factors that predict
      overall hospital satisfaction with blood suppliers. STUDY DESIGN AND METHODS: The
      data for this study came from a 2001 satisfaction survey of hospital blood bank
      managers conducted by the National Blood Data Resource Center. A total of 1325
      blood-utilizing hospitals were included in the final study database. The
      measurement of hospital satisfaction with its blood supplier encompasses the five
      composites of the SERVQUAL model. The five composites are 1) tangibles, 2)
      reliability, 3) responsiveness, 4) assurance, and 5) empathy. Linear regression
      was performed with overall hospital satisfaction as the dependent variable and
      the five composites of the SERVQUAL model and control variables as predictors of
      overall hospital satisfaction with blood suppliers. RESULTS: Significant
      predictors of hospital satisfaction with blood suppliers are satisfaction with
      medical and clinical support provided by the blood center, satisfaction with the
      routine delivery schedule, and price (service fee) of red cells. CONCLUSION:
      Prior studies have demonstrated the importance of customer satisfaction to
      organizations. As organizations, blood centers can benefit from improved
      satisfaction from their hospital customers. Blood center strategies that focus on
      improving these three predictors of overall hospital satisfaction with primary
      blood suppliers will be the most likely to improve and/or maintain hospital
      customer satisfaction with primary blood suppliers.

PMID- 15504173
TI  - Extended storage of AS-1 and AS-3 leukoreduced red blood cells for 15 days after
      deglycerolization and resuspension in AS-3 using an automated closed system.
AB  - BACKGROUND: The utilization of cryopreserved red blood cell (RBC) units had been
      limited by a maximum postdeglycerolization storage of 24 hours at 1 to 6 degrees
      C until the recent development of a closed system for the glycerolization and
      deglycerolization process. STUDY DESIGN AND METHODS: Sixty leukoreduced additive
      solution (AS), AS-1 (n = 30) and AS-3 (n = 30) RBC units from 500-mL whole blood
      (WB) collections were stored for 6 days, glycerolized, frozen at -70 +/- 5
      degrees C for at least 14 days, thawed, deglycerolized, and stored for 15 days at
      1 to 6 degrees C. Glycerolization and deglycerolization were performed with the
      ACP 215. In-vitro variables were tested before glycerolization, on Day 0, and Day
      15 after deglycerolization storage. Forty donors were assessed for double-label
      24-hour percent recovery, and T1/2 survival time was measured for 20 donors.
      RESULTS: Postdeglycerolization mean +/- standard deviation in-vitro RBC mass
      recoveries were 93 +/- 5 percent for AS-1 and 95 +/- 4 percent for AS-3. Mean
      hemoglobin +/- standard deviation after deglycerolization was 50.5 +/- 5.5g for
      AS-1 and 50.1 +/- 3.5g for AS-3. Mean hemolysis (Day 15) was 0.36 +/- 0.11
      percent for AS-1 and 0.38 +/- 0.13 percent for AS-3. Double-label 24-hour in-vivo
      recoveries were 82.5 +/- 7.8 percent for AS-1 and 81.4 +/- 7.1 percent for AS-3.
      The 51Cr T1/2 value was 41.8 +/- 3.97 for AS-1 and 40.6 +/- 7.11 for AS-3. Other
      in-vitro variables were as expected. CONCLUSION: Leukoreduced AS-1 and AS-3 RBCs
      after frozen storage at -70 +/- 5 degrees C can be stored for up to 14 days when
      processing is performed with the ACP 215 system with resuspension of
      deglycerolized RBCs in AS-3.

PMID- 15504174
TI  - The Rh blood group system in review: a new face for the next decade.

PMID- 15504175
TI  - Is fresh frozen plasma overtransfused in the United States?

PMID- 15504177
TI  - Leukoreduction and postoperative infections.

PMID- 15504179
TI  - Corticosteroids in postoperative pain management: future research directions for
      a multifaceted therapy.

PMID- 15504180
TI  - Methylprednisolone intravenously 1 day after surgery has sustained analgesic and
      opioid-sparing effects.
AB  - BACKGROUND: In previous studies on glucocorticoids for postoperative pain, the
      test drug has been given perioperatively, usually before measurement of baseline
      pain. In order to evaluate the time course and magnitude of the analgesic effect
      of a glucocorticoid in well-established postoperative pain, we compared
      methylprednisolone with ketorolac and placebo, after assessment of baseline pain
      on the first postoperative day. METHODS: This was a double-blind, single dose,
      randomized, parallel comparison of intravenous (i.v.) methylprednisolone 125 mg,
      ketorolac 30 mg as an active control, and placebo in 75 patients with moderate to
      severe pain 1 day after orthopaedic surgery. Outcome variables were pain
      intensity (0-100 VAS), pain relief (0-4 PAR) and rescue opioid consumption.
      RESULTS: Methylprednisolone was not significantly different from ketorolac and
      gave significantly lower pain intensity from 1 h (0-6 h, P < 0.02), and more pain
      relief 2-6 h after test drugs (P < 0.05) compared with placebo. After 24 h, pain
      intensity was lower in both active drug groups compared with placebo
      (methylprednisolone, P < 0.0001; ketorolac, P < 0.007). Number needed to treat
      (NNT) calculated from patients having more than at least 50% of maximum
      obtainable total pain relief during the first 6 h (>50%maxTOTPAR(6 h)) was 3.6
      for methylprednisolone and 3.1 for ketorolac. Number needed to treat calculated
      from the percentage reporting at least 50% pain relief for at least 4 h
      (>50%PAR(4 h)) was 2.8 for both groups. Opioid consumption was significantly
      reduced for 72 h after methylprednisolone compared with ketorolac (P < 0.02) and
      placebo (P < 0.003). CONCLUSION: Methylprednisolone 125 mg i.v. 1 day after
      surgery gave similar early reduction of pain as i.v. ketorolac 30 mg. Less pain
      than placebo 24 h after methylprednisolone, and lower opioid consumption for 72 h
      compared with ketorolac and placebo indicate sustained analgesic effects of
      methylprednisolone.

PMID- 15504181
TI  - The 118 A > G polymorphism in the human mu-opioid receptor gene may increase
      morphine requirements in patients with pain caused by malignant disease.
AB  - BACKGROUND: Dispositions for genes encoding opioid receptors may explain some
      variability in morphine efficacy. Experimental studies show that morphine and
      morphine-6-glucuronide are less effective in individuals carrying variant alleles
      caused by the 118 A > G polymorphism in the mu-opioid receptor gene (OPRM1). The
      purpose of the study was to investigate whether this and other genetic
      polymorphisms in OPRM1 influence the efficacy of morphine in cancer pain
      patients. METHODS: We screened 207 cancer pain patients on oral morphine
      treatment for four frequent OPRM1 gene polymorphisms. The polymorphisms were the 
      172 G > T polymorphism in the 5'untranslated region of exon 1, the 118 A > G
      polymorphism in exon 1, and the IVS2 + 31 G > A and IVS2 + 691 G > C
      polymorphisms, both in intron 2. Ninety-nine patients with adequately controlled
      pain were included in an analysis comparing morphine doses and serum
      concentrations of morphine and morphine metabolites in the different genotypes
      for the OPRM1 polymorphisms. RESULTS: No differences related to the -172 G > T,
      the IVS2 + 31 G > A and the IVS2 + 691 G > C polymorphisms were observed.
      Patients homozygous for the variant G allele of the 118 A > G polymorphism (n =
      4) needed more morphine to achieve pain control, compared to heterozygous (n =
      17) and homozygous wild-type (n = 78) individuals. This difference was not
      explained by other factors such as duration of morphine treatment, performance
      status, time since diagnosis, time until death, or adverse symptoms. CONCLUSION:
      Patients homozygous for the 118 G allele of the mu-opioid receptor need higher
      morphine doses to achieve pain control. Thus, genetic variation at the gene
      encoding the mu-opioid receptor contributes to variability in patients' responses
      to morphine.

PMID- 15504182
TI  - Low-dose bupivacaine with sufentanil prevents hypotension after spinal anesthesia
      for hip repair in elderly patients.
AB  - BACKGROUND: Hip fracture is common in the geriatric population. Patients in this
      group are often at high risk for perioperative complications from concurrent
      diseases. Conventional spinal anesthesia can be associated with hypotension but
      has a better postoperative outcome compared to general anesthesia. We judged that
      a reduced dose of bupivacaine in combination with sufentanil could give reliable
      blocks with minimal hypotension. METHODS: Fifty elderly patients were randomized
      into two groups. The study group received spinal anesthesia as a combination of
      hyperbaric bupivacaine 7.5 mg and sufentanil 5 microg while the control group
      received hyperbaric bupivacaine 15 mg. The hemodynamic stability of the patients
      and the quality of the blocks were compared. RESULTS: All patients had adequate
      duration of reliable blocks. More control group patients than study group
      patients required ephedrine due to hypotension. CONCLUSION: A reduced dose of
      hyperbaric bupivacaine (7.5 mg) in combination with sufentanil (5 microg)
      provides reliable spinal anesthesia for the repair of hip fracture in aged
      patients with few events of hypotension and little need for vasopressor support
      of blood pressure.

PMID- 15504183
TI  - Women report more pain on injection of a precurarization dose of rocuronium: a
      randomized, prospective, placebo-controlled trial.
AB  - BACKGROUND: The purpose of this study was to investigate whether gender
      influences the perception of pain on injection of rocuronium. METHODS: In this
      prospective, placebo-controlled trial 120 patients were randomized into four
      groups to receive rocuronium 0.03 mg kg(-1) (40 female and 40 male patients) or
      saline (20 female and 20 male patients). The incidence and severity of the
      injection pain after administration of the study drug was compared between female
      and male patients using a numerical rating scale (0-10). Signs of local
      irritation, i.e. erythema and thrombophlebitis, were assessed up to 48 h after
      surgery. RESULTS: In 26 (32.5%) of the 80 patients receiving rocuronium, pain on
      injection was observed. This occurred significantly more frequently in the female
      compared with male patients: 18 (45%) vs. eight (20%), respectively (P = 0.032).
      The severity was more pronounced in the women than in the men (P = 0.020). The
      incidence of the rocuronium-associated pain was significantly increased compared
      with the Saline groups (P < 0.001). After surgery no patient complained of any
      residual pain and no local signs were observed in any patient during the study
      period. CONCLUSIONS: Women experienced more pain on injection of rocuronium than
      men, moreover this is an additional evidence for gender-related differences in
      pain perception. When rocuronium is used as a precurarization agent, an analgesic
      pretreatment (e.g. opioids) should be considered, especially for female patients.

PMID- 15504184
TI  - Intrathecal adenosine increases spinal cord blood flow in the rat: measurements
      with the laser-Doppler flowmetry technique.
AB  - BACKGROUND: Adenosine and adenosine analogues induce antinociception both after
      systemic and intrathecal (i.t.) administration in animal models. Further,
      patients with neuropathic pain have been treated successfully with i.t.
      adenosine. Prior to introducing new analgesic drugs for regular spinal use in
      humans, experimental studies must be undertaken to evaluate the risks of
      neurotoxicity. It is important to evaluate the possibility of cytotoxic effects
      and that antinociception may be due to decreased spinal cord blood flow (SCBF)
      and neural ischaemia. The present study evaluates whether adenosine or isotonic
      mannitol induces changes in SCBF as assessed by laser-Doppler flowmetry (LDF).
      METHODS: After laminectomy and insertion of i.t. catheters, seven rats received
      adenosine 50 microg in isotonic mannitol 500 microg, six rats received isotonic
      mannitol 500 microg and eight rats received saline 0.9%. SCBF was registered by
      the LDF technique continuously for 3 h after injection. Arterial blood pressure
      was also assessed. RESULTS: In the adenosine in mannitol group, SCBF increased up
      to 230% of baseline levels for almost 40 min, P = 0.044 and then declined. In the
      mannitol group, SCBF increased up to 180% of baseline (P < 0.011) before
      declining. At 60 min, SCBF had returned to saline levels and remained stable
      during the rest of the experiment. CONCLUSION: Intrathecal administration of
      adenosine in mannitol and of mannitol both increased SCBF in rats, compared with
      saline. It is unlikely that the effects on SCBF induced by adenosine and mannitol
      could result in neurotoxicity of the spinal cord.

PMID- 15504185
TI  - Comparison of the analgesic efficacy of ketobemidone and morphine for management
      of postoperative pain in children: a randomized, controlled study.
AB  - BACKGROUND: Ketobemidone has been used as an analgesic for postoperative pain in
      children, but to our knowledge the effect and occurrence of adverse effects of
      ketobemidone compared to morphine is not known. The aim was to determine if the
      analgesic potency and the occurrence of adverse effects of ketobemidone differ
      from morphine when administered to children, as measured by patient-controlled
      analgesia consumption (PCA) for postoperative pain. METHODS: Sixty healthy
      children, aged 6 to 16 years, scheduled for elective surgery were randomized to
      receive either ketobemidone (Ke) 1 mg ml(-1) or morphine (Mo) 1 mg ml(-1) for
      postoperative pain through PCA. Drug consumption (microg kg(-1) h(-1)), the
      number of PCA doses, pain intensity, and adverse effects were recorded at regular
      intervals. RESULTS: Data on total drug consumption were based on 26 children in
      the Ke group and 28 in the Mo group. A non-statistically significant difference
      for total mean consumption of ketobemidone (18.6 microg kg(-1)h(-1)) and morphine
      (23.2 microg kg(-1)h(-1)) was obtained. The mean dose ratio (Mo/Ke) was 0.80 and
      the median was 0.94. Children's characteristics, loading dose, PCA doses, VAS
      scores, and adverse effects showed no significant differences between the groups.
      CONCLUSION: The analgesic potency and adverse effects of ketobemidone are similar
      to morphine when used for postoperative pain management in children.

PMID- 15504186
TI  - Pitfalls and challenges when assessing the depth of hypnosis during general
      anaesthesia by clinical signs and electronic indices.
AB  - The objective of this article was to review the present methods used for
      validating the depth of hypnosis. We introduce three concepts, the real depth of
      hypnosis (DHreal), the observed depth of hypnosis (DHobs), and the electronic
      indices of depth of hypnosis (DHel-ind). The DHreal is the real state of hypnosis
      that the patient has in a given moment during the general anaesthesia. The DHobs
      is the subjective assessment of the anaesthesiologist based on clinical signs.
      The DHel-ind is any estimation of the depth of hypnosis given by an electronic
      device. The three entities DHreal, DHobs and DHel-ind should in the ideal
      situation be identical. However, this is rarely the case. The correlation between
      the DHobs and the DHel-ind can be affected by a number of factors such as the
      stimuli used for the assessment of the level of consciousness or the
      administration of analgesic agents or neuro muscular blocking agents. Opioids,
      for example, can block the response to tactile and noxious stimuli, and even the
      response to verbal command could vanish, hence deeming the patient in a lower
      depth of hypnosis than the real patient state. The DHel-ind can be disturbed by
      the presence of facial muscular activity. In conclusion, although several
      monitors and clinical scoring scales are available to assess the depth of
      hypnosis during general anaesthesia, care should be taken when interpreting their
      results.

PMID- 15504187
TI  - Effects of subanaesthetic and anaesthetic doses of sevoflurane on regional
      cerebral blood flow in healthy volunteers. A positron emission tomographic study.
AB  - BACKGROUND: We tested the hypothesis that escalating drug concentrations of
      sevoflurane are associated with a significant decline of cerebral blood flow in
      regions subserving conscious brain activity, including specifically the thalamus.
      METHODS: Nine healthy human volunteers received three escalating doses using
      0.4%, 0.7% and 2.0% end-tidal sevoflurane inhalation. During baseline and each of
      the three levels of anaesthesia one PET scan was performed after injection of .
      Cardiovascular and respiratory parameters were monitored and
      electroencephalography and bispectral index (BIS) were registered. RESULTS:
      Sevoflurane decreased the BIS values dose-dependently. No significant change in
      global cerebral blood flow (CBF) was observed. Increased regional CBF (rCBF) in
      the anterior cingulate (17-21%) and decreased rCBF in the cerebellum (18-35%)
      were identified at all three levels of sedation compared to baseline. Comparison
      between adjacent levels sevoflurane initially (0 vs. 0.2 MAC) decreased rCBF
      significantly in the inferior temporal cortex and the lingual gyrus. At the next
      level (0.2 MAC vs. 0.4 MAC) rCBF was increased in the middle temporal cortex and
      in the lingual gyrus, and decreased in the thalamus. At the last level (0.4 MAC
      vs. 1 MAC) the rCBF was increased in the insula and decreased in the posterior
      cingulate, the lingual gyrus, precuneus and in the frontal cortex. CONCLUSION: At
      sevoflurane concentrations at 0.7% and 2.0% a significant decrease in relative
      rCBF was detected in the thalamus. Interestingly, some of the most profound
      changes in rCBF were observed in structures related to pain processing (anterior
      cingulate and insula).

PMID- 15504188
TI  - Similar excitation after sevoflurane anaesthesia in young children given rectal
      morphine or midazolam as premedication.
AB  - BACKGROUND: Sevoflurane is a rapid-acting volatile anaesthetic agent frequently
      used in paediatric anaesthesia despite transient postoperative symptoms of
      cerebral excitation, particularly in preschool children. This randomised and
      investigator-blinded study was designed to evaluate whether premedication with an
      opioid might reduce non-divertible postoperative excitation more than
      premedication with a benzodiazepine in preschool children anaesthetized with
      sevoflurane. METHODS: Ninety-two healthy two to six year-old children scheduled
      for nasal adenoidectomy were randomised to be given rectal atropine 0.02 mg kg(
      1) together with either morphine 0.15 mg kg(-1) or midazolam 0.30 mg kg(-1)
      approximately 30 min before induction and maintenance of sevoflurane anaesthesia.
      The patient groups were compared pre- and postoperatively by repeated clinical
      assessments of cerebral excitation according to a modified Objective Pain
      Discomfort Scale, OPDS. RESULTS: There were no statistically significant
      postoperative differences in incidence, extent or duration of excitation between
      children given morphine or midazolam for premedication, whereas morphine was
      associated with more preoperative excitation than was midazolam. The study groups
      did not differ significantly with respect to age, weight, duration of surgery and
      anaesthesia, and time from tracheal extubation to arrival in and discharge from
      the postoperative ward. CONCLUSION: In this study morphine for premedication in
      young children anaesthetized with sevoflurane was associated with similar
      postoperative and higher preoperative OPDS scores compared with midazolam. These
      findings indicate that substitution of morphine for midazolam is no useful way of
      reducing clinical excitation after sevoflurane anaesthesia.

PMID- 15504189
TI  - Betamethasone does not prevent nausea and vomiting induced by ipecacuanha.
AB  - BACKGROUND: Corticosteroids reduce the incidence of PONV but the mode of action
      is not known. The purpose of this study was to evaluate if betamethasone has
      serotonin (5-HT) antagonistic effects. Ipecacuanha is known to release serotonin
      and therefore it was used to induce nausea and vomiting. The 5-HT3 antagonist
      ondansetron was used as a control substance. METHODS: In a randomized, double
      blind, cross-over, placebo-controlled study 10 healthy male and female volunteers
      (6 M/4F), mean age 19.5 (18-23) years, mean weight 69.7 (53-84) kg, were studied
      on three occasions separated by at least 1 week. They were randomly allocated to
      receive pretreatment with betamethasone 8 mg, ondansetron 8 mg, or normal saline
      2 ml as placebo on each occasion, 15 min before oral ingestion of 30 ml of
      Ipecacuanha syrup. After ingestion of ipecacuanha, vomitings were recorded and
      the intensity of nausea was estimated with a visual analog scale during 2 h.
      RESULTS: During the first 2 h after ingestion of ipecacuanha nine of the 10
      volunteers vomited both after betamethasone and placebo. No volunteer vomited
      after ondansetron (P < 0.01 vs. betamethasone and placebo). The max VAS for
      nausea was significantly higher after betamethasone and placebo compared to
      ondansetron (P < 0.01). There were no statistically significant differences of
      the max VAS for nausea between betamethasone and placebo. CONCLUSION: This study
      in volunteers has shown that betamethasone does not prevent nausea and vomiting
      induced by oral intake of ipecacuanha syrup. As ipecacuanha releases 5
      hydroxytryptamin, it can be concluded that betamethasone does not have 5-HT3
      antagonistic effects.

PMID- 15504190
TI  - Dixyrazine for the prevention of postoperative nausea and vomiting after
      laparoscopic cholecystectomy.
AB  - BACKGROUND: The study assessed the efficacy and safety of dixyrazine, an
      alternative neuroleptic drug to droperidol, in the prophylaxis of postoperative
      nausea and vomiting (PONV). METHODS: A total of 197 patients scheduled for
      laparoscopic cholecystectomy under general anesthesia were randomized to receive
      either dixyrazine 10 mg or placebo double-blinded at the end of surgery. Scores
      pertaining to PONV episodes, analgetic supply, rescue medication, adverse events
      and patient satisfaction were collected over the first 2 h in the PACU and the
      next 22 h in the ward. RESULTS: The incidence of PONV over the entire 24-h period
      was reduced from 32% in the placebo group to 13% in the dixyrazine group (P< or
      =0.004). The incidence of nausea in the first 2 h was reduced from 15% in the
      placebo group to 4% in the dixyrazine group (P< or =0.02) and from 12% to 5% in
      the next 22 h. The incidence of emetic episodes was not different between the two
      groups. Postoperative shivering was significantly less prevalent in the
      dixyrazine than in the placebo group (2% vs. 13%; P< or =0008), and opioid
      analgesics were required significantly less often (61% vs. 75%; P< or =0.01). No
      significant adverse effects were observed. Patient satisfaction was similar in
      both groups. CONCLUSION: Prophylactic dixyrazine is an effective, safe, and cheap
      antiemetic drug for laparoscopic cholecystectomy without involving any
      significant adverse events.

PMID- 15504191
TI  - Clonidine vs. midazolam as premedication in children undergoing adeno
      tonsillectomy: a prospective, randomized, controlled clinical trial.
AB  - BACKGROUND: Clonidine administration in the setting of paediatric anaesthesia is
      associated with a number of desirable effects, e.g. preoperative sedation,
      analgesia and reduced anaesthetic requirements. The aim of the current study was
      to compare postoperative outcome variables using a prospective, randomized,
      double-blind design after premedication with clonidine or midazolam. METHODS: One
      hundred paediatric ASA physical status 1 patients (age 1-11 year) scheduled for
      adeno-tonsillectomy were assigned to receive rectal premedication with midazolam
      (300 microg kg(-1) and atropine 40 microg kg(-1); group M, n = 52) or clonidine
      (5 microg kg(-1 and) atropine 40 microg kg(-1); group C, n = 48) prior to a
      standardized sevoflurane anaesthetic. The incidence of immediate postoperative
      pain (0-2 h), as assessed by repeated Objective Pain Scale (OPS) scores, was
      chosen as the primary end-point of the study. Degree of sedation (modified
      Vancouver sedation scale 0-3), occurrence of postoperative vomiting (POV), and
      incidence of shivering and immediate postoperative confusion were registered as
      secondary end-points. After hospital discharge parents were instructed to
      continue the evaluation of pain, sedation, POV and sleep pattern during a 24-h
      period. Parents were also asked for their preference concerning the postoperative
      behaviour of their child (calm, sedated vs. alert, active). RESULTS: In the early
      postoperative period patients in the clonidine group had a significantly lower
      sum of 5 OPS scores (median = 8.0) compared to group M (median = 11.5) (P =
      0.011). Administration of clonidine was also associated with a slightly higher
      sum of sedation scores (median = 13) in the early postoperative period compared
      to children receiving midazolam (median = 12) (P < 0.001). No episode of
      shivering was observed in the clonidine group but was present in five of the
      patients in the midazolam group (P = 0.057). In younger children (< 5 years) the
      incidence of postoperative confusion was lower in the clonidine group (P =
      0.001). No difference in the frequencies of POV incidences, degree of
      postoperative pain, need for analgesics, or sleep pattern during the first 24
      postoperative hours could be observed between the groups according to the
      parental evaluation. Children premedicated with clonidine were more calm and
      sedated compared to children in the midazolam group (P = 0.024) as judged by
      their parents. A significant majority of parents (75%; P < 0.001) preferred a
      calm and sedated child during the first postoperative 24-h period. CONCLUSION:
      Rectal premedication with clonidine was associated with a significant reduction
      of pain in the early postoperative period compared to midazolam and was also
      associated with moderately increased sedation during the first 24 postoperative
      hours. The sedative effect of clonidine is in agreement with the unambiguous
      finding of a parental preference for a calm and sedated child during the first 24
      postoperative hours.

PMID- 15504192
TI  - Rocuronium attenuates oculocardiac reflex during squint surgery in children
      anesthetized with halothane and nitrous oxide.
AB  - BACKGROUND: The oculocardiac reflex (OCR) may be activated during squint surgery.
      The aim of this study was to test whether rocuronium 0.4 mg kg(-1) could reduce
      the frequency of OCR, and also whether a single dose of succinylcholine 1 mg kg(
      1) could affect the frequency of OCR during anesthesia with halothane in a
      nitrous oxide/oxygen mixture. METHODS: A total of 161 ASA I children, 3-10 years
      old, undergoing elective surgery of the medial rectus muscle (MRM) were randomly
      assigned to three groups. Group R (n = 51), received 0.4 mg kg(-1) of rocuronium
      intravenously before endotracheal intubation. Group S (n = 58) received 1 mg kg(
      1) of succinylcholine. Group C (controls, n = 52) received no relaxant.
      Oculocardiac reflex was defined as a reduction in heart rate (HR) > or = 15%
      and/or the appearance of any other arrhythmias, during manipulation of the MRM.
      Analysis of variance (anova), chi-squared, Kruskal-Wallis, and Student's t-tests
      were used for statistical analysis; P< 0.05 was considered statistically
      significant. RESULTS: In group R, OCR occurred in 15/51 (29%) of children, in
      group S in 31/58 (53%), and in group C in 23/52 (44%) (chi2 = 6.46, P = 0.049).
      In group R, the incidence of arrhythmias such as nodal rhythms, supraventricular
      and ventricular premature beats was 6%, compared with 22% in group S and 19% in
      group C (chi2 = 6.01, P = 0.040). However, there was no reduction in the
      occurrence of bradycardia (chi2 = 0.16, P = 0.924). CONCLUSION: Rocuronium
      reduced the frequency of OCR, mainly by reducing the incidence of
      supraventricular and ventricular premature beats.

PMID- 15504193
TI  - Effect of ephedrine on the onset time of succinylcholine.
AB  - BACKGROUND: The aim of this study was to evaluate the effect of ephedrine
      administered prior to induction of anaesthesia on the onset time of
      succinylcholine for endotracheal intubation. METHODS: Patients were randomly
      assigned to receive intravenously (i.v.) either 70 microg kg(-1) of ephedrine
      (Group I; n = 25) or saline (Group II; n = 25) 3 min before induction of
      anaesthesia. Induction of anaesthesia was provided with propofol 2 mg kg(-1) plus
      remifentanil 1 microg kg(-1). Onset time and duration of muscle fasciculation and
      onset time of succinylcholine were recorded. Intubation was attempted after
      establishment of 100% thumb relaxation and difficulties were recorded. Heart
      rate, pulse oxymetry (SpO2) and mean arterial pressure (MAP) were also recorded.
      RESULTS: The onset time of succinylcholine were significantly (P < 0.001) shorter
      in Group I (26 +/- 4 s), when compared with Group II (43 +/- 6 s). Patients in
      Group I were intubated at 49 +/- 7 s compared with 68 +/- 10 s in Group II. The
      score of intubation was similar in both groups. Duration of muscle fasciculation
      was longer in Group II. Heart rate and MAP increased significantly (P < 0.05)
      after ephedrine injection, compared with the baseline value in Group I.
      CONCLUSIONS: The onset time of succinylcholine can be shortened with ephedrine
      pretreatment.

PMID- 15504194
TI  - Further commentary on Denmark's 1952-53 poliomyelitis epidemic, especially
      regarding mortality; with a correction.
AB  - Berthelsen and Cronqvist recently published an article in Acta Anaesthesiologica
      Scandinavica including aspects which could lead on to further discussion about
      the Danish 1952-53 poliomyelitis epidemic. This paper considers how Bjorn Ibsen's
      initial approach to treatment during the epidemic was successful, as well as how
      it could have failed; the roles played by ventilatory failure vs. gross
      neurologic destruction in causing deaths; and compilations from publications of
      statistics concerning mortality of the epidemic. The Blegdam Hospital concept of
      'life-threatening poliomyelitis' is revisited, along with its division into six
      anatomico-clinical categories for the 345 patients so classified. Attention is
      drawn to the severity of assorted cerebral lesions demonstrated in 114 of the 115
      autopsies conducted from the 144 fatal cases. Despite an overall mortality rate
      of 41.6% among the entire epidemic's sickest patients, a lowest mortality rate of
      11% in the last 18 of such patients is identified. Note is made of the difficulty
      in reconciling various sources for certain features -- for which the 1956 book on
      the epidemic, edited by H.C.A. Lassen, has been freely used. Some folklore about
      aspects of management is mentioned. In the light of other recent research by Dr
      Berthelsen an essential correction is needed in dating 'Bjorn Ibsen's Day',
      amending 26 August 1952 to the 27th.

PMID- 15504195
TI  - Adverse biochemical and physiological effects of prostacyclin in experimental
      brain oedema.
AB  - BACKGROUND: Prostacyclin (PGI2) and its stable analogues are known to reduce
      capillary hydraulic permeability. This study explores the biochemical and
      physiological effects of i.v. infusion of low-dose PGI2 in an experimental model
      of vasogenic brain oedema. METHODS: Twenty-seven anaesthetized and mechanically
      ventilated piglets with brain oedema induced by intrathecal injection of
      lipopolysaccharide (LPS) were used. Five of the animals received a continuous
      infusion of PGI2 (1 ng kg(-1) min(-1)) i.v. Four microdialysis catheters were
      placed in the brain to measure interstitial concentrations of glucose, lactate,
      and glycerol. Mean arterial pressure (MAP), intracranial pressure (ICP) and
      temperature were monitored continuously. Low-dose infusion of PGI2 started 1 h
      before the LPS injection and was constant during the study period. RESULTS:
      Intracranial pressure increased significantly in animals treated with PGI2. The
      increase in ICP was associated with significant cerebral biochemical changes:
      decrease in glucose, increase in lactate, increase in lactate/glucose ratio and
      increase in glycerol. CONCLUSION: In LPS-induced brain oedema i.v. infusion of
      low-dose PGI2 caused a further increase in ICP and a perturbation of energy
      metabolism, indicating cerebral ischemia and degradation of cellular membranes.

PMID- 15504196
TI  - Thermodilution cardiac output--are three injections enough?
AB  - BACKGROUND: Bolus thermodilution cardiac output measurements have been a mainstay
      in clinical monitoring of critically ill patients for more than 30 years. Usually
      the results of an arbitrarily chosen number (1-6) of thermal indicator injections
      are averaged to increase the reliability of the measurement. The number of
      injections needed to achieve a given level of precision has, however, not
      previously been systematically investigated. METHODS AND RESULTS: In 80
      hemodynamically stable patients cardiac output was determined as the average of
      eight injections of 10 ml of iced saline. From the 638 measurements we examined
      the relationship between the number of thermal indicator injections and the
      precision of the resulting cardiac output estimate. Furthermore, the association
      between the number of injections and the least detectable difference among two
      sets of measurements was established. CONCLUSION: The current study shows that
      one needs to average the results of four injections to be 95% confident that the
      result is within 5% of the 'true' cardiac output and that two series of four
      measurements have to differ by at least 7% before one can be sure (95%) that a
      change in cardiac function has taken place.

PMID- 15504197
TI  - Fluid resuscitation from severe hemorrhagic shock using diaspirin cross-linked
      hemoglobin fails to improve pancreatic and renal perfusion.
AB  - BACKGROUND: Fluid resuscitation from hemorrhagic shock is intended to abolish
      microcirculatory disorders and to restore adequate tissue oxygenation. Diaspirin
      cross-linked hemoglobin (DCLHb) is a hemoglobin-based oxygen carrier (HBOC) with
      vasoconstrictive properties. Therefore, fluid resuscitation from severe
      hemorrhagic shock using DCLHb was expected to improve perfusion pressure and
      tissue perfusion of kidneys and pancreas. METHODS: In 20 anesthetized domestic
      pigs with an experimentally induced coronary stenosis, shock (mean arterial
      pressure 45 mmHg) was induced by controlled withdrawal of blood and maintained
      for 60 min. Fluid resuscitation (replacement of the plasma volume withdrawn
      during hemorrhage) was performed with either 10% DCLHb (DCLHb group, n = 10) or
      8% human serum albumin (HSA) oncotically matched to DCLHb (HSA group, n = 10).
      Completion of resuscitation was followed by a 60-min observation period. Regional
      blood flow to the kidneys and the pancreas was measured by use of the radioactive
      microspheres method at baseline, after shock and 60 min after fluid
      resuscitation. RESULTS: All animals (10/10) resuscitated with DCLHb survived the
      60-min observation period, while 5/10 control animals died within 20 min due to
      persisting subendocardial ischemia. In contrast to HSA survivors, pancreas and
      kidneys of DCLHb-treated animals revealed lower total and regional organ
      perfusion and regional oxygen delivery. Renal and pancreatic blood flow
      heterogeneity was higher in the DCLHb group. CONCLUSION: DCLHb-induced
      vasoconstriction afforded superior myocardial perfusion, but impaired regional
      perfusion of the kidneys and the pancreas.

PMID- 15504198
TI  - Treatment of a transdiaphragmatic fistula with an endobronchial-blocking
      catheter.
AB  - We report a case of a bronchosubphrenic fistula in a 59-year-old female following
      hemicolectomy complicated by fecal peritonitis. The patient needed intubation and
      positive-pressure ventilation, which caused a massive air leak. The fistula was
      treated using an endobronchial blocking catheter in combination with antibiotic
      treatment and drainage.

PMID- 15504199
TI  - Intravenous anaesthesia combined with peribulbar block in a child with suspected
      Duchenne muscular dystrophy.

PMID- 15504200
TI  - Continuous popliteal sciatic nerve block. How to be sure the catheter works?

PMID- 15504201
TI  - Pulmonary soiling by pus after one-lung ventilation with a Univent tube.

PMID- 15504204
TI  - Introduction to the guidelines.

PMID- 15504205
TI  - Screening of donor and recipient prior to solid organ transplantation.

PMID- 15504206
TI  - Multiply antibiotic-resistant gram-negative bacteria.

PMID- 15504207
TI  - Legionella.

PMID- 15504208
TI  - Clostridium difficile.

PMID- 15504209
TI  - Multiply resistant Gram-positive bacteria.

PMID- 15504210
TI  - Mycobacterium tuberculosis.

PMID- 15504211
TI  - Nontuberculous mycobacteria.

PMID- 15504212
TI  - Nocardia infections.

PMID- 15504213
TI  - Cytomegalovirus.

PMID- 15504214
TI  - Epstein-Barr virus and lymphoproliferative disorders after transplantation.

PMID- 15504215
TI  - Other herpesviruses: HHV-6, HHV-7, HHV-8, HSV-1 and -2, VZV.

PMID- 15504218
TI  - Viral hepatitis guidelines in hemodialysis and transplantation.

PMID- 15504219
TI  - Solid organ transplantation in the HIV-infected patient.

PMID- 15504220
TI  - BK virus.

PMID- 15504221
TI  - Human parvovirus B19.

PMID- 15504222
TI  - Human papillomavirus infection.

PMID- 15504223
TI  - Adenovirus.

PMID- 15504224
TI  - Community-acquired respiratory viruses.

PMID- 15504225
TI  - Fungal infections.

PMID- 15504226
TI  - Pneumocystis jiroveci (formerly Pneumocystis carinii).

PMID- 15504227
TI  - Parasitic infections.

PMID- 15504228
TI  - Strategies for safe living following solid organ transplantation.

PMID- 15504229
TI  - Guidelines for vaccination of solid organ transplant candidates and recipients.

PMID- 15504230
TI  - Immunosuppressive drug interactions with anti-infective agents.

PMID- 15504231
TI  - Second edition of 'The Bethesda System for reporting cervical cytology' - atlas,
      website, and Bethesda interobserver reproducibility project.
AB  - A joint task force of the American Society of Cytopathology (ASC) and the
      National Cancer Institute (NCI) recently completed a 2-year effort to revise the
      Bethesda System "blue book" atlas and develop a complementary web-based
      collection of cervical cytology images. The web-based collection of images is
      housed on the ASC website, which went live on November 5th, 2003; it can be
      directly accessed at http://www.cytopathology.org/NIH/.

PMID- 15504232
TI  - A touchdown nucleic acid amplification protocol as an alternative to culture
      backup for immunofluorescence in the routine diagnosis of acute viral respiratory
      tract infections.
AB  - BACKGROUND: Immunofluorescence and virus culture are the main methods used to
      diagnose acute respiratory virus infections. Diagnosing these infections using
      nucleic acid amplification presents technical challenges, one of which is
      facilitating the different optimal annealing temperatures needed for each virus.
      To overcome this problem we developed a diagnostic molecular strip which combined
      a generic nested touchdown protocol with in-house primer master-mixes that could
      recognise 12 common respiratory viruses. RESULTS: Over an 18 month period a total
      of 222 specimens were tested by both immunofluorescence and the molecular strip.
      The specimens came from 103 males (median age 3.5 y), 80 females (median age 9 y)
      and 5 quality assurance scheme specimens. Viruses were recovered from a number of
      specimen types including broncho-alveolar lavage, nasopharyngeal secretions,
      sputa, post-mortem lung tissue and combined throat and nasal swabs. Viral
      detection by IF was poor in sputa and respiratory swabs. A total of 99 viruses
      were detected in the study from 79 patients and 4 quality control specimens: 31
      by immunofluorescence and 99 using the molecular strip. The strip consistently
      out-performed immunofluorescence with no loss of diagnostic specificity.
      CONCLUSIONS: The touchdown protocol with pre-dispensed primer master-mixes was
      suitable for replacing virus culture for the diagnosis of respiratory viruses
      which were negative by immunofluorescence. Results by immunofluorescence were
      available after an average of 4-12 hours while molecular strip results were
      available within 24 hours, considerably faster than viral culture. The combined
      strip and touchdown protocol proved to be a convenient and reliable method of
      testing for multiple viruses in a routine setting.

PMID- 15504233
TI  - Psychological trauma and evidence for enhanced vulnerability for posttraumatic
      stress disorder through previous trauma among West Nile refugees.
AB  - BACKGROUND: Political instability and the civil war in Southern Sudan have
      resulted in numerous atrocities, mass violence, and forced migration for vast
      parts of the civilian population in the West Nile region. High exposure to
      traumatic experiences has been particularly prominent in the Ugandan and Sudanese
      of the West Nile Region, representing an indication of the psychological strain
      posed by years of armed conflict. METHODS: In this study the impact of traumatic
      events on the prevalence and severity of posttraumatic stress disorder (PTSD) in
      a random sample of 3.339 Ugandan nationals, Sudanese nationals, and Sudanese
      refugees (1.831 households) of the West Nile region is assessed. RESULTS: Results
      show a positive correlation between the number of traumatic events and the number
      of endorsed PTSD symptoms. Of the 58 respondents who experienced the greatest
      number of traumatizing experiences, all reported symptoms which met the DSM-IV
      criteria for PTSD. CONCLUSIONS: There is a clear dose-effect relationship between
      traumatic exposure and PTSD in the studied populations with high levels of
      traumatic events. In this context, it is probable that any individual could
      develop PTSD regardless of other risk-factors once the trauma load reaches a
      certain threshold.

PMID- 15504234
TI  - Gapped alignment of protein sequence motifs through Monte Carlo optimization of a
      hidden Markov model.
AB  - BACKGROUND: Certain protein families are highly conserved across distantly
      related organisms and belong to large and functionally diverse superfamilies. The
      patterns of conservation present in these protein sequences presumably are due to
      selective constraints maintaining important but unknown structural mechanisms
      with some constraints specific to each family and others shared by a larger
      subset or by the entire superfamily. To exploit these patterns as a source of
      functional information, we recently devised a statistically based approach called
      contrast hierarchical alignment and interaction network (CHAIN) analysis, which
      infers the strengths of various categories of selective constraints from co
      conserved patterns in a multiple alignment. The power of this approach strongly
      depends on the quality of the multiple alignments, which thus motivated
      development of theoretical concepts and strategies to improve alignment of
      conserved motifs within large sets of distantly related sequences. RESULTS: Here
      we describe a hidden Markov model (HMM), an algebraic system, and Markov chain
      Monte Carlo (MCMC) sampling strategies for alignment of multiple sequence motifs.
      The MCMC sampling strategies are useful both for alignment optimization and for
      adjusting position specific background amino acid frequencies for alignment
      uncertainties. Associated statistical formulations provide an objective measure
      of alignment quality as well as automatic gap penalty optimization. Improved
      alignments obtained in this way are compared with PSI-BLAST based alignments
      within the context of CHAIN analysis of three protein families: Gialpha subunits,
      prolyl oligopeptidases, and transitional endoplasmic reticulum (p97) AAA+
      ATPases. CONCLUSION: While not entirely replacing PSI-BLAST based alignments,
      which likewise may be optimized for CHAIN analysis using this approach, these
      motif-based methods often more accurately align very distantly related sequences
      and thus can provide a better measure of selective constraints. In some
      instances, these new approaches also provide a better understanding of family
      specific constraints, as we illustrate for p97 ATPases. Programs implementing
      these procedures and supplementary information are available from the authors.

PMID- 15504236
TI  - Family doctors' involvement with families in Estonia.
AB  - BACKGROUND: Family doctors should care for individuals in the context of their
      family. Family has a powerful influence on health and illness and family
      interventions have been shown to improve health outcomes for a variety of health
      problems. The aim of the study was to investigate the Estonian family doctors'
      (FD) attitudes to the patients' family-related issues in their work: to explore
      the degree of FDs involvement in family matters, their preparedness for
      management of family-related issues and their self-assessment of the ability to
      manage different family-related problems. METHODS: A random sample (n = 236) of
      all FDs in Estonia was investigated using a postal questionnaire. Altogether 151
      FDs responded to the questionnaire (response rate 64%), while five of them were
      excluded as they did not actually work as FDs. RESULTS: Of the respondents, 90%
      thought that in managing the health problems of patients FDs should communicate
      and cooperate with family members. Although most of the family doctors agreed
      that modifying of the health damaging risk factors (smoking, alcohol and drug
      abuse) of their patients and families is their task, one third of them felt that
      dealing with these problems is ineffective, or perceived themselves as poorly
      prepared or having too little time for such activities. Of the respondents, 58%
      (n = 83) were of the opinion that they could modify also relationship problems.
      CONCLUSIONS: Estonian family doctors are favourably disposed to involvement in
      family-related problems, however, they need some additional training, especially
      in the field of relationship management.

PMID- 15504235
TI  - Multimodal pressure-flow method to assess dynamics of cerebral autoregulation in
      stroke and hypertension.
AB  - BACKGROUND: This study evaluated the effects of stroke on regulation of cerebral
      blood flow in response to fluctuations in systemic blood pressure (BP). The
      autoregulatory dynamics are difficult to assess because of the nonstationarity
      and nonlinearity of the component signals. METHODS: We studied 15 normotensive,
      20 hypertensive and 15 minor stroke subjects (48.0 +/- 1.3 years). BP and blood
      flow velocities (BFV) from middle cerebral arteries (MCA) were measured during
      the Valsalva maneuver (VM) using transcranial Doppler ultrasound. RESULTS: A new
      technique, multimodal pressure-flow analysis (MMPF), was implemented to analyze
      these short, nonstationary signals. MMPF analysis decomposes complex BP and BFV
      signals into multiple empirical modes, representing their instantaneous frequency
      amplitude modulation. The empirical mode corresponding to the VM BP profile was
      used to construct the continuous phase diagram and to identify the minimum and
      maximum values from the residual BP (BPR) and BFV (BFVR) signals. The BP-BFV
      phase shift was calculated as the difference between the phase corresponding to
      the BPR and BFVR minimum (maximum) values. BP-BFV phase shifts were significantly
      different between groups. In the normotensive group, the BFVR minimum and maximum
      preceded the BPR minimum and maximum, respectively, leading to large positive
      values of BP-BFV shifts. CONCLUSION: In the stroke and hypertensive groups, the
      resulting BP-BFV phase shift was significantly smaller compared to the
      normotensive group. A standard autoregulation index did not differentiate the
      groups. The MMPF method enables evaluation of autoregulatory dynamics based on
      instantaneous BP-BFV phase analysis. Regulation of BP-BFV dynamics is altered
      with hypertension and after stroke, rendering blood flow dependent on blood
      pressure.

PMID- 15504237
TI  - Microarray and comparative genomics-based identification of genes and gene
      regulatory regions of the mouse immune system.
AB  - BACKGROUND: In this study we have built and mined a gene expression database
      composed of 65 diverse mouse tissues for genes preferentially expressed in immune
      tissues and cell types. Using expression pattern criteria, we identified 360
      genes with preferential expression in thymus, spleen, peripheral blood
      mononuclear cells, lymph nodes (unstimulated or stimulated), or in vitro
      activated T-cells. RESULTS: Gene clusters, formed based on similarity of
      expression-pattern across either all tissues or the immune tissues only, had
      highly significant associations both with immunological processes such as
      chemokine-mediated response, antigen processing, receptor-related signal
      transduction, and transcriptional regulation, and also with more general
      processes such as replication and cell cycle control. Within-cluster gene
      correlations implicated known associations of known genes, as well as immune
      process-related roles for poorly described genes. To characterize regulatory
      mechanisms and cis-elements of genes with similar patterns of expression, we used
      a new version of a comparative genomics-based cis-element analysis tool to
      identify clusters of cis-elements with compositional similarity among multiple
      genes. Several clusters contained genes that shared 5-6 cis-elements that
      included ETS and zinc-finger binding sites. cis-Elements AP2 EGRF ETSF MAZF SP1F
      ZF5F and AREB ETSF MZF1 PAX5 STAT were shared in a thymus-expressed set; AP4R
      E2FF EBOX ETSF MAZF SP1F ZF5F and CREB E2FF MAZF PCAT SP1F STAT cis-clusters
      occurred in activated T-cells; CEBP CREB NFKB SORY and GATA NKXH OCT1 RBIT
      occurred in stimulated lymph nodes. CONCLUSION: This study demonstrates a series
      of analytic approaches that have allowed the implication of genes and regulatory
      elements that participate in the differentiation, maintenance, and function of
      the immune system. Polymorphism or mutation of these could adversely impact
      immune system functions.

PMID- 15504238
TI  - A computational approach for ordering signal transduction pathway components from
      genomics and proteomics Data.
AB  - BACKGROUND: Signal transduction is one of the most important biological processes
      by which cells convert an external signal into a response. Novel computational
      approaches to mapping proteins onto signaling pathways are needed to fully take
      advantage of the rapid accumulation of genomic and proteomics information.
      However, despite their importance, research on signaling pathways reconstruction
      utilizing large-scale genomics and proteomics information has been limited.
      RESULTS: We have developed an approach for predicting the order of signaling
      pathway components, assuming all the components on the pathways are known. Our
      method is built on a score function that integrates protein-protein interaction
      data and microarray gene expression data. Compared to the individual datasets,
      either protein interactions or gene transcript abundance measurements, the
      integrated approach leads to better identification of the order of the pathway
      components. CONCLUSIONS: As demonstrated in our study on the yeast MAPK signaling
      pathways, the integration analysis of high-throughput genomics and proteomics
      data can be a powerful means to infer the order of pathway components, enabling
      the transformation from molecular data into knowledge of cellular mechanisms.

PMID- 15504239
TI  - Combining gene expression data from different generations of oligonucleotide
      arrays.
AB  - BACKGROUND: One of the important challenges in microarray analysis is to take
      full advantage of previously accumulated data, both from one's own laboratory and
      from public repositories. Through a comparative analysis on a variety of
      datasets, a more comprehensive view of the underlying mechanism or structure can
      be obtained. However, as we discover in this work, continual changes in genomic
      sequence annotations and probe design criteria make it difficult to compare gene
      expression data even from different generations of the same microarray platform.
      RESULTS: We first describe the extent of discordance between the results derived
      from two generations of Affymetrix oligonucleotide arrays, as revealed in cluster
      analysis and in identification of differentially expressed genes. We then propose
      a method for increasing comparability. The dataset we use consists of a set of 14
      human muscle biopsy samples from patients with inflammatory myopathies that were
      hybridized on both HG-U95Av2 and HG-U133A human arrays. We find that the use of
      the probe set matching table for comparative analysis provided by Affymetrix
      produces better results than matching by UniGene or LocusLink identifiers but
      still remains inadequate. Rescaling of expression values for each gene across
      samples and data filtering by expression values enhance comparability but only
      for few specific analyses. As a generic method for improving comparability, we
      select a subset of probes with overlapping sequence segments in the two array
      types and recalculate expression values based only on the selected probes. We
      show that this filtering of probes significantly improves the comparability while
      retaining a sufficient number of probe sets for further analysis. CONCLUSIONS:
      Compatibility between high-density oligonucleotide arrays is significantly
      affected by probe-level sequence information. With a careful filtering of the
      probes based on their sequence overlaps, data from different generations of
      microarrays can be combined more effectively.

PMID- 15504240
TI  - Reuse of imputed data in microarray analysis increases imputation efficiency.
AB  - BACKGROUND: The imputation of missing values is necessary for the efficient use
      of DNA microarray data, because many clustering algorithms and some statistical
      analysis require a complete data set. A few imputation methods for DNA microarray
      data have been introduced, but the efficiency of the methods was low and the
      validity of imputed values in these methods had not been fully checked. RESULTS:
      We developed a new cluster-based imputation method called sequential K-nearest
      neighbor (SKNN) method. This imputes the missing values sequentially from the
      gene having least missing values, and uses the imputed values for the later
      imputation. Although it uses the imputed values, the efficiency of this new
      method is greatly improved in its accuracy and computational complexity over the
      conventional KNN-based method and other methods based on maximum likelihood
      estimation. The performance of SKNN was in particular higher than other
      imputation methods for the data with high missing rates and large number of
      experiments. Application of Expectation Maximization (EM) to the SKNN method
      improved the accuracy, but increased computational time proportional to the
      number of iterations. The Multiple Imputation (MI) method, which is well known
      but not applied previously to microarray data, showed a similarly high accuracy
      as the SKNN method, with slightly higher dependency on the types of data sets.
      CONCLUSIONS: Sequential reuse of imputed data in KNN-based imputation greatly
      increases the efficiency of imputation. The SKNN method should be practically
      useful to save the data of some microarray experiments which have high amounts of
      missing entries. The SKNN method generates reliable imputed values which can be
      used for further cluster-based analysis of microarray data.

PMID- 15504241
TI  - Implications for domain fusion protein-protein interactions based on structural
      information.
AB  - BACKGROUND: Several in silico methods exist that were developed to predict
      protein interactions from the copious amount of genomic and proteomic data. One
      of these methods is Domain Fusion, which has proven to be effective in predicting
      functional links between proteins. RESULTS: Analyzing the structures of multi
      domain single-chain peptides, we found that domain pairs located less than 30
      residues apart on a chain are almost certain to share a physical interface. The
      majority of these interactions are also conserved across separate chains. We make
      use of this observation to improve domain fusion based protein interaction
      predictions, and demonstrate this by implementing it on a set of Saccharomyces
      cerevisiae proteins. CONCLUSION: We show that existing structural data supports
      the domain fusion hypothesis. Empirical information from structural data also
      enables us to refine and assess domain fusion based protein interaction
      predictions. These interactions can then be integrated with downstream
      biochemical and genetic assays to generate more reliable protein interaction data
      sets.

PMID- 15504242
TI  - What are the reasons for negative phase III trials of molecular-target-based
      drugs?
AB  - The results of molecular-biological studies of cancer are changing the way we
      diagnose and treat cancer. Target-based drug discovery selects agents for
      development based on their mechanisms of action. The interaction between target
      based drugs and their targets can be described by classical drug-receptor theory.
      Clinical trials have demonstrated that some effective target-based drugs induce
      apoptosis, even though they are considered to be cytostatic. Numerous phase III
      trials of target-based drugs have been conducted. Although some have yielded
      strongly positive results, the majority of the results have been negative. This
      article seeks to clarify the value of molecular-target-based therapy and to
      discuss the reasons for negative results in phase III trials. The importance of
      proof-of-principle studies is stressed throughout preclinical and clinical trials
      of molecular-target-based drugs.

PMID- 15504243
TI  - TRAIL and its receptors as targets for cancer therapy.
AB  - Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member
      of the TNF family of cytokines, which can induce apoptotic cell death in a
      variety of tumor cells by engaging the death receptors DR4 and DR5, while sparing
      most normal cells. Preclinical studies in mice and non-human primates have shown
      the potential utility of recombinant soluble TRAIL and agonistic anti-DR5 or DR4
      antibodies for cancer therapy. Moreover, we have recently revealed a vital role
      for endogenously expressed TRAIL in immunosurveillance of developing and
      metastatic tumors. In this review, we summarize recent knowledge about TRAIL and
      its receptors as promising targets for cancer therapy.

PMID- 15504244
TI  - Identification of human tumor antigens and its implications for diagnosis and
      treatment of cancer.
AB  - Human tumor antigens recognized by T cells have been identified by means of
      various molecular biological and immunological methods, including cDNA expression
      cloning with patients' T cells and antibodies, cDNA subtraction using RDA and PCR
      differential display, systematic gene analysis such as DNA sequencing, CGH, DNA
      chip/microarray and SAGE, in vitro T cell induction and immunization of HLA
      transgenic mice. The identification of human tumor antigens has led to a better
      understanding of the nature of tumor antigens, anti-tumor immune responses in
      patients before and after immunotherapy, and tumor escape mechanisms. The
      information obtained from these researches has enabled us to develop and improve
      immunotherapy by attempting to overcome the identified problems, including
      intrinsically low immunogenicity of tumor antigens and several escape mechanisms,
      such as regulatory T cell induction. The existence of immunogenic unique antigens
      derived from genetic alterations in tumor cells, and the varied immunogenicity of
      shared tumor antigens among patients due to differing expression in tumor cells
      and immunoreactivity of patients, indicates that individualized immunotherapy
      should ideally be performed. The identified antigens will also be useful for
      development of diagnostic methods and molecular targeting therapy for cancer.

PMID- 15504245
TI  - Histological and immunohistochemical observations of mucin-depleted foci (MDF)
      stained with Alcian blue, in rat colon carcinogenesis induced with 1,2
      dimethylhydrazine dihydrochloride.
AB  - The usefulness of mucin-depleted foci (MDF), which have recently been proposed as
      a new preneoplastic biomarker in rat colon carcinogenesis, was histologically
      investigated in rat colonic tissues treated with 1,2-dimethylhydrazine
      dihydrochloride (DMH). The relationship among aberrant crypt foci (ACF), MDF and
      beta-catenin accumulated crypts (BCAC) was examined by comparing the
      corresponding computer-captured images. Twelve male F344 rats were given DMH s.c.
      at a dose of 40 mg/kg body weight, once a week for 2 weeks, and randomly divided
      into two groups. Rats in group 1 were given normal drinking water, while those in
      group 2 were given drinking water containing indomethacin (IND) at 16 ppm for 6
      weeks. All animals were sacrificed 8 weeks after the first DMH treatment. The
      resected colons were fixed in 10% formalin, and stained with Alcian blue for
      observation of ACF and MDF. Histological and immunohistochemical analysis
      revealed that the numbers of ACF, MDF and overlapping lesions in group 2 (treated
      with IND) were significantly decreased, compared with those in group 1. The
      number of BCAC in group 2 was also significantly lower than that in group 1. The
      reduction (61.5%) of MDF by IND was much greater than that (29.3%) of ACF.
      Analyses of the computer-captured images indicated that MDF had more frequent
      dysplastic changes and overexpression of beta-catenin than did ACF. MDF having
      over 4 crypts or MDF with the appearance of ACF corresponded well to BCAC. These
      results suggest that MDF may be useful as an early biomarker in colon
      carcinogenesis.

PMID- 15504246
TI  - Cloning of Mongolian gerbil cDNAs encoding inflammatory proteins, and their
      expression in glandular stomach during H. pylori infection.
AB  - Mongolian gerbils are considered to be a good animal model for understanding the
      development of Helicobacter pylori-associated diseases. However, limitations
      regarding the genetic information available for this animal species hamper the
      elucidation of underlying mechanisms. Thus, we have focused on identifying the
      nucleotide sequences of cDNAs encoding Mongolian gerbil inflammatory proteins,
      such as interleukin-1 (IL-1beta), tumor necrosis factor alpha (TNF-alpha),
      cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Furthermore,
      we examined the mRNA expression of these genes in the glandular stomach by RT-PCR
      at 1-8 weeks after H. pylori infection. The deduced amino acid homologies to
      mouse, rat and human proteins were 86.2%, 83.6% and 67.8% for IL-1beta, 87.2%,
      85.1% and 78.4% for TNF-alpha , 91.9%, 90.2% and 84.8% for COX-2 and 90.8%, 89.1%
      and 80.1% for iNOS, respectively. The average stomach weight of Mongolian gerbils
      inoculated with H. pylori was increased in a time-dependent manner at 1, 2, 4 and
      8 weeks after inoculation. In the pyloric region, mRNA expression levels of IL
      1beta, TNF-alpha and iNOS were increased in H. pylori-infected animals at the 2
      weeks time point, while in the fundic region, expression levels of IL-1beta, TNF
      alpha and iNOS were elevated at 4 and 8 weeks. The COX-2 expression level in the
      fundic region was clearly elevated in infected animals compared with control
      animals at 4 and 8 weeks, but in the pyloric region, expression levels were
      similar in both infected and control animals. Thus, our results indicate that
      oxidative stress occurs from an early stage of H. pylori infection in the
      glandular stomach of Mongolian gerbils.

PMID- 15504247
TI  - Activation of c-Met (hepatocyte growth factor receptor) in human gastric cancer
      tissue.
AB  - c-Met is a high-affinity receptor for hepatocyte growth factor (HGF) and plays a
      crucial role in embryonic development, as well as in the process of tissue
      repair. Overexpression and amplification of c-Met are often observed in various
      cancer tissues, especially in gastric carcinoma. It has, however, been unclear
      whether the overexpression leads to activation of the c-Met receptor. To address
      this point, we prepared an antibody (anti-phospho-Met) which specifically
      recognizes c-Met that is phosphorylated at Y1235, a major phosphorylation site of
      c-Met. Normal as well as cancerous gastric tissue was positive for anti-total-Met
      staining, whereas only cancerous tissue was strongly positive for anti-phospho
      Met staining; cells near the basal layer were moderately positive, and the
      proliferative zone in normal tissue was only weakly positive. Among cancerous
      tissues from seven patients examined in the present study, those from six
      patients were strongly positive for phospho-Met staining. These results indicate
      that c-Met is actually activated in gastric carcinoma tissue, and may trigger
      proliferation/anti-apoptotic signals.

PMID- 15504248
TI  - Comparison of genetic aberrations in CD10+ diffused large B-cell lymphoma and
      follicular lymphoma by comparative genomic hybridization and tissue-fluorescence
      in situ hybridization.
AB  - CD10 is one of the hallmarks of germinal center B-cells where follicular
      lymphomas (FL) originate. It has not been clearly established, however, whether
      CD10(+) diffuse B-cell lymphomas (DLBCL) are genetically similar to FL. We
      therefore examined 19 CD10(+) DLBCL and 40 FL by means of comparative genomic
      hybridization (CGH) and tissue-fluorescence in situ hybridization (T-FISH).
      Chromosomal imbalance was more frequently detected in CD10(+) DLBCLs (19/19) than
      in FLs (24/40). Significant differences were found in eight frequently imbalanced
      regions, namely those with gains of chromosomes 7q and 12 and those with losses
      of chromosomes 1p, 4p, 6q, 15q, 16p and 17. Amplification of the 3q region where
      BCL6 is located is reported to occur frequently in DLBCL, but it was only found
      in one of the 19 CD10(+) DLBCL cases we examined. The involvement of t(14;18) in
      CD10(+)+ DLBCL (31%) and in FL (73%) was significantly different (P = 0.0064).
      The CGH pattern of CD10(+) DLBCL with t(14;18) was also different from that of FL
      with t(14;18). Taken together, our results indicate that CD10(+) DLBCL
      constitutes a unique subtype entity with genetic characteristics significantly
      different from those of FL and DLBCL.

PMID- 15504249
TI  - Identification of a mouse cytoskeleton-associated protein, CKAP2, with
      microtubule-stabilizing properties.
AB  - Microtubule dynamics is an important factor in cell proliferation and one of the
      main targets of cancer chemotherapy. Since microtubule-associated proteins (MAPs)
      are known to influence microtubule stability, study of MAPs may contribute both
      to knowledge of cancer cell biology and to the production of new anti-cancer
      drugs. In this study, we identified a new mouse gene which is a homolog of human
      cytoskeleton-associated protein, CKAP2 gene, by differential display analysis.
      The level of expression of mouse CKAP2 (mCKAP2) was significantly higher in
      NIH3T3 cells expressing RET with a multiple endocrine neoplasia (MEN) 2A or MEN2B
      mutation than in parental NIH3T3 cells. Immunocytochemical analysis showed that
      mCKAP2 protein is localized in cytoplasm with a fibrillar appearance, and is co
      localized with microtubules throughout the cell cycle. Furthermore,
      overexpression of mCKAP2 in cells appeared to stabilize microtubules against
      treatment with nocodazole, a microtubule-depolymerizing agent. In addition,
      levels of human CKAP2 were increased in some human tumor cell lines examined.
      These findings suggest that CKAP2 is a new MAP with microtubule-stabilizing
      properties and may represent a new molecular target for cancer chemotherapy.

PMID- 15504250
TI  - Overexpression of the Wilms' tumor gene W T1 in primary astrocytic tumors.
AB  - Expression of the Wilms' tumor gene W T1 in primary astrocytic tumors was
      examined using a quantitative real-time reverse transcriptase-polymerase chain
      reaction (RT-PCR) or immunohistochemistry. Real-time RT-PCR showed that W T1 mRNA
      was expressed at various levels in all of the 25 astrocytic tumors examined.
      Immunohistochemical analysis showed that W T1 protein was expressed in 5 of 6 low
      grade astrocytic tumors (grade I-II) and all of 18 high-grade ones (grade III
      IV), and that expression levels of W T1 protein in high-grade tumors were
      significantly higher than those in low-grade ones. W T1 protein was not detected
      in the normal glial cells contained in the tumor specimens. Furthermore,
      treatment with W T1 antisense oligomers specifically inhibited growth of
      glioblastoma cell lines, U87-MG, A172, and T-98G. These results may indicate that
      the W T1 gene plays an important role in tumorigenesis of primary astrocytic
      tumors.

PMID- 15504251
TI  - Distinct pattern of gene expression in pyothorax-associated lymphoma (PAL), a
      lymphoma developing in long-standing inflammation.
AB  - Pyothorax-associated lymphoma (PAL) is a unique lymphoma developing in the
      pleural cavity after long-standing pyothorax. They are diffuse large B-cell
      lymphomas (DLBCLs), frequently with immunoblastic morphology, and show a strong
      association with Epstein-Barr virus (EBV) infection. In this study, cDNA
      microarray analysis was performed in six cases with PAL and 12 with nodal DLBCL.
      Among 5516 informative genes, 348 displayed more than 2-fold difference (higher
      or lower) of expression level between PAL and nodal DLBCL (P < 0.001). These
      genes are known to be involved in apoptosis, interferon response, and signal
      transduction. One of the most differentially expressed genes, IFI27 (interferon
      alpha-inducible protein 27) was subjected to quantitative RT-PCR analysis, and
      increased expression of IFI27 was confirmed. Overexpression of IFI27 was also
      found in cell lines derived from PAL, but not in other lymphoid cell lines. This
      study shows that PAL is a distinctive subtype of DLBCL not only in its clinical
      presentation, but also in its molecular profile.

PMID- 15504252
TI  - Novel biomarker of HTLV-1-associated disease: specific appearance of antibody
      recognizing the receptor-binding site on HTLV-1 envelope protein.
AB  - We previously showed that 71-kDa heat shock cognate protein (HSC70) functions as
      a cellular receptor for gp46 protein via the gp46-197 region, corresponding to
      Asp197 to Leu216 of human T-cell lymphotropic virus type 1 (HTLV-1), leading to
      cell-to-cell transmission of HTLV-1. We found that HSC70 protein was contained in
      goat serum and casein used as blocking agents in the usual ELISA method. Here, it
      was demonstrated that HSC70 contamination in the blocking agents causes a false
      negative result in the detection of anti-gp46-197 antibody in serum samples from
      HTLV-1-infected individuals. By using ELISA without the blocking agents, we
      detected antibodies recognizing the HSC70-binding site of gp46, and the anti-gp46
      197 antibody specifically appeared in sera from patients with HTLV-1-associated
      diseases. The frequency of serum anti-gp46-197 antibody-positive individuals was
      98% and 100% among ATLL and HAM/TSP patients, respectively, but only 6% among
      asymptomatic HTLV-1-infected carriers (ACs). The antibody titer in ATLL and
      HAM/TSP patients was higher than that in ACs (P < 0.002 for ATLL; P < 0.0001 for
      HAM/TSP). These findings suggest that appearance of the anti-gp46-197 antibody is
      a predictive marker for the onset of HTLV-1-associated disease.

PMID- 15504253
TI  - Sensitization of human glioblastomas to tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL) by NF-kappaB inhibitors.
AB  - Glioblastoma is the most malignant form of primary brain tumor in adults, with no
      effective therapy and a low survival rate. TRAIL is a member of the TNF family,
      which selectively induces apoptosis in certain neoplastic cells, but not normal
      cells. In this study, we investigated the sensitivity of 7 human glioblastoma
      cell lines to TRAIL and the expression in them of TRAIL receptors. TRAIL
      exhibited significant cytotoxicity in 5 of 7 glioma cell lines. These
      glioblastoma cell lines expressed TRAIL-R2, but not TRAIL-R1, R3, or R4. However,
      no correlation was observed between the TRAIL sensitivity and the TRAIL-R2
      expression level, suggesting that there is an additional determinant of TRAIL
      sensitivity. Treatments with NF-kappaB inhibitors, such as LLnL, MG132, and SN50,
      significantly increased the sensitivity of glioma cells to TRAIL. These results
      suggested that activation of NF-kappaB is a protective mechanism against TRAIL
      induced cell death in some glioma cells, and thus NF-kappaB inhibitors may be
      useful to improve the clinical treatment of glioblastoma with TRAIL.

PMID- 15504254
TI  - Enhanced antitumor activity of ultrasonic irradiation in the presence of new
      quinolone antibiotics in vitro.
AB  - To determine if there is any synergistic antitumor effect of ultrasound (US) in
      the presence of new quinolone (NQ) antibiotics, 0.2 mM solutions of lomefloxacin
      hydrochloride (LFLX), sparfloxacin (SPFX), ciprofloxacin hydrochloride (CPFX),
      and gatifloxacin hydrate (GFLX) were tested as sonodynamic agents against sarcoma
      180 cells in vitro. After US irradiation at 2 W/cm(2) for 30 and 60 s, the
      survival rates of tumor cells in the presence of NQ antibiotics were
      significantly lower than those in their absence (P < 0.001). In May-Giemsa
      smears, most of the tumor cells remained intact in the control group. However, in
      the 0.2 mM SPFX group, the tumor cells were mostly fragmented. The synergistic
      antitumor effect of SPFX was dose-dependent. Furthermore, when D-mannitol was
      used with SPFX, the survival rate of tumor cells after irradiation was comparable
      with that when SPFX alone was applied, but when L-histidine was used
      concurrently, the survival rate of tumor cells was significantly higher than that
      when SPFX alone was applied. These findings suggest that NQ antibiotics would
      exhibit useful antitumor activity under US irradiation, and that generation of
      singlet oxygen is involved in the process of cell damage.

PMID- 15504255
TI  - Current epidemiology of Pneumocystis pneumonia.
AB  - Pneumocystis pneumonia (PCP) has historically been one of the leading causes of
      disease among persons with AIDS. The introduction of highly active antiretroviral
      therapy in industrialized nations has brought about dramatic declines in the
      incidence of AIDS-associated complications, including PCP. In the adult
      population, the incidence of PCP has significantly decreased, but it remains
      among the most common AIDS-defining infections. Similar declines have been
      documented in the pediatric population. In much of the developing world, PCP
      remains a significant health problem, although its incidence among adults in sub
      Saharan Africa has been debated. This review discusses the epidemiology of PCP
      during the current era of the AIDS epidemic. Although fewer cases of PCP occur in
      industrialized countries, increasing drug-resistant HIV infections, possible drug
      resistant PCP, and the tremendous number of AIDS cases in developing countries
      make this disease of continued public health importance.

PMID- 15504256
TI  - Dihydropteroate synthase gene mutations in Pneumocystis and sulfa resistance.
AB  - Pneumocystis pneumonia (PCP) remains a major cause of illness and death in HIV
      infected persons. Sulfa drugs, trimethoprim-sulfamethoxazole (TMP-SMX) and
      dapsone are mainstays of PCP treatment and prophylaxis. While prophylaxis has
      reduced the incidence of PCP, its use has raised concerns about development of
      resistant organisms. The inability to culture human Pneumocystis, Pneumocystis
      jirovecii, in a standardized culture system prevents routine susceptibility
      testing and detection of drug resistance. In other microorganisms, sulfa drug
      resistance has resulted from specific point mutations in the dihydropteroate
      synthase (DHPS) gene. Similar mutations have been observed in P. jirovecii.
      Studies have consistently demonstrated a significant association between the use
      of sulfa drugs for PCP prophylaxis and DHPS gene mutations. Whether these
      mutations confer resistance to TMP-SMX or dapsone plus trimethoprim for PCP
      treatment remains unclear. We review studies of DHPS mutations in P. jirovecii
      and summarize the evidence for resistance to sulfamethoxazole and dapsone.

PMID- 15504257
TI  - Strain typing methods and molecular epidemiology of Pneumocystis pneumonia.
AB  - Pneumocystis pneumonia (PCP) caused by the opportunistic fungal agent
      Pneumocystis jirovecii (formerly P. carinii) continues to cause illness and death
      in HIV-infected patients. In the absence of a culture system to isolate and
      maintain live organisms, efforts to type and characterize the organism have
      relied on polymerase chain reaction-based approaches. Studies using these methods
      have improved understanding of PCP epidemiology, shedding light on sources of
      infection, transmission patterns, and potential emergence of antimicrobial
      resistance. One concern, however, is the lack of guidance regarding the
      appropriateness of different methods and standardization of these methods, which
      would facilitate comparing results reported by different laboratories.

PMID- 15504258
TI  - West Nile virus economic impact, Louisiana, 2002.
AB  - West Nile virus (WNV) is transmitted by mosquitoes and can cause illness in
      humans ranging from mild fever to encephalitis. In 2002, a total of 4,156 WNV
      cases were reported in the United States; 329 were in Louisiana. To estimate the
      economic impact of the 2002 WNV epidemic in Louisiana, we collected data from
      hospitals, a patient questionnaire, and public offices. Hospital charges were
      converted to economic costs by using Medicare cost-to-charge ratios. The
      estimated cost of the Louisiana epidemic was US 20.1 million dollars from June
      2002 to February 2003, including a US 10.9 million dollars cost of illness (US
      4.4 million dollars medical and US 6.5 million dollars nonmedical costs) and a US
      9.2 million dollars cost of public health response. These data indicate a
      substantial short-term cost of the WNV disease epidemic in Louisiana.

PMID- 15504259
TI  - Virus-specific RNA and antibody from convalescent-phase SARS patients discharged
      from hospital.
AB  - Severe acute respiratory syndrome (SARS) is caused by a novel coronavirus (SARS
      CoV). In a longitudinal cross-sectional study, we determined the prevalence of
      virus in bodily excretions and time of seroconversion in discharged patients with
      SARS. Conjunctival, throat, stool, and urine specimens were collected weekly from
      64 patients and tested for SARS-CoV RNA by real-time polymerase chain reaction;
      serum samples were collected weekly and tested for SARS-CoV antibody with
      indirect enzyme immunoassay and immunofluorescence assay. In total, 126
      conjunctival, 124 throat swab, 116 stool, and 124 urine specimens were analyzed.
      Five patients had positive stool samples, collected in weeks 5-9. Two patients
      seroconverted in weeks 7 and 8; the others were seropositive at the first serum
      sample collection. In this study, 5 (7.8%) of 64 patients continued to shed viral
      RNA in stool samples only, for up to week 8 of illness. Most seroconversions
      occurred by week 6 of illness.

PMID- 15504260
TI  - Fluoroquinolone resistance in penicillin-resistant Streptococcus pneumoniae
      clones, Spain.
AB  - Among 2,882 Streptococcus pneumoniae sent to the Spanish Reference Laboratory
      during 2002, 75 (2.6%) were ciprofloxacin-resistant. Resistance was associated
      with older patients (3.9% in adults and 7.2% in patients > or =65 years of age),
      with isolation from noninvasive sites (4.3% vs. 1.0%), and with penicillin and
      macrolide resistance. Among 14 low-level resistant (MIC 4-8 microg/mL) strains, 1
      had a fluoroquinolone efflux phenotype, and 13 showed single ParC changes. The 61
      high-level ciprofloxacin-resistant (MIC > or =16 microg/mL) strains showed either
      two or three changes at ParC, ParE, and GyrA. Resistance was acquired either by
      point mutation (70 strains) or by recombination with viridans streptococci (4
      strains) at the topoisomerase II genes. Although 36 pulsed-field gel
      electrophoresis patterns were observed, 5 international multiresistant clones
      (Spain23F-1, Spain6B-2, Spain9V-3, Spain14-5 and Sweden15A-25) accounted for 35
      (46.7%) of the ciprofloxacin-resistant strains. Continuous surveillance is needed
      to prevent the dissemination of these clones.

PMID- 15504261
TI  - Sulfa use, dihydropteroate synthase mutations, and Pneumocystis jirovecii
      pneumonia.
AB  - A systematic review was conducted to examine the associations in Pneumocystis
      jirovecii pneumonia (PCP) patients between dihydropteroate synthase (DHPS)
      mutations and sulfa or sulfone (sulfa) prophylaxis and between DHPS mutations and
      sulfa treatment outcome. Selection criteria included study populations composed
      entirely of PCP patients and mutation or treatment outcome results for all
      patients, regardless of exposure status. Based on 13 studies, the risk of
      developing DHPS mutations is higher for PCP patients receiving sulfa prophylaxis
      than for PCP patients not receiving sulfa prophylaxis (p < 0.001). Results are
      too heterogeneous (p < 0.001) to warrant a single summary effect estimate.
      Estimated effects are weaker after 1996 and stronger in studies that included
      multiple isolates per patient. Five studies examined treatment outcome. The
      effect of DHPS mutations on treatment outcome has not been well studied, and the
      few studies that have been conducted are inconsistent even as to the presence or
      absence of an association.

PMID- 15504263
TI  - Laboratory diagnosis of four recent sporadic cases of community-acquired SARS,
      Guangdong Province, China.
AB  - Four cases of severe acute respiratory syndrome (SARS) that occurred from
      December 16, 2003, to January 8, 2004, in the city of Guangzhou, Guangdong
      Province, China, were investigated. Clinical specimens collected from these
      patients were tested by provincial and national laboratories in China as well as
      members of the World Health Organization SARS Reference and Verification
      Laboratory Network in a collaborative effort to identify and confirm SARS
      associated coronavirus (SARS-CoV) infection. Although SARS-CoV was not isolated
      from any patient, specimens from three patients were positive for viral RNA by
      reverse transcription-polymerase chain reaction assay, and all patients had
      detectable rises in SARS-CoV-specific antibodies. This study shows the
      effectiveness of a collaborative, multilaboratory response to diagnose SARS.

PMID- 15504262
TI  - Molecular evidence of interhuman transmission of Pneumocystis pneumonia among
      renal transplant recipients hospitalized with HIV-infected patients.
AB  - Ten Pneumocystis jirovecii pneumonia (PCP) cases were diagnosed in renal
      transplant recipients (RTRs) during a 3-year period. Nosocomial transmission from
      HIV-positive patients with PCP was suspected because these patients shared the
      same hospital building, were not isolated, and were receiving suboptimal anti-PCP
      prophylaxis or none. P. jirovecii organisms were typed with the multitarget
      polymerase chain reaction-single-strand conformation polymorphism method. Among
      the 45 patients with PCP hospitalized during the 3-year period, 8 RTRs and 6 HIV
      infected patients may have encountered at least 1 patient with active PCP within
      the 3 months before the diagnosis of their own PCP episode. In six instances
      (five RTRs, one HIV-infected patient), the patients harbored the same P.
      jirovecii molecular type as that found in the encountered PCP patients. The data
      suggest that part of the PCP cases observed in this building, particularly those
      observed in RTRs, were related to nosocomial interhuman transmission.

PMID- 15504264
TI  - Egg quality assurance programs and egg-associated Salmonella enteritidis
      infections, United States.
AB  - A Salmonella enterica serovar Enteritidis epidemic in the United States began in
      1978, spread to much of the country in the following decade, and began declining
      in 1996. We examined correlations between annual changes in S. Enteritidis
      incidence in humans and introductions of egg quality assurance programs (EQAPs)
      in some states to reduce S. Enteritidis contamination of eggs. Before EQAPs, 62%
      of the changes in S. Enteritidis incidence were higher than the baseline for each
      state. After EQAPs, 73%-84% of the changes were below the baseline. Regression
      analysis showed that a 1% increase in the number of eggs produced under an EQAP
      was associated with a 0.14% decrease in S. Enteritidis incidence (p < 0.05).
      These data indicate that EQAPs probably played a major role in reducing S.
      Enteritidis illness in these states.

PMID- 15504265
TI  - Dengue emergence and adaptation to peridomestic mosquitoes.
AB  - Phylogenetic evidence suggests that endemic and epidemic dengue viruses (DENV),
      transmitted among humans by the anthropophilic mosquitoes Aedes aegypti and Ae.
      albopictus, emerged when ancestral, sylvatic DENV transmitted among nonhuman
      primates by sylvatic Aedes mosquitoes adapted to these peridomestic vectors. We
      tested this hypothesis by retrospectively examining evidence for adaptation of
      epidemic and endemic versus sylvatic strains of DENV-2 to Ae. albopictus and Ae.
      aegypti. First and second-generation offspring of mosquitoes from different
      geographic regions in the Americas and Southeast Asia were tested for their
      susceptibility to epidemic/endemic and sylvatic DENV-2 isolates from West Africa,
      Southeast Asia, and Oceania. Both Aedes species were highly susceptible (up to
      100% infected) to endemic/epidemic DENV-2 strains after ingesting artificial
      blood meals but significantly less susceptible (as low as 0%) to sylvatic DENV-2
      strains. Our findings support the hypothesis that adaptation to peridomestic
      mosquito vectors mediated dengue emergence from sylvatic progenitor viruses.

PMID- 15504266
TI  - Escherichia coli and community-acquired gastroenteritis, Melbourne, Australia.
AB  - As part of a study to determine the effects of water filtration on the incidence
      of community-acquired gastroenteritis in Melbourne, Australia, we examined fecal
      samples from patients with gastroenteritis and asymptomatic persons for
      diarrheagenic strains of Escherichia coli. Atypical strains of enteropathogenic
      E. coli (EPEC) were the most frequently identified pathogens of all bacterial,
      viral, and parasitic agents in patients with gastroenteritis. Moreover, atypical
      EPEC were more common in patients with gastroenteritis (89 [12.8%] of 696) than
      in asymptomatic persons (11 [2.3%] of 489, p < 0.0001). Twenty-two random
      isolates of atypical EPEC that were characterized further showed marked
      heterogeneity in terms of serotype, genetic subtype, and carriage of virulence
      associated determinants. Apart from the surface protein, intimin, no virulence
      determinant or phenotype was uniformly present in atypical EPEC strains. This
      study shows that atypical EPEC are an important cause of gastroenteritis in
      Melbourne.

PMID- 15504267
TI  - Syndromic surveillance for influenzalike illness in ambulatory care network.
AB  - Conventional disease surveillance mechanisms that rely on passive reporting may
      be too slow and insensitive to rapidly detect a large-scale infectious disease
      outbreak; the reporting time from a patient's initial symptoms to specific
      disease diagnosis takes days to weeks. To meet this need, new surveillance
      methods are being developed. Referred to as nontraditional or syndromic
      surveillance, these new systems typically rely on prediagnostic data to rapidly
      detect infectious disease outbreaks, such as those caused by bioterrorism. Using
      data from a large health maintenance organization, we discuss the development,
      implementation, and evaluation of a time-series syndromic surveillance detection
      algorithm for influenzalike illness in Minnesota.

PMID- 15504268
TI  - Disease susceptibility to ST11 complex meningococci bearing serogroup C or W135
      polysaccharide capsules, North America.
AB  - Clusters of meningococcal disease caused by a hyperinvasive lineage of Neisseria
      meningitidis, the ST11 complex, bearing a serogroup C polysaccharide capsule,
      have been prominent in Europe and North America since the early 1990s. This
      situation has led to expensive public health measures for outbreak control and,
      finally, to the introduction of a serogroup C glyconjugate vaccine into the
      primary immunization schedule in the United Kingdom and elsewhere. ST11 complex
      meningococci may also express serogroup W135 polysaccharide capsules. We
      investigated the level of population immunity to this hyperinvasive clone in
      association with the appearance of outbreaks of meningococcal disease in southern
      British Columbia. We found that most adults and almost all children were
      apparently susceptible to infection with ST11 complex meningococci bearing both C
      and W135 polysaccharide capsules, which suggests that a vaccine program directed
      against only serogroup C meningococci may be insufficient to prevent
      hyperinvasive ST11 disease.

PMID- 15504269
TI  - Genetic and transmission analysis of Helicobacter pylori strains within a family.
AB  - To look for evidence of intrafamilial infection, we isolated 107 Helicobacter
      pylori clones from biopsied specimens taken from both parents and four children.
      We compared the sequences of two housekeeping genes (hspA and glmM) from these
      clones with those of 131 unrelated strains from patients living in different
      geographic regions. Strain relationships within the family were determined by
      analyzing allelic variation at both loci and building phylogenetic trees and by
      using multilocus sequence typing. Both hspA- and glmM-based phylogenetic trees
      showed East Asian and African branches. All samples from family members showed
      natural mixed infection. Identical alleles found in some strains isolated from
      the children and parents, but not in the strains isolated from unrelated
      patients, demonstrated that strains have circulated within the family. Several
      mechanisms, such as point mutations, intragenic recombination, and introduction
      of foreign (African) alleles, were shown to enhance strain diversity within the
      family.

PMID- 15504270
TI  - Geographic and temporal trends in influenzalike illness, Japan, 1992-1999.
AB  - From 1992 to 1999, we analyzed >2.5 million cases of influenzalike illness (ILI).
      Nationwide influenza epidemics generally lasted 3-4 months in winter. Kriging
      analysis, which illustrates geographic movement, showed that the starting areas
      of peak ILI activity were mostly found in western Japan. Two spreading patterns,
      monotonous and multitonous, were observed. Monotonous patterns in two seasons
      featured peak ILI activity that covered all of Japan within 3 to 5 weeks in
      larger epidemics with new antigenic variants of A/H3N2. Multitonous patterns,
      observed in the other five seasons, featured peak ILI activity within 12 to 15
      weeks in small epidemics without new variants. Applying the kriging method
      allowed better visualization and understanding of spatiotemporal trends in
      seasonal ILI activity. This method will likely be an important tool for future
      influenza surveillance in Japan.

PMID- 15504271
TI  - Epidemiology and cost of nosocomial gastroenteritis, Avon, England, 2002-2003.
AB  - Healthcare-associated outbreaks of gastroenteritis are an increasingly recognized
      problem, but detailed knowledge of the epidemiology of these events is lacking.
      We actively monitored three hospital systems in England for outbreaks of
      gastroenteritis in 2002 to 2003. A total of 2,154 patients (2.21 cases/1,000
      hospital-days) and 1,360 healthcare staff (0.47 cases/1,000-hospital-days) were
      affected in 227 unit outbreaks (1.33 outbreaks/unit-year). Norovirus, detected in
      63% of outbreaks, was the predominant etiologic agent. Restricting new admissions
      to affected units resulted in 5,443 lost bed-days. The cost of bed-days lost plus
      staff absence was calculated to be 635,000 pounds sterling (US. 1.01 million
      dollars) per 1,000 beds. By our extrapolation, gastroenteritis outbreaks likely
      cost the English National Health Service 115 million pounds sterling (US 184
      million dollars) in 2002 to 2003. Outbreaks were contained faster (7.9 vs. 15.4
      days, p = 0.0023) when units were rapidly closed to new admissions (<4 days).
      Implementing control measures rapidly may be effective in controlling outbreaks.

PMID- 15504272
TI  - Fatal Naegleria fowleri meningoencephalitis, Italy.
AB  - We report the first case of primary amebic meningoencephalitis in Italy, in a 9
      year-old boy. Clinical course was fulminant, and diagnosis was made by
      identifying amebas in stained brain sections and by indirect immunofluorescence
      analysis. Naegleria fowleri was characterized as genotype I on the basis of
      polymerase chain reaction test results.

PMID- 15504273
TI  - Scrub typhus in the Republic of Palau, Micronesia.
AB  - In October 2001, an outbreak of febrile illness began in the southwest islands
      group of the Republic of Palau. Through October 2003, a total of 15 southwest
      islanders experienced fever >39.5 degrees C and abdominal distress, both lasting
      >7 days. Orientia tsutsugamushi, the agent of scrub typhus, was subsequently
      identified as the cause.

PMID- 15504274
TI  - Long-term SARS coronavirus excretion from patient cohort, China.
AB  - This study investigated the long-term excretion of severe acute respiratory
      syndrome-associated coronavirus in sputum and stool specimens from 56 infected
      patients. The median (range) duration of virus excretion in sputa and stools was
      21 (14-52) and 27 (16-126) days, respectively. Coexisting illness or conditions
      were associated with longer viral excretion in stools.

PMID- 15504275
TI  - Campylobacteriosis, Eastern Townships, Quebec.
AB  - Independent risk factors for campylobacteriosis (eating raw, rare, or undercooked
      poultry; consuming raw milk or raw milk products; and eating chicken or turkey in
      a commercial establishment) account for <50% of cases in Quebec. Substantial
      regional and seasonal variations in campylobacteriosis were not correlated with
      campylobacter in chickens and suggested environmental sources of infection, such
      as drinking water.

PMID- 15504276
TI  - Laboratory-acquired brucellosis.
AB  - We report two laboratory-acquired Brucella melitensis infections that were shown
      to be epidemiologically related. Blood culture isolates were initially
      misidentified because of variable Gram stain results, which led to misdiagnoses
      and subsequent laboratory exposures. Notifying laboratory personnel who
      unknowingly processed cultures from brucellosis patients is an important
      preventive measure.

PMID- 15504277
TI  - Emerging enteropathogenic Escherichia coli strains?
AB  - Escherichia coli strains of nonenteropathogenic serogroups carrying eae but
      lacking the enteropathogenic E. coli adherence factor plasmid and Shiga toxin DNA
      probe sequences were isolated from patients (children, adults, and AIDS patients)
      with and without diarrhea in Brazil. Although diverse in phenotype and genotype,
      some strains are potentially diarrheagenic.

PMID- 15504278
TI  - Escherichia coli O157 cluster evaluation.
AB  - We investigated a multistate cluster of Escherichia coli O157:H7 isolates; pulsed
      field gel electrophoresis subtyping, using a single enzyme, suggested an
      epidemiologic association. An investigation and additional subtyping, however,
      did not support the association. Confirmating E. coli O157 clusters with two or
      more restriction endonucleases is necessary before public health resources are
      allocated to follow-up investigations.

PMID- 15504279
TI  - Mycobacterium triplex pulmonary disease in immunocompetent host.
AB  - Mycobacterium triplex, a recently described, potentially pathogenic species,
      caused disease primarily in immunocompromised patients. We report a case of
      pulmonary infection due to this mycobacterium in an immunocompetent patient and
      review the characteristics of two other cases. In our experience, Mycobacterium
      triplex pulmonary infection is unresponsive to antimycobacterial chemotherapy.

PMID- 15504280
TI  - Arcobacter species in humans.
AB  - During an 8-year study period, Arcobacter butzleri was the fourth most common
      Campylobacter-like organism isolated from 67,599 stool specimens. Our
      observations suggest that A. butzleri displays microbiologic and clinical
      features similar to those of Campylobacter jejuni; however, A. butzleri is more
      frequently associated with a persistent, watery diarrhea.

PMID- 15504281
TI  - Mycobacterium goodii infections associated with surgical implants at Colorado
      hospital.
AB  - From February to October 2003, Mycobacterium goodii wound infections were
      identified among three patients who received surgical implants at a Colorado
      hospital. This report summarizes the investigation of the first reported
      nosocomial outbreak of M. goodii. Increased awareness is needed about the
      potential for nontuberculous mycobacteria to cause postoperative wound
      infections.

PMID- 15504282
TI  - Nosocomial acquisition of dengue.
AB  - Recent transmission of dengue viruses has increased in tropical and subtropical
      areas and in industrialized countries because of international travel. We
      describe a case of nosocomial transmission of dengue virus in Germany by a
      needlestick injury. Diagnosis was made by TaqMan reverse transcription-polymerase
      chain reaction when serologic studies were negative.

PMID- 15504283
TI  - Novel recombinant sapovirus.
AB  - We determined the complete genome sequences of two sapovirus strains isolated in
      Thailand and Japan. One of these strains represented a novel, naturally occurring
      recombinant sapovirus. Evidence suggested the recombination site was at the
      polymerase-capsid junction within open reading frame one.

PMID- 15504284
TI  - [An attempt to approach an optional therapeutic regimen for chronic hepatitis B].

PMID- 15504285
TI  - [Efficacy of interferon-alpha therapy for HBeAg-negative chronic hepatitis B and
      its influencing factors].
AB  - OBJECTIVE: To investigate the efficacy of interferon-alpha (IFN-alpha) therapy
      for HBeAg-negative chronic hepatitis B. METHODS: Sixty-five Chinese HBeAg
      negative chronic hepatitis B patients were treated with 5 MU recombinant rIFN
      alpha 1b subcutaneously thrice weekly for 5 to 24 months, followed by 12 months
      of treatment-free follow-up; one hundred and eighty-eight Chinese HBeAg-positive
      patients served as controls. For each patient, serum alanine transaminase (ALT)
      was measured biochemically and serum HBV DNA level was detected with fluorescent
      quantitative PCR, HBeAg with enzymoimmunoassay every 1 to 3 months during therapy
      and during the follow-up period. HBeAg loss (only for HBeAg-positive cases), HBV
      DNA undetectable, and ALT normalization: the three together were considered a
      combined response. RESULTS: Rates of combined response were similar in HBeAg
      negative patients (58.5%, 38/65) or HBeAg-positive ones at the end of treatment
      (weighted chi square test, chi2 = 1.878, P<0.05), but were higher at the end of
      the follow-up period in the HBeAg-negative cases (75.4%, 49/65) (weighted chi
      square test, chi2 = 4.796, P<0.05). Furthermore, relapse rates at the end of the
      follow-up period, were also similar in HBeAg-negative patients (15.8%, 6/38) or
      HBeAg positive (chi2 = 0.205, P>0.05). Combined response was achieved at a median
      of 6.0 months (2-16 months) of treatment course in HBeAg-negative patients while
      at a median of 6.0 months (1-22 months) in HBeAg-positive cases (Z = -0.186,
      P>0.05, by the Wilcoxon rank sum test). The only factor predictive of combined
      response, by binary logistic regression analysis, was inflammatory activity in
      the liver biopsy. Gender, age, baseline ALT level, baseline HBV DNA level, and
      anti-HBe were not predictive factors. CONCLUSION: Interferon-alpha therapy
      induces a similar primary and sustained response in HBeAg-negative and in HBeAg
      positive chronic hepatitis B patients.

PMID- 15504286
TI  - [Occurrence and predictive factors of hepatitis B virus polymerase YMDD variation
      among patients with chronic hepatitis B and liver cirrhosis during lamivudine
      therapy].
AB  - OBJECTIVE: To study the incidence and the predictive factors of HBV polymerase
      YMDD variation among patients with chronic hepatitis B and liver cirrhosis during
      lamivudine therapy. METHODS: The clinical data and serial sera of 313 chronic HBV
      infected patients (249 chronic hepatitis B and 64 liver cirrhosis) treated with
      lamivudine were collected. YMDD variations were determined by mispairing PCR-RFLP
      assay. The data were analyzed using SPSS software. RESULTS: The cumulative rates
      of variation among patients with chronic hepatitis B and liver cirrhosis were
      8.84% and 17.19%, 20.91% and 32.40%, 26.92% and 39.56%, 26.92% and 58.79% after
      12, 24, 36 and 48 months of lamivudine treatment, respectively. The results of
      log-rank test and Cox's proportional hazard model analysis indicated that
      lamivudine monotherapy, low ALT level, high HBV DNA level, and the patients with
      liver cirrhosis at baseline were significantly related to an occurrence of YMDD
      variation. CONCLUSION: This study suggests that lower ALT and higher HBV DNA
      levels at baseline before lamivudine treatment, lamivudine monotherapy without
      combining alpha-interferon, and the patients with liver cirrhosis seem to be
      statistically significant for predicting the occurrence of YMDD variation.

PMID- 15504287
TI  - [A clinical study of the efficacy and safety of secretory human interferon alpha
      2a treatment for chronic hepatitis B].
AB  - OBJECTIVE: To investigate the efficacy and safety of secreted interferon in
      treatment of chronic hepatitis B. METHODS: A multi-center randomized open-label
      controlled clinical trial was carried out. The patients of the study group were
      treated by secretory human interferon alpha-2a, and the patients of the control
      group were treated with an ordinary interferon. RESULTS: ALT normalization rate
      in the secreted interferon group was 48.3% and it was higher at the end of
      treatment than that of the control group, but there was no difference between the
      two groups at the end of the follow-up. HBV DNA dropped more in the study drug
      group, but there was no difference in the normalization rate between the two
      groups. HBeAg seroconversions in secreted interferon group and in the control
      interferon group were 19.0% and 18.4% respectively. The safety of the two types
      of interferon was satisfactory. CONCLUSIONS: Secreted interferon was superior to
      ordinary interferon in ALT normalization and HBV DNA drop at the end of treatment
      in chronic hepatitis B patients, but there was no difference at the end of the
      follow-up. There was also no difference in HBeAg negative and HBeAg
      seroconversion between the two groups.

PMID- 15504288
TI  - [Clinical study of lamivudine and interferon combinate administration to inhibit
      hepatitis B virus replication].
AB  - OBJECTIVE: To explore a new strategy for effective and economical anti-virus
      therapy for HBV infection, we conducted a sequence administration of lamivudine
      and interferon alpha 1b to evaluate its effects on HBV replication and rebound as
      well as YMDD mutation induced by lamivudine. METHODS: 150 HBV patients having at
      least 6 months history of infection were assigned randomly into 5 groups. Each
      group of these patients was either treated with lamivudine, interferon alpha 1b,
      lamivudine combined with interferon, sequence administration of lamivudine and
      interferon (sequence group) or no anti-virus therapy (control group) for 12
      months. The serum samples were collected at 0, 3, 6, 9, 12 and 18th months and
      were assayed for ALT, AST, HBeAg, HBV DNA (quantitive PCR) as well as YMDD
      mutation types by microarray. RESULTS: The anti-virus replication effects were
      shown as early as the 3rd month in the sequence group but not in the IFN and
      control groups. The significant and persistent inhibition effect of it on HBV
      replication and improvement of liver function was shown. It was more effective
      than lamivudine or IFN treatments at the end of the drug administration and 6
      months later after the drug was withdrawn. We also found that this sequence
      administration pattern can significantly shorten the period of treatment of
      lamivudine as well as reduce the rate of YMDD mutation and rebound of HBV
      replication after lamivudine withdrawal. It is also more economical than a
      combined therapy of lamivudine with IFN. CONCLUSION: This sequence administration
      of lamivudine and IFN pattern can significantly improve the anti-virus effect on
      HBV replication, shorten the period of treatment with lamivudine, reduce the
      mutation rate of YMDD and prevent the rebound of HBV after drug withdrawal.

PMID- 15504289
TI  - [Oxymatrine in the treatment of chronic hepatitis B for one year: a multicenter
      random double-blind placebo-controlled trial].
AB  - OBJECTIVE: To evaluate the efficacy and safety of oxymatrine in the treatment of
      chronic hepatitis B. METHODS: A multicenter randomized double-blind placebo
      controlled trial was conducted. A total of 144 patients with chronic hepatitis B
      entered the study for 52 weeks; of them 72 received oxymatrine, and 72 received a
      placebo. Before and after the treatment, clinical symptoms, liver function, serum
      hepatitis B virus markers, and adverse drug reactions were observed. RESULTS: In
      144 patients, 14 were dropped and excluded due to inconsistencies in the included
      standard. Therefore, the efficacy and safety of 130 patients were analyzed. After
      being treated for 52 weeks, 70.77% of the patients in the study group had a
      normal ALT level, and in 43.08% and 33.33% their HBV DNA and HBeAg became
      negative. In the placebo group, 39.68% had normal ALT level, and 12.31% and 3.33%
      had their HBV DNA and HBeAg become negative. The rates of complete response and
      partial response in the oxymatrine group were 23.08% and 58.46%, and in the
      placebo group they were 3.08% and 44.62%. They were significantly higher in the
      oxymatrine group than in the placebo group. In the oxymatrine treated patients,
      12 weeks after its withdrawal, 60.00% had a normal ALT level, 41.54% and 23.33%
      had both HBV DNA and HBeAg negative. In the placebo group, 31.75% had a normal
      ALT level, 3.08% and 1.67% had both HBV DNA and HBeAg negative. The rates of
      complete response and partial response in the oxymatrine group were 21.54% and
      47.69%, and in the placebo group they were 0 and 41.54%. They were significantly
      higher in the study group than in the placebo group. The adverse reaction rates
      of oxymatrine in the study and the placebo group were 7.69% and 6.15%,
      respectively, but there was no statistical significant difference between them.
      CONCLUSION: Oxymatrine is an effective and safe agent for the treatment of
      chronic hepatitis B.

PMID- 15504290
TI  - [Clinical characteristics of and the related factors to the relapse of chronic
      hepatitis B after lamivudine withdrawal].
AB  - OBJECTIVES: To investigate the cases of chronic hepatitis B relapse after
      lamivudine withdrawal, and to find clinical characteristics and related factors
      to them. METHODS: 46 cases of chronic hepatitis B relapse after lamivudine
      withdrawal were investigated and followed up. The diagnosis and the course of the
      diseases before therapy with lamivudine, the dosage, effects, period of
      treatment, the reasons for lamivudine withdrawal, the biochemistry, immunological
      and virulogical data in each period, YMDD mutation, pre-C mutation and prognosis
      after relapse were recorded. RESULTS: The periods of treatment of 32.6% of
      patients in this group were shorter than 52 weeks. The HBV DNA of 93.6% of
      patients turned negative at the time of lamivudine withdrawal and returned to
      positive in all of those patients when relapsed; of the 6.4% of patients who did
      not turn negative at the time of lamivudine withdrawal, their HBV DNA was
      elevated more than 2 log when relapsed. A majority of patients (71.7%) did not
      ask their physicians when they decided to withdraw from lamivudine. There were
      61.5% of the other patients who withdrew from lamivudine on the advice of
      physicians but they were not followed up. The state of their illness in 71.7%
      (33/46) patients was more severe than before their lamivudine therapy. In these
      cases, the YMDD mutation was detected in 78.8% of patients (chi2 = 23.23,
      P<0.01), and pre-C mutation was detected in 84.8% of patients (chi2 = 21.04,
      P<0.01), higher than that in the cases with aggrevation of their illnesses before
      the lamivudine therapy. The median time between lamivudine withdrawal and relapse
      was 12 weeks; it was negatively correlated with ALT (r = 0.32, P<0.05) detected
      at the time of lamivudine withdrawal. The severity of the illness at the time of
      relapse was related with age (r = 0.40, P<0.01) and YMDD mutation (r = 0.31,
      P<0.05). The prognosis was related with the age of the patient (r = 0.49,
      P<0.01), the diagnosis (r = 0.39, P<0.01), TBil (r = 0.46, P<0.05) and ALT (r =
      0.32, P<0.05) detected before lamivudine therapy, HBeAg became negative when
      lamivudine was withdrawn (r = 0.31, P<0.05), TBil (r = 0.55, P<0.01) and PTA (r =
      0.57, P<0.01) detected when relapsed. CONCLUSION: A majority of patients did not
      follow the lamivudine treatment recommendation of the experts group on lamivudine
      clinical practice in China. The major reason for relapse perhaps was revived HBV
      DNA multiplication, which induces damage of hepatocytes after lamivudine
      withdrawal. The YMDD mutation and/or pre-C mutation may be one of the factors
      that aggravate the damage of hepatocytes during the relapse. The factors
      including age of the patient, diagnosis before the treatment, TBil and ALT
      detected before lamivudine therapy, HBeAg turning to negative when lamivudine is
      withdrawn, and TBil and PTA detected during relapse may all impact the prognosis.

PMID- 15504291
TI  - [The effect of angiotensin II type 1 receptor blocker valsartan in preventing
      hepatic fibrosis induced by dimethylnitrosamine in rats].
AB  - OBJECTIVE: To observe the effects of angiotensin II type 1 receptor blocker
      valsartan in preventing hepatic fibrosis induced by dimethylnitrosamine in rats.
      METHODS: Except rats in the control group, all were given intraperitoneal
      injections of 1% dimethylnitrosamine (DMN 1 ml/kg, two or three consecutive
      days/a week for 6 weeks). From the first day of the intraperitoneal injection,
      rats in treatment groups were given valsartan for 8 weeks by gastric gavage.
      Liver tissue and blood samples of all rats were examined at 56 days (8 weeks).
      AngII levels were determined by radioimmunoassay. Hepatic mRNA levels of Collagen
      type I (Col I) and tissue inhibitor of metalloproteinase1 (TIMP1) were evaluated
      by reverse-transcription polymerase chain reaction (RT-PCR). RESULTS: Valsartan
      significantly attenuated the degree of liver fibrosis and decreased the hepatic
      AngII content compared with DMN treated rats (P<0.01). mRNA levels of Col I and
      TIMP1 were upregulated in DMN treated rats compared with normal rats. Valsartan
      downregulated the elevation of Col I and TIMP1 mRNA levels (P<0.01). CONCLUSION:
      Hepatic AngII content of the model group was increased, the local tissue RAS was
      activated in DMN induced liver fibrosis. Valsartan can retard the progression of
      hepatic fibrosis and may provide an effective new strategy for anti-liver
      fibrosis therapy.

PMID- 15504292
TI  - [Effects of nitric oxide synthase inhibitor on oxidation/antioxidation system in
      rat livers with alcoholic hepatic steatosis].

PMID- 15504293
TI  - [Expression of type I inositol 1,4,5-triphosphate receptor on rat glomerular and
      afferent arterioles in a model of liver cirrhosis].
AB  - OBJECTIVE: To study the expression of type I inositol 1,4,5-triphosphate receptor
      in rat glomerular and afferent arterioles in a model of liver cirrhosis and study
      the role of cross-membrane message transduction in the pathogenesis of
      hepatorenal syndrome. METHODS: In a rat model of carbontetrachloride liver
      cirrhosis, the expression of type I inositol 1,4,5-triphosphate receptor (IP3R)
      on glomerular and afferent arterioles was measured by immunohistochemical method.
      RESULTS: In the experimental group, 30 rats were used to make a model of liver
      cirrhosis. 11 rats survived during the experiment. The expression of type I IP3R
      on glomerular and afferent arterioles was 4.97+/-1.34 and 4.09+/-1.14 in the
      liver cirrhosis group, and it was 2.43+/-1.67 and 1.83+/-1.32 in the normal
      control rats. The differences between these two groups are statistically
      significant (t = 2.28, P = 0.0458). CONCLUSION: Expression of type I IP3 receptor
      on rat glomerular and afferent arterioles in a model of liver cirrhosis indicated
      that the mechanism of cross-membrane message transduction plays a very important
      role in the pathogenesis of hepatorenal syndrome.

PMID- 15504294
TI  - [Dynamic evolution of MMP-13, TIMP-1, type I and III collagen and their
      interaction in experimental liver fibrosis].
AB  - OBJECTIVE: To obtain a detailed pattern of the dynamic evolution and interactions
      among MMP-13, TIMP-1, type I and III collagen during experimental liver fibrosis.
      METHODS: Wistar rats were randomly allocated into a normal group, and a model
      group. To induce liver fibrosis, rats were intraperitoneally injected with
      dimethylnitrosamine (DMN) three consecutive times in the first week, then two
      consecutive times per week, totally for 6 weeks. In the normal control group,
      rats were treated with saline by the same means. Animals were sacrificed 1, 4,
      10, 17, 28, 42, 56 days after starting DMN injections. Conventional histological
      examinations were performed after hematoxylin and eosin, and Masson stain.
      Fibrosis stages were classified into 0 to 4. Hydroxyproline contents were
      determined after liver tissues were hydrolyzed in HCl at 160 degrees C for 2 h
      and then measured with spectrometry at 560 nm wavelength. mRNA levels of MMP-13,
      TIMP-1, type I and III collagen were determined by semi-quantitive RT-PCR.
      RESULTS: In the model group, hepatic type I pro-collagen mRNA expression started
      to increase on the 10th day after DMN administration (t = 2.85, P < 0.05), type
      III started to increase on the 28th day (t = 4.16, P< 0.01), and TIMP-1 mRNA
      expression started to increase on the 4th day (t = 2.60, P < 0.05). They all
      remained much higher than in the normal group throughout the remaining study
      period. Hepatic MMP-13 mRNA expression started to increase on the 17th day after
      DMN administration and remained at a higher level than in the normal group until
      he 28th day (t = 4.08, P < 0.01), then gradually returned to normal level at the
      end of the study period. CONCLUSION: Although hepatic MMP-13 expression
      transiently increased during liver fibrosis, enhanced expression of TIMP-1 from
      the early periods of liver fibrosis inhibited the collagen degrading ability of
      MMP-13, therefore, over-expressed collagen accumulated in the liver. Thus, it is
      hypothesized that TIMPs play a pivotal role in liver fibrosis.

PMID- 15504296
TI  - [Adenovirus mediated expression of interleukin 12 regulating hepatitis C virus E2
      gene immunization-induced immune response].
AB  - OBJECTIVE: To observe the regulating effect of hepatitis C virus (HCV) envelop
      (E) 2 gene immunization-induced immune responses by adenovirus mediated
      interleukin 12 (IL-12). METHODS: HCV E2 protein was expressed and purified from
      NIH 3T3 and then used as an antigen to detect antibodies against HCV E2. With
      51Cr release, SP2/0 expressing HCV E2 was used as target cell to detect specific
      cytotoxic T lymphocytes (CTL) response; adenovirus recombined IL-12 was
      propagated by 293 cell. HCV E2 recombinant and adenovirus recombined IL-12 were
      injected into the quadriceps femoris muscles and abdominal cavities of 6-8 weeks
      old BALB/C mice. Sera were collected at 2, 3, and 4 weeks and detected for
      antibodies for E2. Spleen cells isolated at 4 weeks were analyzed for specific
      CTL response. RESULTS: It was found that expression of IL-12 at an undetectable
      level did enhance HCV E2 gene immunization-induced CTL activity and there was no
      effect on its hormonal immune response. CONCLUSION: Using adenovirus to express
      interleukin 12 was helpful for regulation of HCV E2 gene immunization-induced
      immune response. Combined HCV E2 and IL-12 can render a strong anti-HCV CTL
      activity and may be of use in the development of HCV gene vaccine in the future.

PMID- 15504295
TI  - [Hammerhead ribozyme against human telomerase catalytic subunit (hTERT) induced
      apoptosis of liver cancer cells].
AB  - OBJECTIVE: To construct vector pEGFP-C1-hTERT-ribozyme (pGTRz-U6) and its mutant
      (pGTmRz-U6) against hTERT containing U6 promoter, then transfect them into human
      liver cancer cell line SMMC7721 to observe the action of the human telomerase
      catalytic subunit (hTERT) hammerhead ribozyme on proliferation and apoptosis of
      human liver cancer cell SMMC7721. METHODS: Eukaryotic expressing vector pGTRz-U6
      and mutant pGTmRz-U6 were constructed and transfected into SMMC7721 using
      Lipofectamine2000 Reagent, with pEGFP-C1 as the control group. After strict
      screening by G418, positive clones were cultured; the amount of expression of
      ribozyme and hTERT was detected by RT-PCR; cell proliferation by MTT; telomerase
      activity by TRAP and silver staining assay; cell apoptosis by FCM. RESULTS: We
      found that the two ribozymes were expressed persistently in SMMC7721; different
      expression levels (P < 0.01) of hTERT among SMMC7721-Rz, SMMC7721-mRz and
      SMMC7721-pEGFP-C1 was exhibited by the analysis of variance with SPSS software.
      The difference between SMMC7721-Rz and the others is significant in t-test (P <
      0.01), while there was no difference between SMMC7721-mRz and SMMC7721-pEGFP-C1
      (P > 0.05). With the advance of cell division, telomerase activities of the cells
      treated by SMMC7721-Rz and SMMC7721-mRz decreased gradually, and the percentage
      of apoptosis of the cells transfected with Rz and mRz increased gradually. The
      apoptosis percentage of 7PDS SMMC7721-Rz was 29.86%, while those of SMMC7721-mRz
      and SMMC7721-pEGFP-C1 were 9.87% and 3.36%, respectively. CONCLUSION: The
      apoptosis level of SMMC7721 induced by hTERT ribozyme increases as cells divide,
      and this ribozyme maybe a potential approach for liver cancer gene therapy.

PMID- 15504297
TI  - [Therapeutic strategies for chronic hepatitis B recommended by the American
      Association for the Study of Liver Diseases].

PMID- 15504298
TI  - [Long-term treatment of chronic hepatitis B and the strategy of anti-virus
      treatment].

PMID- 15504299
TI  - [Several important issues in the antiviral therapy of hepatitis B].

PMID- 15504300
TI  - [Lamivudine therapy for prevention of chemotherapy-induced reactivation of
      hepatitis B virus].

PMID- 15504301
TI  - [An improved method of isolating and identifying rat hepatic stellate cells].

PMID- 15504302
TI  - [A study on the methylation of RIZ1 in hepatocellular carcinomas].

PMID- 15504303
TI  - [The role of enterogenous endotoxemia in the pathogenesis of non-alcoholic
      steatohepatitis].

PMID- 15504304
TI  - [Isolation, cultivation and identification of liver sinusoidal endothelial cells
      in rats].

PMID- 15504305
TI  - [Therapeutic efficacy of Chinese traditional medicine in the treatment of
      fulminate hepatitis].

PMID- 15504306
TI  - [Relationship of peroxisome proliferator-activated receptor with the replication
      of hepatitis B virus and liver fibrosis].

PMID- 15504307
TI  - [Pathological study of non-neoplatic liver cysts].

PMID- 15504308
TI  - [The effect of rabeprazole on gastric pH in patients with gastric ulcer].
AB  - OBJECTIVE: To evaluate the effect of a single dose of rebeprazole (RAB) versus
      omeprazole (OME) on acid suppression and symptom relief in patients with gastric
      ulcer. METHODS: In this randomized, paralleled, double-blind, controlled study,
      177 patients with active gastric ulcer confirmed by endoscopy received a single
      dose of either RAB 10 mg (n = 89) or OME 20 mg (n = 88). Using 24 h pH
      monitoring, the percentage of time with intragastric pH > 3 and pH > 4 was
      calculated for daytime (08:30-21:00), night-time (21:00-08:30) and total 24 h
      period. The symptoms improvement was analyzed before and after using RAB and OME.
      RESULTS: (1) There were no differences in improvement of symptoms between two
      groups (P > 0.05). (2) The percentage of time with pH > 3 and pH > 4 at night
      time, and pH > 4 in the total 24 h period were significantly higher with RAB than
      with OME (P < 0.05). (3) The percentage of patients with pH > 3 over 30% of
      daytime, night-time and 24 h total period was significantly higher with RAB than
      with OME, also as intragastric pH > 4 over 30% of daytime and night-time. (4)
      Percentage of poor responders to acid suppression with RAB (pH > 3 for < 30% of
      the 24 h period) was significantly lower compared with OME (7.8% vs 16.4%,
      respectively, P < 0.05). CONCLUSIONS: One dose of RAB (10 mg) and OME (20 mg)
      could improve symptoms in patients with gastric ulcer, however RAB provides
      superior acid suppression compared with OME, especially on night-time period.

PMID- 15504309
TI  - [Left ventricular mass and function in growth hormone deficient children and
      adolescents before and after one year of recombinant human growth hormone (GH)
      replacement therapy].
AB  - A total of 25 patients (10 girls and 15 boys) aged 8.1-16.9 years (mean 13.3+/
      1.8 years), height 1.15-1.61 m (mean 1.4+/-0.1 m), body area 0.84-1.47 m2 (mean
      1.14+/-0.18 m2) were examined in our study. After 12-month--rhGH therapy, 23
      children (9 girls and 14 boys) were re-evaluated. Twenty two healthy and slim
      children (11 girls and 11 boys) aged 6.6-16 years (mean 12,6+/-2.7 years), height
      1.33-1.8 m (mean 1.58+/-0.16), body area 0.93-1.8 m2 (mean 1.38+/-0.3 m2) with a
      family history without atherosclerosis and cardiovascular diseases constituted
      controls. Mass and function of LV were evaluated by means of M-mode and 2D
      echocardiography and the Doppler method with simultaneous 2D picture recording.
      Systolic function parameters (SF and EF) were normal in each patient before
      therapy. LV systolic fraction (SF) equaled on average 35.4+/-4.5 % in the
      examined group and 36.7+/-3.9 % in controls. LV ejection fraction (EF) was on
      average 65.1+/-5.9 % in the examined group and 67.9+/-6.4 % in controls. The
      differences noted were not statistically significant. After a year-rhGH therapy,
      SF and EF were within a normal range in each patient. SF was on average 35.9+/
      3.6% in the examined group and 36.7+/-3.9% in controls. EF was on average 65.7+/
      4.6% in the examined group and 67.9+/-6.4% in controls. The differences were not
      statistically significant. SF and EF did not differ before and after rhGH
      therapy. LV mass indexed by body superficial area (LVA/BSA) equaled 68.3+/-18.6
      g/m2 before therapy and did not differ significantly in comparison with controls
      (68.2+/-15.5 g/m2). After a year-GH therapy, LV/BSA was significantly higher when
      compared to LV/BSA mass before therapy (78.2+/-14.9 g/m2 vs 68.3+/-18 6 g/m2,
      p<0.05). After a year-GH therapy LV/BSA mass was significantly higher in
      comparison with LV/BSA mass before therapy (78.2+/-14.9 g/m2 vs 68.3+/-18.6 g/m2,
      p< 0.05). Before therapy, IVRT parameter was found significantly extended in
      comparison with controls (70.8+/-14.2 vs 64.1+/-8.5 ms, p<0.05). Other parameters
      characterising LV diastolic function were not significantly different between the
      groups. After a year-GH therapy, IVRT parameter was still extended in comparison
      with controls (72.3+/-9.2 vs 64.1+/-8.5 ms, p<0.05). No significant differences
      were observed with regard to IVRT before and after therapy. CONCLUSION: 1. A
      significant extension of isovolumetric relaxation time (IVRT) was proved in
      children with GH deficiency, which may suggest an impaired diastolic function of
      the heart left ventricle. 2. 12-month-rhGH replacement therapy causes an increase
      in the left ventricle mass when compared to the values before therapy, whereas
      isovolumetric relaxation time remains still longer. 3. Children with GH
      deficiency should have their circulatory system monitored to observe the dynamics
      of the left ventricle functional disorders.

PMID- 15504310
TI  - [Surface expression of costimulatory molecules CD28/CTLA-4 on peripheral blood T
      lymphocytes in the course of type 1 diabetes mellitus in children and
      adolescents].
AB  - BACKGROUND: Type 1 diabetes is mediated by autoreactive - T lymphocytes
      recognizing pancreatic islet cell antigens. CD28/CTLA-4 costimulatory molecules
      participate in the transduction of the necessary signal in T lymphocytes
      proliferation and play an important role in the development of autoimmunological
      process. OBJECTIVES: The purpose of this study was: to evaluate whether the
      expression of CD28, CTLA-4 molecules on peripheral blood T lymphocytes alters in
      the course of disease -- diabetes lasting less than 5 years and over 5 years; to
      assess a relationship between the percentage of CD28, CTLA-4 on T cells and the
      evolution of vascular complications (microalbuminuria, arterial hypertension,
      diabetic retinopathy). MATERIAL AND METHODS: The study was carried out in three
      groups of subjects - 60 children (aged 9-20) with diagnosed type 1 diabetes: (a)
      (20 n) with the disease lasting >5 years, (b) (20 n) with type 1 diabetes lasting
      >5 years without vascular complications, (c) (20 n) with type 1 diabetes and
      vascular complications (microalbuminuria, arterial hypertension, diabetic
      retinopathy). The control group consisted of 20 healthy volunteers (aged 6-17).
      The expression of adhesion molecules has been evaluated by using three-color flow
      cytometry (Coulter EPICS XL). HbA1c concentration has been analysed by liquid
      chromatography technique HPLC-Variant (Bio-Rad). RESULTS: In the study, the
      superficial expression of CTLA-4 receptor on T lymphocytes was enhanced in
      children with diabetes lasting <5 years (p<0.005) and over 5 years without
      vascular complications (p<0.01) versus healthy patients and tend to normalize in
      the presence of developing vascular complications In contrast, the expression of
      costimulatory molecule CD28 was decreased in children with type 1 diabetes
      lasting <5 years (p<0.05) as well as in children with developing vascular
      complications (p<0.01) versus the control group.

PMID- 15504311
TI  - [Homocysteine levels in growth hormone deficient children and adolescents before
      and after one year of recombinant human growth hormone (GH) replacement therapy].
AB  - Growth hormone deficiency is connected with the premature development of the
      cardiovascular system diseases, increased mortality due to the circulatory system
      diseases and the early development of atherosclerosis. An increased concentration
      of homocysteine is recognized as an independent risk factor of atherosclerosis
      and thrombosis. The aim of our study was to evaluate the effect of substitution
      rhGH therapy on homocysteine concentration in children and adolescents with
      growth hormone deficiency. The study included patients with growth hormone
      deficiency diagnosed recently and qualified for rhGH replacement therapy. A total
      of 25 patients (10 girls and 15 boys) aged 8.1-16.9 years (mean 13.3+/-1.8
      years), height 1.15-1.61 m (mean 1.4+/-0.1 m), body area 0.84-1.47 m(2) (mean
      1.14+/-0.18 m(2)) were examined. Twenty two healthy and slim children (11 girls
      and 11 boys) aged 6.6-16 years (mean 12.6+/-2.7 years), height 1.33-1.8 m (mean
      1.58+/-0.16), body area 0.93-1.8 m(2) (mean 1.38+/-0.3 m(2)) with a family
      history without atherosclerosis and cardiovascular diseases constituted controls.
      Homocysteine concentration was determined by means of immunoenzymatic method
      using Axis R Homocysteine kits of BioRad firm. Homocysteine concentration in
      children with GH deficiency did not differ significantly in comparison with
      controls (8.53+/-2.38 vs 8.48+/-2.13 mg/dl). After a year-rh GH therapy, mean
      homocysteine concentration was significantly lower than in controls (7.52+/-2.12
      vs 8.48+/-2.13 mg/dl p<0.05). A significant decrease in homocysteine
      concentration after GH therapy was proved in comparison with the initial values
      in this group (7.52+/-2.12 vs 8.53+/-2.28 mg/dl). CONCLUSIONS: 1. rhGH
      replacement therapy causes a significant decrease in homocysteine concentration
      in children with GH deficiency. 2. Homocysteine concentration in children with GH
      deficiency is one of the factors inducing vessel endothelial damage and further
      biological consequences.

PMID- 15504312
TI  - [Analysis of costimulatory molecules (CD28-CTLA-4/B7) expression on chosen
      mononuclear cells in adolescents with Graves' disease during methimazole
      therapy].
AB  - CD28 and CTLA-4 are glycoprotein molecules providing the potent costimulatory
      signal for T cells activation and proliferation via interactions with their
      ligands B7/BB1 molecule, present on the surface of Ag-presenting cells (APC). The
      present study was performed to elucidate the relationship between CTLA-4/CD28
      molecules and stimulating (TSAb) or blocking (TBAb) antibodies to the TSH
      receptor in Graves' disease. The aim of the study was to estimate the expression
      of CTLA-4 (cytolitic T lymphocyte associated antigen-4, CD152), CD28, B7.1 (CD80)
      and CD7.2 (CD86) molecules on peripheral blood cells in patients with Graves'
      disease (GD) (n=28, mean age 15.4), in patients with nontoxic nodular goiter
      (NTNG) (n=28, mean age 15.6 years) in comparison with sex- and age-matched
      healthy control subjects (n=28, mean age 15.9 years). The expression of the
      costimulatory molecules on mononuclear cells was analyzed by the three-color flow
      cytometry using a Coulter EPICS XL cytometer. Detection of stimulating and
      blocking antibodies to the TSH-receptor using JPO9 CHO cells in unfractionated
      serum was measured by a highly sensitive commercial radioimmunoassay. In
      untreated Graves' patients we observed a significant increase of CD152+ (p<0.004,
      p<0.004, p<0.001) and CD28+ (p<0.02, p<0.02, p<0.02) T lymphocytes in comparison
      to the non-toxic nodular goiter patients, healthy control subjects and euthyroid
      Graves' patients. After 2-6 months of methimazole therapy, the percentages of
      these cells in the peripheral blood of hyperthyroid patients returned to normal
      values. The analysis of CD3+ T lymphocytes co-expressing CD152 and CD28 antigens
      on peripheral blood revealed increased percentages of CTLA-4/CD28 positive cells
      in patients with Graves' disease (p<0.004, p<0.04) compared to the controls and
      euthyroid Graves' patients, while B7.1 (CD80) and B7.2 (CD86) molecules were
      detected only in some hyperthyroid patients on activated monocytes. In addition,
      75% of children with untreated hyperthyroidism had positive TSAbs, whereas TBAbs
      were measured in 3 out of 7 TSAb negative patients with Graves' disease. In
      untreated Graves' patients a correlation between percentage of CD152+ T cells and
      serum level of stimulating and blocking antibodies to the TSH-receptor was found,
      while no such correlation was detected in relation to CD28+ T cells. We conclude
      that the changes of the expression of costimulatory molecules on peripheral blood
      mononuclear cells could be an important marker of activity of an autoimmune
      process in children and adolescents with Graves' disease and that their levels
      are modulated by thyroestatic treatment.

PMID- 15504313
TI  - [Factors affecting C-peptide level during the first year of type 1 diabetes in
      children].
AB  - BACKGROUND: C-peptide level is the most reliable factor evaluating the endogenous
      insulin secretion in patients with type 1 diabetes. OBJECTIVES: The aim of the
      study was to investigate whether the age at onset, gender, presence of
      autoantibodies and ketoacidosis at diagnosis and insulin requirement, HbA1c
      levels could be applied to predict the C-peptide levels in the first year of type
      1 diabetes in children. MATERIAL AND METHODS: 122 type 1 diabetic children, aged:
      2-18 years (average 11.2), 44 female and 78 male were studied. Fasting C-peptide
      levels were examined by radioimmunoassay at diagnosis, after 10 days and after 1,
      2, 3, 6 and 12 months of disease. At diagnosis islet cell antibodies (ICA) were
      detected by indirect immunofluorescence, antibodies to glutamic acid
      decarboxylase (GADA) and tyrosine phosphatase antibodies (IA2A) were measured by
      microradioimmunoprecipitation assay. RESULTS: Age at onset was positively
      correlated to C-peptide levels at each evaluated point of the disease (r=0.3
      0.46, p<0.0001). One year after diagnosis C-peptide levels decreased in ICA(+)
      (p<0.04) and GADA(+) (p<0.002) patients but not in ICA(-) or GADA(-) children.
      There was no significant difference between the IA2A-positive and negative
      subjects in the C-peptide levels at 12th month of disease. C-peptide level was
      also related to ketoacidosis at diagnosis, insulin requirement and HbA1c levels
      during the first year of type 1 diabetes. Logistic regression analysis showed
      that male, younger age, low pH, higher HbA1c and insulin requirement at onset
      were associated with decreased C-peptide level at diagnosis (p<0.00002).
      CONCLUSIONS: Young age, presence of diabetes-related autoantibodies and
      hyperglycaemia with severe acidosis at the disease onset may be associated with a
      decreased residual insulin secretion in type 1 diabetes in children.

PMID- 15504314
TI  - [The model of height prognosis in children with growth hormone deficiency].
AB  - The authors present a test for a prognosis of height in children with
      somatotropic hypofunction of the hypophysis treated with growth hormone. A
      statistic analysis of the height prognosis was performed on support of a model.
      With support of the examinations and the received results the following
      conclusions are proposed: 1. The prognosis of the final height in girls treated
      with growth hormone was statistically significantly lower than boys. 2. The
      longer the time of therapy with growth hormone the significantly higher the
      prognosis of height in these children. 3. In spite of 3 years period of growth
      hormone therapy even with the dose of 0.7 UJ rhGH the children do not achieve
      calculated prognosis of height. 4. Further examinations are necessary including
      more children with total or partial growth hormone deficiency with a longer
      duration of the observation. 5. An analysis of the final height in children after
      interruption of the growth hormone therapy at the age of 18 years is necessary.

PMID- 15504315
TI  - [Transplantation in diabetes type 1--current problems and perspectives].
AB  - Diabetes type 1 is, as we know, a chronic progressive disease, which requires a
      substitutional therapy with insulin for the whole life. The cause is a definite
      destruction of the pancreatic beta cells. For many years there have been
      intensive investigations on the possibility to obtain a complete, persistent
      withdrawal of the symptoms. Substitution of the destroyed, not active cells,
      could take place after transplantation of the whole pancreas, transplantation of
      pancreatic islets or transplantation of stem cells. This is now the only method
      which may cause an independence from exogenous insulin, persistent normoglycemia,
      normal HbA1c level, without risk of hypoglycemia. Pancreas and islets
      transplantations, however, are connected till now with the necessity of an
      immunosuppressive therapy for the whole life, with the toxicity of the drugs,
      incidence of frequent infections and malignancy. Pancreas transplantation is a
      serious surgical intervention, connected with numerous risks and complications,
      considerably less risk appears in islet cell transplantations. Since 2000
      exclusively islet cell transplantations have been performed. One of the leading
      centers is Edmonton, where professor Shapiro prepared the so called. Edmonton
      protocol which is characterized by using corticosteroid-free immunosuppressive
      drugs, islet cells from two or more donors, repeated till the attainment of
      insulin dependence. A problem now is that the islets are obtained from cadavers.
      Therefore intensive research is conducted for alternative sources of beta cells.
      At this moment it is mostly preferred for receiving a sufficient number of
      insulin producing cells to develop stem cells with a subsequent differentiation
      to insulin producing cells. The mentioned cells have an unlimited ability of
      reproduction, in this case also immunosuppressive therapy is not necessary.
      Alternative sources of beta cells are cells achieved on the genetic engineering,
      embryonic or adult somatic stem cells. It is however important to stress, that
      adult stem cells as insulin producing cells are not unequivocally identified. For
      obtaining better, permanent results after transplantation the following are
      important: optimalization of "islands growth" in the liver, prevention of the
      early inflammations, further development of highly selective, well tolerated,
      corticosteroid-free immunosuppressive drugs, identification of rejecting markers,
      induction of immunotolerance, micro- and macro-capsulation of the islets to
      protect the recipient against the immunological attack. Several multicenter
      studies in important scientific centers are opened, there is also Juvenile
      Research Foundation International. In spite of a permanent progress there are
      still many important problems to solve. It is necessary to institute further
      multicenter, international research to ascertain the effect of transplantation
      concerning the normalisation of glycemia, prevention or inhibition of the
      progress of diabetic complications and to prolong the life span in patients with
      type 1 diabetes after transplantation.

PMID- 15504316
TI  - [Personal observations of puberty in girls after unilateral ovariectomy].
AB  - The authors present the course of puberty in three girls after surgery because of
      hormonally active ovarian tumours diagnosed and operated at the age of 3, 6 and 9
      years, respectively. In the youngest patient with folliculoma ovari chemotherapy
      was also given, and girl No. 3 with luteinic capsule was treated for one year
      with decapeptyl because idiopathic precocious puberty was diagnosed. At present
      all three girls are in good physical condition with age-adequate development and
      puberty.

PMID- 15504317
TI  - [Kallmann's syndrome in families].
AB  - The authors present the incidence of Kallmann's syndrome in two families in four
      persons. In one family the syndrome was present in a boy and the brother of his
      mother. In the second family in siblings -- a boy and a girl. The two boys at
      preschool age underwent a surgery because of bilateral cryptorchism. In the first
      patient and his uncle additional hearing dysfunction and agenesis of the left
      kidney were diagnosed. In all the patients anosmia was diagnosed. All the
      patients receive a pharmacological treatment which improved significantly their
      clinical state, caused the development of tertiary sexual feature and an
      improvement of the psychological condition. CONCLUSIONS: 1. In patients with an
      abnormal development of the urethro-sexual organs a diagnosis for other
      disturbances or developmental defects is necessary. 2. In patients with an
      abnormal urethro-sexual development a permanent care of a psychologist is
      necessary.

PMID- 15504318
TI  - [Association of brain computed tomography images of intracranial calcifications
      in three different cases of hypoparathyroidism].
AB  - The problem of intracranial calcifications in children has not been widely
      discussed in the literature yet. The aim of this study is to emphasise different
      clinical aspects of intracranial calcifications found in subcortical nuclei and
      cerebellum in children with disturbed calcium metabolism. We report three
      different cases of hypoparathyroidism in children in whom similar radiological
      changes on computed tomography (CT) of the brain were found. An 11-year-old boy
      was referred to us after episode of tetany. We confirmed the diagnosis of
      idiopatic hypoparathyroidism (presence of Chvostek and Trousseau signs,
      hypocalcemia, hyperphosphatemia, low parathormone serum concentration). On brain
      CT small, symmetric calcifications in the subcortical nuclei and frontal lobes
      were imaged. A diagnosis of pseudohypoparathyroidism type Ib in 10-year-old girl
      was established on the basis of clinical symptoms (syncope with seizures,
      recurrent carpopedal spasms in the past) and laboratory investigations
      (hypocalcemia, hyperphosphatemia, high parathormone serum concentration). In 11
      year-old girl autoimmune polyglandular syndrome type I was diagnosed
      (hypoparathyroidism with chronic mucocutaneous candidiasis and nail dystrophy
      from the age of 2). CT of the brain showed multiple irregular symmetric
      calcifications in cerebellar hemispheres, internal capsula and subcortical nuclei
      on the border of white and grey matter in both frontal lobes.

PMID- 15504319
TI  - Peering into the dendritic machinery of striatal medium spiny neurons.
AB  - Striatal medium spiny neurons are principal players in the basal ganglia
      macrocircuits implicated in an astonishing array of psychomotor disorders,
      including Parkinson's disease, schizophrenia, Huntington's disease, and drug
      abuse. Using an elegant combination of 2-photon laser scanning microscopy and 2
      photon uncaging of glutamate, Carter and Sabatini (this issue of Neuron) provide
      our first glimpse into the dendrites and spines of striatal medium spiny neurons.
      The results offer new insights into the workings of these clinically important
      yet mysterious neurons.

PMID- 15504320
TI  - Dendritic h channelopathy in epileptogenesis.
AB  - Recent work has suggested a link between h channels and epilepsy. In this issue
      of Neuron, Shah et al. demonstrate that a robust, postseizure decrease in h
      channels during a critical phase of epileptogenesis mechanistically underlies
      dendritic hyperexcitability in entorhinal-hippocampal pyramidal cells.

PMID- 15504321
TI  - Diverse mechanisms to remember various odors.
AB  - Two dorsal paired medial (DPM) neurons express the Amnesiac neuropeptide and
      project onto mushroom bodies, the Drosophila olfactory memory center. In this
      issue of Neuron, Keene et al. show that higher-level brain circuits process
      various olfactory memories differently. DPM neurons are required during
      acquisition of some odors and during memory consolidation of others. These
      findings reveal a surprising level of complexity for the formation of olfactory
      memories in Drosophila.

PMID- 15504322
TI  - The number domain- can we count on parietal cortex?
AB  - Does the primate brain contain a dedicated and localized neural circuitry for
      processing generic numerical information? The human parietal cortex, particularly
      the intraparietal sulcus (IPS), has long been implicated in processing symbolic
      (verbal) number information. If the IPS is indeed the site of generic numerical
      processing, however, its neurons should also encode nonsymbolic numerosity
      information. Two recent studies by Shuman and Kanwisher and by Piazza et al.
      published in this issue of Neuron tested this assumption...with quite different
      results.

PMID- 15504323
TI  - Neural changes following remediation in adult developmental dyslexia.
AB  - Brain imaging studies have explored the neural mechanisms of recovery in adults
      following acquired disorders and, more recently, childhood developmental
      disorders. However, the neural systems underlying adult rehabilitation of
      neurobiologically based learning disabilities remain unexplored, despite their
      high incidence. Here we characterize the differences in brain activity during a
      phonological manipulation task before and after a behavioral intervention in
      adults with developmental dyslexia. Phonologically targeted training resulted in
      performance improvements in tutored compared to nontutored dyslexics, and these
      gains were associated with signal increases in bilateral parietal and right
      perisylvian cortices. Our findings demonstrate that behavioral changes in tutored
      dyslexic adults are associated with (1) increased activity in those left
      hemisphere regions engaged by normal readers and (2) compensatory activity in the
      right perisylvian cortex. Hence, behavioral plasticity in adult developmental
      dyslexia involves two distinct neural mechanisms, each of which has previously
      been observed either for remediation of developmental or acquired reading
      disorders.

PMID- 15504324
TI  - Close homolog of L1 modulates area-specific neuronal positioning and dendrite
      orientation in the cerebral cortex.
AB  - We show that the neural cell recognition molecule Close Homolog of L1 (CHL1) is
      required for neuronal positioning and dendritic growth of pyramidal neurons in
      the posterior region of the developing mouse neocortex. CHL1 was expressed in
      pyramidal neurons in a high-caudal to low-rostral gradient within the developing
      cortex. Deep layer pyramidal neurons of CHL1-minus mice were shifted to lower
      laminar positions in the visual and somatosensory cortex and developed
      misoriented, often inverted apical dendrites. Impaired migration of CHL1-minus
      cortical neurons was suggested by strikingly slower rates of radial migration in
      cortical slices, failure to potentiate integrin-dependent haptotactic cell
      migration in vitro, and accumulation of migratory cells in the intermediate and
      ventricular/subventricular zones in vivo. The restriction of CHL1 expression and
      effects of its deletion in posterior neocortical areas suggests that CHL1 may
      regulate area-specific neuronal connectivity and, by extension, function in the
      visual and somatosensory cortex.

PMID- 15504325
TI  - Nogo-66 receptor prevents raphespinal and rubrospinal axon regeneration and
      limits functional recovery from spinal cord injury.
AB  - Axon regeneration after injury to the adult mammalian CNS is limited in part by
      three inhibitory proteins in CNS myelin: Nogo-A, MAG, and OMgp. All three of
      these proteins bind to a Nogo-66 receptor (NgR) to inhibit axonal outgrowth in
      vitro. To explore the necessity of NgR for responses to myelin inhibitors and for
      restriction of axonal growth in the adult CNS, we generated ngr(-/-) mice. Mice
      lacking NgR are viable but display hypoactivity and motor impairment. DRG neurons
      lacking NgR do not bind Nogo-66, and their growth cones are not collapsed by Nogo
      66. Recovery of motor function after dorsal hemisection or complete transection
      of the spinal cord is improved in the ngr(-/-) mice. While corticospinal fibers
      do not regenerate in mice lacking NgR, regeneration of some raphespinal and
      rubrospinal fibers does occur. Thus, NgR is partially responsible for limiting
      the regeneration of certain fiber systems in the adult CNS.

PMID- 15504326
TI  - Quaternary structure, protein dynamics, and synaptic function of SAP97 controlled
      by L27 domain interactions.
AB  - Single-particle electron microscopy (EM) combined with biochemical measurements
      revealed the molecular shape of SAP97 and a monomer-dimer transition that
      depended on the N-terminal L27 domain. Overexpression of SAP97 drove GluR1 to
      synapses, potentiated AMPA receptor (AMPAR) excitatory postsynaptic currents
      (EPSCs), and occluded LTP. Synaptic potentiation and GluR1 delivery were
      dissociable by L27 domain mutants that inhibit multimerization of SAP97. Loss of
      potentiation was correlated with faster turnover of monomeric SAP97 mutants in
      dendritic spines. We propose that L27-mediated interactions of SAP97 with itself
      or other proteins regulate the synaptic delivery of AMPARs. RNAi knockdown of
      endogenous PSD-95 depleted surface GluR1 and impaired AMPA EPSCs. In contrast,
      RNAi knockdown of endogenous SAP97 reduced surface expression of both GluR1 and
      GluR2 and inhibited both AMPA and NMDA EPSCs. Thus SAP97 has a broader role than
      its close relative, PSD-95, in the maintenance of synaptic function.

PMID- 15504327
TI  - Fast endocytosis is inhibited by GABA-mediated chloride influx at a presynaptic
      terminal.
AB  - Although multiple kinetic components of synaptic vesicle endocytosis have been
      identified, it has remained unclear whether neurons can differentially modulate
      these components. Using membrane capacitance measurements from isolated goldfish
      bipolar cell terminals, we found that the kinetics of endocytosis in retinal
      slices (single exponential decay; tau > 10 s) were significantly slower than
      those in acutely dissociated terminals (double exponential decay; tau(fast)
      approximately 1-2 s; tau(slow) > 10 s). Surprisingly, GABA(A) and/or GABA(C)
      receptor antagonists restored the fast component of endocytosis to terminals in
      retinal slices. Blocking GABAergic feedback from reciprocal synapses or removing
      external Cl(-) ions also allowed for fast endocytosis. Elevating internal Cl(-)
      via the patch pipette invariably slowed endocytosis, even in terminals dialyzed
      with increased Ca(2+) buffer. These results suggest a new role for GABA and Cl(-)
      ions in blocking the trigger for fast endocytosis at this ribbon-type synapse.

PMID- 15504328
TI  - State-dependent calcium signaling in dendritic spines of striatal medium spiny
      neurons.
AB  - Striatal medium spiny neurons (MSNs) in vivo undergo large membrane
      depolarizations known as state transitions. Calcium (Ca) entry into MSNs triggers
      diverse downstream cellular processes. However, little is known about Ca signals
      in MSN dendrites and spines and how state transitions influence these signals.
      Here, we develop a novel approach, combining 2-photon Ca imaging and 2-photon
      glutamate uncaging, to examine how voltage-sensitive Ca channels (VSCCs) and
      ionotropic glutamate receptors contribute to Ca signals in MSNs. We find that
      upstate transitions switch the VSCCs available in dendrites and spines,
      decreasing T-type while enhancing L-type channels. Moreover, these transitions
      change the dominant synaptic Ca source from Ca-permeable AMPA receptors to NMDA
      receptors. Finally, pairing bAPs with synaptic inputs generates additional
      synaptic Ca signals due to enhanced Ca influx through NMDA receptors. By altering
      the sources, amplitude, and kinetics of spine Ca signals, state transitions may
      gate synaptic plasticity and gene expression in MSNs.

PMID- 15504330
TI  - Dysregulation of striatal dopamine signaling by amphetamine inhibits feeding by
      hungry mice.
AB  - Amphetamine (AMPH) releases monoamines, transiently stimulates locomotion, and
      inhibits feeding. Using a genetic approach, we show that mice lacking dopamine
      (DA-deficient, or DD, mice) are resistant to the hypophagic effects of a moderate
      dose of AMPH (2 microg/g) but manifest normal AMPH-induced hypophagia after
      restoration of DA signaling in the caudate putamen by viral gene therapy. By
      contrast, AMPH-induced hypophagia in response to the same dose of AMPH is not
      blunted in mice lacking the ability to make norepinephrine and epinephrine (Dbh(
      /-)), dopamine D(2) receptors (D2r(-/-)), dopamine D(1) receptors (D1r(-/-)),
      serotonin 2C receptors (Htr2c(-/Y)), neuropeptide Y (Npy(-/-)), and in mice with
      compromised melanocortin signaling (A(y)). We suggest that, at this moderate dose
      of AMPH, dysregulation of striatal DA is the primary cause of AMPH-induced
      hypophagia and that regulated striatal dopaminergic signaling may be necessary
      for normal feeding behaviors.

PMID- 15504331
TI  - Diverse odor-conditioned memories require uniquely timed dorsal paired medial
      neuron output.
AB  - Amnesiac mutant flies have an olfactory memory defect. The amn gene encodes a
      homolog of vertebrate pituitary adenylate cyclase-activating peptide (PACAP), and
      it is strongly expressed in dorsal paired medial (DPM) neurons. DPM neurons
      ramify throughout the mushroom bodies in the adult fly brain, and they are
      required for stable memory. Here, we show that DPM neuron output is only required
      during the consolidation phase for middle-term odor memory and is dispensable
      during acquisition and recall. However, we found that DPM neuron output is
      required during acquisition of a benzaldehyde odor memory. We show that flies
      sense benzaldehyde by the classical olfactory and a noncanonical route. These
      results suggest that DPM neurons are required to consolidate memory and are
      differently involved in memory of a volatile that requires multisensory
      integration.

PMID- 15504329
TI  - Seizure-induced plasticity of h channels in entorhinal cortical layer III
      pyramidal neurons.
AB  - The entorhinal cortex (EC) provides the predominant excitatory drive to the
      hippocampal CA1 and subicular neurons in chronic epilepsy. Discerning the
      mechanisms underlying signal integration within EC neurons is essential for
      understanding network excitability alterations involving the hippocampus during
      epilepsy. Twenty-four hours following a single seizure episode when there were no
      behavioral or electrographic seizures, we found enhanced spontaneous activity
      still present in the rat EC in vivo and in vitro. The increased excitability was
      accompanied by a profound reduction in I(h) in EC layer III neurons and a
      significant decline in HCN1 and HCN2 subunits that encode for h channels.
      Consequently, dendritic excitability was enhanced, resulting in increased
      neuronal firing despite hyperpolarized membrane potentials. The loss of I(h) and
      the increased neuronal excitability persisted for 1 week following seizures. Our
      results suggest that dendritic I(h) plays an important role in determining the
      excitability of EC layer III neurons and their associated neural networks.

PMID- 15504332
TI  - Are spatial memories strengthened in the human hippocampus during slow wave
      sleep?
AB  - In rats, the firing sequences observed in hippocampal ensembles during spatial
      learning are replayed during subsequent sleep, suggesting a role for posttraining
      sleep periods in the offline processing of spatial memories. Here, using regional
      cerebral blood flow measurements, we show that, in humans, hippocampal areas that
      are activated during route learning in a virtual town are likewise activated
      during subsequent slow wave sleep. Most importantly, we found that the amount of
      hippocampal activity expressed during slow wave sleep positively correlates with
      the improvement of performance in route retrieval on the next day. These findings
      suggest that learning-dependent modulation in hippocampal activity during human
      sleep reflects the offline processing of recent episodic and spatial memory
      traces, which eventually leads to the plastic changes underlying the subsequent
      improvement in performance.

PMID- 15504333
TI  - Tuning curves for approximate numerosity in the human intraparietal sulcus.
AB  - Number, like color or movement, is a basic property of the environment. Recently,
      single neurons tuned to number have been observed in animals. We used both
      psychophysics and neuroimaging to examine whether a similar neural coding scheme
      is present in humans. When participants viewed sets of items with a variable
      number, the bilateral intraparietal sulci responded selectively to number change.
      Functionally, the shape of this response indicates that humans, like other animal
      species, encode approximate number on a compressed internal scale. Anatomically,
      the intraparietal site coding for number in humans is compatible with that
      observed in macaque monkeys. Our results therefore suggest an evolutionary basis
      for human elementary arithmetic.

PMID- 15504334
TI  - Numerical magnitude in the human parietal lobe; tests of representational
      generality and domain specificity.
AB  - Behavioral evidence suggests that human adults have a single system for
      representing the numerical magnitude of both symbolic numbers (e.g., Arabic
      digits) and nonsymbolic number stimuli (e.g., dot arrays). Brain imaging studies
      have implicated a specific parietal region in symbolic number processing, leading
      to the influential hypothesis that this region is the locus of a dedicated,
      domain-specific number system. Here we evaluated a prediction of this hypothesis,
      that this region should be activated not only by symbolic but also nonsymbolic
      number processing. Using nonsymbolic stimuli, we tested for higher parietal
      activations for number than for nonnumber comparison tasks (experiment 1), fMRI
      adaptation for numerosity repetition (experiment 2), and greater fMRI increases
      with increasing task difficulty for number than nonnumber tasks (experiment 3).
      None of these predictions were supported by the data, posing a serious challenge
      to the hypothesis that a single, domain-specific parietal region underlies both
      symbolic and nonsymbolic number representation.

PMID- 15504335
TI  - Src protein-tyrosine kinase structure and regulation.
AB  - Src and Src-family protein kinases are proto-oncogenes that play key roles in
      cell morphology, motility, proliferation, and survival. v-Src (a viral protein)
      is encoded by the chicken oncogene of Rous sarcoma virus, and Src (the cellular
      homologue) is encoded by a physiological gene, the first of the proto-oncogenes.
      From the N- to C-terminus, Src contains an N-terminal 14-carbon myristoyl group,
      a unique segment, an SH3 domain, an SH2 domain, a protein-tyrosine kinase domain,
      and a C-terminal regulatory tail. The chief phosphorylation sites of Src include
      tyrosine 416 that results in activation from autophosphorylation and tyrosine 527
      that results in inhibition from phosphorylation by C-terminal Src kinase. In the
      restrained state, the SH2 domain forms a salt bridge with phosphotyrosine 527,
      and the SH3 domain binds to the kinase domain via a polyproline type II left
      handed helix. The SH2 and SH3 domains occur on the backside of the kinase domain
      away from the active site where they stabilize a dormant enzyme conformation.
      Protein-tyrosine phosphatases such as PTPalpha displace phosphotyrosine 527 from
      the Src SH2 domain and mediate its dephosphorylation leading to Src kinase
      activation. C-terminal Src kinase consists of an SH3, SH2, and kinase domain; it
      lacks an N-terminal myristoyl group and a C-terminal regulatory tail. Its X-ray
      structure has been determined, and the SH2 lobe occupies a position that is
      entirely different from that of Src. Unlike Src, the C-terminal Src kinase SH2
      and SH3 domains stabilize an active enzyme conformation. Amino acid residues in
      the alphaD helix near the catalytic loop in the large lobe of C-terminal Src
      kinase serve as a docking site for the physiological substrate (Src) but not for
      an artificial substrate (polyGlu(4)Tyr).

PMID- 15504336
TI  - An antigen-mediated selection system for mammalian cells that produce
      glycosylated single-chain Fv.
AB  - Selection and production of specific antibodies are limiting the development of
      high-throughput immunoassays such as antibody chips. In this study, we propose an
      antigen-mediated selection of antibody producers (ASAP) system in mammalian
      cells. As a model system, transgenes encoding anti-fluorescein ScFv fused to
      cytokine receptors were introduced to IL-3-dependent cell lines. Addition of
      fluorescein-conjugated BSA induced growth signal through the ScFv/receptor
      chimeras, leading to selective expansion of the transduced cells. Cre recombinase
      was then used to excise the receptor gene flanked by two loxP recognition sites
      in the introns, resulting in secretion of his-myc-tagged ScFv to the culture
      medium. When the first loxP site was used in the exon as a linker between ScFv
      and receptor, enhanced antigen-mediated cell proliferation and production of
      unexpectedly glycosylated ScFv were achieved. ASAP is the first mammalian
      selection/production system of recombinant human ScFvs, without need for
      subcloning and with the advantage of glycosylated product.

PMID- 15504337
TI  - Short hairpin RNA and retroviral vector-mediated silencing of p53 in mammalian
      cells.
AB  - RNA interference (RNAi) is the process of gene silencing, in which the
      recognition of double-stranded RNA ultimately leads to post-transcriptional
      suppression of gene expression. RNAi induced by small interfering RNA (siRNA) or
      short hairpin RNA (shRNA) is an important research approach for the analysis of
      gene function in mammalian cells. Here we established a shRNA expression
      retroviral vector in which the sense and antisense sequences targeting wild type
      human p53 were linked together with a 9-nucleotide loop. Further, we found that
      shRNA expressed from a RNA polymerase III vector based on the human H1 RNA
      promoter could effectively inhibit gene expression in a sequence-specific manner.
      H1-driven shRNA dramatically reduced the expression of wild type human p53 in
      H1299 cells transfected with wtp53. We also found that the retroviral vector
      could circumvent the difficulty in transfection for the delivery of siRNA or
      shRNA and the generation of long-term gene silencing. The use of shRNA expression
      vector for RNAi might provide a rapid and versatile method for assessing gene
      function in mammalian cells with possible applications in the treatment of
      diseases.

PMID- 15504338
TI  - Expression and characterization of the first kunitz domain of human tissue factor
      pathway inhibitor-2.
AB  - Human tissue factor pathway inhibitor-2 (hTFPI-2) has three kunitz domains whose
      structure and function are unclear. We expressed the first kunitz domain of hTFPI
      2 (hTFPI-2/KD1) as functional form using Pichia pastoris and investigated its
      characterization. In the experiment, hTFPI-2/KD1 can inhibit the plasmin and
      trypsin activity and the Ki of hTFPI-2/KD1 towards plasmin (30nM) and trypsin
      (50nM) was determined as 10 and 7nM by chromogenic assay, respectively. hTFPI
      2/KD1 can also inhibit MMP-2 and MMP-9 in zymography assay. Furthermore, the
      inhibition of hTFPI-2/KD1 to the Matrigel invasion by HT-1080 is also described.
      This study provides a method to produce hTFPI-2/KD1 efficiently and some insights
      into the structure and function of hTFPI-2/KD1.

PMID- 15504339
TI  - Silencing of SARS-CoV spike gene by small interfering RNA in HEK 293T cells.
AB  - Two candidate small interfering RNAs (siRNAs) corresponding to severe acute
      respiratory syndrome-associated coronavirus (SARS-CoV) spike gene were designed
      and in vitro transcribed to explore the possibility of silencing SARS-CoV S gene.
      The plasmid pEGFP-optS, which contains the codon-optimized SARS-CoV S gene and
      expresses spike-EGFP fusion protein (S-EGFP) as silencing target and expressing
      reporter, was transfected with siRNAs into HEK 293T cells. At various time points
      of posttransfection, the levels of S-EGFP expression and amounts of spike mRNA
      transcript were detected by fluorescence microscopy, flow cytometry, Western
      blot, and real-time quantitative PCR, respectively. The results showed that the
      cells transfected with pEGFP-optS expressed S-EGFP fusion protein at a higher
      level compared with those transfected with pEGFP-S, which contains wildtype SARS
      CoV spike gene sequence. The green fluorescence, mean fluorescence intensity, and
      SARS-CoV S RNA transcripts were found significantly reduced, and the expression
      of SARS-CoV S glycoprotein was strongly inhibited in those cells co-transfected
      with either EGFP- or S-specific siRNAs. Our findings demonstrated that the S
      specific siRNAs used in this study were able to specifically and effectively
      inhibit SARS-CoV S glycoprotein expression in cultured cells through blocking the
      accumulation of S mRNA, which may provide an approach for studies on the
      functions of SARS-CoV S gene and development of novel prophylactic or therapeutic
      agents for SARS-CoV.

PMID- 15504340
TI  - Amphitrite ornata dehaloperoxidase: enhanced activity for the catalytically
      active globin using MCPBA.
AB  - Dehaloperoxidase (DHP) from Amphitrite ornata is the only heme-containing,
      hydrogen peroxide-dependent globin capable of oxidatively dehalogenating
      halophenols to yield the corresponding quinones. To ascertain that this enzymatic
      activity is intrinsic to DHP, we have cloned and expressed the enzyme in
      Escherichia coli. We also find that an alternate oxygen atom donor, meta
      chloroperbenzoic acid, gives appreciably higher activity than hydrogen peroxide.
      Under optimal turnover conditions (large peroxide/peracid excess), after an
      initial burst of activity, DHP appears to become trapped in a non-catalytic state
      (possibly Compound II) and is unable to fully convert all halophenol to product.
      However, full substrate conversion can be achieved under more physiological
      conditions involving a much smaller excess of oxygen atom donor. Parallel studies
      have been carried out using horseradish peroxidase and myoglobin to calibrate the
      activity of DHP versus typical peroxidase and globin proteins, respectively.

PMID- 15504341
TI  - pH-induced changes of the structure of small heat shock proteins with molecular
      mass 24/27kDa (HspB1).
AB  - The effect of pH on the structure of recombinant chicken Hsp24, human Hsp27 and
      their 3D mutants mimicking phosphorylation at Ser15, Ser77/78, and Ser81/82 was
      analyzed. Circular dichroism and fluorescent spectroscopy indicate that changes
      of pH in the range 6.0-7.5 weakly affected the secondary and tertiary structure
      of the wild type proteins, but induced noticeable changes in the structure of
      their 3D mutants. According to size-exclusion chromatography and analytical
      ultracentrifugation variation of pH-induced pronounced changes in the quaternary
      structure of small heat shock proteins and acidification resulted in accumulation
      of large oligomers of Hsp24/27. It is concluded that small changes of pH strongly
      affect the quaternary structure of small heat shock proteins and by this means
      can influence their functioning in the cell.

PMID- 15504343
TI  - Condensation of chromatin in situ by cation-dependent charge shielding and
      aggregation.
AB  - Binding of di- or polyvalent cations is necessary to maintain the chromatin in
      isolated nuclei and metaphase chromosomes in a condensed state. We here show that
      the native, porous structure of the heterochromatin in the interphase nucleus
      requires both K(+) and Mg(2+) in concentrations, which are known to support
      transcription in isolated nuclei, thus providing a functional state of the
      chromatin. When these cations are acting separately, the chromatin is more
      condensed by Mg(2+) and decondensed by K(+). Comparison with published values of
      the free electrostatic energy of DNA in chromatin shows that this state of
      compaction is the result of a balance between the different aggregative
      properties of K(+) and Mg(2+) at a high degree of charge shielding.

PMID- 15504342
TI  - AMPK inhibits fatty acid-induced increases in NF-kappaB transactivation in
      cultured human umbilical vein endothelial cells.
AB  - The fuel sensing enzyme AMP-activated protein kinase (AMPK) enhances processes
      that generate ATP when stresses such as exercise or glucose deprivation make
      cells energy deficient. We report here a novel role of AMPK, to prevent the
      activation of NF-kappaB in endothelial cells exposed to the fatty acid palmitate
      or the cytokine TNF-alpha. Incubation of cultured human umbilical vein
      endothelial cells (HUVEC) with elevated levels of palmitate (0.4mM) increased NF
      kappaB reporter gene expression by 2- to 4-fold within 8h and caused a 7-fold
      increase in VCAM-1 mRNA expression at 24h. In contrast, no increase in reporter
      gene expression was detected for AP-1, glucocorticoid-, cyclic AMP-, or serum
      response elements. Similar increases in NF-kappaB activation and VCAM-1
      expression were not observed in cells incubated with an elevated concentration of
      glucose (25mM). The increases in NF-kappaB activation and VCAM-1 expression
      caused by palmitate were markedly inhibited by co-incubation with the AMPK
      activator AICAR and, where studied, by expression of a constitutively active
      AMPK. Likewise, AMPK activation inhibited the increase in NF-kappaB reporter gene
      expression observed in HUVEC incubated with TNF-alpha. The results suggest that
      AMPK inhibits the activation of NF-kappaB caused by both palmitate and TNF-alpha.
      The mechanism responsible for this action, as well as its relevance to the
      reported anti-atherogenic actions of exercise, metformin, thiazolidinediones, and
      adiponectin, all of which have been shown to activate AMPK, remains to be
      determined.

PMID- 15504344
TI  - Ceramide kinase targeting and activity determined by its N-terminal pleckstrin
      homology domain.
AB  - The N-terminus of ceramide kinase (CERK) is thought to be myristoylated and to
      contain a pleckstrin homology (PH) domain. We found that deletion of this region
      (DeltaPH-CERK) ablates activity. This is not due to prevention of N-terminal
      myristoylation since a G2A CERK mutant, which cannot be myristoylated, was
      active. CERK was able to bind liposomes, as well as the isolated unmyristoylated
      PH domain; DeltaPH-CERK was not. Upon analysis of EGFP-tagged proteins, CERK was
      found associated with the Golgi complex. Osmotic cell swelling induced
      translocation of CERK to the plasma membrane and formation of large vesicles
      displaying bound CERK. None of these features occurred with DeltaPH-CERK, which
      remained disseminated throughout the cytoplasm. These findings show that the PH
      domain of CERK is essential for localization, translocation, and activity of this
      lipid kinase.

PMID- 15504345
TI  - p38 MAPK signaling pathway is involved in butyrate-induced vitamin D receptor
      expression.
AB  - Previously, we have demonstrated that the butyrate-induced differentiation in the
      human colon cancer cell line Caco-2 occurs via upregulation of the vitamin D
      receptor (VDR). However, the downstream pathways involved are unknown. The
      mitogen-activated protein kinases (MAPKs) have been shown to play an important
      role in regulation of cell differentiation, and may therefore be a potential
      target of butyrate action. To assess their role in butyrate-mediated cell
      differentiation and VDR expression, we used the specific p38-MAPK inhibitor
      SB203580 and the ERK1/2 MAPK-inhibitor PD98059. The p38-MAPK inhibitor abolished
      the butyrate effect on VDR expression and cell differentiation, while the ERK1/2
      inhibitor did not influence the butyrate-mediated induction of cell
      differentiation and VDR expression. The essential role of the p38 pathway in up
      regulation of VDR expression was further confirmed by using the p38 stimulator
      arsenite. These results imply an important role of the p38-MAPK in regulation of
      cellular differentiation through upregulation of VDR expression by butyrate.

PMID- 15504346
TI  - Crystal structure of human factor VIIa/tissue factor in complex with peptide
      mimetic inhibitor.
AB  - The 3D structure of human factor VIIa/soluble tissue factor in complex with a
      peptide mimetic inhibitor, propylsulfonamide-D-Thr-Met-p-aminobenzamidine, is
      determined by X-ray crystallography. As compared with the interactions between
      thrombin and thrombin inhibitors, the interactions at S2 and S3 sites
      characteristic of factor VIIa and factor VIIa inhibitors are revealed. The S2
      site has a small pocket, which is filled by the hydrophobic methionine side chain
      in P2. The small S3 site fits the small size residue, D-threonine in P3. The
      structural data and SAR data of the peptide mimetic inhibitor show that these
      interactions in the S2 and S3 sites play an important role for the improvement of
      selectivity versus thrombin. The results will provide valuable information for
      the structure-based drug design of specific inhibitors for FVIIa/TF.

PMID- 15504347
TI  - Identification of vasopressin-induced genes in AQP2-transfected MDCK cells by
      suppression subtractive hybridization.
AB  - Arginine vasopressin (AVP) plays a major role in the modulation of water
      reabsorption in mammalian kidney. In addition to short-term regulation of
      aquaporin 2 (AQP2) trafficking, AVP also has long-term effects to regulate the
      expression of AQP2 in renal collecting duct. However, the detailed mechanism of
      the long-term effects of AVP in kidney remains to be elucidated. We have searched
      for genes induced by AVP using the polymerase chain reaction-based suppression
      subtractive hybridization technique in AVP-responsive AQP2-transfected MDCK
      cells. We found that the expression of the genes such as VIP17/MAL, annexin II,
      stimulatory GTP binding protein, tubulin, and mitochondrial ATP synthase was
      induced by AVP treatment for 4h. These results suggest that AVP might induce the
      expression of several genes related to the apical targeting of newly synthesized
      AQP2 as well as that of AQP2 for the long-term modification of water permeability
      in renal collecting duct.

PMID- 15504348
TI  - Stimulation of the EAAT4 glutamate transporter by SGK protein kinase isoforms and
      PKB.
AB  - The serum and glucocorticoid inducible kinase (SGK) 1 is expressed in brain
      tissue and upregulated by ischemia, neuronal excitation, and dehydration. The
      present study has been performed to elucidate the expression of SGK1 in
      cerebellar Purkinje cells and to explore whether it influences the colocalized
      glutamate transporter EAAT4. Intense SGK1 staining was observed in Purkinje cells
      following 48h of water deprivation. The kinase activates glutamate induced
      current (I(GLU)) in Xenopus oocytes heterologously expressing EAAT4, an effect
      mimicked by its isoforms SGK2, 3 and PKB. I(GLU) was decreased by the ubiquitin
      ligase Nedd4-2, an effect partially but not completely reversed by additional
      coexpression of the SGK kinase isoforms or PKB. According to immunohistochemistry
      EAAT4 protein abundance in the cell membrane was enhanced by SGK1 and decreased
      by Nedd4-2. In conclusion, SGK1 expression is upregulated by ischemia,
      excitation, and dehydration in cerebellar Purkinje cells. The upregulation of
      SGK1 may serve to stimulate EAAT4 and thus to reduce neuroexcitotoxicity.

PMID- 15504349
TI  - Membrane-targeted peptides derived from Igalpha attenuate B-cell antigen receptor
      function.
AB  - Within the B-cell antigen receptor (BCR), heterodimers of Igalpha/Igbeta couple
      the receptor to intracellular signaling pathways. In the resting state, Igalpha
      associates with Src-family tyrosine kinases (SFTKs) which contain some basal
      activity. Upon engagement of the receptor, the SFTKs phosphorylate tyrosine
      residues in the BCR that recruit and activate the tyrosine kinase Syk, initiating
      signaling pathways. To test the hypothesis that disrupting the association
      between the resting receptor and the SFTKs would attenuate both basal and induced
      receptor activities, we expressed non-phosphorylatable membrane-targeted analogs
      of Igalpha (Igalpha/M) or Igbeta (Igbeta/M) in B lymphocytes. Both Igalpha/M and
      Igbeta/M inhibited BCR-induced calcium mobilization, but only Igalpha/M was able
      to diminish tyrosine phosphorylation. In an immature B-cell line, Igalpha/M
      attenuated both receptor-induced and basal apoptosis. Taken together, these data
      demonstrate the importance of the resting receptor complex and suggest
      therapeutic strategies for regulating receptor-mediated functions.

PMID- 15504350
TI  - Amblyomma americanum salivary gland homolog of nSec1 is essential for saliva
      protein secretion.
AB  - Soluble N-ethylmaleimide-sensitive factor attachment protein receptor proteins
      assemble in tight core complexes which promote fusion of carrier vesicles with
      target compartments. Members of this class of proteins are expressed in all
      eukaryotic cells and distributed in distinct subcellular compartments. All
      vesicle transport mechanisms known to date have an essential requirement for a
      member of the Sec1 protein family, including the nSec1 in regulated exocytosis. A
      homolog of nSec1 was cloned and sequenced from the salivary glands of partially
      fed female ticks. Double-stranded RNA was used to specifically reduce the amount
      of nSec1 mRNA and protein in female adult tick salivary glands. This reduction
      was accompanied by a decrease in anticoagulant protein release by the glands and
      by abnormalities in feeding by dsRNA treated ticks. We report the efficacy of
      double-stranded RNA-mediated interference in "knocking down" nSec1 both in vivo
      and in vitro in tick salivary glands and the applicability of this technique for
      studying the mechanism of exocytosis in tick salivary glands.

PMID- 15504351
TI  - Molecular dynamics of STAT3 on IL-6 signaling pathway in living cells.
AB  - Signal transducer and activator of transcription 3 (STAT3) is a critical signal
      transducer of interleukin-6 (IL-6) signaling. To investigate the mobility and the
      dynamics of STAT3 complex on IL-6 signaling in living cells, we generated a
      chimeric gene consisting of STAT3 fused to enhanced green fluorescence protein,
      STAT3-GFP. STAT3-GFP was expressed in Hep3B cells and the dynamics of this
      protein were analyzed by fluorescence correlation spectroscopy. After IL-6
      stimulation, STAT3 translocated from the cytoplasm to the nucleus, as shown
      previously. According to the analysis of STAT3 diffusion in stable transformants,
      the number of STAT3 molecules at the cytoplasmic membrane and in the cytoplasm
      decreased after IL-6 stimulation. In the nucleus, the diffusion speed of STAT3
      complex strongly decreased after IL-6 stimulation. Furthermore, we found that
      STAT3 existed as a complex whose molecular weight was less than 400kDa before IL
      6 addition. However, IL-6 stimulation induced the formation of STAT3 dimer as a
      megacomplex form whose molecular weight was more than 1MDa at the cytoplasm and a
      very slow diffusion complex in the nucleus.

PMID- 15504352
TI  - Full-length expanded ataxin-3 enhances mitochondrial-mediated cell death and
      decreases Bcl-2 expression in human neuroblastoma cells.
AB  - Machado-Joseph disease (MJD) is an autosomal dominant spinocerebellar
      degeneration characterized by a wide range of clinical manifestations. An
      unstable CAG trinucleotide repeat expansion in MJD gene on long arm of chromosome
      14 has been identified as the pathologic mutation of MJD and apoptosis was
      previously shown to be responsible for the neuronal cell death of the disease. In
      this study, we utilized human neuronal SK-N-SH cells stably transfected with HA
      tagged full-length MJD with 78 polyglutamine repeats to examine the effects of
      polyglutamine expansion on neuronal cell survival in the early stage of disease.
      Various pro-apoptotic agents were used to assess the tolerance of the mutant
      cells and to compare the differences between cells with and without mutant ataxin
      3. Concentration- and time-dependent experiments showed that the increase in
      staurosporine-induced cell death was more pronounced and accelerated in cells
      containing expanded ataxin-3 via MTS assays. Interestingly, under basal
      conditions, Western blot and immunocytochemical analyses showed a significant
      decrease of Bcl-2 protein expression and an increase of cytochrome c in cells
      containing expanded ataxin-3 when compared with those of the parental cells. The
      same reduction of Bcl-2 was further confirmed in fibroblast cells with mutant
      ataxin-3. In addition, exogenous expression of Bcl-2 desensitized SK-N-SH-MJD78
      cells to poly-Q toxicity. These results indicated that mitochondrial-mediated
      cell death plays a role in the pathogenesis of MJD. In our cellular model, full
      length expanded ataxin-3 that leads to neurodegenerative disorders significantly
      impaired the expression of Bcl-2 protein, which may be, at least in part,
      responsible for the weak tolerance to polyglutamine toxicity at the early stage
      of disease and ultimately resulted in an increase of stress-induced cell death
      upon apoptotic stress.

PMID- 15504353
TI  - Ahl3, a third locus on mouse chromosome 17 affecting age-related hearing loss.
AB  - Genetic variation in humans probably plays a role in determining the range of
      individual susceptibility to age-related hearing loss (AHL), but no contributing
      loci have been identified because of the difficulties of dissecting complex
      traits in humans. This paper reports mapping of an AHL locus using a panel of
      consomic mice between C57BL/6J (B6) and MSM strains, which covered more than a
      half of chromosome sets. B6 strain exhibited AHL beginning at 10 months of age
      whereas MSM strain, derived from Japanese wild mice, had normal hearing
      throughout life. Individuals in the panel were examined with auditory brainstem
      response (ABR) at various months of age, revealing that one particular strain (B6
      Chr17(MSM)) substituting the chromosome 17 with the MSM-derived one showed a
      prominent resistance, having still good hearing at 18 months of age. Subsequent
      mapping using 89 individuals in the cross between B6-Chr17(MSM) and B6 was
      performed, which showed a significant association of ABR thresholds with loci in
      the vicinity of D17Mit119. These results show a novel AHL-resistant locus,
      designated as Ahl3, on the chromosome 17.

PMID- 15504354
TI  - Acute and chronic hypoxic regulation of recombinant hNa(v)1.5 alpha subunits.
AB  - Acute and chronic hypoxic regulation of ion channels is involved in both cell
      physiology and pathology. Voltage-dependent Na(+) channels play a dominant role
      in the upstroke of the action potential in excitable cells, while non
      inactivating (persistent or sustained) Na(+) currents contribute to action
      potential shape and duration. In cardiac myocytes, hypoxic augmentation of
      persistent Na(+) currents has been proposed to underlie cardiac arrhythmias via
      prolonging action potential duration. Here, we demonstrate that acute hypoxia
      (P(O2), 20mm Hg) augmented persistent Na(+) currents in HEK293 cells stably
      expressing human Na(v)1.5 alpha subunits. Hypoxia also inhibited peak Na(+)
      currents in a voltage-dependent manner, and the kinetics of activation and
      inactivation of Na(+) currents were significantly slowed during hypoxia. We
      further demonstrate that exposure to chronic hypoxia (6% O(2) for 24h) augmented
      peak Na(+) channel current, which given the exogenous promoter driving expression
      of the channel occurs most probably via a post-transcriptional mechanism. These
      effects of acute and chronic hypoxia likely play an arrhythmogenic role during
      both short- and long-term hypoxic/ischaemic episodes. The HEK293 expression
      system provides a useful paradigm in which to examine the mechanisms of O(2)
      sensing by the Na(+) channel.

PMID- 15504355
TI  - Photoperiod-regulated expression of the PpCOL1 gene encoding a homolog of CO/COL
      proteins in the moss Physcomitrella patens.
AB  - The CONSTANS (CO) protein is a critical regulator of the photoperiodic control of
      flowering in Arabidopsis thaliana and Oryza sativa. We isolated a cDNA PpCOL1
      encoding a homolog of the CO/CO-LIKE (COL) family proteins from a cryptogam
      Physcomitrella patens. The predicted PpCOL1 protein has N-terminal zinc finger
      and C-terminal CCT domains, which are conserved in the angiosperm CO/COL
      proteins. Structurally, PpCOL1 is the most closely related to the Group Ia or Ic
      proteins, which include AtCO and AtCOL1/2, among diverged members of the family.
      A transient expression assay using GFP showed that the CCT domain of PpCOL1
      contains a nuclear-localizing signal. Northern blotting analyses revealed that
      the PpCOL1 expression is controlled by the circadian clock, and moreover, it is
      photoperiodically regulated at a gametophore stage when the rate of sporophyte
      formation is affected by day length. These observations indicate a possible
      involvement of PpCOL1 as a nuclear factor in the photoperiodic regulation of
      reproduction of Physcomitrella.

PMID- 15504356
TI  - Sp1 is involved in the transcriptional activation of lysozyme in epithelial
      cells.
AB  - Lysozyme protects us from the ever-present danger of bacterial infection. The
      expression of lysozyme is, in part, regulated by the Ets factor, myeloid elf-1
      like factor (MEF). MEF binds to the ETS site of the lysozyme promoter at -46 to 
      40bp. Closer analysis of the promoter using a series of deletion mutants and
      point mutants indicated that the region around -75bp is also essential in
      regulating the activity of lysozyme. The sequences in this region correspond to
      the Sp1 consensus binding site. Sp1 is known to regulate a variety of house
      keeping and tissue-specific genes by itself or with other transcription factors
      like AP-1 or ETS. We indicate here that Sp1 regulates the lysozyme gene by
      binding to the GT-core sequences of lysozyme promoter. Treatment with mithramycin
      A down-regulated the promoter activity and the transfection of anti-sense Sp1
      induced a decrease in the endogenous expression of lysozyme.

PMID- 15504357
TI  - Involvement of C/EBP-alpha gene in in vitro activation of rat hepatic stellate
      cells.
AB  - Hepatic stellate cells (HSCs) play key roles in hepatic fibrosis. One of the most
      striking alterations in activated HSCs is loss of cytoplasmic lipid droplets.
      However, the association of lipid storage with the activation of HSCs remains
      unclear. CCAAT/enhancer-binding proteins family (C/EBPs), especially C/EBP-alpha,
      controls differentiation of adipocytes. We suggested that C/EBP-alpha gene may be
      involved in HSCs activation. The present results showed that the expression
      levels of C/EBP-alpha and C/EBP-beta genes declined in activated HSCs. Over
      expression of C/EBP-alpha gene in activated HSCs: (1) inhibited HSCs
      proliferation, extracellular matrix-producing, alpha-smooth muscle actin gene
      expression, and induced rebound of cytoplasmic lipid droplets; (2) reduced
      retinoic acid receptor-beta, C/EBP-delta and -beta gene expressions, but
      increased the active form C/EBP-beta PSer(105), and induced retinoid X receptor
      alpha gene expression; and (3) did not affect the protein level of p16INK4a,
      p21Cip1/WAF1 or p27Kip1. In conclusions, C/EBP-alpha gene is involved in in vitro
      activation of rat HSCs.

PMID- 15504358
TI  - Cardiac abnormalities cause early lethality of jumonji mutant mice.
AB  - jumonji (jmj) mutant mice, obtained by a gene trap strategy, showed several
      morphological abnormalities including neural tube and cardiac defects, and died
      in utero around embryonic day 11.5 (E11.5). It is unknown what causes the
      embryonic lethality. Here, we demonstrate that exogenous expression of jmj gene
      in the heart of jmj mutant mice rescued the morphological phenotypes in the
      heart, and these embryos survived until E13.5. These results suggest that there
      are at least two lethal periods in jmj mutant mice, and that cardiac
      abnormalities may cause the earlier lethality. In addition, the rescue of the
      cardiac abnormalities by the jmj transgene provided solid evidence that the
      cardiac abnormalities resulted from mutation of the jmj gene.

PMID- 15504359
TI  - Molecular cloning and characterization of a human gene involved in
      transcriptional regulation of hTERT.
AB  - Human telomerase reverse transcriptase (hTERT), the catalytic subunit of
      telomerase in human, has been identified as the rate-limiting factor in
      telomerase activity, but its detailed mechanism of transcription regulation
      remains unclear. In this investigation, a novel human gene telomerase
      transcriptional elements-interacting factor (TEIF) was isolated from HeLa cell
      based on hTERT promoter yeast one-hybrid assay. TEIF has a 2358-bp open reading
      frame encoding a predicted protein of 786 amino acids, which is functionally
      conserved in general eukaryotic species. The transcription of TEIF was detected
      in cells and expressed an 86-kDa native protein, distributing mainly in cellular
      nuclei. Its interaction with hTERT promoter was identified and the DNA binding
      potential was credited to C-terminus of TEIF. Transfection of TEIF into HeLa
      cells presented marked transactivation of hTERT promoter and stimulated both
      endogenous hTERT transcription and telomerase activities. These results suggest
      that TEIF protein might be a transcription regulator and take part in the
      activation of hTERT.

PMID- 15504360
TI  - A regulatory role of Wnt signaling pathway in the hematopoietic differentiation
      of murine embryonic stem cells.
AB  - One of the most important issues in stem cell research is to understand the
      regulatory mechanisms responsible for their differentiation. An extensive
      understanding of mechanism underlying the process of differentiation is crucial
      in order to prompt stem cells to perform a particular function after
      differentiation. To elucidate the molecular mechanisms responsible for the
      hematopoietic differentiation of embryonic stem cells (ESCs), we investigated
      murine ES cells for the presence of hematopoietic lineage markers as well as Wnt
      signaling pathway during treatments with different cytokines alone or in
      combination with another. Here we report that Wnt/beta-catenin signaling is down
      regulated in hematopoietic differentiation of murine ES cells. We also found that
      differentiation induced by the interleukin-3, interleukin-6, and erythropoietin
      combinations resulted in high expression of CD3e, CD11b, CD45R/B220, Ly-6G, and
      TER-119 in differentiated ES cells. A high expression of beta-catenin was
      observed in two undifferentiated ES cell lines. Gene and protein expression
      analysis revealed that the members downstream of Wnt in this signaling pathway
      including beta-catenin, GSK-3beta, Axin, and TCF4 were significantly down
      regulated as ES cells differentiated into hematopoietic progenitors. Our results
      show that the Wnt/beta-catenin signaling pathway plays a role in the
      hematopoietic differentiation of murine ESCs and also may support beta-catenin as
      a crucial factor in the maintenance of ES cells in their undifferentiated state.

PMID- 15504361
TI  - Characterization of novel squamous cell carcinoma antigen-related molecules in
      mice.
AB  - The squamous cell carcinoma antigen 1 (SCCA1) and SCCA2 are unique serpins that
      can inhibit cysteine proteinases. SQN-5, their mouse ortholog, has already been
      identified, and its inhibitory property has been characterized; however, its
      biological role has remained undefined. Furthermore, no other mouse homolog of
      SQN-5 has been known. We characterize three mouse members of SCCA-related
      molecules including SQN-5 in this article. Serpinb3a (SQN-5) and Serpinb3b, but
      not Serpinb3c, were functional, inhibiting both serine and cysteine proteinases
      with different inhibitory profiles due to the difference of two amino acids in
      their reactive site loops. Serpinb3a was ubiquitously expressed in most tissues,
      whereas expression of Serpinb3b was limited to keratinocytes. Keratinocytes
      secreted both SCCA-related proteins, Serpinb3a and Serpinb3b. These results
      indicate that Serpinb3a and Serpinb3b may play different roles by inhibiting
      intrinsic or extrinsic proteinases with different expression distributions and
      different inhibitory profiles.

PMID- 15504362
TI  - The low molecular weight inhibitor of NCX1 interacts with a cytosolic domain that
      differs from the ion-transport site of the Na/Ca exchanger.
AB  - The endogenous inhibitory factor (NCX(IF)) of the cardiac Na/Ca exchanger (NCX1)
      is a low molecular weight substance, which has a strong capacity to modulate the
      ventricle muscle contractility. Previously, we have shown that NCX(IF) can
      completely inhibit either the forward (Na(i)-dependent Ca-uptake) or reverse
      (Na(o)-dependent Ca-release) mode of Na/Ca exchange as well as its partial
      reaction, the Ca/Ca exchange. Although the preliminary studies have shown that
      NCX(IF) can rapidly (within few milliseconds) interact with a putative inhibitory
      site of the Na/Ca exchanger protein (or within its vicinity), it was not clear
      whether the NCX(IF) can directly interact with the ion transport sites of the
      exchanger protein or the interaction site of NCX(IF) is distinct from the ion
      binding/transport site of NCX1. In order to segregate between these possibilities
      the NCX(IF) was tested for its capacity to compete with Ca at the cytosolic side
      by using the preparation of sarcolemma vesicles having predominantly the inside
      out orientation. For this goal, the initial rates of Na(i)-dependent (45)Ca
      uptake were measured in the presence of extravesicular (cytosolic) NCX(IF) under
      conditions in which the concentration of extravesicular Ca was varied (2-200
      microM) and intravesicular Na was kept fixed at saturating concentration (160
      mM). Under these conditions the NCX(IF) results in several fold decrease in
      V(max) values, while having no significant effect on the K(m). Taking into
      account the molecular weight of 350-550 Da (derived from the gel-filtration and
      mass-spectra data), the experimentally measured inhibitory potency of NCX(IF) can
      be estimated as the IC(50) = 0.3-0.6 microM. Therefore, it is concluded that the
      NCX(IF) is reasonably potent blocker, which interacts with cytosolic domain
      thereby preventing the ion-translocation (and not ion-binding) events.

PMID- 15504363
TI  - Alpha-synuclein has structural and functional similarities to small heat shock
      proteins.
AB  - The aggregation and fibrillization of alpha-synuclein, a major component of Lewy
      bodies, is a key event in Parkinson's disease. Although the mechanisms of fibrils
      formation are largely investigated, physiological function of alpha-synuclein is
      not yet clearly elucidated. Here, we showed that C-terminal region of alpha
      synuclein is similar to alpha-crystalline domain of small heat shock proteins. In
      our experiments, alpha-synuclein, like small heat shock proteins, protected
      cellular proteins from denaturation, and confer Escherichia coli cellular
      tolerances against thermal- and oxidative-stresses.

PMID- 15504364
TI  - Identification and characterization of a lymphocytic Rho-GTPase effector:
      rhotekin-2.
AB  - Rhotekin belongs to the group of proteins containing a Rho-binding domain that
      are target peptides (effectors) for the Rho-GTPases. We previously identified a
      novel cDNA with homology to human rhotekin and in this study we cloned and
      characterized the coding region of this novel 12-exon gene. The ORF encodes a 609
      amino-acid protein comprising a Class I Rho-binding domain and pleckstrin
      homology (PH) domain. Cellular cDNA expression of this new protein, designated
      Rhotekin-2 (RTKN2), was shown in the cytosol and nucleus of CHO cells. Using
      bioinformatics and RTPCR we identified three major splice variants, which vary in
      both the Rho-binding and PH domains. Real-time PCR studies showed exclusive RTKN2
      expression in pooled lymphocytes and further purification indicated sole
      expression in CD4(pos) T-cells and bone marrow-derived B-cells. Gene expression
      was increased in quiescent T-cells but negligible in activated proliferating
      cells. In malignant samples expression was absent in myeloid leukaemias, low in
      most B-cell malignancies and CD8(pos) T-cell malignancies, but very high in
      CD4(pos)/CD8(pos) T-lymphoblastic lymphoma. As the Rho family is critical in
      lymphocyte development and function, RTKN2 may play an important role in
      lymphopoiesis.

PMID- 15504365
TI  - Lithium modulation of the human inositol monophosphatase 2 (IMPA2) promoter.
AB  - The inositol-signaling pathway is a therapeutic target for lithium in the
      treatment of bipolar disorder. Inositol monophosphatases (IMPases) play a key
      role in inositol signaling. Lithium's ability to inhibit IMPase 1 is well known,
      but its effect on IMPase 2 or on the transcriptional regulation of these genes
      has not been studied. Here, we report the identification and characterization of
      the minimal promoter of IMPA2 (encoding IMPase 2) in HeLa (epithelial) and SK-N
      AS (neuronal) cells. IMPA2 promoter activity appears to be contributed by
      different elements in the 5' flanking region, suggesting that the gene is
      differentially regulated in neuronal and non-neuronal cells. Furthermore, IMPA2
      promoter activity in both cell lines is downregulated, in a dose-dependent
      manner, by lithium after treatment for only 24h. This effect is also observed in
      vivo. Our results suggest a possible role for IMPA2 in bipolar disorder.

PMID- 15504366
TI  - A selective requirement for copper-dependent activation of cytochrome c oxidase
      by Cox17p.
AB  - Cox17p is cloned from yeast as a chaperone to deliver copper to the mitochondria
      of assembly for cytochrome c oxidase (CCO). In mammals, CCO is a key enzyme for
      cellular respiration and a defect in its function is associated with severe
      neonatal or infantile lactic acidosis and early death. Recently, we found that
      Cox17p is not only required for mitochondrial oxidative phosphorylation but also
      is essential for embryonic growth and development in COX17 gene-deficient mice.
      To investigate its biochemical features, recombinant human Cox17p was
      overexpressed and purified without a purification tag. It specifically binds
      Cu(I) at a molar copper content of 3.3+/-0.04 under reduced conditions and
      significantly activates the mitochondrial CCO in vitro. Although the Cu-Cox17p
      complex was maintained between pH values from 5.0 to 7.7, Cu was completely
      released from Cox17p at pH 8.0. An acute exposure of excess amount of copper ion
      to mouse cells resulted in a significant reduction of Cox17p mRNA expression,
      whereas copper starvation maintained the Cox17p transcription level. These
      results suggest that the stringent selectivity of Cox17p for copper is required
      for CCO activation, to prevent copper overload, or promote the supply of copper.

PMID- 15504367
TI  - Molecular cloning, expression, and characterization of myo-inositol oxygenase
      from mouse, rat, and human kidney.
AB  - myo-Inositol oxygenase (MIOX) is a non-heme iron enzyme, which catalyzes the
      conversion of myo-inositol to d-glucuronic acid, the first committed step in myo
      inositol catabolism. Full-length cDNAs of 858bp each coding for 33kDa protein
      were cloned from kidney cDNA libraries of mouse, rat, and human. The individual
      clones were expressed in Escherichia coli and recombinant MIOX proteins were
      purified to electrophoretic homogeneity. A hydrophobic interaction chromatography
      step yielded multiple conformers, with mouse and human MIOX showing three peaks
      and rat enzyme revealing two peaks. Individual MIOX peaks exhibited distinct
      V(max) and K(m) values. Interestingly, upon storage, the 33kDa protein was
      degraded to a approximately 30kDa truncated protein in each species, and formed
      small amounts of dimers of identical subunits. While MIOX is a highly conserved
      enzyme in all mammalian species, the labile nature and tendency to degrade in
      solution may be the source of significant differences in size previously reported
      in the literature. Regardless of the source, our results strongly dispel previous
      conflicting literature reports on the size of the protein and confirm that MIOX
      is a 33kDa protein.

PMID- 15504368
TI  - Plasmodium vivax merozoite surface protein 8 cloning, expression, and
      characterisation.
AB  - Plasmodium vivax, one of the four parasite species causing malaria in humans, is
      the most widespread throughout the world, leading to nearly 80 million cases per
      year, mainly in Latin-America and Asia. An open reading frame encoding the
      Plasmodium falciparum merozoite surface protein 8 P. vivax homologue has been
      identified in the present study by screening the current data obtained from this
      parasite's partially sequenced genome. This new protein contains 487 amino-acids,
      two epidermal growth factor like domains, hydrophobic regions at the N- and C
      termini compatible with a signal peptide, and a glycosylphosphatidylinositol
      anchor site, respectively. This gene's transcription and its encoded protein
      expression have been assessed, as well as its recognition by P. vivax-infected
      patients' sera. Based on this recognition, and a previous study showing that mice
      immunised with the Plasmodium yoelii homologous protein were protected, we
      consider the PvMSP8 a good candidate to be included in a multi-stage multi
      antigen P. vivax vaccine.

PMID- 15504369
TI  - Involvement of ERK, a MAP kinase, in the production of TGF-beta by macrophages
      treated with liposomes composed of phosphatidylserine.
AB  - We have already reported that TGF-beta could be involved in the inhibitory
      effects of negatively charged liposomes composed of phosphatidylserine (PS
      liposome) on the production of nitric oxide (NO) by mouse peritoneal macrophages
      stimulated with LPS [Biochem. Biophys. Res. Commun. 281 (2001) 614]. In this
      paper, we explored the mechanism by which PS-liposomes promote the production of
      TGF-beta and the involvement of MAP kinases. When macrophages were treated with
      PS-liposomes, extracellular signal-regulated kinase (ERK), a member of MAP kinase
      superfamily, was activated quickly and potently. However, no activation was
      observed with p38 MAP kinase. TGF-beta production was completely inhibited by
      U0126, a specific inhibitor for ERK. Furthermore, TGF-beta neutralizing antibody
      and U0126 decreased the inhibitory effect of PS-liposomes on NO production by
      macrophages. These findings suggested that TGF-beta is the factor produced by PS
      liposomes that suppresses production of NO, and the ERK signaling pathway is
      intimately involved in TGF-beta production by macrophages following treatment
      with PS-liposomes.

PMID- 15504370
TI  - Inhibition of wortmannin activities by amino compounds.
AB  - Wortmannin caused normal and strong inhibition on catecholamine secretion from
      bovine adrenal chromaffin cells and in vitro phosphoinositide 3-kinase activity
      in NaCl-, Na isethionate-, choline Cl-, Na acetate-, and N-acetyl glycine-based
      media. However, brief preincubation of wortmannin with the media containing amino
      compounds such as glutamate, aspartate, lysine, and glycine resulted in the
      prevention of the inhibitory effects of wortmannin on the above responses as two
      indexes of wortmannin activities. On the other hand, the amino compounds also
      caused several rapid changes in wortmannin medium; the changes in absorption
      spectrum of the medium; and the changes in the retention time of the peak on the
      HPLC chromatogram using a reverse-phase C-18 column and in the pattern of
      absorption spectrum of the peak. These changes were not observed in the cases of
      NaCl, Na isethionate, choline Cl, Na acetate or N-acetyl glycine. Another amino
      compound Tris, which was commonly used as a pH buffer, was unique in time course
      and induced the slow but parallel changes and reached maximal up to about 24h.
      These results taken together indicate that the amino compounds markedly inhibit
      the activities of wortmannin presumably through the binding of wortmannin to
      amino group.

PMID- 15504371
TI  - Foxj1 regulates asymmetric gene expression during left-right axis patterning in
      mice.
AB  - Mice with a targeted mutation of the foxj1 gene demonstrate either D- or L
      looping of the embryonic cardiac tube. Foxj1 is expressed in ventral cells of the
      embryonic node prior to asymmetric, left-right expression of other genes. Despite
      an absence of 9+2 cilia in foxj1(-/-) mice, 9+0 cilia are present in the node of
      foxj1(-/-) embryos. In foxj1(-/-) embryos, the patterns of expression of the TGF
      beta family member nodal and the homeobox family member pitx2 are randomized. No
      expression of the TGF-beta family member lefty-2 is observed in any foxj1(-/-)
      early somite stage embryos. Foxj1 thus acts early in left-right axis patterning
      and regulates asymmetric gene expression. This regulation does not appear to be
      the result of a direct interaction between Foxj1 and the genes examined.

PMID- 15504372
TI  - Universal insurance coverage for contraceptives: a public health imperative.

PMID- 15504373
TI  - Women's and providers' attitudes toward menstrual suppression with extended use
      of oral contraceptives.
AB  - The United States Food and Drug Administration approved a dedicated extended
      regimen of oral contraceptive (OC) pill in the fall of 2003. Few studies have
      explored how women or providers feel about menstrual suppression. This study
      describes women's and providers' attitudes toward menstrual suppression. A
      national sample of 1470 women and 512 providers responded to surveys asking about
      attitudes toward menstrual suppression. Seventy-eight percent of the women sample
      had never heard of menstrual suppression with OCs. Fifty-nine percent of women
      would be interested in not menstruating every month and one third would choose
      never to have a period. Only 7% of the providers thought it was physically
      necessary to have a period every month and 44% thought that menstrual suppression
      is a good idea. While 57% of providers said that their patients do not ask about
      extended use of OCs, 52% do prescribe them; patient request was the most common
      reason. Both samples thought that more research should be conducted and that the
      factors that would influence their decisions included long-term health effects,
      side effects, future fertility and cost. Results demonstrate that providers need
      to discuss this option with their patients.

PMID- 15504374
TI  - Clinical and metabolic aspects of the continuous use of a contraceptive
      association of ethinyl estradiol (30 microg) and gestodene (75 microg).
AB  - This open, prospective, noncomparative study evaluated clinical and metabolic
      aspects of the use of a contraceptive combination of ethinyl estradiol (30
      microg) and gestodene (75 microg) continuously for 24 weeks in 45 women aged 25
      +/- 3.7 years. No alterations in weight or blood pressure were observed. Few side
      effects were recorded. Amenorrhea rates increased from the fourth month of
      observation onwards, reaching 81.2% by week 24. A reduction in the levels of
      cholesterol and LDL and an increase in HDL and triglycerides were observed.
      Insulin levels increased but not significantly, while levels of glycemia remained
      unchanged. Levels of antithrombin III, fibrinogen and plasminogen activator
      inhibitor-1 (PAI-1) increased, whereas a reduction was observed in proteins C and
      S and in prothrombin time (PT). Activated partial thromboplastin time (APTT)
      remained unchanged. The treatment was associated with satisfactory clinical
      effects, high rates of amenorrhea after the third treatment cycle, and resulted
      in metabolic changes similar to those encountered during the classic use of
      contraceptive pills with monthly interruption for withdrawal bleeding.

PMID- 15504375
TI  - Ovarian follicular development is initiated during the hormone-free interval of
      oral contraceptive use.
AB  - We evaluated ovarian follicular development in women during compliant use of oral
      contraceptives (OC). Thirty-six healthy women received: [35 microg ethinyl
      estradiol (21)/180 microg norgestimate (7), 215 microg norgestimate (7), 250
      microg norgestimate (7)]; [30 microg ethinyl estradiol (21)/150 microg
      desogestrel (21)]; or [20 microg ethinyl estradiol (21)/100 microg levonorgestrel
      (21)] for 3 consecutive 28-day cycles. Transvaginal ultrasonography was performed
      every third day to monitor follicular development. If a follicle reached > or =
      14 mm, ultrasonography was performed daily and blood drawn every other day to
      determine estradiol-17beta concentrations. Seventeen of 36 women (47%) grew
      follicles > or = 10 mm. Nine of the 17 women (53%) grew follicles > or = 14 mm,
      in association with increased serum concentrations of estradiol-17beta. Thirty
      seven of 43 follicles > or = 10 mm (86%) emerged during the hormone-free interval
      (HFI). No ovulations were observed. Our results supported the hypothesis that
      follicular development to an ostensibly ovulatory diameter occurs during
      compliant OC use, in association with loss of endocrine suppression during the
      HFI.

PMID- 15504376
TI  - Effect of etonogestrel subdermal contraceptive implant (Implanon) on liver
      function tests -- a randomized comparative study with Norplant implants.
AB  - OBJECTIVE: The study aimed to assess the possible differences in effects of
      Implanon and Norplant implants on liver function over 2 years of use. METHODS:
      This is a 2-year open randomized study of 80 implant (Implanon and Norplant)
      acceptors. Selected parameters of liver function were tested in the serum before
      implant insertion and at 6, 12 and 24 months after implant insertion. RESULTS: In
      both the implant groups, the mean total and unconjugated bilirubin and the gamma
      glutaryl transferase levels were significantly raised during implant use. For
      none of the subjects, at any sampling period, did the levels exceed the normal
      range in our population. There was no significant elevation of any other liver
      enzymes in either group. CONCLUSION: It appears that there may be mild
      hepatocellular dysfunction associated with the use of both Implanon and Norplant,
      which is possibly of no clinical significance to the healthy acceptor.

PMID- 15504377
TI  - Peripartum contraceptive attitudes and practices.
AB  - During pregnancy and the postpartum period, women may be more receptive to
      different methods of contraception for postpartum use. Few studies have focused
      on the peripartum population. In this study, currently pregnant and postpartum
      women were surveyed about their attitudes toward contraception, particularly in
      relation to the index pregnancy. Important contraceptive attributes for women
      included reliability, efficacy, and safety during breast-feeding, especially in
      the postpartum period. Over 80% of women surveyed were using contraception prior
      to pregnancy, but nearly 20% were not satisfied with the method used.
      Dissatisfaction with their method was more likely among women whose pregnancy was
      unplanned (36% vs. 9%). Over 40% of peripartum women indicated a desire to change
      their contraceptive after delivery. Sixty-five percent of women had received only
      limited information about intrauterine contraception before the survey. The
      results indicate that childbirth has a profound effect on contraceptive
      priorities and desires, especially toward long-term methods.

PMID- 15504378
TI  - Acceptability of home-use of misoprostol in medical abortion.
AB  - INTRODUCTION: Home-use of misoprostol would reduce the number of visits and
      improve access to medical abortion. We evaluated acceptance of home-use of
      misoprostol among women and their partners. MATERIALS AND METHODS: One hundred
      women with up to 49 days of amenorrhea were given mifepristone, followed by
      misoprostol taken at home. RESULTS: Women chose home-use of misoprostol because
      it felt more natural, private and allowed the presence of a partner/friend. Two
      women had a vacuum aspiration due to incomplete abortion. Five unscheduled visits
      occurred. Ninety-six women were satisfied with their choice of home-use. The male
      partners were generally satisfied with their partner's choice of home-use and
      felt that their presence and support had been valuable. DISCUSSION: Our study
      shows a high acceptability among women and their partners and confirms the safety
      and efficacy of home-use of misoprostol. Women should be offered this choice to
      allow more flexibility and privacy in their abortions.

PMID- 15504379
TI  - Medical versus surgical abortion efficacy, complications and leave of absence
      compared in a partly randomized study.
AB  - To provide optimal information to women choosing between early medical and
      surgical abortion, rigorous comparisons of the two methods are warranted. We
      compared the outcome of 1135 consecutive women with gestational age (GA) < or =
      63 days receiving either a medical (600 mg mifepristone and 1 mg gemeprost) or a
      surgical abortion (vacuum aspiration in general anesthesia). One hundred eleven
      of these women were randomized for abortion method. Surgical interventions and
      complications leading to readmission within the following 15 weeks were
      identified through a computer system. Information about antibiotic treatment,
      leave of absence and number of contacts to the health care system were obtained
      from mailed questionnaires. The number of complications was identical after the
      two methods, but surgical abortion was associated with a higher success rate
      [97.7% (708/725) vs. 94.1% (386/410), p < .01] and also with a higher risk of
      antibiotic treatment than medical abortion [7.8% (37/467) vs. 3.7% (13/356), p <
      .05]. The median leave of absence was shorter in women choosing a medical (1 day)
      than a surgical termination (2 days), p < .05. On average, one third of all the
      women requested at least one extra unscheduled consultation apart from a routine
      follow-up visit. We conclude that the chance of a primary successful termination
      at GA < or = 63 days is higher after a surgical abortion in general anesthesia
      compared to a medical abortion induced with 600 mg mifepristone and 1 mg
      gemeprost. A surgical abortion is associated with an increased risk of antibiotic
      treatment compared to medical abortion. The women's need for follow-up might be
      higher than we expect.

PMID- 15504380
TI  - Results and lessons learned from a small medical abortion clinical study in
      Turkey.
AB  - This article presents results from a small, introductory clinical study offering
      a simplified regimen medical abortion to women in Turkey. A total of 208 women
      from five sites were recruited from July 2000 through March 2001. All eligible
      consenting women were given 200 mg oral mifepristone at the clinic followed by
      400 microg oral misoprostol 2 days later either at home or at the clinic. The
      overall success rate of 84.1% is lower than in previous studies of this regimen,
      and a surprisingly high proportion of women (9.1%) were diagnosed with incomplete
      abortion. In spite of the higher than expected failure rate, women expressed a
      high degree of satisfaction. Several challenges were faced during this study,
      providing valuable insights about ways to introduce medical abortion into new
      settings with the best chances for success.

PMID- 15504381
TI  - Effectiveness of the male latex condom: combined results for three popular condom
      brands used as controls in randomized clinical trials.
AB  - BACKGROUND: Although public health programs invest heavily in the male latex
      condom, its efficacy in preventing pregnancy and sexually transmitted disease has
      been based primarily on in vitro and retrospective studies. METHODS: We combine
      the results from two randomized, controlled contraceptive efficacy trials that
      used commercial latex condoms brands (Ramses Sensitol, LifeStyles, Trojan-Enz) in
      the control arms. Combining data from the two studies, we obtained longitudinal
      data covering 3526 menstrual cycles contributed by approximately 800 couples who
      used latex condoms exclusively for up to six menstrual cycles. Both trials also
      collected 3715 detailed breakage and slippage reports from the first five study
      condom uses. The second trial also tested 243 postcoital vaginal samples
      collected after the first study condom use for the presence of prostate-specific
      antigen (PSA) and spermatazoa. RESULTS: The combined clinical breakage rate for
      the first five condom uses was 0.4% for the three latex brands and the combined
      clinical slippage rate was 1.1%. The combined six-cycle typical-use pregnancy
      rate for the latex condoms was 7.0% (95% confidence interval 5.0-9.0). The
      combined six-cycle consistent-use pregnancy rate was 1.0% (95% confidence
      interval 0.0-2.1). PSA was detected in only 1.2% of postcoital vaginal samples
      collected after the first use of an intact study condom. There were no
      differences in performance or efficacy among the three latex brands tested.
      CONCLUSIONS: The male latex condoms rarely broke or slipped off during
      intercourse and provided high contraceptive efficacy, especially when used
      consistently. Risk of semen leakage from intact condoms was very low.

PMID- 15504382
TI  - Contraception by Ushercell (cellulose sulfate) in formulation: duration of effect
      and dose effectiveness.
AB  - This study evaluated contraception by formulated Ushercell, a uniquely high
      molecular-weight form of cellulose sulfate, in the rabbit. Variables included (1)
      dose effectiveness, (2) duration of effectiveness, and (3) formulation
      excipients. Vaginally applied carboxymethyl-cellulose-based Ushercell gel is
      contraceptive. A 6% gel is active for at least 18 h; partial activity is observed
      for at least 24 h. With an application-insemination interval of 0.5 h, Ushercell
      as low as 0.1% is contraceptive. Contraception is incomplete with 2% Ushercell
      and an application-insemination interval of 24 h. Ushercell formulations
      containing a relatively high concentration of Carbopol are ineffective
      contraceptives, whether the gel is applied before insemination or is premixed
      with spermatozoa before insemination. Contraceptive activity is restored in
      Ushercell formulations with lower Carbopol content. This study shows that
      formulated Ushercell is an effective, long-lasting contraceptive and, hence, is
      bioavailable when vaginally applied. Activity is dependent on the type and
      relative concentration of formulation excipients. These data support a projected
      successful outcome of further clinical trials.

PMID- 15504383
TI  - Effect of glucomannan and the dosage form on ethinylestradiol oral absorption in
      rabbits.
AB  - To the beneficial properties of dietary fiber in human health, several
      disadvantages can be added as the possible modification of the bioavailability of
      other drugs when administered by the oral route. In this study, the influence of
      glucomannan in the oral bioavailability of ethinyl estradiol (EE), when
      administered to female rabbits in two different dosage forms (enteric capsules
      and dispersed in water), was established. To carry out the study, three groups of
      six animals each were used. All animals received 1 mg kg(-1) oral EE, and rabbits
      in groups 2 and 3 received 1.5 g glucomannan dispersed in water or in enteric
      capsules, respectively, immediately before EE. When comparing the results
      obtained after the administration of EE/glucomannan dispersed in water with those
      obtained after the administration of this estrogen without fiber, we can see that
      Cmax is 1.4 times lower, AUC 1.9 times lower and that tmax is identical (10 min).
      However, after the administration of fiber in enteric capsules, AUC and Cmax are
      higher (4.1 and 7.8 times, respectively) than when the estrogen was administered
      alone, and also, there is a delay in tmax (20 min). After the administration of
      glucomannan in the enteric capsule, the fiber forms, as in the stomach, a highly
      viscous solution in the gut that would limit EE access to the mucosal surface
      delaying its absorption. However, this effect could be compensated by a reduction
      of EE metabolism in the intestinal wall, leading to a higher absorption of the
      estrogen.

PMID- 15504384
TI  - Role of energy metabolism in the pregnancy interceptive action of Ferula
      assafoetida and Melia azedarach extracts in rat.
AB  - Ethanolic extract of Ferula assafoetida and chloroform fraction of Melia
      azedarach, both devoid of estrogenic activity, were examined for their pregnancy
      interceptive property. Treatment of rats from days 1 to 7 of pregnancy with
      either of the plant extracts resulted in pregnancy failure in about 65-85% of the
      animals. The possible role of energy metabolism in the antifertility action was
      investigated by measuring changes in activities of the key enzymes of
      carbohydrate metabolism in uterus on day 7 of pregnancy. It was observed that on
      the day 7 of pregnancy, one key enzyme of glycolytic pathway
      (phosphofructokinase) was significantly reduced in the uteri of treated rats as
      compared to controls. Hexosemonophosphate pathway also appeared to be sensitive
      to treatment with the plant extracts and showed an inhibitory effect on the
      enzyme activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate
      dehydrogenase. Oxidative energy metabolism through tricarboxylic acid cycle,
      which is considered to be the main source of energy to the uterus at this stage,
      was maximally affected by the treatment with several enzymes showing significant
      inhibition. The two plant materials appeared to interrupt the latter metabolic
      pathway more significantly. It is thus concluded that plants lacking
      phytoestrogens may intercept pregnancy by their ability to disrupt energy
      metabolism in rat uterus during implantation, especially the oxidative pathway.

PMID- 15504385
TI  - Implanon studies conducted in Indonesia.

PMID- 15504386
TI  - 2-[125I]-melatonin binding sites in the central nervous system and neural retina
      of the frog Rana perezi: regulation by light and temperature.
AB  - The objective of the present study is to test daily and seasonal changes in 2
      [125I]-Melatonin ([125I]-Mel) binding in different brain areas and the retina of
      the frog Rana perezi as well as the possible effect of light and temperature on
      melatonin receptors. During the day-night cycle, binding of [125I]-Mel showed a
      clear rhythm in the optic tectum, diencephalon, telencephalon, and neural retina,
      the binding being higher in the light phase than in the dark phase. By contrast,
      melatonin receptors did not show any significant summer-winter differences in any
      of the four tissues studied. In the neural retina, but not in the brain, exposure
      of frogs to 24 h darkness for one week leads to significantly less [125I]-Mel
      binding than 24 h light exposure. This darkness-induced reduction of [125I]-Mel
      binding is not due to a desensitisation of binding sites by high melatonin
      levels. Thermal acclimation to either 5 or 22 degrees C for one month did not
      change the affinity (Kd) and density (Bmax) of [125I]-Mel binding sites either in
      the brain or the retina. All these results indicate that there is a daily rhythm
      in melatonin receptors in the frog brain and retina, and that the light/dark
      cycle can drive this rhythm in [125I]-Mel binding in the retina. Temperature
      apparently did not modify [125I]-Mel binding in frogs.

PMID- 15504387
TI  - The influence of photoperiod on the reproductive activity of female Honey
      possums, Tarsipes rostratus (Marsupialia: Tarsipedidae): assessed by faecal
      progestagens and oestradiol-17beta.
AB  - Six female Honey possums were kept on a 15L:9D light regime to simulate a long
      daylength over summer. After seven weeks, three females (Group 2) were changed to
      a shorter daylength of 10L:14D, while the other three females (Group 1) were
      maintained on the long daylength. Faecal oestradiol-17beta and progestagen levels
      were measured during the experiment to detect any changes in reproductive rhythm,
      such as resumption of blastocyst development. Group 2 females were found to have
      very large and greatly expanded blastocysts with significantly higher levels of
      progestagens after the change to short photoperiod (p<0.05). In contrast, the
      Group 1 females had very small diapausing blastocysts and progestagen levels did
      not change throughout the study. Overall oestradiol levels also increased
      significantly in Group 2 females (p<0.05) but not in Group 1 females. These
      results demonstrate that a change from long to short days stimulates increased
      progestagen output (and oestradiol-17beta to a lesser extent) that supports the
      growth and expansion of the blastocysts. Photoperiod, in particular its change to
      a shortening daylength, appears to be a stimulus for terminating diapause in the
      Honey possum during its first reproduction of the year. However, as subsequent
      breeding later in the year occurs when daylength is increasing, a similar role
      for photoperiod cannot be attributed and females may be entrained to other
      factors such as food resources.

PMID- 15504388
TI  - Chicken growth hormone: further characterization and ontogenic changes of an N
      glycosylated isoform in the anterior pituitary gland.
AB  - Glycosylation is one of the post-translational modifications that growth hormone
      (GH) can undergo. This has been reported for human, rat, mouse, pig, chicken and
      buffalo GH. The nature and significance of GH glycosylation remains to be
      elucidated. This present study further characterizes glycosylated chicken GH (G
      cGH) and examines changes in the pituitary concentration of G-cGH during
      embryonic development and post hatching growth. G-cGH was purified from chicken
      pituitaries by affinity chromatography (Concanavalin A-Sepharose and monoclonal
      antibody bound to Sepharose). Immunoreactive G-cGH has a MW of 26 kDa or 29 kDa
      as determined by SDS-PAGE, respectively, under non-reducing and reducing
      conditions. Evidence that it is N-glycosylated comes from its susceptibility to
      peptide N-glycosidase F, and its resistance to O-glycosidase. Based on the
      ability of G-cGH to bind Concanavalin A or wheat germ agglutinin but not other
      lectins and its susceptibility to peptide N-glycosidase F, a hybrid or
      biantennary type glycopeptide (GlcNac2, Man) structure is proposed. Some G-cGH
      can be observed in the pituitary at most ages examined (from 15-day embryo to
      adult). Moreover, electron microscopy revealed the presence of both immuno
      reactive GH and Concanavalin A-reactive sites in the same secretory granules in
      the somatotrope. There were marked changes in the level and relative proportion
      of G-cGH in the pituitary gland during development and growth, the proportion of
      G-cGH rising during late embryonic development (e.g., between 15 and 18 days of
      development) and with further increases between 9 weeks and 15 weeks old. G-cGH
      was able to bind to chicken liver membrane preparations with less affinity than
      non-glycosylated monomer; on the other hand, however, G-cGH stimulated cell
      proliferation on Nb2 lymphoma bioassay whereas the non-glycosylated monomer was
      uncapable to do it.

PMID- 15504389
TI  - Excremental androgen metabolite concentrations and gonad sizes in temperate zone
      vs. tropical Stonechats (Saxicola torquata ssp.).
AB  - Many songbirds in the temperate zones have comparatively short breeding seasons
      and are migratory. This often implies high breeding synchrony and competition for
      food, space, and mates. Tropical birds, in contrast, tend to be resident and
      react more flexibly to a more variable onset of environmental conditions
      conducive for breeding. Therefore, it can be expected that androgen metabolite
      concentrations in breeding males vary among birds from different latitudes.
      Studies on tropical birds, however, have revealed inconsistent results suggesting
      that additional factors not directly related to latitude, modify hormone levels.
      Furthermore, there is a potential for a phylogenetic bias when comparing birds of
      different taxonomic groups. In the present study, we compared androgen metabolite
      concentrations among closely related taxa of hand-raised male stonechats
      originating from tropical and temperate-zone populations in Kenya (0 degrees
      latitude), Kazakhstan (52 degrees N), and Ireland (52 degrees N), which differ
      partly in latitude of their provenance but also in the length of their breeding
      season (birds from Kazakhstan vs. Ireland). Hand-raised birds were housed in
      their natural photoperiod under otherwise identical environmental conditions.
      Androgen levels were determined from excrements to reduce disturbance. All three
      groups demonstrated a seasonal cycle of androgen metabolite concentrations
      concomitant with testis growth. Peak androgen metabolite concentrations were
      significantly lower in Kenyan stonechats compared to Kazakh stonechats. Irish
      birds had intermediate concentrations. Differences between Kazakh and Kenyan
      stonechats correlate with latitude, but data from the Irish population suggest
      the involvement of factors not directly related to latitude.

PMID- 15504390
TI  - Changes in mRNA expression of MMP-2 in the Mullerian duct of chicken embryo.
AB  - Although asymmetric development of the ovary and the oviduct is a unique
      characteristic in birds, the mechanism of asymmetric development still remains
      unclear. Recently, degradation of extracellular matrix has been suggested as an
      important factor related to the regression of the Mullerian duct in mammals. The
      present study was conducted to examine a possible role of metalloproteinase-2
      (MMP-2) in the regression of the right Mullerian duct in the developing chicken
      embryo. Morphological changes in the Mullerian ducts were studied on day 15 of
      incubation and mRNA expresseion of MMP-2 was studied on days 12, 15, and 18 of
      incubation. Morphological observation demonstrated the disappearance of basement
      membrane in the right Mullerian duct which undergoes the regression. RT-PCR
      analysis showed that MMP-2 mRNA expression of the right Mullerian duct increased
      on days 15 and 18 of incubation coincidently with the time of regression. In the
      right Mullerian duct, regression was prevented by diethylstilbestrol treatment on
      day 4 of incubation and a coincident decrease in MMP-2 expression was observed
      when compared to the control group. These results suggest that MMP-2 may be
      involved in the regression of the right Mullerian duct in the female embryos of
      the chicken.

PMID- 15504392
TI  - Reproductive cycle of the Neotropical Crotalus durissus terrificus: I. Seasonal
      levels and interplay between steroid hormones and vasotocinase.
AB  - Crotaline snakes present delayed fertilization and sperm storage because
      secondary vitellogenesis is not completed by the time of mating. The release of
      vitellogenesis and synchrony between ovulation and fertilization suggest a
      steroidal modulation. We investigated changes of sexual steroid levels during
      reproduction in the Neotropical rattlesnake Crotalus durissus terrificus,
      analyzing macroscopical variations of reproductive condition (vitellogenesis,
      pregnancy, and post-partum) and plasma levels of estradiol, progesterone, and
      vasotocinase cystine aminopeptidase (CAP) activity over 2 years. Data showed
      44.4% non-reproductive snakes (40.1% primary vitellogenesis and 4.3% post-partum)
      and 55.6% reproductive (36.8% secondary vitellogenesis and 18.8% pregnant).
      Estradiol was low in spring and summer, increasing in autumn till it peaked in
      winter. Estradiol in secondary vitellogenesis was significantly higher than in
      primary vitellogenesis, or in pregnant and post-partum females, Progesterone
      dropped significantly in autumn compared to summer, winter, and spring. Pregnant
      females showed the highest levels of progesterone compared to primary or
      secondary vitellogenesis, or post-partum females. CAP activity showed lowest
      values in reproductive females in autumn and greatest levels in post-partum
      females. A significant negative linear relationship was obtained between CAP
      activity and estradiol. The combination of morphological observations, levels of
      steroids and CAP activity allowed us to suggest a similar morphological
      reproductive pattern between temperate and tropical rattlesnakes, and to infer
      the role of estradiol, progesterone and CAP activity on vitellogenesis, gestation
      and sperm storage, respectively.

PMID- 15504391
TI  - Serum leptin concentration during the terrestrial phase of the Southern elephant
      seal Mirounga leonina (Carnivora: Phocidae).
AB  - This study aimed to verify the serum leptin concentration during the terrestrial
      phase of the Southern elephant seal (Mirounga leonina) on Elephant Island (South
      Shetlands, Antarctica). Sera from 25 adult Southern elephant seals were analyzed.
      Leptin concentration was determined using the 125I radioimmunoassay method. Total
      protein, triglycerides, and cholesterol concentration were measured by
      spectrophotometric methods. Seals were grouped by sex and their physiological
      status (reproducing or molting seals). In reproducing seals, serum concentrations
      of leptin, total protein, triglycerides, and cholesterol were, respectively,
      9.33+/-1.97 ng/ml, 6.87+/-0.09 g/dl, 98.26+/-2.12 mg/dl, and 232.17+/-41.18 mg/dl
      in males and 5.30+/-1.36 ng/ml, 6.44+/-0.29 g/dl, 109.01+/-3.34 mg/dl, and
      219.20+/-26.65 in females (mean+/-1 SD). In molting seals, these values were
      2.35+/-1.51 ng/ml, 7.42+/-0.25 mg/dl, 321.10+/-20.01 mg/dl, and 244.66+/-22.24
      mg/dl in males and 2.94+/-1.89 ng/ml, 7.88+/-0.46 mg/dl, 197.54 mg/dl, and
      224.55+/-16.70 mg/dl in females. In both males and females, there were no
      significant differences (P>0.05) in total protein and cholesterol concentration
      between reproducing and molting seals. However, both males and females showed
      higher leptin concentration (P<0.05) and lower triglyceride concentration
      (P<0.05) in the reproductive period than in the molt period. In the reproductive
      period, it was expected that the Southern elephant seal shows an inhibited hunger
      sensation, mobilizes stored energy, and stimulates the HPG axis. Results from the
      present study support this hypothesis and suggest that this strategy may be
      effected by the hormonal stimulation of leptin.

PMID- 15504393
TI  - Reproductive cycle of the Neotropical Crotalus durissus terrificus: II.
      Establishment and maintenance of the uterine muscular twisting, a strategy for
      long-term sperm storage.
AB  - Crotaline snakes store sperm by means of a uterine musculature twisting (UMT). We
      investigated the influence of plasma levels of estradiol and progesterone and
      vasotocinase cystine aminopeptidase (CAP) activity on UMT formation and
      maintenance, and the in vitro uterine reactivity for AVT in Crotalus durissus
      terrificus in primary or secondary vitellogenesis with or without UMT. Frequency
      of females in secondary vitellogenesis with UMT is significantly higher than in
      primary one. Estradiol levels did not vary in all conditions studied, however,
      significantly low levels of progesterone were found in snakes in secondary
      vitellogenesis with UMT compared to those without it. UMT is always observed when
      high levels of estradiol and low levels of progesterone are detected. CAP
      activity did not change in the presence of UMT. AVT produced concentration
      response contractions of the isolated uterus of snakes in all stages analysed and
      the pD2 value and maximum contractile response were significantly higher in
      primary vitellogenesis without UMT than in other reproductive conditions,
      indicating that uterus of those snakes presents a higher contractile capacity
      which may favour UMT establishment. In conclusion, we show a relationship of UMT
      and estradiol/progesterone balance and a possible participation of AVT in UMT
      formation and maintenance in the Neotropical rattlesnake.

PMID- 15504394
TI  - Testicular growth hormone (GH): GH expression in spermatogonia and primary
      spermatocytes.
AB  - Growth hormone (GH) gene expression is not restricted to pituitary somatotrophs
      and has recently been demonstrated in a variety of extrapituitary sites in
      mammals and the domestic chicken. The possibility that GH gene expression occurs
      in the male reproductive system of chickens was therefore examined, since GH has
      established roles in male reproductive function and GH immunoreactivity is
      present in the chicken testis. Using RT-PCR and oligonucleotide primers for
      pituitary GH cDNA, GH mRNA was shown to be present in the testes and vas deferens
      of adult cockerels. Although testicular GH mRNA was of low abundance (not
      detectable by Northern blotting), a 690 bp fragment of the amplified testicular
      GH cDNA was cloned and had a nucleotide sequence 99.6% homologous with pituitary
      GH cDNA. GH mRNA was localized by in situ hybridization in spermatogonia and
      primary spermatocytes of the seminiferous tubules, but unlike testicular GH
      immunoreactivity, GH mRNA was not present in secondary spermatocytes, spermatids
      or spermatozoa. The presence of Pit-1 mRNA in the male reproductive tract may
      indicate Pit-1 involvement in GH expression in these tissues. The presence of GH
      receptor mRNA in the testis and vas deferens also suggests they are target sites
      for GH action. These results demonstrate, for the first time, expression of the
      pituitary GH gene in the testis, in which GH mRNA was discretely localized in
      primary spermatocytes. The local expression of the GH gene in these cells
      suggests autocrine or paracrine actions of GH during spermatogenesis.

PMID- 15504395
TI  - Testicular FGF-1 protein is involved in Sertoli cell-spermatid interaction in roe
      deer.
AB  - Roe deer (Capreolus capreolus) is a seasonal breeder showing extreme changes in
      spermatogenic activity. It is an excellent model to study the regulation of
      testicular activation and regression by endocrine signals and paracrine effectors
      such as growth factors. Previous studies on FGF-1 mRNA showed a special seasonal
      expression pattern in roe deer testis. This was difficult to explain by their
      exclusive localization in interstitial and Sertoli cells and without detection of
      the translation product. Therefore, the cellular localization of the FGF-1
      protein was studied during a complete annual cycle. Parenchyma samples were
      collected bimonthly and prepared for histological and immunohistochemical
      investigations. A polyclonal rabbit anti-bovine FGF-1 antibody was used for
      indirect immunohistochemistry. Seasonal changes in the cellular composition of
      roe deer testis parenchyma were quantified by morphometry and means of computer
      aided image analysis. In the tubular compartment FGF-1 protein was exclusively
      (and stage-specific) present in elongating spermatids. This cell type occurs
      shortly before (June) and during the rutting season (August) only. In
      interstitial cells FGF-1 is detectable throughout the whole year. Results suggest
      FGF-1 being involved in Sertoli cell-spermatid communication and could also serve
      as a survival factor for somatic cell populations within the testis. The
      occurrence of the protein indicates an increased expression of this factor during
      activated spermatogenesis.

PMID- 15504396
TI  - New insights into the evolution of the GRF superfamily based on sequence
      similarity between the locust APRPs and human GRF.
AB  - In a manual sequence alignment experiment we accidentally observed that the
      locust adipokinetic hormone (AKH) precursor-related peptides (APRPs), which are
      peptides contained in the AKH-preprohormones, display sequence similarity with
      human growth hormone-releasing factor (GRF). So far, a counterpart for GRF,
      either structurally or functionally, has not yet been reported in any non
      chordate. This could give new insights into the origin of the GRF superfamily, as
      it would mean that in some invertebrates (locusts), the structural homologues of
      glucagons (AKHs) and GRFs (APRPs) are located on the same precursor. No function
      could as yet be attributed to APRPs, although these neuropeptides occur
      abundantly in the corpora cardiaca, a neurohaemal organ from which many
      neuropeptides are released. Therefore, similar to GRF, a role as releasing factor
      may be envisaged for APRPs.

PMID- 15504397
TI  - Characterization of biologically active bovine pituitary FSH purified by
      immunoaffinity chromatography using a monoclonal antibody.
AB  - A substantial amount of highly purified, biologically active bovine FSH was
      isolated from pituitary extracts by immunoaffinity chromatography based on a
      novel anti-bovine FSH beta-subunit monoclonal antibody. The biological activity
      was assessed in vitro using a steroidogenic granulosa cell line constitutively
      expressing the FSH receptor. Amino acid analysis, N-terminal amino acid
      sequencing, and peptide mass mapping demonstrated that primary structure
      modifications do not contribute to the heterogeneity of bovine FSH. The
      monosaccharide composition of the N-linked oligosaccharides was quantified and
      remarkably two distinct forms of sialic acids, N-acetyl- and N-glycolyl
      neuraminic acids were found. In conclusion, we showed that isoform differences in
      bovine FSH is likely due only to sugar chain heterogeneity, and we give the first
      evidence that two substituted sialic acids contribute to the diversity of
      mammalian glycoprotein hormone isoforms.

PMID- 15504398
TI  - Genetic evidence for pre-recruitment as the mechanism of transcription activation
      by SoxS of Escherichia coli: the dominance of DNA binding mutations of SoxS.
AB  - SoxS, the direct transcriptional activator of the Escherichia coli superoxide
      (SoxRS) regulon, displays several unusual characteristics which suggest that it
      is unlikely to activate transcription by the ususal recruitment mechanism. Thus,
      agents that generate superoxide endogenously and thereby provoke the defense
      response elicit the de novo synthesis of SoxS, and with the SoxS binding site
      being highly degenerate, the number of SoxS binding sites per cell far exceeds
      the number of SoxS molecules per cell. To account for these distinctive features
      of the SoxRS system, we proposed "pre-recruitment" as the mechanism by which SoxS
      activates transcription of the regulon's genes. In pre-recruitment, newly
      synthesized SoxS molecules form binary complexes with RNA polymerase in solution.
      These complexes provide the information content to allow the 2500 molecules of
      SoxS per cell to scan the 65,000 SoxS binding sites per cell for the 200 binding
      sites per cell that reside within SoxS-dependent promoters. As a test of whether
      SoxS activates transcription by recruitment or pre-recruitment, we determined the
      dominance relationships of SoxS mutations conferring defective DNA binding. We
      found that soxS DNA binding mutations are dominant to the wild-type allele, a
      result consistent with the pre-recruitment hypothesis, but opposite to that
      expected for an activator that functions by recruitment. Moreover, whereas
      positive control mutations of activators functioning by recruitment are usually
      dominant, a soxS positive control mutation was not. Lastly, with the SoxRS system
      as an example, we discuss the physiological requirement for stringent regulation
      of transcriptional activators that function by pre-recruitment.

PMID- 15504399
TI  - Anti-termination by SIV Tat requires flexibility of the nascent TAR structure.
AB  - Substitution of the SIVmac239 promoter/enhancer by the strong EF1alpha promoter
      results in a severe replication defect due to a failure to respond to Tat.
      Revertant viruses with minimal promoter sequences (two Sp1 sites and a TATA box)
      were obtained that had fully restored their replicative potential. Comparison of
      the different LTRs indicated that structural alterations in the TAR stem due to a
      31bp exon of the EF1alpha promoter rather than the mere presence of transcription
      factor binding sites within U3 were responsible for the attenuation. Structural
      models based on genuine RNA sequences combined with a refined algorithm to
      calculate the probability of the looping-mediated interaction between protein
      complexes bound to nucleic acid polymers indicated that the local concentration
      of TAR-bound Tat close to the RNA polymerase II complex was reduced more than 100
      fold for the mutant as compared to SIVmac239. These results show that HIV/SIV
      replication requires only a minimal set of cis-acting elements in the promoter
      and suggest a hitherto unrecognised requirement of flexibility for the nascent
      TAR structure to allow anti-termination by Tat.

PMID- 15504400
TI  - All-atom Monte Carlo simulation of GCAA RNA folding.
AB  - We report a detailed all-atom simulation of the folding of the GCAA RNA
      tetraloop. The GCAA tetraloop motif is a very common and thermodynamically stable
      secondary structure in natural RNAs. We use our simulation methods to study the
      folding behavior of a 12-base GCAA tetraloop structure with a four-base helix
      adjacent to the tetraloop proper. We implement an all-atom Monte Carlo (MC)
      simulation of RNA structural dynamics using a Go potential. Molecular dynamics
      (MD) simulation of RNA and protein has realistic energetics and sterics, but is
      extremely expensive in terms of computational time. By coarsely treating non
      covalent energetics, but retaining all-atom sterics and entropic effects, all
      atom MC techniques are a useful method for the study of protein and now RNA. We
      observe a sharp folding transition for this structure, and in simulations at room
      temperature the state histogram shows three distinct minima: an unfolded state
      (U), a more narrow intermediated state (I), and a narrow folded state (F). The
      intermediate consists primarily of structures with the GCAA loop and some helix
      hydrogen bonds formed. Repeated kinetic folding simulations reveal that the
      number of helix base-pairs forms a simple 1D reaction coordinate for the I-->N
      transition.

PMID- 15504401
TI  - Theory of nucleosome corkscrew sliding in the presence of synthetic DNA ligands.
AB  - Histone octamers show a heat-induced mobility along DNA. Recent theoretical
      studies have established two mechanisms that are qualitatively and quantitatively
      compatible with in vitro experiments on nucleosome sliding: octamer repositioning
      through one-base-pair twist defects and through ten-base-pair bulge defects. A
      recent experiment demonstrated that the repositioning is strongly suppressed in
      the presence of minor-groove binding DNA ligands. In the present study, we give a
      quantitative theory for nucleosome repositioning in the presence of such ligands.
      We show that the experimentally observed octamer mobilities are consistent with
      the picture of bound ligands blocking the passage of twist defects through the
      nucleosome. This strongly supports the model of twist defects inducing a
      corkscrew motion of the nucleosome as the underlying mechanism of nucleosome
      sliding. We provide a theoretical estimate of the nucleosomal mobility without
      adjustable parameters, as a function of ligand concentration, binding affinity,
      binding site orientation, temperature and DNA anisotropy. Having this mobility in
      hand, we speculate on the interaction between a nucleosome and a transcribing RNA
      polymerase, and suggest a novel mechanism that might account for polymerase
      induced nucleosome repositioning on short DNA templates.

PMID- 15504402
TI  - A simple physical model for the prediction and design of protein-DNA
      interactions.
AB  - Protein-DNA interactions are crucial for many biological processes. Attempts to
      model these interactions have generally taken the form of amino acid-base
      recognition codes or purely sequence-based profile methods, which depend on the
      availability of extensive sequence and structural information for specific
      structural families, neglect side-chain conformational variability, and lack
      generality beyond the structural family used to train the model. Here, we take
      advantage of recent advances in rotamer-based protein design and the large number
      of structurally characterized protein-DNA complexes to develop and parameterize a
      simple physical model for protein-DNA interactions. The model shows considerable
      promise for redesigning amino acids at protein-DNA interfaces, as design
      calculations recover the amino acid residue identities and conformations at these
      interfaces with accuracies comparable to sequence recovery in globular proteins.
      The model shows promise also for predicting DNA-binding specificity for fixed
      protein sequences: native DNA sequences are selected correctly from pools of
      competing DNA substrates; however, incorporation of backbone movement will likely
      be required to improve performance in homology modeling applications.
      Interestingly, optimization of zinc finger protein amino acid sequences for high
      affinity binding to specific DNA sequences results in proteins with little or no
      predicted specificity, suggesting that naturally occurring DNA-binding proteins
      are optimized for specificity rather than affinity. When combined with algorithms
      that optimize specificity directly, the simple computational model developed here
      should be useful for the engineering of proteins with novel DNA-binding
      specificities.

PMID- 15504403
TI  - The N-terminal alpha-helix of pancreatic phospholipase A2 determines productive
      mode orientation of the enzyme at the membrane surface.
AB  - Phospholipase A(2) (PLA(2)) hydrolyzes glycerophospholipids to free fatty acid
      and lyso-phospholipid, which serve as precursors for the biosynthesis of
      eicosanoids and other lipid-derived mediators of inflammation and allergy. PLA(2)
      activity strongly increases upon binding to the surface of aggregated
      phospholipid. The N-terminal approximately ten residue alpha-helix of certain
      PLA(2) isoforms plays important roles in the interfacial activation of the enzyme
      by providing residues for membrane binding of PLA(2) and by contributing to the
      formation of the substrate-binding pocket. However, the relative contributions of
      the N-terminal alpha-helix and the rest of the protein in membrane binding of
      PLA(2) and its productive-mode orientation at the membrane surface are not well
      understood. Here we use a variety of biophysical approaches to determine the role
      of the N-terminal helix in membrane binding strength, orientation, and activity
      of human pancreatic PLA(2). While the full-length PLA(2) binds to membranes with
      a defined orientation, an engineered PLA(2) fragment DeltaN10 that lacks the N
      terminal ten residues binds to membranes with weaker affinity and at random
      orientation, and exhibits approximately 100-fold lower enzymatic activity
      compared to the full-length PLA(2), indicating the key role of the N terminus in
      PLA(2) function. The results of polarized infrared spectroscopic experiments
      permit determination of the orientation of membrane-bound PLA(2) and
      identification of its interfacial binding surface. Moreover, the full-length
      PLA(2) demonstrates increased conformational flexibility in solution and is
      stabilized upon membrane binding, while the DeltaN10 fragment is more rigid than
      the full-length PLA(2) both in free and membrane-bound states. Our results
      suggest that the N-terminal alpha-helix supports the activation of PLA(2) by (a)
      enhancing the membrane binding strength, (b) facilitating a productive-mode
      orientation of PLA(2) at the membrane surface, and (c) conferring conformational
      integrity and plasticity to the enzyme.

PMID- 15504404
TI  - Cryoelectron microscopy imaging of recombinant and tissue derived vaults:
      localization of the MVP N termini and VPARP.
AB  - The vault is a highly conserved ribonucleoprotein particle found in all higher
      eukaryotes. It has a barrel-shaped structure and is composed of the major vault
      protein (MVP); vault poly(ADP-ribose) polymerase (VPARP); telomerase-associated
      protein 1 (TEP1); and small untranslated RNA (vRNA). Although its strong
      conservation and high abundance indicate an important cellular role, the function
      of the vault is unknown. In humans, vaults have been implicated in multidrug
      resistance during chemotherapy. Recently, assembly of recombinant vaults has been
      established in insect cells expressing only MVP. Here, we demonstrate that co
      expression of MVP with one or both of the other two vault proteins results in
      their co-assembly into regularly shaped vaults. Particles assembled from MVP with
      N-terminal peptide tags of various length are compared. Cryoelectron microscopy
      (cryoEM) and single-particle image reconstruction methods were used to determine
      the structure of nine recombinant vaults of various composition, as well as wild
      type and TEP1-deficient mouse vaults. Recombinant vaults with MVP N-terminal
      peptide tags showed internal density that varied in size with the length of the
      tag. Reconstruction of a recombinant vault with a cysteine-rich tag revealed 48
      fold rotational symmetry for the vault. A model is proposed for the organization
      of MVP within the vault with all of the MVP N termini interacting non-covalently
      at the vault midsection and 48 copies of MVP forming each half vault. CryoEM
      difference mapping localized VPARP to three density bands lining the inner
      surface of the vault. Difference maps designed to localize TEP1 showed only weak
      density inside of the caps, suggesting that TEP1 may interact with MVP via a
      small interaction region. In the absence of atomic-resolution structures for
      either VPARP or TEP1, fold recognition methods were applied. A total of 21
      repeats were predicted for the TEP1 WD-repeat domain, suggesting an unusually
      large beta-propeller fold.

PMID- 15504405
TI  - Folding mechanism of the CH2 antibody domain.
AB  - The immunoglobulin C(H)2 domain is a simple model system suitable for the study
      of the folding of all-beta-proteins. Its structure consists of two beta-sheets
      forming a greek-key beta-barrel, which is stabilized by an internal disulfide
      bridge located in the hydrophobic core. Crystal structures of various antibodies
      suggest that the C(H)2 domains of the two heavy chains interact with their sugar
      moieties and form a homodimer. Here, we show that the isolated, unglycosylated
      C(H)2 domain is a monomeric protein. Equilibrium unfolding was a two-state
      process, and the conformational stability is remarkably low compared to other
      antibody domains. Folding kinetics of C(H)2 were found to consist of several
      phases. The reactions could be mapped to three parallel pathways, two of which
      are generated by prolyl isomerizations in the unfolded state. The slowest folding
      reaction, which was observed only after long-term denaturation, could be
      catalyzed by a prolyl isomerase. The majority of the unfolded molecules, however,
      folded more rapidly, on a time-scale of minutes. Presumably, these molecules also
      have to undergo prolyl isomerization before reaching the native state. In
      addition, we detected a small number of fast-folding molecules in which all
      proline residues appear to be in the correct conformation. On both prolyl
      isomerization limited pathways, the formation of partly structured intermediates
      could be observed.

PMID- 15504406
TI  - Crystal structure of the hemoglobin dodecamer from Lumbricus erythrocruorin:
      allosteric core of giant annelid respiratory complexes.
AB  - Erythrocruorins are highly cooperative giant extracellular respiratory complexes
      found in annelids, where they serve the same function as red blood cells. Our
      previous 5.5A resolution crystal structure of Lumbricus terrestris erythrocruorin
      revealed a hierarchical organization of 144 oxygen-binding hemoglobin chains that
      are assembled into 12 dodecamers arranged at the periphery of the complex around
      a central scaffold formed by 36 non-hemoglobin subunits. We present here the 2.6A
      resolution crystal structure of the Lumbricus hemoglobin dodecameric subassembly,
      which provides the first atomic models of the erythrocruorin allosteric core. The
      hemoglobin dodecamer has a molecular 3-fold axis of symmetry that relates three
      heterotetramers, each of which is composed of two tightly associated
      heterodimers. The structure reveals details of the interfaces, including key side
      chain interactions likely to contribute to ligand-linked allosteric transitions,
      and shows the crowded nature of the ligand-binding pockets. Comparison of the
      Lumbricus dimeric assemblies with similar ones from mollusks and echinoderms
      suggests plausible pH-dependent quaternary transitions that may occur in response
      to proton binding and ligand release. Thus, these results provide the first step
      towards elucidating the structural basis for the strong allosteric properties of
      Lumbricus erythrocruorin.

PMID- 15504407
TI  - Developing a structure-function model for the cryptophyte phycoerythrin 545 using
      ultrahigh resolution crystallography and ultrafast laser spectroscopy.
AB  - Cryptophyte algae differ from cyanobacteria and red algae in the architecture of
      their photosynthetic light harvesting systems, even though all three are
      evolutionarily related. Central to cryptophyte light harvesting is the soluble
      antenna protein phycoerythrin 545 (PE545). The ultrahigh resolution crystal
      structure of PE545, isolated from a unicellular cryptophyte Rhodomonas CS24, is
      reported at both 1.1A and 0.97A resolution, revealing details of the conformation
      and environments of the chromophores. Absorption, emission and polarized steady
      state spectroscopy (298K, 77K), as well as ultrafast (20fs time resolution)
      measurements of population dynamics are reported. Coupled with complementary
      quantum chemical calculations of electronic transitions of the bilins, these
      enable assignment of spectral absorption characteristics to each chromophore in
      the structure. Spectral differences between the tetrapyrrole pigments due to
      chemical differences between bilins, as well as their binding and interaction
      with the local protein environment are described. Based on these assignments, and
      considering customized optical properties such as strong coupling, a model for
      light harvesting by PE545 is developed which explains the fast, directional
      harvesting of excitation energy. The excitation energy is funnelled from four
      peripheral pigments (beta158,beta82) into a central chromophore dimer
      (beta50/beta61) in approximately 1ps. Those chromophores, in turn, transfer the
      excitation energy to the red absorbing molecules located at the periphery of the
      complex in approximately 4ps. A final resonance energy transfer step sensitizes
      just one of the alpha19 bilins on a time scale of 22ps. Furthermore, it is
      concluded that binding of PE545 to the thylakoid membrane is not essential for
      efficient energy transfer to the integral membrane chlorophyll a-containing
      complexes associated with PS-II.

PMID- 15504408
TI  - The complex between hydrogenase-maturation proteins HypC and HypD is an
      intermediate in the supply of cyanide to the active site iron of [NiFe]
      hydrogenases.
AB  - Carbamoylphosphate has been shown to be the educt for the synthesis of the CN
      ligands of the NiFe metal centre of hydrogenases from Escherichia coli. In the
      absence of carbamoylphosphate, cells accumulate a complex of two hydrogenase
      maturation proteins, namely HypC and HypD for the synthesis of hydrogenase 3. A
      procedure for the purification of wild-type HypD protein or of a biologically
      active derivative carrying the Strep-tagII((R)) at the N terminus has been
      developed. HypD is a monomeric protein possessing about 4 mol of iron per mol of
      protein. Electron paramagnetic resonance (EPR) and Mossbauer spectroscopy
      demonstrated that the iron is present as a diamagnetic [4Fe-4S](2+) cluster. The
      complex between HypC and HypD can be cross-linked by a number of thiol and
      primary amine-specific linkers. When HypD and HypC were overproduced side-by-side
      with HypE, the HypC-HypD complex contained substoichiometric amounts of HypE
      whose proportion in the complex could be augmented when HypF was also
      overproduced. HypE trapped in this complex could be carbamoylated by protein HypF
      and after dehydration transferred the cyano group to the HypC-HypD part of the
      complex. Free HypC and HypD were not cyanated by HypE-CN. An active HypC-HypD
      complex from anaerobic cells was inactivated by incubation with K(3)[Fe(CN)(6)]
      but not with K(4)[Fe(CN)(6)]. The results suggest the existence of a dynamic
      complex between the hydrogenase maturation proteins HypD, HypC, HypE and HypF,
      which is the site of ligand biosynthesis and attachment to the iron atom of the
      NiFe site in hydrogenase 3.

PMID- 15504409
TI  - The tolerance of a modular protein to duplication and deletion of internal
      repeats.
AB  - Ankyrin repeat polypeptides contain repeated structural elements that pack to
      produce modular architectures lacking in close contacts between distant segments
      of the polypeptide chain. Despite this lack of sequence-distant contacts, ankyrin
      repeat polypeptides have been shown to fold in a cooperative manner. To determine
      the distance over which cooperative interactions can be propagated in a repeat
      protein, and to investigate the tolerance to internal duplication and deletion of
      modules, we have constructed a series of ankyrin repeat variants of the Notch
      ankyrin domain in which repeat number is varied by duplication and deletion of
      internal repeats. A construct with two copies of the fifth ankyrin repeat shows a
      modest increase in stability compared to the parent construct and retains
      apparent two-state unfolding behavior. Although constructs containing three and
      four copies of the fifth repeat retain this increased resistance to urea, they
      exhibit broad, multi-state unfolding transitions compared to the parent
      construct. For the Notch ankyrin domain, these larger constructs may represent a
      limit beyond which full cooperativity cannot be maintained. Deletions of internal
      repeats from the Notch ankyrin domain significantly destabilize the domain. This
      severe destabilization, which is larger than that resulting from end-repeat
      deletion, may arise from unfavorable interactions within the new non-native
      interfaces produced by internal repeat deletion. These results demonstrate both
      an asymmetry between the duplication and deletion of internal repeats, and a
      difference between deletion of internal and end-repeats, suggesting preferred
      mechanisms for evolution of repeat proteins.

PMID- 15504410
TI  - Kinetic stability and crystal structure of the viral capsid protein SHP.
AB  - SHP, the capsid-stabilizing protein of lambdoid phage 21, is highly resistant
      against denaturant-induced unfolding. We demonstrate that this high functional
      stability of SHP is due to a high kinetic stability with a half-life for
      unfolding of 25 days at zero denaturant, while the thermodynamic stability is not
      unusually high. Unfolding experiments demonstrated that the trimeric state (also
      observed in crystals and present on the phage capsid) of SHP is kinetically
      stable in solution, while the monomer intermediate unfolds very rapidly. We also
      determined the crystal structure of trimeric SHP at 1.5A resolution, which was
      compared to that of its functional homolog gpD. This explains how a tight network
      of H-bonds rigidifies crucial interpenetrating residues, leading to the observed
      extremely slow trimer dissociation or denaturation. Taken as a whole, our results
      provide molecular-level insights into natural strategies to achieve kinetic
      stability by taking advantage of protein oligomerization. Kinetic stability may
      be especially needed in phage capsids to allow survival in harsh environments.

PMID- 15504411
TI  - The folding of spectrin domains I: wild-type domains have the same stability but
      very different kinetic properties.
AB  - The study of proteins with the same architecture, but different sequence has
      proven to be a valuable tool in the protein folding field. As a prelude to
      studies on the folding mechanism of spectrin domains we present the kinetic
      characterisation of the wild-type forms of the 15th, 16th, and 17th domains of
      chicken brain alpha-spectrin (referred to as R15, R16 and R17, respectively). We
      show that the proteins all behave in a two-state manner, with different kinetic
      properties. The folding rate varies remarkably between different members, with a
      5000-fold variation in folding rate and 3000-fold variation in unfolding rate
      seen for proteins differing only 1 kcal mol(-1) in stability. We show clear
      evidence for significant complexity in the energy landscape of R16, which shows a
      change in amplitude outside the stopped-flow timescale and curvature in the
      unfolding arm of the chevron plot. The accompanying paper describes the
      characterisation of the folding pathway of this domain.

PMID- 15504412
TI  - The folding of spectrin domains II: phi-value analysis of R16.
AB  - Studies on the folding of helical proteins have shown a wide range of different
      mechanisms and highlighted the importance of helical propensity as a factor in
      determining folding mechanism. Here, we contribute to this interesting field with
      the protein engineering phi-value analysis of the 16th domain of chicken brain
      alpha-spectrin, R16. The fortuitous curvature seen in the unfolding arm of the
      chevron plot allows us to investigate both early and late events in folding. R16
      is the first two-state helical protein for which this has been possible.

PMID- 15504413
TI  - Do proteins always benefit from a stability increase? Relevant and residual
      stabilisation in a three-state protein by charge optimisation.
AB  - The vast majority of our knowledge on protein stability arises from the study of
      simple two-state models. However, proteins displaying equilibrium intermediates
      under certain conditions abound and it is unclear whether the energetics of
      native/intermediate equilibria is well represented in current knowledge. We
      consider here that the overall conformational stability of three-state proteins
      is made of a "relevant" term and a "residual" one, corresponding to the free
      energy differences of the native to intermediate (N-to-I) and intermediate to
      denatured (I-to-D) equilibria, respectively. The N-to-I free energy difference is
      considered to be the relevant stability because protein-unfolding intermediates
      are likely devoid of biological activity. We use surface charge optimisation to
      first increase the overall (N-to-D) stability of a model three-state protein
      (apoflavodoxin) and then investigate whether the stabilisation obtained is
      realised into relevant or into residual stability. Most of the mutations designed
      from electrostatic calculations or from simple sequence conservation analysis
      produce large increases in the overall stability of the protein. However, in most
      cases, this simply leads to similarly large increases of the residual stability.
      Two mutations, nevertheless, show a different trend and increase the relevant
      stability of the protein substantially. When all the mutations are mapped onto
      the structure of the apoflavodoxin thermal-unfolding intermediate (obtained
      independently by equilibrium phi-analysis and NMR) they cluster perfectly so that
      the mutations increasing the relevant stability appear in the small unstructured
      region of the intermediate and the others in the native-like region. This
      illustrates the need for specific investigation of N-to-I equilibria and the
      structure of protein intermediates, and indicates that it is possible to
      rationally stabilise a protein against partial unfolding once the structure of
      the intermediate conformation is known, even if at low resolution.

PMID- 15504414
TI  - Structure of stable protein folding intermediates by equilibrium phi-analysis:
      the apoflavodoxin thermal intermediate.
AB  - Protein intermediates in equilibrium with native states may play important roles
      in protein dynamics but, in cases, can initiate harmful aggregation events.
      Investigating equilibrium protein intermediates is thus important for
      understanding protein behaviour (useful or pernicious) but it is hampered by
      difficulties in gathering structural information. We show here that the phi
      analysis techniques developed to investigate transition states of protein folding
      can be extended to determine low-resolution three-dimensional structures of
      protein equilibrium intermediates. The analysis proposed is based solely on
      equilibrium data and is illustrated by determination of the structure of the
      apoflavodoxin thermal unfolding intermediate. In this conformation, a large part
      of the protein remains close to natively folded, but a 40 residue region is
      clearly unfolded. This structure is fully consistent with the NMR data gathered
      on an apoflavodoxin mutant designed specifically to stabilise the intermediate.
      The structure shows that the folded region of the intermediate is much larger
      than the proton slow-exchange core at 25 degrees C. It also reveals that the
      unfolded region is made of elements whose packing surface is more polar than
      average. In addition, it constitutes a useful guide to rationally stabilise the
      native state relative to the intermediate state, a far from trivial task.

PMID- 15504415
TI  - Identification of residues in the human guanylate-binding protein 1 critical for
      nucleotide binding and cooperative GTP hydrolysis.
AB  - The guanylate-binding proteins (GBPs) form a group of interferon-gamma inducible
      GTP-binding proteins which belong to the family of dynamin-related proteins. Like
      other members of this family, human guanylate-binding protein 1 (hGBP1) shows
      nucleotide-dependent oligomerisation that stimulates the GTPase activity of the
      protein. A unique feature of the GBPs is their ability to hydrolyse GTP to GDP
      and GMP. In order to elucidate the relationship between these findings, we
      designed point mutants in the phosphate-binding loop (P-loop) as well as in the
      switch I and switch II regions of the protein based on the crystal structure of
      hGBP1. These mutant proteins were analysed for their interaction with guanine
      nucleotides labeled with a fluorescence dye and for their ability to hydrolyse
      GTP in a cooperative manner. We identified mutations of amino acid residues that
      decrease GTPase activity by orders of magnitude a part of which are conserved in
      GTP-binding proteins. In addition, mutants in the P-loop were characterized that
      strongly impair binding of nucleotide. In consequence, together with altered
      GTPase activity and given cellular nucleotide concentrations this results in
      hGBP1 mutants prevailingly resting in the nucleotide-free (K51A and S52N) or the
      GTP bound form (R48A), respectively. Using size-exclusion chromatography and
      analytical ultracentrifugation we addressed the impact on protein
      oligomerisation. In summary, mutants of hGBP1 were identified and biochemically
      characterized providing hGBP1 locked in defined states in order to investigate
      their functional role in future cell biology studies.

PMID- 15504416
TI  - Replacement of staphylococcal nuclease hydrophobic core residues with those from
      thermophilic homologues indicates packing is improved in some thermostable
      proteins.
AB  - The importance of tight hydrophobic core packing in stabilizing proteins found in
      thermophilic organisms has been vigorously disputed. Here, portions of the cores
      found in three thermophilic homologues were transplanted into the core of
      staphylococcal nuclease, a protein of modest stability. Packing of the core was
      evaluated by comparing interaction energy of the three mutants to the
      comprehensive mutant library built up previously at these same sites in
      staphylococcal nuclease. It was found that the interaction energy of one
      thermophilic sequence is extraordinarily favorable and the interaction energies
      of other two transplanted thermophilic sequences are good, comparable to the
      interaction energies of mutant cores based on cores found in mesophilic
      homologues. As expected when transferring just a portion of the core sequence,
      the mutant proteins were destabilized overall relative to wild-type
      staphylococcal nuclease. The overall conclusion is that improvement of packing
      interactions is a mechanism to confer stability employed in some proteins from
      thermophiles, but not all.

PMID- 15504417
TI  - Oncogenic mutations reduce the stability of SRC kinase.
AB  - The oncogenic potential of the viral tyrosine kinase v-Src is due to its
      constitutive activity. Unlike the highly homologous cellular c-Src kinase, a C
      terminal deletion of the regulatory tail and numerous point mutations make the
      viral kinase uncontrollable. To determine the basis of these differences, we
      analysed the structure and stability of v-Src and c-Src in vitro. We show that
      the stability of v-Src against unfolding and irreversible aggregation is
      significantly lower than that of c-Src. Furthermore, in v-Src hydrophobic
      residues are more exposed already in the native state. In consequence, v-Src was
      found to be inactive close to physiological temperatures. We thus suggest that
      the ensemble of mutations that transform c-Src into the oncogenic variant cause a
      concomitant destabilisation of the kinase.

PMID- 15504418
TI  - Co-occurrence of 12-month mood and anxiety disorders and personality disorders in
      the US: results from the national epidemiologic survey on alcohol and related
      conditions.
AB  - The objective of this study was to determine the prevalence and co-occurrence of
      DSM-IV personality disorders (PDs) among individuals with current DSM-IV mood and
      anxiety disorders in the US population and among individuals who sought treatment
      for such mood or anxiety disorders. Face-to-face interviews were conducted with
      43,093 individuals, 18 years and older, in the National Institute on alcohol
      abuse and alcoholism's 2001-2002 National epidemiologic survey on alcohol and
      related conditions (NESARC). Odds ratios (ORs) were calculated to determine the
      prevalence and associations between current DSM-IV axis I and axis II disorders.
      Associations between mood, anxiety and PDs were all positive and statistically
      significant. Avoidant and dependent PDs were more strongly related to mood and
      anxiety disorders than other PDs. Associations between obsessive-compulsive PD
      and mood and anxiety disorders were significant, but much weaker. Paranoid and
      schizoid PDs were most strongly related to dysthymia, mania, panic disorder with
      agoraphobia, social phobia and generalized anxiety disorder, while histrionic and
      antisocial PDs were most strongly related to mania and panic disorder with
      agoraphobia. Results of this study highlight the need for further research on
      overlapping symptomatology, factors giving rise to the associations and the
      treatment implications of these disorders when comorbid.

PMID- 15504419
TI  - Dimensions of intelligence in schizophrenia: evidence from patients with
      preserved, deteriorated and compromised intellect.
AB  - There is a growing literature describing a subgroup of "high-functioning" people
      with schizophrenia who show preserved intellectual ability (IQ). A detailed
      characterisation of the cognitive abilities of this group may be important in
      targeting appropriate treatment, management and services for patients with
      schizophrenia. It is a widely held belief that variation in cognitive processing
      speed is the basis of individual differences in intelligence. The main objective
      of this study was to identify subgroups of schizophrenia patients with preserved
      (N=45), deteriorated (N=47) and compromised (N=17) intellect in order to study
      whether these subgroups differ in specific cognitive abilities (e.g. executive
      functions) or in general cognitive processing speed, as measured with an
      inspection time (IT) task. The patients who displayed an average estimated
      premorbid IQ, with no evidence of IQ decline (premorbid-current IQ difference <10
      points), were found to show better performance on measures of executive function
      (continuous performance task, verbal fluency) compared with patients in the
      deteriorated and compromised subgroups. Nevertheless, this represented
      significantly impaired performance relative to healthy controls. In contrast, the
      average inspection times of patients with preserved IQ were as slow as those
      obtained in the deteriorated or compromised groups, indicating that high
      functioning patients are impaired in terms of cognitive processing speed.
      Furthermore, the average IT for all schizophrenia groups was significantly slower
      than that of healthy controls. These findings suggest that high functioning
      patients with schizophrenia exhibit enduring cognitive difficulties that may
      impact on their ability to benefit from rehabilitation interventions.

PMID- 15504420
TI  - The Munich vulnerability study on affective disorders: premorbid neuroendocrine
      profile of affected high-risk probands.
AB  - One of the most characteristic alterations in depression is a disturbed
      regulation of the hypothalamic-pituitary-adrenocortical (HPA) system. A function
      test combining the pre-treatment of 1.5 mg dexamethasone (DEX) with a challenge
      of 100 microg corticotropin-releasing hormone (CRH) reveals a pathological
      increase in the adrenocorticotropin and cortisol release in patients with major
      depression. These changes partially persist after successful treatment with
      remission and therefore, might represent trait or vulnerability markers. To
      further address this question, we were investigating the premorbid neuroendocrine
      profile of 74 healthy high-risk probands (HRPs) with a positive family history
      for affective disorders. The aim was to identify premorbid vulnerability factors.
      During the observation period, 19 HRPs developed an affective disorder. Their
      premorbid DEX/CRH test results were compared with 19 age- and sex matched
      controls. No significant differences could be observed between these two groups.
      Our results suggest that a dysregulated HPA system indicated by this function
      test can rather be regarded as a neurobiological scar developing during the
      course of affective disorders.

PMID- 15504421
TI  - Proton magnetic resonance spectroscopy (1H-MRS) of hippocampus, basal ganglia,
      and vermis of cerebellum in schizophrenia associated with idiopathic unconjugated
      hyperbilirubinemia (Gilbert's syndrome).
AB  - OBJECTIVE: Whether patients with schizophrenia-associated idiopathic unconjugated
      hyperbilirubinemia (Gilbert's syndrome, GS) have specific changes in brain
      metabolism was examined in this study. METHOD: This study applied proton magnetic
      resonance spectroscopy (1H-MRS) to the hippocampus, basal ganglia, and vermis of
      the cerebellum of schizophrenic patients with GS (n=15) or without GS (n=15), all
      diagnosed according to DSM-IV criteria, and healthy subjects (n=15). RESULTS: In
      the hippocampus, schizophrenic patients with GS showed a significant decrease of
      N-acetyl aspartate/creatine-phosphocreatinine (NAA/Cr) and myoinositol/creatine
      phosphocreatinine (mI/Cr) ratios compared to healthy subjects and schizophrenic
      patients without GS, while schizophrenic patients without GS showed only a
      significant decrease of NAA/Cr compared to healthy subjects. In the basal
      ganglia, schizophrenic patients with GS showed a significant decrease of ml/Cr
      compared to schizophrenic patients without GS and healthy subjects, and
      schizophrenic patients with GS showed a significant decrease of NAA/Cr compared
      to healthy subjects. In the vermis of the cerebellum, schizophrenic patients with
      GS showed only a significant decrease of ml/Cr compared to healthy subjects,
      although schizophrenic patients without GS did not show a significant decrease of
      ml/Cr compared to healthy subjects. CONCLUSION: The findings suggest that
      schizophrenia with GS is a more severe sub-type with regard to brain metabolism.

PMID- 15504422
TI  - Elevation of liver enzyme levels during psychopharmacological treatment is
      associated with weight gain.
AB  - Increased circulating levels of liver enzymes emerging during treatment with
      psychotropic drugs are frequently encountered and, in general, attributed to drug
      metabolism or toxic effects. Because obesity was shown to be associated with
      elevated liver enzyme levels in different non-psychiatric study samples, we
      hypothesized that drug-induced weight gain might be an additional causative
      factor. We tested this hypothesis in 67 inpatients who received
      psychopharmacological treatment across five weeks. Stepwise linear regression was
      used to predict changes in the serum levels of aspartate-amino transferase (ASAT)
      and alanine-amino transferase (ALAT) by changes in the body mass index (BMI), by
      changes in other biological parameters related to body weight (tumor necrosis
      factor-alpha [TNF-alpha], soluble TNF receptors [sTNF-R], interleukin-6 [IL-6],
      leptin plasma levels) and by the respective liver enzyme baseline level. BMI
      changes from baseline to endpoint were significantly associated with the changes
      in ALAT and ASAT levels across five weeks of treatment and with ALAT and ASAT
      levels at the end point of the study. The baseline levels of ALAT and ASAT also
      had a significant impact on these liver enzyme level changes, whereas all other
      variables had not. These results suggest that weight gain-associated metabolic
      changes occurring during treatment with psychotropic drugs have consistent and
      clinically relevant effects on the liver.

PMID- 15504423
TI  - Duloxetine 60 mg once-daily in the treatment of painful physical symptoms in
      patients with major depressive disorder.
AB  - BACKGROUND: While emotional symptoms such as depressed mood and loss of interest
      have traditionally been considered to constitute the core symptoms of major
      depressive disorder (MDD), the prevalence and importance of painful physical
      symptoms such as back pain, abdominal pain, and musculoskeletal pain is becoming
      increasingly appreciated. Antidepressants possessing dual
      serotonin/norepinephrine (5-HT/NE) reuptake inhibition may demonstrate greater
      efficacy in the alleviation of pain. The efficacy of duloxetine, a balanced and
      potent dual reuptake inhibitor of 5-HT and NE, was evaluated within a cohort of
      depressed patients with associated painful physical symptoms. METHODS: In this
      multicenter, double-blind, placebo-controlled study, patients meeting DSM-IV
      criteria for MDD were randomized to receive placebo (N=141) or duloxetine 60 mg
      QD (N=141). Patients were required to have a 17-item Hamilton Rating Scale for
      Depression (HAMD17) total score 15, a Clinical Global Impression of Severity (CGI
      S) score 4, and a Brief Pain Inventory (BPI) Average Pain score 2 at baseline.
      The primary efficacy measure was the BPI Average Pain score, while secondary
      measures included other BPI items, the HAMD17 total score, CGI-S, the Patient
      Global Impression of Improvement (PGI-I) scale, Visual Analog Scales (VAS) for
      pain, and the Symptom Questionnaire, Somatic Subscale (SQSS). Safety was
      evaluated by recording treatment-emergent adverse events (spontaneously
      reported), vital signs, and laboratory analytes. RESULTS: Mean changes in BPI
      Average Pain for duloxetine- and placebo-treated patients differed significantly
      at most visits, but only approached significance at endpoint p=0.066. For the
      main effect of treatment (pooling all visits), significant advantages for
      duloxetine-treated patients were found in 10 of 11 assessed BPI pain severity and
      pain interference items, in addition to VAS overall pain and back pain. Mean
      changes in pain measures for duloxetine-treated patients corresponded to
      improvements of 25-50%, compared with 19-39% for placebo. Mean changes at
      endpoint in depression rating scales (HAMD17, CGI-S, PGI-I) did not differ
      significantly between duloxetine and placebo treatment groups due to unusually
      high placebo response. The magnitude of placebo treatment effects (as measured by
      HAMD17 total score and Maier subscale) was significantly smaller in patients with
      1 previous depressive episode, compared to those patients with no previous
      episodes. In patients with 1 previous depressive episode the advantage of
      duloxetine over placebo was similar to previous studies. Rates of discontinuation
      due to adverse events were 14.2% vs. 2.1% for duloxetine and placebo,
      respectively p<0.001. Treatment-emergent adverse events reported at a
      significantly higher rate by duloxetine-treated patients included nausea, dry
      mouth, fatigue, and decreased appetite. CONCLUSIONS: In this study, duloxetine
      (60 mg QD) was shown to be an effective treatment for the painful physical
      symptoms which are frequently associated with depression. Improvements in pain
      severity occurred independently of changes in depressive symptom severity.

PMID- 15504424
TI  - Women's sleep in health and disease.
AB  - A huge amount of knowledge about sleep has accumulated during the last 5 decades
      following the discovery of rapid eye movement (REM) sleep. Nevertheless, there
      are numerous areas of considerable ignorance. One of these concerns the
      particularities of sleep in women. Most basic and clinical studies have been
      performed in male subjects, and only very recently research groups around the
      world have addressed women's sleep in health and disease. In this review, we
      summarize the present knowledge on the influence of oestrogens on the brain and
      on the distinctive changes of sleep across the menstrual cycle, during pregnancy
      and menopause. In addition, studies in female rodents are reviewed as well as the
      knowledge on female peculiarities regarding the interactions between sleep
      regulation and age-related changes in circadian rhythms. We also address specific
      aspects of sleep loss and sleep disorders in women. Finally, very recent studies
      on the sociology of sleep are summarized and future directions in the field are
      discussed.

PMID- 15504425
TI  - Sex-specific self-reported mood changes by patients with bipolar disorder.
AB  - INTRODUCTION: While the prevalence of bipolar disorder I is similar between men
      and women, the clinical course may differ. This study investigated if there are
      differences in the clinical presentation of bipolar disorder between the sexes.
      METHODS: Mood patterns were documented using ChronoRecord software for self
      reporting. Patients entered mood, medications, sleep, life events and menstrual
      data daily acquired over the period of three months. 8662 Days of data were
      received from 80 patients: 3483 days from 35 men and 5179 days from 45 women.
      RESULTS: The distribution of the time spent in mood categories differed between
      men and women (P<0.001). Men were depressed 17.0% of the time, euthymic 74.0% of
      the time and manic 5.6% of the time. Women were depressed 28.3% of the time,
      euthymic 64.2% of the time and manic 7.5% of the time. Over 80% of all reported
      symptoms for both sexes were mild. Women exhibited large mood fluctuations
      (greater than 10 in either direction on a 100-unit scale) more frequently than
      men. Most of the reproductive aged women (55%) reported significant mood changes
      across the menstrual cycle. CONCLUSIONS: The clinical course of bipolar disorder
      differed between the sexes. Women reported depression and large fluctuations in
      mood more frequently than men. Women also experienced mood changes across the
      menstrual cycle.

PMID- 15504426
TI  - Affective dysregulation and dissociative experience in female patients with
      borderline personality disorder: a startle response study.
AB  - Affective dysregulation and dissociation are currently discussed as core features
      of borderline personality disorder (BPD). Affective dysregulation is hypothesized
      to be correlated with increased amygdala functioning and dissociation is linked
      to inhibited processing on the amygdala and dampened autonomic output, according
      to the corticolimbic disconnection model of dissociation from Sierra and Berrios
      [Biological Psychiatry 44 (1998) 898]. We assessed startle response, which is
      mainly mediated by the amygdala, to investigate the relationship between
      affective dysregulation and dissociation. We hypothesized that patients with BPD
      would reveal enhanced responses to startling tones, but that these would be
      lessened by the presence of state dissociative experiences. 21 unmedicated female
      patients with BPD and 21 healthy female controls listened to 15 startling tones
      (95-dB, 500-ms, 1000-Hz) while heart rate, skin conductance and orbicularis oculi
      electromyogram responses were measured. Covariance analysis showed that the BPD
      group had a significantly higher startle response in the electromyogram as
      compared to controls. Furthermore, present-state dissociative experiences
      significantly influenced the startle response. Patients with low dissociative
      experiences revealed enhanced startle responses whereas patients with high
      dissociative experiences showed reduced responses. Our data support affective
      dysregulation in BPD as well as the corticolimbic disconnection model of
      dissociation, at least for EMG. Furthermore, it highlights the importance of
      assessing present-state dissociation in basic research as well as psychotherapy.

PMID- 15504427
TI  - Sleep investigations in erectile dysfunction.
AB  - Regarding the aetiology of erectile dysfunction, beside numerous organic causes
      in many cases psychological factors play an important role. The
      pathophysiological mechanisms underlying the so-called psychogenic erectile
      dysfunction are not yet understood. Based on a neurobiological approach to
      psychogenic erectile dysfunction, polysomnographic investigations were carried
      out with the aim of identifying possible alterations of the sleep EEG. 24 male
      patients with psychogenic erectile dysfunction without detectable organic factors
      or other mental disorders were studied in the sleep laboratory, as well as an age
      matched control group without sexual dysfunctions. Beside a reduction of sleep
      efficacy, the most prominent finding was a shortening of REM latency in the
      patients compared to the controls. Moreover, spectral analysis revealed a reduced
      theta power for all sleep stages and a reduced delta power for stage II and slow
      wave sleep in the patients. The findings support the point of view that
      psychogenic erectile dysfunction is an organic disorder of the brain. The sleep
      EEG abnormalities may reflect dysregulations in limbic structures which are
      suggested to be involved in the pathophysiology of sexual dysfunctions. As these
      alterations had also been reported for other mental disorders, particularly
      depression, they appear to be non-specific biological abnormalities for different
      psychiatric syndromes, including psychogenic erectile dysfunction.

PMID- 15504428
TI  - Effects of haloperidol and risperidone on psychomotor performance relevant to
      driving ability in schizophrenic patients compared to healthy controls.
AB  - The effects of antipsychotic treatment on the psychomotor performance and driving
      ability of schizophrenic patients is subject of investigation. The present study
      was designed to evaluate the effects of an atypical neuroleptic (risperidone) in
      comparison to a conventional dopamine antagonist neuroleptic (haloperidol) on
      several dimensions of psychomotor performance (visual perception, attention,
      reaction time, and sensorimotor performance) considered to be of relevance in
      evaluating driving fitness. Psychomotor performance was assessed by means of the
      ART 90 (act-and-react test), a computerized test battery which is frequently used
      in diagnosis of psychomotor performance. The 40 participating patients were
      examined at discharge following psychopathological stabilisation; 20 received
      haloperidol medication, 20 received the atypical neuroleptic risperidone.
      Nineteen healthy individuals were studied as a control group. Our findings
      indicate a remarkably reduced psychomotor performance in both groups of
      schizophrenic patients compared to healthy controls. We did find a significant
      but low correlation between age and some items of the RST3 and between age and
      the tracking performance on the PVT. The younger patients showed a better test
      performance than older patients. The BPRS-score was significantly correlated with
      only two items of the RST3. However, patients under treatment with risperidone
      showed significantly better results compared to patients treated with
      haloperidol. Only one (5%) subject passed all subtests without major failures and
      could be regarded as competent to drive. Among patients with risperidone, seven
      patients (35%) passed all test parameters without major failures. Clinical
      implications of these findings are discussed.

PMID- 15504430
TI  - Protein phosphorylation in Nicotiana tabacum cells in response to perception of
      lipopolysaccharides from Burkholderia cepacia.
AB  - Bacterial LPS have the ability to act as modulators of the innate immune response
      in plants. Complex and largely unresolved perception systems exist for LPS on the
      plant cell surfaces that lead to the activation of multiple intracellular defense
      signaling pathways. The aim of the present study was to investigate the
      perception mechanism of cultured Nicotiana tabacum cells towards LPS from
      Burkholderia cepacia (LPS(B.cep.)), with regard to the role of protein
      phosphorylation during signal perception-related responses to gain a better
      understanding of the chemosensory perception of LPS elicitor signals in plant
      cells. In vivo labeling of protein phosphorylation events during signal
      transduction indicated the rapid phosphorylation of several proteins with the
      hyperphosphorylation of two proteins of 28 and 2 kDa, respectively. Significant
      differences and de novo LPS-induced phosphorylation were also observed with two
      dimensional analysis. The protein kinase inhibitor, staurosporine, totally
      inhibited the extracellular alkalinization response induced by LPS(B.cep.), while
      the oxidative burst was only partially inhibited by staurosporine. Inhibition of
      protein phosphatase activity by calyculin A intensified the LPS(B.cep.)
      responses. The results indicate that perception- and signal transduction
      responses during LPS(B.cep.) elicitation of tobacco cells require a balance
      between the actions of certain protein kinases and protein phosphatases.

PMID- 15504429
TI  - Aggression and psychopathology in treatment-resistant inpatients with
      schizophrenia and schizoaffective disorder.
AB  - Positive psychotic symptoms, such as threat/"control-override" delusions or
      command hallucinations, have been related to aggression in patients with
      schizophrenia. However, retrospective data collection has hampered evaluation of
      the direct influence of psychopathology on aggressive behavior. In this study, we
      monitored aggressive behavior and psychopathology prospectively and in close
      temporal proximity in 157 treatment-resistant inpatients diagnosed with chronic
      schizophrenia or schizoaffective disorder participating in a 14-week double-blind
      clinical trial. Aggressive behavior was rated with the overt aggression scale
      (OAS). Psychopathology was assessed using the positive and negative syndrome
      scale (PANSS). At baseline, subjects who would be aggressive during the study had
      higher scores on only two PANSS items: hostility and poor impulse control. During
      the study PANSS positive subscale scores were significantly higher in aggressive
      subjects. Total PANSS scores were higher within 3 days of an aggressive incident,
      as were positive and general psychopathology subscale scores. However, in a
      smaller subsample for whom PANSS ratings were available within 3 days before
      aggressive incidents, only scores on the PANSS positive subscale were
      significantly higher. These findings in chronic, treatment resistant inpatients
      support the view that positive symptoms may lead to aggression.

PMID- 15504431
TI  - Steroid profiles of transgenic tobacco expressing an Actinomyces 3-hydroxysteroid
      oxidase gene.
AB  - Previously, we have shown that the expression of a 3-hydroxysteroid-oxidase gene
      in transgenic tobacco initiated a series of biochemical events leading to the
      conversion of sterol to stanol. As a result, the plants maintained a diminished
      sterol pool and a modified relative sterol ratio but demonstrated no observable
      morphological abnormalities. The maintenance of normal higher plant physiology in
      the absence of particular sterols or in the presence of modified sterol ratios is
      controversial. In this report, we present additional biochemical and
      physiological characteristics of transgenic tobacco expressing an Actinomyces 3
      hydroxysteroid-oxidase gene. The total steroid accumulated in the transgenic
      plants is 6-fold higher than in control plants and consists of sterol, 3
      ketosteroid and stanol. The relative abundance of sterols within whole plant and
      individual organs is grossly altered as ethylated side chain sterols account for
      99% of the total sterol pool in the transgenic tobacco. Stigmasterol is readily
      apparent in all tissues and cholesterol is found at measurable levels in specific
      organs, while campesterol and sitosterol are detected at trace levels in the
      transgenic plants. Stanols and 3-ketosteroids accumulate in all tissues and
      represent 77% of the measurable steroid pool in the transgenic plants. The sum of
      sterol, the respective 3-ketosteroid plus stanol provide a relative abundance of
      steroid, which is similar to the abundance of sterol accumulated in control
      tissue. In vitro photosynthetic electron transport measurements demonstrate
      altered activity of chloroplasts under a variety of reaction conditions,
      indicating a link between the modified steroid pool and a modulation of
      chloroplast membrane function.

PMID- 15504432
TI  - Tocopherol and tocotrienol accumulation during development of caryopses from
      barley (Hordeum vulgare L.).
AB  - Tocotrienols are lipophilic antioxidants belonging to the tocochromanols, better
      known as vitamin E. Although present in cereal grains in high quantities not much
      is known about their function in plants. In a detailed study the temporal and
      spatial accumulation of tocotrienols and tocopherols during grain development in
      two barley cultivars was analyzed. Tocochromanols and lipids accumulated in
      parallel until 80% of the final dry weight of the kernels was reached. Later on
      the tocochromanol content did not change while the lipid content decreased.
      Generally, only about 13% of the tocochromanols were found in the germ fraction,
      whereas the pericarp fraction contained about 50% and the endosperm fraction
      about 37% of the tocochromanols. Altogether, about 85% of the tocochromanols were
      tocotrienols in both cultivars. In case of the tocopherols about 80% were found
      in the germ fraction and the remaining 20% in the pericarp fraction. Tocotrienols
      were almost equally present in the pericarp and the endosperm fraction.
      Individual forms of tocopherols and tocotrienols accumulated with different
      kinetics during barley grain development. The differences in distribution and
      accumulation indicate different functions of the individual tocochromanols during
      grain development.

PMID- 15504433
TI  - Exobasidium vexans infection of Camellia sinensis increased 2,3-cis isomerisation
      and gallate esterification of proanthocyanidins.
AB  - Infection of leaves of tea (Camellia sinensis (Kuntze) L, cv TRI 2025) which was
      susceptible to blister blight (Exobasidium vexans Massee), resulted in a shift of
      the proanthocyanidin stereochemistry away from 2,3-trans (e.g. catechin and
      gallocatechin) and towards 2,3-cis (e.g. epicatechin and epigallocatechin).
      Infection also resulted in increased gallic acid esterification of the initiating
      subunits of proanthocyanidins. This was shown by both mass spectroscopy and
      phloroglucinolysis. Proanthocyanidins isolated from healthy tissue had a
      predominantly 2,3-trans stereochemistry which accounted for 53% and 61% of the
      total initiating and extension units of proanthocyanidin, respectively.
      Conversely in infected tissue, proanthocyanidin subunits with a 2,3-trans
      stereochemistry accounted for 26% and 40% of the total initiating and extension
      units, respectively. Infection had little impact on the hydroxylation state of
      the B-rings of proanthocyanidins. The products of acid hydrolysis under oxidative
      conditions had a slight excess of di-hydroxylated B-rings with cyanidin
      accounting for 58.3+/-0.05% and 60.4+/-0.2% of the total anthocyanidin recovered
      following hydrolysis of proanthocyanidin isolated from infected and healthy
      leaves, respectively. Similar results were obtained by phloroglucinolysis.

PMID- 15504434
TI  - Accumulation of HDMBOA-Glc is induced by biotic stresses prior to the release of
      MBOA in maize leaves.
AB  - The effects of biotic stresses on the contents of benzoxazinones (Bxs) were
      investigated in maize leaves. When the causal agent of southern corn leaf blight,
      Bipolaris maydis, was inoculated on the third leaf, the amount of 2-hydroxy-4,7
      dimethoxy-1,4-benzoxazin-3-one glucoside (HDMBOA-Glc) increased, reaching a
      maximum level 48 h after inoculation. The inoculation of weakly pathogenic
      Curvularia lunata and non-pathogenic Alternaria alternata also resulted in
      accumulation of HDMBOA-Glc, and filtrates of the cultures of B. maydis, C. lunata
      and A. alternata also showed the accumulation of elicitor-active compounds by the
      fungi. Furthermore the infection of B. maydis induced formation of dark brown
      lesions, where most abundant Bx-related compound was 6-methoxy-2-benzoxazolinone
      (MBOA). The later is formed by degradation of DIMBOA and HDMBOA, whereas HDMBOA
      Glc was most abundant in the surrounding green tissues. Among the Bx-related
      compounds, MBOA exhibited the strongest inhibition of the germination of the
      conidia and of the growth of germ tubes of B. maydis, C. lunata and A. alternata.
      In addition to fungal infection, the feeding by rice armyworm larvae resulted in
      HDMBOA-Glc accumulation. These findings are discussed in relation to the possible
      ecological relevance of the conversion of DIMBOA-Glc into HDMBOA-Glc.

PMID- 15504435
TI  - The distribution of serine proteinase inhibitors in seeds of the Asteridae.
AB  - The Asteridae is one of the most successful clades of flowering plants comprising
      some 80,000 species. Despite this diversity, analysis of seeds from 398 species
      (representing 8 orders, 32 families and 181 genera) showed just two major types
      of serine proteinase inhibitors (PI). PIs of the potato inhibitor I family were
      widely distributed. These had M(r) of 7000-7500 and were inhibitory to subtilisin
      and one or more other proteinases (but only rarely elastase). The second major
      group was TI related to the well-characterised Bowman-Birk inhibitors of legume
      seeds but these varied widely in their sequences and structure. In addition to
      these two groups of inhibitors, seeds of the Solanaceae also often contained PI
      of the potato inhibitor II family while some other asterids contained inhibitors
      whose relationships were not established.

PMID- 15504436
TI  - Identification and biological evaluation of grapefruit oil components as
      potential novel efflux pump modulators in methicillin-resistant Staphylococcus
      aureus bacterial strains.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) and MSSA strains were treated
      with: (a) grapefruit oil (GFO) components, isolated by chromatography and
      characterised by NMR and mass spectroscopy; (b) antimicrobial agents, or (c) a
      combination of both to evaluate (MIC determination) intrinsic antibacterial
      activity and to determine whether GFO components could modulate bacterial
      sensitivity to the anti-bacterial agents. Preliminary data suggested that the
      grapefruit component 4-[[(E)-5-(3,3-dimethyl-2-oxiranyl)-3-methyl-2-pentenyl]oxy]
      7H-furo[3,2-g]chromen-7-one (2) enhances the susceptibility of test MRSA strains
      to agents, e.g., ethidium bromide and norfloxacin, to which these micro-organisms
      are normally resistant.

PMID- 15504437
TI  - Anti-plasmodial flavonoids from the stem bark of Erythrina abyssinica.
AB  - The ethyl acetate extract of the stem bark of Erythrina abyssinica showed anti
      plasmodial activity against the chloroquine-sensitive (D6) and chloroquine
      resistant (W2) strains of Plasmodium falciparum with IC(50) values of 7.9+/-1.1
      and 5.3+/-0.7 microg/ml, respectively. From this extract, a new chalcone,
      2',3,4,4'-tetrahydroxy-5-prenylchalcone (trivial name 5-prenylbutein) and a new
      flavanone, 4',7-dihydroxy-3'-methoxy-5'-prenylflavanone (trivial name, 5
      deoxyabyssinin II) along with known flavonoids have been isolated as the anti
      plasmodial principles. The structures were determined on the basis of
      spectroscopic evidence.

PMID- 15504438
TI  - Antioxidant activity of phenylpropanoid esters isolated and identified from
      Platycodon grandiflorum A. DC.
AB  - Platycodon grandiflorum A. DC (Campanulaceae) is used as a traditional oriental
      medicine and also as a food in Korea. Here we investigated its antioxidant
      activity, and isolated and identified its active compounds. Petroleum ether
      extracts from the whole root of P. grandiflorum were fractionated by silica gel
      column chromatography using a solvent gradient (petroleum ether:diethyl ether,
      v/v; 9:1-5:5). The 8:2 fraction showed a higher radical scavenging activity than
      the other fractions, and active compounds were purified from this fraction by
      reversed-phased HPLC. Two active compounds were identified as coniferyl alcohol
      esters of palmitic and oleic acids by FAB-MS, UV, IR and NMR spectroscopy. The
      antioxidant activities of these two compounds, which were evaluated by 1,1
      diphenyl-2-picrylhydrazyl (DPPH), superoxide and nitric oxide radical scavenging
      capacity, were found to be as high as those of BHT or BHA.

PMID- 15504439
TI  - Flavonoid glycosides and isoquinolinone alkaloids from Corydalis bungeana.
AB  - Two flavonol O-glycosides identified as the 3-O-alpha-arabinopyranosyl(1'''-
      >6'')-beta-glucopyranoside 7-O-beta-glucopyranosides of kaempferol and quercetin
      were isolated from the whole plant of Corydalis bungeana Turcz. together with
      eight known flavonol O-glycosides. Two isoquinolinone alkaloids were also
      obtained from the same source, including the new derivative, 6,7-methylenedioxy-2
      (6-acetyl-2,3-methylenedioxybenzyl)-1(2H)-isoquinolinone. The structures were
      determined by spectroscopic methods (NMR and high-resolution MS).

PMID- 15504440
TI  - C(25) highly branched isoprenoid alkenes from the marine benthic diatom
      Pleurosigma strigosum.
AB  - The hydrocarbon composition of the marine diatom Pleurosigma strigosum isolated
      from coastal Mediterranean sediments is described. A suite of five C(25) highly
      branched isoprenoid (HBI) alkenes with 2-5 double bonds were detected together
      with n-C(21:4) and n-C(21:5) alkenes and squalene. The analysis by (1)H and (13)C
      NMR spectroscopy of two isolated HBI alkenes allowed the structural
      identification of a novel C(25) HBI triene (2,6,10,14-tetramethyl-7-(3-methylpent
      4-enyl)-pentadeca-5E,13-diene) and the first identification in diatom cells of
      2,6,10,14-tetramethyl-7-(3-methylpent-4-enyl)-pentadec-5E-ene, an HBI previously
      detected in marine sediments and particulate matter. The other minor C(25) HBIs
      detected were a tetraene and a pentaene that have been previously identified in
      other diatoms from the genera Haslea and Rhizosolenia, and one other C(25)
      tetraene that could not be structurally identified. The structures of the HBI
      alkenes of P. strigosum were compared with those of C(25) homologues previously
      identified in three other Pleurosigma sp. (Pleurosigma intermedium, Pleurosigma
      planktonicum and Pleurosigma sp.). Unlike most structures previously reported,
      none of the HBI alkenes produced by P. strigosum showed an unsaturation at C7
      C20, or E/Z isomerism of the trisubstituted double bond at C9-C10 (whenever
      present).

PMID- 15504441
TI  - Bioactive apocarotenoids annuionones F and G: structural revision of annuionones
      A, B and E.
AB  - The polar bioactive fractions of Helianthus annuus cv. Stella and SH-222 have
      yielded eight apocarotenoids, two of them isolated for the first time as natural
      products (annuionones F and G). The isolation of higher amounts of annuionones A
      and E allowed us to realize a more comprehensive spectroscopical study. We
      propose a revised structure for annuionone A, B and E based on careful re
      analyses of new spectroscopical data.

PMID- 15504443
TI  - Analyzing prescription drugs as causes of death on death certificates..

PMID- 15504444
TI  - Breastfeeding and the risk of childhood leukemia: a meta-analysis.
AB  - OBJECTIVE: The authors used a meta-analytic technique to (1) quantify the
      evidence of an association between duration of breastfeeding and risk of
      childhood acute lymphoblastic leukemia (ALL) or acute myeloblastic leukemia
      (AML), (2) assess the influence of socioeconomic status (SES) on any such
      associations, and (3) discuss the implications of these findings for the
      evaluation of whether breastfeeding reduces the risk of childhood leukemia.
      METHODS: A fixed effects model was employed to systematically combine the results
      of 14 case-control studies addressing the effect of short-term (< or = 6 months)
      and long-term (>6 months) breastfeeding on the risk of childhood ALL and/or AML.
      Subgroup analyses of studies that did and did not adjust for SES were also
      performed. RESULTS: A significant, negative association was observed between long
      term breastfeeding and both ALL risk (odds ratio [OR]=0.76; 95% confidence
      interval [CI] 0.68, 0.84) and AML risk (OR=0.85; 95% CI 0.73, 0.98). Short-term
      breastfeeding was similarly protective for ALL and AML. Results for studies that
      adjusted and did not adjust for SES were not significantly different from the
      results for the 14 studies combined. CONCLUSIONS: This meta-analysis showed that
      both short-term and long-term breastfeeding reduced the risk of childhood ALL and
      AML, suggesting that the protective effect of breastfeeding might not be limited
      to ALL as earlier hypothesized. Potential bias introduced by different
      participation rates for case and control samples that differed in SES can be
      minimized by implementing larger case-control studies with SES-matched,
      population-based controls.

PMID- 15504445
TI  - What's going on? The question of time trends in autism.
AB  - Increases in the reported prevalence of autism and autistic spectrum disorders in
      recent years have fueled concern over possible environmental causes. The author
      reviews the available survey literature and finds evidence of large increases in
      prevalence in both the United States and the United Kingdom that cannot be
      explained by changes in diagnostic criteria or improvements in case
      ascertainment. Incomplete ascertainment of autism cases in young child
      populations is the largest source of predictable bias in prevalence surveys;
      however, this bias has, if anything, worked against the detection of an upward
      trend in recent surveys. Comparison of autism rates by year of birth for specific
      geographies provides the strongest basis for trend assessment. Such comparisons
      show large recent increases in rates of autism and autistic spectrum disorders in
      both the U.S. and the U.K. Reported rates of autism in the United States
      increased from < 3 per 10,000 children in the 1970s to > 30 per 10,000 children
      in the 1990s, a 10-fold increase. In the United Kingdom, autism rates rose from <
      10 per 10,000 in the 1980s to roughly 30 per 10,000 in the 1990s. Reported rates
      for the full spectrum of autistic disorders rose from the 5 to 10 per 10,000
      range to the 50 to 80 per 10,000 range in the two countries. A precautionary
      approach suggests that the rising incidence of autism should be a matter of
      urgent public concern.

PMID- 15504446
TI  - Hospital recruitment for the Smallpox Pre-Event Vaccination Program: experiences
      from Florida, Nebraska, New Jersey, and Tennessee, December 2002-June 2003.
AB  - The Smallpox Pre-Event Vaccination Program (SPVP) for public health and hospital
      based health care workers began on January 24, 2003. This report summarizes
      efforts made by health officials in Florida, Nebraska, New Jersey, and Tennessee
      to facilitate the voluntary participation of acute care hospitals in the SPVP.
      Seven common characteristics contributed to the success of programs in these four
      states: (1) early planning, building on existing competencies, and state
      government support, (2) carrying the program forward on a planned timeline with
      experienced vaccination staff, (3) use of multifaceted training activities, (4)
      use of mock scenarios and field exercises to avoid early problems, (5)
      establishment and fostering of good relationships and lines of communication with
      stakeholders and the mass media, (6) addressing liability and workers'
      compensation concerns prior to initiation of the SPVP, and (7) attention to
      vaccination clinic logistics.

PMID- 15504447
TI  - Physical partner violence and medicaid utilization and expenditures.
AB  - OBJECTIVES: Little research has addressed differences in health care expenditures
      among women who are currently experiencing intimate partner violence (IPV)
      compared with those who are not. The purpose of this work is to provide estimates
      of direct medical expenditure for physician, drug, and hospital utilization among
      Medicaid-eligible women who screened as currently experiencing IPV compared with
      those who are not currently experiencing IPV. METHODS: In this family practice
      based cross-sectional study, women were screened for current IPV using a 15-item
      Index of Spouse Abuse-Physical (ISA-P) between 1997 and 1998. Consents were
      obtained from study subjects to review Medicaid expenditure and utilization data
      for the same time period. RESULTS: Mean physician, hospital, and total
      expenditures were higher for those women with higher IPV scores compared with
      those who scored as not currently experiencing IPV, after adjusting for
      confounders. Higher IPV scores were associated with a three-fold increased risk
      of having a total expenditure over $5,000 (95% confidence interval [CI] 1.3,
      8.4). The mean total expenditure difference between the high IPV and no IPV
      groups was $1,064 (95% CI $623, $1506). The adjusted risk ratio for high IPV
      score and the log of total Medicaid expenditures was 2.3 (95% CI 1.2, 4.4).
      CONCLUSIONS: Women screened as experiencing higher IPV scores had higher Medicaid
      expenditures compared with women not currently experiencing IPV. Early IPV
      assessment partnered with effective clinic or community-based interventions may
      help to identify IPV earlier and reduce the health impact and cost of IPV.

PMID- 15504448
TI  - Household food security among migrant and seasonal latino farmworkers in North
      Carolina.
AB  - OBJECTIVE: Food insecurity is defined as lack of access at all times, due to
      economic barriers, to enough food for an active and healthy lifestyle. The
      objective of this study was threefold: to characterize levels of food security,
      food insecurity, and hunger among migrant and seasonal Latino farmworkers; to
      assess predictors of food insecurity for this group; and to describe the
      strategies farmworkers use to cope with food insecurity. METHODS: Adults from 102
      farmworker households in North Carolina responded to a survey that used a Spanish
      language adaptation of the U.S. Household Food Security Survey Module and
      questions about sociodemographic characteristics and food behaviors. Twenty-five
      farmworkers participated in in-depth interviews in which they described their
      households' food security situation and coping strategies. RESULTS: Forty-eight
      of the 102 sample households (47.1%) were classified as food insecure, including
      10 (9.8%) with moderate hunger and five (4.9%) with severe hunger. Households
      with children had a significantly higher prevalence of food insecurity than those
      without children (56.4% vs. 36.2%). Households with children accessed food
      programs such as the Special Supplemental Nutrition Program for Women, Infants
      and Children (WIC) that were unavailable to those without children, while those
      without children were more likely to access food pantries and to consume wild
      game or fish. Coping strategies included borrowing money, reducing food variety,
      and adults consuming less food to protect children from hunger. Food insecurity
      was more than four times as prevalent among farmworker households as among the
      general U.S. population. CONCLUSION: Policy changes to increase economic
      resources and access to federal programs are needed to decrease this food
      insecurity.

PMID- 15504450
TI  - State laws permitting intoxication exclusions in insurance contracts:
      implications for public health policy and practice.

PMID- 15504452
TI  - The CARE Communities project: an academic, practitioner, and federal public
      health agency collaboration to improve intimate partner violence services for
      underserved communities.

PMID- 15504453
TI  - Effect of Group 13 metals on porphobilinogen synthase in vitro.
AB  - Mammalian porphobilinogen synthase (PBGS) is a metalloenzyme, which requires Zn2+
      and reduced thiol groups for maximal catalytic activity, and is an important
      molecular target for the widespread environmental toxic metals. The mechanism
      underlying the PBGS inhibition by elements of Group 13 metals (Al3+, Ga3+, In3+,
      and Tl3+) has not yet been determined. The main objective of the present study
      was to characterize, in a comparative way, the molecular mechanism of PBGS
      inhibition caused by salts of elements of Group 13. Al3+, Ga3+, and In(3+i)
      inhibited purified hepatic bovine PBGS, and the IC50 for PBGS inhibition by Ga3+
      (IC50 = 442 +/- 63 micromol l(-1)) was higher than that for Al3+ (IC50 = 319 +/-
      41 micromol l(-1)) and In3+ (IC50 = 298 +/- 44 micromol l(-1)). Zn2+ restored
      completely aluminum-induced inhibitory effect on PBGS activity. Tl3+ inhibited
      liver bovine PBGS (IC50 = 8.5 +/- 0.9 micromol l(-1)) and glutathione reduced
      markedly this inhibitory effect (IC50 = 87 +/- 8 micromol l(-1)). GSH had no
      protective effects on the inhibitory actions of Al3+ and Ga3+ against PBGS; in
      contrast, GSH reduced the inhibitory effect of In3+ on PBGS. DL-dithiothreitol
      (DTT) restored completely the enzyme activity inhibited by Tl3+ and had only a
      modest effect on the inhibitory effect of In3+. Zn2+ was unable to change the
      inhibitory effect of Tl3+ on liver bovine PBGS; in contrast, Zn2+ recovered
      almost completely the enzyme inhibition caused by In3+ and Ga3+. Thus, our
      results indicated that Al3+, Ga3+, and In3+ inhibit PBGS by competing with Zn2+,
      whereas Tl3+ and In3+ inhibit bovine PBGS by directly oxidizing essential
      sulfhydryl groups.

PMID- 15504449
TI  - Evaluating the performance of the Centers for Disease Control and Prevention core
      Health-Related Quality of Life scale with adolescents.
AB  - OBJECTIVE: The purpose of this study was to evaluate the performance of the
      Centers for Disease Control and Prevention's core Health-Related Quality of Life
      (HRQOL) scale using data from 5,520 public high school students. METHODS: The
      1997 South Carolina Youth Risk Behavior Survey was the source of data. Chi-square
      analysis was applied to assess scale construct validity. Adjusted multiple
      logistic regression with selected tobacco and substance use variables was used to
      assess known-groups validity of the scale's Healthy Days index (items regarding
      poor physical and mental health days during the past 30 days). RESULTS: Construct
      validity was supported for the core HRQOL scale by the associations between self
      perceived health and physical health, mental health, and activity limitation
      days. A greater number of poor physical health days, poor mental health days, or
      activity limitation days was associated with poorer self-perceived health
      (p<0.0001); however, correlation coefficients for the associations between self
      perceived health and physical health days (r=0.24; p<0.001), self-perceived
      health and mental health days (r=0.26; p<0.0001), and self-perceived health and
      activity limitation days (r=0.23; p<0.0001), although significant, were low in
      magnitude. Logistic regression analyses conducted with the Healthy Days index
      revealed significant (p<0.05) HRQOL differences between users and non- users of
      tobacco and other substance use variables. As hypothesized, as the usage of each
      substance increased, reported poor HRQOL days increased, supporting the known-
      groups validity of the scale. CONCLUSIONS: This study provides preliminary
      evidence that the HRQOL scale items are valid and potentially useful for
      adolescent surveillance. The results, however, are mixed regarding the inclusion
      of self-perceived health as a measure of HRQOL for adolescents, given the low
      correlation coefficients for the associations between self-perceived health and
      the other HRQOL scale items. These results suggest that adolescents may be rating
      two separate dimensions of health when rating their self-perceived health and
      HRQOL. Further research is needed to confirm these findings in different
      adolescent populations.

PMID- 15504454
TI  - Roles of mitogen activated protein kinases and EGF receptor in arsenite
      stimulated matrix metalloproteinase-9 production.
AB  - The dermatotoxicity of arsenic is well established and epidemiological studies
      identify an increased incidence of keratinocytic tumors (basal cell and squamous
      cell carcinoma) associated with arsenic exposure. Little is known about the
      underlying mechanisms of arsenic-mediated skin carcinogenesis, but activation of
      mitogen-activated protein (MAP) kinases and subsequent regulation of downstream
      target genes may contribute to tumor promotion and progression. In this study, we
      investigated activation of the extracellular signal regulated kinase (ERK) and
      the stress-associated kinase p38 by arsenite in HaCat cells, a spontaneously
      immortalized human keratinocyte cell line. Arsenite concentrations > or =100
      microM stimulate rapid activation of p38 and ERK MAP kinases. However, upon
      extended exposure (24 h), persistent stimulation of p38 and ERK MAP kinases was
      detected at low micromolar concentrations of arsenite. Although ERK and p38 were
      activated with similar time and concentration dependence, the mechanism of
      activation differed for these two MAP kinases. ERK activation by arsenite was
      fully dependent on the catalytic activity of the epidermal growth factor (EGF)
      receptor and partially dependent on Src-family kinase activity. In contrast, p38
      activation was independent of EGF receptor or Src-family kinase activity.
      Arsenite-stimulated MAP kinase signal transduction resulted in increased
      production of matrix metalloproteinase (MMP)-9, an AP-1 regulated gene product.
      MMP-9 induction by arsenite was prevented when EGF receptor or MAP kinase
      signaling was inhibited. These studies indicate that EGF receptor activation is a
      component of arsenite-mediated signal transduction and gene expression in
      keratinocytes and that low micromolar concentrations of arsenite stimulate key
      signaling pathways upon extended exposure. Stimulation of MAP kinase cascades by
      arsenic and subsequent regulation of genes including c-fos, c-jun, and the matrix
      degrading proteases may play an important role in arsenic-induced skin
      carcinogenesis.

PMID- 15504455
TI  - Adjuvant activity of ambient particulate matter of different sites, sizes, and
      seasons in a respiratory allergy mouse model.
AB  - In the framework of an EU project entitled, "Respiratory Allergy and Inflammation
      due to Ambient Particles (RAIAP)", various ambient particulate matter samples
      were tested for their adjuvant potency in an animal allergy model to ovalbumin.
      Coarse (2.5-10 microm) and fine (0.15-2.5 microm) particles were collected during
      the spring, summer, and winter in Rome, Oslo, Lodz, and Amsterdam. Coarse and
      fine particles were also collected near a seaside location in the Netherlands,
      where prevailing winds are westerly. These latter particles served as a control,
      with a minimum contribution by traffic. Ottawa dust (EHC-93) was used as a
      standard reference sample. Immunoglobulins (IgE, IgG1, and IgG2a),
      histopathological changes in the lung, cytokines, and the number of cells and
      their differentiation in lung lavages were used as effect parameters to study the
      adjuvant potency of these particles. The particles (3 mg/ml) were mixed with
      ovalbumin (0.4 mg/ml) and intranasally administered during the sensitization or
      the challenge phase. Intranasal administration of ovalbumin only induced very
      little antibody response, but introduced a minor inflammatory response in the
      lung or BAL during the sensitization and challenge phase. On the contrary, after
      coexposure to EHC-93 and ovalbumin, a major increase was found in immunoglobulin
      levels specific for ovalbumin, and a major inflammatory response in lung and BAL
      was induced. Coexposure to ovalbumin with 4 out of 12 collected PM samples (3
      mg/ml) resulted in an increase of mainly IgE and IgG1. The histopathological
      changes consisted of a small to severe peribronchial and perivascular
      inflammatory response, a hypertrophy of bronchiolar mucous cells and an increase
      in eosinophils and neutrophils in the BAL. Statistical evaluation of the above
      mentioned parameters showed associations with PMx (coarse and fine), site,
      season, season x PMx, season x site and (PMx) x site. In addition, adjuvant
      activity of the PMx can be ranked as Lodz > Rome = Amsterdam > Oslo. When the
      different seasons were compared for IgE, PM from winter was found more active
      compared to PM from spring and summer. Only for the histopathological lesions,
      statistically significant difference in effects was found between coarse and fine
      (coarse > fine). No associations were found between the endotoxin content and the
      biological effects parameters, although endotoxin was much more confined to the
      coarse fraction. In conclusion, PM, both coarse and fine, and from various
      geographic sites, was found to differ in adjuvant activity; furthermore, winter
      was found more active than spring and summer.

PMID- 15504456
TI  - Toxicity of Hypericum perforatum (St. John's wort) administered during pregnancy
      and lactation in rats.
AB  - The popularity of St. John's wort (Hypericum perforatum) for the treatment of
      depression is increasing and, in recent years, concerns about its use during
      pregnancy and breastfeeding have emerged. The purpose of this study was to
      investigate, in Wistar rats, the effects of a treatment with hypericum
      administered prenatally and during breastfeeding (from 2 weeks before mating to
      21 days after delivery). Two doses of the extract were chosen, 100 mg/kg per day,
      which, based on surface area, is comparable to the dose administered to humans,
      and 1000 mg/kg per day. A microscopical analysis of livers, kidneys, hearts,
      lungs, brains, and small bowels was performed. A severe damage was observed in
      the livers and kidneys of animals euthanized postnatally on days 0 and 21. The
      lesions were more severe with the higher dose and in animals that were breastfed
      for 21 days; however, an important renal and hepatic damage was evident also with
      the dose of 100 mg/kg per day. In addition, similar serious hepatic and renal
      lesions were evident also in animals that were exposed to hypericum only during
      breastfeeding. In particular, a focal hepatic damage, with vacuolization, lobular
      fibrosis, and disorganization of hepatic arrays was evident; in the kidney, a
      reduction in glomerular size, disappearance of Bowman's space, and hyaline
      tubular degeneration were found. The results obtained in this study indicate that
      further, appropriate histological studies should be performed in other animal
      species to better evaluate the safety of hypericum extracts taken during
      pregnancy and breastfeeding.

PMID- 15504457
TI  - Suppression in lung defense responses after bacterial infection in rats
      pretreated with different welding fumes.
AB  - Epidemiology suggests that inhalation of welding fumes increases the
      susceptibility to lung infection. The effects of chemically distinct welding
      fumes on lung defense responses after bacterial infection were compared. Fume was
      collected during gas metal arc (GMA) or flux-covered manual metal arc (MMA)
      welding using two consumable electrodes: stainless steel (SS) or mild steel (MS).
      The fumes were separated into water-soluble and -insoluble fractions. The GMA-SS
      and GMA-MS fumes were found to be relatively insoluble, whereas the MMA-SS was
      highly water soluble, with the soluble fraction comprised of 87% Cr and 11% Mn.
      On day 0, male Sprague-Dawley rats were intratracheally instilled with saline
      (vehicle control) or the different welding fumes (0.1 or 2 mg/rat). At day 3, the
      rats were intratracheally inoculated with 5 x 10(3) Listeria monocytogenes. On
      days 6, 8, and 10, left lungs were removed, homogenized, cultured overnight, and
      colony-forming units were counted to assess pulmonary bacterial clearance.
      Bronchoalveolar lavage (BAL) was performed on right lungs to recover phagocytes
      and BAL fluid to measure the production of nitric oxide (NO) and immunomodulatory
      cytokines, including tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-2,
      IL-6, and IL-10. In contrast to the GMA-SS, GMA-MS, and saline groups,
      pretreatment with the highly water soluble MMA-SS fume caused significant body
      weight loss, extensive lung damage, and a dramatic reduction in pulmonary
      clearance of L. monocytogenes after infection. NO concentrations in BAL fluid and
      lung immunostaining of inducible NO synthase were dramatically increased in rats
      pretreated with MMA-SS before and after infection. MMA-SS treatment caused a
      significant decrease in IL-2 and significant increases in TNF-alpha, IL-6, and IL
      10 after infection. In conclusion, pretreatment with MMA-SS increased production
      of NO and proinflammatory cytokines (TNF-alpha and IL-6) after infection, which
      are likely responsible for the elevation in lung inflammation and injury. In
      addition, MMA-SS treatment reduced IL-2 (involved in T cell proliferation) and
      enhanced IL-10 (involved in inhibiting macrophage function) after bacterial
      infection, which might result in a possible suppression in immune response and an
      increase in susceptibility to infection.

PMID- 15504458
TI  - In vivo bioluminescent monitoring of chemical toxicity using heme oxygenase
      luciferase transgenic mice.
AB  - Transgenic mice expressing the luciferase (luc) gene under the control of the
      heme oxygenase-1 promoter (Ho1) were used to measure the induction of heme
      oxygenase in response to known toxicants. Transgenic Ho1-luc expression was
      visualized in vivo using a low-light imaging system (IVIS). Ho1-luc activation
      was compared to Ho1-luc expression, HO1 protein levels, standard markers of
      toxicity, and histology. Male and female Ho1-luc transgenic mice were exposed to
      acute doses of cadmium chloride (CdCl2, 3.7 mg/kg), doxorubicin (15 mg/kg), and
      thioacetamide (300 mg/kg). These agents induced the expression of Ho1-luc in the
      liver and other tissues to varying degrees. The greatest increase in Ho1-luc
      activity was observed in the liver in response to CdCl2; intermediate responses
      were observed for doxorubicin and thioacetamide. Induction of the Ho1-luc
      transgene by these agents was similar to endogenous protein levels of heme
      oxygenase as assessed by Western blotting, and generally correlated with plasma
      levels of circulating enzymes reflecting hepatic or general tissue damage.
      Histopathology confirmed the toxic effects of CdCl2 on liver and kidney;
      doxorubicin on kidney, liver, and intestine; and thioacetamide on the liver.
      Tissue damage was much more pronounced than the luciferase expression following
      thioacetamide treatment when compared with tissue damage and bioluminescence of
      the other toxicants. Nevertheless, the induction of Ho1-luc expression following
      exposure to these agents suggests that the Ho1-luc transgenic mouse may prove
      useful as a model for in vivo screening of compounds that induce luciferase
      expression as a marker of toxicity.

PMID- 15504459
TI  - Synthesis and evaluations of pentahydroxylhexyl-L-cysteine and its dimer as
      chelating agents for cadmium or lead decorporation.
AB  - N-(2,3,4,5,6-pentahydroxylhexyl)-L-cysteine (4) and N,N'-di(2,3,4,5,6
      pentahydroxylhexyl)-L-cystine (5) were synthesized. As antagonists of cadmium or
      lead intoxication, they were found to be effective by oral administration on
      repeated exposure. The bioassay in vivo indicated that their cadmium-mobilizing
      potencies are significantly superior to those of N-acetyl-L-cysteine and their
      lead-mobilizing properties are equivalent to those of DL-penicillamine (DL-PA).
      The stability constants of the Cd-4 and Cd-5 complexes or Pb-4 and Pb-5 complexes
      were determined by use of pH titration. The membrane permeability of compounds 4
      and 5 was evaluated by transporting across the Caco-2 cell monolayer. The effect
      of compounds 4 and 5 on the concentrations of essential metal ions in the renal
      cortex is negligible in comparison with that of the group treated with lead only.
      The acute toxicity of compounds 4 was tested by oral gavage and the resulting
      LD50 value for both mice and rats is larger than 10 g kg(-1) bw. The cytogenetic
      effects of compound 4 were evaluated in the Ames assay, mouse bone marrow
      micronucleus test, and sperms shape abnormality assay, and all of them show the
      negative reactions.

PMID- 15504460
TI  - Statins induce apoptosis in rat and human myotube cultures by inhibiting protein
      geranylgeranylation but not ubiquinone.
AB  - Statins are widely used to treat lipid disorders. These drugs are safe and well
      tolerated; however, in <1% of patients, myopathy and/or rhabdomyolysis can
      develop. To better understand the mechanism of statin-induced myopathy, we
      examined the ability of structurally distinct statins to induce apoptosis in an
      optimized rat myotube model. Compound A (a lactone) and Cerivastatin (an open
      acid) induced apoptosis, as measured by TUNEL and active caspase 3 staining, in a
      concentration- and time-dependent manner. In contrast, an epimer of Compound A
      (Compound B) exhibited a much weaker apoptotic response. Statin-induced apoptosis
      was completely prevented by mevalonate or geranylgeraniol, but not by farnesol.
      Zaragozic acid A, a squalene synthase inhibitor, caused no apoptosis on its own
      and had no effect on Compound-A-induced myotoxicity, suggesting the apoptosis was
      not a result of cholesterol synthesis inhibition. The geranylgeranyl transferase
      inhibitors GGTI-2133 and GGTI-2147 caused apoptosis in myotubes; the farnesyl
      transferase inhibitor FTI-277 exhibited a much weaker effect. In addition, the
      prenylation of rap1a, a geranylgeranylated protein, was inhibited by Compound A
      in myotubes at concentrations that induced apoptosis. A similar statin-induced
      apoptosis profile was seen in human myotube cultures but primary rat hepatocytes
      were about 200-fold more resistant to statin-induced apoptosis. Although the
      statin-induced hepatotoxicity could be attenuated with mevalonate, no effect was
      found with either geranylgeraniol or farnesol. In studies assessing ubiquinone
      levels after statin treatment in rat and human myotubes, there was no correlation
      between ubiquinone levels and apoptosis. Taken together, these observations
      suggest that statins cause apoptosis in myotube cultures in part by inhibiting
      the geranylgeranylation of proteins, but not by suppressing ubiquinone
      concentration. Furthermore, the data from primary hepatocytes suggests a cell
      type differential sensitivity to statin-induced toxicity.

PMID- 15504461
TI  - Ultraviolet irradiation increases the sensitivity of cultured human skin cells to
      cadmium probably through the inhibition of metallothionein gene expression.
AB  - We previously developed an apparatus that can irradiate cultured cells with
      monochromatic ultraviolet (UV) rays to exactly assess the biological effects of
      UV components on mammalian cells. Using this device, we studied the effects of UV
      in and near the UVB region on the general as well as specific protein synthesis
      of the human skin-derived NB1RGB cells. We found that Cd-induced synthesis of
      metallothioneins (MTs), which are the proteins involved in the protection against
      heavy metals and oxidative stress, is inhibited by UV at 280 nm more extensively
      than total protein synthesis. Such an inhibition was observed when MTs were
      induced by different inducers such as Cd, Zn, and dexamethasone in three human
      cell lines, indicating that it is not an event specific to a certain inducer or a
      certain cell type. By contrast, UV at 300 or 320 nm showed only a marginal
      effect. UV at 280 nm was likely to block MT gene transcription because Cd-induced
      increase of MT mRNA was strongly inhibited by irradiation. Cd induction of 70-kDa
      heat shock protein mRNA was also inhibited by UV irradiation, suggesting that the
      expression of inducible genes are commonly sensitive to UV. Furthermore, we
      observed that the irradiation of UV at 280 nm renders NB1RGB cells extremely
      susceptible to Cd, probably due to the reduced MT synthesis. These observations
      strongly suggest that UV at 280 nm severely damages cellular inducible protective
      functions, warning us of a new risk of UV exposure.

PMID- 15504462
TI  - Soil physical changes and plant availability of Zn and Pb in a treatability test
      of phytostabilization.
AB  - A treatability test of phytostabilization was carried out on two soils sampled
      downstream a mining Italian area with Lolium italicum and Festuca arundinacea.
      Beside chemical content of Pb and Zn in aerial parts and in roots, also some
      physical parameters were determined at the end of the growth cycle of plants.
      Particle size distribution was analysed with a laser granulometer while cracking
      patterns and porosity were determined by means of image analysis. Compost, used
      at two rates (10%, and 30% v/v) in order to improve soil physical
      characteristics, always raised biomass with similar effects for both doses. The
      concentration of Pb and Zn in aerial parts and in roots of L. italicum and F.
      arundinacea decreased more than five times in presence of compost. A general lack
      of clear effects of both plants on soil physical parameters was noticed.
      Formation of more water stable aggregates, a rise of the area occupied by cracks,
      and new porosity formed by elongated and irregular pores were found in soil
      samples treated with compost.

PMID- 15504463
TI  - Heavy metal retention and partitioning in a large-scale soil-aquifer treatment
      (SAT) system used for wastewater reclamation.
AB  - Soil aquifer treatment (SAT) of wastewater relies on extensive biogeochemical
      processes in the soil and aquifer to achieve large-scale and economic reclamation
      of municipal effluents. Removal of trace metals from the wastewater is a prime
      objective in the operation, but the long-term sustainability of the adsorptive
      filtration capacity of the soils is an open question. Solid/solution partitioning
      (measured by the distribution coefficient, K(d)) and solid/solid partitioning
      (measured by selective sequential dissolution, SSD) of heavy metals were measured
      in soils sampled from active recharge basins in a wastewater reclamation plant
      and were compared to the adjacent pristine dune. K(d) values for the adsorption
      of Cu, Ni and Zn, measured in short-term adsorption experiments positively and
      significantly correlated with solution pH. Quantitative estimation of Cu, Ni and
      Zn adsorption on multi-sorbents indicated that surface adsorption and
      precipitation on Fe oxides and/or carbonate may be the major mechanisms of metal
      retention in these soils. SSD analyses of metal partitioning in soils exposed to
      approximately 20yr of effluent recharge showed that all solid-phase components,
      including the most stable 'residual' component, competed for and retained added
      Cu and Zn. Copper preferentially partitioned into the oxide component (32.0% of
      the soil-accumulated metal) while Zn preferentially partitioned into the
      carbonate component (51.6% of the soil-accumulated metal).

PMID- 15504464
TI  - H(2) production through anaerobic mixed culture: effect of batch S(0)/X(0) and
      shock loading in CSTR.
AB  - Biological production of H(2) has received considerable attention lately. The
      present study was undertaken to observe the effects of substrate/seeding ratios
      (S(0)/X(0)) on batch H(2) generation. The H(2)-producing seeding spores were
      obtained from the heat treatment (88 degrees C for 12h) of the compost from a
      grass composting facility. A dehydrated brewery mixture was used as feed
      substrate. The results indicate that the pattern of the cumulative H(2)
      production with time is similar to the growth curve with a typical lag,
      exponential and stationary phase; the results were successfully modeled with a
      modified Gompertz equation. It appears that maximum H(2) yield potential (27ml g(
      1)COD(added)) occurs at an S(0)/X(0) ratio of about 4, whereas the maximum
      specific H(2) yield (205ml g(-1) VSSd(-1)) occurs at approximately S(0)/X(0)=3.
      The S(0)/X(0) ratios higher than 4 would inhibit H(2) production. An attempt was
      made to waste a certain amount of reactor content and replaced it with fresh
      substrate in order to enhance H(2) production. After this medium replacement, the
      H(2) production was initially inhibited and the system then exhibited a long lag
      before it reached an active H(2) production stage. For a continuous-stirred tank
      reactor (CSTR) system, the results of replacing 25% of the reactor content
      indicate that there is still a lag time before a sudden increase in H(2)
      production after the addition of the new substrate feed. The major low molecular
      weight acids identified are HAc and HBu with total volatile acids of about 6000
      8000mg l(-1). The ratio of HAc/HBu in the present study is relatively constant
      (about 5) and appears not significantly affected by the medium replacement. The
      concentration of total alcohols is about 2000mg l(-1). All in all, the CSTR
      system is able to recover to its previous performance after such a dramatic 25%
      medium replacement.

PMID- 15504465
TI  - Investigation of Cr(VI) reduction in continuous-flow activated sludge systems.
AB  - The aim of this research was to investigate hexavalent chromium, Cr(VI),
      reduction by activated sludge and to evaluate the use of continuous-flow
      activated sludge systems for the treatment of Cr(VI)-containing wastewater. Three
      series of experiments were conducted using two parallel lab-scale activated
      sludge systems. During the first experiment, one system was used as a control,
      while the other received Cr(VI) concentrations equal to 0.5, 1, 3 and 5mg l(-1).
      For all concentrations added, approximately 40% of the added Cr(VI) was removed
      during the activated sludge process. Determination of chromium species in the
      dissolved and particulate phase revealed that the removed Cr(VI) was sorbed by
      the activated sludge flocs mainly as trivalent chromium, Cr(III), while the
      residual chromium in the dissolved phase was mainly detected as Cr(VI). Activated
      sludge ability to reduce Cr(VI) was independent of the acclimatization of biomass
      to Cr(VI) and it was not affected by the toxic effect of Cr(VI) on autotrophic
      and heterotrophic microorganisms. During the second experiment, both systems were
      operated under two different hydraulic residence time (theta equal to 20 and 28h)
      and three different initial organic substrate concentration (COD equal to 300,
      150 and 0mg l(-1)). Cr(VI) reduction was favored by an increase of theta, while
      it was limited by influent COD concentration. Finally, at the last experiment the
      effect of anoxic and anaerobic reactors on Cr(VI) reduction was investigated. It
      was observed that the use of an anoxic zone or an anaerobic-anoxic zone ahead of
      the aerobic reactor favored Cr(VI) reduction, increasing mean percentage Cr(VI)
      reduction to almost 80%.

PMID- 15504466
TI  - An evaluation of surfactant foam technology in remediation of contaminated soil.
AB  - Soil contamination is notoriously difficult to treat because the contaminants are
      often tightly bound to the soil particles. Conventional remediation technologies
      are becoming less popular due to the high treatment costs. This paper gives a
      comprehensive overview and evaluation of an emerging promising alternative,
      surfactant foam technology. Different from other approaches, surfactant foam
      technology may be designed either to remove contaminants or/and simultaneously
      act as an augmentation for the existing technologies such as pump-and-treat
      systems and bioremediation processes to improve the contaminant removal
      efficiency and cost effectiveness. Encouraging results were achieved from
      laboratory and field demonstrations. However, as an innovative technology, there
      are many factors to be investigated with the future development. Special
      attention is paid to the selection of the most appropriate foaming surfactant and
      surfactant concentration, which are critical to the success of the implementation
      of the remediation process and have significant effects on the treatment costs.
      Moreover, development of predictive mathematical models in for future research is
      helpful to optimize the remediation process.

PMID- 15504467
TI  - Simultaneous removal of chlorinated aromatic hydrocarbons, nitrate, and chromate
      using micellar-enhanced ultrafiltration.
AB  - Feasibility of micellar-enhanced ultrafiltration for the mixed waste that is
      consisted of chlorinated aromatic hydrocarbons, nitrate, and chromate was
      investigated using a cationic surfactant. The co-presence of nitrate and chromate
      did not significantly affect the removal of chlorobenzenes, and the co-presence
      of chlorobenzenes did not affect the removal of nitrate and chromate because
      chlorobenzenes were solubilized at the hydrophobic interior of the micelles by
      hydrophobic interaction, but nitrate and chromate were bound to the outer shell
      by electrostatic interaction. Micellar-enhanced ultrafiltration can be applied to
      treat the mixed wastes.

PMID- 15504468
TI  - The use of elemental sulphur as organic alternative to control pH during
      composting of olive mill wastes.
AB  - High values of pH may represent a limitation for the agricultural use of the
      composts, not only when used as soil-less substrate but also as soil amendment in
      high pH soils. The addition of elemental S during the maturation phase of the
      composting process was evaluated as suitable method to reduce pH of the composts
      under the organic agriculture regulations. A compost prepared with two phase
      olive mill waste (OMW) and sheep litter (SL) was used to study the effect of
      elemental sulphur addition on the pH of the composting mixture. Initially,
      different bench scale experiments were designed in order to study the influence
      of moisture, sulphur concentration, and incubation temperature on the sulphur
      oxidation rate and thus on the pH of the compost. A concentration of 0.5% in
      sulphur (dry weight basis) and moisture of 40% were proposed as the optimum
      conditions to decrease the compost pH by 1.1 units without increasing in EC to
      levels that may suppose a limitation for its agricultural use. Finally, these
      optimum experimental conditions found at bench scale were tested at full scale in
      a commercial composting plant treating the same organic materials by windrowing.
      The pH values of the composting mixture were reduced by one unit after 2 weeks
      following the addition of elemental S causing no negative effects on the final
      compost quality.

PMID- 15504469
TI  - Oxidation of TNT by photo-Fenton process.
AB  - A series of photo-Fenton reactions have been performed for the degradation of
      2,4,6-trinitrotoluene (TNT) in a 4.2-l reactor. The degradation reaction rate of
      TNT followed a pseudo-first-order behavior; and the rate constants for 2.4mW cm(
      2)UV only, 2.4mW cm(-2)UV/H(2)O(2), Fenton, photo-Fenton (2.4mW cm(-2)) and photo
      Fenton (4.7mW cm(-2)) were 0.002min(-1), 0.007min(-1), 0.014min(-1), 0.025min(-1)
      and 0.037min(-1), respectively. Increasing the intensity of UV light, and the
      concentrations of ferrous ions and hydrogen peroxide promoted the oxidation rate
      under the experimental conditions in this study. The weighting factor (f), the
      Fe(II)-promoted efficiency (r) and the promoted-UV light efficiency (p) were
      calculated to clarify their effects on the TNT oxidation. Moreover, the
      inhibition effect of hydroxyl radical was also observed in both Fenton and photo
      Fenton oxidation when the concentration of Fe(II) were higher than 2.88mM. Solid
      phase micro-extraction was first applied to the separation of the organic
      byproducts from TNT oxidation. GC/MS was employed to identify the byproducts
      during the Fenton and photo-Fenton oxidation of TNT. These compounds were
      clarified as 1,3,5-trinitrobenzene, 1-methyl-2,4-dinitrobenzene 2,5
      dinitrobenzoic acid and 1,3-dinitrobenzene. By these byproducts, the mechanisms
      of the methyl group oxidation, decarboxylation, aromatic ring breakage, and
      hydrolysis can be recognized and demonstrated. The pathway of TNT oxidation by
      photo-Fenton process was also proposed in this study.

PMID- 15504470
TI  - Determining the effectiveness of conventional and alternative coagulants through
      effective characterization schemes.
AB  - Polymeric forms of metal coagulants in water treatment have become increasingly
      used due to their wider availability and reduction in cost. These specialized
      coagulant forms and products are claimed by manufacturers to be superior to
      conventional coagulants in particulate and/or organic removal with inherent
      advantages of lower alkalinity consumption and lesser sludge production. However,
      due to their proprietary nature, little is known about their chemical
      composition. To determine and understand the effectiveness of these alternative
      coagulants, a comprehensive study was undertaken to characterize metal
      coagulants, and to comparatively evaluate them on a well-characterized source
      water. The objective of this study was to provide a scheme for utilities that
      could be employed as a screening process and a method of selecting an appropriate
      coagulant based on raw water characteristics and insight into the coagulatability
      of the source water. Characterizations of coagulants included: (i) active metal
      content, (ii) anion content, (iii) acidity, (iv) alkalinity consumption, (v)
      charge reversal by colloidal titration, and (vi) molecular weight determination.
      A total of five poly-aluminum chlorides (PACl), along with a conventional
      coagulant (aluminum sulfate or alum) were evaluated. Results show that through
      the characterization scheme, an effective coagulant (conventional versus
      alternative) and coagulant type (among various PACl) can be chosen before
      undertaking time-consuming bench or pilot-scale evaluation.

PMID- 15504471
TI  - Oxidative degradation of 2,4-xylidine by photosensitization with 2,4,6
      triphenylpyrylium: homogeneous and heterogeneous catalysis.
AB  - The possibility of using zeolites containing the 2,4,6-triphenylpyrylium cation
      as photocatalysts for the degradation of pollutants has been tested on aqueous
      xylidine (2,4-dimethylaniline) solutions as models for contaminated wastewaters.
      The influence of the photocatalyst and substrate concentrations on xylidine
      oxidation has been investigated in homogeneous solution, by performing a series
      of experiments chosen according to the experimental design methodology (Doehlert
      uniform array). The empirical models and the corresponding response surfaces
      obtained from data analysis have been used for simulating and predicting
      degradation efficiency. The results have shown that conversion increases with
      increasing amounts of photocatalyst and decreasing concentration of the model
      pollutant. The fluorescence of 2,4,6-triphenylpyrylium was quenched by xylidine
      with a rate constant k(q) of 3.1x10(9)M(-1)s(-1). This result suggests a direct
      electron transfer between the excited pyrylium salt and xylidine. Because of the
      limited stability of the photocatalyst in homogeneous media, a pyrylium
      containing Y-zeolite has been tested for the photocatalytic oxidation of xylidine
      under heterogeneous conditions. The results suggest that the supported catalyst
      has a much improved stability and that xylidine oxidation rates remain nearly
      constant during the whole reaction time. An additional advantage of the pyrylium
      containing zeolite photocatalyst is that it can be recycled and used for further
      experiments.

PMID- 15504472
TI  - Surface properties and catalytic performance of La(1-x)Sr(x)FeO(3) perovskite
      type oxides for methane combustion.
AB  - La(1-x)Sr(x)FeO(3) (x=0.0-1.0) perovskites were prepared and tested for the
      combustion of methane. X-ray diffraction (XRD) patterns revealed the presence of
      a single perovskite structure for substitutions 0x0.3, however Fe(2)O(3), SrCO(3)
      and SrFeO(3) phases were observed for substitutions x>0.3. The results of
      activity test indicate that with La(1-x)Sr(x)FeO(3) as the catalyst, the
      combustion of methane can take place at low temperatures around 400 degrees C.
      Partial substitution of La with Sr increases the activity and an optimal
      substitution fraction (x=0.5) exists in the La(1-x)Sr(x)FeO(3) catalysts.
      Catalyst activity can be well correlated to the product of the specific surface
      area and atomic ratio of Fe to La+Sr on the catalyst surface. Experimental
      results of O(2)-TPD and CH(4)-TPD in the range of 350-500 degrees C indicate that
      the amount of oxygen desorbed from the La(1-x)Sr(x)FeO(3) catalysts is far larger
      than that of methane. Therefore, it can be proposed that the catalytic oxidation
      of CH(4) over these catalysts proceeds with the surface reaction between CH(4) in
      the gas phase and the adsorbed O(2). Addition of water vapor or CO(2) to the feed
      inhibited catalyst activity, but the inhibition was reversible and became
      negligible at high reaction temperature.

PMID- 15504473
TI  - Evaluation of biosurfactants for crude oil contaminated soil washing.
AB  - An evaluation of the ability of aqueous biosurfactant solutions (aescin,
      lecithin, rhamnolipid, saponin and tannin) for possible applications in washing
      crude oil contaminated soil was carried out. The biosurfactants behaviour in soil
      water, water-oil and oil-soil systems (such as foaming, solubilization, sorption
      to soil, emulsification, surface and interfacial tension) was measured and
      compared with a well-known chemical surfactant (sodium dodecyl sulphate, SDS) at
      varying concentrations. Results showed that the biosurfactants were able to
      remove significant amount of crude oil from the contaminated soil at different
      solution concentrations for instance rhamnolipid and SDS removed up to 80% oil
      and lecithin about 42%. The performance of water alone in crude oil removal was
      equally as good as those of the other biosurfactants. Oil removal was due to
      mobilization, caused by the reduction of surface and interfacial tensions.
      Solubilization and emulsification effects in oil removal were negligible due to
      the low crude oil solubilization of 0.11%. Therefore, these studies suggest that
      knowledge of surfactants' behaviour across different systems is paramount before
      their use in the practical application of oil removal.

PMID- 15504474
TI  - Decomposition of trichloroethylene and 2,4-dichlorophenol by ozonation in several
      organic solvents.
AB  - The effects of chemical characteristics of organic solvents on the decomposition
      rate constants of undissociative trichloroethylene (TCE) and dissociative 2,4
      dichlorophenol (2,4-DCP) by ozonation were studied. The TCE and 2,4-DCP
      decomposition by ozonation in organic solvents followed to the first-order
      reaction kinetics with respect to TCE or 2,4-DCP concentration. The orders of the
      rate constants among organic solvents for undissociative TCE and dissociative 2,4
      DCP were different indicating that the ozonation rates for undissociative and
      dissociative compounds were dependent on the chemical property of organic
      solvent. The decomposition of undissociative TCE by ozonation was a simple
      electrophilic reaction, which was dependent on acceptor number (AN) of the
      solvent. On the other hand, the decomposition of dissociative 2,4-DCP was
      dependent on by the dissociation of the compounds and would be dependent on donor
      number (DN) of the solvent. Finally, TCE in acetic acid was transformed to
      chlorinated intermediates and chloride ion and then these intermediates were
      continuously oxidized to chlorine gas.

PMID- 15504475
TI  - Effects of experimental parameters on NF(3) decomposition fraction in an oxygen
      based RF plasma environment.
AB  - Clean procedure is one of the major emitters of perfluorinated compounds (PFCs)
      in semiconductor manufacturing. Nitrogen trifluoride (NF(3)) is increasingly the
      process gas of choice for eliminating PFC emissions. However, its toxic to human
      and similar global warming potential compared to most other PFCs made NF(3)
      warranted much more investigation. This study demonstrated a radio-frequency
      plasma system for decomposing NF(3). The effects of experimental parameters:
      input power, O(2)/NF(3) ratio, operational pressure and NF(3) feeding
      concentration on NF(3) decomposition fraction (eta(NF3)) and energy efficiency
      E(NF3) were examined in detail. The analytical results demonstrated that the
      NF(3) was almost completely decomposed (>99%) at input power=30W,
      [NF(3)](in)=1.0% and eta(NF3) increased with input power. However, adding O(2) to
      the system inhibited NF(3) decomposition and decreased E(NF3). Moreover, eta(NF3)
      and E(NF3), decreased with gradually increasing operational pressure. Notably,
      increasing the NF(3) feeding concentration increased molecule density, reducing
      eta(NF3), but increasing E(NF3). Furthermore, the products detected in the
      NF(3)/O(2)/Ar plasma system were NO(2), NO, N(2)O, SiF(4), N(2) and F(2).
      Potential reaction pathways in the oxygen-based NF(3) plasma environment were
      built-up and elucidated.

PMID- 15504476
TI  - An unconventional approach to studying the reaction kinetics of the Fenton's
      oxidation of 2,4-dichlorophenoxyacetic acid.
AB  - The Fenton's oxidation kinetics of herbicide 2,4-D at various [Fe(II)] and
      [H(2)O(2)] combinations was investigated and modelled through an unconventional
      approach. The reaction kinetics of 2,4-D degradation demonstrated a two-stage
      pattern of decay, where a very fast reactive stage was followed by a retardation
      stage due to the depletion of oxidants and to the competitive side-reactions of
      the intermediates (including 2,4-dichlorophenol, chlorohydroquinone and 2,6
      dichlororesorcinol). A model characterized by two newly established constants,
      the initial decay rate and the maximum oxidative capacity, was proposed and
      proven capable of describing the two-stage process, which cannot easily be
      described by conventional first- or second-order kinetics approaches.

PMID- 15504477
TI  - Removal of Cu(II) from aqueous solution in a fluidized-bed reactor.
AB  - In this study, a fluidized-bed reactor (FBR) was employed to treat copper
      containing wastewater by mean of copper precipitation on the surface of sand
      grains. The conditions for optimum copper removal efficiency were also
      investigated. This technology was controlled so as to keep supersaturation low to
      induce the nucleated precipitation of copper coating on the sand surface in an
      FBR. The effects of relevant parameters, such as the pH value, the molar ratio of
      [C(T)] to [Cu(2+)], hydraulic loading and the types of chemical reagents used,
      were examined. The experimental results indicated that 96% copper removal
      efficiency could be achieved when the influent copper concentration was 10mg l(
      1). The optimum chemical reagent was Na(2)CO(3); the molar ratio of
      [C(T)]/[Cu(2+)] was 2, and the optimal hydraulic loading was not be more than 25m
      h(-1). In addition, preventing homogeneous nucleation in the FBR was an important
      operation parameter. Homogeneous nucleation and molecular growth would lead to
      undesirable microparticle formation in the effluent. A good mixture of carbonate
      and copper in the presence of sand grains could reduce the level of homogeneous
      nucleation in the bottom of the reactor. Energy dispersive analysis (EDS) of X
      rays provided insight into the copper coating on the sand surface, and element
      analysis indicated the weight percentages of CuCO(3) and Cu(OH)(2) in
      precipitate.

PMID- 15504478
TI  - Degradation of calcium lignosulfonate using gamma-ray irradiation.
AB  - Gamma-ray irradiation was proven to be a promising means for the removal of
      calcium lignosulfonate (CaLS). At a dose rate of 55Gy min(-1), over 90% of CaLS
      was mineralized to CO(2), H(2)O and sulfates within 3-d irradiation. The
      degradation of CaLS with the initial CaLS concentrations ranging from 40 to 200mg
      l(-1) followed zero-order kinetics at the dose rates of 16-150Gy min(-1). The
      zero-order degradation rate constant was functionally related with irradiation
      dose rate. Experiments performed with or without addition of radical scavengers
      demonstrated that the role of *OH was predominant in CaLS degradation and the
      reductive species made minor contributions to CaLS degradation. Addition of
      appropriate amounts of H(2)O(2) significantly enhanced the mineralization of
      CaLS, e.g., addition of 10mM H(2)O(2) at a dose rate of 55Gy min(-1) elevated the
      mineralization rate constant by five times. The addition of Fenton's reagent to
      irradiated CaLS solutions facilitated the degradation of CaLS, but no obviously
      synergistic effect was observed.

PMID- 15504479
TI  - Ozonation of Cationic Red X-GRL in aqueous solution: degradation and mechanism.
AB  - Ozonation of the azo dye Cationic Red X-GRL was investigated in a bubble column
      reactor at varying operating parameters such as oxygen flow rate, temperature,
      initial Cationic Red X-GRL concentration, and pH. The conversion of dye increased
      with the increasing of pH and oxygen flow rate. As the reaction rate constant and
      the volumetric mass transfer coefficient increase while the ozone equilibrium
      concentration decreases with the temperature, there is a minimum conversion of
      dye at 25 degrees C. The increasing of initial dye concentration leads to a
      decreasing conversion of dye while the ozonation rate increases. The formation of
      intermediates and the variation of pH, TOC, and nitrate ion during ozonation were
      investigated by the use of some analytical instruments such as GC/MS, GC, and IC.
      The intermediates of weak organic acids lower the pH value of the solution. The
      probable degradation mechanism of the Cationic Red X-GRL in aqueous solution was
      deliberated with the aid of Molecular Orbital calculations. The N(12)-C(13) site
      in Cationic Red X-GRL, instead of the N(6)-N(7) site, is found to be the
      principal site for ozone cycloaddition in the degradation processes. During the
      degradation process, among the six nitrogen atoms of Cationic Red X-GRL, one is
      transferred into a nitrate ion, one is converted into an amine compound, and the
      remaining four are transformed into two molecules of nitrogen.

PMID- 15504480
TI  - Molecular study of concentrated copper pollutant with a compost.
AB  - Humic substance in compost contains various organic functional groups that can
      sorb metal ions through ionic force. This study used thermal treatment technology
      to concentrate copper in the heated residues while destroying the humic substance
      of copper-sorbed kitchen compost. Scanning electron microscopy (SEM) results show
      that copper clusters were formed in the heated residues. Information from both X
      ray diffraction (XRD) patterns and Cu K-edge X-ray absorption spectroscopy (XAS)
      spectrum indicates that about 30% of the doped Cu(II) was chemically reduced to
      Cu(I) and Cu(0) when the sample was heated at 500 and 900 degrees C for 2h. The
      XAS results indicate that after 500 degrees C thermal treatment, the loaded
      Cu(NO(3))(2) was transformed into CuO (ca. 54%), Cu (ca. 18%), Cu(OH)(2) (ca.
      15%), and Cu(2)O (ca.13%). Heating at 900 degrees C caused more transformation
      into elemental Cu probably due to more release of oxygen.

PMID- 15504481
TI  - Copper-ligand complex for the decolorization of synthetic dyes.
AB  - The reaction system containing Cu(II), hydrogen peroxide and D-arabinono-1,4
      lactone was found to be effective in the decolorization and reduction of toxicity
      of azo, thiazine-, triphenylmethane- and anthraquinone-based synthetic dyes. More
      than 85% decolorization was obtained with 100ppm Acridine Orange, Azure B,
      Chicago Sky Blue 6B, Crystal Violet, Evans Blue, Poly B-411, Reactive Blue 2,
      Reactive Blue 5, and Remazol Brilliant Blue R incubated for 24h in the presence
      of 10mM CuSO(4), 20mM D-arabinono-1,4-lactone and 80 mM H(2)O(2). The rate of
      decolorization was not affected by pH in the range of 3-9. The rapid
      decolorization was accompanied by a fast decomposition of H(2)O(2) in the
      reaction mixture and by a fast production of hydroxyl radicals.

PMID- 15504482
TI  - Cadmium accumulation in Allium schoenoprasum L. grown in an aqueous medium.
AB  - The ability of Allium schoenoprasum L. (chives) to accumulate and tolerate
      cadmium in aqueous Hoagland medium at 50microM and 250microM was tested under
      continuous growth or several successive harvests of shoots. After 28 days of
      continuous growth, chives accumulated the metal up to 0.2% and 0.5% of its dry
      weight, when grown in 50microM and 250microM, respectively. In experiments that
      the leaves were successively harvested every 16 days, there were no obvious
      stress symptoms after six harvests during a period of 96 days at 50microM Cd. At
      250microM, after 64 days and four harvests, inhibition of growth occurred. In
      each treatment, a total of 1.2g kg(-1) DW and 2.4g kg(-1) DW was accumulated in
      the leaves, respectively. Total SH compounds concentration in leaf was found
      significantly higher by 3 and 7.4 times in plants treated with Cd at 50microM and
      250microM in comparison to the control, respectively, while no difference in the
      concentration of glutathione (GSH+GSSG) was found. Thus, it is assumed that
      sulphur-containing compounds, yet unknown, are involved in defensive mechanisms
      against heavy metals in chives. The results presented, point to chives
      phytoremediation potential, but also on the potential risk in accumulation of
      heavy metals in a commonly edible plant.

PMID- 15504483
TI  - Adsorption capacity of powdered activated carbon for 3,5-dichlorophenol in
      activated sludge.
AB  - The objectives of this study were to evaluate the performance of powdered
      activated carbon treatment (PACT) process based on the adsorption capacity of
      powdered activated carbon (PAC) in activated sludge and the effect of dissolved
      organic substances in activated sludge on the adsorption capacity of PAC. The DCP
      adsorption capacity of three PACs originated from different raw materials (coal,
      soft coal and sawdust) in activated sludge were 29%, 34% and 17% of that of new
      PAC, respectively. The performance of PACT process for shock loading of 3,5
      dichlorophenol (3,5-DCP) was different among PACs in spite of the same adsorption
      capacity in new PAC. The performance of PACT process for removal of DCP is
      dependent not on the adsorption capacity of new PAC but on the adsorption
      capacity of PAC in the aeration tank. Dissolved organic matter (DOM) with
      molecular weight smaller than 50kDa did not affect the adsorption capacity of PAC
      for 3,5-DCP in the activated sludge reactor. DOM with molecular weight larger
      than 50kDa and biofilm developed on the surface of PAC seemed to be responsible
      for the decreased adsorption capacity of PAC for the DCP.

PMID- 15504484
TI  - Removal of nickel (II) from aqueous solutions using marine macroalgae as the
      sorbing biomass.
AB  - In the present study biosorption technique, the passive accumulation of metals by
      biomass, is used for the removal of nickel from aqueous medium. The brown algae,
      Sargassum sp., in its natural and acid treated forms are used as a low cost
      sorbent. The adsorption characteristics of nickel on Sargassum sp. are evaluated
      as a function of time, pH, adsorbent dosage and initial concentration of nickel.
      The equilibrium adsorption data are fitted to Freundlich and Langmuir adsorption
      isotherm models and the model parameters are evaluated. Both the models represent
      the experimental data satisfactorily. The adsorption follows Lagergren first
      order kinetic model. The monolayer adsorption capacities of natural and acid
      treated forms of algae as obtained from Langmuir adsorption model are found to be
      181 and 250mg g(-1) respectively.

PMID- 15504487
TI  - Key pollutants--airborne particles.
AB  - The sources and composition of airborne particles, and trends observed over the
      past 50 years are reviewed in this paper. Major components of recent samples
      include elemental and organic carbon, secondary ammonium sulphate and ammonium
      nitrate, resuspended dust, and soil and sodium chloride. Early measurements
      employed the black smoke technique. More recently, PM(10) has been the accepted
      measure and is the basis for air quality standards and limit values. Between 1970
      and 1999, a substantial reduction in emissions of particulate matter was achieved
      mainly through a cut in emissions from commercial, residential, and institutional
      combustion. Forthcoming European Union standards are likely to require
      particulate traps on new diesel vehicles.

PMID- 15504485
TI  - Effects of humic substances on the decomposition of 2,4-dichlorophenol by ozone
      after extraction from water into acetic acid through activated carbon.
AB  - The objectives of this study are to clarify the behavior of humic substances
      throughout the processes of 2,4-dichlorophenol (2,4-DCP) adsorption on granular
      activated carbon (GAC) from water and extraction into acetic acid, and the
      influence of the extracted humic substances on the decomposition of 2,4-DCP by
      ozone in the acetic acid. The adsorption capacity of GAC for 2,4-DCP was not
      influenced by the humic substances preloaded to have equilibrium concentration of
      24.9mg Cl(-1) (14.5mg Cg(-1)). The adsorption capacity of GAC for 2,4-DCP
      decreased to one tenth of new GAC after the first adsorption-extraction step
      because of only 16% desorption in the first step. However, 2,4-DCP adsorbed on
      GAC was completely extracted after the second step suggesting that GAC can be
      used as adsorbent to transfer 2,4-DCP from water to acetic acid. The
      concentration ratio of 2,4-DCP from water into acetic acid was around 2x10(5),
      whereas the concentration ratio of humic substances was about 3.5, indicating
      that 2,4-DCP was selectively adsorbed and extracted by this system. The first
      order degradation rate constant for 2,4-DCP by ozone in acetic acid increased
      with the addition of humic substances. The rate constant with 16mg Cl(-1) of
      humic substances was 2.6 times as high as that without humic substances. Humic
      substances behaved as a promoter for the degradation of 2,4-DCP by ozone.

PMID- 15504488
TI  - Key airborne pollutants--the impact on health.
AB  - Current appreciations of the effect on health of classical air pollutants
      including nitrogen dioxide, sulphur dioxide, particulate matter, carbon monoxide
      and ozone, depend upon modern techniques of epidemiological research. These
      techniques, which are powerful and able to detect small effects, depend upon the
      power of modern computers and, though the theory was understood, their
      application was not possible for most research workers before about 1980. The
      methods involve handling large data sets and the application of complex methods
      of regression analysis. Dealing statistically with the many confounding factors
      that obscure and interact with the effects on health of air pollutants is
      possible using these methods. Early concerns about the adequacy of handling
      confounding factors have recently been allayed. This review considers short-term
      impacts, long-term impacts and areas where further research is required.

PMID- 15504489
TI  - Air pollution and policy--1952-2002.
AB  - This review examines the main events, pressures and constraints in the evolution
      of air quality policy over the past 50 years. At the start of that period, there
      was little explicit recognition of air quality monitoring, modelling, control or
      policy; currently, the emphasis is on targets with implementation underpinned by
      legislation. The European Union and other international organisations exert
      strong influence. Data collection and information dissemination have had major
      impacts as has the involvement of stakeholders.

PMID- 15504490
TI  - Environmental routes for platinum group elements to biological materials--a
      review.
AB  - The increased use of platinum group elements (PGE) in automobile catalysts has
      led to concern over potential environmental and biological accumulation. Platinum
      (Pt), palladium (Pd) and rhodium (Rh) concentrations have increased in the
      environment since the introduction of automobile catalysts. This review
      summarises current knowledge concerning the environmental mobility, speciation
      and bioavailability of Pt, Pd and Rh. The greater proportion of PGE emissions is
      from automobile catalysts, in the form of nanometer-sized catalyst particles,
      which deposit on roadside surfaces, as evidenced in samples of road dust, grass
      and soil. In soil, PGE can be transformed into more mobile species through
      complexation with organic matter and can be solubilised in low pH rainwater.
      There are indications that environmentally formed Pd species are more soluble and
      hence more mobile in the environment than Rh and Pt. PGE can reach waterbodies
      through stormwater transport and deposition in sediments. Besides external
      contamination of grass close to roads, internal PGE uptake has been observed for
      plants growing on soil contaminated with automobile catalyst PGE. Fine particles
      of PGE were also detected on the surface of feathers sampled from passerines and
      raptors in their natural habitat, and internal organs of these birds also
      contained PGE. Uptake has been observed in sediment-dwelling invertebrates, and
      laboratory studies have shown an uptake of PGE in eel and fish exposed to water
      containing road dust. The available evidence indicates that the PGE, especially
      Pd, are transported to biological materials through deposition in roots by
      binding to sulphur-rich low molecular weight species in plants. PGE uptake to
      exposed animals have uptake rates in the following order: Pd>Pt>Rh. The liver and
      kidney accumulate the highest levels of PGE, especially Pd. Urinary Pd and Rh,
      but not Pt, levels are correlated with traffic intensity. Dental alloys may lead
      to elevated urinary Pt levels. Platinum is a well-known allergen and Pd also
      shows a strong sensitisation potential.

PMID- 15504491
TI  - Parking, energy consumption and air pollution.
AB  - This paper examines the impacts of different ways of parking on environmental
      effects, mainly vehicle emissions and air pollution. Vehicle energy consumption
      and the urban air quality at street level, related to location and design of
      parking establishments, need to be assessed and quantified. In addition, the
      indoor parking environment needs attention. This paper gives a description of a
      methodological approach when comparing different parking establishments. The
      paper also briefly describes a Swedish attempt to create methods and models for
      assessing and quantifying such problem. The models are the macrolevel model
      BRAHE, for regional traffic exhaust emission, and the micromodel SimPark, a
      parking search model attempt combined with emission models. Until now, very
      limited knowledge exists regarding the various aspects of vehicle parking and
      environmental effects in the technical field as well as in the social and human
      behaviour aspects. This requires an interdisciplinary approach to this
      challenging area for research, development and more directly practically
      implemented surveys and field studies. In order to illustrate the new evaluation
      methodology, the paper also contains some results from a pilot study in
      Stockholm. Given certain assumptions, a study of vehicle emissions from parking
      in an underground garage compared with kerbside parking has given an emission
      reduction of about 40% in favour of the parking garage. This study has been done
      using the models mentioned above.

PMID- 15504492
TI  - Managing the environmental impacts of land transport: integrating environmental
      analysis with urban planning.
AB  - Ecological systems have limits or thresholds that vary by pollutant type,
      emissions sources and the sensitivity of a given location. Human health can also
      indicate sensitivity. Good environmental management requires any problem to be
      defined to obtain efficient and effective solutions. Cities are where transport
      activities, effects and resource management decisions are often most focussed.
      The New Zealand Ministry of Transport has developed two environmental management
      tools. The Vehicle Fleet Model (VFM) is a predictive database of the
      environmental performance of the New Zealand traffic fleet (and rail fleet). It
      calculates indices of local air quality, stormwater, and greenhouse gases
      emissions. The second is an analytical process based on Environmental Capacity
      Analysis (ECA). Information on local traffic is combined with environmental
      performance data from the Vehicle Fleet Model. This can be integrated within a
      live, geo-spatially defined analysis of the overall environmental effects within
      a defined local area. Variations in urban form and activity (traffic and other)
      that contribute to environmental effects can be tracked. This enables analysis of
      a range of mitigation strategies that may contribute, now or in the future, to
      maintaining environmental thresholds or meeting targets. A case study of the
      application of this approach was conducted within Waitakere City. The focus was
      on improving the understanding of the relative significance of stormwater
      contaminants derived from land transport.

PMID- 15504493
TI  - An evaluation of particle deposition fluxes to cultural heritage sites in
      Florence, Italy.
AB  - The pernicious effects of deposition of airborne particles on monumental stones
      have been widely demonstrated, but estimates of deposition fluxes on historic
      buildings remain a hard task because of the lack of careful experiments and
      modelling. AERBOX is a new box model developed by ENVIROWARE and ENEA, simulating
      the whole life cycle of aerosols. AERBOX takes into account all the relevant
      chemical and physical processes involved: emission, chemical reactions in gas and
      in gas-liquid phases, deposition, entrainment, condensation and nucleation.
      Concentration and deposition rates of 52 species of gaseous pollutants and 14
      species of particulate pollutants are calculated on hourly basis. A modelling
      system composed by AERBOX and the emission pre-processor Tool for Hourly
      Speciation of CORINAIR Annual Emissions (THOSCANE) has been applied to estimate
      the flux of particulate matter deposited on the monumental area of Florence
      downtown starting from a CORINAIR emission inventory developed by the Tuscany
      Region including the industrial and mobile sources in the area of Florence and
      Prato counties. The time and chemical profiles of the emissions have been adapted
      to the Tuscany region from the reference profiles given by both the California
      Air Resource Board and EPA and meteorological inputs were given by the Tuscany
      Meteorological Centre. Concentrations and deposition fluxes were compared with
      field measurements available in the open literature.

PMID- 15504494
TI  - The ARTEMIS European driving cycles for measuring car pollutant emissions.
AB  - In the past 10 years, various work has been undertaken to collect data on the
      actual driving of European cars and to derive representative real-world driving
      cycles. A compilation and synthesis of this work is provided in this paper. In
      the frame of the European research project: ARTEMIS, this work has been
      considered to derive a set of reference driving cycles. The main objectives were
      as follows: to derive a common set of reference real-world driving cycles to be
      used in the frame of the ARTEMIS project but also in the frame of on-going
      national campaigns of pollutant emission measurements, to ensure the
      compatibility and integration of all the resulting emission data in the European
      systems of emission inventory; to ensure and validate the representativity of the
      database and driving cycles by comparing and taking into account all the
      available data regarding driving conditions; to include in three real-world
      driving cycles (urban, rural road and motorway) the diversity of the observed
      driving conditions, within sub-cycles allowing a disaggregation of the emissions
      according to more specific driving conditions (congested and free-flow urban).
      Such driving cycles present a real advantage as they are derived from a large
      database, using a methodology that was widely discussed and approved. In the
      main, these ARTEMIS driving cycles were designed using the available data, and
      the method of analysis was based to some extent on previous work. Specific steps
      were implemented. The study includes characterisation of driving conditions and
      vehicle uses. Starting conditions and gearbox use are also taken into account.

PMID- 15504495
TI  - Characterisation of an urban bus network for environmental purposes.
AB  - Since pollutant emissions are closely related to the operating conditions of
      vehicles, their evaluation usually involves studying these operating conditions
      (through bus instrumentation and monitoring under actual operation), the design
      of representative driving or engine test cycles and the measurement of pollutant
      emissions. A preliminary characterisation of the routes on a bus network should
      make it possible to identify typical routes, the driving conditions and pollutant
      emissions of which are then studied. Two approaches are envisaged and applied to
      the Paris area, for which a wealth of information is available, which should be
      transferable to other bus networks. Both approaches are based on factorial
      analysis and automatic clustering, to allow optimum description and the
      identification of a pertinent typology of the bus routes in several classes. The
      first attempt at characterisation is based on statistics relating to bus
      operations: route characteristics (length, dedicated bus lanes, number of stops,
      location of stops: schools, tourist sites, hospitals, railways or underground
      stations), travel time, commercial speed, annual statistics (number of
      passengers, number of vehicles per hour, total kilometres), the irregularity of
      travel (variation of travel times, injuries, congestion.), as well as information
      on the problems encountered (congestion, distribution of the passenger load,
      junctions, bends). A second approach is based on the analysis of the "urban
      context" in which buses are driven. Population, employment, housing, road
      network, traffic and places that generate or disturb traffic (schools, railway
      stations, shopping areas, etc.) are calculated for the Ile de France region, by
      cells of 100 x 100 m, and collected in a geographical information system (GIS).
      Statistical analyses enable a typology of these urban cells to be established,
      the main parameters being density, type of housing, road types and traffic
      levels. The bus routes are then analysed according to their itineraries across
      these typical areas (distances travelled in each type of area) using a similar
      approach. A comparison of the typologies obtained from operational data and from
      urban data highlights the advantages and disadvantages of the two approaches. The
      first result from these typologies is the selection of routes which are
      representative of the different classes, in order to instrument buses and record
      driving patterns. This method should also make it possible to link driving
      conditions and urban characteristics, and then to allocate pollutant emission
      factors to given geographical situations, in particular, in the context of
      emission inventories or impact studies.

PMID- 15504496
TI  - A structured methodology to calculate traffic emissions inventories for city
      centres.
AB  - This study presents a methodology to estimate traffic emissions inventories for
      the case of city centres. It deals with the problem in a structured manner,
      identifying the sources and the formats of the input data as well as labelling
      the steps needed to perform the calculation. It describes a method to calculate
      the total mileage driven around the city using the concept of mileage per zone.
      Although the methodology employs a classical approach through the use of emission
      factors developed for mean speeds, it also discusses the possibility of applying
      these factors to instantaneous speeds. Finally, the study focuses on the
      influence of two critical factors: time resolution and the estimate of the total
      mileage. In both cases, the results indicate that the assumptions made are
      adequate and yield accurate results. The methodology has been applied to the city
      of Madrid as an example.

PMID- 15504497
TI  - Influence of traffic on the PM10 and PM2.5 urban aerosol fractions in Madrid
      (Spain).
AB  - A preliminary assessment carried out in Madrid demonstrates the difficulty of
      compliance with the new European PM(10) tolerances. Daily and annual limiting
      values would be exceeded at almost all the network stations under the terms of
      the directive's second stage. An experimental study, based on the chemical
      characterisation of the PM(10) and PM(2.5) fractions sampled at a representative
      urban site, provides the major mass contents of these two fractions. These are
      mainly related to two different particle sources: combustion processes including
      traffic emissions and mineral-origin particles. Nonmineral carbon is the major
      component of particulate matter in this region, mostly in the PM(2.5) fraction,
      increasing its contribution in wintertime. The second largest component
      identified in the PM(10) mass, is associated with crustal origin particles and is
      more relevant in summer, whereas the second largest contributor to PM(2.5) is
      secondary particles. In general, PM(10) and PM(2.5) concentrations show good
      agreement with traffic-related pollutants, such as nitrogen oxides and CO, being
      time-correlated in winter pollution episodes. PM(1) and PM(2.5) have been
      simultaneous and continuously measured indicating road transport as the main
      source of these finer fractions. Mineral contribution has been mainly identified
      in the coarser particles associated with dust resuspension and some long-range
      transport events of Saharan dust, although they are also present in the finer
      PM(2.5) fraction.

PMID- 15504498
TI  - Ammonia, nitrous oxide and hydrogen cyanide emissions from five passenger
      vehicles.
AB  - In this paper, three unregulated components, ammonia, nitrous oxide and hydrogen
      cyanide, emitted from five passenger vehicles are investigated. With focus upon
      emission factors from existing production technology, vehicles produced between
      1989 and 1998 with considerable mileage (7000 to 280,000) are chosen. Among the
      five vehicles, four were sold in the European market, whereas one was sold in the
      US market. The vehicles are tested on a chassis dynamometer. An EU2000 Driving
      Cycle (NEDC) and a US Urban Driving Cycle (UDC) of the Federal Test Procedure 75
      (FTP-75) are used in the study. The regulated emissions are measured using a
      Horiba Mexa series. Unregulated emissions, ammonia (NH(3)), nitrous oxide (N(2)O)
      and hydrogen cyanide (HCN) are analysed by mass spectrometer, gas chromatography
      and CNT-NA, TIM315-74W method, respectively. Both the unregulated emissions and
      the regulated emissions show driving cycle dependency; and they are also improved
      with newer vehicle and emission control technology. However, a gasoline direct
      injection vehicle (relatively new technology in this study) has rather high
      regulated emissions, whereas the NH(3), N(2)O and HCN emissions are low.

PMID- 15504499
TI  - Comparison between experimental and calculated vehicle idle emission factors for
      Madrid fleet.
AB  - Experimental vehicle idle emission factors have been compared with calculated
      factors for 100 vehicles in Madrid. The vehicles were selected according to the
      distribution (by age and fuel type) of the official, national car fleet (up to 31
      December 1997). They were then clustered following the criteria of the Computer
      Programme to Calculate Emissions from Road Transport (COPERT III) category
      classification. NO(x) and CO idle emission factors show a wide range of values in
      each category and an important deviation between the experimental values and the
      corresponding parameterised ones. Fifteen percent of tested vehicles in this
      study have been identified as gross emitters generating approximately 50% of the
      total CO emission volume.

PMID- 15504500
TI  - A combined chemical and bioassay analysis of traffic-emitted polycyclic aromatic
      hydrocarbons.
AB  - The objective of this study was to determine the concentrations of an extended
      series of polycyclic aromatic hydrocarbons (PAHs) and nitrated PAHs in outdoor
      air samples collected in low-contaminated urban areas, affected mainly by traffic
      emissions, and to estimate in vitro mutagenic and dioxin-like toxicity of
      extracts from these samples. Data on concentrations of PAHs and toxic in vitro
      potencies were compared in extracts obtained by different sampling methods. PAHs
      and their derivatives were analysed by high performance liquid chromatography
      with diode array and fluorescence detection, as well as gas chromatography with
      mass spectrometry. The total sum of 39 PAHs under study ranged from 6.7 to 62.7
      ng.m(-3); of this, the sum of 16 U.S. EPA priority PAHs in urban air samples
      ranged from 3.2 to 6.2 ng.m(-3). Phenanthrene was the prevalent PAH in all air
      samples tested, with concentrations up to 17.6 ng.m(-3), followed by fluorene,
      fluoranthene and pyrene present mostly in the gaseous phase. Also, other low
      molecular weight PAHs (with MW up to 228) were distributed mostly in gaseous
      phase. The particulate phase contained mostly carcinogenic PAHs, among which,
      benzo[a]pyrene, indeno[1,2,3-cd]pyrene and benzofluoranthenes were predominant
      compounds (with benzo[a]pyrene reaching levels up to 1.57 ng.m(-3)). Traffic
      emissions were confirmed as the major source of PAHs in the airborne samples due
      to the presence of elevated concentrations of benzo[ghi]perylene and coronene.
      The most abundant nitrated PAH derivatives were nitronaphthalenes, which were
      present exclusively in the vapor phase; 9-nitroanthracene, 9-nitrophenantrene and
      3-nitrofluoranthene were associated mostly with particulate matter (PM(10)).
      Bioassays for detection of the Ah receptor-mediated activity and mutagenicity in
      vitro were used as a screen of potential adverse effects of air pollutants
      emitted from traffic. The major part of mutagenic and aryl hydrocarbon receptor
      (AhR)-mediated activities was found to be present in the PM(10) fraction.
      Although the PM(10) sampling technique was found to be a suitable method
      regarding the subsequent determination of mutagenic and AhR-mediated activities
      in vitro, relative toxic potencies, associated with low molecular weight PAHs
      (such as tumor promotion and other adverse effects), could be underestimated.

PMID- 15504502
TI  - Heavy metal removal from motorway stormwater using zeolites.
AB  - The possibility of using zeolites to reduce the levels of heavy metals present in
      motorway stormwater has been investigated. Currently, the primary pollutant
      removal mechanism used in treating stormwater is retaining the large volume of
      stormwater in detention ponds to allow time for the contaminants (mainly those
      associated with particulate matter) to separate out. There is also a need to
      reduce the levels of heavy metals in the dissolved phase, possibly by introducing
      some kind of ion exchange material into the treatment facility. Batch experiments
      have been conducted on two zeolites (synthetic MAP and natural mordenite) to test
      their ability to remove dissolved heavy metals from simulated and spiked motorway
      stormwater. Synthetic zeolite MAP showed almost complete removal (>91%) of the
      studied heavy metals (Zn, Cu, Pb, Cd) from both solutions. However, the use of
      such synthetic zeolites could have serious environmental implications as it was
      found to increase sodium levels to 295 mg/l, remove calcium and increase the pH
      of the spiked motorway stormwater to 8.5. Mordenite was less effective at
      reducing the levels of heavy metals (42-89% in synthetic solution, 6-44% in
      motorway stormwater) and exhibited a preference for Pb>Cu>Zn approximately Cd. It
      is proposed that the uptake of heavy metals is partially inhibited by the other
      dissolved contaminants present in motorway stormwater.

PMID- 15504501
TI  - Platinum group elements in raptor eggs, faeces, blood, liver and kidney.
AB  - The increased use of platinum group elements (PGEs) in automobile catalysts and
      their emission into the environment has led to a concern over environmental and
      particularly biological accumulation. Specimens of samples from raptors are
      useful for the investigation of the impact of PGEs because these birds are found
      in both urban and rural environments and are invariably at the top of the food
      chain. Platinum (Pt), palladium (Pd) and rhodium (Rh) concentrations were
      determined by quadrupole Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) in
      eggs of the sparrowhawk (Accipiter nisus) and the peregrine falcon (Falco
      peregrinus), and in blood, liver and kidney of the peregrine falcon, while only
      Pt was determined in faeces of the peregrine falcon and the gyrfalcon (Falco
      rusticolus). PGE concentrations were higher in blood compared to both faeces and
      eggs, while liver and kidney concentrations were not elevated indicating no
      bioaccumulation through metallothionein pathways. A significant spatial trend
      could only be established for Pt in faeces. The general lack of a spatial trend
      is probably due to the widespread distribution of automobiles and the long-range
      transport of nanoparticles containing PGEs, and because birds migrate and forage
      over large areas. No significant temporal trend could be established. Higher
      relative concentrations of Pd, followed by Rh and Pt, indicate a mobility
      gradient of Pd>>Rh>Pt.

PMID- 15504503
TI  - C1 to C9 volatile organic compound measurements in urban air.
AB  - Urban atmospheric samples were collected in A Coruna (NW Spain) and analysed for
      volatile organic compounds. One hundred and twenty one hour samples were
      collected in winter 2000. The ambient air was rich in benzene, toluene, ethyl
      benzene and xylenes (BTEX) and especially toluene (mean: 23.6 microg m(-3),
      median: 14.66 microg m(-3)), but the presence of chlorinated compounds was also
      notable. High concentrations of 1,4-dichlorobenzene (mean: 11.4 microg m(-3),
      max: 90.4 microg m(-3)) were recorded. Multivariate analysis of VOC, trace gases
      (NO(x), NO(2), NO, SO(2) and O(3)) and meteorological variables (temperature,
      wind direction and speed, precipitation and radiation) was applied and
      correlations between VOC were also studied. Principal component analysis and
      correlation analysis confirm traffic as the main source of VOC in the area,
      although the importance of evaporative sources is also reflected. Three groups of
      samples were obtained by cluster analysis; these groups are formed depending on
      the content of aromatics and ozone and, in many cases, on the sampling hour.

PMID- 15504504
TI  - The impact of reduction in the benzene limit value in gasoline on airborne
      benzene, toluene and xylenes levels.
AB  - Background benzene, toluene, xylenes (BTX) average concentrations have been
      measured over the urban agglomeration of Toulouse, France, during both springtime
      and summer periods of 1999 and 2001. The benzene average amount over the two
      Toulouse campaigns in 1999 is equal to 2.2 microg/m(3), very close to the French
      air quality standard and well under the average value of 5 microg/m(3)
      recommended by European Economic Community countries, recognising that those
      regulations are given for a whole year. BTX pollution over Toulouse has, in
      particular, been produced by motor vehicle exhaust gases. For the study conducted
      during the same periods of 2001, benzene concentrations were within the French
      quality value in the whole area. This is because the benzene limit value
      contained in gasoline went from 5% to 1% since 2000 January 1. It will be
      important to measure benzene over annual periods in order to know its exact
      values over such a period and to observe its potential seasonal variations.

PMID- 15504505
TI  - A comparison of measurements and CFD model predictions for pollutant dispersion
      in cities.
AB  - An accurate description of car movements in an urban area is required for
      accurate prediction of the air pollution concentration field. A 3-D Eulerian
      Lagrangian approach to moving vehicles that takes into account the traffic
      induced flow field and turbulence is presented. The approach is based on
      Computational Fluid Dynamics (CFD) calculations using Eulerian approach to the
      continuous phase and Lagrangian approach to the discrete phase of moving objects
      vehicles. In the first part of the present contribution, the method is applied to
      pollutants dispersion in a city tunnel outlet in Brno and to a street structure
      in Hannover, Germany. In the second part, a model of traffic dynamics inside a
      street intersection in the centre of Brno is presented. This model accounts for
      the dynamics of traffic lights and a corresponding traffic-generated flow field
      and emissions in different time intervals during the traffic light sequence. All
      results of numerical modelling are compared with field measurements with very
      good agreement. A commercial CFD code StarCD was used into which the Lagrangian
      model and traffic dynamics model were integrated.

PMID- 15504506
TI  - A Lagrangian model of the evolution of the particulate size distribution of
      vehicular emissions.
AB  - The emission inventory for London indicates that nearly 80% of the particulate
      emissions derive from vehicular sources. Most of this mass is in the form of
      ultrafine submicrometer particles which are of concern because of their influence
      on lung function. The prediction of their dispersion in the atmosphere coupled to
      the physical and chemical transformations which affect their size distribution
      and concentration are of great importance. This paper reports the first results
      from a new meso-scale Lagrangian model which follows the particulate emissions
      and the evolution of their size distribution across the city. The vehicular
      emissions are based on the published inventory, corrected to time of day, while
      other emissions are assumed steady. The initial size distributions of background
      and emitted particles are represented by the sum of three lognormal
      distributions. Meteorological data are derived from Meteorological Office reports
      and are preprocessed to obtain the hourly values of boundary layer depth, Monin
      Obukov (MO) length, friction velocity, etc., needed for the computation of the
      vertical dispersion process via eddy diffusivities and the aerodynamic component
      of the dry deposition process. In the vertical direction, three layers are
      assumed-surface layer (typically 50 m), canopy layer and one further layer up to
      the prevailing boundary layer depth. Currently, the model includes wet and dry
      deposition and coagulation but not chemical reaction, nucleation or
      deliquescence. Trajectories are evolved for several hours across the city and the
      number size distributions and mass concentrations (PM10, PM2.5, PM1 and PM0.1)
      output at each step. This enables the vehicular contributions over and above the
      background concentration in each size range to be studied in detail. Data from
      the model have been compared with experimental data for one of the London
      background sites where particle number size distribution up to 450 nm (SMPS),
      plus PM10 and PM2.5 (TEOM) data are available.

PMID- 15504507
TI  - The boundary layer growth in an urban area.
AB  - The development and maintenance of the atmospheric boundary layer (ABL) plays a
      key role in the distribution of atmospheric constituents, especially in a
      polluted urban area. In particular, the ABL has a direct impact on the
      concentration and transformation of pollutants. In this work, in order to analyze
      the different mechanisms which control the boundary layer growth, we have
      simulated by means of the non-hydrostatic model MM5 several boundary layer
      observed in the city of Barcelona (Spain). Sensitivity analysis of the modelled
      ABL is carried out by using various descriptions of the planetary boundary layer
      (PBL). Direct and continuous measurements of the boundary layer depth taken by a
      lidar are used to evaluate the results obtained by the model.

PMID- 15504508
TI  - The impact of highway emissions on ozone and nitrogen oxide levels during
      specific meteorological conditions.
AB  - The impact of highway emissions on O(3) and NO(x) was assessed using a validated
      air-quality model (MCCM-Multiscale Climate Chemistry Model) applied to a region
      of Southern Germany. During a measuring campaign around the City of Augsburg
      (Southern Germany) in May 2001 modelling calculations were performed, including a
      scenario in which the highway emissions (ca. 80,000 vehicles/day) between Munich
      and Augsburg (distance ca. 40 km) were switched off. Based on the change in
      emissions, the variations in O(3)- and NO(x)-concentrations as well as the size
      of the influenced area within the region of interest are discussed. Additionally,
      an episode in August 2001 with elevated ozone values was modelled for comparison
      with the May episode. The model results show a very pronounced reduction of O(3)-
      and an increase of NO(2)-concentrations after passing the highway within a
      distance of more than 40 km. After turning off the highway emissions it could be
      demonstrated that the emission reduction causes a significant increase in the
      ozone levels downwind of the highway in the magnitude of 10-20 ppbv depending on
      the time of the day.

PMID- 15504509
TI  - Short-range evaluation of air pollution near bus and railway stations.
AB  - In the early morning, during workdays, intensive activity is observed at both bus
      and railway stations. This particular time is critical because of the combination
      of three factors: (1) simultaneous departure of many buses and trains, (2) cold
      engines, and, quite frequently, (3) stable meteorological conditions. In our
      approach, we use ARIA Local, a simulation package applying CFD tools to air
      pollution modeling, to study different scenarios. The CFD model used in this
      study is the MERCURE model, developed by Electricite de France. For a bus
      station, we simulate a typical morning peak hour situation and study in detail
      how the pollution is accumulated in the station courtyard and the impact on the
      close vicinity. Two scenarios are presented: one with classical diesel engine and
      one with buses using AQUAZOL or NGV fuel. The definition of the sources inside
      the Eulerian grid is described as static linear sources. The total emission is
      averaged over the mean path driven by the bus from the bus stop to the exit of
      the bus station. For a railway station, we simulate a situation in a real railway
      station within the city of Paris. The emission from a diesel "locomotive" and its
      impact on air quality is computed and compared to the impact of other nonmobile
      emissions. In this case, the definition of sources is described as mobile point
      sources following the trajectory of the train. These two scenarios are discussed
      in an urban context, taking into account the flow around buildings and different
      meteorological conditions.

PMID- 15504510
TI  - Prioritising and planning of urban stormwater treatment in the Alna watercourse
      in Oslo.
AB  - The Oslo municipal Water and Sewage Works (VAV) intends to improve the water
      quality in the Alna watercourse, in particular, with regards to the biological
      diversity. In order to reduce existing discharges of polluted urban stormwater, a
      study has been carried out to rank subcatchment areas in descending order of
      magnitude and to assess possible measures. An overall ranking methodology was
      developed in order to identify and select the most suitable subcatchment areas
      for further assessment studies (74 subcatchment/drainage areas). The
      municipality's comprehensive geographical information system (GIS) was applied as
      a base for the ranking. A weighted ranking based on three selected parameters was
      chosen from several major influencing factors, namely total yearly discharge (kg
      pollution/year), specific pollution discharge (kg/area/year) and existing
      stormwater system (pipe lengths/area). Results show that the highest 15 ranked
      catchment areas accounted for 70% of the total calculated pollution load of heavy
      metals. The highest ranked areas are strongly influenced by three major highways.
      Based on the results from similar field studies, it would be possible to remove
      75-85% of total solids and about 50-80% of heavy metals using wet detention ponds
      as Best Available Technology (BAT). Based on the final ranking, two subcatchment
      areas were selected for further practical assessment of possible measures. VAV
      plans to use wet detention ponds, in combination with other measures when
      relevant, to treat the urban runoff. Using calculated loading and aerial
      photographs (all done in the same GIS environment), a preliminary sketch design
      and location of ponds were performed. The resulting GIS methodology for urban
      stormwater management will be used as input to a holistic and long-term planning
      process for the management of the watercourse, taking into account future urban
      development and other pollution sources.

PMID- 15504511
TI  - Sustainable stormwater management at Fornebu--from an airport to an industrial
      and residential area of the city of Oslo, Norway.
AB  - The Oslo Airport at Fornebu was closed in 1998 after 60 years of operation. An
      area of 3.1 km(2) was made available for one of Norway's biggest property
      development projects. Plans include 6000 residences and 20,000 workplaces.
      Fornebu is situated on a peninsula in the Oslo Fjord just outside the city of
      Oslo and is regarded as a very attractive area for both urbanisation and
      recreation. The residential area located centrally at Fornebu surrounds a
      centrally located park area. In the planning process, there was an expressed
      interest in using water as a life-giving element within the vegetation structure
      of the park. In Norway, stormwater in urban areas has traditionally been
      collected and transported in pipe systems to adjacent watercourses. However,
      there is an increasing interest in alternative "green" solutions for the
      management of stormwater. The paper presents a concept for sustainable stormwater
      management at Fornebu. A main objective is to improve the recreational and
      ecological value of stormwater while achieving a cost-effective solution. This
      objective is reached by replacing conventional urban drainage pipes with swales,
      filter strips, wetlands and ponds as collection, storage and treatment systems
      designed for natural processes. The paper thereby addresses integrated systems
      for stormwater management by approaching nature's way and sustainable development
      principles.

PMID- 15504512
TI  - Multicriteria decision approaches to support sustainable drainage options for the
      treatment of highway and urban runoff.
AB  - The control and treatment of urban and highway runoff involves a variety of
      stakeholders in the selection of sustainable drainage systems (SUDS) as the
      design process needs to consider not only water quantity but also water quality
      and amenity. Thus, technical, environmental/ecological, social/community and
      economic cost factors become prime potential sustainability criteria in terms of
      assessing long-term, cost-effective drainage options. The paper develops a
      multicriteria analysis methodology for the evaluation and accreditation of SUDS
      structures within the context of an overall decision-support framework.
      Approaches independently developed in the UK and France are outlined with the
      common multicriteria structures defining generic performance criteria together
      with supporting benchmark standards and exclusion thresholds. A French case study
      is presented to illustrate the approach and to highlight the inherent constraints
      and subjectivity embedded in the decision-making process.

PMID- 15504513
TI  - The performances of vegetative treatment systems for highway runoff during dry
      and wet conditions.
AB  - The performances of two different highway runoff treatment systems, a horizontal
      subsurface flow-constructed wetland and a vegetated balancing pond, are
      described. Both systems have been assessed by collecting inlet and outlet grab
      samples during wet and dry weather conditions, and automatically controlled storm
      event samples have been obtained for the constructed wetland. Removal
      efficiencies are discussed for BOD (grab samples only), suspended solids, Cd, Cr,
      Cu, Ni, Pb, Zn, nitrate and sulphate, and explanations are offered for the trends
      observed under different weather conditions. The large variabilities in the
      removal efficiencies derived for both treatment systems, based on the analyses of
      grab samples, make accurate comparisons of the performances difficult and also
      raise concerns about using this type of sampling approach for this purpose.
      Treatment systems are required to function satisfactorily during the increased
      inlet loadings experienced during storm events, and this is shown to be the case
      for the constructed wetland for the majority of the monitored pollutants. The
      large removal efficiency ranges for five separate storm events, exhibited by Cu
      and Pb, are discussed and compared to the other monitored pollutants which showed
      positive median wet weather removal efficiencies of between 43% and 85%. Despite
      the existence of performance fluctuations, the generally low monitored inlet
      concentrations in the highway runoff indicated that the pond discharges did not
      threaten the environmental quality of the receiving waters.

PMID- 15504514
TI  - Mobility of heavy metals within freshwater sediments affected by motorway
      stormwater.
AB  - The assessment of the mobility and bioavailability of heavy metals in sediment
      samples requires the use of sequential extraction procedures. Results for
      sediments taken from an unmanaged motorway detention pond showed heavy metals to
      be associated with the carbonate and residual fractions. In particular, nickel
      and cadmium showed a high percentage association, compared with other geochemical
      fractions, such as carbonates and residual fractions. Copper and zinc were shown
      to be associated with carbonates and iron-manganese oxides, whereas lead showed
      the strongest association (72%) with the Fe-Mn oxides. When compared to a
      groundwater-fed lake on the same site, all heavy metals contained within this
      sediment were found to be at much lower concentrations and strongly associated
      with the residual fraction (>50%) and are therefore strongly bound within the
      sediment. Following discharge via a wet detention pond, stormwater then flows
      through a series of interconnecting lake systems. Heavy metal fractionation of
      these interconnecting lakes is discussed and shows changes in fractionation
      through the lake system for copper, nickel, lead and zinc. The main concern in
      these lakes is the continued use of calcium carbonate to maintain freshwater pH
      for coarse fishing. This practice, used until 1999, may present an enhanced risk
      to the freshwater environment, causing greater mobility of these metals.

PMID- 15504515
TI  - Temporal trends of PCDDs/PCDFs in ambient air in Catalonia (Spain).
AB  - This paper reports the results of an assessment of dioxin levels in ambient air
      in samples collected in the four provinces of Catalonia (Spain) performed by the
      Environment Department of the Autonomous Government of Catalonia and the Spanish
      Council for Scientific Research (CSIC). The study includes compiled data of more
      than 133 samples collected in 28 different sites (rural, urban, suburban and
      industrial) between 1994 and 2002. The levels revealed a variable content of
      polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans (PCDDs/PCDFs)
      depending both on the area and the contamination source. Thus, concentrations
      from 16 to 954 fg I-TEQ/Nm(3), with a mean value of 180 fg I-TEQ/Nm(3), were
      determined in industrial areas. The levels found in urban and suburban sites
      varied from 10 to 357 fg I-TEQ/Nm(3), with a mean value of 80 fg I-TEQ/Nm(3). The
      lowest concentrations were found in rural areas, ranging from 5 to 125 fg I
      TEQ/Nm(3), with a mean value of 42 fg I-TEQ/Nm(3). As part of the project, levels
      of samples collected in parallel using two different samplers, a total suspended
      particulate (TSP) sampler and PM10 sampler, were compared. The results of 11
      different campaigns indicated that both methods are comparable and no significant
      differences were determined.

PMID- 15504516
TI  - An uncertainty analysis of air pollution externalities from road transport in
      Belgium in 2010.
AB  - Although stricter standards for vehicles will reduce emissions to air
      significantly by 2010, a number of problems will remain, especially related to
      particulate concentrations in cities, ground-level ozone, and CO(2). To evaluate
      the impacts of new policy measures, tools need to be available that assess the
      potential benefits of these measures in terms of the vehicle fleet, fuel choice,
      modal choice, kilometers driven, emissions, and the impacts on public health and
      related external costs. The ExternE accounting framework offers the most up to
      date and comprehensive methodology to assess marginal external costs of energy
      related pollutants. It combines emission models, air dispersion models at local
      and regional scales with dose-response functions and valuation rules. Vito has
      extended this accounting framework with data and models related to the future
      composition of the vehicle fleet and transportation demand to evaluate the impact
      of new policy proposals on air quality and aggregated (total) external costs by
      2010. Special attention was given to uncertainty analysis. The uncertainty for
      more than 100 different parameters was combined in Monte Carlo simulations to
      assess the range of possible outcomes and the main drivers of these results.
      Although the impacts from emission standards and total fleet mileage look
      dominant at first, a number of other factors were found to be important as well.
      This includes the number of diesel vehicles, inspection and maintenance (high
      emitter cars), use of air conditioning, and heavy duty transit traffic.

PMID- 15504517
TI  - New Zealand traffic and local air quality.
AB  - Since 1996 the New Zealand Ministry of Transport (MOT) has been investigating the
      effects of road transport on local air quality. The outcome has been the
      government's Vehicle Fleet Emissions Control Strategy (VFECS). This is a
      programme of measures designed to assist with the improvement in local air
      quality, and especially in the appropriate management of transport sector
      emissions. Key to the VFECS has been the development of tools to assess and
      predict the contribution of vehicle emissions to local air pollution, in a given
      urban situation. Determining how vehicles behave as an emissions source, and more
      importantly, how the combined traffic flows contribute to the total emissions
      within a given airshed location was an important element of the programme. The
      actual emissions output of a vehicle is more than that determined by a certified
      emission standard, at the point of manufacture. It is the engine technology's
      general performance capability, in conjunction with the local driving conditions,
      that determines its actual emissions output. As vehicles are a mobile emissions
      source, to understand the effect of vehicle technology, it is necessary to work
      with the average fleet performance, or "fleet-weighted average emissions rate".
      This is the unit measure of performance of the general traffic flow that could be
      passing through a given road corridor or network, as an average, over time. The
      flow composition can be representative of the national fleet population, but also
      may feature particular vehicle types in a given locality, thereby have a
      different emissions 'signature'. A summary of the range of work that has been
      completed as part of the VFECS programme is provided. The NZ Vehicle Fleet
      Emissions Model and the derived data set available in the NZ Traffic Emission
      Rates provide a significant step forward in the consistent analysis of practical,
      sustainable vehicle emissions policy and air-quality management in New Zealand.

PMID- 15504518
TI  - What lies beneath?--issues in the representation of air quality management data
      for public consumption.
AB  - Policy developments in the UK and the European Union (EU) now require local
      authorities to engage the general public within the whole process of local air
      quality management (AQM). Indeed, this is considered to be one of the means by
      which air quality issues can gain public support and help ensure future
      improvements. One of the outcomes of this is that data sets associated with air
      quality management must now be disseminated to nonscientific audiences. This is a
      problematic task for a number of reasons. One of these relates to the fact that
      air quality data are complex and variable, yet the public demand representations
      that are clear and unambiguous. Another important issue is associated with the
      increasing use of geographical information systems (GIS) and mapping tools, which
      allow data to be generated and summarised in many different ways without due
      regard to the effects that the choice of methodology can have on the way data are
      interpreted. The variation in information obtained using different techniques can
      represent a problem, but is also an opportunity to further explore data sets and
      to draw out specific information for complementary air quality management tasks.
      However, at present, the lack of a well-grounded methodology and guidance for
      handling and representing the spatial aspects of data sets means that consistency
      between areas and authorities is not maintained. Such a situation fosters
      ambiguity at several levels, from the individual's perception of public health
      related information to an Authority's rationale for the selection of air quality
      management areas (AQMAs). This paper investigates a number of issues relating to
      spatial data generation and representation in the field of air quality
      management, particularly in relation to emissions inventory data. The examples
      are UK based, but the issues raised are applicable to other examples and areas.
      One case study examines the difference in information gained through a number of
      common mapping techniques and shows how different 'problems' can be identified
      merely as an artefact of the dissemination technique itself. To further
      illustrate the difficulties and conflicts faced in representing and explaining
      these data in a practical context, reference is then also made to the methods
      recently considered by an example London authority. The paper concludes with a
      call for the development of a more standardised method for representing different
      types of air quality management-related data, which may help to overcome these
      problems in the future.

PMID- 15504519
TI  - Street canyon aerosol pollutant transport measurements.
AB  - Current understanding of dispersion in street canyons is largely derived from
      relatively simple dispersion models. Such models are increasingly used in
      planning and regulation capacities but are based upon a limited understanding of
      the transport of substances within a real canyon. In recent years, some efforts
      have been made to numerically model localised flow in idealised canyons (e.g., J.
      Appl. Meteorol. 38 (1999) 1576-89) and stepped canyons (Assimakopoulos V.
      Numerical modelling of dispersion of atmospheric pollution in and above urban
      canopies. PhD thesis, Imperial College, London, 2001) but field studies in real
      canyons are rare. To further such an understanding, a measurement campaign has
      been conducted in an asymmetric street canyon with busy one-way traffic in
      central Manchester in northern England. The eddy correlation method was used to
      determine fluxes of size-segregated accumulation mode aerosol. Measurements of
      aerosol at a static location were made concurrently with measurements on a
      platform lift giving vertical profiles. Size-segregated measurements of ultrafine
      and coarse particle concentrations were also made simultaneously at various
      heights. In addition, a small mobile system was used to make measurements of
      turbulence at various pavement locations within the canyon. From this data,
      various features of turbulent transport and dispersion in the canyon will be
      presented. The concentration and the ventilation fluxes of vehicle-related
      aerosol pollutants from the canyon will be related to controlling factors. The
      results will also be compared with citywide ventilation data from a separate
      measurement campaign conducted above the urban canopy.

PMID- 15504520
TI  - Characterisation of aerosol particulate matter from urban and industrial
      environments: examples from Cardiff and Port Talbot, South Wales, UK.
AB  - A high-volume cascade impact collector (1100 l/min air flow) was used to collect
      air samples in an industrial (Port Talbot) and an urban (Cardiff) site with the
      purpose of characterising both coarse (PM(10-2.5)) and fine (PM(2.5)) fractions
      comprising the total sample. PM(10-2.5) and PM(2.5) samples were collected by
      cascading air through two polyurethane foams on which particles impact and become
      deposited. Air sample collection rates are to some extent dependent on weather
      conditions, notably rainfall, humidity, and especially, wind direction, but
      samples show a very different and distinctive air particle composition between
      the two collection sites. Thus, although both Cardiff and Port Talbot are coastal
      sites and therefore have high contents in chlorides, Port Talbot is extremely
      rich in tiny Fe spherules (>30%, in both coarse and fine fractions) from a nearby
      steel plant. Mineralogical characterisation using SEM-EDX shows a clear
      fractionation between the particle composition in the PM fractions, with the
      coarse fraction being dominated by chlorides, sulphates (gypsum), and silicates,
      and the fine fraction having high proportions of ammonium sulphates and elemental
      and organic carbon compounds, most of the latter being linked to traffic
      pollution.

PMID- 15504521
TI  - Identifying the contribution of different urban highway air pollution sources.
AB  - This paper describes the methodology and results, and draws conclusions from a
      large-scale source apportionment study undertaken in a large urban conurbation in
      the northwest of England. Annual average oxides of nitrogen (NOx) emission and
      ambient air pollution contributions have been estimated for road traffic sources.
      Ground level air pollution concentrations were estimated over a 1552-km(2) area
      with a resolution of up to 20 m, using emissions estimates and the second
      generation ADMS-Urban Gaussian dispersion model. Road traffic emissions were
      split into car and motorcycles; heavy and light goods vehicles; and buses to
      represent domestic users; commercial users and bus companies. Car related
      emissions were split further in to journey lengths under 3 km; journeys between 3
      and 8 km; and journeys over 8 km to represent journeys which could be either
      walked or cycled; journeys for which a bus can easily be used and other journeys.
      These source sections were chosen so that the relevant authorities could target
      key groups in terms of reducing air pollution. The results confirm that the areas
      most likely to exceed air quality objectives are typically close to main arterial
      routes and close to urban centres and that the major culprits of road traffic
      related air pollution are goods vehicles and car journeys over 8 km. The paper
      also discusses the implications of the results and suggests how these can be used
      in the assessment of actions to reduce air pollution concentrations.

PMID- 15504522
TI  - Levels of particulate matter in rural, urban and industrial sites in Spain.
AB  - This paper summarises the results of a series of studies on the interpretation of
      time series of levels of total suspended particles (TSP) and particulate matter
      (PM, <10 microm) in six regions of Spain in the period 1996-2000. In addition to
      the local pollution events, high PM10 episodes are recorded during African dust
      outbreaks, regional atmospheric recirculation events (mainly in spring to
      autumn), and to a lesser extent, under the influence of European and
      Mediterranean long range transported air masses. The lowest PM10 levels are
      usually recorded under Atlantic air mass advective conditions. All these regional
      and large-scale processes account for the relatively high PM10 levels recorded in
      regional background stations in Spain. Thus, the PM10 levels recorded at EMEP
      (Cooperative Program for Monitoring and Evaluation of the Long Range Transmission
      of Air Pollutants in Europe) regional background stations between March 2001 and
      March 2002 are very close to the annual limit value proposed for 2010 by the EU
      Air Quality Directive 1999/30/CE. Chemical data obtained for the different
      monitoring stations during 2001 show a high mineral load in PM10 for most of the
      study sites in Spain. Furthermore, a high marine aerosol load is evidenced in the
      Canary Islands. These mineral and marine loads are lower when considering PM2.5,
      but a relatively high proportion (8-21%) of mineral dust is still present.

PMID- 15504523
TI  - Assessment of methodologies for airborne BaP analysis.
AB  - Very sensitive analytical methods will be required to assess airborne
      contaminants with the implementation of new EC Directives. In this work, Soxhlet,
      ultrasonic and microwave-assisted extraction (MAE) were applied to two airborne
      standard reference materials (SRM) 1648 "Urban Particulate Matter" and SRM 1649a
      "Urban Dust". All three techniques afforded satisfactory results, but MAE was
      preferred due to its low solvent requirement and speed of analysis. In addition,
      high performance liquid chromatography (HPLC) with ultraviolet and fluorescence
      detection was compared to gas chromatography (GC)-flame ionisation detection
      (FID) with programmed split-splitless injection (PSS) and GC-mass spectrometry
      (MS) with programmed temperature vaporiser (PTV) injection. The HPLC method
      proved far more sensitive than the GC techniques (four and three orders of
      magnitude, respectively). Real atmospheric particulate samples were taken at A
      Coruna (Spain). Different sampling devices were used to collect PM(10), PM(2.5),
      PM(1), cascade impactor and TSP/gas phase samples. BaP concentrations quantified
      in the samples are similar to those reported for other cities.

PMID- 15504524
TI  - Comparison of road traffic emission factors and testing by comparison of modelled
      and measured ambient air quality data.
AB  - This paper describes a comparison of three different sets of road traffic
      emission factors released by the UK government for use in air quality review and
      assessment. The air quality management process of review and assessment began in
      1997 in the UK. During this period of ongoing review and assessment, a number of
      changes have been made to the emission factors provided by the government. The
      use of different sets of emission factors during the assessment process has lead
      to some inconsistencies between results from neighbouring local authorities and
      also between different modelling exercises undertaken by the same local
      authorities. One purpose of this study has been to compare three different sets
      of emission factors, including the most recent set, and to some degree highlight
      the uncertainty associated with the use of factors, such as the shift of emphasis
      in terms of emissions from cars to heavy goods vehicles. The most recently
      released emission factors are the most comprehensive to date, and theoretically
      more accurate than previous sets due to the larger database of emission
      measurements that they have been based on. Therefore, the most recent set of
      emission factors have been additionally used in a validation exercise between
      modelled and monitored data. Comparison has been undertaken with monitoring data
      at a variety of urban background, urban centre and roadside sites. This work has
      shown some differences between the predicted trends in emission factors and
      measured trends in ambient air pollution levels, especially at roadside sites,
      indicating an under-prediction of the air pollution contribution from road
      traffic.

PMID- 15504525
TI  - Health and environmental testing of manganese exhaust products from use of
      methylcyclopentadienyl manganese tricarbonyl in gasoline.
AB  - This paper reviews recent research on the environmental effects of
      methylcyclopentadienyl manganese tricarbonyl (MMT), personal exposures to
      airborne Mn as a result of MMT use, chemical characterization of the manganese
      particulates emitted from the tailpipe and progress in developing a (PBPK) model
      for manganese in rodents. Recent studies show that manganese is emitted as a
      mixture of compounds with an average valence of about 2.2. The major products are
      sulfate, phosphate, and smaller amounts of oxides. Because only small amounts of
      Mn are used in gasoline (<18 mg Mn/gal) and less than 15% of the combusted Mn is
      emitted, soil along busy roads is not elevated in Mn, even after long-term use of
      MMT. A very large population-based study of manganese exposures in the general
      population in Toronto, where MMT has been used continuously for over 20 years,
      showed that manganese exposures were quite low, the median annual exposure was
      0.008 microg Mn/m(3). A great amount of toxicological research on Mn has been
      carried out during the past few years that provides data for use in developing a
      PBPK model in rodents. These data add greatly to the existing body of knowledge
      regarding the relationship between Mn exposure and tissue disposition. When
      complete, the PBPK model will contribute to our better understanding of the
      essential neurotoxic dynamics of Mn.

PMID- 15504526
TI  - Manganese exposure and induced oxidative stress in the rat brain.
AB  - Neurotoxicity linked to excessive brain manganese levels can occur as a result of
      high level Mn exposures and/or metabolic aberrations (liver disease and decreased
      biliary excretion). Increased brain manganese levels have been reported to induce
      oxidative stress, as well as alterations in neurotransmitter metabolism with
      concurrent neurobehavioral and motor deficits. Two putative mechanisms in which
      manganese can produce oxidative stress in the brain are: (1) via its oxidation of
      dopamine, and (2) interference with normal mitochondrial respiration.
      Measurements of antioxidant species (e.g., glutathione and metallothionein), and
      the abundance of proteins (enzymes) exquisitely sensitive to oxidation (e.g.,
      glutamine synthetase) have been commonly used as biomarkers of oxidative stress,
      particularly in rat brain tissue. This paper examines the link between manganese
      neurotoxicity in the rat brain and common pathways to oxidative stress.

PMID- 15504527
TI  - The use of a European telemedicine system to examine the effects of pollutants
      and allergens on asthmatic respiratory health.
AB  - The experience of using a telemedicine feasibility study to integrate respiratory
      health response and environmental stimuli information is presented. The effects
      of ambient air quality, pollen and local environment conditions on asthmatic
      patients' lung function were investigated through the use of a novel European
      health telematic system. The Medical Diagnosis, Communication and Analysis
      Throughout Europe (MEDICATE) project developed and tested the feasibility of
      using a telemedicine system for chronic asthmatics in London, UK, and Barcelona,
      Spain. The key to this was the determination of the real time health (lung
      function) response to the ambient environment and allergens. Air quality, pollen
      and environmental lifestyle information were related to respiratory measurements
      for recruited asthmatic patients in the study through the design of a dedicated
      environmental management system (EMS) database. In total, 28 patients completed
      the study trial, subject to ambulatory monitoring of spirometric lung function
      (PEF, FEV(1) and FVC) up to four times a day over a 2-week period recorded during
      the year 2000. Alongside this, ambient air quality and pollen counts were used to
      represent local exposure to potential environmental stimuli. Personal
      questionnaire interviewing collected additional data about patient lifestyles,
      social-economic conditions and quality of life perceptions. The methods and
      indicative results of integrating environmental and health data in this respect
      are examined. Assessment tools such as GIS and object-orientated databases were
      designed to locate and compile environmental information about the patients'
      locations and lifestyles in the study areas (London and Barcelona). Socioeconomic
      and lifestyle factors, such as exposure to smoking, pets, personal journey
      lengths and modes, income, household occupancy and domestic fuel use, were found
      to have limited detectable effects on the patients' basic lung function levels.
      Patients' gender, age and predicted PEFR were significantly associated with the 2
      week mean and minimum respiratory measurements. Lung function data were compared
      with air quality and pollen indicators to examine relationships on a daily or
      lagged-day basis controlling for confounding factors. The paper discusses the new
      methodology and the practicalities of using the telemedical system as a tool for
      assessing the impacts of environmental stimuli on respiratory health.

PMID- 15504528
TI  - Valuation of social and health effects of transport-related air pollution in
      Madrid (Spain).
AB  - Social impacts of pollutants from mobile sources are a key element in urban
      design and traffic planning. One of the most relevant impacts is health effects
      associated with high pollution periods. Madrid is a city that suffers chronic
      congestion levels and some periods of very stable atmospheric conditions; as a
      result, pollution levels exceed air quality standards for certain pollutants.
      This paper focuses on the social evaluation of transport-related emissions. A new
      methodology to evaluate those impacts in monetary terms has been designed and
      applied to Madrid. The method takes into account costs associated with losses in
      working time, mortality and human suffering; calculated using an impact pathway
      approach linked to CORINAIR emissions. This also allows the calculation of social
      costs associated with greenhouse gas impacts. As costs have been calculated
      individually by effect and mode of transport, they can be used to design pricing
      policies based on real social costs. This paper concludes that the health and
      social costs of transport-related air pollution in Madrid is 357 Meuro. In these
      circumstances, the recent public health tax applied in Madrid is clearly correct
      and sensible with a fair pricing policy on car use.

PMID- 15504529
TI  - Killer smog of London, 50 years on: particle properties and oxidative capacity.
AB  - Total suspended particulate (TSP) samples collected on glass fibre filters in
      London before (1955) and after (1958-1974) the Clean Air Act was examined for
      physicochemical characteristics and oxidative capacity. High-resolution
      microscopy identified most of the material as soot with smelter spheres, fly ash
      (FA), sodium chloride and calcium sulphate particles. Image analysis (IA) was
      used to show that most of the soot aggregates were less than 1 microm in size and
      contained chains of individual particles of 10-50 nm. Speed mapping of large
      agglomerates of the historic particles confirmed that the samples were enriched
      with soot probably derived from a sulphur-rich coal called nutty slack which was
      used extensively at this time. Inductively coupled plasma-mass spectrometry (ICP
      MS) was used to examine elemental composition. Meaningful quantitation of certain
      elements (Mg, Al and Zn) proved impossible because they were in high quantities
      in the glass fibre filters. However, high quantities of Fe>Pb>Cu>Mn>V>As were
      detected which may explain in part the bioreactivity of the samples. Using a
      simple in vitro test of oxidative capacity (plasmid assay), one historic
      particulate sample (1958) showed three times the activity of a modern-day diesel
      exhaust particle (DEP) sample but ten times less activity than a modern-day urban
      ambient particle collection. Such studies are continuing to link particle
      physicochemical properties and bioreactivity with a wider range of the samples
      collected between 1955 and 74 and how such historic samples compare with present
      day London ambient particles.

PMID- 15504530
TI  - Platinum levels in nasal lavage fluid as a biomarker for traffic-related exposure
      and inflammation in children.
AB  - Platinum (Pt) is a well-known constituent of particles emitted by catalytic
      converters during car operation. To evaluate Pt as a potential marker for traffic
      related particle exposure, we investigated Pt content along with metals vanadium
      (V) and chromium (Cr) in coarse and fine particulate matter (PM), sampled in four
      areas with different traffic density, as well as in the nasal lavage (NAL) of 67
      children (average age: 6 years) living in these areas. The different sites were
      characterised by significant differences in air pollutants including PM, NO,
      NO(2), CO and Cr, but differences in V or Pt were absent. No significant
      differences in neutrophil and epithelial cell counts or concentrations of the
      neutrophil chemoattractant interleukin-8 (IL-8) were found in the NAL of children
      living in the different areas. In addition, the concentrations of V, Cr and Pt,
      which were detectable in 64%, 73% and 93% of the individuals, respectively, did
      not differ between the different locations. However, in the NAL of the children,
      a significant correlation between Pt and the number of neutrophils/ml (r=0.40,
      p<0.001) as well as of epithelial cells/ml (r=0.41, p<0.001) was found. No
      relation was present between nasal inflammation and nasal Cr levels, whereas a
      relatively weak association was observed between V and epithelial cells counts
      (r=0.30, p=0.018). In conclusion, our data suggests a role for nasal lavage Pt as
      a candidate biomarker for traffic-related PM, which is able to induce
      inflammation in the upper respiratory tract.

PMID- 15504531
TI  - Platinum emissions and levels in motorway dust samples: influence of traffic
      characteristics.
AB  - An increase in the environmental levels of platinum can in part be attributed to
      the introduction of motor vehicle catalytic converters. Reported platinum levels
      in roadside dust samples range from 0.6 ng/g to 62.8+/-10.5 microg/g (dry weight,
      d.w.), with the highest levels in samples taken from inside road tunnels.
      Carriageway dust samples were collected from nine junctions (at sites of rush
      hour 'stop-start' activity or slip road on/off sections) of the London Orbital
      (M25) motorway and analysed for total Pt by inductively coupled plasma mass
      spectrometry (ICP-MS). These motorway junctions have mean daily traffic densities
      of 85,000 to 145,000 vehicles. Dust samples were fractionated (<75, 75-125 and
      125-250 microm), microwave acid digested (aqua rega/HF) and analysed using
      (195)Pt(+) with polyatomic ion correction of (179)Hf(16)O(+). Quality control
      validation was performed with replicate analysis of two certified reference
      materials, namely, NIST 2556 (Used Autocatalyst-Pellet) and 2557 (Used
      Autocatalyst-Monolith). Total platinum levels (sum total of all particle
      fractions) ranged from 101.6 to 764.2 ng/g (dry weight) in dust samples from all
      sampling sites. The highest Pt levels occur in the <75 and 75-125 microm particle
      fractions, with the fractionated samples ranging from 4.6 to 356.2 ng/g Pt (dry
      weight). Statistical analysis (Student t-test) confirmed that the significantly
      higher Pt levels (at the 95% confidence interval) occurred in dust samples taken
      from carriageway sites that had the vehicle slowing/stop-start driving conditions
      rather than for the accelerating speed zones. Correlation analysis showed that
      dust Pt levels, irrespective of fraction particle size, did not directly relate
      to traffic density, which is contrary to other published studies. The highest Pt
      levels occurred at the M25/A3 (Portsmouth/Guildford to London highway)
      intersection suggesting that traffic flow conditions, such as erratic stop-start
      flows, have a greater influence on Pt particle release and accumulation in the
      adjacent motorway environment than traffic density.

PMID- 15504532
TI  - Integrated assessment of traffic impact in an Alpine region.
AB  - This paper reports the results of an integrated assessment of traffic impact on a
      tourist-popular high altitude region which includes mountain passes and road
      tunnels. A modeling system for air quality assessment and management has been
      established and revised. The system has been used to evaluate the impact of
      traffic due to the re-opening of the Mont Blanc tunnel: the increase in NO(x)
      concentrations ranges from 50% at the bottom of the upper valley to 150% near to
      tunnel entrance.

PMID- 15504533
TI  - Sediment accumulation in newly constructed vegetative treatment facilities along
      a new major road.
AB  - The A34 Newbury bypass was opened in England in November 1998. This 15 km of
      roadway has nine constructed vegetative treatment systems incorporating oil
      separators, silt traps, grass filters for primary filtration and chemical
      absorption, reed wetlands for secondary biofiltration, a deep water pool and
      outflow device to control the rate of water discharge into existing watercourses.
      Two of these facilities discharge stormwater into the Lambourn sites of special
      scientific interest (SSSI) river. An evaluation of the heavy metal levels in
      these two ponds (Ponds J and K) has been undertaken in the 39-month period after
      the opening of the bypass. Motorway-derived contaminants including Pb, Cd, Cu and
      Zn were evaluated within pond sediment throughout these treatment facilities.
      Results reveal that heavy metal levels within the treatment system that possesses
      a well-established reed bed system decrease rapidly though the facility. It is
      postulated that the high reed biomass within this facility may be primarily
      responsible for reducing hydraulic flow thus allowing a greater residence time
      for sedimentation, filtration and bioaccumulation processes.

PMID- 15504534
TI  - Sustainable development of urban transport systems and human exposure to air
      pollution.
AB  - DAPPLE (Dispersion of Air Pollution and Penetration into the Local Environment,
      http://www.dapple.org.uk) is a major research project that will provide the
      understanding necessary to assess the sustainability of urban road transport in
      terms of exposure to traffic-related air pollution as an alternative to current
      indicators based on emissions, roadside, or far-from-road air pollution levels.
      The methodology is described, which combines on-street and laboratory measurement
      with modelling of the movement of air, vehicles, and vehicle exhaust emissions.
      The relationship between this kind of assessment and more realistic indicators of
      sustainability is discussed. The value of large-scale interdisciplinary research
      in this area is thus demonstrated.

PMID- 15504535
TI  - An integrated methodology to assess the benefits of urban green space.
AB  - The interrelated issues of urban sprawl, traffic congestion, noise, and air
      pollution are major socioeconomic problems faced by most European cities. A
      methodology is currently being developed for evaluating the role of green space
      and urban form in alleviating the adverse effects of urbanisation, mainly
      focusing on the environment but also accounting for socioeconomic aspects. The
      objectives and structure of the methodology are briefly outlined and illustrated
      with preliminary results obtained from case studies performed on several European
      cities.

PMID- 15504536
TI  - Canine Leishmaniasis.

PMID- 15504537
TI  - Canine leishmaniasis.
AB  - Canine leishmaniasis is caused by Leishmania infantum (syn. L. chagasi, in
      America) and is transmitted by the bite of phlebotomine sand flies. Infected dogs
      constitute the main domestic reservoir of the parasite and play a key role in
      transmission to humans, in which the parasite produces visceral leishmaniasis.
      The increasing awareness that control of the human disease depends on effective
      control of canine leishmaniasis has promoted, in the last few years, research
      into leishmanial infection in dogs. Newly available specific reagents and
      molecular tools have been applied to the detailed investigation of canine
      leishmaniasis and important advances have been made in elucidating the
      epidemiology and pathology of the disease. These new findings have led to better
      understanding of the disease, and have also helped in the development of new
      diagnostic methods and control measures against the infection, such as
      insecticide-impregnated collars for dogs, new drugs and treatment protocols, and
      second generation vaccines, with the hope of not only reducing the heavy burden
      of the disease among dogs but also reducing the incidence of human visceral
      leishmaniasis.

PMID- 15504538
TI  - Sexual biology of schistosomes.
AB  - Schistosomes are unusual, together with some of the didymozoidae, in that they
      are dioecious instead of being hermaphrodite. This gonochorism is accompanied
      with morphological, ecological, behavioural and molecular differences between the
      male and the female parasites all through their life cycle. This review is an
      overview of the sexual biology of schistosomes and aims to provide the most
      recent information that may help to build future control strategies against these
      parasites. It proposes a new view of the life cycle of schistosomes, taking into
      account the sexual status of each developmental stage. It presents the relevant
      information available on the genetic and phenotypic sexual dimorphisms of these
      parasites; it proposes a comparison between the host-male parasite and the host
      female parasite interactions in both the molluscan intermediate and the mammalian
      definitive hosts; it exposes the male-female parasite interactions that exist in
      both the mollusc and the mammalian hosts at the parasite individual and
      populational levels. This review highlights the domains of research that are
      still unexplored but that would be of great interest for a better knowledge of
      the sexual way of life of the parasites which are still responsible for one of
      the most important human parasitic diseases in the world.

PMID- 15504539
TI  - Review of the trematode genus Ribeiroia (Psilostomidae): ecology, life history
      and pathogenesis with special emphasis on the amphibian malformation problem.
AB  - Trematodes in the genus Ribeiroia have an indirect life cycle involving planorbid
      snails as first intermediate hosts, fishes or amphibians as second intermediate
      hosts and birds or mammals as definitive hosts. Although rarely pathogenic in
      definitive hosts, Ribeiroia infection can cause severe pathology and mortality in
      snails and amphibians. This group of parasites has gained notoriety for its
      prominent rol in the recent rash of amphibian deformities in North America. Under
      some circumstances, these malformations may enhance parasite transmission by
      rendering infected amphibian hosts more susceptible to definitive host predators.
      However, increasing reports of malformations in North American amphibian
      populations emphasize the importance of understanding infection patterns. Here we
      review important aspects of the biology, ecology, life cycle and pathogenesis of
      parasites in the genus Ribeiroia and identify priorities for future research.
      Based on available morphological descriptions and preliminary molecular data,
      three species of Ribeiroia are recognized: R. ondatrae in the Americas, R. marini
      in the Caribbean and R. congolensis/C. lileta in Africa. We further evaluate the
      influence of abiotic and biotic factors in determining the intensity and
      prevalence of Ribeiroia infection and malformations in amphibians, highlighting
      the importance of habitat alteration and secondary factors (e.g. aquatic
      eutrophication, contaminants) in promoting infection. Although not a "new"
      parasite, Ribeiroia may have increased in range, prevalence, or intensity in
      recent years, particularly within amphibian hosts. Nevertheless, while much is
      known about this intriguing group of parasites, there remains much that we do not
      know. Particular importance for future research is placed on the following areas:
      evaluating the phylogenetic position of the genus, establishing the molecular
      mechanism of parasite-induced malformations in amphibians, isolating the drivers
      of parasite transmission under field conditions and studying the consequences of
      malformations for parasite and host populations. Investigation of these questions
      will benefit enormously from a multidisciplinary approach that effectively
      integrates parasitology, developmental biology, immunology, herpetology and
      aquatic ecology.

PMID- 15504540
TI  - The Trichuris muris system: a paradigm of resistance and susceptibility to
      intestinal nematode infection.
AB  - Gastrointestinal helminths infect over 1 billion people worldwide. Although
      rarely causing death, such diseases are associated with high levels of morbidity
      and furthermore bear a large economic burden within areas where infections are
      endemic. Trichuris muris, a natural intestinal parasite of mice has been
      extensively utilised as a laboratory model for the study of human whipworm
      Trichuris trichiura. This has proven to be an invaluable tool in dissecting the
      different components involved in immunity to trichuris infection. Moreover, it
      has become a paradigm of cytokine mediated immunity to gastrointestinal nematodes
      in general. It is well established that resistance and susceptibility to T. muris
      infection are tightly associated with the generation of a T helper 2 (TH2) or a T
      helper 1 (TH1) immune response, respectively. This review gives a detailed
      account of the experimental work which has provided us with this knowledge, and
      further builds upon this, by focusing upon the most recent developments and
      important findings from this host-parasite relationship.

PMID- 15504541
TI  - Scabies: new future for a neglected disease.
AB  - Scabies is a disease of global proportions in both human and animal populations,
      resulting from infestation of the skin with the "itch" mite Sarcoptes scabiei.
      Despite the availability of effective chemotherapy the intensely itching lesions
      engender significant morbidity primarily due to secondary sepsis and post
      infective complications. Some patients experience an extreme form of the disease,
      crusted scabies, in which many hundreds of mites may infest the skin causin
      severe crusting and hyperkeratosis. Overcrowded living conditions and poverty
      have been identified as significant confounding factors in transmission of the
      mite in humans. Control is hindered by difficulties with diagnosis, the cost of
      treatment, evidence for emerging resistance and lack of effective vaccines.
      Historically research on scabies has been extremely limited because of the
      difficulty in obtaining sufficient quantities of the organism. Recent molecular
      approaches have enabled considerable advances in the study of population genetics
      and transmission dynamics of S. scabiei. However, the most exciting and promising
      development is the potential exploitation of newly available data from S. scabiei
      cDNA libraries and EST projects. Ultimately this knowledge may aid early
      identification of disease, novel forms of chemotherapy, vaccine development and
      new treatment possibilities for this important but neglected parasite.

PMID- 15504542
TI  - Summary of the 12th international symposium on recent advances in stem cell
      transplantation.

PMID- 15504543
TI  - The hemangioblast: cradle to clinic.
AB  - In the embryo, the mesodermal precursor cell, the hemangioblast, gives rise to
      blood and blood vessels. During adult life, the hematopoietic stem cell (HSC)
      also exhibits this bipotential hemangioblast activity, serving as a rich source
      for circulating endothelial progenitor cells (EPCs). As a result of this finding,
      many questions have arisen as to whether the adult HSC is involved in the day-to
      day maintenance of tissues, what mechanisms influence this adult hemangioblast
      activity, and whether blood vessels harbor hematopoietic capability. In answering
      these questions, the power of adult hemangioblast activity could be harnessed to
      evaluate and treat diseases such as myocardial infarction, stroke, cancer, and
      blindness. Enumeration of activated EPCs aims to alert the patient as to the
      severity of their disease, predict response to therapy, and gauge for relapse
      potential. Identification of hemangioblast stimulatory or inhibitory cues would
      allow physicians to regulate neovascularization in their patient, augmenting
      vessel production in situations of hypo-proliferation such as wound healing and
      inhibiting vessel production in situations of hyper-proliferation such as cancer.
      Finally, given that EPCs home to sites of new blood vessel growth, genetic
      engineering of harvested HSC or EPC offers the potential to deliver
      vasoregulatory factors directly to sites of neovascularization.

PMID- 15504544
TI  - Enrichment of rare cancer cells through depletion of normal cells using density
      and flow-through, immunomagnetic cell separation.
AB  - OBJECTIVE: To develop a reliable technique to enrich for rare cells in blood
      suspensions using only negative selection steps including a flow-through
      immunomagnetic cell separations system and by optimizing variables normally
      encountered during such enrichment processes. METHODS: A human breast cancer cell
      line was cultivated and spiked at a ratio of 1 cancer cell to 10(5) total
      leukocytes in buffy coat or 1 cancer cell to 10(8) total cells in whole blood
      samples. The final, optimized process consisted of: a red cell lysis step,
      immunomagnetically staining leukocytes with an anti-CD45 PE, anti- MACS sandwich,
      immunomagnetic sorting using a flow-through system (QMS), and a final cell
      analysis step using either an automated cell counter, filtration, and visual
      counting or a cytospin analysis. RESULTS: The final, optimized process produced a
      final enrichment of the rare cancer cells of 5.17 log(10) and an average, final
      recovery of 46%. It should be noted that a negative depletion protocol was used
      (i.e., no labeling of the rare cancer cells was used). CONCLUSIONS: To the
      authors' knowledge, no examples in the literature exist of a 5.17 log(10)
      enrichment of cancer cells in human blood using a negative depletion protocol.
      The closest example is a 4 log(10) enrichment in which two positive magnetic cell
      separation steps were used (none were used in this study). Ongoing studies are
      investigating further modifications of the precommercial, prototype flow-through
      immunmagnetic separation system to increase both the enrichment and recovery
      rate. However, even at current performance levels, the presented process could
      significantly improve visual and molecular analysis of rare cells in blood.

PMID- 15504545
TI  - Osteosclerosis in idiopathic myelofibrosis is related to the overproduction of
      osteoprotegerin (OPG).
AB  - OBJECTIVE: The aim of this study is to investigate the mechanism of
      osteosclerosis in IMF in relation to OPG derangement. METHODS: Plasma OPG level
      was assayed by OPG ELISA in 19 patients with IMF, 15 patients with other
      myeloproliferative disorders (MPDs), and 12 normal volunteers as controls and
      correlated with the degree of osteosclerosis. Furthermore, the level of OPG mRNA,
      in the cultured bone marrow stromal (BMS) cells of patients with IMF and anemia
      patients used as controls, in the presence or absence of TGF-beta1, was studied
      by real-time RT-PCR. RESULTS: The present study showed that blood OPG level was
      significantly elevated in patients with IMF as compared to patients with other
      MPDs (p < 0.01) or normal volunteer controls (p < 0.05), and there was no
      significant difference in the level between patients with MPDs and controls. In
      addition, there was a positive correlation (r=0.67, p=0.04) between plasma OPG
      levels and the degree of osteosclerosis. There was no difference in the OPG mRNA
      in patients with IMF as compared with controls even on TGF-beta1 stimulation.
      CONCLUSION: These results suggest that osteosclerosis in IMF may be related to
      overproduction of OPG and enhanced level of OPG is not due to the effect of TGF
      beta1 on the BMS cells. It could be due to the effect of TGF-beta1 or other
      growth factors on cells other than BMS cells such as the osteoblasts.

PMID- 15504546
TI  - In human immature BFU-E tumor necrosis factor-alpha not only downregulates CDK6
      but also directly produces apoptosis which is prevented by stem cell factor.
AB  - OBJECTIVE: The aim of this study was to reveal the mechanisms by which tumor
      necrosis factor-alpha (TNF-alpha) inhibits immature human day-4 burst-forming
      units-erythroid (BFU-E) and the effect of stem cell factor (SCF) on this process.
      METHODS: Sequential density-gradient centrifugation, depletion of lymphocytes,
      removal of adherent cells, and negative selection with CD2, CD11b, CD16, and CD45
      monoclonal antibodies were used to purify day-1 BFU-E, which were then incubated
      for 3 days to generate day-4 cells. The day-4 cells were incubated with TNF
      alpha, and/or SCF, and the extent of apoptosis was gauged by morphologic
      observations, TUNEL assays, and Western blots. RESULTS: The cell number and the
      number and size of erythroid colonies were significantly reduced when day-4 cells
      were incubated with TNF-alpha. Apoptosis was observed in single-cell plasma clot
      assays. TUNEL assays showed 20% +/- 6% apoptotic cells with TNF-alpha while
      controls had 2.8% +/- 2.2%. Caspases 3 and 8 were strongly activated while the
      amount of CDK6 was reduced by TNF-alpha. When SCF, a potent stimulator of cell
      growth, was added with TNF-alpha, cell growth inhibition was reduced and the
      apoptotic cells decreased to 0.9% +/- 1.2%. The activations of caspase 3 and
      caspase 8 were almost completely blocked by SCF while CDK6 and the FLICE
      inhibitory protein (FLIP) were increased. CONCLUSIONS: Our results indicate that
      in immature human BFU-E, TNF-alpha downregulates CDK6 but also directly produces
      apoptosis which is prevented by SCF.

PMID- 15504547
TI  - Water-soluble extracts from Angelica acutiloba Kitagawa enhance hematopoiesis by
      activating immature erythroid cells in mice with 5-fluorouracil-induced anemia.
AB  - The extract from the root of Angelica acutiloba Kitagawa (AR), which is used as
      herbal medicine in Japan, has been reported to be clinically effective for
      postmenstrual blood loss and erythropoietin (EPO)-resistant anemia in chronic
      renal failure, although the pharmacological mechanisms underlying its clinical
      efficacy are unknown. We prepared an animal model of anemia by bolus injection of
      5-fluorouracil (5FU) at 150 mg/kg to mice (8- to 12-week-old female C57BL/6J),
      and then administered orally the water-soluble fraction of AR to the anemic mice
      for 10 days. After confirming the anti-anemic effect of the water-soluble
      fraction of AR (AR-3) containing polysaccharides, we examined the effects of AR-3
      on immature erythroid cell activity, EPO production, and plasma cytokine levels.
      AR-3 administration at 50 mg/kg activated erythroid progenitor cells in bone
      marrow on day 10, increased the percentage of peripheral reticulocytes in red
      blood cells on day 15, and led to the recovery of red blood cell count to a value
      that was almost equal to the basal level on day 20. Although EPO production,
      which was determined by examining EPO mRNA expression in kidney and liver,
      remained unaltered by AR-3 administration, this treatment significantly lowered
      plasma interferon-gamma level, which may suppress the activity of erythroid
      progenitor cells. These results suggest that the polysaccharides in AR promote
      hematopoiesis by activating immature erythroid cells, in part, by suppressing
      cytokine secretion. Since the hematopoietic effect was achieved by high-dose AR
      3, identification of specific polysaccharides is still required for the
      development of a novel medicine for anemia caused by a malignancy or
      chemotherapy.

PMID- 15504548
TI  - Modulation of the expression and activity of cyclooxygenases in normal and
      accelerated erythropoiesis.
AB  - OBJECTIVE: The present study was aimed at characterizing the expression and
      activity of cyclooxygenase (COX) isoenzymes in erythropoiesis. METHODS: The
      expression and activity of cyclooxygenase (COX) and prostaglandin (PG) synthases
      were investigated in: 1) erythroblasts developed in culture from human CD34(+)
      hematopoietic progenitors, 2) erythroblasts in bone marrow specimens, and 3)
      peripheral erythrocytes isolated from healthy donors and from patients with a
      high regeneration rate of erythrocytes. RESULTS: While COX-1 protein was observed
      at each stage of erythroblast development, COX-2 protein was induced at later
      stages through a p38/MAPK-dependent pathway. Both COX isoforms were also observed
      in mature erythroblasts of the bone marrow. Erythroblasts developed in culture
      synthesized significantly more PGE(2) than TXB(2) and indomethacin delayed
      erythroid maturation. COX-1 and COX-2 were also observed in erythrocytes by
      immunostainings, although COX expression was confined to a fraction of
      circulating erythrocytes. Peripheral erythrocytes synthesized low but detectable
      amounts of PGE(2) and TXB(2). Similarly to erythroblast progenitors, PGE(2) was
      the prevalent prostanoid released by erythrocytes. This biosynthetic capacity was
      significantly increased in erythrocytes from patients with accelerated
      erythropoiesis as compared to controls. CONCLUSIONS: Both COX isoforms are
      present and enzymatically active during human erythropoiesis, although with
      different kinetics, and COX-derived prostanoids may play a role in erythroid
      maturation. Furthermore, peripheral erythrocytes retain in part the capacity of
      expressing COX and synthesizing prostanoids, which may contribute to the
      hemostatic/thrombotic response to vascular injury in different diseases,
      including congenital hemolytic disorders.

PMID- 15504549
TI  - Activated Fps/Fes tyrosine kinase regulates erythroid differentiation and
      survival.
AB  - OBJECTIVE: A substantial body of evidence implicates the cytoplasmic protein
      tyrosine kinase Fps/Fes in regulation of myeloid differentiation and survival. In
      this study we wished to determine if Fps/Fes also plays a role in the regulation
      of erythropoiesis. METHODS: Mice tissue-specifically expressing a "gain-of
      function" mutant fps/fes transgene (fps(MF)) encoding an activated variant of
      Fps/Fes (MFps), were used to explore the in vivo biological role of Fps/Fes.
      Erythropoiesis in these mice was assessed by hematological analysis, lineage
      marker analysis, bone-marrow colony assays, and biochemical approaches. RESULTS:
      fps(MF) mice displayed reductions in peripheral red cell counts. However, there
      was an accumulation of immature erythroid precursors, which displayed increased
      survival. Fps/Fes and the related Fer kinase were both detected in early
      erythroid progenitors/blasts and in mature red cells. Fps/Fes was also activated
      in response to erythropoietin (EPO) and stem cell factor (SCF), two critical
      factors in erythroid development. In addition, increased Stat5A/B activation and
      reduced Erk1/2 phosphorylation was observed in fps(MF) primary erythroid cells in
      response to EPO or SCF, respectively. CONCLUSIONS: These data support a role for
      Fps/Fes in regulating the survival and differentiation of erythroid cells through
      modulation of Stat5A/B and Erk kinase pathways induced by EPO and SCF. The
      increased numbers and survival of erythroid progenitors from fps(MF) mice, and
      their differential responsiveness to SCF and EPO, implicates Fps/Fes in the
      commitment of multilineage progenitors to the erythroid lineage. The anemic
      phenotype in fps(MF) mice suggests that downregulation of Fps/Fes activity might
      be required for terminal erythroid differentiation.

PMID- 15504550
TI  - Graft facilitating cells are derived from hematopoietic stem cells and
      functionally require CD3, but are distinct from T lymphocytes.
AB  - OBJECTIVE: We previously demonstrated that CD8(+)/TCR(-) bone marrow cells
      facilitate engraftment of HSC in allogeneic recipients without causing graft-vs
      host disease. Whether facilitating cells (FC) develop from T cells or represent a
      distinct lineage has not been determined. METHODS: In the present studies, we
      characterized the lineage derivation of FC, defined the role for the CD3 complex
      in allogeneic facilitation, and demonstrated syngeneic facilitation by FC but not
      T cells. RESULTS: We demonstrate for the first time that FC development and
      function is independent of T cells and cannot be replaced by them. Purified
      GFP(+) HSC transplanted in syngeneic recipients produce GFP(+) FC, which
      facilitate in secondary transplants, confirming that FC are derived from HSC. In
      addition, FC, but not T cells, potently facilitate the engraftment of suboptimal
      numbers of HSC in syngeneic recipients. Notably, FC contain the transcripts for
      CD3 epsilon and CD3 delta, but not TCR alpha or TCR beta, excluding the
      possibility of T-cell contamination. Genetic mutations that generate a functional
      deficiency in CD3 signaling significantly impair FC function in allogeneic
      facilitation (p=0.006). CONCLUSION: Taken together, these data clearly
      distinguish FC from T cells. Moreover, they indicate that FC require the CD3
      epsilon gene to facilitate allogeneic HSC engraftment. The unique function(s) of
      FC make them an attractive focus for new cell-based therapeutic approaches to
      enhance HSC engraftment while reducing toxicity, especially when limiting numbers
      of HSC are available.

PMID- 15504551
TI  - Hepatocyte growth factor plays roles in the induction and autocrine maintenance
      of bone marrow stromal cell IL-11, SDF-1 alpha, and stem cell factor.
AB  - OBJECTIVE: Bone marrow (BM) stroma provides the microenvironment required for
      long-term hematopoiesis, and this is supported by direct interaction between
      stromal cells and hematopoietic cells, mediated by adhesion molecules, and
      through cytokine releases from the BM stroma. In a previous study, we
      demonstrated that hepatocyte growth factor (HGF) is one of the cytokines
      constitutively produced from BM stromal cells, promoting hematopoiesis mainly in
      an indirect way. We also showed that stromal cells themselves express HGF
      receptor c-MET. It was therefore postulated that HGF exerts its effect on
      hematopoiesis and maintenance of the hematopoietic microenvironment in a
      paracrine and autocrine manner. METHODS: The effect of HGF on stromal cells was
      analyzed by neutralizing intrinsic HGF. RESULTS: Addition of neutralizing anti
      HGF antibody inhibited the ability of BM stromal cells to support colony
      formation from CD34(+) cells and reduced production of significant cytokines from
      stromal cells, interleukin-11 (IL-11), stromal cell-derived factor-1 alpha (SDF-1
      alpha), and to a lesser extent, stem cell factor (SCF). Furthermore, this
      neutralizing antibody reduced proliferation of stromal cells and inhibited
      adhesion of stromal cells to collagen type IV and fibronectin. Inhibition of
      adhesion to fibronectin was mediated by inhibition of alpha(5)beta(1)-integrin.
      CONCLUSION: These findings indicate that HGF constitutively produced from BM
      stromal cells is an autocrine regulator, which is able to maintain the
      hematopoietic microenvironment through stimulating proliferation and adhesion to
      the extracellular matrix and promoting hematopoiesis through inducing
      constitutive production of IL-11, SDF-1 alpha, and SCF by stromal cells
      themselves.

PMID- 15504552
TI  - Ganciclovir-mediated elimination of HSV-Tk+ T cells and cure of graft-vs-host
      disease in an allogeneic bone marrow transplantation model in the rat.
AB  - OBJECTIVE: Suicide gene therapy for leukemia aims to benefit from T cells in the
      BM graft, by reducing the probability of leukemia relapse (GVL), while severe
      complications of graft-vs-host disease (GVHD) may be avoided. In an allogeneic
      rat BMT model we defined the conditions to induce a lethal GVHD with HSV-Tk gene
      transduced T cells. We studied the feasibility to rescue the animals by
      conditional elimination of the T cells with ganciclovir (GCV) treatment. METHODS:
      Allogeneic T cells transduced with a retroviral vector encoding the HSV-Tk
      suicide gene were added in varying numbers to a BM graft. Expression of HSV-Tk
      strongly increases the cytolytic effect of GCV, thereby allowing elimination of
      overreactive T cells at will. Various experimental conditions were tested in the
      rat model. RESULTS: A relation between the number of HSV-Tk(+) T cells added to
      the BM graft and GVHD development was found. GCV treatment resulted in selective
      HSV-Tk(+) T-cell elimination in blood and tissues but not in abrogation of GVHD
      due to persistence of HSV-Tk(-) T cells. T cells in unmanipulated rat BM normally
      have a low risk to induce GVH but when they are administered in combination with
      high numbers of HSV-Tk(+) T cells there is an apparent increase in their GVH
      inducing potential. When HSV-Tk(+) T cells are added to T cell-depleted BM a
      consequently developing GVH can be controlled by GCV treatment with 60-70% of the
      animals surviving. CONCLUSIONS: We show that T cell-mediated suicide gene therapy
      within the context of allo-BMT can be applied with success. The apparent
      limitation in the number of transduced as well as nontransduced T cells that can
      be safely added to the BM graft should be taken into consideration when designing
      human suicide gene therapy protocols.

PMID- 15504553
TI  - Molecular insights into the pleiotropic effects of plasma on ex vivo-expanded T
      cells using DNA-microarray analysis.
AB  - OBJECTIVE: Immunotherapy with ex vivo-expanded T cells depends on a large supply
      of biologically active cells. Understanding the effects of culture parameters is
      essential for improving cell expansion and efficacy. We used DNA-microarray and
      flow-cytometric analysis coupled with functional assays to investigate
      mechanistic aspects of plasma supplementation in ex vivo T-cell expansion.
      METHODS: The effect of plasma supplementation on 18 primary T-cell cultures over
      a 15-day expansion was investigated. Transcriptional analysis of 5 samples was
      done with time points every 2 to 3 days throughout the 15-day expansion.
      Quantitative RT-PCR analysis was used to confirm selected microarray data. The
      expression of granzyme A and vimentin were analyzed using intracellular flow
      cytometry. T-cell functionality was assessed using a mixed leukocyte reaction
      (MLR). RESULTS: We show that the increased expansion of plasma-supplemented
      cultures of primary human T cells is mostly due to increased cell survival. T
      cells from plasma-supplemented cultures show higher expression of immunoglobulin
      genes, integrins, and genes of cytotoxic granules, suggesting a possible enhanced
      immune function. This was confirmed using a mixed leukocyte reaction and
      intracellular granzyme-A measurements. A distinct gene expression pattern was
      correlated to viability differences between plasma-supplemented and serum-free
      cultures. Ontological analysis of genes in this pattern suggests that the
      decreased viability of serum-free cultures correlates with higher expression of
      actin-cytoskeleton and lipid-metabolism genes. Vimentin was found to be expressed
      higher in serum-free cultures. CONCLUSIONS: These results indicate that the
      observed decreased cytotoxicity of T cells cultured in serum-free media may be
      due to increased oxidative stress and cytoskeleton degradation.

PMID- 15504554
TI  - Expression of protease activated receptor 3 (PAR3) is upregulated by induction of
      megakaryocyte phenotype in human erythroleukemia (HEL) cells.
AB  - OBJECTIVE: Two major protease-activated receptors (PARs), PAR1 and PAR4, are
      involved in the activation of human platelets by thrombin. A third, PAR3, is
      preferentially expressed by tissues of hematopoietic origin and megakaryocytes.
      Although PAR3 is also a thrombin substrate, its low-level expression on human
      platelets suggests a function distinct from that of PAR1, the major receptor
      involved in thrombin-mediated platelet activation. We studied the expression of
      PARs during megakaryocyte differentiation of human erythroleukemia (HEL) cells in
      order to determine the role of PAR3 in megakaryocytopoiesis. METHODS: HEL cells
      exposed to phorbol 12-myristate 13-acetate (PMA) to induce megakaryocyte
      differentiation were examined by light microscopy and flow cytometry (DNA ploidy,
      surface expression of PAR1, PAR3, GPIIb-IIIa). Northern blot, RT-PCR, and
      quantitative RT-PCR were used to evaluate the expression of PARs 1, 3, and 4
      mRNA. HEL cells were also exposed to thrombin and thrombopoietin (TPO). RESULTS:
      In baseline studies, unstimulated HEL cells were found to express comparable
      levels of PAR1 and PAR3 by Northern blot. Minimal expression of PAR4 was detected
      by RT-PCR, but not by Northern analysis. Exposure to PMA, but not thrombin or
      TPO, resulted in megakaryocytic differentiation as evident by increased cell size
      and nuclear complexity, increased ploidy, and enhanced expression of GPIIb-IIIa,
      a specific marker of megakaryocytes/platelets. PMA-stimulated HEL cells showed
      enhanced PAR3 cell-surface expression (approximately threefold increase by day 2)
      by flow cytometry. In contrast, there was no change in cell-surface PAR1
      expression. Northern blot analysis (approximately 10-fold) and quantitative RT
      PCR (approximately threefold) confirmed the upregulation of PAR3 mRNA expression
      (by 24 hours) in cells exposed to PMA. This did not occur with exposure to TPO.
      CONCLUSION: These data demonstrate increased expression of PAR3 mRNA and protein
      in HEL cells undergoing megakaryocytic maturation following PMA exposure,
      suggesting a developmental role for PAR3. Furthermore, regulation of PAR3
      expression appears to be specifically coupled to the protein kinase C system, but
      independent of the Ras/Raf/MAP kinase pathway.

PMID- 15504555
TI  - Cytokine requirements differ for stroma and embryoid body-mediated hematopoiesis
      from human embryonic stem cells.
AB  - OBJECTIVE: Human embryonic stem (ES) cells can be induced to differentiate into
      hematopoietic lineages either by stromal cell coculture or by formation of
      embryoid bodies (EBs). Here, we better characterize cell-bound and secreted
      factors that support this hematopoietic development. METHODS: Human ES cells
      either cocultured on the mouse bone marrow cell line S17, or allowed to form EBs,
      were induced to differentiate in the presence of serum, serum-free conditions,
      and serum-free media supplemented with defined cytokines. To better characterize
      the requirement for stromal cell-bound or secreted proteins, S17 conditioned
      media and transwell cultures were also utilized. RESULTS: In both models,
      CD34(+), CD45(+), and hematopoietic colony-forming cells (CFCs) were routinely
      derived. While hematopoietic development was diminished without serum, here we
      demonstrate with the stromal cell coculture model that addition of the growth
      factors stem cell factor (SCF), thrombopoietin (TPO), and Flt-3 ligand (Flt3L) to
      serum-free media does allow isolation of hematopoietic progenitors. However,
      these same three growth factors added to serum-free media do not support
      significant hematopoiesis in the EB system. However, addition of the mesoderm
      inducing factors bone morphogenic protein-4 and vascular endothelial growth
      factor to EBs grown in serum-free media plus SCF, TPO, and Flt-3L does improve
      hematopoietic development. CONCLUSION: These results demonstrate the utility of
      human ES cell to evaluate specific stimuli that regulate cell fate decisions and
      the survival of specific lineages. Moreover, the method used to promote
      differentiation of ES cells may alter the cytokines or growth factors required to
      isolate specific cell types.

PMID- 15504557
TI  - The last genius? -- reflections on the death of Francis Crick.

PMID- 15504556
TI  - Molecular TCR diagnostics can be used to identify shared clonotypes after
      allogeneic hematopoietic stem cell transplantation.
AB  - OBJECTIVE: In allogeneic hematopoietic stem cell (HSCT) transplantation, recovery
      of the T cell receptor (TCR) repertoire depends upon the composition of the graft
      and is modulated by peri-transplant immunosuppression, viral infections, and
      graft-vs-host disease (GVHD). We hypothesized that after allogeneic HSCT,
      molecular analysis of the TCR repertoire can be used to identify and quantitate
      immunodominant T cell clones that may play a role in GVHD or other clinical
      events. METHODS: We utilized a rational strategy for the analysis of the expanded
      CTL clones. First, we studied the VB spectrum in a cohort of patients who had
      received either matched sibling or unrelated donor grafts. The CDR3 sequences of
      immunodominant clones were identified and clonotypic PCR and sequencing was
      applied to determine the level of clonotype sharing. RESULTS: Significant
      expansions of VB families were observed following transplantations; 61% were
      oligo/monoclonal. Immunodeficiency was reflected by depletion of multiple VB
      families from both the CD8 and CD4 repertoires. The level of sharing varied
      between clonotypes, suggesting that some antigens have a more "public" spectrum
      while others are restricted to specific patients. Immunodominant CDR3 sequences
      common to allogeneic HSCT, healthy controls, and other conditions were
      identified. CONCLUSION: The clonotypes of expanded CTL clones may reflect
      responses to alloantigens (e.g., in correlation with clinical GVHD) or pathogens.
      In the future, molecular T cell diagnostics may become a powerful clinical tool
      in transplantation to monitor disease and to direct treatment.

PMID- 15504558
TI  - Infant mouthing behavior: the immunocalibration hypothesis.
AB  - Avid mouthing, the propensity of infants to suck objects and put them in their
      mouths, is a pattern characteristic of the first 2-3 years of life, with its most
      intensive manifestation occurring during the first year. Although traditional
      accounts explain infant mouthing as a source of sensual gratification and/or
      environmental exploration, these proximate hypotheses are inconsistent with the
      high costs of mouthing, including choking, poisoning, and exposure to pathogens.
      We propose that mouthing serves to proactively expose the naive gastrointestinal
      tract to environmental antigens and commensal bacteria while under the sheltering
      umbrella of breastfeeding. Mouthing functions to accurately calibrate the
      developing immune system, including antibody production and mucosal immunity, to
      the local disease ecology. The critical exposure period is not open-ended, as
      failure to expose the gut to an adequate number of antigens early in life is
      associated with an increased risk of allergies, asthma, and atopy. Weaning
      initiates a number of immune changes that may program the neonatal immune system
      into certain life-long responses.

PMID- 15504559
TI  - Evolutionary legacy: form of ingestion, not quantity, is the key factor in
      producing the effects of sugar on human health.
AB  - Tens of dietary trials have been conducted to investigate the metabolic effects
      of sugar (sucrose) and its impact on human health. All of those studies took into
      account only the quantity of ingested sugar. By contrast, not a single study
      attempted to assess whether the form in which sugar is consumed plays a role in
      producing its metabolic effects. The failure of cohorts of researchers to specify
      how they administered sugar in their dietary trials may well explain why the
      results of those studies are extremely contradictory. These discrepant findings,
      understandably, resulted in conflicting opinions about sugar and in divergent
      guidelines about its recommended consumption. The evolutionary line of reasoning
      expounded in this article leads to conclude that the form in which sugar is
      ingested, not its quantity, constitutes the most important factor in producing
      the metabolic effects of sugar and its impact on human health. As a consequence,
      for example, the consumption of 100 g of sugar per day can be either detrimental
      or innocuous, depending on the form in which sugar is ingested. Specifically, the
      evolutionary hypothesis advanced in this paper implies that sugar can predispose
      to type 2 diabetes and can cause unhealthy changes in blood lipids if it is
      consumed in solid forms or in dense solutions containing more than 250 g/L,
      whereas sugar is harmless if it is consumed in more dilute concentrations. This
      evolutionary hypothesis, in view of its intuitively far-reaching clinical
      implications, should be tested by at least one dietary trial.

PMID- 15504560
TI  - Pineal attrition, loss of cognitive plasticity, and onset of puberty during the
      teen years: is it a modern maladaptation exposed by evolutionary displacement?
AB  - Cognitive plasticity, a developmental trait that promotes acquisition of complex
      skills such as language or playing musical instruments, diminishes substantially
      during puberty. The loss of plasticity has been attributed to surge of sex
      steroids during adolescence, but the phenomenon remains poorly understood. We
      hypothesize that pineal involution during puberty may contribute to plasticity
      decay. The pineal gland produces melatonin, the level of which declines
      dramatically during onset of puberty. Emerging evidence suggest that melatonin
      may modulate cognitive plasticity, independent of the effects of sex steroids,
      and low sex steroids and high melatonin may be simultaneously required to
      maintain cognitive plasticity. Potential mechanisms by which melatonin may
      modulate plasticity are examined within the sleep and hippocampal long-term
      potentiation frameworks. Implications for psychiatric conditions that involve
      sleep disorders and learning dysfunctions such as schizophrenia and autism are
      discussed, and the potential adaptive roles of postprandial and postcoital sleep
      are explored. From the Darwinian perspective, development and reproductive
      maturity may represent distinct phases that require tailored cognitive strategies
      to maximize fitness. While cognitive flexibility and susceptibility to new skills
      may be paramount during development, reduced cognitive flexibility and increased
      cognitive determinism may enable more efficient responses to stimuli during
      adulthood. Thus, cognitive plasticity and cognitive determinism may represent
      trade-off adaptations and different dimensions of intelligence. The decline of
      plasticity and emergence of puberty during the second decade may be relics of
      prehistoric times when the human lifespan was short and the environment was
      relatively simple and static. Today, when the environment is more complex and
      dynamic, and humans are living far longer, the early obsolescence of plasticity
      during puberty may represent a Darwinian inefficiency exposed by evolutionary
      displacement. Regulation of plasticity may be a systemic phenomenon, as
      exemplified by the association of learning disability with allergic conditions, a
      form of immune plasticity dysfunction. Ramifications for other plastic functions
      that decline during puberty such as wound healing and hyaline cartilage
      regeneration are explored. Like the plasticity of immunity and cognition, the
      plasticity of hyaline cartilage during youth may enable hosts to respond to
      ecologic opportunities and generate the optimally adapted adult phenotype. Pineal
      involution may represent a potential target for therapeutic extension or
      restoration of plasticity after puberty. Extending plasticity may have far
      reaching consequences for human evolution.

PMID- 15504561
TI  - Seven fundamental, unsolved questions in molecular biology. Cooperative storage
      and bi-directional transfer of biological information by nucleic acids and
      proteins: an alternative to "central dogma".
AB  - The Human Genome Mapping Project provided us a large amount of sequence data.
      However our understanding of these data did not grow proportionally, because old
      dogmas still set the limits of our thinking. The gene-centric, reductionistical
      side of molecular biology is reviewed and seven problems are formulated, each
      indicating the insufficiency of the "central dogma". The following is concluded
      and suggested: 1. Genes are located and expressed on both DNA strands; 2. Introns
      are the source of important biological regulation and diversity; 3. Repeats are
      the frame of the chromatin structure and participate in the chromatin regulation;
      4. The molecular accessibility of the canonical dsDNA structure is poor; 5. The
      genetic code is co-evolved with the amino acids and there is a stereochemical
      matching between the codes andamino acids; 6. The flow of information between
      nucleic acids and proteins is bi-directional and reverse translation might exist;
      7. Complex genetic information is always carried and stored by nucleic acids and
      proteins together.

PMID- 15504562
TI  - Episodic memory and the hippocampus: another view.
AB  - A popular view of the function of the hippocampus maintains that this structure
      temporarily encodes the neocortical representation of the experience of an
      episode. It uses the encoding to recreate repeatedly the neocortical
      representation. It is said that in time the episodic memory becomes consolidated
      in the neocortex and can be retrieved independent of the hippocampus. This paper
      is critical of that view and begins by raising four concerns. These include a
      question of how the hippocampus could encode the rich complexity of neocortical
      representations in sufficient detail to recreate them. And it observes that some
      data indicate episodic memories remain dependent on the hippocampus for life.
      Another view of hippocampal function is presented which addresses these concerns.
      Basically, this view hypothesizes that the ability to retrieve episodic memories
      involves the interplay between two modes of hippocampal function. Processes
      during the theta mode facilitate the development of context memory in the
      hippocampus and the registration of unique events in the neocortex, but block the
      influence of context memory upon the neocortex. By contrast, during the non-theta
      mode, context memory is projected onto the neocortex, creating a contextual
      framework. It is proposed that the ability to retrieve memory of episodes depends
      on the development, through contiguity, of associations between the
      representation of the episode (created during theta) and a contextual framework
      (evoked during non-theta). From this perspective, the episode does not need to be
      encoded in the hippocampus, but remains dependent indefinitely on associations
      formed between the episodic memory in the neocortex and a context memory
      maintained in hippocampal structures. However, for the associations that enable
      retrieval to form, the creation of the representation of an episode during theta
      must be followed quickly by the evocation of a contextual framework. During an
      extended period of the theta mode as occurs during REM sleep dreaming, these
      associations cannot usually be formed, resulting in amnesia for most dreams.

PMID- 15504563
TI  - Psychotherapy as assisted homeostasis: activation of emotional processing
      mediated by the anterior cingulate cortex.
AB  - Although psychotherapy is successful in altering emotional distress, the
      biological mechanism by which it achieves this has not been the subject of
      intensive neurobiological investigation. Mindful processing of emotion has been
      proposed [Mindfulness-Based Cognitive Therapy for Depression, The Guilford Press,
      New York, 2002] to be a key factor in prevention of relapse in depressive illness
      and here that hypothesis is developed and extended to include other conditions in
      which emotion processing may be obstructed or dysregulated. Cognitive therapy,
      interpersonal psychotherapy, psycho-dynamic psychotherapy and dialectical
      behaviour therapy, each in a different way and with a distinct emphasis,
      encourage awareness of emotions and their associated cognitions and biographies,
      and their varying success may depend on the degree to which they achieve
      activation of internal healing processes. In eye movement desensitisation and
      reprocessing (EMDR), the selected target is formatted for endogenous processing
      which is facilitated and accelerated by eye movements or alternating bilateral
      auditory or tactile stimulation. The ability to sustain focussed attention on the
      affect and its visceral, cognitive and biographical components is postulated to
      activate a homeostatic process of distress resolution, seen most clearly in
      treatment of post-traumatic stress disorder (PTSD) with EMDR, in which resolution
      of distress can be intense and rapid while therapist input is non-directive,
      although supportive, empathic, and non-judgemental. Once the therapist has helped
      to frame the questions, the patient's brain will find the answers needed for the
      resolution of the distress and all the components of the traumatic event, whether
      visceral, cognitive, affective or interpersonal. The anterior cingulate cortex,
      especially the dorsal and rostral components, is suggested to be the key
      neurobiological substrate for the efficacious psychotherapeutic relief of
      distress, and relevant functional neuroimaging studies are summarised. One
      limitation of some previous imaging studies of emotion is that they have tended
      to use mild stimuli to discrete emotions. An alternative approach would be to
      image the brain during reprocessing of an unpleasant event which has profoundly
      affected the person so that the associated intense emotions could be clearly
      labelled and correlated with changes in regional brain functioning.

PMID- 15504564
TI  - Selective brain cooling seems to be a mechanism leading to human craniofacial
      diversity observed in different geographical regions.
AB  - Selective brain cooling (SBC) can occur in hyperthermic humans despite the fact
      that humans have no carotid rete, a vascular structure that facilitates
      countercurrent heat exchange located at the base of the skull in some mammals.
      Emissary and angular veins, upper respiratory tract, tympanic cavity and
      cerebrospinal fluid are major components of SBC system in humans. The efficiency
      of SBC is increased by evaporation of sweat on the head and by ventilation
      through the nose, but it is surprising to find out that mammals do not display
      SBC during exercise hyperthermia. What is the explanation then for the SBC at
      high body temperatures? Our hypothesis is that selective brain cooling protects
      the brain from thermal damage in a long-standing manner by allowing adaptive
      mechanisms to change the craniofacial morphology appropriate for different
      environmental conditions. Since the brain can only be as big that can cool, it is
      not surprising to find a lower (below 1300 cm(3)) cranial volume in Australian
      Aborigines with respect to the one (over 1450 cm(3)) in Eskimos. In addition to
      lower brain volume, other craniofacial features such as thick everted lips,
      broader nasal cavity and bigger paranasal sinuses that provide more evaporating
      surfaces seem to be anatomical variations developed in time for an effective SBC
      in hot climates. It was reported previously that these biological adaptations
      result from the tissues of neural crest origin. Among the crest derivatives,
      leptomeninges (pia and arachnoid mater), skeletal and connective tissues of the
      face and much of the skull seem to be structures upon which environment operates
      to produce more convenient craniofacial morphology for an effective SBC. In
      conclusion, selective brain cooling seems to be a mechanism leading to adaptive
      craniofacial diversity observed in different geographical regions. Thus, SBC is
      necessary for long-term biological adaptation, not for protecting the brain from
      acute thermal damage.

PMID- 15504565
TI  - The role of altered impedance in the pathophysiology of normal pressure
      hydrocephalus, Alzheimer's disease and syringomyelia.
AB  - Normal pressure hydrocephalus, Alzheimer's disease and syringomyelia appear to be
      completely unrelated diseases, however, they share a reduction in subarachnoid
      space compliance as part of their pathophysiology. This paper discusses the
      physiology of pulsatile fluid flow and its relationship to compliance/impedance.
      Unlike continuous or non-pulsatile flow where the vessel resistance and pressure
      gradient are the major determinants of the volume of fluid flowing, when the
      fluid flow in a vessel pulsates then the vessel compliance/impedance becomes
      important. A reduction in compliance in the craniospinal cavity in each of the
      three diseases discussed, leads to a limitation of the outflow vessel compliance.
      Therefore, there is an increase in outflow vessel impedance. The venous blood,
      CSF and interstitial brain/spinal cord fluid all have significantly pulsatile
      flow and an increase in the impedance of the fluid outflow in each disease would
      limit the volume of these fluids as they attempt to cross the subarachnoid space.
      It is hypothesised that a reduction in the efficiency of the outflow of venous
      blood, CSF and interstitial brain/spinal cord fluid would lead to the
      accumulation of CSF in NPH, cord fluid in syringomyelia and delay the excretion
      of beta amyloid via the interstitial drainage pathways in AD.

PMID- 15504566
TI  - Is cancer just an incurable infectious disease?
AB  - The word 'cancer' is of Latin derivation and means crab. By the turn of the 20th
      Century organized medicine had come to the conclusion that it was not a matter of
      whether infectious disease caused cancer, but which one. For over two hundred
      years a cancer germ had been discovered and rediscovered, named and renamed, each
      scientist adding to the knowledge, but to no avail. Then, in 1910, certain
      American medical powers did a 180-degree rotation, deciding that cancer was not
      caused by a microbe, and that anyone who thought otherwise was a heretic, a
      charlatan or a quack. But Dr. Virginia Livingston and her network were none of
      the above, their meticulous peer-reviewed research and publications, done at the
      height of US post World War II technology. And Dean Burk, Head of Cell Chemistry
      at the NCI went so far as to say that Livingston's cancer germ was as real and
      certain as anything known about cancer. Researcher, MD Alan Cantwell Jr. grew up
      thinking that all germs responsible for the important diseases were supposed to
      have already been discovered. But much to his dismay, he found one that was left
      out: the cancer germ. Cantwell already knew that for finding this, Livingston had
      already been branded by traditional medicine, leaving what he thought to be
      perhaps the major discovery of the 20th century largely discredited. The striking
      analogy between cancer and tuberculosis was noticed long before the tubercle
      bacillus was discovered. In 1877, Sir John Simon clearly pointed out the
      similarity and in fact argued very strongly in favor of a microbial origin for
      cancer. But Simon's vindication would have to wait for Livingston's germ, which
      although tuberculosis-like, was not tuberculosis but an atypical form of this
      mycobacterium, melded from the mycobacterium and other related Actinomycetales.
      Had medical science and the powers that be spent as much time in investigating
      and destroying Livingston's germ as they did in attacking her and those around
      her, cancer might be curable today.

PMID- 15504567
TI  - The arterial circle of Willis of the mouse helps to decipher secrets of cerebral
      vascular accidents in the human.
AB  - The human brain represents an elaborate product of hominizing evolution.
      Likewise, its supporting vasculature may also embody evolutionary consequences.
      Thus, it is conceivable that the human tendency to develop cerebral vascular
      accidents (CVAs) might represent a disease of hominization. In a search for
      hominizing changes on the arterial circle of Willis (hWAC), we attempted an
      anatomical comparison of the hWAC with that of the mouse (mWAC) by injecting
      aliquots of resin into the vasculature of the mouse and then creating vascular
      endocasts of the mWAC. The internal carotid artery of the mouse (mICA) unites
      with the mWAC midway between the middle cerebral artery (mMCA) and posterior
      cerebral artery (mPCA). The mWAC does not complete a circle: the mWAC nourishes
      the anterior portion of the circle which branches out to the olfactory artery
      (OlfA) and mPCA, along with the mMCA, and the basilar artery (mBA) does not
      connect to the mPCA. The OlfA is thicker than the mMCA. The relative brain weight
      of the mouse was 74 g on average for a 60 kg male and 86 g for a 60 kg female,
      respectively, as compared with 1424 g for a 60 kg man. These findings are
      consistent with the mouse being a nocturnal carnivore that lives on olfactory
      information in contrast to the human that lives diurnally and depends on visual
      and auditory information. In man, the human ICA (hICA) unites with the hWAC at a
      point where the human middle cerebral artery (hMCA) branches out, and thus, blood
      from the hICA does not flow through the hWAC but drains into the hMCA directly.
      The hMCA is thicker than the anterior cerebral artery. The hPCA receives blood
      from the hBA rather than from the hICA, and thus, the entire hWAC forms a closed
      circuit. Since the hICA drains directly into the hMCA without flowing a distance
      through the hWAC, the capacitor and equalizer functions of the WAC will be
      mitigated so much that the resultant hemodynamic changes would render the hMCA
      more likely to contribute to CVAs. Thus, anatomical findings and possibly
      functions of the arterial circle of Willi may vary from one species to another,
      depending on one's specific cerebral evolution.

PMID- 15504569
TI  - Hypothesis about the physiopathology of acute deterioration and sudden death
      caused by colloid cysts of the third ventricle.
AB  - In this paper, the authors review the mechanisms of acute deterioration and
      sudden death caused by colloid cysts (CCs). These dreaded events are widely
      recognized complications of CC, however the mechanism(s) in cause has been
      subject to controversy. Increased intracranial pressure (ICP) is a common event
      associated with many cerebral disorders, including colloid cysts, though
      compensatory mechanisms may allow ICP to remain at normal levels. However, a
      compensated system might decompensate for many factors such as intracranial
      haemorrhage, acute hydrocephalus, brain oedema, or an increase in sagittal sinus
      pressure (SSP). The sagittal sinus in adults with brain tumours appears to
      respond unpredictably when ICP increases and in some patients, when ICP increased
      the SSP increased too due to the fact that their sinuses collapse. We therefore
      speculate that the mechanism of acute deterioration and sudden death is a
      multifactorial and dynamic process, in which the increase in sagittal sinus
      pressure would appear to be an important element. It seems possible that acute
      deterioration is initiated by an increase in sagittal sinus pressure, which
      provokes acute brain swelling, with a series of often-irreversible events,
      leading to sudden death. Since the majority of cases of acute deterioration and
      death are due to CCs of the third ventricle, the authors suggest that surgical
      resection should be carried out on diagnosed CCs measuring over 1 cm, because
      sudden death has not been reported as having been caused by colloid cysts
      measuring less than this dimension.

PMID- 15504568
TI  - Calcium and vitamin D supplementation during bisphosphonate administration may
      increase osteoclastic activity in patients with bone metastasis.
AB  - Bone metastasis are a frequent complication of cancer, occurring in up to 70% of
      patients with advanced breast or prostate cancer. The consequences of bone
      metastasis are often devastating. Osteolytic metastasis can cause different kinds
      of skeletal related events including severe pain, pathologic fractures, life
      threatening hypercalcemia, spinal cord compression, and other nerve-compression
      syndromes. These skeletal-related events are the result of the resorption of
      mineralized bone by osteoclasts. Bisphosphonates are synthetic analogues of
      naturally occurring pyrophosphate compounds that inhibit bone resorption. Potent
      bisphosphonates, pamidronate and, more importantly zoledronic acid may cause
      hypocalcemia, but mostly asymptomatic, mild, transient in most cases. Sufficient
      calcium and vitamin D intake needs to be ensured in patients with malignancy who
      have borderline or low levels of calcium when commencing treatment with
      bisphosphonates. Vitamin D itself induce the formation of osteoclasts by
      increasing the expression of RANKL on marrow stromal cells. Local calcium also
      promotes tumor growth and the production of parathyroid hormone-related peptide
      which in turn stimulates bone resorption. Vitamin D and calcium supplementation
      during bisphosphonate administration for the purpose of elimination of the side
      effects related to hypocalcemia in patients with bone metastasis may increase the
      bone resorption and decrease the efficacy of bisphosphonates. Therefore, vitamin
      D and calcium supplementation must not be routinely recommended during
      bisphosphonate administration.

PMID- 15504570
TI  - Can ataxin-2 be down-regulated by allele-specific de novo DNA methylation in SCA2
      patients?
AB  - Spinocerebellar ataxia type 2 (SCA2) is caused by a CAG trinucleotide repeat
      expansion within the coding region of the ataxin-2 gene. Affected individuals
      typically have between 34 and 57 CAG repeats. Signs of the disorder generally
      begin in adulthood and include progressive ataxia, dysarthria, tremor,
      hyporeflexia, and slow saccades. As with other trinucleotide repeat disorders,
      SCA2 exhibits an inverse correlation between the size of the CAG repeat and the
      age at onset of clinically detectable disease, with neonatal cases of SCA2 being
      reported in individuals harboring over 200 CAG repeats. However, a wide range of
      age at onset is typically observed, especially in individuals with < 40 CAG
      repeats. CAG repeat number alone explains approximately 25-80% of the
      variability. In this paper, we hypothesize that the level of mutant ataxin-2
      protein in affected cells contributes to these differences. One of the mechanisms
      that might influence this protein levels is de novo DNA methylation, which would
      specifically target the allele with the expanded CAG repeat leading to
      transcriptional silencing. Consequently, the symptoms of SCA2 would occur later
      in the patient's life history. Our postulations, as well as those previously
      reported to account for the phenotype of SCA2, are discussed.

PMID- 15504571
TI  - In vitro biosynthesis of plasma proteins under ischemic conditions of closed
      circuit perfusion of healthy and intoxicated rabbit liver.
AB  - We are elaborating on the kinetics and mechanisms of septic rabbit liver to de
      novo biosynthesize acute-phase response (APR) proteins under in vitro conditions
      of deepening ischemia in reference to their in vivo prevalence in serum and
      cerebrospinal fluids (CSF) collected at predetermined times. The significance of
      the data is interpreted as relevant to grafting cadaveric liver into end-stage
      liver diseased patients and APR-induced ischemic heart diseases (IHD). Hepatic
      APR was induced by CCl(4)-intubation, and the administration of cholera toxin
      (CT) or scorpion venom (SV), or both, to rabbits. Hepatic functional efficiency,
      in terms of biosynthesis of APR proteins in closed circuit perfusion of the
      isolated intoxicated liver with oxygenated saline or L-15 media paralleled the
      two-dimensional immunoelectrophoresis (2D-IEP) spectrum of APR serum proteins at
      time of liver isolation. We are suggesting: (a) in vitro biosynthesis of plasma
      proteins by isolated perfused liver is the result of in vivo decoded and retained
      APR inflammatory signals; and (b) decoded inflammatory signals are expressed not
      withstanding the perfusate's organic composition. Furthermore, 90 min of ischemic
      perfusion in saline or L-15 medium precipitated mitochondrial aberrations which
      resulted in further deterioration of de novo biosynthesis of APR plasma proteins.
      Regardless of the nature of the inflammatory stimuli, mitochondrial aberrations
      rendered the perfused organ a biologically inert tissue mass that was incapable
      of resuming biological function upon perfusion with oxygenated L-15 medium. This
      is most likely due to ischemia-induced irreversible hepatic necrosis. Thus, in
      vitro aberrations of mitochondrial function(s) critically limit the capability of
      the isolated liver to resume its organic function to sustain biosynthesis of de
      novo plasma proteins. Extrapolation of these results to the surgical management
      of end-stage liver diseases points to the importance of the status and the
      handling protocol(s) of the cadaver donor liver prior to successful grafting. We
      conclude that although histology of a cadaver liver may reveal well-preserved
      hepatic cellular organelles with at least minimal intra- and intercellular
      communication required for viable hepatic function, we deem it essential to
      further define acceptable minimal capabilities to de novo biosynthesize plasma
      proteins by a cadaver liver as a measure of its functional viability and
      suitability for transplantation. Ultimately, this measure may improve the success
      of liver transplants with minimal surgical and drug interventions.

PMID- 15504572
TI  - A new model for understanding the role of environmental factors in the origins of
      chronic illness: a case study of type 1 diabetes mellitus.
AB  - There is a need for a new pathophysiological model explaining and linking the
      role of numerous non-genetic factors believed to contribute to origins of many
      chronic physical diseases. This article presents a theoretical model for
      explaining the confusing and often contradictory findings regarding the role of
      environmental influences in type 1 diabetes, a disease that has been widely
      studied, for which clear diagnostic criteria exist, and for which development of
      effective prevention strategies represents significant challenges. The model is
      formulated from the large database of research regarding increasing understanding
      of the interaction between environmental factors, physiology, and autonomic
      regulatory function. Data is integrated from research in the fields of the
      experience-dependent maturation of the nervous system and the neurophysiology of
      traumatic stress to demonstrate how disruptions in early bonding and attachment,
      including adverse events such as traumatic stress, are capable of causing: (1)
      long-term imbalances in autonomic regulatory function and (2) relative dominance
      of sympathetic or parasympathetic activity. The proposed model of autonomic
      dysfunction suggests that ongoing mechanisms promoting high glucose in the
      context of decreasing insulin production in type 1 diabetes represent a state of
      relative sympathetic dominance influenced by environmental factors affecting
      autonomic, immune and endocrine systems during critical period programming. The
      model further identifies a link between the many seemingly unrelated non-genetic
      risk factors, and appears capable of explaining contradictions and enigmas in
      epidemiological and clinical studies regarding non-genetic origins of type 1
      diabetes, including the role of stress, variation in age of onset, and duration
      of the preclinical phase.

PMID- 15504573
TI  - Dopamine receptor downregulation: an alternative strategy for schizophrenia
      treatment.
AB  - Schizophrenia is a common and devastating illness. The cause of schizophrenia is
      still unknown and the simplest formulation of the "Dopamine hypothesis" posits
      that schizophrenia results from dopaminergic hyperactivity. Under the hypothesis
      of dopaminergic hyperactivity in schizophrenia, antipsychotics blocking the
      dopamine D2 receptor (DRD2) and other approaches to reduce dopamine (DA)
      transmission have been used to treat schizophrenia. I propose that dopamine
      receptor (DR) downregulation could be an alternative strategy to compromise
      dopaminergic overactivity implicated in the pathogenesis of schizophrenia.
      Agonist-induced receptor downregulation includes receptor proteolysis, modulation
      of receptor gene transcription and affecting of RNA stability. These processes
      cause a decrease of existing receptors and reduction of receptor synthesis. This
      hypothesis could explain the antipsychotic mechanisms of DA agonists or partial
      agonists, like aripiprazole. It is suggested that the development of agents that
      increase DR downregulation could be an alternative strategy for schizophrenia
      treatment.

PMID- 15504574
TI  - What does pain signify? A hypothesis concerning pain, the immune system and
      unconscious pain experience under general anesthesia.
AB  - In this paper, I present a case-study that initiates a discussion about the
      meaning of pain. The case-study concerns a person who was under deep sedation
      during colonoscopy. The person did not experience pain from a first-person
      perspective, although pain was evident to the medical team from a second-person
      perspective. The divergence of pain perspectives raises an interesting quandary.
      If the body communicates pain while pain consciousness is blocked by the sedation
      procedure, our conclusion should be that the intersubjective aspect of pain
      precedes the "subjective," first-person experience of pain. This conclusion is
      not consistent with the common representational conception of pain that places
      the intrasubjective point of view prior to the intersubjective point of view. The
      solution I offer to this quandary is the quasi-paradoxical idea that pain can be
      experienced unconsciously through the immune system. Following this suggestion, I
      hypothesize that post-traumatic stress disorders following general anesthesia may
      result from this unconscious pain experience. If this idea is scientifically
      grounded, then physicians should: (1) consider ways of blocking the unconscious
      pain experience produced by the immune system without interfering with the immune
      response, and (2) study pain as a complex cognitive and unconscious system by
      drawing an analogy with the immune system, which follows similar logic.

PMID- 15504575
TI  - Up-regulatory impact of boron on vitamin D function -- does it reflect inhibition
      of 24-hydroxylase?
AB  - Nutritional intakes of boron have been shown to lessen the adverse consequences
      of vitamin D deficiency in rodents. Pilot clinical studies suggest that this
      effect may be mediated, in whole or in part, by an increase in serum 25
      hydroxyvitamin D. We propose that, in concentrations achievable with good diets,
      boron suppresses the activity of the microsomal enzyme 24-hydroxylase, chiefly
      responsible for catabolism of this steroid. This inhibition may reflect a direct
      interaction with the enzyme, or perhaps boron's ability to form a covalent
      complex with the product of its activity, 24,25-dihydroxyvitamin D. An up
      regulatory impact of boron on 25-hydroxyvitamin D is potentially beneficial in
      light of the fact that the vitamin D status of many individuals is poor during
      winter months, and traditional supplemental doses of this vitamin are often too
      low to correct this problem. There is growing evidence that good vitamin D status
      -- as reflected by 25-hydroxyvitamin D levels -- may reduce risk for a host of
      prominent disorders; thus, boron may have the ability to potentiate this
      protection. Clinical studies also suggest that nutritional boron can up-regulate
      17beta-estradiol levels in women, including postmenopausal women receiving
      hormone replacement therapy. The catabolism of this hormone is achieved by
      microsomal enzymes catalyzing vicinal hydroxylations -- a description that also
      applies to 24-hydroxylase. This suggests the more general hypothesis that
      nutritional boron can inhibit a range of microsomal enzymes which insert hydroxyl
      groups vicinal to existing hydroxyls in steroids -- including the enzymes which
      catabolize estradiol and 25-hydroxyvitamin D.

PMID- 15504576
TI  - Hypothesis: selective phosphodiesterase-5 inhibition improves outcome in
      preeclampsia.
AB  - The pathogenesis of preeclampsia stems from aberrant changes at the placental
      interface. The trophoblastic endovascular invasion of tonic spiral arteries that
      converts them to passive conduits falters. Uteroplacental insufficiency and
      fetoplacental hypoxemia result. Secondary maternal oxidative stress and an
      excessive inflammatory response to pregnancy generate the clinical syndrome of
      preeclampsia. Current treatment focuses on preventing seizures, controlling
      hypertension, preserving renal function and delivering the baby. We propose that
      the pathophysiological changes induced by preeclampsia in the placenta parallel
      those caused by persistent hypoxemia in the lungs at high altitude or with
      chronic obstructive pulmonary disease. Unrelenting pulmonary hypoxic
      vasoconstriction induces pulmonary hypertension and cor pulmonale. Inhalation of
      nitric oxide and phosphodiesterase-5 inhibitors opposes pulmonary hypoxic
      vasoconstriction, alleviates pulmonary hypertension and improves systemic
      oxygenation. Notably nitric oxide donor therapy also counters hypoxemic
      fetoplacental vasoconstriction, a biological response analogous to pulmonary
      hypoxic vasoconstriction. Fetal oxygenation and nutrition improve. Placental
      upstream resistance to umbilical arterial blood flow decreases. Fetal right
      ventricular impedance falls. Heart failure (cor placentale) is avoided. Emergency
      preterm delivery can be postponed. Other than low dose aspirin and antioxidants
      vitamins C and E no available therapy specifically targets the underlying disease
      profile. We hypothesize that, like nitric oxide donation, pharmacological
      inhibition of placental phosphodiesterase-5 will also protect the fetus but for a
      longer time. Biological availability of guanosine 3'5'-cyclic monophosphate is
      boosted due to slowed hydrolysis. Adenosine 3'5'-cyclic monphosphate levels
      increase in parallel. Cyclic nucleotide accumulation dilates intact tonic spiral
      arteries and counters hypoxemic fetoplacental vasoconstriction. Intervillous and
      intravillous perfusion pick up. Maternal to fetal placental circulatory matching
      improves. Enhanced placental oxygen uptake alleviates hypoxemic fetal stress.
      Appropriate fetal nutrition resumes. Cor placentale and severe intrauterine
      growth restriction are averted. Increased maternal cyclic nucleotide
      concentrations promote systemic vasodilatation so that blood pressures fall.
      Preemption of oxidative stress initiated by "consumptive" oxidation of nitric
      oxide stabilizes the vascular endothelium and corrects coagulopathy. Anti
      inflammatory and immunosuppressant adenosine 3'5'-cyclic monphosphate offsets the
      extreme gestational inflammatory response. Cellular injury and multi-organ damage
      are prevented. One tablet a day of the new long acting phosphodiesterase-5
      inhibitor, tadalafil (half life of 17.5 h) theoretically should allow a preterm
      pregnancy affected by preeclampsia to continue safely. Selective monitoring of
      vital organ functions guards against life-threatening maternal complications.
      Regular biophysical profiling warns the obstetrician of impending fetal
      compromise. Fetal growth and vital organ maturation can continue. As a result
      workloads imposed upon neonatal intensivists will lighten. Parental anxiety and
      concern will be allayed. The cost of treating preeclamptic mothers and their
      extremely low birth weight infants will decrease. Money saved by midwifery
      services in poorer states can be used to pay for better prenatal care. Severe
      preeclampsia/eclampsia will be less common. Maternal and perinatal morbidity and
      mortality will be reduced. Because the human immunodeficiency virus often infects
      individuals at a workforce eligible age, the global acquired immunodeficiency
      syndrome pandemic has already brought many nations to the brink of economic ruin.
      Potentially productive lives saved for the future will help restore them
      fiscally.

PMID- 15504577
TI  - An elevation of triglycerides reflecting decreased triglyceride clearance may not
      be pathogenic -- relevance to high-carbohydrate diets.
AB  - The fact that carbohydrate-rich diets often increase plasma triglycerides has led
      some to question the wisdom of such diets. This increase is primarily
      attributable to a decrease in the efficiency of triglyceride clearance -- whereas
      the elevation of triglycerides observed in insulin-resistant subjects stems
      mainly from increased hepatic production of VLDL particles. There is growing
      reason to suspect that the increased coronary risk associated with elevated
      triglycerides in Western epidemiology reflects the fact that high triglycerides
      are a marker for insulin resistance syndrome, rather than any inherent pathogenic
      role of triglycerides per se. Thus, endothelial dysfunction is seen only in those
      hypertriglyceridemic subjects who are insulin resistant, and is absent in
      patients whose markedly elevated triglycerides reflect genetically defective
      lipoprotein lipase activity. Triglyceride levels are relatively high in certain
      Third World societies which are virtually immune to coronary disease so long as
      they persist in their traditional very-low-fat diets; in Ornish's celebrated
      study, a moderate rise in triglycerides coincided with a marked reduction in
      coronary events. Although the particle size of both LDL and HDL tends to decrease
      when triglyceride levels are high, it is questionable whether this effect has a
      major pathogenic impact. The one clear drawback of high-carbohydrate diets is a
      decrease in HDL particle number, resulting from decreased hepatic production of
      apoA-I; this effect is seen whether or not triglycerides increase. The very
      favorable effects of very-low-fat, whole food, quasi-vegan diets on LDL
      cholesterol, insulin sensitivity, and body weight appear to more than compensate
      for this decrease in HDL; it is notable that HDL levels tend to be quite low in
      Third World cultures at minimal risk for coronary disease. On the other hand,
      this decrease in HDL may be of more significance in the context of omnivore diets
      only moderately low in fat, as suggested by the fact that diets higher in
      unsaturated fats emerge as more protective in Western prospective epidemiology.
      The tendency of high-carbohydrate diets to boost triglycerides can be minimized
      by exercise training, supplemental fish oil, an emphasis on fiber-rich, low
      glycemic-index whole foods, and the "spontaneous" weight loss often seen with ad
      libitum consumption of such diets -- measures which are highly recommendable
      whether or not triglycerides are a concern.

PMID- 15504578
TI  - The chronosense -- what light tells man about biological time.
AB  - In the past 10 years, experimental studies have provided further evidence for the
      suggestion that the eye serves man as a dual sense organ, viz as a sense organ
      for sight but also for time and the regulation of biological rhythms. A small
      group of scientists interested in the adjustment of biological rhythms to the key
      Zeitgeber light wanted to answer the question whether rods and/or cones and/or
      other uncharacterized retinal photoreceptors contribute to this function in
      mammals. Intriguingly, in the course of elegant research, a number of
      laboratories around the world have been zeroing in on a novel non-rod, non-cone
      ocular photopigment which serves a number of responses to non-image-forming (NIF)
      photoreception in mammals. This paper intends to draw attention to possible
      implications of photoreception and phototransduction research for other
      scientific disciplines which study health and diesase effects in man. We
      therefore review the pivotal role of the photoreceptors -- old and new -- for the
      light-related timing and coordination of the interplay of otherwise less
      efficient biological rhythms. To distinguish our focus on time- and timing
      related effects from classic image-forming (IF) and other NIF responses to
      ambient light, we refer informatively to chronoreceptors which mediate the sense
      of time, or chronosense. We conclude that syndisciplinary research into the
      physiology and pathophysiological implications of the chronosense is warranted
      and summarize a series of research questions.

PMID- 15504579
TI  - Prenatal alcohol exposure, circadian rhythm, and serotonin.

PMID- 15504580
TI  - Molecular basis of purinergic signaling in neutrophil activation and
      degranulation: a current perspective.

PMID- 15504581
TI  - Possible alternative treatments of Alzheimer's disease.

PMID- 15504582
TI  - Immunomodulation, allohormones and fertility.

PMID- 15504583
TI  - Hypotension associated with autonomic dysfunction: a possible cause of vertigo?

PMID- 15504584
TI  - The transmission of phocine herpesvirus-1 in rehabilitating and free-ranging
      Pacific harbor seals (Phoca vitulina) in California.
AB  - Phocine herpesvirus-1 (PhHV-1) causes regular outbreaks of disease in neonatal
      harbor seals (Phoca vitulina) at rehabilitation centers in Europe and in the U.S.
      To investigate transmission of this virus samples were collected from harbor seal
      pups during exposure studies at a Californian rehabilitation center from 1999 to
      2002 and from free-ranging harbor seals off central California during the same
      period. The exposure studies provided evidence that PhHV-1 can be transmitted
      horizontally between animals most likely through direct contact with oro-nasal
      secretions. However vertical transmission may also occur, as adult female harbor
      seals were found to be shedding the virus in vaginal and nasal secretions, and
      premature newborn pups had evidence of early infection. Results also indicated
      that PhHV-1 infections were common in both free-ranging (40%, 49/121) and
      rehabilitating (54%, 46/85) young harbor seals, during the spring and early
      summer. This timing, which correlated with pupping and weaning, suggested that
      the majority of animals were infected and infective with PhHV-1 between pupping
      and breeding.

PMID- 15504585
TI  - Procedures for preventing transmission of foot-and-mouth disease virus (O/TAW/97)
      by people.
AB  - The aim of this study was to determine personal hygiene protocols and animal
      avoidance periods needed to prevent transmission of FMDV (O/TAW/97). Forty-six, 9
      week-old barrows free of FMDV were randomly allocated to five treatment groups
      and a control group. Investigators contacted and sampled FMDV-inoculated pigs for
      approximately 40 min and then contacted and sampled sentinel pigs after using no
      biosecurity procedures, washing hands and donning clean outerwear, or showering
      and donning clean outerwear. Personnel were sampled for nasal carriage of FMDV
      for 85.43 h. Contaminated personnel did not transmit FMDV to susceptible pigs
      after handwashing or showering, and donning clean outerwear. FMDV was transmitted
      when biosecurity procedures were not used. FMDV was not detected in nasal
      secretions of investigators. Thus, extended animal avoidance periods do not
      appear to be necessary to prevent transmission of FMDV (O/TAW/97) by people to
      pigs when organic material is removed through handwashing/showering and donning
      clean outerwear. This study supports similar findings in a previous publication
      using FMDV (O/UK/35/2001).

PMID- 15504586
TI  - Detection of carriers of foot-and-mouth disease virus among vaccinated cattle.
AB  - To investigate and optimise detection of carriers, we vaccinated 15 calves with
      an inactivated vaccine based on foot-and-mouth disease virus (FMDV) A Turkey
      strain and challenged them and two further non-vaccinated calves with the
      homologous virus four weeks later. To determine transmission to a sensitive
      animal, we put a sentinel calf among the infected cattle from 60 days post
      infection until the end of the experiment at 609 days post-infection. Samples
      were tested for the presence of FMDV, viral genome, specific IgA antibodies,
      antibodies against FMDV non-structural (NS) proteins or neutralising antibodies.
      Virus and viral genome was intermittently isolated from probang samples and the
      number of isolations decreased over time. During the first 100 days significantly
      more samples were positive by RT-PCR than by virus isolation (VI), whereas, late
      after infection more samples were positive by virus isolation. All the inoculated
      cattle developed high titres of neutralising antibodies that remained high during
      the entire experiment. An IgA antibody response was intermittently detected in
      the oropharyngeal fluid of 14 of the 17 calves, while all of them developed
      detectable levels of antibodies to NS proteins of FMDV in serum, which declined
      slowly beyond 34 days post-infection. Nevertheless, at 609 days after
      inoculation, 10 cattle (60%) were still positive by NS ELISA. Of the 17 cattle in
      our experiment, 16 became carriers. Despite frequent reallocation between a
      different pair of infected cattle no transmission to the sentinel calf occurred.
      It remained negative in all assays during the entire experiment. The results of
      this experiment show that the NS ELISA is currently the most sensitive method to
      detect carriers in a vaccinated cattle population.

PMID- 15504587
TI  - Wild rabies virus detection by plaque assay from naturally infected brains in
      different species.
AB  - A simple, sensitive and specific plaque assay protocol for the detection of wild
      type rabies virus in different species is described using confluent monolayers of
      chicken embryo cells in 6-well plates. Plaques are produced after application of
      either agarose or Sephadex G-100 overlay onto cell monolayers and incubation for
      96 h after virus infection at 37 degrees C. The parameters affecting plaque
      appearance include cell seeding concentration, overlay composition and time of
      incubation after infection. Optimal conditions are seeding at a concentration of
      4 x 10(6) cell/cm(3), incubation at 37 degrees C in 5% CO(2) atmosphere during 96
      h, using either 1% agarose or 2% Sephadex G-100 overlays. The described plaque
      assay would be a new valuable tool in conducting various quantitative
      investigations, since the chicken embryo cells are susceptible to rabies virus
      infection from all species studied.

PMID- 15504588
TI  - Co-circulation of two genetically distinct viruses in an outbreak of African
      swine fever in Mozambique: no evidence for individual co-infection.
AB  - In 1998, domestic pigs originating from villages within a 40 km radius of Ulongwe
      in the northern Tete Province of Mozambique were held in a quarantine facility
      for a 3-month period prior to their importation into South Africa. Eight of a
      total of 25 pigs died within the first 3 weeks of quarantine of what appeared
      clinically and on post mortem examination to be African swine fever (ASF). Organs
      were collected and preserved in formol-glycerosaline and the presence of ASF
      virus in these specimens was confirmed by three independent polymerase chain
      reaction (PCR) tests. Two gene regions were characterised, namely the C-terminus
      end of the major immunodominant protein VP72 and the central variable region
      (CVR) of the 9RL open reading frame (ORF). Results confirmed the presence of two
      genetically distinct viruses circulating simultaneously within a single outbreak
      focus. However, despite the pigs being housed within the same facility, no
      evidence of co-infection was observed within individual animals. Comparison of
      the two 1998 virus variants with viruses causing historical outbreaks of the
      disease in Mozambique revealed that these viruses belong to two distinct
      genotypes which are unrelated to viruses causing outbreaks between 1960 and 1994.
      In addition, the CVR and p72 gene regions of one of the 1998 Mozambique virus
      variants (variant-40) was shown to be identical to the virus recovered from an
      ASF outbreak in Madagascar in the same year, whilst the other (variant-92) was
      identical to a 1988 pig isolate from Zambia.

PMID- 15504589
TI  - Ehrlichia ruminantium seroprevalence in domestic ruminants in Ghana. II. Point
      prevalence survey.
AB  - Serum samples collected on a single occasion from cattle, sheep and goats at
      sites in all 10 regions of Ghana were tested for antibodies to Ehrlichia
      (previously Cowdria) ruminantium, the causative agent of heartwater, by
      polyclonal competitive ELISA (PC-ELISA). The survey revealed the presence of
      heartwater-exposed ruminants throughout the country, with local seroprevalence up
      to 100%. Seronegative, and therefore presumably susceptible, animals were also
      present in all regions, in some areas in numbers high enough to indicate local
      endemic instability. Overall seroprevalences in cattle, sheep and goats were 61,
      51 and 28% respectively, and were generally higher in the northern part of the
      country and lower in the forest zone. Amongst animals over 1 year old, two thirds
      of cattle and sheep, and around one third of goats throughout the country had
      been exposed to E. ruminantium. In the north, seroprevalence in sheep sampled
      with and without cattle was similar, whereas in the south seroconversion rates in
      sheep were significantly higher in areas where cattle were present.

PMID- 15504590
TI  - Oxytetracycline as a predisposing condition for chalkbrood in honeybee.
AB  - Antibiotics, particularly oxytetracycline, have been discussed as a possible
      predisposing condition in the appearance of chalkbrood in the honeybee (Apis
      mellifera L.). Nevertheless, the scientific data to support this belief have been
      insufficient. We have developed a method to study the effects of this antibiotic
      as a predisposing factor under different circumstances. We conclude that
      oxytetracycline does not increase the risk of chalkbrood in susceptible worker
      brood in the short or mid-term.

PMID- 15504591
TI  - An experimental mouse model of progressive atrophic rhinitis of swine.
AB  - Pasteurella multocida is responsible for a variety of diseases of veterinary
      importance, including the pig disease progressive atrophic rhinitis (PAR). The
      feasibility of using the mouse as an experimental model of PAR was evaluated. We
      experimentally infected the upper respiratory tract of immature mice with a pig
      isolate of P. multocida that produces the toxin responsible for causing the nasal
      lesions characteristic of PAR. We tracked the health status and weight gain of
      these mice for one month following infection, after which the mice were killed
      and the integrity of the nasal turbinates was examined. Mice infected with P.
      multocida appeared healthy throughout the study, although the growth rate of
      these mice was reduced significantly compared with non-infected control animals.
      Infected animals also demonstrated marked nasal atrophy analogous to that seen in
      naturally occurring PAR of swine, with shortening and thinning of the turbinate
      scrolls and inflammatory cell involvement. The mouse therefore provides a
      convenient model for the further investigation of PAR of swine.

PMID- 15504592
TI  - Distribution of Mycobacterium avium subsp. paratuberculosis in organs of
      naturally infected bull-calves and breeding bulls.
AB  - Paratuberculosis, caused by Mycobacterium avium subsp. paratuberculosis, has
      particular importance in cattle due to the resulting chronic diarrhoea, weight
      loss, decreased production, infertility and eventual death. While faecal oral
      route of infection is generally recognised, reports about semen-derived infection
      are rare. The objective of this work was to assess whether M.a. paratuberculosis
      may disseminate from the gastrointestinal tract to reproductive organs, and
      compare this event between naturally infected bull-calves and breeding bulls. Ten
      bull-calves, aged 6-28 weeks and four breeding bulls were tested by serology,
      faecal and tissue culture, IS900 PCR and RFLP. In seven bull-calves M.a.
      paratuberculosis was isolated predominantly from mesenteric lymph nodes (75%);
      isolates from mucosa of the intestine constituted 25%. In three breeding bulls,
      M.a. paratuberculosis was isolated both from intestinal mucosa and mesenteric
      lymph nodes. Head and mediastinal lymph nodes, liver, spleen and semen of bull
      no. 1 (Holstein-Friesian); testes and epididymis of bull no. 2 (Piemonte);
      testes, epididymides and seminal vesicle of bull No. 3 (Hereford); and seminal
      vesicle of bull No. 4 (Simmental) tested positive by culture. Hot-start PCR
      revealed M.a. paratuberculosis in semen, seminal vesicle and intestinal tissue
      where culture isolation was difficult. Isolates from bull-calves and breeding
      bulls were of RFLP types B-C9 and B-C1, respectively. Bull-calves born in
      infected herd can be sources of infection when later used for natural mating or
      artificial insemination. Sub-clinically infected bulls release M.a.
      paratuberculosis into semen, consequently infecting the uterine environment of
      cows.

PMID- 15504593
TI  - The effect of mutation on Rhodococcus equi virulence plasmid gene expression and
      mouse virulence.
AB  - An 81 kb virulence plasmid containing a pathogenicity island (PI) plays a crucial
      role in the pathogenesis of Rhodococcus equi pneumonia in foals but its specific
      function in virulence and regulation of plasmid-encoded virulence genes is
      unclear. Using a LacZ selection marker developed for R. equi in this study, in
      combination with an apramycin resistance gene, an efficient two-stage homologous
      recombination targeted gene mutation procedure was used to mutate three virulence
      plasmid genes, a LysR regulatory gene homologue (ORF4), a ResD-like two-component
      response regulator homologue (ORF8), and a gene (ORF10) of unknown function that
      is highly expressed by R. equi inside macrophages, as well as the chromosomal
      gene operon, phoPR. Virulence testing by liver clearance after intravenous
      injection in mice showed that the ORF4 and ORF8 mutants were fully attenuated,
      that the phoPR mutant was hypervirulent, and that virulence of the ORF10 mutant
      remained unchanged. A virulence plasmid DNA microarray was used to compare the
      plasmid gene expression profile of each of the four gene-targeted mutants against
      the parental R. equi strain. Changes were limited to PI genes and gene induction
      was observed for all mutants, suggesting that expression of virulence plasmid
      genes is dominated by a negative regulatory network. The finding of attenuation
      of ORF4 and ORF8 mutants despite enhanced transcription of vapA suggests that
      factors other than VapA are important for full expression of virulence. ORF1, a
      putative Lsr antigen gene, was strongly and similarly induced in all mutants,
      implying a common regulatory pathway affecting this gene for all four mutated
      genes. ORF8 is apparently the centre of this common pathway. Two distinct highly
      correlated gene induction patterns were observed, that of the ORF4 and ORF8
      mutants, and that of the ORF10 and phoPR mutants. The gene induction pattern
      distinguishing these two groups paralleled their virulence in mice.

PMID- 15504595
TI  - Genotypic and phenotypic screening of high and low virulence Staphylococcus
      aureus isolates from rabbits for biofilm formation and MSCRAMMs.
AB  - At rabbit flock level, two types of Staphylococcus aureus infections can be
      distinguished. In the first type, caused by low virulence strains, the infection
      remains limited to a small number of animals. The second type of infection is
      caused by the high virulence strains, which spread throughout the rabbitry. The
      pathogenetic capacity of a particular S. aureus strain is attributed to a
      combination of extracellular factors and invasive properties such as adherence
      and biofilm formation. Twenty eight high virulence and 34 low virulence S. aureus
      isolates recovered from rabbits between 1998 and 2003 were used to study slime
      production on Congo red Agar (CRA) and prevalence of bap, icaA and icaD
      associated with biofilm formation. Furthermore these strains were screened for
      the presence of bbp, clfA, clfB, cna, ebpS, eno, fnbA, fnbB and fib encoding
      microbial surface components recognizing adhesive matrix molecules (MSCRAMMs).
      The presence of icaA and icaD was not correlated with slime production on CRA.
      Bap was absent in all strains. All rabbit S. aureus strains harboured clfA and
      clfB. The prevalences of ebpS, eno, fnbA and fib did not reveal striking
      differences between high and low virulence strains. FnbB prevalence in high
      virulence isolates was lower than in low virulence isolates and cna was absent in
      high virulence strains. It was remarkable that only high virulence strains were
      positive for bbp. Further research is necessary to elucidate the significance of
      bbp in the pathogenesis of high virulence strains.

PMID- 15504594
TI  - Molecular characterisation and ovine live vaccine 1B evaluation toward a
      Chlamydophila abortus strain isolated from springbok antelope abortion.
AB  - Chlamydiosis is a zoonosis with a worldwide distribution. The reservoir of
      susceptible hosts is large and includes birds and both domestic and wild mammals.
      Chlamydial infection, determined serologically, seems to be widespread among wild
      ruminants in the Paris zoo (France). In February 2003, an abortion case was
      reported within the springbok (Antidorcas marsupialis) herd of the zoo. PCR assay
      using primers targeting the polymorph membrane protein gene (pmp) family was
      performed on both vaginal swab and placenta samples revealing the presence of
      Chlamydophila. The inoculation into chicken embryos of an infected placenta
      extract led to the successful isolation of a C. abortus strain referred to as
      ASb1. The omp1 gene coding the major outer membrane protein (momp) and the 16S
      23S rRNA spacer region of ASb1 were compared to those of various strains by
      restriction fragment length polymorphism (RFLP). The RFLP analysis showed that
      this isolate belonged to Chlamydophila abortus species and is highly related to
      known domestic ruminant's strains causing abortion. The efficacy of a live
      vaccine 1B, based on a temperature-sensitive mutant of the ovine abortion
      reference strain AB7, was tested. Protection-challenge experiments in a mouse
      model show that the ASb1 strain led to mice abortions and that vaccination with
      1B vaccine provided them with effective protection.

PMID- 15504596
TI  - First isolation of Mycobacterium microti (Llama-type) from a dog.
AB  - We report the first isolation of Mycobacterium microti from a dog with lesions of
      acute peritonitis. The isolate was demonstrated to be M. microti of Llama-Type by
      spoligotyping. Epidemiological implications of the isolation of this possibly
      zoonotic agent from a dog are discussed.

PMID- 15504597
TI  - Serological characterization of Danish Haemophilus parasuis isolates.
AB  - A total of 103 Danish Haemophilus parasuis field isolates was collected from
      diseased pigs in connection with routine diagnostics. The isolates were serotyped
      using indirect haemagglutination (IHA) and for 57 of the isolates the serotyping
      was also performed by immunodiffusion. Serovar 5 was the most prevalent (36%),
      followed by serovar 4 (13%) and serovar 13 (22%), whereas 15% of the strains were
      nontypeable by IHA. Serovars 1, 2, 6, 7, 9, 12, 14, and 15 were only represented
      by a small number of isolates. Most of the Danish isolates belong to serovars,
      which earlier have been shown to be virulent. The strains could be divided into
      two groups depending on whether they were isolated from cases with systemic
      disease (polyserositis, arthritis or meningitis) or if they only were found in
      the lower respiratory tract. The most marked differences were observed for
      serovar 4, which had a higher prevalence in respiratory disease compared to
      systemic infection, and for the nontypeable isolates, which were mainly found in
      cases of systemic infection.

PMID- 15504598
TI  - The guide to plotting a cochleogram.
AB  - The cochleogram is commonly used for illustrating hair cell loss after insult,
      yet standardized procedures for plotting either individual or averaged
      cochleograms are lacking despite more than 40 years of use. Due to the intra
      species variation in basilar membrane (BM) length, it is important that length is
      plotted on the cochleogram in percent and not millimeter. It is also of interest
      to correlate the location of lesion to frequency by using a frequency-place
      equation. However, there is no consensus as which equation is most suitable for
      the species under study. This is an important issue since two different equations
      can result in significantly different frequency-place maps for the same cochlea.
      The purpose of this presentation is to suggest procedures for standardizing the
      cochleogram. The guidelines include: (i) basilar membrane length should be
      plotted as percent instead of millimeter due to the biological variation that
      exists in BM length within a particular species and strain, and the total length
      in millimeter stated on the cochleogram; (ii) the equations used for frequency
      place maps should be stated on the cochleogram; (iii) different basilar membrane
      lengths should be normalized to percent before averaged cochleograms are made.
      These procedures are illustrated and discussed.

PMID- 15504599
TI  - Minocycline attenuates gentamicin induced hair cell loss in neonatal cochlear
      cultures.
AB  - Minocycline, a second-generation tetracycline antibiotic used against gram
      negative and gram-positive bacteria, protects against a wide range of
      neurodegenerative disorders by inhibiting caspases, iNOS and the release of
      cytochrome c. Since aminoglycoside antibiotics damage sensory hair cells in the
      inner ear by activating caspase-mediated cell death pathways, we hypothesized
      that minocycline would protect against gentamicin (GM) ototoxicity. To test this
      hypothesis, postnatal day 3 (P3) rat, cochlear organotypic cultures were treated
      with GM alone or in combination with minocycline (10-500 microM). Treatment with
      GM induced a dose-dependent loss of outer hair cells (OHC) and inner hair cells
      (IHC). Addition of minocycline to the GM-treated cultures greatly reduced the
      amount of GM-induced hair cell damage in P3 cochlear cultures. The greatest
      protection was achieved with 100 microM of minocycline. Application of
      minocycline alone had no adverse effects on hair cell survival. The advantage of
      this combination therapy is that minocycline prevents GM-induced hair cell loss
      while helping to suppress the bacterial infection.

PMID- 15504600
TI  - GJB2 gene mutations in newborns with non-syndromic hearing impairment in Northern
      China.
AB  - Mutations in GJB2 account for the majority of recessive forms of prelingual
      hearing loss. However, in most previous studies it was not possible to
      distinguish between congenital (present at birth) and non-congenital prelingual
      hearing loss. In the present study, the frequency of GJB2 alleles in 20 newborns
      with bilateral severe-to-profound non-syndromic hearing impairment (NSHI) who
      were found at birth through newborn hearing screening and clinical examination is
      reported. PCR was used to amplify the coding region of GJB2 gene followed by
      sequencing analyses. Fifty volunteers with normal hearing were included as
      controls. Results showed that three cases were 235delC/235delC homozygotes; one
      was 235delC/605ins46 compound heterozygotes, 605ins46 mutation was a novel
      mutation reported in the Chinese population; another was 235delC/299-300delAT
      compound heterozygotes. 25% (5/20) of the deafness in newborns studied was caused
      by GJB2 gene mutations. The frequency of 235delC allele carrier in patients and
      in control group was 22.5% and 1%, respectively. One case was identified as being
      a 235delC heterozygote without other mutations detected. Besides, multiple
      polymorphisms such as V27I, V37I, E114G, T123N were also detected. In conclusion,
      GJB2 analysis is an important test that identifies a major cause of newborns with
      bilateral severe-to-profound NSHI screened by universal newborn hearing screening
      in Northern China. The most common pathologic mutation of GJB2 in studied cases
      was 235delC. Molecular analysis and genetic counseling will be extremely
      important for congenital deafness present at birth.

PMID- 15504601
TI  - On generation of statoconia in gravireceptors of mollusks.
AB  - Two models of development of statoconia in the statocyst of mollusks, based on
      the experimental data [Hearing Res. 49 (1990) 63; Hearing Res. 109 (1997) 125;
      Hearing Res. 109 (1997) 109;] are proposed. The purpose of the present work is to
      apply mathematical modeling to the analysis of mechanisms of statoconia formation
      and generation by supporting cells at the stage of their accumulation in the cyst
      lumen. In the case of Aplysia californica, it is not clear whether there is a
      temporal change of statoconia due to their growth in the cyst lumen similar to
      that in Biomphalaria, or whether the growth of statoconia occurs in supporting
      cells before they get into the cyst lumen. This question has to do with a more
      general and insufficiently investigated problem of the mechanisms of statoconia
      evolution during their stage of accumulation. This is related to A. californica
      as well as to the initial phase of development of Biomphalaria glabrata. This
      problem is of practical importance because the majority of experiments related to
      the study of the effects of altered gravity on the development of gravireceptors
      in the two mollusks A. californica and B. glabrata deals with the initial phase
      of statoconia development. It is assumed that two main processes determine the
      evolution of statoconia in developing mollusks: generation of new statoconia by
      growing supporting cells and growth of statoconia sizes in the cyst lumen.
      Analysis of experimental data related to the generation of statoconia in Aplysia
      and comparison of these data with the results of modeling of accumulation of
      statoconia suggest that the basic mechanism of evolution of size distribution of
      statoconia in Aplysia is growth of embryonic statoconia in supporting cells, that
      follows the growth of animal size. Thus, the large sizes of statoconia are
      determined by their development within supporting cells rather than by their
      growth in the cyst lumen. Analysis of the data concerning Biomphalaria allows us
      to assume that distribution of supporting cells which generate statoconia also
      varies. The results of modeling of evolution of statoconia specify necessary
      additional experiments, which are required to refine and test the model.

PMID- 15504602
TI  - Analysis of differential gene expression in the cochlea and kidney of mouse by
      cDNA microarrays.
AB  - Microarray hybridization analysis of gene expression in the cochlea and kidney
      suggest a relationship between these tissues at the genomic level, indicating the
      common gene expression, likely serving a common function in both the organs
      primarily maintaining ion transport, and implied previously from morphological,
      pharmaco-kinetic and teratogenic studies. The cDNAs of more than 100 genes listed
      on the hereditary hearing loss homepage were amplified as targets by RT-PCR and
      were hybridized with probes prepared from total RNA of the cochlea and the
      kidney. Thirteen of the genes analyzed showed altered fluorescence ratios of more
      than two logs. Of these, the expressions of 11 genes were over expressed and two
      were under expressed in the cochlea than in the kidney. Our data is the first
      report to corroborate the genomic similarities between these two important organs
      and may help to explain the somewhat similar response of these organs to certain
      therapeutic drugs.

PMID- 15504603
TI  - Time sequence of degeneration pattern in the guinea pig cochlea during cisplatin
      administration. A quantitative histological study.
AB  - We investigated the key tissues that are implicated in cisplatin ototoxicity
      within the time window during which degeneration starts. Guinea pigs were treated
      with cisplatin at a dose of 2 mg/kg/day for either 4, 6, or 8 consecutive days.
      Histological changes in the organ of Corti, the stria vascularis and the spiral
      ganglion were quantified at the light microscopical level. Outer hair cell (OHC)
      loss started between 4 and 6 days of cisplatin administration, but is only
      significantly different from the non-treated group after 8 days of treatment.
      Midmodiolar OHC counts were comparable to the cytocochleogram data. The cross
      sectional area of the stria vascularis did not differ from the non-treated group,
      nor did an endolymphatic hydrops develop during the course of treatment. Spiral
      ganglion cell (SGC) densities did not decrease. After 6 days, however, detachment
      of the myelin sheath of the type-I SGCs was seen in the lower basal turn, whereas
      after 8 days it was also present in the more apically located turns. Myelin
      sheath detachment is the result of perikaryal shrinkage and swelling of the
      myelin sheath. The present study confirms that cisplatin at a daily dose of 2
      mg/kg has a detrimental effect on the OHCs as well as on the type-I SGCs. These
      intracochlear effects occur simultaneously; OHC loss and SGC shrinkage start
      between the fourth and sixth day of cisplatin administration and appear to
      develop in parallel. At this dose, no histological effect on the stria vascularis
      could be observed, although previous electrophysiological experiments
      demonstrated a clear effect on the endocochlear potential

PMID- 15504604
TI  - Effect of stimulus frequency and stimulation site on the N1m response of the
      human auditory cortex.
AB  - The aim of the present study was to investigate the functional organization of
      the auditory cortex for pure tones of 1, 2, 4, 6, 8 and 12 kHz. Ten subjects were
      tested with a whole-head magnetometer (151 channels). The location, latency and
      amplitude of the generators of the N1m (the main component of the response,
      peaking approximately at 100 ms) were explored simultaneously in the right and
      left hemispheres under monaural stimulation. Our results revealed that tonotopy
      is a rather complex functional organization of the auditory cortex. From 1 to 12
      kHz, tonotopic maps were found for contralateral as well as for ipsilateral
      stimulation: N1m generators were found to be tonotopically organized mainly in an
      anterior-posterior direction in both hemispheres, whatever the stimulated ear,
      but also in an inferior-superior direction in the right hemisphere. Furthermore,
      latencies were longer in the left than in the right hemisphere. Two different
      representations of spectral distribution were found in the right auditory cortex:
      one for ipsilateral and one for contralateral stimulation.

PMID- 15504605
TI  - Localization of prostanoid receptors and cyclo-oxygenase enzymes in guinea pig
      and human cochlea.
AB  - Endogenous production of prostaglandins has been demonstrated in the cochlea, but
      no information is available on the distribution of the cyclo-oxygenase (COX)
      enzymes, or prostanoid receptors in the cochlea. The purpose of the present study
      was to investigate the localization of the FP, EP(1) and EP(3) prostanoid
      receptors as well as the COX-1 and COX-2 enzymes in the cochlea of guinea pig and
      man. Cochleas were processed for immunohistochemistry using routine techniques.
      Appropriate controls comprised incubation with specific blocking peptides, or
      incubation without primary antibodies. Both in guinea pig and man the FP
      prostanoid receptor was abundantly distributed in the cochlea, e.g., in stria
      vascularis, the spiral ligament, spiral ganglion, and organ of Corti. The
      immunohistochemical staining of the EP(1) and EP(3) receptors in the same
      structures was significantly weaker and sometimes lacking altogether (e.g., EP(3)
      receptor in human cochlea). Weak, but mostly consistent immunostaining of the COX
      1 enzyme was found in the cochlear structures. The COX-2 enzyme appeared to be
      lacking. The abundant distribution of the FP receptor in several important
      cochlear structures both in guinea pig and man suggests a physiological function
      for PGF(2alpha) in the cochlea. The COX-1 enzyme seems to be constitutively
      expressed in the cochlea in contrast to COX-2.

PMID- 15504606
TI  - Directionality of hearing in two CF/FM bats, Pteronotus parnellii and Rhinolophus
      rouxi.
AB  - The head-related transfer function (HRTF) has been measured in two CF/FM bats,
      Pteronotus parnellii and Rhinolophus rouxi from 575 positions in the frontal
      hemisphere. P. parnellii showed an increase of the elevation angle of the axis of
      highest pinna gain with increasing frequency followed by a specific decrease at
      75 kHz. Such a drop of elevation angle of the acoustic axis was not seen in R.
      rouxi. The HRTF further showed a spectral notch dependent on elevation and
      frequency in P. parnellii, but not in R. rouxi. The functional implications of
      this difference between both bat species are discussed. Frequencies at maximum
      pinna gain values did not clearly match the frequencies of the harmonics of the
      echolocation calls whereas spatial resolution of interaural intensity differences
      was best in a frequency range that included the higher harmonics of the
      echolocation calls in both bat species. However, specializations of HRTF patterns
      matching the exact frequencies of the harmonics of the echolocation calls could
      not be observed in both bat species.

PMID- 15504607
TI  - Mandarin tone recognition in cochlear-implant subjects.
AB  - This study examined tone recognition in five cochlear-implant subjects who were
      native speakers of Mandarin and used a Nucleus-22 device. Psychophysical
      experiments were conduced to measure rate discrimination in individual electrodes
      from the most apical to the most basal electrodes. The rate range was from 100 to
      200 Hz, which corresponded to the range of variation in fundamental frequency for
      the tonal tokens used in this study. Speech recognition experiments were also
      conducted to measure tone recognition as function of the number of electrodes
      from a 1-electrode map to a 20-electrode map. Large individual variability was
      observed for both rate discrimination and tone recognition result: Average rate
      discrimination ranged between 0.2 and 1.2 (Weber's fraction) whereas tone
      recognition ranged between 30% and 70% correct. A highly significant correlation
      was found between rate discrimination and tone recognition with the 20-electrode
      map, but a non-significant correlation was observed with the 1-electrode map due
      to a floor effect in tone recognition. The present result supports the hypothesis
      that both spectral and temporal cues contribute to tone recognition. In addition,
      the present result shows that current cochlear-implant subjects produced
      significantly lower performance than acoustic simulations in normal-hearing
      subjects, suggesting that neither temporal nor spectral cues have been adequately
      and appropriately extracted and encoded in current cochlear implants. New designs
      are discussed to improve tone recognition in cochlear implant subjects.

PMID- 15504608
TI  - Computational models of hair cell bundle mechanics: I. Single stereocilium.
AB  - A distributed parameter model for describing the response of a stereocilium to an
      applied force is presented. This model is based on elasticity theory, plus the
      geometry and material properties of the stereocilium. The stereocilia shaft above
      the taper is not assumed to be perfectly rigid. It is assumed to be deformable
      and that two separate mechanisms are involved in its deformation: bending and
      shear. The influence of each mode of deformation is explored in parametric
      studies. Results show that the magnitude of tip deflection depends on the shear
      compliance of the stereocilium material, the degree of base taper, and
      stereocilium height. Furthermore, the deformation profiles observed
      experimentally will occur only if there are constraints on the geometry and
      material properties of the stereocilium.

PMID- 15504609
TI  - Computational models of hair cell bundle mechanics: II. Simplified bundle models.
AB  - Simplified versions of hair cell bundles are mechanically modeled. The influence
      of various geometric and material combinations on bundle stiffness, link tensions
      and deformation shape are examined. Three models are analyzed within this paper:
      two stereocilia connected by one link, two stereocilia connected by a
      biologically realistic set of links, and a column of stereocilia connected by
      realistic links. Stereocilia are modeled using a distributed parameter model [J.
      Biomech. Eng. 122, 44]. Some fundamental rules for linking bundles emerge from
      these tests: (1) Links must have a threshold stiffness value for the bundle to
      deform as a whole. Beyond this value, the stereocilia are perfectly linked and
      variations in link stiffness do not significantly effect the bundle stiffness or
      link tension. (2) Decreasing the relative heights of successive stereocilia may
      increase link tension while decreasing bundle stiffness. (3) When lateral links
      exist, the top most lateral links carry the majority of tension. Lower links in
      single column model appear mechanically insignificant. (4) Extending the length
      of the bundle in a column does not increase the stiffness once the column reaches
      a certain length.

PMID- 15504610
TI  - Computational models of hair cell bundle mechanics: III. 3-D utricular bundles.
AB  - Six utricular hair bundles from a red-eared turtle are modeled using 3-D finite
      element analysis. The mechanical model includes shear deformable stereocilia,
      realignment of all forces during force load increments, and tip and lateral link
      inter-stereocilia connections. Results show that there are two distinct bundle
      types that can be separated by mechanical bundle stiffness. The more compliant
      group has fewer total stereocilia and short stereocilia relative to kinocilium
      height; these cells are located in the medial and lateral extrastriola. The stiff
      group are located in the striola. They have more stereocilia and long stereocilia
      relative to kinocilia heights. Tip link tensions show parallel behavior in
      peripheral columns of the bundle and serial behavior in central columns when the
      tip link modulus is near or above that of collagen (1x10(9) N/m(2)). This
      analysis shows that lumped parameter models of single stereocilia columns can
      show some aspects of bundle mechanics; however, a distributed, 3-D model is
      needed to explore overall bundle behavior.

PMID- 15504613
TI  - Novel therapies for treating acute agitation.

PMID- 15504611
TI  - Protection of auditory function against noise trauma with local caroverine
      administration in guinea pigs.
AB  - Glutamate is the most likely neurotransmitter at the synapse between the inner
      hair cell and its afferent neuron in the peripheral auditory system. Intense
      noise exposure may result in excessive glutamate release, binding to the post
      synaptic receptors and leading to neuronal degeneration and hearing impairment.
      The present study investigated the protective effect of caroverine, an antagonist
      of two glutamate receptors, N-methyl-D-aspartate and alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid, on noise-induced hearing loss. Two different
      doses of caroverine were applied onto the round window membrane with gelfoam,
      followed by one-third-octave band noise centered at 6.3 kHz (110 dB SPL) for 1 h.
      Auditory brainstem responses were measured at regular time intervals afterwards.
      Caroverine was found to offer significant protection of the cochlear function
      against noise-induced hearing loss.

PMID- 15504614
TI  - Safety of medications used to treat acute agitation.

PMID- 15504615
TI  - Updated treatment algorithm.

PMID- 15504616
TI  - Future directions in research.

PMID- 15504617
TI  - Intramuscular antipsychotics: clinical experience review.
AB  - Acute agitation is a therapeutic dilemma. Rapid control of agitation is necessary
      to minimize danger both to recipients of care and to caregivers. Although a
      comprehensive assessment may ultimately be necessary to determine the cause of
      agitation and to identify or exclude underlying medical illness, it is often
      imperative to treat agitation immediately. In this imperfect clinical world, it
      is essential to have treatments that are both safe and effective for patients
      with a wide variety of causes of agitation.

PMID- 15504618
TI  - Standard therapies for acute agitation.

PMID- 15504619
TI  - Study of unmet needs in symptomatic veterans with advanced cancer: incidence,
      independent predictors and unmet needs outcome model.
AB  - Veteran patients possess distinctive characteristics such as a higher mortality
      rate, lower socioeconomic status and poorer health status. We report the
      prevalence and predictors of unmet needs and examine the association between
      unmet needs and quality of life (QOL). Two hundred ninety-six male cancer
      patients who presented with distressing symptom(s) completed the following
      instruments: a 14-item multidimensional unmet needs questionnaire, Functional
      Assessment of Cancer Therapy (FACT-G), Memorial Symptom Assessment Scale-Short
      Form (MSAS-SF) and other validated measurements of function, depression, health
      and social support. Multiple linear regression models were used to identify
      independent predictors of each unmet needs domain and of total unmet needs. The
      relationships between total unmet needs, QOL and multidimensional variables were
      also explored. The median number of total unmet needs was three, and the most
      frequently reported unmet needs areas were physical (80.0%), activities of daily
      living (53.3%), nutrition (46.1%) and emotional (32.5%). Different predictors of
      each unmet needs domain were identified. Younger age was associated with a higher
      risk of unmet needs in physical, economic and medical domains. Higher
      psychological symptom distress was associated with more unmet needs in the
      emotional/social, economic and medical domains. Physical symptom distress, extent
      of disease and health measure were only significant in the physical unmet needs
      domain. The depression, psychological and physical symptom distress scores,
      confident and affective social support scores, total unmet needs and age
      independently predicted FACT-G total QOL score (R(2)=63%, P < 0.00001). Patients
      with higher psychological, physical symptom distress and depression scores,
      younger age, lower functional status and metastatic disease were more likely to
      report more unmet needs. The total number of unmet needs was predictive of QOL.
      The unmet needs and QOL outcomes model was developed but needs further
      validation.

PMID- 15504620
TI  - Prostate cancer in African Americans: relationship of patient and partner self
      efficacy to quality of life.
AB  - This study examined the relationship between patient and partner ratings of self
      efficacy for symptom control and quality of life (QOL) among 40 African American
      prostate cancer survivors and their intimate partners. Data analyses revealed
      that cancer survivors who had rated their self-efficacy for symptom control
      higher reported better QOL related to urinary, bowel, and hormonal symptoms and
      better general health QOL (i.e., better physical functioning and better mental
      health). Data analyses also revealed that partners who rated their self-efficacy
      for helping the patient manage symptoms as higher reported better QOL (i.e., less
      negative mood and less caregiver strain). Finally, exploratory analyses indicated
      that higher self-efficacy in patients was associated with less anxiety and
      caregiver strain in partners, and higher self-efficacy in partners was associated
      with better adjustment to bowel and hormonal symptoms and better mental health in
      patients. The clinical implications of these findings are discussed and future
      directions for research on self-efficacy in African American prostate cancer
      survivors are identified.

PMID- 15504621
TI  - Palliative sedation to relieve psycho-existential suffering of terminally ill
      cancer patients.
AB  - To clarify the prevalence and the characteristics of patients who received
      palliative sedation therapy for psycho-existential suffering, a questionnaire was
      sent to 105 responsible physicians at all certified palliative care units in
      Japan. The participants were requested to report the number of patients who
      received continuous deep sedation for refractory psycho-existential suffering
      during the past year, and to provide details of the 2 most recent patients. A
      total of 81 physicians returned questionnaires (response rate, 80%). Twenty-nine
      physicians (36%) reported clinical experience in continuous deep sedation for
      psycho-existential suffering. The overall prevalence of continuous deep sedation
      was calculated as 1.0% (90 cases/8,661 total patient deaths), and a total of 46
      patient histories were collected. Performance status just before sedation was 3
      or 4 in 96%, and predicted survival was 3 weeks or less in 94%. The suffering
      requiring sedation was feeling of meaninglessness/worthlessness (61%), burden on
      others/dependency/inability to take care of oneself (48%), death
      anxiety/fear/panic (33%), wish to control the time of death by oneself (24%), and
      isolation/lack of social support (22%). Before sedation, intermittent sedation
      and specialized psychiatric, psychological, and/or religious care had been
      performed in 94% and 59%, respectively; 89% of 26 depressed patients had received
      antidepressant medications. All competent patients (n=37) expressed explicit
      requests for sedation, and family consent was obtained in all cases where family
      members were available (n=45). Palliative sedation for psycho-existential
      suffering was performed in exceptional cases in specialized palliative care units
      in Japan. The patient condition was generally very poor, and the suffering was
      refractory to intermittent sedation and specialized psychiatric, psychological,
      and/or religious care. Sedation was performed on the basis of patient and family
      consent. These findings suggest that palliative sedation for psycho-existential
      suffering could be ethically permissible in exceptional cases if the
      proportionality and autonomy principle is applied. More discussion about the role
      of palliative sedation therapy for refractory psycho-existential suffering in end
      of-life care is urgently necessary.

PMID- 15504622
TI  - Symptom experience of adult hospitalized medical-surgical patients.
AB  - The purpose of this study is to describe the symptom experience of adult patients
      hospitalized in medical/surgical units, to examine the relationship between
      demographic characteristics and symptom experience, and to explore the
      relationship between symptom severity and symptom distress. Utilizing the
      Memorial Symptom Assessment Scale (MSAS), patients (n=334) were asked to convey
      the presence or absence of each of 31 symptoms, the severity of the symptoms, and
      the degree to which the symptoms distressed or bothered them. Higher levels of
      symptom distress were found in women and in those who were unpartnered. The
      average number of symptoms reported per patient was 9.31 (SD=5.15), with a mean
      symptom distress rating of 1.8 (SD=0.84) and a mean symptom severity rating of
      1.65 (SD=0.83) on a 1-5 scale. The correlation between reports of symptom
      severity and symptom distress varied greatly by symptom, ranging from r=0.37 to
      r=0.82. This is the first study to examine the symptom prevalence, severity, and
      distress of hospitalized medical/surgical patients. The large sample size allowed
      for the detection of demographic differences in the reporting of symptom
      distress, and advances the current knowledge in the area.

PMID- 15504623
TI  - Perceptions of analgesic use and side effects: what the public values in pain
      management.
AB  - In this population-based telephone survey, we evaluated the attitudes of 302
      adults toward analgesic use and related side effects. Over half (68%) reported
      prior experience with 2 or more side effects. Vomiting (34%), confusion (32%),
      and nausea (17%) were ranked as the worst side effects. Exploratory cluster
      analysis grouped responses to 6 questions about willingness to use analgesics
      into two categories. Participants in Cluster I (n=106), "Conservatives," were
      less willing to take analgesics for pain as compared to those in Cluster II
      (n=153), "Liberals." Univariate analysis found Hispanics, women, those less
      affluent or educated, and those with prior side-effect experience were more
      likely to be Conservative. Experience with side effects (OR=1.3) and being female
      (OR=2.1) were the strongest predictors of conservative cluster membership. To
      achieve better pain outcomes, clinicians and patients must identify factors that
      contribute to conservative decision-making about analgesic use and side effect
      management.

PMID- 15504624
TI  - Acceptable, manageable, and tolerable days: patient daily goals for medication
      management of persistent pain.
AB  - Although the construct of "a symptom-free day" has been widely applied in asthma
      and gastric reflux disease, there is no analogous concept in the field of pain
      management. This study represents the initial development of a "day of acceptable
      or manageable pain control," a construct which reflects patients' daily strategic
      use of pain medication in order to allow the accomplishment of desired activities
      while minimizing side effects. Focus group methodology was used to extract
      patient-generated themes of "an acceptable day of pain control." Fifty-three
      outpatients with persistent moderate to severe average pain intensity due to
      osteoarthritis (n=18), metastatic cancer (n=15), and low back pain (n=20)
      participated. Participants preferred the term "manageable" or "tolerable" to
      "acceptable." Thematic analysis revealed components of a manageable/tolerable day
      of pain control as including: 1) taking the edge off the pain, 2) performing
      valued activities; 3) relief from dysphoria and irritability; 4) reduced
      medication side effects; 5) feeling well enough to socialize. Additional cancer
      specific themes included relief from fatigue and ability to have a positive day
      when one's future days were perceived as being limited. The set of themes is
      presented and their relevance for developing a measure of "a manageable day of
      pain control" discussed. Study findings identify a novel construct that can
      inform development of an outcome for evaluating the effectiveness of different
      pharmacotherapies for pain management.

PMID- 15504625
TI  - Opioids in renal failure and dialysis patients.
AB  - This article reviews the literature pertaining to the metabolism of several of
      the commonly used opioids, and the known activity of their metabolites. The
      effect of renal failure on the pharmacokinetics of these drugs and metabolites is
      then reviewed. Finally, the effect of renal dialysis on opioid drugs and
      metabolites is reviewed. Based on the review, it is recommended that morphine and
      codeine are avoided in renal failure/dialysis patients; hydromorphone or
      oxycodone are used with caution and close monitoring; and that methadone and
      fentanyl/sufentanil appear to be safe to use. Note is made that the "safe" drugs
      in renal failure are also the least dialyzable.

PMID- 15504626
TI  - Optimization of opioid therapy for preventing incident pain associated with bone
      metastases.
AB  - Breakthrough pain is a transitory flare of pain superimposed on an otherwise
      stable pain pattern in patients treated with opioids. One form of breakthrough
      pain is incident pain, which is due to movement and is commonly associated with
      bone metastases. The development of this pain is rapid and no medication,
      administered "as needed," has such a rapid onset that it parallels this temporal
      pattern of pain. This study used a construct based on the prevention of this
      event, and implemented a new experimental paradigm. Specifically, the study
      determined whether increasing the opioid doses above those sufficient to control
      pain at rest would reduce the occurrence of these pains. Twenty-five consecutive
      patients with movement-related episodic pain associated with bone metastases, and
      no evident fractures, were selected for the study. They received a rapid
      intravenous titration of the opioid dose to obtain pain relief at rest. Then,
      opioid doses were increased to challenge the therapeutic window. The dose ceiling
      was determined by the development of limiting adverse effects, rather than
      optimal pain control at rest. Opioid dose increases were then stopped, or doses
      were even reduced, according to patients' satisfaction or development of adverse
      effects with moderate-severe intensity. Basal pain intensity and pain induced by
      movement were measured using a numerical scale from 0-10. Opioid-related symptoms
      were assessed using a scale from 0 to 3 (absent, slight, moderate, severe), and
      global daily doses of oral morphine and other symptomatic drugs were also
      recorded at daily intervals, and at time of discharge, when the best balance was
      presumed to be reached. Basal pain control was achieved after rapid intravenous
      titration. The day after, pain induced by movement significantly improved using
      mean doses of oral morphine equivalents of 102 mg. In the following days, the
      subsequent increase in opioid doses prescribed despite optimal basal pain control
      allowed an acceptable level of incident pain intensity until patients' discharge.
      A minority of patients developed adverse effects with an intensity of 2-3 on the
      scale, requiring symptomatic treatment or decreases in opioid doses. Data from
      this study suggest that the intensity of incident pain may be reduced by
      increasing the opioid dose above that effective for controlling pain at rest.
      This approach is based on experimental bone models showing a hypersensitivity to
      some innocuous stimuli, such as movement, requiring pre-emptive higher doses of
      basal opioid medication to reduce the increased pain input.

PMID- 15504627
TI  - A randomized, double-blind, crossover study of the use of transcutaneous spinal
      electroanalgesia in patients with pain from chronic critical limb ischemia.
AB  - Transcutaneous spinal electroanalgesia (TSE) uses two electrodes placed over the
      skin of the dorsal spine to deliver pulses of short wavelength, high frequency,
      and relatively high voltage to the spinal cord without causing paresthesia. TSE
      has been used to treat pain and may improve limb blood flow. This randomized,
      double-blind, crossover study assessed the effect of TSE on microcirculation,
      pain, and activity in 8 patients (3 men, 5 women, median age 66.5 years, range 62
      76 years) with chronic critical limb ischemia (CLI). After a one-week baseline
      period, patients used an active or inactive TSE machine for one hour daily for
      one week. Following a week of no stimulation, patients repeated the week of
      treatment with an identical matched machine. Daily use of TSE for one week did
      not improve microcirculatory perfusion (transcutaneous oxygenation), pain (verbal
      rating scale, McGill Pain Questionnaire), physical function (Functional
      Limitations Profile), mood (Beck Depression Inventory, Beck Anxiety Inventory),
      or sleep. There was no patient preference for the active TSE machines. This study
      showed that TSE administered daily for one week did not improve microcirculation,
      pain, or activity in patients with chronic CLI.

PMID- 15504628
TI  - The experience of chronic severe pain in patients undergoing methadone
      maintenance treatment.
AB  - Recent studies indicate that severe chronic pain is common among patients in
      methadone maintenance treatment (MMT), but no qualitative studies have examined
      such patients' experiences of pain and pain treatment. This study used
      qualitative methods to explore the experiences of MMT patients with chronic pain.
      Twelve patients screening positive for chronic severe pain on the Brief Pain
      Inventory were interviewed for the study. Results suggest that chronic severe
      pain has major consequences in the lives of methadone maintenance patients and
      may be linked to illegal drug use, social isolation, and role failure. A variety
      of barriers limited access to effective treatment. A common complaint with care
      was providers' lack of concern or inability to "listen." Patients who were
      satisfied with treatment focuses on the psychosocial dimensions of care. These
      preliminary results suggest that treatment approaches should emphasize emotional
      support, negotiation of explanatory models, and an emphasis on the psychosocial
      sequelae of pain. However, more research is needed to guide the development of
      effective treatment strategies.

PMID- 15504629
TI  - Implementation of an ad hoc hospital-based palliative care consult service.

PMID- 15504630
TI  - A nested case-control study of influenza vaccination was a cost-effective
      alternative to a full cohort analysis.
AB  - OBJECTIVE: In the absence of trial results that are applicable to the target
      population, nested case-control studies might be an alternative to full-cohort
      analysis. We compared relative and absolute estimates of associations in an
      influenza vaccine study using both designs. STUDY DESIGN AND SETTING: Data from
      elderly persons enrolled during six consecutive influenza seasons were used
      (147,551 person-periods). The endpoints "hospitalization for pneumonia or
      influenza" (P&I) or "death" were used combined and separately to define three
      types of cases. Controls for the case-control samples were randomly selected from
      the remainder of the total cohort at different ratios (1:1 to 1:4). Logistic
      regression analysis was used to assess adjusted vaccine effectiveness (VE).
      Sampling fractions were used to determine the number needed to treat to prevent
      one outcome. Receiver-operator-curve analysis was conducted to estimate the area
      under the curve (AUC) as a measure of discriminative capacity of the prognostic
      model. RESULTS: In all, 978 P and I hospitalizations and 1,339 deaths were
      observed. The adjusted estimates of relative estimates (VE, AUC) and their
      corresponding 95% confidence intervals were virtually the same using both study
      designs, notably when the case-control ratio was high (1:4). CONCLUSION: A nested
      case-control design can provide valid and precise estimates of associations and
      is a cost-effective alternative for full-cohort analysis.

PMID- 15504631
TI  - The Health Technology Assessment-disease management instrument reliably measured
      methodologic quality of health technology assessments of disease management.
AB  - OBJECTIVE: Systematic reviews aim to summarize the evidence in a particular topic
      area, giving attention to the identified methodologic quality of published
      research. Because research in a specific area may be susceptible to specific
      biases, it is assumed that the methodologic quality of Health Technology
      Assessment (HTA) of disease management cannot properly be measured with the
      existing methodologic quality assessment instruments. The purpose of this study
      was to describe to what extent existing instruments are useful in assessing the
      methodologic quality of HTA of disease management. STUDY DESIGN AND SETTING: An
      inventory was made of the problems that arise when assessing the methodologic
      quality of six HTAs of disease management with three different instruments. Based
      on these findings, a new instrument is proposed and validated. RESULTS: Problems
      mainly concern the items related to the study design, criteria for selection and
      restriction of patients, baseline and outcome measures, blinding of patients and
      providers, and the description of (co)-interventions. CONCLUSION: With its more
      specific characteristics, the HTA-DM addresses the problems mentioned. The HTA-DM
      is a reliable instrument for methodologic quality assessment of HTA of disease
      management in comparison with the other three instruments.

PMID- 15504632
TI  - Incidence-based measures of birth, growth restriction, and death can free
      perinatal epidemiology from erroneous concepts of risk.
AB  - BACKGROUND: Traditional perinatal epidemiology appears to embrace fallacious
      concepts of risk. The use of incorrect denominators for perinatal rates is
      commonplace both for straightforward indices such as the gestational age-specific
      labor induction rate and also for the more conceptually challenging indices such
      as the gestational age-specific neonatal mortality rate. As a consequence,
      perinatology is beset by several conondrums including the paradox of intersecting
      perinatal mortality curves. PROPOSITION: These traditions are ideally replaced by
      alternative concepts that may be derived a priori and measured using indices such
      as presented here: the incidence of birth (i.e., the gestational age-specific
      birth rate), the incidence of growth restriction (i.e., the gestational age
      specific growth-restriction rate) and the incidence of death (i.e., the age
      specific mortality rate). RESULTS: The incidence of birth, growth restriction,
      and death quantify the core phenomena in perinatology and reveal congruent and
      coherent patterns of occurrence. CONCLUSIONS: These new indices can free
      perinatal epidemiology from erroneous concepts of risk and resolve the paradoxal
      phenomena that plague the perinatal domain. They also permit the development of a
      theoretical framework for obstetric intervention, which in recent years has been
      based exclusively on empirical evidence.

PMID- 15504633
TI  - A combination of distribution- and anchor-based approaches determined minimally
      important differences (MIDs) for four endpoints in a breast cancer scale.
AB  - OBJECTIVE: To determine distribution- and anchor-based minimal important
      difference (MID) estimates for four scores from the Functional Assessment of
      Cancer Therapy-Breast (FACT-B): the breast cancer subscale (BCS), Trial Outcome
      Index (TOI), FACT-G (the general version), and FACT-B. STUDY DESIGN AND SETTING:
      We used data from a Phase III clinical trial in metastatic breast cancer (ECOG
      study 1193; n=739) and a prospective observational study of pain in metastatic
      breast cancer (n=129). One third and one half of the standard deviation and 1
      standard error of measurement were used as distribution-based criteria. Clinical
      indicators used to determine anchor-based differences included ECOG performance
      status, current pain, and response to treatment. RESULTS: FACT-B scores were
      responsive to performance status and pain anchors, but not to treatment response.
      By combining the results of distribution- and anchor-based methods, MID estimates
      were obtained: BCS=2-3 points, TOI=5-6 points, FACT-G=5-6 points, and FACT-B=7-8
      points. CONCLUSION: Distribution- and anchor-based estimates of the MID do show
      convergence. These estimates can be used in combination with other measures of
      efficacy to determine meaningful benefit and provide a basis for sample size
      estimation in clinical trials.

PMID- 15504634
TI  - Sensitivity analyses allowed more appropriate and reliable meta-analysis
      conclusions for multiple outcomes when missing data was present.
AB  - OBJECTIVE: A major problem for meta-analysis of multiple outcomes is the
      unavailability of some estimates from published and unpublished studies.
      Dissemination bias, in how and what outcomes are reported or published, may be
      causing this incompleteness. This article illustrates these problems and presents
      possible sensitivity analyses to allow the most reliable conclusions. STUDY
      DESIGN AND SETTING: In a systematic review of prognostic marker MYC-N in
      neuroblastoma, meta-analysis for overall survival (OS) and disease-free survival
      (DFS) was of interest. Only 17 published studies enabled extraction of both
      outcome estimates, 25 enabled only DFS, 39 enabled only OS, and 70 enabled
      neither outcome. Unidentified unpublished studies may also exist. We assessed the
      robustness of the pooled estimates to the problem of missing information. Because
      OS and DFS estimates seemed to be related, we used the known outcome estimates to
      predict estimates known to be missing, and combined this approach with existing
      methods for assessing dissemination bias. RESULTS: The results of the sensitivity
      analyses suggested that the original meta-analysis results were likely to be an
      overestimate of the true OS and DFS effect-sizes but strengthened the belief that
      MYC-N is a potentially important prognostic marker in neuroblastoma. CONCLUSION:
      Sensitivity analyses in meta-analysis allow more appropriate and reliable
      conclusions when problems such as unavailable estimates and dissemination bias
      are present.

PMID- 15504635
TI  - Empirical Bayes estimates generated in a hierarchical summary ROC analysis agreed
      closely with those of a full Bayesian analysis.
AB  - BACKGROUND AND OBJECTIVE: A range of fixed-effect and random-effects meta
      analytic methods are available to obtain summary estimates of measures of
      diagnostic test accuracy. The hierarchical summary receiver operating
      characteristic (HSROC) model proposed by Rutter and Gatsonis in 2001 represents a
      general framework for the meta-analysis of diagnostic test studies that allows
      different parameters to be defined as a fixed effect or random effects within the
      same model. The Bayesian method used for fitting the model is complex, however,
      and the model is not widely used. The objective of this report is to show how the
      model may be fitted using the SAS procedure NLMIXED and to compare the results to
      the fully Bayesian analysis using an example. METHODS: The HSROC model, its
      assumptions, and its interpretation are described. The advantages of this model
      over the usual summary ROC (SROC) regression model are outlined. A complex
      example is used to compare the estimated SROC curves, expected operating points,
      and confidence intervals using the alternative approaches to fitting the model.
      RESULTS: The empirical Bayes estimates obtained using NLMIXED agree closely with
      those obtained using the fully Bayesian analysis. CONCLUSION: This alternative
      and more straightforward method for fitting the HSROC model makes the model more
      accessible to meta-analysts.

PMID- 15504636
TI  - Characteristics of childhood cancer survivors predicted their successful tracing.
AB  - OBJECTIVE: The Childhood Cancer Survivor Study is a retrospective cohort study
      that was initiated to explore late effects of childhood cancer and its therapies.
      We evaluated the characteristics of those requiring tracing and factors that
      influenced tracing success. STUDY DESIGN AND SETTING: Medical record review
      identified 20,051 eligible individuals from 25 institutions in the United States
      and Canada. Of these, 13,021 had a current address in the medical record at the
      treating institution, and 7,030 had an incorrect address and required tracing by
      a commercial firm. RESULTS: Tracing was successful for 4,188 persons (60%).
      Younger age at contact, shorter length of time since last contact, having a
      middle initial available, an uncommon last name, and socioeconomic factors were
      found to predict successful tracing. Compared to those with a current address
      available in medical records, subjects successfully traced were less likely to
      have accessed health care during the previous 2 years; and more likely to be
      current smokers, obese, and to report moderate to severe impairments (pain,
      functional status, and activity). CONCLUSION: These findings provide an empirical
      basis concerning determinants and predictors of tracing success. If tracing had
      not been performed in this cohort, spurious associations may have been obtained
      for some health outcomes of interest.

PMID- 15504637
TI  - Education was associated with injuries requiring hospital admission.
AB  - OBJECTIVES: We describe educational inequalities in the incidence of injuries
      resulting in hospital admission and explore the contribution of exposure
      variables and chronic diseases, alcohol consumption, and sedative use to the
      observed inequalities. STUDY DESIGN AND SETTING: Data from the Dutch prospective
      GLOBE study were linked to the National Hospital Discharge Register after 7 years
      of follow-up. RESULTS: Significantly higher hazard ratios (HRs) of traffic
      injuries in lower compared with higher educational groups were substantially
      reduced after adjustment for differences in the use of cars and mopeds between
      these groups. Significantly increased HRs in occupational, home, and sports (OHS)
      injuries in lower compared with higher educational groups were reduced after
      adjustment for higher prevalence rates of chronic diseases, very excessive
      alcohol consumption, and sedative use in lower educational groups. CONCLUSION:
      Exposure variables, chronic diseases, alcohol consumption, and sedative use
      contribute to educational inequalities in traffic and OHS injuries resulting in
      hospital admission.

PMID- 15504638
TI  - Hypertension, diabetes, hypercholesterolemia, and their combinations increased
      health care utilization and decreased health status.
AB  - BACKGROUND AND OBJECTIVE: For individuals with hypertension, diabetes, or
      hypercholesterolemia, the relative magnitude of cardiovascular risk factors and
      the effect of multiple risk factors remains controversial and both treatment
      practices and health care usage vary. We sought to determine the effect of
      hypertension, diabetes, hypercholesterolemia, and their combinations on health
      care utilization and health status through analysis of data from a large national
      survey. METHODS: We applied the Anderson model to a cross-sectional
      representative sample (n=15,107) of the U.S. civilian, noninstitutionalized
      population (the 1996 Medical Expenditure Panel Survey). RESULTS: For diabetes,
      additional risk factors did not increase the likelihood of emergency room (ER)
      visits or hospitalizations but were associated with increased outpatient visits
      and poorer health status. For hypertension, additional risk factors increased the
      likelihood of hospitalization (but not ER visits), the number of outpatient
      visits, and poorer health status. For hypercholesterolemia, additional risk
      factors were associated with increased likelihood of ER visits, hospitalizations,
      and poorer health status but not more outpatient visits. Diabetes had the largest
      effect on health care utilization and health status. CONCLUSION: These findings
      re-emphasize the magnitude of diabetes as a major risk factor associated with
      increased ER visits, hospitalizations, outpatients visits, and lower health
      status.

PMID- 15504639
TI  - Pharmacy and medical claims data identified migraine sufferers with high
      specificity but modest sensitivity.
AB  - OBJECTIVE: Claims data are often used to identify and monitor individuals with
      particular conditions, but many health conditions are not easily recognizable
      from claims data alone. Patient characteristics routinely available in claims
      data were used to develop model-based claims signatures to identify migraineurs.
      STUDY DESIGN AND SETTING: A validated telephone interview was administered to
      23,299 continuously enrolled managed care members aged 18-55 to identify 1,265
      migraineurs and 1,178 controls. Responses were linked to medical and prescription
      claims. Claims variables were evaluated for sensitivity, specificity, and
      positive and negative predictive value in predicting migraine status. Regression
      models for predicting migraine status were developed. RESULTS: Regression-based
      claims signature models were successful in case-finding, as indicated by fairly
      sizable odds ratios (OR). In the full model (including demographic, medical,
      pharmacy, and comorbidity claims variables), a claim for a migraine drug, gender,
      and a claims-based headache diagnosis were strongly associated with migraine case
      status (OR=3.9, 3.2, and 3.0, respectively). CONCLUSION: Using either medical or
      pharmacy claims provided highly specific and moderately sensitive case-findings.
      Strategies that combined medical and pharmacy information improved sensitivity
      and may increase the usefulness of claims for identifying migraine and improving
      the quality of migraine care.

PMID- 15504640
TI  - Misclassification of exposure is high when interview data on drug use are used as
      a proxy measure of chronic drug use during follow-up.
AB  - BACKGROUND AND OBJECTIVE: In many observational studies, the association between
      drugs and disease is analyzed with information from a baseline interview. We
      investigated the magnitude and direction of exposure misclassification by
      comparing interview data at baseline with prospectively gathered pharmacy data.
      METHODS: The study population for this study consisted of a cohort of 2,487
      participants aged 71 years or older from the Rotterdam Study. Data on drug use
      were gathered at the baseline interview and through pharmacies during the follow
      up period between January 1, 1991, and January 1, 1999. We assessed the
      sensitivity, specificity, and positive and negative predictive value of interview
      data as proxy measures of chronic use of calcium channel blockers (CCB) in
      comparison with longitudinal medication records from the pharmacy. RESULTS: Only
      3 of the 206 subjects (1.5%) who reported use at baseline did not use CCBs during
      follow-up. Of the 2,281 persons who reported no use of CCBs at baseline, however,
      354 actually used CCBs during follow-up (15.5%). The difference between interview
      data and pharmacy records corresponded to a misclassification bias of 0.73
      (95%CI: 0.52-1.02). CONCLUSION: Misclassification of exposure was high when
      interview data were used as a proxy measure of chronic use during follow-up.

PMID- 15504641
TI  - Individuals with type 2 diabetes and depressive symptoms exhibited lower
      adherence with self-care.
AB  - OBJECTIVE: Our study aimed to determine whether depressive symptoms are
      associated with poor self-care behaviors among patients with type 2 diabetes.
      METHODS: Study subjects were 168 patients with diabetes, aged >30 years, who had
      a diabetes history of 1-15 years. Using a self-reported questionnaire, we
      evaluated diabetes self-care behaviors and depressive symptoms. Self-care
      behaviors were evaluated in five categories: medication taking, self-monitoring
      of blood glucose (SMBG), diet, exercise, and participation in patient education
      programs. Depressive symptoms were evaluated using the Centers for Epidemiologic
      Studies-Depression (CES-D) scales. Multiple logistic regression analyses were
      used to determine the association between self-care behaviors and depressive
      symptoms. RESULTS: Higher depressive-symptom scores were associated with poor
      self-care behaviors, significantly with poor participation in education programs
      (odds ratio OR=1.21, 95% confidence interval CI=1.06-1.38) and poor diet
      (OR=1.11, 95% CI=1.01-1.22), and marginally with poor medication taking (OR=1.14,
      95% CI=1.00-1.31). Depressive symptoms were not significantly associated with
      either SMBG or exercise. CONCLUSIONS: These data suggest that the evaluation and
      control of depressive symptoms among diabetic patients would improve their
      adherence to self-care behaviors.

PMID- 15504642
TI  - ICD-9-CM codes poorly indentified venous thromboembolism during pregnancy.
AB  - OBJECTIVE: There is little data regarding the accuracy of pregnancy-specific ICD
      9-CM codes used to identify patients with venous thromboembolism (VTE). STUDY
      DESIGN AND SETTING: We identified a large cohort of pregnant patients in whom
      there were one or more pregnancy-specific (600 codes) or standard ICD-9-CM codes
      (400 codes) for VTE. Charts of these cases were abstracted to determine the
      presence of objectively documented VTE. RESULTS: A total of 214 cases had a code
      for VTE either during pregnancy or the 6-week postpartum period; 82% had a
      pregnancy-specific code and 18% a standard code. Overall, 84 (39%, 95% CI=33-46%)
      had objectively documented VTE. A pregnancy-specific ICD-9-CM for VTE had a
      positive predictive value (PPV) of 54/174=31% (95% CI=24-38%), whereas standard
      VTE codes had a PPV of 30 of 38=80% (95% CI=63-99%). A PPV in the range of 95
      100% could be attained using other criteria, at the expense of detecting only 28
      to 45% of all VTE cases. CONCLUSIONS: Pregnancy-specific ICD-9-CM codes for VTE
      have low PPV. Other criteria must be applied to select cases with a high
      probability of having objectively documented VTE.

PMID- 15504643
TI  - Comment on the comparison of test-retest reliabilities for 2-day and 2-week
      intervals.

PMID- 15504645
TI  - A study of the family burden of 150 family members of schizophrenic patients.
AB  - PURPOSE: Investigation into the family burden (FB) of schizophrenic patients has
      recently risen sharply. Nevertheless, to date there has been little consensus as
      to what factors influence the FB. The purpose of this study is to acquire a
      greater insight into the variables that influence the FB. SUBJECTS/METHODS: The
      FB was measured with the interview for the family burden (Kluiter H, Kramer JJAM,
      Wiersma D, et al. Interview voor de belasting van de familie 1997 [Interview for
      the burden on the family]. Department Sociale Psychiatrie. Groningen:
      Rijksuniversiteit). One hundred and fifty family members (parents/partners) of
      schizophrenic patients participated in the study. RESULTS: The results of our
      study show (1) that family members experience burden both on a practical and an
      emotional level, (2) a highly significant correlation between the amount of
      symptomatic behaviour of the patient and FB, (3) that parents had taken on more
      tasks, had contributed more financially and had experienced a tenser atmosphere
      at home than partners did and (4) that family members of patients who have been
      treated for less than 1 year worry more about the other members of their family
      than family members of patients who have been receiving treatment for more than 1
      year. CONCLUSIONS: Family members of schizophrenic patients experience burden on
      a practical, financial and emotional level and the extent of the burden is
      closely linked to the amount of symptomatic behaviour of the patient.

PMID- 15504646
TI  - Appraisal of caregiving, burden and psychological distress in relatives of
      psychiatric inpatients.
AB  - Appraisal of caregiving and its relationship to family burden and experienced
      mental health problems in the relatives were investigated as part of a multi
      centre study of the quality of mental health services in Sweden performed in
      1997. The sample was drawn from relatives of involuntarily and voluntarily
      admitted patients to acute psychiatric wards. The instrument used was a semi
      structured questionnaire, interviewing relatives about the burden, experience of
      mental health problems and appraisal of the caregiving situation. The results
      showed a high proportion of relatives engaged in caregiving activities on a daily
      basis the month before the patient's admission to hospital and a high proportion
      of relatives appraising the caregiving activities negatively. The burden was more
      extensive if the relative and the patient were living together, had a longer
      duration of their relationship, if the relative was rendering caregiving on a
      daily basis and if the relative appraised caregiving negatively. The relatives'
      psychological distress was not related to their negative appraisal of caregiving,
      nor was patient characteristics, such as diagnosis and level of psychosocial
      functioning. The only factor found to influence the relatives' psychological
      distress was the duration of relationship to the patient. Interventions reducing
      psychological distress for relatives who have known the patients for more than 20
      years, who live with the patient, who give care on a daily basis and who appraise
      their caregiving negatively are suggested.

PMID- 15504647
TI  - Family disruption, economic hardship and psychological distress in schizophrenia:
      can they be measured?
AB  - This study examined the dimensions of burden perceived by key-relatives of
      patients suffering from schizophrenia spectrum disorder by the development of an
      instrument, the Family Burden Scale (FBS) and the underlying predictors. One
      hundred and seventy one primary caregivers, living with 158 patients suffering
      from chronic psychotic illness and maintained on community basis in Athens area,
      were interviewed by the use of FBS supplemented by the Family Atmosphere Scale
      and GHQ. Construction procedure and factor analysis of FBS produced a scale of 23
      items in four factors, three of them measuring objective and the fourth one,
      subjective burden. The scale was also proved to be reliable and valid. Forty-five
      percent of primary caregivers reported high levels of burden. Psychological
      impairment (high GHQ scores) was related with high levels of burden and negative
      family atmosphere. Previous admissions and duration of illness were also found to
      predict burden. The results suggest that FBS differentiates objective from
      subjective burden. Psychological well being of carers is affected by the
      dimensions of perceived burden.

PMID- 15504648
TI  - Impact of present and past antipsychotic side effects on attitude toward typical
      antipsychotic treatment and adherence.
AB  - OBJECTIVE: (1) determine which antipsychotic side effects (SE) schizophrenic
      patients consider the most distressing during treatment with typical
      antipsychotics, (2) measure the impact of actual and past SE on patients'
      attitude toward antipsychotics and (3) assess the influence of both on adherence.
      METHODS: The 213 schizophrenics, treated with conventional antipsychotics, were
      recruited in two psychiatric hospitals in Hamburg. Subjects were assessed about
      type and severity of present and past side effects and their attitude and
      adherence to antipsychotic treatment. RESULTS: The 82 (39%) patients presented
      present SE while 131 (61%) did not. Sexual dysfunctions (P < 0.001),
      extrapyramidal (P < 0.05) and psychic side effects (P < 0.05) were rated as
      significantly subjectively more distressing than sedation or vegetative side
      effects. Patients presenting with present SE compared with patients without
      present SE had a significantly more negative general attitude toward
      antipsychotics (P < 0.05), were more doubtful about their efficacy (P < 0.01) and
      were less likely to encourage a relative to take such a medication in case of
      need (P < 0.001). A regression analysis indicated that nonadherence was mainly
      influenced by negative general and efficacy attitudes toward antipsychotics and
      the experience of past or present antipsychotic side effects. CONCLUSIONS: All
      antipsychotic side effects, present or past, can have a durable negative impact
      on patient's attitude toward antipsychotic treatment and adherence. Non-adherence
      is mainly determined, among other factors, by these negative attitudes, which are
      partly influenced by the experience of past or present antipsychotic-induced side
      effects.

PMID- 15504649
TI  - What about psychiatrists' attitude to mentally ill people?
AB  - OBJECTIVE: Firstly, to assess and, secondly, to compare experts' and lay
      attitudes towards community psychiatry and the respective social distance towards
      mentally ill people. METHOD: Comparison of two representative Swiss samples, one
      comprising of 90 psychiatrists, the other including 786 individuals of the
      general population. RESULTS: The psychiatrists' attitude was significantly more
      positive than that of the general population although both samples have a
      positive attitude to community psychiatry. The statement that mental health
      facilities devalue a residential area has revealed most agreement. Psychiatrists
      and the public do not differ in their social distance to mentally ill people.
      Among both samples, the level of social distance increases the more the situation
      described implies "social closeness". CONCLUSION: The strategy to use
      psychiatrists as role models or opinion leaders in anti-stigma campaigns cannot
      be realised without accompanying actions. Psychiatrists must be aware that their
      attitudes do not differ from the general public and, thus, they should improve
      their knowledge about stigma and discrimination towards people with mental
      illnesses.

PMID- 15504650
TI  - Sterilisation of intellectually disabled women.
AB  - OBJECTIVE: To point out the proportion of intellectually disabled women (IDW) who
      are sterilised, and the medical and social factors associated with an increased
      probability to be sterilised. STUDY DESIGN: A population-based study among 97% of
      IDW aged 18-46, attending government-accredited institutions in the region of
      Brussels-Capital and the province of Walloon Brabant (Belgium). RESULTS: Among
      the IDW included in this study, 22.2% are sterilised, which is superior to the 7%
      in the general Belgian population. Factors associated with an increased
      probability to be sterilised are: living in an institution, having a higher
      intellectual quotient (IQ), being enrolled in an institution where sexual
      intercourse is authorised and attending an institution where contraception is
      required. The last three factors are significant only among women living in
      institutions and the last two, only in women with severe disability. Among IDW
      using contraception, no factor was associated with a greater probability to be
      sterilised. CONCLUSION: The prevalence of sterilisation among IDW is three times
      higher than that in the Belgian population and it is mainly correlated with
      factors related to the institution where these women live, especially the
      severely disabled.

PMID- 15504651
TI  - Neurological soft signs in homicidal men with antisocial personality disorder.
AB  - Neurological soft signs (NSS) are characterized by abnormalities in motor,
      sensory, and integrative functions. NSS have been regarded as a result of
      neurodevelopmental dysfunction, and as evidence of a central nervous system
      defect, resulting in considerable sociopsychological dysfunction. During the last
      decade there has been growing evidence of brain dysfunction in severe aggressive
      behavior. As a symptom, aggression overlaps a number of psychiatric disorders,
      but it is commonly associated with antisocial personality disorder. The aim of
      the present study was to examine NSS in an adult criminal population using the
      scale by Rossi et al. [29]. Subjects comprised 14 homicidal men with antisocial
      personality disorder recruited from a forensic psychiatric examination. Ten age-
      and gender-matched healthy volunteers as well as eight patients with
      schizophrenia, but no history of physical aggression, served as controls. The NSS
      scores of antisocial offenders were significantly increased compared with those
      of the healthy controls, whereas no significant differences were observed between
      the scores of offenders and those of patients with schizophrenia. It can be
      speculated that NSS indicate a nonspecific vulnerability factor in several
      psychiatric syndromes, which are further influenced by a variety of genetic and
      environmental components. One of these syndromes may be antisocial personality
      disorder with severe aggression.

PMID- 15504652
TI  - Hippocampal volume and subjective memory impairment in depressed patients.
AB  - The relationship between severity of subjective memory impairment and volume of
      the hippocampus/amygdala complex was investigated in non-demented depressed
      patients and it was found to correlate with decreasing volume in the right
      hippocampus.

PMID- 15504653
TI  - Object alternation test--is it sensitive enough to detect cognitive dysfunction
      in obsessive-compulsive disorder?
AB  - A computerized version of the object alternation test (OAT) was employed in
      unmedicated obsessive-compulsive disorder (OCD) patients and matched healthy
      controls. OCD patients performed normally on the OAT but scored below controls on
      a task assessing visuo-spatial working memory. The results challenge the concept
      of the OAT as a sensitive instrument for orbitofrontal dysfunction in OCD.

PMID- 15504654
TI  - Trends in the use of the Italian Mental Health Act, 1979--1997.
AB  - Italian statistics on psychiatric bed availability, voluntary and compulsory
      admissions were examined from 1979 to 1997. Although the number of psychiatric
      beds dropped by 62.5%, the absolute number of compulsory admissions has remained
      substantially stable. The proportion of all admissions that were compulsory
      decreased from 17.1% to 11%. This study shows that a shift to community care was
      not associated with an increase in compulsory admissions in Italy.

PMID- 15504655
TI  - Depression and associated organic diseases: are there any specific depressive
      symptoms? Results from the dialogue-2 survey.
AB  - The objective of the survey was to compare depressive symptoms in depression with
      and without a concomitant organic disease. The results based on the HAD and CES-D
      scales showed that, compared to those with an isolated depression, the patients
      with an associated chronic organic disease have a higher score on two items on
      the HAD. Three variables on the CES-D scale also helped to differentiate the two
      groups of depressed patients. No significant difference was found between the two
      groups in terms of anxiety or cognitive symptoms, fatigue or feelings of
      disability. Our results do not indicate any symptom that is specific to a
      combination of depression and somatic diseases. Guilt and hostility showed a
      lower level in depression associated with a concomitant somatic disease than in
      isolated depression.

PMID- 15504656
TI  - Differential effects of milnacipran, fluvoxamine and paroxetine for inhibited and
      agitated depression.

PMID- 15504657
TI  - Risperidone-induced rabbit syndrome in mood disorder.

PMID- 15504658
TI  - Amisulpride-associated pedal edema.

PMID- 15504659
TI  - Post-stroke depression and cerebral laterality.

PMID- 15504660
TI  - Antidepressant-associated mania with escitalopram.

PMID- 15504661
TI  - Serotonin syndrome due to association of venlafaxine, maprotiline and reboxetine.

PMID- 15504662
TI  - Dental pain during repetitive transcranial magnetic stimulation.

PMID- 15504663
TI  - Bioreactor landfills: progress continues.

PMID- 15504664
TI  - Maximising household waste recycling at civic amenity sites in Lancashire,
      England.
AB  - In the UK, all local authorities have been set statutory performance standards
      for the recycling and composting of household waste. As part of their strategy
      for achieving these standards, Lancashire County Council (LCC) has made a number
      of alterations to the layout and facilities available at civic amenity sites
      (renamed Household Waste Recycling Centres (HWRCs)) in the county and tried to
      create a more positive image of the sites for members of the public. This study
      consisted of two surveys carried out in order to establish how to maximise
      household waste recycling at the 26 HWRCs in Lancashire. A telephone survey was
      carried out amongst all Lancashire's HWRC attendants in order to establish the
      effects of recent site improvements and to provide an indication of overall
      customer satisfaction. An on-site questionnaire survey was conducted amongst HWRC
      customers on five selected sites, over three separate seasons, incorporating
      comparative weekend and weekday surveys at each site. This survey investigated
      public opinion of HWRCs in Lancashire, as well as exploring effective methods
      that would assist customers in maximising the amount of recycling at HWRCs. The
      attendants' survey revealed that site attendants were actively encouraging
      customers to segregate waste more efficiently at the HWRCs, and that a recycling
      related bonus scheme had provided an incentive towards this effort. Site
      attendants have a key role in educating the public about waste segregation and
      the effective use of HWRCs. Lancashire HWRC users were mostly male, used private
      cars to transport waste and showed high levels of customer satisfaction.
      Practical changes to encourage more recycling at HWRCs were clearly identified in
      the customers' survey; these include longer opening hours and the provision of
      boxes to enable pre-separation of waste. The study has clearly shown how the
      results of user surveys can provide practical assistance in the development of
      improved sustainable waste management strategies.

PMID- 15504665
TI  - Production of activated carbons from waste tire--process design and economical
      analysis.
AB  - The process design and economic analysis of process plants to produce activated
      carbons from waste tires and coal have been performed. The potential range of
      products from each process has been considered, namely for waste tire--pyro-gas,
      active carbon, carbon black and pyro-oil; for coal--pyro-gas and active carbons.
      Sensitivity analyses have been carried out on the main process factors; these are
      product price, production capacity, total production cost, capital investment and
      the tipping fee. Net present values for the two plants at various discount
      factors have been determined and the internal rates of return have been
      determined as 27.4% and 18.9% for the waste tire plant and the coal plant,
      respectively.

PMID- 15504666
TI  - Energy conservation and CO2 emission reductions due to recycling in Brazil.
AB  - The present paper aims to make the energy saving potential provided by waste
      recycling in Brazil evident by pointing out more specifically the benefits
      regarding climate change mitigation. In this case, based on the energy saved due
      to the recycling process of an exogenous amount of waste, we have built two
      scenarios in order to show the potential for indirectly avoiding CO2 emissions in
      the country as a result of the recycling process. According to the scenario, 1 Mt
      and 3.5 Mt of CO2, respectively, would be avoided per year due to solid waste
      recycling. The international context for greenhouse gas emissions reduction, such
      as the United Nations Framework Convention on Climate Change and its Kyoto
      Protocol has been taken into account.

PMID- 15504667
TI  - Characterization of bottom ash in municipal solid waste incinerators for its use
      in road base.
AB  - Incineration of municipal solid wastes (MSWs) produces by-products which can be
      broadly classified as bottom and fly ashes. Since MSW incineration started,
      possibilities other than landfilling the incineration residues have been sought;
      most initiatives in this sense tend to use these residues as aggregate substitute
      in pavements and other road construction elements. The main goal of the present
      work is the physical and chemical characterization of the local incineration
      bottom ash towards its eventual re-utilization. The study includes not only the
      specific aspects regarding its role as pavement element, but also the assessment
      of the environmental effects. Therefore, together with the determination of
      physical (moisture content, apparent and bulk densities, crystallinity, etc.) and
      engineering properties (particle size distribution, abrasion and impact
      resistance, etc.), full chemical characterization of the bottom ash and the study
      of leaching as a function of aging time have been undertaken. The results
      obtained indicate that the metal content of both the raw bottom ash and its
      leachates fulfill the environmental regulations provided that the bottom ash is
      stored for at least one month. Engineering properties of the bottom ash are close
      to those of natural aggregates and, thus, road-construction use of these residues
      seems to be feasible.

PMID- 15504668
TI  - Use of recycling stations in Borlange, Sweden--volume weights and attitudes.
AB  - This paper presents a study of recycling stations in the municipality of
      Borlange, Sweden. The main objectives were to measure volume weights of
      recyclables, to facilitate future planning of collection intervals and
      bin/container volume, and to investigate the general attitudes among the public
      towards waste management in general and recycling stations in particular. Volume
      weights measured in bins/containers were: paper/newsprint: 297 kg/m3, glass
      packaging: 297 kg/m3, metal packaging: 81.7 kg/m3, paper packaging: 27.8 kg/m3,
      plastic packaging: 28.1 kg/m3. The recycling stations have been in use since
      1994. Most visitors (90%) arrived by car but said the visit to the recycling
      station was not the main purpose of the trip. The results from the interviews
      indicated that the people who use the recycling stations have found ways to
      incorporate waste sorting into their everyday lives, with the help of
      information, design of the collection system and environmental concerns.

PMID- 15504669
TI  - Microbiological characterization of food residues for animal feeding.
AB  - A description is offered of microbiological characterization of the biodegradable
      fractions present in food wastes so that those fractions can be transformed in
      such a way that they will fulfil the specifications involved in their use as raw
      materials in other production areas. In this way the wastes can be converted into
      sub-products, hence minimizing the amount of them eventually sent to rubbish
      dumps. Of all the types of residues analyzed, only those obtained by separate
      collection from fishmongers' and greengrocers' sections of large supermarkets and
      small shops were valid for the objectives of the project and were subjected to a
      heat treatment to test whether or not this treatment was capable of reducing
      their microbiological content to the point of converting them into acceptable raw
      materials for animal feed. Residues from butchers' sections of supermarkets and
      small shops, and residues from restaurants were not included in the final study
      because of the prohibition by the European legislation in force of using any kind
      of meat containing wastes for feeding farm animals. In the present work we made a
      one-year analysis of representative samples of such wastes. We observed that
      after thermal treatment at a temperature of at least 65 degrees C for 20 min the
      nutritional and microbiological parameters remained suitable for their possible
      use as animal feed and that their harmlessness was ensured, with no loss of
      nutritional characteristics. Regarding the microbiological study of the meals
      which have been obtained from residues for the production of the feed and the
      feed itself, and in accordance with the data for nutritional composition, we
      consider valid and sanitarily adequate their use as animal feed with the
      concomitant consequent minimization of waste, which has become a priority in view
      of the recent legislation enacted by the European Union.

PMID- 15504670
TI  - Disposal frequencies of selected recyclable wastes in Dar es Salaam.
AB  - A statistical survey of households based upon questionnaires distributed via
      primary schools has been carried out in five wards of Dar es Salaam, Tanzania, to
      estimate disposal frequencies (number of items disposed per week) for newsprint,
      metal cans, glass and plastic containers and plastic shopping bags. Plastic
      shopping bags are disposed most frequently while glass containers are disposed
      least frequently. The statistical distribution of disposal frequencies, which
      seems to be influenced by household income, is well described by Poisson
      distribution. Disposal frequencies are mutually correlated at 95% level of
      probability despite the differences in disposal patterns of individual
      households.

PMID- 15504671
TI  - Thermal valorization of footwear leather wastes in bubbling fluidized bed
      combustion.
AB  - Transformation of hide (animal skins) into leather is a complicated process
      during which significant amounts of wastes are generated. Footwear is the sector
      that consumes the major part of leather (60%). Logically, this industry is
      producing the largest quantity of leather wastes. The objective of this work was
      to demonstrate the technical feasibility of fluidized bed technology to recover
      the energy from burning footwear leather wastes. Considering the characteristics
      of leather waste, especially the heating value (12.5-21 MJ/kg), it can be
      considered a fairly good fuel. Moreover, leather waste has suitable
      characteristics for combustion, e.g., high volatile matter (76.5%) and low ash
      content (5.2%). Two factors deserve special attention: N3O and NOx emissions as a
      consequence of its unusual high nitrogen content (14.1%) and the chromium
      speciation because chromium is the main element of ash (3.2%) due to its use in
      leather tanning. A series of experiments has been carried out in a 0.1 MWt
      bubbling fluidized bed pilot plant. The combustion efficiency, flue gas
      composition and chromium speciation were investigated. Despite having high
      nitrogen content, a low conversion rate of fuel-N to NOx and N2O was attained.
      Chromium was concentrated in the solid streams and it was consistently found as
      Cr(III+); no presence of Cr(VI+) was detected.

PMID- 15504672
TI  - Leaching assessment of road materials containing primary lead and zinc slags.
AB  - Characterisation of the leaching behaviour of waste-containing materials is a
      crucial step in the environmental assessment for reuse scenarios. In our research
      we applied the multi-step European methodology ENV 12-920 to the leaching
      assessment of road materials containing metallurgical slag. A Zn slag from an
      imperial smelting furnace (ISF) and a Pb slag from a lead blast furnace (LBF) are
      investigated. The two slags contain up to 11.2 wt% of lead and 3.5 wt% of zinc
      and were introduced as a partial substitute for sand in two road materials,
      namely sand-cement and sand-bitumen. At the laboratory scale, a leaching
      assessment was performed first through batch equilibrium leaching tests. Second,
      the release rate of the contaminants was evaluated using saturated leaching tests
      on monolithic material. Third, laboratory tests were conducted on monolithic
      samples under intermittent wetting conditions. Pilot-scale tests were conducted
      for field testing of intermittent wetting conditions. The results show that the
      release of Pb and Zn from the materials in a saturated scenario was controlled by
      the pH of the leachates. For the intermittent wetting conditions, an additional
      factor, blocking of the pores by precipitation during the drying phase is
      proposed. Pilot-scale leaching behaviour only partially matched with the
      laboratory-scale test results: new mass transfer mechanisms and adapted
      laboratory leaching tests are discussed.

PMID- 15504673
TI  - Collection and transportation cost of household solid waste in Kuwait.
AB  - The specific aim of this funded research project was to examine and evaluate the
      efficiency and the effectiveness of the municipal solid waste collection and
      transportation system in the State of Kuwait. The contract resources of the seven
      contracting firms, the annual contract budgets, and the district area and
      population of each service contract are presented. Service efficiency and
      effectiveness indicators for each collection/disposal contract are also computed
      and discussed. The cost of collection and transportation of household waste in
      Kuwait is also compared with those of a number of urban areas in other nations.
      The low energy and manpower costs are mainly responsible for the favorable cost
      of management, collection and transportation of residential waste in Kuwait.

PMID- 15504674
TI  - A simple method to measure 13CH2 heteronuclear dipolar cross-correlation spectral
      densities.
AB  - Here, we report a method to simultaneously determine CH2 cross-correlation
      spectral densities and T1 relaxation times in the laboratory and rotating frames.
      To accomplish this, we have employed an indirect approach that is based on
      measurement of differences in relaxation rates acquired with and without cross
      correlation terms. The new method, which can be employed using multidimensional
      NMR and standard relaxation pulse sequences, is validated experimentally by
      investigation of a selectively 13C-enriched hexadecapeptide and the uniformly 13C
      enriched immunoglobulin-binding domain of streptococcal protein G (GB1). Use of
      this approach makes determination of CH2 cross-correlation spectral densities in
      uniformly 13C-enriched proteins now routine and provides novel information
      concerning their internal motions.

PMID- 15504675
TI  - Improved rejection of transmitter noise: a convenient scheme with resonant
      crossed diodes.
AB  - A method is presented for improved rejection of transmitter noise in the duplexer
      (transmit-receive switch). The capacitance of a set of crossed diodes forms a
      resonant circuit with a length of coaxial cable. The rejection of our resonant
      design is 60 dB, compared with only 12-15 dB for the usual method, all measured
      at 175 MHz. Tuning the entire duplexer to different frequencies is convenient,
      requiring only two new lengths of cable. The scheme is most useful with ungated
      linear rf power amplifiers at very high frequencies (above 100 MHz), where
      transmitter noise can be a severe problem.

PMID- 15504676
TI  - Switching-angle sample spinning NMR probe with a commercially available 20 kHz
      spinning system.
AB  - A switching-angle sample spinning (SASS) probe workable at high spinning speeds
      was developed using a commercially available rotor/housing system. Details of the
      construction are described. As application examples of the SASS probe, we report
      experiments of powder pattern separation at the spinning speed of 20 kHz and
      broadband 13C-13C polarization transfer at 16 kHz.

PMID- 15504677
TI  - A homodecoupled diffusion experiment for the analysis of complex mixtures by NMR.
AB  - Diffusion ordered spectroscopy (DOSY) relies on differences in translation
      diffusion as a means to separate components in a solution mixture. However, the
      analysis of spectra of mixtures can be problematic because spectral overlap. It
      is the aim of this article to propose a pulse sequence and processing method that
      leads to a complete 2D homodecoupled-DOSY experiment. This experiment offers
      several advantages that could extend the range of applications to more complex
      mixtures by achieving important improvements in both signal dispersion and
      sensitivity.

PMID- 15504678
TI  - A phase cycle scheme that significantly suppresses offset-dependent artifacts in
      the R2-CPMG 15N relaxation experiment.
AB  - R2-CPMG 15N relaxation experiments form the basis of NMR dynamics measurements,
      both for analysis of nano-pico second dynamics and milli-micro second dynamics
      (kinetics). It has been known for some time that in the practical limit of finite
      pulse widths, which becomes acute when using cryogenic probes, systematic errors
      in the apparent R2 relaxation behavior occur for spins far off-resonance from the
      RF carrier. Inaccurate measurement of R2 rates propagates into quantitative
      models such as model-free relaxation analysis, rotational diffusion tensor
      analysis, and relaxation dispersion. The root of the problem stems from evolution
      of the magnetization vectors out of the XY-plane, both during the pulses as well
      as between the pulses. These deviations vary as a function of pulse length,
      number of applied CPMG pulses, and CPMG inter-pulse delay. Herein, we analyze
      these effects in detail with experimentation, numerical simulations, and
      analytical equations. Our work suggests a surprisingly simple change in the phase
      progression of the CPMG pulses, which leads to a remarkable improvement in
      performance. First, the applicability range of the CPMG experiment is increased
      by a factor of two in spectral width; second, the dynamical/kinetic processes
      that can be assessed are significantly extended towards the slower time scale;
      finally, the robustness of the relaxation dispersion experiments is greatly
      improved.

PMID- 15504679
TI  - Line shapes of multiple quantum NMR coherences in one-dimensional quantum spin
      chains in solids.
AB  - General formulae for intensities of multiple quantum (MQ) NMR coherences in
      systems of nuclear spins coupled by the dipole-dipole interactions are derived.
      The second moments of the MQ coherences of zero- and second orders are calculated
      for infinite linear chains in the approximation of the nearest neighbor
      interactions. Supercomputer simulations of intensities of MQ coherences of linear
      chains are performed at different times of preparation and evolution periods of
      MQ NMR experiments. The second moments obtained from the developed theory are
      compared with the results of the supercomputer analysis of MQ NMR dynamics. The
      linewidth information in MQ NMR experiments is discussed.

PMID- 15504680
TI  - The 2D MAS NMR spin-echo experiment: the determination of 13C-13C J couplings in
      a solid-state cellulose sample.
AB  - A simple 13C MAS spin-echo experiment is applied to a partially 13C-labelled
      cellulose sample extracted from wood. 13C-13C J couplings are determined even
      though considerable chemical disorder leads to observed linewidths in the normal
      1D 13C CP MAS spectrum which far exceed the J couplings. The fitting of the
      experimental data also allows the quantification of the degree of isotopic
      enrichment.

PMID- 15504681
TI  - Enhancing sensitivity or resolution of homonuclear correlation experiment for
      half-integer quadrupolar nuclei.
AB  - We have recently introduced double-quantum homonuclear correlation NMR experiment
      for half-integer quadrupolar nuclei in solids, which was based on rotary
      resonance recoupling [J. Chem. Phys. 120 (2004) 2835]. In this contribution we
      show on two 23Na (I=3/2) containing samples, Na2SO4 and Na2HPO4, that the
      efficiency of the experiment can be substantially enhanced by adding rotor
      assisted population transfer (RAPT) and Carr-Purcell-Meiboom-Gill (CPMG)
      sequences to it. We also present an upgraded two-dimensional experiment, in which
      double- and six-quantum coherences are correlated during t1 evolution period,
      yielding a high-resolution isotropic spectrum along an indirectly detected
      dimension. The sensitivity of the upgraded experiment is, however, greatly
      reduced compared to the sensitivity of the original experiment, so that its
      application is feasible only when RAPT and CPMG can be used as well.

PMID- 15504682
TI  - A 'Hi-Fi' Cartesian feedback spectrometer for precise quantitation and superior
      performance.
AB  - The use of Cartesian electronic feedback for effecting a major improvement in the
      functioning of magnetic resonance instrumentation is reported. The dependences of
      both flip angle and signal strength upon probe loading, matching, and tuning are
      virtually eliminated. Thus, for a chosen probe, sample geometry and flip angle,
      the free induction decay signal strength is rendered solely dependent upon the
      number of nuclei. The instrument therefore becomes capable of absolute
      calibration. In addition, phase and amplitude distortion of selective pulses,
      introduced by crossed diodes, power amplifier heating, etc., is virtually
      eliminated, as are radiation damping and phase modulation caused by probe
      vibration. The use of multiple probes at the same frequency, for example
      quadrature probes and phased arrays, is also simplified as the effects of
      interactions between such probes are typically reduced by two orders of
      magnitude.

PMID- 15504683
TI  - The NMR multi-transmit phased array: a Cartesian feedback approach.
AB  - The use of Cartesian feedback is proposed to solve the problem of using an array
      of coils for the purposes of transmission in magnetic resonance imaging. The
      difficulties caused by direct and sample-mediated coil interactions are briefly
      examined, and the known solutions of using power-mismatched pre-amplifiers and
      transmitters noted. It is then shown that, without loss of transmitter
      efficiency, a high effective impedance may be created in series with each coil in
      the array by the use of Cartesian negative feedback. A bench experiment is
      described that confirms the theory. The solution is also viable for signal
      reception and is more efficacious than pre-amplifier damping, albeit over a
      smaller bandwidth.

PMID- 15504684
TI  - Investigating magnetically aligned phospholipid bilayers with EPR spectroscopy at
      Q-band (35 GHz): optimization and comparison with X-band (9 GHz).
AB  - This paper presents the improvement and advantages of investigating magnetically
      aligned phospholipid bilayers (bicelles) utilizing electron paramagnetic
      resonance (EPR) spectroscopy at a microwave frequency of 35 GHz (Q-band) and at a
      high magnetic field strength of 1.25 T when compared to weaker magnetic fields
      for X-band EPR studies. The nitroxide spin label 3beta-doxyl-5alpha-cholestane
      (cholestane or CLS) was inserted into the bicelles and utilized to demonstrate
      the effects of macroscopic bilayer alignment through the measurement of
      orientational dependent hyperfine splittings. The effects of different lanthanide
      ions with varying degree of magnetic susceptibility anisotropy were examined. The
      requirement of minimal amounts of the Tm3+ and Dy3+ lanthanide ions for well
      aligned bicelles were examined for Q-band and compared with amounts required for
      X-band bicelle alignment studies. At a magnetic field of 1.25 T (when compared to
      0.63 T at X-band), the perpendicular and parallel orientation were aligned with
      lower concentrations of Dy3+ and Tm3+, respectively, and thereby
      eliminating/minimizing the unwanted effects associated with lanthanide-protein
      interactions. Thus, it is much easier to magnetically align phospholipid bilayers
      at Q-band when compared to X-band.

PMID- 15504685
TI  - Absorption line CW EPR using an amplitude modulated longitudinal field.
AB  - In standard continuous wave electron paramagnetic resonance (CW-EPR) experiments,
      the first derivative of absorption lines is detected. This type of a line shape
      is caused by the magnetic field modulation and is usually an undesired feature,
      since the sensitivity of CW-EPR drastically decreases with increasing linewidth.
      A new approach is introduced, which allows for the measurement of absorption line
      EPR spectra in systems with broad inhomogeneous lines. The method makes use of
      multiple-photon transitions that are induced in spin systems when a transverse
      microwave and a longitudinal radio frequency field are simultaneously applied.
      The absorption lines are obtained by using amplitude modulation of the radio
      frequency field and slight saturation of the spectral lines. The basics of the
      new approach are discussed and experimental examples are given.

PMID- 15504686
TI  - Spatially selective T2 and T2 * measurement with line-scan echo-planar
      spectroscopic imaging.
AB  - Line-scan echo planar spectroscopic imaging (LSEPSI) is applied to quickly
      measure the T2 and T2* relaxation time constants in pre-selected 2D or 3D
      regions. Results from brain imaging studies at 3T suggest that the proposed
      method may prove valuable for both basic research (e.g., quantifying the changes
      of T2/T2* values in functional MRI with blood oxygenation level-dependent
      contrast) and clinical studies (e.g., measuring the T2' shortening due to iron
      deposition). The proposed spatially selective T2 and T2* mapping technique is
      especially well suited for studies, where T2/T2* quantification needs to be
      performed dynamically in a pre-selected 2D or 3D region.

PMID- 15504687
TI  - An algorithm to calculate the NMR signal of a multi spin-echo sequence with
      relaxation and spin-diffusion.
AB  - An algorithm to calculate NMR signals of a multi-echo pulse sequence with
      arbitrary position dependent B0 and B1 fields taking into account relaxation and
      spin-diffusion is presented. The multi-echo pulse sequence consists of an initial
      RF pulse ("90 degrees " RF pulse) and a series of L refocusing RF pulses with
      arbitrary phases and flip-angles. The calculation is exact and takes into account
      all the magnetization pathways that contribute to the signal on a predefined
      spatial grid. The theoretical prediction is verified experimentally using a high
      field NMR microscopy system. The algorithm was implemented in a simulation
      program in order to optimize the design of an inside-out MR intra-vascular
      catheter that is used for characterization of vessel wall tissue. Measured data
      obtained with the catheter are in good agreement with the theoretical prediction
      of the simulation.

PMID- 15504688
TI  - Short-time restricted diffusion in a static gradient and the attenuation of
      individual coherence pathways.
AB  - We experimentally explore some of the implications of a recent theoretical study
      [J. Magn. Reson. 64 (2003) 145] for the measurement of restricted diffusion in
      connected porous media in a static gradient. In particular, we examine how
      restriction affects the short-time attenuation of different coherence pathways,
      all excited with the same sequence of slice-selective radiofrequency (RF) pulses,
      and how the various pathways make the transition to the long-time or tortuosity
      regime. We confirm that every pathway contains equivalent diffusional information
      and, for short times, yields the surface-to-volume ratio (S/V) of the confining
      space. We find also, in agreement with the theoretical predictions, that
      different pathways are controlled by different time scales and, thus, exhibit
      different sensitivity to restriction. This property might be exploited when
      designing optimal sequences to study restricted motion.

PMID- 15504689
TI  - Development and application of rotationally compensated RARE.
AB  - In this paper we describe a new extension to the RARE rapid imaging technique-
      ROTACOR--which compensates for constant sample rotational motion by rotating the
      direction of the gradient coordinate system (read and phase directions) between
      each refocusing RF pulse and therefore between each acquisition of a line of k
      space in the read direction. In the laboratory frame this corresponds to an
      irregularly sampled k-space raster; for a sample rotating at the predefined
      rotation rate this will correspond to the sampling of a rectilinear k-space
      raster. This technique is applied to two rotating systems. First, to demonstrate
      the technique, a rotating mixing paddle in water is imaged using conventional
      RARE and then using the ROTACOR sequence, demonstrating the improvement of image
      quality produced by ROTACOR. Second, ROTACOR is used to image the deformation of
      water droplets in silicone oil, being sheared in a wide-gap Couette cell.
      Accurate imaging of the droplet shape as a function of shear rate, permits
      determination of the interfacial tension between the two fluids concerned; the
      results compare favourably with reported literature values.

PMID- 15504690
TI  - Velocity distributions remotely measured with a single-sided NMR sensor.
AB  - The pulsed field gradient nuclear magnetic resonance (PFG NMR) method has proved
      to be a powerful non-invasive technique to measure molecular displacement in
      various systems. It has been largely implemented with conventional NMR magnets
      where the volume for housing the flow setup is restricted. In this work we
      present the first approach to measure velocity distributions ex situ implementing
      a pulsed field gradient sequence on a single-sided NMR sensor. The open geometry
      of these sensors provides access to NMR measurements of a large number of
      applications previously excluded by the geometry of conventional closed magnets.
      Both, the distortions to the displacement encoding observed when implementing a
      PFG sequence in the presence of strongly inhomogeneous B0 and B1 fields, and the
      performance of the modifications proposed to eliminate these distortions are
      shown by means of numerical simulations. An alternating stimulated spin-echo PFG
      sequence implemented to remotely measure velocity distributions was combined with
      a multi-echo acquisition scheme to significantly increase the sensitivity of the
      method. The technique was implemented to measure the velocity propagator in a
      fluid undergoing laminar flow and good agreement with the theoretical result is
      observed.

PMID- 15504691
TI  - Spatially varying steady state longitudinal magnetization in distant dipolar
      field-based sequences.
AB  - Sequences based on the distant dipolar field (DDF) have shown great promise for
      novel spectroscopy and imaging. Unless spatial variation in the longitudinal
      magnetization, Mz(s), is eliminated by relaxation, diffusion, or spoiling
      techniques by the end of a single repetition, unexpected results can be obtained
      due to spatial harmonics in the steady state MzSS(s) profile. This is true even
      in a homogeneous single-component sample. We have developed an analytical
      expression for the MzSS(s) profile that occurs in DDF sequences when smearing by
      diffusion is negligible in the TR period. The expression has been verified by
      directly imaging the MzSS(s) profile after establishing the steady state.

PMID- 15504692
TI  - Modified z-gradient filtering as a mean to obtain phased deuterium
      autocorrelation 2D NMR spectra in oriented solvents.
AB  - We describe a modified z-gradient filter scheme specifically designed to obtain
      pure absorption mode deuterium 2D NMR spectra recorded in oriented solvents. The
      proposed technique is investigated by analysing the evolution of the density
      operator for a spin I=1. The method is applied to the recently designed Q-COSY
      and Q-resolved 2D experiments to simplify the analysis of chiral molecules
      dissolved in weakly orienting chiral liquid crystals. The efficiency of this z
      gradient filtering technique is illustrated using the perdeuterated 1-butanol, a
      prochiral molecule of average Cs symmetry, dissolved in an organic solution of
      poly-gamma-benzyl-L-glutamate (PBLG). The experimental results as well as the
      advantages of the new experiments compared with the previous ones are described
      and discussed.

PMID- 15504693
TI  - Water suppression without signal loss in HR-MAS 1H NMR of cells and tissues.
AB  - In cell and tissue samples, water is normally three orders of magnitude more
      abundant than other metabolites. Thus, water suppression is required in the
      acquisition of NMR spectra to overcome the dynamic range problem and to recover
      metabolites that overlap with the broad baseline of the strong water resonance.
      However, the heterogeneous cellular environment often complicates water
      suppression and the strong coupling of water to membrane lipids interferes with
      the NMR detection of membrane associated lipid components. The widely used water
      suppression techniques including presaturation and double pulsed field gradient
      selective echo result in more than a 70% reduction in membrane associated lipid
      components in proton spectra of cells and tissues compared to proton spectra
      acquired in the absence of water suppression. A water suppression technique based
      on the combination of selective excitation pulses and pulsed field gradients is
      proposed to use in the acquisition of high resolution MAS NMR spectra of tissue
      specimens and cell samples. This pulse sequence methodology enables efficient
      water suppression for intact cells and tissue samples and eliminates signal loss
      from cellular metabolites.

PMID- 15504694
TI  - Noise properties of a NMR transceiver coil array.
AB  - The use of multiple radiofrequency (RF) surface coil elements has applications in
      both fast parallel imaging and conventional imaging techniques. Through
      implementation of a simple magnetic decoupling network, 50 Omega matching can be
      achieved in both the transmitter and receiver chains, enabling the use of
      conventional RF power amplifiers and preamplifiers for transceive applications.
      Unlike phased array coil arrangements using low impedance preamplifiers for
      decoupling, the noise correlation between 50 Omega coils decoupled with discrete
      components has not been characterized. We have measured the dependence of coil
      quality factor (Q-factor) and noise correlation on coil separation and shown
      these quantities to be consistent with theoretical arguments, at least at 4 T
      (170 MHz). Our results suggest that a coil system for transmission and reception
      of NMR signals with 50 Omega coils can be built to take advantage of all the
      benefits of conventional array coils and with the added advantages of using
      conventional amplifiers.

PMID- 15504695
TI  - Magnetic resonance imaging of single rice kernels during cooking.
AB  - The RARE imaging method was used to monitor the cooking of single rice kernels in
      real time and with high spatial resolution in three dimensions. The imaging
      sequence is optimized for rapid acquisition of signals with short relaxation
      times using centered out RARE. Short scan time and high spatial resolution are
      critical factors in the investigation of the cooking behavior of rice kernels
      since time and spatial averaging may lead to erroneous results. The results are
      confirming the general pattern of moisture ingress that has been suspected from
      previous (more limited) studies. Water uptake as determined by analysis of the
      MRI time series recorded during cooking compares well with gravimetric studies.
      This allows using these real-time MRI data for developing and validating models
      that describe the effect of kernel microstructure on its cooking behavior.

PMID- 15504696
TI  - Ultrafast 2D NMR spectroscopy using a continuous spatial encoding of the spin
      interactions.
AB  - A new protocol for acquiring multidimensional NMR spectra within a single scan is
      introduced and illustrated. The approach relies on applying a pair of frequency
      chirped excitation and storage pulses in combination with echoing magnetic field
      gradients, in order to impart the kind of linear spatial encoding of the NMR
      interactions that is required by ultrafast 2D NMR spectroscopy. It is found that
      when dealing with 2D NMR experiments involving a t1 amplitude-modulation of the
      spin evolution, such continuous encoding scheme presents a number of advantages
      over alternatives employing discrete excitation pulses. From an experimental
      standpoint this is mainly reflected by the use of a single pair of bipolar
      gradients during the course of the indirect-domain encoding, as opposed to the
      numerous (and more intense) gradient echoes required so far. In terms of the
      spectral outcome, main advantages of the continuous spatial encoding scheme are
      the avoidance of "ghost peaks" and of "enveloping effects" associated to the
      discrete excitation mode. The principles underlying this new spatial encoding
      protocol are derived, and its applicability is demonstrated with homo- and
      heteronuclear 2D ultrafast NMR applications on small molecule and on protein
      samples.

PMID- 15504697
TI  - Uniform illumination of optically dense NMR samples.
AB  - We demonstrate a simple, inexpensive method for in situ laser illumination of NMR
      samples using a stepwise tapered optical fibre to deliver light uniformly along
      the axis of a 5 mm NMR tube. The optical path length of the incident light inside
      the sample is about 3 mm, allowing efficient illumination of optically dense
      samples. The degradation in spectral resolution and the reduction in filling
      factor are both minimal. Probe modifications are not required.

PMID- 15504698
TI  - Simulation of 13C nuclear magnetic resonance spectra of lignin compounds using
      principal component analysis and artificial neural networks.
AB  - Theoretical models relating atom-based structural descriptors to 13C NMR chemical
      shifts were used to accurately simulate 13C NMR spectra of lignin model compounds
      (poly-substituted phenols). The structure-activity relationship (SAR) studies for
      15 lignins using pattern recognition methods of principal component analysis
      (PCA) and artificial neural networks (ANNs) were performed in this work. The most
      important parameters affecting the 13C chemical shifts of different carbons were
      descriptors consisting of the charge density of the atoms at different distances
      from the center carbon. Among the large number of parameters, these descriptors
      were selected using PCA and were used as ANN input. The least square regression
      analyses of the results indicate correlation coefficient (R) values in excess of
      0.983 for the total data set.

PMID- 15504699
TI  - The DQ-HN[CACB] and DQ-HN(CO)[CACB] sequences with evolution of double quantum
      Calpha-Cbeta coherences.
AB  - The new variant of known HNCACB and HN(CO)CACB techniques is proposed that
      employs excitation and evolution of double quantum Calpha-Cbeta coherences. The
      most important features of the new method are: increased signal dispersion, lack
      of splittings due to 1J(Calpha-Cbeta) spin-spin couplings, and absence of
      accidental cancellations of positive and negative signals. The acquisition of
      both DQ-HN[CACB] and DQ-HN(CO)[CACB] techniques enables sequential assignment of
      protein backbone, using only Calpha-Cbeta DQ-frequencies. The determination of
      all Calpha and Cbeta chemical shifts requires, however, a comparison with
      HN(CO)CA or HNCA spectra. Examples of applications of the DQ-HN[CACB] and DQ
      HN(CO)[CACB] experiments are presented, employing the 2D Reduced Dimensionality
      approach for 13C, 15N-labeled ubiquitin, and the 3D acquisition for 13C, 15N
      double labeled Ca2+ -binding bovine S100A1 protein in the apo state (21 kDa) with
      overall correlation time of 8.1 ns.

PMID- 15504701
TI  - Rapid translation system: a novel cell-free way from gene to protein.
AB  - Proteome research has recently been stimulated by important technological
      advances in the field of recombinant protein expression. One major breakthrough
      was the development of a new generation of cell-free transcription/translation
      systems. The open and flexible character of these systems allows direct control
      over expression conditions via the addition of supplements to the expression
      reaction. The possibility of working with linear expression templates instead of
      cloned plasmids and the ease of downstream processing, circumventing the need for
      cell-lysis, makes them ideally suited for high-throughput screening applications.
      Among these novel cell-free systems, the Rapid Translation System (RTS) developed
      by Roche is the first one that is scalable from micrograms to milligrams of
      protein. This review describes the basic principles of RTS which differentiate it
      from traditional in vitro expression technologies, starting from template
      generation to high-end applications like labeling for structural biology
      research. Recent results obtained by RTS users from different institutions are
      presented to illustrate each step of a novel cell-free protein expression
      workflow and its benefits compared to traditional cell-based expression.

PMID- 15504702
TI  - Protein expression and refolding--a practical guide to getting the most out of
      inclusion bodies.
AB  - The release of sequence data, particularly from a number of medically and
      biotechnologically important genomes, is increasing in an exponential fashion. In
      light of this, elucidating the structure and function of proteins, particularly
      in a "high throughput" manner, is an important quest. The production of
      recombinant proteins however is not always straightforward, with a number of
      proteins falling prey to low expression problems, a high susceptibility to
      proteolysis and the often despised production of inclusion bodies. Whilst
      expression as inclusion bodies can often be advantageous, their solubilization
      and renaturation is often a time consuming and empirical process. In this review,
      we aim to outline some of the more common approaches that have been applied to a
      variety of proteins and address issues associated with their handling.

PMID- 15504703
TI  - Towards a systems biology understanding of human health: interplay between
      genotype, environment and nutrition.
AB  - Sequencing of the human genome has opened the door to the most exciting new era
      for the holistic system description of human health. It is now possible to study
      the underlying mechanisms of human health in relation to diet and other
      environmental factors such as drugs and toxic pollutants. Technological advances
      make it feasible to envisage that in the future personalized drug treatment and
      dietary advice and possibly tailored food products can be used for promoting
      optimal health on an individual basis, in relation to genotype and lifestyle.
      Life-Science research has in the past very much focused on diseases and how to
      reestablish human health after illness. Today, the role of food and nutrition in
      human health and especially prevention of illness is gaining recognition.
      Diseases of modern civilization, such as diabetes, heart disease and cancer have
      been shown to be effected by dietary patterns. The risk of disease is often
      associated with genetic polymorphisms, but the effect is dependent on dietary
      intake and nutritional status. To understand the link between diet and health,
      nutritional-research must cover a broad range of areas, from the molecular level
      to whole body studies. Therefore it provides an excellent example of integrative
      biology requiring a systems biology approach. The current state and implications
      of systems biology in the understanding of human health are reviewed. It becomes
      clear that a complete mechanistic description of the human organism is not yet
      possible. However, recent advances in systems biology provide a trajectory for
      future research in order to improve health of individuals and populations.
      Disease prevention through personalized nutrition will become more important as
      the obvious avenue of research in life sciences and more focus will need to be
      put upon those natural ways of disease prevention. In particular, the new
      discipline of nutrigenomics, which investigates how nutrients interact with
      humans, taking predetermined genetic factors into account, will mediate new
      insights into human health that will finally have significant positive impact on
      our quality of life.

PMID- 15504704
TI  - Public health issues related with the consumption of food obtained from
      genetically modified organisms.
AB  - Genetically Modified Organisms (GMOs) are a fact of modern agriculture and a
      major field of discussion in biotechnology. As science incessantly achieves
      innovative and unexpected breakthroughs, new medical, political, ethical and
      religious debates arise over the production and consumption of transgenic
      organisms. Despite no described medical condition being directly associated with
      a diet including approved GM crops in large exposed populations such as
      300,000,000 Americans and a billion Chinese, public opinion seems to look at this
      new technology with either growing concern or even disapproval. It is generally
      recognized that a high level of vigilance is necessary and highly desirable, but
      it should also be considered that GMOs are a promising new challenge for the III
      Millennium societies, with remarkable impact on many disciplines and fields
      related to biotechnology. To acquire a basic knowledge on GMO production, GM-food
      consumption, GMO interaction with humans and environment is of primary importance
      for risk assessment. It requires availability of clear data and results from
      rigorous experiments. This review will focus on public health risks related with
      a GMO-containing diet. The objective is to summarize state of the art research,
      provide fundamental technical information, point out problems and perspectives,
      and make available essential tools for further research. Are GMO based industries
      and GMO-derived foods safe to human health? Can we consider both social, ethical
      and public health issues by means of a constant and effective monitoring of the
      food chain and by a clear, informative labeling of the products? Which are the so
      far characterized or alleged hazards of GMOs? And, most importantly, are these
      hazards actual, potential or merely contrived? Several questions remain open;
      answers and solutions belong to science, to politics and to the personal opinion
      of each social subject.

PMID- 15504705
TI  - p75 neurotrophin receptor signaling in the nervous system.
AB  - The neurotrophin receptor p75(NTR) has long been known as a receptor for
      neurotrophins that promote survival and differentiation. Consistent with the role
      of neurotrophins, p75(NTR) is expressed during the developmental stages of the
      nervous system. However, p75(NTR) is re-expressed in various pathological
      conditions in the adult. We now know that p75(NTR) has the ability to elicit bi
      directional signals, that result in the inhibition as well as the promotion of
      the neurite outgrowth. p75(NTR) is a key receptor for myelin-derived inhibitory
      cues that contribute to the lack of regeneration of the central nervous system.

PMID- 15504706
TI  - Phage display for epitope determination: a paradigm for identifying receptor
      ligand interactions.
AB  - Antibodies that react with many different molecular species of protein and non
      protein nature are widely studied in biology and have particular utilities, but
      the precise epitopes recognized are seldom well defined. The definition of
      epitopes by X-ray crystallography of the antigen-antibody complex, the gold
      standard procedure, has shown that most antibody epitopes are conformational and
      specified by interactions with topographic determinants on the surface of the
      antigenic molecule. Techniques available for the definition of such epitopes are
      limited. Phage display using either gene-specific libraries, or random peptide
      libraries, provides a powerful technique for an approach to epitope
      identification. The technique can identify amino acids on protein antigens that
      are critical for antibody binding and, further, the isolation of peptide motifs
      that are both structural and functional mimotopes of both protein and non-protein
      antigens. This review discusses techniques used to isolate such mimotopes, to
      confirm their specificity, and to characterize peptide epitopes. Moreover there
      are direct practical applications to deriving epitopes or mimotopes by sequence,
      notably the development of new diagnostic reagents, or therapeutic agonist or
      antagonist molecules. The techniques developed for mapping of antibody epitopes
      are applicable to probing the origins of autoimmune diseases and certain cancers
      by identifying "immunofootprints" of unknown initiating agents, as we discuss
      herein, and are directly applicable to examination of a wider range of receptor
      ligand interactions.

PMID- 15504707
TI  - DNA vaccines and their application against parasites--promise, limitations and
      potential solutions.
AB  - DNA or nucleic acid vaccines are being evaluated for efficacy against a range of
      parasitic diseases. Data from studies in rodent model systems have provided proof
      of principle that DNA vaccines are effective at inducing both humoral and T cell
      responses to a variety of candidate vaccine antigens. In particular, the
      induction of potent cellular responses often gives DNA vaccination an
      immunological advantage over subunit protein vaccination. Protection against
      parasite challenge has been demonstrated in a number of systems. However,
      application of parasite DNA vaccines in large animals including ruminants,
      primates and humans has been compromised by the relative lack of immune
      responsiveness to the vaccines, but the reasons for this hyporesponsiveness are
      not clear. Here, we review DNA vaccines against protozoan parasites, in
      particular vaccines for malaria, and the use of genomic approaches such as
      expression library immunization to generate novel vaccines. The application of
      DNA vaccines in ruminants is reviewed. We discuss some of the approaches being
      evaluated to improve responsiveness in large animals including the use of
      cytokines as adjuvants, targeting molecules as delivery ligands, electroporation
      and CpG oligonucleotides.

PMID- 15504708
TI  - Drug-induced and antibody-mediated pure red cell aplasia: a review of literature
      and current knowledge.
AB  - Anti-erythropoietin (EPO)-induced pure red cell aplasia (PRCA) is an uncommon,
      potentially life-threatening condition in which the bone marrow stops
      manufacturing red blood cells. In the past few years, reports of drug-induced,
      anti-EPO antibody-mediated PRCA have increased substantially, with most cases
      attributed to the use of one erythropoiesis-stimulating protein, Eprex. A
      literature review was undertaken to document the reports of drug-induced PRCA,
      with all drugs and drug regimens. The sudden increase in reports of antibody
      mediated PRCA is discussed.

PMID- 15504709
TI  - Using the biologic license application or new drug application as a basis for the
      common technical document.
AB  - With the introduction of the common technical document (CTD), many writers in the
      biotech and pharmaceutical industries are now required to submit dossiers in this
      format. The format of the CTD is not extremely difficult from the familiar
      documents of the Biologic License Application (BLA) or New Drug Application
      (NDA). The CTD can be mapped to existing areas of the BLA or NDA. The components
      of the CTD are discussed and references to the current guidance worldwide are
      provided to assist the writer.

PMID- 15504710
TI  - Guidelines and policies for medical writers in the biotech industry: an update on
      the controversy.
AB  - Papers reporting the results of clinical trials written by medical writers
      employed by the biotech and pharmaceutical industries have been criticized for
      possible bias in presentation and failure to adhere to authorship guidelines.
      Several groups have attempted to address the concerns of journal editors,
      academics, regulators, and the general public by issuing guidelines and policies
      for the preparation of such material.

PMID- 15504711
TI  - Radioimmunotherapy of non-Hodgkin's lymphoma: clinical development of the Zevalin
      regimen.
AB  - Zevalin (ibritumomab tiuxetan; IDEC Pharmaceuticals Corporation, San Diego, CA,
      USA) was approved by the United States Food and Drug Administration on February
      19, 2002, following 9 years of clinical development. Six clinical studies
      supported the Zevalin Biologics License Application. The Zevalin regimen is
      indicated for the treatment of patients with relapsed or refractory low-grade,
      follicular, or transformed B-cell non-Hodgkin's lymphoma (NHL), and for those
      with follicular NHL refractory to Rituxan (rituximab, MabThera; IDEC
      Pharmaceuticals Corporation, San Diego, CA and Genentech, South San Francisco,
      CA). In the year following FDA approval, approximately 1300 patients were treated
      in clinical trials or with the commercially available product.

PMID- 15504712
TI  - Biosimulation software is changing research.
AB  - Biosimulation software is being used in pharmaceutical drug development to mimic
      diseases. Virtual clinical trials of new developing pharmaceutical drugs can be
      conducted on computers running disease simulations. Using virtual patients
      instead of clinical research patients can save both time and money for
      pharmaceutical companies in their search to discover new drugs and bring them to
      market. In the future, this type of research will be commonplace.

PMID- 15504713
TI  - An unusual case of neurocutaneous melanosis.
AB  - The neurocutaneous melanosis (NCM) is a rare, neuroectodermal dysplasia defined
      by the association of giant or multiple, nonmalignant pigmented cutaneous nevi
      with leptomeningeal melanosis or melanoma. As a rule, the cerebral pathological
      substratum is characterized by a melanocytic infiltration of the leptomeninges,
      often leading to hydrocephalus. The most frequent clinical symptomatology starts
      early in life, with convulsive seizures, psychomotor delay, intracranial
      hyperpression: the prognosis is severe. Malignant melanomas can also occur. One
      21 years-old patient affected by NCM with a giant bathing nevus and epilepsy is
      reported. Her psychomotor development was slightly delayed. Academic progress was
      disturbed by the frequency of seizures and the multiple dermatological surgeries,
      and she remained at the elementary school level. Her epilepsy appeared at seven
      years and became pharmacoresistant. It was a focal, left temporal epilepsy.
      Neuroimaging investigations were performed repeatedly, and demonstrated the
      progressive appearance of parenchymal lesions with T1 and T2 shortening, without
      contrast enhancement, at the pons (11 years), the two hippocampi (14 years), and
      of an atrophy of the cerebellum and the brainstem (19 years). No hydrocephalus,
      tumoral aspect, or meningeal involvement were demonstrated. This patient's case
      is peculiar because her neurological symptomatology consists only of focal
      epilepsy, unrelated to a tumor, with moderate cognitive impairment despite a
      rather long course of the disease. Her evolution raises the question of
      condidency to surgical treatment.

PMID- 15504714
TI  - Adverse motor effects induced by antiepileptic drugs.
AB  - Cognitive effects of anti-epileptic drugs (AEDs) have been already extensively
      reported. In contrast, motor disturbances, frequently induced by these drugs,
      have not received similar attention. We review subjective and objective adverse
      motor effects of traditional and new AEDs. We discuss the methodological issues
      caused by the heterogeneous sources of information on drug adverse effects
      (controlled clinical studies, open studies, and case reports). We describe
      specific disturbances (vestibulocerebellar, dyskinesias, parkinsonism, tics,
      myoclonus, and tremor) as the effects of different AEDs on distinct motor
      circuitries. Finally, we summarize the role of sophisticated technical studies
      which provide a valuable insight into the specific or subtle effects of AEDs on
      the central nervous system.

PMID- 15504715
TI  - Late onset hyperekplexia.
AB  - We report on the case of an 86-year-old woman who rapidly became unable to stand
      and walk because of jerky movements, suggesting a clinical diagnosis of
      myoclonus. It was observed that both unexpected and expected stimuli (audiogenic,
      tactile, or visual) triggered the myoclonic jerks. Electrophysiological
      exploration, including a coupled EEG-EMG study, showed the occurrence of a
      patterned motor response to each stimulation (whatever the modality), consisting
      of eye blinking, head flexion, abduction of the upper arms, movement of the
      trunk, and bending of the knees. Given the absence of any relevant past history
      and lack of biological or neurological abnormalities including on CT scan brain
      imaging, the diagnosis of late-onset hyperekplexia was suggested. Substantial
      abatement of the clinical symptomatology was obtained after introduction of low
      dose clonazepam.

PMID- 15504716
TI  - The roles of electroencephalography and neuroimaging in children with
      holoprosencephaly.
AB  - We analyze the respective roles of neuro-imaging and EEG in the assessment of 11
      children with holoprosencephaly and epilepsy. Seizures were present in seven
      patients (64%); six were treated with antiepileptic drugs; five had intractable
      epilepsy. Two of the patients with intractable epilepsy became seizure-free under
      polytherapy. Fourteen EEG recordings were performed in eight patients. The
      abnormal EEG findings included slow waves, focal epileptiform discharges, slow
      spike-and-wave complexes, hypsarrhythmia, frontal fast activity, fronto-occipital
      gradients of amplitudes (posterior amplitude attenuation), lack of photic
      driving, periodic discharges, and extremely large amplitudes. A fronto-occipital
      gradient was found only in alobar and semilobar holoprosencephaly (HPE), while
      hypsarrhythmia only in lobar HPE. Lack of photic driving was found only in alobar
      HPE. All EEGs showed diffuse slow waves, and all patients had severe
      developmental delay. The Deep Gray Score(DGS) in neuroimaging studies, thought to
      predict clinical outcome, was irrelevant given the presence and intractability of
      the epilepsies. Patients with higher DGS, nonetheless, tended to have higher
      mortality rate. In conclusion, EEG evaluation provides additional functional
      information to neuroimaging studies in the assessment of neurological outcome in
      patients with HPE. With a more mature and well-formed cerebrum, as found in the
      lobar and semilobar types, the possibility of hypsarrhythmia and photic driving
      increased, while that of fronto-occipital gradients decreased.

PMID- 15504717
TI  - Stuttering or reflex seizure? A case report.
AB  - Stuttering is characterized by involuntary syllabic repetitions and interruption
      in the smooth flow of speech. The exact cause of primary stuttering remains a
      matter of debate but a frontal dysfunction has been evoked. On the other hand,
      acquired stuttering is uncommon. We report a case of reflex epilepsy in which
      seizures were triggered by reading aloud or stressful conversation. Each
      paroxysmal event in left frontal region was associated clinically with a language
      disorder mimicking stuttering. Our observation suggests that reflex frontal focal
      epilepsy could be a putative etiology for acquired stuttering.

PMID- 15504719
TI  - Effect of caldesmon on the position and myosin-induced movement of smooth muscle
      tropomyosin bound to actin.
AB  - It is known that the actin-binding protein caldesmon inhibits actomyosin ATPase
      activity and might in this way take part in the thin filament regulation of
      smooth muscle contraction. Although the molecular mechanism of this inhibition is
      unknown, it is clear that the presence of actin-bound tropomyosin is necessary
      for full inhibition. Recent evidence also suggests that the myosin-induced
      movement of tropomyosin plays a key role in regulation. In this work,
      fluorescence studies provide evidence to show that caldesmon interacts with and
      alters the position of tropomyosin in a reconstituted actin thin filament and
      thereby limits the ability of myosin heads to move tropomyosin. Caldesmon
      interacts with the Cys-190 region in the COOH-terminal half of tropomyosin,
      resulting in the movement of this part of tropomyosin to a new position on actin.
      Additionally, this constrains the myosin-induced movement of this region of
      tropomyosin. On the other hand, caldesmon does not appear to interact with the
      Cys-36 region in the NH2-terminal half of tropomyosin and neither alters the
      position of nor significantly constrains the myosin-induced movement of this part
      of tropomyosin. The ability of caldesmon to limit the myosin-induced movement of
      tropomyosin provides a possible molecular basis for the inhibitory function of
      caldesmon. The different movements of the two halves of tropomyosin indicate that
      actin-bound tropomyosin moves as a flexible molecule and not as a rigid rod.
      Interestingly, caldesmon, which inhibits tropomyosin's potentiation of actomyosin
      ATPase activity, moves tropomyosin in one direction, whereas myosin heads, which
      enhance potentiation, move tropomyosin in the opposite direction.

PMID- 15504720
TI  - Dynein light chain 1 phosphorylation controls macropinocytosis.
AB  - Recent studies have identified dynein light chain-1 (DLC1), a component of the
      dynein motor, as a p21-activated kinase 1 (Pak1)-interacting substrate with
      binding sites mapped to amino acids 61-89 of DLC1 and phosphorylation site at
      serine 88. Here we investigated the role of DLC1 phosphorylation by Pak1 upon the
      process of macropinocytosis. We found that Pak1 associates with dynein motor and
      that Pak1-DLC1 interaction starts at the initiation of pinosome formation and
      persists in early and late endosomes. Pak1 phosphorylation of DLC1 on Ser-88
      controls vesicle formation and trafficking functions, as Ser-88 substitution for
      alanine prevents macropinocytosis. A peptide spanning the C-terminal 19-amino
      acid region of DLC1 efficiently blocked Ser-88 phosphorylation and
      macropinocytosis. These results suggest that the regulation of DLC1 by Pak1 is a
      novel mechanism by which a signaling kinase might influence macropinocytosis.

PMID- 15504721
TI  - Direct comparison of the functional roles played by different transmembrane
      regions in the cystic fibrosis transmembrane conductance regulator chloride
      channel pore.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel
      contains 12 transmembrane (TM) regions that are presumed to form the channel
      pore. However, little is known about the relative functional contribution of
      different TM regions to the pore. We have used patch clamp recording to
      investigate the functional consequences of point mutations throughout the six
      transmembrane regions in the N-terminal part of the CFTR protein (TM1-TM6). A
      range of specific functional assays compared the single channel conductance,
      anion binding, and anion selectivity properties of different channel variants.
      Overall, our results suggest that TM1 and -6 play dominant roles in forming the
      channel pore and determining its functional properties, with TM5 perhaps playing
      a lesser role. In contrast, TM2, -3, and -4 appear to play only minor supporting
      roles. These results define transmembrane regions 1 and 6 as major contributors
      to the CFTR channel pore and have strong implications for emerging structural
      models of CFTR and related ATP-binding cassette proteins.

PMID- 15504723
TI  - Direct evidence that neural cell adhesion molecule (NCAM) polysialylation
      increases intermembrane repulsion and abrogates adhesion.
AB  - Molecular force measurements quantified the impact of polysialylation on the
      adhesive properties both of membrane-bound neural cell adhesion molecule (NCAM)
      and of other proteins on the same membrane. These results show quantitatively
      that NCAM polysialylation increases the range and magnitude of intermembrane
      repulsion. The repulsion is sufficient to overwhelm both homophilic NCAM and
      cadherin attraction at physiological ionic strength, and it abrogates the protein
      mediated intermembrane adhesion. The steric repulsion is ionic strength dependent
      and decreases substantially at high monovalent salt concentrations with a
      concomitant increase in the intermembrane attraction. The magnitude of the
      repulsion also depends on the amount of polysialic acid (PSA) on the membranes,
      and the PSA-dependent attenuation of cadherin adhesion increases with increasing
      PSA-NCAM:cadherin ratios. These findings agree qualitatively with independent
      reports based on cell adhesion studies and reveal the likely molecular mechanism
      by which NCAM polysialylation regulates cell adhesion and intermembrane space.

PMID- 15504722
TI  - Evaluation of the 17-kDa prenyl-binding protein as a regulatory protein for
      phototransduction in retinal photoreceptors.
AB  - The mammalian rod photoreceptor phosphodiesterase (PDE6) holoenzyme is isolated
      in both a membrane-associated and a soluble form. Membrane binding is a
      consequence of prenylation of PDE6 catalytic subunits, whereas soluble PDE6 is
      purified with a 17-kDa prenyl-binding protein (PDEdelta) tightly bound. This
      protein, here termed PrBP/delta, has been hypothesized to reduce activation of
      PDE6 by transducin, thereby desensitizing the photoresponse. To test the
      potential role of PrBP/delta in regulating phototransduction, we examined the
      abundance, localization, and potential binding partners of PrBP/delta in retina
      and in purified rod outer segment (ROS) suspensions whose physiological and
      biochemical properties are well characterized. The amphibian homologue of
      PrBP/delta was cloned and sequenced and found to have 82% amino acid sequence
      identity with mammalian PrBP/delta. In contrast to bovine ROS, all of the PDE6 in
      purified frog ROS is membrane-associated. However, addition of recombinant frog
      PrBP/delta can solubilize PDE6 and prevent its activation by transducin.
      PrBP/delta also binds other prenylated photoreceptor proteins in vitro, including
      opsin kinase (GRK1/GRK7) and rab8. Quantitative immunoblot analysis of the
      PrBP/delta content of purified ROS reveals insufficient amounts of PrBP/delta
      (<0.1 PrBP/delta per PDE6) to serve as a subunit of PDE6 in either mammalian or
      amphibian photoreceptors. The immunolocalization of PrBP/delta in frog and bovine
      retina shows greatest PrBP/delta immunolabeling outside the photoreceptor cell
      layer. Within photoreceptors, only the inner segments of frog double cones are
      strongly labeled, whereas bovine photoreceptors reveal more PrBP/delta labeling
      near the junction of the inner and outer segments (connecting cilium) of
      photoreceptors. Together, these results rule out PrBP/delta as a PDE6 subunit and
      implicate PrBP/delta in the transport and membrane targeting of prenylated
      proteins (including PDE6) from their site of synthesis in the inner segment to
      their final destination in the outer segment of rods and cones.

PMID- 15504724
TI  - Rpn4 is a physiological substrate of the Ubr2 ubiquitin ligase.
AB  - The homeostatic abundance of the proteasome in Saccharomyces cerevisiae is
      controlled by a feedback circuit in which transcriptional activator Rpn4 up
      regulates the proteasome genes and is destroyed by the assembled, active
      proteasome. Remarkably, the degradation of Rpn4 can be mediated by two
      independent pathways. One pathway is independent of ubiquitin, whereas the other
      involves ubiquitination on internal lysines. In the present study, we
      investigated the mechanism underlying the ubiquitin-dependent degradation of
      Rpn4. We demonstrated, through in vivo and in vitro assays, that Rpn4 is a
      physiological substrate of the Ubr2 ubiquitin ligase, which was originally
      identified as a sequence homolog of Ubr1, the E3 component of the N-end rule
      pathway. The ubiquitin-conjugating enzyme Rad6, which directly interacts with
      Ubr2, is also required for the ubiquitin-dependent degradation of Rpn4.
      Furthermore, we showed that deletion of UBR2 exhibited a strong synthetic growth
      defect with a mutation in the Rpt1 proteasome subunit when Rpn4 was
      overexpressed. This study not only identified the ubiquitination apparatus for
      Rpn4 but also unveiled the first physiological substrate of Ubr2. The biological
      significance of Ubr2-mediated degradation of Rpn4 is also discussed.

PMID- 15504725
TI  - Ric-3 promotes functional expression of the nicotinic acetylcholine receptor
      alpha7 subunit in mammalian cells.
AB  - Expression of functional, recombinant alpha7 nicotinic acetylcholine receptors in
      several mammalian cell types, including HEK293 cells, has been problematic. We
      have isolated the recently described human ric-3 cDNA and co-expressed it in
      Xenopus oocytes and HEK293 cells with the human nicotinic acetylcholine receptor
      alpha7 subunit. In addition to confirming the previously reported effect on
      alpha7 receptor expression in Xenopus oocytes we demonstrate that ric-3 promotes
      the formation of functional alpha7 receptors in mammalian cells, as determined by
      whole cell patch clamp recording and surface alpha-bungarotoxin binding. Upon
      application of 1 mm nicotine, currents were undetectable in HEK293 cells
      expressing only the alpha7 subunit. In contrast, co-expression of alpha7 and ric
      3 cDNAs resulted in currents that averaged 42 pA/pF with kinetics similar to
      those observed in cells expressing endogenous alpha7 receptors.
      Immunoprecipitation studies demonstrate that alpha7 and ric-3 proteins co
      associate. Additionally, cell surface labeling with biotin revealed the presence
      of alpha7 protein on the plasma membrane of cells lacking ric-3, but surface
      alpha-bungarotoxin staining was only observed in cells co-expressing ric-3. Thus,
      ric-3 appears to be necessary for proper folding and/or assembly of alpha7
      receptors in HEK293 cells.

PMID- 15504726
TI  - NO reduction by nitric-oxide reductase from denitrifying bacterium Pseudomonas
      aeruginosa: characterization of reaction intermediates that appear in the single
      turnover cycle.
AB  - Nitric-oxide reductase (NOR) of a denitrifying bacterium catalyzes NO reduction
      to N(2)O at the binuclear catalytic center consisting of high spin heme b(3) and
      non-heme Fe(B). The structures of the reaction intermediates in the single
      turnover of the NO reduction by NOR from Pseudomonas aeruginosa were investigated
      using optical absorption and EPR spectroscopies combined with an originally
      designed freeze-quench device. In the EPR spectrum of the sample, in which the
      fully reduced NOR was mixed with an NO solution and quenched at 0.5 ms after the
      mixing, two characteristic signals for the ferrous Fe(B)-NO and the penta
      coordinated ferrous heme b(3)-NO species were observed. The CO inhibition of its
      formation indicated that two NO molecules were simultaneously distributed into
      the two irons of the same binuclear center of the enzyme in this state. The time-
      and temperature-dependent EPR spectral changes indicated that the species that
      appeared at 0.5 ms is a transient reaction intermediate prior to the N(2)O
      formation, in good agreement with the so-called "trans" mechanism. It was also
      found that the final state of the enzyme in the single turnover cycle is the
      fully oxidized state, in which the mu-oxo-bridged ligand is absent between the
      two irons of its binuclear center, unlike the resting form of NOR as isolated. On
      the basis of these present findings, we propose a newly developed mechanism for
      the NO reduction reaction conducted by NOR.

PMID- 15504727
TI  - Synthesis of adenylated molybdopterin: an essential step for molybdenum
      insertion.
AB  - The molybdenum cofactor (Moco) is part of the active site of all molybdenum (Mo)
      dependent enzymes, except nitrogenase. Moco consists of molybdopterin (MPT), a
      phosphorylated pyranopterin with an enedithiolate coordinating Mo and it is
      synthesized by an evolutionary old multistep pathway. The plant protein Cnx1 from
      Arabidopsis thaliana catalyzes with its two domains (E and G) the terminal step
      of Moco biosynthesis, the insertion of Mo into MPT. Recently, the high-resolution
      MPT-bound structure of the Cnx1 G domain (Cnx1G) has been determined (Kuper, J.,
      Llamas, A., Hecht, H. J., Mendel, R. R., and Schwarz, G. (2004) Nature 430, 803
      806). Besides defining the MPT-binding site a novel and unexpected modification
      of MPT has been identified, adenylated MPT. Here we demonstrate that it is Cnx1G
      that catalyzes the adenylation of MPT. In vitro synthesized MPT was
      quantitatively transferred from Escherichia coli MPT synthase to Cnx1G. The
      subsequent adenylation reaction by Cnx1G was Mg(2+)- and ATP-dependent. Whereas
      Mn(2+) could partially replace Mg(2+), ATP was the only nucleotide accepted by
      Cnx1G. Consequently the formation of pyrophosphate was demonstrated, which was
      dependent on the ability of Cnx1G to bind MPT. Pyrophosphate, either formed in
      the reaction or added externally, inhibited the Cnx1G-catalyzed MPT adenylation
      reaction. Catalytically inactive Cnx1G mutant variants showed impaired MPT
      adenylation confirming that MPT-AMP is the reaction product of Cnx1G. Therefore
      Cnx1G is a MPT adenylyltransferase catalyzing the activation of MPT, a universal
      reaction in the Moco synthetic pathway because Cnx1G is able to reconstitute also
      bacterial and mammalian Moco biosynthesis.

PMID- 15504728
TI  - Determination of the functional unit of the cystic fibrosis transmembrane
      conductance regulator chloride channel. One polypeptide forms one pore.
AB  - The magnitudes and distributions of subconductance states were studied in
      chloride channels formed by the wild-type cystic fibrosis transmembrane
      conductance regulator (CFTR) and in CFTRs bearing amino acid substitutions in
      transmembrane segment 6. Within an open burst, it was possible to distinguish
      three distinct conductance states referred to as the full conductance,
      subconductance 1, and subconductance 2 states. Amino acid substitutions in
      transmembrane segment 6 altered the duration and probability of occurrence of
      these subconductance states but did not greatly alter their relative amplitudes.
      Results from real time measurements indicated that covalent modification of
      single R334C-CFTR channels by [2-(trimethylammonium)ethyl]methanethiosulfonate
      resulted in the simultaneous modification of all three conductance levels in what
      appeared to be a single step, without changing the proportion of time spent in
      each state. This behavior suggests that at least a portion of the conduction path
      is common to all three conducting states. The time course for the modification of
      R334C-CFTR, measured in outside-out macropatches using a rapid perfusion system,
      was also consistent with a single modification step as if each pore contained
      only a single copy of the cysteine at position 334. These results are consistent
      with a model for the CFTR conduction pathway in which a single anion-conducting
      pore is formed by a single CFTR polypeptide.

PMID- 15504729
TI  - Loss of caveolin-1 polarity impedes endothelial cell polarization and directional
      movement.
AB  - The ability of a cell to move requires the asymmetrical organization of cellular
      activities. To investigate polarized cellular activity in moving endothelial
      cells, human endothelial cells were incubated in a Dunn chamber to allow
      migration toward vascular endothelial growth factor. Immunofluorescent staining
      with a specific antibody against caveolin-1 revealed that caveolin-1 was
      concentrated at the rear of moving cells. Similarly, monolayer scraping to induce
      random cell walk resulted in relocation of caveolin-1 to the cell rear. These
      results suggest that posterior polarization of caveolin-1 is a common feature
      both for chemotaxis and chemokinesis. Dual immunofluorescent labeling showed
      that, during cell spreading, caveolin-1 was compacted in the cell center and
      excluded from nascent focal contacts along the circular lamellipodium, as
      revealed by integrin beta1 and FAK staining. When cells were migrating, integrin
      beta1 and FAK appeared at polarized lamellipodia, whereas caveolin-1 was found at
      the posterior of moving cells. Notably, wherever caveolin-1 was polarized, there
      was a conspicuous absence of lamellipod protrusion. Transmission electron
      microscopy showed that caveolae, similar to their marker caveolin-1, were located
      at the cell center during cell spreading or at the cell rear during cell
      migration. In contrast to its unphosphorylated form, tyrosine-phosphorylated
      caveolin-1, upon fibronectin stimulation, was associated with the focal complex
      molecule phosphopaxillin along the lamellipodia of moving cells. Thus,
      unphosphorylated and phosphorylated caveolin-1 were located at opposite poles
      during cell migration. Importantly, loss of caveolin-1 polarity by targeted down
      regulation of the protein prevented cell polarization and directional movement.
      Our present results suggest a potential role of caveolin polarity in lamellipod
      extension and cell migration.

PMID- 15504730
TI  - Opposite effects of a single IIIS5 mutation on phenylalkylamine and
      dihydropyridine interaction with L-type Ca2+ channels.
AB  - Replacement of L-type Ca(2+) channel alpha(1) subunit residue Thr-1066 in segment
      IIIS5 by a tyrosine residue conserved in the corresponding positions of non-L
      type Ca(2+) channels eliminates high dihydropyridine sensitivity through a steric
      mechanism. To determine the effects of this mutation on phenylalkylamine
      interaction, we exploited the availability of Ca(v)1.2DHP(-/-) mice containing
      the T1066Y mutation. In contrast to dihydropyridines, increased protein-dependent
      binding of the phenylalkylamine (-)-[(3)H]devapamil occurred to Ca(v)1.2DHP(-/-)
      mouse brain microsomes. This effect could be attributed to an at least 2-fold
      increase in affinity as determined by saturation analysis and binding inhibition
      experiments. The latter also revealed a higher affinity for (-)-verapamil but not
      for (-)-gallopamil. The mutation caused a pronounced slowing of (-)
      [(3)H]devapamil dissociation, indicating a stabilization of the drug-channel
      complex. The increased affinity of mutant channels was also evident in functional
      studies after heterologous expression of wild type and T1066Y channels in Xenopus
      laevis oocytes. 100 mum (-)-verapamil inhibited a significantly larger fraction
      of Ba(2+) inward current through mutant than through WT channels. Our results
      provide evidence that phenylalkylamines also interact with the IIIS5 helix and
      that the geometry of the IIIS5 helix affects the access and/or binding of
      different chemical classes of Ca(2+) channel blockers to their overlapping
      binding domains. Mutation of Thr-1066 to a non-L-type tyrosine residue can be
      exploited to differentially affect phenylalkylamine and dihydropyridine binding
      to L-type Ca(2+) channels.

PMID- 15504731
TI  - Peptide YY and neuropeptide Y induce villin expression, reduce adhesion, and
      enhance migration in small intestinal cells through the regulation of CD63,
      matrix metalloproteinase-3, and Cdc42 activity.
AB  - Peptide YY (PYY) and neuropeptide Y (NPY) are regulatory peptides synthesized in
      the intestine and brain, respectively, that modify physiological functions
      affecting nutrient assimilation and feeding behavior. Because PYY and NPY also
      alter the expression of intestine-specific differentiation marker proteins and
      the tetraspanin CD63, which is involved in cell adhesion, we investigated whether
      intestinal cell differentiation could be linked to mucosal cell adhesion and
      migration through these peptides. PYY and NPY significantly decreased cell
      adhesion and increased cell migration in a dose-dependent manner prior to cell
      confluency in our model system, non-tumorigenic small intestinal hBRIE 380i
      cells. Both peptides reduced CD63 expression and CD63-dependent cell adhesion.
      CD63 overexpression increased and antisense CD63 cDNA decreased intestinal cell
      adhesion. In parallel, both PYY and NPY increased expression of matrix
      metalloproteinase-3 (MMP-3) to a level sufficient to induce cell migration by
      activating the Rho GTPase Cdc42. The effects of both peptides on cell migration
      were blocked in cells constitutively overexpressing dominant-negative Cdc42. PYY
      and NPY also significantly induced the expression of the differentiation marker
      villin, which could be eliminated by an MMP inhibitor at a concentration that
      inhibits cell migration. Increased MMP-3 activity, which enhanced cell migration,
      also induced villin mRNA levels. Therefore, these data indicate that the
      alteration of adhesion and migration by PYY and NPY occurs in part by synchronous
      modulation of three proteins that are involved in extracellular matrix
      basolateral membrane interactions, CD63, MMP-3 and Cdc42, and that PYY/NPY
      regulation of expression of mucosal proteins such as villin is linked to the
      process of cell migration and adhesion.

PMID- 15504732
TI  - A WRKY gene from creosote bush encodes an activator of the abscisic acid
      signaling pathway.
AB  - The creosote bush (Larrea tridentata) is a xerophytic evergreen C3 shrub thriving
      in vast arid areas of North America. As the first step toward understanding the
      molecular mechanisms controlling the drought tolerance of this desert plant, we
      have isolated a dozen genes encoding transcription factors, including LtWRKY21
      that encodes a protein of 314 amino acid residues. Transient expression studies
      with the GFP-LtWRKY21 fusion construct indicate that the LtWRKY21 protein is
      localized in the nucleus and is able to activate the promoter of an abscisic acid
      (ABA)-inducible gene, HVA22, in a dosage-dependent manner. The transactivating
      activity of LtWRKY21 relies on the C-terminal sequence containing the WRKY domain
      and a N-terminal motif that is essential for the repression activity of some
      regulators in ethylene signaling. LtWRKY21 interacts synergistically with ABA and
      transcriptional activators VP1 and ABI5 to control the expression of the HVA22
      promoter. Co-expression of VP1, ABI5, and LtWRKY21 leads to a much higher
      expression of the HVA22 promoter than does the ABA treatment alone. In contrast,
      the Lt-WRKY21-mediated transactivation is inhibited by two known negative
      regulators of ABA signaling: 1-butanol, an inhibitor of phospholipase D, and abi1
      1, a dominant negative mutant protein phosphatase. Interestingly, abi1-1 does not
      block the synergistic effect of LtWRKY21, VP1, and ABI5 co-expression, indicating
      that LtWRKY21, VP1, and ABI5 may form a complex that functions downstream of ABI1
      to control ABA-regulated expression of genes.

PMID- 15504733
TI  - Methionine adenosyltransferase:adrenergic-cAMP mechanism regulates a daily rhythm
      in pineal expression.
AB  - (S)-adenosylmethionine (SAM) is a critical element of melatonin synthesis as the
      methyl donor in the last step of the pathway, the O-methylation of N-acetyl 5
      hydroxytryptamine by hydroxyindole-O-methyltransferase. The activity of the
      enzyme that synthesizes SAM, methionine adenosyltransferase (MAT), increases 2.5
      fold at night in the pineal gland. In this study, we found that pineal MAT2A mRNA
      and the protein it encodes, MAT II, also increase at night, suggesting that the
      increase in MAT activity is caused by an increase in MAT II gene products. The
      night levels of MAT2A mRNA in the pineal gland were severalfold higher than in
      other neural and non-neural tissues examined, consistent with the requirement for
      SAM in melatonin synthesis. Related studies indicate that the nocturnal increase
      in MAT2A mRNA is caused by activation of a well described neural pathway that
      mediates photoneural-circadian regulation of the pineal gland. MAT2A mRNA and MAT
      II protein were increased in organ culture by treatment with norepinephrine (NE),
      the sympathetic neurotransmitter that stimulates the pineal gland at night. NE is
      known to markedly elevate pineal cAMP, and here it was found that cAMP agonists
      elevate MAT2A mRNA levels by increasing MAT2A mRNA synthesis and that drugs that
      block cAMP activation of cAMP dependent protein kinase block effects of NE.
      Therefore, the NE-cAMP dependent increase in pineal MAT activity seems to reflect
      an increase in MAT II protein, which occurs in response to cAMP-->protein kinase
      dependent increased MAT2A expression. The existence of this MAT regulatory system
      underscores the importance that MAT plays in melatonin biogenesis. These studies
      also point to the possibility that SAM production in other tissues might be
      regulated through cAMP.

PMID- 15504735
TI  - Dkk-1-derived synthetic peptides and lithium chloride for the control and
      recovery of adult stem cells from bone marrow.
AB  - It is established that human mesenchymal stem cells (hMSCs) from bone marrow are
      a source of osteoblast progenitors in vivo and under appropriate conditions,
      differentiate into osteoblasts ex vivo. Because hMSCs are recovered by iliac
      crest aspirate and enriched by virtue of their adherence to tissue culture
      plastic, the cells provide a convenient ex vivo model for the study of osteogenic
      tissue repair in an experimentally accessible system. Recent advances in the
      field of skeletal development and osteogenesis have demonstrated that signaling
      through the canonical wingless (Wnt) pathway is critical for the differentiation
      of progenitor cell lines into osteoblasts. Inhibition of such signals can
      predispose MSCs to cell cycle entry and inhibit osteogenesis. Here, we report
      that synthetic peptides derived from the second cysteine-rich domain of the
      canonical Wnt inhibitor Dickkopf-1 (Dkk-1) have utility in controlling the growth
      and recovery of hMSCs from bone marrow stroma. Three peptides corresponding to
      residues 217-269 in Dkk-1 were each found to enhance the proliferation of hMSCs
      in culture over 2 days. The most active peptide exhibited agonistic
      characteristics in that it ablated the proliferation lag observed when cultures
      of hMSCs receive fresh medium. It also reduced the expression of endogenous Dkk-1
      (Gregory, C. A., Singh, H., and Prockop, D. J. (2003) J. Biol. Chem. 278, 28067
      28078). When the cytosolic level of beta-catenin was elevated by addition of LiCl
      to cultures of hMSCs, the peptide also accelerated degradation of beta-catenin on
      withdrawal of lithium. A second peptide, corresponding to residues 184-204 had
      preferential and high affinity for hMSCs in the log phase of proliferation.
      Peptide overlay assays on hMSC lysates confirmed that the peptide bound to a 184
      kDa protein corresponding to the molecular mass of LRP6. Cells recovered by this
      peptide had enhanced osteogenic potential but less chondrogenic potential
      compared with controls. Because Wnt antagonists increase the number of non
      committed hMSCs in culture, they may be of use in increasing the rate of osseous
      wound healing in vivo by increasing the level of systemically migrating hMSCs.
      Therefore, such molecules could contribute to the development of a novel family
      of pharmaceutical agents for the improvement of the healing process in humans.

PMID- 15504734
TI  - ClC-3 chloride channels facilitate endosomal acidification and chloride
      accumulation.
AB  - We investigated the involvement of ClC-3 chloride channels in endosomal
      acidification by measurement of endosomal pH and chloride concentration [Cl-] in
      control versus ClC-3-deficient hepatocytes and in control versus ClC-3
      transfected Chinese hamster ovary cells. Endosomes were labeled with pH or [Cl-]
      sensing fluorescent transferrin (Tf), which targets to early/recycling endosomes,
      or alpha2-macroglobulin (alpha2M), which targets to late endosomes. In pulse
      label-chase experiments, [Cl-] was 19 mM just after internalization in alpha2M
      labeled endosomes in primary cultures of hepatocytes from wild-type mice,
      increasing to 58 mM over 45 min, whereas pH decreased from 7.1 to 5.4. Endosomal
      acidification and [Cl-] accumulation were significantly impaired in hepatocytes
      from ClC-3 knock-out mice, with [Cl-] increasing from 16 to 43 mM and pH
      decreasing from 7.1 to 6.0. Acidification and Cl- accumulation were blocked by
      bafilomycin. In Tf-labeled endosomes, [Cl-] was 46 mM in wild-type versus 35 mM
      in ClC-3-deficient hepatocytes at 15 min after internalization, with
      corresponding pH of 6.1 versus 6.5. Approximately 4-fold increased Cl-
      conductance was found in alpha2M-labeled endosomes isolated from hepatocytes of
      wild-type versus ClC-3 null mice. In contrast, Golgi acidification was not
      impaired in ClC-3-deficient hepatocytes. In transfected Chinese hamster ovary
      cells expressing ClC-3A, endosomal acidification and [Cl-] accumulation were
      enhanced. [Cl-] in alpha2M-labeled endosomes was 42 mM (control) versus 53 mM
      (ClC-3A) at 45 min, with corresponding pH 5.8 versus 5.2; [Cl-] in Tf-labeled
      endosomes at 15 min was 37 mM (control) versus 49 mM (ClC-3A) with pH 6.3 versus
      5.9. Our results provide direct evidence for involvement of ClC-3 in endosomal
      acidification by Cl- shunting of the interior-positive membrane potential created
      by the vacuolar H+ pump.

PMID- 15504736
TI  - RNA interference analyses suggest a transcript-specific regulatory role for
      mitochondrial RNA-binding proteins MRP1 and MRP2 in RNA editing and other RNA
      processing in Trypanosoma brucei.
AB  - Mitochondrial RNA-binding proteins MRP1 and MRP2 occur in a heteromeric complex
      that appears to play a role in U-insertion/deletion editing in trypanosomes.
      Reduction in the levels of MRP1 (gBP21) and/or MRP2 (gBP25) mRNA by RNA
      interference in procyclic Trypanosoma brucei resulted in severe growth
      inhibition. It also resulted in the loss of both proteins, even when only one of
      the MRP mRNAs was reduced, indicating a mutual dependence for stability.
      Elimination of the MRPs gave rise to substantially reduced levels of edited CyB
      and RPS12 mRNAs but little or no reduction of the level of edited Cox2, Cox3, and
      A6 mRNAs as measured by poisoned primer extension analyses. In contrast, edited
      NADH-dehydrogenase (ND) subunit 7 mRNA was increased 5-fold in MRP1+2 double
      knock-down cells. Furthermore, MRP elimination resulted in reduced levels of
      Cox1, ND4, and ND5 mRNAs, which are never edited, whereas mitoribosomal 12 S rRNA
      levels were not affected. These data indicate that MRP1 and MRP2 are not
      essential for RNA editing per se but, rather, play a regulatory role in the
      editing of specific transcripts and other RNA processing activities.

PMID- 15504737
TI  - JNK2 translocates to the mitochondria and mediates cytochrome c release in PC12
      cells in response to 6-hydroxydopamine.
AB  - 6-Hydroxydopamine (6-OHDA) causes death of dopaminergic neurons by mitochondrial
      dysfunction with JNKs as central mediators. Here we provide novel insights into
      specific actions of JNK isoforms in 6-OHDA-induced death of PC12 cells. Twenty
      five mum 6-OHDA enhanced total JNK activity in the cytoplasm, nucleus, and at the
      mitochondria. Inhibition of JNKs by 2 mum SP600125 or transfection with dominant
      negative JNK2 (dnJNK2) rescued more than 60% of the otherwise dying PC12 cells
      after 24 h, whereas transfection with dnJNK1 had no protective effects. In
      contrast to constitutively present JNK1, JNK2 amounts increased in the nucleus
      and at the mitochondria after 6-OHDA stimulation. JNK inhibition by SP600125 or
      transfection of dnJNK2 reduced the pool of active JNKs in the nucleus, the
      release of cytochrome c, as well as the cleavage of caspase-3 and its substrate
      poly(ADP-ribose) polymerase-1. Transfection with dnJNK1, however, had no effects
      on the translocation of JNKs to the mitochondria or the release of cytochrome c.
      Our data provide novel functional insights into the pathological role of
      individual JNK isoforms, the signalosome at the mitochondria, and the mode of JNK
      induced release of cytochrome c.

PMID- 15504738
TI  - Genes affecting the cell cycle, growth, maintenance, and drug sensitivity are
      preferentially regulated by anti-HER2 antibody through phosphatidylinositol 3
      kinase-AKT signaling.
AB  - The molecular mechanisms by which the anti-HER2 antibodies trastuzumab and its
      murine equivalent 4D5 inhibit tumor growth and potentiate chemotherapy are not
      fully understood. Inhibition of signaling through the phosphatidylinositol 3
      kinase (PI3K)-AKT pathway may be particularly important. Treatment of breast
      cancer cells that overexpress HER2 with trastuzumab inhibited HER2-HER3
      association, decreased PDK1 activity, reduced Thr-308 and Ser-473 phosphorylation
      of AKT, and reduced AKT enzymatic activity. To place the role of PI3K-AKT in
      perspective, gene expression was studied by using Affymetrix microarrays and real
      time reverse transcription-PCR. Sixteen genes were consistently down-regulated
      2.0-4.9-fold in two antibody-treated breast cancer cell lines. Fourteen of the 16
      genes were involved in three major functional areas as follows: 7 in cell cycle
      regulation, particularly of the G(2)-M; 5 in DNA repair/replication; and 2 in
      modifying chromatin structure. Of the 16 antibody-regulated genes, 64% had roles
      in cell growth/maintenance and 52% contributed to the cell cycle. Direct
      inhibition of PI3K with an inhibitor markedly reduced expression of 14 genes that
      were also affected by the antibody. Constitutive activation of AKT1 blocked the
      effect of the anti-HER2 antibody on cell cycle arrest and on eight differentially
      expressed genes. The antibody enhanced docetaxel-induced growth inhibition but
      did not increase the fraction of apoptotic cells induced with docetaxel alone. In
      contrast, the antibody plus docetaxel markedly down-regulated two genes, HEC and
      DEEPEST, required for passage through G(2)-M. Thus, anti-HER2 antibody
      preferentially affects genes contributing to cell cycle progression and cell
      growth/maintenance, in part through the PI3K-AKT signaling. Transcriptional
      regulation by anti-HER2 antibody through PI3K-AKT pathway may potentiate the
      growth inhibitory activity of docetaxel by affecting cell cycle progression.

PMID- 15504739
TI  - MicroRNA-143 regulates adipocyte differentiation.
AB  - MicroRNAs (miRNAs) are endogenously expressed 20-24 nucleotide RNAs thought to
      repress protein translation through binding to a target mRNA (1-3). Only a few of
      the more than 250 predicted human miRNAs have been assigned any biological
      function. In an effort to uncover miRNAs important during adipocyte
      differentiation, antisense oligonucleotides (ASOs) targeting 86 human miRNAs were
      transfected into cultured human pre-adipocytes, and their ability to modulate
      adipocyte differentiation was evaluated. Expression of 254 miRNAs in
      differentiating adipocytes was also examined on a miRNA microarray. Here we
      report that the combination of expression data and functional assay results
      identified a role for miR-143 in adipocyte differentiation. miR-143 levels
      increased in differentiating adipocytes, and inhibition of miR-143 effectively
      inhibited adipocyte differentiation. In addition, protein levels of the proposed
      miR-143 target ERK5 (4) were higher in ASO-treated adipocytes. These results
      demonstrate that miR-143 is involved in adipocyte differentiation and may act
      through target gene ERK5.

PMID- 15504740
TI  - Analysis of the membrane topology of the acid-sensing ion channel 2a.
AB  - Acid-sensing ion channels, or ASICs, are members of the amiloride-sensitive
      cationic channel superfamily that are predicted to have intracellular amino and
      carboxyl termini and two transmembrane domains connected by a large extracellular
      loop. This prediction comes from biochemical studies of the mammalian epithelial
      sodium channels where glycosylation mutants identified the extracellular regions
      of the channel and a combination of antibody sensitivity and protease action
      substantiated the intracellular nature of the amino and carboxyl termini.
      However, although there are highly conserved regions within the different cation
      channel family members, membrane topology prediction programs provide several
      alternative structures for the ASICs. Thus, we used glycosylation studies to
      define the actual membrane topology of the ASIC2a subtype. We deleted the five
      predicted endogenous asparagine-linked glycosylation sites (Asn-Xaa-(Ser/Thr)) at
      Asn-22, Asn-365, Asn-392, Asn-478, and Asn-487 to map the extracellular topology.
      We then introduced exogenous asparagine-linked glycosylation sites at Lys-4, Pro
      37, Arg-63, Tyr-67, His-72, Ala-81, Tyr-414, Tyr-423, and Tyr-453 to define the
      transmembrane domain borders. Finally, we used cell permeabilization studies to
      confirm the intracellular amino termini of ASIC2a. The data show that Asn-365 and
      Asn-392 are extracellular and that the introduction of asparagine-linked
      glycosylation sites at His-72, Ala-81, Tyr-414, and Tyr-423 leads to an increase
      in molecular mass consistent with an extracellular apposition. In addition,
      heterologous expression of ASIC2a requires membrane permeabilization for antibody
      staining. These data confirm the membrane topology prediction that the ASIC2a
      subtype consists of intracellular amino and carboxyl termini and two
      transmembrane domains connected by a large extracellular loop.

PMID- 15504741
TI  - On the mechanism for neomycin reversal of wortmannin inhibition of insulin
      stimulation of glucose uptake.
AB  - Although a number of studies and approaches have indicated that activation of the
      Ser/Thr kinase called Akt/protein kinase B is critical for the insulin-stimulated
      increase of glucose uptake in adipocytes, other studies have indicated that this
      enzyme may play an ancillary role. For example, a recent study indicated that
      neomycin would allow insulin-stimulated Glut4 translocation and glucose transport
      in the presence of the phosphatidylinositol (PI) 3-kinase inhibitor, wortmannin,
      a known inhibitor of Akt activation (James, D. J., Salaun, C., Brandie, F. M.,
      Connell, J. M. C., and Chamberlain, L. H. (2004) J. Biol. Chem. 279, 20567
      20570). To better understand this observation, we examined a number of downstream
      targets of Akt. As previously reported, treatment of 3T3-L1 adipocytes with
      neomycin prevented the wortmannin inhibition of insulin-stimulated glucose
      transport. However, in the presence of neomycin, wortmannin did not inhibit the
      insulin-stimulated phosphorylation of several downstream targets of Akt including
      a proline-rich Akt substrate of 40 kDa, ribosomal protein S6, and glycogen
      synthase kinase-3. In addition, neomycin did not prevent the ability of a
      structurally unrelated PI 3-kinase inhibitor, LY294002, to inhibit the insulin
      stimulated activation of glucose uptake. Moreover, neomycin reversed the
      inhibitory effect of wortmannin but not LY294002 on insulin stimulation of Akt
      kinase activity. Finally, neomycin was found to inactivate in vitro the PI 3
      kinase inhibitory actions of wortmannin but not LY294002. These results indicate
      that the effects of neomycin in adipocytes are not mediated via its ability to
      sequester phosphatidylinositol 4,5-bisphosphate but are instead caused by the
      ability of neomycin to inactivate wortmannin.

PMID- 15504742
TI  - Human placenta secretes apolipoprotein B-100-containing lipoproteins.
AB  - Supply of lipids from the mother is essential for fetal growth and development.
      In mice, disruption of yolk sac cell secretion of apolipoprotein (apo) B
      containing lipoproteins results in embryonic lethality. In humans, the yolk sac
      is vestigial. Nutritional functions are instead established very early during
      pregnancy in the placenta. To examine whether the human placenta produces
      lipoproteins, we examined apoB and microsomal triglyceride transfer protein (MTP)
      mRNA expression in placental biopsies. ApoB and MTP are mandatory for assembly
      and secretion of apoB-containing lipoproteins. Both genes were expressed in
      placenta and microsomal extracts from human placenta contained triglyceride
      transfer activity, indicating expression of bioactive MTP. To detect lipoprotein
      secretion, biopsies from term placentas were placed in medium with
      [(35)S]methionine and [(35)S]cysteine for 3-24 h. Upon sucrose gradient
      ultracentrifugation of the labeled medium, fractions were analyzed by apoB
      immunoprecipitation. (35)S-labeled apoB-100 was recovered in d approximately 1.02
      1.04 g/ml particles (i.e. similar to the density of plasma low density
      lipoproteins). Electron microscopy of negatively stained lipoproteins secreted
      from placental tissue showed spherical particles with a diameter of 47 +/- 10 nm.
      These results demonstrate that human placenta expresses both apoB and MTP and
      consequently synthesize and secrete apoB-100-containing lipoproteins. Placental
      lipoprotein formation constitutes a novel pathway of lipid transfer from the
      mother to the developing fetus.

PMID- 15504743
TI  - Involvement of the c-Src-Crk-C3G-Rap1 signaling in the nectin-induced activation
      of Cdc42 and formation of adherens junctions.
AB  - Nectins, Ca(2+)-independent immunoglobulin-like cell-cell adhesion molecules,
      induce the activation of Cdc42 and Rac small G proteins, enhancing the formation
      of cadherin-based adherens junctions (AJs) and claudin-based tight junctions.
      Nectins recruit and activate c-Src at the nectin-based cell-cell contact sites. c
      Src then activates Cdc42 through FRG, a Cdc42-GDP/GTP exchange factor. We showed
      here that Rap1 small G protein was involved in the nectin-induced activation of
      Cdc42 and formation of AJs. Rap1 was recruited to the nectin-based cell-cell
      contact sites and locally activated through the c-Src-Crk-C3G signaling there.
      The activation of either c-Src or Rap1 alone was insufficient for and the
      activation of both molecules was essential for the activation of FRG. The
      activation of Rap1 was not necessary for the c-Src-mediated phosphorylation or
      recruitment of FRG. The inhibition of the Crk, C3G, or Rap1 signaling reduced the
      formation of AJs. These results indicate that Rap1 is activated by nectins
      through the c-Src-Crk-C3G signaling and involved in the nectin-induced, c-Src-
      and FRG-mediated activation of Cdc42 and formation of AJs.

PMID- 15504744
TI  - Phosphorylation of NG2 proteoglycan by protein kinase C-alpha regulates polarized
      membrane distribution and cell motility.
AB  - Protein kinase C (PKC)-alpha phosphorylation of recombinant NG2 cytoplasmic
      domain and phorbol ester-induced PKC-dependent phosphorylation of full-length NG2
      expressed in U251 cells are both blocked by mutation of Thr(2256), identifying
      this residue as a primary phosphorylation site. In untreated U251/NG2 cells, NG2
      is present along with ezrin and alpha(3)beta(1) integrin in apical cell surface
      protrusions. Phorbol ester treatment causes redistribution of all three
      components to lamellipodia, accompanied by increased cell motility. U251 cells
      expressing NG2 with a valine substitution at position 2256 are resistant to
      phorbol ester treatment: NG2 remains in membrane protrusions and cell motility is
      unchanged. In contrast, NG2 with a glutamic acid substitution at position 2256
      redistributes to lamellipodia even without phorbol ester treatment, rendering
      transfected U251 cells spontaneously motile. PKC-alpha-mediated NG2
      phosphorylation at Thr(2256) is therefore a key step for initiating cell
      polarization and motility.

PMID- 15504745
TI  - Rac GTPase isoform-specific regulation of NADPH oxidase and chemotaxis in murine
      neutrophils in vivo. Role of the C-terminal polybasic domain.
AB  - The Rho family GTPase Rac acts as a molecular switch for signal transduction to
      regulate various cellular functions. Mice deficient in the hematopoietic-specific
      Rac2 isoform exhibit agonist-specific defects in neutrophil chemotaxis and
      superoxide production, despite expression of the highly homologous Rac1 isoform.
      To examine whether functional defects in rac2(-/-) neutrophils reflect effects of
      an overall decrease in total cellular Rac or an isoform-specific role for Rac2,
      retroviral vectors were used to express exogenous Rac1 or Rac2 at levels similar
      to endogenous. In rac2(-/-) neutrophils differentiated from transduced myeloid
      progenitors in vitro, increasing cellular Rac levels by expression of either
      exogenous Rac1 or Rac2 increased formylmethionylleucylphenylalanine- or phorbol
      ester-stimulated NADPH oxidase activity. Of note, placement of an epitope tag on
      the N terminus of Rac1 or Rac2 blunted reconstitution of responses in rac2(-/-)
      neutrophils. In rac2(-/-) neutrophils isolated from mice transplanted with Rac
      transduced bone marrow cells, superoxide production and chemotaxis were fully
      reconstituted by expression of exogenous Rac2, but not Rac1. A chimeric Rac1
      protein in which the Rac1 C-terminal polybasic domain, which contains six lysines
      or arginines, was replaced with that of the human Rac2 polybasic domain
      containing only three basic residues, also reconstituted superoxide production
      and chemotaxis, whereas expression of a Rac2 derivative in which the polybasic
      domain was replaced with that of Rac1 did not and resulted in disoriented cell
      motility. Thus, the composition of the polybasic domain is sufficient for
      determining Rac isoform specificity in the production of superoxide and
      chemotaxis in murine neutrophils in vivo.

PMID- 15504746
TI  - Mu-opioid receptor desensitization: is morphine different?
AB  - Opioid tolerance and dependence are important phenomena. The contribution of
      acute mu-opioid receptor regulatory mechanisms to the development of analgesic
      tolerance or physical dependence are unknown, and even the mechanisms underlying
      relatively rapid receptor desensitization in single cells are unresolved. To a
      large degree, the uncertainty surrounding the mechanisms and consequences of
      short-term regulation of tau-opioid receptors in single cells arises from the
      limitations in the experimental design in many of the studies that have
      investigated these events. Receptor overexpression and use of assays in which
      regulatory mechanisms are likely to blunt control determinations have led to
      measurements of opioid receptor activity that are likely to be insensitive to
      receptor uncoupling. Together with uncertainties concerning molecular details of
      tau-opioid receptor interactions with potential regulatory molecules such as G
      protein-coupled receptor kinases and arrestins, we are left with an incomplete
      picture crudely copied from the well-worked-out regulatory schema for beta(2)
      adrenoceptors. As a consequence, suggestions that clinically relevant tau-opioid
      receptor agonists may have different propensities to produce tolerance and
      dependence that arise from their differential recruitment of regulatory
      mechanisms are premature, and have not yet been appropriately assessed, nor
      explained in the context of a thoroughly established regulatory scheme. In this
      commentary, we outline the experimental limitations that have given rise to
      conflicting ideas about how mu-opioid receptors are regulated, and identify the
      issues we feel still need to be addressed before we can understand why morphine
      promotes receptor trafficking differently to other opioids.

PMID- 15504748
TI  - Protein kinase C activation inhibits eosinophil degranulation through stimulation
      of intracellular cAMP production.
AB  - The mechanism of inhibition of eosinophil degranulation by protein kinase C (PKC)
      was investigated in complement C5a (C5a)-stimulated degranulation of highly
      purified human eosinophils using the specific PKC activator - phorbol 12
      myristate 13-acetate (PMA). C5a-induced release of eosinophil peroxidase and
      eosinophil cationic protein was potently inhibited in a concentration-dependent
      manner by PMA (IC(50): 3 and 5 nM, respectively). The inhibition by PMA, but not
      histamine, was significantly reversed by the specific, but isoform nonselective,
      PKC inhibitor Ro 31-8220 (1 microM). In the presence of phosphodiesterase
      inhibitor rolipram (5 microM), PMA stimulated a pronounced concentration
      dependent increase in intracellular cAMP, with a potency 400 times that of
      histamine (EC(50): 55 nM vs 22.5 microM). The inactive PMA analogue, 4alpha-PMA,
      had no such effect. The cAMP production by PMA, but not histamine, was
      significantly reversed by Ro 31-8220 (1 microM) and the selective inhibitor of
      the novel PKCdelta, rottlerin (1-3 microM), but not the selective inhibitor of
      the classical PKC isoforms, Go 6976 (0.01-0.1 microM). Western blot analysis
      revealed the presence of six PKC isoforms (alpha, betaI, betaII, delta, iota and
      zeta) in isolated eosinophils. Chelation of internal or external calcium had no
      effect on PMA-induced cAMP response, but abolished that induced by histamine.
      There was a good correlation between increase in intracellular cAMP and
      inhibition of degranulation. These results show, for the first time, that in
      human eosinophils, PMA, via activation of PKCdelta isoform, can stimulate cAMP
      production, and that this may be the basis for its potent anti-degranulatory
      effect.

PMID- 15504747
TI  - Cardiovascular effects of sphingosine-1-phosphate and other sphingomyelin
      metabolites.
AB  - Upon various stimuli, cells metabolize sphingomyelin from the cellular plasma
      membrane to form sphingosylphosphorylcholine (SPC) or ceramide. The latter can be
      further metabolized to sphingosine and then sphingosine-1-phosphate (S1P). Apart
      from local formation, S1P and SPC are major constituents of blood plasma. All
      four sphingomyelin metabolites (SMM) can act upon intracellular targets, and at
      least S1P and probably also SPC can additionally act upon G-protein-coupled
      receptors. While the molecular identity of the SPC receptors remains unclear,
      several subtypes of S1P receptors have been cloned and their distribution in
      cardiovascular tissues is described. In the heart SMM can alter intracellular
      Ca(2+) release, particularly via the ryanodine receptor, and conductance of
      various ion channels in the plasma membrane, particularly I(K(Ach)). While the
      various SMM differ somewhat in their effects, the above alterations of ion
      homeostasis result in reduced cardiac function in most cases, and ceramide and/or
      sphingosine may be the mediators of the negative inotropic effects of tumour
      necrosis factor. In the vasculature, SMM mainly act as acute vasoconstrictors in
      most vessels, but ceramide can be a vasodilator. SMM-induced vasoconstriction
      involves mobilization of Ca(2+) from intracellular stores, influx of
      extracellular Ca(2+) via L-type channels and activation of a rho-kinase. Extended
      exposure to SMM, particularly S1P, promotes several stages of the angiogenic
      process like endothelial cell activation, migration, proliferation, tube
      formation and vascular maturation. We propose that SMM are an important class of
      endogenous modulators of cardiovascular function.

PMID- 15504749
TI  - Selective inhibition of sodium-calcium exchanger by SEA-0400 decreases early and
      delayed after depolarization in canine heart.
AB  - The sodium-calcium exchanger (NCX) was considered to play an important role in
      arrhythmogenesis under certain conditions such as heart failure or calcium
      overload. In the present study, the effect of SEA-0400, a selective inhibitor of
      the NCX, was investigated on early and delayed afterdepolarizations in canine
      ventricular papillary muscles and Purkinje fibres by applying conventional
      microelectrode techniques at 37 degrees C. The amplitude of both early and
      delayed afterdepolarizations was markedly decreased by 1 microM SEA-0400 from
      26.6+/-2.5 to 14.8+/-1.8 mV (n=9, P<0.05) and from 12.5+/-1.7 to 5.9+/-1.4 mV
      (n=3, P<0.05), respectively. In enzymatically isolated canine ventricular
      myocytes, SEA-0400 did not change significantly the L-type calcium current and
      the intracellular calcium transient, studied using the whole-cell configuration
      of the patch-clamp technique and Fura-2 ratiometric fluorometry. It is concluded
      that, through the reduction of calcium overload, specific inhibition of the NCX
      current by SEA-0400 may abolish triggered arrhythmias.

PMID- 15504750
TI  - The HIV protease inhibitor ritonavir synergizes with butyrate for induction of
      apoptotic cell death and mediates expression of heme oxygenase-1 in DLD-1 colon
      carcinoma cells.
AB  - The protease inhibitor ritonavir is an integral part of current antiretroviral
      therapy targeting human immunodeficiency virus. Recent studies demonstrate that
      ritonavir induces apoptotic cell death with high efficiency in lymphoblastoid
      cell lines. Moreover, ritonavir can suppress activation of the transcription
      factor nuclear factor-kappaB and is an inhibitor of interleukin-1beta and tumor
      necrosis factor-alpha production in peripheral blood mononuclear cells. Thus,
      ritonavir appears to have anti-inflammatory properties. In the present study, we
      investigated in DLD-1 colon carcinoma cell effects of ritonavir on apoptotic cell
      death and expression of heme oxygenase-1 (HO-1), an anti-inflammatory enzyme that
      may be critically involved in the modulation of colonic inflammation. Compared to
      unstimulated control, ritonavir resulted in a moderate increase in the rate of
      apoptotic cell death as observed after 20 h of incubation. Notably, ritonavir
      potently synergized with the short-chain fatty acid butyrate for induction of
      caspase-3-dependent apoptosis in DLD-1 cells. Ritonavir enhanced mRNA and protein
      expression of HO-1 in DLD-1 cells. Ritonavir-induced HO-1 protein was suppressed
      by SB203580 or SB202190 and preceded by immediate upregulation of cellular c-Fos
      and c-Jun protein levels. This process was associated with induction of activator
      protein-1 as detected by electrophoretic mobility shift analysis. The present
      data suggest that ritonavir has the potential to curb colon carcinogenesis by
      reducing cell growth via mechanisms that include apoptosis and by simultaneously
      modulating colonic inflammation via induction of anti-inflammatory HO-1.

PMID- 15504751
TI  - KATP-channel-induced vasodilation is modulated by the Na,K-pump activity in
      rabbit coronary small arteries.
AB  - The purpose of the study was to evaluate the importance of the Na,K-pump in
      relaxations induced by K(ATP)-channel openers in rabbit coronary small arteries.
      Arterial segments were mounted in myographs for recording of isometric tension.
      Whole-cell patch clamp was used to assess K(ATP)-channel currents in isolated
      smooth muscle cells from the arteries. In arteries preconstricted with the
      thromboxane A(2) analogue U46619 pinacidil and cromakalim induced concentration
      dependent relaxations. In arteries preconstricted with potassium (124 mM) only
      high concentrations of pinacidil had a small relaxant effect. In arteries
      preconstricted with U46619 pinacidil-induced relaxations were unaffected by
      pretreatment with N(omega)-nitro-L-arginine (L-NNA) and only slightly reduced
      after mechanical removal of the endothelium. Pinacidil induced relaxations were
      not significantly affected by 1 microM glibenclamide. However, the relaxations
      were partly inhibited in potassium-free media and by 1 microM ouabain. In
      contrast, the concentration-dependent relaxation to cromakalim was partly blocked
      by 1 microM glibenclamide and partly by 1 microM ouabain and when both drugs were
      present the inhibition increased. Ouabain (1 microM) and glibenclamide (1 microM)
      each partly inhibited an ATP-sensitive current induced by pinacidil and
      cromakalim. In the presence of both inhibitors a greater inhibition was seen.
      When the solution in the patch pipette was sodium-free the current was reduced
      and ouabain had no effect. The study suggests that the relaxation to cromakalim
      and most likely pinacidil is mediated through opening of K(ATP) channels.
      Inhibition of the Na,K-pump, however, may change the local environment for the
      K(ATP) channels (i.e. increases the ATP/ADPratio and/or decreases the
      transmembrane potassium gradient), which partly prevents the activation of the
      K(ATP)-channel current.

PMID- 15504752
TI  - Role of hydrogen sulphide in haemorrhagic shock in the rat: protective effect of
      inhibitors of hydrogen sulphide biosynthesis.
AB  - Haemorrhagic shock (60 min) in the anaesthetized rat resulted in a prolonged fall
      in the mean arterial blood pressure (MAP) and heart rate (HR). Pre-treatment (30
      min before shock) or post-treatment (60 min after shock) with inhibitors of
      cystathionine gamma lyase (CSE; converts cysteine into hydrogen sulphide
      (H(2)S)), dl-propargylglycine or beta-cyanoalanine (50 mg kg(-1), i.v.), or
      glibenclamide (40 mg kg(-1), i.p.), produced a rapid, partial restoration in MAP
      and HR. Neither saline nor DMSO affected MAP or HR. Plasma H(2)S concentration
      was elevated 60 min after blood withdrawal (37.5+/-1.3 microM, n=18 c.f. 28.9+/
      1.4 microM, n=15, P<0.05). The conversion of cysteine to H(2)S by liver (but not
      kidney) homogenates prepared from animals killed 60 min after withdrawal of blood
      was significantly increased (52.1+/-1.6 c.f. 39.8+/-4.1 nmol mg protein(-1), n=8,
      P<0.05), as was liver CSE mRNA (2.7 x). Both PAG (IC(50), 55.0+/-3.2 microM) and
      BCA (IC(50), 6.5+/-1.2 microM) inhibited liver H(2)S synthesizing activity in
      vitro. Pre-treatment of animals with PAG or BCA (50 mg kg(-1), i.p.) but not
      glibenclamide (40 mg kg(-1), i.p., K(ATP) channel inhibitor) abolished the rise
      in plasma H(2)S in animals exposed to 60 min haemorrhagic shock and prevented the
      augmented biosynthesis of H(2)S from cysteine in liver. These results demonstrate
      that H(2)S plays a role in haemorrhagic shock in the rat. CSE inhibitors may
      provide a novel approach to the treatment of haemorrhagic shock.

PMID- 15504753
TI  - Effects of grapefruit juice and orange juice components on P-glycoprotein- and
      MRP2-mediated drug efflux.
AB  - We investigated the effects of grapefruit juice (GFJ) and orange juice (OJ) on
      drug transport by MDR1 P-glycoprotein (P-gp) and multidrug resistance protein 2
      (MRP2), which are efflux transporters expressed in human small intestine. We
      examined the transcellular transport and uptake of [(3)H]vinblastine (VBL) and
      [(14)C]saquinavir in a human colon carcinoma cell line (Caco-2) and in porcine
      kidney epithelial cell lines transfected with human MDR1 cDNA and human MRP2
      cDNA, LLC-GA5-COL150, and LLC-MRP2, respectively. In Caco-2 cells, the basal-to
      apical transports of [(3)H]VBL and [(14)C]saquinavir were greater than those in
      the opposite direction. The ratio of basal-to-apical transport to apical-to-basal
      transport of [(3)H]VBL and [(14)C]saquinavir by Caco-2 cells was reduced in the
      presence of MK571 (MRPs inhibitor), verapamil (P-gp inhibitor), cyclosporin A
      (inhibitor of both), 50% ethyl acetate extracts of GFJ and OJ, or their
      components (6',7'-dihydroxybergamottin, bergamottin, tangeretin,
      hepatomethoxyflavone, and nobiletin). Studies of transport and uptake of
      [(3)H]VBL and [(14)C]saquinavir with MDR1 and MRP2 transfectants showed that VBL
      and saquinavir are transported by both P-gp and MRP2. GFJ and OJ components
      inhibited the transport by MRP2 as well as P-gp. However, their inhibitory
      potencies for P-gp or MRP2 were substrate-dependent. The present study has
      revealed that GFJ and OJ interact with not only P-gp but also MRP2, both of which
      are expressed at apical membranes and limit the apical-to-basal transport of VBL
      and saquinavir in Caco-2 cells.

PMID- 15504754
TI  - PPAR-gamma expression modulates insulin sensitivity in C2C12 skeletal muscle
      cells.
AB  - Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) expression is very
      low in skeletal muscle cells, which is one of the most important target tissues
      for insulin and plays a predominant role in glucose homeostasis. It has recently
      been shown that muscle-specific PPAR-gamma deletion in mouse causes insulin
      resistance. However, it is likely that the observed effects might be due to
      secondary interaction in whole animal. The aim of the study was to explore the
      role of muscle PPAR-gamma in insulin sensitivity. We stably transfected C2C12
      skeletal muscle cells with plasmids containing sense or antisense constructs of
      PPAR-gamma and examined the effect of modulation of PPAR-gamma expression in
      terms of glucose uptake. Effect was also examined in insulin-resistant C2C12
      skeletal muscle cells. In transfected C2C12 cell line, the inhibition of PPAR
      gamma expression (23.0 +/-0.005%) was observed to induce insulin resistance as
      determined by functional assessment of 2-deoxyglucose incorporation.
      Overexpression of PPAR-gamma (28.5 +/- 0.008%) produced an additional effect on
      insulin (100 nM) and Pioglitazone (50 microM), resulting in 42.7 +/- 3.5%
      increase in glucose uptake as against 29.2+/-2.8% in wild-type C2C12 skeletal
      muscle cells differentiated under normal (2% horse serum) condition. Under
      similar treatment, PPAR-gamma overexpressing cells resistant to insulin exhibited
      enhanced glucose uptake upto 60.7 +/- 4.08%, as compared to 23.8 +/- 5.1%
      observed in wild-type C2C12 skeletal muscle cells. These data demonstrate a
      direct involvement of PPAR-gamma in insulin sensitization of TZD action on
      skeletal muscle cells, and suggest that pharmacological overexpression of muscle
      PPAR-gamma gene in skeletal muscle might be a useful strategy for the treatment
      of insulin resistance.

PMID- 15504755
TI  - Plant alkaloid tetrandrine downregulates IkappaBalpha kinases-IkappaBalpha-NF
      kappaB signaling pathway in human peripheral blood T cell.
AB  - Plant alkaloid tetrandrine (Tet), purified from Chinese herb Han-Fang Chi, is a
      potent immunomodulator used to treat rheumatic disorders, silicosis and
      hypertension in mainland China. We previously demonstrated that Tet effectively
      suppresses cytokine production and proliferation of CD28-costimulated T cells. In
      the present study, we investigated the possible involvement of nuclear factor
      kappa B (NF-kappaB) transcription factors, critical in CD28 costimulation, in Tet
      mediated immunosuppression in human peripheral blood T cells. We showed that Tet
      inhibited NF-kappaB DNA-binding activities induced by various stimuli, including
      CD28 costimulation. At equal molar concentrations, Tet was as strong as
      methotrexate in suppressing CD28-costimulated NF-kappaB activities. Since Tet
      itself did not affect NF-kappaB binding to its corresponding DNA sequence, the
      results suggested that Tet might regulate NF-kappaB upstream signaling molecules.
      Further studies demonstrated that Tet could prevent the degradation of
      IkappaBalpha and inhibit nuclear translocation of p65 by blocking IkappaBalpha
      kinases alpha and beta activities. In addition, the activation of mitogen
      activated protein kinases such as c-jun N-terminal kinase, p38 and extracellular
      signal-regulated kinase and activator protein-1 DNA-binding activity were all
      downregulated by Tet. Transfection assays performed in purified human peripheral
      blood T cells also confirmed the inhibition of NF-kappaB transcriptional activity
      by Tet. When four Tet analogues were readily compared, dauricine appeared to
      preserve the most potent inhibition on CD28-costimulated but not on H(2)O(2)
      induced NF-kappaB DNA-binding activities. Our results provide the molecular basis
      of immunomodulation of Tet for being a potential disease-modifying antirheumatic
      drug in the therapy of autoimmune disorders like rheumatoid arthritis.

PMID- 15504756
TI  - Evidence for an apamin-sensitive, but not purinergic, component in the
      nonadrenergic noncholinergic relaxation of the rat gastric fundus.
AB  - The involvement of adenosine triphosphate (ATP) and carbon monoxide (CO) in the
      non-nitrergic nonpeptidergic component of high-frequency electrical field
      stimulation (EFS)-induced nonadrenergic noncholinergic (NANC) relaxation of
      longitudinal muscle strips from the rat gastric fundus was investigated. Under
      NANC conditions (1 microM atropine + 5 microM guanethidine), N(G)-nitro-L
      arginine methyl ester (L-NAME, 1 mM) slightly reduced the amplitude, but did not
      affect the area under the curve (AUC) of EFS (13 Hz, 2 min)-induced relaxation of
      9,11-dideoxy-9alpha,11alpha-methanoepoxy prostaglandin F(2alpha) (U46619, 0.1
      microM)-precontracted strips. With L-NAME (1 mM) plus alpha-chymotrypsin (1 U ml(
      1)), the amplitude and the AUC of relaxation were reduced to approximately two
      third and one-third of controls, respectively. Pyridoxal-phosphate-6-azophenyl
      2',4'-disulphonic acid (100 microM), apamin (0.3 microM), desensitization to ATP,
      suramin (100 microM), zinc protoporphyrin IX (300 microM) or ferrous haemoglobin
      (100 microM) did not inhibit the component of relaxation resistant to L-NAME plus
      alpha-chymotrypsin. L-NAME (1 mM) plus anti-vasoactive intestinal peptide (VIP)
      serum (1 : 100) reduced the amplitude and the AUC of relaxation to a similar
      extent as L-NAME (1 mM) plus alpha-chymotrypsin (1 U ml(-1)). Adding apamin (0.1
      microM) to L-NAME (1 mM) plus anti-VIP serum (1 : 100) further reduced the
      amplitude and the AUC of relaxation. These findings suggest that the non
      nitrergic nonpeptidergic component of NANC relaxation of the rat gastric fundus
      induced by high-frequency stimulation is mediated by a neurotransmitter that acts
      through apamin-sensitive mechanisms, that is neither ATP nor CO.

PMID- 15504757
TI  - VIP enhances both pre- and postsynaptic GABAergic transmission to hippocampal
      interneurones leading to increased excitatory synaptic transmission to CA1
      pyramidal cells.
AB  - Vasoactive intestinal peptide (VIP) is present in the hippocampus in three
      subtypes of GABAergic interneurones, two of which innervate preferentially other
      interneurones, responsible for pyramidal cell inhibition. We investigated how pre
      and postsynaptic modulation of GABAergic transmission (to both pyramidal cells
      and interneurones) by VIP could influence excitatory synaptic transmission in the
      CA1 area of the hippocampus. VIP (0.1-100 nM) increased [(3)H]GABA release from
      hippocampal synaptosomes (maximum effect at 1 nM VIP; 63.8 +/- 4.0%) but did not
      change [(3)H]glutamate release. VIP (0.3-30 nM) enhanced synaptic transmission in
      hippocampal slices (maximum effect at 1 nM VIP; field excitatory postsynaptic
      potentials (epsp) slope: 23.7 +/- 1.1%; population spike amplitude: 20.3 +/-
      1.7%). The action on field epsp slope was fully dependent on GABAergic
      transmission since it was absent in the presence of picrotoxin (50 microM) plus
      CGP55845 (1 microM). VIP (1 nM) did not change paired-pulse facilitation but
      increased paired-pulse inhibition in CA1 pyramidal cells (16.0 +/- 0.9%),
      reinforcing the involvement of GABAergic transmission in the action of VIP. VIP
      (1 nM) increased muscimol-evoked inhibitory currents by 36.4 +/- 8.7% in eight
      out of ten CA1 interneurones in the stratum radiatum. This suggests that VIP
      promotes increased inhibition of interneurones that control pyramidal cells,
      leading to disinhibition of synaptic transmission to pyramidal cell dendrites. In
      conclusion, concerted pre- and postsynaptic actions of VIP lead to disinhibition
      of pyramidal cell dendrites causing an enhancement of synaptic transmission.

PMID- 15504758
TI  - Electrophysiological characterization of the SK channel blockers methyl
      laudanosine and methyl-noscapine in cell lines and rat brain slices.
AB  - We have recently shown that the alkaloid methyl-laudanosine blocks SK channel
      mediated afterhyperpolarizations (AHPs) in midbrain dopaminergic neurones.
      However, the relative potency of the compound on the SK channel subtypes and its
      ability to block AHPs of other neurones were unknown. Using whole-cell patch
      clamp experiments in transfected cell lines, we found that the compound blocks
      SK1, SK2 and SK3 currents with equal potency: its mean IC(50)s were 1.2, 0.8 and
      1.8 microM, respectively. IK currents were unaffected. In rat brain slices,
      methyl-laudanosine blocked apamin-sensitive AHPs in serotonergic neurones of the
      dorsal raphe and noradrenergic neurones of the locus coeruleus with IC(50)s of 21
      and 19 microM, as compared to 15 microM in dopaminergic neurones. However, at 100
      microM, methyl-laudanosine elicited a constant hyperpolarization of serotonergic
      neurones of about 9 mV, which was inconsistently (i.e. not in a reproducible
      manner) antagonized by atropine and hence partly due to the activation of
      muscarinic receptors. While exploring the pharmacology of related compounds, we
      found that methyl-noscapine also blocked SK channels. In cell lines, methyl
      noscapine blocked SK1, SK2 and SK3 currents with mean IC(50)s of 5.9, 5.6 and 3.9
      microM, respectively. It also did not block IK currents. Methyl-noscapine was
      slightly less potent than methyl-laudanosine in blocking AHPs in brain slices,
      its IC(50)s being 42, 37 and 29 microM in dopaminergic, serotonergic and
      noradrenergic neurones, respectively. Interestingly, no significant non-SK
      effects were observed with methyl-noscapine in slices. At a concentration of 300
      microM, methyl-noscapine elicited the same changes in excitability in the three
      neuronal types than did a supramaximal concentration of apamin (300 nM). Methyl
      laudanosine and methyl-noscapine produced a rapidly reversible blockade of SK
      channels as compared with apamin. The difference between the IC(50)s of apamin
      (0.45 nM) and methyl-laudanosine (1.8 microM) in SK3 cells was essentially due to
      a major difference in their k(-1) (0.028 s(-1) for apamin and >or=20 s(-1) for
      methyl-laudanosine). These experiments demonstrate that both methyl-laudanosine
      and methyl-noscapine are medium potency, quickly dissociating, SK channel
      blockers with a similar potency on the three SK subtypes. Methyl-noscapine may be
      superior in terms of specificity for the SK channels.

PMID- 15504759
TI  - A novel Na+ channel agonist, dimethyl lithospermate B, slows Na+ current
      inactivation and increases action potential duration in isolated rat ventricular
      myocytes.
AB  - Voltage-gated Na(+) channel blockers have been widely used as local anaesthetics
      and antiarrhythmic agents. It has recently been proposed that Na(+) channel
      agonists can be used as inotropic agents. Here, we report the identification of a
      natural substance that acts as a Na(+) channel agonist. Using the patch-clamp
      technique in isolated rat ventricular myocytes, we investigated the
      electrophysiological effects of the substances isolated from the root extract of
      Salvia miltiorrhiza, which is known as 'Danshen' in Asian traditional medicine.
      By the intensive activity-guided fractionation, we identified dimethyl
      lithospermate B (dmLSB) as the most active component, while LSB, which is the
      major component of the extract, showed negligible electrophysiological effect.
      Action potential duration (APD(90)) was increased by 20 microM dmLSB from 58.8 +/
      12.1 to 202.3 +/- 9.5 ms. In spite of the prolonged APD, no early after
      depolarization (EAD) was observed. dmLSB had no noticeable effect on K(+) or
      Ca(2+) currents, but selectively affected Na(+) currents (I(Na)). dmLSB slowed
      the inactivation kinetics of I(Na) by increasing the proportion of slowly
      inactivating component without inducing any persistent I(Na). The relative
      amplitude of slow component compared to the peak fast I(Na) was increased dose
      dependently by dmLSB (EC(50) = 20 microM). Voltage dependence of inactivation was
      not affected by dmLSB, while voltage dependence of activation shifted by 5 mV to
      the depolarised direction. Since the APD prolongation by dmLSB did not provoke
      EAD, which is thought as a possible mechanism for the proarrhythmia seen in other
      Na(+) channel agonists, dmLSB might be an excellent candidate for a Na(+) channel
      agonist.

PMID- 15504760
TI  - Inhibitory effect of BIBN4096BS on cephalic vasodilatation induced by CGRP or
      transcranial electrical stimulation in the rat.
AB  - Calcitonin gene-related peptide (CGRP) is believed to play a pivotal role in the
      pathogenesis of migraine via activation of CGRP receptors in the
      trigeminovascular system. The CGRP receptor antagonist, BIBN4096BS, has proven
      efficacy in the acute treatment of migraine attacks and represents a new
      therapeutic principle. We used an improved closed cranial window model to measure
      changes of the middle meningeal artery (MMA) and cortical pial artery/arteriole
      diameter (PA) and changes in local cortical cerebral blood flow (LCBF(Flux)) in
      anaesthetised artificially ventilated rats. The ability of BIBN4096BS (i.v.) to
      prevent the vasodilatatory actions of rat-alphaCGRP, betaCGRP and endogenously
      released CGRP following transcranial electrical stimulation (TES) was
      investigated. BIBN4096BS was per se without vasoactive effect on any of the
      measured variables and significantly inhibited the hypotension induced by both
      types of CGRP (P < 0.001). The alphaCGRP induced MMA dilatation was reduced from
      97.4 +/- 14 to 2.1 +/- 1.3% (P < 0.001) and the betaCGRP induced dilatation was
      fully blocked by BIBN4096BS. ID(50) was 5.4 +/- 1.6 microg kg(-1) for alphaCGRP
      and 16.3 +/- 1.6 microg kg(-1) for betaCGRP. Transcranial electrical stimulation
      induced a 119.1 +/- 6.9% increase in MMA diameter. BIBN4096BS (333 microg kg(-1))
      attenuated this increase (19.8 +/- 2.1%) (P < 0.001). Systemic CGRP and TES
      induced an increase in PA diameter that was not significantly inhibited by
      BIBN4096BS. The CGRP induced increase in LCBF(Flux) was similar not prevented by
      the antagonist. We suggest that systemic BIBN4096BS exerts its inhibitory action
      mainly on large dural blood vessels (MMA).

PMID- 15504761
TI  - Staphylococcal enterotoxins condition cells of the innate immune system for Toll
      like receptor 4 stimulation.
AB  - In this report we examined overlap between superantigen (SAg) and Toll-like
      receptor 4 (TLR4) stimulation of the innate immune system. Before in vivo
      stimulation we found that mouse splenic DCs expressed unexpectedly low levels of
      surface TLR4 compared to macrophages. In response to LPS, TLR4 gene expression in
      fractionated spleen cells was downregulated. By comparison, surface TLR4 staining
      with the Sa15-21 mAb showed little downregulation, and the anti-TLR4 MTS510 mAb
      showed decreased staining, suggesting that LPS was bound to TLR4 at the time
      points examined. Interestingly, SAg stimulation induced decreased TLR4 staining
      as measured by the MTS510 mAb, even though the TLR4 gene was not downregulated.
      Nevertheless, LPS potently induced DCs to produce TNF and IL-12, but SAg did not,
      even though they efficiently activated DCs. Notwithstanding, in vivo stimulation
      with staphylococcal enterotoxin SAg conditioned the innate immune system to hyper
      respond to various pathogen-associated molecular patterns (PAMPs). Specifically,
      pre-priming with SAg enhanced LPS-mediated DC synthesis of TNF and IL-12. Thus,
      SAgs may exert their pathogenesis on the host by conditioning DCs, in a T cell
      activation dependent manner to potentiate responses to PAMPs.

PMID- 15504762
TI  - NF-kappaB elements associated with the Stat6 site in the germline gamma1
      immunoglobulin promoter are not necessary for the transcriptional response to
      CD40 ligand.
AB  - Both germline transcription and switch recombination of heavy chain genes are
      likely to be regulated by cis elements binding transcription factors in the
      promoter regions of germline immunoglobulin genes. To identify cis-acting
      elements important in germline transcription of the murine gamma1 heavy chain
      gene, we have used a transgenic approach. Seventeen kb gamma1 immunoglobulin
      transgenes with mutations in three NF-kappaB sites in the gamma1 proximal
      promoter, a putative CD40 response element, are expressed well. Compared to wild
      type transgenes, there is no deficiency in the expression of the transgenes with
      mutations of the three NF-kappaB sites after induction of splenic B cells with IL
      4 alone, CD40L, or CD40L + IL-4. There may be a small reduction in the response
      of these mutant transgenes after induction with LPS + IL-4. We also prepared
      transgenes that were truncated at -150 (rather than -2100) and therefore included
      the wild-type Stat6 binding site at -123 and the three wild-type NF-kappaB sites.
      Nevertheless, gamma1 germline transcripts were not expressed from these
      transgenes. We conclude that the three proximal NF-kappaB sites are dispensable
      for expression of gamma1 germline transcripts under most conditions. However, cis
      acting elements distal to -150 must be critical to this transcription.

PMID- 15504763
TI  - Community pulmonary rehabilitation after hospitalisation for acute exacerbations
      of chronic obstructive pulmonary disease: randomised controlled study.
AB  - OBJECTIVE: To evaluate the effects of an early community based pulmonary
      rehabilitation programme after hospitalisation for acute exacerbations of chronic
      obstructive pulmonary disease (COPD). DESIGN: A single centre, randomised
      controlled trial. SETTING: An inner city, secondary and tertiary care hospital in
      London. PARTICIPANTS: 42 patients admitted with an acute exacerbation of COPD.
      INTERVENTION: An eight week, pulmonary rehabilitation programme for outpatients,
      started within 10 days of hospital discharge, or usual care. MAIN OUTCOME
      MEASURES: Incremental shuttle walk distance, disease specific health status (St
      George's respiratory questionnaire, SGRQ; chronic respiratory questionnaire, CRQ)
      and generic health status (medical outcomes short form 36 questionnaire, SF-36)
      at three months after hospital discharge. RESULTS: Early pulmonary
      rehabilitation, compared with usual care, led to significant improvements in
      median incremental shuttle walk distance (60 metres, 95% confidence interval 26.6
      metres to 93.4 metres, P = 0.0002), mean SGRQ total score (-12.7, -5.0 to -20.3,
      P = 0.002), all four domains of the CRQ (dyspnoea 5.5, 2.0 to 9.0, P = 0.003;
      fatigue 5.3, 1.9 to 8.8, P = 0.004; emotion 8.7, 2.4 to 15.0, P = 0.008; and
      mastery 7.5, 4.2 to 10.7, P < 0.001) and the mental component score of the SF-36
      (20.1, 3.3 to 36.8, P = 0.02). Improvements in the physical component score of
      the SF-36 did not reach significance (10.6, -0.3 to 21.6, P = 0.057). CONCLUSION:
      Early pulmonary rehabilitation after admission to hospital for acute
      exacerbations of COPD is safe and leads to statistically and clinically
      significant improvements in exercise capacity and health status at three months.

PMID- 15504764
TI  - Academic health centers: sustaining the vision.

PMID- 15504765
TI  - Selling off or selling out? Medical schools and ethical leadership in tobacco
      stock divestment.
AB  - Medical and health science schools occupy a prestigious place in U.S. society.
      When they express a position on tobacco use--either by action or silence--that
      expression is consequential. Recognizing this, the tobacco industry has worked to
      sustain and exploit relationships with academic health sciences institutions.
      Corporate contributions to medical research are more visible, but institutional
      investments in tobacco stocks are also crucial to these relationships. The
      American Medical Association divested (sold) its tobacco holdings in 1986, urging
      others to do the same. Yet, as late as 2004, at least five of the leading dozen
      medical schools have not divested, and those that have seem reluctant to
      publicize their actions. The authors use internal tobacco industry documents and
      secondary source material to describe and analyze Philip Morris's response to two
      cases of threatened academic divestment. In each case, the world's largest
      tobacco company succeeded in minimizing the impact of divestment activities--in
      the first, by muting the consequences of a divestment, and in the second, by
      convincing university decisionmakers to recommend against tobacco stock
      divestment. In addition to arguing that tobacco divestment would lead to other
      pressures or be ineffective, the company exploited university concerns about
      losing corporate research funding as a key element of its antidivestment
      strategy. If academic medical centers regard protection of the public's health as
      a primary mission, divestment from tobacco holdings is essential; profiting from
      tobacco either through investments or research funding undermines this mission.
      Silent divestment squanders opportunities for ethical leadership and public
      dialogue.

PMID- 15504766
TI  - Making history: lessons from the great moments series of pharmaceutical
      advertisements.
AB  - The authors shed light on present-day pharmaceutical advertisements by looking
      back to an important early chapter in pharmaceutical company-sponsored promotion:
      the Great Moments in Medicine and Great Moments in Pharmacy, a series of
      commercial paintings produced by Parke, Davis & Company between 1948 and 1964.
      Beginning in the early 1950s, Parke-Davis delivered reproductions of the Great
      Moments images to physicians and pharmacies throughout the United States and
      Canada and funded monthly pullout facsimiles in key national magazines. The
      images also appeared in calendars, popular magazines, and "educational"
      brochures. By the mid-1960s, articles in both the popular and the medical press
      lauded the Great Moments for "changing the face of the American doctor's office"
      while describing the painter, Robert Thom, as the "Norman Rockwell" of medicine.
      The authors' brief analysis uses source material including popular articles about
      the Great Moments, existing scholarship, previously unexamined artist's notes,
      and, ultimately, the images themselves to explain why these seemingly kitschy
      paintings attained such widespread acclaim. They show how the Great Moments
      tapped into a 1950s medical climate when doctors were thought of as powerfully
      independent practitioners, pharmaceutical companies begged the doctor's good
      graces, and HMOs and health plans were nowhere to be seen. The authors conclude
      by suggesting that the images offer important lessons for thinking about the many
      pharmaceutical advertisements that confront present-day doctors, patients, and
      other consumers.

PMID- 15504767
TI  - Using the literature in developing McGill's guidelines for interactions between
      residents and the pharmaceutical industry.
AB  - Evidence suggests that the pharmaceutical industry exerts a large influence on
      residents' education and practice. Yet existing guidelines by professional bodies
      do not cover the specifics of residents' interactions with the pharmaceutical
      industry. At the psychiatry residency program of the McGill University Health
      Center, the authors set out to systematically evaluate areas of concern for
      residents and to develop guidelines for use by residents during and outside their
      training. Areas of concern included educational activities, training,
      fundraising, and other specific resident-industry interactions. In 1998, a
      committee of residents and faculty systematically evaluated areas of concern and,
      based on a review of the literature and discussions with experts, in 2000
      developed guidelines for use by McGill's psychiatry program residents. The
      process for guideline development and methods for their implementation in 2001
      are described. Education and training of residents on resident-industry
      interactions were included early in the curriculum. Guidelines were developed to
      address limitations on fundraising activities; restriction of direct gifts to
      residents; the appropriateness and awarding of industry fellowships; and the
      handling of drug samples, meals, and other presentations to residents. While
      guidelines for residents are useful adjuncts for guiding residents' interactions
      with the pharmaceutical industry, the authors conclude that they need to be
      reinforced with education and sensitization by faculty.

PMID- 15504768
TI  - Medical students' exposure to pharmaceutical industry marketing: a survey at one
      U.S. medical school.
AB  - PURPOSE: While much is known about the interactions between the pharmaceutical
      industry and physicians, very little is known about pharmaceutical marketing
      directed toward medical students. This study sought to characterize the extent
      and forms of medical students' exposure to pharmaceutical industry marketing.
      METHOD: In 2001-02, an anonymous, 17-item questionnaire was distributed to 165
      preclinical and 116 clinical students at the University of Minnesota Medical
      School-Twin Cities. The main outcome measures were the number and forms of
      exposures to pharmaceutical industry marketing reported by medical students and
      whether students had discussed these exposures with teachers or advisors.
      Preclinical and clinical students were compared using chi(2) analysis (p < .05).
      RESULTS: One hundred fourteen (69.1%) preclinical students and 107 (92.2%)
      clinical students responded. Nearly all students reported at least one exposure
      to pharmaceutical industry marketing. Seventy-six (71.7%) clinical students
      compared to 38 (33.3%) preclinical students recalled over 20 exposures (p <
      .005). Clinical students were more likely to have received a free meal (p < .01),
      textbook (p < .005), pocket text (p < .005), or trinket (p < .005) than were
      their preclinical colleagues. Most students (68.2%) had not discussed
      pharmaceutical marketing with an instructor or advisor; 59 (55.7%) clinical
      students as compared to 87 (80.6%) preclinical students recalled no such
      discussion (p < .005). CONCLUSION: Medical students have extensive exposure to
      pharmaceutical industry marketing during their early years of training. Given
      existing evidence that such exposure influences physicians' practice and
      prescribing patterns, the authors propose that medical school curricula include
      formal instruction to prepare students to critically assess these contacts.

PMID- 15504769
TI  - A prospective before-and-after trial of an educational intervention about
      pharmaceutical marketing.
AB  - PURPOSE: There is increasing evidence that physicians may be compromised by their
      interactions with the pharmaceutical industry. The authors aimed to develop and
      determine the effect of an educational intervention to inform family medicine
      residents about pharmaceutical marketing. METHOD: Confidential, self-administered
      questionnaires were administered to family medicine residents at McMaster
      University, Hamilton, Canada, immediately before and after a two-part, 2.5-hour
      educational intervention. The curriculum consisted of (1) a faculty-led debate
      and discussion of a systematic review of physician-pharmaceutical industry
      interactions, and (2) an interactive workshop that included a presentation
      highlighting key empirical findings, a video illustrating techniques to optimize
      pharmaceutical sales representatives' visits, and small- and large-group problem
      based discussions. Residents were asked about their attitudes toward five
      marketing strategies: drug samples, industry-sponsored continuing medical
      education, one-on-one interactions with sales representatives, free meals, and
      gifts worth less than CAN $10. RESULTS: A total of 37 residents responded to both
      questionnaires. After the intervention residents had more cautious attitudes,
      rating marketing strategies on a five-point Likert scale as less ethically
      appropriate (-0.41, p < .05) and less valuable to patients or useful to the
      resident (-0.39, p < .05), and reporting less intention to use them in the future
      (-0.44, p < .01). CONCLUSION: This intervention appears to have promoted more
      cautious attitudes toward pharmaceuticals marketing. Its long-term sustainability
      and effect on behavior remain unknown.

PMID- 15504770
TI  - Faculty ownership of medical facilities: inappropriate conflict or an opportunity
      that benefits physicians and patients?
AB  - As a result of a confluence of issues, including faculty compensation in an
      academic health center (AHC), increasing awareness of conflict-of-interest
      issues, growing interest by faculty in entrepreneurial activities, and the
      creation of numerous new facilities and buildings associated with the AHC, the
      Indiana University School of Medicine (IUSM) in Indianapolis addressed the
      question of whether its faculty or even faculty groups could invest in any of
      these new entities, either as individuals or as groups. The dean of IUSM
      appointed a subcommittee of the school's standing Conflict of Interest Committee
      that included distinct groups of stakeholders and those without any fiduciary
      interests. As a result of meetings of this subcommittee, a new policy was set
      forth in a Points to Consider document to meet the emerging needs of the school
      to deal with such issues. The authors present the policy and the deliberations
      leading up to it as an example of how to address the issue of faculty ownership
      of medical facilities.

PMID- 15504771
TI  - An ethical framework for identifying, preventing, and managing conflicts
      confronting leaders of academic health centers.
AB  - Leaders of academic health centers (AHCs) hold positions that by their very
      nature have a high potential for ethical conflict. The authors offer an ethical
      framework for identifying, preventing, and managing conflicts in the leadership
      of AHCs. This framework is based on and implements both the ethical concept of
      AHCs as fiduciary organizations and also the legitimate interests of various
      stakeholders. The authors describe practical steps that can be tools for the
      preventive-ethics leadership of AHCs that enable leaders to avoid strategic
      ambiguity and strategic procrastination and replace these with transparency. The
      ethical framework is illustrated by applying it to an organizational case study.
      The major contribution of the ethical framework is that it transforms decision
      making from simply negotiating power struggles to explicitly identifying and
      making ethical decisions based on the legitimate interests and fiduciary
      responsibilities of all stakeholders.

PMID- 15504773
TI  - The value of systematic reviews as research activities in medical education.
AB  - Medical residents and postdoctoral fellows are often required to conduct and
      publish original research as part of their medical education. However, their
      relative lack of experience, time, money, and sometimes supervision in conducting
      original research often results in research of modest quality on topics of
      limited importance. Such research may also consume scarce resources from the
      sponsoring institution. Manuscripts describing such research are often
      unremarkable, although most are submitted for publication, where editors and peer
      reviewers will spend time evaluating them. Systematic reviews of the literature,
      however, offer similar training in the scientific method, are relatively
      inexpensive to conduct, teach critical appraisal of the literature, give trainees
      a thorough command of the topic studied, and provide even new investigators the
      opportunity to make important contributions to the literature. Systematic reviews
      of the literature should thus be acceptable alternatives to original research
      assignments for most trainees in medical education programs. The author reviews
      the characteristics of systematic reviews, outlines the steps in conducting them,
      identifies the lessons learned from completing each step, and compares the
      advantages and disadvantages of systematic reviews with those of conducting
      original research.

PMID- 15504772
TI  - Developing resources to teach and assess the core competencies: a collaborative
      approach.
AB  - Graduate medical education programs face new challenges as they seek to comply
      with the mandate from the Accreditation Council on Graduate Medical Education to
      demonstrate that they are teaching and assessing residents on the six core
      competencies. The authors describe a project designed as a collaborative venture
      between the American Academy of Allergy, Asthma, and Immunology (AAAAI) and the
      Center for Educational Outcomes at Dartmouth College (CEdO) to provide residency
      programs in allergy/immunology with resources for teaching and assessing the core
      competencies. The goal was to create a set of learning and assessment resources
      that maximized the content knowledge expertise provided by the AAAAI and the
      learning expertise provided by CEdO. A highly interactive, iterative process was
      used to create a set of Web-based modules. Bilateral communication, buy-in, and
      active involvement in the process were seen as crucial to the development of
      resources and their successful implementation. Approximately 18 months after the
      modules were made available to training program directors, 80% of the directors
      surveyed were aware of and had accessed the modules. The joint creation process
      used in this project, designed to be generally applicable across specialties,
      reveals how the burden of meeting new requirements can be decreased when experts
      in content knowledge and experts in learning collaborate.

PMID- 15504774
TI  - Weaving basic and social sciences into a case-based, clinically oriented medical
      curriculum: one school's approach.
AB  - Southern Illinois University School of Medicine recently completed its fourth
      year of a resource-session-enhanced, case-based, tutor-group-oriented curriculum.
      As an example of a curricular unit, the authors describe the implementation of
      the basic and clinical sciences in one of the four units in year one, and detail
      that unit's organization, logistics, content, rationale, and other
      characteristics. The Sensorimotor Systems and Behavior (SSB) unit is preceded by
      a cardio-respiratory-renal unit and is followed by an endocrine-reproductive
      gastrointestinal unit. A Doctoring unit temporally spans each of these three
      units. The SSB unit is allotted an 11.5-week period that includes an aggregate of
      2.5 weeks of available clinical time, 1.5 weeks for examinations and exam study
      time, and approximately 8.5 weeks for tutor-group sessions, mandatory laboratory
      sessions, and self-directed learning. Optional resource sessions are offered
      during a two- to four-hour block on a single morning each week. Clinical training
      in the SSB unit augments self-directed, laboratory, and tutor-group learning of
      neuroscience, gross anatomy, cell biology, physiology, biochemistry, behavioral
      and social science, embryology, limited pharmacology and genetics, and basic
      clinical neurology for first-year students. Although it is fast-paced and places
      heavy responsibility for independent learning on the students, the SSB unit
      culminates in significant achievement in the basic and clinical sciences. The
      unit provides substantial clinical training and practical experience in physical
      and neurological examinations that directly integrate with basic science
      knowledge. The unit reduces lecture-based instruction, demands self
      determination, and promotes experience in team effort, professionalism, peer
      interaction, empathy in clinical medicine, and practical use of basic science
      knowledge.

PMID- 15504777
TI  - A story that illustrates humanism in medicine: Humanity--lost and found.

PMID- 15504778
TI  - Assessing the teaching behaviors of ambulatory care preceptors.
AB  - PURPOSE: Medical educators are increasingly concerned about the quality of skills
      instruction at medical schools in the United States, yet few data exist to
      support quality assessment and faculty development. The purpose of this research
      was to (1) develop an instrument for measuring teaching behavior of ambulatory
      care preceptors (the Teaching Encounter Card), and (2) assess current teaching
      practices at one institution. METHOD: Based on published guidelines for teaching
      in the ambulatory setting, the authors identified nine teaching behaviors for
      inclusion on a Teaching Encounter Card. Students completed the card immediately
      after a supervised patient (teaching) encounter, indicating (yes/no) if they
      observed each behavior. Validation of the card was assessed using standardized
      patients and scripted teaching encounters. A field application of the card
      assessed behaviors for 17 preceptors and 270 teaching encounters in one
      ambulatory care clerkship. RESULTS: Validation testing revealed the card was
      highly accurate. Specificity exceeded 75% for all behaviors and sensitivity
      exceeded 75% for eight. During the field application, preceptors used each of the
      behaviors except three in over 70% of encounters. The three exceptions were
      observing the student interviewing or counseling (68% of encounters), providing
      feedback (52% of encounters), and observing the student perform any part of the
      physical examination (24% of encounters). Interpreceptor variability was
      substantial for several behaviors. CONCLUSIONS: The Teaching Encounter Card is
      valid and represents a new tool for quality assessment and faculty development.
      Preceptors and course directors will need guidelines or educational standards to
      help them interpret individual results.

PMID- 15504779
TI  - The views of U.S. medical school deans toward academic primary care.
AB  - PURPOSE: To understand the views of U.S. medical school deans about their primary
      care faculties. METHOD: In 2000, the authors mailed a questionnaire containing 43
      multipart items to deans of 130 U.S. allopathic medical schools. The
      questionnaire assessed the deans' attitudes about and evaluation of primary care
      at their school and their school's efforts to strengthen it. Deans were asked to
      compare family medicine, general internal medicine, and general pediatrics with
      nonprimary care clinical departments at their schools. RESULTS: Of the 83 (64%)
      deans who responded, 82% reported their school had departments or divisions of
      family medicine, general internal medicine, and general pediatrics. Deans rated
      general internal medicine and general pediatrics higher than nonprimary care
      faculty on clinical expertise and productivity (p < .001) and family medicine
      equivalent to nonprimary care faculty. Deans rated all three primary care
      faculties superior to nonprimary care faculty for teaching skills (p < .001) and
      programs (p < .05), but lower than nonprimary care disciplines for research
      productivity (p < .01) and revenues (p < .001). They rated family medicine and
      general pediatrics lower for research skills (p < .001), but 73% of deans stated
      research was equally important for primary care and nonprimary care departments.
      Deans considered overall financial resources to be equivalent for primary care
      and nonprimary care departments, but 77% of deans felt primary care departments
      or divisions needed financial support from the medical school to survive. Most
      deans attempted to strengthen primary care by changing the curriculum to promote
      primary care and by providing financial support. CONCLUSIONS: Deans ranked
      primary care faculty high on clinical and teaching measures. Although they
      considered research to be an important activity for primary care faculty, they
      evaluated it low relative to nonprimary care departments.

PMID- 15504780
TI  - Perspective.

PMID- 15504781
TI  - Do volunteer community-based preceptors value students' feedback?
AB  - PURPOSE: A key component of educational practice is to provide feedback and
      evaluation to teachers and learners to improve the teaching and learning process.
      The purpose of this study was to determine whether volunteer community preceptors
      value evaluation and feedback by students as much as they value other resources
      or rewards. METHOD: In Fall 1999, a questionnaire concerning the resources and
      rewards of preceptorship was mailed to 236 community preceptors affiliated with
      the Mercer University School of Medicine, Macon, Georgia. Preceptors were asked
      to rate 20 factors on a five-point Likert scale (5 = very important to 1 = not
      very important). The mean values were compared using t-tests. RESULTS: One
      hundred sixty-eight preceptors (71%) completed questionnaires. Preceptors rated
      evaluation and feedback from students significantly higher (p < .001) than all
      other factors (mean = 4.02, standard deviation [SD] = .87). Continuing medical
      education for teaching was the next most highly valued factor (mean = 3.67, SD =
      1.14). Preceptors rated financial compensation the lowest (mean = 2.01, SD =
      1.19) of all factors. The high rank of feedback and evaluation from students
      persisted across gender, specialty, length of time as a preceptor, practice
      location, and years practicing medicine. CONCLUSION: This study demonstrates that
      feedback and evaluation from students is highly valued. The knowledge that
      community-based preceptors highly value feedback and evaluation from students
      should stimulate medical school programs to provide feedback and evaluation to
      preceptors that will enhance the educational outcomes for both faculty and
      learners.

PMID- 15504782
TI  - U.S. and Canadian internal medicine clerkship directors' opinions about teaching
      procedural and interpretive skills to medical students.
AB  - PURPOSE: Although medical students gain experience in performing procedures
      during their clinical clerkships, which skills they should acquire remains
      unclear. The authors sought opinions from internal medicine clerkship directors
      regarding procedural and interpretive skills students should and do learn during
      clerkships. METHOD: In 2002, the 123 members of the Clerkship Directors in
      Internal Medicine (CDIM) were confidentially surveyed using a 79-item
      questionnaire about the appropriateness of 20 procedural skills, demographics,
      clerkship characteristics, and curricula in procedural skills. Participants had
      the choice of completing a mailed paper questionnaire or an electronic version on
      the CDIM's Web site. After univariate analysis, adjusted comparisons among
      participants were made using linear regression. RESULTS: Surveys were completed
      by 89 clerkship directors (72%). Most thought that students should be taught 17
      of 20 procedural skills. However, the majority thought students do not learn five
      of these skills. Over 80% of respondents thought students should learn: chest x
      ray interpretation, electrocardiogram interpretation, phlebotomy, throat culture,
      blood culture, urinalysis, Pap smear, central line placement, peripheral blood
      smear. However, the majority thought students do not learn five of these skills.
      The mean of skills that should be taught and are learned were 15 (standard
      deviation [SD] = 3) and 12 (SD = 4), respectively. About half used formal
      teaching in procedures (44%), used logs (51%) and tested competency (45%).
      CONCLUSIONS: CDIM members thought medical students should be taught a variety of
      procedural skills but thought students fail to learn many. These findings may
      help prioritize which procedures to teach. It may be helpful to develop
      standardized curricular materials on teaching procedures.

PMID- 15504783
TI  - Misusing the moments.

PMID- 15504784
TI  - Handheld computer use in a family medicine clerkship.
AB  - PURPOSE: The objectives of this study were to track students' use of medical and
      nonmedical personal digital assistant (PDA) software and to obtain students'
      ratings of the usefulness of PDAs in a family medicine clerkship. METHOD: During
      the academic year 2001-02, third-year clerkship students at the Northeastern Ohio
      Universities College of Medicine were loaned PDAs equipped with company-installed
      software, such as a date book and address book. Additional software was installed
      (Griffith's 5 Minute Clinical Consult, ePocrates qRx, ePocrates qID, iSilo,
      HanDBase, MedCalc, and Application Usage). Pre- and post-orientation
      questionnaires and a post-rotation evaluation measured students' comfort level,
      the perceived usefulness, and ratings of programs on their PDA. Application Usage
      tracked the number of minutes and times students used each software program.
      RESULTS: Eighty-five students completed the study. They rated ePocrates qRx and
      Griffith's 5 Minute Clinical Consult the most useful medical software programs.
      PDAs were rated as "almost always" enhancing the clerkship experience. Students
      reported the PDA altered the way they accessed clinical information and that
      every few days it helped them understand a clinical discussion. Experience with
      computer technology was correlated with PDA use. CONCLUSIONS: This study
      objectively demonstrates clerkship students' use of PDA resources. Students' use
      mirrors their assessment of the value of the software. Although PDAs and software
      programs can be an expense, it is a worthwhile educational resource as evaluated
      by the medical student.

PMID- 15504785
TI  - Assessing the relationship of learning approaches to workplace climate in
      clerkship and residency.
AB  - PURPOSE: To determine what approaches to learning are adopted by clinical clerks
      and residents and whether these approaches are associated with demographic
      factors, specialty, level of training, and perceptions of the workplace climate.
      METHOD: In 2001-02, medical clerks (n = 532) and residents (n = 2,939) at five
      medical schools in Ontario, Canada, were mailed the Workplace Learning
      Questionnaire. The correlation between the approaches to learning at work and
      perceived workplace climate and the influence of gender, age, location, residency
      program and level of training on outcomes were measured. RESULTS: A total of
      1,642 clerks and residents responded (47%). The factor structure and reliability
      of the Workplace Learning Questionnaire were confirmed for these respondents. A
      surface-disorganized approach to learning was correlated with perception of heavy
      workload (r = .401, p < .001). The deep approach to learning was correlated with
      perception of choice-independence in the workplace and a supportive-receptive
      workplace (r = .32, p < .001; r = .23, p < .001). The climate factors, perception
      of choice-independence and supportive-receptive workplace, were correlated (r =
      .60, p < .001). There were significant differences among the mean scores for
      scales based on residency, year of training, and location of training.
      CONCLUSIONS: Perception of the workplace climate was associated with the approach
      to learning in the workplace of clerks and residents. Perception of heavy
      workload was associated with less effective approaches to learning. These
      associations varied with the residency program and the level of training.

PMID- 15504786
TI  - Evidence-based medicine: ethically obligatory or ethically suspect?

PMID- 15504787
TI  - Response to Dr. Gupta.

PMID- 15504788
TI  - The worm turns: publication bias and trial registers revisited.

PMID- 15504789
TI  - Duration of untreated psychosis significantly associated with positive symptoms
      one year after treatment.

PMID- 15504790
TI  - Acute stress disorder is of limited benefit in predicting post-traumatic stress
      disorder in people surviving traumatic injury.

PMID- 15504791
TI  - Psychological function is mildly impaired for prolonged periods before and after
      first unipolar major depressive episode.

PMID- 15504792
TI  - Review: in people with schizophrenia, lithium is ineffective as sole therapy,
      while evidence on augmenting antipsychotics with lithium is inconclusive.

PMID- 15504793
TI  - Cognitive behavioural therapy improves psychotic symptoms at 18 months in people
      with schizophrenia.

PMID- 15504794
TI  - Review: high doses of antipsychotic drugs are no more or less effective than
      medium doses in people with schizophrenia.

PMID- 15504795
TI  - Review: combining pindolol with an SSRI improves early outcomes in people with
      depression.

PMID- 15504796
TI  - Review: antidepressants are moderately effective in people with depression and a
      substance dependence disorder.

PMID- 15504797
TI  - Review: St John's Wort may be less effective than previously thought in people
      with depression.

PMID- 15504798
TI  - PEARLS home based treatment significantly improves depression, dysthymia, and
      health related quality of life in older people.

PMID- 15504800
TI  - Donepezil did not reduce the rate of institutionalisation or disability in people
      with mild to moderate Alzheimer's disease.

PMID- 15504799
TI  - Withdrawing neuroleptic treatment from people with dementia, does not result in a
      significant change to their behaviour, psychiatric symptoms, or quality of life.

PMID- 15504801
TI  - Trauma focused cognitive behavioural therapy reduces PTSD more effectively than
      child centred therapy in children who have been sexually abused.

PMID- 15504802
TI  - Switching serotonin reuptake inhibitors may be of benefit in people with
      obsessive compulsive disorder.

PMID- 15504803
TI  - Review: relying on published data alone overestimates efficacy and safety of
      SSRIs in children.

PMID- 15504804
TI  - Increasing a partner's understanding of motherhood significantly reduces
      postnatal distress and depression in first time mothers with low self esteem.

PMID- 15504805
TI  - Integrative Behavioral Couple Therapy is as effective as Traditional Behavioral
      Couple Therapy for distressed couples.

PMID- 15504806
TI  - Cognitive behavioural therapy significantly improves hypochondriacal symptoms.

PMID- 15504808
TI  - Concomitant loop diuretics and ACE inhibitors increase risk of lithium toxicity
      in elderly people.

PMID- 15504807
TI  - Review: current evidence does not show a strong causal relation between the use
      of cannabis in young people and psychosocial harm.

PMID- 15504809
TI  - Externalising problems and environmental stressors predict adolescent problems in
      children from divorced families.

PMID- 15504810
TI  - Individuals with opioid dependence who leave drug treatment have higher overdose
      and death rates than those still in treatment.

PMID- 15504811
TI  - Depressive disorders were the fourth leading cause of global disease burden in
      the year 2000.

PMID- 15504812
TI  - Personality disorders commonly occur in people with alcohol and drug use
      disorders.

PMID- 15504813
TI  - Sleepiness, sleep apnea, and driving: still miles to go before we safely sleep.

PMID- 15504814
TI  - Lung injury: sphingosine-1-phosphate to the rescue.

PMID- 15504815
TI  - Smoke and mirrors: Mouse models as a reflection of human chronic obstructive
      pulmonary disease.

PMID- 15504816
TI  - Obliterative bronchiolitis after lung transplantation: a repetitive multiple
      injury airway disease.

PMID- 15504818
TI  - Patient outcome of invasive experiments.

PMID- 15504819
TI  - Inhibition of phosphatidylserine recognition heightens the immunogenicity of
      irradiated lymphoma cells in vivo.
AB  - Strategies to enhance the immunogenicity of tumors are urgently needed. Although
      vaccination with irradiated dying lymphoma cells recruits a tumor-specific immune
      response, its efficiency as immunogen is poor. Annexin V (AxV) binds with high
      affinity to phosphatidylserine on the surface of apoptotic and necrotic cells and
      thereby impairs their uptake by macrophages. Here, we report that AxV
      preferentially targets irradiated lymphoma cells to CD8+ dendritic cells for in
      vivo clearance, elicits the release of proinflammatory cytokines and dramatically
      enhances the protection elicited against the tumor. The response was endowed with
      both memory, because protected animals rejected living lymphoma cells after 72 d,
      and specificity, because vaccinated animals failed to reject unrelated neoplasms.
      Finally, AxV-coupled irradiated cells induced the regression of growing tumors.
      These data indicate that endogenous adjuvants that bind to dying tumor cells can
      be exploited to target tumors for immune rejection.

PMID- 15504820
TI  - Immunoglobulin class switch recombination is impaired in Atm-deficient mice.
AB  - Immunoglobulin class switch recombination (Ig CSR) involves DNA double strand
      breaks (DSBs) at recombining switch regions and repair of these breaks by
      nonhomologous end-joining. Because the protein kinase ataxia telengiectasia (AT)
      mutated (ATM) plays a critical role in DSB repair and AT patients show
      abnormalities of Ig isotype expression, we assessed the role of ATM in CSR by
      examining ATM-deficient mice. In response to T cell-dependent antigen (Ag), Atm-/
      mice secreted substantially less Ag-specific IgA, IgG1, IgG2b, and IgG3, and
      less total IgE than Atm+/+ controls. To determine whether Atm-/- B cells have an
      intrinsic defect in their ability to undergo CSR, we analyzed in vitro responses
      of purified B cells. Atm-/- cells secreted substantially less IgA, IgG1, IgG2a,
      IgG3, and IgE than wild-type (WT) controls in response to stimulation with
      lipopolysaccharide, CD40 ligand, or anti-IgD plus appropriate cytokines.
      Molecular analysis of in vitro responses indicated that WT and Atm-/- B cells
      produced equivalent amounts of germline IgG1 and IgE transcripts, whereas Atm-/-
      B cells produced markedly reduced productive IgG1 and IgE transcripts. The
      reduction in isotype switching by Atm-/- B cells occurs at the level of genomic
      DNA recombination as measured by digestion-circularization PCR. Analysis of
      sequences at CSR sites indicated that there is greater microhomology at the mu
      gamma1 switch junctions in ATM B cells than in wild-type B cells, suggesting that
      ATM function affects the need or preference for sequence homology in the CSR
      process. These findings suggest a role of ATM in DNA DSB recognition and/or
      repair during CSR.

PMID- 15504821
TI  - Important roles for E protein binding sites within the immunoglobulin kappa chain
      intronic enhancer in activating Vkappa Jkappa rearrangement.
AB  - The immunoglobulin kappa light chain intronic enhancer (iEkappa) activates kappa
      rearrangement and is required to maintain the earlier or more efficient
      rearrangement of kappa versus lambda (lambda). To understand the mechanism of how
      iEkappa regulates kappa rearrangement, we employed homologous recombination to
      mutate individual functional motifs within iE(kappa) in the endogenous kappa
      locus, including the NF-kappaB binding site (kappaB), as well as kappaE1,
      kappaE2, and kappaE3 E boxes. Analysis of the impacts of these mutations revealed
      that kappaE2 and to a lesser extent kappaE1, but not kappaE3, were important for
      activating kappa rearrangement. Surprisingly, mutation of the kappaB site had no
      apparent effect on kappa rearrangement. Comparable to the deletion of the entire
      iEkappa, simultaneous mutation of kappaE1 and kappaE2 reduces the efficiency of
      kappa rearrangement much more dramatically than either kappaE1 or kappaE2
      mutation alone. Because E2A family proteins are the only known factors that bind
      to these E boxes, these findings provide unambiguous evidence that E2A is a key
      regulator of kappa rearrangement.

PMID- 15504822
TI  - Siderophore biosynthesis but not reductive iron assimilation is essential for
      Aspergillus fumigatus virulence.
AB  - The ability to acquire iron in vivo is essential for most microbial pathogens.
      Here we show that Aspergillus fumigatus does not have specific mechanisms for the
      utilization of host iron sources. However, it does have functional siderophore
      assisted iron mobilization and reductive iron assimilation systems, both of which
      are induced upon iron deprivation. Abrogation of reductive iron assimilation, by
      inactivation of the high affinity iron permease (FtrA), has no effect on
      virulence in a murine model of invasive aspergillosis. In striking contrast, A.
      fumigatus L-ornithine-N5-monooxygenase (SidA), which catalyses the first
      committed step of hydroxamate-type siderophore biosynthesis, is absolutely
      essential for virulence. Thus, A. fumigatus SidA is an essential virulence
      attribute. Combined with the absence of a sidA ortholog-and the fungal
      siderophore system in general-in mammals, these data demonstrate that the
      siderophore biosynthetic pathway represents a promising new target for the
      development of antifungal therapies.

PMID- 15504823
TI  - Loss of Bim increases T cell production and function in interleukin 7 receptor
      deficient mice.
AB  - Interleukin (IL)-7 receptor (R) signaling is essential for T and B lymphopoiesis
      by promoting proliferation, differentiation, and survival of cells. Mice lacking
      either IL-7 or the IL-7Ralpha chain have abnormally low numbers of immature as
      well as mature T and B lymphocytes. Transgenic expression of the apoptosis
      inhibitor Bcl-2 rescues T cell development and function in IL-7Ralpha-deficient
      mice, indicating that activation of a proapoptotic Bcl-2 family member causes
      death of immature and mature T cells. BH3-only proteins such as Bim, which are
      distant proapoptotic members of the Bcl-2 family, are essential initiators of
      programmed cell death and stress-induced apoptosis. We generated Bim/IL-7Ralpha
      double deficient mice and found that loss of Bim significantly increased
      thymocyte numbers, restored near normal numbers of mature T cells in the blood
      and spleen, and enhanced cytotoxic T cell responses to virus infection in IL
      7Ralpha-/- mice. These results indicate that Bim cooperates with other
      proapoptotic proteins in the death of IL-7-deprived T cell progenitors in vivo,
      but is the major inducer of this pathway to apoptosis in mature T cells. This
      indicates that pharmacological inhibition of Bim function might be useful for
      boosting immune responses in immunodeficient patients.

PMID- 15504824
TI  - Chloroquine resistance in Plasmodium vivax.

PMID- 15504825
TI  - In vitro testing of antimicrobial activity of bone cement.
AB  - The purpose of this study was to establish a reliable and cost-effective
      microplate proliferation assay for in vitro antimicrobial testing of bone cement
      samples. Cement samples devoid of antimicrobial agents, loaded with 2% gentamicin
      or with different concentrations of high-porosity silver, were incubated in a 96
      well microplate with several staphylococcal, Pseudomonas aeruginosa, and
      Enterococcus faecium isolates exhibiting different susceptibilities to
      gentamicin. After being rinsed, the samples were brought into a soy medium in
      which adherent cells on the cement surface either were killed by the
      antimicrobial surface or started to release clonal counterparts. The medium was
      monitored in real time by recording a time proliferation curve for each well.
      Microplate testing revealed no antibacterial effect of plain bone cement. The
      antibacterial activity of gentamicin-loaded bone cement was shown by the
      microplate test to depend on the gentamicin susceptibilities of the strains. The
      effect of high-porosity silver was dose dependent. Bactericidal activity against
      all tested strains was found for bone cement loaded with 1% high-porosity silver.
      The accuracy of this new proliferation assay was shown by the high correlation
      between the types of proliferation curves and antibiotic susceptibility. In
      contrast to routine agar diffusion testing, it assesses the dynamic response of
      microorganisms to antimicrobial agents in biomaterials and allows high-throughput
      screening and detection of antimicrobial properties of poorly water-soluble
      compounds like silver.

PMID- 15504826
TI  - Synergism between amodiaquine and its major metabolite, desethylamodiaquine,
      against Plasmodium falciparum in vitro.
AB  - The in vitro activity of the prodrug amodiaquine and its metabolite monodesethyl
      amodiaquine has been studied for three strains of Plasmodium falciparum: LS-2, LS
      3, and LS-1. Both compounds showed significant activity against all three
      strains; the activity of amodiaquine was slightly higher than that of the
      metabolite. By use of a checkerboard design, interaction studies with both
      compounds yielded evidence of significant synergism; means of the sums of the
      fractional inhibitory concentrations were 0.0392 to 0.0746 for strain LS-2,
      0.1567 to 0.3102 for strain LS-3, and 0.025 to 0.3369 for strain LS-1. In further
      investigations, the interaction of amodiaquine with monodesethyl-amodiaquine was
      tested at clinically relevant concentrations of both compounds. In these studies,
      involving amodiaquine at picomolar and femtomolar concentrations, the compound
      was found to exert high potentiating activity on monodesethyl-amodiaquine. This
      interaction produced mean ratios of observed to expected activity of 0.0505 to
      0.0642 for strain LS-2, 0.0882 to 0.3820 for strain LS-3, and 0.0752 to 0.2924
      for strain LS-1. The synergistic activity was most marked at monodesethyl
      amodiaquine/amodiaquine ratios up to 100,000:1 but was still evident at higher
      ratios.

PMID- 15504827
TI  - Modified fixed-ratio isobologram method for studying in vitro interactions
      between atovaquone and proguanil or dihydroartemisinin against drug-resistant
      strains of Plasmodium falciparum.
AB  - A modified fixed-ratio isobologram method for studying the in vitro interactions
      between antiplasmodial drugs is described. This method was used to examine the
      interactions between atovaquone, proguanil, and dihydroartemisinin. The
      interaction between atovaquone and proguanil was synergistic against atovaquone
      sensitive strains K1 and T996; however, there was a loss of synergy against
      atovaquone-resistant strain NGATV01 isolated after Malarone (the combination of
      atovaquone and proguanil) treatment failure. While the interaction between
      atovaquone and dihydroartemisinin was indifferent against isolate NGATV01, the
      interaction displayed indifference tending toward antagonism against the
      atovaquone-sensitive strains tested. The relevance of in vitro interactions to in
      vivo treatment is discussed.

PMID- 15504828
TI  - Antipneumococcal activities of two novel macrolides, GW 773546 and GW 708408,
      compared with those of erythromycin, azithromycin, clarithromycin, clindamycin,
      and telithromycin.
AB  - The MICs of GW 773546, GW 708408, and telithromycin for 164 macrolide-susceptible
      and 161 macrolide-resistant pneumococci were low. The MICs of GW 773546, GW
      708408, and telithromycin for macrolide-resistant strains were similar,
      irrespective of the resistance genotypes of the strains. Clindamycin was active
      against all macrolide-resistant strains except those with erm(B) and one strain
      with a 23S rRNA mutation. GW 773546, GW 708408, and telithromycin at two times
      their MICs were bactericidal after 24 h for 7 to 8 of 12 strains. Serial passages
      of 12 strains in the presence of sub-MICs yielded 54 mutants, 29 of which had
      changes in the L4 or L22 protein or the 23S rRNA sequence. Among the macrolide
      susceptible strains, resistant mutants developed most rapidly after passage in
      the presence of clindamycin, GW 773546, erythromycin, azithromycin, and
      clarithromycin and slowest after passage in the presence of GW 708408 and
      telithromycin. Selection of strains for which MICs were >/=0.5 microg/ml from
      susceptible parents occurred only with erythromycin, azithromycin,
      clarithromycin, and clindamycin; 36 resistant clones from susceptible parent
      strains had changes in the sequences of the L4 or L22 protein or 23S rRNA. No
      mef(E) strains yielded resistant clones after passage in the presence of
      erythromycin and azithromycin. Selection with GW 773546, GW 708408,
      telithromycin, and clindamycin in two mef(E) strains did not raise the
      erythromycin, azithromycin, and clarithromycin MICs more than twofold. There were
      no change in the ribosomal protein (L4 or L22) or 23S rRNA sequences for 15 of 18
      mutants selected for macrolide resistance; 3 mutants had changes in the L22
      protein sequence. GW 773546, GW 708408, and telithromycin selected clones for
      which MICs were 0.03 to >2.0 microg/ml. Single-step studies showed mutation
      frequencies <5.0 x 10(-10) to 3.5 x 10(-7) for GW 773546, GW 708408, and
      telithromycin for macrolide-susceptible strains and 1.1 x 10(-7) to >4.3 x 10(-3)
      for resistant strains. The postantibiotic effects of GW 773546, GW 708408, and
      telithromycin were 2.4 to 9.8 h.

PMID- 15504829
TI  - Activities of two novel macrolides, GW 773546 and GW 708408, compared with those
      of telithromycin, erythromycin, azithromycin, and clarithromycin against
      Haemophilus influenzae.
AB  - The MIC at which 50% of strains are inhibited (MIC(50)) and the MIC(90) of GW
      773546, a novel macrolide, were 1.0 and 2.0 microg/ml, respectively, for 223 beta
      lactamase-positive, beta-lactamase-negative, and beta-lactamase-negative
      ampicillin-resistant Haemophilus influenzae strains. The MIC(50)s and MIC(90)s of
      GW 708408, a second novel macrolide, and telithromycin, an established ketolide,
      were 2.0 and 4.0 microg/ml, respectively, while the MIC(50) and MIC(90) of
      azithromycin were 1.0 and 2.0 microg/ml, respectively. The MIC(50) and MIC(90) of
      erythromycin were 4.0 and 8.0 microg/ml, respectively; and those of
      clarithromycin were 4.0 and 16.0 microg/ml, respectively. All compounds except
      telithromycin were bactericidal (99.9% killing) against nine strains at two times
      the MIC after 24 h. Telithromycin was bactericidal against eight of the nine
      strains. In addition, both novel macrolides and telithromycin at two times the
      MIC showed 99% killing of all nine strains after 12 h and 90% killing of all
      strains after 6 h. After 24 h, all drugs were bactericidal against four to seven
      strains when they were tested at the MIC. Ten of 11 strains tested by multistep
      selection analysis yielded resistant clones after 14 to 43 passages with
      erythromycin. Azithromycin gave resistant clones of all strains after 20 to 50
      passages, and clarithromycin gave resistant clones of 9 of 11 strains after 14 to
      41 passages. By comparison, GW 708408 gave resistant clones of 9 of 11 strains
      after 14 to 44 passages, and GW 773546 gave resistant clones of 10 of 11 strains
      after 14 to 45 passages. Telithromycin gave resistant clones of 7 of 11 strains
      after 18 to 45 passages. Mutations mostly in the L22 and L4 ribosomal proteins
      and 23S rRNA were detected in resistant strains selected with all compounds, with
      alterations in the L22 protein predominating. Single-step resistance selection
      studies at the MIC yielded spontaneous resistant mutants at frequencies of 1.5 x
      10(-9) to 2.2 x 10(-6) with GW 773546, 1.5 x 10(-9) to 6.0 x 10(-4) with GW
      708408, and 7.1 x 10(-9) to 3.8 x 10(-4) with telithromycin, whereas the
      frequencies were 1.3 x 10(-9) to 6.0 x 10(-4) with erythromycin and azithromycin
      and 2.0 x 10(-9) to 2.0 x 10(-3) with clarithromycin. Alterations in the L22
      protein (which were predominant) and the L4 protein were present in mutants
      selected by the single-step selection process. The postantibiotic effects of GW
      773546, GW 708408, and telithromycin for seven H. influenzae strains were 6.6 h
      (range, 5.2 to 8.8 h), 4.7 h (range, 2.6 to 6.9 h), and 6.4 h (range, 3.8 to 9.7
      h), respectively. The results of in vitro studies obtained with both novel
      macrolides were similar to those obtained with telithromycin and better than
      those obtained with older macrolides.

PMID- 15504830
TI  - Chemical diversity of polyene macrolides produced by Streptomyces noursei ATCC
      11455 and recombinant strain ERD44 with genetically altered polyketide synthase
      NysC.
AB  - The gram-positive bacterium Streptomyces noursei ATCC 11455 produces a complex
      mixture of polyene macrolides generally termed nystatins. Although the structures
      for nystatins A(1) and A(3) have been reported, the identities of other
      components of the nystatin complex remain obscure. Analyses of the culture
      extract from the S. noursei wild type revealed the presence of several nystatin
      related compounds for which chemical structures could be suggested on the basis
      of their molecular weights, their UV spectra, and knowledge of the nystatin
      biosynthetic pathway. Nuclear magnetic resonance (NMR) studies with one of these
      polyene macrolides identified it as a nystatin analogue containing a mycarose
      moiety at C-35. A similar investigation was performed with the culture extract of
      the ERD44 mutant, which has a genetically altered polyketide synthase (PKS) NysC
      and which was previously shown to produce a heptaene nystatin analogue. The
      latter compound, tentatively named S44HP, and its derivative, which contains two
      deoxysugar moieties, were purified; and their structures were confirmed by NMR
      analysis. Nystatin analogues with an expanded macrolactone ring were also
      observed in the extract of the ERD44 mutant, suggesting that the altered PKS can
      "stutter" during the polyketide chain assembly. These data provide new insights
      into the biosynthesis of polyene macrolide antibiotics and the functionalities of
      PKSs and post-PKS modification enzymes.

PMID- 15504831
TI  - Emergence of multidrug-resistant Salmonella enterica serovar typhi in Korea.
AB  - A chloramphenicol-resistant strain of Salmonella enterica serovar Typhi was first
      noted in Korea in 1992, when a resistant isolate was detected in a returned
      traveler. Continued isolation of multidrug-resistant (MDR) strains thereafter in
      other settings prompted a retrospective analysis of laboratory records and
      phenotypic and genotypic analyses of 12 chloramphenicol-resistant isolates. Among
      these, one isolate was resistant only to chloramphenicol, and the other isolates
      were also resistant to ampicillin and co-trimoxazole. MDR was transferred by
      conjugation from 9 of the 11 isolates. PCR showed that all isolates had an
      incompatible group HI1 plasmid, and oriT was detected in 10 isolates, which
      included strains with an unsuccessful transfer of resistance. All of the
      ampicillin-resistant isolates had a beta-lactamase band of pI 5.4 and bla(TEM)
      alleles. A PCR amplicon from an isolate showed that the sequences were identical
      to those of bla(TEM-1), suggesting that all isolates had a TEM-1 beta-lactamase.
      All isolates had class 1 integrons: 10 isolates had integrons of ca. 1.2 kb with
      dhfr7 gene cassettes, and 1 isolate had an integron of ca. 2.3 kb with aacA4 and
      bla(OXA-1)-like gene cassettes. The pulsed-field gel electrophoresis patterns of
      7 of 11 MDR isolates were identical and indistinguishable from those reported for
      isolates in India and Indonesia. In conclusion, some of the MDR strains in Korea
      are related to those in other Asian countries. Susceptibility testing became
      necessary for selection of antimicrobial agents for the optimal treatment of
      patients with the emergence of MDR Salmonella serovar Typhi in Korea.

PMID- 15504832
TI  - Four variants of the Citrobacter freundii AmpC-Type cephalosporinases, including
      novel enzymes CMY-14 and CMY-15, in a Proteus mirabilis clone widespread in
      Poland.
AB  - Twenty-nine Proteus mirabilis isolates from 17 Polish hospitals were analyzed.
      The isolates were resistant to a variety of antimicrobials, and their patterns of
      resistance to beta-lactams resembled those of the constitutive class C
      cephalosporinase (AmpC) producers. Indeed, beta-lactamases with a pI of
      approximately 9.0 were found in all of the isolates, and they were subsequently
      identified as four AmpC-type cephalosporinases, CMY-4, -12, -14, and -15, of
      which the two last ones were novel enzyme variants. The enzymes were of
      Citrobacter freundii origin and were closely related to each other, with CMY-4
      likely being the evolutionary precursor of the remaining ones. The bla(CMY) genes
      were located exclusively in chromosomal DNA, within EcoRI restriction fragments
      of the same size of approximately 10 kb. In the CMY-12- and -15-producing
      isolates, an additional fragment of approximately 4.5 kb hybridized with the
      bla(CMY) probe as well, which could have arisen from a duplication event during
      the evolution of the genes. In all of the isolates, the ISEcp1 mobile element,
      which most probably is involved in mobilization of the C. freundii ampC gene, was
      placed at the same distance from the 5' ends of the bla(CMY) genes, and sequences
      located between them were identical in isolates carrying each of the four genes.
      These data suggested that a single chromosome-to-chromosome transfer of the ampC
      gene from C. freundii to P. mirabilis could have initiated the spread and
      evolution of the AmpC-producing P. mirabilis in Poland. The hypothesis seems to
      be confirmed by pulsed-field gel electrophoresis typing, which revealed several
      cases of close relatedness between the P. mirabilis isolates from distant centers
      and showed an overall similarity between the majority of the multiresistant
      isolates.

PMID- 15504833
TI  - Effects of amoxicillin subinhibitory concentrations on the cross-protection
      developed by pneumococcal antibodies in mouse sepsis caused by an amoxicillin
      resistant serotype 6B Streptococcus pneumoniae strain.
AB  - A model of mouse sepsis caused by a serotype 6B Streptococcus pneumoniae strain
      (amoxicillin MIC of 8 microg/ml) was developed to investigate the therapeutic
      effect of an amoxicillin dose (3.12 mg/kg of body weight three times daily for 48
      h) producing, over the whole treatment period, subinhibitory concentrations in
      serum (peak concentration [C(max)]: 6.1 microg/ml) in animals that prior to
      infection had been passively immunized with a 6B or 23F hyperimmune serum
      (obtained by immunization with a whole-cell heat-inactivated inoculum and diluted
      to produce no protective effect by itself). Mortality in nonimmunized animals
      treated with antibiotic (3.12 mg/kg) was 90%, and mortality in animals immunized
      but not treated with the antibiotic was 100%. Antibiotic treatment in immunized
      animals produced mortality rates </=20% when the hyperimmune serum was used, thus
      showing cross-protection and synergism (defined as the situation in which there
      is no response to the single agents [no differences versus placebo] while the
      combination exhibits significant activity) with subinhibitory concentrations of
      the antibiotic. The presence of antipneumococcal antibodies allowed antibiotic
      efficacy with negligible values of pharmacodynamic parameters (C(max)/MIC ratio
      of <1 and thus a null value for the time that serum levels exceed the MIC). This
      in vivo synergism offers a potential therapeutic strategy against resistant
      strains.

PMID- 15504834
TI  - Nevirapine significantly reduces the levels of racemic methadone and (R)
      methadone in human immunodeficiency virus-infected patients.
AB  - Methadone is metabolized by various isoforms of the cytochrome P450 family, which
      can be induced by many drugs, including nevirapine. The objective of the present
      study was to determine the effects of coadministration of nevirapine and
      methadone on the dose-adjusted areas under the concentration-time curves (AUCs)
      of racemic and (R)-methadone. Twenty-five human immunodeficiency virus-infected
      subjects taking stable single daily doses of racemic methadone or (R)-methadone
      were included in this prospective, single-crossover trial. At the baseline,
      nevirapine was either started as part of a new regimen containing two nucleoside
      reverse transcriptase inhibitors (NRTIs) or added to an ongoing NRTI regimen.
      Patients could increase their methadone doses if withdrawal symptoms developed.
      Twelve-hour pharmacokinetic profiles were obtained before and 28 days after the
      start of nevirapine treatment. The total concentrations of methadone and its
      inactive metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), in
      serum were determined by liquid chromatography-tandem mass spectrometry. Among
      the 20 evaluable patients, coadministration of nevirapine significantly decreased
      the mean dose-adjusted AUC of methadone by 41%. AUC reductions were similar for
      patients taking racemic methadone (37%; n = 11) and (R)-methadone (44%; n = 9).
      AUC changes ranged from mild increases in three patients to decreases of up to
      70%. Fourteen of 20 patients required additional methadone due to withdrawal
      symptoms. However, the median dose increase was only 15%, which was less than
      that which would have been expected from the pharmacokinetic data. The AUC of
      EDDP increased significantly, by 35%. Methadone dose adjustments are justified
      when methadone is coadministered with nevirapine. Due to extensive variability,
      the adjustments must be tailored to the individual patient's needs.

PMID- 15504835
TI  - Novel chemical class of pUL97 protein kinase-specific inhibitors with strong
      anticytomegaloviral activity.
AB  - Human cytomegalovirus (HCMV) is a major human pathogen frequently associated with
      life-threatening disease in immunosuppressed patients and newborns. The HCMV UL97
      encoded protein kinase (pUL97) represents an important determinant of viral
      replication. Recent studies demonstrated that pUL97-specific kinase inhibitors
      are powerful tools for the control of HCMV replication. We present evidence that
      three related quinazoline compounds are potent inhibitors of the pUL97 kinase
      activity and block in vitro substrate phosphorylation, with 50% inhibitory
      concentrations (IC(50)s) between 30 and 170 nM. Replication of HCMV in primary
      human fibroblasts was suppressed with a high efficiency. The IC(50)s of these
      three quinazoline compounds (2.4 +/- 0.4, 3.4 +/- 0.6, and 3.9 +/- 1.1 microM,
      respectively) were in the range of the IC(50) of ganciclovir (1.2 +/- 0.2
      microM), as determined by the HCMV green fluorescent protein-based antiviral
      assay. Importantly, the quinazolines were demonstrated to have strong inhibitory
      effects against clinical HCMV isolates, including ganciclovir- and cidofovir
      resistant virus variants. Moreover, in contrast to ganciclovir, the formation of
      resistance to the quinazolines was not observed. The mechanisms of action of
      these compounds were confirmed by kinetic analyses with infected cells.
      Quinazolines specifically inhibited viral early-late protein synthesis but had no
      effects at other stages of the replication cycle, such as viral entry, consistent
      with a blockage of the pUL97 function. In contrast to epithelial growth factor
      receptor inhibitors, quinazolines affected HCMV replication even when they were
      added hours after virus adsorption. Thus, our findings indicate that quinazolines
      are highly efficient inhibitors of HCMV replication in vitro by targeting pUL97
      protein kinase activity.

PMID- 15504836
TI  - Multidrug resistance of a porin deletion mutant of Mycobacterium smegmatis.
AB  - Mycobacteria contain an outer membrane of unusually low permeability which
      contributes to their intrinsic resistance to many agents. It is assumed that
      small and hydrophilic antibiotics cross the outer membrane via porins, whereas
      hydrophobic antibiotics may diffuse through the membrane directly. A mutant of
      Mycobacterium smegmatis lacking the major porin MspA was used to examine the role
      of the porin pathway in antibiotic sensitivity. Deletion of the mspA gene caused
      high-level resistance of M. smegmatis to 256 microg of ampicillin/ml by
      increasing the MIC 16-fold. The permeation of cephaloridine in the mspA mutant
      was reduced ninefold, and the resistance increased eightfold. This established a
      clear relationship between the activity and the outer membrane permeation of
      cephaloridine. Surprisingly, the MICs of the large and/or hydrophobic antibiotics
      vancomycin, erythromycin, and rifampin for the mspA mutant were increased 2- to
      10-fold. This is in contrast to those for Escherichia coli, whose sensitivity to
      these agents was not affected by deletion of porin genes. Uptake of the very
      hydrophobic steroid chenodeoxycholate by the mspA mutant was retarded threefold,
      which supports the hypothesis that loss of MspA indirectly reduces the
      permeability by the lipid pathway. The multidrug resistance of the mspA mutant
      highlights the prominent role of outer membrane permeability for the sensitivity
      of M. smegmatis to antibiotics. An understanding of the pathways across the outer
      membrane is essential to the successful design of chemotherapeutic agents with
      activities against mycobacteria.

PMID- 15504837
TI  - Inhibition of antibiotic efflux in bacteria by the novel multidrug resistance
      inhibitors biricodar (VX-710) and timcodar (VX-853).
AB  - Inhibitors of mammalian multidrug efflux, such as the plant alkaloid reserpine,
      are also active in potentiating antibiotic activity by inhibiting bacterial
      efflux. Based on this precedent, two novel mammalian multiple drug resistance
      inhibitors, biricodar (VX-710) and timcodar (VX-853), were evaluated for activity
      in a variety of bacteria. Both VX-710 and VX-853 potentiated the activity of
      ethidium bromide (EtBr), a model efflux substrate, against three clinically
      significant gram-positive pathogens: Staphylococcus aureus, Enterococcus
      faecalis, and Streptococcus pneumoniae. Similar to reserpine, VX-710 and VX-853
      directly blocked EtBr efflux in S. aureus. Furthermore, these compounds were
      effective in lowering the MICs of several clinically used antibiotics, including
      fluoroquinolones, suggesting that VX-710 and VX-853 are representatives of a new
      class of bacterial efflux inhibitors with the potential for use in combination
      therapy.

PMID- 15504838
TI  - Promoter sequences necessary for high-level expression of the plasmid-associated
      ampC beta-lactamase gene blaMIR-1.
AB  - Little is known about mechanisms involved in high-level expression of plasmid
      associated ampC genes. The sequence for bla(MIR-1) has been elucidated, and the
      gene is not inducible. Although the sequence for the promoter (prA) that drives
      expression of Enterobacter cloacae chromosomal ampC is present upstream of
      bla(MIR-1), high-level expression from bla(MIR-1) is directed from a hybrid
      promoter (prB) located further upstream of prA. The purpose of this study was to
      determine the influence of each promoter on bla(MIR-1) expression and beta-lactam
      resistance. RNA expression by deletion clones with both promoters was measured
      and compared to that by clones in which -35 and/or -10 elements of prA and/or prB
      were altered. Primer extension revealed two start sites for bla(MIR-1)
      transcription. Expression of bla(MIR-1) in clones with both promoters was 171
      fold higher than that in clones carrying only prA. In addition, bla(MIR-1)
      expression from prA increased 11-fold in the presence of the prB -10 element
      compared to expression driven from prA alone. Ceftazidime and cefotaxime MICs
      increased 42- and 64-fold, respectively, for the clone expressing bla(MIR-1) from
      both promoters compared to expression from prA alone. The upstream promoter prB
      of bla(MIR-1) is solely responsible for high-level expression required for
      cefotaxime and ceftazidime resistance. These data suggest that resistance to
      extended-spectrum cephalosporins mediated by noninducible plasmid-associated ampC
      genes requires the formation of novel promoter elements that are capable of
      increasing ampC expression.

PMID- 15504839
TI  - Emergence and persistence of macrolide resistance in oropharyngeal flora and
      elimination of nasal carriage of Staphylococcus aureus after therapy with slow
      release clarithromycin: a randomized, double-blind, placebo-controlled study.
AB  - To investigate the effect of slow-release (SR) clarithromycin on colonization and
      the development of resistance in oropharyngeal and nasal flora, a double-blind,
      randomized, placebo-controlled trial was performed with 8 weeks of follow-up. A
      total of 296 patients with documented coronary artery disease were randomized in
      the preoperative outpatient clinic to receive a daily dose of SR clarithromycin
      (500 mg) (CL group) or placebo tablets (PB group) until the day of surgery. Nose
      and throat swabs were taken before the start of therapy, directly after the end
      of therapy, and 8 weeks later. The presence of potential pathogenic bacteria was
      determined, and if they were isolated, MIC testing was performed. Quantitative
      culture on media with and without macrolides was performed for the indigenous
      oropharyngeal flora. In addition, analysis of the mechanism of resistance was
      performed with the macrolide-resistant indigenous flora. Basic patient
      characteristics were comparable in the two treatment groups. The average number
      of tablets taken was 15 (standard deviation = 6.4). From the throat swabs,
      Haemophilus parainfluenzae was isolated and carriage was not affected in either
      of the treatment groups. Nasal carriage of Staphylococcus aureus, however, was
      significantly reduced in the CL group (from 35.3 to 4.3%) compared to the PB
      group (from 32.4 to 30.3%) (P < 0.0001; relative risk [RR], 7.0; 95% confidence
      interval [CI], 3.1 to 16.0). Resistance to clarithromycin was present
      significantly more frequently in H. parainfluenzae in the CL group after
      treatment (P = 0.007; RR, 1.6; 95% CI, 1.1 to 2.3); also, the percentage of
      patients with resistance to macrolides in the indigenous flora after treatment
      was significantly higher in the CL group (31 to 69%) (P < 0.0001; RR, 1.9; 95%
      CI, 1.4 to 2.5). This persisted for at least 8 weeks. This study shows that
      besides the effective elimination of nasal carriage of S. aureus, treatment with
      SR clarithromycin for approximately 2 weeks has a marked and sustained effect on
      the development of resistance in the oropharyngeal flora for at least 8 weeks.

PMID- 15504840
TI  - Differential maintenance of the M184V substitution in the reverse transcriptase
      of human immunodeficiency virus type 1 by various nucleoside antiretroviral
      agents in tissue culture.
AB  - The M184V substitution in human immunodeficiency virus type 1 reverse
      transcriptase (RT) is rapidly selected in tissue culture following serial passage
      of wild-type virus in the presence of increasing concentrations of lamivudine
      (3TC). M184V is also associated with several alterations of RT enzymatic function
      in vitro that may adversely affect viral fitness or replication capacity, which
      creates a potential rationale for its maintenance once it has been selected by
      antiviral chemotherapy. However, the relative effectiveness of nucleoside RT
      inhibitors that are structurally unrelated to 3TC in selecting and/or maintaining
      M184V has not been investigated. In the present study, we have studied the
      abilities of a variety of drugs, i.e., zalcitabine (ddC), didanosine (ddI),
      abacavir (ABC), and the novel nucleoside SPD754, in addition to 3TC, to maintain
      the presence of M184V in tissue culture and have shown that SPD754, ABC, and 3TC
      are able to preserve M184V in mixed dual infections consisting of wild-type
      viruses and clinical isolates which contained the M184V mutation. Moreover, M184V
      could also be maintained in these cultures when a subtherapeutic concentration of
      3TC (i.e., 0.05 microM) was used. In contrast, neither ddI nor ddC was able to
      maintain M184V to the same extent as the other drugs after 10 weeks of tissue
      culture in mixtures of wild-type viruses and isolates containing M184V in
      different proportions.

PMID- 15504841
TI  - Pharmacodynamics of pulse dosing versus standard dosing: in vitro metronidazole
      activity against Bacteroides fragilis and Bacteroides thetaiotaomicron.
AB  - Pulse dosing is a novel approach to dosing that produces escalating antibiotic
      levels early in the dosing interval followed by a prolonged dose-free period.
      Antibiotic is frontloaded by means of four sequential bolus injections, after
      which antibiotic levels are allowed to diminish until the next dose. This study
      compares standard thrice-daily dosing and pulse dosing of metronidazole against
      Bacteroides spp. in an in vitro model. Two American Type Culture Collection
      Bacteroides fragilis isolates (metronidazole MIC for each organism = 1 mg/liter)
      were exposed to metronidazole for 48 or 96 h. Human pharmacokinetics were
      simulated for an oral 500-mg dose given every 8 h (maximum concentration of drug
      [C(max)] = 12 mg/liter; half-life = 8 h; area under the curve [AUC] = 294 mg .
      h/liter) and for pulse dosing. Pulses, each producing an increase in
      metronidazole concentration of 9 mg/liter, were administered at times 0, 2, 4,
      and 6 h of each 24-h cycle, with a targeted half-life of 8 h (AUC = 347 mg .
      h/liter). A metronidazole-resistant B. fragilis strain (metronidazole MIC = 32
      mg/liter) was exposed to both dosing regimens and, additionally, to a regimen of
      1,500 mg administered once daily (C(max) = 36 mg/liter; AUC = 364 mg . h/liter).
      Furthermore, regimens against one B. fragilis isolate and one B. thetaiotaomicron
      isolate corresponding to one-fourth and one-eighth of the thrice-daily and pulse
      dosing regimens, mimicking peak metronidazole concentrations achieved in
      abscesses, were simulated in 48-h experiments (metronidazole MIC = 1 mg/liter).
      Time-kill curves were generated for each experiment and analyzed for bactericidal
      activity, defined as a bacterial burden reduction >/= 3 log(10) CFU/ml. The
      results of paired (Wilcoxon matched-pair signed-rank test) and nonpaired (Mann
      Whitney test) statistical analyses conducted on time to 3 log(10) kill data and
      area under the kill curve data from each of the thrice-daily dosing experiments
      versus each of the pulse dosing experiments were considered not significant for a
      given isolate-dosing regimen combination. The thrice-daily dosing, pulse dosing,
      and once-daily dosing regimens all exhibited bactericidal activity. Metronidazole
      administered in standard or pulse dosing fashion was highly active against both
      susceptible and resistant strains of Bacteroides spp.

PMID- 15504842
TI  - Pharmacokinetics of indinavir and ritonavir administered at 667 and 100
      milligrams, respectively, every 12 hours compared with indinavir administered at
      800 milligrams every 8 hours in human immunodeficiency virus-infected patients.
AB  - Human immunodeficiency virus (HIV) patients on nucleoside or nucleotide reverse
      transcriptase inhibitors with HIV RNA at <1,000 copies/ml were randomized in an
      open-label study to administration of combined indinavir/ritonavir (IDV/RTV) at
      667/100 mg every 12 h (q12h) or IDV alone at 800 mg q8h to determine the
      regimens' pharmacokinetics. On day 14, plasma IDV and RTV levels were determined
      over 24 h. Noncompartmental pharmacokinetics (minimum concentration of drug in
      serum [C(min)], area under the concentration-time curve from 0 to 24 h [AUC(0
      24)], and maximum concentration of drug in serum [C(max)]) were expressed as
      geometric mean values with 90% confidence intervals (CI). The primary hypothesis
      was that the lower bound of the protocol-specified 90% CI for the geometric mean
      C(min) ratio of the combination compared to IDV alone regimen would be >/=2.
      Twenty-seven patients were enrolled, and 24 (15 male; average age, 42 years)
      completed the study. The C(min), AUC(0-24), and C(max) for IDV/RTV compared to
      IDV alone were 1,511 versus 250 nM, 119,557 versus 77,034 nM . h, and 10,428
      versus 10,407 nM, respectively. Corresponding relationships for IDV/RTV compared
      to IDV alone were a 6.0-fold increase in C(min) (90% CI, 4.0, 9.3), an increase
      in AUC(0-24) (1.5-fold, 90% CI, 1.2, 2.0), and no increase in C(max). Adverse
      events were similar and generally mild, with no cases of nephrolithiasis. The
      geometric mean ratio of IDV C(min) for IDV/RTV compared to IDV was at least 2 by
      a lower bound of the 90% CI, satisfying the primary hypothesis. The C(max) was
      not increased, suggesting an IDV/RTV 667/100-mg toxicity profile may be similar
      to that of unboosted IDV.

PMID- 15504843
TI  - Highly active anti-Pneumocystis carinii compounds in a library of novel
      piperazine-linked bisbenzamidines and related compounds.
AB  - Trimethoprim-sulfamethoxazole and pentamidine isethionate have been used
      extensively for the prophylaxis and therapy of pneumonia caused by Pneumocystis
      jirovecii. Problems associated with toxicity and potential emerging resistance
      for both therapies necessitate the development of safe and effective analogs or
      new treatment strategies. In the present study, a library of 36 compounds was
      synthesized by using the pentamidine molecule as the parent compound modified by
      a 1,4-piperazinediyl moiety as the central linker to restrict conformation
      flexibility. The compounds were evaluated for anti-Pneumocystis carinii activity
      in a bioluminescent ATP-driven assay. Four of the compounds were highly active,
      with 50% inhibitory concentration (IC(50)) values of <0.01 microg/ml; four had
      very marked activity (IC(50) < 0.10 microg/ml); ten had marked activity (IC(50) <
      1.0 microg/ml); nine had moderate activity (IC(50) < 10 microg/ml); one had
      slight activity (IC(50) = 34.1 microg/ml); and the remaining eight did not
      demonstrate activity in this assay system. The high level of activity was
      specifically associated with an alkyl chain length of five to six carbons
      attached to one of the nitrogens of the bisamidinium groups. None of the highly
      active compounds and only one of the very marked compounds exhibited any toxicity
      when evaluated in three mammalian cell lines. The strategy of substitution of 1,4
      piperazine-linked bisbenzamidines produced compounds with the highest level of
      activity observed in the ATP assay and holds great promise for the development of
      efficacious anti-P. carinii therapy.

PMID- 15504844
TI  - OXA-60, a chromosomal, inducible, and imipenem-hydrolyzing class D beta-lactamase
      from Ralstonia pickettii.
AB  - A chromosomally encoded oxacillinase, OXA-22, had been characterized from
      Ralstonia pickettii PIC-1 that did not explain by itself the resistance profile
      of this strain to beta-lactams. Thus, further analysis of the genetic background
      of this species led to the identification of another oxacillinase, OXA-60, that
      was expressed only after beta-lactam induction. This chromosomally encoded
      oxacillinase shared 19% amino acid identity with OXA-22. It has a narrow-spectrum
      hydrolysis profile that includes imipenem. OXA-60-like enzymes were identified in
      several R. pickettii strains. Gene inactivation and induction studies of the
      bla(OXA-60) and bla(OXA-22) genes in R. pickettii identified the relative
      contribution of each oxacillinase to the resistance profile of R. pickettii to
      beta-lactams.

PMID- 15504845
TI  - Hypermutation and the preexistence of antibiotic-resistant Pseudomonas aeruginosa
      mutants: implications for susceptibility testing and treatment of chronic
      infections.
AB  - Whether or not resistant mutants will be present before the start of antibiotic
      treatment of an initially susceptible population of bacteria depends on the size
      of the infecting population, the rate of mutation to resistance, and the amount
      of time that the population has been maintained. In the present investigation, we
      argue that for the treatment of chronic infections caused by hypermutable
      Pseudomonas aeruginosa of the sort frequently found in cystic fibrosis patients,
      mutants resistant to all single antipseudomonal drugs will almost invariably be
      present in a high proportion at the onset of treatment, and consequently, these
      strains should be considered resistant to all agents when they are used as
      monotherapy. Using a construct of P. aeruginosa strain PAO1 with a mutS deletion
      (strain PAODeltamutS), we show that when in vitro populations of less than 5 x
      10(4) seemingly susceptible hypermutable bacteria are confronted with any of 11
      antipseudomonal agents, mutants for which the MICs and the minimum bactericidal
      concentrations are in the range of clinical resistance will almost invariably
      ascend to dominance within 24 to 36 h. This does not occur for PAO1 without the
      mutS deletion. The results of our detailed analysis of this evolution of acquired
      resistance to two of these antibiotics, imipenem and ciprofloxacin, indicate that
      although the rates of mutation to resistance in PAODeltamutS are on the order of
      1 x 10(-6) per generation, resistant mutants are very likely to either be present
      in cultures of between 2 x 10(4) and 4 x 10(4) bacteria or arise after the
      bacterial populations are confronted with antibiotics. We also demonstrate with
      in vitro experiments that the problem of acquired resistance to treatment with
      single antibiotics can be thwarted by combination therapy with pairs of
      antibiotics of different classes with synergistic activities. We discuss the
      clinical implications of our analysis of these observations.

PMID- 15504846
TI  - Comparative pharmacokinetics of intramuscular artesunate and artemether in
      patients with severe falciparum malaria.
AB  - The first-dose pharmacokinetic properties of intramuscular (i.m.) artesunate
      (ARTS; 2.4 mg/kg immediately [stat], followed by 1.2 mg/kg i.m. daily) and
      artemether (ARM; 3.2 mg/kg i.m. stat, followed by 1.6 mg/kg i.m. daily) were
      compared in Vietnamese adults with severe falciparum malaria. A total of 19
      patients were studied; 9 received ARTS, and 10 received ARM. ARTS was absorbed
      very rapidly; concentrations in plasma peaked between 1,362 and 8,388 nmol/liter
      (median, 5,710 nmol/liter) within 20 min of injection and then declined with a
      median (range) half-life (t(1/2)) of 30 (3 to 67) min. ARTS was hydrolyzed
      rapidly and completely to the biologically active metabolite dihydroartemisinin
      (DHA). Peak DHA concentrations in plasma ranged between 1,718 and 7,080
      nmol/liter (median, 3,060 nmol/liter) and declined with a t(1/2) of 52 (26 to 69)
      min. In contrast, ARM was slowly and erratically absorbed. The absorption profile
      appeared biphasic. Maximum ARM concentrations in plasma ranged between 67
      nmol/liter (a value close to the 50% inhibitory concentration for some Plasmodium
      falciparum isolates) and 1,631 nmol/liter (median, 574 nmol/liter) and occurred
      at a median (range) of 10 (1.5 to 24) h. There was relatively little conversion
      to DHA. After i.m. injection in cases of severe malaria, absorption of the water
      soluble ARTS is rapid and extensive, whereas the oil-based ARM is slowly and
      erratically absorbed, with relatively little conversion to the more active DHA.
      On the basis of this pharmacological study, parenteral ARTS is preferable to ARM
      as an initial antimalarial therapy, particularly in the most seriously ill
      patients. These findings should be formally assessed by a randomized clinical
      trial.

PMID- 15504847
TI  - Evolution of the antimicrobial resistance of Staphylococcus spp. in Spain: five
      nationwide prevalence studies, 1986 to 2002.
AB  - Data regarding the evolution of Staphylococcus resistance in a whole country have
      a definite influence on the design of empirical treatment regimens. Nevertheless,
      incidence studies over long periods of time are expensive and very difficult to
      carry out. In order to ascertain the present situation of the antimicrobial
      resistance of Staphylococcus in Spain and the change of this resistance over
      time, we performed five point prevalence studies (1986 to 2002) in a large group
      of Spanish hospitals (from 68 institutions in 1986 to 143 in 2002) collecting all
      Staphylococcus strains isolated on a single selected day. All microorganisms were
      identified in the five studies at the same laboratory, and antimicrobial
      susceptibility testing was performed against 17 antimicrobial agents by the agar
      dilution method and a microdilution method. During this period, there was an
      overall increase in resistance to most antimicrobials among Staphylococcus
      aureus/coagulase-negative staphylococci, mainly to oxacillin (1.5%/32.5% in 1986
      versus 31.2%/61.3% in 2002) (P < 0.001), erythromycin (7%/41.1% in 1986 versus
      31.7%/63% in 2002) (P < 0.001), gentamicin (5.2%/25.4% in 1986 versus 16.9%/27.8%
      in 2002) (P < 0.001; P = 0.5), and ciprofloxacin (0.6%/1.1% in 1986 versus
      33.9%/44.9% in 2002) (P < 0.001). All of the isolates were uniformly susceptible
      to glycopeptides, linezolid, and quinupristin/dalfopristin. Resistance of S.
      aureus to trimethoprim/sulfamethoxazole was very low (from 0.5% to 2.1%) (P =
      0.152). Periodic performance of prevalence studies is a useful, inexpensive, and
      easy tool to know the nationwide situation of a microorganism and its resistance
      to antimicrobials; it also helps us assess the emergence and spread of
      antimicrobial resistance.

PMID- 15504848
TI  - Concentrations of gemifloxacin at the target site in healthy volunteers after a
      single oral dose.
AB  - Free gemifloxacin concentrations in the interstitial space fluid of skeletal
      muscle and subcutaneous adipose tissue were measured by means of in vivo
      microdialysis to characterize the ability of gemifloxacin to penetrate human soft
      tissues. Twelve healthy volunteers received a single oral dose of 320 mg of
      gemifloxacin. The mean areas under the concentration-time curves from 0 to 10 h
      (AUC(0-10)) were significantly higher for soft tissue than for unbound
      gemifloxacin in plasma (P < 0.05). The ratios of the mean AUC(0-10) for tissue to
      the AUC(0-10) for free gemifloxacin in plasma were 1.7 +/- 0.7 (mean +/- standard
      deviation) for skeletal muscle and 2.4 +/- 1.0 for adipose tissue. The AUC(0-24)
      ratios for free gemifloxacin in tissues to the MIC at which 90% of frequently
      isolated bacteria are inhibited were close to or higher than 100 h. Therefore,
      based on pharmacokinetic and pharmacodynamic calculations, we conclude that
      gemifloxacin might be a useful therapeutic option for the treatment of soft
      tissue infections.

PMID- 15504849
TI  - Complex multiple antibiotic and mercury resistance region derived from the r-det
      of NR1 (R100).
AB  - The sequence of the 45.2-kb multidrug and mercury resistance region of pRMH760, a
      large plasmid from a clinical isolate of Klebsiella pneumoniae collected in 1997
      in Australia, was completed. Most of the modules found in the resistance
      determinant (r-det), or Tn2670, region of NR1 (also known as R100), isolated from
      a Shigella flexneri strain in Japan in the late 1950s, were present in pRMH760
      but in a different configuration. The location was also different, with the
      Tn2670-derived region flanked by the transposition module of Tn1696 and a mercury
      resistance module almost identical to one found in the plasmid pDU1358. This
      arrangement is consistent with a three-step process. First, the r-det was
      circularized via homologous recombination between the IS1 elements and
      reincorporated at a new location, possibly in a different plasmid, via homologous
      recombination between the 5'-conserved (5'-CS) or 3'-CS of the In34 integron in
      the r-det and the same region of a second class 1 integron in a Tn1696 relative.
      Subsequently, resolvase-mediated recombination between the res sites in the r-det
      and a second mercury resistance transposon removed one end of the Tn1696-like
      transposon and part of the second transposon. Other events occurring within the r
      det-derived portion have also contributed to the formation of the pRMH760
      resistance region. Tn2 or a close relative that includes the bla(TEM-1b) gene had
      moved into the Tn21 mercury resistance module with subsequent deletion of the
      adjacent sequence, and all four 38-bp inverted repeats corresponding to Tn21
      family transposon termini have been interrupted by an IS4321-like element.

PMID- 15504850
TI  - Steady-state pharmacokinetics of a double-boosting regimen of saquinavir soft gel
      plus lopinavir plus minidose ritonavir in human immunodeficiency virus-infected
      adults.
AB  - Management of treatment-experienced human immunodeficiency virus patients has
      become complex, and therapy may need to include two protease inhibitors at
      therapeutic doses. The objective of this study was to characterize the
      pharmacokinetics in serum of saquinavir (1,000 mg twice daily [b.i.d.]),
      lopinavir (400 mg b.i.d.), and ritonavir (100 mg b.i.d.) in a multidrug rescue
      therapy study and to investigate whether steady-state pharmacokinetics of
      lopinavir-ritonavir are affected by coadministration of saquinavir. Forty
      patients were included (25 given ritonavir, lopinavir, and saquinavir and 15
      given ritonavir and lopinavir). The median pharmacokinetic parameters of
      lopinavir were as follows: area under the concentration-time curve from 0 to 12 h
      (AUC(0-12)), 85.1 microg/ml . h; maximum concentration of drug in serum (C(max)),
      10.0 microg/ml; trough concentration of drug in serum (C(trough)), 7.3 microg/ml;
      and minimum concentration of drug in serum (C(min)), 5.5 microg/ml. Lopinavir
      concentrations were similar in patients with and without saquinavir. The median
      pharmacokinetic parameters for saquinavir were as follows: AUC(0-12), 22.9
      microg/ml . h; C(max), 2.9 microg/ml; C(trough), 1.6 microg/ml; and C(min), 1.4
      microg/ml. There was a strong linear correlation between lopinavir and ritonavir
      and between saquinavir and ritonavir concentrations in plasma. The correlation
      between lopinavir and saquinavir levels was weaker. We found higher saquinavir
      concentrations in women than in men, with no difference in lopinavir levels. Only
      patients with very high body weight presented lopinavir and saquinavir
      concentrations lower than the overall group. Ritonavir has a double-boosting
      function for both lopinavir and saquinavir, and in terms of pharmacokinetics, the
      drug doses selected seemed appropriate for combining these agents in a dual
      protease inhibitor-based antiretroviral regimen for patients with several prior
      virologic failures.

PMID- 15504851
TI  - Infections with nontyphoidal Salmonella species producing TEM-63 or a novel TEM
      enzyme, TEM-131, in South Africa.
AB  - Salmonella spp. producing extended-spectrum beta-lactamases (ESBLs) have been
      reported in many countries, but there is no information on their prevalence in
      Africa. ESBL-producing Salmonella enterica serotype Isangi and S. enterica
      serotype Typhimurium strains have been noted in South Africa since 2001. A total
      of 160 consecutive isolates of Salmonella spp. were collected from 13 hospitals
      located in different cities in South Africa over a 5-month period from December
      2002 to April 2003. All strains were screened for production of ESBLs by the
      double disk diffusion test and for AmpC production by assessing resistance to
      cefoxitin. bla(SHV), bla(TEM), bla(CTX-M), and bla(CMY-2) were sought from all
      ESBL-positive and cefoxitin-resistant isolates. A total of 15.6% (25 of 160)
      isolates produced SHV or TEM ESBLs, and 1.9% (3 of 160) produced CMY-2. Nine S.
      enterica serotype Typhimurium, eight S. enterica serotype Isangi, and three S.
      enterica serotype Muenchen strains produced either TEM-63 or a derivative of TEM
      63 designated TEM-131. Both TEM-63 and TEM-131 have an isoelectric point of 5.6,
      and their sequences have the following amino acid substitutions compared to the
      TEM-1 sequence: Leu21Phe, Glu104Lys, Arg164Ser, and Met182Thr. Additionally, TEM
      131 has an Ala237Thr substitution. ESBL-producing Salmonella spp. have become a
      significant public health problem in South Africa with particular implications
      for the treatment of serious nontyphoidal Salmonella infections in children, for
      whom extended-spectrum cephalosporins were the preferred treatment.

PMID- 15504852
TI  - In vivo assessment of drug efficacy against Plasmodium falciparum malaria:
      duration of follow-up.
AB  - To determine the optimum duration of follow-up for the assessment of drug
      efficacy against Plasmodium falciparum malaria, 96 trial arms from randomized
      controlled trials (RCTs) with follow-up of 28 days or longer that were conducted
      between 1990 and 2003 were analyzed. These trials enrolled 13,772 patients, and
      participating patients comprised 23% of all patients enrolled in RCTs over the
      past 40 years; 61 (64%) trial arms were conducted in areas where the rate of
      malaria transmission was low, and 58 (50%) trial arms were supported by parasite
      genotyping to distinguish true recrudescences from reinfections. The median
      overall failure rate reported was 10% (range, 0 to 47%). The widely used day 14
      assessment had a sensitivity of between 0 and 37% in identifying treatment
      failures and had no predictive value. Assessment at day 28 had a sensitivity of
      66% overall (28 to 100% in individual trials) but could be used to predict the
      true failure rate if either parasite genotyping was performed (r(2) = 0.94) or if
      the entomological inoculation rate was known. In the assessment of drug efficacy
      against falciparum malaria, 28 days should be the minimum period of follow-up.

PMID- 15504853
TI  - Heterologous expression of the enterococcal vanA operon in methicillin-resistant
      Staphylococcus aureus.
AB  - Two methicillin- and vancomycin-resistant Staphylococcus aureus strains, MI-VRSA
      and PA-VRSA, and Enterococcus faecalis DMC83006B, considered to be the potential
      donor of glycopeptide resistance to MI-VRSA, were studied. MI-VRSA is highly
      resistant to both glycopeptides, whereas PA-VRSA displays low-level resistance to
      vancomycin and reduced susceptibility to teicoplanin. We have analyzed the
      expression of the vanA operon in the three clinical isolates. Determination of
      the relative amounts of late peptidoglycan precursors and quantification of the
      d,d-peptidase activities, in the absence or after induction by glycopeptides,
      revealed that the resistance genes were expressed at similarly high levels in the
      three strains. Glycopeptide resistance stability in the three strains was studied
      by replica plating. Resistance was lost at high frequency, ca. 50%, after
      overnight growth of PA-VRSA in the absence of antibiotics, whereas it was fully
      stable in MI-VRSA and E. faecalis DMC83006B. Induction of resistance by
      vancomycin was significantly delayed in PA-VRSA relative to MI-VRSA. Low-level
      glycopeptide resistance of S. aureus PA-VRSA is thus likely due to instability of
      the genetic element, plasmid or transposon, carrying the vanA operon associated
      with a longer lag phase before growth resumes after induction by vancomycin.

PMID- 15504854
TI  - Activity of the new triazole derivative albaconazole against Trypanosoma
      (Schizotrypanum) cruzi in dog hosts.
AB  - Albaconazole is an experimental triazole derivative with potent and broad
      spectrum antifungal activity and a remarkably long half-life in dogs, monkeys,
      and humans. In the present work, we investigated the in vivo activity of this
      compound against two strains of the protozoan parasite Trypanosoma
      (Schizotrypanum) cruzi, the causative agent of Chagas' disease, using dogs as
      hosts. The T. cruzi strains used in the study were previously characterized
      (murine model) as susceptible (strain Berenice-78) and partially resistant
      (strain Y) to the drugs currently in clinical use, nifurtimox and benznidazole.
      Our results demonstrated that albaconazole is very effective in suppressing the
      proliferation of the parasite and preventing the death of infected animals.
      Furthermore, the parasitological, PCR, serological, and proliferative assay
      results indicated parasitological cure indices of 25 and 100% among animals
      inoculated with T. cruzi strain Y when they were treated with albaconazole at 1.5
      mg/kg of body weight/day for 60 and 90 days, respectively. On the other hand,
      although albaconazole given at 1.5 mg/kg/day was very effective in suppressing
      the proliferation of the parasite in animals infected with the Berenice-78 T.
      cruzi strain, no parasitological cure was observed among them, even when a longer
      treatment period (150 doses) was used. In conclusion, our results demonstrate
      that albaconazole has trypanocidal activity in vivo and is capable of inducing
      radical parasitological cure, although natural resistance to this compound was
      also indicated. Furthermore, the compound can be used in long-term treatment
      schemes (60 to 150 days) with minimal toxicity and thus represents a potentially
      useful candidate for the treatment of human Chagas' disease.

PMID- 15504855
TI  - Rapid direct detection of multiple rifampin and isoniazid resistance mutations in
      Mycobacterium tuberculosis in respiratory samples by real-time PCR.
AB  - Rapid detection of resistance in Mycobacterium tuberculosis can optimize the
      efficacy of antituberculous therapy and control the transmission of resistant M.
      tuberculosis strains. Real-time PCR has minimized the time required to obtain the
      susceptibility pattern of M. tuberculosis strains, but little effort has been
      made to adapt this rapid technique to the direct detection of resistance from
      clinical samples. In this study, we adapted and evaluated a real-time PCR design
      for direct detection of resistance mutations in clinical respiratory samples. The
      real-time PCR was evaluated with (i) 11 clinical respiratory samples harboring
      bacilli resistant to isoniazid (INH) and/or rifampin (RIF), (ii) 10 culture
      negative sputa spiked with a set of strains encoding 14 different resistance
      mutations in 10 independent codons, and (iii) 16 sputa harboring susceptible
      strains. The results obtained with this real-time PCR design completely agreed
      with DNA sequencing data. In all sputa harboring resistant M. tuberculosis
      strains, the mutation encoding resistance was successfully detected. No mutation
      was detected in any of the susceptible sputa. The test was applied only to smear
      positive specimens and succeeded in detecting a bacterial load equivalent to
      10(3) CFU/ml in sputum samples (10 acid-fast bacilli/line). The analytical
      specificity of this method was proved with a set of 14 different non-M.
      tuberculosis bacteria. This real-time PCR design is an adequate method for the
      specific and rapid detection of RIF and INH resistance in smear-positive clinical
      respiratory samples.

PMID- 15504856
TI  - Mutations of Pneumocystis jirovecii dihydrofolate reductase associated with
      failure of prophylaxis.
AB  - Most drugs used for prevention and treatment of Pneumocystis jirovecii pneumonia
      target enzymes involved in the biosynthesis of folic acid, i.e., dihydropteroate
      synthase (DHPS) and dihydrofolate reductase (DHFR). Emergence of P. jirovecii
      drug resistance has been suggested by the association between failure of
      prophylaxis with sulfa drugs and mutations in DHPS. However, data on the
      occurrence of mutations in DHFR, the target of trimethoprim and pyrimethamine,
      are scarce. We examined polymorphisms in P. jirovecii DHFR from 33 patients
      diagnosed with P. jirovecii pneumonia who were receiving prophylaxis with a DHFR
      inhibitor (n = 15), prophylaxis without a DHFR inhibitor (n = 11), or no
      prophylaxis (n = 7). Compared to the wild-type sequence present in GenBank, 19
      DHFR nucleotide substitution sites were found in 18 patients with 3 synonymous
      and 16 nonsynonymous mutations. Of 16 amino acid changes, 6 were located in
      positions conserved among distant organisms, and five of these six positions are
      probably involved in the putative active sites of the enzyme. Patients with
      failure of prophylaxis, including a DHFR inhibitor, were more likely to harbor
      nonsynonymous DHFR mutations than those who did not receive such prophylaxis (9
      of 15 patients versus 2 of 18; P = 0.008). Analysis of the rate of nonsynonymous
      versus synonymous mutations was consistent with selection of amino acid
      substitutions in patients with failure of prophylaxis including a DHFR inhibitor.
      The results suggest that P. jirovecii populations may evolve under selective
      pressure from DHFR inhibitors, in particular pyrimethamine, and that DHFR
      mutations may contribute to P. jirovecii drug resistance.

PMID- 15504857
TI  - Potential for interactions between caspofungin and nelfinavir or rifampin.
AB  - The potential for interactions between caspofungin and nelfinavir or rifampin was
      evaluated in two parallel-panel studies. In study A, healthy subjects received a
      14-day course of caspofungin alone (50 mg administered intravenously [IV] once
      daily) (n = 10) or with nelfinavir (1,250 mg administered orally twice daily) (n
      = 9) or rifampin (600 mg administered orally once daily) (n = 10). In study B, 14
      subjects received a 28-day course of rifampin (600 mg administered orally once
      daily), with caspofungin (50 mg administered IV once daily) coadministered on the
      last 14 days, and 12 subjects received a 14-day course of caspofungin alone (50
      mg administered IV once daily). The coadministration/administration alone
      geometric mean ratio for the caspofungin area under the time-concentration
      profile calculated for the 24-h period following dosing [AUC(0-24)] was as
      follows (values in parentheses are 90% confidence intervals [CIs]): 1.08 (0.93
      1.26) for nelfinavir, 1.12 (0.97-1.30) for rifampin (study A), and 1.01 (0.91
      1.11) for rifampin (study B). The shape of the caspofungin plasma profile was
      altered by rifampin, resulting in a 14 to 31% reduction in the trough
      concentration at 24 h after dosing (C(24h)), consistent with a net induction
      effect at steady state. Both the AUC and the C(24h) were elevated in the initial
      days of rifampin coadministration in study A (61 and 170% elevations,
      respectively, on day 1) but not in study B, consistent with transient net
      inhibition prior to full induction. The coadministration/administration alone
      geometric mean ratio for the rifampin AUC(0-24) on day 14 was 1.07 (90% CI, 0.83
      1.38). Nelfinavir does not meaningfully alter caspofungin pharmacokinetics.
      Rifampin both inhibits and induces caspofungin disposition, resulting in a
      reduced C(24h) at steady state. An increase in the caspofungin dose to 70 mg,
      administered daily, should be considered when the drug is coadministered with
      rifampin.

PMID- 15504858
TI  - Novel approach to characterization of combined pharmacodynamic effects of
      antimicrobial agents.
AB  - There is considerable need for new modeling approaches in the study of combined
      antimicrobial effects. Current methods based on the Loewe additivity and Bliss
      independence models are associated with implicit assumptions about the
      interacting system. To circumvent these limitations, we propose an alternative
      approach to the quantification of pharmacodynamic drug interaction (PDI). Pilot
      time-kill studies were performed with 10(8) CFU of Pseudomonas aeruginosa/ml at
      baseline with meropenem or tobramycin alone. The studies were repeated with 25
      concentration combinations of meropenem (0 to 64 mg/liter) and tobramycin (0 to
      32 mg/liter) in a five-by-five array. The data were modeled with a three
      dimensional response surface using effect summation as the basis of null
      interaction. The interaction index (Ii) is defined as the ratio of the volumes
      under the planes (VUP) of the observed and expected surfaces:
      VUP(observed)/VUP(expected). Synergy and antagonism are defined as Ii values of
      <1 and >1, respectively. In all combinations, an enhanced killing effect was seen
      compared to that of either drug at the same concentration. The most significant
      synergism was observed between 1 and 5 mg/liter of meropenem and between 1 and 4
      mg/liter of tobramycin; seven out of nine combinations had a >2-log drop compared
      to the more potent agent. The Ii was found to be 0.76 (95% confidence interval,
      0.65 to 0.91) for the concentration ranges of the agents. The results corroborate
      previous data indicating that meropenem is synergistic with an aminoglycoside
      when used in combination against P. aeruginosa. Our parametric approach to
      quantifying PDI appears robust and warrants further investigations.

PMID- 15504859
TI  - LB11058, a new cephalosporin with high penicillin-binding protein 2a affinity and
      activity in experimental endocarditis due to homogeneously methicillin-resistant
      Staphylococcus aureus.
AB  - LB11058 is a new synthetic cephalosporin with good affinity for staphylococcal
      penicillin-binding protein 2a (PBP2a). LB11058 was tested in vitro and in rats
      with experimental aortic endocarditis against three methicillin-resistant
      Staphylococcus aureus (MRSA) strains, one penicillinase-negative strain (strain
      COL), and two penicillinase-producing strains (COL-Bla+ and P8-Hom). The MICs of
      LB11058 for the organisms were 1 mg/liter. The MICs of vancomycin and ceftriaxone
      were 1 and >/=64 mg/liter, respectively. In population analysis profiles, none of
      the MRSA strains grew at >/=2 mg of LB11058/liter. Rats with endocarditis were
      treated for 5 days. LB11058 was highly bound to serum proteins in rats (>/=98%).
      However, binding was saturable above a threshold of 250 mg/liter. Therefore,
      continuous concentrations of 250 mg/liter in serum were infused to ensure a free
      fraction (>/=5 mg/liter) above the drug's MIC for the entire infusion period.
      Control treatments included simulation of human serum kinetics produced by
      intravenous vancomycin (1 g twice daily, free drug concentration above MIC,
      >/=90% of infusion period) or ceftriaxone (2 g/24 h, free drug concentrations
      above the MIC, 0% of infusion period). LB11058 successfully treated 10 of 10
      (100%) and 13 of 14 (93%) of rats infected with COL-Bla+ and P8-Hom,
      respectively. This was comparable to vancomycin (sterilization of 8 of 12 [66%]
      and 6 of 8 [75%] rats, respectively). Ceftriaxone was inactive. Low
      concentrations of LB11058 (5 and 10 mg/liter, continuously infused) in serum were
      ineffective, as predicted by the pharmacodynamic parameters. At appropriate
      doses, LB11058 was highly effective both in vitro and in vivo. This finding
      supports the development of this beta-lactam with high PBP2a affinity for the
      treatment of MRSA infections.

PMID- 15504860
TI  - Effects of valproic acid coadministration on plasma efavirenz and lopinavir
      concentrations in human immunodeficiency virus-infected adults.
AB  - Valproic acid (VPA) has the potential to benefit patients suffering from human
      immunodeficiency virus (HIV)-associated cognitive impairment. The purpose of this
      study was to determine if VPA affects the plasma concentration of efavirenz (EFV)
      or lopinavir. HIV type 1 (HIV-1)-infected patients receiving EFV or lopinavir
      ritonavir (LPV/r) had 9 or 10 blood samples drawn over 8 to 24 h of a dosing
      interval at steady state before and after receiving 250 mg of VPA twice daily for
      7 days. VPA blood samples drawn before (C(0)) and 8 h after the morning dose (8
      h) were compared to blood samples from a group of HIV-1-infected subjects who
      were taking either combined nucleoside reverse transcriptase inhibitors alone or
      had discontinued antiretroviral therapy. Pharmacokinetic parameters were
      calculated by noncompartmental analysis, and tests of bioequivalence were based
      on 90% confidence intervals (CIs) for ratios or differences. The geometric mean
      ratio (GMR) (90% CI) of the areas under the concentration-time curve from 0 to 24
      h (AUC(0-24)s) of EFV (n = 11) with and without VPA was 1.00 (0.85, 1.17). The
      GMR (90% CI) of the AUC(0-8)s of LPV (n = 8) with and without VPA was 1.38 (0.98,
      1.94). The differences (90% CI) in mean C(0) and 8-h VPA concentrations versus
      the control (n = 11) were -1.0 (-9.4, 7.4) microg/ml and -2.1 (-11.1, 6.9)
      microg/ml for EFV (n = 10) and -5.0 (-13.2, 3.3) microg/ml and -6.7 (-17.6, 4.2)
      microg/ml for LPV/r (n = 11), respectively. EFV administration alone is
      bioequivalent to EFV and VPA coadministration. LPV concentrations tended to be
      higher when the drug was combined with VPA. Results of VPA comparisons fail to
      raise concern that coadministration with EFV or LPV/r will significantly
      influence trough concentrations of VPA.

PMID- 15504861
TI  - Maternal-fetal transfer and amniotic fluid accumulation of nucleoside analogue
      reverse transcriptase inhibitors in human immunodeficiency virus-infected
      pregnant women.
AB  - This study was performed to investigate placental transfer of nucleoside analogue
      reverse transcriptase inhibitors (NRTIs) and their concentrations in amniotic
      fluid when given to human immunodeficiency virus (HIV)-infected pregnant women. A
      total of 100 HIV type 1-infected mothers receiving antiretroviral therapy,
      including one or more NRTIs, for clinical indications at the time of delivery
      were enrolled. Maternal blood samples and amniotic fluid were obtained during
      delivery or cesarean section, and paired cord blood samples were obtained by
      venipuncture immediately after delivery. Drug concentrations were measured by
      using high-performance liquid chromatography. A significant relationship between
      concentrations in maternal and cord plasma samples was found for zidovudine,
      lamivudine, stavudine, and didanosine. The ratio between the concentrations in
      cord and maternal plasma samples (R) was high for zidovudine (R = 1.22), its
      glucuronide metabolite (3'-azido-3'-deoxythymidine-beta-d-glucuronide) (R =
      1.01), stavudine (R = 1.32), lamivudine (R = 0.93), and abacavir (R = 1.03) and
      was low for didanosine (R = 0.38). The ratio between the concentrations in
      amniotic fluid and cord plasma samples was high for zidovudine (R = 2.24), its
      glucuronide metabolite (R = 2.83), stavudine (R = 4.87), and lamivudine (R =
      3.99) and was lower for didanosine (R = 1.14). These findings indicate that most
      NRTIs cross the placenta by simple diffusion and are concentrated in the amniotic
      fluid, probably through fetal urinary excretion. The efficacy or toxicity of
      NRTIs may vary according to placental transfer.

PMID- 15504862
TI  - Inhibition of adherence and killing of Candida albicans with a 23-Mer peptide
      (Fn/23) with dual antifungal properties.
AB  - Candida albicans adheres to host tissue and then proliferates in order to
      establish a commensal as well as a pathogenic state. Specific adherence to
      proteins is provided by several surface adhesins of Candida. Two well-studied
      proteins, Als1p and Als5p, do not require energy for adherence to occur (dead as
      well as living cells adhere) and have a multiplier effect of cell-cell
      aggregation that mediates the formation of microcolonies of Candida cells. The
      entire process is spontaneous, reversible, and stable for physiologically
      relevant chemical and physical forces. This adherence process is inhibited by the
      addition of free peptide ligands, including a 23-mer derived from fibronectin
      (Fn/23) that binds to the adhesins through H bond formation. Adherence was
      measured by determining the number of yeast cells that adhered to 90-microm
      diameter polyethylene glycol (PEG) beads with a 7-mer peptide (KLRIPSV)
      synthesized on the surfaces of the beads. The concentration of the Fn/23 peptide
      that inhibited the adherence of cells to the peptide-coated beads by 50% was 4 to
      5 microM, and the magnitudes of adherence were similar regardless of the presence
      or absence of physiologic salt concentrations. The minimum fungicidal
      concentration of Fn/23 was 2 to 4 microM in water, but there was no killing in
      physiologic salt concentrations. Peptides from the C and N termini or the center
      sequence of Fn/23 had no effect on inhibition of adherence and little effect on
      fungal viability. The fungicidal effect was similar to that seen with 23-, 19-,
      and 18-mer peptides derived from porcine myeloid cells, a Helicobacter pylori
      ribosomal protein, and a hybrid of cecropin and magainin, respectively. However,
      these fungicidal peptides did not inhibit C. albicans adherence to the peptide
      coated PEG beads. This dual property of Fn/23, i.e., inhibition of adherence and
      killing of C. albicans, may provide important adjuvant effects in the treatment
      of disease caused by this fungus.

PMID- 15504863
TI  - Delivery of granulocyte-macrophage colony-stimulating factor in bioadhesive
      hydrogel stimulates migration of dendritic cells in models of human
      papillomavirus-associated (pre)neoplastic epithelial lesions.
AB  - Because of the central role of dendritic cells and/or Langerhans cells(DC/LC) in
      the induction of cellular immune responses, pharmacological agents that modulate
      the recruitment of these cells might have a clinical interest. The present study
      was designed to evaluate the capacity of several pharmaceutical formulations to
      topically deliver granulocyte-macrophage colony-stimulating factor (GM-CSF) on
      human papillomavirus (HPV)-associated genital (pre)neoplastic lesions. The
      formulations were evaluated for their bioactivity and for their potential to
      recruit DC in organotypic cultures of HPV-transformed keratinocytes. We found
      that a bioadhesive polycarbophil gel (Noveon) at pH 5.5 is able to maintain the
      bioactivity of GM-CSF at 4 or 37 degrees C for at least 7 days, whereas a
      decreased activity of GM-CSF was observed when the molecule is included in other
      polymer gels. GM-CSF incorporated in the polycarbophil gel was also a potent
      factor in enhancing the colonization of DC into organotypic cultures of HPV
      transformed keratinocytes since the infiltration of DC in the in vitro-formed
      (pre)neoplastic epithelium was very low under basal conditions and dramatically
      increased in the presence of GM-CSF gel. We next demonstrated that GM-CSF
      incorporated in polycarbophil gel induces the recruitment of human DC in a human
      (pre)neoplastic epithelium grafted into NOD/SCID mice. The efficacy of GM-CSF in
      this formulation was equivalent to that observed with liquid GM-CSF. These
      results suggest that GM-CSF incorporated in polycarbophil gel could play an
      important role in the recruitment of DC/LC in mucosal surfaces and be useful as a
      new immunotherapeutic approach for genital HPV-associated (pre)neoplastic
      lesions.

PMID- 15504864
TI  - N-substituted pyrrole derivatives as novel human immunodeficiency virus type 1
      entry inhibitors that interfere with the gp41 six-helix bundle formation and
      block virus fusion.
AB  - A recently approved peptidic human immunodeficiency virus type 1 (HIV-1) fusion
      inhibitor, T-20 (Fuzeon; Trimeris Inc.), has shown significant promise in
      clinical application for treating HIV-1-infected individuals who have failed to
      respond to the currently available antiretroviral drugs. However, T-20 must be
      injected twice daily and is too expensive. Therefore, it is essential to develop
      orally available small molecule HIV-1 fusion inhibitors. By screening a chemical
      library consisting of "drug-like" compounds, we identified two N-substituted
      pyrroles, designated NB-2 and NB-64, that inhibited HIV-1 replication at a low
      micromolar range. The absence of the COOH group in NB-2 and NB-64 resulted in a
      loss of anti-HIV-1 activity, suggesting that this acid group plays an important
      role in mediating the antiviral activity. NB-2 and NB-64 inhibited HIV-1 fusion
      and entry by interfering with the gp41 six-helix bundle formation and disrupting
      the alpha-helical conformation. They blocked a d-peptide binding to the
      hydrophobic pocket on surface of the gp41 internal trimeric coiled-coil domain.
      Computer-aided molecular docking analysis has shown that they fit inside the
      hydrophobic pocket and that their COOH group interacts with a positively charged
      residue (K574) around the pocket to form a salt bridge. These results suggest
      that NB-2 and NB-64 may bind to the gp41 hydrophobic pocket through hydrophobic
      and ionic interactions and block the formation of the fusion-active gp41 core,
      thereby inhibiting HIV-1-mediated membrane fusion and virus entry. Therefore, NB
      2 and NB-64 can be used as lead compounds toward designing and developing more
      potent small molecule HIV-1 fusion inhibitors targeting gp41.

PMID- 15504865
TI  - Usnic acid, a natural antimicrobial agent able to inhibit bacterial biofilm
      formation on polymer surfaces.
AB  - In modern medicine, artificial devices are used for repair or replacement of
      damaged parts of the body, delivery of drugs, and monitoring the status of
      critically ill patients. However, artificial surfaces are often susceptible to
      colonization by bacteria and fungi. Once microorganisms have adhered to the
      surface, they can form biofilms, resulting in highly resistant local or systemic
      infections. At this time, the evidence suggests that (+)-usnic acid, a secondary
      lichen metabolite, possesses antimicrobial activity against a number of
      planktonic gram-positive bacteria, including Staphylococcus aureus, Enterococcus
      faecalis, and Enterococcus faecium. Since lichens are surface-attached
      communities that produce antibiotics, including usnic acid, to protect themselves
      from colonization by other bacteria, we hypothesized that the mode of action of
      usnic acid may be utilized in the control of medical biofilms. We loaded (+)
      usnic acid into modified polyurethane and quantitatively assessed the capacity of
      (+)-usnic acid to control biofilm formation by either S. aureus or Pseudomonas
      aeruginosa under laminar flow conditions by using image analysis. (+)-Usnic acid
      loaded polymers did not inhibit the initial attachment of S. aureus cells, but
      killing the attached cells resulted in the inhibition of biofilm. Interestingly,
      although P. aeruginosa biofilms did form on the surface of (+)-usnic acid-loaded
      polymer, the morphology of the biofilm was altered, possibly indicating that (+)
      usnic acid interfered with signaling pathways.

PMID- 15504866
TI  - Analysis of mupirocin resistance and fitness in Staphylococcus aureus by
      molecular genetic and structural modeling techniques.
AB  - Chromosomal resistance to mupirocin in clinical isolates of Staphylococcus aureus
      arises from V(588)F or V(631)F mutations in isoleucyl-tRNA synthetase (IRS).
      Whether these are the only IRS mutations that confer mupirocin resistance or
      simply those that survive in the clinic is unknown. Mupirocin-resistant mutants
      of S. aureus 8325-4 were therefore generated to examine their ileS genotypes and
      the in vitro and in vivo fitness costs associated with them before and after
      compensatory evolution. Most spontaneous first-step mupirocin-resistant mutants
      carried V(588)F or V(631)F mutations in IRS, but a new mutation (G(593)V) was
      also identified. Second-step mutants carried combinations of previously
      identified IRS mutations (e.g., V(588)F/V(631)F and G(593)V/V(631)F), but
      additional combinations also occurred involving novel mutations (R(816)C, H(67)Q,
      and F(563)L). First-step mupirocin-resistant mutants were not associated with
      substantial fitness costs, a finding that is consistent with the occurrence of
      V(588)F or V(631)F mutations in the IRS of clinical strains. Second-step mutants
      were unfit, but fitness could be restored by subculture in the absence of
      mupirocin. In most cases, this was the result of compensatory mutations that also
      suppressed mupirocin resistance (e.g., A(196)V, E(190)K, and E(195)K), despite
      retention of the original mutations conferring resistance. Structural
      explanations for mupirocin resistance and loss of fitness were obtained by
      molecular modeling of mutated IRS enzymes, which provided data on mupirocin
      binding and interaction with the isoleucyl-AMP reactive intermediate.

PMID- 15504867
TI  - Molecular mechanisms of primary resistance to flucytosine in Candida albicans.
AB  - Primary resistance in Candida albicans to flucytosine (5-FC) was investigated in
      25 strains by identifying and sequencing the genes FCA1, FUR1, FCY21, and FCY22,
      which code for cytosine deaminase, uracil phosphoribosyltransferase (UPRT), and
      two purine-cytosine permeases, respectively. These proteins are involved in
      pyrimidine salvage and 5-FC metabolism. An association between a polymorphic
      nucleotide and resistance to 5-FC was found within FUR1 where the substitution of
      cytidylate for thymidylate at nucleotide position 301 results in the replacement
      of arginine with cysteine at amino acid position 101 in UPRT. Isolates that are
      homozygous for this mutation display increased levels of resistance to 5-FC,
      whereas heterozygous isolates have reduced susceptibility. Three-dimensional
      protein modeling of UPRT suggests that the Arg101Cys mutation disturbs the
      quaternary structure of the enzyme, which is postulated to compromise optimal
      enzyme activity. A single resistant isolate, lacking the above polymorphism in
      FUR1, has a homozygous polymorphism in FCA1 that results in a glycine-to
      aspartate substitution at position 28 in cytosine deaminase.

PMID- 15504868
TI  - In vitro combination of amdoxovir and the inosine monophosphate dehydrogenase
      inhibitors mycophenolic acid and ribavirin demonstrates potent activity against
      wild-type and drug-resistant variants of human immunodeficiency virus type 1.
AB  - Amdoxovir [(-)-beta-d-2,6-diaminopurine dioxolane (DAPD)] is a nucleoside
      analogue reverse transcriptase inhibitor of human immunodeficiency virus type 1
      (HIV-1) replication. DAPD is deaminated by adenosine deaminase to the guanosine
      analogue dioxolane guanosine (DXG), which is subsequently phosphorylated to the
      corresponding 5' triphosphate (DXG-TP). DXG-TP competes with the natural
      substrate dGTP for binding to the enzyme-nucleic acid complex. Mycophenolic acid
      (MPA) and ribavirin (RBV), inhibitors of inosine monophosphate dehydrogenase
      (IMPDH), inhibit the de novo synthesis of guanine nucleotides, including dGTP.
      Reducing the intracellular levels of dGTP would be expected to augment the
      antiviral activity of analogues of deoxyguanosine. In this study we examined the
      effect of MPA and RBV on the anti-HIV activity of DAPD and DXG. When tested
      against wild-type virus, both MPA and RBV decreased the 50% effective
      concentration (EC(50)) for DXG by at least 10-fold. In contrast, both MPA and RBV
      increase the EC(50) value for zidovudine. MPA and RBV completely reversed the
      resistance to DXG observed with HIV isolates containing mutations which confer
      partial resistance to DAPD and DXG. Similarly, when tested against a mutant virus
      fully resistant to inhibition by DAPD (K65R/Q151M), MPA and RBV reduced the
      EC(50) for DAPD to within twofold of that for the wild type. The combination of
      MPA or RBV with DAPD or DXG did not result in increased cytotoxicity or reduced
      levels of mitochondrial DNA when tested at physiologically relevant
      concentrations. These studies suggest a potential role for the use of IMPDH
      inhibitors in combination therapy with amdoxovir in the treatment of HIV.

PMID- 15504869
TI  - Platelet microbicidal protein 1: structural themes of a multifunctional
      antimicrobial peptide.
AB  - Mammalian platelets release platelet microbicidal proteins (PMPs) as components
      of their antimicrobial armamentarium. The present studies defined the structure
      of PMP-1 and examined its structure-activity relationships. Amino acid sequencing
      and mass spectroscopy demonstrated that distinct N-terminal polymorphism variants
      of PMP-1 isolated from nonstimulated or thrombin-stimulated platelets arise from
      a single PMP-1 propeptide. Sequence data (NH(2)
      [S]D(1)DPKE(5)SEGDL(10)HCVCV(15)KTTSL(20) . . .) enabled cloning of PMP-1 from
      bone marrow and characterization of its full-length cDNA. PMP-1 is translated as
      a 106-amino-acid precursor and is processed to yield 73-residue (8,053 Da) and 72
      residue (7,951-Da) variants. Searches with the BLAST program and sequence
      alignments demonstrated the homology of PMP-1 to members of the mammalian
      platelet factor 4 (PF-4) family of proteins. On the basis of phylogenetic
      relatedness, congruent sequence motifs, and predicted three-dimensional
      structures, PMP-1 shares the greatest homology with human PF-4 (hPF-4). By
      integration of its structural and antimicrobial properties, these results
      establish the identity of PMP-1 as a novel rabbit analogue of the microbicidal
      chemokine (kinocidin) hPF-4. These findings advance the hypothesis that stimuli
      in the setting of infection prompt platelets to release PF-4-class or related
      kinocidins, which have structures consistent with their likely multiple roles
      that bridge molecular and cellular mechanisms of antimicrobial host defense.

PMID- 15504870
TI  - In vitro evolution of itraconazole resistance in Aspergillus fumigatus involves
      multiple mechanisms of resistance.
AB  - We investigated the evolution of resistance to the antifungal drug itraconazole
      in replicate populations of Aspergillus fumigatus that were founded from a strain
      with a genotype of sensitivity to a single drug and then propagated under uniform
      conditions. For each population, conidia were serially transferred 10 times to
      agar medium either with or without itraconazole. After 10 transfers in medium
      supplemented with itraconazole, 10 itraconazole-resistant mutant strains were
      isolated from two populations. These mutant strains had different growth rates
      and different levels of itraconazole resistance. Analysis of the ergosterol
      contents of these mutants showed that they accumulate ergosterol when they are
      grown in the presence of itraconazole. The replacement of the CYP51A gene of the
      wild-type strain changed the susceptibility pattern of this strain to one of
      itraconazole resistance only when CYP51A genes with N22D and M220I mutations were
      used as selectable marker genes. Real-time quantitative reverse transcription-PCR
      was used to assess the levels of expression of the Afumdr1, Afumdr2, Afumdr3,
      Afumdr4, AtrF transporter, CYP51A, and CYP51B genes in these mutant strains. Most
      mutants showed either constitutive high-level expression or induction upon
      exposure of Afumdr3, Afumdr4, and AtrF to itraconazole. Our results suggest that
      overexpression of drug efflux pumps and/or selection of drug target site
      mutations are at least partially responsible for itraconazole resistance and
      could be considered mechanisms for the emergence of clinical resistance to this
      drug.

PMID- 15504871
TI  - Anti-Aspergillus fumigatus efficacy of pentraxin 3 alone and in combination with
      antifungals.
AB  - The collectin pentraxin 3 (PTX3) is an essential component of host resistance to
      pulmonary aspergillosis. Here we examined the protective effects of
      administration of PTX3 alone or together with deoxycholate amphotericin B
      (Fungizone) or liposomal amphotericin B (AmBisome) against invasive aspergillosis
      in a murine model of allogeneic bone marrow transplantation. PTX3, alone or in
      combination with the polyenes, was given intranasally or parenterally either
      before, in concomitance with, or after the intranasal infection with Aspergillus
      fumigatus conidia. Mice were monitored for resistance to infection and parameters
      of innate and adaptive T-helper immunity. The results showed the following: (i)
      complete resistance to infection and reinfection was observed in mice treated
      with PTX3 alone; (ii) the protective effect of PTX3 was similar or superior to
      that observed with liposomal amphotericin B or deoxycholate amphotericin B,
      respectively; (iii) protection was associated with accelerated recovery of lung
      phagocytic cells and T-helper-1 lymphocytes and concomitant decrease of
      inflammatory pathology; and (iv) PTX3 potentiated the therapeutic efficacy of
      suboptimal doses of either antimycotic drug. Together, these data suggest the
      potential therapeutic use of PTX3 either alone or as an adjunctive therapy in A.
      fumigatus infections.

PMID- 15504872
TI  - Dose-dependent resorption of quinine after intrarectal administration to children
      with moderate Plasmodium falciparum malaria.
AB  - The pharmacokinetics of increasing doses of an intrarectal Cinchona alkaloid
      combination containing 96.1% quinine, 2.5% quinidine, 0.68% cinchonine, and 0.67%
      cinchonidine (Quinimax) was compared to that of parenteral regimens in 60
      children with moderate malaria. Quinine exhibited a nonlinear pharmacokinetics,
      suggesting a saturation of rectal resorption. When early rejections appeared,
      blood quinine concentrations decreased by 30 to 50% and were restored by an
      immediate half-dose administration of the drug. Rectal administration of doses of
      16 or 20 mg/kg of body weight led to concentration-time profiles in blood similar
      to those of parenteral regimens and could be an early treatment of childhood
      malaria.

PMID- 15504873
TI  - Evidence for biliary excretion of vancomycin into stool during intravenous
      therapy: potential implications for rectal colonization with vancomycin-resistant
      enterococci.
AB  - Sixty-three stool samples and five bile samples were prospectively collected from
      33 patients receiving intravenous vancomycin therapy and were quantitatively
      analyzed for vancomycin by a competitive immunoassay. Vancomycin was excreted via
      bile into the stools of almost all patients at concentrations of 3.3 to 94.8
      microg/ml after >/=5 days of a therapy of 1 g every 12 h.

PMID- 15504874
TI  - Activity of OPT-80, a novel macrocycle, compared with those of eight other agents
      against selected anaerobic species.
AB  - Agar dilution MIC was used to compare activities of OPT-80, linezolid,
      vancomycin, teicoplanin, quinupristin/dalfopristin, amoxicillin/clavulanate,
      imipenem, clindamycin, and metronidazole against 350 gram-positive and -negative
      anaerobes. OPT-80 was active against gram-positive strains only, especially
      Clostridium spp. (85 strains tested, including 21 strains of C. difficile), with
      MICs ranging between </=0.016 and 0.25 microg/ml.

PMID- 15504875
TI  - Community-onset disease caused by Citrobacter freundii producing a novel CTX-M
      beta-lactamase, CTX-M-30, in Canada.
AB  - Strains of Citrobacter freundii intermediate to cefotaxime but sensitive to
      ceftazidime were isolated from four different patients in Canada. Sequencing of
      PCR products by use of CTX-M-specific primers revealed a new combination of four
      amino acid substitutions. This new gene was designated bla(CTX-M-30) and was
      encoded on a 3-kb plasmid. The pI of CTX-M-30 was 8.0.

PMID- 15504876
TI  - Plasmid-mediated carbapenem-hydrolyzing enzyme KPC-2 in an Enterobacter sp.
AB  - A strain of an Enterobacter sp. with reduced susceptibility to imipenem, which
      produced a plasmid-mediated class A carbapenem-hydrolyzing enzyme, KPC-2 beta
      lactamase, was isolated from a patient with sepsis at a Boston hospital. This is
      the first report of the production of a plasmid-encoded KPC-2 beta-lactamase by
      an Enterobacter sp.

PMID- 15504877
TI  - Altered susceptibility of Candida glabrata bloodstream isolates to triazoles at
      clinically relevant pH values: comparison of the NCCLS M27-A2, Sensititre
      YeastOne, and Etest methods.
AB  - We studied the MICs of triazoles against 15 Candida glabrata clinical isolates by
      the NCCLS M27-A2, Sensititre YeastOne, and Etest methods by using media at pHs
      6.0, 7.0, and 7.4. Thirteen isolates were less susceptible to triazoles at pH 6.0
      and more susceptible to triazoles at pH 7.4 compared to pH 7.0.

PMID- 15504878
TI  - Antibiotic susceptibility in neonatal invasive isolates of Streptococcus
      agalactiae in a 2-year nationwide surveillance study in Germany.
AB  - The antimicrobial susceptibility of 296 invasive neonatal group B streptococcus
      isolates from a nationwide 2-year surveillance study in Germany was investigated.
      All isolates were susceptible to beta-lactams, linezolid, quinupristin
      dalfopristin, and vancomycin. Erythromycin and clindamycin resistance was found
      in 10.1 and 5.7%, respectively. The ermB, ermTR, or mefA gene was detected in all
      but one of the erythromycin-resistant isolates.

PMID- 15504879
TI  - Novel mutations within the embB gene in ethambutol-susceptible clinical isolates
      of Mycobacterium tuberculosis.
AB  - Genetic analysis of the embB gene revealed mutations in 17 (68%) of 25 ethambutol
      (EMB) resistant isolates (M306I, M306V, M306L, Q497R) but also in 4 (20%) of 20
      EMB-susceptible isolates of Mycobacterium tuberculosis, namely, an ATG-->ATM
      substitution resulting in M306I, G406N, and the novel alterations M423I and
      A659T.

PMID- 15504880
TI  - Antimicrobial and antileishmanial activities of hypocrellins A and B.
AB  - Hypocrellins A and B were evaluated for in vitro antimicrobial and
      antileishmanial activities. Hypocrellin A exhibited promising activity against
      Candida albicans and moderate activity against Staphylococcus aureus, methicillin
      resistant S. aureus, Pseudomonas aeruginosa, and Mycobacterium intracellulare.
      Hypocrellin B showed weak antimicrobial activities. Hypocrellin A exhibited
      potent antileishmanial activity, while hypocrellin B was only moderately active.
      These results of promising antifungal and antileishmanial activity of hypocrellin
      A may be useful for further structure-activity relationship and in vivo studies.

PMID- 15504881
TI  - In vitro pharmacodynamic characteristics of amphotericin B, caspofungin,
      fluconazole, and voriconazole against bloodstream isolates of infrequent Candida
      species from patients with hematologic malignancies.
AB  - Time-kill and postantifungal effect (PAFE) of amphotericin B, caspofungin,
      fluconazole, and voriconazole were determined against clinical isolates of
      Candida guilliermondii, Candida kefyr, and Candida lusitaniae. Azoles displayed
      fungistatic activity and no measurable PAFE, regardless of the concentration
      tested. Amphotericin B and caspofungin demonstrated concentration-dependent
      fungicidal activity, although amphotericin B only produced a significant dose
      dependent PAFE against all isolates tested.

PMID- 15504882
TI  - Evaluation of a colorimetric antifungal susceptibility test by using 2,3-diphenyl
      5-thienyl-(2)-tetrazolium chloride.
AB  - A colorimetric antifungal susceptibility test was performed using 2,3-diphenyl-5
      thienyl-(2)-tetrazolium chloride. Among 24 strains of Candida species, no
      trailing growth was found. In 22 and 20 strains, the MICs obtained in the
      colorimetric assay were within two dilutions of those obtained by the National
      Committee for Clinical Laboratory Standards method for ketoconazole and
      itraconazole, respectively.

PMID- 15504884
TI  - Antimicrobial susceptibility patterns among viridans group streptococcal isolates
      from infective endocarditis patients from 1971 to 1986 and 1994 to 2002.
AB  - To determine whether changes in antimicrobial resistance have occurred among
      viridans group streptococci, we retrospectively examined 50 viridans group
      streptococcal isolates recovered from patients with infective endocarditis over 3
      decades. Resistance rates (percent resistant isolates 1971 to 1986 and 1994 to
      2002) were as follows: levofloxacin, 0 and 9; penicillin and clindamycin, 0 and
      4; and erythromycin and azithromycin, 11 and 26, respectively.

PMID- 15504883
TI  - Quinolone-resistant Haemophilus influenzae: determination of mutant selection
      window for ciprofloxacin, garenoxacin, levofloxacin, and moxifloxacin.
AB  - Stepwise selection of ciprofloxacin-resistant Haemophilus influenzae mutants
      produced first-, second-, third-, and fourth-step substitutions in GyrA (S84Y),
      ParC (S84R), GyrA (D88N), and ParC (E88K), respectively. Successive mutations
      raised the mutant selection window. The wild-type selection window for
      garenoxacin, levofloxacin, and moxifloxacin was also measured.

PMID- 15504885
TI  - SHV-49, a novel inhibitor-resistant beta-lactamase in a clinical isolate of
      Klebsiella pneumoniae.
AB  - A clinical strain of Klebsiella pneumoniae carried the bla(SHV-49) gene, encoding
      a novel inhibitor-resistant beta-lactamase of pI 7.6, derived from SHV-1 by the
      single substitution M69I. It also harbored a gene differing from bla(SHV-11) by
      four silent mutations and coding for a penicillinase. Both genes were chromosome
      located and might represent either a species-specific gene or an acquired
      resistance gene.

PMID- 15504886
TI  - In vitro susceptibilities of Mycoplasma hyopneumoniae field isolates.
AB  - The in vitro susceptibilities of 21 Mycoplasma hyopneumoniae field isolates were
      determined using a broth microdilution technique. One isolate showed acquired
      resistance to lincomycin, tilmicosin, and tylosin, while five isolates were
      resistant to flumequine and enrofloxacin. Acquired resistance against these
      antimicrobials in M. hyopneumoniae field isolates was not reported previously.

PMID- 15504887
TI  - Decreased bioavailability of rifampin and other antituberculosis drugs in
      patients with advanced human immunodeficiency virus disease.
AB  - We evaluated the effects of human immunodeficiency virus (HIV) disease on
      pharmacokinetics of antituberculosis medications by measuring concentrations of
      isoniazid and rifampin in blood and of pyrazinamide and ethambutol in urine. Peak
      concentration and exposure were reduced for rifampin, and rapid acetylators of
      isoniazid had lower drug levels. HIV and HIV-tuberculosis patients who have
      diarrhea and cryptosporidial infection exhibit decreased bioavailability of
      antituberculosis drugs.

PMID- 15504888
TI  - Pharmacokinetics of indinavir at 800, 600, and 400 milligrams administered with
      ritonavir at 100 milligrams and efavirenz in ethnic chinese patients infected
      with human immunodeficiency virus.
AB  - We assessed the pharmacokinetics of three different doses of indinavir in five
      patients. All doses achieved trough concentrations above efficacy thresholds.
      Toxic trough concentrations were observed in all patients receiving 800 mg, in
      two patients receiving 600 mg, and in none receiving 400 mg. Indinavir at 400 mg
      may be efficacious and less toxic in patients taking ritonavir and efavirenz.

PMID- 15504889
TI  - Activity of tigecycline (GAR-936) against Acinetobacter baumannii strains,
      including those resistant to imipenem.
AB  - We determined the in vitro activities of tigecycline and imipenem against 49
      isolates of Acinetobacter baumannii, including those resistant to imipenem. The
      MIC at which 50% of the isolates were inhibited (MIC(50)) and the MIC(90) for
      tigecycline and imipenem were 2 and 2 mg/liter and 32 and 128 mg/liter,
      respectively, with 92 and 20%, respectively, of the strains being susceptible.
      Tigecycline did not show bactericidal activity in the time-kill studies (n = 9
      strains). Imipenem showed bactericidal activity against seven out of nine
      strains. These in vitro results show that tigecycline has good in vitro
      bacteriostatic activity against A. baumannii, including strains resistant to
      imipenem.

PMID- 15504890
TI  - Pharmacodynamics of ceftazidime plus the serine beta-lactamase inhibitor AM-112
      against Escherichia coli containing TEM-1 and CTX-M-1 beta-lactamases.
AB  - A strain of Escherichia coli containing TEM-1 and CTX-M-1 was tested in an in
      vitro pharmacokinetic model against ceftazidime with and without AM-112, a serine
      beta-lactamase inhibitor. Ceftazidime alone was less effective than ceftazidime
      plus AM-112, and a single dose was more effective than three fractionated doses.

PMID- 15504891
TI  - Nonisotopic, semiautomated plasmodium falciparum bioassay for measurement of
      antimalarial drug levels in serum or plasma.
AB  - A simple, nonisotopic, semiautomated bioassay for the measurement of antimalarial
      drug levels in plasma or serum based on the quantitation of histidine-rich
      protein II in malaria culture is presented. The assay requires only small sample
      volumes and was found to be highly sensitive and reproducible. The results
      closely paralleled those obtained with isotopic bioassays (R = 0.988, P < 0.001)
      and high-performance liquid chromatography-electrochemical detection (R = 0.978,
      P < 0.001).

PMID- 15504892
TI  - Comparison of simultaneous splenic sample PCR with blood sample PCR for diagnosis
      and treatment of experimental Ehrlichia canis infection.
AB  - This report presents evidence that dogs recover from acute canine monocytic
      ehrlichiosis (CME) after 16 days of doxycycline treatment (10 mg/kg of body
      weight every 24 h). Blood PCR was as valuable as splenic aspirate PCR for early
      diagnosis of acute CME. Splenic aspirate PCR was, however, superior to blood PCR
      for the evaluation of ehrlichial elimination.

PMID- 15504893
TI  - The echinocandin "target" identified by cross-linking is a homolog of Pil1 and
      Lsp1, sphingolipid-dependent regulators of cell wall integrity signaling.

PMID- 15504894
TI  - First report of Salmonella isolates with the DHA-1 AmpC beta-lactamase in the
      United Kingdom.

PMID- 15504895
TI  - Uncommon association of T69 3-base-pair insertion plus Q151M multidrug resistance
      mutations in human immunodeficiency virus type 1 reverse transcriptase.

PMID- 15504897
TI  - Modal gating of human CaV2.1 (P/Q-type) calcium channels: II. the b mode and
      reversible uncoupling of inactivation.
AB  - The single channel gating properties of human CaV2.1 (P/Q-type) calcium channels
      were investigated with cell-attached patch-clamp recordings on HEK293 cells
      stably expressing these calcium channels. Human CaV2.1 channels showed a complex
      modal gating, which is described in this and the preceding paper (Luvisetto, S.,
      T. Fellin, M. Spagnolo, B. Hivert, P.F. Brust, M.M. Harpold, K.A. Stauderman,
      M.E. Williams, and D. Pietrobon. 2004. J. Gen. Physiol. 124:445-461). Here, we
      report the characterization of the so-called b gating mode. A CaV2.1 channel in
      the b gating mode shows a bell-shaped voltage dependence of the open probability,
      and a characteristic low open probability at high positive voltages, that
      decreases with increasing voltage, as a consequence of both shorter mean open
      time and longer mean closed time. Reversible transitions of single human CaV2.1
      channels between the b gating mode and the mode of gating in which the channel
      shows the usual voltage dependence of the open probability (nb gating mode) were
      much more frequent (time scale of seconds) than those between the slow and fast
      gating modes (time scale of minutes; Luvisetto et al., 2004), and occurred
      independently of whether the channel was in the fast or slow mode. We show that
      the b gating mode produces reversible uncoupling of inactivation in human CaV2.1
      channels. In fact, a CaV2.1 channel in the b gating mode does not inactivate
      during long pulses at high positive voltages, where the same channel in both fast
      nb and slow-nb gating modes inactivates relatively rapidly. Moreover, a CaV2.1
      channel in the b gating mode shows a larger availability to open than in the nb
      gating modes. Regulation of the complex modal gating of human CaV2.1 channels
      could be a potent and versatile mechanism for the modulation of synaptic strength
      and plasticity as well as of neuronal excitability and other postsynaptic Ca2+
      dependent processes.

PMID- 15504896
TI  - Modal gating of human CaV2.1 (P/Q-type) calcium channels: I. The slow and the
      fast gating modes and their modulation by beta subunits.
AB  - The single channel gating properties of human CaV2.1 (P/Q-type) calcium channels
      and their modulation by the auxiliary beta1b, beta2e, beta3a, and beta4a subunits
      were investigated with cell-attached patch-clamp recordings on HEK293 cells
      stably expressing human CaV2.1 channels. These calcium channels showed a complex
      modal gating, which is described in this and the following paper (Fellin, T., S.
      Luvisetto, M. Spagnolo, and D. Pietrobon. 2004. J. Gen. Physiol. 124:463-474).
      Here, we report the characterization of two modes of gating of human CaV2.1
      channels, the slow mode and the fast mode. A channel in the two gating modes
      differs in mean closed times and latency to first opening (both longer in the
      slow mode), in voltage dependence of the open probability (larger depolarizations
      are necessary to open the channel in the slow mode), in kinetics of inactivation
      (slower in the slow mode), and voltage dependence of steady-state inactivation
      (occurring at less negative voltages in the slow mode). CaV2.1 channels
      containing any of the four beta subtypes can gate in either the slow or the fast
      mode, with only minor differences in the rate constants of the transitions
      between closed and open states within each mode. In both modes, CaV2.1 channels
      display different rates of inactivation and different steady-state inactivation
      depending on the beta subtype. The type of beta subunit also modulates the
      relative occurrence of the slow and the fast gating mode of CaV2.1 channels;
      beta3a promotes the fast mode, whereas beta4a promotes the slow mode. The
      prevailing mode of gating of CaV2.1 channels lacking a beta subunit is a gating
      mode in which the channel shows shorter mean open times, longer mean closed
      times, longer first latency, a much larger fraction of nulls, and activates at
      more positive voltages than in either the fast or slow mode.

PMID- 15504898
TI  - Structure-function relations of the first and fourth predicted extracellular
      linkers of the type IIa Na+/Pi cotransporter: I. Cysteine scanning mutagenesis.
AB  - The putative first intracellular and third extracellular linkers are known to
      play important roles in defining the transport properties of the type IIa Na+
      coupled phosphate cotransporter (Kohler, K., I.C. Forster, G. Stange, J. Biber,
      and H. Murer. 2002b. J. Gen. Physiol. 120:693-705). To investigate whether other
      stretches that link predicted transmembrane domains are also involved, the
      substituted cysteine accessibility method (SCAM) was applied to sites in the
      predicted first and fourth extracellular linkers (ECL-1 and ECL-4). Mutants based
      on the wild-type (WT) backbone, with substituted novel cysteines, were expressed
      in Xenopus oocytes, and their function was assayed by isotope uptake and
      electrophysiology. Functionally important sites were identified in both linkers
      by exposing cells to membrane permeant and impermeant methanethiosulfonate (MTS)
      reagents. The cysteine modification reaction rates for sites in ECL-1 were faster
      than those in ECL-4, which suggested that the latter were less accessible from
      the extracellular medium. Generally, a finite cotransport activity remained at
      the end of the modification reaction. The change in activity was due to altered
      voltage-dependent kinetics of the Pi-dependent current. For example, cys
      substitution at Gly-134 in ECL-1 resulted in rate-limiting, voltage-independent
      cotransport activity for V < or = -80 mV, whereas the WT exhibited a linear
      voltage dependency. After cys modification, this mutant displayed a supralinear
      voltage dependency in the same voltage range. The opposite behavior was
      documented for cys substitution at Met-533 in ECL-4. Modification of cysteines at
      two other sites in ECL-1 (Ile-136 and Phe-137) also resulted in supralinear
      voltage dependencies for hyperpolarizing potentials. Taken together, these
      findings suggest that ECL-1 and ECL-4 may not directly form part of the transport
      pathway, but specific sites in these linkers can interact directly or indirectly
      with parts of NaPi-IIa that undergo voltage-dependent conformational changes and
      thereby influence the voltage dependency of cotransport.

PMID- 15504899
TI  - Structure-function relations of the first and fourth extracellular linkers of the
      type IIa Na+/Pi cotransporter: II. Substrate interaction and voltage dependency
      of two functionally important sites.
AB  - Functionally important sites in the predicted first and fourth extracellular
      linkers of the type IIa Na+/Pi cotransporter (NaPi-IIa) were identified by
      cysteine scanning mutagenesis (Ehnes et al., 2004). Cysteine substitution or
      modification with impermeant and permeant methanethiosulfonate (MTS) reagents at
      certain sites resulted in changes to the steady-state voltage dependency of the
      cotransport mode (1 mM Pi, 100 mM Na+ at pH 7.4) of the mutants. At Gly-134 (ECL
      1) and Met-533 (ECL-4), complementary behavior of the voltage dependency was
      documented with respect to the effect of cys-substitution and modification. G134C
      had a weak voltage dependency that became even stronger than that of the wild
      type (WT) after MTS incubation. M533C showed a WT-like voltage dependency that
      became markedly weaker after MTS incubation. To elucidate the underlying
      mechanism, the steady-state and presteady-state kinetics of these mutants were
      studied in detail. The apparent affinity constants for Pi and Na+ did not show
      large changes after MTS exposure. However, the dependency on external protons was
      changed in a complementary manner for each mutant. This suggested that cys
      substitution at Gly-134 or modification of Cys-533 had induced similar
      conformational changes to alter the proton modulation of transport kinetics. The
      changes in steady-state voltage dependency correlated with changes in the
      kinetics of presteady-state charge movements determined in the absence of Pi,
      which suggested that voltage-dependent transitions in the transport cycle were
      altered. The steady-state and presteady-state behavior was simulated using an
      eight-state kinetic model in which the transition rate constants of the empty
      carrier and translocation of the fully loaded carrier were found to be critical
      determinants of the transport kinetics. The simulations predict that cys
      substitution at Gly-134 or cys modification of Cys-533 alters the preferred
      orientation of the empty carrier from an inward to outward-facing conformation
      for hyperpolarizing voltages.

PMID- 15504900
TI  - Long term endocrine regulation of nucleoside transporters in rat intestinal
      epithelial cells.
AB  - We studied the regulation of nucleoside transporters in intestinal epithelial
      cells upon exposure to either differentiating or proliferative agents. Rat
      intestinal epithelial cells (line IEC-6) were incubated in the presence of
      differentiating (glucocorticoids) or proliferative (EGF and TGF-alpha) agents.
      Nucleoside uptake rates and nucleoside transporter protein and mRNA levels were
      assessed. The signal transduction pathways used by the proliferative stimuli were
      analyzed. We found that glucocorticoids induce an increase in sodium-dependent,
      concentrative nucleoside transport rates and in protein and mRNA levels of both
      rCNT2 and rCNT1, with negligible effects on the equilibrative transporters. EGF
      and TGF-alpha induce an increase in the equilibrative transport rate, mostly
      accounted for by an increase in rENT1 activity and mRNA levels, rENT2 mRNA levels
      remaining unaltered. This effect is mimicked by another proliferative stimulus
      that functions as an in vitro model of epithelial wounding. Here, rENT1 activity
      and mRNA levels are also increased, although the signal transduction pathways
      used by the two stimuli are different. We concluded that differentiation of rat
      intestinal epithelial cells is accompanied by increased mature enterocyte
      features, such as concentrative nucleoside transport (located at the brush border
      membrane of the enterocyte), thus preparing the cell for its ultimate absorptive
      function. A proliferative stimulus induces the equilibrative nucleoside
      activities (mostly through ENT1) known to be located at the basolateral membrane,
      allowing the uptake of nucleosides from the bloodstream for the increased demands
      of the proliferating cell.

PMID- 15504901
TI  - Invariant aspartic Acid in muscle nicotinic receptor contributes selectively to
      the kinetics of agonist binding.
AB  - We examined functional contributions of interdomain contacts within the nicotinic
      receptor ligand binding site using single channel kinetic analyses, site-directed
      mutagenesis, and a homology model of the major extracellular region. At the
      principal face of the binding site, the invariant alphaD89 forms a highly
      conserved interdomain contact near alphaT148, alphaW149, and alphaT150. Patch
      clamp recordings show that the mutation alphaD89N markedly slows acetylcholine
      (ACh) binding to receptors in the resting closed state, but does not affect rates
      of channel opening and closing. Neither alphaT148L, alphaT150A, nor mutations at
      both positions substantially affects the kinetics of receptor activation, showing
      that hydroxyl side chains at these positions are not hydrogen bond donors for the
      strong acceptor alphaD89. However substituting a negative charge at alphaT148,
      but not at alphaT150, counteracts the effect of alphaD89N, demonstrating that a
      negative charge in the region of interdomain contact confers rapid association of
      ACh. Interpreted within the structural framework of ACh binding protein and a
      homology model of the receptor ligand binding site, these results implicate main
      chain amide groups in the domain harboring alphaW149 as principal hydrogen bond
      donors for alphaD89. The specific effect of alphaD89N on ACh association suggests
      that interdomain hydrogen bonding positions alphaW149 for optimal interaction
      with ACh.

PMID- 15504903
TI  - Polyvalent cations constitute the voltage gating particle in human connexin37
      hemichannels.
AB  - Connexins oligomerize to form intercellular channels that gate in response to
      voltage and chemical agents such as divalent cations. Historically, these are
      believed to be two independent processes. Here, data for human connexin37 (hCx37)
      hemichannels indicate that voltage gating can be explained as block/unblock
      without the necessity for an independent voltage gate. hCx37 hemichannels closed
      at negative potentials and opened in a time-dependent fashion at positive
      potentials. In the absence of polyvalent cations, however, the channels were open
      at relatively negative potentials, passing current linearly with respect to
      voltage. Current at negative potentials could be inhibited in a concentration
      dependent manner by the addition of polyvalent cations to the bathing solution.
      Inhibition could be explained as voltage-dependent block of hCx37, with the field
      acting directly on polyvalent cations, driving them through the pore to an
      intracellular site. At positive potentials, in the presence of polyvalent
      cations, the field favored polyvalent efflux from the intracellular blocking
      site, allowing current flow. The rate of appearance of current depended on the
      species and valence of the polyvalent cation in the bathing solution. The rate of
      current decay upon repolarization depended on the concentration of polyvalent
      cations in the bathing solution, consistent with deactivation by polyvalent
      block, and was rapid (time constants of tens of milliseconds), implying a high
      local concentration of polyvalents in or near the channel pore. Sustained
      depolarization slowed deactivation in a flux-dependent, voltage- and time
      independent fashion. The model for hCx37 voltage gating as polyvalent
      block/unblock can be expanded to account for observations in the literature
      regarding hCx37 gap junction channel behavior.

PMID- 15504902
TI  - Developmental regulation of calcium-dependent feedback in Xenopus rods.
AB  - The kinetics of activation and inactivation in the phototransduction pathway of
      developing Xenopus rods were studied. The gain of the activation steps in
      transduction (amplification) increased and photoresponses became more rapid as
      the rods matured from the larval to the adult stage. The time to peak was
      significantly shorter in adults (1.3 s) than tadpoles (2 s). Moreover, adult rods
      recovered twice as fast from saturating flashes than did larval rods without
      changes of the dominant time constant (2.5 s). Guanylate cyclase (GC) activity,
      determined using IBMX steps, increased in adult rods from approximately 1.1 s(-1)
      to 3.7 s(-1) 5 s after a saturating flash delivering 6,000 photoisomerizations.
      In larval rods, it increased from 1.8 s(-1) to 4.0 s(-1) 9 s after an equivalent
      flash. However, the ratio of amplification to the measured dark phosphodiesterase
      activity was constant. Guanylate cyclase-activating protein (GCAP1) levels and
      normalized Na+/Ca2+, K+ exchanger currents were increased in adults compared with
      tadpoles. Together, these results are consistent with the acceleration of the
      recovery phase in adult rods via developmental regulation of calcium homeostasis.
      Despite these large changes, the single photon response amplitude was
      approximately 0.6 pA throughout development. Reduction of calcium feedback with
      BAPTA increased adult single photon response amplitudes threefold and reduced its
      cutoff frequency to that observed with tadpole rods. Linear mathematical modeling
      suggests that calcium-dependent feedback can account for the observed differences
      in the power spectra of larval and adult rods. We conclude that larval Xenopus
      maximize sensitivity at the expense of slower response kinetics while adults
      maximize response kinetics at the expense of sensitivity.

PMID- 15504904
TI  - Altered inactivation of Ca2+ current and Ca2+ release in mouse muscle fibers
      deficient in the DHP receptor gamma1 subunit.
AB  - Functional impacts of the skeletal muscle-specific Ca2+ channel subunit gamma1
      have previously been studied using coexpression with the cardiac alpha1C
      polypeptide in nonmuscle cells and primary-cultured myotubes of gamma1-deficient
      mice. Data from single adult muscle fibers of gamma-/- mice are not yet
      available. In the present study, we performed voltage clamp experiments on
      enzymatically isolated mature muscle fibers of the m. interosseus obtained from
      gamma+/+ and gamma-/- mice. We measured L-type Ca2+ inward currents and
      intracellular Ca2+ transients during 100-ms step depolarizations from a holding
      potential of -80 mV. Ratiometric Ca2+ transients were analyzed with a removal
      model fit approach to calculate the flux of Ca2+ from the sarcoplasmic reticulum.
      Ca2+ current density, Ca2+ release flux, and the voltage dependence of activation
      of both Ca2+ current and Ca2+ release were not significantly different. By
      varying the holding potential and recording Ca2+ current and Ca2+ release flux
      induced by 100-ms test depolarizations to +20 mV, we studied quasi-steady-state
      properties of slow voltage-dependent inactivation. For the Ca2+ current, these
      experiments showed a right-shifted voltage dependence of inactivation.
      Importantly, we could demonstrate that a very similar shift occurred also in the
      inactivation curve of Ca2+ release. Voltages of half maximal inactivation were
      altered by 16 (current) and 14 mV (release), respectively. Muscle fiber bundles,
      activated by elevated potassium concentration (120 mM), developed about threefold
      larger contracture force in gamma-/- compared with gamma+/+. This difference was
      independent of the presence of extracellular Ca2+ and likely results from the
      lower sensitivity to voltage-dependent inactivation of Ca2+ release. These
      results demonstrate a specific alteration of voltage-dependent inactivation of
      both Ca2+ entry and Ca2+ release by the gamma1 subunit of the dihydropyridine
      receptor in mature muscle fibers of the mouse.

PMID- 15504905
TI  - Cell differentiation: reciprocal regulation of Apaf-1 and the inhibitor of
      apoptosis proteins.
AB  - The molecular mechanisms by which differentiated cells combat cell death and
      injury have remained unclear. In the current issue, it has been shown in neurons
      that cell differentiation is accompanied by a decrease in Apaf-1 and the activity
      of the apoptosome with an increased ability of the inhibitor of apoptosis
      proteins (IAPs) to sustain survival (Wright et al., 2004). These results,
      together with earlier ones, deepen our understanding of how cell death and the
      apoptosome are regulated during differentiation and in tumor cells.

PMID- 15504906
TI  - Getting the message across, STAT! Design principles of a molecular signaling
      circuit.
AB  - The STAT transcription factors, usually referred to as "latent cytoplasmic
      proteins," have experienced a fundamental reevaluation of their dynamic
      properties. This review focuses on recent studies that have identified continuous
      transport factor-independent nucleocytoplasmic cycling of STAT1, STAT3, and STAT5
      as a basic principle of cytokine signaling. In addition, molecular mechanisms
      that modulate flux rates or cause retention were recognized, and together these
      findings have provided novel insight into the rules of cellular signal
      processing.

PMID- 15504907
TI  - Coordinating cytoskeletal tracks to polarize cellular movements.
AB  - For many years after the discovery of actin filaments and microtubules, it was
      widely assumed that their polymerization, organization, and functions were
      largely distinct. However, in recent years it has become increasingly apparent
      that coordinated interactions between microtubules and filamentous actin are
      involved in many polarized processes, including cell shape, mitotic spindle
      orientation, motility, growth cone guidance, and wound healing. In the past few
      years, significant strides have been made in unraveling the intricacies that
      govern these intertwined cytoskeletal rearrangements.

PMID- 15504908
TI  - The critical role of cyclin D2 in adult neurogenesis.
AB  - Adult neurogenesis (i.e., proliferation and differentiation of neuronal
      precursors in the adult brain) is responsible for adding new neurons in the
      dentate gyrus of the hippocampus and in the olfactory bulb. We describe herein
      that adult mice mutated in the cell cycle regulatory gene Ccnd2, encoding cyclin
      D2, lack newly born neurons in both of these brain structures. In contrast,
      genetic ablation of cyclin D1 does not affect adult neurogenesis. Furthermore, we
      show that cyclin D2 is the only D-type cyclin (out of D1, D2, and D3) expressed
      in dividing cells derived from neuronal precursors present in the adult
      hippocampus. In contrast, all three cyclin D mRNAs are present in the cultures
      derived from 5-day-old hippocampi, when developmental neurogenesis in the dentate
      gyrus takes place. Thus, our results reveal the existence of molecular mechanisms
      discriminating adult versus developmental neurogeneses.

PMID- 15504909
TI  - Endothelial barrier disruption by VEGF-mediated Src activity potentiates tumor
      cell extravasation and metastasis.
AB  - VEGF is unique among angiogenic growth factors because it disrupts endothelial
      barrier function. Therefore, we considered whether this property of VEGF might
      contribute to tumor cell extravasation and metastasis. To test this, mice lacking
      the Src family kinases Src or Yes, which maintain endothelial barrier function in
      the presence of VEGF, were injected intravenously with VEGF-expressing tumor
      cells. We found a dramatic reduction in tumor cell extravasation in lungs or
      livers of mice lacking Src or Yes. At the molecular level, VEGF compromises the
      endothelial barrier by disrupting a VE-cadherin-beta-catenin complex in lung
      endothelium from wild-type, but not Yes-deficient, mice. Disrupting the
      endothelial barrier directly with anti-VE-cadherin both amplifies metastasis in
      normal mice and overcomes the genetic resistance in Yes-deficient mice.
      Pharmacological blockade of VEGF, VEGFR-2, or Src stabilizes endothelial barrier
      function and suppresses tumor cell extravasation in vivo. Therefore, disrupting
      Src signaling preserves host endothelial barrier function providing a novel host
      targeted approach to control metastatic disease.

PMID- 15504910
TI  - The 4q subtelomere harboring the FSHD locus is specifically anchored with
      peripheral heterochromatin unlike most human telomeres.
AB  - This paper investigates the nuclear localization of human telomeres and,
      specifically, the 4q35 subtelomere mutated in facioscapulohumeral dystrophy
      (FSHD). FSHD is a common muscular dystrophy that has been linked to contraction
      of D4Z4 tandem repeats, widely postulated to affect distant gene expression. Most
      human telomeres, such as 17q and 17p, avoid the nuclear periphery to reside
      within the internal, euchromatic compartment. In contrast, 4q35 localizes at the
      peripheral heterochromatin with 4p more internal, generating a reproducible
      chromosome orientation that we relate to gene expression profiles. Studies of
      hybrid and translocation cell lines indicate this localization is inherent to the
      distal tip of 4q. Investigation of heterozygous FSHD myoblasts demonstrated no
      significant displacement of the mutant allele from the nuclear periphery.
      However, consistent association of the pathogenic D4Z4 locus with the
      heterochromatic compartment supports a potential role in regulating the
      heterochromatic state and makes a telomere positioning effect more likely.
      Furthermore, D4Z4 repeats on other chromosomes also frequently organize with the
      heterochromatic compartment at the nuclear or nucleolar periphery, demonstrating
      a commonality among chromosomes harboring this subtelomere repeat family.

PMID- 15504911
TI  - The GTPase Arf1p and the ER to Golgi cargo receptor Erv14p cooperate to recruit
      the golgin Rud3p to the cis-Golgi.
AB  - Rud3p is a coiled-coil protein of the yeast cis-Golgi. We find that Rud3p is
      localized to the Golgi via a COOH-terminal domain that is distantly related to
      the GRIP domain that recruits several coiled-coil proteins to the trans-Golgi by
      binding the small Arf-like GTPase Arl1p. In contrast, Rud3p binds to the GTPase
      Arf1p via this COOH-terminal "GRIP-related Arf-binding" (GRAB) domain. Deletion
      of RUD3 is lethal in the absence of the Golgi GTPase Ypt6p, and a screen of other
      mutants showing a similar genetic interaction revealed that Golgi targeting of
      Rud3p also requires Erv14p, a cargo receptor that cycles between the endoplasmic
      reticulum and Golgi. The one human protein with a GRAB domain, GMAP-210
      (CEV14/Trip11/Trip230), is known to be on the cis-Golgi, but the COOH-terminal
      region that contains the GRAB domain has been reported to bind to centrosomes and
      gamma-tubulin (Rios, R.M, A. Sanchis, A.M. Tassin, C. Fedriani, and M. Bornens.
      2004. Cell. 118:323-335). In contrast, we find that this region binds to the
      Golgi in a GRAB domain-dependent manner, suggesting that GMAP-210 may not link
      the Golgi to gamma-tubulin and centrosomes.

PMID- 15504912
TI  - Decreased apoptosome activity with neuronal differentiation sets the threshold
      for strict IAP regulation of apoptosis.
AB  - Despite the potential of the inhibitor of apoptosis proteins (IAPs) to block
      cytochrome c-dependent caspase activation, the critical function of IAPs in
      regulating mammalian apoptosis remains unclear. We report that the ability of
      endogenous IAPs to effectively regulate caspase activation depends on the
      differentiation state of the cell. Despite being expressed at equivalent levels,
      endogenous IAPs afforded no protection against cytochrome c-induced apoptosis in
      naive pheochromocytoma (PC12) cells, but were remarkably effective in doing so in
      neuronally differentiated cells. Neuronal differentiation was also accompanied
      with a marked reduction in Apaf-1, resulting in a significant decrease in
      apoptosome activity. Importantly, this decrease in Apaf-1 protein was directly
      linked to the increased ability of IAPs to stringently regulate apoptosis in
      neuronally differentiated PC12 and primary cells. These data illustrate
      specifically how the apoptotic pathway acquires increased regulation with
      cellular differentiation, and are the first to show that IAP function and
      apoptosome activity are coupled in cells.

PMID- 15504913
TI  - UCS protein Rng3p activates actin filament gliding by fission yeast myosin-II.
AB  - We purified native Myo2p/Cdc4p/Rlc1p (Myo2), the myosin-II motor required for
      cytokinesis by Schizosaccharomyces pombe. The Myo2p heavy chain associates with
      two light chains, Cdc4p and Rlc1p. Although crude Myo2 supported gliding motility
      of actin filaments in vitro, purified Myo2 lacked this activity in spite of
      retaining full Ca-ATPase activity and partial actin-activated Mg-ATPase activity.
      Unc45-/Cro1p-/She4p-related (UCS) protein Rng3p restored the full motility and
      actin-activated Mg-ATPase activity of purified Myo2. The COOH-terminal UCS domain
      of Rng3p alone restored motility to pure Myo2. Thus, Rng3p contributes directly
      to the motility activity of native Myo2. Consistent with a role in Myo2
      activation, Rng3p colocalizes with Myo2p in the cytokinetic contractile ring. The
      absence of Rlc1p or mutations in the Myo2p head or Rng3p compromise the in vitro
      motility of Myo2 and explain the defects in cytokinesis associated with some of
      these mutations. In contrast, Myo2 with certain temperature-sensitive forms of
      Cdc4p has normal motility, so these mutations compromise other functions of Cdc4p
      required for cytokinesis.

PMID- 15504914
TI  - Roles of p-ERM and Rho-ROCK signaling in lymphocyte polarity and uropod
      formation.
AB  - Front-rear asymmetry in motile cells is crucial for efficient directional
      movement. The uropod in migrating lymphocytes is a posterior protrusion in which
      several proteins, including CD44 and ezrin/radixin/moesin (ERM), are
      concentrated. In EL4.G8 T-lymphoma cells, Thr567 phosphorylation in the COOH
      terminal domain of ezrin regulates the selective localization of ezrin in the
      uropod. Overexpression of the phosphorylation-mimetic T567D ezrin enhances uropod
      size and cell migration. T567D ezrin also induces construction of the CD44
      associated polar cap, which covers the posterior cytoplasm in staurosporine
      treated, uropod-disrupted EL4.G8 cells or in naturally unpolarized X63.653
      myeloma cells in an actin cytoskeleton-dependent manner. Rho-associated coiled
      coil-containing protein kinase (ROCK) inhibitor Y-27632 disrupts the uropod but
      not the polar cap, indicating that Rho-ROCK signaling is required for posterior
      protrusion but not for ERM phosphorylation. Phosphorylated ezrin associates with
      Dbl through its NH2-terminal domain and causes Rho activation. Moreover,
      constitutively active Q63L RhoA is selectively localized in the rear part of the
      cells. Thus, phosphorylated ERM has a potential function in establishing plasma
      membrane "posteriority" in the induction of the uropod in T lymphocytes.

PMID- 15504915
TI  - Integrins direct Src family kinases to regulate distinct phases of
      oligodendrocyte development.
AB  - Specific integrins expressed on oligodendrocytes, the myelin-forming cells of the
      central nervous system, promote either differentiation and survival or
      proliferation by amplification of growth factor signaling. Here, we report that
      the Src family kinases (SFKs) Fyn and Lyn regulate each of these distinct
      integrin-driven behaviors. Fyn associates with alpha6beta1 and is required to
      amplify platelet-derived growth factor survival signaling, to promote myelin
      membrane formation, and to switch neuregulin signaling from a
      phosphatidylinositol 3-kinase to a mitogen-activated protein kinase pathway
      (thereby changing the response from proliferation to differentiation). However,
      earlier in the lineage Lyn, not Fyn, is required to drive alphaVbeta3-dependent
      progenitor proliferation. The two SFKs respond to integrin ligation by different
      mechanisms: Lyn, by increased autophosphorylation of a catalytic tyrosine; and
      Fyn, by reduced Csk phosphorylation of the inhibitory COOH-terminal tyrosine.
      These findings illustrate how different SFKs can act as effectors for specific
      cell responses during development within a single cell lineage, and, furthermore,
      provide a molecular mechanism to explain similar region-specific hypomyelination
      in laminin- and Fyn-deficient mice.

PMID- 15504916
TI  - A transmigratory cup in leukocyte diapedesis both through individual vascular
      endothelial cells and between them.
AB  - The basic route and mechanisms for leukocyte migration across the endothelium
      remain poorly defined. We provide definitive evidence for transcellular (i.e.,
      through individual endothelial cells) diapedesis in vitro and demonstrate that
      virtually all, both para- and transcellular, diapedesis occurs in the context of
      a novel "cuplike" transmigratory structure. This endothelial structure was
      comprised of highly intercellular adhesion molecule-1- and vascular cell adhesion
      molecule-1-enriched vertical microvilli-like projections that surrounded
      transmigrating leukocytes and drove redistribution of their integrins into linear
      tracks oriented parallel to the direction of diapedesis. Disruption of
      projections was highly correlated with inhibition of transmigration. These
      findings suggest a novel mechanism, the "transmigratory cup", by which the
      endothelium provides directional guidance to leukocytes for extravasation.

PMID- 15504917
TI  - Cancer outcomes research and the arenas of application.

PMID- 15504918
TI  - Descriptive review of the literature on breast cancer outcomes: 1990 through
      2000.
AB  - BACKGROUND: There is increasing interest in the incorporation of nonbiomedical
      outcomes into cancer research. OBJECTIVE: Our goal was to review the use of
      nonbiomedical outcomes in research on breast cancer care. DATA SOURCES: We
      conducted a MEDLINE search of all studies on breast cancer quality of life,
      preferences, satisfaction, and economics that were published during the period
      from January 1, 1990, through December 31, 2000. We also searched bibliographies
      of published articles. STUDY SELECTION: We included original primary research and
      excluded reviews, methods papers, studies conducted outside the United States and
      Western Europe, or studies with fewer than 100 subjects. DATA ABSTRACTION: Data
      were abstracted by using a structured tool. DATA SYNTHESIS: There were 1089
      articles identified; 230 were included. The greatest proportion of research
      focused on survivorship followed by screening. The most frequently reported
      outcomes were health-related quality of life (54%) followed by economic analyses
      (38%) and patient satisfaction (14%); only 9% measured patient preferences. Few
      studies included more than 10% nonwhite populations or focused on the elderly. No
      single instrument was used in more than 10% of the studies, and many authors
      developed de novo tools for use in their study. Methodologic flaws were prevalent
      and included use of nonstandard economic methods, insufficient power, low or
      differential response rates, and lack of control for baseline status. CONCLUSION:
      At present, outcomes measurement is variable in its approach and application to
      breast cancer care. More research is needed to develop practical approaches that
      are reliable, valid, and feasible in routine practice, that are applicable to
      diverse populations, and that can inform interventions to improve the quality of
      care across the full spectrum of services.

PMID- 15504919
TI  - Colorectal cancer screening and treatment: review of outcomes research.
AB  - BACKGROUND: Colorectal cancer is the second leading cause of cancer deaths in the
      United States each year. Screening is effective in reducing colorectal cancer
      mortality; however, compliance with screening is poor, and factors associated
      with its compliance are poorly understood. The outcomes of treatment of
      colorectal cancer (surgery, radiation therapy, and chemotherapy) may have
      profound effects on quality of life (QOL). Furthermore, colorectal cancer
      screening and treatment may be expensive, and the costs are important from a
      policy perspective. This review examines patient-centered outcomes research
      related to colorectal cancer screening and treatment and outlines the work that
      has been done in several areas, including patient preferences, QOL, and economic
      analysis. METHODS: The literature on the health outcomes associated with
      colorectal cancer screening and treatment was reviewed. A MEDLINE search of
      English language articles published from January 1, 1990 through February 2001,
      was conducted and was supplemented by a review of references of obtained
      articles. Criteria for study inclusion were identified a priori. A standardized
      data abstraction form was developed. Summary statistical analyses were performed
      on the results. RESULTS: Six hundred eighty-six articles were selected for
      review. In total, 530 articles were excluded because they either did not include
      patient-centered outcomes, were duplicate articles, or could not be obtained.
      There were 156 articles included in the analysis; 67 addressed screening, 18
      examined surveillance of high-risk groups, 22 concerned treatment of local
      disease, 10 examined treatment of local and metastatic disease, and 19 considered
      treatment of metastatic disease only. One study examined end-of-life care. In 19
      studies, the phase of care was unspecified. CONCLUSIONS: Standardized, disease
      specific QOL instruments should be applied in clinical trials so that the results
      may be compared across different types of interventions. Valid and reliable
      methods that accurately capture patient preferences regarding screening and
      treatment should be developed.

PMID- 15504920
TI  - Outcomes research in lung cancer.
AB  - BACKGROUND: Lung cancer is the leading cause of cancer death in the United
      States. Most therapeutic interventions for this disease achieve modest benefits,
      but at the expense of nontrivial toxicity and cost, making it an important area
      for outcomes analysis. OBJECTIVE: The goal of the study was to audit the
      literature of outcomes pertaining to lung cancer. DATA SOURCES: The English
      language outcomes literature published during the period from 1990 through 2000
      was systematically reviewed and analyzed. STUDY SELECTION: Papers had to contain
      original research in one of the following areas: quality of life, health
      economics, communication, decision making, quality of care, or patient
      satisfaction. DATA EXTRACTION: The literature was reviewed and analyzed by the
      author. DATA SYNTHESIS: The lung cancer outcomes literature is growing rapidly.
      Of the 199 studies examined, 106 (53%) dealt primarily with quality-of-life
      measurement, 69 (35%) examined costs, 11 (6%) dealt with communication and
      decision making, 11 (6%) assessed the quality of care, and two (1%) evaluated
      patient satisfaction. Most studies focused on the palliative phase of care.
      Women, the elderly, and minorities were generally well represented in these
      studies. The European Organization for Research and Treatment of Cancer QLQ-C30
      with its LC13 module is emerging as the most commonly employed quality-of-life
      instrument in lung cancer studies. Economic studies vary widely in their quality.
      The literature is relatively sparse with respect to quality of care,
      communication, and decision making, however. CONCLUSIONS: A substantial body of
      outcomes research has been published since 1990. Further work is needed in the
      area of methods development, in the assessment of the impact of new technologies,
      and in the monitoring of the quality of lung cancer care in vulnerable
      populations.

PMID- 15504921
TI  - Health-related quality of life, satisfaction, and economic outcome measures in
      studies of prostate cancer screening and treatment, 1990-2000.
AB  - Prostate cancer outcomes research incorporates a broad spectrum of endpoints,
      from clinical or intermediate endpoints, such as tumor shrinkage or patient
      compliance, to final endpoints, such as survival or disease-free survival. Three
      types of nontraditional endpoints that are of growing interest-health-related
      quality of life (QOL), satisfaction with care, and economic cost impact-hold the
      promise of improving our ability to understand the full burden of prostate cancer
      screening and treatment. In this article we review the last decade's published
      literature regarding the health-related QOL, satisfaction, and economic outcomes
      of prostate cancer screening and treatment to determine the "state of the
      science" of outcomes measurement. The focus is the enumeration of the types of
      outcome measurement used in the studies not the determination of the results of
      the studies. Studies were identified by searching Medline (1990-2000). Articles
      were included if they presented original data on any patient-centered outcome
      (including costs or survival alone) for men screened and treated for prostate
      cancer. Review papers were excluded unless they were quantitative syntheses of
      the results of other primary studies. Economic and decision analytic papers were
      included if they presented information on outcomes of real or hypothetical
      patient cohorts. Each retrieved article was reviewed by one of the authors.
      Included papers were assigned one primary, mutually exclusive study design. For
      the "primary data" studies, information was abstracted on care setting, dates of
      the study, sample size, racial distribution, age, tumor differentiation, tumor
      stage, survival, statistical power, and types of outcomes measures (QOL-generic,
      QOL-cancer specific, QOL-prostate cancer specific, satisfaction, costs,
      utilities, and other). For the "economic and decision analytic" papers,
      information was abstracted on stage of disease, age range, outcomes, costs, and
      whether utilities were measured. Of the 198 included papers, there were 161
      primary data papers categorized as follows: randomized trial (n = 28),
      nonrandomized trial (n = 13), prospective or retrospective cohort study (n = 55),
      case-control study (n = 0), cross-sectional study (n = 63), and meta-analysis (n
      = 2). The remaining 37 papers were economic and decision analytic papers. Among
      the 149 primary data papers that contained patient outcome data, there were 42
      standard instruments used, accounting for 44% (179 of 410) of the measures
      overall. Almost three-quarters (71%) of papers included one, two, or three
      outcomes measures of all types (standard and nonstandard); three papers included
      seven outcomes measures, and one paper included nine. Over the 11-year time
      period, there was a nonstatistically significant trend toward more frequent use
      of standardized QOL instruments and a statistically significant trend toward
      increased reporting of race (P = .003). Standardization of measurement of health
      related QOL, satisfaction with care, and economic cost effect among men screened
      and treated for prostate cancer is needed. A core set of similar questions, both
      generic and disease-specific, should ideally be asked in every study, although
      investigators should be encouraged to include additional question sets as
      appropriate to individual studies to get a more complete picture of how patients
      screened and treated for this condition are doing over time.

PMID- 15504922
TI  - A structured review of studies on health-related quality of life and economic
      evaluation in pediatric acute lymphoblastic leukemia.
AB  - BACKGROUND: A comprehensive review was made of the literature on the health
      related quality of life (HRQL) and economic outcomes of children with acute
      lymphoblastic leukemia (ALL), the most common of all cancers in childhood.
      OBJECTIVES: The primary objectives of the review were to locate and describe
      measures of HRQL used in pediatrics and in pediatric oncology that might be
      applicable to ALL, to summarize studies that have applied HRQL measures to ALL,
      to identify and summarize economic evaluations of the costs and consequences of
      care for pediatric ALL, and to identify areas requiring further research. DATA
      SOURCES: To identify the HRQL literature in pediatric ALL, searches were run on
      the major biomedical and social science bibliographic databases. Search terms
      included a variety of MeSH and other thesaurus terms, text words, names of HRQL
      instruments, and the names of key authors in the field. The economic literature
      searches included most of the same databases, with the addition of the National
      Health Service Economic Evaluation Database and EconLit. Searches on specific
      authors and instruments and hand searches were also conducted. STUDY SELECTION:
      Only English language studies published from 1975 through 2000 were included.
      DATA EXTRACTION: Standardized data extraction forms were used to abstract
      information from HRQL and economic evaluation studies. Two reviewers
      independently screened the search results, and differences were resolved by
      consensus. DATA SYNTHESIS: A number of generic HRQL measures, both adult and
      pediatric, have been applied in pediatric ALL. In addition, a number of pediatric
      oncology-specific instruments and pediatric oncology disease-specific instruments
      have been developed. Most of these instruments have been used to measure the
      health status of patients undergoing therapy. Despite the limited numbers of
      patients and resources available to assess HRQL measures in children with cancer,
      a fairly substantial body of literature has been published. Economic studies of
      pediatric ALL have only recently been undertaken. Most studies focus on a
      particular, narrow aspect of costs associated with the disease. There are
      relatively few cost-effectiveness studies that compare the costs and consequences
      of two or more treatment options. There are no published, comprehensive economic
      evaluations of pediatric ALL. CONCLUSIONS: HRQL measures provide not only
      important information on the improvements offered by new therapies but also an
      outcome measure for economic evaluations. Recently developed HRQL measures and
      applications that include the direct assessments of children are important
      contributions. By the age of 7 or 8 years, children can generally provide
      reliable responses. Furthermore, children often provide information that is not
      available from parental reports (e.g., in the more subjective areas of pain and
      emotion). However, the use of multiple viewpoints, such as the patient, parent,
      and health professional perspectives, can provide valid and important
      complementary information. Expertise in HRQL measurement should be included in
      the design of most future trials. Funds for HRQL research should be made
      available to enhance the scope of HRQL activities by organizations such as the
      Children's Oncology Group. In the near future, further work to generate evidence
      of validity for available HRQL measures for use in children with ALL will be a
      high priority. Continuation of inquiries into the methods for HRQL assessment of
      younger children (i.e., preschoolers) is also a priority.

PMID- 15504923
TI  - Assessing cancer-related quality of life across a spectrum of applications.
AB  - Health-related quality of life (HRQOL) is increasingly assessed to understand the
      effects of cancer and cancer-related interventions. At the macro level,
      monitoring HRQOL in the population and in cancer survivors may be important to
      track progress against cancer and evaluate the outcome of policies and programs.
      At the meso level, where most research, to date, has been focused, HRQOL data may
      be used in descriptive and analytic studies to understand the impact of cancer,
      patterns of care, and effects of interventions for cancer prevention, treatment,
      and continuing care. At the micro level, HRQOL data can inform individual patient
      and clinician decision making. Current data show that validated and commonly used
      HRQOL questionnaires are not interchangeable. Consequently, in determining which
      HRQOL measures are most appropriate for a given application, it is especially
      important to carefully consider both the study hypotheses and patient population.
      Future progress at all levels requires better understanding of the meaning and
      interpretation of HRQOL scores.

PMID- 15504924
TI  - Measuring economic outcomes of cancer.
AB  - Economic outcomes are increasingly important in cancer research. This article
      provides an introduction to the nature and measurement of economic outcomes in
      cancer and gives the reader entry points to a considerable literature on
      measuring economic endpoints in health and medicine. Economic outcomes data are
      defined here as measures of resources consumed in prevention, detection, and
      treatment of cancer and its sequellae. Part I of this essay discusses the
      questions addressed by economic outcomes. Part II presents a typology of and
      introduction to measurement of economic outcomes. Part III discusses important
      measurement issues and calls for development and validation of standardized
      protocols and questionnaires to measure economic outcomes, especially at the
      patient level.

PMID- 15504925
TI  - Use of cancer performance measures in population health: a macro-level
      perspective.
AB  - The use of performance measurement to inform macro-level studies of cancer
      control and quality of care is receiving increasing interest at the state,
      national, and international level. This article describes the use of these
      measures to inform health policy and monitor cancer disparities and disease
      burden. Applications are discussed in clinical and provider-reported outcomes
      such as cancer incidence, mortality and survival, and outcome-linked processes of
      care, and patient-reported outcomes such as health-related quality of life and
      patient satisfaction/experience with care. The use of economic measures to
      monitor and evaluate the burden of illness is also discussed. The growing demand
      for surveillance capability coupled with the need to expand both the quality and
      breadth of available measure sets, suggests that there is a need to supplement
      traditional clinical and provider-reported process and outcomes measures with
      patient-reported outcomes measures such as health-related quality of life and
      patient satisfaction and experience with care. In addition, there is also a need
      to broaden and standardize outcome-linked process-of-care measures to improve the
      ability to measure and monitor incremental progress in improving cancer care.
      Finally, better measures of indirect costs of cancer care, such as loss
      productivity and caregiver burden among the aged, would improve national
      estimates of the cost of illness associated with cancer.

PMID- 15504926
TI  - Taking stock of health-related quality-of-life measurement in oncology practice
      in the United States.
AB  - This article focuses on the routine use of patient-reported outcomes measures in
      oncology clinical practice to monitor patient progress and inform decision
      making; and in particular, on measuring patient-reported health-related quality
      of life (HRQOL). The article summarizes the current literature on the
      acceptability to patients and clinicians of HRQOL measurement and on the
      effectiveness of feedback to clinicians about their patients' concerns and
      quality of life. It also describes the experiences recounted by clinicians and
      researchers who have been implementing such efforts and concludes that in the
      United States, little HRQOL measurement occurs in oncology practice. That is,
      much methodological development has occurred, but many challenges to its
      widespread adoption exist. These challenges include limitations in knowledge
      about how to apply outcomes instruments, and clinician, patient-related, and
      health system issues. That effort deserves significant attention now. The way
      forward, however, does not lie simply in adding HRQOL measurement to other tasks
      that are part of everyday practice. Rather, attention to principles of effective
      dissemination and new information infrastructures and technologies, combined with
      redesign of care, should embed the routine use of patient-reported outcomes in
      the care process to provide timely response to patients' needs for information
      and services.

PMID- 15504927
TI  - A health outcomes framework for assessing health status and quality of life:
      enhanced data for decision making.
AB  - BACKGROUND: Currently, information to improve health status and quality of life
      is derived from independently designed data systems that range from population
      based health surveys to health records used in managing individual patient care.
      But there is no coherent strategy for using these data sources in concert across
      diverse applications. Thus, it is frequently difficult to compare or combine
      results across studies to provide population-level inferences based on findings
      from specific subpopulations. OBJECTIVE: The Health Outcomes Framework is an
      analytic structure to provide more comprehensive information about the health
      status and quality-of-life impact of disease and its treatment. This framework
      consists of three components: (1) a core set of health, lifestyle, and economic
      questionnaires that collect data from an individual's perspective; (2)
      applications that range from population to patient care levels; and (3) time.
      Although health is the outcome of interest, lifestyle behaviors and economic and
      political factors are important determinants of health, which also need to be
      studied using standardized procedures; thus, they are included in the core. This
      article focuses on the nature and application of a core health status and quality
      of-life instrument. To be useful across a range of applications, such a core
      instrument needs to have three conceptual characteristics: (1) a theoretical
      model that regards health as a continuum of states; (2) domains that represent
      policy-relevant aspects of impairment, disability, and handicap; and (3) a set of
      societal preferences for these domains. In addition, the core needs to address
      three practical concerns: (1) brevity, (2) methods of administration that are
      suitable for respondents with diverse capabilities, and (3) documentation that is
      publicly available. These features are discussed using examples from currently
      available, multi-domain generic instruments, each of which has some, but not all,
      of the necessary features of the core instrument. CONCLUSION: The Health Outcomes
      Framework is intended to be a cooperative effort. It is proposed that the
      National Cancer Institute and the Centers for Disease Control and Prevention take
      leadership roles not only by adopting a core health status and quality-of-life
      instrument for use in current and future cancer data collection activities but
      also in encouraging industry and academic investigators to implement this core
      instrument in their cancer studies. Having a vertically integrated core
      instrument can lead to more representative data for informing decision making and
      ultimately for obtaining a more equitable distribution of health.

PMID- 15504928
TI  - Cancer outcomes research.

PMID- 15504929
TI  - Overview: obesity: what does it have to do with kidney disease?

PMID- 15504930
TI  - The metabolic syndrome as a risk factor for chronic kidney disease: more than a
      fat chance?

PMID- 15504931
TI  - Obesity-initiated metabolic syndrome and the kidney: a recipe for chronic kidney
      disease?

PMID- 15504932
TI  - The inflammatory syndrome: the role of adipose tissue cytokines in metabolic
      disorders linked to obesity.
AB  - The metabolic effects of obesity have made this highly prevalent disease one of
      the most common risk factors for diabetes, hypertension, and atherosclerosis, the
      leading causes of end-stage renal failure. However, obesity per se, as defined by
      body mass index, is less predictive of the development of these diseases than is
      the presence of a constellation of obesity-related abnormalities now known as the
      metabolic syndrome. Recognition of this syndrome, which can readily be identified
      in clinical settings using defined threshold values for waist circumference, BP,
      fasting glucose, and dyslipidemia, allows for earlier intervention in these high
      risk patients. Systemic insulin resistance has been implicated as one possible
      factor that links visceral obesity to adverse metabolic consequences; however,
      the mechanism whereby adipose tissue causes alterations in insulin sensitivity
      remains unclear. Infection and inflammation are commonly associated with insulin
      resistance, and visceral obesity is associated with a chronic, low-grade
      inflammatory state, suggesting that inflammation may be a potential mechanism
      whereby obesity leads to insulin resistance. Moreover, adipose tissue is now
      recognized as an immune organ that secretes numerous immunomodulatory factors and
      seems to be a significant source of inflammatory signals known to cause insulin
      resistance. Therefore, inflammation within white adipose tissue may be a crucial
      step contributing to the emergence of many of the pathologic features that
      characterize the metabolic syndrome and result in diabetes and atherosclerosis.
      This review describes the role of proinflammatory cytokines and hormones released
      by adipose tissue in generating the chronic inflammatory profile associated with
      visceral obesity.

PMID- 15504933
TI  - Peroxisome proliferator-activated receptor family and its relationship to renal
      complications of the metabolic syndrome.
AB  - Peroxisome proliferator-activated receptors (PPAR) are members of the nuclear
      hormone receptor superfamily of ligand-activated transcription factors. Three
      PPAR isoforms, designated PPARalpha, -beta/delta, and -gamma, have been
      identified and attracted enormous attention as a result of the key role that
      these receptors play in regulating adipogenesis, lipid metabolism, insulin
      sensitivity, inflammation, and BP. Growing evidence points to a causative
      relationship between PPAR activity and the metabolic syndrome, including insulin
      resistance, glucose intolerance or type 2 diabetes, obesity, dyslipidemia,
      hypertension, atherosclerosis, and albuminuria. Importantly, both PPAR-alpha
      activators, such as the fibric acid class of hypolipidemic drugs, and PPAR-gamma
      agonists, including antidiabetic thiazolidinediones, have been proved to be
      effective for improving diverse aspects of the metabolic syndrome. All three PPAR
      isoforms seem to play important roles in the development of diabetic nephropathy
      in type 2 diabetes. Accumulating data suggesting that PPAR may serve as potential
      therapeutic targets for treating the metabolic syndrome and its related renal
      complications have begun to emerge. This article reviews the literature
      pertaining to the action, ligand selectivity, and physiologic role of PPAR.
      Particular emphasis is placed on their pathogenic roles in the metabolic syndrome
      and the therapeutic utility of PPAR modulators in the treatment of diabetic
      nephropathy.

PMID- 15504934
TI  - The relationship between hyperinsulinemia, hypertension and progressive renal
      disease.
AB  - The incidence of end-stage renal disease (ESRD) has risen dramatically in the
      past decade, mainly due to the increasing prevalence of diabetes mellitus, and
      both impaired glucose tolerance and hypertension are important contributors to
      rising rates of ESRD. Obesity, especially the visceral type, is associated with
      peripheral resistance to insulin actions and hyperinsulinemia, which predisposes
      to development of diabetes. A common genetic predisposition to insulin resistance
      and hypertension and the coexistence of these two disorders predisposes to
      premature atherosclerosis. A constellation of metabolic and cardiovascular
      derangements, which also includes dyslipidemia, dysglycemia, endothelial
      dysfunction, fibrinolytic and inflammatory abnormalities, left ventricular
      hypertrophy, microalbuminuria, and increased oxidative stress, is referred to as
      the cardiometabolic syndrome. The components of this syndrome, individually and
      interdependently, substantially increase the risk of renal disease,
      cardiovascular disease (CVD) and mortality. Similar findings and cardiorenal risk
      factors can occur in subjects with android obesity without excess body
      weight.Recently, microalbuminuria has been gaining momentum as a component and
      marker for the cardiometabolic syndrome, in addition to being an early marker for
      progressive renal disease in patients with this syndrome or in those with
      diabetes. Furthermore, it is now established as an independent predictor of CVD
      and CVD mortality. This review examines the relationship between insulin
      resistance/hyperinsulinemia and hypertension in the context of cardiometabolic
      syndrome, progressive renal disease and accelerated CVD. The importance of
      microalbuminuria as an early marker for the cardiometabolic syndrome is also
      discussed in this review.

PMID- 15504935
TI  - Contribution of multidrug resistance protein 2 (MRP2/ABCC2) to the renal
      excretion of p-aminohippurate (PAH) and identification of MRP4 (ABCC4) as a novel
      PAH transporter.
AB  - p-Aminohippurate (PAH) is the classical substrate used in the characterization of
      organic anion transport in renal proximal tubular cells. Although basolateral
      transporters for PAH uptake from blood into the cell have been well
      characterized, there is still little knowledge on the apical urinary efflux
      transporters. The multidrug resistance protein 2 (MRP2/ABCC2) is localized to the
      apical membrane and mediates ATP-dependent PAH transport, but its contribution to
      urinary PAH excretion is not known. In this report, we show that renal excretion
      of PAH in isolated perfused kidneys from wild-type and Mrp2-deficient (TR(-))
      rats is not significantly different. Uptake of [(14)C]PAH in membrane vesicles
      expressing two different MRP2 clones isolated from Sf9 and MDCKII cells exhibited
      a low affinity for PAH (Sf9, 5 +/- 2 mM; MDCKII, 2.1 +/- 0.6 mM). Human MRP4
      (ABCC4), which has recently been localized to the apical membrane, expressed in
      Sf9 cells had a much higher affinity for PAH (K(m) = 160 +/- 50 microM). Various
      inhibitors of MRP2-mediated PAH transport also inhibited MRP4. Probenecid
      stimulated MRP2 at low concentrations but had no effect on MRP4; but at high
      probenecid concentrations, both MRP2 and MRP4 were inhibited. Sulfinpyrazone only
      stimulated MRP2, but inhibited MRP4. Real-time PCR and Western blot analysis
      showed that renal cortical expression of MRP4 is approximately fivefold higher as
      compared with MRP2. MRP4 is a novel PAH transporter that has higher affinity for
      PAH and is expressed more highly in kidney than MRP2, and may therefore be more
      important in renal PAH excretion.

PMID- 15504936
TI  - Antidiuretic effect of hydrochlorothiazide in lithium-induced nephrogenic
      diabetes insipidus is associated with upregulation of aquaporin-2, Na-Cl co
      transporter, and epithelial sodium channel.
AB  - Thiazides have been used in patients with nephrogenic diabetes insipidus (NDI) to
      decrease urine volume, but the mechanism by which it produces the paradoxic
      antidiuretic effect remains unclear. Previous studies have reported that
      downregulation of aquaporin-2 (AQP2) is important for the development of lithium
      induced (Li-induced) polyuria and that hydrochlorothiazide (HCTZ) increases renal
      papillary osmolality and Na(+) concentration in Brattleboro rats. For elucidating
      the molecular basis of the antidiuretic action of HCTZ in diabetes insipidus,
      whether administration of HCTZ may affect the expression of AQP2 and major renal
      Na(+) transporters in Li-induced NDI rats was investigated, using
      semiquantitative immunoblotting and immunohistochemistry. After feeding male
      Sprague-Dawley rats Li chloride-containing rat diet for 4 wk, HCTZ or vehicle was
      infused subcutaneously via osmotic minipump. Urine output was significantly
      decreased by HCTZ treatment, whereas it was not changed in vehicle-treated rats.
      Urine osmolality was also higher in HCTZ-treated rats than in vehicle-treated
      rats. Semiquantitative immunoblotting using whole-kidney homogenates revealed
      that HCTZ treatment caused a significant partial recovery in AQP2 abundance from
      Li-induced downregulation. AQP2 immunohistochemistry showed compatible findings
      with the immunoblot results in both cortex and medulla. The abundances of
      thiazide-sensitive NaCl co-transporter and alpha-epithelial sodium channel were
      increased by HCTZ treatment. Notably, HCTZ treatment induced a shift in molecular
      weight of gamma-epithelial sodium channel from 85 to 70 kD, consistent with
      previously demonstrated aldosterone stimulation. The upregulation of AQP2 and
      distal renal Na(+) transporters in response to HCTZ treatment may account for the
      antidiuretic action of HCTZ in NDI.

PMID- 15504937
TI  - Mechanisms of mitogen-activated protein kinase inhibition by parathyroid hormone
      in osteoblast-like cells.
AB  - Parathyroid hormone (PTH) dose dependently inhibits growth factor- and stress
      induced osteoblast proliferation via inactivating mitogen-activated protein
      kinase (MAPK) signaling pathways. Osteoblasts have recently been shown to express
      MAPK phosphatase (MKP)-1, a dual-specific phosphatase inactivator of MAPK.
      Investigated was the role of MKPs in the PTH-induced attenuation of MAPK and Jun
      N-terminal kinase (JNK) signaling in osteoblast-like UMR106-01 cells. PTH induced
      a persistent inhibition of p42/44 MAPK and JNK phosphorylation starting at 10 min
      of incubation and lasting for at least 2 h. Actinomycin D affected both p42/44
      MAPK and JNK dephosphorylation by PTH, suggesting a transcription-dependent
      mechanism of action. PTH rapidly and transiently induced expression of MKP-1. MKP
      1 mRNA was already elevated after 10 min of 10(-7) M PTH incubation, reached
      maximal expression after 30 to 60 min, and remained elevated after 4 h. MKP-1
      protein was also upregulated within 30 to 60 min of PTH administration. The
      protein kinase A inhibitor H89 partly reduced PTH-induced MKP-1 expression, but
      the protein kinase C inhibitor bisindolylmaleimide had no effect, suggesting that
      PTH induces MKP-1 mainly via the protein kinase A pathway. MKP-2 mRNA was
      downregulated after 2 h after an early period of induction, and MKP-3 mRNA was
      immediately reduced. Ro 318-220 did not affect PTH-induced MAPK inactivation but
      effectively blocked JNK dephosphorylation. The time course of PTH-induced MKP-1
      protein expression closely correlated with JNK dephosphorylation. PTH attenuates
      the stress-induced JNK signaling pathway in osteoblasts via induction of MKP-1
      synthesis but inhibits the p42/44 MAPK pathway mainly via transcription
      independent mechanisms.

PMID- 15504938
TI  - WT1 activates a glomerular-specific enhancer identified from the human nephrin
      gene.
AB  - The glomerular filtration barrier separates the blood from the urinary space.
      Nephrin is a transmembrane protein that belongs to the immunoglobulin superfamily
      and is localized to the slit diaphragms that are a critical component of this
      filtration barrier. Mutations in the nephrin gene (NPHS1) lead to congenital
      Finnish nephropathy, whereas alterations in the level of nephrin expression have
      been identified in a wide range of acquired glomerular diseases. A 186-bp
      fragment from the human NPHS1 promoter is capable of directing podocyte-specific
      expression of a beta-galactosidase transgene when placed in front of a
      heterologous minimal promoter in transgenic mice. The Wilms tumor suppressor gene
      (WT1) is a zinc-finger-containing transcription factor that is coexpressed with
      NPHS1 in differentiated podocytes; gel shift binding assays demonstrate that a
      recombinant WT1 protein can bind and activate the 186-bp NPHS1 fragment in a
      sequence-specific manner. Taken together, these results suggest that WT1 may be
      required for regulation of the NPHS1 gene in vivo.

PMID- 15504939
TI  - Human vascular smooth muscle cells undergo vesicle-mediated calcification in
      response to changes in extracellular calcium and phosphate concentrations: a
      potential mechanism for accelerated vascular calcification in ESRD.
AB  - Patients with ESRD have a high circulating calcium (Ca) x phosphate (P) product
      and develop extensive vascular calcification that may contribute to their high
      cardiovascular morbidity. However, the cellular mechanisms underlying vascular
      calcification in this context are poorly understood. In an in vitro model,
      elevated Ca or P induced human vascular smooth muscle cell (VSMC) calcification
      independently and synergistically, a process that was potently inhibited by
      serum. Calcification was initiated by release from living VSMC of membrane-bound
      matrix vesicles (MV) and also by apoptotic bodies from dying cells. Vesicles
      released by VSMC after prolonged exposure to Ca and P contained preformed basic
      calcium phosphate and calcified extensively. However, vesicles released in the
      presence of serum did not contain basic calcium phosphate, co-purified with the
      mineralization inhibitor fetuin-A and calcified minimally. Importantly, MV
      released under normal physiologic conditions did not calcify, and VSMC were also
      able to inhibit the spontaneous precipitation of Ca and P in solution. The potent
      mineralization inhibitor matrix Gla protein was found to be present in MV, and
      pretreatment of VSMC with warfarin markedly enhanced vesicle calcification. These
      data suggest that in the context of raised Ca and P, vascular calcification is a
      modifiable, cell-mediated process regulated by vesicle release. These vesicles
      contain mineralization inhibitors derived from VSMC and serum, and perturbation
      of the production or function of these inhibitors would lead to accelerated
      vascular calcification.

PMID- 15504940
TI  - Hepatocyte growth factor ameliorates renal interstitial inflammation in rat
      remnant kidney by modulating tubular expression of macrophage chemoattractant
      protein-1 and RANTES.
AB  - Hepatocyte growth factor (HGF) has been shown to reduce renal injury in a variety
      of animal models of chronic renal disease. Suggested mechanisms to explain this
      action include prevention of tubular cell apoptosis, blocking epithelial-to
      mesenchymal transition, and promotion of extracellular matrix degradation.
      Inflammation is another common finding in kidneys that progress to end-stage
      renal failure; however, the effect of HGF on inflammation has hardly been
      investigated. For examining this issue, beginning 2 wk after subtotal
      nephrectomy, rats received a continuous infusion of recombinant HGF,
      neutralization of endogenous HGF by daily injection of an anti-HGF antibody, or
      preimmune IgG for an additional 2 wk. HGF infusion halted the progression of
      proteinuria and decreased renal collagen accumulation. Renal inflammation in both
      glomeruli and tubulointerstitium was significantly attenuated, associated with
      reductions in the tubular expression of the chemokines macrophage chemoattractant
      protein-1 (MCP-1) and RANTES (regulated upon expression normal T cell expressed
      and secreted). In contrast, HGF neutralization worsened renal fibrosis,
      aggravated renal inflammation, and enhanced tubular expression of MCP-1 and
      RANTES. In vitro, HGF suppressed basal and TNF-alpha-induced expression of these
      chemokines at both the mRNA and protein levels in a time- and dose-dependent
      manner in proximal tubular epithelial cells. HGF also blunted TNF-alpha-induced
      nuclear translocation and activation of NF-kappaB, a pivotal transcription factor
      that regulates chemokine expression. Immunohistochemistry showed that activated
      NF-kappaB was evident in tubules in remnant kidneys and increased remarkably with
      anti-HGF treatment. HGF infusion markedly suppressed expression of activated NF
      kappaB in remnant kidneys. These findings suggest that the beneficial effect of
      HGF in chronic renal disease is attributable, at least in part, to a direct anti
      inflammatory action, likely via NF-kappaB, on tubular epithelial cells.

PMID- 15504941
TI  - A synthetic heparanase inhibitor reduces proteinuria in passive Heymann
      nephritis.
AB  - The beta-D-endoglycosidase heparanase has been proposed to be important in the
      pathogenesis of proteinuria by acting to selectively degrade the negatively
      charged side chains of heparan sulfate proteoglycans (HSPG) within the glomerular
      basement membrane (GBM). A loss of the negatively charged HSPG may result in
      alteration of the permselective properties of the GBM, loss of glomerular
      epithelial and endothelial cell anchor points, and liberation of growth factors.
      This study examined the effect of PI-88, a sulfated oligosaccharide heparanase
      inhibitor, on renal function, glomerular ultrastructure, and proteinuria.
      Continuous PI-88 infusion at 25 mg/kg per d did not adversely affect animal
      behavior, growth, or GFR. Cortical tubular vacuolation, however, was observed by
      light microscopy, and GBM thickness was significantly reduced in these animals (P
      < 0.0002). Tissue distribution studies using [(35)S]-labeled PI-88 revealed high
      levels of radioactivity in the kidney after a single subcutaneous injection of 25
      mg/kg, suggesting protracted accumulation; moreover, active PI-88 was detected in
      urine. In passive Heymann nephritis, PI-88 delivered as a continuous infusion at
      25 mg/kg per d significantly reduced autologous-phase proteinuria, at day 14 (P <
      0.009), in the absence of altered sheep antibody deposition, C5b-9 deposition,
      and circulating rat anti-sheep antibody titers. Glomerular vascular endothelial
      growth factor and fibroblast growth factor expression was unaffected by PI-88
      administration. However, PI-88 administration significantly prevented glomerular
      HSPG loss as demonstrated by quantitative immunofluorescence studies (P < 0.0001)
      in the absence of altered agrin distribution. These data therefore confirm the
      importance of heparanase in the development of proteinuria.

PMID- 15504942
TI  - Selectin inhibitor bimosiamose prolongs survival of kidney allografts by
      reduction in intragraft production of cytokines and chemokines.
AB  - Binding of the P-, L-, and E-selectins to sialyl Lewis(x) (sLe(x)) retards
      circulating leukocytes, thereby facilitating their attachment to the blood
      vessels of allografts. Whether the selectin inhibitor bimosiamose (BIMO;
      C(46)H(54)O(16) . 0.25 H(2)O [867.4 molecular weight]) inhibits the rejection
      process of kidney allografts in a rat model was examined. Rat recipients acutely
      rejected kidney allografts at a mean survival time of 8.8 +/- 0.75 d. An
      intravenous 7-d infusion by osmotic pump of 2.5, 5, 10, or 20 mg/kg BIMO extended
      kidney allograft survival to 11.5 +/- 2.2 d (P < 0.03), 25.4 +/- 11.4 d (P <
      0.006), 37.4 +/- 13.6 d (P < 0.001), and 39.8 +/- 34.5 d (P < 0.01),
      respectively. Combination of BIMO with cyclosporine produced synergistic
      interactions, as documented by the combination index (CI) values of 0.34 to 0.43
      (CI <1 is synergistic; CI = 1 is additive; and CI >1 is antagonistic). Similarly,
      BIMO interacted synergistically with sirolimus (CI = 0.64) and FTY720 (CI =
      0.22). While the mechanism of immunosuppression was being analyzed, decreased
      infiltration of CD4(+), CD8(+), and macrophages on day 7 after grafting was
      observed. Multiple cytokines were also expressed, including IL-1alpha, IL-1beta,
      IL-2, IL-4, IL-6, IL-10, IL-12, IL-18, TNF-alpha, and IFN-gamma in kidney
      allografts on days 3, 5, and 7 after grafting, as measured by a ribonuclease
      protection assay. Furthermore, at similar time points, BIMO treatment reduced
      intragraft expression of P-selectin glycoprotein ligand-1, CX(3)CL1, CCL19,
      CCL20, and CCL2. Thus, BIMO blocks allograft rejection by reduction of intragraft
      expression of cytokines and chemokines.

PMID- 15504943
TI  - Moxonidine normalizes sympathetic hyperactivity in patients with eprosartan
      treated chronic renal failure.
AB  - Enalapril and losartan reduce but not normalize sympathetic hyperactivity in
      patients with hypertensive chronic renal failure (CRF). This study assessed the
      effect of chronic eprosartan on BP and sympathetic activity, and assessed the
      effect of moxonidine during chronic eprosartan treatment. In 11 stable patients
      with CRF (creatinine clearance 47 +/- 10 ml/min), muscle sympathetic nerve
      activity (MSNA; peroneal nerve), BP, and baroreceptor sensitivity were measured
      in the absence of antihypertensive drugs (except diuretics) during chronic
      eprosartan therapy (600 mg for 6 wk) and in 9 patients after moxonidine (0.2 mg
      for 6 wk) was added. Normovolemia was controlled by diuretics and confirmed by
      extracellular fluid volume measurements. BP, heart rate, and MSNA were higher in
      patients than in 22 controls. During eprosartan therapy, mean arterial pressure
      (111 +/- 9 to 98 +/- 7 mmHg, P < 0.001), heart rate (71 +/- 10 to 65 +/- 8 bpm, P
      < 0.001), and MSNA (35 +/- 10 to 27 +/- 8 bursts/min, P < 0.001) decreased. After
      the addition of moxonidine (n = 9), a further reduction of mean arterial pressure
      to 89 +/- 7 mmHg (P < 0.05) and of MSNA to 20 +/- 10 bursts/min (P < 0.05)
      occurred. Sympathetic activity in patients with CRF can be normalized, and
      angiotensin II-independent sympathetic hyperactivity contributes to the
      pathogenesis of renal hypertension. Sympathetic hyperactivity is associated with
      poor cardiovascular outcomes, implying that reduction might be beneficial to the
      patients. The addition of moxonidine to angiotensin II antagonist treatment might
      be appropriate.

PMID- 15504944
TI  - Association of chronic kidney disease and anemia with physical capacity: the
      heart and soul study.
AB  - Chronic kidney disease (CKD) and anemia are common conditions in the outpatient
      setting, but their independent and additive effects on physical capacity have not
      been well characterized. The association of CKD and anemia with self-reported
      physical function was evaluated and exercise capacity was measured in patients
      with coronary disease. A cross-sectional study of 954 outpatients enrolled in the
      Heart and Soul study was performed. CKD was defined as a measured creatinine
      clearance <60 ml/min, and anemia was defined as a hemoglobin level of <12g/dl.
      Physical function was self-assessed using the physical limitation subscale of the
      Seattle Angina Questionnaire (0 to 100), and exercise capacity was defined as
      metabolic equivalent tasks achieved at peak exercise. In unadjusted analyses, CKD
      was associated with lower self-reported physical function (67.6 versus 74.9; P <
      0.001) and lower exercise capacity (5.5 versus 7.9; P < 0.001). Similarly, anemia
      was associated with lower self-reported physical function (62.6 versus 74.3; P <
      0.001) and exercise capacity (5.7 versus 7.5; P < 0.001). After multivariate
      adjustment, CKD (69.4 versus 74.2; P = 0.003) and anemia (67.5 versus 73.6; P =
      0.009) each remained associated with lower mean self-reported physical function.
      In addition, patients with CKD (6.3 versus 7.7; P < 0.001) or anemia (6.5 versus
      7.4; P = 0.004) had lower adjusted mean exercise capacities. Participants with
      both CKD and anemia had lower self-reported physical function and exercise
      capacity than those with either alone. CKD and anemia are independently
      associated with physical limitation and reduced exercise capacity in outpatients
      with coronary disease, and these effects are additive. The broad impact of these
      disease conditions merits further study.

PMID- 15504945
TI  - Effect of an increase in C-reactive protein level during a hemodialysis session
      on mortality.
AB  - The prevalence of chronic inflammation is high in dialysis patients. Moreover, it
      is associated with an increased mortality risk, yet the origin of chronic
      inflammation in dialysis patients remains unclear. The aim of this study was to
      determine the effect of a hemodialysis session (HD) on C-reactive protein (CRP)
      levels and to study the relation with survival. As part of a large, prospective,
      multicenter study in the Netherlands (Netherlands Cooperative Study on the
      Adequacy of Dialysis), patients who were started on dialysis treatment between
      September 1997 and May 1999 were included. Demographic data, clinical data, and
      serum samples were collected at regularly timed intervals. From this cohort, a
      random sample of patients was taken. CRP levels were determined before and after
      an HD session and before the next session. Date of death or censoring was
      recorded until September 2002. A total of 186 HD patients were included. Mean age
      was 65 yr (SD, 13); 56% were male. A total of 71 patients had a CRP level below
      the detection limit (3 mg/L), 68 patients showed no increase in CRP during an HD
      session (no-increase group), and 47 (25%) patients showed an increase in CRP
      level during an HD session (increase-group). No statistically difference in mean
      CRP levels before the dialysis session was found between the increase group (22.3
      mg/L) and the no-increase group (19.4 mg/L). In the subsequent interdialytic
      period, CRP levels returned to the levels of the initial CRP value. Two-year
      survival was 44% in the increase group and 66% in the no-increase group (P =
      0.09). Independent of CRP level before the session and adjusted for age,
      comorbidity, nutritional status, and primary kidney disease, a raise of 1 mg/L
      CRP during a session was associated with a 9% increased mortality risk (adjusted
      hazard ratio, 1.09; 95% CI, 1.02 to 1.16). The present study showed an increase
      in CRP level during a single dialysis session in 25% of the patients; during the
      succeeding interdialytic period, CRP level returned to its original value. More
      important, however, an increase in CRP level during an HD session was
      independently associated with a higher mortality risk.

PMID- 15504946
TI  - Racial and center differences in hemodialysis adequacy in children treated at
      pediatric centers: a North American Pediatric Renal Transplant Cooperative Study
      (NAPRTCS) report.
AB  - This study assessed hemodialysis adequacy in pediatric centers. Monthly adequacy
      data were requested in NAPRTCS enrollees on hemodialysis for at least 6 mo. Data
      forms were returned for 147 children from 32 centers. Data are presented for the
      138 children (57% boys, 45% black) that were dialyzed 3 times/wk, representing
      2282 patient-months of follow-up. Pre- and postdialysis BUN levels were reported
      in all children. Kt/V values were reported in 76 children; however, sufficient
      data were obtained to calculate Kt/V in 129 children. On average, 14.9 Kt/V and
      15.2 urea reduction ratio (URR) values were calculated per child. Aggregate
      dialysis dose was defined as adequate if Kt/V was >1.2 in at least 75% of
      calculated Kt/V measures within a subject. Mean +/- SD age was 11.3 +/- 3.7 yr
      (median, 12.0 yr). Hemodialysis dose was variable within subjects (median CV%:
      URR 8.2, Kt/V 16.9). Aggregate dialysis dose was adequate in 70% of subjects.
      Multivariate logistic regression showed male gender (OR, 0.41; 95% CI, 0.16 to
      0.98), black race (OR, 0.28; 95% CI, 0.11 to 0.67), larger body surface area
      (fourth versus first quartile: OR, 0.22; 95% CI, 0.05 to 0.80), and absence of
      reported Kt/V at the treating center (OR, 0.26; 95% CI, 0.10 to 0.62) were
      significant predictors of inadequate dialysis dose. Age, renal diagnosis, and
      center size were not associated with adequacy. Racial and gender disparities in
      hemodialysis dose existed among children at specialized academic pediatric
      centers and a substantial proportion received inadequate hemodialysis.

PMID- 15504947
TI  - Increased resting energy expenditure in hemodialysis patients with severe
      hyperparathyroidism.
AB  - Several metabolic derangements, including enhanced protein catabolism, have been
      suggested to be associated with increased circulating parathyroid hormone (PTH)
      in patients with secondary hyperparathyroidism (HPT). Such conditions, therefore,
      might lead to an increase in energy expenditure. The present study examined by
      indirect calorimetry the resting energy expenditure (REE) of 15 hemodialysis
      patients who have severe HPT (PTH = 1457 +/- 676 pg/ml) and were pair-matched for
      age and gender to 15 hemodialysis patients with mild to moderate HPT (PTH = 247
      +/- 196 pg/ml). Both groups were also pair-matched for age and gender to a group
      of 15 healthy adult subjects (control). In six patients from the severe HPT group
      submitted to total parathyroidectomy, REE was determined 6 mo after the surgery.
      The groups were not different regarding lean body mass (LBM) measured by
      bioelectric impedance, serum C-reactive protein, and bicarbonate. Thyroid
      stimulating hormone was within the normal range in all groups. Nonadjusted REE
      was significantly higher in the severe HPT group (1674 +/- 337 kcal/d) compared
      with patients with mild to moderate HPT (1388 +/- 229 kcal/d; P < 0.05). Both
      groups did not differ from the control group (1468 +/- 323 kcal/d). When
      adjustment of REE for LBM was performed using the multiple regression analysis,
      patients with mild to moderate HPT and control subjects had significantly lower
      REE (-231 and -262 kcal, respectively) than that of the severe HPT group.
      Considering all patients together, nonadjusted REE correlated directly with LBM
      (r = 0.61; P < 0.01). PTH correlated strongly with LBM in the severe HPT group (r
      = -0.82; P < 0.01). In the multiple linear regression analysis, only LBM and PTH
      were independent determinants of REE (n = 30; R(2) = 0.47). REE decreased
      significantly in the six patients who were evaluated 6 mo after parathyroidectomy
      (from 1617 +/- 339 to 1226 +/- 253; P = 0.02). These results demonstrate that
      hemodialysis patients with severe HPT have increased REE that might be reduced
      after parathyroidectomy.

PMID- 15504948
TI  - Peritoneal transport characteristics with glucose polymer-based dialysis fluid in
      children.
AB  - Scarce data are available on the use of glucose polymer-based dialysate in
      children. The effects of glucose polymer-based dialysate on peritoneal fluid
      kinetics and solute transport were studied in pediatric patients who were on
      chronic peritoneal dialysis, and a comparison was made with previously published
      results in adult patients. In nine children, two peritoneal equilibration tests
      were performed using 3.86% glucose and 7.5% icodextrin as a test solution.
      Dextran 70 was added as a volume marker to calculate fluid kinetics. Serum and
      dialysate samples were taken for determination of urea, creatinine, and sodium.
      After calculation of the initial transcapillary ultrafiltration (TCUF) rate, it
      was possible to calculate the contribution of aquaporin-mediated (AQP-mediated)
      water transport to ultrafiltration for icodextrin and 3.86% glucose and the part
      of L(p)S (the product of the peritoneal surface area and the hydraulic
      permeability) caused by AQP. In children, the transport parameters were similar
      for the two solutions, except for TCUF, which was lower for icodextrin (0.9
      ml/min per 1.73 m(2)) as compared with 3.86% glucose (4 ml/min per 1.73 m(2)).
      Transport parameters were similar in children and adults for glucose, but with
      icodextrin, TCUF and marker clearance were significantly lower in children. AQP
      mediated water flow was 83 versus 50% with glucose (child versus adult; P < 0.01)
      and 18 versus 7% with icodextrin (P < 0.01). Data indicate that transport
      parameters in children using icodextrin are similar to glucose except for TCUF.
      Differences are explained by the absence of crystalloid osmosis and that TCUF was
      determined after a 4-h dwell. Comparison of transport parameters and peritoneal
      membrane characteristics between children and adults reveal that there seem to be
      differences in the amount and functionality of AQP. However, there are no
      differences in clinical efficacy of this transport pathway because the absolute
      flow through the AQP is identical in both groups using 3.86% glucose.

PMID- 15504949
TI  - Paradoxical antidiuretic effect of thiazides in diabetes insipidus: another piece
      in the puzzle.

PMID- 15504950
TI  - Inequality in quality: are patient health activation and CQI corrective
      approaches?

PMID- 15504951
TI  - Purinergic inhibition of the epithelial Na+ transport via hydrolysis of PIP2.
AB  - Stimulation of purinergic receptors inhibits amiloride-sensitive Na+ transport in
      epithelial tissues by an unknown mechanism. Because previous studies excluded the
      role of intracellular Ca2+ or protein kinase C, we examined whether purinergic
      regulation of Na+ absorption occurs via hydrolysis of phospholipid such as
      phosphatidylinositol-bisphosphates (PIP2). Inhibition of amiloride-sensitive
      short-circuit currents (Isc-Amil) by adenine 5'-triphosphate (ATP) in native
      tracheal epithelia and M1 collecting duct cells was suppressed by binding
      neomycin to PIP2, and recovery from ATP inhibition was abolished by blocking
      phosphatidylinositol-4-kinase or diacylglycerol kinase. Stimulation by ATP
      depleted PIP2 from apical membranes, and PIP2 co-immunoprecipitated the beta
      subunit of ENaC. ENaC was inhibited by ATP stimulation of P2Y2 receptors in
      Xenopus oocytes. Mutations in the PIP2 binding domain of betaENaC but not
      gammaENaC reduced ENaC currents without affecting surface expression.
      Collectively, these data supply evidence for a novel and physiologically relevant
      regulation of ENaC in epithelial tissues. Although surface expression is
      controlled by its C terminus, N-terminal binding of betaENaC to PIP2 determines
      channel activity.

PMID- 15504952
TI  - Molecular mechanisms of insulin resistance that impact cardiovascular biology.
AB  - Insulin resistance is concomitant with type 2 diabetes, obesity, hypertension,
      and other features of the metabolic syndrome. Because insulin resistance is
      associated with cardiovascular disease, both scientists and physicians have taken
      great interest in this disorder. Insulin resistance is associated with
      compensatory hyperinsulinemia, but individual contributions of either of these
      two conditions remain incompletely understood and a subject of intense
      investigation. One possibility is that in an attempt to overcome the inhibition
      within the metabolic insulin-signaling pathway, hyperinsulinemia may continue to
      stimulate the mitogenic insulin-signaling pathway, thus exerting its detrimental
      influence. Here we discuss some of the effects of insulin resistance and
      mechanisms of potentially detrimental influence of hyperinsulinemia in the
      presence of metabolic insulin resistance.

PMID- 15504953
TI  - Physiological hyperinsulinemia in dogs augments access of macromolecules to
      insulin-sensitive tissues.
AB  - Pharmacological doses of insulin increase limb blood flow and enhance tissue
      recruitment for small solutes such as glucose. We investigated whether elevating
      insulin within the physiological range (68 +/- 6 vs. 425 +/- 27 pmol/l) can
      influence tissue recruitment of [(14)C]inulin, an inert diffusionary marker of
      molecular weight similar to that of insulin itself. During hyperinsulinemic
      euglycemic clamps, transport parameters and distribution volumes of [(14)C]inulin
      were determined in conscious dogs by applying a three-compartment model to the
      plasma clearance data of intravenously injected [(14)C]inulin (0.8 microCi/kg).
      In a second set of experiments in anesthetized dogs with direct cannulation of
      the hindlimb skeletal muscle lymphatics, we measured a possible effect of
      physiological hyperinsulinemia on the response of the interstitial fluid of
      skeletal muscle to intravenously injected [(14)C]inulin and compared this
      response with the model prediction from plasma data. Physiological
      hyperinsulinemia caused a 48 +/- 10% (P < 0.005) and a 35 +/- 15% (P < 0.05)
      increase of peripheral and splanchnic interstitial distribution volumes for
      [(14)C]inulin. Hindlimb lymph measurements directly confirmed the ability of
      insulin to enhance the access of macromolecules to the peripheral interstitial
      fluid compartment. The present results show that physiological hyperinsulinemia
      will enhance the delivery of a substance of similar molecular size to insulin to
      previously less intensively perfused regions of insulin-sensitive tissues. Our
      data suggest that the delivery of insulin itself to insulin-sensitive tissues
      could be a mechanism of insulin action on cellular glucose uptake independent of
      and possibly synergistic with either enhanced blood flow distribution or GLUT4
      transporter recruitment to enhance glucose utilization. Because of the
      differences between inulin and insulin itself, whether delivery of the bioactive
      hormone is increased remains speculative.

PMID- 15504954
TI  - regulation of peroxisome proliferator-activated receptor-gamma activity by
      mammalian target of rapamycin and amino acids in adipogenesis.
AB  - Adipocyte differentiation is a developmental process that is critical for
      metabolic homeostasis and nutrient signaling. The mammalian target of rapamycin
      (mTOR) mediates nutrient signaling to regulate cell growth, proliferation, and
      diverse cellular differentiation. It has been reported that rapamycin, the
      inhibitor of mTOR and an immunosuppressant, blocks adipocyte differentiation, but
      the mechanism underlying this phenomenon remains unknown. Here we show that mTOR
      plays a critical role in 3T3-L1 preadipocyte differentiation and that mTOR kinase
      activity is required for this process. Rapamycin specifically disrupted the
      positive transcriptional feedback loop between CCAAT/enhancer-binding protein
      alpha and peroxisome proliferator-activated receptor-gamma (PPAR-gamma), two key
      transcription factors in adipogenesis, by directly targeting the transactivation
      activity of PPAR-gamma. In addition, we demonstrate for the first time that PPAR
      gamma activity is dependent on amino acid sufficiency, revealing a molecular link
      between nutrient status and adipogenesis. The results of our further
      investigation have led us to propose a model in which the mTOR pathway and the
      phosphatidylinositol 3-kinase/Akt pathway act in parallel to regulate PPAR-gamma
      activation during adipogenesis by mediating nutrient availability and insulin
      signals, respectively. It is interesting that troglitazone (a thiazolidinedione
      drug) reversed the inhibitory effects of rapamycin and amino acid deprivation,
      implicating therapeutic values of thiazolidinedione drugs to counter certain side
      effects of rapamycin as an immunosuppressant.

PMID- 15504955
TI  - CCAAT/enhancer binding protein and nuclear factor-Y regulate adiponectin gene
      expression in adipose tissue.
AB  - Adiponectin is one of the adipokines secreted by adipocytes and regulates energy
      homeostasis associated with insulin sensitivity, suggesting a possibility of
      nutritional regulation of adiponectin gene expression. In this study, we showed
      that the transcription of adiponectin gene was induced 4-6 h after refeeding of
      mice. Also, differentiated 3T3-L1 adipocytes that were treated with high glucose
      expressed significantly increased adiponectin mRNA. Promoter analysis using
      nuclear extracts from white adipose tissue revealed that CCAAT/enhancer binding
      protein (C/EBP) and nuclear factor-Y (NF-Y) bound on the -117/-73 region of the
      adiponectin promoter. This region was critical for the activity of the
      adiponectin promoter as the deletion or mutation of this region markedly
      diminished the promoter activity to a basal level. Furthermore, the C/EBP binding
      increased in both refed animal and high glucose-treated 3T3-L1 adipocytes in an
      electrophoretic mobility shift assay, suggesting that C/EBP is responsible for
      the dietary response of the adiponectin gene expression. Chromatin
      immunoprecipitation studies demonstrated the binding of C/EBP and NF-Y in both
      mouse and differentiated 3T3-L1 adipocytes and also that C/EBP binding increased
      in response to high glucose. These findings demonstrated that C/EBP and NF-Y are
      critical for the regulation of the adiponectin expression in response to
      nutrients and in the course of adipocyte differentiation.

PMID- 15504956
TI  - A new ATP-sensitive K+ channel-independent mechanism is involved in glucose
      excited neurons of mouse arcuate nucleus.
AB  - Glucose is known to modify electrical activity of neurons in different
      hypothalamic areas such as the arcuate nucleus (ARC) or the ventromedian nucleus.
      In these structures, it has been demonstrated that glucose-induced excitation of
      neurons involves ATP-sensitive K(+) (K(ATP)) channel closure. The aim of the
      present study was to determine whether ARC neurons were able to detect high
      extracellular glucose concentrations and which mechanisms were involved in this
      detection by using whole-cell and cell-attached patch-clamp techniques in acute
      mouse brain slices. An increase from 5 to 20 mmol/l glucose stimulated 19% and
      inhibited 9% of ARC neurons. Because of the high-glucose concentrations used, we
      called these neurons high-glucose-excited (HGE) and high-glucose-inhibited (HGI)
      neurons, respectively. Glucose-induced depolarization of HGE neurons was not
      abolished by tetrodotoxin treatment and was correlated with an increase of
      membrane conductance that reversed at approximately 20 mV. Experiments with
      diazoxide, pinacidil, or tolbutamide showed that K(ATP) channels were present and
      functional in most of the ARC neurons but were mostly closed at 5 mmol/l glucose.
      Moreover, HGE neurons were also present in ARC of Kir6.2 null mice. These results
      suggested that ARC neurons have the ability to sense higher glucose
      concentrations than 5 mmol/l through a new K(ATP) channel-independent mechanism.

PMID- 15504957
TI  - Platelet-derived growth factor stimulates glucose transport in skeletal muscles
      of transgenic mice specifically expressing platelet-derived growth factor
      receptor in the muscle, but it does not affect blood glucose levels.
AB  - Insulin stimulates the disposal of blood glucose into skeletal muscle and adipose
      tissues by the translocation of GLUT4 from intracellular pools to the plasma
      membrane, and consequently the concentration of blood glucose levels decreases
      rapidly in vivo. Phosphatidylinositol (PI) 3-kinase and Akt play a pivotal role
      in the stimulation of glucose transport by insulin, but detailed mechanisms are
      unknown. We and others reported that not only insulin but also platelet-derived
      growth factor (PDGF) and epidermal growth factor facilitate glucose uptake
      through GLUT4 translocation by activation of PI 3-kinase and Akt in cultured
      cells. However, opposite results were also reported. We generated transgenic mice
      that specifically express the PDGF receptor in skeletal muscle. In these mice,
      PDGF stimulated glucose transport into skeletal muscle in vitro and in vivo.
      Thus, PDGF apparently shares with insulin some of the signaling molecules needed
      for the stimulation of glucose transport. The degree of glucose uptake in vivo
      reached approximately 60% of that by insulin injection in skeletal muscle, but
      blood glucose levels were not decreased by PDGF in these mice. Therefore, PDGF
      induced disposal of blood glucose into skeletal muscle is insufficient for rapid
      decrease of blood glucose levels.

PMID- 15504958
TI  - Ciliary neurotrophic factorAx15 alters energy homeostasis, decreases body weight,
      and improves metabolic control in diet-induced obese and UCP1-DTA mice.
AB  - Ciliary neurotrophic factor (CNTF) potently reduces appetite and body weight in
      rodents and humans. We studied the short- and long-term effects of CNTF(Ax15), a
      second-generation CNTF analog, in diet-induced obese C57BL/6J mice and brown
      adipose tissue (BAT)-deficient obese UCP1-DTA (uncoupling protein 1-diphtheria
      toxin A) mice. CNTF(Ax15) administration (0.1, 0.3, or 1.0 microg . g(-1) . day(
      1) s.c.) for 3 or 7 days reduced food intake and body weight (mainly body fat
      mass). The effect of CNTF(Ax15) on food intake and body weight was more
      pronounced in CNTF(Ax15)-treated diet-induced obese C57BL/6J mice compared with
      pair-fed controls and was associated with suppressed expression of hypothalamic
      neuropeptide Y and agouti gene-related protein. Moreover, CNTF(Ax15) increased
      uncoupling protein 1 mRNA expression in BAT and energy expenditure in diet
      induced obese C57BL/6J mice. Longitudinal observations revealed a sustained
      reduction in body weight for several days post-CNTF(Ax15) treatment of CNTF(Ax15)
      treated but not pair-fed mice, followed by a gradual regain in body weight over
      28 days. Finally, CNTF(Ax15) administration improved the metabolic profile in
      both diet-induced obese C57BL/6J and UCP1-DTA mice and resulted in a
      significantly improved glycemic response to oral glucose tolerance tests in
      CNTF(Ax15)-treated UCP1-DTA compared with pair-fed mice of similar body weight.
      These data suggest that CNTF(Ax15) may act through a pathway downstream of the
      putative point responsible for leptin resistance in diet-induced obese C57BL/6J
      and UCP1-DTA mice to alter food intake, body weight, body composition, and
      metabolism. CNTF(Ax15) has delayed and persistent effects in diet-induced obese
      C57BL/6J mice, which account for a reduction in body weight over and above what
      would be expected based on decreased foot intake alone.

PMID- 15504959
TI  - Fas deficiency prevents type 1 diabetes by inducing hyporesponsiveness in islet
      beta-cell-reactive T-cells.
AB  - Type 1 diabetes is an autoimmune disease wherein autoreactive T-cells promote the
      specific destruction of pancreatic islet beta-cells. Evidence for a crucial role
      for Fas/FasL interactions in this destruction has been highly controversial
      because of the pleiotropic effects of Fas deficiency on the lymphoid and other
      systems. Fas-deficient mice are protected from spontaneous development of
      diabetes not because Fas has a role in the destruction of beta-cells, but rather
      because insulitis is abrogated. Fas may somehow be involved in the series of
      events provoking insulitis; for example, it may play a role in the physiological
      wave of beta-cell death believed to result in the export of pancreatic antigens
      to the pancreatic lymph nodes and, thereby, to circulating, naive, diabetogenic T
      cells for the first time. To explore the implication of Fas in these events, we
      crossed the lpr mutation into the BDC2.5 model of type 1 diabetes to make it
      easier to monitor direct effects on the pathogenic specificity. We demonstrated
      that BDC2.5/NOD(lpr/lpr) mice have qualitatively and quantitatively less
      aggressive insulitis than do BDC2.5/NOD mice. In vitro proliferation assays
      showed that BDC2.5/NOD(lpr/lpr) splenocytes proliferated less vigorously than
      those from control mice in the presence of islet extracts, which reflects their
      inability to produce interleukin-2, resulting in weaker pathogenicity.

PMID- 15504960
TI  - Activated protein C preserves functional islet mass after intraportal
      transplantation: a novel link between endothelial cell activation, thrombosis,
      inflammation, and islet cell death.
AB  - Clinical studies indicate that significant loss of functional islet mass occurs
      in the peritransplant period. Islets are injured as a result of detrimental
      effects of brain death, pancreas preservation, islet isolation, hypoxia,
      hyperglycemia, and immune-mediated events. In addition, recent studies
      demonstrated that islets are injured as a result of their exposure to blood and
      of activation of intrahepatic endothelial and Kupffer cells, resulting in
      inflammation and thrombosis. Activated protein C (APC) is an anticoagulant enzyme
      that also exerts anti-inflammatory and antiapoptotic activities by acting
      directly on cells. Here, we report that exogenous administration of recombinant
      murine APC (mAPC) significantly reduced loss of functional islet mass after
      intraportal transplantation in diabetic mice. Animals given mAPC exhibited better
      glucose control, higher glucose disposal rates, and higher arginine-stimulated
      acute insulin release. These effects were associated with reduced plasma
      proinsulin, intrahepatic fibrin deposition, and islet apoptosis early after the
      transplant. In vitro and in vivo data demonstrated that mAPC treatment was
      associated with a significant reduction of proinflammatory cytokine release after
      exposure of hepatic endothelial cells to islets. mAPC treatment also prevented
      endothelial cell activation and dysfunction elicited by intrahepatic embolization
      of isolated islets inherent to pancreatic islet transplantation (PIT). This study
      demonstrates multiple remarkable beneficial effects of mAPC for PIT and suggests
      that APC therapy may enhance the therapeutic efficacy of PIT in diabetic
      patients.

PMID- 15504961
TI  - Intracellular stress signaling pathways activated during human islet preparation
      and following acute cytokine exposure.
AB  - Pancreatic islet transplantation may successfully restore normoglycemia in type 1
      diabetic patients. However, successful grafting requires transplantation of a
      sufficient number of islets, usually requiring two or more donors. During the
      isolation process and following clinical transplantation, islets are subjected to
      severe adverse conditions that impair survival and ultimately contribute to graft
      failure. Here, we have mapped the major intracellular stress-signaling pathways
      that may mediate human islet loss during isolation and following cytokine attack.
      We found that the isolation procedure potently recruits two pathways consisting
      of |mitogen-activated protein kinase kinase (MKK)7 --> Jun NH(2)-terminal kinase
      (JNK)/p38 --> c-fos| and the |nuclear factor-kappaB (NF-kappaB) --> iNOS| module.
      Cytokines activate the |NF-kappaB --> iNOS| and |MKK4/MKK3/6 --> JNK/p38|
      pathways without recruitment of c-fos. Culturing the islets for 48 h after
      isolation allows for the activated pathways to return to background levels, with
      expression of MKK7 becoming undetectable. These data indicate that isolation and
      cytokines recruit different death pathways. Therefore, strategies might be
      rationally developed to avoid possible synergistic activation of these pathways
      in mediating islet loss during isolation and following grafting.

PMID- 15504962
TI  - Interplay of glucagon-like peptide-1 and transforming growth factor-beta
      signaling in insulin-positive differentiation of AR42J cells.
AB  - The differentiation of pancreatic exocrine AR42J cells into insulin-expressing
      endocrine cells has served as an important model for both endogenous in vivo beta
      cell differentiation as well as potential application to beta-cell engineering of
      progenitor cells. Exogenous activin, possibly working through intracellular smad
      2 and/or smad 3, as well as exogenous exendin-4 (a long-acting glucagon-like
      peptide-1 agonist) have both been shown to induce insulin-positive/endocrine
      differentiation in AR42J cells. In this study, we present evidence of significant
      interplay and interdependence of these two pathways as well as potential synergy
      between the pathways. In particular, insulin-positive differentiation seems to
      entail an exendin-4-induced drop in smad 2 and elevation in smad 3 in RNA levels.
      The latter appears to be dependent on endogenous transforming growth factor (TGF)
      beta isoform release by the AR42J cells and may serve as a mechanism to promote
      beta-cell maturation. The drop in smad 2 may mediate early endocrine commitment.
      The coapplication of exogenous exendin-4 and, specifically, low-dose exogenous
      TGF-beta1 led to a dramatic 20-fold increase in insulin mRNA levels, supporting a
      novel synergistic and codependent relationship between exendin-4 signaling and
      TGF-beta isoform signaling.

PMID- 15504963
TI  - Palmitate stimulation of glucagon secretion in mouse pancreatic alpha-cells
      results from activation of L-type calcium channels and elevation of cytoplasmic
      calcium.
AB  - We have investigated the short-term effects of the saturated free fatty acid
      (FFA) palmitate on pancreatic alpha-cells. Palmitate (0.5 or 1 mmol/l bound to
      fatty acid-free albumin) stimulated glucagon secretion from intact mouse islets
      1.5- to 2-fold when added in the presence of 1-15 mmol/l glucose. Palmitate
      remained stimulatory in islets depolarized with 30 mmol/l extracellular K(+) or
      exposed to forskolin, but it did not remain stimulatory after treatment with
      isradipine or triacsin C. The stimulatory action of palmitate on secretion
      correlated with a 3.5-fold elevation of intracellular free Ca(2+) when applied in
      the presence of 15 mmol/l glucose, a 40% stimulation of exocytosis (measured as
      increases in cell capacitance), and a 25% increase in whole-cell Ca(2+) current.
      The latter effect was abolished by isradipine, suggesting that palmitate
      selectively modulates l-type Ca(2+) channels. The effect of palmitate on
      exocytosis was not mediated by palmitoyl-CoA, and intracellular application of
      this FFA metabolite decreased rather than enhanced Ca(2+)-induced exocytosis. The
      stimulatory effects of palmitate on glucagon secretion were paralleled by a
      approximately 50% inhibition of somatostatin release. We conclude that palmitate
      increases alpha-cell exocytosis principally by enhanced Ca(2+) entry via l-type
      Ca(2+) channels and, possibly, relief from paracrine inhibition by somatostatin
      released by neighboring delta-cells.

PMID- 15504965
TI  - Elevated alanine aminotransferase predicts new-onset type 2 diabetes
      independently of classical risk factors, metabolic syndrome, and C-reactive
      protein in the west of Scotland coronary prevention study.
AB  - We examined the association of serum alanine aminotransferase (ALT) with features
      of the metabolic syndrome and whether it predicted incident diabetes
      independently of routinely measured factors in 5,974 men in the West of Scotland
      Coronary Prevention Study. A total of 139 men developed new diabetes over 4.9
      years of follow-up. ALT, but not aspartate aminotransferase, levels increased
      progressively with the increasing number of metabolic syndrome abnormalities from
      (means +/- SD) 20.9 +/- 7.6 units/l in those with none to 28.1 +/- 10.1 units/l
      in those with four or more (P < 0.001). In a univariate analysis, men with ALT in
      the top quartile (ALT >/=29 units/l) had an elevated risk for diabetes (hazard
      ratio 3.38 [95% CI 1.99-5.73]) versus those in the bottom quartile (<17 units/l).
      ALT remained a predictor with adjustment for age, BMI, triglycerides, HDL
      cholesterol, systolic blood pressure, glucose, and alcohol intake (2.04 [1.16
      3.58] for the fourth versus first quartile). In stepwise regression,
      incorporating ALT and C-reactive protein (CRP) together with metabolic syndrome
      criteria, elevated ALT (>/=29 units/l), and CRP (>/=3 mg/l) predicted incident
      diabetes, but low HDL cholesterol and hypertension did not. Thus, elevated ALT
      levels within the "normal" range predict incident diabetes. The simplicity of ALT
      measurement and its availability in routine clinical practice suggest that this
      enzyme activity could be included in future diabetes prediction algorithms.

PMID- 15504964
TI  - Pioglitazone reduces islet triglyceride content and restores impaired glucose
      stimulated insulin secretion in heterozygous peroxisome proliferator-activated
      receptor-gamma-deficient mice on a high-fat diet.
AB  - Heterozygous peroxisome proliferator-activated receptor-gamma (PPAR-gamma)
      deficient (PPARgamma(+/-)) mice were protected from high-fat diet-induced insulin
      resistance. To determine the impact of systemic reduction of PPAR-gamma activity
      on beta-cell function, we investigated insulin secretion in PPARgamma(+/-) mice
      on a high-fat diet. Glucose-induced insulin secretion in PPARgamma(+/-) mice was
      impaired in vitro. The tissue triglyceride (TG) content of the white adipose
      tissue, skeletal muscle, and liver was decreased in PPARgamma(+/-) mice, but it
      was unexpectedly increased in the islets, and the increased TG content in the
      islets was associated with decreased glucose oxidation. Administration of a PPAR
      gamma agonist, pioglitazone, reduced the islet TG content in PPARgamma(+/-) mice
      on a high-fat diet and ameliorated the impaired insulin secretion in vitro. Our
      results demonstrate that PPAR-gamma protects islets from lipotoxicity by
      regulating TG partitioning among tissues and that a PPAR-gamma agonist can
      restore impaired insulin secretion under conditions of islet fat accumulation.

PMID- 15504966
TI  - A possible link between skeletal muscle mitochondrial efficiency and age-induced
      insulin resistance.
AB  - The transition from young to adult age is associated with decreased insulin
      sensitivity. To investigate whether changes in skeletal muscle mitochondrial
      function could be involved in the development of insulin resistance, we measured
      the oxidative capacity and energetic efficiency of subsarcolemmal and
      intermyofibrillar mitochondria isolated from the skeletal muscle of 60- and 180
      day-old rats. Mitochondrial efficiency was tested by measuring the degree of
      thermodynamic coupling and optimal thermodynamic efficiency, as well as
      mitochondrial proton leak, which was determined in both the absence (basal) and
      the presence (fatty acid induced) of palmitate. Serum glucose, insulin, and HOMA
      index were also measured. The results show that in adult rats, concomitant with
      increased HOMA index, skeletal muscle mitochondria display higher respiratory
      capacity and energy efficiency. In fact, thermodynamic coupling and optimal
      thermodynamic efficiency significantly increased and fatty acid-induced proton
      leak was significantly lower in the skeletal muscle mitochondria from adult than
      in younger rats. A deleterious consequence of increased mitochondrial efficiency
      would be a reduced utilization of energy substrates, especially fatty acids,
      leading to intracellular triglyceride accumulation and lipotoxicity, thus
      contributing to the onset of skeletal muscle insulin resistance.

PMID- 15504967
TI  - Impact of intra-abdominal fat and age on insulin sensitivity and beta-cell
      function.
AB  - The prevalence of glucose intolerance and type 2 diabetes increases with age. To
      determine whether the hyperbolic relationship between insulin sensitivity and the
      insulin response is affected by age and whether the decline in beta-cell function
      with age is related to increases in intra-abdominal fat or age per se, we studied
      220 healthy subjects with fasting glucose <6.1 mmol/l (89 men and 131 women, aged
      26-75 years, BMI 18.7-40.4 kg/m(2)). The insulin sensitivity index (S(i)) and the
      acute insulin response to glucose (AIRg) were determined, and from these beta
      cell function was estimated as the disposition index (S(i) x AIRg). Intra
      abdominal fat and subcutaneous fat areas were quantified by computed tomography.
      S(i) (5.40 +/- 0.5 vs. 7.86 +/- 0.7 x10(-5) min(-1)/[pmol/l]), P < 0.01) was
      decreased and intra-abdominal fat (117 +/- 10 vs. 81 +/- 9 cm(2), P < 0.05) was
      increased in the oldest (age 60-75 years) versus the youngest (age 26-44 years)
      quartile. The hyperbolic relationship between S(i) and AIRg was present
      independent of age; thus, beta-cell function measured as the disposition index
      (1,412 +/- 120 vs. 2,125 +/- 150 x10(-5) min(-1), P < 0.01) was lower in the
      oldest versus the youngest quartile. In multiple regression, intra-abdominal fat
      (r = -0.470, P < 0.001) but not age was associated with S(i), but both intra
      abdominal fat (r = -0.198, P = 0.003) and age (r = -0.131, P = 0.05) were
      correlated with the disposition index. These data suggest that although intra
      abdominal fat is a strong determinant of insulin sensitivity and beta-cell
      function, age has an independent effect on beta-cell function that may contribute
      to the increased prevalence of type 2 diabetes in older populations.

PMID- 15504968
TI  - Free fatty acid levels modulate microvascular function: relevance for obesity
      associated insulin resistance, hypertension, and microangiopathy.
AB  - To test the hypothesis that free fatty acids (FFAs) modulate microvascular
      function and that this contributes to obesity-associated insulin resistance,
      hypertension, and microangiopathy, we examined the effects of both FFA elevation
      in lean women and FFA lowering in obese women on skin microvascular function. A
      total of 16 lean and 12 obese women underwent, respectively, Intralipid plus
      heparin (or saline) infusion and overnight acipimox (or placebo) treatment. We
      measured capillary recruitment with capillaroscopy and endothelium-(in)dependent
      vasodilation by iontophoresis of acetylcholine and sodium nitroprusside before
      and during hyperinsulinemia (40 mU . m(-2) . min(-1)). FFA elevation impaired
      capillary recruitment and acetylcholine-mediated vasodilation before (44.6 +/-
      16.8 vs. 56.9 +/- 18.9%, P < 0.05; and 338 +/- 131 vs. 557 +/- 162%, P < 0.01,
      respectively) and during (54.0 +/- 21.3 vs. 72.4 +/- 25.4%, P < 0.01; and 264 +/-
      186 vs. 685 +/- 199%, P < 0.01, respectively) hyperinsulinemia. FFA lowering
      improved capillary recruitment before (50.9 +/- 14.6 vs. 37.4 +/- 9.3%, P < 0.01)
      and during (66.8 +/- 20.6 vs. 54.8 +/- 15.4%, P < 0.05) hyperinsulinemia. Changes
      in FFA levels were inversely associated with changes in capillary recruitment and
      insulin sensitivity in lean (r = -0.46, P = 0.08; and r = -0.56, P = 0.03) and in
      obese (r = -0.70, P = 0.02; and r = -0.62, P = 0.04) women. Regression analyses
      showed that changes in capillary recruitment statistically explained
      approximately 29% of the association between changes in FFA levels and insulin
      sensitivity. In conclusion, FFA levels modulate microvascular function and may
      contribute to obesity-associated insulin resistance, hypertension, and
      microangiopathy.

PMID- 15504969
TI  - A prospective study of serum lipids and risk of diabetic macular edema in type 1
      diabetes.
AB  - We evaluated the relationships between serum lipid levels and clinically
      significant macular edema (CSME), hard exudates, and other diabetic retinopathy
      (DR) end points in a population with type 1 diabetes. We studied data from serum
      lipids that were measured annually among the 1,441 Diabetes Control and
      Complications Trial (DCCT) participants. We used proportional hazards regression
      models to examine the relationship of the cumulative average of lipid levels
      (total, LDL, and HDL cholesterol, total-to-HDL cholesterol ratio, and
      triglycerides) with development of CSME, hard exudate, DR progression, and
      development of proliferative DR (PDR). In models controlling for primary
      prevention versus secondary intervention subgroup, randomized treatment
      assignment, HbA(1c), and other risk factors, both total-to-HDL cholesterol ratio
      and LDL predicted development of CSME (rate ratio [RR] for extreme quintiles
      3.84, P for trend = 0.03 for total-to-HDL cholesterol ratio, and RR 1.95, P for
      trend = 0.03 for LDL) and hard exudate (RR 2.44, P for trend = 0.0004 for total
      to-HDL cholesterol ratio, and RR 2.77, P for trend = 0.002 for LDL).
      Relationships of lipids with progression of DR and development of PDR were weaker
      and not significant after adjustment for HbA(1c). Higher serum lipids are
      associated with increased risk of CSME and retinal hard exudate. Lipid-lowering
      treatment among type 1 diabetic subjects, recommended to prevent cardiovascular
      disease, may also decrease risk of CSME, an important cause of vision loss.

PMID- 15504970
TI  - Hepatic lipase mRNA, protein, and plasma enzyme activity is increased in the
      insulin-resistant, fructose-fed Syrian golden hamster and is partially normalized
      by the insulin sensitizer rosiglitazone.
AB  - Postheparin plasma hepatic lipase (HL) activity has been shown to correlate with
      features of the metabolic syndrome and type 2 diabetes in humans. We examined HL
      postheparin plasma enzyme activity, hepatocyte mRNA, and protein mass in the
      insulin-resistant, fructose-fed Syrian golden hamster, and the response of the
      insulin-sensitizing peroxisome proliferator-activated receptor-gamma agonist
      rosiglitazone. Male Syrian golden hamsters were treated for 5 weeks with 1)
      normal diet (DIET group), 2) 60% fructose diet (FRUC group), or 3) 60% fructose
      and rosiglitazone (20 mmol . kg(-1) . day(-1)) (FRUC+RSG group). Hepatocyte HL
      mRNA, protein mass, and postheparin plasma HL activity were increased in FRUC
      compared with DIET hamsters. FRUC+RSG hamsters had partial normalization of HL
      mRNA, mass, and activity. There was a shift in the size of LDL particles from
      large to small in FRUC animals and a shift back to large LDL size in FRUC+RSG.
      This is the first demonstration that HL hepatocyte mRNA, mass, and plasma
      enzymatic activity increase concomitantly with induction of an insulin-resistant
      state and can be partially normalized by treatment with an insulin sensitizer.
      The increase in HL in insulin-resistant states may play an important role in the
      typical dyslipidemia of these conditions, and reduction of HL could explain some
      of the beneficial effects of insulin sensitizers on the plasma lipid profile.

PMID- 15504971
TI  - Phloridzin improves hyperglycemia but not hepatic insulin resistance in a
      transgenic mouse model of type 2 diabetes.
AB  - The chronic hyperglycemia that occurs in type 2 diabetes may cause deterioration
      of beta-cell function and insulin resistance in peripheral tissues. Mice that
      express a dominant-negative IGF-1 receptor, specifically in skeletal muscle (MKR
      mice), exhibit severe insulin resistance, hyperinsulinemia, dyslipidemia, and
      hyper-glycemia. To determine the role of hyperglycemia in the worsening of the
      diabetes state in these animals, MKR mice were treated with phloridzin (PHZ),
      which inhibits intestinal glucose uptake and renal glucose reabsorption. Blood
      glucose levels were decreased and urine glucose levels were increased in response
      to PHZ treatment in MKR mice. PHZ treatment also increased food intake in MKR
      mice; however, the fat mass was decreased and lean body mass did not change.
      Serum insulin, fatty acid, and triglyceride levels were not affected by PHZ
      treatment in MKR mice. Hyperinsulinemic-euglycemic clamp analysis demonstrated
      that glucose uptake in white adipose tissue was significantly increased in
      response to PHZ treatment. Despite the reduction in blood glucose following PHZ
      treatment, there was no improvement in insulin-stimulated whole-body glucose
      uptake in MKR mice and neither was there suppression of endogenous glucose
      production by insulin. These results suggest that glucotoxicity plays little or
      no role in the worsening of insulin resistance that occurs in the MKR mouse model
      of type 2 diabetes.

PMID- 15504972
TI  - Activation of nuclear factor-kappaB by hyperglycemia in vascular smooth muscle
      cells is regulated by aldose reductase.
AB  - Activation of the polyol pathway has been linked to the development of secondary
      diabetic complications. However, the underlying molecular mechanisms remain
      unclear. To probe the contribution of this pathway, we examined whether
      inhibition of aldose reductase, which catalyzes the first step of the pathway,
      affects hyperglycemia-induced activation of the inflammatory transcription factor
      nuclear factor (NF)-kappaB. Treatment of vascular smooth muscle cells with the
      aldose reductase inhibitors tolrestat and sorbinil prevented high-glucose-induced
      protein kinase C (PKC) activation, nuclear translocation of NF-kappaB,
      phosphorylation of IKK, and the increase in the expression of intracellular
      adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and aldose
      reductase. High-glucose-induced NF-kappaB activation was also prevented by the
      PKC inhibitors chelerythrine and calphostin C. Ablation of aldose reductase by
      small interference RNA (siRNA) prevented high-glucose-induced NF-kappaB and AP-1
      activation but did not affect the activity of SP-1 or OCT-1. Stimulation with iso
      osmotic mannitol activated NF-kappaB and increased the expression of aldose
      reductase but not ICAM-1 and VCAM-1. Treatment with aldose reductase inhibitors
      or aldose reductase siRNA did not affect mannitol-induced NF-kappaB or AP-1
      activation. Administration of tolrestat (15 mg . kg(-1) . day(-1)) decreased the
      abundance of activated NF-kappaB in balloon-injured carotid arteries of diabetic
      rats. Collectively, these results suggest that inhibition of aldose reductase,
      which prevents PKC-dependent nonosmotic NF-kappaB activation, may be a useful
      approach for treating vascular inflammation caused by diabetes.

PMID- 15504973
TI  - Attenuation of extracellular matrix accumulation in diabetic nephropathy by the
      advanced glycation end product cross-link breaker ALT-711 via a protein kinase C
      alpha-dependent pathway.
AB  - This study investigated the role of advanced glycation end products (AGEs) in
      mediating protein kinase C (PKC) isoform expression in diabetic nephropathy. In
      vitro, vascular smooth muscle cells incubated in a high-glucose (25-mmol/l)
      medium demonstrated translocation and increased expression of PKC-alpha as
      compared with those from a low-glucose (5-mmol/l) environment. Coincubation with
      the cross-link breaker ALT-711 and, to a lesser extent, with aminoguanidine, an
      inhibitor of AGE formation, attenuated the increased expression and translocation
      of PKC-alpha. Streptozotocin-induced diabetic rats were randomized to no
      treatment, treatment with ALT-711, or treatment with aminoguanidine. Diabetes
      induced increases in PKC-alpha as well as in the -betaI, -betaII, and -epsilon
      isoforms. Treatment with ALT-711 and aminoguanidine, which both attenuate renal
      AGE accumulation, abrogated these increases in PKC expression. However,
      translocation of phosphorylated PKC-alpha from the cytoplasm to the membrane was
      reduced only by ALT-711. ALT-711 treatment attenuated expression of vascular
      endothelial growth factor and the extracellular matrix proteins, fibronectin and
      laminin, in association with reduced albuminuria. Aminoguanidine had no effect on
      VEGF expression, although some reduction of fibronectin and laminin was observed.
      These findings implicate AGEs as important stimuli for the activation of PKC,
      particularly PKC-alpha, in the diabetic kidney, which can be directly inhibited
      by ALT-711.

PMID- 15504974
TI  - Interactions between hyperglycemia and hypoxia: implications for diabetic
      retinopathy.
AB  - The primary aim of these experiments was to assess in vitro effects of
      hyperglycemia (30 mmol/l glucose) and hypoxia (Po(2) = 36 torr) of 2-h duration,
      separately and in combination, on cytosolic and mitochondrial free NADH (NADHc
      and NADHm, respectively) in retinas from normal rats. NADH is the major carrier
      of electrons and protons that fuel ATP synthesis and several metabolic pathways
      linked to diabetic complications. Hyperglycemia and hypoxia increase free NADHc
      by different mechanisms that are additive. Hyperglycemia increases transfer of
      electrons and protons from sorbitol to NAD(+)c, reducing it to NADHc, but does
      not increase NADHm. Hypoxia increases NADHm by inhibiting its oxidation.
      Electrons and protons accumulating in NADHm restrain transfer of electrons and
      protons from NADHc to NAD(+)m via the malate-aspartate electron shuttle.
      Hyperglycemia and hypoxia also increase glycolysis by different mechanisms that
      are additive, and hyperglycemia increases ATP levels in hypoxic and in aerobic
      retinas. The additive effects of hyperglycemia and hypoxia on accumulation of
      electrons and protons in a common pool of free NADHc confirm the test hypothesis
      and the potential of a combination of these two risk factors to accelerate the
      onset and progression of diabetic retinopathy (and other complications of
      diabetes) by augmenting metabolic pathways fueled by free NADHc.

PMID- 15504975
TI  - Podocyte-derived vascular endothelial growth factor mediates the stimulation of
      alpha3(IV) collagen production by transforming growth factor-beta1 in mouse
      podocytes.
AB  - Podocyte-derived vascular endothelial growth factor (VEGF) is upregulated in
      diabetes and may contribute to albuminuria. Although believed to act upon the
      glomerular endothelium, VEGF may have pronounced effects on the podocyte itself.
      The functionality of this VEGF autocrine loop was investigated in conditionally
      immortalized mouse podocytes. Exogenous VEGF(164) increased the production of
      alpha3(IV) collagen, an integral component of the glomerular basement membrane
      (GBM); this effect was completely prevented by SU5416, a pan-VEGF receptor
      inhibitor. The VEGF inhibitor also partially prevented the stimulation of
      alpha3(IV) collagen by transforming growth factor (TGF)-beta1, establishing a
      novel role for endogenous VEGF. However, VEGF did not influence the production of
      another novel chain of collagen IV, alpha5(IV) collagen, and SU5416 failed to
      reverse the known inhibitory effect of TGF-beta1 on alpha5(IV) collagen
      production. Cultured mouse podocytes possess at least the VEGFR-1 receptor,
      confirmed by RT-PCR, immunoblotting, and immunocytochemistry. By these
      techniques, however, VEGFR-2 is absent. VEGF signaling proceeds via
      autophosphorylation of VEGFR-1 and activation of the phosphatidylinositol 3
      kinase (PI3K) pathway. Thus, podocyte-derived VEGF operates in an autocrine loop,
      likely through VEGFR-1 and PI3K, to stimulate alpha3(IV) collagen production. The
      TGF-beta1-stimulated endogenous VEGF may have significant implications for
      podocyte dysfunction in diabetic glomerulopathy, manifesting as GBM thickening
      and altered macromolecular permeability.

PMID- 15504976
TI  - Leukocyte-derived myeloperoxidase amplifies high-glucose--induced endothelial
      dysfunction through interaction with high-glucose--stimulated, vascular non-
      leukocyte-derived reactive oxygen species.
AB  - Vascular non-leukocyte-derived reactive oxygen species (ROS), such as superoxide
      and hydrogen peroxide (H(2)O(2)), have emerged as important molecules in diabetic
      endothelial dysfunction. In addition, leukocyte-derived myeloperoxidase (MPO) has
      been implicated in vascular injury, and its injury response is H(2)O(2)
      dependent. It is well known that MPO can use leukocyte-derived H(2)O(2); however,
      it is unknown whether the vascular-bound MPO can use high-glucose-stimulated,
      vascular non-leukocyte-derived H(2)O(2) to induce diabetic endothelial
      dysfunction. In the present study, we demonstrated that MPO activity is increased
      in vessels from diabetic rats. In high-glucose-incubated rat aortas and in
      carotid arteries from rats with acute hyperglycemia, vascular-bound MPO utilized
      high-glucose-stimulated H(2)O(2) to amplify the ROS-induced impairment of
      endothelium-dependent relaxation via reduction of nitric oxide bioavailability.
      Hypochlorous acid (HOCL)-modified LDL, a specific biomarker for the
      MPO/HOCL/chlorinating species pathway, was detected in LDL- and MPO-bound vessels
      with high-glucose-stimulated H(2)O(2). The results suggest that vascular-bound
      MPO could use high-glucose-stimulated H(2)O(2) to amplify high-glucose-induced
      injury in the vascular wall. MPO/H(2)O(2)/HOCL/chlorinating species may represent
      an important pathway in diabetes complications and a new mechanism in phagocyte-
      and systemic infection-induced exacerbation of diabetic vascular diseases.

PMID- 15504977
TI  - Poly(ADP-ribose) polymerase is involved in the development of diabetic
      retinopathy via regulation of nuclear factor-kappaB.
AB  - The current study investigated the role of poly(ADP-ribose) polymerase (PARP) in
      the development of diabetic retinopathy. Activity of PARP was increased in whole
      retina and in endothelial cells and pericytes of diabetic rats. Administration of
      PJ-34 (a potent PARP inhibitor) for 9 months to diabetic rats significantly
      inhibited the diabetes-induced death of retinal microvascular cells and the
      development of early lesions of diabetic retinopathy, including acellular
      capillaries and pericyte ghosts. To further investigate how PARP activation leads
      to cell death in diabetes, we investigated the possibility that PARP acts as a
      coactivator of nuclear factor-kappaB (NF-kappaB) in the retinal cells. In bovine
      retinal endothelial cells (BRECs), PARP interacted directly with both subunits of
      NF-kappaB (p50 and p65). More PARP was complexed to the p50 subunit in elevated
      glucose concentration (25 mmol/l) than at 5 mmol/l glucose. PJ-34 blocked the
      hyperglycemia-induced increase in NF-kappaB activation in BRECs. PJ-34 also
      inhibited diabetes-induced increase expression of intercellular adhesion molecule
      1, a product of NF-kappaB-dependent transcription in retina, and subsequent
      leukostasis. Inhibition of PARP or NF-kappaB inhibited the hyperglycemia (25
      mmol/l glucose)-induced cell death in retinal endothelial cells. Thus, PARP
      activation plays an important role in the diabetes-induced death of retinal
      capillary cells, at least in part via its regulation of NF-kappaB.

PMID- 15504978
TI  - Tumor necrosis factor-alpha in diabetic plasma increases the activity of core 2
      GlcNAc-T and adherence of human leukocytes to retinal endothelial cells:
      significance of core 2 GlcNAc-T in diabetic retinopathy.
AB  - A large body of evidence now implicates increased leukocyte-endothelial cell
      adhesion as a key early event in the development of diabetic retinopathy. We
      recently reported that raised activity of the glycosylating enzyme core 2 beta
      1,6-N-acetylglucosaminyltransferase (GlcNAc-T) through protein kinase C
      (PKC)beta2-dependent phosphorylation plays a fundamental role in increased
      leukocyte-endothelial cell adhesion and capillary occlusion in retinopathy. In
      the present study, we demonstrate that following exposure to plasma from diabetic
      patients, the human promonocytic cell line U937 exhibits a significant elevation
      in core 2 GlcNAc-T activity and increased adherence to cultured retinal capillary
      endothelial cells. These effects of diabetic plasma on enzyme activity and cell
      adhesion, mediated by PKCbeta2-dependent phosphorylation of the core 2 GlcNAc-T
      protein, were found to be triggered by increased plasma levels of tumor necrosis
      factor (TNF)-alpha. Levels of enzyme activity in plasma-treated U937 cells were
      closely dependent on the severity of diabetic retinopathy, with the highest
      values observed upon treatment with plasma of patients affected by proliferative
      retinopathy. Furthermore, we noted much higher correlation, as compared with
      control subjects, between increased values of core 2 GlcNAc-T activity and cell
      adhesion properties. Based on the prominent role of TNF-alpha in the development
      of diabetic retinopathy, these observations further validate the significance of
      core 2 GlcNAc-T in the pathogenesis of capillary occlusion, thereby enhancing the
      therapeutic potential of specific enzyme inhibitors.

PMID- 15504979
TI  - Genetics of the APM1 locus and its contribution to type 2 diabetes susceptibility
      in French Caucasians.
AB  - We have carried out a detailed reexamination of the genetics of the APM1 locus
      and its contribution to the genetic basis of type 2 diabetes susceptibility in
      the French Caucasian population. The G allele of single nucleotide polymorphism 
      11426 in the APM1 promoter showed modest association with type 2 diabetes (odds
      ratio 1.44 [95% CI 1.04-1.98]; P = 0.03), providing corroborative evidence that
      single nucleotide polymorphisms in the APM1 promoter region contribute to the
      genetic risk of type 2 diabetes. A "sliding window" analysis identified
      haplotypes 1-1-1, 1-1-1-1, and 1-1-1-1-1 as being strongly protective against
      type 2 diabetes (P </= 0.0001). Evidence is presented that the APM1 gene is a
      locus of low linkage disequilibrium, high haplotype diversity, and high
      recombination. We were unable to obtain data to support the hypothesis that
      genetic variation in the APM1 gene is a major contributor to the type 2 diabetes
      linkage result at chromosome 3q27. Finally, in families with early-onset type 2
      diabetes, we obtained suggestive evidence of a linkage peak for serum adiponectin
      levels (logarithm of odds = 2.1) that closely matched the position of the type 2
      diabetes linkage peak. This result indicated that the type 2 diabetes
      susceptibility locus at 3q27 influences both genetic predisposition to type 2
      diabetes and serum adiponectin levels in patients with type 2 diabetes.

PMID- 15504980
TI  - Association of glomerulopathy with the 5'-end polymorphism of the aldose
      reductase gene and renal insufficiency in type 2 diabetic patients.
AB  - The expression of nephropathy in type 2 diabetes has several levels of
      abnormalities. To define the primary abnormalities of diabetic nephropathy, we
      conducted an autopsy study of 186 consecutive patients with type 2 diabetes to
      determine correlations among the aldose reductase gene, renal histopathologies,
      extracellular matrix, glomerular function, and clinical characteristics. Compared
      with cases of near-normal renal structure (n = 51) and atypical diabetic
      glomerulopathy (n = 75), patients with classic diabetic glomerulopathy (n = 60)
      had advanced glomerular disease, as reflected by elevated plasma creatinine
      levels (133.2 +/- 59.8 vs. 166.0 +/- 65.7 vs. 243.8 +/- 82.6 micromol/l; P <
      0.001), glomerular matrix fractions (20.8 +/- 6.7 vs. 33.5 +/- 16.8 vs. 39.2 +/-
      14.3%; P < 0.001), and risk of renal failure (odds ratio [OR] 1 vs. 3.5 vs. 21.4;
      P < 0.001). Compared with noncarriers of the aldose reductase z-2 allele (n = 92)
      and z-2 heterozygotes (n = 77), z-2 homozygotes (n = 17) had elevated plasma
      creatinine (164.1 +/- 73.7 vs. 190.6 +/- 60.9 vs. 241.1 +/- 86.2 micromol/l; P <
      0.001) and an increased risk of classic diabetic glomerulopathy (OR 1 vs. 0.9 vs.
      3.3; P = 0.026). Overexpression of transforming growth factor-beta1, mesangial
      cell transdifferentiation by expression of alpha-smooth muscle actin, and
      aberrant deposition of collagen type IV, fibronectin, and laminin were found in
      classic diabetic glomerulopathy. These data suggest genetic, biochemical,
      pathophysiological, and clinical correlations among the aldose reductase gene,
      extracellular matrix, classic diabetic glomerulopathy, and renal insufficiency.
      Gene mutation, cellular transdifferentiation, growth factor upregulation,
      extracellular matrix expansion, and glomerular filtration impairment are the
      primary abnormalities in type 2 diabetic patients with nephropathy.

PMID- 15504981
TI  - Variation in NCB5OR: studies of relationships to type 2 diabetes, maturity-onset
      diabetes of the young, and gestational diabetes mellitus.
AB  - Recent data show that homozygous Ncb5or(-/-) knock-out mice present with an early
      onset nonautoimmune diabetes phenotype. Furthermore, genome-wide scans have
      reported linkage to the chromosome 6q14.2 region close to the human NCB5OR. We
      therefore considered NCB5OR to be a biological and positional candidate gene and
      examined the coding region of NCB5OR in 120 type 2 diabetic patients and 63
      patients with maturity-onset diabetes of the young using denaturing high
      performance liquid chromatography. We identified a total of 22 novel nucleotide
      variants. Three variants [IVS5+7del(CT), Gln187Arg, and His223Arg] were genotyped
      in a case-control design comprising 1,246 subjects (717 type 2 diabetic patients
      and 529 subjects with normal glucose tolerance). In addition, four rare variants
      were investigated for cosegregation with diabetes in multiplex type 2 diabetic
      families. The IVS5+7del(CT) variant was associated with common late-onset type 2
      diabetes; however, we failed to relate this variant to any diabetes-related
      quantitative traits among the 529 control subjects. Thus, variation in the coding
      region of NCB5OR is not a major contributor in the pathogenesis of nonautoimmune
      diabetes.

PMID- 15504982
TI  - Activating mutations in the KCNJ11 gene encoding the ATP-sensitive K+ channel
      subunit Kir6.2 are rare in clinically defined type 1 diabetes diagnosed before 2
      years.
AB  - We have recently shown that permanent neonatal diabetes can be caused by
      activating mutations in KCNJ11 that encode the Kir6.2 subunit of the beta-cell
      ATP-sensitive K(+) channel. Some of these patients were diagnosed after 3 months
      of age and presented with ketoacidosis and marked hyperglycemia, which could have
      been diagnosed as type 1 diabetes. We hypothesized that KCNJ11 mutations could
      present clinically as type 1 diabetes. We screened the KCNJ11 gene for mutations
      in 77 U.K. type 1 diabetic subjects diagnosed under the age of 2 years. One
      patient was found to be heterozygous for the missense mutation R201C. She had low
      birth weight, was diagnosed at 5 weeks, and did not have a high risk predisposing
      HLA genotype. A novel variant, R176C, was identified in one diabetic subject but
      did not cosegregate with diabetes within the family. In conclusion, we have shown
      that heterozygous activating mutations in the KCNJ11 gene are a rare cause of
      clinically defined type 1 diabetes diagnosed before 2 years. Although activating
      KCNJ11 mutations are rare in patients diagnosed with type 1 diabetes, the
      identification of a KCNJ11 mutation may have important treatment implications.

PMID- 15504983
TI  - Common variants of the hepatocyte nuclear factor-4alpha P2 promoter are
      associated with type 2 diabetes in the U.K. population.
AB  - Hepatocyte nuclear factor (HNF)-4alpha is part of a transcription factor network
      that is key for the development and function of the beta-cell. Rare mutations in
      the HNF4alpha gene cause maturity-onset diabetes of the young. A number of type 2
      diabetes linkage studies have found evidence of linkage to 20q12-13.1 where the
      HNF4alpha gene is located. Two recent studies have found an association between
      four common variants of the alternative P2 promoter region and type 2 diabetes.
      These variants are in strong linkage disequilibrium, and the minor alleles define
      one common risk haplotype. In both studies, the risk haplotype explained a large
      proportion of the evidence of linkage to 20q12-13.1. We aimed to assess this
      haplotype in a U.K. Caucasian study of 5,256 subjects. We typed two single
      nucleotide polymorphisms tagging the risk haplotype (rs4810424 and rs2144908) and
      found evidence of association in both case-control and family-based studies;
      rs4810424 marginally demonstrated the stronger association with an overall
      estimated odds ratio of 1.15 (95% CI 1.02-1.33) (P = 0.02). The effect of the P2
      haplotype on type 2 diabetes risk is less than in the initial studies, probably
      reflecting that these studies used 20q12-13.1-linked cases. In conclusion, we
      have replicated the association of the HNF4alpha P2 promoter haplotype with type
      2 diabetes in a U.K. Caucasian population where there is no evidence of linkage
      to 20q.

PMID- 15504984
TI  - Association of protein tyrosine phosphatase 1B gene polymorphisms with type 2
      diabetes.
AB  - The PTPN1 gene codes for protein tyrosine phosphatase 1B (PTP1B) (EC 3.1.3.48),
      which negatively regulates insulin signaling by dephosphorylating the
      phosphotyrosine residues of the insulin receptor kinase activation segment. PTPN1
      is located in 20q13, a genomic region linked to type 2 diabetes in multiple
      genetic studies. Surveys of the gene have previously identified only a few
      uncommon coding single nucleotide polymorphisms (SNPs). We have carried out a
      detailed association analysis of 23 noncoding SNPs spanning the 161-kb genomic
      region, which includes the PTPN1 gene. These SNPs have been assessed for
      association with type 2 diabetes in two independently ascertained collections of
      Caucasian subjects with type 2 diabetes and two control groups. Association is
      observed between multiple SNPs and type 2 diabetes. The most consistent evidence
      for association occurred with SNPs spanning the 3' end of intron 1 of PTPN1
      through intron 8 (P values ranging from 0.043 to 0.004 in one case-control set
      and 0.038-0.002 in a second case-control set). Analysis of the combined case
      control data increased the evidence of SNP association with type 2 diabetes (P =
      0.005-0.0016). All of the associated SNPs lie in a single 100-kb haplotype block
      that encompasses the PTPN1 gene. Analysis of haplotypes indicates a significant
      difference between haplotype frequencies in type 2 diabetes case and control
      subjects (P = 0.0035-0.0056), with one common haplotype (36%) contributing
      strongly to the evidence for association with type 2 diabetes. Odds ratios
      calculated from single SNP or haplotype data are in the proximity of 1.3.
      Haplotype-based calculation of population-attributable risk (PAR) results in an
      estimated PAR of 17-20% based on different models and assumptions. These results
      suggest that PTPN1 is a significant contributor to type 2 diabetes susceptibility
      in the Caucasian population. This risk is likely due to noncoding polymorphisms.

PMID- 15504985
TI  - Association of protein tyrosine phosphatase 1B gene polymorphisms with measures
      of glucose homeostasis in Hispanic Americans: the insulin resistance
      atherosclerosis study (IRAS) family study.
AB  - Protein tyrosine phosphatase (PTP)-1B, encoded by the PTPN1 gene, catalyzes the
      dephosphorylation of proteins at tyrosyl residues. PTP-1B has been implicated in
      negatively regulating insulin signaling by dephosphorylating the phosphotyrosine
      residues of the insulin receptor. The genetic contribution of PTPN1 to measures
      of glucose homeostasis has been assessed in 811 Hispanic subjects from the
      Insulin Resistance Atherosclerosis Study Family Study (IRASFS). Thirty-five
      single nucleotide polymorphisms (SNPs) spanning 161 kb and containing the PTPN1
      gene were genotyped and tested for association. All 20 SNPs with minor allele
      frequencies >0.1 in a single haplotype block covering the PTPN1 genomic sequence
      show significant association with the insulin sensitivity index (S(i)) (P = 0.044
      0.003) and fasting glucose (P = 0.029 to <0.001). In contrast, there is no
      evidence for association of PTPN1 polymorphisms with acute insulin response (a
      measure of beta-cell function). Haplotype analysis of eight SNP haplotypes that
      have independently been shown to be associated with type 2 diabetes risk and
      protection in Caucasian type 2 diabetic subjects are associated with lower (P =
      0.007) and higher (P = 0.0002) S(i) and higher (P = 0.00007) and lower (P =
      0.001) fasting glucose, respectively, in the IRASFS. This comprehensive genetic
      analysis of PTPN1 reveals significant association with metabolic traits
      consistent with the proposed in vivo role for the PTP-1B protein.

PMID- 15504986
TI  - Replication of an association between the lymphoid tyrosine phosphatase locus
      (LYP/PTPN22) with type 1 diabetes, and evidence for its role as a general
      autoimmunity locus.
AB  - In the genetic analysis of common, multifactorial diseases, such as type 1
      diabetes, true positive irrefutable linkage and association results have been
      rare to date. Recently, it has been reported that a single nucleotide
      polymorphism (SNP), 1858C>T, in the gene PTPN22, encoding Arg620Trp in the
      lymphoid protein tyrosine phosphatase (LYP), which has been shown to be a
      negative regulator of T-cell activation, is associated with an increased risk of
      type 1 diabetes. Here, we have replicated these findings in 1,388 type 1 diabetic
      families and in a collection of 1,599 case and 1,718 control subjects, confirming
      the association of the PTPN22 locus with type 1 diabetes (family-based relative
      risk (RR) 1.67 [95% CI 1.46-1.91], and case-control odds ratio (OR) 1.78 [95% CI
      1.54-2.06]; overall P = 6.02 x 10(-27)). We also report evidence for an
      association of Trp(620) with another autoimmune disorder, Graves' disease, in
      1,734 case and control subjects (P = 6.24 x 10(-4); OR 1.43 [95% CI 1.17-1.76]).
      Taken together, these results indicate a more general association of the PTPN22
      locus with autoimmune disease.

PMID- 15504987
TI  - Intranasal insulin reduces body fat in men but not in women.
AB  - Insulin acts in the central nervous system to reduce food intake and body weight
      and is considered a major adiposity signal. After intranasal administration,
      insulin enters the cerebrospinal fluid compartment and alters brain functions in
      the absence of substantial absorption into the blood stream. Here we report the
      effects of 8 weeks of intranasal administration of insulin (4 x 40 IU/day) or
      placebo to two groups of healthy human subjects (12 men and 8 women in each
      group). The insulin-treated men lost 1.28 kg body wt and 1.38 kg of body fat, and
      their waist circumference decreased by 1.63 cm. Plasma leptin levels dropped by
      an average of 27%. In contrast, the insulin-treated women did not lose body fat
      and gained 1.04 kg body wt due to a rise in extracellular water. Our results
      provide a strong, first confirmation in humans that insulin acts as a negative
      feedback signal in the regulation of adiposity and point to a differential
      sensitivity to the catabolic effects of insulin based on sex.

PMID- 15504988
TI  - Severe hypo-alpha-lipoproteinemia during treatment with rosiglitazone.
AB  - Thiazolidinedione drugs are in widespread use for the treatment of type 2
      diabetes. In addition to improving insulin sensitivity, they generally result in
      a modest elevation of plasma HDL cholesterol. We report three patients, all of
      whom had preexisting diabetic dyslipidemia, who showed a profound reduction in
      plasma HDL cholesterol and apolipoprotein AI levels soon after the initiation of
      rosiglitazone therapy. In all three patients, HDL cholesterol levels returned to
      normal following drug withdrawal. The fact that this phenomenon was not seen in
      >1,400 patients studied in clinical trials indicates that it is likely to be rare
      and idiosyncratic. Until the frequency of this adverse reaction is clearer, it
      would seem advisable to ensure that plasma HDL cholesterol is documented before
      and rechecked after commencement of thiazolidinedione therapy.

PMID- 15504989
TI  - Reduced hospitalizations and death associated with influenza vaccination among
      patients with and without diabetes.
AB  - OBJECTIVE: To assess whether the influenza vaccination of community-dwelling,
      diabetic, elderly individuals is associated with reduced rates of hospitalization
      and death. RESEARCH DESIGN AND METHODS: In this outcome-research study, we
      compared mortality and hospitalization rates of 15,556 patients aged >or=65 years
      followed using a diabetes registry in a large health maintenance organization to
      that of 69,097 members not suffering from chronic disease who were considered as
      a reference group. The study outcomes included all-cause death and
      hospitalization in internal medicine or geriatric wards for any reason over
      winter and summer (control) periods. RESULTS: Vaccination rates were 48.8 and
      42.0% among patients with diabetes and the reference population, respectively.
      Influenza vaccination was associated with a 12.3% reduction in hospitalization
      rates for patients with diabetes compared with 23.0% in the reference group (P =
      0.08). The reduction in hospitalization rates was similar in both sexes among
      patients with diabetes. In addition, there was a significant reduction in
      mortality for the vaccinated group of patients with diabetes when compared with
      the nonvaccinated group except for female patients aged >or=85 years.
      CONCLUSIONS: The study results support the use of influenza vaccine among an
      elderly population. However, there does not appear to be an additional benefit
      for patients with diabetes.

PMID- 15504990
TI  - Effect of rosiglitazone versus insulin on the pancreatic beta-cell function of
      subjects with type 2 diabetes.
AB  - OBJECTIVE: In a previous study, we found observational evidence of improvement in
      beta-cell function when rosiglitazone was added to a failing oral
      antihyperglycemic regimen consisting of sulfonylureas and metformin. To confirm
      our previous observations, we designed and performed a prospective, randomized,
      and controlled study. RESEARCH DESIGN AND METHODS: A total of 17 subjects with
      type 2 diabetes, inadequately controlled on a maximized oral antihyperglycemic
      double regimen of glimepiride and metformin, were randomized to the addition of
      rosiglitazone or insulin to their treatment regimens for a period of 6 months. At
      baseline and at 6 months, the following were performed: measurement of fasting
      plasma glucose, fasting proinsulin, and insulin levels; frequently sampled
      intravenous glucose tolerance test; and glucagon stimulation test for C-peptide.
      RESULTS: Nine subjects were randomized to the addition of 8 mg rosiglitazone, and
      eight subjects were randomized to the addition of one injection of insulin
      (premixed 70/30) before their evening meal. The treatment groups were well
      matched for age, duration of diabetes, and BMI. Most important, the HbA(1c) was
      well matched between groups before treatment (8.7 +/- 0.3 and 9.0 +/- 0.3%; NS)
      and at the end of the 6 months (7.8 +/- 0.5 and 7.8 +/- 0.3%; NS). After 6
      months, at the end of the study, there was a significant improvement in acute
      insulin response to glucose in the rosiglitazone group (+15.3 microIU x ml(-1) x
      10 min(-1); P < 0.001) that led to an increase in the disposition index from 0.18
      at baseline to 4.18 at 6 months (P = 0.02). Furthermore, at the end of the study,
      the proinsulin-to-insulin ratio had decreased in the rosiglitazone group by 36%
      (P = 0.03) but did not change significantly in the insulin treatment group.
      CONCLUSIONS: Rosiglitazone, but not insulin, induced a recovery of pancreatic
      beta-cell function, as evidenced by the restoration of the first-phase insulin
      response to glucose, improvement in the disposition index, and a decrease in the
      proinsulin-to-insulin ratio in subjects with type 2 diabetes in whom oral
      antihyperglycemic therapy failed. This improvement was independent of the
      correction of glucotoxicity.

PMID- 15504991
TI  - Continuous subcutaneous insulin infusion versus multiple daily injections: the
      impact of baseline A1c.
AB  - OBJECTIVE: Rapid-acting insulin analogs (insulin lispro and insulin aspart) have
      emerged as the meal insulin of choice in both multiple daily insulin injection
      (MDII) therapy and continuous subcutaneous insulin infusion (CSII) for type 1
      diabetes. Thus, a comparison of efficacy between CSII and MDII should be
      undertaken only in studies that used rapid-acting analogs for both intensive
      regimens. RESEARCH DESIGN AND METHODS: We performed a pooled analysis of the
      randomized controlled trials that compared CSII and optimized MDII therapy using
      rapid-acting analogs in adults with type 1 diabetes. RESULTS: The three studies
      that met inclusion criteria provided data on 139 patients, representing 596
      patient-months for CSII and 529 patient-months for MDII. Mean age was 38.5 years,
      with duration of diabetes of 18.0 years. The studies differed significantly in
      mean baseline A1c (7.95, 8.20, and 9.27%). The pooled estimate of treatment
      effect comparing the percentage reduction in A1c by CSII with that by MDII (CSII 
      MDII) was 0.35% (95% CI -0.10 to 0.80, P = 0.08) using a random effect to
      account for heterogeneity between studies. Importantly, the interaction between
      baseline A1c and treatment modality emerged as an independent predictor of
      treatment effect (CSII - MDII) (P = 0.002). The relative benefit of CSII over
      MDII was found to increase with higher baseline A1c. A model derived from these
      data predicts that in a patient with a baseline A1c of 10%, CSII would reduce the
      A1c by an additional 0.65% compared with MDII. Conversely, there would be no A1c
      benefit of CSII compared with MDII if baseline A1c were 6.5%. There was no
      significant difference between CSII and MDII in the rate of hypoglycemic events.
      CONCLUSIONS: When using rapid-acting insulin analogs in CSII and MDII regimens in
      adult patients with type 1 diabetes, insulin pump therapy is associated with
      better glycemic control, particularly in those individuals with higher baseline
      A1c. Thus, CSII emerges as an important modality for implementing intensive
      therapy and may be uniquely advantageous in patients with poor glycemic control.

PMID- 15504992
TI  - Induction of long-term glycemic control in newly diagnosed type 2 diabetic
      patients is associated with improvement of beta-cell function.
AB  - OBJECTIVE: To investigate whether long-term optimal glycemic control can be
      achieved without medication by transient continuous subcutaneous insulin infusion
      (CSII) and the possible mechanisms responsible for this remission. RESEARCH
      DESIGN AND METHODS: Newly diagnosed type 2 diabetic patients (n = 138, fasting
      glucose >11.1mmol/l) were hospitalized and treated with CSII for 2 weeks.
      Intravenous glucose tolerance tests (IVGTTs) were performed, and blood glucose,
      HbA(1c), lipid profiles, proinsulin, insulin, and C-peptide were measured before
      and after CSII. Patients were followed longitudinally on diet alone after
      withdrawal of insulin. RESULTS: Optimal glycemic control was achieved within 6.3
      +/- 3.9 days by CSII in 126 patients. The remission rates (percentages
      maintaining near euglycemia) at the third, sixth, twelfth, and twenty-fourth
      month were 72.6, 67.0, 47.1, and 42.3%, respectively. Patients who maintained
      glycemic control >12 months (remission group) had greater recovery of beta-cell
      function than those who did not (nonremission group) when assessed immediately
      after CSII. Homeostasis model assessment of beta-cell function (HOMA-B) and the
      area under the curve (AUC) of insulin during IVGTT were higher in the remission
      group (145.4 +/- 89.6 vs. 78.5 +/- 68.5, P = 0.002, and 1,423.4 +/- 523.2 vs.
      1,159.5 +/- 476.8 pmol x l(-1) x min(-1), P = 0.044). Change in acute insulin
      response was also greater in the remission group than that in the nonremission
      group (621.8 +/- 430.4 vs. 387.3 +/- 428.8 pmol x l(-1) x min(-1), P = 0.033).
      CONCLUSIONS: Short-term intensive insulin therapy can induce long-term glycemic
      control in newly diagnosed type 2 diabetic patients with severe hyperglycemia.
      The improvement of beta-cell function, especially the restoration of first-phase
      insulin secretion, could be responsible for the remission.

PMID- 15504993
TI  - Physical activity and television viewing in relation to risk of undiagnosed
      abnormal glucose metabolism in adults.
AB  - OBJECTIVE: The goal of this study was to assess the associations of physical
      activity time and television (TV) time with risk of "undiagnosed" abnormal
      glucose metabolism in Australian adults. RESEARCH DESIGN AND METHODS: This
      population-based cross-sectional study using a stratified cluster design
      involving 42 randomly selected Census Collector Districts across Australia
      included 8,299 adults aged 25 years or older who were free from new type 2
      diabetes and self-reported ischemic disease and did not take lipid-lowering or
      antihypertensive drugs. Abnormal glucose metabolism (impaired fasting glycemia
      [IFG], impaired glucose tolerance [IGT], or new type 2 diabetes) was based on an
      oral glucose tolerance test. Self-reported physical activity time and TV time
      (previous week) were assessed using interviewer-administered questionnaires.
      RESULTS: After adjustment for known confounders and TV time, the odds ratio (OR)
      of having abnormal glucose metabolism was 0.62 (95% CI 0.41-0.96) in men and 0.71
      (0.50-1.00) in women for those engaged in physical activity >or=2.5 h/week
      compared with those who were sedentary (0 h/week). The ORs of having abnormal
      glucose metabolism were 1.16 (0.79-1.70) in men and 1.49 (1.12-1.99) in women who
      watched TV >14 h/week compared with those who watched <or=7.0 h/week. Higher TV
      viewing (>14 h/week) was also associated with an increased risk of new type 2
      diabetes in men and women and IGT in women compared with those watching <14
      h/week. Total physical activity of >or=2.5 h/week was associated with a reduced
      risk of IFG, IGT, and new type 2 diabetes in both sexes; however, only the
      association with IGT in women was statistically significant. CONCLUSIONS: These
      findings suggest a protective effect of physical activity and a deleterious
      effect of TV time on the risk of abnormal glucose metabolism in adults.
      Population strategies to reduce risk of abnormal glucose metabolism should focus
      on reducing sedentary behaviors such as TV time, as well as increasing physical
      activity.

PMID- 15504994
TI  - The Blood Glucose Monitoring Communication questionnaire: an instrument to
      measure affect specific to blood glucose monitoring.
AB  - OBJECTIVE: The aim of this study was to present the psychometric properties of a
      new tool for evaluating affective response to blood glucose monitoring (BGM) in
      youths with type 1 diabetes and their parents. RESEARCH DESIGN AND METHODS: Study
      participants included 153 youths with type 1 diabetes and their parents. Each
      youth and parent completed the Blood Glucose Monitoring Communication (BGMC)
      questionnaire, Diabetes Family Conflict Scale, and Pediatric Quality of Life
      Inventory. Statistical analyses evaluated the psychometric properties of the BGMC
      questionnaires and their association with glycemic outcomes. RESULTS: Youth and
      parent BGMC questionnaires had acceptable internal consistency (youth, alpha =
      0.77; parent, alpha = 0.82) and 1-year test-retest reliability (youth, r = 0.60;
      parent, r = 0.80). Higher BGMC questionnaire scores (indicating more negative
      affect) showed a strong association with higher levels of diabetes-specific
      family conflict (youth, r = 0.33; parent, r = 0.44) and poorer health-related
      psychosocial quality of life (youth, r = -0.50; parent, r = -0.42). Higher BGMC
      questionnaire scores were also associated with poorer glycemic control (youth, r
      = 0.28; parent, r = 0.20), even when the effects of diabetes-specific family
      conflict and psychosocial quality of life were controlled. Youths with BGMC
      questionnaire scores in the upper quartile had A1c values 1 percentage point
      higher (9.1%) than youths with scores in the lowest quartile (8.0%). CONCLUSIONS:
      The BGMC questionnaires have strong psychometric properties and are convenient
      measures of affect specific to BGM. Further, BGM affect is associated with
      glycemic outcomes and may provide a unique contribution to factors associated
      with glycemic control in youths.

PMID- 15504995
TI  - Direct health care costs of diabetic patients in Spain.
AB  - OBJECTIVE: The goal of this study was to estimate the health care resources spent
      by type 1 and type 2 diabetic patients in Spain during the year 2002. RESEARCH
      DESIGN AND METHODS: This is a cost-of-illness study focusing on direct health
      care costs estimated from primary and secondary sources of information. A
      prevalence of diabetes ranging from 5 to 6% of the adult population was
      determined. Total cost is composed of six items: insulin and oral hypoglycemic
      agents, other drugs, disposable and consumable goods (glucose test strips,
      needles, and syringes), hospitalization, primary care visits, and visits to
      endocrinologists and dialysis. RESULTS: The estimated direct cost of diabetes in
      2002 ranges from 2.4 to 2.67 billion euro. Hospital costs were the most (933
      million euro), followed by noninsulin, nonhypoglycemic agent drugs (777-932
      million euro). Much lower are the costs of insulin and oral hypoglycemic agents
      (311 million euro), primary care visits (181-272 million euro), specialized
      visits (127-145 million euro), and disposable elements (70-81 million euro).
      Expenditures for all drugs and consumable goods ranged between 1.16 and 1.3
      billion euro, representing 48-49% of total cost, which is 15% higher than
      hospital costs. CONCLUSIONS: The direct health care costs of diabetic patients
      are high (6.3-7.4% of total National Health System expenditure). Their average
      annual cost is 1,290-1,476 euro. For individuals without diabetes, the average
      annual cost is 865 euro.

PMID- 15504996
TI  - Efficacy and safety of inhaled insulin (Exubera) compared with subcutaneous
      insulin therapy in patients with type 1 diabetes: results of a 6-month,
      randomized, comparative trial.
AB  - OBJECTIVE: The aim of this study was to determine whether premeal pulmonary
      delivery of rapid-acting, dry-powder insulin (Exubera) plus Ultralente could
      provide glycemic control comparable to a conventional insulin regimen in type 1
      diabetes. RESEARCH DESIGN AND METHODS: Three hundred thirty-five subjects were
      randomly assigned to receive either premeal inhaled insulin plus bedtime
      Ultralente or two to three injections of regular and NPH insulin for 24 weeks.
      The primary end point was a change in HbA(1c). RESULTS: Mean decreases in HbA(1c)
      values were comparable for inhaled (8.1-7.9%) and conventional groups (8.1-7.7%)
      (adjusted treatment group difference 0.16% [95% CI -0.01 to 0.32]). There were
      greater reductions for inhaled versus conventional regimen in fasting and
      postprandial plasma glucose (adjusted mean change differences -25.17 and -30.28
      mg/dl, respectively [95% CI -43.39 to -6.95 and -54.58 to -5.97, respectively]).
      Hypoglycemia (events/subject month) was lower for the inhaled (8.6) versus the
      conventional (9.0) group (risk ratio, 0.96 [95% CI 0.93-0.99]). In subjects
      receiving inhaled insulin, increased insulin antibody levels were observed, but
      there were no associated clinical or laboratory changes. Adverse events were
      comparable between groups. Mild to moderate cough was more frequent in the
      inhaled insulin group (27 vs. 5%) but decreased during the treatment. Pulmonary
      function tests were not different between the groups except for a greater
      decrease in carbon monoxide diffusing capacity in the inhaled insulin group.
      Treatment satisfaction was greater in the inhaled than in the conventional group.
      CONCLUSIONS: Inhaled insulin is effective, well tolerated, and well accepted in
      patients with type 1 diabetes and provides glycemic control comparable to that
      with a conventional insulin regimen.

PMID- 15504997
TI  - Effects of exenatide (exendin-4) on glycemic control over 30 weeks in
      sulfonylurea-treated patients with type 2 diabetes.
AB  - OBJECTIVE: This study evaluated the ability of the incretin mimetic exenatide
      (exendin-4) to improve glycemic control in patients with type 2 diabetes failing
      maximally effective doses of a sulfonylurea as monotherapy. RESEARCH DESIGN AND
      METHODS: This was a triple-blind, placebo-controlled, 30-week study conducted at
      101 sites in the U.S. After a 4-week, single-blind, placebo lead-in period, 377
      subjects were randomized (60% men, age 55 +/- 11 years, BMI 33 +/- 6 kg/m(2),
      HbA(1c) 8.6 +/- 1.2% [+/-SD]) and began 4 weeks at 5 microg subcutaneous
      exenatide twice daily (before breakfast and dinner; arms A and B) or placebo.
      Subsequently, subjects in arm B were escalated to 10 microg b.i.d. exenatide. All
      subjects continued sulfonylurea therapy. RESULTS: At week 30, HbA(1c) changes
      from baseline were -0.86 +/- 0.11, -0.46 +/- 0.12, and 0.12 +/- 0.09% (+/-SE) in
      the 10-microg, 5-microg, and placebo arms, respectively (adjusted P < 0.001). Of
      evaluable subjects with baseline HbA(1c) > 7% (n = 237), 41% (10 microg), 33% (5
      microg), and 9% (placebo) achieved HbA(1c) <or= 7% (P < 0.001). Fasting plasma
      glucose concentrations decreased in the 10-microg arm compared with placebo (P <
      0.05). Subjects in the exenatide arms had dose-dependent progressive weight loss,
      with an end-of-study loss in the 10-microg exenatide arm of -1.6 +/- 0.3 kg from
      baseline (P < 0.05 vs. placebo). The most frequent adverse events were generally
      mild or moderate and gastrointestinal in nature. No severe hypoglycemia was
      observed. CONCLUSIONS: Exenatide significantly reduced HbA(1c) in patients with
      type 2 diabetes failing maximally effective doses of a sulfonylurea. Exenatide
      was generally well tolerated and was associated with weight loss.

PMID- 15504998
TI  - Explanations for the high risk of diabetes-related amputation in a Caribbean
      population of black african descent and potential for prevention.
AB  - OBJECTIVE: Diabetes-related lower-extremity amputation (LEA) rates are elevated
      in blacks compared with whites in the U.S., but are lower in African Caribbeans
      in the U.K., whereas anecdotal reports suggest high rates in the Caribbean. We
      aimed to establish the incidence and risk factors for diabetes-related LEA in a
      Caribbean population. RESEARCH DESIGN AND METHODS: We conducted an incident and
      prospective case-control study of case patients (individuals with diabetes having
      a LEA) and community-based control subjects (individuals with diabetes without a
      LEA) in Barbados, West Indies. Participants completed an interview and
      examination of risk factors for amputation, including footwear use. RESULTS: The
      overall 1-year incidence of LEA (n = 223) was 173 per 10(5) population and 936
      per 10(5) population with diabetes (557 per 10(5) for minor amputation and 379
      per 10(5) for major amputation). Women had higher amputation rates than those
      reported in the Global Lower Extremity Amputation Study, apart from the U.S.
      Navajo population. Independent risk factors for all diabetes-related LEAs were
      poor footwear (odds ratio [OR] 2.71 [95% CI 1.23-5.97]), elevated GHb (1.40 per
      percent increase [1.26-1.57]), peripheral neuropathy (1.05 per volt increase
      [1.03-1.08]), and peripheral vascular disease. CONCLUSIONS: Diabetes LEA rates in
      Barbados are among the highest in the world. Inadequate footwear independently
      tripled amputation risk. Education of professionals and patients, particularly
      about footwear and foot care, coupled with improved diabetes clinical care, is
      key to reducing amputation risk in this population.

PMID- 15504999
TI  - Home monitoring of foot skin temperatures to prevent ulceration.
AB  - OBJECTIVE: To evaluate the effectiveness of at-home infrared temperature
      monitoring as a preventative tool in individuals at high risk for diabetes
      related lower-extremity ulceration and amputation. RESEARCH DESIGN AND METHODS:
      Eighty-five patients who fit diabetic foot risk category 2 or 3 (neuropathy and
      foot deformity or previous history of ulceration or partial foot amputation) were
      randomized into a standard therapy group (n = 41) or an enhanced therapy group (n
      = 44). Standard therapy consisted of therapeutic footwear, diabetic foot
      education, and regular foot evaluation by a podiatrist. Enhanced therapy included
      the addition of a handheld infrared skin thermometer to measure temperatures on
      the sole of the foot in the morning and evening. Elevated temperatures (>4
      degrees F compared with the opposite foot) were considered to be "at risk" of
      ulceration due to inflammation at the site of measurement. When foot temperatures
      were elevated, subjects were instructed to reduce their activity and contact the
      study nurse. Study subjects were followed for 6 months. RESULTS: The enhanced
      therapy group had significantly fewer diabetic foot complications (enhanced
      therapy group 2% vs. standard therapy group 20%, P = 0.01, odds ratio 10.3, 95%
      CI 1.2-85.3). There were seven ulcers and two Charcot fractures among standard
      therapy patients and one ulcer in the enhanced therapy group. CONCLUSIONS: These
      results suggest that at-home patient self-monitoring with daily foot temperatures
      may be an effective adjunctive tool to prevent foot complications in individuals
      at high risk for lower-extremity ulceration and amputation.

PMID- 15505000
TI  - Renal impairment associated with diabetes in the elderly.
AB  - OBJECTIVE: To characterize renal impairment associated with diabetes in older
      adults by serum markers of glomerular filtration rate and microalbuminuria tests.
      RESEARCH DESIGN AND METHODS: The study population consisted of 187 diabetic and
      1,073 nondiabetic subjects (age range 64-100 years) participating in a cross
      sectional, population-based survey in southwestern Finland. Renal function was
      estimated by serum cystatin C (Cys C), serum creatinine (Cr), and the urinary
      albumin-to-creatinine ratio, and determinants of elevated levels were assessed by
      multivariate analysis. RESULTS: Diabetes, compared to hypertension, was a more
      powerful determinant of elevated Cys C and Cr levels in the very old (age >or=80
      years), whereas the impact of hypertension was more pronounced in the younger
      group (age <80 years). The prevalence of microalbuminuria among diabetic subjects
      was 29.7%, and 15% had elevated Cr levels, whereas the prevalence of elevated Cys
      C levels varied considerably depending on whether adult or age-adjusted reference
      limits were used (64.7 vs. 21.4%). In 64.1% of diabetic subjects with elevated
      Cys C levels based on age-adjusted reference limits and in 48.2% of subjects with
      elevated Cr levels, microalbuminuria was absent. CONCLUSIONS: The impact of
      diabetes on renal impairment changes with increasing age. Serum markers of
      glomerular filtration rate and microalbuminuria identify renal impairment in
      different segments of the diabetic population, indicating that serum markers as
      well as microalbuminuria tests should be used in screening for nephropathy in
      diabetic older people. The appropriate reference limit for Cys C in geriatric
      clinical practice must be defined by further research.

PMID- 15505001
TI  - Preventative effects of rosiglitazone on restenosis after coronary stent
      implantation in patients with type 2 diabetes.
AB  - OBJECTIVE: Despite the popularity of coronary stenting in coronary artery disease
      (CAD), restenosis remains a challenging clinical problem. This study evaluated
      the efficacy of rosiglitazone for preventing in-stent restenosis in type 2
      diabetic patients. RESEARCH DESIGN AND METHODS: We conducted a prospective,
      randomized, case-controlled trial involving 95 diabetic patients with CAD who
      were randomly assigned to either the control or rosiglitazone group (48 and 47
      patients, respectively). Quantitative coronary angiography (QCA) was performed at
      study entry and again at 6-month follow-up. The primary end point was the
      restenosis rate, which was determined by QCA. RESULTS: Eighty-three patients (45
      patients with 55 lesions in the control group and 38 patients with 51 lesions in
      the rosiglitazone group) completed follow-up angiography. Rosiglitazone treatment
      for 6 months reduced fasting insulin concentration. The high-sensitivity C
      reactive protein concentration was significantly reduced in the rosiglitazone
      group compared with that in the control group (from 2.92 +/- 1.98 to 0.62 +/-
      0.44 mg/l, P < 0.001 vs. from 2.01 +/- 1.33 to 1.79 +/- 1.22 mg/l, P = NS).
      However, the baseline and follow-up glucose and lipid concentrations were not
      different between two groups. The rate of in-stent restenosis was significantly
      reduced in the rosiglitazone group compared with the control group (for stent
      lesions: 17.6 vs. 38.2%, P = 0.030). The rosiglitazone group had a significantly
      lower degree of diameter stenosis (23.0 +/- 23.4% vs. 40.9 +/- 31.9%, P = 0.004)
      compared with the control group. CONCLUSIONS: We demonstrated that treatment with
      rosiglitazone significantly reduces in-stent restenosis in diabetic patients with
      CAD who underwent coronary stent implantation.

PMID- 15505002
TI  - Different patterns of insulin resistance in relatives of type 1 diabetic patients
      with retinopathy or nephropathy: the Genesis France-Belgium Study.
AB  - OBJECTIVE: Insulin resistance may be a risk factor for diabetic microangiopathy,
      which may have a familial component. We carried out a family-based study to
      determine which components of the insulin resistance syndrome are associated with
      diabetic retinopathy and nephropathy in type 1 diabetes. RESEARCH DESIGN AND
      METHODS: The Genesis France-Belgium Study is a multicenter binational study
      designed to investigate the genetic factors involved in the microvascular
      complications of type 1 diabetes using a family-based design. Probands were type
      1 diabetic patients with diabetic retinopathy (classified as background,
      preproliferative, or proliferative) and possibly diabetic nephropathy (absent,
      incipient, established, or advanced). The insulin resistance score of their first
      degree relatives was calculated according to their BMI and history of arterial
      hypertension, lipid disorders, and type 2 diabetes. RESULTS: The insulin
      resistance score of relatives was positively correlated with the albumin
      excretion rate (P = 0.0009) and fasting plasma glucose (P = 0.0003) and HbA(1c)
      (P < 0.0001) concentrations. This score was higher in the relatives of probands
      with than in those without diabetic nephropathy (P = 0.0370). Similarly, it was
      higher in relatives of subjects with proliferative diabetic retinopathy than in
      those of probands without, even after controlling for subjects with versus
      without diabetic nephropathy (P = 0.0379). However, the components of the insulin
      resistance score in relatives differed according to the severity of diabetic
      retinopathy or nephropathy in the probands. Obesity and history of arterial
      hypertension were most common in relatives of probands with proliferative
      diabetic retinopathy, whereas obesity and history of lipid disorders were most
      common in the relatives of probands with diabetic nephropathy. CONCLUSIONS:
      Familial insulin resistance segregates with diabetic complications: lipid
      disorders and obesity segregate with diabetic nephropathy, whereas arterial
      hypertension and obesity segregate with diabetic retinopathy.

PMID- 15505003
TI  - Diabetes is the main factor accounting for the high ferritin levels detected in
      chronic hepatitis C virus infection.
AB  - OBJECTIVE: A high prevalence of diabetes has been reported in patients with
      hepatitis C virus (HCV) infection. Both diabetes and HCV infection are associated
      with high serum ferritin levels. Although HCV infection could be the main factor
      responsible for the high ferritin levels, it is also possible that diabetes
      rather than HCV infection might be a major contributor to the high ferritin
      levels observed in patients with HCV infection. The aim of this study was to
      investigate the contribution of diabetes to the high ferritin levels observed in
      HCV-infected patients with chronic hepatitis. RESEARCH DESIGN AND METHODS: A
      total of 634 noncirrhotic individuals were prospectively recruited at a
      university hospital. According to the HCV antibody status and the presence of
      diabetes, the subjects were divided into four groups: group A (anti-HCV-positive
      diabetic patients, n = 53), group B (anti-HCV-negative diabetic patients, n =
      242), group C (anti-HCV-positive nondiabetic patients, n = 191), and group D
      (anti-HCV-negative nondiabetic control subjects, n = 148). Multiple regression
      analyses were used to explore the variables independently related to ferritin
      levels. RESULTS: Serum ferritin levels in group A were significantly higher than
      in the other groups (A > B, P < 0.01; A > C, P < 0.001; A > D, P < 0.001).
      Ferritin levels were higher in group B than in group D (P = 0.001). However,
      group C has ferritin values similar to those of group D. In multivariate
      analyses, diabetes but not HCV infection was independently related to serum
      ferritin concentrations. CONCLUSIONS: Diabetes rather than HCV infection itself
      is the main factor associated with the increased ferritin levels detected in
      patients with HCV infection. Therefore, the presence of diabetes should be taken
      into account when iron metabolism is evaluated in HCV-infected patients.

PMID- 15505004
TI  - Does the metabolic syndrome improve identification of individuals at risk of type
      2 diabetes and/or cardiovascular disease?
AB  - OBJECTIVE: The metabolic syndrome has been promoted as a method for identifying
      high-risk individuals for type 2 diabetes and cardiovascular disease (CVD). We
      therefore sought to compare this syndrome, as defined by the National Cholesterol
      Education Program, to the Diabetes Predicting Model and the Framingham Risk Score
      as predictors of type 2 diabetes and CVD, respectively. RESEARCH DESIGN AND
      METHODS: A population-based sample of 1,709 initially nondiabetic San Antonio
      Heart Study (SAHS) participants were followed for 7.5 years, 195 of whom
      developed type 2 diabetes. Over the same time interval, 156 of 2,570 SAHS
      participants experienced a cardiovascular event. A population-based sample of
      1,353 initially nondiabetic Mexico City Diabetes Study (MCDS) participants were
      followed for 6.5 years, 125 of whom developed type 2 diabetes. Baseline
      measurements included medical history, age, sex, ethnicity, smoking status, BMI,
      blood pressure, fasting and 2-h plasma glucose levels, and fasting serum total
      and HDL cholesterol and triglycerides. RESULTS: The sensitivities for predicting
      diabetes with the metabolic syndrome were 66.2 and 62.4% in the SAHS and the
      MCDS, respectively, and the false-positive rates were 27.8 and 38.7%,
      respectively. The sensitivity and false-positive rates for predicting CVD with
      the metabolic syndrome in the SAHS were 67.3 and 34.2%, respectively. At
      corresponding false-positive rates, the two predicting models had significantly
      higher sensitivities and, at corresponding sensitivities, significantly lower
      false-positive rates than the metabolic syndrome for both end points. Combining
      the metabolic syndrome with either predicting model did not improve the
      prediction of either end point. CONCLUSIONS: The metabolic syndrome is inferior
      to established predicting models for either type 2 diabetes or CVD.

PMID- 15505005
TI  - The impact of abnormalities in IGF and inflammatory systems on the metabolic
      syndrome.
AB  - OBJECTIVE: Low plasma levels of IGF-I, particularly when coupled with low levels
      of the potentially inhibitory IGF binding protein (IGFBP)-1 and higher levels of
      C-reactive protein (CRP), have been implicated in the pathogenesis of metabolic
      syndrome X and cardiovascular disease. We report the relative contributions of
      IGFBP-1 and CRP to the occurrence of the metabolic syndrome in a healthy
      population cohort to establish the extent to which these factors may contribute
      to subsequent risk of cardiovascular disease. RESEARCH DESIGN AND METHODS: The
      volunteers in the study were all participants in the Ely study, a continuing
      population-based cohort in Ely, Cambridgeshire, U.K. Of 839 individuals studied,
      154 (18.4%) fulfilled criteria for the metabolic syndrome. RESULTS: Subjects with
      the metabolic syndrome had lower IGFBP-1 (14.4 microg/l [95% CI 12.9-16.0] vs.
      25.4 [24.1-26.7], P < 0.001) and higher CRP (1.9 mg/l [1.6-2.2] vs. 1.0 [0.9
      1.1], P < 0.001). Logistic regression, adjusted for age, sex, fasting insulin,
      and IGF-I, demonstrated a striking 14-fold increased risk for the metabolic
      syndrome (odds ratio 14.1 [4.1-48.4], P < 0.001) in individuals with a CRP value
      in the highest tertile and IGFBP-1 levels below the median. CONCLUSIONS: The
      combination of a high CRP concentration coupled with a low IGFBP-1 results in a
      dramatic increase in an individual's risk of having the metabolic syndrome.
      Further elucidation of the biological processes linking the IGF and inflammatory
      systems may allow the identification of novel therapeutic targets for
      cardiovascular risk reduction.

PMID- 15505006
TI  - Metabolic syndrome as a predictor of all-cause and cardiovascular mortality in
      type 2 diabetes: the Casale Monferrato Study.
AB  - OBJECTIVE: The aim of this study was to assess in an 11-year survival follow-up
      of a population-based cohort of type 2 diabetes the predictive role of World
      Health Organization-defined metabolic syndrome, independent of conventional
      cardiovascular risk factors. RESEARCH DESIGN AND METHODS: During the follow-up
      (1991-2001), 1,565 patients were regularly examined with centralized measurements
      of HbA(1c). The independent role of the metabolic syndrome as a predictor of all
      cause and cardiovascular mortality was assessed with multivariate Cox
      proportional hazards modeling. RESULTS: At baseline, the prevalence of the
      metabolic syndrome was 75.6% (95% CI 73.6-77.9). Results are based on 685 deaths
      (520 with the metabolic syndrome and 165 without it) in 10,890.2 person-years of
      observations. With respect to subjects without the metabolic syndrome, those with
      the metabolic syndrome had a similar hazard ratio (HR) of cardiovascular
      mortality after adjustment for age, sex, smoking, total cholesterol level, and
      coronary heart disease. In contrast, relative to subjects with diabetes only, the
      HR of subjects with only one component of the syndrome was 2.92 (1.16-7.33),
      independent of other risk factors. CONCLUSIONS: We found that 1) the prevalence
      of the metabolic syndrome in a population-based cohort of type 2 diabetes is high
      (75.6%); 2) the metabolic syndrome is not a predictor of 11-year all-cause and
      cardiovascular mortality; and 3) more than twofold higher cardiovascular risk,
      independent of conventional risk factors, is evident in diabetic subjects with
      only one component of the syndrome compared with those with diabetes only.
      Categorizing type 2 diabetic subjects as having or not having the metabolic
      syndrome does not provide further prediction compared with the knowledge of its
      single components.

PMID- 15505007
TI  - IDDM1 and multiple family history of type 1 diabetes combine to identify neonates
      at high risk for type 1 diabetes.
AB  - OBJECTIVE: Children of affected probands are at increased risk for type 1
      diabetes. The objective of this study was to determine and stratify the risk for
      islet autoimmunity and childhood diabetes in newborn offspring of affected
      parents using family history and HLA genetic markers. RESEARCH DESIGN AND
      METHODS: Antibodies to islet autoantigens were measured at ages 9 months, 2
      years, 5 years, and 8 years in 1,610 offspring of parents with type 1 diabetes
      participating in the German BABYDIAB study. HLA DR and DQ genetic typing was
      performed. Family history of type 1 diabetes was obtained from questionnaires.
      RESULTS: Extensive family history of type 1 diabetes and HLA DR/DQ genotyping
      were associated with islet autoantibody and diabetes risks. Significant
      contributions to the child's risk for developing islet autoantibodies and type 1
      diabetes were conferred by a multiple first-degree family history of type 1
      diabetes (two parents or one parent and a sibling; adjusted hazard [HR] ratio,
      6.2 for multiple islet autoantibodies and 7.8 for type 1 diabetes), high-risk HLA
      genotypes (adjusted HR, 11 and 10.9), and moderate-risk HLA genotypes (adjusted
      HR, 6.3 and 4.3) in a multivariate analysis. Combining these factors stratified
      the risk for islet autoantibodies from 1 to 46% and for type 1 diabetes from 0 to
      19.5% by 5 years of age. CONCLUSIONS: Risk of childhood diabetes in affected
      families can be stratified using a combination of genetic and family history
      markers very early in life.

PMID- 15505008
TI  - Glycemic index and dietary fiber and the risk of type 2 diabetes.
AB  - OBJECTIVE: To examine associations between type 2 diabetes and fiber, glycemic
      load (GL), dietary glycemic index (GI), and fiber-rich foods. RESEARCH DESIGN AND
      METHODS: This was a prospective study of 36,787 men and women aged 40-69 years
      without diabetes. For all self-reported cases of diabetes at 4-year follow-up,
      confirmation of diagnosis was sought from medical practitioners. Case subjects
      were those who reported diabetes at follow-up and for whom there was no evidence
      that they did not have type 2 diabetes. Data were analyzed with logistic
      regression, adjusting for country of birth, physical activity, family history of
      diabetes, alcohol and energy intake, education, 5-year weight change, sex, and
      age. RESULTS: Follow-up was completed by 31,641 (86%) participants, and 365 cases
      were identified. The odds ratio (OR) for the highest quartile of white bread
      intake compared with the lowest was 1.37 (95% CI 1.04-1.81; P for trend = 0.001).
      Intakes of carbohydrate (OR per 200 g/day 0.58, 0.36-0.95), sugars (OR per 100
      g/day 0.61, 0.47-0.79), and magnesium (OR per 500 mg/day 0.62, 0.43-0.90) were
      inversely associated with incidence of diabetes, whereas intake of starch (OR per
      100 g/day 1.47, 1.06-2.05) and dietary GI (OR per 10 units 1.32, 1.05-1.66) were
      positively associated with diabetes. These relationships were attenuated after
      adjustment for BMI and waist-to-hip ratio. CONCLUSIONS: Reducing dietary GI while
      maintaining a high carbohydrate intake may reduce the risk of type 2 diabetes.
      One way to achieve this would be to substitute white bread with low-GI breads.

PMID- 15505009
TI  - Risk factors for the metabolic syndrome: the Coronary Artery Risk Development in
      Young Adults (CARDIA) study, 1985-2001.
AB  - OBJECTIVE: The aim of this study was to describe the association of the metabolic
      syndrome with demographic characteristics and to identify modifiable risk factors
      for development of the metabolic syndrome. RESEARCH DESIGN AND METHODS: Men and
      women (55%) aged 18-30 years from the Coronary Artery Risk Development in Young
      Adults (CARDIA) study without the metabolic syndrome at baseline (n = 4,192, 49%
      black) were followed-up from 1985 to 2001. Incident metabolic syndrome, defined
      according to the National Cholesterol Education Program Adult Treatment Panel III
      criteria, was ascertained 7, 10, and 15 years after baseline. Risk factors were
      measured via clinical examination and standardized questionnaires. RESULTS: The
      age-adjusted rate of metabolic syndrome was 10 per 1,000 person-years (n = 575).
      Metabolic syndrome risk increased with age and was higher among black
      participants and those with less than a high school education. Higher baseline
      BMI, no alcohol intake (versus one to three drinks per day), higher intake of
      dietary carbohydrates, and lower intake of crude fiber were each associated with
      an increased risk for the metabolic syndrome (relative risk [RR] ranging from 1.3
      to 1.9), and physical activity was protective (RR 0.84 [95% CI 0.76-0.92]). In
      models adjusting simultaneously for all factors, black participants and women
      were less likely to develop metabolic syndrome. Risk for metabolic syndrome
      increased 23% (20-27%) per 4.5 kg (10 lb) of weight gained, whereas regular
      physical activity over time versus low activity was protective (RR 0.49 [0.34
      0.70]). CONCLUSIONS: BMI and weight gain are important risk factors for the
      metabolic syndrome. Regular physical activity may counter this risk.

PMID- 15505011
TI  - Declining mortality rate among people with diabetes in North Dakota, 1997-2002.

PMID- 15505010
TI  - Postabsorptive and insulin-stimulated energy homeostasis and leucine turnover in
      offspring of type 2 diabetic patients.
AB  - OBJECTIVE: This study was performed to ascertain whether insulin resistance with
      respect to protein metabolism is an additional primary metabolic abnormality
      affecting insulin-resistant offspring of type 2 diabetic parents, along with
      insulin resistance with respect to glucose and lipid metabolism. RESEARCH DESIGN
      AND METHODS: We studied 18 young, nonobese offspring of type 2 diabetic parents
      and 27 healthy matched (by means of dual-energy X-ray absorption) individuals
      with the bolus plus continuous infusion of [6,6-(2)H(2)]glucose and [1
      (13)C]leucine in combination with the insulin clamp (40 mU x m(-2) x min(-1)).
      RESULTS: Fasting plasma leucine, phenylalanine, alanine, and glutamine
      concentrations, as well as the glucose and leucine turnover (reciprocal pool
      model: 155 +/- 10 vs. 165 +/- 5 micromol x kg lean body mass(-1) x h(-1) in
      offspring of type 2 diabetic patients and healthy matched individuals,
      respectively), were also not different. During the clamp, glucose turnover rates
      were significantly reduced in offspring of type 2 diabetic patients (7.1 +/- 0.5)
      in comparison with healthy matched individuals (9.9 +/- 0.6 mg x kg lean body
      mass(-1) x min(-1); P < 0.01). Also, the suppression of leucine turnover was
      impaired in offspring of type 2 diabetic patients (12 +/- 1%) in comparison with
      healthy matched individuals (17 +/- 1%; P = 0.04) and correlated with the degree
      of the impairment of insulin-stimulated glucose metabolism (R(2) = 0.13; P =
      0.02). CONCLUSIONS: Nonobese, nondiabetic, insulin-resistant offspring of type 2
      diabetic patients were characterized by an impairment of insulin-dependent
      suppression of protein breakdown, which was proportional to the impairment of
      glucose metabolism. These results demonstrate that in humans, a primary in vivo
      impairment of insulin action affects glucose and fatty acid metabolism as
      previously shown and also protein/amino acid metabolism.

PMID- 15505012
TI  - Intrahepatic lipids are predicted by visceral adipose tissue mass in healthy
      subjects.

PMID- 15505013
TI  - Serum chelatable redox-active iron is an independent predictor of mortality after
      myocardial infarction in individuals with diabetes.

PMID- 15505014
TI  - Acute respiratory viral infections aggravate arterial endothelial dysfunction in
      children with type 1 diabetes.

PMID- 15505015
TI  - Right ventricular dysfunction in asymptomatic diabetic patients.

PMID- 15505016
TI  - Effects of mixing glargine and short-acting insulin analogs on glucose control.

PMID- 15505017
TI  - Role of chromium in human health and in diabetes.

PMID- 15505018
TI  - Use of aspirin to reduce risks of cardiovascular disease in patients with
      diabetes: clinical and research challenges.

PMID- 15505019
TI  - Diet and diabetes.

PMID- 15505020
TI  - Metabolic syndrome: in search of a clinical role.

PMID- 15505021
TI  - Decreasing restenosis following angioplasty: the potential of peroxisome
      proliferator-activated receptor gamma agonists.

PMID- 15505022
TI  - Effect of controlling hyperglycemia with diet on QT abnormalities in newly
      diagnosed patients with type 2 diabetes.

PMID- 15505023
TI  - The effect of vitamin E supplementation on cardiovascular risk in diabetic
      individuals with different haptoglobin phenotypes.

PMID- 15505024
TI  - Impact of metformin on glucose metabolism in nondiabetic, obese African
      Americans: a placebo-controlled, 24-month randomized study.

PMID- 15505025
TI  - Elevated C-reactive protein levels do not correspond to autoimmunity in type 1
      diabetes.

PMID- 15505026
TI  - Orlistat augments postprandial increases in glucagon-like peptide-1 in obese type
      2 diabetic patients: response to Damci et al.

PMID- 15505028
TI  - Interaction of lumican with aggrecan in the aging human sclera.
AB  - PURPOSE: Lumican is a keratan sulfate proteoglycan originally identified in
      cornea, but present in a variety of connective tissues where it presumably
      regulates collagen fibril formation and organization. The present study was
      designed to describe the chemical nature of lumican core protein in the aging
      human sclera. METHODS: Western blot analyses, immunohistochemistry, and
      immunoaffinity chromatography were used to detect and purify the lumican core
      protein from tissue extracts from human donors 6 to 89 years of age. Treatment of
      lumican with chondroitinase ABC, keratanase-I and -II, and/or endo-beta
      galactosidase was used to determine the degree of glycosylation of the lumican
      core protein. RESULTS: Lumican was present in the human sclera as a 70- to 80-kDa
      core protein with short unsulfated lactosaminoglycan side chains. In addition, on
      Western blots, a larger >200-kDa species was apparent that was immunologically
      related to lumican. This high-molecular-weight material increased in scleral
      extracts with increasing age. The complex was most abundant in unreduced samples,
      and approximately two thirds of the 70- to 80-kDa lumican core protein was
      released from the complex on reduction of the scleral extract. Further
      characterization of the >200-kDa lumican-immunopurified complex indicated that
      aggrecan (the cartilage proteoglycan) was covalently associated with lumican.
      CONCLUSIONS: Reducible and nonreducible lumican-aggrecan interactions occur in
      the scleral extracellular matrix and result in the formation of high-molecular
      weight complexes that increase with age. These results represent the first report
      demonstrating lumican-aggrecan interactions and suggest they may play a role in
      age-related scleral extracellular matrix changes.

PMID- 15505029
TI  - Identification of RDH10, an All-trans Retinol Dehydrogenase, in Retinal Muller
      Cells.
AB  - PURPOSE: To investigate the expression of RDH10, an all-trans retinol
      dehydrogenase identified in the retinal pigment epithelium (RPE), in retinal
      Muller cells. METHODS: The RDH10 protein levels in mouse eyecups and bovine
      tissues were examined by Western blot analysis using a polyclonal antibody
      against RDH10. The cellular localization in the retina was determined by
      immunohistochemistry. Expression of RDH10 in rMC-1, a cell line derived from rat
      Muller cells, was determined by RT-PCR and Western blot analysis. All-trans
      retinol dehydrogenase activity assays were performed using lysates from rMC-1
      cells. The generation of all-trans retinal from tritiated all-trans retinol was
      analyzed by HPLC. RESULTS: RDH10, retinal G protein-coupled receptor (RGR), and
      RPE65 all had higher expression levels in the eyecups of BALB/c than in C57Bl/6
      mice. In addition to the RPE, RDH10 was also detected at lower levels in the
      retina and liver. Immunohistochemistry showed that RDH10 was localized in Muller
      cells in retinal sections. RDH10 was detected in rMC-1 cells, at both the RNA and
      protein levels. The rat RDH10 cDNA containing the full-length coding region was
      cloned from rMC-1 cells. The rat RDH10 cDNA encodes a protein of 341 amino acids
      and shares 99% sequence identity with human, bovine, and mouse RDH10 at the amino
      acid level. In rMC-1 cells, all-trans retinol dehydrogenase activity was detected
      in the microsomal fraction. NADP was shown to be the preferred cofactor, which is
      identical with the cofactor preference of the recombinant RDH10. CONCLUSIONS:
      RDH10 was expressed in retinal Muller cells, in addition to the RPE. RDH10
      generates all-trans retinal, which is the substrate for the photoisomerase RGR in
      Muller cells.

PMID- 15505030
TI  - A novel mutation (I143NT) in guanylate cyclase-activating protein 1 (GCAP1)
      associated with autosomal dominant cone degeneration.
AB  - PURPOSE: To identify pathogenic mutations in the guanylate cyclase-activating
      protein 1 (GCAP1) and GCAP2 genes and to characterize the biochemical effect of
      mutation on guanylate cyclase (GC) stimulation. METHODS: The GCAP1 and GCAP2
      genes were screened by direct sequencing for mutations in 216 patients and 421
      patients, respectively, with various hereditary retinal diseases. A mutation in
      GCAP1 segregating with autosomal dominant cone degeneration was further evaluated
      biochemically by employing recombinant proteins, immunoblotting, Ca2+-dependent
      stimulation of GC, fluorescence emission spectra, and limited proteolysis in the
      absence and presence of Ca2+. RESULTS: A novel GCAP1 mutation, I143NT
      (substitution of Ile at codon 143 by Asn and Thr), affecting the EF4 Ca2+-binding
      loop, was identified in a heterozygote father and son with autosomal dominant
      cone degeneration. Both patients had much greater loss of cone function versus
      rod function; previous histopathologic evaluation of the father's eyes at autopsy
      (age 75 years) showed no foveal cones but a few, scattered cones remaining in the
      peripheral retina. Biochemical analysis showed that the GCAP1-I143NT mutant
      adopted a conformation susceptible to proteolysis, and the mutant inhibited GC
      only partially at high Ca2+ concentrations. Individual patients with atypical or
      recessive retinitis pigmentosa (RP) had additional heterozygous GCAP1-T114I and
      GCAP2 gene changes (V85M and F150C) of unknown pathogenicity. CONCLUSIONS: A
      novel GCAP1 mutation, I143NT, caused a form of autosomal dominant cone
      degeneration that destroys foveal cones by mid-life but spares some cones in the
      peripheral retina up to 75 years. Properties of the GCAP1-I143NT mutant protein
      suggested that it is incompletely inactivated by high Ca2+ concentrations as
      should occur with dark adaptation. The continued activity of the mutant GCAP1
      likely results in higher-than-normal scotopic cGMP levels which may, in turn,
      account for the progressive loss of cones.

PMID- 15505031
TI  - Absence of SIX6 mutations in microphthalmia, anophthalmia, and coloboma.
AB  - PURPOSE: To investigate whether 173 patients with microphthalmia, anophthalmia,
      and coloboma have mutations in the eye-development gene SIX6. METHODS: The two
      exons of the SIX6 gene were amplified by PCR from patients' genomic DNA and
      directly sequenced to search for mutations. The PCR products of 75 patients were
      also analyzed by denaturing high-performance liquid chromatography (DHPLC).
      RESULTS: Six SIX6 polymorphisms were identified in the patient panel. Three of
      these polymorphisms change the encoded amino acid. However, all six polymorphisms
      were also identified in unaffected individuals. There was no statistically
      significant difference in genotypes between patients and control subjects.
      CONCLUSIONS: No evidence was found that SIX6 mutations underlie human congenital
      structural eye malformations.

PMID- 15505032
TI  - Deciphering the contribution of known cis-elements in the mouse cone arrestin
      gene to its cone-specific expression.
AB  - PURPOSE: Cone arrestin (CAR) is highly expressed in all cone photoreceptors of
      the retina and a subset of pinealocytes in the pineal gland. This study was
      initiated to examine the cis-elements responsible for the cell-specific
      expression pattern of CAR. METHODS: Mutagenesis and specific deletions of known
      cis-elements in the proximal promoter of the mouse CAR (mCAR) gene were
      introduced and analyzed in vitro and in vivo. A series of mCAR promoter
      luciferase reporter constructs were transiently transfected into COS-7 or Weri-Rb
      1 retinoblastoma cells and tested in in vitro promoter assays. Transgenic Xenopus
      laevis were created with deletional or mutated promoter fragments driving an
      enhanced green fluorescent protein (EGFP) reporter gene. The resultant EGFP
      expression pattern in the transgenic animals was analyzed by fluorescence
      microscopy and immunocytochemistry. RESULTS: A significant decrease in in vitro
      transcriptional activities was observed when the minimal 215-bp promoter fragment
      was mutated in each of the four cone-rod homeobox (CRX)-binding elements (CBEs)
      or in either of the two TATA-elements. The 215-bp mCAR proximal promoter drove
      EGFP expression to cone photoreceptors and pinealocytes in transgenic Xenopus
      laevis; however, the truncated 147-bp fragment drove expression to both cone and
      rod photoreceptors. Transgenic tadpoles carrying a single mutation in either the
      TATA-box, the TATA-element or the proximal CBE had undetectable EGFP expression
      in the retina. However, when one of the other three CBEs was mutated, EGFP
      expression was observed in muscle and brain tissues, in addition to the eyes.
      Also, when both TATA elements were mutated, transgenic animals had EGFP
      expression in all photoreceptors. Because no reporter activity was observed when
      either a 3.2-kb 5' extended region or the first intron of the mCAR gene was
      tested in Weri-Rb-1 cells, neither construct was examined in vivo. CONCLUSIONS:
      The data demonstrate that the regulatory functions of the known cis-elements in
      the mCAR promoter are highly dependent on location and nucleotide sequence
      conservation. The TATA elements and CBEs are crucial for driving both basal
      transcriptional activity and tissue specificity to cone photoreceptors and
      pinealocytes.

PMID- 15505033
TI  - Coordinated changes in classes of ribosomal protein gene expression is associated
      with light-induced retinal degeneration.
AB  - PURPOSE: To identify genes with altered expression levels in the degenerating
      retina in a light-induced retinal degeneration (LIRD) model. METHODS: Adult
      Sprague-Dawley rats were exposed to intense green light for 4 hours. After this
      treatment, the retinas were excised, RNA was extracted, and a cDNA library was
      prepared. The cDNA library was differentially cross-screened with probes
      representing 0-hour and 4-hour light-exposed rat retina. Transcripts with altered
      expression levels were sequenced and expression was confirmed by Northern blot
      analysis. Gene-specific primers were designed and used to examine the expression
      levels of other genes involved in protein synthesis. Promoter sequences of the
      ribosomal-binding protein (Rbp) genes were analyzed for transcription-binding
      sites. RESULTS: Of the 10,000 clones that were initially screened, 41 exhibited
      altered expression levels. Six of these corresponded to five known Rbp genes. Six
      additional Rbp genes were also examined. In total, 9 of 11 Rbp genes exhibited an
      increase in expression levels in response to a 4-hour light exposure. In
      contrast, the transcript levels of elongation factor 1alpha1 and 18S rRNA did not
      increase. The most abundant transcription factor-binding sites conserved in the
      promoter regions of all Rbp genes examined in this study include AP-1, Oct-1, V
      myb, USF, Pax-4, and the FOX family of transcription factors. CONCLUSIONS: The
      results indicate that light-induced retinal degeneration (LIRD) is associated
      with increased expression of specific Rbp genes. These Rbp genes may be involved
      in mediating visual cell loss in LIRD through a translational or an
      extraribosomal mechanism.

PMID- 15505034
TI  - The involvement of the rho-kinase pathway and its regulation in cytokine-induced
      collagen gel contraction by hyalocytes.
AB  - PURPOSE: To investigate the involvement of the Rho-kinase pathway in collagen gel
      contraction by hyalocytes. METHODS: An in vitro type I collagen gel contraction
      assay using cultured bovine hyalocytes was performed to evaluate the effect of
      PDGF-BB and TGF-beta2. The effect of both cytokines on the phosphorylation of
      myosin light chain (MLC) was analyzed by Western blot analysis. To confirm the
      involvement of the Rho-kinase pathway in the collagen gel contraction, the
      effects of Y27632, a specific Rho-kinase inhibitor were examined. The effect of
      hydroxyfasudil, another potent Rho-kinase inhibitor, was also evaluated. The
      expression of alpha-smooth muscle actin (alphaSMA) was analyzed by Western blot
      analysis to examine the myofibroblast-like transdifferentiation of the
      hyalocytes. RESULTS: Maximum collagen gel contraction was observed within 24
      hours after treatment with PDGF-BB and much stronger contraction with TGF-beta2,
      whose effect was time dependent, at least up to 5 days. Although transient and
      maximum MLC phosphorylation by PDGF-BB was observed at approximately 4 hours
      after stimulation (180.8%, P <0.01), TGF-beta2-elicited MLC phosphorylation
      occurred in a time-dependent manner at least up to 24 hours (220.0%, P <0.01) and
      was maintained up to 5 days. Y27632 demonstrated significant inhibition of
      collagen gel contraction induced by both cytokines. Hydroxyfasudil dose
      dependently (0.03-20.00 microM) prohibited the phosphorylation of MLC, and
      inhibited collagen gel contraction at a concentration corresponding to that which
      inhibited MLC phosphorylation. TGF-beta2, but not PDGF-BB, also caused
      myofibroblast-like transdifferentiation with alphaSMA overexpression, which was
      downregulated by hydroxyfasudil in part (P <0.01). CONCLUSIONS: The hyalocytes
      have a contractile property in the presence of PDGF-BB and TGF-beta2. Whereas
      PDGF-BB initiates collagen gel contraction by transient activation of the Rho
      kinase pathway, sustained activation of the Rho-kinase pathway and myofibroblast
      like transdifferentiation appears to be involved in the TGF-beta2-dependent
      contractile properties of hyalocytes.

PMID- 15505035
TI  - Identification of target genes regulated by FOXC1 using nickel agarose-based
      chromatin enrichment.
AB  - PURPOSE: To overcome the problem of antibody availability, often encountered
      during chromatin immunoprecipitation (ChIP) assays, nickel agarose-based
      chromatin enrichment (NACE) was developed. Based on the affinity of (His)-6
      tagged proteins for the nickel ion, this modified form of ChIP allows the
      isolation of chromatin in the absence of specific antibodies. METHODS:
      Nonpigmented ciliary epithelium cells were transfected with (His)-6-tagged FOXC1.
      FOXC1-enriched chromatin complexes were isolated by using the tight electrostatic
      interaction between histidine residues of the recombinant FOXC1 protein and
      nickel. One hundred fifty NACE-enriched clones were sequenced and subjected to in
      silico and biochemical analyses. RESULTS: Twenty-six clones were detected near
      known genes: Eight were near predicted but uncharacterized genes, eight were
      within areas where neither known nor predicted genes have yet been mapped, four
      were chimeric, and the rest were either repetitive (n=81) or poor-quality (n=23)
      sequences. Twenty of the 26 known genes were expressed in the eye. Five of the
      NACE-enriched clones (BMP2K, DACH, FVT-1, SIX-1, and PGE-2 receptor), as well as
      nine clones selected from the literature, were validated by PCR amplification in
      two independent lots of NACE-enriched chromatin. All five NACE-selected genes
      were detected in two independent assays, as well as four (BMP7, SMAD2, TGF-B1,
      and WNT6) of the nine genes selected from the literature, consistent with these
      genes' being regulated by FOXC1. CONCLUSIONS: NACE is a useful technique allowing
      specific chromatin enrichment in cases where antibodies are unavailable. Specific
      recovery of PTGER, DACH1, WNT6, and FVT-1 implicates FOXC1 in a variety of
      cellular events including modulation of intraocular pressure, cell cycle, ocular
      development, and oncogenesis.

PMID- 15505036
TI  - Incidence and progression of astigmatism in Singaporean children.
AB  - PURPOSE: This study investigated the incidence and progression, as well as
      factors associated with changes in astigmatism in school children. METHODS: This
      was a prospective cohort study. Children 7 to 9 years of age, of Chinese, Malay,
      and Asian Indian ethnicity, were examined annually over a 4-year period.
      Cycloplegic autorefraction was performed. A questionnaire was used to evaluate
      risk factors for incidence and progression of astigmatism. RESULTS: The
      cumulative 3-year incidence rate of astigmatism was 33.6% (cylinder power of 0.5
      D or worse) or 11.5% (cylinder power of 1.0 D or worse). Myopic children had a
      higher incidence rate of astigmatism than nonmyopes (P <0.001). The mean J0
      change per year was 0.012 D (95% CI: 0.007-0.018), whereas J45 did not show a
      significant change each year (mean, 0.001 D per year). Chinese children had
      greater worsening of J0 per year (P <0.001). Girls also had significantly greater
      progression of J0 than did boys (P <0.001). Similarly, myopia at baseline (P
      <0.001) and the hours of computer use (P=0.049) were associated with a greater
      progression rate of J0. J0 tended to improve in children with compound hyperopic
      astigmatism, worsen in children with compound myopic astigmatism, and remain
      stable in mixed astigmatics. CONCLUSIONS: Although there was minimal progression
      of astigmatism in school age children (0.44-0.53 D) over this period of follow
      up, incident cases of astigmatism (>1.0 D) were not uncommon. The progression
      rate of astigmatism was affected by the ethnicity, presence of myopia, axis, and
      subtype of astigmatism.

PMID- 15505037
TI  - Psychometric properties of the Veterans Affairs Low-Vision Visual Functioning
      Questionnaire.
AB  - PURPOSE: To describe psychometric properties of a self-report questionnaire, the
      Veterans Affairs (VA) Low-Vision Visual Functioning Questionnaire (LV VFQ-48),
      which was designed to measure the difficulty visually impaired persons have
      performing daily activities and to evaluate low-vision outcomes. METHODS: The VA
      LV VFQ-48 was administered by telephone interview to subjects with visual acuity
      ranging from near normal to total blindness at five sites in the VA and private
      sector. Rasch analysis with the Andrich rating scale model was applied to
      difficulty ratings from 367 subjects, to evaluate measurement properties of the
      instrument. RESULTS: High intercenter correlations for item measure estimates
      (intraclass correlation coefficient [ICC]=0.97) justified pooling the data from
      these sites. The person measure fit statistics (mean square residuals) confirm
      that the data fit the assumptions of the model. The item measure fit statistics
      indicate that responses to 19% of the items were confounded by factors other than
      visual ability. The separation reliabilities for pooled data (0.94 for persons
      and 0.98 for items) demonstrate that the estimated measures discriminate persons
      and items well along the visual ability dimension. ICCs for test-retest data
      (0.98 for items and 0.84 for persons) confirm temporal stability. Subjects used
      the rating categories in the same way at all five centers. Ratings of slight and
      moderate difficulty were used interchangeably, suggesting that the instrument
      could be modified to a 4-point scale including not difficult, slightly/moderately
      difficult, extremely difficult, and impossible. Fifty additional subjects were
      administered the questionnaire with a 4-point scale to confirm that the scale was
      used in the same way when there were four rather than five difficulty ratings.
      CONCLUSIONS: The VA LV VFQ-48 is valid and reliable and has the range and
      precision necessary to measure visual ability of low-vision patients with
      moderate to severe vision loss across diverse clinical settings.

PMID- 15505038
TI  - Familial aggregation of retinal vessel caliber in the beaver dam eye study.
AB  - PURPOSE: To describe familial correlations of retinal vessel measurements.
      METHODS: A standardized examination and interview was administered to a
      population-based cohort of adults aged 43-86 years. Blood pressure was measured,
      and family relationships, current smoking status, and photographs of the retina
      were obtained. Computer-assisted grading was done to determine central retinal
      arteriole (CRAE) and venule equivalents (CRVE), and the arteriole-to-venule ratio
      (AVR) was computed. Familial correlations were calculated using FCOR in the SAGE
      software package. Analysis was done on the right eye measures for 871 sibling,
      341 parent-child, 1362 cousin, 554 avuncular, and 887 spousal pairs. RESULTS:
      After adjustment for age, gender, mean arterial blood pressure, and current
      smoking status, the correlations (and 95% confidence interval) between siblings
      for the CRVE, CRAE, and AVR were 0.23 (0.16, 0.31), 0.20 (0.12, 0.28) and 0.13
      (0.05, 0.20), respectively. Parent-child correlations were very similar, and the
      avuncular correlations were about half as great. The cousin correlations were
      about half the avuncular correlations. Spousal correlations of 0.03, 0.04, and
      0.01 for CRVE, CRAE, and AVR, respectively, were not significantly different from
      0. CONCLUSIONS: Retinal vessel equivalents were more highly correlated between
      relatives than between unrelated individuals. The relative magnitudes of these
      correlations were likely the result of shared genes. Because the vessel
      measurements have been shown to be predictive of cardiovascular and other
      systemic diseases, understanding the determinants of these familial relationships
      could have important health benefits.

PMID- 15505039
TI  - Is glaucoma associated with motor vehicle collision involvement and driving
      avoidance?
AB  - PURPOSE: To evaluate the association between the diagnosis of glaucoma and motor
      vehicle collision (MVC) involvement and driving avoidance in drivers aged > or
      =50 years. METHODS: Two groups of patients, one with glaucoma and one without,
      were identified in three university-affiliated eye care practices. Demographic,
      clinical, and driving characteristics were obtained by chart abstractions and a
      patient survey. Information regarding MVC involvement was obtained from police
      records. RESULTS: Patients with glaucoma were less likely (relative risk [RR],
      0.67; 95% confidence interval [CI], 0.47-0.97) to be involved in collisions than
      patients without glaucoma. There was no difference between the at-fault crash
      rates of the patients with glaucoma and those without (RR, 1.22; 95% CI, 0.67
      2.22). Patients with glaucoma had significantly higher levels of avoidance for
      driving at night (odds ratio [OR], 2.06; 95% CI, 1.11-3.82), driving in fog (OR,
      3.80; 95% CI, 1.93-7.48), driving in the rain (OR, 2.99; 95% CI, 1.32-6.76),
      driving during rush hour (OR, 2.24; 95% CI, 1.16-4.34), driving on the highway
      (OR, 2.81; 95% CI, 1.19-6.64), and high density driving (OR, 2.88; 95% CI, 1.28
      6.46). These associations were adjusted for demographic and medical
      characteristics as well as visual acuity. CONCLUSIONS: Older persons with
      glaucoma drive at least as safely as, if not more safely than, older persons
      without glaucoma.

PMID- 15505040
TI  - Macular pigment and percentage of body fat.
AB  - PURPOSE: To investigate the relationship between percentage of body fat and
      macular pigment (MP) optical density. METHODS: One hundred healthy subjects of
      ages between 22 and 60 years volunteered to participate in this study. MP optical
      density was measured psychophysically, serum lutein and zeaxanthin were
      quantified by HPLC, and dietary intake of lutein and zeaxanthin was assessed
      using a validated food frequency questionnaire. Body fat was measured by dual
      energy x-ray absorptiometry (DEXA); body mass index (BMI) was also calculated for
      each subject. Clinical and personal details were recorded, with particular
      attention directed toward putative risk factors for AMD. RESULTS: There was a
      significant inverse relationship between the percentage of body fat and MP
      optical density in males (r=-0.392, P <0.01), and after correcting for age and
      dietary lutein and zeaxanthin, this inverse relationship remained significant (r=
      0.290, P <0.05). The relationship between MP optical density and percentage of
      body fat in females was inverse, but not significant (r=-0.197, P=0.149). A
      significant and inverse relationship between serum zeaxanthin and percentage of
      body fat was observed for females only (r=-0.354, P <0.01). Dietary intake of fat
      was inversely related to serum lutein and zeaxanthin, and significantly so for
      lutein (r=-0.256, P <0.05). However, dietary fat was unrelated to MP optical
      density (r=0.041, P=0.688). CONCLUSIONS: A relative lack of MP is associated with
      adiposity in men, and may underlie the association between body fat and risk for
      AMD progression in males. Further, the processes governing accumulation and/or
      stabilization of lutein and zeaxanthin in fat tissue appear to differ for males
      and females.

PMID- 15505041
TI  - Porcine corneal epithelial cells consist of high- and low-integrin beta1
      expressing populations.
AB  - PURPOSE: Immunohistochemically, all cells in the porcine corneal epithelium, from
      the superficial to the basal layer, express integrin beta1. Flow cytometric study
      has shown that they comprise integrin beta1 high-expressing (beta1 2+) and low
      expressing (beta1+) populations. This study was undertaken to determine their
      proliferation characteristics. METHODS: Epithelial cells from porcine corneas
      were sorted and labeled with anti-integrin beta1 antibody and a fluorescent-dye
      conjugated secondary antibody. The fluorescent intensity of labeled cells was
      analyzed and beta1 2+ and beta1+ cells were cultured in an adhesive-coated
      culture plate. RESULTS: Flow cytometry demonstrated that the epithelial cells
      comprised two distinct populations with a similar ratio throughout the cornea.
      Whereas beta1 2+ cells attached and grew to confluence in the plate, beta1+
      attached only transiently to the plate and exhibited minimal growth. CONCLUSIONS:
      The data indicate that the porcine cornea contains two distinct populations of
      epithelial cells, one exhibiting high and the other low integrin beta1
      expression. The observation that beta1 2+ cells had greater growth potential
      suggests that they may represent an enriched population of transit-amplifying
      cells.

PMID- 15505042
TI  - Pdlim2, a novel PDZ-LIM domain protein, interacts with alpha-actinins and filamin
      A.
AB  - PURPOSE: To characterize properties of Pdlim2, a novel PDZ and LIM domain
      containing protein. METHODS: cDNA encoding Pdlim2 was identified in a cDNA
      library of transcripts expressed in the tissues of the rat eye irido-corneal
      angle. The expression pattern of the Pdlim2 gene was studied by Northern blot
      analysis and in situ hybridization. Proteins interacting with Pdlim2 were
      identified by pull-down assay and mass spectrometry. Intracellular localization
      of Pdlim2 was investigated by confocal microscopy. RESULTS: Rat Pdlim2 protein
      belongs to the ALP subfamily of proteins containing the PDZ domain in the N
      terminal portion and the LIM domain in the C-terminal portion of the protein. The
      Pdlim2 gene was specifically expressed in the corneal epithelial cells, but not
      in the corneal stroma and endothelium nor in other ocular tissues. Pdlim2 was
      also expressed in the lung. In rat corneal and lung extracts, alpha-actinin-1,
      alpha-actinin-4, filamin A, and myosin heavy polypeptide 9 were co
      immunoprecipitated with Pdlim2. Myosin VI was co-immunoprecipitated with Pdlim2
      from corneal but not lung extracts. alpha-Actinins were the most abundant among
      immunoprecipitated proteins. Direct interaction of Pdlim2 with alpha-actinins and
      filamin was confirmed using pull-down assays and gel overlay assay with purified
      proteins. Pdlim2 and alpha-actinins were co-localized mainly to stress fibers
      after transfection into COS-7 cells. In transfected COS-7 cells, complexes of
      Pdlim2 and alpha-actinin-1 were preferentially located along the basal aspect.
      CONCLUSIONS: These results suggest that Pdlim2, like other ALP subfamily members,
      may act as an adapter that directs other proteins to the cytoskeleton.

PMID- 15505043
TI  - Inflammatory cytokines induce apoptosis of corneal endothelium through nitric
      oxide.
AB  - PURPOSE: Proinflammatory cytokines are integral components of the allogeneic
      response to a corneal transplant and contribute to the pathogenesis of graft
      failure that results from irreversible damage to donor corneal endothelium. As
      yet, the mechanism and effectors of tissue damage during graft rejection remain
      unidentified. In the current study, the synergistic apoptotic effect of sustained
      proinflammatory cytokine insult was investigated in excised cornea and in
      transformed and primary corneal endothelial cells. METHODS: Apoptosis was
      assessed by tissue- and flow cytometry-based TUNEL staining. Downstream signaling
      events of cytokine stimulation and subsequent activation status of endothelium
      were studied by RT-PCR and Western blot analysis. Cellular production of NO was
      examined by the Griess reaction. RESULTS: Prolonged exposure (48 hours) of
      corneal endothelium to IL-1, IFNgamma, and TNF (100 ng/mL each) resulted in
      induction of apoptosis. Synergy in induction of apoptosis was found after
      exposure to cytokine combinations. Cytokine-mediated cytotoxicity was correlated
      with high and sustained (up to 36 hours) endothelial activation (specifically
      through NF-kappaB, p38, and STAT-1), upregulation of inducible nitric oxide
      synthase (iNOS), and elevated de novo production of NO. Pharmacologic inhibition
      of iNOS elicited complete cytoprotection from inflammatory cytokine insult.
      CONCLUSIONS: The specific release of proinflammatory cytokines from alloreactive
      infiltrating cells, in combination with the inflamed environment of a corneal
      allograft, results in apoptosis in the corneal endothelium. This effect is
      mediated by the de novo generation of NO and sustained activation of NF-kappaB,
      p38, and STAT-1. Inflammatory cytokine-induced apoptosis presents a new target
      for the development of interventions to prevent or attenuate endothelial injury
      in graft rejection.

PMID- 15505044
TI  - Effect of overexpression of constitutively active PKCalpha on rat lacrimal gland
      protein secretion.
AB  - PURPOSE: The lacrimal gland secretes water, electrolytes, and protein into the
      tear film. Decreased secretion from the lacrimal gland can lead to dry eye
      syndromes with deleterious effects on vision. Protein kinase C (PKC)-alpha plays
      a major role in cholinergic- and alpha1-adrenergic-induced protein secretion from
      the lacrimal gland. This study was undertaken to determine whether activation of
      PKCalpha alone would induce lacrimal gland protein secretion by examining the
      effects of overexpression of constitutively active PKCalpha. METHODS: Rat
      lacrimal gland acini were transduced with an adenovirus containing a gene for
      constitutively active PKCalpha. Protein secretion was measured in response to
      cholinergic and alpha1-adrenergic agonist stimulation. RESULTS: More than 84% of
      acinar cells were transduced, and PKCalpha expression was increased 176-fold.
      Western blot analysis using an antibody to phosphorylated (activated) PKCalpha
      indicated that the overexpressed PKCalpha was active, and basal secretion was
      increased. Cholinergic agonist-stimulated protein secretion was not stimulated
      above basal secretion, whereas alpha1-adrenergic-agonist-stimulated protein
      secretion was increased in transduced acini. CONCLUSIONS: Basal lacrimal gland
      protein secretion can be stimulated by bypassing the release of neurotransmitters
      and activating PKCalpha, possibly leading to the development of new treatments
      for dry eye syndromes.

PMID- 15505045
TI  - Hyperexpression of low-density lipoprotein receptors and hydroxy-methylglutaryl
      coenzyme A-reductase in human pinguecula and primary pterygium.
AB  - PURPOSE: There is now increasing evidence that pterygium and pinguecula are
      tumorlike tissues and that cell growth and DNA replication are closely linked to
      cholesterol metabolism. In this study, the expression of two main genes
      correlated to cholesterol metabolism--namely, the low-density lipoprotein
      receptor (LDL-R) gene and the hydroxy-methylglutaryl-coenzyme A-reductase (HMG
      CoA-R) gene--were investigated in primary pterygium, pinguecula, and normal
      conjunctiva. METHODS: Pterygium, pinguecula, and normal conjunctiva samples were
      obtained from 30 eyes (50% men) at the time of surgery. Total RNA extracted from
      the specimens was subjected to semiquantitative reverse transcription-polymerase
      chain reaction (RT-PCR). Equal amounts of total RNA were reverse transcribed into
      cDNA. The cDNA was subsequently amplified by the PCR in the presence of specific
      primers for low-density lipoprotein receptor (LDL-R) and for hydroxy
      methylglutaryl coenzyme A reductase (HMG-CoA-R). RESULTS: Semiquantitative RT-PCR
      analysis revealed that the mRNA levels of LDL-R and HMG-CoA-R were increased in
      pterygia, compared with levels in both pingueculae and normal conjunctivae.
      Differences were statistically significant (P <0.05), including pingueculae
      versus normal conjunctivae. CONCLUSIONS: This study indicates that pterygium and
      pinguecula have an altered metabolism of cholesterol-namely increased LDL-R and
      HMG-CoA-R mRNAs-as is characteristic of tumorlike tissues, and that the high
      expression of LDL receptors renders them amenable to be treated by photodynamic
      therapy with intravenously injected verteporfin.

PMID- 15505046
TI  - Ocular higher-order aberrations and contrast sensitivity after conventional laser
      in situ keratomileusis.
AB  - PURPOSE: To investigate prospectively the relation between induced changes in
      higher-order aberrations of the eye and changes in contrast sensitivity by
      conventional laser in situ keratomileusis (LASIK) for myopia. METHODS: In 200
      eyes of 110 consecutive patients (mean age, 32.7 +/- 8.4 years) undergoing LASIK,
      ocular aberrations and contrast sensitivity function were determined before and 1
      month after surgery. The amount of myopic correction was 5.2 +/- 2.8 D (range,
      1.0-13.0). Ocular higher-order aberrations were measured for a 4-mm pupil using
      the Hartmann-Shack wavefront analyzer (KR-9000PW; Topcon, Tokyo, Japan). The root
      mean square (RMS) of the third- and fourth-order Zernike coefficients was used to
      represent coma- and spherical-like aberrations, respectively. Total higher-order
      aberrations were calculated as the RMS of the third- and fourth-order
      coefficients. Contrast sensitivity and low-contrast visual acuity were measured.
      From the contrast sensitivity data, the area under the log contrast sensitivity
      function (AULCSF) was calculated. RESULTS: LASIK significantly improved logMAR
      best corrected visual acuity (Wilcoxon signed-rank test, P <0.001), but
      significantly reduced AULCSF (P <0.001) and low-contrast visual acuity (P=0.007).
      Total higher-order (P <0.001), coma-like (P <0.001), and spherical-like (P
      <0.001) aberrations were significantly increased after LASIK. The greater the
      amount of achieved myopia correction was, the more the changes in contrast
      sensitivity function and ocular higher-order aberrations were. The induced
      changes in AULCSF by LASIK showed significant correlations with changes in total
      higher-order (Pearson r=-0.221, P=0.003), coma-like (r=-0.205, P=0.006), and
      spherical-like (r=-0.171, P=0.022) aberrations. The changes in logMAR low
      contrast visual acuity by surgery significantly correlated with changes in total
      higher-order (r=0.222, P=0.003), coma-like (r=0.201, P=0.007), and spherical-like
      (r=0.207, P=0.005) aberrations. CONCLUSIONS: Conventional LASIK significantly
      increases ocular higher-order aberrations, which compromise the postoperative
      contrast sensitivity function.

PMID- 15505047
TI  - Corneal reinnervation after LASIK: prospective 3-year longitudinal study.
AB  - PURPOSE: To measure the return of innervation to the cornea during 3 years after
      LASIK. METHODS: Seventeen corneas of 11 patients who had undergone LASIK to
      correct myopia from -2.0 D to -11.0 D were examined by confocal microscopy before
      surgery, and at 1, 3, 6, 12, 24, and 36 months after surgery. In all available
      scans, the number of nerve fiber bundles and their density (visible length of
      nerve per frame area), orientation (mean angle), and depth in the cornea were
      measured. RESULTS: The number and density of subbasal nerves decreased >90% in
      the first month after LASIK. By 6 months these nerves began to recover, and by 2
      years they reached densities not significantly different from those before LASIK.
      Between 2 and 3 years they decreased again, so that at 3 years the numbers
      remained <60% of the pre-LASIK numbers (P <0.001). In the stromal flap most nerve
      fiber bundles were also lost after LASIK, and these began recovering by the third
      month, but by the third year they did not reach their original numbers (P
      <0.001). In the stromal bed (posterior to the LASIK flap interface), there were
      no significant changes in nerve number or density. As the subbasal nerves
      returned, their mean orientation did not change from the predominantly vertical
      orientation before LASIK. Nerve orientation in the stromal flap and the stromal
      bed also did not change. CONCLUSIONS: Both subbasal and stromal corneal nerves in
      LASIK flaps recover slowly and do not return to preoperative densities by 3 years
      after LASIK. The numbers of subbasal nerves appear to decrease between 2 and 3
      years after LASIK. The orientation of the regenerated subbasal nerves remains
      predominantly vertical.

PMID- 15505049
TI  - Corneal thickness determination and correlates in Singaporean schoolchildren.
AB  - PURPOSE: To determine the central cornea thickness (CCT) in Singaporean children
      and to examine the possible relationship between intraocular pressure (IOP) and
      other biometric factors and CCT. METHODS: This was a cross-sectional study. The
      subjects (N=652) were obtained from the Singapore Cohort Study of the Risk
      Factors for Myopia (SCORM). The subjects' ages ranged from 9 to 11 years. There
      were 485 Chinese, 92 Malayan, and 75 Asian Indian children. Measurement
      procedures included air-puff tonometry, noncontact slit lamp optical pachymetry,
      cycloplegic autorefraction, and autokeratometry. RESULTS: The mean CCT was 543.6
      +/- 32.0 microm. Chinese children had thicker corneas than Malayan or Indian
      children (P=0.002). The boys had thicker corneas than girls (P=0.011), but the
      mean difference was only 6.4 microm. There was high correlation of CCT (r=0.98)
      and IOP (r=0.88) between right and left eyes. IOP was correlated with CCT
      (r=0.45, P <0.001). In a multiple linear regression model, each millimeter of
      mercury of IOP was associated with a CCT difference of 5.90 microm (95%
      confidence interval [CI], 4.98-6.82). The radius of corneal curvature correlated
      with CCT (r=0.19, P <0.001). The following parameters were not significantly (P
      >0.05) associated with CCT: age, family income, father's education, axial length,
      and spherical equivalent. CONCLUSIONS: The mean CCT in Singaporean children aged
      9 to 11 years was 543.6 microm and showed ethnic and gender variation. CCT
      affected measured IOP and correlated weakly with corneal curvature. Compared with
      data in adults, a change in CCT was associated with a greater difference in
      measured IOP.

PMID- 15505048
TI  - Expression of phospholipases A2 and C in human corneal epithelial cells.
AB  - PURPOSE: To achieve a better understanding of the involvement of phospholipases
      in the inflammation and wound-healing processes in human corneal epithelial cells
      (HCECs), expression of phospholipase A2s (PLA2s) and phospholipase Cs (PLCs) was
      examined in the human corneal epithelium. METHODS: Specific primers were designed
      for RT-PCR amplification of the known secreted (s)PLA2, cytosolic (c)PLA2, and
      PLC mRNAs. Corresponding PCR products were cloned and the DNA sequenced.
      Immunofluorescence of flatmounted corneal sections and Western blot analyses were
      used to detect the PLA2s and PLCs expressed by HCECs. RESULTS: The mRNAs for the
      following phospholipases were detected by RT-PCR in the HCECs: sPLA2GIII, -GX,
      and -GXIIA; cPLA2alpha and -gamma; PLCbeta1, -beta2, -beta3, -beta4, -gamma1, 
      gamma2, -delta1, -delta3, -delta4, and -epsilon. Immunofluorescence analyses
      conducted on corneal epithelium cryosections and Western blot on freshly isolated
      HCECs demonstrated the presence of sPLA2GIII, -GX, and -GXIIA; cPLA2alpha and 
      gamma; and PLCbeta2, -beta3, -gamma1, -gamma2, and -delta3. CONCLUSIONS: Many
      phospholipase isoforms are expressed by HCECs and may play a major role in signal
      transduction (PLCs) as well as in the release of precursors of potent mediators
      of inflammation, such as leukotrienes and prostaglandins (PLA2s). Moreover, the
      sPLA2s expressed by the corneal epithelium could be involved in the normal
      antibacterial activity in the tears and in wound healing.

PMID- 15505050
TI  - Uncoupling keratocyte loss of corneal crystallin from markers of fibrotic repair.
AB  - PURPOSE: Corneal crystallins are lost from resident cells of the corneal stroma
      during wound repair, and this is associated with a loss of cell transparency. The
      goal of this study was to identify factors inducing loss of the corneal
      crystallin transketolase (TKT). METHODS: A cell culture model of freshly isolated
      rabbit corneal keratocytes was used. Fibrotic markers included cell
      proliferation, adoption of a "fibroblastic" spindle-shaped morphology associated
      with cytoskeletal rearrangement, loss of TKT, and expression of alpha-smooth
      muscle actin (alpha-sm actin), a marker for the myofibroblast. RESULTS: When
      freshly isolated keratocytes were cultured in the continuous presence of 10% calf
      serum, the high level of intracellular TKT protein was reduced dramatically
      within 24 to 48 hours. In contrast, TKT protein was retained in cells maintained
      in the absence of serum. When cells were prevented from proliferating by exposure
      to serum for <24 hours or by continuously exposing to serum at a contact
      inhibiting plating density, TKT loss was inhibited. TKT loss was induced by
      treatment of serum-free cultures with the serum cytokines platelet-derived growth
      factor or basic fibroblast growth factor, both of which also stimulated
      keratocyte proliferation, although not other changes associated with fibrosis.
      However, TKT loss was not induced by treatment of serum-free cultures with a
      third serum cytokine, transforming growth factor- (TGF)-beta, even though TGF
      beta stimulated cell proliferation at low doses and induced the fibroblastic
      spindle-shape and express alpha-sm actin at high doses. CONCLUSIONS: TKT loss in
      corneal keratocytes can be induced by PDGF or bFGF and this loss can be uncoupled
      from other fibrotic markers. Targeting these cytokines or the signaling pathways
      that they activate could enable retention of corneal crystallin in stromal cells
      during repair, a more regenerative outcome. The result would be enhanced clarity
      of the cornea.

PMID- 15505051
TI  - Recovery of contour integration in relation to LogMAR visual acuity during
      treatment of amblyopia in children.
AB  - PURPOSE: In several studies, researchers have found that integration of
      orientation information along contours defined by Gabor patches is abnormal in
      patients with strabismus and in untreated patients with anisometropic amblyopia.
      In this study, the rate and degree of recovery of contour-integration deficits
      were compared with the recovery of logMAR (logarithm of the minimum angle of
      resolution) visual acuity deficits in patients newly diagnosed with amblyopia
      secondary to anisometropia, strabismus, or both. METHOD: Contour-detection
      thresholds and optotype acuity were measured in 17 newly diagnosed anisometropic
      amblyopes, in 6 patients with strabismic amblyopia, and in 4 patients with
      combined anisometropic and strabismic amblyopia. Contour-detection thresholds
      were measured with a card-based procedure. Treatment comprised full refractive
      correction and full-time total occlusion therapy, when necessary. Visual function
      was measured at monthly visits during the course of treatment, with an average
      follow-up period of 16 weeks (12-24 weeks) for the entire group. Complete data
      were obtained from 23 patients through 8 weeks of follow-up. RESULTS: Significant
      interocular differences in contour-detection thresholds were present in 16 of the
      27 patients at the first visit after initial refractive correction. Interocular
      differences in contour-detection thresholds declined to normal levels in most of
      the patients within 8 weeks of the initiation of treatment. Interocular acuity
      differences remained significant in many of the patients (19/23) at 8 weeks of
      follow-up and continued to decline, but did not fully normalize, over the
      remainder of the follow-up period. CONCLUSIONS: Refractive correction alone or in
      combination with occlusion therapy produces a normalization of contour
      integration thresholds in amblyopia that is more rapid and complete than that
      achieved for visual acuity.

PMID- 15505052
TI  - Gene and protein expression changes in human trabecular meshwork cells treated
      with transforming growth factor-beta.
AB  - PURPOSE: To determine the genomic and proteomic expression changes in human
      trabecular meshwork cells when they are treated with transforming growth factor
      (TGF)-beta. METHODS: Human trabecular meshwork cells from five donors were
      cultured for 3 days with 1 ng/mL of either TGF-beta1 or -beta2. Changes in gene
      expression determined with gene microarrays and alterations in protein expression
      detected by two-dimensional gel electrophoresis and matrix-assisted laser
      desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) were
      studied in these cells after the incubation. RESULTS: With both TGF-betas, there
      was a substantial upregulation of genes that were related to secreted proteins or
      extracellular matrix. This result was consistent with pathologic changes observed
      in disease and with experiments on perfused trabecular meshwork. Several of the
      gene changes suggest that other signaling pathways, such as ErbB and Wnt, were
      altered. Changes in enzyme expression in the prostaglandin pathway indicated that
      the prostaglandins may have a different cellular profile in the presence of
      glaucoma. Two genes, osteoblast-specific factor 2 and corneal-derived transcript
      6, which are highly expressed in the cells under normal conditions, were
      substantially upregulated with the TGF-betas. Proteomic analysis indicated that
      there was increased proteolysis of vimentin with both treatments. Tropomyosin
      1alpha was increased in both gene and protein expression, suggesting alterations
      of the cytoskeleton by the disease. The TGF-beta1 treatment caused more robust
      changes than those induced by TGF-beta2. Three genes-aldose reductase,
      thioredoxin reductase 1, and glucose-6-phosphate 1-dehydrogenase-were identified
      that were downregulated in expression. These genes had decreases in protein
      expression with TGF-beta1 treatment but had little change in either gene or
      protein expression with TGF-beta2. CONCLUSIONS: Human trabecular meshwork cells
      can be subjected to increased levels of TGF-beta for several years as a result of
      glaucoma. The results indicate that changes in extracellular matrix as well as
      alterations in cytoskeletal proteins occur in these cells as a result of
      increased TGF-beta. These results are consistent with changes observed in the
      trabecular meshwork in glaucoma and suggest that at least some of the histologic
      alterations observed in the meshwork in glaucoma may be the result of increased
      TGF-betas.

PMID- 15505053
TI  - Test-retest variability of multifocal visual evoked potential and SITA standard
      perimetry in glaucoma.
AB  - PURPOSE: To investigate the test-retest variability of multifocal visual evoked
      potential (mfVEP) and threshold perimetry in glaucoma, and to examine the
      relationship between the two techniques. METHODS: Data were recorded using the
      AccuMap mfVEP and SITA standard program of the Humphrey Field Analyzer. Data were
      obtained twice within a 4-week period from both eyes of 74 patients with varying
      amounts of glaucomatous visual field loss. The number of defective test locations
      (those falling beyond a given probability value of being normal) were calculated
      for mfVEP and SITA, using databases incorporated within the instruments software.
      Reliability measures and test times were recorded along with patient test
      preference. RESULTS: Both tests showed a large degree of test-retest variability
      in the number of defective test locations (95% limits of agreement for mfVEP and
      SITA being 13.39 and 9.88, respectively). A "fair to moderate" degree of spatial
      agreement was found between mfVEP and SITA. The number of mfVEP defective
      locations was dependent on the signal amplitude. No relationship was found
      between test-retest variability and the reliability indices for either test. The
      mean time taken to perform mfVEP and SITA standard was 33 and 20 minutes,
      respectively, and 73 of the 74 patients preferred the mfVEP test. CONCLUSIONS:
      Test-retest variability was found to be slightly greater for mfVEP. The
      processing of mfVEP signals needs to be changed to remove the relationship
      between the number of defective locations and signal amplitude. The majority of
      patients preferred mfVEP to conventional perimetry although mfVEP takes longer to
      perform.

PMID- 15505054
TI  - Effects of topically instilled bunazosin, an alpha1-adrenoceptor antagonist, on
      constrictions induced by phenylephrine and ET-1 in rabbit retinal arteries.
AB  - PURPOSE: To examine the inhibitory effects of topically instilled bunazosin
      hydrochloride (bunazosin), a selective alpha1-adrenoceptor antagonist, on the
      retinal artery constrictions induced by intravitreous phenylephrine hydrochloride
      (phenylephrine) and endothelin (ET)-1 in rabbits. METHODS: Phenylephrine or ET-1
      (20 microL) was injected into the central part of the vitreous in both eyes in
      pigmented rabbits. Color fundus photographs were taken at 5 minutes before and 60
      minutes after the injection. The average diameter of the major retinal arteries
      at the rim of the optic nerve head (ONH) was normalized with respect to ONH
      diameter. Bunazosin was instilled into one eye (chosen randomly) and vehicle into
      the fellow eye at 60 minutes before the intravitreous injection. To examine any
      interaction between the alpha1-adrenoceptor and ET receptor, phenylephrine and ET
      1 were co-injected at individually ineffective doses. In addition, ET-1-induced
      vasoconstriction was examined after unilateral superior cervical ganglionectomy.
      The binding affinities of bunazosin for ETA and ETB receptors were also
      evaluated. The series of experiments was performed as masked tests. RESULTS:
      Retinal arteries were dose-dependently constricted by both intravitreous
      phenylephrine and intravitreous ET-1. Topically instilled bunazosin at 0.01%
      partly inhibited both of these vasoconstrictions on the ipsilateral side, but not
      on the contralateral side. Bunazosin did not bind to ET receptors. Co-injection
      of phenylephrine and ET-1 at individually ineffective doses constricted retinal
      arteries significantly. An adrenergic supersensitivity in retinal arteries was
      observed after superior cervical ganglionectomy only on the ganglionectomized
      eye. The ET-1-induced vasoconstriction was significantly weaker in cervical
      ganglionectomized eyes than in sham-surgery eyes. CONCLUSIONS: The present
      findings suggest that topically instilled bunazosin reaches the posterior retina
      by local penetration at concentrations sufficient to attenuate the phenylephrine-
      or ET-1-induced constriction of retinal arteries in normal rabbit eyes, and that
      the inhibitory effect of bunazosin on the ET-1-induced vasoconstriction in this
      tissue may be partly attributable to an interaction between the alpha1
      adrenoceptor and ET receptor.

PMID- 15505055
TI  - Caspase-independent component of retinal ganglion cell death, in vitro.
AB  - PURPOSE: Although in vitro and in vivo models demonstrate caspase activation in
      retinal ganglion cells (RGCs) undergoing apoptosis, the caspase-independent
      component of RGC death is unclear. Identification of the precise mechanisms of
      cell death in these distinct neurons is essential for the development of
      effective neuroprotective strategies in glaucoma. Because TNF-alpha and hypoxia
      have been implicated in RGC death during glaucomatous optic nerve degeneration,
      this study was conducted to determine whether RGCs survive exposure to TNF-alpha
      or hypoxia in the presence of caspase inhibitor treatment, and whether
      mitochondrial dysfunction is involved in RGC death induced by these glaucomatous
      stimuli. METHODS: Primary cultures of rat RGCs were exposed to TNF-alpha or
      hypoxia for up to 48 hours. The temporal relationship of RGC death with the loss
      of mitochondrial membrane potential and the release of cell death mediators,
      including cytochrome c and apoptosis-inducing factor (AIF), was studied in the
      absence and presence of specific inhibitors of caspases. In addition, treatment
      with a free-radical scavenger, 4-hydroxytetramethylpiperidine-1-oxyl (tempol; 5
      mM), was used in some experiments. Cell viability was assessed using calcein
      assay, and annexin V binding combined with propidium iodide staining was used for
      the distinction of apoptotic and necrotic cells. Caspase-3-like protease activity
      was measured using a fluorometric assay, and for the in situ detection of caspase
      activity, immunocytochemistry was performed with a cleavage-site-specific
      antibody. The time course of alterations in the mitochondrial membrane potential
      and the release of cell death mediators in individual cells undergoing cell death
      were assessed with a fluorescent tracer and subsequent immunocytochemistry. In
      addition, a fluorescent dye, dihydroethidium was used to assess the generation of
      reactive oxygen species (ROS). RESULTS: Findings of this study revealed that the
      loss of mitochondrial membrane potential and the release of cell death mediators
      accompanied RGC death induced by TNF-alpha or hypoxia. Although caspase inhibitor
      treatment temporarily decreased the rate of apoptosis, caspase inhibition was not
      adequate to block RGC death if the mitochondrial membrane potential was lost and
      mitochondrial mediators were released. Despite the inhibited caspase activity,
      survival rate was less than 70% after a 48-hour incubation with death stimuli,
      and both apoptotic and necrotic cells were detectable in these cultures. When
      combined with caspase inhibition, tempol reduced the production of ROS and
      provided an additional 20% increase in RGC survival. CONCLUSIONS: Based on these
      novel findings, RGC death induced by TNF-alpha or hypoxia involves a caspase
      independent component, and reducing the free-radical generation provides
      additional protection of RGCs temporarily saved by caspase inhibition. Therefore,
      neuroprotective strategies in glaucoma should include tools to improve the
      ability of these neurons to survive the cytotoxic consequences of mitochondrial
      dysfunction.

PMID- 15505056
TI  - Myelin/oligodendrocyte glycoprotein-specific T-cells induce severe optic neuritis
      in the C57BL/6 mouse.
AB  - PURPOSE: The optic nerve is a common site of tissue damage in multiple sclerosis
      (MS) and experimental autoimmune encephalomyelitis (EAE). To determine the
      relationship between optic neuritis (ON) and EAE, we examined the incidence of ON
      in C57BL/6 (B6) mice immunized with a myelin oligodendrocyte/glycoprotein (MOG)
      derived peptide or injected with MOG-specific T cells, which are known to induce
      EAE. METHODS: Mice were immunized with MOG35-55 or MOG40-54 peptides emulsified
      in complete Freund's adjuvant (CFA). Pertussis toxin (PTX) was injected
      intraperitoneally 1 day before and after immunization. For disease induction by
      adoptive transfer of primed cells, donor C57BL/6 mice were received with T-cell
      blasts (1-6 x 10(6)/mouse). Both EAE and ON were observed by either clinical
      signs or histology. RESULTS: ON developed in a high proportion of B6 mice treated
      with either protocol. The most severe inflammation was observed in the adoptively
      transferred mice. The induced ON was most frequently bilateral. In either
      actively or adoptively transferred diseases, both association and dissociation of
      EAE and ON was observed. CONCLUSIONS: Different MOG-specific T-cell subsets might
      be involved in the pathogenesis of EAE and ON. A better understanding of the
      pathogenesis of ON after induction by MOG may have important diagnostic and
      therapeutic implications.

PMID- 15505058
TI  - Matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in
      the human lens: implications for cortical cataract formation.
AB  - PURPOSE: To characterize the expression of matrix metalloproteinases (MMPs) and
      tissue inhibitors of matrix metalloproteinases (TIMPs) in human cortical cataract
      and to determine whether there is a correlation with the localization of cortical
      cataract. To evaluate the expression and activity of MMPs and TIMPs after
      cytokine and UV-B exposure in a human lens epithelial cell line. METHODS: Twenty
      eight human donor eyes with cortical cataract and 21 normal human donor eyes were
      photographed. Thirteen cortical cataract and six normal lenses were
      immunohistochemically analyzed for MMP-1, -2, -3, and -9 and TIMP-1, -2, and -3.
      Twelve fresh cortical cataract and 12 normal lenses were divided into quadrants
      to quantify, by ELISA, the expression of MMP-1, -2, -3, and -9 and TIMP-1. Three
      fresh cortical cataract and three control lenses were assessed for MMP-1, -2, and
      -9 activity by SDS-PAGE zymography. Human lens epithelial cells (HLE-SRA-01/04)
      were exposed to proinflammatory cytokines and UV-B radiation to determine the
      protein expression profiles of MMP-1, -2, -3, and -9 and TIMP-1 and -2. RESULTS:
      Immunohistochemical analysis revealed specific localization of MMP-1 within lens
      epithelium and cortical lens fibers of cortical cataract. Normal lenses had
      equally low MMP-1, -2, -3, and -9 and TIMP-1, -2, and -3 immunoreactivity,
      expression, and activity in all lens quadrants. IL-1 and TNF-alpha upregulated
      the expression of MMP-2, -3, and -9, and UV-B upregulated the expression of MMP-1
      in the SRA-01/04 HLE cell line. CONCLUSIONS: This is the first study to localize
      the expression of MMP-1 in cataracts with clinically observed opacification in
      vivo and to examine the expression induced by UV-B, in vitro.

PMID- 15505057
TI  - Hypoxia increases corneal cell expression of CFTR leading to increased
      Pseudomonas aeruginosa binding, internalization, and initiation of inflammation.
AB  - PURPOSE: To investigate the effect of hypoxia-induced molecular responses of
      corneal epithelial cells on the surface of rabbit and human corneas and corneal
      cells in culture on interactions with Pseudomonas aeruginosa that may underlie
      increased susceptibility to keratitis. METHODS: Organ cultures of rabbit and
      human corneal tissue, primary rabbit and human corneal cells, and transformed
      human corneal cells from a patient with cystic fibrosis and the same cell line
      corrected for expression of wild-type cystic fibrosis transmembrane conductance
      regulator (CFTR), the cellular receptor for P. aeruginosa, were exposed to
      hypoxic conditions for 24 to 72 hours. Changes in binding and internalization of
      P. aeruginosa were measured using cellular association and gentamicin-exclusion
      assays, and expression of CFTR and activation of NF-kappaB in response to hypoxia
      were determined by confocal laser microscopy and quantitative measurements of NF
      kappaB activation. RESULTS: Hypoxia induced in a time- and oxygen-concentration
      dependent manner increased association and internalization of clinical isolates
      of P. aeruginosa in all cells tested. Hypoxia increased CFTR expression and NF
      kappaB nuclear translocation in rabbit and human cells with wild-type CFTR.
      Corneal cells lacking CFTR had reduced NF-kappaB activation in response to
      hypoxia. Hypoxia did not affect the increase in corneal cell CFTR levels or NF
      kappaB activation after P. aeruginosa infection. CONCLUSIONS: Hypoxic conditions
      on the cornea exacerbate the binding and internalization of P. aeruginosa due to
      increased levels of CFTR expression and also induce basal NF-kappaB activation.
      Both of these responses probably exacerbate the effects of P. aeruginosa
      infection by allowing lower infectious doses of bacteria to induce disease and
      promote destructive inflammatory responses.

PMID- 15505059
TI  - Chick delta1-crystallin enhancer influences mouse alphaA-crystallin promoter
      activity in transgenic mice.
AB  - PURPOSE: Both the -366/+43 and the -282/+43 mouse alphaA-crystallin (or alphaA)
      promoters have been effective at driving transgene expression in lens fiber
      cells, but not in lens epithelium. Because the chick delta1-crystallin gene is
      expressed in lens epithelial cells, an enhancer was borrowed from this gene and
      linked to the alphaA promoter. This heterogenic enhancer/promoter construct was
      tested in transgenic mice to see whether it was active in both lens epithelium
      and fiber cells while retaining lens specificity. METHODS: The third intron of
      the chick delta1-crystallin gene, which contains a lens enhancer element, was
      added to the 5' end of the mouse alphaA promoter. We refer to this chimeric
      regulatory element as the deltaenalphaA promoter. To test its activity, we
      inserted coding sequences for five different genes. Transgenic mice were
      generated by pronuclear microinjection. Transgene expression patterns were
      analyzed by either X-gal staining, in situ hybridization or immunohistochemical
      staining. RESULTS: When deltaenalphaA-lacZ transgenic embryos were stained with X
      gal at embryonic day (E)11.5, beta-galactosidase activity was detected only in
      the eye. Histologic sections of the stained embryos revealed that lacZ was
      expressed exclusively in the lens, in both epithelial and fiber cells. Transgenic
      mice were also generated using either the original alphaA- or the new
      deltaenalphaA promoter linked to an insulin cDNA. In situ hybridizations
      confirmed that the short alphaA promoter targeted prenatal insulin expression
      specifically to the lens fiber cells, whereas the deltaenalphaA promoter was
      active in both lens epithelial and fiber cells. Developmental studies of the
      deltaenalphaA-insulin mice showed that the deltaenalphaA promoter became active
      at the lens pit stage and remained active in all lens cells, even at postnatal
      ages. The deltaenalphaA promoter also successfully directed expression of SV40 T
      antigen (TAg), human E2F2, and dominant negative Sprouty2 (dn-Spry2) genes to
      lens epithelial and fiber cells. The lens specificity of the deltaenalphaA
      promoter was maintained in minigenes with different types of introns and
      polyadenylation signals. CONCLUSIONS: A new lens-specific regulatory element was
      generated-the deltaenalphaA promoter, which can drive high levels of transgene
      expression in both lens epithelium and fiber cells throughout development. This
      modified promoter can be used for future transgenic studies of signal
      transduction and cell cycle regulation in lens epithelial cells.

PMID- 15505060
TI  - Lenticular levels of amino acids and free UV filters differ significantly between
      normals and cataract patients.
AB  - PURPOSE: To determine the levels of free UV filters and selected amino acids in
      cataract lenses compared with normal lenses. METHODS: Indian cataract lenses
      (n=39) and normal lenses (n=6) were examined by HPLC to quantify levels of UV
      filter compounds, the UV filter precursor amino acid tryptophan (Trp), as well as
      tyrosine (Tyr) and uric acid. RESULTS: The levels of the two major primate UV
      filters, 3-hydroxykynurenine glucoside (3OHKG) and 4-(2-amino-3-hydroxyphenyl)-4
      oxobutanoic acid glucoside (AHBG), in cataract lenses were markedly decreased
      compared with levels in normal lenses. By contrast, the levels of Trp were
      greatly increased. Mean Trp concentrations were an order of magnitude higher than
      in normal lenses, with 86% of dark-colored cataract lens nuclei having Trp
      concentrations greater than the mean level in the normal lenses. The
      concentrations of Tyr were also higher in cataract lenses. The levels of Kyn,
      however, were unchanged, and the uric acid levels were substantially lower.
      CONCLUSIONS: The levels of the free UV filter compounds 3OHKG and AHBG, and also
      of Trp, Tyr, and uric acid were different in cataract lenses compared to normal
      lenses. These data suggest that the metabolism of a large proportion of patients
      with cataract may be substantially different than in persons with normal lenses.
      Although the mechanism of such metabolic defects are unknown, the authors
      speculate that an amino acid transporter system may be upregulated in patients
      with cataract. Because kynurenine levels in cataract were not significantly
      different from those of normal lenses, there may be a defect in the lenticular UV
      filter pathway at one, or both, of the steps that convert kynurenine to 3OHKG.

PMID- 15505061
TI  - Compartmental analysis of taurine transport to the outer retina in the bovine
      eye.
AB  - PURPOSE: To assess the relative resistance presented individually by Bruch's
      membrane-choroid (BC) and the retinal pigment epithelium (RPE) to movement of
      taurine between the choroidal circulation and the outer retina. To quantify the
      effect of light-evoked changes in subretinal potassium concentration on the
      transepithelial transport of taurine across bovine RPE. METHODS: Transport
      studies were performed in Ussing chambers with intact and RPE-denuded specimens
      of BC. RPE viability was monitored by recording transepithelial potential (TEP)
      and transepithelial resistance (TER). Taurine transport with substrate
      concentrations in the micro- and millimolar range, reflecting physiological
      taurine concentrations in plasma, retina, and subretinal space was quantified by
      high-performance liquid chromatography (HPLC) and radiotracer techniques. Taurine
      transport was also assessed after apical potassium concentration was lowered from
      6.0 to 2.2 mM to mimic the effects of light. RESULTS: Transport of taurine across
      RPE-BC at a 10-mM substrate concentration increased from 32.92 before to 111.72
      nanomoles/4 mm per hour after removal of the RPE. Similarly, at 50 microM
      taurine, transport rates increased from 0.158 to 0.439 nanomoles/4 mm per hour
      after removal of the RPE. At both high (10 mM) and low (50 microM) substrate
      concentrations, lowering of apical potassium was associated with decreased
      transport of taurine across the RPE. For taurine concentrations greater than 42
      microM, the rate-limiting compartment for transport of taurine to the outer
      retina was the RPE monolayer. Similar rates were observed across each compartment
      for concentrations <42 microM. CONCLUSIONS: The magnitude and directionality of
      taurine transport across the RPE is determined solely by the driving taurine
      concentration gradient and is modulated by subretinal levels of potassium. Such
      modulation may provide a mechanism for conserving retinal taurine. Processes that
      increase the resistance to diffusion across Bruch's membrane such as human ageing
      and increased thickening and deposition of debris associated with age-related
      macular degeneration (AMD) are likely to affect transport across the RPE,
      culminating in a secondary retinal taurine deficiency.

PMID- 15505062
TI  - Formulation and evaluation of a predictive model to identify the sites of future
      diabetic retinopathy.
AB  - PURPOSE: To formulate and test a model to predict the development of local
      patches of nonproliferative diabetic retinopathy (NPDR), based on multifocal
      electroretinogram (mfERG) implicit times and candidate diabetic risk factors.
      METHODS: mfERGs and fundus photographs were obtained from 28 eyes of 28 diabetic
      patients during an initial and 12-month follow-up examination. mfERG implicit
      times were derived at 103 locations using a template-stretching method, and a z
      score was calculated in comparison with 20 age-matched normal subjects. Thirty
      five nonoverlapping retinal zones were constructed by grouping two to three
      adjacent stimulated locations, and each zone was assigned the maximum z-score
      within it. Zones containing initial retinopathy were excluded from further
      analysis. The probability that new retinopathy would develop in the remaining
      zones by the follow-up examination was modeled based on the mfERG implicit time z
      score for the zone and other candidate diabetic risk factors determined during
      the initial visit. Data collected from four previously untested diabetic subjects
      and the other eye of eight previous subjects during their second year follow-up
      were used to test the predictive model. RESULTS: After 1 year, new retinopathy
      developed in 11 of the 12 NPDR eyes and 1 of the 16 eyes without initial
      retinopathy. After accounting for the correlation among zones within each eye, a
      predictive model was formulated with the variables mfERG implicit time, duration
      of diabetes, presence of retinopathy (NPDR or no retinopathy), and blood glucose
      level at initial visit. The area under the receiver operating characteristic
      (ROC) curve of this multivariate model is 0.90 (P <0.001). The predictive model
      has an expected sensitivity of 86% and a specificity of 84%, which was verified
      by the test data. CONCLUSIONS: The development of diabetic retinopathy over a 1
      year period can be well predicted by a multivariate model. The inclusion of local
      mfERG implicit times allowed the model to identify the specific sites of future
      retinopathy.

PMID- 15505063
TI  - High TGF-beta2 levels during primary retinal detachment may protect against
      proliferative vitreoretinopathy.
AB  - PURPOSE: Transforming growth factor (TGF)-beta2 and hepatocyte growth factor
      (HGF) have been implicated in the pathogenesis of proliferative vitreoretinopathy
      (PVR) after retinal detachment surgery. The exact role of these factors in the
      early events, immediately after primary retinal detachment, is not yet known, and
      determining their roles was therefore the purpose of this study. METHODS:
      Subretinal fluids were collected prospectively from 144 patients during surgery
      for scleral buckling. TGF-beta2 and HGF were measured with commercially available
      ELISA kits. Thirty patients in whom a redetachment caused by postoperative PVR
      developed, were compared with 114 patients with an uncomplicated retinal
      detachment. The controls included 18 vitreous samples from patients with macular
      hole or pucker. Multivariate regression analysis was used to compare the relative
      roles of growth factors and clinical factors in the development of PVR. RESULTS:
      The median amount of subretinal TGF-beta2 was approximately two times lower in
      patients with postoperative PVR (1.9 ng/mL) than in the uncomplicated detachment
      group (3.3 ng/mL; P=0.002). TGF-beta2 levels in the PVR-positive group were
      similar to control vitreous levels (1.8 ng/mL). Subretinal HGF concentrations
      were not significantly different between the two groups of patients (PVR
      positive: 8.8 ng/mL; PVR negative: 8.9 ng/mL), but were higher than control
      vitreous levels (4.6 ng/mL; P=0.01). Stepwise multivariate logistic regression
      analysis revealed that of all factors under study, decreased TGF-beta2 content
      was the exclusive predictor of postoperative PVR (P=0.01). CONCLUSIONS: High TGF
      beta2 levels in subretinal fluid at the time of primary retinal detachment may
      protect a patient against subsequent development of PVR.

PMID- 15505064
TI  - Comparison of fundus autofluorescence with photopic and scotopic fine-matrix
      mapping in patients with retinitis pigmentosa and normal visual acuity.
AB  - PURPOSE: To compare psychophysically determined spatial variations in photopic
      and scotopic sensitivity across the macula in patients with retinitis pigmentosa
      (RP) and normal visual acuity who manifest an abnormal high-density ring of
      fundus autofluorescence (AF). METHODS: Eleven patients with a clinical diagnosis
      of RP were examined. All had rod-cone dystrophy (International Society for
      Clinical Electrophysiology of Vision [ISCEV]-standard ERGs), visual acuity of 6/9
      or better, and an abnormal parafoveal annulus of high density AF. Fine-matrix
      mapping (FMM) was performed over macular areas of abnormal high-density AF under
      photopic and dark-adapted conditions. Pattern ERGs (PERGs) were performed in 9 of
      11 patients, by using different sizes of circular checkerboards. RESULTS: Rings
      of high-density AF varied between patients (approximately 3 degrees -18 degrees
      in diameter). Photopic sensitivity was preserved over central macular areas, but
      there was a gradient of sensitivity loss over high-density segments of the ring
      and severe threshold elevation outside the arc of the ring. Scotopic sensitivity
      losses were more severe, and they encroached on areas within the ring. The radius
      of the high-density ring correlated with the lateral extent of preserved photopic
      sensitivity (r=0.86) and PERG data. CONCLUSIONS: High-density rings of AF, which
      are present in some patients with RP with normal visual acuity, demarcate areas
      of preserved central photopic sensitivity. Scotopic sensitivity losses encroach
      on areas within the ring of high density and may reflect dysfunction before
      accumulation of lipofuscin.

PMID- 15505065
TI  - Ocular tissue imaging using ultrahigh-resolution, full-field optical coherence
      tomography.
AB  - PURPOSE: Ultrahigh-resolution, full-field optical coherence tomography (OCT),
      which uses a white light source, allows bidimensional, noninvasive tomographic
      imaging without scanning. The goal of the present study was to apply full-field
      OCT to ocular tissue imaging in an attempt to explore the capabilities of the
      technique. METHODS: This full-field OCT system uses a Linnik-type interferometer
      with a tungsten-halogen source. The spatial resolution is 0.9 x 0.7 microm
      (transverse x axial). Unstained tissue samples (cornea, lens, retina, choroid,
      and sclera) and whole, unfixed eyes of rat, mouse, and pig were examined under
      immersion. A charge-coupled device (CCD) camera recorded a pair of
      interferometric images that were combined to display en face (i.e., in the x-y
      plane) tomographic images in real time. The acquisition time per tomographic
      image, which includes summation of 10 raw images, was on the order of 1 s.
      Postprocessing allows volumetric navigation through the image stack as well as
      three-dimensional (3D) imaging. RESULTS: Cellular-level resolution was achieved
      in isolated tissue samples. En face (x-y) images revealed corneal epithelial and
      stromal cells, lens fibers, nerve fibers, major vessels, and retinal pigment
      epithelial cells. In x-z reconstructions, cellular layers within the cornea and
      retina and arterioles and venules were clearly defined. Transscleral retinal
      imaging was achieved in albino animals. CONCLUSIONS: Ultrahigh-resolution, full
      field OCT allows cellular-level imaging of unstained ocular tissues with high
      penetration depth. Although the current system is unsuitable for clinical use,
      this simple technique has potential for in vivo ocular examination, for which a
      new system is currently under development.

PMID- 15505066
TI  - Directed retinal nerve cell growth for use in a retinal prosthesis interface.
AB  - PURPOSE: Retinal prosthetic devices that use microelectrode arrays to stimulate
      retinal nerve cells may provide a viable treatment for degenerative retinal
      diseases. Current devices are based on electrical field-effect stimulation of
      remaining functional neural elements. However, the distance between target
      neurons and electrodes limits the potential density of electrodes and the ability
      to stimulate specific types of retinal neurons that contribute to visual
      perceptions. This study was conducted to investigate the use of microcontact
      printing (muCP) to direct cultured or explant retinal ganglion cell (RGC)
      neurites to precise and close stimulation positions and to evaluate the cell
      types that grow from a retinal explant. METHODS: RGCs and whole retinal explants
      were isolated from postnatal day-7 Sprague-Dawley rats using immunopanning
      purification and microdissection, respectively. Aligned muCP was used to direct
      the growth of RGC neurites from pure cultures (n=105) and retinal explants (n=64)
      along laminin patterns and to individual microelectrodes. Immunofluorescence
      stains (n=39) were used to determine the cell types that grew out from the
      retinal explants. RESULTS: RGC neurite growth was directed reproducibly along
      aligned laminin micropatterns to individual microelectrodes in pure RGC cultures
      and from full-thickness explanted rat retinas in 92% of experiments, neurites
      from pure RGC cultures extended along the laminin lines with an average length of
      263 +/- 118 microm (SD; n=27) after 24 hours. Neurites from retinal explants
      extended in more than 80% of experiments and were observed to grow to an average
      length of 279 +/- 78 microm (n=64) after 2 days in culture. These neurites grew
      up to 3 mm after 1 month of culture on the laminin micropatterns.
      Immunohistochemical stains demonstrated that extended processes from both RGCs
      and glial cells grew out of retinal explants onto stamped laminin lines.
      CONCLUSIONS: Using muCP to pattern surfaces with growth factors, individual
      neuronal processes from pure RGC culture and whole retinal explants can be
      directed to discrete sites on a microelectronic chip surface. By directing RGC
      neurite processes to specific sites, single cell stimulation becomes possible.
      This may allow discrete populations of retinal neurons to be addressed so that
      physiologic retinal processing of visual information can be achieved.

PMID- 15505067
TI  - Characterization of a novel intraocular drug-delivery system using crystalline
      lipid antiviral prodrugs of ganciclovir and cyclic cidofovir.
AB  - PURPOSE: In an earlier study, a novel intraocular drug-delivery system was
      reported in which hexadecyloxypropyl-phospho-ganciclovir (HDP-P-GCV) was used as
      a prototype. The hypothesis was that many biologically effective compounds could
      be modified to crystalline lipid prodrugs and could be delivered directly into
      the vitreous in a long-lasting, slow-release form. This study was undertaken to
      characterize this new drug-delivery system further, by using small particles of
      HDP-P-GCV and hexadecyloxypropyl-cyclic cidofovir (HDP-cCDV). METHODS: HDP-P-GCV
      was microfluidized into 4.4-microm (median) particles, injected into rabbit
      vitreous. The vitreous drug level was then measured at different time points.
      Crystalline HDP-cCDV was synthesized, suspended in 5% dextrose, and injected into
      the rabbit's vitreous at 10, 55, 100, 550, or 1000 microg in 50 microL vehicle
      per eye, to determine the highest nontoxic dose. The dose, 100 microg, was
      injected into 24 rabbit eyes, to evaluate pharmacokinetics; into 14 rabbit eyes
      with established HSV retinitis, to evaluate its efficacy; and into 58 rabbit eyes
      before herpes simplex virus (HSV) infection to evaluate its intraocular antiviral
      duration. RESULTS: Microfluidized particles of HDP-P-GCV showed an increased drug
      release rate compared with the large-particle drug formulation, with area under
      concentration-time curve (AUC) of 219.8 +/- 114.1 (n=3) versus 108.3 +/- 47.2
      (n=3) for unmodified HDP-P-GCV during the 12-week period after a 2.8-micromole
      intravitreal injection. There was a 103% increase of the drug released from the
      microfluidized formulation of HDP-P-GCV versus the unmodified formulation.
      Intravitreal injections of HDP-cCDV at doses of 100 microg/eye or lower were not
      toxic. After the 100 microg/eye injections, HPLC analysis showed a vitreous HDP
      cCDV level of 0.05 microM at week 5, which declined to 0.002 microM at week 8.
      The concentration at week 8 (0.002 microM) remained above the IC50 for
      cytomegalovirus (0.0003 microM). The pretreatment study demonstrated an antiviral
      effect that lasted 100 days after a single intravitreal injection. CONCLUSIONS:
      This crystalline lipid prodrug intravitreal delivery system is an effective
      approach to achieving sustained, therapeutic drug levels in the eye. Small
      microfluidized particles of HDP-P-GCV provide more rapid dissolution and higher
      vitreous drug levels.

PMID- 15505068
TI  - The anti-thyroid drug methimazole induces neovascularization in the neonatal rat
      analogous to ROP.
AB  - PURPOSE: To determine the effect of methimazole (MMI), an anti-thyroid drug known
      to reduce serum l-thyroxine (T4), and insulin-like growth factor (IGF)-1
      concentrations, on retinal vascular development in neonatal rats. METHODS:
      Sprague-Dawley rats (n=175) were raised in expanded litters of 25 in room air and
      were exposed to MMI from birth (given as a 0.1% solution to nursing mothers for
      either 4 or 10 days). Experiments ended on day 4 (n=25) or 10 (n=50) of life. A
      third group was exposed to MMI for the initial 4 days of life and then allowed to
      recover for the next 6 days (n=50). Fifty control rats were analyzed on day 4
      (n=25) or 10 (n=25) of life. Left eyes were fixed, and retinas were dissected and
      stained with adenosine diphosphatase (ADPase). Retinas were graded for presence
      and severity of neovascularization (NV) in a masked manner, and retinal vascular
      areas were quantified. In a subsequent study, serum IGF-1 and T4 levels were
      measured by radioimmunoassay in an additional 200 rats exposed to treatments
      identical to those described. RESULTS: Retinal NV occurred in 31% of rats exposed
      to 10 days of MMI and 4% (P=0.02) of rats exposed to 4 days of MMI, followed by 6
      days of recovery. None of the rats exposed to 4 days of MMI alone and none of the
      control animals was graded positive for NV. Retinal vascular areas were
      significantly reduced in rats exposed to 4 days of MMI compared with 4-day
      control animals (36% +/- 6% vs. 50% +/- 6%, P=0.0001). Serum IGF-1 levels were
      markedly reduced in 4-day MMI rats compared with age-matched control animals (42
      ng/mL vs. 133 ng/mL, P=0.0001) and in 10-day MMI rats compared with 10-day
      control animals (133 ng/mL vs. 206.5 ng/mL, P=0.005). Serum T4 levels were
      similarly suppressed in the MMI-exposed litters compared with control animals at
      day 10 (P=0.008). In contrast, rats exposed to 4 days of MMI followed by 6 days
      of recovery had normal serum IGF-1 and T4 levels by day 10. CONCLUSIONS: The anti
      thyroid drug, MMI, induces NV in neonatal rats. This may be mediated by the
      initial suppression of serum IGF-1. Nevertheless, the lower incidence of NV when
      serum IGF-1 levels are initially suppressed followed by complete recovery, is
      contrary to a purely permissive role for serum IGF-1, as reported previously. The
      relationship between the temporal course of serum IGF-1 and NV in immature
      retinas needs further investigation.

PMID- 15505069
TI  - Outcome of transplantation of autologous retinal pigment epithelium in age
      related macular degeneration: a prospective trial.
AB  - PURPOSE: To present the outcome of a consecutive series of patients who had
      foveal choroidal neovascularization (fCNV) in age-related macular degeneration
      (AMD) and were treated with subretinal surgery combined with simultaneous
      transplantation of autologous retinal pigment epithelial (RPE) cells. METHODS:
      Patients with fCNV who were not eligible for laser or photodynamic therapy were
      included in the study. They underwent subretinal membrane excision with
      simultaneous transplantation of autologous RPE cells. Eyes with membrane excision
      alone served as the control. Tests included best corrected visual acuity for far
      and near with Early Treatment Diabetic Retinopathy Study (ETDRS) and Jaeger
      charts, multifocal (mf)ERG, central visual field analysis, optical coherence
      tomography (OCT), and angiography, before surgery, and 1 month and 3 months after
      treatment, and at 3-month intervals thereafter. RESULTS: The results of final
      examinations of 53 eyes are presented. In 39 eyes, RPE transplantation was
      performed (group 1); 14 eyes had membrane excision alone (group 2). In group 1,
      visual acuity improved significantly, two or more lines in 21 (53.8%) patients;
      remained stable in 12 patients (30.8%); and decreased two or more lines in 6
      patients (15.4%; P=0.0062). In group 2, the corresponding values were 21.1%,
      57.8%, and 21.1% (P=0.5377 NS). Statistical analysis of results in the two groups
      showed a trend in favor of group 1 (P=0.9714). The difference in reading acuity
      was significant between the two groups (mean change in group 1: 1.85 +/- 0.42 vs.
      0.43 +/- 0.47 in group 2; P=0.0001). mfERG response density changes were
      significantly different between groups 1 and 2 (P=0.0094). No significant
      decreases in central visual field defects were detected. OCT showed the
      postoperative median retinal thickness in the lesion area in group 1 to be higher
      (242.31 +/- 12.30 microm) than in group 2 (202.07 +/- 10.68 microm), showing a
      trend (P=0.0682). CONCLUSIONS: Patients undergoing fCNV removal with autologous
      transplantation of RPE reached significantly better reading acuity and higher
      mfERG-response density than control subjects. The results provide evidence that
      autologous transplantation of RPE is a beneficial supplement to membrane excision
      alone in patients with fCNV in AMD and may be regarded as a reasonable treatment
      option.

PMID- 15505070
TI  - Role of interleukin-1beta in the development of retinopathy in rats: effect of
      antioxidants.
AB  - PURPOSE: Diabetic retinopathy is shown to share many similarities with chronic
      inflammatory disease, and in diabetes, accelerated apoptosis of retinal capillary
      cells is evident before histopathology can be seen. The purpose of this study was
      to examine the effect of interleukin (IL)-1beta on capillary cell apoptosis in
      rat retina and to determine the effect of antioxidants on diabetes-induced
      changes in retinal IL-1beta. METHODS: The effect of injection of IL-1beta into
      the vitreous (5 ng/5 microL) of normal rats on capillary cell apoptosis (detected
      by terminal transferase dUTP nick-end labeling [TUNEL]) and formation of
      acellular capillaries was investigated in the trypsin digested retinal
      microvessels. The levels of IL-1beta were quantified (by ELISA and Western blot)
      in the retina of rats diabetic for 2 months, and the effect of administration of
      antioxidants on diabetes-induced changes in retinal IL-1beta was determined.
      RESULTS: The number of TUNEL-positive capillary cells in the retinal microvessels
      obtained from normal rats that received intravitreal injection of IL-1beta was
      increased by more than threefold and that of acellular capillaries by more than
      twofold, compared with the microvessels obtained from rats that received an
      intravitreal injection of PBS (5 microL) or BSA (5 ng/5 microL). IL-1beta also
      increased the levels of 8-hydroxy-2'-deoxyguanosine (an indicator of oxidative
      stress) and nitric oxide by more than 40% and activated NF-kappaB by 35% to 55%.
      Two months of diabetes in rats increased retinal IL-1beta levels by more than
      twofold, and antioxidants inhibited such increases. CONCLUSIONS: IL-1beta, by
      activation of NF-kappaB and an increase in oxidative stress, plays an important
      role in the retinal microvascular disease that is characteristic of diabetic
      retinopathy. Antioxidants inhibit diabetes-induced increases in retinal IL-1beta.
      These studies offer a possible rationale to test IL-1beta-targeted therapies to
      inhibit the development of retinopathy in diabetes.

PMID- 15505071
TI  - Multipotent retinal progenitors express developmental markers, differentiate into
      retinal neurons, and preserve light-mediated behavior.
AB  - PURPOSE: To use progenitor cells isolated from the neural retina for
      transplantation studies in mice with retinal degeneration. METHODS: Retinal
      progenitor cells from postnatal day 1 green fluorescent protein-transgenic mice
      were isolated and characterized. These cells can be expanded greatly in culture
      and express markers characteristic of neural progenitor cells and/or retinal
      development. RESULTS: After they were grafted to the degenerating retina of
      mature mice, a subset of the retinal progenitor cells developed into mature
      neurons, including presumptive photoreceptors expressing recoverin, rhodopsin, or
      cone opsin. In rho-/- hosts, there was rescue of cells in the outer nuclear layer
      (ONL), along with widespread integration of donor cells into the inner retina,
      and recipient mice showed improved light-mediated behavior compared with control
      animals. CONCLUSIONS: These findings have implications for the treatment of
      retinal degeneration, in which neuronal replacement and photoreceptor rescue are
      major therapeutic goals.

PMID- 15505072
TI  - Neuroprotective effect of hepatocyte growth factor against photoreceptor
      degeneration in rats.
AB  - PURPOSE: To determine whether hepatocyte growth factor (HGF) has a
      neuroprotective effect against photoreceptor degeneration in rats. METHODS: Eight
      week-old Sprague-Dawley (SD) and 24-day-old Royal College of Surgeons (RCS) rats
      received an intravitreal injection of HGF in the right eyes. The left eyes were
      injected with vehicle and served as the control. Two days after the injections,
      the SD rats were exposed to fluorescent light of 3000 lux for 72 hours. Scotopic
      and photopic electroretinograms (ERGs) were recorded 2 weeks after the light
      damage and at 70 days of age in RCS rats. After the ERG recordings, the animals
      were killed for histologic analysis. Some RCS rats were killed at 2 weeks after
      HGF-treatment for TdT-dUTP terminal nick-end labeling (TUNEL) studies. RESULTS:
      In both light-damaged and RCS rats, the thresholds for the scotopic and photopic
      b-wave were significantly lower in the HGF-treated eyes than in the control eyes
      (P <0.02). The maximum b-wave amplitudes (Vbmax) of the scotopic and photopic
      ERGs were significantly larger in the HGF-treated eyes (P <0.0005) with a
      significantly greater number of photoreceptor nuclei than in the control eyes in
      both animal models (P <0.005). The vehicle-injected eyes of RCS rats had
      significantly larger numbers of TUNEL-positive photoreceptor nuclei than the HGF
      treated eyes (P=0.005). CONCLUSIONS: Intravitreal HGF led to the morphologic and
      physiological preservation of photoreceptors in rats with photoreceptor
      degeneration induced by phototoxicity or a gene mutation. The antiapoptotic
      effect may be the mechanism for the neuroprotective action of HGF.

PMID- 15505073
TI  - Cysteine starvation activates the redox-dependent mitochondrial permeability
      transition in retinal pigment epithelial cells.
AB  - PURPOSE: Glutathione (GSH) plays a key role in protection against oxidative
      stress. L-cysteine is thought to be rate-limiting for the synthesis of
      glutathione (GSH) and therefore may be a critical component in protection against
      oxidative stress. The purpose of this study was to investigate the role of L
      cysteine in GSH metabolism and oxidative stress in human retinal pigment
      epithelial (hRPE) cells. METHODS: To identify the role of cysteine in GSH
      metabolism in hRPE cells, a strategy of cysteine starvation was used to determine
      (1) GSH levels and oxidative stress by measuring reactive oxygen species (ROS)
      production, (2) mitochondrial membrane potential (Deltapsim) and mitochondrial
      ultrastructure by using conventional electron microscopy (EM), and (3) indices of
      cell viability and apoptosis including analysis of cells containing hypodiploid
      amounts of DNA. RESULTS: Cysteine starvation resulted in approximately a 95%
      decrease in GSH concentrations over 24 hours. The GSH Nernst redox potential (Eh)
      increased approximately 70 mV (Eh=-248 +/- 2.9 mV in control cells compared with
      Eh=-179 +/- 2.0 mV in cysteine-starved cells) indicating significant
      intracellular oxidation. Cysteine starvation increased the production of ROS by
      mitochondrial respiratory complex III (cytochrome bc1), determined using a
      pharmacological strategy that resulted in the loss of Deltapsim and cell death.
      The loss of Deltapsim and cell death was prevented with bongkrekic acid, an
      inhibitor of the adenine nucleotide translocator inhibitor, suggesting activation
      of the mitochondrial permeability transition (MPT). This conclusion was further
      supported by electron microscopic studies that showed significant mitochondrial
      swelling, a hallmark of MPT activation. Cell death was not prevented with either
      the broad-spectrum caspase inhibitor zVADfmk or the caspase 3-specific inhibitor
      DEVD-CHO, indicating that cytochrome bc1-mediated ROS production results in the
      MPT and necrosis. CONCLUSIONS: These results show that cysteine is a required
      component for normal GSH metabolism and protection against oxidative stress in
      hRPE cells.

PMID- 15505074
TI  - BDNF reduces the retinal toxicity of verteporfin photodynamic therapy.
AB  - PURPOSE: Verteporfin photodynamic therapy (PDT) is the most effective treatment
      for age-related macular degeneration, using laser activation of a
      photosensitizing dye to achieve closure of choroidal neovascularization. Although
      PDT preferentially affects pathologic vessels, it can also cause collateral
      damage to the overlying retina. In the current study, it was found that the
      neuroprotective agent brain-derived neurotrophic factor (BDNF) reduces this
      retinal damage. METHODS: Normal adult rats received intravitreal BDNF in one eye
      and PBS or no injection in the other eye 2 days before PDT. RESULTS: Control eyes
      exhibited choroidal hypofluorescence, moderate to severe photoreceptor loss, and
      depression of local retinal function measured using multifocal ERG in the laser
      treated area. BDNF-injected eyes had more surviving photoreceptors and improved
      multifocal ERG responses 1 week after PDT. BDNF did not diminish the effect of
      PDT on the choroidal circulation as assessed by fluorescein angiography, and
      there was no evidence of retinal toxicity due to BDNF treatment. CONCLUSIONS:
      These results suggest that adjunctive neuroprotective therapy may reduce
      collateral damage to photoreceptors and improve visual outcome after PDT.

PMID- 15505075
TI  - In vivo three-dimensional evaluation of leukocyte behavior in retinal
      microcirculation of mice.
AB  - PURPOSE: To evaluate new physiologic and three-dimensional methods for monitoring
      leukocyte behavior in mouse retina. METHODS: Endotoxin-induced uveitis (EIU) was
      produced in mice by footpad injection of lipopolysaccharide (LPS). Leukocytes
      were labeled with acridine orange (AO). Leukocyte rolling in the retinal
      microcirculation was evaluated in vivo with AO digital fluorography. The number
      of migrated leukocytes was counted in flatmounted retina. The behavior of
      leukocyte migration was observed three-dimensionally at the time of peak
      migration. After leukocytes were labeled with AO, the mice were perfused with
      rhodamine-labeled concanavalin A lectin to stain the vascular endothelium.
      Leukocyte migration into the retina was then monitored three-dimensionally with
      confocal microscopy, and the velocity of the migration was measured. RESULTS:
      Both leukocyte rolling and migration peaked at 48 hours after LPS injection.
      Leukocytes were seen to extravasate from the deeper capillary layers and to
      migrate toward the outer layer of the retina. The traveling velocity of
      extravasated leukocytes in retinal tissue was 2.0 +/- 0.1 microm/h. CONCLUSIONS:
      New methods have been demonstrated for the three-dimensional and quantitative
      evaluation of leukocyte behavior in mouse retina.

PMID- 15505076
TI  - Melanopsin is expressed in PACAP-containing retinal ganglion cells of the human
      retinohypothalamic tract.
AB  - PURPOSE: The putative circadian photoreceptor melanopsin is found in rodents in a
      subpopulation of intrinsic light-sensitive retinal ganglion cells (RGCs)
      constituting the retinohypothalamic tract (RHT). The study was conducted to
      determine whether melanopsin is expressed in the human retina and costored with
      the neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP), a
      marker for the RHT, projecting to the suprachiasmatic nucleus (SCN). Furthermore,
      whether melanopsin expression is conserved in retinas of blind patients with
      severe retinal degeneration was investigated. METHODS: In situ hybridization and
      immunohistochemistry was used to demonstrate melanopsin synthesis in human eyes
      of 17 donors and two postmortem hypothalami containing the SCN. The coexistence
      of melanopsin and PACAP in elements of the retinohypothalamic tract was studied
      by dual-labeling immunocytochemistry. RESULTS: Melanopsin expression was found in
      a subpopulation of RGCs located in the ganglion cell layer and displaced in the
      inner nuclear cell layer. Melanopsin-containing cells comprised approximately 0.
      8% of all RGCs, with a distinct morphology characterized by two to four dendritic
      processes constituting a panretinal network. Melanopsin immunoreactivity was
      primary present at perikaryal boundaries and neuronal processes and to some
      extent also in the cytoplasm. PACAP and melanopsin were colocalized in the RGCs
      and PACAP-containing nerve fibers, seemingly innervating the retinorecipient part
      of the SCN. Melanopsin-expressing RGCs were conserved in retinas of blind
      patients with severe degeneration of the outer and/or inner layers. CONCLUSIONS:
      Given the expression of melanopsin in PACAP-containing RGCs of the human RHT,
      this photoreceptor is a likely first base in the chain of events leading to
      photoentrainment of both normal and blind people.

PMID- 15505077
TI  - Retinal pigment epithelial cell behavior is modulated by alterations in focal
      cell-substrate contacts.
AB  - PURPOSE: To investigate how the cellular behavior of cultured retinal pigment
      epithelial (RPE) cells was affected by the manipulation of early focal contact.
      METHODS: To manipulate early focal contact, a reduced focal cell-substrate
      contact area on the micropatterned surfaces was implemented by microfabrication
      with polydimethylsiloxane (PDMS). The micropatterned PDMS surfaces had a circular
      pillar with a diameter of 5 microm. The human retinal pigment epithelial cell
      line, ARPE-19, was seeded onto the fibronectin-coated PDMS surfaces. Cell
      adhesion, growth, cell cycle, morphology, and interleukin-6 (IL-6) expression
      were observed for 3 weeks. RESULTS: The fluorescent images of localized vinculin
      and actin stress fibers appeared to be more prominent on smooth PDMS surfaces.
      Although there was no significant effect on cell adhesion, a statistically
      significant inhibition of cell cycle progression was observed for micropatterned
      PDMS surfaces. Similarly, micropatterned surfaces showed significantly less cell
      growth than that of smooth surfaces. Cultures over a period of 3 weeks showed a
      distinct cell-cell phenotype discrepancy. Furthermore, IL-6 mRNA and secreted
      protein induced by IL-1beta in ARPE-19 were downregulated on micropatterned PDMS
      surfaces. CONCLUSIONS: Disturbed focal contact in ARPE-19 cells grown on
      micropatterned surfaces altered cell cycle, growth, morphology, and the
      expression of IL-6 in vitro.

PMID- 15505078
TI  - OPA1, the disease gene for autosomal dominant optic atrophy, is specifically
      expressed in ganglion cells and intrinsic neurons of the retina.
AB  - PURPOSE: Autosomal dominant optic atrophy is a hereditary disorder characterized
      by progressive loss of vision and caused by mutations in a dynamin-related gene,
      OPA1, which translates into a protein with a mitochondrial leader sequence. In
      this study the OPA1 gene and its protein were localized in the rat and mouse
      retina, and its rat orthologue, rOpa1, was identified. METHODS: The rOpa1 cDNA
      was isolated by using reverse transcribed cDNA from total RNA obtained from a rat
      retinal ganglion cell line. The spatial and temporal expression patterns of OPA1
      and its gene product were investigated by RNA in situ hybridization and
      immunohistochemistry in mouse and rat retinas. To characterize further the OPA1
      positive neurons, retinal ganglion cells were retrogradely labeled by an
      immunogold fluorescent tracer or double labeled with OPA1 and choline
      acetyltransferase or calbindin antibodies. RESULTS: Protein sequence alignment
      revealed a 96% identity between rat and human OPA1 mRNA. OPA1 expression was
      found as early as postnatal day 3 in the developing rodent retina. In the mature
      retina, the OPA1 gene and its protein were found not only in retinal ganglion
      cells, but also in starburst amacrine cells and horizontal cells, both of which
      are involved in lateral signal processing within the retina. However, OPA1 was
      absent from mitochondria rich nerve fibers and photoreceptor indicating a
      specific role for OPA1 in signal processing rather than in the requirement of
      mitochondrial energy supply in the retina. CONCLUSIONS: The data suggest an
      important and specific function of the OPA1 protein, not only in the optic nerve
      forming ganglion cells but also in the intrinsic signal processing of the inner
      retina.

PMID- 15505079
TI  - Heme oxygenase-1 induced in muller cells plays a protective role in retinal
      ischemia-reperfusion injury in rats.
AB  - PURPOSE: To investigate the protective roles played by heme oxygenase (HO)-1 and 
      2 in the rat retina after ischemia-reperfusion injury. METHODS: Retinal ischemia
      was induced in rats by increasing the intraocular pressure to 110 mmHg for 60
      minutes. The expression of HO-1 and -2 in the retina was determined by Western
      blot, real-time polymerase chain reaction (PCR), and immunohistochemistry. To
      inhibit the upregulation of HO-1, short interfering (si)RNA of HO-1 was injected
      intravitreally before ischemia and that of green fluorescent protein (GFP) was
      used as the control. Muller cell damage was assessed by counting the number of S
      100-positive cells. The number of macrophages invading the retina was determined
      by counting the number of ED-1-positive cells. RESULTS: The expression of HO-1
      mRNA and protein was upregulated at 6 hours after reperfusion and peaked at 12 to
      24 hours, whereas that of HO-2 was not altered. HO-1 immunoreactivities were
      detected in Muller cells at 24 hours after reperfusion, and HO-2
      immunoreactivities were detected in retinal cells. The HO-1 expression in the
      retina treated with siRNA of HO-1 was reduced at 12 and 24 hours after
      reperfusion compared with that injected with siRNA of GFP. The number of S-100
      positive cells at 24 hours after reperfusion decreased significantly in retinas
      treated with HO-1 siRNA (P <0.01). The number of macrophages that had infiltrated
      the retina was increased in retinas pretreated with the siRNA of HO-1 compared
      with those treated with siRNA of GFP. On day 14 after reperfusion, HO-1 siRNA
      treated retinas showed severe retinal injury and destruction of the retinal
      architecture. CONCLUSIONS: HO-1 promotes the survival of Muller cells after
      ischemia-reperfusion injury. Because inhibition of the upregulation of HO-1
      resulted in an infiltration of inflammatory cells and destruction of the retina,
      the authors conclude that HO-1 induced in Muller cells plays a protective role in
      retinal ischemia-reperfusion.

PMID- 15505080
TI  - Interrelations between brachial endothelial function and carotid intima-media
      thickness in young adults: the cardiovascular risk in young Finns study.
AB  - BACKGROUND: Endothelial vasodilator dysfunction and carotid intima-media
      thickening (IMT) are 2 indicators of subclinical cardiovascular disease. We
      examined their correlation and interaction with risk factors in a large,
      community-based cohort of young adults. METHODS AND RESULTS: As part of the
      longitudinal Cardiovascular Risk in Young Finns Study, we measured endothelium
      dependent brachial artery flow-mediated dilatation (FMD) and carotid artery IMT
      by ultrasound in 2109 healthy adults aged 24 to 39 years. FMD was inversely
      associated with IMT (P< or =0.001) in a multivariate model adjusted for age, sex,
      brachial vessel size, and several risk variables. The subjects with age- and sex
      specific FMD values in the extreme deciles were classified into groups of
      impaired (n=204, FMD=1.1+/-1.4%, mean+/-SD) and enhanced (n=204, FMD=16.3+/-2.9%)
      FMD response. The number of risk factors was correlated with increased IMT in
      subjects with an impaired FMD response (P<0.05) but not in subjects with an
      enhanced FMD response (P>0.2). CONCLUSIONS: Brachial FMD is inversely associated
      with carotid IMT. The number of risk factors in young adults is correlated with
      increased IMT in subjects with evidence of endothelial dysfunction, but not in
      subjects with preserved endothelial function. These observations suggest that
      endothelial dysfunction is an early event in atherosclerosis and that the status
      of systemic endothelial function may modify the association between risk factors
      and atherosclerosis.

PMID- 15505081
TI  - Heart rate recovery and impact of myocardial revascularization on long-term
      mortality.
AB  - BACKGROUND: Although heart rate recovery (HRR) predicts mortality after exercise
      testing, its ability to identify patients likely to benefit after
      revascularization is unknown. We sought to determine whether HRR can identify
      patients likely to have improved survival after revascularization. METHODS AND
      RESULTS: A total of 8861 patients undergoing treadmill nuclear or
      echocardiographic testing were divided into early revascularization (percutaneous
      coronary intervention or bypass surgery within 3 months) and non-early
      revascularization groups. Prespecified subgroup analysis was performed based on
      the presence or absence of ischemia, normal or impaired functional capacity, and
      normal or abnormal HRR. The primary end point was all-cause mortality. Early
      revascularization occurred in 552 patients. We propensity-matched 508 early
      revascularization patients to 508 non-early revascularization patients on the
      basis of 48 possible confounders. This constituted the present study cohort.
      During 8-year follow-up, 232 patients died. Overall, revascularization was
      associated with a slight but not significant decrease in mortality (hazard ratio
      [HR] 0.80, 95% CI 0.62 to 1.03). A significant decrease in mortality after
      revascularization was present in patients with imaging evidence of stress-induced
      ischemia (HR 0.62, 95% CI 0.44 to 0.87). Ischemic patients with normal HRR had
      significantly lower mortality with revascularization (HR 0.55, 95% CI 0.34 to
      0.90), whereas ischemic patients with abnormal HRR did not (HR 0.78, 95% CI 0.47
      to 1.29); however, the test for interaction between these 2 groups was not
      significant (P=0.34). CONCLUSIONS: In patients with imaging evidence of
      myocardial ischemia, an abnormal HRR is associated with a nonsignificant trend
      toward blunting the survival improvement associated with early revascularization.
      HRR does not appear to identify patients likely to have a survival benefit.

PMID- 15505082
TI  - Comparison of late luminal loss response pattern after sirolimus-eluting stent
      implantation or conventional stenting.
AB  - BACKGROUND: We investigated the pattern of late luminal loss after sirolimus
      eluting or bare stent implantation. METHODS AND RESULTS: The study population
      comprised 238 patients treated with sirolimus-eluting stents and 526 patients
      treated with conventional stents. The distribution of late loss of sirolimus
      stents was largely skewed to the right and differed from the distribution for
      bare stents. When divided according to the presence of binary restenosis
      (diameter stenosis >50%), restenotic lesions in the bare stent group (26.0%) had
      a late loss of 1.40+/-0.64 mm and in the sirolimus group (7.9%) of 1.16+/-0.76
      mm. Nonrestenotic lesions in the bare stent group had a late loss of 0.58+/-0.44
      mm, whereas the late loss of nonrestenotic lesions in the sirolimus group
      remained close to zero (-0.05+/-0.33 mm). Differences between poststenting and
      follow-up measurements in the sirolimus group (late loss) resembled variations
      observed in repeated angiographic measurements, as assessed from a random sample
      of 30 segments measured repeatedly. After multivariate adjustment, stent type did
      not influence the degree of late loss in restenotic lesions. However,
      nonrestenotic bare stents had a significantly larger estimated luminal loss (0.58
      mm; 95% CI, 0.52 to 0.65) than sirolimus-eluting stents, for which the predicted
      late loss was almost 0 (-0.04 mm; 95% CI, -0.10 to 0.02). CONCLUSIONS: The
      pattern of late loss after sirolimus-eluting stent implantation follows a
      peculiar behavior, different from lesions treated with conventional stents.
      Whether this is explained by an unusual statistical distribution or a biological
      all-or-none response of restenosis after sirolimus-eluting stenting remains to be
      investigated.

PMID- 15505084
TI  - Radiation exposure during catheter ablation of atrial fibrillation.
AB  - BACKGROUND: The purpose of this study was to determine the radiation exposure
      during catheter ablation of atrial fibrillation (AF) using the pulmonary vein
      (PV) approach. METHODS AND RESULTS: The study included 15 patients with AF and 5
      patients each with atrial flutter and atrioventricular nodal reentrant
      tachycardia (AVNRT) who underwent fluoroscopically guided procedures on a biplane
      x-ray system operated at a low-frame pulsed fluoroscopy (7.5 frames per second).
      Radiation exposure was measured directly with 50 to 60 thermoluminescent
      dosimeters (TLDs). Peak skin doses (PSDs), effective radiation doses, and risk of
      fatal malignancies were all computed. Mean fluoroscopy durations for AF
      procedures were 67.8+/-21 minutes in the right anterior oblique (RAO) and 61.9+/
      16.6 minutes in the left anterior oblique (LAO) projection, significantly
      different from that required for atrial flutter and AVNRT. The mean PSDs measured
      with the TLDs were 1.0+/-0.5 Gy in the RAO and 1.5+/-0.4 Gy in the LAO
      projection. The lifetime risk of excess fatal malignancies normalized to 60
      minutes of fluoroscopy was 0.07% for women and 0.1% for men. CONCLUSIONS: The
      relatively small amounts of the patient's radiation exposure in this study,
      despite the prolonged fluoroscopy durations, can be attributed to the use of very
      low-frame pulsed fluoroscopy, the avoidance of magnification, and optimal
      adjustments of the fluoroscopy exposure rates. The resulting lifetime risk of
      fatal malignancy is within the range previously reported for standard
      supraventricular arrhythmias.

PMID- 15505083
TI  - Rate dependence and regulation of action potential and calcium transient in a
      canine cardiac ventricular cell model.
AB  - BACKGROUND: Computational biology is a powerful tool for elucidating
      arrhythmogenic mechanisms at the cellular level, where complex interactions
      between ionic processes determine behavior. A novel theoretical model of the
      canine ventricular epicardial action potential and calcium cycling was developed
      and used to investigate ionic mechanisms underlying Ca2+ transient (CaT) and
      action potential duration (APD) rate dependence. METHODS AND RESULTS: The
      Ca2+/calmodulin-dependent protein kinase (CaMKII) regulatory pathway was
      integrated into the model, which included a novel Ca2+-release formulation, Ca2+
      subspace, dynamic chloride handling, and formulations for major ion currents
      based on canine ventricular data. Decreasing pacing cycle length from 8000 to 300
      ms shortened APD primarily because of I(Ca(L)) reduction, with additional
      contributions from I(to1), I(NaK), and late I(Na). CaT amplitude increased as
      cycle length decreased from 8000 to 500 ms. This positive rate-dependent property
      depended on CaMKII activity. CONCLUSIONS: CaMKII is an important determinant of
      the rate dependence of CaT but not of APD, which depends on ion-channel kinetics.
      The model of CaMKII regulation may serve as a paradigm for modeling effects of
      other regulatory pathways on cell function.

PMID- 15505085
TI  - Analysis of catheter-tip (8-mm) and actual tissue temperatures achieved during
      radiofrequency ablation at the orifice of the pulmonary vein.
AB  - BACKGROUND: Many ablative approaches in or near the orifice of the pulmonary vein
      (PV) have demonstrated success in eliminating atrial fibrillation. Despite
      current practice, there are no data regarding the in vivo efficacy and safety of
      an 8-mm catheter tip for ablation at the PV orifice. METHODS AND RESULTS: Ten
      mongrel dogs were studied. Thermocouples were implanted in the atrial muscle of
      the PV orifice. Intracardiac echocardiography monitored catheter position,
      tip/tissue orientation, and microbubble formation. Ninety-four ablations were
      performed for 120 seconds. A temperature discrepancy >10 degrees C between the
      catheter tip and tissue occurred during 47 (50%) of the ablations. Despite
      termination of energy delivery, the average tissue temperature remained within 1
      degrees C of the achieved steady state for 9 seconds. A temperature discrepancy
      >10 degrees C was more common in the right superior PV, with oblique catheter
      positioning, when tissue temperatures were >60 degrees C or 80 degrees C, and
      with type 1 or type 2 microbubble formation. However, microbubbles were not
      present in 7 (13%, type 1) and 10 (40%, type 2) ablations with tissue
      temperatures >80 degrees C. The maximum tissue temperature achieved with non-full
      thickness lesions was 47.3+/-7.4 degrees C vs 75.9+/-11.7 degrees C (P<0.0001)
      for full-thickness lesions. CONCLUSIONS: Marked discrepancies between catheter
      tip and tissue temperatures occurred with higher temperatures, prolonged ablation
      times, and unfavorable catheter thermistor-tissue contact. Also, these data
      suggest a conservative approach to atrial ablation, because full-thickness
      lesions were obtained when tissue temperatures reached 50 degrees C to 60 degrees
      C and the tissue retained high heat levels despite termination of radiofrequency
      energy. Finally, microbubbles are inconsistent markers of tissue overheating.

PMID- 15505086
TI  - Percutaneous mitral annular reduction provides continued benefit in an ovine
      model of dilated cardiomyopathy.
AB  - BACKGROUND: Functional mitral valve regurgitation plays a key role in the
      symptomatic severity and progression of heart failure. In an ovine model of
      dilated cardiomyopathy, we examined the chronic functional consequences of mitral
      regurgitation reduction using a recently developed novel percutaneous mitral
      annular reduction (PMAR) device. METHODS AND RESULTS: Fourteen adult sheep were
      paced right ventricularly at 180 to 190 bpm for 5 weeks, leading to the
      development of moderate mitral valve regurgitation. After echocardiographic,
      hemodynamic, and neurohormonal analysis, 9 animals underwent PMAR. All animals
      were subsequently paced for another 28 days, and a final echocardiographic and
      hemodynamic study was conducted. Animals that had undergone PMAR showed
      significantly increased negative and positive dP/dt, whereas pulmonary capillary
      wedge pressure and mitral valve regurgitation were significantly reduced compared
      with those at device implant despite continued pacing. In conjunction,
      significant improvements in plasma norepinephrine and brain natriuretic peptide
      were apparent. CONCLUSIONS: The application of PMAR in animals with pacing
      induced dilated cardiomyopathy and functional mitral valve regurgitation resulted
      in continued improvements in hemodynamic and neurohormonal parameters.

PMID- 15505087
TI  - Balanced regulation of mRNA production for Fas and Fas ligand in lymphocytes from
      centenarians: how the immune system starts its second century.
AB  - BACKGROUND: The functionality of the immune system during aging is crucial for
      protection against the most common age-related diseases. Apoptosis plays a
      central role in the senescence of the immune system, as evidenced by the
      increased plasma membrane expression of a key molecule like Fas protein. We
      analyzed the mRNA levels of different forms of Fas (total [tFas] and membrane
      [mFas]) and of its ligand (FasL) in peripheral blood lymphocytes from
      centenarians, the best example of successful aging, who were compared with young
      and middle-aged donors. METHODS AND RESULTS: Using real-time polymerase chain
      reaction, we quantified mRNA for different forms of Fas and for FasL. In resting
      lymphocytes, mRNA for tFas, but not for mFas, significantly increases with age,
      whereas FasL mRNA significantly decreases. In vitro production of Fas/FasL mRNA
      after different stimuli was similar in cells from the 3 groups. Even if the
      percentage of Fas+ cells was higher than in the other groups, peripheral blood
      lymphocytes from centenarians had normal Fas-induced apoptosis, as revealed by
      flow cytometry. By ELISA, we observed that cells from centenarians showed normal
      in vitro production of the soluble form of Fas (sFas) and that plasma levels of
      such molecule were significantly higher in centenarians than in the other groups.
      CONCLUSIONS: Lymphocytes from centenarians are able to balance the production of
      proapoptotic (mFas and FasL) and antiapoptotic (sFas) molecules, whose
      proportions are likely crucial for the well-preserved immune functionality at the
      extreme limits of human life.

PMID- 15505088
TI  - Low-density lipoprotein triglycerides associated with low-grade systemic
      inflammation, adhesion molecules, and angiographic coronary artery disease: the
      Ludwigshafen Risk and Cardiovascular Health study.
AB  - BACKGROUND: Markers of systemic inflammation and LDL cholesterol (LDL-C) have
      been considered independent risk factors of coronary artery disease (CAD). We
      examined whether alterations of LDL metabolism not reflected by LDL-C were
      associated with low-grade inflammation, vascular injury, and CAD. METHODS AND
      RESULTS: We studied 739 subjects with stable angiographic CAD and 570 matched
      control subjects in which CAD had been ruled out by angiography. The association
      of LDL triglycerides (LDL-TGs) (odds ratio [OR], 1.30; 95% CI, 1.19 to 1.43;
      P<0.001) with CAD was stronger than that of LDL-C (OR, 1.10; 95% CI, 1.00 to
      1.21; P=0.047). The predictive value of LDL-TG for CAD was independent of LDL-C.
      "Sensitive" C-reactive protein (CRP), serum amyloid A, fibrinogen, interleukin 6,
      intercellular adhesion molecule-1 (ICAM-1), and vascular adhesion molecule-1
      (VCAM-1) increased in parallel to LDL-TG. CRP, ICAM-1, and VCAM-1 were inversely
      related to LDL-C. To examine whether LDL-TGs were associated with the
      distribution of LDL subfractions, we studied 114 individuals with impaired
      fasting glucose, impaired glucose tolerance, or type 2 diabetes mellitus. In
      subjects with high LDL-TG, LDLs were depleted of cholesteryl esters (CEs), and
      VLDLs, IDLs, and dense LDLs were significantly elevated. CONCLUSIONS: Alterations
      of LDL metabolism characterized by high LDL-TG are related to CAD, systemic low
      grade inflammation, and vascular damage. High LDL-TGs are indicative of CE
      depleted LDL, elevated IDL, and dense LDL. LDL-TG may better reflect the
      atherogenic potential of LDL than LDL-C.

PMID- 15505089
TI  - Modulation of doxorubicin-induced cardiac dysfunction in toll-like receptor-2
      knockout mice.
AB  - BACKGROUND: Toll-like receptors (TLRs) are members of the interleukin-1 receptor
      family and are involved in the responsiveness to pathogen-associated molecular
      patterns. Recent studies have demonstrated that TLRs are activated by endogenous
      signals, such as heat shock proteins and oxidative stress, which may contribute
      to congestive heart failure. Oxidative stress is one of the major factors in
      doxorubicin (Dox)-induced cardiac dysfunction. Thus, we hypothesized that TLRs
      contribute to the pathogenesis of Dox-induced cardiac dysfunction. METHODS AND
      RESULTS: Cardiac dysfunction was induced by a single injection of Dox (20 mg/kg
      IP) into wild-type (WT) mice and TLR-2-knockout (KO) mice. Five days after Dox
      injection, left ventricular dimension at end-diastole was smaller and fractional
      shortening was higher in KO mice compared with WT mice (P<0.01). Nuclear factor
      kappaB activation and production of proinflammatory cytokines after Dox were
      suppressed in KO mice compared with WT mice (P<0.01). The numbers of TUNEL
      positive nuclei and Dox-induced caspase-3 activation were less in KO mice than in
      WT mice (P<0.01). Survival rate was significantly higher in KO mice than in WT
      mice 10 days after Dox injection (46% vs 11%, P<0.05). CONCLUSIONS: These
      findings suggest that TLR-2 may play a role in the regulation of inflammatory and
      apoptotic mediators in the heart after Dox administration.

PMID- 15505090
TI  - Arterial neovascularization and inflammation in vulnerable patients: early and
      late signs of symptomatic atherosclerosis.
AB  - BACKGROUND: Atherosclerosis is complicated by cardiovascular events such as
      myocardial infarction, stroke, or peripheral arterial occlusive disease.
      Inflammation and pathological neovascularization are thought to precipitate
      plaque rupture or erosion, both causes of arterial thrombosis and cardiovascular
      events. We tested the hypothesis that arterial inflammation and angiogenic events
      are increased throughout the arterial tree in vulnerable patients, ie, in
      patients who suffered from cardiovascular events, compared with patients who
      never suffered from complications of atherosclerosis. METHODS AND RESULTS: In a
      postmortem study, we quantified the inflammatory infiltrate and microvascular
      network in the arterial wall of iliac, carotid, and renal arteries. Tissue
      microarray technology was adapted to investigate full-thickness arterial sectors.
      We compared 22 patients with symptomatic atherosclerosis with 27 patients who
      never had suffered from any cardiovascular event. The absolute intimal macrophage
      content was 2- to 4-fold higher in vulnerable patients at all 3 arterial sites
      analyzed (P<0.05). Patients with symptomatic atherosclerosis had a denser network
      of vasa vasorum than patients with asymptomatic disease (33+/-2 versus 25+/-2
      adventitial microvessels per 1 mm2; P=0.008). Hyperplasia of vasa vasorum was an
      early and macrophage infiltration was a late sign of symptomatic atherosclerosis.
      CONCLUSIONS: High intimal macrophage content and a hyperplastic network of vasa
      vasorum characterize vulnerable patients suffering from symptomatic
      atherosclerosis. These changes are uniformly present in different arterial beds
      and support the concept of symptomatic atherosclerosis as a panarterial disease.

PMID- 15505091
TI  - Noninducibility of atrial fibrillation as an end point of left atrial
      circumferential ablation for paroxysmal atrial fibrillation: a randomized study.
AB  - BACKGROUND: An anatomic approach of left atrial radiofrequency circumferential
      ablation (LACA) to encircle the pulmonary veins is often effective in eliminating
      paroxysmal atrial fibrillation (AF). However, no electrophysiological end points
      other than voltage abatement and/or conduction slowing or block across ablation
      lines have been used. It has been unclear whether noninducibility of AF is a
      clinically useful end point. METHODS AND RESULTS: In 100 patients with paroxysmal
      AF (mean age, 55+/-10 years), LACA to encircle the left- and right-sided
      pulmonary veins was performed during AF, with additional ablation lines in the
      posterior left atrium and mitral isthmus, with an 8-mm-tip catheter. After
      completion of this lesion set, sinus rhythm was present, and AF lasting >60
      seconds was not inducible in 40 patients (40%; group 1). The 60 patients in whom
      AF was still present or who still had inducible AF were randomly assigned to no
      further ablation (group 2; 30 patients) or to additional ablation lines along the
      left atrial septum, roof, and/or anterior wall where there were fractionated
      electrograms (group 3; 30 patients). In group 3, AF was rendered noninducible in
      27 of 30 patients (90%). At a 6-month follow-up, 67% of patients in group 2 were
      free of AF without drug therapy compared with 86% of patients in group 3.
      (P=0.05, log-rank test). Left atrial flutter occurred in 17% and 27% of patients
      in each group, respectively (P=0.3). CONCLUSIONS: After LACA in patients with
      paroxysmal AF, AF usually can be rendered noninducible by additional ablation at
      sites of fractionated electrograms. Noninducibility of AF attained by additional
      electrogram-guided left atrial ablation may be associated with a better midterm
      clinical outcome than when AF is still inducible after LACA alone.

PMID- 15505092
TI  - From mouse to whale: a universal scaling relation for the PR Interval of the
      electrocardiogram of mammals.
AB  - BACKGROUND: On the ECG, the PR interval measures the time taken by an electrical
      impulse generated in the sinoatrial node to propagate from atria to ventricles.
      From mouse to whale, the PR interval increases approximately 10(1), whereas body
      mass (BM) augments approximately 10(6). Scaling of many biological processes (eg,
      metabolic rate, life span, aortic diameter) is described by the allometric
      equation Y=Y(0) x BM(b), where Y is the biological process and b is the scaling
      exponent that is an integer multiple of 1/4. Hierarchical branching networks have
      been proposed to be the underlying mechanism for the 1/4 power allometric law.
      METHODS AND RESULTS: We first derived analytically the allometric equation for
      the PR interval. We assumed that the heart behaves as a set of "fractal-like"
      networks that tend to minimize propagation time across the conducting system
      while ensuring a hemodynamically optimal atrioventricular activation sequence.
      Our derivation yielded the relationship PR proportional, variant BM1/4. We
      subsequently obtained previously published values of PR interval, heart rate, and
      BM of 541 mammals representing 33 species. Double-logarithmic analysis
      demonstrates that PR interval increases as heart rate decreases, and both
      variables relate to BM following the 1/4 power law. Most important, the best fit
      for PR versus BM is described by the equation PR=53 x BM0.24. Hence, the
      empirically determined exponent (0.24) is close to 1/4, as predicted.
      CONCLUSIONS: We have demonstrated that the PR interval of mammals scales as the
      1/4 power of the BM, following the universal law for allometric scaling to ensure
      an optimal atrioventricular activation sequence.

PMID- 15505093
TI  - Vasoconstrictor reserve and sympathetic neural control of orthostasis.
AB  - BACKGROUND: We tested the hypothesis that individual variability in orthostatic
      tolerance is dependent on the degree of neural and vasomotor reserve available
      for vasoconstriction. METHODS AND RESULTS: Muscle sympathetic nerve activity
      (MSNA) and hemodynamics were measured in 12 healthy young volunteers during 60
      degrees head-up tilt (HUT), followed by a cold pressor test (CPT) in HUT.
      Orthostatic tolerance was determined by progressive lower-body negative pressure
      (LBNP) to presyncope. The same protocols were performed randomly in normovolemic
      and hypovolemic conditions. We found that mean arterial pressure increased and
      stroke volume decreased, whereas heart rate (HR), MSNA, and total peripheral
      resistance (TPR) increased during HUT (all P<0.01). Application of the CPT in HUT
      did not increase HR or decrease stroke volume further but elevated mean arterial
      pressure (P<0.01) and increased MSNA and TPR in some subjects. There was a
      positive correlation between the time to presyncope from -50 mm Hg LBNP
      (equivalent to 60 degrees HUT alone) and the changes in MSNA produced by the CPT
      under both conditions (r=0.442, P=0.039). Those who had greater increases in MSNA
      had greater increases in TPR during the CPT and longer time to presyncope (both
      P<0.05). One subject had dramatic increases in MSNA but small increases in TPR
      during the CPT, which indicates a disassociation between sympathetic activity and
      the increase in peripheral vascular resistance. CONCLUSIONS: These results
      support our hypothesis and suggest that vasoconstrictor capability is a
      contributor to orthostatic tolerance in humans. Vasoconstrictor reserve therefore
      may be one mechanism underlying individual variability in orthostatic
      intolerance.

PMID- 15505094
TI  - Hepatocyte growth factor suppresses vascular medial hyperplasia and matrix
      accumulation in advanced pulmonary hypertension of rats.
AB  - BACKGROUND: Pulmonary hypertension (PH) is a progressive disease characterized by
      raised pulmonary vascular resistance, thought to be curable only through lung
      transplantation. Pathophysiologically, proliferation of pulmonary artery smooth
      muscle cells triggers pulmonary arterial stenosis and/or regurgitation,
      especially in advanced PH. METHODS AND RESULTS: Using a rat model of advanced
      pulmonary vascular disease produced by injecting monocrotaline, we show that
      hepatocyte growth factor (HGF) targets pulmonary arterioles and blocks the
      progression of PH. In these rats, endogenous HGF production was dramatically
      downregulated during developing experimental PH, but c-Met/HGF receptor was
      abundant in the medial layers of pulmonary arterioles. HGF gene transfection 2
      weeks after the monocrotaline injection resulted in milder medial hyperplasia in
      lung arterioles and inhibited overgrowth of pulmonary artery smooth muscle cells.
      Notably, exogenous HGF reduced lung expression levels of endothelin-1 and
      transforming growth factor-beta, which are critically involved in PH-linked
      fibrogenic events. Overall, medial wall thickening of pulmonary arteries was
      almost completely prevented by HGF, and the total collagen deposition in the lung
      decreased; both effects contributed to the suppression of pulmonary artery
      hypertension. CONCLUSIONS: Our results suggest that the loss of endogenous HGF
      may be a feature of the pathogenesis of PH and that HGF supplementation may
      minimize pathological lung conditions, even advanced PH.

PMID- 15505096
TI  - Acute beta-blockade increases muscle sympathetic activity and modifies its
      frequency distribution.
AB  - BACKGROUND: The possible mechanisms by which beta-adrenergic antagonists may act
      on the neural regulation of the cardiovascular system are still elusive. Recent
      studies reported a marked increase of postganglionic muscle sympathetic nerve
      activity (MSNA) after acute beta-blockade associated with unchanged values of
      arterial blood pressure and baroreflex sensitivity. We tested the hypothesis that
      acute beta-blockade might also alter the oscillatory characteristics of MSNA,
      thus decreasing its effectiveness on peripheral vasoconstriction. METHODS AND
      RESULTS: In 11 healthy volunteers, ECG, MSNA, arterial pressure, and respiration
      were recorded before and after atenolol (0.05 mg/kg IV bolus) administration. The
      frequency distribution of RR interval, MSNA, systolic arterial pressure (SAP),
      and respiratory variability was assessed by spectrum and cross-spectrum analysis.
      Spontaneous baroreflex sensitivity (alpha-index) and plasma catecholamines (high
      performance liquid chromatography) were measured. Atenolol induced a significant
      increase in RR interval (14.3+/-1.6%) with no changes in systolic and diastolic
      arterial pressure. MSNA increased (42+/-13% from 18+/-2 bursts per minute). The
      low-frequency (LF) component of RR and MSNA variability decreased (-44+/-7% and 
      24+/-5%, respectively), whereas the high-frequency (HF) component increased
      (163+/-55% and 34+/-11%, respectively), expressed in normalized units. Spectral
      coherence, an index of oscillatory coupling, decreased between LF(RR) and
      LF(MSNA), whereas it increased between HF(MSNA) and HF(Resp). SAP variability,
      alpha-index, and plasma catecholamines remained unchanged. CONCLUSIONS: Atenolol
      induced a change in MSNA frequency distribution reflecting a stronger respiratory
      coupling. This shift toward high frequency, despite an increase in MSNA, may lead
      to a less efficient sympathetic vasomotor modulation.

PMID- 15505095
TI  - Effects of cardiac resynchronization on disease progression in patients with left
      ventricular systolic dysfunction, an indication for an implantable cardioverter
      defibrillator, and mildly symptomatic chronic heart failure.
AB  - BACKGROUND: The effects of cardiac resynchronization therapy (CRT) in patients
      with mildly symptomatic heart failure have not been fully elucidated. METHODS AND
      RESULTS: The Multicenter InSync ICD Randomized Clinical Evaluation II (MIRACLE
      ICD II) was a randomized, double-blind, parallel-controlled clinical trial of CRT
      in NYHA class II heart failure patients on optimal medical therapy with a left
      ventricular (LV) ejection fraction < or =35%, a QRS > or =130 ms, and a class I
      indication for an ICD. One hundred eighty-six patients were randomized: 101 to
      the control group (ICD activated, CRT off) and 85 to the CRT group (ICD
      activated, CRT on). End points included peak VO2, VE/CO2, NYHA class, quality of
      life, 6-minute walk distance, LV volumes and ejection fraction, and composite
      clinical response. Compared with the control group at 6 months, no significant
      improvement was noted in peak VO2, yet there were significant improvements in
      ventricular remodeling indexes, specifically LV diastolic and systolic volumes
      (P=0.04 and P=0.01, respectively), and LV ejection fraction (P=0.02). CRT
      patients showed statistically significant improvement in VE/CO2 (P=0.01), NYHA
      class (P=0.05), and clinical composite response (P=0.01). No significant
      differences were noted in 6-minute walk distance or quality of life scores.
      CONCLUSIONS: In patients with mild heart failure symptoms on optimal medical
      therapy with a wide QRS complex and an ICD indication, CRT did not alter exercise
      capacity but did result in significant improvement in cardiac structure and
      function and composite clinical response over 6 months.

PMID- 15505097
TI  - Excessive sarcoplasmic/endoplasmic reticulum Ca2+-ATPase expression causes
      increased sarcoplasmic reticulum Ca2+ uptake but decreases myocyte shortening.
AB  - BACKGROUND: Increasing sarcoplasmic/endoplasmic reticulum (SR) Ca2+-ATPase
      (SERCA) uptake activity is a promising therapeutic approach for heart failure. We
      investigated the effects of different levels of SERCA1a expression on
      contractility and Ca2+ cycling. We tested whether increased SERCA1a expression
      levels enhance myocyte contractility in a gene-dose-dependent manner. METHODS AND
      RESULTS: Rabbit isolated cardiomyocytes were transfected at different
      multiplicities of infection (MOIs) with adenoviruses encoding SERCA1a (or beta
      galactosidase as control). Myocyte relaxation half-time was decreased by 10%
      (P=0.052) at SERCA1a MOI 10 and by 28% at MOI 50 (P<0.05). Myocyte fractional
      shortening was increased by 12% at MOI 10 (P<0.05) but surprisingly decreased at
      MOI 50 (-22%, P<0.05) versus control. SR Ca2+ uptake (in permeabilized myocytes)
      demonstrated a gene-dose-dependent decrease in K(m) by 29% and 46% and an
      increase in Vmax by 37% and 72% at MOI 10 and MOI 50, respectively (all P<0.05
      versus control). Ca2+ transient amplitude was increased in Ad-SERCA1a-infected
      myocytes at MOI 10 (by 121%, P<0.05), but at MOI 50, the Ca2+ transient amplitude
      was not significantly changed. Caffeine-induced Ca2+ transients indicated
      significantly increased SR Ca2+ content in Ad-SERCA1a-infected cells, by 72% at
      MOI 10 and by 87% at MOI 50. Mathematical simulations demonstrate that the
      functional increase in SR Ca2+-ATPase uptake activity at MOI 50 (and increased
      cytosolic Ca2+ buffering) is sufficient to curtail the Ca2+ transient amplitude
      and explain the reduced contraction. CONCLUSIONS: Moderate SERCA1a gene transfer
      and expression improve contractility and Ca(2+) cycling. However, higher SERCA1a
      expression levels can impair myocyte shortening because of higher SERCA activity
      and Ca2+ buffering.

PMID- 15505098
TI  - Endothelium-dependent flow-mediated vasodilation of systemic arteries is impaired
      in patients with myocardial virus persistence.
AB  - BACKGROUND: Myocardial virus persistence is frequently observed in patients with
      cardiomyopathy. Endothelial dysfunction in patients with cardiomyopathy is
      associated with inflammatory immunoresponses in myocardial biopsies. The aim of
      this study was to investigate the impact of myocardial virus persistence on
      endothelial function. METHODS AND RESULTS: In 124 patients with suspected
      cardiomyopathy, myocardial biopsies were examined for virus persistence (by
      polymerase chain reaction) and inflammation (by immunohistology). Endothelial
      function of the radial artery was examined by high-resolution ultrasound.
      Diameter changes in response to reactive hyperemia (flow-mediated dilation [FMD])
      compared with glycerol trinitrate (GTN-MD) were measured. Mean age of the
      patients (55 men, 69 women) was 45+/-13 years; ejection fraction was 57+/-17%. In
      73 patients, adenovirus, enterovirus, parvovirus, or HHV6 virus (V) was detected;
      in 51, no virus was detected. FMD was significantly impaired in patients with
      myocardial virus persistence compared with control subjects (Co): FMD-V, 3.38+/
      2.67%; FMD-Co, 7.34+/-3.44 (P<0.001). In 86 patients, myocardial inflammation was
      confirmed (Inf). Of those, 57 had virus, and 29 did not. FMD was significantly
      impaired in patients with virus compared with controls: FMD-Inf-V, 3.24+/-2.66%;
      FMD-Inf-Co, 6.07+/-3.00 (P<0.001). In 38 patients, immunohistology of the
      myocardial biopsies was normal (Co); of those, 16 had virus, and 22 did not. FMD
      was impaired in patients with virus compared with control subjects: FMD-Co-V,
      3.88+/-2.72%; FMD-Co-Co, 9.00+/-3.32% (P<0.001). Endothelium-independent
      vasodilation (GTN-MD) was not significantly affected. CONCLUSIONS: Myocardial
      virus persistence is associated with endothelial dysfunction. Endothelial
      dysfunction in patients with myocardial virus persistence can occur independently
      of endothelial activation or myocardial inflammation but is more pronounced in
      patients with concurrent inflammation.

PMID- 15505099
TI  - Inhibitory G protein overexpression provides physiologically relevant heart rate
      control in persistent atrial fibrillation.
AB  - BACKGROUND: The need for new treatment strategies for cardiac arrhythmias has
      motivated our continuing development of gene therapeutic options. Previously, we
      reported a decreased heart rate in an acute model of atrial fibrillation after
      atrioventricular nodal gene transfer. Here, we expand those observations to
      persistent atrial fibrillation and severe heart failure. METHODS AND RESULTS:
      After 3 weeks of atrial fibrillation, domestic swine received atrioventricular
      nodal gene transfer with adenoviruses encoding beta-galactosidase (beta-gal),
      wild-type Galpha(i2) (wtGi), or constitutively active mutant (cGi). Heart rates
      in awake, alert animals were not altered by beta-gal or wtGi. cGi caused a
      sustained 15% to 25% decrease in heart rate. The wtGi effect became evident with
      sedation. A tachycardia-induced cardiomyopathy was present before gene transfer.
      In the beta-gal group, cardiomyopathy worsened over time. In the wtGi group, the
      condition improved slightly, and in the cGi group, ejection fraction was near
      normal at the end of the study. TUNEL staining results corroborated this finding.
      CONCLUSIONS: cGi overexpression in the porcine atrioventricular node causes
      physiologically relevant heart rate control in persistent atrial fibrillation.
      These data advance the development of gene therapy as a potential treatment for
      common cardiac arrhythmias.

PMID- 15505100
TI  - Subclinical coronary atherosclerosis in asymptomatic Filipino and white women.
AB  - BACKGROUND: Coronary heart disease (CHD) is the leading cause of morbidity and
      mortality in persons with type 2 diabetes mellitus (T2DM). Electron-beam computed
      tomography (EBCT) detects coronary artery calcium (CAC), a marker of
      atherosclerotic plaque. Few studies have described EBCT-defined CHD among ethnic
      minorities with elevated T2DM prevalence. The objective of this study was to
      compare EBCT-defined CAC in Filipino and white women without known cardiovascular
      disease. METHODS AND RESULTS: Subjects were participants aged 55 to 78 years in
      the Rancho Bernardo Study (n=196) and the University of California at San Diego's
      Filipino Women's Health Study (n=181). Glucose, blood pressure, lipids,
      anthropometric measurements, and lifestyle factors were measured from 1995 to
      1999. EBCT-defined CAC scores, visceral and subcutaneous fat, and statin use were
      assessed in 2001 to 2002. Compared with whites, Filipinas had a significantly
      higher prevalence of T2DM (32.6% versus 6.1%, P<0.001) and the metabolic syndrome
      (32.6% versus 13.8, P<0.001). Filipinas were younger (64.4 versus 66.7 years),
      had higher triglyceride levels (155 versus 135 mg/dL), had a higher ratio of
      total cholesterol to HDL cholesterol (4.3 versus 3.5), more frequently used
      statins (31% versus 19%), and had more visceral fat (69.4 versus 62.1 cm3) and
      lower HDL cholesterol levels (54 versus 66 mg/dL) than whites. Exercise
      frequency, body mass index, and waist girth did not differ by ethnicity.
      Nevertheless, extensive (CAC score > or =400; 9% versus 9%) and moderate (CAC
      score 150 to 399; 13% versus 11%) atherosclerotic plaque did not differ by
      ethnicity, even after adjustment for age, T2DM, hypertension, estrogen use,
      statin use, smoking, lipids, and visceral fat. CONCLUSIONS: Filipinas had no
      excess of subclinical atherosclerosis despite their significantly higher
      prevalence of T2DM, the metabolic syndrome, hypertension, and visceral adiposity.

PMID- 15505101
TI  - Gene expression profiling of inflamed human endothelial cells and influence of
      activated protein C.
AB  - BACKGROUND: During systemic inflammation, activation of vascular endothelium by
      proinflammatory cytokines leads to hypotension, microvascular thrombosis, and
      organ damage. Recent data suggest a link between coagulation and inflammation
      through the activated protein C (APC) pathway. We studied gene expression
      profiles in human coronary artery endothelial cells (HCAECs) exposed to
      proinflammatory stimuli and the influence of APC on expression of candidate genes
      regulated by these stimuli. METHODS AND RESULTS: HCAECs were stimulated with
      interleukin-1beta, interferon-gamma, and tumor necrosis factor-alpha. In gene
      expression profiling, 400 of 8400 genes were regulated >2-fold. Verification of
      selected candidate genes was achieved by measuring expression of mRNA species by
      real-time polymerase chain reaction, cytokine secretion by ELISA, and metabolites
      of tetrahydrobiopterin (BH4) biosynthesis by high-performance liquid
      chromatography. BH4 synthesis, interleukin-6, interleukin-8, monocyte chemotactic
      protein-1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) were
      downregulated by APC at the transcriptional and protein level. Endothelial nitric
      oxide synthase, endothelial adhesion molecule, and vascular cell adhesion
      molecule-1 were not affected by APC. Activities of transcription factors c-Fos,
      FosB, and c-Rel were inhibited by APC in inflamed HCAECs. CONCLUSIONS: Our study
      revealed a novel antiinflammatory mechanism of APC-dependent gene regulation in
      HCAECs since c-Fos-dependent induction of MCP-1 and ICAM-1 was suppressed. APC
      downregulates expression and activity of genes related to inflammation, most
      pronounced under intermediate or mild inflammatory conditions.

PMID- 15505102
TI  - Novel antiinflammatory vascular benefits of systemic and stent-based delivery of
      ethylisopropylamiloride.
AB  - BACKGROUND: Recently, we demonstrated that the amiloride derivative
      ethylisopropylamiloride (EIPA) limits vascular smooth muscle cell growth and
      migration. The purpose of the present experiments was to determine whether EIPA
      can also reduce the inflammatory component of atherogenesis and stent neointima
      formation. METHODS AND RESULTS: To determine the effect of EIPA on the early
      inflammatory stages of atherogenesis, apolipoprotein E null mice (apoE-/-) fed an
      atherogenic diet received a subcutaneous pump infusion of either EIPA (3 mg x kg(
      1)d(-1)) or the control vehicle for 4 weeks. The en face aortic area of
      atherosclerotic lesions and the subendothelial accumulation of macrophages were
      reduced by 46% and 38%, respectively, in EIPA-treated mice. Moreover, the number
      of vascular cell adhesion molecule-1 (VCAM-1) immunopositive lumenal endothelial
      cells was 59% less in the EIPA treatment group. In vitro, there was a
      concentration-dependent inhibition of lipopolysaccharide (LPS)-induced VCAM-1
      expression with a corresponding 37% reduction in U-937 cell adhesion to
      endothelial cells. EIPA also reduced LPS-stimulated nuclear factor-kappaB (NF
      kappaB) activation as reflected by a 66% reduction in NF-kappaB nuclear
      translocation. Finally, to test the effect of EIPA on the early inflammatory
      reaction to stent implantation, stents coated with jelly alone or jelly plus EIPA
      were implanted into rabbit iliac arteries. Four weeks later, the stent neointimal
      area, abundance of peristrut macrophages, and density of intimal smooth muscle
      cells were reduced by 38%, 47%, and 37%, respectively, for EIPA stents.
      CONCLUSIONS: EIPA downregulates endothelial cell activation of NF-kappaB and VCAM
      1 expression and attenuates the early inflammatory stages of atherogenesis and
      stent intimal formation.

PMID- 15505104
TI  - Stromal cell-derived factor-1 and CXCR4 interaction is critical for development
      of transplant arteriosclerosis.
AB  - BACKGROUND: Posttransplant chronic allograft deterioration associated with
      development of transplant arteriosclerosis (TA) remains an unresolved problem.
      Recent studies suggest that the smooth muscle cells (SMCs) constituting the
      neointima are derived from recipient hematopoietic stem cells (HSCs). However,
      the underlying mechanisms of the process are not yet fully elucidated. METHODS
      AND RESULTS: We examined the genes expressed in allografts at different stages of
      TA development using a mice aortic transplantation model. Genes were analyzed by
      a differential mRNA display technique. We show that stromal cell-derived factor
      1alpha (SDF-1alpha) is a critical molecular target for the treatment of TA.
      During the course of TA, intragraft SDF-1alpha expression was upregulated with
      time, and the circulating HSCs expressing its counterreceptor CXCR4 increased in
      the recipients receiving allografts. CXCR4-positive HSCs, derived from transplant
      recipients, migrated into allografts via microvessels in the adventitia and then
      toward the luminal side. The HSCs differentiated into SMC-like cells,
      contributing to the in situ formation of the neointima. In support of a
      functional role for these molecules, in vivo neutralization of SDF-1alpha
      inhibited HSC mobilization and significantly attenuated neointimal formation.
      CONCLUSIONS: Interaction between SDF-1alpha and CXCR4 plays a key role in TA
      development. Blockade of SDF-1alpha may become a new therapeutic modality for TA.

PMID- 15505103
TI  - Deletion of p66shc gene protects against age-related endothelial dysfunction.
AB  - BACKGROUND: Enhanced production of reactive oxygen species (ROS) has been
      recognized as the major determinant of age-related endothelial dysfunction. The
      p66shc protein controls cellular responses to oxidative stress. Mice lacking
      p66shc (p66shc-/-) have increased resistance to ROS and a 30% prolonged life
      span. The present study investigates age-dependent changes of endothelial
      function in this model. METHODS AND RESULTS: Aortic rings from young and old
      p66shc-/- or wild-type (WT) mice were suspended for isometric tension recording.
      Nitric oxide (NO) release was measured by a porphyrinic microsensor. Expression
      of endothelial NO synthase (eNOS), inducible NOS (iNOS), superoxide dismutase,
      and nitrotyrosine-containing proteins was assessed by Western blotting.
      Nitrotyrosine residues were also identified by immunohistochemistry. Superoxide
      (O2-) production was determined by coelenterazine-enhanced chemiluminescence.
      Endothelium-dependent relaxation in response to acetylcholine was age-dependently
      impaired in WT mice but not in p66shc-/- mice. Accordingly, an age-related
      decline of NO release was found in WT but not in p66shc-/- mice. The expression
      of eNOS and manganese superoxide dismutase was not affected by aging either in WT
      or in p66shc-/- mice, whereas iNOS was upregulated only in old WT mice. It is
      interesting that old WT mice displayed a significant increase of O2- production
      as well as of nitrotyrosine expression compared with young animals. Such age
      dependent changes were not found in p66shc-/- mice. CONCLUSIONS: We report that
      inactivation of the p66shc gene protects against age-dependent, ROS-mediated
      endothelial dysfunction. These findings suggest that the p66shc is part of a
      signal transduction pathway also relevant to endothelial integrity and may
      represent a novel target to prevent vascular aging.

PMID- 15505105
TI  - Anti-glycoprotein VI treatment severely compromises hemostasis in mice with
      reduced alpha2beta1 levels or concomitant aspirin therapy.
AB  - BACKGROUND: Platelet inhibition is a major strategy to prevent arterial
      thrombosis, but it is frequently associated with increased bleeding because of
      impaired primary hemostasis. The activating platelet collagen receptor,
      glycoprotein VI (GP VI), may serve as a powerful antithrombotic target because
      its inhibition or absence results in profound protection against arterial
      thrombosis but no major bleeding in mice. METHODS AND RESULTS: Mice lacking (-/-)
      or expressing half-levels (+/-) of the other major platelet collagen receptor,
      integrin alpha2beta1, were injected with the anti-GP VI antibody JAQ1 and
      analyzed on day 5. Anti-GP VI treatment resulted in a marked hemostatic defect in
      alpha2-/- or alpha2+/- mice, as shown by dramatically prolonged tail bleeding
      times. Platelet adhesion to collagen was studied in an ex vivo whole-blood
      perfusion system under high shear conditions. Weak integrin activation by
      thromboxane A2 (TxA2) receptor stimulation restored defective adhesion of anti-GP
      VI-treated wild-type but not alpha2-/- or alpha2+/- platelets to collagen. This
      process required the simultaneous activation of the G(q) and G13 signaling
      pathways, as demonstrated by use of the respective knockout strains. Conversely,
      inhibition of TxA2 production by aspirin severely compromised hemostasis in anti
      GP VI-treated or GP VI/Fc receptor gamma-chain-deficient but not control mice.
      CONCLUSIONS: Anti-GP VI therapy may result in defective hemostasis in patients
      with reduced alpha2beta1 levels or concomitant aspirin therapy. These
      observations may have important implications for a potential use of anti-GP VI
      based therapeutics in the prevention of cardiovascular disease.

PMID- 15505106
TI  - Novel model of constrictive pericarditis associated with autoimmune heart disease
      in interferon-gamma-knockout mice.
AB  - BACKGROUND: Constrictive pericarditis represents a serious hemodynamic syndrome
      that may lead to heart failure. Studies of its pathophysiological mechanisms have
      been impeded by the lack of an animal model. METHODS AND RESULTS: Cardiac myosin
      induced experimental autoimmune myocarditis in interferon (IFN)-gamma-knockout
      (KO) mice results in increased cardiac inflammation and development of severe
      grossly detectable pericarditis. Using in vivo pressure-volume studies, we found
      that the acute phase of experimental autoimmune myocarditis in IFN-gamma-KO mice
      was characterized by reduced left ventricular (LV) volumes compared with wild
      type mice. The KO mice exhibited a classic restrictive/constrictive phenotype
      with decreased cardiac output, increased chamber stiffness, preserved ejection
      fraction, and impaired diastolic filling, characterized by reduced deceleration
      time and pressure tracings showing the square root sign similar to that observed
      in clinical cases of constrictive pericarditis. This phenotype was not associated
      with the severity of myocarditis but correlated with the presence of grossly
      detectable adhesive pericarditis present only in the KO group and characterized
      by increased pericardial inflammation and fibrosis. Comparison of IFN-gamma-KO
      and wild-type mice matched for the severity of myocardial disease further
      confirmed that pericarditis, and not myocarditis, was responsible for smaller LV
      volumes, reduced cardiac output, increased cardiac stiffness, and increased peak
      filling rate adjusted for end-diastolic volumes in KO mice. CONCLUSIONS:
      Autoimmune heart disease in IFN-gamma-KO mice results in increased pericardial
      inflammation and fibrosis, leading to constrictive phenotype during the acute
      phase of disease. It represents a novel animal model of constrictive
      pericarditis.

PMID- 15505107
TI  - Images in cardiovascular medicine. Right atrial primary cardiac lymphoma
      presenting with stroke.

PMID- 15505108
TI  - Are anti-oxidized low-density lipoprotein antibodies pathogenic or protective?

PMID- 15505109
TI  - Cellular basis for therapeutic choices in heart failure.

PMID- 15505110
TI  - 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, timeframes, 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- 15505111
TI  - Diagnosis, treatment, and long-term management of Kawasaki disease: a statement
      for health professionals from the Committee on Rheumatic Fever, Endocarditis and
      Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart
      Association.
AB  - BACKGROUND: Kawasaki disease is an acute self-limited vasculitis of childhood
      that is characterized by fever, bilateral nonexudative conjunctivitis, erythema
      of the lips and oral mucosa, changes in the extremities, rash, and cervical
      lymphadenopathy. Coronary artery aneurysms or ectasia develop in approximately
      15% to 25% of untreated children and may lead to ischemic heart disease or sudden
      death. METHODS AND RESULTS: A multidisciplinary committee of experts was convened
      to revise the American Heart Association recommendations for diagnosis,
      treatment, and long-term management of Kawasaki disease. The writing group
      proposes a new algorithm to aid clinicians in deciding which children with fever
      for > or =5 days and < or =4 classic criteria should undergo echocardiography,
      receive intravenous gamma globulin (IVIG) treatment, or both for Kawasaki
      disease. The writing group reviews the available data regarding the initial
      treatment for children with acute Kawasaki disease, as well for those who have
      persistent or recrudescent fever despite initial therapy with IVIG, including
      IVIG retreatment and treatment with corticosteroids, tumor necrosis factor-alpha
      antagonists, and abciximab. Long-term management of patients with Kawasaki
      disease is tailored to the degree of coronary involvement; recommendations
      regarding antiplatelet and anticoagulant therapy, physical activity, follow-up
      assessment, and the appropriate diagnostic procedures to evaluate cardiac disease
      are classified according to risk strata. CONCLUSIONS: Recommendations for the
      initial evaluation, treatment in the acute phase, and long-term management of
      patients with Kawasaki disease are intended to assist physicians in understanding
      the range of acceptable approaches for caring for patients with Kawasaki disease.
      The ultimate decisions for case management must be made by physicians in light of
      the particular conditions presented by individual patients.

PMID- 15505112
TI  - Endothelin-1 gene and progression of blood pressure and left ventricular mass:
      longitudinal findings in youth.
AB  - Endothelin-1 (ET-1) is a powerful vasconstrictor peptide implicated in
      development of essential hypertension and left ventricular hypertrophy. To
      evaluate the impact of genetic variability of the ET-1 gene on progression of
      blood pressure (BP) and left ventricular mass (LVM), we conducted individual
      growth curve modeling for 537 European American and black youths with 12
      assessments during a 15-year period. Four common single-nucleotide polymorphisms
      (SNPs) including T-1370G, +138/ex1 del/ins, T-37/in2C, and Lys198Asn were
      included in this study. Single SNP analyses showed that individuals with the
      +138/ex1 ins allele had a borderline significant lower systolic BP (SBP;
      P=0.072). Furthermore, the -37/in2C allele showed an SBP-lowering effect in
      males, accounting for 1.6% between-subject variation of SBP (P=0.016). Haplotype
      analyses in males confirmed the BP-lowering effect of the -37/in2C allele. SBP in
      individuals homozygous for the del (+138/ex1) -C (-37/in2) haplotype was 3.3 mm
      Hg lower than those homozygous for the del (+138/ex1) -T (-37/in2) haplotype
      (P=0.038). For LVM, we observed a significant gene-environment interaction. LVM
      levels were 20 g higher in carriers versus noncarriers of the -1370G allele in
      the low socioeconomic status (SES) group only (P=0.004). In summary, our results
      uncover a sex-specific protective effect of variation in the ET-1 gene on the
      progression of hypertension risk, and a SES-specific effect on risk of developing
      left ventricular hypertrophy in multiethnic youth.

PMID- 15505113
TI  - Vascular response to angiotensin II predicts long-term prognosis in patients
      undergoing coronary artery bypass grafting.
AB  - Persistent activation of the renin-angiotensin system leads to downregulation of
      the angiotensin type-1 receptor, and consequently, to a decreased response to
      exogenous angiotensin II. In the present study, we investigated the association
      of angiotensin II responsiveness to clinical outcome after coronary artery bypass
      grafting (CABG). We studied the responsiveness to exogenous angiotensin II in
      human thoracic artery preparations of 114 CABG patients. Mean duration of follow
      up was 7.3+/-0.1 years, during which 21 patients experienced a cardiovascular
      event. A diminished response to angiotensin II remained in multivariate Cox
      regression analysis, after adjustment for sex, age, blood pressure, and number of
      diseased coronary arteries, the strongest predictor for cardiovascular events
      (relative risk, 3.37 [95% confidence interval, 1.20 to 9.51]; P=0.022).
      Furthermore, diminished response to angiotensin II was associated with an
      increased mean arterial pressure (102.85+/-1.38 versus 97.40+/-1.37; P=0.003) and
      a nonsignificant increase in angiotensin-converting enzyme activity, suggestive
      for a persistently activated renin-angiotensin system. In conclusion, these
      results suggest that in patients undergoing CABG, a diminished vascular
      responsiveness of the thoracic artery to exogenous angiotensin II is related to
      an increased risk of future cardiovascular events.

PMID- 15505114
TI  - cGMP-dependent protein kinase mediates NO- but not acetylcholine-induced
      dilations in resistance vessels in vivo.
AB  - cGMP and cGMP-dependent protein kinase type I (cGKI) mediate the dilation of
      large vessels in response to NO and acetylcholine (ACh). However, the
      physiological significance of the NO/cGMP/cGKI pathway in resistance vessels is
      controversial. Here, we analyzed NO- and ACh-induced dilations of arterioles in
      cGKI-deficient (cGKI-/-) or endothelial NO synthase-deficient (eNOS-/-) mice.
      Mean arterial pressure was similar in cGKI-/- and wild-type mice (105 mm Hg).
      Pressure drops in response to intracarotid bolus application of the NO donor
      sodium nitroprusside (SNP) were almost abolished in cGKI-/- mice, whereas ACh
      induced pressure decreases remained intact in cGKI-/- and eNOS-/- mice. The
      direct observation of arterioles in the cremaster muscle by intravital microscopy
      showed impaired SNP-induced dilations in cGKI-/- mice (by 80%) and normal ACh
      induced dilations in cGKI-/- and eNOS-/- mice. ACh-induced dilations in eNOS-/-
      mice were attenuated by iberiotoxin (by 50%), indicating that they were mediated
      in part by Ca2+-activated K+ channels, but not by inhibitors of cyclooxygenase or
      p450-monooxygenases. We conclude that cGMP and cGKI are the major effectors of NO
      to induce acute dilations of murine resistance vessels. However, the NO/cGMP/cGKI
      pathway is not essential for ACh-induced dilation of arterioles and for basal
      blood pressure regulation in mice.

PMID- 15505115
TI  - Potassium chloride supplementation diminishes platelet reactivity in humans.
AB  - The prevalence of occlusive stroke is inversely correlated with potassium intake.
      We explored the hypothesis that a high potassium intake attenuates platelet
      reactivity, as expressed in ADP-evoked platelet aggregation. We studied healthy
      men (n=31) and women (n=42), blacks (n=33) and whites (n=40). In this cohort, we
      supplemented the habitual intake of 17 men and 21 women with 60 mmol KCl/70 kg
      body weight per day for 3 days and maintained 14 men and 21 women on their
      habitual intake. We then compared the change in ADP concentration causing 50% of
      the maximal initial rate (EC50) of platelet aggregation in the potassium
      supplemented versus control groups. Potassium supplementation attenuated platelet
      reactivity, expressed by an increase in EC50 of platelet aggregation (P=0.0005),
      which was primarily attributable to an increase in EC50 in whites (P=0.0004).
      Urinary potassium excretion was significantly lower in blacks than in whites
      under basal conditions and after potassium supplementation. We conclude that
      potassium supplementation diminishes platelet reactivity, a phenomenon that
      provides a link between platelet biology and occlusive stroke.

PMID- 15505116
TI  - Effects of NOS3 Glu298Asp polymorphism on hemodynamic reactivity to stress:
      influences of ethnicity and obesity.
AB  - Studies on the associations between the nitric oxide synthase gene (NOS3)
      Glu298Asp polymorphism and hypertension status or blood pressure (BP) levels have
      had inconsistent results. Potential moderating influences of ethnicity, sex, and
      obesity on the effects of the NOS3 polymorphism have not been examined. We
      evaluated the influence of these factors on associations between the NOS3
      polymorphism, nitric oxide metabolites (NOx), and hemodynamics at rest and during
      stress. Subjects were 235 African American (AA) and 262 European American (EA)
      young adults (18.5+/-2.6 years). Hemodynamic measurements and blood samples for
      NOx assays were taken before and after a competitive video game challenge.
      Glu298Asp polymorphism was detected by polymerase chain reaction-restriction
      enzyme digestion assay. A regression model was built using genotypes, ethnicity,
      sex, and obesity (body mass index >85th percentile) and their interactions
      controlling for age; 20.1% of AAs and 49.8% of EAs were carriers of the Asp
      allele. AAs, regardless of obesity status, exhibited high diastolic blood
      pressure (DBP) reactivity unless they were nonobese and noncarriers of the Asp
      allele. EAs exhibited lower DBP reactivity unless they were obese Asp allele
      carriers. AA nonobese carriers exhibited the greatest total peripheral resistance
      reactivity. Obese Asp allele carriers exhibited the greatest increases in cardiac
      output and the greatest decrease in NOx to the stressor. Results indicate the
      importance of examining impact of BP control-related genetic polymorphisms within
      the context of moderating factors such as adiposity and ethnicity.

PMID- 15505117
TI  - Impairment of PI3-K/Akt pathway underlies attenuated endothelial function in
      aorta of type 2 diabetic mouse model.
AB  - The phosphatidylinositol 3-kinase (PI3-K) pathway, which activates
      serine/threonine protein kinase Akt, enhances endothelial nitric oxide synthase
      (eNOS) phosphorylation and nitric oxide (NO) production. We investigated the
      involvement of the PI3-K/Akt pathway in the relaxation responses to acetylcholine
      (ACh) and clonidine in a new type 2 diabetic model (streptozotocin plus
      nicotinamide-induced diabetic mice). Plasma glucose and insulin levels were
      significantly elevated in our model, and intravenous glucose tolerance tests
      revealed clear abnormalities in glucose tolerance and insulin responsiveness.
      Although in our model the ACh-induced relaxation and NOx- (NO2-+NO3-)/cGMP
      production were unchanged, the clonidine-induced and insulin-induced relaxations
      and NOx-/cGMP production were all greatly attenuated. In control mice, the
      clonidine-induced and insulin-induced relaxations were each abolished by LY294002
      and by Wortmannin (inhibitors of PI3-K), and also by Akt-inhibitor treatment. The
      ACh-induced relaxation was unaffected by such treatments in either group of mice.
      The expression level of total Akt protein was significantly decreased in the
      diabetic mice aorta, but those for the p85 and p110gamma subunits of PI3-K were
      not. The clonidine-induced Ser-473 phosphorylation of Akt through PI3-K was
      significantly decreased in our model; however, that induced by ACh was not. These
      results suggest that relaxation responses and NO production mediated via the PI3
      K/Akt pathway are decreased in this type 2 diabetic model. This may be a major
      cause of endothelial dysfunction (and the resulting hypertension) in type 2
      diabetes.

PMID- 15505118
TI  - Fetal and early life determinants of hypertension in adults: implications for
      study.

PMID- 15505119
TI  - Management of hypertension in the very elderly patient.
AB  - This Hypertension Grand Rounds discusses pharmacological treatment of
      hypertension in individuals who have survived 9 decades on earth. This rapidly
      growing group of relatively active and healthy elderly people is at high risk for
      hypertension, its treatment, and its adverse consequences, including stroke and
      heart failure. In this age group, the most common abnormality is elevated
      systolic blood pressure, which is much more predictive of stroke and heart
      disease death after 53 years of age. With the possible exception of the
      Antihypertensive and Lipid Lowering to prevent Heart Attack Trial (ALLHAT),
      recent clinical trials have emphasized the overriding importance of lowering
      blood pressure rather than the specific agent chosen to begin therapy. In 1999, a
      metaanalysis of 7 clinical trials that enrolled 1670 subjects >80 years of age
      indicated that active antihypertensive drug therapy significantly reduced stroke
      by 34% and heart failure by 39% but was associated with a nonsignificant 6%
      increase in mortality. The HYpertension in the Very Elderly Trial (HYVET) will
      enroll 2100 patients >80 years of age and will compare 2 groups randomized to
      indapamide+/-perindopril versus placebo+/-placebo for incident stroke during 5
      years of follow-up. This study should answer lingering questions about whether
      active antihypertensive therapy is associated with a major and significant
      reduction in cardiovascular morbidity and mortality in this age group as it
      clearly does in younger hypertensives. Its choice of a diuretic as initial
      therapy is consistent with other trials, but chlorthalidone is the drug with the
      most compelling evidence in large US trials that included very elderly patients.

PMID- 15505120
TI  - Today's agenda: we must focus on achieving favorable levels of all risk factors
      simultaneously.

PMID- 15505121
TI  - Postprandial glucose regulation and diabetic complications.
AB  - Atherosclerotic disease accounts for much of the increased mortality and
      morbidity associated with type 2 diabetes. Epidemiological studies support the
      potential of improved glycemic control to reduce cardiovascular complications. An
      association between glycosylated hemoglobin (HbA(1c)) level and the risk for
      cardiovascular complications has frequently been reported. Most epidemiological
      data implicate postprandial hyperglycemia in the development of cardiovascular
      disease, whereas the link between fasting glycemia and diabetic complications is
      inconclusive. Moreover, in many studies, postprandial glycemia is a better
      predictor of cardiovascular risk than HbA(1c) level. Postprandial glucose may
      have a direct toxic effect on the vascular endothelium, mediated by oxidative
      stress that is independent of other cardiovascular risk factors such as
      hyperlipidemia. Postprandial hyperglycemia also may exert its effects through its
      substantial contribution to total glycemic exposure. The present review examines
      the hypothesis that controlling postprandial glucose level is an important
      strategy in the prevention of cardiovascular complications associated with
      diabetes.

PMID- 15505122
TI  - A meta-analysis comparing the effect of thiazolidinediones on cardiovascular risk
      factors.
AB  - BACKGROUND: In patients with type 2 diabetes mellitus, all therapeutic options
      should be evaluated for their effect on cardiovascular risk factors, in addition
      to glycemic control. We conducted a meta-analysis of randomized controlled trials
      of pioglitazone hydrochloride and rosiglitazone maleate in patients with type 2
      diabetes to evaluate their effect on glycemic control, lipids, blood pressure,
      and weight. METHODS: Randomized controlled trials of patients with type 2
      diabetes that compared pioglitazone or rosiglitazone with placebo for 12 weeks
      were included. Primary analysis was to compare thiazolidinediones with placebo.
      Secondary analysis was to identify whether treatment with pioglitazone differed
      from rosiglitazone in any outcomes. We calculated weighted mean differences and
      95% confidence intervals. RESULTS: Twenty-three randomized controlled trials were
      identified. Both thiazolidinediones demonstrated similar hemoglobin A(1c) level
      decreases of 1.0% to 1.5% and similar increases in body weight of approximately
      3.0 kg. Pioglitazone significantly lowered triglyceride level (-40 mg/dL [-0.45
      mmol/L]; 95% confidence interval [CI], -53 to -26 mg/dL [-0.60 to -0.29 mmol/L]),
      increased high-density lipoprotein cholesterol (HDL-C) level (+4.6 mg/dL [+0.12
      mmol/L]; 95% CI, 3.6 to 5.5 mg/dL [0.09 to 0.14 mmol/L]), and showed neutral
      effect on low-density lipoprotein cholesterol (LDL-C) and total cholesterol
      levels. Rosiglitazone significantly increased HDL-C level (+2.7 mg/dL [+0.07
      mmol/L]; 95% CI, 2.0 to 3.4 mg/dL [0.05 to 0.09 mmol/L]), but increased LDL-C
      level (+15 mg/dL [+0.39 mmol/L]; 95% CI, 13 to 17 mg/dL [0.34 to 0.44 mmol/L]),
      total cholesterol level (+21 mg/dL [+0.54 mmol/L]; 95% CI, 18 to 25 mg/dL [0.47
      to 0.65 mmol/L]), and demonstrated neutral effect on triglyceride level (-1.1
      mg/dL [-0.12 mmol/L]; 95% CI, -14 to 12 mg/dL [-0.16 to 0.14 mmol/L]). No data
      were available on pioglitazone and blood pressure. Rosiglitazone had a neutral
      effect on systolic (-0.7 mm Hg; 95% CI, -2.6 to 1.1 mm Hg) and diastolic (-0.8 mm
      Hg; 95% CI, -1.8 to 0.3) blood pressure. CONCLUSIONS: Thiazolidinediones have
      similar effects on glycemic control and body weight. Pioglitazone produced a more
      favorable lipid profile. Head-to-head comparative trials as well as longer-term
      cardiovascular outcome studies are needed to determine whether there are
      differences in efficacy between the 2 thiazolidinediones.

PMID- 15505123
TI  - Comparative benefits of clopidogrel and aspirin in high-risk patient populations:
      lessons from the CAPRIE and CURE studies.
AB  - Clopidogrel has been evaluated in clinical trials that included cardiovascular
      patients with different risk levels for a cardiovascular event. We reviewed the
      results of the Clopidogrel vs Aspirin in Patients at Risk of Ischemic Events
      (CAPRIE) and Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE)
      trials, with special emphasis on comparing the outcomes in high-risk patients
      with those of the total populations in the trials. The results in the high-risk
      subgroups and total populations were compared by recording total event rates,
      absolute risk reduction, relative risk reduction, and number needed to treat. In
      the CAPRIE trial, the efficacy of clopidogrel was compared with acetylsalicylic
      acid (ASA) in the following subgroups: total population, previous coronary bypass
      surgery, history of more than 1 ischemic event, multiple vascular beds
      involvement, diabetes, and hypercholesterolemia. In the CURE trial, the
      combination of clopidogrel and ASA was compared with ASA alone. The results in
      the CURE study were compared in patients who did and did not have a coronary
      intervention procedure, in patients with different levels of risk based on the
      Thrombolysis in Myocardial Infarction score and in patients with and without a
      history of a revascularization procedure. High-risk subgroups of patients
      participating in the CAPRIE and CURE studies were more responsive to the
      beneficial effects of clopidogrel compared with the study population as a whole.
      High-risk groups in the CAPRIE and CURE studies would be expected to derive
      enhanced benefit from treatment with clopidogrel over that achieved by ASA.

PMID- 15505124
TI  - Prevalence of heart disease and stroke risk factors in persons with
      prehypertension in the United States, 1999-2000.
AB  - BACKGROUND: Recent guidelines classify persons with above-optimal blood pressure
      (BP) but not clinical hypertension as having prehypertension. METHODS: Data were
      analyzed for 3488 persons aged 20 years and older with BP measured in the 1999
      2000 National Health and Nutrition Examination Survey. The prevalence of risk
      factors-above-normal (> or =200 mg/dL [> or =5.17 mmol/L]) and high (> or =240
      mg/dL [> or =6.21 mmol/L]) total cholesterol levels, diabetes mellitus, current
      smoker, and overweight or obesity-and the number of risk factors present were
      compared among BP groups (normotension, prehypertension, and hypertension).
      Multivariable logistic regression included age, sex, and race/ethnicity as
      covariates. RESULTS: Overall, 39% of persons were normotensive,31% were
      prehypertensive, and 29% were hypertensive. The age-adjusted prevalence of
      prehypertension was greater in men (39.0%) than in women (23.1%). African
      Americans aged 20 to 39 years had a higher prevalence of prehypertension (37.4%)
      than whites (32.2%) and Mexican Americans (30.9%), but their prevalence was lower
      at older ages because of a higher prevalence of hypertension. The probabilities
      of above-normal cholesterol levels, overweight/obesity, and diabetes mellitus
      were greater for persons with prehypertension vs normotension, whereas the
      probability of currently smoking was lower. Persons with prehypertension were
      1.65 times more likely to have at least 1 other adverse risk factor than were
      those with normotension (P<.001). Among participants with prehypertension, there
      were no significant race/ethnic or sex differences in the likelihood of having at
      least 1 other risk factor. CONCLUSIONS: The greater prevalence of risk factors in
      persons with prehypertension vs normotension suggests the continued need for
      early clinical detection and intervention of prehypertension and comprehensive
      preventive and public health efforts.

PMID- 15505125
TI  - Effects of prehypertension on admissions and deaths: a simulation.
AB  - BACKGROUND: The Joint National Committee on Prevention, Detection, Evaluation,
      and Treatment of High Blood Pressure recently released new clinical practice
      guidelines that target systolic blood pressure and identify persons with
      "prehypertension" (systolic blood pressure, 120-139 mm Hg), previously considered
      normal, as being at elevated risk and in need of intervention. METHODS: We used a
      simulation model, fitted to longitudinal data from the first NHANES (National
      Health and Nutrition Examination Survey) Epidemiologic Followup Study, to
      estimate the effects of prehypertension and residual hypertension (systolic blood
      pressure, > or =140 mm Hg). The term residual hypertension recognizes that many
      people with hypertension have lowered their pressures through treatment, but not
      to less than 140 mm Hg. We applied the model to a representative sample of US
      adults aged 25 to 74 years from NHANES III. RESULTS: Except for women aged 25 to
      44 years, more than a third of each age group in NHANES III had prehypertension.
      Approximately two thirds of persons aged 45 to 64 years and 80% of persons aged
      65 to 74 years had prehypertension or residual hypertension. Together,
      prehypertension and residual hypertension accounted for 4.7% of hospital
      admissions per 10 000 adults aged 25 to 74 years, 9.7% of nursing home
      admissions, and 13.7% of deaths. Prehypertension alone accounted for 3.4% of
      hospitalizations, 6.5% of nursing home stays, and 9.1% of deaths. Numbers of
      events attributable to prehypertension are greatest for men aged 45 to 64 years
      and persons aged 65 to 74 years. CONCLUSIONS: Our results confirm the substantial
      public health consequences of prehypertension. If prehypertension were
      eliminated, hospitalizations, nursing home admissions, and premature deaths could
      decline substantially.

PMID- 15505126
TI  - The prevalence of prehypertension and hypertension among US adults according to
      the new joint national committee guidelines: new challenges of the old problem.
AB  - BACKGROUND: The recently released Seventh Report of the Joint National Committee
      (JNC) on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure
      provides a new classification of blood pressure levels. Little is known about the
      current situation of elevated blood pressure in the United States, according to
      the new guidelines. METHODS: Cross-sectional analysis of national representative
      data collected from 4805 adults 18 years and older surveyed in the 1999-2000
      National Health and Nutrition Examination Survey. We examined the prevalence of
      prehypertension and hypertension according to the new JNC guidelines, people's
      awareness and management of hypertension, and the differences across
      sociodemographic and body weight groups. RESULTS: Elevated blood pressure is a
      serious problem in the United States. Approximately 60% of American adults have
      prehypertension or hypertension, and some population groups, such as African
      Americans, older people, low-socioeconomic-status groups, and overweight groups,
      are disproportionately affected. The prevalence of hypertension has increased by
      approximately 10 percentage points during the past decade. The awareness and
      appropriate management of hypertension among hypertensive patients remain low:
      31% were not aware of their disease, only two thirds (66%) were told by health
      professionals to adopt lifestyle modifications or take drugs to control
      hypertension, and only 31% controlled their hypertension. CONCLUSIONS: With 60%
      of the population affected, the United States is facing a serious challenge in
      the prevention and management of prehypertension and hypertension. People's
      awareness and control of hypertension remain poor. This study highlights the
      seriousness of the problem and the importance of promoting lifestyle
      modifications.

PMID- 15505127
TI  - Health services use and health care costs of obese and nonobese individuals.
AB  - BACKGROUND: Obesity has clinical and economic consequences. Few studies have
      compared health care resource utilization between age- and sex-matched obese and
      nonobese persons. METHODS: We conducted a retrospective study in obese and
      nonobese individuals matched by age, sex, medical clinic, and selected
      exclusionary diagnoses. Data collected included hospitalizations, outpatient
      visits, professional claims, and prescriptions over 1 year. Costs were assigned
      to medical resources based on market prices using publicly available costs.
      Comorbid conditions were determined using a chronic disease score (CDS) index.
      Groups were compared on types and costs of resources consumed. Regression models
      were used to examine the effect of body mass index (BMI) on costs while
      controlling for age and chronic diseases. RESULTS: A total of 539 obese and 1225
      nonobese persons were examined. Obese patients had more hospitalizations
      (P<.001), prescription drugs (P<.001), professional claims (P<.001), and
      outpatient visits (P = .005). Obese patients used more cardiovascular, intranasal
      allergic rhinitis, asthma, ulcer, diabetes, thyroid, and analgesic drugs. Total
      costs between groups were different (median of $585.44 for obese and $333.24 for
      nonobese patients; P<.001). Cost differences were primarily due to medications
      (P<.001). Predictors of total costs were age, sex, BMI, and CDS. For each unit
      BMI increase, costs increased 2.3% (P<.001). For each CDS unit increase, costs
      increased 52.9% (P<.001). CONCLUSION: Over 1 year, health care costs for obese
      persons are higher than for nonobese persons, primarily because of prescription
      drugs.

PMID- 15505129
TI  - Is nondiabetic hyperglycemia a risk factor for cardiovascular disease? A meta
      analysis of prospective studies.
AB  - BACKGROUND: Although hyperglycemia increases the risk of cardiovascular disease
      (CVD) in diabetic patients, the risk associated with blood glucose levels in the
      nondiabetic range remains unsettled. METHODS: We identified 38 reports in which
      CVD incidence or mortality was an end point, blood glucose levels were measured
      prospectively, and the relative risk (RR) and information necessary to calculate
      the variance were reported comparing groups of nondiabetic people. These reports
      were prospective studies, published in English-language journals. First author,
      publication year, participant age and sex, study duration, CVD end points,
      glucose assessment methods, control for confounding, range of blood glucose
      levels, RR, and confidence intervals (CIs) or P values were extracted. Using a
      random effects model, we calculated pooled RRs and 95% CIs. RESULTS: The group
      with the highest postchallenge blood glucose level (midpoint range, 150-194 mg/dL
      [8.3-10.8 mmol/L]) had a 27% greater risk for CVD compared with the group with
      the lowest level (midpoint range, 69-107 mg/dL [3.8-5.9 mmol/L]) (RR, 1.27 [95%
      CI, 1.09-1.48]). The results were similar when combining studies regardless of
      type of blood glucose assessment (RR, 1.36 [95% CI, 1.23-1.52]) and when using
      strict criteria for exclusion of diabetic subjects (RR, 1.26 [95% CI, 1.11
      1.43]). Adjustment for CVD risk factors attenuated but did not abolish this
      relationship (RR, 1.19 [95% CI, 1.07-1.32]). The RR was greater in cohorts
      including women than in cohorts of men (RR, 1.56 vs 1.24 [P = .03]). CONCLUSION:
      Blood glucose level is a risk marker for CVD among apparently healthy individuals
      without diabetes.

PMID- 15505128
TI  - The national cholesterol education program diet vs a diet lower in carbohydrates
      and higher in protein and monounsaturated fat: a randomized trial.
AB  - BACKGROUND: In the United States, obesity is a major clinical and public health
      problem causing diabetes, dyslipidemia, and hypertension, as well as increasing
      cardiovascular and total mortality. Dietary restrictions of calories and
      saturated fat are beneficial. However, it remains unclear whether replacement of
      saturated fat with carbohydrates (as in the US National Cholesterol Education
      Program [NCEP] diet) or protein and monounsaturated fat (as in our isocaloric
      modified low-carbohydrate [MLC] diet, which is lower in total carbohydrates but
      higher in protein, monounsaturated fat, and complex carbohydrates) is optimal.
      METHODS: We randomized 60 participants (29 women and 31 men) to the NCEP or the
      MLC diet and evaluated them every 2 weeks for 12 weeks. They were aged 28 to 71
      years (mean age, 44 years in the NCEP and 46 years in the MLC group). A total of
      36% of participants from the NCEP group and 35% from the MLC group had a body
      mass index (calculated as weight in kilograms divided by the square of height in
      meters) greater than 27. The primary end point was weight loss, and secondary end
      points were blood lipid levels and waist-to-hip ratio. RESULTS: Weight loss was
      significantly greater in the MLC (13.6 lb) than in the NCEP group (7.5 lb), a
      difference of 6.1 lb (P = .02). There were no significant differences between the
      groups for total, low density, and high-density lipoprotein cholesterol,
      triglycerides, or the proportion of small, dense low-density lipoprotein
      particles. There were significantly favorable changes in all lipid levels within
      the MLC but not within the NCEP group. Waist-to-hip ratio was not significantly
      reduced between the groups (P = .27), but it significantly decreased within the
      MLC group (P = .009). CONCLUSIONS: Compared with the NCEP diet, the MLC diet,
      which is lower in total carbohydrates but higher in complex carbohydrates,
      protein, and monounsaturated fat, caused significantly greater weight loss over
      12 weeks. There were no significant differences between the groups in blood lipid
      levels, but favorable changes were observed within the MLC diet group.

PMID- 15505130
TI  - Antibiotics for the secondary prevention of ischemic heart disease: a meta
      analysis of randomized controlled trials.
AB  - BACKGROUND: Infections have been suspected in the pathogenesis of ischemic heart
      disease (IHD) for more than 100 years. Chlamydia pneumoniae has been identified
      in atherosclerotic specimens, and in some studies antibody titers to C pneumoniae
      have been related to the risk of myocardial infarction. The numerous clinical
      trials that have studied the use of antibiotics in the secondary prevention of
      IHD have had conflicting results. METHODS: This study is a meta-analysis of the
      published randomized controlled trials on the secondary prevention of IHD with
      antibiotics. Studies included in the analysis were limited to those studies that
      used antibiotics effective against C pneumoniae, enrolled patients with known
      IHD, and examined clinical outcomes related to IHD. Inclusion in the analysis was
      limited to well-designed randomized controlled trials that met inclusion criteria
      established by an expert panel. RESULTS: Nine published studies, with a total of
      11 015 participants, were identified that met the criteria for this meta
      analysis. Four of the studies reported a benefit from antibiotics, whereas 5
      found no effect. A funnel plot of the published studies did not suggest the
      existence of other unpublished data. The combined effect found no benefit from
      antibiotics in the prevention of cardiovascular events in subjects with known IHD
      (relative risk, 0.94 [95% confidence interval, 0.86-1.03]) or mortality (relative
      risk, 0.94 [95% confidence interval, 0.79-1.12]). CONCLUSION: In patients with
      known IHD, macrolide antibiotics for C pneumoniae did not result in a
      statistically significant reduction in recurrent cardiac events or mortality over
      3 months to 3 years.

PMID- 15505131
TI  - Early withdrawal of statin therapy in patients with non-ST-segment elevation
      myocardial infarction: national registry of myocardial infarction.
AB  - BACKGROUND: There is increasing interest in the non-lipid-lowering effects of
      statins and their effect on outcomes in patients with acute coronary syndrome. It
      has been suggested that withdrawal of statin therapy during an acute coronary
      syndrome may attenuate any benefits of pretreatment, thereby providing indirect
      evidence of the importance of their non-lipid-lowering effects. METHODS: This
      observational study compared the demographic and clinical characteristics and
      hospital outcomes in patients with non-ST-segment elevation myocardial infarction
      enrolled in the National Registry of Myocardial Infarction 4. Comparison groups
      consisted of patients previously receiving statins who also received statins
      within 24 hours of hospital admission (n = 9,001), patients previously using
      statins in whom therapy was discontinued (n = 4,870), and patients who did not
      receive statins at any time before or during hospitalization (n = 54,635).
      RESULTS: Of 13,871 patients receiving statins before hospital admission, 35.1%
      had treatment withdrawn during the first 24 hours of hospitalization. These
      patients had increased hospital morbidity and mortality rates relative to
      patients in whom therapy was continued, with higher rates of heart failure,
      ventricular arrhythmias, shock, and death. In multivariate analyses, these
      patients were at statistically significant increased risk of hospital death
      compared with those continuing statin therapy and at similar risk compared with
      those not receiving statins before or during hospitalization. CONCLUSIONS:
      Withdrawal of statin therapy in the first 24 hours of hospitalization for non-ST
      segment elevation myocardial infarction is associated with worse hospital
      outcomes. In the absence of data from randomized clinical trials, our findings
      suggest that statin therapy should be continued during hospitalization for
      myocardial infarction unless strongly contraindicated.

PMID- 15505132
TI  - Metabolic significance of nonalcoholic fatty liver disease in nonobese,
      nondiabetic adults.
AB  - BACKGROUND: Obesity and type 2 diabetes are well-known risk factors for the
      development of nonalcoholic fatty liver disease (NAFLD). However, NAFLD is not
      rare in nonobese, nondiabetic adults. The aim of this study was to evaluate the
      metabolic significance of NAFLD in nonobese, nondiabetic adults. METHODS: This
      study examined 768 nonobese (body mass index [BMI] [calculated as weight in
      kilograms divided by the square of height in meters], > or =18.5 and <30) (460
      normal-weight and 308 overweight subjects), nondiabetic individuals older than 30
      years who participated in a medical checkup. All the subjects had negative
      serologic findings for hepatitis B and C viruses and had an alcohol intake less
      than 140 g/wk. A standard interview, anthropometrics, a biochemical study, and
      abdominal ultrasonography were conducted. RESULTS: The prevalence of NAFLD in the
      enrolled subjects was 23.4%. In the normal-weight (BMI, > or =18.5 and <25) and
      overweight (BMI, > or =25 and <30) groups, NAFLD was a significant predictor of
      insulin resistance and other metabolic disorders, including hypertriglyceridemia
      and hyperuricemia. The odds ratio of the metabolic disorders in subjects with
      NAFLD compared with those without NAFLD in the normal-weight group was higher
      than that in the overweight group. Multiple logistic regression analysis showed
      that sex, waist circumference, triglyceride level, and insulin resistance were
      independently associated with NAFLD in the normal-weight group. CONCLUSIONS:
      Nonalcoholic fatty liver disease is closely associated with metabolic disorders,
      even in nonobese, nondiabetic subjects. Nonalcoholic fatty liver disease can be
      considered an early predictor of metabolic disorders, particularly in the normal
      weight population.

PMID- 15505133
TI  - International normalized ratio increase before warfarin-associated hemorrhage:
      brief and subtle.
AB  - OBJECTIVE: To determine the relationship between serial international normalized
      ratios (INRs) in patients who have been undergoing long-term anticoagulation and
      the onset of warfarin-associated bleeding complications. METHODS: The study
      cohort consisted of 2391 patients treated in the Anticoagulation Service at
      Brigham and Women's Hospital, Boston, Mass, from April 1999 through July 2003.
      For each patient with a bleeding event, we selected 2 controls who were matched
      for age, sex, indication for warfarin therapy, and duration of enrollment in our
      Anticoagulation Service. RESULTS: Warfarin-related hemorrhage occurred in 32
      patients (1.3%). The mean +/- SD INRs at the time of the bleeding event or
      matched patient's event date (5.9 +/- 5.9 vs 2.3 +/- 0.7; P<.001) and the mean+/
      SD last INRs before the bleeding event or matched patient's event date (3.0 +/-
      1.2 vs 2.1 +/- 0.8; P<.001) were higher in the patients than in the controls. The
      last INRs before the bleeding event were obtained an average of 11.6 +/- 17.8
      (mean +/- SD) days before the event in the patients and 18.3 +/- 28.0 (mean +/-
      SD) days before the matched date in the controls (P = .22). The mean second-to
      last INRs were similar in both groups (2.8 +/- 2.1 vs 2.3 +/- 0.8; P = .11). When
      the INRs were plotted in relation to the time before the onset of bleeding, a
      marked increase in the patients' INRs was observed shortly before the bleeding
      began. CONCLUSIONS: Serial INRs are poor predictors of hemorrhagic events. There
      appears to be only a brief warning period during which a slightly elevated INR
      predicts an imminent bleeding event.

PMID- 15505134
TI  - Sleep and Parkinson Disease. Proceedings of a symposium. March 2003, Naples,
      Italy.

PMID- 15505135
TI  - Akathisia, restless legs and periodic limb movements in sleep in Parkinson's
      disease.
AB  - Restless legs syndrome (RLS) symptoms are often reported in Parkinson's disease
      (PD), but prevalence studies of RLS in PD are few and the results are
      inconsistent. In addition, clinical overlapping between RLS, "wearing-off"
      related lower limb discomfort and restlessness, and akathisia complicate the
      clinical assessments of true RLS in PD. Underlying pathophysiology potentially
      shared by RLS and PD is mainly suggested by similarities in treatment response.
      Functional imaging studies in RLS are still inconclusive, although some authors
      have found subtle deficits in nigrostriatal terminal function. Long-term
      prospective studies of RLS cohorts will clarify whether or not RLS is associated
      with an increased risk for development of PD.

PMID- 15505136
TI  - Clinical assessment of nocturnal disability in Parkinson's disease: the
      Parkinson's Disease Sleep Scale.

PMID- 15505137
TI  - The two faces of Eve: dopamine's modulation of wakefulness and sleep.
AB  - In Parkinson's disease (PD), waking is frequently punctuated by sleep episodes,
      including rapid eye movement (REM) (i.e., dream) sleep, and sleep is interrupted
      by motor activities such as periodic limb movements and REM sleep behavior
      disorder. Because these pathologic behaviors are unaccounted for by contemporary
      models, this review summarizes the complex effects of dopamine (DA) on normal and
      pathological waking-sleeping. Maintenance of wakefulness is probably promoted by
      mesocorticolimbic DA circuits, and suppression of nocturnal movement appears to
      be influenced by indirect pathways linking midbrain DA neurons with pre-motor
      structures in the mesopontine tegmentum and ventromedial medulla. A
      diencephalospinal DA system may have an additional important role in mediating
      state-specific sensorimotor activity that is relevant to periodic limb movements
      and restless legs syndrome.

PMID- 15505138
TI  - How to evaluate excessive daytime sleepiness in Parkinson's disease.
AB  - Excessive daytime sleepiness (EDS) is now recognized as an important problem in
      Parkinson's disease (PD), and its detection and treatment are clinically
      relevant. Several methods are available to evaluate EDS. Subjective methods
      consist of questionnaires to be filled out by the patient and include, among
      others, the Stanford Sleepiness Scale, the Karolinska Sleepiness Scale, and the
      Epworth Sleepiness Scale. These are entirely dependent on the patients'
      perception of their problems. Objective methods evaluate sleepiness indirectly,
      measuring the time it takes for the subject to fall asleep when placed in a
      soporific situation. Two types can be further identified: those using
      electrophysiologic measures [the Multiple Sleep Latency Test (MSLT) and the
      Maintenance of Wakefulness Test (MWT)] and those measuring performance (e.g., the
      Oxford Sleep Resistance test). The Epworth Sleepiness Scale and the MSLT have
      been used repeatedly in PD and, in spite of their limitations, they are, together
      with the MWT, the best available methods to measure EDS in these patients.

PMID- 15505139
TI  - Excessive daytime sleepiness in Parkinson's disease.

PMID- 15505140
TI  - Hallucinations and sleep disturbances in Parkinson's disease.
AB  - Visual hallucinations (VHs) occur frequently in Parkinson's disease (PD). VHs
      occur more frequently in elderly patients with longer duration of illness,
      cognitive impairment, and sleep disturbances. The relationship between the use of
      antiparkinsonian drugs and VHs is complicated, but most drugs used to treat
      parkinsonian motor symptoms induce VHs and psychosis in some PD patients. The
      "continuum hypothesis" proposing that medication-induced psychiatric symptoms in
      PD begin with drug-induced sleep disturbances, followed by vivid dreams, with
      progression to hallucinatory and delusional experiences has been challenged. In
      some patients, VHs may represent intrusion of REM sleep-related imagery into
      wakefulness. Improving REM sleep abnormalities in PD (e.g., stimulants,
      anticholinesterase inhibitors) is one strategy now being tested to improve VHs in
      PD.

PMID- 15505141
TI  - Fluctuations in cognition and alertness in Parkinson's disease and dementia.
AB  - Fluctuations in cognition and alertness (FC/FA) are key manifestations of
      dementia with Lewy bodies (DLB) and also have been recognized recently in
      patients with Parkinson's disease (PD) with dementia, a condition that shares
      important clinical, genetic, and neuropathologic characteristics with DLB. A
      comprehensive assessment of potential episodes of FC/FA is required for adequate
      clinical management, and several interesting clinical instruments are being
      developed for that purpose. FC/FA should be differentiated from episodes of
      excessive daytime sleepiness (EDS). Such diagnostic differentiation appears to be
      necessary, particularly in the light of the different therapeutic approaches to
      FA and EDS. Based on the deficit in cholinergic transmission observed in DLB
      patients, cholinesterase inhibitors, such as rivastigmine, may have a beneficial
      effect on FC/FA. Other therapies, such as melatonin or modafinil, require further
      investigation.

PMID- 15505142
TI  - Treatment of nocturnal disturbances and excessive daytime sleepiness in
      Parkinson's disease.
AB  - Nocturnal disturbances are common in Parkinson's disease (PD) patients, with
      almost 70% of these patients reporting nocturnal disturbances. The etiology of
      sleep disturbances in patients with PD is still controversial. They might be
      dependent on dopaminergic drugs, on disease progression, or on a combination of
      these two factors. Nocturnal disturbances can be categorized in four groups: 1)
      PD-related motor symptoms, including nocturnal akinesia, early-morning dystonia,
      painful cramps, tremor, and difficulty turning in bed; 2) treatment-related
      nocturnal disturbances; 3) psychiatric symptoms, including hallucinations, vivid
      dreams, depression, dementia, insomnia, psychosis, and panic attacks; 4) other
      sleep disorders, including insomnia, REM behavioral disorder (RBD), restless legs
      syndrome (RLS), periodic leg movements (PLMS), and excessive daytime sleepiness
      (EDS). Specific treatment options are supplied for every group. A global
      evaluation of nocturnal disturbances would provide clinicians with a valuable
      tool to establish an optimal regimen that could positively influence all
      nocturnal disturbance categories and thus improve PD management on. However, it
      is important to consider that management of some nocturnal disturbances in a
      group may worsen nocturnal symptoms of another group or may increase EDS. PD
      related symptoms can be treated with long-acting DA agonists to obtain continuous
      DA receptor stimulation during the night. Both treatment-related nocturnal
      disturbances and psychiatric symptoms may be related to drug treatment, and
      therefore, in both cases, drug reduction or discontinuance should be considered.
      Some sleep disorders, such as RLS and PLMS, may be controlled by DA agents, and
      others, such as insomnia and EDS, may be improved by reducing dopaminergic
      stimulation.

PMID- 15505143
TI  - Nocturnal problems occurring in Parkinson's disease.
AB  - A large number of patients with Parkinson's disease (PD) experience nocturnal
      problems that impair their sleep quality. Among them, motor disorders such as
      tremor, rigidity, akinesia, akathisia, periodic leg movements, painful dystonia,
      dyskinesias, restless legs syndrome, and rapid eye movement sleep behavior
      disorder are common. This article reviews the clinical characteristics of some
      nocturnal motor problems that often induce sleep disruption in PD patients.

PMID- 15505145
TI  - NIFID: a new molecular pathology with a frontotemporal dementia phenotype.

PMID- 15505146
TI  - What does PINK1 mean for Parkinson diseases?

PMID- 15505147
TI  - Subacute sclerosing panencephalitis: a preventable disease that needs to be
      prevented.

PMID- 15505148
TI  - An AUPN/ANA survey of department leader opinions on the health of US academic
      neurology.
AB  - The Association of University Professors of Neurology and the American Neurologic
      Association surveyed the leaders of academic neurology programs in the United
      States to assess the current financial health of academic neurology. The survey,
      completed in late 2002, addressed program relations with hospitals and medical
      schools and the effects of financial pressures on program operations, clinical
      responsibilities, research, teaching, and faculty development. Response patterns
      suggest academic neurology is challenged on several levels and indicate a need
      for strategic reflection and focused research to better gauge the state of
      neurology in the United States and to develop solutions for program survival and
      evolution.

PMID- 15505149
TI  - Oral antispastic drugs in nonprogressive neurologic diseases: a systematic
      review.
AB  - OBJECTIVE: To assess the efficacy of oral drugs in the treatment of spasticity in
      patients with nonprogressive neurologic disease (NPND). METHODS: Systematic
      review of double-blind randomized controlled trials of antispastic oral drugs in
      the treatment of spasticity in NPND. DATA SOURCES: Electronic MEDLINE, PubMed,
      Cochrane Library, and hand searches. RESULTS: Twelve studies (469 patients) were
      included (6 on stroke, 3 on spinal cord diseases, and 3 on cerebral palsy).
      Tizanidine was assessed in four trials (276 patients, 142 exposed), dantrolene in
      four (103, 93), baclofen in three (70, 55), diazepam in two (127, 76), and
      gabapentin in one (28, all exposed). Most trials were of small size, of short
      duration, and their methodologic quality was inadequate. Ten trials were
      controlled with placebo and only two were direct comparisons between drugs.
      Efficacy outcome variables were heterogeneous. Only four reports described the
      magnitude of the antispastic effect. The incidence of adverse drug effects
      (drowsiness, sedation, and muscle weakness) was high. CONCLUSION: Evidence on the
      efficacy of oral antispastic drugs in NPND is weak and does not include
      evaluation of patients' quality of life. If any, efficacy is marginal. Adverse
      drug reactions were common. Better methodologic instruments are needed for the
      evaluation of antispastic treatment.

PMID- 15505150
TI  - Treatment of pseudobulbar affect in ALS with dextromethorphan/quinidine: a
      randomized trial.
AB  - BACKGROUND: Patients with ALS commonly exhibit pseudobulbar affect. METHODS: The
      authors conducted a multicenter, randomized, double-blind, controlled, parallel,
      three-arm study to test a defined combination of dextromethorphan hydrobromide
      (DM) and quinidine sulfate (Q) (AVP-923) for the treatment of pseudobulbar affect
      in ALS. Q inhibits the rapid first-pass metabolism of DM. The effects of AVP-923
      (30 mg of DM plus 30 mg of Q) given twice daily for 28 days were compared with
      those of its components. Patients were evaluated on days 1, 15, and 29. The
      primary efficacy variable was the change from baseline in the Center for
      Neurologic Study Lability Scale (CNS-LS) score. Secondary efficacy variables were
      laughing/crying episode rates and changes in Visual Analog Scales for Quality of
      Life (QOL) and Relationships (QOR). Efficacy was evaluated in intention-to-treat
      subjects who were not poor metabolizers of DM (n = 65 for AVP-923, n = 30 for DM,
      and n = 34 for Q). Safety was assessed in all randomized subjects (n = 140).
      RESULTS: AVP-923 patients experienced 3.3-point greater improvements in CNS-LS
      than DM patients (p = 0.001) and 3.7-point greater improvements than Q patients
      (p < 0.001). AVP-923 patients exhibited lower overall episode rates, improved QOL
      scores, and improved QOR scores (p < 0.01 for all endpoints). Adverse effects
      were mostly mild or moderate; treatment-related discontinuation was 24% for AVP
      923, 6% for DM, and 8% for Q. CONCLUSIONS: AVP-923 palliates pseudobulbar affect
      in ALS. Overall benefits of treatment are reflected in fewer episodes of crying
      and laughing and improvements in overall quality of life and quality of
      relationships.

PMID- 15505151
TI  - Botulinum toxin effect on salivary flow rate in children with cerebral palsy.
AB  - OBJECTIVE: To investigate the effectiveness of botulinum neurotoxin (BoNT) type A
      in reducing salivary flow rate in children with cerebral palsy (CP) with severe
      drooling. METHODS: During a controlled clinical trial, single-dose BoNT
      injections into the submandibular salivary glands were compared with scopolamine
      treatment. Forty-five school-aged children were included. Salivary flow rates
      from all major glands were obtained at baseline and compared with measurements
      during the interventions. Basic statistics consisted of analysis of difference
      scores. RESULTS: Compared with baseline, the mean decrease in submandibular flow
      was 25% during scopolamine and 42% following BoNT injections. The difference
      scores were significant with maximum reductions 2, 4, and 8 weeks following BoNT.
      Of all children, 95% responded during scopolamine. Response rates for BoNT were
      significantly lower and varied from 69% at 2 weeks to 49% at 24 weeks after
      injection (the end of the study). Four patients discontinued scopolamine therapy
      because of side effects. Only incidentally mild side effects were reported from
      BoNT. CONCLUSIONS: Intraglandular BoNT injections significantly reduce salivary
      flow rate in the majority of drooling CP children, demonstrating high response
      rates up to 24 weeks. The procedure is simple to perform, effective, and safe
      when ultrasound guidance is used. The anticholinergic effect of BoNT exceeds that
      of scopolamine. As anticholinergic drugs are frequently contraindicated because
      of side effects, BoNT injections offer an alternative in the treatment of
      drooling.

PMID- 15505152
TI  - Clinical and neuropathologic variation in neuronal intermediate filament
      inclusion disease.
AB  - BACKGROUND: Recently described neuronal intermediate filament inclusion disease
      (NIFID) shows considerable clinical heterogeneity. OBJECTIVE: To assess the
      spectrum of the clinical and neuropathological features in 10 NIFID cases.
      METHODS: Retrospective chart and comprehensive neuropathological review of these
      NIFID cases was conducted. RESULTS: The mean age at onset was 40.8 (range 23 to
      56) years, mean disease duration was 4.5 (range 2.7 to 13) years, and mean age at
      death was 45.3 (range 28 to 61) years. The most common presenting symptoms were
      behavioral and personality changes in 7 of 10 cases and, less often, memory loss,
      cognitive impairment, language deficits, and motor weakness. Extrapyramidal
      features were present in 8 of 10 patients. Language impairment, perseveration,
      executive dysfunction, hyperreflexia, and primitive reflexes were frequent signs,
      whereas a minority had buccofacial apraxia, supranuclear ophthalmoplegia, upper
      motor neuron disease (MND), and limb dystonia. Frontotemporal and caudate atrophy
      were common. Histologic changes were extensive in many cortical areas, deep gray
      matter, cerebellum, and spinal cord. The hallmark lesions of NIFID were unique
      neuronal IF inclusions detected most robustly by antibodies to neurofilament
      triplet proteins and alpha-internexin. CONCLUSION: NIFID is a neuropathologically
      distinct, clinically heterogeneous variant of frontotemporal dementia (FTD) that
      may include parkinsonism or MND. Neuronal IF inclusions are the neuropathological
      signatures of NIFID that distinguish it from all other FTD variants including FTD
      with MND and FTD tauopathies.

PMID- 15505153
TI  - Protein markers for Alzheimer disease in the frontal cortex and cerebellum.
AB  - OBJECTIVE: To compare proteins related to Alzheimer disease (AD) in the frontal
      cortex and cerebellum of subjects with early-onset AD (EOAD) with or without
      presenilin 1 (PS1) mutations with sporadic late-onset AD (LOAD) and nondemented
      control subjects. METHODS: Immunohistochemistry, immunoblot analysis, and ELISA
      were used to detect and assess protein levels in brain. RESULTS: In EOAD and to a
      lesser extent in LOAD, there was increased amyloid beta (Abeta) deposition (by
      immunohistochemistry), increased soluble Abeta (by immunoblot analysis), and
      specific increases in Abeta40 and Abeta42 (by ELISA) in the frontal cortex and,
      in some cases, in the cerebellum. Surprisingly, immunoblot analysis revealed
      reduced levels of PS1 in many of the subjects with EOAD with or without PS1
      mutations. In those PS1 mutation-bearing subjects with the highest Abeta, PS1 was
      barely, if at all, detectable. This decrease in PS1 was specific and not
      attributable solely to neuronal loss because amyloid precursor protein (APP) and
      the PS1-interacting protein beta-catenin levels were unchanged. CONCLUSIONS: This
      study shows that in the frontal cortex and cerebellum from Alzheimer disease
      patients harboring certain presenilin 1 mutations, high levels of amyloid beta
      are associated with low levels of presenilin 1. The study provides the premise
      for further investigation of mechanisms underlying the downregulation of
      presenilin 1, which may have considerable pathogenic and therapeutic relevance.

PMID- 15505155
TI  - APOE epsilon4 and cognitive decline in older stroke patients with early cognitive
      impairment.
AB  - BACKGROUND: Dementia is common post stroke, but the potential role of early
      cognitive impairment and APOE epsilon4 as risk factors is unclear. METHOD: Stroke
      survivors older than 75 years without dementia at 3 months post stroke received a
      detailed neuropsychological evaluation at 3 and 15 months post stroke, which
      included the Cambridge Assessment of Mental Disorders in the Elderly (CAMCOG).
      Early cognitive impairment was diagnosed using the criteria for cognitive
      impairment/no dementia (vascular CIND). APOE genotype was determined using a
      standardized method. RESULTS: One hundred thirty-seven older stroke patients
      without dementia (mean age 80.6 +/- 4.3, mean CAMCOG score 83.5 +/- 10.4, 68
      women) participated in the study, of whom 40 met the criteria for CIND. Stroke
      patients with one or more APOE epsilon4 alleles were significantly more likely to
      have CIND (14/40 vs 17/97, odds ratio = 2.5, 95% CI 1.1 to 5.8). Over the 1 year
      of follow-up, CIND patients with one or more APOE epsilon4 alleles had a mean
      decline on the total CAMCOG of 2.7 points compared with an improvement of >4
      points among patients without APOE epsilon4 (T = 2.9 p = 0.006). CIND patients
      with an APOE epsilon4 allele also experienced greater decline in memory (T = 2.5,
      p = 0.015). CONCLUSION: In older stroke patients with early cognitive impairment,
      the presence of an APOE epsilon4 allele is associated with greater progression of
      cognitive decline. This has implications for interventions aimed at the secondary
      prevention of dementia in stroke patients.

PMID- 15505154
TI  - 1H MR spectroscopy in common dementias.
AB  - OBJECTIVE: To determine the 1H MR spectroscopic (MRS) findings and intergroup
      differences among common dementias: Alzheimer disease (AD), vascular dementia
      (VaD), dementia with Lewy bodies (DLB), and frontotemporal lobar degeneration
      (FTLD). METHODS: The authors consecutively recruited 206 normal elderly subjects
      and 121 patients with AD, 41 with FTLD, 20 with DLB, and 8 with VaD. The 1H MRS
      metabolite ratio changes in common dementias were evaluated with respect to
      normal and also differences among the common dementias. RESULTS: N
      acetylaspartate (NAA)/creatine (Cr) was lower than normal in patients with AD,
      FTLD, and VaD. Myo-inositol (mI)/Cr was higher than normal in patients with AD
      and FTLD. Choline (Cho)/Cr was higher than normal in patients with AD, FTLD, and
      DLB. There were no metabolite differences between patients with AD and FTLD or
      between patients with DLB and VaD. NAA/Cr was lower in patients with AD and FTLD
      than DLB. MI/Cr was higher in patients with AD and FTLD than VaD. MI/Cr was also
      higher in patients with FTLD than DLB. CONCLUSIONS: NAA/Cr levels are decreased
      in dementias that are characterized by neuron loss, such as AD, FTLD, and VaD.
      MI/Cr levels are elevated in dementias that are pathologically characterized by
      gliosis, such as AD and FTLD. Cho/Cr levels are elevated in dementias that are
      characterized by a profound cholinergic deficit, such as AD and DLB.

PMID- 15505156
TI  - fMRI language task panel improves determination of language dominance.
AB  - BACKGROUND: fMRI language tasks reliably identify language areas in presurgical
      epilepsy patients, but activation using single paradigms may disagree with the
      intracarotid amobarbital test (IAT). OBJECTIVE: To determine whether a panel of
      fMRI tasks targeting different aspects of language processing increases accuracy
      in determining hemisphere language dominance. METHODS: Twenty-six patients age 12
      to 56 years, predominantly with temporal lobe epilepsy, were studied using whole
      brain 1.5 T fMRI (echo planar imaging, blood oxygenation level-dependent) with
      three task categories using a block design: verbal fluency, reading
      comprehension, and auditory comprehension. fMRI t maps were visually rated at
      three thresholds. All patients had assessment of language lateralization by IAT.
      RESULTS: fMRI showed left dominance in 21 patients, right dominance in 2, and
      bilateral activation in 2; raters disagreed over a left vs right bilateral rating
      in 1 patient. There was full agreement between IAT and fMRI in 21 of 25 patients
      (IAT failed in 1). In three instances of partial disparity with IAT, the fMRI
      panel showed consistent findings across raters. Agreement between raters was
      excellent (partial disagreement in only one patient); the panel of tasks was
      superior to any single task for interrater agreement (Cramer V 0.93 [range 0.91
      to 1.0] vs 0.72 [range 0.60 to 0.86]). CONCLUSIONS: A panel of fMRI language
      paradigms may be more accurate for evaluating partial epilepsy patients than a
      single task. A panel of tasks reduces the likelihood of nondiagnostic findings,
      improves interrater reliability, and helps confirm language laterality.

PMID- 15505157
TI  - Altered cortical visual processing in PD with hallucinations: an fMRI study.
AB  - OBJECTIVE: To compare fMRI activation during two visual stimulation paradigms in
      Parkinson disease (PD) subjects with chronic visual hallucinations vs PD patients
      who had never hallucinated. METHODS: Twelve pairs of PD subjects, matched for
      age, PD duration, and dopaminergic drug exposure duration, participated in this
      study. The authors examined group differences in activation during stroboscopic
      (flashing) vs no visual stimulation and kinematic (apparent motion) vs stationary
      visual stimulation. RESULTS: During stroboscopic stimulation, non-hallucinating
      PD subjects showed significantly greater activation in the parietal lobe and
      cingulate gyrus compared to hallucinating PD subjects. In contrast, the
      hallucinating subjects showed significantly greater activation in the inferior
      frontal gyrus and the caudate nucleus. During kinematic stimulation, non
      hallucinating PD subjects showed significantly greater activation in area V5/MT,
      parietal lobe, and cingulate gyrus compared to hallucinating PD subjects.
      Hallucinating PD subjects showed significantly greater activation in the superior
      frontal gyrus. CONCLUSIONS: PD patients with chronic visual hallucinations
      respond to visual stimuli with greater frontal and subcortical activation and
      less visual cortical activation than non-hallucinating PD subjects. Shifting
      visual circuitry from posterior to anterior regions associated primarily with
      attention processes suggests altered network organization may play a role in the
      pathophysiology of visual hallucinations in PD.

PMID- 15505158
TI  - A multimodal assessment of driving performance in HIV infection.
AB  - OBJECTIVE: To examine if HIV-seropositive (HIV+) individuals are at risk for
      impaired driving. METHODS: Sixty licensed drivers (40 HIV+, 20 HIV-) completed a
      neuropsychological (NP) test battery and driving assessments. Eleven HIV+
      subjects were NP-impaired. Driving-related skills were assessed using 1) two
      driving simulations (examining accident avoidance and navigational abilities), 2)
      the Useful Field of View (UFOV) test, and 3) an on-road evaluation. RESULTS: HIV+
      NP-impaired subjects had greater difficulty than cognitively intact subjects on
      all driving measures, whereas the HIV- and HIV+ NP-normal groups performed
      similarly. On the UFOV, the HIV+ NP-impaired group had worse performance on
      Visual Processing and Divided Attention tasks but not in overall risk
      classification. They also had a higher number of simulator accidents (1.3 vs 2.0;
      p = 0.03), were less efficient at completing the navigation task (3.2 vs 9.2
      blocks; p = 0.001), and were more likely to fail the on-road evaluation (6 vs
      36%; p = 0.02). Impairment in Executive Functioning was the strongest NP
      predictor of failing the on-road drive test. NP performance and both simulations
      independently contributed to a model predicting 48% of the variance in on-road
      performance. CONCLUSION: HIV+ NP-impaired individuals are at increased risk for
      on-road driving impairments, whereas HIV+ individuals with normal cognition are
      not at a significantly higher risk than HIV- subjects. Executive Functioning is
      most strongly associated with impaired on-road performance. Cognitive and
      simulator testing may each provide data in identifying driving-impaired
      individuals.

PMID- 15505159
TI  - Age at onset as a factor in determining the phenotype of primary torsion
      dystonia.
AB  - BACKGROUND: The genetic basis of most forms of primary torsion dystonia (PTD) is
      unknown; multiplex families are uncommon due to low penetrance. Intrafamilial,
      age-related, phenotypic heterogeneity was noted in 14 PTD families. The authors
      hypothesized that the clinical presentation of PTD was modulated by the age at
      onset of the dystonia, irrespective of the genotype. METHODS: This hypothesis was
      addressed in a study of 14 PTD families and a meta-analysis of 83 published
      series of PTD. RESULTS: In 12 families with adult-onset PTD, the index cases
      presented with cervical dystonia (CD); of the 22 affected relatives, 17 had CD, 2
      had writer's cramp, 1 had blepharospasm, and 2 had spasmodic dysphonia. In the
      two other PTD families, the probands and all 10 symptomatic relatives had limb
      onset dystonia at <20 years of age. There were differences between the median
      ages at onset of the different phenotypes (p = 0.0037). Analysis of 83 published
      series including 5,057 patients indicated significant differences in the mean age
      at onset of five phenotypes of PTD (mean age at onset; 95% CI): DYT1 dystonia
      (11.3 years; 10.3 to 12.2), writer's cramp (38.4; 36.9 to 39.9), CD (40.8; 40.3
      to 41.3), spasmodic dysphonia (43.0; 42.2 to 43.9), and blepharospasm
      oromandibular dystonia (55.7; 55.1 to 56.4). CONCLUSION: Phenotypic variation in
      PTD presentation is due to the effect of age at onset modulating the expression
      of a genetic disorder with a caudal-to-rostral change in the site of onset.

PMID- 15505160
TI  - Sympathetic and parasympathetic baroreflex dysfunction in familial dysautonomia.
AB  - OBJECTIVE: To assess the possible abnormalities in the baroreflex modulation of
      both the heart and the arterial vasculature, in order to better evaluate the role
      of baroreflex abnormalities in the generation of the cardiovascular symptoms and
      complications affecting the familial dysautonomia (FD) patient. METHODS: Twenty
      one FD patients and 22 controls underwent 3 minutes of passive head-up tilt (HUT)
      and baroreceptor stimulation by means of sinusoidal neck suction (NS; 0 to -30 mm
      Hg; 0.1 Hz [LF] and 0.2 Hz [HF]). Respiration was maintained constant during NS
      at 15 breaths/minute. The authors monitored RR-intervals (RRI), blood pressure
      (BP) (Colin), and respiration. NS induced changes of RRI and BP were determined
      by spectral analysis. RESULTS: HUT showed orthostatic hypotension without
      compensatory tachycardia in FD patients but not in controls. LF-NS increased LF
      power of RRI and BP and HF-NS increased HF power of RRI in controls, but not in
      FD patients. CONCLUSIONS: Familial dysautonomia patients have a widespread
      baroreflex abnormality, involving both the efferent sympathetic arm on the
      resistance vessels, and the sympathetic and parasympathetic efferent arms on the
      heart. Therefore, the abnormalities in the control of blood pressure-i.e., supine
      hypertension, orthostatic hypotension, blood pressure lability-and heart rate
      i.e., bradyarrhythmias-are likely due to baroreflex abnormalities.

PMID- 15505161
TI  - Prevalence and impact of migraine and probable migraine in a health plan.
AB  - BACKGROUND: A large number of headache sufferers with features of migraine fail
      to meet criteria for strict migraine (SM; migraine with or without aura) but do
      meet criteria for probable migraine (PM). OBJECTIVES: To estimate the prevalence
      of PM, to compare the epidemiologic profiles of SM and PM, and to assess the
      disability and impact on the health-related quality of life (HRQoL) of these
      patients. METHODS: Computer-assisted telephone interviews in a sample recruited
      from a mixed model health maintenance organization were used. SM, PM, and control
      subjects were identified. Also assessed were demographic features, disability,
      HRQoL, and depression. RESULTS: The 1-year prevalence for SM was 14.7% (19.2% in
      women and 6.6% in men); for PM, it was 14.6% (15.9% in women, 12.6% in men). Most
      subjects with PM (82%) did not meet the associated symptom criteria for migraine.
      HRQoL was reduced in the PM, SM, and all migraine (AM; SM and PM pooled together)
      groups compared with controls. The proportion of subjects with high disability
      was elevated in PM (13%), SM (31%), and AM (22%) groups vs controls (3.7%; p <
      0.0001). CONCLUSIONS: Within a health plan, probable migraine is a prevalent form
      of migraine, with symptom and epidemiologic profiles that overlap with strict
      migraine. Although strict migraine prevalence was consistent with previous
      studies, a probable migraine prevalence higher than previously reported was
      found, perhaps reflecting a difference between health plan and population
      samples.

PMID- 15505162
TI  - CSF nitric oxide metabolites are associated with activity and progression of
      multiple sclerosis.
AB  - OBJECTIVE: To investigate the relationship of CSF and the serum nitric oxide
      metabolites nitrite and nitrate (NOx) to disease activity and progression in
      patients with multiple sclerosis (MS). METHODS: The study was divided into cross
      sectional and follow-up. In the cross-sectional study, 20 patients with relapsing
      remitting (RR), 21 with secondary progressive (SP), and 10 with primary
      progressive (PP) MS and 14 control subjects were included. Patients were assessed
      on clinical (Expanded Disability Status Scale [EDSS], Ambulation Index [AI], 9
      Hole Peg Test [9-HPT]) and MRI measurements. In the follow-up study, 34 MS
      patients from the cross-sectional study agreed to be assessed again after an
      average of 3.0 +/- 0.5 years. NOx was measured using a vanadium-based assay.
      RESULTS: In the cross-sectional study, CSF NOx was raised in patients with RR-MS
      (p = 0.001) and PP-MS (p = 0.02) vs controls. Higher CSF NOx levels were found in
      patients with mild disability (AI < or = 6.0; EDSS < or = 4.0; Multiple Sclerosis
      Severity Score [MSSS] < or = 4.8) vs patients with advanced disease (AI > 6.0 [p
      = 0.002]; EDSS > 4.0 [p = 0.02]; MSSS > 4.8 [p = 0.01]). In the subgroup of
      patients having Gd-enhancing MRI lesions (n = 11), correlation between the volume
      of enhancement and CSF NOx was found (r = 0.74, p = 0.01). In the follow-up
      study, patients with disability progression had higher baseline CSF NOx levels
      than those who were stable on EDSS (p = 0.02) or AI (p = 0.03). A positive
      correlation was found between baseline CSF NOx and the change in MR T2-weighted
      lesion load (r = 0.4, p = 0.03). CONCLUSIONS: CSF nitrite and nitrate levels were
      increased in mildly disabled patients with MS and found to correlate with the
      volume of Gd-enhanced lesions on MRI. Raised baseline CSF NOx was associated with
      clinical and MRI progression in MS patients over 3-year follow-up.

PMID- 15505163
TI  - Elevated pro-inflammatory CD4+CD28- lymphocytes and stroke recurrence and death.
AB  - OBJECTIVE: To determine if the CD4+CD28- T-cell subset is expanded in patients
      with recurrent stroke or death after acute ischemic stroke. This subset of the
      peripheral blood T-cell lymphocyte population has a strong pro-inflammatory and
      tissue-damaging potential. METHODS: Consecutive patients within the first 48
      hours of ischemic stroke were prospectively studied. Peripheral blood CD4+CD28-
      cells were quantified by flow cytometry. The study endpoint was recurrent stroke
      or death from any cause during 1 year of follow-up. RESULTS: One hundred six
      patients (mean age 75.0 +/- 13.5 years; 50 women) were studied. The median
      CD4+CD28- cell count was 4.5% (range 0.2 to 72.2%). Twenty-seven endpoints (10
      recurrent strokes and 17 deaths) occurred during follow-up. Stroke
      recurrence/death rates were significantly associated with increasing CD4+CD28-
      counts, rising from 14.2% in patients with CD4+CD28- levels of <1.0 to 48.1% for
      those with CD4+CD28- counts of >8.0% (p = 0.003, Cochran linear test of trend).
      Higher CD4+CD28- counts were also present in patients with a history of prior
      stroke (p = 0.03). After adjustment for age, admission NIH Stroke Scale score,
      prior stroke, and atrial fibrillation, CD4+CD28- counts of >8.0% were associated
      with a cumulative hazard ratio of 5.81 (95% CI: 1.58 to 21.32) for stroke
      recurrence or death. CONCLUSIONS: Rising counts of circulating CD4+CD28- cells
      are associated with an increasing risk of stroke recurrence and death, in
      addition to an observed association with prior stroke. Expansion of this T-cell
      subset presumably represents a biomarker and possibly a contributory pathogenic
      mechanism of recurrent stroke and death after ischemic stroke.

PMID- 15505164
TI  - A fetal circle of Willis is associated with a decreased deep white matter lesion
      load.
AB  - OBJECTIVE: To investigate the relationship between morphologic differences in the
      circle of Willis and the presence and location of white matter lesions (WMLs).
      METHODS: Two hundred forty-three consecutive patients with clinical
      manifestations of atherosclerotic disease underwent MRI of the brain and MR
      angiography of the circle of Willis. RESULTS: Subjects with a fetal configuration
      of the circle of Willis demonstrated a decreased load of small (p < 0.01) and
      medium (p < 0.01) deep WMLs compared with subjects with a nonfetal configuration
      of the posterior part of the circle of Willis. CONCLUSION: A fetal configuration
      of the posterior part of the circle of Willis may be an important protecting
      determinant in the etiology of white matter lesions.

PMID- 15505165
TI  - Subependymal giant cell tumors in tuberous sclerosis complex.
AB  - OBJECTIVES: To describe the clinical presentations, radiologic features, and
      postoperative outcomes of a clinic-based population of patients with subependymal
      giant cell tumors (SGCT) and tuberous sclerosis complex (TSC) and to redefine and
      reclassify SGCT based on radiologic, clinical, and pathologic criteria. METHODS:
      Of 134 TSC patients evaluated from December 2001 to November 2003, 11 (8.2%) had
      undergone resection of a pathologically confirmed SGCT. The authors reviewed the
      medical records of each case. Follow-up ranged from 2 months to 36 years.
      RESULTS: Four were asymptomatic at the time of resection while the other seven
      presented subacutely with fatigue, decreased appetite, headache, increased
      seizure frequency, visual field deficit, cognitive decline, or behavioral
      problems. Poor outcomes occurred in all patients aged 11 years or older at the
      time of resection. CONCLUSIONS: Subependymal giant cell tumors in patients with
      TSC appear to be of mixed glioneuronal lineage, and, therefore, the current
      practice of classifying these tumors as astrocytomas merits revision. The
      clinical diagnosis of SGCT should be made for subependymal lesions in TSC that
      are associated with symptoms, papilledema, or radiologic evidence of
      hydrocephalus or interval growth. A diagnosis of probable SGCT should be made
      when a lesion has the potential to cause obstruction based on size or location.
      Annual screening by MRI with or without contrast is indicated until at least 21
      years of age even if subependymal nodules are absent on initial imaging. A
      diagnosis of SGCT or probable SGCT warrants more frequent monitoring or surgical
      intervention.

PMID- 15505166
TI  - A controlled study of peripheral neuropathy after bariatric surgery.
AB  - BACKGROUND: Although peripheral neuropathy (PN) occurs after bariatric surgery
      (BS), a causal association has not been established. OBJECTIVES: To ascertain
      whether PN occurs more frequently following BS vs another abdominal surgery, to
      characterize the clinical patterns of PN, to identify risk factors for PN, and to
      assess if nerve biopsy provides pathophysiologic insight. METHODS: Retrospective
      review identified patients with PN after BS. The frequency of PN was compared
      with that of an age- and gender-matched, retrospectively evaluated cohort of
      obese patients undergoing cholecystectomy. RESULTS: Of 435 patients who had BS,
      71 (16%) developed PN. Patients developed PN more often after BS than after
      cholecystectomy (4/126; 3%) (p < 0.001). The clinical patterns of PN were
      polyneuropathy (n = 27), mononeuropathy (n = 39), and radiculoplexus neuropathy
      (n = 5). Risk factors included rate and absolute amount of weight loss, prolonged
      gastrointestinal symptoms, not attending a nutritional clinic after BS, reduced
      serum albumin and transferrin after BS, postoperative surgical complications
      requiring hospitalization, and having jejunoileal bypass. Most risk factors were
      associated with the polyneuropathy group. Sural nerve biopsies showed prominent
      axonal degeneration and perivascular inflammation. CONCLUSIONS: Peripheral
      neuropathy (PN) occurs more frequently after bariatric surgery (BS) than after
      another abdominal surgery. The three clinical patterns of PN after BS are sensory
      predominant polyneuropathy, mononeuropathy, and radiculoplexus neuropathy.
      Malnutrition may be the most important risk factor, and patients should attend
      nutritional clinics. Inflammation and altered immunity may play a role in the
      pathogenesis, but further study is needed.

PMID- 15505167
TI  - Painful sweating.
AB  - OBJECTIVE: The authors report a case of spontaneous and gustatory facial pain and
      sweating. METHODS: The patient had frequent episodes of pain, sweating, and
      flushing bilaterally in the hairless skin of the ophthalmic and maxillary
      distributions of the trigeminal nerve. Gustatory stimuli (e.g., orange juice,
      pickled onions) reliably evoked episodes, but episodes also frequently came on
      spontaneously. The problem had begun during adolescence, about the time of
      topical treatment and then electrocauteries for facial warts. The patient
      reported benefit from tricyclic antidepressants, guanethidine, and trospium
      chloride (an anti-cholinergic quaternary amine used in Europe for urinary
      urgency). There was no pain or excessive sweating in other body areas, nor pain
      with exercise. RESULTS: Administration of edrophonium IV evoked pain and
      sweating, and ganglion blockade by IV trimethaphan eliminated pain and sweating
      and markedly attenuated responses to edrophonium. Trospium chloride also
      prevented edrophonium-induced pain and sweating. Bicycle exercise produced the
      same increment in forehead humidity as in a spontaneous episode but did not evoke
      pain. Tyramine infusion did not bring on pain or sweating, whereas iontophoretic
      acetylcholine administration to one cheek evoked pain and sweating bilaterally.
      Topical glycopyrrolate cream eliminated spontaneous, gustatory, and edrophonium
      induced episodes. CONCLUSIONS: The findings indicate that facial pain and
      sweating can result from occupation of muscarinic cholinergic receptors after
      acetylcholine release from local nerves. The authors propose that after
      destruction of cutaneous nerves, aberrant regenerant sprouting innervates sweat
      glands, producing gustatory sweating as in auriculotemporal syndrome (Frey
      syndrome), and innervates nociceptors, producing pain.

PMID- 15505168
TI  - Idiopathic pure sudomotor failure: anhidrosis due to deficits in cholinergic
      transmission.
AB  - BACKGROUND: Acquired idiopathic generalized anhidrosis (AIGA) represents a
      heterogeneous clinical syndrome including sudomotor neuropathy and failure of the
      sweat glands. However, most AIGA cases comprise idiopathic pure sudomotor failure
      (IPSF), a distinct subgroup without sudomotor neuropathy or sweat gland failure.
      METHODS: Eight patients with IPSF (mean +/- SD age 20 +/- 5 years) were assessed
      by thermoregulatory and pilocarpine-induced sweating tests, as well as emotional
      sweating using sudorometer (4 cases), microneurography of skin sympathetic nerve
      activity (2 cases), and skin biopsies from the forearm or axilla (3 cases).
      RESULTS: Clinical features of IPSF comprise early onset; acute or sudden onset;
      concomitant sharp pain or cholinergic urticaria over the entire body; lack of
      autonomic dysfunction other than generalized anhidrosis; elevated serum IgE
      levels; and marked response to steroid. Sudomotor function testing revealed
      complete absence of thermoregulatory sweating, but well-preserved emotional
      sweating; pilocarpine did not induce sweating, and microneurography revealed that
      bursts of skin sympathetic nerve activity were not decreased; and skin biopsy
      displayed no morphologic abnormalities in sweat glands. The first two findings
      suggest lesions on the postsynaptic side of the nerve-sweat gland junction.
      CONCLUSION: The lesions in IPSF may be in the muscarinic cholinergic receptors of
      sweat glands. Allergic mechanisms are probably involved in its pathophysiology.

PMID- 15505169
TI  - Hypertrophic cranial nerve roots in CIDP.

PMID- 15505170
TI  - PARK6-linked autosomal recessive early-onset parkinsonism in Asian populations.
AB  - The authors performed linkage analysis in 39 families with autosomal recessive
      early-onset PD (AR-EOPD) negative for parkin and DJ-1 mutations. Eight families
      including three Japanese, two Taiwanese, one Turkish, one Israeli, and one
      Philippine showed evidence of linkage with PARK6 with multipoint log of the odds
      (lod) score of 9.88 at D1S2732. The results indicate worldwide distribution of
      PARK6-linked parkinsonism.

PMID- 15505171
TI  - PINK1 (PARK6) associated Parkinson disease in Ireland.
AB  - Mutations in the PINK1 gene have recently been shown to cause autosomal recessive
      Parkinson disease (PD). The authors assessed the prevalence of PINK1 gene
      mutations in 290 well-characterized early- and late-onset PD patients from
      Ireland. In a 51-year-old PD patient with a family history of PD, the authors
      identified a novel heterozygous mutation (R147H) in exon 2 of the PINK1 gene.
      Overall, these data indicate that PINK1 mutations are a rare cause of PD in
      Ireland.

PMID- 15505172
TI  - Subacute sclerosing panencephalitis in the differential diagnosis of
      encephalitis.
AB  - The authors describe five cases of subacute sclerosing panencephalitis (SSPE)
      identified through the California Encephalitis Project that emphasize the
      importance of considering SSPE in the differential diagnosis of encephalitis,
      particularly among pediatric patients. SSPE was not suspected in the differential
      diagnosis of three of the cases until results of measles testing were known. The
      diagnosis of SSPE is often not considered by clinicians because of its rarity in
      the United States and the nonspecific clinical manifestations at onset.

PMID- 15505173
TI  - Lower phenytoin serum levels in persons switched from brand to generic phenytoin.
AB  - After generic phenytoin (PHT) was marketed, the authors identified eight adult
      patients (ages 34 to 49) whose seizures increased enough to require intervention
      after switching to generic PHT. The mean total PHT concentration on brand (before
      generic) was 17.7 +/- 5.3 mg/L, decreased to 12.5 +/- 2.7 mg/L with generic, and
      increased to 17.8 +/- 3.9 mg/L after brand was re-introduced. Brand and generic
      PHT do not yield equivalent concentrations in some patients and substitution
      should not be permitted without physician notification.

PMID- 15505174
TI  - The -1021C->T DBH gene variant is not associated with epilepsy or antiepileptic
      drug response.
AB  - Dopamine beta-hydroxylase (DBH) catalyzes the conversion of dopamine to
      norepinephrine (NE). Animal studies show that genes in the NE pathway are
      candidates for susceptibility to epilepsy and antiepileptic drug (AED) response.
      The authors genotyped the -1021C-->T major functional polymorphism in the DBH
      gene in 675 patients with epilepsy and 1,087 controls. The authors found no
      association with epilepsy, several epilepsy subtypes, or AED response. The
      results suggest that the -1021C-->T variant does not contribute to epilepsy.

PMID- 15505175
TI  - Mutations and polymorphisms of the CLCN2 gene in idiopathic epilepsy.
AB  - The authors analyzed the CLCN2 chloride channel gene in 112 probands with
      familial epilepsy, detecting 18 common polymorphisms. Two brothers with
      generalized epilepsy and their asymptomatic father, and a father and son with
      focal epilepsy carried variants of possible functional significance that were not
      found in 192 controls. The authors conclude that CLCN2 mutations may be a rare
      cause of familial epilepsy. Further studies are needed to test if polymorphisms
      in this gene are associated with epilepsy.

PMID- 15505176
TI  - Clinical significance of isolated hippocampal volume asymmetry in childhood
      epilepsy.
AB  - This study defines the clinical characteristics and evolution of 16 epileptic
      children with hippocampal asymmetry (HA) without sclerosis on MRI. The
      association of a positive family history of epilepsy (11/16), low incidence of
      febrile seizures (2/16), and benign prognosis (seizure control in monotherapy in
      11/16, mean follow-up = 4.3 years, range 1 to 10) suggest a different clinical
      presentation than patients with mesial temporal sclerosis. Genetic studies of
      these mostly French Canadian families should help confirm the existence of a
      distinct syndrome.

PMID- 15505177
TI  - Rapid infusion with valproate sodium is well tolerated in patients with epilepsy.
AB  - Many IV antiepileptic drugs administered in emergency situations to patients with
      prolonged seizures have serious adverse effects. For this reason, the authors
      conducted a multicenter, open-label, prospective, dose-escalation study of IV
      valproate sodium administered to patients with epilepsy at rates of infusion of
      up to 6 mg/kg/minute and doses of up to 30 mg/kg. Valproate sodium had no
      clinically significant negative effects on blood pressure and pulse rate and
      caused only mild-to-moderate, reversible adverse events.

PMID- 15505178
TI  - Clinical phenotype of Brazilian families with spinocerebellar ataxia 10.
AB  - Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant ataxia caused by
      an ATTCT repeat expansion in an intron of the SCA10 gene. SCA10 has been reported
      only in Mexican families, in which the disease showed a combination of cerebellar
      ataxia and epilepsy. The authors report 28 SCA10 patients from five new Brazilian
      families. All 28 patients showed cerebellar ataxia without epilepsy, suggesting
      that the phenotypic expression of the SCA10 mutation differs between Brazilian
      and Mexican families.

PMID- 15505180
TI  - Concussion history predicts self-reported symptoms before and following a
      concussive event.
AB  - The authors evaluated how history of concussion affects symptom reporting prior
      to and after sustaining a concussion. At baseline, athletes with a positive
      concussion history reported more current symptomatology than athletes who had
      never been concussed. At 2 hours postinjury, concussed athletes with a history of
      previous concussion (PC) reported fewer symptoms than concussed athletes with no
      previous concussion history (NPC). By 1 week postinjury, however, PC athletes
      reported more symptoms than NPC athletes.

PMID- 15505179
TI  - In vivo evidence of neuronal loss in the hypothalamus of narcoleptic patients.
AB  - A dysfunction of the orexin (hypocretin) system in the hypothalamus has recently
      been linked to the pathogenesis of narcolepsy. The authors used in vivo proton MR
      spectroscopy to assess the N-acetylaspartate (NAA) content in the hypothalamus of
      narcoleptic patients. Hypothalamic NAA/creatine-phosphocreatine was reduced in
      narcoleptic patients compared with control subjects (p < 0.01). Hypothalamic
      neuronal loss/damage is a central pathogenetic feature in narcolepsy.

PMID- 15505181
TI  - Hemodynamic changes in limb shaking TIA associated with anterior cerebral artery
      stenosis.
AB  - Limb shaking TIA is a rare but well-known feature of severe carotid artery
      stenosis. The authors report a patient who developed recurrent shaking movements
      of a leg. An angiogram showed the focal stenosis of the anterior cerebral artery.
      Ictal and postacetazolamide SPECT scans suggested a local hyperfunction of
      cortical neurons and an impaired hemodynamic reserve in the vicinity of the
      ischemic area.

PMID- 15505182
TI  - Hemi-spinal cord infarction due to vertebral artery dissection in congenital
      afibrinogenemia.
AB  - Isolated ischemia of the cervical spinal cord is an uncommon but increasingly
      recognized complication of vertebral artery dissection (VAD). The authors report
      a young patient with congenital afibrinogenemia, who developed VAD with extensive
      unilateral spinal cord infarction, probably caused by local compression of spinal
      radicular feeders at their origin by vertebral artery hematoma.

PMID- 15505183
TI  - Long-term course of L-dopa-responsive dystonia caused by tyrosine hydroxylase
      deficiency.
AB  - The authors report the long-term course of two siblings with L-dopa responsive
      dystonia (DRD) associated with a compound heterozygous mutation in the tyrosine
      hydroxylase (TH) gene. Both siblings manifested with lower-limb onset generalized
      DRD and had a sustained response to low-dose L-dopa therapy for over 35 years.
      Although the l-dopa therapy was delayed up to 20 years after disease onset, there
      were no cognitive or neurologic sequelae of the long-term catecholamine deficit.

PMID- 15505184
TI  - Coincidence of two genetic forms of Charcot-Marie-Tooth disease in a single
      family.
AB  - The authors report a family in which two affected first cousins had a severe
      demyelinating Charcot-Marie-Tooth disease (CMT) phenotype. One had related
      parents, and there were no other affected relatives, suggesting an autosomal
      recessive mode of inheritance. Molecular studies showed that a de novo
      duplication in 17p11.2 and a second mutation in MTMR2 were present.

PMID- 15505185
TI  - Effect of repetitive transcranial magnetic stimulation on rate of memory
      acquisition.
AB  - Repetitive transcranial magnetic stimulation (rTMS) may temporarily accelerate
      knowledge acquisition by neural networks, possibly by promoting rapid Hebbian
      learning. The authors tested this hypothesis in 20 normal subjects by comparing
      the impact of 25 minutes of high-frequency left dorsolateral prefrontal rTMS with
      that of sham rTMS on subsequent knowledge acquisition in several procedural and
      declarative memory domains. No significant group effects, positive or negative,
      were noted for any memory acquisition test, but prefrontal rTMS did reduce motor
      evoked potential threshold.

PMID- 15505186
TI  - Prevalence of hemifacial spasm in Oslo, Norway.
AB  - All patients seeking medical or surgical treatment for hemifacial spasm (HFS) in
      Oslo, Norway were identified in a service-based prevalence study. Only four
      hospital departments offered services for Oslo citizens with HFS. Fifty patients
      with HFS were treated. The total prevalence was 9.8 per 100,000. The prevalence
      increased with age to 39.7 among those older than 70 years. The use of
      antihypertensive drugs was significantly more common in HFS patients (36%) than
      in Oslo's general population.

PMID- 15505187
TI  - Hyperacute post-thrombolysis hematoma by MRI.

PMID- 15505188
TI  - Charcot-Marie-Tooth features and maculopathy in a patient with Danon disease.

PMID- 15505189
TI  - Lack of gastrointestinal symptoms in a 60-year-old patient with MNGIE.

PMID- 15505190
TI  - Ping-pong gaze in coma may not indicate persistent hemispheric damage.

PMID- 15505191
TI  - MRI abnormalities in chronic active varicella zoster infection.

PMID- 15505192
TI  - Delayed response of seizures with vagus nerve stimulation in Lennox-Gastaut
      syndrome.

PMID- 15505193
TI  - Essential tremor course and disability: a clinicopathologic study of 20 cases.

PMID- 15505194
TI  - Effect of levodopa treatment for parkinsonism in welders: a double-blind study.

PMID- 15505195
TI  - Prevalence and clinical characteristics of postictal psychiatric symptoms in
      partial epilepsy.

PMID- 15505196
TI  - Severe worsening of parkinsonism in Lewy body dementia due to donepezil.

PMID- 15505197
TI  - Bright red nuclei.

PMID- 15505198
TI  - State of training in child neurology 1997-2002.

PMID- 15505199
TI  - Expression of antiapoptotic genes bcl-xL and ced-9 in tomato enhances tolerance
      to viral-induced necrosis and abiotic stress.
AB  - D satellite RNA (satRNA) is a strain of cucumber mosaic virus (CMV) satRNA that
      induces an epidemic lethal disease in tomato. No natural resistance or tolerance
      has ever been found. Previously, we demonstrated the involvement of programmed
      cell death in disease development. Here, transgenic tomato plants expressing
      animal antiapoptotic genes bcl-xL and ced-9 were generated through agrobacterium
      mediated transformation. High expression of bcl-xL or ced-9 affected plant growth
      and seed development. Inoculation of seedlings with CMV/D satRNA at T(1) and T(2)
      generations resulted in delayed cell-death symptoms or absence of symptoms. The
      degree of symptom suppression was correlated with increasing expression levels of
      the transgenes. Survival rates were compared among inoculated transgenic lines
      expressing bcl-xL, ced-9, and bcl-xL (G138A), a loss-of-function mutant of bcl
      xL. More than 80% of the bcl-xL and ced-9 T(1) transgenic lines showed higher
      survival rates than the average for bcl-xL (G138A) transgenic lines. Total RNA
      extracted from surviving plants contained D satRNA, indicating systemic
      accumulation of D satRNA. Thus, expression of bcl-xL and ced-9 improved tolerance
      to, rather than resistance to, CMV/D satRNA infection. In addition, expression of
      bcl-xL and ced-9 specifically abrogated the formation of necrotic lesions, but
      not other symptoms, in tomato leaves during chilling at 4 degrees C. At 7 degrees
      C, temperature-induced leaf senescence was dramatically delayed in bcl-xL and ced
      9 transgenic plants, and high levels of anthocyanins accumulated, possibly
      limiting oxidative stress. Hence, expression of these animal antiapoptotic genes
      improved plant survival under abiotic or biotic stress.

PMID- 15505200
TI  - Viruses and the physics of soft condensed matter.

PMID- 15505201
TI  - The unpredictable past of Plasmodium vivax revealed in its genome.

PMID- 15505202
TI  - Nodal protein processing and fibroblast growth factor 4 synergize to maintain a
      trophoblast stem cell microenvironment.
AB  - Before implantation in the uterus, mammalian embryos set aside trophoblast stem
      cells that are maintained in the extraembryonic ectoderm (ExE) during
      gastrulation to generate the fetal portion of the placenta. Their proliferation
      depends on diffusible signals from neighboring cells in the epiblast, including
      fibroblast growth factor 4 (Fgf4). Here, we show that Fgf4 expression is induced
      by the transforming growth factor beta-related protein Nodal. Together with Fgf4,
      Nodal also acts directly on neighboring ExE to sustain a microenvironment that
      inhibits precocious differentiation of trophoblast stem cells. Because the ExE
      itself produces the proteases Furin and PACE4 to activate Nodal, it represents
      the first example, to our knowledge, of a stem cell compartment that actively
      maintains its own microenvironment.

PMID- 15505203
TI  - Variation in sequence and organization of splicing regulatory elements in
      vertebrate genes.
AB  - Although core mechanisms and machinery of premRNA splicing are conserved from
      yeast to human, the details of intron recognition often differ, even between
      closely related organisms. For example, genes from the pufferfish Fugu rubripes
      generally contain one or more introns that are not properly spliced in mouse
      cells. Exploiting available genome sequence data, a battery of sequence analysis
      techniques was used to reach several conclusions about the organization and
      evolution of splicing regulatory elements in vertebrate genes. The classical
      splice site and putative branch site signals are completely conserved across the
      vertebrates studied (human, mouse, pufferfish, and zebrafish), and exonic
      splicing enhancers also appear broadly conserved in vertebrates. However, another
      class of splicing regulatory elements, the intronic splicing enhancers, appears
      to differ substantially between mammals and fish, with G triples (GGG) very
      abundant in mammalian introns but comparatively rare in fish. Conversely, short
      repeats of AC and GT are predicted to function as intronic splicing enhancers in
      fish but are not enriched in mammalian introns. Consistent with this pattern,
      exonic splicing enhancer-binding SR proteins are highly conserved across all
      vertebrates, whereas heterogeneous nuclear ribonucleoproteins, which bind many
      intronic sequences, vary in domain structure and even presence/absence between
      mammals and fish. Exploiting differences in intronic sequence composition, a
      statistical model was developed to predict the splicing phenotype of Fugu introns
      in mammalian systems and was used to engineer the spliceability of a Fugu intron
      in human cells by insertion of specific sequences, thereby rescuing splicing in
      human cells.

PMID- 15505204
TI  - Barrier-limited, microsecond folding of a stable protein measured with hydrogen
      exchange: Implications for downhill folding.
AB  - Folding experiments are conducted to test whether a covalently cross-linked
      coiled-coil folds so quickly that the process is no longer limited by a free
      energy barrier. This protein is very stable and topologically simple, needing
      merely to "zipper up," while having an extrapolated folding rate of k(f) = 2 x
      10(5) s(-1). These properties make it likely to attain the elusive "downhill
      folding" limit, at which a series of intermediates can be characterized. To
      measure the ultra-fast kinetics in the absence of denaturant, we apply NMR and
      hydrogen-exchange methods. The stability and its denaturant dependence for the
      hydrogen bonds in the central part of protein equal the values calculated for
      whole-molecule unfolding. Like-wise, their closing and opening rates indicate
      that these hydrogen bonds are broken and reformed in a single cooperative event
      representing the folding transition from the fully unfolded state to the native
      state. Additionally, closing rates for these hydrogen bonds agree with the
      extrapolated barrier-limited folding rate observed near the melting transition.
      Therefore, even in the absence of denaturant, where DeltaG(eq) approximately -6
      kcal.mol(-1) (1 cal = 4.18 J) and tau(f) approximately 6 mus, folding remains
      cooperative and barrier-limited. Given that this prime candidate for downhill
      folding fails to do so, we propose that protein folding will remain barrier
      limited for proteins that fold cooperatively.

PMID- 15505205
TI  - A beta-oxidation-resistant lipoxin A4 analog treats hapten-induced colitis by
      attenuating inflammation and immune dysfunction.
AB  - Lipoxins and aspirin-triggered 15-epi-lipoxins (ATL) are counter-regulatory
      eicosanoids with potent antiinflammatory actions. Oral efficacy and mechanism of
      action of ZK-192, a beta-oxidation-resistant 3-oxa-ATL analog, were examined in
      trinitrobenzenesulphonate (TNBS)-induced colitis. When dosed orally once daily,
      300 and 1,000 mug/kg ZK-192 markedly attenuated TNBS colitis in rodents both in
      preventive and therapeutic regimens. ZK-192 attenuated weight loss, macroscopic
      and histologic colon injury, mucosal neutrophil infiltration, and colon wall
      thickening. ZK-192 was as effective as 3-10 mg/kg oral prednisolone. ZK-192
      decreased mucosal mRNA levels for several inflammatory mediators: inducible
      nitric oxide synthase, cyclooxygenase 2, and macrophage inflammatory protein 2.
      ZK-192 also decreased mucosal mRNA and protein levels of T helper 1 effector
      cytokines: tumor necrosis factor alpha, IL-2, and IFN-gamma. Systemic levels of
      these cytokines were also dramatically attenuated. CD3/CD28-mediated
      costimulation of T helper 1 effector cytokine release in lamina propria
      mononuclear cells was markedly inhibited by ZK-192 ex vivo and in vitro. ZK-192
      also prevented colitis in lymphocyte-deficient severe combined immunodeficient
      mice, with approximately 75% inhibition of mucosal tumor necrosis factor alpha
      and IL-2 levels. The results are further evidence that innate immune cells
      function as triggers for hapten-induced colitis. The combined antiinflammatory
      and immunomodulatory effects of ZK-192 in TNBS colitis suggest that ATL analogs
      may be an attractive oral treatment approach for inflammatory bowel diseases.

PMID- 15505206
TI  - AtTPK4, an Arabidopsis tandem-pore K+ channel, poised to control the pollen
      membrane voltage in a pH- and Ca2+-dependent manner.
AB  - The Arabidopsis tandem-pore K(+) (TPK) channels displaying four transmembrane
      domains and two pore regions share structural homologies with their animal
      counterparts of the KCNK family. In contrast to the Shaker-like Arabidopsis
      channels (six transmembrane domains/one pore region), the functional properties
      and the biological role of plant TPK channels have not been elucidated yet. Here,
      we show that AtTPK4 (KCO4) localizes to the plasma membrane and is predominantly
      expressed in pollen. AtTPK4 (KCO4) resembles the electrical properties of a
      voltage-independent K(+) channel after expression in Xenopus oocytes and yeast.
      Hyperpolarizing as well as depolarizing membrane voltages elicited instantaneous
      K(+) currents, which were blocked by extracellular calcium and cytoplasmic
      protons. Functional complementation assays using a K(+) transport-deficient yeast
      confirmed the biophysical and pharmacological properties of the AtTPK4 channel.
      The features of AtTPK4 point toward a role in potassium homeostasis and membrane
      voltage control of the growing pollen tube. Thus, AtTPK4 represents a member of
      plant tandem-pore-K(+) channels, resembling the characteristics of its animal
      counterparts as well as plant-specific features with respect to modulation of
      channel activity by acidosis and calcium.

PMID- 15505207
TI  - Effect of torsinA on membrane proteins reveals a loss of function and a dominant
      negative phenotype of the dystonia-associated DeltaE-torsinA mutant.
AB  - Most cases of early-onset torsion dystonia (EOTD) are caused by a deletion of one
      glutamic acid in the carboxyl terminus of a protein named torsinA. The mutation
      causes the protein to aggregate in perinuclear inclusions as opposed to the
      endoplasmic reticulum localization of the wild-type protein. Although there is
      increasing evidence that dysfunction of the dopamine system is implicated in the
      development of EOTD, the biological function of torsinA and its relation to
      dopaminergic neurotransmission has remained unexplored. Here, we show that
      torsinA can regulate the cellular trafficking of the dopamine transporter, as
      well as other polytopic membrane-bound proteins, including G protein-coupled
      receptors, transporters, and ion channels. This effect was prevented by mutating
      the ATP-binding site in torsinA. The dystonia-associated torsinA deletion mutant
      (DeltaE-torsinA) did not have any effect on the cell surface distribution of
      polytopic membrane-associated proteins, suggesting that the mutation linked with
      EOTD results in a loss of function. However, a mutation in the ATP-binding site
      in DeltaE-torsinA reversed the aggregate phenotype associated with the mutant.
      Moreover, the deletion mutant acts as a dominant-negative of wild-type torsinA
      through a mechanism presumably involving association of wild-type and mutant
      torsinA. Taken together, our results provide evidence for a functional role for
      torsinA and a loss of function and a dominant-negative phenotype of the DeltaE
      torsinA mutation. These properties may contribute to the autosomal dominant
      nature of the condition.

PMID- 15505208
TI  - Antigen-independent memory CD8 T cells do not develop during chronic viral
      infection.
AB  - Memory T cells can persist for extended periods in the absence of antigen, and
      long-term T cell immunity is often seen after acute infections. Paradoxically,
      there have been observations suggesting that T cell memory may be antigen
      dependent during chronic infections. To elucidate the underlying mechanisms we
      have compared memory CD8 T cell differentiation during an acute versus chronic
      infection by using the mouse model of infection with lymphocytic choriomeningitis
      virus. We found that during a chronic infection virus-specific CD8 T cells failed
      to acquire the cardinal memory T cell property of long-term antigen-independent
      persistence. These chronically stimulated CD8 T cells were unable to undergo
      homeostatic proliferation, responded poorly to IL-7 and IL-15, and expressed
      reduced levels of the IL-7 and IL-15 receptors, thus providing a possible
      mechanism for the inability of these cells to persist long term in the absence of
      antigen. In striking contrast, virus-specific memory CD8 T cells that developed
      after an acute lymphocytic choriomeningitis virus infection could persist without
      antigen, were capable of self-renewal because of homeostatic proliferation,
      responded efficiently to IL-7 and IL-15, and expressed high levels of receptors
      for these two cytokines. Thus, memory CD8 T cells generated after acute
      infections are likely to have a competitive advantage over CD8 T cells that
      develop during chronic infections. These findings raise concerns about using
      vaccines that may persist and also suggest that there may be limitations and
      challenges in designing effective immunological interventions for the treatment
      of chronic infections and tumors.

PMID- 15505209
TI  - Natural variation in expression of self-incompatibility in Arabidopsis thaliana:
      implications for the evolution of selfing.
AB  - The switch from an out-crossing to a self-fertilizing mating system is one of the
      most prevalent evolutionary trends in plant reproduction and is thought to have
      occurred repeatedly in flowering plants. However, little is known about the
      evolution of self-fertility and the genetic architecture of selfing. Here, we
      establish Arabidopsis thaliana as a model for genetic analysis of the switch to
      self-fertility in the crucifer family, where the ancestral out-crossing mode of
      mating is determined by self-incompatibility (SI), a genetic system controlled by
      the S locus. We show that A. thaliana ecotypes exhibit S-locus polymorphisms and
      differ in their ability to express the SI trait upon transformation with S-locus
      genes derived from the obligate out-crosser Arabidopsis lyrata. Remarkably, at
      least one ecotype was reverted to a stable, self-incompatible phenotype identical
      to that of naturally self-incompatible species. These ecotype differences are
      heritable and reflect the fixation in different A. thaliana populations of
      independent mutations that caused or enforced the switch to self-fertility. Their
      continued analysis promises to identify the loci that were the targets of natural
      selection for selfing and to contribute to a mechanistic understanding of the SI
      response.

PMID- 15505210
TI  - Local modulation of plus-end transport targets herpesvirus entry and egress in
      sensory axons.
AB  - The core structures of many viruses move within cells by association with host
      cytoskeletal motor proteins; however, the mechanisms by which intracellular viral
      particles are transported toward sites of replication or the cell periphery at
      distinct stages of infection remain to be understood. The regulation of
      herpesvirus directional transport in sensory neurons was examined by tracking
      individual viral capsids within axons at multiple frames per s. After entry into
      axons, capsids underwent bidirectional and saltatory movement to the cell body
      independently of endosomes. A comparison of entry transport to a previous
      analysis of capsid axonal transport during egress revealed that capsid targeting
      in and out of cells occurs by modulation of plus-end, but not minus-end, motion.
      Entry transport was unperturbed by the presence of egressing virus from a prior
      infection, indicating that transport direction is not modulated globally by viral
      gene expression, but rather directly by a component of the viral particle.

PMID- 15505211
TI  - EosFP, a fluorescent marker protein with UV-inducible green-to-red fluorescence
      conversion.
AB  - A gene encoding a fluorescent protein from the stony coral Lobophyllia hemprichii
      has been cloned in Escherichia coli and characterized by biochemical and
      biophysical methods. The protein, which we named EosFP, emits strong green
      fluorescence (516 nm) that changes to red (581 nm) upon near-UV irradiation at
      approximately 390 nm because of a photo-induced modification involving a break in
      the peptide backbone next to the chromophore. Single-molecule fluorescence
      spectroscopy shows that the wild type of EosFP is tetrameric, with strong Forster
      resonance coupling among the individual fluorophores. We succeeded in breaking up
      the tetramer into AB and AC subunit dimers by introducing the single point
      mutations V123T and T158H, respectively, and the combination of both mutations
      yielded functional monomers. Fusion constructs with a variety of proteins were
      prepared and expressed in human cells, showing that normal biological functions
      were retained. The possibility to locally change the emission wavelength by
      focused UV light makes EosFP a superb marker for experiments aimed at tracking
      the movements of biomolecules within the living cell.

PMID- 15505212
TI  - Promoter specificity in Pseudomonas aeruginosa quorum sensing revealed by DNA
      binding of purified LasR.
AB  - Along with their cognate acyl-homoserine lactone signals, the quorum sensing
      regulators LasR and RhlR control the expression of hundreds of genes in the
      opportunistic human pathogen Pseudomonas aeruginosa. This extensive, overlapping
      regulatory network affords the opportunity to systematically investigate the
      sequence requirements and specificity determinants of large families of target
      promoters. Many of the P. aeruginosa quorum-controlled genes possess conserved
      palindromic promoter elements predicted to be binding sites for either one or
      both transcriptional regulators, but biochemical proof has not been reported. We
      have purified native LasR and characterized binding to various quorum-controlled
      promoters in vitro. Purified LasR was a dimer in solution that irreversibly bound
      two molecules of 3-oxo-C12-homoserine lactone. LasR bound several las-responsive
      promoters specifically and with high affinity, interacting cooperatively with
      some promoters and noncooperatively with others. LasR recognized some, but not
      all, of the predicted binding sites, and also bound to several unexpected sites.
      In contrast to predictions from genetic data, we found that the recognition
      sequences of las-specific promoters showed little overall sequence conservation
      and did not require dyad symmetry. We found distinct differences in sequence
      composition between las-specific noncooperative, las-specific cooperative, and
      rhl-responsive promoters. These results provide the basis for defining promoter
      specificity elements in P. aeruginosa quorum sensing. Insights into the molecular
      mechanism of LasR function have implications for the development of quorum
      sensing targeted antivirulence compounds.

PMID- 15505213
TI  - Crystal structures of actin-related protein 2/3 complex with bound ATP or ADP.
AB  - Actin-related protein (Arp) 2/3 complex stimulates formation of actin filaments
      at the leading edge of motile cells. Nucleation of filaments depends on
      hydrolysis of ATP bound to Arp2. Here we report crystal structures of Arp2/3
      complex with bound ATP or ADP. The nucleotides are immobilized on the face of
      subdomains 3 and 4 of Arp2, whereas subdomains 1 and 2 are flexible and absent
      from the electron density maps. This flexibility may explain why Arp2 does not
      hydrolyze ATP until the complex is activated. ATP stabilizes a relatively closed
      conformation of Arp3 with the gamma-phosphate bridging loops from opposite sides
      of the cleft. ADP binds Arp3 in a unique conformation that favors an open cleft,
      revealing a conformational change that may occur in actin and Arps when ATP is
      hydrolyzed and phosphate dissociates. These structures provide the an opportunity
      to compare all nucleotide-binding states in an actin-related protein and give
      insights into the function of both the Arp2/3 complex and actin.

PMID- 15505214
TI  - The phytochrome-interacting transcription factor, PIF3, acts early, selectively,
      and positively in light-induced chloroplast development.
AB  - The phytochrome (phy) family of sensory photoreceptors transduce informational
      light signals to selected nuclear genes, inducing plant growth and developmental
      responses appropriate to the environment. Existing data suggest that one
      signaling pathway by which this occurs involves direct, intranuclear interaction
      of the photoactivated phy molecule with PIF3, a basic helix-loop-helix
      transcription factor. Here, we provide evidence from recently identified pif3
      mutant alleles that PIF3 is necessary for early chloroplast greening and rapid
      phy-induced expression of nuclear genes encoding chloroplast components upon
      first exposure of seedlings to light. Therefore, these data indicate that PIF3
      functions to transduce phy signals to genes involved in a critical facet of the
      early seedling deetiolation process, the generation of a functional
      photosynthetic apparatus. When transgenically expressed GUS:PIF3 fusion protein
      constructs were used, we found that PIF3 protein levels are rapidly and
      reversibly modulated by the photoreceptor over diurnal cycles in Arabidopsis
      seedlings. The PIF3 protein declines rapidly to a basal steady-state level upon
      initial light exposure, but reaccumulates to preirradiation levels in darkness
      during the subsequent night period. These data suggest that PIF3 may function in
      early phy signaling at the dark-to-light transition, not only during initial
      seedling deetiolation, but daily at dawn under diurnal light-dark cycles.

PMID- 15505216
TI  - Sole BCR-ABL inhibition is insufficient to eliminate all myeloproliferative
      disorder cell populations.
AB  - Protein kinase inhibitors can be effective in treating selected cancers, but most
      suppress several kinases. Imatinib mesylate has been useful in the treatment of
      Philadelphia chromosome-positive chronic myelogenous leukemia and B cell acute
      lymphoblastic leukemia through the inhibition of BCR-ABL tyrosine kinase
      activity. Imatinib mesylate has also been shown to inhibit KIT, ARG, and platelet
      derived growth factor receptors alpha and beta, and potentially other tyrosine
      kinases. We have produced a mutant allele of BCR-ABL (T315A) that is uniquely
      inhibitable by the small molecule 4-amino-1-tert-butyl-3-(1-naphthyl)pyrazolo[3,4
      d]pyrimidine and used it to demonstrate that sole suppression of BCR-ABL activity
      was insufficient to eliminate BCR-ABL(+) KIT(+)-expressing immature murine
      myeloid leukemic cells. In contrast, imatinib mesylate effectively eliminated BCR
      ABL(+) KIT(+)-expressing leukemic cells. In the cellular context of mature
      myeloid cells and Pro/Pre B cells that do not express KIT, monospecific BCR-ABL
      inhibition was quantitatively as effective as imatinib mesylate in suppressing
      cell growth and inducing apoptosis. These results suggest that the therapeutic
      effectiveness of small molecule drugs such as imatinib mesylate could be due to
      the inhibitor's ability to suppress protein kinases in addition to the dominant
      target.

PMID- 15505217
TI  - Induction in myeloid leukemic cells of genes that are expressed in different
      normal tissues.
AB  - Using DNA microarray and cluster analysis of expressed genes in a cloned line (M1
      t-p53) of myeloid leukemic cells, we have analyzed the expression of genes that
      are preferentially expressed in different normal tissues. Clustering of 547
      highly expressed genes in these leukemic cells showed 38 genes preferentially
      expressed in normal hematopoietic tissues and 122 other genes preferentially
      expressed in different normal nonhematopoietic tissues, including neuronal
      tissues, muscle, liver, and testis. We have also analyzed the genes whose
      expression in the leukemic cells changed after activation of WT p53 and treatment
      with the cytokine IL-6 or the calcium mobilizer thapsigargin. Of 620 such genes
      in the leukemic cells that were differentially expressed in normal tissues,
      clustering showed 80 genes that were preferentially expressed in hematopoietic
      tissues and 132 genes in different normal nonhematopoietic tissues that also
      included neuronal tissues, muscle, liver, and testis. Activation of p53 and
      treatment with IL-6 or thapsigargin induced different changes in the genes
      preferentially expressed in these normal tissues. These myeloid leukemic cells
      thus express genes that are expressed in normal nonhematopoietic tissues, and
      various treatments can reprogram these cells to induce other such
      nonhematopoietic genes. The results indicate that these leukemic cells share with
      normal hematopoietic stem cells the plasticity of differentiation to different
      cell types. It is suggested that this reprogramming to induce in malignant cells
      genes that are expressed in different normal tissues may be of clinical value in
      therapy.

PMID- 15505218
TI  - Epistatic interaction between Arabidopsis FRI and FLC flowering time genes
      generates a latitudinal cline in a life history trait.
AB  - Epistatic gene interactions are believed to be a major factor in the genetic
      architecture of evolutionary diversification. In Arabidopsis thaliana, the FRI
      and FLC genes mechanistically interact to control flowering time, and here we
      show that this epistatic interaction also contributes to a latitudinal cline in
      this life history trait within the species. Two major FLC haplogroups (FLC(A) and
      FLC(B)) are associated with flowering time variation in A. thaliana in field
      conditions, but only in the presence of putatively functional FRI alleles.
      Significant differences in latitudinal distribution of FLC haplogroups in Eurasia
      and North Africa also depend on the FRI genotype. There is significant linkage
      disequilibrium between FRI and FLC despite their location on separate
      chromosomes. Although no nonsynonymous polymorphisms differentiate FLC(A) and
      FLC(B), vernalization induces the expression of an alternatively spliced FLC
      transcript that encodes a variant protein with a radical amino acid replacement
      associated with the two FLC haplogroups. Numerous polymorphisms differentiating
      the FLC haplogroups also occur in intronic regions implicated in the regulation
      of FLC expression. The features of the regulatory gene interaction between FRI
      and FLC in contributing to the latitudinal cline in A. thaliana flowering time
      are consistent with the maintenance of this interaction by epistatic selection.
      These results suggest that developmental genetic pathways and networks provide
      the molecular basis for epistasis, contributing to ecologically important
      phenotypic variation in natural populations and to the process of evolutionary
      diversification.

PMID- 15505219
TI  - Three distinct suppressors of RNA silencing encoded by a 20-kb viral RNA genome.
AB  - Viral infection in both plant and invertebrate hosts requires a virus-encoded
      function to block the RNA silencing antiviral defense. Here, we report the
      identification and characterization of three distinct suppressors of RNA
      silencing encoded by the approximately 20-kb plus-strand RNA genome of citrus
      tristeza virus (CTV). When introduced by genetic crosses into plants carrying a
      silencing transgene, both p20 and p23, but not coat protein (CP), restored
      expression of the transgene. Although none of the CTV proteins prevented DNA
      methylation of the transgene, export of the silencing signal (capable of
      mediating intercellular silencing spread) was detected only from the F(1) plants
      expressing p23 and not from the CP- or p20-expressing F(1) plants, demonstrating
      suppression of intercellular silencing by CP and p20 but not by p23. Thus,
      intracellular and intercellular silencing are each targeted by a CTV protein,
      whereas the third, p20, inhibits silencing at both levels. Notably, CP suppresses
      intercellular silencing without interfering with intracellular silencing. The
      novel property of CP suggests a mechanism distinct to p20 and all of the other
      viral suppressors known to interfere with intercellular silencing and that this
      class of viral suppressors may not be consistently identified by Agrobacterium
      coinfiltration because it also induces RNA silencing against the infiltrated
      suppressor transgene. Our analyses reveal a sophisticated viral counter-defense
      strategy that targets the silencing antiviral pathway at multiple steps and may
      be essential for protecting CTV with such a large RNA genome from antiviral
      silencing in the perennial tree host.

PMID- 15505220
TI  - Self/nonself recognition in ascidian fertilization: vitelline coat protein HrVC70
      is a candidate allorecognition molecule.
AB  - Ascidians are hermaphrodites releasing sperm and eggs simultaneously, but many
      species are self-sterile because of a self/nonself-recognition system in spermegg
      interaction. Here, we show that a 70-kDa vitelline coat protein, HrVC70,
      consisting of 12 epidermal growth factor-like repeats, plays a key role in
      self/nonself recognition during ascidian fertilization. We discovered that the
      amount of HrVC70 of the self-sterile mature oocytes is markedly higher than that
      of the self-fertile immature oocytes and that the selfsterile mature oocytes
      become self-fertile by acid treatment, which is able to release the HrVC70 from
      isolated vitelline coats. In addition, fertilization is strongly inhibited by the
      pretreatment of sperm with HrVC70 from a different individual, but not from the
      same individual, and the number of nonself sperm bound to HrVC70-agarose was
      significantly higher than that of self-sperm. A sequence analysis of HrVC70
      disclosed that several amino acid residues in a restricted region are substituted
      at an individual level, with no identical sequences among the 10 individuals
      tested. Furthermore, genomic DNA analysis revealed that the epidermal growth
      factor-like domains correspond to the exons, and each intron is highly conserved
      among even- and odd-numbered introns, suggesting that multiple gene duplications
      or amplification of this region might have taken place during evolution. It was
      also found that diversity in cDNA sequences is derived from genomic DNA
      polymorphism probably elicited by crossing over and specific nucleotide
      substitutions. These results indicate that HrVC70 is a candidate allogeneic
      recognition molecule in the gamete interaction of the ascidian Halocynthia
      roretzi.

PMID- 15505215
TI  - The gut microbiota as an environmental factor that regulates fat storage.
AB  - New therapeutic targets for noncognitive reductions in energy intake, absorption,
      or storage are crucial given the worldwide epidemic of obesity. The gut microbial
      community (microbiota) is essential for processing dietary polysaccharides. We
      found that conventionalization of adult germ-free (GF) C57BL/6 mice with a normal
      microbiota harvested from the distal intestine (cecum) of conventionally raised
      animals produces a 60% increase in body fat content and insulin resistance within
      14 days despite reduced food intake. Studies of GF and conventionalized mice
      revealed that the microbiota promotes absorption of monosaccharides from the gut
      lumen, with resulting induction of de novo hepatic lipogenesis. Fasting-induced
      adipocyte factor (Fiaf), a member of the angiopoietin-like family of proteins, is
      selectively suppressed in the intestinal epithelium of normal mice by
      conventionalization. Analysis of GF and conventionalized, normal and Fiaf
      knockout mice established that Fiaf is a circulating lipoprotein lipase inhibitor
      and that its suppression is essential for the microbiota-induced deposition of
      triglycerides in adipocytes. Studies of Rag1-/- animals indicate that these host
      responses do not require mature lymphocytes. Our findings suggest that the gut
      microbiota is an important environmental factor that affects energy harvest from
      the diet and energy storage in the host. Data deposition: The sequences reported
      in this paper have been deposited in the GenBank database (accession nos. AY
      667702--AY 668946).

PMID- 15505221
TI  - Facile isolation and the characterization of human retinal stem cells.
AB  - This study identifies and characterizes retinal stem cells (RSCs) in early
      postnatal to seventh-decade human eyes. Different subregions of human eyes were
      dissociated and cultured by using a clonal sphere-forming assay. The stem cells
      were derived only from the pars plicata and pars plana of the retinal ciliary
      margin, at a frequency of approximately 1:500. To test for long-term self
      renewal, both the sphere assay and monolayer passaging were used. By using the
      single sphere passaging assay, primary spheres were dissociated and replated, and
      individual spheres demonstrated 100% self-renewal, with single spheres giving
      rise to one or more new spheres in each subsequent passage. The clonal retinal
      spheres were plated under differentiation conditions to assay the differentiation
      potential of their progeny. The spheres were produced all of the different
      retinal cell types, demonstrating multipotentiality. Therefore, the human eye
      contains a small population of cells (approximately equal to 10,000 cells per
      eye) that have retinal stem-cell characteristics (proliferation, self-renewal,
      and multipotentiality). To test the in vivo potential of the stem cells and their
      progeny, we transplanted dissociated human retinal sphere cells, containing both
      stem cells and progenitors, into the eyes of postnatal day 1 NOD/SCID mice and
      embryonic chick eyes. The progeny of the RSCs were able to survive, migrate,
      integrate, and differentiate into the neural retina, especially as
      photoreceptors. Their facile isolation, integration, and differentiation suggest
      that human RSCs eventually may be valuable in treating human retinal diseases.

PMID- 15505222
TI  - Induction of long-term potentiation and depression is reflected by corresponding
      changes in secretion of endogenous brain-derived neurotrophic factor.
AB  - Neurotrophins play an important role in modulating activity-dependent neuronal
      plasticity. In particular, threshold levels of brain-derived neurotrophic factor
      (BDNF) are required to induce long-term potentiation (LTP) in acute hippocampal
      slices. Conversely, the administration of exogenous BDNF prevents the induction
      of long-term depression (LTD) in the visual cortex. A long-standing missing link
      in the analysis of this modulatory role of BDNF was the determination of the time
      course of endogenous BDNF secretion in the same organotypic preparation in which
      LTP and LTD are elicited. Here, we fulfilled this requirement in slices of
      perirhinal cortex. Classical theta-burst stimulation patterns evoking LTP lasting
      >180 min elicited a large increase in BDNF secretion that persisted 5-12 min
      beyond the stimulation period. Weaker theta-burst stimulation patterns leading
      only to the initial phase of LTP ( approximately 35 min) were accompanied by a
      smaller increase in BDNF secretion lasting <1 min. Sequestration of BDNF by TrkB
      IgG receptor bodies prevented LTP. Low-frequency stimulations leading to LTD were
      accompanied by reductions in BDNF secretion that never lasted beyond the duration
      of the stimulation.

PMID- 15505223
TI  - Integration of reproductive meristem fates by a SEPALLATA-like MADS-box gene.
AB  - Reproductive transition, inflorescence architecture, meristem patterning, and
      floral organ identity have been studied as distinct research areas in plant
      science. By using the ornamental plant Gerbera, we demonstrate that all of these
      keystone aspects of reproductive meristematic fate are integrated genetically by
      a single SEPALLATA-like MADS-box gene from a functional class designated
      previously as "floral homeotic" or "organ identity." This extended regulatory
      network has not been elaborated in the model plant systems, which have a floral
      design and inflorescence-determinacy state that obscures these relationships.

PMID- 15505224
TI  - Growth and hydraulic (not mechanical) constraints govern the scaling of tree
      height and mass.
AB  - The size-dependent variations of plant height L and mass M with respect to basal
      stem diameter D are important to the analysis of a broad range of ecological and
      evolutionary phenomena. Prior examination of some of the world's largest trees
      suggests that the scaling relationships L alpha D(2/3) and M alpha D(8/3) hold
      true, ostensibly as functional adaptations for mechanical stability. This concept
      remains engrained in the literature in the form of null hypotheses (or predictive
      models), despite numerous examples showing that the 2/3 and 8/3 rules are
      violated by small and intermediate-sized plants. Here, we present a growth
      hydraulic model that provides more accurate and biologically realistic
      predictions of L and M. This model also sheds light on why L, D, and M scale
      differently across species and habitats as a result of differences in absolute
      size.

PMID- 15505225
TI  - EncM, a versatile enterocin biosynthetic enzyme involved in Favorskii oxidative
      rearrangement, aldol condensation, and heterocycle-forming reactions.
AB  - The bacteriostatic natural product enterocin from the marine microbe
      "Streptomyces maritimus" has an unprecedented carbon skeleton that is derived
      from an aromatic polyketide biosynthetic pathway. Its caged tricyclic,
      nonaromatic core is derived from a linear poly-beta-ketide precursor that
      formally undergoes a Favorskii-like oxidative rearrangement. In vivo
      characterization of the gene encM through mutagenesis and heterologous
      biosynthesis demonstrated that its protein product not only is solely responsible
      for the oxidative C-C rearrangement, but also facilitates two aldol condensations
      plus two heterocycle forming reactions. In total, at least five chiral centers
      and four rings are generated by this multifaceted flavoprotein. Heterologous
      expression of the enterocin biosynthesis genes encABCDLMN in Streptomyces
      lividans resulted in the formation of the rearranged metabolite desmethyl-5
      deoxyenterocin and the shunt products wailupemycins D-G. Addition of the
      methyltransferase gene encK, which was previously proposed through mutagenesis to
      additionally assist EncM in the Favorskii rearrangement, shifted the production
      to the O-methyl derivative 5-deoxyenterocin. The O-methyltransferase EncK seems
      to be specific for the pyrone ring of enterocin, because bicyclic polyketides
      bearing pyrone rings are not methylated in vivo. Expression of encM with
      different combinations of homologous actinorhodin biosynthesis genes did not
      result in the production of oxidatively rearranged enterocin-actinorhodin hybrid
      compounds as anticipated, suggesting that wild-type EncM may be specific for its
      endogenous type II polyketide synthase or for benzoyl-primed polyketide
      precursors.

PMID- 15505226
TI  - Conformational activation of Ca2+ entry by depolarization of skeletal myotubes.
AB  - Store-operated Ca(2+) entry (SOCE) occurs in diverse cell types in response to
      depletion of Ca(2+) within the endoplasmic/sarcoplasmic reticulum and functions
      both to refill these stores and to shape cytoplasmic Ca(2+) transients. Here we
      report that in addition to conventional SOCE, skeletal myotubes display a
      physiological mechanism that we term excitation-coupled Ca(2+) entry (ECCE). ECCE
      is rapidly initiated by membrane depolarization. Like excitation-contraction
      coupling, ECCE is absent in both dyspedic myotubes that lack the skeletal muscle
      type ryanodine receptor 1 and dysgenic myotubes that lack the dihydropyridine
      receptor (DHPR), and is independent of the DHPR l-type Ca(2+) current. Unlike
      classic SOCE, ECCE does not depend on sarcoplasmic reticulum Ca(2+) release.
      Indeed, ECCE produces a large Ca(2+) entry in response to physiological stimuli
      that do not produce substantial store depletion and depends on interactions among
      three different Ca(2+) channels: the DHPR, ryanodine receptor 1, and a Ca(2+)
      entry channel with properties corresponding to those of store-operated Ca(2+)
      channels. ECCE may provide a fundamental means to rapidly maintain Ca(2+) stores
      and control important aspects of Ca(2+) signaling in both muscle and nonmuscle
      cells.

PMID- 15505227
TI  - Emergence of complex dynamics in a simple model of signaling networks.
AB  - Various physical, social, and biological systems generate complex fluctuations
      with correlations across multiple time scales. In physiologic systems, these long
      range correlations are altered with disease and aging. Such correlated
      fluctuations in living systems have been attributed to the interaction of
      multiple control systems; however, the mechanisms underlying this behavior remain
      unknown. Here, we show that a number of distinct classes of dynamical behaviors,
      including correlated fluctuations characterized by 1/f scaling of their power
      spectra, can emerge in networks of simple signaling units. We found that, under
      general conditions, complex dynamics can be generated by systems fulfilling the
      following two requirements, (i) a "small-world" topology and (ii) the presence of
      noise. Our findings support two notable conclusions. First, complex physiologic
      like signals can be modeled with a minimal set of components; and second, systems
      fulfilling conditions i and ii are robust to some degree of degradation (i.e.,
      they will still be able to generate 1/f dynamics).

PMID- 15505228
TI  - Organization of a primitive memory: olfaction.
AB  - I present a tentative, and schematic, picture of the olfaction storage system in
      early mammalians: (i) how the excitation trains from the olfactory bulb excite
      selectively N types of cells in the piriform cortex and (ii) how these cells
      transfer their information to a storage area. Simple size and connectivity
      requirements impose that each odor is stored in a very small cluster of
      approximately 3 neurons. This surprising result holds even if the model
      parameters are strongly altered (e.g., if N = 10(3) rather than 10(2)).

PMID- 15505230
TI  - Hypochlorous acid and taurine-N-monochloramine in periodontal diseases.
AB  - Chronic periodontitis is a multi-factorial disease involving anaerobic bacteria
      and the generation of an inflammatory response, including the production of
      metalloproteinases, pro-inflammatory cytokines, and eicosanoids. Hypochlorous
      acid (HOCl) and taurine-N-monochloramine (TauCl) are the end-products of the
      neutrophilic polymorphonuclear leukocyte (PMN) respiratory burst. They act
      synergistically to modulate the inflammatory response. In the extracellular
      environment, HOCl and TauCl may directly neutralize interleukin 6 (IL-6) and
      several metalloproteinases, while HOCl increases the capacity of alpha(2)
      macroglobulin to bind Tumor Necrosis Factor-alpha, IL-2, and IL-6, and
      facilitates the release of various growth factors. TauCl inhibits the production
      of inflammatory mediators, prostaglandins, and nitric oxide. HOCl activates
      tyrosine kinase signaling cascades, generating an increase in the production of
      extracellular matrix components, growth factors, and inflammatory mediators.
      Thus, HOCl and TauCl appear to play a crucial role in the periodontal
      inflammatory process. Taken together, these findings may offer opportunities for
      the development of novel host-modulating therapies for the treatment of
      periodontitis.

PMID- 15505229
TI  - Convergence of excitatory and inhibitory hair cell transmitters shapes vestibular
      afferent responses.
AB  - The vestibular semicircular canals respond to angular acceleration that is
      integrated to angular velocity by the biofluid mechanics of the canals and is the
      primary origin of afferent responses encoding velocity. Surprisingly, some
      afferents actually report angular acceleration. Our data indicate that hair
      cell/afferent synapses introduce a mathematical derivative in these afferents
      that partially cancels the biomechanical integration and results in discharge
      rates encoding angular acceleration. We examined the role of convergent synaptic
      inputs from hair cells to this mathematical differentiation. A significant
      reduction in the order of the differentiation was observed for low-frequency
      stimuli after gamma-aminobutyric acid type B receptor antagonist administration.
      Results demonstrate that gamma-aminobutyric acid participates in shaping the
      temporal dynamics of afferent responses.

PMID- 15505231
TI  - The emerging role of the insulin-like growth factors in oral biology.
AB  - The insulin-like growth factors (IGF) are a family of growth factors, receptors
      and binding proteins that are involved in numerous growth and differentiation
      processes, as well as in various pathological conditions. The aim of this review
      is to summarize data that has been accumulating in recent years linking the IGF
      system to a number of physiological and pathological oral processes. The IGF
      system fulfills an important role in growth and development of teeth, mandible,
      maxillae, and tongue. It has been postulated that IGF-I may be of great value in
      the treatment of periodontal defects and in tissue healing. Furthermore, IGF-II
      has been shown to be overexpressed in salivary gland adenomas, suggesting that
      aberrant IGF signaling may be a key factor in the etiology of oral malignancies.
      Understanding the role and regulation of IGF system components in salivary glands
      and other oral structures will be of significant basic and clinical relevance.

PMID- 15505232
TI  - NF-kappaB protection against apoptosis induced by HEMA.
AB  - The cytotoxicity of dental monomers has been widely investigated, but the
      underlying mechanisms have not been elucidated. We studied the molecular
      mechanisms involved in cell death induced by HEMA. In human primary fibroblasts,
      HEMA induced a dose-dependent apoptosis that was confirmed by the activation of
      caspases-8, -9, and -3. We found an increase of reactive oxygen species (ROS) and
      NF-kappaB activation after HEMA exposure. Blocking of ROS production by anti
      oxidants had no direct influence on apoptosis caused by HEMA, but inhibition of
      NF-kappaB increased the fraction of apoptotic cells. Accordingly, mouse embryonic
      fibroblasts (MEF) from p65-/- mice were more susceptible to HEMA-induced
      apoptosis than were wild-type controls. Our results indicate that exposure to
      HEMA triggers apoptosis and that this mechanism is not directly dependent upon
      redox signaling. Nevertheless, ROS induction by HEMA activates NF-kappaB, which
      exerts a protective role in counteracting apoptosis.

PMID- 15505233
TI  - Fluid movement across the resin-dentin interface during and after bonding.
AB  - This study evaluated the extent of water penetration through resin-dentin
      interfaces before and after being sealed with adhesives. Four adhesive resin
      systems (2 total-etch adhesives and 2 self-etching primer adhesives) were used in
      this study. Dentin disks were placed in a split-chamber device, and in situ fluid
      movement across dentin was measured, with and without physiological pressure,
      during bonding procedures or 24 hrs after bonding. The fluid movement across
      dentin occurs via dentin tubules after acid-etching. Large outward or inward
      fluid shifts across dentin were observed during air-drying and light-curing for
      resin application. The amount of fluid movement across resin-bonded dentin when
      total-etch adhesives were used was significantly greater than that with self
      etching adhesives. The milder acid-etching effects of self-etching primers may
      retain hybridized smear plugs within the tubules that reduce outward fluid flow,
      resulting in superior dentin sealing.

PMID- 15505234
TI  - Effect of dentinal fluid composition on dentin demineralization in vitro.
AB  - Dentin demineralization is reduced by perfusion with water. We hypothesized that
      a simulated dentinal fluid (SDF) that contains albumin, in addition to
      electrolytes, would be more effective in reducing dentin demineralization than
      water alone, and this effect would increase with increasing flow rate of SDF.
      Perfusion rate in tooth segments that carried buccal cervical dentin windows was
      measured in a fluid transport set-up. These windows were then demineralized under
      perfusion with water, or SDF at 1.47 kPa for 31 days. We analyzed integrated
      mineral loss and lesion depth with the use of transverse microradiography (TMR),
      which revealed that 38% more mineral dissolved from dentin lesions perfused with
      water than from those perfused with SDF. The former were also 18% deeper. Flow
      rate of dentinal fluid showed no correlation with demineralization. We concluded
      that composition of dentinal fluid is an important determinant of the rate of
      lesion formation and progression in dentin.

PMID- 15505235
TI  - The timing of subsequent treatment for teeth restored with large amalgams and
      crowns: factors related to the need for subsequent treatment.
AB  - Crowns and large amalgams protect structurally compromised teeth to various
      degrees in different situations. The aim of this investigation was to evaluate
      the survival of teeth with these two types of restorations and the factors
      associated with better outcomes. Retrospective administrative and chart data were
      used. Survival was defined and modeled as: (1) receipt of no treatment and (2)
      receipt of no catastrophic treatment over five- and 10-year periods. Analyses
      included: Kaplan-Meier survival curves, Log-Rank tests, and Cox proportional
      hazards regression modeling. Crowns survived longer with no treatment and with no
      catastrophic treatment; however, mandibular large amalgams were least likely to
      have survived with no treatment, and maxillary large amalgams were least likely
      to have survived with no catastrophic treatment. Having no adjacent teeth also
      decreased survival. Crowns survived longer than large amalgams, but factors such
      as arch type and the presence of adjacent teeth contributed to the survival of
      large amalgams.

PMID- 15505236
TI  - A comprehensive index for the modeling of smoking history in periodontal
      research.
AB  - Cigarette smoking is both a strong and common risk factor for chronic
      periodontitis. It is a multi-dimensional exposure that is difficult to model
      accurately. We propose a new comprehensive smoking index (CSI) that accounts for
      intensity, duration, and recency of smoking and allows for estimation of the half
      life of the smoking effect. Using NHANES III data from 12,623 subjects aged 20+
      yrs, we compared the performance of the CSI with that of various conventional
      approaches using multiple logistic regression models of chronic periodontitis.
      The estimate of the smoking effect's half-life was 1.5 yrs (95% CI, 0.5-2.5 yrs).
      Use of the new index resulted in best model fit and the highest Wald statistic
      for the smoking effect on chronic periodontitis. The results suggest that use of
      the CSI may be a more comprehensive, efficient, and parsimonious approach to the
      modeling of smoking history in periodontal research.

PMID- 15505237
TI  - Head movements during chewing: relation to size and texture of bolus.
AB  - Coordinated mandibular and head-neck movements during jaw opening-closing
      activities suggest a close functional linkage between the jaw and the neck
      regions. The present study investigated whether size and texture of bolus can
      influence head-neck behavior during chewing. Using an optoelectronic 3-D
      recording technique, we analyzed concomitant mandibular and head-neck movements
      in 12 healthy adults chewing small (3 g) and large (9 g) boluses of chewing gum
      and Optosil. The main finding was a head extension during chewing, the amount of
      which was related mainly to bolus size. Furthermore, each chewing cycle was
      accompanied not only by mandibular movements, but also by head extension-flexion
      movements. Larger head movement amplitudes were correlated with larger size and,
      to some extent, also with harder texture of the bolus. The results suggest that
      head-neck behavior during chewing is modulated in response to changes in jaw
      sensory-motor input.

PMID- 15505238
TI  - Dental caries in HIV-seropositive women.
AB  - Reports that compare dental caries indices in HIV-seropositive (HIV+) subjects
      with HIV-seronegative (HIV-) subjects are rare. The objective of this study was
      to determine if there was an association between HIV infection and dental caries
      among women enrolled in the Women's Interagency HIV Study. Subjects included 538
      HIV+ and 141 HIV- women at baseline and 242 HIV+ and 66 HIV- women at year 5.
      Caries indices included DMFS and DFS (coronal caries) and DFSrc (root caries).
      Cross-sectional analysis of coronal caries data revealed a 1.2-fold-higher caries
      prevalence among HIV+ women compared with HIV- women. Longitudinally, DMFS
      increased with increasing age and lower average stimulated salivary volume. Root
      caries results were not significant except for an overall increased DFSrc
      associated with smoking. Anti-retroviral therapy was not identified as a risk
      factor for dental caries.

PMID- 15505239
TI  - Synergistic effects of streptococcal glucosyltransferases on adhesive biofilm
      formation.
AB  - Glucosyltransferases (GTF)-I and GTF-SI of Streptococcus mutans synthesize water
      insoluble and both water-soluble and -insoluble glucans, respectively, and play
      essential roles in the sucrose-dependent adhesion of the organism to tooth
      surfaces. To examine the interactions of different GTFs on artificial biofilm
      formed by S. mutans and other oral streptococci, we generated GTF-I- and GTF-SI
      hyperproducing isogenic mutant strains. Transformant B42-21, which hyperexpressed
      GTF-SI, exhibited firm adhesion in the presence of sucrose, whereas transformant
      B42-10, which hyperexpressed GTF-I, failed to exhibit firm adhesion. Furthermore,
      co-culture of transformant B42-21 with water-soluble glucan-synthesizing
      Streptococcus sanguinis yielded firm adhesion, while the addition of dextran T10
      to B42-21 growing culture had no effect on adhesion. These findings suggest that
      GTF-SI has a strong effect on sucrose-dependent adhesion and is essential for
      biofilm formation on smooth surfaces, in cooperation with water-soluble glucans
      synthesized de novo by oral streptococci that inherently lack cell adhesion
      ability.

PMID- 15505240
TI  - Chondroitin sulfate in palatal wound healing.
AB  - Chondroitin sulfate is up-regulated in granulation tissue during wound healing.
      To investigate the role of chondroitin sulfate in the wound-healing process after
      surgical repair of cleft palate, we isolated and cultured rabbit palatal
      fibroblasts. Treatment with chondroitin-6-sulfate resulted in a dose-dependent
      increase in cell adhesion and cell proliferation, whereas the reverse effects
      were seen after chondroitinase degradation of chondroitin sulfate. The biological
      actions of chondroitin sulfate appeared to be dependent on the presence and
      position of sulfate groups. Inhibition of glycosaminoglycan sulfation by chlorate
      treatment led to reduced cell adhesion and cell proliferation and a slower rate
      of wound closure in vitro. Furthermore, exposure to chondroitin-4-sulfate
      resulted in a dose-dependent reduction in cell adhesion. Together, these results
      show that chondroitin sulfate is involved in palatal wound healing.

PMID- 15505241
TI  - Carrots and sticks for quality health care.

PMID- 15505243
TI  - Social and economic justice: the road to health.

PMID- 15505245
TI  - Seeking clarification of osteoporosis guidelines.

PMID- 15505246
TI  - Seeking clarification of osteoporosis guidelines.

PMID- 15505248
TI  - Mapping malaria.

PMID- 15505249
TI  - How children see themselves.

PMID- 15505251
TI  - To self-cite or not to self-cite.

PMID- 15505253
TI  - Rofecoxib (Vioxx) voluntarily withdrawn from market.

PMID- 15505254
TI  - Lack of Aboriginal health professionals a "huge issue".

PMID- 15505255
TI  - Massive aid mobilization needed in Darfur: MSF.

PMID- 15505256
TI  - Canada achieves lowest perinatal mortality ever.

PMID- 15505258
TI  - Manitoba to fast-track less critical emergency patients.

PMID- 15505259
TI  - 10-million dollars malpractice award largest ever.

PMID- 15505260
TI  - Tilting at windmills: health reform and the 2004 US presidential election.

PMID- 15505261
TI  - Implantable cardioverter defibrillators: therapy against Canada's leading killer.

PMID- 15505262
TI  - Applying the new STEMI guidelines: 1. Reperfusion in acute ST-segment elevation
      myocardial infarction.

PMID- 15505263
TI  - Applying the new STEMI guidelines: 2. Disturbances of cardiac rhythm after ST
      segment elevation myocardial infarction.

PMID- 15505264
TI  - Infliximab and serious hematologic events.

PMID- 15505265
TI  - An unusual structure near the porta hepatis: what's your diagnosis?

PMID- 15505266
TI  - Preventing cold chain failure: vaccine storage and handling.

PMID- 15505267
TI  - Use of implantable cardioverter defibrillators after out-of-hospital cardiac
      arrest: a prospective follow-up study.
AB  - BACKGROUND: Survivors of out-of-hospital cardiac arrest are at high risk of
      recurrent arrests, many of which could be prevented with implantable cardioverter
      defibrillators (ICDs). We sought to determine the ICD insertion rate among
      survivors of out-of-hospital cardiac arrest and to determine factors associated
      with ICD implantation. METHODS: The Ontario Prehospital Advanced Life Support
      (OPALS) study is a prospective, multiphase, before-after study assessing the
      effectiveness of prehospital interventions for people experiencing cardiac
      arrest, trauma or respiratory arrest in 19 Ontario communities. We linked OPALS
      data describing survivors of cardiac arrest with data from all defibrillator
      implantation centres in Ontario. RESULTS: From January 1997 to April 2002, 454
      patients in the OPALS study survived to hospital discharge after experiencing an
      out-of-hospital cardiac arrest. The mean age was 65 (standard deviation 14)
      years, 122 (26.9%) were women, 398 (87.7%) had a witnessed arrest, 372 (81.9%)
      had an initial rhythm of ventricular tachycardia or ventricular fibrillation
      (VT/VF), and 76 (16.7%) had asystole or another arrhythmia. The median cerebral
      performance category at discharge (range 1-5, 1 = normal) was 1. Only 58 (12.8%)
      of the 454 patients received an ICD. Patients with an initial rhythm of VT/VF
      were more likely than those with an initial rhythm of asystole or another rhythm
      to undergo device insertion (adjusted odds ratio [OR] 9.63, 95% confidence
      interval [CI] 1.31-71.50). Similarly, patients with a normal cerebral performance
      score were more likely than those with abnormal scores to undergo ICD insertion
      (adjusted OR 12.52, 95% CI 1.74-92.12). INTERPRETATION: A minority of patients
      who survived cardiac arrest underwent ICD insertion. It is unclear whether this
      low usage rate reflects referral bias, selection bias by electrophysiologists,
      supply constraint or patient preference.

PMID- 15505268
TI  - Effect of periodic letters on evidence-based drug therapy on prescribing
      behaviour: a randomized trial.
AB  - BACKGROUND: The effect of regular and expected printed educational materials on
      physician prescribing behaviour has not been studied. We sought to measure the
      impact of a series of evidence-based drug therapy letters mailed to physicians in
      British Columbia on prescribing to newly treated patients. METHODS: A paired,
      cluster randomized community design was used. The study population included 499
      physicians from 24 local health areas in British Columbia. Local health areas
      were paired by number of physicians, and 1 of each pair was randomly selected and
      its physicians assigned to an intervention group or a control group. The
      intervention was 12 issues of an evidence-based series called Therapeutics
      Letter. Physicians in the control group (n = 241) received the letters 3-8 months
      after physicians in the intervention group (n = 258). The impact on prescribing
      to newly treated patients (defined as patients who had not previously made a
      claim for any medication from the class of drugs profiled in the letter) was
      analyzed using the drug claims database of BC Pharmacare, a publicly funded drug
      benefits program that covered all seniors and people receiving social assistance.
      RESULTS: The probability of prescribing a drug recommended in the Therapeutics
      Letter rather than another drug in the same class increased by 30% in the 3
      months after the mailing of the letter relative to the preceding 3 months,
      adjusted for any before-after changes in the control group (relative risk 1.30;
      95% confidence interval 1.13-1.52). No letter achieved statistical significance
      on its own. However, 11 of the 12 letters produced prescribing changes in the
      predicted direction such that the overall result was significant when their
      effect was combined. INTERPRETATION: The combined effect of an ongoing series of
      printed letters distributed from a credible and trusted source can have a
      clinically significant effect on prescribing to newly treated patients.

PMID- 15505269
TI  - Cutaneous nocardiosis complicating management of Crohn's disease with infliximab
      and prednisone.
AB  - Infliximab is a chimeric anti-tumour necrosis factor-alpha antibody that is
      efficacious in treating Crohn's disease. However, its immunomodulatory properties
      increase susceptibility to opportunistic infections. We present a case of
      cutaneous Nocardia infection in a patient who was taking infliximab for Crohn's
      disease. The case illustrates the challenges in the diagnosis and management of
      this disease and serves as a reminder of the complications associated with the
      use of immunomodulatory agents.

PMID- 15505270
TI  - The impact of new guidelines for glucose tolerance testing on clinical practice
      and laboratory services.

PMID- 15505271
TI  - Canada's programs to prevent mental health problems in children: the research
      practice gap.

PMID- 15505272
TI  - Adrenomyeloneuropathy as a cause of primary adrenal insufficiency and spastic
      paraparesis.
AB  - Adrenomyeloneuropathy is a varient of adrenoleukodystrophy, both of which are
      rare inherited disorders of peroxisomes characterized by the accumulation of very
      long-chain fatty acids in plasma, the central and peripheral nervous systems,
      adrenal glands and testes, which leads to dysfunction of these organs and
      systems. In this article, we describe an illustrative case of
      adrenomyeloneuropathy and discuss the clinical presentation, diagnosis and
      management of the 2 disorders.

PMID- 15505273
TI  - Profiling the perpetrator.

PMID- 15505274
TI  - Adjuvant chemotherapy for elderly women with hormone receptor-positive breast
      cancer: an old(er) problem.

PMID- 15505275
TI  - Gene expression signature with independent prognostic significance in epithelial
      ovarian cancer.
AB  - PURPOSE: Currently available clinical and molecular prognostic factors provide an
      imperfect assessment of prognosis for patients with epithelial ovarian cancer
      (EOC). In this study, we investigated whether tumor transcription profiling could
      be used as a prognostic tool in this disease. METHODS: Tumor tissue from 68
      patients was profiled with oligonucleotide microarrays. Samples were randomly
      split into training and validation sets. A three-step training procedure was used
      to discover a statistically significant Kaplan-Meier split in the training set.
      The resultant prognostic signature was then tested on an independent validation
      set for confirmation. RESULTS: In the training set, a 115-gene signature referred
      to as the Ovarian Cancer Prognostic Profile (OCPP) was identified. When applied
      to the validation set, the OCPP distinguished between patients with unfavorable
      and favorable overall survival (median, 30 months v not yet reached,
      respectively; log-rank P = .004). The signature maintained independent prognostic
      value in multivariate analysis, controlling for other known prognostic factors
      such as age, stage, grade, and debulking status. The hazard ratio for death in
      the unfavorable OCPP group was 4.8 (P = .021 by Cox proportional hazards
      analysis). CONCLUSION: The OCPP is an independent prognostic determinant of
      outcome in EOC. The use of gene profiling may ultimately permit identification of
      EOC patients appropriate for investigational treatment approaches, based on a low
      likelihood of achieving prolonged survival with standard first-line platinum
      based therapy.

PMID- 15505276
TI  - Disease-free survival advantage of weekly epirubicin plus tamoxifen versus
      tamoxifen alone as adjuvant treatment of operable, node-positive, elderly breast
      cancer patients: 6-year follow-up results of the French adjuvant study group 08
      trial.
AB  - PURPOSE: To assess whether an epirubicin (EPI) -based chemotherapy plus hormonal
      regimen improves disease-free (DFS) in women older than 65 years, with node
      positive, operable breast cancer (BC), relative to tamoxifen (TAM) alone.
      PATIENTS AND METHODS: A total of 338 patients were randomly assigned after
      surgery to receive TAM 30 mg/d for 3 years (TAM, n = 164), or EPI 30 mg on days
      1, 8, and 15 every 28 days for six cycles plus TAM 30 mg/d for 3 years (EPI-TAM,
      n = 174). In both arms, patients received radiotherapy, delivered after
      chemotherapy (CT) in the EPI-TAM group. RESULTS: The 6-year DFS rates were 69.3%
      with TAM and 72.6% with EPI-TAM (P = .14). The multivariate analysis shows a
      relative risk of relapse of 1.93 (95% CI, 1.70 to 2.17) with TAM compared with
      EPI-TAM (P = .005). The 6-year OS, related to disease progression, was 79.1% and
      79.8%, respectively (P = .41). Compliance with CT was good: 96.9% of patients
      received six cycles. The acute toxicity per patient was mild: grade 2 neutropenia
      in 5.9%, grade 2 anemia in 2.0%, grade 3 nausea or vomiting in 4.6%, and grade 3
      alopecia in 7.2%. Five cases (in five patients) of decreased left ventricular
      ejection fraction occurred after CT: three after adjuvant CT, and two after
      anthracycline-based CT for relapse. One patient died as a result of dysrhythmia
      related to carcinomatous lymphangitis. No secondary leukemia occurred.
      CONCLUSION: This study conducted in node-positive elderly patients demonstrates a
      significant contribution of a weekly EPI regimen in terms of DFS. Moreover, this
      regimen is safe for hematologic, nonhematologic, and cardiac toxicities.

PMID- 15505277
TI  - Types of procedures performed by diagnostic radiology practices: past patterns
      and future directions.
AB  - OBJECTIVE: The purpose of our study was to determine the types of imaging
      procedures performed by diagnostic radiology practices and the patterns and
      differences related to practice characteristics. MATERIALS AND METHODS: The
      American College of Radiology (ACR) surveyed 970 practices by mail, using a 65
      item questionnaire, in 1999. A response rate of 66% was achieved. Weighting was
      used to make responses representative of all radiology practices in the United
      States. Trends were explored by making comparisons with data from a 1991-1992 ACR
      study. RESULTS: Among the types of procedures studied, the highest percentage of
      multiradiologist diagnostic-radiology-only practices performed mammography (95%)
      and sonography (94%). (General conventional radiography and fluoroscopy were not
      studied.) The lowest percentage of these practices performed interventional
      procedures (69%) and MRI (77%). Solo practices showed less diversity in types of
      procedures performed than did multiradiologist practices and were a good deal
      less likely to perform each type of procedure except mammography and sonography.
      Generally, higher percentages of practices in nonmetropolitan cities or towns and
      rural practices performed various types of procedures than practices in
      metropolitan areas. Practice size, types of settings served (hospital or
      nonhospital), and practice type also influenced the number of types of procedures
      performed by a practice. The fraction of practices performing CT decreased from
      91% to 83% between 1991-1992 and 1999. Percentages for other types of procedures
      were generally stable over time. CONCLUSION: Certain practice characteristics
      play a role in determining the types of imaging procedures a diagnostic radiology
      practice performs. The decline in the percentage of practices providing CT and
      the failure during the 1990s of percentages for MRI and interventional radiology
      to increase from a relatively low base is worrisome. Future analyses based on a
      subsequent ACR survey will provide further insights into trends.

PMID- 15505278
TI  - Observational studies in radiology.

PMID- 15505279
TI  - Radiologists' performance for differentiating benign from malignant lung nodules
      on high-resolution CT using computer-estimated likelihood of malignancy.
AB  - OBJECTIVE: The purpose of our study was to evaluate whether a computer-aided
      diagnosis (CAD) scheme can assist radiologists in distinguishing small benign
      from malignant lung nodules on high-resolution CT (HRCT). MATERIALS AND METHODS:
      We developed an automated computerized scheme for determining the likelihood of
      malignancy of lung nodules on multiple HRCT slices; the likelihood estimate was
      obtained from various objective features of the nodules using linear discriminant
      analysis. The data set used in this observer study consisted of 28 primary lung
      cancers (6-20 mm) and 28 benign nodules. Cancer cases included nodules with pure
      ground-glass opacity, mixed ground-glass opacity, and solid opacity. Benign
      nodules were selected by matching their size and pattern to the malignant
      nodules. Consecutive region-of-interest images for each nodule on HRCT were
      displayed for interpretation in stacked mode on a cathode ray tube monitor. The
      images were presented to 16 radiologists-first without and then with the computer
      output-who were asked to indicate their confidence level regarding the malignancy
      of a nodule. Performance was evaluated by receiver operating characteristic (ROC)
      analysis. RESULTS: The area under the ROC curve (Az value) of the CAD scheme
      alone was 0.831 for distinguishing benign from malignant nodules. The average Az
      value for radiologists was improved with the aid of the CAD scheme from 0.785 to
      0.853 by a statistically significant level (p = 0.016). The radiologists'
      diagnostic performance with the CAD scheme was more accurate than that of the CAD
      scheme alone (p < 0.05) and also that of radiologists alone. CONCLUSION: CAD has
      the potential to improve radiologists' diagnostic accuracy in distinguishing
      small benign nodules from malignant ones on HRCT.

PMID- 15505280
TI  - Volumetric assessment of pulmonary nodules with ECG-gated MDCT.
AB  - OBJECTIVE: The objective of our study was to assess physiologic lung deformation
      and compression originating from cardiovascular motion and their subsequent
      impact on determining the volume of small pulmonary nodules throughout the
      cardiac cycle on ECG-gated MDCT. SUBJECTS AND METHODS: Seventy-three small
      noncalcified pulmonary nodules were identified in 30 patients who underwent ECG
      gated MDCT. The volume of each nodule was assessed throughout the cardiac cycle
      using computer-aided automatic segmentation algorithms, and the assessment was
      repeated three times. To ensure the validity of the subtle changes in volume that
      were detected, we determined the volume and signal attenuation in phantom data
      sets and patient nodules without temporal or spatial differentiation.
      Subsequently, nodules were assigned to pulmonary segments, and volume changes
      were correlated to cardiac phases, nodular location, and mean nodular size.
      Statistical multivariate tests were performed to evaluate significant patterns.
      RESULTS: The validity of significant measurements was proven in evaluated phantom
      data sets with a general tendency toward overestimating nodular volume (p =
      0.492). Statistical evaluation of nodular signal attenuation confirmed true
      deformation and compression of nodules rather than partial volume effects as the
      reason for volume variations (p = 0.874). Differentiating pulmonary nodules in
      cardiac phases, pulmonary locations, and mean nodular volumes, we found that one
      single effect did not determine the amount of cardiovascular motion conveyed to
      pulmonary parenchyma and subsequently led to nodule deformation. Multivariate
      testing revealed statistically significant measures identifying patterns
      correlating variation in nodular volume with cardiac phase (p < 0.001), nodular
      location (p = 0.007), and mean nodular size (p < 0.001). CONCLUSION:
      Cardiovascular motion was disproportionately conveyed to various pulmonary
      segments and led to changes in the volume of pulmonary nodules, especially in
      small pulmonary nodules. A precise volumetric assessment was therefore possible
      only by identifying the underlying cardiac phase.

PMID- 15505281
TI  - Invasive aspergillosis of the mediastinum and left hilum: CT features.

PMID- 15505283
TI  - Digital radiography with dual-energy subtraction: improved evaluation of cardiac
      calcification.
AB  - OBJECTIVE: The objective of our study was to describe cardiac applications for
      digital radiography with dual-energy subtraction. CONCLUSION: Dual-energy
      subtraction digital radiography offers potentially important new information in
      the assessment of coronary artery disease.

PMID- 15505284
TI  - CT of a ruptured vein graft pseudoaneurysm: an unusual cause of superior vena
      cava obstruction.

PMID- 15505282
TI  - Clinical relevance of retrograde inferior vena cava or hepatic vein opacification
      during contrast-enhanced CT.
AB  - OBJECTIVE: The purpose of this investigation was to explore the clinical
      relevance of retrograde inferior vena cava or hepatic vein opacification during
      contrast-enhanced CT. MATERIALS AND METHODS: We retrospectively identified 127
      patients who underwent contemporaneous contrast-enhanced CT of the chest or
      abdomen and echocardiography. On CT, the presence of retrograde inferior vena
      cava or hepatic vein opacification and the rate of IV contrast injection (> 3
      mL/sec, high; < or = 3 mL/sec, low) were recorded. On echocardiography, the
      presence of tricuspid regurgitation, pulmonary hypertension, or right ventricular
      systolic dysfunction was recorded. RESULTS: Retrograde inferior vena cava or
      hepatic vein opacification was more common in studies performed with a high
      rather than a low contrast injection rate (28/56 vs 6/71 patients, respectively;
      p < 0.01). This finding was 31% sensitive (5/16) and 98% specific (54/55) for
      right-sided heart disease at low contrast injection rates, and 81% sensitive
      (17/21) and 69% specific (24/35) at high injection rates. Multivariate logistic
      regression models showed that high injection rate, tricuspid regurgitation,
      pulmonary hypertension, and right ventricular systolic dysfunction were
      independent predictors of retrograde inferior vena cava or hepatic vein
      opacification (p < 0.05 for each). CONCLUSION: Retrograde opacification of the
      inferior vena cava or hepatic veins on CT is a specific but insensitive sign of
      right-sided heart disease at low contrast injection rates, but the usefulness of
      this classic sign decreases with high injection rates. This realization is
      important because many centers increasingly use high-injection-rate CT.

PMID- 15505285
TI  - MDCT of anomalous unilateral single pulmonary vein.

PMID- 15505286
TI  - Paradoxical embolism detected on CT angiography and treated with temporary
      inferior vena cava filtration and anticoagulation.

PMID- 15505287
TI  - Distinction between cerebral abscesses and high-grade neoplasms by dynamic
      susceptibility contrast perfusion MRI.
AB  - OBJECTIVE: The purpose of the study was to determine whether dynamic
      susceptibility contrast perfusion MRI allowed distinction of cerebral abscesses
      from cystic high-grade brain neoplasms. CONCLUSION: In this small preliminary
      study, dynamic susceptibility perfusion MRI allowed distinction of cerebral
      abscesses from rim-enhancing high-grade gliomas. Validation of these results
      using a prospective large study is warranted.

PMID- 15505288
TI  - Imaging of thoracoabdominal involvement in Erdheim-Chester disease.

PMID- 15505289
TI  - A modified CT severity index for evaluating acute pancreatitis: improved
      correlation with patient outcome.
AB  - OBJECTIVE: This study was conducted to assess the correlation with patient
      outcome and interobserver variability of a modified CT severity index in the
      evaluation of patients with acute pancreatitis compared with the currently
      accepted CT severity index. MATERIALS AND METHODS: Of 266 consecutive patients
      diagnosed with acute pancreatitis during a 1-year period, 66 underwent contrast
      enhanced MDCT within 1 week of the onset of symptoms. Three radiologists who were
      blinded to patient outcome independently scored the severity of the pancreatitis
      using both the currently accepted and modified CT severity indexes. The modified
      index included a simplified assessment of pancreatic inflammation and necrosis as
      well as an assessment of extrapancreatic complications. Outcome parameters
      included the length of hospital stay; the need for surgery or percutaneous
      intervention; and the occurrences of infection, organ failure, and death. For
      both the current and modified indexes, correlation between the severity of the
      pancreatitis and patient outcome was estimated using the Wilcoxon's rank sum test
      and Fisher's exact test. Interobserver agreement for both indexes was calculated
      using the kappa statistic. RESULTS: When applying the modified index, the
      severity of pancreatitis and the following parameters correlated more closely
      than when the currently accepted index was applied: the length of the hospital
      stay (0-34 days) (modified index [p = 0.0054-0.0714] vs current index [p = 0.0052
      0.3008]); the need for surgical or percutaneous procedures (10/66 patients)
      (modified index [p = 0.0112] vs current index [p = 0.0324]); and the occurrence
      of infection (21/66 patients) (modified index [p < 1e(-10)] vs current index [p <
      1e(-04)]). Significant correlation between the severity of pancreatitis and the
      development of organ failure (9/66 patients) was seen only using the modified
      index (p = 0.0024), not the current index (p = 0.0513). The interobserver
      agreement was similar with the modified (kappa range, 0.71-0.85) and the current
      (kappa range, 0.63-0.86) indexes. CONCLUSION: The modified CT severity index
      correlates more closely with patient outcome measures than the currently accepted
      CT severity index, with similar interobserver variability.

PMID- 15505290
TI  - Pancreatic duct after pancreatoduodenectomy: morphologic and functional
      evaluation with secretin-stimulated MR pancreatography.
AB  - OBJECTIVE: The purpose of this study was to evaluate the usefulness of secretin
      enhanced MR pancreatography in evaluating morphologic changes and pancreatic
      function after pancreatoduodenectomy. SUBJECTS AND METHODS: Twenty patients who
      underwent pancreatoduodenectomy were evaluated with secretin MR pancreatography.
      Single-shot fast spin-echo T2-weighted dynamic MR pancreatograms were obtained
      before and every minute for 10 min after secretin injection. Image analysis
      included image quality for the visualization of the pancreatic duct and
      morphologic features of the pancreatic duct (side branches, ductal narrowing,
      irregular ductal contour, and patency of the anastomotic site). Pancreatic
      function was assessed using the Van de Kamer method and the fasting blood glucose
      and oral glucose tolerance tests. Jejunal filling was graded from the lowest
      amount of filling (grade 1) to normal filling (grade 3) on the last MR
      pancreatogram. RESULTS: The visualization of the main pancreatic duct was
      significantly improved with dynamic MR pancreatography (p < 0.05). The
      anastomotic site was visualized in 14 patients (70%) on MR pancreatography after
      secretin administration (p < 0.05). No statistically significant improvement in
      other morphologic data was seen after secretin administration. The sensitivity,
      specificity, positive predictive value, and negative predictive value of reduced
      jejunal filling (grade 1) for assessment of reduced pancreatic exocrine function
      were 92%, 71%, 85%, and 83%, respectively. The relation between reduced jejunal
      filling (grade 1) and diabetes was statistically significant (p < 0.05).
      CONCLUSION: The administration of secretin improves visualization of the
      pancreatic ducts and helps in the evaluation of remnant pancreatic function after
      pancreatoduodenectomy.

PMID- 15505291
TI  - Spectrum of imaging findings after intestinal, liver-intestinal, or multivisceral
      transplantation: part 1, posttransplantation anatomy.

PMID- 15505292
TI  - Spectrum of imaging findings after intestinal, liver-intestinal, or multivisceral
      transplantation: part 2, posttransplantation complications.

PMID- 15505293
TI  - Blunt abdominal trauma: does the use of a second-generation sonographic contrast
      agent help to detect solid organ injuries?
AB  - OBJECTIVE: The objective of our study was to prospectively evaluate whether a
      second-generation sonography contrast agent (SonoVue) can improve the conspicuity
      of solid organ injuries (liver; spleen; or kidney, including adrenal glands) in
      patients with blunt abdominal trauma. SUBJECTS AND METHODS: Two hundred ten
      consecutive hemodynamically stable trauma patients underwent both abdominal
      sonography and CT at admission. The presence of solid organ injuries and the
      quality of sonography examinations were recorded. Patients with false-negative
      sonography findings for solid organ injuries in comparison with CT results
      underwent control sonography. If a solid organ injury was still undetectable,
      contrast-enhanced sonography was performed. Findings of admission, control, and
      contrast-enhanced sonograms were compared with CT results for their ability to
      depict solid organ injuries. Contrast-enhanced sonography was also performed in
      patients in whom a vascular injury (pseudoaneurysm) was shown on admission or
      control CT. RESULTS: CT findings were positive for 88 solid organ injuries in 71
      (34%) of the 210 patients. Admission, control, and contrast-enhanced sonograms
      had a detection rate for solid organ injury of 40% (35/88), 57% (50/88), and 80%
      (70/88), respectively. The improvement in the detection rate between control and
      contrast-enhanced sonography was statistically significant (p = 0.001). After
      exclusion of low-quality examinations, contrast-enhanced sonography still missed
      18% of solid organ injuries. Five vascular liver (n = 1) and spleen (n = 4)
      injuries (pseudoaneurysms) were detected on CT; all were visible on contrast
      enhanced sonography. CONCLUSION: Contrast-enhanced sonography misses a large
      percentage of solid organ injuries and cannot be recommended to replace CT in the
      triage of hemodynamically stable trauma patients. However, contrast-enhanced
      sonography could play a role in the detection of pseudoaneurysms.

PMID- 15505294
TI  - CT appearance of acute appendagitis.
AB  - OBJECTIVE: Our aim was to describe the spectrum of CT findings in patients with
      acute epiploic appendagitis and also to evaluate the changes seen with this
      condition. MATERIALS AND METHODS: Fifty patients diagnosed with acute epiploic
      appendagitis seen on contrast-enhanced CT were included in this study. The CT
      scans of the epiploic appendagitis were evaluated for the presence of colon wall
      thickening, a focal fatty center, inflammatory changes, location in relationship
      to the colon, size, and presence or absence of central high density within the
      fat. In 10 patients, the initial findings were compared with findings of follow
      up CT performed between 3 days-21 months after the first CT. RESULTS: The most
      common part of colon involved by acute epiploic appendagitis was the sigmoid
      colon (31/50), and the most common position was anterior to the colonic lumen
      (41/50). All 50 patients with acute epiploic appendagitis had a central fatty
      core surrounded by inflammation. Colon wall thickening was present in only two,
      and a central high-density focus was noted only in 27 of 50 patients. In 86%
      (43/50) of patients, the fatty central core was between 1.5 and 3.5 cm in length.
      The changes seen on follow-up CT varied, including increased density with a
      decrease in the size of the fatty central core, no change, complete resolution of
      findings, and minimal residual density. CONCLUSION: On CT, acute epiploic
      appendagitis has a predictable appearance in terms of location, size, and
      density. The most common finding on CT is a fat-density oval lesion with
      surrounding inflammation on the anterior aspect of the sigmoid colon. The changes
      on CT are not predictable in the 2-week to 6-month window.

PMID- 15505295
TI  - MRI of perianal Crohn's disease.

PMID- 15505296
TI  - Clostridium septicum infrarenal aortitis secondary to occult cecal
      adenocarcinoma.

PMID- 15505297
TI  - Contrast-enhanced sonographic appearance of hepatocellular carcinoma in patients
      with cirrhosis: comparison with contrast-enhanced helical CT appearance.
AB  - OBJECTIVE: We sought to investigate the efficacy of contrast-enhanced sonography
      using a second-generation contrast agent for the evaluation of hepatocellular
      carcinoma in patients with cirrhosis by comparing the results to those obtained
      with contrast-enhanced helical CT. SUBJECTS AND METHODS: Between October 2002 and
      March 2003, 74 patients with cirrhosis (60 men and 14 women; age range, 47-80
      years; mean age, 67 years) who had a single nodule of hepatocellular carcinoma
      were selected to be studied from a cohort of 437 patients with cirrhosis. The
      size range of the 74 nodules was 9-65 mm (mean, 28.2 mm). Twenty-eight (38%) were
      20 mm smaller (range, 9-20 mm; mean, 16.6 mm), and 46 (62%) were larger than 20
      mm (range, 21-65 mm; mean, 35.2 mm). Contrast-enhanced sonography was performed
      at a low mechanical index after IV administration of the contrast agent SonoVue.
      CT scans were obtained in all patients. The enhancement pattern related to tumor
      hypervascularity was analyzed. The chi-square test was used for statistical
      analysis. RESULTS: For the 28 hepatocellular carcinomas 20 mm or smaller,
      contrast-enhanced sonography showed 15 (53.6%) as hypervascular and 10 (35.7%) as
      avascular; three (10.7%) carcinomas were missed. On CT, 12 (42.9%) of the 28
      hepatocellular carcinomas appeared hypervascular, 13 (46.4%) appeared
      hypovascular, and three (10.7%) were missed. For the 46 hepatocellular carcinomas
      larger than 20 mm, contrast-enhanced sonography showed 42 (91.3%) as
      hypervascular and four (8.7%) as avascular. On CT, 35 (76.1%) hepatocellular
      carcinomas appeared hypervascular, eight (17.4%) appeared hypovascular, and three
      (6.5%) were missed. Differences between CT appearance of hepatocellular
      carcinomas and contrast-enhanced sonographic appearance of the carcinomas were
      not statistically significant. Concordance between contrast-enhanced sonographic
      and CT appearances was observed in 61 (82.4%) of 74 cases. CONCLUSION: Contrast
      enhanced sonography is similar to CT for detecting hepatocellular carcinoma
      hypervascularity. It could be complementary to conventional unenhanced sonography
      for evaluation of liver nodules.

PMID- 15505299
TI  - Hepatic nodular lesions associated with abnormal development of the portal vein.
AB  - OBJECTIVE: We reviewed the medical records including pathologic descriptions, CT
      images, MR images, and digital subtraction angiograms of three patients with
      hepatic lesions that were associated with abnormal development of the portal vein
      patent ductus venosus or congenital absence of the portal vein-to clarify the
      imaging characteristics of these abnormalities. CONCLUSION: Two-phase helical CT
      and MRI, including MR angiography and dynamic studies, are useful for the
      diagnosis of patent ductus venosus and congenital absence of the portal vein. MRI
      may more effectively reveal hepatic lesions than two-phase helical CT under such
      abnormal conditions in which the liver has only the arterial but not the portal
      blood supply.

PMID- 15505298
TI  - MDCT cholangiography with volume rendering for the assessment of patients with
      biliary obstruction.
AB  - OBJECTIVE: We sought to evaluate the diagnostic utility of MDCT cholangiography
      with volume rendering in the evaluation of patients with suspected biliary tree
      obstruction. SUBJECTS AND METHODS: MDCT was performed in 34 patients who were
      thought to have biliary obstruction. Portal venous phase scanning was initiated
      70 sec after the IV infusion of 150 mL of contrast agent, and no cholangiographic
      contrast agent was administered. Three-dimensional MDCT cholangiographic images
      were produced using volume rendering. ERCP was performed in 26 patients, and
      percutaneous transhepatic cholangiography (PTC) was performed in five patients;
      17 patients underwent biopsy or surgery. The findings on MDCT cholangiography
      were compared with those of ERCP, PTC, biopsy, or surgery. RESULTS: The correct
      diagnosis was made on MDCT cholangiography for 14 (93%) of the 15 patients with a
      biliary stone and in 16 (94%) of the 17 patients with malignant biliary
      obstruction. Microlithiasis in one patient could not be detected on MDCT
      cholangiography. One patient with polypoid adenocarcinoma and one patient with
      normal findings were incorrectly diagnosed with a biliary stone on the basis of
      MDCT cholangiography. In one of the two patients with a benign stricture, the
      stricture was incorrectly diagnosed as malignant. For the diagnosis of biliary
      stone, sensitivity and specificity of MDCT cholangiography were 93% and 89%,
      respectively. For the diagnosis of malignant obstruction, sensitivity and
      specificity were both 94%. The accuracy of the technique for the diagnosis of the
      cause of biliary obstruction was 83.3%. CONCLUSION: MDCT cholangiography with
      volume rendering is a noninvasive and fast imaging technique with high
      sensitivity and specificity for the diagnosis of the cause of biliary tree
      obstruction. It is a promising diagnostic tool for the assessment of patients
      with bile duct obstructions.

PMID- 15505300
TI  - Wilson's disease with chronic active hepatitis: monitoring by in vivo 31
      phosphorus MR spectroscopy before and after medical treatment.

PMID- 15505301
TI  - Flat colorectal lesions in asymptomatic adults: implications for screening with
      CT virtual colonoscopy.
AB  - OBJECTIVE: The clinical significance of flat lesions in colorectal cancer
      screening remains uncertain. The purpose of this study was to investigate the
      frequency, histology, and virtual colonoscopy detection of flat lesions in an
      asymptomatic screening population. SUBJECTS AND METHODS: The morphology of all
      detected polyps was prospectively recorded as flat or polypoid (sessile or
      pedunculated) in 1,233 consecutive asymptomatic adults who underwent same-day
      virtual colonoscopy and optical colonoscopy. A flat morphology was defined as a
      shallow plaquelike broad-based lesion with a height of less than one half of its
      width. RESULTS: Of 344 polyps of 6 mm or greater confirmed at optical
      colonoscopy, 17 (4.9%) were labeled as flat at both virtual colonoscopy and
      optical colonoscopy; 17 (4.9%), at optical colonoscopy only; and 25 (7.3%), at
      virtual colonoscopy only, yielding 59 total lesions in 52 (4.2%) of 1,233
      patients. Twenty-nine (49.2%) of 59 flat lesions were adenomatous, of which four
      measured 10 mm or greater and one 6- to 9-mm lesion was histologically advanced.
      None of the 148 diminutive flat lesions (< or = 5 mm) detected at optical
      colonoscopy was histologically advanced. Virtual colonoscopy prospectively
      detected 24 (82.8%) of 29 flat adenomas and 47 (80.0%) of all 59 flat lesions 6
      mm or greater. In comparison, the sensitivity of virtual colonoscopy for the
      detection of polypoid adenomas and all polypoid lesions of 6 mm or greater was
      86.2% (156/181, p = 0.58) and 81.0% (231/285, p = 0.86), respectively.
      CONCLUSION: Flat adenomas measuring 6 mm or greater are uncommon in a typical
      Western screening population, and advanced flat neoplasms are rare. The
      sensitivity of virtual colonoscopy for detecting flat lesions was similar to that
      of polypoid lesions. These results indicate that flat lesions are not a
      significant drawback for virtual colonoscopy screening.

PMID- 15505302
TI  - The effect of reconstruction algorithm on conspicuity of polyps in CT
      colonography.
AB  - OBJECTIVE: CT colonography studies to date have used a standard CT algorithm. To
      determine whether nonstandard algorithms may result in better performance of CT
      colonography, we conducted a prospective, blinded-observer study of the effect of
      the reconstruction algorithm on the conspicuity of colonic polyps and folds.
      SUBJECTS AND METHODS: CT colonography of patients with proven polyps, masses, or
      polypoid folds was performed on an MDCT scanner, and the images were
      reconstructed using the standard, soft, lung, and detail algorithms. Two
      experiments were performed. The first used four patient data sets of a short
      segment of colon (30-60 images), each reconstructed using all four algorithms and
      then viewed on a workstation in a four-on-one format that allowed all four
      reconstructions to be viewed simultaneously. The second used six sets of cut-film
      images (four or eight images each); images within each set differed only in the
      reconstruction algorithm used to generate them (eight-image sets were prepared
      with two different level settings). Twenty-one reviewers with varying levels of
      experience who were unaware of the purpose of the study were asked to rank the
      images within each set according to their value in the detection of either polyps
      or masses. RESULTS: Reviewers showed statistically significant differences in
      preference for the four algorithms (p = 0.037 in the computer-based experiment;
      for the cut-film experiment, p = 0.029 for the four-image sets and p = 0.041 for
      the eight-image sets). In the computer-based experiment, reviewers preferred the
      detail algorithm to the standard algorithm with an estimated probability of 0.67
      (95% confidence interval [CI], 0.57-0.75) and the soft algorithm over the
      standard algorithm with an estimated probability of 0.59 (95% CI, 0.51-0.66).
      However, reviewers with the most experience (having interpreted at least 250
      cases) preferred the soft algorithm over the standard algorithm by the same two
      to-one margin as observed for the detail algorithm. In contrast, the standard and
      detail algorithms were ranked similarly in the cut-film experiment, with the soft
      and lung algorithms ranked worst. CONCLUSION: To our knowledge, ours is the first
      observer study on the effect of the reconstruction algorithm on conspicuity of
      folds and polyps in CT colonography. Our results indicate significant differences
      in the reconstruction algorithms, with the soft and detail algorithms being
      preferred over the standard algorithm by experienced reviewers when interpreting
      images on a workstation. These results indicate the need for further research
      into the effect of reconstruction algorithms on CT colonography.

PMID- 15505303
TI  - Feasibility of MDCT Colonography in ultra-low-dose technique in the detection of
      colorectal lesions: comparison with high-resolution video colonoscopy.
AB  - OBJECTIVE: The purpose of this study was to assess the feasibility of MDCT
      colonography in an ultra-low-dose technique in the detection of endoluminal
      colonic lesions compared with high-resolution video colonoscopy. SUBJECTS AND
      METHODS: After standard bowel cleansing, 137 patients (77 men, 60 women; mean [+/
      SD] age, 57.1 +/- 11.3 years) underwent high-resolution video colonoscopy within
      2 hr after ultra-low-dose MDCT colonography had been performed. Ultra-low-dose
      MDCT colonography was performed with patients in the supine position only using
      10 mAs (effective weighted CT dose index, 0.94 mGy). After mathematic noise
      reduction by nonlinear gaussian filter chains, using dedicated software (ECCET),
      images were analyzed by two blinded observers in simultaneously displayed
      interactive 2D and 3D modes. Findings of ultra-low-dose MDCT colonography were
      compared with the results obtained with high-resolution video colonoscopy.
      RESULTS: Calculated effective doses were 0.7 and 1.2 mSv for men and women,
      respectively. Ultra-low-dose MDCT colonography detected 84 (62%) of 135 lesions:
      11 (78.6%) of 14 large polyps (> 10 mm), 12 (85.7%) of 14 medium polyps (9.9-5
      mm), and 61 (57%) of 107 small polyps (< 5 mm). On a patient-by-patient basis, an
      overall sensitivity of 70.3% with a specificity of 80.8% was calculated. False
      positive findings were seen mostly for small lesions (eight medium and 29 small
      lesions). Two of the three false-negative lesions were retrospectively detected
      in contrast-enhanced cleansing fluid; one was a flat lipoma not detectable on
      ultra-low-dose MDCT colonography. CONCLUSION: Despite an effective dose of
      approximately 1 mSv, MDCT colonography using an ultra-low-dose technique performs
      as well as MDCT colonography with a standard dose, according to published data.
      After mathematic noise reduction, 82% of polyps larger than 5 mm can be detected.

PMID- 15505304
TI  - Frequency and relevance of the "small-bowel feces" sign on CT in patients with
      small-bowel obstruction.
AB  - OBJECTIVE: We sought to determine the incidence of the "small-bowel feces" sign
      (SBFS) in patients with small-bowel obstruction (SBO) and whether it can be used
      to accurately locate the point of obstruction. SUBJECTS AND METHODS: From
      November 2002 until March 2003, 34 consecutive adult patients with CT findings of
      small-bowel obstruction were prospectively evaluated. The CT findings used to
      diagnose small-bowel obstruction were a dilated proximal small bowel and a
      collapsed distal small bowel and colon. CT scans were evaluated to determine the
      degree of obstruction (mild, moderate, or high-grade), the presence or absence of
      the SBFS (defined as particulate-type material in the dilated small bowel), the
      location of the SBFS in relation to the transition zone, and the cause of the
      obstruction. Mild obstruction was defined as a slight discrepancy between the
      caliber of the proximal and that of the distal small bowel; moderate SBO was
      defined as a discrepancy of 50% or more between the calibers of the proximal and
      the distal small bowel; and high-grade SBO was considered to be present if the
      distal small bowel and the colon had collapsed. The cause of the obstruction was
      determined from surgical findings or a combination of CT findings, follow-up
      barium studies, and clinical assessment. RESULTS: The SBFS was present in 19
      (55.9%) of 34 patients with SBO. The degree of SBO was mild in six, moderate in
      11, and high-grade in 17 of the patients. The SBFS was present in one of the six
      patients (16.6%) with mild, eight (72.7%) of the 11 with moderate, and 10 (58.8%)
      of the 17 with high-grade SBO. In all patients in whom the SBFS was present, the
      particulate material could be traced to the point of transition and was most
      conspicuous in the transition zone. The length of fecallike material ranged from
      2 to 25 cm and was longer in moderate and high-grade SBO than in mild SBO. The
      cause of the SBO was an adhesion in 20 patients, a hernia in four patients,
      Crohn's disease in four patients, a tumor in three patients, and other
      miscellaneous causes in three patients. CONCLUSION: When present on CT, the SBFS
      can be used to help locate the transition zone in patients with SBO. The sign is
      present more frequently in patients with moderate and high degrees of SBO.

PMID- 15505305
TI  - Intraductal papillary mucinous neoplasms of the pancreas: CT patterns of
      recurrence and multiobserver performance in detecting recurrent neoplasm after
      surgical resection.
AB  - OBJECTIVE: The purposes of our study were to describe the CT appearance of
      recurrent intraductal papillary mucinous neoplasms of the pancreas after surgical
      resection and estimate the performance of CT in detecting recurrent neoplasms.
      MATERIALS AND METHODS: A single unblinded reviewer characterized the presence and
      appearance of recurrent intraductal papillary mucinous neoplasms on 66 CT scans
      of 17 patients with proven recurrence, noting location and appearance of
      recurrent neoplasm. These results, described in this article, were summarized in
      tabular format and shown to three blinded observer. The observers then evaluated
      one postoperative CT examination from every patient at our institution who
      underwent surgical removal of intraductal papillary mucinous neoplasms (n = 45)
      for the presence or absence of local or distant recurrence. RESULTS: The
      unblinded reviewer found 11 cases of local recurrence. Extrapancreatic local
      recurrences tend to have solid components (5/6), tend to be located adjacent to
      the resection margin (5/6), and may exhibit vascular invasion (2/6).
      Intrapancreatic neoplasms are usually cystic (4/5). Nine patients had distant
      metastases. Prospective sensitivity for recurrent tumor ranged from 76% (13/17)
      to 94% (16/17). Sensitivity for local recurrence ranged from 55% (6/11) to 82%
      (9/11). Specificity ranged from 79% (22/28) to 96% (27/28). Interobserver
      agreement for predicting recurrence was moderate to substantial (kappa = 0.51
      0.65). CONCLUSION: Locally recurrent intraductal papillary mucinous neoplasms of
      the pancreas tend to be either extrapancreatic and solid at the resection margin
      or intrapancreatic and cystic. CT can detect most recurrent intraductal papillary
      mucinous neoplasms of the pancreas with moderate to substantial interobserver
      agreement.

PMID- 15505306
TI  - Diagnosis of cavitating mesenteric lymph node syndrome in celiac disease using
      MRI.

PMID- 15505307
TI  - Testicular size and vascular resistance before and after hydrocelectomy.
AB  - OBJECTIVE: We sought to determine whether there is an association between
      hydroceles and testicular size and vascular resistance. SUBJECTS AND METHODS:
      Twenty-three patients with a mean age of 42.8 years who had a unilateral
      idiopathic hydrocele and who underwent unilateral hydrocelectomy were included in
      the study. Testicular size and resistive (RI) and pulsatility (PI) indexes of the
      intratesticular arteries on the involved and uninvolved sides were measured
      before and after the hydrocelectomy. RESULTS: We found statistically significant
      differences in the testicular volumes between the normal side (mean +/- SD, 15.40
      +/-3.41 mL) and the side with the hydrocele (20.67 +/- 4.01 mL) before surgery (p
      < 0.001) and in the volumes in the side with the hydrocele before (20.67 +/- 4.01
      mL) and after (16.20 +/- 2.99 mL) surgery (p < 0.001). No such a difference in
      volume was seen in the normal side before (15.40 +/- 3.41 mL) and after (15.28 +/
      3.24 mL) surgery (p = 0.200). The mean decrease in volume in the testis with the
      hydrocele after hydrocelectomy was 21%. There were statistically significant
      differences of RI and PI values between the normal testis (0.59 +/- 0.07 and 1.02
      +/- 0.34, respectively) and the testis with hydrocele (0.79 +/- 0.11 and 1.70 +/-
      0.56, respectively) before surgery (p < 0.001). In the testis with the hydrocele,
      we found a statistically significant decrease in RI and PI values (0.62 +/- 0.05
      and 1.00 +/- 0.14, respectively) of intratesticular arteries after surgery (p <
      0.001). The mean decreases in RI and PI values after hydrocelectomy were 21% and
      36%, respectively. CONCLUSION: There is an association between the development of
      an idiopathic hydrocele and testicular size and vascular resistance. We believe
      that the increase in volume and vascular resistance is due to an increase in
      impedance to venous and lymphatic flow.

PMID- 15505308
TI  - Differentiation of renal clear cell carcinoma and renal papillary carcinoma using
      quantitative CT enhancement parameters.
AB  - OBJECTIVE: The purpose of our study was to evaluate quantitative multiphasic CT
      enhancement patterns of malignant renal neoplasms to enable lesion
      differentiation by their enhancement characteristics. We used a new method to
      standardize enhancement measurement in lesions on multiphasic CT not being
      influenced by intrinsic factors like cardiac output. CONCLUSION: The new
      correction method is a simple tool for excluding intrinsic influences on the
      enhancement of lesions. Quantitative enhancement evaluation with this method of
      the influence of intrinsic factors enables accurate differentiation between renal
      clear cell carcinoma and renal papillary carcinoma.

PMID- 15505309
TI  - Symptomatic perirenal serous cysts of mullerian origin mimicking renal cysts on
      CT.
AB  - OBJECTIVE: Our aim was to describe the clinical presentation, CT appearance, and
      management of a series of symptomatic perirenal serous cysts of mullerian origin,
      confirmed by laparoscopic resection. CONCLUSION: Perirenal serous cysts of
      mullerian origin are uncommon lesions that may present as large symptomatic
      perirenal cystic masses mimicking exophytic renal cysts on CT. Serous cyst of
      mullerian origin should be considered in the differential diagnosis when CT
      reveals a large solitary perirenal cyst in a woman with flank or abdominal pain
      or both. Laparoscopic resection may be an effective treatment of such cysts.

PMID- 15505310
TI  - Imaging features of primary nonurachal adenocarcinoma of the bladder.
AB  - OBJECTIVE: Our aim was to describe the imaging appearances of primary nonurachal
      adenocarcinoma of the bladder. CONCLUSION: A diffusely thickened bladder wall
      with stranding in the surrounding fat is a frequent finding of primary bladder
      adenocarcinoma. These malignancies are classified at a high stage at presentation
      with locally advanced disease, and a large proportion of patients have distant
      metastases, with the peritoneum, lymph nodes, and lung appearing to be favored
      sites.

PMID- 15505311
TI  - Papillary renal cell carcinoma containing fat without calcification mimicking
      angiomyolipoma on CT.

PMID- 15505313
TI  - Reflux in the left ovarian vein: analysis of MDCT findings in asymptomatic women.
AB  - OBJECTIVE: The aim of this study was to clarify the CT features of ovarian vein
      reflux in asymptomatic women and to determine the possible cause of the reflux.
      MATERIALS AND METHODS: One hundred ten multiparous or uniparous and 41
      nulliparous asymptomatic women were examined on MDCT. Degree, pathway, and
      associated findings of ovarian vein reflux were evaluated. We measured the
      diameters of the left renal vein (LRV), the ovarian veins, and the parauterine
      veins. Ratios of LRV diameters (lateral-aortomesenteric) were obtained. These
      data were then compared between the women with reflux and those without reflux.
      RESULTS: Reflux was found in 44% (48/110) of parous and 5% (2/41) of nulliparous
      women. Reflux flowed into the right ovarian vein through the parauterine and
      uterine veins in 25 women. Twenty-four of these 25 women were multiparous. In
      these cases, the parauterine veins showed varicose dilation (5.9 +/- 1.6 mm [mean
      +/- SD]). There was a statistically significant difference in left ovarian vein
      diameter (8.3 +/- 2.1 mm vs 4.9 +/- 1.3 mm, p < 0.0001) between parous women with
      reflux and those without reflux, respectively. The LRV diameter ratio (lateral
      aortomesenteric) was also statistically significant (3.6 +/- 1.3 vs 1.7 +/- 0.7,
      p < 0.0001) between the same two groups. CONCLUSION: Reflux into the left ovarian
      vein is seen up into the contralateral ovarian plexus by passing through the
      dilated parauterine and uterine veins. This CT finding is common in asymptomatic
      multiparous women. Narrowing of the LRV at its aortomesenteric portion can be one
      of the causes of such reflux.

PMID- 15505312
TI  - Diagnostic value of hysterosalpingography in the detection of intrauterine
      abnormalities: a comparison with hysteroscopy.
AB  - OBJECTIVE: The purpose of this study was to evaluate the diagnostic accuracy of
      hysterosalpingography (HSG) in comparison with hysteroscopy in the detection of
      intrauterine abnormality in infertile patients. MATERIALS AND METHODS: Seventy
      eight patients being investigated for infertility and undergoing HSG and
      hysteroscopy were studied retrospectively. Radiologic findings on HSG, including
      single or multiple filling defects and uterine wall irregularities, were
      evaluated and compared with hysteroscopic findings, which were considered the
      reference standard. RESULTS: HSG showed a sensitivity of 81.2% compared with that
      of hysteroscopy and a specificity of 80.4%, with a positive predictive value of
      63.4% and a negative predictive value of 83.7%. HSG also had a false-negative
      rate of 90% and a false-positive rate of 21.8%. Overall agreement between the two
      procedures was 73%. CONCLUSION: HSG is still a useful screening test for the
      evaluation of the uterine cavity in the study of primary or secondary
      infertility. In addition, HSG provides information concerning the assessment of
      tubal morphology and patency. We believe that these two procedures are
      complementary in the evaluation of the uterine cavity.

PMID- 15505314
TI  - Therapeutic efficacy and safety of percutaneous radiofrequency ablation of
      hepatocellular carcinoma abutting the gastrointestinal tract.
AB  - OBJECTIVE: The purpose of this study was to evaluate the therapeutic efficacy and
      safety of percutaneous radiofrequency ablation in the treatment of hepatocellular
      carcinomas abutting the gastrointestinal tract. MATERIALS AND METHODS: Forty-one
      patients with hepatocellular carcinomas abutting the gastrointestinal tract
      underwent sonographically guided percutaneous radiofrequency ablation. Forty-one
      tumors (1.2-4.3 cm in maximum diameter) had parts 5 mm or greater (or at least
      one quarter of their circumferences) abutting the stomach in 23 patients and the
      colon in 18 patients. Thirty tumors were ablated with internally cooled
      electrodes and 11 with multitined expandable electrodes. All patients were
      followed up for at least 1 year after ablation. Therapeutic efficacy and safety
      were evaluated with follow-up sonography and multiphase helical CT. RESULTS: At 1
      month follow-up CT, three (7%) of the 41 tumors showed residual unablated tumor
      in the ablation zone. Of the remaining 38 hepatocellular carcinomas (93%) with no
      evidence of residual unablated tumor, four (11%) showed local tumor progression
      in the ablation zones on subsequent follow-up CT. We observed one major
      complication-a small perihepatic abscess-that needed specific treatment.
      CONCLUSION: Percutaneous radiofrequency ablation is an effective and safe
      technique for treating hepatocellular carcinomas abutting the gastrointestinal
      tract.

PMID- 15505315
TI  - Combined radiofrequency and alcohol injection for percutaneous hepatic tumor
      ablation.
AB  - OBJECTIVE: We sought to determine if alcohol potentiates radiofrequency energy by
      obtaining larger ablative volumes in 30 liver tumors in human patients. SUBJECTS
      AND METHODS: We compared two groups of patients: one group treated with
      radiofrequency ablation alone (radiofrequency-alone group), and a second group
      treated with radiofrequency ablation and immediate prior injection of alcohol
      (combined group). The radiofrequency-alone group comprised 20 ablations (mean
      diameter, 8.4 cm; colorectal cancer metastases [n = 15]; other metastases [n =
      5]). The combined group consisted of 30 radiofrequency ablations (mean diameter,
      8.8 cm; metastatic colorectal cancer [n = 17]; other metastases [n = 8]; and
      hepatocellular carcinoma [n = 5]) treated with alcohol injection immediately
      before radiofrequency ablation. The amount of alcohol injected was determined by
      the size and location of tumors. Preprocedural laboratory tests (complete blood
      cell count with differential, liver function tests, and coagulation parameters)
      were performed in all patients, along with pre- and postprocedural CT, MRI, and
      PET. Measurements of tissue necrosis were obtained on the postprocedural CT scans
      and MR images. Volumes of necrosis calculated in each group were corrected for
      the number of radiofrequency applications and were statistically compared using
      the Student's t test. In addition, tissue impedances obtained during the
      radiofrequency ablation procedure were compared between the two groups. RESULTS:
      The mean ablation volumes for the radiofrequency-alone group were 32.3 cm(2)
      (median, 28.6 cm(2); range, 14.4-61.8 cm(2)) and for the combined group, 84.6
      cm(2) (median, 78.3 cm(2); range, 34.6-149 cm(2)). The difference in the necrosis
      volumes was significantly larger (p < 0.0001) in the combined group. Overall, the
      combined treatment group underwent fewer radiofrequency applications per session.
      Tissue impedance during radiofrequency ablation was higher in the combined group
      (mean, 62.7 vs 57.3 Omega in the radiofrequency alone group; p = 0.0005) at
      comparable times during the ablations. No major complications were seen in either
      group. CONCLUSION: Percutaneous radiofrequency ablation appears to be potentiated
      by immediate prior alcohol injection into the tumor. Consistently larger lesions
      are obtainable in fewer sessions, without any increase of complications, using
      the combined method.

PMID- 15505316
TI  - Percutaneous gastrostomy for treating dilatation of the bypassed stomach after
      bariatric surgery for morbid obesity.
AB  - OBJECTIVE: Retrospective analysis was performed to determine the safety and
      effectiveness of percutaneous gastrostomy for treating distention of the bypassed
      stomach after gastric bypass for morbid obesity. MATERIALS AND METHODS: Eight
      patients with morbid obesity and Roux-en-Y gastric bypass underwent percutaneous
      radiologic gastrostomy for postoperative decompression of the bypassed stomach.
      Four patients underwent gastrostomy on the fourth day after surgery: two in the
      early postoperative period (< or = 30 days after surgery) and two in the late
      postoperative period (6, 11 months after the procedure). Procedures were
      performed using combinations of fluoroscopic, CT, and sonographic guidance. T
      tacks and a variety of locking pigtail drainage catheters were placed in seven
      patients. RESULTS: Gastrostomy placement was technically successful in all
      patients. Seven of eight patients experienced resolution of symptoms. Gastrostomy
      catheters were in place for a mean of 31 days. Two complications occurred.
      Periprocedural peritonitis in one patient with underlying small-bowel obstruction
      required surgical intervention. One wound infection was treated with antibiotics
      and local wound care. No catheters became dislodged or obstructed. Four patients
      treated during the early postoperative period had resolution of symptoms after
      tube placement and recovered uneventfully. Three of four patients presenting
      during the intermediate or late postoperative periods had temporary resolution of
      symptoms, but all eventually required surgical intervention. CONCLUSION: In the
      absence of complete small-bowel obstruction, percutaneous radiologic gastrostomy
      provides safe and effective decompression of the excluded gastric remnant after
      Roux-en-Y gastric bypass. Gastrostomy tube placement after the early
      postoperative period is temporizing, with surgical intervention eventually
      required.

PMID- 15505317
TI  - Removal of retrievable esophageal and gastrointestinal stents: experience in 113
      patients.
AB  - OBJECTIVE: Although there are frequent clinical situations in which esophageal
      and gastrointestinal stents should be removed, nonsurgical stent removal has been
      difficult. The purpose of our study was to describe the safety and efficacy of
      removing the retrievable nitinol stents with a retrieval hook. MATERIALS AND
      METHODS: Under fluoroscopic guidance, the removal of 119 esophageal, six
      gastroduodenal, and five rectal retrievable stents was attempted in 113 patients
      using a retrieval hook. Indications for stent removal included migration (n =
      35), severe pain (n = 23), formation of a new stricture (n = 13), incomplete
      stent expansion (n = 7), airway compression (n = 2), esophagorespiratory fistula
      (n = 2), malpositioned stent (n = 1), and hematemesis (n = 1). The remaining 46
      stents were electively removed. RESULTS: Of the 130 stents, 127 (97.7%) were
      successfully removed despite the following difficulties: untied drawstrings (n =
      4), separation of the stent (n = 3), and fracture (n = 2) or disconnection (n =
      2) of a retrieval hook. The removal procedure failed in three cases (2.3%). The
      causes of failure were the inability to place the hook into the migrated stent (n
      = 2) and a tight stricture above the migrated stent (n = 1). The procedure
      related complications included minor (n = 4) and major (n = 1) bleeding and
      intramural rupture (n = 3). One patient died of major bleeding after removal of
      an esophageal stent. CONCLUSION: The stent retrieval hook is useful for removing
      retrievable esophageal and gastrointestinal stents.

PMID- 15505318
TI  - Subtraction CT angiography of the lower limbs: a new technique for the evaluation
      of acute arterial occlusion.

PMID- 15505319
TI  - Sonography and MRI of the shoulder: comparison of patient satisfaction.
AB  - OBJECTIVE: MRI and sonography are both used to evaluate patients with painful
      shoulders. This study was conducted to compare patients' perceptions and
      satisfaction with both tests. SUBJECTS AND METHODS: One hundred eighteen patients
      with shoulder pain and a clinically suspected rotator cuff tear underwent both
      MRI and sonography and filled out satisfaction surveys after both tests. Patients
      were asked the following questions: Did the test cause pain? If it did, they were
      asked to grade the pain on a scale of 1-10 (1, minimal pain; 10, severe pain).
      Did the test take too long? Would they be willing to undergo the test again? How
      would they grade their overall satisfaction with the test (1, poor; 2, fair; 3,
      good; 4, very good; and 5, excellent)? Which test did they prefer if both were
      equally accurate? RESULTS: Sonography caused pain above the baseline in 39
      patients, with an average pain score (mean +/- SD) of 5.4 +/- 2.3, and MRI caused
      pain above the baseline in 40 patients, with an average pain score of 6.1 +/- 2.7
      (p = 0.36). Two patients thought the sonography examination took too long, and 28
      patients though the MRI examination was too long (p < 0.001). The average
      satisfaction level for sonography was 4.3 +/- 0.7 and for MRI, 3.6 +/- 1.2 (p <
      0.001). The satisfaction score was higher for sonography in 54 patients, higher
      for MRI in 13 patients, and the same for both in 50 patients (p < 0.001). All
      patients were willing to repeat the sonography, but 10 patients were unwilling to
      repeat the MRI (p = 0.002). Ninety-three patients preferred sonography, eight
      patients preferred MRI, and 17 patients had no preference (p < 0.001).
      CONCLUSION: Most patients with shoulder pain prefer sonography to MRI.

PMID- 15505320
TI  - MRI of large intraosseous lesions in patients with inflammatory arthritis.
AB  - OBJECTIVE: The purpose of our study was to evaluate on MRI the occurrence of
      large cystlike intraosseous lesions in patients with inflammatory arthritis.
      SUBJECTS AND METHODS: We prospectively reviewed contrast-enhanced MR images of
      128 hands and wrists in 44 patients with clinical presentation of inflammatory
      arthritis. Large lesions (> or = 1 cm) found on MR images were further evaluated
      for the presence of a cortical break and intraarticular extension. These data
      were correlated with clinical and laboratory findings and the duration of
      arthritis. RESULTS: We found 26 patients with rheumatoid arthritis, seven with
      psoriatic arthritis, two with systemic lupus erythematosus, one with HIV
      associated arthritis, one with mixed connective tissue disorder, one with
      paraneoplastic-associated arthritis, one with inflammatory bowel disease
      arthritis, and five patients with early unclassified inflammatory arthritis.
      Twelve patients had 16 large intraosseous lesions, none of which were detected on
      available radiographs (availability of radiographs for large erosions was 75%). A
      cortical break with intraarticular extension of the large lesions was seen in 12
      cases. Four lesions were not intraarticular. CONCLUSION: Even large intraosseous
      lesions may be occult on radiography. MRI is a superior technique for detecting
      these lesions in the small joints of the hand and wrist in inflammatory
      arthritis. Although large intraosseous erosions often communicate with joints, we
      observed four large purely intraosseous enhancing lesions without intraarticular
      connection. Patients with large erosions have a longer duration of inflammatory
      arthritis.

PMID- 15505321
TI  - Sonography of the rotator cuff: analysis of interobserver variability.
AB  - OBJECTIVE: The purpose of our study was to determine the interobserver
      variability in the sonographic evaluation of the rotator cuff. SUBJECTS AND
      METHODS: Two radiologists independently scanned 61 patients with shoulder pain.
      Each radiologist categorized the rotator cuff as normal, partially torn, or fully
      torn. When a tear was present, the tendons involved were specified. All diagnoses
      were made prospectively without knowledge of the findings of the other
      radiologist. RESULTS: The radiologists were in full agreement in the
      categorization of 92% (56/61) of the patients. In four of the five discrepant
      cases, the disagreement was whether there was a full-thickness or a partial
      thickness tear. The radiologists were in agreement concerning which tendons were
      involved in 80% (41/51) of the patients in whom a tear was detected by both
      observers. In all 10 discrepant cases, the disagreement was whether a tear
      involved both the supraspinatus and infraspinatus tendons or was isolated to one
      or the other of these tendons. CONCLUSION: The level of interobserver variability
      in the sonographic detection and characterization of rotator cuff tears is low.

PMID- 15505322
TI  - Detection of meniscal tears and marrow lesions using coronal MRI.
AB  - OBJECTIVE: The usefulness of coronal images in addition to sagittal images for
      detection of additional meniscal injuries or bone lesions has been questioned.
      Some authors believe meniscal tears are rarely seen only in the coronal plane. We
      performed a retrospective review of coronal and sagittal MR images of the knee to
      determine whether coronal imaging resulted in the detection of any additional
      meniscal tears or bone lesions when compared with sagittal MRI of the knee alone.
      MATERIALS AND METHODS: Two musculoskeletal radiologists retrospectively reviewed
      200 consecutive sets of MR images of the knee by consensus. Both observers
      recorded their retrospective findings on sagittal proton density images, sagittal
      and coronal T2-weighted images, and coronal T1-weighted images. Findings recorded
      were those of meniscal tears, bone marrow abnormalities, and bone lesions.
      RESULTS: On these 200 consecutive sets of MR images of the knee, 114 meniscal
      tears were shown. Ninety-three meniscal tears were shown on sagittal proton
      density images only. One hundred fourteen meniscal tears were seen on sagittal
      proton density and coronal T1- and T2-weighted images. Use of coronal images
      resulted in the confident detection of 21 additional meniscal tears not well seen
      on sagittal proton density images alone. Twelve of the 21 additional meniscal
      tears were seen on coronal T1- and T2-weighted images. Nine of the 21 additional
      meniscal tears were seen only on coronal T1-weighted images. Most of these
      additional meniscal tears were in the body of the meniscus. These 21 additional
      meniscal tears were confirmed arthroscopically. Eight marrow lesions were well
      characterized only on coronal T1-weighted images. Five were osteochondral
      lesions, one was an intraosseous hemangioma, and two were microfractures.
      CONCLUSION: Coronal MR images of the knee allowed better detection and
      characterization of some meniscal tears than sagittal images alone. Radial
      meniscal tears, bucket-handle tears, and horizontal tears in the body of the
      meniscus may be difficult to characterize in the sagittal plane alone. Use of
      coronal T1-weighted images, rather than coronal T2-weighted or sagittal proton
      density images alone, allows accurate characterization of some additional marrow
      lesions. The addition of a T1-weighted sequence in the coronal plane adds only 1
      min 30 sec to the scanning time.

PMID- 15505324
TI  - Musculoskeletal MRI at 3.0 T: initial clinical experience.

PMID- 15505323
TI  - Chance fracture of the upper thoracic spine.

PMID- 15505325
TI  - Chronic scapulothoracic bursitis associated with thoracoplasty.

PMID- 15505326
TI  - Analysis of 51 tibial triplane fractures using CT with multiplanar
      reconstruction.
AB  - OBJECTIVE: We determined the most common patterns of triplane fractures and
      assessed the risk of epiphyseal separation in each pattern. MATERIALS AND
      METHODS: Fifty-one children with tibial triplane fractures underwent CT, and the
      resultant scans underwent multiplanar reconstruction. We categorized epiphyseal
      and physeal involvement, the number of fragments, the appearance of the Salter
      Harris fracture in each plane, and the degree of separation of the epiphyseal
      fragments. RESULTS: The classic two-fragment type of fracture with medial
      epiphyseal extension occurred most frequently (33/51). All three-fragment types
      (8/51) of fractures resulted in a separate anterolateral fragment. Extension to
      the medial malleolus was common (12/51). None of the four reported fractures
      types involving anteromedial physeal separation was seen. Children with
      epiphyseal separation requiring surgery were older (odds ratio [OR] = 1.7) and
      had plafond involvement (OR = 5), CONCLUSION: CT and multiplanar reconstruction
      of triplane fractures improve the understanding of patterns of injury and their
      relative prevalence.

PMID- 15505327
TI  - CT of congenital lung lesions in pediatric patients.

PMID- 15505328
TI  - Sonographically guided aspiration of cerebrospinal fluid pseudocysts in children
      and adolescents.
AB  - OBJECTIVE: Cerebrospinal fluid (CSF) pseudocyst formation is an uncommon cause of
      ventriculoperitoneal shunt malfunction in children. Traditional staged treatment
      consists of shunt externalization, antibiotics, and later shunt revision and
      internalization. We sought to evaluate whether sonographically guided pseudocyst
      aspiration to alleviate acute symptoms and to exclude CSF infection could obviate
      shunt externalization and expedite the care of these patients. CONCLUSION:
      Sonographically guided CSF pseudocyst aspiration is an effective technique,
      allowing exclusion or confirmation of infection and providing relief of abdominal
      symptoms. In patients with sterile collections, staged surgical revision with
      shunt externalization can be avoided, speeding and simplifying treatment.

PMID- 15505329
TI  - Computer-aided detection in diagnostic mammography: detection of clinically
      unsuspected cancers.
AB  - OBJECTIVE: We had two objectives: to determine the percentage of women presenting
      with clinical findings whose diagnostic mammogram led to detection of a breast
      cancer at a site distant from the original clinical complaint and to assess the
      performance of computer-aided detection (CAD) on diagnostic mammography.
      MATERIALS AND METHODS: Three institutions contributed consecutive cases in which
      a mammogram was obtained to evaluate a clinical finding, after which a histologic
      diagnosis of breast cancer was made. Clinical data and the mammograms were
      reviewed to determine the nature of the clinical findings and to document the
      location and characteristics of 212 biopsy-proven cancers in 197 patients who met
      the study criteria. Standard four-view breast mammograms were then analyzed by a
      CAD system. RESULTS: The most common clinical finding was a palpable mass (90%,
      177/197), with nipple discharge (5%, 9/197), focal tenderness or pain (2%,
      5/197), and miscellaneous complaints (3%, 6/197) also noted. Two separate cancers
      were found in 7.6% (15/197) of the cases. In another 7.6% (15/197) of the cases,
      the single diagnosed cancer was not at the location of the specific clinical
      finding. The CAD system correctly marked 87% (26/30) of those cancers that were
      clinically unsuspected (i.e., not at the location of the clinical finding).
      CONCLUSION: Breast cancers occurred at locations other than the site of the
      presenting clinical finding in 15% (30/197) of patients undergoing diagnostic
      mammography in whom a cancer was detected. CAD identified 87% of these
      incidentally detected cancers and may therefore be useful as a detection aid to
      the radiologist when interpreting diagnostic mammograms.

PMID- 15505330
TI  - Intracystic papillary carcinoma of the breast with invasion.

PMID- 15505331
TI  - A Web-based ACR index for radiological diagnoses.
AB  - OBJECTIVE: We created an online computer system that allows radiologists to
      access the American College of Radiology (ACR) index for radiologic diagnoses
      from any Web browser. CONCLUSION: A total of 11,260 indexes (10 anatomic, 722
      pathologic, 90 subanatomic, and 10,438 subpathologic) were integrated into this
      online system. Users can navigate the entire ACR hierarchic indexing structure
      with easy-to-use cascading dropdown lists. This password-protected system also
      allows free-text searches, ACR index searches, and bookmark functions. We have
      used this system in our departmental intranet for more than 2 years.

PMID- 15505332
TI  - Intraaortic balloon pump mimicking catheter tip fracture.

PMID- 15505333
TI  - Endovascular management of May-Thurner syndrome.

PMID- 15505334
TI  - Ubiquitin signals in the developing acrosome during spermatogenesis of rat
      testis: an immunoelectron microscopic study.
AB  - The localization of ubiquitin (UB) signals in the acrosomes of rat spermiogenic
      cells was investigated by immunoelectron microscopy using two anti-UB antibodies:
      UB1, reacting with ubiquitinated proteins and free UB; and FK1, recognizing
      polyubiquitinated proteins but not monoubiquitinated proteins or free UB.
      Labeling of UB by UB1 (UB1 signal) was detected in the acrosomes at any stage of
      differentiation. In step 1 spermatids, UB1 signals were detected on the
      cytoplasmic surface and in the matrix of transport vesicles located between the
      trans-Golgi network and the acrosome. Weak signals were detected in acrosomal
      granules within acrosome vesicles that had not yet attached to the nucleus. In
      step 4-5 spermatids, the acrosome vesicles had enlarged and attached to the
      nucleus. Strong gold labeling was noted in a narrow space between the outer
      acrosomal membrane and the developing acrosomal granule, where a dense fibrous
      material was observed on routine electron microscopy, whereas the acrosomal
      granule was weakly stained by UB1 antibody. In step 6-8 spermatids, UB1 signals
      were detected in the fibrous material that expanded laterally to form a narrow
      electronless dense zone between the acrosomal granule and the outer acrosomal
      membrane. Labeling in the acrosomal granule increased. In step 9-11 spermatids,
      UB1 signals were confined to the narrow zone from the tip of the head to the
      periphery of the ventral fin. The matrix of the acrosome was weakly stained. In
      epididymal sperm, UB1 labeling in the acrosome decreased without any
      pretreatment, whereas staining was noted in a spot in the neck region and in the
      dorsal fin after trypsin digestion. On the other hand, the staining pattern with
      FK1 was quite different from that with UB1. The trans-Golgi network was weakly
      stained but the cis-Golgi network was strongly stained. The dense fibrous
      material just beneath the outer membrane was never stained with FK1. The results
      suggest that UB on the surface of transport vesicles is involved in anterograde
      transport from the Golgi apparatus to the acrosome. The physiological role of UB
      in acrosomes is not clear. Two candidates for monoubiquitinated proteins in the
      acrosome, which have a UB-interacting motif, were found by cyber screening.

PMID- 15505335
TI  - Perlecan immunolocalizes to perichondrial vessels and canals in human fetal
      cartilaginous primordia in early vascular and matrix remodeling events associated
      with diarthrodial joint development.
AB  - The aim of this study was to ascertain how perlecan was localized in human fetal
      cartilaginous joint rudiment tissues. Perlecan was immunolocalized in human fetal
      (12-14-week-old) toe, finger, knee, elbow, shoulder, and hip joint rudiments
      using a monoclonal antibody to domain-1 of perlecan (MAb A76). Perlecan had a
      widespread distribution in the cartilaginous joint rudiments and growth plates
      and was also prominent in a network of convoluted hairpin loop-type vessels at
      the presumptive articulating surfaces of joints. Perlecan was also present in
      small perichondrial venules and arterioles along the shaft of the developing long
      bones, small blood vessels in the synovial lining and joint capsules, and in
      distinctive arrangements of cartilage canals in the knee, elbow, shoulder, and
      hip joint rudiments. Perlecan was notably absent from CD-31-positive metaphyseal
      vessels in the hip, knee, shoulder, and fingers. These vessels may have a role in
      the nutrition of the expanding cell populations in these developing joint tissues
      and in the establishment of the secondary centers of ossification in the long
      bones, which is essential for endochondral ossification.

PMID- 15505337
TI  - High-resolution visualization of the microbial glycocalyx with low-voltage
      scanning electron microscopy: dependence on cationic dyes.
AB  - The microbial glycocalyx is composed of a variety of polyanionic
      exopolysaccharides and plays important roles in microbial attachment to different
      substrata and to other cells. Here we report the successful use of low-voltage
      scanning electron microscopy (LVSEM) to visualize the glycocalyx in two microbial
      models (Klebsiella pneumoniae and Enterococcus faecalis biofilms) at high
      resolution, and also the dependence on fixation containing polycationic dyes for
      its visualization. Fixation in a paraformaldehyde-glutaraldehyde cocktail without
      cationic dyes was inadequate for visualizing the glycocalyx, whereas addition of
      various dyes (alcian blue, safranin, and ruthenium red) to the aldehyde cocktail
      appeared necessary for stabilization. The cationic dyes varied in size, shape,
      and charge density, and these factors appeared responsible for different
      phenotypic appearances of the glycocalyx with each dye. These results suggest
      that aldehyde fixation with cationic dyes for high-resolution LVSEM will be a
      useful tool for investigation of microbial biofilms as well as investigation of
      the extent and role of the glycocalyx in microbial attachment to surfaces.

PMID- 15505336
TI  - Immunolocalization of caveolin-1 in rat and human mesothelium.
AB  - Flask-shaped vesicles have been described as caveolae in mesothelial cells in a
      number of animal species based on morphological criteria only. Using an antibody
      against caveolin-1, said to be a biochemical marker of caveolae, immunoelectron
      microscopy suggests that many but not all such vesicles in mesothelial cells are
      caveolae. Mesothelial cells from different anatomical sites showed obvious
      variations in both the population density and distribution of these flask-shaped
      vesicles and in their density of immunostaining. Lung and pericardial sac had the
      highest staining density. In some sites (e.g., lung, bladder, colon) caveolae
      were equally distributed between apical and basolateral surfaces, whereas in
      others (e.g., spleen, liver), they were predominantly apical. Additional
      immunopositive sites in the peritoneal membrane were identified, including the
      epineurium of peripheral nerves and the endothelium of lymphatic vessels. We
      further suggest that variations in the number of mesothelial cell caveolae and
      the density of their immunolabeling may have implications for our understanding
      of certain diseases such as malignant mesothelioma, especially in view of the
      recent hypothesis that it may be caused by SV40, a virus that appears to enter
      cells via caveolae.

PMID- 15505338
TI  - Additive and/or synergistic action (downregulation) of androgens and thyroid
      hormones on the cellular distribution and localization of a true tissue
      kallikrein, mK1, in the mouse submandibular gland.
AB  - We investigated the effects of 5alpha-dihydrotestosterone (DHT), 3,5,3'-triiodo-l
      thyronine (T(3)), and dexamethasone (Dex) on the expression of mK1 in the
      granular convoluted tubule (GCT) cells of the submandibular gland (SMG) of
      hypophysectomized (Hypox) male mice by indirect enzyme-labeled antibody and
      immunogold antibody methods for light and electron microscopy. Hypox resulted in
      considerable atrophy of the GCT cells, which were always immunoreactive for mK1,
      and the cells were characterized by apical small dense secretory granules labeled
      with gold particles suggesting the presence of mK1, small Golgi apparatus, sparse
      rough endoplasmic reticulum (RER), and developed basal infoldings. Each of the
      hormones, DHT, T(3), and Dex, enhanced the GCT phenotype to various degrees in
      Hypox male mice. Both DHT alone and T(3) alone moderately inhibited mK1 synthesis
      by increasing the number of mK1-immunonegative GCT cells in Hypox males, but Dex
      alone had no inhibitory effect on mK1 synthesis. A significant trophic effect on
      GCT cells was induced by combined injection of DHT and T(3) or of all three
      hormones, and was reflected in the appearance of abundant large secretory
      granules, well-developed Golgi apparatus and RER, and reduced basal infoldings.
      Only a few such GCT cells were immunopositive for mK1, and the pattern of
      immunopositive and immunonegative cells very closely resembled the mosaic pattern
      seen in normal male GCTs. These findings suggested that the sexual dimorphism of
      mK1 expression and the morphological appearance of GCT cells can be induced by
      treatment with two hormones, DHT and T(3), but not by either of them alone. T(3)
      appears to have a permissive effect on committed GCT cells that results in
      downregulation of mK1 expression in these cells.

PMID- 15505339
TI  - Spatial distribution and initial changes of SSEA-1 and other cell adhesion
      related molecules on mouse embryonic stem cells before and during
      differentiation.
AB  - We examined the distribution of cell adhesion-related molecules (CAMs) among
      mouse embryonic stem (ES) cells and the spatial distribution on cell surfaces
      before and during differentiation. The cell-cell heterogeneity of SSEA-1, PECAM
      1, and ICAM-1 among the undifferentiated cells in the ES cell colonies was
      evident by immunohistochemistry and immuno-SEM, supporting the flow cytometry
      findings. In contrast, most undifferentiated ES cells strongly expressed CD9.
      SSEA-1 was located preferentially on the edge of low protuberances and microvilli
      and formed clusters or linear arrays of 3-20 particles. PECAM-1 and ICAM-1 were
      randomly localized on the free cell surfaces, whereas CD9 was preferentially
      localized on the microvilli or protuberances, especially in the cell periphery.
      Both the SSEA-1(+) fraction and the SSEA-1(-) fraction of magnetic cell sorting
      (MACS) formed undifferentiated colonies after plating. Flow cytometry showed that
      these populations reverted separately again to a culture with a mixed phenotype.
      Differentiation induced by retinoic acid downregulated the expression of all
      CAMs. Immuno-SEM showed decreases of SSEA-1 in the differentiated ES cells,
      although some clustering still remained. Our findings help to elucidate the
      significance of these molecules in ES cell maintenance and differentiation and
      suggest that cell surface antigens may be useful for defining the phenotype of
      undifferentiated and differentiated ES cells.

PMID- 15505340
TI  - Semicarbazide-sensitive amine oxidase in annulo-aortic ectasia disease: relation
      to elastic lamellae-associated proteins.
AB  - Lysyl oxidases (Lox), which are members of the amine oxidase family, are involved
      in the maturation of elastic lamellae and collagen fibers. Modifications of amine
      oxidases in idiopathic annulo-aortic ectasia disease (IAAED) have never been
      investigated. Our aim was to examine the expression of several proteins that
      might interfere with elastic fiber organization in control (n=10) and IAAED
      (n=18) aortic tissues obtained at surgery. Expression of amine oxidases and
      semicarbazide-sensitive amine oxidase (SSAO), and cellular phenotypic markers
      were examined by immunohistopathology and confocal microscopy. The expression of
      these proteins was assessed in relation to clinical and histomorphological
      features of the arterial wall. In control aorta, SSAO staining was expressed
      along elastic lamellae, whereas in aneurysmal areas of IAAED, SSAO was markedly
      decreased, in association with severe disorganization of elastic lamellae. Smooth
      muscle myosin heavy chain was also decreased in IAAED compared with controls,
      indicating smooth muscle cell dedifferentiation. Multiple regression analysis
      showed that elastic lamellar thickness (ELT) was correlated positively with the
      SSAO:elastin ratio and negatively with the Lox:elastin ratio, and that the
      clinical features of IAAED (aneurysm, thoracic aorta diameter, and aortic
      insufficiency) were positively correlated with ELT but not with SSAO. The
      relationship between SSAO expression and ELT suggests that this amine oxidase may
      be involved in elastic fiber organization. However, in advanced IAAED, the
      deficit in SSAO expression could be secondary to the decrease and fragmentation
      of elastic fibers and/or to vascular smooth muscle cell dedifferentiation.

PMID- 15505341
TI  - Tissue-based assay for ornithine decarboxylase to identify patients likely to
      respond to difluoromethylornithine.
AB  - In a previous publication, we showed that a clinical trial of DL-alpha
      difluoromethyl ornithine (DFMO), in combination with PCV (procarbazine, CCNU,
      vincristine) increased survival of patients with anaplastic gliomas (WHO III) but
      not glioblastoma multiforme (WHO IV). We believe that treatment outcome
      (survival) is inversely related to tumor ornithine decarboxylase (ODC) levels. To
      prove this, we needed to develop an assay to quantify ODC levels in formalin
      fixed tumor tissues, which would enable a retrospective study of tumor biopsy
      specimens from the landmark clinical trial. We developed an assay using a
      specific polyclonal antibody coupled to an Alexa fluorescent dye. Transgenic MHC
      ODC mice with differing levels of ODC in heart muscle were used to establish the
      relationship between mean gray-scale intensity and enzymatic ODC activity. We
      found a direct relationship between mean gray-scale intensity of the ODC antibody
      coupled to Alexa 647 dye and enzymatic activity. Preliminary analysis of a human
      glioma tissue array shows that tumor-specific variations in levels of ODC can be
      semiquantitated. We show that mean gray-scale intensity of
      astrocytoma:glioblastoma is 1:6 and of anaplastic astrocytoma:glioblastoma is
      1:4. We also compared the intensity of antibody to Ki67 coupled with
      phycoerythrin simultaneously in cells but failed to see a relationship that
      crossed histologies. We conclude that we can measure levels of ODC in formalin
      fixed tumor tissue using an antibody to ODC coupled to Alexa 647 dye, and this
      will enable us to conduct a future study to correlate survival of patients with
      gliomas of different histologies treated with DFMO to tumor ODC levels.

PMID- 15505342
TI  - Eccentric localization of osteocytes expressing enzymatic activities, protein,
      and mRNA signals for type 5 tartrate-resistant acid phosphatase (TRAP).
AB  - Enzymatic activity of type 5 tartrate-resistant acid phosphatase (TRAP) has been
      regarded as one of the reliable markers for osteoclasts and their precursors. The
      presence of TRAP activity in osteocytes near the bone resorbing surface has also
      been pointed out in some reports. However, the significance of TRAP reactions in
      osteocytes remains controversial and, in fact, there is no agreement as to
      whether the histochemical enzyme reactions in osteocytes represent the TRAP
      enzyme generated by the respective osteocytes or is a mere diffusion artifact of
      the reaction products derived from the nearby osteoclasts. Current histochemical,
      immunohistochemical, and in situ hybridization studies of rat and canine bones
      confirmed TRAP enzyme activity, TRAP immunoreactivity, and the expression of Trap
      mRNA signals in osteocytes located close to the bone-resorbing surface. TRAP/Trap
      positive osteocytes thus identified were confined to the areas no further than
      200 microm from the bone-resorbing surface and showed apparent upregulation of
      TRAP/Trap expression toward the active osteoclasts. Spatial and temporal patterns
      of TRAP/Trap expression in the osteocytes should serve as a valuable parameter
      for further analyses of biological interactions between the osteocytes and the
      osteoclasts associated with bone remodeling.

PMID- 15505343
TI  - Presence and localization of three lactic acid transporters (MCT1, -2, and -4) in
      separated human granulocytes, lymphocytes, and monocytes.
AB  - We fractionated leukocytes from three donors into >90% pure samples of
      granulocytes, lymphocytes, and monocytes and tested them for transcriptional and
      translational expression of three physiologically-proven lactate transporters,
      monocarboxylate transporter 1(MCT1), MCT2, and MCT4, using RT-PCR and affinity
      purified rabbit antibody (Ab) to the C-terminal segment of each human MCT.
      Transcripts of all three MCTs were identified in each leukocyte fraction by RT
      PCR and proven by sequencing of fragments extracted after isolation on agarose
      gels. Transporter protein of the appropriate size was demonstrated for each of
      the monocarboxylate transporters MCTs in lymphocytes and monocytes by Western
      blot, while lower-molecular-weight bands were found in granulocytes and are
      presumed to be degraded forms, because they were blocked by antibody-antigen (Ab
      Ag) preincubation. IHC demonstrated all three MCTs in methanol-fixed droplets of
      all three leukocyte fractions; stain was abolished on omission of the primary Ab.
      Plasmalemmal staining occurred with all MCTs in all leukocyte fractions. Because
      the K(m) for lactate increases approximately fivefold at each step, with
      MCT2<1<4, leukocytes must use the full range of lactate binding to survive in
      acidic and hypoxic environments. Except for MCT4 in lymphocytes, all the MCTs
      also stained leukocyte cytoplasm, often with distinct granularity. Nuclear
      membrane staining was also seen with MCT1 and MCT2, while platelet plasmalemma
      stained only with MCT2.

PMID- 15505344
TI  - Stem-like cells in human hepatoblastoma.
AB  - Hepatoblastoma is a pediatric liver tumor with epithelial components resembling
      embryonal and fetal liver cells. The existence of teratoid hepatoblastoma
      suggests the presence of stem cells in hepatoblastoma. The aim of this study was
      to analyze the expression of stem cell markers in hepatoblastomas. We studied
      specimens from 10 hepatoblastomas. Five of the hepatoblastomas were of epithelial
      and five of mixed type. Immunohistochemistry (IHC) for the stem cell markers
      CD34, Thy1, c-kit, and the hepatic or biliary lineage markers CK-18, OCH, CK-7,
      and CD56 was performed. Double IHC for stem cell and lineage markers was used to
      identify putative liver stem cells. The different markers showed distinct
      distributions on the tumor cells. Cells in atypical ducts were found to express
      simultaneously stem cell markers and hepatocytic or biliary lineage markers.
      Other cells in connective tissue showed c-kit expression, but not hepatic or
      biliary marker expression. The data show the presence of different cell
      populations bearing stem cell markers in human hepatoblastoma. Ductal cells co
      expressing stem cell markers and hepatic lineage markers phenotypically resemble
      hepatic stem-like cells. These findings support the thesis that stem cells play a
      role in the histogenesis of hepatoblastoma.

PMID- 15505346
TI  - Laser microdissection-based analysis of mRNA expression in human coronary
      arteries with intimal thickening.
AB  - Intimal thickening is an early phase of atherosclerosis characterized by
      differentiation of plaque smooth muscle cells (SMCs) from a contractile to a
      synthetic phenotype. We used laser microdissection (LMD) plus real-time RT-PCR to
      quantify mRNAs for calponin-1 and smoothelin, markers of the contractile
      phenotype, and for serum response factor (SRF), a regulator of SMC
      differentiation, in intimal and medial SMCs of human coronary arteries with
      intimal thickening. RNA expression was also analyzed by ISH and protein
      expression was detected by IHC. LMD plus RT-PCR found similar levels of SRF mRNA
      in intimal and medial SMCs, while medial mRNA levels for calponin-1 and
      smoothelin were higher. ISH confirmed that smoothelin mRNA levels in media
      exceeded those in intima, whereas SRF mRNA levels were similar at both sites. For
      calponin-1 and smoothelin, protein levels mirrored respective mRNA levels. By
      contrast, more medial than intimal SRF protein was present. Our results indicate
      that intimal SMCs exhibit a largely synthetic phenotype, perhaps reflecting lower
      intimal levels of SRF protein; ISH and LMD plus real-time RT-PCR provide
      comparable results; as a valuable alternative to ISH, LMD plus RT-PCR allows
      parallel measurement of several transcripts; and tissue gene expression studies
      must measure both protein and mRNA levels.

PMID- 15505345
TI  - Characterization of a monoclonal antibody, HTA28, recognizing a histone H3
      phosphorylation site as a useful marker of M-phase cells.
AB  - Mitosis is a valuable indicator of active tissue proliferation but, other than
      morphological characteristics, there have hitherto been no markers available to
      detect only M-phase cells. However, a newly established monoclonal antibody
      (MAb), HTA28, recognizing histone H3 (H3) harboring phosphoserine 28, allows
      visualization with mitotic chromosomal condensation. In this study we
      investigated the use of HTA28 for immunohistochemical (IHC) detection of M-phase
      cells in the regenerating rat liver after partial hepatectomy (PH). Groups of
      three to five rats were sacrificed at intervals up to 72 hr after PH and
      proliferation was then assessed by IHC staining using HTA28 and other markers.
      The temporal pattern of the HTA28 staining index (SI) was very similar to that
      for the mitotic index (MI), also showing similarities to the bromodeoxyuridine
      (BrdU) labeling index (LI) with a time lag. The HTA28 SI proved to be higher than
      MI at every time point in line with HTA28 immunoreactivity maintained for all
      stages of M-phase. The spatial distribution of HTA28-positive cells corresponded
      with those of other proliferative cell markers. These therefore provide strong
      evidence for the applicability of HTA28 as an M-phase marker. We also showed that
      antigenicity for HTA28 is lost if tissue is not immediately fixed after sampling.

PMID- 15505347
TI  - GLUT2 immunoreactivity in Gomori-positive astrocytes of the hypothalamus.
AB  - A specialized subtype of astrocyte, the Gomori-positive (GP) astrocyte, is
      unusually abundant and prominent in the arcuate nucleus of the hypothalamus. GP
      astrocytes possess cytoplasmic granules derived from degenerating mitochondria.
      GP granules are highly stained by Gomori's chrome alum hematoxylin stain, by the
      Perl's reaction for iron, or by toluidine blue. The source of the oxidative
      stress causing mitochondrial damage in GP astrocytes is uncertain, but such
      damage could arise from the oxidative metabolism of glucose transported into
      astrocytes by high-capacity GLUT2 glucose transporters. In accord with this
      hypothesis, the reported anatomical distribution of astrocytes staining
      positively for GLUT2 glucose transporters closely matches that of GP astrocytes.
      To examine whether or not these two staining procedures detect the same
      population of astrocytes, immunocytochemistry was performed on semithin sections
      to detect GLUT2 protein and sections were then stained with toluidine blue to
      detect GP granules. It was determined that GP astrocytes are frequently
      immunoreactive for the GLUT2 transporter protein. These data support the
      possibility that GP astrocytes may have an important influence upon the
      reactivity of the hypothalamus to glucose and that a specialized glucose
      metabolism may in part underlie the development of mitochondrial abnormalities in
      hypothalamic GP astrocytes.

PMID- 15505348
TI  - Coronary angioplasty reduces free wall rupture and improves mortality and
      morbidity of acute myocardial infarction.
AB  - BACKGROUND: Free wall rupture (FWR) is one of the major causes of mortality in
      acute myocardial infarction (AMI). To what extent coronary angioplasty for AMI
      would modify the predictors of FWR is not clear. METHODS: In prospective database
      of consecutive 3,138 AMI patients seen between May 1985 to May 2002, 3,096
      patients (98.7%) who underwent emergent coronary angiography were analyzed
      retrospectively. The incidence of FWR was determined by univariate and
      multivariate analyses. RESULTS: FWR after admission occurred in 40 (1.3%)
      patients. A higher rate of FWR was associated with: 1) not having coronary
      angioplasty (3.2% vs. 0.9%, p< 0.0001); 2) thrombolytic agents usage (2.4% vs.
      1.0%, p = 0.004); 3) female gender (2.5% vs. 1.1%, p = 0.0004); 4) failed
      reperfusion (5.4% vs. 0.9%, p< 0.0001); and 5) LMT-related infarct (4.7% vs.
      1.2%, p = 0.02) in univariate analysis. Five conditions were identified as
      significant protective or predictive factors of FWR in multivariate logistic
      regression analysis: having coronary angioplasty (odds ratio [OR]: 0.45, 95%
      confidence interval [95% CI] 0.22-0.94, p = 0.03), failed reperfusion (OR: 4.57,
      95% CI: 2.31-9.05, p< 0.0001), LMT-related infarct (OR: 4.96, 95% CI: 1.42-17.34,
      p = 0.01), female gender (OR: 2.17, 95% CI: 1.11-4.25, p = 0.02) and age (OR:
      1.04, 95% CI: 1.00-1.07, p = 0.03). Coronary angioplasty alone resulted in a
      lower incidence of FWR (0.5%) than thrombolysis alone (1.6%, p = 0.02), coronary
      angioplasty with thrombolysis (3.3%, p< 0.0001) and without either treatment
      (6.3%, p< 0.0001). CONCLUSIONS: Angiographic reperfusion success was the most
      significant protective factor from FWR. Coronary angioplasty reduced FWR
      complicating AMI and its concomitant fatality.

PMID- 15505349
TI  - Reducing myocardial free wall rupture following acute ST-segment elevation
      myocardial infarction: a case for primary angioplasty.

PMID- 15505350
TI  - Same-day discharge is preferred by the majority of the patients undergoing radial
      PCI.
AB  - There is limited data on patient preference for same-day discharge PCI. We
      contacted 953 patients who had same-day discharge radial PCI between 1998 and
      2001 and checked whether they were satisfied with same-day discharge and whether
      they had any complications within 30 days post-PCI (vascular, repeat
      angiogram/PCI). Complications and health status were also verified by checking
      hospital records, our province-wide cath lab database and provincial vital
      statistics, as well as by contacting the referring doctor. A total of 811
      patients responded. Of this total, 88.6% of the patients were satisfied with same
      day discharge PCI, and 11.4% were not. Patients were significantly more satisfied
      with same-day discharge when they did not experience vascular complications
      (83.4% versus 91.5% satisfied with and without vascular complications at 24
      hours, and 74.3% versus 90.9% at 30 days, p < 0.01). Patient preference on same
      day discharge was the same regardless of whether they needed a repeat PCI within
      30 days (p > 0.05). Patients for whom early discharge was important were
      significantly more satisfied with same-day discharge (97.9% versus 79.7% when
      early discharge was not important, p < 0.01). Patients who were reluctant to be
      discharged on the same day of the procedure were significantly less satisfied
      compared to those who were not (71.9% vs. 96.4% respectively, p < 0.01). A few
      patients (8.6%) had difficulty finding transportation home and were significantly
      less satisfied (70.0% vs. 90.3% when they found transportation easily, p < 0.01).
      In conclusion, same-day discharge is preferred by the majority of the patients
      undergoing radial PCI.

PMID- 15505351
TI  - My home is my castle.

PMID- 15505352
TI  - Ascending aortic hemodynamics and one-year clinical events following percutaneous
      coronary intervention.
AB  - Increased pulse pressure has been shown to predict mortality and major adverse
      cardiac events (MACE) in large cohorts of ambulatory patients. There have been
      reports suggesting worsened outcome following percutaneous coronary balloon
      angioplasty in patients with increased pulse pressure. We reviewed 434 patients
      undergoing percutaneous coronary stenting to assess for clinical outcomes as a
      function of pulse pressure (PP) and pulse pressure fraction (PPf). At 1 year,
      MACE was identified in 17.9% of subjects. There was no statistically significant
      difference in PP or PPf in those subjects with and without death, myocardial
      infarction or revascularization. Although previously reported to have correlation
      with risk for revascularization following balloon angioplasty, aortic pulse
      pressure at the time of percutaneous coronary intervention with stenting does not
      predict the risk for cardiac events at 1 year.

PMID- 15505353
TI  - Intravascular ultrasound predictors of subacute vessel closure after balloon
      angioplasty or atherectomy.
AB  - BACKGROUND: Factors leading to subacute vessel closure after percutaneous
      coronary intervention (PCI) have not been well established in lesions treated
      with balloon angioplasty or atherectomy. METHODS AND RESULTS: We used
      intravascular ultrasound (IVUS) to determine the pre- and post-PCI
      characteristics involved in subacute vessel closure after PCI. Of 3,403 patients
      undergoing IVUS imaging during coronary balloon angioplasty or atherectomy, 8
      patients (0.2%) developed angiographically documented subacute vessel closure
      within 1 week post-PCI and were compared to a group matched by procedure date
      (within 6 months), age, gender, stable or unstable angina, lesion location and
      treatment (balloon angioplasty or atherectomy). IVUS identified at least one
      cause for subacute vessel closure in 87% of patients (vs 25% in matched lesions,
      p < 0.01). Causes were all procedure-related and included inadequate final lumen
      (60%), dissection (50%) and thrombus (25%). Pre-procedure lesion characteristics
      were not different from matched lesions. CONCLUSIONS: Subacute vessel closure
      after balloon angioplasty or atherectomy is mostly related to insufficient post
      procedure lumen dimension or dissection.

PMID- 15505354
TI  - Modifications of minimal luminal diameter during the 24 hours following
      percutaneous treatment of in-stent restenosis.
AB  - The early renarrowing after percutaneous coronary interventions (PCI) for in
      stent restenosis (ISR) is a phenomenon that has received little investigation.
      Therefore, we assessed the angiographic minimal luminal diameter (MLD) before,
      immediately after, and 24 hours after the procedure in 30 ISR's treated with
      balloon angioplasty (BA) or rotational atherectomy (RA). The MLD was 0.68+/-0.48
      mm at baseline, 2.42+/-0.38 mm after the procedure, and 2.25+/-0.39 mm at 24
      hours (p < 0.0001 for all comparisons). Therefore, a small but significant
      decrease in MLD between post-procedure and 24 hours, corresponding to an early
      loss of 0.18+/-0.16 mm, was evident. The early loss was not significantly
      different in ISR's treated with BA or RA (0.15+/-0.16 mm and 0.20+/-0.16 mm,
      respectively). No significant correlation between early loss and lesion length,
      diameter stenosis, reference diameter, and acute gain was found. However, no
      increase of the 24-hour diameter stenosis to more than 50% was observed. We
      conclude that the magnitude of early luminal loss after PCI of ISR is small and
      therefore does not generally constitute a clinical problem.

PMID- 15505356
TI  - Transcatheter management of platypnea-orthodeoxia syndrome.

PMID- 15505355
TI  - Management of platypnea-orthodeoxia syndrome by transcatheter closure of atrial
      communication: hemodynamic characteristics, clinical and echocardiographic
      outcome.
AB  - Percutaneous transcatheter closure of patent foramen ovale or atrial septal
      defect is an alternative to surgery for the treatment of platypnea-orthodeoxia
      syndrome. We report the hemodynamic characteristics and clinical and
      echocardiographic outcomes of 18 patients with platypnea-orthodeoxia syndrome
      that underwent transcatheter closure of patent foramen ovale or atrial septal
      defect. Successful closure was achieved in all patients with no in-hospital
      mortality or adverse events. Complete resolution of symptoms was seen in all
      patients and mean oxygen saturation increased from 82.6 +/- 5.4% to 96.1+/-2.2%
      post-procedure (p < 0.01).

PMID- 15505357
TI  - Global endovascular or surgical treatment: a challenging case of combined
      coronary artery, abdominal aorta and iliac arteries inflammatory aneurysmal
      disease.

PMID- 15505358
TI  - AngioJet thrombectomy.
AB  - The AngioJet rheolytic thrombectomy system is designed to remove thrombus with
      the Venturi-Bernoulli effect, with multiple high-velocity, high-pressure saline
      jets which are introduced through orifices in the distal tip of the catheter to
      create a localized low-pressure zone, resulting in a vacuum effect with the
      entrainment and dissociation of bulky thrombus. Rheolytic thrombectomy with the
      AngioJet catheter can reduce the thrombus burden in the setting of AMI and
      degenerated SVGs. The long-term follow-up appears to be favorable in patients
      treated with rheolytic thrombectomy in the setting of acute myocardial infarction
      over conventional primary angioplasty.

PMID- 15505359
TI  - The treatment of carotid artery bifurcation stenoses with systematic stenting:
      experience of first 100 consecutive cardiological procedures.
AB  - Carotid endarterectomy still represents the gold standard treatment of carotid
      artery bifurcation stenosis but percutaneous angioplasty with stenting is rapidly
      growing as a non-invasive alternative. In this paper we report the results of
      systematic application of carotid stenting performed in a cardiological setting,
      particularly as regards clinical management of patients and technical approach.
      One-hundred (100) procedures of carotid artery stenting (CAS) on 94 consecutive
      patients, both symptomatic and asymptomatic, with a carotid stenosis > 70%, were
      performed over a period of 30 months. The technical approach was directly derived
      from coronary angioplasty with use of large lumen guiding catheters, 0.014 in.
      intravascular guidewires and distal protection devices usually employed in
      coronary interventions. In 3 cases, a post-carotid endarterectomy restenosis and
      in 97 cases, a de-novo lesion, were treated respectively; in 71 cases, the degree
      of stenosis was 71-89% and in 29 cases, 90-99%. Cerebral protection was obtained
      with a distal to the lesion endovascular filter in 63 cases. Immediate technical
      success, i.e. residual stenosis of the treated vessel < 30% and no significant
      pathologic acceleration of blood flow (< 1.5 m/sec) at the Doppler ultrasound
      evaluation, was achieved in all procedures (100%). Ninety-six (96) procedures
      were totally uncomplicated; in-hospital cerebral complications were 1 TIA, 2
      minor and 1 major strokes; at 30-day follow-up one additional major stroke
      occurred. Despite a particularly high incidence of comorbidities, neither
      unfavorable cardiological complications nor neurologic deaths were reported.
      Systematic CAS is a feasible treatment of the carotid artery bifurcation stenosis
      with high procedural success and low perioperative and short term complications.
      Its performance in a cardiological setting can combine satisfying procedural
      results and potentially successful handling of cardiovascular complications.

PMID- 15505360
TI  - Transradial subclavian and coronary stenting in a single procedure.

PMID- 15505361
TI  - The utility of a steerable long introducer sheath to facilitate left ventricular
      lead placement during a complex biventricular implantable cardioverter
      defibrillator implant.

PMID- 15505362
TI  - Acute myocardial infarction following the use of antimigraine therapy.

PMID- 15505364
TI  - A Palmaz-Schatz stent was partially resected by directional coronary atherectomy
      device to treat a stent-jailed side branch.

PMID- 15505363
TI  - Treatment of post-stenotic saphenous vein graft aneurysm: special considerations
      with the polytetrafluoroethylene-covered stent.
AB  - The use of the polytetrafluoroethylene-covered stents is expanding and its full
      potential in percutaneous coronary intervention is still being defined. The
      synthetic covered stent has been used in the treatment of coronary as well as
      saphenous vein graft disease. In the treatment of relatively large aneurysms of
      saphenous vein grafts, however, the technical and anatomic aspects may be unusual
      and challenging. We present a case of an ostial saphenous vein graft lesion with
      a saccular post-stenotic aneurysm treated with a polytetrafluoroethylene-covered
      stent. Special consideration is made of the procedural technique and the unusual
      anatomic challenge.

PMID- 15505365
TI  - Closure devices are not benign: case closed or artery closed?

PMID- 15505366
TI  - Interaction of Alzheimer's disease amyloid beta peptide fragment 25-35 with tau
      protein, and with a tau peptide containing the microtubule binding domain.
AB  - The interaction of amyloid beta (Abeta) 25-35 with tau protein and with the
      peptide 1/2R (KVTSKCGSLGNIHHKPGGG), has been investigated by chromatography,
      electron microscopy, and surface plasmon resonance (SPR). Abeta 25-35 comprises
      the minimum region of Abeta peptide that is able to aggregate into fibrils, and
      1/2R contains residues 307-325 from the tau region involved in microtubule
      binding. The results of chromatography showed that Abeta 25-35 induces the
      aggregation of tau protein and of tau peptide 1/2R. Likewise, the results of
      electron microscopy showed that Abeta 25-35 increases the tau peptide
      polymerization observed in the presence of polyanions like heparin. A decrease in
      Abeta 25-35 aggregation induced by tau peptide was also observed by both
      techniques. No direct interaction between tau protein immobilized on the sensor
      surface and Abeta 25-35 could be detected by SPR. However, incubation of tau
      protein at room temperature produced the loss of capability of this protein for
      interacting with the active biosensor surface. The presence of Abeta 25-35 during
      the incubation of tau protein makes more efficient this loss of interacting
      capability with the sensor surface. These results clearly indicate that Abeta 25
      35, the peptide region to which the cytotoxic properties of Abeta can be
      assigned, interacts with the peptide region of tau protein involved in
      microtubule binding. This interaction produces the aggregation of tau peptide and
      the concomitant disassembling of Abeta 25-35, offering thus an explanation to the
      lack of co-localization of neurofibrillary tangles and senile plaques in
      Alzheimer's disease, and suggesting the possibility that tau protein may have a
      protective action by preventing Abeta from adopting the cytotoxic, aggregated
      form.

PMID- 15505367
TI  - Absence of heparan sulfate proteoglycans in Lewy bodies and Lewy neurites in
      Parkinson's disease brains.
AB  - alpha-Synuclein is the major constituent of Lewy bodies and Lewy neurites in
      Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Relatively little
      is known about the exact mechanism of alpha-synuclein deposition and
      fibrillization in these alpha-synucleinopathies. In order to better understand
      the pathogenesis of alpha-synucleinopathies it is important to identify molecules
      that regulate the fibrillization of alpha-synuclein. Since it has been
      demonstrated that heparan sulfate proteoglycans (HSPGs) and glycosaminoglycans
      (GAGs) promote the conversion of non-fibrillar amyloid beta-protein (Abeta) into
      neurotoxic fibrillar Abeta in Alzheimer's disease, they might also be involved in
      alpha-synuclein aggregation. It was the aim of our study to examine the
      distribution pattern of these macromolecules in PD brains and the possible
      association with Lewy bodies and Lewy neurites. Although HSPGs clearly
      colocalized with senile plaques, we were unable to identify HSPGs or GAGs in Lewy
      bodies and Lewy neurites and therefore concluded that it is likely that alpha
      synuclein fibrillization and stabilization occurs independently of the presence
      of HSPGs or GAGs.

PMID- 15505368
TI  - Pathological and clinical heterogeneity of presenilin 1 gene mutations.
AB  - The presenilins are two closely related genes which implication in familial
      Alzheimer's disease (FAD) is well known. Presenilin 1 gene (PS1) mutations cause
      heterogeneous disorders and a bibliographical review of atypical PS1-FAD cases
      allows us to describe a great diversity of neuropathological and clinical
      variations and conclude that most of them do not strongly depend on the genetic
      location of the mutation so other genetic or epigenetic factors may be involved.

PMID- 15505369
TI  - Development of a safe oral Abeta vaccine using recombinant adeno-associated virus
      vector for Alzheimer's disease.
AB  - A new oral vaccine for Alzheimer's disease was developed using recombinant adeno
      associated virus vector carrying Abeta cDNA (AAV/Abeta). Oral administration of
      the vaccine without adjuvant induced the expression and secretion of Abeta1-43 or
      Abeta1-21 in the epithelial cell layer of the intestine in amyloid precursor
      protein transgenic mice. Serum antibody levels were elevated for more than six
      months, while T cell proliferative responses to Abeta was not detected. Brain
      Abeta burden was significantly decreased compared to the control without
      inflammatory changes. This oral AAV/Abeta vaccine seems to be promising for
      prevention and treatment of Alzheimer's disease.

PMID- 15505370
TI  - The potential role of tau protein O-glycosylation in Alzheimer's disease.
AB  - Single O-linked N-acetylglucosamine (O-GlcNAc) sugar residues can compete with
      phosphate groups to occupy specific sites on certain nuclear and cytosolic
      proteins. Here we show that inhibiting cellular kinase activities resulted in
      changes in protein O-glycosylation levels in heat-stable cytoskeletal protein
      fractions derived from primary neuronal cells. As increased phosphorylation of
      the microtubule-associated protein tau is one of the pathological hallmarks of
      Alzheimer's disease and glycosylation may play an influential role in this
      process. We observed a significant decrease in the protein O-GlcNAc glycosylation
      of a tau-enriched cytoskeletal fraction generated from AD post-mortem brain
      samples as compared with control, suggesting an inverse relationship between the
      two post-translational modifications. Finally, cells transfected with the cDNA
      coding for O-GlcNAc transferase (OGT) displayed altered tau phosphorylation
      patterns as compared with control cells, suggesting that changes in tau
      glycosylation may influence its phosphorylation state. The specificity of the
      changes in the phosphorylation of individual amino acid residues provides
      evidence for a targeted O-glycosylation of tau.

PMID- 15505371
TI  - Apolipoprotein E genotyping: accurate, simple, high throughput method using ABI
      Prism SNaPshot Multiplex System.
AB  - Apolipoprotein E (apo E) is an essential constituent of several plasma
      lipoproteins, and plays an important role in lipoprotein metabolism. The apo E
      gene exhibits two common functional polymorphisms, producing 3 isoforms known to
      be associated with the risks of developing cardiovascular disease and
      susceptibility to Alzheimer's disease. Numerous different methods have been
      established for determining the three apo E isoforms, yet there are disadvantages
      and ambiguities associated with all of them. We used a method adapted for
      multiplex automated primer extension analysis by improving a commercially
      available protocol (SNaPshot) and simultaneously typing apo E single nucleotide
      polymorphisms (SNPs) encoding for isoforms at codon 112 and 158. This protocol
      relies on the extension with fluorescent dideoxyNTPs of a primer that ends one
      nucleotide 5' of a given SNP (minisequencing). Improvement of the method is
      achieved by incorporating into the minisequencing reaction two pooled primers
      corresponding to both apo E SNPs followed by analysis on an ABI PRISM 310 DNA
      sequencer. We found full concordance with genotypes determined using universal
      heteroduplex. This method is readily available for many laboratories and is a
      simple, unequivocal easy to use technique suitable for large amount of clinical
      samples that may provide a significant improvement over previously reported
      methods for apo E genotyping.

PMID- 15505372
TI  - Reversible dementia: a case of cryptococcal meningitis masquerading as
      Alzheimer's disease.
AB  - A 70-year-old man presented to us in 1994 with a three-year history of worsening
      dementia. With the exceptions of a Mini-Mental State exam score of 20 and an
      inability to tandem walk, his physical and neurological examinations were normal.
      His past medical history revealed that in 1992 he had been evaluated at another
      institution for memory impairment and bifrontal headaches. A spinal tap had been
      done in 1992 showing elevated protein, reduced glucose, and a pleocytosis; his
      CSF fungal culture and cryptococcal antigen test were negative. He subsequently
      was lost to follow-up, and although his headaches had resolved, his mental status
      had continued to worsen. In 1994 his CSF cryptococcal antigen was positive, and
      his CSF fungal culture grew C. neoformans. He gradually improved with treatment
      for cryptococcal meningitis (CM). With the exception of mild memory impairment,
      in 2003 he and his family thought that his mental status had returned to normal.
      This case emphasizes that: 1) CM should always be kept in the differential
      diagnosis of dementia; 2) CM may be extremely insidious and difficult to
      diagnose; and 3) if one is to rule out unequivocally all possible reversible
      causes of dementia, one should perform a spinal tap.

PMID- 15505373
TI  - Apolipoprotein is required for the formation of filamentous amyloid, but not for
      amorphous Abeta deposition, in an AbetaPP/PS double transgenic mouse model of
      Alzheimer's disease.
AB  - To determine the role of apolipoprotein E (apoE) in the deposition of different
      forms of Alzheimer amyloid deposit, we studied mice expressing both mutant human
      amyloid beta-protein precursor (AbetaPP) and presenilin 1 (PS1) that, in
      addition, were either normal or knocked-out for apoE. By 7 months of age,
      extensive deposits of amorphous amyloid beta (Abeta) had developed equally in
      both lines, indicating that, when present in high amounts, Abeta alone is
      sufficient for such deposition to occur. In contrast, filamentous, thioflavine S
      positive amyloid deposition in AbetaPP/PS mice was catalyzed at least 3000 fold
      by apoE. Electron micrographs further illustrated the filamentous nature of Abeta
      deposits in mice expressing apoE. These and other behavior data indicate that the
      primary function of apoE in Alzheimer's disease is to promote the polymerization
      of Abeta into mature, beta pleated sheet filaments, a process that is necessary
      for inducing cognitive decline. Thus, preventing apoE from binding to Abeta may
      prove to be an effective means of therapeutic intervention.

PMID- 15505374
TI  - Rodent Abeta(1-42) exhibits oxidative stress properties similar to those of human
      Abeta(1-42): Implications for proposed mechanisms of toxicity.
AB  - Alzheimer's disease is a neurodegenerative disorder associated with aging and
      cognitive decline. Amyloid beta peptide (1-42) [Abeta(1-42)] is a primary
      constituent of senile plaques - a hallmark of Alzheimer's disease - and has been
      implicated in the pathogenesis of the disease. Previous studies have shown that
      methionine residue 35 of beta(1-42) may play a critical role in Abeta(1-42)
      mediated oxidative stress and neurotoxicity. Several additional mechanisms of
      neurotoxicity have been proposed, including the role of Cu(II) binding and
      reduction to produce hydrogen peroxide and the role of peptide aggregation. It
      has been reported that rodent Abeta is less likely to form larger beta-sheet
      structures, and consequently, large aggregates. As a consequence of the lack of
      deposition of the peptide in rodent brain, rodent Abeta has been proposed to be
      non-toxic. Additionally, the sequence of the rodent variety of Abeta(1-42)
      contains three amino acid substitutions compared to the human sequence. These
      substitutions include the shift of arginine 5, trysosine 10, and histidine 13 to
      glycine, phenylalanine, and arginine, respectively. This shift in sequence within
      the Cu(II) binding region of the peptide results in a decrease in the ability of
      the rodent Abeta peptide to reduce Cu(II) to Cu(I) compared to the human Abeta
      peptide. As a result of the effect of the amino acid variations on the ability of
      the rodent peptide to reduce Cu(II) to Cu(I) compared to the human peptide, the
      rodent beta has been proposed to lack oxidative stress properties. In this study,
      the oxidative stress and neurotoxic properties of rodent beta(1-42) [Abeta(1
      42)Rat] were evaluated and compared to those of human Abeta(1-42). Both human
      Abeta(1-42) and beta(1-42)Rat were found to have a significant effect on neuronal
      DNA fragmentation, loss of neuritic networks, and cell viability. beta(1-42) Rat
      was found to cause a significant increase in both protein oxidation and lipid
      peroxidation, similar to Abeta(1-42), both of which were inhibited by the lipid
      soluble, chain breaking antioxidant vitamin E, suggesting that reactive oxygen
      species play a role in the Abeta-mediated toxicity. Taken together, these results
      suggest that Cu(II) reduction may not play a critical role inbeta(1-42)Rat
      induced oxidative stress, and that the oxidative stress exhibited by this peptide
      may be a consequence of the presence of methionine 35, similar to the findings
      associated with the native human beta(1-42) peptide.

PMID- 15505375
TI  - Thyrotropin releasing hormone inhibits tau phosphorylation by dual signaling
      pathways in hippocampal neurons.
AB  - Depletion of thyrotropin releasing hormone (TRH) gene expression resulted in
      augmented tau and glycosynthetase kinase-3beta (GSK-3beta), in contrast, TRH
      administration resulted in decreases of 75% in GSK-3beta and 90% in Tau
      phosphorylation in cultured rat hippocampal neurons. To further study TRH
      regulation of tau phosphorylation, immunoblotting was used to explore G-protein
      coupled TRH receptor activation of the phosphokinase C (PKC) and phosphokinase A
      (PKA) signaling pathways. TRH was found to rapidly activate PKA (2.5 fold in 10
      min) while it suppressed PKC (levels decreased by 85% vs. control) in hippocampal
      neurons. This process was also discovered to be a cell type-specific response, as
      TRH activated PKC in only hypothalamic neurons. Further investigation revealed
      that the Src inhibitor Protein Phosphatase 2 (PP2, 50 uM) could block TRH
      inhibition of PKC, GSK-3beta, and tau phosphorylation with no effects on PKA. In
      addition, the PKC inhibitor GF109203 Bis (10 uM) was also able to suppress TRH
      inhibition of GSK-3beta, leading to increased GSK-3 beta activity. Independent of
      these effects, inhibition of PKA by H89 (10 uM) significantly blocked TRH
      inhibition of GSK-3 beta. These data suggests that both PKA and PKC are
      independently crucial to TRH's effects on GSK-3 beta, and support the roles of
      two distinct pathways involving suppression of PKC via the Src kinase and
      activation of PKA in mediating TRH effects on GSK-3 beta and tau. These dual
      signaling pathways between TRH and tau may provide mechanisms for the precise
      regulation of tau phosphorylation and dephosphorylation in neurons.

PMID- 15505376
TI  - Maternal Phenylketonuria Collaborative Study (MPKUCS)--the 'outliers'.
AB  - Analysis of outcome data from 305 of the 414 offspring from the Maternal
      Phenylketonuria Collaborative Study (MPKUCS), plus 70 control offspring, revealed
      significant deficits in the IQ (intelligence quotient), as measured by the
      Wechsler Intelligence Scale for Children--Revised (WISC-R), when maternal
      metabolic control during pregnancy was delayed and/or inadequate. There were,
      however, 23 'outliers' (7.5% of the 305) in which the offspring's intellectual IQ
      was worse (n =10) or better (n =13) than expected. The aim of this study was to
      determine whether collection parameters were incomplete or whether these subjects
      were true biological variants influenced by other undetected factors or, perhaps,
      by modifier genes. Among the 10 offspring whose intellectual functioning was
      worse than expected, additional complications were uncovered that could explain
      the poor outcome. Four of the 13 offspring with higher than expected IQ had
      mothers with mild variants of PKU in which the insult to the fetus would not be
      expected to be as profound. For the other nine offspring whose intellectual
      performance was better than expected, there was no explanation, based on the
      parameters studied. We hypothesize that modifier genes will, at times, protect
      the fetus despite high maternal concentrations of phenylalanine. Not all
      offspring from the same (untreated) PKU mother may be similarly affected. Finding
      the source of these modifiers might effect the treatment of MPKU.

PMID- 15505377
TI  - NPT4, a new microsomal phosphate transporter: mutation analysis in glycogen
      storage disease type Ic.
AB  - Deficiency of a microsomal phosphate transporter in the liver has been suggested
      in some patients affected by glycogen storage disease type Ic (GSD Ic). Several
      Na(+)/phosphate co-transporters have been characterized as members of the anion
      cation symporter family. Recently, the cDNA sequence of two phosphate
      transporters, NPT3 and NPT4, expressed in liver, kidney and intestine, has been
      determined. We studied expression of human NPT4 in COS cells and observed an ER
      localization of the transporter by immunofluorescence microscopy. We speculated
      that this transporter could play a role in the regulation of the glucose-6
      phosphatase (G6-Pase) complex. We revealed the genomic structure of NPT4 and
      analysed the gene as a candidate for GSD Ic. DNA was collected from five patients
      without mutations in G6-Pase or the G6-P transporter gene. DNA analysis of NPT4
      revealed that one patient was heterozygous for a G>A transition at nucleotide 601
      which would result in a G201R substitution. Our results do not confirm the
      hypothesis that this gene is mutated in GSD Ic patients. However, we cannot
      exclude that the mutation found reduces the phosphate transport efficiency,
      possibly modulating the G6-Pase complex.

PMID- 15505378
TI  - Congenital cardiomyopathy and pulmonary hypertension: another fatal variant of
      cytochrome-c oxidase deficiency.
AB  - Biventricular hypertrophy was noted at 24 weeks' gestation in a fetus with
      isolated cytochrome-c oxidase (COX) deficiency. Shock, caused by hypertrophic
      cardiomyopathy and severe pulmonary hypertension, led to the patient's death on
      day 6. His phenotype defines a new lethal variant of COX deficiency characterized
      by prenatal-onset cardiopulmonary pathophysiology.

PMID- 15505379
TI  - Isobutyryl-CoA dehydrogenase deficiency: isobutyrylglycinuria and ACAD8 gene
      mutations in two infants.
AB  - Isobutyryl-CoA dehydrogenase (IBD) is an enzyme involved in the catabolism of the
      branched-chain amino acid valine. We report a third and a fourth child with IBD
      deficiency who were both detected during newborn screening with tandem mass
      spectrometry and so far do not receive any treatment. The diagnosis was confirmed
      by biochemical and molecular studies. One of the children is homozygous for the
      mutation M128I in the ACAD8 gene, which is predicted to affect the substrate
      binding cavity. The other child is compound heterozygous for a frameshift
      mutation F33fsins and a missense mutation V203I. It is as yet uncertain whether
      IBD deficiency may cause significant morbidity in affected children and whether
      treatment is necessary. In view of the limited experience worldwide, careful
      monitoring of the children is recommended.

PMID- 15505380
TI  - Assessing the severity of the small inframe deletion mutation in the alpha
      subunit of beta-hexosaminidase A found in the Turkish population by reproducing
      it in the more stable beta-subunit.
AB  - GM(2) gangliosidoses are a group of panethnic lysosomal storage diseases in which
      GM(2) ganglioside accumulates in the lysosome due to a defect in one of three
      genes, two of which encode the alpha- or beta-subunits of beta- N 
      acetylhexosaminidase (Hex) A. A small inframe deletion mutation in the catalytic
      domain of the alpha-subunit of Hex has been found in five Turkish patients with
      infantile Tay-Sachs disease. To date it has not been detected in other
      populations and is the only mutation to be found in exon 10. It results in
      detectable levels of inactive alpha-protein in its precursor form. Because the
      alpha- and beta-subunits share 60% sequence identity, the Hex A and Hex B genes
      are believed to have arisen from a common ancestral gene. Thus the subunits must
      share very similar three-dimensional structures with conserved functional
      domains. Hex B, the beta-subunit homodimer is more stable than the heterodimeric
      Hex A, and much more stable than Hex S, the alpha homodimer. Thus, mutations that
      completely destabilize the alpha-subunit can often be partially rescued if
      expressed in the aligned positions in the beta-subunit. To better understand the
      severity of the Turkish HEXA mutation, we reproduced the 12 bp deletion mutation
      (1267-1278) in the beta-subunit cDNA. Western blot analysis of permanently
      transfected CHO cells expressing the mutant detected only the pro-form of the
      beta-subunit coupled with a total lack of detectable Hex B activity. These data
      indicate that the deletion of the four amino acids severely affects the folding
      of even the more stable beta-subunit, causing its retention in the endoplasmic
      reticulum and ultimate degradation.

PMID- 15505382
TI  - Molecular basis of hypoxanthine-guanine phosphoribosyltransferase deficiency in
      Italian Lesch-Nyhan patients: identification of nine novel mutations.
AB  - Lesch-Nyhan syndrome (LSN, McKusick 300322) is an X-linked genetic disease due,
      in its typical form, to the complete absence of hypoxanthine-guanine
      phosphoribosyltransferase (HPRT, EC 2.4.2.8) enzyme activity. It is characterized
      by hyperuricaemia, leading to gout and kidney stones, accompanied by severe
      neurological dysfunction with self-injurious behaviour, choreoathetosis and
      spasticity. Based on a worldwide birth incidence estimate of about 1:380000, one
      or two new cases are expected every year in Italy. We performed biochemical and
      molecular genetic studies on 28 Italian patients from 25 families who are likely
      to represent most living individuals with the syndrome in the country. They all
      had absent HPRT activity and a typical LNS phenotype. Genetic analysis identified
      24 HPRT mutations, 9 of which had not been previously reported: 74C>G (P25R),
      IVS2+1G>C, 194-195delTC, 329-332delCAAC insTCTs, IVS9-1G>A, 506insC, IVS8-1G>C,
      606G>T (L202F), 418G>C (G140R). No mutation hotspots were identified. Only two
      mutations were found in more than one family, indicating the lack of any major
      mutation causing LNS in Italy. Three mutations arose de novo , two in the
      proband's mother, one in the maternal grandmother. The virtual complete absence
      of HPRT activity was related to deletions, nonsense, or missense mutations
      leading to nonconservative amino acid changes.

PMID- 15505381
TI  - Sustained therapeutic effects of oral miglustat (Zavesca, N
      butyldeoxynojirimycin, OGT 918) in type I Gaucher disease.
AB  - It has been shown that treatment with miglustat (Zavesca, N
      butyldeoxynojirimycin, OGT 918) improves key clinical features of type I Gaucher
      disease after 1 year of treatment. This study reports longer-term efficacy and
      safety data. Patients who had completed 12 months of treatment with open-label
      miglustat (100-300 mg three times daily) were enrolled to continue with therapy
      in an extension study. Data are presented up to month 36. Liver and spleen
      volumes measured by CT or MRI were scheduled every 6 months. Biochemical and
      haematological parameters, including chitotriosidase activity (a sensitive marker
      of Gaucher disease activity) were monitored every 3 months. Safety data were also
      collected every 3 months. Eighteen of 22 eligible patients at four centres
      entered the extension phase and 14 of these completed 36 months of treatment with
      miglustat. After 36 months, there were statistically significant improvements in
      all major efficacy endpoints. Liver and spleen organ volumes were reduced by 18%
      and 30%, respectively. In patients whose haemoglobin value had been below 11.5
      g/dl at baseline, mean haemoglobin increased progressively from baseline by 0.55
      g/dl at month 12 (NS), 1.28 g/dl at month 24 (p =0.007), and 1.30 g/dl at month
      36 (p =0.013). The mean platelet count at month 36 increased from baseline by 22
      x 10(9)/L. No new cases of peripheral neuropathy occurred since previously
      reported. Diarrhoea and weight loss, which were frequently reported during the
      initial 12-month study, decreased in magnitude and prevalence during the second
      and third years. Patients treated with miglustat for 3 years show significant
      improvements in organ volumes and haematological parameters. In conclusion,
      miglustat was increasingly effective over time and showed acceptable tolerability
      in patients who continued with treatment for 3 years.

PMID- 15505383
TI  - The 3rd International Workshop on glutaryl-CoA delhydrogenase deficiency.

PMID- 15505384
TI  - Development of pathogenic concepts in glutaryl-CoA dehydrogenase deficiency: the
      challenge.
AB  - The purpose of this review is to set the stage for discussions that follow about
      the biochemical and molecular bases of glutaric acidaemia type I, and about the
      pathogenesis of the characteristic acute striatal necrosis that often occurs
      during the first years of life.

PMID- 15505385
TI  - Excitotoxicity and bioenergetics in glutaryl-CoA dehydrogenase deficiency.
AB  - Glutaryl-CoA dehydrogenase deficiency is an inherited organic acid disorder with
      predominantly neurological presentation. The biochemical hallmark of this disease
      is an accumulation and enhanced urinary excretion of two key organic acids,
      glutaric acid and 3-hydroxyglutaric acid. If untreated, acute striatal damage is
      often precipitated by febrile illnesses during a vulnerable period of brain
      development in infancy or early childhood, resulting in a dystonic dyskinetic
      movement disorder. 3-hydroxyglutaric and glutaric acids are structurally similar
      to glutamate, the main excitatory amino acid of the human brain, and are
      considered to play an important role in the pathophysiology of this disease. 3
      hydroxyglutaric acid induces excitotoxic cell damage specifically via activation
      of N-methyl-D-aspartate receptors. It has also been suggested that secondary
      amplification loops potentiate the neurotoxic properties of these organic acids.
      Probable mechanisms for this effect include cytokine-stimulated NO production, a
      decrease in energy metabolism, and reduction of cellular creatine phosphate
      levels. Finally, maturation-dependent changes in the expression of neuronal
      glutamate receptors may affect the vulnerability of the immature brain to
      excitotoxic cell damage in this disease.

PMID- 15505386
TI  - Animal models for glutaryl-CoA dehydrogenase deficiency.
AB  - In vitro studies suggest that excitotoxic cell damage is an underlying mechanism
      for the acute striatal damage in glutaryl-CoA dehydrogenase (GCDH) deficiency. It
      is believed to result from an imbalance of glutamatergic and GABAergic
      neurotransmission induced by the accumulating organic acids 3-hydroxyglutaric
      acid (3-OH-GA) and to a lesser extent glutaric acid (GA). Stereotaxic
      administration of 3-OH-GA and GA into the rat striatum have confirmed these
      results, but may not truly represent the effect of chronic exposure to these
      compounds. In an attempt to better understand the pathophysiology of GCDH
      deficiency in vivo , two animal models have been utilized. A mouse that lacks
      GCDH activity in all tissues was generated by gene targeting in embryonic stem
      cells. These animals develop the characteristic biochemical phenotype of the
      human disease. Pathologically, these mice have a diffuse spongiform myelinopathy
      similar to that in human patients; however, there is no evidence for acute
      striatal damage or sensitivity to acute encephalopathy induced by catabolism or
      inflammatory cytokines. A naturally occurring animal model, the fruit-eating bat
      Rousettus aegypticus, lacks hepatic and renal GCDH activity, but retains cerebral
      enzyme activity. Like the mouse, these bats develop the characteristic
      biochemical phenotype of glutaryl-CoA dehydrogenase deficiency, but lack overt
      neurological symptoms such as dystonia. It is not known whether they also develop
      the spongiform myelinopathy seen in the Gcdh-deficient mice. Otherwise, these
      constellations would suggest that cerebral GCDH deficiency is responsible for the
      development of neuronal damage. The lack of striatal damage in these two rodent
      models may also be related to species differences. However, they also highlight
      our lack of a comprehensive understanding of additional factors that might
      modulate the susceptibiliy of neurons to accumulating 3-OH-GA and GA in GCDH
      deficiency. Unravelling these mechanisms may be the key to understanding the
      pathophysiology of this unique disease and to the development of neuroprotective
      strategies.

PMID- 15505387
TI  - Preliminary attempts to establish a rat model of striatal injury in glutaric
      acidaemia type I.
AB  - Glutaric acidaemia type I (GA I) is caused by the deficiency of glutaryl-CoA
      dehydrogenase, resulting in accumulation of glutaric acid (GA) and 3-
      hydroxyglutaric acid (3-OH-GA) in blood and cerebrospinal fluid (CSF).
      Neuropathological changes with onset in childhood consist of severe neuronal loss
      in the caudate and putamen. An animal model is necessary to test possible
      intervention strategies, and prior reports suggested that GA or 3-OH-GA could be
      used to create specific neuron loss in adult rats. Adult, 3-week-old and 2-week
      old rats received intrastriatal injections of GA and 3-OH-GA at a range of doses.
      High concentrations caused necrotic lesions in striatum. Low concentrations
      caused white-matter axonal damage and small areas of neuron loss. Injection of
      lipopolysaccharide prior to administration of 3-OH-GA was not associated with
      enhanced neuronal loss. Our findings contradict prior claims and we conclude that
      the simple model of a single GA or 3-OH-GA injection into rat brain does not
      replicate the neuropathological findings in humans.

PMID- 15505388
TI  - Modulation of glutamatergic and GABAergic neurotransmission in glutaryl-CoA
      dehydrogenase deficiency.
AB  - Although the precise mechanisms underlying the CNS degeneration of patients with
      glutaryl-CoA dehydrogenase (GCDH) deficiency are still the subject of intense
      debate, many studies have highlighted that excitotoxicity plays a fundamental
      role in the neuropathology of this disease, particularly involving the N-methyl-D
      aspartate receptor subtype of ionotropic glutamate receptors. Modulation of the
      glutamatergic system by these compounds involves an inhibition of glutamate
      uptake into synaptosomes and synaptic vesicles, and a decrease in glutamate
      binding. Furthermore, glutaric and 3-hydroxyglutaric acids inhibit glutamate
      decarboxylase, the key enzyme of GABA synthesis, and striatal GABAergic medium
      spiny neurons are highly vulnerable to 3-hydroxyglutaric acid-induced
      neurotoxicity. In conclusion, glutaric acid and 3-hydroxyglutaric acid induce an
      imbalance in glutamatergic and GABAergic neurotransmission.

PMID- 15505389
TI  - Vascular dysfunction as an additional pathomechanism in glutaric aciduria type I.
AB  - The metabolic hallmark of glutaric aciduria type I (GA I) is the deficiency of
      glutaryl-CoA dehydrogenase (GCDH) with subsequent accumulation of glutaric acid,
      3-hydroxglutaric acid (3-OH-GA) and glutaconic acid. Current concepts regarding
      pathomechanisms of GA I focus on investigations of excitotoxic effects of 3-OH
      GA. To identify pathogenetically relevant genes, microarray analyses were
      performed using brain material from GCDH-deficient (GCDH (-/-)) and control mice.
      These microarray data confirmed recent pathogenic models, but also revealed
      alterations in genes that had previously not been correlated to the disease, e.g.
      genes concerning vascular biology. Subsequent in vitro and in vivo experiments
      confirmed direct effects of 3-OH-GA on vascular permeability and endothelial
      integrity. Clinical observations underscore the involvement of vascular
      dysfunction. In MRI scans of GA I patients, subdural effusions as well as dilated
      transarachnoid vascular plexuses were detected independently of encephalopathic
      crises. In fact, some of these findings are already detectable shortly after
      birth. MRI scans of a GA I patient performed during an acute encephalopathic
      crisis detected a dilated intrastriatal vasculature with perivascular
      hyperintensity, indicating local extravasation. In conclusion, we hypothesize
      that 3-OH-GA affects prenatal development of vessels, thus leading to an
      increased vulnerability of endothelial structures and subsequent vascular
      dysfunction. These observations display an additional pathomechanism in GA I and
      might explain frontotemporal hypoplasia and chronic subdural effusions in this
      disease. Elucidation of the pathomechanisms of vascular dysfunction may give
      further insights into the pathogenesis of GA I.

PMID- 15505390
TI  - Glutaric aciduria type I and kynurenine pathway metabolites: a modified
      hypothesis.
AB  - Glutaric aciduria type I is an inborn error of organic acid metabolism that
      demonstrates a particular temporal vulnerability (acute encephalopathic episodes
      in infancy) and a spatial vulnerability (acute striatal necrosis, focused on the
      putamen). Excitotoxic mechanisms involving 3-hydroxyglutaric acid as the major
      neurotoxin have been suggested. This paper proposes a role for metabolites of the
      kynurenine pathway in the pathogenic process and modifies the hypothesis of
      Heyes. Deficiency of glutaryl-CoA dehydrogenase blocking the glutarate pathway
      and activation of indoleamine 2,3-dioxygenase in macrophages/monocytes by
      intercurrent inflammation may increase flux down the kynurenine pathway towards
      the production of quinolinic acid. Quinolinic acid is neurotoxic and is an
      endogenous agonist at N-methyl-D-aspartate receptors. Synergistic excitation of
      these receptors by quinolinic acid and 3-hydroxyglutaric acid, which alone does
      not have sufficient potency, may be involved in the pathogenesis of striatal
      necrosis.

PMID- 15505392
TI  - Neonatal screening for glutaryl-CoA dehydrogenase deficiency.
AB  - Acute encephalopathic crisis in glutaryl-CoA dehydrogenase deficiency results in
      an unfavourable disease course and poor outcome, dominated by dystonia, feeding
      problems, seizures and secondary complications, and quite often leading to early
      death. The prerequisite for the prevention of irreversible brain damage in this
      disease is the detection of affected patients and initiation of treatment before
      the manifestation of such crisis. Apart from macrocephaly there are no signs or
      symptoms characteristic for this disease in presymptomatic children and, thus,
      they are usually missed. In some countries, implementation of extended neonatal
      screening programmes using electrospray ionization tandem mass spectrometry (ESI
      MS/MS) allows detection of affected newborns and start of therapy before onset of
      neurological complications. This article summarizes recent strategies, pitfalls
      and shortcomings of a mass screening for glutaryl-CoA dehydrogenase deficiency
      using ESI-MS/MS. Furthermore, an alternative strategy, namely DNA-based neonatal
      screening for the Oji-Cree variant of this disease, is demonstrated. An
      optimization of diagnostic as well as therapeutic procedures must be achieved
      before GCDH deficiency unequivocally fulfills the criteria of a reliable and
      successful newborn screening programme.

PMID- 15505391
TI  - Challenges for basic research in glutaryl-CoA dehydrogenase deficiency.
AB  - During the last decades, efforts have been made to elucidate the complex
      mechanisms underlying neuronal damage in glutaryl-CoA dehydrogenase deficiency. A
      combination of in vitro and in vivo investigations have facilitated the
      development of several hypotheses, including the probable pathogenic role of
      accumulating glutaric acid and 3-hydroxyglutaric acid. However, there are still
      many shortcomings that limit an evidence-based approach to treating this inborn
      error of metabolism. Major future goals should include generation of a suitable
      animal model for acute striatal necrosis, investigation of the formation,
      distribution and exact intra- and extracellular concentrations of accumulating
      metabolites, a deeper understanding of striatal vulnerability, and systematic
      investigation of effects on cerebral gene expression during development and of
      the modulatory role of inflammatory cytokines.

PMID- 15505393
TI  - Correlation of genotype and phenotype in glutaryl-CoA dehydrogenase deficiency.
AB  - We have investigated the correlation between genotype and phenotype in a large
      number of patients with glutaric aciduria type I (GA I). The deficiency of
      glutaryl-CoA dehydrogenase has been confirmed in the Rigshospitalet's laboratory
      in 215 patients since 1975. Most of the patients were of European ancestry.
      Complete absence of enzyme activity was found in more than half of the patients,
      while 34% of patients had a residual activity up to 5% and a few patients had a
      residual activity of 5-15%. In four exceptional cases, a very high residual
      activity of up to 30% was found. Enzyme studies are thus a reliable method for
      confirming the diagnosis of GA I, although it may be difficult to distinguish
      exceptional 'mild' cases from heterozygous carriers for GA I. Three of the
      patients with very high residual activity are compound heterozygous for the
      missense mutations R227P and V400M, both of which are associated with residual
      enzyme activity of 8-10% in homozygous patients. Patients with a mild mutation on
      at least one chromosome frequently show unusual biochemical findings such as low
      or normal urinary excretion of glutaric acid and mild or only slightly increased
      excretion of 3-hydroxyglutaric acid. In contrast, patients with severe mutations
      such as R402W or A293T on both alleles have no residual activity and show the
      typical urinary metabolite pattern. Clinical data were available for a subgroup
      of 79 patients. No correlation with the biochemical phenotype or the genotype
      could be established.

PMID- 15505394
TI  - Neuroradiological findings in glutaric aciduria type I (glutaryl-CoA
      dehydrogenase deficiency).
AB  - This article summarizes the magnetic resonance imaging features of glutaric
      aciduria type I (GA I) based on the cases presented at the 3rd International
      Workshop on Glutaryl-CoA Dehydrogenase Deficiency together with a review of
      previously reported neuroimaging characteristics of GA I. Previous reports have
      focused on characteristic findings, such as basal ganglia injury and
      frontotemporal atrophy or hypoplasia, subdural effusions and white-matter
      disease. Most of these findings have been demonstrated in symptomatic children,
      i.e. after manifestation of acute encephalopathic crises. In contrast,
      prospective investigations in presymptomatically diagnosed children are rare.
      Since more recent investigations have highlighted CNS changes in patients without
      encephalopathic crises, systematic prospective investigations of
      neuroradiological findings in this disease are indispensable for a better
      understanding of this disease. Based on these findings a suggestion for a MRI
      protocol is presented, supporting a standardized evaluation of patients with GA
      I.

PMID- 15505395
TI  - Nuclear magnetic resonance spectroscopy in glutaryl-CoA dehydrogenase deficiency.
AB  - Nuclear magnetic resonance (NMR) spectroscopy is a safe, noninvasive method that
      is the preferred technique for in vivo analysis of specific chemical compounds in
      localized brain regions. Besides quantification of compounds, NMR spectroscopy
      allows the detailed analysis of neurotransmitter, glucose and lactate metabolism
      following peripheral infusions of stable isotopically labelled precursors. The
      latter has been successfully applied to patients with different neurological
      disease states not including glutaryl-CoA dehydrogenase (GCDH) deficiency. In
      contrast, single patients with GCDH deficiency who were neurologically
      unremarkable have been studied with conflicting results. One patient was shown to
      have an increase in intracerebral creatine and phosphocreatine concentrations,
      while the second studied had unremarkable levels. In a 15-year-old patient, we
      were able to demonstrate elevated levels of intracerebral lactate and elevated
      choline/N -acetylaspartate ratios, indicating potentially increased myelin
      turnover and reduced neuronal integrity in periventricular white matter.
      Interestingly, spectra in basal ganglia were within normal limits. Systematic
      studies to address well-defined questions in GCDH deficiency are urgently needed.
      In particular, analysis of in vivo neurotransmitter metabolism following
      administration of isotopically labelled precursors in patients with GCDH
      deficiency, both when metabolically stable and when unstable, may help to advance
      our understanding of the pathophysiology of GCDH deficiency.

PMID- 15505397
TI  - Emergency treatment in glutaryl-CoA dehydrogenase deficiency.
AB  - The history of glutaryl-CoA dehydrogenase deficiency is determined by acute
      encephalopathic crises that are precipitated by common febrile diseases,
      vaccinations or surgical interventions during infancy and early childhood. Such
      crises result in an irreversible destruction of the basal ganglia (in particular
      of the putamina), and consequently dystonia, dyskinesia and choreoathetosis.
      Secondary complications include feeding and speech problems, failure to thrive,
      recurrent aspiration, immobilization, severe motor deficits and early death. It
      is generally accepted that maintenance treatment based on dietary lysine or
      protein restriction and supplementation with carnitine (and riboflavin) is
      insufficient to prevent acute crises during intercurrent illnesses or conditions
      that enhance catabolic state. Consequently, outpatient and inpatient emergency
      therapies have been implemented. The present review describes a recommended
      approach to emergency therapy for this disease.

PMID- 15505396
TI  - Maintenance treatment of glutaryl-CoA dehydrogenase deficiency.
AB  - This paper summarizes the published experience as well as results of the 3rd
      International Workshop on Glutaryl-CoA Dehydrogenase Deficiency held in October
      2003 in Heidelberg, Germany, on the topic treatment of patients with glutaryl-CoA
      dehydrogenase (GCDH) deficiency. So far no international recommendation for
      treatment of GCDH deficiency exists. Such an approach is hampered by several
      facts, namely the lack of an in-depth understanding of the pathophysiology of the
      disease, the lack of prospective studies, including the evaluation of drug
      monotherapy, and lack of objective documentation of clinical changes (e.g. video
      documentation) during pharmacotherapy.

PMID- 15505398
TI  - Reduction of lysine intake while avoiding malnutrition--major goals and major
      problems in dietary treatment of glutaryl-CoA dehydrogenase deficiency.
AB  - Treatment in glutaryl-CoA dehydrogenase deficiency, an inborn error of metabolism
      of lysine and tryptophan, is mainly based on restriction of lysine intake,
      supplementation of carnitine, and an intensification of therapy during
      intercurrent illnesses. The major principle of dietary treatment is to reduce the
      production of glutaric acid and 3-hydroxyglutaric acid by restriction of natural
      protein in general and of lysine in particular. In parallel to development, the
      growing child learns to utilize different protein sources, shifting the primarily
      milk-based diet to a mixed diet. The changes in nutritional demands and food
      composition during the first years of life greatly influence nutritional support
      for affected patients at different ages. This article highlights frequent
      pitfalls of dietary treatment for this disease and focuses on particular risks of
      malnutrition in terms of essential amino acids and micronutrients and/or excess
      intake of lysine between age 3 months and age 6 years. We conclude from the
      examples given that restriction of natural protein intake plus application of
      lysine-free amino acid mixtures minimizes the risk of malnutrition and allows a
      reliable control of protein and lysine intake and, thus, seems particularly
      recommendable during the vulnerable period for acute encephalopathic crises. The
      efficacy of these theoretical and experience-based approaches to dietary
      treatment of glutaryl-CoA dehydrogenase deficiency should be investigated in
      detail in prospective clinical studies.

PMID- 15505399
TI  - Management of movement disorders in glutaryl-CoA dehydrogenase deficiency:
      anticholinergic drugs and botulinum toxin as additional therapeutic options.
AB  - Glutaric aciduria type I is an inborn error of metabolism due to the deficiency
      of glutaryl-CoA dehydrogenase, an enzyme responsible for the catabolism of
      lysine, hydroxylysine and tryptophan. The most important neurological symptoms
      include dyskinesia and dystonia, which can be focal, segmental or generalized.
      Treatment of the extrapyramidal syndrome is often unsatisfactory. We report our
      experience in the treatment of generalized and focal dystonia with
      anticholinergic drugs and botulinum toxin type A, respectively. Both therapies
      proved beneficial.

PMID- 15505400
TI  - Glutaric aciduria type I: outcome in the Republic of Ireland.
AB  - Twenty-one patients have been diagnosed with glutaric aciduria type I over a 16
      year period in the Republic of Ireland, 11 following clinical presentation and 10
      following a high-risk screen. Nineteen have been managed with diet. Eight
      patients have died, of whom 7 were diagnosed clinically. Six had dystonic and one
      spastic cerebral palsy. Of the 11 patients who did not have cerebral palsy, 10
      were diagnosed following a high-risk screen. Seven of the 11 have no abnormal
      neurological signs; 6 of the 7 have abnormal CT or MRI findings; and no case of
      striatal degeneration has occurred during the past 14 years in the high-risk
      screened group.

PMID- 15505401
TI  - Looking forward--an evidence-based approach to glutaryl-CoA dehydrogenase
      deficiency.
AB  - Three decades after the first description of glutaryl-CoA dehydrogenase
      deficiency, major progress has been achieved in the prevention of acute striatal
      necrosis and neurological sequelae in affected children, if diagnosis is made
      early and treatment is started before manifestation of acute encephalopathic
      crises. However, all concepts for diagnostic work-up, monitoring, and treatment
      are solely experience-based, and 10-35% of early-diagnosed children do not or
      only incompletely benefit from the current management. They still develop
      neurological deterioration and sequelae despite early implementation of dietary
      treatment, carnitine supplementation and emergency treatment during acute
      intercurrent illnesses. International efforts should be made to move management
      of affected children from experience-based to evidence-based medicine. Major
      tools for this optimization are the establishment of an international patients'
      database, the implementation of an international prospective clinical study, and
      the development of international guidelines for diagnostic work-up, monitoring
      and therapy.

PMID- 15505402
TI  - Evidence for chromosome and Pst I satellite DNA family evolutionary stasis in the
      Bufo viridis group (Amphibia, Anura).
AB  - The West Palearctic green toads, Bufo viridis , represent a species complex.
      Apart from tetraploid populations, which form at least one separate species,
      evidence exists for relevant differentiation among diploid populations. We
      present the results of a chromosomal (C-, Ag-NOR-, Replication pattern, DAPI and
      CMA3 banding) and molecular study (isolation and characterization of a satellite
      DNA family) carried out on a number of Central Asian, European and North African
      populations. For comparative purposes, our molecular analysis was also extended
      to specimens of three additional Bufo species (B. bufo, B. mauritanicus and B.
      cf. regularis ), as well as two rare African bufonids (Werneria mertensis and
      Wolterstoffina sp.). Our results demonstrate a remarkable karyological and
      molecular evolutionary stasis in the Bufo viridis complex. In fact, all
      chromatinic markers showed the same pattern and/or composition in all specimens,
      independently of their origin and ploidy levels. Even the NOR loci were
      invariably two and located on the telomeric regions of two chromosomes of the
      sixth pair, or quartet. Furthermore, very similar patterns of genomic
      hybridization of a monomeric unit of the Pst I satellite DNA family (named pBv)
      were observed in all diploid and tetraploid populations, as well as in B. bufo
      and B. mauritanicus . Finally, pBv hybridizes with monomeric units of Pst I
      satellite DNA in all species studied, including Werneria and Wolterstorffina,
      which are thought to have separated from Bufo as early as in the Mesozoic.

PMID- 15505403
TI  - Conservation of aphidicolin-induced fragile sites in Papionini (Primates) species
      and humans.
AB  - Fragile sites are considered structural features of mammalian chromosomes and a
      commonly repeated hypothesis is that they are evolutionarily conserved. We tested
      this hypothesis by establishing the subchromosomal homology of regions harbouring
      fragile sites in the chromosomes of humans, Macaca fascicularis (MFA) and
      Mandrillus sphinx (MSP). We delineated the interspecific homology of chromosome
      bands expressing aphidicolin-induced fragile sites of homologues to human
      chromosomes 1, 3, 5, 7, 18 and X by the comparative FISH of human BAC and YAC
      clones. Notably, two YAC clones known to span human chromosome regions containing
      fragile sites were shown to also span fragile sites in macaques and mandrills.
      The present comparative BAC/YAC mapping data represent, up to now, the most
      precise evidence of fragile site conservation during primate evolution.

PMID- 15505404
TI  - Chromosome painting comparison of Leontopithecus chrysomelas (Callitrichine,
      Platyrrhini) with man and its phylogenetic position.
AB  - Using human probes of whole chromosomes, the homoeologies between human and
      Leontopithecus chrysomelas (Platyrrhini) karyotypes were established. Thirty
      three conserved segments were observed between the two species. Intrachromosomal
      rearrangements between the two species were identified using hybridization of
      chromosome arm probes of human chromosomes 1 and 3. We also used chromosomal data
      to investigate phylogenetic relationships of Callitrichines. These data were
      encoded using Cebus capucinus , a species which kept fairly ancestral
      chromosomes, as reference. Two equi-parsimonious trees, including reversion or
      convergence events, were obtained. The monophyly of Callitrichines is confirmed.
      They share nine chromosomal rearrangements at least. The Cebuella-Callithrix
      group forms a clade sharing five rearrangements at least. According to the tree
      considered, the Tamarins, Leontopithecus and Saguinus share two chromosomal
      rearrangements restricted to these two taxa or none. Callimico accumulated seven
      chromosomal rearrangements unshared with other taxa, at least. To avoid
      convergence and reversion events, we propose the hypothesis of a network (or
      populational) evolution. Six chromosomal rearrangements would have occurred
      during the period of this network evolution. Finally, the karyotype of the last
      common ancestor to all Callitrichines has been reconstructed. It possessed 48
      chromosomes.

PMID- 15505405
TI  - Characterization of the genes encoding for MAD2 homologues in wheat.
AB  - MAD2 (mitotic arrest deficient 2) is a highly conserved protein involving in
      spindle checkpoint control. MAD2 locates at spindle-unattached kinetochores
      during prophase and dissolves from spindle-attached kinetochores towards
      metaphase. In this study, we isolated homologous genes encoding for MAD2 from
      hexaploid wheat. The three homoeologous genes on the long arms of the group-2
      chromosomes shared approximately 99% similarity of the nucleotide sequence in
      coding regions. The intron-exon structures of the three homoeologues were also
      conserved, showing high similarities to that of the Arabidopsis MAD2 gene. All
      three homoeologues were transcribed in roots and spikes but not in leaves. We
      generated antibodies against the polypeptides with amino acid sequences derived
      from the cDNA sequences of the wheat MAD2 homologues. Using these antibodies, we
      found MAD2 in wheat root-tip cells to change in location and amount through the
      cell cycle, similar to those reported for human MAD2. Intense immunostaining
      signals were observed at the centromeres of all metaphase chromosomes when root
      tips were treated with colchicine, a microtubule-destabilizing drug, but no
      signals were observed in untreated chromosomes. Thus, the wheat MAD2 protein
      could be a good marker for the functional kinetochores of metaphase chromosomes
      in wheat.

PMID- 15505406
TI  - High chromosome conservation detected by comparative chromosome painting in
      chicken, pigeon and passerine birds.
AB  - Chicken chromosome paints for macrochromosomes 1-10, Z, and the nine largest
      microchromosomes (Griffin et al. 1999) were used to analyze chromosome homologies
      between chicken (Gallus gallus domesticus: Galliformes), domestic pigeon (Columba
      livia: Columbiformes), chaffinch (Fringilla coelebs Passeriformes), and redwing
      (Turdus iliacus: Passeriformes). High conservation of syntenies was revealed. In
      general, both macro- and microchromosomes in these birds showed very low levels
      of interchromosomal rearrangements. Only two cases of rearrangements were found.
      Chicken chromosome 1 corresponds to chromosome 1 in pigeon, but to chromosomes 3
      and 4 in chaffinch and chromosomes 2 and 5 in redwing. Chicken chromosome 4 was
      shown to be homologous to two pairs of chromosomes in the karyotypes of pigeon
      and both passerine species. Comparative analysis of chromosome painting data and
      the results of FISH with (TTAGGG)n probe did not reveal any correlation between
      the distribution of interstitial telomere sites (ITSs) and chromosome
      rearrangements in pigeon, chaffinch and redwing. In chaffinch, ITSs were found to
      co-localize with a tandem repeat GS (Liangouzov et al. 2002), monomers of which
      contain an internal TTAGGG motif.

PMID- 15505407
TI  - Identification of the homologue of the bovine Rob(1;29) in a captive gaur (Bos
      gaurus).
AB  - Robertsonian translocations have been well documented in domestic cattle, with
      the most commonly occurring fusion involving chromosomes 1 and 29. The widespread
      nature of this translocation is indicative of its ancient origin. The gaur (Bos
      gaurus) is one of many wild cattle species currently listed as vulnerable or
      endangered. Due to the small founder stock and 50 years of restricted breeding,
      the captive herd is showing signs of inbreeding and reduced fertility. Recent
      cytogenetic analysis of a female gaur at Toronto Zoo found that the individual
      contained 2n=57 chromosomes instead of the normal 2n=58, with an extra
      submetacentric and the loss of two acrocentric chromosomes being observed. This
      study was undertaken to identify the translocation in this individual and to
      examine the karyotype of immediate family members. Chromosome analysis of
      fibroblast cell cultures was carried out using GTG-banding, C-banding and FISH
      (bovine 1 and 29 paints) techniques to characterize the translocation. Results
      from the GTG-banding and FISH analyses confirm that the two autosomes involved in
      the translocation are the bovine homologues 1 and 29. A monocentric centromere
      was observed by C-banding. Chromosome abnormalities have not been detected in
      other gaur tested to date. This study demonstrates the importance of cytogenetic
      analysis for the establishment of screening protocols for the assessment of
      reproductive potential in this and other exotic bovinae.

PMID- 15505408
TI  - Holocentric chromosomes in meiosis. I. Restriction of the number of chiasmata in
      bivalents.
AB  - The number of chiasmata in bivalents and the behaviour of chiasmata during the
      meiotic divisions were studied in Psylla foersteri (Psylloidea, Homoptera). Two
      chiasmata with a frequency of 97% and one or three chiasmata with frequencies of
      2% and 0.9%, respectively, were observed in the largest bivalent in male meiosis.
      Meiosis was normal for the largest bivalents with one or two chiasmata, whereas
      bivalents with three chiasmata were not capable of completing anaphase I because
      of their inability to resolve the chiasma located in the middle. Consequently,
      the bivalent was seen as a laggard joining together two metaphase II daughter
      plates. Apparently, cells of this kind are eliminated. Inability to resolve the
      chiasma situated in the middle is attributed to the condensation process, which
      is unable to change the spatial orientation of successive chiasma loops in
      holocentric bivalents so that chiasma loops would be arranged perpendicular to
      each other at metaphase I. Thus they retain their parallel orientation from
      diplotene to metaphase I. Consequently, sister chromatid cohesion is exposed for
      release only in the outermost chiasmata but the chiasma in the middle continues
      to interlock the chromosomes in the bivalent. The elimination of the cells
      carrying bivalents with more than two chiasmata creates a strong selection
      against the formation of more than two chiasmata in holocentric bivalents.

PMID- 15505409
TI  - Comprehensive search for chicken W chromosome-linked genes expressed in early
      female embryos from the female-minus-male subtracted cDNA macroarray.
AB  - In order to seek chicken W chromosome-linked genes expressed significantly
      earlier than the time of gonadal differentiation, female-minus-male-subtracted
      cDNA macroarrays were prepared from day 2 (Hamburger-Hamilton stages 12-13), day
      3 (stages 19-20) and day 4 (stages 24-25) embryos. From a total of 15-744
      macroarrayed cDNA clones, 610 clones exhibiting significantly female-specific
      expression were selected. When each one of the 610 cDNA clones was used as a
      probe in Southern blot hybridization with male or female chicken genomic DNA, 62
      clones, grouped into eight (A-H) types according to their patterns of
      hybridization, were considered to be derived from W chromosome-linked genes. When
      representative cDNA clones in each type were sequenced, clones derived from two
      known W-linked genes; SPIN-W and ATP5A1W , and from two hitherto unknown W-linked
      genes, represented by 2d-2D9 and 2d-2F9 clones, were identified and their
      localizations on the W chromosome were confirmed by fluorescence in-situ
      hybridization. The 2d-2D9 sequence has no significant homology with other genes
      in databases but 2d-2F9 has a region which shows partial homology to the
      consensus sequence of the AAA ATPase superfamily. Both 2d-2D9 and 2d-2F9
      sequences are found in contigs of undetermined chromosome-linkage in the Draft
      Chicken Genome Sequence.

PMID- 15505410
TI  - PI3K-Akt pathway: its functions and alterations in human cancer.
AB  - Phosphatidylinositol-3-kinase (PI3K) is a lipid kinase and generates
      phosphatidylinositol-3,4,5-trisphosphate (PI(3, 4, 5)P3). PI(3, 4, 5)P3 is a
      second messenger essential for the translocation of Akt to the plasma membrane
      where it is phosphorylated and activated by phosphoinositide-dependent kinase
      (PDK) 1 and PDK2. Activation of Akt plays a pivotal role in fundamental cellular
      functions such as cell proliferation and survival by phosphorylating a variety of
      substrates. In recent years, it has been reported that alterations to the PI3K
      Akt signaling pathway are frequent in human cancer. Constitutive activation of
      the PI3K-Akt pathway occurs due to amplification of the PIK3C gene encoding PI3K
      or the Akt gene, or as a result of mutations in components of the pathway, for
      example PTEN (phosphatase and tensin homologue deleted on chromosome 10), which
      inhibit the activation of Akt. Several small molecules designed to specifically
      target PI3K-Akt have been developed, and induced cell cycle arrest or apoptosis
      in human cancer cells in vitro and in vivo . Moreover, the combination of an
      inhibitor with various cytotoxic agents enhances the anti-tumor efficacy.
      Therefore, specific inhibition of the activation of Akt may be a valid approach
      to treating human malignancies and overcoming the resistance of cancer cells to
      radiation or chemotherapy.

PMID- 15505411
TI  - Ranking the role of RANK ligand in apoptosis.
AB  - Many members of tumor necrosis factor (TNF) superfamily are characterized by
      their ability to induce apoptosis once they bind in a homotrimeric manner to
      their cognate receptors. The receptor activator of nuclear factor-kappaB ligand
      (RANKL), a member of the TNF superfamily identified seven years ago, was
      originally described as a factor that induced osteoclastogenesis and dendritic
      cell survival. Recent observations indicate that a growth inhibitory and
      apoptosis-inducing activity is associated with RANKL, as is the case for other
      members of TNF superfamily. This review describes the possible mechanisms of
      induction of RANKL-induced growth inhibition/apoptosis and discusses the role of
      various components in RANKL-signaling in this phenomenon, including TNF receptor
      associated factor (TRAF)-6, nuclear factor-kappaB (NF-kappaB), c-jun N-terminal
      kinase JNK), phosphatidylinositol-3 kinase (PI3K).

PMID- 15505412
TI  - Apoptosome dysfunction in human cancer.
AB  - Apoptosis is a cell suicide mechanism that enables organisms to control cell
      number and eliminate cells that threaten survival. The apoptotic cascade can be
      triggered through two major pathways. Extracellular signals such as members of
      the tumor necrosis factor (TNF) family can activate the receptor-mediated
      extrinsic pathway. Alternatively, stress signals such as DNA damage, hypoxia, and
      loss of survival signals may trigger the mitochondrial intrinsic pathway. In the
      latter, mitochondrial damage results in cytochrome c release and formation of the
      apoptosome, a multimeric protein complex containing Apaf-1, cytochrome c , and
      caspase-9. Once bound to the apoptosome, caspase-9 is activated, and subsequently
      triggers a cascade of effector caspase activation and proteolysis, leading to
      apoptotic cell death. Recent efforts have led to the identification of multiple
      factors that modulate apoptosome formation and function. Alterations in the
      expression and/or function of these factors may contribute to the pathogenesis of
      cancer and resistance of tumor cells to chemotherapy or radiation. In this review
      we discuss how disruption of normal apoptosome formation and function may lead or
      contribute to tumor development and progression.

PMID- 15505413
TI  - The inhibitor of apoptosis protein family and its antagonists in acute leukemias.
AB  - The Inhibitor of Apoptosis Protein family (IAP) functions as inhibitors of
      apoptotic pathways, both death receptor- and mitochondrial mediated. We detail
      the current body of knowledge for the IAP family with regard to their structure
      and function, their expression in normal and leukemic cells, and their prognostic
      importance in acute leukemia. Although there is some evidence that IAPs play an
      important role in the chemoresistance of leukemia cell lines, little is known
      about their influence on this phenomenon in acute leukemia cells of human origin.
      IAPs are also explored as a specific target for new antitumor strategies,
      including antisense oligonucleotides of XIAP (X-chromosome-linked IAP) or
      survivin and small molecules of polyphenylurea-based XIAP inhibitors. Several
      proteins negatively regulate the function of the IAP family. One of those
      antagonists is Smac/DIABLO. Short peptides of Smac were found to enhanced
      apoptosis, induced by chemo- or immunotherapy, in the leukemic cells in vitro.
      Moreover, small-molecule agents, resembling Smac/DIABLO in function, were shown
      to potentiate cytotoxicity of chemotherapy in different malignancies. IAPs,
      exhibiting downstream influence on both external and intrinsic pathways as well
      as on some caspase-independent mechanisms of apoptosis, are potentially
      attractive target for anti-tumor therapy, although their role in the pathology
      and prognosis of acute leukemia has to be further elucidated.

PMID- 15505414
TI  - Anti-apoptotic role of STAT5 in haematopoietic cells and in the pathogenesis of
      malignancies.
AB  - Signal Transducers and Activators of Transcription (STATs) are a family of
      proteins that mediate cytokine and growth factor induced signals playing a role
      in cell differentiation, proliferation, development, inflammation, and apoptosis.
      While other STATs can mediate pro-apoptotic or anti-apoptotic signals depending
      on the conditions of cell stimulation, STAT5 only demonstrates a pro-survival
      signal. The STAT5 induced cell survival promotion is due to regulation of
      transcription of genes that encode proteins which inhibit or trigger the cell
      death, such as the Bcl-2 family members or caspases. STAT5 is essential but not
      sufficient in the survival process. Signalling activators such as Ras and PI3
      Kinase, cooperate with STAT5. Constitutive activation of STAT5 is associated with
      a wide variety of human malignancies, including leukaemia, breast, head and neck,
      and prostate cancers. Up-regulation of STAT5 target genes leads to changes of
      normal cellular growth and survival control mechanisms. Block of constitutive
      STAT5 activation could be a novel therapeutic approach to treat human
      malignancies.

PMID- 15505415
TI  - Proteinase-activated receptor 1 (PAR-1) and cell apoptosis.
AB  - This review summarizes the main aspects and newest findings of how proteinase
      activated receptor 1 (PAR-1) may modulate programmed cell death. Activation of
      PAR-1 has been found to induce or inhibit apoptosis in a variety of cells,
      depending on the dosage of its physiological agonist thrombin, or that of
      synthetic receptor activators. To date, cellular targets for PAR-1-mediated
      effects on apoptosis include neuronal, endothelial, and epithelial cells,
      fibroblasts, and tumor cells. The signaling pathways involved in the induction or
      prevention of apoptosis by PAR-1 activation are diverse, and include JAK/STAT,
      RhoA, myosin light chain kinase, ERK1/2, and various Bcl-2 family members. In
      view of the well-established involvement of microbial proteinases in host tissue
      malfunction, the article also elaborates on the possible significance of PAR-1
      activation for the pathogenesis of infectious disease.

PMID- 15505416
TI  - Differential regulation of caspase-3 by pharmacological and developmental stimuli
      as demonstrated using humanised caspase-3 mice.
AB  - Caspase-3 is a potential therapeutic target for a number of degenerative
      diseases. However the development of specific caspase-3 inhibitors has been
      hampered by inter-species differences and the high degree of homology shared by
      different caspases. To circumvent these issues, we have produced and
      characterised a humanised caspase-3 mouse line (possessing one copy of the human
      gene with both copies of the murine gene disrupted) by crossing human caspase-3
      transgenic mice with nullizygous caspase-3 knock-out mice. Humanised mice
      appeared normal and survived to adulthood. Analysis of the human gene revealed
      that human pro-caspase-3 was expressed in the same tissues as its murine
      counterpart. However humanised mice retained the hypercellularity of frontal
      cortex seen in their knock-out parental line and there was no biochemical
      evidence of human protein processing during naturally occurring neuronal death
      taking place during brain development. In contrast, the human protein was cleaved
      by the mouse machinery following anti-Fas treatment of adult mice. These data
      suggest that there is a fundamental difference between the activation pathways
      leading to caspase-3 cleavage during naturally occurring cell death in
      development/embryogenesis and following an apoptotic stimulus in the adult.

PMID- 15505417
TI  - Apoptosis induced kinetic changes in autofluorescence of cultured HL60 cells
      possible application for single cell analysis on chip.
AB  - INTRODUCTION: This paper presents a new method using natural cellular
      fluorescence (autofluorescence, AF) to study apoptosis. Measurement of AF reduces
      sample preparation time and avoids cellular toxicity due to the fact that no
      labelling is required. METHODS: Human promyelocytic leukemic HL60 cells were
      incubated with camptothecin (CPT), tumour necrosis factor (TNF)-alpha in
      combination with cycloheximide (CHX), or irradiated with 6 or 10 Gray, during
      varying time periods, to initiate apoptosis. AF was measured at the flow
      cytometer. RESULTS: Induction of apoptosis results in the shrinkage of the cell
      and the fragmentation into apoptotic bodies. With flow cytometry, 4
      subpopulations, viable, early apoptotic, late apoptotic and the necrotic cells,
      can be distinguished. Induction of apoptosis results in a decrease in AF
      intensity compared to untreated HL60 cells, especially seen in the late apoptotic
      subpopulation. The AF intensity is found to decrease significantly in time
      (between 2 h and 24 h) for all the four apoptotic inducers used. CONCLUSIONS: Our
      results show that it is possible to specifically measure the apoptotic-induced
      kinetic changes in AF in HL60 cells. A decrease in AF intensity is seen from 2 h
      till 24 h. These results open a door for future developments in single-cell
      analysis.

PMID- 15505418
TI  - Effects of antioxidants on X-ray- or hyperthermia-induced apoptosis in human
      lymphoma U937 cells.
AB  - Hydroxyl radicals (.OH) and superoxide anion radicals (O2.-) are known to play
      cardinal roles in cell killing and various types of cell damage. In order to
      elucidate the mechanism of the involvement of both free radicals on apoptosis,
      the correlation between anti-apoptotic effects and free radical scavenging
      abilities of anti-oxidants was studied. As an indicator of anti-apoptotic
      effects, C1/2 (antioxidant concentration to inhibit DNA fragmentation by 50%) was
      evaluated in human lymphoma cell line U937 cells 6 hr after X-ray (10 Gy) or
      hyperthermia (44 degrees C, 30 min) treatment. Rate constants of the reactions
      between antioxidants and .OH or O2.- were calculated as the scavenging ability of
      the antioxidants with graded concentration estimated by EPR spectroscopy. No
      apparent correlation between C1/2 obtained in apoptosis induced by X-rays or
      hyperthermia and the rate constants of antioxidants for .OH or O2.- was observed.
      On the other hand, the partition coefficients in 1-octanol/water of the
      antioxidants, an indicator of hydrophobicity, revealed a correlation with the
      C1/2 of the agents with hyperthermia, but not with X-ray irradiation. These
      results indicate that the prevention of apoptosis by an antioxidant is not simply
      associated with its scavenging ability for .OH or O2.-. The hydrophobicity of the
      antioxidant, among other possible factors, is involved in the inhibition of
      hyperthermia- induced apoptosis.

PMID- 15505419
TI  - Gamma irradiation-induced apoptosis in murine pre-B cells prevents the
      condensation of fibrillar chromatin in early S phase.
AB  - Local changes in chromatin structure leading to temporally distinct geometric
      forms were characterized in nuclei of reversibly permeabilized cells. Reversal of
      permeabilization was tested by 3H-thymidine incorporation and trypan blue dye
      exclusion. Apoptotic changes were visualized in a cell cycle dependent manner at
      the chromatin level by fluorescent microscopy in non-irradiated cells and after
      400 rad Co60 irradiation. Fluorescent microscopy of chromatin structures
      belonging mainly to the interphase of the cell cycle confirmed the existence of
      specific geometric forms in nuclei of non-irradiated cells. In this control
      population, the following main transitory forms of condensing chromatin were
      distinguished: decondensed veil-like structures and fibrous structures in early
      and mid S phase (2.0-2.5 average C-value), chromatin bodies, semicircles later in
      mid S phase (3.0-3.5 C), precondensed chromosomes in late S (3.5-3.7 C) and
      metaphase chromosomes at the end and after S phase (3.7-4.0 C). Our results show
      that upon gamma-irradiation (a) the cellular and nuclear sizes were increased,
      (b) the DNA content was lower in each elutriated subpopulation of cells, (c) the
      progression of the cell cycle was arrested in the early S phase at 2.4 C value,
      (d) the chromatin condensation was blocked between the fibrillar chromatin and
      precondensed elongated chromosomal forms, and (e) the number and size of
      apoptotic bodies were inversely correlated with the progression of the cell
      cycle, with many small apoptotic bodies in early S phase and less and larger
      apoptotic bodies in late S phase.

PMID- 15505420
TI  - Role of insulin in the anti-apoptotic effect of glucose-insulin-potassium in
      rabbits with acute myocardial ischemia and reperfusion.
AB  - OBJECTIVE: To study the effects of glucose-insulin-potassium (GIK) cocktail on
      cardiac myocyte apoptosis and cardiac functional recovery following myocardial
      ischemia/reperfusion (MI/R), and to further determine the role of insulin in the
      GIK-induced cardioprotective effect in vivo . METHODS: Forty eight male rabbits
      were subjected to 40 min MI followed by R for 3 h and were randomly received one
      of the following treatments: saline, GIK (glucose: 150 g/L, insulin: 60 U/L and
      KCl: 80 mmol/L), or insulin (n = 16 in each group) at 1 ml x kg(-1) x h(-1),
      beginning 30 min before MI and continuing throughout the 3 h-reperfusion. Blood
      glucose, electrolytes, arterial blood pressure and left ventricular pressure
      (LVP) were monitored throughout the experiment. Plasma creatine kinase (CK) and
      lactate dehydrogenase (LDH) activity were measured spectrophotometrically.
      Myocardial infarction and myocardial apoptosis (both DNA laddering and TUNEL
      analysis) were determined in a blinded manner. RESULTS: MI/R caused significant
      cardiac dysfunction and myocardial apoptosis (both strong DNA ladder formation
      and TUNEL-positive staining). Compared with vehicle, GIK-treated rabbits showed
      protection against MI/R as evidenced by reduced myocardial infarction (19.7% +/-
      2.6% vs . 26.8% +/- 3.3% of vehicle, n = 10, P < 0.05), marked decrease in DNA
      fragmentation and apoptotic index (11.0% +/- 2.1% vs . 20.1% +/- 3.1% of vehicle,
      n = 6, P < 0.01), significant decrease of plasma CK and LDH and improved recovery
      of cardiac systolic/diastolic function at the end of R. Treatment with insulin
      alone decreased blood glucose significantly but still exerted cardioprotective
      effects comparable with that of GIK. CONCLUSIONS: GIK exerts cardioprotective
      effects against postischemic myocardial injury and improves cardiac functional
      recovery in vivo . Insulin, mainly through the anti-apoptotic effect, plays a key
      role in the GIK-elicited myocardial protection in MI/R.

PMID- 15505421
TI  - Peloruside A enhances apoptosis in H-ras-transformed cells and is cytotoxic to
      proliferating T cells.
AB  - Peloruside A (peloruside), a compound isolated from the marine sponge Mycale
      hentscheli , inhibits growth of human (HL-60) and mouse (32D-ras) myeloid
      leukemic cells, as well as non-transformed 32D cells. Using the MTT cell
      proliferation assay and trypan blue dye exclusion tests, little difference was
      seen in growth inhibition between 32D and 32D- ras cells; however, peloruside was
      more cytotoxic to the oncogene-transformed cells. Peloruside also blocked 32D-
      ras cells more readily in G2/M of the cell cycle, leading to apoptosis. Annexin
      V/propidium iodide staining of 32D and 32D- ras cells showed that 1.6 microM
      peloruside induced significant cell death by 36 hours in 32D cells (16%
      survival), but to comparable levels as early as 14 hours in 32D- ras cells (11%
      survival). There was no evidence for activation of either of the initiator
      caspases-8 or -9 by 0.1 microM peloruside following 12 hours of exposure.
      Peloruside inhibited T cell proliferation and IL-2 and IFN gamma production in
      both the mixed lymphocyte reaction and following CD3 cross-linking, and this
      effect was shown to be a non-specific cytotoxic effect. It is concluded that
      peloruside preferentially targets oncogene-transformed cells over non-transformed
      cells by inducing transformed cells to undergo apoptosis.

PMID- 15505423
TI  - Role of apoptosis in functional luteolysis in the pregnant rabbit corpus luteum:
      evidence of a role for placental-derived factors in promoting luteal cell
      survival.
AB  - Corpora lutea (CL) were isolated from one rabbit ovary on days 4, 8, 16 (peak
      luteal function), 28 (functional regression) and 30 of pregnancy and processed
      for biochemical analysis of DNA integrity. Analysis of DNA integrity revealed the
      presence of oligonucleosomal fragments in day 28 and day 30 CL but not in day 16
      CL. The extent of low molecular weight (<15 kb) DNA labeling was 6.6 +/- 0.84
      fold higher in day 30 as compared to day 16 CL (mean +/- SEM; n = 4, P < 0.01).
      In a second series of experiments, healthy CL collected from day 16 pregnant
      rabbits were incubated for 2 h in the absence or presence of 250 microg/ml of
      placental extract (PE) obtained from day 16 and/or day 30 placentas. Analysis of
      DNA integrity revealed that extensive apoptosis occurred in CL incubated in
      medium alone and in medium containing day 30 PE. In contrast, day 16 PE
      significantly suppressed apoptosis vs control (70 +/- 4%). In a third series of
      experiments, expression of mRNA for bcl-x and bax was measured by Northern
      analysis of CL treated without and with day 16 PE using cRNA probes for bcl-x and
      bax developed in our laboratory by RT-PCR. Treatment with PE significantly
      reduced bax mRNA levels but did not change bcl-x mRNA levels. These studies
      provide evidence that functional luteolysis in the pregnant rabbit CL is
      correlated with the occurrence of apoptosis. The data suggest that a factor(s)
      derived from the placenta may be responsible for the prolongation of CL life span
      during pregnancy by its ability to alter the bax:bcl -x rheostat and suppress
      apoptosis.

PMID- 15505422
TI  - Bcl-2 and CCND1/CDK4 expression levels predict the cellular effects of mTOR
      inhibitors in human ovarian carcinoma.
AB  - Molecular markers enabling the prediction of sensitivity/resistance to rapamycin
      may facilitate further clinical development of rapamycin and its derivatives as
      anticancer agents. In this study, several human ovarian cancer cell lines
      (IGROV1, OVCAR-3, A2780, SK-OV-3) were evaluated for susceptibility to rapamycin
      mediated growth inhibition. The differential expression profiles of genes coding
      for proteins known to be involved in the mTOR signaling pathway, cell cycle
      control and apoptosis were studied before and after drug exposure by RT-PCR. In
      cells exposed to rapamycin, we observed a dose-dependent downregulation of CCND1
      (cyclin D1) and CDK4 gene expression and late G1 cell cycle arrest. Among these
      cell lines, SK-OV-3 cells resistant to both rapamycin and RAD001 were the sole to
      show the expression of the anti-apoptotic gene Bcl-2. Bcl-2/bclxL-specific
      antisense oligonucleotides restored the sensitivity of SK-OV-3 cells to apoptosis
      induction by rapamycin and RAD001. These results indicate that baseline Bcl-2
      expression and therapy-induced downexpression of CCND1 and CDK4 may be regarded
      as molecular markers enabling the prediction and follow-up of the cellular
      effects on cell cycle and apoptosis induction of rapamycin in ovarian cancer.
      Furthermore, strategies to down regulate Bcl-2 in ovarian cancer may prove useful
      in combination with rapamycin or RAD001 for ovarian cancer.

PMID- 15505424
TI  - Activation of multidomain and BH3-only pro-apoptotic Bcl-2 family members in p53
      defective cells.
AB  - In the p53-deficient human B lymphoma Namalwa cell line that quickly undergoes
      apoptosis after DNA topoisomerase I inhibitor (camptothecin, CPT) treatment, we
      observed rapid and slight induction of the pro-apoptotic BH3-only Bik, Bim-EL,
      Bim-L and Bim-S proteins. In contrast, the expression levels of Bad and
      multidomain Bax-alpha and Bak remained mostly unchanged after CPT treatment.
      However, multiple pro-apoptotic proteins, including Bax-alpha, Bak, Bik, Bim-EL
      and Bim-L, translocated rapidly to the mitochondria after CPT treatment. Gel
      filtration chromatography experiments demonstrated that somes of the pro
      apoptotic proteins assemble themselves into high molecular weight protein
      complexes. The protein composition of these oligomers was further analyzed by co
      immunoprecipitation experiments performed on highly purified mitochondrial
      fractions, which revealed the formation of Bax/Bak, Bax/VDAC1, Bak/VDAC1,
      Bim/VDAC1 and Bim/Bcl-2 complexes after DNA damage induction. Thus, it appeared
      that induction, mitochondrial translocation and assembly in multimeric protein
      complexes of several pro-apoptotic members of the Bcl-2 family correlated with
      the rapid activation of apoptosis in a p53-independent pathway after CPT-mediated
      DNA strand breaks.

PMID- 15505425
TI  - Acidic-rich region of amyloid precursor protein induces glial cell apoptosis.
AB  - Amyloid precursor protein (APP) has several caspase cleavage sites in its C
      terminal cytoplasmic domain and N-terminal extracellular domain. Caspase
      cleavages of APP at its cytosolic tail may result in releasing the domain and
      inducing cell death. During apoptosis, the N-terminal domain may also be
      processed at amino acids 197 and 219 by caspases leading to unmasking of an
      acidic-rich region (AR). In this study, AR-exposing APP was shown to inhibit cell
      growth after transfection into RBA-1 astrocytes and BV-2 microglial cells. The
      recombinant AR from residue 220 to 288 of APP (APP220-288) was produced and its
      biological activities were analyzed. APP220-288 induced morphological changes,
      cell death, and DNA fragmentation in BV-2 and RBA-1 cells. However, AR was
      determined to have no apparent effects in suspension cells, erythroleukemia K562
      cells, and Jurkat T cells. The cytotoxicity was depending on negative charge
      cluster and the apoptotic activity of AR was attributed to the inhibition of cell
      adhesion. In BV-2 microglial cells, AR significantly stimulated Fas expression,
      although expressions of the pro-inflammatory cytokine genes were not detected.
      APP220-288 also induced nitric oxide synthase (iNOS) expression and nitric oxide
      (NO) production. These findings indicate that the acidic-rich domain of APP may
      have apoptotic activity due to inhibition of cell adhesion and induction of iNOS
      and Fas expressions. Moreover, unmasking the apoptosis-induced AR may activate
      and exacerbate glial cells which in turn lead to further progression of the death
      program.

PMID- 15505426
TI  - Suppression of apoptosis in perfusion culture of Myeloma NS0 cells enhances cell
      growth but reduces antibody productivity.
AB  - A spin filter perfusion systems was used to achieve a high cell density culture
      for two NS0 cell lines in 2 litres bioreactors. One cell line is transfected with
      the bcl-2 gene (NS0 Bcl-2) encodes the 'anti-apoptotic' human Bcl-2 protein and
      the other cell line (NS0 Control) with a blank vector. The runs started as batch
      cultures for two days and were perfused with fresh medium at 0.5 volumes per day
      (day(-1)) for 4 days, increasing gradually to 2 day(-1) at day 7. The increase of
      the viable cell density of Bcl-2 cell line was far greater than the control cell
      line, although they were perfused with the same amount of medium. At the end of
      the period of each perfusion rate, the viable cell densities of Bcl-2 culture
      were 30%, 120%, 160% and 220% higher than its control cell line corresponding
      values. Overall, there was a roughly 9 fold increase in viable cell density from
      the inoculum for the control culture, but almost a 30 fold increase for the Bcl-2
      culture. The mode of cell death in the control culture was initially
      predominantly by necrosis (viability higher than 80%), but apoptotic cell death
      became more significant after day 8 of the culture. Cell death in the Bcl-2
      culture was almost entirely by necrosis, although it remained at a very low level
      (less than 5%) to the termination time. The cell cycle distributions for both
      cell lines were very much similar indicating they have a similar doubling time
      and G1 to S progression rate. Interestingly, the Bcl-2 cultures exhibited reduced
      antibody specific production rate with increasing viable cell number and time.
      The volumetric production rate was, however, similar in both cultures. Bcl-2 as
      an anti-death protein allowed cells to survive and thus divide to higher cell
      densities without the need for additional nutrients. Most of the cellular energy
      in a producer cell line is used for biomass production rather than for antibody
      production, as was the case with the control cell line.

PMID- 15505427
TI  - Sensitization by glycerol for CDDP-therapy against human cultured cancer cells
      and tumors bearing mutated p53 gene.
AB  - To clarify effective chemotherapeutic regimens against cancer, we examined the
      effects of glycerol on apoptosis induced by CDDP treatment using cultured human
      cancer cells (in vitro) and transplanted tumor in mice (in vivo). Human tongue
      cell carcinoma (SAS) cells transfected with mutated p53 gene (SAS/m p53) showed
      CDDP-resistance compared with the cells with neo control gene (SAS/ neo). When
      those cultured cells were pre-treated with glycerol, CDDP-induced apoptosis was
      enhanced by glycerol in SAS/m p53 cells but not in SAS/ neo cells. In tumor
      transplanted mice, the glycerol treatment to tumors enhanced growth delay induced
      by CDDP in mp53 tumors transplanted with SAS/m p53 cells, but not in wtp53 tumors
      transplanted with SAS/ neo cells. When transplanted tumors were treated with CDDP
      alone, the cells positive for active caspase-3, 85 kDa PARP and apoptosis were
      observed by immunohistochemical staining in wtp53 tumors but not in mp53 tumors.
      When the tumors were treated with CDDP combined with glycerol, positive cells
      were observed not only in wtp53 tumors but also in mp53 tumors. These results
      showed that the CDDP-induced growth inhibition of the tumors is p53 -dependent
      and that the enhanced growth delay by glycerol may be due to the increased
      apoptosis. Glycerol might be available for cancer chemotherapy in patients with
      mp53 tumors.

PMID- 15505428
TI  - [Combined-modality therapy for locoregional esophageal cancer].
AB  - Treatment for patients with esophageal cancer remains unsatisfactory. Although
      surgery alone or chemoradiotherapy have been generally accepted as reasonable
      options for patients with locoregional esophageal cancer, 5-year survival rate of
      either management is about 20%. The limited success of single modality treatment
      using radiotherapy or surgery has led to the investigation of multimodality
      therapies, combining chemotherapy, radiotherapy, and surgery. However, the
      appropriateness of such therapies remains unanswered. A number of prospective
      randomized trials of trimodality therapy versus surgery alone suggest benefits of
      combined-modality therapy. Concurrent chemoradiotherapy is an alternative
      treatment in selected resectable cases to show potential benefits in survival and
      local control. Patients with complete response following neoadjuvant therapy have
      consistent, substantial benefits in survival. Pretreatment staging is necessary
      for standardization of patients undergoing treatment protocols and for outcome
      evaluation. Biologic markers can be used to predict response to therapy and might
      allow designation of treatment based on the individual tumor. In the future,
      clinical trials testing optimal integration of preoperative regimen including new
      drugs may impact on the prognosis of esophageal cancer.

PMID- 15505429
TI  - [Expression of Cdx-2 homeobox gene in intestinal metaplasia and gastric
      adenocarcinoma].
AB  - BACKGROUND/AIMS: The Cdx-1 and Cdx-2 genes are intestinal transcription factors
      that may be involved in the regulation of proliferation and differentiation of
      intestinal epithelial cells. The Cdx-1 and Cdx-2 are expressed in the epithelium
      of the small intestine and colon but not in the normal epithelium of the
      esophagus and stomach. Conversely, aberrant Cdx-2 expression is often observed in
      the esophagus and stomach. We investigated the expression and role of Cdx-2 in
      intestinal metaplasia and gastric adenocarcinoma. METHODS: The gastric tissues
      obtained endoscopically were analyzed by the reverse transcriptase-polymerase
      chain reaction and histology. The Cdx-1 and Cdx-2 mRNA expression was confirmed
      and analyzed according to updated Sydney classification. Then,
      immunohistochemical study with monoclonal anti-Cdx-2 antibody was performed with
      gastric adenocarcinoma obtained by surgical resection. RESULTS: The prevalence of
      Cdx-1 and Cdx-2 mRNA expression was significantly higher in mucosa with
      intestinal metaplasia than mucosa without intestinal metaplasia. In
      immunohistochemical study, nuclear staining of Cdx-2 was strong in metaplastic
      mucosa, but weak in adjacent normal gastric mucosa (p<0.001). The expression of
      Cdx-2 in gastric adenocarcinoma was lower than in metaplastic mucosa (p<0.001).
      The Cdx-2 expression was also detected in 97% of intestinal type gastric
      adenocarcinoma and 61.5% of diffuse type gastric adenocarcinoma (p=0.003).
      CONCLUSIONS: Aberrant expression of Cdx-2 is observed in intestinal metaplasia
      and a subset of gastric adenocarcinoma, which is predominant in intestinal-type
      gastric adenocarcinoma. Therefore, Cdx-2 may play an important role in gastric
      carcinogenesis, especially in intestinal type adenocarcinoma.

PMID- 15505430
TI  - The impact of Helicobacter pylori infection on coronary heart disease in a Korean
      population.
AB  - BACKGROUND/AIMS: Although several studies have claimed that Helicobacter pylori
      (H. pylori) infection is related to cardiovascular disease, it is still uncertain
      whether it is related to the acute process or the chronic inflammatory
      atherosclerotic changes. The aim of our study was to confirm the impact of active
      H. pylori infection on coronary heart disease, acute inflammatory factors, and
      the coagulation factors. METHODS: A total of 94 patients completed questionnaires
      about occupation, smoking, past medical history, and socio-economic status. The
      serum of the subjects was drawn for a low density lipoprotein test, white blood
      cell count, C reactive protein, fibrinogen, homocysteine, prothrombin time,
      activated partial thrombin time, plasminogen activator inhibitor type-1, and
      tissue-type plasminogen test. All of the subjects underwent a coronary
      angiography and an upper gastrointestinal endoscopy for the diagnosis of coronary
      heart disease and H. pylori infection, respectively. RESULTS: There was no
      significant difference in acute inflammatory factors, coagulation factors,
      atheromatous burden score, and Jeopardy score between the H. pylori-infected
      group and non-infected group. Odds ratio of H. pylori infection on coronary heart
      disease was 2.59 (95% CI, 0.80-6.17), but it diminished below 1.0 (95% CI, 0.14
      1.36) after adjusting for conventional risk factors such as age, gender,
      diabetes, hypertension, smoking, body mass index and socio-economic status.
      CONCLUSIONS: H. pylori infection is not an independent risk factor for coronary
      heart disease, and it does not alter the coagulation system or evoke the systemic
      inflammatory response.

PMID- 15505431
TI  - [The diagnostic validity of Helicobacter pylori stool antigen test in the pre-
      and post-eradication].
AB  - BACKGROUND/AIMS: The efficacy of a new enzyme immunoassay designed to detect H.
      pylori antigens in stool (HpSA) was evaluated before and after the eradication
      therapy. METHODS: HpSA test was performed in 75 patients whose H. pylori status
      was defined on the basis of concordant results of the 13C-urea breath test (13C
      UBT), rapid urease test and histology. Fifty-one H. pylori-positive patients were
      treated with a week regimen of triple therapy (amoxicillin 1.0 g b.d.,
      clarithromycin 500 mg b.d., rabeprazole 10 mg b.d). Four weeks after the
      completion of therapy, previous tests including HpSA were repeated on 29 of 51
      patients. Six weeks after the completion of therapy, HpSA test was repeated on 10
      of 29 patients. RESULTS: Before the eradication, the sensitivity, specificity,
      and accuracy of HpSA test was 80.4%, 95.2% and 84.7%, respectively. When the cut
      off value of 0.12 was adopted on the basis of our receiver operation
      characteristics (ROC) curve, the sensitivity and specificity improved as 90.0%
      and 95.2%. Four weeks after the completion of therapy, the sensitivity,
      specificity and accuracy of HpSA test was 50.0%, 88.9% and 86.2%, respectively.
      In 3 patients, false positive results at 4th week were converted to true negative
      at 6 weeks. CONCLUSIONS: The HpSA test is a useful diagnostic method for H.
      pylori in pre-eradication stage. The specificity of HpSA test in the post
      eradication was similar to other studies. For the velue of HpSA test in the post
      eradication period, further studies about the cut-off value and the guideline of
      optimal time after the eradication may be needed.

PMID- 15505432
TI  - [Cyclooxygenase-2 expression according to size and location of gastric and
      colorectal tubular adenomas].
AB  - BACKGROUND/AIMS: Recent studies have shown that cyclooxygenase-2 (COX-2) may be
      involved in the process of invasion, growth and apoptosis in colorectal carcinoma
      and in the growth and tumorigenesis in familial adenomatous polyposis. This study
      was conducted to determine the significance of the expression of COX-2 in gastric
      and colorectal adenomas. METHODS: Forty-nine samples of gastric adenoma and fifty
      seven samples of colorectal adenoma were obtained by endoscopic mucosal resection
      or polypectomy from 106 patients from January 2000 to July 2003. COX-2 expression
      was determined by immunohistochemistry. Correlation between COX-2 expression and
      several clinical factors were compared in each gastric and colorectal adenomas.
      RESULTS: The expression of COX-2 in epithelial cells was significantly higher in
      the group with large adenoma (>1 cm) compared with the group with small adenoma
      (< or =1 cm) in gastric (76.5% vs. 46.7%, p=0.04) and colorectal adenomas (75%
      vs. 41.5%, p=0.023). Moreover, increased COX-2 expression was shown in distal
      compared to proximal colorectal adenoma (64.3% vs. 37.9%, p=0.047). CONCLUSIONS:
      COX-2 was expressed in a size-dependent manner in gastric and colorectal tubular
      adenomas. The expression of COX-2 was different according to the location of
      colorectal adenoma. The association of COX-2 expression with the size of adenoma
      may suggest that the role of COX-2 is not related to the early development of
      adenoma, but related to the progression of adenoma.

PMID- 15505433
TI  - [Patterns of metachronous adenoma after colorectal cancer surgery].
AB  - BACKGROUND/AIMS: After colorectal cancer surgery, colonoscopic surveillance
      should be done for prevention and early detection of secondary cancer. This study
      aimed to identify the group with high risk of developing colorectal adenoma after
      curative surgery of colorectal cancer. METHODS: We retrospectively investigated
      the medical records of the subjects of 130 patients who had been examined using
      colonoscopy before and after the curative surgery. RESULTS: The average age was
      59.4 years. Synchronous adenomas were in 42 patients (32.3%). The occurrence rate
      was significantly high in men (38.8%) than women (22.0%). After the operation,
      the mean interval of examining colonoscopy was 11.6 months (3-24 months) and
      metachronous adenomas were detected in 26 patients (20.0%). The patients who have
      both metachronous and synchronous adenomas were observed in 13/42 (30.9%) and the
      patients of metachronous adenomas without synchronous adenomas were observed in
      13/88 (14.8%). The occurrence rate of metachronous adenomas with synchronous
      adenomas was significantly high. The frequency of synchronous adenomas didn't
      increase with age. However, the frequency of metachronous adenomas increased with
      age: 0/9 (0%) under 40 years, 7/49 (14.3%) in 41-61 years and 19/72 (26.4%) over
      61 years. The occurrence rate was higher in men (26.3%) than women (10.0%).
      CONCLUSIONS: The occurrence rate of metachronous adenomas after colorectal cancer
      surgery was higher in the patients with synchronous adenomas, male gender and old
      aged patients.

PMID- 15505434
TI  - [Clinical features of eosinophilic gastroenteritis].
AB  - BACKGROUND/AIMS: Eosinophilic gastroenteritis (EG) is an uncommon disease with
      various gastrointestinal symptoms characterized by eosinophilic infiltration. Its
      incidence increases recently. We investigated the clinicopathologic features of
      the patients with EG. METHODS: Between January 1970 and July 2003, a total of 28
      cases of EG have been reported. By adding 3 cases diagnosed in the Eulji
      Hospital, we evaluated the 31 cases of EG for the symptoms, laboratory findings,
      histologic findings, method of treatment, and allergic history. RESULTS: The
      incidence increased during 1990s. The predominant site of the eosinophilic
      infiltration was mucosa in 10 cases, muscularis in 5 cases, and subserosa in 5
      cases. The remaining 11 patients had the EG in two sites. The most frequently
      affected organ was small intestine (12 patients), but there were 12 cases which
      more than two organs involved. Melena and hematochezia were dominant findings in
      the patients whose infiltration occurred in mucosa. On the other hand, ascites
      was a dominant finding in the cases that infiltration occurred in subserosa or
      involving over 2 layers. There was no difference in eosinophilia, clinical
      symptoms, and duration between two groups according to the symptom duration for
      less or more than 30 days. Additionally, seven patients had allergic histories.
      Peripheral eosinophilia was found in 24 cases. There was no recurrence of EG
      after the treatment. CONCLUSIONS: Our retrospective studies about EG reported in
      Korea could not clarify whether EG is related to allergy. Recently, the
      occurrence of EG is increasing and it is frequently involved in young men. The
      most apparent finding include peripheral eosinophilia. There is no significant
      clinical feature which is consistent with Klein's classification, though blood
      loss was more common in mucosal type and ascites was more common in serosal type
      and in case above two layers.

PMID- 15505435
TI  - Cytomegalovirus colitis manifested with a ring like ileocecal valve ulcer in a
      Korean AIDS patient.
AB  - A 32-year-old man, who had no previous medical history, was hospitalized with 3
      week duration of abdominal pain, fever, and watery diarrhea. Initial colonoscopy
      showed subepithelial hemorrhagic spots throughout the entire colon together with
      well-circumscribed ulcer around the ileocecal valve. Serologic test disclosed HIV
      positive and repeated biopsies at ulcer base finally revealed that the patient
      had cytomegalovirus ulcer in ileocecal area.

PMID- 15505436
TI  - [Diagnostic validity of the Helicobacter pylori stool antigen test before and
      after eradication treatment].

PMID- 15505438
TI  - Dexmedetomidine and opioid interactions: defining the role of dexmedetomidine for
      intensive care unit sedation.

PMID- 15505439
TI  - What makes a "good" anesthesiologist?

PMID- 15505440
TI  - Severing the link between acute and chronic pain: the anesthesiologist's role in
      preventive medicine.

PMID- 15505441
TI  - Dexmedetomidine pharmacodynamics: part I: crossover comparison of the respiratory
      effects of dexmedetomidine and remifentanil in healthy volunteers.
AB  - BACKGROUND: Dexmedetomidine, a highly selective alpha2-adrenoceptor agonist used
      for short-term sedation of mechanically ventilated patients, has minimal effect
      on ventilation. METHODS: This study compared the respiratory effect of
      dexmedetomidine to that of remifentanil. The authors measured and compared
      respiratory responses of six healthy male volunteers during (1) a stepwise target
      controlled infusion of remifentanil, (2) a stepwise target-controlled infusion of
      dexmedetomidine, and (3) a pseudonatural sleep session. RESULTS: Compared with
      baseline, remifentanil infusions resulted in respiratory depression as evidenced
      by a decrease in respiratory rate and minute ventilation, respiratory acidosis,
      and apnea episodes resulting in desaturations. Remifentanil disturbed the natural
      pattern of breathing and flattened the distribution of ventilatory timing
      (inspiratory time/ventilatory cycle time). The respiratory effects of
      dexmedetomidine markedly contrasted with those of remifentanil. When compared
      with baseline, during dexmedetomidine infusions, the respiratory rate
      significantly increased, and the overall apnea/hypopnea index significantly
      decreased. The distribution of inspiratory time/ventilatory cycle time showed an
      increased peak. In addition, dexmedetomidine seemed to mimic some aspect of
      natural sleep. While the subjects were breathing a 5% CO2 mixture, hypercapnic
      arousal phenomena (documented by the Bispectral Index, the electroencephalogram,
      and sudden increase in the minute ventilation) were observed during
      dexmedetomidine infusions. Similar phenomena during natural sleep have been
      reported in the literature. CONCLUSIONS: In comparison with remifentanil,
      dexmedetomidine infusions (1) did not result in clinically significant
      respiratory depression, (2) decreased rather than increased the apnea/hypopnea
      index, and (3) exhibited some similarity with natural sleep.

PMID- 15505442
TI  - Dexmedetomidine pharmacodynamics: Part II: Crossover comparison of the analgesic
      effect of dexmedetomidine and remifentanil in healthy volunteers.
AB  - BACKGROUND: Dexmedetomidine is a highly selective alpha2-adrenoceptor agonist
      used for short-term sedation of mechanically ventilated patients. The analgesic
      profile of dexmedetomidine has not been fully characterized in humans. METHODS:
      This study was designed to compare the analgesic responses of six healthy male
      volunteers during stepwise target-controlled infusions of remifentanil and
      dexmedetomidine. A computer-controlled thermode was used to deliver painful heat
      stimuli to the volar side of the forearms of the subjects. Six sequential 5-s
      stimuli (ranging from 41 degrees to 50 degrees C) were delivered in random order.
      The recorded visual analog scale was used to fit an Emax model. RESULTS: Compared
      to baseline, remifentanil infusions resulted in a right shift of the sigmoid
      curve (increased T50, the temperature producing a visual analog scale score of
      50% of the maximal effect, from 46.1 degrees C at baseline to 48.4 degrees and
      49.1 degrees C during remifentanil infusions) without a change of the steepness
      of the curve (identical Hill coefficients gamma during baseline and
      remifentanil). Compared to baseline, dexmedetomidine infusions resulted in both a
      right shift of the sigmoid curve (increased T50 to 47.2 degrees C) and a decrease
      in the steepness of the curve (decreased gamma from 3.24 during baseline and
      remifentanil infusions to 2.45 during dexmedetomidine infusions). There was no
      difference in the pain responses between baseline and after recovery from
      remifentanil infusions (identical T50 and gamma). CONCLUSION: As expected,
      dexmedetomidine is not as effective an analgesic as the opioid remifentanil. The
      difference in the quality of the analgesia with remifentanil may be a reflection
      of a different mechanism of action or a consequence of the sedative effect of
      dexmedetomidine.

PMID- 15505443
TI  - Acute care skills in anesthesia practice: a simulation-based resident performance
      assessment.
AB  - BACKGROUND: A recurring initiative in graduate education is to find more
      effective methods to assess specialists' skills. Life-sized simulators could be
      used to assess the more complex skills expected in specialty practice if a
      curriculum of relevant exercises were developed that could be simply and reliably
      scored. The purpose of this study was to develop simulation exercises and
      associated scoring methods and determine whether these scenarios could be used to
      evaluate acute anesthesia care skills. METHODS: Twenty-eight residents (12 junior
      and 16 senior) managed three intraoperative and three postoperative simulation
      exercises. Trainees were required to make a diagnosis and intervention in a
      simulation encounter designed to recreate an acute perioperative complication.
      The videotaped performances were scored by six raters. Three raters used a
      checklist scoring system. Three faculty raters measured when trainees performed
      three key diagnostic or therapeutic actions during each 5-min scenario. These
      faculty also provided a global score using a 10-cm line with scores from 0
      (unsatisfactory) to 10 (outstanding). The scenarios included (1) intraoperative
      myocardial ischemia, (2) postoperative anaphylaxis, (3) intraoperative
      pneumothorax, (4) postoperative cerebral hemorrhage with intracranial
      hypertension, (5) intraoperative ventricular tachycardia, and (6) postoperative
      respiratory failure. RESULTS: The high correlation among all of the scoring
      systems and small variance among raters' scores indicated that all of the scoring
      systems measured similar performance domains. Scenarios varied in their overall
      difficulty. Even though trainees who performed well on one exercise were likely
      to perform well in subsequent scenarios, the authors found that there were
      considerable differences in case difficulty. CONCLUSION: This study suggests that
      simulation can be used to measure more complex skills expected in specialty
      training. Similar to other studies that assess a broad content domain, multiple
      encounters are needed to estimate skill effectively and accurately.

PMID- 15505444
TI  - Impact of bispectral index monitoring on stress response and propofol consumption
      in patients undergoing coronary artery bypass surgery.
AB  - BACKGROUND: Bispectral Index (BIS)-titrated administration allows a reduction of
      propofol infusion rates in patients undergoing surgery. Resulting differences in
      anesthetic depth might affect the stress response to surgery involving neural
      circuitry not reflected in the electroencephalogram. METHODS: Forty patients
      scheduled to undergo elective coronary artery bypass grafting receiving a
      background infusion of remifentanil (0.3 microg . kg . min) were anesthetized
      with intravenous propofol delivered by target-controlled infusion according to
      the Marsh pharmacokinetic model under BIS monitoring. In a randomized,
      prospective design, 20 patients received propofol at a target concentration of 3
      microg/ml, whereas in 20 patients propofol was titrated to maintain a BIS value
      of 40-50. Plasma concentrations of propofol (by means of gas chromatography-mass
      spectrometry), epinephrine, norepinephrine (by means of high-pressure liquid
      chromatography), cortisol (by means of radioimmunoassay), and interleukins 6 and
      10 (by means of enzyme-linked immunosorbent assay) were measured repeatedly
      throughout surgery. RESULTS: BIS monitoring allowed a 30% reduction of propofol
      infusion rates and a similar decrease in plasma propofol concentrations in the
      BIS group without affecting the stress response to surgery for the group mean.
      None of the patients reported awareness during a standardized interview.
      Interestingly, propofol-remifentanil anesthesia blunted the release of
      epinephrine and cortisol to bypass surgery completely even when the propofol
      infusion rate was reduced according to BIS values. CONCLUSIONS: Total intravenous
      anesthesia using propofol-remifentanil effectively attenuates the neurohumoral
      stress response to coronary bypass surgery involving cardiopulmonary bypass.
      Titration of propofol using BIS allows for significant reduction of propofol
      consumption, with only minor effects on stress response under these conditions.

PMID- 15505445
TI  - Narcotrend does not adequately detect the transition between awareness and
      unconsciousness in surgical patients.
AB  - BACKGROUND: The Narcotrend index (MonitorTechnik, Bad Bramstedt, Germany) is a
      dimensionless number between 0 and 100 that is calculated from the
      electroencephalogram and inversely correlates with depth of hypnosis. The current
      study evaluates the capability of the Narcotrend to separate awareness from
      unconsciousness at the transition between these levels. METHODS:
      Electroencephalographic recordings of 40 unpremedicated patients undergoing
      elective surgery were analyzed. Patients were randomly assigned to receive (1)
      sevoflurane-remifentanil (</= 0.1 microg . kg . min), (2) sevoflurane
      remifentanil (>/= 0.2 microg . kg . min), (3) propofol-remifentanil (</= 0.1
      microg . kg . min), or (4) propofol-remifentanil (>/= 0.2 microg . kg . min).
      Remifentanil and sevoflurane or propofol were given until loss of consciousness.
      After tracheal intubation, propofol or sevoflurane was stopped until return of
      consciousness and then restarted to induce loss of consciousness. After surgery,
      drugs were discontinued. Narcotrend values at loss and return of consciousness
      were compared with each other, and anesthetic groups were compared. Prediction
      probability was calculated from values at the last command before and at loss and
      return of consciousness. RESULTS: At 105 of 316 analyzed time points, the
      Narcotrend did not calculate an index, and the closest calculated value was
      analyzed. No significant differences between loss and return of consciousness
      were found. In group 1, Narcotrend values were significantly higher than in group
      3. Prediction probability was 0.501. CONCLUSIONS: In these challenging data, the
      Narcotrend did not differentiate between awareness and unconsciousness. In
      addition, Narcotrend values were not independent from the anesthetic regimen.

PMID- 15505446
TI  - Induction speed is not a determinant of propofol pharmacodynamics.
AB  - BACKGROUND: Evidence suggests that the rate at which intravenous anesthetics are
      infused may influence their plasma-effect site equilibration. The authors used
      five different rates of propofol administration to test the hypothesis that
      different sedation endpoints occur at the same effect site propofol
      concentration, independent of the infusion rate. The authors concurrently
      evaluated the automated responsiveness monitor (ARM) against other sedation
      measures and the propofol effect site concentration. METHODS: With Human Studies
      Committee approval, 18 healthy volunteers received five consecutive target
      controlled propofol infusions. During each infusion, the effect site
      concentration was increased by a rate of 0.1, 0.3, 0.5, 0.7, or 0.9 microg . ml .
      min. The Bispectral Index and ARM were recorded at frequent intervals. The times
      of syringe drop and loss and recovery of responsiveness were noted.
      Pharmacokinetic and pharmacodynamic modeling was performed using NONMEM. RESULTS:
      When the correct rate of plasma-effect site equilibration was determined for each
      individual (plasma-effect site equilibration = 0.17 min, time to peak effect =
      2.7 min), the effect site concentrations associated with each clinical measure
      were not affected by the rate of increase of effect site propofol concentration.
      ARM correlated with all clinical measures of drug effect. Subjects invariably
      stopped responding to ARM at lower effect site propofol concentrations than those
      associated with loss of responsiveness. CONCLUSIONS: : Population-based
      pharmacokinetics, combined with real-time electroencephalographic measures of
      drug effect, may provide a means to individualize pharmacodynamic modeling during
      target-controlled drug delivery. ARM seems useful as an automated measure of
      sedation and may provide the basis for automated monitoring and titration of
      sedation for a propofol delivery system.

PMID- 15505447
TI  - Comparison of cisatracurium and vecuronium by infusion in neonates and small
      infants after congenital heart surgery.
AB  - BACKGROUND: Neonates and infants often require extended periods of mechanical
      ventilation facilitated by sedation and neuromuscular blockade. METHODS: Twenty
      three patients aged younger than 2 yr were randomly assigned to receive either
      cisatracurium or vecuronium infusions postoperatively in a double-blinded fashion
      after undergoing congenital heart surgery. The infusion was titrated to maintain
      one twitch of a train-of-four. The times to full spontaneous recovery of train-of
      four without fade, extubation, intensive care unit discharge, and hospital
      discharge were documented after drug discontinuation. Sparse sampling after
      termination of the infusion and a one-compartment model were used for
      pharmacokinetic analysis. The Mann-Whitney U test and Student t test were used to
      compare data between groups. RESULTS: There were no significant differences
      between groups with respect to demographic data or duration of postoperative
      neuromuscular blockade infusion. The median recovery time for train-of-four for
      cisatracurium (30 min) was less than that for vecuronium (180 min) (P < 0.05).
      Three patients in the vecuronium group had prolonged train-of-four recovery: Two
      had long elimination half-lives for vecuronium, and one had a high concentration
      of 3-OH vecuronium. There were no differences in extubation times, intensive care
      unit stays, or hospital stays between groups. CONCLUSIONS: Our results parallel
      data from adults demonstrating a markedly shorter recovery of neuromuscular
      transmission after cisatracurium compared with vecuronium. Decreased clearance of
      vecuronium and the accumulation of 3-OH vecuronium may contribute to prolonged
      spontaneous recovery times. Cisatracurium is associated with faster spontaneous
      recovery of neuromuscular function compared with vecuronium but not with any
      differences in intermediate outcome measures in neonates and infants.

PMID- 15505448
TI  - Isoflurane alters the amount of dopamine transporter expressed on the plasma
      membrane in humans.
AB  - BACKGROUND: Isoflurane increases extracellular dopamine concentration and causes
      trafficking of the dopamine transporter (DAT) in transfected cells. Also, the
      binding potentials of highly specific positron-emitting DAT ligands are altered
      by isoflurane in rhesus monkeys. The purpose of this study was to determine the
      dose-response curve for isoflurane altering the binding potential of one of these
      ligands ([F-18]FECNT) in humans. METHODS: Twenty human volunteers underwent
      positron emission tomography using [F-18]FECNT. All subjects were scanned while
      awake and then again after assignment to one of four groups (n = 5 each): awake
      control, propofol-control, or light or deep isoflurane anesthesia as defined by
      Bispectral Index monitoring. Bispectral Index values in the light anesthesia
      group were 40 +/- 7 (end-tidal isoflurane, 1.02 +/- 0.08) versus 27 +/- 10 (end
      tidal isoflurane, 1.6 +/- 0.3) in the deep anesthesia group. The within-subject
      percent change in putamen binding potential between the awake and second scans
      was determined for each subject, averaged within groups, and compared across
      groups. RESULTS: The [F-18]FECNT binding potential exhibited a biphasic shape as
      a function of anesthetic dose. The binding potential for the second scan in the
      awake-control and propofol-control groups was significantly less than the initial
      scan; for the light anesthesia group, the binding potential was significantly
      increased during anesthesia, and no change was detected between the two scans in
      the deeper anesthesia group. CONCLUSION: Isoflurane causes a dose-dependent
      change in the [F-18]FECNT binding potential for DAT consistent with isoflurane
      causing trafficking of the DAT between the plasma membrane and the cell interior.
      Concentrations of isoflurane below minimum alveolar concentration causes DAT to
      be trafficked to the plasma membrane from the cell interior, but no net
      trafficking occurs at higher concentrations. The data are most easily explained
      if isoflurane alters the amount of functionally expressed DAT through an indirect
      pathway. This phenomena should be more fully explored to help make the next
      generation of anesthetics more mechanistically specific and to reduce undesired
      side effects.

PMID- 15505449
TI  - Effects of different catecholamines on the dynamics of volume expansion of
      crystalloid infusion.
AB  - BACKGROUND: The authors studied the influence of alpha, beta, and dopaminergic
      catecholamines on blood volume expansion in conscious normovolemic sheep before,
      during, and after a bolus infusion of a crystalloid. METHODS: A 0.9% NaCl bolus
      (24 ml/kg in 20 min) was infused in four paired experiments each: no drug,
      dopamine infusion (50 microg . kg . min), isoproterenol infusion (0.1 microg . kg
      . min), and phenylephrine infusion (3 microg . kg . min). Blood volume expansion
      was calculated by the dilution of blood hemoglobin concentration. RESULTS:
      Dopamine had little effect on peak blood volume expansion (12.7 +/- 0.9 ml/kg)
      compared with 0.9% NaCl (13.0 +/- 2.7 ml/kg); in contrast, isoproterenol
      augmented blood volume expansion (18.5 +/- 1.8 ml/kg), and phenylephrine reduced
      blood volume expansion (8.9 +/- 1.4 ml/kg). Two hours after the 0.9% NaCl bolus,
      sustained blood volume expansion was greatest in the isoproterenol protocol (12.2
      ml/kg), whereas the dopamine protocol (6.8 ml/kg) remained similar to the control
      protocol (4.1 ml/kg), and the phenylephrine protocol had a net volume loss (-1.9
      ml/kg). Some blood volume expansion differences were attributed to changes in
      renal function as phenylephrine infusion increased urinary output, whereas
      isoproterenol was associated with antidiuresis. However, dopamine caused diuresis
      and sustained augmentation of blood volume. CONCLUSION: Catecholamines can alter
      the intravascular volume expansion of fluid therapy. beta-Receptor
      (isoproterenol) stimulation augmented blood volume expansion, whereas alpha
      (phenylephrine) stimulation reduced blood volume expansion. Combined
      dopaminergic, beta, and possibly alpha stimulation with dopamine augmented blood
      volume expansion and cardiac output while inducing diuresis.

PMID- 15505450
TI  - Interaction of halogenated anesthetics with alpha- and beta-adrenoceptor
      stimulations in diabetic rat myocardium.
AB  - BACKGROUND: Halogenated anesthetics potentiate the positive inotropic effects of
      alpha- and beta-adrenoceptor stimulations. Although diabetes mellitus induces
      significant myocardial abnormalities, the interaction of halogenated anesthetics
      and adrenoceptor stimulation in diabetic myocardium remains unknown. METHODS:
      Left ventricular papillary muscles were provided from healthy and streptozotocin
      induced diabetic rats. Effects of 1 minimum alveolar concentration halothane,
      isoflurane, and sevoflurane on the inotropic and lusitropic responses of alpha
      (phenylephrine)- and beta (isoproterenol)-adrenoceptor stimulations were studied
      at 29 degrees C with 12 pulses/min. Data shown are mean percentage of baseline
      active force +/- SD. RESULTS: Phenylephrine induced comparable positive inotropic
      effects in healthy and diabetic rats (143 +/- 8 vs. 136 +/- 18%; not
      significant), but the potentiation by halogenated anesthetics was abolished in
      the diabetic rats (121 +/- 20, 130 +/- 20, and 123 +/- 20% for halothane,
      isoflurane, and sevoflurane, respectively; not significant). In diabetic rats,
      the positive inotropic effect of isoproterenol was markedly diminished (109 +/- 9
      vs. 190 +/- 18%; P < 0.05), but its potentiation was preserved with isoflurane
      (148 +/- 21%; P < 0.05) and sevoflurane (161 +/- 40%; P < 0.05) but not with
      halothane (126 +/- 16%; not significant). Halothane induced a deleterious effect
      on the sarcoplasmic reticulum, as shown by its impairment in the lusitropic
      effect of isoproterenol, compared with isoflurane and sevoflurane. CONCLUSION:
      Potentiation of the positive inotropic effect of alpha-adrenoceptor stimulation
      by halogenated anesthetics is abolished in diabetic rats. In contrast,
      potentiation of beta-adrenoceptor stimulation is preserved with isoflurane and
      sevoflurane but not with halothane, probably because of its deleterious effects
      on sarcoplasmic reticulum.

PMID- 15505451
TI  - Activation of A3 adenosine receptors attenuates lung injury after in vivo
      reperfusion.
AB  - BACKGROUND: A3 adenosine receptor (AR) activation worsens or protects against
      renal and cardiac ischemia-reperfusion (IR) injury, respectively. The aims of the
      current study were to examine in an in vivo model the effect of A3AR activation
      on IR lung injury and investigate the mechanism by which it exerts its effect.
      METHODS: The arterial branch of the left lower lung lobe in intact-chest,
      spontaneously breathing cats was occluded for 2 h and reperfused for 3 h (IR
      group). Animals were treated with the selective A3 receptor agonist IB-MECA (300
      microg/kg intravenously) given 15 min before ischemia or with IB-MECA as
      described, with pretreatment 15 min earlier with the selective A3AR antagonist
      MRS-1191, the nonsulfonylurea adenosine triphosphate-sensitive potassium channel
      blocking agent U-37883A, or the nitric oxide synthase inhibitor N-nitro-l
      arginine benzyl ester. RESULTS: IB-MECA markedly (P < 0.01) reduced the
      percentage of injured alveoli (IR, 48 +/- 4%; IB-MECA, 18 +/- 2%), wet:dry weight
      ratio (IR, 8.2 +/- 0.4; IB-MECA, 4 +/- 2), and myeloperoxidase activity (IR, 0.52
      +/- 0.06 U/g; IB-MECA, 0.17 +/- 0.04 U/g). This protective effect was completely
      blocked by pretreatment with the selective A3AR antagonist MRS-1191 and the
      adenosine triphosphate-sensitive potassium channel blocking agent U-37883A but
      not the nitric oxide synthase inhibitor N-nitro-l-arginine benzyl ester.
      CONCLUSIONS: In the feline lung, the A3AR agonist IB-MECA confers a powerful
      protection against IR lung injury. This effect is mediated by a nitric oxide
      synthase-independent pathway and involves opening of adenosine triphosphate
      sensitive potassium channels. Therefore, selective activation of A3AR may be an
      effective means of protecting the reperfused lung.

PMID- 15505452
TI  - Intravenous emulsified halogenated anesthetics produce acute and delayed
      preconditioning against myocardial infarction in rabbits.
AB  - BACKGROUND: Preconditioning against myocardial infarction by volatile anesthetics
      is well known. The authors tested the hypothesis that new emulsified formulations
      of halogenated anesthetics administered intravenously reduce myocardial infarct
      size when administered either 1 or 24 h before prolonged ischemia and
      reperfusion. METHODS: Pentobarbital-anesthetized rabbits (n = 39) were
      instrumented for measurement of hemodynamics and randomly assigned to receive
      intravenous saline (control), lipid vehicle, or infusions (3.5 ml . kg . h for 30
      min) of emulsified isoflurane (6.9%), enflurane (7.1%), or sevoflurane (7.5%).
      Infusions were discontinued 30 min before a 30-min coronary occlusion and 3 h of
      reperfusion. In three additional groups, conscious rabbits (n = 21) received
      saline, lipid vehicle, or emulsified sevoflurane (7.5%) infusions (3.5 ml . kg .
      h for 30 min) 24 h before ischemia and reperfusion. Infarct size was determined
      using triphenyltetrazolium staining. RESULTS: Lipid vehicle produced transient
      increases in heart rate, whereas emulsified volatile anesthetics had no effect on
      hemodynamics before coronary occlusion. Lipid vehicle did not affect infarct size
      (38 +/- 2% of the area at risk; mean +/- SEM) as compared with saline control (41
      +/- 4%). In contrast, emulsified isoflurane, enflurane, and sevoflurane reduced
      infarct size (20 +/- 3%, 20 +/- 3%, and 21 +/- 2% of the area at risk,
      respectively; P < 0.05). Administration of lipid vehicle or emulsified
      sevoflurane did not produce sedation or respiratory depression in conscious
      rabbits. Emulsified sevoflurane (18 +/- 2%) but not lipid vehicle (44 +/- 2%)
      reduced infarct size as compared with control in delayed preconditioning
      experiments. CONCLUSIONS: Intravenous emulsified halogenated anesthetics produce
      acute and delayed preconditioning against myocardial infarction.

PMID- 15505453
TI  - Propofol and sevoflurane depress spinal neurons in vitro via different molecular
      targets.
AB  - BACKGROUND: The capacity of general anesthetics to produce immobility is
      primarily spinally mediated. Recently, compelling evidence has been provided that
      the spinal actions of propofol involve gamma-aminobutyric acid type A (GABAA)
      receptors, whereas the contribution of glycine receptors remains uncertain. The
      relevant molecular targets of the commonly used volatile anesthetic sevoflurane
      in the spinal cord are largely unknown, but indirect evidence suggests a
      mechanism of action distinct from propofol. METHODS: The effects of sevoflurane
      and propofol on spontaneous action potential firing were investigated by
      extracellular voltage recordings from ventral horn interneurons in cultured
      spinal cord tissue slices obtained from embryonic rats (embryonic days 14-15).
      RESULTS: Propofol and sevoflurane reduced spontaneous action potential firing of
      neurons. Concentrations causing half-maximal effects (0.11 microm propofol, 0.11
      mm sevoflurane) were lower than the median effective concentration immobility (1
      1.5 microm propofol, 0.35 mm sevoflurane). At higher concentrations, complete
      inhibition of action potential activity was observed with sevoflurane but not
      with propofol. Effects of sevoflurane were mediated predominantly by glycine
      receptors (45%) and GABAA receptors (38%), whereas propofol acted almost
      exclusively via GABAA receptors (96%). CONCLUSIONS: The authors' results suggest
      that glycine and GABAA receptors are the most important molecular targets
      mediating depressant effects of sevoflurane in the spinal cord. They provide
      evidence that sevoflurane causes immobility by a mechanism distinct from the
      actions of the intravenous anesthetic propofol. The finding that propofol acts
      exclusively via GABAA receptors can explain its limited capacity to depress
      spinal neurons in the authors' study.

PMID- 15505454
TI  - Selective postsynaptic inhibition of tonic-firing neurons in substantia
      gelatinosa by mu-opioid agonist.
AB  - BACKGROUND: Spinal substantia gelatinosa (SG) is a site of action of administered
      and endogenous opioid agonists and is an important element in the system of
      antinociception. However, little is known about the types of neurons serving as
      specific postsynaptic targets for opioid action within the SG. To study the
      spinal mechanisms of opioidergic analgesia, the authors compared the action of mu
      opioid agonist [D-Ala, N-Me-Phe, Gly-ol]-enkephalin (DAMGO) on SG neurons with
      different intrinsic firing properties. METHODS: Whole cell patch clamp recordings
      from spinal cord slices of Wistar rats were used to study the sensitivity of SG
      neurons to DAMGO. RESULTS: Three groups of neurons with distinct distributions in
      SG were classified: tonic-, adapting-, and delayed-firing neurons. DAMGO at 1
      microm concentration selectively hyperpolarized all tonic-firing neurons tested,
      whereas none of the adapting- or delayed-firing neurons were affected. The effect
      of DAMGO on tonic-firing neurons was due to activation of G protein-coupled
      inward-rectifier K conductance, which could be blocked by 500 microm Ba and 500
      microm Cs but increased by 50 microm baclofen. As a functional consequence of
      DAMGO action, a majority of tonic-firing neurons changed their pattern of
      intrinsic firing from tonic to adapting. CONCLUSIONS: It is suggested that tonic
      firing neurons, presumably functioning as excitatory interneurons, are primary
      postsynaptic targets for administered and endogenous opioid agonists in spinal
      SG. Functional transition of cells in this group from tonic to adapting firing
      mode may represent an important mechanism facilitating opioidergic analgesia.

PMID- 15505455
TI  - Mitochondrial injury and caspase activation by the local anesthetic lidocaine.
AB  - BACKGROUND: Lidocaine, a local anesthetic, can be neurotoxic. However, the
      cellular mechanisms of its neurotoxicity at concentrations encountered during
      spinal anesthesia remain unclear. METHODS: The authors examined the mechanisms of
      lidocaine neurotoxicity in the ND7 cell line derived from rat dorsal root
      ganglion. Individual neurons were assayed by flow cytometry or microscopy using
      fluorescent probes of plasma membrane integrity, mitochondrial membrane
      potential, caspase activity, phospholipid membrane asymmetry, and mitochondrial
      cytochrome c release. RESULTS: In the ND7 cell line, lidocaine at 185 mm x 10 min
      to 2.3 mm x 24 h caused necrosis or late apoptosis. Equimolar Tris buffer and
      equipotent tetrodotoxin controls were not toxic, indicating that neither osmotic
      nor Na-blocking effects explain lidocaine neurotoxicity. The earliest
      manifestation of lidocaine neurotoxicity was complete loss of mitochondrial
      membrane potential within 5 min after exposure to lidocaine at a concentration of
      19 mm or greater. Consistent with these data, 37 mm lidocaine (1%) induced
      release of mitochondrial cytochrome c into the cytoplasm, as well as plasma
      membrane blebbing, loss of phosphatidylserine membrane asymmetry, and caspase
      activation, with release of mitochondrial cytochrome c to the cytoplasm within 2
      h. Treatment with z-VAD-fmk, a specific inhibitor of caspases, prevented caspase
      activation and delayed but did not prevent neuronal death, but did not inhibit
      the other indicators of apoptosis. CONCLUSIONS: Collectively, these data indicate
      that lidocaine neurotoxicity involves mitochondrial dysfunction with activation
      of apoptotic pathways.

PMID- 15505456
TI  - Ultrasound-guided lumbar facet nerve block: accuracy of a new technique confirmed
      by computed tomography.
AB  - BACKGROUND: Lumbar facet nerve (medial branch) blocks are often used to diagnose
      facet joint-mediated pain. The authors recently described a new ultrasound-guided
      methodology. The current study determines its accuracy using computed tomography
      scan controls. METHODS: Fifty bilateral ultrasound-guided approaches to the
      lumbar facet nerves were performed in five embalmed cadavers. The target point
      was the groove at the cephalad margin of the transverse (or costal) process L1-L5
      (medial branch T12-L4) adjacent to the superior articular process. Axial
      transverse computed tomography scans, with and without 1 ml contrast dye,
      followed to evaluate needle positions and spread of contrast medium. RESULTS:
      Forty-five of 50 needle tips were located at the exact target point. The
      remaining 5 were within 5 mm of the target. In 47 of 50 cases, the applied
      contrast dye reached the groove where the nerve is located, corresponding to a
      simulated block success rate of 94% (95% confidence interval, 84-98%). Seven of
      50 cases showed paraforaminal spread, 5 of 50 showed epidural spread, and 2 of 50
      showed intravascular spread. Despite the aberrant distribution, all of these
      approaches were successful, as indicated by contrast dye at the target point.
      Abnormal contrast spread was equally distributed among all lumbar levels.
      Contrast traces along the needle channels were frequently observed. CONCLUSIONS:
      : The computed tomography scans confirm that our ultrasound technique for lumbar
      facet nerve block is highly accurate for the target at all five lumbar transverse
      processes (medial branches T12-L4). Aberrant contrast medium spread is comparable
      to that of the classic fluoroscopy-guided method.

PMID- 15505457
TI  - Simultaneous measurement and integrated analysis of analgesia and respiration
      after an intravenous morphine infusion.
AB  - BACKGROUND: To study the influence of morphine on chemical control of breathing
      relative to the analgesic properties of morphine, the authors quantified morphine
      induced analgesia and respiratory depression in a single group of healthy
      volunteers. Both respiratory and pain measurements were performed over single 24
      h time spans. METHODS: Eight subjects (four men, four women) received a 90-s
      intravenous morphine infusion; eight others (four men, four women) received a 90
      s placebo infusion. At regular time intervals, respiratory variables (breathing
      at a fixed end-tidal partial pressure of carbon dioxide of 50 mmHg and the
      isocapnic acute hypoxic response), pain tolerance (derived from a transcutaneous
      electrical acute pain model), and arterial blood samples were obtained. Data
      acquisition continued for 24 h. Population pharmacokinetic (sigmoid Emax)
      pharmacodynamic models were applied to the respiratory and pain data. The models
      are characterized by potency parameters, shape parameters (gamma), and blood
      effect site equilibration half-lives. All collected data were analyzed
      simultaneously using the statistical program NONMEM. RESULTS: Placebo had no
      systematic effect on analgesic or respiratory variables. Morphine potency
      parameter and blood-effect site equilibration half-life did not differ
      significantly among the three measured effect parameters (P > 0.01). The
      integrated NONMEM analysis yielded a potency parameter of 32 +/- 1.4 nm (typical
      value +/- SE) and a blood-effect site equilibration half-life of 4.4 +/- 0.3 h.
      Parameter gamma was 1 for hypercapnic and hypoxic breathing but 2.4 +/- 0.7 for
      analgesia (P < 0.01). CONCLUSIONS: Our data indicate that systems involved in
      morphine-induced analgesia and respiratory depression share important
      pharmacodynamic characteristics. This suggests similarities in central mu-opioid
      analgesic and respiratory pathways (e.g., similarities in mu-opioid receptors and
      G proteins). The clinical implication of this study is that after morphine
      administration, despite lack of good pain relief, moderate to severe respiratory
      depression remains possible.

PMID- 15505458
TI  - Introduction of anesthesia resident trainees to the operating room does not lead
      to changes in anesthesia-controlled times for efficiency measures.
AB  - BACKGROUND: Operating room efficiency is an important concern in most hospitals
      today. Little work has been reported to evaluate the contribution of anesthesia
      residents to changes in anesthesia-controlled time-related efficiencies in the
      operating room. The goal of this study was to measure the impact of the
      initiation of new residents to the operating room on anesthesia-related time
      measures of operating room efficiency. METHODS: Using the computerized operating
      room information systems, specific data regarding anesthesia-controlled times
      were extracted over three distinct 2-week periods over the course of 1 academic
      year. These included the first 2 weeks of July, when most of the operating rooms
      were staffed by attending physicians working alone; 2 weeks in September when new
      anesthesia residents were working in a 2:1 ratio with staff; and 2 weeks in May.
      The induction times, emergence times, and room turnover times were compared over
      these three periods for first-year anesthesia residents. Standard descriptive
      statistics were computed. Analysis of variance testing was then conducted
      comparing each of these time periods. Significance was set at P < 0.05. RESULTS:
      A total of 3,004 surgical procedures were performed during the 2-week study
      periods in July, September, and May, respectively. For the July, September, and
      May groups, the mean anesthesia induction times were 17.3, 19.0, and 20.8 min (P
      = 0.047); the emergence times were 8.7, 9.7, and 10.0 min, (P = 0.024); and the
      corresponding mean room turnover times were 47.6, 48.5, and 48.6 min (P = 0.907),
      respectively. CONCLUSION: Although statistically significant time differences
      were found, these data strongly suggest that the initiation of anesthesia
      trainees to the operating room has no clinically or economically meaningful
      adverse effect on the anesthesia-controlled time component of operating room
      efficiency.

PMID- 15505459
TI  - Preventing the development of complex regional pain syndrome after surgery.

PMID- 15505460
TI  - Weak intermolecular associations and anesthesia.

PMID- 15505461
TI  - Auto-positive end-expiratory pressure masquerading as loss of lung separation
      during thoracoscopy.

PMID- 15505462
TI  - Emergency treatment of tracheobronchial stent migration.

PMID- 15505463
TI  - Perioperative compartment syndrome of the hand.

PMID- 15505464
TI  - Severe subluxation in the sniffing position in a rheumatoid patient with anterior
      atlantoaxial subluxation.

PMID- 15505465
TI  - Cervical epidural steroid injection: impact of cervical epidural anatomy.

PMID- 15505466
TI  - No granuloma and no intracranial hypotension.

PMID- 15505468
TI  - Unassisted gum elastic bougie-guided insertion of the ProSeal laryngeal mask
      airway.

PMID- 15505469
TI  - The Eschmann tracheal tube introducer is not gum, elastic, or a bougie.

PMID- 15505470
TI  - Bleeding, dysphagia, dysphonia, dysarthria, severe sore throat, and possible
      recurrent laryngeal, hypoglossal, and lingual nerve injury associated with
      routine laryngeal mask airway management: where is the vigilance?

PMID- 15505472
TI  - Is there any reason to withhold alpha2 agonists from patients with coronary
      disease during surgery?

PMID- 15505475
TI  - In defense of in vitro findings.

PMID- 15505477
TI  - Chloroprocaine or sulfite toxicity?

PMID- 15505479
TI  - Questioning the mechanism of nerve injury.

PMID- 15505480
TI  - Movement of the Cauda Equina during the lateral decubitus position with fully
      flexed leg.

PMID- 15505481
TI  - A modified rapid sequence induction using the ProSeal laryngeal mask airway and
      an Eschmann tracheal tube introducer or gum elastic bougie.

PMID- 15505482
TI  - GlideScope-assisted fiberoptic intubation: a new airway teaching method.

PMID- 15505483
TI  - More information on patients with factor XI deficiency.

PMID- 15505484
TI  - An alternative to transtracheal injection for fiberoptic intubation in awake
      patients: a novel noninvasive technique using a standard multiorifice epidural
      catheter through the bronchoscope suction port.

PMID- 15505485
TI  - Society for Obstetric Anesthesia and Perinatology. Ft. Myers, Florida. May 12-16,
      2004.

PMID- 15505486
TI  - Immunohistochemical localization of cerebrovascular cannabinoid CB1 receptor
      protein.
AB  - Cannabinoids are powerful hypotensives and vasodilators. However, their mode of
      action is controversial. This study is the first to investigate the distribution
      of vascular CB1 receptor protein expression in situ. We used double-fluorescence
      and chromogenic immunohistochemistry to investigate patterns of CB1 protein
      expression in cerebrovascular tissue in rat brain sections. We found a layer of
      intense CB1 labeling immediately adjacent to the internal elastic lamina,
      consistent with myointimal and vascular smooth muscle cells, and diffuse labeling
      adventitial to this layer. We concluded that CB1 receptor are most intensely
      expressed in the vascular smooth muscle layer in cerebral arteries, and are
      likely to be chiefly responsible for the potent vasodilatory effect of
      cannabinoids.

PMID- 15505487
TI  - Effects of losartan and chlorthalidone on blood pressure and renal vascular
      resistance index in non-diabetic patients with essential hypertension and normal
      renal function.
AB  - Antihypertensive drugs can differ in target organ protection despite similar
      blood pressure (BP) control. We compared the effects of losartan (L) and
      chlorthalidone (C) on renal vascular resistance index (RVRI) in 194 grade I to
      II, non-diabetic hypertensive patients with increased RVRI (>0.68 m/s by echo
      Doppler) but normal renal function. Patients were randomly allocated to C 25 mg/d
      or L 50 mg/d according to a single blind, PROBE study design. After 4 weeks of
      treatment, 92 patients (48 L/44 C) with BP <140/90 mm Hg were enrolled in the
      long-term phase of the study. After 12 months a normalization of RVRI was
      observed in 47 of 48 patients treated with L (97.5%) and only in 14 of 44 of
      those treated with C (25.8%) despite no differences in BP control. Patients whose
      RVRI remained elevated during C therapy underwent a 2-week washout period and
      then were treated with L 50 mg/d for 12 additional months. After that period 28
      of 30 (95%) of patients who were nonresponders to C showed a normalization of
      RVRI despite no differences in BP control. In conclusion, our data suggest that
      treatment with L can improve renal hemodynamic and exert a protective renal
      effect beyond BP control in patients with hypertension.

PMID- 15505488
TI  - Altered vascular reactivity and KATP channel currents in vascular smooth muscle
      cells from deoxycorticosterone acetate (DOCA)-salt hypertensive rats.
AB  - This study was designed to evaluate the contribution of ATP-dependent potassium
      (KATP) channels to the changes in vascular reactivity and spontaneous tone
      observed in vessels isolated from deoxycorticosterone acetate (DOCA)-salt
      hypertensive rats. In phenylephrine preconstricted aortic rings, cromakalim
      induced concentration-dependent, glibenclamide-sensitive relaxation. The
      concentration response curve to cromakalim was shifted to the right in DOCA-salt
      hypertensive rats (EC50: 0.850 +/- 0.100 microM) compared with SHAM-normotensive
      rats (0.108 +/- 0.005 microM), and the maximum relaxation (Emax) evoked by
      cromakalim was significantly lower in aortic rings from the DOCA group (68 +/-
      2%) compared with the SHAM group (108 +/- 5%). The results were similar in
      endothelium-denuded rings. Spontaneous tone was observed in aortic rings (5 g
      preload) from DOCA-salt but not SHAM rats. Cromakalim abolished spontaneous tone
      and the effect was blocked by glibencamide. In whole cell patch clamp studies,
      increasing extracellular K concentrations from 5.4 to 140 mM and the
      administration of cromakalim evoked dramatic increases in KATP channel currents
      in aortic cells isolated from SHAM rats. In contrast, in aortic cells from DOCA
      salt hypertensive rats, KATP channel currents were either absent or weak in
      response to challenges by elevated extracellular K and by cromakalim. These
      findings suggest that the function of KATP channels is impaired in smooth muscle
      cells from aorta of DOCA-salt hypertensive rats, which may contribute to the
      impaired vasodilatation and spontaneous tone observed in these rats.

PMID- 15505489
TI  - Effect of isoproterenol on the cardiac troponin I degradation and release during
      early TNFalpha-induced ventricular dysfunction in isolated rabbit heart.
AB  - We studied the consequences of an early phase of TNFalpha-induced LV dysfunction
      and of its treatment by isoproterenol on an isolated rabbit heart preparation.
      Two dosages of TNFalpha (2 and 4 microg) were infused, followed by isoproterenol
      (ISO), infused by increasing concentrations from 10 to 10 M. Left ventricular
      developed pressure (DP) was recorded. Creatine kinase (CKtot) and cardiac
      Troponin I (cTnI) were measured in the effluent perfusate. An anatomic score was
      calculated by histologic examination of the hearts while a structural analysis of
      cTnI was done. TNFalpha induced a dose-dependent decrease in DP (-43 +/- 18% for
      4 microg) without change in coronary vascular resistances, which was not followed
      by biochemical or structural abnormalities. TNFalpha reduced the maximum effect
      (Emax) of ISO on DP (mean DeltaDPmaxISO = -40% for 4 microg) without change in
      the concentration leading to half Emax (ED50ISO). ISO treatment of TNFalpha (4
      microg)-induced LV dysfunction resulted in a selective release of cTnI,
      myocardial tissue contraction bands, and a significant proteolysis of cTnI.
      Within the limits of the model, the myocardial injury reported during severe
      sepsis would not be related to an early cytotoxic effect of TNFalpha but could be
      attributed to an enhancement of the effects of isoproterenol by TNFalpha.

PMID- 15505490
TI  - Inhibition of mitogen-mediated proliferation of rat vascular smooth muscle cells
      by labedipinedilol-A through PKC and ERK 1/2 pathway.
AB  - Labedipinedilol-A is a novel 1, 4-dihydropyridine type calcium antagonist with
      alpha-receptor blocking activity. This study investigates the effects of
      labedipinedilol-A on mitogen-induced proliferation of rat vascular smooth muscle
      cells (VSMCs). Labedipinedilol-A's inhibition on cell proliferation was measured
      by the tetrazolium salt (XTT) test. Labedipinedilol-A dose-dependently inhibited
      mitogen-induced DNA synthesis, determined by the incorporation of 5-bromo-2'
      deoxyuridine (BrdU). Labedipinedilol-A was also found capable of inhibiting the
      migration of VSMCs induced by PDGF-BB with an IC50 value of 5.6 microM. In
      accordance with these findings, labedipinedilol-A revealed blocking of the FBS
      inducible progression through G0/G1 to S phase of the cell cycle in synchronized
      cells. Labedipinedilol-A appeared to cause inhibition of mitogens-induced PKC
      translocation, suggesting the probable involvement of protein kinase C (PKC) in
      this cellular response. Labedipinedilol-A reduced both intracellular Ca and the
      phosphorylation of extracellular signal-regulated protein kinase 1/2 in PDGF-BB
      stimulated VSMCs. It also suppressed the levels of proliferative cell nuclear
      antigen (PCNA) in VSMCs both time- and dose-dependently. These results indicate
      that labedipinedilol-A may inhibit cell proliferation by attenuating activation
      of the ERK 1/2 pathway, which is regulated by PKC and Ca, suggesting that it may
      have great potential in the prevention of progressive atherosclerosis.

PMID- 15505491
TI  - Important role of superoxide dismutase in EDHF-mediated responses of human
      mesenteric arteries.
AB  - The endothelium synthesizes and releases several vasodilator substances,
      including prostacyclin, nitric oxide (NO), and endothelium-derived
      hyperpolarizing factor (EDHF). We have identified hydrogen peroxide (H2O2) as an
      EDHF in mouse and human mesenteric arteries and porcine coronary microvessels. We
      also have recently demonstrated that Cu,Zn-SOD plays an important role in EDHF
      synthesis in mouse mesenteric arteries. However, it remains to be determined
      whether SOD also plays an important role in EDHF-mediated responses of human
      arteries. In this study, we addressed this point in human mesenteric arteries. We
      used small mesenteric arteries of patients who underwent gastrectomy operations.
      Isometric tensions and membrane potentials were recorded in the presence of
      indomethacin and N-nitro-L-arginine to inhibit the synthesis of prostacyclin and
      NO, respectively. Pretreatment with Tiron, a cell-permeable SOD-mimetic,
      significantly enhanced the EDHF-mediated relaxations and hyperpolarizations to
      bradykinin, and this effect was abolished by catalase, indicating that this
      enhancing effect was achieved by H2O2. By contrast, Tiron did not affect
      endothelium-independent relaxations, indicating that the enhancing effect of
      Tiron is not caused by the enhancement of vascular smooth muscle responses. These
      results indicate that SOD plays an important role in EDHF-mediated relaxations
      and hyperpolarizations of human mesenteric arteries.

PMID- 15505492
TI  - Endothelial nitric oxide synthase-independent effects of an ACE inhibitor on
      coronary flow response to bradykinin in aged mice.
AB  - ACE inhibitors are known to ameliorate cardiovascular complications in aging;
      however, their effects on the coronary circulation in relation to aging and eNOS
      dependence remain to be examined. Coronary flow responses to bradykinin with or
      without ACE inhibitors were examined in Langendorff-perfused hearts from young
      (16-20 weeks) and aged (16-20 months) control and eNOS mice. Western blot
      analysis was performed for cardiac eNOS, nNOS, and ACE. Baseline coronary flow
      was comparable between young and aged mice of both strains. Aging did not affect
      bradykinin-induced coronary flow in either strain. Interestingly, both acute and
      chronic treatment with an ACE inhibitor markedly augmented the flow response in
      aged control and eNOS mice. Aged eNOS mice were markedly hypertensive and had
      larger ventricular mass than control mice. The antihypertensive effect of
      temocapril was greater in aged eNOS mice, associated with reduction in the
      ventricular weight in both strains. Western blot analysis demonstrated an
      increased expression of eNOS in aged control mice, and ACE expression was
      increased in eNOS mice. These results indicate that coronary flow response to
      bradykinin is preserved in aged mice even in the absence of eNOS, and an ACE
      inhibitor augments this response by both eNOS-dependent and -independent
      mechanisms.

PMID- 15505493
TI  - Effects of acute systemic endothelin receptor blockade on cardiac
      electrophysiology in vivo.
AB  - BQ-123, a selective endothelin-A receptor antagonist, has been demonstrated to
      suppress arrhythmias. However, the role of physiologic levels of endogenous
      endothelin-1 (ET-1) with respect to electrophysiologic properties of the heart is
      unknown. BQ-123 (0.45, 0.9, 1.8, 3.6, 7.2, and 14.4 microg/kg/min; n = 10) or
      saline (control, n = 5) was administered IV for 15 minutes of continuous-rate
      infusion at incremental doses to anesthetized normal pigs. BQ-123 had no effect
      on PR and QT interval, QRS duration, intraatrial and AV nodal conduction time as
      well as the atrial, AV nodal, and ventricular effective refractory periods. As
      compared with baseline, BQ-123 at 7.2 and 14.4 microg/kg/min caused an increase
      in heart rate (99 +/- 17 versus 110 +/- 14 and 118 +/- 14 bpm, respectively; P <
      0.05), shortened sinus node recovery time (818 +/- 165 versus 641 +/- 69 and 609
      +/- 74 milliseconds, respectively; P < 0.05) and decreased mean arterial pressure
      at 14.4 microg/kg/min (95 +/- 18 versus 80 +/- 11 mm Hg; P < 0.05). We conclude
      that in the normal pig, physiologic levels of ET-1 have no effect on conduction
      properties of atrial, AV nodal, or Purkinje fibers. However, antagonism of ET-1
      by BQ-123 unmasks the effect of ET-1 on maintenance of vasomotor tone, which in
      turn may affect heart rate and sinus node automaticity in the intact pig.

PMID- 15505494
TI  - The abnormal renal vasodilator response to D1-like receptor stimulation in
      conscious SHR can be normalized by AT1 blockade.
AB  - BACKGROUND: We previously showed that the renal vasodilator response to a D1-like
      receptor agonist is blunted in conscious SHR compared with WKY rats. The
      mechanism of this impaired dopaminergic responsiveness in SHR is unclear. An
      altered balance between the renin-angiotensin-aldosterone system (RAAS) and the
      dopaminergic system may be involved. To determine the interaction between the
      RAAS and the dopaminergic system in the blunted D1-like responsiveness in SHR, we
      studied the renal vasodilator response to the D1-like receptor agonist fenoldopam
      before and after 7 days of pretreatment with the AT1-receptor antagonist (AT1-A)
      L158,809 in conscious SHR and WKY rats. METHODS: Effective renal plasma flow
      (ERPF) was measured by the clearance of I-hippuran. Mean arterial pressure (MAP)
      was measured via an intraarterial catheter. RESULTS: Without pretreatment, MAP
      was reduced to comparable degrees by fenoldopam in WKY (-7 +/- 4%, ns) and SHR (
      6 +/- 1%, P < 0.05). However, ERPF was significantly more increased (P < 0.006)
      by fenoldopam in WKY (+26 +/- 2%, P < 0.0001) than in SHR (+2 +/- 2%, ns). AT1-A
      treatment reduced MAP and increased ERPF and glomerular filtration rate
      significantly in both strains. Pretreatment with AT1-A significantly potentiated
      the fenoldopam-induced rise in ERPF in SHR, but not in WKY, without affecting the
      blood pressure responses in either strain. As a result, during pretreatment with
      an AT1-A, the rise in ERPF by fenoldopam was similar in both strains (SHR +25 +/-
      2%, P < 0.0001; WKY +33 +/- 2%, P < 0.0001). CONCLUSIONS: These results suggest
      that the RAAS accounts for the blunted renal vasodilator response to a D1-like
      receptor agonist in SHR. A dysbalance between the dopaminergic system and the
      RAAS may be involved in the abnormal renal hemodynamic regulation in SHR.

PMID- 15505495
TI  - Human urotensin II modulates collagen synthesis and the expression of MMP-1 in
      human endothelial cells.
AB  - OBJECTIVES: Human urotensin II (hU-II) is a cyclic peptide highly expressed in
      cardiac tissues and blood vessels. hU-II is a potent vasoconstrictor. Recent
      studies indicate that urotensin II participates in myocardial remodeling after
      injury. This study was designed to study the role of hU-II in the expression of
      matrix metalloproteinase-1 (MMP-1) and collagen-1 in human umbilical vein
      endothelial cells (HUVECs) and underlying intracellular signaling mechanisms.
      METHODS AND RESULTS: Cultured HUVECs were incubated with hU-II (10 to 80 nM) for
      3 to 24 hours. hU-II increased the expression (mRNA and protein) of collagen-1 in
      a concentration- and time-dependent manner. In contrast, hU-II decreased the
      expression and activity of MMP-1. Further, hU-II caused the phosphorylation of
      mitogen-activated protein kinase p42/44 (MAPKp42/44). This effect of hU-II was
      inhibited by pretreatment of cells with the MEK inhibitor (PD98059, 10 microM).
      In addition, treatment of cells with PD98059 attenuated protein expression of
      collagen-1 and MMP-1 elicited by hU-II (P < 0.01 versus hU-II alone).
      CONCLUSIONS: Our observations provide evidence that hU-II modulates the
      expression of MMP-1 and collagen-1 in HUVECs, and MAPKp42/44 activation may play
      a signal transduction role in this process.

PMID- 15505497
TI  - Inhibition of cardiac mitochondrial respiration by salicylic acid and
      acetylsalicylate.
AB  - Acetylsalicylate, the active ingredient in aspirin, has been shown to be
      beneficial in the treatment and prevention of cardiovascular disease. Because of
      the increasing frequency with which salicylates are used, it is important to more
      fully characterize extra- and intracellular processes that are altered by these
      compounds. Evidence is provided that treatment of isolated cardiac mitochondria
      with salicylic acid and to a lesser extent acetylsalicylate resulted in an
      increase in the rate of uncoupled respiration. In contrast, both compounds
      inhibited ADP-dependent NADH-linked (state 3) respiration to similar degrees.
      Under the conditions of our experiments, loss in state 3 respiration resulted
      from inhibition of the Krebs cycle enzyme alpha-ketoglutarate dehydrogenase
      (KGDH). Kinetic analysis indicates that salicylic acid acts as a competitive
      inhibitor at the alpha-ketoglutarate binding site. In contrast, acetylsalicylate
      inhibited the enzyme in a noncompetitive fashion consistent with interaction with
      the alpha-ketoglutarate binding site followed by enzyme-catalyzed acetylation.
      The effects of salicylic acid and acetylsalicylate on cardiac mitochondrial
      function may contribute to the known cardioprotective effects of therapeutic
      doses of aspirin, as well as to the toxicity associated with salicylate overdose.

PMID- 15505496
TI  - Effect of chronic exercise and Angiotensin-converting enzyme inhibition on rodent
      thoracic aorta.
AB  - Vascular reactivity can be modulated by local physical factors as well as
      pharmacologic manipulations. The aim of this study was to evaluate the effects of
      chronic exercise (EX) with or without the ACEI captopril (CAP) on vascular
      reactivity. Sixty-four Sprague-Dawley male rats were randomized into 4 groups (n
      = 16): group 1, control; group 2, captopril; group 3, exercise; and group 4,
      exercise and captopril. After 10 weeks of treatment, rats were killed, and their
      thoracic aortas harvested. Vascular reactivity was studied in an organ chamber (n
      = 12). Aortic endothelium constitutive nitric oxyde synthase (NOS3) expression
      was determined by Western blot analysis (n = 4). Endothelial-dependent relaxation
      was increased in both CAP and EX rats relative to the control group. Maximal
      aortic relaxations were enhanced in the CAP group, and potencies of these
      mediators were enhanced in the EX group (P < 0.05 versus control). Combined
      treatment did not result in a synergistic effect. NOS3 relative expressions were:
      group 1, 100%; group 2, 241%; group 3, 64%; and group 4, 108%. Exercise enhanced
      both potencies and efficacies of the mediators studied, whereas CAP increased
      mainly their efficacies. NOS3 protein expression was up-regulated in CAP-treated
      rats but not in exercised rats. These findings suggest different mechanisms for
      the observed increased vascular reactivity.

PMID- 15505498
TI  - Long-term treatment with a phosphodiesterase type 5 inhibitor improves pulmonary
      hypertension secondary to heart failure through enhancing the natriuretic
      peptides-cGMP pathway.
AB  - In advanced heart failure (HF), the compensatory pulmonary vasodilation is
      attenuated due to the relative insufficiency of cGMP despite increased secretion
      of natriuretic peptides (NPs). Phosphodiesterase type 5 (PDE5) inhibitors prevent
      cGMP degradation, and thus may potentiate the effect of the NPs-cGMP pathway. We
      orally administered a specific PDE5 inhibitor, T-1032 (1 mg/kg; twice a day, n =
      7) or placebo (n = 7) for 2 weeks in dogs with HF induced by rapid pacing (270
      bpm, 3 weeks) and examined the plasma levels of atrial natriuretic peptide (ANP),
      cGMP, and hemodynamic parameters. We also examined the hemodynamic changes after
      injection of a specific NPs receptor antagonist, HS-142-1 (3 mg/kg), under
      treatment with T-1032. T-1032 significantly increased plasma cGMP levels compared
      with the vehicle group despite low plasma ANP levels associated with improvement
      in cardiopulmonary hemodynamics. HS-142-1 significantly decreased plasma cGMP
      levels in both groups, whereas it did not change all hemodynamic parameters in
      the vehicle group. In contrast, in the T-1032 group, HS-142-1 significantly
      increased pulmonary arterial pressure and pulmonary vascular resistance. These
      results indicated that long-term treatment with a PDE5 inhibitor improved
      pulmonary hypertension secondary to HF and the NPs-cGMP pathway contributed to
      this therapeutic effect.

PMID- 15505499
TI  - Continuous therapy with nitroglycerin impairs endothelium-dependent vasodilation
      but does not cause tolerance in conductance arteries: a human in vivo study.
AB  - We investigated in healthy humans whether continuous therapy with organic
      nitrates impairs conduit artery responses to nitroglycerin (GTN) as well as its
      effects on endothelium-dependent vasodilation. Sixteen young male volunteers were
      randomized to continuous treatment with either transdermal GTN (0.6 mg/h/24 hrs
      for 6 days) or no therapy. Endothelium-dependent (flow-mediated) dilatation (FMD)
      and endothelium-independent (GTN-mediated) dilatation (GMD) of the brachial
      artery were evaluated before randomization (session 1), after six days of
      transdermal GTN treatment (session 2), and three hours after withdrawal of
      transdermal GTN (session 3). In the GTN group, on session 1, 0.4 mg sublingual
      GTN increased resting brachial artery diameter from 0.40 +/- 0.03 to 0.45 +/-
      0.03 cm (P < 0.01). At the time of session 2, this GTN-mediated vasodilation
      remained unchanged at baseline (0.47 +/- 0.04 cm), with no further significant
      dilatation in response to either stimulus. On session 3, three hours after patch
      removal, baseline brachial artery diameter and GMD returned to pretreatment
      values, but FMD remained blunted (session 1: 8.7 +/- 2.5; session 3: 4.1 +/-
      1.7%, P < 0.05). There was no change in these variables in the control group. Our
      data demonstrate that continuous GTN therapy impairs endothelium-dependent
      vasodilation in conduit arteries yet does not induce nitrate tolerance.

PMID- 15505500
TI  - Low-density lipoprotein inhibits receptor-mediated prostaglandin synthesis
      without affecting calcium and arachidonic acid mobilization in human endothelial
      cells.
AB  - Vascular serotonin 5-HT1 receptors have quiescent constrictor activity that is
      activated by other vasoactive agents such as histamine. Previously, we observed
      that the 5-HT1-selective agonist 5-carboxamidotryptamine (5-CT) potentiated
      histamine-stimulated arachidonic acid (AA) mobilization and prostaglandin
      production in human aortic endothelial cells (HAEC). In the present study, 5-CT
      was found to potentiate histamine-stimulated calcium mobilization but had no
      effect on intracellular calcium when added alone. Treatment of HAEC with human
      low-density lipoprotein (LDL) for 20 hours inhibited the histamine- plus 5-CT
      stimulated production of prostaglandin F2alpha (PGF2alpha) and the prostacyclin
      metabolite 6-keto-PGF1alpha. However, the effects of histamine and histamine
      potentiation by 5-CT on intracellular Ca mobilization and AA release were
      resistant to LDL treatment. Conversely, the subsequent receptor-independent
      conversion of AA to prostaglandins was inhibited by LDL. These results
      demonstrate that histamine and serotonin receptor activity, measured as the
      stimulation of Ca and AA mobilization, is resistant to LDL exposure under mild
      oxidizing conditions, whereas the receptor-independent synthesis of
      prostaglandins is inhibited by LDL. The results also suggest that the LDL
      stimulated mobilization of cellular AA is responsible for the LDL-mediated
      inhibition of prostaglandin synthesis. These findings suggest a mechanism by
      which LDL and/or atherosclerosis could promote the vascular liberation of AA that
      is not converted to endothelium-derived prostaglandins and is therefore available
      as substrate for the production of other eicosanoids.

PMID- 15505501
TI  - Vascular endothelial growth factor-induced nitric oxide- and PGI2-dependent
      relaxation in human internal mammary arteries: a comparative study with KDR and
      Flt-1 selective mutants.
AB  - The role of the vascular endothelial growth factors (VEGF) receptors (KDR and Flt
      1) and their characteristics in VEGF-induced vasodilation in human vessels is
      unclear. This study investigated the in vitro vasorelaxant effects of KDR
      selective (KDR-SM) and Flt-1-selective mutants (Flt-1-SM) in the human internal
      mammary artery (IMA). IMA segments (n = 183) taken from 48 patients were studied
      in organ baths. The cumulative concentration (-12 to -8 log10M)-relaxation curves
      were established for VEGF, KDR-SM, Flt-1-SM, and placenta growth factor (PlGF) in
      the absence or presence of indomethacin (INDO, 7 microM), N-nitro-L-arginine (L
      NNA, 300 microM), L-NNA + oxyhemoglobin (HbO, 20 microM), or INDO + L-NNA + HbO.
      The VEGF-induced relaxation was abolished in endothelium-denuded IMA. In the
      endothelium-intact vessel rings, VEGF (63.2 +/- 3.9%) induced significantly more
      (P < 0.001) relaxation than Flt-1-SM (28.5 +/- 4.3%, 95% CI 18.1-51.3%), and PlGF
      (26.0 +/- 4.7%, 95% CI 17.6-56.8%). The maximal relaxation induced by KDR-SM
      (53.0 +/- 4.0%) was only slightly less than that by VEGF (P = 0.075) but
      significantly more than that by Flt-1-SM (P = 0.001, 95% CI 7.8-41.1%).
      Pretreatment of INDO or L-NNA + HbO significantly (P < 0.001) inhibited the
      relaxation by VEGF (21.2 +/- 3.9% or 23.3 +/- 4.3%) and KDR-SM (9.8 +/- 8.2% or
      10.1 +/- 17.8%). INDO + L-NNA + HbO completely inhibited the relaxation by VEGF,
      KDR-SM, or Flt-1-SM. KDR may be the dominant receptor in mediating the VEGF
      mediated relaxation, which is regulated by both PGI2 and nitric oxide but
      probably not by endothelium-derived hyperpolarizing factor, in the human IMA.
      This study gives insight into the characteristics of the VEGF-mediated
      vasodilation and provides a scientific basis for potential clinical application
      of VEGF/KDR-SM in ischemic heart disease.

PMID- 15505502
TI  - Comparision of the inotropic effects of levosimendan, rolipram, and dobutamine on
      human atrial trabeculae.
AB  - The aim of this study was to compare the positive inotropic effects of 3
      different agents with 3 different mechanisms of actions-levosimendan, rolipram,
      and dobutamine-on human atrial trabecular muscles. Samples of right atrial
      appendage (1 cm, 500-1000 mg) were removed and immersed in preoxygenated and
      modified Tyrode solution. In oxygenated Tyrode solution, preparations were used
      to investigate the concentration-effect relationship of levosimendan, dobutamine,
      and rolipram on percentage developed tension (DT), from 10 to 10 M, each
      concentration for 15 minutes. All 3 agents produced concentration-dependent
      increments in DT. We found that levosimendan was the most efficacious positive
      inotropic agent on isolated human atrial trabeculae. Both the sensitivity (pD2)
      and maximum response (Emax) of human atrial trabeculae to levosimendan (6.711 +/-
      0.26 and 23.2 +/- 2.2 mN, respectively) were significantly greater than those of
      dobutamine (6.663 +/- 0.19 and 17.6 +/- 2.8 mN) and rolipram (6.497 +/- 0.18 and
      15.0 +/- 1.0 mN). pD2 and Emax values for dobutamine were significantly higher
      than those for rolipram. It was suggested that because of its potential to
      enhance cardiac performance without predisposition to calcium-induced
      arrhythmias, levosimendan might be more useful as a positive inotropic agent in
      clinical practice.

PMID- 15505503
TI  - Levels of evidence for the outcome of endodontic retreatment.
AB  - The purpose of this investigation was 2-fold: (a) to complete a thorough search
      of published literature related to clinical studies on the success and failure of
      nonsurgical retreatment, and (b) to assign levels of evidence to these
      publications. Clinical studies related to success and failure of retreatment
      since 1970 were identified using both electronic and manual literature searches.
      After identification of pertinent literature, each article received a level of
      evidence (LOE) from one (high) to five (low). Thirty-one clinical studies and six
      review articles related to this subject were identified. There was no LOE 1
      Randomized Control Trials (RCT). There were three LOE 2 RCTs, one LOE 2 Cohort,
      and two LOE 3 Case Control Studies. Thirteen Case Series (LOE 4), which comprise
      the most highly quoted success and failure data, were found. Twelve Case Reports
      (LOE 5) and six review articles (LOE 5) were found. Based on these findings, it
      appears that few high level studies have been published in the past 34 yr related
      to the success and failure of endodontic retreatment.

PMID- 15505504
TI  - Treatment outcome in endodontics-The Toronto Study. Phases I and II: apical
      surgery.
AB  - This study prospectively assessed the 4 to 8 yr outcome of apical surgery
      performed by graduate students in phases I and II of the Toronto Study. The study
      cohort included 155 teeth in 138 patients. Outcome was assessed by a blinded and
      calibrated examiner. Clinical and radiographic measures were used for a
      dichotomous outcome: healed (no signs and symptoms, Periapical Index score </= 2
      or scar), or diseased (presence of signs and symptoms, or Periapical Index score
      >/= 3). The recall rate was 85% and the overall healed rate 74%. Healed rate was
      significantly higher for teeth with small (</= 5 mm) than larger preoperative
      lesions (chi, p = 0.02). Logistic Regression revealed an increased odds of
      disease persistence for teeth with larger preoperative lesions (OR = 3.81, CI =
      1.2-12.1), and preoperative root-filling of adequate length (OR = 3.7, CI = 1.1
      11.1). Preoperative lesion size and root-filling length were significant
      predictors of outcome of apical surgery.

PMID- 15505505
TI  - Evaluation of periapical lesion healing by correction of gray values.
AB  - The purpose of this study was to compare two methods for evaluating periapical
      healing in humans: the periapical index (PAI) and a gray value correction method.
      Fifty human teeth with a periapical lesion were endodontically treated.
      Radiographs, with a special aluminum device, were taken postoperatively, after 3
      months and after 6 months. The PAI was recorded at each period of time, and a
      Kruskall and Wallis test was performed to compare the three groups. After
      scanning, the size of the lesion and its gray value were recorded. The aluminum
      device allowed the gray values to be equalized. An analysis of variance followed
      by a Duncan test was performed to compare the three groups. The teeth that showed
      no sign of healing according to the PAI were separately analyzed by an analysis
      of variance and a Duncan test. The PAI (n = 50) showed signs of periapical
      healing over time (p < 0.01). The analysis of variance, based on gray value
      evaluation (n = 50), also showed signs of periapical healing over time (p <
      0.002). The analysis of variance of teeth with the same PAI over time (n = 15 at
      3 months, and n = 5 at 6 months), based on gray value evaluation showed
      statistically significant differences among the 3 groups (p < 0.02). These
      results show that the gray level correction method is powerful and may reduce the
      risks of false negative responses during assessment of treatment results or
      epidemiological studies.

PMID- 15505506
TI  - Expression of insulin-like growth factor-1 receptor in human pulp tissue.
AB  - Insulin-like growth factor-1 (IGF-1) plays an important role in cell
      proliferation and differentiation. The purpose of this study was to use a
      radioreceptor assay to evaluate whether IGF-1 receptors are present in human pulp
      and to determine whether differences in its expression are found in the pulp
      tissue of teeth having incomplete or complete root development. Twenty pulps were
      obtained from freshly extracted human third molars; they were then processed and
      labeled with I-IGF-1. The results showed IGF-1 receptor expression in all human
      pulp samples. t test revealed statistically significant higher expression in the
      pulps from teeth having incomplete root development (P <0.005). Given the
      functions of this growth factor system in other tissues, the present findings are
      consistent with the hypothesis that IGF-1 contributes toward forming and
      mineralizing dental tissues as well as in pulp-repairing processes.

PMID- 15505507
TI  - Substance P enhances expression of lipopolysaccharide-induced inflammatory
      factors in dental pulp cells.
AB  - To examine how substance P (SP) is related with dental pulp inflammation, we
      examined the effects of SP on expression of genes for inflammatory factors in
      human dental pulp cell cultures. Using reverse transcriptase-polymerase chain
      reaction, we found that Prevotella intermedia lipopolysaccharide (LPS) induced
      expression of SP and SP-receptor mRNAs, and that somatostatin inhibited the LPS
      induced expression of SP mRNA. We also found that SP enhanced LPS-induced
      stimulation of NF-kappaB binding activity. In addition, SP induced expression of
      cyclooxygenase-2 and interleukin-10 receptor mRNAs. In contrast, SP inhibited
      expression of interferon-gamma receptor mRNA. These results suggest that SP may
      play a regulatory role in the immunological response of dental pulp tissue to
      pathogenic bacteria.

PMID- 15505508
TI  - A comparison of the in vitro retentive strength of glass-ionomer cement, zinc
      phosphate cement, and mineral trioxide aggregate for the retention of
      prefabricated posts in bovine incisors.
AB  - The purpose of this study was to compare the retentive strength of zinc-phosphate
      cement, glass-ionomer cement, and mineral trioxide aggregate (MTA) cement in the
      retention of prefabricated posts. The root canals of 60 bovine incisors were
      prepared and obturated with warm gutta-percha. Post space was prepared, the smear
      layer removed, and posts were luted with zinc-phosphate cement, glass-ionomer
      cement, or MTA. The specimens were stored at 37 degrees C and 100% humidity for 2
      weeks, and then subjected to increasing axial tensile forces by an Instron
      machine until bond failure occurred. Data were analyzed by a one-way ANOVA and a
      Tukey-Kramer multiple comparison test. The retentive strengths of zinc phosphate
      and glass-ionomer cements were statistically equivalent, and significantly
      greater than MTA (p < 0.001), which suggests that zinc phosphate or glass-ionomer
      cement may be superior to MTA when used as luting agents for posts in
      endodontically treated teeth.

PMID- 15505509
TI  - Antimicrobial effect of ozonated water on bacteria invading dentinal tubules.
AB  - Ozone is known to act as a strong antimicrobial agent against bacteria, fungi,
      and viruses. In the present study, we examined the effect of ozonated water
      against Enterococcus faecalis and Streptcoccus mutans infections in vitro in
      bovine dentin. After irrigation with ozonated water, the viability of E. faecalis
      and S. mutans invading dentinal tubules significantly decreased. Notably, when
      the specimen was irrigated with sonication, ozonated water had nearly the same
      antimicrobial activity as 2.5% sodium hypochlorite (NaOCl). We also compared the
      cytotoxicity against L-929 mouse fibroblasts between ozonated water and NaOCl.
      The metabolic activity of fibroblasts was high when the cells were treated with
      ozonated water, whereas that of fibroblasts significantly decreased when the
      cells were treated with 2.5% NaOCl. These results suggest that ozonated water
      application may be useful for endodontic therapy.

PMID- 15505510
TI  - Bacterial leakage with mineral trioxide aggregate or a resin-modified glass
      ionomer used as a coronal barrier.
AB  - The purpose of this study was to evaluate gray mineral trioxide aggregate (MTA),
      white MTA, and Fuji II LC cement as coronal barriers to bacterial leakage.
      Seventy-eight, matched, human teeth were obturated with gutta-percha. In group I,
      18 pairs received a 3-mm barrier of gray or white MTA. In group II, 18 pairs
      received a 3-mm barrier of gray MTA or Fuji cement. Three pairs were used as
      positive (obturated without barrier) and negative (covered with epoxy resin)
      controls. A dual-chamber leakage model utilizing salivary microbes was used for
      the evaluation. Leakage was recorded when turbidity was observed. All controls
      behaved as expected. In group I, three gray MTA and three white MTA samples
      leaked. In group II, one gray MTA and three Fuji samples leaked. There was no
      statistically significant difference in leakage between gray and white MTA or
      gray MTA and Fuji at 30, 60, or 90 days. Gray and white MTA or Fuji II can be
      recommended as a coronal barrier for up to 3 months.

PMID- 15505511
TI  - Soft tissue dissolution capacity of currently used and potential endodontic
      irrigants.
AB  - Necrotic soft-tissue remnants in root canals may provide a source of nutrition
      for surviving microbiota after root-canal therapy. This study assessed the
      necrotic tissue dissolution capacity of some popular and some potential root
      canal irrigants: 1% (wt/vol) sodium hypochlorite (NaOCl), 10% chlorhexidine, 3%
      and 30% hydrogen peroxide, 10% peracetic acid, 5% dichloroisocyanurate (NaDCC),
      and 10% citric acid. Standardized necrotic tissue samples obtained from pig
      palates were incubated in these solutions, and their weight loss was measured
      over time. None of the test solutions except sodium hypochlorite had any
      substantial tissue dissolution capacity. It was concluded that this might be
      important when considering the use of irrigants other than NaOCl.

PMID- 15505512
TI  - Effect of 2% chlorhexidine gel as an intracanal medication on the apical seal of
      the root-canal system.
AB  - The purpose of this study was to determine what effect intracanal medications
      might have on the apical seal of the root-canal system. Forty-two teeth were
      cleaned and shaped in a crown-down manner to a size #50 K-file. The teeth were
      divided into three groups: (A) immediate obturation; (B) intracanal placement of
      calcium hydroxide placed for 14 days; and (C) 2% chlorhexidine gel placed for 14
      days. After 14 days, these materials were removed using copious irrigation and
      obturation was completed on groups B and C. Obturation was performed using the
      continuous wave of condensation technique using AH Plus sealer in all groups.
      Leakage was evaluated 60 days after obturation by using a fluid-filtration
      device. Using the one-way ANOVA test, there was no statistically significant
      difference in leakage between the three groups. Under the conditions of this
      study, 2% chlorhexidine gel and calcium hydroxide paste did not adversely affect
      the apical seal of the root-canal system.

PMID- 15505513
TI  - Evaluation of the effect of endodontic irrigation solutions on the microhardness
      and the roughness of root canal dentin.
AB  - The purpose of this study was to evaluate the effect of 0.2% chlorhexidine
      gluconate on the microhardness and roughness of root canal dentin compared with
      widely used irrigation solutions. Ninety, mandibular, anterior teeth extracted
      for periodontal reasons were used. The crowns of the teeth were removed at the
      CEJ. The roots were separated longitudinally into two segments, embedded in
      acrylic resin, and polished. A total of 180 specimens were divided into 6 groups
      of 30 teeth at random according to the irrigation solution used: group 1: 5.25%
      NaOCl for 15 min; group 2: 2.5% NaOCl for 15 min; group 3: 3% H2O2 for 15 min;
      group 4: 17% EDTA for 15 min; group 5: 0.2% chlorhexidine gluconate for 15 min;
      and group 6: distilled water (control). Each group was then divided into 2
      subgroups of 15 specimens: groups 1a, 2a, 3a, 4a, 5a, and 6a were submitted to
      Vickers microhardness indentation tests; groups 1b, 2b, 3b, 4b, 5b, and 6b were
      used for determination of the roughness of root dentin. The data were recorded as
      Vickers numbers and Ra, microm for roughness test. The results were analyzed
      statistically by using one-way ANOVA and Tukey tests. The results indicated that
      all the irrigation solutions except chlorhexidine significantly decreased
      microhardness of root canal dentin (p < 0.05); 3% H2O2 and 0.2% chlorhexidine
      gluconate had no effect on roughness of the root canal dentin (p > 0.05).
      Although there are many other factors for irrigation solution preference,
      according to the results of this study, 0.2% chlorhexidine gluconate seems to be
      an appropriate endodontic irrigation solutions because of its harmless effect on
      the microhardness and roughness of root canal dentin.

PMID- 15505514
TI  - Treatment of periapical inflammatory lesion with the combination of platelet-rich
      plasma and tricalcium phosphate: a case report.
AB  - Periapical surgery is an important treatment alternative in the presence of a
      periapical inflammatory lesion. To achieve optimal healing and regeneration of
      the bone, different bone substitutes or barrier membranes can be used after
      degranulation of the lesion. Tricalcium phosphate (TCP) graft material is one of
      these substitutes. Platelet Rich Plasma (PRP) preparation is a new biotechnology
      and can be used in many different surgical procedures. It consists of thrombocyte
      concentrates and high amounts of growth factors (GFs), especially platelet
      derived growth factor (PDGF), insulin-like growth factor (IGF-I) and transforming
      growth factor (TGF-beta), which are important in wound healing and regeneration.
      In this case report, use of platelet gel in conjunction with TCP in the treatment
      of periapical inflammatory lesion and the results of 12 months has been reported.

PMID- 15505516
TI  - Reasoning in believers in the paranormal.
AB  - Reasoning biases have been identified in deluded patients, delusion-prone
      individuals, and believers in the paranormal. This study examined content
      specific reasoning and delusional ideation in believers in the paranormal. A
      total of 174 members of the Society for Psychical Research completed a delusional
      ideation questionnaire and a deductive reasoning task. The reasoning statements
      were manipulated for congruency with paranormal beliefs. As predicted,
      individuals who reported a strong belief in the paranormal made more errors and
      displayed more delusional ideation than skeptical individuals. However, no
      differences were found with statements that were congruent with their belief
      system, confirming the domain-specificity of reasoning. This reasoning bias was
      limited to people who reported a belief in, rather than experience of, paranormal
      phenomena. These results suggest that reasoning abnormalities may have a causal
      role in the formation of unusual beliefs. The dissociation between experiences
      and beliefs implies that such abnormalities operate at the evaluative, rather
      than the perceptual, stage of processing.

PMID- 15505517
TI  - Schizophrenia and the cultural epidemiology of stigma in Bangalore, India.
AB  - Illness-related stigma is a complex and important issue, and its social impact
      contributes to a hidden burden of many health problems. Mitigating effects of
      stigma are a priority for mental health policy, especially for schizophrenia.
      Although numerous studies document its impact on patients and their families,
      health studies of stigma typically regard it in global terms without adequate
      attention to the conceptual and practical importance of sociocultural contexts
      and the particular features of illness that evoke stigma. Research at a
      psychiatric referral center in Bangalore, India, studied the cultural
      epidemiology of schizophrenia and stigma in interviews with family caretakers of
      60 patients, using a locally adapted EMIC interview and the Positive and Negative
      Symptom Scale. An index of 13 stigma queries based on Goffman's formulation
      covered relevant aspects and proved to be internally consistent (Cronbach alpha =
      0.81). Multivariate statistical regression and qualitative analysis of narratives
      were used to analyze this stigma index and identify explanatory variables based
      on cultural patterns of distress (PD), perceived causes (PC), and previous help
      seeking (HS). Significant variables included suspiciousness and inappropriate
      sexual behavior (PD), heredity and bad deeds (PC), and informal help seeking
      (HS). Previous allopathic help seeking was negatively associated with stigma.
      Analysis of coded text segments from respondent narratives showed how these
      variables were related to family-perceived stigma, with reference to marriage
      practices, moral meanings of schizophrenia, and ways in which effective
      allopathic care minimized stigma. Findings identify features of schizophrenia
      related stigma in India, contribute to comparative culture studies, and inform
      practical approaches to mitigate stigma through community awareness and improved
      mental health services.

PMID- 15505518
TI  - Negative symptoms, trauma, and autobiographical memory: an investigation of
      individuals recovering from psychosis.
AB  - Psychological research on negative symptoms in schizophrenia is scarce. The aim
      of this study was to explore the relationship between negative symptoms and
      trauma in individuals recovering from a psychotic illness. Specifically, the aim
      was to examine the association between negative symptoms and traumatic reactions
      to psychosis and to hospitalization. We were also interested in the association
      between traumatic reactions and autobiographical memory. The design was a cross
      sectional investigation of 38 people recovering from functional psychotic
      illness. Hypotheses were examined using correlations between measures of negative
      symptoms, posttraumatic avoidance, and specificity of autobiographical retrieval.
      Negative symptoms were found to be significantly associated with avoidance of
      traumatic memories related to psychosis and hospitalization and with a lack of
      specificity in autobiographical recall. Further analysis showed that avoidance
      related to psychosis and low specificity in recall were significant predictors of
      negative symptoms. These data suggest that people who avoid traumatic memories of
      psychosis and hospitalization have more negative symptoms and retrieve fewer
      specific autobiographical memories. The possibility that negative symptoms may be
      reactive is explored, along with the implications for our theoretical and
      clinical understanding. The methodological limitations of the study and ideas for
      future research are discussed.

PMID- 15505519
TI  - The role of experiential avoidance in posttraumatic stress symptoms and symptoms
      of depression, anxiety, and somatization.
AB  - This study examined the relationships between experiential avoidance in general
      (and thought suppression in particular), posttraumatic stress symptom severity,
      and symptoms of depression, anxiety, and somatization among a sample of
      individuals exposed to multiple potentially traumatic events. Although
      experiential avoidance was not associated with severity of posttraumatic stress
      symptoms beyond their shared relationship with general psychiatric symptom
      severity, it was associated with symptoms of depression, anxiety, and
      somatization when controlling for posttraumatic stress symptom severity. Thought
      suppression, on the other hand, was associated with severity of posttraumatic
      stress symptoms when controlling for their shared relationship with general
      psychiatric symptom severity. No significant relationships were found between
      thought suppression and the presence of depression, anxiety, and somatization
      symptoms when controlling for posttraumatic stress symptom severity. Results
      suggest the importance of separately examining the influence of different forms
      of experiential avoidance on posttraumatic psychopathology.

PMID- 15505520
TI  - Gender, social support, and posttraumatic stress in postwar Kosovo.
AB  - The effects of social support and traumatic experiences on mental health in
      conflict situations may be different by gender. The Kosovo Emergency Department
      Study was conducted in July and August 2001 to assess mental health 2 years after
      the end of the war in Kosovo. Of 306 emergency department patients (87.7%
      response rate), all were ethnic Albanian, 97.4% had experienced traumatic events,
      and 89.5% had posttraumatic stress symptoms. Women and persons who experienced
      more traumatic events had higher posttraumatic stress scores. Persons with social
      support had lower posttraumatic stress scores. In a final model, social support
      had a greater protective effect for women, whereas traumatic events had a greater
      detrimental effect on men. Two years after the war in Kosovo, there remained a
      high prevalence of posttraumatic stress symptoms, particularly among women with
      low social support. Interventions targeting social support may be important
      public health efforts in the postwar context.

PMID- 15505521
TI  - Is insight in mania state-dependent?: A meta-analysis.
AB  - In the first meta-analysis of studies assessing insight in mania, we sought to
      determine whether insight in mania is state-dependent or a trait-like condition.
      In schizophrenia, insight is a trait-like condition. If state-dependent, insight
      in mania would differ from insight in schizophrenia, and different treatment and
      research implications would follow. Seven reports using standardized insight
      rating scales in mania were identified through a MEDLINE literature search. Four
      longitudinal studies were included in a meta-analysis. The meta-analysis found
      that insight appears to be state-dependent. Insight showed a 20% improvement (95%
      confidence intervals, 7% to 34%) after recovery from acute mania (p = .003).
      Insight improves in bipolar disorder with resolution of the acute manic episode,
      suggesting that insight is state-dependent in bipolar disorder. We suggest that
      impaired insight be considered as part of the diagnostic picture of acute mania.

PMID- 15505522
TI  - Reexamining Tic persistence and Tic-associated impairment in Tourette's Disorder:
      findings from a naturalistic follow-up study.
AB  - The objective of this study was to assess tic persistence and tic-associated
      impairment in referred youth with Tourette's Disorder (TD). Subjects were 50
      youth (ages 6-17 years) who met DSM-IV diagnostic criteria for TD, were referred
      to a specialized TD program, and were evaluated by clinical and structured
      diagnostic interview. Tic severity and impairment was measured using the Yale
      Global Tic Severity Scale. The total tic score at or above minimal range defined
      tic persistence, and a TD impairment score at or above moderate range defined tic
      associated impairment. Results were assessed during administration of the Kiddie
      Schedule for Affective Disorders and Schizophrenia for School-Age Children
      Epidemiological Version. Mean age of onset of TD was 5.1 +/- 2.3 years, and mean
      illness duration was 5.6 +/- 3.2 years. At baseline, 88% of subjects met
      threshold criteria for at least mild tics, but only 30% met criteria for tic
      associated impairment. At 2-year follow-up, 82% of these subjects met criteria
      for tic persistence (NS change from baseline), but only 14% met criteria for TD
      associated impairment (p < .04 change from baseline). Although tics followed a
      persistent course in the majority of youth with TD, they were infrequently
      associated with impairment. There was a significant reduction in the proportion
      of youth with TD impairment from baseline to follow-up. These results support the
      view that TD is a persistent disorder, but suggest a dissociation between tic
      persistence and tic-associated dysfunction.

PMID- 15505523
TI  - Blink rate does matter: a study of blink rate, sustained attention, and
      neurological signs in schizophrenia.
AB  - This study aimed to explore the relationships among cognitive functions,
      neurological soft signs, and clinical symptoms in a group of patients with
      chronic schizophrenia. A total of 90 patients were recruited. Blink rate was
      recorded when patients were in a resting and relaxed condition. Significant
      correlations were found only between blink rate and general psychopathology (p <
      .01) and disinhibition soft signs (p < .05). When the group was further divided
      into two subgroups by taking the lower and upper quartiles of their blink rate,
      patients at the upper quartiles exhibited significantly more disinhibition signs
      than those at the lower quartiles. There was also a trend for those patients at
      the upper quartiles to commit more error in a sustained attention task. These
      findings suggest that blink rate is associated with disinhibition signs in the
      present sample.

PMID- 15505524
TI  - Social anxiety and agoraphobia in the eating disorders: associations with core
      beliefs.
AB  - The eating disorders have a high comorbidity with anxiety disorders, but it is
      not clear what cognitions underpin those anxiety symptoms. The present study
      investigated whether social anxiety and agoraphobia in eating-disordered
      individuals are associated with different types of unconditional core beliefs.
      The participants were 70 women meeting DSM-IV criteria for an eating disorder.
      The short version of Young's Schema Questionnaire (YSQ-S) was used as a measure
      of core beliefs, while the Social Phobia and Anxiety Inventory was used as a
      measure of levels of social anxiety and agoraphobia. Eating-disordered
      individuals reporting high levels of comorbid social anxiety had higher
      abandoment and emotional inhibition core beliefs. In contrast, patients with high
      levels of agoraphobia had higher vulnerability to harm beliefs. The findings
      highlight the importance of identifying and addressing core beliefs in subgroups
      of eating-disordered individuals presenting with comorbid anxiety. Implications
      for future research are discussed, including the need for longitudinal studies to
      elaborate on the specificity of the cognition-anxiety link in the eating
      disorders.

PMID- 15505525
TI  - Effects of brief cognitive-behavioral interventions on confidence to resist the
      urges to use heroin and methamphetamine in relapse-related situations.
AB  - The aim of this study was to examine the effect of brief cognitive-behavioral (C
      B) intervention on improving confidence in managing situations related to heroin
      and methamphetamine (MAMP) use in drug users. The subjects in the intervention
      group received a five-session C-B intervention, which focused on the acquisition
      of skills aimed at helping the subject to reduce drug use. The subjects in the
      intervention and control groups completed pretest and posttest assessments to
      determine the changes of confidence in managing situations related to drug use. A
      total of 70 subjects (40 heroin and 30 MAMP users) and 75 subjects (38 heroin and
      37 MAMP users) in the control group completed pretest and posttest assessments.
      The results revealed that among heroin users, the intervention group had greater
      improvement in confidence to manage interpersonal situations related to heroin
      use than did the control group, but there was no difference in the improvement in
      confidence to manage intrapersonal situations between the two groups.
      Furthermore, MAMP users in the intervention group showed greater improvement in
      confidence to manage both intrapersonal and interpersonal situations related to
      MAMP use than the control group. The present study confirmed the efficacy of
      brief C-B interventions in improving confidence in ability to resist urges to use
      heroin and MAMP in stressful interpersonal situations and to use MAMP in
      intrapersonal situations. The possible explanations for the ineffectiveness of
      brief C-B interventions to improve confidence in managing intrapersonal
      situations related to heroin use are discussed.

PMID- 15505526
TI  - Quality of life in unipolar and bipolar depression: are there significant
      differences?
AB  - In the present investigation, we compared the impact of illness on quality of
      life (QOL) in adult outpatients with unipolar (N = 89) and bipolar (N = 25)
      depression. While attending a university hospital in southern Brazil, patients
      completed the WHO's QOL Instrument-Short Version and the Beck Depression
      Inventory. After analyses, patients with bipolar depression reported
      significantly lower scores on the psychological QOL domain (p = .013) than
      patients with unipolar depression. There were no significant differences between
      the study groups in terms of social and demographic variables, in the other QOL
      domains assessed (i.e., physical health, social relationships, and
      environmental), and in the severity of depressive symptoms. In conclusion, our
      findings suggest that patients with bipolar and unipolar depressions have
      different QOL profiles, and that this difference is probably independent of the
      severity of the mood disturbance and might be related to the higher rates of
      suicide observed in the bipolar population.

PMID- 15505527
TI  - Bipolar disorder in middle-aged and elderly adults: is age of onset important?
AB  - The literature is mixed about whether age of onset is a useful variable in
      explaining the heterogeneity of late-life bipolar disorder. The aim of this study
      was to examine the relationship of age of onset with clinical, family history,
      and neuropsychological functioning in middle-aged and older patients with bipolar
      disorder. A total of 87 outpatients with bipolar disorder with a mean age of 59
      (range, 42-89) were included in this study. Age of onset was analyzed as a
      continuous variable and was split at age 40 years into early-onset and late-onset
      groups. Participants were administered measures of psychopathology, cognitive
      functioning, and medication usage. Few meaningful differences emerged between
      early-onset and late-onset groups, except that overall psychopathology was
      significantly lower in the late-onset group. Age of onset did not relate to
      differences in family history, depressive symptoms, cognitive functioning, or
      medication use whether used as a categorical or continuous variable. Thus, the
      validity of late-onset bipolar disorder as a distinct syndrome was not
      corroborated by this study. Interpretation of these findings is limited by the
      sample size, cross-sectional design, and a lack of brain imaging data. Further
      research on the clinical features and neurobiological aspects of late-life
      bipolar disorder is needed.

PMID- 15505528
TI  - Follicular neoplasms of the thyroid: view, biases, and experiences.
AB  - The authors review the group of thyroid tumors characterized by a follicular
      growth pattern; these include follicular adenoma, follicular carcinoma, and the
      follicular variant of papillary carcinoma. Most of these lesions can be diagnosed
      with ease, but a subgroup has generated recent controversy in the literature. The
      authors present their views based on their experience with the cytologic and
      histologic diagnosis of these tumors and propose a scheme to assist in their
      classification and appropriate clinical management.

PMID- 15505529
TI  - Ovarian neoplasms composed of small round cells: a review.
AB  - Ovarian neoplasms composed predominantly or exclusively of small round cells with
      scant cytoplasm are relatively rare. However, there is a wide differential, and
      pathologists often struggle to make a correct diagnosis because of overlapping
      histologic features. Perhaps the best known of these neoplasms is ovarian small
      cell carcinoma of hypercalcemic type (OSCCHT), a tumor of unknown histogenesis.
      This may be confused with a wide range of neoplasms ranging from sex cord-stromal
      tumors (some of which may exhibit a small cell phenotype) to neoplasms in the
      family of small round blue cell tumors to various undifferentiated malignancies.
      A neuroendocrine small cell carcinoma, so-called small cell carcinoma of
      pulmonary type, may also arise within the ovary, and this may be a component of a
      typical ovarian surface epithelial-stromal tumor. In addition to the well-known
      family of small round blue cell tumors of childhood, other small cell neoplasms
      that may arise within the ovary or involve the ovary include intra-abdominal
      desmoplastic small round cell tumor, metastatic small cell carcinoma, peripheral
      and central primitive neuroectodermal tumor, and endometrial stromal sarcoma.
      Malignant melanoma, undifferentiated carcinoma, and various germ cell tumors,
      especially dysgerminoma and immature teratoma, also on occasion enter into the
      differential diagnosis of an ovarian small cell neoplasm. In this review, the
      morphologic features of some of these neoplasms are described, as is the value of
      immunohistochemistry and other ancillary techniques in establishing a diagnosis.

PMID- 15505530
TI  - Carcinomas with micropapillary morphology: clinical significance and current
      concepts.
AB  - Invasive micropapillary carcinoma has been recently recognized as a rare but
      distinctive variant of carcinoma in various anatomic sites, including breast,
      urinary bladder, lung, and major salivary glands. Morphologically, it is
      characterized by small tight clusters of neoplastic cells floating in clear
      spaces resembling lymphatic channels. Most often this growth pattern is mixed
      with a variable component of conventional carcinoma or other variants. In
      addition to a unique morphology, tumors with invasive micropapillary growth share
      a high propensity for lymphovascular invasion and lymph node metastases. Patients
      have typically high-stage disease at presentation and a poor clinical outcome
      compared with that of patients with conventional carcinoma arising in the same
      organ site. In this article the author reviews the available literature on tumors
      displaying a micropapillary component.

PMID- 15505531
TI  - Molecular basis of proteinuria.
AB  - The glomerular filtration barrier is composed of endothelial cells, basement
      membrane, and podocytes. In recent years, remarkable progress has been made in
      our understanding of the molecular structure of the filtration barrier and its
      relation to the effectiveness of the barrier function. The glomerular basement
      membrane is composed of a multitude of proteins, including collagen IV, heparan
      sulfate proteoglycans, and laminin, among others. The slit diaphragm, which is
      seen as a membrane covering the space between adjacent foot processes close to
      the basement membrane, is an extremely important structure with a crucial role in
      permselectivity of the filtration barrier. Its composition is now understood to
      consist primarily of a unique protein called nephrin. Mutations in the gene
      encoding nephrin are known to result in the Finnish type of nephrotic syndrome.
      The exact mechanism by which nephrin controls permselectivity is not yet clear,
      but it is known to interact with several podocyte proteins including CD2AP,
      podocin, and alpha-actinin-4. Abnormalities of any of these proteins may result
      in proteinuria. The role of nephrin and its associated proteins in the
      pathogenesis of common acquired glomerulopathies in humans is still under
      investigation. Normal function of podocyte also depends upon maintaining a fully
      mature and terminally differentiated phenotype. A host of transcription factors,
      especially WT1 and PAX2, play a significant role in modulating podocyte function.

PMID- 15505532
TI  - CD10 expression in the female genital tract: does it have useful diagnostic
      applications?
AB  - In the female genital tract, CD10 was initially found to be expressed in
      endometrial stromal tumors of the uterus as well as in mesonephric remnants and
      related lesions and was thought to be helpful in distinguishing these tumors from
      their mimics. However, new studies have shown CD10 to be expressed in a wide
      range of tumors of the female genital tract, making this antibody of limited
      diagnostic value. This review discusses diagnostic applications of CD10 in the
      female genital tract, with emphasis on CD10 use in mesenchymal tumors of the
      uterus and in the differential diagnosis of mesonephric versus non-mesonephric
      carcinomas, where CD10 positivity alone may be misleading in the final
      classification of a tumor. CD10 may be useful in establishing the diagnosis of
      endometriosis (with the exception of the cervix), distinguishing metastatic renal
      clear cell carcinoma from a primary ovarian clear cell carcinoma, and
      distinguishing mesonephric hyperplasia from other benign glandular proliferations
      of the cervix.

PMID- 15505533
TI  - Diagnostic utility of alpha-methylacyl CoA racemase (P504S) on prostate needle
      biopsy.
AB  - Alpha-methylacyl CoA racemase (AMACR), also known as P504S, was identified by the
      analysis of cDNA library subtraction in conjunction with high throughput
      microarray screening from prostate tissue and has been proven to be one of the
      very few biomarkers that can distinguish cancer from benign cells with high
      sensitivity and specificity for prostate carcinoma. It is a successful example of
      the translation of molecular findings into clinical practice. This review focuses
      on the study of AMACR (P504S) expression in small focal prostate cancer and
      atypical small acinar proliferation (ASAP) on needle biopsies and emphasizes the
      utility of AMACR (P504S) in routine surgical pathology practice. We also discuss
      the potential pitfalls and caveats in the interpretation of immunostaining
      results.

PMID- 15505534
TI  - Borderline ovarian tumors: a web-based atlas.

PMID- 15505540
TI  - [Off label prescriptions: from creativity to rigour].

PMID- 15505541
TI  - [What are the stakes for a perennial drug?].

PMID- 15505542
TI  - [Granuloma with lymphocytic hyperplasia following vaccination: 10 cases. Presence
      of aluminium in the biopsies].
AB  - BACKGROUND: Few cases of cutaneous lymphocytic hyperplasia secondary to
      vaccination have been published, although such lesions are not rare. PATIENTS AND
      METHODS: We report a series of 10 cases registered between 1993 and 2003.
      RESULTS: Mean age was 25. The clinical aspect was solitary or multiple
      subcutaneous nodules, located on the arm, developing after a delay of 1 to 18
      months after vaccination. Histologic examination showed a lymphocytic
      infiltration of the subcutaneous fat, with diffuse and/or follicular pattern,
      without nuclear atypia, the morphological and immunohistochemical analysis of
      which revealed the benign nature. In all cases, there was fibrosis and granuloma
      composed of lymphocytes, plasma cells, eosinophils and macrophages with
      basophilic cytoplasm. Morin stain showed intralesional aluminium in the 6
      investigated cases. Evolution was always benign, with no relapse following
      exeresis. DISCUSSION: Cutaneous lymphocytic hyperplasia secondary to vaccination
      has to be suspected in a young patient with subcutaneous nodules appearing at a
      vaccination site. Evidence of aluminium in the lesions supports the diagnosis and
      the hypothesis that aluminium in the vaccine excipient might have a role in the
      onset of such lesions.

PMID- 15505543
TI  - [Lymphedema of the limb: predictors of efficacy of combined physical therapy].
AB  - BACKGROUND: Limb lymphedema results from incompetence of the lymphatic system,
      and treatment of both primary and secondary forms involves manual lymphatic
      drainage and support. The effectiveness of treatment varies from patient to
      patient and can be unpredictable. OBJECTIVE: To investigate clinical and
      paraclinical criteria able to predict responses to combined physical treatment
      (lymphatic drainage and multilayered support) during hospitalization. PATIENTS
      AND METHODS: A retrospective study was performed in 45 patients admitted for one
      week's intensive treatment of limb lymphedema in the Lymphology Unit of the
      Department of Dermatology of the University Hospital of Tours. Lymphoscintigraphy
      was performed for all patients on admission. Loss of volume in affected limbs was
      studied to evaluate the effectiveness of treatment. RESULTS: Two criteria were
      predictive of resistance to combined treatment, i.e. venous insufficiency and
      continuing lymph node evidence of scintigraphic activity four hours after
      lymphoscintigraphy. The two factors were significantly related. CONCLUSION:
      Failure of combined physical treatment for lymphedema appears to be related to
      venous insufficiency. It is therefore essential to investigate and treat venous
      insufficiency, particularly in patients with continuing evidence of scintigraphic
      activity in lymph nodes.

PMID- 15505544
TI  - [Knowledge and problems regarding the topical treatment of leg ulcers: survey
      among general practitioners in the Indre-et-Loire area].
AB  - INTRODUCTION: The quantity of topical treatments for leg ulcers has increased
      over the last 15 years. OBJECTIVE: To determine the prescriptions for topical
      treatments and the problems in the management of leg ulcers using a questionnaire
      sent to general practitioners. MATERIAL AND METHODS: A questionnaire in 3 parts
      was sent to 95 general practitioners in the area working in 36 different
      districts with an explanatory letter. The first part was composed of 29 closed
      questions regarding prescription of topical treatment for leg ulcers. The second
      part, also closed, included 3 pictures showing a budding, a necrotic and a
      fibrinous ulcer. The physicians had to choose which treatment they would have
      prescribed and the frequency of dressings changes. The third part was composed of
      two open questions regarding the problems encountered. The survey started on May
      1st and was closed on June 30th 2002. No reminders were sent. RESULTS: We
      received 52 replies, 49 of which were exploitable. Forty-five percent (43/95) did
      not reply. Occlusive dressings were widely prescribed (mainly hydrocolloid 38/49
      and hydrocellular 28/49). Vaseline impregnated gauze were less prescribed
      (14/49). Dressings with balsam of Peru were prescribed often by 10 and
      occasionally by 27 general practitioners. Alginate or charcoal dressings were not
      always used appropriately. Antiseptics were prescribed by 10 physicians.
      Mechanical debridement of fibrinous or necrotic wounds was rarely used even for
      necrotic ulcers. Topical anesthetics were prescribed in 21 out of 33 cases of
      mechanical debridement. Some physicians referred care (n=4), others complained
      about lack of compliance (n=15), cost (n=14), local intolerance (n=10) and the
      excessively wide variety of dressings (n=10). We drew-up a synopsis with
      guidelines for treatment, which was sent to all the general practitioners who had
      participated in the survey. CONCLUSION: Forty-three of the 95 physicians
      approached did not reply. This poor response rate, which is common in this type
      of survey, may include physicians who are not at ease in the management of ulcers
      and this may bias the results. The physicians who replied to the survey knew the
      subject well but complained of the costs and variety of dressings. They were all
      eager to receive further information and guidelines.

PMID- 15505545
TI  - [Tabetic arthropathy: "a forgotten disease"].
AB  - INTRODUCTION: With the current sparcity of syphilitic manifestations, the once
      obvious aspects of the affection have been forgotten or are little known. We
      report 4 cases of tabetic arthropathy admitted to the Dermatology Department Ibn
      Rochd University Hospital of Casablanca. OBSERVATIONS: The mean age of the
      patients was 50 years, all were males. The diagnosis was based on clinical,
      radiological, and biological criteria. There was a large contrast between the
      extent of the articular malformation and the indolence. The radiological aspect
      associated destructive and constructive lesions. The syphilis serology was
      positive in the articular liquid, the blood and/or the cerebro-spinal fluid.
      Treatment was essentially medical. DISCUSSION: Tabetic arthropathy, an
      exceptional affection, is one of the complications of the tabes dorsalis. Its
      prevention relies on the treatment of the syphilis at an early stage, before the
      onset of the articular and neurologic forms, the management of which remains very
      difficult.

PMID- 15505546
TI  - [Giant cutaneous squamous cell carcinoma of the nose with subsequent brain
      extension].
AB  - INTRODUCTION: Cutaneous squamous cell carcinoma is an invasive and destructive
      tumor, and may cause death by local extension or because of metastasis. We report
      the case of a patient with a giant squamous cell carcinoma of the nose and
      extension to the brain and discuss the main risk factors from this extension.
      OBSERVATION: Resection of a giant squamous cell carcinoma was performed of the
      nose in a 45 year-old man after debulking radiotherapy. Histological examination
      disclosed a well-differentiated tumor and perineural involvement, with at least a
      6 mm margin. A first relapse occurred on the orbital edge of the initial
      resection, the lesion was removed revealing an involvement of the infra-orbital
      nerve. Whilst the patient was receiving chemotherapy, a second relapse occurred
      responsible for ophthalmoplegia and loss of vision, with involvement of the left
      orbital apex, cavernous sinus and temporal lobe. The patient died from grand mal
      seizures. DISCUSSION: Brain extension of cutaneous squamous cell carcinoma of the
      head is rare. It develops along the anatomic pathways, especially perineural
      spread. Main risk factors for such a poor course are discussed, including the
      size of tumor, the anatomic site, the depth and perineural invasion.

PMID- 15505547
TI  - [Superficial granulomatous pyoderma].
AB  - INTRODUCTION: Superficial granulomatous pyoderma is a rare variant of pyoderma
      gangrenosum, which is often diagnosed at a late stage because of misleading
      clinical-histopathological features. We report a new case of this rare disease.
      CASE REPORT: A 67 year-old man presented with inflammatory lesions that had
      become ulcerated over the past 4 months despite prolonged antibiotic therapy. The
      histopathological aspect was initially suggestive of palisading granuloma
      annulare and subsequently a necrotizing granuloma compatible with a
      mycobacteriosis. The various supplementary examinations eliminated the
      possibility of an infectious or systemic disease. The lesions became painful and
      ulcerated. A second biopsy showed a neutrophilic dermatosis with dermal necrosis
      and a granuloma leading to the diagnosis of superficial granulomatous pyoderma.
      The lesions healed after 3 months of systemic corticosteroids at the dose of 1
      mg/kg/day. DISCUSSION: The clinical features of superficial granulomatous
      pyoderma are similar to those of classical pyoderma gangrenosum. However, its
      histological profile is more superficial and is associated with dermal
      granulomas. The latter are unusual in neutrophilic dermatosis and would suggest
      an infectious disease. This explains the frequent diagnostic errors, with
      inappropriate anti-infectious treatments and notably unnecessary surgical
      exeresis.

PMID- 15505548
TI  - [Iatrogenic acrodermatitis enteropathica-like syndrome in leucinosis].
AB  - INTRODUCTION: Leucinosis (maple syrup urine disease) is a metabolic disorder
      caused by an enzymatic deficiency involved in the degradative pathways of the
      three branched-chain amino acids. We report an observation of acrodermatitis
      enteropathica-like syndrome induced by essential amino acid deficiency in a child
      with leucinosis. CASE REPORT: A child with leucinosis was referred to our
      hospital for exfoliative dermatitis of the perioral and anogenital regions
      associated with diarrhea and pancytopenia. The diagnosis of iatrogenic
      acrodermatitis enteropathica-like syndrome was confirmed after screening showing
      isoleucine deficiency. Rapid response was observed after adequate isoleucine
      supplementation. DISCUSSION: The acrodermatitis enteropathica-like eruption in
      our patient was due to an iatrogenic amino acid nutritional imbalance. Our
      observation underlines the risk of using a branched-chain amino acid-free formula
      without adequate supplementation of deficient amino acids. In addition, dietary
      insufficiency of isoleucine, associated with the treatment of organic aciduria
      should be added to the causes of acrodermatitis enteropathica-like syndrome.

PMID- 15505549
TI  - [Linear Darier disease in two siblings. An example of loss of heterozygosity].
AB  - BACKGROUND: Darier's disease or keratosis follicularis is an autosomal dominant
      acantholytic disorder that frequently arises as a result of spontaneous mutation.
      It is either a generalized or localized condition due to a mutation in the SERCA2
      12q23-q24,1 resulting in a faulty organization of the tonofilaments. We present
      two siblings affected with the linear form of this disorder and discuss these
      cases as an example of the genetic mechanism of loss of heterozygosity. CASE
      REPORTS: A 7 year-old girl was referred for evaluation of linear lesions present
      since the first year of age. Examination disclosed red, 1 to 2 mm papules that
      coalesced to form linear plaques on the left side of the vulvar and perianal
      areas, and on the left hand and foot. Her older brother had similar lesions in a
      linear arrangement on the left side of the face neck and homolateral foot. No
      lesions were found in their parents. Biopsies of both affected children revealed
      an intraepidermal suprabasal cleft. Dyskeratotic cells were present in the
      spinous layer, and corps ronds and grains near the granular layer. DISCUSSION:
      The linear form of Darier's disease could result from genetic mosaicism for this
      autosomal dominant disorder. As these children have a more pronounced involvement
      than the usual Darier's disease lesions, disposed in a linear arrangement, they
      probably represent a type 2 segmental manifestation of the disorder. Likewise,
      the presence of the same linear disorder in two siblings could be explained by
      loss of heterozygosity for the Darier's disease gene.

PMID- 15505550
TI  - [Familial dyskeratotic comedone].
AB  - INTRODUCTION: Familial dyskeratotic comedones is a rare affection of autosomal
      transmission and characterized by pseudo-comedone papules predominantly on the
      limbs. We report a new familial case characterized by its clinical and
      histological profile. CASE REPORT: A 6 year-old boy presented with a papular,
      pseudo-comedone eruption that had appeared shortly after birth and had
      progressively extended symmetrically to both legs. The child's father complained
      of a similar eruption since childhood. Histological examination of the papules
      revealed a pseudo-follicular invagination, obstructed by keratin and associated
      with areas of focal dyskeratosis. Treatment with local retinoids was ineffective.
      DISCUSSION: Since it is often asymptomatic, the prevalence of dyskeratosis
      comedones is probably underestimated. A review of the literature on the preceding
      observations is presented. The dermatites that would represent differential
      diagnoses because of the presence of comedone-like lesions and/or histological
      dyskeratosis are discussed.

PMID- 15505551
TI  - [Inguinal pseudotumor: relapse of a pemphigus after 15 years' remission].
AB  - INTRODUCTION: Pemphigus vegetans (PV) is a rare type of pemphigus vulgaris. We
      report a patient with pemphigus vulgaris relapsing as an isolated vegetative
      tumour. CASE REPORT: A 59-year-old man was seen in February 2001 for a tumour on
      the right groin. He had received systemic corticosteroids and cyclophosphamide
      for pemphigus vulgaris from 1974 to 1985, and he had been in complete remission
      since 1985. At the time of evaluation, a 10 x 5 x 5 cm, smooth vegetative tumour
      was seen on the right groin. Biopsies showed spongiosis, acanthosis and some
      acantholysis. Direct immunofluorescence showed strong deposition of
      immunoglobulin G within the intercellular substance of the epidermis. Indirect
      immunofluorescence revealed anti-intercellular antibodies at a titer of 1/800.
      Immunoblot analysis showed reactivity with the 130 kD pemphigus vulgaris antigen.
      PVg was diagnosed. Local corticosteroid treatment was initiated. The patient was
      disease-free at follow-up three years later. DISCUSSION: Localised forms of
      pemphigus are very rare. Twenty four other cases have been reported among them
      just one case of localised PV. Our case report is very unusual because of the
      variability of the expression of the disease, the high antibody level, the
      absence of trigger factors, and the efficacy of the local corticosteroid
      treatment.

PMID- 15505552
TI  - [Cutaneous epithelioid hemangioendothelioma].
AB  - INTRODUCTION: Epithelioid hemangioendothelioma is a tumor of soft tissues arising
      from the vascular endothelium. It is considered as a low-grade malignant tumor.
      Cutaneous involvement is rare and often associated with multi-systemic
      localizations. CASE REPORT: We report the case of a 34 year-old woman with a 6
      month history of a 1.5 cm erythematous-violaceous, soft, painful cutaneous nodule
      involving the right forearm. An abdominal sonography had been performed 1 month
      before the onset of the nodule, because of epigastric pain and was normal.
      Histological and immunohistological examinations led to diagnosis of an
      epithelioid hemangioendothelioma. Assessment of the extension with radiology,
      sonography, tomodensitometry and magnetic resonance imaging, revealed nodules of
      the liver. Treatment consisted in the wide and complete excision of the tumor.
      There was no evidence of local recurrence after one year follow-up, and the
      hepatic lesions were stable. DISCUSSION: Epithelioid hemangioendotheliomas belong
      to the epithelioid vascular tumor spectrum. They have in common the morphologic
      epithelioid aspect of endothelial tumor cells. Cutaneous localization is rare,
      and to the best of our knowledge, only 20 cases of epithelioid
      hemangioendothelioma with skin involvement have been reported in the literature.
      Epithelioid hemangioendothelioma can be isolated or associated with internal
      visceral involvement. The detection of skin lesions should lead to a complete
      assessment of the extension of the disease to detect any internal localization.
      Because of low-grade malignancy of the tumor, and the integrity of the liver
      observed one month before the onset of the disease in our patient, epithelioid
      hemangioendothelioma appears to be a multicentric disease rather than metastatic
      hepatic localizations of a primitive skin cancer.

PMID- 15505553
TI  - [Palmoplantar lichen nitidus: a rare cause of palmoplantar hyperkeratosis].
AB  - BACKGROUND: Lichen nitidus is a rare condition, which may be a cause of
      palmoplantar hyperkeratosis. We report two cases. CASE REPORTS: A 53 year-old
      woman presented with a dry and fissured palmoplantar hyperkeratosis. Histological
      examination of a biopsy showed the typical features of lichen nitidus.
      Significant improvement was obtained with acitretin. A few months later, multiple
      lichen nitidus papules appeared on the limbs and the abdomen. A 67 year-old woman
      was referred to us for a fissured, disabling palmoplantar hyperkeratosis
      refractory to topical steroids. Histological examination led to the diagnosis of
      lichen nitidus. Local PUVA therapy resulted in the cleaning of her lesions.
      Later, typical papules of lichen nitidus appeared on her elbows. DISCUSSION:
      Nineteen cases of palmoplantar localization of lichen nitidus have been
      described. The features are usually tiny yellow papules but sometimes a non
      specific keratoderma resembling chronic eczema. Palmoplantar involvement of
      lichen nitidus may be isolated or associated with cutaneous lesions on unusual
      sites. Oral retinoids and local PUVA are effective treatments.

PMID- 15505554
TI  - [Porphyria: from clinics to molecular genetics].

PMID- 15505555
TI  - [Hospitalisation modes for patients with acute dermatoses].

PMID- 15505556
TI  - [Acute generalized exanthematous pustulosis induced by iopamidol].

PMID- 15505558
TI  - [Ulcerated inflammatory plaque on the leg].

PMID- 15505557
TI  - [Hemorrhagic erysipelas of the lower limbs: 5 cases].

PMID- 15505559
TI  - [NK phenotype and/or cytotoxic-cell cutaneous lymphomas].

PMID- 15505560
TI  - [Pediculosis].

PMID- 15505562
TI  - [Mycosis fungoides].

PMID- 15505561
TI  - [Allergy to mercaptobenzothiazole and mercapto mix].

PMID- 15505563
TI  - [Mutations in the cyto skeletal-extra cellular matrix connector genes in Weary
      Kindler's poikiloderma].

PMID- 15505564
TI  - [Actinomyces meyer primitive actinomycosis around the nails].

PMID- 15505565
TI  - [Laser and hidradenitis suppurativa?].

PMID- 15505566
TI  - [Rofecoxib and gynecomastia: the first case].

PMID- 15505569
TI  - Lung cancer. A deadly and potentially preventable disease.

PMID- 15505567
TI  - [Deep changes].

PMID- 15505572
TI  - Symptoms not to ignore. What should you do about them?

PMID- 15505573
TI  - Getting your flu shot. Setting the facts straight about the flu vaccine.

PMID- 15505574
TI  - Memories are made of this. Understanding how your mind works.

PMID- 15505575
TI  - One on one. I've heard white tea may have more health benefits than green tea
      has. Is that true?

PMID- 15505576
TI  - One on one. I've had a mastectomy. Is it OK if I use the arm on the side of the
      surgery to get my blood pressure taken and blood drawn?

PMID- 15505577
TI  - One on one. Is it OK for me to split my prescription drug tablets to save money?

PMID- 15505580
TI  - Aspirin. A look at an old drug's new uses.

PMID- 15505586
TI  - Sepsis. When an infection becomes life-threatening.

PMID- 15505584
TI  - Report on cancer. Rates of incidence and mortality decrease for many cancers.

PMID- 15505587
TI  - Working off what you eat. How much exercise do you need to burn extra calories?

PMID- 15505589
TI  - One on one. I've had a total hysterectomy. Do I still need to have a Pap test?

PMID- 15505588
TI  - One on one. I'm allergic to my cat, but I don't want to get rid of her. Is there
      anything I can do to keep her dander to a minimum?

PMID- 15505590
TI  - One on one. What does it mean when a test result is called false-negative or
      false-positive?

PMID- 15505592
TI  - The importance of redox state in liver damage.
AB  - Oxidative stress is a major pathogenetic event occurring in several liver
      disorders ranging from metabolic to proliferative ones, and is a major cause of
      liver damage due to Ischemia/Reperfusion (I/R) during liver transplantation. The
      main sources of ROS are represented by mitochondria and cytocrome P450 enzymes in
      the hepatocyte, by Kupffer cells and by neutrophils. Cells are provided with
      efficient molecular strategies to strictly control the intracellular ROS level
      and to maintain the balance between oxidant and antioxidant molecules. A cellular
      oxidative stress condition is determined by an imbalance between the generation
      of ROS and the antioxidant defense capacity of the cell and can affect major
      cellular components including lipids, proteins and DNA. Proteins are very
      important signposts of cellular redox status and through their structure/function
      modulation, ROS can also influence gene expression profile by affecting
      intracellular signal transduction pathways. While several enzymatic (such as
      superoxide dismutase, catalase, glutathione peroxidase) and non enzymatic (such
      as 4-hydroxynonenal, decrease of glutathione, vitamin E, vitamin C,
      malondialdehyde) markers of chronic oxidative stress in liver are well known,
      early protein targets of oxidative injury are yet not well defined.
      Identification of these markers will enable early detection of liver diseases and
      will allow monitoring the degree of liver damage, the response to pharmacological
      therapies and the development of new therapeutic approaches. In the new era of
      molecular medicine, new proteomics methodologies promise to establish a
      relationship between pathological hallmarks of disease and protein structural and
      functional abnormalities in liver disease, thus allowing a better understanding
      and a more rational therapy on these disorders.

PMID- 15505593
TI  - Nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease is a clinicopathologic syndrome that encompasses
      several clinical entities. The spectrum of conditions ranges from simple
      steatosis to steatohepatitis, fibrosis and end stage liver disease. The condition
      was originally described in obese, diabetic, middle-aged females without a
      history of significant alcohol use with liver histology consistent with alcoholic
      hepatitis. It is known that this entity occurs without any particular sex
      predilection, in lean individuals, as well as an increasing number of obese
      children. Other terms have been used to describe this clinical entity such as
      alcohol-like hepatitis, pseudo-alcoholic hepatitis, diabetic hepatitis and
      steatonecrosis. Ludwig and colleagues introduced the term nonalcoholic
      steatohepatitis (NASH) to describe patients fitting the picture of alcoholic
      hepatitis but without a history of significant alcohol abuse. The term
      nonalcoholic fatty liver disease (NAFLD) is used more frequently to include the
      spectrum of conditions that range from steatosis through steatohepatitis,
      fibrosis and cirrhosis. NASH is reserved for patients with steatohepatitis and
      fibrosis. NAFLD is now being recognized as the most common cause of elevated
      liver enzymes in the United States. Although the exact etiology of NAFLD is not
      known, it may be caused by insulin resistance coupled with increased oxidative
      stress to the hepatocytes. No specific therapy has been approved for this
      condition and the mainstay of management is weight loss.

PMID- 15505594
TI  - Transjugular liver biopsy. An update.
AB  - Transjugular liver biopsy was first reported in 1967. Since then, this technique
      has been broadly performed in many medical centers around the world. The number
      of its indications has increased, and by modifying the needles, the quality of
      the liver tissue sample has improved. The advantage of transjugular biopsy is
      that it can be performed in patients in whom the use of percutaneous biopsy is
      contraindicated Indications for transjugular liver biopsy are, precisely, most of
      the contraindications for percutaneous liver biopsy. This fact increases the
      number of patients that can benefit from this procedure. In most cases, the
      procedure is successfully performed. Minor complications may occur in 1% to 15%
      and major complications (perforation of the hepatic capsule, cholangitis, and
      intra-peritoneal bleeding) are observed in 1-3% of the cases. Mortality related
      to the procedure varies form 0.2 to 0.3%. It has been reported that diagnosis
      yielded by transjugular liver biopsy induced changes of treatment in 50% of
      patients with an acute hepatic illness, in 62% of the patients with a chronic
      hepatic illness, and in 87% of the patients with liver transplants. In
      conclusion, transjugular liver biopsy is a useful procedure in the diagnosis of
      hepatic diseases. Its success rate is high; it is a very safe procedure because
      complications and mortality are rare; and it is well tolerated by patients.

PMID- 15505595
TI  - Effects of ribavirin on cytokine production of recall antigens and
      phytohemaglutinin-stimulated peripheral blood mononuclear cells. (Inhibitory
      effects of ribavirin on cytokine production).
AB  - AIM: To evaluate the effects of ribavirin on cytokine production of recall
      antigen and PHA-stimulated PBMC obtained from healthy individuals. MATERIALS AND
      METHODS: PBMC were challenged with tetanus toxoid (5 microg/mL) and PHA (10
      microg/mL) in absence or presence of ribavirin at different concentrations (1, 10
      and 100 (microM). Parallel sets of wells containing PBMC exposed to medium alone
      were used as negative controls. On day 3 after initiation of the cultures, IL-2,
      IFN-gamma, IL-4, IL-10, TNF-alpha content were determined in supernatants of PBMC
      from the different individuals. RESULTS: The effects of ribavirin on cytokine
      released by human PBMC in response to PHA and TT showed a great variation among
      individuals. No significant changes were observed between 1-10 microM
      concentrations in the production of TNF-alpha, IFN-gamma and IL-10 by both PHA
      and TT-stimulated PBMC. Ribavirin inhibited TNF-alpha, IFN-gamma, and IL-10 in
      both PHA and TT-stimulated PBMC at 100 microM (p <0.05). At this concentration,
      ribavirin induced an increase of 124% in the production of IL-2 by PHA-stimulated
      PBMC (p <0.05). CONCLUSIONS: The present data suggest that ribavirin may cause
      diverse effects on immunoregulatory cytokine secretion with changes in the
      Th1/Th2 balance.

PMID- 15505596
TI  - Weight reduction and ursodeoxycholic acid in subjects with nonalcoholic fatty
      liver disease. A double-blind, placebo-controlled trial.
AB  - OBJECTIVE: Nonalcoholic fatty liver disease is an increasingly recognized
      condition that may progress to end-stage liver disease. We investigated the
      effects of weight reduction and ursodeoxycholic acid administration in patients
      with this disease. RESEARCH METHODS AND PROCEDURES: A double-blind, placebo
      controlled trial. Twenty-seven women with a body mass index of >30 kg/m2 and
      willing to participate in the diet plan for six weeks were studied were assigned
      to one of two treatment groups (ursodeoxycholic acid, n = 14: placebo n = 13).
      Both groups received a normal diet (1,200 kcal/d) plus 1200 mg/d of
      ursodeoxycholic acid or placebo. Hepatic steatosis, was assessed by abdominal
      ultrasound. Fasting glucose, cholesterol, triglycerides, and aminotransferases
      levels were determined before and after treatment. RESULTS: Body mass index
      decreases significantly from 34.2 +/- 4.2 kg/m2 and 33.3 +/- 1.6 kg/m2 to 31.8 +/
      4.5 kg/m2 and 30.6 +/- 2.6 kg/m2 in the ursodeoxycholic acid and placebo groups,
      p < 0.001. The hepatic steatosis index decreased from 2.3 +/- 0.7 to 1.0 +/- 0.6
      and 2.2 +/- 0.7 to 1.1 +/- 0.7 in the ursodeoxycholic acid and placebo groups,
      p<0.003. Serum AST decreased significantly from 41.2 +/- 5.6 to 34.5 +/- 3.4 in
      the ursodeoxycholic acid group, p <0.001, and from 43.6 +/- 4.2 to 35.3 +/- 2.9
      in the placebo group, p <0.001. Serum ALT decreased from 62.9 +/- 6.5 to 44.0 +/-
      3.5 in the ursodeoxycholic acid group, p <0.001, and from 63.5 +/- 4.5 to 44.0 +/
      3.5 in the placebo group. We did not find any differences in all variables
      studied between groups. CONCLUSIONS: The present study shows beneficial effect of
      weight reduction, producing improvements in biochemical and imaging markers of
      liver disease.

PMID- 15505597
TI  - Effect of S-Nitrosoglutathione (GSNO) added to the University of Wisconsin
      Solution (UW): mast cell degranulation during normothermic reperfusion.

PMID- 15505598
TI  - Polysplenia syndrome in the adult patient. Case report with review of the
      literature.
AB  - AIMS: To report a case of polysplenia syndrome (PSS) in an adult patient.
      BACKGROUND: The PSS is a form of situs ambiguous with multiple spleen, cardiac
      anomalies, abdominal heterotaxia, short pancreas, major venous system and
      bronquial malformations. It is a rare syndrome, more often found in childhood,
      and only the 10% of the patients that do not have cardiac anomalies can reach
      adulthood. RESULTS: A 56 y/o male with obstructive jaundice and intestinal
      obstruction who was submitted to an abdominal laparotomy suspecting
      cholangiocarcinoma. He had choledocolithiasis, duodenal kinking by a preduodenal
      portal vein, intestinal levorotation, hypoplasic vena cava with a prominent
      acigos vein, short pancreas and polysplenia. A cholecistectomy, biliodigestive
      and gastroyeyunal bypasses were performed without any complications and with a
      successful evolution. CONCLUSIONS: In conclusion, PSS is a rare hereditary
      syndrome that often occurs in childhood and its discovery in an adult is
      frequently fortuitus. Surgical treatment is an excellent therapeutic option,
      however is reserved just for complications. The outcome is good and the final
      evolution depends on the degree of the cardiac anomalies.

PMID- 15505599
TI  - Enlarged cervical lymph nodes and elevated liver chemistry tests: a therapeutic
      dilemma.
AB  - We describe the case of a 36-years-old male patient, originating from India, who
      presented with enlarged cervical lymph nodes and elevated liver chemistry tests.
      Histologically necrosing granulomas were observed in the lymph nodes, and PCR
      revealed DNA from mycobacterium tuberculosis. However, in the liver biopsy
      granulomatous hepatitis without central necrosis was seen. With a positive PCR
      for mycobacteria from liver tissue and no evidence for other hepatic diseases we
      started drug treatment with standard quadruple regimen consisting of isoniazid,
      rifampicin, ethambutol, and pyrazinamide. Five days after onset of therapy, liver
      chemistry tests rose 10-fold, forcing us to interrupt treatment. Gradual step
      wise re-exposition with the same medication after return of liver chemistry tests
      to baseline was well tolerated without any further side effects. Liver
      involvement of tuberculosis can have many facets and may be treated by gradual
      dosing of standard drugs.

PMID- 15505604
TI  - The successful treatment of severe aplastic anemia with autologous cord blood
      transplantation.
AB  - Cord blood transplantation has been used extensively in the allogeneic setting
      for acquired and genetic disorders of hematopoiesis. There is less experience in
      the utility of autologous cord blood transplantation, and there is great
      controversy about the role of autologous cord blood collection and storage. We
      report on the successful use of autologous cord blood transplantation for the
      treatment of severe aplastic anemia following fulminant hepatic failure and
      living related liver transplantation.

PMID- 15505605
TI  - Temporal discordance between graft-versus-leukemia and graft-versus-host
      responses: a strategy for the separation of graft-versus-leukemia/graft-versus
      host reactivity?
AB  - The graft-versus-leukemia (GVL) effect is often coexpressed with graft-versus
      host disease (GVHD), although the temporal kinetics of these responses have not
      been critically examined. To evaluate this question in the absence of the
      confounding effects of the conditioning regimen, 23 patients who received donor
      lymphocyte infusions from HLA-identical siblings and subsequently developed GVHD
      and/or a GVL response were studied to determine whether these were temporally
      synchronous events. The GVL effect occurred significantly earlier than GVHD,
      being that 19 of 23 patients had a sustained GVL response that antedated the
      onset of clinical GVHD. The median difference between time to GVL and graft
      versus-host (GVH) reactivity in the entire cohort was 14 days. There was no
      correlation between total T-cell dose and the relative onset of GVL versus GVH
      reactivity, indicating that temporal dissociation of GVL and GVH responses was
      not a function of the absolute number of infused donor T cells. These data
      support existing murine bone marrow transplantation studies indicating that GVL
      and GVH responses are not temporally synchronous events and raise the possibility
      that targeted elimination of alloreactive donor T cells after bone marrow
      transplantation may be an effective strategy for the separation of GVL/GVH
      reactivity.

PMID- 15505606
TI  - Tracking ex vivo-expanded CD4+CD25+ and CD8+CD25+ regulatory T cells after
      infusion to prevent donor lymphocyte infusion-induced lethal acute graft-versus
      host disease.
AB  - Donor bone marrow (BM)-derived CD4+ CD25+ regulatory T cells, maturing in the
      host thymus, are critical in inhibiting graft-versus-host disease (GVHD) after
      donor lymphocyte infusion (DLI) in murine BM chimeras. Data presented here
      demonstrate that fresh CD25+ cells isolated from donor-type mice can be expanded
      ex vivo by a variety of methods. Ex vivo-expanded CD4+ CD25+ and CD8+ CD25+ cells
      were potent suppressors of donor response to host alloantigens in mixed
      lymphocyte reaction assays. Both fresh and ex vivo-expanded CD4+ CD25+ cells
      persisted long-term in vivo and effectively prevented DLI-induced GVHD in CD25-/-
      BM chimeras. Importantly, co-infused CD4+ CD25+ cells with DLI cells migrated to
      peripheral lymphoid organs and survived long-term in DLI-treated CD25-/-
      chimeras, but not in DLI-treated CD25+/+ chimeras, indicating homeostatic control
      of CD25+ cells and an available niche required for their long-term persistence.
      Furthermore, maintenance of CD25 expression seemed necessary for suppressive
      function, because only the CD25+ cell fraction, but not the CD25- fraction
      isolated after adoptive transfer, was suppressive in vitro. Ex vivo-expanded CD8+
      CD25+ cells weakly prevented GVHD, apparently because of a rapid disappearance of
      these cells after adoptive transfer. Taken together, these data suggest that the
      therapeutic use of ex vivo-expanded CD4+ CD25+ cells may be a feasible, nontoxic
      modality for controlling GVHD in the clinic. Because of strict homeostatic
      control, an available niche may be required for long-term persistence of infused
      regulatory T cells.

PMID- 15505607
TI  - A comparison of gene transfer and antigen-loaded dendritic cells for the
      generation of CD4+ and CD8+ cytomegalovirus-specific T cells in HLA-A2+ and HLA
      A2- donors.
AB  - Dendritic cells have been used effectively to select for human cytomegalovirus
      (CMV)-specific T cells for immunotherapy applications. The ability to process and
      present relevant major histocompatibility complex class I and II peptides to T
      cells makes them ideal for selecting CD4+ and CD8+ T cells regardless of HLA
      tissue type. This study compared the generation of CMV-specific T cells by using
      dendritic cells loaded with either CMV pp65495-503 peptide or CMV lysate or
      transduced with adenovirus encoding the pp65 gene (Ad5pp65GFP) for the generation
      of CD4+ and CD8+ CMV-specific T cells in HLA-A2+ and HLA-A2 - donors. In HLA-A2+
      donors, CD8+ tetramer+ T cells increased with all antigens but were greatest in
      peptide- and Ad5pp65GFP-stimulated T cells. The CD4+ /CD8+ ratio in the
      stimulated T-cell cultures proved to be dependent on the antigen used. CMV lysate
      stimulated cells were primarily CD4+, whereas peptide- and Ad5pp65GFP-stimulated
      cultures were mostly CD8+. Analysis of cells from lysate-stimulated or gene
      transduced-stimulated cultures showed expansion of CMV-specific CD4+ T cells,
      indicating that major histocompatibility complex class II peptides were present
      in both antigens. Furthermore, CMV-specific T cells were generated from HLA-A2 -
      donors by using Ad5pp65GFP transduction or CMV lysate stimulation and were able
      to recognize a pp65 peptide restricted to the HLA-B35 allele. These data indicate
      that either CMV lysate or adenovirus encoding CMV antigenic genes may be useful
      for the generation of both CD4+ and CD8+ CMV-specific T cells in donors
      irrespective of HLA tissue type and may be applicable to clinical immunotherapy.

PMID- 15505608
TI  - Superior depletion of alloreactive T cells from peripheral blood stem cell and
      umbilical cord blood grafts by the combined use of trimetrexate and interleukin-2
      immunotoxin.
AB  - Acute graft-versus-host disease, a major obstacle to the overall success of
      allogeneic hematopoietic stem cell transplantation, is primarily induced by a
      subset of donor T cells. Most strategies to prevent acute graft-versus-host
      disease target all T cells regardless of their specificity, and this leads to
      prolonged posttransplantation immunodeficiency. Selective depletion of
      alloreactive T cells could spare protective immunity and facilitate engraftment
      and graft-versus-leukemia effects. Recently described depletion strategies target
      activation markers such as CD25 that are expressed by alloreactive T cells.
      However, incomplete depletion may occur when a single surface epitope or pathway
      of apoptosis is targeted that may not be fully and concurrently expressed among
      all alloreactive cells. We now report on a novel strategy effective in both cord
      blood and peripheral blood stem cell alloreactive T cells that simultaneously
      induces 2 independent pathways of apoptosis after stimulation by recipient
      dendritic cells or Epstein-Barr virus-transformed B cells. First, we demonstrate
      that the folate antagonist trimetrexate selectively depletes proliferating
      alloreactive precursors in vitro in a dose- and time-dependent manner. Similarly,
      a second agent, denileukin diftitox, kills activated alloreactive T cells
      expressing CD25. Most importantly, these 2 agents can exert their effects in
      concert with superior efficacy while sparing resting bystander T cells, which
      remain available to mount antimicrobial or third-party responses.

PMID- 15505609
TI  - Unrelated donor hematopoietic stem cell transplantation for patients with
      hematologic malignancies using a nonmyeloablative conditioning regimen of
      fludarabine, low-dose total body irradiation, and rabbit antithymocyte globulin.
AB  - Hematopoietic stem cell chimerism can be established after low-dose conditioning
      regimens, although the risk of donor cell rejection increases for unrelated donor
      transplantations. We added pretransplantation rabbit antithymocyte globulin (6
      mg/kg) to an established conditioning regimen of fludarabine (90 mg/m2) and
      single-fraction total body irradiation (200 cGy) followed by postgrafting
      immunosuppression with cyclosporine A and mycophenolate mofetil for 22 patients
      with hematologic malignancies. One patient rejected the graft and successfully
      underwent transplantation with cells from a second donor by using the same
      conditioning regimen. The actuarial probability of developing acute graft-versus
      host disease grade II to IV before day 100 was 40%, although 9 of 14 patients who
      survived beyond 100 days developed chronic graft-versus-host disease. These data
      support a hypothesis that the addition of antithymocyte globulin decreases the
      risk of graft-versus-host and host-versus-graft reactions when combined with a
      nonmyeloablative conditioning regimen of fludarabine and total body irradiation.

PMID- 15505610
TI  - The use of high-dose cyclophosphamide, carmustine, and thiotepa plus autologous
      hematopoietic stem cell transplantation as consolidation therapy for high-risk
      primary breast cancer after primary surgery or neoadjuvant chemotherapy.
AB  - We assessed the 5-year results of a high-dose cyclophosphamide, carmustine, and
      thiotepa (CBT) regimen plus autologous hematopoietic stem cell transplantation
      (AHST) as an adjuvant consolidation therapy for high-risk primary breast cancer
      patients with > or =10 positive axillary lymph nodes after primary surgery or >
      or =4 positive axillary lymph nodes after neoadjuvant chemotherapy and surgery.
      The associations of various potential prognostic factors with the relapse-free
      survival (RFS) rate and overall survival (OS) rate were determined. Between
      October 1992 and March 2000, 177 eligible patients (median age, 46 years) were
      given high-dose CBT followed by AHST. At a median follow-up of 63 months, the
      acute treatment-related mortality was 4.5%. Estimated 5-year RFS and OS rates
      were 62% and 68%, respectively, for all patients. For patients with > or =10
      positive axillary lymph nodes after primary surgery, the 5-year RFS and OS rates
      were 71% and 70%, respectively, and for patients with > or =4 positive axillary
      lymph nodes after neoadjuvant chemotherapy, the 5-year RFS and OS rates were 53%
      and 66%, respectively. In 2-sided log-rank tests, earlier disease stage, a lower
      lymph node ratio, and a lower tumor score were associated with a prolonged RFS
      and OS. In a multivariate proportional hazards model, disease stage and lymph
      node ratio remained significant. We concluded that high-dose CBT with AHST for
      high-risk primary breast cancer is feasible, with comparable efficacy to other
      phase II studies. More than a 50% estimated 5-year survival rate was seen in all
      high-risk primary breast cancer patients. In accordance with results from recent
      randomized studies, we need to continue high-dose chemotherapy with AHST for
      patients with high-risk primary breast cancer in the phase III randomized
      setting.

PMID- 15505611
TI  - Pharmacokinetics and individualized dose adjustment of intravenous busulfan in
      children with advanced hematologic malignancies undergoing allogeneic stem cell
      transplantation.
AB  - We investigated the pharmacokinetics (PK) of a recently approved intravenous
      busulfan (IVBU) formulation as a part of the preparative regimen in 20 children
      with advanced hematologic malignancies undergoing allogeneic hematopoietic stem
      cell transplantation. Seventeen patients received a thiotepa, IVBU, and
      cyclophosphamide-based regimen, and 3 patients received an IVBU and
      cyclophosphamide-based regimen. All patients received IVBU 0.8 mg/kg for the
      first 2 doses; thereafter, the IVBU dose was modified, if required, to achieve a
      final area under the concentration-time curve (AUC) at steady state of 1150
      micromol/L/min per dose (range, 1000-1300 micromol/L/min per dose; SD +/-13%)
      based on the first-dose PK determination. PK studies were repeated on subsequent
      doses to verify the final AUC. Initial mean IVBU clearance and half-life were
      3.96 mL/min/kg and 1.98 hours, respectively. Sixteen (80%) of the 20 patients
      received dose adjustments: 14 patients required dose escalations, and 2 required
      dose reductions. Overall, thirteen (72%) of 18 available sample sets at final
      follow-up PK analysis showed the IVBU exposure to be within the targeted range.
      IVBU PK was linear, and interpatient variability was much lower than that
      observed with oral busulfan. IVBU was well tolerated, and no case of hepatic veno
      occlusive disease was encountered. Mild and transient hyperbilirubinemia was
      observed in 7 patients. Thirteen of the 20 patients were alive at a median follow
      up of 651 days (range, 386-1555 days). We conclude that a standardized IVBU dose
      of 0.8 mg/kg in children does not always result in an AUC within the reference
      range defined in this study. Therapeutic drug monitoring with dose adjustment
      based on first-dose PK can optimize the systemic busulfan exposure for children
      undergoing allogeneic hematopoietic stem cell transplantation.

PMID- 15505613
TI  - Academic psychiatry in Russia: new times, new challenges.

PMID- 15505617
TI  - Order and disorder in the vascular network.

PMID- 15505619
TI  - Polymorphisms in multidrug resistance 1 (MDR1) gene are associated with
      refractory Crohn disease and ulcerative colitis.
AB  - We used coding and noncoding polymorphisms evenly spaced across the ABCB1/MDR1
      gene to perform association analysis in Slovenian patients with inflammatory
      bowel diseases and to obtain haplotype structure and patterns of linkage
      disequilibrium (LD) in the MDR1 gene. A disease association study was performed
      in 307 IBD patients, including 144 patients with ulcerative colitis (UC) and 163
      patients with Crohn's disease (CD), and 355 healthy controls. Here we report an
      association between MDR1 alleles, polymorphisms and haplotypes and refractory CD
      patients, who do not respond to standard therapy, including patients who develop
      fistulas. We also report an association with UC and MDR1 polymorphisms in a
      Slovenian population. Haplotypes significantly associated with diseases were
      defined by single-nucleotide polymorphisms (SNPs) in exons 12 (1236 C>A),
      21(A893S), and 26 (3435 C>T). In addition, two intronic SNPs in LD with the
      disease haplotype, one in intron 13 (rs2235035) and another in intron 16
      (rs1922242), were significantly associated with refractory Crohn (P=0.026, odds
      ratio (OR) 2.7 and P=0.025, OR 2.8, respectively), as well as with UC (P=0.006,
      OR 1.8 and P=0.026, OR 1.9, respectively). Our results suggest that MDR1 is a
      potential target for therapy in refractory CD patients and in patients with UC.

PMID- 15505620
TI  - A new superinvasive in vitro phenotype induced by selection of human breast
      carcinoma cells with the chemotherapeutic drugs paclitaxel and doxorubicin.
AB  - Doxorubicin- and paclitaxel-selected variants of an in vitro invasive clonal
      population of the human breast cancer cell line, MDA-MB-435S, were established by
      pulse selection, and exhibited a novel 'superinvasive' phenotype. This phenotype
      is characterised by an ability to relocate to another surface following invasion
      through matrigel and membrane pores, by decreased adhesion to extracellular
      matrix proteins and by increased motility. This may represent an in vitro model
      of a step in the metastatic process occurring subsequent to invasion. The
      paclitaxel-resistant variants, MDA-MB-435S-F/Taxol-10p and MDA-MB-435S-F/Taxol
      10p4p were resistant to paclitaxel, vincristine and docetaxel, but not to
      doxorubicin, carboplatin, etoposide or 5-fluorouracil. The doxorubicin-selected
      variants MDA-MB-435S-F/Adr-10p and MDA-MB-435S-F/Adr-10p10p, in contrast,
      exhibited only small increases in resistance to doxorubicin, although they were
      slightly resistant to VP-16 and docetaxel, and exhibited increased sensitivity to
      paclitaxel, carboplatin and 5-fluorouracil.

PMID- 15505621
TI  - Phase II study of UFT and oxaliplatin in first-line treatment of advanced
      colorectal cancer.
AB  - The purpose of this study was to evaluate the efficacy, assessed as response
      rate, and toxicity of UFT (Tegafur-Uracil) in combination with oxaliplatin as
      first-line treatment of advanced colorectal cancer (CRC). In all, 84 patients
      with recurrent or metastatic CRC with measurable disease were included. Treatment
      consisted of oxaliplatin 85 mg m(-2) in 120-min intravenous (i.v.) infusion on
      days 1 and 15; i.v. l,leucovorin (l,LV) 250 mg m(-2) given in 2 h on day 1,
      followed by oral UFT 390 mg m(-2) on days 1-14, and oral l,LV 7.5 mg/12 h on days
      2-14. Cycles were repeated every 28 days. A total of 492 cycles of chemotherapy
      were delivered with a median of six per patient (range 1-12). There was one
      complete response (1%) and 28 partial responses (34%) for an overall response
      rate of 35% (95% confidence interval (CI): 24-46%). A total of 36 patients (44%)
      had stable disease, whereas 17 (21%) had a progression. The median time to
      progression was 7.3 months and the median overall survival was 16.8 months. A
      prescheduled preliminary analysis was performed after inclusion of 16 patients
      who detected a high gastrointestinal toxicity, which led to a reduction of the
      UFT dose to 300 mg m(-2). With this new dosage, grade 3-4 diarrhoea and grade 3-4
      nausea/vomiting dropped to 21 and 14% of patients, respectively. Other grade 3-4
      toxicities were stomatitis in one (1%), anaemia in three (5%), neutropenia in two
      (3%), thrombocytopenia in one(1%), fatigue in six (9%), peripheral sensory
      neuropathy in nine (14%) and laryngopharyngeal dysesthesia in two patients (2%).
      The combination of oxaliplatin and UFT-l,LV is an active, easy-to-administer
      regimen with moderate toxicity. Hence, this regimen is worthy of further
      investigation.

PMID- 15505622
TI  - Inhibition of AKT survival pathway by a small molecule inhibitor in human
      endometrial cancer cells.
AB  - The PTEN (phosphatase and tensin homolog deleted on chromosome 10) tumour
      suppressor is mutated in 40-50% of human endometrial cancers. PTEN exerts its
      effects in part via inhibition of the antiapoptotic protein AKT. We demonstrate
      that two endometrial cancer cell lines that harbour PTEN mutations, Ishikawa and
      RL95-2, have high levels of phosphorylated AKT and high AKT kinase activity. Two
      additional endometrial cancer cell lines that express wild-type PTEN, Hec1A and
      KLE, have little phosphorylated AKT and minimal demonstrable AKT kinase activity.
      We tested a potential inhibitor of the AKT pathway, API-59CJ-OMe, in these four
      cell lines. We found that API-59CJ-OMe inhibits AKT kinase activity and induces
      apoptosis in the Ishikawa and RL95-2 cell lines with high AKT activity, but has
      little effect on Hec1A and KLE cells without AKT activity. API-59CJ-OMe may
      therefore have therapeutic potential for those endometrial cancers that harbour
      PTEN mutations and AKT activation.

PMID- 15505623
TI  - Fenretinide stimulates redox-sensitive ceramide production in breast cancer
      cells: potential role in drug-induced cytotoxicity.
AB  - The synthetic retinoid N-(4-hydroxphenyl) retinamide (4HPR) has manifold actions,
      which may contribute to its chemopreventive effects on breast cancer cell growth
      and progression. A role for ceramide as a stress-response signal is investigated
      here during the cytotoxic action of 4HPR in MCF-7 cells. N-(4-hydroxphenyl)
      retinamide induced a dose-dependent decline in cell growth and survival
      associated with a maximal 10-fold increase in ceramide production at 10 microM. N
      (4-hydroxphenyl) retinamide exhibited a greater potency than all-trans retinoic
      acid (ATRA) on growth inhibition and ceramide production. The synthetic
      peroxisome proliferator-activated receptors agonist troglitazone (TGZ), but not
      the native ligand 15-deoxy-delta 12,14-prostaglandin J2, abrogated both these
      actions of 4HPR but not that of ATRA. The antioxidant N-acetylcysteine mimicked
      the abrogative effect of TGZ on 4HPR action, while the exogenous oxidant H2O2
      also stimulated ceramide production. The inhibitors of de novo ceramide
      synthesis, fumonisin B1 and myriocin, blocked the ceramide response to 4HPR and
      partially reversed the apoptotic response, but did not prevent the overall
      decline in cell survival. The pancaspase inhibitor Z-VAD fmk reduced the decrease
      in cell survival caused by 4HPR, but did not affect the ceramide response. These
      findings describe a novel redox-sensitive elevation of ceramide levels associated
      with the cytotoxic response of breast cancer cells to 4HPR. However, a major
      mediatory role for this sphingolipid in this context remains equivocal.

PMID- 15505624
TI  - The relationship between interleukin-6 and C-reactive protein in patients with
      benign and malignant prostate disease.
AB  - The relationship between interleukin-6 and C-reactive protein was evaluated in
      patients with benign (n=59) and malignant (n=86) prostate disease. The
      correlation coefficients for patients with benign prostatic disease and prostate
      cancer were rs=0.632, P<0.001 and rs=0.663, P<0.001, respectively. These results
      indicate that the relationship between interleukin-6 and C-reactive protein is
      similar in patients with benign and malignant prostate disease.

PMID- 15505625
TI  - Phase II clinical trial of capecitabine and gemcitabine chemotherapy in patients
      with metastatic renal carcinoma.
AB  - We report a single institution phase II study of gemcitabine 1200 mg m(-2) i.v.
      on days 1 and 8 and capecitabine 1300 mg m(-2) twice daily on days 1-14 of each 3
      week cycle in patients with metastatic renal carcinoma. Patients had a WHO
      performance status of 0, 1 or 2. Of the 21 enrolled patients, 19 had received
      prior immunotherapy or chemoimmunotherapy. All had progressive disease at study
      entry. In all,19 patients had multiple sites of disease. The median duration of
      metastatic disease was 12.3 months (range 1.2-78.1 months). Three of the 19
      evaluable patients achieved a partial response to treatment, with no complete
      responses, producing an objective overall response rate of 15.8% (95% CI, 3.4
      39.6%). The median time to disease progression was 7.6 months, and median overall
      survival was 14.2 months. Treatment was reasonably well-tolerated, neutropenia
      being the most frequently observed grade 3 or 4 toxicity, occurring in 57% of
      patients. Other side effects were consistent with the established toxicity
      profile of the two drugs, including diarrhoea, palmar-plantar erythema, fatigue,
      nausea, vomiting and infection. This combination of gemcitabine and capecitabine
      has modest activity in immunotherapy-refractory metastatic renal carcinoma with
      manageable toxicity.

PMID- 15505626
TI  - Phase II study of S-1 in patients with advanced biliary tract cancer.
AB  - The aim of this study was to investigate the efficacy and safety of an oral
      fluoropyrimidine derivative, S-1, in patients with advanced biliary tract cancer.
      Patients with pathologically confirmed advanced biliary tract cancer, a
      measurable lesion, and no history of radiotherapy or chemotherapy were enrolled.
      S-1 was administered orally (40 mg m(-2) b.i.d.) for 28 days, followed by a 14
      day rest period. A pharmacokinetic study was performed on day 1 in the initial
      eight patients. In all, 19 consecutive eligible patients were enrolled in the
      study between July 2000 and January 2002. The site of the primary tumour was the
      gallbladder (n=16), the extrahepatic bile ducts (n=2), and the ampulla of Vater
      (n=1). A median of two courses of treatment (range, 1-12) was administered. Four
      patients achieved a partial response, giving an overall response rate of 21.1%.
      The median time-to-progression and median overall survival period were 3.7 and
      8.3 months, respectively. Although grade 3 anorexia and fatigue occurred in two
      patients each (10.5%), no grade 4 toxicities were observed. The pharmacokinetic
      parameters after a single oral administration of S-1 were similar to those of
      patients with other cancers. S-1 exhibits definite antitumour activity and is
      well tolerated in patients with advanced biliary tract cancer.

PMID- 15505627
TI  - Psychosocial impact of breast/ovarian (BRCA1/2) cancer-predictive genetic testing
      in a UK multi-centre clinical cohort.
AB  - This multi-centre UK study assesses the impact of predictive testing for breast
      and ovarian cancer predisposition genes (BRCA1/2) in the clinical context. In the
      year following predictive testing, 261 adults (59 male) from nine UK genetics
      centres participated; 91 gene mutation carriers and 170 noncarriers. Self-report
      questionnaires were completed at baseline (pre-genetic testing) and 1, 4 and 12
      months following the genetic test result. Men were assessed for general mental
      health (by general health questionnaire (GHQ)) and women for general mental
      health, cancer-related worry, intrusive and avoidant thoughts, perception of risk
      and risk management behaviour. Main comparisons were between female carriers and
      noncarriers on all measures and men and women for general mental health. Female
      noncarriers benefited psychologically, with significant reductions in cancer
      related worry following testing (P<0.001). However, younger female carriers (<50
      years) showed a rise in cancer-related worry 1 month post-testing (P<0.05). This
      returned to pre-testing baseline levels 12 months later, but worry remained
      significantly higher than noncarriers throughout (P<0.01). There were no
      significant differences in GHQ scores between males and females (both carriers
      and noncarriers) at any time point. Female carriers engaged in significantly more
      risk management strategies than noncarriers in the year following testing (e.g.
      mammograms; 92% carriers vs 30% noncarriers). In the 12 months post-testing, 28%
      carriers had bilateral risk-reducing mastectomy and 31% oophorectomy.
      Oophorectomy was confined to older (mean 41 yrs) women who already had children.
      However, worry about cancer was not assuaged by surgery following genetic
      testing, and this requires further investigation. In all, 20% of female carriers
      reported insurance problems. The data show persistent worry in younger female
      gene carriers and confirm changes in risk management consistent with carrier
      status. Men were not adversely affected by genetic testing in terms of their
      general mental health.

PMID- 15505628
TI  - Investigation of the role of SDHB inactivation in sporadic phaeochromocytoma and
      neuroblastoma.
AB  - Germline mutations in the succinate dehydrogenase (SDH) (mitochondrial
      respiratory chain complex II) subunit B gene, SDHB, cause susceptibility to head
      and neck paraganglioma and phaeochromocytoma. Previously, we did not identify
      somatic SDHB mutations in sporadic phaeochromocytoma, but SDHB maps to 1p36, a
      region of frequent loss of heterozygosity (LOH) in neuroblastoma as well. Hence,
      to evaluate SDHB as a candidate neuroblastoma tumour suppressor gene (TSG) we
      performed mutation analysis in 46 primary neuroblastomas by direct sequencing,
      but did not identify germline or somatic SDHB mutations. As TSGs such as RASSF1A
      are frequently inactivated by promoter region hypermethylation, we designed a
      methylation-sensitive PCR-based assay to detect SDHB promoter region methylation.
      In 21% of primary neuroblastomas and 32% of phaeochromocytomas (32%) methylated
      (and unmethylated) alleles were detected. Although promoter region methylation
      was also detected in two neuroblastoma cell lines, this was not associated with
      silencing of SDHB expression, and treatment with a demethylating agent (5
      azacytidine) did not increase SDH activity. These findings suggest that although
      germline SDHB mutations are an important cause of phaeochromocytoma
      susceptibility, somatic inactivation of SDHB does not have a major role in
      sporadic neural crest tumours and SDHB is not the target of 1p36 allele loss in
      neuroblastoma and phaeochromocytoma.

PMID- 15505629
TI  - Real-time RT-PCR correlates with immunocytochemistry for the detection of
      disseminated epithelial cells in bone marrow aspirates of patients with breast
      cancer.
AB  - Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) is a technique
      with the potential of improving the quantification of disseminated epithelial
      cells (DEC) in haematological tissues due to its exquisite sensitivity. This
      sensitivity may lead to false positivity. Immunocytochemistry (ICC) is regarded
      as the standard methodology to diagnose DEC. In this study, detection with ICC
      was compared with quantitative real-time RT-PCR for CK-19 and mammaglobin (hMAM)
      mRNA in bone marrow (BM) of patients with metastatic breast cancer (MBC). Bone
      marrow was aspirated from 14 control patients and from 29 patients with MBC.
      Mononuclear cells (MNC) were isolated. Immunostaining was carried out with the
      Epimet kit. Quantitative PCR was performed on the ABI Prism 7700. The CK-19 and
      hMAM mRNA quantities were normalised against beta-Actin and calculated relative
      to a calibrator sample (relative gene expression). All controls were negative by
      ICC and for hMAM expression measured by RT-PCR, whereas the median RGE value for
      CK-19 was 0.57. For the MBC patients, the median RGE for hMAM was 0 and 10 out of
      25 (40%) tested positive. Median RGE for CK-19 was 2.9 and 20 out of 25 (80%)
      tested positive. With ICC, the median value was 1 stained cell per sample, and 15
      out of 24 (62%) samples were positive. A correlation was observed between CK-19
      and hMAM expression (r=0.7; P=0.0003), and between hMAM expression and ICC
      (r=0.6; P=0.003). CK-19 expression and ICC (r=0.9; P<0.0001) showed the strongest
      correlation. Reverse transcriptase-polymerase chain reaction for CK-19 resulted
      in a higher number of positive BM samples of patients with MBC than ICC. Since an
      excellent correlation is observed between ICC and RT-PCR, and RT-PCR is probably
      more sensitive with the advantage of being less observer dependent and thus also
      more easy to automate, we consider our quantitative real-time RT-PCR method as
      validated for the detection of DEC in the bone marrow of breast cancer patients.

PMID- 15505630
TI  - Mammography screening in the Netherlands: delay in the diagnosis of breast cancer
      after breast cancer screening.
AB  - In a prospective study we determined the frequency and causes of delay in the
      diagnosis of breast cancer after suspicious screening mammography. We included
      all women aged 50-75 years who underwent biennial screening mammography in the
      southern breast cancer screening region of the Netherlands between 1 January 1996
      and 1 January 2002. Clinical data, breast imaging reports, biopsy results and
      breast surgery reports were collected of all women with a positive screening
      result with a minimum of 2-year follow-up. Of 153 969 mammographic screening
      examinations, 1615 (1.05%) were positive screens. Breast cancer was diagnosed in
      770 (47.9%) of 1607 women for whom follow-up information was available, yielding
      a cancer detection rate of 5.0 per 1000 women screened. Breast cancer was
      diagnosed within 3 months following a positive screen in 722 cases (93.8%). The
      diagnostic delay was 4-6, 7-12 and 13-24 months, respectively, in 11 (1.4%), 24
      (3.1%) and nine (1.2%) patients. In four other patients (0.5%), breast cancer was
      diagnosed after a repeat positive screen, resulting in a diagnostic delay of 25
      27 months. Reasons for a diagnostic delay >3 months were erroneous mammographic
      interpretation of suspicious lesions as benign or probably benign lesions (33
      cases), benign biopsies from a malignant lesion (10), and omission to biopsy or
      remove a lesion that was suspicious at breast imaging (4) or core biopsy (1). We
      conclude that there is room for improvement in the workup of patients with a
      positive screening mammography, as seen from data in this screening region. To
      improve the workup, we suggest that other breast cancer screening programmes also
      identify delay in breast cancer diagnosis after a positive screen.

PMID- 15505631
TI  - GABAergic modulation of ventilatory response to acute and sustained hypoxia in
      obese Zucker rats.
AB  - OBJECTIVE: To determine whether altered central and/or peripheral gamma
      aminobutyric acid (GABA)ergic mechanisms acting in GABA(A) receptors contribute
      to the abnormal ventilatory response to acute and sustained hypoxia in obese
      Zucker rats. METHODS: In all, 10 lean and 10 obese Zucker rats were studied at 12
      weeks of age. Ventilation (V(.-)(E)), tidal volume (V(T)), and breathing
      frequency (f) during room air breathing and in response to sustained (30 min)
      hypoxic (10% O(2)) challenges were measured on three separate occasions by the
      barometric method following the randomized blinded administration of equal
      volumes of DMSO (vehicle), bicuculline methiodide (B(M), 1 mg/kg, peripheral
      GABA(A) receptor antagonist), or bicuculline hydrochloride (B(HCl), 1 mg/kg,
      peripheral and central GABA(A) receptor antagonist). RESULTS: Administration of
      B(M) and B(HCl) in lean animals had no effect on ventilation either during room
      air breathing or 30 min of sustained exposure to hypoxia. Similarly, B(M) failed
      to alter ventilation in obese rats. In contrast, B(HCl) significantly (P<0.05)
      increased V(.-)(E) and V(T) during room air breathing and 10-30 min of hypoxic
      exposure in obese rats. During 5 min of acute hypoxic exposure, V(T) remained
      elevated with B(HCl) in obese rats, but the V(.-)(E) appeared not to be increased
      with B(HCl) due to a decrease in f. CONCLUSION: Thus, endogenous GABA modulates
      both ventilation during room air breathing and ventilatory response to sustained
      hypoxia in obese, not in lean, Zucker rats by acting specifically on GABA(A)
      receptors located within the central, not peripheral, nervous system. However,
      endogenous GABA does not modulate ventilation but the pattern of breathing during
      acute hypoxia in obesity in a different manner from that during sustained
      hypoxia.

PMID- 15505632
TI  - Relationships between cigarette smoking, body size and body shape.
AB  - OBJECTIVE: To define relationships between smoking status, body mass index (BMI),
      waist and hip circumferences (WC, HC) and waist to hip ratio (WHR). DESIGN:
      Further analysis of the cross-sectional Scottish Health Survey 1998 data.
      SUBJECTS: Nationally representative sample of 9047 adults aged 16-74 y. RESULTS:
      Body mass index (BMI) was lower in current smokers and higher in ex-smokers
      (P<0.001) when compared with nonsmokers in the survey population as a whole.
      After adjustment for confounding factors (age, social class, physical activity
      and alcohol intake), these differences still remained. However, examination of
      age categories showed no such differences in BMI between current smokers and
      nonsmokers in men aged 16-24 y or women aged below 55 y. In the age category 16
      24 y, prevalence of cigarette smoking was highest at 51% (men) and 43% (women) in
      obese subjects and lowest at 35% (men) and 33% (women) in people with BMI of 25
      30 kg/m(2). For women current smokers, mean WC and WHR were higher and HC was
      lower compared with nonsmokers (P<0.001). In men, only HC was lower in current
      smokers compared with nonsmokers for the entire sample (P<0.001). CONCLUSION:
      Cigarette smoking is associated with a lower BMI in adults over 24 y particularly
      in men, but not in younger people. In women, smoking is linked to the development
      of central adiposity. The gender-related central adiposity of men is not further
      increased by smoking, but a lower HC could suggest a reduction in muscle mass.

PMID- 15505633
TI  - Association of leptin levels with obesity and blood pressure: possible common
      genetic variation.
AB  - OBJECTIVE: To ascertain the extent to which relationships between obesity (OB)
      and blood pressure (BP) can be explained by an individual's leptin plasma levels.
      DESIGN: Pedigree-based cross-sectional study in an apparently healthy population
      of European origin. SUBJECTS: The study sample is comprised of 90 nuclear and
      more complex families totaling 210 male and 213 female subjects aged 18-75 y,
      randomly recruited in Bashkorstan Autonomic region, Russia. MEASUREMENTS: Various
      fatness and fat distribution traits (including nine circumferences (CRCs), and
      eight skinfolds (CKFs) by anthropometry), blood pressure, and plasma leptin
      levels (by ELISA kits). RESULTS: Adjustment for circulating leptin led to
      attenuation of the magnitude of correlations between OB and BP, regardless of
      trait pair and sex cohort. Some of these correlations became statistically
      nonsignificant. All familial effects were gone, and heritability estimates became
      virtually zero after adjustment of each of the OB traits and systolic blood
      pressure (SBP) in offspring for leptin values in parents. CONCLUSION: BP and OB
      covariation is substantially mediated by circulating leptin levels. As a result,
      body fat has only a weak independent effect on BP variation after adjustment for
      leptin levels. Our findings also strongly suggest that genetic variation in body
      mass index, SKFs, and even body CRCs, as well as of SBP is due to genetic
      variation of leptin. Genetic variation of diastolic blood pressure in the present
      sample, however, shared very little with that of leptin.

PMID- 15505634
TI  - The dual burden household and the nutrition transition paradox.
AB  - OBJECTIVE: The purpose of this study is to document the prevalence of households
      with underweight and overweight persons (henceforth referred to as dual burden
      households) and their association with income and urban residence. The
      explorations by urban residence and income will test whether dual burden
      households differ from 'underweight only' and 'overweight only' households,
      respectively. These comparisons are relevant to differentiating or adapting
      nutrition-related interventions wherever obesity and undernutrition cluster at
      the household level. POPULATION: Data analysis is based on national surveys
      conducted in Brazil, China, Indonesia, the Kyrgyz Republic, Russia, Vietnam and
      the United States. METHODS: All persons were first classified into categories for
      underweight and overweight, using body mass index (BMI) cutoffs, and then all
      households were categorized into four types: dual burden, overweight, underweight
      and normal. Income and urban residence were explored as key risk factors for
      being a dual burden household, with the effects modeled separately for each
      country. Multiple logistic regression was used to explore income and urban risk
      factors, controlling for household size, region of residence and either urban
      residence or income, as appropriate. RESULTS: In six of the countries studied, 22
      66% of households with an underweight person also had an overweight person.
      Countries with the highest prevalence of dual burden households were those in the
      middle range of gross national product (GNP). The dual burden household is easily
      distinguished from the 'underweight only' households in Brazil, China, Indonesia,
      the United States and Vietnam. In these five countries dual burden households
      were more likely to be urban and more likely to be among the highest income
      tertile. There were no significant differences between dual burden and
      'underweight only' households in Russia and the Kyrgyz Republic. In contrast,
      dual burden households were not easily distinguished from the 'overweight only'
      households in China, Indonesia, the Kyrgyz Republic, the United States and
      Vietnam. In Brazil and Russia dual burden households were more likely to be lower
      income and urban than 'overweight only' households. CONCLUSION: The prevalence of
      dual burden households presents a significant public health concern, particularly
      for those countries in the middle range of GNP. In some countries (China,
      Indonesia, the Kyrgyz Republic, the United States and Vietnam), dual burden
      households share sociodemographic profiles with overweight households, raising
      concerns for underweight individuals who may inadvertently become the focus of
      obesity prevention initiatives. For this reason, obesity prevention efforts
      should focus on messages that are beneficial to the good health of all, such as
      increasing fruit and vegetable intake, improving overall diet quality and
      increasing physical activity.

PMID- 15505635
TI  - Sustained increase in dietary oleic acid oxidation following morning exercise.
AB  - OBJECTIVE: We have previously reported that prior exercise increases the
      oxidation of dietary monounsaturated fat in comparison to rest when the fat is
      given in a mixed meal 30 min following the completion of exercise. In this study,
      we determined whether the increase in dietary fat oxidation after exercise
      persisted when the time between exercise and fatty acid administration was
      lengthened. DESIGN: Six female subjects (age=24+/-0.1 y, BMI=21+/-1 kg/m2) were
      recruited for a total of six visits each. During three visits, a stationary cycle
      exercise session (1250 kJ) was performed at 65% VO2 peak in a whole-body
      calorimeter; while during three other visits, exercise was replaced with rest.
      Subjects received [1-13C]oleate and [d31]palmitate with a different meal at each
      visit: breakfast, lunch, and dinner. RESULTS: Dietary oleate oxidation following
      prior rest did not differ between dose times and was 36+/-3, 42+/-5, and 42+/-3%
      for the 13 h following breakfast, lunch, and dinner. Prior exercise resulted in
      greater oleate oxidation following all dose times than prior rest (P<0.01) being
      52+/-4, 64+/-3, and 53+/-3% for the breakfast, lunch, and dinner dose. The
      oxidation was significantly greater following lunch than the other dose times
      (P<0.05). Prior exercise (1250 kJ) did not result in greater oxidation of
      palmitate; however, oxidation following prior exercise increased with later dose
      times (13+/-2, 23+/-2, and 23+/-3% for breakfast, lunch, and dinner; P<0.05) and
      following rest (18+/-2, 22+/-2, and 27+/-2% for breakfast, lunch, and dinner;
      P<0.005). CONCLUSIONS: The increase in oleate oxidation when administered after
      early morning exercise was found to persist for all three meals of the day, with
      the greatest effect occurring for the lunch meal. Palmitate oxidation, while
      apparently resistant to the effects of 1250 kJ of prior exercise, increases when
      administered later in the day, suggesting a diurnal variation in the oxidation of
      dietary fatty acids. These results demonstrate that prior exercise selectively
      alters the partitioning of dietary fatty acids. Furthermore, these findings
      demonstrate additional benefits of substituting monounsaturated for saturated
      fatty acids in the diet.

PMID- 15505636
TI  - Insulin downregulates M(2)-muscarinic receptors in adult rat atrial
      cardiomyocytes: a link between obesity and cardiovascular complications.
AB  - OBJECTIVE: To determine whether decreased cardiac parasympathetic activity
      observed in obesity is due to insulin-induced alterations in cardiac M(2)
      muscarinic receptors and/or adenylyl cyclase activity. DESIGN AND METHODS: After
      incubation with increasing concentrations of insulin, adult rat atrial
      cardiomyocytes were assayed for M(2)-muscarinic receptor binding density and
      affinity, and for M(2)R mRNA expression using RT-PCR analysis. Forskolin
      stimulated adenylyl cyclase activity and its inhibition by carbachol were also
      assayed, as was endothelial nitric oxide synthase mRNA expression. The effects of
      insulin on M(2)-muscarinic receptor density and mRNA expression levels were
      analyzed using the insulin signaling inhibitors rapamycin, wortmanin and PD
      098059. RESULTS: Insulin induces a concentration- and time-dependent decrease in
      expression of the M(2)R mRNA, and in [(3)H]N-methylscopolamine binding by the
      receptor. These effects on the M(2)R mRNA levels and on [(3)H]N-methylscopolamine
      binding were prevented by PD 98059, but not by wortmanin or rapamycin. Basal and
      forskolin-induced cAMP production did not differ, but the inhibition of forskolin
      simulated enzyme activity by carbachol was blunted by insulin. No change in the
      mRNA levels for endothelial nitric oxide synthase was observed. CONCLUSION: In
      rat atrial cardiomyocytes, insulin markedly alters both the M(2)-muscarinic
      receptor density, and its mRNA expression through transcriptional regulation and
      adenylyl cyclase activity. These data suggest that the obesity-associated
      decrease in cardiac parasympathetic tone may be related to hyperinsulinemia,
      which could directly contribute to cardiovascular morbidity in obese patients.

PMID- 15505637
TI  - Effect of glycemic index on whole-body substrate oxidation in obese women.
AB  - BACKGROUND: Glycemic index is hypothesized to determine fuel partitioning through
      serum plasma insulin modifications induced by dietary carbohydrates, thereby
      modulating fat accretion or oxidation. OBJECTIVE: To assess the glycemic effects
      on postprandial fuel oxidation and blood response. DESIGN: In all, 12 obese women
      were fed on a randomized crossover design with two test meals (breakfast+lunch).
      High- or low-glycemic meals were provided on separate days. Energy intake on high
      glycemic meal was 7758+/-148 kJ and for low-glycemic meal was 7806+/-179 kJ.
      Carbohydrates supplied were 273+/-5 and 275+/-6 g, respectively. Macronutrient
      distribution was 55% carbohydrates, 30% fat and 15% protein. Fuel oxidation was
      measured continuously in a respiratory chamber for 10 h. Serum glucose, free
      fatty acids (FFA), insulin and glucagon samples were taken for 5 h after
      breakfast. RESULTS: Glucose AUC changed significantly in response to different
      glycemic breakfast. Low- vs high-glycemic breakfast was 211+/-84 and 379+/-164
      mmol/l (P<0.05). Similarly, insulin changed from 94+/-37 and 170+/-87 nmol/l
      (P<0.05), respectively. The rate of increment for serum glucose and insulin
      reached by the high- vs low-glycemic meal was 1.8 times more with the high
      glycemic breakfast. Serum FFA were similarly suppressed by both meal types by 3 h
      after meal intake, but then raised significantly more with the low-glycemic meal
      by the fourth and fifth hour (P<0.05). Plasma glucagon did not show a significant
      variation with glycemic index. Carbohydrate and fat oxidation was not modified by
      glycemic meal characteristics, being virtually the same for low- vs high-glycemic
      comparisons in the 5 h following breakfast and lunch (P=NS). CONCLUSION: This
      study demonstrates that dietary glycemic characteristics were unable to modify
      fuel partitioning in sedentary obese women.

PMID- 15505638
TI  - Separate and interacting effects within the catechol-O-methyltransferase (COMT)
      are associated with schizophrenia.
AB  - Several lines of evidence have implicated the catechol-O-methyltransferase (COMT)
      gene as a candidate for schizophrenia (SZ) susceptibility, not only because it
      encodes a key dopamine catabolic enzyme but also because it maps to the
      velocardiofacial syndrome region of chromosome 22q11 which has long been
      associated with SZ predisposition. The interest in COMT as a candidate SZ risk
      factor has led to numerous case-control and family-based studies, with the
      majority placing emphasis on examining a functional Val/Met polymorphism within
      this enzyme. Unfortunately, these studies have continually produced conflicting
      results. To assess the genetic contribution of other COMT variants to SZ
      susceptibility, we investigated three single-nucleotide polymorphisms (SNPs)
      (rs737865, rs4633, rs165599) in addition to the Val/Met variant (rs4680) in a
      highly selected sample of Australian Caucasian families containing 107 patients
      with SZ. The Val/Met and rs4633 variants showed nominally significant
      associations with SZ (P<0.05), although neither of the individual SNPs remained
      significant after adjusting for multiple testing (most significant P=0.1174).
      However, haplotype analyses showed strong evidence of an association; the most
      significant being the three-marker haplotype rs737865-rs4680-rs165599 (global
      P=0.0022), which spans more than 26 kb. Importantly, conditional analyses
      indicated the presence of two separate and interacting effects within this
      haplotype, irrespective of gender. In addition, our results indicate the Val/Met
      polymorphism is not disease-causing and is simply in strong linkage
      disequilibrium with a causative effect, which interacts with another as yet
      unidentified variant approximately 20 kb away. These results may help explain the
      inconsistent results reported on the Val/Met polymorphism and have important
      implications for future investigations into the role of COMT in SZ
      susceptibility.

PMID- 15505640
TI  - TGFBR1*6A is not associated with prostate cancer in men of European ancestry.
AB  - The TGFBR1*6A (*6A) variant in exon 1 of the TGFBR1 gene has been postulated as a
      putative tumor susceptibility allele in several studies. We have performed a case
      control study in 537 men with histologically verified prostate cancer and in 488
      unrelated controls to investigate the association of *6A with prostate cancer.
      Our results revealed that the frequency of the (*)6A allele does not differ in
      men with prostate cancer compared to healthy controls, even in a subset of age
      matched cases and controls. There is no compelling evidence for an association of
      the *6A variant with prostate cancer.

PMID- 15505639
TI  - GAD1 (2q31.1), which encodes glutamic acid decarboxylase (GAD67), is associated
      with childhood-onset schizophrenia and cortical gray matter volume loss.
AB  - Postmortem brain studies have shown deficits in the cortical gamma-aminobutyric
      acid (GABA) system in schizophrenic individuals. Expression studies have shown a
      decrease in the major GABA-synthesizing enzyme (glutamic acid decarboxylase
      (GAD67) mRNA levels in neurons in dorsolateral prefrontal cortex in
      schizophrenics relative to controls. In the present study, SNPs in and around the
      GAD1 gene, which encodes the protein GAD67, were tested on a rare, severely ill
      group of children and adolescents with childhood-onset schizophrenia (COS)
      (n=72), in a family-based association analysis. Compared to adult-onset samples,
      the COS sample has evidence for more salient familial, and perhaps genetic, risk
      factors for schizophrenia, as well as evidence for frontal cortical hypofunction,
      and greater decline in cortical gray matter volume on anatomic brain MRI scans
      during adolescence. We performed family-based TDT and haplotype association
      analyses of the clinical phenotype, as well as association analyses with
      endophenotypes using the QTDT program. Three adjacent SNPs in the 5' upstream
      region of GAD1 showed a positive pairwise association with illness in these
      families (P=0.022-0.057). Significant transmission distortion of 4-SNP haplotypes
      was also observed (P=0.003-0.008). Quantitative trait TDT analyses showed an
      intriguing association between several SNPs and increased rate of frontal gray
      matter loss. These observations, when taken together with the positive results
      reported recently in two independent adult-onset schizophrenia pedigree samples,
      suggest that the gene encoding GAD67 may be a common risk factor for
      schizophrenia.

PMID- 15505641
TI  - Genetic susceptibility to tardive dyskinesia in chronic schizophrenia subjects:
      I. Association of CYP1A2 gene polymorphism.
AB  - Understanding the pharmacogenetic basis of developing iatrogenic disorders such
      as Tardive Dyskinesia (TD) has significant clinical implications. CYP1A2, an
      inducible gene of the cytochrome P450 family of genes, has been suggested to
      contribute to the metabolism of typical antipsychotics in subjects with
      schizophrenia on long-term treatment, and has been considered as a potential
      candidate gene for development of TD. In this study, we have investigated the
      significance of CYP1A2 gene polymorphisms in TD susceptibility among chronic
      schizophrenia sufferers (n=335) from north India. TD was diagnosed in
      approximately 29% (96/335) of these subjects. Of the 96 TD positives, 28 had been
      treated with typical antipsychotics alone, 23 with atypical antipsychotics alone
      and 45 patients had received both classes of drugs during the course of their
      illness. Out of the six SNPs tested, CYP1A2(*)2, (*)4, (*)5, (*)6 were found to
      be monomorphic in our population. CYP1A2(*)1C and CYP1A2(*)1F were polymorphic
      and were analyzed in the study sample. Since these two allelic variants lead to
      lesser inducibility among smokers, the smoking status of TD patients was also
      considered for all subsequent analysis. We observed increased severity of TD
      among TD-Y smokers, who were carriers of CYP1A2(*)1C (G>A) variant allele and had
      received only typical antipsychotic drugs (F(1,8)=9.203, P=0.016). No significant
      association of CYP1A2(*)1F with TD was observed irrespective of the class of drug
      they received or their smoking status. However, we found a significant
      association of CYP1A2(*)1F with schizophrenia (chi(2)=6.572, df=2, P=0.037).

PMID- 15505642
TI  - Renin-angiotensin system gene polymorphisms: relationship with blood pressure and
      microalbuminuria in telmisartan-treated hypertensive patients.
AB  - This study analyzed the relationship between four renin-angiotensin system (RAS)
      gene polymorphisms and the response to blood pressure lowering and development of
      microalbuminuria in 206 patients with essential hypertension treated once daily
      for 12 months with telmisartan 80 mg. Seated cuff blood pressure and urinary
      albumin excretion (UAE) were measured throughout the study. Patients were
      screened for the presence of the A-6G variant of the angiotensinogen gene,
      angiotensin-converting enzyme insertion/deletion polymorphism, and the A1166C and
      C573T polymorphisms of the angiotensin II type 1 receptor gene. No significant
      association was found between the presence of any gene polymorphism and the
      reduction of blood or UAE following telmisartan treatment. The results indicate
      that these RAS gene polymorphisms do not affect the antihypertensive activity and
      renoprotection in mild-to-moderate hypertensive patients treated with
      telmisartan.

PMID- 15505643
TI  - Association study of myo-inositol monophosphatase 2 (IMPA2) polymorphisms with
      bipolar affective disorder and response to lithium treatment.
AB  - Lithium is the most effective mood-stabilizing drug in the therapy of bipolar
      affective disorder (BP). It is thought to exert its effect via the
      phosphatidylinositol signalling system. Myo-inositol monophosphatase 2 (IMPA2)
      codes for an enzyme in this system that is inhibited by lithium. It is located on
      18p11.2, a region implicated as a BP susceptibility locus. We examined eight
      single-nucleotide polymorphisms (SNPs) identified within this gene for
      association with BP, using 237 parents-offspring trios and in 174 cases and 170
      controls. No SNP showed association with BP. When good responders to lithium
      treatment were compared with the poor responders, some statistically significant
      differences emerged for two SNPs; however, the sample became too small to draw
      definitive conclusions. We cannot find support for the involvement of variation
      in IMPA2 in susceptibility to bipolar disorder, but the role of this and other
      genes from the phosphoinositol signalling pathway in predicting response to
      lithium treatment merits further investigation.

PMID- 15505644
TI  - Cardiovascular changes during halothane induction in children.
AB  - OBJECTIVES: The incidence of bradycardia and myocardial depression following
      halothane induction in children is well documented. Bradycardia leads to reduced
      cardiac output, which can result in compromised organ perfusion. Halothane may
      sometimes induce arrhythmia. There is at present no study in this sub-region on
      the cardiovascular changes of halothane induction in children. This study was
      designed to investigate the cardiovascular changes and incidence of arrhythmias
      following halothane induction. PATIENTS AND METHODS: Ninety ASA I - II children
      aged 6 months to 12 years were studied. Premedication with oral promethazine
      1mg/kg was given to all patients above the age of one year. Anaesthesia was
      achieved with incremental halothane up to 3% in 33% oxygen and nitrous oxide.
      Halothane induction led to a significant drop in SBP, DBP and MAP in all patients
      at the end of induction. (p < 0.005). Heart rate values were significantly less
      postinduction in children older than one year (p < 0.05). Arrhythmias occurred in
      3.3% of all patients. No patient experienced bradycardia. Other complications
      included hypotension (8.8% ) and mild laryngeal spasm (2.2% ). RESULTS: Halothane
      induction in children results in significant reduction in heart rate and blood
      pressure. Bradyarrhthmias are uncommon with promethazine premedication.

PMID- 15505645
TI  - Efficacy of natural honey in the healing of leg ulcers in sickle cell anaemia.
AB  - In order to assess the reported efficacy of natural honey in the healing of
      chronic ulcers, the efficacy of locally applied natural honey was compared to
      that of Eusol solution in an open trial involving 20 patients with sickle cell
      anaemia (SS) who were in steady clinical states and had chronic leg ulceration.
      All patients were admitted to hospital for the 4 week duration of the trial for
      bed rest, daily aseptic dressings, and weekly measurement of the size of the
      ulcer. Fifteen patients with a total of 19 leg ulcers were evaluable at the end
      of the trial. Eleven ulcers were dressed with honey while 8 were dressed with
      Eusol. No significant differences were found in rates of healing of the ulcers in
      either treatment groups. This trial does not support the suggestion that natural
      honey is superior to Eusol in the healing of chronic sickle cell leg ulceration.

PMID- 15505646
TI  - Using verbal autopsy to identify and proportionally assign cause of death in
      Ibadan, southwest Nigeria.
AB  - Reliable and accurate data remain scarce on the cause and rates of mortality
      among adults in sub-Saharan Africa. The Idikan Adult Mortality Study, a
      prospective community-based study was initiated in order to obtain the overall as
      well as cause-specific mortality data for a community of adults (15 years and
      above). Standardised verbal autopsy questionnaire was used to investigate and
      assign the mode and cause of death. There were 232 reported deaths in the
      baseline population of 4127 adults over 5 years, giving an unadjusted death rate
      of 11.2 per 1000 per year. Thirty-nine (16.8% ) of these death occurred suddenly.
      The commonest known cause of death was due to cardiovascular disease, which was
      responsible for 43 (18.5% ) of all deaths. It was also the commonest known cause
      of sudden death accounting for 30.8% of such deaths. Infection was responsible
      for 28 (12.1% ) deaths while injury accounted for 7 (2.6% ) deaths. Subjects, 50
      years and above were more likely to die and also die suddenly than were the
      younger subject (p<0.0001, p<0.0001) and significantly more death occurred in
      males than females (6.9% versus 4.7% ) (P<0.01). Deaths were also more likely to
      have occurred at home and outside the hospital, increasing the probability of
      these deaths being underreported. Following multivariate logistic regression
      analysis, respondents between the age of 20 -49 years had significantly reduced
      risk of dying (p=0.029), while cigarette smoking significantly increased the risk
      of dying (p=0.012). In the absence of the urgently needed vital statistics, use
      of verbal autopsies is a potentially useful investigative method for identifying
      and assigning cause of adult deaths in a community.

PMID- 15505647
TI  - Determination of paternity disputes in the Niger delta region of Nigeria.
AB  - Results of paternity test, among disputants, carried out in our hospital between
      May 1992 and May 2002 were analysed. The cases were referred from Social Welfare
      Office, the Court and the Police. A total of twenty-four (24) cases consisting of
      22 (91.7% ) groups of three each, including the disputed child, the mother, and
      the alleged father; and 2 (8.3% ) groups of four each, with one group consisting
      of the disputed child, the mother and two alleged fathers, while the other
      consisting of the mother, the alleged father and the disputed female twins. All
      the disputed victims were children (10 males and 14 females) in the age group 6
      months to 8 years. The total cumulative paternal exclusion rate with our routine
      techniques was only 16.7% , all with the ABO blood group system. This is a far
      cry from the exclusion rates of about 97% for HLA testing, and 99.9% for DNA
      analysis. The available screening package in our hospital is therefore
      inadequate, and we advocate for the provision of more sophisticated and reliable
      techniques in designated centres across the country. This will go a long way in
      resolving the medicolegal and social problems encountered by the disputants and
      the victims.

PMID- 15505648
TI  - Holt-Oram syndrome with hypoplastic left heart syndrome in an African child.
AB  - This report illustrates the rare association of Holt-Oram syndrome with
      hypoplastic left heart syndrome hitherto unreported in an African child. The
      above association is highlighted as this child and the only other case reported
      in a Caucasian were diagnosed post mortem. The need for early cardiovascular and
      genetic evaluation or simple detailed family history to aid counselling is also
      emphasised.

PMID- 15505649
TI  - Clinical manifestations of myasthenia gravis - review of cases seen at the Lagos
      University Teaching Hospital.
AB  - OBJECTIVE: to review cases of myasthenia gravis at the Lagos University Teaching
      Hospital. METHODS: features of 27 cases of myasthenia gravis seen at the
      Neurology outpatient clinic of the Lagos University Teaching Hospital between
      January 1995 and December 2000 were reviewed using a uniform protocol. RESULTS:
      peak age incidence was in the third decade, and the male to female ratio 1.7 to
      1. The commonest presentation was ptosis (85.1% ), followed by diplopia (37% )
      and limb weakness (37% ). Other features such as dysphonia, dysphagia and
      dysarthria, were relatively uncommon. Ocular myasthenia gravis was diagnosed in
      half of the patients and generalised myasthenia in the other half. All the
      patients except four responded satisfactorily to prednisolone and/or anti
      cholinesterase. Azathioprine was added to the treatment of those that did not
      respond well, and replaced prednisolone in a patient who developed steroid
      induced diabetes mellitus. One patient developed myasthenic crisis and required
      artificial ventilator support. One patient had thymectomy. CONCLUSION: cases of
      myasthenia gravis present infrequently at the neurology clinic of the Lagos
      University Teaching Hospital. Clinical presentation and response to treatment are
      similar to those described elsewhere.

PMID- 15505650
TI  - Patterns of presentation and mortality in tetanus: a 10-year retrospective
      review.
AB  - BACKGROUND: Tetanus, an ubiquitous disease still ravages our population despite
      the fact that it is totally preventable. The mortality had remained high with its
      attendant socio-economic implications as it affects mainly farmers in their prime
      of life. We conducted this retrospective review to be able to determine pattern
      of presentation, case fatality rate and factors influencing mortality with a view
      to mapping out control strategies. PATIENTS, MATERIALS AND METHODS: The case
      records of all managed patients aged 16 and above over a ten-year period (1992
      2001) were retrieved and socio-demographic and clinical data as well as results
      of laboratory investigations were collated. Analysis was done using SPSS package.
      Chi-square analysis and student t-test were used for comparison of means as
      appropriate. P-values of <0.05 were taken as significant. RESULTS: There were a
      total of 114 patients managed during the period, which comprised 85 males and 29
      females. The mean age (+/- SD) was 35.96 years (+/- 17.76). Sixty-six (57.89% )
      patients are either jobless or farmers. Majority of the patients had injuries in
      the lower limb (59.65% ) when compared with 20.18% that had theirs in the upper
      limb. 107 (93.86% ) of the patients presented with trismus while only 82 (71.93%
      ) had opsthotomus. Only 51 (44.73% ) patients survived while 61(53.5% ) died. The
      mean age (+/- SD) of the survivors was 32.35 (+ 14.45) years while that of those
      that died was 39.4 (+/- 19.89) years (P = 0.036). Other factors that
      significantly influenced survival included severity of spasms (P = 0.003),
      tachycardia (P = 0.044), and degree of sedation (P<0.0001). No association was
      found between survival and incubation period, period of onset, site of injury and
      associated medical conditions. CONCLUSIONS: Tetanus is still associated with high
      mortality rate. Factors such as severity of spasms, age, sedation and tachycardia
      were found to significantly influence mortality. It is recommended that
      prophylactic life immunisation against tetanus be given to all Nigerians.

PMID- 15505651
TI  - Ocular findings in sickle cell disease patients in Lagos.
AB  - Sickle cell disease has varied manifestations in all systems of the body, ocular
      manifestations can be severe and sudden blindness may result amidst other
      complications. The study aims at determining the ocular findings in patients with
      sickle cell anaemia (HbSS) and sickle cell haemoglobin C disease (HbSC). 99
      subjects were recruited into the study carried out at the Lagos University
      Teaching Hospital over a 2 year period. A structured interview questionnaire was
      administered and physical examination was carried out at the Medical Out
      Patients' Sickle Cell Clinics. Subsequently in the (Guinness) Eye centre,
      examination for ocular manifestations was carried out using Snellen's chart, Slit
      light microscopy, direct and indirect ophthalmoscopy under mydriasis (with Gutt
      Tropicamide 1% , epinephrine 10% ) as well as tonometry and gonioscopy. The age
      of the 99 (51 males, 48 females) patients ranged from 13 to 43 years with a mean
      +/-SD of 20.42 +/- 6.13. There were 88 (88.9% ) SS and 11 (11.1% ) SC patients.
      The male to female ratio was 1.1: 1. Normal vision was present in 95 (96% ) of
      the patients [86 (97.8% ) SS and 9 (81.8% ) SC] while 4 (4.0% ) of the patients
      [2 (2.2% ) SS and 2 (18.2% ) SC] had impaired vision. Of the complaints, blurred
      vision was found in 12 (13.6% ) SS and one (9.0% ) SC patients. Itching of the
      eyes was found in 15 (17.0% ) SS and 3 (27.3% ) SC patients. Icterus was found in
      50 (50.5% ), conjunctival signs were found in 49 (49.5% ), retinal vascular
      tortuosity was in 12 (12 .10% ), peripheral retinal degeneration was in 5 (5% ),
      iridescent spots was in 3 (3% ) and optic atrophy in 2 (2% ) patients. The
      tortuosity of major fundus vessels were graded into 4 according to Hook and
      Cooper's criteria 87 (87.9% ) of the patients were in grade 0. The conjunctival
      vessels anomalies were classified into 5 grades (criteria of Sergeant). 37 (37.5%
      ) were in grade 0, 35 (35.3% ) in grade 1, 8 (8.1% ) in grade 2, 7 (7.1% ) in
      grade 3 and 12 (12.1% ) in grade 4. Conjunctival abnormalities occur commonly
      while proliferative retinopathy and optic atrophy were uncommon in sickle cell
      disease patients in Lagos. Further studies are required with a larger number of
      subjects to investigate the low incidence of proliferative retinopathy and optic
      atrophy in Lagos.

PMID- 15505653
TI  - One year of EEG unit at psychiatric hospital, Yaba, Lagos.
AB  - To show the continuous investigative value of electroencephalography (EEG) in the
      management of neuro-pathological disorders such as epilepsy in Nigeria. The
      limitation against this, especially lack of adequate fund to procure the EEG
      machine was highlighted. A prospective study over the first twelve months of
      setting up the EEG unit at the psychiatric hospital, Yaba, Lagos. Subjects
      included all the patients that had EEG recording in the unit during the study
      period. Awake EEG was done on each subject using 10-20 system of electrode
      placement with metal disc electrodes on the 24-channel medelec computerised EEG
      machine. Majority of the cohort (71.3% ) were aged < 30 years. Seizure disorder
      constituted the largest clinical reason for EEG request. The EEG findings were
      normal in close to 44% of the cohort, but abnormal in 56% with 'epileptiform
      activities' as the most common abnormalities. Despite the notable constraints
      involved, EEG continues to be of immense value in the management of neuro
      pathological disorders in Nigeria.

PMID- 15505652
TI  - The use of buccal fat pad in oral reconstruction - a review.
AB  - AIM: The aim of this article is to review the applications of the buccal fat pad
      (BFP) in oral reconstruction, 25 years after its first use as a pedicled flap.
      MATERIALS AND METHODS: A computerized literature search was conducted for
      articles published from 1977-2002. Mesh phrases used in the search were: buccal
      fat pad, buccal fat pad and oral reconstruction. RESULTS: A total of 43 articles
      were selected for the review based on the criteria for the study. Thirty of these
      articles were clinical articles, 8 were anatomic studies, 2 were review articles,
      1 was an experimental study and 2 discussion articles. Only 9 clinical articles
      were published prior to 1990, and between 1990 and 2002, a total of 21 clinical
      articles were published. Various application of BFP in oral reconstruction
      include closure of surgical defects following tumor excision, repair of surgical
      defects following excision of leukoplakia and submucous fibrosis, closure of
      primary and secondary palatal clefts, coverage of maxillary and mandibular bone
      grafts and lining of sinus surface of maxillary sinus bone graft in sinus lift
      procedure for maxillary augmentation. CONCLUSIONS: The easy mobilisation of the
      BFP and its excellent blood supply and minimal donor site morbidity makes it an
      ideal flap. The main advantages of BFP are ease of harvesting, simplicity,
      versatility, low rate of complications as well as quick surgical technique. The
      operation can be performed in one incision, affecting neither appearance nor
      function of the area.

PMID- 15505654
TI  - Experience in oesophageal substitution in Lagos, Nigeria.
AB  - This is an audit of five years work (1996 - 2001), in oesophageal substitution at
      the Cardiothoracic Surgery Unit of Lagos University Teaching Hospital, Nigeria.
      The study aimed at highlighting the current trends in indication and methods of
      oesophageal substitution in the context of our experience. We did a retrospective
      study of all who required oesophageal substitution during the period of study. We
      studied the various aspects of the patients' care including the indications for
      oesophageal substitution, the substituting organs and the results of surgery. We
      saw fifty-nine patients comprising 19 patients oesophageal carcinoma, 31
      corrosive strictures of the oesophagus, 4 peptic strictures and 3 achalasia
      cases. Two patients had oesophageal substitution because of mediastinitis. Fifty
      five patients underwent oesophageal substitution. The substituting organs were
      stomachs in 36 patients and colon in 19 patients. There were three anastomotic
      strictures, two grafts failed, and five cases of anastomotic leaks. In all,
      operative mortality was 9.1% . We concluded that oesophageal substitution was
      done more for benign reasons in our centre. We also emphasised the positive
      aspects of colon interposition and the prospects of doing more of it in the near
      future.

PMID- 15505655
TI  - Anal complaints in Nigerians attending Olabisi Onabanjo University Teaching
      Hospital (OOUTH), Sagamu.
AB  - The objective of this study was to determine prospectively the prevalence of anal
      complaints amongst Nigerians attending the General Out-patient Department (GOPD)
      of the hospital and review the records of those admitted to the surgical service
      with related complications. All the 272 patients attending the GOPD of OOUTH in
      November, 1999 were interviewed using a structured questionnaire. Information
      concerning age, sex, educational status, present or past history of at least one
      of the following symptoms viz recurrent bleeding per rectum, anal prolapse,
      anal/perianal pain, pruritus ani and anal discharge were obtained. Also obtained
      were reason(s) for current hospital attendance and any previous medical
      consultation. Those with at least one of the symptoms were classified as
      symptomatic. The symptomatic group had rectal examination including proctoscopy.
      The results showed that 82/272 (30.15% ) were symptomatic. Rectal examination on
      these 82 patients showed that 10(3.7% of 272) had haemorrhoids, 2(0.7% ) had
      rectal prolapse, 0.7% had peri-anal warts; 15(5.5% ) anal tags, 10(3.7% ) chronic
      anal fissure, 2 (0.7% ) perianal fistulae. In 29(10.4% ), the examination was
      normal and in 12 the rectum was too loaded with feaces to permit proctoscopy.
      However, only 5/272 (1.84% ) attended the clinic for the anal complaint, while
      12(4.4% ) had previously consulted a physician for same. Fear of impotence
      following surgery in 24 males and belief in herbal remedies in 32 patients were
      the main reasons for not consulting a physician. During the year 1999, out of a
      total of 558 admissions into our surgical service, only 4(0.6% ) were for
      complications related to anal complaints. This study indicated the prevalence of
      anal complaints in the study population of Nigerians as 30.15% , haemorrhoids
      constitute 3.7% and anal fissure 3.7% , contrary to low rates reported for
      developing countries. While this result cannot be extended to represent
      prevalence amongst Nigerians, it may be a pointer to what is to be expected.

PMID- 15505656
TI  - Halitosis (Fetor oris) in patients seen at the periodontology clinic of the
      University College Hospital, Ibadan - a subjective evaluation.
AB  - The aim of this study was to assess the prevalence of halitosis among periodontal
      patients and to evaluate the association between this condition and increasing
      age, social class, gender and oral hygiene status. The subjects comprised two
      hundred and fifty five consecutive patients who attended the periodontology
      clinic of the University College Hospital from November 1996 and March 1997. The
      patients were matched for sex and their ages ranged from 16 years to 74 years and
      made up of 128 males and 127 females. Cases of halitosis were cross-validated by
      two examiners to rule out a biased diagnosis. One hundred and twenty eight
      patients were males while 127 were females. A total of 37 patients presented with
      halitosis representing 14.5% . There was no statistically significant difference
      in relation to gender, p > 0.05. In the different age groups, only 7% of the
      subjects in the 31 - 40 years age group had halitosis while 36% of the subjects
      in the over 60 years age group were affected, (chi(2) - 13.01, df = 5, p < 0.05).
      There was also a statistically significant difference in the prevalence of
      halitosis according to oral hygiene status and social class. The results showed a
      low prevalence of halitosis as erroneously claimed but showed an association
      between the condition and increasing age, social class and oral hygiene status.

PMID- 15505657
TI  - Five years of Cancer Registration at Zaria (1992 - 1996).
AB  - From January 1992 to December 1996, a total number of 1887 new cancer cases were
      registered at the hospital-based cancer registry (CR) of Ahmadu Bello University
      Teaching Hospital (ABUTH), Zaria. There were 878 (46.6% ) males and 1008 (53.4% )
      females with male to female ratio M:F 1:1.12. Malignant lymphoma, 198 (22.5% )
      was the commonest cancer in men. This was followed by carcinoma of the urinary
      bladder, 103 (11.7% ) and prostate, 81 (9.2% ). In women cancer of the cervix,
      256 (25.35), breast 223 (22.1% ) and malignant lymphoma, 72 (3.1% ) were the
      commonest in that order. All the four new cases of cancer of the lung occurred in
      men. Brain tumour is rare and occurred during childhood. Data were collected from
      various sources within the hospital complex through active reporting.
      International classification of disease (ICD) 9th edition by WHO was utilised in
      the classification of primary sites of cancer. Cancer, a non-communicable disease
      is increasingly becoming a major public health concern, hence the need for a
      national policy formulation for its management and control.

PMID- 15505658
TI  - Radiographic and anatomic locations of mental foramen in northern Nigerian
      adults.
AB  - This study was undertaken to provide information on the most probable positions
      of the mental foramen among northern Nigerian adults. 157 panoramic radiographs
      randomly selected from patient's records at the Department of Dental Surgery,
      University of Maiduguri Teaching Hospital and 32 unsexed mandibles from the
      collection of bones in the Department of Human Anatomy, University of Maiduguri,
      were examined for the location of the mental foramen. The most common location
      was the interdental space between the first and second mandibular premolars
      (radiographs=34% , dry mandibles=32.8% ), closely followed by the position apical
      to the second premolars (radiographs=25.5% , dry mandibles=35.9% ). No
      significant difference in the distribution between males and females and the
      quantitative position was found to be bilaterally symmetrical in most cases.
      There is almost an equal chance of locating the mental foramen between the
      mandibular premolars and apical to the mandibular second premolar. This is of
      clinical importance with regards to the achievement of effective mental nerve
      block anaesthesia and the prevention of injury to the mental nerve during
      surgical procedures.

PMID- 15505659
TI  - Melorheostosis of Leri: report of a case in a young African.
AB  - Melorheostosis of Leri is a non-familial condition of hyperostosis of the
      cortical bone that usually presents unilaterally in long bones of the upper and
      lower limbs, but may also present in vertebra, ribs, skull and jaw. The incidence
      of this disease is quite rare, only about 300 cases have been reported worldwide.
      We present a case, which may be the first documented case in sub-Saharan Africa.
      CLINICAL PRESENTATION: S.K. is a 14 year old male student who presented to the
      hospital with an 18 month history of persistent pain in the joints of the right
      upper limb and a limb length discrepancy since birth which has worsened with
      growth. Examination revealed generalised hypoplasia of the right upper limb with
      shortening of the limb and atrophy of the muscles, also hypoplasia and
      contracture of the thumb was observed. The radiographs of the limb showed
      multiple areas of dense hyperostosis and scleroderma, which showed a linear
      distribution along the radial half of the bones. CONCLUSION: In children
      presentation of melorheostosis, is more likely be as limb length discrepancy,
      deformity or joint contractures which may be seen before radiographic evidence of
      any bony changes. Improvement in imaging techniques will therefore result in
      early diagnosis and greater success with conservative management. Also the
      increased frequency of tumours necessitates long-term follow up. KEYWORDS:
      melorheostosis, scleroderma.

PMID- 15505660
TI  - Life events, stress appraisals, and hospital doctors' mental health.
AB  - AIMS: To investigate psychological distress among Auckland Health Board hospital
      doctors, and to evaluate the unique relationships of idealism, stressful life
      events, and stress appraisals to their mental health. METHODS: A questionnaire
      consisting of the General Health Questionnaire (GHQ-12), the Physician Stress
      Inventory of stress appraisals, the Social Readjustment Rating Scale, and
      demographic questions was distributed to 680 Auckland Hospital doctors; 172
      (25.3%) of these doctors returned useable questionnaires. Psychological distress
      was defined by GHQ-12 global scores of current depression, anxiety, and
      psychiatric symptoms. RESULTS: Cases of psychological distress (29.1%) were
      comparable to those of GPs in New Zealand (NZ), Australia, and the United Kingdom
      (UK), and significantly higher than the general NZ population (although there
      were no demographic differences). Multivariate analysis of variance showed that,
      compared to non-cases, cases had higher mean stressful life-event scores and
      appraisal scores for internal professional stress, external professional stress,
      decreased work productivity, and interference with family life. Stepwise
      regression analysis revealed that life events and stress appraisals had a very
      large effect on psychological distress, with appraisals of decreased work
      productivity and interference with family life having significant effects.
      CONCLUSION: Stress appraisals need to be considered in examining the relationship
      between stressful situations and hospital doctors' mental health.

PMID- 15505661
TI  - Aligning medical education with the healthcare needs of the population.

PMID- 15505662
TI  - Empowerment and the employment relationship.

PMID- 15505663
TI  - Key issues facing Resident Medical Officers (RMOs).

PMID- 15505664
TI  - What evidence-based undergraduate interventions promote rural health?
AB  - AIMS: This article identifies published reports of medical undergraduate rural
      programmes from international medical schools and investigates the features
      making these programmes successful in recruiting and retaining rural physicians.
      METHOD: Literature review. RESULTS: Ten successful programmes were identified.
      Common features included selective admission, curricular focus on primary
      care/family medicine, community-based teaching, and community/rural
      preceptorship. A strong association exists between rural background of the
      student and choice of both a rural career and a career in primary care. Medical
      students of rural origin with an initial interest in a generalist career are
      significantly more likely to enter rural practice. Community preceptorship with
      its high staff:student ratio has been effective in influencing students' career
      choices. CONCLUSIONS: The effectiveness of a medical undergraduate rural
      programme in preparing and recruiting physicians for rural practice does not
      occur with one isolated strategy but with a chronological sequence of
      interventions. The most effective programmes consider both pre-medical school and
      medical school educational factors. Medical schools would need to implement a
      combination of these strategies when designing a programme to maximise success.

PMID- 15505665
TI  - Resident Medical Officer working conditions in New Zealand: results of a recent
      survey.
AB  - AIMS: To survey Resident Medical Officers (RMOs) and Senior Medical Officers
      (SMOs) working at Auckland District Health Board (ADHB) on various aspects of RMO
      working conditions and to trial the use of electronic keypad responders for this
      purpose. METHODS: In April 2004, the Physicians Grand Round at ADHB was used as a
      forum to conduct a survey on RMO working conditions in New Zealand. Results were
      collected anonymously using electronic keypad responders and recorded in a
      spreadsheet to allow analysis and comparison of the two professional groups.
      RESULTS: 27 RMOs and 32 SMOs attended and participated in the survey, answering
      11 questions. Responses showed significant differences between the two groups in
      7 of the 11 questions asked. In addition, both groups favoured changes to the
      status quo on a significant number of issues. CONCLUSIONS: RMOs and SMOs in New
      Zealand have differing opinions regarding the working conditions of RMOs. This
      study supports the need for wider scale, national discussion of these issues and
      the development of appropriate strategies to address these differences and their
      implications.

PMID- 15505666
TI  - Simulation-based training to improve acute care skills in medical undergraduates.
AB  - AIM: Acquisition of clinical skills by medical undergraduates can be problematic,
      especially in the context of medical emergencies. Simulation using computerised
      manikins may be an effective and ethical solution. We assessed the ability of
      undergraduates to manage medical emergencies, and evaluated simulation as an
      educational and assessment tool. METHOD: Medical undergraduates were assessed in
      standardised, highly contextualised simulations of medical emergencies using both
      checklists and global ratings, and were reassessed following a simulation-based
      educational intervention to measure learning effect. The scores for groups at
      different levels of training were compared to test construct validity of global
      ratings of simulator performance. We explored student perspectives of simulation
      through thematic analysis of questionnaire responses. RESULTS: Seventy-one
      students were studied. Final year students performed significantly better than
      fourth year students, but the ability to initiate management of medical
      emergencies was unsatisfactory in both groups. Performance improved significantly
      over the course of the simulation workshop. The learning processes in simulation
      based education were perceived as more effective than traditional methods, and
      consistent with known principles of effective learning. Students felt the
      simulations were a reasonable measure of their abilities and 91% felt that such
      simulations should be included in their end-of-year assessment. CONCLUSION:
      Current medical undergraduate training does not ensure new graduates can
      intervene effectively in an emergency. Simulation-based workshops are effective
      and should be incorporated into the undergraduate curriculum both for education
      and assessment of competence in emergency management.

PMID- 15505667
TI  - Analysis of the Advanced Choice of Employment (ACE) scheme for facilitation of
      first-year house officer appointments in New Zealand.
AB  - AIM: To determine the success of the Advanced Choice of Employment (ACE) scheme,
      a computerised matching system introduced to facilitate the recruitment of first
      year house officers in New Zealand. METHODS: ACE data was examined for
      demographics and employment outcomes in 2003 and 2004. Qualitative satisfaction
      was assessed via email survey of trainee intern applicants in 2003. RESULTS: All
      first-year house officer positions were filled within one round of matching. New
      Zealand trainee intern graduates were more successful than other applicant
      groups. The majority of successful applicants were employed by their most
      preferred hospital and 96% in one of their top four choices in both years.
      Tertiary centres were preferred over secondary centres. Survey demonstrated
      generally high satisfaction. CONCLUSIONS: The ACE scheme proved highly efficient
      and successfully accounted for applicant preferences. In addition, the emergence
      of centralised application data may improve workforce planning and increase
      retention of graduates.

PMID- 15505668
TI  - Administrators' perspectives of the challenges in recruiting and retaining
      psychiatrists for New Zealand: a national study.
AB  - OBJECTIVE: Administrators' perceptions of significant factors that might affect
      the recruitment and retention of psychiatrists for New Zealand's public mental
      health Services have not been previously investigated. METHODS: A postal
      questionnaire was sent to managers of all 21 of New Zealand's mental health
      Services. The questionnaire requesting information about any difficulties
      managers experienced in recruiting and retaining psychiatrists, factors they
      thought attract psychiatrists to join and stay, reasons why psychiatrists left,
      strategies they had tried to alleviate any psychiatrist shortages, and their
      relative success. RESULTS: Responses were received from 3 of 8 metropolitan
      Services and 8 of 13 non-metropolitan Services. Every service had experienced
      problems in recruiting and retaining psychiatrists over the past 5 years. New
      Zealand's general shortage of psychiatrists and limitations on recreational
      activities available in their area were reasons unanimously held to account for
      this. Factors unanimously identified as significant in influencing psychiatrists
      to join a mental health service were lifestyle, professional opportunities,
      functional multidisciplinary teams, and adequate staffing and training
      activities. Factors unanimously identified in retaining psychiatrists were levels
      of professional satisfaction, a reasonable on-call roster, functional
      multidisciplinary teams, adequate resources, and the ability to practise safely
      and within their area of expertise. There was no unanimity as to why
      psychiatrists would leave a service. Every service which attempted to assist
      psychiatrists with their relocation, and which found locums to cover so that they
      could take leave when they wanted, reported that these strategies had been wholly
      or partially successful in alleviating their psychiatrist shortage. CONCLUSIONS:
      Administrators' perspectives (which are often different to those of
      psychiatrists) about factors affecting recruitment and retention are worth
      investigating.

PMID- 15505669
TI  - Physician job satisfaction in New Zealand versus the United Kingdom.
AB  - AIMS: To compare and contrast levels of job satisfaction and job-related stress
      between doctors in New Zealand (NZ) and the United Kingdom (UK). METHODS: Self
      administered questionnaire to 593 NZ doctors and 795 UK doctors. Job satisfaction
      was scored using the Warr, Cook, and Wall scale. Job stress responses were
      correlated to satisfaction scores. RESULTS: Overall, job satisfaction levels were
      high; however, UK hospital physicians were found to be significantly less
      satisfied with their work than both NZ physicians and surgeons. Satisfaction with
      work was found to vary with working hours, amounts of paperwork, level of
      governmental interference, and time spent in public or private practice.
      CONCLUSION: Doctors in the UK face greater difficulty in gaining satisfaction
      from their work, as exemplified by the subgroup of UK physicians. This is due to
      a complex array of factors including conditions of the working environment and
      sociopolitical factors that are absent or minimal in New Zealand.

PMID- 15505670
TI  - Mentoring resident doctors.

PMID- 15505671
TI  - Workplace bullying: the silent epidemic.

PMID- 15505673
TI  - Unnecessary withdrawal of Vioxx.

PMID- 15505672
TI  - Allergic reactions to enoxaparin and heparin: a case report and review of the
      literature.

PMID- 15505674
TI  - Fear of the unknown: press coverage of bar owners' fears about smokefree bars.

PMID- 15505675
TI  - Medical image. Bleeding Meckel's diverticulum diagnosed with enterocolysis and
      mesenteric angiography.

PMID- 15505676
TI  - Recognising and responding to partner abuse: challenging the key facts.

PMID- 15505677
TI  - Cervical Cancer Inquiry.

PMID- 15505678
TI  - [Concordance in the treatment of schizophrenia].
AB  - Rates of medication nonadherence among outpatients with schizophrenia have been
      found to approach 50% during the first year after hospital discharge. Poor
      adherence with antipsychotic medications increases the risk of relapse.
      Nonadherent patients have an average risk of relapse that is 3.7 times greater
      than that of adherent patients. Studies results have demonstrated a rate of
      rejection to one year of 40% to 50%. These percentages are increased to 75% when
      the time is more than a year of the beginning treatment. Outpatients with
      schizophrenia who form strong alliances with their therapists seem to be more
      likely to comply with prescribed medications than patients who form weaker
      alliances. The significant progresses in the treatments with drugs can be
      possible, through improving the profile of adverse effects, search of alternative
      routes of administration and global improvement of the effectiveness of the
      medication. The additional support services as those proportionate ones for
      programs of treatment of the community, the family therapy, community services
      and the general help with strategies of compliance, they have a clear paper and
      they improve the results.

PMID- 15505679
TI  - [Eating behaviors, attitudes and obsessive-compulsive traits in adolescents of
      Buenos Aires City].
AB  - OBJECTIVE: Eating disorders are psychiatric illnesses of important prevalence in
      Argentina. Some typical characteristics of adolescence, such as body image
      fragility, media influence and social pressure lead partly into the development
      of eating disorders at that age. The objective of our study was to explore the
      eating behaviors, attitudes and obsessive-compulsive traits of the adolescents of
      Buenos Aires City. METHODS: A questionnaire survey was administered to 380
      students of 5 Buenos Aires high schools (mean age:16,8 years old) and their
      answers were analyzed. RESULTS: Almost 50% of the adolescents were not satisfied
      with their weight, 43% of them has been on a diet at least once (the majority
      because of aesthetic reasons). A percentage of 23,5 had bulimic behaviors, 34,5%
      had a high number of obsessive-compulsive traits. Women were significantly more
      dissatisfied with their weight, had been on more diets and had more bulimic
      behaviors and obsessive-compulsive traits. CONCLUSIONS: Weight dissatisfaction
      and bulimic behaviors are frequent in adolescents of Buenos Aires City, specially
      among women. Preventive measures against eating disorders should be done on this
      population.

PMID- 15505680
TI  - [Neurobiology of depression and stress syndromes. Focus on active neurosteroids
      and neurosteroids].
AB  - That the brain is a target for hormones is a well established fact. Today we also
      know that brains can secrete the whole gamut of peptides and steroid hormones,
      i.e., pregnanes and pregnenes. Considering that the ancestral neuron was a
      neurosecreting cell, this is not surprising. As CRH and cortisol secretion occur
      in situ in nervous systems, the intriguing possibility that anxio-depressive
      syndromes may be associated with paracrine effects of these compounds on the
      brain should now be considered. The concept of stress as a specific reaction of
      the nueroendocrine system to nocuous stimuli is re-examined in light of new
      evidence. The fundamental importance of historical, social, and psychological
      contexts in evaluating hormonal actions is emphasized. Problems emerging from the
      attempt to search for specific biological markers in different psychiatric
      disorders are discussed. The suggestion is made that, rather than to categorize
      nosological entities, biological dysfunctions should be elated with psychological
      abnormalities.

PMID- 15505681
TI  - [Treating depression? All secrets exposed! The tricks of the trade!].
AB  - Depression is highly prevalent in the general population and is also costly to
      society. Although a wide range of pharmacological and psychological
      antidepressant therapies is available, the vast majority of people with
      depression remain unrecognised and untreated. Most depressed patients will
      respond to appropriate treatment, but the clinical management of depression
      involves far more than antidepressant drugs alone. Treatment failure, or
      refractory depression, can be overcome when therapeutic strategies adopt a
      logical, comprehensive and long-term approach. Understanding the interplay of
      clinical and neurochemical factors associated with the pathogenesis of depression
      can help physicians to find effective therapeutic alternatives for most of the
      depressed patients under their care.

PMID- 15505683
TI  - [Stress and cognitivism].
AB  - In this article, a brief account of the psychological sense of stress is
      referred. Richard Lazarus' transaccional theory is described in detail; his first
      transaccional cognitive theory and his last cognitive-emotional transaccional
      theory. Stress is also described from other points of view, such as Grenberg's
      emotional theory. The new construct Psychofortology is defined and some
      references about the principal authors are made. Psychotherapeutic possibilities
      from the different psychological schools mentioned are described.

PMID- 15505682
TI  - [Depression and anxiety: from clinic to pharmacological treatment].
AB  - Either as a symptom or as a trait of an axis I disorder, anxiety is frequently
      associated with depressive episodes. Its treatment depends mainly of the syndrome
      in which it is included. While the selective serotonin reuptake inhibitors seem
      to be indicated in depression with comorbid anxiety disorders and in anxious
      depression, in agitated depression may be preferable to indicate mood stabilizers
      or sedative antipsychotics. Benzodiazepines may be useful at the beginning of the
      treatment of these special forms of depression, but it is advisable to tapper
      them off once the affective and/or the anxiety disorders improve.

PMID- 15505684
TI  - [Clinical management of patients with depression and cardiac disease].
AB  - Depression occurs in 15 % to 20 % of patients with acute coronary syndromes and
      it is also and independent risk factor for morbidity and mortality. Treatment
      with selective serotonin reuptake inhibitors is effective, safe and may improve
      survival after myocardial infarction in patients with depression.

PMID- 15505685
TI  - [Anxiety, nostalgia and melancholy. A few remarks on psychoanalysis and tango].
AB  - Our work is based on the application of psychoanalytic techniques, in order to
      unveil this cultural phenomenon called tango, related with sexuality and
      unconscious processes. As a way of introduction, it deals with a brief theory of
      the birth of tango, the possible terminological source of its name, its main
      creators and interpreters, as well as the chronological classification into the
      first wave tangos, Guardia Vieja, and the newer wave tangos, Guardia Nueva. The
      former ones were awash with festive themes of the centennial years, expressed in
      behaviors that denote sexuality and love, whereas the latter ones, expose the
      great bewilderment of the thirties' crisis, due to the imminent downfall of the
      country, the denunciation of materialism, the crumbling of ideas; which led up to
      feelings of utter pessimism, loneliness and abandonment. From this point onwards,
      through the use of techniques provided by psychoanalysis applied to tango lyrics,
      we are able to unravel the unconscious processes of the drama of its characters;
      the immigrant, hopeful and at same time nostalgic for the loss of his mother
      country; the porteno -urban man from Buenos Aires city- who, overwhelmed by
      immigrants, has to give way to the new compatriots; the inland inhabitant, who
      was dragged to the city because of the new conditions of rural work; and finally
      the conventillo, tenement house, as a melting pot that fulfilled the integration
      of these groups. Like in a painter's palette, which contains various colors and
      shades, the interpretations about nostalgia, grief and loneliness become
      apparent, along with the father-son rivalry, the conflict with the absent mother,
      the relationship between sexes, male chauvinism, infatuation, identity, the fear
      of death, the rebirth to a new life, the passage from gaucho to guapo, from a
      shrewd horseman to a daring, bullying braggart.

PMID- 15505686
TI  - [Paroxysmal anxiety].

PMID- 15505687
TI  - [The contribution of psychoanalysis to medicine].

PMID- 15505688
TI  - [New molecular targets in pharmacological treatment of anxiety disorders].
AB  - Benzodiazepines are effective and widely used in anxiety disorders, but they
      produce sedation and dependency. Molecular studies have shown that binding
      benzodiazepines to GABAA receptors containing the Alpha1 subunit mediates the
      sedative properties of benzodiazepines. Other strategies are being developed
      including the use of the selective GABA reuptake inhibitor tiagabine and the
      voltage gated calcium ion channel ligand pregabalin. Several novel strategies are
      being developed based on preclinical observations, including corticotrophin
      releasing factor (CRF) antagonists, substance P antagonists, and drugs inhibiting
      glutamate neurotransmission.

PMID- 15505689
TI  - [The validity of Freud's concepts of neurosis in present diagnosis systems].
AB  - Anxiety as a symptom, syndrome and diagnosis is discussed, as well as its
      overlapping with the concept of neuroses. The original concepts of neuroses,
      neurasthenia and psychasthenia that have been coined since the eighteenth century
      are revised, as well as its evolution from Freud to DSM IV and ICD 10.

PMID- 15505690
TI  - [Anxiety and alcoholism].
AB  - Anxiety as a symptom is very frequent in alcoholic patients and the comorbidity
      between alcoholism and anxiety disorders is very high. One of the reasons is the
      reciprocal implication between both pathologies. Habitually, it is better to
      treat both disorders at the same time, specially panic disorder and posttraumatic
      stress disorder. We must be cautious with the use of benzodiazepines. Generally
      we must prefer SSRI and other drugs.

PMID- 15505691
TI  - [Stress, anxiety and cardiovascular disease: an interdisciplinary approach].
AB  - Many clinic investigations support the relation between coronary heart disease
      (CAD) and psychosocial factors (PFs) and how these two entities influence each
      other. On one hand, FPs like depression, anxiety, social isolation, stress and
      some types of personality, contribute significantly to the pathogenesis and
      expression of CAD. Pathophysiological mechanisms underly in this interrelation,
      can be divided between FPs conditions that contribute to a higher frequency of
      adverse health behaviors (eg. smoking) or directly increasing the platelets and
      neuroendocrine activity. In this review there is information relating CAD to
      acute stress and individual differences in sympathetic nervous system
      responsivity. New technologies and research demonstrate that acute stress
      triggers myocardial ischemia, promotes arrhythmogenesis, stimulates platelet
      function, and increases blood viscosity through hemoconcentration. Recent data
      also indicate that the foregoing effects are in part a result of the endothelial
      dysfunction and injury induced by acute stress. The complex interactions among
      vascular endothelium, platelets, serotonin and blood components are one of the
      most exciting research areas today. The importance of maximizing the efficacy of
      psychological and psychopharmacology interventions is in part because of the
      knowledge that psychosocial stresses tend to cluster together and when this takes
      place, the resultant risk for cardiac events is often substantially elevated,
      equaling that associated with previously established risk factors for CAD, such
      as hypertension and hypercholesterolemia. Thus, to know about these mechanisms,
      helps to widen the view and use therapeutic strategies that go beyond symptomatic
      effects and commit us to an interdisciplinary work.

PMID- 15505692
TI  - [Sleep disorders and panic attacks].
AB  - The aim of this work is to describe the clinical and polisomnographical
      characteristics of patients suffering prevailing night panic attacks. The most
      usual therapeutics are also briefly mentioned. The Polisomnography and especially
      the EGG are mentioned as the methods which allow the most accurate diagnosis
      since the night panic attack produces patognomonical disturbances.

PMID- 15505693
TI  - [Psychotherapy or psychopharmacology? Eight criteria to think the problem].
AB  - Psychotherapy and psychopharmacology are two resources we can put into use in
      treatment; they are, as well, two viewpoints from which we look at the patient's
      problems. Although the association has become popular, clinicians don't find in
      the literature clear criteria to decide, in many cases, whether it is more useful
      to implement one or the other, or both. This presentation provides orientation
      guidelines, based on a more comprehensive publication.

PMID- 15505694
TI  - [Psychotropic drugs: cure or resource?].
AB  - This work summarizes the difficulties and aims of psychotropic administration in
      the treatment of mental disorders. The results of a survey about attitudes of
      psychoanalysts of the main psychoanalytic institutions in Argentina towards
      indications and objectives of psychotropic drugs use in psychoanalytic patients
      are summarized. Neurosciences attempts to build a bridge to connect biological
      and psychological and psychoanalytic knowledge, but for this efforts to be
      fruitful the non-dogmatic participation of professionals from the mind sciences
      may be necessary.

PMID- 15505695
TI  - [Importance of interleukin 2 soluble receptors determination in patients over 60
      years with untreated depression].
AB  - Even though over more than 20 years researchers link different moods and immune
      function, since 1995 biologic and biochemical research on immune disfunction
      characterization have been published. Advances in this clinical research will
      broaden current knowledge on depressive moods. The Interleukin-2 soluble
      receptors determination (Il2sr) is a feasible assay which do not require too much
      laboratory complexity.

PMID- 15505696
TI  - [Use of benzodiazepine in the Neuropsychiatric Hospital of Cordoba Province].
AB  - From their introduction in the psychiatric clinic, benzodiazepines have meant a
      great advance in the treatment of numerous pathologies, due to their therapeutic
      effectiveness and safety. Despite the consensus that indicates the rational use
      of this medication, it is much too frequently that actual practice does not
      conform with said criteria. We believed it necessary to conduct a revision
      regarding the prescription of benzodiazepines in our institution. For that
      purpose, we carried out a retrospective study using 130 medical histories trough
      a three-year period, analyzing the indication and duration of benzodiazepine
      usage. Consequently, we are able to affirm that the use of benzodiazepine, in
      relation to diagnosis and duration of usage, is not made according to
      international guidelines.

PMID- 15505697
TI  - Questionnaires.

PMID- 15505698
TI  - After guidelines, what?

PMID- 15505699
TI  - Smoking in health science students with asthma.
AB  - It is expected that asthmatic students in a health science department would avoid
      the hazards of cigarette smoking due to the knowledge they gain through their
      studies. Surprisingly, health science students with asthma had a higher
      prevalence of smoking than their healthy colleagues.

PMID- 15505700
TI  - Does technetium-99m diethylenetriaminepentaacetate clearance predict the clinical
      course of idiopathic pulmonary fibrosis?
AB  - Clearance of inhaled technetium-99m diethylenetriaminepentaacetate (99mTc-DTPA)
      is a potential indicator of disease activity and progression in idiopathic
      pulmonary fibrosis (IPF). The objective of the present study was to evaluate the
      prognostic value of 99mTc-DTPA scans in IPF. A total of 22 patients (18 males),
      aged 33 to 80 years with IPF were followed for six to 20 months (mean 13 months).
      At diagnosis, high resolution computed tomography (HRCT) scans showed a honeycomb
      pattern with bibasilar reticular opacities in all cases. At T0 (diagnosis) and T1
      (follow-up), each patient had pulmonary function tests (forced vital capacity,
      diffusing capacity of the lung for carbon monoxide and partial arterial O2
      pressure), extension of fibrosis evaluated by HRCT visual score and 99mTc-DTPA
      lung clearance. Results at T0 and T1 were compared, taking into account the whole
      population and patients with relatively fast and slow 99mTc-DTPA wash-out. 99mTc
      DTPA clearance did not show any significant correlation with functional tests or
      HRCT score. These findings indicate that clearance of inhaled 99mTc-DTPA is not
      of value in following the progress of IPF.

PMID- 15505701
TI  - French-Canadian version of the Chronic Respiratory and St George's Respiratory
      questionnaires: an assessment of their psychometric properties in patients with
      chronic obstructive pulmonary disease.
AB  - BACKGROUND: French versions of the Chronic Respiratory Questionnaire (CRQ) and
      the St George's Respiratory Questionnaire (SGRQ) have largely been used in
      Canada, although the process by which they were translated remains unknown and
      the psychometric properties of these translated versions have not been assessed
      in a properly designed study. OBJECTIVE: To translate and evaluate the
      psychometric properties of the French-Canadian versions of the CRQ and the SGRQ.
      METHODS: The questionnaires were translated according to standardized guidelines
      for cross-cultural adaptation. Measurements were made at baseline and again after
      two weeks in 27 chronic obstructive pulmonary disease (COPD) patients known to
      have stable disease. Measurements were also taken pre- and post-treatment in
      patients with acute exacerbation of COPD (33 patients) or in pulmonary
      rehabilitation (32 patients). RESULTS: The CRQ showed high test-retest
      reliability (the majority above 0.70), although it was slightly lower for the
      dyspnea dimension (0.58 to 0.65). The SGRQ also showed high test-retest
      reliability (above 0.80), although it was lower for the symptoms dimension (0.54
      to 0.58). The internal consistency reliability coefficients ranged from 0.73 to
      0.90 for the CRQ and above 0.80 for the SGRQ, except for the symptoms dimension.
      The Pearson's correlation coefficients were low (less than 0.30) between most of
      the translated questionnaire dimension scores and forced expiratory volume in 1
      s, 6 min walking test and dyspnea measures. The correlation was generally high
      (greater than 0.50) between the two questionnaires and the 36-item short form
      health survey, and for those domains that measured the same construct. The
      changes in the total and subscale scores of the CRQ and the SGRQ (except for the
      symptoms domain) were all largely above the variability of the score in the
      stable disease group. CONCLUSION: The present study confirms that the French
      Canadian translated versions of the CRQ and the SGRQ perform well with respect to
      their psychometric properties. They are both suitable for their intended purpose,
      ie, to detect change in health status in patients with COPD when assessing if a
      treatment is beneficial. However, the symptoms domain of the SGRQ cannot be used
      to assess acute change with respect to a given therapy.

PMID- 15505702
TI  - Canadian Standards Association standard CAN/CSA/Z264.1-02:2002: a new voluntary
      standard for spacers and holding chambers used with pressurized metered-dose
      inhalers.
AB  - A new Canadian standard (CAN/CSA/Z264.1-02:2002) has been published with the
      purpose of helping to ensure the safety, efficacy and functionality of spacers
      and/or holding chambers. They are prescribed for use by spontaneously breathing
      patients for the treatment of various respiratory diseases where medication is
      delivered to the lungs using pressurized-metered dose inhalers. This consensus
      standard was developed with the support of pharmaceutical companies and
      manufacturers of spacers and holding chambers, and with the help of clinicians,
      retail pharmacists and representatives of patient advocate bodies associated with
      respiratory diseases and the dissemination of information related to the
      treatment and the delivery of inhaled medications. Advice was also sought from
      expert groups outside of Canada to ensure that the standard would be relevant
      internationally. Whereas monographs in the pharmaceutical compendia and guidance
      documents published by regulatory bodies provide information that is largely
      about the drug product and inhaler, this is the only standard whose focus is
      primarily on these add-on devices. The purpose of the present review is to
      highlight the main features of the standard for clinicians by describing its
      scope, the tests that are intended to assure the robustness of the construction
      of these devices, the type of testing that is specified to establish in vitro
      efficacy, and the recommendations for the marking and labelling of the device and
      its associated packaging. Manufacturers who test their products to this Canadian
      Standards Association standard will be able to provide performance information
      about add-on devices to the clinician, facilitating an informed decision when
      selecting devices for patients.

PMID- 15505703
TI  - Effects of pleural effusion on respiratory function.
AB  - The accumulation of pleural effusion has important effects on respiratory system
      function. It changes the elastic equilibrium volumes of the lung and chest wall,
      resulting in a restrictive ventilatory effect, chest wall expansion and reduced
      efficiency of the inspiratory muscles. The magnitude of these alterations depends
      on the pleural fluid volume and the underlying disease of the respiratory system.
      The decrease in lung volume is associated with hypoxemia mainly due to an
      increase in right to left shunt. The drainage of pleural fluid results in an
      increase in lung volume that is considerably less than the amount of aspirated
      fluid, while hypoxemia is not readily reversible upon fluid aspiration.

PMID- 15505704
TI  - A case of primary lung cancer producing alpha-fetoprotein.
AB  - A case of lung carcinoid showing elevated plasma alpha-fetoprotein (AFP) level is
      reported. A 44-year-old man who complained of the development of bloody sputum
      had a left hilar lung mass on chest radiograph. The serum level of AFP was
      markedly increased to 8438 ng/mL. After resection, it was diagnosed as an
      atypical carcinoid, and the tumour cells were positive for cytoplasmic AFP. AFP
      is one of the most useful tumour markers for the diagnosis of hepatic cell
      carcinoma or germ cell tumours. It has also been reported that some primary lung
      tumours produce AFP. However, these tumours are mainly poorly differentiated
      adenocarcinomas or large cell carcinomas. A lung carcinoid that produces AFP is
      extremely rare.

PMID- 15505706
TI  - A novel pyrrole synthesis.
AB  - The silver(I)-promoted oxidative cyclization of homopropargylamines at room
      temperature provides a novel access to pyrroles. Homopropargylamines are readily
      available by the addition of a propargyl Grignard reagent to Schiff bases.

PMID- 15505705
TI  - The ins and outs of molecular encapsulation.
AB  - Molecular capsules can act as hosts for appropriate guests, and bring them into
      well-defined nanoenvironments. Various spectroscopic methods have been used to
      deduce the mechanism of guest exchange in such systems. Generally, the guests get
      in and out of capsules through the opening and closing of host "flaps" but
      smaller capsules can exchange simply by dissociation of the host subunits.

PMID- 15505707
TI  - Synthesis of 11C-labelled N,N'-diphenylurea and ethyl phenylcarbamate by a
      rhodium-promoted carbonylation via [11C]isocyanatobenzene using phenyl azide and
      [11C]carbon monoxide.
AB  - The reaction with phenyl azide and [11C]carbon monoxide to give N,N'
      diphenyl[11C]urea and ethyl phenyl[11C]carbamate has been studied with the aim of
      development of a new methodology for carbonylation using [11C]carbon monoxide
      with high specific radioactivity. The synthesis of 11C-labelled N,N'-diphenylurea
      from phenyl azide and [11C]carbon monoxide, with 1,2-bis(diphenylphosphino)ethane
      bound Rh(I) complex at 120 degrees C at a pressure of 35 MPa in the presence of
      aniline was accomplished in 82% trapping efficiency and 82% conversion yield.
      This approach was also useful for the synthesis of ethyl phenyl[11C]carbamate
      with lithium ethoxide as a nucleophilic reagent giving 90% trapping efficiency
      and 76% conversion yield. These reactions can be considered to proceed via a
      [11C]isocyanate or a [11C]isocyanate-coordinated Rh complex to give the
      corresponding 11C-products. This protocol provides the chemical basis for the
      synthesis of [11C]urea and [11C]carbamate derived from [11C]isocyanates.

PMID- 15505708
TI  - Experimental data checker: better information for organic chemists.
AB  - An experimental data checker has been developed that reads, analyses, and cross
      correlates experimental information copied and pasted from authors' manuscripts,
      which will be useful for authors, referees, editors and readers of papers
      reporting new molecular information, and which makes possible a quantification of
      the accuracy of journals' data.

PMID- 15505709
TI  - Probing the effect of the amidinium group and the phenyl ring on the
      thermodynamics of binding of benzamidinium chloride to trypsin.
AB  - The effect of the amidinium group and the phenyl ring on the thermodynamics of
      binding of benzamidinium chloride to the serine proteinase trypsin has been
      studied using isothermal titration calorimetry. Binding studies with
      benzylammonium chloride, [small alpha]-methylbenzylammonium chloride and
      benzamide, compounds structurally related to benzamidinium chloride, showed that
      hydrogen bonding between the amidinium group and the enzyme is primarily enthalpy
      driven. Binding of cyclohexylcarboxamidinium chloride and acetamidinium chloride
      showed that the hydrophobic binding of the phenyl ring in the S1 pocket is
      primarily entropy-driven and that a rigid, flat hydrophobic binding site for the
      inhibitor is favourable. The compounds that have been studied over a range of
      temperatures exhibit a negative change in heat capacity upon binding and enthalpy
      entropy compensation, both characteristic of hydrophobic interactions.

PMID- 15505710
TI  - EPR and affinity studies of mannose-TEMPO functionalized PAMAM dendrimers.
AB  - Mannose-TEMPO functionalized G4-PAMAM dendrimers with increasing mannose loadings
      have been synthesized and characterized by MALDI-TOF MS and EPR spectroscopy.
      Analysis of linebroadening effects in the EPR spectra of these dendrimers allowed
      us to determine the relative presentation of mannose and TEMPO on the dendrimer
      surface. Hemagglutination assays and affinity chromatography/EPR experiments to
      assess the activity of the mannose-TEMPO dendrimers with Concanavalin A are
      presented.

PMID- 15505711
TI  - Preferred dimerization of tetra-tolyl- and tetra-tosylurea derivatives of
      flexible and rigidified calix[4]arenes.
AB  - The dimerization of tetratolyl- and tetratosyl-urea derivatives 1 and 2, derived
      from a tetrapentoxy calix[4]arene in the cone conformation and of the
      corresponding tetra-urea derivatives 3 and 4, in which the cone conformation is
      rigidified by the two crown-3 tethers, have been studied. All six possible
      equimolar mixtures were examined by 1H NMR using CDCl3 and CD2Cl2 as solvents.
      While no heterodimers are found for the combinations 1/3 and 2/4 in either
      solvent, all remaining combinations lead to the (exclusive) formation of
      heterodimers in CD2Cl2. In CDCl3 heterodimers are only observed for the
      combinations of 3 with 2 or 4. These results are discussed in terms of entropic
      and enthalpic contributions and compared with MD-simulations in a box of
      chloroform solvent molecules.

PMID- 15505712
TI  - Spirobicyclo[2.2.2]octane derivatives: mimetics of baccatin III and paclitaxel
      (Taxol).
AB  - The formylated spirobyclic alcohol was computer modeled to be a mimetic of
      paclitaxel. In this model, the formyl group was used as a truncated paclitaxel
      side chain in order to reduce the computational work. Compound , carrying the
      paclitaxel side chain, was synthesized in six steps from optically active 1,3
      diketone . Microtubule stabilization was not observed for , indicating that the
      model needs to be adjusted.

PMID- 15505714
TI  - Palladium-catalysed cascade ring expansion reaction of cyclobutanols that have a
      propargylic moiety with nucleophiles.
AB  - Cascade ring rearrangement of four-membered ring systems containing various
      propargylic components by a palladium catalyst is described. The reactions of
      cyclobutanols that have a propargylic carbonate moiety with phenols as
      nucleophiles produce phenoxy-induced cyclopentanones in high yields. The
      reactions proceed in a regio- and diastereoselective manner to afford the
      substituted cyclopentanones with high selectivities. Imides also act as
      nucleophiles to produce the imidyl-induced products. Propargylic bromide
      successfully reacts with sodium alkoxides to produce the corresponding products
      in good yields.

PMID- 15505713
TI  - Schizophyllans carrying oligosaccharide appendages as potential candidates for
      cell-targeted antisense carrier.
AB  - Schizophyllans carrying beta-lactoside and alpha-mannoside appendages were
      prepared from native schizophyllan through NaIO4 oxidation followed by reductive
      amination using aminoethyl-beta-lactoside and alpha-mannoside, respectively. The
      resulting schizophyllans form stable macromolecular complexes with
      polynucleotides, such as poly(C) and poly(dA). Specific affinity between these
      macromolecular complexes and saccharide-binding proteins was demonstrated by
      surface plasmon resonance and agarose gel staining assays. beta-lactoside
      appended schizophyllan enhanced an antisense activity in hepatocytes which
      express lactoside-binding proteins on their cell surfaces.

PMID- 15505715
TI  - Synthesis of protoheme IX derivatives with a covalently linked proximal base and
      their human serum albumin hybrids as artificial hemoprotein.
AB  - The simple one-pot reaction of protoporphyrin IX and omega-(N
      imidazolyl)alkylamine or O-methyl-L-histidyl-glycine with benzotriazol-1-yl
      oxytris(dimethylamino)phosphonium hexafluorophosphate at room temperature
      produced a series of protoporphyrin IX species with a covalently linked proximal
      base at the propionate side-chain. The central iron was inserted by the general
      FeCl2 method, converting the free-base porphyrins to the corresponding protoheme
      IX derivatives. Mesoporphyrin IX and diacetyldeuteroporphyrin IX analogues were
      also prepared by the same procedure. The Fe(II) complexes formed dioxygen (O2)
      adducts in dimethylformamide at 25 degrees C. Some of them were incorporated into
      the hydrophobic domain of recombinant human serum albumin (rHSA), providing
      albumin-heme hybrids (rHSA-heme), which can bind and release O2 in aqueous media
      (pH 7.3, 25 degrees C). The oxidation process of converting the dioxygenated heme
      in rHSA to the inactive Fe(III) state obeyed first-order kinetics, indicating
      that the mu-oxo dimer formation was prevented by the immobilization of heme in
      the albumin scaffold. The rHSA-heme, in which the histidylglycil tail coordinates
      to the Fe(II) center, showed the most stable O2 adduct complexes.

PMID- 15505716
TI  - Arylethynylacridines: electrochemiluminescence and photophysical properties.
AB  - Electrogenerated chemiluminescence (ECL) of six new ethyne-based acridine
      derivatives (1-6) has been studied. The new acridine derivatives were synthesized
      by cross-coupling of 9-chloroacridine and corresponding donor-substituted
      phenylethynes under modified Sonogashira conditions. The donor groups were varied
      in the order of increasing steric hindrance and donor strength at the donor site.
      The solution phase photophysical properties and ECL of these compounds were
      studied comparatively in acetonitrile solvent. The UV-Visible spectra of
      compounds 1-5 exhibit closely the same maxima. Density functional theory (DFT)
      has been invoked to analyze and understand the unexpected UV-Visible absorption
      behavior. Compounds with weak electron donors produce excimer ECL irrespective of
      steric hindrance at the donor site, while the compound with a stronger donor
      gives rise to ECL that is blue-shifted with respect to its photoluminescence
      spectrum. All except one of these compounds also exhibit solid state fluorescence
      which may be useful for solid state devices such as organic light emitting diodes
      (OLEDs) and as laser dyes. The observed properties are discussed with reference
      to the structure of the compounds synthesized.

PMID- 15505718
TI  - Preparation of gamma-siloxyallyltributylstannanes and their use in the synthesis
      of (+/-)-1-deoxy-6,8a-di-epi-castanospermine.
AB  - gamma-siloxyallyltributylstannanes were selectively obtained as E or Z isomers
      from beta-tributylstannylacrolein upon reaction with lithium or magnesium
      alkylcyanocuprates. The ability of the reagents to give a high syn selectivity
      when added to iminium salts has been used for the efficient synthesis of (+/-)-1
      deoxy-6,8a-di-epi-castanospermine from succinimide. The key step of the synthesis
      was the allylstannation of the N-allyliminium intermediate followed by ring
      closing metathesis.

PMID- 15505717
TI  - Synthesis and antimicrobial activity of some netropsin analogues.
AB  - Nine novel lexitropsins were synthesized by linking two netropsin-like moieties
      through three different dicarboxylic acids; 9,10-dihydro-2,7
      phenanthrenedicarboxylic acid; [(3
      [[(carboxymethyl)amino]carbonyl]benzoyl)amino]acetic acid and indole-2,5
      dicarboxylic acid. The netropsin residues were modified by the use of N
      isopentylpyrrole, 5-methylthiophene or 5-isopropylthiazole heterocyclic building
      blocks in place of the usual N-methylpyrrole. The compounds were tested against
      five gram-positive bacteria: Staphylococcus aureus, Streptomyces faecalis,
      methicillin resistant Staphylococcus aureus, Enterobacter cloacae, Mycobacterium
      fortuitum, three gram-negative bacteria: Klebsiella aerogenes, Proteus vulgaris,
      Escherichia coli and three fungi: Aspergillus niger, Candida albicans and
      Aspergillus nidulans. Some of the compounds showed significant inhibitory effects
      on the growth of the microorganisms.

PMID- 15505719
TI  - A Lewis acid-promoted cyclization of ethenetricarboxylate derivative aromatic
      compounds. Novel syntheses of oxindoles and benzofuranones via Friedel-Crafts
      intramolecular Michael addition.
AB  - A novel cyclization reaction of ethenetricarboxylate derivative aromatic
      compounds in the presence of various Lewis acids gave benzo-annulated cyclic
      compounds such as oxindole and benzofuran derivatives via Friedel-Crafts
      intramolecular Michael addition in high yields. For example, the reaction of
      diethyl 2-[(N-methyl-N-phenylcarbamoyl)methylene]malonate (1a) in the presence of
      ZnCl2 at room temperature gave diethyl 2-(1-methyl-2-oxoindolin-3-yl)malonate
      (2a) in 98% yield. The reactions also proceeded with a catalytic amount of a
      Lewis acid such as AlCl3, ZnCl2, ZnBr2, Sc(OTf)3, or InBr3.

PMID- 15505720
TI  - Synthetic protocols, molecular polarity, and 13C NMR correlations for 1-aryl- and
      1-diarylmethylidene-1H-cyclopropa[b]naphthalenes.
AB  - The Peterson olefination for alkylidenecycloproparene synthesis from a 1,1
      disilylcycloproparene has been refined into five distinct protocols that have
      provided 43 new aryl- (5 and 6) and diaryl- (7 and 8), and aryl(phenyl)- (9 and
      10) methylidene derivatives. The permanent dipole moments of these and other
      previously reported compounds have been measured and the direction of the dipole,
      to or from the cycloproparenyl moiety, established for each compound. The 13C NMR
      spectra are fully assigned and linear correlations of carbon chemical shift with
      the Hammett sigmap+ constants for each atom within the cycloproparene moiety are
      provided for the 8-11 compounds that comprise each substitution pattern present
      in 5-10.

PMID- 15505721
TI  - Study of regioselective methanesulfonylation of simple aromatics with
      methanesulfonic anhydride in the presence of zeolite catalysts.
AB  - Regioselective methanesulfonylation of simple aromatics using methanesulfonic
      anhydride can be achieved over zeolite catalysts. For example,
      methanesulfonylation of toluene over various cation-exchanged zeolite beta
      catalysts affords higher para-selectivity in the synthesis of methyl tolyl
      sulfone than standard Friedel-Crafts methanesulfonylation utilising aluminium
      chloride.

PMID- 15505722
TI  - Facile photochemical synthesis of mixed siloxyacetal glycosides as potential pH
      sensitized prodrugs for selective treatment of solid tumors.
AB  - Photochemical reactions of a variety of acylsilanes with peracetylated free
      glycosides in anhydrous benzene at ambient temperature yielded novel, highly acid
      sensitive siloxyacetal glycosides in 75-90% yields with complete retention of
      configuration at the anomeric center. Subsequent deacetylation of
      triisopropylsiloxy- and tert-butyldimethylsiloxy derivatives with sodium
      methoxide in methanol afforded deprotected siloxyacetal glycosides in nearly
      quantitative yields. Acid hydrolysis of trimethylsilyl siloxyacetals proceeded
      with a half-life of 17.5 minutes at pH 6.2 which is vastly superior to the
      decomposition rate of conventional acetals under similar conditions. The
      structure of one of the novel siloxyacetals was confirmed by X-ray
      crystallography. In vitro biological studies showed that glucose-derived
      siloxyacetals may serve as potential pH-activated prodrugs for selective
      treatment of solid tumors.

PMID- 15505724
TI  - Lipase-mediated production of defensive toxins in the marine mollusc Oxynoe
      olivacea.
AB  - Metabolites related to caulerpenyne (1), a toxic sesquiterpene featured by two
      enol-acetate residues, play a major role in the chemical defence of both algae of
      the genus Caulerpa and a few molluscs of the order Sacoglossa. Here we report the
      direct evidence that cell-free preparations of Oxynoe olivacea, a Mediterranean
      sacoglossan, transform efficiently the algal metabolite 1 to oxytoxin-2 (3), the
      main defensive metabolite of the mollusc. The process implies two distinct
      hydrolytic activities, here named LIP-1 and LIP-2, able to operate either
      hydrolysis of the acetyl residue at C-1 or concerted elimination of the acetyl
      groups at C-4 and C-13. Incubation experiments with tissue homogenates of O.
      olivacea or with commercially available lipases suggest a two-step mechanism that
      involves, in vitro, an unstable metabolite characterized as preoxytoxin-2 (4).
      The course of the entire process can be easily monitored by reverse phase
      HPLC/ESI-MS, as well as by NMR measurements, which provides direct evidence of
      the enzymatic mechanism leading to the formation of this last compound (4). In
      agreement with the literature, both fresh and frozen tissues of Mediterranean
      Caulerpa prolifera also have the capability to transform 1 into aldehydic
      derivatives, namely oxytoxin-1 (2) and oxytoxin-2 (3), through hydrolysis of the
      acetyl groups. However, differently from experiments with mollusc homogenates,
      the conversion is not complete and caulerpenyne (1) can be detected in the algal
      suspension for a few hours. HPLC/ESI-MS monitoring of this transformation
      suggests that the hydrolytic route involves different activities in the mollusc
      and seaweed.

PMID- 15505723
TI  - Calix[4]arene methylenebisphosphonic acids as calf intestine alkaline phosphatase
      inhibitors.
AB  - Calix[4]arenes bearing one or two methylenebisphosphonic acid fragments were
      prepared via addition of diethylphosphite to the parent calix[4]arene aldehydes.
      The resulting compounds displayed stronger inhibition of calf intestine alkaline
      phosphatase than simple methylenebisphosphonic or 4-hydroxyphenyl
      methylenebisphosphonic acids. The action of these phosphorylated calix[4]arenes
      is concordant with partial mixed-type inhibition. The inhibition constants Ki and
      Ki' for the calix[4]arene bis(methylenebisphosphonic) acid in Tris-HCl buffer at
      pH 9 are 0.38 microM and 2.8 microM respectively. The replacement of the
      phosphoric acid moieties on the macrocycle with diethylphosphonates results in a
      sharp decrease of its inhibitory action. Preorganizing phosphonic acid fragments
      using a calixarene platform therefore provides a promising approach for the
      design of efficient alkaline phosphatase inhibitors.

PMID- 15505725
TI  - The synthesis and crystal structures of halogenated tolans p-X-C6H4-C[triple
      bond]C-C6F5 and p-X-C6F4-C[triple bond]C-C6H5(X=F, Cl, Br, I).
AB  - A series of halogenated, partially fluorinated tolans of general formula p-X-C6H4
      C[triple bond]C-C6F5[X=I (1), Br (2), Cl (3), F (4)] and p-X-C6F4-C[triple bond]C
      C6H5[X=I (5), Br (6)] have been prepared via palladium-catalysed Sonogashira
      cross-coupling, or for X=Cl (7), by nucleophilic aromatic substitution reactions.
      The single-crystal X-ray structures of 1-3 and 5-6 have been determined. The
      structures reveal that the molecular packing is characterized by either arene
      perfluoroarene interactions (3), or halogen-halogen interactions (isomorphous 1
      and 2), or neither (isomorphous 5 and 6). The structure of represents the first
      fully determined crystal structure of a compound that contains a halogen atom
      other than fluorine, in which arene-perfluoroarene interactions are present.

PMID- 15505726
TI  - [Pre-medication for tracheal intubation].

PMID- 15505727
TI  - [The nutrition specialist's role in choosing special diets].

PMID- 15505728
TI  - [Cystic fibrosis in Brazil: the pediatrician's turn].

PMID- 15505729
TI  - [Sickle cell disease and infection].
AB  - OBJECTIVE: To discuss the high prevalence of sickle cell disease in our
      environment and the increased morbidity and mortality as a result of infection
      associated with this condition. SOURCES OF DATA: Review of MEDLINE from 1986 to
      2003. We found around 600 references about the subject. Thirty-five journal
      articles were reviewed, in addition to chapters in two text books. SUMMARY OF THE
      FINDINGS: We discuss general information concerning sickle cell disease as well
      as a few topics about the most frequently observed infections in these patients.
      Drug prophylaxis and immunizations are also covered. CONCLUSIONS: This review
      hopes to provide the pediatric community with information concerning the
      association between sickle cell disease and infections, so as to minimize the
      occurrence of complications.

PMID- 15505731
TI  - [Nutrient intake and nutritional status of children following a diet free from
      cow's milk and cow's milk by-products].
AB  - OBJECTIVE: To assess the food intake and the nutritional status of children on a
      cow's milk and cow's milk by-products free diet. METHODS: Twenty-six children
      receiving a cow's milk and cow's milk by-products free diet were assessed during
      their first visit to the Pediatric Gastroenterology Clinic (mean age = 19.1
      months). Thirty children with no food restriction (mean age = 16.8 months) were
      also assessed. The usual daily food intake method was used to make the dietary
      assessment. The food intake was compared between the groups and in relation to
      the Dietary Reference Intakes (DRIs). The z-scores for weight/age, height/age and
      weight/height were used to evaluate the nutritional status. RESULTS: The cow's
      milk free diet group presented lower energy (p = 0.005), protein (p < 0.001),
      lipid (p < 0.001), calcium (p < 0.001) and phosphorous (p < 0.001) intake when
      compared to the control group. The number of children who had energy, calcium and
      phosphorous intake below the DRIs was higher in the cow's milk free diet group
      than in the control group. The z-score means for the cow's milk free diet and
      control groups were, respectively: height/age -0.81+/-1.06 vs +0.42+/-1.25 (p <
      0.001), weight/age -1.03+/-1.21 vs +0.02+/-0.91 (p < 0.001), and weight/height 
      0.63+/-1.08 vs +0.30+/-1.11 (p = 0.004). CONCLUSION: During the cow's milk and
      cow s milk by-products exclusion therapy, qualitative and quantitative food
      intake monitoring must be carried out periodically, so as to prevent inadequacies
      in meeting nutritional requirements and impairment of growth and development.

PMID- 15505730
TI  - [Assessment of intubation procedures at reference pediatric and neonatal
      intensive care units].
AB  - OBJECTIVE: To describe intubation procedures in two pediatric and two neonatal
      intensive care units in the city of Porto Alegre. METHODS: Cross-sectional study
      divided into a retrospective and a prospective phase. All intubations performed
      in these units during a 6-month period were considered. Data were collected by
      interviewing the physician responsible for the procedure and reviewing the
      patients' charts, including drugs administered, sedation status, number of
      attempts, difficulties and complications during the procedure. Data were analyzed
      using the t test and the Mann-Whitney test for continuous variables and the chi
      square test for categorical variables, considering a p < 0.05. RESULTS: Sedatives
      were administered in 89.5% of the 134 pediatric procedures and 24% of the 116
      neonatal procedures (p < 0.001). Muscle relaxants were prescribed for 3% of the
      children and 0.9% of the neonates. Only 53.7% of the children and 31.9% of the
      neonates were considered as adequately relaxed. The children who were
      inadequately relaxed had more intubations attempts (2.4-/+1.3 vs 1.7-/+1.2 p =
      0.001), became more hypoxemic (20.9 vs 5.5% p = 0.015) and were more difficult to
      intubate (54.8 vs 25% p < 0.001). There were more urgent cases and more
      intubations attempts (2-/+1.2 vs 1.5-/+0.9 p = 0.036) among the inadequately
      relaxed neonates. Difficulties and complications occurred in 38.8 and 28.3% of
      the pediatric cases and 29 and 12% of the neonatal cases, respectively.
      CONCLUSIONS: There was no established routine for intubation procedures in the
      units studied, and the use of muscle relaxants was not usual. The absence of
      adequate muscle relaxation is associated with more intubation attempts,
      difficulties and hypoxemia during the intubation procedure.

PMID- 15505732
TI  - [Cystic fibrosis at a Brazilian center of excellence: clinical and laboratory
      characteristics of 104 patients and their association with genotype and disease
      severity].
AB  - OBJECTIVE: To identify the clinical, laboratory and radiographic characteristics
      of the cystic fibrosis patients under care at Universidade Estadual de Campinas
      (UNICAMP) in the last decade of the twentieth century, and to investigate the
      association of these characteristics with genotype and severity of the disease as
      measured by the Shwachman score. METHODS: Descriptive, retrospective and cross
      sectional study of the patients assisted at UNICAMP hospital's Cystic Fibrosis
      Clinic from July 1990 to July 2000. RESULTS: One hundred and four patients were
      studied; 53.8% male; 93.3% Caucasian; 89.4% presented with respiratory symptoms;
      59.6% presented with digestive symptoms; 5.8% had meconium ileus; 4.8% had
      diabetes. The mean age at onset of symptoms was 3 months, and the mean age at
      diagnosis was 2 years and 4 months. At diagnosis, 69.9 and 56.6% of the patients
      had weight and height below 10th percentile, respectively; in 10.6%, sweat
      chloride was < 60 mEq/l. Staphylococcus aureus was found in 80.2%, Pseudomonas
      aeruginosa in 76%, and Burkholderia cepacia in 5.2%. DeltaF508 homozygosis was
      observed in 18.75%, whereas 62.50% of the patients were DeltaF508 heterozygous. A
      moderate/severe Shwachman score was found in 15.7%. Eighteen patients died in
      that period (17.3%). The mean age at death was 7 years and 8 months; median
      survival after diagnosis was 18 years and 4 months. Patients who have at least
      one DeltaF508 mutation have more frequent alterations in fecal fat levels when
      compared to patients who do not have this mutation (p < 0.05). There were no
      differences in any parameter between DeltaF508 homozygous and heterozygous
      patients. CONCLUSIONS: The clinical and laboratory characteristics of the 104
      patients studied were similar to the characteristics described for patients in
      other countries. Exceptions are the higher age at diagnosis and lower survival.
      Our results support the recommendation for early diagnosis and the need for more
      treatment opportunities in the population of cystic fibrosis patients.

PMID- 15505733
TI  - [Validation of the Williams ultrasound scoring system for the diagnosis of liver
      disease in cystic fibrosis].
AB  - OBJECTIVES: To describe the hepatic abnormalities revealed by ultrasound
      examination of cystic fibrosis (CF) patients followed at the CF Outpatient Clinic
      at the Federal University of Minas Gerais; to compare ultrasound data with
      clinical and biochemical parameters; to validate the Williams ultrasound score
      for the diagnosis of liver disease in CF. METHODS: Seventy cystic fibrosis
      patients were followed prospectively and underwent clinical, biochemical and
      ultrasound examinations. The ultrasound findings were compared to the results of
      the clinical and biochemical examinations. Clinical and biochemical criteria were
      used as the gold standard for the validation of the Williams ultrasound score. We
      calculated the sensitivity, specificity, and positive and negative predictive
      values for the Williams score. The patients were divided into two groups: normal
      (score = 3) or abnormal (score > 3) ultrasound examination. RESULTS: Ten patients
      met the clinical and/or biochemical criteria for liver disease (14.3%). All of
      them presented some abnormality on ultrasound examination of the liver.
      Abnormalities of the hepatic parenchyma, edge and periportal fibrosis were
      statistically more frequent in these patients. The Williams ultrasound score
      showed high specificity (91.7%; CI 80.9-96.9), but low sensitivity (50%; CI 20.1
      79.9) for the diagnosis of liver disease. CONCLUSIONS: The Williams ultrasound
      score was not a good screening tool when compared to the clinical and biochemical
      examinations. Since there are currently no adequate tests that can be used to
      diagnose liver disease, we recommend a sequential evaluation combining clinical,
      biochemical and ultrasound examinations for the diagnosis of liver disease in CF.

PMID- 15505734
TI  - [Evaluation of the influence of patient age and spacer device volume on aerosol
      lung deposition].
AB  - OBJECTIVE: To evaluate the efficacy of three frequently used spacer devices to
      deliver aerosol to the lung, and to compare radioaerosol deposition with each
      device in different age groups. METHODS: Nine healthy, non-smoking volunteers
      were recruited: three adults and six children, including three toddlers and three
      school age children. Qualitative and semi-quantitative analysis of radioaerosol
      deposition in the lung were carried out. Yet, two small-volume devices
      (Aerochamber and Inal-Air) and one large-volume device (Flumax) were compared.
      Each patient inhaled 99mtechnetium-phytate. The device was filled during 30
      seconds with radioaerosol. Oxygen was used as the driving gas. During 10 seconds,
      the patients inhaled the radioaerosol. The radiation emitted at the front and
      back of the chest was measured. The radiation inside the device was also
      measured. RESULTS: The quantitative evaluation of lung deposition revealed that
      the younger the patient, the less aerosol was deposited in the lung with the
      large-volume spacer device (Flumax). The difference between small-volume devices
      (Aerochamber and Inal-Air) was not significant. CONCLUSION: Small-volume spacers
      are the most appropriate for children. Large-volume devices should only be used
      by adolescents and adults.

PMID- 15505735
TI  - [Asthma in schoolchildren from Recife, Brazil. Prevalence comparison: 1994-95 and
      2002].
AB  - OBJECTIVES: To describe the prevalence of asthma and asthma variants in
      schoolchildren from Recife in 2002, and to compare these data with data from 1994
      95; to analyze the relationship between maternal schooling and the presence of
      asthma or worsening asthma; and to evaluate the diagnostic accuracy of the yearly
      prevalence of wheezing as an asthma indicator. METHODS: Cross-sectional study. A
      probabilistic sample of 3,086 and 2,774 13- and 14-year-old students answered a
      written questionnaire in 1994-95 and 2002, as part of the International Study of
      Asthma and Allergies in Childhood. RESULTS: The following prevalence rates were
      observed in 1994-95 and 2002, respectively: cumulative prevalence of referred
      asthma: 21 vs 18.2%; cumulative prevalence of wheezing: 39 vs 38%; yearly
      prevalence of wheezing: 19.7 vs 19.4%; yearly prevalence of night cough: 31 vs
      38%; yearly prevalence of exercise-induced wheezing: 20.6 vs 23.8%. The yearly
      prevalence of asthma attacks was 16.3 vs 15.2% for 1 to 3 attacks; 2.7% vs 1.2%
      for 4 to 12 attacks; and 1% vs 0.4% for more than 12 attacks. The yearly
      prevalence of attacks that disturbed sleep was 13 and 10.3%. The yearly
      prevalence of attacks with compromised speech was 4.8 and 4.1%. Higher levels of
      maternal schooling were related to higher cumulative prevalence of referred
      asthma and to cumulative and yearly prevalence of wheezing. CONCLUSIONS: The
      prevalence of asthma and its severe forms is high in teenager students in Recife.
      It is also related to higher levels of maternal schooling.

PMID- 15505736
TI  - [A comparison of the continuous positive airway pressures produced by two
      systems].
AB  - OBJECTIVE: To compare the generation of continuous positive airway pressure using
      a hand-made device (underwater seal) or a ventilator (Inter 3). METHOD: Two
      positive airway pressure generation systems were compared through laboratory
      simulations. Measurements were not considered if the mechanical ventilator
      required calibration or in the presence of gas flow variation (flowmeter sphere
      oscillation). Recordings were assessed in terms of the capacity to produce the
      desired pressure (3, 5 and 6 cmH2O) when submitted to three different flow values
      (8, 10 and 12 l/min). For that end, Student's t test for paired samples and the
      nonparametric Man-Whitney test for independent samples were employed. RESULTS: We
      verified that the systems behave in different manners under the same conditions
      of flow and positive end expiratory pressure. For the mechanical ventilator, the
      mean pressure behavior under continuous positive airway pressure at 3 cmH2O with
      flows of 8, 10 and 12 l/min were 2.26+/-0.41, 2.22+/-0.37, 2.04+/-0.41,
      respectively; under positive end-expiratory pressure at 5 cmH2O we found 3.96+/
      0.41, 3.87+/-0.43 and 3.75+/-0.52; and under positive end-expiratory pressure at
      6 cmH2O the values recorded were 4.94+/-0.40, 4.85+/-0.41 and 4.72+/-0.37. For
      the underwater seal, the mean pressure behavior under continuous positive airway
      pressure at 3 cmH2O with flows of 8, 10 and 12 l/min were 4.24+/-0.24, 4.46+/
      0.26, 4.72+/-0.37, respectively; at 5 cmH2O the values were 5.97+/-0.17, 6.28+/
      0.18, 6.47+/-0.31; and at 6 cmH2O we recorded 6.85+/-0.20, 7.17+/-0.29 and 7.53+/
      0.31. All the comparisons were statistically significant (p = 0.000). CONCLUSION:
      Through our recordings it was possible to observe that the Inter 3 continuous
      positive airway pressure system was more stable than the underwater seal.

PMID- 15505737
TI  - The role of sample collection timing on interleukin-6 levels in early-onset
      neonatal sepsis.
AB  - OBJECTIVE: To assess different perinatal findings and sample collection timing in
      newborns with early-onset sepsis comparing those with low IL-6 levels to the ones
      with high levels. METHODS: Eighty-five newborn infants, with clinical signs of
      sepsis and/or positive blood cultures, had plasma IL-6 collected in the initial
      evaluation for early-onset sepsis in the first 96 hours of life. They were
      classified in two groups according to their plasma IL-6 levels: higher, and equal
      to or lower than IL-6 median value for the whole septic group. RESULTS: Median IL
      6 for the whole group was 89 pg/ml. High and low level groups were formed by 42
      and 43 newborns respectively. There were no differences between the two groups
      regarding gestational ages, birth weights, cesarean-section proportion, Apgar
      scores, number of neonates with maternal risk factors for infection, number of
      maternal intrapartum antibiotic therapy, and number of positive blood cultures.
      Median plasma IL-6 in the high level group was 287 pg/ml, and in the low level
      group 46 pg/ml (p < 0.001). Median sample timing was 17.5 hours of life for the
      high level group and 36 hours of life for the low level group (p < 0.001). There
      was a significant negative correlation coefficient between IL-6 levels and sample
      collection timing. CONCLUSION: Sample collection timing is an important factor
      for detection of high plasma IL-6 level in newborn infants with early-onset
      sepsis.

PMID- 15505738
TI  - [Feeding habits of breastfed and non-breastfed children up to 1 year old].
AB  - OBJECTIVE: To describe the eating habits of breastfed and non-breastfed children
      through the analysis of food intake by children younger than one year of age in
      Feira de Santana in 2001. METHODS: Cross-sectional study. The mothers of children
      younger than one year answered a questionnaire during the national vaccination
      day in 44 (71%) vaccination units selected by simple stratification. 2,319
      children were evaluated, representing 24.3% of the estimated population.
      Prevalence ratio and 95% confidence interval were calculated. Statistical
      significance was determined using the chi-square test. RESULTS: Non-breastfed
      children aged four months or younger were 8.2 and 6.7 times more likely to
      receive the family food (95% CI: 3.23-20.66) or vegetable soup (95% CI: 3.84
      11.78), respectively. In the same age group, the prevalence of non-breastfed
      children receiving water, juice, and fruit was significantly higher in relation
      to breastfed children (70.7% vs 19.7%, 63.3% vs 26.7%, 33.3% vs 4.9% and 14.4% vs
      1.4%, respectively). CONCLUSION: Breastfed children had healthier habits than non
      breastfed children in terms of the introduction of complementary foods.

PMID- 15505739
TI  - [Growth velocity of preterm appropriate for gestational age newborns].
AB  - OBJECTIVE: To assess the growth velocity of preterm appropriate for gestational
      age newborns through growth curves. METHOD: A longitudinal and prospective study
      was carried out at two state-operated maternity hospitals in Belo Horizonte. Two
      hundred and sixty appropriate for gestational age preterm infants with birth
      weight < 2,500 g were evaluated weekly for body weight, head circumference and
      length. Growth velocity curves were constructed based on the derivative of the
      mathematical equation of the Count's model applied to somatic growth. Two
      analyses were made in the present study: absolute velocity, i.e., weight gain
      (g/day), and head circumference and length gains (cm/week); and relative
      velocity, i.e., weight gain(g/kg/day), and head circumference and length gains
      (cm/m/week). RESULTS: The curves of weight gain (g/day) were proportional to
      birth weight (the lowest and the highest birth weight neonates gained 15.9 and
      30.1 g/day, respectively). The curves of weight gain (g/kg/day) were inversely
      proportional to birth weight with increasingly higher rates of weight gain
      between the first and fourth weeks (during the third week, the lowest and the
      highest weight newborns gained 18 and 11.5 g/kg/day, respectively). Later there
      was a drop, and by the 12th week the rates were similar for all groups (7.5 to
      10.2 g/kg/day). The curves of relative velocity (cm/m/week) for head
      circumference and length were inversely proportional to birth weight; the lower
      weight preterm newborns had, the higher head circumference and length growing
      rates were, compared with those with more weight. CONCLUSION: The relative
      velocity is the best parameter to describe the growth dynamics of preterm
      infants, especially of those with lower birth weight. Lower birth weight infants
      gained more weight, head circumference and length.

PMID- 15505740
TI  - [Autosomal chronic granulomatous disease: case report and mutation analysis of
      two Brazilian siblings].
AB  - OBJECTIVE: To report the case of two siblings with chronic granulomatous disease.
      Chronic granulomatous disease is a primary immunodeficiency disorder
      characterized by abnormal microbicidal activity. Mutations in the p47-phox gene
      (NCF-1) are present in about 30% of the patients with chronic granulomatous
      disease; this group presents a better prognosis and later onset of recurrent
      infections as compared with the X-linked variant, present in about 56% of
      patients. DESCRIPTION: Case 1 is a female presenting repeat infections since age
      10, starting with impetigo followed by severe pneumonia six months later. The
      severity of the lung infection associated with liver abscess and the patient's
      resistance to treatment prompted laboratory investigation for immunodeficiency.
      The results of the nitroblue tetrazolium and superoxide release tests were
      consistent with a diagnosis of chronic granulomatous disease. The parents and
      siblings were assessed, revealing the presence of granulomatous disease in a
      brother (Case 2). He also presented repeat infections with impetigo at age 10,
      followed by pneumonia six months later, however in a non severe form. Single
      strand conformational polymorphism analysis detected abnormal electrophoretic
      mobility of exon 2 of the NCF-1 gene. Sequence DNA analysis revealed a
      dinucleotide GT deletion in exon 2. COMMENTS: It is important to evaluate the
      relatives of chronic granulomatous disease patients, even in the absence of
      typical clinical signs. Defining the mutation and its correlation with phenotype
      is important to provide appropriate genetic counseling and clinical prognosis.

PMID- 15505741
TI  - [Mental retardation].

PMID- 15505744
TI  - [Neonatal networks].

PMID- 15505745
TI  - [Childhood obesity -- How can we be efficient?].

PMID- 15505746
TI  - Functional psychosis in childhood and adolescence.

PMID- 15505748
TI  - Functional brain imaging in Parkinson's disease-overview.

PMID- 15505749
TI  - A prospective study of alcoholism and the risk of Parkinson's disease.
AB  - The lower incidence of Parkinson's disease (PD) among smokers may be explained by
      a protective effect of cigarette smoke, or by a tendency to avoid addictive
      behaviors among future PD cases. We conducted an indirect test of the latter
      hypothesis by comparing the incidence of PD between alcoholics and nonalcoholics
      in the General Practice Research Database of the United Kingdom. Our case-control
      study included 1,019 cases and 10,123 matched controls. Overall, we did not find
      a lower incidence of PD among alcoholics compared with nonalcoholics (odds ratio:
      1.09; 95 % CI: 0.67, 1.78).

PMID- 15505750
TI  - Life style risks of Parkinson's disease: association between decreased water
      intake and constipation.
AB  - Gastrointestinal dysfunction, especially constipation, is one of the major
      problems in the daily life of patients with Parkinson's disease (PD). About 60 to
      80% of PD patients suffer from constipation. Several studies have proven that
      constipation appears about 10 to 20 years prior to motor symptoms. More recently,
      Abbott et al. have found from a large scale prospective study that lower
      frequency bowel movements predict the future risk of PD. Furthermore, Braak et
      al. have found that Lewy neuritis and Lewy bodies, the hallmarks of PD pathology,
      appear in the dorsal nucleus of vagus in the earliest stage of the disease and
      then extend upward through the brain stem to reach the substantia nigra in the
      third stage. They also hypothesize that some yet undefined toxins break through
      the mucosal barrier of the intestine and are incorporated into the axon terminal
      of the vagus nerve and transported in a retrograde manner to the vagus nucleus.
      In this study, we assessed bowel movements and nutritional status in Japanese
      patients with PD. We found that intake of water was significantly decreased in PD
      patients from early life and associated with their constipation. Ninety four
      patients with PD (M 50, F 44) were enrolled. Nutritional status was assessed
      using the Self-administered Diet History Questionnaire (DHQ). Total water intake
      was calculated from the consumption of coffee, green tea, and tea. We also
      questioned the behavior of water drinking from the early stage of life. The
      questionnaire for bowel movements concerned the frequency of defecation, age of
      onset of constipation, and age of onset of motor dysfunction. Less than one bowel
      movement in 3 days was defined as constipation. The nutritional status of PD
      patients did not differ significantly from those of controls though several
      studies have shown excess intake of animal fats or reduced consumption of coffee
      are risks in PD. In contrast, water intake was significantly lower in PD patients
      than controls (604.0+/-377.2 ml/d vs 909.5+/-531.6 ml/d; P<0.0001).
      Interestingly, PD patients tended not to feel thirsty and thus they had no desire
      to drink water throughout their life. Seventy four patients out of 94 (78.7 %)
      complained of constipation. Mean bowel frequency was once per 3.3+/-1.1 days and
      71.1% of patients were defined as having constipation. Women suffered from
      constipation more frequently than men (82.4% vs 61.9 %). In 33 patients out of 74
      (44.6 %), onset of constipation preceded motor disturbance by an average time of
      18.1+/-18.8 years. Furthermore, the amount of water intake correlated inversely
      with the severity of constipation and the depletion of water intake preceded
      constipation in most cases. The present results support previous findings that
      constipation precedes the onset of motor dysfunction in PD. To our knowledge,
      this is the first report to point out latent water depletion in PD patients. It
      is not certain at present whether coffee or caffeine themselves are the
      protective factor for PD or alternatively the amount of water in coffee drinking
      is more essential. Prospective studies on a large scale are necessary to
      elucidate the real meaning of water depletion in PD.

PMID- 15505751
TI  - Session 3 "Analyzer Workshop" evolution of therapeutic strategies in Parkinson's
      disease.

PMID- 15505752
TI  - Assessment of disease progression in parkinsonism.
AB  - In this brief article, we report preliminary results from an NIH-funded project
      to use functional brain imaging to study the natural history of neurodegeneration
      during the earliest clinical stages of PD. We used positron emission tomography
      (PET) to measure DAT binding (18F-FPCIT), resting glucose metabolism (18FFDG),
      and brain activation (H215O) responses in 20 newly diagnosed PD patients. The
      longitudinal study is being conducted at three time points for each measurement
      during a 5-year period. The interim results indicate the evolution of abnormal
      metabolic brain networks and activation responses occurring in parallel with
      presynaptic nigrostriatal dopamine dysfunction in early PD.

PMID- 15505753
TI  - Neuroimaging trials of Parkinson's disease progression.

PMID- 15505756
TI  - Global risk management in type 2 diabetes: blood glucose, blood pressure, and
      lipids--update on the background of the current guidelines.
AB  - Diabetes mellitus presents a significant public health burden based on its
      increased morbidity, mortality, and economic cost. The high comorbidity and
      prevalence of concomitant diseases like hypertension and dyslipidemia in diabetic
      patients cause the high risk in developing secondary, cost intensive, and for the
      patient often disastrous late complications (nephropathy, retinopathy,
      neuropathy, and cardiovascular disease). Therefore, patients with diabetes
      mellitus need a global risk management that takes the various individual clinical
      problems into account. The current global standards of therapy in patients with
      diabetes mellitus are focused on the control of glycemia, blood pressure, and
      lipid levels, as well as aspirin therapy and avoiding of smoking. There are a
      number of guidelines and recommendations to manage these global issues. Our
      review will summarize current recommendations and consolidate therapeutic goals
      and treatments that are of vital importance in the global risk management in
      diabetic patients.

PMID- 15505757
TI  - A detailed investigation of hirsutism in a Turkish population: idiopathic
      hyperandrogenemia as a perplexing issue.
AB  - Hirsutism is a common clinical problem in women and the treatment depends on the
      cause of hirsutism. The study was designed to determine the various causes of
      hirsutism and their prevalences in a Turkish population. 168 women with hirsutism
      attending to Endocrinology Outpatient Clinic of Erciyes University Hospital were
      investigated in detail. Medical history, physical examination, and basal levels
      of free testosterone (fT), androstenedione, follicle-stimulating hormone (FSH),
      luteinizing hormone (LH), dehydroepiandrosterone-sulphate (DHEAS), 17
      hydroxyprogesterone (17-OHP), 11-deoxycortisol (11-S), thyroid hormones, thyroid
      stimulating hormone (TSH), and prolactin were determined. ACTH stimulation test
      was performed for the diagnosis of non-classic congenital adrenal hyperplasia
      (NCAH). Pelvic/vaginal and adrenal ultrasonographies were performed for the
      detection of tumors and polycystic ovarian changes. Polycystic ovary syndrome
      (PCOS) was diagnosed in 96 (57.1 %) patients, idiopathic hirsutism in 27 (16 %),
      NCAH in 12 (7.1 %), adrenal carcinoma in 3 (1.8 %), and Cushing's disease in 1
      (0.6 %) patient. Among patients with NCAH, 11 (91.7 %) patients had 11-beta
      hydroxylase (11-beta OH) deficiency, and 1 (8.3 %) had 21-hydroxylase deficiency.
      The etiology of hyperandrogenemia was not clear in 29 (17.4 %) patients and these
      patients were named as idiopathic hyperandrogenemia. The clinical presentation of
      11-beta OH deficiency is indistinguishable from that of other hyperandrogenic
      states and ACTH stimulation test is the only way to diagnose this entity.
      Although PCOS is the most common cause of hirsutism, it is notable that nearly
      one fifth of hirsute women have no apparent cause of hyperandrogenemia.

PMID- 15505758
TI  - Prediction of relapse after antithyroid drug therapy of Graves' disease: value of
      color Doppler sonography.
AB  - Opinions differ regarding the indications for antithyroid drugs, radioiodine and
      surgery in patients with Graves' disease because the likelihood of long-term
      remission after medical treatment cannot be predicted. The aim of this study was
      to assess the value of quantifying thyroid blood flow in an attempt to predict
      outcome following withdrawal of antithyroid drug therapy. Spectral Doppler
      recordings were obtained from the thyroid arteries in 24 patients with Graves'
      disease at the time of diagnosis. Thyroid blood flow levels measured at the time
      of diagnosis of Graves' disease were correlated with outcome following withdrawal
      of medical treatment (mean duration of treatment: 14 months). Clinical follow-up
      for at least 18 months (range: 18 - 39 months) after antithyroid drug withdrawal
      was possible in 13 patients (12 women). Mean peak systolic velocity and volume
      flow rate values as well as thyroid volume measured at the time of diagnosis were
      significantly higher (139 cm/s, SD 46; 195 ml/min, SD 170; 52 ml, SD 18) in
      patients who relapsed after drug treatment compared with patients in remission
      (71 cm/s, SD 27; 67 ml/min, SD 61; 25 ml, SD 13). The correlation between thyroid
      blood flow measurements and thyroid volume was high (r = 0.79 - 0.96). Recurrence
      of disease could be predicted with a sensitivity of 71 % and a specificity of 100
      % based on thyroid blood flow measurements. This preliminary data suggest that
      quantification of thyroid blood flow by means of Doppler sonography might be a
      useful tool to predict the outcome of Graves' disease following withdrawal of
      medical treatment and could be helpful in finding the adequate kind of therapy.

PMID- 15505759
TI  - In vivo properties of the urinary bladder wall and their modulation by estradiol
      and raloxifene in a rat model.
AB  - OBJECTIVES: Urinary incontinence is a common symptom of urogenital aging that
      affects a considerable proportion of postmenopausal women. Morphological and
      morphometrical modulation of the bladder by estrogen are known. Yet data showing
      that this translates into changes of in vivo function of the urinary bladder are
      missing. METHODS: We measured urodynamic parameters in anaesthetized, surviving
      rats. Following ovariectomy animals were divided into three groups and fed either
      an estradiol-, raloxifene-, or unsupplemented soy-free formula for ten weeks. Via
      a transurethral catheter the intravesical pressure was recorded during a stretch
      period (the urinary bladder was filled), and a one-minute isometric accommodation
      period immediately after the filling period. Upon termination of the experiment
      upper and lower halves of the bladder were processed histologically. RESULTS: The
      estrogen-, and raloxifene-treated animals showed significantly higher pressures
      in responses to rapid stretch. Bladder compliance during the isometric period on
      the other hand was not significantly affected by these treatments. Thickness of
      the epithelial layer, collagen content and muscle bundles were significantly
      increased by estrogen and raloxifene treatment. CONCLUSIONS: This is a good
      animal model to investigate modulation of detrusor muscle contractility and
      stiffness. Both estradiol and raloxifene increase bladder contractility. Urinary
      bladder morphology indicates that estrogen acts primarily in the upper half of
      this organ since significant effects on collagen content and muscle fibers are
      only found in this part.

PMID- 15505760
TI  - Insulin secretion is stimulated by ethanol extract of Anemarrhena asphodeloides
      in isolated islet of healthy Wistar and diabetic Goto-Kakizaki Rats.
AB  - BACKGROUND: The hypoglycemic effect of extract of Anemarrhena asphodeloides has
      been accounted for by the substance mangiferin which increases insulin
      sensitivity. The present study aimed to investigate whether an ethanol extract of
      Anemarrhena asphodeloides would stimulate insulin secretion and if so, further
      elucidate the mechanism behind this effect. METHODS: Isolated pancreatic islets
      of normal Wistar rats and spontaneously diabetic Goto-Kakizaki (GK) rats were
      batch incubated or perifused to study effect of Anemarrhena asphodeloides extract
      (TH2) on insulin release. RESULTS: At 3.3 mM glucose, 2, 4, and 8 mg/ml TH2
      increased the insulin release of Wistar rat islets 2.5-, 4.1-, and 5.7-fold,
      respectively (p < 0.05) and of GK rat islets 1.7-, 3.0-, and 6.3-fold,
      respectively (p < 0.01). Similarly at 16.7 mM glucose, 2, 4 and 8 mg/ml TH2
      increased insulin release of Wistar rat islets 1.5-, 2.2-, and 3.8-fold,
      respectively (p < 0.05) and of GK rat 2.5-, 4.2-, and 11.9-fold, respectively (p
      < 0.01). In perifusions of islets, TH2 also increased insulin secretion that
      returned to basal levels when TH2 was omitted from the perifusate. Mangiferin had
      no effect on insulin secretion of islets. In islets depolarized by 30 mM KCl and
      B-cell K-ATP channels kept open by 0.25 mM diazoxide, TH2 (8 mg/ml) further
      enhanced insulin secretion at 3.3 but not at 16.7 mM glucose. Pertussis toxin
      suppressed the insulin stimulating effect of 2 and 8 mg/ml TH2 by 35 % and 47 %
      (p < 0.05 and p < 0.001, respectively). CONCLUSIONS: Ethanol extract of the roots
      of Anemarrhena asphodeloides contains a substance, TH2, that stimulates insulin
      secretion both at 3.3 and 16.7 mM glucose in islets of normal Wistar and diabetic
      GK rats. The mechanism behind TH2-stimulated insulin secretion involves an effect
      on the exocytotic machinery of the B-cell, mediated via pertussis toxin-sensitive
      Gi- (or Ge-) proteins.

PMID- 15505761
TI  - Change in the amputation profile in diabetic foot in a tertiary reference center:
      efficacy of team working.
AB  - Diabetic foot is a serious complication of diabetes mellitus and the risk of
      lower extremity amputation is very high in this population when compared with
      people without diabetes. We have previously reported the lower-extremity
      amputation rate and significant factors in determining the risks for patients who
      had been admitted to Hacettepe University Hospital, a tertiary reference center
      for Turkey, between the years 1992 and 1996. In January 2000, a diabetic foot
      care team including an infectious diseases specialist, orthopaedic surgeons,
      endocrinologists, a plastic and reconstructive surgeon, a radiologist, and a
      diabetic foot nurse was assembled. To determine whether a change has occurred in
      the rate and the risk factors of lower extremity amputations after the
      establishment of this team, medical records of 66 patients (39 men, 27 women)
      with diabetic foot who had been admitted to Hacettepe University Hospital between
      2000 and 2002 have now been retrospectively analysed. The grade distribution of
      diabetic foot according to Wagner classification was quite similar in the two
      studies (grade 1: 0 % vs. 4.5 %, grade 2: 15.6 % vs. 19.7 %, grade 3: 48 % vs.
      33.3 %, grade 4: 24.4 % vs. 30.3 %, grade 5: 11.5 % vs. 12.1 % in the former and
      current study, respectively). The overall amputation rate in the current study
      was 39.4 % (36.7 % in the former study). Ray amputation (35 %) and below-knee
      amputations (30 %) were the two most commonly applied procedures. The rates of
      Syme, above knee, other amputations (i.e., Boyd, talonavicular amputations and
      partial calcanectomy) were 8 %, 8 % and 19 %, respectively. These data suggest
      that amputation is still a frequently encountered outcome for our patients with
      diabetic foot, but the amputation profile has changed. The implementation of a
      diabetic foot care team has relatively decreased the rate of major amputations in
      an attempt for limb salvage to improve the quality of life of the patients.
      Presence of osteomyelitis, peripheral vascular disease and gangrene still remain
      as significant predictors of amputation in our population.

PMID- 15505762
TI  - Population-based measurement of quality of diabetes care using HbA1c values in
      the state of Thuringia/Germany.
AB  - INTRODUCTION/HYPOTHESIS: There remains insufficient knowledge about the quality
      of diabetes therapy regarding structure, process and outcome given by primary
      care in Thuringia, and elsewhere in Germany. The project assesses a means of
      determining the quality of diabetes therapy in primary care by analysis of HbA1c
      values within a broad territory. METHODS: HbA1c tests of Thuringian patients were
      analysed by 20 participating medical laboratories between January 1 and March 31,
      2002; each HbA1c test was identified by the postal code of the Thuringian General
      Practitioner (GP) who ordered the test and adjusted by a standardisation
      procedure (mean normal of healthy subjects 5 %). The German state of Thuringia
      (population of 2,421,871) consists of 23 urban and rural districts. This format
      was also used in the present study. RESULTS: Twenty participating laboratories
      contributed 59,702 HbA1c tests from diabetic patients in Thuringia. Adjusted mean
      HbA1c of entire Thuringia: 6.75 %, 36.4 % of all HbA1c tests were above 7.0 % and
      3,0 % of all HbA1c values above 10.0 %. Regional percentage of HbA1c tests above
      7.0 % ranged between 28.2 % and 47.3 %. Regional percentage of HbA1c tests above
      10.0 % ranged between 1.8 % and 4.8 %. Subgroup analyses comparing urban vs.
      rural districts showed significantly lower mean HbA1c (6.72 % vs. 6.75 %, CI 0.01
      - 0.06, p < 0.01) and percentage of HbA1c tests above 7 % (8.19 % vs. 8.24 %, CI
      0.01 - 0.08, p < 0.01) in urban areas. CONCLUSIONS: Mean HbA1c as an indicator of
      glycaemic control of diabetes patients in primary care in Thuringia was good. The
      percentage of patients who need immediate medical intervention to prevent acute
      complications varied between districts, which is indicative for differences in
      quality of diabetes care in Thuringia. However, the proposed method is still
      experimental and has not yet been evaluated. Consequently, considerable bias
      might influence the results.

PMID- 15505763
TI  - Failure of recombinant human growth hormone treatment to improve congestive heart
      failure in hypopituitarism.
AB  - Growth hormone (GH) deficiency decreases left ventricular (LV) contractility,
      induces LV chamber dilatation and promotes progression to congestive heart
      failure. It is, however, controversial, whether GH replacement therapy in
      addition to standard medical heart failure therapy should be considered as
      routine treatment in GH deficient patients with heart failure. In the present
      report of a 64-year-old GH deficient patient with heart failure, we demonstrate
      by using Doppler echocardiography, magnetic resonance imaging and 31P NMR
      spectroscopy that even a 12 month period of GH replacement therapy had no
      sustained effect on morphometric or functional parameters of LV performance nor
      on clinical signs or symptoms of heart failure. It is concluded that GH
      replacement therapy should currently not be regarded as standard heart failure
      therapy in patients with GH deficiency and should only be employed under careful
      monitoring including close follow-up in a standardized way.

PMID- 15505764
TI  - Topical application of nerve growth factor in human diabetic foot ulcers. A study
      of three cases.
AB  - Three diabetic patients with leg or foot ulcers unresponsive to conventional
      therapies were treated with topical application of Nerve Growth Factor (NGF). The
      results showed that NGF promotes healing after 5-14 weeks of treatment. This
      study suggests that the use of topical application of NGF may represent a new
      useful tool for the management of difficult diabetic ulcers.

PMID- 15505768
TI  - Autoantibody explosion in systemic lupus erythematosus: more than 100 different
      antibodies found in SLE patients.
AB  - OBJECTIVE: Description of the various autoantibodies that can be detected in
      patients with systemic lupus erythematosus (SLE). METHODS: A literature review,
      using the terms "autoantibody" and "systemic lupus erythematosus", was conducted
      to search for articles on autoantibodies in SLE, their target antigens,
      association with disease activity, or other clinical associations. RESULTS: One
      hundred sixteen autoantibodies were described in SLE patients. These include
      autoantibodies that target nuclear antigens, cytoplasmic antigens, cell membrane
      antigens, phospholipid-associated antigens, blood cells, endothelial cells, and
      nervous system antigens, plasma proteins, matrix proteins, and miscellaneous
      antigens. The target of autoantibody, the autoantigen properties, autoantibody
      frequencies in SLE, as well as clinical associations, and correlation with
      disease activity are described for all 116 autoantibodies. CONCLUSIONS: SLE is
      the autoimmune disease with the largest number of detectable autoantibodies.
      Their production could be antigen-driven, the result of polyclonal B cell
      activation, impaired apoptotic pathways, or the outcome of idiotypic network
      dysregulation.

PMID- 15505769
TI  - Autoimmune sensorineural hearing loss: clinical course and treatment outcome.
AB  - BACKGROUND: Autoimmune sensorineural hearing loss (ASHL) originally was defined
      both by the presence of progressive hearing loss (with or without vertigo) and a
      positive response to glucocorticoid therapy. Subsequently, antibodies to a 68-kd
      inner-ear antigen were identified in a high percentage of patients with ASHL.
      OBJECTIVE: To analyze the disease progression and treatment outcome of ASHL.
      METHODS: Retrospective chart review of 30 patients with a diagnosis of ASHL
      referred to Texas Tech Rheumatology Clinic. All subjects were tested for anti-68
      kd antibody, had audiometric evidence of hearing loss, and were treated with
      glucocorticoids. RESULTS: The median duration from onset of symptoms to
      audiometric testing was 25.5 weeks (mean, 144 weeks; range, 3-1,040 weeks), and
      to testing for anti-68-kd antibody was 40 weeks (mean, 157.3; range, 4-1,092
      weeks). Ninety percent of subjects tested positive for anti-68-kd antibodies. By
      audiometric testing, 50% of subjects were steroid-responsive; minimal improvement
      or no change was recorded in 12%, and worsening occurred in 39% after steroid
      therapy. The 3 subjects who were anti-68-kd antibody-negative were steroid
      unresponsive, and 1 progressed to complete deafness. CONCLUSIONS AND RELEVANCE:
      This series of patients with ASHL suggests a more variable and benign course with
      a better prognosis than previously reported. Immunosuppressive therapy other than
      steroids rarely was required, and rapid progression to complete hearing loss was
      very uncommon in this cohort.

PMID- 15505770
TI  - Immune-mediated inner ear disease: 10-year experience.
AB  - BACKGROUND: Autoimmune inner ear disease (AIED) was first described in 1979 and
      the disease has become more widely recognized over the last decade. Limited
      information is available regarding clinical features of the disease, disease
      course, and response to treatment. OBJECTIVE: To analyze data from 42 patients
      with documented immune mediated inner ear disease to further define this
      syndrome. METHODS: A retrospective chart review was conducted on all patients
      considered to have AIED by the Otolaryngology division physicians and on all
      patients positive for antibody testing to inner ear antigens from 1990 to 1999.
      Patients who were antibody positive with a clinical diagnosis of AIED were
      included in this review. RESULTS: Patients with AIED presented with rapidly
      progressive, frequently bilateral (79%), often fluctuating sensironeural hearing
      loss. Mean age at presentation was 50 years (22-80) with no gender predilection.
      Tinnitus (83%), vestibular complaints (79%), and Menieres (50%) were common
      concomitant symptoms along with hearing loss. Seven of 42 (17%) of the patients
      had evidence for other systemic autoimmune disorders. In 4 of the patients the
      onset of vestibuloauditory complaints preceded the diagnosis of autoimmune
      disorder. Thirty-three of 42 demonstrated antibodies to inner ear antigens but
      other autoantibodies were infrequent except in patients with systemic autoimmune
      disorders. Twenty-three of 33 (70%) of patients treated with corticosteroids
      improved clinically, often short-term. Sixteen patients received treatment with
      other immunosuppressive drugs including methotrexate, cyclophosphamide,
      azathioprine, mycophenolic mofetil, and intravenous immunoglobulin (IVIg)
      generally with a limited modest response. Using clinical trial criteria for
      response, only 5/35 (14%) demonstrated improvement over a mean 34.4 months follow
      up. CONCLUSIONS: Immune-mediated inner ear disease is not a uniform disease with
      simple diagnosis or treatment. The course of the disease often results in
      significant long-term disability due to hearing loss and response to aggressive
      immunosuppression including corticosteroids is poor.

PMID- 15505771
TI  - The outcome of pregnancy in the wives of men with familial mediterranean fever
      treated with colchicine.
AB  - OBJECTIVE: To evaluate the outcome of pregnancies of normal women married to men
      with familial Mediterranean fever (FMF), some of whom took colchicine during the
      conception with their wives. PATIENTS AND METHODS: We followed the outcome of
      pregnancies and deliveries of 60 wives of FMF patients; 53 of the husbands were
      taking colchicine during that time. As a control group we screened the outcome of
      pregnancy and delivery from 230 healthy women married to healthy men. RESULTS:
      The 60 FMF patients- wives had 222 pregnancies, of which 206 ended in term
      delivery with 209 live births. Sixteen pregnancies ended in spontaneous abortions
      (7%). Three of the newborns in the study group were born with congenital
      malformations. In the control group, of 788 pregnancies, 127 ended in abortions
      (16%). Six of the newborns were born with congenital malformations. The rate of
      the late abortions (second trimester) in both groups was comparable. CONCLUSIONS:
      The results of our study indicates that neither FMF nor colchicine increases the
      rate of abortions or congenital malformations. Therefore we believe that there is
      no need to discontinue colchicine treatment in men with FMF before the conception
      with their wives.

PMID- 15505772
TI  - Lack of association between the HLA-DRB1 locus and post-streptococcal reactive
      arthritis and acute rheumatic fever in Italian children.
AB  - OBJECTIVE: Post-streptococcal reactive arthritis (PSReA) may be a variant of
      acute rheumatic fever (ARF), but there still is debate on the relationship
      between the 2 entities. Possible associations with HLA class II antigens of PSReA
      (DRB1*01) and ARF (DRB1*16) were described previously in white Americans. To
      confirm these findings, we studied DRB1 alleles in a group of Italian children
      with PSReA and ARF. METHODS: We performed low-resolution HLA-DRB1 typing by a
      sequence-specific primer polymerase chain reaction method in 33 children with
      PSReA and 25 children with ARF. We also compared the DRB1 genotypes of our
      patients with 200 normal subjects from the same geographic area and typed in the
      same laboratory with the same methods. RESULTS: The allele distributions at the
      DRB1 locus observed in PSReA patients, ARF patients, and controls were not
      significantly different from each other (chi-square test with small numbers, P =
      .65). The positivity for each of the 13 HLA-DRB1 alleles was compared in disease
      groups (PSReA and ARF) and controls, and failed to show any significant
      association. Comparisons of the frequency of the DRB1*01 allele among PSReA, ARF,
      and controls did not show any statistical differences. No significant difference
      in the frequency of DRB1*16 was present between ARF vs the control group, between
      ARF vs PSReA, and in PSReA patients when compared with controls. CONCLUSIONS: Our
      data do not confirm in Italian patients the previously reported associations of
      DRB1*01 and DRB1*16 with PSReA and ARF, respectively.

PMID- 15505773
TI  - Septic arthritis in the adult caused by Streptococcus pneumoniae: a report of 4
      cases and review of the literature.
AB  - OBJECTIVES: To identify coexistent diseases, clinical features, approaches to
      management, and predictors of outcome in patients with pneumococcal septic
      arthritis. METHODS: Case series of 4 adults with Streptococcus pneumoniae septic
      arthritis seen at a university hospital, plus a review of 115 adults with
      pneumococcal septic arthritis reported in the medical literature from 1973
      through 2003. RESULTS: Among our 4 patients, 3 had polyarticular infections,
      joint prostheses were involved in 1, 3 had underlying joint diseases, and 1 had
      concurrent meningitis. Infection was caused by penicillin
      intermediate/cephalosporine-susceptible S pneumoniae in 1 patient and penicillin
      resistant/cephalosporine-intermediate S. pneumoniae in 1 patient. After a mean
      treatment duration of 6 weeks, all patients were clinically cured of infection.
      Review of the literature identified 115 cases of S pneumoniae septic arthritis in
      adults. Clinical data were available for 107 patients. Twenty-nine cases were
      polyarticular (26%), joint prostheses were involved in 15 patients (13%), and 61
      patients had underlying joint disease (57%). Meningitis was a concurrent
      infection in 15 cases. The presumed primary focus of infection was the
      respiratory tree in 44 patients. Ninety-six percent of cases were caused by
      penicillin-susceptible organisms. Cure of infection with survival was achieved in
      83% (79 of 95) of patients with native joint septic arthritis and in 67% (8 of
      12) of patients with prosthetic joint infection. A good functional outcome (full
      range of motion or return to baseline range of motion) after infection was
      achieved by 44 of 71 patients (62%) with native joint infection and by 4 of 7
      patients (57%) with infections of prosthetic joints. The likelihood of cure of
      infection or good functional outcome was not influenced by method of joint
      drainage. CONCLUSIONS: S pneumoniae is an uncommon, but not rare, cause of septic
      arthritis in the adult. Many patients have underlying joint disease (especially
      rheumatoid arthritis) and coexistent alcoholism. Although most infections involve
      native joints, prosthetic joint infections comprise 13% of cases. Polyarticular
      disease occurs in approximately one quarter of patients. Most patients have a
      preceding or concurrent extra-articular focus of pneumococcal infection. To date,
      the majority of reported infections are caused by penicillin-susceptible
      organisms, so penicillin G or a third-generation cephalosporine such as
      ceftriaxone remains the appropriate treatment option. However, infection with
      drug-resistant organisms is likely to be an increasing problem in the future.
      With directed antimicrobial therapy and appropriate joint drainage, the outcome
      is generally good for patients with native joint infections. In contrast, only
      two thirds of patients with infections of prosthetic joints survive their
      infections. Approximately 40% of surviving patients experience functional
      impairment or chronic pain as a sequelae of their infection.

PMID- 15505775
TI  - The resistance to ischemia of white and gray matter after stroke.
AB  - A contributing factor to the failure of trials of neuroprotectants in acute
      ischemic stroke may be the differing vulnerability to ischemia of white compared
      with gray matter. To address this issue, we determined to establish the existence
      of potentially viable tissue in white matter and its evolution to infarction or
      salvage in both gray and white matter compartments in patients with ischemic
      stroke. Twenty-seven patients (mean age, 73.4 years) at a median of 16.5 hours
      after symptom onset were studied using the hypoxic marker 18F-misonidazole with
      positron emission tomography (PET). Tissue was segmented using an magnetic
      resonance probabilistic map. Although there was a greater volume of initially "at
      risk tissue" in gray matter (58.3 cm3, 29.9-93.0 cm3 than white matter (42.0 cm3,
      15.8-74.0 cm3; p <0.001) at the time of PET imaging, a higher proportion of this
      was still potentially viable in white matter (41.4%, 4.6-74.5%) than in gray
      matter (23.6%, 3.2-61.1%; p <0.05). However, a similar proportion in each
      compartment spontaneously survived. These data provide evidence for the existence
      of potentially salvageable tissue in human white matter and is consistent with it
      having a similar or even greater resistance to ischemia than gray matter. For the
      latter possibility, alternative therapeutic strategies may be required for its
      salvage.

PMID- 15505776
TI  - Cardiac and respiratory failure in limb-girdle muscular dystrophy 2I.
AB  - Mutations in the gene encoding fukutin-related protein cause limb-girdle muscular
      dystrophy 2I. In this multicenter retrospective analysis of 38 patients, 55.3%
      had cardiac abnormalities, of which 24% had developed cardiac failure.
      Heterozygotes for the common C826A mutation developed cardiac involvement earlier
      than homozygotes. All patients initially improved while receiving standard
      therapy. Independent of cardiac status, forced vital capacity was below 75% in
      44.4% of the patients. There was no absolute correlation between skeletal muscle
      weakness and cardiomyopathy or respiratory insufficiency. These complications are
      a primary part of this specific type of limb-girdle muscular dystrophy, with
      important implications for management.

PMID- 15505777
TI  - Diphenylarsinic acid poisoning from chemical weapons in Kamisu, Japan.
AB  - We noted a new clinical syndrome with prominent cerebellar symptoms in apartment
      building residents in Kamisu, Japan. The well that provided drinking water
      contained diphenylarsinic acid, a degradation product of diphenylcyanoarsine or
      diphenylchloroarsine, which were developed for use as chemical weapons, inducing
      severe vomiting and sneezing. Characteristics of diphenylarsinic acid poisoning
      include brainstem-cerebellar and cerebral symptoms. Mental retardation associated
      with brain atrophy in magnetic resonance images was evident in some infants. We
      must be vigilant to prevent or minimize the effects of further diphenylarsinic
      acid poisoning in Japan or elsewhere.

PMID- 15505778
TI  - 3-hydroxy-3-methylglutaryl-CoA lyase deficiency in an adult with
      leukoencephalopathy.
AB  - 3-Hydroxy-3-methylglutaryl-CoA lyase deficiency is a disorder of leucine
      metabolism that usually presents with recurrent episodes of life-threatening
      hypoglycemia during early childhood. We report on a 36-year-old woman with
      seizures, recurrent metabolic disturbances, and severe leukoencephalopathy. The
      diagnosis was made by analysis of amino acids in urine and serum and was
      confirmed by demonstration of the deficient enzyme in cultured skin fibroblasts.
      The patient improved clinically on oral L-carnitine substitution. This treatable
      condition can remain unrecognized in adults and should be considered a potential
      cause of leukoencephalopathy.

PMID- 15505779
TI  - Maple syrup disease presenting as paroxysmal dystonia.

PMID- 15505780
TI  - A clinical trial of bromocriptine for treatment of primary progressive aphasia.

PMID- 15505782
TI  - Human endothelial cell attachment and proliferation on a novel vascular graft
      prototype.
AB  - A new vascular prosthesis prototype was assessed for its ability to support an
      endothelial cell layer in vitro. A coiled tubular structure, constructed from
      polymer-coated metallic wires, with an internal diameter of 690 microm, was used.
      Addition of heparin to the surface coating of the coil strongly enhanced the
      blood compatibility of the device. A series of coils with five different
      coatings, increasing in hydrophilicity, was studied. Heparin was added to one
      series, another series did not contain this anticoagulant drug. Upon contact with
      blood, a vascular prosthesis will instantaneously adsorb plasma proteins on its
      surface, and these proteins will influence the behavior of cells binding to the
      device. When coils were treated with human plasma proteins, mimicking the in vivo
      situation, human microvascular endothelial cells grew well on all coils studied,
      irrespective of the hydrophilicity of the underlying coating or the addition of
      heparin. For control coils, only endothelial cell growth on the most hydrophobic
      surfaces, and a moderate enhancing effect for heparin, were observed. This novel
      vascular graft prototype seems well suited for the support of an endothelial cell
      layer, especially when plasma proteins are adsorbed to its surface, and shows
      promise for in vivo testing.

PMID- 15505783
TI  - A population-based study of colorectal cancer test use: results from the 2001
      California Health Interview Survey.
AB  - BACKGROUND: Recent research has supported the use of colorectal cancer (CRC)
      tests to reduce disease incidence, morbidity, and mortality. A new health survey
      has provided an opportunity to examine the use of these tests in California's
      ethnically diverse population. The authors used the 2001 California Health
      Interview Survey (CHIS 2001) to evaluate 1) rates of CRC test use, 2) predictors
      of the receipt of tests, and 3) reasons for nonuse of CRC tests. METHODS: The
      CHIS 2001 is a random-digit dial telephone survey that was conducted in
      California. Responses were analyzed from 22,343 adults age >/= 50 years. CRC test
      use was defined as receipt of a fecal occult blood test in the past year and/or
      receipt of an endoscopic examination in the past 5 years. RESULTS: Nearly 54% of
      California adults reported receipt of a recent CRC test. Insurance coverage and
      having a usual source of care were the most important predictors of CRC testing.
      Latinos age < 65 years were less likely to be tested than whites (relative risk
      [RR], 0.84; 95% confidence interval [95% CI], 0.77-0.92). Men were more likely to
      be tested than women, an effect that was greater among individuals age 50-64
      years (RR, 1.28; 95% CI, 1.23-1.32) than among individuals age >/= 65 years (RR,
      1.19; 95% CI, 1.15-1.23). Women were more likely than men to say that their
      physician did not inform them the test was needed and that CRC tests were painful
      or embarrassing. CONCLUSIONS: Results of the current study indicate a need for
      physicians to recommend CRC testing to their patients. Assuring that all
      individuals have both health insurance and a usual source of care would help
      address gaps in the receipt of CRC tests.

PMID- 15505784
TI  - Racial differences in knowledge, attitudes, and cancer screening practices among
      a triracial rural population.
AB  - BACKGROUND: Low-income, minority, and rural women face a greater burden with
      regard to cancer-related morbidity and mortality and are usually underrepresented
      in cancer control research. The Robeson County Outreach, Screening and Education
      Project sought to increase mammography use among low-income, minority, and rural
      women age > 40 years. The current article reports on racial disparities and
      barriers to screening, especially those related to knowledge, attitudes, and
      behaviors. METHODS: A baseline survey was administered to 897 women age > 40
      years who lived in rural Robeson County in North Carolina. The sample consisted
      of three principal racial groups: whites, African Americans, and Native
      Americans. Survey comparisons were made among racial groups with respect to
      knowledge, attitudes, and behaviors regarding breast and cervical carcinoma
      screening. RESULTS: Overall, Native American and African-American women had lower
      levels of knowledge, more inaccurate beliefs, and more barriers to screening
      compared with white women. Among the notable findings were that 43% of the
      patient population did not mention mammograms and 53% did not mention Pap smears
      as breast and cervical carcinoma screening tests, respectively; furthermore,
      compared with white women, significantly fewer African-American and Native
      American women mentioned these tests (P < 0.001). Sixty-seven percent of all
      women reported that a physician had never encouraged them to receive a mammogram,
      although 75% reported having received a regular checkup in the preceding year.
      CONCLUSIONS: Although all low-income rural women experienced significant barriers
      to receiving cancer screening tests, these barriers were more common for minority
      women compared with white women. More research is needed to identify ways to
      overcome such barriers, especially among Native American women. The results of
      the current study have important implications with respect to the designing of
      interventions aimed at improving cancer screening for all women.

PMID- 15505785
TI  - Molego-based definition of the architecture and specificity of metal-binding
      sites.
AB  - Decomposing proteins into "molegos," building blocks that are conserved in
      sequence and 3D-structure, can identify functional elements. To demonstrate the
      specificity of the decomposition method, the PCPMer program suite was used to
      numerically define physical chemical property motifs corresponding to the molegos
      that make up the metal-containing active sites of three distinct enzyme families,
      from the dimetallic phosphatases, DNase 1 related nucleases/phosphatases, and
      dioxygenases. All three superfamilies bind metal ions in a beta-strand core
      region but differ in the number and type of ions needed for activity. The motifs
      were then used to automatically identify proteins in the ASTRAL40 database that
      contained similar motifs. The proteins with the highest PCPMer score in the
      database were primarily metal-binding enzymes that were related in function to
      those in the alignment used to generate the PCPMer motif lists. The proteins that
      contained motifs similar to the dioxygenases differed from those found with PCP
      motifs for phosphatases and nucleases. Relatively few metal-binding enzymes were
      detected when the search was done with PCP-motifs defined for interleukin-1
      related proteins, which have a beta-strand core but do not bind metal ions. While
      the box architecture was constant in each superfamily, the specificity for the
      metal ion preferred for enzymatic activity is determined by the pattern of
      carbonyl, hydroxyl or imadazole groups in key positions in the molegos. These
      results have implications for the design of metal-binding enzymes, and illustrate
      the ability of the PCPMer approach to distinguish, at the sequence level,
      structural and functional elements.

PMID- 15505786
TI  - Childhood-onset restless legs syndrome.
AB  - The clinical characteristics of childhood-onset restless legs syndrome are
      described. Thirty-two of 538 subjects (5.9%) examined in our sleep disorders
      center received diagnoses of restless legs syndrome. They were classified based
      on published criteria into probable (n = 9/32 or 28%) and definite (n = 23/32 or
      78%) categories. Apart from an earlier age of diagnosis of the probable group, no
      differences were found between the two categories. Sleep onset or sleep
      maintenance insomnia was the most common symptoms, being present in 28 of 32
      subjects (87.5%). Inattentiveness was seen in 8 of 32 subjects (25%). Serum
      ferritin levels were measured in 24 of 32 subjects and were below 50 microg/L in
      20 of 24 subjects (83%). A family history of restless legs syndrome was present
      in 23 of 32 (72%) subjects, with mothers almost three times more likely to be
      affected than fathers (p = 0.02). We conclude that iron deficiency and a strong
      family history are characteristic of childhood-onset restless legs syndrome.

PMID- 15505787
TI  - The ND1 gene of complex I is a mutational hot spot for Leber's hereditary optic
      neuropathy.
AB  - A novel mitochondrial DNA (mtDNA) transition (3733G-->A) inducing the E143 K
      amino acid change at a very conserved site of the NADH dehydrogenase subunit 1
      (ND1) was identified in a family with six maternally related individuals with
      Leber's hereditary optic neuropathy (LHON) and in an unrelated sporadic case, all
      negative for known mutations and presenting with the canonical phenotype. The
      transition was not detected in 1,082 control mtDNAs and was heteroplasmic in
      several individuals from both pedigrees. In addition, the mtDNAs of the two
      families were found to belong to different haplogroups (H and X), thus confirming
      that the 3733G-->A mutation occurred twice independently. Phosphorus magnetic
      resonance spectroscopy disclosed an in vivo brain and skeletal muscle energy
      metabolism deficit in the four examined patients. Muscle biopsy from two patients
      showed slight mitochondrial proliferation with abnormal mitochondria. Biochemical
      investigations in platelets showed partially insensitive complex I to rotenone
      inhibition. We conclude that the 3733G-->A transition is a novel cause of LHON
      and, after those at positions 3460 and 4171, is the third ND1 mutation to be
      identified in multiple unrelated families. This finding shows that, in addition
      to ND6, the ND1 subunit gene is also a mutational hot spot for LHON.

PMID- 15505789
TI  - Increased GABAergic function in mouse models of Huntington's disease: reversal by
      BDNF.
AB  - Huntington's disease (HD) is characterized by loss of striatal gamma-aminobutyric
      acid (GABA)ergic medium-sized spiny projection neurons (MSSNs), whereas some
      classes of striatal interneurons are relatively spared. Striatal interneurons
      provide most of the inhibitory synaptic input to MSSNs and use GABA as their
      neurotransmitter. We reported previously alterations in glutamatergic synaptic
      activity in the R6/2 and R6/1 mouse models of HD. In the present study, we used
      whole-cell voltage clamp recordings to examine GABAergic synaptic currents in
      MSSNs from striatal slices in these two mouse models compared to those in age
      matched control littermates. The frequency of spontaneous GABAergic synaptic
      currents was increased significantly in MSSNs from R6/2 transgenics starting
      around 5-7 weeks (when the overt behavioral phenotype begins) and continuing in 9
      14-week-old mice. A similar increase was observed in 12-15-month-old R6/1
      transgenics. Bath application of brain-derived neurotrophic factor, which is
      downregulated in HD, significantly reduced the frequency of spontaneous GABAergic
      synaptic currents in MSSNs from R6/2 but not control mice at 9-14 weeks.
      Increased GABA current densities also occurred in acutely isolated MSSNs from
      R6/2 animals. Immunofluorescence demonstrated increased expression of the
      ubiquitous alpha1 subunit of GABA(A) receptors in MSSNs from R6/2 animals. These
      results indicate that increases in spontaneous GABAergic synaptic currents and
      postsynaptic receptor function occur in parallel to progressive decreases in
      glutamatergic inputs to MSSNs. In conjunction, both changes will severely alter
      striatal outputs to target areas involved in the control of movement.

PMID- 15505791
TI  - MHC class I, beta2 microglobulin, and the INF-gamma receptor are upregulated in
      aged motoneurons.
AB  - During aging, spinal cord motoneurons show characteristic changes including the
      loss of afferent boutons, a selective process that associates with gliosis and
      behavioral motor impairment. Evidence suggests that the major histocompatibility
      complex Class I (MHC I) system may be involved in synaptic plasticity of neurons
      during development and regeneration. In search of a mechanism governing senescent
      changes in synaptic connectivity, we report evidence for increased expression of
      MHC I and beta2 microglobulin (beta2M) in motoneurons and glial-like profiles of
      30-month-old rats. The regulatory signal(s) for MHC I expression in normal
      neurons remains unresolved but among tentative molecules are cytokines such as
      interferon-gamma (INF-gamma) and tumor necrosis factor alpha (TNF-alpha).
      Interestingly, aged motoneurons, overlapping with those showing increased levels
      of MHC I, contained increased levels of INF-gamma receptor message. INF-gamma
      mRNA was detected at low levels in most (8/9) of the aged spinal cords but only
      infrequently (2/9) in young adult spinal cords; however, the cellular
      localization of INF-gamma mRNA could not be determined. Our data also indicates
      that TNF-alpha is upregulated in the senescent spinal cord but that TNF-alpha
      immunoreactive protein does not associate with motoneurons. We report evidence
      for an increased expression of MHC I and beta2M in senescent spinal motoneurons
      and discuss the possibility that this regulation associates with INF-gamma or
      changes in neurotrophin signaling and neuron activity in senescence.

PMID- 15505792
TI  - Expression of PDE5 splice variants during ontogenesis of chick dorsal root
      ganglia.
AB  - Cyclic GMP (cGMP)-binding cGMP-specific phosphodiesterase (PDE5) activity was
      found in chick dorsal root ganglia (DRG). PDE5 expression was studied at
      different stages of development: in embryonic day 10 (E10) and E18 embryos and in
      5-day post-hatching chick (P5). The presence of PDE5 was suggested by the ion
      exchange chromatography elution profile in E18 DRG extracts, where cGMP-specific
      hydrolytic calmodulin-independent activity was found; in other stages, this
      activity coeluted with the PDE1 calmodulin-stimulated isoform characterized
      previously. Inhibition studies supported the hypothesis that the newly identified
      PDE activity belongs to the PDE5 isoform. Western blot analysis using a PDE5
      specific antibody was also carried out and revealed the presence of three
      specific immunoreactive bands with apparent molecular weights of 98, 93, and 86
      kDa, corresponding to the three described splice variants (PDE5A1, PDE5A2, and
      PDE5A3). The expression in DRG of the three PDE5 isoforms was also confirmed by
      RT-PCR. Developmental regulation of PDE5 was revealed by the immunoblot analysis
      at different stages; expression was very low at E10 but an overall substantial
      increase occurred between E10-18 (about 12-fold, considering the three PDE5
      isoforms together). Differences were revealed, however, when a single PDE5
      isoform was considered. PDE5A1 and PDE5A3 showed an increase at all stages
      although more pronounced between E10-18, whereas PDE5A2 underwent a marked
      increase (about 38-fold) in the first period and remained nearly constant between
      E18 and P5. This is the first evidence of PDE5 in sensory neurons, and the
      distinct temporal expression patterns of enzyme isoforms may indicate different
      physiologic roles in developing and mature chick DRG.

PMID- 15505793
TI  - Neurospheres: insights into neural stem cell biology.
AB  - Neural stem cells (NSC) are a tissue-specific subtype of self-renewing and
      multipotent cells that can give rise to all neural populations. In this review,
      the importance of maintaining cell-cell contacts in the study of NSC is
      highlighted, and data obtained from some crucial single-cell studies is compared
      to results obtained from neurospheres, where aggregates of NSC are grown in
      suspension. In particular, results that indicate how this culture system may be
      well suited to analyze NSC plasticity, cell-cell, and cell-extracellular matrix
      (ECM) interactions are pointed out, and the hypothesis that cell-cell and cell
      ECM contacts may be essential for NSC maintenance, survival, and proliferation is
      highlighted. Finally, it is suggested that neurospheres might play a role in the
      study of context-dependent behavior of NSC in niches by providing a system where
      NSC can be challenged chemically or biologically and analyzed in vitro, in a time
      and context-dependent manner.

PMID- 15505794
TI  - Pregnenolone sulfate enhances long-term potentiation in CA1 in rat hippocampus
      slices through the modulation of N-methyl-D-aspartate receptors.
AB  - Among the different steroids found in the brain, pregnenolone sulfate (3beta
      hydroxy-5-pregnen-20-one-3-sulfate; PREGS) is known to enhance hippocampal
      associated memory. The present study employs rat hippocampal slices to
      investigate the ability of PREGS to modulate long-term potentiation (LTP), a
      phenomenon considered as a model of synaptic plasticity related to memory
      processes. LTP (3 x 100 Hz/1 sec within 2 min), implicated essentially
      glutamatergic transmission, for which the different synaptic events could be
      pharmacologically dissociated. We show that PREGS enhances LTP in CA1 pyramidal
      neurons at nanomolar concentrations and exhibits a bell-shaped concentration
      response curve. The maximal effect of PREGS on both induction and maintenance
      phases of LTP is observed at 300 nM and requires 10 min of superfusion. Although
      PREGS does not change the N-methyl-D-aspartate (NMDA) component of the field
      potentials (fEPSPs) isolated in the presence of 10 microM 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX) in Mg2+-free artificial cerebrospinal fluid,
      PREGS does enhance the response induced by NMDA application (50 microM, 20 sec).
      PREGS does not modify the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid (AMPA) component of the fEPSPs isolated in the presence of 100 microM DL-2
      amino-7-phosphopentanoic acid (DL-AP5) or its potentiation induced by a single
      tetanic stimulation and the response induced by AMPA application (10 microM, 10
      sec). Furthermore, PREGS does not affect the recurrent inhibition of the fEPSPs
      mediated by gamma-aminobutyric acid type A (GABA(A)) receptor. In conclusion,
      this study shows the ability of PREGS to enhance LTP in CA1 by accentuating the
      activity of NMDA receptors. This modulation of LTP might mediate the steroid
      induced enhancement of memory.

PMID- 15505795
TI  - Diurnal cycle in salivary cortisol levels in common marmosets.
AB  - A noninvasive method of saliva sampling was used to assess the diurnal cortisol
      rhythm from 0900 to 1700 hr in the common marmoset (Callithrix jacchus). The
      levels of cortisol were highest in the morning and declined significantly over
      the day. Individual marmosets varied in the magnitude of the cycle, and the
      greatest individual variability occurred in the morning levels. The decrease in
      cortisol levels was more rapid after than before the midday feeding period in
      subordinate marmosets (aged 53-63 months) compared to dominant marmosets (aged 79
      80 months), and overall, the levels of cortisol were higher in the subordinate
      marmosets. We found no effect of sex on cortisol levels across the cycle.

PMID- 15505796
TI  - Maternal separation alters maternal care, but has minor effects on behavior and
      brain opioid peptides in adult offspring.
AB  - The aim of the study was to investigate the effect of repeated maternal
      separation (MS; 4 hr per day) during postnatal Days 1 to 15 on emotionality and
      voluntary ethanol intake in adult male and female Wistar rat offspring relative
      to controls exposed to a brief (5-min) daily handling procedure. Brain
      immunoreactive opioid peptide levels and plasma levels of corticosterone also
      were measured. There were mainly no alterations in any of the tested behaviors
      (i.e., fleeing and freezing responses, exploratory behavior, spontaneous and
      amphetamine-induced locomotor activity and competitive behavior), ethanol intake,
      or immunoreactive opioid peptide levels in MS offspring, either in males or
      females, compared to their respective controls nor were there any differences in
      plasma corticosterone between groups. In addition, the dams' retrieval behavior
      of the pups also was studied, showing that MS dams spent more time in the nest
      with the pups after the 4-hr separation period compared to control dams. With
      respect to the used protocol of the MS procedure in the present study, our
      results do not provide support for the suggestion that this procedure is a
      relevant model for studying development of psychopathology and vulnerability to
      drug abuse.

PMID- 15505797
TI  - Rewarding properties of social interactions in adolescent and adult male and
      female rats: impact of social versus isolate housing of subjects and partners.
AB  - Social interactions have been shown to be rewarding for adolescent and adult
      rats; however, there has been little emphasis on comparing the strength of the
      rewarding value of social stimuli across ontogeny. Since age differences in
      social interactions may vary with sex or housing circumstances, the present study
      assessed social conditioned place preference (CPP) in adolescent and adult male
      and female Sprague-Dawley rats housed either socially or in isolation and
      conditioned with either group-housed or isolate-housed partners. Isolated animals
      of both sexes and ages demonstrated social CPP, with the strongest preference
      emerging in adolescent males. Social CPP was not evident in group-housed adults
      whereas group-housed adolescents developed a preference for the compartment
      previously paired with similarly housed partners; however, when socially housed
      adolescents were conditioned with isolated partners, social CPP did not emerge.
      Age differences in social CPP may reflect age-related neural alterations in brain
      systems implicated in regulation of social behavior.

PMID- 15505798
TI  - Prehatch entrainment of circadian rhythms in the domestic chick using different
      light regimes.
AB  - The onset of circadian rhythms in many animals occurs during prenatal
      development. We conducted four experiments, using the domestic chick as a model,
      to assess when these rhythms can first be entrained and the type of light
      zeitgeber necessary. In Experiment 1, the presence of circadian rhythms was
      assessed using tonic immobility, an antipredator behavior, whereas in Experiments
      2 to 4 body temperature was studied. We demonstrate that (a) circadian rhythms
      can be entrained during the late stage of the chick's 21-day incubation period
      (prehatch Days 13-18), (b) only 1 day of light cues [12:12 hr light:dark
      (12L:12D)] on prehatch Day 13 is necessary for entrainment, and (c) short bouts
      of light, which simulate the light cues embryos typically experience during
      natural incubation, can act as zeitgebers although they are not as effective as
      12L:12D. The onset of entrainment is earlier than predicted and suggests that the
      brain structures mediating circadian rhythms mature sooner than proposed by
      previous research.

PMID- 15505799
TI  - Cardiac vagal regulation across the preschool period: stability, continuity, and
      implications for childhood adjustment.
AB  - Stability and continuity of vagal regulation of the heart, operationalized as
      suppression of respiratory sinus arrhythmia (RSA) during challenge, was examined
      in a longitudinal study of preschoolers. A sample of 154 two-year-old children
      was recruited for participation in a study of the effects of emotional and
      behavioral challenge on cardiac activity and behavioral indices of adjustment and
      self-regulation. A total of 122 of these children were assessed again at age 4.5
      years. At both ages, the children were assessed in a series of laboratory
      procedures that were intended to be emotionally and behaviorally challenging,
      during which time heart rate was recorded. To assess vagal regulation, resting
      measures of RSA and RSA suppression to the challenge task were derived from these
      procedures. To assess childhood adjustment and self-regulation, a number of
      parent-report measures were administered when the children were 4.5 years of age.
      Results indicated that there was high stability in RSA suppression across the
      challenge tasks within both ages, modest cross-age stability in RSA suppression,
      and a significant decrease in the magnitude of RSA suppression across age.
      Second, children who displayed a pattern of stable and high suppression across
      the preschool period were less emotionally negative, and had fewer behavior
      problems and better social skills than other children.

PMID- 15505800
TI  - Physiological and neuropsychological correlates of approach/withdrawal tendencies
      in preschool: further examination of the behavioral inhibition system/behavioral
      activation system scales for young children.
AB  - This study examined a parent-report version of the Behavioral Inhibition
      System/Behavioral Activation System (BIS/BAS) scales, a measure of approach
      withdrawal motivation, in 170 children between the ages of 3 to 5 years attending
      Head Start programs. Physiological measures included assessments of baseline
      salivary cortisol and change in cortisol in response to the assessment session,
      and resting and suppression estimates of cardiac vagal tone. Cognitive self
      regulation was assessed with a peg-tapping measure of inhibitory control and an
      item-selection measure of cognitive set-shifting ability. Results indicated that
      higher level of parent-reported withdrawal motivation was associated with
      cortisol increase and that parent-reported approach motivation tended to be
      associated with cortisol decrease across the assessment session. Higher level of
      parent-reported withdrawal also was positively related to cognitive self
      regulation while parent-reported approach was negatively related to cognitive
      self-regulation. Person-oriented analysis indicated that children characterized
      by both high level of approach and high level of withdrawal tended to exhibit
      lower resting vagal tone, higher initial cortisol, and minimal cortisol and vagal
      change. Overall, findings suggest that the parent-report version of the BIS/BAS
      scales works well as an indicator of children's reactivity to appetitive and
      aversive motivational stimuli. Directions for future research and implications of
      findings for the longitudinal study of temperament and personality are discussed.

PMID- 15505801
TI  - Developmental changes in baseline cortisol activity in early childhood: relations
      with napping and effortful control.
AB  - Development of the hypothalamic-pituitary-adrenocortical (HPA) axis was examined
      using salivary cortisol levels assessed at wake-up, midmorning, midafternoon, and
      bedtime in 77 children aged 12, 18, 24, 30, and 36 months, in a cross-sectional
      design. Hierarchical linear modeling (HLM) analyses were used to characterize
      cortisol production across the day and to examine age-related differences. Using
      area(s) under the curve (AUC), cortisol levels were higher among the 12-, 18-,
      and 24-month children than among the 30- and 36-month children. For all five age
      groups, cortisol levels were highest at wake-up and lowest at bedtime.
      Significant decreases were noted between wake-up and midmorning, and between
      midafternoon and bedtime. Unlike adults, midafternoon cortisol levels were not
      significantly lower than midmorning levels. Over this age period, children napped
      less and scored increasingly higher on parent reports of effortful control. Among
      the 30- and 36-month children, shorter naps were associated with more adultlike
      decreases in cortisol levels from midmorning to midafternoon. Considering all of
      the age groups together, effortful control correlated negatively with cortisol
      levels after controlling for age. These results suggest that circadian regulation
      of the HPA axis continues to mature into the third year in humans, and that its
      maturation corresponds to aspects of behavioral development.

PMID- 15505802
TI  - A full belly and colostrum: two major determinants of filial love.
AB  - The establishment of filial bonding in sheep relies on the success of the first
      suckling bouts. Previous work has shown that colostrum ingestion facilitates the
      development of a preference for the mother. We conducted a series of experiments
      to investigate the influence of quantitative and qualitative factors linked to
      fluid ingestion. The first experiment demonstrated that the procedure was not
      detrimental to the mother-young interaction and did not cause any harm to the
      lamb. In a second experiment, lambs could interact with their dam, but were
      deprived of suckling during the first 12 hr after birth (The udder was covered.)
      and fed via a nasogastric tube in the presence of their mother on seven
      occasions. When tested in a two-choice test at 12 hr of age, lambs that received
      either colostrum or saline (total amount = 10% birth weight) spent more time near
      their own dam than near an alien ewe. When smaller volumes of fluids were used
      (5% birth weight), lambs that received colostrum showed a preference for their
      mother while those ingesting saline did not. The differences persisted at 24 hr
      even though all the lambs had access to the maternal udder from 12 hr onward, and
      these differences were not related to weight variations or body temperature. In
      the choice test, the motor skills and vocal activity of the lambs were not
      affected by the treatment nor were the behaviors of the ewes. The third
      experiment showed that colostrum, and saline to a lesser extent, reduces the
      number of vocalizations emitted by lambs compared to sham-intubated lambs, but
      did not otherwise influence mother-young interactions. This suggests that post
      ingestive factors may facilitate the development of mother preference through a
      satiated or comforted state. This is the first evidence that depending on the
      amount of liquids ingested, a preferential relationship with the mother can be
      established via nutritional and nonnutritional signals originating from the
      gastrointestinal region, pointing out the major role played by the gut-brain axis
      in the development of filial bonding.

PMID- 15505803
TI  - Computational studies and peptidomimetic design for the human p53-MDM2 complex.
AB  - The interaction between human p53 and MDM2 is a key event in controlling cell
      growth. Many studies have suggested that a p53 mimic would be sufficient to
      inhibit MDM2 to reduce cell growth in cancerous tissue. In order to design a
      potent p53 mimic, molecular dynamics (MD) simulations were used to examine the
      binding interface and the effect of mutating key residues in the human p53-MDM2
      complex. The Generalized Born surface area (GBSA) method was used to estimate
      free energies of binding, and a computational alanine-scanning approach was used
      to calculate the relative effects in the free energy of binding for key
      mutations. Our calculations determine the free energy of binding for a model p53
      MDM2 complex to be -7.4 kcal/mol, which is in very good agreement with the
      experimentally determined values (-6.6--8.8 kcal/mol). The alanine-scanning
      results are in good agreement with experimental data and calculations by other
      groups. We have used the information from our studies of human p53-MDM2 to design
      a beta-peptide mimic of p53. MD simulations of the mimic bound to MDM2 estimate a
      free energy of binding of -8.8 kcal/mol. We have also applied alanine scanning to
      the mimic-MDM2 complex and reveal which mutations are most likely to alter the
      binding affinity, possibly giving rise to escape mutants. The mimic was compared
      to nutlins, a new class of inhibitors that block the formation of the p53-MDM2
      complex. There are interesting similarities between the nutlins and our mimic,
      and the differences point to ways that both inhibitors may be improved. Finally,
      an additional hydrophobic pocket is noted in the interior of MDM2. It may be
      possible to design new inhibitors to take advantage of that pocket.

PMID- 15505804
TI  - Gene expression analysis in the hippocampal formation of tree shrews chronically
      treated with cortisol.
AB  - Adrenal corticosteroids influence the function of the hippocampus, the brain
      structure in which the highest expression of glucocorticoid receptors is found.
      Chronic high levels of cortisol elicited by stress or through exogenous
      administration can cause irreversible damage and cognitive deficits. In this
      study, we searched for genes expressed in the hippocampal formation after chronic
      cortisol treatment in male tree shrews. Animals were treated orally with cortisol
      for 28 days. At the end of the experiments, we generated two subtractive
      hippocampal hybridization libraries from which we sequenced 2,246 expressed
      sequenced tags (ESTs) potentially regulated by cortisol. To validate this
      approach further, we selected some of the candidate clones to measure mRNA
      expression levels in hippocampus using real-time PCR. We found that 66% of the
      sequences tested (10 of 15) were differentially represented between cortisol
      treated and control animals. The complete set of clones was subjected to a
      bioinformatic analysis, which allowed classification of the ESTs into four
      different main categories: 1) known proteins or genes (approximately 28%), 2)
      ESTs previously published in the database (approximately 16%), 3) novel ESTs
      matching only the reference human or mouse genome (approximately 5%), and 4)
      sequences that do not match any public database (50%). Interestingly, the last
      category was the most abundant. Hybridization assays revealed that several of
      these clones are indeed expressed in hippocampal tissue from tree shrew, human,
      and/or rat. Therefore, we discovered an extensive inventory of new molecular
      targets in the hippocampus that serves as a reference for hippocampal
      transcriptional responses under various conditions. Finally, a detailed analysis
      of the genomic localization in human and mouse genomes revealed a survey of
      putative novel splicing variants for several genes of the nervous system.

PMID- 15505805
TI  - ADAM23 is a cell-surface glycoprotein expressed by central nervous system
      neurons.
AB  - Several members of the ADAM (a disintegrin and metalloprotease) family of
      proteins have been implicated in biological processes ranging from fertilization
      to myoblast fusion and neural cell fate determination. These proteins have so far
      been studied mostly in terms of their protease activity, but a considerable
      amount of evidence suggests that many ADAMs are also important as receptors for
      cell-surface integrins. We have shown that, for one such member of the family,
      ADAM23, mRNA transcripts are expressed in neuronal cells throughout the rat
      brain, at all stages of postnatal development, and that particularly high
      transcript concentrations are found in the hippocampus and cerebellum. Using an
      antibody that we raised against the rat ADAM23 disintegrin domain, we found that
      ADAM23 is present at detectable levels only in nervous system tissue. Our
      analysis of ADAM23 expression in cultured cerebellar granule cells (CGCs)
      furthermore suggested that this protein is synthesized as a glycosylated
      precursor of about 100 kD whose maturation depends on cleavage by furin or a
      related enzyme. We have also shown ADAM23 to be expressed primarily as a cell
      surface protein that appears to be localized to sites of intercellular contact.
      Taken together, these data are consistent with a model wherein ADAM23 serves to
      mediate cell-cell interactions within the mammalian CNS.

PMID- 15505806
TI  - Utilization of juvenile animal studies to determine the human effects and risks
      of environmental toxicants during postnatal developmental stages.
AB  - BACKGROUND: Toxicology studies utilizing animals and in vitro cellular or tissue
      preparations have been used to study the toxic effects and mechanism of action of
      drugs and chemicals and to determine the effective and safe dose of drugs in
      humans and the risk of toxicity from chemical exposures. Testing in animals could
      be improved if animal dosing using the mg/kg basis was abandoned and drugs and
      chemicals were administered to compare the effects of pharmacokinetically and
      toxicokinetically equivalent serum levels in the animal model and human. Because
      alert physicians or epidemiology studies, not animal studies, have discovered
      most human teratogens and toxicities in children, animal studies play a minor
      role in discovering teratogens and agents that are deleterious to infants and
      children. In vitro studies play even a less important role, although they are
      helpful in describing the cellular or tissue effects of the drugs or chemicals
      and their mechanism of action. One cannot determine the magnitude of human risks
      from in vitro studies when they are the only source of toxicology data. METHODS:
      Toxicology studies on adult animals is carried out by pharmaceutical companies,
      chemical companies, the Food and Drug Administration (FDA), many laboratories at
      the National Institutes of Health, and scientific investigators in laboratories
      throughout the world. Although there is a vast amount of animal toxicology
      studies carried out on pregnant animals and adult animals, there is a paucity of
      animal studies utilizing newborn, infant, and juvenile animals. This deficiency
      is compounded by the fact that there are very few toxicology studies carried out
      in children. That is one reason why pregnant women and children are referred to
      as "therapeutic orphans." RESULTS: When animal studies are carried out with
      newborn and developing animals, the results demonstrate that generalizations are
      less applicable and less predictable than the toxicology studies in pregnant
      animals. Although many studies show that infants and developing animals may have
      difficulty in metabolizing drugs and are more vulnerable to the toxic effects of
      environmental chemicals, there are exceptions that indicate that infants and
      developing animals may be less vulnerable and more resilient to some drugs and
      chemicals. In other words, the generalization indicating that developing animals
      are always more sensitive to environmental toxicants is not valid. For animal
      toxicology studies to be useful, animal studies have to utilize modern concepts
      of pharmacokinetics and toxicokinetics, as well as "mechanism of action" (MOA)
      studies to determine whether animal data can be utilized for determining human
      risk. One example is the inability to determine carcinogenic risks in humans for
      some drugs and chemicals that produce tumors in rodents, When the oncogenesis is
      the result of peroxisome proliferation, a reaction that is of diminished
      importance in humans. CONCLUSIONS: Scientists can utilize animal studies to study
      the toxicokinetic and toxicodynamic aspects of drugs and environmental toxicants.
      But they have to be carried out with the most modern techniques and interpreted
      with the highest level of scholarship and objectivity. Threshold exposures, no
      adverse-effect level (NOAEL) exposures, and toxic effects can be determined in
      animals, but have to be interpreted with caution when applying them to the human.
      Adult problems in growth, endocrine dysfunction, neurobehavioral abnormalities,
      and oncogenesis may be related to exposures to drugs, chemicals, and physical
      agents during development and may be fruitful areas for investigation. Maximum
      permissible exposures have to be based on data, not on generalizations that are
      applied to all drugs and chemicals. Epidemiology studies are still the best
      methodology for determining the human risk and the effects of environmental
      toxicants. Carrying out these focused studies in developing humans will be
      difficult. Animal studies may be our only alternative for answering many
      questions with regard to specific postnatal developmental vulnerabilities.

PMID- 15505807
TI  - Detection of tissue-specific effects by methotrexate on differentiating mouse
      embryonic stem cells.
AB  - BACKGROUND: Pluripotent embryonic stem (ES) cells offer a unique possibility to
      monitor the differentiation of several cell types in vitro. This study attempts
      to identify marker genes during in vitro cell differentiation of murine ES cells
      and allow a prediction of chemical effects on cell differentiation of specific
      target tissues. The study focused on the expression pattern of key genes involved
      in cardiomyocyte and osteoblast differentiation: Oct-4, Brachyury, Nkx2.5, alpha
      myosin heavy chain, Cbfa1, and Osteocalcin. METHODS: Methotrexate was selected
      due to its well-characterized teratogenic effects. Several in vivo studies have
      demonstrated the specific interactions of methotrexate with bone formation
      whereas the cardiovascular system is not specifically affected after exposure to
      low concentration. The capability of murine ES cells to differentiate in vitro
      into cardiomyocytes as well as into osteoblasts have been used to demonstrate the
      target cell specificity in vitro, at non-cytotoxic concentration. RESULTS:
      Exposure of differentiating ES cells did not result in any gene profile
      modification of the selected cardiomyocyte specific genes, whereas the expression
      of osteoblast specific key genes, Cbfa1 and Osteocalcin, decreased. At the latter
      stages of skeletal differentiation we observed a 30% decrease in gene expression
      for Cbfa1 and a 60% decrease for Osteocalcin, with reference to the control.
      Early marker genes for undifferentiated cells and mesodermal cells were not
      modified after methotrexate treatment. CONCLUSIONS: These results show the
      possibility to integrate specific in vitro tests for teratogenicity in a test
      strategy for developmental toxicity.

PMID- 15505808
TI  - Developmental toxicity evaluation of ibuprofen and tolmetin administered in
      triple daily doses to Wistar CRL:(WI)WUBR rats.
AB  - BACKGROUND: Ibuprofen and tolmetin are popular non-steroidal anti-inflammatory
      drugs. Previous animal studies taken with single daily doses showed their good
      prenatal tolerability. However, since both cyclooxygenase (COX) inhibitors have a
      short half-life, the current report presents drug developmental effects after
      triple daily doses administration, as they are used in human. METHODS: Drugs were
      separately, orally dosed to pregnant rats triple daily 8 hr apart from day 8 to
      21 (GD=1-plug day). The total daily doses were set at 25.5, 255.0, and 600.0
      mg/kg for ibuprofen and 25.5, 255.0, and 2550.0 mg/kg for tolmetin. Fetuses were
      delivered on GD 21 and routinely examined. Comprehensive clinical and
      developmental measurements were done. RESULTS: Maternal toxicity and intrauterine
      growth retardation were found in groups exposed to the highest doses of both
      drugs. An increase of external variations was reported in groups exposed to the
      middle and highest dose of ibuprofen and to the highest dose of tolmetin.
      Skeletal variations were significantly different only in litters treated with the
      highest doses of the drugs. Pooled statistical analysis showed a higher incidence
      of midline and ventricular septal (VSD) defect in rat fetuses exposed to COX
      inhibitors when compared with historical control data. For ibuprofen, the
      influence on VSD was similar to aspirin. CONCLUSION: Both COX inhibitors were
      toxic to dams in the highest doses evaluated, which caused a significantly
      greater incidence of intrauterine growth retardation and developmental
      variations.

PMID- 15505809
TI  - The tail of myosin reduces actin filament velocity in the in vitro motility
      assay.
AB  - It has been observed that heavy meromyosin (HMM) propels actin filaments to
      higher velocities than native myosin in the in vitro motility assay, yet the
      reason for this difference has remained unexplained. Since the major difference
      between these two proteins is the presence of the tail in native myosin, we
      tested the hypothesis that unknown interactions between actin and the tail (LMM)
      slow motility in native myosin. Chymotryptic HMM and LMM were mixed in a range of
      molar ratios (0-5 LMM/HMM) and compared to native rat skeletal myosin in the in
      vitro motility assay at 30 degrees C. Increasing proportions of LMM to HMM slowed
      actin filament velocities, becoming equivalent to native myosin at a ratio of 3
      LMM/HMM. NH4+ -ATPase assays demonstrated that HMM concentrations on the surface
      were constant and independent of LMM concentration, arguing against a simple
      displacement mechanism. Relationships between velocity and the number of
      available heads suggested that the duty cycle of HMM was not altered by the
      presence of LMM. HMM prepared with a lower chymotrypsin concentration and with
      very short digestion times moved actin at the same high velocity. The difference
      between velocities of actin filament propelled by HMM and HMM/LMM decreased with
      increasing ionic strength, suggesting that ionic bonds between myosin tail and
      actin filaments may play a role in slowing filament velocity. These data suggest
      the high velocities of actin filaments over HMM result from the absence of drag
      generated by the myosin tail, and not from proteolytic nicking of the motor
      domain.

PMID- 15505810
TI  - Endohedral zintl ions: intermetalloid clusters.
AB  - Tetrels can be regarded as most promising candidates for the construction of
      larger clusters. Recent examples have shown that larger clusters are particularly
      stable if they contain interstitial atoms (e.g. [Pt@Pb12]2-). Many salts of the
      polyhedral anions are soluble, but a number of examples-usually those with higher
      charges-occur only as quasi-discrete units in saltlike crystals (Zintl phases) or
      as building blocks in intermetallic phases. In this Minireview, the chemistry of
      intermetalloid clusters is reviewed with reference to the endohedral Zintl ions,
      Zintl phases, and polyhedral building blocks of intermetallic compounds,
      including heteroatomic species in the gas phase. We focus on selected examples
      and discuss the new findings in the context of recent advances in the field of
      metalloid clusters and (endohedral) fullerenes and fullerides.

PMID- 15505811
TI  - Loop flexibility and solvent dynamics as determinants for the selective
      inhibition of cyclin-dependent kinase 4: comparative molecular dynamics
      simulation studies of CDK2 and CDK4.
AB  - The design and discovery of selective cyclin-dependent kinase 4 (CDK4) inhibitors
      have been actively pursued in order to develop therapeutic cancer treatments. By
      means of a consecutive computational protocol involving homology modeling,
      docking experiments, and molecular dynamics simulations, we examine the
      characteristic structural and dynamic properties that distinguish CDK4 from CDK2
      in its complexation with selective inhibitors. The results for all three CDK4
      selective inhibitors under investigation show that the large-amplitude motion of
      a disordered loop of CDK4 is damped out in the presence of the inhibitors whereas
      their binding in the CDK2 active site has little effect on the loop flexibility.
      It is also found that the binding preference of CDK4- selective inhibitors for
      CDK4 over CDK2 stems from the reduced solvent accessibility in the active site of
      the former due to the formation of a stable hydrogen-bond triad by the Asp99,
      Arg101, and Thr102 side chains at the top of the active-site gorge. Besides the
      differences in loop flexibility and solvent accessibility, the dynamic
      stabilities of the hydrogen bonds between the inhibitors and the side chain of
      the lysine residue at the bottom of the active site also correlate well with the
      relative binding affinities of the inhibitors for the two CDKs. These results
      highlight the usefulness of this computational approach in evaluating the
      selectivity of a CDK inhibitor, and demonstrate the necessity of considering
      protein flexibility and solvent effects in designing new selective CDK4-selective
      inhibitors.

PMID- 15505812
TI  - Complete assignment of 1H and 13C NMR spectra of some 4'-substituted diethyl 1
      methylthio- and diethyl 1-methylsulfonyl-2-oxo-2-phenylethylphosphonates.
AB  - The complete assignment of 1H and 13C NMR spectra of some 4'-substituted diethyl
      1-methylthio- and diethyl 1-methylsulfonyl-2-oxo-2-phenylethylphosphonates
      bearing as substituents methoxy, fluoro, chloro, bromo and nitro is reported.

PMID- 15505813
TI  - Conformation of drawn poly(trimethylene terephthalate) studied by solid-state 13C
      NMR.
AB  - The change in the conformation of the flexible O-CH2-CH2-CH2-O segment of
      poly(trimethylene terephthalate) (PTT) monofilament caused by drawing was
      investigated by means of the gamma-gauche effect on the 13C solid-state NMR
      chemical shift of the internal methylene carbon, combined with the NMR
      relaxations. The conformation around the O-CH2 and CH2-O bonds for as-spun fiber
      was trans/trans. On drawing, followed by heat treatment, the conformation changed
      to gauche/gauche. The ratio of gauche/gauche to trans/trans for the drawn PTT
      fiber was determined quantitatively.

PMID- 15505814
TI  - Investigation of the association and flexibility of cationic lipidic peptide
      dendrons by NMR spectroscopy.
AB  - The cationic peptide dendrons synthesized and studied are lower generation
      polylysine-based partial dendrimers with or without lipid chains in the core. The
      dendrons with lipidic chains can be utilized as protein and liposomal mimics
      because of their unique structural properties. The full assignments of three
      different dendrons (L)7(NH2)8, (C14)1(L)7(NH2)8 and (C14)3(L)7(NH2)8 were
      obtained in D2O and H2O/D2O using a 500 MHz NMR spectrometer. The hydrophobic
      lipidic core of branched polylysine dendrons was found to induce aggregation upon
      increasing concentration. Because non-lipidic dendrons do not self-assemble, the
      behaviour and internal structural features of two different dendrons with one and
      three C14 hydrocarbon chains were explored. The critical association
      concentration clearly depends on the number of core hydrophobic residues and the
      association starts at 0.025 mM for (C14)1(L)7(NH2)8 and 0.05 mM for
      (C14)3(L(7(NH2)8. Chemical shift analysis also revealed that the hydrophobic
      chains of the dendrons associate in the core, whereas the polar head groups (NH2)
      are mainly located at the surfaces of the aggregates. The T1 relaxation time
      measurements showed that the mobility of the hydrocarbon chain is greater with
      the monomeric form of dendron (C14)1(L)7(NH2)8) than that of monomer
      (C14)3(L)7(NH2)8. The inter-chain hydrophobic interactions restrict the
      flexibility of the dendron with three hydrocarbon chains. As expected, the
      flexibility of the monomeric form is higher than that of the aggregated state for
      both of the dendrons.

PMID- 15505815
TI  - An intramolecular ionic hydrogen bond stabilizes a cis amide bond rotamer of a
      ring-opened rapamycin-degradation product.
AB  - Rapamycin (1), a macrolide immunosuppressant, undergoes degradation into ring
      opened acid products 2 and 3 under physiologically relevant conditions. The
      unsaturated product (3) was isolated and studied in this work. Unlike 1, which
      has its amide primarily in a trans conformation in solution, 3 has both cis and
      trans conformations in approximately a 1:1 ratio in dimethyl sulfoxide (DMSO).
      The amount of cis rotamer was increased dramatically in the presence of an
      organic base such as triethylamine. The detailed NMR results indicate that the
      cis rotamer is stabilized through an intramolecular ionic hydrogen bond of the
      carboxylate anion with the tertiary alcohol as part of a nine-membered ring
      system. This hydrogen bond was characterized further in organic media and the
      trans-cis rotamer equilibria were used to estimate the relative bond strengths in
      several solvents. The additional stabilization arising from this ionic hydrogen
      bond in the cis rotamer was determined to be 1.4 kcal mol(-1) in DMSO-d6, 2.0
      kcal mol(-1) in CD3CN and 1.1 kcal mol(-1) in CD3OD.

PMID- 15505816
TI  - The short-term effect of nifedipine tocolysis on placental, fetal cerebral and
      atrioventricular Doppler waveforms.
AB  - OBJECTIVE: To evaluate the effect of nifedipine on placental and fetal middle
      cerebral and atrioventricular Doppler waveforms. METHODS: Doppler waveforms of
      uterine (UtA), umbilical (UA) and middle cerebral (MCA) arteries and both
      atrioventricular valves were measured from 21 pregnant women/fetuses prior to and
      during nifedipine therapy for preterm labor. Maternal and fetal heart rates
      (FHR), maternal systolic and diastolic blood pressure, the Doppler pulsatility
      index and systolic/diastolic ratio of the UtA, UA and MCA were measured. The
      total time velocity integrals (TVI) of tricuspid and mitral valves and their E
      wave/A-wave (E/A) TVI ratios were measured. Wilcoxon signed pairs test was used
      to compare the differences in Doppler parameters before and at 3 h after
      nifedipine loading up to a maximum dose of 40 mg. RESULTS: Fetal arterial and UtA
      Doppler parameters were not different before and after nifedipine therapy. Blood
      flow across the atrioventricular valves and the TVI were equally unaffected by
      nifedipine. The TVI x FHR product was also unchanged following nifedipine
      therapy. CONCLUSIONS: In women with otherwise uncomplicated pregnancies,
      nifedipine loading and tocolysis are generally well tolerated by the mother.
      Placental and fetal cerebral arterial blood flow, fetal systolic and diastolic
      cardiac function and downstream distribution of fetal cardiac output are
      unaffected by nifedipine loading. These results apply to women with unchanged
      vital parameters. Further studies are necessary to show long-term effects of
      nifedipine therapy and may help to refine choice of tocolytic agents.

PMID- 15505817
TI  - Measuring engagement of the fetal head: validity and reproducibility of a new
      ultrasound technique.
AB  - OBJECTIVE: Fetal head engagement can be assessed by translabial ultrasound and
      has been shown to be predictive of delivery mode. We attempted to validate the
      technique by comparing ultrasound with abdominal and vaginal palpation.
      Reproducibility was tested in a blinded test-retest series. METHODS: In a
      prospective clinical study, 139 nulliparous women between 35 + 3 and 40 + 4
      weeks' gestation were assessed by translabial ultrasound, abdominal palpation of
      the fetal head (n = 139) and vaginal examination (n = 112). Ultrasound was
      performed using two methods, with the symphysis pubis as reference. A test-retest
      series was performed in 90 women. RESULTS: Ultrasound of head engagement
      correlated strongly with abdominal palpation, full Bishop scores and vaginal
      assessment (all P < 0.001 for Kendall's tau-b). Intraclass correlation
      coefficients (n = 90) for the two methods were 0.75 and 0.92, signifying
      excellent interobserver agreement. Reproducibility was higher for the method
      using the central symphyseal axis as reference. CONCLUSION: Quantitation of head
      engagement by translabial ultrasound is highly reproducible and correlates
      strongly with clinical measures of head engagement. We are now undertaking a
      prospective study to assess the predictive value of this new parameter for
      intrapartum events.

PMID- 15505818
TI  - NMR assignments and single-crystal X-ray diffraction analysis of deoxyloganic
      acid.
AB  - 7-Deoxyloganic acid (1), citrusin C (2), 3,4-dihydroxyl benzoic acid (3) and (E)
      caffeic acid (4) were isolated from the water-soluble fraction of ethanol
      extracts of Morina nepalensis var. alba Hand.-Mazz. and their structures were
      determined on the basis of spectroscopic evidence. The total assignments of 1H
      and 13C NMR spectra of 1 in solvents CD3OD, D2O and CDCl3 were reported, in
      addition to the single-crystal X-ray diffraction analysis of its tetraacetate 1a.
      All compounds were obtained from Morina genus for the first time.

PMID- 15505819
TI  - Structural and spectral assignment by two-dimensional NMR of two new derivatives
      of the abietane diterpenoid taxodione.
AB  - Two new abietane derivatives were obtained by treatment of the diterpene
      taxodione with diazomethane. Their structures were determined by mass
      spectrometry and NMR studies, including one- and two-dimensional experiments.

PMID- 15505820
TI  - DOSY of sample-limited mixtures: comparison of cold, nano and conventional
      probes.
AB  - The DOSY analysis of dilute mixtures can be a challenge because a high signal-to
      noise ratio is required for the best DOSY results. The sensitivity increase
      gained from new probe technologies (e.g. cold and nano probes) could enable one
      to acquire good DOSY spectra on sample amounts too low for conventional probes.
      In this article, we investigated the performance of cold and nano probes for
      qualitative DOSY analysis of concentrated and sample-limited mixtures, and
      compared the results with those of the conventional probe. We first measured the
      fluid flow for each probe. All three probes exhibited only relatively small
      levels of flow; consequently, a double-stimulated echo pulse sequence was not
      employed in the subsequent DOSY experiments. This decision was based on three
      facts: (1) flow-induced phase distortions were not observed, (2) our intentions
      are only to perform qualitative mixture analysis, and (3) discarding 50% of the
      already limited signal cannot be afforded. Although the cold and nano probes
      produced DOSY results for the concentrated mixture that were inferior to the
      conventional probe, the increase in the signal-to-noise ratio observed with these
      probes proved to be advantageous for the dilute three-component mixture.
      Furthermore, the cold probe showed slightly superior performance over the nano
      probe; thus, we conclude that among the probes examined the cold probe is best
      suited for qualitative DOSY analysis of sample-limited mixtures.

PMID- 15505822
TI  - Anti-neuronal antibodies in patients with cancer.

PMID- 15505823
TI  - NSAIDs increase survival in the Sandhoff disease mouse: synergy with N
      butyldeoxynojirimycin.
AB  - The GM2 gangliosidoses are caused by incomplete catabolism of GM2 ganglioside in
      the lysosome, leading to progressive storage and a neurodegenerative clinical
      course. An inflammatory response (microglial activation, macrophage infiltration,
      oxidative damage) has been found to be a consequence of GM2 storage in the brain,
      although it remains unclear whether this contributes to pathogenesis or disease
      progression. In this study, we treated Sandhoff disease mice with nonsteroidal
      antiinflammatory drugs (indomethacin, aspirin, and ibuprofen) and antioxidants (L
      ascorbic acid and alpha-tocopherol acetate). The treated mice lived significantly
      longer than untreated littermates (12-23%, p <0.0001) and showed a slower rate of
      disease progression (p <0.001). When aspirin treatment was combined with
      substrate reduction therapy, synergy resulted (11%, p <0.05) with a maximum
      improvement of 73% in survival (p <0.00001). This study demonstrates that
      inflammation contributes to disease progression and identifies antiinflammatory
      and antioxidant therapies as a potential adjunctive approach to slow the clinical
      course of this and related disorders.

PMID- 15505824
TI  - Defective mitochondrial translation caused by a ribosomal protein (MRPS16)
      mutation.
AB  - The mitochondrial respiratory chain comprises 85 subunits, 13 of which are
      mitochondrial encoded. The synthesis of these 13 proteins requires many nuclear
      encoded proteins that participate in mitochondrial DNA replication, transcript
      production, and a distinctive mitochondrial translation apparatus. We report a
      patient with agenesis of corpus callosum, dysmorphism, and fatal neonatal lactic
      acidosis with markedly decreased complex I and IV activity in muscle and liver
      and a generalized mitochondrial translation defect identified in pulse-label
      experiments. The defect was associated with marked reduction of the 12S rRNA
      transcript level likely attributed to a nonsense mutation in the MRPS16 gene. A
      new group of mitochondrial respiratory chain disorders is proposed, resulting
      from mutations in nuclear encoded components of the mitochondrial translation
      apparatus.

PMID- 15505825
TI  - Deficit of in vivo mitochondrial ATP production in OPA1-related dominant optic
      atrophy.
AB  - Dominant optic atrophy has been associated with mutations in the OPA1 gene, which
      encodes for a dynamin-related GTPase, a mitochondrial protein implicated in the
      formation and maintenance of mitochondrial network and morphology. We used
      phosphorus magnetic resonance spectroscopy to assess calf muscle oxidative
      metabolism in six patients from two unrelated families carrying the c.2708
      2711delTTAG deletion in exon 27 of the OPA1 gene. The rate of postexercise
      phosphocreatine resynthesis, a measure of mitochondrial adenosine triphosphate
      production rate, was significantly delayed in the patients. Our in vivo results
      show for the first time to our knowledge a deficit of oxidative phosphorylation
      in OPA1-related DOA.

PMID- 15505826
TI  - Serum lipids and hippocampal volume: the link to Alzheimer's disease?
AB  - The association between hippocampal volume (as a presumed index of Alzheimer's
      disease pathology) with serum total cholesterol, high-density lipoprotein
      cholesterol, and low-density lipoprotein cholesterol was studied in 86 elderly
      subjects with a range of cognitive functions. High-density lipoprotein
      cholesterol, but not low-density lipoprotein cholesterol or total cholesterol,
      was associated with hippocampal volume and dementia. This is compatible with
      protective effects of high-density lipoprotein cholesterol on hippocampal atrophy
      and Alzheimer's disease.

PMID- 15505827
TI  - cAMP response element binding protein family transcription factors: the Holy
      Grail of neurological therapeutics?

PMID- 15505828
TI  - Comparison of plasma-sprayed hydroxyapatite coatings and zirconia-reinforced
      hydroxyapatite composite coatings: in vivo study.
AB  - The clinical use of plasma-sprayed hydroxyapatite (HA) coatings on metal implants
      has been widely adopted because the HA coating can achieve the firmly and
      directly biological fixation with the surrounding bone tissue. However, the long
      term mechanical properties of HA coatings has been concern for the long-term
      clinical application. Previous research showed that the concept of adding ZrO2 as
      second phase to HA significantly increased the bonding strength of plasma-sprayed
      composite material. The present work aimed to explore the biological properties,
      including the histological responses and shear strength, between the plasma
      sprayed HA and HA/ZrO2 coating, using the transcortical implant model in the
      femora of canines. After 6 and 12 weeks of implantation, the HA coating revealed
      the direct bone-to-coating contact by the backscattered electron images (BEIs) of
      scanning electron microscope (SEM), but the osseointegration was not observed at
      the surface of HA/ZrO2 coating. For new bone healing index (NBHI) and apposition
      index (AI), the values for HA implants were significantly higher than that for
      HA/ZrO2 coatings throughout all implant periods. After push-out test, the shear
      strength of HA-coated implants were statistically higher than HA/ZrO2 coated
      implants at 6- and 12-week implantation, and the failure mode of HA/ZrO2 coating
      was observed at the coating-bone interface by SEM. The results indicate that the
      firm fixation between bone and HA/ZrO2 has not been achieved even after 12-week
      implantation. Consequently, the addition of ZrO2 could improve the mechanical
      properties of coatings, while the biocompatibility was influenced by the
      different material characteristics of HA/ZrO2 coating compared to HA coatings.

PMID- 15505829
TI  - Differential effect of a bone morphogenetic protein-7 (OP-1) on primary and
      revision loaded, stable implants with allograft.
AB  - Morselized impacted bone allograft is often used to reconstruct the bone bed in
      the revision of failed total joint arthroplasties. We hypothesized that addition
      of the bone morphogenetic protein OP-1 (BMP-7) to bone allograft would improve
      early implant fixation. We inserted one loaded 6-mm-diameter titanium implant
      (surrounded by 0.75-mm gap) in each medial condyle of 24 canines. On one side,
      the implant was inserted in a controlled experimental revision setting resembling
      the clinical revision situation. A primary implant was inserted on the
      contralateral side in a previously unoperated site. Three groups were studied: 1)
      allograft alone, 2) allograft + 0.4 mg OP-1, and 3) allograft + 0.8 mg OP-1.
      Implant fixation was evaluated at 4 weeks. Grafted implants inserted in the
      primary setting without OP-1 had better fixation than the grafted revision
      setting with or without OP-1 (significantly more bone coverage, more mineralized
      tissue in the gap, and better mechanical interface strength). However, grafted
      primary implants with OP-1 had impaired fixation compared with grafted primary
      implants without OP-1 (less bone coverage of the implant and less bone formation
      in the gap). In contrast, grafted revision implants with OP-1 significantly
      increased implant fixation compared with grafted revision implants without OP-1
      (increased mechanical interface strength and fraction of mineralized tissue in
      the gap). We found no differences between the two doses in any of the settings.
      Addition of OP-1 to bone allografted implants may show benefit at sites with
      impaired bone healing capacities, such as the revision setting.

PMID- 15505833
TI  - The way to a man's heart (or head) is through his shoulder.

PMID- 15505831
TI  - Novel heparin/alginate gel combined with basic fibroblast growth factor promotes
      nerve regeneration in rat sciatic nerve.
AB  - We have developed an alginate gel crosslinked with covalent bonds for
      regeneration of dermis, nerve, and bone. Recently, a novel matrix (H/A gel) which
      consists of heparin and alginate covalently crosslinked with ethylenediamine, was
      designed. It can stabilize and release biologically active basic fibroblast
      growth factor (bFGF) for 1 month, which is one of the heparin-binding growth
      factors. In the present report, we examined the effect of this novel H/A gel on
      nerve regeneration in the rat sciatic nerve. In this study, regenerated axons in
      H/A gel with bFGF grew faster than in ordinary alginate gel with bFGF in the
      early stage. Myelinated fibers showed a tendency to increase in diameter toward
      the normal size in the later stage. Nerve bundles in the implantation exhibited
      minimal fibrosis and good vascularization. H/A gel with bFGF exhibited better
      developed vascularization than ordinary alginate gel with bFGF. These findings
      suggested that H/A gel with bFGF could serve not only as an efficient cellular
      scaffold, but also as a stabilizing matrix for bFGF for peripheral nerve
      regeneration.

PMID- 15505834
TI  - Bifurcational lesions and the "crush" technique: understanding why it works and
      why it doesn't-a kiss is not just a kiss.

PMID- 15505835
TI  - Safety and utility of intravascular ultrasound-guided carotid artery stenting.
AB  - Intravascular ultrasound (IVUS) is useful in evaluating coronary stent
      deployment. The aim of this study was to assess the safety and utility of IVUS in
      carotid artery stenting (CAS). Ninety-eight consecutive high-risk patients (107
      arteries) underwent CAS. IVUS was performed prior to predilatation in 87 of the
      107 vessels and in all 107 following stent deployment when an optimal
      angiographic appearance was obtained. Quantitative carotid angiography (QCA) and
      IVUS analysis were performed offline. Procedural success was 97%. Combined stroke
      or death at 30 days was 5.6%. IVUS measurements of the minimum lumen diameter
      (MLD) of the distal internal carotid artery (ICA) reference segment were similar
      to QCA (4.60 +/- 0.74 vs. 4.74 +/- 0.71 mm; P = 0.21). The ICA stent MLD was
      significantly smaller by IVUS compared to QCA (3.65 +/- 0.68 vs. 4.31 +/- 0.76
      mm; P < 0.001). IVUS detected stent malapposition in 11%. IVUS findings, after an
      optimal angiographic result, necessitated additional treatment in 9% of
      procedures. Calcium was detected in more arteries with IVUS than angiography (61%
      vs. 46%; P < 0.05). Arteries with superficial lesion calcification subtending
      three or four quadrants by IVUS had a 31% incidence of stroke compared with a 1%
      incidence in arteries without severe superficial calcium (P < 0.001). We found
      IVUS imaging in CAS to be safe even prior to plaque dilatation. IVUS provides a
      more accurate assessment of stent dimensions, expansion, and apposition than
      angiography. Severe calcification by IVUS was associated with a higher risk of
      stroke.

PMID- 15505836
TI  - Embolic protection pas de deux.

PMID- 15505837
TI  - Flat-panel detectors in the cardiac catheterization laboratory: revolution or
      evolution-what are the issues?
AB  - Continuous developments in digital imaging technology have contributed to the
      vital role held today by digital X-ray imaging in the cardiac catheterization
      laboratory. Foremost among these developments is the replacement of cine film
      with digital data equivalents as the procedure record. Other improvements include
      software innovations and processing algorithms, along with new types of hardware
      capable of delivering required functionality more rapidly. A significant recent
      development is that of the flat-panel X-ray detector as a replacement for the
      image intensifier, which has served the needs of the cardiac catheterization
      laboratory for nearly 5 decades. Clinical users must evaluate the respective
      technologies and determine whether one or the other meets the needs of their own
      laboratories. In this review, the two competing detector technologies are
      reviewed and a summary of general advantages and disadvantages of each is
      provided. A qualitative description is provided of parameters that can be used to
      assess quantitatively the performance of detectors and imaging systems. Using
      such objective measurements, together with standard techniques for evaluating
      imaging systems, angiographers and managers can better arrive at informed
      decisions for their own situation.

PMID- 15505838
TI  - Vascular access site complications with the use of closure devices in patients
      treated with platelet glycoprotein IIb/IIIa inhibitors during rescue angioplasty.
AB  - The objective of this study was to evaluate the effectiveness of two different
      closure devices in patients undergoing rescue percutaneous coronary intervention
      (PCI) using IIb/IIIa inhibitors and to compare it with patients undergoing
      elective PCI. One hundred sixty-two patients undergoing rescue PCI treated with
      IIb/IIIa inhibitors underwent vascular access site closure (6 Fr Perclose, n =
      92, or 6 Fr Angioseal, n = 70). Vascular complications were compared with a sex-
      and age-matched group (n = 100) of patients undergoing manual compression after
      sheath removal and a similar group of patients undergoing elective PCI (n = 196).
      The incidence of access site complications was not significantly different
      between the three groups undergoing rescue PCI and was not higher than in patient
      receiving GP IIb/IIIa inhibitors without fibrinolysis (RR = 0.95; 95% CI = 0.88
      1.01). In patients undergoing rescue PCI and receiving IIb/IIIa inhibitors,
      closure devices allow early sheath removal and are associated with similar
      outcomes compared with manual compression and elective PCI regardless of the type
      of closure device used.

PMID- 15505839
TI  - Improved performance of a new thrombus aspiration catheter: outcomes from in
      vitro experiments and a case presentation.
AB  - Thrombus vacuum catheter (TVAC) is a new thrombus aspiration catheter. The
      catheter has a beak-shaped distal tip and a shaft with spring support. Based on
      in vitro tests, these design features showed improved ability to pass through a
      simulated coronary artery model with a bend and to aspirate gel. TVAC has an
      outer diameter of 4.5 Fr and is available with a 7 Fr guide. We report a case of
      acute myocardial infarction that was successfully treated with TVAC after use of
      other aspiration devices failed in its treatment. Since protection of
      microcirculation in coronary reperfusion may be essential in acute myocardial
      infarction, TVAC is a promising device to help achieve this goal.

PMID- 15505841
TI  - Sirolimus-eluting stents for the prevention of restenosis in a worst-case
      scenario of diffuse and recurrent in-stent restenosis.
AB  - For recurrent in-stent restenosis (ISR), surgical revascularization or
      brachytherapy is still the principal therapeutic options. The present
      investigation explores the efficacy of a sirolimus-eluting stent to prevent
      restenosis in these lesions with a high risk of recurrence. In 22 consecutive
      patients with a recurrent and diffuse ISR, a sirolimus-eluting stent was
      implanted to cover the restenotic lesion. All patients were followed clinically
      for at least 1 year and underwent a repeat angiography after 7 months. A
      quantitative coronary angiographic analysis was done. The target vessel failure
      was 14% in the sirolimus-eluting stent group, with an angiographic late loss of
      only 0.39 +/- 0.54. No subacute stent thrombosis was observed, and the 1-year
      event-free survival was 86%. The three cases with restenosis were all focal and
      could be successfully treated by additional drug-eluting stent implantation. This
      study showed the efficacy of a sirolimus-eluting stent for the prevention of
      restenosis in a worst-case scenario of recurrent and diffuse ISR. The observed
      restenosis rate is lower than that reported after brachytherapy and suggests that
      sirolimus-eluting stents are a promising treatment option for ISR.

PMID- 15505842
TI  - High-output congestive heart failure successfully treated with transcatheter coil
      embolization of a large renal arteriovenous fistula.
AB  - Left heart catheterization was performed in response to progressive congestive
      heart failure of uncertain etiology in a 59-year-old male. The coronary arteries
      were normal but screening abdominal aortography revealed a large arterial venous
      communication between the left inferior segmental renal artery and the
      ipsilateral renal vein. The massive size and brisk flow patterns in the fistula
      presented technical challenges for transcatheter closure. The use of multiple
      Amplatz vascular obstructive devices (spiders) to create a matrix for securing
      subsequent coils in staged procedures and the patient's progress following
      successful closure are discussed.

PMID- 15505843
TI  - Carotid artery surgery vs. stent: a cardiovascular perspective.
AB  - Stroke is a major health catastrophe that is responsible for the third most
      common cause of death and the leading cause of disability. Carotid artery
      stenosis is an important cause of brain infarctions and the risk of stroke is
      directly related to the severity of carotid artery stenosis and to the presence
      of symptoms. Familiarity with different methods of measuring degrees of carotid
      artery stenosis is a key in understanding the role of revascularization of this
      disorder. Carotid endarterectomy (CEA), surgical removal of the carotid
      atherosclerotic plaque, is intended to prevent stroke in patients with carotid
      artery stenosis and currently the most commonly performed vascular procedure in
      the United States. Several randomized clinical trials had demonstrated the
      benefits of CEA in selected groups of patients with symptomatic and asymptomatic
      carotid artery stenosis. However, CEA can cause stroke, the very thing it
      intended to prevent, and is associated with significant perioperative
      complications such as those related to general anesthesia, cardiac or nerve
      injury. Moreover, several anatomical and medical conditions may limit candidates
      for CEA. Carotid artery stenting (CS) is an evolving and less invasive technique
      for carotid artery revascularization. Recent studies demonstrated that CS with
      embolic protection devices has become an alternative to CEA for high-surgical
      risk patients and the procedure of choice for stenoses inaccessible by surgery.
      The role of CS in low risk patients awaits the completion of several ongoing
      studies.

PMID- 15505844
TI  - Sometimes less is just less.

PMID- 15505845
TI  - Infective endocarditis after transcatheter closure of a patent foramen ovale.
AB  - Infection of devices for percutaneous transcatheter closure of atrial septal
      defects are exceedingly rare. Two cases of device-associated endocarditis have
      been reported, which were both operated on. We describe the successful treatment
      with antibiotics of a device-associated endocarditis.

PMID- 15505846
TI  - Combined catheter ventricular septal defect closure and multivessel coronary
      stenting to treat postmyocardial infarction ventricular septal defect and triple
      vessel coronary artery disease: a case report.
AB  - Ventricular septal defect following acute myocardial infarction is a rare but
      life-threatening complication. Early surgical closure improves survival but
      carries a considerable risk. Percutaneous transcatheter closure is an alternative
      but experience to date is limited. We report a case of successful transcatheter
      closure of postmyocardial infarction ventricular septal defect (VSD) in a 55-year
      old male with the Amplatzer muscular VSD occluder device and complete
      percutaneous revascularization with successful multivessel coronary stenting for
      three-vessel disease as a staged procedure. The technique and its potential use
      as an alternative to surgical approach for treatment of acute myocardial
      infarction and its complication (VSD) are discussed.

PMID- 15505847
TI  - Use of gadobutrol in coronary angiography.
AB  - Gadobutrol was used in coronary angiography in three patients. All three patients
      had a substantially increased risk of developing renal complications with
      iodinated contrast agents. Gadobutrol was well tolerated in all three patients
      without any complications. The quality of the coronary angiograms was good.

PMID- 15505849
TI  - The cough that resuscitated Dr. F. Mason Sones's first patient undergoing
      selective cine coronary arteriography.

PMID- 15505848
TI  - Initial clinical experience with intracardiac echocardiography in guiding balloon
      mitral valvuloplasty: technique, safety, utility, and limitations.
AB  - The objective of this study was to examine the feasibility and technique of
      intracardiac echocardiography during percutaneous balloon mitral valvuloplasty.
      Echocardiographic imaging is commonly used during mitral valvuloplasty.
      Intracardiac echocardiography is a newer technology that may provide superior
      imaging during complex valvular interventions. Intracardiac echocardiography and
      transthoracic echocardiography were performed in 19 patients undergoing
      percutaneous balloon mitral valvuloplasty. Intracardiac ultrasound images were
      obtained via the femoral vein in all patients. Imaging projections and catheter
      locations that were useful for the performance of mitral valvuloplasty were
      defined. Intracardiac echocardiography guided transseptal puncture, augmented the
      assessment of valve apparatus deformity, facilitated balloon positioning across
      the mitral valve, and permitted postprocedural valvular assessment including
      identification of mitral regurgitation with color Doppler. Intracardiac
      echocardiography provided essential imaging guidance and procedural monitoring
      during percutaneous mitral valvuloplasty.

PMID- 15505850
TI  - Gadolinium-based balloon angioplasty for pulmonary artery stenosis in an infant
      with a right isomerism.
AB  - We report here the first described case of utilizing gadolinium-based contrast
      material as the contrast agent during a catheter intervention treatment for
      pulmonary artery stenosis. The patient, a male infant with complex heart disease
      associated with a right isomerism, had a history of severe allergic reaction to
      iodine-containing contrast agents. A combination of digital subtraction
      angiography and a gadolinium contrast agent, however, provided us with good
      quality images both before and after balloon angioplasty without any associated
      complications. This method should therefore be considered as an alternative
      angiographic procedure in children with a high risk of iodine-related allergic
      complications.

PMID- 15505851
TI  - Endovascular treatment of the subclavian artery: stent implantation with or
      without predilatation.
AB  - The endovascular treatment of subclavian artery (SA) lesions is less invasive
      than open surgical repair, with a low rate of complications. We report our
      experience in 89 subclavian obstructive lesions (n = 86) treated with stenting:
      76 (85.3%) stenoses and 13 (14.6%) total occlusions. The left side was most
      frequently involved (83.1%), localized at the prevertebral segment in 91%.
      Technical success was obtained in 83 (93.3%) cases, 100% in stenotic lesions and
      53.8% in total occlusions. There were nine global complications (10.1%): five
      (5.6%) at site of puncture, two distal embolization (2.2%), and two (2.3%) major
      events. The long-term follow-up was 3.51 +/- 1.98 years, during which time 13
      (16.8%) restenoses and 2 (2.6%) reocclusions were noted. Subgroup analysis of
      patients with stenting after predilatation versus direct stenting technique
      showed in-hospital complications only in the first group, with a restenosis rate
      of 28.5% vs. 4.7%, respectively (P = 0.003). We consider stenting for SA
      obstructive lesions the first therapeutic option.

PMID- 15505852
TI  - Ruptured plaque.

PMID- 15505853
TI  - Drug-eluting stents for coronary bifurcations: insights into the crush technique.
AB  - Sirolimus-eluting stents appear to reduce substantially restenosis following
      percutaneous coronary bifurcation intervention. The crush technique was devised
      to reduce restenosis further by improving stent and drug application to the side
      branch ostium. We aimed to investigate the performance of drug-eluting stent
      (DES) platforms with the crush technique, to identify deployment pitfalls, and to
      clarify the best deployment strategies. Each stage of the crush technique was
      photographed in a bifurcation phantom. Simultaneous side- and main-branch
      dilatation (kissing balloons) fully expanded the stent in the side-branch ostium,
      widened the gaps between stent struts covering the side branch, and eliminated
      main-branch distortion. With side branches angled at > 70 degrees , sequential
      (side- then main-branch) inflations may be needed to achieve best results.
      Postdilatation of the main branch with a balloon of narrower diameter than the
      deploying balloon caused main-branch stent distortion. These principles applied
      to all the bifurcation strategies and stent designs tested.

PMID- 15505854
TI  - Percutaneous intervention of a bifurcating saphenous vein graft with simultaneous
      dual-limb filter wire protection.
AB  - Distal embolization during saphenous vein graft angioplasty may result in
      myocardial infarction. The use of dual nonocclusive filter wire during
      angioplasty in a bifurcating saphenous vein graft is described.

PMID- 15505855
TI  - Intravascular ultrasound evaluation of ruptured plaque in the left main coronary
      artery misinterpreted as an aneurysm by angiography.
AB  - We report a patient who demonstrated a left main coronary aneurysm by
      angiography. Intravascular ultrasound (IVUS) revealed that it was in fact an
      ulceration, which indicated ruptured plaque. This case provides evidence that
      IVUS can permit a more powerful definition of ruptured plaque than angiography.
      On IVUS, ulceration exhibits significantly different characteristics from
      aneurysm.

PMID- 15505856
TI  - Ionizing radiation and the coronary arteries: is the plot thickening?

PMID- 15505857
TI  - Hemodynamic abnormalities across an anomalous left main coronary artery
      assessment: evidence for a dynamic ostial obstruction.
AB  - Anomalous left main coronary arteries have been associated with sudden cardiac
      death, especially when arising from the right coronary cusp and following an
      anterior course. To date, imaging procedures have been the mainstay of the
      decision-making process in determining which patients should undergo surgery for
      correction of this anomaly and which patients are presumed to be at low risk. We
      report on the hemodynamic evaluation of an anomalous left main performed in
      support of elected surgical correction in a young patient.

PMID- 15505858
TI  - Drug-eluting stents for secondary prevention of restenosis.

PMID- 15505859
TI  - Noncardiac surgery following percutaneous coronary intervention.
AB  - Patient with coronary artery disease (CAD) undergoing major noncardiac surgery
      (NCS) are at increased risk of serious perioperative cardiac complications. At
      the same time, safety of percutaneous coronary intervention (PCI) before
      noncardiac surgery has been questioned. This paper reviews the available
      literature regarding the safety of PCI before NCS. At the same time, cardiac
      evaluation before NCS, perioperative medical management of patients undergoing
      NCS, and percutaneous coronary intervention and timing of NCS is also discussed.

PMID- 15505860
TI  - Intraprocedure guidance for percutaneous mitral valve interventions: TTE, TEE,
      ICE, or X-ray?

PMID- 15505861
TI  - Clopidogrel resistance.

PMID- 15505862
TI  - Atypical hemodynamic manifestations of cardiac tamponade.
AB  - Clinical examination and transthoracic echocardiography play a vital role in the
      management of patients with pericardial effusion and cardiac tamponade
      physiology. We report patients in advanced phase 3 cardiac tamponade with variant
      clinical and hemodynamic presentations. These atypical cardiac tamponade cases
      include: A patient with severe aortic valve regurgitation who lacked pulsus
      paradoxus; a patient with systemic sclerosis without hypotension; and a patient
      with pulmonary hypertension lacking right heart collapse on echocardiography.
      Recognition of these atypical clinical and hemodynamic manifestations of cardiac
      tamponade will avoid undue delay in the treatment.

PMID- 15505863
TI  - A view from within.

PMID- 15505864
TI  - Pseudoperforation during kissing balloon angioplasty.
AB  - We describe a case of apparent perforation during kissing balloon angioplasty of
      a bifurcation lesion. There was no evidence of perforation on follow-up
      angiography or via intravascular ultrasound. Possible etiologies include minimal
      perforation that immediately sealed postdeflation or forced contrast into the
      microvascular bed via a proximal side branch.

PMID- 15505865
TI  - Prognostic value of the flat fluoroscopic detector.

PMID- 15505866
TI  - An 11-year experience of enterocutaneous fistula.
AB  - BACKGROUND: Enterocutaneous fistula has traditionally been associated with
      substantial morbidity and mortality, related to fluid, electrolyte and metabolic
      disturbance, sepsis and malnutrition. METHODS: A retrospective review of
      enterocutaneous fistula in 277 consecutive patients treated over an 11-year
      period in a major tertiary referral centre was undertaken to evaluate current
      management practice and outcome. RESULTS: Most fistulas occurred secondary to
      abdominal surgery, and a high proportion (52.7 per cent) occurred in association
      with inflammatory bowel disease. A low rate of spontaneous healing was observed
      (19.9 per cent). The healing rate after definitive fistula surgery was 82.0 per
      cent, although more than one attempt was required to achieve surgical closure in
      some patients. Definitive fistula resection resulted in a mortality rate of 3.0
      per cent. In addition, one patient died after laparotomy for intra-abdominal
      sepsis and an additional 24 patients died from complications of fistulation,
      giving an overall fistula-related mortality rate of 10.8 per cent. CONCLUSION:
      Early recognition and control of sepsis, management of fluid and electrolyte
      imbalances, meticulous wound care and nutritional support appear to reduce the
      mortality rate, and allow spontaneous fistula closure in some patients.
      Definitive surgical management is performed only after restitution of normal
      physiology, usually after at least 6 months.

PMID- 15505867
TI  - Two-year clinical follow-up results of intracoronary radiation therapy with
      rhenium-188-diethylene triamine penta-acetic acid-filled balloon.
AB  - We investigated the 2-year clinical follow-up results as well as 6-month
      angiographic and clinical follow-up results of intracoronary radiation therapy
      using a rhenium-188-diethylene triamine penta-acetic acid ((188)Re-DTPA)-filled
      balloon system. The study comprised of 161 patients with significant de novo
      (83%) or in-stent restenosis (17%) lesions. Irradiation to deliver 17.6 Gy at a
      depth of 1.0 mm into the vessel wall was carried out after successful
      intervention. At 6-month follow-up, binary restenosis developed with
      significantly lower frequency in the radiation group than in the control group
      (24.3% vs. 46.3%; P = 0.009), although target lesion revascularization rate did
      not show significant benefit. At 2-year follow-up, cumulative target lesion
      revascularization rate was not significantly different between radiation group (n
      = 86) and control group (n = 75; 20.0% vs. 26.0%; P = 0.368). The rate of major
      adverse cardiac events including death, myocardial infarction, and target lesion
      revascularization did not show significant difference between two groups either
      (22.3% vs. 30.1%; P = 0.266). In conclusion, although significant reduction in
      restenosis rate was noted at 6-month angiographic follow-up, intracoronary
      radiation therapy mostly in patients with de novo lesion did not show significant
      clinical benefit in 6-month and 2-year follow-up results. The benefit was noted
      only in a small subgroup of patients with in-stent restenosis.

PMID- 15505868
TI  - Pathological determinants of survival in node-negative oesophageal cancer.
AB  - BACKGROUND: Many studies have analysed prognostic factors following
      oesophagectomy, but few have examined survival determinants in node-negative (N0)
      oesophageal cancer. The prognostic significance of a number of histological
      variables following surgical resection of N0 oesophageal cancer was studied.
      METHODS: The case notes of 219 patients undergoing potentially curative
      oesophagectomy for N0 squamous cell carcinoma or adenocarcinoma of the oesophagus
      were reviewed. Details of the patient's sex, age at operation, histological type,
      longitudinal tumour length, tumour (T) stage, circumferential resection margin
      involvement, tumour grade, presence of vascular invasion, perineural invasion,
      Barrett's metaplasia, and survival were noted. Univariate and multivariate
      analyses were performed to identify prognostic factors. RESULTS: Univariate
      analysis revealed three factors that correlated with poor prognosis: T stage (P =
      0.024), adenocarcinoma (P = 0.033) and degree of differentiation (P = 0.001).
      Multivariate analysis revealed that all three were significant independent
      adverse prognostic indicators. CONCLUSION: Surgical resection of node-negative
      oesophageal cancer is associated with diverse long-term outcomes. This diversity
      of outcome is not reflected in the tumour node metastasis (TNM)-based staging
      system. The utility of the TNM system in predicting prognosis after surgical
      resection is open to question.

PMID- 15505869
TI  - Autopsy findings from 111 deaths in the 1999 Athens earthquake as a basis for
      auditing the emergency response.
AB  - BACKGROUND: The aim of the study was to assess the emergency response to an
      earthquake. METHODS: This retrospective study, based on formal autopsy findings
      from 111 earthquake-related deaths, evaluated demographic data, circumstances of
      death, rescue time, mechanisms of injury, causes of death, Abbreviated Injury
      Scale (AIS 90) and Injury Severity Score (ISS) values, vital functions, co
      morbidity and preventable deaths. RESULTS: The median extrication time for 99 of
      102 victims buried or trapped in collapsed buildings was 2.1 (range 0.1-7.8)
      days. Deaths were cause by blunt injuries, asphyxia and myocardial infarction.
      Injuries impaired the airway, breathing, circulation, and brain or spinal
      functions in 10.5, 61.9, 46.6 and 57.1 per cent of the victims respectively. The
      105 injured victims were classified into three main categories. The first
      comprised 36 victims (34.3 per cent) with injuries not compatible with life (ISS
      75), the second included 38 victims (36.2 per cent) who suffered life-threatening
      injuries (ISS 9-74) but had no evidence of asphyxia, and the third category
      contained 31 victims (29.5 per cent) with findings of asphyxia and an ISS of 1
      18. The reviewers concluded that 13 trauma-related deaths and 31 deaths from
      asphyxia were potentially preventable. CONCLUSION: A method based on detailed
      evaluation of deaths provided information with which to audit the emergency
      response to an earthquake.

PMID- 15505870
TI  - Surgical management of primary and recurrent retroperitoneal liposarcoma.
AB  - BACKGROUND: Surgery plays a dominant role in the initial and subsequent treatment
      of retroperitoneal liposarcoma (RPLS). This study was a review of outcomes of
      patients treated at the Royal Marsden Hospital. METHODS: Records of all patients
      who had surgery for RPLS since 1990 were reviewed, with particular attention to
      local recurrence and disease-specific survival. Patients with primary RPLS and
      those with recurrent RPLS, who had palliative surgery after a variable number of
      operations performed elsewhere, were considered separately. RESULTS: Seventy-two
      patients had surgery for primary RPLS, over half of whom underwent resection of a
      contiguous organ to achieve clearance. Follow-up of at least 12 months was
      available for 58 patients. Thirty-four patients had no evidence of recurrence
      after median follow-up of 26 (range 12-151) months. Low-grade tumour and
      macroscopic clearance of tumour were significantly associated with a reduced risk
      of local recurrence and improved survival. Forty-seven patients had palliative
      surgery for recurrent RPLS. Median survival from time of last operation to death
      was 27 (range 0-79) months. Follow-up was to a median of 68 (range 14-261)
      months. CONCLUSION: Patients with low-grade RPLS that has been completely
      resected at the initial operation have the most favourable prognosis. Palliative
      resection is worthwhile to treat troublesome symptoms of recurrence.

PMID- 15505871
TI  - Effects of a selective cyclo-oxygenase 2 inhibitor on colonic anastomotic and
      skin wound integrity.
AB  - BACKGROUND: Selective inhibitors of inducible cyclo-oxygenase (COX-2) are of
      potential benefit in the perioperative period for both their analgesic and,
      perhaps, antineoplastic actions. However, their effects on laparotomy and
      intestinal wound healing are unknown. METHODS: Forty adult Sprague-Dawley rats
      underwent laparotomy, descending colonic transection and handsewn reanastomosis.
      The animals were randomized to receive either a selective COX-2 inhibitor
      (rofecoxib, 10 mg/kg) or an equal volume of water by gavage before operation and
      then daily after surgery. Animals were killed after 3 or 7 days, and their wounds
      were evaluated by means of tensiometry (skin and colonic wounds) and bursting
      pressure measurement (colonic anastomoses). In addition, haematoxylin and eosin
      stained intestinal sections were examined and scored by a blinded independent
      observer. RESULTS: Five animals that received rofecoxib had anastomotic leaks by
      day 7 compared with none in the control group (P = 0.048). Intact colonic suture
      lines were also significantly weaker in this group (tensile strength at day 3, P
      = 0.043; bursting pressure on days 3 and 7, both P = 0.019). Skin wound strengths
      were similar in the two groups at both time points. CONCLUSION: Although
      beneficial in the treatment of pathological inflammation, selective COX-2
      inhibitors may adversely affect colonic anastomotic healing.

PMID- 15505872
TI  - Transdiaphragmatic pleural lavage in penetrating thoracoabdominal trauma.
AB  - BACKGROUND: The purpose of this study was to determine the incidence of thoracic
      sepsis following a systematic thoracic cavity washout through the injured
      diaphragm in patients with penetrating thoracoabdominal trauma. METHODS:
      Prospectively collected data on all patients presenting with penetrating
      thoracoabdominal trauma between July 1999 and July 2002 were analysed. Patients
      with peritoneal biliary-gastroenteric (BGE) contamination and a diaphragmatic
      laceration were managed by laparotomy and transdiaphragmatic thoracic lavage.
      RESULTS: A total of 217 patients had penetrating thoracoabdominal injuries, of
      whom 110 had BGE contamination of the peritoneal cavity with spillage into the
      pleural cavity. The mean Injury Severity Score was 38.1. Gunshot and stab wounds
      occurred in 79 (71.8 per cent) and 31 (28.2 per cent) respectively. Contamination
      was from the stomach (55.4 per cent), large bowel (37.3 per cent), small bowel
      (29.1 per cent), gallbladder and bile ducts (9.1 per cent) and pancreas (6.4 per
      cent). Thoracic complications occurred in six patients (5.5 per cent): empyema in
      two, Escherichia coli-related pneumonia in three and pleuritis in one. There were
      no deaths. CONCLUSION: A thoracic washout through the injured diaphragm in
      patients with penetrating thoracoabdominal trauma and BGE contamination was
      associated with a low rate of intrathoracic septic complications.

PMID- 15505873
TI  - Implications of screening for abdominal aortic aneurysms on surgical workload.
AB  - BACKGROUND: The Multicentre Aneurysm Screening Study (MASS) provided strong
      evidence for both the clinical benefit and the cost-effectiveness of a screening
      programme for abdominal aortic aneurysms (AAAs) in men. If a national screening
      programme for AAA were adopted in the UK, it would be expected to increase the
      elective and decrease the emergency surgical workload. METHODS: The MASS trial
      randomized 67,800 men aged 65-74 years to be invited to attend for
      ultrasonographic screening for AAA or to a control group that received no
      invitation. Predictions of elective and emergency surgical workload were made for
      a 20-year interval after the introduction of a screening programme for 65-year
      old men, based on surgical rates observed in the MASS trial and national
      mortality statistics. RESULTS: For a district general hospital serving a
      population of 400,000, there was an estimated reduction from nine emergency
      operations per year before introduction of the screening programme to three
      emergency operations annually in men aged 65 years and over by the end of the 20
      year interval, and an increase from 24 to 43 AAA operations overall. The
      corresponding estimated annual costs for all AAA surgery increased by 47 per
      cent, from pound 209,000 to pound 308,000. These results were not affected by
      changes in the underlying assumptions. CONCLUSION: The results support the
      expectation of very few emergency operations, and principally elective
      operations, being performed following the introduction of a screening programme.
      For a typical district general hospital, a screening programme would be expected
      to lead to two additional elective AAA operations per month, and to save 11 AAA
      related deaths per year.

PMID- 15505874
TI  - Factors affecting women's preference for type of prenatal screening test for
      chromosomal anomalies.
AB  - OBJECTIVE: To ascertain, by means of a questionnaire, women's preferences for
      four different approaches to prenatal screening for Down syndrome. METHODS: Women
      attending antenatal clinics at six UK maternity units were asked to put in order
      of preference four different approaches to screening for Down syndrome all of
      which had the same false positive rate of 5%. The options were: (1) first
      trimester testing, 90% detection of Down syndrome with results available in 1 h
      at one-stop clinics for the assessment of risk (OSCAR); (2) first-trimester
      testing, 90% detection and results available within 2-3 days (combined
      screening); (3) first-trimester testing plus second-trimester testing, 93%
      detection and results available within 2-3 days of second test (integrated
      testing); (4) second-trimester testing, 75% detection and results available
      within 2-3 days. RESULTS: Over 1100 women attending antenatal clinics at six
      maternity units across the UK returned the questionnaire. A total of 75% of women
      selected a first-trimester test (option 1 or option 2) as their first choice with
      68.2% expressing a preference for the OSCAR approach and a further 6.8% for
      combined screening. Twenty-four percent of women opted for integrated testing as
      their first choice with only 1% expressing a preference for second-trimester
      screening. CONCLUSIONS: A first-trimester test is preferred by the majority of
      women over a test with marginally higher detection rate that delivers results
      later in pregnancy. Timing and rapid reporting of results appear to influence
      women's choice of test.

PMID- 15505875
TI  - Randomized clinical trial comparing radioisotope occult lesion localization and
      wire-guided excision for biopsy of occult breast lesions.
AB  - BACKGROUND: Accurate localization of impalpable breast lesions that require
      biopsy is important. This randomized trial compared radioisotope occult lesion
      localization (ROLL) with the standard hooked-wire technique. METHODS: Ninety-five
      patients were randomized to receive either ROLL or wire localization of an occult
      breast lesion. Correct placement of isotope was confirmed by mammography and a
      hand-held gamma probe was used to guide the surgical excision. Radiological,
      surgical and pathological data were compared for accuracy, duration and ease of
      technique, and histopathological diagnosis. Procedure-related pain was also
      assessed. RESULTS: Of the 95 patients entered, 48 were randomized to ROLL and 47
      to wire localization. Two ROLL procedures failed. Marking was accurate in 46 of
      48 ROLL procedures and 44 of 47 of wire localizations (P = 0.242). Difficulty in
      localization (Likert score 2.6 for ROLL versus 4.4 for wire localization; P <
      0.001) and the degree of surgical difficulty (2.6 versus 4.0; P < 0.001) were
      significantly less for ROLL. ROLL was associated with less pain (score 2.7 versus
      3.6; P = 0.012). There were no significant differences in mean duration of
      operation, specimen weight, need for intraoperative re-excision or second
      therapeutic operation. CONCLUSION: ROLL and wire-guided localization were
      similarly effective for breast biopsy, but ROLL was easier for both radiologist
      and surgeon, and less painful for the patient.

PMID- 15505876
TI  - Effects of warm-up on exercise capacity, platelet activation and platelet
      leucocyte aggregation in patients with claudication.
AB  - BACKGROUND: The effects of exercise and warm-up were investigated in patients
      with claudication. METHODS: This case-control crossover study involved two
      treadmill exercise tests, one preceded by a warm-up. Exercise continued until
      maximal leg pain (patients with claudication) or exhaustion (controls). Blood was
      taken before, and 5 and 60 min after exercise for flow cytometric analysis of
      platelet activation and platelet-leucocyte aggregation. RESULTS: Both cohorts
      (eight patients with claudication of median age 63 years and eight healthy
      controls of median age 63.5 years) demonstrated improvement in exercise capacity
      after warm-up (13.1 per cent, P = 0.012 and 15.6 per cent, P = 0.008
      respectively). Platelet activation increased after exercise in patients with
      claudication (fibrinogen binding: 1.11 per cent before exercise versus 2.63 per
      cent after exercise, P = 0.008; P-selectin: 0.68 versus 1.11 per cent, P =
      0.028). Neither agonist stimulation nor warm-up altered this trend. Platelet
      leucocyte (PLA) and platelet-neutrophil (PNA) aggregation were similarly
      increased immediately after exercise in patients with claudication (PLA: 7.6
      versus 13.0 per cent, P = 0.004; PNA: 6.8 versus 10.2 per cent, P = 0.012). These
      remained high 60 min after exercise only in patients with claudication, but
      recovered to baseline levels when preceded by warm-up. Warm-up significantly
      desensitized PNA after stimulation with 10 micromol/l adenosine 5'-diphosphate at
      all time points. CONCLUSION: Warm-up increased the exercise capacity of patients
      with claudication. Exercise induced a thromboinflammatory response, with PLA and
      PNA persistently increased after 60 min in patients with claudication, an effect
      diminished after warm-up.

PMID- 15505877
TI  - A systematic review of the ultrasound estimation of fetal weight.
AB  - OBJECTIVES: The range and use of ultrasound fetal measurements have gradually
      been extended. Measurements have been combined to estimate fetal weight by
      mathematically based non-linear regression analysis or physically based
      volumetric methods. Fetal weight estimation is inaccurate, with poor sensitivity
      for prediction of fetal compromise. Several authors have shown the unacceptable
      level of intra- and interobserver variability in fetal measurement and the impact
      of errors on growth assessment. The aims of this study were to review the
      available methods and possible sources of inaccuracy. METHODS: Four databases
      were searched for studies comparing ultrasound estimated fetal weight (EFW) with
      birth weight. Studies meeting the inclusion criteria evaluated 11 different
      methods. Errors were graphically summarized. RESULTS: No consistently superior
      method has emerged. Volumetric methods provide some theoretical advantages.
      Random errors are large and must be reduced if clinical errors are to be avoided.
      CONCLUSIONS: The accuracy of EFW is compromised by large intra- and interobserver
      variability. Efforts must be made to minimize this variability if EFW is to be
      clinically useful. This may be achieved through averaging of multiple
      measurements, improvements in image quality, uniform calibration of equipment,
      careful design and refinement of measurement methods, acknowledgment that there
      is a long learning curve, and regular audit of measurement quality. Further work
      to improve the universal validity and accuracy of fetal weight estimation
      formulae is also required.

PMID- 15505878
TI  - Aggressive fibromatosis of the abdominal wall, limbs and limb girdles.
AB  - BACKGROUND: Aggressive fibromatosis (AF) is a rare soft-tissue tumour. It is
      histologically benign but locally aggressive and destructive. Surgery is the
      mainstay of treatment. This was a review of patients treated at the Royal Marsden
      Hospital between 1986 and 2003. METHODS: Records of patients with abdominal wall
      (23) and limb or limb girdle (86) AF were studied to determine patient, tumour
      and treatment characteristics and outcome. Children and patients with intra
      abdominal AF were excluded. The data were analysed by Cox regression to calculate
      univariate hazard ratios. RESULTS: Twenty-one (19.3 per cent) of 109 patients
      developed recurrence after a median follow-up of 39 months. Recurrence did not
      correlate with surgical margin or any other variable. CONCLUSION: Wide
      excisional, function-preserving surgery is the goal in treatment of AF. Surgery
      for recurrent disease is often curative. Tumours are frequently irresectable at
      presentation and an initial period of expectant observation is advisable because
      growth arrest is a common feature of the disease.

PMID- 15505880
TI  - Coupled hydrogen-bonding networks in polyhydroxylated peptides.

PMID- 15505881
TI  - Chiral metal-organic assemblies--a new approach to immobilizing homogeneous
      asymmetric catalysts.

PMID- 15505879
TI  - Ovarian cancer in Europe: Cross-sectional trends in incidence and mortality in 28
      countries, 1953-2000.
AB  - We have considered trends in incidence and mortality in 28 European countries
      using incidence data from successive volumes of Cancer Incidence in Five
      Continents and mortality from the WHO database. Countries with the highest rates
      in the early 1960s included the Nordic countries, Austria, Germany and the United
      Kingdom, but trends in these areas have tended to decline over recent calendar
      periods, particularly with regard to mortality. Southern European countries
      showed upward trends, at least until the early 1980s for France and Italy.
      Likewise, in most central and eastern European countries, ovarian cancer
      incidence and mortality rates were originally relatively low, but tended to rise
      over time. Falls in mortality, but not in incidence, over recent years were
      observed in the Czech Republic and Hungary. In several countries, mainly in
      northern Europe, trends were more favorable at younger age (25-49 years) than in
      the subsequent age groups. Thus, recent trends in ovarian cancer have led to a
      leveling of rates across various areas of the continent, although a 2.5-fold
      variation was still observed in the late 1990s between the highest mortality rate
      of 9.3/100,000 in Denmark and the lowest one of 3.6 in Portugal. These patterns
      should be viewed in the light of an observed reduction in parity, mainly in
      southern and eastern Europe, and the spread of oral contraceptive use, mainly in
      northern Europe, since these are the best recognized protective factors with
      regard to ovarian carcinogenesis. The declining mortality trends can also in part
      be ascribed to improvements in treatment.

PMID- 15505884
TI  - Using the area under the curve to reduce measurement error in predicting young
      adult blood pressure from childhood measures.
AB  - Tracking correlations of blood pressure, particularly childhood measures, may be
      attenuated by within-person variability. Combining multiple measurements can
      reduce this error substantially. The area under the curve (AUC) computed from
      longitudinal growth curve models can be used to improve the prediction of young
      adult blood pressure from childhood measures. Quadratic random-effects models
      over unequally spaced repeated measures were used to compute the area under the
      curve separately within the age periods 5-14 and 20-34 years in the Bogalusa
      Heart Study. This method adjusts for the uneven age distribution and captures the
      underlying or average blood pressure, leading to improved estimates of
      correlation and risk prediction. Tracking correlations were computed by race and
      gender, and were approximately 0.6 for systolic, 0.5-0.6 for K4 diastolic, and
      0.4-0.6 for K5 diastolic blood pressure. The AUC can also be used to regress
      young adult blood pressure on childhood blood pressure and childhood and young
      adult body mass index (BMI). In these data, while childhood blood pressure and
      young adult BMI were generally directly predictive of young adult blood pressure,
      childhood BMI was negatively correlated with young adult blood pressure when
      childhood blood pressure was in the model. In addition, racial differences in
      young adult blood pressure were reduced, but not eliminated, after controlling
      for childhood blood pressure, childhood BMI, and young adult BMI, suggesting that
      other genetic or lifestyle factors contribute to this difference.

PMID- 15505885
TI  - A new parametric model for survival data with long-term survivors.
AB  - We develop a new parametric model using the three-parameter Burr XII distribution
      for the analysis of survival data with long-term survivors, which includes the
      previous Weibull mixture model as a special case. The new model is applied to the
      analysis of a set of leukaemia data for which previous attempts in the literature
      using traditional parametric models were unsatisfactory due to lack of fit. It is
      shown that the new model improves the fit to the leukaemia data significantly and
      is thus capable of providing more credible answers to a variety of statistical
      inference problems that are of interest to medical researchers and practitioners.

PMID- 15505886
TI  - Ordered multiple-class ROC analysis with continuous measurements.
AB  - Receiver operating characteristic (ROC) curves have been useful in two-group
      classification problems. In three- and multiple-class diagnostic problems, an ROC
      surface or hyper-surface can be constructed. The volume under these surfaces can
      be used for inference using bootstrap techniques or U-statistics theory. In this
      article, ROC surfaces and hyper-surfaces are defined and their behaviour and
      utility in multi-group classification problems is investigated. The formulation
      of the problem is equivalent to what has previously been proposed in the general
      multi-category classification problem but the definition of ROC surfaces here is
      less complex and addresses directly the narrower problem of ordered categories in
      the three-class and, by extension, the multi-class problem applied to continuous
      and ordinal data. Non-parametric manipulation of both continuous and discrete
      test data and comparison between two diagnostic tests applied to the same
      subjects are considered. A three-group classification example in the context of
      HIV neurological disease is presented and the results are discussed.

PMID- 15505887
TI  - Reconsidering the odds ratio as a measure of 2 x 2 association in a population.

PMID- 15505888
TI  - Conditional mixed models adjusting for non-ignorable drop-out with administrative
      censoring in longitudinal studies.
AB  - In this paper, a class of conditional mixed models is proposed to adjust for non
      ignorable drop-out, while also accommodating unequal follow-up due to staggered
      entry and administrative censoring in longitudinal studies. Conditional linear
      and quadratic models which model subject-specific slopes as linear or quadratic
      functions of the time-to-drop-out, as well as pattern mixture models are both
      special cases of this approach. We illustrate these models and compare them with
      the usual maximum likelihood approach assuming ignorable drop-out using data from
      a multi-centre randomized clinical trial of renal disease. Simulations under
      various scenarios where the drop-out mechanism is ignorable and non-ignorable are
      employed to evaluate the performance of these models.

PMID- 15505890
TI  - Chronic disease prevention: public health potential and research needs.
AB  - This paper, arising out of an event to honour the statistical and scientific
      contributions of Professor Peter Armitage, is concerned with research strategies
      and needs for chronic disease prevention. A few highlights from recent
      intervention trials for the prevention of cancer, cardiovascular disease,
      fractures and diabetes is provided, along with a discussion of some settings
      where intervention trial results seem discrepant with a body of preceding
      observational data. This background is used to identify research strategies and
      infrastructure needs for moving this vitally important research area forward, for
      both chemoprevention and lifestyle modification interventions.

PMID- 15505891
TI  - Estimating trends and seasonality in coronary heart disease.
AB  - We present two methods of estimating the trend, seasonality and noise in time
      series of coronary heart disease events. In contrast to previous work we use a
      non-linear trend, allow multiple seasonal components, and carefully examine the
      residuals from the fitted model. We show the importance of estimating these three
      aspects of the observed data to aid insight of the underlying process, although
      our major focus is on the seasonal components. For one method we allow the
      seasonal effects to vary over time and show how this helps the understanding of
      the association between coronary heart disease and varying temperature patterns.

PMID- 15505892
TI  - A Bayesian MCMC approach to study transmission of influenza: application to
      household longitudinal data.
AB  - We propose a transmission model to estimate the main characteristics of influenza
      transmission in households. The model details the risks of infection in the
      household and in the community at the individual scale. Heterogeneity among
      subjects is investigated considering both individual susceptibility and
      infectiousness. The model was applied to a data set consisting of the follow-up
      of influenza symptoms in 334 households during 15 days after an index case
      visited a general practitioner with virologically confirmed influenza. Estimating
      the parameters of the transmission model was challenging because a large part of
      the infectious process was not observed: only the dates when new cases were
      detected were observed. For each case, the data were augmented with the
      unobserved dates of the start and the end of the infectious period. The
      transmission model was included in a 3-levels hierarchical structure: (i) the
      observation level ensured that the augmented data were consistent with the
      observed data, (ii) the transmission level described the underlying epidemic
      process, (iii) the prior level specified the distribution of the parameters. From
      a Bayesian perspective, the joint posterior distribution of model parameters and
      augmented data was explored by Markov chain Monte Carlo (MCMC) sampling. The mean
      duration of influenza infectious period was estimated at 3.8 days (95 per cent
      credible interval, 95 per cent CI [3.1,4.6]) with a standard deviation of 2.0
      days (95 per cent CI [1.1,2.8]). The instantaneous risk of influenza transmission
      between an infective and a susceptible within a household was found to decrease
      with the size of the household, and established at 0.32 person day(-1) (95 per
      cent CI [0.26,0.39]); the instantaneous risk of infection from the community was
      0.0056 day(-1) (95 per cent CI [0.0029,0.0087]). Focusing on the differences in
      transmission between children (less than 15 years old) and adults, we estimated
      that the former were more likely to transmit than adults (posterior probability
      larger than 99 per cent), but that the mean duration of the infectious period was
      similar in children (3.6 days, 95 per cent CI [2.3,5.2]) and adults (3.9 days, 95
      per cent CI [3.2,4.9]). The posterior probability that children had a larger
      community risk was 76 per cent and the posterior probability that they were more
      susceptible than adults was 79 per cent.

PMID- 15505893
TI  - Comparison of Bayesian model averaging and stepwise methods for model selection
      in logistic regression.
AB  - Logistic regression is the standard method for assessing predictors of diseases.
      In logistic regression analyses, a stepwise strategy is often adopted to choose a
      subset of variables. Inference about the predictors is then made based on the
      chosen model constructed of only those variables retained in that model. This
      method subsequently ignores both the variables not selected by the procedure, and
      the uncertainty due to the variable selection procedure. This limitation may be
      addressed by adopting a Bayesian model averaging approach, which selects a number
      of all possible such models, and uses the posterior probabilities of these models
      to perform all inferences and predictions. This study compares the Bayesian model
      averaging approach with the stepwise procedures for selection of predictor
      variables in logistic regression using simulated data sets and the Framingham
      Heart Study data. The results show that in most cases Bayesian model averaging
      selects the correct model and out-performs stepwise approaches at predicting an
      event of interest.

PMID- 15505894
TI  - Estonian efficiency.

PMID- 15505895
TI  - Maurice H F Wilkins.

PMID- 15505896
TI  - Quantitative histology by multicolor slide-based cytometry.
AB  - BACKGROUND: In lymphatic organs, the quantitative analysis of the spatial
      distribution of leukocytes by tissue cytometry would give relevant information
      about altercations during diseases (leukemia, HIV, AIDS) and their therapeutic
      regime, as well as in experimental settings. METHODS: We have developed a
      semiautomated analysis method for laser scanning cytometry (LSC) termed "multiple
      thresholding," which is suitable for archived or fresh biopsy material of human
      lymph nodes and tonsils. Sections are stained with PI for nuclear DNA and up to
      four antigens using direct and indirect immunofluorescence (argon laser, Ar) or
      on specific cell labeling. Due to the heterogeneity of cell density, measurements
      are performed repeatedly at different threshold levels (low threshold: regions of
      low cellular density, germinal center; high threshold: dense regions, mantle
      zone). Data are acquired by single-(Ar) or dual-laser excitation (Ar-HeNe) in
      order to analyze single-(FITC) up to fourcolor (FITC/PE/PECy5/APC) stained
      specimen. RESULTS: Percentage and cellular density of cell-subsets is quantified
      in different microanatomical regions of the specimen. These data were highly
      correlated with manual scoring a identical specimens (r(2) = 0.96, P < 0.0001).
      With LSC, semiautomated operator-independent immunophenotyping in tissue sections
      of lymphatic organs with up to three antibodies simultaneously is possible.
      CONCLUSIONS: We expect this tissue cytometric approach to yield new insight into
      processes during diseases and help to quantify the success of therapeutic
      interventions.

PMID- 15505897
TI  - Obituary. Andrew P. Somlyo (1930-2004).

PMID- 15505899
TI  - Abstracts of the 7th International Conference of Anticancer Research. October 25
      30, 2004, Corfu, Greece.

PMID- 15505901
TI  - [History of orthodontics: education, publications, professional organizations in
      the first half of the XX century].

PMID- 15505900
TI  - [Allergy to metals used in orthodontics and methods for its diagnosis].

PMID- 15505903
TI  - [Abstracts of the XXXIV Congress of the Spanish Nephrology Society. Tenerife,
      Spain, 2-5 October 2004].

PMID- 15505902
TI  - Abstracts of the 12th World Congress of Psychophysiology: The Olympics of the
      Brain. Thessaloniki, Greece. September 18-23, 2004.

PMID- 15505904
TI  - Abstracts of the British Pharmaceutical Conference. Manchester, United Kingdom,
      September 27-29, 2004.

PMID- 15505905
TI  - European Academy of Childhood Disability Annual Meeting. 7-9 October 2004,
      Edinburgh, Scotland. Abstracts.

PMID- 15505906
TI  - Presentation of the 2003 NASPGHAN Harry Shwachman Award to Dr. Peter R. Durie.

PMID- 15505907
TI  - Presentation of the 2003 NASPGHAN Distinguished Service Award to Dr. Joseph
      Fitzgerald.

PMID- 15505908
TI  - Bibliography. Current world literature. Prevention.

PMID- 15505910
TI  - Abstracts of the 9th Central European Lung Cancer Conference. Gdansk, Poland,
      September 23-25, 2004.

PMID- 15505909
TI  - Presentation of the 2003 AAP Murray Davidson Award to Dr. William K. Schubert.

PMID- 15505911
TI  - [Abstracts of the 6th Annual Meeting of the Austrian Society of Endocrinology and
      Metabolism. St Wolfgang, 19-20 April 2001].

PMID- 15505912
TI  - Abstracts of the 7th Annual Meeting of the Austrian Society of Endocrinology and
      Metabolism. St Wolfgang, 25-27 April 2002.

PMID- 15505913
TI  - Regulating bioethics with judge-made law: the American experience.

PMID- 15505914
TI  - Do judges make (a better) law? The French experience.

PMID- 15505915
TI  - Scientific process, judge-made law and procedural law.

PMID- 15505916
TI  - Abstracts of the International Conference on Gender and Health: Realizing a
      Gender Sensitive Health Care System. September 16-18, 2002, Vienna, Austria.

PMID- 15505917
TI  - The limiting factor. Biotechnology and the charter for an international science
      and technology reference court.

PMID- 15505918
TI  - Genetics research and the judicial decisions.

PMID- 15505919
TI  - Genetics and law: a challenge for lawyers and judges in the new millennium.

PMID- 15505920
TI  - Nutrition and hydration in PVS individuals: the Cruzan, Bland and Englaro cases.

PMID- 15505921
TI  - Termination of life support measures in case of persons in permanent vegetative
      state.

PMID- 15505922
TI  - [Abstracts of the 29th Meeting of the Austrian Society of Urology and Andrology.
      12-14 June 2003, Vienna, Austria].

PMID- 15505923
TI  - Ad hoc committee on artificial nutrition and hydration of individuals in a
      permanent vegetative state report.

PMID- 15505924
TI  - [Conducting high quality randomized controlled clinical trial].

PMID- 15505925
TI  - Abstracts of the 1st European Conference on Tumor Angiogenesis and Antiangiogenic
      Therapy. Munich, Germany, 1-3 October 2004.

PMID- 15505926
TI  - Abstracts of the Inflammation Research Association 12th International Conference.
      October 3-7, 2004, Bolton Landing, New York, USA.

PMID- 15505927
TI  - Abstracts of the Summer Meeting of the British Association for
      Psychopharmacology. 25-28 July 2004, Harrogate, United Kingdom.

PMID- 15505928
TI  - Abstracts from the 24th Annual Meeting of the National Academy of
      Neuropsychology. November 17-20, 2004, Seattle, Washington, USA.

PMID- 15505929
TI  - Annual Report on Findings of Infectious Agents in Japan, 2000.

PMID- 15505930
TI  - Abstracts of the 6th International Symposium on NeuroVirology and the HIV
      Neuroprotection Workshop. 10-14 September 2004. Sardinia, Italy.

PMID- 15505931
TI  - Associations between CYP11B2 gene -344T/C polymorphism and essential hypertension
      in the Han nationality in Shandong province.
AB  - OBJECTIVE: To investigate whether the -344T/C polymorphism of CYP11B2 gene is
      associated with essential hypertension in the Hans in Shandong province. METHODS:
      Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were
      measured with radioimmunoassays; the hypertensives were classified as low-renin
      and normal- or high-renin group by PAC/PRA ratio. -344T/C polymorphism was
      determined by polymerase chain reaction-restricted fragment length polymorphism
      (PCR-RFLP) in controls and hypertensives. RESULTS: No significant differences
      were found in genotype distribution or allele frequency between groups of control
      and primary hypertension or between groups of control and normal- or high-renin
      hypertension. The C allele frequency in low-renin hypertension group was
      significantly higher than that in normotensives and normal- or high-renin
      hypertension group (P < 0.05). CONCLUSION: These results suggest that -344T/C
      polymorphism of CYP11B2 gene may be associated with low-renin essential
      hypertension in the Han nationality in Shandong province.

PMID- 15505932
TI  - Everyone should watch glycosated hemoglobin and blood sugar levels, not just
      diabetics, research says.

PMID- 15505933
TI  - Study demonstrates effectiveness of new model of pediatric asthma care.

PMID- 15505934
TI  - New risk model may help determine better treatment for glaucoma.

PMID- 15505935
TI  - Government cholesterol recommendations questioned.

PMID- 15505936
TI  - [Abstracts of the XXI Congress of the French Society of Endocrinology. Reims,
      France, 29 September-2 October 2004].

PMID- 15505937
TI  - Abstracts of the 26th Annual Meeting of the American Society for Bone and Mineral
      Research. October 1-5, 2004, Seattle, Washington, USA.

PMID- 15505938
TI  - Rural health: a personal perspective.

PMID- 15505939
TI  - Team nursing improves staff morale, patient care.

PMID- 15505940
TI  - Medical discipline--professional misconduct.

PMID- 15505941
TI  - Detection and selection decisions in the practice of screening mammography.

PMID- 15505942
TI  - A meta-analysis of single-subject-design intervention research for students with
      LD.
AB  - This article summarizes single-subject-design intervention studies that include
      students with learning disabilities. Effect sizes of 85 studies were analyzed
      across instructional domains (e.g., reading, mathematics); sample characteristics
      (e.g., age, intelligence); intervention parameters (e.g., number of instructional
      sessions, instructional components); and methodological procedures (e.g.,
      internal validity, treatment integrity, sample representation). The major
      findings were as follows: (a) All domain areas except handwriting yielded effect
      sizes at or above Cohen's .80 threshold for a substantial finding; (b)
      instructional components related to drill-repetition-practice-review,
      segmentation, small interactive groups, and the implementation of cues to use
      strategies contributed significant variance (15%) to estimates of effect size;
      (c) strategy instruction (SI) models better predicted effect size estimates than
      direct instruction (DI) models when the results were qualified by the reported
      intellectual and reading levels of the participants; (d) high-IQ discrepancy
      groups yielded lower effect sizes compared to low-IQ discrepancy groups in the
      domain of reading, whereas the reverse effect occurred when treatment outcomes
      were not reading measures; and (e) the low-IQ discrepancy groups yielded higher
      effect sizes for a Combined DI and SI Model when compared to competing models.
      The results are supportive of the pervasive influence of cognitive strategy and
      direct instruction models across treatment domains and of the notion that
      variations in sample definition moderate treatment outcomes.

PMID- 15505944
TI  - Albert Einstein and LD: an evaluation of the evidence.
AB  - Historical figures suspected of having learning disabilities are often subjected
      to retrospective diagnoses. One such figure is Albert Einstein. Several
      organizations that promote the interests of individuals with learning
      disabilities claim that Einstein had a learning disability. A review of
      biographical sources, however, provides little or no evidence to support this
      claim. The claim derives its force not from evidence but from a powerful belief-
      that the greatest among us suffer from some impairment--and from an equally
      powerful desire to enhance the status of a marginalized group by including within
      it exceptional individuals.

PMID- 15505945
TI  - Meeting the evolving education needs of faculty in providing access for college
      students with LD.
AB  - Faculty play an essential role in providing access for college students with LD.
      Though many recommendations exist in the literature for educating faculty about
      their roles regarding students with LD, it is unclear whether these strategies
      are actually addressing faculty needs. To examine this issue, the evolving role
      of faculty is discussed. Current practices in faculty education pertaining to
      college students with LD are reviewed. Discrepancies between the evolving faculty
      role and current faculty education practices are examined. Guiding questions are
      proposed for expanding faculty education efforts and models to keep pace with the
      evolving faculty role in providing access for college students with LD.

PMID- 15505943
TI  - Neuropsychological intervention in dyslexia: two studies on British pupils.
AB  - The theoretical context of this research is developmental neuropsychology--in
      particular, the educational implications for the classification of and
      intervention in specific developmental dyslexia (SDD). Controlled and validated
      research can help identify optimal teaching methods for groups and individuals.
      Within this framework, neuropsychological theory can be explored as a medium for
      improving intervention for pupils with SDD. Neuropsychological stimulation cannot
      change the macro aspects of the brain but can change its "finetuning" and its
      response to written text. Within the psycho-neurological approaches, Bakker
      (1979, 1990, 1998) developed both a diagnostic procedure and empirically
      investigated intervention procedures. The theory rests on the Balance Model of
      learning to read, in which differential hemisphere involvement is implicated in
      beginning and advanced reading. Intervention can take place via hemisphere
      specific stimulation using visual or tactile stimulation or hemisphere-alluding
      stimulation using modified text. Two investigations are presented, one
      experimental and another clinical. The results support the validity of dyslexia
      subtyping and the effectiveness of the treatment methods.

PMID- 15505946
TI  - Characteristic behaviors of students with LD who have teacher-identified math
      weaknesses.
AB  - Mathematics learning disabilities (LD) have gained increased attention over the
      last decade from both researchers and practitioners. A large percentage of
      students receiving learning disability services experience difficulties with
      mathematics, but little research has examined the specific mathematics behaviors
      of students with LD who have teacher-identified math weaknesses. This study
      examines the literature on mathematics LD and identifies specific behaviors from
      that body of research for the purpose of determining the extent to which those
      behaviors are observed in students with LD. Data are presented from observations
      of 391 special education professionals on 1724 students with LD, 870 of whom had
      identified math weaknesses and 854 of whom did not. Our results validate the
      existing literature and provide implications for teachers, researchers, and
      others interested in studying mathematics LD.

PMID- 15505947
TI  - Comorbidity of reading disability and attention-deficit/hyperactivity disorder:
      differences by gender and subtype.
AB  - This study used a community sample of 494 twins with a reading disability (223
      girls, 271 boys) and 373 twins without a reading disability (189 girls, 184 boys)
      to assess the relation between reading disability (RD) and attention
      deficit/hyperactivity disorder (ADHD). Symptoms of DSM-III and DSM-IV ADHD were
      classified into symptoms of inattention and symptoms of hyperactivity-impulsivity
      (H/I). Results indicated that individuals with RD were more likely than
      individuals without RD to meet criteria for ADHD and that the association between
      RD and ADHD was stronger for symptoms of inattention than for symptoms of H/I.
      Parents and teachers reported similar rates of ADHD, suggesting that ADHD
      symptoms were pervasive across settings and were not solely attributable to
      academic frustration. Analyses of possible gender differences revealed that RD
      was significantly associated with inattention in both girls and boys but
      associated with H/I only in boys. This difference may provide a partial
      explanation for the discrepancy between the gender ratio obtained in referred
      (approximately 4 boys to 1 girl) and nonreferred (1.2 to 1.5 boys to 1 girl)
      samples of individuals with RD. Specifically, the hyperactive and impulsive
      behaviors exhibited by boys with RD may be more disruptive than the inattentive
      behaviors exhibited by girls and may therefore precipitate more frequent
      referrals for clinical attention.

PMID- 15505949
TI  - Utility of kindergarten teacher judgments in identifying early learning problems.
AB  - Most existing research on early identification of learning difficulties has
      examined the validity of methods for predicting future academic problems. The
      present study focused instead on the sensitivity of kindergarten teachers to
      learning problems in their students and on the continuity of teacher-identified
      problems over time. To identify early learning problems, kindergarten teachers in
      a suburban school district rated student progress toward six academic objectives
      as satisfactory or unsatisfactory. Twenty percent of the district's 303
      kindergarten children received unsatisfactory ratings in at least one area.
      Thirty-eight of these children (identified group) were matched to 34 children
      with satisfactory ratings in all areas (nonidentified group). Results of testing
      conducted during kindergarten revealed poorer academic achievement in identified
      children than in nonidentified children. Children from the identified group also
      performed more poorly than children from the nonidentified group on tests of
      phonological processing and working memory/executive function and were rated by
      teachers as having more behavior and attention problems and lower social
      competence. Follow-up of the sample to first grade documented continued learning
      problems in the identified group. These findings support the use of teacher
      judgements in early detection of learning problems and argue against reliance on
      discrepancy criteria.

PMID- 15505948
TI  - Differential genetic etiology of reading disability as a function of IQ.
AB  - To test the hypothesis that the genetic etiology of reading disability differs as
      a function of IQ, composite reading performance data from 223 pairs of identical
      twins and 169 pairs of same-gender fraternal twins in which at least one member
      of each pair was classified with reading disability were subjected to multiple
      regression analysis (DeFries & Fulker, 1985, 1988). In the total sample,
      heritability of the group deficit in reading performance (h(g)2) was .58 (+/-
      .08). However, when the basic regression model was fitted separately to data from
      twin pairs with average Wechsler (1974, 1981) full scale IQ scores below 100 or
      100 and above, resulting estimates of h(g)2 were .43 and .72, respectively, a
      significant difference (p < or = .03, one-tailed). The results of fitting
      extended regression models to reading performance and continuous IQ data provide
      evidence that the genetic etiology of reading disability differs as a linear
      function of IQ (p < or = .007, one-tailed). These results suggest that IQ is
      relevant for the diagnosis of reading disability and that environmental
      influences may be more salient as a cause of reading difficulties in children
      with lower IQ scores.

PMID- 15505950
TI  - Influence of affect on social-information processing.

PMID- 15505951
TI  - Definition and documentation: theory, measurement, and the courts.
AB  - Definition of terms and the selection criteria for operationalizing the standard
      of disability are critical to accessing accommodations. The purpose of this
      article was to examine the research surrounding definitiorns and selection
      criteria for learning disabilities and attention-deficit/hyperactivity disorder
      at the postsecondary level. Implications from and for the courts follow a
      critical analysis of the professional literature. The need for researchers to
      utilize theory-based models to investigate the multivariate relationships between
      and within constructs underlying current definitions and eligibility criteria is
      also disscussed.

PMID- 15505952
TI  - Evaluation practices for college students with LD.
AB  - To examine current practices in the use of psychoeducational evaluations for
      service delivery, we surveyed 91 service providers to college students with
      learning disabilities. The three purposes of the survey were to determine (a)
      whether service delivery decisions are based on information from
      psychoeducational evaluations, (b) which sections of the psychoeducational report
      are most useful in making service delivery decisions, and (c) the respondents'
      satisfaction with the tests and measurements for service delivery. The findings
      supported the common belief that data from psychoeducational evaluations serve as
      the primary basis for both eligibility and specific accommodation determinations.
      Respondents reported that all sections of the psychoeducational evaluation
      written report were useful, with the least useful section being test scores and
      the most useful being the summary of cognitive strengths and weaknesses. However,
      the section used most often for service delivery decisions was the professional's
      recommendations.

PMID- 15505953
TI  - Faculty members' provision of instructional accommodations to students with LD.
AB  - The existing research on the instructional accommodation process of college
      students with learning disabilities focuses on attitudes and theoretical models
      without delineating actual practices. To date, the discussion of facilitating
      factors and barriers to this process has been broad and lacking specificity.
      Surveys were mailed to 485 faculty members at the University of Massachusetts,
      Amherst, who received an instructional accommodation form from the office of
      Learning Disabilities Support Services in the fall of 1995. The survey focused on
      faculty members' reported degree of ease or difficulty in implementing
      instructional accommodations, their perceptions regarding adequacy of support,
      and their own beliefs and understandings concerning the need for and benefit of
      providing instructional accommodations. The results indicate that beliefs about
      the helpfulness of and need for instructional accommodations were associated with
      the provision of the accommodations. Also, a perception of support from the
      University influenced the ease of providing instructional accommodations. A
      significant difference was found between the behavior of tenure-track faculty and
      non-tenure-track faculty.

PMID- 15505954
TI  - Adolescents with and without LD make the transition to middle school.
AB  - The purpose of this 2-year study was to describe how Hispanic students with and
      without learning disabilities fared academically and socially during the
      transition from elementary school to middle school. Participants were 14 Hispanic
      students who were instructed in a sixth-grade consultation/collaboration,
      inclusive elementary classroom before making the transition to middle school.
      Examination of social, academic, and student perception data revealed that, on
      the whole, the students with learning disabilities and those without experienced
      the transition similarly and fared well during the elementary-to-middle-school
      transition.

PMID- 15505955
TI  - Word identification and reading disorders in the Spanish language.
AB  - In this study, a reading-level-match design was used to test the hypothesis that
      children with reading disability (RD) are characterized by poor phonological
      skills, and that a developmental lag, as opposed to a specific deficit, will be
      found in transparent orthographies. Spanish has a transparent orthography and
      thus children with RD should not show severe difficulties in the use of the
      phonological route, as in the English language. A sample of 118 participants was
      selected and organized into three different groups: 40 with RD, 38 normal readers
      matched in age with the former, and 40 younger normal readers at the same reading
      level as those with RD. Two experiments were conducted to investigate the effects
      of lexicality, word frequency, word length, and positional frequency of syllables
      on lexical decision making and word-naming performance. While the participants
      were performing the naming task, we recorded what they read to subsequently
      analyze the form as well as the frequency of naming errors. The present study
      provides evidence for a deficit in phonological processing in a transparent
      orthography, particularly in nonword reading, because there were differences
      between the reading-level-matched groups.

PMID- 15505956
TI  - Profiles of Asian American students with LD at initial referral, assessment, and
      placement in special education.
AB  - Alhough Asian American students are underrepresented in special education, recent
      studies have highlighted concerns about the cultural and linguistic
      appropriateness of the identification and placement process. This study examined
      the characteristics of Asian American elementary students with learning
      disabilities (LD) in a school district in the Southwest that was selected because
      it served the largest number of Asian American students with LD in the state. Due
      to the small numbers of students served, the sample included all Asian American
      students with LD in Grades K to 5 (N = 26). Variables of interest included
      students' demographic characteristics, factors associated with referral,
      assessment practices and student profiles, and instructional recommendations for
      special education services. The results suggest that the experiences of Asian
      American students with LD are similar to those of Mexican American students with
      LD reported in earlier studies. These findings also reflect the challenges faced
      by educators in providing appropriate educational services for language minority
      students.

PMID- 15505957
TI  - Factor structures of Taiwanese teachers' ratings of ADHD: a comparison with U.S.
      studies.
AB  - The purpose of this study was to compare factor structures from Taiwanese
      teachers' ratings with diagnostic definitions of attention-deficit/hyperactivity
      disorder (ADHD) as described in the DSM-III-R, DSM-IV, and ICD-10; to examine how
      factor structures of Taiwanese teachers' ratings of ADHD symptoms compare with
      factor structures reported in research using school-based American participants;
      and to examine gender differences. One hundred and twenty-one homeroom teachers
      from six public elementary schools in Taipei County, Taiwan, rated two boys and
      two girls randomly selected from their homerooms using the ADHD checklist.
      Findings from this study support the concurrent validity of the DSM-IV ADHD
      factor structures of hyperactivity-impulsivity and inattention. Comparability of
      these findings with school-based U.S. studies suggests the cross-cultural
      congruency of behaviors associated with ADHD.

PMID- 15505958
TI  - Right hemisphere dysfunction in ADHD: visual hemispatial inattention and clinical
      subtype.
AB  - The relationship between right hemisphere dysfunction and attention
      deficit/hyperactivity disorder (ADHD) remains controversial. We administered a
      random letter cancellation test to 58 carefully selected adult patients meeting
      DSM-IV criteria for ADHD and 29 age- and education-matched controls. Patients
      with ADHD had a higher mean omission rate on the left side than the controls, and
      a greater percentage of ADHD patients than controls made more omissions on the
      left than on the right (L > R errors). ADHD patients who made L > R errors had
      lower performance IQ scores than ADHD patients who did not make L > R errors.
      However, ADHD patients who made L > R errors did not differ from ADHD patients
      who did not make L > R errors in ADHD subtype, medication response, or
      neuropsychological measures of attention, executive function, verbal memory,
      nonverbal memory, or academic achievement. Patients without a family history of
      ADHD were more likely to make L > R errors than patients with a family history of
      ADHD. This study provides support for the concept of right hemisphere dysfunction
      in a subset of patients with ADHD. However, ADHD patients who make L > R errors
      do not appear to represent a distinct clinical subgroup in terms of medication
      response, ADHD subtype, or neuropsychological test performance.

PMID- 15505959
TI  - Reciprocal teaching of social studies in inclusive elementary classrooms.
AB  - Reading comprehension relies on the use of metacognitive strategies. Reciprocal
      teaching has been found to be an effective comprehension technique to use with
      students with learning disabilities. This study examined the effectiveness of
      reciprocal teaching during social studies instruction with several students with
      learning disabilities in fourth-, fifth-, and sixth-grade inclusive classrooms.
      One hundred and twenty-eight students in Grades 4, 5, and 6 participated. Four
      comprehension assessments were administered, as well as an external measure and
      30-day maintenance assessment. A mixed-design MANOVA was used to determine
      interaction on three reading comprehension measures. Results indicated that all
      students improved their performance on comprehension measures compared with
      students in the control groups. Improvement continued to be displayed after 30
      days in both the sixth and the fourth grades. Students with learning disabilities
      significantly improved their ability to compose summaries compared to the control
      students.

PMID- 15505960
TI  - RE: LD and delinquency: rethinking the "link".

PMID- 15505961
TI  - RE: LD and delinquency: rethinking the "link".

PMID- 15505962
TI  - Differentiating between difficult-to-remediate and readily remediated poor
      readers: more evidence against the IQ-achievement discrepancy definition of
      reading disability.
AB  - In this article we discuss research bearing on the traditional use of the IQ
      achievement discrepancy to define specific reading disability. We initially
      review the evidence presented by Rutter and Yule (1975) in support of this
      practice, and then discuss results from subsequent studies that have questioned
      the reliability of their findings. We also discuss results from more recent
      studies demonstrating that the IQ-achievement discrepancy does not reliably
      distinguish poor from normal readers, whereas language-based measures do reliably
      distinguish these groups. We highlight results from a study we recently
      completed, in which it was found that IQ scores did not differentiate between
      poor readers who were found to be readily remediated and poor readers who were
      difficult to remediate. In view of the convergent evidence against the use of IQ
      scores to define specific reading disability, we suggest that the IQ-achievement
      discrepancy definition of this disorder be discarded.

PMID- 15505963
TI  - What definitions of learning disability say and don't say: a critical analysis.
AB  - In this article, we analyze critically available definitions of learning
      disability (LD). The general problem of definition is discussed first followed by
      a discussion of individual LD definitions from the earliest to the latest. We
      conclude that LD definitions fail to provide substantive insight into the nature
      of the condition. The reasons for this failure are discussed in relation to the
      nature of definition and the difficulties in providing operational definitions of
      LD that are meaningful and significant. Finally, means for resolving the problem
      of definition are discussed.

PMID- 15505964
TI  - A comparison of two reading interventions for children with reading disabilities.
AB  - This study compared the effectiveness of two reading interventions in a public
      school setting. Forty-five second-grade children with reading disabilities were
      randomly assigned to a 6-week phonological awareness, word analogy, or math
      training program. The two reading interventions differed from each other in (a)
      the unit of word analysis (phoneme versus onset-rime), (b) the approach to
      intervention (contextualized versus decontextualized), and (c) the primary domain
      of reading instruction (oral versus written language). Results indicate that
      children in both reading programs achieved significant gains in beginning reading
      skills, learning the specific skills taught in their respective programs, and
      applying what they had learned to uninstructed material on several transfer-of
      learning measures, in comparison to children in the control group. For children
      in both reading intervention groups, the most significant mediator of growth in
      oral reading fluency was a child's initial level of word identification skill.
      Implications of these findings are that systematic, high quality reading
      intervention can occur in a small group, public school setting and that there are
      several different paths to the remediation of children with reading disabilities.

PMID- 15505965
TI  - Treatment of specific developmental reading disorders, derived from single- and
      dual-route models.
AB  - A group of 21 participants with specific reading disorders was treated with a
      method derived from dual-route models and another group of 23 with a method
      derived from single-route models of reading. Both treatments were compared with
      four control treatments. The reading performance of each participant was compared
      with that of his or her chronological-age controls on the following variables:
      speed and accuracy of reading passage, isolated words and nonwords, and accuracy
      in homophone recognition. The treatment deriving from dual-route models produced
      significant improvements in the homophone recognition, compared to all other
      treatments. The treatment deriving from single-route models produced significant
      improvements, compared to all other treatments, in speed of word reading.
      Furthermore, these two treatments produced significant improvement with respect
      to all other treatments but one, in speed of nonword reading. These findings
      support the hypothesis that treatments derived from specific models of reading
      development are superior to other treatments. However the benefits obtained on
      the reading of isolated stimuli (words, homophones) did not significantly improve
      the reading of a passage. This fact suggests that treatments should include
      exercises involving passages or sentences.

PMID- 15505966
TI  - Reliability and validity of the adult reading history questionnaire.
AB  - The reliability and validity of a revised version of Finucci's (1982) Reading
      History Questionnaire was examined in two adult samples. One sample included 84
      adults from an ongoing study of familial dyslexia, and a second sample was
      composed of parents of 107 children from a longitudinal study of reading
      development. Internal consistency was demonstrated by Cronbach's alphas of .94
      and .92 in the two samples. Test-retest reliability was demonstrated by
      significant correlations (.87 and .84 in the two samples) over several years
      between an earlier and revised form of the questionnaire. Validity was
      demonstrated via (a) correlations between the questionnaire score and reading
      measures (rs = .57-.70), (b) the results of a discriminant function analysis that
      used questionnaire scores to predict reading disability diagnosis, and (c) the
      finding that the questionnaire had substantial incremental validity in predicting
      reading skill in a hierarchical regression analysis that first entered IQ and
      SES. These results indicated that the questionnaire is both reliable and valid.

PMID- 15505967
TI  - ADHD and reading disabilities: a cluster analytic approach for distinguishing
      subgroups.
AB  - Data suggest that children with reading disability (RD) and non-RD children with
      attention-deficit/hyperactivity disorder (ADHD) may comprise distinct subgroups.
      Research has been hampered by variance in definitional criteria, which results in
      the study of different subgroups of children. Using cluster analysis, this study
      empirically divided children with ADHD (N = 54), based on their Full Scale IQ
      (FSIQ) and reading ability. Four distinct subgroups emerged in which cognitive,
      behavioral, and neurochemical function was compared. Cluster 1 was of average
      FSIQ and reading scores; Cluster 2 was of average FSIQ but showed impairment in
      reading; Cluster 3 had high FSIQ and reading scores; and Cluster 4 had low scores
      in both domains. The groups had different patterns of cognitive, behavioral, and
      neurochemical function, as determined by discrepancies in Verbal-Performance IQ,
      academic achievement scores, parent aggression ratings, and a measure of
      noradrenergic function. These distinctions are discussed with regard to etiology,
      treatment, and long-term outcome.

PMID- 15505968
TI  - Neuroimaging of higher cognitive function.

PMID- 15505969
TI  - Neuroimaging of performance monitoring: error detection and beyond.
AB  - The ability to monitor performance and behavior is crucial for goal-directed,
      adaptive behavior in a changing environment. Performance monitoring has been
      extensively investigated using behavioral, electrophysiological and hemodynamic
      measures, and is still in the focus of many research projects. This paper gives
      an overview on neuroimaging of performance monitoring and the models which arose
      from several research approaches, taking into account the knowledge stemming from
      electrophysiological and lesion studies. Particular emphasis is put on error
      detection and response conflict monitoring, but also at motivational factors.
      Furthermore, the paper presents and discusses data from an fMRI study
      investigating the influence of error relevance on the hemodynamic correlates of
      error processing. By instruction and financial reward manipulation, the relevance
      of errors were block-wise modulated in a flanker paradigm. The results suggest
      that the engagement of the posterior frontomedian wall (pFMC) previously shown to
      be involved in performance monitoring is dependent on error relevance.

PMID- 15505970
TI  - The effects of vagus nerve stimulation on decision-making.
AB  - Subcortical and brainstem structures are increasingly becoming recognized as
      important contributors to higher cognitive functioning. Decision-making is one
      such function, particularly as viewed within the framework of the somatic marker
      hypothesis (SMH). The SMH views the participation in decision-making by the body
      proper as integral to emotional biasing and hence key to choosing in an
      advantageous manner. This study focuses on the vagus nerves as a possible conduit
      for somatic afferent signals pertinent to decision-making. We tested eight
      epileptic patients with implanted left vagus nerve stimulators. To assess
      decision-making we used the gambling task, which is sensitive to real-life
      decision-making deficits. Using a counterbalanced design, each participant
      performed the gambling task under a condition in which low-level vagus nerve
      stimulation (VNS) was covertly delivered, and another condition in which no VNS
      was delivered. Participants showed improved performance, that is, made more
      advantageous choices, in the stimulated relative to the unstimulated condition.
      Although these results should be viewed as preliminary, they suggest that the
      vagus nerve is a conduit for afferent somatic signals that can influence decision
      making.

PMID- 15505971
TI  - The neural basis of conditional reasoning with arbitrary content.
AB  - Behavioral predictions about reasoning have usually contrasted two accounts,
      Mental Logic and Mental Models. Neuroimaging techniques have been providing new
      measures that transcend this debate. We tested a hypothesis from Goel and Dolan
      (2003) that predicts neural activity predominantly in a left parietal-frontal
      system when participants reason with arbitrary (non-meaningful) materials. In an
      event-related fMRI investigation, we employed propositional syllogisms, the
      majority of which involved conditional reasoning. While investigating conditional
      reasoning generally, we ultimately focused on the neural activity linked to the
      two valid conditional forms--Modus Ponens (If p then q; p//q) and Modus Tollens
      (If p then q; not-q//not-p). Consistent with Goel and Dolan (2003), we found a
      left lateralized parietal frontal network for both inference forms with
      increasing activation when reasoning becomes more challenging by way of Modus
      Tollens. These findings show that the previous findings with more complex
      Aristotlean syllogisms are robust and cast doubt upon accounts of reasoning that
      accord primary inferential processes uniquely to either the right hemisphere or
      to language areas.

PMID- 15505972
TI  - Neural basis of spontaneous thought processes.
AB  - Studies examining thought processes have focused upon the deliberate, goal
      directed mental processes occurring during complex cognitive tasks. Spontaneously
      occurring thought processes have, on the other hand, received much less
      attention. Such spontaneous thought processes occur frequently when no task is
      present or when task demands are low. Although their existence has been
      recognised, their study has been difficult due to lack of direct behavioural
      measures. Nevertheless, a number of behavioural methods based on subjects' verbal
      reports have been developed. Findings derived using such behavioural methods
      suggest that spontaneous thought processes share common cognitive mechanisms with
      purposeful, task-related thought processes. Furthermore, evidence from
      neuroimaging observations is accumulating suggesting similar conclusions about
      the neural basis of spontaneous thought processes. These neuroimaging findings
      demonstrate an overlap in the pattern of activation between various cognitive
      tasks and rest, with a number of higher cortical regions activated in common,
      including visual areas, medial temporal lobe, and lateral cortical association
      areas. Many of these observations have, however, been based upon comparisons
      between rest and tasks posing relatively high cognitive demands. In contrast,
      here we report an fMRI study in which rest was compared to a simple left/right
      response task of minimal cognitive demands. Rest was associated with greater
      activation in temporopolar cortex, parahippocampus, rostrolateral prefrontal
      cortex, parietal and visual cortical areas. Activation of temporal lobe
      structures was particularly extensive and robust, suggesting that long-term
      memory processes may form the core of spontaneous thought. By considering such
      long-term memory processes as an essential part of thought mechanisms, it may be
      possible to gain better understanding into spontaneous thought phenomena that
      have remained unaccounted for until now.

PMID- 15505973
TI  - Cognitive and behavioral profile in a case of right anterior temporal lobe
      neurodegeneration.
AB  - Semantic dementia (SD) is a clinical variant of frontotemporal lobar degeneration
      (FTLD) characterized by progressive deterioration of semantic memory with
      relative sparing of other cognitive functions. It is associated with mainly left
      anterior temporal atrophy, and is also referred to as "left-temporal lobe
      variant" of FTLD. Recently, patients with mainly right-sided atrophy, or "right
      temporal lobe variant"(RTLV), have been described. While some authors have
      reported that the initial and most significant deficit in these right-sided cases
      is a difficulty in recognizing famous people, others have observed that major
      behavioral abnormalities are the presenting symptoms. Here we report a detailed
      neuropsychological, language, behavioral and neuroimaging assessment of JT, a
      case of right temporal lobe variant of FTLD. JT showed early and prominent
      behavioral changes accompanied by a severe impairment in recognizing foods by
      their look, flavor or name. Later she also developed a difficulty in recognizing
      familiar people and objects. Standardized caregiver questionnaires of JT's pre-
      and post-morbid personality and interpersonal functioning showed that she went
      from being a flexible, dominant, extraverted, person to showing rigid, submissive
      and introverted behaviors. Her levels of neuroticism significantly increased,
      while her scores on agreeableness and cognitive and emotional empathy dropped.
      Voxel-based morphometry (VBM) showed most significant atrophy in the right
      amygdala/anterior hippocampal complex and collateral sulcus, extending to the
      right insula. We discuss the atypical cognitive and behavioral features of this
      case of RTLV of FTLD and stress the importance of behavioral changes and atypical
      semantic deficits for early diagnosis.

PMID- 15505974
TI  - The (neuropsychological) exploration of space.

PMID- 15505975
TI  - Visual and tactile length matching in spatial neglect.
AB  - Previous studies have shown that many patients with spatial neglect underestimate
      the horizontal extent of leftwardly located shapes (presented on screen or on
      paper) relative to rightwardly located shapes. This has been used to help explain
      their leftward biases in line bisection. In the present study we have tested
      patients with right hemisphere damage, either with or without neglect, on a
      comparable length matching task, but using 3-dimensional objects. The task was
      executed first visually without tactile contact, and second through touch without
      vision. In both sense modalities, we found that patients with neglect, but not
      those without, tended to underestimate leftward located objects relative to
      rightward located objects, differing significantly in this regard from healthy
      subjects. However these lateral biases were not as frequent or as pronounced as
      in previous studies using 2-D visual shapes. Despite the similar asymmetries in
      the two sense modalities, we found only a small correlation between them, and
      clear double dissociations were observed among our patients. We conclude that
      leftward length underestimation cannot be attributed to any one single cause.
      First it cannot be entirely due to impairments in the visual pathways, such as
      hemianopia and/or processing biases, since the disorder is also seen in the
      tactile modality. At the same time, however, length underestimation phenomena
      cannot be fully explained as a disruption of a supramodal central size processor,
      since they can occur in either vision or touch alone. Our data would fit best
      with a multiple-factor model in which some patients show leftward length
      underestimation for modality-specific reasons, while others do so due to a more
      high-level disruption of size judgements.

PMID- 15505976
TI  - Comparison of the Milner and Bisiach Landmark Tasks: can neglect patients be
      classified consistently?
AB  - The aim of the presented studies was to investigate whether classifications of
      neglect patients into perceptual (i.e. identifying a patient as suffering from
      mainly attentional/space representation deficits) and premotor (judging the main
      impairment to be related towards actions into contralesional space) categories
      are consistent across similar Landmark techniques that have, in the past, been
      designed to tease these potentially overlapping aspects of hemispatial neglect
      apart. Thirteen patients with hemispatial neglect were tested both with the
      Landmark Test, adapted from Milner et al. (1992; 1993) in which they had to
      manually point to the half of a centrally pre-bisected line that, to them,
      appeared shorter and the motor version of the Bisiach Landmark Test (Bisiach et
      al., 1998) in which, rather than just judging a centrally prebisected line, they
      had to judge asymmetrically bisected lines as well. The specific question was
      whether these two tasks, which are very similar, would categorise the same set of
      patients in the same way. Most patients could be classified into either the
      premotor or perceptual category in each task, but no consistent categorisation
      emerged across the two tests. Just three out of the thirteen patients were
      consistently classified across both tests. Despite the apparent similarity of the
      two tests the Milner Landmark Test proved to be much more sensitive to
      identifying even a slight perceptual bias and seems therefore the test of choice
      if identification of perceptual bias is the major interest.

PMID- 15505977
TI  - Impaired spatial working memory: one component of the visual neglect syndrome?
AB  - Both impaired spatial working memory (SWM) and unilateral neglect may follow
      damage to the right parietal lobe. We propose that impaired SWM can exacerbate
      visual neglect, due to failures in remembering locations that have already been
      searched. When combined with an attentional bias to the ipsilesional right side,
      such a SWM impairment should induce recursive search of ipsilesional locations.
      Here we studied a left neglect patient with a right temporoparietal haemorrhage.
      On a nonlateralised, purely vertical SWM task, he was impaired in retaining
      spatial locations. In a visual search task, his eye position was monitored while
      his spatial memory was probed. He recursively searched through right stimuli, re
      fixating previously inspected items, and critically treated them as if they were
      new discoveries, consistent with the SWM deficit. When his recovery was tracked
      over several months, his SWM deficit and left neglect showed concurrent
      improvements. We argue that impaired SWM may be one important component of the
      visual neglect syndrome.

PMID- 15505978
TI  - Spatial representations and multiple-visual-systems hypotheses: evidence from a
      developmental deficit in visual location and orientation processing.
AB  - AH, a young, well-educated woman, has a developmental deficit in processing
      visual location and orientation information. Her deficit manifests itself in a
      wide range of visual tasks, including visually-guided reaching, copying pictures
      and words, and responding verbally to the location or orientation of visual
      stimuli; however, her performance in non-visual localization tasks is intact.
      AH's visual location and orientation errors are systematic left-right or up-down
      reflections (e.g., reaching to the far right for an object on the far left). More
      specifically, the errors involve reflection across the point where AH's attention
      is focused, regardless of where her eyes are fixated. These results imply that at
      some level(s) of the visual system, locations and orientations of visual stimuli
      are represented in a spatial coordinate system with an origin defined by the
      focus of attention. In these attention-centered representations location is
      specified in terms of distance and direction of displacement from the attentional
      focus along horizontal and vertical reference axes. AH's errors, I argue, result
      from misrepresentation of displacement direction (e.g., left rather than right,
      down rather than up) along a reference axis. Several visual variables
      dramatically affected AH's performance in visual location and orientation tasks:
      She was much more accurate for stimuli that were brief, moving, flickering, low
      in contrast, or high in eccentricity, than for those that were long in duration,
      stationary, continuous, high in contrast, and low in eccentricity. These results
      suggest that location and orientation are computed in each of two visual
      subsystems, which I call transient and sustained, and that AH's deficit affects
      only the sustained subsystem. I argue that AH's performance poses challenges to
      multiple-visual-subsystems hypotheses proposed by Ungerleider and Mishkin (1982)
      and by Milner and Goodale (1995).

PMID- 15505979
TI  - Grasping what is graspable: evidence from visual form agnosia.
AB  - Patient DF has profound visual form agnosia. Despite this, she has no problem
      adjusting her finger-thumb grip aperture to the width of objects when reaching to
      grasp them. In a previous study, however, she was found to have great difficulty
      in scaling her grip aperture when attempting to grasp a transparent disc through
      two holes cut into it. This problem was attributed to a putative difference
      between the visual processing of size and distance in the brain, whereby DF
      retained the capacity for processing object size but not the separation between
      distinct elements such as holes. In the present study we have tested this idea
      more directly, and found no evidence to support such a distinction. Nonetheless,
      we replicated our earlier finding that DF is unable to produce normal prehension
      movements when attempting to grasp transparent stimuli by placing her digits into
      holes. We suggest that, whilst some simple objects offer themselves directly to
      the dorsal stream for grasping, an intact ventral stream is required to respond
      appropriately to more complex stimuli.

PMID- 15505980
TI  - Prism adaptation and spatial attention: a study of visual search in normals and
      patients with unilateral neglect.
AB  - Visuomotor adaptation to a prism-induced lateral displacement of the visual field
      induces mild perceptual biases in healthy individuals and improves symptoms of
      unilateral neglect. The present study employed a speeded visual search task to
      test the hypothesis that prism adaptation induces an adaptive redistribution of
      selective spatial attention. In Experiment 1, 32 neurologically healthy, right
      handed participants were adapted to a 150 prism-induced lateral (left or right)
      displacement of the visual field. Spatial attention was measured by search time
      and error-rate in unique-feature ("preattentive") and feature-absent ("serial")
      visual search tasks, before and after prism adaptation. The single target
      appeared at different locations within arrays of 12, 24 or 48 items. Contrary to
      the attentional hypothesis, the pattern of search performance across the display
      remained unchanged following prism adaptation. In Experiment 2, we tested four
      patients with unilateral right hemisphere damage on the visual search tasks,
      before and after adaptation to 15 degrees rightward-displacing prisms. All four
      patients showed a pathological gradient of spatial attention toward the
      ipsilesional side prior to adaptation. Consistent with the results from
      Experiment 1, the gradient in search performance shown by the patients did not
      change following prism adaptation. Taken together, these findings suggest that
      the perceptual aftereffects in normals and amelioration of unilateral neglect
      following prism adaptation are not mediated by an adaptive redistribution of
      spatial attention.

PMID- 15505981
TI  - 2D but not 3D: pictorial-depth deficits in a case of visual agnosia.
AB  - Patients with visual agnosia exhibit acquired impairments in visual object
      recognition, that may or may not involve deficits in low-level perceptual
      abilities. Here we report a case (patient DM) who after head injury presented
      with object-recognition deficits. He still appears able to extract 2D information
      from the visual world in a relatively intact manner; but his ability to extract
      pictorial information about 3D object-structure is greatly compromised. His
      copying of line drawings is relatively good, and he is accurate and shows
      apparently normal mental rotation when matching or judging objects tilted in the
      picture-plane. But he performs poorly on a variety of tasks requiring 3D
      representations to be derived from 2D stimuli, including: performing mental
      rotation in depth, rather than in the picture-plane; judging the relative depth
      of two regions depicted in line-drawings of objects; and deciding whether a line
      drawing represents an object that is 'impossible' in 3D. Interestingly, DM failed
      to show several visual illusions experienced by normals (Muller-Lyer and Ponzo),
      that some authors have attributed to pictorial depth cues. Taken together, these
      findings indicate a deficit in achieving 3D intepretations of objects from 2D
      pictorial cues, that may contribute to object-recognition problems in agnosia.

PMID- 15505982
TI  - A quantitative assessment of depression and thyroid dysfunction secondary to
      interferon-alpha therapy in patients with hepatitis C.
AB  - The most effective treatment for hepatitis C virus (HCV) is interferon-alpha
      (IFN) therapy in combination with ribavirin. Although symptoms of depression are
      among the most common side effects of IFN therapy in treating patients with HCV,
      the mechanisms by which IFN produces these neuropsychiatric side effects remain
      unclear. In the brain, IFNs are involved in a number of regulatory functions,
      including but not limited to regulation of the endocrine system via the
      hypothalamic-pituitary-adrenal and -thyroid axes. The purpose of this study was
      to assess the effect of IFN therapy on thyroid function and to characterize the
      relationship between thyroid dysfunction and major depressive disorder during IFN
      therapy in patients with hepatitis C. Thirty-three patients with HCV were
      administered the Structured Clinical Interview for Diagnostic and Statistical
      Manual of Mental Disorders (DSM-IV) Axis I Disorders (SCID) and completed the
      Beck Depression Inventory (BDI). Patients were on IFN for an average of 6 to 12
      months depending on their viral genotype. Serum samples were collected at
      baseline, during and after IFN therapy, and measured for free thryoxine (FT4) and
      TSH levels. Patients who developed IFN-induced depression were treated with
      selective serotonin reuptake inhibitor antidepressants. Only one patient
      developed transient IFN-induced overt hypothyroidism, but he did not develop
      depression. Analysis of variance showed that there were no significant
      differences in either FT4 or TSH serum levels between patients who developed
      major depressive disorder (MDD) (no.= 10) during IFN therapy and those who did
      not (no.=23). These results illustrate the frequency and severity of depressive
      symptoms associated with IFN therapy and the apparent absence of a relationship
      between IFN-induced MDD and changes in thyroid function.

PMID- 15505983
TI  - Assessment of adrenocortical function and autoantibodies in a baby born to a
      mother with autoimmune polyglandular syndrome Type 2.
AB  - We describe the case of a baby born to a mother with Addison's disease in the
      context of Autoimmune Polyendocrine Syndrome Type 2. Adrenal cortex
      autoantibodies and steroid 21-hydroxylase autoantibodies were detectable in the
      sera of both mother and baby, suggesting the transplacental passage of these
      autoantibodies. Adrenal autoantibodies were present in the baby's serum at
      delivery, at 3, 6 and till 34 months of age but no signs of clinical or
      subclinical adrenal insufficiency were found in the baby during the observation
      period. These data suggest that the presence of adrenal autoantibodies in serum
      alone is not a sufficient cause for the development of autoimmune adrenalitis.

PMID- 15505984
TI  - Differentiation of cultured mice bone marrow into osteoblast-like cells results
      in acquisition of sex-specific responsiveness to gonadal steroids.
AB  - We have previously demonstrated that mouse skeletal tissue, rat bone as well as
      rat or human derived bone cells in culture, show a sex-specific response to
      gonadal steroids in stimulation of the specific activity of the BB isozyme of
      creatine kinase (CK). This response could be modified by manipulation of the
      endocrine environment during early postnatal development. Moreover, pretreatment
      with vitamin D up-regulated the sex-specific responsiveness and sensitivity to
      gonadal steroids. In the present study we examine the differentiation pattern
      into osteoblast-like cells using dexamethasone (DEX) and 1,25 dihydroxy vitamin
      D3 (1,25D) and their effect on the acquisition of responsiveness to gonadal
      steroids by the differentiated cells. Cultured femoral bone marrow in the
      presence of DEX or 1,25D or both, were examined for their response to gonadal
      steroids by measuring the specific activities of alkaline phosphatase (AP) and CK
      BB. The constitutive level of CK in both male- and female-derived bone cells was
      decreased by DEX, by 1,25D or by both, whereas the constitutive level of AP was
      increased by DEX while decreased by 1,25D or by both. Following incubation of the
      bone marrow cultures with DEX, treatment with estradiol 17beta (E2, 30 nM, 24 h)
      stimulated CK activity in female derived bone cells, with no effect of treatment
      with dihydrotestosterone (DHT, 300 nM). In contrast, in male derived bone cells,
      DHT but not E2 increased CK activity. This sex-specific response was also
      achieved upon culturing with 1,25D and was significantly augmented by culturing
      with both. No response to gonadal steroids was seen with undifferentiated bone
      marrow cells. All cultures responded to IGF-I when cultured with or without DEX
      and/or 1,25D but with no augmentation by 1,25D. Gonadal steroids increased AP to
      a much lesser extent; but enzyme activity decreased in the presence of 1,25D. IGF
      I stimulated AP slightly with no effect of 1,25D. These findings suggest that
      manipulation of the hormonal milieu in early stages of differentiation sequence
      of osteoblast-like cells, determines the subsequent selective responsiveness of
      the developing bone tissue to gonadal steroids.

PMID- 15505985
TI  - Prior gestational hyperglycemia: a long-term predictor of the metabolic syndrome.
AB  - Little is known about the association between prior gestational hyperglycemia of
      different severity and the subsequent risk for the metabolic syndrome. Eighty-one
      women with prior gestational diabetes mellitus (GDM), 25 with one abnormal value
      at the oral glucose tolerance test (OGTT), and 65 with normal OGTT were studied
      after a mean of 8.5 yr from the index pregnancy. Patients with prior gestational
      hyperglycemia (both one abnormal value at the OGTT and GDM) showed a worse
      metabolic pattern than subjects with gestational normoglycemia [respectively
      higher values of body mass index (BMI), waist, blood pressure, serum glucose,
      insulin, C-peptide, homeostatic model assessment (HOMA), fibrinogen and lower
      levels of HDL-cholesterol]. Prevalence of the metabolic syndrome and its
      components was 2-4-fold higher in women with prior gestational hyperglycemia (and
      10-fold higher if pre-pregnancy obesity coexisted) when compared to normoglycemic
      controls; in a Cox proportional hazard model, after adjustments for age and pre
      pregnancy BMI, gestational hyperglycemia and pre-pregnancy BMI predicted
      subsequent metabolic syndrome [respectively: hazard ratio (HR)=4.26 and HR=1.21]
      and most of its components. In the same model, the highest quartile of fasting
      serum glucose at the OGTT of the index pregnancy was significantly associated to
      the metabolic syndrome and its components. Gestational hyperglycemia and fasting
      glucose values were also associated to subsequent fibrinogen values, but not to
      albumin excretion rates. In young adult women, prior gestational hyperglycemia
      (particularly abnormal fasting glucose values), above all in combination with pre
      pregnancy obesity, anticipates a subsequent syndrome at high cardiovascular risk
      and, possibly, a mild chronic inflammatory response.

PMID- 15505986
TI  - Failure to use measurement of megalin secretory components complexed with serum
      thyroglobulin as a tool to identify metastases after surgery in papillary thyroid
      cancer.
AB  - When thyroid follicles are intact, some colloidal thyroglobulin (Tg) reaches the
      circulation by megalin-mediated transcytosis and is to various extents complexed
      with megalin secretory components. In contrast, in papillary thyroid cancer
      (PTC), serum Tg is not complexed with megalin because it is directly secreted by
      tumor cells. Here we attempted to use measurement of megalin secretory components
      to distinguish PTC patients with thyroid remnant plus metastases from those with
      thyroid remnant only, after thyroidectomy and before 131I ablation. Tg values in
      anti-Tg antibodies (TgAb)-free sera from 5 PTC patients with thyroid remnant plus
      metastases and 12 PTC patients with thyroid remnant only were measured following
      pre-adsorption with uncoupled protein A beads or with protein A beads coupled
      with antimegalin antibodies. The degree of Tg pre-adsorption with antimegalin
      antibodies was minimal, with no substantial differences between the two groups.
      Thus, we concluded that measurement of megalin secretory components is unlikely
      to be useful to identify the origin of serum Tg in PTC patients after
      thyroidectomy.

PMID- 15505987
TI  - Serum prostate-specific antigen concentration is increased in acromegalic women.
AB  - Prostate-specific antigen (PSA) is a serine proteases produced by prostatic
      epithelial cells detectable in male serum and seminal plasma. PSA is also
      expressed in some female tissues and fluids and is increased in hirsute women
      showing a positive correlation with androgens. Accordingly, it has been suggested
      that PSA might be a marker of androgen action in women. The aim of this
      observational study was to assess serum PSA concentration in acro megalic women
      with active disease, in remission or during somatostatin analogs therapy. Forty
      four acromegalic women, 15 with active disease, 10 in remission and 19 under long
      acting somatostatin analogs therapy were enrolled in the study; 273 normal women
      matched for age, body mass index, with no signs of hirsutism, served as controls.
      Serum PSA, 3a-androstanediol (3alpha-AG), total testosterone (T), DHEAS, LH, FSH
      and estradiol were assessed. No patient or control had been given estrogen or
      antiandrogen drugs; no acromegalic women had hyperprolactinemia or
      hypopituitarism. Serum PSA concentration was significantly higher in acromegalic
      patients than in control subjects (p < 0.0001). Patients with active acromegaly
      or under somatostatin analogs therapy had significant higher serum PSA
      concentration than controls, while patients in remission after adenomectomy did
      not differ. Serum PSA was detectable in serum of 75% acromegalic women and 45% of
      controls. In addition 24% of acromegalic women had serum PSA concentrations
      higher than the mean +/- 2SD of control subjects. Differences in serum PSA levels
      did not reach statistical significance in the different acromegalic subgroups
      possibly because of the small number of subjects, but patients with active
      acromegaly had higher serum PSA levels than patients under somatostatin analogs
      therapy or in remission. Acromegalic women had significantly higher serum PSA
      concentrations than controls both before and after menopause (p < 0.01). 3alpha
      AG (p < 0.05) and T (p < 0.01) were higher in acromegalic than in control
      subjects in pre-menopause (PM) but not in post-menopause (M). A correlation was
      found in the whole group of acromegalic patients between serum PSA and 3a-AG
      concentrations (r = 0.3, p < 0.01). In conclusion, acromegalic is associated with
      an increase in serum PSA concentrations as a group, although this increase is
      observed, at an individual level, in only 24% of cases. Patients whose disease is
      controlled by somatostatin analogs or has been cured by pituitary adenomectomy
      tend to have lower serum PSA levels than patients with active disease. M patients
      tend to have lower PSA values than PM women, consistent with the main androgen
      control of PSA production. However, the observation that M women still have
      higher serum PSA levels than controls suggest that in acromegaly PSA is regulated
      not only by androgens but also by the GH/IGF-I system itself.

PMID- 15505988
TI  - Anthropometric, hormonal and biochemical differences in lean and obese women
      before and after menopause.
AB  - The menopausal status is associated with an increased risk of metabolic and
      cardiovascular diseases. Since the post-menopausal modifications have not been
      clearly investigated in obese women, we evaluated the influences of menopausal
      status on anthropometric, hormonal and biochemical characteristics in selected
      groups of normal-weight and obese women. We studied 92 female outpatients: 24
      normal-weight pre-menopausal (Pre-NW) [body mass index (BMI) 23.6 +/- 0.48, age
      44.8 +/- 0.68], 24 normal-weight post-menopausal (Post-NW) (BMI 23.7 +/- 0.44,
      age 55.5 +/- 0.69), 24 obese pre-menopausal (pre-OB) (BMI 32.3 +/- 0.45, age 44.6
      +/- 0.75), 20 obese post-menopausal women (Post-OB) (BMI 32.9 +/- 0.57, age 55.2
      +/- 0.82). All the subjects were non smokers and free from hypertension, diabetes
      or impaired glucose tolerance (IGT). Anthropometric parameters, body composition,
      17 beta-estradiol, LH, FSH, androstenedione, SHBG, testosterone and leptin were
      determined. Free androgen index (FAI) and insulin resistance index (HOMA) were
      calculated. In comparison with Pre-OB, Post-OB had higher values of waist
      circumferences (p < 0.02), while Post-NW showed no difference. Total and LDL
      cholesterol were high in Post-NW women, whereas in the obese subjects they were
      already elevated in the premenopausal period. SHBG levels declined and FAI
      increased in Post-OB in comparison with Pre-OB. SHBG levels showed an inverse
      correlation with BMI, waist and waist-to-hip ratio (WHR), while FAI positively
      correlated with waist values. Serum leptin levels were higher in Post-OB than in
      Pre-OB, whereas they were similar in normal-weight women. The rise of leptin
      levels may be related to the greater abdominal fat deposition. In addition,
      menopausal status of uncomplicated obese women is associated with a greater
      abdominal fat deposition and with higher values of free androgen index, which may
      be considered as factors of cardiovascular risk.

PMID- 15505989
TI  - Bilateral adrenalectomy for Cushing's syndrome: a comparison between laparoscopy
      and open surgery.
AB  - We report our experience with bilateral adrenalectomy for treatment of Cushing's
      syndrome and we compare the outcome of laparoscopy with open surgery in terms of
      effectiveness and safety. A series of 23 patients underwent bilateral
      adrenalectomy for treatment of Cushing's syndrome [Cushing's disease in 16,
      ectopic ACTH syndrome in 2, and ACTH-independent macronodular adrenal hyperplasia
      (AIMAH) in 5 cases]. From 1993 to 1996, all patients were treated using an open
      approach (Group A), while from 1997 all patients were treated using a
      transperitoneal laparoscopic approach (Group B). The comparison between the 2
      groups was performed considering patients characteristics, operative times, blood
      losses, intraoperative and post-operative complications, analgesic consumption,
      post-operative hospital stay and recovery. Open surgery was performed in 10
      patients and laparoscopy in 13 patients. No significant difference was recorded
      between the two groups as to patients' characteristics and complications. Mean
      operative time was significantly increased in Group B, while post-operative
      hospital stay was significantly longer in Group A. Laparoscopic bilateral
      adrenalectomy can be safely and effectively employed to treat Cushing's syndrome.
      However, long operatives times may represent a limitation especially in high risk
      patients.

PMID- 15505990
TI  - There are no acute cardiac effects of a single iv dose of human ghrelin in severe
      growth hormone deficient patients.
AB  - It has previously been suggested that ghrelin mediates GH-independent biologic
      activities on the heart. We investigated the acute effects on cardiac contraction
      of a single iv administration of human ghrelin (in a dose of 1 microg/kg) in
      severe untreated GH deficient subjects. Prior to the ghrelin infusion, an
      echocardiographic examination was performed at rest (baseline), after physiologic
      saline and during dobutamine stress echocardiography (DSE) to exclude a
      preexisting (subclinical) myocardial dysfunction. To evaluate the acute cardiac
      effect of infusion and during DSE the velocity of left ventricular (LV) wall
      contraction was measured continuously by echocardiography. Despite severe GH
      deficiency we observed in all subjects a normal cardiac function at rest after
      physiologic saline and during DSE. No acute changes in cardiac performance or
      cardiac parameters could be observed after a single iv dose of ghrelin. Also, no
      important increase in GH secretion was detected after ghrelin administration. Our
      study suggests that, in contrast to hexarelin, a single iv administration of
      ghrelin in a physiological dose has no acute effects on cardiac function in
      severe GH deficiency. This suggests that GH-independent effects of ghrelin play
      no important role in the acute regulation of cardiac function in man.

PMID- 15505991
TI  - Erectile dysfunction associates with endothelial dysfunction and raised
      proinflammatory cytokine levels in obese men.
AB  - Erectile and endothelial dysfunction may have some shared pathways through a
      defect in nitric oxide activity. We evaluated associations between erectile
      function, endothelial function and markers of systemic vascular inflammation in
      80 obese men, aged 35-55 yr, divided into two equal groups according to the
      presence/absence of erectile dysfunction. Compared with non-obese age-matched men
      [no.=50, body mass index (BMI)=24 +/- 1], obese men (all) had impaired indices of
      endothelial function as suggested by the reduced mean blood pressure and platelet
      aggregation responses to L-arginine, and higher circulating concentrations of the
      proinflammatory cytokines interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin
      18 (IL-18), as well as C-reactive protein (CRP). The mean erectile function score
      was 14 +/- 4 (range 7-19) in obese men with erectile dysfunction and 23.5 +/- 1
      (range 22-25) in obese men without erectile dysfunction. Endothelial function
      showed a greater impairment in impotent obese men as compared with potent obese
      men. The mean blood pressure and platelet aggregation decreases following L
      arginine were -1.5 +/- 1.1 mmHg and -1.1 +/- 1.2%, respectively, in obese men
      with erectile dysfunction, and -3.4 +/- 1.2 mmHg and -5.6 +/- 2.1%, respectively,
      in obese men without erectile dysfunction (p < 0.01). Circulating CRP levels were
      significantly higher in obese men with erectile dysfunction as compared with
      obese men without erectile dysfunction (p < 0.05). Erectile function score was
      positively associated with mean blood pressure responses to L-arginine and
      negatively associated with BMI, waist-to-hip ratio (WHR), and CRR Erectile and
      endothelial dysfunction associate in obese men and may contribute to their raised
      cardiovascular risk through impaired nitric oxide availability elicited by a low
      grade inflammatory state.

PMID- 15505992
TI  - Differential regulation of gonadotropins and glycoprotein hormone alpha-subunit
      by IGF-I in anterior pituitary cells from male rats.
AB  - IGF-I has been demonstrated to stimulate basal and GnRH-induced gonadotropin
      release. IGF-I also elicites alpha-subunit secretion in human pituitary tumor
      cells. The aims of this study were to evaluate both the effect of IGF-I on
      gonadotropin LH-beta and FSH-beta mRNA levels and glycoprotein alpha-subunit gene
      expression in cultured rat anterior pituitary cells. The exposure of pituitary
      cells to recombinant human IGF-I (rhlGF-I; 2 microg/ml) for 72 h markedly
      stimulated basal LH and FSH release whereas their mRNA levels remained
      unmodified. IGF-I elicited a-subunit release from pituitary cells (p < 0.01) and
      augmented its mRNA levels. Exposure to IGF-I consistently reduced GH release from
      pituitary cells. This study shows that the gonadotropin-releasing effects of IGF
      I are not paralleled by changes in their mRNAs whereas IGF-I stimulates not only
      alpha-subunit release but also its mRNA levels. This study provides the first
      observation of alpha-subunit regulation by IGF-I in normal pituitary cells, where
      a differential regulation between release and synthesis for gonadotropin a-and 1
      subunits is also shown.

PMID- 15505993
TI  - Seasonal variation of serum 25 hydroxy D3 in residents of Tehran.
AB  - BACKGROUND AND AIM: vitamin D is essential for bone health. It has been shown
      that in many communities serum levels of vitamin D can be subject to seasonal
      variations but so far no study has been conducted on this variable in natives of
      Tehran. SUBJECTS AND METHODS: 1172 natives of Tehran, 682 women and 490 men, aged
      3-69 yr entered the study. Sampling was performed monthly except during Ramadhan,
      the holy month of Islamic fasting. Serum 25-hydroxyvitamin D (25-OHD) was
      measured using protein binding assay and levels below 20 ng/ml were determined as
      vitamin D deficient. RESULTS: serum 25-OHD concentrations showed monthly
      variations in both sexes but the magnitude of variations was more pronounced in
      men. The nadir of serum levels in both sexes were seen in December and February,
      12 +/- 13 and 14 +/- 14 ng/ml in women, and 28 +/- 16 and 24 +/- 18 mg/ml in men,
      respectively with the highest values being seen in October; 29 +/- 29 ng/ml in
      women and 55 +/- 27 ng/ml in men. During the whole period of study the maximum
      values for women were either equal or less than the minimum values for men. The
      values for men during summer and winter (31 +/- 17 and 28 +/- 22 ng/ ml,
      respectively) were significantly lower than the values for spring and fall (38 +/
      27 and 43 +/- 29 ng/ml respectively). In women there was no significant
      difference in the values of the first three seasons and only the values
      pertaining to winter were significantly different from the values of fall.
      CONCLUSIONS: the absence of expected seasonal variations in women coupled with
      obvious deficiency of vitamin D can be attributed to patterns of life style and
      also to the traditional clothing of the women of Tehran. Nationwide strategies to
      improve the vitamin D status of the community, specially for women and children,
      are highly recommended.

PMID- 15505994
TI  - Pamidronate treatment in acute vitamin D intoxication.
AB  - Management with glucocorticoid, high iv fluid saline intake, furosemide and
      calcitonin may not result in a favorable reduction of hypercalcemia and may cause
      several side effects in infants with acute vitamin D intoxication. The
      bisphosphonate pamidronate, a specific inhibitor of bone resorption through
      osteoclast mediation was successfully used in a 6-month old infant with acute
      vitamin D intoxication managed in the Pediatric Emergency and Intensive Care
      Unit, after an ineffective trial of hydration, furosemide, calcitonin and
      prednisolone. After a double infusion of pamidronate on two consecutive days (1
      mg/kg/day), an early and safe correction of hypercalcemia/hypercalciuria was
      supplied. Pamidronate therapy may be considered in patients with hypercalcemia
      secondary to acute vitamin D poisoning.

PMID- 15505996
TI  - Spontaneous short-term remission of primary hyperparathyroidism from infarction
      of a parathyroid adenoma.
AB  - We report a 39-yr-old woman with spontaneous short-term remission of primary
      hyperparathyroidism (PHPT). She was referred to our Department for PHPT with
      bilateral kidney stones diagnosed elsewhere; at the time of our observation she
      had developed anterior neck pain associated with swelling and tenderness.
      Biochemical data (serum ionized calcium and PTH) suggested a remission of the
      PHPT. The local symptoms gradually improved and disappeared over the next several
      days without therapy. Serum ionized calcium and PTH levels remained normal for up
      to 11 months. Subsequently, the patient had a recurrence of PHPT with mild
      hypercalcemia and elevated PTH levels. The patient underwent surgery and
      pathological examination revealing a 1.0 x 1.2 cm parathyroid adenoma with areas
      of necrosis with hemosiderinladen macrophages. In conclusion, we describe a case
      of spontaneous short-term remission of PHPT due to infarction of parathyroid
      adenoma.

PMID- 15505995
TI  - Cortisol, depression and reduced cortico-cortical cross-talk in Cushing's
      syndrome.
AB  - In the present report assumed relationships between hypercortisolism, depression
      and cortico-cortical cross-talk in Cushing's syndrome were investigated.
      Electroencephalographic (EEG) recordings and depression ratings from three
      patients diagnosed with mild, moderate and severe hypercortisolism were obtained.
      Reductions in cortico-cortical cross-talk as quantified by EEG coherence together
      with increases in depression were observed in the moderate and severe as compared
      to the mild hypercorticolism state. These findings provide preliminary evidence
      for the hypothesis that loss of cortico-cortical cross-talk might be linked to
      hypercortisolism and the severity of depressive symptoms.

PMID- 15505997
TI  - Epinephrine producing pheochromocytoma. Is the secretory pattern decisive for the
      clinical manifestation?
AB  - Adrenal incidentalomas are becoming a major clinical problem, due to increasingly
      frequent radiological examinations. We present two cases of patients referred to
      our department with a finding of an unsuspected adrenal mass. Both of them were
      normotensive and without symptomatology typical for pheochromocytoma. In one
      patient we found 20-times higher levels of epinephrine and 3-times higher levels
      of dopamine in 24-h urine, in the second patient there were 8-times higher levels
      of epinephrine alone. Norepinephrine in urine, as well as values of all adrenal
      cortical hormones were normal. The diagnosis of pheochromocytoma was confirmed in
      both cases by a 123I-metaiodobenzylguanidine (MIBG) scintigraphy. The patients
      underwent adrenalectomy, which was performed without complications. We conclude
      that levels of single catecholamines excreted are decisive for the clinical
      presentation of pheochromocytoma. Epinephrine producing pheochromocytoma is more
      often oligo- or asymptomatic. We stress the importance of a complete hormonal
      screening in every case of adrenal incidentaloma, with measuring levels of
      catecholamines and/or metanephrines.

PMID- 15505999
TI  - New 2005 patient safety goals are here: don't delay in developing strategies.

PMID- 15505998
TI  - CD38 autoimmunity: recent advances and relevance to human diabetes.
AB  - Human CD38 is a protein which catalyzes the synthesis of nicotinic acid adenine
      dinucleotide (NAADP+) and the conversion of NAD+ to cADPR. Both cADPR and NAADP+
      are powerful intracellular Ca2+ ([Ca2+]i) mobilizers in different cell types.
      Recently, the presence of CD38 autoantibodies has been found in a significant
      number (9-15%) of patients with Type 2 or long-standing Type 1 diabetes. These
      autoantibodies are biologically active, the majority of them (-60%) displaying
      agonistic properties, i.e., [Ca2+]i mobilization in lymphocytic cell lines and in
      pancreatic islets. In cultured rat pancreatic islets, the human autoantibodies
      inhibit glucose-induced insulin release, whereas, in human pancreatic islets CD38
      autoantibodies stimulate glucose-mediated insulin secretion. The clinical
      phenotype of anti-CD38-positive Type 2 diabetes differs from the LADA (latent
      autoimmune diabetes of adults) phenotype. When accurately matched for age and
      obesity, only LADA patients with anti-GAD antibodies, but not GAD-negative/ CD38
      positive patients, have reduced in vivo beta-cell function in comparison to
      antibody-negative patients. Transgenic mice overexpressing CD38 show enhanced
      glucose-induced insulin release, whereas, conversely, CD38 knockout mice display
      a severe impairment in beta-cell function. Few Japanese diabetic patients carry a
      missense mutation in the CD38 gene; in Caucasian patients mutations in the CD38
      gene have not been found. Collectively, these findings suggest that activation of
      CD38 represents an alternative signaling pathway for glucose-induced insulin
      secretion in human beta-cells. More information, however, is necessary to gauge
      the role of CD38 autoimmunity in the context of the natural history of human Type
      1 or Type 2 diabetes.

PMID- 15506000
TI  - Why did 2005 safety goals omit bar coding?

PMID- 15506001
TI  - Bill would increase CMS' authority over JCAHO.

PMID- 15506002
TI  - How to create and monitor your measures of success.

PMID- 15506003
TI  - Clinic serves as a model for care of the uninsured.

PMID- 15506004
TI  - Uninsured cases increase in number, complexity.

PMID- 15506005
TI  - JCAHO surveyors focus on life safety code compliance.

PMID- 15506006
TI  - Manage organizational fear to improve safety.

PMID- 15506007
TI  - Patient safety alert. 'Safety culture' approach guides health system's efforts.

PMID- 15506008
TI  - Feasibility to the sixth power.

PMID- 15506009
TI  - And still more new codes.
AB  - Before reporting the new Category III CPT codes, contact payors to determine both
      acceptance of these temporary codes and reimbursement allowances. Documentation
      must clearly support all services performed, and the requirements for an online
      medical evaluation should be followed, with the encounter recorded in the
      individual patient medical record. Hospitals should also review the quarterly
      changes to OPPS codes and descriptors and ensure that Charge Description Masters
      are updated as new codes become effective.

PMID- 15506010
TI  - Shelf price agreements: a novel approach to competitive bidding for arrhythmia
      therapy devices.
AB  - Over the past decade, the financial pressures from variations in reimbursement
      and payer mix, combined with rapidly evolving technology, has forced healthcare
      institutions in the United States to seek out further options for cost savings.
      In the arena of interventional cardiology, the ability to successfully negotiate
      the lowest possible cost for a relatively small number of high-cost devices can
      result in significant savings. Historically, competitive bidding with market
      share guarantee to a preferred vendor or two initially resulted in moderate cost
      savings. However, in 2003 our institution embarked on a novel approach in which
      we defined the price to be paid, and we challenged our vendors to meet that
      price. Early results of this aggressive strategy suggest that it is a successful
      technique in reducing supply costs and maintaining collaborative relationships
      with vendors while remaining fair and competitive.

PMID- 15506011
TI  - Campaign sounds call to action to reduce delay and increase survival for heart
      attacks.

PMID- 15506013
TI  - Sebacinales: a hitherto overlooked cosm of heterobasidiomycetes with a broad
      mycorrhizal potential.
AB  - Within the basidiomycetes, the vast majority of known mycorrhizal species are
      homobasidiomycetes. It was therefore surprising when molecular and
      ultrastructural studies revealed a broad diversity of mycorrhizal associations
      involving members of the heterobasidiomycetous Sebacinaceae, fungi which, due to
      their inconspicuous basidiomes, have been often overlooked. To investigate the
      phylogenetic position of the Sebacinaceae within the basidiomycetes and to infer
      phylogenetic relationships within the Sebacinaceae, we made molecular
      phylogenetic analyses based on nuclear rDNA. We present a well-resolved phylogeny
      of the main lineages of basidiomycetes which suggests that the Sebacinaceae is
      the most basal group with known mycorrhizal members. Since more basal taxa of
      basidiomycetes consist of predominantly mycoparasitic and phytoparasitic fungi,
      it seems possible that a mycorrhizal life strategy, which was transformed into a
      saprotrophic strategy several times convergently, is an apomorphic character for
      the Hymenomycetidae. Mycorrhizal taxa of Sebacinaceae, including mycobionts of
      ectomycorrhizas, orchid mycorrhizas, ericoid mycorrhizas, and jungermannioid
      mycorrhizas, are distributed over two subgroups. One group contains species with
      macroscopically visible basidiomes, whereas members of the other group probably
      lack basidiomes. Sebacina appears to be polyphyletic; current species concepts in
      Sebacinaceae are questionable. Sebacina vermifera sensu Warcup & Talbot consists
      of a broad complex of species possibly including mycobionts of jungermannioid and
      ericoid mycorrhizas. This wide spectrum of mycorrhizal types in one fungal family
      is unique. Extrapolating from the known rDNA sequences in Sebacinaceae, it is
      evident that there is a cosm of mycorrhizal biodiversity yet to be discovered in
      this group. Taxonomically, we recognise the Sebacinaceae as constituting a new
      order, the Sebacinales.

PMID- 15506012
TI  - High phylogenetic diversity among corticioid homobasidiomycetes.
AB  - Homobasidiomycetes display a variety of fruit body morphologies. Examples include
      gilled mushrooms, coral fungi, polypores and puffballs but also species with
      simple crust-like basidiomata, usually called corticioid fungi. The latter group
      has largely been neglected in recent studies of homobasidiomycete evolution. The
      major goal of the present study was to explore the impact that the addition of a
      wide selection of species with crust-like basidiomata would have on
      homobasidiomycete phylogeny. Two genes, 5.8S and 28S in the nuclear rDNA repeats,
      were sequenced and a data set with 178 taxa analysed using neighbour-joining and
      maximum parsimony methods. Support for clades was evaluated by bootstrap. Basal
      nodes generally received weak support and branching order for major clades
      remained largely unresolved. Twelve major groups were recovered and corticioid
      fungi make up a major or important constituent in most of them. Nine groups are
      strongly supported but support for euagarics and polyporoid clades is poor.
      Phlebioid fungi were in earlier studies merged with the polyporoid clade but are
      here identified as a separate clade. Athelia is allied with ectomycorrhizal
      genera, inter alia Piloderma and Amphinema, in a separate clade forming a sister
      group to the boletes. We conclude that corticioid fungi hold a considerable share
      of the phylogenetic diversity displayed by homobasidiomycetes, and should always
      be considered when phylogenetic studies of larger basidiomycetes are designed.

PMID- 15506014
TI  - Phylogenetic relationships of Plasmopara, Bremia and other genera of downy mildew
      pathogens with pyriform haustoria based on Bayesian analysis of partial LSU rDNA
      sequence data.
AB  - Bayesian and maximum parsimony phylogenetic analyses of 92 collections of the
      genera Basidiophora, Bremia, Paraperonospora, Phytophthora and Plasmopara were
      performed using nuclear large subunit ribosomal DNA sequences containing the D1
      and D2 regions. In the Bayesian tree, two main clades were apparent: one clade
      containing Plasmopara pygmaea s. lat., Pl. sphaerosperma, Basidiophora, Bremia
      and Paraperonospora, and a clade containing all other Plasmopara species.
      Plasmopara is shown to be polyphyletic, and Pl. sphaerosperma is transferred to a
      new genus, Protobremia, for which also the oospore characteristics are described.
      Within the core Plasmopara clade, all collections originating from the same host
      family except from Asteraceae and Geraniaceae formed monophyletic clades;
      however, higher-level phylogenetic relationships lack significant branch support.
      A sister group relationship of Pl. sphaerosperma with Bremia lactucae is highly
      supported. Within Bremia lactucae s. l., three distinct clades are evident, which
      only partly conform to the published host specificity groups. All species of the
      genera Basidiophora, Bremia, Paraperonospora and Plasmopara included in the
      present study were investigated for haustorial morphology, and all had ellipsoid
      to pyriform haustoria, which are regarded as a diagnostic synapomorphy of the
      whole clade. Aspects of coevolution and cospeciation within the downy mildew
      pathogens with ellipsoid to pyriform haustoria are briefly discussed.

PMID- 15506015
TI  - A survey of Daldinia species with large ascospores.
AB  - Specimens of Daldinia (Xylariaceae) from around the world possessing large
      ascospores were studied for teleomorphic and anamorphic morphological characters
      and compared with authentic material of D. grandis. A culture made from a
      specimen of D. grandis collected from Ecuador produced stromatic structures, but
      no conidiogenous structures referable to known xylariaceous anamorphs were
      observed. D. grandis is reconsidered and viewed as a species of warmer climates
      in the Americas. Three new species are recognised from new combinations of
      anamorphic and teleomorphic characters: (1) D. novaezelandiae sp. nov. from New
      Zealand, a fungus obviously related to D. bakeri, which is also reported from
      that country; (2) D. dennisii sp. nov., from Australia and New Zealand, of which
      two varieties are erected; and (3) D. loculatoides sp. nov., from the UK and
      Canada with affinities to D. loculata. The type of Sphaeria durissima was
      identified as D. loculata. Notes on further Daldinia spp. are included.

PMID- 15506016
TI  - Sequestrate Lactarius species from tropical Africa: L. angiocarpus sp. nov. and
      L. dolichocaulis comb. nov.
AB  - Lactarius angiocarpus sp. nov. is described from miombo woodlands in Zambia. It
      is the third sequestrate representative of the Russulaceae described from
      tropical Africa. Morphological characters and DNA sequence data support its
      placement in Lactarius subgen. Plinthogali. Molecular kinship analyses confirm a
      multiple origin of sequestrate Russulaceae spp. As none of the previously
      sequenced sequestrate Russulaceae spp. has been assigned to the Plinthogali
      clade, the placement of L. angiocarpus indicates an additional point of origin of
      derivative sporocarp types within the Russulaceae. Within the same subgenus,
      another tropical African sequestrate species, L. dolichocaulis comb. nov. (syn.
      Arcangeliella dolichocaulis) is recognized.

PMID- 15506017
TI  - Morphological and molecular characterisation of Geosmithia putterillii, G.
      pallida comb. nov. and G. flava sp. nov., associated with subcorticolous insects.
AB  - Geosmithia putterillii is an anamorphic fungus with connections to bark beetles.
      Genetic variability of 89 isolates traditionally grouped in G. putterillii and G.
      lavendula isolated from different geographical regions from subcorticolous
      insects and from other unspecific substrata was assessed using RAPD, sequencing
      of the ITS region (ITS1-5.8SrDNA-ITS2) and morphological characters. RAPD
      analysis revealed eight distinct groups. One group was represented by G.
      lavendula type strain and showed no relations to any other isolate. Five RAPD
      types with similar ITS sequences and phenotype were related to the ex-type strain
      of Penicillium pallidum (generally given as a synonym of G. putterillii). Because
      of unique phylogenetic position and a phenotype markedly different from G.
      putterillii, the new combination G. pallida is made here. For another group of
      isolates formerly identified as G. putterillii the new species G. fiava is
      described based on a characteristic RAPD-type, a unique ITS sequences and a
      different phenotype. These newly recognized species are stable in culture and
      with worldwide distribution.

PMID- 15506018
TI  - Restriction fragment length polymorphism of mitochondrial genome of the
      entomopathogenic fungus Beauveria bassiana reveals high intraspecific variation.
AB  - Beauveria bassiana is an entomopathogenic fungus with a growing potential for
      pest control in different agro-ecosystems worldwide. Such potential brings the
      necessity of developing a strain specific typing system. In a previous study, we
      reported the identification of molecular variants in mitochondrial DNA (mtDNA)
      polymorphism in 15 North American isolates. Results indicated a highly conserved
      mitochondrial genome showing only two mitochondrial genotypes (mitotypes). In
      this study we used whole genomic DNA from 18 isolates of B. bassiana, two
      unidentified Beauveria spp., and one each of B. amorpha, B. cylindrospora and B.
      nivea from more diverse origins. By doing single- and double-restriction enzyme
      digestion of total genomic DNA with EcoRI, and HindIII and then probing with
      BbmtE2, the predominance of mitotypes A and B was observed again, along with
      three newly described mitotypes (C to E). Additionally, by using whole B.
      bassiana mtDNA digested with HpaII as probe, we further demonstrate up to nine
      different mitotypes within B. bassiana. With either of the two probes,
      distinguished between members of the genus Beauveria and from Paecilomyces
      farinosus and Metarhizium anisopliae. Phylogenetic analysis could not however
      distinguish B. amorpha and B. nivea isolates from B. bassiana, suggesting a close
      genetic relation between the three species of the genus. Altogether, these
      results show high variability in mitochondrial genome, which can be useful as a
      reliable tool for the biopesticide industry for both species and isolate specific
      identification.

PMID- 15506019
TI  - Isolated root caps, border cells, and mucilage from host roots stimulate hyphal
      branching of the arbuscular mycorrhizal fungus, Gigaspora gigantea.
AB  - Unlike previous reports that have shown that water soluble and volatile compounds
      from roots or root exudates play an important role in precolonization events
      during arbuscular mycorrhizal (AM) fungus-host root interactions (Becard & Piche
      1989, Giovannetti et al. 1993), the results shown here deal with particulate and
      viscous fractions isolated from host roots. Root caps and a slow sedimenting
      particulate fraction (SSPF) were rapidly isolated and separated from Ri T-DNA
      transformed carrot roots (D. carota) grown in liquid culture. In addition, border
      cells (BC) and mucilage were isolated from aseptically grown corn seedlings (Zea
      mays). Root caps, SSPF (composed mainly of small root cap fragments and some
      BCs), BCs, and mucilage all had an associated AM fungus hyphal branching
      stimulator. Root caps stored for 5 d at 4 degrees C appeared to either synthesize
      or slowly release the branching stimulator. Also, isolated root caps from roots
      grown in the absence of P contained more branch stimulating activity than those
      isolated from roots grown in the presence of P. Although the branching
      stimulation activity in particulate fractions was low compared to that of the
      exudate, the particulate fractions can stick to the root surface at considerable
      distances from the root tip. This may be significant during the infection and
      colonization of host roots at sites far removed from the primary location of
      exudation.

PMID- 15506020
TI  - Ionizing radiation attracts soil fungi.
AB  - During the last 15 years, about 2000 strains of 200 species of 98 genera of fungi
      have been isolated from around the Chernobyl Atomic Energy Station. Many of these
      microfungi are capable of growing into and decomposing 'hot particles'; carbon
      based radioactive graphite from the reactor and there are suggestions that some
      fungi actively direct their growth toward sources of radioactivity, possibly
      attracted to the carbon skeleton of these structures. In our experiments, we
      eliminated the confounding effects of carbon as a fungal resource, by developing
      experimental protocols that expose fungal spores and their germinating hyphae to
      directional sources of ionizing radiation allowing us to measure fungal response
      to ionizing radiation per se. We show that both beta and gamma radiation promote
      directional growth of hyphae towards the source of ionizing radiation.

PMID- 15506021
TI  - From repair to prevention: the wellness model of care.

PMID- 15506022
TI  - Surgical extrusion technique for clinical crown lengthening: report of three
      cases.
AB  - Although a number of techniques have been proposed for clinical crown lengthening
      procedures, all have some limitation in terms of function and esthetics. This
      report presents the clinical and radiographic results of a surgical extrusion
      technique for clinical crown lengthening. Atraumatic surgical extrusion using a
      specially designed instrument (Periotome) was performed in three cases in which
      it was expected that extensive resective osseous surgery would have to be used
      for crown lengthening. Full-thickness mucoperiosteal flaps were raised both
      labially and palatally. The tooth was carefully luxated and extruded to the
      desired position without damaging the marginal bone area or root apex. No rigid
      splint was applied. Clinical examinations performed for more than 1 year after
      surgery revealed probing depths < or = 3 mm around the teeth at all sites,
      without bleeding on probing. The teeth functioned normally, with near-normal
      mobility. Radiographs showed normal periodontal contour consistent with new bone
      formation in the periapical area. Radiographic analysis did not show any evidence
      of root or crestal bone resorption or endodontic problems. The technique
      presented could constitute an alternative surgical approach to performing crown
      lengthening; it does not induce functional or esthetic deformities, especially in
      the anterior region.

PMID- 15506023
TI  - Management and prevention of retrograde peri-implant infection from retained root
      tips: two case reports.
AB  - Fracture of root tips in the maxillary premolar region is not an uncommon finding
      because of the high incidence of bifid and root dilacerations. Therefore, a
      retained root tip may serve as a nidus of infection when a dental implant is
      placed. The likely result is the development of an implant periapical lesion.
      This case report shows the successful management of a rapidly developing implant
      periapical lesion caused by an undetected retained root tip. Initially, systemic
      antibiotics failed to subdue the infection. A retained root fragment was
      retrieved surgically, together with the implant, and a new wide-body implant was
      engaged with DFDBA mixed with tetracycline. A 5-month follow-up showed increased
      radiographic density, and clinical reentry revealed the formation of bone with a
      hard consistency. The second case demonstrates the management of a retained root
      tip via a guided bone regeneration technique when it is detected prior to or
      during implant placement. Finally, a systematic therapeutic approach is proposed
      based on 17 case reports on implant periapical lesion management.

PMID- 15506024
TI  - Prevention of alveolar ridge deformities and reconstruction of lost anatomy: a
      review of surgical approaches.
AB  - Prevention and treatment of alveolar ridge deformities aim at preserving and/or
      reconstructing soft and hard tissues of the edentulous ridge. Different surgical
      techniques may be used to prevent ridge collapse before tooth extraction or to
      reconstruct lost ridge anatomy before tooth replacement. In cases of mild or
      moderate ridge defects, soft tissue augmentation is generally sufficient to
      repair the deformity. On the other hand, hard tissue augmentation should be
      selected primarily when implant therapy is scheduled. In cases of severe ridge
      defects, a staged or a combined approach may be appropriate. This article reviews
      the various approaches for the prevention and treatment of ridge deformities.

PMID- 15506025
TI  - Computer-aided direct all-ceramic crowns: preliminary 1-year results of a
      prospective clinical study.
AB  - The objective of this study was to investigate the clinical performance of: (1)
      adhesively placed Cerec crowns with reduced stump preparations, and (2) Cerec
      endo crowns. The crowns were examined at baseline using modified USPHS criteria
      in 20 patients with 10 Cerec crowns with reduced stump preparations and 10 Cerec
      endo crowns. All crowns had been produced chairside with the Cerec 3 CAD/CAM
      method using the function mode. The crowns were machined from Vita Mk II
      feldspathic ceramic blocks, polished manually, and placed with dual-curing
      composite luting agent using a functional adhesive. After 1 year, a follow-up
      examination of the crowns was conducted; all 20 Cerec crowns were rated with a
      clinically acceptable A or B rating. Fractures or loss of retention were not
      observed. The method of producing and placing all-ceramic crowns with reduced
      stump preparations and endo crowns chairside in one appointment can be
      implemented successfully in private practice.

PMID- 15506026
TI  - Spontaneous correction of pathologic tooth migration and reduced infrabony
      pockets following nonsurgical periodontal therapy: a case report.
AB  - This case report describes the spontaneous correction of pathologic tooth
      migration and reduced infrabony pockets after nonsurgical periodontal therapy. A
      3-mm diastema between the maxillary incisors was closed completely, and the
      mandibular teeth, which had migrated pathologically, returned to the optimal
      position. Clinical evaluation showed a significant reduction in probing depth,
      with increased clinical attachment and bone deposition demonstrated
      radiologically.

PMID- 15506027
TI  - Light transmission of posts and cores used for the anterior esthetic region.
AB  - Restoration of endodontically treated teeth is a routine procedure in everyday
      clinical practice. Placement of posts and cores is often required for replacement
      of the missing coronal aspect of teeth. Use of traditional post-and-core systems
      (gold and titanium) in conjunction with all-ceramic restorations results in poor
      esthetics because of the reflection and lack of light transmission. For a highly
      esthetic outcome, there is a need to use a material that transmits and refracts
      light in much the same manner as a natural tooth. The purpose of this study was
      to clinically evaluate the light transmission of a (1) ceramic post (Celay), (2)
      polyester post reinforced with zirconium fibers (Snowlight), and (3) zirconia
      post (Cosmopost), in comparison with a cast-metal post and core covered with
      opaque porcelain (control). The light transmission of these systems when used in
      conjunction with IPS Empress all-ceramic crowns was evaluated.

PMID- 15506028
TI  - A technique to remove epulis: case reports.
AB  - The purpose of this study was to describe an alternative surgical approach to
      removing epulis while preserving and improving the mucogingival complex. After
      scaling and root planing, six patients underwent surgical treatment to remove the
      growths. A subepithelial connective tissue graft was interposed between the bone
      and epulis using a pedicle flap. The lesion was always preserved. The epulis
      disappeared after several months, with minor variations in healing time among
      patients. At 60-month follow-up visits, all patients exhibited good gingival
      health, with no recurrence.

PMID- 15506029
TI  - Comparative study of enamel matrix derivative with or without GTR in the
      treatment of class II furcation lesions in dogs.
AB  - Chronic Class II furcation lesions were created in four dogs. After 21 days,
      group I remained as a control, group 2 was treated with membranes and enamel
      matrix derivative (EMD), and group 3 received EMD alone. Healing in group 1 was
      characterized by a long junctional epithelium and discrete bone formation; group
      2 showed reduced bone formation; and group 3 showed significant bone regeneration
      (area of new bone = 67.36%+/-3.93%; distance from furcation roof to bone crest =
      0.57+/-0.15 mm). The EMD led to significant regeneration of the furcation
      lesions, and the association with membranes was detrimental.

PMID- 15506030
TI  - The Papilla Presence Index (PPI): a new system to assess interproximal papillary
      levels.
AB  - The present article describes a classification system used to assess the
      interdental papillary height on natural teeth; the index can also be used in
      cases of lack of contact points and presence of diastemata. This system is
      particularly useful to define the loss of the interdental papilla because of
      periodontal disease and papilla reconstruction after periodontal treatment,
      particularly if tooth repositioning is involved. The index, based on esthetic
      evaluations, measures interproximal soft tissue height in relation to the CEJ,
      adjacent teeth, and the point corresponding to the ideal contact point. The four
      index scores are useful for an easy clinical assessment with respect to patient
      esthetics.

PMID- 15506031
TI  - Intercompartmental fluid volume shifts during cardiopulmonary bypass measured by
      A-mode ultrasonography.
AB  - To investigate the time course of fluid extravasation during cardiopulmonary
      bypass (CPB), we measured the peripheral tissue thickness (TT) by A-mode
      ultrasound in 34 patients undergoing elective cardiac surgery. TT of the forehead
      was determined by a handheld A-mode ultrasound device and 10 MHz Transducer at
      nine defined intervals, from the night before surgery until the first
      postoperative day. Mean calculated loss of 1700 +/- 40 mL (SEM) water during the
      fasting period resulted in a significant reduction of TT by 0.28 +/- 0.03 mm.
      From induction to start of CPB, rehydration with 1000 mL of fluid was performed
      and TT increased to baseline. After 60 min of extracorporal circulation, forehead
      TT increased significantly by 0.75 +/- 0.08 mm and remained unchanged until the
      end of surgery when the measured fluid gain was 1580 +/- 138 mL. At discharge
      from ICU, negative fluid regimen resulted in a balance of -127 +/- 146 mL whereas
      TT declined significantly to +0.16 +/- 0.09 mm compared to baseline. Dehydration
      due to fasting and the marked interstitial fluid extravasation during CPB could
      be detected by the changes of the peripheral TT. We conclude that parts of the
      fluid load during CPB are shifted from the intravascular compartment to the
      interstitial space in a time-dependent manner.

PMID- 15506032
TI  - Argatroban as an alternative to heparin in extracorporeal membrane oxygenation
      circuits.
AB  - We investigated the anticoagulant effects of argatroban, a direct thrombin
      inhibitor, versus heparin in extracorporeal membrane oxygenation (ECMO) circuits.
      Three sham circuits were prepared according to our hospital's standard practice
      and run for six hours simultaneously. Two circuits were anticoagulated with
      argatroban (one with heparin in the wet prime and one without). One circuit had
      heparin in the initial prime and was then anticoagulated with heparin. We
      measured thrombin generation (prothrombin fragment 1+2, D-dimer and thrombin
      antithrombin complexes), activated clotting times (ACTs) and partial
      thromboplastin times (aPTTs), and monitored thrombus formation using
      thromboelastography. ACTs were >1000 s in each circuit throughout assessment. No
      clot initiation was detected by thromboelastography. Thrombin generation was
      decreased in circuits anticoagulated with argatroban versus heparin, despite
      aPTTs being less prolonged. These results suggest that argatroban may be more
      efficacious than heparin for anticoagulation in ECMO. Additional studies are
      warranted to further evaluate argatroban in this setting.

PMID- 15506033
TI  - Measurement of the activated clotting time during cardiopulmonary bypass:
      differences between Hemotec ACT and Hemochron Jr apparatus.
AB  - BACKGROUND: Measurement of the activated clotting time (ACT) represents a
      standard method for coagulatory assessments. The test employs specific agents to
      trigger the coagulation process. The present study aimed to compare kaolin
      (Hemotec) versus a combination of silica, kaolin and phospholipid (Hemochron Jr)
      ACTs. METHODS: Hemotec and Hemochron Jr ACT monitors were compared by
      simultaneous measurement of paired arterial blood samples (n = 114) with respect
      to precision and bias during clinical conditions of cardiopulmonary bypass (CPB).
      The influence of haemodilution on the ACT was tested in an ex-vivo model.
      RESULTS: The precision of Hemotec and Hemochron Jr ACT measurements attained 21
      +/- 2.6 s versus 27.0 +/- 2.6 s (p = 0.126) during CPB and 2.5 +/- 2.2 s versus
      9.4 +/- 6.9 s (p = 0.000) after protamine administration, respectively. The
      Hemochron Jr monitor was associated with a bias of -102 +/- 13.7 s compared to
      the Hemotec ACT monitor (p = 0.000) during CPB and -6.9 +/- 2.9 s after protamine
      (p = 0.025). Linear regression analysis of ACT readings between monitors reached
      r = 0.526 (p = 0.000). Hemochron Jr ACT values correlated with the erythrocyte
      volume fraction r = 0.379 (p = 0.000). Ex-vivo data indicated that the Hemotec
      ACT monitor was associated with relatively higher ACT readings after
      haemodilution. CONCLUSION: The ACT is not a standardized measure. Test results
      are strongly associated with the specific compounds used to initiate the
      coagulation process.

PMID- 15506034
TI  - External validation of compliance to perfusion quality indicators.
AB  - PURPOSE: There exists a significant gap between the expected and delivered level
      of quality received in America's hospitals. As a result, clinical outcomes of
      critical services such as coronary artery bypass graft (CABG) surgery have
      received unparalleled scrutiny. Medical information technology companies like
      Solucient and insurance carriers such as Blue Cross of California have identified
      and published a list of hospitals that demonstrate superior quality and patient
      outcomes for CABG procedures. These 'benchmark' programs serve as a reminder that
      closing the quality gap is possible. Unfortunately, none of these rankings
      (report cards) provide programs that fail to achieve benchmark status with
      detailed information on the processes or methods necessary to improve
      performance. METHOD: After identifying hospitals within the Fresenius Medical
      Care Extracorporeal Alliance (FMCEA) system that were judged as top performers
      (benchmark programs) by either Solucient ('100 Top Cardiovascular Hospitals',
      Evanston, IL 60201) or Blue Cross of California ('Centers of Expertise', Newbury
      Park, CA 91320), 12 months of continuous collection of CPB-related quality
      indicator data were analyzed for compliance to the FMCEA evidence-based Quality
      Indicator Program (QIP). A comparison of compliance to the FMCEA CPB indicators
      was made between the benchmark FMCEA hospitals and the FMCEA peer group
      hospitals. RESULTS: Seven CPB process indicators were compared: 1) lowest
      sustained mean arterial pressure, 2) lowest sustained cardiac index, 3) lowest
      sustained mixed venous oxygen saturation, 4) lowest sustained hematocrit, 5)
      lowest activated clotting time, 6) highest sustained arterial blood temperature
      and 7) average sodium bicarbonate administered. Analysis of hospitals in the
      FMCEA system designated by Blue Cross of California as 'Centers of Expertise'
      revealed statistically significantly greater compliance (p < 0.05) in all but one
      CPB indicator. Hospitals in the FMCEA system designated by Solucient's '100 Top
      Cardiovascular Hospitals' listing revealed statistically significantly greater
      compliance to all but three CPB quality indicators. CONCLUSIONS: Successful
      compliance with the majority of FMCEA CPB process indicators correlates with
      external recognition from two report card systems demonstrating superior hospital
      performance. Analysis of compliance to process indicators may provide useful
      guidelines to improve the standard of care in CABG surgery in many hospitals.

PMID- 15506035
TI  - Management of continuous venous gas emboli during extracorporeal life support
      utilizing the Kolobow gas trap.
AB  - Extracorporeal life support (ECLS) with a roller pump system uses a closed
      cardiopulmonary bypass (CPB) circuit not equipped with a venous reservoir. Hence,
      gas emboli cannot escape the ECLS circuit, predisposing to clot formation,
      membrane failure and potential gas embolism. Rarely, some patients may develop a
      continuous release of gas into the venous circulation from multiple sources. Two
      pediatric ECLS cases are presented with continuous venous gas embolism. A 'gas
      trap' was devised by creating a column of fluid erected vertically on the venous
      line. This allowed gas to rise within the column, separating it from the ECLS
      circuit, thus, preventing gas from lodging in the membrane.

PMID- 15506036
TI  - A novel extracorporeal kidney perfusion system: a concept model.
AB  - The number of patients awaiting kidney transplantation has more than doubled in
      the past decade while the number of available donor organs has seen only a modest
      increase, leading to a critical shortage of organs. In response to this extreme
      shortage, the criteria for accepting organs have been modified to include
      marginal donors such as non-heart beating donors (NHBD). In these kidneys,
      determining viability is important for success of transplantation. Therefore, a
      study was undertaken to develop a system that would allow the extracorporeal
      assessment of function and compatibility of the donor organ before the patient is
      exposed to the risks associated with surgery. Following bilateral nephrectomy,
      the kidneys of 10 pigs (approximately 30 kg) were connected to a commercially
      available hypothermic pulsatile kidney perfusion apparatus. This system was
      modified to allow for normothermic pulsatile renal perfusion using the potential
      recipient's blood, via vascular access. These kidneys were perfused with the
      animal's blood for a minimum of two hours while various parameters were
      monitored. Perfusion pressures were kept between 60 and 90 mmHg, which correlated
      to flows between 70 and 150 mL/min. A decrease in perfusion pressure with a
      concomitant rise in flow over the two-hour period served as a good predictor of a
      viable and compatible graft. The modified kidney preservation system allows the
      normothermic, pulsatile extracorporeal perfusion of donor kidneys with the
      ability to monitor resistance to flow and urine production. This model also
      allows observation of the kidney for signs of hyperacute rejection. Further
      research needs to be conducted in order to determine if the system represents a
      methodology to increase the pool of available donor organs.

PMID- 15506037
TI  - Refractory ventricular fibrillation in accidental hypothermia: salvage with
      cardiopulmonary bypass.
AB  - A 20-year old woman presented with prolonged refractory ventricular fibrillation
      and pulmonary oedema following hypothermia while she was under self-administered
      heroin in an attempt to commit suicide. She was successfully resuscitated with
      cardiopulmonary bypass for core rewarming and internal defibrillation.

PMID- 15506038
TI  - Ex vivo evaluation of a new neonatal/infant oxygenator: comparison of the Terumo
      CAPIOX Baby RX with Dideco Lilliput 1 and Polystan Safe Micro in the piglet
      model.
AB  - OBJECTIVE: A newly developed neonatal and infant oxygenator with a nonheparin
      biocompatible polymer coating, low priming volume (43 mL), high oxygen transfer,
      wide operating range (<1.5 L/min) and low pressure drop represents a promising
      solution for cardiac surgery in neonates and infants. We compared the new CAPIOX
      Baby RX, Terumo (BRX) with two commonly used neonatal oxygenators: Dideco
      Lilliput 1 (DL1) and Polystan Safe Micro (PSM) in a piglet model. METHODS:
      Fifteen piglets (5.6 +/- 1.3kg) were placed on standardized cardiopulmonary
      bypass (CPB) for 6 hours using one of the three oxygenators (n = 5 in each
      group). After 120 min, the system was cooled to 25 degrees C for 60 min and then
      returned to normothermia. Arterial and venous blood gas data and temperature were
      recorded continuously by a CDI500 System (Terumo). Pressure drop, FiO2 and gas
      flow were recorded. Blood samples were taken before CBP, after 10 min, before and
      after cooling, and at the end. Total blood counts, thrombin-antithrombin complex
      and plasma-free haemoglobin (PfHb) were measured. RESULTS: All oxygenators showed
      acceptable performance for the duration of CPB. The BRX had lower mean gas flow
      (0.33 +/- 0.05 L/min) and FiO2 (0.43 +/- 0.02%) throughout CPB than the DL1 (1.14
      +/- 0.25 L/min, p = 0.006 and 0.60 +/- 0.02%, p = 0.009, respectively) or the PSM
      (1.47 +/- 0.87 L/min and 0.54 +/- 0.08%, p = ns). Pressure drop in the BRX group
      ranged from 12 to 22 mmHg. This was significantly lower than in the DL1 group (39
      65 mmHg, p = 0.005). In the PSM group, values ranged between 24 and 33 mmHg (p =
      ns). The increase in PfHb at six hours was significantly lower in the BRX (11.3
      +/- 4.2 ng/dL) versus the DL1 (42.2 +/- 6.1 ng/dL, p = 0.004) and the PSM (56.7
      +/- 15.5 ng/dL, p = 0.045). CONCLUSIONS: The BRX is as safe as the DL1 and the
      PSM, with superior performance in pressure drop, efficient blood gas management
      and lower haemolysis. The BRX exhibited the lowest prime, hold-up volume and
      breakthrough time.

PMID- 15506040
TI  - Epidemiology and acute care of migraine headache.

PMID- 15506039
TI  - Quantitative haemodynamic evaluation of aortic cannulas.
AB  - We have designed a new type of aortic cannula for extracorporeal circulation
      which we hypothesize has superior haemodynamic characteristics compared with
      existing types. The aim of the study was to perform a quantitative evaluation of
      the haemodynamic performance of commercially available aortic cannulas against
      our new design. Six existing cannulas and two self-designed, modified DLP
      cannulas were investigated. Pressure drop, peak velocity and wall thickness were
      obtained from in vitro experiments. Pressure drop and turbulent stresses were
      obtained by in vivo experiments. At 5 L/min the pressure drops of the new design
      were 18-25 mmHg in vitro and 20 mmHg in vivo compared with 25-92 mmHg in vitro
      and 28-90 mmHg in vivo for the six commercially available cannulas. Turbulent
      stresses of the new design varied between 25 and 50 N/m2 in vivo compared with
      125-500 N/m2. Both in vivo and in vitro results showed a clear haemodynamic
      superiority of the new cannula-tip design compared with all existing types.

PMID- 15506041
TI  - Preventing migraine pharmacologically.

PMID- 15506042
TI  - An integrated management program for migraine: the Kaiser experience.

PMID- 15506043
TI  - [Botulinum toxin treatment -- state of the art 2000].

PMID- 15506044
TI  - [Pharmacology of botulinum neurotoxin type A].
AB  - The efficacies and potencies of Dysport and Botox, botulinum neurotoxin type A
      complexes approved for therapy, were investigated under various conditions.
      Conditions for maximal expression of biological activities of both commercial
      products were explored in vitro in the phrenic nerve-hemidiaphragm preparation
      whilst conditions for optimal distribution of Dysport were tested in vivo in a
      double blind trial involving volunteers, using the foot Muscles extensor
      digitorum brevis. Whilst Dysport and Botox expressed the same potency in vitro
      when albumin was added, their potencies markedly departed from each other when
      the products were reconstituted as recommended by the manufacturer. The
      biological availability of Dysport could be enhanced in vivo by (1) lowering its
      concentration, (2) supplementing with albumin and (3) increasing the injection
      volume. Thus, Dysport can be recovered more efficiently by deviating from the
      manufacturer's recommendations allowing a more economical use of Dysport.

PMID- 15506045
TI  - [Treatment of focal dystonia with botulinum toxin A].
AB  - Local injections with Botulinum toxin A (BtxA) are safe and effective in the
      treatment of focal dystonia. In cervical dystonia and blepharospasm, BtxA
      injections have become the treatment of choice. However, good results have also
      been reported with oromandibular dystonia, spasmodic dysphonia and writer's
      cramp. In cervical dystonia, muscles for injection are selected by clinical
      presentation or in complex forms with EMG guidance. Several studies have shown
      that 500 units Dysport are safe and effective in the treatment of cervical
      dystonia. In blepharospasm, injections are performed in the periorbital part of
      the orbicularis oculi muscle with good results for 12-14 weeks. The most
      frequently employed starting dose is 120 units Dysport per eye, divided in three
      periorbital injection sites. In case of levator inhibition, the pretarsal part of
      the orbicularis oculi muscle should be injected in a lower dose. EMG guidance is
      not necessary. By contrast, BtxA treatment of spasmodic dysphonia and writer's
      cramp require EMG-guided injections in order to avoid side-effects. Dose
      recommendations for the various types of dystonia are given in the text. In up to
      5% of patients with dystonia, the development of neutralising antibodies is
      reported following repetitive injections with BtxA. Patients with antibodies had
      a shorter interval between injections, more "boosters", a higher dose per 3-month
      interval, and a higher total dose injected. In case of neutralizing antibodies
      against the A toxin, the treatment with Botulinum toxin B (Neurobloc) is a
      possible alternative.

PMID- 15506047
TI  - [Botulinum toxin type A treatment of upper limb spasticity].
AB  - In recent years, local injections with Botulinum toxin type A (BtxA) have become
      the treatment of choice for dystonia. However, several studies have demonstrated
      its efficacy and safety in the treatment of focal spasticity as well. These
      studies have shown efficacy and safety in upper limb spasticity treatment at a
      total dose between 500 and 1500 units of Dysport per injection session. While
      injections in upper arm muscles are easily administered without EMG-guidance, we
      recommend EMG-guidance for lower arm and finger muscles. In addition to
      functional improvement, BtxA treatment may also be considered for the following
      reasons: treatment of spasticity associated pain or painful muscle spasms,
      improved hygiene, facilitation of care, prevention of skin breakdown, and
      improved positioning of the upper limb. The definition of a realistic treatment
      goal, in agreement with the patient, as well as adjunctive physiotherapy are
      prerequisites for a successful BtxA treatment. Dose recommendations are given in
      Table 1.

PMID- 15506046
TI  - [Measuring outcome in spasticity rehabilitation].
AB  - Spasticity is a frequent consequence of upper motor neuron lesion and is
      associated with a variety of symptoms such as pain, muscle stiffness and reflex
      patterns that interfere with activities of daily living, dexterity and gait. As
      therapy strategies in managing spasticity-associated problems have been evolving
      there is an increasing need for a practicable documentation system which
      describes spasticity and related symptoms on different levels in order to
      evaluate especially the level of functioning. In daily routine the single-case
      design reflects a useful technique to evaluate the status in terms of technical,
      functional and individual goals for treatment. However, there is no single tool
      to measure the different types of changes due to treatment, therefore a variety
      of selecting tests, based on the functional changes expected from the selected
      treatment, is recommended. The sensitivity of the selected tests should match the
      range of expected improvements related to the specific treatment. Technical goals
      should be evaluated by validated spasticity rating scales. As changes in
      technical measures of spasticity such as muscle tone, muscle length, range of
      motion or repetitive voluntary movements may not correlate with clinical
      improvements, individual functional goals should be defined. Those functional
      goals should reflect the patients' and care-givers' individual perception of the
      actual problem. A treatment diary is a useful tool to document subjective
      perception of changes over time. Some practical issues are adressed below.
      Reliable outcome measures enable patients and doctors to select further treatment
      strategies and gives health care providers information on treatment expectations
      in return for their investments.

PMID- 15506048
TI  - [Botulinum toxin treatment of hip adductor spasticity in multiple sclerosis].
AB  - Spasticity results in a resistance to passive movement and decrease of passive
      mobility of the involved joints and is defined as a state of hypertonicity with
      exaggeration of tendon reflexes mediated by a loss of inhibitory control of upper
      motor neurons. In patients with severe stages of multiple sclerosis (MS)
      spasticity of the lower limbs often leeds to a spastic pattern with hip adduction
      resulting in decreased range-of-motion (ROM), increased pain, spasms, and
      functional disability (disturbed gait and sitting position) as well as
      difficulties with perineal hygiene. Local botulinum toxin type A (Btx-A)
      injections in spastic muscles offer a new treatment approach for managing
      spasticity and associated problems. Up to now Btx-A is approved for the treatment
      of blepharospasm and cervical dystonia and the treatment of equinous gait in
      children with cerebral palsy in Austria and Germany. Up to now only in
      Switzerland Botox is licensed for the treatment of focal spasticity. Btx-A is a
      neurotoxin derived from Clostridium botulinum. In most european countries Btx-A
      is available as Dysport (vial = 500 units) and Botox (vial = 100 units). In
      prospective studies a ratio of 1 unit Botox to 3-4 units Dysport was found.
      Following intramuscular injection Btx-A blocks the release of acetylcholine at
      the neuromuscular junctions, thereby inhibiting muscle contraction, and decreases
      spastic muscle tone and muscle spindles afferent information to the spinal cord.
      The spectrum of side effects includes local weakening of the injected and
      adjacent muscles as well as pain and haematoma at the injection site. At
      therapeutic doses side effects are local and transient. According to a double
      blind, placebo controlled, dose ranging study published by Hyman et al. (2000,
      Dysport in a dose of 500, 1000 and 1500 units reduced the degree of hip adductor
      spasticity associated with MS, and this benefit was evident despite concomitant
      use of oral antispasticity medication. According to the results of the study
      there was a clear trend towards greater efficacy and duration of effects with
      higher doses of Dysport. Taking efficacy and adverse events into account
      (incidence of muscle weakness was higher for the 1500 units group than for
      placebo) the optimal dose for hip adductor spasticity seems to be 1000 units
      Dysport divided between the adductor magnus, longus and brevis muscles and
      between both legs. To increase Btx-A effects following injection of hip adductors
      additional physiotherapy and casting or orthosis to increase passive hip
      abduction is recommended. According to the literature anatomical localisation of
      the adductor muscles for injection and aspiration following insertion of the
      needle, to avoid injection of the toxin into a vessel, should be performed. A
      maximum dose of 1500 units Dysport (400 units Botox) per treatment session and
      250 units Dysport (50 units Botox) per injection site is recommended. See table
      for dose-range of Dysport, and Botox in the treatment of adult patients with hip
      adductor spasticity. For evaluation of treatment effects in hip adductor
      spasticity clinical examination with specific scales and measurements (see
      Appendix) at baseline, 4 and 12 weeks following BtxA injection is recommended:-
      Global rating of severity (0-4; patient's self assessment and physician's rating)
      --Global rating of response (-4 - +4; patient's self assessment and physician's
      rating)--Visual Analogue Scale (patient's self assessment of pain)--Active and
      passive ROM (manual goniometer)--Distance between the medial femur condyles in
      thigh extension (distance in cm)--Modified Ashworth scale (0-4)--Ten meter
      walking time (seconds)--Functional Ambulation Categories (0-5)--Score of perineal
      hygiene (0-5).

PMID- 15506049
TI  - [Treatment of the spastic drop foot with botulinum toxin type A in adult
      patients].
AB  - Spastic drop foot can be managed by physical measures, local pharmacological
      agents, oral anti-spastic drugs and surgical procedures. Recent studies have
      documented the clear effect of botulinum toxin type A (BTX-A) in the treatment of
      the spastic drop foot, particularly by reducing the resistance against passive
      movement and increasing the range of motion. Functional benefit and pain
      reduction have also been observed. The use of BTX-A is safe and free of serious
      side effects. Individual realistic treatment goals must be defined by the
      rehabilitation team before the treatment. Possible purposes of the treatment are
      the achievement of a straight foot to allow weight bearing or application of an
      orthosis and to reduce the premature activation of the calf muscles during gait.
      Other treatment goals are the facilitation of nursing care, as well as physical
      and occupational therapy. BTX-A injections can reduce pain, and prevent pressure
      ulcers or surgical interventions. Early physiotherapy or occupational therapy may
      increase the treatment effect of BTX-A. Close cooperation between the
      neurologist, physiotherapist, occupational therapist, nursing staff and other
      multidisciplinary rehabilitation team members is essential to maximize the
      benefit for the patients.

PMID- 15506050
TI  - [Botulinum toxin type A in the treatment plan for cerebral palsy].
AB  - Over the past decade a number of placebo-controlled studies have confirmed that
      intramuscular injections of botulinum toxin A (BTX A) has antispastic effects.
      Cerebral palsy is among the most frequent disorders of the growing locomotor
      apparatus during childhood. Weakness as well as spasticity due to lack of
      selective neuronal control causes functional impairment and additional mechanisms
      of compensation, retardation of motor development, secondary deformities of
      muscles and soft tissues due to a failure of muscle growth,
      subluxation/dislocation of joints, early osteoarthritis, and pain. Prevention of
      this vicious circle has to be the main goal of caring for children with
      spasticity. Quality of life in children with cerebral palsy can be improved by
      support of their daily living motor activities. Increased muscle tone can be
      reduced by physical exercises, by individually adapted orthoses, walkers, and
      wheelchairs, by manual therapy, serial casting and in certain cases by systemic
      drugs or by multiple-stage surgical procedures. BTX A can be used to enable these
      treatment possibilities or to increase their effect. In our clinical study (BTX A
      in 114 patients in 19952/2000) we found no major side effects. Weakness, pain or
      swelling occurred temporarily. Indications for the use of BTX A are pain,
      functional impairment, severe cosmetic problems, as well as prevention of
      secondary contractures, deformities, and dislocations caused by increased muscle
      tone. We consider the selection of patients for the use of BTX A and the
      development of a goal-orientated treatment plan by multidisciplinary team
      approach as the most important steps. Prerequisites are exact statomotoric and
      dynamic physical examinations, and standardised movement analysis. 3-D-gait
      analysis and dynamic electromyography is used in cases where functional
      improvement of gait is the goal of BTX A-treatment.

PMID- 15506051
TI  - [Botulinum toxin in the treatment of focal hyperhidrosis].
AB  - INTRODUCTION: Botulinum A toxin (BTX-A) acts primarily at peripheral cholinergic
      synapses, inhibiting the release of acetylcholine. Initially it has been used to
      block the neuromuscular junction in focal dystonic and spastic syndromes.
      Recently there has been suggestions for potential clinical indications in non
      muscular diseases where cholinergic terminals play a role. GUSTATORY SWEATING: In
      1995 physicians reported a long-lasting anhidrotic effect of intracutaneous BTX-A
      injections in patients suffering from gustatory sweating (Frey's syndrome).
      Consequently, a number of clinical studies demonstrated good efficacy of
      intradermal injections of botulinumtoxin in patients with focal hyperhidrosis.
      FOCAL HYPERHIDROSIS OF THE PALMS AND AXILLAE: Focal hyperhidrosis is usually
      confined to the palms and axillae. Excessive sweating may be a social handicap
      and an occupational hazard. The management of focal hyperhidrosis remains
      controversial. Topical antiperspirants are only effective in very mild cases.
      Iontophoresis with tap water or anticholinergic drugs is messy and time consuming
      with only short-lived effect. Sympathectomy, the cornerstone of surgical
      management, is usually effective in palmar hyperhidrosis. Complications of this
      technique include surgical risks, postoperative and cosmetic problems and
      compensatory hyperhidrosis. AXILLARY HYPERHIDROSIS: Several studies confirmed
      that intracutaneous injections of botulinum toxin are useful in the majority of
      patients with axillary hyperhidrosis resistant to conventional treatment. In
      axillary hyperhidrosis total doses are ranging from 200-400 mU Dysport or from 80
      to 130 mU Botox to reach a good clinical response. Injections are usually well
      tolerated and no serious side-effects have been observed. The mean duration of
      anhidrotic effect ranges between 3 and 9 weeks. PALMAR HYPERHIDROSIS: The use of
      botulinumtoxin in patients with palmar hyperhidrosis is rather difficult. The
      therapeutic window is smaller because injections are complicated by transient
      weakness of the small hand-muscles. Furthermore the injections at the palms are
      painful which can be overcomed by application of local anaesthetics or the
      blockade of the ulnar and median nerves. The duration of anhidrotic effect ranges
      from 20 to 50 weeks. CONCLUSION: Intracutaneous injections of botulinum-toxin
      should be offered to patients with focal hyperhidrosis of the palms and axillae
      causing serious social, psychologic and occupational problems, resistant to other
      conventional treatment options.

PMID- 15506052
TI  - [Reimbursement strategies for botulinum toxin type A in Austria].
AB  - In the last two decades, botulinum toxin A (BtxA) has become the treatment of
      choice for spasmodic torticollis, blepharospasm and hemifacial spasm. Since 1999
      Dysport and Botox are approved in Austria for the treatment of these indications.
      BtxA is applied in the hospital (out- and in-patient clinics) and by specialists
      (especially neurologists) in private practices. Complete reimbursement of the
      costs by the health insurance is provided only if the treatment has taken place
      in the specialist's private practice. The costs of BtxA application in the
      hospital are partially covered by the so called "LKF points" (Austrian system for
      reimbursement of costs in the hospital) or by the flat rate fee for out-patients.
      Approval for other indications for BtxA is expected in the next years, therefore
      appropriate cost reimbursement for BtxA is of immense importance. Different
      reimbursement systems are discussed in the following article. It seems useful to
      adopt approved procedures in special situations, such as reimbursement for the
      ambulatory application of chemotherapy and Betainterferon in Austria. The
      appropriate reimbursement system has to consider the indication and documentation
      of Btx-treatments as well as the qualification of the Btx-user.

PMID- 15506053
TI  - [Botulinum toxin in Austria and neighboring countries].

PMID- 15506054
TI  - [A year of recommendations].

PMID- 15506055
TI  - [Role of nitric oxide in the NKCC2 hyperactivity of Dahl "salt-sensitive" rats].
AB  - Renal NaCl reabsorption is increased in Dahl "salt-sensitive" (DS) rats, due to
      an increased activity of the Na-K-Cl cotransporter NKCC2. On the other hand,
      nitric oxide (NO) is an inhibitor of NKCC2 and a deficient nitric oxide synthase
      (NOS) seems to play an important role in salt-sensitivity of DS rats. Here, we
      investigated the hypothesis that NKCC2 hyperactivity in DS rats is due to a
      deficient NOS, via the interactions cyclic GMP (cGMP)/cyclic AMP (cAMP) at the
      level of the thick ascending Henle's loop (TAL). DS rats DS (males, 250-300 g)
      and their normotensive controls DR ("salt-resistant") are sacrificed, the kidneys
      removed and NKCC2 activity is measured in medullary TAL (mTAL) as previously
      described. Medullary contents of NO are measured with a NitroFlux analyser by
      heat-reduction of nitrates and nitrites to NO. AMPc levels in mTAL are measured
      by an EIA immunotest. Neither L-NAME (3 mM), nor L-arginine were able to modify
      NKCC2 activity in mTAL from DS (pre-hypertensive) or DR rats. Levels of NO in the
      medullary interstitium and AMPc in mTAL were not significantly different between
      DS and DR rats. Conversely, in DS rats charged with 2% salt (in the food) during
      7 weeks, L-arginine significantly inhibited NKCC2 in DS (35.6 +/- 6.8 vs 25.3 +/-
      4.9 nmoles/mg protein/min; p<0.05 non-paired Student's t-test), but not in DR
      rats. In conclusion, NKCC2 in our mTAL preparation of prehypertensive DS and DR
      rats is insensitive to L-NAME and L-arginine. This suggests the absence of a
      functional NOS. NKCC2 hyperactivity of prehypertensive DS is therefore not due to
      a deficient NOS. This was confirmed by the normal levels of interstitial NO and
      mTAL cAMP in prehypertensive DS rats. Finally, a salt-load seems to induce NOS
      expression in mTAL of DS rats. This last observation deserves further
      investigation.

PMID- 15506056
TI  - [Effect of fish protein on blood pressure, glycemia and plasma and urinary
      parameters in spontaneously hypertensive rats (SHR) and diabetic SHR].
AB  - Fish protein (FP) effect compared to casein (CAS) was studied on blood pressure
      (BP) evolution and glycemia in part, and on plasma lipid, angiotensine II and
      aldosterone concentrations and urinary aldosterone on the other hand, in SHR and
      in SHR with streptozotocin-induced diabetes (SHR-STZ). Two groups of rats (6 SHR
      and 6 SHR-STZ) were fed for 2 months diet containing 20% CAS or 20% FP. One month
      before sacrifice, diabetes was induced into one group of rats by a single
      intraperitonealy injection of streptozotocin (STZ). The results showed that FP
      diminished blood pressure (-9%) in SHR, compared with CAS. In contrast, FP
      enhanced significantly blood pressure in SHR-STZ vs SHR (p<0.01). There was no
      effect on glycemia with fish protein. FP compared to CAS involved a diminution (
      41%) and (-17%) of total cholesterol and (-26%) and (-9%) of phospholipids in SHR
      and SHR-STZ, respectively. Moreover, a decrease of triacylglycerols (-21%) was
      noted in SHR-STZ with FP vs CAS. In SHR, plasma aldosterone and angiotensine II
      concentrations were reduced (-62%) and (-64%) and urinary aldosterone amounts
      were enhanced with FP compared to CAS (p<0.05). In SHR-STZ group, aldosterone
      value was fivefold lower in plasma and twofold higher in urine with FP compared
      to CAS. A significant enhancement of urinary aldosterone was noted in SHR-STZ vs
      SHR whatever diet-consumed. In conclusion, FP has a beneficial effect on blood
      pressure by modulating the hypertension markers i.e. plasma total cholesterol,
      angiotensine II and aldosterone, in SHR group, and on total cholesterol and
      triglycerids in SHR-STZ. FP reduces plasma aldosterone by its enhanced urinary
      excretion. It is necessary to specify the action mode of FP in order to propose
      it as nutritional complement in the degenerative diseases such as hypertension
      and diabetes.

PMID- 15506057
TI  - [Angiogenesis and arteriogenesis are increased in the SHR at the pre-hypertensive
      stage].
AB  - OBJECTIVE: A microvascular rarefaction by angiogenic deficiency could promote the
      onset of hypertension in SHR, in young hypertensive patients and in normotensive
      descendants of hypertensive parents. We studied the angiogenic potency in
      prehypertensive SHR, in fibrin chambers implanted in rats, an in vivo model of
      angiogenesis. METHODS: Four-week pre-hypertensive SHR (n=9) and controls WKY
      (n=9) were implanted with fibrin gel chambers. The chamber is a cylinder (dia.:
      13 mm; H: 5 mm) whose base is perforated with 10 holes of 0.8 mm. The chambers
      are filled with rat fibrin and implanted (n=4) into the rat dorsal subcutaneous
      space. After 14 days, vasculo-conjunctive buds have invaded the fibrin gel
      through the holes and the chambers are removed, fixed and coloured. The intact
      vascular buds were studied using optical microscopy. The number of vessels
      counted in central field corresponds to the vascular pedicle, the average number
      of vessels counted in 3 peripheral fields, represents the vascular branching. The
      number of arterialised vessels including at least 2 layers of SMC was counted in
      the central field of each bud. RESULTS: Both rat strains remained normotensive
      all along the experiment. In SHR fibrin chambers, the number of peripheral
      vessels (20 +/- 2.6 vs 9.5 +/- 3; p<0.0001) and the number of central
      arterialized vessels (7.5 +/- 2 vs 2.1 +/- 1.3; p<0.0001) was significantly
      higher compared to WKY. CONCLUSION: Angiogenesis and arteriogenesis are increased
      in pre-hypertensive SHR compared to WKY. These results plead against a
      microvascular rarefaction hypothesis in these genetically hypertensive rats.

PMID- 15506058
TI  - [Hand skin heating: a new method for the evaluation of conduit artery endothelial
      function in insulin-dependent diabetic patients].
AB  - The presence of an altered endothelium-mediated flow-dependent dilatation (FDD)
      of peripheral conduit arteries in insulin-dependent diabetic patients without
      microangiopathy is still controversial. We studied 10 normotensive and non
      atherosclerotic insulin-dependent diabetic patients (D group) without
      complication (neuropathy, microalbuminuria or neuropathy) and 10 control subjects
      (C group) matched for age, sex and BMI. Radial artery diameter (RAD,
      echotracking) and flow (RAF, Doppler) were measured at baseline and during FDD in
      response to distal hand skin heating (from 34 to 44 degrees C). a method
      developed to increase RAF by stable steps by decreasing gradually hand skin
      vascular resistance. Endothelium-independent dilatation was evaluated by
      administration of glyceryl trinitrate (GTN: 0.3 mg spray). At baseline, there was
      no difference between group for RAF (C: 18 +/- 5 vs D: 18 +/- 2 mL/min; NS) and
      RAD (C: 2.51 +/- 0.12 vs D: 2.54 +/- 0.07 mm; NS). Heating induced in the
      diabetic group a smaller increase in RAF (C: 473 +/- 126% vs D: 262 +/- 63%;
      p<0.05) and RAD (C: 22.6 +/- 2.6% vs D: 16.1 +/- 1.8%; p<0.01). This last result
      remains significant when the increase in RAF was included into the analysis of
      RAD variation during heating (p<0.05). GTN-induced dilatation was similar in the
      2 groups. Our results obtained by use of the hand skin heating method demonstrate
      the presence of an abnormal arteriolar skin reactivity and an altered peripheral
      conduit artery endothelium-dependent dilatation in uncomplicated insulin
      dependent diabetic patients. The early identification of these anomalies, with
      negative prognostic value, could contribute to the management of these patients.

PMID- 15506059
TI  - [Role of vagosympathetic balance in obesity-induced hypertension].
AB  - A sympathetic hyperactivity is a common feature in hypertension, type 2 diabetes
      (T2D), ageing and obesity-induced hypertension. This increase in sympathetic
      activity may lead to an elevation of arterial rigidity. By contrast, cardiac
      parasympathetic impairment is observed in these pathologies. Recently we showed
      in a model of rats with massive obesity (ventromedial hypothalamic lesions) that
      an enhanced vagal activity may be protective against hypertension. The aim of the
      present study was to evaluate the influence of an increase in sympathetic
      activity and a change in vagal activity on arterial rigidity and hypertension in
      T2D patients. Fourteen hypertensive T2D patients aged 54 +/- 2 years were
      compared to 22 elderly normotensive subjects (75 +/- 1 years: 11 controls and 11
      T2D) and 34 middle aged normotensive subjects (43 +/- 1 years; 17 controls and 17
      T2D). Cardiovascular vagosympathetic activity was investigated by spectral
      analysis of heart rate (HR) and blood pressure (BP) (Finapres) during 6 min at a
      controlled breathing rate (12 cycles/min). BP and the low frequencies of systolic
      BP (LF-SBP) were significantly (p<0.01) higher in hypertensive T2D and elderly
      patients. Pulse pressure (PP) and the high frequencies of HR (HF-HR) were lower
      in hypertensive T2D patients. PP was positively correlated to LF-SBP (r=0.58;
      p=0.03) only in hypertensive T2D patients. Diastolic BP was negatively correlated
      to HF-HR in elderly control subjects (r=-0.63; p=0.03) but not in hypertensive
      T2D patients. The present results suggest that: sympathetic nervous system
      activity is enhanced in subjects over 70 years without any aggravating effect of
      T2D and in middle-aged hypertensive patients with type 2 diabetes; the increase
      in pulse pressure, an index of arterial rigidity, in elderly subjects may result
      from sympathetic override; the decrease in the cardiac sympathovagal balance,
      mainly due to a high vagal activity, may be protective against the occurrence of
      hypertension in patients with type 2 diabetes.

PMID- 15506060
TI  - [Body composition and left ventricular geometry].
AB  - Left ventricular mass and cardiac output are, particularly in obesity, correlated
      with fat free body mass. We assessed the relationship between ventricular
      geometry and fat body mass in treated hypertensives with or without normalization
      of blood pressure We investigated 175 patients (age: 57 +/- 15 years, M/F:
      111/64, Mean blood pressure (MBP): 111 +/- 18 mmHg, BMI: 27.02 +/- 3.70 kg/m2:
      20.3-39.6 kg/m2) with measure of body composition (impedancemetry Analycor2) and
      echographic left ventricular mass (adjusted to height2.7: mass2.7). Multiple
      correlation with adjustment to age and MBP were performed in men (M) and in women
      (W). Mass2.7 is correlated with fat mass percentage in men (R partial R: 5.6,
      p=0.02). LV diastolic diameter is correlated with fat free body mass while
      interventricular septum is correlated with fat body mass but only in men. In
      summary, in hypertensives not selected on BMI or BP, fat body mass is weakly
      correlated to ventricular wall thickness in men, probably mediated by sympathetic
      tone, while fat free body mass is related to ventricular volume in both gender
      probably through the water volume particularly in vascular bed. In conclusion,
      both components of body composition are differently, and weakly, linked to
      ventricular geometry in hypertensive patients.

PMID- 15506061
TI  - [Is the white coat effect an alert reaction?].
AB  - Is the white coat effect an alert reaction? In this cross-sectional study we
      compared the white coat effect on systolic blood pressure with the systolic blood
      pressure reactivity obtained during a stress test. The influence of the
      sympathetic system (LF band of systolic BP) and the parasympathetic system (HF
      band of pulse rate) on white coat systolic blood pressure and stress test
      systolic blood pressure were analysed. We stratified 174 subjects into two
      groups, according to their blood pressure: hypertensives (HT, n=44, BP>140/90
      mmHg) and normotensives (NT, n=130). The BP was recorded during an occupational
      health consultation, over 24 hours, and beat to beat during a stress test
      (Finapress). White coat systolic BP was calculated as the difference between the
      consultation BP and the average systolic BP over 24 hours. The white coat
      systolic BP was not related with an increase in pulse rate. In contrast, during
      the stress test the increases in systolic BP and pulse rate were correlated
      (r=0.44; p<0.001). The white coat systolic BP was lower than the stress test
      systolic BP in the NT (6.6 +/- 7.2 vs 23 +/- 12 mmHg; p<0.001) and in the HT (16
      +/- 11 vs 29 +/- 17 mmHg; p<0.001). The HT had a lower parasympathetic index than
      the NT (0.45 +/- 0.43 vs 0.92 +/- 0.83 bpm2; p<0.001). In the HT the white coat
      systolic BP was positively correlated with the stress test systolic BP (r=0.47:
      p<0.01) and negatively with the parasympathetic activity index. In conclusion,
      for recently diagnosed and untreated HT an early alteration of the
      parasympathetic system reveals that the white coat effect is a low amplitude
      alert reaction.

PMID- 15506062
TI  - [Association between blood pressure level and the follow up of the guidelines
      concerning the use of self blood pressure measurement].
AB  - OBJECTIVES: To evaluate the characteristics of hypertensive subjects who practise
      self measurement of blood pressure (SMBP) and their conditions of use, and to
      identify the properties of subjects using SMBP according the usual guidelines.
      METHODS: In 531 consecutive hypertensive subjects, referred to hypertension
      specialists, possessing a SMBP a questionnaire evaluating the condition of use of
      SMBP was given. Subjects following the guidelines about the use of SMBP have been
      compared to those using SMBP without specific design of supervision. RESULTS: In
      this population, aged 62 +/- 14 years, with 57% of men and a mean blood pressure
      of 147 +/- 23/82 +/- 12 mmHg, the SMBP devices have been bought without medical
      advice in 50% of cases (265/531). In 45% of cases (239/531), SMBP were made at
      the wrist. SMBP device was used every days in 26% of cases, every weeks in 27% of
      cases, every month or more in 22% of cases and only in case of uneasiness in 25%
      of cases. Blood pressure was measured only in the morning in 25% of cases, in the
      morning and evening in 31%, only the evening in 8% and at any time of the day in
      36% of cases. More frequently 2 BP measurements were realized (47%) and in 19% of
      cases 3 measurements have been performed. In 15% of cases, the measurements were
      performed on 3 or 4 days consecutively, more frequently (85%) the measurements
      were realized without specific design ("once in awhile"). The data of SMBP were
      noted and showed to the doctor in 34% of cases. Only 12% (64/531) of subjects
      followed the usual guidelines concerning the use of SMBP (2 or 3 measurements, in
      the morning and the evening, during 3 or 4 consecutive days). Subjects following
      the guidelines for SMBP use have a higher SBP at the office than those using SMBP
      without specific design of supervision (155 +/- 25 mmHg vs 146 +/- 22 mmHg;
      p<0.01). CONCLUSION: Among hypertensives referred to hypertension specialists
      most of subjects use SMBP device without a specific design of supervision.
      Subjects with the most severe hypertension are those who have the best formation
      for SMBP.

PMID- 15506063
TI  - [Professional stress and blood pressure reactivity to stress do not predict blood
      pressure at 5 years].
AB  - High job strain has been reported to be associated with higher blood pressure.
      Job strain could lead to hypertension if individual perception of stress or
      cardiovascular reactivity to stress are high. We report the results of the first
      five-year follow up study, which aimed to assess the respective influences of
      perception of professional strain and cardiovascular reactivity to a mental
      stress test on BP. A cohort of 292 healthy subjects (mean +/- SEM, 38 +/- 1
      years) was followed for progression to hypertension outcome which was defined as
      an increase in SBP or DBP higher than 7 mmHg or a DBP higher than 95 mmHg during
      the follow-up. The high strain (HS) group representing 20.9% of the subjects was
      compared with the remaining subjects (NHS). Similarly the 20.9% subjects with the
      highest BP stress reactivity (HR) were compared with the remaining subjects
      (NHR). The Kaplan-Meier survival estimates revealed that neither high job strain,
      nor high stress reactivity, increased incidence of progression to hypertension.
      Age, alcohol, salt diet, BMI, and occupation did not interfere with our results.
      In conclusion, high stress cardiovascular reactivity and high job strain do not
      appear to be major risk markers for future high BP in healthy young adults.
      Stress could be associated with high BP at a short term and could explain high
      blood pressure in a long run only in stress-sensible subjects.

PMID- 15506064
TI  - [Clinic and morphologic evolution five years after a renal atherosclerotic artery
      stenosis (RAS): a study of twenty nine hypertensive patients population].
AB  - The indication of renal atherosclerotic artery stenosis revascularisation is
      always debated in clinical practices when arterial hypertension is stabilized by
      the treatment, especially if the stenosis is discovered fortuitously. The
      clinician needs clinical and morphological markers which will indicate or not the
      revascularisation in the situation of "nephronic protection". The benefits of
      angioplasty have been studied on the blood pressure, the creatinine clearance,
      the glomerular function analyzed by scintigraphy, the renal length and more
      recently on the mean cortical thickness (MCT). The follow-up of these studies is
      generally inferior to 2 years. In this work, we tried to estimate the clinic and
      morphologic evolution 5 years after a unilateral artery stenosis angioplasty.
      From a group of 249 patients who had a renal angioplasty between January 1995 and
      January 2000 (T0), 29 patients with refractory hypertension and with a unilateral
      atherosclerotic renal artery stenosis on spiral computed tomographic angiography
      (TCA) performed at T0 [17 M; 12 W; medium age 68.6 +/- 10 years] were included.
      The TCA performed at 5 years (T5) eliminated a new renal arterial stenosis or
      restenosis. We have analyzed 29 revascularized kidneys (kidney S) and 29
      controlateral kidneys (kidney C), the blood pressure and renal function. The
      renal length (mm) was at T0: kidney C=99.4 +/- 13.5; kidney S=93.5 +/- 10.8 and
      at T5: kidney C=99.4 +/- 12.6; kidney S=94.2 +/- 10.7. MCT (mm) was at T0: kidney
      C=7 +/- 1.2; kidney S=6.6 +/- 1.1 and at T5: kidney C=6.2 +/- 1.2; kidney S5=6 +/
      1. The cortical atrophy got worse while the renal length and creatinine
      clearance were stable: only diastolic blood pressure was controlled (78.8 mmHg +/
      11.9). In spite of small strength, this study arguments the fact that the
      angioplasty isn't sufficient to control the arterial hypertension in an
      atheromatous context, not allowing to slow the evolution of distal cortical
      lesions with however a stability of creatinine clearance.

PMID- 15506065
TI  - [Influence of moderate body weight excess on the nycthemeral pattern of blood
      pressure, renal function and sodium and water excretion in patients with
      essential hypertension].
AB  - Obesity is a risk factor for arterial hypertension. We studied the relationships
      between the body mass index (BMI) and the nycthemeral pattern of blood pressure
      (BP), renal function and sodium and water excretion (EX) in a group of 25
      moderately hypertensive untreated men (41 +/- 2 y, 80 +/- 3 kg). Subjects were
      given a high sodium diet (6 g NaCl added to their usual diet, daily EX=200 mmol).
      On the 7th day, BP was monitored during 24 h and urine collected in 2 fractions
      (day=D, 8:00-22:00 and night=N, 22:00-8:00). Subjects were a posteriori divided
      into 2 groups according to the median BMI (26 kg/m2): Group 1, n=12, BMI 23.2 +/-
      0.6 (mean +/- SEM) and Group 2, n=13, BMI 29.2 +/- 0.5 kg/m2. No difference was
      observed between the two groups for age, 24 h urine and sodium EX, or systolic
      and diastolic BP. However, heart rate was significantly higher during N in Group
      2 (66 +/- 2 vs 57 +/- 2 b/min, p=0.012). Na and water EX were significantly
      higher during D than during N in Group 1, but lower during D than during N in
      Group 2. Creatinine clearance was higher in Group 2 than in Group 1 especially
      during N (D+29%, p=0.013; N+49%, p<0.001). In Group 2, subjects concentrated
      their urine more than in Group 1, as evaluated from the urine/plasma creatinine
      ratio (+49%, p=0.019). This ratio was positively correlated to BMI during D
      (r=0.561, p=0.004) but not during N. These results show that the glomerular
      hyperfiltration associated with overweight is more intense at night and that
      moderately overweight hypertensives have a reduced sodium and water EX during the
      day and a compensatory larger EX at night. The reduced diurnal EX goes along with
      an increased urine concentration. The nocturnal rise in EX is concomittant with a
      rise in heart rate. Given the growing health problems linked to obesity and
      hypertension, these results open a new field for the understanding of the
      difficulty to excrete sodium in this condition.

PMID- 15506066
TI  - [Renal vascular lesions and the occurrence of hypertension in patients with IgA
      nephropathy].
AB  - Worse prognosis of IgA nephropathy (IgAN) is associated to hypertension, high
      proteinuria, glomerular and vascular sclerosis. A family story of hypertension
      (FHT) in relatives could be a strong predictor of the occurrence of hypertension
      (HT) in children. Renal vascular lesions (RVL) are often observed in normotensive
      patients with IgAN. In order to evaluate a possible association between FHT and
      LVR in patients with IgAN, we investigated two groups of 73 IgAN patients, sex
      (56 males and 17 females) and age matched, according to the presence or not of
      FHT. FHT was diagnosed if relatives and/or at least one child under 60 years of
      age had treatment for HT or systolic and diastolic BP over 140/90 mmHg at the
      time of the survey. Patients entering into the study were followed during an
      average period of 5 to 8 years. At the end of the study, all patients were
      explored for HT and renal function. Creatinine clearance (CrCl) was evaluated by
      Cockcroft and Gault formula and renal failure was defined as CrCl<60mL/min. The
      results were as follow: at the time of renal biopsy, RVL were observed in 73% of
      males with FHT vs 16% of males without FHT (p<0.0001) and 70.6% of females with
      FHT vs 29.4% of females without FHT (p<0.001); at the end of the study period, HT
      was significantly associated to FHT in 89.6% of patients group with FHT vs 22.6%
      of HT patients in the group without FHT (p<.0001). Renal failure was present in
      45.2% of patients with FHT vs 4.1% of patients without FHT (p<0.0001). These data
      suggest: VRL could be dependent of genetic factors; FHT should be an early
      predictor of VRL in patients with IgAN; FHT might be a risk factor for renal
      failure in patients with this renal disease.

PMID- 15506067
TI  - [Rilmenidine sympatholytic activity preserves mental and orthostatic sympathetic
      response and epinephrine secretion].
AB  - BACKGROUND: Heightened central sympathetic nervous outflow is common in essential
      hypertension, contributing to hypertension development and perhaps also to
      complications. Acute sympathetic nervous activation is a proven trigger for
      adverse cardiovascular events. Accordingly, antihypertensive drugs inhibiting
      sympathetic outflow represent a theoretically attractive therapeutic option.
      OBJECTIVES: To study the sympatholytic and blood pressure lowering activity of
      the imidazoline binding agent rilmenidine at rest and during reflex sympathetic
      activation. DESIGN AND METHODS: The HERA study (Hyperium Effect on the
      sympathetic Reflex activation and Adrenaline) is a randomised, double-blind, 6
      week cross-over trial, with a 1-week placebo run-in period, two 2-week active
      treatment intervals (rilmenidine 1 mg bid, placebo) and intervening one week
      placebo wash-out. In 15 hypertensive patients, noradrenaline and adrenaline
      plasma kinetics and intra-arterial blood pressure measurements were performed at
      rest, after mental stress (difficult mental arithmetic) and during head-up
      tilting, at the end of the 2-week dosing periods. RESULTS: The noradrenaline
      spillover rate, indicative of whole body sympathetic activity, was reduced 35% by
      rilmenidine at rest (p<0.01) and remained significantly lower during mental
      stress and tilting, although the increases in noradrenaline spillover with both
      stimuli were preserved. The effects on intraarterial blood pressure ran in
      parallel, a fall in supine resting pressure, but no reduction in BP rise during
      mental stress and a lack of fall in BP with tilting. On placebo, adrenaline
      secretion was 162 +/- 27 ng/min (mean, SE) at rest, increased by 77 +/- 42 ng/min
      with mental stress (p=0.019) and was unchanged with tilting. Rilmenidine left
      adrenaline secretion untouched under all conditions. CONCLUSIONS: This study
      confirms a sympatholytic effect of rilmenidine during supine rest but
      demonstrates that sympathetic responses during mental stress and tilting are
      preserved, the latter underlying a perhaps surprising absence of postural
      hypotension on the drug. The absence of suppression of reflexive sympathetic
      responses contrasts with the effects of rilmenidine in experimental animals, and
      emphasises the previously demonstrated unique importance in humans of suprabulbar
      noradrenergic neuronal projections from the brainstem, which are inhibited by
      imidazoline binding agents, in regulating tonic sympathetic activity in essential
      hypertension. Sympathetic nervous inhibition with rilmenidine contrasted with an
      absence of suppression of the secretion of adrenaline affirming that here, as
      elsewhere, sympathetic nervous and adrenal medullary function can be
      disconnected.

PMID- 15506068
TI  - [A comparison of the management of severe high blood pressure between 1999 and
      2003 in France].
AB  - AIM: To measure the change in blood-pressure control in two populations of
      patients with severe high blood pressure between 1999 and 2003. METHOD: The
      French National Healthcare Fund performed two observational, cross-sectional
      surveys on the medical management of high blood pressure, the first in 1999 and
      the second in 2003. Each survey enrolled patients aged between 20 and 80 years
      old who filed a first-time request for exemption from co-payments for this long
      term disorder. Study data was collected by the health fund's salaried physician
      advisors who directly examined the patients and from information gathered from
      each patient's attending physician. Adequate blood pressure control was defined
      according to the guidelines set out by the ANAES in 1997 and determined by
      calculating the average of the last three blood pressure figures recorded by the
      patient's attending physician (systolic [SBP] and diastolic [DBP] arterial blood
      pressures). RESULTS: 10,665 patients were enrolled in the 1999 survey and 2,584
      were enrolled in the 2003 survey. The average age was 63.1 +/- 0.2 years in 1999
      and 64.4 +/- 0.4 years in 2003. The proportion of diabetic patients in the two
      surveys remained stable: 27.5% +/- 1.0 in 1999 and 28.4% +/- 1.7 in 2003. Between
      1999 and 2003, the percentage of patient who were treated for
      hypercholesterolemia increased from 44.0% +/- 1.1 to 54.3% +/- 1.9. Between 1999
      and 2003, the proportion of patients who were considered well-controlled (SBP and
      DBP < 140/90 mmHg) or, if older than 60 years with isolated systolic high blood
      pressure (DBP < 90 mmHg and SBP < or = 160 mmHg) increased almost 5% points,
      going from 40.8% +/- 1.1 in 1999 to 45.5% +/- 1.9 in 2003. In diabetic patients,
      in whom the cut-off threshold is 130/85 mmHg, 6.7% +/- 1.1 were considered well
      controlled in 1999 while 5.4% +/- 1.7 were deemed well-controlled in 2003. The
      proportion of well-controlled patients in the sub-group of hypertensive patients
      with renal failure (cut-off thresholds: 125/75 mmHg) remained relatively stable
      between 1999 and 2003: 5.2% [2.5; 7.9] versus 2.8% [0.5; 8.6]. CONCLUSION: There
      was a significant increase in the proportion of well-controlled hypertensive
      patients between 1999 and 2003. This increase occurred at the same time as a
      number of initiatives (scientific societies, federal government as well as the
      National Health Fund) intended to sensitize physicians to the need to obtain
      adequate blood pressure control.

PMID- 15506069
TI  - [Evolution of circadian blood pressure and urinary albumin excretion according to
      the type of diabetes over a 10-year period].
AB  - The aim of the present study was to evaluate the circadian blood pressure and
      rinary albumin excretion (UAE) according to the type of diabetes over a 10-year
      period. PATIENTS AND METHODS: This study is based on 43 diabetic patients, 24
      type 1 and 19 type 2. Ambulatory blood pressure monitoring was used to assess
      blood pressure at the initial evaluation (A0) and about 10 years later (A10). UAE
      was also checked at 10 years interval and was <30 mg/day at A0. RESULTS: At A0,
      ABPM and UAE did not differ in a significant manner between type 1 and type 2
      diabetics. Type 2 diabetic patients were older than type 1 (59.7 +/- 15.4 vs 42.9
      +/- 12.9; p<0.0001) but the age of diabetes did not differ between the 2 groups.
      Between A0 and A10, there was an increase in 24 h SBP of type 1 and type 2
      diabetics (type 1: 114 +/- 10 vs 124 +/- 12 mmHg; p<0.01 and type 2: 113 +/- 19
      vs 135 +/- 13 mmHg; p<0.0001). 24 h DBP, as well as BP differences (day-night)
      did not differ between the 2 evaluations. At A10, 24 h SBP was higher in type 2
      than in type 1 (135 +/- 13 vs 124 +/- 12 mmHg; p<0.001) but differences between
      day and night BP were not significant. In type 1 diabetes, progression of SBP was
      not associated with an increase in UAE rate, while this rate increased in type 2
      betwwen A0 and A10 (9 +/- 7 vs 70 +/- 101 mg/24 h; p<0.01). AT A10, UAE was
      higher in type 2 than in type 1 diabetes (70 +/- 101 vs 14 +/- 31 mg/24 h;
      p<0.02). In type 2 diabetes, the progression of UAE was correlated with SBP at
      A10 (r=0.495; p<0.03). CONCLUSION: The increase in BP levels and in UAE rate
      differ between type 1 and type 2 diabetes and these differnces are not due to
      patients age, nor to modifications in BP curves. They are probably linked to a
      physiopathology which could be more complex in type 2 than in type 1 diabetes.

PMID- 15506070
TI  - [Recommendations for the diagnosis and management of cardic failure in the
      elderly subject].

PMID- 15506071
TI  - Gender and hormonal regulation of growth.
AB  - Puberty is the transitional period between childhood and adulthood when
      substantial growth, sexual maturation, and reproductive capacity is attained. The
      onset of puberty is triggered by the combined action of the somatotropic (GH-IGF
      I) and gonadotropic (GnRH-LH/FSH-sex steroid) hormone axes, the latter of which
      stimulates the former to produce the pubertal growth spurt. Studies of GH
      secretion in boys and girls, in Turner's syndrome, in hypogonadal girls, and in
      androgen-deficient boys have revealed estrogen-dependent mechanisms controlling
      GH production, age-dependent response to and control of GH, and gender-dependent
      differences in response to GH therapy. The interplay between the somatotropic and
      gonadotropic hormone axes during puberty has profound implications on the
      treatment of adolescent patients in need of hormone replacement therapy for
      growth deficiency or hypogonadism.

PMID- 15506072
TI  - Gender differences in height: an evolutionary perspective.
AB  - Homo sapiens (H. sapiens) exhibits growth characteristics not observed in other
      mammals, including other primates. Both male and female H. sapiens experience
      pubertal growth spurts and are not sexually dimorphic in adult stature. These
      unique growth characteristics must have evolved to benefit the reproductive
      success and survival of the species. The H. sapiens childhood is relatively
      protracted, and the pubertal growth spurt may be a compensatory measure to attain
      adult size in a relatively short time. Because reproductive patterns of H.
      sapiens have evolved away from a male-dominated social structure, large male size
      no longer confers a reproductive advantage. The relatively large female size of
      H. sapiens might have evolved to support the birth of offspring with ever
      increasing cranial characteristics. Growth in H. sapiens depends largely on GH
      dependent STAT5b regulation of IGF-I expression. STAT5b in other mammals
      contributes to growth in males only. Although speculative, the loss of sexual
      dimorphism in H. sapiens may reflect a progressive dependence on STAT5b to
      control growth.

PMID- 15506073
TI  - Growth hormone and estrogen: a clinician's approach.
AB  - Adult patients with growth hormone (GH) deficiency require long-term treatment
      with GH to support normal physiological functioning. For many female patients,
      endogenous estrogen levels have a considerable impact on the dosing requirements
      for GH. Estrogen appears to stimulate GH secretion by decreasing liver secretion
      of insulin-like growth factor-I (IGF-I), resulting in stimulation of the
      pituitary to synthesize and secrete GH. Oral estrogen results in a higher
      concentration of liver estrogen than transdermal administration of estrogen. The
      appropriate dose of GH needs to be determined for each patient based on his or
      her age, sex, concomitant estrogen therapy, IGF-I level, and short- and long-term
      response to therapy. Clinical endocrinologists are in the best position to put
      all these variables into a successful therapeutic scenario.

PMID- 15506074
TI  - Induction of puberty in hypogonadal children.
AB  - Puberty is the transitional period between childhood and adulthood when physical,
      sexual, and psychosocial maturation occurs. The onset of puberty is controlled by
      the gonadotropin-releasing hormone (GnRH) neuron and is triggered when inhibition
      of the neuron is lifted. Subsequently, GnRH induces secretion of other hormones,
      follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which in turn
      stimulate the gonads. Concurrently, increases in estrogen levels in both boys and
      girls stimulate growth hormone (GH) and insulin-like growth factor-I (IGF-I)
      secretion, which are responsible for the pubertal growth spurt. In hypogonadal
      children, however, hypothalamic/pituitary defects or gonadal diseases preclude
      the production of these hormones, preventing the onset of puberty. Hormone
      replacement therapy with either estrogen or testosterone is a viable treatment
      option for hypogonadal children. These should be administered with consideration
      of sexual maturation rates, statural and bone growth rates, and occurrence of
      adverse effects. The merits and disadvantages of various hormone replacement
      therapies for girls and for boys are discussed.

PMID- 15506075
TI  - The hypothalamic path to obesity.
AB  - Obesity is a growing public health concern, affecting an estimated 11% of
      children in Western society. The impact of obesity-related morbidity and
      mortality on society is significant, with both genetic and environmental factors
      contributing to its development. In most individuals, food intake and energy
      expenditure are tightly regulated by a feedback system comprising a number of
      hormonal and central nervous system pathways. Leptin released from adipocytes
      acts on hypothalamic neurons to release proopiomelanocortin (POMC), leading to a
      cascade of neuronal and hormonal events that inhibit feeding behavior. Specific
      gene mutations in the leptin/POMC pathways account for only 5% of all cases of
      obesity, and most cases of familial or idiopathic obesity are polygenic in
      origin. Although further research to identify specific genetic causes of obesity
      may lead to more tailored therapies, significant changes in societal and
      individual behavior are needed to stop the obesity epidemic from progressing.

PMID- 15506076
TI  - Growth hormone therapy for Prader-Willi syndrome: a critical appraisal.
AB  - Prader-Willi syndrome (PWS) is characterized by hypothalamic dysfunction
      resulting in obesity, hypotonia, hypogonadism, and behavioral abnormalities.
      Clinical features of PWS resemble those of GH deficiency (decreased total lean
      body mass, IGF-I levels, and poor linear growth). Marked reductions in muscle
      mass are associated with diminished strength, physical function, and energy
      expenditure. Lifelong morbidities of PWS include osteoporosis, type 2 diabetes
      mellitus, respiratory disorders, and cardiorespiratory failure related to obesity
      and hypotonia. Recent studies show that GH therapy improves linear growth, final
      height, physical strength, and agility in patients with PWS. Some effects of GH
      therapy wane with time, however, and strategies for treating adults with PWS
      remain uncertain. In addition, deaths in markedly obese, GH-treated children with
      PWS have been reported, and a possible contribution of GH to these events has not
      yet been definitively excluded. Consequently, critical evaluation should continue
      of the long-term benefits, risks, and costs of GH therapy for patients with PWS.

PMID- 15506077
TI  - Adult growth hormone deficiency: current trends in diagnosis and dosing.
AB  - Only approximately 20% of adults with GH deficiency (GHD) have a history of
      childhood-onset GHD; the remainder acquire GHD in adult life, usually through
      acquired damage to the pituitary-hypothalamic region. Diagnosis of GHD in adults
      is more difficult than in children and is made first from the clinical context,
      reinforced by signs and symptoms, and then confirmed by biochemical testing. The
      signs and symptoms, however, including altered body composition, reduced energy,
      and mild depression, are too common to have diagnostic value without a suggestive
      clinical context. Furthermore, biochemical tests for GH or IGF-I levels are
      imperfect, characterized by significant false-positive and -negative rates. GH
      dosing in adults has shifted to an individualized dose-titration approach, in
      which treatment is begun at a fixed dose and then titrated upward until IGF-I
      levels normalize, significant side effects develop, or beneficial effects
      plateau. Generally, women require higher GH doses than do men. Reflecting age
      related differences in normal GH secretion, GH doses may be higher in young
      adults and lower in older patients.

PMID- 15506078
TI  - GH, IGF-I, and growth.
AB  - Recent studies have confirmed the importance of the growth hormone (GH)-insulin
      like growth factor-I (IGF-I) axis as the major determinant of whole body growth
      in animals and humans and have highlighted the significance of IGF-I to human
      growth. Pharmacological studies in rodents and therapeutic studies in humans
      demonstrate that recombinant human (rh)IGF-I can induce a significant statural
      growth response. Mouse gene knockout studies have shown that IGF-I, rather than
      GH, is the major hormone controlling whole body growth. The relative importance
      of endocrine versus local IGF-I remains unresolved. In children who are GH- and
      IGF-I-deficient, treatment with GH stimulates a robust growth response. In
      children who are IGF-I-deficient but GH-sufficient, rhIGF-I might also be a
      useful treatment. Furthermore, pharmacological and genetic studies in animals
      show effects requiring the combined presence of GH and IGF-I, suggesting that
      rhGH and rhIGF-I together might be the optimal treatment for some children with
      short stature.

PMID- 15506079
TI  - Bone mineral density in chronic renal insufficiency and end-stage renal disease:
      how to interpret the scans.
AB  - Bone disorders are common in renal disease and stem largely from deregulation of
      serum levels of calcium and phosphorus. Accurate methods of assessment are
      required to monitor bone mineral content and density changes in patients with
      renal disease, but current methods are complicated. Interpretation of dual-energy
      X-ray absorptiometry (DXA) measurements in children is difficult, because the
      areal component that is measured does not adequately reflect bone that is
      constantly growing. In adults with renal disease, the inability of DXA
      measurements to distinguish between cortical and cancellous bone is problematic.
      The recent advent of quantitative computerized tomography (QCT), however, does
      permit resolution of cancellous and cortical bone. In children with renal
      osteodystrophy, QCT could show reduced cortical bone density and distinguish
      differences in total bone density between patients with high-turnover bone
      disease and those with adynamic bone disease. The strengths and limitations of
      these imaging techniques are discussed extensively.

PMID- 15506080
TI  - Image analysis and coummunity monitoring on coniferous forest dynamics in
      Changbai Mountain.
AB  - The structure and dynamics of coniferous forests in Changbai Mountain were
      studied at different spatial scales, including ground survey of permanent plots
      and analysis of multitemporal satellite images. Plot-scale examinations showed
      that the mortality rate was 7% - 9%, and the recruitment rate was 18% - 20% per
      10 years. Species composition changed over time. Picea jezoensis var.
      microsperma, Abies nephrolepis and Betula ermanii presented a self-maintaining
      capability, because they could regenerate under canopy. Larix olgensis was a
      pioneer species and could regenerate only in open land or gaps. This species
      played an important role by providing conditions for the regeneration of spruce
      and fir. The tree density in the mature forest was 1 000 stems x hm(-2) for trees
      bigger than 3 cm in diameter, which showed no significant variations among
      different stands. Landsat TM images were used for detecting the cover changes
      from 1984 to 1997. Large scales of wind throw were detected by this approach.
      Based on t he analysis of radiance changes at the landscape scale, the pixel
      number of the disturbed area was similar to that of the succeeding stands,
      suggesting that the forest was in a state of equilibrium. Fine gaps, however,
      were difficult to identify with the TM data because of its coarse resolution. The
      mosaic structure ofthe subalpine vegetation was characterized by scattered larch
      patches. At the landscape level, the vegetation was in a stable stage.

PMID- 15506081
TI  - [Effects of site condition on litterfall and related nutrient return in Pinus
      luchuensis plantations].
AB  - Over three years study on the dynamics of litterfall and related nutrient return
      in Pinus luchuensis plantations at different sites of northern Okinawa Island,
      Japan showed that the annual litterfall biomass ranged from 6.54 to 8.05 Mg x hm(
      2) x yr(-1), with a peak from June to July. Typhoons had a strong influence on
      the timing and mass of litterfall. There were significant differences in nutrient
      concentrations among the different components of litterfall. The annual total
      nutrient input from litterfall ranged from 113.4 to 154.6 kg x hm(-2) x yr(-1),
      of which, N input was the greatest and contributed 42.2% of the total. The
      nutrient input was in order of N > Ca > K > Mg > Na > P. Due to the significantly
      different site conditions, there were significant differences in annual
      litterfall mass and related nutrient inputs between the two sampling stands. The
      annual mean litterfall mass of the sampling stand P1 on the lower slope reached
      8.05 Mg x hm(-2) x yr(-1), which was 23.1% greater than that of P2 on the upper
      slope. The annual mean nutrient inputs were N 66.04, P 1.63, K 17.42, Ca 48.31,
      Mg 14.65 and Na 6.57 kg x hm(-2) x yr(-1), and were 39.7%, 48.8%, 39.4%, 32.9%,
      24.8% and 49.3% higher in P1 than in P2, respectively. The nutrient use
      efficiency in litter production was higher in P2 (e.g., N 138, P 5945 and K 523)
      than in P1 (e.g., N 122, P 4934 and K 462), which should be attributed to the
      relatively lower fertility of soil in P2. The results from the study suggested
      that Pinus luchuensis plantation in Okinawa was a high efficiency system.

PMID- 15506082
TI  - [Gaps and their natural disturbance characteristics in mid-subtropical evergreen
      broad-leaved forest in Wanmulin].
AB  - Through field investigation on 96 gaps in some permanent plots of mid-subtropical
      evergreen broad-leaved forest in Wanmulin Natural Reserve of Fujian Province,
      this paper dealt with the gap characteristics and their natural disturbance. The
      results showed that the area percentage of expanded gap (EG) and canopy gap (CG)
      in the forest landscape was 50.86% and 16.66%, and the natural disturbance
      frequency for EG and CG was 0.85% x yr(-1) and 0.28% x yr(-1), respectively. The
      return interval of canopy gaps was about 357 years. The most popular manner of
      gap formation in the forest was stem breakage (58.04% of the total), and the
      second was uprooting (33.48%). Most gaps were formed by two trees, averaging 2.33
      trees per gap. The size of most expanded gaps was in the range of 100 - 300m2,
      the gaps of 200 - 300m2 occupied the biggest percentage in area, and those of 100
      - 200m2 occupied the biggest percentage in number. The size of most canopy gaps
      was under 100m2, and the gaps of < 50m2 had the biggest percentage in area and
      number. The diameter at breast height of most gap makers was 20 - 30cm.

PMID- 15506083
TI  - [Relationships between light and physiological characters of five climbing
      plants].
AB  - Studies on the photosynthetic and respiratory rates, light utilization
      efficiencies and light compensations of five climbing plants showed that the
      diurnal variations of photosynthetic rates presented double peak, the first peak
      was between 10:00 to 12:00, and the second was between 14:00 to 16:00. The
      phenomenon of "noon break" was obvious. The diurnal variations of respiration
      rates also presented double peak, the first peak was between 11:00 to 13:00, and
      the second was between 14:00 to 17:00. The light compensation point of Hedera
      nepatensis, H. helix, Parthenocissus tricuspidata, P. quinuefolia and Wisteria
      sinensis was 5.73, 5.07, 9.96, 6.40 and 18.93 micromol x m(-2) x s(-1),
      respectively, and the light utilization efficiency of W. sinensis was higher
      under strong light, P. quinuefolia was the second, but that of H. helix was
      higher under weak light. The results showed that Wisteria sinensis was a typical
      heliophytic plant, Parthenocissus tricuspidata and P. quinuefolia were neuter
      plants, and Hedera nepalensis and H. helix were typical sciophytic plants.

PMID- 15506084
TI  - [Monthly changes in caloric values of five shrubby Palmae species leaves].
AB  - Studies on the monthly changes in the ash contents and caloric values of 5
      shrubby Palmae species (Chamaerops humilis, Rhapis gracilis, Sabal minor,
      Chamaedorea cataractarum, Chamaedorea brachypoda) leaves showed that annual
      average ash content of the five shrubby species was 4.87% +/- 1.37% for
      Chamaerops humilis, 8.33% +/- 0.89% for Rhapis gracilis, 7.85% +/- 2.64% for
      Sabal minor, 9.20% +/- 1.35% for Chamaedorea cataractarum, and 12.42% +/- 1.78%
      for Chamaedorea brachypoda. The monthly changes of gross caloric value were
      different for Chamaerops humilis, Rhapis gracilis and Sabal minor, but similar to
      each other for Chamaedorea cataractarum and Chamaedorea brachypoda, and the
      annual average gross caloric value of the five shrubby species was 20.50 +/- 0.32
      kJ x g(-1) for Chamaerops humilis, 20.04 +/- 0.50 kJ x g(-1) for Rhapis gracilis,
      20.21 +/- 0.68 kJ x g(-1) for Sabal minor, 20.52 +/- 0.48 kJ x g(-1) for
      Chamaedorea cataractarum and 18.90 +/- 0.47 kJ x g(-1) for Chamaedorea
      brachypoda. The gross caloric values were correlated remarkably with ash contents
      for Chamaedorea cataractarum and Sabal minor (P < 0.05), but there was no
      significant correlation between gross caloric values and ash contents for other
      three species (P > 0.05). Rhapis gracilis and Sabal minor, and Chamaedorea
      cataractarum and Chamaedorea brachypoda had similar monthly changes in ash free
      caloric values, respectively. The average ash free caloric value of the five
      shrubby species was 21.55 +/- 0.53 kJ x g(-1) for Chamaerops humilis, 21.87 +/-
      0.46 kJ x g(-1) for Rhapis gracilis, 21.84 +/- 0.53 kJ x g(-1) for Sabal minor,
      22.60 +/- 0.81 kJ x g(-1) for Chamaedorea cataractarum, and 21.59 +/- 0.63 kJ x
      g(-1) for Chamaedorea brachypoda. Chamaedorea cataractarum had a higher ash free
      caloric value than other four species (P < 0.05), and the ash free caloric values
      of Chamaerops humilis, Rhapis gracilis, Sabal minor and Chamaedorea brachypoda
      were similar, the differences being not significant by t test (P > 0.05).

PMID- 15506085
TI  - [Genetic diversity of rare and endangered plant Magnolia amoena].
AB  - The genetic variations within and between eleven natural populations and one
      cultured population of Magnolia amoena from different distribution regions were
      investigated at the DNA level by employing RAPD. Out of 40 random primers,
      fourteen random primers were screened which could generate highly reproducible
      and clear RAPD fragments for further population analysis. With these primers, a
      total of 94 discernible DNA fragments were obtained and 23 (24.4%) were
      polymorphic, which indicated that low levels of genetic variation existed in the
      investigated populations. In addition, UPGMA map were made according to the
      genetic similarity and distance of the twelve populations calculated in this
      article. The result showed that the genetic diversity between individuals within
      population was lower than that between populations. The individual genetic
      differentiation might be relation to their geographic distribution. The low total
      genetic diversity of Magnolia amoena was one reason for its endangerment.

PMID- 15506086
TI  - [Effects of meteorological factors and mineral elements on the content of
      resveratrol in Polygonum cuspidatum rootstalk].
AB  - By determining monthly the content of resveratrol and eight mineral elements (Ca,
      Cu, Fe, K, Mg, Na, Zn, Mn) in the rootstalk of Polygonum cuspidatum, by
      considering the dynamic meteorological factors and by analyzing the principal
      components, we are investigating the dynamic relationship laws among mineral
      elements, meteorological factors and the content of resveratrol in Polygonum
      cuspidatum rootstalk in varied seasons. The results indicated that the
      correlation coefficient between Cu and Fe; between Mg and K; between Mg and Zn;
      between K and Zn; between Ca and average sunlight hours per month are 0.812,
      0.871, 0.793, 0.729, 0.602. Their correlation is markedly in the positive 0.01
      levels. The correlation coefficient between Cu and average air temperature in a
      month; between Mn and average air temperature in a month; between Fe and K are 
      0.738, -0.712, -0.766. Their correlation is markedly in negative 0.01 levels. The
      correlation between Cu and the content of resveratrol is markedly in negative
      0.05 levels. Of the five principal factors affecting the content of resveratrol,
      two were found to be principal: "mineral element factors of promoting enzyme
      reacts" and "the meteorological factors of high temperature and strong shines".
      The percentage results of these two principal are 33.539% and 33.358%, making a
      total of 68.897%. The two factors above are also the main reasons for the
      variation of Polygonum cuspidatum resveratrol. A regression equation was set up
      through correlation and regression analysis between the changing content of
      resveratrol and the principal component.

PMID- 15506087
TI  - [Soil water characteristics in Picea crassifolia forestry lands in Qilian
      Mountains].
AB  - The study of soil water content and its main affecting factors in Picea
      crassifolia forestry lands in Qilian Mountains showed that the Picea crassifolia
      forestry lands were characterized by lower soil bulk weight and higher soil water
      infiltration rate, and the vertical distribution of soil water was apparently
      affected by precipitation. The soil bulk weight of shrub-Picea crassifolia
      forestry land, moss-Picea crassifolia forestry land and meadow land was 0.522,
      0.641 and 0.874 g x cm(-3), initial water infiltration rate was 6.0, 21.0 and 2.5
      mm x min(-1), and stable infiltration rate was 3.98, 11.2 and 0.5 mm x min(-1),
      respectively. The soil of moss-Picea crassifolia land in 100 cm depth could be
      partitioned into 4 layers, i.e., active layer (0 - 30 cm), regulation layer (30 -
      60 cm), transmission layer (60 - 80 cm) and accumulation layer (below 80 cm), and
      the amount of stored water in each layer was 3.30, 3.17, 2.80 and 2.83 mm x cm(
      1), respectively. The soil of shrub-Picea crassifolia land could be partitioned
      into 3 layers, i.e., stable layer (0 - 30 cm), active layer (30 - 60 cm) and
      transmission layer (below 60 cm), and the amount of stored water in each layer
      was 3.98, 3.65 and 3.48 mm x cm(-1), respectively. The seasonal variance of soil
      water content in Picea crassifolia forestry lands was strongly affected by
      precipitation. The water holding capacity of shrub-Picea crassifolia forestry
      land was higher and the water transmission capability was lower than that of Moss
      Picea crassifolia forestry land.

PMID- 15506088
TI  - [Comprehensive evaluation and selection of urban eco-engineering virescent trees
      in Shenyang City].
AB  - Urban virescence eco-engineering is the core of urban eco-environmental
      construction, which can promote urban sustainable development. In urban
      virescence eco-engineering, the comprehensive evaluation of ecological adapt
      ability and ecological effect of urban plants is the scientific basis of rational
      application and selection of urban garden plants. The ecological effect and
      integrative functions of urban virescence eco-engineering depend upon the
      selection and layout of garden plants. Using the methods of garden expert
      consultation and evaluation, this paper established systematically integrative
      evaluation and application indices of virescence plants in Shenyang City, from
      the aspects of ecological adaptability, ecological effect, beautification effect,
      resistance to plant diseases and insect pests, anti-pollution and economic
      results. According to garden experts evaluation and location of Shenyang, 200
      sorts of virescence trees were evaluated and classified on the basis of the
      comprehensive evaluation system of virescence trees, and using cold resistance,
      drought resistance, barren resistance, plant diseases and insect pests
      resistance, anti-pollution, ornamental quality and ecological effects as the
      indexes. The results showed that the number of first rank trees was 58, the
      second was 93, methods of third was 38, and the fourth was 11, ranked by
      integrative performance.

PMID- 15506089
TI  - [Vegetation diversity of wild Chinese alligator (Alligator sinensis) habitats].
AB  - In June and July of 2003, a field survey on the vegetation of 22 Chinese
      alligator habitats distributed in Nanling county, Jingxian county, Guangde
      county, Langxi county and Xuancheng city of Anhui province was conducted, and the
      plant species of the habitats were recorded and analyzed. The results showed that
      the vegetation of the whole habitats was secondary, and there were 294 species
      vascular plants, belonging to 92 families. Pteioblastus amarus shrubbery could be
      found in all sites, and part differences of the vegetation consisted in different
      habitats. The relationship between Chinese alligator and habitat vegetation was
      also analyzed. All of these could offer some basic botanical data for the further
      protection of the Chinese alligator.

PMID- 15506090
TI  - [On the causes of mite pest outbreaks in mono- and poly-cultured moso bamboo
      forests].
AB  - In this paper, the damage of phytophagous mites Schizotetranychus nanjingensis Ma
      & Yuan, Aponychus corpuzae Rimando and Aculus bambusae Kuang to moso bamboo
      (Phyllostaychs pubescens) was examined for ten pairs of mono- and poly-cultured
      forests at six locations in Fujian, China. The results showed that the mite
      damage in mono-cultured forests (35%) was twice as high as that in poly-cultured
      forests (17.5% < the injury level of 20%), and the difference was significant by
      t-test. The total pest mites in the mono-cultured forests at six locations in
      Fujian were 289.29% as high as those in the poly-cultured stands. Typhlodromus
      bambusae, a nature enemy in the poly-cultured forests at five locations in
      Fujian, was 262.5% as high as that in the mono-cultured forests. The proportion
      of pest mite and nature enemy in the mono-cultured forests was 1:118, but was
      1:13 in the poly-cultured forests. The change of bamboo cultivation (mono
      culture, crowding of bamboo plants, and removal of underfloor plants) might be
      the major cause of mite pest outbreaks in moso bamboo forests.

PMID- 15506091
TI  - [Krigle estimation and its simulated sampling of Chilo suppressalis population
      density].
AB  - In order to draw up a rational sampling plan for the larvae population of Chilo
      suppressalis, an original population and its two derivative populations, random
      population and sequence population, were sampled and compared with random
      sampling, gap-range-random sampling, and a new systematic sampling integrated
      Krigle interpolation and random original position. As for the original population
      whose distribution was up to aggregative and dependence range in line direction
      was 115 cm (6.9 units), gap-range-random sampling in line direction was more
      precise than random sampling. Distinguishing the population pattern correctly is
      the key to get a better precision. Gap-range-random sampling and random sampling
      are fit for aggregated population and random population, respectively, but both
      of them are difficult to apply in practice. Therefore, a new systematic sampling
      named as Krigle sample (n = 441) was developed to estimate the density of partial
      sample (partial estimation, n = 441) and population (overall estimation, N =
      1500). As for original population, the estimated precision of Krigle sample to
      partial sample and population was better than that of investigation sample. With
      the increase of the aggregation intensity of population, Krigel sample was more
      effective than investigation sample in both partial estimation and overall
      estimation in the appropriate sampling gap according to the dependence range.

PMID- 15506092
TI  - [Bioactivity of Myoporum bontioides extracts to Plutella xylostella].
AB  - The bioactivity of Myoporum bontioides extracts to Plutella xylostella was
      studied with IIPC as evaluated index. The results showed that petroleum ether and
      chloroform extracts had a higher activity than ethyl acetate and alcohol
      extracts. At 0.01 gDW x ml(-1), the ODR of petroleum ether and chloroform
      extracts was 84.69% and 79.90%, and 76.47% and 45.70% after treated 1d and 3d,
      while the IIPC was 0.1565 and 0.2055, respectively. Provided with a higher
      concentration of 0.05 gDW x ml(-1), the ODR was 88.52% and 72.25%, and 87.33%,
      58.37%, while the IIPC was 0.1125 and 0.2620, respectively. From the chloroform
      extract of Myopdrum Bontioides, three flavonoids, 2, 3-dihydro-5, 7-dihydroxy-2
      phenyl-4H-1-Benzopyran-4-one (I), 3, 5, 7-trihydroxy-2-phenyl-4H-1-Benzopyran-4
      one (II) and 5, 7-dihydroxy-3-methoxy-2-(4-methoxyphenyl)-4H-1-Benzopyran-4-one
      (III), were isolated, and their structure were identified based on the analyses
      of physical and spectrum data. Among these compounds, (II) had a better
      bioactivity to Plutella xylostella.

PMID- 15506093
TI  - [Interaction between chlopyrifos and microorganisms in soils].
AB  - The experimental results showed that in sterilized soils, the degradation rate of
      50 mg x kg(-1), 500 mg x kg(-1) and 5,000 g x kg(-1) chlopyrifos was very slow
      (only 20% after 60 d), and in soils which previously treated with chlopyrifos,
      the degradation rate of 50 mg x kg(-1), 500 mg x kg(-1) and 5,000 mg x kg(-1)
      chlopyrifos was 100%, 90% and 80%, respectively. However, in un-sterilized and
      untreated soils, the degradation rate was at the medium of the rates mentioned
      above, indicating that soil microorganisms played an important role in
      chlopyrifos degradation, and using chlopyrifos could induce the chlopyrifos
      degrading ability of soil microorganisms. Compared to the soils untreated with
      chlopyrifos, the soils treated with 50 mg x kg(-1) and 500 mg x kg(-1)
      chlopyrifos had somewhat increased bacteria and fungi during a short period of
      treatment, which recovered to normal level after 60 days. But, when treated with
      5,000 mg x kg(-1) chlopyrifos, the bacteria and fungi were inhibited, and
      couldn't recover after 60 days. Under the same treatment condition, the number of
      bacteria and fungi was not different between soils previously treated and
      untreated with chlopyrifos, which indicated that enhanced degradation of
      chlopyrifos was not decided by the numbers of bacteria and fungi, but by their
      ability of enhanced degradation.

PMID- 15506094
TI  - [Effect of tillage system on soil animal, microorganism and enzyme activity in
      paddy field].
AB  - A long-term experiment showed that under ridge-no-tillage, the amount of soil
      animal in 0 - 20 cm layer was 14700 ind. x m(-2), while under no-tillage and
      fallow in winter, paddy-upland rotation, and conventional tillage, it was 10450,
      7950 and 6275 ind. x m(-2), respectively. Soil microbial biomass and microbial
      biomass N were more in spring and autumn, and less in summer. Soil enzyme
      activity was higher in surface soil layer and lower in bottom soil layer. The
      amount of soil animal, microbial biomass and microbial biomass N and soil enzyme
      activity was in order of ridge-no-tillage > paddy-upland rotation > no-tillage
      and fallow in winter > conventional tillage. The results also indicated that
      ridge-no-tillage was advantageous to improve soil ecological environment and soil
      fertility in paddy field.

PMID- 15506095
TI  - [Dynamics of three kinds of nitrogen in surface water of rice field with an
      independent irrigation system].
AB  - Studies on the dynamics of NH4+, NO3- and TN concentrations in the surface water
      of paddy field with an independent irrigation system showed that the
      concentration of NH4+ and TN in surface water was increased to the maximum after
      1day of each urea application, and then decreased rapidly with time. The ratio of
      NH4+/TN, NO3-/TN and (NH4+ + NO3-)/TN was increased firstly, and then decreased.
      NH4+ and TN could be used as the main indexes for the water pollution of the
      paddy field, and NO3- used as the assistant one. There existed a positive
      relation between the concentration of these three kinds of nitrogen and N
      application amount. Nine days after urea application was the key time to prevent
      the gross loss of the three kinds of nitrogen in the water surface of the paddy
      field. The simulation expressions of NH4+ and TN with time factor could be
      exponential, logarithmic, power or binomial, while NO3- had no appropriate
      expression. The simulation with factors of time and N application amount showed
      that the simulation expressions of NH4+ and TN were the same.

PMID- 15506096
TI  - [Extensive grazing and designed feeding with supplemented legume forages on
      natural grassland].
AB  - Livestock needs to be fully stuffed and fed well. Eating-well can compensate
      eating-full, and can rapidly increase the body weight of livestock, shorten its
      feeding period, enhance its production, and protect natural grassland from
      overgrazing. A designed feeding based on extensive grazing on natural grassland
      by supplementing rich crude protein-contained forage might be a new trend for
      optimizing the animal husbandry on grassland. Adding 20% legume forages to the
      diets for wethers could make the live body weight get a 40%-65% increase,
      achieving 52-61 kg in October extending to December. Forage production, animal
      nutrition and animal production were the three relatively primary factors for
      grassland management while focusing on grazing. Some terms such as eating-well,
      eating-well degree, eating-full, eating-full degree, extensive grazing and
      designed feeding were also defined respectively in this paper.

PMID- 15506097
TI  - [Influence of male surgical sterilization on social behavior of Brandt's vole].
AB  - Using the method of surgical sterilization, this paper studied the influence of
      sterilized male on the social behavior of Brandt's vole. The results showed that
      there was no significant difference in the frequency of amicable and agnostic
      behaviors between male surgical sterilization group and control, and between
      intact and sterilized males in the same group. It could be concluded that male
      surgical sterilization had no influence on the social behavior of Brandt's vole.

PMID- 15506098
TI  - [Dynamics of ecological landscape pattern and its affecting factors in desert
      oasis in Fukang, Xinjiang].
AB  - The spatial pattern of ecological landscape during land utilization in Fukang is
      heavily influenced by natural difference and the scale of water and land resource
      development. Analyses on the spatial pattern based on different zones and indexes
      showed that from 1987 to 1998, the change of the spatial pattern of ecological
      landscape during land utilization in Fukang was mainly the increase of plantation
      area in pluvial fan and the decrease in alluvial plain. The case was on the
      contrary about badlands. The acreage of woodland decreased in lower mountains,
      uplands and alluvial plain, but no variety in alluvial plain. The acreage of
      grassland increased in lower mountains and uplands, while decreased in other
      fields. The acreage of town increased in each sample field, while that of water
      area remained uncharged. The landscape diversity and evenness was descending, the
      dominance was ascending in lower mountains and in pluvial fan, while it was
      reverse in alluvial plain. Accessorial fragmentation showed the increasing
      influence of human beings. The change of the spatial pattern of ecological
      landscape in Fukang focused on the acreage alteration of plantation and badlands
      in pluvial fan and alluvial plain. The key factor was the dynamic variation of
      water-salt in water and soil resource utilization. Terrain and land utilization
      were the key factors affecting water table, and the continuous changes of the
      water table worked on the spatial distribution of soil water-salt.

PMID- 15506099
TI  - [Dynamic modeling of potato phenological development].
AB  - By means of systematic demonstration, this study found the mathematical
      relationship among several temperature driven nonlinear models for crop growth,
      and amended the limitation of the past nonlinear model in biological usage and
      the improved model with more general definition. Integrated with four years'
      field experimental data and Gauss function based temperature effectiveness model
      submitted in this study, the phenological development model for potato crop was
      established under different ecological conditions. The phenological development
      model explained the digital contribution of soil temperature increment on potato
      growth, and verified by the experimental data from different years and different
      conditions. There were strict co-relationships between modeling data and
      experimental data.

PMID- 15506100
TI  - [Growth and photosynthetic characteristics of field-grown Coffea arabica under
      different watering and fertilization managements].
AB  - Straw mulching and drip irrigation have been widely used for coffee production.
      In order to know if these techniques are suitable in Yunnan, five-year-old coffee
      plants were separated into 8 groups to grow in the field under 2 fertilization
      rates (low and high) and 4 watering regimes: dry straw mulching (M), drip
      irrigation (I), drip irrigation + straw mulching (MI) and control treatment (CK),
      and the effects of various watering and fertilization treatments on the growth
      and photosynthetic characteristics of Coffea arabica with the density of 4500
      individuals per hectare were measured. The results showed that during one year's
      growth period, the coffee plants had two growth peaks, one was in May when the
      rainy season just begun, and the another was in August to September, the middle
      of rainy season. Higher fertilization promoted the relative height and length
      growth rates of the branches, but watering treatments hadn't significant effects
      on them. In dry season, watering significantly promoted the Pn, gs, Tr and WUE,
      while water status had no significant influence on the internal fluorescence
      features of PSII. In wet season, high-fertilized plants had a higher leaf
      nitrogen content and Pn than low-fertilized plants, and Pn was positively
      correlated with leaf nitrogen content. In both seasons, higher fertilization
      increased the WUE regardless of the watering treatments. At the same time, the
      high-fertilization treatment significantly alleviated diurnal photoinhibition,
      companying with a higher energy utilization through photochemistry and a higher
      energy dissipation through xanthophyll cycle, which appears that high-fertilized
      coffee plants have the mechanism to acclimate to strong light environment. All
      the results indicated that wet season is the optimum time for the photosynthesis
      and growth of C. arabica, and C. arabica needs a high fertilization investment
      and fine watering managements during its whole growth period. Among the three man
      made watering treatments, MI was the best, M and I had the nearly same effects
      but the former was more practical than the latter.

PMID- 15506101
TI  - [Desiccation and nitrate accumulation of apple orchard soil on the Weibei
      dryland].
AB  - The study of apple orchard soil on the Weibei dryland showed that high input and
      high yield not only resulted in soil desiccation, but also induced nitrate
      accumulation in the soil profile. Generally, the soil layers with accumulated
      nitrate located in 40 - 260 cm depths, and the maximum nitrate content was 403.4
      mg x kg(-1). Owing to the continuous application of nitrogen fertilizer, the
      accumulated nitrate could hardly be reused in the future, which might lead to
      environmental pollution. Because the soil storage water could not adjust the
      water utilization of apple trees, the yield of orchard was affected by
      precipitation. Therefore, the nitrogen application rate should be reduced, and
      actions should be taken to improve soil moisture in apple orchard.

PMID- 15506102
TI  - [Response of rice grain quality traits to free-air CO2 enrichment].
AB  - The study showed that under field condition, when the CO2 concentration was
      elevated 200 micromol x mol(-1) above control, the average brown rice rate of
      japonica variety Wuxiangjing 14 was 1.4% higher, while lead milled rice rate was
      12.3% lower than control. The brown rice rate increased at lower nitrogen supply
      level (LN), while lead milled rice rate increased at higher nitrogen supply level
      (HN). The percentage of chalky grain was 11.9% higher, and chalkiness degree was
      2.8% higher than control, but no obvious difference was found in chalkiness area
      between the FACE and the control. The chalkiness area, percentage of chalky grain
      and chalkiness degree decreased at HN plus higher phosphorus supply level (HP).
      The gelatinization temperature was elevated 0.52 degrees C, gel consistency
      increased, while amylose content was not statistically significant. The amylose
      content decreased at HN plus HP, while gel consistency and gelatinization
      temperature decreased at LN plus HP and at LN, respectively. The protein content
      was decreased 0.6% under FACE treatment and at LN plus lower phosphorus supply
      level.

PMID- 15506103
TI  - [Changes of polyamines level in Glycine soja and Glycine max seedlings under NaCl
      stress].
AB  - With internationally common-used Glycine max (the salt-tolerant Lee68) and
      Glycine soja (the salt-sensitive N23232) as reference, this paper studied the
      polyamines (PAs) contents and polyamine oxidase (PAO) activities in the highly
      salt-tolerant BB52 (Glycine soja) seedlings, which showed that under 150mmol x L(
      1) NaCl stress for 2d, the decrease of Put and Spd contents was more significant,
      but that of Spd content was less significant in roots of BB52 than in those of
      Lee68 and N23232. For leaves, the decrease of Put and increase of Spd contents
      were markedly observed in BB52. The ascent of (Spm + Spd)/Put ratios and descent
      of Put/PAs ratios showed a positive relation to their salt tolerance. The PAO
      activity in roots and leaves was all increased, and most obvious in N23232. The
      relationship between PAs levels in BB52 and its salt tolerance was also
      discussed.

PMID- 15506104
TI  - [Effect of fertilization on cucumber growth and soil biological characteristics
      in sunlight greenhouse].
AB  - This paper studied the effect of fertilization on cucumber growth and yield, soil
      microbial biomass and soil enzyme activities in sunlight greenhouse in Loess
      Plateau. The results indicated that the growth and yield of cucumber were
      increased with application of manure and methane. Foliage application reduced the
      application rate of NP and manure. Fertilization had an obvious effect on the
      biological characteristics of soil in sunlight greenhouse. The number of bacteria
      was increased by manure and foliage fertilization, and that of fungi was
      increased by NP and methane fertilization but decreased by manure fertilization.
      Fertilization with manure, NP and methane also remarkably increased the number of
      actinomyces and the activities of urease, phosphatase and sucrase in soil. The
      activities of soil urease and phosphatase were increased by fertilization of
      manure, but little effect was found with fertilization of NP and methane.

PMID- 15506105
TI  - [Effect of straw return to field and fertilization in autumn on dryland corn
      growth and on water and fertilizer efficiency].
AB  - A ten years location experiment of various kinds straw return to field and deep
      fertilization in autumn was conducted in Shouyang dryland experimental area of
      Shanxi Province to study their effect on the growth and yield of dryland corn,
      the use efficency of soil water and fertilizer, and the changes of soil
      fertility. The results showed that this kind of experimental method could better
      solve the contradiction of deep fertilization with maintaining soil moisture and
      keeping a full stand of seedlings in spring, and the competition of water and
      fertilizer between the degradation of crop remains and the seedlings. What is
      more, the abundant resources of crop remains were used more sufficiently, the
      activity of soil microorganisms was more active, and soil fertility was obviously
      improved, which was proved by the complete and strong seedlings and developed
      roots, the photosynthesis and transpiration rates were enhanced, the water use
      efficiency (WUE) was increased by 3.26 - 3.51 kg x hm(-2) x mm(-1), and the
      accumulated water consumption was decreased by 8.1 - 264.5 mm. During plant
      growth period, the utilization rate of fertilizer N and P could increase 3.9% -
      13.9% and 3.0% - 9.1%, respectively, and the use efficiency of water and
      fertilizer was higher. The ten years accumulated yield increased 12.10 - 17.27 t
      x hm(-2), a rise of 25.6% - 36.5%, and in the meantime, higher soil fertility and
      productivity were maintained.

PMID- 15506106
TI  - [Biological availability of zinc lignosulfonate on calcareous soil of north
      Guoangdong Province].
AB  - Zinc lignosulfonate (Zn-LS) is a kind of organic fertilizers made from the by
      products of paper industry. With leach and plot treatments, this paper studied
      the difference of the biological availability between Zn-LS and an inorganic Zn
      fertilizer on calcareous soil of north Guangdong Province. The results indicated
      that the Zn of Zn-LS was less absorbed by calcareous soil. In soil B, when
      applying 10 mg x kg(-1) Zn, the dissolved amount of Zn-LS was 65.2% higher than
      that of inorganic Zn-fertilizer, corn grew well, and its biomass was higher. In
      soil A, when applying 10 mg x kg(-1) Zn of Zn-LS, the biomass of corn increased
      by 16.3%, and its Zn content was 81.2% higher. Therefore, biological availability
      of Zn-LS was better than that of inorganic Zn fertilizer.

PMID- 15506107
TI  - [Introdoction of bioluminescence genes into silicate-dissolving bacteria strain
      NBT].
AB  - In this study, silicate-dissolving bacteria NBT strain was grown with 0.25%
      maltose as carbon source, and the rifampicin-resistance was generated by
      ultraviolet mutagenesis and streak naturalized to 200 microg x ml(-1). Through
      triparental cross, the luxAB genes were introduced into NBT-R200 at the help of
      pRK2013. The luminescence activity of the hybrid strain was tested, which
      indicated that all colonies had a high luminescence activity and kanamycin-,
      tetracyctine-and rifampicin-resistance. The NBT-R200 cells prepared from initial
      logarithmic growth phage were more likely to be sensitive to foreign DNA, and the
      maximum translocation frequency was up to 6.70 x 10(-5). In addition, the optimal
      mating ratio was 1:1:1. The potassium release ability from feldspar and the
      luminescence of luxAB genes marked silicate-dissolving bacteria RL85 strain were
      stable, and hence, the RL85 was available to rhizosphere microecology researches.

PMID- 15506108
TI  - Microzooplankton grazing on phytoplankton in summer in the Jiaozhou Bay, China.
AB  - With dilution method, this paper studied the microzooplankton grazing on
      phytoplankton inside, outside and in a harbor area of the Jiaozhou Bay during
      June and July 2002. The dominant phytoplankton species outside and inside the bay
      were Cylindrotheca closterium and Skeletonema costatum, while the samples in the
      harbor had Skeletonema costatum, Eucampia zodiacus, and Chaetoceros curvisetus as
      the dominant species. The dominant microzooplankton species outside and inside
      the Jiaozhou Bay were Tintinnopsis beroidea and unidentified Strombidium sp.,
      while in the harbor, Strombidium sp. was the predominant microzooplankton species
      coexisted with few T. beroidea. The grazing rate of microzooplankton was 0.96 and
      1.20 d(-1) outside the bay, 1.33 d(-1) inside the bay, and 0.36 d(-1) in the
      harbor. The grazing rates of microzooplankton and the consumption percentages of
      potential primary production increased in turn from harbor area, outside the bay,
      to inside the bay. They were 74% and 84% outside the bay, 93% inside the bay, and
      53% in the harbor. The ingestion rate of phytoplankton carbon by microzooplankton
      was the highest in the harbor, with a value of 281 mgC x m(-3) x d(-1), the next
      was inside the bay, with a value of 102 mgC x m(-3) x d(-1), and the lowest was
      outside the bay, ranged from 31 to 49 mgC x m(-3) x d(-1). It seems that the
      phytoplankton community size structure and grazing behaviors of dominant
      microzooplankton species are the causes for these grazing differences. Compared
      with the similar studies in other bays around the world, the grazing pressure of
      microzooplankton in the Jiaozhou Bay is at the middle levels.

PMID- 15506110
TI  - [Photodegradation of 17beta-estradiol induced by Chlorella vulgaris].
AB  - The study showed that when exposed to high-pressure Hg-lamp (HPML, lambda(max) >
      or = 365 nm), and the concentration of Chlorella vulgaris was 4.0 x 10(10) cells
      x L(-1), the photodegradation rate of 17beta-estradiol could reach to 37%. When
      the concentration of Chlorella vulgaris was 4.2 x 10(10) cells x L(-1), the
      photodegradation of 1.5 x 10(-5) - 6.0 x 10(-5) mol x L(-1) 17beta-estradiol in
      aqueous solutions was pseudo-first order reaction. Increasing the initial
      concentration of 17beta-estradiol could lower its photodegradation rate. The
      influence of light intension and Chlorella vulgaris concentration on the
      photodegradation of 17beta-estradiol was also studied in this paper.

PMID- 15506109
TI  - [Interspecific interaction between Moina mongolica and Brachionus plicatilis].
AB  - In a laboratory experiment, Moina mongolica and Brachionus plicatilis were
      polycultured at four relatively inoculating densities, i.e., 0.06/0.30,
      0.10/0.30, 0.30/0.30 and 0.60/0.30 (ind x ml(-1)/ind x ml(-1)), while M.
      mongolica monocultured at 0.06, 0.10, 0.30 and 0.60 ind x ml(-1) and B.
      plicatilis at 0.30 ind x ml(-1) were used as the control. Interspecific
      interference did exist between M. mongolica and B. plicatilis when these two
      species coexisted in a microcosm. In the polycultured microcosms, depressed
      population density of M. mongolica resulted from the coexistence of B.
      plicatilis, and M. mongolica maintained at extremely low density. In opposite, M.
      mongolica had negligibly negative influence on the population of B. plicatilis.
      Further experiment showed that the mortality of M. mongolica deprived of food for
      120 h was 100%, while 90% of B. plicatilis survived after 144 h of food
      deprivation. The relatively strong capacity of B. plicatilis in tolerating
      starvation may be one of the important reasons for it wins the competition
      against M. mongolica.

PMID- 15506111
TI  - [Purification of eutrophic wastewater by Cyperus alternifolius, Coleus blumei and
      Jasminum sambac planted in a floating phytoremediation system].
AB  - In a greenhouse study, Cyperus alternifolius, Coleus blumei and Jasminum sambac
      were cultured in a floating phytoremediation system with plantation cups inserted
      into a polyfoam plate that floated in the upper part of a tank filled with 100 L
      domestic wastewater. The contents of chemical oxygen demand (CODCr), total P (T
      P), total N (T-N), soluble P(S-P), ammonia-nitrogen (NH4+ -N) and nitrate
      nitrogen (NO3- -N) in the domestic wastewater were tested during the growth of
      these three plants. The results showed that Cyperus alternifolius and Coleus
      blumei could grow well in the floating phytoremediation system, their dry weight
      being 285.8% and 371.4% of the initial weight of planting, respectively, but
      Jasminum sambac could not grow well, being 125.0% of the initial weight of
      planting. The removal rate of TN by these 3 plants was 68.0%, 62.0% and 45.0%,
      and that of NO3- -N, CODCr and TP was 98.0%, 80.0% and 92.0%, 78.0%, 66.0% and
      55.0%, and 90.6%, 90.5% and 88.0% respectively. Cyperus alternifolius and Coleus
      blumei had good effects on the removal of pollutants in the floating
      phytoremediation system.

PMID- 15506112
TI  - [On the methods of ecological security design for nature reserves].
AB  - Ecological damage and loss of natural habitats have been resulting in the
      fragmentation of wild animal and plant population, and nature reserves have
      become the islands of habitats. The traditional approach that focuses on a single
      and isolated nature reserve is not enough to protect biodiversity. Ecological
      processes and components of biodiversity in broad temporal and spatial scope
      should be protected, and a whole conservation network should be established.
      Based on the requirements and the trends of biodiversity conservation at home and
      abroad, this paper presented the concept of ecological security design for nature
      reserves, which is a coordinated planning strategy that integrates ecological,
      social and economic aspects. Firstly, a network of nature reserves is designed at
      regional level; secondly, the area, shape, internal zoning of a nature reserve is
      designed at the node (nature reserve) of the network; and finally, the
      connectivity between the network and nodes (corridors) is designed. Network
      design of nature reserves should maintain the regional integrity and the
      ecological process integrity of ecosystems. Iterative method, integer linear
      programming, and Geographic Approach (GAP) should be employed to provide
      blueprints of conservation planning for one or multiple conservation objectives.

PMID- 15506113
TI  - [Research advance in ecological and environmental water requirement].
AB  - This paper discussed the advance in ecological and environmental water
      requirement (EEWR) study, including its conception, classification, calculation
      methods, and others. At abroad, the EEWR study is concentrated on rivers, and a
      more applicable methodology has been established; while in China, it is focused
      on land and river in the interior river basins of the northwestern areas, the
      Yellow River Basin, the Haihe river basin and the Luanhe river basin, where the
      water shortage problem is serious. Many achievements of great significance in the
      EEWR study at home and abroad have been achieved, but there are still many other
      ambiguous and unknown issues to be further studied in the future, summarized as:
      (1) the studies on the EEWR theory (including its conception, classification,
      calculation methods, etc.) should be strengthened; (2) it is necessary to
      reinforce some aspects of the EEWR study, such as the internal and external
      affecting factors of EEWR, the engineering approaches or measures to meet EEWR,
      etc.; (3) it is urgent to expand the applied research of EEWR and to realize the
      optimized allocation of water resources.

PMID- 15506114
TI  - [Significance of senescence study on tree roots and its advances].
AB  - Root system is one of the important components of trees, and has some important
      physiological functions such as nutrient and water absorption, transport and
      storage, anchoring, and supporting. After tree root systems formed, roots often
      suffer from nutrient- and water-deficient stress, and thus, their absorption of
      nutrients and water appears more important. Soil nutrient and water have a great
      spatiotemporal heterogeneity. As the heterogeneity occurs, trees regulate carbon
      partitioning to roots, resulting in the senescence or death of some roots of the
      whole root system. In forestry, the senescence of tree roots is closely related
      to tree productivity, because there is a close relationship between the
      senescence of tree roots and the absorption of soil nutrient and water. At
      ecosystem and global scale, the senescence of tree roots influences the cycling
      of carbon and nutrients, because roots exhaust a great deal of carbon fixed by
      source leaves through photosynthesis, and there are great amounts of nutrients in
      tree roots. The senescence of tree roots is influenced by many environmental
      factors, biotic (e.g., fungi, bacteria, viruses, small edaphic animals) and
      abiotic (e.g., water, temperature, soil nutrients, heavy metals). These factors
      affect the senescence of tree roots by different mechanisms. Although we have
      much knowledge on the senescence of tree roots and some hypotheses have been
      proposed, some problems still remain to be resolved, and further experiments are
      needed to test these hypotheses. Interdisciplinary studies integrating cytology,
      biochemistry, soil science, and genetics are the prerequisite for rapid advances
      in understanding the essence of tree root senescence.

PMID- 15506115
TI  - [Potential ecological risks of transgenic trees].
AB  - A new approach to genetic improvement of trees has been introduced with the birth
      of gene engineering technique. Compared to that in crops, gene introduction in
      trees has bigger potential ecological risk in environmental release and
      extension, because trees, most of which are wind-dispersed, grow on various
      habitats, have longer life span, and subject to relatively more extensive
      management. Extensive plantation of transgenic trees may reduce the genetic
      diversity of the trees concerned. Co-evolution of pests and pathogens is likely
      to be caused under the pressure of long-term and continuous selection of the
      trees derived from gene transferring. Escaping of exogenous gene may have a
      certain kind of influence on fitness of plants naturally generated, and as a
      result, have influence on species diversity in the natural world. It is not
      reasonable for China, a developing country, to reject gene introduction as an
      approach to promote forestry development. It is also important, on the other
      hand, to take future ecological safety into consideration because it is unwise to
      get present profit at the cost of future profit. To strengthen basic study on
      gene transferring, adopting safe management of varieties generated from gene
      transferring and increasing funds on research and management of transgenic trees
      are believed to be measures to decrease, to the greatest extent, ecological risks
      brought about by gene transferring of trees, and to quicken transformation of
      products of trees derived from gene-transferring into merchandises.

PMID- 15506116
TI  - [Principle of "multiple ecological niche of one-species (variety)" and its
      application in high yield cotton cultivation].
AB  - The multiple ecological niche of one-species (variety) (MENOS) population is
      formed by one species (variety), but the ecological units have different
      temporal, spatial, nutritional, temperature, or water ecological niche. The
      formation of MENOS population is characterized by its specific object, one
      species (variety), multiple layer canopy, human being's active adjustment,
      specific niche breadth, and overlap and separation of ecological units. This
      paper analyzed the characteristics of the super high yield cotton population with
      dual ecological niche of one-species (variety) (DENOS). As for the yield
      components, MENOS has the characteristics of high yield canopy and different
      yield plants.

PMID- 15506117
TI  - [Designing cruxes and ecological issues of constructed wetland systems for
      wastewater treatment].
AB  - Constructed wetland system for wastewater treatment is an important technological
      mode of economical and high-effective ecological treatment of wastewater, but it
      is still necessary to develop and perfect in its performance, and in particular,
      to make a continuous improvement and systematic optimization in its technical
      parameters. In this paper, the designing cruxes of constructed wetland systems
      for wastewater treatment at home and abroad were summarily discussed, and the
      optimal models and most adaptable values for constructed wetland systems were
      given on the basis of technological parameters such as hydraulic residence time,
      hydraulic conduction factors, surface loading rate, and engineering-construct
      design. In the meantime, some ecological methods were recommended to solve the
      management of wild animals and mosquito problems resulted from the operation of
      constructed wetland systems for wastewater treatment.

PMID- 15506118
TI  - [Distribution of lichens biomass and its affecting factors during restoration
      process of Inner Mongolia steppe].
AB  - An experiment was installed in the typical steppe area of Central Inner Mongolia
      to study the distribution characteristics of lichen biomass in the restoration
      process. The experimental areas were continuously grazed for ten years (1989 to
      1998) under different stocking rate, and stopped grazing since 1999. Two years
      (2001 to 2002) monitoring on the distribution of lichen biomass and its affecting
      factors showed that no significant difference was found between different
      stocking rate treatments (P < 0.05). There existed positive correlations between
      lichen biomass and plant species diversity and between soil water content and
      soil organic matter content (P < 0.05), and negative correlations between lichen
      biomass and soil bulk density, and between Gramineae plant functional group and
      plant community coverage and biomass (P < 0.05).

PMID- 15506119
TI  - [Effect of bagging on greenhouse cucumber].
AB  - The study showed that culturing cucumber with film bag increased cucumber yield
      by 12.3% - 15.1%, reduced abnormal cucumber by 65.3% - 72.8%, and the shape of
      cucumber was straight and smooth. The keeping-fresh period of the cucumber
      prolonged to 20 - 25 days, its vitamin C increased 21.9%, and total sugar
      increased to 5.1%. Paper bagging increased cucumber yield by 7.2% - 10.1%, and
      reduced abnormal cucumber by 52.2% - 57.7%. Bag body could efficiently prevent
      the cucumber from the direct pollution of chemicals spray. The survival
      pesticides in film and paper bags was 0.760 mg x kg(-1) and 1.2208 mg x kg(-1),
      reduced by 83.3% and 73.2%, respectively, compared to non-bagging.

PMID- 15506120
TI  - [Lakartidningen focuses on clinical research and medical education].

PMID- 15506121
TI  - [The first study which shows structural cerebral cortex surface changes in
      children with ADHD].

PMID- 15506122
TI  - [Clinical research treads water between university and health care].

PMID- 15506123
TI  - ["Grounded theory" develops medicine. Popular research method for exploring human
      behavior can discover new connections].
AB  - Grounded theory (GT) is a popular research method for exploring human behavior.
      GT was developed by the medical sociologists Glaser and Strauss while they
      studied dying in hospitals in the 1960s resulting in the book "Awareness of
      dying". The goal of a GT is to generate conceptual theories by using all types of
      data but without applying existing theories and hypotheses. GT procedures are
      mostly inductive as opposed to deductive research where hypotheses are tested. A
      good GT has a core variable that is a central concept connected to many other
      concepts explaining the main action in the studied area. A core variable answers
      the question "What's going on?". Examples of core variables are: "Cutting back
      after a heart attack"--how people adapt to life after a serious illness; and
      "Balancing in palliative cancer care"--a process of weighing, shifting,
      compensating and compromising when treating people with a progressive and
      incurable illness trajectory.

PMID- 15506124
TI  - [Communication skills in the encounter with patients--current examination subject
      for medical students. Beneficial educational investment].
AB  - A continuous and structured training in communication skills for medical students
      still has a comparatively low priority in the curriculum of Swedish medical
      schools. A recent American study has demonstrated the value of incorporating such
      training programs during the early phase of medical studies. The effect of this
      reported intervention program was evaluated with objective structured clinical
      examination (OSCE). Significantly higher satisfaction in the medical encounter
      was documented among patients who met students trained in patient centeredness
      than among those who met students randomised to a control group. Thus,
      communication training for medical students improves specific competencies known
      to affect outcome of care. We report our experience with a similar model of a
      communication-training program during the first four semesters, with examination
      at the end of the program, which has been part of the pre-clinical curriculum
      since 1998 at the Karolinska Institute in Stockholm, Sweden.

PMID- 15506125
TI  - [Gamma knife surgery improves the treatment of intracranial tumors].
AB  - Radiosurgery is considered one of the most revolutionary recent developments in
      the therapy of certain intracranial tumors. It is generally accepted that
      radiosurgery with the Gamma Knife or stereotactic Linac is the least invasive
      effective treatment for cerebral metastases. The Gamma Knife provides so far the
      highest possible and practically applicable precision of radiation. Radiosurgery
      of brain metastases with a size of less than 12 cm3 results in excellent local
      tumor control rates and very low associated morbidity. The Gamma Knife has been
      shown to be highly effective also against multiple metastases and is likewise
      effective even for tumors that are relatively resistant to traditional external
      beam radiation therapy. Radiosurgery replaces open tumor operation in some
      indications. As an additive therapy it allows the conventional surgeon to operate
      less radically resulting in a lower complication rate. The goal is short
      hospitalization time and increased quality of life.

PMID- 15506126
TI  - [Perforated ulcer].

PMID- 15506128
TI  - [When discontinue cardiopulmonary resuscitation?].

PMID- 15506129
TI  - [County council sick leave committees support colleagues].

PMID- 15506127
TI  - [Esthetic surgery of the genitalia--is it a good idea?].

PMID- 15506131
TI  - [Could osteoarthritis have been prevented?].

PMID- 15506130
TI  - [Empathy test--an unreliable tool for gaining admission to medical studies].

PMID- 15506132
TI  - [Dilemma of physicians in adolescent health services].

PMID- 15506133
TI  - [Ankle joint arthritis in sarcoidosis--NSAID a good first choice medication].

PMID- 15506134
TI  - [Basis for development of a reference system for clinical decisions in liver
      disease].

PMID- 15506135
TI  - Which way for federalism and health policy?
AB  - The current balance of responsibility between states and the federal government
      for low-income people's health coverage has achieved a great deal. It covers many
      of the neediest people, supports the safety net, responds to emerging needs, and
      supports some experimentation. However, it leaves more than forty million people
      uninsured, allows excessive variation across states, places unsustainable
      pressure on state budgets, creates tension between the two levels of government,
      and yields too few benefits from experimentation. This mixed record argues for a
      significant simplification of and increase in eligibility for public programs,
      with the federal government either providing extra funds to states to meet these
      needs or assuming full responsibility for insuring the poor.

PMID- 15506136
TI  - Employer-sponsored health insurance and prescription drug coverage for new
      retirees: dramatic declines in five years.
AB  - Employer-sponsored health insurance is often described as the most reliable
      private source of Medicare supplementation, particularly for prescription drug
      benefits. This study's findings show that employer coverage is becoming an
      increasingly less dependable source of coverage for new retirees, and the problem
      is likely to get worse. We found that the proportion of Medicare beneficiaries
      ages 65-69 with employer coverage declined from 46 percent in 1996 to 39 percent
      in 2000. The proportion with drug coverage from an employer declined from 40
      percent in 1996 to 35 percent in 2000. Losses among males, the group most
      affected, would have been even greater had it not been for a slight increase in
      benefits from spouses' policies.

PMID- 15506137
TI  - Population-based disease management under fee-for-service Medicare.
AB  - Medicare policymakers are considering testing population-based disease management
      (PDM) programs under fee-for-service (FFS) Medicare as a way to improve health
      and cost outcomes for selected subgroups of chronically ill beneficiaries. This
      paper provides a brief overview of how PDM programs are evolving in the private
      sector and describes how they differ from other approaches already being tested
      in Medicare disease management demonstrations. It also discusses some key
      opportunities and issues to be considered in adapting PDM programs for testing in
      the FFS Medicare context.

PMID- 15506138
TI  - Floridian exceptionalism.
AB  - Elderly Floridians use much more medical care and have much lower mortality rates
      than do their peers in other regions of the country. After demographic and other
      variables are controlled for, the differential between Florida and the rest of
      the United States is 25 percent for utilization and 10 percent for mortality
      among whites ages 65-84. This paper summarizes the facts about Floridian
      exceptionalism and reviews various possible explanations: physician inducement of
      utilization, differences in preferences, selective migration into and out of the
      state, climate, and social interactions, among others. Readers are invited to
      suggest their own explanations and their policy recommendations, if any.

PMID- 15506139
TI  - Variation in use of medical care services: higher risk or higher consumption?
AB  - The issue of variation in use of medical care is important in Florida and in
      other regions of the country. It is difficult to disaggregate the effects of
      differences in health risk of Medicare beneficiaries from physicians' practice
      patterns and patients' preferences for care. New risk-adjustment methods used by
      the Centers for Medicare and Medicaid Services may provide some insights, but
      they also raise similar questions about the influence of practice patterns on
      variation.

PMID- 15506140
TI  - The need for evidence-based health policy to address health care variations.
AB  - Medicare policy making now deals mostly with price-setting issues. However, as
      Warren Buffet has noted: "Price is what you pay. Value is what you get." Victor
      Fuchs's studies raise fundamental issues for a value-oriented Medicare program.
      Florida offers one of many regional patterns of Medicare mortality that are not
      yet adequately explained. Valued-oriented, evidence-based Medicare policies would
      target opportunities to improve population health and would foster greater use of
      evidence-based medicine.

PMID- 15506141
TI  - Why are older Floridians exceptional?
AB  - Why do older Floridians have higher utilization of health care and live longer
      than other older Americans? Higher health care use among Florida's older
      residents is likely related to housing patterns, marital status, health insurance
      coverage, and ethnic composition. Lower mortality is unlikely a result of
      lifestyle factors or labor-force participation rates but may be associated with
      usage of preventive health care services. These indicators suggest that attention
      needs to be paid to health behavior and social support networks.

PMID- 15506142
TI  - Exceptionalism or extravagance? What's different about health care in South
      Florida.
AB  - In posing the "puzzle" of Florida exceptionalism, Victor Fuchs raises fundamental
      questions about Medicare's efficiency and equity. We agree that the higher
      spending in Florida has little to do with lower mortality rates. However,
      physicians and hospitals do play a large role in making South Florida different.
      Miami physicians are not more generous in providing heart, hip, or back surgery,
      procedures that beneficiaries seeking an active lifestyle might want. Instead,
      end-of-life care makes Miami truly exceptional: Patients in their last six months
      of life see more physicians and spend more time in intensive care than is the
      case virtually anywhere else in the world.

PMID- 15506143
TI  - Is there hope for the uninsured?
AB  - In an anecdote popular on the conference circuit, an American health policy
      analyst who has ascended to heaven asks God, "Will there ever be universal health
      insurance coverage in the United States?" "Perhaps," sighs God, "but not in my
      lifetime." This paper argues that this tale accurately describes the prospect of
      covering the uninsured in this country. Neither moral sentiments among a majority
      of U.S. political leaders, economic self-interest among those who would have to
      pay for universal health insurance, nor political pressure from the uninsured and
      likely-to-be-uninsured will provide a sufficiently strong imperative to move this
      country toward universal coverage soon, if ever.

PMID- 15506144
TI  - The politics of health reform: why do bad things happen to good plans?
AB  - This paper examines political feasibility and its implications for health reform.
      I discuss the political obstacles to health reform in the United States,
      disentangling perennial barriers from contemporary constraints. I then explore
      major reform options and their political prospects. I argue that while
      incremental reform now appears to be the most feasible option, the political
      climate may change in a way that permits a bolder vision. Moreover, incremental
      reform may not be sustainable in the long run, for the same reason that makes it
      politically popular now: It does not change the status quo in the health system.

PMID- 15506145
TI  - Americans' views of the uninsured: an era for hybrid proposals.
AB  - Data drawn from ten recent public opinion polls show that the issue of the
      uninsured is likely to become more visible on the U.S. agenda, although not as
      prominent as it was in the early 1990s. Although there is no public consensus on
      any single approach, a hybrid plan--which leaves workplace insurance in place and
      includes elements of several proposals now being discussed to cover more of the
      uninsured--offers the possibility of public support. The critical issue is
      whether or not there will be public support in the future for raising revenues to
      pay for major expansions in coverage.

PMID- 15506146
TI  - Building on the job-based health care system: what would it take?
AB  - Recent surveys indicate widespread public support for reforming health care by
      building on our mixed public/private system. The authors present a blueprint for
      such reform, along with design choices and their implications, that would improve
      access, cost control, and quality. Requiring employers to provide coverage, or at
      least to help workers obtain group insurance, combined with income-based premium
      subsidies, expanded public programs, and backup "insurance exchanges," would make
      affordable coverage available to nearly everyone. Cost control and quality
      improvement would be achieved mainly through pressures applied on the health care
      system by multiple, large purchasers that wield much buying power.

PMID- 15506147
TI  - A new Medicaid program.
AB  - This paper suggests a new federal-state partnership--a new Medicaid program--for
      coverage of the uninsured and long-term care. It discusses national eligibility
      standards, based on financial need (rather than categorical eligibility); buy-ins
      and reinsurance for high-risk populations; a national strategy of "Medicaid plus
      tax credits" to cover the uninsured; Medicaid long-term care with expanded
      eligibility, better financial protection, and home and community-based care
      benefits; quality initiatives; administration; and possible financing sources
      (such as estate taxes and an increased Social Security Disability Insurance wage
      base). Without a new mission and national standards, Medicaid will continue to
      grow in a patchwork fashion with huge gaps and inequities.

PMID- 15506148
TI  - The mental health commission tackles fragmented services: an interview with
      Michael Hogan.
AB  - Michael Hogan, chair of the President's New Freedom Commission on Mental Health,
      describes the commission's findings on the fragmentation of the public mental
      health services infrastructure and its effort to formulate strategies for
      improving the alignment of federal, state, and local policy and practice.
      Clinical treatment needs to be coordinated with supportive services such as
      housing, education, job training, and case management. State planning is crucial
      to harmonizing diverse revenue streams. Hogan notes the commission's efforts to
      include stakeholders in its deliberations and to initiate efforts to coordinate
      policies among the agencies represented by its members.

PMID- 15506149
TI  - Trends and variability in individual insurance products in California.
AB  - This paper examines recent trends in benefits and premiums for individual health
      insurance products purchased by Californians. There is much variability in the
      coverage available in the individual insurance market, with correspondingly wide
      variability in premiums. Despite concerns about increased consumer cost sharing,
      the average share of health spending covered by these products has remained
      constant between 1997 and 2002. Whether this trend can continue in the face of
      higher health costs is unclear.

PMID- 15506150
TI  - Who enrolls in a program for parents of publicly insured children?
AB  - Although interest in expanding SCHIP coverage to parents has grown over the past
      five years, few such expansions have actually been implemented. State governments
      and health plan administrators remain concerned that these expansions will
      attract only high-risk enrollees, resulting in costly premiums that require large
      subsidies. We examine characteristics of enrollees in an SCHIP-like expansion
      program in Alameda County, California. According to our survey data, the program
      did not experience unfavorable selection. Rather, it attracted a broad range of
      eligible adults. Enrollees were comparable to the overall low-income population
      in Alameda County in terms of age, health status, and various utilization
      measures.

PMID- 15506151
TI  - Can hospitals and physicians shift the effects of cuts in Medicare reimbursement
      to private payers?
AB  - Leaders of health insurance companies, hospital systems, and physician
      organizations believe that when Medicare and Medicaid reduce payment rates to
      hospitals or physicians, these providers respond by raising prices to private
      insurers to offset a portion of the loss in revenue. This would mean that payment
      reductions in public programs contribute to increasing premiums for private
      insurance. But on both theoretical and empirical grounds, economists have been
      skeptical about the existence of this "cost shifting." I show that more realistic
      models of the behavior of hospitals and physicians than exist in basic economics
      texts provide a conceptual basis for cost shifting.

PMID- 15506152
TI  - Medicare payment policy: does cost shifting matter?
AB  - We examine cost shifting within the context of Medicare payment policy. We
      briefly review economic theory and available data and discuss the importance of
      cost shifting for policy. Then we present four central findings on cost shifting
      based on the views of former high-level policymakers. First, Medicare's early
      (pre-prospective) payment policy was a boon to hospitals. Second, Medicare
      payment policy is a "top-down" affair, driven by budgetary and special-interest
      politics. Third, federal policymakers may not consciously consider cost shifting,
      but state policymakers do. Fourth, Medicare payment policy requires constant
      adjustment, but we are "getting it right" most of the time.

PMID- 15506153
TI  - Cost shifting: new myths, old confusion, and enduring reality.
AB  - The papers by Paul Ginsburg and Jason Lee and colleagues make it clear how far we
      have come on the issue of cost shifting and how far we still have to go. We have
      created some new myths, persisted in some old confusion, and largely ignored an
      enduring reality. That enduring reality is that lack of competition in the health
      care sector permits cost shifting to occur. Instead of focusing on this causal
      condition, public discussion has been centered on the symptoms. A number of steps
      can be taken to deal with causes; this paper discusses several of these steps.

PMID- 15506155
TI  - The federal smallpox vaccination program: where do we go from here?
AB  - Despite the underwhelming response to the federal government's initiative to
      inoculate health care workers against smallpox, the Bush administration has
      indicated that the program will continue and that it could be expanded to include
      other health care providers, emergency service workers, and others deemed
      essential for continuity of government. We discuss the reasons for the program's
      failure to date, outline recent advisories questioning the extent of the
      vaccination effort, and suggest suspension of further vaccination efforts until
      certain questions and issues are resolved.

PMID- 15506154
TI  - How different is California? A comparison of U.S. physician organizations.
AB  - Data from a national study of medical groups and independent practice
      associations are used to examine the extent to which California physician
      organizations are different from physician organizations in the rest of the
      United States. California physician organizations are different in many ways:
      most notably, they are more likely to have external incentives to improve quality
      and more likely to use recommended care management processes for treating
      patients with chronic illnesses. The implications of these differences for policy
      and practice are discussed.

PMID- 15506156
TI  - Politics, technology, and transformation: a conversation with Newt Gingrich.
AB  - In this interview conducted by Jeff Goldsmith, former congressman and Speaker of
      the House Newt Gingrich (R-GA) provides an iconoclastic view of the problem of
      reforming a Medicare system in the absence of a political consensus about what
      needs reforming. Topics include Medicare prescription drug legislation, the role
      of technology in transforming the health care system, the need to communicate
      clearly and honestly with people (especially senior citizens) about proposed
      changes to their health benefits, the role of the private sector, and incentives
      for change.

PMID- 15506157
TI  - Prices and availability of pharmaceuticals: evidence from nine countries.
AB  - This study compares average price levels for pharmaceuticals in eight countries-
      Canada, Chile, France, Germany, Italy, Japan, Mexico, and the United Kingdom-
      relative to the United States. Our most comprehensive indexes, adjusted for U.S.
      manufacturer discounts, show Japan's prices to be higher than U.S. prices, and
      other countries' prices ranging from 6 percent to 33 percent lower than U.S.
      prices. The decline of the Canadian dollar and rise of the U.K. pound contribute
      to the finding of lower Canadian prices and higher U.K. prices in 1999 than in
      1992. Our findings suggest that U.S.-foreign price differentials are roughly in
      line with income and smaller for drugs than for other medical services.

PMID- 15506158
TI  - The relationship between technology availability and health care spending.
AB  - We analyze the relationship between the supply of new technologies and health
      care utilization and spending, focusing on diagnostic imaging, cardiac, cancer,
      and newborn care technologies. As anticipated by previous research, increases in
      the supply of technology tend to be related to higher utilization and spending on
      the service in question. In some cases, notably diagnostic imaging, increases in
      availability appear associated with incremental utilization rather than
      substitution for other services. Policy efforts to assess and manage the
      availability of new technologies could benefit society where the additional
      spending produced by new services is not associated with strong quality
      improvements.

PMID- 15506159
TI  - Uncovering the health challenges facing people with disabilities: the role of
      health insurance.
AB  - Americans with disabilities have wide-ranging health care needs and face serious
      challenges in the health care system. This 2003 survey of 1,505 nonelderly adults
      with disabilities finds relatively large shares of people with disabilities
      reporting cost-related barriers to care. The study also reveals marked
      differences in cost-related experiences both between those with and without
      health insurance and across sources of coverage. These findings suggest the need
      for additional research, along with policies to provide health insurance to
      people with disabilities who lack coverage, to fill gaps in coverage among those
      with Medicare and private insurance, and to maintain coverage for Medicaid
      enrollees amid rising costs and state budget shortfalls.

PMID- 15506160
TI  - The effects of cash and counseling on personal care services and Medicaid costs
      in Arkansas.
AB  - The Cash and Counseling Demonstration gives Medicaid beneficiaries who are
      eligible for personal care services a consumer-directed allowance in lieu of
      traditional agency services. Using survey and Medicaid claims data on 2,008 adult
      applicants randomly assigned to treatment or control groups, we find the program
      increased the receipt of paid care but reduced unpaid care. The treatment group
      had higher Medicaid personal care expenditures than controls did, because many
      controls received no paid help, and recipients obtained only two-thirds of
      entitled services. By the second year after enrollment, these higher personal
      care expenditures were offset by lower spending for nursing homes and other
      Medicaid services.

PMID- 15506161
TI  - African Americans' views on health policy: implications for the 2004 elections.
AB  - In the competition for African American voters in the 2004 elections, health
      policy is likely to be an important issue. Blacks are about twice as likely as
      whites to say that health care issues are important in their vote choice. Using
      national survey data, this paper shows that candidates will have to have well
      developed proposals on the uninsured, protecting Medicaid, aiding neighborhood
      health centers, and expanding funding for AIDS, to appeal to black voters.
      However, in responding to black voters, candidates will have to be careful not to
      alienate white voters by proposing health policies that involve sizable increases
      in taxes or government regulation.

PMID- 15506162
TI  - Getting serious about excessive Medicare spending: a purchasing model.
AB  - It is now well documented that Medicare spending varies widely across the country
      and that higher spending does not produce differences in quality, access, or even
      patient satisfaction. Yet for various reasons, policy analysts have tended to
      minimize the importance of the fact that as much as 30 percent of Medicare
      spending might be excessive and unnecessary. There is an imperative to transform
      the traditional Medicare program from that of a claims payer to that of a
      strategic purchaser, able to adopt a broad array of approaches and to use a
      comprehensive set of tools used by private plans, but in a more transparent and
      accountable way.

PMID- 15506163
TI  - Reducing the growth of Medicare spending: geographic versus patient-based
      strategies.
AB  - This paper explores the potential of two alternative approaches for reducing the
      rate of growth in Medicare spending. One strategy would focus on reducing the
      expenditures of high-spending individuals. Given that a large share of Medicare
      spending is consumed by relatively few beneficiaries, this approach targets the
      small group responsible for most of the spending. The other strategy would focus
      on reducing expenditures in high-spending regions. Because either approach would
      have to overcome major hurdles before lowering Medicare spending, the likely
      payoff from the alternative strategies is far from clear. Viewed from a budgetary
      perspective, concentration in Medicare spending suggests the importance of
      focusing on high-spending patients.

PMID- 15506164
TI  - Addressing variations: is there hope for the future?
AB  - The papers by Robert Berenson and by Steven Lieberman and colleagues show that
      variations remain a true challenge for those trying to improve the delivery of
      health care. Recent clarifications in the understanding of unwarranted variations
      allow us to address variations in a more logical and manageable fashion. In this
      Perspective we describe key challenges in addressing variations in the context of
      these recent clarifications. The Centers for Medicare and Medicaid Services (CMS)
      needs to move forward on information-sharing interventions and use demonstrations
      to pursue innovative strategies to improve the delivery of care through its
      purchasing power.

PMID- 15506165
TI  - Approval times for new drugs: does the source of funding for FDA staff matter?
AB  - The Food and Drug Administration (FDA) has been criticized for injudicious and
      excessively rapid approval of new drugs as a result of pharmaceutical industry
      influence. Many critics focus on the Prescription Drug User Fee Act (PDUFA) of
      1992, which augmented the FDA's budget through the charging of user fees. We
      assess the effect of FDA staffing patterns and attributes of submitting firms on
      approval times for 843 new drug applications (NDAs) submitted between 1977 and
      2000. NDA review times shortened by 3.3 months for every 100 additional FDA
      staff. The amount of funding for FDA staff appears to be a much more important
      influence on NDA review time than the source of funding.

PMID- 15506166
TI  - Explaining reductions in FDA drug review times: PDUFA matters.
AB  - Yale professor Mary Olson responds to the paper titled "Approval Times for New
      Drugs: Does the Source of Funding for FDA Staff Matter?" by Daniel Carpenter and
      colleagues (Health Affairs Web Exclusive, 17 December 2003). According to her
      analysis, the Prescription Drug User Fee Act (PDUFA) of 1992, which introduced
      user fees for new-drug review, had a greater impact on reducing drug approval
      times than the analysis of Carpenter and colleagues found. Olson's analysis
      examined review times aggregated by year of approval, instead of the year that
      the drug application was submitted. She found that even after increased agency
      resources over time were controlled for, the user fee reform led to a substantial
      reduction in drug review times. She also found that there was little reduction in
      drug review times until after user fees were introduced.

PMID- 15506167
TI  - Targeted gene delivery to human airway epithelial cells with synthetic vectors
      incorporating novel targeting peptides selected by phage display.
AB  - Human airway epithelial cell targeting peptides were identified by biopanning on
      1HAEo-cells, a well characterised epithelial cell line. Bound phage were
      recovered after three rounds of binding, high stringency washing and elution,
      leading to the production of an enriched phage peptide population. DNA sequencing
      of 56 clones revealed 14 unique sequences. Subsequent binding analysis revealed
      that 13 of these peptides bound 1HAEo-cells with high affinity. Three peptides,
      SERSMNF, YGLPHKF and PSGAARA were represented at high frequency. Three clearly
      defined families of peptide were identified on the basis of sequence motifs
      including (R/K)SM, L(P/Q)HK and PSG(A/T)ARA. Two peptides, LPHKSMP and LQHKSMP
      contained two motifs. Further detailed sequence analysis by comparison of peptide
      sequences with the SWISSPROT protein database revealed that some of the peptides
      closely resembled the cell binding proteins of viral and bacterial pathogens
      including Herpes Simplex Virus, rotavirus, Mycoplasma pneumoniae and rhinovirus,
      the latter two being respiratory pathogens, as well as peptide YGLPHKF having
      similarity to a protein of unknown function from the respiratory pathogen
      Legionella pneumophila. Peptides were incorporated into gene delivery
      formulations with the cationic lipid Lipofectin and plasmid DNA and shown to
      confer a high degree of transfection efficiency and specificity in 1HAEo-cells.
      Improved transfection efficiency and specificity was also observed in human
      endothelial cells, fibroblasts and keratinocytes. Therefore, on the basis of
      clone frequency after biopanning, cell binding affinity, peptide sequence
      conservation and pathogenic similarity, we have identified 3 novel peptide
      families and 5 specific peptides that have the potential for gene transfer to
      respiratory epithelium in vivo as well as providing useful in vitro transfection
      reagents for primary human cell types of scientific and commercial interest.

PMID- 15506168
TI  - Prime-boost vaccination based on DNA and protein-loaded microspheres for
      tuberculosis prevention.
AB  - We evaluated the use of a vaccine formulation based on a mixture of two different
      PLGA microspheres, composed by faster and slower release profiles, containing DNA
      encoding hsp65 and the recombinant hsp65 protein, respectively, aiming to DNA
      priming and protein boost after a single dose vaccination. The combination of
      PLGA50:50 microspheres containing DNA-hsp65 and trehalose dimycolate (TDM) with
      PLGA75:25 microspheres containing recombinant hsp65 (prime-boost Me) was able to
      induce high levels of anti-hsp65 specific antibodies. The serum levels of these
      specific antibodies remained high during 90 days after vaccination, whereas the
      DNA Me formulation based only in DNA-hsp65 plus TDM-loaded microspheres was not
      able to sustain the high antibody levels during the same period. Production of
      IFN-gamma was significant in animals vaccinated with both formulations, while the
      prime-boost Me vaccinated mice sustained higher levels of this cytokine during
      all the evaluation period. Thus, prime-boost strategy by using biodegradable
      microspheres seems to be a promising strategy to stimulate long-lasting immune
      response.

PMID- 15506169
TI  - Photochemically enhanced gene delivery of EGF receptor-targeted DNA polyplexes.
AB  - Epidermal growth factor receptor (EGFR) targeted DNA polyplexes, containing
      polyethylenimine (PEI) conjugated with EGF protein as cell-binding ligand for
      endocytosis and polyethylene glycol (PEG) for masking the polyplex surface
      charge, mediated a 3- to 30-fold higher luciferase gene expression in HUH7, HepG2
      and A431 cell transfections than analogous untargeted PEG-PEI polyplexes.
      Transfection levels can be further enhanced by treatment of cells with
      amphiphilic photosensitizers followed by illumination. In this process
      photosensitizers localized in membranes of endocytic vesicles are activated by
      light, resulting in the destruction of endocytic membrane structures and
      releasing co-endocytosed polyplexes into the cell cytosol. Photochemical enhanced
      gene expression was observed in all cell lines, with the magnitude of enhancement
      depending on the particular PEI polyplex formulation and cell line, ranging
      between 2- and 600-fold. Importantly, improved gene transfer retained EGF
      receptor specificity, as demonstrated by comparison with ligand-free polyplexes
      and by receptor antibody or ligand competition experiments. These results suggest
      that this combined procedure enables a dual mode of targeting polyplexes:
      biological targeting via EGFR interaction, combined with physical targeting with
      light to direct a photochemical delivery of therapeutic genes to a desired
      location.

PMID- 15506170
TI  - Peptide-mediated gene transfer of cationic lipid/plasmid DNA complexes to
      endothelial cells.
AB  - The purpose of this research is to develop ligand-targeted plasmid based gene
      delivery systems for gene transfer to tumor endothelium. Cell adhesion assays
      were used to test the peptide inhibition of human endothelial cell adsorption to
      vitronectin-treated tissue culture plates. A series of RGD containing peptides
      were tested in linear form and with one and two disulfide bonds. The linear and
      two disulfide bond peptides yielded similar IC50 (approximately 1 x 10(-7) M).
      Substitution of two methionines for cysteines yielded a single disulfide bond
      that increased the IC50 by 10-fold. The single and double disulfide peptides were
      derivatized to N-succinyl-dioleoylphopsphatidylethanolamine and incorporated into
      100 nm liposomes radiolabeled with H-cholesterylhexadecylether. Liposome uptake
      by human umbilical vein endothelial cells was tested as a function of lipopeptide
      surface density. Increase in membrane surface density from 5 to 20mol% increased
      human umbilical derived endothelial cell (HUVEC) uptake of the liposomes for both
      the single and double disulfide peptides. Liposome uptake by HUVECs was 3-fold
      greater for the double disulfide compared to the single disulfide. The single and
      double disulfide lipopeptides were then tested for gene transfer to HUVECs using
      DOTMA:Cholesterol cationic liposomes. The polyplexes were formed by rapidly
      mixing plasmid DNA with DOTMA:CHOL liposomes at a 3:1 charge ratio in 2% ethanol,
      10% lactose. The ethanol was removed by lyophilization and upon rehydration, the
      lipoplexes had a mean diameter of approximately 100nm. HUVEC transfection studies
      showed that increasing the mol% of the single disulfide RGD lipopeptide to 20mol%
      increased gene transfer by 10-fold. This increase in transfection could be
      reduced to that obtained in the absence of lipopeptide by co-incubating the
      HUVECs with a 100-fold excess of the single disulfide RGD peptide, thus
      demonstrating lipopeptide mediated gene transfer to endothelial cells.

PMID- 15506171
TI  - Genuine DNA/polyethylenimine (PEI) complexes improve transfection properties and
      cell survival.
AB  - Polyethylenimine (PEI) has been described as one of the most efficient cationic
      polymers for in vitro gene delivery. Systemic delivery of PEI/DNA polyplexes
      leads to a lung-expression tropism. Selective in vivo gene transfer would require
      targeting and stealth particles. Here, we describe two strategies for chemically
      coupling polyethylene glycol (PEG) to PEI, to form protected ligand-bearing
      particles. Pre-grafted PEG-PEI polymers lost their DNA condensing property, hence
      their poor performances. Coupling PEG to pre-formed PEI/DNA particles led to the
      expected physical properties. However, low transfection efficacies raised the
      question of the fate of excess free polymer in solution. We have developed a
      straightforward a purification assay, which uses centrifugation-based
      ultrafiltration. Crude polyplexes were purified, with up to 60% of the initial
      PEI dose being removed. The resulting purified and unshielded PEI/DNA polyplexes
      are more efficient for transfection and less toxic to cells in culture than the
      crude ones. Moreover, the in vivo toxicity of the polyplexes was greatly reduced,
      without affecting their efficacy.

PMID- 15506172
TI  - A novel method for polymer coating of plasmid DNA: initial investigations into
      the use of pulse laser deposition and gene delivery.

PMID- 15506173
TI  - Salmon flame retardant research raises new questions.

PMID- 15506174
TI  - A nationwide census of airborne bacteria.

PMID- 15506175
TI  - UK to tackle endocrine disrupters in wastewater.

PMID- 15506176
TI  - Taiwan to reduce some greenhouse gases.

PMID- 15506177
TI  - Is smart growth better for water quality?

PMID- 15506178
TI  - When synthetic chemicals degrade in the environment.

PMID- 15506179
TI  - Nano-PV set to accelerate solar-energy use.

PMID- 15506180
TI  - Polychlorinated naphthalenes in Swedish background air.
AB  - Polychlorinated naphthalenes (PCNs) with four to eight chlorines were studied in
      air collected at two background stations in Sweden, one southerly and one
      northerly. Air was sampled with a high-volume sampler, and gas-phase adsorbents
      and filters were analyzed separately. The sum of TeCNs to HxCNs in the gaseous
      phase ranged between 1 and 10 pg/m3 with significantly higher concentrations at
      the southern location Hoburgen. HpCNs and OCN were below the detection limit. The
      highest concentrations were found in two samples from Hoburgen with the air
      masses coming from SW and W and during warm weather (+11 degrees C). The lowest
      concentration was found in a sample from the northern location Ammarnas at cold
      weather (-22 degrees C) when the air came from the east. A correlation was found
      between logP and 1/T indicating that temperature has a larger effect than
      location on the concentration in the gas phase. The TeCNs constituted 50-75% in
      the gaseous phase. In most filter samples TeCNs and PeCNs were below the limit of
      quantitation. PUF samples with air trajectories from W to NE had relatively
      higher concentrations of late eluting TeCNs and PeCNs, while in samples with
      winds from SE to S the early eluting congeners dominated. Samples with early
      eluting congeners were mainly collected at lower temperature. TriCNs constituted
      the dominant homologue group both in the gaseous and particulate phase of air
      samples as well as in bulk deposition from a rural monitoring station south of
      Stockholm. The octanol-air partition coefficient described the gas/particle
      interaction well for samples collected at temperatures down to -8 degrees C.

PMID- 15506181
TI  - Redox chemistry in Minnesota streams during episodes of increased methylmercury
      discharge.
AB  - Mercury (Hg) and methylmercury (MeHg) are flushed from watersheds during
      hydrological events, contaminating downstream surface waters and resident fish
      populations. We monitored total mercury (THg), MeHg, and ancillary water
      chemistry parameters in two streams (Cedar Creek and Trott Brook) in east-central
      Minnesota on a weekly or semiweekly basis from April through October 2003. Heavy
      precipitation in late June resulted in discrete episodes of high concentrations
      (>1.2 ng/L) of MeHg in both streams in early July. The MeHg/THg ratio increased
      from 0.15 to 0.36 in Cedar Creek and from 0.13 to 0.46 in Trott Brook during the
      event. The high MeHg concentrations were accompanied by low dissolved oxygen
      concentrations and increased concentrations of dissolved organic carbon, Mn, Fe,
      and orthophosphate. A prolonged absence of precipitation during August and early
      September brought stream levels back to baseflow values, and MeHg concentrations
      decreased to less than 0.1 ng/L. These results suggest that warm-weather, high
      discharge events are the primary route of export of MeHg from these watersheds,
      and baseflow contributes much less MeHg to downstream waters. The redox water
      chemistry during the,events sampled here suggests that MeHg in these streams is
      discharged from wetland areas where anoxic/anaerobic conditions prevail.

PMID- 15506182
TI  - Polycyclic aromatic hydrocarbon sources related to biomarker levels in fish from
      Prince William Sound and the Gulf of Alaska.
AB  - Seafloor sediments in Prince William Sound (PWS) and the eastern Gulf of Alaska
      (GOA) have a substantial regional hydrocarbon background from natural sources
      including oil seeps and eroding sedimentary rocks along the eastern GOA coast.
      Polycyclic aromatic hydrocarbons (PAH) from that background appear to be
      bioavailable to fish. Fish collected from PWS and the GOA in a 1999--2000
      biomarker study (bile fluorescent aromatic contaminants and liver ethoxyresorufin
      O-deethylase) show evidence of exposure to low levels of PAH at all categories of
      sites sampled. Seafloor sediments at fish sampling sites in the GOA east of PWS
      and at three PWS site categories (nonspill path, spill path oiled, and spill path
      not oiled) contain hydrocarbons from four principal sources: regional background,
      combustion products, residues from the 1989 Exxon Valdez oil spill (EVOS), and
      Monterey (CA) petroleum residues. GOA sediments between PWS and Yakutat Bay,
      approximately 350 km to the east, are dominated by regional petrogenic background
      hydrocarbons (total PAH (TPAH) range approximately 60-3400 ng/g) that are the
      probable cause of low biomarker levels measured in halibut from this area. PWS
      sediments contain varying proportions of regional background, combustion
      products, Monterey residues, and EVOS residues at some spill path sites. Rockfish
      caught in PWS embayments in 1999 have liver EROD activities that correlate
      positively with the pyrogenic PAH indicator ratio (FI+Py)/C24Ph. Although traces
      (<5-100 ng/g TPAH) of EVOS residues were detected in seafloor sediments at some
      nearshore spill path sites, biomarker levels in fish from those sites are not
      elevated relative to other sites in PWS.

PMID- 15506183
TI  - Source identification of PCDD/Fs for various atmospheric environments in a highly
      industrialized city.
AB  - This study set out to identify possible PCDD/F emission sources for different
      atmospheric environments in a highly industrialized city located in southern
      Taiwan. We collected stack flue gas samples from five main stationary emission
      sources of the municipal solid waste incinerators (MSWIs), medical waste
      incinerators (MWIs), electric arc furnaces (EAFs), secondary aluminum smelters
      (ALSs), and sinter plants to assess the characteristics of their PCDD/F
      emissions. For mobile sources, congener profiles reported in U.S. EPA's database
      for unleaded gas-fueled vehicles (UGFV) and diesel-fueled vehicles (DFV) were
      directly adopted owing to lack of local data. The congener profiles of the
      2,3,7,8-substituted PCDD/Fs were selected as the signatures of these PCDD/F
      emission sources. We conducted PCDD/F samplings on atmospheric environments of
      four categories, including background, residential area, traffic area, and
      industrial area. Through PCA and cluster analyses, we found that traffic areas
      were most influenced by PCDD/F emissions from UGFV and DFV, while those of
      industrial areas were mainly influenced by metallurgical facilities and MWIs. The
      above results were further examined by using the methodology of the indicatory
      PCDD/Fs. We confirmed that traffic areas were contributed by traffic sources, but
      industrial areas were simply affected by metallurgical facilities rather than
      MWIs. In conclusion, besides the use of PCA and cluster analyses, the methodology
      of the indicatory PCDD/Fs should be conducted for further validation in order to
      prevent misjudgment.

PMID- 15506184
TI  - Global assessment of polybrominated diphenyl ethers in farmed and wild salmon.
AB  - We have shown recently that levels of persistent, bioaccumulative contaminants
      (polychlorinated biphenyls, dioxins, and several chlorinated pesticides) are
      significantly higher in farmed than in wild salmon and that European farm-raised
      salmon have significantly greater toxic contaminant loads than those raised in
      North and South America. In this paper, we extend these results to polybrominated
      diphenyl ethers (PBDEs) and show that farm-raised salmon have higher levels of
      these compounds than wild salmon. We also show that farm-raised salmon from
      Europe have higher PBDE levels than those raised in North America and that both
      European and North American farm-raised salmon have higher PBDE levels than those
      farm-raised in Chile. Among the species of wild salmon, chinook had significantly
      elevated PBDE levels relative to the other wild species. These elevated PBDE
      levels may be related to chinook's feeding behavior and trophic level. Among all
      of the wild species we studied, chinook tend to feed higher in the food web
      throughout their adult life and grow to be larger individuals.

PMID- 15506185
TI  - Enantiomeric specificity of methylsulfonyl-PCBs and distribution of bis(4
      chlorophenyl) sulfone, PCB, and DDE methyl sulfones in grey seal tissues.
AB  - PCB methyl sulfones (MeSO2-PCBs) are lipophilic PCB metabolites of which five of
      the environmentally relevant meta/para pairs are chiral (i.e., exist as
      atropisomeric pairs). Methylsulfonyl-DDE (MeSO2-DDE) is a DDE metabolite, while
      bis(4-chlorophenyl) sulfone (BCPS) is a commercial monomer used for thermoplastic
      production. All these sulfones are well-known environmental contaminants. In this
      study, liver, lung, and adipose tissue in grey seals (Halichoerus grypus) from
      the Baltic Sea, naturally exposed to organochlorines via their food, were
      analyzed for the compounds mentioned. MeSO2-PCBs, 3-MeSO2-DDE, and BCPS were all
      found in significantly higher concentrations in the liver than in lung and
      blubber. Their strong liver retention, represented by a median of 42 microg/g
      l.w. of sigmaMeSO2-PCBs, has previously been mainly neglected in assessments of
      exposure. The highest concentrations of PCBs and DDE were still found in the grey
      seal blubber. The atropisomeric composition of MeSO2-PCB congeners was
      determined, and their enantiomeric fractions were calculated and compared in
      blubber, liver, and lung tissues. The enantiomeric specificity was equal in all
      tissues. A notably high abundance (>94%) was observed for one atropisomer in each
      chiral MeSO2-PCB pair. The first eluting atropisomer (A1) was dominating for all
      para-substituted MeSO2-PCBs studied, while the second eluting atropisomers (A2)
      were as dominant in all meta-substituted MeSO2-PCBs in all samples analyzed. In
      the liver, as much as 50% of sigmaMeSO2-PCBs consisted of the second eluting
      atropisomer (A2) of 5-MeSO2-CB149. The results imply that the sulfone group is
      crucial for the specific liver retention of MeSO2-PCBs, 3-MeSO2-DDE, and BCPS.

PMID- 15506186
TI  - Investigations into the vertical distribution of PCDDs and mineralogy in three
      ball clay cores from the United States exhibiting the natural formation pattern.
AB  - In this study, we report the PCDD and mineralogical results from the analyses of
      27 different samples from three ball clay cores from different locations in
      Kentucky and Tennessee. One goal of this study was to determine if there is a
      correlation between the mineralogy of the ball clay samples and the PCDD
      concentrations and/or homologue profiles in each sample. Samples from each of the
      three cores exhibited the natural formation profile with extremely high PCDD
      concentrations with low and mostly undetectable levels of polychlorinated
      dibenzofurans (PCDFs). The maximum toxic equivalents (TEQs) for Cores C-E were
      2500, 440, and 15,000 pg WHO-TEQ/g, respectively. Although there does not seem to
      be a direct correlation between mineralogy and PCDD concentrations or homologue
      profiles, the mineralogy of Core C is substantially different than that of Cores
      D and E, which may in part explain the differences in congener patterns we
      observed among the three cores.

PMID- 15506187
TI  - Atmospheric mercury accumulation rates between 5900 and 800 calibrated years BP
      in the High Arctic of Canada recorded by peat hummocks.
AB  - In this paper, we present the first comprehensive long-term record of
      preanthropogenic rates of atmospheric mercury accumulation in dated peat deposits
      for the High Arctic of Canada. Geochemical studies of two peat hummocks from
      Bathurst Island, Nunavut reveal substantial inputs from soil dust (titanium),
      marine aerosols (bromine), and mineral-water interactions (uranium). Mercury,
      however, was supplied to these peat mounds exclusively by atmospheric deposition.
      Mercury concentration measurements and age dating of the peat profiles indicate
      rather constant natural "background" mercury flux of ca. 1 microgram per square
      meter per year from 5900 to 800 calibrated years BP. These values are well within
      the range of the mercury fluxes reported from other Arctic locations, but also by
      peat cores from southern Canada that provide a record of atmospheric Hg
      accumulation extending back 8000 years. Thus, preanthropogenic Hg fluxes in the
      Arctic were not significantly different from atmospheric Hg fluxes in the
      temperate zone. In preindustrial times, therefore, the High Arctic was no more
      important as a sink for global atmospheric mercury than was the temperate zone.

PMID- 15506188
TI  - Gas-particle partitioning of polycyclic aromatic hydrocarbons in urban, adjacent
      coastal, and continental background sites of western Greece.
AB  - Particle- and gas-phase polycyclic aromatic hydrocarbons (PAHs) were collected
      from an urban, an adjacent coastal, and a continental background site located in
      Eordea basin, western Greece, to investigate their gas/ particle distributions.
      Thirteen two- to six-ring PAHs, included in the U.S. EPA priority pollutant list,
      were determined in 24-h integrated glass fiber filters and polyurethane foam
      samples. At the prevailing ambient temperature levels, the three-ringed species
      (phenanthrene, anthracene) and the four-ringed fluoranthene and pyrene were
      primarily found in the gas phase. Conversely, the five- and six-ring PAHs were
      mainly associated with the particle phase. Gas/particle partitioning
      coefficients, Kp, were calculated, and their relationship with the subcooled
      liquid vapor pressure p degrees L of individual PAHs was investigated. Despite
      the large variability among samples, a good linear relationship between log Kp
      and log p degrees L was obtained for all sampling sites following the equation
      log Kp = m(r) log p degrees L + b(r). In the majority of sampling events,
      particularly in the adjacent coastal and the continental background sites, slopes
      (m(r)) were found to be shallower than the value of -1, which has been suggested
      as reflecting equilibrium partitioning. The deviations from predicted aerosol
      behavior observed in the present study may be attributed to several reasons, such
      as the presence of nonexchangeable PAH fraction, nonequilibrium as well as
      different particle characteristics.

PMID- 15506189
TI  - Kinetics of trace metal competition in the freshwater environment: some
      fundamental characteristics.
AB  - Freshwaters are recognized as dynamic systems that may be far-removed from
      equilibrium. A kinetic approach using the competing ligand exchange method with
      Chelex 100 as the competing ligand and inductively coupled plasmamass
      spectrometry to measure the dissociation kinetics was used to investigate the
      chemical speciation of Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Cd(II), and Pb(II)
      in model solutions of a well-characterized fulvic acid (Laurentian fulvic acid)
      and a freshwater sample collected from the Grand River (Ontario, Canada). The
      kinetic distribution of the metal species were quantitatively characterized by
      their first-order dissociation rate constants. This kinetic speciation approach
      has the advantage of providing an objective method for estimating the
      dissociation rate constants without any a priori assumptions about the number of
      kinetically distinguishable components or the shape of the distribution. Three
      factors were found to influence the kinetics of trace metal competition in the
      freshwater environment: (i) metal-to-ligand ratio, (ii) ionic potential (z2/r),
      and (iii) ligand field stabilization energy. The results illustrate the
      importance of considering the valence-shell electron configuration in predicting
      the kinetics of trace metal competition in the freshwater environment. The
      markedly slow dissociation kinetics of Ni(II) and Cu(II) species suggest that the
      usual equilibrium assumption for freshwaters may not be valid. This study has
      demonstrated the ability of the kinetic model to correctly predict the relative
      rates of trace metal reactions, indicating that the kinetic model provides a
      chemically significant description of the kinetic processes in natural waters.

PMID- 15506190
TI  - Investigation of sorption behavior between pyrene and colloidal organic carbon
      from activated sludge processes.
AB  - The sorption behavior of pyrene for different size fractions of colloidal organic
      carbon (COC) originating from two biological wastewater treatment facilities (a
      full-scale activated sludge system (FSAS) and a membrane bioreactor (MBR)) was
      investigated by fluorescence quenching. Fluorescence lifetime measurements
      demonstrated a dynamic quenching component in all samples, including the
      colloidal-free filtrates. COC sorption coefficients (Kcoc) for pyrene ranged from
      <1 x 10(3) L/kgcoc to 80 x 10(3) L/kgcoc and were comparable to values obtained
      in the literature for natural organic matter. Both linear and nonlinear behaviors
      were observed in the Freundlich-described converted isotherms (n = 0.89-2.1). The
      aromatic content of COC was quantified by the molar extinction coefficient at 280
      nm (e280). Good correlations were observed between COC-pyrene sorption
      coefficients and e280 coefficients, suggesting that e280 may be a useful tool for
      predicting colloidal transport of hydrophobic organic compounds (HOCs) from
      activated sludge systems. The removal of COC from treated effluents may
      appreciably reduce the concentrations of HOCs discharged to receiving streams.

PMID- 15506191
TI  - Chlorination byproduct formation in the presence of humic acid, model nitrogenous
      organic compounds, ammonia, and bromide.
AB  - The formation of trihalomethanes (THMs), haloacetic acids (HAAs), and cyanogen
      halides (CNXs) after chlorination of synthetic solutions containing humic acid,
      nitrogenous organic (N-organic) compounds, ammonia, and bromide ions was studied.
      Humic acid (from Aldrich) was used to provide the source of the precursors.
      Glycine was chosen as the primary model N-organic compound and other four model N
      organic compounds (including glutamic acid, glycylglycine, diethylamine, and
      methylamine) were also evaluated for comparison. The formation of THMs and HAAs
      was found to decrease with increasing glycine and ammonia concentrations but to
      increase with increasing bromide ion concentration. CNX formation was found to be
      highly sensitive to free chlorine to glycine ratios, and its formation trends
      were significantly affected bythe presence/absence of ammonia. The incorporation
      of bromine changed the byproducts speciation toward brominated species and
      enhanced the yields of total THMs, HAAs, and CNXs. Different model N-organic
      compounds exerted different effects on the formation of THMs, HAAs, and CNXs.
      Their effects on the formation of THMs and HAAs were likely dependent on their
      reactivity to chlorine in competing with the humic acid chlorination reactions.
      The difference in the CNCI yields was attributable to the variations in the
      compound structures.

PMID- 15506192
TI  - Stable metal isotopes reveal copper accumulation and loss dynamics in the
      freshwater bivalve Corbicula.
AB  - Characterization of uptake and loss dynamics is critical to understanding risks
      associated with contaminant exposure in aquatic animals. Dynamics are especially
      important in addressing questions such as why coexisting species in nature
      accumulate different levels of a contaminant. Here we manipulated copper (Cu)
      stable isotopic ratios (as an alternative to radioisotopes) to describe for the
      first time Cu dynamics in a freshwater invertebrate, the bivalve Corbicula
      fluminea. In the laboratory, Corbicula uptake and loss rate constants were
      determined from an environmentally realistic waterborne exposure to 65Cu (5.7
      microg L(-1)). That is, we spiked deionized water with Cu that was 99.4% 65Cu.
      Net tracer uptake was detectable after 1 day and strongly evident after 4 days.
      Thus, short-term exposures necessary to determine uptake dynamics are feasible
      with stable isotopes of Cu. In Corbicula, 65Cu depuration was biphasic. An
      unusually low rate constant of loss (0.0038 d(-1)) characterized the slow
      component of efflux, explaining why Corbicula strongly accumulates copper in
      nature. We incorporated our estimates of rate constants for dissolved 65Cu uptake
      and physiological efflux into a bioaccumulation model and showed that dietary
      exposure to Cu is likely an important bioaccumulation pathway for Corbicula.

PMID- 15506193
TI  - Methylmercury and total mercury in plant litter decomposing in upland forests and
      flooded landscapes.
AB  - The overall objectives of this study were to examine the effects of flooding on
      the decomposition and mercury (Hg) content of tissues from plants common to
      boreal upland forests at the Experimental Lakes Area in northwestern Ontario. We
      used litterbags to study changes in total Hg (THg), methyl Hg (MeHg), carbon (C),
      and nitrogen (N) in 12 different plant tissues (birch, alder, blueberry, and
      Labrador tea leaves, bunchberry plants, jack pine needles, Sphagnum spp.,
      Polytrichum spp., and Pleurozium spp. bryophytes, lichen, and fresh and
      extensively decomposed wood) placed on unflooded boreal forest soils and in
      experimentally created reservoirs over an approximately 800 day period. Rates of
      decomposition (as indicated by differences in the percentage of C and N mass left
      in the tissues over time) were slower in plant tissues placed on unflooded soils
      compared to the same tissues that were inundated in reservoirs. Depending on
      tissue type and initial THg concentrations, decomposing litter on both unflooded
      and flooded soils was either a source or a sink for THg. Tissues where initial
      THg concentrations were greater than 30 ng g(-1) represented a source of THg to
      the surrounding environment, whereas tissues that had initial concentrations of
      less than 30 ng g(-1) gained THg mass. Initial rates of change in THg were more
      rapid in plant tissues placed in reservoirs compared to the same plant tissue
      placed on unflooded soils, but there were no differences in final THg masses
      after approximately 800 days. Plant tissues placed in reservoirs exhibited large
      increases in MeHg mass, whereas MeHg mass decreased in the same plants placed on
      unflooded soils. This is the first study examining THg and MeHg cycling in
      decomposing plants in upland boreal forests and reservoirs.

PMID- 15506194
TI  - Investigations of the reactions of monochloramine and dichloramine with selected
      phenols: examination of humic acid models and water contaminants.
AB  - Our paper reports on the reactivities and orientations of two common phenols,
      phenol (2) and m-cresol (3), and some of their chlorinated intermediates with
      aqueous monochloramine, NH2Cl, and dichloramine, NHCl2. We also examined the
      further reactivity of 2,4,6-trichlorophenol (4) with the chloramines. The phenols
      are an important area of investigation because they are substituents in the humic
      acids and are common contaminants in water. m-Cresol (3) was found to be more
      reactive than phenol (2)with both chlorinating agents. Both NH2Cl and NHCl2were
      sufficiently reactive to chlorinate all positions ortho and para to the hydroxyl
      groups. Mono- and dichloramine showed the same orientation with 2 but different
      orientations in their reactions with the substituent phenols. Indophenol (as its
      salt) was formed to a minor extent at high pH but not at pH 9. Both NH2Cl and
      NHCl2 rapidly replaced the parachlorine in 2,4,6-trichlorophenol (4) to give a
      mixture of 2,6-dichloro-1,4-benzoquinone-4-(N-chloro) imine (5) and 2,6-dichloro
      1,4-benzoquinone (18). Similar reactions occurwith 2,4,6-trichloro-m-cresol (17)
      and 2,4,6-trichloro-3-methoxyphenol (29). The products for 17 were confirmed by
      mass spectrometry (El and Cl), 1H NMR, 13C NMR, and IR; the products for 29 were
      confirmed by mass spectrometry (El and Cl) and IR. An ion radical mechanism is
      suggested to account for the chlorine replacement by the chloramines. [No side
      chain oxidation of the methyl group in 17 in H20 or ether occurred, with or
      without ultraviolet radiation.] Both 5 and 18 underwent further chlorination with
      NH2Cl or NHCl2. Imine 5 did not function as a chlorinated agent.

PMID- 15506195
TI  - Using the biotic ligand model for predicting the acute sensitivity of cladoceran
      dominated communities to copper in natural surface waters.
AB  - In this study, the acute copper sensitivity of field-collected cladoceran species
      was determined using their natural surface waters and a standard reconstituted
      test water as test medium. A total of 43 species were collected on two occasions
      from six different sites, representing different water types and chemistries in
      Europe. The collected species belonged to four different families (Daphniidae,
      Bosminidae, Macrothricidae, Chydoridae) and 11 different genera (Daphnia,
      Ctenodaphnia, Ceriodaphnia, Simocephalus, Scapholeberis, Alona, Acroperus,
      Chydorus, Eurycercus, Disparalona, Pleuroxus). In acute experiments with
      immobilization as end point, the 48-h median effective concentrations (48-h EC50)
      for the cladoceran species ranged from 5.30 to 70.6 microg of Cu L(-1) in
      standard test water and from 9.60 to 853 microg of Cu L(-1) in natural waters.
      The mean site sensitivity (the geometric mean of 48-h EC50 values of species
      within a community) ranged from 10.1 to 27.4 microg of Cu L(-1) in standard water
      and from 16.4 to 281 microg of Cu L(-1) in natural water. This indicates that
      bioavailability is more importantthan inter-community (species composition)
      differences in determining the variability of copper toxicity across different
      aquatic systems. For the four surface waters that had a pH within the range for
      which the acute Daphnia magna biotic ligand model (BLM) has previously been
      successfully validated, the BLM predicted 48-h EC50 values for 27 of the 28
      tested cladoceran species within factor of 2 of the observed values. For the same
      sites, all community sensitivities were predicted within a factor of 2.3. The BLM
      was clearly over-protective for the two acidic surface waters tested. Hence, the
      BLM can be considered a valuable tool for estimating the potentially harmful
      effects of copperto natural cladoceran communities, but more research will be
      needed for acidic surface waters.

PMID- 15506196
TI  - Products and mechanism of the reaction of OH radicals with 2,3,4-trimethylpentane
      in the presence of NO.
AB  - Alkanes are important constituents of gasoline fuel and vehicle exhaust, with
      branched alkanes comprising a significant fraction of the total alkanes observed
      in urban areas. Using a relative rate method, a rate constant for the reaction of
      OH radicals with 2,3,4-trimethylpentane of (6.84+/-0.12) x 10(-12) cm3 molecule(
      1) s(-1) at 298+/-2 K was measured, where the indicated error is two least
      squares standard deviations and does not include the uncertainty in the rate
      constant for the n-octane reference compound. Products of the gas-phase reaction
      of OH radicals with 2,3,4-trimethylpentane in the presence of NO at 298+/-2 K and
      atmospheric pressure of air have been investigated using gas chromatography with
      flame ionization detection (GC-FID), combined gas chromatographymass spectrometry
      (GC-MS), and in situ atmospheric pressure ionization tandem mass spectrometry
      (API-MS). Products identified and quantified by GC-FID and GC-MS were (molar
      yields given in parentheses): acetaldehyde (47+/-6%), acetone (76+/-11%), 3
      methyl-2-butanone (41+/-5%), 3-methyl-2-butyl nitrate (1.6+/-0.2%), and 2-propyl
      nitrate (6.2+/-0.8%). These compounds account for 69+/-6% of the reaction
      products, as carbon. Additional products observed by API-MS analyses using
      positive and negative ion modes were C5- and C8-hydroxynitrates and a C8
      hydroxycarbonyl, which, together with the predicted formation of octyl nitrates,
      account for some or all of the remaining products. The product distribution is
      compared to those for the linear and branched C8-alkanes n-octane and 2,2,4
      trimethylpentane.

PMID- 15506197
TI  - Reductive dechlorination of alpha-, beta-, delta-, and gamma
      hexachlorocyclohexane isomers by hydroxocobalamin in the presence of either
      dithiothreitol or titanium(III) citrate as reducing agents.
AB  - The effect of the reducing potential on the reductive dehalogenation of the
      different HCH (hexachlorocyclohexane) isomers has not yet been studied. In the
      present study, the potential for dehalogenation of (alpha-, beta-, delta-, and
      gamma-HCH isomers by the dithiothreitol (DTT) and titanium(III) citrate (reducing
      potential at pH 7, -0.33 and -0.48 V, respectively), with and without the
      addition of hydroxocobalamin was investigated. In the presence of DTT without
      catalyst, there was no disappearance of any of the HCH isomers studied after 1 h
      of treatment. However, disappearance of the gamma- and alpha-HCH isomers was
      observed during the same time period when titanium(III) citrate was used as the
      reductant in the absence of catalyst (62.9 and 16.6% disappearance,
      respectively). Addition of the hydroxocobalamin to the DTT system favored mainly
      the disappearance of gamma- and alpha-HCH (92.9 and 30.8% disappearance after 1
      h, respectively); disappearance of delta-HCH and beta-HCH was small (11.9%) or
      negligible, respectively. Addition of the hydroxocobalamin to the titanium(III)
      citrate system favored the degradation of all HCH isomers under study: beta- and
      alpha-HCH completely disappeared to undetectable levels (<0.1%) after 1 and 2
      min, respectively; degradation of delta-HCH and beta-HCH was slower than that of
      the other two isomers, although they had almost completely disappeared (99.9 and
      99.6% disappearance, respectively) after 10 and 60 min, respectively. The order
      of disappearance, gamma-HCH > alpha-HCH > delta-HCH > beta-HCH, coincided with a
      decreasing order of the axially positioned Cl atoms of these isomers (considering
      their thermodynamically most stable configuration). This study is the first
      description of the rapid degradation of delta- and beta-HCH under abiotic
      conditions, and the results demonstrate the effect of the reducing potential on
      the reductive dehalogenation of HCH isomers.

PMID- 15506198
TI  - Influence of oxidation states on plutonium mobility during long-term transport
      through an unsaturated subsurface environment.
AB  - Lysimeter and laboratory studies were conducted to identify the controlling
      chemical processes influencing Pu(IV) mobility through the vadose zone. A 52-L
      lysimeter containing sediment from the Savannah River Site, South Carolina and
      solid PuIV(NO3)4 was left exposed to natural wetting and drying cycles for 11
      years before the lysimeter sediment was sampled. Pu had traveled 10 cm, with >95%
      of the Pu remaining within 1.25 cm of the source. Laboratory studies showed that
      the sediment quickly reduced Pu(V) to Pu(IV) (the pseudo-first-order reduction
      rate constant, Kobs, was 0.11 h(-1)). Of particular interest was that this same
      sediment could be induced to release very low concentrations of sorbed Pu under
      oxidizing conditions, presumably by oxidation of sorbed Pu(IV) to the more mobile
      Pu(V) species. Transport modeling supported the postulation that Pu oxidation
      occurred in the lysimeter sediment; the inclusion of an oxidation term in the
      model produced simulations that capture the Pu depth profile data. By not
      including the oxidation process in the model, Pu mobility was grossly
      underestimated by a factor of 3.5. It is concluded that both oxidation and
      reduction mechanisms can play an important role in Pu transportthrough the vadose
      zone and should be considered when evaluating disposal of Pu-bearing wastes.

PMID- 15506199
TI  - Identification of copper binding sites in soil organic matter through chemical
      modifications and 13C CP-MAS NMR spectroscopy.
AB  - Metal binding to an organic peat soil was probed by paramagnetic doping with
      copper, chemical modifications of the organic matter in the soil, and 13C CP-MAS
      NMR spin lattice relaxation rate measurements. Carboxyl and hydroxyl functional
      groups were determined to be most significant in copper uptake by the unmodified
      soil. Esterification and acetylation of the soil showed that metal binding by
      carbohydrate structures occurs independently of other functional groups and may
      even induce a pseudochelation phenomenon. Sorption isotherms corroborate the
      importance of carbohydrate structures in metal binding. These results suggest
      that environmental modeling of metal binding and retention in soils should
      incorporate estimates of the distributions of all functional groups in the soil
      organic matter (e.g. aliphatic, carbohydrate, phenolic, carboxyl) and their
      relative binding strengths.

PMID- 15506200
TI  - Formation of secondary organic aerosol by reactive condensation of furandiones,
      aldehydes, and water vapor onto inorganic aerosol seed particles.
AB  - Volatile furandiones and aldehydes are significant atmospheric oxidation products
      of aromatic compounds. The mechanism of secondary organic aerosol formation by
      these compounds was probed using particle chamber observations and macroscale
      simulations of condensed phases. Growth of inorganic seed aerosol was monitored
      in the presence of humidity and high concentrations of 2,5-furandione (maleic
      anhydride), 3-methyl-2,5-furandione (citraconic anhydride), benzaldehyde, and
      trans-cinnamaldehyde. Particle growth commenced when the gas-phase saturation
      level of each organic compound and water vapor (relative to its pure liquid),
      when summed together, reached a threshold near one, implying the formation of a
      nearly ideal mixed organic/aqueous phase. However, these organics are immiscible
      with water at the high mole fractions that would be expected in such a phase.
      Highly acidic dicarboxylic acids produced by the reactions between furandiones
      and water were shown to rapidly acidify an aqueous phase, resulting in greatly
      increased benzaldehyde solubility. Thus, the uptake of these organics onto
      particles in the presence of humidity appears to be reaction-dependent. Finally,
      it is shown that dicarboxylic acids produced in these reactions recyclize back to
      furandiones when subjected to normal GC injector temperatures, which could cause
      large artifacts in gas/particle phase distribution measurements.

PMID- 15506201
TI  - Natural perchlorate has a unique oxygen isotope signature.
AB  - Perchlorate is known to be a minor component of the hyperarid Atacama Desert
      salts, and its origin has long been a subject of speculation. Here we report the
      first measurement of the triple-oxygen isotope ratios (18O/16O and 17O/16O) for
      both man-made perchlorate from commercial sources and natural perchlorate
      extracted from Atacama soils. We found that the delta 18O values (i.e.,
      normalized 18O/ 16O ratios) of man-made perchlorate were at -18.4+/-1.2%, whereas
      natural perchlorate has a variable delta 18O value, ranging from -4.5% to -24.8%.
      The delta 18O and delta 17O values followed the bulk Earth's oxygen isotope
      fractionation line for man-made perchlorate, but all Atacama perchlorates
      deviated from this line, with a distinctly large and positive 170 anomaly ranging
      from +4.2% to +9.6%. These findings provide a tool for the identification and
      forensics of perchlorate contamination in the environment. Additionally, they
      confirm an early speculation that the oxidation of volatile chlorine by 03 and
      the formation of HClO4 can be a sink (albeit a minor one) for atmospheric
      chlorine.

PMID- 15506202
TI  - Interaction of uranyl with calcite in the presence of EDTA.
AB  - Adsorption of uranyl at the surface of calcite was investigated by using batch
      sorption experiments and synchrotron X-ray standing wave (XSW) measurements.
      Aqueous solutions containing 236U(VI) (4.5 x 10(-7) to 1.0 x 10(-4) M) and EDTA
      (5.0 x 10(-7) to 1.1 x 10(-4) M) were reacted for 90 s to 60 min with freshly
      cleaved calcite (104) surfaces and calcite powders. Surface exchange
      coefficients, sorption kinetics, and influence of powder surface area/solution
      volume (SA/V) ratio were investigated by alpha-counting of 236U. Powder sorption
      results at SA/V = 870 cm2/mL fit a Freundlich isotherm [log [U]surface (in
      monolayers) = log K + n log [U]aq (in moles/L)], where K = 1.9+/-0.5 and n =
      0.9+/-0.1, consistent with uptake of U(VI) by a specific surface reaction where
      the availability of sorption sites is nonlimiting in the U concentration range
      measured. Measured U(VI) coverages along this isotherm, based on the calcite
      (104) surface Ca site density, ranged from 0.04% to 5.4% of a monolayer. Steady
      state surface coverages were obtained within 90 s. Sorption of U(VI) on calcite
      (104) single-crystal cleavage surfaces using identical solutions yielded higher
      coverages, because of increased step density induced by dissolution at the
      relatively low SA/V ratio (approximately 1) of these measurements. The
      crystallographic location of the sorbed U(VI) was examined with the synchrotron
      XSW technique. Measurements were performed at the Advanced Photon Source on fresh
      calcite (104) cleavage surfaces reacted for 90 s with U(VI) solutions. Coherent
      fractions for sorbed U ranged from 0.14 to 0.62, and the mean value of the U
      coherent position was 0.84+/-0.02. This position was independent of dissolved
      U(VI) concentration and corresponds to a distance between the U atom and the
      calcite (104) plane of 2.55+/-0.06 A. These results are consistent with U(VI)
      adsorption atthe calcite surface as an inner-sphere uranyl-carbonate surface
      complex bonded with the outer oxygen atom(s) of a single surface carbonate group.
      Steric considerations allow this observed U(VI) surface complex to occur both at
      step sites ((441)_ and (481)_) and on terrace areas adjacent to Ca vacancies.

PMID- 15506203
TI  - Arsenic occurrence, mobility, and retardation in sandstone and dolomite
      formations of the Fox River Valley, Eastern Wisconsin.
AB  - Elevated levels of groundwater arsenic (approximately 100 microg L(-1) = 1.3 x
      10(-6) M) are found in the Fox River Valley, eastern Wisconsin. The goals of this
      study were to identifythe sources of As contamination and to determine the
      reactions responsible for As mobilization and retardation in areas lacking a
      discrete zone of As-enriched sulfides, shown previouslyto cause elevated arsenic
      in groundwater. Detailed mineralogical and chemical analyses were conducted on
      samples from the Sinnipee Group dolomite and St. Peter sandstone in eastern
      Wisconsin. Solution chemistry was monitored in batch reactions of dolomite,
      quartz, and sulfide mineral fractions with a 0.01 M CsCl solution at pH 7 for 3
      weeks in air. Results indicate that arsenic is present in isomorphous
      substitution with pyrite/marcasite (FeS2), which occurs as disseminated veins,
      grains, and nodules in the dolomite and sandstone. The released As subsequently
      sorbs on the ferric oxyhydroxides formed or coprecipitates in a scorodite-like
      phase. Significantly, oxidative dissolution of the disseminated As-rich FeS2
      grains and nodules is sufficient to explain the elevated As levels observed in
      eastern Wisconsin groundwater. Although complete uptake of As is observed in the
      batch experiments, persistent elevated As levels with spatial and temporal
      variations in regional groundwaters are attributed to differences in the type of
      sulfide occurrence (discrete horizon vs dispersed grains, veins, and nodules),
      variations in the dissolved oxygen content of the groundwater, and variable
      (limited) buildup of reacted surface layers on sulfide grains in the natural flow
      through system. Discrete nanoparticulate As phases, As surface precipitates on
      sulfides, and sorbed As on dolomite and quartz are eliminated as major sources,
      and sorption of arsenic on dolomite and quartz is deemed less important than
      association with ferric oxyhydroxides for retardation in the regional system.

PMID- 15506204
TI  - In vivo synchrotron study of thallium speciation and compartmentation in Iberis
      intermedia.
AB  - Thallium (TI) is a metal of great toxicological concern and its prevalence in the
      natural environment has steadily increased as a result of manufacturing and
      combustion practices. Due to its low natural abundance and increasing demand, TI
      is the fourth most expensive metal, thus, recovery and reuse could be a
      profitable endeavor. The hyperaccumulator Iberis intermedia was examined via in
      vivo micro-X-ray absorption near edge (micro-XANES) and micro-X-ray fluorescence
      (micro-XRF) spectroscopies to determine the speciation and distribution of TI
      within leaves of the plant. I. intermedia plants were cultivated under controlled
      conditions in 0, 10, and 20 mg TI kg(-1) soil leading to a shoot concentration of
      up to 13 430 mg TI kg(-1) dry weight plant mass during 10 weeks of growth. Live
      plant leaves were examined by micro-XANES and micro-XRF which determined aqueous
      TI(I) to be the model species distributed primarily throughout the vascular
      network. A direct relationship of vein size to TI concentration was observed. The
      high uptake of TI and high potential biomass of I. intermedia, combined with
      knowledge of TI speciation and compartmentation within the plant, are discussed
      in terms of accumulation/tolerance mechanisms, consequences for potential food
      chain contamination, and phytomining strategies to reclaim TI-contaminated soils,
      sediments, and waters.

PMID- 15506205
TI  - Macroscopic and microscopic observations of particle-facilitated mercury
      transport from New Idria and Sulphur Bank mercury mine tailings.
AB  - Mercury (Hg) release from inoperative Hg mines in the California Coast Range has
      been documented, but little is known about the release and transport mechanisms.
      In this study, tailings from Hg mines located in different geologic settings--New
      Idria (NI), a Si-carbonate Hg deposit, and Sulphur Bank (SB), a hot-spring Hg
      deposit--were characterized, and particle release from these wastes was studied
      in column experiments to (1) investigate the mechanisms of Hg release from NI and
      SB mine wastes, (2) determine the speciation of particle-bound Hg released from
      the mine wastes, and (3) determine the effect of calcinations on Hg release
      processes. The physical and chemical properties of tailings and the colloids
      released from them were determined using chemical analyses, selective chemical
      extractions, XRD, SEM, TEM, and X-ray absorption spectroscopy techniques. The
      total Hg concentration in tailings increased with decreasing particle size in NI
      and SB calcines (roasted ore), but reached a maximum at an intermediate particle
      size in the SB waste rock (unroasted ore). Hg in the tailings exists
      predominantly as low-solubility HgS (cinnabar and metacinnabar), with NI calcines
      having >50% HgS, SB calcines having >89% HgS, and SB waste rock having
      approximately 100% HgS. Leaching experiments with a high-ionic-strength solution
      (0.1 M NaCl) resulted in a rapid but brief release of soluble and particulate Hg.
      Lowering the ionic strength of the leach solution (0.005 M NaCI) resulted in the
      release of colloidal Hg from two of the three mine wastes studied (NI calcines
      and SB waste rock). Colloid-associated Hg accounts for as much as 95% of the Hg
      released during episodic particle release. Colloids generated from the NI
      calcines are produced by a breakup and release mechanism and consist of hematite,
      jarosite/alunite, and Al-Si gel with particle sizes of 10-200 nm. ATEM and XAFS
      analyses indicate that the majority (approximately 78%) of the mercury is present
      in the form of HgS. SB calcines also produced HgS colloids. The colloids
      generated from the SB waste rockwere heterogeneous and varied in composition
      according to the column influent composition. ATEM and XAFS results indicate that
      Hg is entirely in the HgS form. Data from this study identify colloidal HgS as
      the dominant transported form of Hg from these mine waste materials.

PMID- 15506206
TI  - Potential role of chlorination pathways in PCDD/F formation in a municipal waste
      incinerator.
AB  - The role of chlorination reactions in the formation of polychlorinated dibenzo-p
      dioxins (PCDDs) and dibenzofurans (PCDFs) in a municipal waste incinerator was
      assessed by comparing predicted chlorination isomer patterns with incinerator
      flue gas measurements. Complete distributions of PCDD and PCDF congeners were
      obtained from a stoker-type municipal waste incinerator operated under 13 test
      conditions. Samples were collected from the flue gas prior to the gas cleaning
      system. While total PCDD/F yields varied by a factor of 5 to 6, the distributions
      of congeners were similar. A conditional probability model, dependent only on the
      observed distribution of monochlorinated isomers, was developed to predictthe
      distributions of polychlorinated isomers formed by chlorination of dibenzo-p
      dioxin (DD) and dibenzofuran (DF). Agreement between predicted and measured PCDF
      isomer distributions was high for all homologues, supporting the hypothesis that
      DF chlorination can play an important role in the formation of PCDF byproducts.
      The PCDD isomer distributions, on the other hand, did not agree well with model
      predictions, suggesting that DD chlorination was not a dominant PCDD formation
      mechanism at this incinerator. This work demonstrates the use of PCDD/F isomer
      patterns for testing formation mechanism hypotheses, and the findings are
      consistent with those from other municipal waste combustion studies.

PMID- 15506207
TI  - Geostatistical approach for assessing soil volumes requiring remediation:
      validation using lead-polluted soils underlying a former smelting works.
AB  - Assessing the volume of soil requiring remediation and the accuracy of this
      assessment constitutes an essential step in polluted site management. If this
      remediation volume is not properly assessed, misclassification may lead both to
      environmental risks (polluted soils may not be remediated) and financial risks
      (unexpected discovery of polluted soils may generate additional remediation
      costs). To minimize such risks, this paper proposes a geostatistical methodology
      based on stochastic simulations that allows the remediation volume and the
      uncertainty to be assessed using investigation data. The methodology thoroughly
      reproduces the conditions in which the soils are classified and extracted at the
      remediation stage. The validity of the approach is tested by applying it on the
      data collected during the investigation phase of a former lead smelting works and
      by comparing the results with the volume that has actually been remediated. This
      real remediated volume was composed of all the remediation units that were
      classified as polluted after systematic sampling and analysis during clean-up
      stage. The volume estimated from the 75 samples collected during site
      investigation slightly overestimates (5.3% relative error) the remediated volume
      deduced from 212 remediation units. Furthermore, the real volume falls within the
      range of uncertainty predicted using the proposed methodology.

PMID- 15506208
TI  - Toxicity characterization of complex mixtures using biological and chemical
      analysis in preparation for assessment of mixture similarity.
AB  - In the United States, several proposed approaches for using bioassays for the
      risk assessment of complex hazardous mixtures require that selected mixtures be
      "sufficiently similar" to each other. The goal of this research was to evaluate
      the utility of a protocol using in vitro bioassays and chemical analysis as a
      basis for assessing mixture similarity. Two wood preserving wastes (WPWs)
      containing polycyclic aromatic hydrocarbons and pentachlorophenol were extracted
      and fractionated to generate potentially similar mixtures. Chemical analysis was
      conducted using gas chromatography/mass spectrometry. Genotoxicity was evaluated
      using the Salmonella/microsome and Escherichia coli prophage induction assays.
      The crude extract of one WPW was also tested in the chick embryotoxicity
      screening test (CHEST) assay. The CHEST assay provided the most sensitive
      measurement of toxicity. Overall, the biological potency of the samples was not
      well correlated with predicted potency based on chemical analysis. Although
      several mixtures appeared similar based on chemical analysis, the magnitude of
      the response in bioassays was often dissimilar. Fractionation was required to
      detect the genotoxicity of mixture components in vitro. The results confirm the
      need for an integrated protocol, combining chemical analysis, fractionation, and
      biological testing to characterize the risk associated with complex mixtures.

PMID- 15506209
TI  - Azo dye method for mapping relative sediment enzyme activity in situ at precise
      spatial locations.
AB  - Existing methodology for measuring microbial enzyme activity in aquatic sediments
      involves horizontal sectioning of sediment cores into centimeter slices, followed
      by determination of the enzyme activity of each homogenized sediment slice. At
      best, this approach provides only one-dimensional information on the distribution
      of microbial activity. This paper describes the development of a novel technique
      to map sediment enzyme activity in situ at millimeter spatial resolution.
      Naphthol AS enzyme substrates were loaded onto filter membranes by evaporation
      from an organic solvent. The membranes were attached to plastic cards to form
      rigid probes, which were deployed vertically in sediments for a fixed time
      period. The exposed membranes were developed in a diazonium salt solution,
      resulting in the formation of a colored precipitate where substrate hydrolysis
      had occurred. The chromogenic reaction was calibrated and quantified by immersing
      substrate-loaded membranes in a series of solutions of known enzyme activity. A
      flatbed scanner and image analysis software were used to produce digitized images
      and to generate two-dimensional maps of enzyme activity. The technique was used
      to map the spatial features of esterase activity in aquatic sediment samples from
      wetland areas and enabled the precise locations of microbial activity "hotspots"
      to be identified.

PMID- 15506210
TI  - Compensation of the exhaust gas transport dynamics for accurate instantaneous
      emission measurements.
AB  - Instantaneous emission models of vehicles describe the amount of emitted
      pollutants as a function of the driving state of the car. Emission measurements
      of chassis dynamometer tests with high time resolution are necessary for the
      development of such models. However, the dynamics of gas transport in both the
      exhaust system of the car and the measurement line last significantly longer than
      1 s. In a simplified approach, the transport dynamics can be divided into two
      parts: a perfect time delay, corresponding to a piston-like transport of the
      exhaust gas, and a dynamic part, corresponding to the mixing of gases by
      turbulence along the way. This determines the occurrence of emission peaks that
      are longer in time and lower in height at the analyzer than they actually are in
      the vehicle at their location of formation. It is shown here how the sharp
      emission signals at their location of formation can be reconstructed from the
      flattened emission signals recorded at the analyzer by using signal theory
      approaches. A comparison between the reconstructions quality when using the raw
      or the dilution analyzer system is also given.

PMID- 15506211
TI  - Efficient, near-complete removal of DNAPL from three-dimensional, heterogeneous
      porous media using a novel combination of treatment technologies.
AB  - Remediation of porous media containing an entrapped dense nonaqueous phase liquid
      (DNAPL) is extremely difficult due to the heterogeneity and three-dimensional
      spatial nature of typical natural systems. A novel treatment technology based on
      surfactant- and gravity-induced mobilization, dense brine containment and
      collection, and a vapor-phase extraction polishing step is proposed as a means to
      remediate such systems. Laboratory experiments are performed using the suggested
      methodology applied to three-dimensional, heterogeneous systems, which are packed
      based upon a realization from a correlated random field. Entrapped DNAPL is
      effectively removed as a result of each component of the technology. Following
      vapor extraction, less than 1% of the original DNAPL mass remained in the system.
      While these results are very promising, several open issues must be resolved
      before this technology can be considered mature; both the investigation of some
      of these issues and a summary of remaining needs are addressed.

PMID- 15506212
TI  - Chloride effect on TNT degradation by zerovalent iron or zinc during water
      treatment.
AB  - Addition of corrosion promoters, such as sodium and potassium chloride,
      accelerated TNT degradation during water treatment using zerovalent zinc and
      iron. It was theorized that corrosion promoters could be used to accelerate
      electron generation from metallic species, create new reactive sites on the
      surface of metals during contaminated water treatment, and minimize passivating
      effects. The surface area normalized pseudo-first-order rate constant for the
      reaction of zerovalent zinc with TNT in the absence of KCl was 1.364 L x m(-2) x
      h(-1). In the presence of 0.3 mM and 3 mM KCI, the rate constant increased to
      10.5 L x m(-2) x h(-1) and 51.0 L x m(-2) x h(-1), respectively. For the reaction
      with zerovalent iron and TNT, the rate constant increased from 6.5 (L/m2 x h) in
      the absence of KCl to 37 L x m(-2) x h(-1) using 3 mM KCl. The results
      demonstrate that chloride based corrosion promoters enhance the rate of TNT
      degradation. The in-situ breakage of the oxide layer using corrosion promoters
      was applied as a treatment to maintain the long-term activity of the metallic
      species. Zinc maintained a high reactivity toward TNT, and the reactivity of iron
      increased after 5 treatment cycles using 3 mM KCI. Zinc and iron scanning
      electron micrographs indicate that TNT degradation rate enhancement is caused by
      the pitting corrosion mechanism.

PMID- 15506213
TI  - Laboratory assessment of the mobility of nanomaterials in porous media.
AB  - The production of significant quantities of engineered nanomaterials will
      inevitably result in the introduction of these materials to the environment.
      Mobility in a well-defined porous medium was evaluated for eight particulate
      products of nanochemistry to assess their potential for migration in porous media
      such as groundwater aquifers and water treatment plant filters. Contrary to the
      assertion that nanomaterials present monolithic environmental risks, here we show
      that these nanomaterials exhibit widely differing transport behaviors. Fullerene
      based nanomaterials that had been functionalized to facilitate dispersal in water
      displayed the highest mobilities, with a calculated potential to migrate
      approximately 10 m in unfractured sand aquifers. Colloidal aggregates of C60,
      which have been the focus of recent toxicity studies, were among the least mobile
      of the nanomaterials evaluated.

PMID- 15506214
TI  - Potential remediation of waters contaminated with Cr(III), Cu, and Zn by sorption
      on the organic polymeric fraction of olive mill wastewater (polymerin) and its
      derivatives.
AB  - A study on the individual sorption of Cr(III), Cu, and Zn on polymerin, the humic
      acid-like fraction of olive mill wastewater, and its derivatives, K-polymerin and
      an Fe(OH)x-polymerin complex, showed that these heavy metals were strongly sorbed
      on polymerin and K-polymerin in the order Cr(III) > Cu > Zn. The sorption on
      Fe(OH)x-polymerin was to a lower extent compared with that of the other two
      sorbents, but to a higher extent compared with ferrihydride [Fe(OH)x]. Combined
      atomic absorption spectrometry and diffuse reflectance infrared Fourier transform
      spectroscopy analyses showed that the selected heavy metals were individually
      sorbed on polymerin by means of a cation exchange mechanism, which was consistent
      with the replacement of Ca, Mg, K, and H bound to the carboxylate groups of the
      biosorbent and the concomitant chelation of the heavy metals by the OH groups of
      polymerin polysaccharide component. In binary combination and equimolar ratio, Cu
      was sorbed by polymerin more selectively than Zn. In ternary combination and
      equimolar ratio, Cr(III), Cu, and Zn were sorbed by polymerin in the order
      Cr(III) > Cu > Zn. The sorbing capacity of Zn and Cu was strongly influenced by
      Cr(III), whereas the sorbing capacity of Cr(III) was not affected bythe presence
      of the other two metals. The overall sorbing capacity of the binary and ternary
      mixtures of the three metals on polymerin proved to be considerable and much
      greater than that on Fe(OH)x-polymerin. Simulated wastewaters contaminated with
      Cu and Zn were purified after three sorption cycles by polymerin renewed at each
      cycle, whereas those containing a mixture of Cr(III), Cu, and Zn showed residues
      of Zn after five cycles. We briefly discuss environmental and industrial
      advantages for a possible exploitation of polymerin.

PMID- 15506215
TI  - Removal of estrogenic activity and formation of oxidation products during
      ozonation of 17alpha-ethinylestradiol.
AB  - This study investigated the oxidation of the oral contraceptive 17alpha
      ethinylestradiol (EE2) during ozonation. First, the effect of ozone (O3) on the
      estrogenic activity of aqueous solutions of EE2 was studied using a yeast
      estrogen screen (YES). It could be shown that O3 doses typically applied for the
      disinfection of drinking waters were sufficient to reduce estrogenicity by a
      factor of more than 200. However, it proved impossible to completely remove
      estrogenic activity due to the slow reappearance of 0.1-0.2% of the initial EE2
      concentration after ozonation. Second, oxidation products formed during ozonation
      of EE2 were identified with LC-MS/MS and GC/MS and the help of the model
      compounds 5,6,7,8-tetrahydro-2-naphthol (THN) and 1-ethinyl-1-cyclohexanol (ECH),
      which represent the reactive phenolic moiety and the ethinyl group of EE2.
      Additionally, oxidation products of the natural steroid hormones 17beta-estradiol
      (E2) and estrone (E1) were identified. The chemical structures of the oxidation
      products were significantly altered as compared to the parent compounds,
      explaining the diminished estrogenic activity after ozonation. Overall,the
      results demonstrate that ozonation is a promising tool for the control of EE2,
      E2, and E1 in drinking water and wastewater.

PMID- 15506216
TI  - Enhanced bromate control during ozonation: the chlorine-ammonia process.
AB  - Potentially carcinogenic bromate forms during the ozonation of bromide-containing
      waters. Some water treatment facilities have had to use ammonia addition and pH
      depression to minimize bromate formation, but these processes may prove to be
      insufficient to comply with upcoming regulations. The chlorine-ammonia process
      (Cl2-NH3), consisting of prechlorination followed by ammonia addition priorto
      ozonation is shown to cause a 4-fold decrease in bromate formed when compared to
      the ammonia-only process. Experiments revealed three key mechanisms: (i)
      oxidation by HOCl of Br- to HOBr and its subsequent masking by NH3 as NH2Br; (ii)
      decrease of HO- exposure through halogenation of Dissolved Natural Organic Matter
      (DNOM) by HOCI and scavenging of HO by NH2Cl; and (iii) DNOM acting as a bromine
      sink after oxidation of Br- to HOBr. At an ozone exposure of 6 mg/L x min and pH
      8, conventional ozonation of Lake Zurich water spiked with 560 microg/L Br-
      formed 35 microg/L BrO3-, whereas the application of the Cl2-NH3 process resulted
      in 5 microg/L BrO3-. Additional pH depression to pH 6 further decreased bromate
      formation by a factor of 4. Trihalomethanes (THM) and cyanogen chloride (CNCl),
      that mayform during prechlorination and monochloramination, respectively, were
      well below regulatory limits. The chlorine-ammonia process holds strong promise
      for water treatment facilities struggling with a bromate formation problem during
      ozonation.

PMID- 15506217
TI  - Formation of polychlorinated dibenzo-p-dioxins/dibenzofurans from soot of benzene
      and o-dichlorobenzene combustion.
AB  - Soots were prepared from flame combustion of benzene and o-dichlorobenzene
      (ODCB), creating one soot without carbon-chlorine bonds (benzene soot) and one
      with such bonds (ODCB soot). ODCB soot was tested for PCDD/F formation between
      277 and 600 degrees C without additional chlorine, but levels were very low.
      Copper and Cu2O were added as potential catalysts for ODCB soot oxidation, but
      levels of PCDD/F observed were even lower than without these additives. Both
      benzene soot and ODCB soot produced PCDD/F after adding CuCl2 to the reaction
      mixtures, suggesting that a (volatile) metal chloride was needed in order for
      PCDD/F formation to take place. Under the various conditions of [Cu2+], time, and
      temperature tested, ODCB soot was always more reactive than benzene soot in
      forming PCDD/F. It seemed plausible that, despite the fact that CuCl2 was very
      effective in creating C-Cl bonds in benzene soot, the C-Cl bonds created in ODCB
      soot during preparation were of a reactivity so as to make this soot especially
      prone to PCDD/F formation. High temperature (gas phase) chlorination of soots by
      HCI or other chlorinating agents, followed by deposition of these soots and
      condensed metal chlorides on the ducts and walls of the postcombustion zone,
      could create an effective mechanism for de novo formation of PCDD/F.

PMID- 15506218
TI  - Mechanisms of strontium and uranium removal from high-level radioactive waste
      simulant solutions by the sorbent monosodium titanate.
AB  - High-level waste (HLW) is a waste associated with the dissolution of spent
      nuclear fuel for the recovery of weapons-grade material. It is the priority
      problem for the U.S. Department of Energy's Environmental Management Program.
      Current HLW treatment processes at the Savannah River Site (Aiken, SC) include
      the use of monosodium titanate (MST, with a similar stoichiometry to NaTi2O5 x
      xH2O) to concentrate strontium (Sr) and actinides. The high affinity of MST for
      Sr and actinides in HLW solutions rich in Na+ is poorly understood. Mechanistic
      information about the nature of radionuclide uptake will provide insight about
      MST treatment reliability. Our study characterized the morphology of MST and the
      chemistry of sorbed Sr2+ and uranium [U(VI)] as uranyl ion, UO2(2+), on MST,
      which were added (individually) from stock solutions of Sr and 238U(VI) with
      spectroscopic and transmission electron microscopic techniques. The local
      structure of sorbed U varied with loading, but the local structure of Sr did not
      vary with loading. Sorbed Sr exhibited specific adsorption as partially hydrated
      species whereas sorbed U exhibited specific adsorption as monomeric and dimeric
      U(VI)-carbonate complexes. Sorption proved site specific. These differences in
      site specificity and sorption mechanism may account forthe difficulties
      associated with predicting Sr and U loading and removal kinetics using MST.

PMID- 15506219
TI  - Congener-specific dechlorination of dissolved PCBs by microscale and nanoscale
      zerovalent iron in a water/methanol solution.
AB  - Polychlorinated biphenyl (PCB)-contaminated sediments remain a
      significantthreatto humans and aquatic ecosystems. Dredging and disposal is
      costly, so viable in situ technologies to dechlorinate PCBs are needed. This
      study demonstrates that nanoscale zerovalent iron (ZVI) dechlorinates PCBs to
      lower-chlorinated products under ambient conditions, provides insight into
      structure-activity relationships between PCB isomers, and compares the reactivity
      of nanoscale ZVI to that of palladized microscale ZVI. Six PCB congeners were
      studied (22', 34', 234, 22'35', 22'45', and 33'44') to compare the initial rate
      of dechlorination of each and to monitor the order in which chlorines are
      removed. Using 200 g/L of nanoscale ZVI in a 30% MeOH/water mixture, observed
      surface-area-normalized pseudo-first-order PCB dechlorination rate constants
      ranged from 1 x 10(-6) to 5.5 x 10(-4) L yr(-1) m(-2) depending on the PCB
      congener tested. Using 200 g/L of palladized (0.05 wt %) microscale ZVI, surface
      area-normalized pseudo-first-order PCB dechlorination rate constants were
      significantly faster and ranged from 3.8 x 10(-2) to 1.7 x 10(-1) L yr(-1) m(-2),
      but these rates were not sustainable. For nanoscale ZVI, nonorthosubstituted
      congeners had faster initial dechlorination rates than orthosubstituted congeners
      in the same homologue group. Chlorines in the para and meta position were
      predominantly removed over chlorines in the ortho position, which suggests that
      more-toxic coplanar PCB congeners are not likely to form from less-toxic
      noncoplanar, orthosubstituted congeners. Complete dechlorination was not observed
      over the course of the experiments. PCB dechlorination is rapid enough that
      nanoscale ZVI may offer novel in situ remedial alternatives for PCB-contaminated
      sediments.

PMID- 15506220
TI  - Formation of dioxins in the catalytic combustion of chlorobenzene and a
      micropollutant-like mixture on Pt/gamma-Al2O3.
AB  - Catalytic combustion over a 2 wt % Pt/gamma-Al2O3 catalyst of chlorobenzene
      (PhCl) and of a micropollutant-like mixture representative for a primary
      combustion offgas has been investigated. Typical conditions were 1000-1500 ppm of
      organics in the inflow, contact times approximately 0.3 s, 16% O2 in nitrogen at
      approximately 1 bar, and temperature range 200-550 degrees C. PhCl reacts
      considerably slower than when processing Cl-free compounds such as heptane. At
      intermediate temperatures--and incomplete conversion--byproducts are formed,
      especially polychlorobenzenes (PhClx). These are accompanied by polychlorinated
      dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) at levels of about 10(-6)
      relative to PhClx. Additional HCI--made by co-reacting PhCl with tert
      butylchloride--leads to much higher levels of PhClx and PCDD/Fs. Using the
      micropollutant-like mixture, the total chlorine input is reduced almost 20-fold,
      but it nevertheless leads to a 30-fold higher PCDD/F output. This is ascribed to
      reaction of the small amounts of (chloro)phenols in the mixture. The
      congener/isomer patterns of the PCDD/Fs for the mixture and with PhCl per se are
      quite comparable with those found in emissions from incinerators. As carbon is
      not present nor formed on the catalyst surface, de-novo formation therefrom
      cannot be involved. Rather condensation of phenolic entities or like precursors
      must have occurred. Consequences and options to ensure safe application are
      briefly discussed as well.

PMID- 15506221
TI  - Significance of iron(II,III) hydroxycarbonate green rust in arsenic remediation
      using zerovalent iron in laboratory column tests.
AB  - We examined the corrosion products of zerovalent iron used in three column tests
      for removing arsenic from water under dynamic flow conditions. Each column test
      lasted 3-4 months using columns consisting of a 10.3-cm depth of 50:50 (w:w,
      Peerless iron:sand) in the middle and a 10.3cm depth of a sediment from Elizabeth
      City, NC, in both upper and lower portions of the 31-cm-long glass column (2.5 cm
      in diameter). The feeding solutions were 1 mg of As(V) L(-1) + 1 mg of As(III) L(
      1) in 7 mM NaCl + 0.86 mM CaSO4 with or without added phosphate (0.5 or 1 mg of P
      L(-1)) and silicate (10 or 20 mg of Si L(-1)) at pH 6.5. Iron(II,III)
      hydroxycarbonate green rust (or simply, carbonate green rust) and magnetite were
      the major iron corrosion products identified with X-ray diffraction for the
      separated fractions (5 and 1 min sedimentation and residual). The presence of
      carbonate green rust was confirmed by scanning electron microscopy (hexagonal
      morphology) and FTIR-photoacoustic spectroscopy (interlayer carbonate stretching
      mode at 1352-1365 cm(-1)). X-ray photoelectron spectroscopy investigation
      revealed the presence of predominantly As(V) at the surface of corroded iron
      particles despite the fact that the feeding solution in contact with Peerless
      iron contained more As(III) than As(V) as a result of a preferential uptake of
      As(V) over As(III) by the Elizabeth City sediment. Extraction of separated
      corrosion products with 1.0 M HCI showed that from 86 to 96% of the total
      extractable As (6.9-14.6 g kg(-1)) was in the form of As(V) in agreement with the
      XPS results. Combined microscopic and macroscopic wet chemistry results suggest
      that sorbed As(III) was partially oxidized by the carbonate green rust at the
      early stage of iron corrosion. The column experiments suggest that either
      carbonate green rust is kinetically favored or is thermodynamically more stable
      than sulfate green rust in the studied Peerless iron corrosion systems.

PMID- 15506222
TI  - Electrochemical inactivation of triclosan with boron doped diamond film
      electrodes.
AB  - This research investigated an electrochemical method for inactivating
      contaminated stockpiles of the biocidal agent, triclosan. The goal of the
      electrolysis was to produce products that were amenable to treatment in
      conventional activated sludge treatment systems. Triclosan oxidation in
      electrochemical cells with boron doped diamond (BDD) film anodes was investigated
      in aqueous solutions at a pH value of 12. Chronoamperometry experiments showed
      that direct oxidation of triclosan occurred at potentials below those for H2O, Cl
      , or OH- oxidation. Measurable rates of triclosan oxidation began at potentials
      above 0.4 V with respect to the standard hydrogen electrode (SHE), while
      potentials of 0.5, 1.3, and 1.8 V were required to obtain measurable oxidation
      rates of H2O, Cl-, and OH-, respectively. At anode potentials below 2 V, the
      dominant electrode reaction involved direct triclosan oxidation, while indirect
      oxidation was the dominant pathway at higher potentials. However, cyclic
      voltammetry experiments showed that direct oxidation of triclosan resulted in the
      formation of a passivating film on the electrode that could only be removed by
      oxidation at potentials above 3 V. Direct triclosan oxidation showed a very weak
      potential dependence, suggesting that its oxidation was limited by chemical
      dependent factors rather than by an outer-sphere electron transfer reaction.
      Organic triclosan oxidation products consisted primarily of chlorinated acetic
      acids and chlorinated phenolic compounds. Although the byproducts of triclosan
      oxidation became increasingly less reactive with increasing electrolysis time,
      triclosan could be completely oxidized to CO2 at current densities above 2
      mA/cm2. Microtox testing indicated that residual triclosan accounted for nearly
      all the toxicity in the treated water, despite the fact that chlorinated
      byproduct concentrations were significantly higher than those of triclosan
      itself.

PMID- 15506223
TI  - Peroxidase-catalyzed coupling of phenol in the presence of model inorganic and
      organic solid phases.
AB  - Peroxidase-catalyzed oxidative coupling reactions of phenol in aqueous systems
      variously containing silica sand, cellulose, lignin, and polymethylstyrene were
      investigated. These four solid phase materials represent a broad spectrum of
      different natural geosorbent types in terms of their physicochemical
      characteristics. Each solid was found to influence peroxidase-catalyzed phenol
      coupling, either by mitigation of enzyme inactivation, by participation in cross
      coupling, or by a combination of these two activities. Mitigation of enzyme
      inactivation was observed for those three of the four model solids found to
      adsorb the enzyme effectively; i.e., cellulose, silica sand, and lignin. Two
      solids, polymethylstyrene and lignin, were found to participate significantly in
      cross-coupling reactions. It is postulated that relatively hydrophilic solids can
      mitigate peroxidase inactivation by forming enzyme-solid associations. Aromatic
      structures or unsaturated C-C bonds were found to be features of the solid-phase
      materials that allowed them to participate in cross-coupling. The results have
      important implications for process feasibility assessment and the engineering
      design of soil/sediment remediation systems employing enzymatic coupling schemes.

PMID- 15506224
TI  - Degradation of tert-butyl alcohol in dilute aqueous solution by an O3/UV process.
AB  - This paper describes the degradation of tert-butyl alcohol (TBA) in dilute
      aqueous solution by an O3/UV process. The degradation process was investigated
      experimentally in a semi-batch reactor under various operational conditions,
      i.e., ozone gas (O3) dosage, UV light intensity, and water quality in terms of
      varying bicarbonate concentration. TBA was oxidized rapidly in the O3/UV system,
      and acetone, hydroxy-iso-butyraldehyde, and formaldehyde were identified as
      primary intermediates, whereas pyruvaldehyde and acetic, formic, pyruvic, and
      oxalic acids were generated as a result of further oxidation process. A good
      organic carbon balance was obtained, indicating that most reaction intermediates
      have been identified and quantified.

PMID- 15506225
TI  - Chemical structure of arsenic and chromium in CCA-treated wood: implications of
      environmental weathering.
AB  - Chromated copper arsenate (CCA) has been used to treat lumber for over 60 years
      to increase the expected lifetime of CCA-treated wood. Because of the toxicity of
      the arsenic and chromium used in CCA treatment, regulatory and public attention
      has become focused on the potential risks from this exposure source. In
      particular, exposure of children to arsenic from CCA-treated wood used in decks
      and play sets has received considerable attention. X-ray Absorption Spectroscopy
      (XAS) was used to evaluate the chemical structure of As and Cr in three samples
      of CCA-treated materials: newly treated wood, aged wood (5 years as decking), and
      dislodgeable residue from aged (1-4 years as decking) CCA-treated wood. The form
      of the Cr and As in CCA-treated material is the same in fresh and aged samples,
      and between treated wood and dislodged residue. In all cases, the dominant
      oxidation state of the two elements is As(V) and Cr(III), and the local chemical
      environment of the two elements is best represented as a Cr/As cluster consisting
      of a Cr dimer bridged by an As(V) oxyanion. Long-term stability of the As/Cr
      cluster is suggested by its persistence from the new wood through the aged wood
      and the dislodgeable residue.

PMID- 15506226
TI  - Comment on "Environmental assessment of used oil management methods".

PMID- 15506227
TI  - Comment on "A polymer membrane containing Fe0 as a contaminant barrier".

PMID- 15506228
TI  - Father hunger and narcissistic deformation.
AB  - The author advances the hypothesis that paternal availability and the
      relationship between the mother and father are crucial components of evolving
      character structure in children. He proposes that a kind of narcissistic
      pathology featuring perverse sexuality may eventuate in the absence of paternal
      availability and in the presence of a disordered relationship between the
      parents. He also suggests that the ways in which aggression is or is not
      modulated and organized are crucial components of this evolving disorder, and
      that boys are more susceptible to its full manifestation and expression than are
      girls.

PMID- 15506229
TI  - Transcending bitterness and early paternal loss through mourning and forgiveness.
AB  - This paper provides an in-depth account of a clinical path to forgiveness
      following a complicated, delayed mourning of an early loss by a man now entering
      old age. The search for mourning and forgiveness in light of extreme bitterness
      in advancing age is highlighted. Despite the intimate connection between mourning
      and forgiveness, this paper attempts to highlight important differences in their
      dynamics and psychological aims. Forgiveness is conceived as work, unconsciously
      motivated, to safeguard and complement the psychological gains of mourning. The
      distinct features of forgiveness facilitating psychic reorganization, as well as
      the adaptive function of refusal to forgive as a defense against melancholia, are
      discussed. The paper concludes that in this case, the motivation for forgiveness
      was to repair a powerful narcissistic injury.

PMID- 15506230
TI  - To have and to hold: on the experience of having an other.
AB  - This paper reconsiders familiar concepts (such as internalization, object
      representation, and object constancy) in light of the notion of having, in order
      to facilitate creative thinking about how patients are or are not capable of
      experiencing analysts-and how analysts allow them to do so. The meaning of Other
      having is examined from both a theoretical and a subjective point of view. The
      author suggests that the sense of having an Other results from positive real
      experiences, and that the ability to have an Other is the sine qua non, the
      building block, of all mental functions that require empathy.

PMID- 15506231
TI  - Hearing the faith in time: countertransference and religious metaphor in an
      oncology patient's psychotherapy.
AB  - Material from the psychoanalytic psychotherapy of a patient with breast cancer
      demonstrates the emergence of constructive meaning in areas of psychological
      experience burdened by conflicts regarding the dimension of time and faith.
      During analytic work, the spontaneous appearance of religious metaphors revealed
      deeper layers of memory where time, faith, language, and the sense of being
      listened to once interacted in ways whose significance could be conceptualized,
      with the help of the countertransference, as a rediscovery of a hearing breast,
      or even a sacred hearing breast. Implications for the psychoanalysis of religious
      experience are discussed.

PMID- 15506232
TI  - When words fail: psychosomatic illness and the talking cure.
AB  - This paper discusses psychosomatic illness as a disorder of the individual's
      subjectivity in relation, or a surrender of mind and mindfulness to the other.
      Illustrative clinical material highlights the usefulness of Harry Stack
      Sullivan's (I954) detailed inquiry in locating the psychosomatic patient's own
      voice in the consulting room. Particular attention is paid to the form and use of
      language to impede or foster private experience and personal agency.

PMID- 15506233
TI  - A falsifying adolescent.
AB  - The author describes an adolescent patient who, while often speaking factual
      truths, maintained an aura of falsity in her life, and in two interludes of
      psychoanalytic psychotherapy, that functioned as a barrier to psychological
      insight. To match her falsity, the analyst at times modified his functioning as a
      "real" therapist and took on her personification of neglectful and false adults.
      Eventually, the analyst became an object that the adolescent could trust and rely
      on. In discussing the case, the author introduces and applies Bion's ideas
      regarding truth and falsity, and three variations of container-contained
      relationships-symbiotic, commensal, and parasitic-in the context of the case's
      relational perspective.

PMID- 15506234
TI  - Saying the right thing at the right time: a view through the lens of the analytic
      process scales (APS).
AB  - Skillful psychoanalytic technique presumably involves knowing what to say, and
      when and how to say it. Does skillful technique have a positive impact upon the
      patient? The study described in this article relied on ratings by experienced
      psychoanalysts using the Analytic Process Scales (APS), a research instrument for
      assessing recorded psychoanalyses, in order to examine analytic interventions and
      patient productivity (greater understanding, affective engagement in the analytic
      process, and so on). In three analytic cases, the authors found significant
      correlations between core analytic activities (e.g., interpretation of defenses,
      transference, and conflicts) and patient productivity immediately following the
      intervention, but only if it had been skillfully carried out. Findings were
      independently replicated by psychology interns.

PMID- 15506235
TI  - A critical evaluation of Raman spectroscopy for the analysis of lipids: fatty
      acid methyl esters.
AB  - The work presented here is aimed at determining the potential and limitations of
      Raman spectroscopy for fat analysis by carrying out a systematic investigation of
      C4-C24 FAME. These provide a simple, well-characterized set of compounds in which
      the effect of making incremental changes can be studied over a wide range of
      chain lengths and degrees of unsaturation. The effect of temperature on the
      spectra was investigated over much larger ranges than would normally be
      encountered in real analytical measurements. It was found that for liquid FAME
      the best internal standard band was the carbonyl stretching vibration v(C=O),
      whose position is affected by changes in sample chain length and physical state;
      in the samples studied here, it was found to lie between 1729 and 1748 cm(-1).
      Further, molar unsaturation could be correlated with the ratio of the nu(C=O) to
      either nu(C=C) or delta(H-C=) with R2 > 0.995. Chain length was correlated with
      the delta(CH2)tw/v(C=O) ratio, (where "tw" indicates twisting) but separate plots
      for odd- and even-numbered carbon chains were necessary to obtain R2 > 0.99 for
      liquid samples. Combining the odd- and even-numbered carbon chain data in a
      single plot reduced the correlation to R2 = 0.94-0.96, depending on the band
      ratios used. For molal unsaturation the band ratio that correlated linearly with
      unsaturation (R2 > 0.99) was nu(C=C)/delta(CH2)sc (where "sc" indicates
      scissoring). Other band ratios show much more complex behavior with changes in
      chemical and physical structure. This complex behavior results from the fact that
      the bands do not arise from simple vibrations of small, discrete regions of the
      molecules but are due to complex motions of large sections of the FAME so that
      making incremental changes in structure does not necessarily lead to simple
      incremental changes in spectra.

PMID- 15506236
TI  - Dietary intake of essential and long-chain polyunsaturated fatty acids in
      pregnancy.
AB  - The dietary intake of EFA and long-chain PUFA (LCPUFA) by women with (n = 14) and
      without (n = 31) gestational diabetes mellitus (GDM) was determined by repeated
      24-h recalls. Women with GDM consumed significantly more energy as fat compared
      with women who had uncomplicated pregnancies; absolute dietary fat did not
      differ. Dietary n-3 LCPUFA was substantially lower than the current
      recommendation for pregnancy, whereas intake of saturated FA (SFA) exceeded it.
      We conclude that replacing dietary sources of SFA with those of EFA and LCPUFA,
      especially n-3 LCPUFA, would benefit the dietary fat profiles of all pregnant
      women.

PMID- 15506237
TI  - Fatty acid profile and affective dysregulation in irritable bowel syndrome.
AB  - Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder with a
      high co-occurrence with affective dysregulation. Affective disorders have been
      associated with specific changes in the PUFA and cholesterol profile. In IBS,
      similar changes may be present as have been reported in patients with affective
      disorders. This exploratory study investigates (i) the level of affective
      dysregulation (AD) in IBS patients and healthy controls; (ii) PUFA and
      cholesterol profiles in IBS patients compared with controls; and (iii)
      associations between PUFA and cholesterol parameters with the level of AD. Blood
      samples were obtained for determination of the FA composition of plasma
      phospholipids and serum cholesterol in 23 diarrhea-predominant IBS patients and
      23 healthy matched controls. AD was scored using the Symptom Check List
      depression scale, the Hospital Anxiety and Depression Scale, and the Hamilton
      Depression Rating Scale. The level of AD was higher in IBS patients compared with
      controls. PUFA and cholesterol profiles did not differ significantly between
      groups. Total n-3 PUFA and cholesterol were significantly negatively associated
      and the ratio of n-6 to n-3 PUFA and the ratio of arachidonic acid to EPA were
      significantly positively associated with the level of AD. The findings of the
      present study reveal that AD was higher in IBS patients compared with healthy
      controls and that changes in PUFA and cholesterol profiles were significantly
      associated with the level of AD. These results warrant further studies regarding
      the role of PUFA and cholesterol status in the co-occurrence of AD and functional
      gastrointestinal disorders.

PMID- 15506238
TI  - Low concentration of oxidized low density lipoprotein suppresses platelet
      reactivity in vitro: an intracellular study.
AB  - The intracellular mechanisms underlying oxidized low density lipoprotein (oxLDL)
      signaling pathways in platelets remain obscure and findings have been
      controversial. Therefore, we examined the influence of oxLDL in washed human
      platelets. In this study, oxLDL concentration-dependently (20-100 microg/mL)
      inhibited platelet aggregation in human platelets stimulated by collagen (1
      microg/mL) and arachidonic acid (60 microM), but not by thrombin (0.02 U/mL). The
      activity of oxLDL was greater at 24 h in inhibiting platelet aggregation than at
      12 h. At 24 h, oxLDL concentration-dependently inhibited intracellular Ca2+
      mobilization and thromboxane B2 formation in human platelets stimulated by
      collagen. In addition, at 24 h oxLDL (40 and 80 microg/mL) significantly
      increased the formation of cyclic AMP, but not cyclic GMP or nitrate. In an ESR
      study, 24 h-oxLDL (40 microg/mL) markedly reduced the ESR signal intensity of
      hydroxyl radicals (OH(-)) in both collagen (2 microg/mL)-activated platelets and
      Fenton reaction (H2O2 + Fe2+). The inhibitory effect of oxLDL may induce radical
      radical termination reactions by oxLDL-derived lipid radical interactions with
      free radicals (such as hydroxyl radicals) released from activated platelets, with
      a resultant lowering of intracellular Ca2+ mobilization, followed by inhibition
      of thromboxane A2 formation, thereby leading to increased cyclic AMP formation
      and finally inhibited platelet aggregation. This study provides new insights
      concerning the effect of oxLDL in platelet aggregation.

PMID- 15506239
TI  - Effect of a modified milk fat and calcium in purified diets on cholesterol
      metabolism in hamsters.
AB  - Modification of milk fat both by partially replacing saturated FA with oleic acid
      (18:1) and by increasing calcium intake independently reduces plasma cholesterol.
      Whether modification of both factors together would synergistically reduce plasma
      cholesterol is unknown. Seventy-two male golden Syrian hamsters were separated
      into four diet treatment groups (n = 18/group) and fed ad libitum for 7 wk. Diets
      contained either modified milk fat (MMF) or regular milk fat (RMF) with either
      0.5% (MMF and RMF) or 1.3% calcium (w/w) (MMFC and RMFC). All diets contained 11%
      test fat, 4% soybean oil, and 0.15% cholesterol (w/w). During the last week,
      feces were collected for three consecutive days for analysis of fecal FA,
      cholesterol, and calcium excretion. Overnight-fasted animals were sacrificed, and
      plasma and livers were collected for lipid analysis. Neither MMF nor additional
      calcium significantly affected plasma lipids. However, significant interactions
      existed between MMF and additional calcium for the ratio of LDL cholesterol to
      HDL cholesterol (LDL/HDL), indicating that increased calcium intake reduced this
      ratio only in RMF animals. In addition, MMF reduced LDL/HDL relative to RMF. MMF
      significantly increased hepatic total and esterified cholesterol. Additional
      calcium significantly increased fecal calcium and saturated FA (SFA) excretion,
      whereas MMF significantly reduced SFA excretion. RMFC induced the highest
      excretion of 16:0 among all groups. Replacement of SFA with 18:1 in the MMF
      reduced the impact of high calcium on LDL/HDL. Additional calcium reduced LDL/HDL
      only in the presence of RMF, which may be achieved through an increased excretion
      of 16:0.

PMID- 15506240
TI  - Dietary TAG source and level affect performance and lipase expression in larval
      sea bass (Dicentrarchus labrax).
AB  - The influence of dietary TAG source (fish oil, triolein, and coconut oil) and
      level (7.5 and 15% of the diet) on growth, lipase activity, and mRNA level was
      studied in sea bass larvae, from mouth opening until day 24 and from day 37 to
      52. Fish oil and triolein induced better growth in both experiments, this being
      significant at a higher dietary level. Coconut oil significantly decreased growth
      at the higher level, possibly as the result of an excessive supply of medium
      chain TAG. Growth was not related to lipase specific activity, suggesting a
      production in excess to dietary needs. Body lipid content was positively related
      to dietary lipid level and was affected by lipid quality. In addition, larval FA
      composition generally reflected that of the diet. The source of dietary lipid,
      but not the quantity, was shown to affect lipase activity significantly. Coconut
      oil diets induced the highest lipase activity, whereas the effect of fish oil was
      age dependent-it was similar to coconut oil at day 24 but induced the lowest
      lipase activity in 52-d-old larvae. The differential lipase response was probably
      caused by differences in the FA composition of the diet, related to the
      specificity of lipase toward FA differing in chain length and degree of
      saturation. No significant differences were found in lipase/glyceraldehyde-3
      phosphate dehydrogenase mRNA, which suggests the existence of a
      posttranscriptional regulation mechanism.

PMID- 15506241
TI  - Tocotrienol-rich fraction from palm oil affects gene expression in tumors
      resulting from MCF-7 cell inoculation in athymic mice.
AB  - It has recently been shown that tocotrienols are the components of vitamin E
      responsible for inhibiting the growth of human breast cancer cells in vitro,
      through an estrogen-independent mechanism. Although tocotrienols act on cell
      proliferation in a dose-dependent manner and can induce programmed cell death, no
      specific gene regulation has yet been identified. To investigate the molecular
      basis of the effect of tocotrienols, we injected MCF-7 breast cancer cells into
      athymic nude mice. Mice were fed orally with 1 mg/d of tocotrienol-rich fraction
      (TRF) for 20 wk. At end of the 20 wk, there was a significant delay in the onset,
      incidence, and size of the tumors in nude mice supplemented with TRF compared
      with the controls. At autopsy, the tumor tissue was excised and analyzed for gene
      expression by means of a cDNA array technique. Thirty out of 1176 genes were
      significantly affected. Ten genes were downregulated and 20 genes up-regulated
      with respect to untreated animals, and some genes in particular were involved in
      regulating the immune system and its function. The expression of the interferon
      inducible transmembrane protein-1 gene was significantly up-regulated in tumors
      excised from TRF-treated animals compared with control mice. Within the group of
      genes related to the immune system, we also found that the CD59 glycoprotein
      precursor gene was up-regulated. Among the functional class of intracellular
      transducers/effectors/modulators, the c-myc gene was significantly down-regulated
      in tumors by TRF treatment. Our observations indicate that TRF supplementation
      significantly and specifically affects MCF-7 cell response after tumor formation
      in vivo and therefore the host immune function. The observed effect on gene
      expression is possibly exerted independently from the antioxidant activity
      typical of this family of molecules.

PMID- 15506242
TI  - Distribution of tocopherols and tocotrienols to rat ocular tissues after topical
      ophthalmic administration.
AB  - With increasing evidence suggesting the involvement of oxidative stress in
      various disorders and diseases, the role of antioxidants in vivo has received
      much attention. Chemically, tocopherols and tocotrienols are closely related;
      however, it has been observed that they have widely varying degrees of biological
      effectiveness. The present study has been carried out in an attempt to deepen our
      understanding of whether there is a significant difference in distribution
      between tocopherol and tocotrienol homologs to rat eye tissues. Rats were
      administered 5 microL of pure tocopherol or tocotrienol to each eye once a day
      for 4 d. Various tissues of the eyes were separated and analyzed for tocopherol
      and tocotrienol concentrations. The concentration of alpha-to-cotrienol increased
      markedly in every tissue to which it was administered; however, no significant
      increase was observed in the case of alpha-tocopherol. The intraocular
      penetration of gamma-tocopherol and gamma-tocotrienol did not differ
      significantly. Additionally, a significant increase in total vitamin E
      concentration was observed in ocular tissues, including crystalline lens, neural
      retina, and eye cup, with topical administration using a relatively small amount
      (5 microL) of vitamin E, whereas no significant increase was observed when the
      same amount of vitamin E was administered orally. Topical administration of
      tocotrienols is thus an effective way to increase ocular tissue vitamin E
      concentration.

PMID- 15506243
TI  - Oxidation rate of conjugated linoleic acid and conjugated linolenic acid is
      slowed by triacylglycerol esterification and alpha-tocopherol.
AB  - We have recently shown that alpha-eleostearic acid (alpha-ESA), a conjugated
      linolenic acid, has a stronger antitumor effect than conjugated linoleic acid
      (CLA), both in vitro and in vivo. In this study, the oxidative stability of alpha
      ESA was examined compared with linoleic acid (LA), alpha-linolenic acid (LnA),
      and CLA. Thin layers of the FA (LA, 9Z,11 E-CLA, 10E,12Z-CLA, LnA, and alpha-ESA)
      were auto-oxidized at 37 degrees C, and the FA remaining, the absorbed oxygen
      volume, the lipid hydroperoxide content, and the TBARS content were determined.
      The oxidation rate of alpha-ESA was faster than that of the unconjugated FA and
      CLA (9Z, 11 E-CLA and 10E, 12Z-CLA). However, the lipid hydroperoxide and TBARS
      contents following alpha-ESA oxidation were low, suggesting production of only
      small amounts of rapid-reacting secondary oxidation products. Furthermore, the
      oxidative stability of conjugated FA (CLA and CLnA) in which the carboxylic acid
      group was esterified with triacylglycerol was greater than that of the FFA.
      Addition of an antioxidant (alpha-tocopherol) also increased the stability of the
      conjugated FA to a level similar to that of the unconjugated FA.

PMID- 15506244
TI  - Formation of genotoxic dicarbonyl compounds in dietary oils upon oxidation.
AB  - Dietary oils--tuna, salmon, cod liver, soybean, olive, and corn oils--were
      treated with accelerated storage conditions (60 degrees C for 3 and 7 d) and a
      cooking condition (200 degrees C for 1 h). Genotoxic malonaldehyde (MA), glyoxal,
      and methylglyoxal formed in the oils were analyzed by GC. Salmon oil produced the
      greatest amount of MA (1070+/-77.0 ppm of oil) when it was heated at 60 degrees C
      for 7 d. The highest formation of glyoxal was obtained from salmon oil heated at
      60 degrees C for 3 d. More glyoxal was found from salmon and cod liver oils when
      they were heated for 3 d (12.8+/-1.10 and 7.07+/-0.19 ppm, respectively) than for
      7 d (6.70+/-0.08 and 5.94+/-0.38 ppm, respectively), suggesting that glyoxal
      underwent secondary reactions during a prolonged time. The amount of methyglyoxal
      formed ranged from 2.03+/-0.13 (cod liver oil) to 2.89+/-0.11 ppm (tuna oil) in
      the fish oils heated at 60 degrees C for 7 d. Among vegetable oils, only olive
      oil yielded methylglyoxal (0.61+/-0.03 ppm) under accelerated storage conditions.
      When oils were treated under cooking conditions, the aldehydes formed were
      comparable to those formed under accelerated storage conditions. Fish oils
      produced more MA, glyoxal, and methylglyoxal than did vegetable oils because the
      fish oils contained higher levels of long-chain PUFA, such as EPA and DHA, than
      did the vegetable oils. A statistically significant correlation (P < 0.05)
      between the alpha-tocopherol content and the oxidation parameters was obtained
      from only MA and fish oils heated at 60 degrees C for 3 d.

PMID- 15506245
TI  - Fatty acids of the seeds of Origanum onites L. and O. vulgare L.
AB  - Seed oils of Origanum onites L. from the Antalya and Mugla regions and O. vulgare
      L. from the Kirklareli region of Turkey were extracted with hexane in a Soxhlet
      apparatus. The oil yields were 14.1-20.0 and 18.5%, respectively. FA compositions
      of the seed oils were determined by GC and GC/MS. Twenty FA were identified in
      both O. onites and O. vulgare seeds. The major FA of both species were linolenic
      (56.3-57.0%; 61.8%), linoleic (21.5-21.7%; 18.8%), oleic (8.7-8.9%; 5.9%),
      palmitic (5.9-6.5%; 5.5%), stearic (2.1-2.4%; 2.1%), and (Z)-11-octadecenoic (0.6
      0.8%; 0.5%), respectively.

PMID- 15506246
TI  - Effects of hydrocarbon structure on fatty acid, fatty alcohol, and beta-hydroxy
      acid composition in the hydrocarbon-degrading bacterium Marinobacter
      hydrocarbonoclasticus.
AB  - The lipids of the gram-negative bacterium Marinobacter hydrocarbonoclasticus
      grown in a synthetic seawater medium supplemented with various hydrocarbons as
      the sole carbon source were isolated, purified, and their structures determined.
      The hydrocarbons were normal, iso, anteiso, and mid-chain branched alkanes,
      phenylalkanes, cyclohexylalkanes, and a terminal olefin. According to the
      sequential procedure used for lipid extraction, three pools were isolated:
      unbound lipids extracted with organic solvents (corresponding to metabolic lipids
      and to the main part of membrane lipids), OH- labile lipids [mainly ester-bound
      in the lipopolysaccharides (LPS)], and H+ labile lipids (mainly amide-bound in
      the LPS). Each pool contained FA, fatty alcohols, and beta-hydroxy acids. The
      proportions of these lipids in the unbound lipid pools were 84-98%, 1.1-11.6%,
      and 0.1-3.6% (w/w), respectively. The chemical structures of the lipids were
      strongly correlated with those of the hydrocarbons fed; analytical data suggested
      a metabolism essentially through oxidation into primary alcohol, then into FA and
      degradation via the beta-oxidation pathway. Sub-terminal oxidation of the
      hydrocarbon chains, alpha-oxidation of FA or double-bond oxidation in the case of
      the terminal olefin, were minor, although sometimes substantial, routes of
      hydrocarbon degradation. Cyclohexyldodecane did not support growth, likely
      because of the toxicity of cyclohexylacetic acid formed in the oxidation of the
      alkyl side chain. In the OH- and H+ labile lipid pools, beta-hydroxy acids, the
      lipophilic moiety of LPS, generally dominated (28-72% and 64-98%, w/w,
      respectively). The most remarkable feature of these cultures on hydrocarbons was
      the incorporation in LPS of beta-hydroxy acids with Codd, omega-unsaturated, iso,
      or anteiso alkyl chains in addition to the specific beta-hydroxy acid of M.
      hydrocarbonoclasticus, 3-OH-n-12:0. These beta-hydroxy acids were tolerated
      insofar as their geometry and steric hindrance were close to those of the 3-OH-n
      12:0 acid.

PMID- 15506247
TI  - New approach to the analysis of oxidized triacylglycerols in lipoproteins.
AB  - The oxidation of human LDL lipids and the structures of oxidized TAG molecules
      found in LDL were investigated. Pooled samples of 10 normolipidemic and 10
      hyperlipidemic subjects were analyzed. For determination of the oxidation levels,
      the LDL baseline diene conjugation (LDL-BDC) method was used. A method based on
      HPLC and electrospray ionization-MS was optimized and applied to the analysis of
      molecular structures of oxidized TAG in LDL. Differences were found between the
      oxidation levels of the samples. The LDL-BDC value was 22.2 micromol/L serum in
      the normolipidemic group, and 88.1 micromol/L serum in the hyperlipidemic group.
      The amounts of oxidized TAG molecules were small. However, several species of
      oxidized TAG were identified. These included TAG molecules with a keto or an
      epoxy group attached to a FA, and TAG molecules with a FA core aldehyde. In some
      TAG, the keto/epoxy ratio was greater in the hyperlipidemic group compared to the
      normolipidemic group. The results show that our approach is applicable to
      research on lipid oxidation in lipoproteins.

PMID- 15506248
TI  - A paradox and a dilemma.

PMID- 15506249
TI  - A new opportunity for public health development: Athens 2004.

PMID- 15506250
TI  - Mass-casualty terrorist bombings in Istanbul, Turkey, November 2003: report of
      the events and the prehospital emergency response.
AB  - BACKGROUND: This paper describes the two mass-casualty, terrorist attacks that
      occurred in Istanbul, Turkey in November 2003, and the resulting pre-hospital
      emergency response. METHODS: A complex, retrospective, descriptive study was
      performed, using open source reports, interviews, direct measurements of street
      distances, and hospital records from the American Hospital (AH) and Taksim
      Education and Research State Hospital (TERSH) in Istanbul. RESULTS: On 15
      November, improvised explosive devices (IEDs) in trucks were detonated outside
      the Neve Shalom and Beth Israel Synagogues, killing 30 persons and injuring an
      estimated additional 300. Victims were maldistributed to 16 medical facilities.
      For example, AH, a private hospital located six km from both synagogues, received
      69 injured survivors, of which 86% had secondary blast injuries and 13% were
      admitted to the hospital. The TERSH, a government hospital located 1 km from both
      synagogues, received 48 injured survivors. On 20 November, IEDs in trucks were
      detonated outside the Hong Kong Shanghai Banking Corporation (HSBC) headquarters
      and the British Consulate (BC), killing 33 and injuring an estimated additional
      450. Victims were maldistributed to 16 medical facilities. For example, TERSH,
      located 18 km from the HSBC site and 2 km from the the BC received 184 injured
      survivors, of which 93% had secondary blast injuries and 15% were hospitalized.
      The AH, located 9 km from the HSBC site and 6 km from the BC, received 16
      victims. CONCLUSION: The twin suicide truck bombings on 15 and 20 November 2003
      were the two largest terrorist attacks in modern Turkish history, collectively
      killing 63 persons and injuring an estimated 750 others. The vast majority of
      victims had secondary blast injuries, which did not require hospitalization.
      Factors associated with the maldistribution of casualties to medical facilities
      appeared to include the distance from each bombing site, the type of medical
      facility, and the personal preference of injured survivors.

PMID- 15506251
TI  - A comparison of patient needs following two hurricanes.
AB  - OBJECTIVES: The New Mexico-1 Disaster Medical Assistance Team (NM-1 DMAT) has
      responded to more disasters due to hurricanes than disasters from any other type
      of event. To assess whether defined patient needs may be applied to future
      hurricanes, the patient needs after Hurricanes Andrew and Iniki were compared.
      The study question was, "Did patient medical needs differ after these
      hurricanes?" METHODS:  DESIGN: Retrospective cohort review. SUBJECTS: All
      patients evaluated by NM-1 DMAT following Hurricanes Andrew and Iniki.
      OBSERVATIONS: Age, past medical history, chief complaint, diagnosis, diagnostic
      tests, treatments, triage level, and disposition. Age was analyzed using
      Student's t-test, other data were analyzed using the chi-square test. RESULTS: A
      total of 1,056 patients were evaluated. Age distributions did not differ between
      events. More patients had co-morbidities after Hurricane Andrew. The only
      difference in chief complaint was that more patients complained of "cold"
      symptoms following Hurricane Iniki. The only differences in diagnoses were for
      upper respiratory infections, which were diagnosed more often after Hurricane
      Iniki. There were no differences in the administration of tetanus toxoid,
      antibiotics, or analgesics. Patients evaluated after Hurricane Andrew had more
      diagnostic tests performed and a higher illness/injury acuity. The proportion of
      the total number of patients conveyed to a hospital did not differ. CONCLUSION:
      Patient needs were similar after Hurricane Andrew and Hurricane Iniki and may be
      applicable for predicting the needs of patients for future hurricanes.

PMID- 15506252
TI  - Counting crises: US hospital evacuations, 1971-1999.
AB  - OBJECTIVES: To investigate the relative distribution of hazards causing hospital
      evacuations, thereby to provide rudimentary risk information for hospital
      disaster planning. METHODS: Cases of hospital evacuations were retrieved from
      newspaper and publication databases and classified according to hazard type,
      proximate and original cause, duration, and casualties. Both partial and full
      evacuations were included. The total number of evacuation incidents for all
      hazards were compared to the total number of hospital incidents for the one
      hazard, fire, for which national data is available. RESULTS: There were 275
      reported evacuation incidents from 1971-1999, with an annual average of 21 in the
      1990s, the period for which databases were more reliable. The most, 33, were
      recorded in 1994, the year of the Northridge Earthquake. Of all incidents, 63
      (23%) were attributable primarily to internal fire, followed by internal
      hazardous materials (HazMat) events (18%), hurricane (14%), human threat (13%),
      earthquake (9%), external fire (6%), flood (6%), utility failure (5%), and
      external HazMat (4%). CONCLUSIONS: More than 50% of the hospital evacuations
      occurred because of hazards originating in the hospital facility itself or from
      human intruders. While natural disasters were not the preponderant causes of
      evacuations, they caused severe problems when multiple hospitals in the same
      urban area were incapacitated simultaneously. Clearly, as hospitals are
      vulnerable to many hazards, mitigation investments should be assessed not in
      terms of single-hazard risk-cost-benefit analysis, but in terms of capacity to
      mitigate multiple hazards. In view of the many qualifications and limitations of
      the dataset used here, but value of such data for disaster planning, hospitals
      should be asked to submit standardized incident reports to permit national data
      gathering on major disruptions.

PMID- 15506253
TI  - Efficacy of critical incident monitoring for evaluating disaster medical
      readiness and response during the Sydney 2000 Olympic Games.
AB  - INTRODUCTION: Multiple casualty incidents (MCI) are infrequent events for medical
      systems. This renders audit and quality improvement of the medical responses
      difficult. Quality tools and use of such tools for improvement is necessary to
      ensure that the design of medical systems facilitates the best possible response
      to MCI. OBJECTIVE: To describe the utility of incident reporting as a quality
      monitoring and improvement tool during the deployment of medical teams for mass
      gatherings and multiple casualty incidents. METHODS: Voluntary and confidential
      reporting of incidents was provided by members of the disaster medical response
      teams during the period of disaster medical team deployment for the 2000 Sydney
      Olympic Games. Qualitative evaluations were conducted of reported incidents. The
      main outcome measures included the nature of incident and associated contributing
      factors, minimization factors, harm potential, and comparison with the post
      deployment, cold debriefings. RESULTS: A total of 53 incidents were reported.
      Management-based decisions, poor or non-existent protocols, and equipment and
      communication-related issues were the principal contributing factors. Eighty nine
      percent of the incidents were considered preventable. A potential for harm to
      patients and/or team members was documented in 58% of reports, of which 76% were
      likely to cause at least significant harm. Of equipment incidents, personal
      protective equipment (33%), medical equipment (27%), provision of equipment
      (22%), and communication equipment (17%) predominated. Personal protective
      equipment (50%) was reported as the most frequent occupational health and safety
      incident followed by fatigue (25%). Pre-deployment planning was the most
      important factor for future incident impact minimization. CONCLUSIONS: Incident
      monitoring was efficacious as a quality tool in identifying incident contributing
      factors. Incident monitoring allowed for greater systems evaluation. Further
      evaluation of this quality tool within different disaster settings is required.

PMID- 15506254
TI  - Injuries among Afghan refugees: review of evidence.
AB  - BACKGROUND: Injuries are a public health problem in developing countries
      resulting in major financial and productivity losses. Injuries in vulnerable
      populations, such as refugees, make an even greater impact on loss of life.
      Afghan refugees in Pakistan continue to form one of the world's largest refugee
      populations. This study systemically reviews the literature to estimate the
      magnitude and prevalence of intentional and unintentional injuries in Afghan
      refugees, and explores the implications of the findings for refugee healthcare
      policy and development of potential interventions specifically for Afghan
      refugees. METHODS: Electronic databases of MEDLINE, POPLINE, Refworld, and
      Winspirs were searched. In addition, a web search was conducted and specific
      organizational websites were reviewed. The search in developing countries was
      limited to studies in English or with an English abstract for the years 1966
      2001. RESULTS: The literature review identified patients with reported war
      injuries who presented to hospitals. Injuries to extremities (45%) were more
      frequent than injuries to the head or neck (36%, p < 0.001), and thorax/abdomen
      (14%, p < 0.001) regions. A majority of the injuries were caused by explosives,
      which included landmines (32.5%), fragmentations, such as shrapnel (33%), and
      firearms (27%). The mean incidence of mortality in these studies was 11%.
      CONCLUSIONS: Despite such an extensive search, limited information was found
      pertinent to injuries in Afghan refugees residing in refugee camps. This dearth
      of literature on the prevalence of injuries, risk factors, and outcomes among
      this vulnerable group is a research and policy gap for public health. Specific
      quantitive and qualitative studies in this field are required to shape refugee
      healthcare policies and develop intervention programs.

PMID- 15506255
TI  - Civilian exposure to toxic agents: emergency medical response.
AB  - Civilian populations are at risk from exposure to toxic materials as a result of
      accidental or deliberate exposure. In addition to industrial hazards, toxic
      agents designed for use in warfare now are a potential hazard in everyday life
      through terrorist action. Civil emergency medical responders should be able to
      adapt their plans for dealing with casualties from hazardous materials (HazMat)
      to deal with the new threat. Chemical and biological warfare (CBW) and HazMat
      agents can be viewed as a continuous spectrum. Each of these hazards is
      characterized by qualities of toxicity, latency of action, persistency, and
      transmissibility. The incident and medical responses to release of any agent is
      determined by these characteristics. Chemical and biological wardare agents
      usually are classified as weapons of mass destruction, but strictly, they are
      agents of mass injury. The relationship between mass injury and major loss of
      life depends very much on the protection, organization, and emergency care
      provided. Detection of a civil toxic agent release where signs and symptoms in
      casualties may be the first indicator of exposure is different from the military
      situation where intelligence information and tuned detection systems generally
      will be available. It is important that emergency medical care should be given in
      the context of a specific action plan. Within an organized and protected
      perimeter, triage and decontamination (if the agent is persistent) can proceed
      while emergency medical care is provided at the same time. The provision of
      advanced life support (TOXALS) in this zone by protected and trained medical
      responders now is technically feasible using specially designed ventilation
      equipment. Leaving life support until after decontamination may have fatal
      consequences. Casualties from terrorist attacks also may suffer physical as well
      as toxic trauma and the medical response also should be capable of dealing with
      mixed injuries.

PMID- 15506256
TI  - Challenges of major incident management when excess resources are allocated:
      experiences from a mass casualty incident after roof collapse of a military
      command center.
AB  - During a military exercise in northern Norway in March 2000, the snow-laden roof
      of a command center collapsed with 76 persons inside. Twenty-five persons were
      entrapped and/or buried under snow masses. There were three deaths. Seven
      patients had serious injuries, three had moderate injuries, and 16 had minor
      injuries. A military Convalescence Camp that had been set up in a Sports Hall 125
      meters from the scene was reorganized as a causality clearing station. Officers
      from the Convalescence Camp initially organized search and rescue. In all, 417
      persons took part in the rescue work with 36 ambulances, 17 helicopters, three
      ambulance airplanes and one transport plane available. Two ambulances, five
      helicopters and one transport aircraft were used. Four patients were evacuated to
      a civilian hospital and six to a field hospital. The stretcher and treatment
      teams initially could have been more effectively organized. As resources were
      ample, this was a mass casualty, not a disaster. Firm incident command prevented
      the influx of excess resources.

PMID- 15506257
TI  - Media influence on Poison Center call volume after 11 September 2001.

PMID- 15506259
TI  - [Factitious disorder and factitious disorder by proxy].
AB  - Similar to the adult patient, a child or adolescent may actively feign or produce
      artificial symptoms (synonymous: Munchausen syndrome). The more frequent case is
      that the child suffers from being an object of symptom fabrication induced by a
      close person caring for the child, regularly the mother (Munchausen syndrome by
      proxy). This review focuses on psychopathological aspects of the clinically more
      relevant factitious disorder by proxy. Typical behaviour and personality
      characteristics are presented that can be taken as clinical warning signs. Doctor
      mother-interaction is affectively challenging due to conflicting tasks imposed on
      the physician. Complementary to pediatric exclusion of genuine disease,
      psychopathological assessment is required to exclude other sources of deviant
      illness behaviour. Factious disorder shares particular features (active violation
      of the child, false report of history, aggravated symptom presentation and
      increased doctor-hopping, difficulties in conforming maternal report in
      biomedical data) with other psychopathological entities (child abuse, simulation,
      dissociative disorders, somatoform disorders including hypochondria, variants of
      maternal overprotection and infantilization, psychosis or delusion in the
      mother). Criteria for differentiation are presented. Three concepts on the
      psychopathological etiology of factitious disorder by proxy are relevant: In some
      cases, it may be conceived as secondary manifestation of a primary
      psychopathological entity or personality disorder. Learning theory emphasises
      operant rewards received from vicarious sick role. Attachment theory provides
      possible explanations concerning the traumatic impact on the child, early sources
      of psychopathology in the fabricating mother and risks for intergenerational
      transmission of factitious disorders.

PMID- 15506258
TI  - International standards and guidelines on education and training for the multi
      disciplinary health response to major events that threaten the health status of a
      community.
AB  - The 13th World Congress on Disaster and Emergency Medicine, convened in
      Melbourne, Australia in May 2003, requested the World Association for Disaster
      and Emergency Medicine (WADEM) to lead the development of "International
      Standards and Guidelines on Education and Training for "Disaster Medicine". This
      Paper has been developed by a Working Group of the WADEM Education Committee
      ("the Working Group") in response to that request from the international
      "Disaster Medicine" and emergency health community. The main focus of the Working
      Group is to develop standards and guidelines for education and training in the
      multi-disciplinary health response to major events that threaten the health
      status of a community. The contemporary view is that of a multi-disciplinary
      health response to major events which threaten the health status of a community,
      including the prevention and mitigation of future events, and taking account of
      the broader context in which these events occur. It is the vision of the Working
      Group that evidence-based standards and guidelines for education and training
      must be developed in a broad sense, for all members of the healthcare community.
      Rather than purely describing isolated performance indicators, the Working Group
      agreed that priority be given to explaining the general approach, presenting the
      conceptual framework, clarifying important principles, and describing the
      educational needs and training requirements for situations for which there exist
      a major threat to the health status of a community. It is not the intent to
      produce an updated educational curriculum for special courses in "Disaster
      Medicine" by listing levels of theoretical knowledge and clinical skills required
      for medical doctors, nurses, and paramedics. Nor, does the Working Group think it
      is useful to repeat requirements and learning outcomes that are part of the
      normal basic education and training for the various health professionals. The
      purpose of this Issues Paper is to present an initial summary of current issues
      relating to an international perspective of "Disaster Medicine" education and
      training. This summary has been prepared following discussions within the Working
      Group of the WADEM Education Committee. The paper aims to stimulate debate and
      form the basis of further of discussion at an international meeting scheduled to
      be held in Brussels (Belgium) on 29-31 October 2004. The Working Group has
      structured this Issues Paper into five parts and has identified several key
      issues for discussion. Part 1: Understanding the contemporary interpretation of
      the multi-disciplinary health response to major events that threaten the health
      status of a community. Issue 1: Definitions and terminology in "Disaster
      Medicine"; Issue 2: Getting to grips with the contemporary concepts and
      international trends in 'Disaster Medicine"; and, Issue 3: Valuing personal
      attributes in "Disaster Medicine" practitioners. Part 2: Developing an underlying
      scientific framework for linking theory to practice in "Disaster Medicine". Issue
      4: Creating a scientific framework(s) for "Disaster Medicine". Part 3: Defining a
      conceptual framework and general principals to develop "International Standards
      and Guidelines on Education and Training for the Multi-disciplinary Health
      Response to Major Events that Threaten the Health Status of a Community". Issue
      5.: Where are we now? Getting to grips with the contemporary concepts and
      international trends in "Disaster Medicine" education and training. Issue 6:
      Where do we want to get to? Identifying contemporary, evidence-based education
      and training standards and guidelines for 'Disaster Medicine" education and
      training programs. Issue 7: How do we get there? Overcoming barriers to
      introducing the International Standards and Guidelines. Part 4: Maintaining the
      momentum--improving international collaboration. Issue 8: Exploring the
      feasibility of an ongoing, international, collaborative network of "Centres of
      Excellence" in "Disaster Medicine" research and/or education. Part 5: Additional
      input. Issue 9: What other issues would you like to bring to the attention of the
      Working Group? CONCLUSIONS: The results of the consultation will lead to the
      development of international standards and guidelines that will be presented and
      consensus sought during the 14th World Congress on Disaster and Emergency
      Medicine (WCDEM-14) to be convened in Edinburgh in May, 2005.

PMID- 15506260
TI  - [Humor as an additional component of psychological and psychiatric diagnostics in
      children and adolescents: concept of a humor-diagnostic model].
AB  - When looking at humor of children and adolescents from a diagnostic point of
      view, there exist additional diagnostic possibilities other than the usual
      assessment methods from child and adolescent psychiatry or psychology.
      Spontaneous humorous behavior in everyday life and a humorous performance during
      assessment situations of children can provide a useful basis for further
      diagnostic considerations. From a developmental point of view it is important to
      notice what kinds of humor a child is already capable of understanding and of
      performing towards others. Whilst the actual readiness for cheerfulness contains
      information concerning the emotional state, the more general readiness for being
      cheerful renders insight into basic parameters of temperament. To what extent a
      child uses humor either supportively or destructively, contains information about
      psychodynamic connections, motivational aspects and active coping strategies.
      Concerning the diagnostic approach, reports of parents as well as humor tests or
      hypothesizing methods (e.g. humorous drawings) can be used. Central in using
      humor as a diagnostic assessment device is the knowledge of humor development and
      of the relations between psychiatric illnesses and humor.

PMID- 15506261
TI  - [Norm values for the questionnaire to assess the own body (Fragebogen zur
      Beurteilung des eigenen Korpers, FBeK) for adolescents].
AB  - Body experience is of special importance during adolescence. The questionnaire to
      assess the own body (Fragebogen zur Beurteilung des eigenen Korpers) is one of
      the most frequently used German questionnaires in the field of body experience.
      The aim of the study is to test the application of the questionnaire in the age
      range of adolescence and to provide norm values. A sample of 346 adolescents
      between 12 and 20 years was tested. With the exception of three items which
      concern sexuality the questionnaire was well applicable in this age group. Gender
      differences among adolescents are more pronounced than among adults. Girls
      compared to boys showed higher mean values in the scales unsecurity and
      accentuation of the own body, while the mean values were lower in the scale
      attractivity/self esteem. Norm values are derived separately for boys and girls.

PMID- 15506262
TI  - ["... so that Theo knows what he should do better". Client orientation in social
      therapeutic child group work--an experiential report of quality management at a
      child guidance clinic].
AB  - Within the framework of internal evaluation and self-evaluation activities in a
      child guidance clinic, measures of success have to date been based primarily on
      the degree to which the delegating organisations are satisfied with the results
      of the counselling. The orientation of the success of counselling towards the
      results stems from the fact that the process of helping is not generally manifest
      to parents, schools, and education staff. It takes place in the context of direct
      contact between therapists and children, the immediate addresses of help, and
      therefore often remains "hidden". Since the children's perspective--their
      impressions and appraisals--has often been neglected in past assessment methods,
      it hardly plays any role at all in the discussion of quality at counselling
      centres. This made it all the more stimulating for all those involved to initiate
      improvement measures within the framework of quality management on the basis of a
      client survey and in this way to launch a shared learning process as to how
      client orientation can flow directly into everyday practice. This is certainly
      the first attempt of its kind in the work of child guidance clinics to develop an
      understanding of client orientation in line with the expectations of parents and
      children and to link this to the quality development of the service. In the first
      part of this experiential report, the external process coach provides a brief
      summary of the assessment method employed in connection with the introduction of
      internal quality management at the counselling centre. This is followed by the
      centre's own description of the concrete performance of the client survey with
      children using the example of social-therapeutic child group work. The study
      concludes with a discussion of the benefit drawn from this process for the
      improvement of this pedagogical project.

PMID- 15506263
TI  - Employment-based retirement plan participation: geographic differences and
      trends.

PMID- 15506264
TI  - [Risk factors and carotid atherosclerosis in patients with transient ischaemic
      attack].
AB  - In order to identify association between serum lipid levels, hypertension,
      smoking, diabetes and the severity of carotid atherosclerosis, ultrasonography of
      extracranial arteries was performed in 56 male patients (age: x = 62.9 years,
      S.D.= 9.4) with transient ischaemic attack. According to color Doppler criteria,
      patients were divided into two groups--Group I: < 50%, Group II: > or = 50%
      stenosis of the carotid artery. In Group I, there were 36 (64.3%), and in Group
      II 20 (35.7%) patients. No significant differences between those two groups were
      found regarding mean levels of total cholesterol, LDL- and HDL-cholesterol, and
      triglycerides (normolipemic levels were found in both groups). Two groups were
      compared also concerning the incidence of hypertension, diabetes and smoking, and
      no significant difference was found, as well. Stepwise multiple logistic
      regression analysis revealed that only age significantly increased the risk of
      severe carotid atherosclerosis (odds ratio 2.0, 95% CI: 1-4.3). These results
      show the influence of age in pathogenesis of carotid atherosclerosis.

PMID- 15506265
TI  - [The proportion of non-invasive (Tis) and minimal invasive cancers (T1a,b) among
      breast cancer in Split region].
AB  - As a result of the use of screening mammography and the introduction of programs
      for early detection of breast cancers, many breast biopsies are now performed for
      small, non-palpable, mammographically detected abnormalities. In contrast to
      breast biopsies in the premammographic era, breast biopsies for mammographic
      abnormalities contain a greater number of minimal invasive breast cancers
      (T1a,b), non-invasive-in situ cancers (Tis), and histological types of breast
      cancers with excellent prognosis. The aim of this study was to estimate the basic
      histopathologic features of breast cancers in Split region, with emphasis on in
      situ and minimal invasive cancers. The results of this study are achieved by
      analysis of pathohistologic characteristics of 937 breast cancers surgically
      removed in Split Clinical Hospital in the five year period (1997-2001), detected
      in population without early breast cancer detection programs. The proportion of
      minimal invasive cancers (T1a,b) and in situ cancers (Tis) was 15.16% and 2.78%,
      respectively. Axillary nodal metastases (N1) occurred in 42.9% of patients of the
      whole group, and in the group of minimal invasive cancers nodal metastases
      occurred in 14.78% of cases. The small percentage of T1a,b and Tis cases of
      breast cancers in Split region suggests the necessity for introduction of breast
      cancer early detection programs, with the emphasis on screening mammography
      programs in a part of female population.

PMID- 15506266
TI  - [Hypersensitivity to pollen of Olea europea in patients with pollen allergy in
      the area of Zadar and Dubrovnik].
AB  - Olive pollen is one of the most important causes of inhalant allergy in countries
      around the Mediterranean sea. Due to the lack of information on hypersensitivity
      to the pollen of Olea europea from Croatian coast, the aim of this investigation
      was to establish the frequency of hypersensitivity to the pollen of Olea europea
      in pollen allergic patients in Zadar and Dubrovnik. Also, we compared two areas
      of Dalmatia regarding the number of patients and expression of allergy to the
      Olea europea. A total of 810 patients, children and adults, with pollen allergy
      were examined in both areas, Zadar and Dubrovnik. In the area of Zadar we
      examined 546 participants and in the area of Dubrovnik 264 participants. The
      patients were assessed by anamnestic data, clinical examination, measurement of
      pulmonary function (adults and children older than 7 years), skin prick test and
      enzymo-immunologic UniCAP test for measurements of specific IgE antibodies. For
      statistical analysis we used chi square test. Hypersensitivity to the allergy of
      Olea europea occurred in 66/810 (8.15%) assessed participants with pollen
      allergy. The comparison between the two areas didn't show any statistical
      difference in the number of affected participants with hypersensitivity to the
      Olea europea. Also, we didn't show any statistical difference in comparison of
      skin prick tests, immunologic measurements of specific IgE antibodies, or
      clinical manifestations between participants in the two investigated areas. The
      most prevalent clinical manifestation was rhinitis registered in 39/66 (59%)
      patients with hypersensitivity to the olive pollen. The majority of patients with
      hypersensitivity to olive pollen 51/66 (77%) live in towns. Only 3/66 (4%)
      participants live on an island. Rhinitis was the most prevalent clinical
      manifestation in our patients with hypersensitivity to allergen of Olea europea.
      Hypersensitivity to olive pollen was higher in participants who lived in towns.
      The hypersensitivity to Olea europea didn't show any difference between the two
      investigated areas of Dalmatia.

PMID- 15506267
TI  - [Congenital penile curvature (chordee without hypospadias): surgical treatment
      for correction of penile curvature and/or buccal mucosal graft urethroplasty].
AB  - Presented are the cases of 19 boys with ventral penile curvature without
      hypospadias. The cases were categorised into three groups according to the
      severity of the anomaly. In group I were 7 boys with ventral penile curvature
      affecting the shortening of the frenulum with skin tethering. The anomaly was
      corrected by fraenulotomy and, in 4 boys, by ventral "V" and "Y" penile
      skinplasty with excellent cosmetic results. In group II were 10 boys with an
      evident chordee. In 4 boys, the chordee was of type III according to Devin
      Horton. A chordectomy was done with a "V" and "Y" skinplasty with very good
      result. The remaining 6 cases were chordee type II according to D-H. The same
      treatment was undertaken here, but with an additional Nesbit's dorsal tunica
      albuginea plication in 4 boys and a 50% success (3 of 6). In group III were 5
      boys, 3 previously failed chordectomy from group II and 2 with "skin urethra"
      type chordee I according to D-H. All boys in this group were treated for
      urethroplasty with autologous buccal mucosal graft. Good results were obtained in
      3 of 5 (60%). Successful outcome was achieved in both cases with "skin urethra"
      not previously treated. The results of our urethroplasty with buccal mucosa agree
      with those in literature. In the treatment of chordee without hypospadias, where
      it was necessary to reconstruct the urethra there was a constant problem of the
      shortage of local tissue, so we believe that buccal mucosa is a good choice.

PMID- 15506268
TI  - [Osteoporosis in men].
AB  - Male osteoporosis represents an important public health problem. According to
      NHANES III (National Health and Nutrition Examination Survey), 7% of white men
      aged 50 years and over have osteoporosis. One-third of all hip fractures occurred
      in men and prevalence of death after hip fracture is twice as high as in women.
      Hypogonadism, alcohol abuse and glucocorticoid excess are the most frequent
      causes of secondary osteoporosis in men, while in 30-50% of cases osteoporosis is
      idiopathic. In the article we discuss etiology, epidemiology, diagnostic
      procedure and treatment of osteoporosis in men.

PMID- 15506269
TI  - [Nitric oxide--an important signalling molecule in normal and pathological
      pregnancy].
AB  - The numerous studies on the multifunctional nature of the nitric oxide (NO) have
      suggested the wide variety of functions mediated by this molecule in vital
      processes in cardiovascular, nervous, gastrointestinal, urogenital system and
      during immunological reactions. In this review we present the results of
      experiments carried out on animal models, as well as the results of clinical
      studies considering the role of NO and its metabolites during pregnancy and
      delivery. During pregnancy NO is one of the most important relaxing factors of
      myometrium, and also no less important in the control of blood flow in uterus and
      placenta. Changes in NO production at the end of pregnancy could be important for
      the beginning of delivery and cervical maturation. Also it seems, and our
      preliminary results as well as results of other investigators suggest, that
      higher levels of NO are produced during some pathological conditions in pregnant
      women, e.g. IUGR, preeclampsia, preterm delivery. The implications of NO donors
      or inhibitors of NO synthesis used in therapy of previously mentioned conditions
      will be also discussed.

PMID- 15506270
TI  - [Ethics and organ transplantation].
AB  - Organ transplantation becomes an accepted method of treatment, being closely
      accompanied with the development of transplantation ethics. Numerous problems and
      dilemmas occurring in this process can be grouped as problems connected with
      confirming death, and ethic dilemmas connected with obtaining and distributing
      organs. An attempt to overcome a chronic great lack of cadaver donors is made by
      various creative attitudes that can be applied only if they fulfill ethical
      criteria. A difficult question of just organ distribution causes many ethical
      dilemmas. Solution should be sought in the multidisciplinary approach of
      bioethics with medicine, politics, legislature and sociology.

PMID- 15506271
TI  - ["De re publica otorhinolaryngologica].
AB  - "De re publica otorhinolaryngologica" is the title of the article by Ante Sercer
      published in Lijecnicki vjesnik in 1941, five years after the moving of the Ear,
      Nose and Throat Department to Salata. In this paper he elaborated his conception
      of a modern ENT department, and presented what had been done in this regard.
      Professor Dragutin Masek had a special merit in founding the Department in 1921,
      and stayed at its head till 1929. His successor prompted its moving from the
      building of elementary school in Draskoviceva Street to Salata, where other
      departments of the School of Medicine in Zagreb were situated. At the beginning
      of the 20th century, the issue of the construction of a territorial hospital
      which would serve as the University Hospital of the future School of Medicine
      emerged. Our ancestors showed great enthusiasm in overcoming the obstacles to the
      construction of the University Hospital in Salata. We chose only a small number
      of important facts by which we tried to demonstrate of the Department in the
      period in which the heads after D. Masek and A. Sercer were Branimir Gusic and
      Zvonimir Krajina. The most important current activities of the Department are
      further briefly described. Although the Department developed the programs which
      naturally follow from the respectable history, in agreement with creative
      potentials of its employees, and professional and scientific standards within the
      European Union, for the third time in the modem history we had to resists the
      unacceptable moving into restricted and unfavorable settings at the other
      location. Recently, plans of building the "eastern comb" on Rebro, and the moving
      of the Department to Rebro, have been offered. On several occasions the council
      of our Department gave negative evaluation of these plans and suggested solutions
      when the project became available "post hoc". Modest investments at the present
      location would provide the Department with a part of necessary conditions for
      further continuing development, appropriate to its impressive historical
      development and current value in Croatian, European and world
      otorhinolaryngology. It is well known that only the experts in a profession know
      the specific determinants and developmental requirements in their field. By
      defending its rights and duty to influence the design of developmental directions
      of the specialty, the Department has also today shown that it is worthy its past.

PMID- 15506272
TI  - [On sudden infant death syndrome in the Republic of Croatia].

PMID- 15506273
TI  - [Prostatic lithiasis].

PMID- 15506274
TI  - [Comparative study on the original plant differences of Chinese traditional
      medicines and Japanese Kampo medicines].
AB  - Based on the Chinese pharmacopeia 2000 ed and Japanese pharmacopeia 14st ed., the
      original plant differencesof Chinese raditional medicines and Japanese Kampo
      medicines were compared by making list. The differences and reasons were
      analyzed.

PMID- 15506275
TI  - [Present situation and prospects of special fertilizer for traditional Chinese
      medicine herbs].
AB  - OBJECTIVE: To find out the present situation and the development trend special
      fertilizer of the traditional Chinese medicina plants. METHOD: By consulting a
      great deal of literatures on special fertilizer and fertilization on traditional
      Chinese medicine herbs, and based on the scientific research and manufacture
      experience of the author, and the theoretic actuality of the researches on the
      fertilization of traditional Chinese medicine herbs, the present study of the
      special fertilizer inside and outside of our country was analyzed. CONCLUSION:
      The view points of developing special fertilizer for Chinese traditional medicine
      were put forward, and the development trend of special fertilizer for traditional
      Chinese medicine herbs was forecasted.

PMID- 15506276
TI  - [Pressurized solvent extraction in quality control of Chinese herb].
AB  - Pressurized solvent extraction (PSE) is a new extraction technology which has
      been developed in recent years and widely used as sample analysis in
      environmental, food and pharmaceutical fields. Extraction technique is a key
      technology in quality control of Chinese herb. Conventional extraction techniques
      have been a bottleneck of blocking the development of quality control of Chinese
      herb. This article attempts to review the basic principle, methods, apparatus and
      main characteristics of PSE and its applications to quality control of Chinese
      herb.

PMID- 15506277
TI  - [Study on genetic diversity of herba Cistanches by RAPD].
AB  - OBJECTIVE: To determine the genetic diversity of Cistanche species. METHOD: Two
      populations of Cistanche deserticola and four populations of C. tubulosa were
      analyzed by random amplified polymorphic DNA (RAPD) markers. RESULT: A total of
      76 and 87 loci were amplified using 10 random primers each other. The average
      percentage of polymorphic loci of C. deserticola was 47.37%. The PPL were 39.47%
      and 35.53% for two populations. Average Nei's gene diversity was 0.1358, Shannon'
      s genetic diversity was 0.2072, and Gst was 0.2546. The average PPL of C.
      tubulosa was 27.59%. It was 19.54% to 25.29% in different populations and Andi'er
      population had the highest. Average Nei's gene diversity was 0.0823, and Shannon'
      s genetic diversity was 0.125 8, Cst was 0.175 5. CONCLUSION: The diversity of
      Cistanche deserticola is higher than that of C. tubulosa, but both has
      differentiation among populations, C. deserticola has already separated itself
      into two different ecotypes.

PMID- 15506278
TI  - [Occurrence and control of pests about Cistanche deserticola and its hosts].
AB  - OBJECTIVE: To investigate the kinds and occurrence of pests of Cistanche
      deserticola and its hosts so as to find ways of pest control. METHOD: Pests of C.
      deserticola and its hosts were investigated in Xinjiang, Inner Mongolia and
      Ningxia where C. deserticola grows, the occurrence of Anomala titanis Reitter was
      investigated in the field, and phoxim was used for field control. RESULT: There
      are 17 kinds of pests which harm C. deserticola and its hosts. Phoxim 40% EC 1000
      times, 2000 times and Phoxim 3% GR [8 kg x (667 m2)(-1)] had 100% controlling
      effect, and 3% GR [4 kg x (667 m)(-2-1)] had 88.23% controlling effect.
      CONCLUSION: Many kinds of pests can harm the C. deserticola and its hosts. Phoxim
      is good for killing A. titanis Reitter.

PMID- 15506279
TI  - [Influence of gentian leaf blight on the output and quality of Chinese gentian].
AB  - OBJECTIVE: To study the influecnce of gentian leaf blight on the output and
      quality of rough gentian. METHOD: The same grade seedlings were transplanted,
      disease of every plant was investigated in autumn and the output of gentian was
      determined. HPLC was applied to determine the content of gentiopicroside and
      swertiamarin. RESULT: The output decreased with the aggravation of the disease,
      and the decrease was obvious when the index of disease was above 60. The content
      of gentiopicroside and swertiamarin began to drop when the index of disease was
      above 70. CONCLUSION: The loss of output and the drop of quality are relatively
      heavy when the disease is serious. The loss of income is not obvious when the
      index of disease is under 60.

PMID- 15506280
TI  - [Study on extraction technology for extract and flavonoids in Chrysanthemum
      morifolium by orthogonal design].
AB  - OBJECTIVE: To ascertain extraction technology condition for extract and
      flavonoids from Chrysanthum morifoliwn. METHOD: The optimizing ultrasonic
      extraction condition on the basis of extractive yield and flavonoids were
      determined by orthogonal design. RESULT: The order of factors which affected the
      flavonoid extraction was extraction times > ethanol concentration > ultrasonic
      time > solvent quantity. CONCLUSION: The optimum ultrasonic extractions are
      A2B3C3D3. Compared with traditional extraction, ultraction method is timesaving,
      simple to operate, stable and need not be heated.

PMID- 15506281
TI  - [Determination of constant for the inclusion complex of Yinqiao volatile oil with
      beta-cyclodextrin].
AB  - OBJECTIVE: To determine the constant for the inclusion complex of Yinqiao
      volatile oil with beta-cyclodextrin. METHOD: The stability constant for the
      inclusion complex of Yinqiao the volatile oil with beta-cyclodextrin was
      detemined under multiwavelength by ultraviolet spectroscopy, and spectroscopy
      feature for inclusion complex was studied. The phase solubility-curve showed the
      inclusion proportion. The inclusion complex of Yinqiao the volatile oil with beta
      cyclodextrin was prepared by saturated aqueous solution. The DTA spectroscopy of
      inclusion complex was different from not only oil with beta-cyclodextrin but also
      the mixture of them. RESULT: The inclusion complex of Yinqiao the volatile oil
      with beta-cyclodextrin was formed. The experimental data of inclusion complex
      fitted well to the molar ratio of 1:1. There was good liner feature under
      multiwavelength of ultraviolet spectroscopy. CONCLUSION: Adopting multiwavelength
      method may determine the appearant stability constant of multicomponential
      traditional drug. The determination of the stability constant of the inclusion
      complex can be used in traditional drug.

PMID- 15506282
TI  - [Studies on extraction process of Fructus Schisandrae chinensis and Fructus
      Ligustri lucidi in gandening tablet].
AB  - OBJECTIVE: To optimize the combined extraction methods of Fructus Schisandrae
      Chinensis and Fructus Ligustri Lucidi. METHOD: The extraction effects of three
      processes (SFE CO2, alcohol-extraction, water-extraction) were compared by the
      contents of deoxyschizandrin, the dried extraction yield and production
      feasibility. RESULT: The method of alcohol-extraction was the best of the three
      methods, and the extraction conditions were optimized by orthogonal design as
      follows: sixfold 90% alcohol for two times and each for one hour. CONCLUSION: The
      extraction method is steady and feasible, which can be used for reference for the
      extraction process of Fructus Schisandrae Chinensis and Fructus Ligustri Lucidi.

PMID- 15506283
TI  - [Study on releasing rate of chrysophanol from Ruyi Jinhuang plaster].
AB  - OBJECTIVE: To study the releasing rate of chrysophanol from Ruyi Jinhuang
      plaster. METHOD: Based on the detecting methods of releasing rate and residual
      dosage applied in (Pharmacopoeia of P. R. C) (2000 edition), the contents of
      chrysophanol were detected by HPLC. RESULT: Chrysophanol in Ruyi Jinhuang plaster
      could well be released from plaster and to form medicinal concentration gradient.
      CONCLUSION: Chrysophanol in Ruyi-Jinhuang plaster can possibly be absorbed by
      skin.

PMID- 15506284
TI  - [Studies on chemical constituents in root of Paeonia sinjiangensis].
AB  - OBJECTIVE: To study the chemical constituents of the root of Paeonia
      sinjiangensis. METHOD: The constituents were isolated by silica column
      chromatography, and their structures were identified on the basis of spectral
      analysis and their physical-chemical constants. RESULT: Five compounds,
      paeoniflorin( I ), albiflorin (II), lactiflorin(III), daucosterol(IV), sucrose
      (V), were obtained. CONCLUSION: All of the compounds were obtained from this
      plant for the first time.

PMID- 15506285
TI  - [Studies on the chemical constituents in root bark of Polygala tenuifolia (II)].
AB  - OBJECTIVE: To study the chemical constituents of Polygala tenuifolia. METHOD:
      Isolations were performed on various chromatography columns and structure
      elucidations were aided by spectral data and chemical property analyses. RESULT:
      Four compounds were isolated from the roots of P. tenuifolia. Their structures
      were identified as sibiricose A5 (1), sibiricose A6 (2), tenuifoliside A (3) and
      3',6-disinapoyl sucrose (4). CONCLUSION: Compounds 1 and 2 were isolated from
      this plant for the first time.

PMID- 15506286
TI  - [Preliminary attempt at the speciation of 25-elements in the Chinese medicinal
      herbs].
AB  - OBJECTIVE: To make an attempt at the multi-element speciation in the Chinese
      medicinal herbs by determining the concentrations of 25 elements in different
      extraction solutions. METHOD: Firstly, five Chinese medicinal herbs (Buddleja
      officinalis, Dictamnus dasycarpus, Myristica fragrans, Albizia judibrissin and
      Inula japonica) from the same region of China were treated to obtain water
      soluble phase, lipid-soluble phase and non-soluble phase by water extraction,
      organic solvent extraction and acid digestion, respectively. Secondly, Phytolacca
      acinosa, a Chinese medicinal herb collected from 9 regions of China, was
      extracted by 0% EtOH, 50% EtOH, 75% EtOH, 95% EtOH, respectively, referring the
      Chinese Pharmacopoeia. Finally, the concentrations of 25 elements, such as Be,
      Cr, Cu, Zn, Ge, Sr, Y, Mo, Cd, Tl, Pb and REEs, in the above three phases were
      determined by ICP-MS. RESULT: Under the optimal conditions, all the 25 elements
      could be determined with detection limits ranged from 0.003 to 0.71 ng x g(-1).
      The average recoveries of the elements in P. acinosa were 88% approximately 119%,
      with the relative standard deviations 1.7% approximately 13.3%. It was observed
      that the determined 25 elements distributed in all the water-soluble, lipid
      soluble and non-soluble phases, indicating that the inorganic species,
      organicspecies, as well as the protein bound species were coexisted in the herbs.
      Big differences of the element extraction rates could be found by using different
      ethanol solutions. CONCLUSION: With the aid of the obtained results, we may
      increase the extraction of necessary elements while decrease that of the toxic
      elements from the herbs by choosing a suitable solvent during the drug
      production.

PMID- 15506287
TI  - [Quality evaluation of prepared slices of Paeonia lactiflon--determination of
      paeoniflorin by HPLC].
AB  - OBJECTIVE: To establish the quality criteria of the prepared slices of Paeonia
      lactiflon. METHOD: RP-HPLC was used for the determination of paeoniflorin in 10
      lots of samples by ultrasound-assisted extraction. RESULT: The samples were
      extracted with 50% methanol. Seperation of the solution was performed on an ODS
      column with a mobile phase of acetonitrile-water (18:82), detected at 230 nm.
      CONCLUSION: The method is simple, repeatable, accurate and applicable.

PMID- 15506288
TI  - [Determination of adenosine and cordycepin in Cordyceps sinensis and C.
      militarris with HPLC-ESI-MS].
AB  - OBJECTIVE: HPLC-ESI-MS to establish a method for simultaneous determination of
      adenosine and cordycepin in Cordyceps sinensis and C. militarris. METHOD: HPLC
      ESI-MS method. An electrospray ionization (ESI) interface and selective ion
      monitoring (SIM) mode were used. The analytical column was a 2.0 mm x 150 mm
      Shimadzu VP - ODS column and the mobile phase was water (94%), methanol (5%) and
      formic acid (1%). 2-Chloroadenosine was used as internal standard for this assay.
      RESULT: The regression equations and coefficient were Y = 0.134 6X + 0.001 29 (r
      = 0.998 4) for adenosine, Y = 0.216 4X + 0.021 5 (r = 0.999 1) for cordycepin.
      The liner range was 0.5 approximately 124.5 microg x mL(-1) and 0.5 approximately
      136.5 microg x mL(-1) for adenosine and cordycepin, respectively. The average
      recoveries of adenosine and cordycepin were 95.8% and 98.1%, respectively.
      CONCLUSION: This method is highly sensitive, fast and selective, which can be
      used for the determination of nucleosides in C. sinensis and its substitutes.
      This method can also be applied for the quality control of above herbs.

PMID- 15506289
TI  - [Study on GC-MS fingerprint analysis in rhizome of volatile oil of Acorus
      tatarinowii].
AB  - OBJECTIVE: To establish the method of fingerprint analysis on volatile oil in
      rhizome of Acorus tatarinowii by GC-MS, and to study the main characteristic
      components. METHOD: The main components of 10 samples were determined by GC-MS.
      RESULT: The injector temperature was 250 degrees C. The interface temperature was
      230 degrees C. The column flow was 1.3 mL x min(-1). The column pressure was 80
      kPa. The detector volt was 1.4 kV. The temperature rate was 3 degrees C x min(
      1). And the main characteristic components were composed of the methyleugenol
      (2.13%), cis-methylisoeugenol (4.48%), trans-methylisoeugenol (0.82%), gamma
      asarone (4.51%), beta-asarone (66.15%), alpha-asarone (6.35%). And the RSD of
      precision and reproducibility and stability was almost in the range of 5%.
      CONCLUSION: The method is reliable, accurate and can be used for fingerprint
      analysis of volatile oil of Acorus tatarinowii.

PMID- 15506290
TI  - [Quantification of isopimpinellin in root of Toddalia asiatica by HPLC].
AB  - OBJECTIVE: To determine the content of isopimpinellin in root of Toddalia
      asiatica. METHODS: A HPLC method was set up. Using Hypersil C18 column and
      methanol-water (70:30) as mobile phase, with the detection wavelength at 306 nm.
      RESULT: The linear range of isopimpinellin was 0.004 20 approximately 0.420
      microg. The average recovery was 99.7% and the RSD 2.8%. CONCLUSION: The method
      is simple and accurate, with good reproducibility, and can be used as a
      quantitative analysis method for isopimpinellin.

PMID- 15506291
TI  - [Curative machanism of Shenle capsule on 5/6 nephrectomy rats].
AB  - OBJECTIVE: To explore curative machanism of Shenle capsule on the 5/6 nephrectomy
      rats. METHOD: Fibrin plate method was applied to examine activity of urinary
      plasminogen activator(PA). Semi-quantitative analysis was used to observe stained
      intensity and area of tissue-type plasminogen activator, urokinas-type
      plasminogen activator/ plasminogen activator inhibitor(tPA, uPA/PAI-1)in remnant
      renal tissue. Northern blot was employed to analyze the expression of
      transforming growth factor (TGF-beta) mRNA. RESULT: In model control group, the
      urinary PA activity and protein expression of tPA, uPA were down-regulated, but
      protein expression of PAI-1, TGF-beta mRNA was up-regulated in remnant renal
      tissue. In each treated group, the urinary PA activity and protein expression of
      tPA/uPA were enhanced,but the protein expression of PAI-1, TGF-beta mRNA
      decreased simultaneously. CONCLUSION: Shenle capsule can delay glomerulosclersis
      and tubulointerstitial fibrotic lesions of remnant kidney by improving the
      activity of urinary PA and modulating the expression of tPA, uPA/PAI-1 and TGF
      beta mRNA.

PMID- 15506292
TI  - [An experimental study on anti-aging action of Cordyceps extract].
AB  - OBJECTIVE: To investigate anti-aging effect and mechanism of Cordyceps
      extract(CSE) on aged mice induced by D-galactose. METHOD: The aged mice were
      induced by D-galactose. Meanwhile, they were treated with three doses of CSE.
      Then the ability of learning and memory, the activity of antioxidase in the
      different tissue, the contents of MDA of brain and liver were measured after 6
      weeks. RESULT: CSE could significantly increase the ability of learning and
      memory, improve the activity of SOD of red blood cells, brain and liver, the
      activity of Na(+) -K(+) -ATPE of brain, the activity of CAT and GSH-Px of blood,
      and remarkably decrease the activity of MAO of brain and the contents of MDA of
      brain and liver. CONCLUSION: CSE has good anti-aging effects on the aged mice,
      which is probably due to effects of improving antioxidation and removing free
      radicals.

PMID- 15506293
TI  - [Effects of puerarin on number and activity of endothelial progenitor cells from
      peripheral blood].
AB  - OBJECTIVE: To investigate whether puerarin can augment endothelial progenitor
      cells (EPCs) numbers, promote EPC proliferation, migration and adhesion. METHOD:
      Total mononuclear cells (MNCs) were isolated from peripheral blood by Ficoll
      density gradient centrifugation, and then the cells were plated on fibronectin
      coated culture dishes. After 7 days culture, attached cells were stimulated with
      puerarin (to make a series of final concentrations: 0. 1, 0.5, 1, 3 mmol x L(-1))
      or vehicle control for the respective time points (6, 12, 24, 48 h). EPCs were
      characterized as adherent cells double positive for DiLDL-uptake and lectin
      binding by direct fluorescent staining under a laser scanning confocal
      microscope. EPCs proliferation, migration and in vitro vasculogenesis activity
      were assayed with MT assay, modified Boyden chamber assay and in vitro
      vasculogenesis kit, respectively. EPCs adhesion assay was performed by replating
      those on fibronectin-coated dishes, then adherent cells were counted. RESULT:
      Incubation of isolated human MNCs with puerarin dose increased the number of
      EPCs, maximum at 3 mmol x L(-1), 24 hours (approximately 1-fold increase, P <
      0.01). In addition, puerarin also promoted EPC proliferative, migratory, adhesive
      and in vitro vasculogenesis capacity. CONCLUSION: Puerarin can augment the number
      of EPCs with enhanced functional activity.

PMID- 15506295
TI  - [Study rat nephrotoxicity of Longdan Xiegan Tang].
AB  - OBJECTIVE: To investigate the nephrotoxocity of Longdan Xiegan Tang in rats, and
      to test its safety. METHOD: Sprague-Dauley rats were given Longdan Xiegan Tang
      4.5 mL x (100 mg)(-1) Bid for thirty days, and the control group was given NS.
      MTP, BUN, Cr, MDA, MTP/Ucr and SOD were measured on 1st, 2nd, 3rd, 4th week. The
      kidney tissues were viewed with light microscopy and electron microscope. RESULT:
      MTP and MTP/Ucr were obviously higher than controls ( P < 0.01), and the other
      index had no difference (P > 0.05). No remarkable structural change could been
      seen with light microscopy, but with electron microscope we could find that the
      basal membranes were thickened and some of foot process were infused. CONCLUSION:
      Longdan Xiegan Tang will result in injury of kidney function.

PMID- 15506294
TI  - [Mechanisms of muscovite on gastric mucosal protective effect].
AB  - OBJECTIVE: To explore the mechanisms of muscovite gastric mucosal protective
      effect. METHOD: Rat model of chronic gastritis were used. After gastric mucosal
      injury was induced, the rats were divided into 6 groups and were treated with
      different drugs. 2 weeks later, the tissue and blood samples were obtained and
      measured. RESULT: The general conditions, the observations under macroscopy,
      microscope and electron microscope of the middle and high dose of muscovite
      groups resembled those of the normal group. Their PH levels were higher than
      those of the model group, and the rates of intestinal metaplasia were lower, but
      the PGE2 level of the middle dose of muscovite group was the highest. CONCLUSION:
      Muscovite can be adsorbed on the surface of the gastric mucosa. It has gastric
      mucosal protective effect by improving excretion of mucus and synthesis of PGE2
      in gastric mucosa, restraining gastric acid, reversing of intestinal metaplasia
      and decreasing inflammation cells.

PMID- 15506296
TI  - [Inhibitory effect of kaempferol against binding of platelet activating factor to
      its receptor].
AB  - OBJECTIVE: To observe the platelet activating factor (PAF) antagonistic effect of
      kaempferol. METHOD: The specific binding of [3H] PAF to rabbit platelet receptor
      was investigatedwith radio ligand binding assay (RLBA). Platelet adhesion induced
      by PAF was measured with spectrophotometry. The elevation of inner free calcium
      concentration in rabbit polymorphonuclear leukocytes (PMNs) induced by PAF was
      determined with Fura-2 fluorescent technique. RESULT: The 1, 2 or 4 nmol x L(-1)
      [3H]PAF specific binding to rabbit platelet receptor was inhibited by Kae dosage
      dependently and the IC50 were 30.8, 74.6 and 92.0 micro mol x L(-1),
      respectively. The PAF induced reactions of rabbit platelet adhesion and PMNs
      inner free calcium concentration elevation were inhibited by Kae in a dose
      dependent manner. The IC50 of Kae to inhibit platelet adhesion was 65 micromol x
      L(-1). CONCLUSION: Kae is effective in inhibiting the action of PAF and it is a
      new PAF receptor antagonist.

PMID- 15506297
TI  - [Studies on the effects of Siwu Mixture on reversing multidrug resistance of
      human erythrocyte leukemic cell line K562/ADM].
AB  - OBJECTIVE: To study the effects of Siwu Mixture on reversing the multidrug
      resistance (MDR) of human erythrocyte leukemic cell line K562/ADM. METHOD: With
      verapamil set as a positive control, MTT assay was applied to evaluate the
      resistant factor of cell line K562/ADM to anticancer drugs and the reversal index
      of Siwu Mixture on MDR of the cells. The concentration of adriamycin(ADM) in the
      cells was measured by reversal-phase high performance liquid chromatography. The
      immunofluorescence method was used to determine the expression of P
      glucoprotein(Pgp) on cell membrane. RESULT: When ADM was combined with Siwu
      Mixture, its concentration in the cells and the reversal index of MDR were
      significantly higher than those of blank control (P < 0.01). However, the
      expression of Pgp on cell membrane showed little difference ( P > 0.05).
      CONCLUSION: In case of noncytotoxic dose, Siwu Mixture showed significant effect
      on reversing MDR of cell line K562/ADM. The effect might be related to decreasing
      efflux of anticancer drugs in the cells and increasing their concentration in the
      cells. Nevertheless, it had no influence on the expression of Pgp on cell
      membrane.

PMID- 15506298
TI  - [Pharmacodynamical research of Jingu Tongxiao granule].
AB  - OBJECTIVE: To study functions of Jingu Tongxiao granule (JGTXG, treatmenting ache
      of bones and muscles) in antiphlogistic and antalgic aspect, invigorating the
      circulation of blood and absorbing clots and antitraumatic soft tissue. METHOD:
      Animal models of inflammation, ache, gore and traumatic soft tissue were adopted,
      and pharmacodynamic actions of Jingu Tongxiao granule were observed. RESULT:
      JGTXG could conspicuously restrain inflammatory reactions of mouse ear tumid
      model treated by croton oil tumid and rat foot metatarsus tumid model treated by
      carrageenan, and restrain pain responses of mouse caused with whipping back end
      method by heat stimulating and of mouse caused with wriggling body method by
      acetic acid being injected in its abdominal cavity. It could significantly
      improve petechia degree in traumatic rat blood stasis model, and prominently
      improve raumatized limb's tumefaction degree and alleviate blood stasis, swelling
      and phlogistic cell soakage in traumatic rat soft tissue model. At the same time,
      it could prominently restrain platelet aggregation and improve whole blood
      viscosity. CONCLUSION: Jingu Tongxiao granule has antiphlogistic and antalgic
      functions, invigorating the circulation of blood and absorbing clots and
      antitraumatic soft tissue, and it could keep curative effect of original dosage
      form.

PMID- 15506299
TI  - [Dynamical examination of auditory event-related potentials P300 and sympathetic
      skin response in people with insomia of Sweet Dream Capsule therapy].
AB  - OBJECTIVE: To observe the change of auditory event-related potentials (P300) and
      sympathetic skin response (SSR) in people with insomia of Sweet Dream Capsule
      therapy. METHODS: 30 patients meeting criteria for primary insomnia and 30
      healthy volunteers with age matching controls were selected for the study. P300
      and SSR were measured before treatment of Sweet Dream Capsule and at week 4 , 8
      of the therapeutic course. That the change of P300 and SSR before and after
      treatment and their relations with PSQI were studied. RESULT: Compared with those
      of normal controls, both P300 latency and SSR latency were prolonged while
      amplitude was decreased in patients with insomnia (P < 0.01). P300 amplitude was
      increased significantly at central (Cz) electrode sites only at week 8 when
      compared with amplitude before treatment (P < 0.05). With improvement of symptom
      and PSQI scores, latency and amplitude of SSR were improved at week 4 and week 8
      (P < 0.05 and P < 0.01) . CONCLUSION: P300 has a some improvement in people with
      insomia of Sweet Dream Capsule therapy while SSR im proves significantly, and
      PSQI scores are ameliorated too.

PMID- 15506300
TI  - [Clinical study on compatibility and dismantlement of Xuefu Zhuyu decoction].
AB  - OBJECTIVE: To investigate the regularity of traditional Chinese compound
      prescription by observing the clinical effect of the compatibility and
      dismantlement of Xuefu Zhuyu decoction on blood stasis and stagnation of qi
      syndrome of angina. METHOD: 123 outpatients were randomly divided into Xuefu
      Zhuyu group(XF), Jingzhi Xuefu Zhuyu group(JZ), Yaodui group(YD) and placebo
      group and treated. RESULT: The array of angina effect and blood stasis and qi
      stagnation of syndrome effect was XF group, JZ group, YD group, placebo group( P
      < 0.01). The levels of blood viscosity, platelet adhesiveness, RED transfigure
      were significantly different before and after treatment in XF group (P < 0.05).
      The levels of blood viscosity, platelet adhesiveness were significant different
      before and after treatment in JZ group ( P < 0.05). The levels of blood plasma
      viscosity, platelet adhesiveness were significantly different before and after
      treatment in YD group ( P < 0.05). The levels of platelet adhesiveness, RED
      transfigure were significantly different before and after treatment in placebo
      group (P < 0.05). There are no difference among levels of blood lipoprotein and
      ET of four groups ( P > 0.05). Significant difference was found among four groups
      in increase of NO and t-PA and decrease of IL-6 (P < 0.05). CONCLUSION: The
      clinical effect and indexes amelioration are correlated to the combination of
      prescription and the corresponding degree of prescription to syndrome. There are
      same material foundation in the series of Xuefu Zhuyu dismantle decoction, but
      the function degree and targets are different with the change of herbs. The
      method of conjugating disease and syndromes, and prescription to syndromes are a
      practical pattern to expound the relationship between disease and syndrome.

PMID- 15506301
TI  - Program proposal for medical studies at the University of Maribor Medical
      Faculty.

PMID- 15506302
TI  - Prevalence of HIV, hepatitis B, C and G virus infections among injecting drug
      users on methadone maintenance treatment in Maribor.
AB  - The prevalence of human immunodeficiency virus (HIV) infection and hepatitis B,
      C, and G virus infections was determined in a selected group of 40 intravenous
      drug addicts on methadone maintenance treatment. No drug addict was infected with
      HIV. Seven drug addicts (17.5%) had serologic markers of hepatitis B infection
      but only one among them (2.5%) exhibited signs of active infection. 16 drug
      addicts (40%) had serologic markers of hepatitis C infection and 13 (32.5%) of
      them had an active infection with positive viral tests. 22 addicts (55%) had
      signs of hepatitis G infection, 9 (22.5%) of them had signs of active infection
      and 13 (32.5%) had signs of past infection. Addicts infected with the hepatitis B
      and C viruses were older and had also been taking drugs longer than those who
      were not infected with these two viruses. The proportion of those susceptible to
      infection with hepatitis B (70%) is high, reflecting a low prevalence of this
      disease and at the same time revealing the failure of preventive measures and the
      unacceptably low vaccination rate.

PMID- 15506303
TI  - The prevalence of celiac disease among family members of celiac disease patients.
AB  - INTRODUCTION: Celiac disease (CD) is more common in certain risk groups. Family
      members of known celiac patients represent the most important group. Serological
      screening enables us to detect patients before they develop serious
      complications. HLA typing has also proven to be a valuable diagnostic tool,
      especially in excluding the disease. METHODS: To assess the prevalence of CD
      among family members, we screened 106 first-degree relatives (73 parents, 33
      siblings; mean age 27.9 years) of 45 celiac patients in NE Slovenia. We analysed
      antigliadin (AGA) and antiendomysium (EMA) antibodies. Levels of IgG and IgAAGA
      were determined using the ELISA method, and EMA using indirect
      immunofluorescence. Serologically positive patients were recalled for intestinal
      biopsy and were HLA typed. Intestinal biopsy was performed by peroral aspiration
      capsule or during upper GI endoscopy. Biopsy specimens were examined
      histologically. RESULTS: Six family members (5.67%) were both AGA IgG and EMA
      positive, and one (0.94%) was only EMA positive. All were either HLA DQ2 or DQ8
      positive. Nine family members (8.49%) were only AGA IgG positive, two of them
      lacked the HLA DQ susceptibility alleles. Intestinal biopsy was performed in six
      family members, and the diagnosis of CD confirmed in five. All were both AGA IgG
      and EMA positive. They were either symptom-free or had only mild gastrointestinal
      symptoms, and carried the known HLA DQ risk alleles. The minimum prevalence of CD
      among family members in NE Slovenia can therefore be estimated at 4.72%.
      DISCUSSION: The prevalence of CD among first-degree relatives is much higher than
      the prevalence of the disease in the general population. Most of these patients
      have an atypical form of the disease and would therefore be overlooked without an
      active search. Serological testing is recommended for all first-degree relatives
      of CD patients; they should also undergo HLA typing to detect those whose HLA
      phenotype is consistent with CD. This approach can also help in excluding
      individuals who do not need further diagnostic procedures for CD.

PMID- 15506304
TI  - [Endovascular treatment of intracranial artery aneurysms in the posterior
      cerebral circulation].
AB  - The purpose of the study was to determine the safety and effectiveness of
      electrolytically detachable platinum coils in the endovascular treatment of
      ruptured and unruptured aneurysms in the posterior cerebral circulation. The
      aneurysms were occluded with electrolytically detachable platinum coils. Six
      patients with posterior cerebral circulation aneurysms were treated. Four
      patients suffered a subarachnoid hemorrhage, in two patients the aneurysms were
      detected incidentally, in one due to mass effect. In all six patients, the
      diameters of the aneurysms were less than 12 mm and were therefore classified as
      small aneurysms. Complete occlusion (100%) was achieved in 4 patients, the rate
      of occlusion in the other two patients was estimated at 75% in one case and at
      90% in the other. The clinical outcome in five patients was excellent, without
      any additional neurological deficit. One patient died five weeks after the
      procedure due to respiratory complications. At the time of endovascular
      treatment, she had been graded clinically as grade 5 according to Hunt and Hesse.
      None of the patients experienced any recurrence of hemorrhage during the follow
      up period of 12 months. Endovascular occlusion of posterior cerebral artery
      aneurysms with detachable coil system is an effective alternative therapy to
      established surgical treatment and could become the treatment of choice. The
      method is minimally invasive and there is no need for skull trepanation.

PMID- 15506305
TI  - A review of civilian gunshot wounds to the head in northeast Slovenia: 1992 to
      2002.
AB  - BACKGROUND: Surgical management of gunshot wounds to the head has remained a
      controversial issue. There are considerable regional differences in the causes of
      civilian gunshot wounds (GSW) to the head and various devices are used in
      different countries. The aim of our study was to review the demographic factors,
      treatment and outcome of patients with GSW to the head over the past 10 years at
      Maribor Teaching Hospital. PATIENTS AND METHODS: Thirty-seven patients with GSW
      to the head (35 male and 2 female; mean age 43.3 +/- 15.5 years) were included in
      the study. Clinical and radiological findings are described. Statistical analysis
      was used to find the effects of all independent variables on mortality and
      prognostic factors. RESULTS: The great majority (86.5%) of our patients suffered
      self-inflicted wounds. The weapon used was a stunning device in 54% of cases and
      a handgun in 46%. Alcohol consumption was documented in 40% patients. Nearly half
      (48.9%) of our patients were either industrial workers or farmers.
      Postresuscitation Glasgow Coma Scale (GCS) scores of 3-8 were recorded in 54%.
      The pupils were fixed and dilated in 32.4% of our patients; hypotension was
      documented in 8.1% and apnea in 27%. These parameters were significantly
      correlated with poor outcome. A bihemispheric lesion was found in 37.8%, a
      transventricular lesion in 54% and a multilobar lesion in 70.3% of patients.
      Those factors were also associated with poor outcome. The majority of patients
      (56.8%) underwent operation immediately, in 13.5% the operation was delayed and
      29.7% of patients had no surgery. The overall mortality was 51.4%, a poor outcome
      was noted in 24.3% and a good one was achieved in 24.3%. CONCLUSION: The results
      of our study support previous ones stating that patients with GSW to the head can
      benefit from aggressive treatment and still make satisfactory recoveries.
      Clearly, there are ethical dilemmas involved in withholding operative treatment
      from any individual. Guidelines dictating when to surgically intervene must be
      made.

PMID- 15506306
TI  - Clinical versus electrodiagnostic effectiveness of splinting in the conservative
      treatment of carpal-tunnel syndrome.
AB  - BACKGROUND: Splinting is known as one of the most effective non-aggressive
      treatments for carpal-tunnel syndrome (CTS). Early and accurate diagnosis of CTS
      is critical for effective non-surgical management. Nerve-conduction studies
      confirm the diagnosis of CTS with a high degree of sensitivity and specificity.
      Many patients report that their symptoms decrease after splinting; consequently,
      improved electrophysiological findings are expected. OBJECTIVE: The aim of the
      study was to evaluate the clinical and neurophysiological effectiveness of
      splinting in patients with CTS. METHODS: In a prospective study of 77 hands with
      CTS symptoms, neurophysiological tests were performed before and after 12 weeks
      of using a splint. A custom-made volar thermoplastic wrist splint was fabricated
      in a neutral wrist position to maximize carpal-tunnel space and minimize the
      compressive forces on the median nerve. Each patient was provided with a custom
      made splint, and was asked to wear it during sleep and whenever possible when
      awake. The case history was taken, and a physical examination and repeated nerve
      conduction studies were performed at the start and after 12 weeks. Data were
      analysed statistically. RESULTS: We calculated the mean and the range for each
      electrophysiological test before and after 12 weeks of splint use. There was no
      significant difference between pre- and post-measurement of each parameter (p >
      0.05). Good relief of symptoms occurred soon after the patients began wearing the
      splint; however, the electrodiagnostic test remained pathological. CONCLUSION:
      Even though immobilization (wrist splint in neutral position) does not affect the
      common electrodiagnostic parameters in CTS diagnostics, it caused the
      disappearance of clinical symptoms in 75% of the patients. There is therefore a
      need for further research regarding the usefulness of repeated electrodiagnostic
      studies.

PMID- 15506307
TI  - The significance of thoracoscopic mechanical pleurodesis for the treatment of
      malignant pleural effusions.
AB  - BACKGROUND: Malignant pleural effusion (MPE) is a frequent and serious
      complication of numerous malignant tumors in the human organism. The patients are
      suffering from the primary disease, and the pleural effusion causes dyspnea, thus
      reducing the quality of their survival time. In our study we wished to establish
      the significance of thoracoscopic mechanical pleurodesis (TMP) as a new method
      for the resolution of this pathology, by comparing the results with those of
      thoracotomy with pleurectomy (TP) and thoracic drainage (TD). The main criterion
      for the effectiveness of each method was the absence of pleural effusion in a
      certain time interval. PATIENTS AND METHODS: 84 patients with recurrent MPE and
      primary tumors at various locations were divided into three groups according to
      the type of palliative intervention. The patients were classified according to
      the indication guidelines for individual procedures and their general condition.
      Group 1 consisted of 44 patients in whom TMP was performed, group 2 consisted of
      17 patients with primary tumors in the thoracic region in whom thoracotomy with
      pleurectomy (TP) was performed, and in group 3 there were 26 patients with TD. We
      compared the effectiveness of individual palliative methods by periodical X-ray
      checks, numbers of complications, length of TD and hospitalization, and changes
      in spirometric values after individual procedures. The t-test was used in
      statistic processing of the data. RESULTS: After six months, radiological
      investigation revealed recurrence of pleural effusion in three patients in group
      1 (93.2% efficacy), no recurrence in group 2 (100% efficacy), and recurrence in
      18 patients in group 3 (25.0% efficacy). There were fewer postoperative
      complications in group 1, the duration of TD and hospitalization was
      significantly shorter, and spirometric values increased. CONCLUSION: TMP is an
      effective palliative method for the treatment of recurrent pleural effusions,
      with a minimum number of complications and a short period of hospitalization.
      After TMP there is significant improvement in respiratory functions, and for the
      patient it represents a relatively simple surgical procedure. TP is indicated in
      the treatment of tumors and subsequent MPE in the thoracic region, and TD is
      indicated in patients who are not suitable candidates for one of the palliative
      pleurodesis procedures, because of either their poor general condition or a
      trapped lung.

PMID- 15506308
TI  - Incidence and outcome of rupture of the Achilles tendon.
AB  - We determined the incidence of complete rupture of the Achilles tendon in the
      Maribor region (273,609 inhabitants) between 1991 and 1996. During this period,
      116 ruptures were treated at Maribor Teaching Hospital. The average incidence was
      7 ruptures per 100,000 inhabitants, with a peak incidence of almost 9 per
      100,000. Most injuries (65%) occurred during sports activities, with soccer as
      the major cause of rupture. The average age of patients was 37 years with a male
      to-female ratio of 18:1. All patients underwent open surgical repair of the
      ruptured Achilles tendon, with a minimum follow-up of two years. 19.8% of cases
      developed complications and in 10.4% of these the complications were major. 1.9%
      of patients sustained a re-rupture. The mean AOFAS score was 96 points. The
      patients were subjectively very satisfied with their treatment in 88% of cases.
      Good functional results with a return to the usual pre-injury activities were
      achieved in 96% of patients.

PMID- 15506309
TI  - Epidemiological study of cerebral palsy in the Maribor region.
AB  - BACKGROUND: The results of changes in perinatal health care in Maribor show a
      significant improvement in the past decade. Between 1995 and 1999, the survival
      chances of neonates with birth weight < 1000g also increased. With the appearance
      of new generations of extremely low-birth-weight infants, the risk of a higher
      incidence rate of various forms of neurosensory affection in the survivors
      increased. METHODS: We determined trends in the incidence of cerebral palsy (CP)
      in live birth and one-year survivor cohorts of children in the Maribor region for
      the decade 1988-1998. We identified children with CP in the Maribor region by
      record review as part of an ongoing developmental disability surveillance program
      conducted by the Centers for children with developmental disturbances at the
      Public Health Centers of the Maribor region (Maribor, Lenart, Ptuj, Ormoz and
      Slovenska Bistrica). A total of 123 cases of congenital CP were identified for
      the birth years 1988-1998. Data were analyzed according to birth weight,
      gestational age, subtypes of CP, and whether CP existed as an isolated disability
      or was accompanied by another disability. We compared the data for 1988-1993 with
      those of 1994-1998. RESULTS: There was a modest increase in the overall incidence
      of congenital CP from 3.7 to 4.3 per 1000 one-year survivors during the second
      part of the 1988-1998 decade. This trend was primarily attributable to an
      increase in CP in children with low or extremely low birth weight. There was an
      increase in the proportion of children who had both CP and other disabilities,
      most apparent in infants with birth weight > 2500g, from 53% in 1988-1993 to 62%
      in 1994-1998. For children weighing < 1500g, the proportion of children with
      spastic diplegic CP increased during the decade (62% in 1988-1993 and 78% in 1994
      1998); for children weighing > 2500g, the proportion with spastic diplegia
      decreased (62% in 1988-1993 and 44% in 1994-1998). CONCLUSION: In a decade in
      which perinatal mortality was halved and survival among neonates with birth
      weight under 1500g increased to 90% in the second part of the decade, the average
      incidence of CP in the Maribor region increased slightly from 3.7 per 1000
      survivors in 1988-1993 to 4.3 per 1000 survivors in 1994-1998. This increase was
      seen in infant survivors with birth weight < 1500g. Although no change was seen
      in the trends in CP incidence in low-birth-weight infants, a decrease was seen in
      infant survivors with birth weight > 2500g.

PMID- 15506310
TI  - Outcome of stenosis of the internal carotid artery after contralateral
      endarterectomy.
AB  - OBJECTIVES: The aim of the study was to evaluate clinical outcome and patterns of
      disease progression relating to stenosis of the internal carotid artery (ICA)
      opposite to the operated side, using ultrasonographic risk score of ICA plaques.
      METHODS: 150 patients who underwent ICA endarterectomy for transient ischemic
      attack (TIA) between January 1997 and December 2000 were studied prospectively.
      The progress (modified Strandness criteria) and ultrasonographic morphology of
      ICA plaques on the contralateral side were followed using digitally assisted
      plaque analysis. Parameters of the plaque image were analyzed and compared with
      neurologic events. RESULTS: Progression of contralateral stenosis from < 50% to
      50-79% occurred in 11/105 patients (10.5%), all asymptomatic; from 50-79% to 80
      99% in 10/31 patients (9.5%, one TIA). One patient progressed from the > 50%
      group to the 80-99% group and remained asymptomatic. After the progression of
      stenosis there were 32 patients with 50-79% stenosis and 25 with 80-99%. Among
      those with 50-79% stenosis, two patients developed symptoms (one TIA and one
      stroke). Among those with 80-99% stenosis, three patients developed symptoms (two
      TIAs and one stroke). Of the 105 patients who began with an initial contralateral
      stenosis of <50%, there remained 93; Seven developed symptoms appropriate to the
      contralateral carotid artery (four TIAs and three strokes). Life-table comparison
      (Cox's F test) of patients with < 50% stenosis (N = 93) and those with > 50%
      stenosis (N = 57, groups with > 50% stenosis taken together) showed no important
      statistical connection (F =1.71, p = 0.378). All plaques were heterogenous and
      there was no difference in global echogenicity. However, the activity index (AI)
      in patients with more than 50% stenosis (N=57, groups 50-79% and 80-99% together)
      was higher than 60 in 19 patients and lower than 60 in 38 patients. There were
      four neurologic events (three TIAs, one stroke) in the first group (AI > 60) and
      one neurologic event in the second (one stroke). Life-table comparison (Cox's F
      test) of the two groups based on the AI showed a significant difference (F=8.84,
      p=0.001). 18 patients were operated on the contralateral side on the basis of an
      elevated ultrasonographic AI. There was no morbidity or mortality in the operated
      group. CONCLUSIONS: Digitally assisted analysis of ultrasonographic ICA plaque
      morphology is unable to identify high-risk plaques in patients with less than 50%
      stenosis. In asymptomatic patients with more than 50% stenosis, an
      ultrasonographic plaque AI higher than 60 may contribute to a more objective
      selection of patients for operation.

PMID- 15506311
TI  - The measurement of stenosis of the internal carotid artery: comparison of doppler
      ultrasound, digital subtraction angiography and the 3D CT volume rendering
      technique.
AB  - OBJECTIVES: To determine the variability of measurement of stenosis of the
      internal carotid artery (ICA) using Doppler ultrasound, digital subtraction
      angiography (DSA) and the three-dimensional volume rendering technique (3D CT) in
      the high-grade stenosis band (70-100%). DESIGN: A prospective study of
      preoperative findings in 64 patients. MATERIAL AND METHODS: Doppler ICA stenosis
      was assessed according to combined Doppler acoustic standard criteria (CDASC) and
      peak systolic velocity (PSV). DSA and 3D CT stenosis were measured using the
      NASCET method. The results were compared using kappa statistics and Pearson's
      correlation coefficient. RESULTS: Agreement on the degree of ICA stenosis was
      statistically very good for DSA and 3D CT (kappa = 0.81, CI 0.69-0.93): Pearson's
      correlation coefficient was 0.88 (CI 0.76-0.90). The comparison of Doppler
      ultrasound with DSA showed good agreement (kappa 0.70, CI 0.58-0.82): Pearson's
      correlation coefficient was 0.61 (CI 0.43-0.74). The disagreement rate on
      occlusion was 3% between DSA and 3D CT and was rather high (10.9%) between
      Doppler ultrasound and DSA. CONCLUSIONS: The clinical decision to operate on an
      ICA stenosis will be strongly influenced by the diagnostic method used. DSA and
      3D CT correlate well, whereas Doppler ultrasound tends to differ at the high end
      of the high-grade stenosis band (90% occlusion), underestimating (compared with
      DSA) the degree of stenosis.

PMID- 15506312
TI  - What have we learned from surgical treatment of gastric adenocarcinoma? A
      comparison of two periods.
AB  - In January 1992, a standardized and more radical surgical approach in gastric
      cancer treatment and a standardized pathohistological workup of specimens was
      introduced at our institution. The aim of our retrospectively designed study was
      to compare the results of two consecutive groups of altogether 348 patients who
      underwent a total or subtotal gastrectomy for gastric cancer (period A: 162
      patients operated between 1992 and 1996; period B: 186 patients operated between
      1997 and 2000). The two groups of patients were comparable in age, sex, their
      general condition, and the proportion of potentially curable (R0) resections.
      There was a significant difference between the groups with regard to tumor site
      (fewer distal and more proximal stomach tumors in period B), type of operation
      (more total gastrectomies in period B), extent of lymphadenectomy (more D2 and D3
      in period B), average number of affected lymph nodes (higher in period B),
      average number of examined nodes (higher in period B), and in UICC stage (less
      stage II in period B). UICC classification was impossible in 19 patients overall,
      but there were fewer non-classified patients in period B. The incidence of
      surgical complications (15.6% vs. 18.7%) and average hospital stay (14.72 days
      vs. 14.70 days) was not significantly different in the two groups. The drop in
      overall mortality rate (potentially curable and non-curable resections) in period
      B almost reached statistical significance (period A: 8%, period B: 6.5%; p =
      0.57). The 5-year survival for all R0 resected patients (279) in 9 years was 31%.
      The median survival was significantly longer in period B (941 days) than in
      period A (570 days) for R0 and non-curable (R2) resections together (p=0.0132) as
      well as for R0 resections alone (period A: 844 days, period B: 1176 days; p =
      0.0127). Comparison of the two consecutive groups of patients shows that after a
      defined period of systematic surgical work our results improved, reflected in the
      higher number of extracted lymph nodes, the higher number of total gastrectomies,
      and the longer median survival in the second period.

PMID- 15506313
TI  - Abscess formation within cerebellar metastatic carcinoma--report of two cases and
      review of the literature.
AB  - BACKGROUND: The occurrence of an abscess in conjunction with a tumor in the brain
      is very rare. Only presumptions exist about their origin and manner of
      dissemination. Preoperative discrimination between a brain tumor with cystic
      degeneration and a brain abscess within a tumor may be difficult or even
      impossible. The purpose of this report is to demonstrate the difficulty of such
      discrimination using conventional CT diagnostics alone. METHODS: Two patients
      with abscess formation in association with metastatic carcinoma in the cerebellum
      are presented and compared with similar cases in the literature. The etiology and
      the route of dissemination are discussed. RESULTS: In our first patient with
      previously diagnosed lung carcinoma and a CT showing suspected cerebellar
      metastasis only, an abscess caused by Propionibacterium acnes was found in the
      cerebellum and treated surgically. No tumor was recognised during the operation.
      Post-mortem examination six weeks later revealed the coexistence of remnants of a
      chronic abscess as well as metastatic lung carcinoma at the operation site. The
      second patient presented with an enhanced, ring-like cystic cerebellar lesion.
      During surgery, a purulent exudate with a coagulase-negative type of
      Staphylococcus species was found within the metastatic carcinoma of unknown
      origin. Both were radically excised and the patient recovered well. Neither
      patient had a history of previous infection and the pathway for abscess formation
      in both patients remained unclear. About 30 cases of abscesses associated with
      intracranial neoplasms were found in the literature. Including our own report,
      only three cases of abscesses within metastatic carcinoma have been published.
      CONCLUSIONS: Modern diagnostic tools reported to differentiate more reliably
      between an abscess and a tumor are diffusion-weighted MR and proton MR
      spectroscopy techniques. Brain imaging using CT alone may not reliably
      demonstrate both coexisting lesions or differentiate between them. It is
      important to know that a metastatic brain lesion can occur in association with a
      brain abscess and that tissue sampling for pathological as well as
      microbiological testing is of crucial importance for optimal therapy for both
      lesions.

PMID- 15506314
TI  - Endovascular treatment of arteriovenous malformation in a child.
AB  - Arteriovenous malformations are direct communications between the arterial and
      venous circulations without the usual passage through the capillary net. They are
      the most frequent type of malformations of the intracranial circulation and the
      second most frequent cause of intracranial hematomas or hemorrhage. We report on
      a 7-year-old girl with intracerebral hematoma following acute rupture of an
      arteriovenous malformation. The girl experienced a spontaneous headache and later
      became unconscious. At the time of admission to the hospital, her neurological
      status scored 5 on the Glasgow Coma Scale. Computerized tomography of the brain
      revealed a round hyperdense lesion in the left frontoparietal region. Digital
      subtractional angiography of the left internal carotid artery confirmed the
      suspicion of an arteriovenous malformation with one main feeding artery: a distal
      branch of the left anterior cerebral artery. The nidus was round and about 2 cm
      in diameter. The venous drainage was of the superficial type, flowing into the
      left superior sagittal sinus. After consultation with a neurosurgeon, we decided
      to treat the arteriovenous malformation by means of an endovascular technique. A
      flow-guided catheter was placed close to the nidus. Control angiography before
      embolization revealed the proper position for the injection of embolic material.
      We used the conventional mixture of acrylic polymerization glue, Lipiodol oil
      contrast medium and particles of tantalum powder. Control angiography at the end
      of the procedure revealed complete occlusion of the malformation. There were no
      signs of potential new feeding arteries that could appear as a result of changed
      hemodynamic conditions after embolization. Endovascular treatment of
      arteriovenous malformations could become the treatment of choice for these
      lesions, especially in combination with radiosurgery. The established
      microsurgical treatment is very effective but carries a higher risk of
      hemorrhagic complications.

PMID- 15506315
TI  - Solitary fibrous tumor of the parapharyngeal space.
AB  - Solitary fibrous tumors are rare tumors originating from the mesenchymal tissue.
      In most cases they arise from the subpleural tissue but have also been described
      in other locations in the body. Most such tumors in the head and neck region
      occur in the orbit. Although malignant tumors can occur, benign tumors are far
      more common. The therapy is surgical excision. For a conclusive diagnosis, a
      typical morphology and immunohistochemistry are required. The tumor is strongly
      positive for CD34 and vimentin. This report describes the clinical appearance and
      treatment of a solitary fibrous tumor of the parapharyngeal space in a female
      patient. The symptoms were similar to those in a peritonsillar abscess, one of
      the more common ear-nose-throat dysfunctions. Fewer than 10 cases of a solitary
      fibrous tumor of the parapharyngeal space have been described in the literature.

PMID- 15506317
TI  - The Charles Bonnet syndrome: a case report.
AB  - The Charles Bonnet syndrome is a condition in which individuals experience
      complex visual hallucinations without evident psychopathology or disturbance of
      normal consciousness. Although it can affect people of any age, it is more
      frequent among the elderly. It occurs mostly in people with damaged sight, as a
      result of peripheral eye pathology or pathology within the brain. A common
      definition of the syndrome is, however, not yet available nor has its
      pathophysiology been elucidated. This report concerns a 72-year-old widow who was
      practically blind after a cataract operation on both eyes ten years ago. Visual
      hallucinations appeared in the absence of other psychopathological symptoms.
      During hospitalization of the patient, an extensive meningeoma sellae turcicae
      was discovered, which destroyed both nervi optici. This case shows that multiple
      causes of the Charles Bonnet syndrome should be taken into consideration and that
      an exact diagnostic evaluation is essential.

PMID- 15506316
TI  - First branchial cleft anomaly, a case for misdiagnosis.
AB  - First branchial cleft anomaly is a rare condition that is often misdiagnosed and
      falsely mistreated before complete and definitive surgical treatment. Its origin
      is uncertain and the presence of ectodermal and sometimes also mesodermal
      elements has led some authors to the conclusion that it represents buried nests
      of cells forming the first branchial cleft and the underlying mesoderm. First
      branchial cleft anomaly can be presented as a cystic lesion, fistula or sinus
      extending towards the membranous external ear canal. The sinus tract runs through
      the parotid gland in close association with the facial nerve. There is no imaging
      method capable of identifying a first branchial cleft anomaly with certainty. The
      danger of facial nerve injury during surgery and the failure to identify the
      sinus tract running to the external ear canal are the main reasons for incomplete
      excision. The facial nerve must be identified and preserved and the lesion
      completely excised. Facial nerve injury is more common in attempts to remove
      recurrent branchial cleft lesions.

PMID- 15506318
TI  - An unusual generalized form of hyperkeratosis lenticularis perstans (Flegel's
      disease).
AB  - An 82-year-old female presented with an 11-year history of multiple,
      symmetrically disseminated hyperkeratotic red-brown papules 3-5 mm in diameter on
      the dorsal aspects of the upper and lower extremities. The eruption first
      appeared on the dorsa of the feet and on the lower parts of the legs. During the
      last few years, the lesions extended gradually to the upper part of the legs and
      thighs, also disseminating over the trunk. There was no family case history of
      Flegel's disease. Histopathological examination revealed a hyperkeratosis with a
      focal parakeratosis overlying the thinned epidermis. In the papillary dermis
      there was a dense band-like infiltrate composed of lymphocytes and some
      histiocytes. Electron microscopy showed a normal number of membrane-coated
      granules (Odland bodies). The clinical and histopathological findings in the
      patient corresponded with the diagnosis of hyperkeratosis lenticularis perstans.
      The patient was treated with PUVA (psoralen plus ultraviolet A)-bath therapy,
      retinoid plus PUVA and calcipotriol. However, all of these treatments were
      unsuccessful.

PMID- 15506319
TI  - Grover's disease: successful treatment with acitretin and calcipotriol.
AB  - A 74-year-old man presented with a five-month history of highly pruritic
      keratotic papules on the trunk and extremities. Laboratory data revealed mild
      eosinophilia, elevated IgE (483KE/I) and no other signs of atopy. Tests to
      exclude parasitic infestation were negative. Two biopsies showed non-specific
      changes. The third biopsy revealed small acantholytic clefts in the upper part of
      the epidermis and confirmed the diagnosis of Grover's disease. Topical treatment
      with calcipotriol ointment and systemic treatment with acitretin in low doses
      successfully reduced the pruritus within one week, and brought about a complete
      remission within three weeks without any recurrence.

PMID- 15506320
TI  - An anatomical variation of the origin of the human right inferior thyroid and
      bronchial arteries.
AB  - During routine anatomical dissection we found an unusual case of origin of the
      right bronchial artery from a common stem with the inferior thyroid artery, which
      arose from the internal thoracic artery. Anatomical variations of the origin of
      bronchial arteries are very frequent and numerous, and their recognition may be
      helpful in certain surgical and diagnostic procedures.

PMID- 15506321
TI  - Brain abscess after milk tooth self-extraction.
AB  - Brain abscesses are rare, especially in children, but they can be life
      threatening infections. To date, dental pathology has been linked to only a small
      number of brain abscesses. To our best knowledge this is the first reported case
      of a brain abscess following self-extraction of a milk tooth. We are reporting on
      a 12-year-old previously healthy boy who developed a brain abscess in the
      vicinity of the left precentral gyrus. Clinical examination prior to surgery
      showed a severe right hemiparesis, more pronounced in his leg. We performed an
      ultrasonographically guided puncture and aspiration of the abscess through a
      small craniotomy. Immediately after the procedure he became hemiplegic.
      Bacteriological examination of the aspirated pus revealed Streptococcus
      intermedius, Streptococcus beta-haemolyticus group F, Fusobacterium species and
      gram-negative rods. The same species of microorganisms were identified in a smear
      from the vicinity of the extracted tooth. The patient was carefully screened for
      possible other sources of infection, but none was found. Following appropriate
      antimicrobial treatment he recovered completely and returned home without any
      neurological deficit.

PMID- 15506322
TI  - The unilateral stapes gusher.
AB  - A stapes gusher is an alarming situation occurring during stapes surgery for
      mixed hearing loss. It is characterized by the sudden profuse flow of
      cerebrospinal fluid in the middle ear and external ear canal after opening the
      vestibule of the inner ear. An adult patient with unilateral stapes gusher is
      described; he was operated on both ears with a good hearing result on both sides.
      The stapes on the side with the cerebrospinal fluid leak was malformed,
      especially in the posterior crus--a finding which may suggest the possibility of
      a stapes gusher. The small-hole stapedotomy is a safe technique when dealing with
      a profuse cerebrospinal fluid leak, and it enables the closure of the leak with
      additional tamponade of the oval niche and the achievement of a good hearing
      result.

PMID- 15506323
TI  - Recurrent giant invasive thoracolumbar schwannoma.
AB  - Giant invasive spinal schwannoma is a new term proposed by Sridhar in 2001 for a
      particularly aggressive type of benign spinal schwannoma. Only a few cases have
      been published, the majority of these located in the lumbosacral spine, two in
      the thoracic and only one in the cervical spine. A rare case of such a tumor is
      presented. The tumor predominantly occupied level L1 and partially levels T12 and
      L2, and recurred 13 years after the first seemingly radical excision of a benign
      melanotic schwannoma. The highly vascularized tumor was radically excised using
      the dorsal approach, and a Sokon transpeduncular fixation was performed. Carter's
      lateral thoraco-abdominal access allowed the retroperitoneal and intravertebral
      expansions of the tumor to be removed and L1 corpectomy to be accomplished.
      Ventral vertebral stabilization was achieved with a titanium cage. After the
      operation, the pain in the patient's left leg subsided. Three years after the
      management, he is still pain-free, able to walk freely and to resume his usual
      daily activities.

PMID- 15506324
TI  - Abdominal actinomycosis presenting as a small-bowel obstruction.
AB  - A 48-year-old female, presented as a case of acute abdomen with a small-bowel
      obstruction and a palpable hypogastric mass, was urgently operated. Laparotomy
      revealed a tumor mass of unknown origin that included a loop of the small bowel
      by compressing it. Resection of the tumor including a portion of the large and
      small bowel was performed, and pathohistological examination revealed
      actinomycosis. The cause of abdominal actinomycosis in this patient could be the
      implantation of an intrauterine device nine years prior to the operation.

PMID- 15506325
TI  - Acute presentation of a solid pseudopapillary tumor of the pancreas.
AB  - We report a case of acute presentation of a solid pseudopapillary tumor of the
      pancreas in a young boy who had suffered a blunt abdominal trauma. Urgently
      performed CT examination and repeated ultrasound revealed a subhepatic mass,
      which gradually increased in size, but the imaging features were not specific
      enough to permit a precise diagnosis. Because signs of peritoneal irritation and
      increased circulatory instability gradually developed within the hours of
      observation, the decision was made to perform an urgent exploratory laparotomy.
      The exploration revealed a hematoperitoneum and a large hematoma-like subhepatic
      bleeding mass. Further exploration showed that this mass was a tumor arising from
      the head of the pancreas, which had ruptured on the surface. A curative
      pancreatoduodenectomy was performed. Pathohistological examination of the
      resected specimen revealed a solid pseudopapillary tumor of the pancreas, an
      extremely rare tumor predominantly occurring in adolescent girls and in young
      adult women. It has a favorable prognosis if resected radically. The boy in our
      report is feeling well 36 months after the operation.

PMID- 15506326
TI  - Transient paroxysmal dystonia as a side-effect of cisapride.

PMID- 15506327
TI  - [Discovery and significance of natriuretic peptides].

PMID- 15506328
TI  - [Structure and function of the natriuretic peptide family].

PMID- 15506329
TI  - [Signaling through natriuretic peptide receptors].

PMID- 15506330
TI  - [Tissue distributions and molecular forms of natriuretic polypeptides].

PMID- 15506331
TI  - [Regulation of natriuretic peptide gene expression].

PMID- 15506332
TI  - [Analysis of physiological roles of natriuretic peptides using transgenic
      animals].

PMID- 15506333
TI  - [Cardiovascular significance of the natriuretic peptide receptor, guanylyl
      cyclase-A, from studies using genetically engineered mice].

PMID- 15506334
TI  - [Morphology of atrial natriuretic peptide].

PMID- 15506335
TI  - [Measurement of natriuretic peptides].

PMID- 15506336
TI  - [Significant roles of natriuretic peptides in vascular physiology].

PMID- 15506337
TI  - [Role of natriuretic peptides in blood pressure regulation].

PMID- 15506338
TI  - [Growth promoting effect of natriuretic peptides on bones formed through
      endochondral ossification].

PMID- 15506339
TI  - [Cardioprotective effects of natriuretic peptides].

PMID- 15506340
TI  - [Diuretic and renoprotective effects of natriuretic peptides].

PMID- 15506341
TI  - [Natriuretic peptides and the endocrine system].

PMID- 15506342
TI  - [Central action of natriuretic peptides].

PMID- 15506343
TI  - [Natriuretic peptides in patients with heart failure].

PMID- 15506344
TI  - [Natriuretic peptides in patients with ischemic heart disease].

PMID- 15506345
TI  - [Natriuretic peptides and valvular heart disease].

PMID- 15506346
TI  - [Natriuretic peptides and cardiomyopathy].

PMID- 15506347
TI  - [Arrhythmias and natriuretic polypeptides].

PMID- 15506348
TI  - [Acute renal failure and natriuretic peptides].

PMID- 15506349
TI  - [Chronic renal failure, nephrotic syndrome, blood dialysis].

PMID- 15506350
TI  - [Essential hypertension and natriuretic peptides].

PMID- 15506351
TI  - [Pulmonary hypertension and natriuretic peptides].

PMID- 15506352
TI  - [Natriuretic peptides and atherosclerosis].

PMID- 15506353
TI  - [Shock and natriuretic peptides].

PMID- 15506354
TI  - [Adrenal disorders and natriuretic peptides].

PMID- 15506355
TI  - [Etiological significance of natriuretic peptides in diabetes insipidus and
      SIADH].

PMID- 15506356
TI  - [Natriuretic peptides in liver cirrhosis and their clinical implication].

PMID- 15506357
TI  - [Involvement of natriuretic peptides in pathophysiology of maternal and fetal
      disorders during pregnancy].

PMID- 15506358
TI  - [Therapeutic application of ANP: past and future].

PMID- 15506359
TI  - [Present and future of BNP].

PMID- 15506360
TI  - [Current status and future prospects of C-type natriuretic peptide].

PMID- 15506361
TI  - [Translational research on the natriuretic peptide system].

PMID- 15506362
TI  - [Renin-angiotensin-aldosterone system and natriuretic peptide system--reference
      to cardiovascular diseases].

PMID- 15506363
TI  - [Clinical development of drugs related to natriuretic peptides].

PMID- 15506364
TI  - [Discovery and significance of adrenomedullin].

PMID- 15506365
TI  - [Structure, gene and biosynthesis of adrenomedullin].

PMID- 15506366
TI  - [Adrenomedullin receptor and its signal transduction].

PMID- 15506367
TI  - [Adrenomedullin, its distribution and regulation of production].

PMID- 15506368
TI  - [Transcriptional regulation of the adrenomedullin gene].

PMID- 15506369
TI  - [PAMP: novel hypotensive peptide derived from adrenomedullin precursor].

PMID- 15506370
TI  - [Adrenomedullin-knockout mouse].

PMID- 15506371
TI  - [Localization and possible function of adrenomedullin in human tissues].

PMID- 15506372
TI  - [Immunoassays for adrenomedullin and PAMP].

PMID- 15506373
TI  - [Adrenomedullin: vascular action].

PMID- 15506374
TI  - [Protective effects of antioxidants against cardiovascular damage].

PMID- 15506375
TI  - [Effects of adrenomedullin on NO release].

PMID- 15506376
TI  - [Effect of adrenomedullin on cardiac myocytes and fibroblasts].

PMID- 15506378
TI  - [Effects of adrenomedullin on gastrointestinal and pancreatic functions].

PMID- 15506377
TI  - [Renal actions and renoprotective role of adrenomedullin].

PMID- 15506380
TI  - [The adrenomedullin family and sympathoadrenal system].

PMID- 15506379
TI  - [Adrenomedullin in the central nervous system].

PMID- 15506381
TI  - [Adrenomedullin in adipose tissue].

PMID- 15506382
TI  - [Adrenomedullin in essential hypertension].

PMID- 15506383
TI  - [Adrenomedullin in pulmonary hypertension].

PMID- 15506384
TI  - [Adrenomedullin in heart failure].

PMID- 15506385
TI  - [Pathophysiological and clinical implications of adrenomedullin in patients with
      chronic renal failure].

PMID- 15506386
TI  - [Role of adrenomedullin in septic shock].

PMID- 15506387
TI  - [Atherosclerosis and adrenomedullin].

PMID- 15506388
TI  - [Pheochromocytoma].

PMID- 15506389
TI  - [Translational research on adrenomedullin].

PMID- 15506390
TI  - [Combined therapy with adrenomedullin and cell transplantation].

PMID- 15506391
TI  - [Potential of adrenomedullin as a therapeutic tool for left ventricular
      remodeling after myocardial infarction].

PMID- 15506392
TI  - [Clinical application of adrenomedullin to therapeutic angiogenesis].

PMID- 15506393
TI  - [Discovery of ghrelin and its physiological significance].

PMID- 15506394
TI  - [Structure of ghrelin].

PMID- 15506395
TI  - [Structure-activity relationship of ghrelin].

PMID- 15506396
TI  - [Ghrelin receptor and its signal transduction].

PMID- 15506397
TI  - [Distribution of ghrelin producing-cells and regulation of their biosynthesis].

PMID- 15506398
TI  - [Mechanism of ghrelin gene expression].

PMID- 15506399
TI  - [Genetically engineered mouse models in the ghrelin gene].

PMID- 15506400
TI  - [Transgenic rat expressing growth hormone secretagogue receptor antisense].

PMID- 15506401
TI  - [Histological characteristics of ghrelin cells].

PMID- 15506402
TI  - [Ghrelin measurement].

PMID- 15506403
TI  - [Ghrelin and neuronal networks].

PMID- 15506404
TI  - [Feeding regulation by ghrelin].

PMID- 15506405
TI  - [Ghrelin and gut motility].

PMID- 15506406
TI  - [Neuroendocrine effects of ghrelin].

PMID- 15506407
TI  - [Modulation of sympathetic activity by ghrelin in the central nervous system].

PMID- 15506408
TI  - [Effects of ghrelin in aged subjects].

PMID- 15506409
TI  - [Renal effects of ghrelin].

PMID- 15506410
TI  - [Ghrelin and bone metabolism].

PMID- 15506411
TI  - [Ghrelin in the regulation of glucose and lipid metabolism].

PMID- 15506412
TI  - [Role of ghrelin in fetuses and neonates].

PMID- 15506413
TI  - [Ghrelin and cardiovascular disease].

PMID- 15506414
TI  - [Stomach disease and ghrelin].

PMID- 15506415
TI  - [Gastrectomy].

PMID- 15506416
TI  - [Role of ghrelin in anorexia nervosa].

PMID- 15506417
TI  - [Roles of ghrelin in growth and aging].

PMID- 15506418
TI  - [Obesity and diabetes mellitus].

PMID- 15506419
TI  - [Role of ghrelin in cancer].

PMID- 15506420
TI  - [Translational research of ghrelin in endocrine and metabolic diseases].

PMID- 15506421
TI  - [Ghrelin in the treatment of cardiovascular disease].

PMID- 15506422
TI  - [Ghrelin-related drugs: clinical perspectives].

PMID- 15506423
TI  - [Discovery and significance of NO].

PMID- 15506424
TI  - [Mechanisms of nitric oxide production].

PMID- 15506425
TI  - [Molecular structure, regulatory mechanism and biological activity of endothelial
      nitric oxide synthase].

PMID- 15506426
TI  - [Gene, regulation of synthesis, and physiological activity of nNOS].

PMID- 15506427
TI  - [Expression and functions of inducible nitric oxide synthase].

PMID- 15506428
TI  - [Signal transduction system of nitric oxide].

PMID- 15506429
TI  - [Mice lacking the eNOS gene].

PMID- 15506430
TI  - [Transgenic mice overexpressing the eNOS gene].

PMID- 15506431
TI  - [Nitric oxide and shear stress].

PMID- 15506432
TI  - [Nitric oxide and redox regulation].

PMID- 15506433
TI  - [Vasodilatation by nitric oxide].

PMID- 15506434
TI  - [Inhibitory effect of nitric oxide on oxidation of low-density lipoprotein].

PMID- 15506435
TI  - [Inhibition of VSMC proliferation by nitric oxide].

PMID- 15506436
TI  - [Role of nitric oxide/cGMP system in platelet function].

PMID- 15506437
TI  - [Anti-thrombotic effect of nitric oxide].

PMID- 15506438
TI  - [Cardio-protective effects of nitric oxide].

PMID- 15506439
TI  - [NO and angiogenesis].

PMID- 15506440
TI  - [Role of NO in essential hypertension].

PMID- 15506441
TI  - [Nitric oxide and pulmonary hypertension].

PMID- 15506442
TI  - [Nitric oxide and heart failure].

PMID- 15506443
TI  - [Nitric oxide and coronary spasm].

PMID- 15506444
TI  - [Cerebral ischemia and free radical].

PMID- 15506445
TI  - [Septic shock and NO].

PMID- 15506446
TI  - [NO and atherosclerosis].

PMID- 15506447
TI  - [Diabetic macroangiopathy and NO].

PMID- 15506448
TI  - [Asymmetric dimethylarginine and endothelial dysfunction].

PMID- 15506449
TI  - [Enhancement of NO bioavailability by ACEI and ARB].

PMID- 15506450
TI  - [Calcium channel blockers increasing coronary blood flow via NO-dependent
      mechanism].

PMID- 15506451
TI  - [Discovery of endothelin and its significance].

PMID- 15506452
TI  - [Gene, molecular structure, and biosynthesis of the endothelin system].

PMID- 15506453
TI  - [Endothelin receptor and intracellular signaling].

PMID- 15506454
TI  - [Regulation of endothelin-1 gene expression].

PMID- 15506455
TI  - [Endothelin gene-manipulated animals].

PMID- 15506456
TI  - [Rodent models with genetically altered endothelin receptor gene].

PMID- 15506457
TI  - [Role of endothelin in morphologenesis].

PMID- 15506458
TI  - [Vascular action of endothelin].

PMID- 15506459
TI  - [Mitogenic action of endothelin on fibroblasts].

PMID- 15506460
TI  - [Role of endothelin in the development of cardiac hypertrophy].

PMID- 15506461
TI  - [Endothelin in cardiac injury].

PMID- 15506462
TI  - [Effects of endothelin on renal function].

PMID- 15506463
TI  - [Macrophage stimulating action of endothelin].

PMID- 15506464
TI  - [Physiological and pathophysiological roles of the endothelin converting
      enzymes].

PMID- 15506465
TI  - [Endothelin and essential hypertension].

PMID- 15506466
TI  - [Pathophysiological significance of endothelin in pulmonary hypertension].

PMID- 15506467
TI  - [Endothelin and heart failure].

PMID- 15506468
TI  - [Endothelin and kidney disease].

PMID- 15506469
TI  - [Septic shock and endothelin].

PMID- 15506470
TI  - [Endothelin-1 and arteriosclerosis].

PMID- 15506471
TI  - [Endothelin-secreting tumors].

PMID- 15506473
TI  - [Discovery and clinical implications of urotensin II].

PMID- 15506472
TI  - [Prospects for endothelin-related drugs].

PMID- 15506474
TI  - [Genes, structures, and biosynthesis of urotensin II].

PMID- 15506475
TI  - [Urotensin receptors and urotensin-mediated signal transduction].

PMID- 15506476
TI  - [Tissue distribution and secretory regulation of urotensin].

PMID- 15506477
TI  - [Measurement of urotensin].

PMID- 15506479
TI  - [Autocrine/paracrine role of urotensin II as a growth factor].

PMID- 15506478
TI  - [Vasoconstrictive action of urotensin II].

PMID- 15506480
TI  - [Effects of urotensin II on platelets].

PMID- 15506481
TI  - [Urotensin II: biological action on the kidney].

PMID- 15506482
TI  - [Urotensin II and cardiac disease].

PMID- 15506483
TI  - [Possible involvement of urotensin II in essential hypertension].

PMID- 15506484
TI  - [Overview of clinical applications of urotensin II].

PMID- 15506485
TI  - [Urotensin-related peptide--urocortin].

PMID- 15506486
TI  - [Development of therapeutic agents related to urotensin II].

PMID- 15506487
TI  - [Basic and clinical research in dry eye syndrome].

PMID- 15506488
TI  - [The effect of growth factors on the proliferation of cultured porcine trabecular
      meshwork cells].
AB  - PURPOSE: We attempted to identify cell growth factors that cause a multiplication
      of trabecular meshwork(TM) cells. METHODS: Porcine TM cells were cultured in
      Dulbecco's modified Eagle's medium/nutrient mixture F-12/Ham to which we added 1,
      10, and 100 ng/ml of platelet-derived growth factor(PDGF), fibroblast growth
      factor 2(FGF2), insulin-like growth factor-1 (IGF-1), vascular endothelial cell
      growth factor(VEGF), hepatocyte growth factor (HGF), or brain-derived
      neurotrophic factor(BDNF). We measured [3H] thymidine incorporation to evaluate
      the influence of the growth factors on TM cell proliferation. RESULTS: [3H]
      thymidine incorporation into TM cells was promoted by 10 and 100 ng/ml of PDGF,
      IGF-1, and FGF2 after 24 and 48 hours, whereas 1, 10, and 100 ng/ml of VEGF
      restrained cell proliferation after 48 hours. HGF and BDNF did not show any
      remarkable influence on TM cell proliferation. CONCLUSIONS: Our, results suggest
      that PDGF, IGF-1, and FGF2 may cause a drop in intraocular pressure followed by
      activation of a TM function, by multiplying TM cells.

PMID- 15506489
TI  - [The usefulness of frequency doubling technology perimetry in glaucoma screening
      in health-check program].
AB  - PURPOSE: Visual field testing has not been used as a screening procedure because
      it requires too much testing time and manpower. We evaluated the usefulness of
      Frequency Doubling Technology(FDT) visual field testing as a screening procedure
      for glaucoma in a health-check screening program. METHODS: A total of 800 eyes of
      400 persons were examined for visual acuity, noncontact tonometry, slit-lamp
      biomicroscopy, funduscopy, and FDT testing of visual fields (N-30-5). The initial
      screening result was considered positive for glaucoma if any abnormality of FDT
      perimetry was detected, the intraocular pressure exceeded 21 mmHg, or funduscopy
      showed glaucomatous disc cupping or retinal nerve fiber layer defect. The re
      examination comprised several ophthalmic examinations such as automatic perimetry
      9 Humphrey field analyzer). RESULTS: Glaucoma was suspected in 118 eyes; 16 eyes
      were thus diagnosed after re-examination. FDT detected visual field abnormalities
      in 15 eyes. There were 40 eyes that were not diagnosed although FDT detected
      visual field abnormalities. CONCLUSIONS: FDT detected visual field abnormalities
      in glaucoma patients with high sensitivity and specificity. FDT is a useful
      screening test for glaucoma.

PMID- 15506490
TI  - [New surgical methods for punctal occlusion of severe tear-deficient dry eye and
      its outcome].
AB  - PURPOSE: Although several surgical methods for punctal occlusion have been
      reported, it is difficult to obtain complete punctal occlusion in all cases since
      recanalization of the punctum often occurs after the operation. In this report,
      new surgical procedures to obtain sufficient occlusion of punctum are introduced
      and the outcome of the present method is compared with that of previous methods.
      SUBJECTS AND METHODS: Subjects were 33 severe tear-deficient dry eye patients (4
      males and 29 females; mean age: 54.3 yrs.) and they were considered as candidates
      for punctal occlusion of both upper and lower puncta. The previous surgical
      punctal occlusion method had been performed in 12 cases (group A: 10 females and
      2 males) and the newly-developed method was applied to 21 cases (group B : 19
      females and 2 males). Corneal epithelial damage(scored with AD classification; A
      : area, D : density, scored from 0 to 3) was compared before and after the
      treatment and the control-lability of dry eye with only an artificial tear
      preparation was compared between the previous and the new methods. The newly
      developed surgical procedures include the following steps: (1) diathermy of the
      epithelium of the canaliculus using a newly-designed electric needle for
      diathermy, (2) full removal of the epithelium of the canaliculus using a hand
      motor drill, (3) cutting the punctum at two opposite points parallel to the lid
      margin, (4) suturing the punctum to close the cut punctum with 10-0 nylon or 8-0
      absorbable sutures. RESULTS: In group A, corneal epithelial damage improved a
      little from A, D : 2.4, 2.1 to A, D: 1.8, 1.9 during an average of 7.2 months of
      alone follow-up, and only 2 of the 12 cases obtained control with eye drops. In
      group B, the corneal epithelial damage improved significantly from A, D : 2.1,
      2.2 to A, D : 1.0, 1.3 during an average of 8.2 months of follow-up, and all
      cases obtained control with eye drops alone. CONCLUSION: The new surgical methods
      are regarded as a more complete way of performing surgical punctal occlusion
      compared to previous methods.

PMID- 15506491
TI  - [Bilateral retinal detachment after laser in situ keratomileusis].
AB  - BACKGROUND: We report a case of bilateral retinal detachment after laser in situ
      keratomileusis(LASIK). CASE: A 49-year-old man received multiple laser
      photocoagulation for retinal lattice degeneration in both eyes and retinal tears
      in the left eye. He underwent bilateral LASIK in another country about 6 months
      after the laser photocoagulation. After the LASIK his eyes showed bilateral
      retinal detachment, 2 weeks later in the right eye and 5 months later in the left
      eye. We had to perform retinal detachment surgery four times, scleral buckling,
      vitrectomy, silicone oil tamponade, and removal of the silicone oil for the right
      eye, and one scleral buckling procedure for the left eye to achieve retinal
      attachment. Soon after each retinal surgery, we recognized diffuse flap edema and
      interface haze, three times in the right cornea and one time in the left,
      although this corneal flap edema subsided without any sequel. CONCLUSION: In this
      case, laser photocoagulation had been done several times to prevent retinal
      detachment in both eyes. However, retinal detachment occurred 2 weeks after LASIK
      in the right eye, and therefore, the LASIK procedure was considered to be the
      main factor influencing the development of the retinal detachment. The left eye
      showed retinal detachment 5 months after LASIK and we thought it possible that
      this retinal detachment occurred as a natural consequence of myopia. We believe
      it is important to hava a thorough funduscopic examination done before LASIK and
      it is necessary to pay attention to corneal edema and interface haze after
      retinal detachment surgery for post-LASIK patients.

PMID- 15506492
TI  - [Induction and isolation of embryonic stem cell-derived cradiomyocytes].

PMID- 15506493
TI  - [The molecular bases of inherited skin color diseases].

PMID- 15506494
TI  - [A study of the difference in intestinal adaptation between the residual jejunum
      and the ileum in rats with short bowel syndrome].
AB  - OBJECTIVES: Controversy remains regarding which residual segment, namely the
      jejunum or ileum, is more beneficial for intestinal adaptation in patients with
      short bowel syndrome (SBS). The aim of our study is to evaluate the residual
      intestinal adaptation after a massive small intestinal resection and thereby
      determine which of the two residual segments demonstrates a better intestinal
      adaptation. METHODS: The SBS rats underwent about a 70% resection of either the
      jejunum or ileum, respectively. Sham rats underwent an ileal transection with a
      subsequent reanastomosis of the same portion. The body weight was measured every
      day after the operation. Two weeks after the operation, all rats were sacrificed.
      The intestinal length, the hematological and serum chemical data, and the
      histological findings of the residual intestine were investigated in all rats to
      evaluate the intestinal adaptation. RESULTS: The body weight gain in the rats
      with the residual ileum (ileum group) was similar to that of the Sham group and
      better than that of the rats with residual jejunum (jejunum group). The length of
      the residual intestines in the jejunum group was longer than that in both the
      sham and ileum groups. Regarding hematological and serum chemical studies, the
      jejunum group tended to demonstrate more anemia and malnutrition than both the
      sham and ileum groups. In a histological study, the villous height in both the
      jejunum and ileum groups was significantly larger than in the preoperative
      condition. In both groups, the degree of crypt depth only significantly increased
      in the ileum group in comparison to the preoperative condition. Regarding the
      thickness of the muscular layers, a no difference was observed among all groups.
      CONCLUSION: Based on our data, in patients with SBS, the use of the residual
      ileum was therefore found to be preferable to that of the residual jejunum
      regarding intestinal adaptation.

PMID- 15506495
TI  - Auditory research at Walter Reed Army Medical Center.

PMID- 15506496
TI  - Predicting success with hearing aids in everyday living.
AB  - Persons with impaired hearing who are candidates for amplification are not all
      equally successful with hearing aids in daily living. Having the ability to
      predict success with amplification in everyday life from measures that can be
      obtained during an initial evaluation of the patient's candidacy would result in
      greater patient satisfaction with hearing aids and more efficient use of clinical
      resources. This study investigated the relationship between various demographic
      and audiometric measures, and two measures of hearing aid success in 50 hearing
      aid wearers. Audiometric predictors included measures of audibility and
      suprathreshold distortion. The unaided and aided signal-to-noise ratio (SNR) loss
      on the QuickSIN test provided the best predictors of hearing aid success in daily
      living. However, much of this predictive relationship appeared attributable to
      the patient's age.

PMID- 15506497
TI  - Relationship between laboratory measures of directional advantage and everyday
      success with directional microphone hearing aids.
AB  - The improvement in speech recognition in noise obtained with directional
      microphones compared to omnidirectional microphones is referred to as the
      directional advantage. Laboratory studies have revealed substantial differences
      in the magnitude of the directional advantage across hearing-impaired listeners.
      This investigation examined whether persons who were successful users of
      directional microphone hearing aids in everyday living tended to obtain a larger
      directional advantage in the test booth than persons who were unsuccessful users.
      Results revealed that the mean directional advantage did not differ significantly
      between patients who used the directional mode regularly and those who reported
      little or no benefit from directional microphones in daily living and, therefore,
      tended to leave their hearing aids set in the default omnidirectional mode.
      Success with directional microphone hearing aids in everyday living, therefore,
      cannot be reliably predicted by the magnitude of the directional advantage
      obtained in the clinic.

PMID- 15506498
TI  - Predicting hearing aid microphone preference in everyday listening.
AB  - Seventeen hearing-impaired adults were fit with omnidirectional/directional
      hearing aids, which they wore during a four-week trial. For each listening
      situation encountered in daily living during a total of seven days, participants
      selected the preferred microphone mode and described the listening situation in
      terms of five environmental variables, using a paper and pencil form. Results
      indicated that hearing-impaired adults typically spend the majority of their
      active listening time in situations with background noise present and surrounding
      the listener, and the signal source located in front and relatively near.
      Microphone preferences were fairly evenly distributed across listening situations
      but differed depending on the characteristics of the listening environment. The
      omnidirectional mode tended to be preferred in relatively quiet listening
      situations or, in the presence of background noise, when the signal source was
      relatively far away. The directional mode tended to be preferred when background
      noise was present and the signal source was located in front of and relatively
      near the listener. Results suggest that knowing only signal location and distance
      and whether background noise is present or absent, omnidirectional/directional
      hearing aids can be set in the preferred mode in most everyday listening
      situations. These findings have relevance for counseling patients when to set
      manually switchable omnidirectional/directional hearing aids in each microphone
      mode, as well as for the development of automatic algorithms for selecting
      omnidirectional versus directional microphone processing.

PMID- 15506499
TI  - Kentucky's pain.

PMID- 15506500
TI  - A new style in the operating room.

PMID- 15506501
TI  - The war we haven't won.

PMID- 15506502
TI  - Healthcare's minority report. Sullivan Commission, IOM try to make patient,
      hospital staff makeup more reflective of the nation's ever-changing population.
AB  - Properly caring for patients in a nation with changing demographics means the
      healthcare workforce needs more diversity, according to a new report from a
      commission led by former HHS Secretary Louis Sullivan, left. Among the
      recommendations are boosting minority scholarships for health and medical
      education.

PMID- 15506503
TI  - Lucrative liaison? Critics question VHA foundation-Novation connection.

PMID- 15506504
TI  - Defensive blow. MedAssets arm hits Guidant with counterclaim.

PMID- 15506505
TI  - Unfulfilled potential. More performance pay would improve care: NCQA.

PMID- 15506506
TI  - Veto power. Bill mandating discounts for uninsured gets spiked.

PMID- 15506507
TI  - Not so fast. Moody's cautions hospitals on alternative investments.

PMID- 15506508
TI  - A dip is just a dip. PPI, CPI indicate healthcare costs are on the rise.

PMID- 15506509
TI  - Looking outside for IT. Stanford outsources to help upgrade system.

PMID- 15506510
TI  - Patients' blueprint. NIH patients help map out new clinical center.

PMID- 15506511
TI  - New requirements. Home-care reporting may expand.

PMID- 15506512
TI  - Skepticism builds. GAO raises questions about outpatient rehab.

PMID- 15506513
TI  - Discounting and counting. Mass. hospitals join trend of linking breaks,
      collections.

PMID- 15506514
TI  - Quality reporting is no game. Initiatives suffer from providers' ability to walk
      away if they aren't winning.

PMID- 15506515
TI  - Fiddling while Rome burns. Industry focus on 'slowing' health-cost rise ignores
      looming disaster.

PMID- 15506516
TI  - Outsiders moving in. Annual survey shows outsourcing remains a growth industry,
      with more hospitals preferring to buy services by the bundle.

PMID- 15506517
TI  - Stretching the limits: Calif. Children's Hospital uses tech to monitor its
      inventory of beds, letting it increase capacity without actually adding any more
      beds.

PMID- 15506518
TI  - Genetic medicine at the RNA level: modifications of the genetic repertoire for
      therapeutic purposes by pre-mRNA trans-splicing.
AB  - Gene therapy is conventionally carried out by transferring genetic material to
      the target cell where the exogenous gene is expressed using the endogenous
      transcription and translation machinery in parallel with the target cell genome.
      This review focuses on a new paradigm of gene therapy, the use of trans-splicing
      to modify the genetic repertoire at the pre-mRNA level to treat genetic and
      acquired disorders. Therapeutic trans-splicing can be used to alter coding
      domains, to create novel fusion proteins, to direct gene products to various
      cellular compartments, and to overcome some of the limitations to vector-derived
      gene transfer technology, including gene therapy with large genes or with genes
      coding for toxic proteins. To demonstrate the potential of therapeutic trans
      splicing, eukaryotic cis-splicing and trans-splicing are reviewed, followed by a
      discussion of strategies of therapeutic pre-mRNA trans-splicing directed by
      exogenous gene transfer.

PMID- 15506520
TI  - Neural reapportionment: an hypothesis to account for the function of sleep.
AB  - Sleep is a ubiquitous component of animal life, and prolonged sleep deprivation
      is fatal in both vertebrates and invertebrates. The physiologic function of
      sleep, however, is not known. We propose here that sleep provides a period of
      time necessary to reapportion resources within neurons and neural systems that
      become sub-optimally distributed during active waking. Three specific examples of
      such reapportionment during sleep are suggested: (1) the return of the
      neurotransmitter, glutamate, to synaptic vesicles at presynaptic sites most
      active during waking, (2) the intracellular movement of mitochondria from
      neuronal processes to the cells soma where mitochondrial replication can occur,
      and (3) the readjustment of the level and distribution of neurotransmitters
      within the brainstem modulatory systems and elsewhere that must function in an
      integrated fashion during waking. Experimental approaches that might be utilized
      to test these hypotheses are suggested.

PMID- 15506519
TI  - [Glucose 6-phosphate dehydrogenase deficiency: a protection against malaria and a
      risk for hemolytic accidents].
AB  - Glucose 6-phosphate dehydrogenase (G6PD) catalyses the first step of the pentose
      phosphate pathway, which in the RBC leads to the formation of NADPH, essential to
      prevent the cell from an oxidative stress. Worldwide, more than 400 million
      people (90% being males) are affected by G6PD deficiency, in regions that are, or
      have been, endemic for malaria and in populations originating from these regions.
      RBCs with low G6PD activity offer a hostile environment to parasite growth and
      thus an advantage to G6PD deficiency carriers. The counterpart of this protective
      effect is an increased susceptibility to oxidants such as some foods (fava
      beans), drugs (anti-malarial or sulphonamides), or various chemicals. In the case
      of G6PD deficiency, the hypothesis of a convergent evolution between parasite,
      protecting mutation, and cultural traditions (food, skin painting...) has been
      proposed. Near to 150 different G6PD variants have been described, which are
      classified into four types, according to their clinical effects. Several
      variants, such as the G6PD A- or the Mediterranean variant, reach the
      polymorphism level in endemic regions. The recent determination of the three
      dimensional structure of this enzyme allows one to explain now the mechanisms of
      the disorders in terms of structure-function relationship.

PMID- 15506521
TI  - Oxygen and nitrogen isotopic fractionations during human respiration.
AB  - Both oxygen and nitrogen isotope compositions (delta18O and delta15N) of exhaled
      air from 10 individuals were measured. Results show linear relations between
      isotope variation and the fraction of O2 used during the respiration process. The
      isotopic influence of physiological parameters such as smoking habits, age,
      haemoglobin count, oxygen fixation rate or physical exercise was assessed. Among
      them, only smoking habits do not have any effect on delta18O. Delta15N
      differences between inhaled and exhaled air may indicate an active (but minor)
      role for nitrogen during the human respiration process. Nevertheless, nitrogen
      fractionation is homogenous among all the individuals, which is coherent with the
      fact that nitrogen metabolism is controlled by the intestinal bacterial activity.

PMID- 15506522
TI  - Light and scanning electron microscopy of the cardiac gland region of the stomach
      of the babirusa (Babyrousa babyrussa--Suidae, Mammalia).
AB  - Previous studies have indicated that the gross anatomical structure of the
      stomach of the babirusa (Babyrousa babyrussa) differs markedly from that of all
      other pigs. This light and scanning electron microscopic study revealed a
      previously unknown, microscopic structure characterised by a 'honeycomb' pattern
      at the luminal surface of the tunica mucosa. The walls of the 'honeycomb' were
      about 0.20-0.25 mm high and appeared almost entirely composed of various types of
      bacteria. Underneath the bacteria the walls were formed by thin tubes composed of
      non-glandular squamous epithelial-like cells, extending from the tops of the
      ridges between each glandular pit. There is as yet no evidence of a comparable
      structure in the stomach of any other pig, or to our knowledge any other
      forestomach-fermenting mammal.

PMID- 15506523
TI  - [Evaluation of the resistance to two nematodes: Radopholus similis and
      Meloidogyne spp. in four banana genotypes in Morocco].
AB  - Radopholus similis and Meloidogyne spp. are the main nematode parasites of banana
      plants grown under plastic shelters in Morocco. A test was made in pots to
      evaluate the resistance of four genotypes of banana to these nematodes. Infection
      by Meloidogyne spp. brought about an increase in root weight in all banana plants
      tested because of gall formation. The inoculation of R. similis produced a
      reduction in length and diameter of the pseudo-trunk as well as in root and
      aerial mass in all genotypes. Pisang jari buaya showed the significantly lowest
      number of Meloidogyne nematodes per 10 g of roots, whereas for R. similis, the
      significantly smallest numbers were obtained in Pisang berlin and Pisang jari
      buaya. Therefore, Pisang jari buaya was the only banana genotype studied to show
      some degree of resistance to both nematodes.

PMID- 15506524
TI  - Factors influencing the spatio-temporal distribution of benthic Microcystis
      aeruginosa colonies (Cyanobacteria) in the hypertrophic Grangent Reservoir
      (Loire, France).
AB  - The spatio-temporal distribution of benthic colonies of Microcystis aeruginosa in
      Grangent Reservoir (France) in 2000 was not homogeneous and appeared to be
      controlled by many external factors: lake depth, station morphometry, substratum
      and hydraulic regime (lacustrine or fluvial). A most important concentration of
      benthic colonies was found at deep sites with fine sediment or at sites where the
      sediment was rich in organic matter. In spite of a stable water level and a
      minimum flow during summer, the number of benthic colonies showed great variation
      in the lacustrine downstream part of the reservoir. These variations may be
      explained by the dynamics of planktonic cyanobacteria.

PMID- 15506525
TI  - Regulation of the number of spiders participating in collective prey transport in
      the social spider Anelosimus eximius (Araneae, Theridiidae).
AB  - In an experimental study, mechanisms by which cooperative prey transport is
      achieved in social spiders were clarified. Factors that could influence the
      number of individuals that participate in prey transport (prey mass, length and
      vibration) were investigated. Results show that two factors are fundamental: the
      vibrations and the prey length. Prey mass did not seem to influence spiders'
      participation. Thus, the single fact that individuals respond locally to
      environmental stimuli (intensity of vibration, available site on the prey)
      explains how spiders cooperate and efficiently capture a wide range of prey types
      without complex communication systems.

PMID- 15506526
TI  - Poll results: doctors' disruptive behavior disturbs physician leaders.
AB  - Results of ACPE's 2004 Physician Behavior Survey show that physician executives
      face deep frustrations when forced to tackle the thorny issue of disruptive
      behavior by fellow physicians.

PMID- 15506527
TI  - For safety's sake disruptive behavior must be tamed.

PMID- 15506528
TI  - Managing unmanageable physicians: leadership, stewardship and disruptive
      behavior.
AB  - Physician executives would undoubtedly prefer to spend the bulk of their time
      inspiring great employees and building productive teams instead of struggling
      with disruptive physician behavior. Explore ways to diminish the frequency and
      intensity of disruptive behavior in your organization and identify your role,
      rights, responsibilities and accountabilities as a physician leader.

PMID- 15506529
TI  - R-E-S-P-E-C-T: bedrock of satisfaction and effectiveness for organizations and
      individuals.

PMID- 15506530
TI  - Disruptive behavior and the law.

PMID- 15506531
TI  - Doctors doing drugs and drinking.
AB  - Meet Dr. Kevin, Dr. Bob and Dr. Robert, three physicians whose behavior problems
      included doing drugs or drinking. All three got sober, but their struggles with
      substance abuse still haunt them today.

PMID- 15506532
TI  - Misbehaving physicians and professional ethics.
AB  - Consider a true story about physician misbehavior and see how it was handled.
      Sometimes a gentle touch works well in situations of unexpected and unintended
      behavioral problems.

PMID- 15506534
TI  - Spinning a winning web: attracting and retaining top performers.
AB  - There are steps you can take right now to improve your organization's working
      environment and help attract top-drawer candidates who may be less likely to
      exhibit behavior problems.

PMID- 15506533
TI  - Understanding emotional intelligence can help alter problem behavior.
AB  - Self-awareness is key to better understanding behavior. Discover how emotional
      intelligence drives behavior and can be learned to improve ineffective behaviors.

PMID- 15506535
TI  - Push and pull: resolving differences of opinion during meetings.
AB  - Consider the results of a recent study that looks at how to handle differences of
      opinions among physicians and other health care staff, including the ways that
      "push" and "pull" statements affect the outcomes of meetings.

PMID- 15506536
TI  - Reality check: is your behavior aligned with organizational goals?
AB  - Strong, well thought out organizational behaviors help instill confidence in
      patients and allow physicians to take a leadership role in health care.

PMID- 15506538
TI  - Get her to the OR, she's herniating!

PMID- 15506537
TI  - Case study: using control charts to track physician productivity.
AB  - Learn how control charts are being used to gauge physician productivity in a
      Shriners hospital in Kentucky. The charts provide a fair and accurate analysis
      that doctors appreciate.

PMID- 15506539
TI  - The four questions to ask about your organization.

PMID- 15506540
TI  - Reviewing your physician compensation plan.

PMID- 15506541
TI  - The role of the physician executive in negotiation.

PMID- 15506542
TI  - Career management: characteristics of a sophisticated job candidate--Part II.

PMID- 15506543
TI  - Pandemic influenza preparedness.

PMID- 15506544
TI  - Ibuprofen and Alzheimer's disease.
AB  - There is epidemiological observation that long-term treatment of patients
      suffering from rheumatoid arthritis with ibuprofen results in reduced risk and
      delayed onset of Alzheimer's disease (AD). Chronic central nervous system
      inflammation in AD brain is implicated in the pathology, but how ibuprofen
      impacts the pathogenic AD pathways is unclear. Ibuprofen, a commonly used over
      the-counter nonsteroidal anti-inflammatory drug (NSAID) that is a cyclooxygenase
      (COX)-1 and COX-2 inhibitor as well as a peroxisome proliferator-activated
      receptor (PPAR) agonist, decreases the production of nitric oxide (NO), protects
      neurons against glutamate toxicity and decreases the production of
      proinflammatory cytokines. Ibuprofen crosses the blood brain barrier and
      suppresses neuritic plaque pathology and inflammation in AD brain. Furthermore,
      ibuprofen is a potent free radical scavenger, and it could reduce lipid
      peroxidation and free radical generation. Because of neuroprotective activity,
      relative safety, and its long history of use, ibuprofen is currently being
      developed for clinical use in AD. Ibuprofen may be a promising new therapeutic
      avenue for the treatment of neurodegenerative diseases such as AD.

PMID- 15506545
TI  - Growth factors--importance and possibilities for enhancement of the healing
      process in bone fractures.
AB  - The healing process after bone fractures is subject to complex regulation. A
      major part in it is played by biologically active molecules, called growth
      factors. The most important of these are the bone morphogenetic proteins (BMPs),
      transforming growth factor--beta (TGF-beta), platelet-derived growth factor
      (PDGF), fibroblast growth factor (FGF), insulin-like growth factor (IGF),
      vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF).
      AIM: The aim of the present study was to do a short review of data in the
      scientific literature about the specific role of each factor in reparative
      osteogenesis in relation to the healing of bone fractures, as well as the
      possibilities for enhancement of this process by growth factors. MATERIAL AND
      METHODS: A detailed Medline search was conducted with emphasis on reports from
      the last ten years. CONCLUSION: The information gathered demonstrated the key
      role of growth factors and their potential for stimulation of healing of
      fractures and their complications. This conclusion is supported by results from
      numerous animal experiments.

PMID- 15506546
TI  - Topically applied vitamins and their cutaneous effects.
AB  - The number of cosmetic products which include vitamins as a constituent has
      increased three-fold since 1991. Vitamins are commonly used as ingredients of
      products designed to improve the appearance and health of the skin; for this
      reason the cutaneous benefits of such products are actively researched by
      dermatologists and chemists. The present study does a review of the action of
      topically applied vitamins for local use which improves the function of the skin.
      We specifically consider the biologic activity of topically applied vitamins,
      their stability and usefulness. Ways of stabilizing different kinds of vitamins,
      as well as their stability to oxygen, light, temperature, acids, and bases, are
      shown. The conclusion suggested by the review is that the efficiency of topically
      applied vitamins is dependent not only on their good stabilization and
      concentration but also on the clinical individual tests that can determine the
      best product for each particular patient.

PMID- 15506547
TI  - Complications in total hip replacement.
AB  - AIM: THE PURPOSE of the present study was to present the most common treatment
      failures and complications associated with total hip replacement. MATERIAL AND
      METHODS: Between 1986 and 2002, 486 total hip replacements (THR) in 403 patients
      were performed at the Clinics of Orthopedic and Trauma Surgery (St. George
      University Hospital, Plovdiv). 315 (61.8%) of the patients underwent THR for
      coxarthrosis, 171 (35.1%)--for traumatic or pathologic subcapital femoral neck
      fractures. 312 (64.2%) of the patients were women and 174 (35.8%) were men. Right
      and left arthroplasties were carried out. Patients' age was in the range of 28 to
      53 years (median age 59.6). Complications were diagnosed in 97 (19.9%). Late
      postoperative complications (53.6%) as aseptic loosening of the prosthetic
      components, superficial and deep hematogenous infections, prosthetic dislocations
      and heterotopic ossifications were predominant. RESULTS: Complications were
      categorized as intraoperative, postoperative and late--a finding, consistent with
      the data in the literature. Among the intraoperative complications most common
      were malposition of the capsule (7 patients) and of the stem (4 patients) and
      longer stem (in 1 patient), but they caused no complaints. The postoperative
      complications consisted of hematomas and seromas wich were treated with early
      revision surgery. The main causes for late complications were postoperative
      ossification in 28 patients. Aseptic loosening of the prosthesis was seen in 11
      patients. 8 of them complained of acetabular and 3 of thigh pain. Capsule
      dislocation was registered in 3 patients. CONCLUSIONS: Complications in THR are
      not infrequent. Their avoidance is largely dependent on the skill and
      qualification of the team and the quality of hospital care. Adequate risk
      assessment and prophylaxis are essential in disease outcome.

PMID- 15506548
TI  - Sarcomas of the mandible. Literature review and case reports.
AB  - Sarcomas of the maxillofacial region are rare tumors presenting with wide variety
      of histopathological and clinical features. The authors treated six patients with
      sarcomas of the mandible over a period of ten years: 2 patients with
      fibrosarcomas, 2 with lymphosarcomas, one with osteogenic sarcoma and one with
      chondrosarcoma. The patients' ages ranged from 28 to 65 years, one was male and
      five - female. The present study reports three cases (osteogenic sarcoma,
      fibrosarcoma, chondrosarcoma) with specific clinical and radiographic
      characteristics, demonstrating the differences between the various types of
      sarcomas. Special attention is paid to the first clinical signs and symptoms, and
      to the differential diagnosis with inflammatory conditions (post-extraction
      alveolitis, chronic odontogenic osteomyelitis), benign tumors
      (osteoblastoclastoma, ameloblastoma, odontogenic cysts, fibrous dysplasia) and
      centrally developing jaw carcinomas. Particular emphasis is given to CT imaging
      and morphological examinations in making an accurate diagnosis and providing
      adequate treatment. Early diagnosis and precise surgical treatment (total
      resection or hemiexarticulation, or neck dissection if submandibular or cervical
      metastases are present) are essential to achieve satisfactory management of these
      malignant neoplasms. The radiotherapy and chemotherapy administered according to
      the histologic features of the tumor are also of significance.

PMID- 15506549
TI  - Protective effect of BP 2-94, a histamine H3-receptor agonist prodrug, in a model
      of carbon tetrachloride-induced hepatotoxicity in rats.
AB  - BP 2-94 is a prodrug of the H3-receptor agonist (R)-alpha-methylhistamine [(R)
      alpha-MeHA]. BP 2-94 displayed anti-inflammatory, antinociceptive and ulcero
      protective properties in experimental animals. AIM: The aim of the present study
      was to investigate the effect of BP 2-94 in a model of carbon tetrachloride
      (CCl4)-induced hepatotoxicity in rats. MATERIALS AND METHODS: In order to
      investigate the effect of BP 2-94 it was applied to rats either alone (20, 40 and
      60 micromol kg(-1), 4 days) or as a pretreatment (20, 40 and 60 micromol kg(-1),
      4 days) before the application of CCl4 (0,2 ml kg(-1), 2 days). RESULTS: BP 2-94
      in the tested doses did not cause significant changes in the plasma aspartate
      transaminase (AST) and alanine transaminase (ALT) activities and the liver
      microscopic appearance was normal. Hepatocyte damage, as evident by local areas
      of liver necrosis and elevated levels of plasma AST and ALT, occurred in rats
      following acute exposure to CCl4 (0,2 ml kg(-1), 2 days). BP 2-94 applied as a
      pretreatment dose-dependently reduced the necrotic changes in rat liver and
      inhibited the increase of plasma AST and ALT activities in response to CCl4.
      CONCLUSIONS: BP 2-94 had a hepatoprotective effect in a model of CCl4-induced
      toxicity in rats. This effect might be due the H3-agonistic activity of its
      active metabolite (R)-alpha-MeHA.

PMID- 15506550
TI  - Effects of Tyr-MIF's family of peptides on immobilization stress-induced
      antinociception in rats.
AB  - The Tyr-MIF-1 family of peptides includes MIF-1, Tyr-MIF-1, Tyr-W-MIF-1 and Tyr-K
      MIF-1, which have been isolated from bovine hypothalamus and cortex of human
      brain. Data in the literature suggest that peptides of Tyr-MIF-1's family have
      opioid-like and anti-opioid actions. All these peptides interact with opioid
      receptors and in addition bind to non-opiate sites specific for each of the
      peptides and able to inhibit the expression of some forms of stress-induced
      analgesia (SIA) in various species. AIM: To examined the effects of the Tyr-MIF
      1's peptides on immobilization stress-induced antinociception. METHODS: Tyr-MIF
      1's peptides were given to male Wistar rats intraperitoneally before or after 1
      hour of restraint. The changes in the mechanical nociceptive threshold of the
      animals were measured by the Randall-Selitto paw pressure test. RESULTS:
      Immobilization of the rats increased the pain threshold at least 1 h. Tyr-MIF-1's
      peptides have contrasting effects on immobilization stress-induced
      antinociception in paw-pressure test in rats. When administered before
      immobilization procedure they potentiated the immobilization stress-induced
      antinociception, while if given after immobilization, they reduced it.
      Antinociceptive effects of Tyr-MIF-1, Tyr-W-MIF-1 and Tyr-K-MIF-1 were reduced in
      condition of stress. CONCLUSION: Tyr-MIF-1's peptides exerted antiopioide effects
      under condition of stress in paw-pressure test. These antiopioide effects were
      more pronounced when peptides were injected after stress exposure.

PMID- 15506551
TI  - Influence of oxytocin on the steroidogenic activity of rat adrenal cortex.
AB  - The aim of the present study was to investigate the changes in the morphology and
      3beta-hydroxysteroid dehydrogenase activity of the cells of the rat adrenal
      cortex after single and long-term in vivo treatment with oxytocin. Sexually
      mature male Wistar rats (n = 12) divided into three groups were used in the
      study. Group 1 were rats that received a single treatment with oxytocin (0.25
      IU/100g wet weight, subcutaneously); group 2 included rats that were treated with
      oxytocin (0.25 IU/100 g wet weight, subcutaneously) for a period of 10 days; and
      group 3 were the control animals treated with saline solution. The activity of
      3beta-hydroxysteroid dehydrogenase, mainly from the adrenal cortex, was examined
      on fresh cryostat sections (6 mm). Single treatment with oxytocin increased the
      enzyme activity of the adrenal cortex cells, especially in the cells of zona
      gromerulosa and zona fasciculata, while in long-term treatment inhibition of the
      enzyme activity was present. The results obtained demonstrate the changes induced
      in the enzyme activity of the adrenocorticocytes after treatment with oxytocin
      and suggest the role of this neuropeptide in the local regulation of the adrenal
      function.

PMID- 15506552
TI  - Experimental study of the morphological and electromyographic characteristics of
      the most frequent iatrogenic lesions of the recurrent laryngeal nerves in thyroid
      surgery.
AB  - INTRODUCTION: Iatrogenic lesions of the recurrent laryngeal nerves remain one of
      the most severe and frequent complications in thyroid surgery. According to
      Eisele (Laryngoscope 1996;106:443) their incidence varies between 1% and 12%
      depending on the size of surgery. AIM: The aim of the study was to examine
      experimentally the type of neural lesion and the efficiency of stimulation
      electromyography for immediate evaluation of the recurrent laryngeal nerve
      function in the most common surgical traumas. MATERIAL AND METHODS: Ten
      clinically healthy and parasite-free male dogs of mixed breed weighing from 11 to
      18 kg were used in the experiment. The injured laryngeal nerves of the
      experimental animals were examined histologically using Sudan III staining for
      myelin and Bilshovsky staining for neurofibrils. The intraoperative
      electromyography was performed with Neurostim 100. RESULTS: The results show
      severe damage both of the myelin sheath and neurofibrils in most of the surgical
      traumas of the nerve fiber. The electromyography of the laryngeal musculature
      shows complete interruption of the conduction of the action potential in all
      types of experimental lesions. CONCLUSION: EMG intraoperative monitoring of the
      laryngeal nerves appears the most effective measure to avoid the complication.

PMID- 15506553
TI  - Craniofacial fibrous dysplasia. conservative surgical management. Review of
      literature and report of a case.
AB  - The present study presents a case of craniofacial fibrous dysplasia attenuating
      the orbit and the nasal airway, which was treated by conservative surgical
      approaches. Nasal and orbital decompression, and facial recontouring were
      performed simultaneously. This was done via a transconjunctival and
      transcaruncular approaches with a lateral canthotomy, which provided access to
      the four walls of the orbit, midface and the lateral nasal wall. The reduction of
      the turbinates was done through a standard turbinectomy approach and the nasal
      decompression was done via intercartilaginous access and a full transfixion
      incision and nasal degloving. The bulk of the lesion was removed with chisels,
      gauges, and rotary instruments. The orbital debulking extended to the orbital
      apex, which was not involved by the fibrous dysplasia. Approximately 200 mg of
      dysplastic bone was removed. The functional and aesthetic results were good. The
      symptoms of chronic conjunctivitis and nasal obstruction have been alleviated and
      there is no deterioration of his condition. The symptoms of anosmia have also
      disappeared. Conservative surgical treatment of craniofacial dysplasia in adults
      with stable disease is recommended.

PMID- 15506555
TI  - Risk of vocal palsy after thyroidecitomy with identification of the recurrent
      laryngeal nerve.
AB  - The purpose of this study was to assess the risk of vocal palsy after
      thyroidectomy with identification of recurrent laryngeal nerve (RLN) during
      surgery. In all, 521 patients treated by the same surgeon were enrolled in this
      study. Temporary and permanent vocal palsy rates were analyzed for patient groups
      classified according to surgery for primary benign thyroid disease, thyroid
      cancer, Graves' disease, and reoperation. Measurement of the vocal palsy rate was
      based on the number of nerves at risk. Twenty-six intentionally sacrificed RLNs
      were excluded from analysis. Forty patients developed postoperative unilateral
      vocal palsy. Complete recovery of vocal palsy was documented for 35 of the 37
      patients (94.6%) whose RLN integrity had been ensured intraoperatively. Recovery
      from temporary vocal palsy ranged from 3 days to 4 months (mean, 30.7 days). The
      overall incidences of temporary and permanent vocal palsy were 5.1% and 0.9%,
      respectively. The rates of temporary/permanent vocal palsy in groups classified
      according to underlying disease were 4.0%/0.2% for benign thyroid disease,
      2.0%/0.7% for thyroid cancer, 12.0%/1.1% for Graves' disease, and 10.8%/8.1% for
      reoperation. Surgery for thyroid cancer, Graves' disease, and recurrent goiter
      were associated with significantly higher vocal palsy rates. Most patients
      without documented nerve damage during the operation recovered from postoperative
      vocal palsy. Total lobectomy with routine RLN identification is recommended as a
      basic procedure in thyroid surgery.

PMID- 15506554
TI  - Comparison of the effect of two different doses of 0.75% glucose-free ropivacaine
      for spinal anesthesia for lower limb and lower abdominal surgery.
AB  - We compared the clinical efficacy and safety of two doses of ropivacaine for
      spinal anesthesia in Chinese patients undergoing lower limb and lower abdominal
      surgery. In this randomized, open-label study, 40 patients were divided into two
      groups: group A received 3.5 mL (26.25 mg) of 0.75% glucose-free ropivacaine, and
      group B received 4.5 mL (33.75 mg). Sensory and motor blocks were assessed during
      and after surgery through to complete recovery. Seven standard measurements were
      taken: time to onset of sensory blocks; maximum sensory cephalad spread; time to
      maximum sensory block; maximum number of blocked segments; duration of sensory
      block at L3; time to onset of complete motor block; and duration until complete
      motor block recovery. Vital signs and any adverse effects related to spinal
      anesthesia were also recorded. No significant differences were found between the
      two groups: time to onset of sensory block at L3 in group A vs B (2.1 +/- 9.6 vs
      1.7 +/- 7.3 minutes), maximum cephalad spread [T4-5 (C3-T11) vs T4 (C3-T8)],
      maximum number of blocked segments (18.0 +/- 3.4 vs 19.8 +/- 3.7), time to
      maximum sensory block (34.0 +/- 22.9 vs 26.8 +/- 17.9 minutes), duration of
      sensory block at L3 (251.2 +/- 34.7 vs 277.3 +/- 51.1 minutes), time to onset of
      complete motor block (13.4 +/- 6.4 vs 10.3 +/- 3.4 minutes), and time for
      complete recovery from motor block (264 +/- 52.1 vs 292.5 +/- 64.5 minutes). No
      significant differences in global hemodynamic changes were found during and after
      the operation. While shivering was more frequent in group B during the operation,
      the difference was not significant. Otherwise, there were no differences in
      adverse effects during and after surgery. We conclude that both doses of 0.75%
      glucose-free ropivacaine, 26.25 mg (3.5 mL) and 33.75 mg (4.5 mL), have the same
      efficacy and safety in Chinese patients undergoing spinal anesthesia for lower
      limb and lower abdominal surgery.

PMID- 15506556
TI  - Differentiation among metastatic brain tumors, radiation necroses, and brain
      abscesses using proton magnetic resonance spectroscopy.
AB  - Magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS)
      were evaluated for differentiating metastatic brain tumors, radiation necroses,
      and brain abscesses. Twelve histologically verified lesions in 12 patients were
      studied using preoperative MRI and proton MRS. The signal intensities of four
      major metabolites, N-acetyl aspartate (NAA), choline-containing compounds (Cho),
      creatine and phosphocreatine (Cr), and lactate (Lac), were observed over the
      region of interest. Metastatic brain tumors showed a decrease in NAA/Cr and an
      increase in Cho/Cr ratios. Radiation necroses showed a decrease in NAA/Cr and no
      change in Cho/Cr ratios. Brain abscesses showed an increase in Lac/Cr ratio.
      Correlation with histopathologic findings showed that a high Cho signal was
      suggestive of a metastatic brain tumor. Lac signals were observed in brain
      abscesses, presumably reflecting the anerobic glycolysis of living cells.
      Although more cases and studies are necessary, metabolic information provided by
      proton MRS combined with MRI is useful for differentiating among metastatic brain
      tumors, radiation necroses, and brain abscesses.

PMID- 15506557
TI  - Comparison of quality of life for people with schizophrenia and mental health of
      caregivers beteen commn-based and hospital-based services.
AB  - This study is a comparison of the quality of life and family stress levels in
      community-based and hospital-based services for people with schizophrenia. Fiscal
      considerations of the health insurance industry in Taiwan require the evaluation
      of a community support program versus the traditional, hospital-centered program
      for reform of mental health policy concerning schizophrenia. The study involved
      52 schizophrenic patients, 27 in a community-based program and 25 in a hospital
      based treatment model, and was conducted from January to December 2001 in the
      psychiatric department of a general teaching hospital in southern Taiwan.
      Outcomes were determined using the World Health Organization quality of life
      questionnaire (WHOQoL-BREF, Taiwan version), Brief Psychiatric Rating Scale
      (BPRS), General Health Questionnaire (Chinese version), rate of loss to follow
      up, job conditions, and social function. Comparisons of quality of life and
      caregiver mental health between the two groups were accomplished using
      descriptive analysis, independent sample t test, and the generalized estimating
      equation-I. No significant differences between the two groups were found in
      quality of life or family mental stress according to the General Health
      Questionnaire after controlling for sex, age, disease duration, full IQ, and
      total BPRS score. Long disease duration predicted a hospital setting, while a
      high IQ was predictive of a community setting. We found no decrease in quality of
      life for schizophrenic patients in a hospital-based program and no increase in
      family mental stress among the community-based group. To improve patients'
      quality of life and the mental health of caregivers in both services, it is
      important to ameliorate severe symptoms associated with schizophrenia.

PMID- 15506558
TI  - A case of subarahnoid hemorrhage with persistent shock and transient ST elevation
      simulating acute myocardial infarction.
AB  - Electrocardiographic changes in neurovascular disease are not rare. Patients with
      subarachnoid hemorrhage have electrocardiographic (ECG) abnormalities that may
      mimic ischemic heart disease and acute myocardial infarction. Outflow of
      catecholamines in the early stage of subarachnoid hemorrhage contributes to
      elevated blood pressure in most patients. Hypotension is a rare presentation in
      subarachnoid hemorrhage. We report a case of subarachnoid hemorrhage with
      transient ST elevation and intractable shock simulating acute myocardial
      infarction, and review the mechanism of ECG changes in subarachnoid hemorrhage.

PMID- 15506559
TI  - Choosing calcium channel blockers for pregnant women with paroxysmal
      supraventriclar tachycardia and preterm labor: a case report.
AB  - Preterm labor is a major clinical hazard causing both maternal and neonatal
      morbidity and mortality. Paroxysmal supraventricular tachycardia (PSVT)
      complicated by preterm labor is rare. Of the many drugs used to treat PSVT, only
      calcium channel blockers are tocolytics. Here, we present the case of a 29-year
      old female admitted to our ward with previously diagnosed PSVT and preterm labor
      at 31 weeks' gestation of her fourth pregnancy. Calcium channel blockers were
      administered and her uterine contractions subsided. Afterwards, no side effects
      were noted and she suffered no further tachycardic attacks during her pregnancy.
      She successfully delivered a full-term baby and received subsequent regular
      follow-up at the outpatient clinic.

PMID- 15506560
TI  - Handlebar hernia with jejunal and duodenal injuries: a case report.
AB  - Traumatic abdominal wall hernia is an uncommon complication of abdominal blunt
      trauma. Handlebar hernia is even more infrequent. To the best of our knowledge,
      there are fewer than 30 cases of handlebar hernia reported in the English
      literature. Associated intra-abdominal injuries are infrequent. We present a case
      of handlebar hernia with jejunal and duodenal injuries. Emergency surgical
      intervention included primary repair of the disrupted musculofascial defect and
      injuries of the duodenum and jejunum. Bile-stained discharge from the drain tube
      was noted, so a second operation was performed about 7 days after the first.
      Leakage from the sutured jejunal perforation and another irregular perforation in
      the posterior wall of the fourth portion of the duodenum were noted. The two
      perforations were debrided and repaired. The muscular and fascial defects were
      debrided and closed with interrupted sutures. The patient recovered smoothly and
      was discharged 30 days after the blunt injury. No other major complication was
      noted 11 months after surgery.

PMID- 15506561
TI  - Total intravenous anesthesia for repair of congenitral diaphragmatic hernia: a
      case report.
AB  - Congenital diaphragmatic hernia is a cardiopulmonary anomaly that causes severe
      respiratory disorder. Traditionally, inhalational anesthetics with mechanical
      hyperventilation, opioids, and muscle relaxants are used in anesthesia for repair
      surgery. In this case, we used total intravenous anesthesia combined with high
      frequency oscillatory ventilation and inhaled nitric oxide for surgical repair of
      the diaphragm. After surgery, the patient recovered well and was discharged from
      hospital 1 month later.

PMID- 15506562
TI  - MCP-1 induces migration of adult neural stem cells.
AB  - As a model for brain inflammation we previously studied transcriptional profiles
      of tumor necrosis factor-alpha (TNF)treated U373 astroglioma cells. In previous
      work we were able to demonstrate that the chemokine monocyte chemoattractant
      protein-1 (MCP-1, SCYA2, CCL2, MCAF) expression in U373 cells was inducible by
      TNF-alpha treatment. Demonstrably MCP-1 mRNA and protein expression in U373 cells
      was sustainable over time and at the highest level of all genes analyzed
      (Schwamborn et al., BMC Genomics 4, 46, 2003). In the hematopoietic system MCP-1
      is a CC chemokine that attracts monocytes, memory T lymphocytes, and natural
      killer cells. In search of further functions in brain inflammation we tested the
      hypothesis that MCP-1 acts as a chemokine on neural stem cells. Here we report
      that MCP-1 activates the migration capacity of rat-derived neural stem cells. The
      migration of stem cells in a Boyden chamber analysis was elevated after
      stimulation with MCP-1. Time-lapse video microscopy visualized the migration of
      single stem cells from neurospheres in MCP-1-treated cultures, whereas untreated
      cultures depicted no migration at all, but showed signs of sprouting. Expression
      of the MCP-1 receptor CCR2 in neurosphere cultures was verified by RT-PCR and
      immunofluorescence microscopy. Supernatants from TNF-treated U373 cells also
      induced migration of neural stem cells.

PMID- 15506563
TI  - Fluoride causes reversible dispersal of Golgi cisternae and matrix in
      neuroendocrine cells.
AB  - A role for heterotrimeric G proteins in the regulation of Golgi function and
      formation of secretory granules is generally accepted. We set out to study the
      effect of activation of heterotrimeric G proteins by aluminum fluoride on
      secretory granule formation in AtT-20 corticotropic tumor cells and in
      melanotrophs from the rat pituitary. In AtT-20 cells, treatment with aluminum
      fluoride or fluoride alone for 60 min induced complete dispersal of Golgi, ER
      Golgi intermediate compartment and Golgi matrix markers, while betaCOP
      immunoreactiviy retained a juxtanuclear position and TGN38 was unaffected.
      Electron microscopy showed compression of Golgi cisternae followed by conversion
      of the Golgi stacks into clusters of tubular and vesicular elements. In the
      melanotroph of the rat pituitary a similar compression of Golgi cisternae was
      observed, followed by a progressive loss of cisternae from the stacks. As shown
      in other cells, brefeldin A induced redistribution of the Golgi matrix protein
      GM130 to punctate structures in the cytoplasm in AtT-20 cells, while mannosidase
      II immunoreactivity was completely dispersed. Fluoride induced a complete
      dispersal of mannosidase II and GM130 immunoreactivity. The effect of fluoride
      was fully reversible with reestablishment of normal mannosidase II and GM130
      immunoreactivity within 2 h. After 1 h of recovery, showing varying stages of
      reassembly, the patterns of mannosidase II and GM130 immunoreactivity were
      identical in individual cells, indicating that Golgi matrix and cisternae
      reassemble with similar kinetics during recovery from fluoride treatment. Instead
      of a specific aluminum fluoride effect on secretory granule formation in the
      trans-Golgi network, we thus observe a unique form of Golgi dispersal induced by
      fluoride alone, possibly via its action as a phosphatase inhibitor.

PMID- 15506564
TI  - The lamina-associated polypeptide 2 (LAP2) genes of zebrafish and chicken: no
      LAP2alpha isoform is synthesised by non-mammalian vertebrates.
AB  - The mammalian lamina-associated polypeptide 2 (LAP2) gene encodes six isoforms
      (LAP2alpha, beta, delta, epsilon, gamma, zeta) that are synthesised from
      alternatively spliced mRNAs. The mammalian LAP2alpha is one of the predominant
      isoforms and localised in the nucleoplasm whereas LAP2beta, delta, epsilon, and
      gamma are integral membrane proteins of the inner nuclear membrane. We have
      analysed the LAP2 gene structure of the zebrafish Danio rerio as an attractive
      lower vertebrate model organism. The zebrafish LAP2 (ZLAP2) gene without
      regulatory sequences spans approximately 19 kb of genomic DNA. It contains 15
      exons that encode the isoforms ZLAP2beta, gamma, and omega which are localised in
      the inner nuclear membrane. By radiation hybrid mapping, we have located the gene
      onto linkage group 4 between EST markers fc01g04 (213.97cR) and fb49f01
      (215.69cR). The identification of a chicken genomic clone comprising the complete
      coding region of the avian LAP2 gene enabled us to compare the LAP2 gene
      structure amongst vertebrates. In contrast to the mammalian LAP2 gene, the
      zebrafish and the chicken sequences do not encode for an alpha-isoform. In
      parallel we searched for an alpha-isoform in birds using polyclonal and
      monoclonal LAP2 antibodies specific for the common evolutionary conserved
      aminoterminal domain present in all isoforms. We detected LAP2beta as the
      predominant isoform but no LAP2alpha in tissues of 10-day-old chicken embryos and
      cultured chicken fibroblasts thus confirming the genomic analysis. The comparison
      of each zebrafish and chicken LAP2 exon with the corresponding exons of the human
      LAP2 gene demonstrates that the degree of identity at the amino acid level is
      much higher between the human and chicken than between the human and zebrafish
      sequences. By Blast search with the nucleotide and amino acid sequences of the
      human LAP2alpha, we did not find any significant homologies in databases of the
      zebrafish and chicken sequences. Our data suggest that LAP2alpha is a novelty of
      mammals.

PMID- 15506565
TI  - Anti-actin antibodies generated against profilin:actin distinguish between non
      filamentous and filamentous actin, and label cultured cells in a dotted pattern.
AB  - Actin polymerization is a prominent feature of migrating cells, where it powers
      the protrusion of the leading edge. Many studies have characterized the well
      ordered and dynamic arrangement of filamentous actin in this submembraneous
      space. However, less is known about the organization of unpolymerized actin.
      Previously, we reported on the use of covalently coupled profilin:actin to study
      actin dynamics and presented evidence that profilin-bound actin is a major source
      of actin for filament growth. To locate profilin:actin in the cell we have now
      used this non-dissociable complex for antibody generation, and obtained
      monospecific anti-actin and anti-profilin antibodies from two separate
      immunizations. Fluorescence microscopy revealed drastic differences in the
      staining pattern generated by the anti-actin antibody preparations. With one,
      distinct puncta appeared at the actin-rich leading edge and sometimes aligned
      with microtubules in the interior of the lamella, while the other displayed
      typical actin filament staining. Labelling experiments in vitro demonstrated
      failure of the first antibody to recognize filamentous actin and none of the two
      bound microtubules. The two anti-profilin antibodies purified in parallel
      generated a punctated pattern similar to that seen with the first anti-actin
      antibody. All antibody preparations labelled the nuclei.

PMID- 15506566
TI  - Differential expression and cellular localization of ERKs during organogenic
      nodule formation from internodes of Humulus lupulus var. Nugget.
AB  - The expression and subcellular localization of extracellular signal-regulated
      kinase 1 or 2 (ERK1/2) homologues (HLERK1/2) during the process of organogenic
      nodule formation in Humulus lupulus var. Nugget was studied using antibodies
      specific for ERK1 and ERK2, and for phosphorylated mitogen-activated protein
      kinases (MAPKs). The increase in HLERK levels, detected by Western blotting 12
      hours after wounding suggests their involvement in response to the wounding
      treatment applied for morphogenesis induction. In dividing cambial cells,
      occurring in between 4 and 7 days after morphogenesis induction, as well as in
      dividing prenodular cells (15 days after induction) HLERK1 and/or 2 were
      localized in the nucleus. However, as soon as nodular cells start proliferating
      to form shoot meristems, HLERK1 and 2 were detected in the cytoplasm and not in
      the nucleus. The data reported account for a differential expression and
      activation of HLERK1 and HLERK2 throughout the process of nodule formation and
      plantlet regeneration. HLERK1 appears to be expressed in the stages of nodule
      formation and plantlet regeneration, playing a possible role in controlling cell
      proliferation and differentiation. HLERK2 may be induced as a response to
      reactive oxygen species (ROS) generated by wounding of internodes as its
      expression is reduced in liquid medium with less oxygen availability compared to
      solid medium. However, addition of a ROS inhibitor to the liquid medium does not
      result in a further decrease in the HLERK2 level.

PMID- 15506567
TI  - Secreted arginases from phylogenetically farrelated lichen species act as cross
      recognition factors for two different algal cells.
AB  - Purified arginases secreted from Evernia prunastri and Xanthoria parietina thalli
      hydrolyze arginine in a Mn2+ -dependent reaction. Ca2+ cannot replace Mn2+, but
      its addition to reaction mixtures in the presence of Mn2+ significantly inhibited
      arginase activity. Arginases from both lichen species also show lectin function,
      binding to the cell wall of both homologous and heterologous algae. Such binding
      is enhanced by both Ca2+ and Mn2+ and results in cytoagglutination, which is
      counteracted by alpha-D-galactose. A putative ligand for these lectins consists
      of a glycosylated urease, the polysaccharide moiety of which is uniquely composed
      of alpha-D-galactose. Binding of lectins inhibits its enzymatic activity, which
      is recovered after desorption of the lectin with alpha-D-galactose. Urease is
      also eluted from arginase-agarose columns by using alpha-D-galactose as eluent.
      Data demonstrate ligand-dependent retention of the fungal lectin on the algal
      cell surface and this is consistent with a model of recognition of compatible
      algae, through which algal cells would form a lichen with a lectin-secreting
      fungus only when these cells contain the specific ligand for the lectin in their
      cell walls. This is, lectin binding is used as a mechanism for ensuring
      specificity in the association.

PMID- 15506568
TI  - Continuity, care, and commitment: the course of patient-clinician relationships.

PMID- 15506569
TI  - Prevalence and predictors of night sweats, day sweats, and hot flashes in older
      primary care patients: an OKPRN study.
AB  - PURPOSE: We wanted to estimate the prevalence of night sweats, day sweats, and
      hot flashes in older primary care patients and identify associated factors.
      METHODS: We undertook a cross-sectional study of patients older than 64 years
      recruited from the practices of 23 family physicians. Variables included
      sociodemographic information, health habits, chronic medical problems, symptoms,
      quality of life, and the degree to which patients were bothered by night sweats,
      daytime sweating, and hot flashes. RESULTS: Among the 795 patients, 10% reported
      being bothered by night sweats, 9% by day sweats, and 8% by hot flashes. Eighteen
      percent reported at least 1 of these symptoms. The 3 symptoms were strongly
      correlated. Factors associated with night sweats in the multivariate models were
      age (odds ratio [OR] 0.94/y; 95% confidence interval [CI], 0.89-0.98), fever (OR
      12.60; 95% CI, 6.58-24.14), muscle cramps (OR 2.84; 95% CI, 1.53-5.24), numbness
      of hands and feet (OR 3.34; 95% CI, 1.92-5.81), impaired vision (OR 2.45; 95% CI,
      1.41-4.27), and hearing loss (OR 1.84; 95% CI, 1.03-3.27). Day sweats were
      associated with fever (OR 4.10; 95% CI, 2.14-7.87), restless legs (OR 3.22; 95%
      CI, 1.76-5.89), lightheadedness (OR 2.24; 95% CI, 1.30-3.88), and diabetes (OR
      2.19; 95% CI, 1.22-3.92). Hot flashes were associated with nonwhite race (OR
      3.10; 95% CI, 1.60-5.98), fever (OR 3.98; 95% CI, 1.97-8.04), bone pain (OR 2.31;
      CI 95%: 1.30-4.08), impaired vision (OR 2.12; 95% CI, 1.19-3.79), and nervous
      spells (OR 1.87; 95% CI, 1.01-3.46). All 3 symptoms were associated with reduced
      quality of life. CONCLUSION: Many older patients are bothered by night sweats,
      day sweats, and hot flashes. Though these symptoms are similar and related, they
      have somewhat different associations with other variables. Clinical evaluation
      should include questions about febrile illnesses, sensory deficits, anxiety,
      depression, pain, muscle cramps, and restless legs syndrome.

PMID- 15506570
TI  - Comfortably engaging: which approach to alcohol screening should we use?
AB  - PURPOSE: We wanted to compare 2 screening instruments for problem drinking, the
      CAGE and a single question, assessing frequency of use, patient and clinician
      comfort, and patient engagement in change. METHODS: The study was a crossover,
      cluster-randomized clinical trial with 31 clinicians in Missouri and 13 in the
      American Academy of Family Physicians (AAFP) National Network for Family Practice
      and Primary Care Research; 2,800 patients provided data. The clinician was the
      unit of randomization. Clinicians decided whether to screen each patient; if they
      chose to screen, they used the screening approach assigned for that block of
      patients. The clinician and patient separately completed questionnaires
      immediately after the office visit to assess each one's comfort with screening
      (and any ensuing discussion) and the patient's engagement in change. RESULTS:
      Missouri clinicians screened more patients when assigned the single question
      (81%) than the CAGE (69%, P = .001 in weighted analysis). There was no difference
      among AAFP network clinicians (96% of patients screened with the CAGE, 97% with
      the single question). Eighty percent to 90% of clinicians and 70% of patients
      reported being comfortable with screening and the ensuing discussion, with no
      difference between approaches in either network. About one third of patients who
      were identified as problem drinkers reported thinking about or planning to change
      their drinking behavior, with no difference in engagement between screening
      approaches. CONCLUSIONS: Clinicians and patients reported similar comfort with
      the CAGE questions and the single-question screening tools for problem drinking,
      and the 2 instruments were equal in their ability to engage the patient. In
      Missouri, the single question was more likely to be used.

PMID- 15506571
TI  - How many problems do family physicians manage at each encounter? A WReN study.
AB  - PURPOSE: The number of problems managed concurrently by family physicians during
      patient encounters has not been fully explored despite the implications for
      quality assessment, guideline implementation, education, research,
      administration, and funding. Our study objective was to determine the number of
      problems physicians report managing at each visit and compare that with the
      number reflected in the chart and the bill. METHODS: Twenty-nine members of the
      Wisconsin Research Network reported on encounters with 572 patients using a
      physician problem log. The patient chart notes and the diagnoses submitted for
      billing from the encounters were compared with the information in these logs.
      RESULTS: The physicians reported managing an average of 3.05 problems per
      encounter and recorded 2.82 in the chart and 1.97 on the bill. For all patients,
      37% of encounters addressed more than 3 problems, and 18% addressed more than 4.
      For patients older than 65 years, there was an average of 3.88 problems at each
      visit, and for diabetic patients there was an average of 4.60. There was evidence
      for the selective omission of mental health and substance problems from the
      diagnoses used for billing. CONCLUSIONS: Family medicine involves the concurrent
      care of multiple problems, which billing data do not adequately reflect. Our
      findings suggest a mismatch between family medicine and current approaches to
      quality assessment, guideline implementation, education, research,
      administration, and funding. Activities in all these areas need to address the
      physician's task of prioritizing and integrating care for multiple problems
      concurrently.

PMID- 15506572
TI  - Seasonal variation in diagnoses and visits to family physicians.
AB  - BACKGROUND: Practice-based research networks (PBRNs) replicating the National
      Ambulatory Medical Care Survey (NAMCS) must sample more than 1 year to account
      for presumed seasonal variation in illnesses. This study evaluated the effects of
      seasonality on diagnoses within NAMCS family physician data. METHODS: Using
      combined data from the 1995-1998 NAMCS, diagnostic clusters that accounted for
      more than 1% of total visits were analyzed for seasonality. Seasons were coded
      categorically as dummy variables with summer as the reference category. A
      logistic regression was performed with each diagnosis as an outcome on the full
      data. To examine the ability of alternative sampling strategies to replicate the
      full year of data, a simulation study was carried out drawing 50 samples of 1,000
      visits each for winter-summer and spring-fall sampling periods. RESULTS: We found
      23 diagnostic clusters that had a frequency more than 1%, of which 10 had
      seasonal variations (P < or = .001), primarily between winter and summer. If
      sampling were restricted to spring, the diagnostic clusters of pregnancy and
      coronary artery disease would account for less than 1% of visits. All other
      diagnostic clusters, though changing rank order, would account for more than 1%
      if sampled in a single quarter. In the simulated sampling strategy, visit
      prevalence dropped below 1% for at least 1 diagnosis in 24 of 50 samples in
      spring-fall compared with 20 of 50 samples for winter-summer (P > .20).
      CONCLUSIONS: There is little seasonal variation in the 23 diagnoses that occur in
      more than 1% of visits to family physicians. There is, however, important
      seasonal variation in the rank order of these diagnoses. A sampling strategy that
      uses any quarter of the year but spring (March, April, May) could be used to
      understand what diagnoses are frequently seen within a PBRN.

PMID- 15506573
TI  - Evaluating computer capabilities in a primary care practice-based research
      network.
AB  - PURPOSE: We wanted to assess computer capabilities in a primary care practice
      based research network and to understand how receptive the practices were to new
      ideas for automation of practice activities and research. METHOD: This study was
      conducted among members of the Pediatric Practice Research Group (PPRG). A survey
      to assess computer capabilities was developed to explore hardware types, software
      programs, Internet connectivity and data transmission; views on privacy and
      security; and receptivity to future electronic data collection approaches.
      RESULTS: Of the 40 PPRG practices participating in the study during the autumn of
      2001, all used IBM-compatible systems. Of these, 45% used stand-alone desktops,
      40% had networked desktops, and approximately 15% used laptops and minicomputers.
      A variety of software packages were used, with most practices (82%) having
      software for some aspect of patient care documentation, patient accounting (90%),
      business support (60%), and management reports and analysis (97%). The main
      obstacles to expanding use of computers in patient care were insufficient staff
      training (63%) and privacy concerns (82%). If provided with training and support,
      most practices indicated they were willing to consider an array of electronic
      data collection options for practice-based research activities. CONCLUSIONS:
      There is wide variability in hardware and software use in the pediatric practice
      setting. Implementing electronic data collection in the PPRG would require a
      substantial start-up effort and ongoing training and support at the practice
      site.

PMID- 15506574
TI  - Exploring patient reactions to pen-tablet computers: a report from CaReNet.
AB  - PURPOSE: We wanted to study patient receptivity to using pen-tablet computers for
      collecting data in a practice-based research network. METHODS: We analyzed exit
      interviews and field notes collected by trained research assistants as part of a
      larger Colorado Research Network (CaReNet) study comparing pen-tablet and paper
      pencil methods to collect data for the Primary Care Network Survey (PRINS).
      RESULTS: A total of 168 patients completed a patient exit interview after
      completion of the pen-tablet-based survey instrument. Analyses of these brief
      interviews and field notes indicated that patients had favorable reactions to
      using pen-tablet computers. The most common barriers were related to glitches in
      the technology; the voice recognition software was the most problematic, with
      patients (as well as clinicians) finding this feature to be frustrating.
      CONCLUSIONS: Patients were able and willing to use pen-tablet computers for
      completing forms within busy primary care offices. Increasing patient involvement
      in practice-based research may be even more practicable through the use of this
      novel technology, which can allow patient-directed data collection at a single
      point in time as well as longitudinally.

PMID- 15506575
TI  - How and why to study the practice content of a practice-based research network.
AB  - BACKGROUND: We describe the rationale, methods, and important lessons learned
      from doing a practice content study in a new practice-based research network
      (PBRN). METHODS: We performed a modified replication of the National Ambulatory
      Medical Care Survey (NAMCS) in the Kentucky Ambulatory Network (KAN). Network
      clinicians had input into focused modifications of the NAMCS protocol, including
      addition of data fields of special interest to them. Cross-sectional sampling of
      patient visits was done for a 1-year period, with each practice collecting data
      during 2 separate weeks. We used selected results to illustrate lessons learned
      and the value of this endeavor. RESULTS: Twenty-three KAN clinicians helped
      recruit 33 of their colleagues, and these 56 community-based primary care
      clinicians collected data on 2,228 office visits. Patient demographics (except
      race) and the top 10 diagnoses were similar to US NAMCS data. One third of visits
      addressed 3 or more diagnoses, and one fourth of the visits involved 4 or more
      medications. The top 10 primary diagnoses represented only one third of all
      primary diagnoses. Seventy percent of adult patients were either overweight (30%)
      or obese (40%). Rates of counseling on diet or exercise rose with increases in
      body mass index. CONCLUSION: This study helped us establish and activate our new
      PBRN, increasing its membership in the process. The descriptive data gained will
      stimulate, guide, and support our future research activities.

PMID- 15506576
TI  - Opportunities, challenges, and lessons of international research in practice
      based research networks: the case of an international study of acute otitis
      media.
AB  - The requirements of research become more complex and demanding in international
      collaborations. The opportunity to study naturally occurring variation in
      treatment prompted networking primary care research networks in the United
      Kingdom, The Netherlands, and North America to study acute otitis media.
      Additional challenges faced and addressed in this study included (1) differing
      national requirements for protecting human subjects; (2) variation in data
      collection processes in primary care practices; (3) data transmission among
      participants; (4) duties and tariffs on necessary instruments; (5) fluctuation in
      currency exchange rates; (6) incapacitation of coinvestigators; (7) complex
      administration of funds; (8) financing the additional, legitimate costs of
      collaboration; (9) sustaining strong personal relationships among
      coinvestigators; and (10) accepting longer time frames than would otherwise be
      expected. Overall, international practice-based research can be productive,
      affect millions of people, and be extremely rewarding to investigators. It is
      not, however, for the faint-hearted.

PMID- 15506577
TI  - Rapid assessment of agents of biological terrorism: defining the differential
      diagnosis of inhalational anthrax using electronic communication in a practice
      based research network.
AB  - PURPOSE: Early detection of bioterrorism requires assessment of diagnoses
      assigned to cases of rare diseases with which clinicians have little experience.
      In this study, we evaluated the process of defining the differential diagnosis
      for inhalational anthrax using electronic communication within a practice-based
      research network (PBRN) and compared the results with those obtained from a
      nationwide random sample of family physicians with a mailed instrument. METHODS:
      We distributed survey instruments by e-mail to 55 physician members of the
      Wisconsin Research Network (WReN), a regional PBRN. The instruments consisted of
      3 case vignettes randomly drawn from a set describing 11 patients with
      inhalational anthrax, 2 with influenza A, and 1 with Legionella pneumonia.
      Physicians provided their most likely nonanthrax diagnosis, along with their
      responses to 4 yes-or-no management questions for each case. Physicians who had
      not responded at 1 week received a second e-mail with the survey instrument. The
      comparison group consisted of the nationwide sample of physicians who completed
      mailed survey instruments. Primary outcome measures were response rate, median
      response time, and frequencies of diagnostic categories assigned to cases of
      inhalational anthrax. RESULTS: The PBRN response rate compared favorably with
      that of the national sample (47.3% vs 37.0%; P = not significant). The median
      response time for the PBRN was significantly shorter than that for the national
      sample (2 vs 28 days; P < .001). No significant differences were found between
      the PBRN and the Midwest subset of the national sample in the frequencies of
      major diagnostic categories or in case management. CONCLUSIONS: Electronic means
      of creating differential diagnoses for rare infectious diseases of national
      significance is feasible within PBRNs. Information is much more rapidly acquired
      and is consistent with that obtained by conventional methods.

PMID- 15506578
TI  - The primary care differential diagnosis of inhalational anthrax.
AB  - PURPOSE: Inhalational anthrax is an extremely rare infectious disease with
      nonspecific initial symptoms, thus making diagnosis on clinical grounds
      difficult. After a covert release of anthrax spores, primary care physicians will
      be among the first to evaluate cases. This study defines the primary care
      differential diagnosis of inhalational anthrax. METHODS: In May 2002, we mailed
      survey instruments consisting of 3 randomly chosen case vignettes describing
      patients with inhalational anthrax to a nationwide random sample of 665 family
      physicians. Nonrespondents received additional mailings. Physicians were asked to
      provide their most likely nonanthrax diagnosis for each case. RESULTS: The
      response rate was 36.9%. Diagnoses for inhalational anthrax were grouped into 35
      diagnostic categories, with pneumonia (42%), influenza (10%), viral syndrome
      (9%), septicemia (8%), bronchitis (7%), central nervous system infection (6%),
      and gastroenteritis (4%) accounting for 86% of all diagnoses. Diagnoses differed
      significantly between cases that proved to be fatal and those that proved to be
      nonfatal. CONCLUSIONS: Inhalational anthrax resembles common diagnoses in primary
      care. Surveillance systems for early detection of bioterrorism events that rely
      only on diagnostic codes will be hampered by false-positive alerts. Consequently,
      educating frontline physicians to recognize and respond to bioterrorism is of the
      highest priority.

PMID- 15506579
TI  - Interpersonal continuity of care and patient satisfaction: a critical review.
AB  - PURPOSE: We wanted to review the medical literature regarding the relationship
      between interpersonal continuity of care and patient satisfaction and suggest
      future strategies for research on this topic. METHODS: A search of the MEDLINE
      database from 1966 through April 2002 was conducted to find articles focusing on
      interpersonal continuity of patient care. The resulting articles were screened to
      select those focusing on the relationship between interpersonal continuity in the
      doctor-patient relationship and patient satisfaction. These articles were
      systematically reviewed and analyzed for study method, measurement technique, and
      the quality of evidence. RESULTS: Thirty articles were found that addressed the
      relationship between interpersonal continuity and patient satisfaction with
      medical care. Twenty-two of these articles were reports of original research.
      Nineteen of the 22, including 4 clinical trials, reported significantly higher
      satisfaction when interpersonal continuity was present. CONCLUSIONS: Although the
      available literature reflects persistent methodologic problems, a consistent and
      significant positive relationship exists between interpersonal continuity of care
      and patient satisfaction. Future research in this area should address whether the
      same is true for all patients or only for those who seek ongoing relationships
      with physicians in primary care.

PMID- 15506580
TI  - Patient-physician shared experiences and value patients place on continuity of
      care.
AB  - PURPOSE: We undertook a study to examine the impact of experiences shared between
      patient and physician and the value patients place on continuity of care.
      METHODS: Data on 4,454 patients collected in The Direct Observation of Primary
      Care (DOPC) study conducted between October 1994 and August 1995 were analyzed to
      assess the value patients place on continuity, length of patient-physician
      relationship, and experiences shared between patient and physician. RESULTS: A
      significant interaction was yielded between duration of relationship and
      experiences shared between patient and physician (P = .03). For all lengths of
      relationship with the physician, the value that patients have for continuity
      increased when patients indicated experiences shared with the physician. For
      patients who did not report experiences shared with the physician, the longer the
      relationship, the greater the value placed on continuity. CONCLUSIONS: The
      results of this study point to the importance of the experiences shared between
      patients and physicians and the value that patients place on continuity with
      their regular physician.

PMID- 15506581
TI  - Physician-patient relationship and medication compliance: a primary care
      investigation.
AB  - PURPOSE: We assessed the relationship between 4 attributes of the physician
      patient relationship and medication compliance. METHODS: We conducted a waiting
      room survey of patients consulting 22 general practitioners in 14 randomly
      selected practices in Auckland, New Zealand (81% response rate). A total of 370
      consecutive patients (75% response rate) completed survey instruments about 4
      attributes of the physician-patient relationship. Continuity of care (assessed
      from use of a usual physician, length of continuity, and perceived importance of
      continuity) and trust in the physician were ascertained before the consultation.
      After the consultation the Patient Enablement Index measured the physician's
      ability to enable patients in self-care, and concordance between the patient and
      physician was measured by a 6-item inventory of perceived agreement about the
      presenting problem and management, were ascertained immediately after the
      consultation. Compliance with prescribed medication therapy was ascertained by
      telephone follow-up 4 days after the consultation. RESULTS: Overall, 220 patients
      (61%) received a prescription, and 79% of these patients were taking the
      medication at follow-up. In a univariate analysis adjusted for clustering, only
      trust and physician-patient concordance were significantly related to compliance.
      In analysis further adjusted for health and demographic factors, physician
      patient concordance was independently related to compliance (odds ratio = 1.34,
      95% confidence interval, 1.04-1.72). CONCLUSIONS: Primary care consultations with
      higher levels of patient-reported physician-patient concordance were associated
      with one-third greater medication compliance. An emphasis on understanding and
      facilitating agreement between physician and patient may benefit outcomes in
      primary care.

PMID- 15506582
TI  - Patients' needs for contact with their GP at the time of hospital admission and
      other life events: a quantitative and qualitative exploration.
AB  - PURPOSE: Our goal was to explore patients' anticipated needs for contact with
      their general practitioner (GP) at the time of hospital admissions and other life
      events. METHODS: We undertook a questionnaire survey of 875 patients from 35
      general practices spread throughout The Netherlands and a qualitative interview
      study with 30 patients. RESULTS: Most patients expected to need contact with
      their GP if admitted to a hospital for a serious condition, such as a malignancy
      (98%) or a heart attack (97%). For minor conditions, such as a minor foot
      operation, contact was considered less important (33%). At the time of major life
      events, many patients anticipated needing contact as well: 81% in the case of a
      birth within the family, 90% in the case of a death in the family. In the
      quantitative analysis patients' wants were related only to a minor extent to
      patient characteristics. The qualitative analysis, however, distinguished
      categories of patients with different needs. Some patients were more technical in
      their needs, others focussed primarily on the relationship. CONCLUSION: Patients
      appear to have considerable need for contact with their physician at the time of
      hospital admission and other life events. The profession should reflect on this
      underexplored field and attempt to take a policy-making position toward
      initiating patient contact.

PMID- 15506583
TI  - Should years of schooling be used to guide treatment of coronary risk factors?
AB  - PURPOSE: We wanted to compare the risk of death from coronary heart disease (CHD)
      for patients of low socioeconomic status, measured by educational level, with
      established risk factors. METHODS: We undertook a prospective cohort study.
      Participants included a representative sample of 6,479 adults aged 25 to 74 years
      in the United States who were free of CHD at enrollment in the first National
      Health and Nutrition Examination Survey (NHANES I). RESULTS: Baseline measures
      included years of education, age, sex, systolic blood pressure, diabetes, total
      cholesterol level, and smoking. Outcome was death within 10 years from CHD. The
      relative risk (RR) associated with less than 12 years of education compared with
      more than 12 years (RR 1.5; 95% confidence interval [CI], 1.2-1.8) was comparable
      to being male (RR 1.4; 95% CI, 1.2-1.6), smoking (RR 1.4; 95% CI, 1.1-1.6),
      having a total cholesterol level of greater than 280 mg/dL (RR 1.6; 95% CI, 0.9
      2.7), and systolic blood pressure of 130-139 mm Hg (RR 1.6; 95% CI, 1.0-2.4).
      Findings were comparable for estimates of absolute risk. CONCLUSIONS: Low
      educational level is associated with comparable risk as established risk factors
      for CHD mortality. Incorporation of educational level into risk-based guidelines
      for treatment could potentially reduce socioeconomic disparities in CHD by
      lowering thresholds for treatment.

PMID- 15506584
TI  - Brief physician advice for high-risk drinking among young adults.
AB  - BACKGROUND: High-risk alcohol use in persons 18 to 30 years of age is a critical
      public health problem. It is the number 1 cause of death in this population. This
      article reports the results of a subanalysis of young adults (aged 18 to 30
      years) who participated in Project TrEAT (Trial of Early Alcohol Treatment)
      conducted in the offices of 64 primary care physicians located in 10 counties in
      southern Wisconsin. METHODS: Project TrEAT was a randomized clinical trial
      designed to test the efficacy of a brief intervention protocol to reduce alcohol
      use, improve health status, and decrease health care utilization. A total of 226
      young adults were randomly assigned to either a usual care or brief intervention
      group. RESULTS: There were no significant differences between the 2 groups at
      baseline on a number of potential confounders. During the 4-year follow-up
      period, there were significant reductions in number of persons drinking more than
      3 drinks per day, average 7-day alcohol use, number of persons drinking 6 or more
      drinks per occasion, and number of binge drinking episodes in the previous 30
      days (P < .01 to P < .001). There were also significant differences (P < .05) in
      emergency department visits (103 vs 177), motor vehicle crashes (9 vs 20), total
      motor vehicle events (114 vs 149), and arrests for controlled substance or liquor
      violation (0 vs 8). CONCLUSION: In this 4-year subanalysis of young adults who
      participated in Project TrEAT, we found long-term reductions in high-risk
      drinking behaviors and consequences. The findings of this study support more
      widespread implementation of brief interventions in primary care settings.

PMID- 15506585
TI  - Age-related disparities in cancer screening: analysis of 2001 Behavioral Risk
      Factor Surveillance System data.
AB  - PURPOSE: Although few studies have explored age-related health care disparities,
      some researchers have asserted such disparities uniformly disfavor the elderly
      and are largely attributable to ageism in the health care system. We compared age
      related patterns of screening for colorectal cancer with those for breast and
      prostate cancer in persons aged 50 years and older. METHODS: We analyzed data for
      all adults aged 50 years and older (N = 88,213) in the 2001 Behavioral Risk
      Factor Surveillance System (BRFSS), a nationally representative, telephone
      administered survey of personal health behaviors. Main outcome measures were
      adjusted prevalence by 5-year age-groups of colorectal cancer screening using
      fecal occult blood testing, flexible sigmoidoscopy, or colonoscopy for men and
      women; rates of mammography screening for women; and rates of prostate-specific
      antigen (PSA) screening for men. RESULTS: After adjustment for race/ethnicity,
      education level, income, health insurance, and self-rated health, predicted
      reported colorectal cancer screening (all modalities) increased significantly
      from when patients reached age 50 years until 70 to 74 years (66.0%, standard
      error [SE] 0.8%), remained constant until age 80 years, and then declined. The
      age-related gain in colorectal cancer screening was confined to whites among
      patients older than 60 years. Reported PSA screening increased until age 75 to 79
      years (79.3%, SE 1.1%) and then declined, whereas reported mammography screening
      peaked at age 55 to 59 years (83.3%, SE 1.2%) and then declined. CONCLUSIONS:
      Significant age-related disparities appear to exist for both evidence-based and
      non-evidence-based cancer-screening interventions. The issue of age-related
      disparities in cancer screening is complex, with the direction of disparity
      favoring the elderly for some services yet disfavoring them for others.

PMID- 15506586
TI  - Changing prescribing patterns and increasing prescription expenditures in
      Medicaid.
AB  - PURPOSE: Prescription drug expenditures are the most rapidly growing component of
      total health care expenditures and particularly affect state Medicaid programs.
      We determined the extent to which increasing prescription price and changing
      prescribing patterns contribute to rising prescription expenditures in Medicaid.
      METHODS: We conducted a claims-based analysis comparing annual prescription drug
      expenditures and prescribing patterns. Prescription drug and outpatient visit
      claims for all North Carolina Medicaid enrollees from 1998 through 2000 were
      included. We analyzed drugs individually by combining all prescriptions and
      expenditures for the same drug formulation, and we calculated the number of units
      dispensed per person-year of enrollment. RESULTS: Prescription drug coverage for
      1 person-year cost 503 dollars in 1998 and 759 dollars in 2000, for an annual
      increase of 22.8%. The average number of prescriptions filled per person-year
      increased from 13.0 in 1998 to 15.5 in 2000. Increased prescribing for 6 drugs
      accounted for more than 25% of the total increase in expenditures. The price for
      the 15 most expensive drugs increased an average of 4.1% annually. CONCLUSIONS:
      Prices for existing drugs increased slightly during the study period, but the
      major cause of the increase in drug costs was an increase in the number of
      prescriptions for new and more expensive medications. Prescribing patterns in
      Medicaid differ somewhat from those in the private sector and partly reflect the
      population with low socioeconomic status and high health care needs that it
      serves. To help control rising prescription drug expenditures, efforts should be
      undertaken to improve appropriate and cost-effective prescribing.

PMID- 15506587
TI  - Impact of an evidence-based computerized decision support system on primary care
      prescription costs.
AB  - PURPOSE: Although newer, heavily promoted medications are commonly prescribed,
      published evidence and consensus guidelines often support the use of less
      expensive alternatives. This study was designed to evaluate the impact on
      prescription costs of a computerized decision support system (CDSS) that provides
      evidence-based recommendations to clinicians during the electronic prescribing
      process. METHODS: A retrospective cohort study was performed using a pharmacy
      claims database. Clinicians using the CDSS were matched with a control group by
      pharmacy billed amount, number of patients treated, and number of new
      prescriptions filled during a 6-month baseline period in which neither group used
      the system. The primary outcome measure was the difference in prescription costs
      between the 2 groups after implementation of the CDSS in the intervention group.
      RESULTS: Clinicians who received evidence-based messages had significantly lower
      prescription costs than those in the control group. The average cost per new
      prescription was 4.16 dollars lower (P = .02) in the intervention group, and the
      average cost for new and refilled prescriptions was 4.99 dollars lower (P = .01).
      The 6-month savings from new prescriptions and their refills are estimated to be
      3,450 dollars (95% CI, 1,030-5,863 dollars) per clinician. CONCLUSIONS: Providing
      electronic, evidence-based decision support during the prescribing process can
      shift prescribing decisions toward more evidence-based care and significantly
      decrease primary care prescription costs.

PMID- 15506588
TI  - The Spirituality Index of Well-Being: a new instrument for health-related quality
      of-life research.
AB  - PURPOSE: Despite considerable interest in examining spirituality in health
      related quality-of-life studies, there is a paucity of instruments that measure
      this construct. The objective of this study was to test a valid and reliable
      measure of spirituality that would be useful in patient populations. METHODS: We
      conducted a multisite, cross-sectional survey using systematic sampling of adult
      outpatients at primary care clinic sites in the Kansas City metropolitan area (N
      = 523). We determined the instrument reliability (Cronbach's alpha, test-retest)
      and validity (confirmatory factor analysis, convergent and discriminant
      validation) of the Spirituality Index of Well-Being (SIWB). RESULTS: The SIWB
      contains 12 items: 6 from a self-efficacy domain and 6 from a life scheme domain.
      Confirmatory factor analysis found the following fit indices: chi2 (54, n = 508)
      = 508.35, P < .001; Comparative Fit Index = .98; Tucker-Lewis Index = .97; root
      mean square error of approximation = .13. The index had the following reliability
      results: for the self-efficacy subscale, alpha = .86 and test-retest r = 0.77;
      for the life scheme subscale, alpha = .89 and test-retest r = 0.86; and for the
      total scale alpha = .91 and test-retest r = 0.79, showing very good reliability.
      The SIWB had significant and expected correlations with other quality-of-life
      instruments that measure well-being or spirituality: Zung Depression Scale (r = 0
      .42, P < .001), General Well-Being Scale (r = 0.64, P < .001), and Spiritual Well
      Being Scale (SWB) (r = 0.62, P < .001). There was a modest correlation between
      the religious well-being subscale of the SWB and the SIWB (r = 0.35, P < .001).
      CONCLUSIONS: The Spirituality Index of Well-Being is a valid and reliable
      instrument that can be used in health-related quality-of-life studies.

PMID- 15506589
TI  - Adapting psychosocial intervention research to urban primary care environments: a
      case example.
AB  - PURPOSE: We wanted to describe the unique issues encountered by our research team
      in testing an intervention to reduce perinatal depression in real-world community
      health centers. METHOD: We used a case study of an experience in conducting a
      randomized controlled trial designed to test the effectiveness of a low-cost
      multimodal psychosocial intervention to reduce prenatal and postpartum
      depression. Low-income minority women (N = 187) with low-risk pregnancies were
      randomly assigned to the intervention or treatment as usual. Outcomes of interest
      were depressive symptoms and social support assessed at 3 months' postpartum.
      RESULTS: Our intervention was not associated with changes in depressive symptoms
      or social support. Challenges in implementation were related to participant
      retention and intervention delivery. Turnover of student therapists affected
      continuity in participant-therapist relationships and created missed
      opportunities to deliver the intervention. The academic-community partnership
      that was formed also required more involvement of health center personnel to
      facilitate ownership at the site level, especially for fidelity monitoring. While
      attentive to cultural sensitivity, the project called for more collaboration with
      participants to define common goals and outcomes. Participatory research
      strategies could have anticipated barriers to uptake of the intervention and
      achieved a better match between outcomes desired by researchers and those of
      participants. CONCLUSION: Several criteria for future research planning emerged:
      assessing what the population is willing and able to accept, considering what
      treatment providers can be expected to implement, assessing the setting's
      capacity to accommodate intervention research, and collecting and using emerging
      unanticipated data.

PMID- 15506591
TI  - Linking Ruth to her past.
AB  - A family physician shares the story of her 3-decade-long relationship with a
      patient and the strong ties that they formed. Although she was taught to keep
      emotionally distant from her patients in order to maintain the best therapeutic
      milieu, this relationship enriched the author's experience as a physician and
      ministered to her patient's needs.

PMID- 15506590
TI  - Towards a new understanding of provider continuity.
AB  - Provider continuity is in need of an expanded definition that is not exclusively
      clinician centered. Currently, provider continuity is defined by visits over time
      to the same clinician. Many patients and informal caregivers, however, are co
      providers of health care, not merely consumers. As a result, provider continuity
      will not happen if there is a lack of consistency in who attends with or for the
      patient during successive visits. Such fragmentation may weaken knowledge of the
      patient and information exchange. Consequently, there is a need to redefine
      provider continuity to mean that the same attendees visit the same clinician(s),
      service, or facility as an uninterrupted succession of events. More than semantic
      quibbling, the proposed reconceptualization challenges the foundation of family
      medicine in terms of the values and language by which the discipline defines
      itself in clinician-centered ways. The change required has implications for
      practice and research.

PMID- 15506592
TI  - Obesity and departments of family medicine.

PMID- 15506593
TI  - Promoting scholarly activity in family medicine residency programs: what's the
      reward?

PMID- 15506594
TI  - Networks for new knowledge in family medicine.

PMID- 15506595
TI  - Family doctors demonstrate benefits when new model of care becomes reality.

PMID- 15506596
TI  - Comparison after 10 years of two 100-patient cohorts operated on for
      eviscerations or enucleations.
AB  - PURPOSE: To compare the indications, surgical techniques, and operative outcome
      between two 100-patient populations operated on for evisceration or enucleation
      with a 10-year interval. METHODS: This retrospective study involved 100 patients
      operated on between 1987 and 1990 (Group 1) compared with another 100 patients
      operated on between 1996 and 2000 (Group 2). Group 1 included 64 males and 36
      females, mean age 49 years; Group 2 included 60 males and 40 females, mean age
      53. RESULTS: In Group 1, 19 eviscerations were performed, versus 55 in Group 2.
      In both groups, half of the indications for surgery were a painful blind eye. In
      Group 1, endophthalmia (23%) came second, whereas it was trauma (15%) in Group 2.
      Sixty-eight patients were implanted in Group 1 (silicone spheres 69%) versus 86
      in Group 2 (hydroxyapatite spheres 69%). Twenty spheres (20%) were rejected in
      Group 1 versus 7% in Group 2. DISCUSSION AND CONCLUSIONS: The proportion of
      eviscerations increased in 10 years. The number of endophthalmitis-related
      operations decreased and trauma-related operations increased. The number of
      implantations increased with hydroxyapatite as the first choice material instead
      of silicone. This most likely contributed to reducing the number of rejections.

PMID- 15506597
TI  - Impact of preoperative testing on ophthalmologic and systemic outcomes in
      cataract surgery.
AB  - PURPOSE: To evaluate the incidence of ophthalmologic and systemic complications
      in patients who undergo cataract surgery without preoperative tests compared to
      subjects undergoing cataract surgery preceded by preoperative tests. METHODS: The
      randomized controlled study included 1276 consecutive patients admitted to the
      Institute of Ophthalmology of the University of Modena and Reggio Emilia for
      cataract surgery. The patients were randomly divided into two groups: 638 were
      assigned not to undergo preoperative evaluation based on routine medical tests
      and electrocardiograms; the other 638 underwent preoperative evaluation based on
      said tests. Ophthalmologic and systemic complications were assessed
      intraoperatively and 1 month after surgery. RESULTS: Eleven intraoperative
      complications occurred in the group without preoperative tests and eight in the
      group with preoperative tests; at 1 month six complications were recorded in the
      group without tests and five in the group with tests. Systemic adverse events
      occurred intraoperatively in four patients, whereas no systemic adverse event was
      recorded at 1 month in either group. No statistically significant differences
      were observed between the two groups. CONCLUSIONS: The findings of this study
      have broad applicability, because the sample is representative of the population
      existing in numerous social and healthcare settings; they are of value for
      administrative purposes, because they may be taken as reference in resource
      allocation plans; and they have medicolegal implications, as the resulting
      conduct of healthcare providers is supported by a rigorous scientific study.

PMID- 15506598
TI  - The effects of three-piece or single-piece acrylic intraocular lens implantation
      on posterior capsule opacification.
AB  - PURPOSE: To evaluate the development of posterior capsule opacification (PCO) in
      patients implanted with 5.5 mm optics, single-piece or three-piece acrylic
      intraocular lens (IOL) in cataract surgery prospectively. METHODS: This study was
      carried out on 267 eyes of 249 patients implanted with three-piece, 5.5 mm
      optics, acrylic IOL and 252 eyes of 244 patients implanted with single-piece, 5.5
      mm optics, acrylic IOL by phacoemulsification technique between September 2001
      and February 2003. A total of 519 eyes of 493 patients were prospectively
      evaluated for PCO development during the 25-month period. All the patients were
      analyzed periodically with anterior segment retroillumination photography. The
      data provided were analyzed with chi-square method. RESULTS: The results between
      the two groups for PCO development were not statistically significant. However,
      there was a prominent opacification of the posterior capsule where the optic and
      haptic junction of IOL was positioned in some patients implanted with single
      piece IOL. During the follow-up period, no patients implanted with either three
      piece or single-piece acrylic IOL required Nd:YAG laser capsulotomy. CONCLUSIONS:
      Biocompatibility and reduced rate of PCO development are among the leading
      features of new generation IOLs. The intracapsular implantation of 5.5 mm optics
      acrylic IOLs resulted in decreased incidence of PCO and therefore greater patient
      satisfaction. Further studies investigating the effects of IOL optics, haptic
      structure and length, capsulorrhexis size, and IOL material and design features
      on PCO development will clarify the subject.

PMID- 15506599
TI  - Intraocular pressure variability in the anesthetized rat: a spectral analysis.
AB  - PURPOSE: Intraocular pressure (IOP) is a measure of the balance between the
      inflow and outflow of the aqueous humor, being in close relationship with the
      venous ocular blood flow. But the influence of the autonomic nervous system upon
      this variable is not well understood. One of the most frequently used
      mathematical tools for the evaluation of the autonomic nervous system in the
      frequency domain is the fast Fourier algorithm (FFT) applied to the analysis of
      heart rate (HR) and arterial blood pressure (BP). For these variables, a power
      spectrum has been built showing the major bands: very low frequency, lower
      frequency, and higher frequency (HF). The range of these bands depends on the
      animal species. In this study, the authors used FFT to analyze the variability of
      IOP in anesthetized rats. METHODS: BP and electrocardiogram were acquired at 2
      KHz in all animals before and following muscle blockade and artificial
      ventilation at the same frequency as the spontaneous ventilation. Also, in this
      last condition, IOP was recorded before and after the application of atropine in
      the eye. RESULTS: Results show three bands in the IOP spectrum, a similar profile
      to those observed in the HR and BP spectra, with HF band modified after atropine
      application DISCUSSION: The discussion calls attention to the influence of the
      autonomic nervous system on IOP and suggests the possibility of clinical
      application of this methodology on diagnosis and therapeutic efficacy.

PMID- 15506600
TI  - Screening for glaucoma in a general population with the non-mydriatic fundus
      camera and the frequency doubling perimeter.
AB  - PURPOSE: To evaluate the usefulness of non-mydriatic fundus camera (NMFu-camera)
      and frequency doubling perimeter (FDP) for detecting glaucoma in a general
      population. METHODS: This prospective observational multicenter study consisted
      in screening for glaucoma in the populations of three Belgian cities. Intraocular
      pressure (IOP) was measured with non-contact pneumo-tonometer (NCT) and
      applanation tonometry (AT) if NCT IOP was > or = 17 mmHg. Visual field was
      screened with FDP (C-20-5) and digitized optic disc photographs (ODPs) were taken
      with NMFu-camera. FDP was considered abnormal if at least one defective point was
      found. ODPs were graded as normal or glaucomatous by consensus of three glaucoma
      specialists. Optic disc and visual field results were matched per eye. Subjects
      with known ocular hypertension and/or treated primary open angle glaucoma were
      excluded from the analysis. RESULTS: A total of 1620 subjects were included in
      the study. Their mean age was 63.2 years. AT IOP was > 21 mmHg in 8.2%. A total
      of 98.1% of ODPs could be interpreted. Glaucomatous optic discs were detected in
      3.5% of the subjects. In this group only 24% had an AT IOP > or = 22 mmHg. FDP
      was abnormal in 44.5%. The sensitivity and specificity of FDP to identify
      patients with an optic disc graded as glaucomatous were 58.6% and 64.3%
      respectively. CONCLUSIONS: The combined use of the NMFu-camera and the FDP is a
      feasible method for an initial glaucoma mass screening. NMFu-camera may be a
      useful and quick method to screen for glaucomatous damage in a community. FDP in
      screening strategy was revealed to be not sensitive enough when setting the cut
      off value at one defective test location. IOP measurements were confirmed to be a
      poor tool to detect glaucomatous damage.

PMID- 15506601
TI  - The effects of cyclopentolate on intraocular pressure and retrobulbar
      hemodynamics in patients with pseudoexfoliation syndrome and pseudoexfoliation
      glaucoma.
AB  - PURPOSE: To evaluate the changes of intraocular pressure (IOP) and retrobulbar
      hemodynamics after cyclopentolate administration in patients with
      pseudoexfoliation syndrome and pseudoexfoliation glaucoma. METHODS: Eighteen
      patients with pseudoexfoliation syndrome and 18 patients with pseudoexfoliation
      glaucoma were enrolled in the study. After baseline measurements of IOP, the peak
      systolic velocity (PSV), end-diastolic velocity (EDV), and resistivity index (RI)
      of the ophthalmic, central retinal, and posterior ciliary arteries were
      investigated by color Doppler imaging. Then, 1% cyclopentolate was instilled in
      one eye of each subject. After 45 minutes of instillation of the cyclopentolate,
      the measurements of IOP and retrobulbar blood flow velocities were repeated. The
      results were compared with those of 20 age-matched normal subjects. RESULTS:
      Neither IOP nor retrobulbar blood flow velocities changed significantly in
      control subjects after cyclopentolate administration. IOP increased significantly
      after cyclopentolate instillation in pseudoexfoliation syndrome (p = 0.004).
      Retrobulbar blood velocities did not change significantly after the
      cyclopentolate in this group. In pseudoexfoliation glaucoma group, it was
      observed that basal mean IOP showed a statistically significant increase after
      cyclopentolate drop (p = 0.002). Although blood flow velocities of ophthalmic
      artery did not change significantly, PSV and EDV of the central retinal and
      posterior ciliary arteries decreased significantly (p < 0.05) and RI of the
      posterior ciliary artery increased significantly (p = 0.01) after cyclopentolate
      instillation. CONCLUSIONS: On the basis of our findings, pseudoexfoliation
      appears to be a predictive factor for an IOP rise after cyclopentolate. In
      pseudoexfoliation glaucoma patients, an increase of IOP after cyclopentolate
      could lead to a decreased retrobulbar blood flow. IOP must be rechecked after
      cyclopentolate administration in these patients to avoid further damage to the
      ganglion cells.

PMID- 15506602
TI  - Switching to latanoprost monotherapy for 24 weeks in glaucoma patients.
AB  - PURPOSE: To investigate the intraocular pressure lowering effect in glaucoma
      patients switched to latanoprost therapy from isopropyl unoprostone given as
      monotherapy or in combination with a beta-blocker. METHODS: Patients with primary
      open angle glaucoma or normal tension glaucoma treated with 0.12% isopropyl
      unoprostone as monotherapy or in combination with a beta-blocker were eligible
      for this single-center clinical study. Of the 51 patients (51 eyes) enrolled, 18
      were men and 33 were women aged 62.1 +/- 12.3 years (mean +/- SD). Twenty-two
      patients had primary open angle glaucoma, and 29 patients had normal tension
      glaucoma. Intraocular pressure was measured twice within 3 months prior to the
      switch, and the mean value was taken as the baseline. The patients were then
      switched to latanoprost (0.005%) monotherapy (once-daily administration), and
      changes in intraocular pressure were monitored. One physician measured
      intraocular pressure after 4, 8, 16, and 24 weeks of administration in this 24
      week study. RESULTS: The mean intraocular pressures were 16.0 +/- 2.4 mmHg at
      baseline, 13.7 +/- 2.3 mmHg after 4 weeks, 13.1 +/- 2.1 mmHg after 8 weeks, 13.6
      +/- 2.0 mmHg after 16 weeks, and 13.3 +/- 2.4 mmHg after 24 weeks. A significant
      decrease in intraocular pressure was noted at all time points in both groups
      (paired t-test, p < 0.0001), and the intraocular pressure lowering effect
      persisted through week 24 of administration (analysis of variance, p < 0.0001).
      CONCLUSIONS: Switching to latanoprost monotherapy elicits further reduction in
      intraocular pressure in patients with primary open angle glaucoma or normal
      tension glaucoma.

PMID- 15506603
TI  - Intraocular pressure, safety and quality of life in glaucoma patients switching
      to latanoprost from adjunctive and monotherapy treatments.
AB  - PURPOSE: To evaluate efficacy, safety and quality of life in ocular hypertensive
      or open-angle glaucoma patients changed to latanoprost from previous therapy.
      METHODS: A prospective, multicenter, active-controlled design in which qualified
      patients had their previous therapy substituted for latanoprost and were followed
      for at least three months. RESULTS: In 1068 patients, latanoprost was continued
      92% throughout the 36-month observation period. Latanoprost treatment reduced the
      intraocular pressure (1OP)(p < 0.001) when compared to previous monotherapies
      including: beta-blockers (-4.0 +/- 3.7 mmHg, 42%), alpha-antagonists (-3.9 +/-
      3.0 mmHg, 14%), miotics (-3.8 +/- 3.5 mmHg, 2%), or carbonic anhydrase inhibitors
      (CAI) (-3.8 +/- 3.6 mmHg, n = 16%), and adjunctive therapy including: beta
      blocker and CAI (-3.7 +/- 3.1 mmHg, n = 12%), alpha-agonist (-3.7 +/- 3.4 mmHg, n
      = 5%), or pilocarpine (-3.4 +/- 3.7 mmHg, n = 6%), or CAI and alpha-agonist (-4.6
      +/- 6.4 mm Hg, n = 2%)(p < 0.0017). The most common adverse event with
      latanoprost was ocular allergy (1.5% incidence). Patients showed a preference for
      latanoprost for many systemic and ocular quality of life measures on a non
      validated questionnaire (p < 0.05). CONCLUSIONS: In a clinical setting, patients
      who have their mono- and adjunctive therapy treatment substituted for latanoprost
      may on average experience reduced IOP, decreased side effects and increased
      quality of life measures.

PMID- 15506604
TI  - Intraocular pressure lowering efficacy of travoprost.
AB  - PURPOSE: To assess the intraocular pressure lowering effect of travoprost 0.004%
      in patients previously treated with another topical medication, and in previously
      untreated patients. METHODS: This 12-week, open-label trial in 1590 patients was
      conducted at 219 sites in Switzerland. Primary open-angle glaucoma and ocular
      hypertension patients discontinued prior medications, and instilled 1 drop of
      travoprost in each affected eye at 8 pm. Untreated patients were subdivided into
      2 groups: baseline IOP of > or = 21 mmHg, and baseline IOP of < or = 20 mmHg.
      Patients returned for follow-up visits at 1 and 3 months. The primary outcome was
      mean IOP change from baseline to follow-up. RESULTS: Of 626 patients previously
      on monotherapy, and 525 previously untreated or newly-diagnosed patients, 479 and
      423, respectively, completed 3 months of therapy. The mean changes from baseline
      at 1 month (mmHg +/- SD), by prior treatment group were: beta blocker, -4.9 (+/-
      3.6); latanoprost, -2.3 (+/- 2.8); alpha-agonist, -4.0 (+/- 3.7);
      dorzolamide/timolol fixed combination, -3.4 (+/- 3.9); topical CAI, -4.4 (+/-
      3.1); new IOP > or = 21 mmHg, -8.6 (+/- 4.4); new IOP < or = 20 mmHg, -4.4 (+/-
      3.0). (All changes from baseline were statistically significant (p < 0.0001).
      CONCLUSIONS: In patients previously treated with a single drug, travoprost
      decreased IOP to pressures below those achieved on prior therapy. In all groups,
      travoprost reduced mean IOP below 18 mmHg within 1 month of starting therapy, and
      control was maintained for at least 3 months. Overall, travoprost was safe and
      well-tolerated.

PMID- 15506605
TI  - Transpupillary thermotherapy in the management of choroidal metastases.
AB  - PURPOSE: To report the authors' experience in the use of infrared diode laser
      transpupillary thermotherapy in the management of selected posterior choroidal
      metastatic tumors. METHODS: Seven eyes of seven patients were treated using 810
      nm infrared diode laser. Spot sizes of 0.5 to 3 mm were selected, each lasting 1
      minute. When necessary, the treatment was repeated at 8- to 10-week intervals.
      Disappearance of the tumor was the main outcome measure. RESULTS: The primary
      sites of carcinomas were breast, prostate, and lungs. The largest basal diameters
      of ocular tumors varied between 5 mm and 10 mm and the thickness ranged between 2
      mm and 4.5 mm. A mean power of 612 mW was used in one to four treatment sessions.
      In six eyes the tumors were reduced into flat scars whereas in one case the tumor
      continued to grow necessitating external beam radiotherapy. In three eyes the
      visual acuity decreased and in three eyes the vision became better. In one eye
      the vision was restored after external beam radiotherapy with the disappearance
      of extensive subretinal fluid. There were no immediate postoperative
      complications. CONCLUSIONS: Transpupillary thermotherapy can be a reliable,
      convenient, and cost-cutting option in the management of small, solitary
      choroidal metastatic tumors with a thickness of less than 3.5 mm and which have
      minimal subretinal fluid. Although successful in terms of tumor control,
      treatment close to the fovea or optic nerve head may cause a permanent decrease
      in visual acuity.

PMID- 15506606
TI  - Spontaneous resolution of vitreomacular traction associated with diabetic macular
      edema.
AB  - PURPOSE: Little information is available about the natural history of
      vitreomacular traction (VMT) associated with diabetic macular edema. A few cases
      of spontaneous resolution of VMT associated with diabetic macular edema have been
      described, but have not been documented by optical coherence tomography (OCT).
      The authors report the spontaneous resolution of VMT associated with diabetic
      macular edema 1 month after the end of panretinal photocoagulation therapy (PRP).
      METHODS:  CASE REPORT: A 66-year-old woman presented with complicated
      proliferative diabetic retinopathy and diabetic macular edema associated with
      VMT, documented by OCT, in the right eye. Left eye examination showed complete
      PRP and ischemic maculopathy. PRP was immediately realized in the right eye in
      regard to the presence of complicated proliferative diabetic retinopathy.
      RESULTS: One month after the end of PRP, right eye visual acuity improved. OCT
      examination showed complete release of foveal posterior hyaloid traction, and
      significant reduction in foveal thickness. The follow-up was 1 year. At the end
      of follow-up, visual acuity slightly improved again; only a small residual foveal
      retinal thickening remained. CONCLUSIONS: The authors report spontaneous
      resolution of VMT associated with diabetic macular edema, probably facilitated by
      PRP, with concurrent reduction of macular thickness and visual improvement. As
      spontaneous resolution may occur in some eyes with diabetic macular edema
      associated with VMT, a period of observation after the end of the PRP may be
      considered prior to vitrectomy.

PMID- 15506607
TI  - Bilateral CNV associated with optic nerve drusen treated with photodynamic
      therapy with verteporfin.
AB  - PURPOSE: To report a case of bilateral choroidal neovascularization (CNV)
      associated with optic nerve drusen (OND) treated with photodynamic therapy (PDT)
      with verteporfin. METHODS: A 10-year-old girl with juxtapapillary CNV in the
      right eye and juxtapapillary and juxtafoveal CNV in the left eye associated with
      OND underwent PDT with verteporfin in both eyes. RESULTS: Visual acuity increased
      from 20/160 to 20/25 in the right eye and from 20/1000 to 20/25 in the left eye
      after two sessions of PDT and 2 years of follow-up. CNV showed no leakage after
      two PDT sessions in both eyes and no recurrence was observed. CONCLUSIONS:
      Subfoveal CNV is an uncommon complication of OND and excellent anatomic and
      functional results can be obtained with PDT.

PMID- 15506608
TI  - Optical coherence tomography imaging of surgical resolution of bilateral
      vitreomacular traction syndrome related to incomplete posterior vitreoschisis: a
      case report.
AB  - PURPOSE: To report a case of surgical resolution of bilateral vitreomacular
      traction syndrome related to incomplete posterior vitreoschisis as documented by
      optical coherence tomography (Stratus OCT, Carl Zeiss Meditec, Dublin, CA). CASE
      REPORT: In both eyes of a 72-year-old man with bilateral blurred vision, OCT
      examination disclosed a relevant increase in mean foveal thickness (right eye =
      714 microm; left eye = 757 microm) due to a vitreomacular traction syndrome. At
      the edges of the most highly elevated area of vitreo-macular traction, OCT scans
      showed a characteristic splitting of the hyperreflective signal in both eyes,
      usually identified as posterior vitreous cortex. Both eyes underwent vitrectomy
      with epiretinal membrane peeling. Postoperative OCT examination showed
      vitreomacular traction resolution in both eyes with an evident decrease in mean
      foveal thickness (right eye = 364 microm; left eye = 335 microm). Right visual
      acuity improved from 20/200 to 20/50; left visual acuity changed from 20/150 to
      20/40. CONCLUSIONS: OCT was a useful tool in identifying an unusual case of
      bilateral vitreomacular traction syndrome linked to incomplete posterior
      vitreoschisis and following a favorable course after surgical management.

PMID- 15506609
TI  - Late onset posttraumatic Propionibacterium acnes endophthalmitis.
AB  - PURPOSE: To report a case of late onset posttraumatic endophthalmitis secondary
      to Propionibacterium acnes infection. METHODS: Interventional case report.
      RESULTS: A 28-year-old man developed endophthalmitis 6 months after a penetrating
      trauma. The patient underwent pars plana lensectomy and vitrectomy along with
      injection of intravitreal antibiotics. Anaerobic cultures of the vitreous yielded
      P. acnes. Seven months after surgery, the eye was quiet with a best-corrected
      visual acuity of 20/60. CONCLUSIONS: This case emphasizes the importance of
      considering P acnes when treating patients with late onset posttraumatic
      endophthalmitis.

PMID- 15506610
TI  - Infliximab for the treatment of posterior uveitis with retinal neovascularization
      in Behcet disease.
AB  - PURPOSE: To report a case of posterior uveitis with retinal neovascularization in
      a patient with Behcet disease treated with infliximab. METHODS: A 50-year-old man
      with a history of recurrent relapses of ocular inflammation despite
      immunosuppressive therapy developed retinal neovascularization near the optic
      disk. The patient was treated with infliximab and followed up for 12 months.
      RESULTS: Retinal neovascularization regressed 8 months after the first anti-tumor
      necrosis factor (TNF) treatment and with six infusions of infliximab. The ocular
      inflammation resolved almost completely. CONCLUSIONS: The result suggests that
      anti-TNF therapy may be effective in the treatment of retinal neovascularization
      caused by panuveitis in Behcet disease.

PMID- 15506611
TI  - Retinal nerve fiber layer loss in pigment dispersion syndrome.

PMID- 15506612
TI  - Quantitative SPLITT fractionation of lagoon sediments.
AB  - In this work, SPLITT Fractionation (split flow thin cell) is used to sort
      hydrodynamically sedimented particles coming from the Sacca di Goro, a lagoon
      like system close to the Po River delta (Italy). First the possibility of
      performing quantitative mass separations with a SPLITT cell apparatus was checked
      on a standard silica sample of known particle size distribution (PSD).
      Environmental sediment samples and relative SPLITT sub-fractions were subject to
      Inductive Coupled Plasma--Atomic Emission Spectroscopy (ICP-AES) characterization
      for the following elements: Al, Fe, Cd, Cr, Cu, Ni, Mn, Pb and Zn. The
      distribution of these metals by particle size fractions has been investigated.
      The accuracy of the entire separation procedure has been also evaluated.

PMID- 15506613
TI  - Influence of air pollution on chronic obstructive respiratory diseases:
      comparison between city (Rome) and hillcountry environments and climates.
AB  - Chronic Obstructive Pulmonary Diseases (COPDs) constitute a social problem of
      widespread interest. These diseases increase slowly and constantly. Air pollution
      and its impact on public health continually repropose certain absolute
      priorities, such as the pin-pointing of strategies to control the pollution
      sources, the planning of observational studies and the epidemic control. This
      work shows that a climate marked by always windy weather and low humidity and
      with low chemical pollutant concentrations (Pietracupa; Molise, Italy) is
      connected to smaller prevalence of COPDs in comparison with big cities like Rome.
      Living in non-polluted areas, the benefits of a healthy climate in terms of an
      improvement in breathing and bronchial hyperactivity reduction, may only in part
      be backed up by epidemic evidence; however, they are a solid base on which to
      build definite research projects which can effectively validate it even from an
      experimental point of view supported by statistics.

PMID- 15506614
TI  - Long-term diffusive samplers for the indoor air quality evaluation.
AB  - Three kinds of diffusion samplers, conceived to perform long-term samplings in
      indoor sites are illustrated in this work. Two of them, in part deriving from the
      previous "Analyst for VOC" device, extend the field of application up to the semi
      volatile organic compounds (SVOC), PAHs and nicotine in particular. A third
      device, which employs a basic barium hydroxide solution as an absorbing medium,
      is proposed for the determination of carbon dioxide levels which indicate the air
      change quality in the indoor sites. Laboratory and field experiments, performed
      in order to assess the reliability of the proposed devices, are shown. A monthly
      monitoring campaign, performed at three private apartments in Rome and its
      outskirts highlights that the indoor pollution levels are a complex function of
      various concurrent and opposite factors, like external air pollution, internal
      sources, air change rate and sink effect of surfaces, which contribute to
      depletion phenomena through adsorption and/or decomposition processes.

PMID- 15506615
TI  - Carbonaceous aerosol in the breathable particulate matter (PM10) in urban area.
AB  - Carbonaceous material is a large fraction of urban aerosol and it is classified
      into Elemental Carbon (EC) and Organic Carbon (OC). EC particles are emitted from
      combustion sources. Because most combustion sources are anthropogenic and
      generally EC does not undergo chemical transformations, EC is a good indicator of
      primary anthropogenic primary pollution. OC particles species are emitted from
      primary emission sources either anthropogenic or biogenic sources. In this paper
      we have measured the ground concentration of Particulate Matter (PM), Total
      Carbon (TC), EC and OC in two Monitoring Stations in Rome. The first station is
      situated downtown Rome (near S.M. Maggiore Cathedral) where the traffic emission
      flux is strong. The second station is located in the inner a green park (Villa
      Ada Park): this site is not directly influenced by anthropogenic emissions. The
      results show that in Rome the TC contribution is about 30% of PM and the OC/EC
      vary between 0.5 and 1.5 according to the site we are considering. About the
      chemical particle composition the long-chain carboxylic have been identified as
      major constituent of organic aerosol and a range values are reported for two
      important compound class, the Polyciclic Aromatic Hydrocarbons and the nitro-PAHs
      wich are at very low levels.

PMID- 15506616
TI  - Photodegradation of azodyes: comparison of different catalytic systems and
      control of the effective mineralisation.
AB  - Three different azodyes were used as target molecules to test the efficiency of
      the photodegradation process catalysed by titanium dioxide under UV irradiation.
      A comparison of different catalytic systems was performed using the catalyst both
      free in solution (system I) and immobilised in a polymeric membrane (system II).
      Iron oxalate and a conducting polymer (polyaniline, PA) were added to the I and
      II systems respectively to check an eventual synergetic effect. The research
      evolved through three different steps involving each one the use of a different
      analytical method. Shortly, the UV spectrophotometry were preliminarily used to
      monitor the bleaching process and allowed to choose the best catalytic system,
      HPLC and GC/MS were used to monitor the appearance and disappearance of the
      photodegradation intermediates and, lastly, the effective mineralisation was
      tested by an indirect ICP (Inductively Coupled Plasma) determination of the
      produced carbon dioxide.

PMID- 15506617
TI  - Quantitative determination of volatile organic compounds (VOC) in milk by
      multiple dynamic headspace extraction and GC-MS.
AB  - A method for the accurate determination of volatile organic compounds (VOC) in
      milk samples has been developed and tested. It combines multiple dynamic
      headspace extraction with GC-MS. Absolute amounts of VOC in the liquid phase are
      obtained by determining the first order kinetic dependence of the stepwise
      extraction of the analytes and internal standards from the liquid matrix.
      Compounds released from milk were collected on a train of traps filled with
      different solid sorbents to cover all components having a number of carbon atoms
      ranging from 4 to 15. They were analysed by GC-MS after thermal desorption of VOC
      from the collecting traps. Quantification of VOC in milk was performed using
      deuterated compounds as internal standards. The method was used to follow
      seasonal variations of monoterpenes in goat milk and to detect the impact of air
      pollution on the quality of milk.

PMID- 15506618
TI  - Identification of compounds in wine by HPLC-tandem mass spectrometry.
AB  - In this work several compounds were detected in wines by HPLC-tandem mass
      spectrometry. In particular cinnamic and benzoic acids, tyrosol, apigenin-7
      glucoside and luteolin-7-glucoside were identified and quantified in Italian
      wines. Red wines show bigger amount of cinnamic and benzoic acids than white
      wines. tyrosol is in bigger amount with respect to two flavones: luteolin-7
      glucoside and apigenin-7-glucoside. These last two flavones are only in some
      wine, but it can be important to detect the presence of different substances in
      small amount to be able to characterize a wine.

PMID- 15506619
TI  - Data quality of PAH determinations in environmental monitoring.
AB  - The sources of uncertainty affecting measurements of pollutants include sample
      collection, handling and stocking, and analytical procedure. With regard to
      chemical analysis, MS detection offers a series of advantages for resolving
      complex mixtures and identify and quantify analytes present at very small
      extents. Nevertheless, it presents some problems of reproducibility, which can
      affect the quality of quantitative data. PAH represent key-compounds among
      atmospheric pollutants and are usually evaluated by means of dedicated methods
      comprising MS detection. Based upon the above considerations, an analytical
      method has been standardized, suitable for determining PAH in atmospheric
      aerosols and diesel particulate exhausts. To test the procedure, both diesel
      particulate and urban aerosol NIST reference materials (SRM-2975 and SRM-1649A,
      respectively) have been processed and the results have been compared with
      certified and/or literature data. The results obtained are shortly discussed.

PMID- 15506620
TI  - Determination of phenolic acids in olive oil by capillary electrophoresis.
AB  - A CZE method for the separation and quantitation of phenolic acids (cinnamic,
      syringic, p-coumaric, vanillic, caffeic, 3,4-dihydroxyphenylacetic,
      protocatechuic), extracted from extra virgin olive oil, was developed. The sample
      preparation involved the LLE and SPE extraction methods. CE separation was
      performed in a fused silica capillary of I.D.= 50microm using as a BGE 40 mM
      borate buffer at pH=9.2. The separation voltage was 18kV with corresponding
      current of 27-28 microA. Detection was accomplished with UV-detector at
      lambda=200nm. The proposed method was fully validated. A good repeatability of
      migration time (RSD% ranged from 0.81 to 1.63) and of corrected peak area (RSD%
      from 2.89 to 5.77) was obtained. The linearity of detector response in the range
      from 5 to 50 ppm was checked, obtaining the correlation coefficient R2 values in
      the range: 0.9919-0.9997. Some phenolic acids in real oil samples were detected
      and quantified with the proposed method.

PMID- 15506621
TI  - Remote sensing measurements for evaluation of air quality in an urban area.
AB  - The Differential Optical Absorption Spectrometry (DOAS) is a remote-sensing
      technique finding greater consents in these last years. The analytical principle
      of the DOAS system is based on the light absorption in the near-UV and Vis
      regions of those pollutants with fine vibrational structures such as SO2, NO2,
      O3, nitrous acid, formaldehyde, benzene, toluene, etc.. The relationship among
      the adsorbed light intensity and the xompound concentrations is ruled by the
      Lambert-Beer's law. The DOAS analysis allows to study and to interpretate the
      complex mechanisms of the formation and transformation of the pollutants and
      particularly of those of secondary origin. In this paper we have reported and
      discussed the behaviors of NO2, O3, HNO2, formaldehyde, benzene and toluene
      measured by this system during the 2000--2003 period in the Rome area (an area
      highly influenced by anthropogenic sources) and in Pietracupa (Molise) area
      (considered as remote site). The results show how the DOAS system highlight very
      well the secondary pollution evolution; this, described by the profiles of NO2
      and O3 being at the same time products and precursors of the photochemical smog,
      is not influenced by the emission flow intensity and consequently assumes
      homogeneous values in the whole urban area.

PMID- 15506622
TI  - Gas chromatographic--mass spectrometric determination of phenylacetic acid in
      human blood.
AB  - Phenyl acetic acid, a metabolite of 2-phenyl ethylamine, acts as a neuromodulator
      in the nigrostriatal dopaminergic pathway stimulating the release of dopamine.
      The evaluation of phenyl acetic acid concentration in the biological fluid
      reflects phenyl ethylamine levels thus allowing the assessment of the modulatory
      role of this endogenous substance. Changes in biological fluids levels of 2
      phenylethylamine and/or in its metabolite have been reported in affective
      disorders, such as depression and schizophrenia. Recently, the occurrence of the
      "attention deficit hyperactivity syndrome" has been frequently reported in
      childhood population and involvement of dopaminergic dysfunction in this disease
      has been suspected. A fast, reliable and reproducible method for the
      determination of phenyl acetic acid in human blood, is therefore needed in order
      to have a screening tool for monitoring both healthy childhood population and
      suspected "attention deficit hyperactivity syndrome" patients. The gas
      chromatographic-mass spectrometric method here described makes use of a
      deuterated internal standard in order to overcome problems related to the lack of
      reproducibility often encountered when a derivatization step is performed.

PMID- 15506623
TI  - GC-MS in space research: decoding complex isothermal chromatograms recovered from
      space missions.
AB  - An analytical procedure is described to study GC-MS isothermal chromatograms
      simulating those recovered from space missions: in fact GC plays a predominant
      role in space missions devoted to characterizing the chemical composition of
      extra-terrestrial atmospheres. SIM (selected ion monitoring) detection was used
      for monitoring selected chemical classes: a simplified chromatogram can be
      obtained giving information on the chemical composition of the complex mixture.
      Since only isothermal GC chromatograms are allowed by flight constraints, a time
      axis transformation is required to make them homogeneous: i.e., constant
      retention increments for CH2 additions in terms of a homologous series. The order
      in the linearized chromatogram can be simply singled out with a chemometric
      approach based on the study of the Autocovariance Function (ACVF) computed on the
      digitized chromatogram: the plot of the experimental autocorrelation function
      (EACF) shows well-shaped peaks if constant interdistances are repeated in
      different regions of the chromatogram. The method was applied to standard
      mixtures representative of planetary atmospheres--hydrocarbons, nitriles and
      oxygenated compounds with between 3 and 12 carbon atoms--analyzed in flight
      simulating conditions. The coupling of the selectivity of SIM detection with the
      interpretation power of the EACF procedure proves to be a powerful tool for
      interpreting data recovered from space missions: the chemical composition of the
      mixture can be identified by handling the raw SIM chromatograms.

PMID- 15506624
TI  - Characterization of polycyclic aromatic hydrocarbons and carbonyl compounds in
      diesel exhaust emissions.
AB  - Exhaust emissions from a recent model heavy-duty diesel vehicle (city bus) in a
      chassis dynamometer were measured during a transient driving cycle. Particle
      bound polycyclic aromatic hydrocarbons (PAHs) and gaseous carbonyls, substances
      that create health hazards and are, as yet, unregulated were collected, the
      former on filters and the latter on dinitrophenylhydrazine (DNPH)-coated silica
      cartridges and analysed by GC-MS and HPLC, respectively. PAH emission rates
      decreased with the number of benzene fused rings. They averaged 0.2 mg km(-1) for
      a total of 11 PAHs ranging from fluoranthene to benzo(ghi)perylene. Fluoranthene
      and pyrene accounted for 90% of total PAHs. The sum of emission rates of C1
      approximately C6 carbonyls averaged 174 mg km(-1), even if formaldehyde alone
      represented approximately 70% of the total carbonyl mass, followed by
      acetaldehyde (13%). Results obtained were compared with emission data reported in
      previous studies.

PMID- 15506625
TI  - NH2-SEP-PAK cartridges for enrichment of Aromatic Sulfur Compounds from sea
      water: determination by GC-FID and GC-MS.
AB  - The Aromatic Sulfur Compounds (ASCs) are considered as "markers" of the crude oil
      age. In this frame, we have considered ASCs as "markers" of remote crude oil sea
      water pollution for their chemical characteristics, good solubility in water and
      resistance to the biodegradation. Gas chromatography of ASCs in distilled water
      and sea water samples has been performed after adsorption from a 80 mL water
      sample on to a cartridge containing 100 mg NH2-bonded porous silica. The ASCs are
      desorbed with 2 mL acetone-trichloromethane (1:1), which is concentrated and
      analysed by GC-FID or GC-MS in SIM mode. The average recovery of 0.1 microg mL(
      1) of each ASC from distilled water and 0.04-0.2 microg mL(-1) from sea water
      samples is > or = 96.3% with a standard deviation < or = 2.2. The limits of
      detection are 0.06-0.05 ng mL(-1) for thiophen-2-carboxaldehyde and
      benzothiophene, and 0.006-0.004 ng mL(-1) for dibenzothiophene and thiantrene in
      GC-FID whereas they are 0.02 ng mL(-1) for thiophen-2-carboxaldehyde and
      benzothiophene, and 0.003 ng mL(-1) for dibenzothiophene and thiantrene in GC-MS
      (SIM) with a relative standard deviation < or =7.

PMID- 15506626
TI  - Improved analysis of Polycyclic Aromatic Hydrocarbons in atmospheric particulate
      matter by HPLC-fluorescence.
AB  - An improved method is reported for determination of Polycyclic Aromatic
      Hydrocarbons (PAHs) in atmospheric particulate matter by HPLC-FLD. The sampling
      step (air volume collected during each sampling period varies in the range 10/13
      m3) is carried out by means of a medium-flow pumping system (15 L min(-1)) on a
      glass fiber filter (47 mm diameter) placed as collecting substrate in the
      sampling-cassette. After sampling, the filter is extracted with 3 ml of
      acetonitrile in an ultrasonic bath for 30 minutes. As for extraction of PAHs from
      loaded filters a new criterion here is proposed to evaluate the recovery
      efficiency of PAHs from the sample, instead of the usual spiking method of
      standard solution. The extract was then reduced to 100 microL and analysed by
      HPLC-FLD on line spectra system. The method is rapid (about one hour for
      extraction and analysis), reproducible and enables to measure with good accuracy
      the atmospheric concentration of benzo(b)fluoranthene (BbF), benzo(k)fluoranthene
      (BkF), benzo(a)pyrene (BaP), benzo(ghi)perylene (BghiP), carcinogenic compounds
      always present in the urban airborne particulate matter. So it is useful for
      routine pollution studies and suitable to substitute the official method used
      now. Monthly average air concentrations, for the four PAHs above mentioned,
      measured in Rome from July 2001 to June 2002, are reported.

PMID- 15506627
TI  - Paper chromatographic and paper elettrophoretic study of the solution chemistry
      of Tc-99m-methylendiphosphonate and of Tc-99m-dimercaptosuccinate for improving
      the tumour-affinity of Tc-99m during scintigraphic imaging of cancer.
AB  - In order to find the conditions under which Tc-99m-methylenediphosphonate (Tc-99m
      MDP) and Tc-99m(V)-dimercaptosuccinate (Tc-99m(V)-DMSA) may become tumour-seeking
      agents, leaving healthy organs free from the radionuclide uptake, the solution
      chemistry of these radiopharmaceuticals was studied by paper chromatography and
      paper electrophoresis in distilled water, in physiological saline, in NAHCO3, and
      ascorbic acid solutions. Both radiopharmaceuticals are anionic in the
      radiopharmaceutical solution but get easily hydrolysed to form cationic Tc-99m
      species which concentrates in healthy bone and in some bone metastases. Tc-99m
      (V)-DMSA being more stable remains long in the blood pool giving undesirable
      presence of the radionuclide in lung, heart and kidneys, in addition to its
      reduced uptake in bone metastases and in some primaries. We are trying to
      eliminate these drawbacks of healthy organ uptake of Tc-99-m(V)-DMSA not only to
      get a clean scintigraphic image of the tumour with this radiopharmaceutical but
      to extend its formulation, thus obtained, to prepare radiopharmaceutical with Re
      188, which is the higher homologue of Tc-99m, for systemic therapy of cancer.
      Essentially similar solution chemistry of both radiopharmaceuticals suggests that
      like Tc-99m-MDP, technetium-99m-dimercaptosuccinate is also a complex of
      tetravalent Tc-99m and not of pentavalent Tc-99m as so far supposed to be.

PMID- 15506628
TI  - Sustainable chemistry: signal for innovation or only slogan?

PMID- 15506629
TI  - Principles and perspectives.
AB  - BACKGROUND, AIM AND SCOPE: With respect to the enormous increase of chemical
      production in the last decades and the tens of thousands of individual chemicals
      on the market, the permanent improvement of chemical management is a permanent
      target to achieve the goals of sustainable consumption and production set by the
      WSSD in Johannesburg 2002. MAIN FEATURES: Several approaches exist to describe
      sustainability of chemistry. However, commonly agreed criteria are still missing.
      There is no doubt that products of modern chemistry help to achieve important
      goals of sustainability and that significant improvements have occurred regarding
      direct releases from production sites, but several facts demonstrate that
      chemistry is far from being sustainable. Still too many chemicals exhibit
      hazardous characteristics and pose a risk to health and environment. Too many
      resources are needed to produce chemicals and finished products. RESULTS AND
      CONCLUSION: Therefore, a strategy for sustainability of chemistry should be
      developed which comprises the following main elements: 1. Sustainable chemicals:
      sustainable chemical management includes a regulatory framework which makes no
      difference between new and existing chemicals, contains efficient information
      flow through the supply chain which allows users to handle chemicals safely and
      offers an authorisation procedure and/or an efficient restriction procedure for
      substances of high concern. This regulatory scheme should promote the development
      of inherently safe chemicals. 2. Sustainable chemical production: Sustainable
      chemical production needs the development and implementation of emerging
      alternative techniques like selective catalysis, biotechnology in order to
      release less CO2 and less toxic by-products, to save energy and to achieve higher
      yields. Information exchange on best available techniques (BAT) and best
      environmental practices (BEP) may help to promote changes towards more
      sustainability. 3. Sustainable products: An integrated product policy which
      provides a framework for sustainable products promotes the development of
      products with a long-term use phase, low resource demand in production and use,
      low emission of hazardous substances and properties suitable for reuse and
      recycling. This may be promoted by eco-labelling, chemical leasing concepts and
      extended information measures to enhance the demand of consumers and various
      actors in the supply chain for sustainable products. RECOMMENDATION AND
      PERSPECTIVE: Important tools for the promotion of sustainable chemistry are the
      abolition of barriers for innovation in legislation and within the chemical
      industry, more transparency for all users of chemical products, a new focus on
      sustainability in education and research, and a new way of thinking in terms of
      sustainability.

PMID- 15506630
TI  - Ecotoxicological characterisation and classification of existing chemicals.
      Examples from the ICCA HPV initiative and comparison with other existing
      chemicals.
AB  - GOAL, SCOPE AND BACKGROUND: In 1998, the International Council of Chemical
      Associations (ICCA) launched a global initiative to investigate more than 1,000
      HPV chemicals (High Production Volume, > or = 1,000 t/a) within the refocused
      OECD HPV Chemicals Programme. Up to the OECD SIDS Initial Assessment Meeting in
      April 2004 (SIAM 18) 147 ICCA dossiers (ca. 230 CAS-No) have been assessed based
      on a harmonised data set. The environmental profile and an ecotoxicological
      characterisation of these chemicals are presented here. Data for acute aquatic
      toxicity were correlated among each other, as well as data for fish (LC50, LD50)
      and rodents (LD50). The data for acute aquatic toxicity are compared with other
      existing chemicals. METHODS: Data of the ICCA HPV chemicals from the OECD SIAM 11
      18 are presented for: log Kow (as an indicator for bioaccumulation potential),
      biodegradation, acute aquatic toxicity and availability of long-term toxicity
      data. Correlation analysis was performed with log transformed data and a linear
      regression model was fitted to the data, if a significant correlation was found.
      Acute toxicity for fish and acute oral toxicity for rodents were correlated on a
      molar basis. Acute aquatic toxicity of the chemicals is compared with data from
      BUA reports 1-234 and a random EINECS sample (Knacker et al. 1995). RESULTS AND
      DISCUSSION: According to the dossier information, 71 of the 147 ICCA chemicals
      are not 'readily biodegradable', 21 have a log Kow > or = 3, and 44 are 'toxic'
      (LC/EC50 < or = 10 mg/L) or 'very toxic' (LC/EC50 < or = 1 mg/L) to aquatic
      organisms. For 77, only the base set (acute fish, Daphnia and algae) is
      available, for the rest at least one long-term test (fish or Daphnia) is
      available and three tests for a mere 14 others. Based on the data presented, the
      SIAM gives recommendations for Environment and Human Health. 22 chemicals have
      been identified as a 'candidate for further work' for Environment and 16 for
      Human Health. The highest correlation coefficient was obtained correlating fish
      and Daphnia (r2 = 0.79). LC50 (fish) is significantly correlated with LD50
      (rodent), but data are widely scattered. The correlation is not improved after
      transforming LC50 (fish) to LD50 (fish), using BCF QSAR. Based on acute aquatic
      toxicity, 25.1% of the chemicals from the BUA reports 1-234 are classified as
      'very toxic' (LC/EC50 < or = 1 mg/L). This proportion is 2.5-fold higher than the
      ICCA HPV chemicals and 1.4-fold higher than the random EINECS sample.
      CONCLUSIONS: Correlation coefficients for aquatic toxicity data are rather
      uniform (0.57-0.79) compared with literature data, but also the best correlation
      was observed between fish and Daphnia. Because the scatter around the regression
      lines is still considerable, simple predictions of ecotoxicity between species
      are not possible. Correlation of LC50 (fish) and LD50 (rodent) indicates that
      toxicity is different. Surprisingly, the correlation of fish and rodent toxicity
      is not improved by transforming LC50 values to internal LD50s. The selection of
      ICCA chemicals by market significance (production volume) leads to a
      classification of toxicity, which is more comparable to a random sample of EINECS
      chemicals than to German BUA chemicals. The latter were chosen for concern (for
      Environment or Human Health). RECOMMENDATIONS AND OUTLOOK: Of 147 dossiers
      assessed between SIAM 11-18, ca. 75% were sponsored by the three following
      countries: Germany (42), USA (37) and Japan (33). The current output is about 50
      dossiers per year (70-100 CAS-No), but a trend for an increase of output is
      noticeable. Industry, national authorities, and OECD work on a further
      development to speed up the output. The number of chemicals with 'low priority
      for further work' and the work recommended for the 'candidates' (mainly exposure
      assessment) indicate that the data presented were adequate for an initial hazard
      assessment according to OECD requirements. From the ICCA HPV list (n = 880, state
      of 1999) 44% of the chemicals have data available to cover all SIDS endpoints for
      Environment and only 33% for Human Health (Allanou et al. 1999). This indicates
      the importance of the Initiative to provide information on existing chemicals.
      The authors agree with the expectation "...that the scientific information
      provided by this global initiative will be considered as an internationally
      accepted and harmonised basis for further steps of chemicals management." (ICCA
      2002 b).

PMID- 15506631
TI  - Screening and scenarios of traffic emissions at Trier, Germany.
AB  - SCOPE AND BACKGROUND: In the course of the European Council Directive on
      permissible air pollutant limit values, valid starting from 2005 there is an
      urgent call for action, particularly for fine dust (PM10). Current investigations
      (Junk & Helbig 2003, Reuter & Baumuller 2003) show that the limit values in
      certain places in congested areas are exceeded. Only if it is possible to locate
      these Hot Spots purposeful measures to reduce the ambient air pollution can be
      conducted. For an efficient identification of these Hot Spots numerical computer
      models or establishing special measurements networks are too expensive. Using the
      statistical model STREET 5.0 (KTT 2003) a cost-effective screening of the air
      pollution situation caused by the traffic can be done. METHODS: STREET is based
      on the 3-dimensional micro-scale non-hydrostatic flow- and dispersion model
      MISCAM (Eichhorn 1989). The results of over 100.000 different calculations with
      MISCAM are stored in a Database and used to calculate the emissions with STREET.
      In collaboration with the city council of Trier more than 150 streets were
      investigated, mapped, and calculated. A special urban climate measuring network
      supplies the necessary meteorological input data about the wind field and
      precipitation events in the valley of the Moselle. Information about road width
      and road orientation as well as building density was derived from aerial
      photographs. Traffic censuses and mobile air pollutants measurements supplied the
      remaining input data. We calculated the mean annual air pollutant concentrations
      for NO2, CO, SO2, O3, benzene as well as PM10. RESULTS: A comparison of the model
      results with the values obtained from the stations of the central emission
      measuring network of Rhineland-Palatinate (ZIMEN, annual report 2002) shows very
      good agreements. The model was not only used to calculate the annual air
      pollutant but also for urban planning and management. The absolute level of the
      air pollutant is mainly dependent on the amount of traffic in the street canyons.
      Therefore four different case-scenarios with varying quantity of traffic were
      calculated and interpreted for each street. The results of the calculation show
      that on the basis of the mean values for both NO2 and benzene, it is not to be
      expected that the limits PERSPECTIVES: Furthermore the model can be used to find
      the maximum tolerable numbers of cars for a street without exceeding the air
      pollutant thresholds.

PMID- 15506632
TI  - Using multimedia modeling to expedite site characterization.
AB  - GOAL, SCOPE AND BACKGROUND: This paper uses two case studies of U.S. Department
      of Energy nuclear weapons complex installations to illustrate the integration of
      expedited site characterization (ESC) and multimedia modeling in the remedial
      action decision making process. CONCEPTUAL SITE MODELS, MULTIMEDIA MODELS, AND
      EXPEDITED SITE CHARACTERIZATION: Conceptual site models outline assumptions about
      contaminates and the spatial/temporal distribution of potential receptors.
      Multimedia models simulate contaminant transport and fate through multiple
      environmental media, estimate potential human exposure via specific exposure
      pathways, and estimate the risk of cancer and non-cancer health outcomes. ESC
      relies on using monitoring data to quantify the key components of an initial
      conceptual site model that is modified iteratively using the multimedia model.
      CASE STUDIES: Two case studies are presented that used the ESC approach: Los
      Alamos National Laboratory (LANL) and Pantex. LANL released radionuclides,
      metals, and organic compounds, into canyons surrounding the facility. The Pantex
      Plant has past waste management operations which included burning chemical wastes
      in unlined pits, burying wastes in unlined landfills, and discharging plant
      wastewaters into on-site surface waters. CONCLUSIONS: The case studies indicate
      that using multimedia models with the ESC approach can inform assessors about
      what, where, and how much site characterization data needs to be collected to
      reduce the uncertainty associated with risk assessment. Lowering the degree of
      uncertainty reduces the time and cost associated with assessing potential risk
      and increases the confidence that decision makers have in the assessments
      performed.

PMID- 15506633
TI  - Cost-benefit analysis as a tool for decision making in environmental projects.
      Application to a reduction of dioxin emissions in Tarragona Province, Spain.
AB  - BACKGROUND, AIM AND SCOPE: The Damage-Function method is an efficient tool
      recently used in decision-making processes concerning environmental management.
      It is based on finding the relation between the origin of an environmental
      charge, and its impact on human health and the environment. The aim of the
      present investigation was to assess the positive impacts, also called benefits,
      of changes in environmental quality, and the economic viability of an industrial
      project on reduction of PCDD/F emissions. It has been developed with monetary
      criteria of two worldwide ambits: USA and European-Union countries. METHODS: The
      current study is a continuation of a previous investigation in which Substance
      Flow Analysis and Control Analysis Techniques were used to identify and to
      analyze all main flow values of PCDD/Fs inside the system of Tarragona Province
      (Spain). In the present study, Cost-Benefit Analysis (CBA) has been employed. The
      benefits derived from a minimization in the incidence of cancer due to a
      reduction in the emission of PCDD/Fs have been evaluated considering the value of
      a statistically saved life (VSL). Statistical analysis about uncertainty has also
      been incorporated. Here, the Monte Carlo simulation technique has been used.
      RESULTS: It is shown that CBS results depend firstly on the kind of VSL used. In
      fact, the differences between the decisions as a result of applying monetary
      criteria in USA and EU can be explained by differences between VSL values.
      CONCLUSION AND RECOMMENDATION: It is concluded that, for prices estimated in
      Euros, the emission cleaning project in the industrial plant is not feasible
      under any circumstance. However, although CBA seems to be a good analytical
      method, the final decision corresponds to the managers, who must weigh up not
      only the monetary criteria, but factors such as social questions.

PMID- 15506634
TI  - Changes in toxicity and genotoxicity of industrial sewage sludge samples
      containing nitro- and amino-aromatic compounds following treatment in bioreactors
      with different oxygen regimes.
AB  - GOALS, SCOPE AND BACKGROUND: From 2005, deposition of organic waste will be
      banned in Sweden. Likewise, in Germany and Austria, similar bans are being
      planned, and further countries will probably follow. Thus, there is a need to
      develop new methods and to refine established techniques for sludge management in
      the whole of the European Union. For this end, there is also an urgent need for
      appropriate ecotoxicological approaches to elucidate and assess the hazard
      potential of sewage sludge. Therefore, the present study was designed to assess
      the capacity of various established sludge treatment methods using different
      oxygen regimes to degrade recalcitrant nitro-substituted organic compounds and
      reduce their toxicity. Sewage sludge samples from a wastewater treatment plant in
      Sweden (Cambrex Karlskoga AB, industrial area Bjorkborn) receiving wastewater
      from industries manufacturing pharmaceutical substances, chemical intermediates
      and explosives were processed with different sludge treatment methods. Among
      other treatment methods, bioreactors (for anaerobic and aerobic sludge treatment)
      were used. In the present investigation, a battery of in vitro bioassays was
      employed to compare the cytotoxic and genotoxic potentials of different fractions
      of sludge samples in order to elucidate whether the treatments were suitable to
      reduce the toxicity of the sludge. METHODS: In order to investigate the
      cytotoxicity of the extracts of treated and untreated sludge samples, the acute
      cytotoxicity test with the permanent cell line RTL-W1 was used. Genotoxicity was
      tested by means of the comet assay (single cell gel electrophoresis) with RTL-W1
      cells, and mutagenicity was assessed with the Ames test using the Salmonella
      typhimurium strains TA98, TA98NR and TA100. Sludge toxicity was tested in
      different fractions of organic extracts produced by acetone and hexane
      extractions. The subsequent clean-up procedure (silica gel chromatography and
      elution with hexane and dichloromethane) resulted in two fractions, a lipophilic
      hexane-fraction and a semi-lipophilic dichloromethane-fraction. For the
      genotoxicity and mutagenicity tests, these fractions were reunited at equal
      ratios. RESULTS AND DISCUSSION: The acute cytotoxicity test with RTL-W1 cells
      revealed a high cytotoxic potential for the semi-lipophilic DM-fractions of all
      sludge samples with NR50 values (= effective concentration for 50% cell death in
      the neutral red test) from 8.9 up to 20 mg sludge d.w./ml medium. A low cytotoxic
      potential for the hexane fractions of the untreated sludge samples (NR50 400 to >
      400 mg sludge d.w./ml medium) was observed, whereas the hexane fractions of the
      treated sludge samples showed elevated cytotoxicity increasing further with
      treatment in the bioreactors. The comet assay indicated that three out of eight
      of the reunited fractions had a significant genotoxic potential. Whereas the
      genotoxic potential of one sample treated anaerobically was very high with an
      induction factor of 11.6, a similar sample (taken from the same anaerobic reactor
      four months later) and one untreated sample showed lower potentials. The samples
      treated in another anaerobic bioreactor as well as the samples treated
      aerobically showed no genotoxic potential. Results indicate that aerobic
      treatment was basically adequate for reducing the genotoxicity of the sludge,
      whereas anaerobic treatment was only partly useful for reduction of genotoxicity.
      The Ames test revealed a very high mutagenic potential for the reunited fractions
      of the untreated sludge samples with strain TA98 (maximum induction factors
      (IFmax) up to 45) and a relatively high potential for one of the samples treated
      aerobically (S2, IFmax = 18 (TA98, S9-)), thus documenting the suitability of
      both anaerobic and aerobic treatments to reduce the mutagenicity of the samples,
      however, with the aerobic treatment being less effective. CONCLUSIONS: Overall,
      none of the microbiological treatments for wastewater sludge in bioreactors was
      found to be ideal for general toxicity reduction of the sludge samples. Whereas
      cytotoxicity of the sludge increased or levelled off in most cases following
      either treatment, genotoxicity both increased or decreased after anaerobic
      treatment, depending on the specific sample. However, mutagenicity could
      generally be reduced by anaerobic treatment and, to a lesser degree, by aerobic
      treatment. RECOMMENDATIONS AND PERSPECTIVES: The complex modification of the
      diverse damage potentials of sludge sample extracts by use of an in vitro biotest
      battery following treatment for toxicity reduction in bioreactors showed that
      considerations of different toxicological endpoints is essential for an adequate
      hazard assessment. Whereas in the case of cytotoxicity reduction, the reactors
      proved ineffective, mutagenicity could be reduced significantly at least in some
      cases in this case study.

PMID- 15506635
TI  - Assessing the efficacy of dredged materials from Lake Panasoffkee, Florida:
      implication to environment and agriculture. Part 1: Soil and environmental
      quality aspect.
AB  - BACKGROUND, AIMS AND SCOPE: Dredged materials because of its variable but unique
      physical and chemical properties are often viewed by society and regulators as
      pollutants, but many have used these materials in coastal nourishment, land or
      wetland creation, construction materials, and for soil improvement as a soil
      amendment. Environmental impact assessment is an important pre-requisite to many
      dredging initiatives. The ability to reuse lake-dredge materials (LDM) for
      agricultural purposes is important because it reduces the need for off-shore
      disposal and provides an alternative to disposal of the materials in landfills.
      Additional research on disposal options of dredged materials are much needed to
      supply information on criteria testing and evaluation of the physical and
      chemical impacts of dredged materials at a disposal site, as well as information
      on many other aspects of dredging and dredged material disposal. While
      preliminary efforts are underway to provide information to establish criteria for
      land disposal, testing procedures for possible land disposal of contaminated
      sediments are still in their developing stage. The objective of this study (Part
      1) was to quantify the effect of applied LDM from Lake Panasoffkee (LP), Florida
      on soil physico-chemical properties (soil quality) at the disposal site. This
      series of two papers aims at providing assessment of the efficacy of lake-dredged
      materials from LP especially its implication to environment (soil quality, Part
      1) and agriculture (forage quality and pasture establishment, Part 2). METHODS:
      The experimental treatments that were evaluated consisted of different ratios of
      natural soil (NS) to LDM: LDM0 (100% NS:0% LDM); LDM25 (75% NS:25% LDM); LDM50
      (50% NS:50% LDM); LDM75 (25% NS:75% LDM); and LDM100 (0% NS:100% LDM). Field
      layout was based on the principle of a completely randomized block design with
      four replications. The Mehlich 1 method (0.05 N HCl in 0.025 N H2SO4) was used
      for chemical extraction of soil. Soil P and other exchangeable cations (Ca, Mg,
      K, Al, and Fe) were analyzed using an Inductively Coupled Plasma (ICP)
      Spectroscopy. The effects of dredged materials addition on soil quality and
      compaction were analyzed statistically following the PROC ANOVA procedures.
      RESULTS AND DISCUSSION: Sediments that were dredged from LP have high CaCO3
      content (82%) and when these materials were incorporated into existing topsoil
      they would have the same favorable effects as liming the field. Thus, sediments
      with high CaCO3 may improve the physical and chemical conditions of subtropical
      sandy pastures. The heavy and trace metal contents of LDM were below the probable
      effect levels (PEL) and threshold effect levels (TEL). Average values for Pb, Zn,
      As, Cu, Hg, Se, Cd, and Ni of 5.2 +/- 1.3, 7.0 +/- 0.6, 4.4 +/- 0.1, 8.7 +/- 1.2,
      0.01 +/- 0.02, 0.02 +/- 0.02, 2.5 +/- 0.1, and 14.6 +/- 6.4 mg kg(-1),
      respectively, were below the TEL and the PEL. TEL represents the concentrations
      of sediment-associated contaminants that are considered to cause significant
      hazards to aquatic organisms, while, PEL represents the lower limit of the range
      of the contaminant concentrations that are usually or always associated with
      adverse biological effects. As such, the agricultural or livestock industry could
      utilize these LDM to produce forages. LDM should be regarded as a beneficial
      resource, as a part of the ecological system. Addition of LDM had significant (p
      < or = 0.001) effects on soil physico-chemical properties and soil quality.
      Compared with the control plots, the soils in plots amended with LDM exhibited:
      (1) lower degree of soil compaction; (2) an increase in soil pH, Ca, and Mg; (3)
      decrease in the levels of soil Mn, Cu, Fe, Zn, and Si; and (4) no significant
      change in the level of Na in the soil. Results have shown the favorable influence
      that LDM had on soil compaction. The treatment x year interaction effect was not
      significant, but the average soil compaction varied widely (p < or = 0.001) with
      LDM application. In 2002 and 2003, soil compaction of plots was lowered
      significantly as a result of LDM additions. The least compacted soils in 2002 and
      2003 were observed from plots with LDM75 with mean soil compaction of 300 x 10(3)
      and 350 x 10(3) Pa, respectively. CONCLUSION: Beneficial uses of dredged
      materials from LP, Florida are both economical and environmental. Often these
      materials can be obtained at little or no cost to the farmers or landowners in
      south Florida. Environmentally, dredging of sediments that are rich in CaCO3
      should restore the 19.4-sq km LP by removing natural sediments from the lake
      bottom to improve the fishery, water quality, and navigation of the lake. The
      bottom sediment materials from lakes, river, and navigational channels usually
      are composed of upland soil enriched with nutrients and organic matter. These
      materials should be regarded as a beneficial resource to be used productively and
      not to be discarded as spoil materials. RECOMMENDATION AND OUTLOOK: Land
      application of LDM from LP may not only provide substantial benefits that will
      enhance the environment, community, and society in south Florida, but also in
      other parts of the world especially those areas having tropical and subtropical
      climate with forage-based beef cattle pastures. The heavy and trace metal
      contents of LDM from LP were below the PEL and TEL. As such, the agricultural or
      livestock industry could utilize these LDM to produce forages (Part 2 of this
      study). LDM should be regarded as a beneficial resource, as a part of the
      ecological system. Further studies are still needed to determine whether the
      environmental and ecological implications of LDM application are satisfied over
      the longer term.

PMID- 15506636
TI  - Toxicity of tributyltin to willow trees.
AB  - BACKGROUND: Tributyltin is an organotin compound, used as an antifouling agent in
      ship paint, with heavy impact on the marine environment. Contaminated dredged
      harbor sludge is now dumped on land. The toxicity of tributyltin (TBT) to trees
      has not yet been quantified. Eventually, a vegetation cover on the dumped sludge
      could be established for the purpose of non-food cash crop production and
      phytoremediation. METHODS: The phytotoxicity of tributyltin chloride (TBTCl) and
      tributyltin hydride (TBTH) was measured at pH 4 and at pH 7 using the willow tree
      transpiration test. Different pH levels of the nutrient solutions were achieved
      by adding ammonium salt (low pH) or nitrate (high pH) as nitrogen source. RESULTS
      AND DISCUSSION: At low pH (pH 4), all trees showed symptoms of poor health.
      Transpiration decreased at concentrations above or equal to 0.1 mg TBTCl/l and 1
      mg TBTH/L. The TBT toxicity was more pronounced at pH 7. The trees survived even
      the highest dose of 10 mg/l TBTCl or TBTH, although their growth and
      transpiration was strongly reduced. CONCLUSION: In contrast to other organisms,
      TBTCl and TBTH were less toxic to higher plants. RECOMMENDATIONS AND OUTLOOK: The
      toxicity of TBT is no hindrance for establishing vegetation on TBT-contaminated
      sludge. Phytoremediation and cash crop production could be possible with suitable
      plants.

PMID- 15506637
TI  - Dendroremediation of trinitrotoluene (TNT). Part 2: fate of radio-labelled TNT in
      trees.
AB  - BACKGROUND, AIM AND SCOPE: Problems of long-term existence of the environmental
      contaminant 2,4,6-trinitrotoluene (TNT) and necessities for the use of trees
      ('dendroremediation') in sustainable phytoremediation strategies for TNT are
      described in the first part of this paper. Aims of the second part are estimation
      of [14C]-TNT uptake, localisation of TNT-derived radioactivity in mature tree
      tissues, and the determination of the degree of TNT-degradation during
      dendroremediation processes. METHODS: Four-year-old trees of hybrid willow (Salix
      spec., clone EW-20) and of Norway spruce (Picea abies) were cultivated in sand or
      ammunition plant soil (AP-soil) in wick supplied growth vessels. Trees were
      exposed to a single pulse application with water solved [U-14C]-TNT reaching a
      calculated initial concentration of 5.2 mg TNT per kg dry soil. Two months after
      application overall radioactivity and extractability of 14C were determined in
      sand/soil, roots, stem-wood, stem-bark, branches, leaves, needles, and Picea May
      sprouts. Root extracts were analysed by radio TLC. RESULTS: 60 days after [14C]
      TNT application, recovered 14C is accumulated in roots (70% for sand variants,
      34% for AP-soil variant). 15-28% of 14C remained in sand and 61% in AP-soil. 3.3
      to 14.4% of 14C were located in aboveground tree portions. Above-ground
      distribution of 14C differed considerably between the angiosperm Salix and the
      gymnosperm Picea. In Salix, nearly half of above-ground-14C was detected in bark
      free wood, whereas in Picea older needles contained most of the above-ground-14C
      (54-69%). TNT was readily transformed in tree tissue. Approximately 80% of 14C
      was non-extractably bound in roots, stems, wood, and leaves or needles. Only
      quantitatively less important stem-bark of Salix and Picea and May shoots of
      Picea showed higher extraction yields (up to 56%). DISCUSSION: Pulse application
      of [14C]-TNT provided evidence for the first time that after TNT-exposure, in
      tree root extracts, no TNT and none of the known metabolites, mono-amino
      dinitrotoluenes (ADNT), diaminonitrotoluenes (DANT), trinitrobenzene (TNB) and no
      dinitrotoluenes (DNTs) were present. Extractable portions of 14C were small and
      contained at least three unknown metabolites (or groups) for Salix. In Picea,
      four extractable metabolites (or groups) were detected, where only one metabolite
      (or group) seemed to be identical for Salix and Picea. All unknown extractables
      were of a very polar nature. CONCLUSIONS: Results of complete TNT-transformation
      in trees explain some of our previous findings with 'cold analytics', where no
      TNT and no ADNT-metabolites could be found in tissues of TNT-exposed Salix and
      Populus clones. It is concluded that 'cold' tissue analysis of tree organs is not
      suited for quantitative success control of phytoremediation in situ.
      RECOMMENDATIONS AND OUTLOOK: Both short rotation Salicaceae trees and conifer
      forests possess a dendroremediation potential for TNT polluted soils. The
      degradation capacity and the large biomass of adult forest trees with their woody
      compartments of roots and stems may be utilized for detoxification of soil
      xenobiotics.

PMID- 15506638
TI  - Phytoremediation of petroleum hydrocarbons in tropical coastal soils. II.
      Microbial response to plant roots and contaminant.
AB  - GOAL, SCOPE AND BACKGROUND: The goal of this study was to understand the
      interaction between plants and microorganisms during petroleum-hydrocarbon
      bioremediation in Pacific Islands coastal soils. Total bacteria and hydrocarbon
      degrading microorganisms population dyanamics were examined in the rhizospheres
      of tropical trees and shrubs, which were evaluated for their phytoremediation
      potential in a greenhouse experiment. The respective and combined effects of
      plant roots and diesel contaminant on the microbial populations were determined
      in relation to diesel fuel depletion. An increase in the grading populations size
      of the hydrocarbon-degrading populations of microbes, elicited by
      rhizodeposition, is generally regarded as conducive to an enhanced degradation of
      petroleum hydrocarbon pollutants in vegetated soil. METHODS: The soil was a
      coastal sandy loam (pH 7.8) which was artificially contaminated with 10 g of No.
      2 diesel fuel/kg soil or left uncontaminated. The pots were irrigated with
      fertilizer and 1% NaCl. The enumerations were carried out in the contaminated and
      uncontaminated rhizospheres of three trees, kiawe (Prosopis pallida), milo
      (Thespesia populnea), and kou (Cordia subcordata) and three shrubs, beach naupaka
      (Scaevola sericea), false sandalwood (Myoporum sandwicense), and oleander (Nerium
      oleander). Unplanted control soils were included in the experiment. Total
      bacteria and phenanthrene-degrading bacteria were enumerated on plates. Diesel-
      and pristane-degrading microorganisms were enumerated by the most-probable-number
      technique in tissue-culture plates. RESULTS AND DISCUSSION: All four types of
      microorganisms responded to the rhizosphere of the 6 plants in uncontaminated
      soil and to the diesel contaminant in unplanted soil. In contaminated
      rhizospheres, no effect of the plant on the hydrocarbon-degrader numbers was
      visible. Total bacteria responded more to the plant roots than to the
      contaminant. The phenanthrene-degrading bacteria and pristane-degrading
      microorganisms were more influenced by the contaminant than by the plants. The
      diesel-degrading microorganisms were equally stimulated by the plants and the
      contaminant. The numbers of hydrocarbon degraders were similar in the
      contaminated rhizospheres of the three effective plants (kiawe, kou, and milo)
      and in those of the three ineffective shrubs. CONCLUSION: The results suggest the
      quality of the rhizodeposition is plant-dependent and governs the type of diesel
      degrader populations that will be enhanced by a given plant. RECOMMENDATIONS AND
      OUTLOOK: In the proposed phytoremediation-benefit model plant roots maintain high
      levels of hydrocaron degraders in uncontaminated soil. When the root enters a
      contaminated zone of soil, those hydrocarbon degraders that prefer the
      contaminant would switch to the contaminant as a carbon source, effectively
      removing the hydrocarbons. If the root exudates and the contaminant are equally
      attractive to the hydrocarbon degraders, the contaminant degradaton would be less
      effective.

PMID- 15506639
TI  - Inhibitory role of transcription factor COUP-TFII in expression of hTERT in HeLa
      cells.
AB  - OBJECTIVE: To clone and identify the proteins involved in regulating the
      transcription of hTERT and study the role of genes in both hTERT transcription
      and telomerase activity. METHODS: The full cDNA of COUP-TFII was cloned from HeLa
      cDNA library by hTERT promoter-based yeast one-hybrid assay and then in-frame
      inserted into His-tag fusion expression vector pEK318. The His-tag COUP-TFII
      fusion proteins were purified by Ni-NTA chromatography. The interaction of COUP
      TFII with hTERT promoter in vitro was identified by electrophoretic mobility
      shift assay and Footprint. The role of COUP-TFII in both hTERT transcription and
      telomerase activity were probed through Luciferase reporter assay, Northern blot,
      and TRAP-PCR ELISA. RESULTS: COUP-TFII could firmly bind to the downstream E-box
      and the other two binding sites in hTERT promoter. Luciferase reporter assay
      indicated COUP-TFII could suppress hTERT promoter activity and stable
      introduction of COUP-TFII into HeLa cells also decreased both endogenous hTERT
      transcription and telomerase activity. CONCLUSION: The human COUP-TFII can firmly
      bind to hTERT promoter, and inhibit telomerase activity through decreasing hTERT
      transcription. It will greatly facilitate understanding of telomerase regulation
      in normal and cancer cells.

PMID- 15506640
TI  - Beta2-adrenergic receptor gene polymorphism in Chinese Northern asthmatics.
AB  - OBJECTIVE: To investigate whether the polymorphisms of beta2-adrenergic receptor
      (beta2-AR) at position 16, 27, 164 are associated with asthma in Northern Chinese
      subjects. METHODS: Genomic DNA was collected from unrelated Northern Chinese
      population of Han ethnicity, including 125 unrelated asthmatic individuals and 96
      healthy controls. Beta2-AR genes at position 16, 27, 164 were amplified by using
      restriction fragment length polymorphism (RFLP) and allelic specific polymerase
      chain reaction methods. All asthmatics had their serum IgE (total and specific)
      antibody or skin-prick test measured, bronchial reactivity to methacholine (Mch)
      and bronchial reversibility by beta2-agonist evaluated. RESULTS: (1) The
      frequency of Gly 16 homozygous was significantly higher in the asthmatic group
      than that in healthy controls (22.4% vs. 8.3%, P < 0.05), OR was 2.9 with 95% CI
      1.26-6.78. The proportion of Gly 16 allele was also higher in asthmatics than
      that in control (0.46 vs. 0.36, P < 0.05); Gly16 homozygous was not independently
      associated with asthma pathogenesis (P = 0.21, OR 0.42 with 95% CI 0.11-1.61).
      (2) Of 51 night attack patients, 18 carrying Gly16 homozygosity, if compared with
      10 of 74 nonnocturnal asthmatics carrying this genotype, there was significant
      difference between these two groups (35.3% vs. 13.5%, P < 0.01). (3) The average
      dose of PD20-Mch was significantly lower in patients carrying Gln 27 homozygous
      than those carrying homozygous Glu 27 and Gln/Glu 27 heterozygous (0.2 +/- 0.3,
      1.6 +/- 0.8, and 2.1 +/- 3.0 micromol/L, P < 0.05). CONCLUSION: Beta2AR gene
      polymorphisms might confer susceptibility to asthma in Chinese Northern patients.
      Beta2-AR gene, coordinated with other candidate loci, plays a role in the
      development of asthma.

PMID- 15506641
TI  - Expression of mRNA for membrane-type 1, 2, and 3 matrix metalloproteinases in
      human laryngeal cancer.
AB  - OBJECTIVE: To investigate correlation of expressions of membrane-type 1, 2, and 3
      matrix metalloproteinases (MT1, MT2, and MT3-MMP) to the invasion and metastases
      in laryngeal cancer. METHODS: Reverse transcription-polymerase chain reaction (RT
      PCR) was used to examine the mRNA level of MT1, MT2, and MT3-MMP in 24 patients
      with laryngeal cancer. The relationships of these three MT-MMP expressions to
      clinicopathology were analyzed by statistics. RESULTS: The expressions of MT1,
      MT2, and MT3-MMP were significantly higher in laryngeal cancer tissues than those
      in para-tumorous tissues (P < 0.01) and had a close relationship with invasive
      depth (P < 0.05). But no significantly different expressions of these three MT
      MMPs were found in different primary location and different histological grade of
      laryngeal cancer (P > 0.05). The expression of MT1-MMP was obviously higher in
      patients with metastatic lymph nodes than that in patients without metastatic
      lymph nodes (P < 0.05). CONCLUSION: MT1, MT2, and MT3-MMP play an important role
      in the progression of laryngeal cancer, and MT1-MMP may serve as a reliable
      marker in estimating invasive and metastatic potency of laryngeal cancer.
      Suppressing expressions of MT1, MT2, and MT3-MMP early may inhibit the invasion
      and metastases of laryngeal cancer.

PMID- 15506642
TI  - Non-invasive imaging of coronary artery with 16-slice spiral computed tomography.
AB  - OBJECTIVE: To evaluate the value of 16-slice spiral CT in the demonstration of
      coronary artery and in the diagnose of coronary artery stenosis. METHODS: Plain
      and enhanced CT scans were performed with a 16-slice CT scanner (Sensation 16,
      Siemens, Germany) in 230 patients with suspected coronary heart disease (CHD).
      Parameters of the plain scan were: 120 kV, 133 mA, slice collimation 16 mm x 1.5
      mm, rotation time 0.42 seconds, increment 1.5 mm, and slice width 3 mm.
      Parameters of the enhanced scan were: 120 kV, 500 mA, slice collimation 16 mm x
      0.75 mm, rotation time 0.42 seconds, increment 0.5 mm, and slice width 1 mm.
      Enhanced CT scan was performed with a rapid intravenous injection of 100 mL
      iothalamate meglumine (Ultravist) (370 mgI/mL) or Omnipaque (350 mgI/mL) and 30
      mL 0.9% NaCl chaser bolus at a flow rate of 3.5 mL/s. Calcium scoring with plain
      scan images and two and three dimensional reconstruction with enhanced scan
      images were made in all cases, among which 30 cases underwent conventional
      coronary angiography. Demonstration of coronary arteries and their stenosis were
      evaluated and the factors that might influence the image quality were analyzed.
      RESULTS: Coronary calcium scores were calculated and coronary artery was
      demonstrated in our study. In the evaluation of image quality with volume
      rendering technique (VRT) images, 78.3% of the images were of the first class,
      12.2% the second class, and 9.6% the third class. Multi-planar reconstruction
      (MPR) and maximal intensity projection (MIP) were better than VRT in the
      demonstration of small branches. The image quality was related to the heart rate,
      with or without arrhythmia, and breath-hold ability of patients. Comparative
      study of the stenosis of coronary arteries in 30 cases showed that the
      sensitivity and specificity of 16-slice coronary CT angiography (CTA) to diagnose
      significant stenosis were 95.8% and 94.8% respectively. CONCLUSION: As a non
      invasive and quick method, 16-slice coronary CTA is sensitive and specific to
      diagnose the stenosis of coronary arteries and can be used as a screening method
      in the diagnosis of CHD.

PMID- 15506643
TI  - Protective effect of tetramethylpyrazine on learning and memory function in D
      galactose-lesioned mice.
AB  - OBJECTIVE: To explore the protective effect of tetramethylpyrazine (TMP) on the
      learning and memory function in D-galactose (D-gal)-lesioned mice. METHODS:
      C57BL/6 mice were injected (s.c.) 2% D-gal for 40 days (100 mg x kg(-1) x d(-1)).
      Normal saline, TMP, and Huperzine A were respectively given by intragastric
      administration in different groups from the third week. Learning and memory
      ability was tested with Morris water maze for 5 days at the sixth week. After
      completion of behavioral test, the mice were sacrificed by decapitation. The
      brain was rapidly removed, and the cortex and hippocampus were separated. The
      superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in the
      cortex were determined. At the same time, the activity of choline
      acetyltransferase (ChAT) and acetylcholinesterase (AChE), the binding sites
      (Bmax) and the affinity (KD) of M-cholinergic receptor in the cortex, and Bmax
      and KD of N-methyl-D-aspartate (NMDA) receptor in the hippocampus were
      determined. RESULTS: In this model group, (1) The deficit of learning and memory
      ability, (2) elevated MDA content and lowered SOD activity, (3) decreased AChE
      activity and M-cholinergic receptor binding sites in the cortex, and (4) lowered
      NMDA receptor binding sites were observed in the hippocampus, as compared with
      the normal control. TMP could markedly (1) attenuate cognitive dysfunction, (2)
      lower MDA content and elevate SOD activity, (3) increase the activity of ChAT and
      AChE, and M-cholinergic receptor binding sites in the cortex in the mice treated
      with D-gal. NMDA receptor binding sites were also increased in the hippocampus in
      the treated mice. CONCLUSION: TMP can significantly strengthen antioxidative
      function, improve central cholinergic system function, protect NMDA receptor
      activity, and thus enhance the learning and memory ability in D-gal-lesioned
      mice.

PMID- 15506644
TI  - House dust mite allergen (Derp1 and Blot5) levels in asthmatics' home in
      Hongkong.
AB  - OBJECTIVE: To measure Derp1 and Blot5 allergen levels in asthmatics' homes in
      Hongkong. METHODS: Seventy houses were enrolled for a mite indoor environment
      study. Dust samples were obtained from two sites of each patients' house: bed and
      floor. Derp1 and Blot5 levels were quantified by a two-site monoclonal antibody
      based ELISA technique. RESULTS: The levels of Derp1 allergens found in bed
      (geometric mean (GM) 3.43 microg/g of dust; 95%CI, 1.89-4.96 microg/g) and on the
      floor (GM 1.12 microg/g of dust; 95%CI, 0.71-1.53 microg/g) indicated significant
      differences (P=0.005). However, the levels of Blot5 allergens found in bed (GM
      19.00 microg/g of dust; 95%CI, 0.89-38.90 microg/g) and on the floor (GM 6.14
      microg/g of dust; 95%CI, 0.40-11.90 microg/g) showed no statistically significant
      difference. In addition, in regards to the exposure index for Derp1 and Blot5
      allergens found in bed and on the floor, 17.6% in bed and 8.6% on the floor had
      levels of Blot5 > or = 10 microg/g of dust, higher than those obtained for Derp1
      (7.2% and 0% in bed and on the floor respectively, P<0.05); higher percentages in
      bed and on the floor (25.0% and 35.7%) were observed for levels of Blot5 = 0
      microg/g of dust as compared with Derp1 in bed and on the floor (4.3% and 14.5%
      respectively, P<0.05). CONCLUSIONS: Derp1 and Blot5 are the major allergens found
      in this regional study, Blot5 is a more potent allergen in Hongkong, probably
      reflecting the high level of exposure to Blomia tropicalis (Bt). Bt and
      Dermatophagoides pteronyssinus (Dp) allergens should be included for precise
      diagnosis and effective immuno-therapeutic treatment of mite allergy in Hongkong.

PMID- 15506645
TI  - Effects of early nutrition intervention on IGF1, IGFBP3, intestinal development,
      and catch-up growth of intrauterine growth retardation rats.
AB  - OBJECTIVE: To investigate the effects of early nutritional intervention on the
      serum insulin-like growth factor-1 (IGF1), insulin-like growth factor binding
      protein 3 (IGFBP3), intestinal development, and catch-up growth of intrauterine
      growth retardation (IUGR) rats by giving the IUGR new born rats different protein
      level diet. METHODS: IUGR rat model was built by starvation of pregnant female
      rats. Twenty-four IUGR pups and 8 normal pups were divided randomly into 4
      groups: normal control group (C group); IUGR control group (S group), IUGR low
      protein diet group (SL group), and IUGR high-protein diet group (SH group).
      Detected the serum IGF1, IGFBP3, body weight, body length, intestinal weight
      length, intestinal villi height (VH), crypt depth (CD), villi absorbing area
      (VSA), mucous thickness (MT), and disaccharidase at the 4th week. RESULTS: (1)
      The SH group showed the fastest catch-up growth, serum IGF1, IGFBP3, VH, and VSA
      were significantly higher than those of normal control group and IUGR control
      group. The intestinal weight and length, and the activities of lactase and
      saccharase of the SH group also reached the normal control group level. (2) The
      SL group kept on small size, the serum IGF1, IGFBP3, and most of intestinal
      histological indexes were all significantly lower than other groups. (3) IGF1,
      IGFBP3 were positively correlated to intestinal VH, VSA, saccharase, body weight
      and length. CONCLUSIONS: The serum IGF1 was a sensitive index to the catch-up
      growth. The early nutritional intervention of high-protein diet after birth is
      helpful for the catch-up growth of IUGR through promoting the intestinal
      development and the absorption of nutrition.

PMID- 15506646
TI  - Expression of maspin and kai1 and their clinicopathological significance in
      carcinogenesis and progression of gastric cancer.
AB  - OBJECTIVE: To investigate the roles of maspin and kai1 expression in
      tumorigenesis and progression of gastric cancer. METHODS: Maspin and kai1
      expressions were detected in normal gastric mucosa (n = 182), gastric dysplasia
      (n = 69), and gastric cancer (n = 113) by immunohisto-chemistry. Their
      expressions were compared with clinicopathological parameters of tumors.
      Relationship between maspin and kai1 expression was also concerned in gastric
      cancer. RESULTS: The positive rates of maspin expression were 79.8% (145/182),
      75.4% (52/69), and 50.4% (57/113) in normal gastric mucosa, gastric dysplasia,
      and gastric cancer, while those of kai1 expression were 81.9% (149/182), 65.2%
      (49/69), and 58.4% (66/113) in corresponding tissues respectively. Gastric cancer
      less frequently expressed maspin than the normal gastric mucosa and gastric
      dysplasia (P < 0.05), while dysplasia and cancer showed less frequent expression
      of kai1 than normal mucosa (P < 0.05). Maspin expression showed negative
      association with invasive depth, metastasis, Lauren's and histological
      classifications (P < 0.05), but not with tumor size, Borrmann's classification,
      growth pattern or TNM staging (P > 0.05). Kai1 expression was negatively
      correlated with invasive depth, metastasis, growth pattern, Lauren's and
      histological classifications (P < 0.05), but not with tumor size, Borrmann's
      classification or TNM staging (P > 0.05). Maspin and kai1 were collaboratively
      expressed in gastric cancer (P < 0.05). CONCLUSIONS: Down-regulated expressions
      of maspin and kai1 play an important role in gastric carcinogenesis. Abnormal
      expression of maspin and kai1 might have inhibitory effects on invasion and
      metastasis of gastric cancer and act as an effective and objective marker to
      indicate the pathobiological behaviors of gastric cancer.

PMID- 15506647
TI  - Single cell HLA matching feasibility by whole genomic amplification and nested
      PCR.

PMID- 15506648
TI  - Elevated soluble epidermal growth factor receptor level in pituitary adenoma and
      carcinoma.
AB  - OBJECTIVE: To investigate effect of the soluble epidermal growth factor receptor
      (sEGFR/sErbB1) level in the peripheral blood in development, invasiveness,
      apoplexy of each type of pituitary tumor. METHODS: The sEGFR level was determined
      in peripheral serum from 190 patients with pituitary diseases by enzyme linked
      immunosorbent assay. The sEGFR levels were measured in 10 pituitary Rathke's
      pouch, 18 pituitary hyperplasia, 161 pituitary adenomas including 30
      microadenomas, 83 large adenomas, 48 giant adenomas, 1 pituitary carcinoma, and
      28 healthy controls. RESULTS: In the patients with pituitary hyperplasia,
      microadenoma, large adenoma, giant adenoma, and pituitary carcinoma, the sEGFR
      level was 188.92 +/- 32.62, 209.83 +/- 19.01, 333.20 +/- 69.33, 405.85 +/- 37.38,
      and 617.45 fmol/mL independently. They were all significantly higher than
      patients with pituitary Rathke's pouch (156.78 +/- 18.24 fmol/mL, P < 0.001) and
      healthy control group (159.11 +/- 40.50 fmol/mL, P < 0.05). The sEGFR level in
      pituitary carcinoma was higher than pituitary adenoma. In patients with pituitary
      adenoma, the sEGFR level was positive correlated to the size of pituitary
      adenomas (r=0.998), the significant difference was observed for the sEGFR level
      in each group of the patients with pituitary adenomas (P < 0.001). Furthermore,
      in patients with pituitary ACTH-secreting microadenomas, the serum sEGFR levels
      in invasiveness (295.00 +/- 77.80 fmol/mL) was higher than that in non
      invasiveness (210.60 +/- 16.4 fmol/mL, P < 0.05). In patients with pituitary ACTH
      secreting, PRL-secreting, GH-secreting, and non-functioning large adenomas, the
      serum sEGFR levels in invasiveness (407.86 +/- 28.50, 399.25 +/- 30.10, 386.00 +/
      13.08, and 369.25 +/- 36.70 fmol/mL) was higher than that in non-invasiveness
      (335.25 +/- 63.49, 300.64 +/- 47.57, 297.00 +/- 61.93, and 269.30 +/- 25.68
      fmol/mL) respectively (P < 0.05). In patients with invasive pituitary PRL
      secreting, GH-secreting, and non-functioning giant adenomas, the serum sEGFR
      levels not significantly different in between invasiveness (417.50 +/- 35.94,
      409.50 +/- 69.14, and 417.50 +/- 44.13 fmol/mL) and non-invasiveness (386.00 +/-
      49.64, 417.50 +/- 44.03, and 409.51 +/- 35.17 fmol/mL) (P > 0.05). In patients
      with pituitary large adenomas, the sEGFR levels in pituitary apoplexy (377.48 +/-
      39.18 fmol/mL) was higher than that in non-pituitary apoplexy (343.18 +/- 68.17
      fmol/mL, P > 0.05). CONCLUSIONS: The increased level of peripheral serum sEGFR is
      concomitant with development, proliferous size of the adenomas in patients with
      pituitary adenomas. In addition, the elevated levels of serum sEGFR occur in
      pituitary apoplexy as clinical active tumors, and the non-invasive ACTH secreting
      adenomas. The sEGFR levels could be differentiated helpfully between pituitary
      adenomas and non-pituitary adenomas. These data suggest that serum sEGFR could be
      as a referable marker of the size and activation of proliferation in pituitary
      adenoma.

PMID- 15506649
TI  - Assessment of diastolic function in patients with hypertrophic cardiomyopathy by
      Doppler tissue imaging.
AB  - OBJECTIVE: To determine the clinical application of pulsed Doppler tissue imaging
      in assessing the left ventricular diastolic function and in discriminating
      between normal subjects and patients with hypertrophic cardiomyopathy with
      various stages of diastolic dysfunction. METHODS: We measured the peak diastolic
      velocities of mitral annulus in 81 patients with hypertrophic cardiomyopathy with
      various stages of diastolic dysfunction and 50 normal volunteers by Doppler
      tissue imaging using the apical window at 2-chamber and long apical views,
      respectively. The myocardial velocities were determined with use of variance F
      statistical analysis. RESULTS: Early diastolic myocardial velocities of mitral
      annulus were higher in normal subjects than in patients with hypertrophic
      cardiomyopathy with either delayed relaxation, pseudonormal filling, or
      restrictive filling. However, peak myocardial velocities of mitral annulus during
      atrial contraction were similar in normal subjects and patients with hypertrophic
      cardiomyopathy. CONCLUSION: Doppler tissue imaging can directly reflect upon left
      diastolic ventricular function. Early phase of diastole was the best
      discriminator between control subjects and patients with hypertrophic
      cardiomyopathy.

PMID- 15506650
TI  - Expression of human beta-defensin 3 in COS-7 cell.
AB  - OBJECTIVE: To establish a cell line for stable expression of human beta-defensin
      3 (hBD3). METHODS: Full length cDNA of hBD3 was isolated from previously
      constructed pGEM-hBD3 and then inserted into pcDNA3. The recombinant vector
      identified carrying hBD3 with right direction was introduced into COS-7 cells by
      Lipofectamine. Cell clones survived in G418-rich medium and with stable
      expression of hBD3 in both mRNA and protein levels were identified by RT-PCR and
      Western blot respectively. Genomic integration of the hBD3 gene with the COS-7
      cells was confirmed by Southern dot blot and primary analysis. The antimicrobial
      activity of the secreted hBD3 was also evaluated. RESULTS: COS-7 cells
      transfected with pcDNA3-hBD3 expressed hBD3 stably in mRNA and protein level.
      Southern dot blot analysis showed successful integration of the hBD3 gene into
      the genome of COS-7 cell and the hBD-3 protein secreted into the culture medium
      showed antimicrobial activity. CONCLUSION: We successfully established a hBD3
      expressing cell line.

PMID- 15506651
TI  - Correlation between serum HER-2 oncoprotein and patients with breast cancer.
AB  - OBJECTIVE: To detect serum HER-2 oncoprotein levels in patients with operable and
      metastatic breast cancers, and to study the correlations between serum HER-2
      level and lymph node status as well as other clinical parameters. METHODS: A
      total of 120 women were studied consisting of 10 healthy volunteers, 31 benign
      breast disease, 53 operable breast cancer, and 26 metastatic breast cancer
      patients. The levels of serum HER-2 were measured using an enzyme-liked
      immunosorbent assay (ELISA). RESULTS: The mean serum HER-2 levels were 9.6 +/-
      1.5 ng/mL in healthy volunteers, 11.9 +/- 1.6 ng/mL in benign breast disease,
      13.2 +/- 4.2 ng/mL in operable breast cancer, and 30.5 +/- 30.8 ng/mL in
      metastatic breast cancer patients. The former is much lower than the latter three
      (P = 0.02, 0.001, 0.03, respectively). If using 15 ng/mL as a normal baseline,
      elevated serum HER-2 levels were observed in none of the healthy volunteers as
      well as patients with benign disease, but in 18.9% (10/53) operable breast cancer
      patients and 61.5% (16/26) metastatic patients. In patients with operable breast
      cancer, there was a positive correlation between serum concentrations of HER-2
      and the size of primary tumor (P < 0.05), whereas there was no correlation
      between serum concentration and axillary lymph node or estrogen receptor status.
      In patients with metastatic disease, there was no correlation with site of
      metastases (P > 0.05). CONCLUSION: Serum HER-2 level was strongly correlated with
      tumor loads and clinical stages, thus acting as a promising predictor of cancer
      recurrence in breast cancer patients.

PMID- 15506652
TI  - Posterior selective thoracic fusion in adolescent idiopathic scoliosis.
AB  - OBJECTIVE: To define the criteria of posterior selective thoracic fusion in
      patients with adolescent idiopathic scoliosis. METHODS: By reviewing the medical
      records and roentgenograms of 17 patients with adolescent idiopathic scoliosis
      who underwent posterior selective thoracic fusion, the curve type, Cobb angle,
      apical vertebral rotation and translation, trunk shift, and thoracolumbar
      kyphosis were measured and analyzed. RESULTS: There were 17 King type II patients
      (PUMC type: IIb, 13, IIc3 4). The coronal Cobb angle of thoracic curve before and
      after operation were 56.9 degrees and 21.6 degrees respectively, the mean
      correction rate was 60.1%. The coronal Cobb angle of lumbar curve before and
      after operation were 34.8 degrees and 12.1 degrees respectively, and the mean
      spontaneous correction rate was 64.8%. At final follow-up, the coronal Cobb angle
      of thoracic and lumbar curve were 23.5 degrees and 15.2 degrees respectively,
      there were no significant changes in the coronal Cobb angle, apical vertebral
      translation and rotation compared with that after operation. One patient had 12
      degrees of thoracolumbar kyphosis after operation, no progression was noted at
      final follow-up. There was no trunk decompensation or deterioration of the lumbar
      curve. In this group, 3.9 levels were saved compared with fusing both the
      thoracic and lumbar curves. CONCLUSION: Posterior selective thoracic fusion can
      be safely and effectively performed in King type II patients with a moderate and
      flexible lumbar curve, which can save more mobile segments and at the same time
      can maintain a good coronal and sagittal balance.

PMID- 15506653
TI  - Expression and subcellular localization of P9-ZFD protein in patients with
      myasthenia gravis.
AB  - OBJECTIVE: To express and purify the protein coded by the TRAF-type zinc finger
      domain of myasthenia gravis (MG)-related gene P9 (P9-ZFD) and to prepare P9-ZFD
      antiserum for detecting expression and subcellular distribution of P9-ZFD protein
      in the skeletal muscles of patient with MG. METHODS: The cDNA encoding P9-ZFD was
      amplified by RT-PCR. The cloned P9-ZFD cDNA was ligated into pET24a, and the P9
      ZFD recombinant protein was induced via E. coli. BL21 (DE3) and purified by
      histidine affinity chromatography. P9-ZFD antiserum was prepared and its titer
      and specificity were determined by ELISA and Western blot. Expression and
      subcellular distribution of P9-ZFD protein in the skeletal muscles of MG and
      control were studied. RESULTS: The molecular weight of purified P9-ZFD protein
      was about 30 kD. Its purity was more than 95%. Antiserum specific for P9-ZFD was
      excellent. P9-ZFD protein is fully confined to the cytoplasm membrane of skeletal
      muscle cell of MG, obvious immunostaining was absent in the A, I, and Z bands of
      cytoplasm and no immunoreactivity was observed in the skeletal muscle cell of
      control. CONCLUSION: P9-ZFD protein is expressed as a cytoplasm membrane-bound
      protein and has obvious distribution difference in the skeletal muscle cells of
      patient with MG and normal control.

PMID- 15506655
TI  - Real-time three-dimensional echocardiography for quantifying left ventricular
      mass.
AB  - OBJECTIVE: To test the accuracy of real-time three-dimensional echocardiography
      (RT3DE) imaging system for evaluating left ventricular mass (LVM) in phantom and
      excised canine heart. METHODS: Ten left ventricular (LV) wall phantoms made of
      two rubber-bursas, ten excised canine hearts underwent RT3DE and two-dimensional
      echocardiography (2DE). In RT3DE "full volume" imaging, the myocardial volume was
      measured using 2, 4, 8, and 16-plane method with the analysis software of RT3DE.
      Mass was then calculated by multiplying the resulting myocardial volume by
      specific density of myocardial tissue. In 2DE the masses were measured by area
      length method. The true LV wall phantom mass was measured by water displacement
      and the canine LVM was weighed by anatomy, which served as a reference standard.
      We compared RT3DE or 2DE with true mass. RESULTS: In LV wall phantoms, RT3DE
      correlated with true masses strongly (r = 0.813-0.994) and weakly correlated
      between 2DE and true masses (r = 0.628). In excised canine hearts, there is an
      excellent correlation between RT3DE and true masses (r = 0.764-0.991), while 2DE
      value showed a lesser correlation (r = 0.514). There are no difference between RT
      3DE and true masses (P > 0.05) but different between 2DE and true masses (P <
      0.05). In different planes, there was no difference between 8-plane and 16-plane
      (P > 0.05) but different between 8-plane and 2, 4-plane (P < 0.05). CONCLUSION:
      RT3DE can accurately quantify LVM and provide a new tool to evaluate LV function.
      For LVM by RT3DE, 8-plane measurement method is the best choice for accuracy and
      convenience.

PMID- 15506654
TI  - Effects of China-made recombinant human growth hormone on the treatment of growth
      hormone deficiency.
AB  - OBJECTIVE: To evaluate the therapeutic effect of China-made recombinant human
      growth hormone (r-hGH) in children with growth hormone deficiency (GHD) and to
      investigate the utilities of various biochemical parameters in GHD diagnosis and
      treatment. METHODS: Our study comprises of 30 normal children and 71 GHD children
      treated with China-made r-hGH substitution therapy 0.1 IU x kg(-1) x d(-1) for 6
      months. Serum insulin-like growth factor-1 (IGF-1), insulin-like growth factor
      binding protein 3 (IGFBP-3), bone turnover markers (Ost, ICTP), and anti-growth
      hormone antibody (GHAb) were detected before and after r-hGH treatment. RESULTS:
      After the first 3 and 6 months of treatment, growth velocities of GHD children
      were significantly increased (13.1 +/- 3.7 and 12.6 +/- 3.6 cm/year) compared
      with pretreatment values (2.9 +/- 0.8 cm/year, P < 0.01). GHD Children had
      obviously reduced serum levels of IGF-1, IGFBP-3, and bone turnover markers (Ost,
      ICTP) compared with normal controls (P < 0.01), and these biochemical parameters
      improved significantly after treatment (P < 0.01). Growth hormone antibodies were
      positive in 17 of 45 cases after treatment by binding capacity detection. The
      binding percentage of growth hormone antibody which was increased more than 30%
      after the treatment showed a negative correlation with growth velocity (P <
      0.01). CONCLUSIONS: (1) The growth stimulating effect and safety were confirmed
      in using China-made r-hGH in the treatment of GHD children for 6 months. (2) The
      measurements of serum IGF-1 and IGFBP-3 may serve as useful parameters in the
      diagnosis of GHD. (3) Serum Ost and ICTP are useful laboratory criteria for
      evaluating the effect of r-hGH therapy in the early stage. (4) It is necessary to
      monitor serum levels of GHAb during r-hGH therapy.

PMID- 15506656
TI  - Construction and immunogenicity of human papillomavirus type 6b L1 recombinant
      plasmid.
AB  - OBJECTIVE: To construct a DNA vaccine as a prophylactic model to prevent
      condyloma acuminatum and detect its immunogenicity in mice. METHODS: The major
      capsid protein (L1) gene of human papillomavirus (HPV) 6b was inserted into an
      eukaryotic expression plasmid (pcDNA3.1). The recombinant plasmid was transfected
      into COS-7 cells. Western blot were performed to detect whether L1 protein can be
      expressed in eukaryotic cells. Eighteen female BALB/c mice were tested for
      immunogenicity study. RESULTS: The recombinant plasmid (pcDNA3.1-HPV6bL1) was
      verified as HPV6b L1 gene by sequencing. Western blot showed specific strip. Anti
      L1 protein antibodies could be detected in the mice's sera inoculated with
      pcDNA3.1-HPV6bL1. Similarly, IL-4, IL-2, and IFN-gamma were increased in the same
      mice. CONCLUSION: HPV6b L1 recombinant plasmid was constructed successfully which
      had immunogenicity for BALB/c mice. It provided experimental evidence for the
      research of DNA vaccine of condyloma acuminata.

PMID- 15506657
TI  - Real-time three-dimensional echocardiography in assessment of left ventricular
      and right ventricular volumes.

PMID- 15506658
TI  - Binocular vision function analysis of 75 subjects.

PMID- 15506659
TI  - The power of no.

PMID- 15506660
TI  - Should smokers be considered a high-risk group for colorectal cancer?

PMID- 15506661
TI  - Natural history of initially mild chronic hepatitis C.
AB  - The hepatitis C virus is a leading cause of chronic liver disease, cirrhosis and
      hepatocellular carcinoma in western countries. Chronic hepatitis C is highly
      heterogeneous and many patients present with a mild form of liver disease.
      Population-based studies have indeed demonstrated that around 50% of hepatitis C
      virus carriers have persistently normal ALT and two-third have mild histological
      liver lesions. Studies on the natural history of initially mild chronic disease
      indicate that the short-term outcome is always benign. However, progression of
      liver fibrosis can be observed at long-term (>5-7 years) follow-up, particularly
      in those cases who have elevated and/or fluctuating transaminase levels.
      Observational prospective studies and outcome modelling projections indicate that
      the risk of liver disease progression towards severe fibrosis/cirrhosis is
      minimal at 10-15 years in hepatitis C virus carriers with persistently normal
      ALT, around 5-10% in patients with elevated ALT and F0 (no fibrosis) in the
      initial biopsy but >30-40% in chronic carriers with elevated ALT and F1 (portal
      fibrosis) in the initial biopsy. Cofactors like age at infection, alcohol,
      coinfections and liver steatosis accelerate disease progression. On the basis of
      these findings, patients with initially mild chronic hepatitis C and elevated ALT
      should be proposed for antiviral therapy in the absence of contraindications.

PMID- 15506662
TI  - Prevention of aspirin-induced gastroduodenal damage: H. pylori infection
      eradication versus proton pump inhibitors or both.

PMID- 15506663
TI  - Screening for coeliac disease antigen source and performance of the anti-tissue
      transglutaminase ELISA.

PMID- 15506664
TI  - Breath sample collection through the nostril reduces false-positive results of
      13C-urea breath test for the diagnosis of helicobacter pylori infection.
AB  - BACKGROUND: One of the disadvantages of '3C-urea breath test is possible
      interference by urease activity not related to Helicobacterpylori. AIMS: We
      design the simple and non-invasive modification to avoid the contamination of
      13CO(2) produced in the mouth. PATIENTS AND METHODS: One hundred and twenty-nine
      patients who underwent diagnostic upper endoscopy were enrolled. Within 1 week of
      the endoscopic procedure, each patient received the modified 13C-urea breath
      test. Breath samples were collected at baseline and at 1, 3, 5, 10, 15, 20 and 30
      min after ingestion of 100 mg 13C-urea solution through the mouth and the nostril
      at each time point. RESULTS: The breath delta13CO2 value through the nostril at 1
      min was already higher in H. pylori-positive patients than in H. pylori-negative
      patients. Using 2.5% as the cut-off value, the sensitivity and specificity of the
      modified 13C-urea breath test at 20 min were both 100%, whereas the sensitivity
      and specificity of the standard 13C-urea breath test were 97.7 and 94%,
      respectively, using 3% as the cut-off value. CONCLUSIONS: The modified 13C-urea
      breath test in which breath samples are collected through the nostril provides an
      easy way of avoiding false-positive results for the detection of H. pylori
      infection.

PMID- 15506665
TI  - Helicobacter pylori infection and the prevention of peptic ulcer with proton pump
      inhibitors in elderly subjects taking low-dose aspirin.
AB  - INTRODUCTION: The role of Helicobacter pylori infection on the risk of low-dose
      aspirin-related gastroduodenal damage and on the efficacy of the prevention
      therapy in elderly chronic users of low-dose aspirin is still controversial. AIM:
      To evaluate in symptomatic elderly chronic users of low-dose aspirin: (1) the
      association between H. pylori infection and the prevalence of upper
      gastrointestinal lesions; and (2) the effect of H. pylori infection on the
      efficacy of proton pump inhibitors in the prevention of aspirin-related
      gastroduodenal lesions. PATIENTS AND METHODS: Two hundred and forty-five
      symptomatic elderly who were taking aspirin 75-300 mg daily, at least during the
      last 3 months, were evaluated by endoscopy. A structured interview was carried
      out to evaluate gastrointestinal symptoms and the use of proton pump inhibitors.
      H. pylori infection was diagnosed according to histology and the rapid urease
      test on gastric biopsies. RESULTS: One hundred and twelve patients were H. pylori
      positive and 133 patients were H. pylori-negative. A significantly higher
      prevalence of peptic ulcers was observed in H. pylori-positive than in H. pylori
      negative subjects (36.6% versus 15.8%, P = 0.0002). The use of proton pump
      inhibitors was associated with a significant decreased risk of peptic ulcer both
      in H. pylori-positive (absolute risk reduction, ARR = -36.2, 95% confidence
      interval: -51.2 to -21.3, P < 0.001) and H. pylori-negative patients (ARR = 
      12.6, 95% confidence interval: -23.9 to -1.2, P = 0.03). However, the number of
      patients who needed to be treated in order to gain a reduction of one peptic
      ulcer (number needed to treat, NnT) was lower in H. pylori-positive than in H.
      pylori-negative patients (NnT = 3 versus 8). CONCLUSIONS: In symptomatic elderly
      chronic users of low-dose aspirin, H. pylori infection may influence the
      prevalence of peptic ulcers and the cost-effectiveness of the proton pump
      inhibitor prevention therapy.

PMID- 15506666
TI  - Anti-human versus anti-guinea pig tissue transglutaminase antibodies as the first
      level serological screening test for coeliac disease in the general population.
AB  - BACKGROUND: So far the reliability of the anti-guinea pig and anti-human tissue
      transglutaminase antibodies for the coeliac disease diagnosis has been evaluated
      in selected groups of patients. AIM: To compare the diagnostic accuracy of anti
      human versus anti-guinea pig tissue transglutaminase in the coeliac disease
      screening of the general population. SUBJECTS: Two healthy Italian populations
      living in Marche region and in Western Sardinia. METHODS: Both anti-guinea pig
      and anti-human tissue transglutaminase were determined using an enzyme-linked
      immunosorbent assay-based commercially available kit (Eu-tTG, Eurospital,
      Trieste, Italy). RESULTS: During the period 1999-2001, 3541 subjects (1500 from
      "continental" Italy and 2041 from Sardinia) were screened for coeliac disease
      using both anti-guinea pig and anti-human tissue transglutaminase as first-level
      tests. Both these tests were negative in 3439/3541 sera, while 29 resulted
      positive for both of them and 73 showed discordant results. Overall, 50
      intestinal biopsies were performed in 22, 21 and 7 subjects with positivity to
      both screening tests, to anti-guinea pig and to anti-human tissue
      transglutaminase alone, respectively. A coeliac disease diagnosis was made in 25
      subjects giving an overall prevalence of 1:126 individuals. The anti-tissue
      transglutaminase specificity and sensitivity were 98 and 92% for guinea pig and
      99.6 and 96% for human tissue transglutaminase, respectively. CONCLUSIONS: The
      anti-human tissue transglutaminase test should definitely replace the anti-guinea
      pig-derived one as first-level screening tool for identifying all subjects who
      need the second-level investigations (small intestinal biopsy).

PMID- 15506667
TI  - Serum lamivudine levels in the presence of a lamivudine-resistant HBV mutant.
AB  - BACKGROUND/AIMS: Lamivudine efficiently inhibits hepatitis B virus replication
      and has been used to treat hepatitis B virus recurrence after orthotopic liver
      transplantation. Although effective, its use is hampered by viral breakthrough
      due to the appearance of hepatitis B virus drug-resistant strains. Aims of this
      work were to evaluate the inter- and intra-individual variations of lamivudine
      serum levels and the effects on the drug levels of the lamivudine-resistant
      hepatitis B virus mutant infection. METHODS: Serum lamivudine concentration was
      measured by high-performance liquid chromatography. Polymerase chain reaction
      analysis and sequencing analysis of the reverse transcriptase area of the
      polymerase was performed on each sample using specific primers. A polymerase
      chain reaction-enzyme-linked immunosorbent assay was used to differentiate
      between wild-type hepatitis B virus and lamivudine-resistant hepatitis B virus
      strain. RESULTS: Lamivudine serum levels presented minor inter- and intra
      individual fluctuations along time, with an important increase at the time of the
      hepatitis flare-up due to the hepatitis B virus mutant presence. When the wild
      type hepatitis B virus briefly reappeared as a mixed population, the titre of
      lamivudine dropped to below the detection level. CONCLUSIONS: While lamivudine
      serum levels appears stable when the anti-viral efficacy is fully achieved,
      important fluctuations are present according to the type of viral population,
      with a considerable decrease possibly due to the presence of the wild-type virus.

PMID- 15506668
TI  - Bethanechol provocation testing does not predict symptom relief after
      cholecystectomy for acalculous biliary pain.
AB  - BACKGROUND: The currently accepted hypothesis to explain acalculous gallbladder
      pain is the lack of contractile co-ordination between the body and neck. We have
      previously shown that bethanechol, a muscarinic stimulant causes differential
      stimulation of these two regions. AIM: To evaluate the reliability of bethanechol
      induced gallbladder contraction in predicting symptom relief after
      cholecystectomy in patients with acalculous gallbladder disease. METHODS: Fifty
      one patients underwent a bethanechol provocation test together with serial
      ultrasound to determine gallbladder emptying. McGill pain questionnaires were
      completed, and patients positive for pain (bethanechol provocation test +ve) were
      offered cholecystectomy, and patients negative for pain (bethanechol provocation
      test -ve) were reassessed at 6 months and offered cholecystectomy if symptoms
      persisted. All patients answered pain questionnaires either 6 months after
      surgery or as follow-up. RESULTS: There was no difference in the percentage of
      gallbladder emptying between the bethanechol provocation test +ve and bethanechol
      provocation test -ve groups. Fifty-three percent of bethanechol provocation test
      +ve patients and 54% of bethanechol provocation test -ve patients still remained
      symptomatic 6 months after surgery. Conclusion. Gallbladder pain provoked by
      bethanechol does not predict symptom relief after cholecystectomy.

PMID- 15506669
TI  - A case with intestinal lymphangiectasia successfully treated with slow-release
      octreotide.
AB  - Intestinal lymphangiectasia is one of the protein-losing enteropathies. Herein, a
      case with intestinal lymphangiectasia responded well to diet and octreotide is
      presented.

PMID- 15506670
TI  - Hodgkin' s disease with fulminant non-alcoholic steatohepatitis.
AB  - We report a woman with daily febrile episodes who developed fulminant hepatic
      failure. A percutaneous liver biopsy demonstrated non-alcoholic steatohepatitis,
      with no evidence of neoplastic infiltration. Post-mortem examination revealed
      stage IV Hodgkin's disease with trivial liver involvement. Rapidly progressive
      steatohepatitis causing acute liver failure may be a paraneoplastic presentation
      of Hodgkin's disease, possibly mediated by cytokines.

PMID- 15506671
TI  - Coeliac disease in Middle Eastern countries: a challenge for the evolutionary
      history of this complex disorder?
AB  - About 10,000 years ago domestication and farming of wheat and other cereals
      developed in the 'Fertile Crescent', an area including modern Turkey, Iraq and
      Iran. Agriculture then slowly spread from Middle East to Europe. Coeliac disease
      is the permanent intolerance to dietary gluten, the major protein component of
      wheat. It has been until relatively recently hypothesised that wheat consumption
      exerted a negative selective pressure on genes predisposing to coeliac disease,
      eventually leading to higher coeliac disease frequency in Northeastern Europe
      because of lack of exposure to cereals. This theory is at variance with recent
      studies showing that coeliac disease is as common in Middle Eastern countries as
      in Europe. High prevalence of coeliac disease has been found in Iran, in both the
      general population and at-risk groups, e.g. patients with irritable bowel
      syndrome or type 1 diabetes. Clinical manifestations of coeliac disease vary
      markedly with the age of the patient, the duration and the extent of disease.
      Clinical studies showed that presentation with non-specific symptoms or no
      symptoms is as common in the Middle East as in Europe. Wheat represented a major
      component of the Iranian diet for many centuries and it may be argued that the
      continuous and high level of exposure to wheat proteins has induced some degree
      of immune tolerance, leading to milder symptoms that may be misdiagnosed as
      irritable bowel syndrome or unexplained gastrointestinal disorders. The gluten
      free diet represents a real challenge to both patients and clinicians in this
      area. This is particularly difficult in the absence of any supply for gluten-free
      diet in Middle Eastern countries.

PMID- 15506672
TI  - Prevalence of gallstone disease and related risk factors in 889 diabetic subjects
      of southern Italy.

PMID- 15506673
TI  - Gallstone disease in diabetics: prevalence and associated factors.

PMID- 15506674
TI  - Male-male homosexology: seven short discourses.
AB  - Homosexology is that branch of the science of sexology that deals with same sex
      relationships. It is subdivided into ideation, imagery, and praxis. Praxeology is
      the science of praxis. There are two doctrines by which homosexuality is defined:
      elective and developmental. Elective is like joining a political party and is
      more likely bisexual than exclusively homosexual. Complete developmental
      homosexuality is a state of being and is characteristically immutable. Both types
      of homosexuality are determined multivariately and sequentially, not
      univariately. Male and female mammals are phylogenically programmed to be
      reciprocal, not identical, in the praxeology of their courtship and mating. In
      primate, notably human, evolution, the eyes have taken over from the nose as
      organs of erotic arousal, but the molecular biology of how this happens in
      individual development, gay, straight or ambivalent, remains to be ascertained.
      The different personal histories of homosexual development also remain to be
      ascertained and cataloged.

PMID- 15506675
TI  - A comprehensive team approach to the management of patients with Prader-Willi
      syndrome.
AB  - Prader-Willi syndrome (PWS) is a genetic disorder characterized by extreme
      obesity accompanied by other, multisystem clinical manifestations encompassing
      both physical and behavioral/cognitive abnormalities. The multi-dimensional
      problems of patients with PWS cannot be treated with a single intervention and
      benefit from a team approach to management to optimize outcomes. Childhood
      stature below target height and reduced final height are some defining
      characteristics of PWS, and compelling evidence from growth hormone (GH)
      treatment trials suggests that hypothalamic GH deficiency exists. Treatment with
      GH has been shown to increase height velocity in children with PWS, decrease
      weight-for-height index values and body fat mass, and have a positive effect on
      lean body mass during at least the first year of therapy. In addition to medical
      concerns, the behavioral manifestations, including an uncorrectable deficit in
      appetite control, and cognitive limitations associated with PWS, require long
      term multidisciplinary management.

PMID- 15506676
TI  - Plasma peptide YY and ghrelin levels in infants and children with Prader-Willi
      syndrome.
AB  - An insatiable appetite is a cardinal feature of Prader-Willi syndrome (PWS) with
      stomach rupturing as a reported consequence. Peptide YY, secreted by the
      intestine and released post-prandially, inhibits appetite, while ghrelin,
      secreted by the stomach during mealtime hunger, stimulates appetite. Both peptide
      YY and ghrelin act at the brain level, particularly the hypothalamus. Recently,
      plasma ghrelin levels were reported to be elevated in children and adults with
      PWS but peptide YY levels have not been studied in this syndrome or ghrelin in
      infants with PWS. To further address the abnormal eating behavior in PWS, we
      obtained fasting plasma peptide YY and ghrelin levels in 12 infants and children
      with PWS ranging in age from 2.5 months to 13.3 years and compared them with
      values from normal populations reported in the literature. Plasma ghrelin levels
      in our patients with PWS were similar to those of other children with PWS and
      were significantly higher than those reported in obese children without PWS. Our
      infants with PWS had similar plasma ghrelin levels compared with our children
      with PWS but peptide YY levels in our children and infants with PWS were lower
      than reported in similarly aged individuals without PWS. In addition, we
      performed preliminary gene expression analysis of ghrelin and peptide YY and
      their receptors in patients with PWS using established lymphoblastoid cell lines
      but gene expression did not correlate with plasma ghrelin or peptide YY levels.

PMID- 15506677
TI  - Glycemic control with metformin or insulin therapy in adolescents with type 2
      diabetes mellitus.
AB  - BACKGROUND: Only metformin and insulin are approved by the FDA for adolescents.
      OBJECTIVE: To study the efficacy of insulin versus metformin in adolescents with
      type 2 diabetes mellitus (DM2) and examine whether psychosocial factors affect
      therapeutic efficacy. METHODS: Phase I involved a retrospective examination of
      the medical records of 18 adolescents with DM2. Glycemic control was evaluated by
      mean HbA1c. We tested for relationships between glycemic control and BMI, number
      of outpatient visits per year, and self-reported compliance. Phase II employed a
      pilot questionnaire. RESULTS: Glycemic control deteriorated when therapy was
      changed from insulin (HbA1c, 5.0+/-2.6% [SD]) to metformin (8.4+/-2.9%; p <0.05).
      Self-reported compliance positively predicted glycemic control (p <0.005) and
      inversely correlated with degree of weight loss (p <0.05). Pilot questionnaire
      data suggested that patients may perceive their DM as less serious when treated
      with metformin. CONCLUSIONS: Metformin was often ineffective in our adolescents
      with DM2 and compliance was a major factor. Altered perception of the seriousness
      of their DM may have influenced adherence to therapy.

PMID- 15506678
TI  - Treatment to near adult stature of patients with myelomeningocele with
      recombinant human growth hormone.
AB  - We evaluated near adult statural outcome of treating growth hormone (GH)
      deficient children (peak GH values <10 ng/ml) with myelomeningocele (MMC) with
      0.3 mg/kg/week of recombinant human GH. Retrospective evaluation of 20 patients
      (12 males) who were consistently measured using recumbent length and who had
      achieved more than 90% of their adult stature on GH treatment were included.
      Pretreatment scoliosis was present in 13 patients (<30 degrees); 16 patients had
      lumbar level of lesion, while four had sacral level of lesion; 19 of 20 had a
      ventriculoperitoneal shunt. During GH treatment, two girls were successfully
      treated with leuprolide acetate for precocious puberty, two patients were
      concurrently treated for hypothyroidism and were euthyroid. Standard deviation
      score (SDS) for recumbent length at near adult stature increased in comparison to
      the general adult population and untreated adults with MMC (-2.6 to -1.4 and
      +0.6, respectively, p <0.001). Fifteen of 20 patients at near adult stature were
      above the 3rd percentile of current United States growth charts. These patients
      were less overweight as body mass index (BMI) was less than untreated shorter
      adults with MMC (p <0.01 for females, <0.001 for males). Scoliosis did not
      progress. CONCLUSION: Near adult stature for GH-treated children with MMC is
      significantly greater than untreated adults with MMC. Relative obesity is
      decreased with significant improvement of BMI. This is the first report of
      statural outcome near completion of growth for GH-treated children with MMC.

PMID- 15506679
TI  - A high prevalence of consanguineous and severe congenital hypothyroidism in an
      Iranian population.
AB  - To determine the incidence of permanent congenital hypothyroidism (CH) in Tehran
      and Damavand, cord blood spots were collected from February 1998-August 2002 and
      infants with TSH > or =20 mU/l were recalled. CH was confirmed in neonates (aged
      > or =7 days) with serum TSH >10 mU/l and T4 <84 nmol/l. Cases were followed up
      until September 2003. Dysgenesis was detected by thyroid imaging. In eutopic
      cases, serum TSH and T4 measurements following levothyroxine discontinuation (2-3
      years of age) confirmed dyshormonogenesis and transient CH. Of 35,067 neonates,
      373 (1.06%) were recalled and 25 (1:1,403 births) had permanent CH (six had
      transient CH and four remain unknown). Dysgenesis was detected in 18 (1:1,948
      births) and dyshormonogenesis in seven (1:5,010 births) infants. Parental
      consanguinity was present in 10 (55.6%) dysgenetic, three (42.9%)
      dyshormonogenetic, and overall 6,648 (28.6%) of 23,227 screened infants. Odds
      ratio (95%CI(OR)) of consanguinity in permanent CH and dysgenesis was 2.75 (1.17
      6.47) and 3.74 (1.33-10.52), respectively. The high prevalence of parental
      consanguinity in infants with permanent CH warrants genetic assessment.

PMID- 15506680
TI  - Reversible mitral valve prolapse and mitral regurgitation in children with
      Graves' disease.
AB  - An association between mitral valve prolapse (MVP) and hyperthyroidism has been
      described in adults. However, the long-term prognosis when associated with
      significant mitral regurgitation remains unclear. Three consecutive children with
      Graves' disease were found to have a loud mitral regurgitation murmur (grade
      III/VI) and echocardiographic evidence of MVP with moderate mitral regurgitation.
      The cardiac manifestations included palpitations, exertional dyspnea, and
      exercise intolerance. The electrocardiograms at presentation were sinus
      tachycardia in all cases. All had hyperthyroidism and positive thyroid
      antibodies. Exophthalmos occurred in two and appeared later than the cardiac
      symptoms in one. The cardiac murmur disappeared in all patients when antithyroid
      agents controlled the hyperthyroidism. Follow-up echocardiography showed normal
      in one and MVP with mild mitral regurgitation in two. We conclude that MVP and
      significant mitral regurgitation can occur in children with hyperthyroidism,
      especially those with Graves' disease. The prognosis is good after adequate
      medical control of the hyperthyroidism.

PMID- 15506681
TI  - Lack of association of birth size with polymorphisms of two imprinted genes,
      IGF2R and GRB10.
AB  - Little is known about the determinants of birth size variability among
      individuals. Maternal and nutritional factors have been studied, but familial
      clustering suggests genetic factors as well. As a first step in testing this
      hypothesis, we examined common sequence variants in IGF2R and GRB10, two genes
      involved in the regulation of growth and subject to parental imprinting. The
      IGF2R gene was scanned with five polymorphisms spanning the coding and 3'-UTR for
      possible association with birth size in a set of 97 normal newborns in Greece. In
      addition, a silent SNP in GRB10 exon 2 was similarly tested as an exploratory
      first step. Birth weight and length were compared between groups of newborns
      divided according to which allele they had received from heterozygous parents. No
      significant differences were found between alleles in either gene, examined
      either by parental origin or in aggregate. Thus, we found no evidence that IGF2R
      variants modulate intrauterine growth within the normal range. If such variants
      exist in GRB10, they are not in linkage disequilibrium with the marker studied.

PMID- 15506682
TI  - Analysis of growth during prepubertal years in long-term survivors after
      pediatric orthotopic liver transplantation.
AB  - BACKGROUND: Growth after pediatric liver transplantation (LT) has been the
      subject of reviews. The conclusions have not been consistent. OBJECTIVE: To
      describe post-LT growth patterns in prepubertal liver transplant recipients and
      identify variables affecting their growth. METHODS: Sixty-seven prepubertal
      transplant recipients met the inclusion criteria. Variables assessed were age,
      sex, pretransplant lack of growth, type of transplantation, primary diagnosis,
      liver and kidney function at one year post-LT, complications and
      retransplantation, prednisone therapy duration, allograft rejection episodes
      during the first year, cholesterol, triglycerides and immunosuppressive regimen.
      Mean follow-up was 3.5 years (range: 2-6 years). RESULTS: Growth according to
      baseline z-score, indications for transplantation and steroid withdrawal showed
      significant differences at 2 years post-LT. CONCLUSIONS: The causes of poorest z
      scores in height post-LT were: height z-scores under -2.0 at transplantation,
      metabolic diagnosis, and use of steroids beyond 1 year post-LT.

PMID- 15506683
TI  - Early adrenarche in normal prepubertal girls: a prospective longitudinal study.
AB  - OBJECTIVE: To study basal and ACTH stimulated levels of dehydroepiandrosterone
      (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstenedione (A4), and
      cortisol (F) in healthy girls during prepuberty. PATIENTS: Six prepubertal girls,
      ages 3.7-10.9 years. STUDY DESIGN AND MEASUREMENTS: The six girls underwent a
      physical examination and an acute ACTH stimulation test on a yearly basis. Serum
      DHEA, DHEAS, A4, and F at 0 min (Steroid0) and 60 min (Steroid60) after 0.25 mg
      ACTH1-24 i.v., and the net increment (delta Steroid60-0) were calculated.
      RESULTS: DHEAS0, DHEAS60, DHEA0, DHEA60 and A40 were positively correlated to
      chronological age. DHEAS0 and DHEAS60 levels rose gradually beginning at 6.1-7.0
      years of chronological age, and were found to be significantly different at 9.1
      10.0 years and 10.1-11.0 years of age, compared to the median values obtained at
      < or =6.0 years of age. There was a tendency for DHEA0, DHEA60, and A40 to
      increase beginning at 9.1-10.0 years of age. Net increment values of all hormones
      did not change throughout the study. CONCLUSION: An increase in the circulating
      level of DHEAS appears to be the first event observed during adrenarche, prior to
      clinical evidence of the process.

PMID- 15506684
TI  - Adrenal and ovarian hormonogenesis in a teenage girl with congenital lipoid
      adrenal hyperplasia (CLAH).

PMID- 15506685
TI  - Turner's syndrome and benign intracranial hypertension with or without growth
      hormone treatment.

PMID- 15506686
TI  - Transient reduction in the posterior pituitary bright signal preceding water
      intoxication in a malnourished child.
AB  - We describe a 4 year-old boy with hypothalamic dysfunction and weight loss,
      attributed to psychosocial deprivation. Reduced intensity of the posterior
      pituitary bright signal (PPBS) on MRI, associated with a normal urinary
      concentrating ability, was documented in the 24 hours prior to the development of
      the syndrome of inappropriate secretion of antidiuretic hormone (ADH) and severe
      hyponatraemia. The PPBS was normal on MRI 2 months later, following weight gain
      and resolution of the other hypothalamic abnormalities. This report shows that
      the abnormalities of ADH associated with decreased intensity of the PPBS include
      increased secretion and abnormal regulation as well as ADH deficiency. The
      association of osmotically unregulated ADH secretion with undernutrition and
      stress suggests that particuar caution should be used when fluid intake in such
      children is not driven by thirst.

PMID- 15506687
TI  - Idiopathic hypercalcemia and eosinophilic fasciitis: a novel association.
AB  - A 15 year-old boy presented with moderate hypercalcemia (serum calcium 3.35
      mmol/l) and eosinophilic fasciitis. An extensive search for a cause of
      hypercalcemia or underlying malignancy proved negative. Glucocorticoid treatment
      resulted in significant clinical improvement and resolution of the hypercalcemia.
      This report describes the novel association of hypercalcemia with eosinophilic
      fasciitis, with potential implications for the role of inflammatory mediators.

PMID- 15506688
TI  - A calcium aluminate cement as restorative material in Class V cavities.
AB  - Recently a calcium aluminate cement (Doxa Certex, Uppsala, Sweden) has been
      developed intended to be used as direct restorative filling material. The aim of
      this study was to evaluate intra-individually the experimental calcium aluminate
      cement (CAC) and a resin composite (RC;Tetric Ceram) in Class V restorations.
      Each of 46 participants received at least one pair of restorations of the same
      size, one CAC and one RC. The 119 restorations were evaluated clinically,
      according to slightly modified USPHS criteria, at baseline, after 6 mths, 1, 2
      and 3 yrs. None of the patients reported post-operative sensitivity. At 3 yrs,
      111 restorations were evaluated. Significantly better clinical durability was
      shown for RC. Two non-acceptable CAC restorations were observed at 6 months, 3
      CAC and 1 RC at 12 months, 5 CAC and 2 RC at 24 months, and 8 CAC at 36 months.
      This resulted in a cumulative failure frequency of 32% for the CAC material and
      5% for the RC material. Main reason for failure for the CAC was total or partial
      lost restorations, and for the RC lost restorations. It can be concluded that the
      CAC showed a non-acceptable clinical failure rate for Class V restorations.

PMID- 15506689
TI  - Comparing caries risk factors and risk profiles between children and elderly.
AB  - The aim of this study was to compare the caries risk profiles of children and
      elderly, the actual annual caries increment and the impact of some selected
      caries related factors. The risk profiles were created by a computerised risk
      assessment program, the Cariogram, which evaluates data and presents the weighted
      and summarized result as one figure, illustrating the 'percent chance of avoiding
      caries' in the future. The data used originated from two separate longitudinal
      studies illustrating the Cariogram's capacity to assess caries risk. One study
      comprised about 400 children; the other included about 150 elderly. At baseline,
      information on past caries experience, diet, oral hygiene and use of fluoride was
      obtained. Saliva analyses included mutans streptococci and lactobacilli,
      buffering capacity and secretion rate. The caries risk was assessed and after two
      and five years, respectively, caries was re-evaluated and the incidence was
      compared with the predictions. Fifty percent of the children, but only two
      percent of the elderly appeared in the lowest caries risk group. Of the elderly,
      26% belonged to the highest caries risk group versus 3 % of the children. The
      mean DFS increment per year for the total group of children was 0.4 +/- 0.8 (SD)
      and 1.2 +/- 1.9 for the elderly. Individual factors contributing significantly to
      the higher risk profiles for the adults were higher plaque scores, higher counts
      of mutans streptococci and lower buffering capacity. Over all, the risk for
      caries, as assessed by the Cariogram, was twice as high for the elderly.

PMID- 15506690
TI  - Changes in caries experience among 6-year-olds in Blekinge, Sweden between 1994
      and 2000.
AB  - For 6-year-old children in the County of Blekinge, the goal was that > 65 percent
      should have dmft = 0 in the year 2000. To formulate this goal a study on
      prevalence and distribution of caries in 6-year-old children was performed in
      1994. The aim of the present study was to evaluate whether the dental health goal
      for the year 2000 was achieved and compare clinical data regarding oral status in
      children in 1994 and in 2000. The material comprised a random sample of 225
      children. The studyfrom year 1994, which included 213 children, was repeated. A
      clinical investigation was performed and completed with bite-wing radiographs on
      individual indication, whenever the proximal surfaces could not be inspected
      clinically due to close and broad contact. In addition, the parents were asked
      questions about toothbrushing and use of fluoride tablets. 53 percent of the
      children showed healthy teeth with no initial caries lesions or restorations
      compared to 35 percent in 1994. The pattern of dental health was still very
      skewed among the children. The children with nine or more decayed surfaces
      increased from 2 percent in 1994 to almost 4 percent in 2000. The number of
      fissure sealings performed had increased between 1994 and 2000 by almost 50
      percent in both primary molars and first permanent molars. However,the use of
      fluoride tablets had decreased from 20 percent in 1994 to 7 percent of the
      children in 2000. The data showed a decline in prevalence of dmf teeth and an
      increase in the percent of caries-free children but the difference was not
      significant on the 5% level. However, as 47% of the children were in need of
      restorative treatment, our dental health goal was not achieved. We also recommend
      that our preventive program with focus on primary prevention and individual risk
      assessment should also be targeted at the whole population of pre-school children
      and their parents.

PMID- 15506691
TI  - Reduction of absorbed doses to the thyroid gland in orthodontic treatment
      planning by reducing the area of irradiation.
AB  - The objectives were to study whether a smaller area of irradiation resulted in a
      significant reduction in the dose of absorbed radiation to the thyroid gland for
      three radiographic modalities commonly used in cephalometric treatment planning.
      The aim of this research, was to study the effect of the field size on the
      absorbed dose of radiation to the thyroid gland, as measured with
      thermoluminescent dosimeters (TLD) in a phantom. Three radiographic modalities
      were used: panoramic, cephalometric, and intra-oral. For each modality, a large
      and a small collimator were used. A Rando Alderson phantom comprising a natural
      human cranium and cervical vertebrae embedded in a thermoplastic material
      simulating human soft tissue was used to measure absorbed dose to the thyroid
      gland. These measurements were made using lithium fluoride (LiF) TLDs. A
      significant reduction in absorbed dose to the thyroid gland was obtained by
      reducing the collimator in all three modalities. A 15% reduction in absorbed dose
      to the thyroid gland was achieved for the combination of small field sizes
      compared to the combination of large field sizes. Combining the use of selection
      criteria together with a smaller field of irradiation than normally used made a
      reduction in absorbed dose to the thyroid gland of around 30% possible.

PMID- 15506692
TI  - Bone quality.

PMID- 15506693
TI  - The quality of bone: a "magic natural alloy".

PMID- 15506694
TI  - Epidemiology and nutritional risk factors.

PMID- 15506695
TI  - Modifying nutritional risk factors.

PMID- 15506696
TI  - Bone modeling and remodeling: from biology to clinical application.

PMID- 15506697
TI  - Quantitative ultrasound assessment of bone.
AB  - In the last two decades, several non-invasive techniques have been developed to
      measure bone density at axial and peripheral skeletal sites. The dual-energy X
      ray absorptiometry (DXA) technique allows accurate measurement of bone density,
      but does not provide information about the structural and qualitative features of
      bone, which play an important role in fracture risk determination. Increasing
      interest in quantitative ultrasonography (QUS) has recently developed; it may be
      considered a safe and quite inexpensive diagnostic technique. Ultrasound devices
      routinely measure two parameters: broadband ultrasound attenuation (BUA) and
      speed of sound (SOS). Two other parameters, stiffness and index of consistency
      (QUI), can be derived from BUA and SOS. SOS is influenced by the elasticity of
      bone as well as by its density. BUA is determined by mechanisms of diffraction,
      scattering and absorption in the bone, marrow and soft tissue. Absorption
      predominates in cortical bone and scattering in trabecular bone. BUA is a measure
      of the approximately linear frequency dependence of ultrasound attenuation.
      Several QUS devices are now available for clinical use for measuring various
      parameters at skeletal sites with different contents of trabecular and cortical
      bone. Standardization of instruments is one of the major limitations of this
      technique today. Many studies have demonstrated that BUA and SOS, measured at any
      level, can discriminate normal subjects from osteoporotic patients. Moreover,
      there is evidence documenting the ability of QUS to predict osteoporotic fracture
      risk and to give further BMD-independent information on bone. QUS at the heel can
      now be considered as an alternative technique to identify subjects with a high
      risk of bone fragility. Further studies are needed for better definition of the
      role of QUS in clinical practice.

PMID- 15506698
TI  - Is BMD measurement an adequate surrogate for anti-fracture efficacy?

PMID- 15506699
TI  - Bone markers: biochemical and clinical significance.

PMID- 15506700
TI  - Prevent, treat and maintain: a new goal for osteoporosis management in clinical
      practice.

PMID- 15506701
TI  - A reappraisal of therapeutic approaches to osteoporosis.

PMID- 15506702
TI  - [Biological availability of ophthalmic preparations. 2. Ophthalmic therapeutic
      systems].
AB  - Ophthalmic therapeutic systems, which rank among the drugs of the second and
      third generation, make possible prolonged and controlled drug release, or the
      introduction of the drug direct into the site of action (a specific eye tissue)
      with minimal distribution into the adjacent tissues. The group mainly consists of
      solid ophthalmic preparations, in a lesser extent there are systems developed
      from hydrogels, colloidal carriers, etc. The present review lists both insoluble
      ophthalmic therapeutic systems and those soluble in water (degradable, erodible).
      Insoluble systems include membrane-controlled ophthalmic therapeutic systems
      (e.g. Ocusert), therapeutic eye lenses, eye implants, and other insoluble
      preparations. In the group of soluble preparations, topical inserts and systems
      are described, which are introduced into eye tissues as implants or injections.

PMID- 15506703
TI  - [Photodynamic therapy as a new prospective method for cancer treatment. I.
      History, basic principles].
AB  - Photodynamic therapy (PDT) is a new method for the treatment of both cancer or
      non-cancer diseases. It combines three basic elements (a photosensitizer, light,
      oxygen), every single one with no toxicity or biological activity. The
      photosensitizer (PS) is activated by light and it gets excited. It transfers
      absorbed energy from this excited form to oxygen forming reactive oxygen species
      (ROS), mainly singlet oxygen. Then ROS attack surrounding biomolecules, inhibit
      their biological function leading in the end to a cell death. The complete
      destruction of the tumour is provided not only by a direct effect on the cells,
      but also a vasculature shutdown (leading to nourishment and oxygen depletion) and
      an activation of the immunity response play an important role in this process.
      The present paper proposes to introduce the readers to the history and basic
      principles of PDT from the point of view of either the physical mechanism of PS
      activation or biological effects on the target tissue (on molecular, subcellular,
      cellular, and tissue levels).

PMID- 15506704
TI  - [HPLC determination of diperodon enantiomers in blood serum by using teicoplanin
      chiral stationary phase].
AB  - The chiral stationary phase on the base of teicoplanin and the polar-organic
      mobile phase methanol/acetonitrile/acetic acid/triethylamine 45/55/0.3/0.2 was
      used for the separation of diperodon enantiomers. The developed method was
      suitable to determine the enantiomers in blood serum up to 0.5 microg/ml. The
      degradation of diperodon enantiomers was studied in serum by an in vitro method
      and the experimental rate constants were determined.

PMID- 15506705
TI  - [Validation of an HPLC method for the analysis of decomposition products in
      injectable diazepam].
AB  - Diazepam is an important drug from the group of benzodiazepines, used in clinical
      practice for its sedative, hypnotic, anticonvulsive, myorelaxant, and primarily
      anxiolytic effects. Several kinetic studies have been published which show that
      diazepam is a drug sensitive to hydrolysis both in acid and alkaline media. The
      present study aimed to elaborate and validate a simple and rapid HPLC/UV method
      for simultaneous analysis of three decomposition products of diazepam in the
      presence of diazepam and to apply it also on the control of stability of the
      injectional solution of diazepam. The optimization of chromatographic conditions
      resulted in the use of the high-performance chromatographic column Zorbax ODS,
      the mobile phase represented by a mixture of acetonitrile/water in a ratio of
      60/40 (w/w, %), flow rate 1.5 ml/min, and spectrophotometric detection at 242 nm.
      The elaborated method and the employed chromatographic system were successfully
      validated and they can be used in practice in the control of stability of
      injection solution of diazepam.

PMID- 15506706
TI  - [Patient-oriented advice on pharmaceuticals and its position on pregraduate
      education of pharmacists].
AB  - Patient-oriented information on pharmaceuticals has gradually become the dominant
      activity of the pharmacist in the community pharmacy. It is therefore necessary
      to devote sufficient attention to the quality of patient oriented advice already
      in the course of the pregraduate education of pharmacists so that new graduates
      who start practising may be prepared both theoretically and practically to cope
      with the requirements they encounter when working with pharmaceuticals and
      patients under the contemporary conditions. This paper aimed to monitor the
      present state of instruction of undergraduates as far as the items of information
      given to patients are concerned. The results of the study propose to the
      instructor possible ways of motivating and guiding the undergraduates to the
      correct approach of the use of information given to patients are concerned. The
      results of the study propose to the instructor possible ways of motivating and
      guiding the undergraduates to the correct approach of the use of information on
      pharmaceuticals as well as the methods items of employng these items of
      information on dispensing.

PMID- 15506707
TI  - [Unit dose systems prepared for geriatric patients. I].
AB  - The project was carried out to facilitate and improve the quality of the use of
      drugs by geriatric patients aiming at the observation of the therapeutic regimen
      and the improvement of their compliance. The group under study comprised 15
      clients living in a selected old people's home in the city of Brno, for whom the
      pharmacist prepared drugs into one-week blister dispensers on the basis of their
      health dossiers for a period of 6 months (February - July 2002). Polypharmacy
      occured in all patients included into a unit-dose preparation for drugs; they
      took on average 16 drugs in a week. The most frequently administered drugs
      belonged to the ATC groups of psycholeptics, anti-inflammatory and antirheumatic
      agents, peripheral vasodilators, antianaemic agents, cardiac therapy, diuretics,
      and vasoprotectives and venopharmaceuticals. The dimensions of the dispensers
      used and the size of individual blisters in them proved to be sufficient with an
      average number of 11 drugs dispensed weekly. The preparation of one-week drug
      dispensers was also evaluated from the standpoint of time consumption. The
      average time of preperation of dispensers by the pharmacist was 16 minutes 20
      seconds. Time consumption was connected not only with the total number of drugs
      dispensed, but also with the frequency of drug dosing, splitting (halving,
      quartering) of drugs, and frequent changes in medication.

PMID- 15506708
TI  - [Evaluation of water-soluble vitamins in the vitamin preparation Spofavit dragee
      using reversed-phase HPLC].
AB  - A reversed-phase HPLC gradient method with good separation efficiency was
      developed and validated for the evaluation of water-soluble vitamins in the
      pharmaceutical preparation Spofavit dragee. Analyses were performed on a C8
      column (LiChrospher RP-select B), the mobile phase was a mixture of phosphate
      buffer with sodium hexanesulphonate and acetonitrile. Detection was at 280 and
      210 nm. The method is capable within 7 minutes to evaluate 6 water-soluble
      vitamins (ascorbic acid, nicotinamide, panthotenate.Ca, pyridoxine.HCl,
      thiamine.HCl, and riboflavin). All validated parameters of this method are
      discussed; the developed method appeared robust and suitable for evaluation of
      water-soluble vitamins in vitamin preparations.

PMID- 15506709
TI  - [Isolation and characterization of active compounds from Aloe vera with a
      possible role in skin protection].
AB  - Aloe vera is widely used in food supplements, beverages, pharmaceuticals, and
      cosmetics. It has been long recognized as an effective natural remedy for its
      wound-healing properties and its positive influence on other inflammatory skin
      disorders. Major proteins and mono- and polysaccharides were identified and
      analysed from Aloe vera commercial extract. Molecular weight of proteins
      calculated from the sets of molecular weight reference standards, ranged from 70
      kDa for the largest to 14 kDa for the smallest ones. IR spectral analysis of the
      carbohydrate fraction shows that the main carbohydrate copound is acetylated (1 -
      > 4)-beta-D-mannan substituated with D-galactose and D-glucose. The results have
      shown that proteins and polysaccharides are a necessary component in the study of
      biological activity of Aloe vera leaf extract.

PMID- 15506710
TI  - [Abiotic elicitation of the explant culture of Rheum palmatum L. by heavy
      metals].
AB  - Elicitation-produced stress activates the defensive reactions of the plant or
      plant explant, which result, among others, in a change in the transcription of
      the genes coding the enzymes influencing biosynthesis of secondary metabolites.
      The present paper investigated the effect of ions of heavy metals in
      concentrations od 1; 10, and 100 microM on the production of anthracene
      derivatives by the explant culture of Rheum palmatum L. cultivated on Murashige
      Skoog medium with an addition of 10 mg.l(-1) of alpha-naphthylacetic acid. The
      periods of application of elicitation were 6; 24; 48, and 168 hours. It follows
      from the results that the applied abiotic elicitation positively influenced the
      production mainly in suspension culture. The maximal increase in the content of
      anthracene derivatives versus the control by 66% was observed after 48-hour
      action of 10 microM concentration of cadmium chloride. Aluminium chloride
      produced the largest increase in the production after 6-hour application of a 100
      microM concentration, when in comparison with the control culture the production
      was stimulated by 60%.

PMID- 15506711
TI  - [Analytical evaluation of 1-(dipropalamino-3-piperidine-propane-1-yl)-3
      pentyloxyphenylcarbamate (CK-3635)].
AB  - The paper presents the results of analytical and pharmacological evaluation and
      study of some physicochemical properties of a potential drug marked as CK-3635
      with high local anaesthetic activity. The structure of the substance has been
      confirmed by IR and UV spectroscopy. The melting point, solubility, partition
      coefficient, capacity factor, surface activity, and dissociation constant were
      determined. The chromatographic behaviour of the drug on a thin layer was also
      investigated. For the content determination, spectrophotometry in the ultraviolet
      region of the spectrum at the wavelenght of the second absorption maximum of the
      substance, the titration in the two-phases ambient, and high-performance liquid
      chromatography were used.

PMID- 15506712
TI  - [Examination of the stability of hydrogen peroxide solutions].
AB  - Reliable stabilization of the pharmaceutical preparation and the active
      ingredient remains one of the most important problems of world pharmacy because
      pharmaceutical preparations are not systems which are stable without limitation.
      The patient must receive a quality drug and that is why the question of stability
      is paid grest attention to not only in research and development, industrial
      manufacture, but also in distribution. The measure of stability is the expiration
      period. Diluted solution of hydrogen peroxide (3% solution) still belongs to the
      most widely used and at the same time the most easily accessible disinfectants.
      In practice it is common both in Slovakia and abroad. It is used in several
      concentrations. One of its most important disadvantages is its limited stability,
      which markedly decreases its expiration period. The present paper investigates
      the stability of hydrogen peroxide solutions of routinely used concentrations
      (3%, 6%, and 10%) without and with a stabilizing additive (phenacetin) prepared
      in the pharmacy and stored under different conditions for the period of their
      expected usability. The content of hydrogen peroxide was assayed by the
      pharmacopoeial method in 7-day time intervals. All concentrations of 3%, 6%, and
      10% hydrogen peroxide were found to fulfil the conditions for stability in the
      period of time under study. Their concentration did not fall below the limit od
      90% of the content of the active ingredient, and storage under decreased
      temperature proved to be more suitable. Storage of hydrogen peroxide in the light
      is inadmissible. When the conditions of storage are observed, the required
      therapeutic effect of hydrogen peroxide solution can be expected for the period
      of three months.

PMID- 15506713
TI  - [Study of mixed dry binders in directly compressible lactoses and
      microcrystalline cellulose].
AB  - The paper evaluated the compressibility of dry binders prepared in the ratios of
      3:1, 1:1, and 1:3 from Pharmatosa DCL 15 and DCL 21 and Avicel PH 200, and the
      sensitivity of the mixtures to an addition of the lubricant magnesium stearate
      from the standpoint of the effect on the strength of tablets. Mixtures of
      lactoses with Avicel PH -200 in a ratio of 3:1 proved to be most advantageous.
      The strengths of tablets made of these mixtures oscillated in the optimal range
      and they showed the least sensitivity to the added lubricant. An increase in
      stearate concentration did not result in a marked decrease in the strength of
      compacts. Pharmatosa DCL 21 in a mixture with Avicel PH 200 yielded stronger
      compacts at lower compression force than Pharmatosa DCL 15.

PMID- 15506714
TI  - [Catheter cryoablation for the treatment of supraventricular arrhythmias].
AB  - Catheter ablation is a radical treatment for various severe and drug-refractory
      arrhythmias. Radiofrequency is the reference energy for ablation, but has some
      limitations. Cryoenergy gradually freezes myocardial tissue, allowing the
      consequences to be predicted before inducing the lesion. Furthermore, the lesions
      are better-circumscribed and less thrombogenic than those induced by
      radiofrequency. Twenty-two patients (12 women) aged from 20 to 79 years with drug
      refractory supraventricular arrhythmias underwent cryoablation. The ablation
      catheter was cooled by nitrous oxide expansion. The electrophysiological
      properties of the tissue are reversibly lost at a temperature of -30 degrees C,
      allowing cryomapping. When the appropriate target has been located, the
      temperature is reduced to -70 degrees C. The cryoablation is painless. The
      procedure was initially successful in all 12 patients with atrionodal reentrant
      tachycardias, usually after one or two applications. However, during the 8-month
      follow-up period, slower, transient tachycardia recurred in 3 patients. We
      observed no cases of atrioventricular (AV) block, a possible complication of
      radiofrequency. Cryoablation was successful and safe in two patients with an
      accessory pathway (Kent). In eight patients with atrial fibrillation and
      uncontrolled ventricular tachycardia, cryoablation was used with the aim of
      slowing nodal conduction. Initial success was obtained in 7 cases (3 modulations
      and 4 complete AV blocks) but only persisted in four cases, suggesting that more
      applications should be used or different sites targeted. The efficacy and safety
      of cryoablation make it an attractive option for the ablation of small substrates
      close to the nodo-Hisian tissue (atrionodal reentries and accessory pathways).
      New criteria must be developed to define long-term success of cryoablation of the
      AV node, which is successful in the acute setting.

PMID- 15506715
TI  - [From Morvan's disease to potassium channelopathies].
AB  - The term Morvan's disease, first coined in 1890, is still in use, although the
      generic term neuromyotonia--which is not exempt from criticism--has largely
      superseded it. Symptoms and signs are variable, ranging from benign painful
      fasciculations, pseudomyotonic cases, rigid forms, cases in which central nervous
      system features are also present (with, in addition to nerve hyperexcitability,
      agitation, confusion, delirium, insomnia, hyperhidrosis and tachycardia). A
      distal peripheral motor nerve is the origin of nerve hyperexcitability. There is
      growing evidence that autoimmunity is involved in the pathogenesis of many cases.
      Antibodies to voltage-gated potassium channels are detected in the serum of many
      patients with peripheral nerve hyperexcitability. Other cases are probably
      genetic. Inherited disorders are related to episodic dominant ataxia type 1, with
      the same mutation of a gene coding for potassium channel subunit Kv 1-1. Many
      inappropriate or non specific names are used to refer to peripheral nerve
      hyperexcitability. Isaacs syndrome, voltage-gated potassium channelopathy, or
      Morvan's syndrome are suggested.

PMID- 15506716
TI  - [Genetics of hereditary iron overload].
AB  - The classification of hereditary abnormalities of iron metabolism was recently
      expanded and diversified. Genetic hemochromatosis now corresponds to six
      diseases, namely classical hemochromatosis HFE 1; juvenile hemochromatosis HFE 2
      due to mutations in an unidentified gene on chromosome 1; hemochromatosis HFE 3
      due to mutations in the transferrin receptor 2 (TfR2); hemochromatosis HFE 4
      caused by a mutation in the H subunit of ferritin; and hemochromatosis HFE 6
      whose gene is hepcidine (HAMP). Systemic iron overload is also associated with
      aceruloplasminemia, atransferrinemia and the "Gracile" syndrome caused by
      mutations in BCS1L. The genes responsible for neonatal and African forms of iron
      overload are unknown. Other genetic diseases are due to localized iron overload:
      Friedreich's ataxia results from the expansion of triple nucleotide repeats
      within the frataxin (FRDA) gene; two forms of X-linked sideroblastic anemia are
      due to mutations within the delta aminolevulinate synthetase (ALAS 2) or ABC-7
      genes; Hallervorden-Spatz syndrome is caused by a pantothenate kinase 2 gene
      (PANK-2) defect; neuroferritinopathies; and hyperferritinemia--cataract syndrome
      due to a mutation within the L-ferritin gene. In addition to this wide range of
      genetic abnormalities, two other features characterize these iron disorders: 1)
      most are transmitted by an autosomal recessive mechanism, but some, including
      hemochromatosis type 4, have dominant transmission; and 2) most correspond to
      cytosolic iron accumulation while some, like Friedreich's ataxia, are disorders
      of mitochondrial metabolism.

PMID- 15506717
TI  - [Should we support large-scale screening for genetic haemochromatosis in
      France?].
AB  - Genetic hemochromatosis meets the principal World Health Organization criteria
      for diseases warranting systematic population screening. Indeed, it is a
      frequent, late-onset, severe disease that is easy to diagnose and cure. However,
      its penetrance is much lower than thought prior to the discovery of the HFE1
      gene, whose C282 Y mutation is responsible for more than 95% of cases with
      phenotypic expression. Moreover, several questions remain to be answered, notably
      concerning practical modalities [genotypic or phenotypic screening? at what age?,
      etc.], the risk of genetic discrimination, and cost-effectiveness. Current
      recommendations should include [i] broad information of the general population
      and GPs on early symptoms, [ii] transferrin saturation assay in all patients with
      symptoms compatible with hemochromatosis and, when elevated, genetic testing, the
      cost of which should be covered by public health insurance, [iii] both phenotypic
      and genotypic screening of all proband families, and [iv] implementation of
      regional and national pilot studies aimed at assessing disease penetrance and the
      acceptability and cost-effectiveness of large-scale screening.

PMID- 15506718
TI  - [Circular insanity, 150 years on].
AB  - On January 31 1854, Jules Baillarger delivered a lecture to the French Imperial
      Academy of Medicine describing a new variety of insanity, "la folie a double
      forme", whose main feature was the occurrence of both manic and depressive
      episodes in the same patient. Immediately his colleague Jean-Pierre Falret
      pointed out that he had already published a description of the same disorder,
      that he had named "folie circulaire" and, on February 14, presented a lecture on
      the subject to the Academy. Baillarger accused him of plagiarism, contending that
      Falret had used the two weeks between the two lectures to attribute the main
      characteristics of la folie a double forme to his folie circulaire, whose
      description now bore little relation to the (very short) previous report that
      Falret had evoked as proof of his priority. Falret subsequently showed great
      restraint in the controversy, while Baillarger reiterated and extended his
      accusations until his death. An objective study of the printed material not only
      establishes Falret's clear priority, but also demonstrates that Baillarger's
      accusations of plagiarism are unfounded, as the descriptions of la folie
      circulaire and la folie a double forme differ on many important points, the first
      being much closer than the second to our present conceptions. Falret's discovery
      is thus a landmark in the nosology of mental disorders. Contrary to the then
      widespread belief in the existence of a single entity--" mental alienation"--with
      several symptomatic manifestations, Falret affirmed that, in psychiatry as in the
      rest of medicine, separate disease entities existed. While their etiology was
      still unknown, they could be distinguished by their syndromic expressions and
      their outcome; on this basis, Falret considered that la folie circulaire was,
      together with general paralysis, the only true mental disorder so far identified.
      His principles were subsequently adopted by Kraepelin, whose main nosological
      concepts, established around 1900, are still in use today. Kraepelin attributed
      most psychotic manifestations to two diseases, namely dementia praecox (later
      renamed schizophrenia) and manic-depressive psychosis; the two differed mainly by
      the progression of the former to a final state of mental deterioration. Falret's
      folie circulaire was incorporated in the second disease, as one of its many
      symptomatic forms. It regained its autonomy only in 1966 when Angst and Perris
      demonstrated the specificity of its heredity and named it bipolar disorder.
      Recent studies suggest that the boundaries of this disorder extend far beyond
      those of its classical description. The so-called bipolar spectrum now includes,
      on the basis of clinical, biological, genetic and therapeutic arguments, the
      manic and hypomanic, and even purely depressive manifestations of mood disorder.
      One hundred and fifty years after its inception, Falret's concept of folie
      circulaire has become one of the main focuses of psychiatric research.

PMID- 15506719
TI  - [From circular insanity (in double form) to the bipolar spectrum: the chronic
      tendency for depressive recurrence].
AB  - From a cycling standpoint, "circular insanity" (Falret) and "dual-form insanity"
      (Baillarger), both described in hospital patients in 1854, are at the severe end
      of the spectrum of what we now call "bipolar disorders". Falret was prescient in
      suggesting that circular insanity was rare in the community, where depressive
      cycles are prevalent. These disorders are now respectively referred to as the
      "hard" (manic-depressive) and "soft" (bipolar spectrum) phenotypes of the
      disorder. This paper focuses on the latter, more prevalent depressive expressions
      of the spectrum, which share with the manic and circular forms a lifelong
      tendency to recur. Their cyclicity may involve putative "clock genes". The
      genetics of psychotic mania overlaps somewhat with the genetics of schizophrenia.
      As regards depressive recurrence, putative genetic factors have been identified,
      including a polymorphism of the serotonin transporter, which significantly
      increases the subject's vulnerability to stress; a mediating pathogenetic
      variable appears to be temperamental dysregulation (e.g. neuroticism and
      cyclothymic lability), which produces hyperemotional reactivity to such
      stressors. The growing recognition that many depressive recurrences belong to a
      broad spectrum, affecting 5-10% of the population, represents a new public health
      challenge. Although the new class of serotoninergic antidepressants offer a
      practical approach to the management of depressive episodes, further research is
      needed to determine the point of the spectrum at which mood-stabilizing therapy
      should be started--and in what combinations--in order to prevent recurrence and
      suicide.

PMID- 15506720
TI  - [Bipolarity: from manic-depressive disease to bipolar disorder].
AB  - Until recently, bipolar disorder was viewed as a relatively rare condition
      characterized by periods of euphoric excitement and depressive retardation which
      was easy to diagnose, and easy to treat thanks with lithium and new prophylactic
      treatments. In fact, bipolar disorder encompasses a variety of conditions, whose
      overall lifetime prevalence in the general population may be between 5 and 8%.
      Long term with lithium and other compounds are very effective but must be
      combined with non pharmacological therapies. Over the past two decades, advances
      in genetic, brain imagings, and biochemical have improved our knowledge on the
      pathophysiological mechanisms underlying these disorders.

PMID- 15506721
TI  - Scanning probe lithography on fluid lipid membranes.
AB  - Scanning probe lithography (SPL) is applied to pattern fluid lipid membranes on a
      solid borosilicate substrate. Grids of metal lines, prepatterned onto the
      substrate by electron beam lithography, serve to partition the supported membrane
      into an array of isolated fluid pixels. By toggling the pH of the surrounding
      solution, the effect of the probe tip on the membrane can be regulated. Alkaline
      conditions favor membrane removal, while neutral pH favors membrane deposition.
      Arbitrary membrane patterns with spatial dimensions limited by the underlying
      grid size can be constructed by sequential SPL membrane removal followed by
      refill with a different membrane type. In the present study, bilayers of unique
      composition fill 1 x 1 mum corrals and were positioned 100 nm apart.

PMID- 15506722
TI  - A high-nuclearity "Celtic-ring" isopolyoxotungstate, [H12W36O120]12-, that
      captures trace potassium ions.
AB  - A high-nuclearity {W36} isopolyoxotungstate cluster, [H12W36O120]12-, with a
      triangular shape has been isolated by using an encapsulating organic cation,
      protonated triethanolamine. In analogy to an 18-crown-6 crown ether, the cluster
      captures a potassium ion, present in trace amounts in the reaction system, within
      its cavity. DFT calculations suggest that the distribution of partial atomic
      charges over the oxygen framework shows maxima at certain "hotspot" sites, which
      imply possible routes for further cluster growth based on the {W36} system.

PMID- 15506724
TI  - Design and STM investigation of intramolecular folding in self-assembled
      monolayers on the surface.
AB  - The rational design of catechol bis-amides rendered molecular structures that
      fold into beta-turn mimics at the interface of HOPG and 1-octanol as demonstrated
      by STM. These self-assembled monolayers provide a prototypical model for linear
      sequences containing more turn mimics, which will allow for true synthetic
      surface confined foldamers.

PMID- 15506723
TI  - Phosphatidylethanolamine-induced cholesterol domains chemically identified with
      mass spectrometric imaging.
AB  - Coexisting liquid phases of model membrane systems are chemically identified
      using imaging time-of-flight secondary ion mass spectrometry (TOF-SIMS). The
      systems studied were Langmuir-Blodgett (LB) model membranes of cholesterol (CH)
      with two different phospholipids, one a major component in the outer plasma
      membrane bilayer leaflet (dipalmitoylphosphatidylcholine (PC)) and the other a
      major component in the inner leaflet (dipalmitoylphosphatidylethanolamine (PE)).
      Binary mixtures of CH with each of the phospholipids were investigated, as well
      as a ternary system. A single homogeneous phase is evident for PC/CH, whereas
      both systems containing PE show lateral heterogeneity with phospholipid-rich and
      CH-rich regions. The interaction between CH and the two phospholipids differs due
      to the disparity between the phospholipid headgroups. Imaging TOF-SIMS offers a
      novel opportunity to chemically identify and differentiate the specific membrane
      locations of CH and phospholipid in membrane regions without the use of
      fluorescent dyes. This unique imaging method has been used to demonstrate the
      formation of micrometer-size CH domains in phosphatidylethanolamine-rich systems
      and is further evidence suggesting that CH may facilitate transport and signaling
      across the two leaflets of the plasma membrane.

PMID- 15506725
TI  - Photochemically knocking out glutamate receptors in vivo.
AB  - AMPA (alpha-amino-3-hydroxy-5-methyl-4-isooxazole) receptors, a major subtype of
      ionotropic glutamate receptors (iGluRs), mediate the majority of the fast
      communication between neurons, and the activity-dependent trafficking of AMPA
      receptors at synapses plays a role in mammalian learning and memory. Here we
      describe the design, synthesis, and evaluation of a photoreactive AMPA receptor
      antagonist that provides a means of "knocking out" AMPA receptors present on the
      surface of cells. The antagonist, 6-azido-7-nitro-1,4-dihydroquinoxaline-2,3
      dione (ANQX), was designed by introducing a photoreactive azido group onto a
      quinoxalinedione inhibitor scaffold. Computational docking of ANQX to the AMPA
      receptor ligand-binding core predicted efficient binding to AMPA receptors.
      Glutamate-evoked currents were reversibly blocked at micromolar ANQX
      concentrations prior to photolysis and irreversibly blocked following photolysis.
      ANQX provides a means of directly evaluating the trafficking of native AMPA
      receptors with unparalleled spatiotemporal resolution.

PMID- 15506726
TI  - Long-range electron transfer across Peptide bridges: the transition from electron
      superexchange to hopping.
AB  - Long-range electron transfer rate constants for complexes of the type
      [(bpy)2RuIIL-Pron-apyRuIII)(NH3)5]5++ proline residues (n) varying from 0 to 9
      were determined by complementary electron pulse radiolysis and flash photolysis
      techniques from the picosecond to the millisecond time scales. The activationless
      kmax values from both techniques coalesce into one data set. The distance
      dependence of the reactions is consistent with a smooth transition from a
      superexchange mechanism with attenuation constant beta = 1.4 A-1 to a hopping
      mechanism with attenuation constant beta = 0.17 A-1. The transition occurs
      between n = 3 and 4 prolines, and the virtual hopping rate constant at the
      shortest distance is about 1 x 106 times slower than that observed for the
      superexchange value.

PMID- 15506727
TI  - High velocity interparticle collisions driven by ultrasound.
AB  - Ultrasonic irradiation of slurries produces high velocity impacts between solid
      metal particles that are sufficient to cause interparticle melting. Sonication of
      5 mum Zn powder as a slurry in alkanes, for example, produces dense agglomerates
      50 mum in diameter consisting of approximately 1000 fused particles. Particle
      size was found to be the most influential parameter in inducing local melting
      during interparticle collisions. Ultrasonic irradiation of mixed powders resulted
      in formation of agglomerates with larger Zn particles "soldered" by the smaller
      ones. A simple kinematic model of the ultrasound-driven interparticle fusion
      predicts a melting criterion that is nonmonotonically dependent on particle size
      and is shown to be in agreement with experiment.

PMID- 15506728
TI  - Chelation-assisted hydrative dimerization of 1-alkyne forming alpha,beta-enones
      by an Rh(I) catalyst.
AB  - The intermolecular hydrative dimerization of 1-alkyne was developed through the
      chelation-assisted catalytic system with Rh(I)/2-amino-3-picoline. This novel
      transformation afforded branched and linear alpha,beta-enones directly from two 1
      alkyne molecules and H2O. The results demonstrate that a branch/linear ratio can
      be controlled by the alkyl substituent of 1-alkyne.

PMID- 15506729
TI  - One-step preparation of highly monodisperse micron-size particles in organic
      solvents.
AB  - In this communication, we report the first simple and fast one-step method for
      synthesizing highly monodisperse micron-size PMMA particles in organic media
      through dispersion polymerization in the presence of PHSA (a polyhydroxyl-stearic
      acid graft PMMA copolymer) as a stabilizer. There are two significant advantages
      of our method over earlier methods. First, by optimizing the composition of a
      solvent mixture of hexane and dodecane, we were able to increase the
      concentration of monomer up to 50-56% and obtain unusually large (up to 10 mum in
      diameter) PMMA particles. Second, by strictly controlling the nucleation time, we
      were able to make PMMA particles with a low polydispersity of around 1%, much
      lower than has ever before been achieved for such large particles. We also report
      an unusual apparent metastable state in the nucleation stage.

PMID- 15506730
TI  - Complete selection of a self-assembling homo- or hetero-cavitand cage via metal
      coordination based on ligand tuning.
AB  - Selective formation of a homo- or hetero-cavitand cage via metal-coordination, by
      using tetra(4-pyridyl)-cavitand (1), tetrakis(4-pyridylethynyl)-cavitand (2), or
      tetrakis(4-cyanophenyl)-cavitand (3) as deep cavitand ligands and Pd(dppp)(OTf)2
      (4) as a connector, has been investigated by 1H NMR and CSI-MS. When the cavitand
      and 4 were mixed in CDCl3 in a 2:4 molar ratio, 1 gave a complicated mixture,
      whereas 2 or 3 formed a homo-cavitand cage {2(2).4[Pd(dppp)]}8+.8(TfO-) (5) or
      {2(3).4[Pd(dppp)]}8+.8(TfO-) (6), respectively, as a single species. In a 1:1:4
      mixture of 2, 3, and 4, homo-cavitand cages 5 and 6 were observed in a 1:1 ratio.
      In marked contrast, a mixture of 1, 3, and 4 in a 1:1:4 ratio was exclusively
      self-assembled into a hetero-cavitand cage {1.3.4[Pd(dppp)]}8+.8(TfO-) (7). The
      selectivity for the self-assembly of the homo- or hetero-cavitand cage via metal
      coordination would arise from a combination of factors such as coordination
      ability and steric demand of cavitand ligands.

PMID- 15506731
TI  - Synthesis of pyridinylpyrrole derivatives via the palladium-catalyzed reaction of
      acetylpyridines with methyleneaziridines.
AB  - The reaction of methyleneaziridines with o-, m-, and p-acetylpyridines proceeds
      very smoothly in the presence of a palladium catalyst, affording the biologically
      very important o-, m-, and p-pyridinylpyrrole derivatives in good to high yields.
      Not only ortho, meta, and para, but also related substrates, such as acetyl
      aromatics and hetarenes, can be used as the starting acetyl derivatives to
      synthesize related compounds to pyridinylpyrrole derivatives.

PMID- 15506732
TI  - Enantioselective construction of carbobicyclic scaffolds.
AB  - Allylic and benzylic Grignard reagents smoothly open phenylalkynyl-activated
      cyclic trisubstituted epoxides at the more substituted carbon atom to give
      secondary alcohols with a chiral quaternary center. These alcohols are good
      substrates for the construction of enantiomerically pure carbobicyclic scaffolds
      through intramolecular alkylation.

PMID- 15506733
TI  - Orientation-selected 15N-HYSCORE detection of weakly coupled nitrogens around the
      archaeal rieske [2Fe-2S] center.
AB  - The weakly coupled 15N atoms around a reduced Rieske [2Fe-2S] cluster of the
      uniformly 15N-labeled, hyperthermostable archaeal Rieske protein appear to
      produce readily observable cross-peaks in the HYSCORE spectra, with the well
      resolved couplings of 0.3-0.4 MHz for the Nepsilon and 1.1 MHz for the peptide
      backbone nitrogens, in addition to the contributions from the coordinated Ndelta
      atoms. These features can be used for structure-mechanism studies of the
      biological redox protein system involving the weakly coupled nitrogens in coupled
      electron-proton transfer reactions.

PMID- 15506734
TI  - Nickel-catalyzed arylcyanation of alkynes.
AB  - A nickel catalyst coordinated by trimethylphosphine is found to effect the
      addition reaction of Ar-CN bonds in aromatic nitriles across alkynes to give rise
      to various beta-arylalkenenitriles.

PMID- 15506735
TI  - Palladium-catalyzed synthesis of N-aryl-2-benzylindolines via tandem arylation of
      2-allylaniline: control of selectivity through in situ catalyst modification.
AB  - A new synthesis of N-aryl-2-benzylindolines from 2-allylanilines and two
      different aryl bromides is described. This transformation involves two different
      sequential metal-catalyzed reactions that lead to the formation of two C-N bonds
      and one C-C bond in a one-pot process. The selective installation of two
      different aryl groups in these reactions is accomplished by in situ modification
      of the palladium catalyst prior to addition of the second aryl bromide.

PMID- 15506736
TI  - Highly versatile organostibine mediators for living radical polymerization.
AB  - A new versatile method for conducting living radical polymerization has been
      developed in which organostibines induce consecutive group-transfer radical
      reactions with alkenes. The method has been successfully applied, for the first
      time, to the controlled polymerization of both conjugated and unconjugated vinyl
      monomers, and the desired polymers with predetermined molecular weight and low
      polydispersity index were obtained in excellent yields. This characteristic
      feature of this method is exemplified in the first synthesis of block copolymers
      composed of conjugated and unconjugated monomers, which would be of great
      importance as functional smart organic nanomaterials.

PMID- 15506737
TI  - Scandium half-metallocene-catalyzed syndiospecific styrene polymerization and
      styrene-ethylene copolymerization: unprecedented incorporation of syndiotactic
      styrene-styrene sequences in styrene-ethylene copolymers.
AB  - On treatment with 1 equiv of [Ph3C][B(C6F5)4], the scandium half-sandwich
      bis(alkyl) complex (C5Me4SiMe3)Sc(CH2SiMe3)2(THF) showed extremely high activity
      (up to 1.36 x 104 kg of sPS/(mol Sc.h)) and syndiospecificity (rrrr > 99%) for
      the polymerization of styrene at room temperature in toluene. More remarkably,
      this catalyst system could also effect the syndiospecific copolymerization of
      styrene with ethylene to yield styrene-ethylene copolymers having syndiotactic
      styrene-styrene sequences. The styrene content in the copolymers could be easily
      controlled by changing the styrene feed and could reach higher than 80 mol %.
      This is the first example of formation of such types of styrene-ethylene
      copolymers, which are expected to show novel properties.

PMID- 15506738
TI  - Origins of selectivities in proline-catalyzed alpha-aminoxylations.
AB  - The mechanisms, transition structures, regioselectivity, and stereoselectivity of
      proline-catalyzed alpha-aminoxylation reactions were studied with density
      functional theory (B3LYP/6-31G(d)). The most favorable transition structure
      involves the nucleophilic attack of the (E)-proline enamine to the oxygen of the
      nitrosobenzene with proton transfer from the carboxylic acid to the nitrogen.
      Enamine attack to the oxygen is favored over the attack on the nitrogen due to
      the greater basicity of the nitrogen. Previously proposed zwitterionic enaminium
      pathways are highly disfavored due to the energetic penalty associated with
      charge separations.

PMID- 15506740
TI  - Phosphaalkynes from acid chlorides via P for O(Cl) metathesis: a recyclable
      niobium phosphide (P(3-)) reagent that effects C-P triple-bond formation.
AB  - Reported herein is a new, metathetical P for O(Cl) exchange mediated by an
      anionic niobium phosphide complex that furnished phosphaalkynes (RCP) from acid
      chlorides (RC(O)Cl) under mild conditions. The niobaziridine hydride complex,
      Nb(H)(tBu(H)C=NAr)(N[Np]Ar)2 (1, Np = neopentyl, Ar = 3,5-Me2C6H3), has been
      shown previously to react with elemental phosphorus (P4), affording the mu
      diphosphide complex, (mu2:eta2,eta2-P2)[Nb(N[Np]Ar)3]2, (2), which can be
      subsequently reduced by sodium amalgam to the anonic, terminal phosphide complex,
      [Na][PNb(N[Np]Ar)3] (3). It is now shown that treatment of 3 with either pivaloyl
      (t-BuC(O)Cl) or 1-adamantoyl (1-AdC(O)Cl) chloride provides the thermally
      unstable niobacyles, (t-BuC(O)P)Nb(N[Np]Ar)3 (4-t-Bu) and (1-AdC(O)P)Nb(N[Np]Ar)3
      (4-1-Ad), which are intermediates along the pathway to ejection of the known
      phosphaalkynes t-BuCP (5-t-Bu) and 1-AdCP(5-1-Ad). Phosphaalkyne ejection from 4
      t-Bu and 4-1-Ad proceeds with formation of the niobium(V) oxo complex
      ONb(N[Np]Ar)3 (6) as a stable byproduct. Preliminary kinetic measurements for
      fragmentation of 4-t-Bu to 5-t-Bu and 6 in C6D6 solution are consistent with a
      first-order process, yielding the thermodynamic parameters DeltaH = 24.9 +/- 1.4
      kcal mol-1 and DeltaS = 2.4 +/- 4.3 cal mol-1 K-1 over the temperature range 308
      338 K. Separation of volatile 5-t-Bu from 6 after thermolysis has been readily
      achieved by vacuum transfer in yields of 90%. Pure 6 is recovered after vacuum
      transfer and can be treated with 1.0 equiv of triflic anhydride (Tf2O, Tf =
      O2SCF3) to afford the bistriflate complex, Nb(OTf)2(N[Np]Ar)3 (7), in high yield.
      Complex 7 provides direct access to 1 upon reduction with magnesium anthracene,
      thus completing a cycle of element activation, small-molecule generation via
      metathetical P-atom transfer, and deoxygenative recycling of the final niobium(V)
      oxo product.

PMID- 15506739
TI  - A designed protein interface that blocks fibril formation.
AB  - Protein fibril formation is implicated in many diseases, and therefore much
      effort has been focused toward the development of inhibitors of this process. In
      a previous project, a monomeric protein was computationally engineered to bind
      itself and form a heterodimer complex following interfacial redesign. One of the
      protein monomers, termed monomer-B, was unintentionally destabilized and shown to
      form macroscopic fibrils. Interestingly, in the presence of the designed binding
      partner, fibril formation was blocked. Here we describe the complete
      characterization of the amyloid properties of monomer-B and the inhibition of
      fiber formation by the designed binding partner, monomer-A. Both proteins are
      mutants of the betal domain of streptococcal protein-G. The free monomer-B
      protein forms amyloid-type fibrils, as determined by transmission electron
      microscopy and the change in fluorescence of Thioflavin T, an amyloid-specific
      dye. Fibril formation kinetics are influenced by pH, protein concentration, and
      seeding with preformed fibrils. Under all conditions tested, monomer-A was able
      to inhibit the formation of monomer-B fibrils. This inhibition is specific to the
      engineered interaction, as incubation of monomer-B with wild-type protein-G (a
      structural homologue) did not result in inhibition under the same conditions.
      Thus, this de novo-designed heterodimeric complex is an excellent model system
      for the study of protein-based fibril formation and inhibition. This system
      provides additional insight into the development of pharmaceuticals for amyloid
      disorders, as well as the potential use of amyloid fibrils for self-assembling
      nanostructures.

PMID- 15506741
TI  - Enantioselective synthesis of ansa-zirconocenes.
AB  - The reaction of the chiral chelated bis-amide complex Zr{(2R,4R)
      PhNCHMeCH2CHMeNPh}Cl2(THF)2 (R,R-7) with lithium ansa-bis-indenyl reagents
      Li2[SBI](Et2O) (8a, SBI = (1-indenyl)2SiMe2) or Li2[EBI](Et2O) (8b, EBI = 1,2-(1
      indenyl)2ethane) in THF affords the corresponding ansa-zirconocenes S,S
      (SBI)Zr{(2R,4R)-PhNCHMeCH2CHMeNPh} (S,S,R,R-9a) or S,S-(EBI)Zr{(2R,4R)
      PhNCHMeCH2CHMeNPh} (S,S,R,R-9b) in >95% isolated yield and >99% enantiomeric
      excess. Compound 9b was converted to the corresponding enantiomerically pure
      dichloride S,S-(EBI)ZrCl2 (S,S-10b) in 91% isolated yield by reaction with HCl in
      Et2O. The chiral diamine (2R,4R)-HPhNCHMeCH2CHMeNHPh (R,R-5) was recovered from
      this reaction.

PMID- 15506742
TI  - Reaction pathway of the [4 + 2] Diels-Alder adduct formation on Si(100)-2 x 1.
AB  - Despite a long history of experimental and theoretical investigation, the
      mechanism of the Diels-Alder (DA) reaction has been controversial since its
      discovery 80 years ago. From these investigations, two schools of thought have
      emerged, namely that the reaction can proceed via a concerted, symmetric or
      asymmetric mechanism or via a nonconcerted mechanism involving a zwitterion or
      diradical as an intermediate. Here, we employ finite temperature ab initio
      molecular dynamics simulations, employing forces computed "on the fly" from
      electronic structure calculations, to investigate the microscopic mechanism of DA
      adduct formation between 1,3-butadiene and the Si(100)-2x1 surface. Free energy
      profiles and nonequilibrium trajectories strongly suggest a nonconcerted
      mechanism that forms a zwitterionic intermediate state. This mechanism, which
      begins with a nucleophilic attack of the C=C double bond on the positive member
      of a charge-asymmetric buckled Si-Si dimer, was previously shown to be common to
      the formation of a wide range of adducts that can form on the surface.

PMID- 15506743
TI  - An yttrium ion-selective fluorescence sensor based on metal ion-controlled
      photoinduced electron transfer in zinc porphyrin-quinone dyad.
AB  - A highly Y3+-selective fluorescence sensor has been developed using zinc
      porphyrin-CONH-quinone dyad (ZnP-CONH-Q). The selective binding of the Q moiety
      of ZnP-CONH-Q with Y3+ retards electron transfer from the singlet excited state
      (1ZnP*) to Q, leading to a remarkable enhancement of the fluorescence intensity.

PMID- 15506744
TI  - DNA triangles and self-assembled hexagonal tilings.
AB  - We have designed and constructed DNA complexes in the form of triangles. We have
      created hexagonal planar tilings from these triangles via self-assembly. Unlike
      previously reported structures self-assembled from DNA, our structures appear to
      involve bending of double helices. Bending helices may be a useful design option
      in the creation of self-assembled DNA structures. It has been suggested that DNA
      self-assembly may lead to novel materials and efficient computational devices.

PMID- 15506745
TI  - Rare beryllium icosahedra in the intermediate valence compound CeBe13.
AB  - Single-crystal X-ray diffraction experiments show that the Be atoms in CeBe13
      form a Be12 icosahedra, which is a very unusual structural feature due, in part,
      to the remarkably low valence electron count of Be. Magnetization studies show
      that CeBe13 displays intermediate valence behavior, in which valence fluctuations
      between the Ce 4f0 and 4f1 states give rise to enhanced electronic specific heat
      and magnetic susceptibility. Calculations using ab initio theory were used to
      determine the electronic structure and bonding and to give insight into the
      relationship between the crystal structure, the bonding, and the intermediate
      valence behavior of CeBe13. The hybridization between the localized f electrons
      and the conduction electrons is responsible for the large values of the
      electronic specific heat coefficient (gamma approximately 100 mJ/mol K2) and
      magnetic susceptibility (chi approximately 1 x 10-3 emu/mol), which is in marked
      contrast to those of ordinary metals that have gamma approximately 1 mJ/mol K2
      and chi approximately 1 x 10-5 emu/mol values. The magnetic susceptibility, chi =
      M/H versus T, of a single crystal of CeBe13 exhibits a broad maximum at Tmax
      approximately 130 K and is typical of intermediate valence systems with an
      unusually large energy scale (Kondo), TK approximately 500 K.

PMID- 15506746
TI  - Lamination method for the study of interfaces in polymeric thin film transistors.
AB  - A method for the fabrication of polymeric thin-film transistors (TFTs) by
      lamination is described. Poly(dimethylsiloxane) stamps were used to delaminate
      thin films of semiconducting polymers from silicon wafers coated with a self
      assembled monolayer (SAM) formed from octyltrichlorosilane. These supported films
      were laminated onto electrode structures to form coplanar TFTs. The fabrication
      process was used to make TFTs with poly(3-hexylthiophene), P3HT, and poly[5,5'
      bis(3-dodecyl-2-thienyl)-2,2'-bithiophene], PQT-12. TFTs, where these polymers
      were laminated onto gate dielectrics coated with SAMs from octyltrichlorosilane,
      had effective field-effect mobilities of 0.03 and 0.005 cm2/(V s), respectively.
      TFTs where PQT-12 was laminated onto gate dielectrics that were not coated with a
      SAM also had mobility of 0.03 cm2/(V s). In contrast, TFTs fabricated by spin
      coating PQT-12 onto the same structure had mobilities ranging from 10-3 to 10-4
      cm2/(V s). These results suggest that the lower mobilities of polymer TFTs made
      with hydrophilic gate dielectrics are caused by molecular ordering in the
      semiconducting film rather than electronic effects of dipolar groups at the
      interface.

PMID- 15506747
TI  - Direct measurement of attractive van der Waals' forces between regenerated
      cellulose surfaces in an aqueous environment.
AB  - The interaction between cellulose surfaces is of fundamental interest in various
      natural and industrial systems. In this study, we describe the first direct
      measurements of an attractive van der Waals-type interaction between cellulose
      surfaces under aqueous conditions. An atomic force microscope, operating in
      colloidal probe mode, has been used to measure these interactions. The
      interaction between the cellulose surfaces is monotonically attractive at all
      surface separations. This long-range attractive interaction can be satisfactorily
      fitted with a Hamaker constant of 3.5 x 10-21 J.

PMID- 15506748
TI  - Photodissociation of heme distal methionine in ferrous cytochrome C revealed by
      subpicosecond time-resolved resonance Raman spectroscopy.
AB  - Cytochrome c (cyt c) is an electron-transfer heme protein that also binds nitric
      oxide (NO). In resting cyt c, two endogenous ligands of the heme iron are
      histidine-18 (His) and methionine-80 (Met) side chains, and NO binding requires
      the cleavage of one of the axial bonds. Previous femtosecond transient absorption
      studies suggested the photolysis of either Fe-His or Fe-Met bonds. We aimed at
      unequivocally identifying the internal side chain that is photodissociated in
      ferrous cyt c and at monitoring heme structural dynamics, by means of time
      resolved resonance Raman (TR3) spectroscopy with approximately 0.6 ps time
      resolution. The Fe-His stretching mode at 216 cm-1 has been observed in
      photoproduct TR3 spectra for the first time for a c-type heme. The same transient
      mode was observed for a model ferrous cyt c N-fragment (residues 1-56) ligated
      with two His in the resting state. Our TR3 data reveal that upon ferrous cyt c
      photoexcitation, (i) distal Met side chain is instantly released, producing a
      five-coordinated domed heme structure, (ii) proximal His side chain, coupled to
      the heme, exhibits distortion due to strain exerted by the protein, and (iii)
      alteration in heme-cysteine coupling takes place along with the relaxation of the
      protein-induced deformations of the heme macrocycle.

PMID- 15506749
TI  - Modulation of the folding energy landscape of cytochrome C with salt.
AB  - The folding reaction of acid-unfolded cytochrome c in the presence of various
      amounts of KCl was investigated with Trp fluorescence and resonance Raman
      spectroscopies. It was found that the too-early-too-much polypeptide chain
      collapse induced by KCl yields some stable folding intermediates, which need to
      overcome a higher energy barrier to fold into their native conformation. We
      propose that the charge distribution on the polypeptide chain is part of the
      folding codon encoded in the linear amino acid sequence. The charge screening
      effect introduced by KCl alters the shape of the energy landscape by raising the
      slope of the upper rim and introduces a rugged energy surface toward the bottom
      of the folding funnel.

PMID- 15506750
TI  - A new convergent strategy for the synthesis of calixarenes via a triple
      annulation of Fischer carbene complexes.
AB  - A new method for the synthesis of unsymmetrical calix[4]arenes is described which
      involves the reaction of a diyne with a bis-carbene complex of chromium. This
      synthesis of calixarenes is unique in that it involves the formation of two of
      the four benzene rings of the calixarene and the macrocyclic ring of the
      calixarene in the same step. Thus, two of the four benzene rings of the
      calixarene are identical, but the other two rings may each be different, giving a
      general method for the synthesis of calixarenes in which there are either two or
      three differently substituted benzene rings. This protocol gives access to a
      large family of unsymmetrical calixarenes by the proper choice of arene
      substitution in the starting diyne and the starting carbene complex. Nine
      examples are presented in which the yields in the key triple annulation step
      range from 22 to 41%. The overall yields of calixarenes from commercially
      available starting materials compare favorably with those from existing methods
      for the synthesis of unsymmetrical calix[4]arenes.

PMID- 15506751
TI  - Fulvenes, fulvalenes, and azulene: are they aromatic chameleons?
AB  - On the basis of the theory of Baird on reversal of Huckel's rule for aromaticity
      and antiaromaticity of annulenes when going from the electronic ground state (S0)
      to the lowest pipi* triplet state (T1) (J. Am. Chem. Soc. 1972, 94, 4941), we
      argue that fulvenes, fulvalenes, and azulene are "aromatic chameleons". The
      dipole moments of fulvenes in T1 should be of comparable magnitude to those of
      S0, but due to the reversal of Huckel's aromaticity rule in T1, their dipole
      should be in the opposite direction. Thereby, they are capable of adopting some
      aromaticity in both the T1 and S0 states as they adapt their dipolar resonance
      structures. The same applies to fulvalenes and azulene in their lowest quintet
      states (Q1) when compared to S0. Our hypothesis on chameleon behavior is
      supported by quantum chemical OLYP, CASSCF, and CASPT2 calculations of dipole
      moments, pi-orbital populations, and energies.

PMID- 15506752
TI  - Metalloform-selective inhibitors of escherichia coli methionine aminopeptidase
      and X-ray structure of a Mn(II)-form enzyme complexed with an inhibitor.
AB  - Methionine aminopeptidase (MetAP) enzymes require a divalent metal ion such as
      Mn(II), Fe(II), Co(II), Ni(II), or Zn(II) for its removal of the N-terminal
      methionine from newly synthesized proteins, but it is not certain which of these
      ions is most important in vivo. Metalloform-selective MetAP inhibitors could be
      valuable for defining which metals are physiologically relevant for MetAP
      activation and could serve as leads for development of new therapeutic agents. We
      have screened a library of 43 736 small drug-like molecules against Escherichia
      coli MetAP and identified two groups of potent and highly metalloform-selective
      inhibitors of the Co(II)-form, and of the Mn(II)-form, of this enzyme. Compound 1
      is 790-fold more selective for the Co(II)-form, while compound 4 is over 640-fold
      more potent toward the Mn(II)-form. The X-ray structure of a di-Mn(II) form of E.
      coli MetAP complexed with the Mn(II)-form-selective compound 4 was obtained, and
      it shows that the inhibitor interacts with both Mn(II) ions through the two
      oxygen atoms of its free carboxylate group. The preferential coordination of the
      hard (oxygen) donors to Mn(II) may contribute to its superb selectivity toward
      the Mn(II)-form.

PMID- 15506753
TI  - Synthetic stitching with silicon: geminal alkylation-hydroxylation of alkynyl
      carbonyl compounds.
AB  - A new strategy for the synthesis of beta-carbonyl-substituted tertiary alcohols
      from alpha,beta-alkynyl ketones and esters has been demonstrated. A silicon
      tether is used to internally deliver an alkyl group, which, combined with a C-Si
      to C-O transformation, can regio- and diastereoselectively "stitch" together
      geminal C-C and C-O bonds at the beta-position of an electron-withdrawing group.
      Regioselective alkyne hydrosilylation by a trans addition process provides clean
      access to trisubstituted vinylsilanes. Subsequent one-pot fluoride-induced C-C
      bond formation and oxidation of the resulting tertiary silane, a type of silane
      not normally reactive to such conditions, affords the desired products. The
      utility of neighboring ketone and carboxylate groups in promoting the oxidation
      of these highly hindered tertiary alcohols, an observation that may affect
      synthetic design of routes depending on such oxidations, is demonstrated. Good
      diastereoselection (>10:1) is observed for substrates bearing gamma-alkoxy
      stereocenters.

PMID- 15506754
TI  - X-ray crystal structure of the acylated beta-lactam sensor domain of BlaR1 from
      Staphylococcus aureus and the mechanism of receptor activation for signal
      transduction.
AB  - Methicillin-resistant strains of Staphylococcus aureus (MRSA) are the major cause
      of infections worldwide. Transcription of the beta-lactamase and PBP2a resistance
      genes is mediated by two closely related signal-transducing integral membrane
      proteins, BlaR1 and MecR1, upon binding of the beta-lactam inducer to the sensor
      domain. Herein we report the crystal structure at 1.75 A resolution of the sensor
      domain of BlaR1 in complex with a cephalosporin antibiotic. Activation of the
      signal transducer involves acylation of serine 389 by the beta-lactam antibiotic,
      a process promoted by the N-carboxylated side chain of Lys392. We present
      evidence that, on acylation, the lysine side chain experiences a spontaneous
      decarboxylation that entraps the sensor in its activated state. Kinetic
      determinations and quantum mechanical/molecular mechanical calculations and the
      interaction networks in the crystal structure shed light on how this
      unprecedented process for activation of a receptor may be achieved and provide
      insights into the mechanistic features that differentiate the signal-transducing
      receptor from the structurally related class D beta-lactamases, enzymes of
      antibiotic resistance.

PMID- 15506755
TI  - Characterization of protein-ligand interactions by high-resolution solid-state
      NMR spectroscopy.
AB  - A novel approach for detection of ligand binding to a protein in solid samples is
      described. Hydrated precipitates of the anti-apoptotic protein Bcl-xL show well
      resolved (13)C-(13)C 2D solid-state NMR spectra that allow site-specific
      assignment of resonances for many residues in uniformly (13)C-enriched samples.
      Binding of a small peptide or drug-like organic molecule leads to changes in the
      chemical shift of resonances from multiple residues in the protein that can be
      monitored to characterize binding. Differential chemical shifts can be used to
      distinguish between direct protein-ligand contacts and small conformational
      changes of the protein induced by ligand binding. The agreement with prior
      solution-state NMR results indicates that the binding pocket in solid and liquid
      samples is similar for this protein. Advantages of different labeling schemes
      involving selective (13)C enrichment of methyl groups of Ala, Val, Leu, and Ile
      (Cdelta1) for characterizing protein-ligand interactions are also discussed. It
      is demonstrated that high-resolution solid-state NMR spectroscopy on uniformly or
      extensively (13)C-enriched samples has the potential to screen proteins of
      moderate size ( approximately 20 kDa) for ligand binding as hydrated solids. The
      results presented here suggest the possibility of using solid-state NMR to study
      ligand binding in proteins not amenable to solution NMR.

PMID- 15506756
TI  - Mimicking protein-protein electron transfer: voltammetry of Pseudomonas
      aeruginosa azurin and the Thermus thermophilus Cu(A) domain at omega-derivatized
      self-assembled-monolayer gold electrodes.
AB  - Well-defined voltammetric responses of redox proteins with acidic-to-neutral pI
      values have been obtained on pure alkanethiol as well as on mixed self-assembled
      monolayer (SAM) omega-derivatized alkanethiol/gold bead electrodes. Both azurin
      (P. aeruginosa) (pI = 5.6) and subunit II (Cu(A) domain) of ba(3)-type cytochrome
      c oxidase (T. thermophilus) (pI = 6.0) exhibit optimal voltammetric responses on
      1:1 mixtures of [H(3)C(CH(2))(n)()SH + HO(CH(2))(n)()SH] SAMs. The electron
      transfer (ET) rate vs distance behavior of azurin and Cu(A) is independent of the
      omega-derivatized alkanethiol SAM headgroups. Strikingly, only wild-type azurin
      and mutants containing Trp48 give voltammetric responses: based on modeling, we
      suggest that electronic coupling with the SAM headgroup (H(3)C- and/or HO-)
      occurs at the Asn47 side chain carbonyl oxygen and that an Asn47-Cys112 hydrogen
      bond promotes intramolecular ET to the copper. Inspection of models also
      indicates that the Cu(A) domain of ba(3)-type cytochrome c oxidase is coupled to
      the SAM headgroup (H(3)C- and/or HO-) near the main chain carbonyl oxygen of
      Cys153 and that Phe88 (analogous to Trp143 in subunit II of cytochrome c oxidase
      from R. sphaeroides) is not involved in the dominant tunneling pathway. Our work
      suggests that hydrogen bonds from hydroxyl or other proton-donor groups to
      carbonyl oxygens potentially can facilitate intermolecular ET between
      physiological redox partners.

PMID- 15506757
TI  - Direct photochemical patterning and refunctionalization of supported phospholipid
      bilayers.
AB  - A wet photolithographic route for micropatterning fluid phospholipid bilayers is
      demonstrated in which spatially directed illumination by short-wavelength
      ultraviolet radiation results in highly localized photochemical degradation of
      the exposed lipids. Using this method, we can directly engineer patterns of
      hydrophilic voids within a fluid membrane as well as isolated membrane corrals
      over large substrate areas. We show that the lipid-free regions can be refilled
      by the same or other lipids and lipid mixtures which establish contiguity with
      the existing membrane, thereby providing a synthetic means for manipulating
      membrane compositions, engineering metastable membrane microdomains, probing 2D
      lipid-lipid mixing, and designing membrane-embedded arrays of soluble proteins.
      Following this route, new constructs can be envisaged for high-throughput
      membrane proteomic, biosensor array, and spatially directed, aqueous-phase
      material synthesis.

PMID- 15506758
TI  - Binol quinone methides as bisalkylating and DNA cross-linking agents.
AB  - The photogeneration and detection of new binol quinone methides undergoing mono-
      and bisalkylation of free nucleophiles was investigated by product distribution
      analysis and laser flash photolysis in water solution using binol quaternary
      ammonium derivatives 2 and 12 as photoactivated precursors. The alkylation
      processes of N and S nucleophiles are strongly competitive with the hydration
      reaction. DNA cross-linking potency of the water-soluble binol quaternary
      ammonium salt 2 was investigated as a pH function and compared to that of other
      quaternary ammonium salts capable of benzo-QM (QM = quinone methide)
      photogeneration by gel electrophoresis. DFT calculations in the gas phase and in
      water bulk on the binol and benzo quaternary ammonium salts 2 and 4 evidence
      structural and electrostatic features of the binol derivative which might offer a
      rationalization of its promising high photo-cross-linking efficiency.

PMID- 15506759
TI  - Destabilizing universal linkers for signal amplification in self-ligating probes
      for RNA.
AB  - Recent studies have established the utility of oligonucleotide ligation methods
      in the detection of DNAs and RNAs in solution and in cellular imaging. Notably,
      the ligated full-length oligonucleotide products commonly bind to the target
      nucleic acid much more tightly than do the two starting half-probes, which
      effectively limits the resulting signals to one per target. Here, we report on a
      molecular strategy for destabilizing ligated products in template-promoted self
      ligation reactions, thus yielding multiple signals per target. A new universal
      linker design is described in which a dabsyl leaving group is placed on a short
      alkane tether. This allows the placement of an electrophile at the end of any DNA
      sequence, in contrast to earlier ligation strategies, and it also speeds reaction
      rates by a factor of 4-5. This new class of molecular linker/activator yields as
      much as 92-fold amplification of signals in DNA and RNA detection, and proceeds
      without enzymes, added reagents, or thermal cycling. The linker is shown to
      destabilize the ligation product without destabilizing the transition state for
      ligation. This lowers product inhibition, and the target DNA or RNA thus becomes
      a catalyst for isothermally generating multiple signals for its detection. This
      enhanced signal generation is demonstrated in solution experiments and in solid
      supported assays.

PMID- 15506760
TI  - Tunable reactivation of nanoparticle-inhibited beta-galactosidase by glutathione
      at intracellular concentrations.
AB  - Positively charged trimethylammonium-functionalized mixed monolayer protected
      clusters (MMPCs) of different chain lengths (C(8) and C(11)) have been used to
      bind beta-galactosidase through complementary electrostatic interactions,
      resulting in complete enzyme inhibition. This inhibition can be reversed in vitro
      by intracellular concentrations of glutathione (GSH), the main thiol component of
      the cell. The restoration of activity depends on the chain length of the
      monolayer. The activity of enzyme bound to particles with C(8) monolayer was
      completely restored by intracellular concentrations (1-10 mM) of GSH; however,
      little or no release was observed at extracellular GSH concentrations. In
      contrast, no restoration was observed for enzyme bound to the C(11) particles at
      any of the concentrations studied. Taken together, these studies demonstrate that
      the GSH-mediated release of enzymes bound to MMPCs can be tuned through the
      structure of the monolayer, a significant tool for protein and drug delivery
      applications.

PMID- 15506761
TI  - Rupture force between the third strand and the double strand within a triplex
      DNA.
AB  - The rupture force to separate the third strand and the duplex within a triplex
      DNA was measured by means of atomic force spectroscopy. The tip and the sample
      surfaces were functionalized by oligodeoxyribonucleotides 5'
      TTCTTCTTTCTTTTCCTTTTCTTTCTTCTTACTTCTCTCTCTC TCTCTCT-SH-3'. The sample surface was
      hybridized with 5'-AAGAAGAAAGAAAAGGAAAAGAAAGAAGAA-3' to form a double strand DNA
      on the surface prior to the force measurements. These sequences form triple
      helices with 30 base pairs under a pH of 5.8 and in the presence of 2.0 mM
      spermine. Signals of rupture of single and multiple triplex DNA were observed in
      the force distance curves. Rupture force histograms revealed a force of 42.6 +/-
      1.9 pN from 24 independent measurements at a tip velocity of 400 nm/s to separate
      the third strand from duplex DNA. The velocity dependence of the rupture force
      quantum indicates a thermal dissociation process similar to that of rupturing a
      ds-DNA. The number of rupture events was controlled by adding oligonucleotides 5'
      AAGAAGAAAGAAAAGGAAAAGAAAGAAGAA-3' either to reduce or to initiate triplex
      formation.

PMID- 15506762
TI  - A chemoenzymatic approach to glycopeptide antibiotics.
AB  - Many biologically active natural products are constrained by macrocyclization and
      modified with carbohydrates. These two types of modifications are essential for
      their biological activities. Here we report a chemoenzymatic approach to make
      carbohydrate-modified cyclic peptide antibiotics. Using a thioesterase domain
      from the decapeptide tyrocidine synthetase, 13 head-to-tail cyclized tyrocidine
      derivatives were obtained with one to three propargylglycines incorporated at
      positions 3-8. These cyclic peptides were then conjugated to 21 azido sugars via
      copper(I)-catalyzed cycloaddition. Antibacterial and hemolytic assays showed that
      the two best glycopeptides, Tyc4PG-14 and Tyc4PG-15, have a 6-fold better
      therapeutic index than the natural tyrocidine. We believe this method will also
      be useful for modifying other natural products to search for new therapeutics.

PMID- 15506763
TI  - Domain-specific incorporation of noninvasive optical probes into recombinant
      proteins.
AB  - An integrated approach is described that allows the domain-specific incorporation
      of optical probes into large recombinant proteins. The strategy is the
      combination of two existing techniques, expressed protein ligation (EPL) and in
      vivo amino acid replacement of tryptophans with tryptophan (Trp) analogues. The
      Src homology 3 (SH3) domain from the c-Crk-I adaptor protein has been labeled
      with a Trp analogue, 7-azatryptophan (7AW), using Escherichia coli Trp
      auxotrophs. Structural, biochemical, and thermodynamic studies show that
      incorporation of 7AW does not significantly perturb the structure or function of
      the isolated domain. Ligation of the 7AW-labeled SH3 domain to the c-Crk-I Src
      homology 2 (SH2) domain, via EPL, generated the multidomain protein, c-Crk-I,
      with a domain-specific label. Studies of this labeled protein show that the
      biochemical and thermodynamic properties of the SH3 domain do not change within
      the context of a larger multidomain protein. The technology described here is
      likely to be a useful tool in enhancing our understanding of the behavior of
      modular domains in their natural context, within multidomain proteins.

PMID- 15506765
TI  - Two-metal ion, Ni(II) and Cu(II), binding alpha-helical coiled coil peptide.
AB  - Metalloproteins are an attractive target for de novo design. Usually, natural
      proteins incorporate two or more (hetero- or homo-) metal ions into their
      frameworks to perform their functions, but the design of multiple metal-binding
      sites is usually difficult to achieve. Here, we undertook the de novo engineering
      of heterometal-binding sites, Ni(II) and Cu(II), into a designed coiled coil
      structure based on an isoleucine zipper (IZ) peptide. Previously, we described
      two peptides, IZ-3adH and IZ-3aH. The former has two His residues and forms a
      triple-stranded coiled coil after binding Ni(II), Zn(II), or Cu(II). The latter
      has one His residue, which allowed binding with Cu(II) and Zn(II), but not with
      Ni(II). On the basis of these properties, we newly designed IZ(5)-2a3adH as a
      heterometal-binding peptide. This peptide can bind Cu(II) and Ni(II)
      simultaneously in the hydrophobic core of the triple-stranded coiled coil. The
      first metal ion binding induced the folding of the peptide into the triple
      stranded coiled coil, thereby promoting the second metal ion binding. This is the
      first example of a peptide that can bind two different metal ions. This
      construction should provide valuable insights for the de novo design of
      metalloproteins.

PMID- 15506764
TI  - Glycoinsulins: dendritic sialyloligosaccharide-displaying insulins showing a
      prolonged blood-sugar-lowering activity.
AB  - Mono-, di-, and trisialyloligosaccharides were introduced to mutant insulins
      through enzymatic reactions. Sugar chains were sialylated by alpha2,6
      sialyltransferase (alpha2,6-SiaT) via an accessible glutamine residue at the N
      terminus of the B-chain attached by transglutaminase (TGase). Sia2,6-di-LacNAc
      Ins(B-F1Q) and Sia2,6-tri-LacNAc-Ins(B-F1Q), displaying two and three sialyl-N
      acetyllactosamines, respectively, were administered to hyperglycemic mice. Both
      branched glycoinsulins showed prolonged glucose-lowering effects compared to
      native or lactose-carrying insulins, showing that sialic acid is important in
      obtaining a prolonged effect. Sia2,6-tri-LacNAc-Ins(B-F1Q), in particular,
      induced a significant delay in the recovery of glucose levels.

PMID- 15506766
TI  - A method for solid-phase synthesis of oligonucleotide 5'-peptide-conjugates using
      acid-labile alpha-amino protections.
AB  - We describe the development of a solid-phase technique for the synthesis of 5'
      peptide-oligonucleotide conjugates (POCs) with a uniform protection strategy for
      the nucleic acid and the peptide fragments. On the alpha-amino function, the
      amino acid building blocks were protected with the 2-(biphenyl-4-yl)propan-2
      yloxycarbonyl (Bpoc) group. This protection is removed during the stepwise
      peptide elongation by the same acidic conditions used for removal of the
      dimethoxytrityl (DMT) group used in the oligonucleotide assembly (3%
      trichloroacetic acid, 2 min). The 2-(3,5-dimethoxyphenyl)propan-2-yloxycarbonyl
      (Ddz) group was also tested. With this somewhat more stable group, a prolonged
      contact with the acid (at least 16 min) was required for accomplishing complete
      alpha-amino deprotection, which resulted in some degree of depurination of the
      acid-sensitive DNA chain. Base-labile acyl protections were adopted for the side
      chains of histidine, lysine, and the nucleobase amino functions. These were all
      removed in the final deblocking step by ammonolysis. This uniform protection
      scheme for the peptide and the oligonucleotide enabled the total stepwise
      synthesis of model conjugates in the 3' --> N direction with high efficiency and
      purity.

PMID- 15506767
TI  - NMR structural analysis of a modular threading tetraintercalator bound to DNA.
AB  - The synthesis and NMR structural studies are reported for a modular threading
      tetraintercalator bound to DNA. The tetraintercalator design is based on 1,4,5,8
      tetracarboxylic naphthalene diimide units connected through flexible peptide
      linkers. Aided by an overall C(2) symmetry, NMR analysis verified a threading
      polyintercalation mode of binding, with linkers alternating in the order minor
      groove, major groove, minor groove, analogous to how a snake might climb a
      ladder. This study represents the first NMR analysis of a threading
      tetraintercalator and, as such, structurally characterizes a new topology for
      molecules that bind to relatively long DNA sequences with extensive access to
      both DNA grooves.

PMID- 15506768
TI  - Asymmetric synthesis of pyrrolidinoindolines. Application for the practical total
      synthesis of (-)-phenserine.
AB  - A versatile route to enantiopure 3,3-disubstituted oxindoles and 3a-substituted
      pyrrolidinoindolines is described in which diastereoselective dialkylation of
      enantiopure ditriflate 10 with oxindole enolates is the central step. These
      reactions are rare examples of alkylations of prostereogenic enolates with chiral
      sp(3) electrophiles that proceed with high facial selectivity (10-20:1). The
      scope of this method is explored, and a model to rationalize the sense of
      stereoselection is advanced. This dialkylation chemistry was used to synthesize (
      )-phenserine on a multigram scale in six steps and 43% overall yield from 5
      methoxy-1,3-dimethyloxindole (27) and to complete a short formal total synthesis
      of (-)-physostigmine (2).

PMID- 15506769
TI  - Structural characterization of modular supramolecular architectures in solution.
AB  - Structures of modular supramolecular architectures consisting of a hexameric,
      diphenylethyne-linked porphyrin macrocyclic array and the corresponding host
      guest complex formed by inclusion of a tripyridyl guest molecule were
      characterized in solution using high-angle X-ray scattering. Scattering
      measurements made to 6 A resolution coupled with pair distance function (PDF)
      analyses demonstrated that (1) the porphyrin architectures are not rigid but are
      distributed across a conformational ensemble with a mean diameter that is 1.5 A
      shorter than the diameter of a symmetric, energy-minimized model structure, (2)
      the conformational envelope has limits of 3 A positional dispersion and full
      rotational freedom for all six porphyrin groups, and (3) insertion of the
      tripyridyl guest molecule expands the diameter of the host conformer by 0.6 A and
      decreases the configurational dispersion by approximately 2-fold. These results
      validate the molecular design, provide a new measure of conformational ensembles
      in solution that cannot be obtained by other techniques, and establish a
      structural basis for understanding the photophysical and guest-hosting functions
      of the hexameric porphyrin architectures in liquids.

PMID- 15506770
TI  - Guest shape-responsive fitting of porous coordination polymer with shrinkable
      framework.
AB  - In situ synchrotron X-ray powder diffraction patterns of porous coordination
      polymers [[Cu(2)(pzdc)(2)(bpy)].G] have been measured (pzdc = pyrazine-2,3
      dicarboxylate, bpy = 4,4'-bipyridine) (where G = H(2)O for CPL-2 superset
      H(2)()O, G = benzene for CPL-2 superset benzene, and G = void for the apohost).
      The structures of apohost and CPL-2 superset benzene were determined from
      Rietveld analysis. Adsorption of benzene in the channels induced a remarkable
      contraction in the crystal (b axis; 6.8%, volume; 4.9%), although the channels
      were occupied by the benzene molecules. This crystal transformation provides a
      new pore structure that is well suited for benzene molecules, and we denote it as
      a "shape-responsive fitting" transformation. This type of pore gives rise to a
      new guideline: frameworks can be composed of flexible motifs that are linked via
      strong bond and/or stiff motifs that are connected via weaker bonds.

PMID- 15506771
TI  - Barrierless electron transfer bond fragmentation reactions.
AB  - The ultrafast N-O bond fragmentation in a series of N-methoxypyridyl radicals,
      formed by one-electron reduction of the corresponding N-methoxypyridiniums, has
      been investigated as potentially barrierless electron-transfer-initiated chemical
      reactions. A model for the reaction involving the electronic and geometric
      factors that control the shape of the potential energy surface for the reaction
      is described. On the basis of this model, molecular structural features
      appropriate for ultrafast reactivity are proposed. Femtosecond kinetic
      measurements on these reactions are consistent with a kinetic definition of an
      essentially barrierless reaction, i.e., that the lifetime of the radical is a few
      vibrational periods of the fragmenting bond, for the p-methoxy-N-methoxypyridyl
      radical.

PMID- 15506772
TI  - Rational principles for modulating fluorescence properties of fluorescein.
AB  - Rational design strategies based on practical fluorescence modulation mechanisms
      would enable us to rapidly develop novel fluorescence probes for target
      molecules. Here, we present a practical and general principle for modulating the
      fluorescence properties of fluorescein. We hypothesized that (a) the fluorescein
      molecule can be divided into two moieties, i.e., the xanthene moiety as a
      fluorophore and the benzene moiety as a fluorescence-controlling moiety, even
      though there is no obvious linker structure between them, and (b) the
      fluorescence properties can be modulated via a photoinduced electron transfer
      (PeT) process from the excited fluorophore to a reducible benzene moiety (donor
      excited PeT; d-PeT). To evaluate the relationship between the reduction potential
      of the benzene moiety and the fluorescence properties, we designed and
      synthesized various derivatives in which the reduction potential of the benzene
      moiety was fine tuned by introducing electron-withdrawing groups onto the benzene
      moiety. Our results clearly show that the fluorescence properties of fluorescein
      derivatives were indeed finely modulated depending upon the reduction potential
      of the benzene moiety. This information provides a basis for a practical strategy
      for rational design of novel functional fluorescence probes.

PMID- 15506773
TI  - Nanosecond redox equilibrium method for determining oxidation potentials in
      organic media.
AB  - A general, nanosecond equilibrium method is described for determining
      thermodynamically meaningful oxidation potentials in organic media for compounds
      that form highly reactive cation radicals upon one-electron oxidation. The method
      provides oxidation potentials with unusually high precision and accuracy. Redox
      ladders have been constructed of appropriate reference compounds in
      dichloromethane and in acetonitrile that can be used to set up electron-transfer
      equilibria with compounds with unknown oxidation potentials. The method has been
      successfully applied to determining equilibrium oxidation potentials for a series
      of aryl-alkylcyclopropanes, whose oxidation potentials were imprecisely known
      previously. Structure-property trends for oxidation potentials of the
      cyclopropanes are discussed.

PMID- 15506774
TI  - A synthesis strategy yielding skeletally diverse small molecules combinatorially.
AB  - The efficient synthesis of small molecules having many molecular skeletons is an
      unsolved problem in diversity-oriented synthesis (DOS). We describe the
      development and application of a synthesis strategy that uses common reaction
      conditions to transform a collection of similar substrates into a collection of
      products having distinct molecular skeletons. The substrates have different
      appendages that pre-encode skeletal information, called sigma-elements. This
      approach is analogous to the natural process of protein folding in which
      different primary sequences of amino acids are transformed into macromolecules
      having distinct three-dimensional structures under common folding conditions.
      Like sigma-elements, the amino acid sequences pre-encode structural information.
      An advantage of using folding processes to generate skeletal diversity in DOS is
      that skeletal information can be pre-encoded into substrates in a combinatorial
      fashion, similar to the way protein structural information is pre-encoded
      combinatorially in polypeptide sequences, thus making it possible to generate
      skeletal diversity in an efficient manner. This efficiency was realized in the
      context of a fully encoded, split-pool synthesis of approximately 1260 compounds
      potentially representing all possible combinations of building block,
      stereochemical, and skeletal diversity elements.

PMID- 15506775
TI  - Pentadienyls vs cyclopentadienyls and reversal of metal-ligand bonding affinity
      with metal oxidation state: synthesis, molecular structures, and electronic
      structures of high-valent zirconium pentadienyl complexes.
AB  - Molecules of the form Cp(6,6-dmch)ZrX(2) (Cp = eta(5)-cyclopentadienyl, X = Cl,
      Br, I; 6,6-dmch = eta(5)-6,6-dimethylcyclohexadienyl) have been synthesized, and
      the molecular and electronic structures have been investigated. These molecules
      allow direct comparison of the bonding and properties of pentadienyl and
      cyclopentadienyl ligands in the same high-oxidation-state metal complexes. Unlike
      the well-known Cp(2)ZrX(2) analogues, these Cp(6,6-dmch)ZrX(2) molecules are
      intensely colored, indicating significantly different relative energies of the
      frontier orbitals. Also unusual, the average Zr-C distances to the 6,6-dmch
      pentadienyl ligand are about 0.1 A longer than the average Zr-C distances to the
      cyclopentadienyl ligand for these Zr(IV) complexes, opposite of what is observed
      for the Zr(II) complex Cp(2,6,6-tmch)Zr(PMe(3))(2) (tmch = eta(5)-2,6,6
      trimethylcyclohexadienyl), reflecting a dramatic reversal in the favorability of
      the bonding depending on the metal oxidation state. The experimental and
      computational results indicate that the color of the Cp(6,6-dmch)ZrX(2) complexes
      is due to a 6,6-dmch ligand-to-metal charge-transfer band. Compared to the
      Cp(2)ZrX(2) analogues, the Cp(6,6-dmch)ZrX(2) molecules have a considerably less
      stable HOMO that is pentadienyl-based and an essentially unchanged metal-based
      LUMO. Also, the lowest unoccupied orbital of pentadienyl is stabilized relative
      to cyclopentadienyl and becomes a better potential delta electron acceptor, thus
      contributing to the differences in structure and reactivity of the low-valent and
      high-valent metal complexes.

PMID- 15506776
TI  - Self-assembled polymer membrane capsules inflated by osmotic pressure.
AB  - We fabricate and characterize capsules that are composite membranes, made of a
      polymer network stabilized by adsorption to colloids and inflated by osmotic
      pressure from internal free polyelectrolyte; here, poly-l-lysine forms the
      network and inflates the capsules. To assess these capsules' properties and
      structure, we deform capsules using microcantilevers and use finite element
      modeling to describe these deformations. Additional experimental tests confirm
      the model's validity. These capsules' resilient response to mechanical forces
      indicates that loading and shear should be good triggers for the release of
      contents via deformation. The osmotic pressure inflating these capsules has the
      potential to trigger release of contents via deflation in response to changes in
      the capsules' environment; we demonstrate addition of salt as a trigger for
      deflating capsules. Because these capsules have a variety of release triggers
      available and the technique used to fabricate them is very flexible and allows
      high encapsulation efficiency, these capsules have very high potential for
      application in many areas.

PMID- 15506777
TI  - Covalently bonded 1(infinity)[Pt]- chains in BaPt: extension of the Zintl-Klemm
      concept to anionic transition metals?
AB  - BaPt has been synthesized by reaction of a 1:1 mixture of Ba and Pt at 1223 K in
      argon and characterized by single-crystal X-ray structure determination and
      electrical resistivity and magnetic susceptibility measurements. The compound
      crystallizes in the NiAs structure type with an extremely low value for the c/a
      ratio (hexagonal space group P6(3)/mmc with a = 5.057(2) A, c = 5.420(3) A, c/a =
      1.072, R1 = 0.0297, N(hkl)() = 93). This c/a ratio reflects structural features
      that are unusual for the NiAs type: Pt is coordinated linearly by two other Pt
      atoms at a distance as short as 2.71 A, thus forming a chain along [001] of
      homonuclearly bonded platinum. Band structure calculations and electron
      localization function analyses reveal a covalent character of Pt-Pt interactions
      along the c axis and two-dimensional metallic conductivity parallel to the ab
      plane. In terms of the Zintl-Klemm concept, in its most general sense, BaPt can
      be formulated as (Ba(2+)(1(infinity)[Pt]-) x e-), and it can be considered a new
      example of platinide anions in the solid state.

PMID- 15506778
TI  - Accelerated luminophore discovery through combinatorial synthesis.
AB  - A method for accelerating the discovery of ionic luminophores using combinatorial
      techniques is reported. The photophysical properties of the resulting transition
      metal-based chromophores were compared against a series of analogous,
      traditionally prepared species. The strong overlap between these two sets
      confirms the identity of the parallel synthesis products and supports the
      truthfulness of the combinatorial results. Further support for the combinatorial
      method comes from the adherence of these complexes to the energy gap law. The
      relationship between the structure of a complex and its photophysical properties
      was also considered, and static DFT calculations were used to assess whether it
      is feasible to predict the luminescent behavior of novel materials.

PMID- 15506779
TI  - Five-coordinate Fe(III)NO and Fe(II)CO porphyrinates: where are the electrons and
      why does it matter?
AB  - Recent years have seen dramatic growth in our understanding of the biological
      roles of nitric oxide (NO). Yet, the fundamental underpinnings of its
      reactivities with transition metal centers in proteins and enzymes, the
      stabilities of their structures, and the relationships between structure and
      reactivity remains, to a significant extent, elusive. This is especially true for
      the so-called ferric heme nitrosyls ([FeNO](6) in the Enemark-Feltham scheme).
      The Fe-CO and C-O bond strengths in the isoelectronic ferrous carbonyl complexes
      are widely recognized to be inversely correlated and sensitive to structural,
      environmental, and electronic factors. On the other hand, the Fe-NO and N-O bonds
      in [FeNO](6) heme complexes exhibit seemingly inconsistent behavior in response
      to varying structure and environment. This report contains resonance Raman and
      density functional theory results that suggest a new model for FeNO bonding in
      five-coordinate [FeNO](6) complexes. On the basis of resonance Raman and FTIR
      data, a direct correlation between the nu(Fe)(-)(NO) and nu(N)(-)(O) frequencies
      of [Fe(OEP)NO](ClO(4)) and [Fe(OEP)NO](ClO(4)).CHCl(3) (two crystal forms of the
      same complex) has been established. Density functional theory calculations show
      that the relationship between Fe-NO and N-O bond strengths is responsive to FeNO
      electron density in three molecular orbitals. The highest energy orbital of the
      three is sigma-antibonding with respect to the entire FeNO unit. The other two
      comprise a lower-energy, degenerate, or nearly degenerate pair that is pi-bonding
      with respect to Fe-NO and pi-antibonding with respect to N-O. The relative
      sensitivities of the electron density distributions in these orbitals are shown
      to be consistent with all published indicators of Fe-N-O bond strengths and
      angles, including the examples reported here.

PMID- 15506780
TI  - Hydrogen-bonded encapsulation complexes in protic solvents.
AB  - We describe here the behavior of the hydrogen-bonded capsule 1.1 and its
      complexes in protic solvents. The kinetics and thermodynamics of the
      encapsulation process were determined through conventional (1)H NMR methods. The
      enthalpies and entropies of encapsulation are both positive, indicating a process
      that liberates solvent molecules. The rates of dissociation-association of the
      capsule were comparable to the rates for the in-out exchange of large guests,
      which suggests that guest exchange occurs by complete dissociation of the capsule
      in protic solvents. The stability of the hydrogen-bonded capsule 1.1 toward
      protic solvents depends strongly on the guests, with the best guest being
      dimethylstilbene 8. The results establish guidelines for the properties of
      capsules that could be accessed in water.

PMID- 15506782
TI  - Organotellurium(VI) azides and halides.
AB  - The reaction of azide with organotellurium(VI) halides Ph(5)TeBr and cis
      (biphen)(2)TeF(2) (biphen = 2,2'-biphenyldiyl) resulted in the formation and
      isolation of Ph(5)TeN(3) (1) and cis-(biphen)(2)Te(N(3))(2) (2), which are the
      first tellurium(VI)-azide species. In addition to spectroscopic data, both
      crystal structures have been determined. Furthermore, the stability of possible
      Te(VI) species with higher azide contents Ph(x)()Te(N(3))(6)(-)(x)() and
      Me(x)()Te(N(3))(6)(-)(x)() as well as the syntheses and properties of their
      Ph/Me(x)()TeF(y)() precursors was investigated, including the crystal structure
      determination of trans-Ph(2)TeF(4) (3). Ab initio and density functional studies
      of all molecules regarding the structures and electronic populations were
      performed.

PMID- 15506781
TI  - Roles of anionic and cationic template components in biomineralization of CdS
      nanorods using self-assembled DNA-membrane complexes.
AB  - Complexes of anionic DNA and cationic liposomes self-assemble into a
      multilamellar structure where two-dimensional lipid sheets confine a periodic one
      dimensional lattice of parallel DNA chains, between which Cd(2+) ions can
      condense, and be subsequently reacted with H(2)S to form CdS nanorods. In this
      work, we identify the synergistic roles of the anionic and cationic components
      within the DNA-membrane template; DNA is highly anionic and condenses the Cd(2+)
      ions, while the cationic membrane modulates the concentration of condensed Cd(2+)
      ions to control the final CdS nanorod dimensions. Due to the strong electrostatic
      interactions between the DNA sugar-phosphate backbone and the Cd(2+) ions,
      crystallographic control of CdS nanostructures is possible using these simple DNA
      membrane templates, which we demonstrate using nanobeam electron diffraction
      experiments on individual templated CdS nanorods.

PMID- 15506783
TI  - A combined experimental and computational study of
      dihydrido(phosphinooxazoline)iridium complexes.
AB  - The reaction of a [(PHOX)Ir(COD)](+) complex (COD = 1,5-cyclooctadiene) with
      dihydrogen was studied by NMR spectroscopy (PHOX = chiral phosphinooxazoline
      ligand). A single [(PHOX)Ir(H)(2)(COD)](+) isomer was formed as the primary
      product at -40 degrees C in THF. Subsequent reaction with H(2) at -40 to 0
      degrees C led to a mixture of two diastereomeric [(PHOX)Ir(H)(2)(solvent)(2)](+)
      complexes with concomitant loss of cyclooctane. The stereochemistry of the three
      hydride complexes could be assigned from the NMR data. The structures and
      energies of the observed hydride complexes and the possible stereoisomers were
      calculated using density functional theory. The substantial energy differences
      (up to 39 kcal/mol) between the various stereoisomers demonstrate the strong
      influence of the chiral ligand. The observed stereoselective formation of
      dihydride complexes can be explained by steric effects of the PHOX ligand
      combined with a strong electronic influence of the coordinating N and P atoms,
      favoring addition of a hydride trans to the Ir-N bond.

PMID- 15506784
TI  - Oscillation of conductance in molecular junctions of carbon ladder compounds.
AB  - The electrical conductances of dithiolates of polyacene (PA(n)DTs) and
      polyphenanthrene (PPh(n)DTs), which are typical carbon ladder compounds, are
      calculated by means of the Landauer formulation combined with density functional
      theory, where n is the number of benzene rings involved. Surface Green function
      used in the Landauer formulation is calculated with the Slater-Koster parameters.
      Attention is turned to the wire-length dependence of the conductances of PA(n)DTs
      and PPh(n)DTs. The damping of conductance of PA(n)DTs is much smaller than that
      of PPh(n)DTs because of the small HOMO-LUMO gaps of PA(n)DTs. PA(n)DTs are thus
      good molecular wires for nanosized electronic devices. Conductance oscillation is
      found for both molecular wires when n is less than 7. The electrical conductance
      is enhanced in PA(n)DTs with even-numbered benzene rings, whereas it is enhanced
      in PPh(n)DTs with odd-numbered benzene rings. The observed conductance
      oscillation of PA(n)DTs and PPh(n)DTs is due to the oscillation of orbital energy
      and electron population. Other pi-conjugated oligomers (polyacetylene-DT,
      oligo(thiophene)-DT, oligo(meso-meso-linked zinc(II) porphyrin-butadiynylene)-DT,
      oligo(p-phenylethynylene)-DT, and oligo(p-phenylene)-DT) are also studied. In
      contrast to PA(n)DTs and PPh(n)DTs, the five molecular wires show ordinary
      exponential decays of conductance.

PMID- 15506785
TI  - Calculation of trans-hydrogen-bond 13C-15N three-bond and other scalar J
      couplings in cooperative peptide models. A density functional theory study.
AB  - We report B3LYP DFT calculations on peptide models that consider the effects of
      cooperative interactions with proximate H-bonds and local geometry at the H
      bonding site upon trans-H-bond (13)C-(15)N three-bond scalar J-couplings. The
      calculations predict that cooperative interactions with other H-bonds within a H
      bonding chain can significantly increase the magnitude of these couplings. Such
      increases are due to a combination of the presence of the neighboring H-bonds and
      the slight increase in C=O distances expected for peptide H-bonds near the
      centers of H-bonding chains. The energies of H-bonds inferred from H-bonding
      distances, alone, could be significantly in error if the effects of neighboring H
      bonds are ignored.

PMID- 15506786
TI  - Comparison of fully optimized alpha- and 3(10)-helices with extended beta
      strands. An ONIOM density functional theory study.
AB  - We compare the structures and energies of beta-strands, alpha-helices, and 3(10)
      helices for capped polyalanines, acetyl(ala)(N)()NH(2), for values of N from 2 to
      18, using completely optimized mixed DFT/AM1 calculations. Non-pairwise additive
      cooperativity is manifest from the variation of the relative energies, helical
      strain, dipole moments, and H-bond lengths of both types of helices, but
      especially for the alpha-helices. While the gas-phase 3(10)-helices are more
      stable for small polyalanines, largely due to the additional H-bond, the alpha
      helices become relatively more stable as the polyalanines increase in size.

PMID- 15506787
TI  - Perturbations by phenyl on the 1,5-hydrogen shift in 1,3(Z)-pentadiene. Another
      chameleonic transition region?
AB  - The acyclic 1,5-dienyl hydrogen shift is accelerated by radical-stabilizing
      phenyl substituents without regard to the type of position occupied in the 1,3(Z)
      pentadiene system. 1-Phenyl-5-p-tolyl-1,3(Z)-pentadiene has a corrected energy of
      activation 5.8 kcal mol(-)(1) lower than that of the parent, while the 2- and 3
      phenyl analogues, examined in cyclic systems specifically designed to obviate the
      otherwise general need for a thermochemical correction to the immediately
      precursory s-cis conformation, reveal stabilizing effects of 3.6 and 3.4 kcal
      mol(-)(1), respectively. These relatively small effects are consistent with a
      chameleonic conceptual scheme for the transition region.

PMID- 15506788
TI  - Effects of benzyl ether type dendrons as hole-harvesting antennas, and shielding
      for the neutralization of stilbene core radical cations with chloride ion during
      two-photon ionization of stilbene dendrimers having stilbene core and benzyl
      ether type dendrons.
AB  - The two-photon ionization (TPI) process (308 and 266 nm) of stilbene dendrimers
      having a stilbene core and benzyl ether type dendrons has been investigated in an
      acetonitrile and 1,2-dichloroethane mixture (3:1) in order to elucidate the
      dendrimer effects. The quantum yield of the formation of stilbene core radical
      cation during the 308-nm TPI was independent of the dendron generation of the
      dendrimers, whereas a generation dependence of the quantum yield of the radical
      cation was observed during the 266-nm TPI, where both the stilbene core and
      benzyl ether type dendron were ionized, suggesting that the subsequent hole
      transfer occurs from the dendron to the stilbene core, and that the dendron acts
      as a hole-harvesting antenna. The neutralization rate of the stilbene core
      radical cation with the chloride ion, generated from the dissociative electron
      capture by 1,2-dichloroethane, decreased with the increase in the dendrimer
      generation, suggesting that the dendron is an effective shield of the stilbene
      core radical cation against the chloride ion.

PMID- 15506789
TI  - Factors controlling the complex architecture of native and modified cyclodextrins
      with dipeptide (Z-Glu-Tyr) studied by microcalorimetry and NMR spectroscopy:
      critical effects of peripheral bis-trimethylamination and cavity size.
AB  - Complex stability constant (K), standard free energy (DeltaG degrees ), reaction
      enthalpy (DeltaH degrees ), and entropy change (TDeltaS degrees ) for 1:1
      inclusion complexation of the diastereomeric dipeptides Z-d/l-Glu-l-Tyr (Z =
      benzyloxycarbonyl) and its component amino acids (Z-d/l-Glu and N-Ac-Tyr) with
      native alpha-, beta-, and gamma-cyclodextrins (CDs) and A,X-modified bis(6
      trimethylammonio-6-deoxy)-beta-CDs (AX-TMA(2)-beta-CDs) were determined in buffer
      solution (pH 6.9) at T = 298.15 K by isothermal titration microcalorimetry.
      Concurrent NMR spectral examinations revealed that the penetration mode and the
      resulting complex architecture are dramatically altered by the peripheral
      modification and also by the CD's cavity size. Upon complexation of the ditopic Z
      Glu-Tyr guest, native alpha- and beta-CDs preferentially bind the Z's phenyl
      group, whereas AX-TMA(2)-beta-CDs predominantly include the Tyr's phenol moiety.
      In contrast, native gamma-CD includes both of the aromatic moieties
      simultaneously in the same cavity. Furthermore, for isomeric AB-, AC, and AD
      TMA(2)-beta-CDs, an inversion of enantioselectivity and a switching of the
      penetration mode were observed, critically depending on the position of TMA
      substituents.

PMID- 15506790
TI  - Adsorption-induced asymmetric assembly from an achiral adsorbate.
AB  - Symmetry breaking in the self-assembled monolayer (SAM) structure of 1
      octadecanol on highly ordered pyrolytic graphite (HOPG) is observed. Due to the
      slight mismatch of the octadecanol molecule with the graphite lattice, the alkane
      chain undergoes distortion upon adsorption on the surface. The asymmetric
      distortion of the octadecanol SAM unit cell pair is observed by scanning
      tunneling microscopy at the liquid/solid interface. Asymmetric distortion is due
      to the requirement for planarity of the hydrogen bond connecting the two
      octadecanol molecules in the chevron-shaped unit cell. This very simple structure
      provides the first example of an adsorption-induced distortion to form a
      supramolecular asymmetric structure, which is formed by achiral molecules
      adsorbed on an achiral surface. What makes this system interesting and different
      from other examples of adsorption-induced chirality is that the adsorbate itself
      undergoes asymmetric distortion due to the existence of the substrate and the
      adsorbate conformation is different from the molecule in solution.

PMID- 15506791
TI  - Carbon monoxide as an intrinsic ligand to iron in the active site of the iron
      sulfur-cluster-free hydrogenase H2-forming methylenetetrahydromethanopterin
      dehydrogenase as revealed by infrared spectroscopy.
AB  - The iron-sulfur-cluster-free hydrogenase Hmd (H(2)-forming
      methylenetetrahydromethanopterin dehydrogenase) from methanogenic archaea has
      recently been found to contain one iron associated tightly with an extractable
      cofactor of yet unknown structure. We report here that Hmd contains intrinsic CO
      bound to the Fe. Chemical analysis of Hmd revealed the presence of 2.4 +/- 0.2
      mol of CO/mol of iron. Fourier transform infrared spectra of the native enzyme
      showed two bands of almost equal intensity at 2011 and 1944 cm(-)(1), interpreted
      as the stretching frequencies of two CO molecules bound to the same iron in an
      angle of 90 degrees . We also report on the effect of extrinsic (12)CO, (13)CO,
      (12)CN(-), and (13)CN(-) on the IR spectrum of Hmd.

PMID- 15506792
TI  - Effect of weak interactions on the H...H distance in stretched dihydrogen
      complexes.
AB  - Computational and experimental results presented in this paper demonstrate that
      the H-H distance in stretched dihydrogen complexes can be hypersensitive to a
      variety of weak intra- and intermolecular interactions, including those with
      bulky ligands and solvent molecules, hydrogen-bonding interactions, or ion
      pairing. Particularly, the complex IrH(H...H)Cl(2)(P(i)Pr(3))(2) which contains a
      stretched dihydrogen ligand in the crystalline form, as shown by neutron
      diffraction, is a trihydride in solution. The difference is due to the
      intermolecular Ir-Cl...H-Ir hydrogen bonding in the solid.

PMID- 15506793
TI  - Epitope mapping and competitive binding of HSA drug site II ligands by NMR
      diffusion measurements.
AB  - It is important to characterize drug-albumin binding during drug discovery and
      lead optimization as strong binding may reduce bioavailability and/or increase
      the drug's in vivo half-life. Despite knowing about the location of human serum
      albumin (HSA) drug binding sites and the residues important for binding, less is
      understood about the binding dynamics between exogenous drugs and endogenous
      fatty acids. In contrast to highly specific antibody-antigen interactions, the
      conformational flexibility of albumin allows the protein to adopt multiple
      conformations of approximately equal energy in order to accommodate a variety of
      ligands. Nuclear magnetic resonance (NMR) diffusion measurements are a simple way
      to quantitatively describe ligand-protein interactions without prior knowledge of
      the number of binding sites or the binding stoichiometry. This method can also
      provide information about ligand orientation at the binding site due to buildup
      of exchange-transferred NOE (trNOE) on the diffusion time scale of the
      experiment. The results of NMR diffusion and NOE experiments reveal multiple
      binding interactions of HSA with dansylglycine, a drug site II probe, and
      caprylate, a medium-chain fatty acid that also has primary affinity for HSA's
      drug site II. Interligand NOE (ilNOE) detected in the diffusion analysis of a
      protein solution containing both ligands provides insight into the conformations
      adopted by these ligands while bound in common HSA binding pockets. The results
      demonstrate the ability of NMR diffusion experiments to identify ternary complex
      formation and show the potential of this method for characterizing other
      biologically important ternary structures, such as enzyme-cofactor-inhibitor
      complexes.

PMID- 15506794
TI  - Importance of structural tightening, as opposed to partially bound States, in the
      determination of chemical shift changes at noncovalently bonded interfaces.
AB  - Two models (A and B) have been proposed to account for decreased downfield
      chemical shifts of a proton bound by noncovalent interactions at a
      ligand/antibiotic interface as the number of ligand/antibiotic interactions is
      decreased. In model A, the proton involved in the noncovalent bond suffers a
      smaller downfield shift because the bond is, with a relatively large probability,
      broken, and not because it is longer. In model B, the proton involved in the
      noncovalent bond suffers a smaller downfield shift because the bond is longer,
      and not because it is, with a relatively large probability, broken. We show that
      model A cannot account for the chemical shift changes. Model B accounts for the
      process of positively cooperative binding, in which noncovalent bonds are reduced
      in length and thereby increase the stability of the organized state.

PMID- 15506795
TI  - Direct sticking and differential adsorption heats as probes of structural
      transitions: O2 on the stepped Ni[211] surface.
AB  - Coverage-dependent heats of adsorption and sticking probabilities for oxygen on
      Ni[211] have been measured at 300 K using single-crystal adsorption calorimetry.
      The data are consistent with a switch from dissociative chemisorption at low
      coverage to oxide formation above 2 ML adatom coverage. The initial heat of
      adsorption is 620 kJ mol(-)(1), considerably higher than for any low Miller index
      nickel surface; this is attributed to the presence of low coordination step atoms
      that are preferably occupied up to 1 ML. As the coverage increases, the heat is
      found to drop very rapidly, indicating the presence of strong lateral adatom
      repulsions, which ultimately drive a transition from the chemisorption regime to
      oxide film formation at higher coverage. The shape of the coverage-dependent
      sticking probability is consistent with a direct adsorption mechanism at low
      coverage. At higher coverage, the transition between the chemisorption and
      oxidation regimes is relatively complex compared with low Miller index nickel
      surfaces. This is discussed in terms of the influence of the step sites on the
      [211] surface.

PMID- 15506796
TI  - Computer simulation of solid and liquid benzene with an atomistic interaction
      potential derived from ab initio calculations.
AB  - Molecular dynamics atomistic simulations of solid and liquid benzene have been
      performed, employing a model intermolecular potential derived from quantum
      mechanical calculations. The ab initio database includes approximately 200
      geometries of the benzene dimer with interaction energies computed at the MP2
      level of theory. The accuracy of the modeled force field results is satisfactory.
      The thermodynamic and structural properties, calculated in the condensed phases,
      are compared with experimental data and previous simulation results. Single
      particle and collective dynamical properties are also investigated through the
      calculation of translational and rotational diffusion coefficients,
      reorientational dynamics, and viscosities. The agreement of these data with
      experimental measurements confirms the reliability of the proposed force field.

PMID- 15506797
TI  - Length-dependent transport in molecular junctions based on SAMs of alkanethiols
      and alkanedithiols: effect of metal work function and applied bias on tunneling
      efficiency and contact resistance.
AB  - Nanoscopic tunnel junctions were formed by contacting Au-, Pt-, or Ag-coated
      atomic force microscopy (AFM) tips to self-assembled monolayers (SAMs) of
      alkanethiol or alkanedithiol molecules on polycrystalline Au, Pt, or Ag
      substrates. Current-voltage traces exhibited sigmoidal behavior and an
      exponential attenuation with molecular length, characteristic of nonresonant
      tunneling. The length-dependent decay parameter, beta, was found to be
      approximately 1.1 per carbon atom (C(-1)) or 0.88 A(-)(1) and was independent of
      applied bias (over a voltage range of +/-1.5 V) and electrode work function. In
      contrast, the contact resistance, R(0), extrapolated from resistance versus
      molecular length plots showed a notable decrease with both applied bias and
      increasing electrode work function. The doubly bound alkanedithiol junctions were
      observed to have a contact resistance approximately 1 to 2 orders of magnitude
      lower than the singly bound alkanethiol junctions. However, both alkanethiol and
      dithiol junctions exhibited the same length dependence (beta value). The
      resistance versus length data were also used to calculate transmission values for
      each type of contact (e.g., Au-S-C, Au/CH(3), etc.) and the transmission per C-C
      bond (T(C)(-)()(C)).

PMID- 15506798
TI  - Light-mediated C-C sigma-bond driven crystallization of a phenalenyl radical
      dimer.
AB  - Polymorphism-the phenomenon that a given compound forms more than one crystalline
      arrangement of the molecules in the solid state- plays a crucial role in
      understanding organic conductors, superconductors, and magnets. We have found
      that solutions of a new phenalenyl radical can give rise to two (nonpolymorphic)
      crystalline forms depending on whether the crystallization is allowed to proceed
      in the presence or absence of light. In both cases the crystals take the form of
      black shining blades and are indistinguishable by optical microscopy. We have
      fully characterized these crystalline forms, and we show that they differ by the
      presence or absence of a C-C sigma-bond between the unpaired electrons of the
      parent radical. These molecular forms crystallize from the same solvent to give
      rise to a sigma-dimerized insulator and a monomeric radical semiconductor as
      dictated by the presence or absence of light.

PMID- 15506799
TI  - Cluster analysis applied to the exploratory analysis of commercial spanish olive
      oils by means of excitation-emission fluorescence spectroscopy.
AB  - Olive oil fluorescence is related to oil composition. Here it is shown that the
      natural clustering of different types of commercial Spanish olive oils depends on
      their fluorescence excitation-emission matrices (EEMs). Fifty-six commercial
      samples of olive oil (29 virgin olive oils, 20 pure olive oils, and 7 olive
      pomace oils) were used. The clustering method was hierarchical agglomerative
      clustering using the Euclidean distance as a similarity measure and the average
      linkage. Two spectral ranges were considered (which either contained the
      fluorescence peak of the chlorophylls or did not), and various methods for
      preprocessing the fluorescence spectra were compared. The oils were clearly
      distinguished using the unfolded EEMs measured between lambda(ex) = 300-400 nm
      and lambda(em) = 400-600 nm. The optimal preprocessing was normalization of the
      unfolded spectra followed by column autoscaling. Also shown are the advantages of
      using second-order data (EEMs) instead of first-order data (a single fluorescence
      spectrum) for each sample.

PMID- 15506800
TI  - Development of an ELISA for the detection of the residues of the fungicide
      iprovalicarb.
AB  - A competitive indirect enzyme-linked immunosorbent assay was developed for the
      fungicide iprovalicarb, using a polyclonal antibody produced against a hapten
      conjugated through the carboxyl group on the benzene ring to keyhole limpet
      hemocyanin. Under an optimized condition using a heterologous format, an IC(50)
      of 3.51 ng/mL and the lowest detection limit of 0.065 ng/mL were obtained. When
      the isopropoxy group was removed from the iprovalicarb structure for the
      synthesis of a hapten, the resulting hapten was not successful as an immunogen,
      indicating that the isopropyl moiety was an important epitope, as evidenced by
      the cross-reactivities of some structurally related compounds. When applied to
      the real crop and water samples, the recoveries were in the range of 80.52
      144.70% (n = 4) and 72.11-100.43% (n = 4), respectively. Accordingly, this ELISA
      can be used as a useful method for monitoring iprovalicarb residues in crop and
      water samples.

PMID- 15506801
TI  - Sensitive determination of phenolic acids in extra-virgin olive oil by capillary
      zone electrophoresis.
AB  - A sensitive, rapid, efficient, and reliable method for the separation and
      determination of phenolic acids by capillary zone electrophoresis has been
      carried out. A detailed method optimization was carried out to separate 14
      different compounds by studying parameters such as pH, type and concentration of
      buffer, applied voltage, and injection time. The separation was performed within
      16 min, using a 25 mM sodium borate buffer (pH 9.6) at 25 kV with 8 s of
      hydrodynamic injection. With this method and using a liquid-liquid extraction
      system, with recovery values around 95%, it has been possible to detect small
      quantities of phenolic acids in olive oil samples. This is apparently the first
      paper showing the quantification of this specific family of phenolic compounds in
      virgin olive oil samples.

PMID- 15506802
TI  - Identification of flavonoids in Hakmeitau beans (Vigna sinensis) by high
      performance liquid chromatography-electrospray mass spectrometry (LC-ESI/MS).
AB  - Liquid chromatography coupled with electrospray mass spectrometry (LC-ESI/MS)
      with positive and negative ion detection was used for the identification of
      flavonoids in Hakmeitau beans, a black seed cultivar of cowpea (Vigna sinensis).
      Gradient elution with water and acetonitrile, both containing 2% formic acid, was
      employed in chromatographic separation. The peaks were identified by comparison
      of the retention times and the UV-vis spectroscopic and mass spectrometric data
      with authentic standards and/or literature data. The identified flavonoids
      included six anthocyanins (cyanidin 3-O-galactoside, cyanidin 3-O-glucoside,
      delphinidin 3-O-glucoside, malvidin 3-O-glucoside, peonidin 3-O-glucoside, and
      petunidin 3-O-glucoside) and four flavonol/flavonol glycosides (kaempferol 3-O
      glucoside, quercetin, quercetin 3-O-glucoside, and quercetin 3-O-6' '
      acetylglucoside). The tentatively identified flavonoids included two anthocyanins
      (malvidin 3-O-acetylglucoside and peonidin 3-O-malonylglucoside) and three
      flavonol glycosides (myricetin-3-O-glucoside, quercetin 7-O-glucoside, and
      quercetin-3-O-diglucoside). These flavonoids are present in seed coats, and the
      contents of anthocyanins and flavonol glycosides were 20.7 and 2.0 mg/g,
      respectively.

PMID- 15506803
TI  - Determination of acequinocyl and hydroxyacequinocyl on fruits and vegetables by
      HPLC-DAD.
AB  - A method for determining residues of the new reduced-risk pesticide acequinocyl
      and its deacetylated derivative hydroxyacequinocyl on fruits and vegetables
      (grapes, lemons, pears, and tomatoes) by HPLC is described. The pesticides were
      extracted from the fruits and vegetables with hexane and ethyl acetate solution
      (1:1, v/v), determined by HPLC-DAD at 250 nm and confirmed by LC/MS. No cleanup
      was necessary. This method is characterized by recoveries (0.01-4 mg/kg) > 77%,
      while the coefficient of variation was determined to be less than 11%. The limit
      of quantitation for both acequinocyl and hydroxyacequinocyl was 0.01 mg/kg for
      all matrixes.

PMID- 15506804
TI  - Effects of glucosinolates and their enzymatic hydrolysis products via myrosinase
      on the root-knot nematode Meloidogyne incognita (Kofoid et White) Chitw.
AB  - The root-knot nematode Meloidogyne incognita (Kofoid et White) Chitw. is
      responsible for large yield losses in several horticultural crops. Fumigation
      with chemicals has been efficient in fighting this soil pest, but it clearly
      shows a negative environmental impact. Thus, it is necessary to find an
      environmentally friendly alternative to control this nematode and meet the
      requirements imposed by world regulation to ban some chemical fumigants in the
      world after 2005. The glucosinolate-myrosinase system, typical of the
      Brassicaceae family, appears to be an important natural alternative for the
      control of several soilborne pests and pathogens. The aim of this study was to
      evaluate, in vitro, the biocidal activity of 11 glucosinolates and their
      degradation products on second-stage juveniles of the root-knot nematode M.
      incognita expressed by the nematicidal (LD(50)) and immobilization effects, after
      24 and 48 h. None of the intact glucosinolates had any biological effect. After
      myrosinase addition, their hydrolysis products (essentially isothiocyanates)
      resulted in highly different biocidal activities. Among the hydrolysis products
      of the tested glucosinolates, 2-phenylethyl, benzyl, 4-methylthiobutyl, and prop
      2-enyl isothiocyanate showed the stronger activity, with an LD(50) at
      concentrations of 11, 15, 21, and 34 microM, respectively. On the basis of the in
      vitro test results, new genotypes of Brassicaceae had been selected for high
      content in the roots of the glucosinolates generating the more active
      isothiocyanates and their agronomic performances verified in view of a full-field
      application as catch crop plants. With this aim, the qualitative and quantitative
      glucosinolate contents in the roots of these potentially nematicidal plants are
      also reported and discussed.

PMID- 15506805
TI  - Chemical composition and larvicidal activity of the essential oils from
      Eupatorium betonicaeforme (D.C.) Baker (Asteraceae).
AB  - The volatile composition of the essential oils from leaves and roots of
      Eupatorium betonicaeforme (D.C.) Baker was analyzed by GC-MS. A total of 12
      compounds were identified. beta-Caryophyllene (12.4-41.7%), alpha-humulene (11.7
      14.6%), gamma-muurolene (10.4-19.0%), bicyclogermacrene (15.0-17.5%), 2,2
      dimethyl-6-vinylchroman-4-one (10.3-25.5%), and 2-senecioyl-4-vinylphenol (8.5
      41.0%) were the most prominent constituents. The former two compounds were
      isolated and characterized by spectroscopic data. The essential oils and the
      isolated compounds were tested against Aedes aegypti larvae survival. The results
      obtained show that the essential oil from roots and 2,2-dimethyl-6-vinylchroman-4
      one (10.3-25.5%) could be considered as natural larvicidal agents.

PMID- 15506806
TI  - Antioxidant oligomeric proanthocyanidins from sea buckthorn (Hippophae
      rhamnoides) Pomace.
AB  - After flavonol glycosides, monomeric flavan-3-ols, and dimeric and trimeric
      proanthocyanidins were fractionated from an extract of sea buckthorn (Hippophae
      rhamnoides) pomace by Sephadex LH-20 gel chromatography, oligomeric
      proanthocyanidins were eluted. The oligomeric fraction accounted for 84% of the
      total proanthocyanidins and 75% of the total antioxidant activity of the sea
      buckthorn pomace extract. To elucidate the structure of the oligomeric fraction,
      it was depolymerized by acid catalysis in the presence of phloroglucinol. The
      structure of the resulting flavan-3-ol monomers and flavan-3-ol-phloroglucinol
      adducts was determined by electrospray ionization mass spectrometry (ESI-MS) and
      (1)H and (13)C nuclear magnetic resonance (NMR) spectroscopy. Quantitative high
      performance liquid chromatography investigations demonstrated (+)-gallocatechin
      as the predominating subunit in the oligomeric fraction. This observation was
      confirmed by ESI-MS, matrix-assisted laser desorption/ionization mass
      spectrometry, and (13)C NMR spectroscopy. The results showed that the majority of
      the flavan-3-ol subunits possessed a 2,3-trans configuration. The oligomers
      consisted mainly of prodelphinidin subunits whereas procyanidins were present in
      smaller amounts, indicating a very uncommon composition of the sea buckthorn
      proanthocyanidins. The mean degree of polymerization of the oligomeric
      proanthocyanidins was between 6 and 9.

PMID- 15506807
TI  - Synthesis and antifeeding activities of Tonghaosu analogues.
AB  - Tonghaosu (1), a lead for a botanical antifeedant, and its 22 analogues were
      synthesized according to a previously reported concise and straightforward
      procedure. The structures of all new compounds were confirmed by NMR, IR, MS, and
      HREIMS or elemental analysis. Their insect antifeedant activities against the
      large white butterfly (Pieris brassicae L.) were examined, and six analogues (Z-
      and E-6h and Z-isomers of 6i-l), which contain 1,3-diyn or 3,4
      methylenedioxyphenyl acetylene group, showed considerable antifeedant activity.
      Interestingly, Z-isomers of 6i-k are much more active than their corresponding E
      isomers.

PMID- 15506808
TI  - Biochemical and molecular analysis of carotenoid biosynthesis in flavedo of
      orange (Citrus sinensis L.) during fruit development and maturation.
AB  - Changes in carotenoid content and composition and expression of carotenoid
      biosynthetic genes were analyzed in the flavedo of sweet orange (Citrus sinensis
      L. Osbeck, cv. Navelate) fruit during development and maturation. Lutein and all
      E-violaxanthin were the major carotenoids in chloroplast-containing tissues.
      During fruit coloration, phytoene, beta-cryptoxanthin, zeaxanthin, and mainly
      (9Z)-violaxanthin progressively accumulated, and a large proportion of
      apocarotenoids was also found in the flavedo of full-colored fruits. We have
      cloned partial and full-length cDNAs corresponding to genes involved in early
      condensation and desaturase reactions [phytoene synthase (PSY), phytoene
      desaturase (PDS), and zeta-carotene desaturase (ZDS)], coupled redox reaction
      (plastid terminal oxidase), cyclizations [beta-lycopene cyclase (beta-LCY) and
      epsilon-lycopene cyclase (epsilon-LCY)], hydroxylation [beta-carotene hydroxylase
      (beta-CHX)], and epoxidation [zeaxanthin epoxidase (ZEP)] and analyzed their mRNA
      accumulation in the flavedo of fruits during development and ripening as compared
      with those of leaves. Collectively, the results indicated that PDS gene
      expression correlated with carotenoid content in developing fruit and that up
      regulation of PSY and ZDS genes at the onset of fruit coloration would enhance
      the production of linear carotenes and the flux into the pathway. The shift from
      the beta,epsilon-branch to the beta,beta-branch of the pathway that originates
      the changes in carotenoid composition during fruit coloration may be explained by
      a down-regulation of epsilon-LCY and by the increase of the beta-CHX transcript.

PMID- 15506809
TI  - Ratio of maltose to maltulose and furosine as quality parameters for infant
      formula.
AB  - Nonenzymic browning reactions in commercial infant formulas were evaluated
      through their furosine content as well as the isomeric disaccharides formed
      during processing. Lactulose was observed only in samples containing appreciable
      amounts of lactose, whereas maltulose was present in all samples due to the
      isomerization of maltose. Because formation of maltulose depends on the initial
      amount of maltose present, the ratio maltose/maltulose was used for comparative
      purposes. The ratio maltose/maltulose varied within a wide range, 27-167;
      therefore, low values in maltose/maltulose ratio may indicate severe processing
      conditions during manufacture, whereas high values may indicate mild processing
      conditions. Variable amounts of furosine content in samples with similar
      maltose/maltulose ratios may be attributed to different conditions used during
      storage. Levels of furosine higher than those reported for milk powder were
      detected in most studied samples. Determination of both furosine and
      maltose/maltulose ratio would yield information retrospectively about the heat
      treatment applied during processing and the storage conditions of commercial
      infant formula.

PMID- 15506810
TI  - Synthesis and insecticidal evaluation of novel N-oxalyl derivatives of
      tebufenozide.
AB  - A series of novel N '-tert-butyl-N '-3,5-dimethylbenzoyl-N-aryloxyoxalyl-N-4
      ethylbenzoyl hydrazines containing a carboxylic acid or ester substituent on the
      aryl were synthesized, and their larvicidal activities were evaluated. The
      results of bioassays indicated that some of these title compounds exhibit higher
      larvicidal activities than RH5849 (N-tert-butyl-N,N '-dibenzoylhydrazine), but
      they are not good compared to the parent compound (tebufenozide). The carboxylic
      acid substituent on the aryl was essential for high larvicidal activity. Compared
      to the parent compound, these derivatives displayed different physical
      properties, for example, better solubility in organic solvents. Toxicity assays
      indicated that these derivatives could induce a premature, abnormal, and lethal
      larval molt.

PMID- 15506811
TI  - Volatilization of alachlor from polymeric formulations.
AB  - Pesticides may be dispersed throughout the environment by several means,
      including groundwater contamination, surface water contamination, and
      volatilization with subsequent atmospheric transport and deposition. In earlier
      research primarily directed at reducing the potential for groundwater
      contamination, a number of herbicides were microencapsulated within several
      different polymers. These polymeric formulations were evaluated for efficacy in
      the greenhouse. In the studies described in this paper, three polymeric alachlor
      formulations that were the most effective in the greenhouse were evaluated in
      laboratory volatility studies using pure alachlor and a commercial formulation
      (Lasso 4EC) for comparison purposes. In a given experiment, technical alachlor,
      Lasso 4EC, and two polymeric formulations were applied to soil and evaluated in a
      contained system under 53% humidity with a fixed flow rate. Evolved alachlor was
      collected in ethylene glycol, recovered with C18 solid phase extraction
      cartridges, and analyzed by reverse-phase high-performance thin-layer
      chromatography with densitometry. Duration of the studies ranged from 32 to 39
      days. In studies in which all formulations were uniformly incorporated in the
      soil, total alachlor volatilization from the polymeric microcapsules was
      consistently lower than that from the alachlor and Lasso 4EC formulations. In
      studies in which the polymeric formulations were sprinkled on the surface of the
      soil, microcapsules prepared with the polymer cellulose acetate butyrate released
      the smallest quantity of volatilized alachlor.

PMID- 15506812
TI  - Influence of humic acid on adsorption and desorption of atrazine,
      hydroxyatrazine, deethylatrazine, and deisopropylatrazine onto a clay-rich soil
      sample.
AB  - Adsorption and desorption properties of atrazine and some of its metabolites,
      hydroxyatrazine (AT-OH), deethylatrazine (DEA), and deisopropylatrazine (DIA),
      were studied with a clay-rich soil sample (clay content of 53%). A part of this
      soil was treated with humic acid (Soil-HA) to assess the influence of this
      important component of natural organic matter on adsorption and desorption
      processes. This study was performed using the batch approach with 1.0 g of soil,
      or Soil-HA, in 5.0 mL of 0.010 mol L(-)(1) CaCl(2) solution containing the
      herbicide and the metabolites in a concentration range between 0.010 and 5.0 mg
      L(-)(1). After 24 h of contact time, the suspensions were centrifuged and the
      four compounds were quantified in the supernatant phases by high-performance
      liquid chromatography. The adsorption and desorption data of both Soil and Soil
      HA were properly fitted by the linearized Freundlich equation. For the untreated
      soil, the adsorption affinity order evaluated as a function of the K(f) values
      was AT-OH > AT > DIA > DEA, while desorption followed the order DEA > DIA
      approximately AT > AT-OH. The presence of humic acid increased significantly the
      adsorption of all compounds, following the same affinity order observed for the
      untreated soil. Increase in adsorption was especially high for AT-OH and AT. On
      the other hand, the dealkylated metabolites, DEA and DIA, were more easily
      desorbed from the Soil-HA sample, suggesting that natural organic matter
      facilitates the leaching of these compounds. Desorption order in the presence of
      humic acid was DEA > DIA > AT > AT-OH.

PMID- 15506813
TI  - Influence of the brewing process on furfuryl ethyl ether formation during beer
      aging.
AB  - In beer, the development of a solvent-like stale flavor is associated with the
      formation of furfuryl ethyl ether. The synthesis rate of this important flavor
      compound is proportional to the concentration of furfuryl alcohol in beer. This
      study shows that furfuryl alcohol in beer is mainly formed by Maillard reactions
      initiated during wort boiling and malt production. A mechanism for its formation
      from alpha-(1,4)-oligoglucans and amino acids in wort and beer is proposed.
      During wort boiling, a quadratic relationship was found between the wort extract
      concentration, on the one hand, and the increase of furfuryl alcohol and
      furfural, on the other. The reduction of furfural by yeast during fermentation
      further increases the furfuryl alcohol content. In pale beers, the furfuryl
      alcohol concentration is essentially determined by the thermal load on wort
      during brewing operations. In dark beers, a considerable fraction of furfuryl
      alcohol may, however, come from the dark malts used. These results lead to
      important practical conclusions concerning the control over furfuryl ethyl ether
      in beer.

PMID- 15506814
TI  - 3-Hydroxy-4,5-dimethyl-2(5H)-furanone levels in fortified Madeira wines:
      relationship to sugar content.
AB  - The maturation of Madeira wines usually involves exposure to relatively high
      temperatures and humidity levels >70%, which affect the aroma and flavor
      composition and lead to the formation of the typical and characteristic bouquet
      of these wines. To estimate the levels of sotolon [3-hydroxy-4,5-dimethyl-2(5H)
      furanone] and their behavior over time, 86 aged Madeira wines samples (1-25 years
      old), with different sugar concentrations, respectively, 90 g L(-)(1) for Boal,
      110 g L(-)(1) for Malvazia, 25 g L(-)(1) for Sercial, and 65 g L(-)(1) for
      Verdelho varieties, were analyzed. Isolation was performed by liquid-liquid
      extraction with dichloromethane followed by chromatographic analysis by GC-MS.
      The reproducibility of the method was found to be 4.9%. The detection and
      quantification limits were 1.2 and 2.0 microg L(-)(1), respectively. The levels
      of sotolon found ranged from not detected to 2000 microg L(-)(1) for wines
      between 1 and 25 years old. It was observed that during aging, the concentration
      of sotolon increased with time in a linear fashion (r = 0.917). The highest
      concentration of sotolon was found in wines with the highest residual sugar
      contents, considering the same time of storage. The results show that there is a
      strong correlation between sotolon and sugar derivatives: furfural, 5
      methylfurfural, 5-hydroxymethylfurfural, and 5-ethoxymethylfurfural. These
      compounds are also well correlated with wine aging. These findings indicate that
      the kinetics of sotolon formation is closely related with residual sugar
      contents, suggesting that this molecule may come from a component like sugar.

PMID- 15506815
TI  - Conformational states of sunflower (Helianthus annuus) Helianthinin: effect of
      heat and pH.
AB  - The structure and solubility of helianthinin, the most abundant protein of
      sunflower seeds, was investigated as a function of pH and temperature.
      Dissociation of the 11S form (hexamer) into the 7S form (trimer) gradually
      increased with increasing pH from 5.8 to 9.0. High ionic strength (I = 250 mM)
      stabilizes the 11S form at pH > 7.0. Heating and low pH resulted in dissociation
      into the monomeric constituents (2-3S). Next, the 7S and 11S forms of
      helianthinin were isolated and shown to differ in their secondary and tertiary
      structure, and to have denaturation temperatures (T(d)) of 65 and 90 degrees C,
      respectively. Furthermore, the existence of two populations of the monomeric form
      of helianthinin with denaturation temperatures of 65 and 90 degrees C was
      described. This leads to the hypothesis that helianthinin can adopt two different
      conformational states: one with T(d) = 65 degrees C and a second with T(d) = 90
      degrees C.

PMID- 15506816
TI  - Anthocyanin quantification and radical scavenging capacity of Concord, Norton,
      and Marechal Foch grapes and wines.
AB  - The anthocyanin content and the radical scavenging capacity of three non-Vitis
      vinifera grapes (Marechal Foch, Norton, and Concord varieties) were determined.
      Analyses of anthocyanins in the skin (S) and wine (W) of these grape varieties
      were performed by spectrophotometry, HPLC with electrochemical detection, and
      matrix-assisted laser desorption ionization (MALDI). The total anthocyanin
      contents of S samples were 258 +/- 37 mg/100 g of wet weight for Foch, 888 +/- 78
      mg/100 g for Norton, and 326 +/- 5.9 mg/100 g for Concord grapes. The malvidin
      3,5-diglucoside content quantified by HPLC indicated that Norton S had the
      highest amount of the compound (327 +/- 110 mg/100 g). The MALDI mass
      spectrometric analysis indicated an abundance of malvidin glucosides in W of Foch
      grapes and in S and W of Norton grapes and of cyanidin aglycon in S and W of
      Concord grapes. S samples were subjected to a radical scavenging capacity test
      using the 2,2-diphenyl-1-picrylhydrazyl radical and compared to Trolox. The
      radical scavenging capacity for Foch S was 0.78 mM Trolox equiv, that of Concord
      S, 0.80 Trolox equiv, and that of Norton S was highest at 0.95 Trolox equiv. The
      higher concentrations of malvidin 3,5-diglucoside in S of grape varieties were
      associated with greater radical scavenging capacity.

PMID- 15506817
TI  - Varietal differences in phenolic content and antioxidant and antiproliferative
      activities of onions.
AB  - Epidemiological studies have indicated that the consumption of fruits and
      vegetables is associated with a reduced risk for the development of chronic
      diseases, such as cardiovascular disease and cancer. Phytochemicals, including
      phenolics and flavonoids, are suggested to be the major bioactive compounds
      contributing to the health benefits of fruits and vegetables. Onions are a major
      source of dietary flavonoids; however, there may exist varietal differences in
      composition, concentration, and beneficial activities. To characterize these
      differences, shallots and 10 onion (Allium cepa L.) varieties commonly available
      in the United States (Western Yellow, Northern Red, New York Bold, Western White,
      Peruvian Sweet, Empire Sweet, Mexico, Texas 1015, Imperial Valley Sweet, and
      Vidalia) were evaluated for total phenolic and flavonoid contents and antioxidant
      and antiproliferative activities. Shallots contained the highest total phenolic
      content (114.7 +/- 10.0 mg/100 g of sample) among the varieties tested, with a 6
      fold difference observed when compared to the variety with the lowest phenolic
      content (Vidalia, p < 0.05). Western Yellow onion variety exhibited the highest
      total flavonoid content (69.2 +/- 3.7 mg/100 g of onion) of the varieties tested,
      with an 11-fold difference when compared to the variety with the lowest flavonoid
      content (Western White, p < 0.05). Shallots exhibited the highest total
      antioxidant activity (45.5 +/- 2.1 micromol of vitamin C equiv/g of onion),
      followed by Western Yellow, New York Bold, Northern Red, Mexico, Empire Sweet,
      Western White, Peruvian Sweet, Texas 1015, Imperial Valley Sweet, and Vidalia.
      For all varieties, both total phenolic and flavonoid contents were strongly
      correlated with total antioxidant activity (R (2) = 0.9668, p < 0.05; and R (2) =
      0.7033, p < 0.05, respectively). The proliferation of HepG(2) and Caco-2 cells
      was significantly inhibited in a dose-dependent fashion after exposure to the
      Western Yellow, shallots, New York Bold, and Northern Red extracts, with Western
      Yellow, shallots, and New York Bold exhibiting the highest antiproliferative
      activity against HepG(2) cells and New York Bold and Western Yellow exhibiting
      the highest antiproliferative activity against Caco-2 cells. However, the
      varieties of Western White, Peruvian Sweet, Empire Sweet, Mexico, Texas 1015,
      Imperial Valley Sweet, and Vidalia demonstrated weak antiproliferative activity
      against both HepG(2) and Caco-2 cells. These results may influence consumers
      toward purchasing onion varieties exhibiting greater potential health benefits
      and may significantly affect future breeding efforts to enhance onion nutritional
      qualities.

PMID- 15506818
TI  - Metabolic profiling of flavonol metabolites in human urine by liquid
      chromatography and tandem mass spectrometry.
AB  - Twenty-one flavonol metabolites have been identified by LC/ESI-MS/MS in human
      urine, including isomers, after the consumption of cooked onions. Metabolites
      identified include quercetin monoglucuronides, methyl quercetin monoglucuronides,
      a quercetin monoglucuronide sulfate, quercetin diglucuronides, a methyl quercetin
      diglucuronide, quercetin glucoside sulfates, methyl quercetin, quercetin, and
      kaempferol monoglucuronides. The fragmentation patterns of flavonol metabolites
      obtained by MS/MS were distinctive for some isomers, indicating that
      fragmentation patterns may be useful predictors of conjugation position. Two
      isomers of sulfate quercetin glucosides were also found in urine, suggesting that
      many of the quercetin glucosides in onion are absorbed intact and undergo
      metabolism to the sulfate conjugate. Additionally, the interindividual variation
      in urinary quercetin metabolite profiles was determined by comparing the relative
      level of six different quercetin metabolites excreted in the urine of healthy
      volunteers. The ranges of quercetin metabolites excreted were similar among
      volunteers, yet notable differences in the levels of metabolites among
      individuals were observed. This study demonstrates the potential of monitoring
      the range of quercetin metabolites to reveal information on interindividual
      biotransformation capacity in response to dietary manipulations and as a
      biomarker for flavonol consumption.

PMID- 15506819
TI  - Identification of urinary metabolites of the red clover isoflavones formononetin
      and biochanin A in human subjects.
AB  - Dietary supplements manufactured from red clover are widely marketed to provide
      the beneficial health effects of isoflavones without changing the original diet.
      In this study the metabolism of formononetin and biochanin A, the principal
      isoflavones of red clover, was studied in human subjects. Seven women ingested
      four red clover dietary supplements, and the metabolites of the isoflavones were
      identified in their urine samples. The structures of trimethylsilyl derivatives
      of the metabolites were established by GC-MS. New reduced metabolites of
      formononetin (dihydroformononetin and angolensin) and biochanin A
      (dihydrobiochanin A and 6'-hydroxyangolensin) were identified in urine samples
      using authentic reference compounds. Possible metabolic pathways are presented
      for the red clover isoflavones formononetin and biochanin A.

PMID- 15506820
TI  - Effects of protein engineering of canola procruciferin on its physicochemical and
      functional properties.
AB  - The primary structure of Brassica napus procruciferin 2/3a was engineered to
      elucidate structure-function relationships and to improve the functionality of
      cruciferin. The following mutants were constructed: (1) C287T, (2) DeltaII,
      variable region II was deleted; (3) C287T/DeltaII, mutation involving (1) and
      (2); (4) DeltaIV + A1aIV; and (5) DeltaIV + A3IV, variable region IV was replaced
      with variable region IV containing many charged residues from soybean glycinin
      A1aB1b and A3B4 subunits. Differential scanning calorimetry analysis revealed
      that the A1aIV region has a more favorable interaction with the procruciferin
      molecule than does A3IV as well as the original regions. On the basis of heat
      induced precipitation analysis, it was concluded that replacement of the free
      cysteine residue with threonine (C287T) and insertion of charged regions (DeltaIV
      + A1aIV and DeltaIV + A3IV) could lead procruciferin to form soluble aggregates
      after heating. Low solubility was observed in mutants DeltaIV + A3IV, DeltaII,
      and C287T/DeltaII, especially between pH 4 and 6 at mu = 0.08, but not in DeltaIV
      + A1aIV, indicating that the number of acidic amino acid residues and the high
      number of glutamine residues are important factors for solubility at mu = 0.08.
      None of the mutants showed any improvements in emulsifying ability, indicating
      that destabilization and addition of the hydrophilic region are not effective for
      emulsification. The insertion of the A1aIV region in procruciferin made the
      molecule more susceptible to alpha-chymotrypsin.

PMID- 15506821
TI  - Novel low-density lipoprotein (LDL) oxidation model: antioxidant capacity for the
      inhibition of LDL oxidation.
AB  - A novel model of peroxyl radical initiated low-density lipoprotein (LDL)
      oxidation (LDL oxidation model for antioxidant capacity, or LOMAC) was developed
      to assess the free radical scavenging capacity of antioxidants and the extracts
      of natural products. A water-soluble free radical initiator, 2,2'
      azobis(amidinopropane) dihydrochloride, was used at physiological temperature (37
      degrees C) to generate peroxyl radicals to catalyze lipid oxidation of LDL
      isolated from human plasma samples. Headspace hexanal, a major decomposition
      product of LDL oxidation, was measured by a headspace gas chromatograph as an
      indicator of antioxidant capacity of different concentrations of pure
      antioxidants (vitamins C and E) and the extracts of natural products (fresh apple
      phytochemical extracts). All vitamin C and E and apple extract concentrations
      tested resulted in increasing partial suppression and delay of LDL oxidation. On
      the basis of the median effective dose (EC(50)) calculated for each compound or
      extract tested, the LOMAC value of 100 g of apple against LDL oxidation was
      equivalent to 1470 mg of vitamin E or to 402 mg of vitamin C. This study shows
      that the LOMAC assay can be routinely used to analyze or screen antioxidants or
      phytochemical extracts against LDL oxidation to prevent cardiovascular disease.
      The food-specific LOMAC values will be very useful as a new alternative biomarker
      for future epidemiological studies of cardiovascular disease.

PMID- 15506822
TI  - Effect of essential oils on the growth of Fusarium verticillioides and fumonisin
      contamination in corn.
AB  - Essential oils extracted by hydrodistillation from local plants in Benin, western
      Africa, and oil from seeds of the neem tree (Azadirachta indica) were evaluated
      in vitro and in vivo for their efficacy against Fusarium verticillioides
      infection and fumonisin contamination. Fumonisin in corn was quantified using a
      fluorometer and the Vicam method. Oils from Cymbopogon citratus, Ocimum
      basilicum, and Ocimum gratissimum were the most effective in vitro, completely
      inhibiting the growth of F. verticillioides at lower concentrations over 21 days
      of incubation. These oils reduced the incidence of F. verticillioides in corn and
      totally inhibited fungal growth at concentrations of 8, 6.4, and 4.8 microL/g,
      respectively, over 21 days. At the concentration of 4.8 microL/g, these oils did
      not affect significantly fumonisin production. However, a marked reduction of
      fumonisin level was observed in corn stored in closed conditions. The oils
      adversely affected kernel germination at 4.8 microL/g and therefore cannot be
      recommended for controlling F. verticillioides on stored corn used as seeds, when
      used at this concentration. The oil of neem seeds showed no inhibitory effect but
      rather accelerated the growth of F. verticillioides.

PMID- 15506823
TI  - Origin and mechanistic pathways of formation of the parent furan--a food
      toxicant.
AB  - Studies performed on model systems using pyrolysis-GC-MS analysis and (13)C
      labeled sugars and amino acids in addition to ascorbic acid have indicated that
      certain amino acids such as serine and cysteine can degrade and produce
      acetaldehyde and glycolaldehyde that can undergo aldol condensation to produce
      furan after cyclization and dehydration steps. Other amino acids such as aspartic
      acid, threonine, and alpha-alanine can degrade and produce only acetaldehyde and
      thus need sugars as a source of glycolaldehyde to generate furan. On the other
      hand, monosaccharides are also known to undergo degradation to produce both
      acetaldehyde and glycolaldehyde; however, (13)C-labeling studies have revealed
      that hexoses in general will mainly degrade into the following aldotetrose
      derivatives to produce the parent furan-aldotetrose itself, incorporating the C3
      C4-C5-C6 carbon chain of glucose (70%); 2-deoxy-3-ketoaldotetrose; incorporating
      the C1-C2-C3-C4 carbon chain of glucose (15%); and 2-deoxyaldotetrose,
      incorporating the C2-C3-C4-C5 carbon chain of glucose (15%). Furthermore, it was
      also proposed that under nonoxidative conditions of pyrolysis, ascorbic acid can
      generate the 2-deoxyaldotetrose moiety, a direct precursor of the parent furan.
      In addition, 4-hydroxy-2-butenal-a known decomposition product of lipid
      peroxidation-was proposed as a precursor of furan originating from
      polyunsaturated fatty acids. Among the model systems studied, ascorbic acid had
      the highest potential to produce furan, followed by glycolaldehyde/alanine >
      erythrose > ribose/serine > sucrose/serine > fructose/serine > glucose/cysteine.

PMID- 15506824
TI  - Acrylamide formation from asparagine under low-moisture Maillard reaction
      conditions. 1. Physical and chemical aspects in crystalline model systems.
AB  - The formation of acrylamide in crystalline model systems based on asparagine and
      reducing sugars was investigated under low-moisture reaction conditions. The
      acrylamide amounts were correlated with physical changes occurring during the
      reaction. Molecular mobility of the precursors turned out to be a critical
      parameter in solid systems, which is linked to the melting behavior and the
      release of crystallization water of the reaction sample. Heating binary mixtures
      of asparagine monohydrate and anhydrous reducing sugars led to higher acrylamide
      amounts in the presence of fructose compared to glucose. Differential scanning
      calorimetry measurements performed in open systems indicated melting of fructose
      at 126 degrees C, whereas glucose and galactose fused at 157 and 172 degrees C,
      respectively. However, glucose was the most reactive and fructose the least
      efficient sugar in anhydrous liquid systems, indicating that at given molecular
      mobility the chemical reactivity of the sugar was the major driver in acrylamide
      formation. Furthermore, reaction time and temperature were found to be covariant
      parameters: acrylamide was preferably formed by reacting glucose and asparagine
      at 120 degrees C for 60 min, whereas 160 degrees C was required at shorter
      reaction time (5 min). These results suggest that, in addition to the chemical
      reactivity of ingredients, their physical state as well as reaction temperature
      and time would influence the formation of acrylamide during food processing.

PMID- 15506825
TI  - Detection of Tumor Markers Including Carcinoembryonic Antigen, APC, and Cyclin D2
      in Fine-Needle Aspiration Fluid of Breast.
AB  - Context.-The traditional triple test for breast cancer diagnosis is physical
      examination, mammography, and aspiration cytology. However, the accuracy of
      mammography on young women with nonatrophied breasts is poor compared with that
      for women older than 50 years, and additional methods for diagnosis of breast
      cancer are needed.Objective.-To investigate whether carcinoembryonic antigen
      (CEA), CA 15-3, and CA 125 concentrations in breast aspiration fluid are useful
      as breast cancer biochemical markers and whether APC and cyclin D2 gene promoter
      hypermethylation could be regarded as a breast cancer molecular marker.Design.
      CEA, CA 15-3, and CA 125 concentrations were measured, and methylation status of
      the APC gene promoter 1A and the promoter region of the cyclin D2 gene were
      analyzed using a methylation-specific polymerase chain reaction assay of ex vivo
      breast aspiration fluid obtained from 49 samples of excised breast
      tissue.Setting.-The specimens were collected during a 1-year period in the
      tertiary care teaching hospital in Seoul, Korea.Patients.-Forty-nine patients
      with breast masses were surgically treated. Thirty-four patients had breast
      cancer, and 15 had benign breast disease.Results.-Aspiration fluid CEA
      concentrations were significantly higher in breast cancer cases than in cases of
      benign breast disease (mean, 69.90 ng/mg protein vs 0.68 ng/mg protein,
      respectively; P < .001). At 90% specificity of the assay (CEA, 2.13 ng/mg
      protein), the corresponding sensitivity for breast cancer detection was 62%,
      according to the receiver operating characteristic curve drawn. The APC gene
      promoter 1A and the promoter region of the cyclin D2 gene were methylated in 42%
      (14/33) and 70% (23/33) of the breast cancer aspiration fluid samples,
      respectively. A cumulative incidence of methylation of these 2 genes was 85%
      (28/33). The APC and cyclin D2 gene promoters were both unmethylated in the
      aspiration fluids from 19 women with nonmalignant breast disease.Conclusions.
      Breast aspiration fluid CEA concentration and the methylation of the APC gene
      promoter 1A and the promoter region of the cyclin D2 gene can be used as tumor
      markers to overcome some of the limitations of aspiration cytology. In
      combination with the mammogram and physical examination, assays for these markers
      could be used to help determine a definitive diagnosis when cytologic results are
      suspicious for malignancy.

PMID- 15506826
TI  - Bone Morphogenetic Proteins Are Expressed by Both Bone-Forming and Non-Bone
      Forming Lesions.
AB  - Context.-Bone morphogenetic proteins (BMPs) are thought to be responsible for
      bone formation; they cause bone to form in soft tissues and are clinically used
      in helping fracture union or tumor reconstructions. Skeletal metastases from
      epithelial tumors may be either bone-forming (blastic) or non-bone-forming
      (lytic).Objective.-We studied the expression of BMPs in a variety of primary and
      secondary lesions of bone (both bone-forming and non-bone-forming) to determine
      if there was a consistent relationship between bone formation and BMP
      expression.Design.-We compared a bone-forming lesion (fibrous dysplasia) with a
      non-bone-forming lesion (desmoid tumor), using reverse transcription-polymerase
      chain reaction, Northern blot analysis, and immunohistochemistry to detect BMPs.
      We also studied a number of non-bone-forming secondary lesions (carcinomas that
      formed lytic metastases to the skeleton) and found BMP production in most of
      these tumors.Results.-We found that BMPs were expressed in both bone-forming and
      non-bone-forming benign musculoskeletal lesions. In the first part of the study,
      BMPs were found in both fibrous dysplasia and desmoid tumors. Bone morphogenetic
      proteins were also expressed by several tumors. In the next part of the study
      (paraffin-embedded tissue), BMPs were expressed by a variety of tumors,
      irrespective of the radiological nature (blastic or lytic) of their
      metastases.Conclusions.-We conclude that BMP production alone cannot explain bone
      formation, and other factors either alone or in combination may be responsible
      for blastic metastases to the skeleton and for bone formation by primary bone
      lesions, such as fibrous dysplasia.

PMID- 15506827
TI  - Loss of distinctive features and a broader pattern of priming in Alzheimer's
      disease.
AB  - The results of 2 experiments support the contention that patients with
      Alzheimer's disease (AD) show a relative loss of the semantic features that
      distinguish concepts from one another and that the representations of pairs of
      concepts consequently share a larger proportion of their associated features in
      AD than in normal aging. In Experiment 1, AD patients listed fewer features for a
      set of concepts than did healthy older adults and were more deficient at listing
      features if the features were distinctive to particular concepts than if they
      were shared by multiple concepts. In Experiment 2, AD patients showed online
      priming at levels of relatedness at which healthy older adults did not.

PMID- 15506828
TI  - Executive functioning, memory, and learning in phenylketonuria.
AB  - The executive deficit hypothesis of treated phenylketonuria (PKU) suggests that
      dopaminergic depletion in the lateral prefrontal cortex leads to selective
      executive impairment. This was examined by comparing adults with PKU on a
      lifelong diet with a matched healthy control group. Those with PKU were impaired
      on selective and sustained attention, working memory (Self-Ordered Pointing), and
      letter fluency. However, they failed to show differential sensitivity to
      increased cognitive load on the attentional and working memory tasks, and they
      did not differ significantly on the remaining executive tasks (rule finding,
      inhibition, and multitasking). Nor did they differ significantly on recall or
      recognition memory. Overall, the findings provided little support for the
      executive deficit hypothesis. A possible explanation in terms of slowed
      information processing speed is explored.

PMID- 15506829
TI  - A meta-analytic review of verbal fluency performance in patients with traumatic
      brain injury.
AB  - A meta-analysis of 30 studies with 1,269 participants was conducted to
      investigate the sensitivity of tests of verbal fluency to the presence of
      traumatic brain injury (TBI). As has been found for patients with focal frontal
      lobe injuries (but not for patients with focal temporal lobe lesions), TBI
      patients were comparably impaired on tests of phonemic and semantic fluency. The
      phonemic fluency deficit could not be accounted for by patients' level of
      premorbid or current verbal IQ and was also substantially (although not
      significantly) in excess of the deficit on a measure of psychomotor speed.
      Phonemic fluency was also significantly more sensitive to the presence of TBI
      than was the Wisconsin Card Sorting Test.

PMID- 15506831
TI  - Motor areas beyond motor performance: deficits in serial prediction following
      ventrolateral premotor lesions.
AB  - Previous functional MRI findings have indicated that a premotor-parietal network
      is involved in the perceptual processing of sequential information. Given that
      premotor functions have traditionally been restricted to behaviors requiring
      motor or sensorimotor computations, the goal of the present patient study was to
      further investigate whether the lateral premotor cortex is critical in purely
      perceptual sequencing. Patients with either ventral premotor or inferior parietal
      lesions, in addition to patients with prefrontal lesions and age- and gender
      matched healthy controls, were tested during the processing of temporal, object
      specific, and spatial sequences. Results revealed that premotor patients as well
      as parietal patients showed significantly higher error rates than did healthy
      controls on all sequence tasks. In contrast, prefrontal patients showed no
      behavioral deficits. These findings support the significance of the ventrolateral
      premotor cortex, in addition to parietal areas, in nonmotor (attentional)
      functions.

PMID- 15506832
TI  - Inter- and intraindividual variability in recognition memory: effects of aging
      and estrogen use.
AB  - Traditionally, studies of cognitive aging have focused on comparing the average
      performance of younger and older adults, whereas variability around the mean has
      been attributed to task-irrelevant noise. The present study examined the
      hypothesis that variability in memory performance increases with age and that
      estrogen helps temper age-related increases in variability. Postmenopausal
      estrogen users, estrogen and progestin (est + prog) users, and nonusers, as well
      as younger women, completed 16 blocks of an item-source memory task. Older women
      showed greater variability than younger women on measures of dispersion and
      consistency. Estrogen users, but not est + prog users, performed more
      consistently than nonusers. Overall, age-related increases in variability
      differed with the type of variability measured, and estrogen use, but not est +
      prog use, appeared to reduce age-related increases in at least 1 form of
      variability.

PMID- 15506830
TI  - Neuropsychological correlates of diffusion tensor imaging in schizophrenia.
AB  - Patients with schizophrenia (n = 41) and healthy comparison participants (n = 46)
      completed neuropsychological measures of intelligence, memory, and executive
      function. A subset of each group also completed magnetic resonance diffusion
      tensor imaging (DTI) studies (fractional anisotropy and cross-sectional area) of
      the uncinate fasciculus (UF) and cingulate bundle (CB). Patients with
      schizophrenia showed reduced levels of functioning across all neuropsychological
      measures. In addition, selective neuropsychological-DTI relationships emerged.
      Among patients but not controls, lower levels of declarative-episodic verbal
      memory correlated with reduced left UF, whereas executive function errors related
      to performance monitoring correlated with reduced left CB. The data suggested
      abnormal DTI patterns linking declarative-episodic verbal memory deficits to the
      left UF and executive function deficits to the left CB among patients with
      schizophrenia.

PMID- 15506833
TI  - Cognitive strengths and weaknesses in children and adolescents homozygous for the
      galactosemia Q188R mutation: a descriptive study.
AB  - Children and adolescents (n = 25) with galactosemia homozygous for the common
      Q188R mutation (substitution of glutamine codon 188 with arginine) were group
      matched for sex and age with healthy control participants (n = 20). Participants
      were administered an abbreviated neuropsychological battery by a doctoral-level
      psychologist. Results indicate that children and adolescents with galactosemia
      function generally within the low average IQ range, with a small standard
      deviation (indicating a relatively homogeneous IQ profile), and have many
      features suggestive of left-hemisphere dysfunction. Word retrieval difficulties
      are a primary component of the galactosemia profile. In addition, participants
      with galactosemia have less well-developed executive functions. Child and
      parental reports of behavioral symptoms differ; parents reported that their
      children had more internalizing symptoms than the children with galactosemia self
      reported. Cognitive complications in galactosemia appear to emerge even in well
      treated children.

PMID- 15506834
TI  - Deficits of organizational strategy and visual memory in obsessive-compulsive
      disorder.
AB  - This study was conducted to investigate the deficits of organizational strategy
      and visual memory in obsessive-compulsive disorder (OCD). Thirty OCD patients and
      30 healthy controls aged 20-35 years participated. The Maudsley Obsessive
      Compulsive Inventory, Beck Anxiety Inventory, Wechsler Adult Intelligence Scale,
      and Rey-Osterrieth Complex Figure (ROCF) test were administered to participants.
      The authors scored ROCF performances using the Boston Qualitative Scoring System.
      The OCD patients showed poorer planning ability and higher fragmentation than did
      healthy controls when copying the ROCF, and they showed even poorer performances
      in the immediate and delayed recall conditions. The authors found that the
      Organization score in the copy condition mediated the difference between the OCD
      group and the healthy group in immediate recall. The direct effect of diagnosis
      (OCD or healthy) on the immediate recall condition of the ROCF was also
      significant. This study indicates that people with OCD have poor memory function
      and organizational deficits.

PMID- 15506835
TI  - Spatial working memory deficits in children at ages 3-4 who were low birth
      weight, preterm infants.
AB  - The aim of this study was to investigate attention and perceptual and spatial
      working memory abilities in preterm, low birth weight preschool children without
      evident brain disorders as determined by normal cerebral ultrasound findings and
      normal motor development. The authors evaluated 19 preterm and 19 typically
      developing children who were matched for IQ and chronological age. Results
      indicated that children born prematurely without major neurological deficits and
      with a normal cognitive level may have specific difficulty in sustained
      attention, visuospatial processing, and spatial working memory when evaluated at
      ages 3-4. This finding is relevant for understanding the qualitative aspects of
      cognitive development in preterm children and the neurobiological substrate
      underlying this development.

PMID- 15506836
TI  - Impaired higher order implicit sequence learning on the verbal version of the
      serial reaction time task in patients with Parkinson's disease.
AB  - Although neuroimaging studies have strongly implicated basal ganglia involvement
      in implicit sequence learning, serial reaction time (SRT) studies with
      Parkinson's disease (PD) patients have yielded mixed results. The present
      research sought to examine the ability of people with PD to implicitly learn
      sequences with different sequential structures and to objectively assess explicit
      knowledge. A version of the SRT task that reduces motor demands was used to
      compare 19 patients with PD but not dementia and 37 matched controls. PD patients
      showed less implicit sequence-specific learning for both sequences and reduced
      response time improvement over sequential trials for the more complex sequence. A
      closer examination revealed that the deficit involved higher order sequential
      associations as well as the learning of pairwise information.

PMID- 15506838
TI  - Neuroanatomical basis in the temporal lobes for processing living things.
AB  - Category-specific impairment in living things was examined in patients with
      temporal lobe damage to investigate whether specific neuroanatomical regions
      could be identified in processing the knowledge of specific categories. Tasks
      involving more effortful retrieval naming and less effortful attribute judgment
      were administered to 3 groups of patients with either bilateral, unilateral left,
      or unilateral right temporal lobe damage. Category-specific impairment in living
      things was observed for patients with unilateral or bilateral damage, results
      that are consistent with previous findings. Depending on its site and extent, the
      damage in the temporal lobe might lead to deficits in processing or loss of
      semantic knowledge for living things. Therefore, intact category-specific
      semantic processes may involve associations among different neural substrates in
      the temporal lobe.

PMID- 15506837
TI  - Retrograde amnesia in dementia: comparison of HIV-associated dementia,
      Alzheimer's disease, and Huntington's disease.
AB  - Remote memory was assessed in persons with HIV-associated dementia (HIV-D),
      probable Alzheimer's disease (AD), and Huntington's disease (HD) and in healthy
      controls. The clinical groups were similar in overall dementia severity. Each
      clinical group exhibited impairments on remote memory tests relative to controls;
      however, temporally graded memory loss with selective preservation of older
      information was observed in the AD group but not the HD or HIV-D group. Analysis
      of cued retrieval indicated a preferential cuing benefit for the HIV-D and HD
      groups relative to the AD group. The similar pattern of remote memory performance
      demonstrated by the HIV-D and HD groups is a novel finding and suggests a
      subcortically mediated retrograde amnesia in HIV-D. The temporally graded pattern
      and the abnormal cued retrieval performance in the AD group are consistent with a
      consolidation deficit associated with extrahippocampal (cortical) and hippocampal
      damage.

PMID- 15506839
TI  - Splenial lesions lead to supramodal target detection deficits.
AB  - Patients with lesions of the splenium showed higher validity effects of
      visuospatial cues than did patients with partial lesions of the corpus callosum
      anterior to the splenium and control participants. Many of the patients tested
      had also shown a left-ear suppression for consonant-vowel syllables in a previous
      dichotic listening study. The authors interpret these parallel findings as
      evidence for the disruption of signals that normally alert the individual to the
      presence of behaviorally relevant stimuli, possibly originating in the
      temporoparietal junction area. After splenial lesions, these signals may not
      reach the contralateral hemisphere, leading to supramodal deficits in target
      detection, especially under distracting conditions.

PMID- 15506840
TI  - Alpha event-related desynchronization preceding a go/no-go task: a high
      resolution EEG study.
AB  - The authors delineated the time evolution of alpha event-related
      desynchronization over human frontal, parietal, and primary sensorimotor areas
      during the expectancy of a go/no-go task. The main issue under investigation was
      whether anticipatory processes impinged upon cortical areas in sequential or
      parallel mode. Compared with the control condition, in the experimental condition
      there was an Alpha 1 desynchronization over the central midline, an Alpha 2
      desynchronization increasing over primary sensorimotor areas, and an Alpha 3
      desynchronization increasing in parallel over bilateral primary sensorimotor
      areas. These processes had different temporal features. Results disclose an
      anticipatory activity of central midline areas and primary sensorimotor areas in
      both parallel and sequential modes. This reflects an adaptive, energy-consuming
      strategy rather than an economic waiting for the go stimulus.

PMID- 15506841
TI  - Quantitative measurement of cortical surface features in localization-related
      temporal lobe epilepsy.
AB  - Differences in cortical surface features between healthy controls (n = 48) and
      patients with temporal lobe epilepsy (n = 46), ages 14-59, were characterized by
      means of advanced quantitative MRI processing techniques. Cortical surface
      features of interest included gyral and sulcal curvature, cortical depth, and
      total cortical surface area. Epilepsy patients and controls differed on measures
      of gyrification; the abnormalities generalized despite the focal nature of the
      primary epileptic process. Changes in cortical surface features were associated
      with increasing chronological age in both groups. Abnormalities in gyrification
      were associated with cognitive performance and with other morphometric
      measurements (e.g., surface cerebral spinal fluid). These findings are related to
      the literature regarding morphometric changes associated with temporal lobe
      epilepsy and normal aging.

PMID- 15506842
TI  - Sex-linked differences in the anatomy of the perisylvian language cortex: a
      volumetric MRI study of gray matter volumes.
AB  - Perisylvian regions important for auditory processing include Heschl's gyrus
      (HG), the planum temporale (PT), the posterior superior temporal gyrus (pSTG),
      and the posterior ascending ramus (PAR). Sex-linked differences in language
      functions and anatomy have been suggested. To examine sex-linked differences, the
      authors used MRI to measure HG, PT, pSTG, and PAR volumes. Sex differences were
      found in right HG and right pSTG volumes but not in the left volumes of these
      structures. For the PT, there were sex differences in asymmetry; women exhibited
      leftward asymmetry of the PT, whereas men did not exhibit PT asymmetry. These
      findings suggest that there are sex-linked differences in the anatomy of primary
      and association auditory cortices.

PMID- 15506843
TI  - Verbal dichotic listening and manual performance in children with congenital
      unilateral brain lesions.
AB  - The authors assessed manual performance and verbal dichotic listening performance
      in 16 epilepsy-free children with congenital unilateral brain lesions and normal
      IQ to investigate cerebral reorganization. In all children, the paretic hand had
      fair grip function, but reaction times were impaired, and cerebral reorganization
      of hand function in those with right hemiplegia was shown by the high incidence
      of pathological left-handedness. The dichotic listening results showed that most
      children with left lesions had a left ear advantage significantly related to the
      extent of brain damage. This finding suggests that extent of cortical damage and
      presence of thalamic involvement, irrespective of neuropathology, are the primary
      factors inducing rightward cerebral language reorganization in children with
      unilateral congenital brain lesions.

PMID- 15506845
TI  - Implications of work and community demands and resources for work-to-family
      conflict and facilitation.
AB  - Based on a differential salience approach, this article examines the combined
      effects of work and community demands and resources on work-to-family conflict
      and facilitation. The study uses information from 2,507 employed respondents from
      the 1995 National Survey of Midlife Development in the United States. The
      findings indicate that work demands are relatively strongly related to work-to
      family conflict, whereas work resources are relatively more important in relation
      to work-to-family facilitation. Social incoherence and friend demands are
      positively related to work-to-family conflict, whereas sense of community and
      support from friends have positive effects on facilitation. Community resources
      also show weak amplifying effects on some of the positive relationships between
      work resources and work-to-family facilitation. The findings provide modest
      support for the hypotheses.

PMID- 15506844
TI  - Puzzling thoughts for H. M.: can new semantic information be anchored to old
      semantic memories?
AB  - Researchers currently debate whether new semantic knowledge can be learned and
      retrieved despite extensive damage to medial temporal lobe (MTL) structures. The
      authors explored whether H. M., a patient with amnesia, could acquire new
      semantic information in the context of his lifelong hobby of solving crossword
      puzzles. First, H. M. was tested on a series of word-skills tests believed
      important in solving crosswords. He also completed 3 new crosswords: 1 puzzle
      testing pre-1953 knowledge, another testing post-1953 knowledge, and another
      combining the 2 by giving postoperative semantic clues for preoperative answers.
      From the results, the authors concluded that H. M. can acquire new semantic
      knowledge, at least temporarily, when he can anchor it to mental representations
      established preoperatively.

PMID- 15506846
TI  - The relationships among part-time work, work-family interference, and well-being.
AB  - The authors investigated the effect of part-time work on work-family interference
      and well-being among 160 part-time and 29 full-time employed mothers (with a
      partner) working at 2 insurance companies in the Netherlands. The authors
      controlled for working part time as a strategy for reducing work-family imbalance
      and found that part-time work was associated with a lower level of work-to-family
      interference. Also, high levels of work-family interference were associated with
      diminished well-being. Work-to-family interference played a mediating role in the
      relationship between part-time work and well-being. Results indicate that part
      time jobs can enhance the work-family balance not only for those explicitly
      choosing part-time employment as a means to reduce work-family imbalance but also
      for other employees.

PMID- 15506847
TI  - Job strain, job insecurity, and health: rethinking the relationship.
AB  - Job strain (high demands and low control) is a widely used measure of work
      stress. The authors introduce a new way of looking at work stress by combining
      job strain with job insecurity, a combination increasingly prevalent in
      contemporary economies, using data from a cross-sectional survey (N = 1,188) of
      mid-aged Australian managers and professionals. Those reporting both strain and
      insecurity showed markedly higher odds for mental and physical health problems
      (depression: odds ratio [OR] 13.88, 95% confidence interval [CI] 5.67-34.01;
      anxiety: OR 12.88, CI 5.12-32.39; physical health problems: OR 3.97, CI 1.72
      9.16; and poor self-rated health: OR 7.12, CI 2.81-18.01). Job strain and
      insecurity showed synergistic associations with health, and employees
      experiencing both could be at heightened health risk.

PMID- 15506848
TI  - Child health: a legitimate business concern.
AB  - This article reviews evidence substantiating the relationship between child
      health and business outcomes and evaluates literature regarding organizational
      interventions that benefit child health and reduce associated costs. The review
      focuses on 4 family-friendly initiatives, including prenatal programs, lactation
      programs, sick child care, and flexible working arrangements, and considers 4
      business outcomes, specifically health care costs, face time, productive time,
      and employer attractiveness. Limitations of previous research are discussed, and
      preventive and reactive models of the relationship between child health and
      business outcomes are developed as guides for future research.

PMID- 15506849
TI  - Job strain or healthy work: a question of task design.
AB  - Objectively evaluated task requirements were used to classify jobs causing high
      strain, low strain, and jobs conducive to personal development. Effects of these
      job characteristics on psychophysiological outcomes were tested in 241 employees
      by using 24-hr ambulatory assessment of blood pressure (BP), heart rate, and
      mood. Self-reports about job characteristics showed that employees working in
      jobs conducive to personal development perceived the highest job demands and
      decision latitude. They also showed a healthy cardiovascular behavior with
      increased diastolic BP at work and its strong unwinding at night. Although self
      reports about job characteristics did not differ between low- and high-strain
      jobs, employees exposed to high-strain jobs had higher systolic and diastolic BP
      during work and more often a disturbed relaxation ability.

PMID- 15506850
TI  - Explaining potential antecedents of workplace social support: reciprocity or
      attractiveness?
AB  - Effects of social support are an important topic in occupational stress theories
      and research, yet little is known about support's potential antecedents. Based on
      reciprocity theory, the authors hypothesized that the social support received is
      related to the extent the employee performs organizational citizenship behaviors
      directed at individuals and to one's social competence; based on the notion of
      personal attraction, the authors hypothesized that employees' physical
      attractiveness and sense of humor would be associated with the amount of social
      support received. In a survey of 123 high school employees and separate ratings
      of their attractiveness, reciprocity variables were related but attraction
      variables were not related to social support availability. Further research
      should examine reciprocity in predicting social support.

PMID- 15506852
TI  - Apparatus exposure produces profound declines in conditioned nictitating-membrane
      responses to discrete conditioned stimuli by the rabbit (Oryctolagus cuniculus).
AB  - The present experiments demonstrated that in the rabbit (Oryctolagus cuniculus)
      nictitacing-membrane (NM) preparation, exposure to the experimental apparatus
      produces profound declines in conditioned responding to a discrete conditioned
      stimulus (CS; Experiments 1, 2A, and 3). Moreover, this decremental effect is at
      most attenuated in only a minor way when the unconditioned stimulus (US) is
      presented during exposure to the apparatus (Experiment 2B). Controls for
      retention loss (Experiments 1 and 3) and for handling and placement in a
      different context (Experiment 3) did not produce significant declines in
      responding. These findings challenge theories of extinction that rely primarily
      on context-US associations but are more consistent with theories that assume
      context-CS-US associations.

PMID- 15506853
TI  - Control of variation by reward probability.
AB  - Two bar-press experiments with rats tested the rule that reducing expectation of
      reward increases the variation from which reward selects. Experiment 1 used a
      discrete-trial random-interval schedule, with trials signaled by light or sound.
      One signal always ended with reward; the other signal ended with reward less
      often. The 2 signals were randomly mixed. Bar-press duration (how long the bar
      was held down) varied more during the signal with the lower probability of
      reward. Experiment 2 closely resembled Experiment 1 but used a random-ratio
      schedule rather than a random-interval schedule. Again, bar-press duration varied
      more during the signal with the lower probability of reward. The results support
      the rule--the first well-controlled comparisons to do so.

PMID- 15506854
TI  - Outcome pre- and postexposure effects: retention interval interacts with primacy
      and recency.
AB  - Effects of outcome-alone pretraining and posttraining exposure were investigated
      in conditioned suppression experiments conducted within a sensory preconditioning
      preparation with rats. Experiment 1 found that interference by outcome
      postexposure was stronger than that by outcome preexposure, suggesting a recency
      effect. Experiment 2 found that after a long retention interval, outcome
      preexposure produced more interference than outcome postexposure, suggesting a
      shift from recency to primacy with increasing retention interval. Experiment 3
      showed that presentation of a priming stimulus that had been embedded within the
      earlier phase of treatment also caused a shift from recency to primacy. These
      results suggest that, at least in a sensory preconditioning paradigm,
      retrievability of outcome-alone exposure memory is an important determinant of
      any outcome-alone exposure effect.

PMID- 15506855
TI  - The conditions for temporal tracking under interval schedules of reinforcement.
AB  - On many cyclic-interval schedules, animals adjust their postreinforcement pause
      to follow the interval duration (temporal tracking). Six pigeons were trained on
      a series of square-wave (2-valued) interval schedules (e.g., 12 fixed-interval
      [FI] 60, 4 FI 180). Experiment 1 showed that pigeons track square-wave schedules,
      except those with a single long interval per cycle. Experiments 2 and 3
      established that tracking and nontracking are learned and both can transfer from
      one cyclic schedule to another. Experiment 4 demonstrated that pigeons track a
      schedule with a single short interval per cycle, suggesting that a dual process-
      cuing and tracking--is necessary to explain behavior on these schedules. These
      findings suggest a potential explanation for earlier results that reported a
      failure to track square-wave schedules.

PMID- 15506856
TI  - Assessments of changes in the effective salience of stimulus elements as a result
      of stimulus preexposure.
AB  - Rats received exposure to 3 flavor compounds, AX and BX, presented in
      alternation, and CX, presented on a separate block of trials. The hypothesis that
      this treatment would leave B effectively more salient than C was tested in 3
      ways. Experiment 1 showed that the unconditioned response evoked by B was
      stronger than that evoked by C. Experiment 2 showed that B was more effective
      than C when used as a reinforcer in a sensory preconditioning procedure.
      Experiment 3 showed that B was learned about more readily than C as a conditioned
      stimulus in flavor aversion conditioning. Alternating preexposure to 2 similar
      stimuli may protect their distinctive features from the loss of salience normally
      produced by nonreinforced exposure to a stimulus.

PMID- 15506857
TI  - Is the context shift effect a case of retrieval failure? The effects of retrieval
      enhancing treatments on forgetting under altered stimulus conditions in rats.
AB  - This series of experiments sought to clarify the role of retrieval failure in
      forgetting that results from a change in context between training and testing
      (the context shift effect [CSE]). Because spontaneous forgetting (SF) is
      generally considered to reflect a retrieval failure, the effects of three
      manipulations known to alleviate SF were examined on forgetting due to an
      explicit shift in context at a short delay (24 hr). Pretest exposure to a
      reminder treatment involving the reinforcer from training (Experiment 1), pretest
      amphetamine administration (Experiment 2), and overtraining (Experiment 3)
      alleviated both SF and the CSE, supporting the view that the CSE reflects a
      retrieval deficit. Implications for the context change account of SF are
      discussed.

PMID- 15506858
TI  - Transformational and transactional leadership: a meta-analytic test of their
      relative validity.
AB  - This study provided a comprehensive examination of the full range of
      transformational, transactional, and laissez-faire leadership. Results (based on
      626 correlations from 87 sources) revealed an overall validity of .44 for
      transformational leadership, and this validity generalized over longitudinal and
      multisource designs. Contingent reward (.39) and laissez-faire (-.37) leadership
      had the next highest overall relations; management by exception (active and
      passive) was inconsistently related to the criteria. Surprisingly, there were
      several criteria for which contingent reward leadership had stronger relations
      than did transformational leadership. Furthermore, transformational leadership
      was strongly correlated with contingent reward (.80) and laissez-faire (-.65)
      leadership. Transformational and contingent reward leadership generally predicted
      criteria controlling for the other leadership dimensions, although
      transformational leadership failed to predict leader job performance.

PMID- 15506859
TI  - Crossover of marital dissatisfaction during military downsizing among Russian
      army officers and their spouses.
AB  - This study examined mechanisms of strain crossover within couples and the
      moderating role of gender. Data were collected at a time of military downsizing
      from a sample of 1,250 Russian army officers and their spouses. The authors
      tested a model that incorporated 3 mechanisms for the crossover of marital
      dissatisfaction among dual-earner couples. The model provided support for 2
      suggested crossover mechanisms: direct reactions of crossover and indirect
      mediated effects through social undermining. Strong evidence was also provided
      for gender asymmetry in the crossover process. Marital dissatisfaction crossed
      over from husbands to wives but not vice versa, and social undermining behavior
      played a role in the process of crossover of marital dissatisfaction for husbands
      but not for wives.

PMID- 15506860
TI  - Dependent effect sizes in meta-analysis: incorporating the degree of
      interdependence.
AB  - In the present article, a commonly used meta-analytic procedure for handling
      dependent effect sizes from a single sample was examined, and 2 revised
      procedures that estimate and incorporate the degree of interdependence were
      proposed. The authors' simulation results reveal that the commonly used procedure
      that averages the effect sizes from a single sample (denoted as the samplewise
      procedure) underestimates the degree of heterogeneity. The proposed variations
      are less biased than the samplewise procedure in estimating the degree of
      heterogeneity in most of the situations that we examined. Future directions to
      further improve the procedures for handling dependent effect sizes from a single
      sample are discussed.

PMID- 15506861
TI  - Alpha's standard error (ASE): an accurate and precise confidence interval
      estimate.
AB  - This research presents the inferential statistics for Cronbach's coefficient
      alpha on the basis of the standard statistical assumption of multivariate
      normality. The estimation of alpha's standard error (ASE) and confidence
      intervals are described, and the authors analytically and empirically investigate
      the effects of the components of these equations. The authors then demonstrate
      the superiority of this estimate compared with previous derivations of ASE in a
      separate Monte Carlo simulation. The authors also present a sampling error and
      test statistic for a test of independent sample alphas. They conclude with a
      recommendation that all alpha coefficients be reported in conjunction with
      standard error or confidence interval estimates and offer SAS and SPSS
      programming codes for easy implementation.

PMID- 15506862
TI  - Feedback specificity, learning opportunities, and learning.
AB  - Although increasing feedback specificity is generally beneficial for immediate
      performance, it can undermine certain aspects of the learning needed for later,
      more independent performance. The results of the present transfer experiment
      demonstrate that the effects of increasing feedback specificity on learning
      depended on what was to be learned, and these effects were partially mediated
      through the opportunities to learn how to respond to different task conditions
      during practice. More specific feedback was beneficial for learning how to
      respond to good performance and detrimental for learning how to respond to poor
      performance. The former relationship was partially mediated by feedback
      specificity's effect on learning opportunities during practice. The results have
      implications for designing feedback interventions and training to maximize the
      learning of various aspects of a task.

PMID- 15506863
TI  - Complementary and supplementary fit: a theoretical and empirical integration.
AB  - Complementary and supplementary fit represent 2 distinct traditions within the
      person-environment fit paradigm. However, these traditions have progressed in
      parallel but separate streams. This article articulates the theoretical
      underpinnings of the 2 traditions, using psychological need fulfillment and value
      congruence as prototypes of each tradition. Using a sample of 963 adult employees
      ranging from laborers to executives, the authors test 3 alternative conceptual
      models that examine the complementary and supplementary traditions. Results show
      that an integrative model dominates the other two, such that both traditions
      simultaneously predict outcomes in different ways.

PMID- 15506864
TI  - The big five personality traits and individual job performance growth
      trajectories in maintenance and transitional job stages.
AB  - This study extends the literature on personality and job performance through the
      use of random coefficient modeling to test the validity of the Big Five
      personality traits in predicting overall sales performance and sales performance
      trajectories--or systematic patterns of performance growth--in 2 samples of
      pharmaceutical sales representatives at maintenance and transitional job stages
      (K. R. Murphy, 1989). In the maintenance sample, conscientiousness and
      extraversion were positively associated with between-person differences in total
      sales, whereas only conscientiousness predicted performance growth. In the
      transitional sample, agreeableness and openness to experience predicted overall
      performance differences and performance trends. All effects remained significant
      with job tenure statistically controlled. Possible explanations for these
      findings are offered, and theoretical and practical implications of findings are
      discussed.

PMID- 15506865
TI  - Affect networks: a structural analysis of the relationship between work ties and
      job-related affect.
AB  - The relationship between organizational networks and employees' affect was
      examined in 2 organizations. In Study 1, social network analysis of work ties and
      job-related affect for 259 employees showed that affect converged within work
      interaction groups. Similarity of affect between employees depended on the
      presence of work ties and structural equivalence. Affect was also related to the
      size and density of employees' work networks. Study 2 used a 10-week diary study
      of 31 employees to examine a merger of 2 organizational divisions and found that
      negative changes in employees' affect were related to having fewer cross
      divisional ties and to experiencing greater reductions in network density. The
      findings suggest that affect permeates through and is shaped by organizational
      networks.

PMID- 15506866
TI  - Toward an understanding of the relationships among organizational change,
      individual differences, and changes in person-environment fit: a cross-level
      study.
AB  - Organizational behavior literature has not typically viewed person-environment (P
      E) fit as an outcome of change. Whereas the study of antecedents to employees'
      fit with their work environment has largely been restricted to the selection and
      socialization of newcomers, this study examines individuals' perceptions of
      changes in P-E fit in relation to organizational changes occurring in 34
      different organizational work units. Results suggest that the relationships
      between organizational change and perceived changes in fit are best understood as
      interactions between the characteristics of the change process, the extent of
      change, and individual differences. Both age and mastery orientation related to
      perceived changes in P-E fit through interactions with aspects of the change
      process.

PMID- 15506867
TI  - Challenge and hindrance stress: relationships with exhaustion, motivation to
      learn, and learning performance.
AB  - In a study of 696 learners, the authors found that stress associated with
      challenges in the learning environment had a positive relationship with learning
      performance and that stress associated with hindrances in the learning
      environment had a negative relationship with learning performance. They also
      found evidence suggesting that these stress-learning performance relationships
      were partially mediated by exhaustion and motivation to lean. Both forms of
      stress were positively related to exhaustion, and exhaustion was negatively
      related to learning performance. Hindrance stress was negatively related to
      motivation to learn, challenge stress was positively related to motivation to
      learn, and motivation to learn was positively related to learning performance.
      Implications with respect to theory and practice are discussed.

PMID- 15506868
TI  - Why does dissimilarity matter? Exploring self-categorization, self-enhancement,
      and uncertainty reduction.
AB  - Although relational demographers have based their arguments on self
      categorization theory, they have paid little attention to the underlying
      processes associated with this theory. The authors examined whether demographic
      dissimilarity affects individuals' identification with groups by affecting the
      group's prototype valence and clarity and the individual's perceptions of self
      prototypicality. The data showed that the proportion of women and non-Australians
      in 34 work groups negatively influenced prototype valence, prototype clarity, and
      self-prototypicality for all members of the group. These results provide support
      for the continued use of self-categorization theory by relational demographers.

PMID- 15506869
TI  - Personality and transformational and transactional leadership: a meta-analysis.
AB  - This study was a meta-analysis of the relationship between personality and
      ratings of transformational and transactional leadership behaviors. Using the 5
      factor model of personality as an organizing framework, the authors accumulated
      384 correlations from 26 independent studies. Personality traits were related to
      3 dimensions of transformational leadership--idealized influence-inspirational
      motivation (charisma), intellectual stimulation, and individualized consideration
      -and 3 dimensions of transactional leadership--contingent reward, management by
      exception-active, and passive leadership. Extraversion was the strongest and most
      consistent correlate of transformational leadership. Although results provided
      some support for the dispositional basis of transformational leadership-
      especially with respect to the charisma dimension--generally, weak associations
      suggested the importance of future research to focus on both narrower personality
      traits and nondispositional determinants of transformational and transactional
      leadership.

PMID- 15506870
TI  - Work flow policy and within-worker and between-workers variability in
      performance.
AB  - Work flow policies are shown to induce a change in average between-workers
      variability (worker heterogeneity) and within-worker variability in performance
      times. In a laboratory experiment, the authors measured the levels of worker
      heterogeneity and within-worker variability under an individual performance
      condition, a work sharing condition, and a fixed assignment condition. The work
      sharing policy increased the levels of worker heterogeneity and worker
      variability, whereas the fixed assignment policy decreased them. These effects,
      along with work flow policy main effects on mean performance times and
      variability are examined. This article represents an initial step in
      understanding effects that may be important in the selection of an operating
      policy, the ignorance of which may lead to costly misestimates of performance.

PMID- 15506871
TI  - An fMRI study of episodic memory: retrieval of object, spatial, and temporal
      information.
AB  - Sixteen participants viewed a videotaped tour of 4 houses that highlighted a
      series of objects and their spatial locations. Participants were tested for
      memory of object, spatial, and temporal-order information while undergoing
      functional magnetic resonance imaging. Preferential activation was observed in
      the right parahippocampal gyrus during the retrieval of spatial-location
      information. Retrieval of contextual information (spatial location and temporal
      order) was associated with activation in the right dorsolateral prefrontal
      cortex. In bilateral posterior parietal regions, greater activation was
      associated with processing of visual scenes regardless of the memory judgment.
      These findings support current theories positing roles for frontal and medial
      temporal regions during episodic retrieval and suggest a specific role for the
      hippocampal complex in the retrieval of spatial-location information.

PMID- 15506872
TI  - A double dissociation between mood states and personality traits in the anterior
      cingulate.
AB  - Neuroticism and extraversion are personality traits associated with negative and
      positive mood states, respectively, confounding trait and state factors that may
      affect brain responses to emotional stimuli. The authors dissociated these
      factors using fMRI and the emotional Stroop attention task: Anterior cingulate
      (AC) response to positive stimuli varied as a function of personality trait, but
      not mood state, whereas AC response to negative stimuli varied as a function of
      mood state, but not personality trait. Negative mood, but not personality trait,
      also increased the functional connectivity between AC and other regions. Variance
      in AC activation can thus be ascribed to an intersubject variable (extraversion)
      when responding to positive stimuli and an intrasubject variable (mood) when
      responding to negative stimuli. The former may explain stable differences between
      extraverts and introverts. The latter may provide an adaptive mechanism to expand
      an individual's dynamic range in response to potentially dangerous or threatening
      stimuli.

PMID- 15506873
TI  - Impact of healthy aging on awareness and fear conditioning.
AB  - Fear conditioning has provided a useful model system for studying associative
      emotional learning, but the impact of healthy aging has gone relatively
      unexplored. The present study investigated fear conditioning across the adult
      life span in humans. A delay discrimination task was employed using visual
      conditioned stimuli and an auditory unconditioned stimulus. Awareness of the
      reinforcement contingencies was assessed in a postexperimental interview.
      Compared with young adult participants, middle-aged and older adults displayed
      reductions in unconditioned responding, discriminant conditioning, and
      contingency awareness. When awareness and overall arousability were taken into
      consideration, there were no residual effects of aging on conditioning. These
      results highlight the importance of considering the influence of declarative
      knowledge when interpreting age-associated changes in discriminative conditioned
      learning.

PMID- 15506874
TI  - Anxious responses to predictable and unpredictable aversive events.
AB  - Anxiety induced by 2 types of predictable and unpredictable aversive stimuli, an
      unpleasant shock or a less aversive airblast to the larynx, were investigated in
      a between-group design. Participants anticipated predictable (signaled) or
      unpredictable (not signaled) aversive events, or no aversive event.
      Unpredictable, relative to predictable, contexts potentiated the startle reflex
      in the shock group but not in the airblast group. These data suggest that
      unpredictability can lead to a sustained level of anxiety only when the pending
      stimulus is sufficiently aversive. Because predictable and unpredictable danger
      may induce different types of aversive responses, the proposed design can serve
      as a useful tool for studying the neurobiology and psychopharmacology of fear and
      anxiety.

PMID- 15506875
TI  - Cortical sensorimotor interactions during the expectancy of a go/no-go task:
      effects of painful stimuli.
AB  - The intent of this electroencephalography study was to investigate the
      competition between cortical nociceptive and cognitive-motor processes preceding
      sensorimotor interactions. Sensorimotor expectancy processes to painful
      stimulation and motor go/no-go demands were indexed over primary sensorimotor and
      midline cortical areas by contingent negative variation (CNV). Before the
      sensorimotor interaction, CNV was observed over midline posterior and bilateral
      central areas. Early expectancy of painful stimulation and the go/no-go task
      induced an evident midline posterior CNV. During the late expectancy period. CNV
      extended to the right central area contralateral to the stimulation. These
      findings suggest a sequential activation of midline posterior and primary
      sensorimotor areas contralateral to the painful stimulation as a reflection of
      the enhanced nociceptive processes preceding painful sensorimotor interactions.

PMID- 15506876
TI  - Breakfasts that release glucose at different speeds interact with previous
      alcohol intake to influence cognition and mood before and after lunch.
AB  - Alcohol consumption and the glycemic load (GL) of a meal interact to influence
      both mood and memory. The authors compared the effects of eating a high GL lunch
      on mood and memory after consumption of a breakfast high in either rapidly (RAG)
      or slowly (SAG) available glucose. When less than 4.5 g of alcohol had been drunk
      the previous evening, the eating of a high RAG meal was associated with better
      memory later in the morning. In contrast, after more than 4.5 g of alcohol had
      been drunk the previous evening, the SAG meal resulted in better memory. After
      lunch, if more than 4.5 g alcohol had been drunk the previous evening, the RAG
      breakfast, but neither the SAG meal nor fasting, resulted in a more confused
      feeling.

PMID- 15506877
TI  - Effects of conditioning during amygdalar inactivation on training-induced
      neuronal plasticity in the medial geniculate nucleus and cingulate cortex in
      rabbits (Oryctolagus cuniculus).
AB  - This study addressed the amygdala's role in avoidance conditioning in rabbits
      (Oryctolagus cuniculus). Intra-amygdalar muscimol infusion before 60 or 120
      conditioning trials blocked training-induced neuronal activity (TIA) in the
      medial geniculate (MG) nucleus. One hundred twenty trials with muscimol blocked
      TIA permanently, during conditioning with muscimol and then later without
      muscimol; 60 trials with muscimol blocked TIA only when muscimol was present.
      Cingulate cortical TIA was blocked only when muscimol was present. Behavioral
      learning did not occur with muscimol, but later learning was facilitated (i.e.,
      savings occurred) in rabbits initially given muscimol plus training. These
      results define the time period wherein amygdalar processes initiate TIA in the MG
      nucleus and suggest that distinct forms of amygdalar processes induce TIA in the
      MG nucleus and cingulate cortex.

PMID- 15506878
TI  - Context memories and reactivation: constraints on the reconsolidation hypothesis.
AB  - Recent evidence suggests that the maintenance of a reactivated contextual-fear
      memory requires a protein-synthesis-dependent reconsolidation process in the
      hippocampus (K. Nader, 2003). In contrast, the authors report a systematic set of
      experiments that failed to find evidence that the rat's reactivated memory for
      context becomes labile and requires a new protein to restabilize. Although
      injecting the protein-synthesis inhibitor into the dorsal hippocampus or
      intracerebroventricularly following the reactivation of the context memory had no
      effect, these same treatments did impair the initial consolidation of the context
      memory and the consolidation of a contextual-fear memory. These results suggest
      that there may be important constraints determining when a reactivated memory
      requires reconsolidation. The authors offer 2 hypotheses about the nature of
      these constraints.

PMID- 15506879
TI  - Pretraining inactivation of the caudal pontine reticular nucleus impairs the
      acquisition of conditioned fear-potentiated startle to an odor, but not a light.
AB  - Recent data from developing rats suggest that structures downstream from the
      amygdala are involved in the acquisition of conditioned fear-potentiated startle
      (FPS). The authors tested this idea in adult rats by temporarily inactivating the
      structure critical for FPS, the caudal pontine reticular nucleus (PnC), during
      fear conditioning. When the conditioned stimulus (CS) was an odor, rats displayed
      freezing, but not FPS, at test. This effect was not due to a decrease in
      footshock sensitivity. Further, no savings were evident on retraining. When the
      CS was a light, inactivation of the PnC had no effect on the acquisition of FPS.
      Thus, the PnC may be crucial for the acquisition of conditioned FPS to an odor,
      but not a light.

PMID- 15506880
TI  - Habituation of the acoustic and the tactile startle responses in mice: two
      independent sensory processes.
AB  - To test whether habituation is specific to the stimulus modality, the authors
      analyzed cross-habituation between the tactile startle response' (TSR) and the
      acoustic startle response (ASR). The acoustic artifacts of airpuffs used to
      elicit the TSR were reduced by using a silencer and were effectively masked by
      background noise of 90-100 dB sound-pressure level. ASR was elicited by 14-kHz
      tones. TSR and ASR habituated in DBA and BALB mice: both the TSR and ASR
      habituated to a greater extent in DBA mice than in BALB mice. In both strains,
      habituation of the TSR did not generalize to the ASR, and vice versa. From this,
      the authors concluded that habituation of startle is located in the sensory
      afferent branches of the pathway.

PMID- 15506881
TI  - Lateralized attentional functions of cortical cholinergic inputs.
AB  - The integrity of the cortical cholinergic input system is necessary for attention
      performance. This experiment tested hypotheses concerning the lateralized
      contributions of cortical cholinergic inputs to attention performance by
      assessing the effects of unilateral lesions of basal forebrain cholinergic
      neurons on sustained attention performance. Loss of right-hemispheric cortical
      cholinergic inputs impaired the rats' ability to detect signals but did not
      affect nonsignal trial performance. Conversely, loss of left-hemispheric cortical
      cholinergic inputs increased the number of false alarms in nonsignal trials.
      These data correspond with hypotheses about the mediation of detection processes
      primarily by right-hemispheric circuits and executive aspects of attention
      performance by left-hemispheric systems. Cortical cholinergic inputs represent a
      major component of the brain's lateralized attention systems.

PMID- 15506882
TI  - Objects and positions in visual scenes: effects of perirhinal and postrhinal
      cortex lesions in the rat.
AB  - The authors assessed rats' encoding of the appearance or egocentric position of
      objects within visual scenes containing 3 objects (Experiment 1) or 1 object
      (Experiment 2A). Experiment 2B assessed encoding of the shape and fill pattern of
      single objects, and encoding of configurations (object + position, shape + fill).
      All were assessed by testing rats' ability to discriminate changes from familiar
      scenes (constant-negative paradigm). Perirhinal cortex lesions impaired encoding
      of objects and their shape; postrhinal cortex lesions impaired encoding of
      egocentric position, but the effect may have been partly due to entorhinal
      involvement. Neither lesioned group was impaired in detecting configural change.
      In Experiment 1, both lesion groups were impaired in detecting small changes in
      relative position of the 3 objects, suggesting that more sensitive tests might
      reveal configural encoding deficits.

PMID- 15506883
TI  - Hippocampal lesions disrupt navigation based on the shape of the environment.
AB  - Geometric information provided by the walls of an environment has a strong
      influence over hippocampal unit activity. This suggests that the hippocampus
      forms part of a cognitive mapping system that encodes geometric relationships
      between environmental cues and the animal's location. Here, the authors show for
      the first time that excitotoxic lesions of the hippocampus disrupt the ability of
      rats to navigate to a goal using shape information provided by a solid-walled
      arena and an array of identical landmarks. These results are consistent with
      cognitive mapping theories of hippocampal function and extend previous research
      by showing that hippocampal cell loss impairs navigation with respect to shape
      information provided by both physical barriers and an array of landmarks.

PMID- 15506884
TI  - Reversible hippocampal inactivation partially dissociates how and where to search
      in the water maze.
AB  - To assess the interaction between spatial and procedural memory systems, the
      authors developed a learning protocol in the water maze using a rising "Atlantis"
      platform that requires rats to learn to swim to a specific location and, once
      there, to learn a "dwelling" response to raise the platform. In this protocol,
      the effects of temporal inactivation of the dorsal hippocampus with the
      AMPA/kainate receptor antagonist LY326325 on different memory phases were
      investigated. Hippocampal inactivation impaired acquisition of the searching
      task, mainly because of disruption of procedural learning. Inactivation also
      impeded consolidation and retrieval of spatial information, while leaving
      expression of dwelling responses intact. These findings challenge the idea of a
      sharp demarcation between spatial and procedural learning with respect to
      hippocampal involvement.

PMID- 15506885
TI  - Medial septal lesions mimic effects of both selective dorsal and ventral
      hippocampal lesions.
AB  - Electrolytic medial septal (MS) lesions, which depleted acetylcholinesterase
      staining in both dorsal and ventral hippocampus, produced a constellation of
      behaviors, combining aspects of both selective dorsal and ventral hippocampal
      lesion effects. MS lesions impaired spatial working memory on the T maze, thus
      resembling the effects of dorsal hippocampal lesions. In addition, MS lesions
      reduced anxiety during successive alleys (a modified form of the elevated plus
      maze), social interaction, and hyponeophagia tests. MS lesions also reduced
      postshock freezing. These effects more closely resemble those of ventral
      hippocampal lesions. Therefore, the effects of electrolytic MS lesions derive
      from the resulting combined deafferentation of dorsal and ventral hippocampal
      regions, suggesting that previously reported effects of cytotoxic dorsal
      hippocampal lesions are unlikely to be due to a demyelination of fibers of
      passage coursing through the septal pole.

PMID- 15506886
TI  - Complementary tasks to measure working memory in distinct prefrontal cortex
      subregions in rats.
AB  - Acquisition of odor-guided or visually-guided delayed win-shift behavior was
      evaluated in rats after lidocaine-induced inactivation within the agranular
      insular area of the prefrontal cortex (PFC) or the prelimbic area of the PFC.
      Additional sites and tasks were used to control for neuroanatomical and
      behavioral specificity of lidocaine inactivation of the agranular insular and
      prelimbic areas. Results showed that acquisition of the odor-guided delayed win
      shift task was dependent on the agranular insular area, whereas acquisition of
      the visually-guided version was dependent on the prelimbic area. This
      dissociation suggests that the stimulus modality used is critical for revealing
      working memory functions of different PFC subregions. The described methods
      provide a complementary means to study working memory in PFC subregions using a
      radial-arm maze.

PMID- 15506887
TI  - Involvement of central amygdalar and bed nucleus of the stria terminalis
      corticotropin-releasing factor in behavioral responses to social defeat.
AB  - The authors investigated whether corticotropin-releasing factor (CRF) within the
      central nucleus of the amygdala (CeA) and bed nucleus of the stria terminalis
      (BNST) is a critical component of the neural circuitry mediating conditioned
      defeat. In this model, hamsters that have experienced social defeat subsequently
      display only submissive-defensive agonistic behavior instead of territorial
      aggression. Conditioned defeat was significantly reduced following infusion of
      the CRF receptor antagonist D-Phe CRF((12-41)) into the BNST but not into the
      CeA. In another experiment, hamsters given unilateral lesions of the CeA and
      infusions of D-Phe CRF((12-41)) into the contralateral BNST displayed
      significantly less submissive behavior than did controls. These data suggest that
      CRF acts within a neural circuit that includes the amygdala and the BNST to
      modulate agonistic behavior following social defeat.

PMID- 15506888
TI  - Fast positive feedback between the adrenocortical stress response and a brain
      mechanism involved in aggressive behavior.
AB  - Aggressive behavior induces an adrenocortical stress response, and sudden
      stressors often precipitate violent behavior. Experiments in rats revealed a
      fast, mutual, positive feedback between the adrenocortical stress response and a
      brain mechanism controlling aggression. Stimulation of the aggressive area in the
      hypothalamus rapidly activated the adrenocortical response, even in the absence
      of an opponent and fighting. Hypothalamic aggression, in turn, was rapidly
      facilitated by a corticosterone injection in rats in which the natural
      adrenocortical stress response was prevented by adrenalectomy. The rapidity of
      both effects points to a fast, mutual, positive feedback of the controlling
      mechanisms within the time frame of a single conflict. Such a mutual facilitation
      may contribute to the precipitation and escalation of violent behavior under
      stressful conditions.

PMID- 15506889
TI  - Modulation of affect after chronic exposure to the anabolic steroid 17alpha
      methyltestosterone in adult mice.
AB  - A battery of behavioral tasks in C57BL/6J mice was used to assess changes in
      affective components of behavior after systemic exposure to the anabolic
      androgenic steroid (AAS) 17alpha-methyltestosterone (7.5 mg/kg). Gonadal weight
      in both sexes was reduced after 16 days of AAS exposure. Changes in discrete
      components of social behaviors were observed. No changes were recorded in the
      elevated plus-maze, the light-dark transition, and defensive behavior tests on
      exposure to 17alpha-methyltestosterone. When compared with controls, AAS-exposed
      females received a greater number of shocks, and AAS-exposed males displayed a
      shorter recovery time to consume water after a negative reinforcer in the
      modified Vogel conflict test. Results show that systemic exposure to a single AAS
      modified social behaviors, whereas minimal effects on anxiety-related behaviors
      were observed according to sex.

PMID- 15506890
TI  - Behavioral sensitization to apomorphine in pigeons (Columba livia): blockade by
      the D1 dopamine antagonist SCH-23390.
AB  - Repeated administration of apomorphine leads to a context-dependent pecking
      response sensitization. Previously sensitized pigeons (Columba livia) challenged
      with saline in the same context show a conditioned response (CR). The authors
      studied the effects of intrastriatal injections of the dopamine (D(1)) antagonist
      SCH-23390 on both the sensitized response and the CR. When coadministered with
      apomorphine, SCH-23390 inhibited the initial response to apomorphine, prevented
      the development of sensitization, and impaired the maintenance of an already
      developed sensitization. However, SCH-23390 had no effect on the retrieval of a
      previously established CR. It is concluded that the activation of D(1) receptors
      in the caudal avian striatum is necessary for the acquisition and maintenance of
      the sensitization, but not for the expression, of the CR.

PMID- 15506891
TI  - Ethanol palatability and consumption by high ethanol-drinking rats: manipulation
      of the opioid system with naltrexone.
AB  - Three experiments examined the effect of acute naltrexone treatment on both taste
      reactivity and consumption of ethanol in high ethanol-preferring rat lines: Alko
      Alcohol-Accepting (AA) rats (Experiments 1 and 2) and Alcohol-Preferring (P) rats
      (Experiment 3). A 3.0 mg/kg naltrexone dose was ineffective at altering ethanol
      palatability for either line, whereas 7.5 mg/kg was effective at reducing
      palatability of 10% ethanol for AA, but not P, rats, as reflected by both a
      decrease in ingestive responding and an increase in aversive responding. The
      effects of naltrexone on ethanol consumption were quite consistent: At both
      dosages, acute naltrexone treatment significantly decreased consumption of 10%
      ethanol. Termination of naltrexone resulted in an immediate increase in ethanol
      consumption to control levels. Results show that ethanol palatability and
      consumption can be dissociated in the rat and that the organization of
      opioidergic mechanisms that mediate ethanol responses may vary between rat lines.

PMID- 15506892
TI  - Serotonin type 3 receptors modulate the aggression-stimulating effects of
      adolescent cocaine exposure in Syrian hamsters (Mesocricetus auratus).
AB  - Repeated cocaine (0.5 mg/kg) exposure throughout adolescence stimulates offensive
      aggression in hamsters. These studies examined whether the cocaine-induced
      aggressive response was regulated by serotonin Type 3 (5-HT(3)) receptor activity
      and correlated with altered 5-HT(3) receptor expression. Cocaine-treated Syrian
      hamsters (Mesocricetus auratus) were tested for aggression after the
      administration of either the 5-HT(3) antagonist 3-tropanylindole-3-carboxylate
      methiodide (tropisetron; 0.01-1.20 mg/kg) or the 5-HT(3) agonist l-(m
      chlorophenyl)-biguanide hydrochloride (mCPBG; 5.0-15.0 mg/kg), alone or in
      combination. Tropisetron alone dose dependently reduced cocaine-induced
      aggression, with a significant reduction at 0.3 mg/kg, whereas mCPBG was
      ineffective. mCPBG administered prior to tropisetron required a higher dose (1.2
      mg/kg) of antagonist to block aggression, indicating a selective 5-HT(3) effect.
      Cocaine-treated hamsters showed altered 5-HT-sub-3 immunoreactivity in several
      brain areas implicated in aggression control. These data support a role for 5
      HT(3) receptors in adolescent cocaine-induced aggression.

PMID- 15506893
TI  - Selective developmental increase in the climbing fiber input to the cerebellar
      interpositus nucleus in rats.
AB  - Previous studies have demonstrated that learning-related cerebellar plasticity
      and stimulus-elicited neuronal activity emerge ontogenetically in parallel with
      delay eyeblink conditioning in rats. The present study examined cerebellar
      interpositus field potentials and multiunit neuronal activity evoked by
      microstimulation of the inferior olive in Postnatal Day 17 and 24 rats. The slope
      and amplitude of the excitatory postsynaptic potential and the number of evoked
      multiunit spikes increased with age, whereas the inhibitory postsynaptic
      potential caused by Purkinje cell input remained stable. These results are
      consistent with the notion that the postsynaptic depolarization of cerebellar
      interpositus neurons caused by cerebellar afferents (e.g., the climbing fibers of
      the inferior olive) is a critical factor contributing to the ontogeny of delay
      eyeblink conditioning in rats.

PMID- 15506894
TI  - Deficits in attentional orienting following damage to the perirhinal or
      postrhinal cortices.
AB  - The authors used an associative learning paradigm to assess the effects of
      perirhinal or postrhinal damage on attentional orienting. Control rats and rats
      with lesions of either the perirhinal or postrhinal cortex initially displayed
      high levels of orienting behavior (rearing) to presentations of a light cue.
      Continued nonreinforced presentations resulted in normal habituation of the
      response. In addition, orienting reemerged in control rats, indicating increased
      attentional processing of the cue. This conditioned orienting did not reemerge in
      rats with either perirhinal or postrhinal lesions, providing direct evidence that
      the rat perirhinal and postrhinal cortices each play a role in attention. These
      results are consistent with an emerging view that some structures within the
      medial temporal lobe have nonmnemonic functions.

PMID- 15506895
TI  - Effects of exercise on Pavlovian fear conditioning.
AB  - Exercise promotes multiple changes in hippocampal morphology and should, as a
      result, alter behavioral function. The present experiment investigated the effect
      of exercise on learning using contextual and auditory Pavlovian fear
      conditioning. Rats remained inactive or voluntarily exercised (VX) for 30 days,
      after which they received auditory-cued fear conditioning. Twenty-four hours
      later, rats were tested for learning of the contextual and auditory conditional
      responses. No differences in freezing behavior to the discrete auditory cue were
      observed during the training or testing sessions. However, VX rats did freeze
      significantly more compared to controls when tested in the training context 24 hr
      after exposure to shock. The enhancement of contextual fear conditioning provides
      further evidence that exercise alters hippocampal function and learning.

PMID- 15506896
TI  - Environmental enrichment facilitates amygdala kindling but reduces kindling
      induced fear in male rats.
AB  - The purpose of this experiment was to determine the effect of prior environmental
      enrichment on the acquisition of kindling and the expression of kindling-induced
      fear. Sixty male rats were housed either in an enriched environment or in
      isolation, starting immediately after weaning. As adults, they were subjected to
      either 50 amygdala-kindling stimulations or sham stimulations, followed by
      testing in an unfamiliar open field. The kindled-enriched rats acquired the
      kindled state more quickly than did the kindled-isolated rats, but they also
      showed less fear in the open field than did the kindled-isolated rats. These
      results suggest that environmental enrichment has differential effects on
      kindling acquisition and its behavioral consequences.

PMID- 15506897
TI  - Exploring the brain's interface between personality, mood, and emotion:
      theoretical comment on Canli et al. (2004).
AB  - T. Canli et al., 2004 use functional MRI to explore the neural interface between
      personality, mood, and emotional responses. Their finding of a double
      dissociation in brain response to emotional stimuli based on personality and mood
      state has significant implications for our understanding of the effects of
      personality traits and mood states on the neural bases of emotion and cognition.

PMID- 15506898
TI  - Fear, conditioning, and aging: theoretical comment on LaBar et al. (2004).
AB  - Age-related impairments in associative learning have been found in studies using
      classical conditioning of motor responses. However, it is as yet unclear whether
      conditioning of fear responses is similarly affected by aging. K. S. La Bar et
      al. (2004) aimed to address this issue by studying age effects on fear
      conditioning applying a discrimination paradigm. Considering these results, this
      commentary discusses methodological issues in investigating fear conditioning as
      well as similarities and differences between associative learning of motor and
      autonomic responses with respect to neuronal substrates, susceptibility to aging,
      and the role of awareness of stimulus contingencies in mediating aging effects.

PMID- 15506899
TI  - Memory reconsolidation hypothesis revived but restrained: theoretical comment on
      Biedenkapp and Rudy (2004).
AB  - J. C. Biedenkapp and J. W. Rudy (2004) reported that the protein synthesis
      inhibitor anisomycin administered into the hippocampus after context preexposure
      or contextual fear conditioning impaired subsequent retention performance. In
      contrast, anisomycin administered after context memory retrieval did not impair
      subsequent contextual fear conditioning. Their findings challenge the hypothesis
      that memory retrieval induces memory reconsolidation and suggest that the
      hypothesis needs to be constrained to account for negative findings. However,
      their evidence does not suggest compelling clues to how the hypothesis might be
      constrained to accommodate the findings. Thus, it is not yet clear whether their
      findings can be explained by a revised reconsolidation hypothesis, or whether
      some other hypothesis is required to account for postretrieval memory impairment,
      when it is observed.

PMID- 15506900
TI  - Aggression upon adolescent cocaine exposure linked to serotonin anomalies:
      theoretical comment on Ricci et al. (2004).
AB  - Aggressive tendencies may be linked to the psychopharmacology of cocaine, yet few
      experimental approaches have been brought to bear on understanding the
      neurobiological implications of cocaine exposure during the developmentally
      sensitive period of adolescence. In this issue, Melloni and coauthors (L. A.
      Ricci, J. M. Grimes, & R. H. Melloni, 2004) present convincing evidence that the
      development of serotonin signal cascades in key brain regions can be disrupted by
      cocaine administration, resulting in an aggressive response in adolescents. These
      findings may allow the development of new therapeutic approaches to tailor
      pharmacotherapy for adolescents experiencing problems with aggressive behavior
      and/or impulse control associated with illicit drug use.

PMID- 15506901
TI  - Compound measure of hand-foot-eye preference masked opposite turning behavior in
      healthy right-handers and non-right-handers: technical comment on Mohr et al.
      (2003).
AB  - A previous article reported opposite turning behavior in right-handers and non
      right-handers (C. Mohr. T. Landis, H. S. Bracha, & P. Brugger, 2003). This
      observation appears contradictory to the 1st study on long-term spontaneous
      turning behavior in healthy participants (H. S. Bracha, D. J. Seitz, J. Otemaa, &
      S. D. Click, 1987). These latter authors found a complex interaction between
      hemispheric dominance, preferred turning side, and sex. C. Mohr et al. (2003)
      argued that the differentiation of the population in hemisphere-dominant groups
      by a compound measure of hand-foot-eye preference might have masked their recent
      finding. Thus, this commentary presents a reanalysis of the original data set (H.
      S. Bracha et al., 1987). Replicating recent observation, right-handers preferred
      left-sided turns; and non-righthanders, right-sided turns. This replication
      strengthens the proposition that handedness and turning behavior might depend on
      interhemispheric dopamine asymmetries.

PMID- 15506902
TI  - Chest pain of esophageal origin.

PMID- 15506903
TI  - Diagnosis of Helicobacter pylori infection using urease rapid test in patients
      with bleeding duodenal ulcer: influence of endoscopic signs and simultaneous
      corporal and antral biopsies.
AB  - INTRODUCTION: The sensitivity of invasive diagnostic methods for Helicobacter
      pylori (H. pylori) infection, particularly of urease rapid test, is decreased in
      cases of gastroduodenal ulcer and upper gastrointestinal bleeding. OBJECTIVES: To
      assess the influence of blood in the stomach or recent bleeding endoscopic signs
      in the diagnostic sensitivity of urease rapid test among patients with bleeding
      duodenal ulcer, as well as the influence of simultaneously collecting corporal
      and antral biopsy samples. PATIENTS AND METHODS: 120 patients, 85 male and 35
      female, with an average age of 62 (18-88) years, who were admitted to our
      Hospital due to bleeding duodenal ulcer and who received an endoscopic diagnosis
      within 24 hours of admission were included. None of the patients had been under
      treatment with non-steroideal antiinflammatory drugs, proton-pump inhibitors or
      antimicrobial drugs in the two weeks prior to the bleeding event, and none had
      received eradicating therapy for H. pylori. In this group of selected patients an
      H. pylori infection rate nearing 100% was assumed. H. pylori infection was ruled
      out using antral biopsy (69 cases) or both antral and fundic biopsies (51 cases)
      for urease rapid testing (Jatrox-H.p.-Test). Patients were classified in three
      groups according to their endoscopic bleeding signs: a) presence of blood in the
      stomach or recent bleeding ulcer (21 cases); b) ulcer showing non-recent bleeding
      signs (38 cases); and c) ulcer without bleeding signs (61 cases). The sensitivity
      of the urease rapid test was compared between patient groups. Similarly, urease
      test results with an antral biopsy sample were compared in 100 patients with non
      bleeding duodenal ulcer. RESULTS: Urease test was positive in 93% of patients
      with non-bleeding duodenal ulcer, and in 83% of patients with upper
      gastrointestinal bleeding, which reached statistical significance (p = 0.019).
      This test was positive in 82.6% of patients with an antral biopsy, and in 82.3%
      of patients with combined antral and fundic biopsies. In group A, urease test was
      positive in 90.5% of patients; in group B, it was positive in 89.5% of patients,
      and in group C, the test turned positive in 75.4% of patients. Statistical
      differences were only reached when patients in group C were compared to patients
      in groups A and B together (p = 0.037). CONCLUSIONS: 1. The presence of either
      blood in the stomach or recent bleeding endoscopic signs appeared not to be the
      conditioning factor for the decreased sensitivity of urease test among patients
      with bleeding duodenal ulcer. 2. The decreased sensitivity of this test in
      patients with upper gastrointestinal bleeding is more evident during the
      resolution stage, and it does not seem to occur because of H. pylori migration
      from the antrum to the corporal gastric region.

PMID- 15506904
TI  - Role of stationary esophageal manometry in clinical practice. Manometric results
      in patients with gastroesophageal reflux, dysphagia or non-cardiac chest pain.
AB  - The present study was carried out to evaluate the diagnostic usefulness of
      stationary esophageal manometry in 263 patients divided into three groups: 150
      patients with reflux symptoms, 68 with dysphagia, and 45 with non-cardiac chest
      pain. Patients with endoscopic abnormalities were excluded. Standard manometry
      was performed following the station pull-through technique. In the group of
      patients with reflux symptoms 40.7% had a normal manometry and 57.3% had
      abnormalities, being the most frequent (43%) hypotensive lower esophageal
      sphincter. In the dysphagia group, 20.6% of manometries were normal and 79.4%
      were abnormal, of which achalasia was the most frequent disorder (53.7%). In the
      case of non-cardiac chest pain, 42.2% of patients had a normal manometry and
      57.8% an abnormal one, of which hypotensive lower esophageal sphincter was the
      most frequent abnormality. A significant higher proportion of manometric
      alterations were found in the dysphagia group compared to reflux symptoms and non
      cardiac chest pain (p < 0.05). No statistical differences were found between the
      reflux and the non-cardiac chest pain groups. Manometry yields a higher
      diagnostic value in patients with dysphagia, and therefore manometry should be
      performed routinely after the exclusion of any organic esophageal disease.
      Manometry is not a first-choice functional diagnostic test in the study of
      patirnts with gastroesophageal reflux or non-cardiac chest pain.

PMID- 15506905
TI  - Diverse clinical presentations of celiac disease in the same family.
AB  - We performed a family study to evaluate a total of 34 extended family members (8
      siblings, 23 children and nephews, and 3 grandchildren) of an adult patient with
      celiac disease (CD), a 58- year-old male with severe neurologic involvement
      manifested as myoclonias. We found 3 other members affected with CD (a 44-year
      old sister, a 39-year old niece, and a 26-year old nephew). Two of them were
      completely asymptomatic and all had hypertransaminasemia. All exhibited a villous
      atrophy pattern of the duodenal mucosa (1 mild, 1 moderate, 1 severe). Overall
      family involvement was 11.8% (4/14). We wish to emphasize the need to perform
      extended family studies when diagnosing a case of CD, since risk is not
      restricted to only first-degree relatives.

PMID- 15506906
TI  - Incidence and factors influencing on Helicobacter pylori infection recurrence.
AB  - OBJECTIVES: a) To determine the rate of H. pylori reinfection after successful
      eradication in a 4-year follow-up study; and b) To evaluate the contribution of
      different factors in the infection relapse. PATIENTS AND METHODS: A total of 208
      patients (age range 18-81 years; average 50 years; 87 women) who had been
      successfully treated for H. pylori infection were included. Annually, urea breath
      test was assessed to determine H. pylori status after eradication. Age, sex,
      rural/urban environment, smoking habit, treatment regimens against H. pylori and
      urea breath test values were evaluated. RESULTS: reinfection occurred in 9,6% of
      patients observed, 6,7% (14/208) in the first year, 1,9% (4/208) in the second
      year, 1% (2/208) in the third and 0% in the forth. Risk factors for infection
      recurrence were younger age and higher values of urea breath test in the
      multivariante analysis. CONCLUSIONS: annual reinfection rate was 2,4 pacients
      year. Younger patients and higher values of urea breath test were factors
      associated with a higher rate of reinfection relapse. Annually, urea breath test
      should be performed to detect reinfection in order to avoid ulcer complications.

PMID- 15506907
TI  - Non-alcoholic statohepatitis: physiopathological, clinical and therapeutic
      implications.

PMID- 15506908
TI  - Chronic pancreatitis: controversies in etiology, diagnosis and treatment.
AB  - The pathogenesis of idiopathic chronic pancreatitis remains poorly understood
      despite the high expectations for ascribing the pancreatic damage in affected
      patients to genetic defects. Mutations in the cationic trypsinogen gene,
      pancreatic secretory trypsin inhibitor, and the cystic fibrosis conductance
      regulator gene do not account for the chronic pancreatitis noted in most patients
      with idiopathic chronic pancreatitis. Small duct chronic pancreatitis can be best
      diagnosed with a hormone stimulation test. Endoscopic ultrasonography can detect
      abnormalities in both the parenchyma and ducts of the pancreas. The true value of
      endoscopic ultrasonography in diagnosing small duct chronic pancreatitis remains
      to be fully defined and is under active investigation. It is not clear whether
      endoscopic ultrasonography is more sensitive for early structural changes in
      patients with small duct disease or is over diagnosing chronic pancreatitis.
      Pancreatic enzyme supplementation with non-enteric formulation along with acid
      suppression (H2 blockers or proton pump inhibitors) is an effective therapy for
      pain in patients with small duct chronic pancreatitis. The role of endoscopic
      ultrasonography-guided celiac plexus block should be limited to treating those
      patients with chronic pancreatitis whose pain has not responded to other
      modalities. Total pancreatectomy followed by autologous islet cell
      autotransplantation appears to be potential therapeutic approach but for now
      should be considered experimental.

PMID- 15506909
TI  - Safe endoscopic resection of gangliocytic paraganglioma of the major duodenal
      papilla.
AB  - A case of gangliocytic paraganglioma of the papilla of Vater in a 76-year-old man
      with a history of recurrent obstructive jaundice is presented. This is the first
      case of gangliocytic paraganglioma of the major papilla successfully resected by
      endoscopic ampullectomy.

PMID- 15506910
TI  - Giant cavernous hemangiomas of the liver.

PMID- 15506911
TI  - [Detection of massive gastrointestinal bleeding with computed tomography but not
      detected with angiography].

PMID- 15506912
TI  - [Hematoma of the rectus abdominis after diagnostic paracentesis in a cirrhotic
      patient].

PMID- 15506916
TI  - Continuous production of monoclonal antibody in a packed-bed bioreactor.
AB  - In the present study the growth and MAb (monoclonal antibody) production of a
      mouse x mouse hybridoma cell producing anti-digoxin MAb was evaluated. The
      hybridoma cells entrapped within the support matrix Fibra-Cel were cultured in
      batch and continuous mode following special protocols. Cell-culture studies were
      performed in a 1-litre spinner basket containing 3 g.litre-1 support matrix.
      Batch culture was operated with the cell density of 42x10(6) cells. During the 7
      days of culture, the medium was sampled daily in order to assess glucose and MAb
      concentrations and the lactate dehydrogenase released into the culture medium.
      After a culture period of 72 h, the cell density and MAb concentration were found
      to be 10.4x10(7) cells/3 g of NWPF (non-woven polyester fibre) discs and 250
      microg/ml respectively. This yield gradually decreased to 0.55x10(6) cells/3 g of
      packaging material and 60 microg/ml respectively at the end of the batch culture.
      In the continuous-culture studies, the batch culture was initially operated for
      64.5 h and then continuous flow was started at the dilution rates of 0.15, 0.2,
      0.25 and 0.3 day-1 and finally stabilized at 0.25 day-1 within 288 h (12 days).
      The MAb concentration at steady state was found to be 116-120 microg/day per ml,
      and the yield of operation was 62.5 mg/day per ml, which was 3.5 times higher
      than that of batch culture. In conclusion, a packed-bed bioreactor with the
      support matrix Fibra-Cel, operated in continuous-feeding mode, is more efficient
      for large-scale MAb production than a batch culture. On the other hand, by using
      a continuous-culture system, a better supply of nutrients and removal of
      inhibitory metabolites and proteolytic enzymes was obtained.

PMID- 15506917
TI  - Is the regulation of galactose 1-phosphate tuned against gene expression noise?
AB  - The average number of mRNA molecules per active gene in yeast can be remarkably
      low. Consequently, the relative number of copies of each transcript per cell can
      vary greatly from moment to moment. When these transcripts are encoding metabolic
      enzymes, how do the resulting variations in enzyme concentrations affect the
      regulation of metabolic intermediates? Using a kinetic model of galactose
      utilization in yeast, we analysed the transmission of noise from transcription
      and translation on metabolic intermediate regulation. In particular, the effect
      of the kinetic properties of the galactose-1-phosphate uridylyltransferase
      reaction on the transmission of noise was analysed.

PMID- 15506918
TI  - The ubiquitous phosphoinositides.
AB  - There are now known to exist seven phosphoinositides all derived through various
      metabolic routes from the parent lipid phosphatidylinositol. With one additional
      metabolite, diacylglycerol, these represent a rich resource of bioactive lipids
      responsible for recruiting protein effectors and marking membrane compartments.
      The metabolic map of this pathway and the nature of the binding partner
      interactions are reviewed.

PMID- 15506919
TI  - Proteomic analysis of chromatin-modifying complexes in Saccharomyces cerevisiae
      identifies novel subunits.
AB  - Epigenetics is the alteration of phenotype without affecting the genotype. An
      underlying molecular mechanism of epigenetics is the changes of chromatin
      structure by covalent histone modifications and nucleosome reorganization. In the
      yeast, Saccharomyces cerevisiae, two of the most well-studied macromolecular
      complexes that perform these epigenetic changes are the ATP-dependent Swi/Snf
      chromatin-remodelling complex and the SAGA histone acetyltransferase complex. To
      understand fully the mechanism by which these large protein complexes perform
      their functions in the cell, it is crucial that all the subunits of these
      complexes are identified. In an attempt to identify new subunits associated with
      SAGA and Swi/Snf, we used tandem affinity purification, followed by a
      multidimensional protein identification technology to analyse the subunit
      composition. Our analysis identified two novel proteins, one associated with
      SAGA, YPL047W (Sgf11), and another associated with Swi/Snf, Rtt102.

PMID- 15506920
TI  - Structure and chemistry of the Sir2 family of NAD+-dependent histone/protein
      deactylases.
AB  - The yeast Sir2 (silent information regulator-2) protein functions as an NAD(+)
      dependent histone deacetylase to silence gene expression from the mating-type
      locus, tolomeres and rDNA and also promotes longevity and genome stability in
      response to calorie restriction. Homologues of yeast Sir2 have been identified in
      the three domains of bacteria, archaea and eukaryotes; in mammalian cells, Sir2
      proteins also deacetylate non-histone proteins such as the p53 tumour suppressor
      protein, alpha-tubulin and forkhead transcription factors to mediate diverse
      biological processes including metabolism, cell motility and cancer. We have
      determined the X-ray crystal structure of a Sir2 homologue from yeast Hst2
      (yHst2), in various liganded forms, including the yHst2/acetyl-Lys-16 histone
      H4/NAD(+) ternary complex; we have also performed related biochemical studies to
      address the conserved mode of catalysis by these enzymes as well as the
      distinguishing features that allow different members of the family to target
      their respective cognate substrates. These studies have implications for the
      structure-based design of Sir2-specific small molecule compounds, which might
      modulate Sir2 function for therapeutic application.

PMID- 15506921
TI  - Zebularine: a new drug for epigenetic therapy.
AB  - Regulatory genes are often hypermethylated at their promoter 5' regions and
      silenced in cancer. Epigenetic therapy with DNA methylation inhibitors have been
      shown to result in the demethylation and reactivation of these genes. Zebularine
      is a recently discovered mechanism-based inhibitor of DNA methylation, and has
      received much attention for its potential in clinical use. Further studies
      exploring the effectiveness of zebularine in a variety of settings could allow
      the development of novel therapies for cancer.

PMID- 15506922
TI  - Control of gene expression by CpG island methylation in normal cells.
AB  - The role of DNA methylation in the control of mammalian gene expression has been
      the subject of intensive research in recent years, partly due to the critical
      role of CpG island methylation in the inactivation of tumour suppressor genes
      during the development of cancer. However, this research has also helped
      elucidate the role that DNA methylation plays in normal cells. At present, it is
      also clear that DNA methylation forms an important part of the normal cell
      regulatory processes that govern gene transcription. Methylation, targeted at CpG
      islands, is an important part of the mechanisms that govern X-chromosome
      inactivation; it is also essential for the maintenance of imprinted genes and, at
      least in some cases, is critical in determining the cell-type-specific expression
      patterns of genes. Study of these examples will be important in identifying the
      mechanisms that control targeting of DNA methylation and how these processes are
      disrupted during disease pathogenesis.

PMID- 15506923
TI  - CpG-island methylation and epigenetic control of resistance to chemotherapy.
AB  - Aberrant methylation of CpG islands (CpG-rich regions of DNA associated with the
      promoters of many genes) is associated with transcriptional inactivation of genes
      involved in tumour development. Genes involved in key DNA damage response
      pathways, such as cell-cycle control, apoptosis signalling and DNA repair can
      frequently become epigenetically silenced and methylated in tumours. This may
      lead to differences in intrinsic sensitivity of tumours to chemotherapy,
      depending on the specific function of the gene inactivated. Furthermore,
      chemotherapy itself may exert a selective pressure on epigenetically silenced
      drug sensitivity genes present in subpopulations of cells, leading to acquired
      chemoresistance. Clinical trials of epigenetic therapies are now in progress, and
      epigenetic profiling using DNA methylation will provide guidance on optimization
      of the use of these therapies with conventional chemotherapy, as well as helping
      to identify patient populations who may particularly benefit from such
      approaches.

PMID- 15506924
TI  - HMGN proteins play roles in DNA repair and gene expression in mammalian cells.
AB  - HMGN (high-mobility-group N) family members are vertebrate proteins that unfold
      chromatin and promote transcription and replication of chromatin templates in
      vitro. However, their precise roles in vivo have been elusive until recently.
      This paper summarizes recent advances from studies of Hmgn1 knockout mice and
      genetically engineered cell lines that are beginning to reveal the diverse roles
      that HMGN proteins play in DNA repair and transcription within mammalian cells.

PMID- 15506925
TI  - Complex regulation and nuclear localization of JRK protein.
AB  - The mouse jerky gene and its human orthologue, JRK/JH8, encode a putative DNA
      binding protein with homology to the CENP-B (centromere-binding protein B).
      Disruption of the mouse jerky gene by transgene insertion causes generalized
      recurrent seizures reminiscent of human idiopathic generalized epilepsy. In
      addition (and similar to a cenp-b null mouse) jerky null mice exhibit postnatal
      weight loss and reduced fertility. Using fluorescence confocal microscopy, the
      cellular localization of a JRK-GFP fusion (where GFP stands for green fluorescent
      protein) was investigated in HeLa cells. JRK-GFP has a dynamic expression pattern
      in the interphase nucleus, localizing in a small number of punctate nuclear foci
      and in the nucleolus. The JRK-GFP foci number changes during the cell cycle, but
      a distinct pattern of three JRK-GFP foci is observed at G(2). The endogenous
      protein behaves in a similar manner to the GFP-fusion protein. JRK-GFP was found
      to co-localize with CREST antigens (which recognize the centromere-binding
      proteins, CENP-A, -B and -C) through S and G(2) phases of interphase and co
      localized completely with a subset of PML nuclear bodies at G(2). We speculate
      that JRK protein associates with a specific chromosomal centromeric locus in
      G(2), where it associates fully with PML bodies. Research is underway to identify
      this locus.

PMID- 15506926
TI  - A molecular code for splicing silencing: configurations of guanosine-rich motifs.
AB  - Alternative pre-mRNA splicing is frequently used to expand the protein-coding
      capacity of genomes, and to regulate gene expression at the post-transcriptional
      level. It is a significant challenge to decipher the molecular language of tissue
      specific splicing because the inherent flexibility of these mechanisms is
      specified by numerous short sequence motifs distributed in introns and exons. In
      the present study, we employ the glutamate NMDA (N-methyl-D-aspartate) R1
      receptor (GRIN1) transcript as a model system to identify the molecular
      determinants for a brain region-specific exon silencing mechanism. We identify a
      set of guanosine-rich motifs that function co-operatively to regulate the CI
      cassette exon in a manner consistent with its in vivo splicing pattern. Whereas
      hnRNP (heterogeneous nuclear ribonucleoprotein) A1 mediates silencing of the CI
      cassette exon in conjunction with the guanosine-rich motifs, hnRNP H functions as
      an antagonist to silencing. Genome-wide analysis shows that, while this motif
      pattern is rarely present in human and mouse exons, those exons for which the
      pattern is conserved are generally found to be skipped exons. The identification
      of a similar arrangement of guanosine-rich motifs in transcripts of the hnRNP H
      family of splicing factors has implications for their co-ordinate regulation at
      the level of splicing.

PMID- 15506927
TI  - Roles of the U5 snRNP in spliceosome dynamics and catalysis.
AB  - Most protein-coding genes in eukaryotes are interrupted by non-coding intervening
      sequences (introns), which must be precisely removed from primary gene
      transcripts (pre-mRNAs) before translation of the message into protein. Intron
      removal by pre-mRNA splicing occurs in the nucleus and is catalysed by complex
      ribonucleoprotein machines called spliceosomes. These molecular machines consist
      of several small nuclear RNA molecules and their associated proteins [together
      termed snRNP (small nuclear ribonucleoprotein) particles], plus multiple
      accessory factors. Of particular interest are the U2, U5 and U6 snRNPs, which
      play crucial roles in the catalytic steps of splicing. In the present review, we
      summarize our current understanding of the role played by the protein components
      of the U5 snRNP in pre-mRNA splicing, which include some of the largest and most
      highly conserved nuclear proteins.

PMID- 15506928
TI  - Transcriptional regulation by the Wilms' tumour suppressor protein WT1.
AB  - Wilms' tumour is a paediatric malignancy of the kidneys and is the most common
      solid tumour found in children. The Wilms' tumour suppressor protein WT1 is
      mutated in approximately 15% of Wilms' tumours, and is aberrantly expressed in
      many others. WT1 can manifest both tumour suppressor and oncogenic activities,
      but the reasons for this are not yet clear. The Wilms' tumour suppressor protein
      WT1 is a transcriptional activator, the function of which is under cell-context
      specific control. We have previously described a small region at the N-terminus
      of WT1 (suppression domain) that inhibits the transcriptional activation domain
      by contacting a co-suppressor protein. We recently identified BASP1 as one of the
      components of the co-suppressor. Here, we analyse the mechanism of action of the
      WT1 suppression domain, and discuss its function in the context of the role of
      WT1 as a regulator of development.

PMID- 15506929
TI  - Regulation of NF-kappaB by atypical activators and tumour suppressors.
AB  - The RelA(p65) NF-kappaB (nuclear factor kappaB) subunit is typically thought of
      as being antiapoptotic and tumour-promoting. However, in our laboratory, we have
      discovered that RelA can inhibit, rather than induce, antiapoptotic gene
      expression when activated by certain chemotherapeutic drugs, UV light or through
      the action of the ARF tumour suppressor. These observations explain why RelA can
      sometimes facilitate rather than inhibit apoptosis and also exhibits tumour
      suppressor characteristics in vivo. A better understanding of these processes and
      an ability to analyse RelA function in tumours could lead to improved cancer
      diagnosis, choice of therapy and, ultimately, development of new drugs.

PMID- 15506930
TI  - The flightless I protein and the gelsolin family in nuclear hormone receptor
      mediated signalling.
AB  - The Drosophila melanogaster flightless I protein and its homologues in higher
      eukaryotes (FliI) are conserved members of the gelsolin family of actin-binding
      proteins. Members of the gelsolin family generally contain three or six copies of
      a 125-amino-acid residue gelsolin-related repeating unit, and may contain
      additional domains including the C-terminal villin-related 'headpiece' or N
      terminal extensions such as the leucine-rich repeat of the FliI protein. Numerous
      studies including work done with mouse knockouts for gelsolin, villin and CapG
      support a role for the family in cytoskeletal actin dynamics. In both fruitfly
      and mouse, the FliI protein is also essential for early development. Recent
      studies indicate that supervillin, gelsolin and FliI are involved in
      intracellular signalling via nuclear hormone receptors including the androgen,
      oestrogen and thyroid hormone receptors. This unexpected role in signalling has
      opened a new area in research on the gelsolin family and is providing important
      new insights into the mechanisms of gene regulation via nuclear receptors.

PMID- 15506931
TI  - Factor inhibiting hypoxia-inducible factor (FIH) and other asparaginyl
      hydroxylases.
AB  - FIH (Factor inhibiting hypoxia-inducible factor), an asparaginyl beta-hydroxylase
      belonging to the super-family of 2-oxoglutarate and Fe(II)-dependent
      dioxygenases, catalyses hydroxylation of Asn-803 of hypoxia-inducible factor, a
      transcription factor that regulates the mammalian hypoxic response. Only one
      other asparaginyl beta-hydroxylase, which catalyses hydroxylation of both
      aspartyl and asparaginyl residues in EGF (epidermal growth factor)-like domains,
      has been characterized. In the light of recent crystal structures of FIH, we
      compare FIH with the EGFH (EGF beta-hydroxylase) and putative
      asparagine/asparaginyl hydroxylases. Sequence analyses imply that EGFH does not
      contain the HXD/E iron-binding motif characteristic of most of the 2-oxoglutarate
      oxygenases.

PMID- 15506932
TI  - Silence is green.
AB  - Small RNAs serve as the specificity determinant for a collection of regulatory
      mechanisms known as RNA silencing. Plants use these mechanisms to control the
      expression of endogenous genes and to suppress unwanted foreign nucleic acids.
      Several gene families implicated in silencing have undergone expansion and
      evidence exists for multiple RNA silencing pathways. Recent progress in defining
      the components of a number of these pathways is examined here.

PMID- 15506933
TI  - RNA interference and double-stranded-RNA-activated pathways.
AB  - RNAi (RNA interference) has become a powerful tool to determine gene function.
      Different methods of expressing the short ds (double-stranded) RNA intermediates
      required for interference in mammalian systems have been developed, including the
      introduction of si (short interfering) RNAs by direct transfection or driven from
      transfected plasmids or lentiviral vectors encoding sh (short hairpin) RNAs.
      Although RNAi relies upon a high degree of specificity, recent findings suggest
      that off-target non-specific effects can be encountered. We found that
      transfection of siRNAs can results in an interferon-mediated activation of the
      JAK/STAT (Janus kinase/signal transducer and activator of transcription) pathway
      and global up-regulation of interferon-stimulated genes. This effect is mediated
      in part by the dsRNA-dependent protein kinase PKR, as this kinase is activated by
      the 21 bp siRNA, and is required in response to the siRNAs. However, the
      transcription factor IRF3 (interferon-regulatory factor 3) is also activated by
      siRNA as a primary response, resulting in the stimulation of genes independent of
      an interferon response. In cells deficient in IRF3, this response is blunted, but
      can be restored by re-introduction of IRF3. Thus siRNAs induce complex signalling
      responses in target cells, leading to effects beyond the selective silencing of
      specific genes.

PMID- 15506934
TI  - Understanding the roles of RecQ helicases in the maintenance of genome integrity
      and suppression of tumorigenesis.
AB  - RecQ helicases are evolutionarily conserved enzymes required for the maintenance
      of genome stability. Mutations in three of the five known human RecQ helicase
      genes cause distinct clinical disorders that are characterized by genome
      instability and cancer predisposition. Recent studies have begun to reveal the
      cellular roles of RecQ helicases and how these enzymes may prevent tumorigenesis
      at the molecular level.

PMID- 15506935
TI  - Poly(ADP-ribose) polymerase inhibitors as potential chemotherapeutic agents.
AB  - PARP [poly(ADP-ribose) polymerase] activity is up-regulated by binding to DNA
      strand breaks and its association with DNA repair is well documented. Many
      anticancer therapies work by inducing breaks in DNA, if unrepaired these can lead
      to cell death. As PARP promotes DNA repair there is a strong rational to suggest
      that its inhibition may increase the efficiency of certain cytotoxic treatments.
      This review discusses the advances made in PARP inhibitor design and the
      mechanism by which they enhance anti-tumour therapies.

PMID- 15506936
TI  - Monitoring base excision repair proteins on damaged DNA using human cell
      extracts.
AB  - BER (base excision repair) is a major pathway for the removal of simple lesions
      in DNA including base damage and base loss (abasic site). We have developed an
      assay, using formaldehyde cross-linking during repair in human cell extracts, to
      observe BER proteins involved in the repair of damaged DNA. This approach allows
      visualization of repair proteins on damaged DNA during BER in human cell extracts
      and provides a detailed view of the molecular events leading to repair.

PMID- 15506937
TI  - Arabidopsis DNA double-strand break repair pathways.
AB  - DSBs (double-strand breaks) are one of the most serious forms of DNA damage that
      can occur in a cell's genome. DNA replication in cells containing DSBs, or
      following incorrect repair, may result in the loss of large amounts of genetic
      material, aneuploid daughter cells and cell death. There are two major pathways
      for DSB repair: HR (homologous recombination) uses an intact copy of the damaged
      region as a template for repair, whereas NHEJ (non-homologous end-joining)
      rejoins DNA ends independently of DNA sequence. In most plants, NHEJ is the
      predominant DSB repair pathway. Previously, the Arabidopsis NHEJ mutant atku80
      was isolated and found to display hypersensitivity to bleomycin, a drug that
      causes DSBs in DNA. In the present study, the transcript profiles of wild-type
      and atku80 mutant plants grown in the presence and absence of bleomycin are
      determined by microarray analysis. Several genes displayed very strong
      transcriptional induction specifically in response to DNA damage, including the
      characterized DSB repair genes AtRAD51 and AtBRCA1. These results identify novel
      candidate genes that encode components of the DSB repair pathways active in NHEJ
      mutant plants.

PMID- 15506938
TI  - Cell cycle-regulated transcription in fission yeast.
AB  - A fundamental process in biology is the mechanism by which cells duplicate and
      divide to produce two identical daughter cells. The fission yeast,
      Schizosaccharomyces pombe, has proved to be an excellent model organism to study
      the role that gene expression plays in this process. The basic paradigm emerging
      is that a number of groups of genes are expressed in successive waves at
      different cell cycle times. Transcription of a particular group is controlled by
      a common DNA motif present in each gene's promoter, bound by a transcription
      factor complex. Each motif and transcription factor complex is specific to the
      time in the cell cycle when the group of genes is expressed. Examples of this are
      the MBF (MCB-binding factor)/MCB (MluI cell cycle box) system controlling gene
      expression at the start of S-phase, and PBF (PCB-binding factor)/PCB (Pombe cell
      cycle box) regulation of transcription at the end of mitosis. In some cases,
      these transcription control systems also operate during the alternative form of
      cell division, meiosis.

PMID- 15506939
TI  - Dissection of the signalling mechanisms underlying FcgammaRIIB-mediated apoptosis
      of mature B-cells.
AB  - The low-affinity receptor for IgG, FcgammaRIIB, negatively regulates BCR (B-cell
      antigen receptor)-mediated proliferative signalling and thus plays an important
      role in feedback inhibition of the humoral immune response. Whereas crosslinking
      of BCR on mature B-cells results in proliferation, co-ligation of FcgammaRIIB
      results in growth arrest and apoptosis. We have now investigated the signals
      underlying FcgammaRIIB-driven apoptosis and found this to be dependent on
      disruption of mitochondrial potential (Deltapsi), involve the pro-apoptotic Bcl-2
      family members, Bid and Bad, and be caspase-independent.

PMID- 15506940
TI  - Mitogenic stimulation of transcription by RNA polymerase III.
AB  - Regulation of protein synthesis is an important aspect of growth control. RNA
      polymerase (pol) III plays a key role in this process by catalysing production of
      tRNA and 5 S rRNA. Growth factors trigger a rapid increase in pol III activity
      and this is essential for cell proliferation. The transcription factor TFIIIB
      plays a key role in controlling pol III activity and is a target for regulation
      by a number of mechanisms. This review will focus on how TFIIIB is targeted by
      these proteins in response to mitogen stimulation.

PMID- 15506941
TI  - Oxidative stress in colon tissue induced by vitamin E depletion.
AB  - Inflammatory disorders of the bowel and colon cancer are associated with elevated
      indices of oxidative stress. Analogous elevations in markers of oxidative stress
      and loss of cell-membrane integrity are also observed in the colons of rats
      deficient in vitamin E (D-alpha-tocopherol), the major lipid-soluble antioxidant
      in biological systems. The causal relationship between colon pathologies
      associated with oxidative stress and dietary deficiency in antioxidant vitamins
      such as vitamin E is still uncertain. Investigation of potential mechanisms by
      which lack of dietary vitamin E may lead to clinically relevant pathological
      changes in colon tissue was conducted using gene expression profiling strategies
      on vitamin E-sufficient and -deficient rats. Morphological changes and increased
      indices of lipid peroxidation were linked to vitamin E deficiency. These changes
      in colon tissue are potentially important in disease pathogenesis of the colon
      linked with oxidative stress or other direct consequences of inadequate levels of
      vitamin E.

PMID- 15506942
TI  - Vitamin A regulates proliferation and apoptosis of human T- and B-cells.
AB  - Vitamin A is known to protect against infections, but it is not established how
      vitamin A metabolites stimulate the immune system. We have investigated the
      effects of physiological levels of retinoic acid on the function of normal human
      T- and B-cells. Surprisingly, we found that the proliferation of B-cells was
      inhibited by retinoids, and that this was due to rapid inhibition of the cell
      cycle machinery regulating G(1)-to-S transition. In contrast, the proliferation
      of T-cells was enhanced by physiological levels of retinoic acid, and the effect
      was due to induction of IL-2 (interleukin 2). The 'non-death-receptor'-mediated
      apoptosis of normal T-cells induced by prolonged (but single) stimulation of the
      cells was also prevented by retinoid acid, and also this effect was mediated via
      enhanced production of IL-2. The induction of IL-2 was at the transcriptional
      level, and all the effects of vitamin A on both B-and T-cells were mediated via
      the nuclear retinoic acid receptors (RARs), and not retinoid X receptors (RXRs).

PMID- 15506943
TI  - Dietary carotenoids, connexins and cancer: what is the connection?
AB  - Carotenoids and retinoids are chemically related; indeed a major source of
      vitamin A in humans occurs through enzymic cleavage of beta-carotene. However,
      most dietary carotenoids cannot be converted into retinoids. Retinoids have
      demonstrated cancer-preventive activities in humans and experimental models;
      however, their toxicity has precluded wide-scale clinical use. In contrast,
      carotenoids are essentially non-toxic and their cancer-preventive activities,
      although strongly supported by epidemiological studies, have only been
      satisfactorily demonstrated in experimental systems. We have shown that in an
      experimental cell culture system consisting of carcinogen-treated 10T1/2 cells,
      both retinoids and all dietary carotenoids examined can reversibly inhibit
      neoplastic transformation in the post-initiation phase of carcinogenesis. This
      activity strongly correlates with their ability to increase gap junctional
      intercellular communication by up-regulating the expression of the gene CX43
      (connexin43). Connexins comprise the structural unit of gap junctions, organelles
      which allow direct transfer of signals, nutrients and waste products between
      contacting cells. CX43 is the most widely expressed member of the gap junction
      family of genes, and we have demonstrated that its expression is strongly down
      regulated in human cancers and in several premalignant conditions. When several
      human tumour cell lines were genetically engineered to conditionally express CX43
      under the influence of a tetracycline promoter, their neoplastic phenotype was
      strongly attenuated. Specifically, induced cells were inhibited from growing in
      an anchorage-independent manner and, additionally, growth as xenografts in
      immunocompromised animals was also strongly attenuated. Growth inhibition in
      suspension was associated both with increased G(1) cell-cycle arrest and with
      increased apoptosis. We propose a model whereby junctional communication allows
      the transfer of growth inhibitory signals from normal to neoplastic cells and
      that retinoids and carotenoids, by increasing signal transfer, act to prevent
      cancer.

PMID- 15506944
TI  - 3'-Untranslated regions are important in mRNA localization and translation:
      lessons from selenium and metallothionein.
AB  - There is increasing evidence that 3'-UTRs (3'-untranslated regions) of mRNAs
      contain regulatory elements that have important roles in post-transcriptional
      control of gene expression. For example, 3'-UTRs are important in determining
      mRNA localization and directing selenocysteine insertion during selenoprotein
      synthesis. Metallothionein mRNA is localized around the nucleus and associated
      with the cytoskeleton; this is determined by the 3'-UTR. Deletion and mutagenesis
      studies are defining the nature of the signal. Incorrect mRNA localization
      prevents subsequent nuclear localization of metallothionein protein and affects
      its function. Selenium (Se) is incorporated as selenocysteine into approx. 30
      mammalian proteins by a mechanism that requires a specific structure within the
      3'-UTR of the corresponding mRNAs. When Se supply is low the effect on
      selenoprotein expression is not uniform but shows differential effects that are
      tissue- and protein-specific; there is a 'prioritization' of selenoprotein
      synthesis that is partly influenced by the 3'-UTRs of the different mRNAs. Single
      nucleotide polymorphisms in the gene regions corresponding to 3'-UTRs could
      potentially influence gene regulation. We have discovered a common polymorphism
      in a part of the glutathione peroxidase 4 gene which corresponds to the 3'-UTR,
      and our recent results suggest that this single-nucleotide polymorphism has
      functional and physiological effects, as well as altered frequency in disease.

PMID- 15506945
TI  - Triacylglycerol-rich lipoprotein-gene interactions in endothelial cells.
AB  - Lipoproteins such as LDL (low-density lipoprotein) and oxidized LDL have
      potentially adverse effects on endothelial cells due to their ability to activate
      pro-inflammatory pathways regulated via the transcription factor NF-kappaB
      (nuclear factor kappaB). Triacylglycerol-rich lipoproteins (the chylomicrons,
      very-low-density lipoprotein and their respective remnant particles) have also
      been implicated in the induction of a pro-inflammatory phenotype and up
      regulation of adhesion molecule expression. Although early studies supported the
      proposal that LPL (lipoprotein lipase)-mediated hydrolysis of TRLs (triglyceride
      rich lipoproteins) at the endothelium could activate the NFkappaB pathway, more
      recent studies provide evidence of pro- and anti-inflammatory responses when
      cells are exposed to fatty acids or TRL particles. A large number of genes are up
      and down-regulated when cells are exposed to TRL, with the net effect reflecting
      receptor- and nonreceptor-mediated pathways that are activated or inhibited
      depending on fatty acid type, the lipid and apolipoprotein composition of the TRL
      and the presence or absence of LPL. Early concepts of TRL particles as
      essentially pro-inflammatory stimuli to the endothelium provide an overly
      simplistic view of their impact on the vascular compartment.

PMID- 15506946
TI  - Dietary lipids and gene expression.
AB  - Nutrition is a key environmental factor that is particularly involved in the
      pathogenesis and progression of several polygenic, diet-related diseases.
      Nutrigenomics refers to the interaction between nutrition and the human genome.
      Dietary fatty acids interact with multiple nutrient-sensitive transcription
      factors. This explains the molecular basis of some of the health effects
      associated with altered dietary fatty acid composition. The metabolic syndrome is
      a very common condition, characterized by insulin resistance, abdominal obesity,
      dyslipidaemia and hypertension. It often precedes Type 2 diabetes mellitus, and
      is associated with a greater risk of cardiovascular disease. Several lines of
      evidence suggest that the interaction between nutrient-derived metabolic
      stressors and pro-inflammatory signals play an important role in the aetiology of
      insulin resistance and the development of the metabolic syndrome. This paper will
      address the interaction between several nutrient-sensitive transcription factors,
      including SREBP (sterol-regulatory-element-binding protein) and NFkappaB (nuclear
      factor kappaB), demonstrating how this interaction may be altered with dietary
      fatty acid interventions.

PMID- 15506947
TI  - Haem oxygenase-1: a target for dietary antioxidants.
AB  - HO-1 (haem oxygenase-1) is a stress-response enzyme involved in the catabolism of
      haem. In animal models, it plays a key protective role in vascular disease. HO-1
      has anti-inflammatory effects in macrophages and is induced by a range of
      stimuli, including antioxidants, in various cell types. As dietary antioxidants
      are considered to be beneficial in vascular disease, their protective effects may
      occur through induction of HO-1. Emerging evidence suggests that a range of
      dietary and other naturally occurring antioxidants stimulate HO-1 expression in
      various cell types, although regulation by these compounds has not been
      investigated in detail. These studies suggest that HO-1 may be a target for
      dietary therapy in vascular disease.

PMID- 15506948
TI  - Folate and DNA methylation during in utero development and aging.
AB  - DNA methylation is one of several epigenetic mechanisms that play a regulatory
      role in genome programming and imprinting during embryogenesis. Aberrant DNA
      methylation has been implicated in the pathogenesis of a number of diseases
      associated with aging, including cancer and cardiovascular and neurological
      diseases. Evidence is accumulating that dietary factors in utero modulate disease
      risk in later life. Although folic acid is a key component of DNA methylation,
      the impact of folic acid availability in utero on DNA methylation patterns and
      disease risk in adulthood is at present poorly characterized. This review
      describes the relationship between folic acid and DNA methylation, and the
      association between DNA methylation during in utero development and aging.

PMID- 15506949
TI  - Oxidant regulation of the bivalent cation transporter Nramp1.
AB  - Nramp1 (murine natural resistance-associated macrophage protein 1 gene)/Slc11a1
      (solute carrier family 11 member a1 gene) encodes a bivalent-metal/iron
      transporter that is expressed within late endosomes/lysosomes of macrophages. A
      functionally null Nramp1 allele that exhibits impaired bivalent cation transport
      enables excessive growth of intracellular pathogens. Iron is important for many
      cellular activities, including defence against pathogens; however, redox
      active/free iron can participate in Fenton chemistry that generates reactive
      oxygen species. Using Raw264.7 cells, non-functional for Nramp1, and stable
      Nramp1 transfectants, we have examined the effects of impaired bivalent cation
      transport on macrophage function using glutathione depletion as OS (oxidant
      stress). Our results demonstrate that OS itself is a signal for increasing Nramp1
      transcription and that Nramp1 expression protects against OS. We suggest that OS
      mediated protection by Nramp1 function may arise from direct removal of redox
      active bivalent cations from a cytosolic pool. We show that OS transcriptional
      responses are probably mediated by the Sp1 transcription factor.

PMID- 15506950
TI  - Investigating mitochondrial radical production using targeted probes.
AB  - A range of mitochondria-targeted probe molecules that comprise a lipophilic
      cation covalently attached to an active moiety have been developed. The
      lipophilic cation causes the accumulation of these molecules into mitochondria,
      driven by the mitochondrial membrane potential. To date, we have targeted
      antioxidants, spin traps, thiol reagents and DNA-alkylating compounds to
      mitochondria. The selective mitochondrial localization of these compounds enables
      us to investigate several aspects of the production of reactive oxygen species by
      mitochondria.

PMID- 15506951
TI  - Reactive sulphur species in oxidative signal transduction.
AB  - Intense interest has been generated by the discovery that reactive oxygen species
      can function as intracellular second messengers. Reactive oxygen species have
      been implicated in diverse cellular processes, including growth factor signal
      transduction, gene expression and apoptosis. Additionally, there is evidence for
      proteins that are regulated by redox environment through the reversible oxidation
      of their cysteine residues. However, the direct reaction of reactive oxygen
      species with cysteine at physiological concentrations is generally a slow
      process, suggesting that intermediates are required to convey efficiently the
      oxidative stimulus. Here, we discuss the evidence that DSOs (disulphide-S-oxides)
      are formed from glutathione under oxidizing conditions and specifically modulate
      the redox status of thiols, indicating the existence of specialized cellular
      oxidative pathways. DSO inactivated glyceraldehyde 3-phosphate and alcohol
      dehydrogenases and released zinc from metallothionein and a zinc finger domain.
      In contrast, equivalent concentrations of H(2)O(2) showed minimal effect. The
      antioxidants ascorbate, NADH, trolox and melatonin were unable to quench DSO
      induced oxidation. These findings support the paradigm of oxidative signal
      transduction and provide a general pathway whereby reactive oxygen species can
      convert thiols into disulphides.

PMID- 15506952
TI  - Redox regulation of phosphatase function.
AB  - Although reactive oxygen species play important roles in cellular physiology as
      signalling molecules, their molecular targets are largely unknown. A probable
      group of targets for mediating many of the effects of reactive oxygen species on
      cell signalling is the large diverse family of cysteine-dependent phosphatases,
      which includes the protein tyrosine phosphatases. Our work and that of others
      suggest that the oxidative inactivation of protein and lipid phosphatases plays
      an important part in signalling, downstream of many cellular stimuli. Future
      studies should give us a clearer picture of the role of phosphatase inactivation
      in cellular behaviour and explain how specificity is achieved in redox
      signalling.

PMID- 15506953
TI  - Genes controlling the metabolic switch in hibernating mammals.
AB  - Hibernating mammals have the ability to decrease their metabolic rate and survive
      up to 6 months without food in an inactive state where body temperatures approach
      0 degrees C. In hibernating 13-lined ground squirrels (Spermophilus
      tridecemlineatus), oxygen consumption holds at 1/30 to 1/50 of the aroused
      condition and heart rates are as low as 3-10 beats/min, compared with 200-300
      beats/min when the animal is active. This seasonal adaptation requires a
      metabolic shift away from the oxidation of carbohydrates and towards the
      combustion of stored fatty acids as the primary source of energy. A key element
      in this fuel switch is the differential expression of the gene encoding pyruvate
      dehydrogenase kinase isoenzyme 4. Pyruvate dehydrogenase kinase isoenzyme 4
      inhibits pyruvate dehydrogenase and thus minimizes carbohydrate oxidation by
      preventing the flow of glycolytic products into the tricarboxylic acid cycle.
      Hibernators also exploit the low-temperature activity of PTL (pancreatic
      triacylglycerol lipase) in both heart and white adipose tissue. Lipolytic
      activity at body temperatures associated with hibernation was examined using
      recombinant ground squirrel and human PTL expressed in yeast. Enzymes from both
      humans and ground squirrel displayed high activity at temperatures as low as 0
      degrees C and showed Q(10) = 1.2-1.5 over the temperature range 37-7 degrees C.
      These studies indicate that low-temperature lipolysis is a general property of
      PTL and does not require protein modifications unique to mammalian cells and/or
      the hibernating state.

PMID- 15506954
TI  - Oligomeric assembly of dopamine D1 and glutamate NMDA receptors: molecular
      mechanisms and functional implications.
AB  - In the striatum, dopamine D(1)R (D(1) receptor) activation potentiates NMDA (N
      methyl-D-aspartate) transmission and is required for NMDA-mediated long-term
      potentiation at corticostriatal synapses. By using a combination of co
      immunoprecipitation, pull-out with glutathione S-transferase-fusion proteins and
      bioluminescence resonance energy transfer, we have reported that the D(1)R forms
      a heteromeric complex with the NMDAR (NMDA receptor) and that this mechanism is
      crucial to recruit the D(1)R to the postsynaptic density. By using confocal and
      radioligand-binding assay, we also demonstrated that the interaction with NMDAR
      abolishes agonist-mediated D(1)R sequestration, indicating that oligomerization
      with NMDAR could represent a novel regulatory mechanism modulating D(1)R cellular
      trafficking and desensitization.

PMID- 15506955
TI  - Kinetics of G-protein-coupled receptor signalling and desensitization.
AB  - The kinetics of G-protein-coupled receptor activation and deactivation has, so
      far, been measured only indirectly, most frequently by assessing the production
      of various second messengers. We have developed methods based on fluorescence
      resonance energy transfer to quantify the kinetics of receptor activation by
      agonist (measured as conformational change in the receptor), the kinetics of G
      protein activation (measured as G-protein subunit rearrangement) and the kinetics
      of receptor inactivation by arrestins (measured as receptor-arrestin
      interaction). Using these methods, we show that receptor activation by agonists
      and signalling to G-proteins occur on the subsecond time scale, whereas receptor
      desensitization is limited by receptor phosphorylation and proceeds more slowly.

PMID- 15506956
TI  - Direct interactions between NMDA and D1 receptors: a tale of tails.
AB  - Considerable evidence has accumulated describing a complex interaction between
      the dopaminergic and glutamatergic pathways. Efforts to describe the mechanisms
      underlying this complex interaction have implicated a functional interaction
      between dopamine and glutamate receptors. Classically, the interaction between
      D(1) and NMDA (N-methyl-D-aspartate) receptors has been proposed to involve the
      activation of second-messenger signalling cascades after receptor stimulation.
      However, in recent years, another paradigm has emerged which involves the direct
      interaction between D(1) and NMDA receptors. The physical association between
      D(1) and NMDA receptors is unique in that two different regions of the D(1) C
      terminus are able to couple specifically and physically with two different NMDA
      subunits. The selective modulation of multiple NMDA receptor-mediated functions
      by direct interactions with D(1) receptors may form a new avenue to identify
      specific targets for therapeutics to modulate NMDA receptor-governed synaptic
      plasticity, neuronal development and disease states.

PMID- 15506957
TI  - Evidence to support a spectrum of active states for the glucagon receptor.
AB  - The ternary complex model suggests that G-protein-coupled receptors resonate
      between inactive (R) and active (R*) forms. Physiologically, R sites ordinarily
      predominate with a few R* sites giving rise to basal activity. Agonists
      recognize, stabilize and increase the R* population, thus altering intracellular
      activity. There is evidence to suggest the possibility of a spectrum of
      conformations between R and R*. Our aim is to study the consequences of putative
      GR (glucagon receptor)-activating mutations using glucagon and partial agonist
      des-His(1)-[Glu(9)]glucagon amide (glucagon-NH(2)). Alanine substitution in TM
      (transmembrane) helix 2 of Arg(173) or of His(177) detrimentally affected
      glucagon and glucagon-NH(2) response maxima. TM2 receptor mutant, Phe(181)-Ala,
      displayed reduced maximum cAMP accumulation in response to glucagon-NH(2).
      Thr(353)-Cys (TM6) and Glu(406)-Ala (TM7) receptors demonstrated constitutive
      activity and enhanced EC(50) values for glucagon-NH(2); Arg(346)-Ala (TM6) and
      Asn(404)-Ala (TM7) receptors were activated by sub-fmol glucagon concentrations,
      yet were not constitutively active and demonstrated wild-type receptor-like
      EC(50) values for glucagon-NH(2). Unlike Arg(346)-Ala receptors, Thr(353)-Cys,
      Asn(404)-Ala and Glu(406)-Ala receptors demonstrated improved EC(50) values for
      glucagon, whereas their maximal responses to and their affinity for glucagon were
      comparable with the wild-type receptor. In contrast, despite slightly reduced
      glucagon-NH(2) affinity, Arg(346)-Ala, Thr(353)-Cys, Asn(404)-Ala and Glu(406)
      Ala receptors displayed glucagon-NH(2) response maxima that exceeded those seen
      for wild-type receptors. Interestingly, we observed biphasic glucagon-mediated
      signalling responses. Our results are consistent with the concept of different
      agonists promoting the formation of distinct active states from partially active
      R*(low) to fully active R*(high) forms.

PMID- 15506958
TI  - Small GTP-binding protein-coupled receptors.
AB  - Heterotrimeric GPCRs (G-protein-coupled receptors) form the largest group of
      integral membrane receptor proteins and mediate diverse physiological processes.
      In addition to signalling via heterotrimeric G-proteins, GPCRs can also signal by
      interacting with various small G-proteins to regulate downstream effector
      pathways. The small G-protein superfamily is structurally classified into at
      least five families: the Ras, Rho/Rac/cdc42, Rab, Sar1/Arf and Ran families. They
      are monomeric G-proteins with molecular masses over the range 20-30 kDa, which
      function as molecular switches to control many eukaryotic cell functions. Several
      studies have provided evidence of crosstalk between GPCRs and small G-proteins.
      It is well documented that GPCR signalling through heterotrimeric G-proteins can
      lead to the activation of Ras and Rho GTPases. In addition, RhoA, Rabs, ARFs and
      ARF GEFs (guanine nucleotide-exchange factors) can associate directly with GPCRs,
      and GPCRs may also function as GEFs for small GTPases. In this review, we
      summarize the recent progress made in understanding the interaction between GPCRs
      and small GTPases, focusing on understanding how the association of small G
      proteins with GPCRs and GPCR-regulatory proteins may influence GPCR signalling
      and intracellular trafficking.

PMID- 15506960
TI  - The third extracellular loop of G-protein-coupled receptors: more than just a
      linker between two important transmembrane helices.
AB  - GPCRs (G-protein-coupled receptors) are a large family of structurally related
      proteins, which mediate their effects by coupling with G-proteins. Despite
      responding to a range of very diverse stimuli, these receptors exhibit a
      conserved tertiary structure comprising a bundle of seven TM (transmembrane)
      helices linked by alternating ECLs (extracellular loops) and ICLs (intracellular
      loops). The hydrophobic environment formed by the cluster of TM helices is
      functionally important. For example, the 11-cis retinal chromophore of rhodopsin
      forms a protonated Schiff base linkage to a lysine in TM7, deep within the
      helical bundle, and small ligands, such as amine neurotransmitters and non
      peptide analogues of peptide hormones, also bind within the corresponding region
      of their cognate receptors. In addition, activation of GPCRs involves relative
      movement of TM helices to present G-protein interaction sites across the
      intracellular face of the receptor. Consequently, it might be assumed that the
      ECLs of the GPCR are inert peptide linkers that merely connect important TM
      helices. Focusing on ECL3 (third ECL), it is becoming increasingly apparent that
      this extracellular domain can fulfil a range of important roles with respect to
      GPCR signalling, including agonist binding, ligand selectivity and receptor
      activation.

PMID- 15506959
TI  - Participation of RGS8 in the ternary complex of agonist, receptor and G-protein.
AB  - The RGS (regulators of G-protein signalling) protein family sharpen signalling
      kinetics through heterotrimeric G-proteins by enhancing the GTPase activity of
      the G-protein alpha subunit. Paradoxically, they also accelerate receptor
      stimulated activation. We investigated this paradox using the cloned G-protein
      gated K(+) channel as a reporter of the G-protein cycle, and FRET (fluorescence
      resonance energy transfer) between cyan and yellow fluorescent protein tagged
      proteins to detect physical interactions. Our results with the neuronal protein,
      RGS8, show that the enhancement of activation kinetics is a variable phenomenon
      determined by receptor type, G-protein isoform and RGS8 expression levels. In
      contrast, deactivation was consistently accelerated after removal of agonist.
      FRET microscopy revealed a stable physical interaction between RGS8-yellow
      fluorescent protein and G(o) alpha(A)-cyan fluorescent protein that occurred in
      the presence and absence of receptor activation and was not competed away by
      Gbetagamma overexpression. FRET was also seen between RGS8 and Ggamma,
      demonstrating that RGS8 binds to the heterotrimeric G-protein as well as G
      protein alpha subunit-GTP and the transition complex. We propose a novel model
      for the action of RGS proteins on the G-protein cycle involving participation of
      the RGS in the ternary complex: for certain combinations of agonist, receptor and
      G-protein, RGS8 expression improves upon the 'kinetic efficacy' of G-protein
      activation.

PMID- 15506961
TI  - Lipids in health and disease.
AB  - The evidence linking cholesterol levels in the blood to vascular risk is now
      incontrovertible and the introduction of HMG CoA (3-hydroxy-3-methylglutaryl
      coenzyme A) reductase inhibitor (or statin) therapy into clinical practice has
      now revolutionized the management of lipid disorders and silenced at a stroke the
      critics of cholesterol control as a means to vascular disease prevention. Statins
      were the first lipid-lowering agents, which, within a framework of a clinical
      trial, actually extended life by mechanisms that probably go beyond cholesterol
      alone. Their benefits are so impressive that some enthusiasts have been
      emboldened to write that they 'are to atherosclerosis what penicillin was to
      infectious disease'. But is Nature as easily tamed as we might imagine? Some
      individuals show a modest or even poor response to statin therapy. The recent
      discovery of ezetimibe, a highly efficient and precise cholesterol absorption
      inhibitor, has proven to be a very effective cholesterol lowering alternative for
      them and combining statins with ezetimibe, thereby inhibiting cholesterol
      absorption and endogenous synthesis, takes us to realms of cholesterol lowering
      capability that could not have been dreamt of a decade ago.

PMID- 15506962
TI  - Mass spectroscopic analysis of phosphatidylinositol synthesis using 6-deuteriated
      myo-inositol: comparison of the molecular specificities and acyl remodelling
      mechanisms in mouse tissues and cultured cells.
AB  - Mammalian cell PtdIns (phosphatidylinositol) in vivo is enriched in the sn-1
      stearoyl 2-arachidonoyl species, the physiological precursor of
      phosphatidylinositol 4,5-bisphosphate. Mechanisms regulating this specificity are
      unclear but are typically lost for cells in culture. We used ESI-MS (tandem
      electrospray ionization-mass spectrometry) to determine the molecular species of
      PtdIns synthesized by mouse tissues in vivo compared with cultured cells in
      vitro. After incorporation of deuteriated myo-d(6)-inositol over 3 h, endogenous
      and newly synthesized PtdIns and lysoPtdIns species were quantified from
      precursor scans of m/z 241(-) and m/z 247(-) respectively. PtdIns was synthesized
      as a wide range of species irrespective of the final membrane composition.
      Analyses of isotope enrichments argued against acyl remodelling as the major
      regulatory mechanism: composition of the lysoPtdIns pool under all conditions
      reflected that of either endogenous or newly synthesized PtdIns and was always at
      equilibrium. The kinetics of PtdIns synthesis, together with the prolonged time
      scale required for achieving final equilibrium compositions suggest that
      selective transport between membranes and/or hydrolysis of selected molecular
      species are the most probable mechanisms regulating compositions of PtdIns and,
      ultimately, phosphatidylinositol 4,5-bisphosphate.

PMID- 15506963
TI  - Lipidomic analysis of the molecular specificity of a cholinephosphotransferase in
      situ.
AB  - Dynamic lipidomics using ESI-MS (tandem electrospray ionization mass
      spectrometry) of 9-deuterated choline (choline-d(9)) incorporation into mammalian
      cell PtdCho (phosphatidylcholine) permits assessment of the molecular specificity
      of synthesis. Bulk cell PtdCho synthesis occurs in spatially distinct locations,
      using separate CPTs (1,2 diacylglycerol CDP:choline cholinephosphotransferases).
      We assessed whether in vitro molecular selectivity of DAG (diacylglycerol)
      incorporation between CPTs is manifest in situ, by monitoring choline-d(9)
      incorporation into PtdCho and lyso-PtdCho molecular species over 3 h in control
      cells and in CHO-K1 cells overexpressing hCEPT1. Compared with controls, the
      basal molecular species composition of hCEPT1 overexpressors was significantly
      enriched in arachidonate. This was not due to net accretion of cellular PtdCho
      arguing against effects of inadequate unsaturated PtdCho degradation or
      remodelling. Rather, time-course analyses of PtdCho and lyso-PtdCho pools showed
      that both arachidonate-containing DAG incorporation and turnover of PtdCho is
      increased in hCEPT1 overexpressors. Increased choline-d(9) incorporation into
      arachidonyl lyso-PtdCho shows that both phospholipase A(1)- and A(2)-mediated
      turnover is involved. Spatially distinct molecular specificity of DAG
      incorporation into cellular PtdCho at the level of hCEPT1 exists in situ.

PMID- 15506964
TI  - Use of mass spectrometry-based lipidomics to probe PITPalpha
      (phosphatidylinositol transfer protein alpha) function inside the nuclei of
      PITPalpha+/+ and PITPalpha-/- cells.
AB  - The mammalian phospholipid exchange protein PITPalpha (phosphatidylinositol
      transfer protein alpha), found in both extranuclear and endonuclear compartments,
      is thought in part to facilitate nuclear import of the PtdIns
      (phosphatidylinositol) consumed in the generation of proliferation-associated
      endonuclear diacylglycerol accumulations. Unlike phosphatidylcholine, endonuclear
      PtdIns is not synthesized in situ. However, despite progressive postnatal
      lethality of PITPalpha ablation in mice, PITPalpha(-/-) MEF (mouse embryonic
      fibroblasts) lack an obviously impaired proliferative capacity. We used ESI-MS
      (tandem electrospray ionization-MS) to monitor incorporation of the deuterated
      phospholipid precursors, choline-d(9) and inositol-d(6), into molecular species
      of whole cell and endonuclear phosphatidylcholine and PtdIns over 24 h to assess
      the contribution of PITPalpha to the nuclear import of PtdIns into MEF cells. In
      cells labelled for 1, 3, 6, 12 and 24 h fractional inositol-d(6) incorporation
      into whole-cell PtdIns species was consistently higher in PITPalpha(-/-) MEF
      implying greater flux through its biosynthetic pathway. Moreover, endonuclear
      accumulation of PtdIns-d(6) was apparent in the PITPalpha(-/-) cells and mirrored
      that in PITPalpha(+/+) cells. Together, these results suggest that the essential
      endonuclear PtdIns import via PITPalpha can be accommodated by other mechanisms.

PMID- 15506965
TI  - Immunodetection of UCP1 in rat thymocytes.
AB  - Thymi were dissected from rats and connective tissue was removed. Mitochondria
      were purified from isolated thymocytes and immunoblot analysis was performed
      using an antibody specific for uncoupling protein 1, which detected a 32.5 kDa
      protein associated with mitochondria from the thymocytes. This implies that rat
      thymocytes contain uncoupling protein 1.

PMID- 15506966
TI  - Nitric oxide, hypoxia and brain inflammation.
AB  - NO (nitric oxide) acutely and potently inhibits mitochondrial cytochrome oxidase
      in competition with oxygen, thereby raising the apparent K(M) for oxygen of
      mitochondria and neurons into the physiological or pathological range. We find
      that NO from an NO donor or glial inducible NOS (nitric oxide synthase) highly
      sensitizes neurons to hypoxia-induced death, probably via the NO-oxygen
      competition at cytochrome oxidase. Thus the NO from neuronal NOS during
      excitotoxicity or the NO from inducible NOS during inflammation may sensitize the
      brain to hypoxic/ischaemic damage.

PMID- 15506967
TI  - Selective elimination of mitochondria from living cells induced by inhibitors of
      bioenergetic functions.
AB  - The inhibitors of oxidative phosphorylation induced fragmentation of mitochondria
      without any signs of apoptosis in CV-1 and HeLa cells. Prolonged treatment with
      the uncouplers (alone or in combination with the inhibitors of respiration)
      caused perinuclear clusterization of mitochondria, followed by their selective
      elimination. The fraction of mitochondria-depleted cells remained viable.

PMID- 15506968
TI  - Cell-penetrating peptides are excluded from the mitochondrial matrix.
AB  - CPPs (cell-penetrating peptides) facilitate cellular uptake of covalently
      attached macromolecules, through an as yet controversial mechanism that either
      involves direct membrane passage or a type of endocytosis. We investigated the
      potential of the CPPs penetratin and Tat to act as mitochondria-targeting vectors
      by testing whether they were internalized by isolated mitochondria, and by
      mitochondria within cells in culture. We also tested peptides conjugated to the
      mitochondria-targeting moiety triphenylphosphonium. We found no evidence for
      mitochondrial uptake by penetratin, Tat or their triphenylphosphonium conjugates.
      This result suggests that CPPs are unsuitable as mitochondria-targeting vectors,
      and implies an endocytic mode of cellular uptake for CPPs.

PMID- 15506969
TI  - Sab (SH3BP5), a novel mitochondria-localized JNK-interacting protein.
AB  - The JNK (c-Jun N-terminal kinase) pathway is activated by diverse stresses and
      can have an effect on a number of different cellular processes. Protein-protein
      interactions are critical for efficient signalling from JNK to multiple targets;
      through a screen for interacting proteins, we identified a novel JNK-interacting
      protein, Sab (SH3BP5). Sab has previously been found to interact with the Src
      homology 3 domain of Bruton's tyrosine kinase; however, the interaction with JNK
      occurs through a mitogen-activated protein KIM (kinase interaction motif) in a
      region distinct from the Bruton's tyrosine kinase-binding domain. As with c-Jun,
      the presence of this KIM is essential for Sab to act as a JNK substrate.
      Interestingly, Sab is associated with the mitochondria and co-localizes with a
      portion of active JNK after stress treatment. The present study and previously
      reported work may suggest a possible role for Sab in targeting JNK to this
      subcellular compartment and/or mediating crosstalk between different signal
      transduction pathways.

PMID- 15506970
TI  - Study of prostaglandin receptors in mitochondria on apoptosis of human lung
      carcinoma cell line A549.
AB  - PGs (prostaglandins) are synthesized through the cyclo-oxygenase (COX-1 and -2)
      pathway in a variety of cells in response to various physiological stimuli. All
      cells require at least one pathway for apoptosis, and mitochondrial play a
      central role in regulation of apoptosis. In a previous study, incubation of A549
      cells with NS-398 (a COX-2-specific inhibitor) induced apoptosis and inhibited
      cell proliferation, and the concentrations of different PGs between various
      cellular compartments were found to be changed. To determine whether PG receptors
      are involved in this regulation, Western-blot analyses were performed specific
      for PGE(2) (EP receptors) and PGF(2alpha) (FP receptor) receptors, which were
      expressed in A549 cells. Western-blot analysis revealed that mitochondria that
      were isolated from A549 cells expressed EP receptors (EP2, EP3 and EP4), whereas
      FP receptors were undetectable. EP receptors (EP1, EP3 and EP4) and FP receptors
      were detected from A549 cell membrane. These results suggest that the change of
      PG production in A549-cells-induced cancer cell apoptosis might be related to the
      different expressions of EP and FP receptors in cell and mitochondrial membrane.

PMID- 15506971
TI  - Programmed -1 ribosomal frameshifting in the SARS coronavirus.
AB  - Programmed -1 ribosomal frameshifting is an alternate mechanism of translation
      used by coronavirus to synthesize replication proteins encoded by two overlapping
      open reading frames. For some coronaviruses, the mRNA cis-acting stimulatory
      structures involved in this process have been characterized, but their precise
      contribution to ribosomal frameshifting is not completely understood. Recently, a
      novel coronavirus was identified as the causative agent of the severe acute
      respiratory syndrome. This review describes the mRNA motifs involved in
      programmed -1 ribosomal frameshifting in this virus.

PMID- 15506972
TI  - Transcriptional control of Nramp1: a paradigm for the repressive action of c-Myc.
AB  - Slc11a1/Nramp1 (solute carrier family 11 member a1/murine natural resistance
      associated macrophage protein 1 gene) encodes a divalent cation transporter that
      resides within lysosomes/late endosomes of macrophages. Nramp1 modulates the
      cellular distribution of divalent cations in response to cell activation by
      intracellular pathogens. Nramp1 expression is repressed and activated by the
      proto-oncogene c-Myc and Miz-1 (c-Myc-interacting zinc finger protein 1)
      respectively. Here we demonstrate, using a c-Myc mutant (V394D, Val(394)-->Asp)
      that is incapable of binding Miz-1, that c-Myc repression of Nramp1 transcription
      is dependent on its interaction with Miz-1. An oligo pull-down assay demonstrates
      specific binding of recombinant Miz-1 to the Nramp1 Miz-1-binding site or
      initiator element(s), and Miz-1-dependent c-Myc recruitment.

PMID- 15506973
TI  - Post-translational modification of RelA(p65) NF-kappaB.
AB  - Stimulation with diverse agents activates the NF-kappaB (nuclear factor kappaB)
      transcription factor, affecting inflammatory and immune responses, proliferation,
      differentiation, apoptosis and tumourigenesis. Determining how NF-kappaB elicits
      such distinct responses is essential to understanding NF-kappaB function in
      diseased tissues. Recent developments illustrating that post-translational
      modification of NF-kappaB subunits influences their nuclear role are discussed.
      These observations suggest that diagnosis and new therapies based on
      reprogramming NF-kappaB activity could be more efficient than total NF-kappaB
      inhibition.

PMID- 15506974
TI  - Oscillations in transcription factor dynamics: a new way to control gene
      expression.
AB  - Oscillations in second-messenger signalling (e.g. calcium) have previously been
      shown to be important in the control of transcription. More recently,
      oscillations in localization and absolute levels of transcription factors and
      their regulators have been identified. Here we discuss the role of network motifs
      such as the negative feedback loop and their role in oscillatory signalling, and
      how oscillations in components of the nuclear factor kappaB signalling pathway
      are important to the dynamic control of transcription in response to a cytokine
      stimulus.

PMID- 15506975
TI  - Haem oxygenase-1 in inflammation.
AB  - HO-1 (haem oxygenase-1) is a stress-inducible enzyme that plays a protective role
      in inflammation. Pro-inflammatory mediators, including lipopolysaccharide and
      cytokines, induce HO-1 expression. The 5'-flanking region of the HO-1 gene
      contains binding sites for the transcription factors that regulate inflammation,
      including nuclear factor-kappaB and activator protein 1. However, these do not
      appear to mediate lipopolysaccharide-induced HO-1 gene expression. In response to
      haem and antioxidants, murine HO-1 is regulated by the transcription factor Nrf2
      (NF-E2-related factor 2). This transcription factor may also be important in the
      regulation of HO-1 by pro-inflammatory stimuli.

PMID- 15506976
TI  - Epigenetic approaches to cancer therapy.
AB  - Histone deacetylation and DNA methylation have a central role in the control of
      gene expression, including transcriptional repression of tumour suppressor genes.
      Loss of DNA mismatch repair due to methylation of the hMLH1 gene promoter results
      in resistance to cisplatin in vitro and in vivo. The cisplatin-resistant cell
      line A2780/cp70 is 8-fold more resistant to cisplatin than the non-resistant cell
      line, and has the hMLH1 gene methylated. Treatment with an inhibitor of DNA
      methyltransferase, DAC (2-deoxy-5'-azacytidine), results in a partial reversal of
      DNA methylation, re-expression of MLH1 (mutL homologue 1) and sensitization to
      cisplatin both in vitro and in vivo. PXD101 is a novel hydroxamate type histone
      deacetylase inhibitor that shows antitumour activity in vivo and is currently in
      phase I clinical evaluation. Treatment of A2780/cp70 tumour-bearing mice with DAC
      followed by PXD101 results in a marked increase in the number of cells that re
      express MLH1. Since the clinical use of DAC may be limited by toxicity and
      eventual re-methylation of genes, we suggest that the combination of DAC and
      PXD101 could have a role in increasing the efficacy of chemotherapy in patients
      with tumours that lack MLH1 expression due to hMLH1 gene promoter methylation.

PMID- 15506977
TI  - The role of TFIIB conformation in transcriptional regulation.
AB  - Transcription by RNA polymerase II requires the assembly of the general
      transcription factors at the promoter to form a preinitiaiton complex. TFIIB
      (transcription factor IIB) plays a central role in this process, mediating the
      recruitment of RNA polymerase II and positioning it over the transcription start
      site. The assembly of TFIIB at the promoter can be a limiting event and several
      activator proteins have been shown to target TFIIB recruitment in the process of
      transcriptional stimulation. TFIIB is composed of two domains that engage in an
      intramolecular interaction. Indeed, the conformation of TFIIB has been found to
      underpin the function of this general transcription factor. Here we discuss our
      current understanding of TFIIB conformation and its role in transcription
      control.

PMID- 15506978
TI  - The importance of butyrate transport to the regulation of gene expression in the
      colonic epithelium.
AB  - Butyrate is a naturally occurring monocarboxylate, produced in the lumen of the
      colon by microbial fermentation of complex carbohydrates that escape digestion in
      the small intestine. It serves as the principal metabolic fuel for colonic
      epithelial cells, and exerts a variety of effects important to intestinal health
      and function. This brief discussion focuses on the route, role and regulation of
      butyrate transport in the large intestine, with particular emphasis on the
      significance of butyrate transport to the ability of butyrate to modulate
      expression of genes important to the processes maintaining colonic tissue
      homoeostasis.

PMID- 15506979
TI  - In vitro regulation of reporter gene transcription by the androgen receptor AF1
      domain.
AB  - The androgen receptor (AR) is a ligand-activated transcription factor that
      regulates gene expression in response to the steroids testosterone and
      dihydrotestosterone. AR-dependent gene expression is likely to play an important
      role in a number of receptor-associated disorders, such as prostate cancer,
      spinal bulbar muscular atrophy, male type baldness and hirsutism. The AR contains
      two transactivation domains, termed AF1 (activation function 1) located in the N
      terminus and AF2 (activation function 2) in the C-terminal ligand-binding domain.
      AF2 exhibits weak transcriptional activity, whereas AF1 is a strong regulator of
      transcription. Transcriptional regulation by AF1 is thought to be modulated by a
      number of proteins that interact with this region, and by post-translational
      modifications. Our focus is on the N-terminal-interacting proteins and their
      regulation of transcription via interaction with the receptor. To better
      understand the mechanism of AR-AF1 action, we have reconstituted AR activity in
      HeLa nuclear extracts using a unique dual reporter gene assay. Multiple LexA
      binding sites in the promoter allow transcription to be driven by a recombinant
      AR-AF1-Lex fusion protein. The findings from initial experiments suggest an
      increase in transcription initiation and elongation rates by AR-AF1-Lex. The role
      of protein-protein interactions involving co-activators and basal transcription
      factors and AR-AF1 activity are discussed.

PMID- 15506980
TI  - A PLCdelta1-binding protein, p122RhoGAP, is localized in focal adhesions.
AB  - We have investigated the cellular distribution of p122RhoGAP, a GTPase-activating
      protein of Rho small GTPase and an activator of phospholipase C-delta(1).
      Immunofluorescence studies demonstrated that endogenous p122 is localized at the
      tips of actin stress fibres and co-localizes with vinculin in normal rat kidney
      cells. In immunoprecipitation studies, p122 co-precipitated with vinculin,
      indicating that p122 is localized at the sites of focal adhesion. We have also
      shown that the N-terminal half of p122 is responsible for this localization. It
      is conceivable, therefore, that p122 is involved in the reorganization of the
      actin cytoskeleton and focal adhesions that regulate cell-substratum adhesion and
      cell migration.

PMID- 15506981
TI  - Filling the GAPs in cell dynamics control: BPGAP1 promotes cortactin
      translocation to the cell periphery for enhanced cell migration.
AB  - Cells undergo dynamic changes in morphology or motility during cellular division
      and proliferation, differentiation, neuronal pathfinding, wound healing,
      apoptosis, host defense and organ development. These processes are controlled by
      signalling events relayed through cascades of protein interactions leading to the
      establishment and maintenance of cytoskeletal networks of microtubules and actin.
      Various regulators, including the Rho small GTPases (guanine nucleotide
      triphosphatases), serve as master switches to fine-tune the amplitude, duration
      as well as the integration of such circuitry responses. Rho GTPases are activated
      by guanine nucleotide-exchange factors and inactivated by GAPs (GTPase-activating
      proteins). Although normally down-regulating signalling pathways by catalysing
      their GTPase activity, many GAPs exist with various protein modules, the
      functions of which still largely remain unknown. BPGAP1 is a novel RhoGAP that co
      ordinately regulates pseudopodia and cell migration through the interplay of its
      BNIP-2 and Cdc42GAP homology domains serving as a homophilic/heterophilic
      interaction device, an enzymic RhoGAP domain that inactivates RhoA and a proline
      rich region that binds the Src homology-3 domain of cortactin. Both proteins co
      localize to cell periphery and enhance cell migration. As a molecular scaffold in
      cortical actin assembly and organization, cortactin and its interaction with
      small GTPases, GAPs and tyrosine kinases seems set to provide further insights to
      the multiplicity and complexity of cell dynamics control. Elucidating how these
      processes might be individually or co-ordinately regulated through cortactin
      remains an exciting future challenge.

PMID- 15506982
TI  - Control of SCAR activity in Dictyostelium discoideum.
AB  - The WASP (Wiskott-Aldrich syndrome protein)/SCAR (suppressor of cAMP receptor)
      family of adaptor proteins regulate actin polymerization by coupling Rho-family
      GTPases to the activation of the Arp2/3 complex. SCAR exists within a complex of
      proteins, including Nap1 (Nck-associated protein 1), PIR121 (p53-inducible mRNA
      121), Abi2 (Abl-interactor 2) and HSPC300. This complex was first reported to
      inhibit SCAR activity, but there is now some controversy over whether the complex
      is inhibitory or activatory. This complex is currently being studied in a wide
      range of different systems, and model organisms such as the amoeba Dictyostelium
      discoideum have been used to remove genetically SCAR complex members to ascertain
      their specific roles.

PMID- 15506983
TI  - What is in a filopodium? Starfish versus hedgehogs.
AB  - Many cell types can generate thin actin-based protrusive structures, which are
      often classified under the general term of 'filopodia'. However, a range of
      filopodia-like structures exists that differ both morphologically and
      functionally. In this brief review, we discuss the different types of filopodial
      structures, together with the actin-binding proteins and signalling pathways
      involved in their formation. Specifically, we highlight the differences between
      the filopodial extensions induced by the Rho GTPases Cdc42 and Rif.

PMID- 15506984
TI  - The telling tail of L-selectin.
AB  - L-selectin is constitutively expressed on the surface of most leucocytes and is
      important for tethering and subsequent rolling of leucocytes on endothelial
      cells, facilitating their migration into secondary lymphoid organs (e.g. naive T
      cells) and sites of inflammation (e.g. neutrophils). Previous studies have shown
      that the 17-amino-acid L-selectin cytoplasmic tail is important for its function
      in cell adhesion and, hence, identifying binding partners will provide insight
      into how L-selectin is regulated in leucocytes. This review describes currently
      known binding partners of the L-selectin tail and how their associations affect L
      selectin function.

PMID- 15506985
TI  - Annexin A2 expression during cellular differentiation in myeloid cell lines.
AB  - Annexin A2 is a calcium-dependent, phospholipid-binding protein found on many
      cell types. It consists of a short hydrophobic tail (Ser(2)-Asn(32)), which
      dictates its function, and a core domain (Phe(33)-Asp(339)), which is involved in
      phospholipid binding. Annexin A2 has been implicated in a number of biochemical
      processes, including cell proliferation, foetal immune tolerance, ion-channel
      activation, cell-cell interactions and the bridging of membranes. Annexin A2 is
      reported to be a powerful activator of plasminogen and, therefore, is implicated
      in many normal and pathological processes such as haemostasis and metastasis.
      Myeloid cell lines are used, extensively, to study many aspects of cellular
      proliferation, differentiation and function. In the present study, we have used
      flow cytometry and real-time PCR to investigate the role of annexin A2 expression
      in the proliferation and differentiation of a number of myeloid cell lines. The
      results demonstrated that annexin A2 expression was affected when the cells were
      induced to differentiate by stimulation with all-trans-retinoic acid. Annexin A2
      may, therefore, be an important player in cellular differentiation and its
      disorders.

PMID- 15506986
TI  - Lymphocyte activation receptors: new structural paradigms in group V of C-type
      animal lectins.
AB  - The structure-function relationship in group V of C-type animal lectins remains
      incompletely understood despite the new structures of NK (natural killer) cell
      receptors that have been solved recently. Recombinant, soluble forms of rat and
      human NKR-P1 and CD69 that we obtained after in vitro refolding were analysed by
      Fourier transform-ion cyclotron resonance MS and heteronuclear NMR ((1)H-(15)N
      correlation). In NKR-P1, calcium may not be removed by chelating agents because
      of the very high affinity of binding. In CD69, incorporation of calcium causes a
      structural shift in several amino acids important for the interaction with
      carbohydrates. Structural studies have also allowed us to understand an
      interesting preference of these receptors for either linear (NKR-P1) or branched
      (CD69) carbohydrate sequences.

PMID- 15506987
TI  - The aggregation and membrane-binding properties of an alpha-synuclein peptide
      fragment.
AB  - alpha-Synuclein is a 140 amino acid protein, which is associated with presynaptic
      membranes in the brain, and is the major component of protein aggregates produced
      during the progression of many neurodegenerative diseases. It has been shown that
      a central hydrophobic region of alpha-synuclein comprising residues 71-82 is
      required for aggregation of the protein into the fibrillar form found in
      pathogenic aggregates [Giasson, Murray, Trojanowski and Lee (2001) J. Biol. Chem.
      276, 2380-2386]. In the present study, we used (2)H NMR and electron microscopy
      to investigate the aggregation and membrane-binding properties of a synthetic
      peptide corresponding to this region. Results indicate that this region
      associates with phospholipid bilayers but also forms amyloid-like fibrils in the
      absence of lipid membranes.

PMID- 15506988
TI  - Immunoglobulin A1 proteases: a structure-function update.
AB  - IgA1 (immunoglobulin A1) antibodies are the first line of defence against
      microbial pathogens such as Neisseria meningitidis and Haemophilus influenzae.
      However, these bacteria secrete a site-specific protease that is capable of
      cleaving human IgA1 and interacting with other host components. The IgA proteases
      are released by the type V secretion pathway, which involves translocation
      through two membranes and an autolytic, post-translational processing step.
      Results reported recently throw light on the type V secretion pathway and on the
      roles of the multifunctional IgA protease. The IgA1 protease-recognition sequence
      is present within the IgA1 hinge region as well as in the variable sequence
      connecting the IgA1 protease to its translocator domain. Recent results suggest
      that neisserial IgA1 proteases are capable of cleaving substrates lacking the
      classical recognition sequence. This review will cover recent advances in the IgA
      protease field.

PMID- 15506990
TI  - Genome-wide prediction and analysis of function-specific transcription factor
      binding sites.
AB  - DNA-binding transcription factors play a central role in transcription
      regulation, and the annotation of transcription-factor binding sites in upstream
      regions of human genes is essential for building a genome-wide regulatory
      network. We describe methodology to accurately predict the transcription-factor
      binding sites in the proximal-promoter region of function-specific genes. In
      order to increase the accuracy of transcription factor binding-site prediction,
      we rely on recent genome sequence data, known transcription factor binding-site
      matrices, and Gene Ontology biological-function-based gene classification. Using
      TRANSFAC position-frequency matrices, we detected individual and cooperating
      transcription-factor binding sites in proximal promoters of ENSEMBL annotated
      human genes. We used the over representation of detected binding sites in the
      proximal promoters as compared to the second exons to control specificity. We
      confirmed the majority of transcription-factor binding sites predicted in
      proximal promoters of immune-response genes with evidence from existing
      literature. We validated the predicted cooperation between transcription factors
      NF-kappa B and IRF in the regulation of gene expression with microarray
      transcript profiling data and literature-derived protein-protein interaction
      network. We also identified over-represented individual and pairs of
      transcription-factor binding sites in the proximal promoters of each Gene
      Ontology biological-process gene group. Our tools and analysis provide a new
      resource for deciphering transcription regulation in different biological
      paradigms.

PMID- 15506991
TI  - A search tool for identification and analysis of conserved sequence patterns in
      Saccharomyces spp. orthologous promoter.
AB  - We describe a web-based resource to identify, search and analyze sequence
      patterns conserved in the multiple sequence alignments of orthologous promoters
      from closely related / distant Saccharomyces spp. The webtool interfaces with a
      database where conserved sequence patterns (greater than 4 bp) have been
      previously extracted from genome-wide promoter alignments, allowing one to carry
      out user-defined genome-wide searches for conserved sequences to assist in the
      discovery of novel promoter elements based on comparative genomics. The web-based
      server can be accessed at http://www2.imtech.res.in/ anand/sacch_prom_pat.html.

PMID- 15506989
TI  - Uptake of denatured collagen into hepatic stellate cells: evidence for the
      involvement of urokinase plasminogen activator receptor-associated
      protein/Endo180.
AB  - Tissue remodelling is dependent on the integration of signals that control
      turnover of ECM (extracellular matrix). Breakdown and endocytosis of collagen, a
      major component of the ECM, is central to this process. Whereas controlled
      secretion of matrix-degrading enzymes (such as matrix metalloproteinases) has
      long been known to mediate ECM breakdown, it is becoming clear that
      uPARAP/Endo180 (where uPARAP stands for urokinase plasminogen activator receptor
      associated protein) serves as a receptor that mediates endocytosis of collagen by
      several types of cells. In the liver, the stellate cells play a major role in
      turnover of ECM including collagens. These cells synthesize various collagens and
      also produce matrix metalloproteinases. In the present study, we investigated the
      capacity of rat hepatic stellate cells to endocytose and degrade 125I-labelled
      heat-denatured collagen I. It was found that the collagen is efficiently taken up
      and degraded by these cells. Degradation was inhibited by inhibitors of lysosomal
      proteases (leupeptin and E-64d) and the vacuolar proton pump (concanamycin A),
      indicating that it takes place in lysosomes. Furthermore, endocytosed FITC
      labelled collagen was shown to reach late endocytic compartments in which it
      colocalized with LysoTracker (a marker of late endocytic compartments).
      Competition experiments showed that uPA and unlabelled collagen are capable of
      inhibiting binding and uptake of [125I]collagen in a dose-dependent manner.
      Moreover, Western-blot analysis of cell lysate (using a polyclonal rabbit human
      Endo180 antiserum) revealed a single band at 180 kDa. In addition, the antiserum
      was capable of reducing [125I]collagen binding to the cell surface. Finally,
      using two primers designed from the human uPARAP/Endo180 mRNA sequence, the
      expression of uPARAP/Endo180 mRNA was detected by reverse transcriptase-PCR.
      These results together suggest that uPARAP/Endo180 mediates endocytosis of
      collagen in rat liver stellate cells.

PMID- 15506992
TI  - Selecting SNPs for association studies based on population frequencies: a novel
      interactive tool and its application to polygenic diseases.
AB  - Common complex polygenic diseases as autoimmune diseases have not been completely
      understood on a molecular level. While many genes are known to be involved in the
      pathways responsible for the phenotype, explicit causes for the susceptibility of
      the disease remain to be elucidated. The susceptibility to disease is thought to
      be the result of genetic epistatic interactions between common polymorphic genes.
      This polymorphism is mostly caused by single nucleotide polymorphisms (SNPs).
      Human subpopulations are known to differ in the susceptibility to the diseases
      and generally in the distribution of single nucleotide polymorphisms. The here
      presented approach retrieves SNPs with the most divergent frequencies for
      selected human subpopulations to help defining properties for the experimental
      verification of SNPs within defined regions. A web-accessible program
      implementing this approach was evaluated for multiple sclerosis (MS), a common
      human polygenic disease. A link to a summary of data from "The SNP Consortium"
      (TSC) with sex-dependencies of SNPs is available. Associations of SNPs to genes,
      genetic markers and chromosomal loci are retrieved from the Ensembl project. This
      tool is recommended to be used in conjunction with microarray analyses or marker
      association studies that link genes or chromosomal loci to particular diseases.

PMID- 15506993
TI  - Large-scale collection and characterization of promoters of human and mouse
      genes.
AB  - We report the generation and initial characterization of a large-scale collection
      of sequences of putative promoter regions (PPRs) of human and mouse genes. Based
      on our unique collection of 400,225 and 580,209 human and mouse full-length
      cDNAs, we determined exact transcriptional start sites (TSSs). Using positional
      information of the TSSs, we could retrieve adjacent sequences as PPRs for 8,793
      and 6,875 human and mouse genes, respectively. The positions of the PPRs were 4
      kb upstream to previously reported 5'-ends of cDNAs on average, demonstrating
      that full-length cDNA information is indispensable for this purpose. Among those
      PPRs supported by experimentally validated TSSs, 3,324 could be paired as
      mutually homologous genes between human and mouse and were used for the
      comprehensive comparative studies. The sequence identities in the proximal
      regions of the TSSs were 45% on average, and 22,794 putative transcription factor
      binding sites that are conserved between human and mouse were identified. The
      data resource created in the present work and the results of the sequences'
      initial characterization should lay the firm foundation for deciphering the
      transcriptional modulations of human genes. All the data were deposited and made
      available through a database for comparative studies, DBTSS.

PMID- 15506994
TI  - Recognition of remotely related structural homologues using sequence profiles of
      aligned homologous protein structures.
AB  - In order to bridge the gap between proteins with three-dimensional (3-D)
      structural information and those without 3-D structures, extensive experimental
      and computational efforts for structure recognition are being invested. One of
      the rapid and simple computational approaches for structure recognition makes use
      of sequence profiles with sensitive profile matching procedures to identify
      remotely related homologous families. While adopting this approach we used
      profiles that are generated from structure-based sequence alignment of homologous
      protein domains of known structures integrated with sequence homologues. We
      present an assessment of this fast and simple approach. About one year ago, using
      this approach, we had identified structural homologues for 315 sequence families,
      which were not known to have any 3-D structural information. The subsequent
      experimental structure determination for at least one of the members in 110 of
      315 sequence families allowed a retrospective assessment of the correctness of
      structure recognition. We demonstrate that correct folds are detected with an
      accuracy of 96.4% (106/110). Most (81/106) of the associations are made correctly
      to the specific structural family. For 23/106, the structure associations are
      valid at the superfamily level. Thus, profiles of protein families of known
      structure when used with sensitive profile-based search procedure result in
      structure association of high confidence. Further assignment at the level of
      superfamily or family would provide clues to probable functions of new proteins.
      Importantly, the public availability of these profiles from us could enable one
      to perform genome wide structure assignment in a local machine in a fast and
      accurate manner.

PMID- 15506995
TI  - Efficient two-sample designs for microarray experiments with biological
      replications.
AB  - In the last years, biostatistical research has begun to apply linear models and
      design theory to develop efficient experimental designs and analysis tools for
      gene expression microarray data. With two-colour microarrays, direct comparisons
      of RNA-targets are possible and lead to incomplete block designs. In this
      setting, efficient designs for simple and factorial microarray experiments have
      mainly been proposed for technical replicates. But for biological replicates,
      which are crucial to obtain inference that can be generalised to a biological
      population, this question has only been discussed recently and is not fully
      solved yet. In this paper, we propose efficient designs for independent two
      sample experiments using two-colour microarrays enabling biologists to measure
      their biological random samples in an efficient manner to draw generalisable
      conclusions. We give advice for experimental situations with differing group
      sizes and show the impact of different designs on the variance and degrees of
      freedom of the test statistics. The designs proposed in this paper can be
      evaluated using SAS PROC MIXED or S+/R lme.

PMID- 15506996
TI  - A DNA Motif Lexicon: cataloguing and annotating sequences.
AB  - The rapid proliferation of genomic DNA sequences has created a significant need
      for software that can both focus on relatively small areas (such as within genes
      or promoters) and provide wide-zoom views of patterns across entire genomes. We
      present our DNA Motif Lexicon that enables users to perform genome-wide searches
      for motifs of interest and create customizable results pages, where results
      differ in the degree and extent of annotation. Searching for a particular motif
      is akin to a word search in a natural language; our motif lexicon speaks to this
      new time when we will increasingly rely upon DNA dictionaries that offer rich
      types of annotation. Indeed, the concept of "lexomics", introduced in this paper
      may be appropriate to the types of meta-analyses appropriate to the deciphering
      of regulatory information. Currently supporting five genomes, our web-based
      lexicon allows users to look up motifs of interest and build user-defined result
      pages to include the following: (1) all base pair locations where a motif is
      found with links to further search the "neighborhoods" near each of these
      locations; whether each location of the motif is genic (within) a gene,
      intergenic, or a bridging sequence (overlapping a gene boundary) (2) NCBI hot
      links to nearest upstream and downstream genes for each location (3) statistical
      information about the query (4) whether the motif is a certain type of repeat (5)
      links for the reverse, complement and reverse-complement of the motif of interest
      and (6) hot-links to PubMed abstracts which mention the motif of interest. A
      software framework facilitates the continual development of new annotation
      modules. The tool is located at: http://genomics.wheatoncollege.edu/cgi
      bin/lexicon.exe.

PMID- 15506997
TI  - Annotating significant pairs of transcription factor binding sites in regulatory
      DNA.
AB  - In the presented work we search for transcription factor binding sites (BS) by
      including additional information about typical BS patterns. The new proposed
      score combines the ordinary profile score based on TRANSFAC-matrices together
      with a score based on pairs of BS. The latter score positively weights pairs of
      BS that tend to occur together in many regulatory DNA-sequences, in contrast to a
      random background model. The empirical BS pair frequencies result from our
      evaluation of a large dataset of orthologous genes.

PMID- 15506998
TI  - Prediction of IFN-gamma regulated gene transcription.
AB  - IFN-gamma, a cytokine promoting cell-mediated immunity and antiviral effects,
      regulates the expression of a large set of genes involved in the immune response.
      Based on logistic regression, an in silico model for predicting IFN-gamma
      regulated transcription has been developed by scoring the transcription factor
      binding sites on the putative promoters of regulated versus not regulated genes
      derived from the microarray data of IFN-gamma treated human macrophages. The
      model effectively discriminates the transcription factor binding sites that
      confer responsiveness to IFN-gamma from those that do not. The model has 65% true
      positive and 22% false positive rates when evaluated on a small validation set.
      In order to identify potential IFN-gamma regulated genes in the whole genome, the
      model has been used to screen 13,668 promoter pairs of human-mouse
      orthologs/homologs from Ensembl, and 1,387 of them were predicted to be
      potentially regulated by IFN-gamma. In the pilot experiment, the regulation
      pattern of a subset of predicted genes that were not detected by microarray
      approach was evaluated by quantitative PCR. The results for the four novel genes,
      which are up regulated by IFN-gamma in human macrophages and identified by this
      approach, are described in the present communication.

PMID- 15506999
TI  - Web-based visualisation of the transcriptional control network of Escherichia
      coli.
AB  - Transcription is one of the basic processes of gene expression, controlled by a
      complex network of biochemical reactions. Despite its importance, most work on
      the visualisation of biochemical networks focuses on the representation of
      metabolic pathways. The visualisation of the complex networks controlling
      transcription requires the implementation of a hierarchical approach that allows
      the display of the structure of each regulatory region with its transcription
      factors and regulated operons. This paper presents a web-based application for
      the visualisation of transcriptional control networks. It takes as case study the
      organism Escherichia coli. The definition of the visual components implemented is
      mainly based on those proposed by Shen-Orr et al., 2002, slightly extended to
      visualise complex networks.

PMID- 15507000
TI  - In silico exploration of the fructose-6-phosphate phosphorylation step in
      glycolysis: genomic evidence of the coexistence of an atypical ATP-dependent
      along with a PPi-dependent phosphofructokinase in Propionibacterium
      freudenreichii subsp. shermanii.
AB  - We performed a detailed bioinformatic study of the catalytic step of fructose-6
      phosphate phosphorylation in glycolysis based on the raw genomic draft of
      Propionibacterium freudenreichii subsp. shermanii (P. shermanii) ATCC9614
      [Meurice et al., 2004]. Our results provide the first in silico evidence of the
      coexistence of genes coding for an ATP-dependent phosphofructokinase (ATP-PFK)
      and a PPi-dependent phosphofructokinase (PPi-PFK), whereas the fructose-1,6
      bisphosphatase (FBP) and ADP-dependent phosphofructokinase (ADP-PFK) are absent.
      The deduced amino acid sequence corresponding to the PPi-PFK (AJ508922) shares
      100% similarity with the already characterised propionibacterial protein (P29495;
      Ladror et al., 1991]. The unexpected ATP-PFK gene (AJ509827) encodes a protein of
      373 aa which is highly similar (50% positive residues) along at least 95% of its
      sequence length to different well-characterised ATP-PFKs. The characteristic
      PROSITE pattern important for the enzyme function of ATP-PFKs (PS00433) was
      conserved in the putative ATP-PFK sequence: 8 out of 9 amino acid residues.
      According to the recent evolutionary study of PFK proteins with different
      phosphate donors [Bapteste et al., 2003], the propionibacterial ATP-PFK harbours
      a G104-K124 residue combination, which strongly suggested that this enzyme
      belongs to the group of atypical ATP-PFKs. According to our phylogenetic analyses
      the amino acid sequence of the ATP-PFK is clustered with the atypical ATP-PFKs
      from group III of the Siebers classification [Siebers et al., 1998], whereas the
      expected PPi-PFK protein is closer to the PPi-PFKs from clade P [Muller et al.,
      2001]. The possible significance of the co-existence of these two PFKs and their
      importance for the regulation of glycolytic pathway flux in P. shermanii is
      discussed.

PMID- 15507001
TI  - Academic medicine and intercalated degrees.

PMID- 15507002
TI  - Graduate entry medicine: what it is and what it isn't.

PMID- 15507003
TI  - Graduate entry to medical school.

PMID- 15507004
TI  - Accelerated graduate entry programmes: a student's perspective.

PMID- 15507005
TI  - Academic medicine and intercalated degrees--the myth of student choice.

PMID- 15507006
TI  - Revitalising academic medicine: the views of an interested bystander.

PMID- 15507007
TI  - Are differences between graduates and undergraduates in a medical course due to
      age or prior degree?
AB  - BACKGROUND: The number of medical programmes targeted at graduates is increasing
      and there are reports of beneficial outcomes. However, many new graduate medical
      schools have simultaneously changed their admission criteria and curricula. This
      study aimed to determine whether there were differences between graduates and
      undergraduates on the same medical course and to establish which differences
      might be due to having a prior degree, the course itself or age at entry to
      medical school. METHODS: A questionnaire-based survey was administered to all
      students in Years 2-5. It included the Study Process Questionnaire, the
      Achievement Motivation Profile and Likert scale questions on career. RESULTS:
      Questionnaires were completed by 587 students (response rate 80.3%), of whom 143
      had a prior degree. Whilst having a prior degree was associated with many
      outcomes, for most this disappeared, and the overall predictive ability of the
      model improved when age was included. Age at entry to medical school brought
      certainty and motivation about career choice, a prior degree had some effect on
      approaches to studying and co-operativeness, while the course itself had effects
      on most outcomes, some of which were positive and some negative. CONCLUSION:
      Graduates bring a distinct quality to a course but many of these relate to a
      student's age. Older age at entry may be more important than having a prior
      degree.

PMID- 15507008
TI  - Are graduate entry programmes the answer to recruiting and selecting tomorrow's
      doctors?
AB  - OBJECTIVE: In the wake of the introduction of graduate entry programmes, this
      paper aims to promote discussion and debate on student recruitment and selection,
      with a view to achieving a better match between the medical student population
      and the health needs of the population as a whole. SETTING: Government
      initiatives in the UK and Australia have increased the number of medical school
      places, with a substantial proportion allocated to graduate entry students. In
      the UK, a government priority is to widen access to applicants from disadvantaged
      areas and lower socio-economic groups. In Australia, additional concerns for the
      government include ensuring medical services for rural and remote areas and
      improving indigenous health. At the same time, the governments in both countries
      are shifting costs in the direction of a 'user pays' system. OUTCOME: Graduate
      entry programmes represent a particular approach to minimising the effects of
      disadvantage, increasing the representation of students from diverse backgrounds,
      achieving a better match between the medical student population and the general
      population, and encouraging more flexible and inclusive selection and admissions
      policies. They also have certain disadvantages. It is possible to define a set of
      principles to increase the diversity of the medical school class with respect to
      both academic and personal qualities, whether in undergraduates or in graduate
      entrants. CONCLUSIONS: Graduate entry programmes can contribute to increased
      student diversity, but are unlikely to have much impact without other strategies
      to reinforce this aim. A nationwide collaboration could provide opportunities for
      research to establish more efficient and effective ways of selecting tomorrow's
      doctors.

PMID- 15507009
TI  - Anxiety in medical students: is preparation for full-time clinical attachments
      more dependent upon differences in maturity or on educational programmes for
      undergraduate and graduate entry students?
AB  - INTRODUCTION: The transition to full-time clinical studies holds anxieties for
      most medical students. While graduate entry medical education has only recently
      begun in the UK, the parallel undergraduate and graduate entry MBBS courses
      taught at our school allowed us to study how 2 differently prepared groups
      perceived this vital time at a comparable stage in their training. METHOD: An
      anonymous questionnaire collected demographic data and graded anxiety in 13
      statements relating to starting full-time clinical attachments. Two open
      questions allowed free text comment on the most positive and negative influences
      perceived during this time. Both a statistical analysis and a qualitative
      assessment were performed to compare the 2 groups of students. RESULTS: The 2
      groups were similar with respect to gender but the graduate entry students were
      significantly older. The graduate entry students were significantly less anxious
      about most aspects of the transition period compared to the undergraduates. These
      course differences remained after adjusting for age and sex. When adjusted for
      course and age, male students expressed less anxiety. The main positive
      qualitative statements related to continual clinical and communication skills
      training in the graduate entry group. The main qualitative concerns in both
      groups related to 'fitting in' and perceived lack of factual knowledge.
      DISCUSSION: These data support the early introduction of clinical skills
      teaching, backed up by a fully integrated clinically relevant curriculum with
      continued assessment, in preparing students and reducing levels of anxiety before
      they start full-time clinical attachments. These course design differences appear
      to be more important than any differences in maturity between the 2 groups.

PMID- 15507010
TI  - Prior academic background and student performance in assessment in a graduate
      entry programme.
AB  - OBJECTIVES: This study aims to identify whether non-science graduates perform as
      well as science graduates in Basic and Clinical Sciences (B & CS) assessments
      during Years 1-3 of a four-year graduate-entry programme at the University of
      Sydney (the 'USydMP'). METHODS: Students were grouped into five categories:
      Health Professions (HP), Biomedical Sciences (BMS), Other Biology (BIOL),
      Physical Sciences (PHYS) or Non-Science (NONS). We examined the performance rank
      of students in each of the five groups for single best answer (SBA) and modified
      essay (MEQ) assessments separately, and also calculated the relative risk of
      failure in the summative assessments in Years 2 and 3. RESULTS: Students with
      science-based prior degrees performed better in the SBA assessments. The same
      occurred initially in the MEQs, but the effect diminished with time. The HP
      students performed consistently better but converged with other groups over time,
      particularly in the MEQs. Relative performance by the NONS students improved with
      time in both assessment formats. Overall, differences between the highest and
      lowest groups were small and very few students failed to meet the overall
      standard for the summative assessments. HP and BMS students had the lowest
      failure rate. NONS students were more likely to fail the assessments in Year 2
      and 3, but their pass rates were still high. Female students performed
      significantly better overall at the end of Year 2 and in Year 3. There were only
      minor differences between Australian resident and International students.
      CONCLUSION: While there are small differences in performance in B & CS early in
      the programme, these lessen with time. The study results will inform decisions
      regarding timing of summative assessments, selection policy and for providing
      additional support to students who need it to minimize their risk of failure.
      Readers should note that this paper refers to student performance in only one of
      the four curriculum themes, where health professional and science graduates would
      be expected to have a significant advantage.

PMID- 15507011
TI  - Models for the development of graduate entry medical courses: two case studies.
AB  - INTRODUCTION: The introduction of graduate entry medical courses requires
      attention to models of decision-making and change. Much of the educational
      literature describes change as either centralised or decentralised with the
      latter claimed to be more effective. Recently Fullan has argued for the
      importance of an ongoing culture of change. This paper examines the change
      culture of two medical schools adopting graduate entry courses; Flinders
      University in South Australia and St George's Hospital Medical School, London.
      METHOD: Comparative case study was used. Key informants were interviewed and
      documents and records analysed. Data were cross-checked and categorised to
      generate models of change. RESULTS: There were four components of the change
      culture at Flinders but they were not sufficient on their own to generate change.
      The process was triggered by a significant external event. The nature of the
      change was also important. The descriptive model developed suggested a complex
      interplay of factors rather than attributing the success of the change to the
      change mechanisms adopted alone. The model was tested for explanatory potential
      at St George's. The culture there was described as both 'macro-innovative' and
      'micro-conservative'. External events were also important but they exerted a
      positive force. A more centralised approach was adopted. DISCUSSION: The models
      developed represent change as 'dynamic, complex and open' rather than a simple
      centralised or decentralised dichotomy. While some of the elements of a change
      culture were evident at both schools there were longer term questions of
      sustainability. This has implications for development of all programmes but
      particularly for graduate entry schools.

PMID- 15507012
TI  - The long case.
AB  - BACKGROUND: The long case has been gradually replaced by the objective structured
      clinical examination (OSCE) as a summative assessment of clinical skills. Its
      demise occurred against a paucity of psychometric research. This article reviews
      the current status of the long case, appraising its strengths and weaknesses as
      an assessment tool. ISSUES: There is a conflict between validity and reliability.
      The long case assesses an integrated clinical reaction between doctor and real
      patients and has high face validity. Intercase reliability is the prime problem.
      As most examinations traditionally used a single case only, problems of content
      specificity and standardisation were not addressed. DISCUSSION: Recent research
      suggests that testing across more cases does improve reliability. Better
      structuring of tests and direct observation increases validity. Substituting
      standardised cases for real patients may be of little benefit compared to
      increasing the sample of cases. CONCLUSIONS: Observed long cases can be useful
      for assessment depending on the sample size of cases and examiners. More research
      is needed into the exact nature of intercase and interexaminer variance and
      consequential validity. Feasibility remains a key problem. More exploration of
      combined assessments using real patients with OSCEs is suggested.

PMID- 15507015
TI  - Teaching cardiac auscultation without patient contact.

PMID- 15507016
TI  - Interactive, web-based e-lectures with a multimedia online examination.

PMID- 15507017
TI  - An Acrobat-based program for gross anatomy revision.

PMID- 15507018
TI  - Educational imperatives drive technological advancement in the surgery clerkship.

PMID- 15507019
TI  - Cinematic clinical psychiatric cases in graduate medical education.

PMID- 15507020
TI  - A novel approach to faculty development programme evaluation.

PMID- 15507021
TI  - Introducing peer evaluation during tutorial presentation.

PMID- 15507022
TI  - Registrars are teachers too!

PMID- 15507023
TI  - Exploring professional values and health policy through Photovoice.

PMID- 15507025
TI  - Rowing towards leadership and teambuilding.

PMID- 15507024
TI  - Designing a surgical 'resident-as-teacher' programme.

PMID- 15507026
TI  - Summer research training programme in health care disparities.

PMID- 15507027
TI  - Oversight of medical education research.

PMID- 15507028
TI  - A rapid clerkship redesign to address new realities.

PMID- 15507029
TI  - A PBL-based structured genetic curriculum.

PMID- 15507030
TI  - Integrating experiential learning in complementary and alternative medicine.

PMID- 15507031
TI  - Interacting factors of students' perceptions on an effective curriculum.

PMID- 15507032
TI  - Designing health plan benefits: a simulation exercise.

PMID- 15507034
TI  - Medical student peer group utilisation of clinical scenarios.

PMID- 15507033
TI  - Integrating HIV risk reduction into the medical curriculum.

PMID- 15507035
TI  - Developing clinical skills: a simple and practical tool.

PMID- 15507036
TI  - The objective structured video examination of medical students.

PMID- 15507037
TI  - The story in medicine: skills for MDs.

PMID- 15507038
TI  - Medical students, deaf patients and cancer.

PMID- 15507039
TI  - Outcomes-based education versus coping with complexity: should we be educating
      for capability?

PMID- 15507041
TI  - Justifications for learning outcomes: more appropriate educational theories.

PMID- 15507040
TI  - Poor English skills as a barrier for Japanese health care professionals in
      learning and practising evidence-based medicine.

PMID- 15507042
TI  - Globalization, internationalization and nursing.

PMID- 15507044
TI  - Factors in care management affecting client outcomes in home care.
AB  - The purpose of the present study was to identify which factors in care management
      affect client outcomes. We performed path analysis using care management
      processes as independent variables, and client outcomes measures as dependent
      variables. Client outcomes were measured by improvement in care items and
      Functional Independence Measure (FIM) scores in 170 clients, and client
      satisfaction in 97 clients. Improvement in care items was significantly related
      to the amount of service. Deterioration of the functional independence level was
      significantly related to the amount of service and lower implementation of
      monitoring. Higher implementation of evaluation raised client satisfaction. It is
      important for care managers to develop a care plan based on the necessary amount
      of service and to perform monitoring. A sufficient amount of service in the care
      plan and higher implementation of monitoring and evaluation are the three factors
      in care management affecting client outcomes.

PMID- 15507045
TI  - Validating the revised Health Belief Model for young families: implications for
      nurses' health promotion practice.
AB  - By modifying the Health Belief Model (HBM) nurses can provide health promotion
      guidance for families through the revised HBM for young families. The constructs
      'perceived behavioral control' and 'behavioral intention' from Ajzen's Theory of
      Planned Behavior were added to the HBM to provide a health orientation. An
      initial qualitative study informed the second quantitative study through thematic
      data obtained by interviewing parents about family health. The second comparative
      study of low and high socioeconomic status families of preschool-aged children
      living in western Sydney, Australia, measured family health through the Parental
      Health Behavior Questionnaire (PHBQ). After a small pilot study, the researcher
      distributed 150 questionnaires to center directors from preschools, kindergartens
      and long day care, who then handed out questionnaires to interested parents. Data
      collection occurred in 1998 with consenting parents returning the questionnaires
      for collection by the researchers. A convenience sample of 103 was obtained with
      a 69% return rate. Analysis was undertaken through MANCOVA. Justification for
      validity occurred through logical analysis and hypothesis testing, based on the
      literature, while reliability was acknowledged by undertaking Cronbach
      coefficient alphas on small variable clusters. Results support the constructs
      'perceived behavioral control' and 'behavioral intention' in the revised model,
      suggesting that for families of different socioeconomic background, differences
      emerge in terms of their perceived control over their child's health and the
      initiation of health behaviors for their child. Recommendations for further
      research are for refinement of the PHBQ, new research with different families,
      and further testing of all the model constructs.

PMID- 15507046
TI  - Nursing culture of an operating theater in Italy.
AB  - Sociocultural and organizational factors that influence the work culture of
      nurses in an Italian operating theater were the subject of the present
      qualitative explorative study. Italy is one of the world's wealthiest, most
      powerful countries. Yet little is known outside its borders about the unique
      culture of Italian nurses at work in hospitals and its effect on health care.
      Throughout this Japanese author's first hand experience of the microculture of
      Italian nursing, using a microethnographic design with focus groups for cultural
      interpretation, data were collected during 2000-2001 from 25 staff nurses working
      full-time in one regional hospital. Nurses in the operating theater, considerably
      less educated than doctors and accustomed to the power and status of medicine,
      were directed in nearly all activities by physicians. Finding little leadership
      from management, the nurses developed solid defenses against change and conflict
      through concerted allegiance to one another. The findings suggest that with
      Italian nurses questioning tradition and seeking university education, there may
      be gradual recognition by medicine, management and the public of their
      contribution to health system performance, improved patient care outcomes, and
      the value of the nursing profession.

PMID- 15507047
TI  - Assessment of patient satisfaction of mentally ill patients hospitalized in
      Thailand.
AB  - Psychiatric patients' satisfaction with their hospital care has not been reported
      in the Western literature. The concept of asking psychiatric patients about their
      perceptions of care is relatively new. The purpose of the present investigation
      was to assess the satisfaction of the care received by a group of acutely
      mentally ill hospitalized Thai patients. This post-test design examined a random
      sample of 182 persons hospitalized between 1 March 2000 and 31 July 2000. Using a
      validated Perception of Care instrument, research assistants assessed patient
      satisfaction. Patients rated the care as average with none of the items achieving
      a very good or excellent score. The lowest scoring items were receiving
      information about their rights, consistency of information provided, and the ease
      of obtaining information. Women tended to be more satisfied with care as were
      patients over the age of 55 years (P = 0.02). Patients with a diagnosis of
      schizophrenia were more satisfied with the care than other patients (P = 0.05).
      It is unknown if satisfaction levels are similar in other institutions in
      Thailand. None of the areas received excellent or very good ratings. The findings
      of this study were shared with the staff at the study site. There appears to be a
      need to develop performance improvement activities designed to address the areas
      identified as needing improvement. Replication of this study in other Thailand
      sites would provide an opportunity for agencies to benchmark their findings. By
      consenting to be a part of this study the staff and patients have taken a
      positive step forward to improve patient satisfaction with care.

PMID- 15507048
TI  - Client supervision: meaning and experiences from the perspective of Norwegian
      public health nurses.
AB  - The aim of the present study was to examine the meaning and experiences of client
      supervision from the perspective of Norwegian public health nurses. The World
      Health Organization (WHO) states that new intervention strategies to improve
      public health are necessary. Supervision represents such a strategy. Three focus
      groups were interviewed twice. The data were analyzed by qualitative content
      analysis. The findings revealed three themes: (i) the meaning of the umbrella
      term client supervision; informing, teaching, giving advice and ensuring the
      quality of supervision; (ii) factors influencing supervision; the public health
      nurses' available time and competence and the clients' ability to be supervised;
      and (iii) events and content representing the complexity of conducting
      supervision. In conclusion, the width of the concept, the influencing factors and
      the complexity claim that public health nurses have competence to supervise.

PMID- 15507049
TI  - Support network of adolescents with chronic disease: adolescents' perspective.
AB  - The purpose of this study was to describe the support network of adolescents with
      a chronic disease from their own perspective. Data were collected by interviewing
      adolescents with asthma, epilepsy, juvenile rheumatoid arthritis (JRA) and
      insulin-dependent diabetes mellitus (IDDM). The sample consisted of 40
      adolescents aged between 13 and 17 years. Interview data were examined using
      content analysis. Six main categories were established to describe the support
      network of adolescents with a chronic disease: parents, peers, school, health
      care providers, technology and pets. Peers were divided into two groups: fellow
      sufferers and peers without a chronic disease. At school, teachers, school nurses
      and classmates were part of the support network. Health care providers included
      nurses, physicians and physiotherapists. Technology was also part of the support
      network and included four techniques that may be used to communicate: computers,
      mobile telephones, television and videos. The results provided a useful insight
      into the social network of adolescents with chronic disease and serve to raise
      awareness of the problems and opinions experienced by adolescents with this
      condition.

PMID- 15507050
TI  - Case for blending pedigrees, genograms and ecomaps: nursing's contribution to the
      'big picture'.
AB  - In the 21st century, knowledge of genetics is closely linked to the ability to
      provide good care for all patients, not just the few with uncommon genetic
      diseases. The authors suggest that what is needed in nursing is a comprehensive,
      three generation pedigree that records a patient's medical, social and
      environmental history, thereby communicating a 'big picture' scenario for
      holistic nursing care. The case is made for blending pedigrees, genograms and
      ecomaps. Such a tool can guide risk factor identification and inform patient and
      family clinical decisions vis-a-vis care management strategies, psychosocial
      support and education for reproductive decisions, risk reduction, and the
      prevention, screening, diagnosis, referral and long-term management of disease.
      Pedigrees, genograms and ecomaps are defined, and their clinical application and
      reliability are described. A case example that blends these tools is presented.
      Ethical, legal, educational and research implications are discussed.

PMID- 15507051
TI  - Diet and health: nursing perspective for the health of our aging population.
AB  - For most age-related disorders there is no cure, and treatment is expensive and
      often ineffective. Thus, disease prevention is an issue of increasing concern and
      importance. Nurses form the largest professional healthcare group in the world,
      and the professional code of the modern day nurse advocates health promotion as a
      primary role. Nurses, by virtue of their close, direct interaction with their
      community and clients, are in a strong position to disseminate and reinforce the
      message of health promotion with the aim of achieving functional longevity in our
      aging population. This requires that nurses themselves increase their awareness,
      knowledge and understanding of relevant interdisciplinary research findings. In
      the current review, the influence of diet on the risk of four of the most
      prevalent age-related diseases (cancer, cardiovascular disease, dementia and
      diabetes) is presented, and the underlying mechanisms of influence are discussed,
      with particular focus on antioxidant-rich foods.

PMID- 15507052
TI  - Women's views and experiences of outpatient hysteroscopy: implications for a
      patient-centered service.
AB  - This study examined women's views and experiences of an invasive outpatient
      procedure and was undertaken in the context of the UK Government's policy of
      developing a patient-centered service. The research was based on a consecutive
      series of 30 attendees for outpatient hysteroscopy at a London hospital. Pain was
      recorded using linear analog scales, qualitative semistructured interviews were
      undertaken and a diary was completed for 3 days following the procedure. Overall
      pain ratings for 13 women (45%) were classified as a medium to high score.
      However, nearly all women preferred a future outpatient procedure. A range of
      factors influenced this preference, including their ability to cope with the
      pain, the reduced anxiety associated with undergoing the procedure immediately, a
      dislike of general anesthetics and the convenience of not disrupting usual
      routines. The psychosocial aspects of care were also identified as important in
      assisting women to cope, and form a key factor influencing patient's evaluation
      of services.

PMID- 15507053
TI  - Perceptions of professional clinicians and non-clinicians on their involvement in
      strategic planning in health care management: implications for interdisciplinary
      involvement.
AB  - Abstract There is increasing emphasis on interdisciplinary involvement by health
      care managers. The objective of the present paper was to identify the level of
      involvement that middle manager heads of department have in strategy development
      in acute care hospitals in Ireland, and to identify if professional clinicians
      were more involved than non-clinicians. Twenty-five interviews were undertaken.
      Findings indicated that middle managers were strategically involved and that non
      clinicians perceived that they were more involved in strategy development than
      professional clinicians. Strategic involvement appeared to result from a higher
      level of strategic awareness and confidence by non-clinicians in the process.
      Professional clinicians perceived that their expertize was not recognized or
      appreciated by non-clinicians or by senior management. Agreement of strategy
      amongst both groups is critical, as exclusion will lead to demotivation and
      consequent deterioration in health care delivery.

PMID- 15507054
TI  - Effect of person-centered showering and the towel bath on bathing-associated
      aggression, agitation, and discomfort in nursing home residents with dementia: a
      randomized, controlled trial.
AB  - OBJECTIVES: To evaluate the efficacy of two nonpharmacological techniques in
      reducing agitation, aggression, and discomfort in nursing home residents with
      dementia. The techniques evaluated were person-centered showering and the towel
      bath (a person-centered, in-bed bag-bath with no-rinse soap). DESIGN: A
      randomized, controlled trial, with a usual-care control group and two
      experimental groups, with crossover. SETTING: Nine skilled nursing facilities in
      Oregon and six in North Carolina. PARTICIPANTS: Seventy-three residents with
      agitation during bathing (69 completed the trial) and 37 nursing assistants who
      bathed them. MEASUREMENTS: Agitation and aggression were measured using the Care
      Recipient Behavior Assessment; discomfort was measured using a modification of
      the Discomfort Scale for Dementia of the Alzheimer Type. Raters who were blinded
      to subject status coded both from videotaped baths. Secondary measures of effect
      included bath duration, bath completeness, skin condition, and skin microbial
      flora. RESULTS: All measures of agitation and aggression declined significantly
      in both treatment groups but not in the control group, with aggressive incidents
      declining 53% in the person-centered shower group (P<.001) and 60% in the towel
      bath group (P<.001). Discomfort scores also declined significantly in both
      intervention groups (P<.001) but not in the control group. The two interventions
      did not differ in agitation/aggression reduction, but discomfort was less with
      the towel bath (P=.003). Average bath duration increased significantly (by a mean
      of 3.3 minutes) with person-centered showering but not with the towel bath.
      Neither intervention resulted in fewer body parts being bathed; both improved
      skin condition; and neither increased colonization with potentially pathogenic
      bacteria, corynebacteria, or Candida albicans. CONCLUSION: Person-centered
      showering and the towel bath constitute safe, effective methods of reducing
      agitation, aggression, and discomfort during bathing of persons with dementia.

PMID- 15507055
TI  - Bathing disability in community-living older persons: common, consequential, and
      complex.
AB  - OBJECTIVES: To identify the specific bathing subtasks that are affected in
      community-living-older persons with bathing disability and to determine the self
      reported reasons for bathing disability. DESIGN: Cross-sectional study. SETTING:
      General community of greater New Haven, Connecticut. PARTICIPANTS: A total of 626
      community-living persons, aged 73 and older, who completed a comprehensive
      assessment, including a detailed evaluation of bathing disability. MEASUREMENTS:
      Trained research nurses assessed bathing disability (defined as requiring
      personal assistance or having difficulty washing and drying the whole body), the
      specific bathing subtasks that were affected, and the main reasons (up to three)
      for bathing disability. RESULTS: Disability in bathing was present in 195 (31%)
      participants; of these, 97 required personal assistance (i.e., dependence), and
      98 had difficulty bathing. Participants with bathing disability reported a mean+/
      standard deviation of 4.0+/-2.4 affected subtasks. The prevalence rate of
      disability for the eight prespecified bathing subtasks ranged from 25% for taking
      off clothes to 75% for leaving the bathing position. The majority of participants
      (59%) provided more than one reason for bathing disability. The most common
      reasons cited by participants for their bathing disability were balance problems
      (28%), arthritic complaints (26%), and fall or fear of falling (23%). CONCLUSION:
      For community-living older persons, disability in bathing is common, involves
      multiple subtasks, and is attributable to an array of physical and psychological
      problems. Preventive and restorative interventions for bathing disability will
      need to account for the inherent complexity of this essential activity of daily
      living.

PMID- 15507056
TI  - What constitutes normal hemoglobin concentration in community-dwelling disabled
      older women?
AB  - OBJECTIVES: To examine the associations between hemoglobin (Hb) concentration and
      (1) 5-year all-cause mortality and (2) serum erythropoietin (EPO), as the basis
      for the identification of data-driven thresholds, and to assess the clinical
      relevance of mildly low Hb. DESIGN: Prospective study. SETTING: Population based.
      PARTICIPANTS: Community-dwelling women aged 65 and older with moderate-to-severe
      disability--Women's Health and Aging Study I, Baltimore, Maryland, 1992-2000.
      METHODS: Proportional hazards regression was used to model the relationship
      between baseline Hb (available for 686 subjects) and time to death. A generalized
      linear model was used to assess the cross-sectional association between Hb and
      EPO in 641 subjects. RESULTS: A curvilinear slope of steady mortality decrease up
      to the Hb threshold of 13.9 g/dL was observed. Hb of 11 g/dL was independently
      associated with greater mortality than the World Health Organization (WHO) low
      normal cutoff of Hb of 12 g/dL (hazard ratio (HR)=1.2, 95% confidence interval
      (CI)=1.1-1.4), whereas Hb of 14 g/dL was linked to 24% lower mortality (HR=0.76,
      95% CI=0.63-0.92), after comprehensive adjustment for major health status and
      disease-burden indicators. A curvilinear, statistically significant slope of
      steady EPO decrease with increasing Hb up to the threshold of 14.3 g/dL was
      consistently observed. CONCLUSION: The meaningfully lower mortality risk with
      higher Hb levels provides empirical evidence against the notion that Hb currently
      perceived as mildly low is clinically benign. Furthermore, the mortality risk
      gradient observed even within the WHO normal Hb range suggests that Hb levels
      higher than what is currently recommended might offer clinical advantage. The
      relationship between Hb and EPO provided supporting physiological evidence for
      this hypothesis.

PMID- 15507057
TI  - Preparing patients and caregivers to participate in care delivered across
      settings: the Care Transitions Intervention.
AB  - OBJECTIVES: To test whether an intervention designed to encourage older patients
      and their caregivers to assert a more active role during care transitions can
      reduce rehospitalization rates. DESIGN: Quasi-experimental design whereby
      subjects receiving the intervention (n=158) were compared with control subjects
      derived from administrative data (n=1,235). SETTING: A large integrated delivery
      system in Colorado. PARTICIPANTS: Community-dwelling adults aged 65 and older
      admitted to the study hospital with one of nine selected conditions.
      INTERVENTION: Intervention subjects received tools to promote cross-site
      communication, encouragement to take a more active role in their care and assert
      their preferences, and continuity across settings and guidance from a transition
      coach. MEASUREMENTS: Rates of postdischarge hospital use at 30, 60, and 90 days.
      Intervention subjects' care experience was assessed using the care transitions
      measure. RESULTS: The adjusted odds ratio comparing rehospitalization of
      intervention subjects with that of controls was 0.52 (95% confidence interval
      (CI)=0.28-0.96) at 30 days, 0.43 (95% CI=0.25-0.72) at 90 days, and 0.57 (95%
      CI=0.36-0.92) at 180 days. Intervention patients reported high levels of
      confidence in obtaining essential information for managing their condition,
      communicating with members of the healthcare team, and understanding their
      medication regimen. CONCLUSION: Supporting patients and caregivers to take a more
      active role during care transitions appears promising for reducing rates of
      subsequent hospitalization. Further testing may include more diverse populations
      and patients at risk for transitions who are not acutely ill.

PMID- 15507058
TI  - Patient relocation in the 6 months after hip fracture: risk factors for
      fragmented care.
AB  - OBJECTIVES: To describe the incidence and patterns of patient relocation after
      hip fracture, identify factors associated with relocation, and examine effect of
      relocation on outcomes. DESIGN: Prospective cohort study. SETTING: Four hospitals
      in the New York metropolitan area. PARTICIPANTS: A total of 562 patients
      hospitalized for hip fracture discharged alive in 1997 to 1998. MEASUREMENTS:
      Patient characteristics and hospital course were ascertained using patient or
      surrogate interview, research nurse assessment, and medical record review.
      Patient location was ascertained at five time points using patient or surrogate
      interview, and hospital readmissions were identified using New York state and
      hospital admission databases. Mobility was measured using patient or surrogate
      report using the Functional Independence Measure. RESULTS: During 6 months of
      follow-up, the mean number of relocations per patient+/-standard deviation was
      3.5+/-1.5 (range 2-10). Forty-one percent of relocations were between home and
      hospital, 36% between rehabilitation or nursing facility and hospital, 17%
      between rehabilitation or nursing facility and home, and 4% between two
      rehabilitation/nursing facilities. In a Poisson regression model that controlled
      for patient characteristics, hospital course, and length of follow-up, factors
      associated with relocation (P<.05) were absence of dementia, in-hospital
      delirium, one or more new impairments at hospital discharge, hospital discharge
      other than to home, and not living at home alone prefracture. Relocation was not
      significantly associated with immobility or mortality at 6 months (odds
      ratio=1.14, 95% confidence interval=0.97-1.35). CONCLUSION: Subgroups of patients
      with elevated risk of relocation after hip fracture may be target groups for
      intensive care coordination and care planning interventions.

PMID- 15507059
TI  - Safety and efficacy of risedronate in reducing fracture risk in osteoporotic
      women aged 80 and older: implications for the use of antiresorptive agents in the
      old and oldest old.
AB  - OBJECTIVES: To determine the efficacy of risedronate in reducing vertebral
      fracture risk in women aged 80 and older with osteoporosis. DESIGN: Pooled
      analysis of data from three randomized, double-blind, controlled, 3-year-fracture
      endpoint trials conducted from November 1993 to April 1998: Hip Intervention
      Program (HIP), Vertebral Efficacy with Risedronate Therapy-Multinational (VERT
      MN), and VERT-North America (NA). SETTING: Office-based practices, research
      centers, and osteoporosis clinics in Europe, North America, and Australia.
      PARTICIPANTS: Osteoporotic (femoral neck bone mineral density T-score < -2.5
      standard deviations or at least one prevalent vertebral fracture) women aged 80
      and older. INTERVENTION: Patients received placebo (n=688) or risedronate 5 mg/d
      (n=704) for up to 3 years. All patients received 1,000 mg/d calcium and, if
      baseline levels were low, up to 500 IU/d vitamin D. MEASUREMENTS: Cumulative
      incidence of new vertebral fractures. RESULTS: After 1 year, the risk of new
      vertebral fractures in the risedronate group was 81% lower than with placebo (95%
      confidence interval=60-91%; P<.001). The number of women who needed to be treated
      to prevent one new vertebral fracture after 1 year was 12. This early onset of
      efficacy was consistent across the clinical programs, and antifracture efficacy
      was confirmed over 3 years. Risedronate was well tolerated, with a safety profile
      comparable with that of placebo. CONCLUSION: These findings provide the first
      evidence that, even in the very old, reducing bone resorption rate remains an
      effective treatment strategy for osteoporosis. Because each therapeutic agent
      used for the treatment of osteoporosis may have unique characteristics, the
      observations made in this study should not be assumed to apply to other
      bisphosphonates.

PMID- 15507060
TI  - Biomechanical properties of shoes and risk of falls in older adults.
AB  - OBJECTIVES: To determine the relationships between the biomechanical properties
      of shoes worn in a cohort of healthy older adults and the risk of falling.
      DESIGN: Nested case-control study, comparing biomechanical measurements of shoes
      worn by those who reported a fall with measurements of shoes worn by age- and sex
      matched nonfallers engaged in broadly similar activities. SETTING: On-site
      measurements where falls occurred. PARTICIPANTS: A cohort of 1,371 older adults,
      of whom 327 reported a fall and 327 served as age- and sex-matched controls.
      MEASUREMENTS: Shoe measurements related to lateral stability (heel height and
      width, critical tipping angle), foot position sense (heel-collar height, sole
      thickness, and sole flexibility), and the shoe/surface interface (foresole
      material, shoe-to-ground coefficient of friction, sole contact area). RESULTS:
      Greater heel height was associated with increased risk of a fall (P for
      trend=.03), whereas greater sole contact area was associated with reduced risk (P
      for trend=.005). Shoe characteristics related to foot position sense bore little
      apparent relation to fall risk. Coefficients of friction of 0.5 or greater were
      observed in 93% of shoes measured, indicating that very few were excessively
      slippery. CONCLUSION: Certain measurable properties of shoes were found to be
      significantly related to risk of falls in older adults. Wearing shoes with low
      heels and large contact area may help older adults reduce the risk of a fall in
      everyday settings and activities.

PMID- 15507061
TI  - Inappropriate medication administration to the acutely ill elderly: a nationwide
      emergency department study, 1992-2000.
AB  - OBJECTIVES: To determine the national rate and trend of inappropriate medication
      administration to elderly emergency department (ED) patients. Secondary
      objectives were to identify risk factors for receiving an inappropriate
      medication and to determine whether administration is sometimes justified based
      on diagnosis. DESIGN: Retrospective analysis of ED visits in the 1992-2000
      National Hospital Ambulatory Medical Care Survey. Inappropriate medications
      identified using Beers' 1997 explicit criteria. SETTING: EDs of U.S.
      noninstitutionalized general and short-stay hospitals. PARTICIPANTS: ED survey
      patients aged 65 and older. MEASUREMENTS: Magnitude and rate of administration of
      36 medications. RESULTS: Inappropriate medications were administered in an
      estimated 16.1 million (95% confidence interval (CI)=14.9-17.3 million) or 12.6%
      (95% CI=11.6-13.5%) of elderly ED visits from 1992 to 2000. The rate of
      inappropriate administration was unchanged throughout the study period (P=.40).
      Six drugs accounted for 70.8% of inappropriate administration: promethazine
      (22.2%), meperidine (18.0%), propoxyphene (17.2%), hydroxyzine (10.3%),
      diphenhydramine (7.1%), and diazepam (6.0%). In multivariate analysis, number of
      ED medications was the strongest predictor, with an odds ratio for two to three
      medications of 6.0 (95% CI=5.3-6.7) and for four to six medications of 8.1 (95%
      CI=7.2-9.2). Diagnoses indicating potentially appropriate uses of these
      medications were rarely present. For example, only 42.4% of patients receiving
      diphenhydramine and 7.4% receiving hydroxyzine were diagnosed with an allergic
      process. CONCLUSION: Elderly ED patients are frequently administered
      inappropriate medications. Potentially appropriate uses of generally
      inappropriate drugs cannot account for such administrations. Inappropriate
      administration rates remain unchanged despite the 1997 publication of explicit
      criteria.

PMID- 15507062
TI  - Biobehavioral correlates of relocation in the frail elderly: salivary cortisol,
      affect, and cognitive function.
AB  - OBJECTIVES: To examine affect and physiological stress in frail older adults in
      response to a voluntary nursing home relocation. DESIGN: Randomized, controlled
      trial. SETTING: Long-term care facility located within the greater Philadelphia,
      Pennsylvania, community. PARTICIPANTS: Seventy-seven nursing home residents, aged
      65 and over. INTERVENTION: Experimental group residents were relocated to a newly
      built nursing home facility with a cluster design in the fall of 2001; control
      group residents were moved after study completion in the spring of 2002.
      MEASUREMENTS: Mini-Mental State Examination scores, Observed Affect Rating Scale
      scores, salivary cortisol, blood pressure, and pulse obtained 1 week before
      moving and 1 week and 4 weeks after moving. RESULTS: Relocated nursing home
      residents demonstrated significant differences in salivary cortisol and mood from
      a randomly selected group of residents that had not yet moved. Relocation
      resulted in significantly higher cortisol levels 1 week after the move (P=.005),
      followed by a significant decline in afternoon cortisol at 4 weeks after the move
      (P=.03). Moreover, relocated residents had significantly lower depression and
      anxiety symptoms and pulse rates than residents who had not yet moved.
      CONCLUSION: These findings have important implications for planning medical and
      social services for relocated elderly. Efforts should be made to prepare
      individuals for the initial stressors associated with relocation, but it also
      appears that the stress imposed by relocation is time limited and may begin to
      ease as early as 4 weeks postmove.

PMID- 15507063
TI  - Cognitive impairment in chronic kidney disease.
AB  - OBJECTIVES: To assess the prevalence of cognitive impairment in persons with
      chronic kidney disease (CKD) and its relation to the severity of CKD. DESIGN:
      Cross-sectional study. SETTING: University-affiliated ambulatory nephrology and
      dialysis practices. PARTICIPANTS: Eighty subjects with CKD Stages III and IV not
      requiring dialysis (CKD) and 80 subjects with CKD Stage V on hemodialysis (end
      stage renal disease (ESRD)) with a mean age+/-standard deviation of 62.5+/-14.3.
      MEASUREMENTS: Three standardized cognitive tests, the Modified Mini-Mental State
      Examination (3MS), Trailmaking Test B (Trails B), and California Verbal Learning
      Trial (CVLT). Glomerular filtration rate was estimated in subjects with CKD using
      the six-variable Modification of Diet in Renal Disease equation. RESULTS: There
      was a graded relation between cognitive function and severity of CKD. Mean scores
      on the 3MS, Trails B, and CVLT immediate and delayed recall were significantly
      worse for subjects with ESRD than for subjects with CKD or published norms
      (P<.001 for all comparisons). Scores on the Trails B (P<.001) and CVLT immediate
      (P=.01) and delayed (P<.001) recall were significantly worse for subjects with
      CKD not requiring dialysis than for published norms. In addition, the fraction of
      subjects with impairment on the 3MS and Trails B increased with decreasing kidney
      function. CONCLUSION: Cognitive impairment is associated with the severity of
      kidney disease. Further studies are needed to determine the reasons for cognitive
      impairment in subjects with CKD and ESRD.

PMID- 15507064
TI  - Urinary incontinence and psychological distress in community-dwelling older
      African Americans and whites.
AB  - OBJECTIVES: To compare the association between urinary incontinence (UI) and
      psychological distress in older African Americans and whites. DESIGN: A
      population-based longitudinal survey. SETTING: Continuing participants in a study
      of community-dwelling adults who were initially living in East Baltimore in 1981.
      PARTICIPANTS: African Americans and whites aged 50 and older at follow-up
      interviews performed between 1993 and 1996 for whom complete data were available
      (n=747). MEASUREMENTS: Participants were classified as incontinent if any
      uncontrolled urine loss within the 12 months before the interview was reported.
      Psychological distress was assessed using the General Health Questionnaire (GHQ).
      RESULTS: African Americans with UI were more likely to experience psychological
      distress as measured using the GHQ than were African Americans without UI
      (unadjusted odds ratio=4.22, 95% confidence interval=1.72-10.39). In multivariate
      models that controlled for age, sex, education, functional status, cognitive
      status, and chronic medical conditions, this association remained statistically
      significant. The association between UI and psychological distress did not
      achieve statistical significance in whites. CONCLUSION: The effect of UI on
      emotional well-being may be greater for African Americans than for whites.

PMID- 15507065
TI  - Translating research into clinical practice: making change happen.
AB  - OBJECTIVES: To describe the process of adoption of an evidence-based,
      multifaceted, innovative program into the hospital setting, with particular
      attention to issues that promoted or impeded its implementation. This study
      examined common challenges faced by hospitals implementing the Hospital Elder
      Life Program (HELP) and strategies used to address these challenges. DESIGN:
      Qualitative study design based on in-depth, open-ended telephone interviews.
      SETTING: Nine hospitals implementing HELP throughout the United States.
      PARTICIPANTS: Thirty-two key staff members (physician, nursing, volunteer, and
      administrative staff) who were directly involved with the HELP implementation.
      MEASUREMENTS: Staff experiences implementing the program, including challenges
      and strategies they viewed as successful in overcoming challenges of
      implementation. RESULTS: Six common challenges faced hospital staff: (1) gaining
      internal support for the program despite differing requirements and goals of
      administration and clinical staff, (2) ensuring effective clinician leadership,
      (3) integrating with existing geriatric programs, (4) balancing program fidelity
      with hospital-specific circumstances, (5) documenting positive outcomes of the
      program despite limited resources for data collection and analysis, and (6)
      maintaining the momentum of implementation in the face of unrealistic time frames
      and limited resources. Strategies perceived to be successful in addressing each
      challenge are described. CONCLUSION: Translating research into clinical practice
      is challenging for staff across disciplines. Developing strategies to address
      common challenges identified in this study may facilitate the adoption of
      innovative programs within healthcare organizations.

PMID- 15507066
TI  - Safety and immunogenicity of haemophilus influenzae type B polysaccharide or
      conjugate vaccines in an elderly adult population.
AB  - OBJECTIVES: To evaluate the safety and immunogenicity of unconjugated Haemophilus
      influenzae type b (Hib) polysaccharide (PRP) vaccine and two PRP-protein
      conjugated vaccines as a model for the comparison of protein-conjugated versus
      plain polysaccharide vaccines in the elderly. DESIGN: Randomized, double-blind,
      prospective study. SETTING: University-based center for vaccine research and
      development. PARTICIPANTS: A total of 125 adults, aged 64 to 92, who were judged
      to be in general good health and lacking any significant underlying medical
      conditions. INTERVENTION: Subjects were randomized to receive one of three
      vaccines: Group 1 (n=39), PRP; Group 2 (n=44), PRP conjugated to an outer
      membrane protein complex of Neisseria meningitidis (PRP-OMP); and Group 3 (n=42),
      PRP conjugated to diphtheria toxoid (PRP-D). Sera were obtained before
      immunization and 1 and 12 months later. MEASUREMENTS: Subjects maintained a diary
      of injection site and systemic reactions for 3 days after immunization. A
      radioantigen-binding assay was used to measure total concentrations of serum
      anticapsular antibody, and an enzyme-linked immunosorbent assay was used to
      measure immunoglobulin (Ig) G1 and IgG2 anticapsular antibody responses. Antibody
      functional activity was assessed using a complement-mediated bactericidal assay.
      RESULTS: Before vaccination, the geometric mean serum anticapsular antibody
      concentration was 0.8 microg/mL, but fewer than 10% of subjects had detectable
      bactericidal activity (titer>1:4). The magnitude, subclass distribution, and
      bactericidal activity of antibody responses to unconjugated PRP vaccine were
      similar to those observed in previous studies of younger adults immunized with
      PRP. The OMP conjugate, which is highly immunogenic after one dose in 2-month old
      infants, did not elicit anticapsular antibody responses in the elderly greater
      than those elicited by PRP vaccine (P=.43). In contrast, the D conjugate, which
      is poorly immunogenic in 2-month old infants, elicited higher anticapsular
      antibody responses than PRP vaccine in the elderly (P=.01) and higher levels than
      the OMP-conjugate 1 year after vaccination (P<.006). CONCLUSION: Elderly adults
      develop protective anticapsular antibody responses to unconjugated and conjugated
      PRP vaccine. The higher anticapsular antibody responses to the D conjugate but
      not to the OMP conjugate in the elderly, which is the reverse of that observed in
      immunized infants, implies fundamental differences in the immunological
      mechanisms by which the two age groups respond to PRP and by which the OMP and D
      conjugates elicit anticapsular antibody responses.

PMID- 15507068
TI  - Does self-rated health predict survival in older persons with cognitive
      impairment?
AB  - OBJECTIVES: To determine whether baseline self-rated health (SRH) independently
      predicted survival in an older Canadian population and to investigate the role of
      cognition on the SRH-mortality relationship. DESIGN: Population-based prospective
      cohort study. SETTING: Ten Canadian provinces, community-based. PARTICIPANTS: A
      total of 8,697 community-dwelling participants aged 65 and older. MEASUREMENTS:
      Self-reported measures of overall health, physical function, comorbidities, and
      demographic characteristics were obtained by interview. Cognitive ability was
      ascertained using the Modified Mini-Mental State Examination (3MS). Participants
      were followed for their survival status from the initial interview in 1991 until
      October 31, 1996. RESULTS: Subjects with reports of poor SRH were significantly
      more likely to die during follow-up than those reporting good SRH, after
      adjusting for relevant covariates (adjusted hazard ratio (AHR)=1.38, 95%
      confidence interval (CI)=1.24-1.53). SRH was also related to other measures of
      health status across levels of cognitive impairment. SRH remained a significant
      predictor of mortality in subjects with mild to moderate cognitive impairment
      (AHR=1.26, 95% CI=1.01-1.59) but not in those with severe cognitive impairment
      (AHR=1.00, 95% CI=0.76-1.31). CONCLUSION: This study supports the utility of SRH
      assessments in predicting survival of individuals with mild to moderate cognitive
      impairment. The findings highlight the potential role of complex cognitive
      processes underlying the SRH-mortality relationship.

PMID- 15507067
TI  - Inflammatory and thrombotic blood markers and walking-related disability in men
      and women with and without peripheral arterial disease.
AB  - OBJECTIVES: To determine whether higher circulating levels of thrombotic and
      inflammatory markers are associated with greater disability. DESIGN: Cross
      sectional. SETTING: Academic medical center. PARTICIPANTS: A total of 346 men and
      women with peripheral arterial disease (PAD) and 203 without PAD. MEASUREMENTS:
      Disability measures were the Walking Impairment Questionnaire (WIQ) distance,
      speed, and stair-climbing scores and the 36-item Short-Form (SF-36) physical
      functioning score. The SF-36 and WIQ are scored on a 0 to 100 scale (100=best).
      RESULTS: In persons with PAD, higher D-dimer levels were associated with lower
      WIQ speed scores (P<.001), lower stair-climbing scores (P<.04), and poorer SF-36
      physical functioning scores (P<.01), adjusting for known and potential
      confounders. In participants without PAD, higher D-dimer levels were associated
      with lower WIQ distance scores (P<.03), lower speed scores (P<.05), and poorer SF
      36 physical functioning scores (P<.02). Higher high-sensitivity C-reactive
      protein (hsCRP) levels were associated with lower WIQ distance (P<.02) and speed
      scores (P<.001) in persons without PAD. Most of these associations were
      attenuated after additional adjustment for objectively measured functional
      limitations. CONCLUSION: Higher circulating D-dimer and hsCRP levels are
      associated with greater disability in walking and physical functioning in
      individuals with and without PAD. Physiological changes that result in walking
      disability may mediate these associations.

PMID- 15507069
TI  - Association between visual attention and mobility in older adults.
AB  - OBJECTIVES: To examine the association between visual attention/processing speed
      and mobility in older adults. DESIGN: Cross-sectional. SETTING: Clinical research
      unit of a department of ophthalmology. PARTICIPANTS: Three hundred forty-two
      older adults (aged 55-85) living independently in the community recruited from
      primary eye care practices. MEASUREMENTS: In addition to demographic, health, and
      functional information, the following variables were collected at the second
      annual visit of a prospective study on mobility: a test of visual
      attention/processing speed; a performance mobility assessment; and self-reported
      measures of falls, falls efficacy, mobility/balance, and physical activity.
      RESULTS: Lower scores on visual attention/processing speed were significantly
      related to poorer scores on the performance mobility assessment, even after
      adjustment for age, sex, race, education, number of chronic medical conditions,
      cognitive status, depressive symptoms, visual acuity, and contrast sensitivity
      (P=.04). Scores on the visual attention/processing speed test were unrelated to
      the self-reported measures of mobility. CONCLUSION: Results imply that visual
      attention impairment/slowed visual processing speed in older adults is
      independently associated with mobility problems. Interventions to reverse or
      minimize the progression of mobility dysfunction in older adults should take this
      common aging-related deficit in visual processing into account.

PMID- 15507070
TI  - The coming epidemic of obesity in elderly Americans.
AB  - OBJECTIVES: To estimate the prevalence of obesity in elderly Americans in 2010
      and to discuss the health and economic implications of these estimates. DESIGN:
      Three methods of generating future point-prevalence estimates using data from
      consecutive cross-sectional studies. SETTING: All regions of the United States.
      PARTICIPANTS: Estimates were based on five nationally representative surveys of
      the adult population of the United States, conducted from 1960 to 2000, and
      population estimates from the U.S. Census Bureau. MEASUREMENTS: Changes in
      obesity (body mass index (BMI) > or =30 kg/m(2)) and normal weight (BMI <25
      kg/m(2)) prevalence for men and women by 10-year U.S. birth cohorts were
      examined. The prevalence of obesity and normal weight in the elderly in 2010 was
      estimated under three different scenarios of obesity prevalence change. RESULTS:
      It was estimated that the prevalence of obesity in adults aged 60 and older will
      increase from 32.0% in 2000 to 37.4% in 2010 (range 33.6-39.6%). The number of
      obese adults aged 60 and older will increase from 14.6 to 20.9 million (range
      18.8-22.2 million). Similarly, it was estimated that the prevalence of normal
      weight among adults aged 60 and older will decrease from 30.6% in 2000 to 26.7%
      in 2010 (range 31.0-24.7%). CONCLUSION: The prevalence of obesity in elderly
      Americans will likely continue to increase, challenging healthcare delivery and
      financing systems in the United States.

PMID- 15507071
TI  - Unprovoked and glyceryl trinitrate-provoked head-up tilt table test is safe in
      older people: a review of 10 years' experience.
AB  - OBJECTIVES: To test the safety of the head-up tilt test (HUT) in older adults.
      DESIGN: Direct observation and measurements. SETTING: Tests performed in a quiet
      room with dim lighting in a laboratory setting. PARTICIPANTS: One thousand ninety
      six subjects aged 60 to 74; 873 aged 75 and older. MEASUREMENTS: Blood pressure
      and pulse at baseline for 10 minutes and 70 degrees tilt for maximum of 45
      minutes. Subjects with unprovoked HUT had test repeated on a separate day after
      800 mg glyceryl trinitrate (GTN). RESULTS: One thousand four hundred ninety-five
      drug-free and 474 GTN-provoked HUTs were studied. In those aged 60 to 74, the
      proportion of hypotensive unprovoked HUT was 16% (27% in those aged > or =75);
      this was higher with GTN provocation (43% in those aged 60-74, 44% in those aged
      > or =75; P<.01). Systolic blood pressure decreased during provoked HUT (lowest
      mean+/-standard deviation=67+/-20 in those aged 60-74, 63+/-24 in those aged > or
      =75; P<.01). There was one cardiovascular and no neurological complications.
      CONCLUSION: This study included 10 times as many people as previous studies and
      demonstrates the safety of HUT in older people.

PMID- 15507072
TI  - Pharmacotherapy of pain in depressed older adults.
AB  - OBJECTIVES: To examine pharmacotherapy for pain in a sample of 1,801 depressed
      older primary care patients. DESIGN: Cross-sectional survey data collected from
      1999 to 2001. SETTING: Eighteen primary care clinics belonging to eight
      healthcare organizations in five states. PARTICIPANTS: One thousand eight hundred
      one patients aged 60 and older who met diagnostic criteria for major depression
      or dysthymia. MEASUREMENTS: Diagnoses or treatment for chronic pain, functional
      impairment from pain, and use of over-the-counter and prescription analgesic
      medications. RESULTS: One thousand four hundred sixteen (79%) participants
      reported functional impairment from pain in the previous month, and 1,024 (57%)
      reported a diagnosis of or treatment for chronic pain in the previous 3 years.
      Fifty-one percent of those with recent functional impairment from pain reported
      any analgesic use, ranging from 31% to 75% across the participating healthcare
      organizations. Opioid analgesic use varied from 5% to 34%. Predictors of
      analgesic use included a history of chronic pain or arthritis and the degree of
      functional impairment from pain in the previous month. Differences in analgesic
      use across participating organizations remained significant after adjusting for
      clinical and demographic covariates. CONCLUSION: Most depressed older adults in
      the sample reported recent functional impairment from pain and a history of
      chronic pain, but almost half of those with functional impairment from pain did
      not report using analgesic medications. Participating organizations varied
      substantially in their use of analgesics, suggesting that there is room to
      improve the quality of pain management in depressed older adults.

PMID- 15507073
TI  - How should clinicians describe hospice to patients and families?
AB  - OBJECTIVES: To describe hospice enrollment from the perspective of bereaved
      family members and to identify information about hospice that would encourage
      patients and families to enroll sooner. DESIGN: Cross-sectional interviews.
      SETTING: Three Medicare-certified hospice organizations. PARTICIPANTS: One
      hundred family members of 100 patients who died in hospice. MEASUREMENTS:
      Semistructured interviews assessed prior knowledge of hospice, patients' and
      physicians' involvement in the enrollment process, features of hospice that
      motivated enrollment, and features that patients and families wished they had
      learned about sooner. RESULTS: Almost all family members (n=92) and patients
      (n=71) knew about hospice before the patient's illness. Almost half the patients
      (n=44) were not involved at all in the hospice enrollment decision. The patient's
      physician (n=51) or the patient or family (n=34) initiated most hospice
      discussions, but patients and families usually obtained information about hospice
      from a hospice representative (n=75) rather than from the patient's physician
      (n=22). Family members identified several kinds of information about hospice that
      were particularly helpful in deciding whether to enroll and described several
      aspects of hospice that they wished they had known about sooner. CONCLUSION: Many
      patients and families learn about hospice from someone other than the patient's
      physician, and most learn about valuable hospice features and services only after
      enrollment. By providing more information about hospice earlier in the illness
      course, clinicians may be able to facilitate more-informed and more-timely
      decisions about hospice enrollment.

PMID- 15507074
TI  - Operationalizing a frailty index from a standardized comprehensive geriatric
      assessment.
AB  - OBJECTIVES: To construct and validate a frailty index (FI) that is clinically
      sensible and practical for geriatricians by basing it on a routinely used
      comprehensive geriatric assessment (CGA) instrument. DESIGN: Secondary analysis
      of a 3-month randomized, controlled trial of a specialized mobile geriatric
      assessment team. SETTING: Rural Nova Scotia. Participants were seen in their
      homes. PARTICIPANTS: Frail older adults, of whom 92 were in the intervention
      group and 77 in the control group. MEASUREMENTS: A standard CGA form that
      accounts for impairment, disability, and comorbidity burden was scored and summed
      as a frailty index (FI-CGA). The FI-GCA was stratified to describe three levels
      of frailty. Patients were followed for up to 12 months to determine how well the
      index predicted adverse outcomes (institutionalization or mortality, whichever
      came first). RESULTS: The three levels of frailty were mild (FI-CGA 0-7),
      moderate (FI-CGA 7-13), and severe (FI-CGA>13). Demographic and social traits
      were similar across groups, but greater frailty was associated with worse
      function (r=0.55) and mental status (r=0.33). Those with moderate and severe
      frailty had a greater risk of adverse outcomes than those with mild frailty
      (unadjusted hazard ratio=1.9 and 5.5, respectively). There was no difference
      between frailty groups in mean 3-month goal-attainment scaling scores. Intrarater
      reliability was 0.95. CONCLUSION: The FI-CGA is a valid, reliable, and sensible
      clinical measure of frailty that permits risk stratification of future adverse
      outcomes.

PMID- 15507075
TI  - Inappropriate medication use and health outcomes in the elderly.
AB  - Inappropriate medication use is a major problem for the elderly. Although
      increasing attention has been paid to inappropriate prescription medication use,
      most previous research has been limited to the investigation of prevalence and
      trends. Few studies provide the empirical evidence for the adverse effect of
      inappropriate medication use on health outcomes at the national level. This study
      is the first attempt to assess the relationship between inappropriate
      prescription use and health status for the elderly in the United States. Based on
      the 1996 Medical Expenditure Panel Survey, inappropriate medication use in a
      national representative elderly population was first identified using Beers
      criteria. A survey type of ordered probit model was then estimated to quantify
      the effect of inappropriate drug use on patient self-perceived health status
      measured using a five-point scale (poor, fair, good, very good, and excellent).
      After controlling for a set of possible confounding factors, it was found that
      individuals using inappropriate medications in Round 1 were more likely than
      those not using inappropriate medications to report poorer health status in Round
      2. Other risk factors for poor health status include a higher number of
      prescriptions, being black, having low education, and having one or more chronic
      diseases. This study provides strong evidence of a significant adverse effect of
      inappropriate medication use on patient health status. These findings lend
      partial support to the use of Beers criteria in assessing the quality of
      prescribing and the appropriateness of medication use in the elderly population.

PMID- 15507076
TI  - Return on educational investment in geriatrics training.
AB  - The graying of America will increase demand for specialists in geriatric
      medicine, but the proportion of filled fellowship positions in geriatric medicine
      has been falling recently. The objective of this study was to examine the
      financial return of additional training in geriatric medicine for general
      internists by using survey data from the American Medical Association and
      standard financial techniques. The return on educational investment over a
      working lifetime for a third-year resident in internal medicine who was
      considering specialty training in geriatric medicine between 1993 and 1999 was
      calculated. Physicians self-identified as geriatricians had lower incomes and
      lower incomes per hour than age-matched general internists, although the
      disparities decreased somewhat over the period examined. Regression modeling
      suggested that incomes for geriatricians are lower than expected and that this
      disparity increased in the last 2 years of the study. Some of the income
      disparities may be attributable to the fact that geriatricians obtain a greater
      proportion of their total revenue from Medicare than is optimal in the generalist
      setting. Returns on educational investment for geriatrics training were negative,
      although less so in recent years. Analysis suggests that the pursuit of
      additional specialty training in geriatric medicine has a negative financial
      return. Financial returns and the incentives they create should be carefully
      considered in meeting the anticipated geriatrics workforce needs of the nation.

PMID- 15507078
TI  - Cruise ship care: a proposed alternative to assisted living facilities.
AB  - Options for elderly patients who can no longer remain independent are limited.
      Most choices involve assisted living facilities, 24-hour caregivers, or nursing
      homes. State and federal assistance for payment for individual care is limited,
      and seniors usually pay for most costs out of pocket. For those patients who have
      the means to afford assisted living centers or nursing homes, "cruise ship care"
      is proposed. Traveling alongside traditional tourists, groups of seniors would
      live on cruise ships for extended periods of time. Cruise ships are similar to
      assisted living centers in the amenities provided, costs per month, and many
      other areas. This article begins with an examination of the needs of seniors in
      assisted living facilities and then explores the feasibility of cruise ship care
      in answering those needs. Similarities between cruise ship travel and assisted
      living care, as well as the monetary costs of both options, are defined. A
      decision tree with selections for non-independent care for seniors was created
      including cruise ship care as an alternative. Using a Markov model over 20 years,
      a representative cost-effectiveness analysis was performed that showed that
      cruises were priced similarly to assisted living centers and were more
      efficacious. Proposed ways that cruise ship companies could further accommodate
      the needs of seniors interested in this option are also suggested. Implementation
      for cruise ship care on the individual basis is also presented. Ultimately, it is
      wished to introduce a feasible and possibly more desirable option to seniors who
      can no longer remain independent.

PMID- 15507077
TI  - Time since immigration and health services utilization of Korean-American older
      adults living in Los Angeles County.
AB  - The aim of this study was to characterize ambulatory healthcare utilization of
      older Korean Americans and its association with length of time since immigration.
      It was hypothesized that older Korean Americans who were recent immigrants would
      use outpatient physician visits less often than early immigrants. The data are
      from the 2000 Korean-American Health Survey, which assessed the health status and
      medical needs of Korean Americans living in Los Angeles County. The dependent
      variable was the number of visits to a physician for check-up or consultation.
      Multivariate regression modeling was used to assess the influence of length of
      time since immigration on the dependent variable controlling for predisposing,
      enabling, and need variables for a sample of 208 Koreans Americans aged 65 and
      older. Results indicated that high school education in Korea and health insurance
      status were significant predictors of number of visits to a physician during the
      previous year (P<.05). The main variable of interest, the number of years living
      in the United States, approached significance at P=.09. It was concluded that
      enabling variables such as education and health insurance significantly
      influenced use of healthcare services in the older Korean-American population.
      The lack of studies regarding older minority populations and their access to
      healthcare further highlight theneed not only to characterize the access of these
      often-vulnerable populations, but also to generate interest for further studies.

PMID- 15507079
TI  - Relationship between homocysteine and cardiovascular diseases in older adults.

PMID- 15507080
TI  - The bath! Reassessing a familiar elixir in old age.

PMID- 15507081
TI  - Physician recruitment into geriatrics--further insight into the black box.

PMID- 15507082
TI  - Insulin-like growth factor-1.

PMID- 15507083
TI  - Tiredness and onset of walking limitations in older adults.

PMID- 15507084
TI  - Silent colo-uterine fistula in an elderly woman.

PMID- 15507085
TI  - Switching from donepezil or rivastigmine to galantamine in clinical practice.

PMID- 15507086
TI  - Ileo-ceco-colic intussusception in a 92-year-old man.

PMID- 15507087
TI  - Anticoagulation to prevent strokes in older people with atrial fibrillation:
      assembling individualized risk and benefit information.

PMID- 15507088
TI  - Long term tracking of methicillin-resistant Staphylococcus aureus in a large
      skilled nursing facility.

PMID- 15507089
TI  - Reduction of falls-related injuries using a hospital inpatient falls prevention
      program.

PMID- 15507091
TI  - Chemokine receptor antagonists: a novel therapeutic approach in allergic
      diseases.
AB  - The aim of this review is to give an overview of the role of chemokines,
      particularly ligands of the CC chemokine receptor CCR3, in allergic diseases and
      to show the new concept in the treatment of allergies using chemokine receptor
      antagonists. Allergic diseases such as allergic asthma, allergic rhinitis and
      atopic dermatitis are characterized by a complex interaction of different cell
      types and mediators. Among this, Th2 cells, mast cells, basophils and eosinophils
      are found in the inflamed tissue due to the attraction of chemokines. Of all the
      known chemokine receptors, the chemokine receptor CCR3 seems to play the major
      role in allergic diseases which is supported by the detection of this receptor on
      the cell types mentioned above. Therefore, academic and industrial research focus
      on compounds to block this receptor. To date, certain chemokine receptor
      antagonists derived from peptides and small molecules exist to block the
      chemokine receptor CCR3. However, the in vivo data about these compounds and the
      mechanisms of receptor interaction are poorly understood, as yet. For the
      development of additional chemokine receptor antagonists, more details about the
      interaction between the ligands and their receptors are required. Therefore,
      additional studies will lead to the identification of novel CCR3 chemokine
      receptor antagonists, which can be therapeutically used in allergic asthma,
      allergic rhinitis, and atopic dermatitis.

PMID- 15507092
TI  - EU regulation: what's new in terms of labelling of food allergens?

PMID- 15507093
TI  - Information provision for allergic consumers--where are we going with food
      allergen labelling?
AB  - As the current treatment for food allergy involves dietary exclusion of the
      problem food, information for food-allergic consumers provided on food labels
      about the nature of allergenic ingredients is important to the management of
      their condition. The members of an EU-funded networking project, InformAll,
      focusing on developing strategies for the provision of credible, reliable sources
      of information for food allergy sufferers, regulators and the food industry, have
      been considering these matters with respect to food labelling. This paper
      presents an overview of the genesis of the new EU directive on food labelling,
      its relevance to food-allergic consumers and the problems that might arise if
      precautionary labelling becomes more widespread in response to concerns regarding
      inadvertent allergen contamination in foods. International efforts to define
      threshold levels of allergens able to trigger a reaction coupled with validated
      allergen detection methods are essential if the food industry is to implement
      effective hazard control procedures and address the problems of cross-contact
      allergens without devaluing the information provided to consumers on food labels.

PMID- 15507094
TI  - Effects of birch pollen SIT on apple allergy: a matter of dosage?

PMID- 15507095
TI  - Effect of tree pollen specific, subcutaneous immunotherapy on the oral allergy
      syndrome to apple and hazelnut.
AB  - BACKGROUND: The efficacy of specific immunotherapy (SIT) in pollen allergy is
      well established. However, its effect on pollen associated food allergy
      particularly the oral allergy syndrome (OAS) is not definitely ascertained.
      OBJECTIVE: The purpose of this controlled prospective study was to investigate
      whether SIT with tree pollen, mainly birch, has an effect on OAS induced by apple
      or hazelnut in birch pollen-allergic individuals. METHODS: Twenty-seven birch
      pollen-allergic subjects with OAS induced by apple or hazelnut underwent open
      oral provocation tests (OPT) with increasing doses (1 to 128 g) of fresh apple or
      ground hazelnut 1 year apart. Fifteen of 27 subjects were treated with SIT and 12
      were not. Skin-prick test with birch pollen, apple and hazelnut, and specific
      serum IgE, IgG and IgG4 to rBet v 1, apple and hazelnut were determined. RESULTS:
      Thirteen of 15 (87%) SIT-treated subjects could eat significantly (P <0.001) more
      of apple or hazelnut without any symptoms/signs. The average tolerated quantity
      increased from 12.6 to 32.6 g apple after 1 year in this group. In contrast, only
      one of 12 (8%) individuals without SIT was able to consume a higher amount
      without symptoms. On evaluating laboratory parameters, only IgG4 antibodies to
      rBet v 1 were found to be significantly (P <0.01) increased in the SIT-treated
      group after 1 year. CONCLUSIONS: The study shows that SIT with extracts
      containing birch pollen has a positive impact on OAS to apple or hazelnut in
      birch pollen-allergic individuals. In spite of this outcome, the amount of
      apple/hazelnut tolerated is still small. Thus, the effect of SIT on the patients'
      management of OAS remains limited.

PMID- 15507096
TI  - Bet v 1 homologues in strawberry identified as IgE-binding proteins and
      presumptive allergens.
AB  - BACKGROUND: No strawberry allergen has so far been identified and characterized.
      METHODS: Serum samples were collected from patients with a suggestive case
      history of adverse reactions to strawberry and other fruits. Extracts from fresh
      and frozen strawberries were analysed by sodium dodecyl sulphate-polyacrylamide
      gel electrophoresis (SDS-PAGE), Western blotting and mass spectrometry. Patient
      blood samples were analysed for inhibition of IgE binding and basophil
      degranulation. RESULTS: Several IgE-binding proteins could be detected. In more
      than half of the patient sera, a 20/18-kDa doublet band was observed in Western
      blotting. These two bands were excised and analysed by mass spectrometry showing
      the presence of proteins belonging to the Bet v 1 family of allergens. Inhibition
      of the IgE binding to the 20/18-kDa doublet was obtained by addition of two
      recombinantly expressed allergens belonging to the Bet v 1 family (Bet v 1 and
      Mal d 1) and strawberry protein extract. In a cell-based assay of patient blood
      samples, basophil degranulation could be induced by strawberry protein extract
      and by Bet v 1 and Mal d 1. CONCLUSIONS: We conclude that strawberry homologues
      to Bet v 1 may be allergens of importance for adverse reactions to strawberry.

PMID- 15507097
TI  - A prospective, randomized, double-blind, placebo-controlled multi-centre study on
      the efficacy and safety of sublingual immunotherapy (SLIT) in children with
      seasonal allergic rhinoconjunctivitis to grass pollen.
AB  - BACKGROUND: Especially in childhood, sublingual immunotherapy (SLIT) could offer
      advantages over subcutaneous therapy. However, limited data on its efficacy is
      available. METHODS: In four German centres 97 children (age 3-14 years) with
      allergic rhinoconjunctivitis to grass pollen were enrolled in a prospective,
      double-blind trial comparing SLIT (Pangramin SLIT; ALK-SCHERAX, 0.5 microg major
      allergens, three times per week, 32 months) with placebo. Primary endpoint was a
      multiple symptom-medication score for changes in seasonal diary entries between
      the first and third year of the study (SLIT n=39; placebo n=38). RESULTS: The
      multiple symptom-medication score was significantly reduced by SLIT to 77.3% of
      the placebo group (P=0.0498). The subsequent analysis of the single endpoints did
      not reveal significant differences for symptom scores in favour of SLIT (85.1% of
      placebo group; P=0.22). However, the medication score improved significantly
      (67.1% of placebo group; P=0.0025). Furthermore, secondary endpoints assessing in
      vivo immune responses did not differ significantly between the groups. However,
      retrospective analysis showed some inhomogeneity for clinical and in vitro
      parameters at the beginning of the study. Allergic side effects with possible
      relation to the study drug were reported in both groups (SLIT 49%, placebo 27%,
      P=0.026). CONCLUSION: Our study indicates that SLIT had a positive effect on the
      reduction of a multiple symptom-medication score, mainly by significantly
      reducing rescue medication use, but had no significant effect on symptoms alone
      in children with rhinoconjunctivitis to grass pollen compared with a placebo.

PMID- 15507098
TI  - Small nonspecialized farming as a protective factor against immediate-type
      occupational respiratory allergy?
AB  - BACKGROUND: In Poland small, nonspecialized farms, growing different crops and
      raising usually a few animals of various species constitute the majority.
      OBJECTIVE: The aim of the case-control study was to evaluate the risk factors of
      work-related respiratory symptoms and occupational asthma and/or rhinitis in
      Polish farmers and investigate whether the farming characteristics may have
      influence on the prevalence of atopy and allergic diseases. METHODS: The study
      groups comprised 100 cases who were farmers reporting work-related asthmatic
      and/or rhinitis symptoms from randomly selected family doctors practices (80 of
      353) and 102 healthy controls. All subjects were examined by means of a
      questionnaire, skin prick tests (SPT) to common and occupational allergens, total
      serum immunoglobulin (Ig)E level and the presence of specific IgE and allergen
      specific inhalation challenge tests were performed. The provocation tests were
      monitored with the spirometry, histamine challenge test and evaluation of nasal
      symptoms score and nasal washings. RESULTS: Respiratory allergic disease was
      recognized in 68 symptomatic patients, including 41 cases because of occupational
      allergens (asthma n=38, rhinitis n=41). Step-wise logistic regression analysis
      confirmed the protective role of small farms against the development of work
      related symptoms (OR 0.23; 95% CI 0.11, 0.47) as well as the significance of
      positive SPT to cereals (OR 5.55; 95% CI 1.6, 19.21) and storage mites (OR 3.73;
      95% CI 1.27, 10.96) as a risk factor of these symptoms. Cereal farming (OR 13.75;
      95% CI 2.39, 78.83) and positive SPT to cereals (OR 26.92; 95% CI 5.33, 135.9)
      and storage mites (OR 44.07; 95% CI 8.40, 231.1) were found to be significant
      risk factors of occupational asthma and/or rhinitis. CONCLUSIONS: Cereal farming
      and hypersensitivity to cereals plays the significant role in the development of
      occupational asthma among Polish farmers. It also seems that working on small
      farms may protect farmers against work-related respiratory symptoms that are
      mostly because of allergy.

PMID- 15507099
TI  - Stabilization of asthma prevalence among adolescents and increase among
      schoolchildren (ISAAC phases I and III) in Spain.
AB  - BACKGROUND: Most studies show a steep increase in asthma prevalence in the last
      decades, although few studies had applied the same methodology. Recent reports
      point out the possibility that the epidemic has come to an end. We have studied
      the prevalence of asthma in a very large sample of children, repeating the study
      eight years apart. METHODS: Repeated cross-sectional studies using the
      International Study of Asthma and Allergies in Childhood (ISAAC) protocol in a
      sample of Spanish schoolchildren 6-7 (parent-reported) and 13-14 (self-reported)
      years old in 1994-95 (phase I) and 2002-2003 (phase III). The number of
      participants was 42 417 in phase I and 42 813 in phase III. The participation
      rate was over 87% (13-14 years) and 70% (6-7 years). RESULTS: The prevalence of
      wheezing in the previous year in children aged 13-14 years was 9.0 and 9.3% for
      boys and 9.6 and 9.2% for girls for phases I and III, respectively. Children 6-7
      years of age showed a substantial increase in wheezing in the previous year (7.0
      and 10.7% for boys and 5.3 and 8.2% for girls). Other symptoms and severity
      indexes followed the same patterns. CONCLUSIONS: In the last 8 years, the
      prevalence of asthma has not changed in 13-14-year-old Spanish children but has
      increased substantially in 6-7-year olds.

PMID- 15507100
TI  - Increased allergen concentration enhances IFN-gamma production by allergic donor
      T cells expressing a peripheral tissue trafficking phenotype.
AB  - BACKGROUND: Clinically effective allergen-specific immunotherapy correlates with
      decreased circulating allergen-specific IL-4+ T cells but increased IFN-gamma+
      cells at sites of allergen challenge. Whether immunotherapy promotes trafficking
      of IFN-gamma+ T cells to peripheral tissues is unknown. As aeroallergen is
      administered at higher concentrations during immunotherapy than those encountered
      naturally, the effect of allergen concentration on adhesion molecule (CD62L and
      CD49d) and chemokine receptor (CCR3 and CCR5) expression by peripheral-blood T
      cells was analysed in parallel with cytokine production. METHODS: House dust mite
      allergic donor peripheral blood mononuclear cells were cultured for 14 days with
      different allergen concentrations. Cytokine profiles of were analysed by flow
      cytometry. RESULTS: Cultures stimulated with 100 microg/ml house dust mite
      extract compared with 1 microg/ml had increased proportions and numbers of
      CD62Llo, CD49dhi or CCR5+ T cells expressing IFN-gamma. CCR3-positive CD4+ and
      CD8+ T cell numbers were very low and did not differ between cultures. In
      contrast the proportions of 'peripheral tissue trafficking' CD4+ T cells
      expressing IL-4 were decreased in cultures stimulated with high in comparison
      with low allergen concentration. CONCLUSION: These results indicate the
      importance of achieving high allergen doses during immunotherapy to promote IFN
      gamma production and expression of a 'peripheral tissue trafficking' phenotype by
      allergen-specific CD4+ and CD8+ T cells. The net change in cytokine milieu at
      sites of allergen encounter would then down-regulate clinical manifestations of
      allergic disease.

PMID- 15507102
TI  - Specific serum IgE levels and FcepsilonRIbeta genetic polymorphism in patients
      with penicillins allergy.
AB  - BACKGROUND: Numerous studies have suggested that both genetic and environmental
      influences are involved in the pathogenesis of allergic disease and atopy. The
      objective of this investigation is to elucidate the underlying mechanism of
      penicillins allergy and improve the diagnostic methods. METHODS:
      Radioallergosorbent test was used to examine eight kinds of specific IgE
      antibodies, which included four kinds of major and minor antigenic determinants,
      respectively, in the sera of 448 patients with penicillins allergy and 101
      healthy subjects. A restriction endonuclease fragment length polymorphism of a
      polymerase chain reaction product was used for analysis of the FcepsilonRIbeta
      polymorphism. RESULTS: The positive rate of specific IgE in 448 patients was
      58.26% (261), in which 37.28% (167) patients had positive IgE to major antigenic
      determinants and 47.09% (211) patients had positive IgE to minor antigenic
      determinants. Of the 179 patients with allergic history, 70.83% (17/24) patients
      had positive antibodies within 30 days, while 45.28% (24/53) had positive
      antibodies after 5 years. The positive reaction degree of skin test was
      absolutely correlated with specific IgE (P=0.047). Among patients with positive
      specific IgE, significant differences of E237G genotype were observed between
      patients with positive benzylpenicillanyl (BPA)-, phenoxomethylpenicilloyl (PVO)-
      or ampicilloyl (APO)-IgE and control group (P=0.015, 0.015, and 0.008,
      respectively). There were significant differences in E237G genotype between
      positive and negative BPA-, PVO- as well as APO-IgE patients (P = 0.014, 0.02,
      and 0.011, respectively). CONCLUSIONS: The patients with penicillins allergy have
      positive specific IgE not only to major antigenic determinants but also to minor
      antigenic determinants. The E237G variant of the FcepsilonRIbeta gene is involved
      in the development of penicillins allergy through the process for the production
      of specific IgE antibodies.

PMID- 15507101
TI  - The prevalence of positive reactions in the atopy patch test with aeroallergens
      and food allergens in subjects with atopic eczema: a European multicenter study.
AB  - BACKGROUND: The atopy patch test (APT) was proposed to evaluate IgE-mediated
      sensitizations in patients with atopic eczema (AE). OBJECTIVE: The prevalence and
      agreement with clinical history and specific IgE (sIgE) of positive APT reactions
      was investigated in six European countries using a standardized method. METHODS:
      A total of 314 patients with AE in remission were tested in 12 study centers on
      clinically uninvolved, non-abraded back skin with 200 index of reactivity (IR)/g
      of house dust mite Dermatophagoides pteronyssinus, cat dander, grass, and birch
      pollen allergen extracts with defined major allergen contents in petrolatum.
      Extracts of egg white, celery and wheat flour with defined protein content were
      also patch tested. APT values were evaluated at 24, 48, and 72 h according to the
      European Task Force on Atopic Dermatitis (ETFAD) guidelines. In addition, skin
      prick test (SPT) and sIgE and a detailed history on allergen-induced eczema
      flares were obtained. RESULTS: Previous eczema flares, after contact with
      specific allergens, were reported in 1% (celery) to 34% (D. pteronyssinus) of
      patients. The frequency of clear-cut positive APT reactions ranged from 39% with
      D. pteronyssinus to 9% with celery. All ETFAD intensities occured after 48 and 72
      h. Positive SPT (16-57%) and elevated sIgE (19-59%) results were more frequent.
      Clear-cut positive APT with all SPT and sIgE testing negative was seen in 7% of
      the patients, whereas a positive APT without SPT or sIgE for the respective
      allergen was seen in 17% of the patients. APT, SPT and sIgE results showed
      significant agreement with history for grass pollen and egg white (two-sided Pr >
      /Z/ < or = 0.01). In addition, SPT and sIgE showed significant agreement with
      history for the other aeroallergens. With regard to clinical history, the APT had
      a higher specificity (64-91% depending on the allergen) than SPT (50-85%) or sIgE
      (52-85%). Positive APT were associated with longer duration of eczema flares and
      showed regional differences. In 10 non-atopic controls, no positive APT reaction
      was seen. CONCLUSION: Aeroallergens and food allergens are able to elicit
      eczematous skin reactions after epicutaneous application. As no gold standard for
      aeroallergen provocation in AE exists, the relevance of aeroallergens for AE
      flares may be evaluated by APT in addition to SPT and sIgE. The data may
      contribute to the international standardization of the APT.

PMID- 15507103
TI  - Allergy and Pediatric Allergy and Immunology are the official organs of the
      European Academy of Allergology and Clinical Immunology.

PMID- 15507105
TI  - Androgen action on human skin -- from basic research to clinical significance.
AB  - Androgens affect several functions of the human skin, such as sebaceous gland
      growth and differentiation, hair growth, epidermal barrier homeostasis and wound
      healing. Their effects are mediated by binding to nuclear androgen receptors.
      Androgen activation and deactivation are mainly intracellular events. They differ
      from cell type to cell type and between cells at different locations. The major
      circulating androgens, dehydroepiandrosterone sulfate and androstenedione, are
      predominantly produced in the adrenal glands, and testosterone and 5alpha
      dihydrotestosterone are mainly synthesized in the gonads. Testosterone in women
      and 5alpha-dihydrotestosterone in both genders are also synthesized in the skin.
      Skin cells express all androgen metabolizing enzymes required for the independent
      cutaneous synthesis of androgens and the development of hyperandrogenism
      associated conditions and diseases, such as seborrhea, acne, hirsutism and
      androgenetic alopecia. The major thrust of drug design for the treatment of
      androgen-associated disorders has been directed against several levels of
      androgen function and metabolism. Partial effectiveness has only been achieved
      either by androgen depletion, inhibition of androgen metabolism or blockade of
      the androgen receptor.

PMID- 15507106
TI  - Vitamin D and skin: new aspects for dermatology.
AB  - It has been shown that epidermal keratinocytes have the capacity for the UVB
      induced photochemical conversion of 7-dehydrocholesterol to vitamin D3, and also
      for the enzymatically controlled hydroxylation of the photolysis product. This
      metabolic loop results in the formation of the biologically active final product
      1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3, calcitriol). The epidermal
      synthesis of calcitriol is of fundamental relevance because calcitriol regulates
      important cellular functions in keratinocytes and immunocompetent cells. Because
      of their anti-proliferative and prodifferentiating effects, calcitriol and other
      vitamin D analogs are highly efficient in the treatment of psoriasis vulgaris. In
      addition, the known therapeutic effect of UVB light therapy in the treatment of
      psoriasis may, at least in part, be mediated via UVB-induced synthesis of
      calcitriol. Increasing evidence now indicates that cutaneous vitamin D synthesis
      is of great importance for the prevention of a broad variety of diseases,
      including various malignancies. It has been postulated that cancer mortality
      could be reduced via careful UV exposure or, more safely, via oral substitution
      with vitamin D. These new findings must be taken into account when establishing
      new sun protection guidelines for the prevention of skin cancer. In addition,
      better understanding of the metabolism of vitamin D in the skin has opened up new
      perspectives for the therapeutic application of vitamin D analogs, e.g. in
      inflammatory skin diseases.

PMID- 15507107
TI  - Melanocortins in fibroblast biology--current update and future perspective for
      dermatology.
AB  - The skin is a target organ and source for proopiomelanocortin (POMC)-derived
      peptides, such as alpha-melanocyte-stimulating hormone (alpha-MSH), which acts by
      binding to melanocortin receptors (MC-Rs). Recent progress in our understanding
      of the cutaneous POMC system has demonstrated that human dermal fibroblasts
      (HDFs) are a novel target for alpha-MSH. MC-1R is expressed by HDFs in vitro and
      in situ. MC-1R expression is also detectable in human connective tissue sheath
      fibroblasts (CTSFs) and in dermal papilla cells (DPCs) of the hair follicle, the
      latter concomitantly expressing MC-1R and MC-4R in vitro and in situ. Both HDFs
      and DPCs are capable of generating POMC-derived peptides, although cell-specific
      differences exist in the expression of prohormone convertases and the amounts of
      POMC-derived peptides generated. Functional studies have shown that alpha-MSH
      exerts anti-inflammatory actions in human fibroblastic skin cells by suppressing
      interleukin-1 (IL-1)-induced IL-8 production, activation of the transcription
      factor activator protein-1 (AP-1) and induction of intercellular adhesion
      molecule-1 by interferon-alpha. In addition, alpha-MSH antagonizes the effect of
      transforming growth factor-beta1 (TGF-beta1) on collagen synthesis in HDFs in
      vitro and exerts antifibrogenic activity in a mouse model of cutaneous fibrosis.
      These findings indicate that fibroblastic cells participate in the cutaneous POMC
      system in which alpha-MSH appears to act as a modulator of inflammatory and
      fibrogenic responses. The biological activities of alpha-MSH in fibroblastic
      cells of the skin point towards novel clues in our understanding of the
      pathophysiology of fibrotic skin disorders and inflammatory diseases of the hair
      follicle and, finally, suggest innovative therapeutic options for the treatment
      of these conditions.

PMID- 15507108
TI  - Neutral endopeptidase and angiotensin-converting enzyme -- key enzymes
      terminating the action of neuroendocrine mediators.
AB  - Zinc-metalloproteases, such as neutral endopeptidase (NEP) and angiotensin
      converting enzyme (ACE), effectively control the bioavailability of peptide
      mediators released from sensory nerves, immune and skin cells during the
      cutaneous response to endogenous or exogenous noxious stimuli. Functional
      inactivation of NEP or ACE by transient inhibition or permanent genomic deletion
      results in a relative abundance of substance P (SP) and bradykinin (BK); this
      augments murine allergic contact dermatitis (ACD) by affecting ACD sensitization
      and elicitation, which involves neurokinin 1 receptors (NK1), BK receptors (B2)
      and an intact cutaneous sensory nervous system. Present evidence suggests that
      increased SP via NK(1) is capable of boosting important functions of SP- and NK1
      expressing dendritic cells (DCs) and T cells (TCs) in an auto- or paracrine
      manner, which promotes ACD antigen sensitization. Moreover, skin inflammation or
      wounding in vivo, as well as treatment of epidermal and dermal cells by UV light
      and inflammatory mediators in vitro, regulates NEP and ACE expression and
      activity. Likewise, NEP and ACE are capable of processing neuroendocrine
      hormones, such as adrenocorticotropin and alpha-melanocyte-stimulating hormone.
      Thus, present data indicate that ACE and NEP, via proteolytic cleavage of peptide
      mediators and growth factors, represent important control factors for the
      inflammatory response in skin disorders such as psoriasis or allergic
      inflammation, but may also be capable of affecting pigmentation, cell survival,
      wound healing and tissue regeneration.

PMID- 15507109
TI  - Novel aspects in cutaneous biology of acetylcholine synthesis and acetylcholine
      receptors.
AB  - Extraneuronal acetylcholine (ACh) has been demonstrated to influence a plethora
      of cutaneous cell functions in an autocrine, paracrine and endocrine fashion.
      Through the differentiation-specific expression of its different nicotinic (nACh
      R) and muscarinic (mACh-R) receptors, ACh acts upon keratinocyte proliferation
      and migration, terminal differentiation and barrier formation, sweat and sebum
      secretion as well as microcirculation and angiogenesis. Only very recently it has
      been recognized that acetylcholinesterase, but not cholineacetyltransferase,
      activity is regulated by hydrogen peroxide. Considering that the outer layer of
      the human skin can be a target for UV-generated H2O2 in the millimolar range,
      this mechanism needs to be taken into account for the regulation of ACh
      homeostasis in skin biology. Consequently, ACh can accumulate, as shown, for
      example, in the depigmentation process in vitiligo. There is a highly regulated
      distribution of ACh-R in human epidermis and adnexal structures, supporting
      previously observed effects of cholinergic compounds on keratinocyte biology.
      Most significantly, the regulated expression of ACh-R in sebaceous glands
      advocates a role for ACh in sebum production and as a promoter of sebocyte
      differentiation, thus offering an explanation for skin diseases associated with
      altered sebum production after chronic nicotine exposure. So far, ACh-induced
      sweat production has been thought to be under the exclusive control of mACh-R.
      However, recently, the presence of both different nACh-R and mACh-R in
      myoepithelial and acinar cells of eccrine sweat glands has been documented,
      indicating a more complex regulation of sweat production and expulsion.

PMID- 15507110
TI  - Neuroendocrine regulation of sebocytes -- a pathogenetic link between stress and
      acne.
AB  - A causative link between emotional stress and acne has long been postulated.
      There is mounting evidence that the molecular mechanism underlying this
      observation is related to the expression of receptors for several neuroendocrine
      mediators by the sebaceous gland. Recent and ongoing studies have indicated that
      human sebocytes express functional receptors for corticotropin-releasing hormone,
      melanocortins, beta-endorphin, vasoactive intestinal polypeptide, neuropeptide Y
      and calcitonin gene-related peptide. After ligand binding, these receptors
      modulate the production of inflammatory cytokines, proliferation,
      differentiation, lipogenesis and androgen metabolism in sebocytes. By means of
      their autocrine, paracrine and endocrine actions, these neuroendocrine factors
      appear to mediate centrally and topically induced stress towards the sebaceous
      gland, ultimately affecting the clinical course of acne.

PMID- 15507111
TI  - Skin aging and sex hormones in women -- clinical perspectives for intervention by
      hormone replacement therapy.
AB  - The skin, the largest organ of the body, is the organ in which changes associated
      with aging are most visible. The skin is a target organ for various hormones, and
      sex steroids have a profound influence on the aging process. A decrease in sex
      steroids thus induces a reduction of those skin functions that are under hormonal
      control. Keratinocytes, Langerhans' cells, melanocytes, sebaceous glands,
      collagen content and the synthesis of hyaluronic acid, for example, are under
      hormonal influence. Topical application of estrogens has a positive effect on
      skin aging parameters, whilst numerous studies have also shown the positive
      influence of systemic hormone replacement therapy on skin aging. As an
      alternative treatment, phytohormones may be administered, with the structural
      similarity to 17beta-estradiol explaining their estrogen-like effects. However,
      isoflavonoids exhibit an inferior biological potency to synthetic estrogens.
      Although a large number of publications have documented the effects of sex
      hormones on the aging process, it is obvious that hormone replacement should not
      be administered as an independent treatment for skin aging.

PMID- 15507112
TI  - Point mutations of 3BP2 identified in human-inherited disease cherubism result in
      the loss of function.
AB  - Adaptor protein 3BP2 positively regulates the high affinity IgE receptor
      (FcepsilonRI)-mediated activation of degranulation in mast cells. Genetic study
      identified the point mutations of 3BP2 gene in human-inherited disease cherubism.
      The multiple cysts in cherubism lesion of jaw bones are filled with the activated
      osteoclasts and stromal cells, including mast cells. By over-expression study
      using rat basophilic leukaemia RBL-2H3 mast cells, we have analysed the effect of
      the point mutations on the function of 3BP2 protein, which plays a positive
      regulatory role on FcepsilonRI-mediated mast cell activation. Over-expression of
      3BP2 mutants suppressed the antigen-induced degranulation and cytokine gene
      transcription. Antigen-induced phosphorylation of Vav1, activation of Rac1,
      extracellular signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38
      mitogen activated protein kinase (MAPK), inhibitor of nuclear factor kappaB
      kinase (IKK) and nuclear factor of activated T cells (NFAT) were all impaired in
      the cells over-expressing the cherubism mutants of 3BP2. Furthermore, cherubism
      mutations of 3BP2 may abrogate the binding ability to interact with chaperone
      protein 14-3-3. These results demonstrate that over-expression of the mutant form
      of 3BP2 inhibits the antigen-induced mast cell activation. It suggests that point
      mutations of 3BP2 gene cause the dysfunction of 3BP2 in vivo.

PMID- 15507113
TI  - Cellular and molecular studies of B cells exhibiting reverse somatic mutation
      throughout life.
AB  - Somatic mutation of immunoglobulin (Ig) genes plays an important role in
      generating antibody diversity. The frequency of somatic mutation appears to vary
      throughout life. However, this process has been difficult to study in vivo
      because the DNA in and around rearranged V genes undergoes random mutation,
      causing silent or replacement mutations. Therefore, we have developed a
      transgenic mouse model for studying the frequency of B cells exhibiting mutation
      in young and old mice. The system is based on a reporter transgene (HuG-X) that
      encodes a chimeric Ig heavy chain composed of a murine VDJ segment and a human
      IgG1 constant region. The VDJ has been mutated to contain a TAG stop codon in the
      D segment. Therefore, the transgene is transcribed but not translated. Point
      mutation of the stop codon results in expression of the chimeric H chain, which
      is readily detected as human IgG1 expression. In vivo, we found that the
      transgene undergoes spontaneous reverse somatic mutation at a low frequency.
      Treatment of HuG-X mice with anti-IgD greatly increases the frequency of somatic
      mutation. The observed mutation frequency in anti-IgD-treated mice increases with
      age until adulthood, then plateaux and finally declines in aged mice. The
      mutations in the stop codon were associated with increased double-stranded DNA
      breaks (DSB) within and around the TAG site. Our results demonstrate that the
      rate of frequency of spontaneous reverse mutation is very low in vivo, yet it is
      significantly increased after stimulation with anti-IgD antibodies. The frequency
      of point mutation is age dependent and correlates with increased DSB.

PMID- 15507114
TI  - The transactivating function of peroxisome proliferator-activated receptor gamma
      is negatively regulated by SUMO conjugation in the amino-terminal domain.
AB  - Peroxisome proliferator-activated receptor (PPAR)-gamma2, a member of the nuclear
      hormone receptor superfamily, plays a key role in adipocyte differentiation. Its
      amino-terminal region carries a ligand-independent gene-activating function, AF
      1, and is composed of activation as well as repression domains. We have found
      PPARgamma2 and its isoform, PPARgamma1, to be modified by small ubiquitin-related
      modifier (SUMO)-1 in vivo, at a lysine residue in the repression domain. In
      reporter assays, a sumoylation-defective K107R mutant of PPARgamma2 exhibited
      much stronger transactivation than the wild-type, comparable with that of a
      mutant deleted for the repression domain. A close inverse correlation was
      observed between the levels of sumoylation and transactivation by PPARgamma2, in
      analyses employing PPARgamma2 forms with mutations in the sumoylation motif and a
      dominant-negative mutant of the SUMO conjugating enzyme, Ubc9. Studies with
      phosphorylation-defective mutants suggested that phosphorylation at S112 of
      PPARgamma2 promotes K107 sumoylation, and this latter exerts the more potent
      repressive effects. The K107R mutant PPARgamma2, when infected into NIH3T3 cells
      with a viral vector, promoted differentiation into adipocytes more efficiently
      than the wild-type. These observations provide evidence that sumoylation is
      involved in negative regulation of the transactivating function of PPARgamma2.

PMID- 15507115
TI  - Rad18/Rad5/Mms2-mediated polyubiquitination of PCNA is implicated in replication
      completion during replication stress.
AB  - Ubiquitination of proteins was previously shown to modulate various processes of
      DNA metabolism. PCNA, a processivity factor with essential functions in
      replication and repair, is modified with ubiquitin at K164. In addition, PCNA is
      sumoylated at K127 and K164. We found that the rad18delta mutation suppresses the
      temperature sensitivity of the polymerase delta mutants hys2-1 and cdc2-1 as well
      as the synthetic lethality of cdc2-1 pol32delta mutants, suggesting a role for
      Rad18 in modulating DNA replication. As Rad18 mediates ubiquitination of PCNA, we
      examined whether PCNA modifications affected its function in replication.
      Multicopy PCNA alleviated the replication defects of rfc5-1 strains, but not
      those of poldelta mutants. In contrast, multicopy PCNA-K164R had reduced ability
      to suppress the replication defects of rfc5-1, but alleviated those of poldelta
      mutants. The roles of sumoylated and ubiquitinated PCNA in rfc5-1 and hys2-1
      mutants were addressed by using mutant backgrounds that selectively affected
      sumoylation (siz1delta), ubiquitination (rad18delta), polyubiquitination
      (rad5delta, mms2delta), or the ability of cells to perform translesion synthesis
      (polzetadelta, poletadelta). Our results are consistent with the idea that the
      Rad18/Rad5/Mms2 polyubiquitination pathway is important for replication
      completion, perhaps by promoting a template switch type of DNA synthesis.

PMID- 15507116
TI  - Locus control region elements HS2 and HS3 in combination with chromatin
      boundaries confer high-level expression of a human beta-globin transgene in a
      centromeric region.
AB  - Expression constructs are subject to position-effects in transgenic assays unless
      they harbour elements that protect them from negative or positive influences
      exerted by chromatin at the site of integration. Locus control regions (LCRs) and
      boundary elements are able to protect from position effects by preventing
      heterochromatization of linked genes. The LCR in the human beta-globin gene locus
      is located far upstream of the genes and composed of several erythroid specific
      DNase I hypersensitive (HS) sites. Previous studies demonstrated that the LCR HS
      sites act synergistically to confer position-independent and high-level globin
      gene expression at different integration sites in transgenic mice. Here we show
      that LCR HS sites 2 and 3, in combination with boundary elements derived from the
      chicken beta-globin gene locus, confer high-level human beta-globin gene
      expression in different chromosomal integration sites in transgenic mice.
      Moreover, we found that the construct is accessible to nucleases and highly
      expressed when integrated in a centromeric region. These results demonstrate that
      the combination of enhancer, chromatin opening and boundary activities can
      establish independent expression units when integrated into chromatin.

PMID- 15507117
TI  - ASC is essential for LPS-induced activation of procaspase-1 independently of TLR
      associated signal adaptor molecules.
AB  - Toll-like receptors (TLRs) initiate a signalling cascade via association with an
      adaptor molecule, myeloid differentiation factor 88 (MyD88) and/or TIR domain
      containing adaptor inducing-IFN-beta (Trif), to induce various pro-inflammatory
      cytokines for microbial eradication. After stimulation of TLR4 with
      lipopolysaccharide (LPS), both IL-1beta and IL-18 are processed, depending on the
      activation of caspase-1, although its mechanism remains unclear. ASC is an
      adapter protein possibly involved in the activation of procaspase-1. To unravel
      the requirement of ASC, we generated Asc(-/-) mice. Upon stimulation with LPS,
      Asc(-/-) macrophages failed in the processing of procaspase-1 and maturation of
      pro-IL-1beta and pro-IL-18, but normally produced other pro-inflammatory
      cytokines including TNF-alpha and IL-6. MyD88(-/-) and Trif(-/-) macrophages
      showed normal activation of caspase-1, demonstrating a dispensable role for MyD88
      and Trif. After, LPS-challenged Asc(-/-) mice lacked serum elevation of IL-1beta
      and IL-18. Moreover, the Asc(-/-) mice exhibited neither acute liver injury nor
      lethal shock. These results demonstrate critical roles for ASC in the release of
      IL-1beta/IL-18 via activation of caspase-1 and provide new insights into the
      inflammatory responses for host defence and diseases.

PMID- 15507118
TI  - An interactive gene network for securin-separase, condensin, cohesin, Dis1/Mtc1
      and histones constructed by mass transformation.
AB  - The small genome of fission yeast Schizosaccharomyces pombe contains 4824
      predicted genes and gene disruption suggests that approximately 850 are essential
      for viability. To obtain information on interactions among genes required for
      chromosome segregation, an approach called Strategy B was taken using mass
      transformation of the 1015 temperature-sensitive (ts) mutants that were made by
      random mutagenesis and transformed by plasmids carrying the genes for securin,
      separase, condensin, cohesin, kinetochore microtubule-binding proteins Dis1/Mtc1
      or histones. Mutant strains whose phenotypes were either suppressed or inhibited
      by plasmids were selected. Each plasmid interacted positively or negatively with
      the average 14 strains. Identification of the mutant gene products by cloning
      revealed many hitherto unknown interactions. The interactive networks of
      segregation therefore may consist of genes with a variety of functions. For
      example, separase/Cut1 interacts with Cdc48/p97/VCP, which stabilizes securin and
      separase. Surprisingly, S. pombe cdc48 mutants displayed the mitotic phenotype
      highly similar to separase/cut1 mutants. This approach also provides a novel way
      of mutant isolation, resulting in two histone H2B strains and a cohesion mutant
      with a new phenotype.

PMID- 15507119
TI  - Targeted disruption of the mouse ELYS gene results in embryonic death at peri
      implantation development.
AB  - Early mouse development is a complicated process that is controlled by various
      proteins including transcription factors. Recently, we identified a putative
      transcription factor, ELYS (embryonic large molecule derived from yolk sac),
      using a subtraction strategy. To elucidate the role of ELYS in vivo, we generated
      ELYS-deficient mice by homologous recombination. Although heterozygous mice
      appeared to be healthy, fertile and normal, embryos homozygous for the ELYS
      mutation died between embryonic day (E) 3.5 and 5.5. Null mutant blastocysts
      collected from the uterus at E3.5 were viable and indistinguishable from wild
      type littermates. However, when cultured in vitro, they showed impaired
      proliferation of the inner cells, because of apoptosis. The expression of ELYS
      mRNA was detected in both the inner cell mass (ICM) and the trophectoderm at the
      blastocyst stage, and persisted throughout the developing embryo during E4.5 to
      6.5. These results indicate that ELYS is a critical factor for early mouse
      development and is essential for the survival of the inner cells.

PMID- 15507120
TI  - MFB-1, an F-box-type ubiquitin ligase, regulates TGF-beta signalling.
AB  - TGF-beta signalling regulates cell growth, differentiation, morphogenesis and
      apoptosis. MAFbx/Atrogin-1 has been identified as a regulator for skeletal muscle
      atrophy and encodes an F-box-type E3 ubiquitin ligase. However, little is known
      about how MAFbx/Atrogin-1 regulates cellular signalling. Here, we identify and
      genetically characterize MFB-1, a MAFbx/Atrogin-1 homologue from Caenorhabditis
      elegans. The mfb-1 deletion mutant significantly enhanced the dauer constitutive
      (Daf-c) phenotype caused by mutations in the DAF-7/TGF-beta-like signalling
      pathway, but not the DAF-2/insulin receptor-like signalling pathway. Conversely,
      the Daf-c phenotypes of DAF-7 pathway mutants were partially suppressed by mfb-1
      cDNA transgenes. Therefore, MFB-1 acts genetically downstream in the DAF-7
      pathway. A mfb-1::GFP fusion was found to be expressed in the nervous system,
      hypodermis and intestine and overlapped expression of many DAF-7 pathway genes.
      We propose that MFB-1 is a novel F-box protein that negatively regulates dauer
      formation in concert with the DAF-7 signalling pathway in C. elegans.

PMID- 15507121
TI  - Internucleosomal DNA cleavage in apoptotic WEHI 231 cells is mediated by a
      chymotrypsin-like protease.
AB  - Although several lines of evidence support a role for serine proteases in
      apoptosis, little is known about the mechanisms involved. In the present study,
      we have examined the apoptosis-inducing potential and dissected the death
      signalling pathways of N-tosyl-L-phenylalanine chloromethyl ketone (TPCK) and N
      tosyl-L-lysine chloromethyl ketone (TLCK), inhibitors of chymotrypsin- and
      trypsin-like proteases, respectively. Our results designate two distinct roles
      for serine proteases. Firstly, we show that both inhibitors induce biochemical
      and morphological characteristics of apoptosis, including proteolysis of poly(ADP
      ribose) polymerase 1 (PARP-1) and inhibitor of caspase-activated DNase (ICAD), as
      well as mitochondrial dysfunction, and that their action is abrogated by the
      caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp.fluoromethylketone (z-VAD.fmk).
      These results suggest that inhibition of anti-apoptotic serine proteases governs
      the onset of the caspase-dependant apoptotic cascade. Secondly, we also
      demonstrate the involvement of a serine protease in the terminal stage of
      apoptosis. We showed that chymotrypsin-like protease activity is required for
      internucleosomal DNA fragmentation in apoptotic cells. Hence, DNA fragmentation
      is abrogated in TPCK-pre-treated WEHI 231 cells undergoing apoptosis triggered
      either by anti-IgM or TLCK. These results indicate that internucleosomal DNA
      cleavage in apoptotic cells is mediated by a chymotrypsin-like protease.

PMID- 15507122
TI  - Peroxisome proliferator-activated receptor gamma-dependent and -independent
      growth inhibition of gastrointestinal tumour cells.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) acts as a ligand
      activated transcription factor. Although ligand-induced cellular differentiation
      and growth inhibition have been mostly studied on human cancers expressing
      PPARgamma, it is unclear if the transcriptional activation of PPARgamma is the
      main mechanism of growth inhibition. In this study, we investigated whether there
      is a link between growth inhibitory effect and transcriptional activation of
      PPARgamma in several gastrointestinal tumour cell lines. The transcriptional
      activation potential of PPARgamma was assessed by reporter gene assay employing a
      PPRE-luciferase vector, and growth inhibitory effect of PPARgamma was
      investigated by (3)H-thymidine incorporation assay, in the presence or absence of
      thiazolidinedione ligands, rosiglitazone and troglitazone. As expected, in the
      case of cell lines positive for the transcriptional activation potential of
      PPARgamma (T.Tn, MKN-45 and LoVo), both the ligands induced growth inhibition.
      However, in case of some other cell lines negative for the transcriptional
      activation potential of PPARgamma (TT, AGS and HCT-15), troglitazone still showed
      a growth inhibitory effect. Administration of the PPARgamma antagonist GW9662 did
      not reverse this growth inhibitory activity of troglitazone. The introduction of
      dominant negative mutants of PPARgamma did not suppress the activity either.
      These observations suggest that while rosiglitazone inhibits cellular growth
      predominantly through transcriptional activation of PPARgamma, troglitazone can
      induce it both in PPARgamma-dependent and -independent pathways.

PMID- 15507123
TI  - GRIP1tau, a novel PDZ domain-containing transcriptional activator, cooperates
      with the testis-specific transcription elongation factor SII-T1.
AB  - SII-T1 is a tissue-specific member of the transcription elongation factor S-II
      that is expressed specifically in male germ cells. In the present study, we have
      identified a protein named GRIP1tau interacting with SII-T1 by yeast two-hybrid
      screening. GRIP1tau is a novel isoform of glutamate receptor-interacting protein
      1 (GRIP1) that associates with the cytoplasmic domain of the alpha-amino-3
      hydroxy-5-methyl-4-isoaxazolepropionate (AMPA)-type glutamate receptor. GRIP1tau
      is a testis-specific nuclear protein that activates transcription when fused with
      a GAL4 DNA binding domain in GAL4-responsive reporter gene assays. The
      transactivation domain of GRIP1tau overlapped with the region essential for
      interaction with SII-T1, as revealed by co-immunoprecipitation assays. Also,
      transactivation by GRIP1tau was stimulated by SII-T1 in a dose-dependent manner.
      Therefore, we propose that GRIP1tau is a novel testis-specific transcriptional
      activator regulated by interaction with the testis-specific transcription
      elongation factor SII-T1.

PMID- 15507125
TI  - Divergence of the mRNA targets for the Ssb proteins of bacteriophages T4 and
      RB69.
AB  - The single-strand binding (Ssb) protein of phage T4 (T4 gp32, product of gene 32)
      is a mRNA-specific autogenous translational repressor, in addition to being a
      sequence-independent ssDNA-binding protein that participates in phage DNA
      replication, repair and recombination. It is not clear how this physiologically
      essential protein distinguishes between specific RNA and nonspecific nucleic acid
      targets. Here, we present phylogenetic evidence suggesting that ssDNA and
      specific RNA bind the same gp32 domain and that plasticity of this domain
      underlies its ability to configure certain RNA structures for specific binding.
      We have cloned and characterized gene 32 of phage RB69, a relative of T4 We
      observed that RB69 gp32 and T4 gp32 have nearly identical ssDNA binding domains,
      but diverge in their C-terminal domains. In T4 gp32, it is known that the C
      terminal domain interacts with the ssDNA-binding domain and with other phage
      induced proteins. In translation assays, we show that RB69 gp32 is, like T4 gp32,
      an autogenous translational repressor. We also show that the natural mRNA targets
      (translational operators) for the 2 proteins are diverged in sequence from each
      other and yet can be repressed by either gp32. Results of chemical and RNase
      sensitivity assays indicate that the gp32 mRNA targets from the 2 related phages
      have similar structures, but differ in their patterns of contact with the 2
      repressors. These and other observations suggest that a range of gp32-RNA binding
      specificities may evolve in nature due to plasticity of the protein-nucleic acid
      interaction and its response to modulation by the C-terminal domain of this
      translational repressor.

PMID- 15507127
TI  - Impact of seasonal variation, age and smoking status on human semen parameters:
      The Massachusetts General Hospital experience.
AB  - BACKGROUND: To investigate the relationship of human semen parameters with
      season, age and smoking status. METHODS: The present study used data from
      subjects recruited into an ongoing cross-sectional study on the relationship
      between environmental agents and semen characteristics. Our population consisted
      of 306 patients who presented to the Vincent Memorial Andrology Laboratory of
      Massachusetts General Hospital for semen evaluation. Sperm concentration and
      motility were measured with computer aided sperm analysis (CASA). Sperm
      morphology was scored using Tygerberg Kruger strict criteria. Regression analyses
      were used to investigate the relationships between semen parameters and season,
      age and smoking status, adjusting for abstinence interval. RESULTS: Sperm
      concentration in the spring was significantly higher than in winter, fall and
      summer (p < 0.05). There was suggestive evidence of higher sperm motility and
      percent of sperm with normal morphology in the spring than in the other seasons.
      There were no statistically significant relationships between semen parameters
      and smoking status, though current smokers tended to have lower sperm
      concentration. We also did not find a statistically significant relationship
      between age and semen parameters. CONCLUSIONS: We found seasonal variations in
      sperm concentration and suggestive evidence of seasonal variation in sperm
      motility and percent sperm with normal morphology. Although smoking status was
      not a significant predictor of semen parameters, this may have been due to the
      small number of current smokers in the study.

PMID- 15507126
TI  - Persistent expression of chemokine and chemokine receptor RNAs at primary and
      latent sites of herpes simplex virus 1 infection.
AB  - Inflammatory cytokines and infiltrating T cells are readily detected in herpes
      simplex virus (HSV) infected mouse cornea and trigeminal ganglia (TG) during the
      acute phase of infection, and certain cytokines continue to be expressed at lower
      levels in infected TG during the subsequent latent phase. Recent results have
      shown that HSV infection activates Toll-like receptor signaling. Thus, we
      hypothesized that chemokines may be broadly expressed at both primary sites and
      latent sites of HSV infection for prolonged periods of time. Real-time reverse
      transcriptase-polymrease chain reaction (RT-PCR) to quantify expression levels of
      transcripts encoding chemokines and their receptors in cornea and TG following
      corneal infection. RNAs encoding the inflammatory-type chemokine receptors CCR1,
      CCR2, CCR5, and CXCR3, which are highly expressed on activated T cells,
      macrophages and most immature dendritic cells (DC), and the more broadly
      expressed CCR7, were highly expressed and strongly induced in infected cornea and
      TG at 3 and 10 days postinfection (dpi). Elevated levels of these RNAs persisted
      in both cornea and TG during the latent phase at 30 dpi. RNAs for the broadly
      expressed CXCR4 receptor was induced at 30 dpi but less so at 3 and 10 dpi in
      both cornea and TG. Transcripts for CCR3 and CCR6, receptors that are not highly
      expressed on activated T cells or macrophages, also appeared to be induced during
      acute and latent phases; however, their very low expression levels were near the
      limit of our detection. RNAs encoding the CCR1 and CCR5 chemokine ligands MIP
      1alpha, MIP-1beta and RANTES, and the CCR2 ligand MCP-1 were also strongly
      induced and persisted in cornea and TG during the latent phase. These and other
      recent results argue that HSV antigens or DNA can stimulate expression of
      chemokines, perhaps through activation of Toll-like receptors, for long periods
      of time at both primary and latent sites of HSV infection. These chemokines
      recruit activated T cells and other immune cells, including DC, that express
      chemokine receptors to primary and secondary sites of infection. Prolonged
      activation of chemokine expression could provide mechanistic explanations for
      certain aspects of HSV biology and pathogenesis.

PMID- 15507128
TI  - The missed lessons of Sir Austin Bradford Hill.
AB  - Austin Bradford Hill's landmark 1965 paper contains several important lessons for
      the current conduct of epidemiology. Unfortunately, it is almost exclusively
      cited as the source of the "Bradford-Hill criteria" for inferring causation when
      association is observed, despite Hill's explicit statement that cause-effect
      decisions cannot be based on a set of rules. Overlooked are Hill's important
      lessons about how to make decisions based on epidemiologic evidence. He advised
      epidemiologists to avoid over-emphasizing statistical significance testing, given
      the observation that systematic error is often greater than random error. His
      compelling and intuitive examples point out the need to consider costs and
      benefits when making decisions about health-promoting interventions. These
      lessons, which offer ways to dramatically increase the contribution of health
      science to decision making, are as needed today as they were when Hill presented
      them.

PMID- 15507129
TI  - Resistant starch consumption promotes lipid oxidation.
AB  - BACKGROUND: Although the effects of resistant starch (RS) on postprandial
      glycemia and insulinemia have been extensively studied, little is known about the
      impact of RS on fat metabolism. This study examines the relationship between the
      RS content of a meal and postprandial/post-absorbative fat oxidation. RESULTS: 12
      subjects consumed meals containing 0%, 2.7%, 5.4%, and 10.7% RS (as a percentage
      of total carbohydrate). Blood samples were taken and analyzed for glucose,
      insulin, triacylglycerol (TAG) and free fatty acid (FFA) concentrations.
      Respiratory quotient was measured hourly. The 0%, 5.4%, and 10.7% meals contained
      50 muCi [1-14C]-triolein with breath samples collected hourly following the meal,
      and gluteal fat biopsies obtained at 0 and 24 h. RS, regardless of dose, had no
      effect on fasting or postprandial insulin, glucose, FFA or TAG concentration, nor
      on meal fat storage. However, data from indirect calorimetry and oxidation of [1
      14C]-triolein to 14CO2 showed that addition of 5.4% RS to the diet significantly
      increased fat oxidation. In fact, postprandial oxidation of [1-14C]-triolein was
      23% greater with the 5.4% RS meal than the 0% meal (p = 0.0062). CONCLUSIONS:
      These data indicate that replacement of 5.4% of total dietary carbohydrate with
      RS significantly increased post-prandial lipid oxidation and therefore could
      decrease fat accumulation in the long-term.

PMID- 15507130
TI  - A further critique of the analytic strategy of adjusting for covariates to
      identify biologic mediation.
AB  - BACKGROUND: Epidemiologic research is often devoted to etiologic investigation,
      and so techniques that may facilitate mechanistic inferences are attractive. Some
      of these techniques rely on rigid and/or unrealistic assumptions, making the
      biologic inferences tenuous. The methodology investigated here is effect
      decomposition: the contrast between effect measures estimated with and without
      adjustment for one or more variables hypothesized to lie on the pathway through
      which the exposure exerts its effect. This contrast is typically used to
      distinguish the exposure's indirect effect, through the specified intermediate
      variables, from its direct effect, transmitted via pathways that do not involve
      the specified intermediates. METHODS: We apply a causal framework based on latent
      potential response types to describe the limitations inherent in effect
      decomposition analysis. For simplicity, we assume three measured binary variables
      with monotonic effects and randomized exposure, and use difference contrasts as
      measures of causal effect. Previous authors showed that confounding between
      intermediate and the outcome threatens the validity of the decomposition
      strategy, even if exposure is randomized. We define exchangeability conditions
      for absence of confounding of causal effects of exposure and intermediate, and
      generate two example populations in which the no-confounding conditions are
      satisfied. In one population we impose an additional prohibition against unit
      level interaction (synergism). We evaluate the performance of the decomposition
      strategy against true values of the causal effects, as defined by the proportions
      of latent potential response types in the two populations. RESULTS: We
      demonstrate that even when there is no confounding, partition of the total effect
      into direct and indirect effects is not reliably valid. Decomposition is valid
      only with the additional restriction that the population contain no units in
      which exposure and intermediate interact to cause the outcome. This restriction
      implies homogeneity of causal effects across strata of the intermediate.
      CONCLUSIONS: Reliable effect decomposition requires not only absence of
      confounding, but also absence of unit-level interaction and use of linear
      contrasts as measures of causal effect. Epidemiologists should be wary of
      etiologic inference based on adjusting for intermediates, especially when using
      ratio effect measures or when absence of interacting potential response types
      cannot be confidently asserted.

PMID- 15507131
TI  - The J-shape association of ethanol intake with total homocysteine concentrations:
      the ATTICA study.
AB  - BACKGROUND: Epidemiological studies suggest a non-monotonic effect of alcohol
      consumption on cardiovascular risk, while there is strong evidence concerning the
      involvement of homocysteine levels on thrombosis. The aim of this work was to
      evaluate the association between usual ethanol consumption and homocysteine
      levels, in cardiovascular disease free adults. METHODS: From May 2001 to December
      2002 we randomly enrolled 1514 adult men and 1528 women, without any evidence of
      cardiovascular disease, stratified by age - gender (census 2001), from the
      greater area of Athens, Greece. Among the variables ascertained we measured the
      daily ethanol consumption and plasma homocysteine concentrations. RESULTS: Data
      analysis revealed a J-shape association between ethanol intake (none, <12 gr, 12 
      24 gr, 25 - 48 gr, >48 gr per day) and total homocysteine levels (mean +/-
      standard deviation) among males (13 +/- 3 vs. 11 +/- 3 vs. 14 +/- 4 vs. 18 +/- 5
      vs. 19 +/- 3 mumol/L, respectively, p < 0.01) and females (10 +/- 4 vs. 9 +/- 3
      vs. 11 +/- 3 vs. 15 +/- 4 vs. 17 +/- 3 mumol/L, respectively, p < 0.01), after
      controlling for several potential confounders. The lowest homocysteine
      concentrations were observed with ethanol intake of < 12 gr/day (Bonferroni
      alpha* < 0.05). No differences were observed when we stratified our analysis by
      type of alcoholic beverage consumed. CONCLUSION: We observed a J-shape
      relationship between homocysteine concentrations and the amount of ethanol
      usually consumed.

PMID- 15507133
TI  - Management of multifactorial idiopathic epilepsy in EL mice with caloric
      restriction and the ketogenic diet: role of glucose and ketone bodies.
AB  - BACKGROUND: The high fat, low carbohydrate ketogenic diet (KD) was developed as
      an alternative to fasting for seizure management. While the mechanisms by which
      fasting and the KD inhibit seizures remain speculative, alterations in brain
      energy metabolism are likely involved. We previously showed that caloric
      restriction (CR) inhibits seizure susceptibility by reducing blood glucose in the
      epileptic EL mouse, a natural model for human multifactorial idiopathic epilepsy.
      In this study, we compared the antiepileptic and anticonvulsant efficacy of the
      KD with that of CR in adult EL mice with active epilepsy. EL mice that
      experienced at least 15 recurrent complex partial seizures were fed either a
      standard diet unrestricted (SD-UR) or restricted (SD-R), and either a KD
      unrestricted (KD-UR) or restricted (KD-R). All mice were fasted for 14 hrs prior
      to diet initiation. A new experimental design was used where each mouse in the
      diet-restricted groups served as its own control to achieve a 20-23% body weight
      reduction. Seizure susceptibility, body weights, and the levels of plasma glucose
      and beta-hydroxybutyrate were measured once/week over a nine-week treatment
      period. RESULTS: Body weights and blood glucose levels remained high over the
      testing period in the SD-UR and the KD-UR groups, but were significantly (p <
      0.001) reduced in the SD-R and KD-R groups. Plasma beta-hydroxybutyrate levels
      were significantly (p < 0.001) increased in the SD-R and KD-R groups compared to
      their respective UR groups. Seizure susceptibility remained high in both UR-fed
      groups throughout the study, but was significantly reduced after three weeks in
      both R-fed groups. CONCLUSIONS: The results indicate that seizure susceptibility
      in EL mice is dependent on plasma glucose levels and that seizure control is more
      associated with the amount than with the origin of dietary calories. Also, CR
      underlies the antiepileptic and anticonvulsant action of the KD in EL mice. A
      transition from glucose to ketone bodies for energy is predicted to manage EL
      epileptic seizures through multiple integrated changes of inhibitory and
      excitatory neural systems.

PMID- 15507132
TI  - Uric acid: A new look at an old risk marker for cardiovascular disease, metabolic
      syndrome, and type 2 diabetes mellitus: The urate redox shuttle.
AB  - BACKGROUND: The topical role of uric acid and its relation to cardiovascular
      disease, renal disease, and hypertension is rapidly evolving. Its important role
      both historically and currently in the clinical clustering phenomenon of the
      metabolic syndrome (MS), type 2 diabetes mellitus (T2DM), atheroscleropathy, and
      non-diabetic atherosclerosis is of great importance. RESULTS: Uric acid is a
      marker of risk and it remains controversial as to its importance as a risk factor
      (causative role). In this review we will attempt to justify its important role as
      one of the many risk factors in the development of accelerated atherosclerosis
      and discuss its importance of being one of the multiple injurious stimuli to the
      endothelium, the arterial vessel wall, and capillaries. The role of uric acid,
      oxidative - redox stress, reactive oxygen species, and decreased endothelial
      nitric oxide and endothelial dysfunction cannot be over emphasized.In the
      atherosclerotic prooxidative environmental milieu the original antioxidant
      properties of uric acid paradoxically becomes prooxidant, thus contributing to
      the oxidation of lipoproteins within atherosclerotic plaques, regardless of their
      origins in the MS, T2DM, accelerated atherosclerosis (atheroscleropathy), or non
      diabetic vulnerable atherosclerotic plaques. In this milieu there exists an
      antioxidant - prooxidant urate redox shuttle. CONCLUSION: Elevations of uric acid
      > 4 mg/dl should be considered a "red flag" in those patients at risk for
      cardiovascular disease and should alert the clinician to strive to utilize a
      global risk reduction program in a team effort to reduce the complications of the
      atherogenic process resulting in the morbid - mortal outcomes of cardiovascular
      disease.

PMID- 15507134
TI  - Efficient activation of gene expression using a heat-shock inducible Gal4/Vp16
      UAS system in medaka.
AB  - BACKGROUND: Genetic interference by DNA, mRNA or morpholino injection is a widely
      used approach to study gene function in developmental biology. However, the lack
      of temporal control over the activity of interfering molecules often hampers
      investigation of gene function required during later stages of embryogenesis. To
      elucidate the roles of genes during embryogenesis a precise temporal control of
      transgene expression levels in the developing organism is on demand. RESULTS: We
      have generated a transgenic Gal4/Vp16 activator line that is heat-shock
      inducible, thereby providing a tool to drive the expression of specific effector
      genes via Gal4/Vp16. Merging the Gal4/Vp16-UAS system with the I-SceI
      meganuclease and the Sleeping Beauty transposon system allows inducible gene
      expression in an entirely uniform manner without the need to generate transgenic
      effector lines. Combination of this system with fluorescent protein reporters
      furthermore facilitates the direct visualization of transgene expressing cells in
      live embryos. CONCLUSION: The combinatorial properties of this expression system
      provide a powerful tool for the analysis of gene function during embryonic and
      larval development in fish by ectopic expression of gene products.

PMID- 15507135
TI  - Extractor for ESI quadrupole TOF tandem MS data enabled for high throughput batch
      processing.
AB  - BACKGROUND: Mass spectrometry based proteomics result in huge amounts of data
      that has to be processed in real time in order to efficiently feed identification
      algorithms and to easily integrate in automated environments. We present
      wiff2dta, a tool created to convert MS/MS data obtained using Applied Biosystem's
      QStar and QTrap 2000 and 4000 series. RESULTS: Comparing the performance of
      wiff2dta with the standard tools, we find wiff2dta being the fastest solution for
      extracting spectrum data from ABIs raw file format. wiff2dta is at least 10%
      faster than the standard tools. It is also capable of batch processing and can be
      easily integrated in high throughput environments. The program is freely
      available via http://www.protein-ms.de, http://sourceforge.net/projects/protms/
      and is also available from Applied Biosystems. CONCLUSIONS: wiff2dta offers the
      possibility to run as stand-alone application or within a batch process as
      command-line tool integrated in automation and high-throughput environments. It
      is more efficient than the state-of-the-art tools provided.

PMID- 15507136
TI  - TETRA: a web-service and a stand-alone program for the analysis and comparison of
      tetranucleotide usage patterns in DNA sequences.
AB  - BACKGROUND: In the emerging field of environmental genomics, direct cloning and
      sequencing of genomic fragments from complex microbial communities has proven to
      be a valuable source of new enzymes, expanding the knowledge of basic biological
      processes. The central problem of this so called metagenome-approach is that the
      cloned fragments often lack suitable phylogenetic marker genes, rendering the
      identification of clones that are likely to originate from the same genome
      difficult or impossible. In such cases, the analysis of intrinsic DNA-signatures
      like tetranucleotide frequencies can provide valuable hints on fragment
      affiliation. With this application in mind, the TETRA web-service and the TETRA
      stand-alone program have been developed, both of which automate the task of
      comparative tetranucleotide frequency analysis. AVAILABILITY:
      http://www.megx.net/tetra. RESULTS: TETRA provides a statistical analysis of
      tetranucleotide usage patterns in genomic fragments, either via a web-service or
      a stand-alone program. With respect to discriminatory power, such an analysis
      outperforms the assignment of genomic fragments based on the (G+C)-content, which
      is a widely-used sequence-based measure for assessing fragment relatedness. While
      the web-service is restricted to the calculation of correlation coefficients
      between tetranucleotide usage patterns of submitted DNA sequences, the stand
      alone program generates a much more detailed output, comprising all raw data and
      graphical plots. The stand-alone program is controlled via a graphical user
      interface and can batch-process a multitude of sequences. Furthermore, it comes
      with pre-computed tetranucleotide usage patterns for 166 prokaryote chromosomes,
      providing a useful reference dataset and source for data-mining. CONCLUSIONS: Up
      to now, the analysis of skewed oligonucleotide distributions within DNA sequences
      is not a commonly used tool within metagenomics. With the TETRA web-service and
      stand-alone program, the method is now accessible in an easy to use manner for a
      broad audience. This will hopefully facilitate the interrelation of genomic
      fragments from metagenome libraries, ultimately leading to new insights into the
      genetic potentials of yet uncultured microorganisms.

PMID- 15507137
TI  - Genomic imprinting and assisted reproduction.
AB  - Imprinted genes exhibit a parent-of-origin specific pattern of expression. Such
      genes have been shown to be targets of molecular defects in particular genetic
      syndromes such as Beckwith-Wiedemann and Angelman syndromes. Recent reports have
      raised concern about the possibility that assisted reproduction techniques, such
      as in vitro fertilization or intracytoplasmic sperm injection, might cause
      genomic imprinting disorders. The number of reported cases of those disorders is
      still too small to draw firm conclusions and the safety of these widely used
      assisted reproduction techniques needs to be further evaluated.

PMID- 15507138
TI  - Multivariate search for differentially expressed gene combinations.
AB  - BACKGROUND: To identify differentially expressed genes, it is standard practice
      to test a two-sample hypothesis for each gene with a proper adjustment for
      multiple testing. Such tests are essentially univariate and disregard the
      multidimensional structure of microarray data. A more general two-sample
      hypothesis is formulated in terms of the joint distribution of any sub-vector of
      expression signals. RESULTS: By building on an earlier proposed multivariate test
      statistic, we propose a new algorithm for identifying differentially expressed
      gene combinations. The algorithm includes an improved random search procedure
      designed to generate candidate gene combinations of a given size. Cross
      validation is used to provide replication stability of the search procedure. A
      permutation two-sample test is used for significance testing. We design a
      multiple testing procedure to control the family-wise error rate (FWER) when
      selecting significant combinations of genes that result from a successive
      selection procedure. A target set of genes is composed of all significant
      combinations selected via random search. CONCLUSIONS: A new algorithm has been
      developed to identify differentially expressed gene combinations. The performance
      of the proposed search-and-testing procedure has been evaluated by computer
      simulations and analysis of replicated Affymetrix gene array data on age-related
      changes in gene expression in the inner ear of CBA mice.

PMID- 15507139
TI  - Increased deep sleep in a medication-free, detoxified female offender with
      schizophrenia, alcoholism and a history of attempted homicide: case report.
AB  - BACKGROUND: Psychiatric sleep research has attempted to identify diagnostically
      sensitive and specific sleep patterns associated with particular disorders. Both
      schizophrenia and alcoholism are typically characterized by a severe sleep
      disturbance associated with decreased amounts of slow wave sleep, the
      physiologically significant, refreshing part of the sleep. Antisocial behaviour
      with severe aggression, on the contrary, has been reported to associate with
      increased deep sleep reflecting either specific brain pathology or a delay in the
      normal development of sleep patterns. The authors are not aware of previous sleep
      studies in patients with both schizophrenia and antisocial personality disorder.
      CASE PRESENTATION: The aim of the present case-study was to characterize the
      sleep architecture of a violent, medication-free and detoxified female offender
      with schizophrenia, alcoholism and features of antisocial personality disorder
      using polysomnography. The controls consisted of three healthy, age-matched women
      with no history of physical violence. The offender's sleep architecture was
      otherwise very typical for patients with schizophrenia and/or alcoholism, but an
      extremely high amount of deep sleep was observed in her sleep recording.
      CONCLUSIONS: The finding strengthens the view that severe aggression is related
      to an abnormal sleep pattern with increased deep sleep. The authors were able to
      observe this phenomenon in an antisocially behaving, violent female offender with
      schizophrenia and alcohol dependence, the latter disorders previously reported to
      be associated with low levels of slow wave sleep. New studies are, however,
      needed to confirm and explain this preliminary finding.

PMID- 15507140
TI  - Identification and utilization of inter-species conserved (ISC) probesets on
      Affymetrix human GeneChip platforms for the optimization of the assessment of
      expression patterns in non human primate (NHP) samples.
AB  - BACKGROUND: While researchers have utilized versions of the Affymetrix human
      GeneChip for the assessment of expression patterns in non human primate (NHP)
      samples, there has been no comprehensive sequence analysis study undertaken to
      demonstrate that the probe sequences designed to detect human transcripts are
      reliably hybridizing with their orthologs in NHP. By aligning probe sequences
      with expressed sequence tags (ESTs) in NHP, inter-species conserved (ISC)
      probesets, which have two or more probes complementary to ESTs in NHP, were
      identified on human GeneChip platforms. The utility of human GeneChips for the
      assessment of NHP expression patterns can be effectively evaluated by analyzing
      the hybridization behaviour of ISC probesets. Appropriate normalization methods
      were identified that further improve the reliability of human GeneChips for
      interspecies (human vs NHP) comparisons. RESULTS: ISC probesets in each of the
      seven Affymetrix GeneChip platforms (U133Plus2.0, U133A, U133B, U95Av2, U95B,
      Focus and HuGeneFL) were identified for both monkey and chimpanzee. Expression
      data was generated from peripheral blood mononuclear cells (PBMCs) of 12 human
      and 8 monkey (Indian origin Rhesus macaque) samples using the Focus GeneChip.
      Analysis of both qualitative detection calls and quantitative signal intensities
      showed that intra-species reproducibility (human vs. human or monkey vs. monkey)
      was much higher than interspecies reproducibility (human vs. monkey). ISC
      probesets exhibited higher interspecies reproducibility than the overall
      expressed probesets. Importantly, appropriate normalization methods could be
      leveraged to greatly improve interspecies correlations. The correlation
      coefficients between human (average of 12 samples) and monkey (average of 8
      Rhesus macaque samples) are 0.725, 0.821 and 0.893 for MAS5.0 (Microarray Suite
      version 5.0), dChip and RMA (Robust Multi-chip Average) normalization method,
      respectively. CONCLUSION: It is feasible to use Affymetrix human GeneChip
      platforms to assess the expression profiles of NHP for intra-species studies.
      Caution must be taken for interspecies studies since unsuitable probesets will
      result in spurious differentially regulated genes between human and NHP. RMA
      normalization method and ISC probesets are recommended for interspecies studies.

PMID- 15507141
TI  - The diagnostic value of endoscopy and Helicobacter pylori tests for peptic ulcer
      patients in late post-treatment setting.
AB  - BACKGROUND: Guidelines for management of peptic ulcer patients after the
      treatment are largely directed to detection of H. pylori infection using only non
      invasive tests. We compared the diagnostic value of non-invasive and endoscopy
      based H. pylori tests in a late post-treatment setting. METHODS: Altogether 34
      patients with dyspeptic complaints were referred for gastroscopy 5 years after
      the treatment of peptic ulcer using a one-week triple therapy scheme. The
      endoscopic and histologic findings were evaluated according to the Sydney
      classification. Bacteriological, PCR and cytological investigations and 13C-UBT
      tests were performed. RESULTS: Seventeen patients were defined H. pylori positive
      by 13C-UBT test, PCR and histological examination. On endoscopy, peptic ulcer
      persisted in 4 H. pylori positive cases. Among the 6 cases with erosions of the
      gastric mucosa, only two patients were H. pylori positive. Mucosal atrophy and
      intestinal metaplasia were revealed both in the H. pylori positive and H. pylori
      negative cases. Bacteriological examination revealed three clarithromycin
      resistant H. pylori strains. Cytology failed to prove validity for diagnosing H.
      pylori in a post-treatment setting. CONCLUSIONS: In a late post-treatment
      setting, patients with dyspepsia should not be monitored only by non-invasive
      investigation methods; it is also justified to use the classical histological
      evaluation of H. pylori colonisation, PCR and bacteriology as they have shown
      good concordance with 13C-UBT. Moreover, endoscopy and histological investigation
      of a gastric biopsy have proved to be the methods with an additional diagnostic
      value, providing the physician with information about inflammatory, atrophic and
      metaplastic lesions of the stomach in dyspeptic H. pylori positive and negative
      patients. Bacteriological methods are suggested for detecting the putative
      antimicrobial resistance of H. pylori, aimed at successful eradication of
      infection in persistent peptic ulcer cases.

PMID- 15507143
TI  - Screening for known mutations in EIF2B genes in a large panel of patients with
      premature ovarian failure.
AB  - BACKGROUND: Premature Ovarian Failure (POF), defined as the development of
      hypergonadotropic amenorrhea before the age of 40 years, occurs in about 1% of
      all women. Other than karyotype abnormalities, very few genes are known to be
      associated with this ovarian dysfunction. Recently, in seven patients who
      presented with POF and white matter abnormalities on MRI (ovarioleukodystrophy)
      eight mutationswere found in EIF2B2, 4 and 5. METHODS: To further test the
      involvement of known mutations of EIF2B genes in POF, we screened 93 patients
      with POF who did not have identified leukodystrophy or neurological symptoms. We
      evaluated these eight mutations and two additional mutations that had been found
      in patients with milder forms of eIF2B-related disorders. We used restriction
      enzymes and direct sequencing. RESULTS: None of the known mutations in EIF2B
      genes, either homozygous or heterozygous, were identified in our 93 patients with
      pure 46,XX POF. The upper 95 % confidence limit of the proportion 0/93 is 3.2%.
      CONCLUSIONS: We conclude that eIF2B mutations, already described in cases of POF
      associated with white matter abnormalities, are an uncommon cause of pure
      spontaneous premature ovarian failure.

PMID- 15507142
TI  - A probabilistic model for the evolution of RNA structure.
AB  - BACKGROUND: For the purposes of finding and aligning noncoding RNA gene- and cis
      regulatory elements in multiple-genome datasets, it is useful to be able to
      derive multi-sequence stochastic grammars (and hence multiple alignment
      algorithms) systematically, starting from hypotheses about the various kinds of
      random mutation event and their rates. RESULTS: Here, we consider a highly
      simplified evolutionary model for RNA, called "The TKF91 Structure Tree"
      (following Thorne, Kishino and Felsenstein's 1991 model of sequence evolution
      with indels), which we have implemented for pairwise alignment as proof of
      principle for such an approach. The model, its strengths and its weaknesses are
      discussed with reference to four examples of functional ncRNA sequences: a
      riboswitch (guanine), a zipcode (nanos), a splicing factor (U4) and a ribozyme
      (RNase P). As shown by our visualisations of posterior probability matrices, the
      selected examples illustrate three different signatures of natural selection that
      are highly characteristic of ncRNA: (i) co-ordinated basepair substitutions, (ii)
      co-ordinated basepair indels and (iii) whole-stem indels. CONCLUSIONS: Although
      all three types of mutation "event" are built into our model, events of type (i)
      and (ii) are found to be better modeled than events of type (iii). Nevertheless,
      we hypothesise from the model's performance on pairwise alignments that it would
      form an adequate basis for a prototype multiple alignment and genefinding tool.

PMID- 15507144
TI  - Real-time PCR quantitation of glucocorticoid receptor alpha isoform.
AB  - BACKGROUND: The expression of glucocorticoid-receptor (GR) seems to be a key
      mechanism in the regulation of glucocorticoid (GC) sensitivity and is potentially
      involved in cases of GC resistance or hypersensitivity. The aim of this study is
      to describe a method for quantitation of GR alpha isoform (GRalpha) expression
      using real-time PCR (qrt-PCR) with analytical capabilities to monitor patients,
      offering standard-curve reproducibility as well as intra- and inter-assay
      precision. RESULTS: Standard-curves were constructed by employing standardized
      Jurkat cell culture procedures, both for GRalpha and BCR (breakpoint cluster
      region), as a normalizing gene. We evaluated standard-curves using five different
      sets of cell culture passages, RNA extraction, reverse transcription, and qrt-PCR
      quantification. Intra-assay precision was evaluated using 12 replicates of each
      gene, for 2 patients, in a single experiment. Inter-assay precision was evaluated
      on 8 experiments, using duplicate tests of each gene for two patients. Standard
      curves were reproducible, with CV (coefficient of variation) of less than 11%,
      and Pearson correlation coefficients above 0,990 for most comparisons. Intra
      assay and inter-assay were 2% and 7%, respectively. CONCLUSION: This is the first
      method for quantitation of GRalpha expression with technical characteristics that
      permit patient monitoring, in a fast, simple and robust way.

PMID- 15507145
TI  - CLC-2 single nucleotide polymorphisms (SNPs) as potential modifiers of cystic
      fibrosis disease severity.
AB  - BACKGROUND: Cystic fibrosis (CF) lung disease manifest by impaired chloride
      secretion leads to eventual respiratory failure. Candidate genes that may modify
      CF lung disease severity include alternative chloride channels. The objectives of
      this study are to identify single nucleotide polymorphisms (SNPs) in the airway
      epithelial chloride channel, CLC-2, and correlate these polymorphisms with CF
      lung disease. METHODS: The CLC-2 promoter, intron 1 and exon 20 were examined for
      SNPs in adult CF dF508/dF508 homozygotes with mild and severe lung disease
      (forced expiratory volume at one second (FEV1) > 70% and < 40%). RESULTS: PCR
      amplification of genomic CLC-2 and sequence analysis revealed 1 polymorphism in
      the hClC -2 promoter, 4 in intron 1, and none in exon 20. Fisher's analysis
      within this data set, did not demonstrate a significant relationship between the
      severity of lung disease and SNPs in the CLC-2 gene. CONCLUSIONS: CLC-2 is not a
      key modifier gene of CF lung phenotype. Further studies evaluating other
      phenotypes associated with CF may be useful in the future to assess the ability
      of CLC-2 to modify CF disease severity.

PMID- 15507146
TI  - What is Nutrition & Metabolism?
AB  - A new Open Access journal, Nutrition & Metabolism (N&M) will publish articles
      that integrate nutrition with biochemistry and molecular biology. The open access
      process is chosen to provide rapid and accessible dissemination of new results
      and perspectives in a field that is of great current interest. Manuscripts in all
      areas of nutritional biochemistry will be considered but three areas of
      particular interest are lipoprotein metabolism, amino acids as metabolic signals,
      and the effect of macronutrient composition of diet on health. The need for the
      journal is identified in the epidemic of obesity, diabetes, dyslipidemias and
      related diseases, and a sudden increase in popular diets, as well as renewed
      interest in intermediary metabolism.

PMID- 15507147
TI  - Diet induced thermogenesis.
AB  - OBJECTIVE: Daily energy expenditure consists of three components: basal metabolic
      rate, diet-induced thermogenesis and the energy cost of physical activity. Here,
      data on diet-induced thermogenesis are reviewed in relation to measuring
      conditions and characteristics of the diet. METHODS: Measuring conditions include
      nutritional status of the subject, physical activity and duration of the
      observation. Diet characteristics are energy content and macronutrient
      composition. RESULTS: Most studies measure diet-induced thermogenesis as the
      increase in energy expenditure above basal metabolic rate. Generally, the
      hierarchy in macronutrient oxidation in the postprandial state is reflected
      similarly in diet-induced thermogenesis, with the sequence alcohol, protein,
      carbohydrate, and fat. A mixed diet consumed at energy balance results in a diet
      induced energy expenditure of 5 to 15 % of daily energy expenditure. Values are
      higher at a relatively high protein and alcohol consumption and lower at a high
      fat consumption. Protein induced thermogenesis has an important effect on
      satiety.In conclusion, the main determinants of diet-induced thermogenesis are
      the energy content and the protein- and alcohol fraction of the diet. Protein
      plays a key role in body weight regulation through satiety related to diet
      induced thermogenesis.

PMID- 15507148
TI  - Ketogenic diets and physical performance.
AB  - Impaired physical performance is a common but not obligate result of a low
      carbohydrate diet. Lessons from traditional Inuit culture indicate that time for
      adaptation, optimized sodium and potassium nutriture, and constraint of protein
      to 15-25 % of daily energy expenditure allow unimpaired endurance performance
      despite nutritional ketosis.

PMID- 15507149
TI  - beta3-adrenoceptor agonist prevents alterations of muscle diacylglycerol and
      adipose tissue phospholipids induced by a cafeteria diet.
AB  - BACKGROUND: Insulin resistance induced by a high fat diet has been associated
      with alterations in lipid content and composition in skeletal muscle and adipose
      tissue. Administration of beta3-adrenoceptor (beta3-AR) agonists was recently
      reported to prevent insulin resistance induced by a high fat diet, such as the
      cafeteria diet. The objective of the present study was to determine whether a
      selective beta3-AR agonist (ZD7114) could prevent alterations of the lipid
      profile of skeletal muscle and adipose tissue lipids induced by a cafeteria diet.
      METHODS: Male Sprague-Dawley rats fed a cafeteria diet were treated orally with
      either the beta3-AR agonist ZD7114 (1 mg/kg per day) or the vehicle for 60 days.
      Rats fed a chow diet were used as a reference group. In addition to the
      determination of body weight and insulin plasma level, lipid content and fatty
      acid composition in gastronemius and in epididymal adipose tissue were measured
      by gas-liquid chromatography, at the end of the study. RESULTS: In addition to
      higher body weights and plasma insulin concentrations, rats fed a cafeteria diet
      had greater triacylglycerol (TAG) and diacylglycerol (DAG) accumulation in
      skeletal muscle, contrary to animals fed a chow diet. As expected, ZD7114
      treatment prevented the excessive weight gain and hyperinsulinemia induced by the
      cafeteria diet. Furthermore, in ZD7114 treated rats, intramyocellular DAG levels
      were lower and the proportion of polyunsaturated fatty acids, particularly
      arachidonic acid, in adipose tissue phospholipids was higher than in animals fed
      a cafeteria diet. CONCLUSIONS: These results show that activation of the beta3-AR
      was able to prevent lipid alterations in muscle and adipose tissue associated
      with insulin resistance induced by the cafeteria diet. These changes in
      intramyocellular DAG levels and adipose tissue PL composition may contribute to
      the improved insulin sensitivity associated with beta3-AR activation.

PMID- 15507150
TI  - Virology on the Internet: the time is right for a new journal.
AB  - Virology Journal is an exclusively on-line, Open Access journal devoted to the
      presentation of high-quality original research concerning human, animal, plant,
      insect bacterial, and fungal viruses. Virology Journal will establish a strategic
      alternative to the traditional virology communication process.

PMID- 15507151
TI  - Amino acids as regulators of gene expression.
AB  - The role of amino acids as substrates for protein synthesis is well documented.
      However, a function for amino acids in modulating the signal transduction
      pathways that regulate mRNA translation has only recently been described.
      Interesting, some of the signaling pathways regulated by amino acids overlap with
      those classically associated with the cellular response to hormones such as
      insulin and insulin-like growth factors. The focus of this review is on the
      signaling pathways regulated by amino acids, with a particular emphasis on the
      branched-chain amino acid leucine, and the steps in mRNA translation controlled
      by the signaling pathways.

PMID- 15507153
TI  - Journal of Experimental & Clinical Assisted Reproduction: shaping the future of
      research and practice in reproductive endocrinology/infertility.
AB  - Journal of Experimental & Clinical Assisted Reproduction is an open access,
      online, peer-review journal publishing papers on all aspects of research into
      reproductive endocrinology, infertility, bioethics and the advanced reproductive
      technologies. The journal reports on important developments impacting the field
      of human reproductive medicine and surgery. The field exists as a sub-specialty
      of obstetrics & gynecology, focusing on the diagnosis and treatment of complex
      human reproductive problems. The continued growth of this relatively new field
      depends on quality research by proven scientists as well as junior investigators
      who, together, make contributions to this area of medical and surgical practice.
      The publishing revolution made possible by internet technology presages a bright
      future for continued interdisciplinary collaboration among researchers. Against
      this background, Journal of Experimental & Clinical Assisted Reproduction exists
      for the scientific community to facilitate this scholarly dialogue.

PMID- 15507152
TI  - Regulation of FeLV-945 by c-Myb binding and CBP recruitment to the LTR.
AB  - BACKGROUND: Feline leukemia virus (FeLV) induces degenerative, proliferative and
      malignant hematologic disorders in its natural host, the domestic cat. FeLV-945
      is a viral variant identified as predominant in a cohort of naturally infected
      animals. FeLV-945 contains a unique sequence motif in the long terminal repeat
      (LTR) comprised of a single copy of transcriptional enhancer followed by a 21-bp
      sequence triplicated in tandem. The LTR is precisely conserved among independent
      cases of multicentric lymphoma, myeloproliferative disease and anemia in animals
      from the cohort. The 21-bp triplication was previously shown to act as a
      transcriptional enhancer preferentially in hematopoietic cells and to confer a
      replicative advantage. The objective of the present study was to examine the
      molecular mechanism by which the 21-bp triplication exerts its influence and the
      selective advantage responsible for its precise conservation. RESULTS: Potential
      binding sites for the transcription factor, c-Myb, were identified across the
      repeat junctions of the 21-bp triplication. Such sites would not occur in the
      absence of the repeat; thus, a requirement for c-Myb binding to the repeat
      junctions of the triplication would exert a selective pressure to conserve its
      sequence precisely. Electrophoretic mobility shift assays demonstrated specific
      binding of c-Myb to the 21-bp triplication. Reporter gene assays showed that the
      triplication-containing LTR is responsive to c-Myb, and that responsiveness
      requires the presence of both c-Myb binding sites. Results further indicated that
      c-Myb in complex with the 21-bp triplication recruits the transcriptional co
      activator, CBP, a regulator of normal hematopoiesis. FeLV-945 replication was
      shown to be positively regulated by CBP in a manner dependent on the presence of
      the 21-bp triplication. CONCLUSION: Binding sites for c-Myb across the repeat
      junctions of the 21-bp triplication may account for its precise conservation in
      the FeLV-945 LTR. c-Myb binding and CBP recruitment to the LTR positively
      regulated virus production, and thus may be responsible for the replicative
      advantage conferred by the 21-bp triplication. Considering that CBP is present in
      hematopoietic cells in limiting amounts, we hypothesize that FeLV-945 replication
      in bone marrow may influence CBP availability and thereby alter the regulation of
      CBP-responsive genes, thus contributing to altered hematopoiesis and consequent
      hematologic disease.

PMID- 15507155
TI  - Lead editorial: The need for greater perspective and innovation in epidemiology.
AB  - This editorial introduces the new online, open-access, peer-reviewed journal,
      Epidemiologic Perspectives & Innovations. Epidemiology (which we define broadly,
      to include clinical research and various approaches to studying the health of
      populations) is a critically important field in informing decisions about the
      health of individuals and populations. But the desire for new information means
      that the health science literature is overwhelmingly devoted to reporting new
      findings, leaving little opportunity to improve the quality of the science. By
      creating a journal dedicated to all topics of and about epidemiology, except
      standard research reports, we hope to encourage authors to write more on the
      neglected aspects of the field. The journal will publish articles that analyze
      policy implications of health research, present new research methods and better
      communicate existing methods, reassess previous results and dogma, and provide
      other innovations in and perspectives on the field. Online publishing will permit
      articles of whatever length is required for the work, speed the time to
      publication and allow free access to the full content.

PMID- 15507154
TI  - Genetically distant American Canine distemper virus lineages have recently caused
      epizootics with somewhat different characteristics in raccoons living around a
      large suburban zoo in the USA.
AB  - BACKGROUND: Mortality rates have differed during distemper outbreaks among free
      ranging raccoons (Procyon lotor) living around a large Chicago-area zoo, and
      appeared higher in year 2001 than in 1998 and 2000. We hypothesized that a more
      lethal variant of the local Canine distemper virus (CDV) lineage had emerged in
      2001, and sought the genetic basis that led to increased virulence. However, a
      more complex model surfaced during preliminary analyses of CDV genomic sequences
      in infected tissues and of virus isolated in vitro from the raccoons. RESULTS:
      Phylogenetic analyses of subgenomic CDV fusion (F) -, phosphoprotein (P) -, and
      complete hemagglutinin (H) - gene sequences indicated that distinct American CDV
      lineages caused the distemper epizootics. The 1998 outbreak was caused by viruses
      that are likely from an old CDV lineage that includes CDV Snyder Hill and
      Lederle, which are CDV strains from the early 1950's. The 2000 and 2001 viruses
      appear to stem from the lineage of CDV A75/17, which was isolated in the mid
      1970's. Only the 2001 viruses formed large syncytia in brain and/or lung tissue,
      and during primary isolation in-vitro in Vero cells, demonstrating at least one
      phenotypic property by which they differed from the other viruses. CONCLUSIONS:
      Two different American CDV lineages caused the raccoon distemper outbreaks. The
      1998 viruses are genetically distant to the 2000/2001 viruses. Since CDV does not
      cause persistent infections, the cycling of different CDV lineages within the
      same locale suggests multiple reintroductions of the virus to area raccoons. Our
      findings establish a precedent for determining whether the perceived differences
      in mortality rates are actual and attributable in part to inherent differences
      between CDV strains arising from different CDV lineages.

PMID- 15507156
TI  - Editorial: Wishful thinking.
AB  - As a supplement to our lead editorial, the editors of the new journal,
      Epidemiologic Perspectives & Innovations, provide a partial list of specific
      analyses and topic areas they would like to see submitted to the journal.

PMID- 15507157
TI  - Metabolic response of people with type 2 diabetes to a high protein diet.
AB  - BACKGROUND: One of the major interests in our laboratory has been to develop a
      scientific framework for dietary advice for patients with diabetes. Knowledge
      regarding the metabolic consequences and potential effects on health of protein
      in people with type 2 diabetes has been a particular interest. RESULTS: We
      recently have completed a study in which dietary protein was increased from 15%
      to 30% of total food energy. The carbohydrate content was decreased from 55% to
      40%, i.e. dietary protein replaced part of the carbohydrate. This resulted in a
      significant decrease in total glycohemoglobin, a decrease in postprandial glucose
      concentrations and a modest increase in insulin concentration. Renal function was
      unchanged. Currently we also are determining the metabolic response to a diet in
      which the carbohydrate content is further decreased to 20% of total food energy.
      The %tGHb decrease was even more dramatic than with the 40% carbohydrate diet.
      CONCLUSION: From these data we conclude that increasing the protein content of
      the diet at the expense of carbohydrate can reduce the 24-hour integrated plasma
      glucose concentration, at least over a 5-week period of time. The reduction was
      similar to that of oral agents. Renal function was not affected significantly.
      Thus, increasing the protein content of the diet with a corresponding decrease in
      the carbohydrate content potentially is a patient empowering way of reducing the
      hyperglycemia present with type 2 diabetes mellitus, independent of the use of
      pharmaceutical agents.

PMID- 15507158
TI  - A knowledgebase system to enhance scientific discovery: Telemakus.
AB  - BACKGROUND: With the rapid expansion of scientific research, the ability to
      effectively find or integrate new domain knowledge in the sciences is proving
      increasingly difficult. Efforts to improve and speed up scientific discovery are
      being explored on a number of fronts. However, much of this work is based on
      traditional search and retrieval approaches and the bibliographic citation
      presentation format remains unchanged. METHODS: Case study. RESULTS: The
      Telemakus KnowledgeBase System provides flexible new tools for creating
      knowledgebases to facilitate retrieval and review of scientific research reports.
      In formalizing the representation of the research methods and results of
      scientific reports, Telemakus offers a potential strategy to enhance the
      scientific discovery process. While other research has demonstrated that
      aggregating and analyzing research findings across domains augments knowledge
      discovery, the Telemakus system is unique in combining document surrogates with
      interactive concept maps of linked relationships across groups of research
      reports. CONCLUSION: Based on how scientists conduct research and read the
      literature, the Telemakus KnowledgeBase System brings together three innovations
      in analyzing, displaying and summarizing research reports across a domain: (1)
      research report schema, a document surrogate of extracted research methods and
      findings presented in a consistent and structured schema format which mimics the
      research process itself and provides a high-level surrogate to facilitate
      searching and rapid review of retrieved documents; (2) research findings, used to
      index the documents, allowing searchers to request, for example, research studies
      which have studied the relationship between neoplasms and vitamin E; and (3)
      visual exploration interface of linked relationships for interactive querying of
      research findings across the knowledgebase and graphical displays of what is
      known as well as, through gaps in the map, what is yet to be tested. The
      rationale and system architecture are described and plans for the future are
      discussed.

PMID- 15507159
TI  - True good.

PMID- 15507160
TI  - Comparisons of the M1 genome segments and encoded mu2 proteins of different
      reovirus isolates.
AB  - BACKGROUND: The reovirus M1 genome segment encodes the mu2 protein, a
      structurally minor component of the viral core, which has been identified as a
      transcriptase cofactor, nucleoside and RNA triphosphatase, and microtubule
      binding protein. The mu2 protein is the most poorly understood of the reovirus
      structural proteins. Genome segment sequences have been reported for 9 of the 10
      genome segments for the 3 prototypic reoviruses type 1 Lang (T1L), type 2 Jones
      (T2J), and type 3 Dearing (T3D), but the M1 genome segment sequences for only T1L
      and T3D have been previously reported. For this study, we determined the M1
      nucleotide and deduced mu2 amino acid sequences for T2J, nine other reovirus
      field isolates, and various T3D plaque-isolated clones from different
      laboratories. RESULTS: Determination of the T2J M1 sequence completes the
      analysis of all ten genome segments of that prototype. The T2J M1 sequence
      contained a 1 base pair deletion in the 3' non-translated region, compared to the
      T1L and T3D M1 sequences. The T2J M1 gene showed approximately 80% nucleotide
      homology, and the encoded mu 2 protein showed approximately 71% amino acid
      identity, with the T1L and T3D M1 and mu2 sequences, respectively, making the T2J
      M1 gene and mu2 proteins amongst the most divergent of all reovirus genes and
      proteins. Comparisons of these newly determined M1 and mu2 sequences with newly
      determined M1 and mu2 sequences from nine additional field isolates and a variety
      of laboratory T3D clones identified conserved features and/or regions that
      provide clues about mu2 structure and function. CONCLUSIONS: The findings suggest
      a model for the domain organization of mu2 and provide further evidence for a
      role of mu2 in viral RNA synthesis. The new sequences were also used to explore
      the basis for M1/mu2-determined differences in the morphology of viral factories
      in infected cells. The findings confirm the key role of Ser/Pro208 as a prevalent
      determinant of differences in factory morphology among reovirus isolates and
      trace the divergence of this residue and its associated phenotype among the
      different laboratory-specific clones of type 3 Dearing.

PMID- 15507161
TI  - Metabolic aspects of low carbohydrate diets and exercise.
AB  - Following a low carbohydrate diet, there is a shift towards more fat and less
      carbohydrate oxidation to provide energy to skeletal muscle, both at rest and
      during exercise. This review summarizes recent work on human skeletal muscle
      carbohydrate and fat metabolic adaptations to a low carbohydrate diet, focusing
      mainly on pyruvate dehydrogenase and pyruvate dehydrogenase kinase, and how these
      changes relate to the capacity for carbohydrate oxidation during exercise.

PMID- 15507162
TI  - Consumer-directed health care: are consumers ready?

PMID- 15507163
TI  - Expanding opportunities for handheld technology use in respiratory care.

PMID- 15507164
TI  - Impact of a program to provide patients with comparative information about
      providers of durable medical equipment for home respiratory care.
AB  - BACKGROUND: How patients are informed regarding their choices of durable medical
      equipment (DME) providers for home-going respiratory equipment may affect their
      decisions about which vendor to use. When a new enhanced information program to
      inform home-going patients about all available respiratory DME providers was
      implemented, we hypothesized that patients' utilization of providers would change
      and that satisfaction with service would be enhanced. METHODS: The enhanced
      information program consisted of offering detailed descriptions of the many
      available providers to home-going patients. To characterize available providers,
      we administered a questionnaire to all respiratory DME providers listed in our
      area. We assembled information about the scope of services, the number and types
      of providers, the geographic range of service, and the providers' contact
      information, on a 1-page information sheet about the DME providers, which was
      given to all home-going patients. Case managers, who routinely help patients make
      such DME arrangements, were oriented about the questionnaire and given the
      information sheets to distribute. The study compared responses from Medicare
      insurees prescribed to receive home-going respiratory care equipment on discharge
      from The Cleveland Clinic Hospital during the periods before and after
      implementing the enhanced information program. Consecutive eligible patients in
      the before and after groups were called by two of the study investigators (ERH,
      DAM), at least 2 weeks after discharge, and, on their granting consent, were
      asked to complete a telephone survey. RESULTS: Responses were available from 75
      patients in each group. Both before and after implementing the enhanced
      information program, patients' satisfaction with their respiratory DME service
      providers' services was high. The number of providers selected increased after
      the program from 12 to 18, and though the differences between the before and
      after scores were not statistically significant, there was a trend toward
      prompter visits to patients in their homes by DME-provider respiratory
      therapists. CONCLUSIONS: The enhanced information program was associated with a
      larger number of DME providers being selected, with preservation of a high level
      of patient satisfaction with DME services. The trend toward prompter respiratory
      therapists' visits to the home and better availability of oxygen canisters for at
      home patients suggested benefits from the enhanced information program.

PMID- 15507165
TI  - Are blood gases necessary in mechanically ventilated patients who have
      successfully completed a spontaneous breathing trial?
AB  - BACKGROUND: The utility of routinely obtaining arterial blood gas analyses (ABGs)
      prior to extubation in patients who have successfully completed a spontaneous
      breathing trial is not known. OBJECTIVE: Review our practices and determine our
      extubation success rate with a policy of selective ABG utilization. METHODS:
      Retrospective chart review. RESULTS: We reviewed 54 extubations of 52 patients.
      Sixty-five percent of the extubations were performed without obtaining an ABG
      after the spontaneous breathing trial. The extubation success rate was 94% for
      the entire group and was the same regardless of whether an ABG measurement was
      obtained (94.7% vs 94.3%, respectively). CONCLUSION: ABG measurement does not
      appear to be a prerequisite to extubation following a clinically successful
      spontaneous breathing trial.

PMID- 15507166
TI  - The effect of body mass index on outcomes of patients receiving noninvasive
      positive-pressure ventilation in acute respiratory failure.
AB  - BACKGROUND: A study was undertaken to determine factors present in adult
      patients, newly admitted to the hospital, that predict the inability of
      noninvasive positive-pressure ventilation (NPPV) to sustain the work of breathing
      and avoid endotracheal intubation. METHODS: Data were collected prospectively
      from patients with acute respiratory failure who were admitted to Hackensack
      University Medical Center from August 2001 to August 2002 and received NPPV.
      Physiologic characteristics of those patients on admission were compiled into a
      database, with the hypothesis that those with the worst initial physiologic
      characteristics would subsequently fail NPPV and require endotracheal intubation
      with mechanical ventilation. RESULTS: Seventy-five patients were included. Sixty
      four patients (85%) successfully avoided endotracheal intubation and were
      discharged. Of the 11 patients who failed NPPV, 8 were intubated and 5 expired.
      The groups were comparable in age, sex, arterial blood gases, and Acute
      Physiology and Chronic Health Evaluation score (p > 0.05). The success group,
      however, had a significantly higher body mass index (29 kg/m(2) vs 23 kg/m(2), p
      = 0.0167). CONCLUSIONS: The following can be concluded from our study: there is a
      low failure rate for NPPV (15%); patients with a low body mass index are more
      likely to fail NPPV and require endotracheal intubation; and patients who fail
      NPPV have a higher risk of mortality (p = 0.00016).

PMID- 15507167
TI  - Determinants of dynamic hyperinflation in a bench model.
AB  - BACKGROUND: Previous in vivo data suggest that high airway resistance (R(aw))
      promotes dynamic hyperinflation, especially when coupled to high minute
      ventilation (V(E)). However, no studies have systematically examined the relative
      effects of various mechanical parameters on dynamic hyperinflation. METHODS:
      Intrinsic positive end-expiratory pressure (PEEPi) was measured with a ventilator
      lung model, over a range and various permutations of R(aw), V(E), respiratory
      system compliance (C(RS)), and duty cycles/flow regimes. RESULTS: Substantial
      dynamic hyperinflation (PEEPi > 5 cm H(2)O occurred at various V(E), even when
      R(aw) was low (4 cm H(2)O/L/s) or just above normal (18 cm H(2)O/L/s). A V(E) >
      or = 15 L/min was associated with increasing PEEPi in this model, across a broad
      range of mechanical permutations. PEEPi was significantly higher in all models
      during descending ramp flow than during constant flow, at equivalent peak flows
      (wherein duty cycle during descending ramp flow was twice that of constant flow).
      PEEPi was equivalent when duty cycles (and all other mechanical parameters) were
      equal. PEEPi was significantly greater, irrespective of duty cycle, R(aw), and
      C(RS), when delivered with lower tidal volume (0.6 L vs 1.0 L). The change in
      peak airway pressure associated with development of dynamic hyperinflation was
      consistently greater than the observed PEEPi. Higher V(E), resistance,
      compliance, and duty cycles were all independently associated with dynamic
      hyperinflation. CONCLUSIONS: In this bench model, dynamic hyperinflation occurred
      with high V(E), even at low R(aw). Since moderate R(aw) and V(E) frequently occur
      in vivo, even without obstructive lung disease, occult dynamic hyperinflation is
      likely to occur commonly. PEEPi was greater with high frequency and small tidal
      volume (0.6 L) than with equal V(E) of lower frequency and larger tidal volume
      (1.0 L).

PMID- 15507168
TI  - Pulmonary hyperinflation and respiratory distress following solvent aspiration in
      a patient with asthma: expectoration of bronchial casts and clinical improvement
      with high-frequency chest wall oscillation.
AB  - An 18-year-old student with a history of asthma accidentally inhaled organic
      solvent during a class, with immediate cough and dyspnea that worsened over
      several hours. He presented in severe respiratory distress, with hypoxemia and
      marked pulmonary hyperinflation. Administration of inhaled bronchodilator was
      ineffective because of agitation, and the patient could not be positioned for
      chest physiotherapy to treat presumed widespread mucus plugging. High-frequency
      chest wall oscillation (HFCWO) in the sitting position initially caused increased
      distress but was subsequently tolerated when noninvasive positive-pressure
      ventilation (NPPV) via nasal mask was initiated. Almost immediately, the patient
      began expectorating bronchial mucus casts, with concomitant clinical improvement.
      Endotracheal intubation was avoided, and with aggressive pharmacologic treatment
      for acute severe asthma and continuation of intermittent HFCWO-NPPV, the patient
      made a full recovery over the next several days. This case suggests that the
      combination of HFCWO and NPPV may be helpful in the presence of mucus plugging as
      a complication of acute inhalation injury or acute severe asthma.

PMID- 15507169
TI  - Respiratory care billing using a personal digital assistant.
AB  - In 2003 I reported how my respiratory care department at Tufts-New England
      Medical Center developed an inexpensive, in-house, computerized clinical
      information-management system, in which the respiratory therapists carry handheld
      computers during their rounds, entering clinical information into the handhelds
      as they work and later downloading that information to a database in a desktop
      computer. Now we have added a billing module to our customized software. This
      article describes the design, use, and attributes of this billing system,
      including improved charge-capture, which increased department revenue
      substantially. Our system has several other important advantages over traditional
      billing systems.

PMID- 15507170
TI  - Breast cancer surveillance in women with hereditary risk due to BRCA1 or BRCA2
      mutations.
AB  - Women with germline mutations in BRCA1 or BRCA2 are known to be at substantially
      elevated risk for breast cancer. With increasing acceptance of genetic testing,
      significant numbers of mutation carriers are being identified, but evidence-based
      guidelines for the management of women at hereditary risk are lacking. This
      article reviews the most commonly recommended modalities employed in breast
      cancer surveillance for women at increased risk. It is apparent that the standard
      techniques of breast self-examination, clinical breast examination, and
      mammography are suboptimal for the identification of hereditary breast cancer. At
      least half of the cancers in this population appear to be detected by physical
      examination in the intervals between routine radiographic surveillance. Host
      factors (eg, breast density) and tumor features (rapid proliferative rates)
      likely contribute to the relative insensitivity of mammography. These factors may
      be mitigated by the deployment of screening techniques for breast cancer such as
      ultrasound and magnetic resonance imaging. However, the effect of incremental
      screening on either stage at diagnosis or breast cancer mortality has not been
      defined. In addition, the impact of the relatively limited specificity of these
      techniques on the quality of life (QOL) of women at risk has not been studied.
      Further research is needed to evaluate the effect of incremental radiographic
      screening on outcomes, to delineate the best way to integrate the different
      modalities in terms of sequencing and frequency, and to identify interventions
      that will minimize the impact of intensive surveillance programs on the QOL of
      the women engaged in them.

PMID- 15507173
TI  - Internal mammary node drainage and its role in sentinel lymph node biopsy: the
      initial ALMANAC experience.
AB  - This study was designed to identify the frequency of internal mammary drainage in
      patients undergoing sentinel lymph node (SLN) lymphoscintigraphy in a controlled
      clinical trial. The practicability and relevance of internal mammary SLN biopsy
      as a method to improve nodal staging and treatment in breast cancer were
      investigated. A total of 707 evaluable patients with invasive breast cancer
      underwent SLN biopsy based on lymphoscintigraphy, intraoperative g probe
      detection, and blue dye mapping using technetium Tc 99m albumin colloid and
      Patent Blue V injected peritumorally. This was followed by standard axillary
      treatment in the same operation in all patients. Lymphoscintigraphy showed
      internal mammary sentinel nodes in 62 patients (9%), and internal mammary
      drainage was identified perioperatively in an additional 7 patients (1%) using g
      probe detection. Sampling of the internal mammary basin, based on the results of
      lymphoscintigraphy and g probe detection, was done in 31 of 69 patients (45%).
      One patient had a pneumothorax and 2 experienced bleeding during internal mammary
      sampling. Internal mammary metastases were detected in 4 of 31 patients (13%). In
      2 of the patients (6%), internal mammary nodes (IMNs) showed metastatic
      involvement without accompanying axillary metastases. One of these 2 patients
      would have received adjuvant endocrine systemic therapy because of the
      characteristics of the tumor, but may not have been recommended to receive
      adjuvant chemotherapy. Sampling of the internal mammary basin led to a change of
      management in these 2 patients, ie, institution of adjuvant chemotherapy.
      Therefore, a change in management occurred in only 2 of the 69 patients in our
      series, but 38 patients with unbiopsied "hot" IMNs remained with unknown internal
      mammary status. Biopsy of IMNs alters staging in few patients, and the impact on
      indication for adjuvant treatment was low. Internal mammary SLN biopsy may be
      associated with some additional morbidity. Current evidence suggests that
      internal mammary SLN biopsy is still a research tool.

PMID- 15507172
TI  - Survival benefit with capecitabine/docetaxel versus docetaxel alone: analysis of
      therapy in a randomized phase III trial.
AB  - In a large phase III trial of 511 patients with anthracycline-pretreated
      advanced/metastatic breast cancer, capecitabine/docetaxel combination therapy was
      shown to have significantly superior efficacy compared with single-agent
      docetaxel, including superior progression-free and overall survival and objective
      response rate. An updated survival analysis with >/= 27 months follow-up shows
      that patients receiving combination therapy maintained significantly superior
      survival (hazard ratio [HR], 0.777 [95% CI, 0.645-0.942]; P < 0.01; median
      survival, 14.5 months vs. 11.5 months) compared with those receiving single-agent
      docetaxel. Following the failure of docetaxel monotherapy, 35% of patients did
      not receive additional cytotoxic chemotherapy. Among patients randomized to
      single-agent docetaxel, only those given poststudy single-agent capecitabine had
      significantly prolonged survival compared with those given any other poststudy
      chemotherapy (HR, 0.500; P = 0.0046; median survival, 21.0 months vs. 12.3
      months, respectively). By contrast, poststudy vinorelbine-containing chemotherapy
      did not affect survival following progression on single-agent docetaxel compared
      with other poststudy chemotherapy regimens (HR, 1.014; P = 0.94; median survival,
      13.5 months vs. 12.6 months, respectively). Among patients randomized to
      combination therapy, discontinuing docetaxel of capecitabine has a similar effect
      on survival (HR, 0.720; P = 0.20; median survival, 15.8 months vs. 18.3 months,
      respectively). Median survival was 18.3 months in patients who discontinued
      docetaxel and continued to receive capecitabine versus 15.8 months in patients
      who discontinued capecitabine and continued to receive docetaxel, with a trend
      toward improved survival in patients continuing to receive capecitabine. Although
      this is a retrospective analysis, these data suggest that the sequential
      administration of docetaxel followed by capecitabine is associated with prolonged
      survival in patients who are candidates for sequential single-agent therapy.

PMID- 15507175
TI  - Final results of a phase II clinical trial of weekly docetaxel in combination
      with capecitabine in anthracycline-pretreated metastatic breast cancer.
AB  - The addition of capecitabine to docetaxel on a 3-week schedule resulted in
      superior response rate, increased time to progression (TTP), and improved overall
      survival in patients with anthracycline-pretreated metastatic breast cancer
      (MBC). Because the toxicity profile of weekly docetaxel differs from the standard
      21-day docetaxel schedule, we performed a phase I/II trial to test the efficacy
      and safety of weekly docetaxel in combination with capecitabine given for 14 days
      every 21 days. The phase I study identified the doses of docetaxel (30 mg/m2
      weekly) and capecitabine (900 mg/m2 twice daily on days 1-14 every 21 days) used
      in phase II. Twenty female patients with measurable or assessable MBC were
      enrolled. Eighteen patients had previously received anthracyclines; 2 had
      contraindications to anthracyclines. Patients remained on study for a maximum of
      eight 3-week cycles or until tumor progression or unacceptable toxicity occurred;
      response assessments were scheduled after cycle 2, 5, and 8. Seventeen patients
      were assessed after cycle 2; 3 subjects (18%) had a partial response (PR), 9 had
      stable disease (53%; SD), and 5 patients (29%) had progressive disease (PD). Ten
      patients were assessable after cycle 5. Two patients (20%) had a PR, 5 patients
      (50%) had SD, and 3 patients (30%) had PD. The most common grade 3 toxicities
      were nail loss (45%), asthenia (30%), and hand-foot syndrome (30%), and
      toxicities led to study discontinuation in 10 patients. The median time to
      treatment failure was 10 weeks and median TTP was 26 weeks. The median duration
      of response was 9 weeks and the median duration of SD was 16 weeks. The median
      overall survival was 82 weeks. This schedule of weekly docetaxel in combination
      with day 1-14 capecitabine has activity; however, toxicity discourages the use of
      this schedule in lieu of the standard docetaxel/capecitabine regimen.

PMID- 15507176
TI  - Effect of cardiac dysfunction on treatment outcomes in women receiving
      trastuzumab for HER2-overexpressing metastatic breast cancer.
AB  - Trastuzumab improves time to disease progression (TTP) and survival when added to
      chemotherapy for HER-positive metastatic breast cancer (MBC), but it is
      associated with infrequent cardiac dysfunction (CD). We analyzed data from a
      previous pivotal randomized trial of 469 women with HER2-overexpressing MBC. The
      aim was to determine the benefit of adding trastuzumab to chemotherapy in terms
      of TTP that was free of CD, including all CD, moderate or severe (New York Heart
      Association class III/IV) CD only, or moderate or severe CD that did not improve
      with cardiac therapy. We also assessed moderate or severe CD-free survival. We
      assessed the impact of trastuzumab for these indices on the entire cohort and on
      specific chemotherapy subsets. Median TTP or any CD improved when trastuzumab was
      added to all chemotherapy (4.6 months vs. 6.6 months with trastuzumab, P =
      0.0001), an anthracycline (doxorubicin or epirubicin) plus cyclophosphamide (AC;
      6.0 months vs. 6.6 months, P = 0.24), and paclitaxel (2.8 months vs. 6.6 months,
      P = 0.0001). When defined as time to moderate or severe CD, median TTP improved
      when trastuzumab was added to all chemotherapy (4.6 months vs. 7.0 months, P =
      0.0001), AC (6.0 months vs. 7.2 months, P = 0.02), and paclitaxel (2.8 months vs.
      6.9 months, P = 0.0001). There was no statistical difference between moderate and
      severe CD-free survival with trastuzumab added to chemotherapy. Outcomes improved
      with trastuzumab despite CD. In particular, the benefit from
      trastuzumab/paclitaxel outweighed the potential risk of CD in patients with MBC.
      These types of analyses will be critical for trials assessing trastuzumab as
      adjuvant therapy.

PMID- 15507177
TI  - Ductal lavage using medically aseptic technique in women at high risk for breast
      cancer.
AB  - Ductal lavage of the breast is a minimally invasive procedure used to collect
      epithelial cells from the lumen of the ductolobular system for cytologic
      analysis. The purpose of this study was to determine the safety of using an
      aseptic technique in performing ductal lavage. The study included 114 consecutive
      patients at high risk for breast cancer with clinically negative mammograms and
      no palpable masses. Ductal lavage could not be performed on 32 of the 114
      patients (28%): 26 because nipple aspirate fluid could not be obtained, and 6
      because a fluid-yielding duct could not be cannulated. Ductal lavage was
      successfully performed on 82 patients (72%). Local anesthetic cream was used on
      the nipple area and local anesthetic was infused into each duct. The nipple, the
      cup of the nipple aspirator device, and any dilator tools were cleansed with
      alcohol before use. Separate sterile microcatheters were used for each duct.
      Sterile saline solution was used for the infusions. No patient reported any
      symptoms indicating infection after lavage. Cytologic analysis from the 82 lavage
      cases showed 45 benign cells (55%), 17 cases of mild atypia (21%), 1 case of
      marked atypia, and 1 case with malignant cells. Eighteen samples (22%) had
      inadequate cellularity for medical diagnosis. The results of the study indicate
      that an aseptic technique is safe and appropriate for ductal lavage of the
      breast.

PMID- 15507179
TI  - Selection criteria for accelerated partial-breast irradiation: impact on
      applicability.
AB  - This study examines the potential applicability of accelerated partial-breast
      irradiation (APBI) based on clinical and pathologic selection criteria in
      patients with stage I/II breast cancer. The records of 535 patients treated with
      breast-conserving surgery and radiation were reviewed. The patient database was
      analyzed for the following factors: age, extensive intraductal carcinoma (EIC),
      lymphovascular invasion (LVI), margin status, histologic type, pathologic nodal
      status, and pathologic tumor size. Two hundred seventeen records were located.
      The minimal selection criteria for APBI were assumed to include patient age of
      >/= 45 years, nonlobular histology, negative margins (> 2 mm), absence of EIC,
      and node-negative status. The potential variations in selection criteria for age,
      tumor size, and LVI were investigated with regard to the proportion of patients
      who would be eligible for APBI. In addition, predictors for true versus diffuse
      recurrence were examined among 40 patients who had a local recurrence. Using
      variable patient age cutoffs and T2 tumors as well as LVI, 9%-47% of patients
      could have been considered for APBI in this study. Using an age cutoff of >/= 65
      years, 9%-15% of patients could have been eligible for APBI. However, using an
      age cutoff of >/=45 years, 28%-47% might be eligible, with the consideration of
      LVI becoming important. Among 40 local recurrences, 12 occurred at the primary
      site; 15 occurred elsewhere, diffusely, or with dermal involvement; and the
      locations of 13 could not be determined. Extensive intraductal carcinoma was the
      only significant predictor for recurrence at the primary site (P = 0.01). The
      potential impact of APBI on breast radiation therapy practice needs to be further
      delineated, and appropriate selection criteria should be refined.

PMID- 15507178
TI  - Neoadjuvant FEC 100 for operable breast cancer: eight-year experience at Centre
      Jean Perrin.
AB  - This study investigated the efficacy and tolerability of FEC 100 (epirubicin 100
      mg/m2 with 5-fluorouracil 500 mg/m2 and cyclophosphamide 500 mg/m2) every 21 days
      as neoadjuvant chemotherapy in women with stage I-III primary operable breast
      cancer. Forty patients were treated with 6 cycles of FEC 100, followed by surgery
      and radiation therapy. In addition, most patients also received an adjuvant
      treatment for residual disease (11 chemotherapies and 31 tamoxifen). After 6
      cycles of FEC 100, the overall clinical response rate of 75% (CI 95%, 61.6-88.4)
      was achieved, 22.5% of which were complete responses. Breast conservation was
      achieved in 70% of patients. A pathologic complete response was confirmed in 6
      patients (15%; CI 95%, 3.9-26.1) using Chevallier's classification and in 10
      patients (25%; CI 95%, 11.6-38.4) using Sataloff's classification. After a median
      follow-up of 29.5 months, 3 metastatic relapses were observed. The principal
      toxicity of FEC 100 was myelosuppression; 51.3% of patients developed grade 3/4
      neutropenia. Neoadjuvant FEC 100 was both effective and well tolerated in
      patients with early-stage operable breast cancer.

PMID- 15507180
TI  - A method for making estimates of the benefit of the late use of letrozole in
      patients completing 5 years of tamoxifen.
AB  - This article discusses the rationale for 2 methods of making estimates of the
      benefit of letrozole as extended adjuvant hormonal therapy after 5 years of
      tamoxifen. It uses information from the Overview metaanalyses to develop general
      rules for making estimates of remaining risk of relapse for women completing 5
      years of adjuvant tamoxifen without relapse. The first derived method shows that
      the expected benefit for such a woman is approximately one tenth of her risk of
      relapse in years 0-10 if untreated. The second method uses a modification of
      Adjuvant!, a decision support tool, and makes similar estimates. The decision
      tool supplies needed estimates of initial risk and allows adjustment for
      competing mortality. Uncertainties involved in making these estimates are also
      discussed.

PMID- 15507181
TI  - Paclitaxel chemotherapy in a pregnant patient with bilateral breast cancer.
AB  - In this article, we report on a case of a pregnant patient with synchronous
      bilateral breast cancer treated with weekly paclitaxel. She presented after right
      mastectomy and anthracycline-based chemotherapy at an outside facility. Staging
      studies at our hospital before taxane administration demonstrated a 19-20-week
      gravid uterus and tumor in the remaining left breast. Weekly paclitaxel was given
      preoperatively during pregnancy. A normal male infant was delivered. Upon
      completion of chemotherapy, the patient underwent mastectomy and axillary lymph
      node dissection followed by comprehensive radiation therapy to the chest wall.

PMID- 15507182
TI  - [Is there a link between continuous quality improvement programs and health
      service users' satisfaction with prenatal care? An experience in Peruvian
      hospitals].
AB  - OBJECTIVES: 1. To compare the level of health service user satisfaction (US) with
      antenatal care in hospitals where a program of continuous quality improvement
      (CQI) was implemented, in comparison to a reference group of patients seen at
      hospitals that did not participate in the program. 2. To compare the reasons for
      dissatisfaction in both groups of users. 3. To identify the factors associated
      with US. METHODS: A quasi-experimental study of a representative sample of
      pregnant women attending prenatal care services. The women in the intervention
      group (n = 191) and the reference group (n = 185) were interviewed on leaving the
      prenatal care clinic. The dependent variable was satisfaction with prenatal care,
      and the independent variables were satisfaction of expectations, amiability,
      level of health information, perception of the equipment, waiting time,
      cleanliness and comfort. Descriptive and multivariate statistics were calculated.
      RESULTS: The intervention group showed higher rates of US (67.5% versus 55.1% in
      the reference group, P = 0.014). The main reasons for dissatisfaction were long
      waiting times and discourteous treatment, which were more frequent in the
      reference group. The multivariate analysis identified cordiality of the health
      professionals, information provided during the visit, satisfaction of
      expectations and implementation of the CQI program as the factors that were
      significantly associated with US. CONCLUSIONS: Our findings show that the CQI
      program in maternal and perinatal health services was positively associated with
      US. These results reinforce the need for cordiality during prenatal care contacts
      with providers, and the need to provide appropriate information to the user, in
      order to help increase acceptability of and adhesion to health care
      recommendations among pregnant women.

PMID- 15507183
TI  - Vaccination coverage among children aged 13 to 59 months in Buenos Aires,
      Argentina, 2002.
AB  - OBJECTIVES: To estimate antigen-specific and series-complete vaccination coverage
      among children aged 13 to 59 months in Buenos Aires; to compare the results of a
      community-based household survey with coverage rates obtained from administrative
      records; and to identify risk factors for incomplete vaccination. METHODS: Census
      tracts in Buenos Aires were surveyed systematically in March and April, 2002.
      Three children aged 13 to 24 months and 25 to 59 months were surveyed per block
      in each census tract. Written documentation of vaccination was required. Risk
      factors associated with incomplete vaccination were identified with univariate
      analysis and multivariate logistic regression. RESULTS: A total of 1391 children
      were surveyed. Antigen-specific coverage ranged from 69.4% (95% CI 66.7%-72%) for
      Haemophilus influenzae type b vaccination to 99% (95% CI 98.4%-99.6%) for BCG
      vaccination. Except for measles, coverage estimates found in the survey did not
      differ substantially from those obtained from city health authority records.
      Multivariate logistic regression analysis showed child's age (P < 0.001) and
      vaccination provider (public or private) (P = 0.001) to be risk factors
      associated with incomplete vaccination. Not being the first child (P < 0.001) was
      associated with incomplete coverage under the long-standing program. Living in
      the Northern zone of the city (P = 0.001), being uninsured (P = 0.02), and lower
      educational level of the primary caregiver (P = 0.04) were risk factors
      associated with incomplete coverage under the current vaccination program.
      CONCLUSIONS: Although coverage rates for some vaccines were high, complete
      vaccination coverage remains low among children aged 13 to 59 months in Buenos
      Aires. Increasing coverage will require better access to vaccination,
      particularly in sections of the community with risk factors.

PMID- 15507184
TI  - [Syphilis positivity in puerperal women: still a challenge in Brazil].
AB  - OBJECTIVE: To investigate the factors associated with positive syphilis serology
      results in puerperal women who were receiving care at 24 health centers
      accredited by Brazil's National Program on Sexually Transmitted Diseases and
      AIDS. METHODS: This cross-sectional study included a probabilistic random sample
      of 3047 puerperal women. The eligibility criterion was being admitted for
      delivery or curettage in the selected centers. After an interview to collect
      demographic and clinical information, a blood sample was taken and then examined
      with the Venereal Disease Research Laboratory (VDRL) slide test. With positive
      VDRL results, the fluorescent treponemal antibody-absorption test (FTA-Abs) was
      used for confirmation. The event considered for analysis was positivity on the
      VDRL test, with confirmation by the FTA-Abs. For the statistical analysis, odds
      ratios and 95% confidence intervals were calculated. The model fit was assessed
      using the Hosmer-Lemeshow test. RESULTS: The prevalence of syphilis among the
      women studied was 1.7%. Multivariate analysis showed that increased risk for
      positive VDRL and FTA-Abs results was associated with the following
      characteristics: family income below one minimum wage, age < 17 years at first
      sexual intercourse, age < or = 14 years at first pregnancy, history of syphilis
      or of other sexually transmitted diseases prior to the current pregnancy,
      treatment for syphilis during the current pregnancy, partner having been tested
      for syphilis, having a positive HIV test result or having no HIV test result on
      record, previous preterm delivery, and stillbirth as an outcome of pregnancy.
      Only 43% of the women had had six or more prenatal visits, and only 3% had had
      one VDRL test during the first trimester of pregnancy and another VDRL test
      during the third trimester, as is recommended by Brazil's national Ministry of
      Health. CONCLUSIONS: This study shows that the problem of congenital syphilis is
      far from being solved in Brazil. It is necessary to provide adolescents with
      family planning services as well as guidance on sexual issues, to improve
      prenatal follow-up, and to research the history of sexually transmitted diseases
      in both the pregnant woman and her sexual partner.

PMID- 15507185
TI  - The roles of cats and dogs in the transmission of Toxoplasma infection in Kuna
      and Embera children in eastern Panama.
AB  - OBJECTIVE: To examine the relationship between antibody status and various
      hypothesized risk factors for Toxoplasma gondii infection among two different
      Amerindian populations in eastern Panama. Following up on earlier research that
      we conducted, we now explore the role of dogs in the natural transmission of
      Toxoplasma, the role that dogs play in promoting transmission, the interactive
      effect of cats and dogs, and the accessibility of infective material to children.
      METHODS: In 1991, 10 Panamanian medical students conducted interviews and took
      blood samples from 760 Kuna and Embera children aged 2 through 12 years in the
      Upper Bayano River Basin and the San Blas Islands. Serologic assays were
      performed using direct agglutination. The data analyses in the 1990s included
      univariate, bivariate, and multivariate analyses, without regard to data on dogs.
      Further bivariate and multivariate analyses were performed in 2003 to examine the
      contribution of dogs. RESULTS: In communities with high Toxoplasma antibody
      prevalence in children, logistic regression suggested that the factors predictive
      of antibody presence were: compacted soil floors of huts (P = 0.001), having a
      dog (P = 0.038), and the interviewer seeing a cat in the house (P = 0.049). Our
      results suggest that the villagers' dogs play a significant role in facilitating
      the transmission of Toxoplasma gondii to humans, most often in the presence of
      cats in the houses, and only in those communities with higher Toxoplasma
      seroprevalence in children. CONCLUSIONS: Dogs may act as mechanical vectors, by
      rolling in foul-smelling substances and by ingesting fecal material. In areas of
      high Toxoplasma prevalence in children and where dogs and cats are plentiful,
      immunocompromised individuals and pregnant women should be warned of the
      possibility of acquiring Toxoplasma gondii from dogs as well as from soil
      contaminated by cats. People should be encouraged to wash their hands after
      contact with soil, dogs, or cats as well as before eating.

PMID- 15507186
TI  - [Efficacy of biocides against hospital isolates of Staphylococcus sensitive and
      resistant to methicillin, in the province of Buenos Aires, Argentina].
AB  - OBJECTIVE: To assess the response to the action of different antiseptics and
      disinfectants usually used in Argentinian hospitals of hospital staphylococci
      sensitive and resistant to methicillin. To test the effectiveness of the biocides
      by measuring their effective bactericidal concentrations, and to determine
      whether there is any correlation between biocide resistance and methicillin
      resistance in this bacterial population. METHODS: The action of seven biocides
      was tested against 25 strains of nosocomial Staphylococcus spp. sensitive and
      resistant to methicillin, and in Staphylococcus aureus ATCC 6538. Hospital
      strains were obtained from April, 2000 to May, 2002, from clinical samples (blood
      culture, urine culture, catheter tip or abscess) from male and female inpatients
      and outpatients at two tertiary hospitals. After isolation, antibiotic
      sensitivity was tested with the agar diffusion method of Kirby and Bauer. The
      action of hospital biocides on the strains was studied with the Kelsey-Sykes
      test, which establishes the effective bactericide concentrations of these
      compounds. RESULTS: The results showed that the response of strains sensitive and
      resistant to methicillin varied in comparison to the collection strain.
      Chlorhexidine digluconate, povidone iodine, weak tincture of iodine and alkaline
      glutaraldehyde were effective against most strains, regardless of whether they
      were sensitive or resistant to methicillin. CONCLUSIONS: We found no indication
      of a relationship between resistance to methicillin and resistance to biocides.
      Our study shows that further research is needed to evaluate the efficacy of
      chemical agents against microorganisms that have been exposed to antibiotic
      therapies.

PMID- 15507187
TI  - Smoking at home is strongly associated with symptoms of asthma and rhinitis in
      children of primary school age in Trinidad and Tobago.
AB  - OBJECTIVE: To compare, in the twin-island republic of Trinidad and Tobago, the
      prevalence of symptoms of asthma and rhinitis among children of primary school
      age who are exposed to household environmental tobacco smoke with the prevalence
      of these symptoms in their colleagues without this exposure. METHODS: Between
      September and December 2002, questionnaires based on the instrument developed for
      the International Study of Asthma and Allergies in Childhood (ISAAC) were
      distributed, via the children in their schools, to parents of 6,611 Year 2 pupils
      (typically 6 years old) or Year 3 pupils (typically 7 years old) in 106 randomly
      selected schools in Trinidad and Tobago (5,511 pupils on Trinidad and 1,100
      pupils on Tobago). We added to the standard ISAAC questionnaires two questions,
      one on household smoking and one on the ethnicity of the children. RESULTS: A
      total of 3 170 completed questionnaires were suitable for further analysis (2,618
      from Trinidad and 552 from Tobago). On Trinidad 782 of the children (29.9%) lived
      in homes where one or both parents smoked, and 513 (19.6%) had other relatives in
      the household who smoked. On Tobago 94 of the pupils (17.0%) had parents who
      smoked, and 84 (15.4%) came from homes where other residents smoked. Parental
      smoking was significantly associated with wheezing (odds ratio (OR): 1.43; 95%
      confidence interval (CI): 1.11-1.83), exercise-induced wheezing (OR: 2.12; 95%
      CI: 1.59-2.82), nocturnal coughing (OR: 1.64; 95% CI: 1.37-1.97), and symptoms of
      rhinitis (OR: 1.35; 95% CI: 1.10-1.65) in the last 12 months as well as a history
      of hay fever/sinus problems (OR: 1.39; 95% CI: 1.11-1.74). Smoking in the home by
      adult residents other than parents was also significantly associated with all of
      these symptoms as well as a history of asthma (OR: 1.49; 95% CI: 1.13-1.97). In
      terms of ethnic differences, parental smoking was most prevalent in the homes of
      South Asian students, while smoking by other adults in the home occurred most
      commonly in the households of pupils of mixed race. CONCLUSIONS: Even in Trinidad
      and Tobago, which is a tropical environment where more time is spent outdoors and
      homes have more open ventilation than in temperate climates, environmental
      tobacco smoke exposure is closely associated with an increased prevalence of
      symptoms of asthma and rhinitis in primary-school-aged children.

PMID- 15507188
TI  - [Milk from human milk banks for low birthweight newborns: nutritional contents
      and supplementation].
AB  - OBJECTIVE: To determine the macronutrient and micronutrient contents of human
      milk from milk banks as well as to develop a supplement for addition to this milk
      that could satisfy the specific nutritional requirements of low birthweight
      newborns. METHOD: For the determination of macronutrients, 46 samples of
      pasteurized milk obtained from two milk banks were analyzed in triplicate: 26
      samples of mature milk, 10 samples of foremilk and 10 samples of milk from
      mothers of preterm babies. Thirty of these samples (10 of each type of milk) were
      also analyzed for their micronutrient content. Following the determination of
      macronutrients and micronutrients, an easy-to-prepare supplement was developed.
      The supplement was made from protein hydrolysate powder and chelate minerals.
      RESULTS: The nutritional content varied both among the different types of milk
      and among the donors of the same type of milk. The levels of macronutrients and
      micronutrients were below the requirements for low birthweight newborns. The mean
      composition (and standard deviation) observed for mature milk, foremilk, and
      preterm milk, respectively, was as follows: fats (g/100 mL), 2.56 (+/- 0.8), 2.48
      (+/- 0.91), 2.48 (+/- 0.76); lactose (g/100 mL), 8.6 (+/- 0.93), 7.05 (+/- 0.92),
      6.56 (+/- 1.41); protein (g/ 100 mL), 1.07 (+/- 0.22), 1.71 (+/- 0.29), 1.72 (+/-
      0.4); calories (kcal/100 mL), 61.67 (+/- 8.92), 57.36 (+/- 8.37), 55.44 (+/-
      8.00); calcium (mg/100 mL), 17.88 (+/- 5.56), 22.75 (+/- 10.24), 22.03 (+/-
      9.39); magnesium (mg/100 mL), 2.15 (+/- 0.39), 2.64 (+/- 0.67), 2.16 (+/- 0.26);
      potassium (mg/100 mL), 35.53 (+/- 7.54), 43.75 (+/- 14.32), 44.37 (+/- 12.83);
      sodium (mg/100 mL), 16.27 (+/- 5.92), 43.36 (+/- 11.34), 37.98 (+/- 11.34); zinc
      (mg/100 mL), 0.46 (+/- 0.26), 0.75 (+/- 0.25), 0.72 (+/- 0.26); and phosphorus
      (mg/100 mL), 9.98 (+/- 1.72), 9.31 (+/- 4.30), 8.47 (+/- 2.43). After the
      addition of the supplement, the protein and mineral contents reached the levels
      recommended for low birthweight newborns. CONCLUSION: Based on our results
      obtained, the supplementation of human milk from milk banks is warranted for use
      with low birthweight newborns. The proposed supplement was shown to be practical
      and safe, and it did not interfere with the microbiological quality of human
      milk.

PMID- 15507190
TI  - [Maternal syphilis and congenital syphilis in Latin America: big problem, simple
      solution].
AB  - From the data submitted to the Pan American Health Organization (PAHO) by
      nationwide programs against sexually transmitted diseases (STD), HIV infection,
      and AIDS (2002), one can estimate the overall prevalence of syphilis among
      pregnant women to be 3.1% and to range from 1.00% in Peru to 6.21% in Paraguay.
      According to these data, the incidence of congenital syphilis ranges from 1.4 per
      1000 live births in El Salvador to 12.0 per 1000 live births in Honduras. Among
      men who engage in sex with other men, who often classify themselves as
      heterosexual, as well as in female sex workers, the prevalence of syphilis ranged
      from 5% to 15%. Factors that determine the persistence of congenital syphilis as
      public health problem include a lack of awareness of the seriousness of the
      problem among politicians, health officials, and health care providers, difficult
      access to prenatal care, and screening services, a low demand for the test among
      users, and the stigma and discrimination that surround sexually transmitted
      diseases (STD). This paper seeks to focus the attention of health professionals
      on maternal and congenital syphilis so they will undertake actions, using an
      interprogrammatic approach, to eliminate congenital syphilis from Latin America
      and the Caribbean. Eliminating congenital syphilis will only become possible if
      interventions targeting vulnerable groups are also implemented. PAHO's role in
      eliminating congenital syphilis includes determining the baseline situation in
      the Region as a whole and in each country, developing communication and
      procurement strategies, supporting nationwide programs, promoting operational
      research, and facilitating interprogrammatic coordination.

PMID- 15507191
TI  - [WHO guidelines for governments and consumers regarding the use of alternative
      therapies].
AB  - Herbal remedies and other alternative treatments, such as acupuncture and
      homeopathy, are widely used in traditional societies and are becoming immensely
      popular in developed countries as well. Most are cheap, readily available, easy
      to use, and are perceived to be "healthier" than pharmaceutical substances.
      However, users need to be better informed as to the actual benefits and
      properties of these forms of therapy and their potential hazards. Improper use
      puts consumers at risk for potentially serious side effects as a result of
      allergy, drug interactions, contamination of the products with pesticides, heavy
      metals, and other substances, or trauma inflicted by inexperienced or poorly
      trained practitioners. Some traditional remedies can cause undesirable effects,
      such as excessive bleeding. Thus, it is essential that users have access to the
      information that is reliable, clear, and easily available. In June of this year
      the World Health Organization released a new set of guidelines to help national
      health authorities develop and distribute this type of information. The
      Guidelines on Developing Consumer Information on Proper Use of Traditional,
      Complementary and Alternative Medicine, which were developed with the financial
      and technical support of the Government of Lombardy, Italy, and the Government of
      Sweden, are part of a collaborative project that seeks to promote the proper use
      of traditional, complementary, and alternative therapies by consumers. In
      addition to offering advice for government officials on how to prepare reliable
      consumer information, the guidelines contain a series of simple questions that
      can guide users through the process of deciding on the use of such therapies. The
      guidelines are published in English at the World Health Organization's website:
      http://www.who.int/en/

PMID- 15507195
TI  - Beware of the AGC: the message about atypical glandular cells.

PMID- 15507196
TI  - The relationship between atypical glandular cells of undetermined significance on
      Pap smear and a clinically significant histologic diagnosis.
AB  - OBJECTIVE: To determine whether the cytologic diagnosis of atypical glandular
      cells of undetermined significance (AGUS) on Pap smear was associated with a
      clinically significant histologic diagnosis. METHODS: A retrospective cohort
      study was performed on the charts of women diagnosed with AGUS on Pap smear in 2
      referral colposcopy clinics, between January 1999 and July 2002. The factors
      considered included age, menstrual status, use of birth control pills or hormone
      replacement therapy, parity, referral Pap, type of evaluation at colposcopy,
      histologic diagnosis, and final diagnosis at pathology. RESULTS: Of the 124 women
      with a referral diagnosis of AGUS, 41 (33.1%) had significant histology at
      colposcopy. Premenopausal and nulliparous women were more likely to have a
      significant histologic diagnosis. The categories of "favour neoplastic" and
      "favour reactive" were not predictive of significant histology. Menopausal status
      was not predictive of either endometrial or endocervical disease among serious
      lesions. CONCLUSIONS: Because almost one-third of women with the finding of AGUS
      on Pap smear will have a diagnosis at the time of colposcopy that requires
      treatment, a colposcopy and endocervical curettage should be recommended to all
      women with AGUS. The new designation of "atypical glandular cells" (AGC) under
      the 2001 Bethesda classification system is appropriate, as "favour reactive" and
      "favour neoplastic" are not predictive of serious histologic findings.

PMID- 15507198
TI  - Anxieties and attitudes towards abortion in women presenting for medical and
      surgical abortions.
AB  - OBJECTIVE: To examine the differences in anxiety levels and attitudes towards
      abortion between women having an early medical abortion and women having a
      surgical (manual vacuum aspiration) abortion. METHODS: Women who presented for an
      early medical abortion or a surgical abortion at an urban, free-standing abortion
      clinic were invited to participate in this study. Fifty-nine women having a
      medical abortion and 43 women having a surgical abortion answered questionnaires
      before their scheduled abortion, and again 2 to 4 weeks after the abortion.
      Thirty women were interviewed about their answers. RESULTS: Anxiety levels were
      similar in both groups before the abortion procedure. Anti-choice views about
      abortion were seen in 60.5% of women having a medical abortion and in 37.3% of
      women having a surgical abortion (P = .027). Women who were pro-choice had a mean
      anxiety score of 5.0 (range, 0-10) before and 2.7 after the abortion, whereas
      women who were anti-choice had a mean anxiety score of 5.2 before and 4.4 after
      the abortion (P = .005). CONCLUSION: It is important for providers of abortion
      care to understand that women undergoing a medical abortion may be more
      ambivalent about abortion than women undergoing a surgical abortion, and women
      who are anti-choice but having an abortion may have unresolved anxiety after the
      procedure.

PMID- 15507197
TI  - The prediction of adverse maternal outcomes in preeclampsia.
AB  - OBJECTIVES: (1) To evaluate whether clinical variables reflecting the multiorgan
      dysfunctions of preeclampsia can predict adverse maternal outcomes of
      preeclampsia; (2) to determine the usefulness of the mean platelet volume
      (MPV):platelet ratio as a novel measure of platelet consumption in predicting the
      severity of preeclampsia. METHOD: A retrospective chart review was conducted of
      cases of preeclampsia seen in 3 tertiary level units from January 2001 to
      December 2001. Candidate predictors of adverse maternal outcome were gestational
      age (GA) on admission to hospital, blood pressure, proteinuria, urine output,
      uric acid, creatinine, aspartate transaminase (AST), lactate dehydrogenase,
      bilirubin, albumin, fraction of inspired oxygen:oxygen saturation (FIO2:SaO2)
      ratio, platelet count, MPV, MPV:platelet ratio, fibrinogen, and seizures. The
      combined adverse maternal outcomes included maternal death; 1 or more of hepatic
      failure, hematoma, or rupture; Glasgow coma scale <13; stroke; 2 or more
      seizures; cortical blindness; positive inotrope support; myocardial infarction;
      infusion of any third antihypertensive; dialysis; renal transplantation; > or
      =50% FIO2 for >1 hour; intubation; or transfusion of > or =10 units of blood
      products. Descriptive, univariable, and multivariable analyses were performed,
      with significance set at P < .05. RESULTS: Of a total of 594 women with
      preeclampsia, 60 (10.1%) developed at least 1 element of the combined adverse
      outcome; 1 of these 60 women died. The most common outcomes were increased oxygen
      requirements, the use of a third infused antihypertensive, and transfusion >10
      units. In women who developed an adverse outcome, GA and fibrinogen were lower,
      and total leukocyte count, creatinine, and AST were greater. Multivariable
      logistic regression revealed that admission GA (odds ratio [OR], 0.91), dipstick
      protein (OR, 1.31), and MPV:platelet ratio (OR, 391.0) independently predicted
      the outcome. CONCLUSIONS: Several promising markers were identified: admission
      GA, dipstick proteinuria, and the MPV:platelet ratio. MPV:platelet ratio also
      showed promise as a marker of platelet consumption. A prospective study is
      required to develop a clinical prediction model for preeclampsia.

PMID- 15507199
TI  - Risk of fetal exposure to tricyclic antidepressants.
AB  - OBJECTIVES: (1) To review the literature on the risk of fetal exposure to
      tricyclic antidepressants (TCAs). (2) To estimate the frequency of TCA exposure
      in pregnant women in the Canadian province of Saskatchewan. METHODS: MEDLINE was
      searched for English-language papers published from 1953 to 2003, using the key
      words "tricyclic antidepressants (TCAs)," "amitriptyline," "amoxapine,"
      "clomipramine," "desipramine," "doxepin," "imipramine," "lofepramine,"
      "maprotiline," "nortriptyline," "protriptyline," and "trimipramine." The search
      was restricted to human studies. To estimate potential exposure to TCAs during
      pregnancy, data from the outpatient prescription drug database of Saskatchewan,
      Canada, were analyzed. RESULTS: The number of women of reproductive age (16 to 44
      years) with at least 1 prescription of genotoxic TCAs was 3501 in 1977, 2959 in
      1991, and 1330 in 1999. Corresponding figures for non-genotoxic TCAs were 3403,
      4200, and 5493, respectively. Based on these figures, the rates of prescriptions
      given to women of reproductive age in any particular calendar year were 1.30%
      (95% confidence interval [CI], 1.25%-1.35%) for genotoxic TCAs, and 2.32% (95%
      CI, 2.25%-2.39%) for non-genotoxic TCAs. CONCLUSIONS: Prescription of TCAs to
      women of reproductive age is quite frequent, and there has been no apparent
      decline in prescriptions in recent years. The frequent prescription of
      potentially toxic TCAs to pregnant women may be due to increases in unplanned
      pregnancies in industrial countries, lack of adequate scientific evidence on the
      adverse effects of TCAs, and conflicting needs to treat maternal diseases and to
      protect fetuses. Consultation with specialists experienced in treating depression
      may be helpful when treating pregnant women with TCAs. Large-scale epidemiologic
      studies to assess the potential adverse effects of TCAs use in pregnancy on a
      broad spectrum of fetal and infant outcomes are needed. The findings from such
      studies will have direct implication on the use of TCAs in the clinical treatment
      of depression in pregnancy.

PMID- 15507200
TI  - Treatment options in fetomaternal hemorrhage: four case studies.
AB  - BACKGROUND: Significant fetomaternal hemorrhage (FMH) is an uncommon event that
      places the fetus at risk of severe morbidity and mortality. Symptoms and signs at
      presentation are subtle and, if promptly recognized, appropriate management may
      permit the fetus to escape serious injury. CASES: Four cases of significant FMH
      were diagnosed in the high-risk obstetrical unit at Mount Sinai Hospital,
      Toronto, during 2003. Three of the women complained of reduced fetal movements
      and were investigated initially with a non-stress test, a Kleihauer-Betke test,
      and ultrasound, including Doppler of the middle cerebral artery. These women all
      required emergency Caesarean section for non-reassuring fetal status. One fetus
      was treated by intravascular transfusion. Another identified case was transfused
      postnatally. One asymptomatic case was identified after spontaneous vaginal birth
      and also treated by neonatal transfusion. Neurological outcomes were good in all
      four cases. CONCLUSIONS: Reduced fetal movements may be the only complaint of
      FMH. Increased awareness is required to ensure a diagnosis is made. When a non
      stress test for reduced fetal movement is non-reactive, a Kleihauer-Betke test
      should be ordered, as well as detailed ultrasonography, including fetal Doppler
      studies. The perinatal prognosis for FMH may improve by facilitating the
      appropriate use of fetal blood transfusion or delivery by Caesarean section.

PMID- 15507201
TI  - Uterine fibroid embolization (UFE).
AB  - OBJECTIVE: To help direct the organized and effective implementation of uterine
      fibroid embolization into clinical practice in Canada. OPTIONS: This document is
      restricted to the management of uterine fibroid embolization as performed by the
      radiologists utilizing a trans-femoral artery approach with arteriography
      followed by vessel embolization. OUTCOMES: Uterine fibroid embolization has been
      evaluated in terms of patient satisfaction, risks of complications, risks in
      subsequent pregnancy and rate of hysterectomy within a few months of the
      procedure. As the procedure is relatively new, data on long-term outcomes are not
      available. EVIDENCE: Published opinions of experts, supplemented by evidence from
      clinical trials where appropriate. VALUES: The quality of the evidence is rated
      using the criteria described by the Canadian Task Force on the Periodic Health
      Examination. BENEFITS, HARMS, AND COSTS: For women presenting with symptomatic
      uterine fibroids who are candidates for UFE, there is often a benefit to avoiding
      an abdominal surgery. The risks of the UFE procedure, possible complications, and
      short- and long-term prognosis must be measured on an individual basis against
      the well-studied surgical alternatives. Patient preference is an important
      component of this evaluation. The non-material costs of ongoing symptoms from the
      fibroids are difficult to measure and use comparatively against the cost of
      hospitalization and treatment. In evaluating costs of UFE, the calculations
      should take into consideration the cost of managing occasional complications
      including subsequent hysterectomy. The cost of myomectomy or hysterectomy will
      vary largely depending on technique used and length of hospital stay.
      RECOMMENDATIONS: 1. Women considering treatment of fibroids should be counselled
      that while the early results of uterine artery embolization are encouraging, no
      long-term data exist. (II-2-B) 2. UFE should only be considered for women with
      symptomatic or problematic fibroids who might otherwise be advised to have
      surgical treatment. (III-A) 3. UFE as a treatment for fibroids in patients
      wishing to preserve their fertility should be undertaken with full disclosure to
      the patient about the limitations of such a procedure and the lack of existing
      data regarding future fertility and pregnancy outcomes. (III-C) 4. UFE is
      contraindicated in women who have evidence of current genitourinary infection
      and/or malignancy. (II-2-B) 5. Women who choose UFE as an alternative to
      hysterectomy should be counselled regarding the risk of major complications f UFE
      where hysterectomy may be urgently required and potentially lifesaving. In view
      of this small but important risk, UFE is relatively contraindicated in women who
      are unwilling to have a hysterectomy under any circumstances. (III-C) 6.
      Genitourinary infection is the predominant cause of serious morbidity and
      mortality. Further research on the utility of prophylactic antibiotic therapy and
      the value of pretreatment screening for infection is needed. (II-2-B) 7. A
      gynaecologist who is familiar with UFE should evaluate all patients considered
      for UFE before the procedure is booked and a consensus on the suitability of the
      procedure achieved between the gynaecologist and radiologist. (III-C) 8. Only
      radiologists with specialized embolization experience and techniques should
      perform UFE. (III-C) 9. The particular responsibilities of both gynaecologist and
      radiologist should be established prior to treatment and be set out in a relevant
      hospital protocol. A particular physician must be responsible for the patient at
      all times. (III-C) 10. A Canadian national registry of numbers, indications,
      outcomes, complications, and successful pregnancies associated with UFE should be
      created and jointly administered and funded by the SOGC, CAR, and CIRA. (III-C).

PMID- 15507202
TI  - Flypaper for parasites.
AB  - In this issue, Kamhawi et al. (2004) describe the identification of an insect
      galectin as the receptor for the stage-specific Leishmania adhesin
      lipophosphoglycan (LPG). This interaction is critical for parasite survival in
      the midgut of its sand fly vector. The results open new avenues for studies of
      insect immunity, transmission binding vaccines, and host-parasite coevolution.

PMID- 15507203
TI  - Factor XIIIA (cross)links AT1 receptors to atherosclerosis.
AB  - Angiotensin II, a small peptide hormone that plays key roles in the regulation of
      blood pressure, also contributes to inflammatory processes that promote the
      development of atherosclerosis. In this issue of Cell, AbdAlla et al. (2004)
      provide evidence that pathogenic actions of angiotensin II involve covalent
      crosslinking of angiotensin AT1 receptors by factor XIIIA transglutaminase,
      resulting in stable receptor dimers with enhanced signaling properties.

PMID- 15507204
TI  - Chronic myeloid leukemia: proving ground for cancer stem cells.
AB  - A central question in cancer biology is whether malignancy arises in self
      renewing tissue stem cells that suffer oncogene activation or in differentiated
      cells that acquire properties of unremitting self-renewal? In two papers,
      Weissman and colleagues document both mechanisms: chronic leukemia arising by
      mutation affecting the hematopoietic stem cell (HSC) and acute leukemia evolving
      from committed granulocyte-macrophage progenitors that have acquired the self
      renewal machinery of HSCs.

PMID- 15507205
TI  - Kinetochore orientation in mitosis and meiosis.
AB  - Kinetochores are the major point of contact between spindle microtubules and
      chromosomes. They are assemblies of more than 50 different proteins and take part
      in regulating and controlling their own interaction with the spindle. We review
      recent advance in understanding how kinetochores are properly placed onto the
      chromosome, and how their interaction with the microtubules of the spindle is
      regulated. Kinetochore orientation in meiosis I shows some particular features,
      and we also discuss similarities and differences between mitosis and meiosis I.

PMID- 15507206
TI  - Factor XIIIA transglutaminase crosslinks AT1 receptor dimers of monocytes at the
      onset of atherosclerosis.
AB  - Many G protein-coupled receptors form dimers in cells. However, underlying
      mechanisms are barely understood. We report here that intracellular factor XIIIA
      transglutaminase crosslinks agonist-induced AT1 receptor homodimers via
      glutamine315 in the carboxyl-terminal tail of the AT1 receptor. The crosslinked
      dimers displayed enhanced signaling and desensitization in vitro and in vivo.
      Inhibition of angiotensin II release or of factor XIIIA activity prevented
      formation of crosslinked AT1 receptor dimers. In agreement with this finding,
      factor XIIIA-deficient individuals lacked crosslinked AT1 dimers. Elevated levels
      of crosslinked AT1 dimers were present on monocytes of patients with the common
      atherogenic risk factor hypertension and correlated with an enhanced angiotensin
      II-dependent monocyte adhesion to endothelial cells. Elevated levels of
      crosslinked AT1 receptor dimers on monocytes could sustain the process of
      atherogenesis, because inhibition of angiotensin II generation or of
      intracellular factor XIIIA activity suppressed the appearance of crosslinked AT1
      receptors and symptoms of atherosclerosis in ApoE-deficient mice.

PMID- 15507207
TI  - Homologous recombination generates T-loop-sized deletions at human telomeres.
AB  - The t-loop structure of mammalian telomeres is thought to repress nonhomologous
      end joining (NHEJ) at natural chromosome ends. Telomere NHEJ occurs upon loss of
      TRF2, a telomeric protein implicated in t-loop formation. Here we describe a
      mutant allele of TRF2, TRF2DeltaB, that suppressed NHEJ but induced catastrophic
      deletions of telomeric DNA. The deletion events were stochastic and occurred
      rapidly, generating dramatically shortened telomeres that were accompanied by a
      DNA damage response and induction of senescence. TRF2DeltaB-induced deletions
      depended on XRCC3, a protein implicated in Holliday junction resolution, and
      created t-loop-sized telomeric circles. These telomeric circles were also
      detected in unperturbed cells and suggested that t-loop deletion by homologous
      recombination (HR) might contribute to telomere attrition. Human ALT cells had
      abundant telomeric circles, pointing to frequent t-loop HR events that could
      promote rolling circle replication of telomeres in the absence of telomerase.
      These findings show that t-loop deletion by HR influences the integrity and
      dynamics of mammalian telomeres.

PMID- 15507208
TI  - The pathway of HCV IRES-mediated translation initiation.
AB  - The HCV internal ribosome entry site (IRES) directly regulates the assembly of
      translation initiation complexes on viral mRNA by a sequential pathway that is
      distinct from canonical eukaryotic initiation. The HCV IRES can form a binary
      complex with an eIF-free 40S ribosomal subunit. Next, a 48S-like complex
      assembles at the AUG initiation codon upon association of eIF3 and ternary
      complex. 80S complex formation is rate limiting and follows the GTP-dependent
      association of the 60S subunit. Efficient assembly of the 48S-like and 80S
      complexes on the IRES mRNA is dependent upon maintenance of the highly conserved
      HCV IRES structure. This revised model of HCV IRES translation initiation
      provides a context to understand the function of different HCV IRES domains
      during translation initiation.

PMID- 15507209
TI  - Requirement of DDX3 DEAD box RNA helicase for HIV-1 Rev-RRE export function.
AB  - A single transcript in its unspliced and spliced forms directs the synthesis of
      all HIV-1 proteins. Although nuclear export of intron-containing cellular
      transcripts is restricted in mammalian cells, HIV-1 has evolved the viral Rev
      protein to overcome this restriction for viral transcripts. Previously, CRM1 was
      identified as a cellular cofactor for Rev-dependent export of intron-containing
      HIV-1 RNA. Here, we present evidence that Rev/CRM1 activity utilizes the ATP
      dependent DEAD box RNA helicase, DDX3. We show that DDX3 is a nucleo-cytoplasmic
      shuttling protein, which binds CRM1 and localizes to nuclear membrane pores.
      Knockdown of DDX3 using either antisense vector or dominant-negative mutants
      suppressed Rev-RRE-function in the export of incompletely spliced HIV-1 RNAs.
      Plausibly, DDX3 is the human RNA helicase which functions in the CRM1 RNA export
      pathway analogously to the postulated role for Dbp5p in yeast mRNA export.

PMID- 15507210
TI  - Structural analysis of autoinhibition in the Ras activator Son of sevenless.
AB  - The classical model for the activation of the nucleotide exchange factor Son of
      sevenless (SOS) involves its recruitment to the membrane, where it engages Ras.
      The recent discovery that Ras*GTP is an allosteric activator of SOS indicated
      that the regulation of SOS is more complex than originally envisaged. We now
      present crystallographic and biochemical analyses of a construct of SOS that
      contains the Dbl homology-pleckstrin homology (DH-PH) and catalytic domains and
      show that the DH-PH unit blocks the allosteric binding site for Ras and
      suppresses the activity of SOS. SOS is dependent on Ras binding to the allosteric
      site for both a lower level of activity, which is a result of Ras*GDP binding,
      and maximal activity, which requires Ras*GTP. The action of the DH-PH unit gates
      a reciprocal interaction between Ras and SOS, in which Ras converts SOS from low
      to high activity forms as Ras*GDP is converted to Ras*GTP by SOS.

PMID- 15507211
TI  - Structural mechanism for lipid activation of the Rac-specific GAP, beta2
      chimaerin.
AB  - The lipid second messenger diacylglycerol acts by binding to the C1 domains of
      target proteins, which translocate to cell membranes and are allosterically
      activated. Here we report the crystal structure at 3.2 A resolution of one such
      protein, beta2-chimaerin, a GTPase-activating protein for the small GTPase Rac,
      in its inactive conformation. The structure shows that in the inactive state, the
      N terminus of beta2-chimaerin protrudes into the active site of the RacGAP
      domain, sterically blocking Rac binding. The diacylglycerol and phospholipid
      membrane binding site on the C1 domain is buried by contacts with the four
      different regions of beta2-chimaerin: the N terminus, SH2 domain, RacGAP domain,
      and the linker between the SH2 and C1 domains. Phospholipid binding to the C1
      domain triggers the cooperative dissociation of these interactions, allowing the
      N terminus to move out of the active site and thereby activating the enzyme.

PMID- 15507212
TI  - Formin is a processive motor that requires profilin to accelerate actin assembly
      and associated ATP hydrolysis.
AB  - Motile and morphogenetic cellular processes are driven by site-directed assembly
      of actin filaments. Formins, proteins characterized by formin homology domains
      FH1 and FH2, are initiators of actin assembly. How formins simply bind to
      filament barbed ends in rapid equilibrium or find free energy to become a
      processive motor of filament assembly remains enigmatic. Here we demonstrate that
      the FH1-FH2 domain accelerates hydrolysis of ATP coupled to profilin-actin
      polymerization and uses the derived free energy for processive polymerization,
      increasing 15-fold the rate constant for profilin-actin association to barbed
      ends. Profilin is required for and takes part in the processive function. Single
      filaments grow at least 10 microm long from formin bound beads without detaching.
      Transitory formin-associated processes are generated by poisoning of the
      processive cycle by barbed-end capping proteins. We successfully reconstitute
      formin-induced motility in vitro, demonstrating that this mechanism accounts for
      the puzzlingly rapid formin-induced actin processes observed in vivo.

PMID- 15507213
TI  - JunB deficiency leads to a myeloproliferative disorder arising from hematopoietic
      stem cells.
AB  - The AP-1 transcription factor JunB is a transcriptional regulator of
      myelopoiesis. Inactivation of JunB in postnatal mice results in a
      myeloproliferative disorder (MPD) resembling early human chronic myelogenous
      leukemia (CML). Here, we show that JunB regulates the numbers of hematopoietic
      stem cells (HSC). JunB overexpression decreases the frequency of long-term HSC
      (LT-HSC), while JunB inactivation specifically expands the numbers of LT-HSC and
      granulocyte/macrophage progenitors (GMP) resulting in chronic MPD. Further, we
      demonstrate that junB inactivation must take place in LT-HSC, and not at later
      stages of myelopoiesis, to induce MPD and that only junB-deficient LT-HSC are
      capable of transplanting the MPD to recipient mice. These results demonstrate a
      stem cell-specific role for JunB in normal and leukemic hematopoiesis and provide
      experimental evidence that leukemic stem cells (LSC) can reside at the LT-HSC
      stage of development in a mouse model of MPD.

PMID- 15507214
TI  - Stimulation of serotonin transport by the cyclic GMP phosphodiesterase-5
      inhibitor sildenafil.
AB  - The serotonin (5-hydroxtryptamine, 5-HT) transporter (SERT) plays a critical role
      in the inactivation of synaptic 5-HT and has been implicated in multiple
      psychiatric and peripheral disorders. SERT regulation studies demonstrate that
      activation of cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG)-linked
      pathways can increase SERT activity. As cGMP actions are limited by cGMP-specific
      phosphodiesterase (PDEs), we investigated whether the cGMP-specific PDE5
      inhibitor sildenafil (Viagra) can stimulate 5-HT uptake and potentiate cGMP
      mediated regulation. In RBL-2H3 cells, SERT activity was stimulated by sildenafil
      in a concentration- and time-dependent manner. Sildenafil also enhanced the
      stimulation of SERT triggered by the adenosine receptor agonist 5'-N
      ethylcarboxamidoadenosine (NECA), effects blocked by the PKG inhibitor N-[2
      (methylamino)ethy]-5-isoquinoline-sulfonamide (H8). Sildenafil stimulation of 5
      HT uptake arises from an increase in 5-HT transport Vmax and is paralleled by
      elevated SERT surface antagonist binding, also H8-sensitive. These findings
      implicate cGMP-targeted PDEs in limiting the regulation of antidepressant
      sensitive 5-HT transport.

PMID- 15507215
TI  - Population pharmacokinetic-pharmacodynamic modelling of the anti-hyperalgesic
      effect of 5'deoxy-N6-cylopentyladenosine in the mononeuropathic rat.
AB  - The objective of this investigation was to characterise the pharmacokinetic
      pharmacodynamic correlation of 5'-deoxy-N6-cyclopentyl-adenosine (5'dCPA) in the
      chronic constriction injury model of neuropathic pain. Following intravenous
      administration of 5'dCPA (0.30 or 0.75 mg kg(-1)), the time course of the drug
      concentration in plasma was determined in conjunction with the effect on (1) the
      mechanical paw pressure and (2) the Von Frey Hair monofilament withdrawal
      threshold. Population pharmacokinetic-pharmacodynamic analysis was applied to
      derive individual concentration-effect relationships. For mechanical paw pressure
      a composite model consisting of an Emax model for the anti-hyperalgesic effect in
      combination with a linear model for the anti-nociceptive effect accurately
      described the data. The EC50 for the anti-hyperalgesic effect was 178+/-51 ng ml(
      1) and the slope of the anti-nociceptive effect 0.055+/-0.008 g ml ng(-1). For
      the Von Frey Hair monofilament withdrawal threshold responders and non-responders
      were observed. Typically, in responders, full pain relief was observed at
      concentrations exceeding 100 ng ml(-1). The high plasma concentrations required
      for the anti-hyperalgesic effect relative to the receptor affinity are consistent
      with restricted transport of 5'dCPA to the site of action in the spinal cord
      and/or the brain.

PMID- 15507216
TI  - Adenosine receptors involved in modulation of noradrenaline release in isolated
      rat tail artery.
AB  - Adenosine receptors involved in the modulation of noradrenaline release from
      postganglionic sympathetic nerves in rat tail artery were characterized by
      studying the effects of adenosine-receptor agonists and antagonists on
      electrically evoked tritium overflow (100 pulses, 5 Hz) and by
      immunohistochemistry. The adenosine A1 receptor-selective agonist N6
      cyclopentyladenosine (CPA; 1-100 nM) and the non-selective adenosine receptor
      agonist N-ethylcarboxamidoadenosine (NECA; 1-10 microM) decreased tritium
      overflow. These effects were blocked by the adenosine A1 receptor-selective
      antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 30 nM). The adenosine A(2A)
      receptor-selective agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N
      ethylcarboxamido adenosine (CGS 21680; 1-100 nM) enhanced tritium overflow, an
      effect blocked by the adenosine A(2A) receptor-selective antagonist 5-amino-7-(2
      phenylethyl)-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine (SCH
      58261; 20 nM) but not changed by the adenosine A(2B) receptor-selective
      antagonist N-(4-acetylphenyl)-2-[4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H
      purin-8-yl) phenoxy]acetamide (MRS 1706; 20 nM). In the presence of DPCPX (30
      nM), NECA enhanced tritium overflow, an effect abolished by MRS 1706 but not
      influenced by SCH 58261. Immunohistochemistry revealed immunoreactivity for all
      adenosine-receptor subtypes. Areas of co-localization were found for
      neurofilament with adenosine A1, A(2A) and A(2B) but not A3 receptors. In
      conclusion, the present study provides functional and morphological evidence for
      the occurrence of multiple adenosine receptor-mediated modulation of
      noradrenaline release in the rat tail: inhibition mediated by adenosine A1
      receptors and facilitation mediated by both adenosine A(2A) and A(2B) receptors.

PMID- 15507217
TI  - Dopamine D2 receptor activation increases vesicular dopamine uptake and
      redistributes vesicular monoamine transporter-2 protein.
AB  - Recent studies demonstrate that multiple dopamine receptor subtypes contribute to
      the regulation of vesicular monoamine transporter-2 (VMAT-2) activity. The
      present studies extend these findings by demonstrating that administration of the
      nonselective dopamine D2 receptor family agonist, quinpirole, rapidly increased
      vesicular dopamine uptake in purified rat striatal vesicles. This effect occurred
      in both postnatal day 40 and 90 rats, and was associated with redistribution of
      the vesicular monoamine transporter-2 (VMAT-2) within nerve terminals. Neither a
      full nor a partial dopamine D1 receptor family agonist (SKF81297 nor SKF38393,
      respectively) affected vesicular dopamine uptake per se, nor the effect of
      quinpirole. Neither the dopamine D3 nor the D4 receptor antagonists, NGB2904 and
      clozapine, respectively, altered the quinpirole-mediated increase in uptake.
      However, the nonselective dopamine D2 receptor family antagonist, eticlopride,
      prevented the quinpirole-induced increase. Taken together, these data demonstrate
      that dopamine D2 receptor subtype activation increases vesicular dopamine uptake.
      Implications of this phenomenon with regard to the treatment of Parkinson's
      disease will be discussed.

PMID- 15507218
TI  - Mu and delta opioid-stimulated [35S]GTP gamma S binding in brain and spinal cord
      of polyarthritic rats.
AB  - Polyarthritis induced by inoculation with complete Freund's adjuvant alters
      opioid peptides, but does not affect opioid receptor binding. This study was
      conducted to measure mu and delta opioid receptor-stimulated G-protein activity
      in brain and spinal cord of rats 19 days after injection of complete Freund's
      adjuvant or vehicle. Mu and delta opioid-stimulated [35S]GTPgammaS binding
      measured autoradiographically in caudate-putamen, medial thalamus and
      periaqueductal gray was unchanged in polyarthritic rats. Delta opioid-stimulated
      [35S]GTPgammaS binding was significantly decreased in the spinal cord of
      polyarthritic rats, whereas mu opioid-stimulated activity was unchanged. These
      data reveal that the functional activity of delta opioid receptors in the spinal
      cord is altered in polyarthritis.

PMID- 15507219
TI  - Effects of novel anxiolytic 4-butyl-alpha-agarofuran on levels of monoamine
      neurotransmitters in rats.
AB  - 4-butyl-alpha-agarofuran (AF-5) is a new compound derived from alpha-agarofuran,
      a constituent extracted from Aquillaria agallocha Roxb. Our previous research has
      shown that AF-5 has significant antianxiety activity in several animal models. In
      this study, an antianxiety effect was observed in a social interaction test after
      acute treatment with AF-5 (0.5-4.0 mg/kg, i.p.) in rats. Using high-performance
      liquid chromatography (HPLC)-electrochemical detection (ECD), we further
      investigated the effects of AF-5 on monoamine neurotransmitters both in rat brain
      tissues and in striatum dialysates. After acute administration of AF-5 (5.0
      mg/kg, i.p.), serotonin (5-hydroxytryptamine, 5-HT) tissue levels significantly
      decreased by 26.3%, 30.4%, and 17.4% of the vehicle-control levels, in the
      striatum, cortex, and midbrain, respectively. The dopamine level decreased by
      34.7% in the striatum and 19.0% in the midbrain, while in the hypothalamus, it
      increased to 156.6%. The epinephrine level decreased by 34.6% in the cortex. In
      cerebral microdialysis perfusates from rat striatum, the extracellular dopamine
      level declined stepwise after treatment with AF-5 (10.0 mg/kg, i.p.). By 200 min
      postinjection, the dopamine level reached a minimum, about 40% of the baseline
      value. At the same time, the extracellular levels of 5-hydroxyindolacetic acid, 3
      4-dihydroxyphenylacetic acid, and homovanillic acid increased significantly, the
      maximum values were 150%, 145%, and 175% above baseline, respectively. This study
      suggests that AF-5 is a potent anxiolytic agent, and that its beneficial action
      may be related to its effects on central monoamine neurotransmitters.

PMID- 15507220
TI  - A-317491, a selective P2X3/P2X2/3 receptor antagonist, reverses inflammatory
      mechanical hyperalgesia through action at peripheral receptors in rats.
AB  - The effect of A-317491 (5-([(3-Phenoxybenzyl)[(1S)-1,2,3,4-tetrahydro-1
      naphthalenyl]amino]carbonyl)-1,2,4-benzenetricarboxylic acid), a recently
      described selective P2X3 and P2X(2/3) receptor antagonist, on inflammatory
      mechanical hyperalgesia was examined. In the rat Freund's complete adjuvant model
      of inflammatory pain, s.c. administration of A-317491 dose-dependently reversed
      mechanical hyperalgesia. Maximum percent reversal (72%) was seen 3 h after
      administration at 10 mg/kg. Substantial plasma concentrations were measured for A
      317491 after s.c. dosing 3, 10 and 30 mg/kg. However, the brain-to-plasma
      concentration ratio, determined 1 h after a 10 mg/kg s.c. dose, indicated limited
      penetration of A-317491 into the central nervous system. As revealed by neural
      activity recorded from single C-fiber nociceptive afferent in a Freund's complete
      adjuvant-inflamed rat skin-nerve preparation, topical application of A-317491
      completely blocked afferent activation and mechanical sensitization induced by
      alpha,beta-methylene ATP, a P2X agonist. These results suggest that A-317491 is a
      peripherally acting P2X blocker. Its efficacy demonstrates the importance of
      peripheral P2X3/P2X(2/3) receptors in mediating ATP-associated mechanical
      hyperalgesia following inflammation, confirming previous suggestions of a
      significant role for P2X(2/3).

PMID- 15507221
TI  - Characterization of [3H]ZM 241385 binding in wild-type and adenosine A2A receptor
      knockout mice.
AB  - The binding of the adenosine A(2A) receptor antagonist [3H] 4-(2-[7-amino-2-(2
      furyl)[1,2,4]-triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol ([3H]ZM
      241385) to mouse brain and spinal cord was investigated. In brain homogenates,
      single-site binding was observed with a Bmax of 299+/-28 fmol mg(-1) protein and
      a Kd of 0.75+/-0.08 nM. In autoradiographic studies, there was a high density of
      specific binding of [3H]ZM 241385 in the striatum, with a very low density in the
      cortex and no binding elsewhere in the brain or in the spinal cord. All specific
      binding of [3H]ZM 241385 was lost in genetically modified mice lacking the
      adenosine A(2A) receptor, confirming the selectivity of this radioligand.

PMID- 15507222
TI  - The atypical antipsychotic quetiapine increases both noradrenaline and dopamine
      release in the rat prefrontal cortex.
AB  - Quetiapine is a novel atypical antipsychotic drug with multi-receptorial
      affinity. Using in vivo microdialysis, we investigated if quetiapine modulates
      extracellular noradrenaline and dopamine in brain areas generally believed to be
      involved in the pathophysiology of schizophrenia and in the action of
      antipsychotic drugs. Quetiapine (5, 10 and 20 mg/kg, i.p.) increased levels of
      noradrenaline in both the prefrontal cortex and the caudate nucleus, while it
      increased dopamine levels mainly in the prefrontal cortex. It is argued that the
      marked increase of dopaminergic transmission in the prefrontal cortex induced by
      quetiapine might be relevant to its therapeutical action.

PMID- 15507223
TI  - Effects of systemic injections of vilazodone, a selective serotonin reuptake
      inhibitor and serotonin 1A receptor agonist, on anxiety induced by predator
      stress in rats.
AB  - We examined the effect of Vilazodone, a selective serotonin reuptake inhibitor
      (SSRI) and serotonin 1A (5-HT(1A)) receptor agonist [Bartoszyk, G.D., Hegenbart,
      R., Ziegler, H., 1997. EMD 68843, a serotonin reuptake inhibitor with selective
      presynaptic 5-HT1A receptor agonistic properties. Eur. J. Pharmacol. 322, 147
      153.], on change in affect following predator stress. Vilazodone and vehicle
      injection (intraperitoneal) occurred either 10 min after predator stress
      (prophylactic testing), or 90 min prior to behavioral testing for the effects of
      predator stress (therapeutic testing). Predator stress involved unprotected
      exposure of rats to a domestic cat. Behavioral effects of stress were evaluated
      with hole board, plus-maze, and acoustic startle tests 1 week after stress.
      Predator stress increased anxiety-like behavior in the plus-maze and elevated
      response to acoustic startle. In prophylactic testing, Vilazodone affected stress
      potentiation of startle at doses above 5 mg/kg. Vilazodone increased stress
      elevation of startle at 10 mg/kg. Higher doses of Vilazodone (20 and 40 mg/kg)
      blocked stress potentiation of startle. In contrast, Vilazodone had no effect on
      stress potentiation of anxiety in the plus-maze. In therapeutic testing,
      Vilazodone increased stress elevation of startle at all doses. In contrast,
      therapeutic Vilazodone had no effect on stress potentiation of anxiety in the
      plus-maze. Taken together, the data suggest a prophylactic potential for
      Vilazodone in the treatment of changes in hypervigilance following severe stress.

PMID- 15507224
TI  - Prophylactic and therapeutic effects of acute systemic injections of EMD 281014,
      a selective serotonin 2A receptor antagonist on anxiety induced by predator
      stress in rats.
AB  - We examined the effect of the selective serotonin 2A (5-HT(2A)) receptor
      antagonist 7-[4-[2-(4-fluoro-phenyl)-ethyl]-piperazine-1-carbonyl]-1H-indole-3
      carbon itrile HCl (EMD 281014) [Bartoszyk, G.D., van Amsterdam, C., Bottcher, H.,
      Seyfried, C.A., 2003. EMD 281014, a new selective serotonin 5-HT2A receptor
      antagonist. Eur. J. Pharmacol. 473, 229-230.] on change in affect following
      predator stress. Predator stress involved a 5 min unprotected exposure of rats to
      a domestic cat. Behavioral effects of stress were evaluated with hole board, plus
      maze, light/dark box and acoustic startle tests 1 week after stress. Predator
      stress increased anxiety-like behavior in the plus maze, light/dark box, and
      elevated response to acoustic startle. EMD 281014 (0.001, 0.01, 0.1, 1 or 10
      mg/kg) and vehicle injection (ip) occurred either 10 min after predator stress
      (prophylactic testing), or 90 min prior to behavioral testing for the effects of
      predator stress (therapeutic testing 1 week after predator stress). In
      prophylactic testing, EMD 281014 prevented stress potentiation of startle in a
      dose dependent manner, though the most effective doses were midrange (0.01 and
      0.1 mg/kg). Prophylactic administration of EMD 281014 also prevented stress
      induced increase of open arm avoidance in the plus maze in a clear dose dependent
      manner (from 0.01 mg/kg onward). In therapeutic testing, EMD 281014 had no clear
      drug dependent effects on stress elevation of startle or on behavior of stressed
      rats in the elevated plus maze. Finally, EMD 281014 did not block the effects of
      stress on behavior in the light/dark box when given prophylactically or
      therapeutically. Findings implicate 5-HT(2A) receptors in initiation of some but
      not all lasting changes in anxiety-like behavior following predator stress.
      Potential clinical significance of findings are discussed.

PMID- 15507225
TI  - Characterization of the anxiolytic-like effects of fluvoxamine, milnacipran and
      risperidone in mice using the conditioned fear stress paradigm.
AB  - It has been known that rodents exhibit the immobility when tested in the same
      environment in which they had been previously exposed to aversive stimuli. This
      behavior is called conditioned fear stress-induced freezing behavior, and has
      been used as a model of anxiety. Using this animal model, the present study tried
      to characterize the anxiolytic-like effects of fluvoxamine, a selective serotonin
      reuptake inhibitor, milnacipran, a serotonin noradrenaline reuptake inhibitor and
      risperidone, an atypical antipsychotic in mice. Fluvoxamine (1.25-10 mg/kg,
      intraperitoneally (i.p.)) and milnacipran (0.5-4 mg/kg, i.p.) each dose
      dependently and significantly suppressed the conditioned fear stress-induced
      freezing behavior in mice, an indicator of anxiety, and milnacipran had a weaker
      effect than fluvoxamine. While risperidone also significantly suppressed freezing
      behavior at a low dose (0.01 mg/kg, i.p.), a high dose (0.04 mg/kg, i.p.)
      decreased spontaneous motor activity. On the contrary, sulpiride, a typical
      antipsychotic (2-8 mg/kg, i.p.), did not affect freezing behavior. In a
      combination study, the suppressive effect of a low dose of risperidone (0.01
      mg/kg, i.p.) on freezing behavior was significantly antagonized by the co
      administration of low/middle doses of fluvoxamine (1.25 and 2.5 mg/kg, i.p.),
      whereas a high dose of fluvoxamine (10 mg/kg, i.p.) was unaffected. Additionally,
      the co-administration of milnacipran (0.5-2 mg/kg, i.p.) also tended to inhibit
      the suppressive effect of risperidone (0.01 mg/kg, i.p.). These findings indicate
      that fluvoxamine, milnacipran and risperidone may each be clinically effective at
      treating anxiety disorders, but their effects may be attenuated in combination
      with other medications.

PMID- 15507227
TI  - Suppression of atopic-like dermatitis by treatment with antibody to lymphocyte
      function-associated antigen-1 in NC/Nga mouse.
AB  - The effect of a blocking-antibody specific for lymphocyte function-associated
      antigen-1 (LFA-1) was studied in an atopic-like dermatitis model, which was
      induced by the repeated application of picrylchloride in NC/Nga mice.
      Prophylactic treatment with anti-LFA-1 monoclonal antibody (mAb), not therapeutic
      treatment, significantly inhibited the skin severity score and the acanthosis
      with ulceration and infiltration of mast cells. Furthermore, the serum
      immunoglobulin E levels and cytokine production (interleukin-4 and interferon
      gamma) by splenocytes stimulated with anti-CD3 antibody were also inhibited by
      treatment with anti-LFA-1 mAb. Our results suggest that LFA-1 plays an important
      role in the induction phase of the atopic-like dermatitis model.

PMID- 15507226
TI  - Acidosis-induced protein tyrosine phosphorylation depends on Ca2+ influx via
      voltage-dependent Ca2+ channels in SHR aorta.
AB  - The contractile response to acidosis in isolated aorta from spontaneously
      hypertensive rat (SHR) depends upon tyrosine phosphorylation of
      phosphatidylinositol 3 kinase (PI3-kinase) and Ca2+ influx via voltage-dependent
      Ca2+ channels (VDCC). In this study, verapamil, a VDCC inhibitor, was shown to
      markedly inhibit acidic pH-induced contraction, whereas the residual contraction
      in the presence of verapamil was unaffected by the PI3-kinase inhibitor, 2-(4
      morpholinyl)-8-phenyl-4H-1-benzopyran-4-one hydrochloride (LY-294002).
      Interestingly, the LY-294002-insensitive component of contraction was further
      inhibited by verapamil in the presence of LY-294002. Western blotting revealed
      that acidosis stimulated tyrosine phosphorylation of p85, which was abolished
      when tissues were pretreated with tyrphostin 23, a tyrosine kinase inhibitor,
      verapamil or EGTA. In fura-2-loaded aortic strips, acidosis induced a rise in
      intracellular Ca2+ ([Ca2+]i) that was partially inhibited by LY-294002. The
      residual increase in [Ca2+]i caused by acidosis in the presence of LY-294002 was
      abolished by verapamil. These findings suggest that acidosis-induced Ca2+ influx
      through VDCC is the upstream event leading to the tyrosine phosphorylation of PI3
      kinase, which in turn contributes to the enhancement of Ca2+ entry to some extent
      in SHR aorta.

PMID- 15507228
TI  - Effects of chronic insulin on endothelial dysfunction of basilar arteries from
      established streptozotocin-diabetic rats.
AB  - Our goals were to determine both the effects of chronic insulin treatment on the
      impaired endothelium-dependent relaxation present in basilar arteries from
      established diabetic rats and the molecular basis of these effects. Acetylcholine
      induced relaxation in basilar artery rings was impaired in the streptozotocin
      induced diabetic group, and this impaired response was recovered by insulin
      treatment. The contraction induced by a nitric oxide synthase inhibitor was
      decreased in the insulin-untreated diabetic group, but was increased by insulin
      or NAD(P)H oxidase inhibitor treatment. The manganese-superoxide dismutase (Mn
      SOD) mRNA level was significantly lower in basilar arteries from insulin
      untreated diabetic rats than in those from the controls, whereas the mRNA for
      gp91phox, an NAD(P)H oxidase subunit, was increased. In the insulin-treated
      group, the basilar artery p22phox mRNA level was reduced (vs. insulin-untreated
      diabetic). These results suggest that the presence of endothelial dysfunction in
      the diabetic basilar artery is related to increased oxidative stress, and that
      insulin preserves endothelial function by alleviating oxidative stress.
      Furthermore, we directly demonstrated that the expression profile for SOD and
      NAD(P)H oxidase was altered in the streptozotocin-induced diabetic basilar
      artery.

PMID- 15507229
TI  - Effect of chronic insulin on cromakalim-induced relaxation in established
      streptozotocin-diabetic rat basilar artery.
AB  - Our goals were to determine whether the response of the rat isolated basilar
      artery to activation of ATP-sensitive potassium (KATP) channels is altered in
      diabetes mellitus, and to determine the effect of chronic insulin treatment on
      this response in established diabetic rats. The relaxation induced by cromakalim,
      an activator of KATP channels, was significantly weaker in insulin-untreated
      streptozotocin-induced diabetic rats than in the controls. This impairment was
      significantly improved following chronic administration of insulin. The
      relaxations induced by two Ca2+-activated K+-channel activators [1-ethyl-2
      benzimidazolinone (1-EBIO) or 1, 3-dihydro-1-[2-hydroxy-5
      (trifluoromethyl)phenyl]-5-(trifluoromethyl)-2H-benzimidazol-2-one (NS1619)] were
      not significantly different between control and insulin-untreated diabetic rats.
      The sodium nitroprusside-induced relaxation was similar among the three groups
      (control, diabetic, and insulin-treated diabetic). These results suggest that:
      (a) the impaired cromakalim-induced relaxation seen in diabetic rats is not due
      to a nonspecific effect of diabetes mellitus on vasorelaxation, but at least
      partly to an effect on KATP channels, and (b) that this impaired relaxation can
      be restored by chronic insulin treatment.

PMID- 15507230
TI  - Quinolizidine alkaloids isolated from Lupinus species enhance insulin secretion.
AB  - We have analyzed the effect of quinolizidine alkaloids from Lupinus species upon
      insulin secretion. Isolated normal rat islets were incubated with 3.3, 8.3, and
      16.7 mM glucose, in the presence or absence of different concentrations of
      lupanine (0.05, 0.5, and 1.0 mM), 13-alpha-OH lupanine, 17-oxo-lupanine, and 2
      thionosparteine. Insulin release was measured by radioimmunoassay. While 2
      thionosparteine enhanced insulin secretion at all glucose concentrations,
      lupanine did at 8.3 and 16.7 mM, and 13-alpha-OH lupanine or 17-oxo-lupanine only
      at 16.7 mM glucose. Diazoxide (0.1 mM) decreased the effect of all alkaloids,
      without suppressing it completely. Consequently, blockage of beta-cell K(ATP)
      sensitive channels is at least one of the mechanisms involved in the enhancing
      secretagogue effects of quinolizidine alkaloids. The fact that 13-alpha-OH
      lupanine and 17-oxo-lupanine only exert their secretagogue effect at high glucose
      concentrations could be of additional value when considering their potential use
      in the treatment of type 2 diabetes.

PMID- 15507231
TI  - Early chemokine expression induced by interferon-gamma in a murine model of
      Hashimoto's thyroiditis.
AB  - Chemokines represent a group of small, secreted proteins mainly involved in
      navigating leukocytes towards site of inflammation. Some chemokines have been
      implicated in the pathogenesis of autoimmune diseases, which are characterized by
      an ectopic retention of leukocytes within the target organ, ultimately leading to
      loss of function. To determine the chemokines profile expressed in the thyroid
      gland upon chronic exposure to interferon-gamma (IFNgamma), we analyzed C57BL6
      transgenic mice that aberrantly express IFNgamma under control of the
      thyroglobulin promoter. We compared by reverse transcriptase PCR the thyroidal
      expression of 10 chemokines (CCL1 through 5 and CXCL9 through 13) in thyr
      IFNgamma transgenics and wild-type littermates. We found that transgenics
      exclusively expressed CCL4, CXCL9, and CXCL11, and showed increased expression of
      CCL5 and CXCL10. This chemokine profile was associated with moderate mononuclear
      cell infiltration of the thyroid stroma that, however, decreased significantly
      after 2 months of age and did not organize into lymphoid structures. Our findings
      indicate that the isolated expression of IFNgamma is capable of recruiting
      mononuclear cells but they do not progress to full lymphoid transformation of the
      thyroid.

PMID- 15507232
TI  - p62 is involved in the mechanism of Mallory body formation.
AB  - p62 is a scaffolding protein that binds to polyubiquitin. It is involved in the
      degradation of proteins by the proteasome. To determine if p62 is critical in the
      development of Mallory bodies (MBs), primary culture hepatocytes from drug-primed
      mice were studied and the results were compared with normal hepatocytes. Gene
      specific gripNA (gp62) was added to the medium of the primary cultures of the
      hepatocytes to inhibit the expression of p62. Overexpression of p62 was achieved
      by transfecting the hepatocytes with a plasmid containing green fluorescent
      protein (GFP) fused p62 (p62-GFP). Gp62 dramatically inhibited MB formation by
      94% in drug-primed hepatocytes. The cells transfected with gp62 had decreased
      protein levels of p62, ubiquitin (Ub), and cytokeratin 8 (CK8). Overexpression of
      p62 accelerated and enhanced MB formation by 339% in drug-primed hepatocytes.
      Overexpression of p62 in normal mouse hepatocytes induced MB-like aggresomes that
      were stained by Ub but not by CK8. The results indicate that p62 is involved in
      the mechanism of MB formation.

PMID- 15507233
TI  - Retinoid-induced epidermal hyperplasia in human skin organ culture: inhibition
      with soy extract and soy isoflavones.
AB  - Organ cultures of human skin were incubated for 8 days with 1 microg/ml 14-all
      trans retinoic acid (14-all trans RA) and concomitantly treated with varying
      concentrations of soy extract. The epidermis of organ cultures treated with 14
      all trans RA alone underwent a hyperplastic response. In cultures treated with a
      combination of 14-all trans RA and soy extract (4-40 microg/ml), hyperplasia was
      reduced by 16-41%. The same concentrations of soy extract that reduced epidermal
      hyperplasia in organ culture also suppressed proliferation of rapidly growing
      keratinocytes in monolayer culture (approximately 25% reduction at 20 and 40
      microg/ml). On the other hand, soy extract did not further inhibit proliferation
      of quiescent keratinocytes; rather, it stimulated growth (50-52% increase
      relative to control). When dermal fibroblasts were examined for a response to soy
      extract (i.e., proliferation and synthesis of type I procollagen), both responses
      were stimulated (proliferation: 75% increase and collagen production 114%
      increase relative to control). Genistein, the major isoflavone in extracts of soy
      also inhibited epidermal hyperplasia in organ culture (34-40% reduction relative
      to control). The same concentrations that reduced epidermal hyperplasia (0.5-1.0
      microg/ml) also inhibited keratinocyte proliferation in monolayer culture but had
      little effect on fibroblast growth. Two other isoflavones (daidzein and
      glycetein) were also inhibitory, but were less effective than genistein. Taken
      together, these data suggest that use of soy extract or its constituent
      isoflavones in conjunction with 14-all trans RA may provide a way to mitigate
      unwanted epidermal effects of topical retinoid therapy without compromising
      beneficial retinoid effects in the dermis.

PMID- 15507234
TI  - Liver hypoxia and lack of recovery after reperfusion at high blood alcohol levels
      in the intragastric feeding model of alcohol liver disease.
AB  - The purpose of this study was to test for the presence of liver hypoxia and
      recovery after reperfusion when blood alcohol levels (BAL) are high. Male rats
      were fed ethanol intragastrically at a constant rate for 1 month. The pO(2)
      levels were then measured on the liver surface of these rats, in vivo during
      laparatomy under isoflurane anesthesia. To measure the response to acute hypoxia,
      the hepatic blood flow was clamped off at the porta hepatis. When the clamp was
      released, recovery from hypoxia was measured. A number of hypoxic-inducible genes
      in the liver were analyzed by means of quantitative RT-PCR as a measure of
      increased activation of hypoxia initiated transcription. The mRNA levels of genes
      for adrenomedullin, adrenergic receptor alpha, 1a and 1d, CDK inhibitor 1a, and
      erythropoietin were all significantly higher at the peaks than troughs.
      Expression of these same genes in the livers of control rats fed dextrose was
      lower than at the troughs. Although the mRNA level of the hypoxia-inducible
      factor (HIF-1alpha) was higher at the trough than at the peak, its protein
      concentration in the nuclear fraction was not increased at the troughs compared
      with the peaks. In fact, the nuclear protein level of HIF-1alpha at the peak was
      significantly higher than in control samples, which is consistent with the
      presence of hypoxia at the peaks. Further analysis of the HIF-alpha degradation
      regulation revealed that prolyl 4-hydroxylase (P4ha1) and von Hippel-Lindau
      syndrome homolog (Vhl) were both up-regulated at the troughs compared with the
      peaks. The liver surface oxygen levels at the peaks were reduced compared with
      the control samples. The pO(2) levels fell abruptly when the vessels at the porta
      hepatis were clamped. When the clamp was removed, allowing reperfusion of the
      liver, pO(2) returned to baseline levels in the control, and at the troughs but
      not at the peaks. These results support the hypothesis that hypoxia occurs at the
      peaks of the BAL cycle and recovery from ischemia is impaired at the peaks.

PMID- 15507235
TI  - APC gene loss of heterozygosity, mutations, E1317Q, and I1307K germ-line variants
      in sporadic colon cancer in Croatia.
AB  - Colorectal carcinomas are characterized by multiple genetic aberrations that
      occur during tumorigenesis. Several tumor suppressor genes associated with
      colorectal carcinoma have been identified: MCC, APC, p53, nm23-H1, DCC, DPC4. We
      examined 73 cases of sporadic human colon cancer and corresponding normal tissue
      samples to evaluate the loss of heterozygosity (LOH) at the APC gene loci. The
      purpose of this study was also to evaluate whether the LOH at the APC gene is
      associated with clinicopathological characteristics in sporadic colon cancer. We
      also investigated presence and the frequency of the most common APC gene
      mutations and APC E1317Q and I1307K germ-line variants in Croatian colorectal
      cancer patients. Five markers in all patients were found to be heterozygous and
      informative for LOH analysis. LOH at the APC locus was detected in 30.1% of
      tumors were examined. The majority of APC gene LOH was observed in Dukes' B
      (55.6%) and in the moderately differentiated tumors (42.9%). Only 1309 APC gene
      mutation was detected in our samples. In one tumor sample, a new sporadic
      mutation of the APC gene in codon 1374 was detected. APC E1317Q and I1307K germ
      line variants were not detected in our population. But APC E1317Q sporadic
      mutation was found in one tumor sample.

PMID- 15507236
TI  - Drug-induced increased mitochondrial biogenesis in a liver biopsy.
AB  - Oncocytic changes seen in hepatocytes in patients receiving highly active
      antiretroviral therapy (HAART) are a result of mitochondrial damage. This is the
      first report that provides the electron microscopy illustration of mitochondrial
      proliferation as a result of the HAART drug Stavudine (Zerit) hepatotoxicity. The
      drug's effect on mitochondrial DNA replication leads to depleted mitochondrial
      encoded proteins and configurational defects of the mitochondrial inner membrane
      leading to reduced and abnormal cristae, which house the electron transport chain
      and elementary bodies. This results in a decrease in the NAD/NADH ratio and
      reduces oxidative phosphorylation. The shift in the NAD/NADH ratio decreases the
      rate of fatty acid beta oxidation and oxidation of pyruvate by the Krebs cycle.
      Decreased oxidation of pyruvate drives it into an alternative pathway to form
      lactate leading to lactic acidosis. This mitochondrial dysfunction results in a
      compensatory increase in mitochondrial biogenesis, which results in oncocytic
      changes of the hepatocytes.

PMID- 15507237
TI  - Development of bladder urothelial hyperplasia and carcinoma in portacaval shunted
      rats is not dependent upon urolithiasis.
AB  - The pathogenesis of bladder tumors is poorly understood, possibly due to the lack
      of a suitable experimental model that is drug-free. The aim of the present study
      was to determine whether bladder tumors could be reproduced reliably in
      portacaval anastomosis (PCS) rats and whether induction is due to urolithiasis
      from the development of bladder stones. Eighteen male Sprague-Dawley rats were
      anaesthetised with isoflurane. Twelve were subjected to portacaval anastomosis
      and allowed to recover for 38 weeks and the remaining 6 underwent sham control
      procedures. They were then re-anaesthetised, the anastomosis checked for patency
      and the bladders and livers excised, fixed, block-mounted, sectioned and stained
      with haematoxylin and eosin staining for histological examination. None of the
      control rats developed bladder wall abnormalities of any recognisable nature.
      However, 5 (42%) of the PCS group had urothelial lesions and bladder stones
      present and a further 5 (42%) had urothelial lesions alone with no recognisable
      evidence of bladder stone formation. One PCS rat had bladder stones alone and the
      remaining PCS rat had an apparently normal bladder epithelium and no stones.
      Thus, 10 (83%) of the 12 PCS rats developed epithelial lesions and half of these
      did not display evidence of bladder stone formation. This represented a highly
      significant difference between the development of bladder stones and the
      occurrence of urothelial lesions in PCS rats (P > 1.0, chi(2) analysis).
      Urothelial lesions, therefore, can be reproduced in PCS rats. Their occurrence
      appears independent of bladder stone formation.

PMID- 15507238
TI  - The effect of rotenone on the urinary ethanol cycle in rats fed ethanol
      intragastrically.
AB  - Chronic ethanol ingestion alters mitochondrial function in the liver including
      inhibition of complex I of the electron transport chain. This leads to a shift in
      the NAD/NADH ratio to the reduced state when blood ethanol levels are high.
      Rotenone also inhibits complex I and induces a reduced state. The combination of
      ethanol feeding and rotenone toxicity should amplify the reduced state and block
      the cyclic increase and decrease in the rate of metabolism in the liver. The
      change in the redox state occurs during the urinary ethanol cycle in the
      intragastric tube feeding rat model of alcoholic liver disease. To test this
      hypothesis, rats were fed ethanol with rotenone and the 24-h urinary ethanol
      levels were measured daily. When ethanol was fed alone, the urinary ethanol cycle
      occurred. However, when ethanol was fed with rotenone the cycle was prevented and
      the urinary ethanol levels remained at the 200-mg% range. The rats fed ethanol or
      fed ethanol plus rotenone had the same increase in the pathology score and ALT
      elevations in the blood. Rotenone fed alone had the same normal values as the
      dextrose pair fed control rats. The results indicate that the UAL cycle is driven
      by fluctuation in the NAD/NADH ratio. When this fluctuation is blocked by
      rotenone, the cycle does not occur. It is concluded that the urinary ethanol
      cycle is dependent on cyclic fluctuation of the NAD/NADH ratio, which regulates
      the rate of ethanol elimination.

PMID- 15507239
TI  - MHC class II-related genes expression in porcine-serum-induced rat hepatic
      fibrosis.
AB  - Genes, especially MHC class II-related genes, expression was examined in porcine
      serum (PS)-induced hepatic fibrosis model. Brown-Norway (BN) and Wistar rats were
      injected intraperitoneally with 0.5 ml sterile porcine serum twice a week for 1,
      2, 3, 4, and 8 weeks. Histopathologically, inflammation started at 2 weeks in BN
      and at 4 weeks in Wistar rats, and hepatic fibrosis developed at 4 weeks in BN
      rats and at 8 weeks in Wistar rats. Microarray analysis done at 2 and 4 weeks
      revealed that the expression of MHC class II-related genes and acute phase
      inflammation-related genes significantly increased at 2 weeks in BN and at 4
      weeks in Wistar rats. On the other hand, the expression of some transcription
      related genes was down-regulated in both strains. In BN rats, the results of
      semiquantitative RT-PCR analysis done on four MHC class II-related genes mRNAs
      corresponded well with those of microarray analysis. MHC class II is considered
      to be involved in the initiation of PS-induced hepatic fibrosis in rats.

PMID- 15507240
TI  - Differential modulation of gene expression among rat tissues with warm ischemia.
AB  - The aim of this study is to determine if warm ischemia after surgical extirpation
      impacts gene expression in tissue samples which will be used for cDNA array
      analysis. We investigated effects of warm ischemia on gene expression in lung,
      liver, kidney, and spleen of rats, chronologically, using an original cDNA array,
      real-time quantitative RT-PCR and immunohistochemistry. Although no visible
      alteration was found in RNA quality, cDNA array showed that expression of many
      genes was modulated by warm ischemia within 60 min in these tissues, 19.1% of the
      tested genes in lung, 11.0% in liver, 5.1% in kidney, and 16.2% in spleen.
      Quantitative RT-PCR revealed that warm ischemia significantly induced up
      regulation of immediate early genes, c-fos, Egr-1, and c-jun, in lung, but not in
      liver. These findings suggest that genes may show tissue-dependent differential
      transcriptional response against warm ischemia. Tissue samples obtained from
      patients during surgery cannot completely escape effects of ischemia. In case of
      examination by cDNA array analysis, biologists should keep in mind that tissue
      samples come equipped with particular footprints.

PMID- 15507241
TI  - Increase in p21 expression independent of the p53 pathway in bleomycin-induced
      lung fibrosis.
AB  - Although a number of animal models have been used to study the pathogenesis of
      lung disease, to date few studies have looked at changed in the expression of
      cell cycle regulatory genes. We have studied the variation in the expression of
      p21, p53, p27 and PCNA in bleomycin-induced lung fibrosis using animal mouse
      models using immuno-histochemistry and gene-expression analysis. No difference in
      the p53, PCNA and p27 expressions were observed from the bleomycin-induced
      fibrosis when compared to saline-induced non-fibrotic lungs. Although no
      difference in nuclear p21 expression was observed, the level of cytoplasmic p21
      expression was found to be higher in fibrotic lungs at day 14 after bleomycin
      injection. p21 expression was found to increase independent of p53 in fibrotic
      lungs at 14 days after bleomycin induction.

PMID- 15507242
TI  - Immunohistochemical localizations of secretin, cholecystokinin, and somatostatin
      in the rat small intestine after acute cisplatin treatment.
AB  - Cisplatin (CDDP) is an antitumor platinum complex that causes the well-studied
      side effect of renal tubular failure. In the present study, the acute effects of
      CDDP treatment on the localization of gut hormones in the rat small intestine
      were examined by immunohistochemistry. Male Sprague-Dawley rats were used for
      these experiments. Rats were injected intravenously with CDDP (3 mg/kg) in saline
      or were left untreated (control). After the rats were euthanized at 1, 3, 5, or
      10 days after CDDP treatment, the small intestines (duodenum, jejunum, and ileum)
      were quickly removed, fixed, embedded in paraffin, and cut. No mucosal toxicity
      was detected by histopathological observation in any of the intestines of CDDP
      treated rats. The immunohistochemical detection was performed using anti
      secretin, anti-cholecystokinin (CCK), and anti-somatostatin with the avidin
      biotin-immuno-peroxidase procedure. The total number of immunoreactive cells per
      complete cross-section was counted. In the duodenum, the numbers of secretin
      immunoreactive cells and somatostatin-immunoreactive cells were dramatically
      increased 5 days after CDDP treatment. In the jejunum, the number of CCK
      immunoreactive cells was increased 1 day after CDDP treatment and those of
      secretin-immunoreactive cells and CCK-immunoreactive cells were increased 5 days
      after CDDP treatment. In the ileum, the number of CCK-immunoreactive cells was
      increased 1 day after CDDP treatment. The change in the secretin-immunoreactive
      cell count may be caused by metabolic inhibition of gastrin following CDDP
      induced nephrotoxicity. The change in the CCK-immunoreactive cell count may
      promote the excretion of bile. Therefore, somatostatin may regulate secretin and
      CCK secretion. We conclude that the distribution of these hormone-immunoreactive
      cells in the rat small intestine might be controlled by CDDP-induced
      nephrotoxicity without gut mucosal toxicity.

PMID- 15507243
TI  - Fatal fat embolism following amphotericin B lipid complex injection.
AB  - A case of amphotericin B lipid complex induced fatal fat embolism is described. A
      41-year-old Caucasian man with AIDS was undergoing treatment for cryptococcal
      meningitis with amphotericin B. His course was complicated by renal failure
      necessitating a change in therapy to amphotericin B lipid complex (Abelcet). At
      approximately 48 h, the patient developed tachycardia, tachypnea, respiratory
      failure, decline in hematocrit, thrombocytopenia, and alteration in mental
      status. Autopsy findings included fat emboli involving heart, lungs, kidney, and
      brain. To our knowledge, this is the first case report of a fatal fat embolism
      caused by intravenous liposome drug delivery.

PMID- 15507244
TI  - Psychological medicine: obstacles to delivery.

PMID- 15507245
TI  - Screening for psychiatric disorders in patients with skin diseases: a performance
      study of the 12-item General Health Questionnaire.
AB  - OBJECTIVE: Although psychiatric disorders are frequent among dermatological
      patients, no study has formally assessed the performance of any psychiatric
      screening questionnaire in dermatological practice. This study tested the ability
      of the 12-item General Health Questionnaire (GHQ-12) to identify psychiatric
      morbidity in dermatological patients. METHODS: A sample of 521 adult inpatients
      (81% of all eligible patients) completed the GHQ-12 and were administered the
      Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I) by a trained
      mental health professional masked to GHQ-12 score. RESULTS: The Receiver
      Operating Characteristic (ROC) analysis showed that GHQ-12 possesses substantial
      discriminatory ability (area under the curve=0.70). The best balance between
      sensitivity (68%) and specificity (64%) was found at the GHQ-12 cutoff score of
      3/4. This threshold gave a likelihood ratio for a positive or negative result of
      1.90 and 0.50, respectively. CONCLUSION: The performance of GHQ-12 was reasonably
      good for a self-administered questionnaire requiring only a few minutes to be
      completed and scored. Its routine use might increase recognition of psychiatric
      disorders in dermatological patients and contribute to improve patients' outcome.

PMID- 15507246
TI  - Screening for psychiatric disorders in patients with skin diseases.

PMID- 15507247
TI  - The relationship between tourists' agreeableness and openness to experience with
      coronary heart disease mortality.
AB  - OBJECTIVE: This study examined relationships between tourists' agreeableness and
      openness to experience (AOE) and rates of coronary heart disease (CHD) mortality
      in an international context. METHODS: AOE was obtained from the "Expedia Tourist
      Survey" (2002), which asked tourist office staff in 17 places around the world to
      nominate the two countries with the "best" and two with the "worst" tourists. AOE
      reflected tourists' behaviour, politeness, interest in other countries' language
      and foods, and spending money. Rates of CHD mortality were obtained for 22 of the
      countries, from published epidemiological studies. RESULTS: Controlling for
      alcohol consumption and national health budget, countries with low AOE had higher
      rates of CHD mortality than countries with high AOE. This was found in both men
      and women. CONCLUSIONS: AOE may be a risk factor of CHD mortality, a concept that
      is the antonym of hostility. If replicated with standardized AOE measures, these
      findings may have relevance to preventing CHD mortality.

PMID- 15507248
TI  - Psychological distress, physical illness and mortality risk.
AB  - BACKGROUND: Psychological distress has been associated with an increased risk of
      overall and disease-specific mortality risk. This study examines whether the
      length of follow-up time influences mortality risk. METHODS: The associations
      between psychological distress and all-cause and coronary heart disease mortality
      were modelled using proportional hazards modelling in a prospective cohort study
      of 6920 men and women aged 45-64 years. Psychological distress was assessed at
      baseline using the 30-item General Health Questionnaire (GHQ-30). RESULTS:
      Psychological distress was associated with a 5-year all-cause mortality (RR 1.68
      95% CI 1.07-2.62) and CHD mortality (RR 1.64 95% CI 1.02-2.56) in men after
      adjustment for sociodemographic and CHD risk factors, but not after further
      adjustment for baseline physical illness (RR 1.41 95% CI 0.88-2.23) for all-cause
      mortality (RR 1.39 95% CI 0.88-2.21) for CHD mortality. Psychological distress
      was not associated with all-cause and CHD mortality at 15- and 20-year follow-up.
      CONCLUSIONS: Psychological distress is a reflection of baseline physical illness
      that increases mortality risk. Psychological distress maybe on the causal pathway
      between physical illness and mortality risk.

PMID- 15507249
TI  - Can mortality studies change clinical care and health policy? Commentary on
      "Psychological distress, physical illness, and mortality risk," by Farhat Rasul,
      MSc, Stephen Stansfield, PhD, Carole Hart, PhD, Charles Gillis, MD.

PMID- 15507250
TI  - Somatoform disorders as disorders of affect regulation: a study comparing the TAS
      20 with non-self-report measures of alexithymia.
AB  - OBJECTIVE: To determine the role of undifferentiated and dysregulated affects in
      somatoform disorders by using a multimethod assessment approach of alexithymia.
      METHODS: Forty patients with ICD-10 somatoform disorders (SoD) and 20 healthy
      controls, matched for age, education and sex, were included in the study.
      Alexithymia was assessed using the Toronto Alexithymia Scale (TAS-20), the Affect
      Consciousness Interview (ACI), and the Levels of Emotional Awareness Scale
      (LEAS). All classifications were made blinded with regard to clinical status.
      RESULTS: Scores of the ACI and the TAS-20 showed that alexithymia is higher in
      SoD than in healthy controls. No differences were found on the LEAS. In terms of
      the multidimensionality of the alexithymia construct, our results indicate a
      specific positive association between SoD and a proneness to experience
      undifferentiated affects. The three subfactors of the TAS-20 were differentially
      related to non-self-report measures of alexithymia and to negative affectivity
      (NA). Only the cognitive facet of the TAS-20 (externally oriented thinking [EOT])
      was related to the LEAS and the ACI. In contrast, the affective facets of the TAS
      20-difficulties identifying feelings (DIF) and difficulties describing feelings
      (DDF)-were substantially related to NA. CONCLUSION: The findings highlight the
      important role of impaired affect regulation and NA in the process of
      somatization.

PMID- 15507251
TI  - Negative affectivity and the influence of suggestion on asthma symptoms.
AB  - OBJECTIVE: To investigate the effect of suggestion on subjective and objective
      asthma symptoms as a function of negative affectivity of the patients. METHODS:
      Asthmatics (n=32) took puffs from three separate placebo inhalers, being
      described as an inert (practice) substance, a bronchoconstrictor, and a
      bronchodilator. Negative affectivity, social desirability, probability of
      medication-intake, intensity of asthma symptoms and total respiratory resistance
      were measured at onset. The latter three measures were repeated after each trial.
      Heart rate, end tidal PCO(2), and breathing behaviour were measured during each
      trial. RESULTS: Asthmatics with high negative affectivity had overall more
      intense asthma symptoms. They also reported more airway obstruction after
      suggested bronchoconstriction and less after suggested bronchodilation, whereas
      persons with low negative affectivity did not show such variation. These effects
      were unrelated to social desirability. Respiratory symptoms correlated with the
      odds of medication intake. Neither negative affectivity nor suggestion influenced
      lung function and only breathing parameters under voluntary control changed as a
      function of suggestion. CONCLUSION: Self-reported symptoms of asthmatics with
      high negative affectivity are more influenced by suggestion than those of
      patients with low negative affectivity.

PMID- 15507252
TI  - Anger and hostility in adolescents: relationships with self-reported attachment
      style and perceived parental rearing styles.
AB  - OBJECTIVE: To examine relationships between self-reported attachment style and
      parental rearing behaviors, on the one hand, and anger/hostility, on the other
      hand, in a sample of nonclinical adolescents (N=441). METHOD: Participants
      completed (a) a single-item measure of attachment style; (b) a questionnaire
      measuring perceptions of parental rearing behaviors; and (c) two scales assessing
      anger and hostility. RESULTS: Self-reported attachment style was related to
      anger/hostility. That is, adolescents who defined themselves as avoidantly or
      ambivalently attached displayed higher levels of anger/hostility than adolescents
      who classified themselves as securely attached. Furthermore, perceived parental
      rearing was also related to anger/hostility. More specifically, low levels of
      emotional warmth and high levels of rejection, control, and inconsistency were
      accompanied by high levels of anger/hostility. Finally, regression analyses
      showed that both attachment status and parental rearing behaviors accounted for a
      unique and significant proportion of the variance in anger/hostility. CONCLUSION:
      These findings are in keeping with the notion that family environment factors
      such as attachment style and parental rearing are involved in the development of
      anger/hostility in youths.

PMID- 15507253
TI  - Validity of the Type D personality construct in Danish post-MI patients and
      healthy controls.
AB  - OBJECTIVE: Type D personality has been associated with increased risk of
      depression, vital exhaustion, social alienation, a higher number of
      reinfarctions, and higher mortality rates in patients with established coronary
      artery disease (CAD) independent of traditional biomedical risk factors. The
      construct was developed in Belgian cardiac patients, but little is known about
      its applicability in other nationalities. The objectives of the present article
      were to cross-validate the Type D Personality Scale-16 (DS16) in a Danish sample
      of patients with a first myocardial infarction and a random sample of healthy
      controls, and to investigate whether Type D is associated with posttraumatic
      stress disorder (PTSD). METHODS: A questionnaire was given to 112 consecutive
      patients with a first myocardial infarction 4 to 6 weeks post infarction, and to
      115 healthy controls selected randomly from the general population. RESULTS: The
      two-factor structure of the DS16 and the internal consistency of the Negative
      Affectivity (alpha=.83) and Social Inhibition (alpha=.76) subscales were
      confirmed. The construct validity of the DS16 was confirmed against scales that
      measure similar constructs, and the discriminant validity of the DS16 against
      measures of psychopathology. In a pooled sample of patients and healthy controls,
      comparison of both groups confirmed that Type D may be conceptualised as a marker
      of general emotional distress, with Type D persons scoring higher on depression,
      anxiety, and the PTSD symptom clusters arousal and avoidance compared with non
      Type D persons. A regression analysis run in two steps showed that the inclusion
      of Type D in the model lead to an improvement in the level of prediction of PTSD
      above and beyond a model that included gender, age, MI, neuroticism, and
      extroversion. Type D (OR=4.46; 95% CI: 1.36 to 14.64), diagnosis of MI (OR=4.03;
      95% CI: 1.43 to 11.35), and neuroticism (OR=1.32; 95% CI: 1.13 to 1.53) were
      independently associated with PTSD, adjusting for all other variables.
      CONCLUSION: These findings indicate that the Type D construct is equally
      applicable in Danish patients with CAD, and that Type D is associated with PTSD.

PMID- 15507254
TI  - Personality in men with eating disorders.
AB  - OBJECTIVE: This study compares personality variables of men with eating disorders
      to women with eating disorders. METHOD: Data were obtained from an international
      study of the genetics of eating disorders. Forty-two male participants were age
      band matched at 1:2 ratio to females from the same study. Personality features
      were compared between males and females controlling for diagnostic subgroup.
      RESULTS: Males with eating disorders appear to be slightly less at risk for
      perfectionism, harm avoidance, reward dependence, and cooperativeness than
      females. Few differences were found when diagnostic subgroup was considered.
      CONCLUSION: Observed differences in personality variables may help explain the
      difference in incidence and prevalence of eating disorders in men and women.

PMID- 15507255
TI  - Response of Taiwanese obese binge eaters to a hospital-based weight reduction
      program.
AB  - OBJECTIVE: To investigate the characteristics and prevalence of binge eating
      among overweight Taiwanese and to determine the effect of binge eating on outcome
      of weight loss treatment. METHODS: One hundred and eighty-nine participants in a
      12-week traditional weight-reduction program were classified on the basis of the
      Bulimic Investigation Test, Edinburgh (BITE) scores into binge eaters (>/=20),
      subthreshold binge eaters (10-19), and nonbinge eaters (0-9). RESULTS: This study
      found a 15.9% prevalence of binge eating. The binge-eating groups (binge eaters
      and subthreshold binge eaters) were younger, had an earlier onset of obesity, and
      more psychological distress than nonbinge eaters. Differences in obesity
      treatment weight loss among binge eaters, subthreshold binge eaters, or
      nonbingers by last observation carried forward (LOCF) method were not
      significant. At the end of treatment, the subthreshold binge eaters had the
      greatest weight loss. Although their binge eating and mood significantly
      improved, binge eaters and subthreshold binge eaters still had significant
      pathology in eating behaviors at completion of the program. CONCLUSION:
      Alternative treatment strategies focusing on disordered eating behaviors are
      needed to supplement standard dietary management of overweight treatment-seeking
      binge eaters.

PMID- 15507256
TI  - The identification of empirically derived cancer patient subgroups using
      psychosocial variables.
AB  - OBJECTIVE: To determine if there are subgroups of cancer patients who differ on
      coping, psychological, and quality of life (QOL) measures, and to determine if
      these subgroups have a different course of distress and health following a cancer
      diagnosis. METHODS: Three hundred fifty-one individuals presenting to a
      multidisciplinary melanoma clinic completed a baseline questionnaire packet
      containing the Brief Symptom Inventory (BSI), the Medical Outcomes Survey Short
      Form 36 (SF-36), Ways of Coping (WOC), State-Trait Anxiety Inventory (STAI), an
      informed consent form, and a demographic questionnaire. Participants subsequently
      completed measures at 2, 5, and 9 months after completion of their baseline
      assessment. A k-means cluster analysis was conducted using the subscales of the
      STAI, SF-36, and WOC. RESULTS: Four distinct clusters, psychologically unhealthy,
      physically unhealthy, combined psychologically and physically unhealthy, and
      healthy, were identified. These clusters differed on the General Severity Index
      (GSI) of the BSI and the General Health scale of the SF-36 at each of the four
      assessment points. The course of distress and general health was distinct for
      each cluster during the study, with combined and psychologically unhealthy
      clusters having greater levels of distress and combined and physically unhealthy
      clusters having poorer overall health. CONCLUSIONS: The findings from this study
      provide support for distinct subgroups of patients presenting with a diagnosis of
      cancer whose level of distress and general health vary greatly following a cancer
      diagnosis. Clinical interventions tailored to the level of psychological or
      physical impairment as determined by the cluster may result in better outcomes
      following cancer treatment.

PMID- 15507257
TI  - Development of the Korean version of the Geriatric Depression Scale and its short
      form among elderly psychiatric patients.
AB  - OBJECTIVE: The aim of this study was to evaluate the diagnostic validity of the
      Korean version of the Geriatric Depression Scale (GDS-K) and its short form among
      elderly psychiatric patients. METHOD: After three preliminary trials, the authors
      translated the GDS, including the Geriatric Depression Scale-Short Form (SGDS)
      into Korean. The GDS-K, the Korean version of the SGDS (SGDS-K), Hamilton Rating
      Scale for Depression (HRS-D), and the Center for Epidemiologic Studies Depression
      Scale (CES-D) were administered to 154 elderly psychiatric patients. In addition,
      the Diagnostic Interview Schedule (DIS-III-R) was administered independently to
      diagnose DSM-III-R major depression. Reliability and validity test, optimal
      cutoff point estimation, and receiver operating characteristics (ROC) curve
      analysis were performed to investigate the diagnostic validity of the GDS-K and
      SGDS-K. RESULTS: Internal consistency-reliability and concurrent validity of the
      GDS-K and SGDS-K associated with other depression scales (HRS-D, CES-D) were
      excellent. Content validity and discriminant validity, which differentiate DSM
      III-R major depression from nonmajor depression was also good. We suggest a score
      of 16 as the optimal cutoff point of GDS-K for screening DSM-III-R major
      depression among clinical populations and a score of 8 as optimal cutoff score of
      SGDS-K. ROC curve analysis indicated high diagnostic validity for both GDS-K and
      SGDS-K in assessing DSM-III-R major depression. Moreover, we found that the GDS-K
      and SGDS-K were highly correlated (r=.9522). This finding suggests that the SGDS
      K can be used as an adequate substitute for the GDS-K. CONCLUSION: The GDS-K and
      SGDS-K proved valid and reliable case-finding tools for screening DSM-III-R major
      depression among the elderly psychiatric patients in Korea. The relatively high
      cutoff points of both the GDS-K and SGDS-K require further evaluation from the
      viewpoint of culturally determined response style in elderly Koreans.

PMID- 15507258
TI  - Determinants of complaint symptoms in a Swedish health care practice--results of
      a questionnaire survey.
AB  - OBJECTIVE: The aim of this study was to identify predictors of complaint symptoms
      in an adult general practice population. METHOD: The study was performed in 1055
      out of 1442 consecutive adult patients visiting a Swedish health care centre. The
      relationship between complaint symptoms and sociodemographic characteristics,
      perceived health, and chronic disease was assessed using multiple regression
      analysis. RESULTS: Gender and perceived health were related to all symptom
      categories independently of each other, and when the effects of various symptom
      categories were taken into account in the regression analysis, the depression and
      tension symptom categories could predict about 50% of the explanation.
      CONCLUSION: The results of this study suggest that psychiatric symptoms,
      particularly depression and tension symptoms, interact and have an impact on
      somatic symptom reporting in addition to sociodemographic characteristics,
      perceived health, and chronic disease, which have impact on only some symptom
      categories.

PMID- 15507259
TI  - A systematic review and meta-analysis of the incidence and severity of
      postoperative fatigue.
AB  - OBJECTIVE: Postoperative fatigue is common following major abdominal surgery.
      Less is known about its prevalence in other surgical subgroups, and about its
      long-term prognosis. A systematic review of prospective cohort studies was
      conducted to clarify these issues. METHOD: Studies were identified from an
      extensive literature search. Overall estimates of pre- to postoperative change in
      fatigue severity and the incidence of clinically significant postoperative
      fatigue were calculated using meta-analyses. RESULTS: Eighty-one cohorts were
      identified. Type of surgery was found to be a possible predictor of fatigue
      severity, with major abdominal, gynaecological, cardiac and minor surgery
      apparently associated with greater fatigue than orthopaedic surgery. Limited data
      were available regarding the long-term persistence of postoperative fatigue.
      CONCLUSION: Postoperative fatigue appears to be an important problem following
      only certain forms of surgery. Why this is so remains unclear, and further work
      using better fatigue questionnaires is now required to confirm these differences.

PMID- 15507260
TI  - B cell biology, apoptosis, and autoantibodies to phospholipids.
AB  - Systemic autoimmune diseases are characterised by the development of a relatively
      narrow spectrum of autoantibodies. These are of considerable diagnostic value. In
      addition, in some diseases, including anti-phospholipid syndrome, these
      autoantibodies can be directly pathogenic. Understanding how these autoantibodies
      are formed represents an important avenue towards understanding the pathogenesis
      of systemic autoimmune disease itself. The minimum requirements for production of
      autoantibodies are self-reactive B cells and the availability of autoantigen. In
      other words, their formation is determined by factors that shape the B cell
      repertoire and the distribution and immunogenicity of the relevant autoantigens.
      On the B cell side, the propensity to produce autoantibodies depends on the
      fidelity of B cell self-tolerance mechanisms, B cell differentiation and
      selection into different peripheral compartments. These processes are
      interdependent, because both selection into different peripheral and mechanisms
      of B cell self-tolerance are influenced by signalling through the B cell receptor
      (BCR). On the antigen supply side, apoptotic cells appear to be a crucial source
      of antigenic targets of systemic autoimmunity, and elaborate mechanisms exist to
      ensure that apoptotic corpses undergo efficient disposal and do not become
      immunogenic. Several defects have been described where the disposal of apoptotic
      cells is compromised leading to their accumulation in parenchymal organs. These
      may become immunogenic resulting in autoantibody formation. The mechanisms that
      lead to progression from accumulation of autoantigen, in the form of apoptotic
      corpses, to the production of autoantibodies by self-reactive B cells within
      different parts of the peripheral repertoire are discussed.

PMID- 15507261
TI  - The impact of the inflammatory response on coagulation.
AB  - Inflammation contributions to the thrombotic response involve both cellular and
      humoral modulation. Inflammation impacts the initiation, propagation and the
      inhibitory phases of blood coagulation. Inflammatory mediators like endotoxin and
      tumor necrosis factor alpha (TNF alpha) elicit the expression of tissue factor on
      blood cells. Under normal circumstance, negatively charged membrane surfaces are
      limiting so that, even if some activated coagulation factors are generated,
      propagation of the coagulant stimulus is minimal. Complement activation, however,
      or exposure of collagen in combination with thrombin, provides a potent stimulus
      eliciting the exposure of negatively charged phospholipid membrane surfaces.
      Natural anticoagulant mechanisms limit the thrombotic response, but these
      pathways are depressed by inflammatory mediators. The protein C pathway is one of
      the major targets. Thrombomodulin and the endothelial cell protein C receptor are
      both required for optimal protein C activation, but both are down regulated by
      inflammatory mediators. Furthermore, free protein S levels often decrease
      resulting in impaired anticoagulant function of the activated protein C that is
      generated. In addition, anti-phospholipid antibodies severely impair the protein
      C pathway further inhibiting this pathway in inflammatory states associated with
      auto-immunity. In addition to shifting the hemostatic system in favor of clot
      formation, inflammation elevates the levels of plasminogen activator inhibitor
      thereby decreasing fibrinolytic activity. The procoagulant impact of inflammation
      can also be seen at the cellular level. Inflammatory mediators like interleukin 6
      can increase both platelet count and their responsiveness to agonists like
      thrombin. All of these events tend to shift the hemostatic balance in favor of
      clot formation.

PMID- 15507262
TI  - Inflammatory response and the endothelium.
AB  - Antiphospholipid-mediated endothelium perturbation plays a role in
      antiphospholipid syndrome (APS)-associated vasculopathy. Antiphospholipid
      antibodies activate endothelium both in vitro and in vivo experimental models by
      inducing a pro-inflammatory/-coagulant phenotype; the antibodies recognize beta2
      glycoprotein I (beta2GPI) on human endothelial cells (EC) from different parts of
      the vasculature. In spite of such large in vitro evidence, few studies have
      addressed the issue whether or not a comparable endothelial perturbation might be
      detectable in vivo. We investigated several indirect ex vivo parameters of
      endothelial dysfunction: plasma levels of soluble adhesion molecules (sADM),
      soluble thrombomodulin (sTM), von Willebrand factor (vWF) and tissue plasminogen
      activator (t-PA) by solid-phase assays. The study included: patients with primary
      antiphospholipid syndrome (n=32), with the syndrome secondary to non-active
      systemic lupus erythematosus (SLE, n=10), six patients with persistent
      antiphospholipid positivity at medium/high titre without any clinical
      manifestation of the syndrome. Fifty-two age and sex matched healthy subjects
      have been enrolled as controls. In addition, circulating endothelial cells
      identified by flow cytometry and the brachial artery flow-mediated vasodilation
      (FMV) were evaluated in 26 patients (20 primary and 6 lupus syndromes) and 30
      healthy controls. Plasma levels of soluble adhesion molecules did not differ from
      controls, while a significant increase in von Willebrand factor titres (P<0.05)
      was found. No significant difference was found regarding the number of
      circulating endothelial cells and flow-mediated vasodilation. As a whole, these
      findings do suggest that antiphospholipid antibodies per se are not able to
      support a full-blown endothelial perturbation in vivo. As shown in
      antiphospholipid syndrome experimental animal models, a two-hit hypothesis is
      suggested.

PMID- 15507263
TI  - Beta 2 glycoprotein I--function in health and disease.
AB  - Beta-2 glycoprotein I (beta2GPI) is the principal target of autoantibodies in the
      antiphospholipid syndrome (APS). It is abundant in human plasma and shares high
      homology between different mammalian species. Although the exact physiological
      function of beta2GPI has not been fully elucidated, several interactions have
      been described with other proteins and with negatively charged surfaces, such as
      anionic phospholipids, dextran and heparin. beta2GPI is involved in the
      coagulation pathway, exerting both procoagulant and anticoagulant activities.
      Plasma from beta2GPI-deficient mice exhibits impaired thrombin generation in
      vitro. Recently, it has been demonstrated that beta2GPI binds factor (F) XI in
      vitro at concentrations lower than those of the protein in human plasma, and this
      binding inhibits FXI activation to FXIa by thrombin and FXIIa. Proteolytic
      cleavage of the fifth domain of beta2GPI abolishes its inhibition of FXI
      activation and results in reduced ability of the cleaved beta2GPI to bind
      phospholipids. It retains its ability to bind FXI. In vivo activation of FXI by
      thrombin is thought to be an important mechanism by which coagulation is
      accelerated via components of the contact activation pathway. Thus beta2GPI may
      attenuate the contact activation pathway by inhibiting activation of FXI by
      thrombin. Moreover, because beta2GPI is the dominant autoantigen in patients with
      APS, dysregulation of this pathway by autoantibodies may be an important
      mechanism for thrombosis in patients with APS.

PMID- 15507264
TI  - Beta2-glycoprotein I: antiphospholipid syndrome and T-cell reactivity.
AB  - There is increasing evidence showing that recurrent thrombosis and intrauterine
      fetal loss in antiphospholipid syndrome (APS) are attributable to
      antiphospholipid (aPL) antibodies. We have recently identified autoreactive CD4+
      T cells to beta2-glycoprotein I (beta2GPI) that promote production of pathogenic
      antiphospholipid antibodies. beta2GPI-specific CD4+ T cells preferentially
      recognize the antigenic peptide containing the major phospholipid (PL)-binding
      site in the context of DR53. T-cell helper activity that stimulates B cells to
      produce IgG anti-beta2GPI antibodies is mediated through IL-6 and CD40-CD154
      interaction. beta2GPI-specific T cells respond to reduced beta2GPI and
      recombinant beta2GPI fragments produced in a bacterial expression system but not
      to native beta2GPI, indicating that the epitopes recognized by beta2GPI-specific
      T cells are 'cryptic' determinants, which are generated at a subthreshold level
      by the processing of native beta2GPI under normal circumstances. Although
      beta2GPI-specific T cells are detected in both APS patients and healthy
      individuals, these autoreactive T cells are activated in vivo in APS patients but
      not in healthy individuals. These findings indicate activation of beta2GPI
      specific T cells and subsequent production of pathogenic anti-beta2GPI antibodies
      can be induced by the exposure of such T cells to cryptic peptides of beta2GPI
      efficiently presented by functional antigen-presenting cells (APC). Delineating
      the mechanisms that induce the efficient processing and presentation of cryptic
      determinants of beta2GPI as a consequence of antigen processing would clarify the
      etiology that initiates the autoantibody response in APS.

PMID- 15507265
TI  - Primary, Secondary, Catastrophic Antiphospholipid Syndrome: is there a
      difference?
AB  - Following broad recognition of the disorder called Antiphospholipid Syndrome
      (APS), it has come to be subcategorized into Primary (PAPS), Secondary (SAPS),
      and Catastrophic Antiphospholipid Syndrome (CAPS). Primary utilized when there is
      no associated disorder, secondary with an associated autoimmune disorder such as
      systemic lupus erythematosus (SLE), and "catastrophic" when thrombosis occurs at
      multiple sites in a short space of time. Are these entities different? Such
      differences should be demonstrated in terms of their clinical presentation,
      disease course, pathogenesis, or management. If no differences exist, is there a
      basis for continued use of these terms? This manuscript will attempt to explore
      distinctions between subgroups of the APS and reasons for or against perpetuation
      of these classifications in the literature.

PMID- 15507266
TI  - The antiphospholipid syndrome as a model for B cell-induced autoimmune diseases.
AB  - Growing awareness of the pathophysiological importance of B cells for
      antiphospholipid antibody syndrome (APS), particularly those expressing the T
      cell marker CD5, has recently led to the proposal that their tolerance may be
      used as a method to reduce specific antibody (Ab) production. B cell tolerance
      has indeed become one of the most exciting developments in the treatment of this
      disease. Based on their production of multispecific Ab, these CD5+ B lymphocytes,
      also referred to as B-1 cells, are thought to account for most of the AutoAb in
      autoimmune murine models. Raised numbers of circulating CD5+ B cells correlate
      with high levels of anti-phospholipid (PL) Ab in some APS patients, and
      participate in altered immunity of women with recurrent spontaneous abortion.
      These findings are not surprising in view of the cross-reaction with PL of anti
      bromelain-treated erythrocyte Ab secreted by these cells. Transgenic animals
      have, however, shown that B lymphocytes contribute to such disorders through a
      variety of characteristics other than Ab production. Indeed, owing to the role of
      the CD5 molecule in the maintenance of clonal anergy, increased proportions of B
      1 cells may merely reflect their defective regulation through CD5 itself. Various
      B cell receptor (BCR)-associated transmembrane glycoproteins are also involved in
      the behavior of the cells. These include CD19 which amplifies the message, and
      CD22 which dampens down the BCR signaling. In addition, B lymphocytes may act as
      potent antigen-presenting cells for autoantigens, all the more because they
      secrete an excess of autocrine-acting interleukin-10 in autoimmune states.
      Furthermore, by modifying the specificity of their BCR, not only in the bone
      marrow, but also in the secondary lymphoid organs, autoreactive B cells may
      initiate new immunoglobulin rearrangements. It is interesting that self-reactive
      Ab-making cells present with such rearrangements. Finally, B cells have the
      capacity to polarize into B effector (Be)-1 and Be-2, with different cytokine
      patterns that regulate the levels of T helper (Th)-1 and Th-2, respectively. Such
      a cytokine might be defective in nonorgan-specific autoimmune diseases. In
      conclusion, B lymphocytes are required for the initiation of anti-self Ab
      associated disorders, such as APS. Their classical view in the biology of immune
      responses to self as autoAb secreting cells turns out to be rather naive, and an
      essential role for B lymphocytes may not be producing autoAb.

PMID- 15507267
TI  - Anti-phospholipid antibodies (aPL) and apoptosis: prothrombin-dependent aPL as a
      paradigm for phospholipid-dependent interactions with apoptotic cells.
AB  - The natural targets of anti-phospholipid antibodies (aPL) and the stimuli that
      induce them remain unknown. Apoptotic cells have been proposed as both potential
      targets and immunogens for anti-phospholipid antibodies. Demonstration of
      selective recognition by anti-phospholipid antibodies provides support for
      apoptotic cells as antigenic targets. Here, we summarize data showing that
      prothrombin (PT) binds to apoptotic, but not viable, cells, and that apoptotic
      cell bound prothrombin provides a target for human polyclonal and murine
      monoclonal lupus anticoagulant (LA) antibodies. We discuss findings for two
      monoclonal lupus anticoagulant antibodies that have high (antibody 29J3-62) or
      low (antibody 29I4-24) affinity, respectively, for soluble prothrombin. Despite
      their very different affinities for soluble prothrombin, both monoclonal
      antibodies reacted similarly with prothrombin bound to phospholipid or apoptotic
      cells. Furthermore, both antibodies enhanced the binding of prothrombin to
      apoptotic cells. We propose that the recognition of apoptotic cells by these
      prothrombin-dependent monoclonal antibodies provides a paradigm for other anti
      phospholipid autoantibodies. 29I4-24 is prototypical of phospholipid-dependent
      anti-phospholipid antibodies, while 29J3-62 represents a prototype for
      phospholipid-independent anti-phospholipid antibodies. Proteins such as
      prothrombin and beta2-glycoprotein I (beta2GPI) bind to apoptotic cells, thereby
      enhancing the recognition of apoptotic cells by anti-phospholipid antibodies.
      Furthermore, anti-phospholipid antibodies potentiate the interaction of these
      proteins with apoptotic cells. While it is unclear whether apoptotic cells are
      the inducing stimuli in patients with anti-phospholipid antibodies or even
      whether anti-phospholipid antibodies interact with apoptotic cells in vivo, it is
      nonetheless clear that anti-phospholipid antibodies have the potential to affect
      both the procoagulant activity and the uptake and clearance of apoptotic cells.

PMID- 15507269
TI  - Mechanisms of autoantibody-induced monocyte tissue factor expression.
AB  - The expression of tissue factor (TF) activity to flowing blood is the trigger for
      physiological coagulation as well as many types of thrombosis. A growing body of
      evidence suggests that increased tissue factor activity is a significant
      contributor towards the hypercoagulability associated with the antiphospholipid
      syndrome (APS). The increase in tissue factor activity appears to be due to
      increased transcription and translation of nascent tissue factor molecules but is
      not due to de-encryption of existing tissue factor molecules on cells.
      Autoantibodies and/or immune complexes circulating in APS patients appear to
      enhance the expression of tissue factor activity on monocytes and endothelial
      cells. Anti-beta2-glycoprotein I (beta2GPI) autoantibodies have been specifically
      implicated in the antibody-mediated enhancement of tissue factor activity. The
      presence of antibodies against tissue factor pathway inhibitor (TFPI) in certain
      APS patients suggests that negative regulation of tissue factor activity might
      also be impaired in these patients. Given a mechanism involving increased tissue
      factor activity in APS-associated thrombosis, agents specifically targeting
      tissue factor activity may be a novel and efficacious therapy that is safer than
      current approaches to the management of APS.

PMID- 15507268
TI  - Antibody-mediated interference with annexins in the antiphospholipid syndrome.
AB  - Targeting of the annexin A5 anticoagulant shield may be a significant mechanism
      for thrombosis and pregnancy losses in APS. This may occur via high affinity
      antibodies that recognize phospholipid-binding proteins that are capable of
      interfering with the assembly of the annexin A5 shield on phospholipid surfaces
      or via direct recognition of annexin A5 by autoantibodies. In addition,
      antibodies against other members of the annexin family of proteins may also have
      pathogenic roles in APS. It is anticipated that further research will elucidate
      the biologic functions of these proteins and their roles in the aPL disease
      processes.

PMID- 15507270
TI  - Growth and function of the normal human placenta.
AB  - The placenta is the highly specialised organ of pregnancy that supports the
      normal growth and development of the fetus. Growth and function of the placenta
      are precisely regulated and coordinated to ensure the exchange of nutrients and
      waste products between the maternal and fetal circulatory systems operates at
      maximal efficiency. The main functional units of the placenta are the chorionic
      villi within which fetal blood is separated by only three or four cell layers
      (placental membrane) from maternal blood in the surrounding intervillous space.
      After implantation, trophoblast cells proliferate and differentiate along two
      pathways described as villous and extravillous. Non-migratory, villous
      cytotrophoblast cells fuse to form the multinucleated syncytiotrophoblast, which
      forms the outer epithelial layer of the chorionic villi. It is at the terminal
      branches of the chorionic villi that the majority of fetal/maternal exchange
      occurs. Extravillous trophoblast cells migrate into the decidua and remodel
      uterine arteries. This facilitates blood flow to the placenta via dilated,
      compliant vessels, unresponsive to maternal vasomotor control. The placenta acts
      to provide oxygen and nutrients to the fetus, whilst removing carbon dioxide and
      other waste products. It metabolises a number of substances and can release
      metabolic products into maternal and/or fetal circulations. The placenta can help
      to protect the fetus against certain xenobiotic molecules, infections and
      maternal diseases. In addition, it releases hormones into both the maternal and
      fetal circulations to affect pregnancy, metabolism, fetal growth, parturition and
      other functions. Many placental functional changes occur that accommodate the
      increasing metabolic demands of the developing fetus throughout gestation.

PMID- 15507271
TI  - Haemostatic changes in pregnancy.
AB  - In normal pregnancy, there is a marked increase in the procoagulant activity in
      maternal blood characterized by elevation of factors VII, X, VIII, fibrinogen and
      von Willebrand factor, which is maximal around term. This is associated with an
      increase in prothrombin fragments (PF1+2) and thrombin-antithrombin complexes.
      There is a decrease in physiological anticoagulants manifested by a significant
      reduction in protein S activity and by acquired activated protein C (APC)
      resistance. The overall fibrinolytic activity is impaired during pregnancy, but
      returns rapidly to normal following delivery. This is largely due to placental
      derived plasminogen activator inhibitor type 2 (PAI-2), which is present in
      substantial quantities during pregnancy. D-dimer, a specific marker of
      fibrinolysis resulting from breakdown of cross-linked fibrin polymer by plasmin,
      increases as pregnancy progresses. Overall, there is a 4- to 10-fold increased
      thrombotic risk throughout gestation and the postpartum period. Local haemostasis
      at the placental throphoblast level is characterized by increased tissue factor
      (TF) expression and low expression of the inhibitor TFPI. Microparticles derived
      from maternal endothelial cells and platelets, and from placental throphoblasts
      may contribute to the procoagulant effect. Local anticoagulant mechanisms on
      placental throphoblasts are important for counterbalance of the procoagulant
      milieu. Disruption of anticoagulant mechanisms, for example, autoantibodies, to
      annexin V may increase pregnancy complications in patients with antiphospholipid
      antibodies (APLA).

PMID- 15507272
TI  - Antiphospholipid antibodies and fetal compromise.

PMID- 15507273
TI  - Treatment of antiphospholipid syndrome in pregnancy--a systematic review of
      randomized therapeutic trials.
AB  - A comprehensive literature search identified 13 randomized or quasi-randomized
      therapeutic trials of obstetric antiphospholipid syndrome (aPL) syndrome and all
      but one are appraised. Several overriding problems with trial design were
      evident: (i) small trial size, (ii) absence of blinding, (iii) lack of no
      treatment arms and (iv) highly variable entry criteria, treatments and endpoint
      definitions leading to trial clinical heterogeneity. Low-dose aspirin and heparin
      is recommended for obstetric antiphospholipid syndrome but the evidentiary basis
      for this remains weak. There is no evidence to support treatment with intravenous
      immunoglobulin or prednisone. Ideally, co-operative large fully blinded placebo
      controlled randomized trials of therapy in patients with obstetric aPL stratified
      by different levels of risk are still required.

PMID- 15507274
TI  - Immunologic manipulation for the threatened fetus.
AB  - Management of the pregnant woman with the antiphospholipid syndrome (APLS) has
      improved over the last 10 years. The recurrent pregnancy loss that is associated
      with this disease is managed with prophylactic low dose aspirin and heparin
      therapy. This therapy leads to a 40% absolute risk reduction in pregnancy loss.
      However, many women still fail to deliver a live infant despite this therapy so
      immunologic manipulation of the mother's disease in this group needs to be
      considered. Intravenous immunoglobulin and plasma exchange may have a role. New
      immunosuppressive drugs such as tacrolimus have yet to be tried. Monoclonal
      antibodies to B cells, B-cell growth factors, complement proteins and integrin
      molecules, all of which appear to play a role in the disease process, may also
      offer patients some hope. Similarly, biologics such as C1 esterase inhibitor
      protein, cell surface complement regulator proteins or interleukin-3 need to be
      tried given their efficacy in models of antibody-induced cell injury.

PMID- 15507275
TI  - How much warfarin is enough in APS related thrombosis?
AB  - Warfarin is the best available, most effective treatment for the secondary
      prevention of recurrent thrombosis in antiphospholipid syndrome (APS) patients.
      However, warfarin is cumbersome for both patients and physicians because of risk
      for bleeding and the need for frequent monitoring. Much detail regarding optimal
      management of APS patients still lacks an evidence-based approach. Asymptomatic
      patients should not receive warfarin. An optimal treatment for patients with
      livedo, cardiac valve disease, leg ulcers or microangiopathic nephropathy is
      unknown; it is likely that warfarin is ineffective for these manifestations of
      the APS. In low risk patients who have not previously failed warfarin, moderate
      intensity anticoagulation (target international normalized ratio [INR] 2.5) is as
      effective as, and safer than, high intensity anticoagulation (INR 3.5), at least
      for patients with venous thrombosis. Current recommendations, based on the
      opinion rather than on documentation, state that warfarin should be prescribed
      for the APS patient's life; studies that challenge this conclusion for carefully
      defined low risk patients whose thromboses occurred with trigger events will be
      welcome, as will be studies examining alternatives to warfarin, including
      antiplatelet drugs.

PMID- 15507276
TI  - Anticoagulant therapy for the thrombotic complications of the antiphospholipid
      antibody syndrome.
AB  - Patients with antiphospholipid antibodies (APLA) are at risk of arterial
      thromboembolism (ATE) or venous thromboembolism (VTE). The true strength of the
      association between APLA and first TE is unknown as there are no prospective
      studies of a large, well-characterized inception cohort of matched patients with
      and without APLA. Thus, evidence-based treatment recommendations for primary
      prophylaxis of TE in such patients cannot be made. Optimal therapy of patients
      with recent TE and APLA remains controversial; although there is no doubt that
      some such patients have a malignant hypercoagulable state characterized by
      resistance to "usual intensity" anticoagulation; recent evidence suggests that
      most such patients are adequately treated with "usual therapy". After warfarin
      discontinuation, such patients appear to be at increased risk of recurrent TE, as
      demonstrated in a series of studies of discontinuation of secondary TE
      prophylaxis in patients with APLA and venous TE (VTE). Because of this increased
      risk of recurrent TE, after anticoagulants are discontinued, most "experts"
      recommend extended duration therapeutic dose warfarin for such patients. This
      paper will briefly review this evidence.

PMID- 15507277
TI  - Platelet physiology and thrombosis.
AB  - Glycoprotein (GP) Ibalpha of the GPIb-IX-V complex and GPVI bind von Willebrand
      factor (vWF) and collagen, respectively, and are critical for the initial
      interaction of circulating platelets with the injured vessel wall under high
      shear conditions. These interactions act together to facilitate stable thrombus
      formation in vivo. Ligand binding to GPIb-IX-V of the leucine-rich repeat family
      or GPVI of the immunoglobulin superfamily initiates platelet activation, and
      inside-out activation of the platelet integrin, alphaIIbbeta3, that binds vWF or
      fibrinogen and mediates platelet aggregation. The binding site for GPIbalpha on
      vWF resides in the conserved A1 domain, encompassing the disulfide bond at Cys509
      Cys695. This domain may be activated to bind platelet GPIbalpha under shear
      stress by anchoring of the downstream A3 domain to collagen and conformational
      distortion of the intervening A2 domain. The N-terminal, 282 residues, of
      GPIbalpha contains the binding site for vWF-A1, as well as the conserved A-type
      domain of the leukocyte integrin alphaMbeta2 (alphaM I domain) and P-selectin
      expressed on activated platelets or endothelial cells. Endothelial P-selectin
      also supports surface expression of vWF multimers, enabling platelet vessel wall
      interaction by at least two mechanisms. Recent evidence suggests GPVI that binds
      collagen, and GPIb-IX-V that binds collagen-bound vWF are physically associated
      on the platelet surface. This review will focus on the structure-function of
      primary platelet adhesion receptors, GPIb-IX-V and GPVI, and how they act
      together to regulate platelet thrombus formation in pathophysiology.

PMID- 15507278
TI  - Beta2-glycoprotein I and LDL-receptor family members.
AB  - The presence of antiphospholipid antibodies in plasma is a risk factor for
      thrombo-embolic complications. In vitro, however, the same antibodies can prolong
      clotting times in coagulation assays, a classic marker for a bleeding tendency.
      For years this contradiction puzzles many scientists.We now know that the term
      antiphospholipid antibodies comprises a heterogeneous population of antibodies
      and there is growing evidence that only subpopulations of antiphospholipid
      antibodies are relevant for the clinical complication. In combination with new
      information on the complex interaction between antiphospholipid antibodies, the
      protein beta2-Glycoprotein I, and cellular surfaces have opened new avenues for
      the understanding of the pathology of this syndrome.

PMID- 15507279
TI  - Beta2-glycoprotein I, anti-beta2-glycoprotein I, and fibrinolysis.
AB  - Beta2-glycoprotein-I (beta2GPI) is a phospholipid-binding plasma protein that
      consists of five homologous domains. Domain V is distinguished from others by
      bearing a positively charged lysine cluster and hydrophobic extra C-terminal
      loop. Beta2GPI has been known as a natural anticoagulant regulator. Beta2GPI
      exerts anticoagulant activity by inhibition of phospholipid-dependent coagulation
      reactions such as prothrombinase, tenase, and factor XII activation. It also
      binds factor XI and inhibits its activation. On the other hand, beta2GPI inhibits
      anticoagulant activity of activated protein C. According to the data from
      knockout mice, beta2GPI may contribute to thrombin generation in vivo.
      Phospholipid-bound beta2GPI is one of the major target antigens for
      antiphospholipid antibodies present in patients with antiphospholipid syndrome
      (APS). Binding of pathogenic anti-beta2GPI antibodies increases the affinity of
      beta2GPI to the cell surface and disrupts the coagulation/fibrinolysis balance on
      the cell surface. These pathogenic antibodies activate endothelial cells via
      signal transduction events in the presence of beta2GPI. Impaired fibrinolysis has
      been reported in patients with APS. Using a newly developed chromogenic assay, we
      demonstrated lower activity of intrinsic fibrinolysis in euglobulin fractions
      from APS patients. Addition of monoclonal anti-beta2GPI antibodies with beta2GPI
      also decreased fibrinolytic activity in this assay system. beta2GPI is
      proteolytically cleaved by plasmin in domain V (nicked beta2GPI) and becomes
      unable to bind to phospholipids, reducing antigenicity against antiphospholipid
      antibodies. This cleavage occurs in patients with increased fibrinolysis
      turnover. Nicked beta2GPI binds to plasminogen and suppresses plasmin generation
      in the presence of fibrin, plasminogen, and tissue plasminogen activator (tPA).
      Thus, nicked beta2GPI plays a role in the extrinsic fibrinolysis via a negative
      feedback pathway loop.

PMID- 15507280
TI  - Intracellular signaling triggered by antiphospholipid antibodies in platelets and
      endothelial cells: a pathway to targeted therapies.
AB  - Understanding the intracellular events triggered by antiphospholipid (aPL)
      antibodies in platelets and endothelial cells (ECs) is important in designing new
      modalities of targeted therapies for the treatment of thrombosis in
      Antiphospholipid Syndrome (APS). A recent study showed a significant increase in
      the expression of GPIIb/IIIa on platelets treated with aPL antibodies and a
      thrombin receptor peptide agonist (TRAP), and these effects were abrogated by
      hydroxychloroquine (HQ). Hydroxychloroquine has also been shown to reduce in vivo
      aPL-induced thrombus formation. Furthermore, aPL-enhanced thrombosis in vivo can
      be abrogated by infusions of a GPIIb/IIIa antagonist (1B5) monoclonal antibody,
      and aPL-mediated thrombophilia is not observed in GPIIb/IIIa-deficient mice.
      Treatment of platelets with aPL antibodies has resulted in a significant increase
      in p38 mitogen-activated protein kinase (p38MAPK) phosphorylation and aPL-induced
      platelet aggregation and thromboxane B2 (TXB2) production was abrogated by
      SB203580 (a p38MAPK inhibitor). aPL antibodies induce increased expression,
      function and transcription of tissue factor (TF) on EC. Activation of ECs and
      thrombogenicity of aPL in vivo can be reversed by treatment of the animals with
      statins. Upregulation of TF on ECs can also be abrogated by treatment of the
      cells with fluvastatin. There is also indication of activation of nuclear factor
      kappa B (NFkappaB), increase in phosphorylation of p38MAPK in ECs by aPL
      antibodies that can be reversed by specific inhibitors MG132 and SB203580,
      respectively. The data open the possibility to new treatment modalities that may
      include the use of hydroxychloroquine, statins, specific antagonists of
      GPIIb/IIIa (such as abciximab or equivalent) and specific p38MAPK inhibitors,
      after the completion of well-designed clinical studies.

PMID- 15507281
TI  - The interface of multiple sclerosis and antiphospholipid antibodies.
AB  - The interface between multiple sclerosis (MS) and the antiphospholipid syndrome
      (APS) is of great clinical relevance and may also shed some light on their
      pathogenesis. Although formal diagnostic criteria of these two immune syndromes
      are ostensibly mutually exclusive, many patients with subcortical white matter
      brain lesions share features of both MS and APS. The main diagnostic feature of
      APS, the antiphospholipid antibodies (aPLAb), is relatively common in multiple
      sclerosis and increased fibrin deposition is a feature of both APS lesions and MS
      plaques. A closer examination of the clinical and laboratory data reveals,
      however, fundamental differences between the syndromes: MS is a diffuse disease
      of white matter compared to a much more patchy disease in APS as demonstrated by
      recent studies in imaging and electrophysiology. Furthermore, a closer
      examination of the specific aPLAb profile reveals significant differences: we
      have found that although aPLAb were common in MS patients (32%), these antibodies
      did not depend on the presence of serum factors for binding to phospholipids and
      none of the MS patients had antibodies to beta2-glycoprotein-I (beta2-GPI), the
      major autoantigen in APS. Animal models of the two syndromes are induced by very
      different antigens and may serve to assess overlapping pathogenic mechanisms. The
      most common treatment used in MS are beta-interferons which theoretically may
      exacerbate APS, while anticoagulation, the mainstay of APS treatment, is of
      unknown value in MS. The relationship of MS to APS remains to be clarified by
      focused large collaborative studies.

PMID- 15507282
TI  - Controversies in the antiphospholipid syndrome and stroke.
AB  - Many clinicians providing care and advice to patients with antiphospholipid
      syndrome (APS), where the principal clinical manifestation is stroke, do so in
      the setting of an evidence base of mixed quality. Indeed, systematic studies have
      not particularly helped the practising clinician as they have been characterised
      by variable criteria used to select subjects, making it impossible to extrapolate
      to typical clinic patients. This has left us with a number of key questions, each
      of which attracts controversy in terms of patient management. In this review,
      these are posed as a series of questions with the answer, or lack of one,
      considered after each question. The review draws attention to the important
      questions that require answers for current primary and secondary prevention, as
      well as treatment of APS and stroke, and suggests a series of studies that are
      needed to clarify these issues.

PMID- 15507283
TI  - Management of the neurological manifestations of APS--what do the trials tell us?
AB  - PURPOSE: To systematically review evidence from clinical trials about the
      management of neurological manifestations of Antiphospholipid Syndrome (APS).
      METHODS: Articles reporting case-control, cohort and prospective studies and
      treatment trials of primary or secondary stroke prevention in patients with aPL
      were identified in an OVID literature search from 1966 to 2004, using the
      keywords: APS, aPL and cerebrovascular disease. Articles were evaluated according
      to the standard system for assessing medical evidence to answer the following
      questions: (1) What is the role of aPL and recurrent stroke risk in both primary
      and secondary APS populations? (2) What is the evidence to support specific
      treatment strategies for secondary prevention of aPL-associated stroke? (3) What
      is the evidence to support specific treatment strategies for primary prevention
      of aPL-associated stroke? CONCLUSIONS: (1) aPL are a risk factor for incident
      stroke (Grade A, established as useful for the given condition in the specified
      population). (2) The evidence to support the role of aPL in recurrent stroke is
      conflicting and, therefore, inconclusive. (3) Warfarin at moderate-intensity
      doses is equally effective in preventing a recurrent thrombotic event as warfarin
      at high-intensity doses in patients with APS (Grade A evidence, established as
      useful for the given condition in the specified population). (4) Warfarin, at
      moderate-intensity doses is as effective as aspirin (at a dose of 325 mg/day) in
      preventing recurrent thrombotic events in patients who are aPL-positive at the
      time of an initial stroke (Grade B evidence, probably useful for the given
      condition in the given population). (5) Currently there are no data to support
      the use of any prophylactic therapy in patients with aPL and no clinical
      manifestations for the purposes of preventing an incident stroke.

PMID- 15507284
TI  - Coronary and valvular syndromes and antiphospholipid antibodies.
AB  - Since the recognition of the antiphospholipid syndrome (APS), a large number of
      cardiac manifestations have been reported in association with these antibodies,
      including coronary artery and valvular disease, cardiomyopathy, and intracardiac
      thrombosis. Most of these manifestations are explicable on the basis of
      thrombotic lesions either in the coronary circulation or on the valves and may
      mimic other similar conditions, such as rheumatic fever or infectious
      endocarditis. The APS coagulopathy in these patients requires the careful and
      judicious use of appropriate antiaggregant and anticoagulant therapy. In this
      review article, the focus will be on the main cardiac features related to the
      presence of antiphospholipid antibodies (aPLs), which may be of interest to
      clinicians.

PMID- 15507285
TI  - Peripheral vascular disease in antiphospholipid syndrome.
AB  - Atherosclerosis has been considered an inflammatory disease based on the finding
      that atherosclerotic lesion contains activated T lymphocytes reacting with
      oxidized low-density lipoproteins (oxLDL) and heat shock proteins (HSP); it also
      contains autoantigens like beta2GPI, a target of antibodies occurring in an
      immune-mediated thrombophilia called antiphospholipid syndrome (APS). Further
      support to this hypothesis comes from the cross-reactivity, which occurs between
      antiphospholipid antibodies (aPL) and antibodies to oxLDL. Animal experiments
      have shown that aPL are associated with atheroma. In addition, accelerated
      atherosclerosis has been detected in patients with a prototype systemic
      autoimmune disease, such as systemic lupus erythematosus (SLE). However, the
      association of APS or aPL with atherosclerosis is a matter of debate due to the
      small numbers of patients studied, and the fact that traditional risk factors for
      atherosclerosis coexist. The prevalence of APS ranges from 1.7% to 6%, and that
      of aPL reaches to 14% among patients with peripheral vascular disease defined on
      the basis of clinical outcomes. On the other hand, the prevalence of asymptomatic
      atherosclerosis, defined in terms of plaques in ultrasonography, reaches to 15%
      of patients with APS compared to 9% of SLE patients and 3% of normal controls.
      Among SLE patients with aPL, the prevalence of plaques ranges from 6% in
      premenopausal women to 31% in unselected patients. Less than 10% of APS patients
      express premature atherosclerosis in the absence of other risk factors. Which APS
      patient will develop atherosclerosis is unpredictable.

PMID- 15507286
TI  - Tests for lupus anticoagulant revisited.

PMID- 15507287
TI  - Anti-beta2-glycoprotein I antibodies--when and how should they be measured?
AB  - The biological criteria of the antiphospholipid syndrome defined at the Sapporo
      meeting in 1998 included the presence of lupus anticoagulant (LA) and/or
      anticardiolipin antibodies at medium and high titers. During the 48th SSC meeting
      held in Boston July 2002, it was proposed to modify these criteria. Four patient
      groups were defined, the first one comprising LA and anti-beta2glycoprotein I
      antibodies (abeta2GPI), the second one LA only, the third one abeta2GPI only and
      the fourth one other antiphospholipid antibodies such as antiprothrombin,
      anticardiolipin, antiphosphatidylethanolamine, etc. This proposition raised the
      issue of the association of abeta2GPI with APS clinical criteria (thrombosis and
      pregnancy morbidity). In some studies, a strong association between IgG abeta2GPI
      and thrombosis was found, whereas in others this association could not be
      demonstrated. In the obstetrical field, few studies are available and no clear
      conclusion can be drawn yet. However, for thrombosis or pregnancy morbidity, it
      has been shown that in up to 10% of patients, abeta2GPI are the sole antibodies
      present and therefore the diagnosis of APS would be missed in these patients. In
      addition, some studies suggest that the severity of disease is dependent on the
      number of positive tests and on their titers. We recommend abeta2GPI assays to be
      included in the panel of antiphospholipid screening tests. However, the
      standardisation of abeta2GPI assays has to be improved in order to ensure better
      comparability between the studies.

PMID- 15507288
TI  - Antiprothrombin antibodies--are they worth assaying?
AB  - According to the preliminary classification criteria of the antiphospholipid
      syndrome (APS) (Sapporo Criteria), beta2-glycoprotein I (beta2GPI)-dependent
      anticardiolipin antibodies (aCL) and lupus anticoagulant (LA) are the only
      laboratory tests considered as criteria for the classification of the APS.
      Recently, antibodies against phosphatidylserine-prothrombin complex (aPS/PT) have
      been detected and these antibodies, rather than antibodies against prothrombin
      alone, are closely associated with APS and LA. We assessed the sensitivity and
      specificity of aPS/PT for the diagnosis of APS in our population of patients with
      a variety of autoimmune disorders and investigated whether aPS/PT could be used
      as diagnostic test in patients suspected of having APS. The study population
      comprised 219 patients with autoimmune diseases including 82 patients with APS
      and 137 without APS (55 systemic lupus erythematosus, 32 rheumatoid arthritis, 10
      primary Sjogren's syndrome, 8 scleroderma, 5 Behcet's disease and 27 other
      rheumatic diseases). IgG/M aPS/PT were measured by ELISA using phosphatidylserine
      prothrombin complex as antigen immobilized on ELISA plates in the presence of
      CaCl2. IgG/M aCL were measured by standard methods and LA was detected by
      clotting assays. aPS/PT, aCL and LA were more frequently found in patients with
      APS (47, 46 and 69, respectively) than in those without APS (11, 19 and 29,
      respectively) (OR 95% [CI]; 15.4 [7.2-32.7], 7.9 [4.1-15.2, 19.8 [9.6-40.6],
      respectively]. The sensitivity of each assay for the diagnosis of APS was 57%,
      56% and 86% with a specificity of 92%, 86% and 79%, respectively. aPS/PT and aCL
      have similar diagnostic value for APS, therefore, we propose that aPS/PT should
      be further explored, not only for research purposes, but also as a candidate of
      one of the laboratory criteria for the classification of the APS.

PMID- 15507289
TI  - Phenotyping the haemostatic system by thrombography--potential for the estimation
      of thrombotic risk.
AB  - The aim of this paper is to review the thrombogram and its use for phenotyping
      the haemostatic system. The thrombogram can be readily obtained through
      Calibrated Automated Thrombography (CAT), using a commercially available
      fluorometer, dedicated software (Thrombinoscope) and a calibrator. Here we
      explore the possibility to use platelet-rich plasma (PRP) triggered with a low
      amount of recombinant human tissue factor (approximately 0.5 pM) and also explore
      the function of the protein C system by adding activated protein C (APC) or
      soluble recombinant thrombomodulin (TM). Examples are shown: inherited
      antithrombin (AT) and protein C deficiencies, and antiphospholipid antibodies.

PMID- 15507290
TI  - Detection of procoagulant phospholipid interfering in tests for lupus
      anticoagulant.
AB  - Excess platelets shorten most clotting tests for lupus anticoagulant (LA). Often
      it is not clear if a shortened, normal or slightly prolonged result in a test
      masks a weak LA in combination with activated platelets, which express
      procoagulant phospholipid (PPL). Our aim was to investigate a new LA-insensitive
      factor Xa-activated clotting time (XACT) test for detecting PPL in plasma
      specimens submitted for LA testing. In most clotting tests for PPL, specimens are
      mixed with human platelet-free plasma (PFP) to correct for factor defects. Such
      tests are usually very sensitive to prolongation by LA, which act against PPL
      human clotting factor complexes. We found that phospholipid-free plasma from pigs
      could be used instead of human platelet-free plasma as substrate plasma without
      reducing sensitivity of XACT to PPL. However, the pig plasma-based system was
      significantly less affected by most LA. Activated platelets were detectable
      despite the presence of most LA. Since some LA still had significant prolonging
      effect on the XACT despite the use of pig plasma we investigated this further.
      ELISAs for IgG and IgM anti-beta2GP1 and anti-prothrombin antibodies were carried
      out on 23 specimens. We did not find that LA in plasmas displaying anti
      prothrombin antibodies had less prolonging effect on the test based on pig plasma
      than that using human platelet-free plasma. Similarly, there were no subtyping
      trends apparent among results from anti-beta2GPI-positive samples. Our results do
      not support the concept that anti-prothrombin-dependent LA might be more species
      specific than anti-beta2GPI-dependent LA.

PMID- 15507291
TI  - Minimal requirements for antiphospholipid antibodies ELISAs proposed by the
      European Forum on antiphospholipid antibodies.
AB  - Antiphospholipid ELISAs are part of the Antiphospholipid Antibodies Syndrome
      classification criteria, having the same diagnostic value as lupus anticoagulant.
      However, sometimes their results appear scarcely meaningful especially when wide
      metanalyses studies are performed, probably because of their well-known inter
      laboratory variability. The application of a common protocol was shown to improve
      the test reproducibility, but this observation did not have any influence on the
      routine performances. After discussion among experts at the European level, we
      identified four conditions named "minimal requirements" considered useful to
      decrease the inter-laboratory variability: (1) to run the samples in duplicate;
      (2) to determine the cut off level in each laboratory analysing at least 50
      samples from normal subjects, possibly age- and sex-matched with the patient
      population usually attending the Centre; (3) to calculate the cut-off level in
      percentiles; (4) to use stable external control in the tests. A collaborative
      study involving 36 European centres proved that the use of monoclonal anti-beta2
      glycoprotein I antibodies, HCAL (IgG) and EY2C9 (IgM) as standards, can help to
      reduce the inter-laboratory coefficient of variation both in anticardiolipin
      (aCL) and anti-beta2GPI (anti-beta2 glycoprotein I) ELISA. Therefore, we propose
      HCAL and EY2C9 as external controls, but other monoclonal or polyclonal
      preparations may be considered. During an interactive workshop held last May in
      Italy, 16 companies producing these tests agreed to consider the introduction of
      the "requirements" in their products. We suggest to adopt these "requirements"
      particularly in clinical studies, in order to compare more easily the literature
      data.

PMID- 15507292
TI  - Consensus guidelines for anticardiolipin antibody testing.
AB  - Despite the use of standardized GPL and MPL units, significant inter-laboratory
      and inter-method variation in anticardiolipin antibody (aCL) testing still
      exists, limiting the clinical utility and inter-laboratory portability of test
      results. This article reviews published and unpublished guidelines (some
      developed using consensus procedures) that can be used to improve various aspects
      of: (1) specimen collection; (2) aCL assay manufacture and testing procedures;
      (3) quality control; and (4) interpretation (including reporting) of results; and
      in doing so, improve the consistency of aCL results between different
      laboratories, assays and runs. However, there is a still a need for consensus
      guidelines that combine and deal with all of the aforementioned aspects of aCL
      testing and reporting.

PMID- 15507293
TI  - An adapted ELISA method for differentiating pathogenic from nonpathogenic aPL by
      a beta 2 glycoprotein I dependency anticardiolipin assay.
AB  - With the currently available commercial kits, as well as homemade assays for
      detecting anticardiolipin antibodies (aCL), it is not possible to discriminate
      nonpathogenic, beta 2 glycoprotein (GPI)-independent, infection-related
      antibodies from those of patients with the true autoimmune thrombotic syndrome,
      known as antiphospholipid syndrome (APS). We devised an assay that is able to
      differentiate these two types of antibodies by determining the beta 2 GPI
      requirements to bind in a cardiolipin ELISA. Beta 2 GPI was purified by
      perchloric acid precipitation, and fixed amounts were used in the dilution
      solutions of the tested samples that were also tested with no source of beta 2
      GPI. The ELISA plates were coated with cardiolipin, as usual, and blocked with a
      chicken ovalbumin solution. The serum samples had to be highly diluted in order
      not to have beta 2 GPI from the patient serum. The reaction was detected with
      alkaline phosphate tablets and developed with pNp in diethanolamine buffer. The
      adapted ELISA aCL assay described here was able to discriminate infectious
      [syphilis, hepatitis C virus (HCV), dengue fever, human immunodeficiency virus
      (HIV) and leprosy] and autoimmune [primary APS and systemic lupus erythematosus
      (SLE) related APS]. Further testing should be performed to demonstrate that this
      method consistently differentiates pathogenic antibodies that bind in an aCL
      ELISA only in the presence of beta 2 GPI.

PMID- 15507294
TI  - The appearance and disappearance of antiphospholipid autoantibodies subsequent to
      oxidation--reduction reactions.
AB  - The mechanisms that cause the appearance of autoantibodies are not understood.
      Compared to normal antibody production, factors responsible for autoantibody
      synthesis are more complex; they are thought to disrupt the normal mechanisms
      proposed to eliminate or down-regulate self-antibodies or to interfere with anti
      self-receptor editing. Data presented show that autoantibodies exist in the blood
      of all normal individuals. The autoantibodies appear after simple oxidation
      reduction (redox) reactions and react by ELISA, immunofluorescence, flow
      cytometry, Western blots, and in lupus anticoagulant (LA) assays.
      Antiphospholipid antibody (aPL) specificities detected after redox are
      cardiolipin (aCL), antiphosphatidylserine (aPS), antiphosphatidylethanolamine
      (aPE), antiphosphatidylcholine (aPC), and LA. These antibody activities were
      confirmed in several outside laboratories. The aPL isotypes detected in ELISA are
      plasma protein-dependent and include IgG, IgA, and IgM. Oxidizing agents tested
      to date include hemin, KMnO4, and NaIO4. Furthermore, aPL appear after exposure
      to direct current (DC)-mediated electromotive force. Alternating current (AC) is
      ineffective. Commercial IvIg preparations, also a source of IgG autoantibodies,
      provide a less complex milieu than plasma or serum for studying the biology of
      aPL redox-mediated mechanisms. Inhibition of hemin-mediated IvIg aPL conversion
      can be achieved by the addition of antioxidants, e.g., ascorbic acid, hemopexin,
      apotransferrin, and by addition of normal plasma or serum. Remarkably, the aPL
      specificities in the blood of autoimmunity patients disappear subsequent to
      application of redox reactions. These data document the hitherto unknown
      existence of redox-reactive autoantibodies in all normal individuals. The
      evolutionary persistence of these redox-sensitive antibodies raises interesting
      possibilities about their potentially beneficial role in immunological
      homeostasis.

PMID- 15507295
TI  - Libman-Sacks endocarditis associated with antiphospholipid syndrome and
      infection.
AB  - INTRODUCTION: Antiphospholipid syndrome (APS) is a systemic autoimmune disease,
      associated not only with a hypercoagulable state and recurrent fetal loss but
      with many diverse clinical manifestations including heart involvement,
      neurological manifestations, as well as skin, kidney and hematologic
      abnormalities. Cardiac manifestations include coronary by-pass graft and
      angioplasty occlusions, cardiomyopathy, cyanotic congenital heart disease,
      intracardiac thrombus and complications of cardiovascular surgery. The valvular
      heart disease was defined as Libman-Sacks nonbacterial endocarditis. Previously,
      we have shown a linear subendothelial deposition of anti-cardiolipin/beta2
      glycoprotein I (beta2GPI) antibodies in the valve specimens derived from APS
      patients. The involvement of complement C3c in the pathogenesis was documented.
      We assessed the beta2GPI-related target epitope recognized by the anti-beta2GPI
      Abs on the valves. MATERIALS AND METHODS: In order to find the beta2GPI-related
      target epitopes recognized by the anti-beta2GPI antibodies on the valves, we used
      beta2GPI-related synthetic peptides. The presence of anti-beta2GPI Abs on the
      studied valves was detected by anti-idiotypic antibody, followed by
      immunoperoxidase analysis. Biotin attached to the N-terminal of beta2GPI-related
      synthetic peptides and control peptide were used to identify the epitope
      addressed by the anti-beta2GPI Abs deposited on the patient's valve. The binding
      was probed by streptavidin-peroxidase and appropriate substrate. The specificity
      was confirmed by competition assays with control peptide and anti-idiotypic
      antibody. RESULTS: Among the beta2GPI-related synthetic peptides, two peptides
      were found in previous studies to mimic common pathogens either bacteriae or
      viruses, which raised a possible infectious origin for APS. One of these
      peptides, TLRVYK, is a specific target for anti-beta2GPI Abs deposited on the APS
      valves. This synthetic peptide was able to displace the anti-anti-beta2GPI anti
      idiotypic Abs for binding the anti-beta2GPI Abs on the valve by a competition
      assay. CONCLUSION: We point to the possibility that Libman-Sacks nonbacterial
      endocarditis may have an infectious origin.

PMID- 15507296
TI  - The lupus anticoagulant is a risk factor for myocardial infarction (but not
      atherosclerosis): Hopkins Lupus Cohort.
AB  - Antiphospholipid antibodies, both anticardiolipin and lupus anticoagulant, are
      common in SLE. We asked, in a prospective cohort, whether these antibodies are
      predictive of atherosclerosis and/or coronary artery disease. METHODS: Three
      hundred eighty patients, 92% female, 49% Caucasian, 51% African-American, mean
      age 46.4+/-12.3 years are followed quarterly, with assessment of both
      anticardiolipin and lupus anticoagulant (dRVVT). These patients underwent both
      helical CT and carotid duplex. RESULTS: Both the lupus anticoagulant and
      anticardiolipin are predictive of later venous or arterial thrombosis. Twenty
      years after diagnosis, SLE patients with the lupus anticoagulant (LA) have a 50%
      chance of a venous thrombotic event. Myocardial infarction occurs significantly
      more often in those with LA 22% vs. 9%, p=0.04. Neither anticardiolipin nor LA
      are associated with carotid IMT, carotid plaque, nor coronary calcium by helical
      CT. In aCL positive patients carotid IMT was 0.57+/-0.01 vs. 0.58+/-0.01 in aCL
      negative patients (p=NS); carotid plaque 0.47+/-0.13 vs. 0.32+/-0.10 (p=NS); and
      coronary calcium 65.4+/-37.4 vs. 65.4+/-30.2 (p=NS). In LA positive patients,
      carotid IMT was 0.59+/-0.03 vs. 0.59+/-0.02 in LA negative patients (p=NS);
      carotid plaque 0.07+/-0.02 (SE) vs. 0.80+/-0.02 (SE) (p=0.06); and coronary
      calcium 28.1+/-3.7 (SE) vs. 85.7+/-2.6 (SE) (p=NS). CONCLUSION: Antiphospholipid
      antibodies are not associated with subclinical atherosclerosis (carotid IMR,
      carotid plaque, helical CT coronary calcium), but are associated with actual
      thrombotic sequelae (myocardial infarction).

PMID- 15507297
TI  - Antiphospholipid antibodies and thrombosis: do test patterns identify the
      patients' risk?
AB  - We retrospectively analyzed the antiphospholipid profile of 103 lupus
      anticoagulant-positive patients to investigate whether laboratory patterns
      emerged for their association with arterial and venous thrombosis in the
      antiphospholipid syndrome. Anticardiolipin, anti-<beta>2-glycoprotein I and
      antiprothrombin antibodies were combined with coagulation tests in different
      patterns, which included from 2 to 5 laboratory variables. Overall, 22 out of 180
      available associations reached significance: 14 with any type of thrombosis and
      eight with venous thrombosis. In all but two cases, anticardiolipin antibodies>40
      units were present in the laboratory patterns that reached significance. Anti
      <beta>2-glycoprotein I antibodies were present in 11 significant patterns, and
      antiprothrombin antibodies in seven cases. Increasing the number of variables of
      the laboratory patterns did not increase the odds ratio (OR) towards thrombosis.
      In conclusion, this analysis confirmed that the presence of IgG anticardiolipin
      antibodies at medium to high titres, either alone or in various combinations with
      other tests, is clinically useful to establish the patients' risk of thrombosis.
      The role of the other antiphospholipid antibodies is less clear.

PMID- 15507299
TI  - The immune response to equine arteritis virus: potential lessons for other
      arteriviruses.
AB  - The members of the family Arteriviridae, genus Arterivirus, include equine
      arteritis virus (EAV), porcine reproductive and respiratory syndrome virus
      (PRRSV), lactate dehydrogenase-elevating virus (LDV) of mice, and simian
      hemorrhagic fever virus (SHFV). PRRSV is the newest member of the family (first
      isolated in North America and Europe in the early 1990s), whereas the other three
      viruses were recognized earlier (EAV in 1953, LDV in 1960, and SHFV in 1964).
      Although arterivirus infections are strictly species-specific, the causative
      agents share many biological and molecular properties, including their virion
      morphology, replication strategy, unique properties of their structural proteins,
      and their ability to establish distinctive persistent infections in their natural
      hosts. The arteriviruses are each antigenically distinct and cause different
      disease syndromes in their natural hosts. Similarly, the mechanism(s) responsible
      for the prolonged and/or persistent infections that characterize infections with
      each arterivirus in their natural hosts are remarkably different. The objective
      of this review is to compare and contrast the immune response to EAV with that to
      the other three arteriviruses, and emphasize the potential relevance of apparent
      similarities and differences in the neutralization characteristics of each virus.

PMID- 15507300
TI  - Apoptosis and porcine reproductive and respiratory syndrome virus.
AB  - Despite numerous studies examining the possible induction of apoptosis in porcine
      reproductive and respiratory syndrome virus (PRRSV)-infected cells, it remains
      unclear if PRRSV infection results in direct apoptotic induction. There is clear
      evidence that apoptotic cells are present in tissues from PRRSV-infected pigs.
      However, many of these studies have failed to show that the apoptotic cells are
      infected with PRRSV. This has led some investigators to propose that "bystander"
      cells, not infected cells, become apoptotic during PRRSV infection by a yet
      undetermined mechanism. Studies examining the induction of the apoptotic gene
      expression response to PRRSV infection are needed to determine if PRRSV
      replication triggers an apoptotic response. We have utilized microarray and semi
      quantitative reverse-transcription polymerase chain reaction (sqRT-PCR) to
      evaluate apoptotic gene expression in PRRSV-infected MARC-145 cells. Twenty-six
      apoptosis-related genes were examined during the first 24 h of infection and
      found to be unaltered, indicating that apoptotic induction was not occurring in
      PRRSV-infected cells. Additionally, using detection of free nucleosomal
      complexes, we examined cells for both apoptotic and necrotic death resulting from
      PRRSV infection at varying multiplicities of infection. This study indicates that
      PRRSV-infected MARC-145 cells undergo necrosis at a much higher level than
      apoptosis, and increases with virus levels used to infect the cells.

PMID- 15507301
TI  - Infectious cDNA clones of porcine reproductive and respiratory syndrome virus and
      their potential as vaccine vectors.
AB  - Full-length infectious cDNA clones have recently become available for both
      European and North American genotypes of porcine reproductive and respiratory
      syndrome virus (PRRSV), and it is now possible to alter the PRRSV genome and
      create genetically defined mutant viruses. Among many possible applications of
      the PRRSV infectious cDNA clones, development of genetically modified vaccines is
      of particular interest. Using infectious clones, the PRRSV genome has been
      manipulated by changing individual amino acids, deleting coding regions,
      inserting foreign sequences, and generating arterivirus chimeras. The limited
      available data suggest that all structural proteins of PRRSV are essential for
      replication of the virus, and that PRRSV infectivity is relatively intolerant of
      subtle changes within the structural proteins. The major tasks in PRRSV research
      are to identify virulence factors and pathogenic mechanisms, and to understand
      the structure-function relationships of individual viral proteins. Utilizing
      these infectious clones as tools, a new generation of safe and efficacious PRRS
      vaccines may be constructed.

PMID- 15507302
TI  - Role of neutralizing antibodies in PRRSV protective immunity.
AB  - Little has been known about the components of the immune system that are
      effective in the protection of a pig against PRRSV infection. Although antibodies
      were initially perceived as a deleterious, ineffective component of the PRRSV
      specific immune response, neutralizing antibodies (NA) are now considered to be
      an important correlate of protective immunity against PRRSV. This paper reviews
      the current knowledge on arterivirus-specific NA, the role that NA have in
      protection against infection with PRRSV, as well as the viral molecular
      structures that are responsible for the production of this type of antibodies by
      the pig. This information should prove central to the design of new generation
      vaccines against PRRSV.

PMID- 15507303
TI  - The combination of PRRS virus and bacterial endotoxin as a model for
      multifactorial respiratory disease in pigs.
AB  - This paper reviews in vivo studies on the interaction between porcine
      reproductive and respiratory syndrome virus (PRRSV) and LPS performed in the
      authors' laboratory. The main aim was to develop a reproducible model to study
      the pathogenesis of PRRSV-induced multifactorial respiratory disease. The central
      hypothesis was that respiratory disease results from an overproduction of
      proinflammatory cytokines in the lungs. In a first series of studies, PRRSV was
      shown to be a poor inducer of TNF-alpha and IFN-alpha in the lungs, whereas IL-1
      and the anti-inflammatory cytokine IL-10 were produced consistently during
      infection. We then set up a dual inoculation model in which pigs were inoculated
      intratracheally with PRRSV and 3-14 days later with LPS. PRRSV-infected pigs
      developed acute respiratory signs for 12-24h upon intratracheal LPS inoculation,
      in contrast to pigs inoculated with PRRSV or LPS only. Moreover, peak TNF-alpha,
      IL-1 and IL-6 titers were 10-100 times higher in PRRSV-LPS inoculated pigs than
      in the singly inoculated pigs and the cytokine overproduction was associated with
      disease. To further prove the role of proinflammatory cytokines, we studied the
      effect of pentoxifylline, a known inhibitor of TNF-alpha and IL-1, on PRRSV-LPS
      induced cytokine production and disease. The clinical effects of two non
      steroidal anti-inflammatory drugs (NSAIDs), meloxicam and flunixin meglumine,
      were also examined. Pentoxifylline, but not the NSAIDs, significantly reduced
      fever and respiratory signs from 2 to 6h after LPS. The levels of TNF-alpha and
      IL-1 in the lungs of pentoxifylline-treated pigs were moderately reduced, but
      were still 26 and 3.5-fold higher than in pigs inoculated with PRRSV or LPS only.
      This indicates that pathways other than inhibition of cytokine production
      contributed to the clinical improvement. Finally, we studied a mechanism by which
      PRRSV may sensitize the lungs for LPS. We hypothesized that PRRSV would increase
      the amount of LPS receptor complex in the lungs leading to LPS sensitisation.
      Both CD14 and LPS-binding protein, two components of this complex, increased
      significantly during infection and the amount of CD14 in particular was
      correlated with LPS sensitisation. The increase of CD14 was mainly due to
      infiltration of strongly CD14-positive monocytes in the lungs. The PRRSV-LPS
      combination proved to be a simple and reproducible experimental model for
      multifactorial respiratory disease in pigs. To what extent the interaction
      between PRRSV and LPS contributes to the development of complex respiratory
      disease is still a matter of debate.

PMID- 15507304
TI  - Effect of virus-specific antibodies on attachment, internalization and infection
      of porcine reproductive and respiratory syndrome virus in primary macrophages.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) induces respiratory
      distress in young pigs and reproductive failure in sows. In PRRSV infected pigs,
      virus persists for several weeks to several months. Although IPMA antibodies are
      detected from 7 days post inoculation (pi), virus neutralizing (VN) antibodies
      are commonly detected starting from 3 weeks pi with an SN test on Marc-145 cells.
      Since infection of Marc-145 cells is quite different compared to infection of
      macrophages, the in vivo target cell, the role of these VN antibodies in in vivo
      protection is questionable. In our study, we demonstrated that antibodies from
      pigs early in infection with PRRSV Lelystad virus (14 days pi) showed no
      neutralization in the SN test on Marc-145 cells, but partially reduced Lelystad
      virus infection of porcine alveolar macrophages. At 72 days pi, VN antibodies
      were detected by the SN test on Marc-145 cells, and these protected macrophages
      completely against Lelystad virus infection. In contrast, these VN antibodies
      only partially reduced porcine alveolar macrophage infection of a Belgian PRRSV
      isolate (homologous virus), and had no effect on infection of porcine alveolar
      macrophages with the American type VR-2332 strain (heterologous virus). Confocal
      analysis of Lelystad virus attachment and internalization in macrophages showed
      that antibodies blocked infection through both a reduction in virus attachment,
      and a reduction of PRRSV internalization. Western immunoblotting analysis
      revealed that sera from 14 days pi, which showed no neutralization in the SN test
      on Marc-145 cells but partially reduced Lelystad virus infection of macrophages,
      predominantly recognized the Lelystad virus N protein, and reacted faintly with
      the M envelope protein. Sera from 72 days pi, with VN antibodies that blocked
      infection of Marc-145 cells and PAM, reacted with the N protein and the two major
      envelope proteins M and GP5. Using the Belgian PRRSV isolate 94V360 an identical
      but less intense reactivity profile was obtained. VN sera also recognized the VR
      2332 N and M protein, but not the GP5 protein.

PMID- 15507305
TI  - Differential host cell gene expression regulated by the porcine reproductive and
      respiratory syndrome virus GP4 and GP5 glycoproteins.
AB  - The porcine reproductive and respiratory syndrome virus (PRRSV) GP4 and GP5
      proteins are two membrane-associated viral glycoproteins that have been shown to
      induce neutralizing antibodies. In the present study, the host cell gene
      expression profiles altered by the GP4 and GP5 proteins were investigated by the
      use of DNA microarrays. Sublines of Marc-145 and HeLa cells were established by
      stable transfection with open reading frame (ORF)4 and ORF5 of PRRSV,
      respectively, and differential gene expressions were studied using microarray
      chips embedded with 1718 human-expressed sequence tags. The genes for protein
      degradation, protein synthesis and transport, and various other biochemical
      pathways were identified. No genes involved in the apoptosis pathway appeared to
      be regulated in GP5-expressing cells. The microarray data may provide insights
      into the specific cellular responses to the GP4 and GP5 proteins during PRRSV
      infection.

PMID- 15507306
TI  - Deciphering the involvement of innate immune factors in the development of the
      host response to PRRSV vaccination.
AB  - The natural response of pigs to porcine reproductive and respiratory syndrome
      virus (PRRSV) infections and vaccinations needs to be altered so that better
      protection is afforded against both homologous and heterologous challenges by
      this pathogen. To address this problem, real-time gene expression assays were
      coupled with cytokine Elispot and protein analyses to assess the nature of the
      anti-PRRSV response of pigs immunized with modified live virus (MLV) vaccine.
      Although T helper 1 (Th1) immunity was elicited in all vaccinated animals, as
      evidenced by the genesis of PRRSV-specific interferon-gamma secreting cells (IFNG
      SC), the overall extent of the memory response was variable and generally weak.
      Peripheral blood mononuclear cells (PBMC) isolated from these pigs responded to
      PRRSV exposure with a limited increase in their expression of the Th1 immune
      markers, IFNG, tumor necrosis factor-alpha and interleukin-15 (IL15), and a
      reduction in the quantity of mRNAs encoding the innate and inflammatory proteins,
      IL1B, IL8 and IFNA. Efforts to enhance Th1 immunity, by utilizing an expression
      plasmid encoding porcine IFNA (pINA) as an adjuvant, resulted in a temporary
      increase in the frequency of PRRSV-specific IFNG SC but only minor changes
      overall in the expression of Th1 associated cytokine or innate immune marker mRNA
      by virus-stimulated PBMC. Administration of pINA, however, did correlate with
      decreased IL1B secretion by cultured, unstimulated PBMC but had no effect on
      their ability to release IFNG. Thus, while exogenous addition of IFNA during
      PRRSV vaccination has an impact on the development of a Th1 immune response,
      other alterations will be required for substantial boosting of virus-specific
      protection.

PMID- 15507307
TI  - Porcine reproductive and respiratory syndrome virus field isolates differ in in
      vitro interferon phenotypes.
AB  - Type I interferons (IFN-alpha and -beta) play an important role in the innate
      host defense against viral infection by inducing antiviral responses. In addition
      to direct antiviral activities, type I IFN serves as an important link between
      the innate and adaptive immune response through multiple mechanisms. Therefore,
      the outcome of a viral infection can be affected by IFN induction and the IFN
      sensitivity of a virus. North American porcine reproductive and respiratory
      syndrome virus (PRRSV) field isolates were studied with regard to IFN-alpha
      sensitivity and induction in order to understand the role of type I IFN in PRRSV
      pathogenesis. PRRSV isolates were differentially sensitive to porcine recombinant
      IFN-alpha (rIFN-alpha) and varied in their ability to induce IFN-alpha in porcine
      alveolar macrophages (PAM) cultures as measured by a porcine IFN-alpha specific
      ELISA on cell culture supernatants. Fifty-two plaques were purified from three
      PRRSV isolates (numbers 3, 7, and 12) and tested for IFN sensitivity and IFN
      induction. Plaque-derived populations were composed of heterogeneous populations
      in terms of IFN-inducing capacity and sensitivity to rIFN-alpha. When macrophages
      infected with isolates 3, 7, or 12 were treated with polycytidylic acid
      (polyI:C), IFN-alpha production was enhanced. Cells infected with isolate 3 and
      treated with polyI:C showed the most consistent and strongest enhancement of IFN
      alpha production. It was demonstrated that the relatively low concentrations of
      IFN-alpha produced by isolate 3 contributed to the enhanced IFN-alpha synthesis
      in response to polyI:C. Isolates 7 and 12 significantly suppressed the enhanced
      IFN-alpha production by isolate 3 in polyI:C treated cells. To determine if
      suppression was at the level of IFN-alpha transcription, quantitative RT-PCR was
      performed for IFN-alpha mRNA and compared to GAPDH and cyclophilin mRNA
      quantification. However, the relative number of IFN-alpha transcript copies did
      not correlate with IFN-alpha protein levels, suggesting a post-transcriptional
      mechanism of suppression. In summary, these results demonstrate that PRRSV field
      isolates differ both in IFN-alpha sensitivity and induction. Furthermore, a PRRSV
      field isolate strongly enhance polyI:C-induced IFN-alpha production in PAM
      cultures and this priming effect was suppressed by other PRRSV isolates.

PMID- 15507308
TI  - Pathogenic and humoral immune responses to porcine reproductive and respiratory
      syndrome virus (PRRSV) are related to viral load in acute infection.
AB  - Although much research has been performed on porcine reproductive and respiratory
      syndrome virus (PRRSV), little quantitative information is available on the
      relationships between virulence and in vivo virus replication, among isolates
      recovered at different times in the history of PRRS, or the relative levels of
      virulence associated with individual virus isolates. In this study, the in vivo
      growth properties of virulent field isolates and attenuated PRRSV isolates were
      compared. The results show that virulent PRRSV isolates exhibit longer and more
      elevated levels of viremia, induce faster and more intense humoral immune
      responses, negatively affect body weight gain, induce higher death rates, and
      cause more severe clinical signs in a respiratory disease model. We found that
      the more virulent field isolates grew to significantly higher levels in pigs than
      did cell-culture adapted isolates. We concluded that the pathogenic consequences
      and immunological responses of pigs to PRRSV are directly related to viral load
      in acute infection as reflected in viral titers in blood.

PMID- 15507309
TI  - Monoclonal antibody analysis of porcine reproductive and respiratory syndrome
      virus epitopes associated with antibody-dependent enhancement and neutralization
      of virus infection.
AB  - Enhanced infection and replication of porcine reproductive and respiratory
      syndrome (PRRS) virus in the presence of specific antibody has been demonstrated
      in vitro and in vivo, a phenomenon known as antibody-dependent enhancement (ADE).
      ADE is considered to be a significant obstacle to developing effective vaccines
      for many viruses for which ADE has been reported, since virus-specific antibodies
      of maternal origin or those conferred by vaccination can facilitate the entry of
      the virus into target cells, sometimes resulting in increased severity of the
      disease. In this study, the role of specific PRRS viral epitopes in ADE and/or
      virus neutralization (VN) was assessed in vitro using 14 monoclonal antibodies
      (mAbs) to 4 PRRS viral proteins: nucleocapsid (N), matrix (M), glycoprotein (GP)
      5, and GP3. Each mAb recognized a distinct epitope on one of these proteins. One
      way ADE and VN assays were performed in vitro using homologous PRRS virus
      isolates in the presence or absence of each mAb. ADE activity was determined by
      detecting a significant increase of progeny virus yield in porcine alveolar
      macrophage cultures in the presence of individual mAbs. Neutralizing activity was
      determined by detecting a significant reduction or complete blocking of virus
      replication in MARC-145 cells in the presence of individual mAbs. mAbs could be
      categorized into 3 groups: enhancing, neutralizing and neither. Viral epitopes
      which are capable of inducing neutralizing antibodies appeared to reside on the
      M, GP3 and GP5 proteins, while epitopes that may induce ADE-mediating antibody
      were associated with the N and GP5 proteins. Identification of the viral proteins
      and antigens and epitopes responsible for ADE- and VN-mediating antibodies may
      provide the basis for developing efficacious second-generation vaccines for the
      control of PRRS virus; yet, further epitope mapping remains to be done.

PMID- 15507310
TI  - The primary GP5 neutralization epitope of North American isolates of porcine
      reproductive and respiratory syndrome virus.
AB  - I have used indirect ELISA with overlapping synthetic peptides representing the
      GP5 ectodomain to study the generation and specificity of peptide-binding Abs in
      pigs that were infected in utero with porcine reproductive and respiratory
      syndrome virus (PRRSV) strain VR2332 and in North American field sera submitted
      for PRRSV infection diagnosis. Peptide-binding Abs appeared in sera of the VR2332
      infected pigs within about 30 days post-farrowing (dpf), reaching maximum titers
      100-200 dpf and then decreasing slowly to about half of maximum titer by about
      400 dpf. The formation of peptide-binding Abs and of virus neutralizing Abs
      correlated and their initial appearance coincided with disappearance of virus
      from the circulation. The Abs were specific for VR2332-specific peptides. In
      contrast, anti-N-protein Abs as measured by HerdCheck ELISA appeared within 7
      dpf, reached maximum levels at about 100 dpf and had decreased below detectable
      levels by about 200 dpf. Twenty-seven field serum samples with virus neutralizing
      activity all possessed high levels of peptide binding Abs, but the Abs bound
      about equally to VR2332 and strain Lelystad virus (LV)-specific peptides. The
      indirect ELISA results using various large peptides and competition ELISA using
      small peptides (8 or 9 amino acids long) confirmed that the epitope recognized by
      the Abs is located in the GP5 ectodomain sequence 37SHLQLIYNL of VR2332. Use of
      mutated peptides in the competition ELISA showed that 42I to T and 38HL to TY
      substitutions blocked Ab recognition, whereas deletion of 41L had no effect. In
      addition, 26 serum samples submitted by two farms for diagnostic tests were found
      to possess low levels of Abs that bound to GP5 ectodomain peptides, even though
      the sera were sero-negative in the HerdChek ELISA and lacked neutralizing
      activity. Competition ELISA showed that the Abs recognized one or more epitopes
      located downstream of the PRRSV neutralization epitope. An epitope(s) located in
      the same area was recognized by Abs generated in mice by immunization with a GP5
      ectodomain peptide conjugated to BSA. These Abs also lacked neutralizing
      activity.

PMID- 15507311
TI  - Construction and evaluation of genetically engineered replication-defective
      porcine reproductive and respiratory syndrome virus vaccine candidates.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) is an emerging
      pathogen causing significant economic losses in the swine industry worldwide. Two
      novel gene-deleted viruses were constructed and evaluated as vaccine candidates.
      Using the full-length infectious cDNA clone of North American PRRS isolate P129,
      the ORF2 and ORF4 genes (which encoded minor structural glycoproteins GP2a/2b and
      GP4, respectively) were individually deleted from the viral genome. Both deletion
      mutants were non-viable in MARC-145 cells and porcine alveolar macrophages,
      indicating that both genes are essential for virus replication. To rescue the
      replication-defective PRRSV, two complementing cell lines, MARC-2000 and MARC
      400, were established to stably express the PRRSV GP2 and GP4 proteins,
      respectively. These cells were able to complement the deleted gene function of
      PRRSV in trans and supported production of the replication-defective DeltaORF2
      PRRSV and DeltaORF4-PRRSV viruses. Both DeltaORF2-PRRSV and DeltaORF4-PRRSV
      viruses were propagated for 40-50 generations in the corresponding complementing
      cells and remained replication-defective in MARC-145 cells. To examine the
      immunogenic potential of the replication-defective PRRSV as vaccine candidates,
      four groups of pigs, 20 pigs per group, were immunized twice with DeltaORF2-PRRSV
      or DeltaORF4-PRRSV and challenged with the homologous virulent virus at 3 weeks
      post-immunization. In spite of the fact one group showed significant reduction in
      virus load, we could not demonstrate improvement from clinical diseases in this
      vaccination/challenge study. However, we did show that the cDNA clone of PRRSV
      can be a useful tool to genetically engineer PRRSV vaccine candidates and to
      study pathogenesis and viral gene functions.

PMID- 15507312
TI  - Immune responses of swine following DNA immunization with plasmids encoding
      porcine reproductive and respiratory syndrome virus ORFs 5 and 7, and porcine IL
      2 and IFNgamma.
AB  - In the present study, five eukaryotic double-gene expression plasmids containing
      porcine reproductive and respiratory syndrome virus (PRRSV) ORF5 and ORF7 genes
      combined with cDNAs encoding porcine IFNgamma and IL-2 were constructed for
      evaluation as PRRSV vaccine candidates. After immunization and viral challenge,
      two of three pigs immunized with pIRESorf5/IFNgamma, one of three pigs immunized
      with pIRESorf5/IL-2 and one of three pigs immunized with pIRESorf7/IL-2 were
      protected from lung lesions that were present in other vaccinated and control
      animals. Virus replication was reduced but not completely prevented in organs of
      the DNA-vaccinated animals as compared to controls. Therefore, the porcine
      cytokines IFNgamma and IL-2, delivered in combination with ORF5 or ORF7, may
      improve the immune efficacy of DNA vaccines against PRRSV.

PMID- 15507313
TI  - Cytokines and synthetic double-stranded RNA augment the T helper 1 immune
      response of swine to porcine reproductive and respiratory syndrome virus.
AB  - Immunization of pigs with a modified live porcine reproductive and respiratory
      syndrome virus (PRRSV) vaccine initially elicits a weak interferon (IFN)-gamma
      response. To improve the immune response, an adjuvant consisting of plasmid
      encoding either porcine interleukin (IL)-12 or IFN-alpha was co-administered
      during vaccination. In the presence of either adjuvant, at least a three-fold
      increase in the primary virus-specific IFN-gamma response was observed. While
      this enhancement was only transient (1 week) when the IL-12 expressing plasmid
      was used, the effect was not only still apparent at 6 weeks after vaccination in
      the presence of the IFN-alpha expressing plasmid but even after challenge with a
      virulent genetically divergent PRRSV. In contrast, no effect of either adjuvant
      on the production of anti-virus antibodies was noticed throughout the study.
      Despite the apparent augmentation of a T helper (Th) 1 type response by the
      inclusion of IFN-alpha or IL-12 during vaccination, this modulation did not
      necessarily correlate with a reduction in viremia. Since a similar increase in
      the degree of the IFN-gamma response to the PRRSV vaccine could be achieved by
      substituting polyinosinic-polycytidylic acid in lieu of either cytokine, exposure
      to PRRSV in the presence of a variety of Th 1 polarizing molecules can positively
      influence the development of the cell-mediated immune response of swine to this
      pathogen. Conceivably, such intervention could be applied to improve the
      formulation of anti-PRRSV vaccines.

PMID- 15507314
TI  - Beta-glucan enhancement of T cell IFNgamma response in swine.
AB  - Beta-glucan has been shown to enhance anti-tumor and anti-infection functions in
      animals. Pigs at 4 months of age were infected with porcine reproductive and
      respiratory syndrome virus (PRRSV), and peripheral blood monocytes (PBMC) were
      isolated for the detection of interferon gamma (IFNgamma)-producing cells. We
      found that soluble high molecular weight beta-glucan could increase IFNgamma
      producing cell frequency in a dose-dependent manner in the enzyme-linked
      immunospot assay (ELISPOT) in the absence of antigenic restimulation. A
      concentration as low as 1.6 microg/ml gave a significant increase and a similarly
      high enhancement was achieved at concentrations from 3.2 to 100 microg/ml. In
      PRRSV-specific IFNgamma ELISPOT, soluble beta-glucan elicited increased PRRSV
      specific responses at concentrations from 3.2 to 50 microg/ml, but not at 100
      microg/ml, whereas insoluble beta-glucan had no effect. Soluble beta-glucan
      augmented the porcine cellular immune response in an antigen-independent fashion,
      whereas insoluble beta-glucan had no activity. This finding suggests that soluble
      beta-glucan may enhance innate antiviral immunity against PRRSV.

PMID- 15507315
TI  - Humoral immune response induced by oral administration of S. typhimurium
      containing a DNA vaccine against porcine reproductive and respiratory syndrome
      virus.
AB  - The ORFs-encoded major envelope glycoprotein (GP5) of porcine reproductive and
      respiratory syndrome virus (PRRSV) is one of the major structural proteins of
      this virus. In this report, we described the induction of a PRRSV GP5-specific
      immune response by oral vaccination of mice with eukaryotic expression vectors
      containing the GP5 gene of PRRSV (pcDNA3-GP5), delived by attenuated Salmonella
      typhimurium aroA. It demonstrated that oral administration of the transformants
      resulted in expression of the GP5 transcript in the intestinal epithelium. The
      level of serum neutralization antibodies to PRRSV was not significantly different
      between the mice immunized with the transformants and the naked plasmid DNA. But
      the neutralizing antibody titres in sera of the mice immunized with SL7207/pcDNA3
      GP5' and pcDNA3-GP5' (resides 2-25 deletion mutant of GP5) were significantly
      lower than those immunized with the complete GP5 gene. These results show that
      oral inoculation of the transformants can induce humoral immune response to
      PRRSV. The signal peptide of the GP5 protein of PRRSV is associated with the
      neutralizing epitope of the protein. The attenuated S. typhimurium may be used as
      a delivery system for oral DNA vaccines containing PRRSV GP5 glycoprotein.

PMID- 15507316
TI  - Oral immunization induces local and distant mucosal immunity in swine.
AB  - Transmission of porcine reproductive and respiratory syndrome virus (PRRSV) in
      semen and reproductive disease in pregnant swine might be reduced by vaccines
      that induce mucosal immunity in the reproductive tract. Cholera toxin (CT), when
      delivered orally, is a potent mucosal adjuvant and immunogen in swine. To
      determine if oral immunization additionally elicits immunity at distant mucosal
      surfaces, we examined antibody responses to CT-B subunit in the reproductive
      tract and oral cavity. Orally administered CT induced distant mucosal immunity,
      as measured by antibodies to CT-B subunit in saliva and vaginal secretions.
      Presentation of PRRSV nucleocapsid as a genetic fusion with CT resulted in local
      mucosal antibody production, but no response was observed in vaginal secretions.
      The results demonstrate the feasibility of using orally administered CT for the
      induction of immunity to reproductive pathogens in swine. However, effective
      induction of PRRSV-specific immune responses in the reproductive tract requires a
      better understanding of the mechanisms of antigenicity and adjuvanticity at
      distant mucosal sites.

PMID- 15507317
TI  - Molecular characterization of a new leucine-rich repeat-containing G protein
      coupled receptor from a bivalve mollusc: evolutionary implications.
AB  - The family of leucine-rich repeat-containing G protein-coupled receptors (LGRs)
      shows members in both vertebrates and invertebrates including the most ancestral
      ones. Although this suggests an early evolutionary origin of this family of
      receptors, little is known about their diversity in molluscs, a major phylum of
      bilaterian invertebrates. Based on sequences of mammalian and insect LGRs, we
      have cloned and characterized a new typical LGR in the bivalve mollusc
      Crassostrea gigas. This receptor named Cg-LGRB exhibits high degree of amino acid
      sequence identity with both mammalian and Drosophila LGRs. Phylogenetic analysis
      indicates that Cg-LGRB belongs to the cluster of type B orphan LGRs and suggests
      that molluscs likely express the three LGR subgroups identified previously in
      other animals. Quantitative RT-PCR shows that Cg-LGRB is expressed mainly in the
      digestive gland and only at moderate levels in other organs and developmental
      stages. A possible involvement in the control of cytological changes occurring in
      bivalve mollusc digestive gland is discussed.

PMID- 15507318
TI  - The role of TFIID, the initiator element and a novel 5' TFIID binding site in the
      transcriptional control of the TATA-less human cytosolic phospholipase A2-alpha
      promoter.
AB  - Human cytosolic phospholipase A2-alpha (cPLA2-alpha) is a critical enzyme in the
      liberation of arachidonic acid (AA) from cellular membranes and the subsequent
      formation of prostaglandins (PGs), leukotrienes (LTs), hydroxyeicosatetraenoic
      acids (HETEs) and platelet activating factor in many different cell types. Much
      is known of the effect of posttranslational phosphorylation and calcium binding
      events on the enzymatic activity of cPLA2-alpha, but to date little is known
      about its specific transcriptional control. Through the use of reporter gene
      constructs and eletrophoretic mobility shift assays (EMSAs), this study
      determined the minimal promoter required for basal transcriptional activity of
      the human cPLA2-alpha promoter to include base pairs -40 through the
      transcription start site (TSS). In addition, it confirms the importance of an
      initiator (Inr) element at the TSS by deletion reporter gene analysis, and
      further identifies bases -3 (C) and -2 (T) as critical bases in the Inr function
      by mutation reporter gene analysis. Finally, this study describes a novel AAGGAG
      motif at -30 to -35 which is bound by TATA-box binding protein (TBP) and is
      critical for basal transcriptional activity.

PMID- 15507319
TI  - Transcriptional regulation of the AT1 receptor gene in immortalized human
      trophoblast cells.
AB  - Studies investigating the mechanisms that govern the expression of the human
      angiotensin II (Ang II) type 1 receptor (hAT1R) gene have progressed slowly due
      to the lack of human cell lines that express the AT1R. Recently, however, an
      immortalized human trophoblast cell line (HTR-8/SVNeo) was demonstrated to
      respond to Ang II. Therefore, we utilized this cell line to characterize the AT1R
      expressed on the cell surface and to investigate the mechanisms by which the
      hAT1R gene is regulated in these cells. HTR-8/SVNeo cells were shown to express
      functional high affinity AT1Rs having a Bmax value of 114+/-11 fmol/mg protein
      and a Kd value of 0.14+/-0.1 nM. Additionally, Ang II-induced IP3 production was
      mediated via the AT1R. Deletional analysis of the hAT1R promoter localized a
      major basal regulatory sequence within the -105 to -79 bp region, relative to the
      transcription start site, in HTR-8/SVNeo cells. Electrophoretic mobility shift
      assay (EMSA) and Chromatin Immunoprecipitation (ChIP) assay demonstrated that the
      transcription factors, Sp1 and Sp3, interact with this region of the hAT1R
      promoter in vitro and in vivo. Taken together, our data demonstrate that HTR
      8/SVNeo cells express functional AT1Rs and that basal level expression of this
      gene is regulated, in part, by Sp1 and Sp3 in this cell line.

PMID- 15507320
TI  - Isolation and characterization of Arabidopsis thaliana ISU1 gene.
AB  - We describe the isolation of a cDNA encoding Arabidopsis thaliana ISU1 (AtISU1),
      which regulates iron homeostasis in the mitochondria. The AtISU1 gene contained
      an open reading frame that encoded 167 amino acid residues. Northern blot
      analysis demonstrated that AtISU1 gene was ubiquitously expressed in plant
      tissues examined. The yeast seo5-1, which harbors a single base-pair deletion in
      ScISU1, is a suppressor of oxidative damage in sod1-deficient mutant. Based on
      comparative expression analyses using yeast ISU1 gene (ScISU1) in seo5-1 mutant,
      we found that AtISU1 acts as a counterpart of ScISU1.

PMID- 15507321
TI  - A point mutation in a silencer module reduces the promoter activity for the human
      mercaptopyruvate sulfurtransferase.
AB  - A promoter region of human mercaptopyruvate sulfurtransferase (MST) [EC 2.8.1.2]
      is G+C-rich and TATA-less, showing features of a house-keeping gene. In the core
      promoter, a GC box (-284:GGGGCGTGGC:-275) and an initiator (-219:TTATATG:-225)
      are found. A cap site hunting analysis for human liver cDNA revealed four
      possible transcriptional start sites, nucleotides -223, -159, -35 and -25. Point
      mutagenesis and deletion studies suggest that a module of the silencer element is
      -394:GCTG:-391. A replacement of -391G to C lost the silencer function; on the
      other hand, a replacement of -394G to T or C, -393C to T or -392T to G markedly
      reduced the promoter activity.

PMID- 15507322
TI  - Assessing African medicinal plants for efficacy and safety: agricultural and
      storage practices.
AB  - The paper reviews an important but little researched area of ethnopharmacology,
      namely, the effect of cultivation and post-harvest storage practices on levels of
      biological activity in traditionally used medicinal plants. Changes in COX-1
      inhibition and antibacterial activity, for example, occur at the onset of
      senescence and, in some species, are influenced by plant age. Plants in
      cultivation were also shown to have reduced anthelmintic and antibacterial
      activity while hypoxoside production was affected by nitrogen and phosphorous.
      Irrigation treatments, however, increased anthelmintic activity and, therefore,
      could be applied to medicinal plants cultivated in low rainfall areas. Pesticides
      have also been implicated in the regulation of plant growth and secondary
      metabolite production in cultivated medicinal plants, but residue levels have, so
      far, not been monitored. Post harvest storage of medicinal plants has been poorly
      researched in southern Africa. Available data indicates that antibacterial and
      anti-inflammatory activity changes following storage and is both species and
      temperature dependent. Similar trends were noted for materials that had been
      rapidly aged. Fatty acids with antibacterial activity are stable in dry specimens
      and, as such, may account for the fact that activity is unaffected by storage in
      certain instances.

PMID- 15507323
TI  - Cerbera odollam: a 'suicide tree' and cause of death in the state of Kerala,
      India.
AB  - Cerbera odollam is a tree belonging to the poisonous Apocynaceae family, which
      includes the yellow and common oleanders. The seeds are excessively toxic,
      containing cerberin as the main active cardenolide. Cerbera venenifera, a related
      species found in Madagascar, has a long history as an ordeal poison, and was
      responsible for the death of 3000 people per year in previous centuries. The
      odollam tree is responsible for about 50% of the plant poisoning cases and 10% of
      the total poisoning cases in Kerala, India. It is used both for suicide and
      homicide. The aim of this retrospective study is to call attention to a powerful
      toxic plant that is currently completely ignored by western physicians, chemists,
      analysts and even coroners and forensic toxicologists.

PMID- 15507324
TI  - Cytoprotective effect on oxidative stress and inhibitory effect on cellular aging
      of Uncaria sinensis Havil.
AB  - The ethanol extract from the hooks and stems of Uncaria sinensis Havil
      (Rubiaceae) exhibited significant inhibitory activity on oxidative stress and the
      age-dependent shortening of the telomeric DNA length. In the peroxidation model
      using t-BuOOH, the Uncaria sinensis extract showed a notable cytoprotective
      effect on the HEK-N/F cells with 65.0 +/- 3.0% of cell viability when compared
      with control cells at a concentration of 50 microg/ml. In addition, the Uncaria
      sinensis extract exhibited a significant cytoprotective effect against UVB
      induced oxidative damage. The life-span of the HEK-N/F cells was elongated by
      201% as a result of the continuous administration of 3 microg/ml of the Uncaria
      sinensis extract compared to that of the control. These observations were
      attributed to the inhibitory effect of the Uncaria sinensis extract on the age
      dependent shortening of the telomere length as shown by the Southern blots of the
      terminal restriction fragments (TRFs) of DNA extracted from subculture passages.

PMID- 15507325
TI  - Study on anti-diabetic activities of crude methanolic extracts of Loranthus
      micranthus (Linn.) sourced from five different host trees.
AB  - The hypoglycaemic and anti-hyperglycemic activities of dried leaves of Loranthus
      micranthus (Linn.) (Loranthaceae), parasitic on Persea americana, Baphia nitda,
      Kola acuminata, Pentaclethra macrophylla, Azadirchta indica, were evaluated in
      normoglycemic and alloxan-induced diabetic albino rats. Normoglycemic and alloxan
      induced diabetic rats were treated (intraperitoneally) with 200 mg/kg of the
      respective methanolic extracts of Loranthus micranthus (Linn.), glibenclamide
      (positive control), and 20% (v/v) Tween 20 solution (negative control). The sugar
      levels of the withdrawn blood samples were determined by o-toluidine
      spectrophotometric method. The studies indicate that the crude methanolic extract
      of Loranthus micranthus (Linn.) exhibited statistically significant hypoglycaemic
      (P < 0.001) and anti-hyperglycemic (P < 0.001) activities in normoglycemic and
      alloxan-induced diabetic albino rats, respectively. The hypoglycaemic effect was
      found to be dose-dependent. The maximum effect of the mistletoe extract (400
      mg/kg) from Persea americana on alloxan-induced diabetic rats was found to be
      statistically comparable with that of the positive control, glibenclamide, at 24
      h after administration, with a percentage reduction of blood sugar levels of
      82.59 and 83.34%, respectively. Acute toxicity tests of the methanolic extracts
      of Persea americana, Baphia nitda, Kola acuminata, Pentaclethra macrophylla,
      Azadirchta indica host trees in mice gave LD(50) values of 11650, 11650, 5900,
      5900 and 5900 mg/kg, respectively, which are all within the practically non-toxic
      range. The methanolic extract of African mistletoe was found to be a good
      candidate for alternative and/or complimentary medicine in the management of
      diabetes mellitus. The leaves of the Eastern Nigerian species of the African
      mistletoe harvested from Kola acuminata, Azadirchta indica and Baphia nitda host
      trees exhibited comparatively better anti-hyperglycemic activities among the host
      trees studied.

PMID- 15507326
TI  - Effects of Anacardium occidentale stem bark extract on in vivo inflammatory
      models.
AB  - The methanol extract of Anacardium occidentale stem bark was evaluated for
      activities against the lipopolysaccharide (LPS)-induced septic shock, as well as
      LPS-induced microvascular permeability in mice. Pre-treatment with Anacardium
      occidentale extract (25-200 mg/kg) caused a dose-dependent and significant (p <
      0.05) reduction in the elevated levels of alanine and aspartate aminotransferases
      in the sera of D-galactosamine-primed mice injected with LPS. The highest dose of
      the extract studied (200 mg/kg) produced a 100% protection against death from
      sepsis. Pentoxifylline (100 mg/kg) and L-NAME (5 mg/kg) offered 100% protection
      against LPS-induced septic shock, and produced marked reduction in elevated
      levels of transferases. A dose-related inhibition of LPS-induced microvascular
      permability in mice was also produced by pentoxifylline, L-NAME and the extract.

PMID- 15507327
TI  - Hepatoprotective and anti-inflammatory activities of Ballota glandulosissima.
AB  - Water extract of Ballota glandulosissima Hub.-Mor & Patzak (Lamiaceae) (BG) was
      investigated for anti-inflammatory activity using the carrageenan-induced rat paw
      oedema test and for hepatoprotective effect on carbon tetrachloride (CCl(4))
      induced hepatotoxicity in rats. Biochemical parameters of hepatic damage such as
      serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline
      phosphatase (ALP) and bilirubin concentrations were determined. CCl(4) (0.8 mL/kg
      i.p. for 7 days) treatment increased the serum AST, ALT, ALP and bilirubin levels
      significantly as compared to controls. Treatment of animals with BG (100 mg/kg,
      i.p.) +CCl(4) (0.8 mL/kg i.p.) for 7 days significantly ameliorated the levels of
      AST, ALT and ALP elevated by the CCl(4) treatment alone. The results of
      biochemical tests were also confirmed by histopathological examination. BG
      together with CCl(4) treatment decreased the balloning degeneration but did not
      produced apoptosis of hepatocytes, centrilobular and bridging necrosis observed
      in the CCl(4) treatment alone. BG, at 100 mg/kg per os, showed a significant
      reduction (34.22%) in rat paw oedema induced by carrageenan. The reference anti
      inflammatory drugs etodolac (50 mg/kg, p.o.) and indomethacin (3 mg/kg, i.p.)
      significantly reduced the oedeme by 43.42 and 95.70%, respectively. The present
      study reveals that the water extract of Ballota glandulosissima possesses
      promising protective activity against CCl(4) induced hepatic damage and anti
      inflammatory activity in rats.

PMID- 15507328
TI  - Chemical composition and antimicrobial activity of the essential oils of Anthemis
      xylopoda O. Schwarz from Turkey.
AB  - The chemical composition and the antimicrobial activity of the essential oils
      isolated from the leaves (LEO) and flowers (FEO) of Anthemis xylopoda, an endemic
      taxon of Turkey, were investigated. Borneol was the major constituent of both the
      oils studied (30.15 and 31.85%, respectively). The antimicrobial activities of
      both oils were separately evaluated against 13 microorganisms. The disc diffusion
      method was used for the antimicrobial activity test. Results showed that both
      oils of Anthemis xylopoda exhibited a significant antimicrobial activity.

PMID- 15507329
TI  - Free radical scavengers and antioxidants from Baccharis grisebachii.
AB  - The exudate and seriated extracts from the aerial parts of Baccharis grisebachii
      (Asteraceae) which is recommended as a digestive and to relieve gastric ulcers in
      Argentina, showed activity as free radical scavengers and inhibited
      lipoperoxidation in erythrocytes. Assay-guided isolation led to seven p-coumaric
      acid derivatives and six flavonoids as the main active constituents of the crude
      drug. The activity towards the superoxide anion was mainly due to the flavonoid
      constituents. 5,7,4'-Trihydroxy-6-methoxyflavone and quercetin presented high
      activity (64 and 79%) even at 12.5 microg/ml. The xanthine oxidase inhibitory
      effect of the extracts can be related with the p-coumaric acid derivatives
      drupanin, 4-acetyl-3,5-diprenylcinnamic acid and trans-ferulic acid O-hexan-3
      onyl-ether which showed IC(50) values in the range 28-40 microg/ml. Both p
      coumaric acid derivatives and flavonoids inhibited lipoperoxidation in
      erythrocytes. The highest activity was found for the p-coumaric acid derivatives
      4-acetyl-3-prenyl-ethoxycinnamate, 3-prenyl-4-(4'-hydroxydihydrocinnamoyloxy)
      cinnamate and trans-ferulic acid O-hexan-3-onyl-ether (69-82%) and the flavonoids
      5,7,4'-trihydroxy-6-methoxyflavone, quercetin, 5,7,4'-trihydroxy-6,3'
      dimethoxyflavone and 5,7,4'-trihydroxy-6,8-dimethoxyflavone (64-84%) at 100
      microg/ml. The most active free radical scavengers measured by the DPPH
      decoloration assay were the p-coumaric acid derivatives drupanin and trans
      ferulic acid O-hexan-3-onyl-ether (27-35% at 10 microg/ml) and the flavonoid
      quercetin (97 and 23% at 10 and 1 microg/ml, respectively). The results support
      the use of Baccharis grisebachii in Argentinian traditional medicine.

PMID- 15507330
TI  - Endothelium-dependent vasorelaxing activity of aqueous extracts of lyophilized
      seeds of Casimiroa edulis (AECe) on rat mesenteric arterial bed.
AB  - The vasorelaxing activity of the aqueous extracts of Casimiroa edulis seeds
      F(AECe) on mesenteric arterial bed (MAB) of rats was studied. MAB precontracted
      with methoxamine was mounted on a tissue bath and exposed to plant extracts
      (bolus 50, 500, 2500 and 5000 microg). The bolus injections of AECe significantly
      inhibited, in a concentration-dependent manner, the maximal contractile response
      induced by methoxamine (30 microm) in MAB. After endothelium removal, the
      vascular ability of Casimiroa edulis aqueous extract was significantly changed.
      Treatment with an inhibitor of NO synthase (L-NOA, 10 microM) also modified the
      AECe effect. The guanilate cyclase inhibitor methylene blue (MB, 100 microM)
      inhibited the AECe-induced vasodilatation. These results suggest the involvement
      of NO of endothelial source (or related factors) in this vasodilator effect.

PMID- 15507331
TI  - Pharmacological basis for the gut stimulatory activity of Raphanus sativus
      leaves.
AB  - The crude extract of Raphanus sativus leaves (Rl.Cr) showed a dose-dependent
      (0.03-5.0 mg/ml) spasmogenicity in guinea-pig ileum and colon. The effect was
      insensitive to atropine pre-treatment but was completely abolished by pyrilamine
      indicating involvement of histaminergic (H(1)) receptors. The contractile effect
      at high doses (3.0-5.0mg/ml) was followed by relaxation. Rl.Cr also enhanced the
      transit of charcoal meal in mice at 30-100 mg/kg. The petroleum spirit,
      chloroform and aqueous fractions all showed histaminergic activity in ileum;
      aqueous fraction being more potent. The study shows the presence of a
      histaminergic component(s) along with a weak spasmolytic factor thus providing
      sound mechanistic basis for the traditional use of the plant in constipation.

PMID- 15507332
TI  - The efficacy of Sphaeranthus senegalensis Vaill extract against diarrhoea in
      rats.
AB  - The aqueous extract of Sphaeranthus senegalensis (Asteraceae) was investigated
      for anti-diarrhoeal activity in rats. Its effect on castor oil-induced diarrhoea
      and fluid accumulation and on gastrointestinal (charcoal meal) test was
      evaluated. Results showed that pre-treatment for 30 min with the extract at 50,
      100 and 200 mg/kg, p.o. causes a dose-dependent protection against castor oil
      induced diarrhoea and intraluminal fluid accumulation and inhibited
      gastrointestinal transit motility. These results suggest that the plant contain
      active constituents that may be useful against diarrhoea.

PMID- 15507333
TI  - Anti-inflammatory and hypoglycaemic effects of Tetrapleura tetraptera (Taub)
      [Fabaceae] fruit aqueous extract in rats.
AB  - The fruit of Tetrapleura tetraptera (Taub) [Fabaceae] is frequently used in
      Tropical African traditional medicine for the management and/or control of an
      array of human ailments, including arthritis and other inflammatory conditions,
      asthma, diabetes mellitus, hypertension, epilepsy, schistosomiasis, and so on.
      The present study was undertaken to examine the anti-inflammatory and
      hypoglycaemic effects of Tetrapleura tetraptera (Taub) fruit aqueous extract in
      rats. Fresh egg albumin-induced pedal oedema and streptozotocin (STZ)-induced
      diabetes mellitus were used as experimental test models of inflammation and
      diabetes. Diclofenac (DIC, 100mg/kg p.o.) and chlorpropamide (250 mg/kg p.o.)
      were employed as reference anti-inflammatory and hypoglycaemic agents,
      respectively, for comparison. Tetrapleura tetraptera (TTE, 50-800 mg/kg p.o.)
      produced dose-related, significant reductions (P < 0.05-0.001) of the fresh egg
      albumin-induced acute inflammation of the rat hind paw oedema. The plant extract
      (TTE, 50-800 mg/kg p.o.) also produced dose-dependent, significant reductions (P
      < 0.05-0.001) in the blood glucose concentrations of both fasted normal and
      fasted diabetic rats. The results of this experimental animal study indicate that
      T. tetraptera fruit aqueous extract possesses anti-inflammatory and hypoglycaemic
      properties. These findings lend pharmacological credence to the suggested
      folkloric uses of the plant's fruit in the management and/or control of arthritis
      and other inflammatory conditions, as well as in adult-onset, type-2 diabetes
      mellitus in some Yoruba-speaking communities of South-Western Nigeria.

PMID- 15507334
TI  - Thai medicinal plants modulate nitric oxide and tumor necrosis factor-alpha in
      J774.2 mouse macrophages.
AB  - Centella asiatica (CA) and Rhinacanthus nasutus (RN) are Thai medicinal plants
      traditionally used to treat a variety of disorders including inflammatory
      conditions and infections. Nitric oxide (NO) produced from activated macrophages
      plays a role in both inflammatory and anti-inflammatory processes. This study
      examined whether CA and RN modulate the production of NO and tumour necrosis
      factor-alpha (TNF-alpha) by J774.2 mouse macrophages. Expression of the inducible
      nitric oxide synthase (iNOS) and TNF-alpha genes was also analysed. With CA
      (water extract) NO production was increased in a dose-dependent manner. An
      increase also occurred when CA was administered with lipopolysaccharide (LPS), a
      known macrophage activator. In contrast, an ethanol extract of CA had no effect
      on NO, and when administered with LPS the extract suppressed production. With RN,
      neither water nor ethanol extracts alone had an effect on NO, although when the
      ethanol extract of RN was used in combination with LPS, production was increased.
      TNF-alpha secretion was correlated with NO production and increases were
      associated with an elevation in TNF-alpha mRNA. The only effect on iNOS gene
      expression was an inhibition with the CA ethanol extract in the presence of LPS,
      consistent with the reduction in NO under these conditions. These studies show
      that CA and RN extracts can either increase or decrease NO production by
      macrophages and that these effects are predominantly mediated through an effect
      on TNF-alpha expression. These data contribute to a better mechanistic
      understanding of the medicinal properties of these Thai plants.

PMID- 15507335
TI  - Cissampelos sympodialis Eichl. (Menispermaceae): oral treatment decreases IgE
      levels and induces a Th1-skewed cytokine production in ovalbumin-sensitized mice.
AB  - The murine model of ovalbumin (OVA)-induced allergy was used to evaluate the
      effectiveness of oral treatment with the leaf extract of Cissampelos sympodialis
      Eichl. (Menispermaceae) (CS) in the modulation of immunoglobulin E (IgE)
      production and T cell activation. CS treatment with doses ranging from 200 to 600
      mg/Kg/day for 15 days before and during OVA-sensitization promoted reduction in
      total and OVA-specific serum IgE. CS at 400 or 600 mg/Kg/day also reduced paw
      edema induced by local OVA challenge. Daily intake of up to 600 mg/Kg of oral CS
      by BALB/c mice did not reduce weight gain, which is indicative of a lack of
      systemic toxicity. To assess the effect of CS treatment on T cell proliferative
      response to stimuli in vitro, the mitogenic response of spleen cells of treated
      and control animals were evaluated. Cells from CS-treated animals showed an
      elevated background proliferative response to concanavalin-A (Con-A) when
      compared to those from control animals. Oral intake of CS increased the in vitro
      production of IFN-gamma and IL-10 by Con-A stimulated cells. Mice treated with
      200 mg/Kg/day CS showed increasing levels of IFN-gamma. These results show that
      oral treatment with Cissampelos sympodialis extract has an immunomodulatory
      effect, reducing allergy-associated responses possibly by a preferential
      activation of Th1-type cytokines.

PMID- 15507336
TI  - Memory retrieval improvement by Ptychopetalum olacoides in young and aging mice.
AB  - Amazonian peoples use traditional remedies prepared with Ptychopetalum olacoides
      (PO) roots for treating various age-related conditions. This study shows that a
      single intraperitoneally (i.p.) administration of Ptychopetalum olacoides ethanol
      extract (POEE, 50 and 100mg/kg) improved memory retrieval in step-down inhibitory
      avoidance (P <or= 0.05 and P <or= 0.01, test session latency 102 [19.38-300] and
      192 [91.3-300]s, respectively versus control 24.7 [12.9-89.6]), without
      interfering with acquisition or consolidation in adult (2.5-month-old) mice.
      Comparable results were obtained with POEE given p.o. at 800 and 1000mg/kg (P
      <or= 0.05 and P <or= 0.01, 52.7 [19.5-297.2] and 85.7 [44.4-260.4] versus control
      20.5 [8-92.6]). Moreover, memory amelioration was also observed (P <or= 0.01) in
      aging (14 months) mice presenting memory deficit (14.95 [10.8-41]) as compared to
      adult (2.5 months) mice (57 [15.7-141.2]), with the extract given acutely i.p.
      100 mg/kg (300 [133.1-300] versus control 14.95 [10.8-41]) or p.o. 800 mg/kg
      (28.4 [15.1-84.6] versus control 11.5 [7.8-23.3]). Indeed, aging mice treated
      with POEE (800 mg/kg, p.o.) performed as well as adult mice. Consistently with
      its traditional use, the data suggest that POEE facilitates memory retrieval.
      Although the antioxidant and acetylcholinesterase inhibitory properties
      previously described for this extract may be of relevance, the molecular
      mechanism(s) underlying the improvement in memory retrieval here reported merit
      further scrutiny.

PMID- 15507337
TI  - Screening for antihyperglycaemic activity in several local herbs of Malaysia.
AB  - Screening of aqueous extract of Phyllantus niruri (PL), Zingiber zerumbet (ZG),
      Eurycoma longifolia (TA-a and TA-b) and Andrographis paniculata (AP) to determine
      their blood glucose lowering effect were conducted in normoglycaemic and
      Streptozotocin-induced hyperglycaemic rats. Significant reduction in blood
      glucose level at 52.90% was shown when hyperglycaemic rats were treated with 50
      mg/kg body weight (BW) aqueous extract of AP. This effect is enhanced when freeze
      dried material was used, where 6.25 mg/kg BW gave 61.81% reduction in blood
      glucose level. In the administration of TA-a and TA-b, positive results in
      hyperglyacaemic rats were only obtained when 150 mg/kg BW of the aqueous extract
      was used. No significant reduction in blood glucose level were shown in
      hyperglycaemic rats treated with PL and ZG at all concentrations used (50, 100
      and 150 mg/kg BW). In normoglycaemic rats, no significant reduction was noted
      when all the same extracts were used.

PMID- 15507338
TI  - A cyclooxygenase (COX) inhibitory biflavonoid from the seeds of Semecarpus
      anacardium.
AB  - Semecarpus anacardium Linn., Anacardiaceae, is being most commonly used in India
      for the treatment of rheumatoid arthritis and other inflammatory disorders.
      Bioactivity guided fractionation of ethyl acetate extract led to the isolation of
      major active principle, tetrahydroamentoflavone (THA), a biflavonoid. The in
      vitro cyclooxygenase (COX-1) catalyzed prostaglandin biosynthesis assay of THA
      gave an IC(50) value of 29.5 microM (COX-1) and 40.5% inhibition at 100 microg/mL
      (COX-2). The in vivo carrageenan induced paw edema assay resulted in dose
      dependent anti-inflammatory effect of THA and the activity was comparable to that
      of ibuprofen, one of the well known NSAIDs.

PMID- 15507339
TI  - Isolation of anti-ulcerogenic sesquiterpene lactones from Centaurea solstitialis
      L. ssp. solstitialis through bioassay-guided fractionation procedures in rats.
AB  - The fresh spiny flowers of Centaurea solstitialis ssp. solstitialis (CSS) are
      used for the treatment of peptic ulcers in Turkey. Ethanol (80%) extract of CSS
      exhibited significant anti-ulcerogenic effect on the ethanol-induced
      ulcerogenesis model in rats. The ethanol extract was further fractionated by
      successive solvent extractions with n-hexane, chloroform, ethyl acetate and n
      butanol. All fractions showed significant anti-ulcerogenic activity, however, the
      effect of the chloroform fraction was found to be more prominent with 99.5% ulcer
      inhibition. Bioassay-guided fractionation yielded sesquiterpene lactones as the
      active components. The main components responsible for the activity of the
      chloroform fraction were determined as chlorojanerin and 13-acetyl solstitialin A
      which were elucidated by HR-ESI and (1)H, (13)C and 2D NMR spectroscopic
      techniques.

PMID- 15507340
TI  - The ambrosanolide cumanin inhibits macrophage nitric oxide synthesis: some
      structural considerations.
AB  - Since its role in inflammatory diseases was recognized, nitric oxide (NO) has
      become an important mediator to evaluate anti-inflammatory agents. Sesquiterpene
      lactones, which occur in several medicinal plants, inhibit the NO production in
      macrophage-like cells. This action is probably due to a 1,4 addition reaction
      between its alpha,beta-unsaturated carbonyl group with sulfhydryl (SH)-containing
      compounds. For this reason it is believed that these compounds are cytotoxic,
      which restricts their therapeutic use. In this contribution, the ability of the
      ambrosanolide-type sesquiterpene lactone cumanin (from the Asteraceae Ambrosia
      psilostachya) to inhibit NO biosynthesis was evaluated in lipopolisaccharide
      induced peritoneal murine macrophages and its cytotoxicity was assessed in the
      MTT assay. Cumanin showed a potent inhibitory effect in NO production (IC(50) =
      9.38+/-0.38 microM) with low cytotoxicity. The 1,4-addition reaction of thiols
      was slow, which does not explain the inhibition of NO production but does explain
      the low cytotoxicity of cumanin with respect to other lactones.

PMID- 15507341
TI  - Evaluation of the antioedematogenic, free radical scavenging and antimicrobial
      activities of aerial parts of Tillandsiastreptocarpa Baker-Bromeliaceae.
AB  - The crude methanolic extract of the aerial parts of Tillandsiastreptocarpa was
      investigated for their acute toxicity and antioedematogenic, antioxidant and
      antimicrobial activities. Also, the antioedematogenic activity of the hexane
      fraction resulting from the partition of the crude methanolic extract was
      evaluated. The methanolic extract and the hexane fraction showed significant (P <
      0.05) inhibition of ear oedema, observed at 2 mg/ear in the croton oil-induced
      mice ear oedema test. In the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical
      scavenging test, a high reactivity and potent antioxidant effect (IC(50) =
      0.0056%, w/v) were observed for the methanolic extract. The antimicrobial
      activity assay showed that the crude methanolic extract was inactive toward
      Escherichiacoli, Staphylococcusaureus, Pseudomonasaeruginosa, Bacillussubtilis,
      Candidaalbicans, C. parapsilosis, C. krusei and C. tropicalis (MIC > 500
      microg/ml). The methanolic extract showed no toxic effect on mice at a single
      dose of 2000 mg/kg (p.o). Common side effects including mild diarrhoea, loss of
      weight and depression were not recorded. The compounds cycloartenol, 4',5
      dihydroxy-3',7-dimethoxyflavanone and a mixture of the steroids stigmasterol,
      beta-sitosterol and campesterol, were isolated from the hexane fraction and
      identified by spectroscopic methods.

PMID- 15507342
TI  - The antinociceptive effect of some Egyptian medicinal plant extracts.
AB  - The antinociceptive effect of methanolic extracts (200 and 400 mg kg(-1)) of
      eight Egyptian medicinal plants was studied using acetic acid-induced writhing
      and tail-flick test in mice. Oral administration of 400 mg kg(-1) methanolic
      extracts of Convolvulus fatmensis, Alhagi maurorum, Plantago major seeds, Conyza
      dioscaridis significantly (P < 0.05) inhibited the nociception to acetic acid
      induced writhes with a protection of 85.5-61.3%. Schouwia thebaica, Diplotaxis
      acris, Plantago major leaves and Mentha microphylla, in the large dose, showed a
      protection of 50.8-45.8%, which were significantly different as compared to
      control. The smaller dose of the tested plant extracts did not protect animals
      from painful acetic acid stimulation with the exception of Alhagi maurorum. In
      the tail-flick test, methanolic extracts of Mentha microphylla, Conyza
      dioscaridis, Alhagi maurorum, Plantago major leaves, Diplotaxis acris and
      Convolvulus fatmensis in a dose of 400 mg kg(-1) produced significant increase in
      the latency to response of tail to thermal stimulation. Mild or no effect was
      observed by the small dose with the exception of Diplotaxis acris that had
      significant antinociceptive effect at the dose of 200 mg kg(-1). The extracts of
      all tested plants in doses up to 2 g kg(-1) b.wt. did not cause any deaths or
      major signs of acute toxicity. Phytochemical screening indicated the presence of
      unsaturated sterols, triterpenes, tannins, flavonoids and carbohydrates and/or
      glycosides as major constituents.

PMID- 15507343
TI  - In vitro pharmacological investigations of Sapindus trifoliatus in various
      migraine targets.
AB  - Phytotherapies have offered alternative sources of therapy for migraine and
      gained much importance in prophylactic treatment. The aqueous extract of pericarp
      of fruits of Sapindus trifoliatus Linn (ST), family Sapindaceae was evaluated for
      its affinity for 5-HT(1B/1D) receptors in rabbit saphenous vein, alpha
      adrenoceptors in rabbit aorta, GABA receptors in guinea pig ileum, 5-HT(2B)
      receptors in rat fundus and vanilloid receptors in guinea pig trachea. The
      calcium blocking effect was studied in rabbit aorta while the modulatory role of
      ST on platelet serotonin release was evaluated in human platelets. The aqueous
      extract of Sapindus trifoliatus exhibited significant 5-HT(2B) receptor
      inhibition and moderate platelet serotonin release inhibition.

PMID- 15507345
TI  - In vitro biological activity and essential oil composition of four indigenous
      South African Helichrysum species.
AB  - Helichrysum species are used widely to treat various medical conditions. In this
      study, the anti-microbial, anti-oxidant (DPPH assay) and anti-inflammatory
      activity (5-lipoxygenase assay) of Helichrysum dasyanthum, Helichrysum felinum,
      Helichrysum excisum and Helichrysum petiolare were investigated. The essential
      oil compositions of these species were determined. The acetone and methanol
      extracts as well as the essential oils exhibited activity against Gram-positive
      bacteria, while both the methanol and acetone extracts of all four species were
      active in the anti-oxidant assay. The essential oils, on the other hand,
      displayed activity in the 5-lipoxygenase assay, which was used as an indication
      of anti-inflammatory activity. Two extracts exhibited promising activity in the
      anti-microbial assay, the acetone extract of Helichrysum dasyanthum with a MIC
      value of 15.63 microg/ml and the methanol extract of Helichrysum excisum with a
      MIC value of 62.5 microg/ml. The acetone extract of Helichrysum dasyanthum was
      the most active free radical scavenger in the DPPH assay (IC(50) of 9.53
      microg/ml) while values for the anti-inflammatory activity of the essential oils
      ranged between 25 and 32 microg/ml. The essential oil compositions of three
      species (Helichrysum dasyanthum, Helichrysum excisum and Helichrysum petiolare)
      were dominated by the presence of monoterpenes such as alpha-pinene, 1,8-cineole
      and p-cymene. In the oil of Helichrysum felinum, monoterpenes were largely
      absent. Its profile consisted of a variety of sesquiterpenes in low
      concentrations with beta-caryophyllene dominating.

PMID- 15507344
TI  - Anti-malarial activity of some xanthones isolated from the roots of Andrographis
      paniculata.
AB  - Four xanthones were isolated from the roots of Andrographis paniculata using a
      combination of column and thin-layer chromatographic methods. They were
      characterized as (i) 1,8-di-hydroxy-3,7-dimethoxy-xanthone, (ii) 4,8-dihydroxy
      2,7-dimethoxy-xanthone, (iii) 1,2-dihydroxy-6,8-dimethoxy-xanthone and (iv) 3,7,8
      trimethoxy-1-hydroxy xanthone by IR, MS and NMR spectroscopic methods. In vitro
      study revealed that compound 1,2-dihydroxy-6,8-dimethoxy-xanthone possessed
      substantial anti-plasmodial activity against Plasmodium falciparum with its
      IC(50) value of 4 microg ml(-1). Xanthones bearing hydroxyl group at 2 position
      demonstrated most potent activity while xanthones with hydroxyl group at 1,4 or 8
      position possessed very low activity. In vivo anti-malarial sensitivity test of
      this compound on Swiss Albino mice with Plasmodium berghei infection using
      Peters' 4-day test gave substantial reduction (62%) in parasitaemia after
      treating the mice with 30 mg kg(-1) dose. In vitro cytotoxicity against mammalian
      cells revealed that 1,2-dihydroxy-6,8-dimethoxy-xanthone is non-cytotoxic with
      its IC(50) > 32 microg ml(-1).

PMID- 15507346
TI  - Anti-inflammatory and anti-nociceptive activity of the water decoction Desmodium
      gangeticum.
AB  - The water decoction of root and aerial parts of Desmodium gangeticum
      (Leguminosae) was examined for anti-inflammatory and anti-nociceptive activity in
      experimental animals. The root and aerial decoction in doses of 5, 10 and 20 mg
      /kg caused a dose-dependent inhibition of swelling caused by carrageenin
      equivalent to 14.58-51.02% protection and 14.43-38.67%, respectively, in cotton
      pellet granuloma. There was a significant increase in analgesio-meter-induced
      force equivalent to 6.56-67.66% protection and 22.18-73.83% protection in acetic
      acid-induced writhing. The result establishes the traditional use of water
      decoction of Desmodium gangeticum codified in Indian System of Medicine.

PMID- 15507347
TI  - Possible mode of action of antiherpetic activities of a proteoglycan isolated
      from the mycelia of Ganoderma lucidum in vitro.
AB  - A bioactive fraction (GLPG) was extracted and purified from the mycelia of
      Ganoderma lucidum by EtOH precipitation and DEAE-cellulose column chromatography.
      GLPG was a proteoglycan and had a carbohydrate:protein ratio of 10.4:1. Its
      antiviral activities against herpes simplex virus type 1 (HSV-1) and type 2 (HSV
      2) were investigated by the cytopathic effect (CPE) inhibition assay in cell
      culture. This kind of polysaccharide inhibited the development of the cytopathic
      effect in dose-dependent manner in HSV-infected cells, moreover did not show any
      cytotoxic effects on cells even when a concentration was as high as 2000
      microg/ml. In order to study the possible mode of action of the antiviral
      activity of GLPG, cells were treated with GLPG before, during and after
      infection, and the viral titers in the supernatant of cell culture 48 h post
      infection were tested by TCID(50) assay. The antiviral effects in pre-treated and
      treated during virus infection with GLPG were more remarkable than the treatment
      of post-infection. Although the precise mechanism has yet to be defined, our work
      suggested that GLPG inhibits viral replication by interfering with the early
      events of viral adsorption and entry into target cells. Thus, this proteoglycan
      seems to be a potential candidate for anti-HSV agents.

PMID- 15507348
TI  - Antimycobacterial screening of some Turkish plants.
AB  - Extracts of 44 plant species distributed among 17 families from Turkey were
      screened against Mycobacterium tuberculosis H(37)Ra using microplate Alamar blue
      assay test. Six plants inhibited growth of M. tuberculosis H(37)Ra at 50
      microg/ml concentrations.

PMID- 15507350
TI  - Antimicrobial activity of Acalypha siamensis Oliv. ex Gage.
AB  - The hexane, dichloromethane, ethyl acetate and methanol fractions of leaves of
      Acalypha siamensis Oliv. ex Gage were evaluated for antibacterial and antifungal
      activity. The antibacterial activity was more pronounced in the ethyl acetate and
      methanol extracts. No activity was shown against tested moulds.

PMID- 15507349
TI  - Prospect for anthelminthic plants in the Ivory Coast using ethnobotanical
      criteria.
AB  - Sixty plant species were collected in the Ivory Coast on the basis of an
      ethnobotanical literature using the following three criteria: activity against
      worms, diarrhoea and/or abdominal pain. Eighty six plant extracts were prepared
      using 90% ethanol and tested for potential anthelminthic activities with a
      larvicidal test of Haemonchus contortus. 25.6% of the extracts showed a high
      activity, 12.8% were active or marginally active and the remaining 61.6% were
      inactive. The fact that a relatively high percentage of the plants species (50%)
      had an activity can be explained by the initial preselection of the plants on the
      basis of ethnobotanical indications.

PMID- 15507351
TI  - Traditional medicine in Sakarya province (Turkey) and antimicrobial activities of
      selected species.
AB  - Traditional medicine in North-West of Turkey (Sakarya province) were studied
      during a 2 months field study by interviewing local informants from several
      villages. Plant species used to treat infections were tested for antimicrobial
      activity. Information was collected for 46 plant species from 30 families and for
      5 animal species. Twenty four of the plant species were cultivated. Most used
      families were Asteraceae, Cucurbitaceae, Lamiaceae and Rosaceae and the most used
      plants were Artemisia absinthium, Equisetum telmateia, Lavandula stoechas,
      Melissa officinalis, Tussilago farfara and Urtica dioica. A total of 139
      medicinal uses were obtained. Plants are used mainly for infectious diseases
      (18%), for neurological and psychological disorders (13.7%), cardiovascular
      disorders (13%), skin disorders (12.2%) and respiratory disorders (10.1%).
      Extracts were tested in vitro for antimicrobial activity against Staphylococcus
      aureus ATCC 65538, Staphylococcus epidermidis ATCC 12228, Escherichia coli ATCC
      8739, Klebsiella pneumonia ATCC 4352, Pseudomonas aeruginosa ATCC 1539,
      Salmonella typhi, Shigella flexneri, Proteus mirabilis and Candida albicans ATCC
      10231, using microbroth dilution technique according to National Committee for
      Clinical Laboratory Standards (NCCLS). This research showed that Arum maculatum,
      Datura stramonium, Geranium asphodeloides and Equisetum telmateia petroleum ether
      extracts had MIC values of 39.1 microg/ml, 78.1 microg/ml, 78.1 microg/ml and
      39.1 microg/ml, respectively against Staphylococcus epidermidis. Datura
      stramonium petroleum ether extract had a MIC value of 39.1 microg/ml against
      Escherichia coli and Trachystemon orientalis ethanol extract had a MIC value of
      39.1 microg/ml against Escherichia coli. The antimicrobial activity of Arum
      maculatum, Equisetum telmateia, Geranium asphodeloides, Plantago intermedia,
      Senecio vulgaris and Trachystemon orientalis has been reported here for the first
      time.

PMID- 15507352
TI  - Chemical composition and antimicrobial activity of the essential oil of
      Cordiaverbenacea D.C.
AB  - Cordiaverbenacea D.C. (Boraginaceae) is found along the coastal regions of
      Brazil, from the Amazon basin to the southernmost state of Rio Grande do Sul. The
      aerial parts of this plant have been used in folk medicine since colonial times
      for their anti-rheumatic, anti-inflammatory, analgesic and healing properties.
      The objectives of this study were: the extraction of the essential oil of the
      aerial parts of this species and quantification of the yield thereof; the
      identification and quantification of the principal components of the essential
      oil; and the determination of its antimicrobial activity by plate diffusion
      method. The yield of essential oil was 0.19% (v/w) in relation to the fresh
      flowering aerial parts and 0.23% (v/w) of the leaves. The main constituents of
      the essential oil, identified by gas chromatography/mass spectrometry (GC/MS),
      were alpha-pinene (29.69%), trans-caryophyllene (25.27%) and aloaromadendrene
      (9.99%). The Gram-positive bacteria and yeast tested were sensitive to the
      essential oil of Cordiaverbenacea D.C., but most of the Gram-negative bacteria
      were resistant.

PMID- 15507353
TI  - Ions and amino acid analysis of Cyperus articulatus L. (Cyperaceae) extracts and
      the effects of the latter on oocytes expressing some receptors.
AB  - Extracts from rhizomes of Cyperus articulatus L. (Cyperaceae) used in Africa and
      Amazonia to treat many diseases has been shown to possess sedative and
      anticonvulsant properties. The aim of this study is to determine the mechanism of
      action of Cyperus articulatus extracts. In Xenopus oocytes expressing receptors,
      using electrophysiological measurement, extracts of rhizomes of Cyperus
      articulatus (300 microg/ml) inhibited 50% of the EC(50) and EC(80) of glutamate
      (1.3 and 2.9 microM, respectively) induced inward current through hNMDAR1A/2A
      receptors. Extracts induced very small current through rGluR3 receptors. The
      largest current induced by the extract (30 mg/ml) represents 128% of the EC(100)
      of glutamate induced inward current, through rGluR3 receptors. The excess 28%
      current could be induced by aspartate and/or glutamate in the extracts. The
      effect on Xenopus oocytes expressing heteromeric GABA(B)R1b/R2 receptors and
      rectifying potassium channels (Kir3) is clear. A decoction and water extract of
      Cyperus articulatus induced a large inward current that represented 71 and 57%
      (respectively) of the EC(100) of gaba (30 microM) induced inward current. The
      water extract induced also a large current through rectifying potassium channels
      (Kir3). Part of the current induced through GABA(B) receptors could be related to
      rectifying potassium channels and GABA(B) site receptors. Cyperus articulatus
      extracts possessed components that could decrease excitation (NMDA receptor
      antagonists) and increase inhibition (GABA(B) receptor agonists) in the central
      nervous system.

PMID- 15507354
TI  - Antinociceptive activities of aqueous and ethanolic extracts of Alpinia calcarata
      rhizomes in rats.
AB  - Rhizomes of Alpinia calcarata Roscoe (Zingiberaceae) posses several bio
      activities and are used in traditional medicine of Sri Lanka. However, their
      antinociceptive activity has not been investigated so far. The aim of this study
      therefore, was to examine the antinociceptive activity of hot water extract (HWE)
      and hot ethanol extract (HEE) of Alpinia calcarata rhizomes using rats and three
      models of nociception (tail flick, hot plate and formalin tests). Different
      concentrations of HWE (100, 250, 500, 750, 1000 mg/kg) and HEE (100, 250, 500,
      750, 1000 mg/kg) were made and orally administrated to rats and the reaction
      times determined. The results showed that the extracts have marked dose-dependent
      antinociceptive activity, when evaluated in the hot plate and the formalin tests
      but not in the tail flick test. The antinociceptive effect was slightly higher in
      HEE than that of HWE. The antinociceptive effect was mediated via opioid
      mechanisms.

PMID- 15507355
TI  - Environment and illness in the Calchaqui Valley (Salta, Argentina): phytotherapy
      for osteo-articular and cardio-circulatory diseases.
AB  - The aim of this work is to analyze and discuss the phytotherapy employed for two
      kinds of diseases, osteo-articular and cardio-circulatory, among the inhabitants
      of Molinos (Calchaqui Valley, Salta Province, Northwestern Argentina). These
      diseases take their origin in certain environmental conditions as well as the
      rural activities characteristic of the zone. The observations and interviews
      conducted among "medicos campesinos" (traditional healers) and the general
      population provided valuable information concerning the relationship between man
      and his environment, as it relates to health-illness processes. As a result of
      our research, we present a chart of the 25 recorded diseases and the 42 plant
      species employed in their therapy, considering the organs used, the ways of
      preparation and administration, as well as the geographic origin.

PMID- 15507356
TI  - Spasmogenic effect of a Solanummelongena leaf extract on guinea pig tracheal
      chains and its possible mechanism(s).
AB  - The methanol extract of fresh leaves of Solanum melongena L. (Solanaceae) was
      evaluated for its capacity to alter the tone of isolated, pre-contracted guinea
      pig tracheal chains, as well as for its possible mechanism(s) of action. Using
      serial dilutions between 0.0025 and 2.5 mg/mL, the extract was found to cause a
      dose-dependent increase in the force of muscle contraction. The EC(50) value was
      0.46 +/- 0.01 mg/mL. The concomitant use of acetylcholine 10(-5) M did not
      significantly affect the force of contraction induced by the extract. Histamine
      10(-5) M added at about 40% to, and salbutamol 10(-6) M antagonized by about 30%
      its constrictive effect. Chlorpheniramine 10(-6) M, propanolol 10(-5) M, and
      nifedipine 10(-6) M did not significantly influence the extract-induced force of
      contraction, but atropine 3 x 10(-7) M reduced it by approximately 60%. These
      data suggest that the Solanum melongena extract exerted a bronchospasmogenic
      rather than a bronchospasmolytic effect, probably through muscarinic receptor
      stimulation.

PMID- 15507357
TI  - Effects of Choto-san and hooks and stems of Uncaria sinensis on antioxidant
      enzyme activities in the gerbil brain after transient forebrain ischemia.
AB  - Previously, we revealed that oral administrations of Choto-san, a Kampo formula,
      and the hooks and stems of Uncaria sinensis Haviland (Rubiaceae), a medicinal
      plant comprising Choto-san, enhanced superoxide anion and hydroxyl radical
      scavenging activities in the hippocampus, and prevented delayed neuronal death of
      pyramidal cells in the hippocampal CA1 region in a transient forebrain ischemia
      gerbil model. In the present study, for the purpose of clarifying whether the
      endogenous antioxidant enzymes contribute to these mechanisms, we investigated
      the effects of Choto-san extract (CSE) and Uncaria sinensis extract (USE) on
      superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px)
      activities in the brain by using the same experimental model. 1.0% CSE or 3.0%
      USE were dissolved in water and provided to gerbils ad libitum from 7 days prior
      to ischemia/reperfusion (i/rp). Seven days of continuous administrations of CSE
      or USE without i/rp procedure enhanced CAT activity but not SOD and GSH-Px
      activities in both the hippocampus and cortex. CSE elevated CAT activity in the
      hippocampus at 7 days and in the cortex at 3h after i/rp. USE raised CAT activity
      in both the hippocampus and cortex at 3 h and 7 days after i/rp. These results
      suggest that one of the mechanisms of the protective effects of CSE and USE
      against transient brain ischemia-induced neuronal damage may be their enhancing
      effect on CAT activity in the brain.

PMID- 15507358
TI  - Preventive activity of pyrrolizidine alkaloids from Seneciobrasiliensis
      (Asteraceae) on gastric and duodenal induced ulcer on mice and rats.
AB  - The alkaloid extract of Senecio brasiliensis inflorescences contain a mixture of
      the pyrrolizidine alkaloids (PA) senecionine, integerrimine, retrorsine,
      usaramine and seneciphylline. We evaluated this PA mixture on preventive
      antiulcerogenic effects on standard rodent models of induced gastric and duodenal
      ulcers. In the HCl/ethanol, indomethacin-bethanechol and hypothermic-restraint
      induced gastric ulcer, the lesion was significantly inhibited by PA (p.o.) (p <
      0.001). In the pylorus-ligature, PA (i.d.), significantly increased the gastric
      juice content and the pH values and decreased the acid output. In the cysteamine
      induced duodenal ulcers, PA (p.o.) showed significant inhibition (p < 0.001) of
      the duodenal lesions when compared to the respective control. The levels of the
      somatostatin hormone in the blood samples of animals pre-treated with the PA
      (12.5 mg/kg) and the free mucus and prostaglandin synthesis also increased (p <
      0.001) after administration of PA extract (p.o.). The results suggested that the
      PA extract from Senecio brasiliensis inflorescences presents a significant anti
      ulcer effect in the selected ulcer models. The mechanism involved with the action
      of the PA extract is the cytoprotection. Additional studies are in progress to
      determine other possible mechanisms involved with effect of the PA as anti-ulcer
      agents.

PMID- 15507359
TI  - Studies on antibacterial, antioxidant and fibroblast growth stimulation of wound
      healing remedies from South Africa.
AB  - Aqueous and methanol extracts of Urtica urens, Capparis tomentosa, Dicoma
      anomala, Leonotis leonorus, Xysmalobium undulatum, Helichrysum foetidum,
      Pterocarpus angolensis, Terminalia sericea and Gunnera perpensa, plants
      documented as being used for topical wound healing in the literature, were tested
      for antibacterial activity against Staphylococcus aureus, Streptococcus pyogenes,
      Escherichia coli and Pseudomonas aeruginosa. Methanol and water extracts of two
      of these plants, Terminalia sericea and Gunnera perpensa, were more active
      compared to the other extracts against Streptococcus pyogenes and Staphylococcus
      aureus. The effects of the latter plants on fibroblast growth as well as oxidant
      production by N-formyl-methionyl-leucyl-phenylalanine were also studied. The
      water and methanol extracts of Terminalia sericea and Gunnera perpensa
      significantly decreased luciginin enhanced chemiluminescence at concentrations of
      100 microg/ml and higher. However, the extracts had no effect on the growth of
      primary human fibroblasts.

PMID- 15507360
TI  - Toxicological studies of the aqueous extract from Achyrocline satureioides (Lam.)
      DC (Marcela).
AB  - Achyrocline satureioides (Lam.) DC (Marcela) is known to possess a broad spectrum
      of pharmacological, medicinal and therapeutic properties. Previous studies have
      demonstrated various protective abilities of the marcela extracts against various
      pathological conditions. However, no extensive safety studies have been conducted
      on these extracts to date. In this paper, we evaluated the acute toxicity (dose
      levels of 30-300 mg/kg) of an aqueous extract of marcela, administered
      intraperitoneally and orally in mice and rats. The acute oral maximun tolerable
      dose in repeated administration during 4 h (1, 3 until 5 g/kg) was also studied
      in rats. The extract had low acute toxicity when administered intraperitoneally
      and no toxicity upon oral administration. The LD(50) of aqueous extracts of
      marcela was found to be greater than 5 g/kg when administered once via gastric
      intubation to rats. Weight gain, toxicity signs, enzymatic studies (transaminases
      and phosphatases) and histological evaluation of several organs indicated that
      the extract was devoid of acute toxicity. These acute studies demonstrated that
      an aqueous extract of marcela obtained after a 2% infusion is safe and did not
      cause any detrimental effects in vivo under the conditions investigated in this
      study.

PMID- 15507361
TI  - Diuretic effect of the aqueous extract of Bidens odorata in the rat.
AB  - The aerial part of Bidens odorata Cav., are used in Mexican Folk Medicine to
      treat renal diseases. The aim of this study is to measure the diuretic response
      to aqueous extract of this plant at doses of 41 and 166 mg/kg and to compare it
      with that induced by furosemide at 2 mg/kg. Aqueous extracts, furosemide or
      vehicle were administered orally to adult rats and the effects on sodium,
      potassium and water balance were assessed. Aqueous extracts at both doses and
      furosemide produced important and significant increments in urinary excretion of
      sodium, potassium and water in rats with respect to control group. This increase
      was dose dependent and aqueous extract at the highest dose induced a more marked
      sodium and water excretion than furosemide, potassium excretion increased but it
      was less than the one induced by furosemide. These results suggest that the
      aqueous extract of Bidens odorata induce diuretic response.

PMID- 15507362
TI  - Mycelial culture of Phellinus linteus protects primary cultured rat hepatocytes
      against hepatotoxins.
AB  - Hepatoprotective activity of Phellinus linteus was studied using H(2)O(2)- or
      galactosamine-injured primary cultures of rat hepatocytes as screening systems.
      The methanolic extract of the mycelial culture of Phellinus linteus significantly
      protected against hepatotoxins-induced toxicity in primary cultured rat
      hepatocytes as seen from the decreased level of glutamic pyruvic transaminase
      released from the injured hepatocytes. The methanolic extract of the mycelial
      culture of Phellinus linteus was subsequently fractionated with n-hexane, ethyl
      acetate, n-butanol and water. Among these fractions, 100 microg/mL of the ethyl
      acetate fraction was the most active one. The relative protections were 68.9 +/-
      5.3% in H(2)O(2)-injured hepatocytes and 46.8 +/- 3.9% in galactosamine-injured
      hepatocytes, respectively. The ethyl acetate fraction appeared to maintain the
      glutathione level which was decreased by the treatment of H(2)O(2) or
      galactosamine and restored the level of RNA synthesis more than two times
      compared to galactosamine-injured hepatocytes. These results suggest that the
      ethyl acetate fraction of the mycelial culture of Phellinus linteus protects
      hepatocytes from H(2)O(2)- or galactosamine-induced injury by maintaining hepatic
      glutathione level and RNA synthesis as well.

PMID- 15507363
TI  - Folk pharmaceutical knowledge in the territory of the Dolomiti Lucane, inland
      southern Italy.
AB  - An ethnopharmacognostic survey on the traditional pharmaceutical knowledge (TPhK)
      of old and newly introduced natural remedies used for healing humans in a small
      mountainous area in Central Lucania, inland southern Italy, was carried out using
      classical ethnographical and ethnobiological methods. Approximately 110 remedies
      of plant origin (belonging to 103 botanical taxa), 30 of animal origin and 20
      mineral or industrial (non-pharmaceutical) products were recorded. Among these
      remedies, the common use of the aerial parts of Hypericum hircinum and the leaves
      of Morus alba against cough, and the uncommon uses of Salvia argentea leaves as a
      haemostatic, of Erigeron acer roots to relieve tooth-aches and arthritic pains,
      and Elaphe quatuorlineata snake fat for rheumatism are reported for first time in
      Italy. Moreover, diverse medicinal plants used for uncommon medical purposes and
      a few biological ingredients used in food preparations with the aim to improve
      human health were identified. Pharmacological and toxicological considerations
      relating to possible applications of the recorded traditional knowledge in modern
      evidence-based medicine are discussed as well. The data that we present here
      could suggest new inputs for further phytochemical and pharmacological studies
      among Mediterranean folk pharmacopoeias, and also for sustaining environmentally
      integrated projects focused on of the maintenance of TPhK via breeding or
      controlled gathering activities of local medicinal species.

PMID- 15507364
TI  - Insulin-like effects of Bauhinia forficata aqueous extract upon Tityus serrulatus
      scorpion envenoming.
AB  - Scorpion envenoming causes an intense autonomic discharge, leading to a massive
      release of neurotransmitters, giving rise to several pathophysiological effects.
      In this work we report the effects of a Bauhinia forficata aqueous extract (BfAE)
      upon hyperglycemia, glycogenolysis, increase of plasma catecholamines, lethality
      and changes in serum insulin and plasma electrolytes induced by Tityus serrulatus
      scorpion venom (TSV). We compare them with the effects of the regular insulin
      therapy. The following treatments were performed: TSV (500 microg/kg, i.p.); BfAE
      (1g/kg, p.o.), 24, 12 and 1 h before and immediately after TSV or saline and
      insulin in a single dose (1.5 IU/kg, s.c.) after TSV. BfAE reduces the fast
      hyperglycemia induced by TSV, but it is deprived of hypoglycemic activity. The
      extract also did not reduce either the intense glycogenolysis or the release of
      catecholamines and did not stimulate the release of endogenous insulin, although
      causing changes in the electrolyte plasma levels similarly to insulin. Although
      BfAE and insulin antagonize some effects of TSV, they should be avoided in the
      treatment of Tityus serrulatus envenoming, since they enhance the lethality of
      the venom.

PMID- 15507365
TI  - Flavonoids with antinociceptive and anti-inflammatory activities from the leaves
      of Tilia argentea (silver linden).
AB  - Silver linden, Tilia argentea Desf. ex DC (Tiliaceae) leaves are used in the
      treatment of common cold and bronchitis. In order to evaluate this information,
      antinociceptive and anti-inflammatory activities of the two main flavonoid
      glycosides: kaempferol-3,7-O-alpha-dirhamnoside and quercetin-3,7-O-alpha
      dirhamnoside isolated from the leaves, were investigated. For the antinociceptive
      activity, p-benzoquinone-induced writhing test and for the anti-inflammatory
      activity, carrageenan-induced hind paw edema model in mice were used. Both
      compounds were shown to possess potent antinociceptive and anti-inflammatory
      activity at 50 mg/kg dose, per os, without inducing any apparent acute toxicity
      as well as gastric damage.

PMID- 15507366
TI  - In vitro antiplasmodial activity of callus culture extracts and fractions from
      fresh apical stems of Phyllanthus niruri L. (Euphorbiaceae): part 2.
AB  - The ethanolic extracts from fresh apical stems of Phyllanthus niruri L.
      (Euphorbiaceae) cultured on Murashige and Skoog (MS) medium supplemented with
      IBA/BAP/Coco nucifera L. milk for 1, 2, 4 and 6 months were phytochemically and
      biologically investigated and compared with intact plant part and whole plant
      extracts. Results from the in vitro antiplasmodial testing indicated that the
      EtOH extract of a 1-month-old callus culture (IC(50) = 16.3 +/- 2.5 microg/ml)
      exhibited a higher activity than the ethanolic extracts of the fresh apical stem
      (IC(50) = 18.2 +/- 2.4 microg/ml) and callus cultures of 2-, 4- and 6-months-old
      (25 microg/ml < IC(50) < 40 microg/ml). These activities were however lower than
      that displayed by the ethanolic extract of the whole plant (IC(50) < 3
      microg/ml). The EtOH extract of 1-month-old callus culture (the most active) was
      fractionated with solvents of different polarities. Its CH(2)Cl(2) fraction rich
      in terpenic constituents (IC(50) = 9.2 +/- 3.4 microg/ml) exhibited a higher
      antiplasmodial activity than its isoamylic alcohol fraction obtained at pH 2-3
      (IC(50) = 25.6 +/- 2.3 microg/ml) rich in flavonoids. The activity of these two
      fractions was lower than that displayed by the same fractions from the whole
      plant (2 microg/ml < IC(50) < 3 microg/ml). Alkaloidic fractions from the whole
      plant and 1-month-old callus culture of fresh apical stem were considered as
      inactive (IC(50) > 100 microg/ml).

PMID- 15507367
TI  - 3 Beta-(3,4-dihydroxycinnamoyl)-erythrodiol, a cytotoxic constituent of
      Zygophyllum geslini collected in the Algerian Sahara.
AB  - 3beta-(3,4-Dihydroxycinnamoyl)-erythrodiol was isolated as the cytotoxic
      constituent of the roots of Zygophyllum geslini.

PMID- 15507368
TI  - Metabolite profiling and chemopreventive bioactivity of plant extracts from
      Bidens pilosa.
AB  - Bidens pilosa has been used as a folk medicine in various medications and as a
      popular ingredient in herb teas. Chemopreventive activities of crude and
      fractionated plant extracts of Bidens pilosa were evaluated in this study. Ethyl
      acetate and butanolic fractions, partitioned from the total crude extract of
      Bidens pilosa, exhibited significant scavenging free radical activity (IC(50)
      values approximately = with 14-17 microg/mL) comparable to that of alpha
      tocopherol. Strong effects on the inhibition of LPS-mediated nitric oxide
      production in RAW 264.7 cells were also observed for the EA and BuOH fractions.
      Detectable cytotoxicity on RAW 264.7 cells, however, was observed for the EA
      fraction at a dose >100 microg/ml. The metabolite profile and major constituents
      of the BuOH fraction were studied and characterized using various spectroscopic
      analyses. A new compound, heptanyl 2-O-beta-xylofuranosyl-(1-->6)-beta
      glucopyranoside (1), and eight phenolic compounds, namely quercetin 3-O
      rabinobioside (2), quercetin 3-O-rutinoside (3), chlorogenic acid (4), 3,4-di-O
      caffeoylquinic acid (5), 3,5-di-O-caffeoylquinic acid (6), 4,5-di-O
      caffeoylquinic acid (7), jacein (8), centaurein (9) were for the first time
      isolated from Bidens pilosa. Compounds 2-7 are the major antioxidative
      constituents in the Bidens pilosa extract.

PMID- 15507369
TI  - Hepatoprotective and free radical scavenging activities of phenolic petrosins and
      flavonoids isolated from Equisetum arvense.
AB  - Hepatoprotective activity-guided fractionation of the MeOH extract of Equisetum
      arvense L. (Equisetaceae) resulted in the isolation of two phenolic petrosins,
      onitin (1) and onitin-9-O-glucoside (2), along with four flavonoids, apigenin
      (3), luteolin (4), kaempferol-3-O-glucoside (5), and quercetin-3-O-glucoside (6).
      Among these, compounds 1 and 4 exhibited hepatoprotective activities on tacrine
      induced cytotoxicity in human liver-derived Hep G2 cells, displaying EC(50)
      values of 85.8 +/ -9.3 microM and 20.2 +/- 1.4 microM, respectively. Silybin,
      used as a positive control, showed the EC(50) value of 69.0 +/- 3.3 microM.
      Compounds 1 and 4 also showed superoxide scavenging effects (IC(50) = 35.3 +/-
      0.2 microM and 5.9 +/- 0.3 microM, respectively) and DPPH free radical scavenging
      effect (IC(50) of 35.8 +/- 0.4 microM and 22.7 +/- 2.8 microM, respectively).
      These results support the use of this plant for the treatment of hepatitis in
      oriental traditional medicine.

PMID- 15507370
TI  - Inhibitory activity of Chrysanthemi sibirici herba extract on RBL-2H3 mast cells
      and compound 48/80-induced anaphylaxis.
AB  - The effects of extracts from various oriental medicinal herbs on mast cell
      mediated allergic reaction were investigated. Among them, Chrysanthemi sibirici
      herba ethanol extract exerted the potent inhibitory activity on antigen-induced
      degranulation in RBL-2H3 mast cells. Chrysanthemi sibirici herba dose-dependently
      inhibited DNP-BSA or compound 48/80-induced degranulation in RBL-2H3 mast cells,
      with IC(50) values of approximately 49 microg/ml and 76 microg/ml, respectively.
      This extract strongly suppressed compound 48/80-induced systemic anaphylaxis by
      48.7% at a dose of 300 mg/kg in mice. Chrysanthemi sibirici herba also inhibited
      the expression of TNF-alpha and the activation of the MAP kinase, ERK1/2, which
      is critical for the production of inflammatory cytokines in mast cells, as
      indicated by the suppression of activating phosphorylation of ERK1/2. These
      results lead us to conclude that Chrysanthemi sibirici herba may be used
      clinically to treat various allergic diseases.

PMID- 15507371
TI  - Effects of Papaver rhoeas extract on the expression and development of morphine
      dependence in mice.
AB  - The problem of drug dependence still remains unresolved. In the present study,
      the effects of water-alcohol extract of Papaver rhoeas on the expression and
      acquisition of naloxone-induced jumping and diarrhea in morphine-dependent mice
      were investigated. Administration of three daily doses of morphine (12.5, 25 and
      50 mg/kg) for three days in order to develop dependence to morphine caused a
      significant and dose-dependent increase in the number of jumping and diarrhea
      when the animals were challenged with naloxone (4 mg/kg). On the other hand,
      administration with the plant extract (25, 50 and 100 mg/kg) did not show any
      effect. Injection of extract (25, 50 and 100 mg/kg) 30 min before the naloxone
      administration in morphine-dependent mice decreased the number of jumping and
      diarrhea. Administration of extract (25, 50 and 100 mg/kg) 30 min before morphine
      injection increased the number of jumping but decreased the diarrhea. It could be
      concluded that the extract of Papaver rhoeas can ameliorate the withdrawal
      syndrome in morphine-dependent mice. Therefore, the extract might be useful to
      treatment of withdrawal signs in opioid addicts.

PMID- 15507372
TI  - Mutagenic and antioxidant activities of Croton lechleri sap in biological
      systems.
AB  - The sap of Croton lechleri Muell.-Arg (Euphorbiaceae), called Dragon's blood, is
      used in folk medicine as a cicatrizant, anti-inflammatory and to treat cancer. In
      this research, the antioxidant activity of Croton lechleri sap was evaluated
      against the yeast Saccharomyces cerevisiae and against maize plantlets treated
      with the oxidative agents apomorphine and hydrogen peroxide. The mutagenic
      activity of the sap was also analyzed using the Salmonella/microsome assay
      (Salmonella typhimurium TA97a, TA98, TA100, TA102, TA1535) and in cells of the
      yeast Saccharomyces cerevisiae. The results showed that Croton lechleri sap
      possesses significant antioxidant activity against the oxidative damages induced
      by apomorphine in Saccharomyces cerevisiae under all the conditions studied.
      However, in the case of hydrogen peroxide, antioxidant activity of the sap was
      detected only in cells in the stationary phase of growth. The sap was also able
      to protect cells of the maize plantlets from the toxic effect of apomorphine.
      This sap showed mutagenic activity for strain TA1535 of Salmonella typhimurium in
      the presence of metabolic activation and a weak mutagenic activity for strain
      TA98. These strains detect base pair substitutions and frameshift mutations,
      respectively. Mutagenicity was also observed in a haploid Saccharomyces
      cerevisiae strain XV185-14c for the lys1-1, his1-7 locus-specific reversion and
      hom3-10 frameshift mutations.

PMID- 15507373
TI  - Effects of various Eleutherococcus senticosus cortex on swimming time, natural
      killer activity and corticosterone level in forced swimming stressed mice.
AB  - The cortex of Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. has been used
      extensively in Russia, China, Korea and Japan as an adaptogen whose properties
      are the ability to increase as non-specific body resistance to stress and
      fatigue. Although it has been reported that Eleutherococcus senticosus has anti
      fatigue and anti-stress actions, their actions are still unclear on the
      relationship between immune system, especially natural killer (NK) activity and
      endocrine system (corticosterone level). We compared the effects of the water
      extracts (A, B, C, D and E) of five Eleutherococcus senticosus cortex on the
      swimming time, NK activity and blood corticosterone level using forced swimming
      stressed mice. Among five kinds, C, D and E extracts significantly prolonged the
      swimming time. C and D extracts inhibited the reduction of NK activity and the
      corticosterone elevation induced by forced swimming. The contents of
      eleutheroside E, isoflaxidin and eleutherosides B plus E were in the order C > D
      > E > B > A and C > E > D > A > B extracts, respectively. Therefore, it is
      suggested that eleutheroside E may be contributed to the anti-fatigue action, the
      recovery of the reduction of NK activity and the inhibition of corticosterone
      elevation induced by swimming stress.

PMID- 15507374
TI  - Antimalarial activity of lactucin and lactucopicrin: sesquiterpene lactones
      isolated from Cichorium intybus L.
AB  - Folklore reports from Afghanistan prior to the wars described the use of aqueous
      root extracts of Cichorium intybus (L.) as a light-sensitive plant remedy for
      malaria. Preparative isolation and bioassay against HB3 clone of strain Honduras
      1 of Plasmodium falciparum identified the previously known light-sensitive
      sesquiterpene lactones Lactucin and Lactucopicrin to be antimalarial compounds.

PMID- 15507375
TI  - Effects of exposure to diesel exhaust particles (DEP) on pulmonary metabolic
      activation of mutagenic agents.
AB  - Exposure of rats to diesel exhaust particles (DEP) or carbon black (CB) has been
      shown to induce time-dependent changes in CYP1A1and CYP2B1 in the lung. The
      present study evaluated the role of these metabolic enzymes on the pulmonary
      bioactivation of mutagens. Male Sprague-Dawley rats were intratracheally
      instilled with saline (control), DEP or CB (35 mg/kg body weight) and sacrificed
      at 1, 3, or 7 days post-exposure. Both control and exposed lung S9 increased the
      mutagenic activity of 2-aminoanthracene (2-AA), 2-aminofluorene (2-AF), 1
      nitropyrene (1-NP), and the organic extract of DEP (DEPE) in Ames tests with
      Salmonella typhimurium YG1024 in a dose-dependent manner. Lung microsomes
      prepared form control or particle-exposed S9, but not cytosolic protein,
      activated 2-AA mutagenicity. Compared to saline controls, CB-exposed S9 was a
      less potent inducer of 2-AA mutagenicity at all time points, whereas DEP-exposed
      S9 was less potent than control saline at 3 and 7 days but not 1 day post
      exposure. At 3 days post-exposure, DEP- or CB-exposed lung S9 did not
      significantly affect the mutagenicity of DEPE or 1-NP, when compared to the
      controls. The mutgenicity of 2-AA, 2-AF, 1-NP, and DEPE were significantly
      decreased in the presence of inhibitors for CYP1A1 (alpha-naphthoflavone) or
      CYP2B (metyrapone), but markedly enhanced by CYP1A1 or CYP2B1 supersomes with all
      the cofactors, suggesting that both CYP1A1 and CYP2B1 were responsible for
      mutagen activation. These results demonstrated that exposure of rats to DEP or CB
      altered metabolic activity of lung S9 and S9 metabolic activity dependent mutagen
      activation. The bioactivation of mutagens are metabolic enzyme- and substrate
      specific, and both CYP1A1 and CYP2B1 play important roles in pulmonary mutagen
      activation.

PMID- 15507376
TI  - Cisplatin disrupts mammalian spermatogenesis, but does not affect recombination
      or chromosome segregation.
AB  - Meiotic recombination is initiated by a series of double-strand breaks (DSBs) in
      areas of the genome that generally contain promoters and feature an open
      chromatin configuration [T.D. Petes, Meiotic recombination hot spots and cold
      spots, Nat. Rev. Genet. 2 (2001) 360-369]. To investigate whether induced DSBs
      likewise lead to recombinational repair and whether the placement of new exchange
      events alters normal patterns of recombination, we used the chemotherapeutic drug
      cisplatin (CP) to generate additional DSBs throughout the mouse genome. Treatment
      with CP impaired spermatogenesis, as exhibited by reductions in sperm counts,
      reductions in both testicular size and weight, changes in the distribution of
      cells at various prophase I substages, prolonged increases in germ cell
      apoptosis, and an increased incidence of synaptic abnormalities. Unexpectedly,
      however, no obvious effect on genome-wide recombination levels in CP-treated
      animals was observed, nor was the level of aneuploidy increased in sperm from
      exposed males.

PMID- 15507377
TI  - Unequal sister chromatid exchange in the rDNA array of Saccharomyces cerevisiae.
AB  - In the yeast Saccharomyces cerevisiae the nucleolar organiser region (NOR) is
      located on chromosome XII. It contains 100-200 copies of rDNA--a minimum of 20
      rDNA genes in tandem--and is termed the RDN locus. Yeast cells may exist in
      either haploid or diploid form. There are two forms of life cycle: haploid and
      diploid cells double by mitosis, and diploid cells are reduced to the haploid
      state by meiosis. Diploid cells have two homologous chromosomes for each of the
      16 chromosomes. They are usually of the same size. However, in this study it is
      shown that homologous chromosomes XII can become different in size due to unequal
      sister chromatid exchange during mitosis in 'old' cells.

PMID- 15507378
TI  - Lack of DNA damage induction by okadaic acid, a marine toxin, in the CHO-Hprt and
      the in vitro UDS assays.
AB  - Okadaic acid (OA) is a marine toxin produced by dinoflagellates and responsible
      for human intoxications. OA is a specific inhibitor of serine/threonine protein
      phosphatases PP1 and PP2A and a potent tumor promoter in mouse skin and rat
      glandular stomach. In a previous study, we demonstrated that OA induced
      aneuploidy in CHO-K1 cells using the cytokinesis-block micronucleus (CBMN) assay
      coupled to FISH and concluded that OA was not a direct mutagen. As some previous
      in vitro mutagenicity studies had given positive results with OA, we decided to
      perform two additional in vitro mutagenicity assays in accordance with the OECD
      guidelines: (i) the CHO/Hprt test, which provides end points about locus-specific
      gene mutation; (ii) the in vitro unscheduled DNA synthesis (UDS) assay in rat
      hepatocytes, which measures [(3)H]thymidine incorporation into DNA undergoing
      excision repair. In the CHO/Hprt assay, there was no significant increase in the
      number of mutants for doses ranging from 5 to 5000 nM in the presence or absence
      of rat liver S9 fraction. In the in vitro UDS assay, OA did not induce primary
      DNA damages in rat hepatocytes following 18 h exposure at concentrations between
      1.32 and 100 nM. As OA could affect the DNA repair systems via the inhibition of
      protein phosphatases, its effects on the repair kinetic of 2AAF-induced DNA
      damage were also investigated with the UDS assay. The results showed that OA did
      not interact with the DNA-repair process involved in in vitro UDS in rat
      hepatocytes. We concluded that OA failed to induce direct DNA damage but acted
      principally by altering the chromosome number, which could contribute to its
      carcinogenic effect.

PMID- 15507379
TI  - Analysis of mutagenic activity of airborne particulate matter, standard reference
      materials and reference compounds using base pair-specific Salmonella typhimurium
      tester strains.
AB  - The mutagenicity profiles of organic extracts of airborne dust samples from
      Mannheim, Germany, and two standard reference materials (SRM) as well as eight
      compounds with different chemical properties were investigated using tester
      strains Salmonella typhimurium TA700x (Ames II Assay). Each strain of this series
      carries a unique missense mutation in the histidine operon and is reverted by
      only one specific base substitution out of six possible changes. Mutation
      patterns of eight compounds with different modes of genotoxic action reveal
      significant differences. Samples of airborne particulate matter (APM) from an
      industrialized town in Germany (Mannheim) were collected for five consecutive
      days once a month for 1 year using an automatic high-volume air sampler. Samples
      taken from Monday to Friday were Soxhlet-extracted and prepared according to
      standard methods. Although the threshold limit for the least active strains is
      not triggered by all samples, it can be concluded that mutation patterns of the
      samples do not vary between different seasons. Standard reference materials
      (SRMs) were prepared and tested using the same methods. SRMs and APM samples from
      Mannheim reveal similar mutagenicity profiles in TA700x strains. The comparison
      of the mutagenicity profiles of air dust extracts from Mannheim and the SRMs,
      respectively, with reference compounds investigated so far shows some
      similarities although the patterns do not fit perfectly. Mutagenicity profiles of
      TA700x-activity of nitro-aromatic compounds published so far are similar to those
      of APM collected in Mannheim, Germany, as well as to standard reference materials
      1648 and 1649.

PMID- 15507380
TI  - The assessment of genotoxic effects in lymphocyte cultures of infants treated
      with chloral hydrate.
AB  - Chloral hydrate is a sedative commonly used in pediatric medicine. It was
      evaluated for genotoxicity in cultured peripheral blood lymphocytes of infants
      who were given chloral hydrate for sedation. Sister chromatid exchange and
      micronucleus frequencies were determined before and after chloral hydrate
      administration. After treatment, the frequencies of sister chromatid exchange and
      micronuclei were significantly increased, suggesting that chloral hydrate has
      moderate genotoxic potential in infants.

PMID- 15507381
TI  - Trichlorfon predisposes to aneuploidy and interferes with spindle formation in in
      vitro maturing mouse oocytes.
AB  - The pesticide trichlorfon (TCF) has been implicated in human trisomy 21, and in
      errors in chromosome segregation at male meiosis II in the mouse. We previously
      provided evidence that TCF interferes with spindle integrity and cell-cycle
      control during murine oogenesis. To assess the aneugenic activity of TCF in
      oogenesis, we presently analysed maturation, spindle assembly, and chromosome
      constitution in mouse oocytes maturing in vitro in the presence of 50 or 100
      microg/ml TCF for 16 h or in pulse-chase experiments. TCF stimulated maturation
      to meiosis II at 50 microg/ml, but arrested meiosis in some oocytes at 100
      microg/ml. TCF at 100 microg/ml was aneugenic causing non-disjunction of
      homologous chromosomes at meiosis I, a significant increase of the hyperploidy
      rate at metaphase II, and a significant rise in the numbers of oocytes that
      contained a 'diploid' set of metaphase II chromosomes (dyads). TCF elevated the
      rate of precocious chromatid segregation (predivision) at 50 and 100 microg/ml.
      Pulse-chase experiments with 100 microg/ml TCF present during the first 7 h or
      the last 9 h of maturation in vitro did not affect meiotic progression and
      induced intermediate levels of hyperploidy at metaphase II. Exposure to > or =50
      microg/ml TCF throughout maturation in vitro induced severe spindle aberrations
      at metaphase II, and over one-third of the oocytes failed to align all
      chromosomes at the spindle equator (congression failure). These observations
      suggest that exposure to high concentrations of TCF induces non-disjunction at
      meiosis I of oogenesis, while lower doses may preferentially cause errors in
      chromosome segregation at meiosis II due to disturbances in spindle function, and
      chromosome congression as well as precocious separation of chromatids prior to
      anaphase II. The data support evidence from other studies that TCF has to be
      regarded as a germ cell aneugen.

PMID- 15507382
TI  - In vitro potential genotoxic effects of surface drinking water treated with
      chlorine and alternative disinfectants.
AB  - A battery of in vitro short-term tests revealing different genetic end-points was
      set up in order to study surface-water genotoxicity after disinfection with
      different biocides: sodium hypochlorite (NaClO), chlorine dioxide (ClO(2)) and
      peracetic acid (PAA). The surface water both before and after disinfection was
      concentrated by adsorption on C(18) silica cartridges and the concentrates
      containing non-volatile organics were divided into different portions for
      chemical analyses and biological assays. The following in vitro tests were
      conducted on the water concentrates dissolved in DMSO: the Salmonella
      mutagenicity assay with S. typhimurium strains TA98 and TA100; the SOS Chromotest
      with Escherichia coli, the Microtox and Mutatox assays with Vibrio fischeri; and
      gene conversion, point mutation and mitochondrial DNA mutability assays with D7
      diploid Saccharomices cerevisiae strain. The results show that the SOS Chromotest
      and the yeast assays are highly sensitive in detecting genotoxicity. The surface
      water extracts were very often toxic to most of the test organisms considered,
      partially masking their potential mutagenic activity. Therefore, the assays with
      E. coli and with S. cerevisiae are more likely to show a mutagenic effect because
      these organisms are generally less sensitive to most toxic compounds. Among the
      tested disinfectants, NaClO and ClO(2) increased water genotoxicity, whereas PAA
      was able to slightly reduce raw water activity. However, because the organic
      compounds in the lake water varied with the season of the year, the disinfection
      processes, at times, both increased and decreased the raw water activity.

PMID- 15507383
TI  - Chromosome analysis of mouse zygotes after injecting oocytes with spermatozoa
      treated in vitro with green tea catechin, (-)-epigallocatechin gallate (EGCG).
AB  - The cytogenetic effects of (-)-epigallocatechin gallate (EGCG) on mouse
      spermatozoa were studied in vitro using an intracytoplasmic sperm injection
      (ICSI) technique. Spermatozoa were collected by the swim-up method and treated
      with EGCG at 1 microM and 10 microM. When motile, EGCG-treated spermatozoa were
      injected into oocytes, structural chromosome aberrations (SCAs) at the first
      cleavage metaphase did not increase significantly. However, a majority of
      immotile spermatozoa treated with 10 microM EGCG had the following abnormalities:
      pronuclear arrest (11% of activated oocytes), degenerated sperm chromatin
      (chromosome) mass (30% of activated oocytes) and occurrence of structural
      chromosome aberrations (57% of analyzed metaphases). The incidence of these
      abnormalities suggests that immotile spermatozoa were susceptible to EGCG, and
      that the damage of sperm chromatin was accelerated in immotile spermatozoa by 10
      microM EGCG treatment.

PMID- 15507384
TI  - The role of inducible co-stimulator (ICOS) in immunodeficiency.

PMID- 15507385
TI  - Estrogen as an immunomodulator.
AB  - Estrogen's role in the sex differences observed in autoimmune diseases such as
      systemic lupus, multiple sclerosis, and rheumatoid arthritis have remained
      unclear. Complicating the understanding of the immunomodulatory effects of
      estrogen are (1) the effects of estrogen on multiple components of the immune
      response; (2) its varied effects on different systems in which it appears pro
      autoimmune, as in murine lupus, or anti-inflammatory, as in EAE; and (3) its
      effects on other hormones which are potentially immunomodulatory. Recent reports
      have shed light on the role of estrogen in the modulation of lymphocyte survival
      and expansion and in the elaboration of Th1 versus Th2 cytokines and on the
      mechanisms by which estrogen can activate via multiple signaling and genomic
      pathways in immune cells.

PMID- 15507386
TI  - Swelling isn't swell.

PMID- 15507387
TI  - ICOS deficiency in patients with common variable immunodeficiency.
AB  - Common variable immunodeficiency (CVID) is the most frequent clinically
      significant primary antibody deficiency in man, predisposing to recurrent
      bacterial infections. Recently, we showed that the homozygous loss of the
      inducible costimulator (ICOS) on activated T cells may result in an adult onset
      form of CVID with autosomal recessive inheritance (AR-CVID). We screened 181
      sporadic CVID patients and 13 CVID patients from nine families with AR-CVID for
      mutations in ICOS by genomic DNA sequencing. In the AR-CVID families, the genomic
      integrity of the ligand for ICOS (ICOS-L) was also evaluated. In two of the nine
      AR-CVID families, we identified five individuals with ICOS deficiency, carrying
      the identical large genomic deletion of ICOS as previously described. In the
      remaining seven AR-CVID families, we subsequently sequenced the coding region of
      the ICOS ligand but found no mutations. The incidence of ICOS deficiency among
      patients with CVID is less than 5%. Worldwide, there are now a total of nine
      patients diagnosed with ICOS deficiency most likely due to a common founder. ICOS
      L deficiency could not be identified in families with AR-CVID.

PMID- 15507388
TI  - Single-tube test for autoantibodies to glutamic acid decarboxylase and proinsulin
      as first-line screening for autoimmunity in adult-onset diabetic patients.
AB  - The aim of this work was develop a new combined radioligand-binding assay (RBA
      combi) for the rapid and simultaneous determination of two autoimmunity markers,
      GADA and PAA, known to be differentially distributed in young and in some adult
      diabetic patients. The methodology was applied to sera from 85 young type 1 and
      98 adult-onset diabetic patients with different marker profiles and insulin
      requirements, and to 53 normal control sera. Among type 1 diabetes sera used as
      autoimmunity controls, 100% of those with at least one positive marker by single
      methods and 17.7% of those with double negative markers were positive by RBA
      combi (RBA-combi+). Among sera from adult-onset diabetes, 100% of those PAA+
      (GADA+ or GADA-), 92.3% of GADA+/PAA-, and 1.3% of GADA-/PAA- were RBA-combi+. In
      conclusion, the new RBA-combi allowed the simultaneous detection of GADA and PAA
      markers with acceptable performance. Moreover, 16 out of 18 (88.9%) of adult
      patients RBA-combi+ evolved to insulin requirement, suggesting that this test is
      a valuable tool for assessing autoimmune processes associated to future
      impairment of insulin secretion.

PMID- 15507389
TI  - BAY 50-4798, a novel, high-affinity receptor-specific recombinant interleukin-2
      analog, induces dose-dependent increases in CD25 expression and proliferation
      among unstimulated, human peripheral blood mononuclear cells in vitro.
AB  - Interleukin-2 administration induces CD4 T cell expansion in HIV-infected
      patients, however, toxicity can limit dosing. BAY 50-4798 is a recombinant IL-2
      analog with >1000-fold specificity for the high-affinity IL-2 receptor. The
      effects of this compound on unstimulated human PBMC were evaluated. PBMC from
      HIV(-) and HIV(+) donors were cultured in vitro with incremental doses of BAY 50
      4798 or aldesleukin. CD25 expression and proliferation were evaluated with flow
      cytometry. Cytokine levels were measured by ELISA in culture supernatants. BAY 50
      4798 induced dose-dependent increases in CD25 expression and proliferation of T
      cells, NK, and B cells and showed selectivity for CD4 T cells expressing CD25.
      Induction of pro-inflammatory cytokines was also dose-dependent and was observed
      at the concentrations of BAY 50-4798 with the highest biologic activity. These
      data suggest that BAY 50-4798 can induce proliferation of unstimulated T cells
      but loss of T cell selectivity and induction of pro-inflammatory cytokines occur
      at concentrations exerting the highest biologic activity.

PMID- 15507390
TI  - Heterozygote AG variant of -596 A/G IL-6 gene polymorphism is a marker for
      cutaneous T-cell lymphoma (CTCL).
AB  - The aim of the study was to investigate possible associations of IL-6 gene
      polymorphisms (-596 A/G and -174 C/G) with cutaneous T-cell lymphoma (CTCL). In
      the case-control study, genotype distributions and allelic frequencies in two
      promoter IL-6 gene polymorphisms in the group of 63 Czech patients with CTCL were
      compared to those of 105 control non-CTCL subjects matched for age and sex. The
      IL-6 gene polymorphisms were determined by PCR with following restriction
      analysis. A significant difference of -596 A/G IL-6 genotype distribution was
      found between the CTCL patients and the controls (P = 0.002) with almost
      threefold odds ratio for the heterozygote (AG) genotype in CTCL patients (OR =
      2.64, P = 0.002). No significant differences in genotype distribution and/or
      allelic frequency of functional -174 C/G IL-6 gene polymorphism were observed.
      The double heterozygote AGCG of both IL-6 promoter polymorphisms was associated
      with CTCL (OR = 2.24, 95% confidence interval 1.17-4.28, P = 0.01). Thus, the
      heterozygote variant of -596 A/G promoter IL-6 polymorphism could be considered
      as a genotype marker for CTCL.

PMID- 15507391
TI  - Dendritic cells fused with human cancer cells: morphology, antigen expression,
      and T cell stimulation.
AB  - Fusion of human dendritic cells (DC) with tumor cells is an effective approach
      for delivering tumor antigens to DC, and DC/tumor fusion cells are potent
      stimulators of autologous T cells. However, the integration and morphology of
      DC/tumor fusion cells has not been examined. In the present study, we fused
      patient-derived DC to autologous breast or ovarian carcinoma cells. The fusion
      cells possessed the properties of both parent cells. After fusion, the cytoplasm
      of the two cells was integrated, whereas their nuclei remained separate entities.
      Colocalization of MUC1 peptide and HLA-DR molecules was observed on fusion cells
      under the immunoelectron microscope. Coculture of patient-derived peripheral
      blood mononuclear cells (PBMC) with DC/tumor fusion cells resulted in activation
      of CD4 and CD8 T cells as assessed by IFN-gamma secretion, HLA-A*0201-MUC1
      tetramer, and standard cytotoxic T lymphocyte (CTL) assays. The present study
      provides first evidence of integration of human DC and tumor cells and links
      their properties to T cell activation.

PMID- 15507392
TI  - Minocycline inhibits antigen processing for presentation to human T cells:
      additive inhibition with chloroquine at therapeutic concentrations.
AB  - The ability of minocycline to inhibit processing of tetanus toxoid (TT) for
      presentation to human T cells was tested. Peripheral blood antigen presenting
      cells (APC) were incubated with TT before or after addition of test compounds for
      4 h. APC were then fixed with paraformaldehyde, and added to autologous TT
      responsive T cell lines for a proliferation assay. Minocycline (0.1-0.4 mM) gave
      significant inhibition of T cell response to TT and was equivalent to
      chloroquine. Inhibition was not observed when TT was incubated with APC before
      minocycline, indicating that presentation of preprocessed antigen was not
      inhibited. Minocycline, doxycycline, and tetracycline all inhibited the
      proliferation of PBMC to TT. The combination of minocycline and chloroquine
      resulted in additive inhibition at clinically relevant levels of both drugs (3.7
      microM). This study suggests a novel immunosuppressive mechanism for minocycline,
      as well as possible additive anti-inflammatory effect when combined with
      chloroquine or hydroxychloroquine.

PMID- 15507393
TI  - The Th2 response as monitored by CRTH2 or CCR3 expression is severely decreased
      during septic shock.
AB  - The shift of T lymphocytes toward a Th2 profile during septic shock has been
      established on the basis of in vitro cytokine production. In the present study,
      the Th2 response was investigated at the level of cell surface marker expression
      (whole blood flow cytometry). In 58 patients with septic shock, we observed a
      reduced CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2
      cells) expression on Th2 lymphocytes and regulatory T cells in comparison with 39
      healthy volunteers. Eosinophils, which constitutively express CRTH2 in healthy
      individuals, also exhibited low levels of CRTH2 in patients. In addition,
      eosinophil CCR3 expression (eotaxin receptor, type 2 chemokine) was strongly
      correlated with CRTH2, suggesting thus an extended modulation of Th2 related
      molecules. Importantly, the persistence over time of low levels of CRTH2 or CCR3
      expression was found in nonsurvivors. We hypothesize that the restoration of
      CRTH2/CCR3 expression may be an indicator for optimal recovery after septic
      shock.

PMID- 15507395
TI  - Characterization of virus-specific CD8(+) effector T cells in the course of HIV-1
      infection: longitudinal analyses in slow and rapid progressors.
AB  - Studies in humans have provided evidence that CD8(+) T cells exhibit distinct
      phenotypical and functional properties dependent on virus specificity. It is not
      known how these T-cell phenotypes develop over the course of infection. Dynamics
      and properties of T cells specific for human immunodeficiency virus (HIV),
      cytomegalovirus (CMV), and Epstein-Barr virus (EBV) in HIV infection were
      investigated in relation to viral load. In rapid progressors, HIV-specific CD8(+)
      T cells were less differentiated early in infection and did not develop a more
      differentiated phenotype. In slow progressors, perforin expression of HIV
      specific CD8(+) T cells slightly increased over time. HIV and EBV loads were
      detectable in all individuals, while CMV load could not be detected. Thus, in
      individuals with progressive HIV infection, HIV-specific T cells are less
      differentiated already early in infection. This apparent block in differentiation
      may be partly caused by chronic viremia or lack of CD4(+) T-cell help.

PMID- 15507394
TI  - Recovery from and consequences of severe iatrogenic lymphopenia (induced to treat
      autoimmune diseases).
AB  - To ascertain the consequences of severe leukopenia and the tempo of recovery, we
      studied the immunity of 56 adult patients treated for multiple sclerosis or
      systemic sclerosis with autologous CD34 cell transplantation using extremely
      lymphoablative conditioning. NK cell, monocyte, and neutrophil counts recovered
      to normal by 1 month; dendritic cell and B cell counts by 6 months; and T cell
      counts by 2 years posttransplant, although CD4 T cell counts remained borderline
      low. Initial peripheral expansion was robust for CD8 T cells but only moderate
      for CD4 T cells. Subsequent thymopoiesis was slow, especially in older patients.
      Importantly, levels of antibodies, including autoantibodies, did not drop
      substantially. Infections were frequent during the first 6 months, when all
      immune cells were deficient, and surprisingly rare (0.21 per patient year) at 7
      24 months posttransplant, when only T cells (particularly CD4 T cells) were
      deficient. In conclusion, peripheral expansion of CD8 but not CD4 T cells is
      highly efficient. Prolonged CD4 lymphopenia is associated with relatively few
      infections, possibly due to antibodies produced by persisting pretransplant
      plasma cells.

PMID- 15507396
TI  - Defective tumor necrosis factor alpha-induced maturation of monocyte-derived
      dendritic cells in patients with myelodysplastic syndromes.
AB  - Myelodysplastic syndromes (MDS) are clonal stem cell disorders, characterized by
      ineffective and dysplastic hematopoiesis. MDS patients have a defective immune
      response manifested by increased susceptibility to bacterial infections,
      autoimmune phenomena, and high incidence of lymphoid malignancies. Presently, we
      investigated the phenotype and function of monocyte-derived dendritic cells
      (MoDC) in 23 MDS patients and 15 controls at different stages of differentiation
      using the maturation stimuli tumor necrosis factor-alpha (TNF-alpha) and LPS.
      Monocytes from MDS patients showed low potential to differentiate into dendritic
      cells (DC), as determined by low cell yield and CD1a expression. MDS-MoDCs
      exhibited low expression of mannose receptor and reduced endocytic capacity. MDS
      MoDCs showed a diminished response to TNF-alpha with low CD83, CD80, and CD54
      expression and allostimulatory capacity. In patients with 5q syndrome, monocytes
      and MoDCs were positive for the 5q deletion, suggesting their origin from the
      malignant clone. Our data indicate that MoDCs in MDS display quantitative and
      functional abnormalities that may contribute to the defective immune response of
      these patients.

PMID- 15507397
TI  - Analysis of children with type 1 diabetes in Korea: high prevalence of specific
      anti-islet autoantibodies, immunogenetic similarities to Western populations with
      "unique" haplotypes, and lack of discrimination by aspartic acid at position 57
      of DQB.
AB  - This study analyzed the expression of anti-islet autoantibodies and HLA-DR and 
      DQ genotypes in Korean children with type 1 diabetes mellitus (T1DM). The
      positivity of the anti-ICA512, anti-GAD65, and anti-insulin autoantibodies in the
      newly onset T1DM patients (n = 15) was 66.7%, 86.7%, and 46.7%, respectively, and
      all of them had one or more of the autoantibodies. HLA analysis showed higher
      frequencies of HLA-DRB1*0301, *0405, *09012 and -DQB1*0201, *0401, *03032 alleles
      in T1DM patients compared to controls (P(c) < 0.05). Because HLA-DQB1*0401,
      *03032 alleles carry aspartic acid at position 57 of DQB, susceptibility to T1DM
      in Korean children was not related to the presence of aspartic acid at position
      57 of DQB1 locus. We suggest this unique HLA-DR, -DQ allele distribution might be
      an important factor for the low incidence of T1DM in Korea, and the combined anti
      islet autoantibody assays could be valuable screening markers for the early
      detection of T1DM in Korea.

PMID- 15507398
TI  - Biological role of Ep-CAM in the physical interaction between epithelial cells
      and lymphocytes in intestinal epithelium.
AB  - The mucosal epithelium including intestinal epithelial cells (IECs) and
      intraepithelial lymphocytes (IELs) provide a first line of defense in the
      gastrointestinal tract. However, limited information is currently available
      concerning the nature of the physical interaction molecule that interconnects
      IECs and IELs. Among the several monoclonal antibodies (mAbs) generated by
      immunizing porcine IECs, mAb (5-15-1) was shown to strongly react with IELs in
      addition to IECs. MALDI-TOF-MS and tandem MS analysis suggested that the antigen
      belongs to a family of human homophilic epithelial cell adhesion molecule (Ep
      CAM). The amino acid sequence of porcine Ep-CAM showed 82.8%, 78.1%, and 76.8%
      homology compared to human, mouse, and rat Ep-CAM. Moreover, 5-15-1 specifically
      reacted with transfectant of porcine Ep-CAM. These data suggest that the Ep-CAM
      may act as a physical homophilic interaction molecule between IELs and IECs at
      the mucosal epithelium for providing immunological barrier as a first line of
      defense against mucosal infection.

PMID- 15507399
TI  - In vitro cytokine production in patients with iron deficiency anemia.
AB  - The in vitro production of interleukin (IL)-1beta, IL-2, IL-6, IL-10, and tumor
      necrosis factor alpha (TNFalpha) by peripheral blood mononuclear cells (PBMC)
      from 20 patients with iron deficiency anemia (IDA) was examined before and after
      iron supplementation and compared to values obtained for PBMC from healthy
      controls. A significant decrease in IL-2 production was observed in IDA patients,
      whereas the secretion of the other cytokines did not differ from that of
      controls. Addition of iron to the culture medium did not affect the secretion of
      IL-2 and IL-1beta, but caused an increase in IL-6, IL-10, and TNF-alpha
      production. Since a deficiency in IL-2 production plays a role in the
      pathogenesis of certain infectious and malignant diseases, the results of the
      present study may explain in part the increased susceptibility to infections
      observed in patients with IDA.

PMID- 15507400
TI  - Evidence for protein kinase involvement in long-term postsynaptic excitation of
      intrinsic primary afferent neurons in the intestine.
AB  - We have investigated the effects of protein kinase inhibitors on the sustained
      slow postsynaptic excitation (SSPE) that is evoked by prolonged stimulation of
      synaptic inputs to intrinsic primary afferent neurons (IPANs) in the small
      intestines of guinea pigs. Stimulation of synaptic inputs to the IPANs caused
      depolarisation, increased input resistance, and increased excitation that
      continued after the cessation of stimulation. The excitation was substantially
      reduced by the broad-spectrum kinase inhibitor staurosporine (1 microM), PKC
      inhibitors Ro 31-8220 (3.3 microM) and calphostin C (1 microM), but not by the
      PKA inhibitor H89 (1 microM). At a higher concentration, 10 microM Ro 31-8220
      reduced the excitability of axons to electrical stimulation. Phorbol dibutyrate
      (1 microM) caused excitability increases, membrane depolarisation, and increased
      input resistance that mimicked the SSPE. We conclude that the generation of the
      SSPE requires a phosphorylation step that is mediated by protein kinase C.

PMID- 15507401
TI  - Responses of hepatic glucose output to electro-acupuncture stimulation of the
      hindlimb in anaesthetized rats.
AB  - Responses of hepatic glucose output (HGO) to electro-acupuncture (EA) stimulation
      of the hindlimb were investigated in anaesthetized rats, focusing on involvement
      of the somatic afferent and autonomic efferent nerves. HGO was measured with a
      microdialysis probe implanted into the left lateral lobe of the liver. Stainless
      steel needles with a diameter of 0.25 mm were inserted into the right tibialis
      anterior muscle and connected to an electrical stimulator. The EA stimulation was
      delivered for 10 min at 10 mA, 20 Hz. Atropine was injected in order to block the
      action of the parasympathetic nerves, whereas phentolamine and propranolol were
      injected in order to block the action of the sympathetic nerves. Furthermore,
      adrenal sympathetic nerves were crushed bilaterally to block the reflex secretion
      of adrenal medullary hormones. The EA stimulation significantly increased HGO for
      20 min after the onset of stimulation. The increases of HGO were abolished by
      severing the femoral and sciatic nerves, demonstrating that the responses are
      elicited via activation of somatic afferent nerves. Furthermore, the increases
      were diminished after severance of the adrenal sympathetic nerves, which regulate
      catecholamine secretion from the adrenal medulla. The increases were totally
      abolished after pretreatment with phentolamine, an alpha-adrenergic blocker, and
      propranolol, a beta-adrenergic blocker. On the other hand, the increases of HGO
      in response to the EA stimulation were augmented after pretreatment with
      atropine, a muscarinic cholinergic blocker. The present results demonstrate that
      EA stimulation to a hindlimb can reflexly increase HGO via activation of somatic
      afferents and, thereby, sympathetic efferents, including sympathetic efferents to
      the adrenal medulla. The present results further show that the increases of HGO
      in responses to EA stimulation are simultaneously reflexly inhibited via the
      parasympathetic nerves.

PMID- 15507402
TI  - Behavioral and autonomic dynamics during contextual fear conditioning in mice.
AB  - Aversive conditioning to contextual stimulation was performed in mice implanted
      with ECG transmitters to investigate heart rate (HR) and behavioral responses
      during contextual retention. The dynamics of HR were analyzed by advanced
      nonlinear techniques to uncover central neuroautonomic outflow inferred from its
      sympathetic (SNS) and parasympathetic (PNS) projection onto the sinus node of the
      heart. Mice experienced a single foot shock (US, unconditioned stimulus) either
      immediately (USi) or late (USl) after placement in the conditioning context.
      Contextual memory was tested 24 h after training by reexposure to the
      conditioning context for 32 min. Only mice that experienced the USl exhibited a
      pronounced and sustained behavioral suppression (immobility) indicative of
      conditioned contextual fear. In contrast, HR was initially close to its maximal
      physiological limit (approximately 800 bpm) in all groups, and recovery towards
      baseline levels was sluggish, the most pronounced delay observed in the USl
      group. The results demonstrate that behavioral immobility was associated with
      maximum activation of autonomic system output in response to contextual
      reexposure. However, advanced complexity analysis of the variability of HR
      revealed uniform or stereotyped dynamical properties that were interpreted to
      reflect a generalized state of anticipatory emotional arousal experienced during
      reexposure to contextual stimuli. It is concluded that the dynamics of HR is a
      highly sensitive index of the autonomic nervous system response and emotional
      state elicited by sensory stimulation of an unfamiliar environment.

PMID- 15507403
TI  - Effects of cooling and ARL 67156 on synaptic ecto-ATPase activity in guinea pig
      and mouse vas deferens.
AB  - We have studied the influence of temperature and ARL 67156 on ATP hydrolysis in
      mouse and guinea pig vas deferens in order to explore the properties of the
      enzymatic inactivation mechanism proposed to regulate purinergic
      neurotransmission at the sympathetic neuromuscular junction of smooth muscle. The
      ectonucleotidase activity was determined by using the malachite green method to
      measure the inorganic phosphate (Pi) liberated with ATP used as a substrate. ATP
      hydrolysis in both species was found to be insensitive to ouabain (100 microM),
      sodium azide (1 mM), sodium vanadate (100 microM) and beta-glycerophosphate (10
      mM) and was also found to depend on Ca2+ and Mg2+. V(MAX) of the ectonucleotidase
      activity for guinea pig and mouse vas deferens was 958.4+/-66.3 and 79.7+/-8.5
      pmol/min/mg, while K(M) was 625.1+/-45.2 and 406.0+/-29.0 microM, respectively.
      Cooling the tissues from 35 to 25 degrees C reduced the enzyme activity
      significantly (P<0.01) by 52.7+/-9.2% in guinea pig vas deferens and 34.9+/-5.3%
      in mouse vas deferens. ARL 67156 (100 microM), the specific ecto-ATPase
      inhibitor, caused a reduction in enzyme activity in guinea pig and mouse vas of
      54.1+/-16.4% and 53.0+/-7.6%, respectively (P<0.01). The degree of inhibition of
      ATP hydrolysis by lowered temperature and 100 microM ARL 67156 correlates well
      with the reported potentiation and prolongation of junction potentials under
      these conditions. It is concluded that ecto-ATPase or a closely related
      ectonucleotidase plays an important role in the physiological regulation of
      purinergic neurotransmission.

PMID- 15507404
TI  - Salsolinol, an antagonist of prolactoliberine, induces an increase in plasma
      catecholamine levels in the rat.
AB  - It has been recently observed that salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4
      tetrahydroisoquinoline), a putative endogenous prolactin-releasing factor is a
      potent inhibitor of stress-induced release of epinephrine and norepinephrine. The
      prolactin release caused by salsolinol was inhibited by 1-methyl-3,4
      dihydroisoquinoline (1MeDIQ). Therefore, the aim of our present studies was to
      investigate the effect of 1MeDIQ on plasma catecholamine levels. It has been
      found that 1MeDIQ is able to induce a massive increase in plasma catecholamine
      levels. Pretreatment of the animals with a ganglionic blocker, chlorisondamine,
      could completely abolish the effect of 1MeDIQ on plasma norepinephrine, and
      plasma epinephrine levels were only significantly attenuated. Spinal cord
      transection between cervical and thoracic segments eliminated 1MeDIQ induced
      increase in epinephrine, whereas increase in plasma norepinephrine was not
      affected. Hence, this effect of 1MeDIQ on sympathoadrenal system activity is most
      probably mediated through the level of sympathetic ganglia or partially at more
      centrally located sites of the nervous system. These results suggest that
      elevation of plasma catecholamines is involved in the mechanism of action of
      1MeDIQ inhibiting the biological effect of salsolinol.

PMID- 15507405
TI  - Organization of the newborn piglets vagal motor complex: insights into integrated
      autonomic control mechanisms.
AB  - Pediatric disorders frequently exhibit dysregulation of sympatho-vagal activity,
      and impaired control of cardiovascular vagal networks. Factors influencing the
      maturation of vagal networks are of special interest because they normally
      protect the heart and circulation, facilitate digestion, and preserve visceral
      metabolism. At present, scant literature exists regarding the development of
      vagal innervation of the heart. This study in neonatal swine, Sus scrofa, mapped
      the normal anatomy of vagal motor cell groups, with special focus on the origins
      of cardiomotor neurons. Right cardiac nerve branches, or the right thoracic vagal
      trunk were resected, inserted into capillary glass vials filled with 2%
      FluoroGold (FG) tracer solutions, and sealed to prevent leakage (false
      positives). Dorsal and ventral vagal complexes were identified on cross-sectioned
      tissues incubated in a well-characterized specific FG antibody. Thoracic and
      abdominal vagal motoneurons were cytologically heterogeneous, and predominantly
      medium-sized, polygonal cell bodies. Discrete longitudinal cell columns were
      observed, as well as organized arrays of elongate spindle-shaped cells in
      formation. Long axes and dendrites appeared to orient toward incoming peripheral
      sensory and central afferents, and were juxtaposed to cerebral microvasculature.
      The piglets' dorsal vagal complex is: (i) thick and long, comparable to
      ruminants, in contrast to much shorter lengths in non-ruminants, and (ii) the
      chief source of vagal motoneurons, forming discrete, topographically organized
      parasympathetic cell groups with distinct dendritic arbors. The cardiac motor
      subnucleus is localized to a highly restricted areal subunit of nucleus ambiguus'
      external formation in the vicinity of the obex. On the other hand, dorsal cardiac
      vagal motoneurons were few in number and diffusely distributed. Dorsal vagal
      motoneurons of neonatal swine likely projected primarily to the enteric nervous
      system, exerting excitatory influence over gastrointestinal activity.

PMID- 15507406
TI  - Intestinal infusions of oleate and glucose activate distinct enteric neurons in
      the rat.
AB  - Nutrients entering the small intestine trigger a variety of neural and endocrine
      reflexes that involve specific afferents, efferents and interneurons, many of
      which are located within the enteric nervous system (ENS). We hypothesized that
      intestinal nutrient stimuli might activate specific subpopulations of these
      neurons. To test this hypothesis, we utilized immunohistochemical detection of
      nuclear c-fos expression in the myenteric and submucosal plexuses of the rat
      small intestine following intraintestinal infusions of oleate or glucose.
      Additionally, we used dual label methods to detect both Fos-immunoreactivity and
      immunoreactivity for five phenotypic neuronal markers: neurokinin-1 receptor (NK
      1R), neurofilament-M (NF-M), neuronal nitric oxide synthase (NOS), calbindin
      (Cal) and calretinin (Calr), to characterize neurons that were activated by
      intestinal infusion of oleate and glucose. We found that oleate and glucose
      activated myenteric neurons in the duodenum and jejunum, but not the ileum.
      Oleate and glucose infusions significantly increased the number of Fos
      immunoreactive nuclei in the submucosal plexus of the duodenum and jejunum,
      however, only glucose increased Fos-immunoreactivity in the ileum. Oleate and
      glucose infusions were associated with a small increase in Fos-immunoreactivity
      in NOS-immunoreactive neurons in the myenteric plexus. In the submucosal plexus,
      the majority of neurons activated by intestinal infusion of oleate or glucose
      were immunoreactive to Cal and Calr. In the rat, many of these neurons have
      Dogiel Type II-like morphology, which is consistent with the possibility that
      these neurons function as mucosal afferents in reflexes activated by nutrient
      stimuli.

PMID- 15507407
TI  - Investigation of the effect of the c-kit inhibitor Glivec on isolated guinea-pig
      detrusor preparations.
AB  - In order to assess the possible role of the c-kit positive cells in the bladder,
      the effects of c-kit tyrosine kinase inhibitor, Glivec, on spontaneous excitation
      and ion channel activity in detrusor smooth muscles of the guinea-pig bladder
      were investigated using intracellular microelectrodes, isometric muscle tension
      recordings and patch clamp techniques. Glivec (10 microM) converted action
      potential bursts into continuous firing without affecting their shape but at 50
      microM abolished spontaneous action potentials. It had little effect on inward
      and outward currents at <10 microM, but inhibited them at >50 microM. Glivec
      decreased the amplitude of spontaneous contractions dose dependently. These
      results suggest that c-kit positive cells may play a role in modulating
      spontaneous electrical and mechanical activities. Drugs inhibiting the c-kit
      receptor may provide a new approach for treating the overactive bladder.

PMID- 15507408
TI  - Differential effects on gastrointestinal and hepatic vagal afferent fibers in the
      rat by the anti-cancer agent cisplatin.
AB  - Cisplatin, a cancer chemotherapy agent, like many toxins, produces emesis and
      nausea. Abdominal vagotomy, or treatment with 5-HT3 receptor antagonists, blocks
      cisplatin-induced emesis, which suggests that it produces (albeit indirectly)
      activation of 5-HT3 receptors on vagal afferent fibers. Cisplatin induces a large
      release of intestinal 5-hydroxytryptamine (5-HT) that enters the hepatic portal
      vein, which may activate vagal afferent fibers in the portal vein or liver to
      induce emesis or other side effects of treatment (e.g., reduced food intake).
      This study was conducted to assess the effects of cisplatin on gastrointestinal
      and portal vein/liver vagal afferent fibers by recording the neurophysiological
      responses of the common hepatic branch (CHB) of the vagus in the rat. The CHB
      contains vagal afferent fibers that innervate the gastrointestinal (GI) tract,
      portal vein, and liver. Cisplatin (10 mg/kg; jugular vein, j.v.) produced an
      increase in multi-unit CHB activity and this effect was blocked by a 5-HT3
      receptor antagonist (Y-25130, 0.8 mg, j.v.). Cutting the gastroduodenal branch
      (GDB), a sub-branch of the CHB that contains GI afferent fibers, resulted in a
      complete suppression of the multi-unit CHB discharge produced by cisplatin
      treatment. Single units that were cisplatin sensitive had their activity reduced
      by either 5-HT3 receptor antagonist treatment or cutting the GDB. Conversely,
      cisplatin insensitive units were not affected by 5-HT3-antagonism or GDB
      ablation. The present results indicate that cisplatin activates GI vagal afferent
      fibers via 5-HT3 receptors but does not affect portal vein/liver vagal afferent
      fibers, which indicates that intestinal but not hepatic afferent fibers are
      involved in the toxic effects of cisplatin.

PMID- 15507409
TI  - Coordination dynamics of circulatory and respiratory rhythms during psychomotor
      drive reduction.
AB  - A 0.15-Hz rhythm band in cutaneous blood oscillations in awake human subjects was
      studied in cardiovascular-respiratory time series of five subjects relaxing
      naively or practicing hypnoid relaxation (autogenic training, or AT). Time series
      analysis used nonlinear algorithms, time-frequency distribution (TFD), postevent
      scan (PES) method, and linear fast Fourier transform (FFT) algorithm. This 0.15
      Hz rhythm band caused phase synchronization with respiration at 1:2, 1:1, and 2:1
      integer number (n/m) ratios for extended periods. During wave epochs, the 0.15-Hz
      rhythm band was amplified, causing the 0.15-Hz rhythm band to also appear in
      interbeat intervals and arterial blood pressure fluctuations. If phase
      synchronization of the 0.15-Hz rhythm band with respiration was established at a
      1:1 integer number ratio, it was maintained and resulted in consensualization of
      all cardiovascular-respiratory oscillations at this frequency. Simultaneous
      cardiovascular and respiratory oscillations at about 0.1 Hz did not affect the
      appearance of the 0.15-Hz rhythm band in the photoplethysmography (PPG) signal.
      Recent evidence suggests the emergence of the 0.15-Hz rhythm band and n/m phase
      synchronization to result from nonequilibrium phase transitions operational in
      the network of lower brainstem neurons and associated parasympathetic neuronal
      effectors. These findings corroborate our notion of the 0.15-Hz rhythm band as a
      marker of the trophotropic mode of operation.

PMID- 15507410
TI  - Effect of parathormone on heart rate variability in hemodialysis patients.
AB  - INTRODUCTION: Parathormone (PTH) is a very potent uraemic toxin, which affects
      heart structure and function. PTH also plays the role in uraemic autonomic
      neuropathy (AN). The aim of the study was to investigate the relationship between
      high PTH level and AN assessed with frequency domain measures of heart rate
      variability (HRV). MATERIALS AND METHODS: A 24-h ECG was performed in 40 HD
      (F=19, M=21) patients aged 49+/-11 years, duration of HD therapy 37+/-30 months.
      Frequency domain measures of HRV were obtained according to European Society of
      Cardiology recommendations. Total spectral power (TP), high frequency band (HF)
      and low frequency band (LF) were computed as indexes of: total autonomic nervous
      system (ANS) activity, parasympathetic and sympathetic activities, respectively.
      LF/HF ratio was calculated. TP, HF, LF and LF/HF were expressed as natural
      logarithm. Patients were divided into two groups due to PTH level: PTH+ (PTH> or
      =275 pg/ml) and PTH- (PTH<275 pg/ml). RESULTS: The values of lnTP and lnLF were
      lower in patients PTH+ than in patients PTH- (6,58+/-0,76 vs. 6,99+/-0,44 ms2,
      p<0,05, and 4,91+/-0,99 vs. 5,33+/-0,65 ms2, respectively, p=0,06). We also found
      negative correlation between lnPTH and lnTP (r=-0,47; p<0,005), lnPTH and lnLF
      (r=-0,35; p<0,05), lnPTH and lnHF (r=-0,34; p<0,05). On multiple regression
      analysis, lnTP, lnLF and lnHF were independently related to lnPTH. CONCLUSIONS:
      Parathormone exerts effect on activity of both parts of autonomic nervous system:
      sympathetic and parasympathetic. High PTH level deteriorates total autonomic
      activity.

PMID- 15507411
TI  - Impact of the international subarachnoid aneurysm trial on radiology.

PMID- 15507412
TI  - PET technology: current trends and future developments.

PMID- 15507413
TI  - Dysplastic nodules in liver cirrhosis: detection with triple phase helical
      dynamic CT.
AB  - The purpose of this study was to determine the sensitivity of triple phase
      helical dynamic CT for detecting dysplastic nodules in patients with liver
      cirrhosis. 76 dysplastic nodules were confirmed by histopathological examination
      of the liver specimens after surgical resection in 21 patients or after
      explantation of the whole liver in 20 patients. Triple phase helical dynamic CT
      including arterial, portal venous and delayed phases was performed as a pre
      operative evaluation for hepatocellular carcinoma. Two readers retrospectively
      evaluated the images. The presence of dysplastic nodules was determined by one-to
      one correlation of the CT images and the pathological results in terms of the
      anatomical location and size of each nodule. Helical dynamic triple phase CT
      depicted eight of 76 dysplastic nodules (10%): five of 35 high grade dysplastic
      nodules (14%) and three of 41 low grade dysplastic nodules (7%). Triple phase
      helical dynamic CT is insensitive for detection of dysplastic nodules in
      cirrhotic livers.

PMID- 15507414
TI  - Focal bowel wall changes detected with colour Doppler ultrasound: diagnostic
      value in acute non-diverticular diseases of the colon.
AB  - We performed a study to determine if colour Doppler findings may help to identify
      the cause of wall thickening in acute non-diverticular diseases of the colon. The
      study group included 66 patients admitted to the emergency department with a
      final diagnosis of infectious colitis (n=23), inflammatory colitis (n=10),
      ischaemic colitis (n=23) and malignant tumours (n=10). The following ultrasound
      features were assessed: maximal wall thickness, wall stratification, arterial
      flow in the colonic wall and arteriolar resistive index. Higher values of wall
      thickness were observed in malignant tumour (18.2+/-6.2 mm, p<0.001). Moderately
      thickened wall (6.6+/-1.3 mm, p< or =0.06), preserved stratification (90% versus
      46% in the remainder of the study population) and lower resistive index (0.51+/
      0.10, p< or =0.05) were significantly related to inflammatory colitis. Absence of
      arterial flow was more frequently observed in ischaemia (43% versus 12% in the
      remainder of the study population). In conclusion, despite some overlap, both
      ultrasound and colour Doppler features are helpful in the differential diagnosis
      of colonic thickening related to non-diverticular colonic lesions.

PMID- 15507415
TI  - Phentolamine re-dosing during penile dynamic colour Doppler ultrasound: a
      practical method to abolish a false diagnosis of venous leakage in patients with
      erectile dysfunction.
AB  - Increased sympathetic tone may cause an equivocal response to a prostaglandin E1
      (PGE1) penile Doppler ultrasound (US) examination interpreted as a venous leak.
      We evaluated the US parameters and erectile response to the addition of
      phentolamine to a PGE1 penile Doppler US examination to ascertain whether
      addition of phentolamine would abolish a suboptimal response. 32 patients (median
      age 29 years, range 17-70 years) with either a previous Doppler US pattern of
      venous leakage or a clinical suspicion of venogenic impotence, underwent Doppler
      US after a total dose of 20 microg of PGE1. Peak systolic velocity (PSV), end
      diastolic velocity (EDV) and grade of erection were documented. If erectile
      response was suboptimal irrespective of the EDV measurement, 2 mg-intracavernosal
      phentolamine was administered and measurements repeated. Six patients had a
      normal erectile response, the remaining 26 received phentolamine. A significant
      increase in PSV between baseline and 20 microg PGE1 (p<0.001) was observed in all
      cases. Following phentolamine there was a significant increase in grade of
      erection (p=0.0001) and a significant reduction in the EDV (p=0.0001). A
      reduction of the EDV to below 0.0 cm s(-1) was observed in 16 patients. Four
      patients with EDV <5.0 cm s(-1) but >0.0 cm s(-1) had improved erectile response
      following phentolamine while six showed persistent EDV elevation >5 cm s(-1). No
      priapism was documented. It is essential to ensure cavernosal relaxation using
      phentolamine before a Doppler US diagnosis of venous leak is made. This two-stage
      assessment will allow this to be done efficiently and with a low risk of
      priapism.

PMID- 15507416
TI  - Evaluation of work practices and radiation dose during adult micturating
      cystourethrography examinations performed using a digital imaging system.
AB  - A micturating cystourethrography (MCU) examination is a specific radiological
      procedure that is performed under fluoroscopic screening to visualize the bladder
      by filling it with contrast material and to evaluate the urethral morphology
      during voiding. It is necessary to evaluate radiation dose during MCU examination
      since it involves radiosensitive organs such as the gonads. Radiation dose
      imparted to 109 patients undergoing MCU examination were measured using a dose
      area product (DAP) meter. Patients were categorized into two groups based on
      whether filling of the bladder with contrast medium was done retrogradely (MCU)
      or by the suprapubic percutaneous route (SP-MCU). The DAP values to Group A (MCU)
      and Group B (SP-MCU) patients varied from 0.43 Gycm(2) to 9.26 Gycm(2) and 0.54
      Gycm(2) to 9.87 Gycm(2), respectively. Reduction of radiation dose to patients
      was possible by the use of optimized exposure factors, precise collimation of X
      ray beam, use of 0.2 mm copper filters and by acquiring images digitally.

PMID- 15507417
TI  - Exposure variations under error conditions in automatic exposure controlled film
      screen projection radiography.
AB  - Improper automatic exposure control (AEC) termination may result in high
      overexposures on some radiographic systems. Under AEC, X-ray factors are adjusted
      automatically to compensate for differences in patient thickness and density. In
      radiography, AEC is implemented using ionization chambers placed in the film
      bucky. In this study we deliberately chose incorrect set-up conditions and
      assessed the response of the AEC system. Two types of incorrect set-up were
      studied: (1) incorrect selection of bucky radiation detector and (2) simulated
      misalignment between the X-ray field and light field. The systems tested varied
      in age from 1 year to in excess of 10 years. In the first test, overexposures of
      90 mGy were recorded. Two systems did not meet EC guidelines for improper AEC
      termination. The second test, misalignment of the X-ray field, was observed to
      affect the exposure delivered by approximately +/-22%. The maximum dose increase
      observed, with a chest phantom in the beam, was 165 microGy. Misalignments also
      resulted in reduced exposures, which may impact on image quality.

PMID- 15507418
TI  - Radiological parameters and radiation doses of patients undergoing abdomen,
      pelvis and lumbar spine X-ray examinations in three Nigerian hospitals.
AB  - Thermoluminescent dosemeters (TLDs) have been used to measure the entrance
      surface doses (ESDs) of patients undergoing pelvis, abdomen and lumbar spine
      diagnostic X-ray examinations in Nigeria. A total of three public hospitals and
      171 patients were included in this investigation. The ages of the patients
      involved were from 40 years to 85 years, while their weights ranged from 64 kg to
      73 kg. Mean, median, first and third quartiles of ESDs are reported. The results
      showed that in most cases, for each of the examinations, the individual ESD
      values are found to be comparable with, and higher than, those from Ghana and
      Tanzania, respectively. The mean ESD values are also found to be within the range
      of mean ESD values that have been previously been reported from countries outside
      Africa. When compared with the European Community (EC) reference values, the mean
      ESDs were found to be below the reference values in only two of the hospitals.
      The ranges found in this work are high and this indicates more attention needs to
      be given to X-ray facilities in the country. This also suggests that radiographic
      departments need to review their radiographic practices in order to bring their
      doses to optimum levels. Effective doses were also calculated from the ESD
      values. The mean effective doses were found to be generally low when compared
      with those found in the literature from other countries including two African
      countries. The radiographic parameters used for all the patients were also
      compared with the European criteria. It is recommended that the tube filtration
      at one hospital be increased. The importance of good regulatory activities and
      trained personnel is stressed in this work. Apart from the fact that the data
      provided in this work will be useful for the formulation of national guidance
      levels, they also provide patient dosimetry information on healthcare level IV
      countries.

PMID- 15507419
TI  - Equivalent diameters of elliptical fields.
AB  - The equivalent field method is well established as a means of performing dose
      calculations in rectangular and irregular fields. There is, however, no consensus
      on the equivalent diameter (D) of elliptical fields, despite their common
      applications in kilovoltage radiotherapy. Measurements have been performed on 15
      elliptical fields and 6 circular fields, comprising all possible combinations of
      3 cm, 4 cm, 5 cm, 6 cm, 9 cm and 12 cm diameters, using 150 kV X-rays, with a
      half-value thickness of 8 mmAl. Equivalent diameters were calculated by a number
      of methods, including the equal area, ratio of perimeter to area, 2AB/(A+B) and
      sector integration. The best agreement with measurement was obtained using sector
      integration, which agreed with measurements within the limits of experimental
      error. The formula D=2AB/(A+B) was the best of the analytic formulae; at shallow
      depths it gave predictions of dose within better than 0.5%, whilst at 5 cm deep
      its greatest error was 1.6%. The equal area formula (D = square root AB) gave the
      worst predictions, with errors up to 5% at shallow depths, and 9% at a depth of 5
      cm.

PMID- 15507420
TI  - Hepatic bipolar radiofrequency ablation using perfused-cooled electrodes: a
      comparative study in the ex vivo bovine liver.
AB  - The purpose of this paper was to demonstrate the efficacy of the dual probe
      bipolar radiofrequency (RF) system with the perfused-cooled electrodes inducing
      coagulation necrosis in the ex vivo bovine liver. The perfused-cooled electrode
      that allows simultaneous internal cooling and interstitial hypertonic saline
      perfusion has been developed for RF ablation (RFA). RF was applied to excised
      bovine liver in a bipolar mode at 150 W using a 200 W generator with two perfused
      cooled electrodes for 10 min. After placing the electrodes at 3 cm spacing in the
      explanted liver, 45 ablation zones were created with three different regimens:
      Group A, using both intraelectrode cooling and interstitial perfusion; group B,
      using only the intraelectrode cooling; and group C, using only interstitial
      perfusion. In groups A and C, RFA was performed with the infusion of 6%
      hypertonic saline at the rate of 2 ml min(-1). During RFA, we measured the tissue
      temperature at the midpoint between the two electrodes. The dimensions of the
      ablation zones and the changes in impedance, currents and liver temperature
      during RFA were compared in these three groups. The mean tissue impedance during
      RFA in group A (56.7+/-21.7 Omega) and group C (56.9+/-20.6 Omega) was
      significantly lower than group B (112+/-19.7 Omega) (p<0.001). The mean current
      was higher in group A (1765+/-128 mA) than groups B (760+/-321 mA) and C (1298+/
      349 mA) (p<0.05). In addition, the shortest vertical diameter of coagulation
      necrosis was greater in groups A (4.9+/-0.5 cm) and C (4.6+/-0.7 cm) than in
      group B (3.5+/-0.4 cm) (p<0.05). The temperature at the mid-point between the two
      probes was higher in group A than other groups: 99 degrees C in group A, 88.9
      degrees C in group B, and 94.3 degrees C in group C (p>0.05). The ratios of the
      diameter of the long-axis to the diameter of the vertical-axis of groups A, B and
      C were 1.1+/-0.1, 1.2+/-0.1, and 1.1+/-0.2, respectively (p<0.05). Bipolar RFA
      using intraelectrode cooling and the interstitial saline perfusion simultaneously
      produced ablation zones significantly larger than the area produced by only one
      measure.

PMID- 15507421
TI  - Technical note: a comparison of antiscatter grids for digital radiography.
AB  - The use of digital radiography (DR) systems offers a number of advantages over
      film-screen detectors. One potential disadvantage, however, is that some fixed DR
      systems do not allow the user to change the antiscatter grid to suit the imaging
      task. Instead, the user must choose the grid at the time of purchase. Six grids,
      which are offered as installation options for one commercial fixed-room DR
      system, were experimentally evaluated, using a range of scatter conditions and
      tube voltages. In addition, three grids, which are available with a portable DR
      system in which the user can change the grid to suit the imaging task, were also
      evaluated. The grids were compared using the primary transmission, scatter
      fraction, and calculated signal-to-noise improvement factor (SIF). It was found
      that the grids with low atomic number interspace and cover material had an SIF up
      to 15% higher than did the grids with aluminium interspace and cover material;
      the grid with a grid ratio of 12:1 had the highest SIF for all tube voltages and
      scatter conditions tested here. This 12:1 grid probably represents a good general
      purpose non-removable grid in DR.

PMID- 15507422
TI  - The kidney in paroxysmal nocturnal haemoglobinuria: MRI findings.
AB  - Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, acquired stem-cell disorder
      characterized by defective haematopoiesis, which results in an increased
      sensitivity of the erythrocytes to complement-mediated intravascular haemolysis.
      Renal damage is infrequent but can produce chronic renal failure due cortical
      deposits of haemosiderin and microvascular thrombosis. MRI provides
      characteristic images of the kidneys that enable haemosiderin deposition to be
      diagnosed; in PNH, MRI typically shows reversed renal cortex-medulla
      differentiation on T(1) weighted images and substantial loss of cortical signal
      intensity on both T(1) and T(2) weighted images. We describe the MRI findings of
      renal cortical haemosiderosis occurring in four patients with PNH.

PMID- 15507423
TI  - Giant renal capsular leiomyoma: study of two cases.
AB  - Leiomyomas of the renal parenchyma and of the capsule are rare. These tumours are
      normally small asymptomatic and often detected incidentally. Large renal
      leiomyomas can present with pain or as an abdominal mass, but they are rare. The
      imaging features of these tumours have been poorly described in the literature. A
      radiological distinction from other renal neoplasms is often difficult to make
      owing to the similarity of imaging findings. We report two patients with renal
      leiomyomas who presented with pain and an abdominal mass. Both patients underwent
      nephrectomy and histological evaluation confirmed the diagnosis of leiomyoma.

PMID- 15507424
TI  - Coexistence of lung cancer and tuberculoma in the same lesion: demonstration by
      high resolution and contrast-enhanced dynamic CT.
AB  - We report a case of coexistence of lung cancer and tuberculoma in the same
      lesion. The component parts of lung cancer and tuberculoma were identified on the
      basis of morphology on high-resolution CT as well as enhancement patterns and
      time-attenuation curves by contrast-enhanced dynamic CT.

PMID- 15507425
TI  - Intracranial laterally based supratentorial neurenteric cyst.
AB  - Neurenteric cysts are rare developmental cysts lined by endodermal derived
      epithelium. We present the case of a 68-year-old patient presenting with seizures
      who was found to have an extra-axial low density lesion with associated wall
      calcification on CT. Aspiration and biopsy of the cyst revealed a neurenteric
      cyst. Such lesions of the lateral supratentorial convexity are extremely rare and
      calcification has not been previously reported in these intracranial cysts.

PMID- 15507426
TI  - Intrahepatic portosystemic venous shunt passing through the left inferior phrenic
      vein and draining into the left renal vein.
AB  - We report a case of an intrahepatic portosystemic venous shunt (IPSVS) passing
      through the left inferior phrenic vein and draining into the left renal vein and
      then to the inferior vena cava. We incidentally detected the IPSVS while
      performing a transcatheter arterial embolisation for the treatment of
      hepatocellular carcinoma. IPSVS with the left inferior phrenic vein as the
      draining vein is very rare. The complete pathway of this IPSVS could be clearly
      demonstrated by multidetector row CT during arterial portography.

PMID- 15507427
TI  - Angiography-induced closure of perimedullary spinal arteriovenous fistula.
AB  - Type 4 spinal vascular malformations are called perimedullary arteriovenous
      fistulae, in which there is a shunt between a radicular artery and intradural
      veins. We report the spinal MR imaging and angiography findings of the
      angiography-induced closure of a type 4 spinal vascular malformation.

PMID- 15507428
TI  - Pulmonary alveolar microlithiasis presenting with crazy-paving pattern on high
      resolution CT.
AB  - Pulmonary alveolar microlithiasis (PAM) is an uncommon chronic disease
      characterized by calcifications within the alveoli and a paucity of symptoms in
      contrast to the imaging findings. We present a 59-year-old woman with a 4-year
      history of shortness of breath on exertion. Lung auscultation revealed random
      wheezes and fine and coarse crackles. Pulmonary function tests showed a
      restrictive pattern. The chest radiograph demonstrated a bilateral symmetric
      micronodular pattern. High resolution CT scan revealed diffuse ground-glass
      attenuation with superimposed septal thickening ("crazy-paving" pattern). The
      patient underwent a lung biopsy, which confirmed the diagnosis of PAM. Our case
      demonstrates that PAM needs to be considerate in the differential diagnosis of
      lung lesions that present with crazy-paving pattern on the high resolution CT.

PMID- 15507429
TI  - Substitutions in region 2.4 of sigma70 allow recognition of the sigmaS-dependent
      aidB promoter.
AB  - The strict dependence of transcription from the aidB promoter (PaidB) on the
      Esigma(S) form of RNA polymerase is because of the presence of a C nucleotide as
      the first residue of the -10 promoter sequence (-12C), which does not allow an
      open complex formation by Esigma(70). In this report, sigma(70) mutants carrying
      either the Q437H or the T440I single amino acid substitutions, which allow -12C
      recognition by sigma(70), were tested for their ability to carry out
      transcription from PaidB. The Gln-437 and Thr-440 residues are located in region
      2.4 of sigma(70) and correspond to Gln-152 and Glu-155 in sigma(S).
      Interestingly, the Q437H mutant of sigma(70), but not T440I, was able to promote
      an open complex formation and to initiate transcription at PaidB. In contrast to
      T440I, a T440E mutant was proficient in carrying out transcription from PaidB. No
      sigma(70) mutant displayed significantly increased interaction with a PaidB
      mutant in which the -12C was substituted by a T (PaidB((C12T))), which is also
      efficiently recognized by wild type sigma(70). The effect of the T440E mutation
      suggests that the corresponding Glu-155 residue in sigma(S) might be involved in 
      12C recognition. However, substitution to alanine of the Glu-155 residue, as well
      as of Gln-152, in the sigma(S) protein did not significantly affect Esigma(S)
      interaction with PaidB. Our results reiterate the importance of the -12C residue
      for sigma(S)-specific promoter recognition and strongly suggest that interaction
      with the -10 sequence and open complex formation are carried out by different
      determinants in the two sigma factors.

PMID- 15507430
TI  - The adenovirus E4orf6 protein inhibits DNA double strand break repair and
      radiosensitizes human tumor cells in an E1B-55K-independent manner.
AB  - The adenoviral protein E4orf6 has been shown to inhibit both in vitro V(D)J
      recombination and adenoviral DNA concatenation, two processes that rely on
      cellular DNA double strand break repair (DSBR) proteins. Most of the known
      activities of E4orf6 during adenoviral infection require its interaction with
      another adenoviral protein, E1B-55K. Here we report that E4orf6, stably expressed
      in RKO human colorectal carcinoma cells or transiently expressed by adenoviral
      vector in U251 human glioblastoma cells, inhibits DSBR and induces significant
      radiosensitization in the absence of E1B-55K. Expression of a mutant form of
      E4orf6 (L245P) failed to radiosensitize RKO cells. E4orf6 reduced DSBR capacity
      in transfected and infected cells, as measured by sublethal DNA damage repair
      assay and phosphorylated H2AX (gamma-H2AX) levels, respectively. Consistent with
      the inhibitory effect of E4orf6 on DSBR, expression of wild-type but not mutant
      E4orf6 reduced recovery of a transfected, replicating reporter plasmid (pSP189)
      in 293 cells but did not increase the mutation frequency measured in the reporter
      plasmid. The kinase activity of DNA-PKcs (the DNA-dependent protein kinase
      catalytic subunit) toward heterologous substrates was not affected by expression
      of E4orf6; however, autophosphorylation of DNA-PKcs at Thr-2609 following
      ionizing radiation was prolonged in the presence of E4orf6 when compared with
      control-infected cells. Our results demonstrate for the first time that E4orf6
      expression hinders the cellular DNA repair process in mammalian cells in the
      absence of E1B-55K or other adenoviral genes and suggest that viral-mediated
      delivery of E4orf6, combined with localized external beam radiation, could be a
      useful approach for the treatment of radioresistant solid tumors such as
      glioblastomas.

PMID- 15507431
TI  - A novel mode of Gleevec binding is revealed by the structure of spleen tyrosine
      kinase.
AB  - Spleen tyrosine kinase (Syk) is a non-receptor tyrosine kinase required for
      signaling from immunoreceptors in various hematopoietic cells. Phosphorylation of
      two tyrosine residues in the activation loop of the Syk kinase catalytic domain
      is necessary for signaling, a phenomenon typical of tyrosine kinase family
      members. Syk in vitro enzyme activity, however, does not depend on
      phosphorylation (activation loop tyrosine --> phenylalanine mutants retain
      catalytic activity). We have determined the x-ray structure of the
      unphosphorylated form of the kinase catalytic domain of Syk. The enzyme adopts a
      conformation of the activation loop typically seen only in activated,
      phosphorylated tyrosine kinases, explaining why Syk does not require
      phosphorylation for activation. We also demonstrate that Gleevec (STI-571,
      Imatinib) inhibits the isolated kinase domains of both unphosphorylated Syk and
      phosphorylated Abl with comparable potency. Gleevec binds Syk in a novel, compact
      cis-conformation that differs dramatically from the binding mode observed with
      unphosphorylated Abl, the more Gleevec-sensitive form of Abl. This finding
      suggests the existence of two distinct Gleevec binding modes: an extended, trans
      conformation characteristic of tight binding to the inactive conformation of a
      protein kinase and a second compact, cis-conformation characteristic of weaker
      binding to the active conformation. Finally, the Syk-bound cis-conformation of
      Gleevec bears a striking resemblance to the rigid structure of the nonspecific,
      natural product kinase inhibitor staurosporine.

PMID- 15507432
TI  - The crystal structure of the herpes simplex virus 1 ssDNA-binding protein
      suggests the structural basis for flexible, cooperative single-stranded DNA
      binding.
AB  - All organisms including animal viruses use specific proteins to bind single
      stranded DNA rapidly in a non-sequence-specific, flexible, and cooperative manner
      during the DNA replication process. The crystal structure of a 60-residue C
      terminal deletion construct of ICP8, the major single-stranded DNA-binding
      protein from herpes simplex virus-1, was determined at 3.0 A resolution. The
      structure reveals a novel fold, consisting of a large N-terminal domain (residues
      9-1038) and a small C-terminal domain (residues 1049-1129). On the basis of the
      structure and the nearest neighbor interactions in the crystal, we have presented
      a model describing the site of single-stranded DNA binding and explaining the
      basis for cooperative binding. This model agrees with the beaded morphology
      observed in electron micrographs.

PMID- 15507433
TI  - Crystal structure of the drug discharge outer membrane protein, OprM, of
      Pseudomonas aeruginosa: dual modes of membrane anchoring and occluded cavity end.
AB  - The OprM lipoprotein of Pseudomonas aeruginosa is a member of the MexAB-OprM
      xenobiotic-antibiotic transporter subunits that is assumed to serve as the drug
      discharge duct across the outer membrane. The channel structure must differ from
      that of the porin-type open pore because the protein facilitates the exit of
      antibiotics but not the entry. For better understanding of the structure-function
      linkage of this important pump subunit, we studied the x-ray crystallographic
      structure of OprM at the 2.56-angstroms resolution. The overall structure
      exhibited trimeric assembly of the OprM monomer that consisted mainly of two
      domains: the membrane-anchoring beta-barrel and the cavity-forming alpha-barrel.
      OprM anchors the outer membrane by two modes of membrane insertions. One is via
      the covalently attached NH(2)-terminal fatty acids and the other is the beta
      barrel structure consensus on the outer membrane-spanning proteins. The beta
      barrel had a pore opening with a diameter of about 6-8 angstroms, which is not
      large enough to accommodate the exit of any antibiotics. The periplasmic alpha
      barrel was about 100 angstroms long formed mainly by a bundle of alpha-helices
      that formed a solvent-filled cavity of about 25,000 angstroms(3). The proximal
      end of the cavity was tightly sealed, thereby not permitting the entry of any
      molecule. The result of this structure was that the resting state of OprM had a
      small outer membrane pore and a tightly closed periplasmic end, which sounds
      plausible because the protein should not allow free access of antibiotics.
      However, these observations raised another unsolved problem about the mechanism
      of opening of the OprM cavity ends. The crystal structure offers possible
      mechanisms of pore opening and pump assembly.

PMID- 15507434
TI  - Sumoylation of MITF and its related family members TFE3 and TFEB.
AB  - MITF and its related family members TFE3 and TFEB heterodimerize with each other,
      recognize the same DNA sequences, and are subject to many of the same post
      translational modifications. We show that lysine residues within conserved small
      ubiquitin-like modifier (SUMO) consensus sites in these family members are
      subject to SUMO modification. Mutation of these sites significantly affects the
      transcriptional activity of MITF but does not alter dimerization, DNA binding,
      stability, or nuclear localization. Mutagenesis reducing the number of MITF
      binding sites in the promoter of TRPM1 from three to one eliminated the
      difference in transcriptional activity between the MITF mutants. Among other MITF
      target gene promoter constructs, differences in transcriptional activity between
      wild type and non-sumoylatable MITF were only seen in promoters with multiple
      MITF binding sites. These data support a synergy control model in which the
      functional consequences of MITF sumoylation depend on promoter context.
      Sumoylation, thus, provides a possible mechanism for altering the effects of MITF
      by affecting the target genes that it activates.

PMID- 15507435
TI  - The N termini of Friend of GATA (FOG) proteins define a novel transcriptional
      repression motif and a superfamily of transcriptional repressors.
AB  - Members of the Friend of GATA (FOG) family of transcriptional co-factors are
      required for the development of both the cardiovascular and hematopoietic
      systems. FOG proteins physically interact with members of the GATA family of
      transcriptional activators and modulate their activity. We have previously shown
      that FOG-2 can bind to the N-terminal zinc finger of GATA4 and, via this
      interaction, repress GATA4-mediated transcriptional activation of various cardiac
      promoters. In this report we further characterize the domain of FOG-2 necessary
      for repression of GATA4 transcriptional activity. We show that FOG-2-mediated
      repression is not blocked by the histone deacetylase inhibitor tricostatin A,
      suggesting that FOG-2 repression of GATA4 occurs via a histone deacetylase
      independent mechanism. N-terminal deletion mutants of FOG-2 revealed that the
      first 12 amino acids of FOG-2 are necessary for FOG-2-mediated repression. Fusion
      of these 12 amino acids to the DNA binding domain of GAL4 demonstrated that this
      region is sufficient to mediate transcriptional repression even when recruited to
      a heterologous promoter. Single amino acid substitutions within this N-terminal
      domain of FOG-2 defined the critical amino acid sequence as RRKQxxPxxI.
      Interestingly, a search of the NCBI protein data base identified several other
      partially characterized zinc finger transcriptional repressors from various
      vertebrate species that contained this motif at their N terminus. Taken together,
      these observations define a novel transcriptional repression motif and a
      superfamily of zinc finger transcriptional repressors.

PMID- 15507436
TI  - The Saccharomyces cerevisiae high mobility group box protein HMO1 contains two
      functional DNA binding domains.
AB  - High mobility group box (HMGB) proteins are architectural proteins whose HMG DNA
      binding domains confer significant preference for distorted DNA, such as 4-way
      junctions. HMO1 is one of 10 Saccharomyces cerevisiae HMGB proteins, and it is
      required for normal growth and plasmid maintenance and for regulating the
      susceptibility of yeast chromatin to nuclease. Using electrophoretic mobility
      shift assays, we have shown here that HMO1 binds 26-bp duplex DNA with K(d) =
      39.6 +/- 5.0 nm and that its divergent box A domain participates in DNA
      interactions, albeit with low affinity. HMO1 has only modest preference for DNA
      with altered conformations, including DNA with nicks, gaps, overhangs, or loops,
      as well as for 4-way junction structures and supercoiled DNA. HMO1 binds 4-way
      junctions with half-maximal saturation of 19.6 +/- 2.2 nm, with only a modest
      increase in affinity in the absence of magnesium ions (half-maximal saturation
      6.1 +/- 1.1 nm). Whereas the box A domain contributes modest structure-specific
      binding, the box B domain is required for high affinity binding. HMO1 bends DNA,
      as measured by DNA cyclization assays, facilitating cyclization of 136-, 105-,
      and 87-bp DNA, but not 75-bp DNA, and it has a significantly longer residence
      time on DNA minicircles compared with linear duplex DNA. The unique DNA binding
      properties of HMO1 are consistent with global roles in the maintenance of
      chromatin structure.

PMID- 15507437
TI  - Mutant copper-zinc superoxide dismutase binds to and destabilizes human low
      molecular weight neurofilament mRNA.
AB  - The mechanism by which mutated copper-zinc superoxide dismutase (SOD1) causes
      familial amyotrophic lateral sclerosis is believed to involve an adverse gain of
      function, independent of the physiological antioxidant enzymatic properties of
      SOD1. In this study, we have observed that mutant SOD1 (G41S, G85A, and G93A) but
      not the wild type significantly reduced the stability of the low molecular weight
      neurofilament mRNA in a dosage-dependent manner. We have also demonstrated that
      mutant SOD1 but not the wild type bound directly to the neurofilament mRNA 3'
      untranslated region and that the binding was necessary to induce mRNA
      destabilization. These observations provide an explanation for a novel gain of
      function in which mutant SOD1 expression in motor neurons alters an intermediate
      filament protein expression.

PMID- 15507438
TI  - Glutathione directly reduces an oxidoreductase in the endoplasmic reticulum of
      mammalian cells.
AB  - The formation of disulfide bonds is an essential step in the folding of many
      glycoproteins and secretory proteins. Non-native disulfide bonds are often formed
      between incorrect cysteine residues, and thus the cell has dedicated a family of
      oxidoreductases that are thought to isomerize non-native bonds. For an
      oxidoreductase to be capable of performing isomerization or reduction reactions,
      it must be maintained in a reduced state. Here we show that most of the
      oxidoreductases are predominantly reduced in vivo. Following oxidative stress the
      oxidoreductases are quickly reduced, demonstrating that a robust reductive
      pathway is in place in mammalian cells. Using ERp57 as a model we show that the
      reductive pathway is cytosol-dependent and that the component responsible for the
      reduction of the oxidoreductases is the low molecular mass thiol glutathione. In
      addition, ERp57 is not reduced following oxidative stress when inhibitors of
      glutathione synthesis or glutathione reduction are added to cells. Glutathione
      directly reduces ERp57 at physiological concentrations in vitro, and biotinylated
      glutathione forms a mixed disulfide with ERp57 in microsomes. Our results
      demonstrate that glutathione plays a direct role in the isomerization of
      disulfide bonds by maintaining the mammalian oxidoreductases in a reduced state.

PMID- 15507439
TI  - Thermodynamic and kinetic analysis of the nitrosyl, carbonyl, and dioxy heme
      complexes of neuronal nitric-oxide synthase. The roles of substrate and
      tetrahydrobiopterin in oxygen activation.
AB  - Mammalian NO synthases catalyze the monooxygenation of L-arginine (L-Arg) to N
      hydroxyarginine (NOHA) and the subsequent monooxygenation of this to NO and
      citrulline. Both steps proceed via formation of an oxyferrous heme complex and
      may ultimately lead to a ferrous NO complex, from which NO must be released.
      Electrochemical reduction of NO-bound neuronal nitricoxide synthase (nNOS)
      oxygenase domain was used to form the ferrous heme NO complex, which was found to
      be stable only in the presence of low NO concentrations, due to catalytic
      degradation of NO at the nNOS heme site. The reduction potential for the heme-NO
      complex was approximately -140 mV, which shifted to 0 mV in the presence of
      either L-Arg or NOHA. This indicates that the complex is stabilized by 14 kJ mol(
      1) in the presence of substrate, consistent with a strong H-bonding interaction
      between NO and the guanidino group. Neither substrate influenced the reduction
      potential of the ferrous heme CO complex, however. Both L-Arg and NOHA appear to
      interact with bound NO in a similar way, indicating that both bind as guanidinium
      ions. The dissociation constant for NO bound to ferrous heme in the presence of l
      Arg was determined electrochemically to be 0.17 nM, and the rate of dissociation
      was estimated to be 10(-4) s(-1), which is much slower than the rate of
      catalysis. Stopped-flow kinetic analysis of oxyferrous formation and decay showed
      that both l-Arg and NOHA also stabilize the ferrous heme dioxy complex, resulting
      in a 100-fold decrease in its rate of decay. Electron transfer from the active
      site cofactor tetrahydrobiopterin (H4B) has been proposed to trigger the
      monoxygenation process. Consistent with this, substitution by the
      analogue/inhibitor 4-amino-H4B stabilized the oxyferrous complex by a further two
      orders of magnitude. H4B is required, therefore, to break down both the
      oxyferrousand ferrous nitrosyl complexes of nNOS during catalysis. The energetics
      of these processes necessitates an electron donor/acceptor operating within a
      specific reduction potential range, defining the role of H4B.

PMID- 15507440
TI  - A unique hydrophobic cluster near the active site contributes to differences in
      borrelidin inhibition among threonyl-tRNA synthetases.
AB  - Borrelidin, a compound with anti-microbial and anti-angiogenic properties, is a
      known inhibitor of bacterial and eukaryal threonyl-tRNA synthetase (ThrRS). The
      inhibition mechanism of borrelidin is not well understood. Archaea contain
      archaeal and bacterial genre ThrRS enzymes that can be distinguished by their
      sequence. We explored species-specific borrelidin inhibition of ThrRSs. The
      activity of ThrRS from Sulfolobus solfataricus and Halobacterium sp. NRC-1 was
      inhibited by borrelidin, whereas ThrRS enzymes from Methanocaldococcus jannaschii
      and Archaeoglobus fulgidus were not. In Escherichia coli ThrRS, borrelidin
      binding induced a conformational change, and threonine was not activated as shown
      by ATP-PP(i) exchange and a transient kinetic assay measuring intrinsic
      tryptophan fluorescence changes. These assays further showed that borrelidin is a
      noncompetitive tight binding inhibitor of E. coli ThrRS with respect to threonine
      and ATP. Genetic selection of borrelidin-resistant mutants showed that borrelidin
      binds to a hydrophobic region (Thr-307, His-309, Cys-334, Pro-335, Leu-489, Leu
      493) proximal to the zinc ion at the active site of the E. coli ThrRS. Mutating
      residue Leu-489 --> Trp reduced the space of the hydrophobic cluster and resulted
      in a 1500-fold increase of the K(i) value from 4 nM to 6 microm. An alignment of
      ThrRS sequences showed that this cluster is conserved in most organisms except
      for some Archaea (e.g. M. jannaschii, A. fulgidus) and some pathogens (e.g.
      Helicobacter pylori). This study illustrates how one class of natural product
      inhibitors affects aminoacyl-tRNA synthetase function, providing potentially
      useful information for structure-based inhibitor design.

PMID- 15507441
TI  - Studies on the N-glycosylation of the subunits of oligosaccharyl transferase in
      Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae, oligosaccharyl transferase (OT) consists of nine
      different subunits. Three of the essential gene products, Ost1p, Wbp1p, and
      Stt3p, are N-linked glycoproteins. To study the function of the N-glycosylation
      of these proteins, we prepared single or multiple N-glycosylation site mutations
      in each of them. We established that the four potential N-glycosylation sites in
      Ost1p and the two potential N-glycosylation sites in Wbp1p were occupied in the
      mature proteins. Interestingly, none of the N-glycosylation sites in these two
      proteins was conserved, and no defect in growth or OT activity was observed when
      the N-glycosylation sites were mutated to block N-glycosylation in either
      subunit. However, in the third glycosylated subunit, Stt3p, there are two
      adjacent potential N-glycosylation sites (N(535)NTWN(539)NT) that, in contrast to
      the other subunits, are highly conserved in eukaryotic organisms. Mass
      spectrometric analysis of a tryptic digest of Stt3p showed that the peptide
      containing the two adjacent N-glycosylation sites was N-glycosylated at one site.
      Furthermore, the glycan chain identified as Man(8)GlcNAc(2) is found linked only
      to Asn(539). Mutation experiments were carried out at these two sites. Four
      single amino acid mutations blocking either N-glycosylation site (N535Q, T537A,
      N539Q, and T541A) resulted in strains that were either lethal or extremely
      temperature sensitive. However, other mutations in the two N-glycosylation sites
      N(535)NTWN(539)NT (N536Q, T537S, N540Q, and T541S), did not exhibit growth
      defects. Based on these studies, we conclude that N-glycosylation of Stt3p at
      Asn(539) is essential for its function in the OT complex.

PMID- 15507442
TI  - The C-terminal residues in the alpha-interacting domain (AID) helix anchor CaV
      beta subunit interaction and modulation of CaV2.3 channels.
AB  - The alpha-interacting domain (AID) in the I-II linker of high voltage-activated
      (HVA) Ca(2+) channel alpha1 subunits binds with high affinity to Ca(V)beta
      auxiliary subunits. The recently solved crystal structures of the AID-Ca(V)beta
      complex in Ca(V)1.1/1.2 have revealed that this interaction occurs through a set
      of six mostly invariant residues Glu/Asp(6), Leu(7), Gly(9), Tyr(10), Trp(13),
      and Ile(14) (where the superscript refers to the position of the residue starting
      with the QQ signature doublet) distributed among three alpha-helical turns in the
      proximal section of the I-II linker. We show herein that alanine mutations of N
      terminal AID residues Gln(1), Gln(2), Ile(3), Glu(4), Glu(6), Leu(7), and Gly(9)
      in Ca(V)2.3 did not abolish [(35)S]Ca(V)beta 1b or [(35)S]Ca(V)beta 3 subunit
      overlay binding to fusion proteins nor did they prevent the typical modulation of
      whole cell currents by Ca(V)beta 3. Mutations of the invariant Tyr(10) with
      either hydrophobic (Ala), aromatic (Phe), or positively charged (Arg, Lys)
      residues yielded Ca(V)beta 3-responsive whole cell currents, whereas mutations
      with negatively charged residues (Asp, Glu) disrupted Ca(V)beta 3 binding and
      modulation. In contrast, modulation and binding by Ca(V)beta 3 was significantly
      weakened in I14A (neutral and hydrophobic) and I14S (neutral and polar) mutants
      and eradicated in negatively charged I14D and I14E or positively charged I14R and
      I14K mutants. Ca(V)beta 3-induced modulation was only preserved with the
      conserved I14L mutation. Molecular replacement analyses carried out using a three
      dimensional homology model of the AID helix from Ca(V)2.3 suggests that a high
      degree of hydrophobicity and a restrained binding pocket could account for the
      strict structural specificity of the interaction site found at position Ile(14).
      Altogether these results indicate that the C-terminal residues Trp(13) (1) and
      Ile(14) anchor Ca(V)beta subunit functional modulation of HVA Ca(2+) channels.

PMID- 15507443
TI  - Cyclophilin C-associated protein is a mediator for fibronectin fragment-induced
      matrix metalloproteinase-13 expression.
AB  - The function of cyclophilin C-associated protein (CyC-AP) on expression of
      extracellular matrix and matrix metalloproteinases (MMPs) was studied in CyC-AP
      null mice. Fibronectin showed increased expression of the 53- and 29-kDa
      fragments in skin and wounds from CyC-AP-null mice. Type I collagen had an
      initial degraded pattern in the skin of CyC-AP-null mice, which did not occur in
      wild-type mice. MMP-3, MMP-13, MMP-14, and tumor necrosis factor-alpha (TNFalpha)
      had a higher expression in CyC-AP-null skin. During wound healing, MMP-13 and
      TNFalpha were stimulated to an even higher level, suggesting they are regulated
      by multiple factors. To understand the regulatory mechanisms of the up-regulated
      MMPs, the direct effects of TNFalpha, IL-1beta, 45-kDa fibronectin fragment (FN
      45), and the 70-kDa fibronectin fragments (FN-70) on the expression of MMPs were
      studied. MMP-13 expression increased significantly in both CyC-AP-null and wild
      type dermal fibroblasts after treatment with IL-1beta or with TNFalpha. However,
      MMP-13 expression did not increase in CyC-AP-null fibroblasts but did increase
      only in wild-type fibroblasts after FN-45 and FN-70 treatment. MMP-3 activation
      was induced by FN-45 and did not show a difference between CyC-AP-null and wild
      type fibroblasts, suggesting different regulatory pathways for FN-45 on MMP-13
      and MMP-3 expression. Our data are the first to demonstrate that deletion of CyC
      AP can abolish fibronectin fragment-induced MMP-13 expression through an unknown
      mechanism. CyC-AP is an important factor for the regulation of MMP-13 expression.

PMID- 15507444
TI  - A role for Pet100p in the assembly of yeast cytochrome c oxidase: interaction
      with a subassembly that accumulates in a pet100 mutant.
AB  - The biogenesis of multimeric protein complexes of the inner mitochondrial
      membrane in yeast requires a number of nuclear-coded ancillary proteins. One of
      these, Pet100p, is required for cytochrome c oxidase. Previous studies have shown
      that Pet100p is not required for the synthesis, processing, or targeting of
      cytochrome c oxidase subunits to the mitochondrion nor for heme A biosynthesis.
      Here, we report that Pet100p does not affect the localization of cytochrome c
      oxidase subunit polypeptides to the inner mitochondrial membrane but instead
      functions after they have arrived at the inner membrane. We have also localized
      Pet100p to the inner mitochondrial membrane in wild type cells, where it is
      present in a subassembly (Complex A) with cytochrome c oxidase subunits VII,
      VIIa, and VIII. Pet100p does not interact with the same subunits after they have
      been assembled into the holoenzyme. In addition, we have identified two
      subassemblies that are present in pet100 null mutant cells: one subassembly
      (Complex A') is composed of subunits VII, VIIa, and VIII but not Pet100p, and
      another subassembly (Complex B) is composed of subunits Va and VI. Because pet100
      null mutant cells lack assembled cytochrome c oxidase but accumulate Complexes A'
      and B it appears likely that these subassemblies of cytochrome c oxidase subunits
      are intermediates along an assembly pathway for holocytochrome c oxidase and that
      Pet100p functions in this pathway to facilitate the interaction(s) between
      Complex A' and other cytochrome c oxidase subassemblies and subunits.

PMID- 15507445
TI  - Nidovirus sialate-O-acetylesterases: evolution and substrate specificity of
      coronaviral and toroviral receptor-destroying enzymes.
AB  - Many viruses achieve reversible attachment to sialic acid (Sia) by encoding
      envelope glycoproteins with receptor-binding and receptor-destroying activities.
      Toroviruses and group 2 coronaviruses bind to O-acetylated Sias, presumably via
      their spike proteins (S), whereas other glycoproteins, the hemagglutinin
      esterases (HE), destroy Sia receptors by de-O-acetylation. Here, we present a
      comprehensive study of these enzymes. Sialate-9-O-acetylesterases specific for 5
      N-acetyl-9-O-acetylneuraminic acid, described for bovine and human coronaviruses,
      also occur in equine coronaviruses and in porcine toroviruses. Bovine
      toroviruses, however, express novel sialate-9-O-acetylesterases, which prefer the
      di-O-acetylated substrate 5-N-acetyl-7(8),9-di-O-acetylneuraminic acid. Whereas
      most rodent coronaviruses express sialate-4-O-acetylesterases, the HE of murine
      coronavirus DVIM cleaves 9-O-acetylated Sias. Under the premise that HE
      specificity reflects receptor usage, we propose that two types of Sias serve as
      initial attachment factors for coronaviruses in mice. There are striking
      parallels between orthomyxo- and nidovirus biology. Reminiscent of antigenic
      shifts in orthomyxoviruses, rodent coronaviruses exchanged S and HE sequences
      through recombination to extents not appreciated before. As for orthomyxovirus
      reassortants, the fitness of nidovirus recombinant offspring probably depends
      both on antigenic properties and on compatibility of receptor-binding and
      receptor-destroying activities.

PMID- 15507446
TI  - Identification of human hornerin and its expression in regenerating and psoriatic
      skin.
AB  - We previously isolated a new member of the fused-type S100 protein family
      (hornerin) from the mouse (Makino, T., Takaishi, M., Morohashi, M., and Huh, N.
      h. (2001) J. Biol. Chem. 276, 47445-47452). Mouse hornerin shares structural
      features, expression profiles, and intracellular localization with profilaggrin,
      indicating possible involvement of hornerin in cornification. In this study, we
      identified and partially characterized a human ortholog of mouse hornerin. The
      human hornerin gene was mapped between trichohyalin and filaggrin on chromosome
      1q21.3, the region being completely syntenic with the counterpart of the mouse.
      The deduced amino acid sequence of 2850 residues shows typical structural
      features of "fused-type" S100 protein family members. Mature transcripts and
      protein from human hornerin were not detected in normal stratified epithelium,
      including the trunk epidermis, tongue, and esophagus. After screening of various
      normal and pathological human tissues, we found that human hornerin was expressed
      in psoriatic skin. Hornerin protein was present in the keratinizing region,
      although at a lower level and in fewer cells compared with filaggrin. Mature
      transcripts and protein from hornerin were also detected in regenerating human
      skin after wounding. Hornerin mRNA was induced 5 days after wounding. The mRNA
      level remained almost constant until 15 days and declined at 30 days after
      wounding. Hornerin protein was detected in the proximal epidermis (but not in the
      distal epidermis) at 15 days after wounding. These results indicate that hornerin
      has a function similar to but distinct from that of filaggrin in cornification.

PMID- 15507447
TI  - Role of the Sc C terminus in transcriptional activation and E(spl) repressor
      recruitment.
AB  - Neurogenesis in all animals is triggered by the activity of a group of basic
      helix-loop-helix transcription factors, the proneural proteins, whose expression
      endows ectodermal regions with neural potential. The eventual commitment to a
      neural precursor fate involves the interplay of these proneural transcriptional
      activators with a number of other transcription factors that fine tune
      transcriptional responses at target genes. Most prominent among the factors
      antagonizing proneural protein activity are the HES basic helix-loop-helix
      proteins. We have previously shown that two HES proteins of Drosophila,
      E(spl)mgamma and E(spl)m7, interact with the proneural protein Sc and thereby get
      recruited onto Sc target genes to repress transcription. Using in vivo and in
      vitro assays we have now discovered an important dual role for the Sc C-terminal
      domain. On one hand it acts as a transcription activation domain, and on the
      other it is used to recruit E(spl) proteins. In vivo, the Sc C-terminal domain is
      required for E(spl) recruitment in an enhancer context-dependent fashion,
      suggesting that in some enhancers alternative interaction surfaces can be used to
      recruit E(spl) proteins.

PMID- 15507448
TI  - ADAM10 mediates ectodomain shedding of the betacellulin precursor activated by p
      aminophenylmercuric acetate and extracellular calcium influx.
AB  - Betacellulin belongs to the family of epidermal growth factor-like growth factors
      that are expressed as transmembrane precursors and undergo proteolytic ectodomain
      shedding to release a soluble mature growth factor. In this study, we
      investigated the ectodomain shedding of the betacellulin precursor (pro-BTC) in
      conditionally immortalized wild-type (WT) and ADAM-deficient cell lines.
      Sequential ectodomain cleavage of the predominant cell-surface 40-kDa form of pro
      BTC generated a major (26-28 kDa) and two minor (20 and 15 kDa) soluble forms and
      a cellular remnant lacking the ectodomain (12 kDa). Pro-BTC shedding was
      activated by calcium ionophore (A23187) and by the metalloprotease activator p
      aminophenylmercuric acetate (APMA), but not by phorbol esters. Culturing cells in
      calcium-free medium or with the protein kinase Cdelta inhibitor rottlerin, but
      not with broad-based protein kinase C inhibitors, blocked A23187-activated pro
      BTC shedding. These same treatments were without effect for constitutive and APMA
      induced cleavage events. All pro-BTC shedding was blocked by treatment with a
      broad-spectrum metalloprotease inhibitor (GM6001). In addition, constitutive and
      activated pro-BTC shedding was differentially blocked by TIMP-1 or TIMP-3, but
      was insensitive to treatment with TIMP-2. Pro-BTC shedding was functional in
      cells from ADAM17- and ADAM9-deficient mice and in cells overexpressing WT or
      catalytically inactive ADAM17. In contrast, overexpression of WT ADAM10 enhanced
      constitutive and activated shedding of pro-BTC, whereas overexpression of
      catalytically inactive ADAM10 reduced shedding. These results demonstrate, for
      the first time, activated pro-BTC shedding in response to extracellular calcium
      influx and APMA and provide evidence that ADAM10 mediates constitutive and
      activated pro-BTC shedding.

PMID- 15507449
TI  - E2A-PBX1 interacts directly with the KIX domain of CBP/p300 in the induction of
      proliferation in primary hematopoietic cells.
AB  - The E2A gene encodes DNA-binding transcription factors, called E12 and E47,
      involved in cell specification and maturation. E2A is also involved in a
      chromosomal translocation that leads to the expression of an oncogenic
      transcription factor called E2A-PBX1 in cases of acute leukemia. In the work
      described here, we elucidate the interaction between E2A-PBX1 and transcriptional
      co-activators. We confirm that the E2A portion can interact with CBP and PCAF and
      map required elements on E2A and CBP. On CBP, the interaction involves the KIX
      domain, a well characterized domain that mediates interactions with several other
      oncogenic transcription factors. On E2A, the interaction with CBP requires
      conserved alpha-helical domains that reside within activation domains 1 and 2
      (AD1 and AD2, respectively). Using purified, recombinant proteins, we show that
      the E2A-CBP interaction is direct. Notwithstanding the previously demonstrated
      ability of AD1 and AD2 to function independently, some of our findings suggest
      functional cooperativity between these two domains. Finally, we show that the
      CBP/p300-interactive helical domains of E2A are important in the induction of
      proliferation in cultured primary bone marrow cells retrovirally transduced with
      E2A-PBX1. Our findings suggest that some aspects of E2A-PBX1 oncogenesis involve
      a direct interaction with the KIX domain of CBP/p300.

PMID- 15507450
TI  - Myocardial ischemia differentially regulates LKB1 and an alternate 5'-AMP
      activated protein kinase kinase.
AB  - During myocardial ischemia, activation of 5'-AMP-activated protein kinase (AMPK)
      leads to the stimulation of glycolysis and fatty acid oxidation. Together these
      metabolic changes contribute to cardiac dysfunction. Although AMPK signaling in
      the ischemic heart is well characterized, the relative contribution of
      phosphorylation by AMPK kinase (AMPKK), and positive allosterism by the ratios of
      AMP:ATP and creatine (Cr):phosphocreatine (PCr), in stimulating AMPK during
      ischemia are unknown. In hearts subjected to severe ischemia, the ratios of
      AMP:ATP and Cr:PCr were significantly elevated as compared with aerobic hearts.
      Severe ischemia stimulated AMPK signaling, as demonstrated by an increase in both
      AMPK activity and acetyl-CoA carboxylase phosphorylation. Although AMPK
      phosphorylation was increased by severe ischemia, the protein abundance and
      activity of the recently identified AMPKK, LKB1, were similar between aerobic and
      severely ischemic hearts. However, in contrast to LKB1, the activity of AMPKK was
      stimulated in severely ischemic hearts. To further delineate the relative roles
      of positive allosterism and AMPKK in the regulation of AMPK during ischemia,
      hearts were subjected to mild ischemia. Although mild ischemia did not alter the
      ratios of AMP:ATP and Cr:PCr, mild ischemia increased AMPK activity and increased
      AMPK phosphorylation. Mild ischemia also stimulated the activity of AMPKK. In
      summary, we demonstrate that myocardial ischemia stimulates AMPK via an AMPKK
      other than LKB1. Additionally, we show that changes in high energy phosphates are
      not essential for the activation of AMPK by ischemia. Our data emphasize the
      critical role AMPKK plays in mediating AMPK signaling during myocardial ischemia.

PMID- 15507451
TI  - The membrane-associated inhibitor of apoptosis protein, BRUCE/Apollon,
      antagonizes both the precursor and mature forms of Smac and caspase-9.
AB  - Smac/DIABLO, HtrA2/Omi, and caspase-9 play key roles in the initiation of
      apoptosis. The inhibitor of apoptosis proteins (IAPs) are believed to bind to the
      N-terminal IAP binding motifs of the mature (proteolytically processed) forms of
      Smac, HtrA2, and caspase-9. However, we show here that BRUCE/Apollon, a 528-kDa
      IAP whose degradation promotes apoptosis, associates with their precursors as
      well as the mature forms by binding to regions in addition to the IAP binding
      motif. Through these associations, BRUCE promotes the degradation of Smac and
      inhibits the activity of caspase-9 but not the effector caspase, caspase-3. In
      response to apoptotic stimuli, BRUCE is degraded by proteasomes and/or cleaved by
      caspases and HtrA2 depending on the specific stimulus and the cell type. These
      results suggest that the ability of BRUCE to antagonize both the precursor and
      mature forms of Smac and caspase-9 is an important mechanism for the prevention
      of apoptosis under normal conditions.

PMID- 15507452
TI  - Conformational HER-2/neu B-cell epitope peptide vaccine designed to incorporate
      two native disulfide bonds enhances tumor cell binding and antitumor activities.
AB  - Cancer vaccines designed to elicit an antibody response that target antigenic
      sites on a tumor antigen must closely mimic the three-dimensional structure of
      the corresponding region on the antigen. We have designed a complex immunogen
      derived from the extracellular domain of human HER-2/neu-(626-649) that
      represents a three-dimensional epitope. We have successfully introduced two
      disulfide bonds into this sequence, thereby recapitulating the natural disulfide
      pairings observed in the native protein. To evaluate the immunogenicity of the
      doubly cyclized disulfide-linked peptide versus the free uncyclized peptide we
      examined the induction of antibody responses in both inbred and outbred mice
      strains, with both constructs eliciting high titered antibodies. The disulfide
      paired specific antibodies exhibited enhanced cross-reactivity to HER-2/neu
      expressed on BT-474 cell line as determined by flow cytometry. The antitumor
      activities of the disulfidepaired specific antibodies did not improve the in
      vitro growth inhibition of human breast cancer cells overexpressing HER-2, but
      showed superior antitumor responses in the context of ADCC and interferon-gamma
      induction. Inbred mice (FVB/n) vaccinated with the disulfide-paired epitope
      exhibited a statistically significant reduction in the development of exogenously
      administered tumors in vivo compared with mice receiving either the free
      uncyclized or the promiscuous T-cell epitope (MVF) control peptide (p = 0.001).
      This study demonstrates the feasibility and importance of designing
      conformational epitopes that mimic the tertiary structure of the native protein
      for eliciting biologically relevant anti-tumor antibodies. Such approaches are a
      prerequisite to the design of effective peptide vaccines.

PMID- 15507453
TI  - Identification of a region of fast skeletal troponin T required for stabilization
      of the coiled-coil formation with troponin I.
AB  - We have previously identified evolutionarily conserved heptad hydrophobic repeat
      (HR) domains in all isoprotein members of troponin T (TnT) and troponin I (TnI),
      two subunits of the Ca(2+)-regulatory troponin complex. Our suggestion that the
      HR domains are involved in the formation of a coiled-coil heterodimer of TnT and
      TnI has been recently confirmed by the crystal structure of the core domain of
      the human cardiac troponin complex. Here we studied a series of recombinant
      deletion mutants of the fast skeletal TnT to determine the minimal sequence
      required for stable coiled-coil formation with the HR domain of the fast skeletal
      TnI. Using circular dichroism spectroscopy, we measured the alpha helical content
      of the coiled-coil formed by the various TnT peptides with TnI HR domain.
      Sedimentation equilibrium experiments confirmed that the individual peptides of
      TnT were monomeric but formed heterodimers when mixed with HR domain of TnI.
      Isothermal titration calorimetry was then used to directly measure the affinity
      of the TnT peptides for the TnI HR domain. Surprisingly we found that the HR
      regions alone of the fast skeletal TnT and TnI, as defined earlier, were
      insufficient to form a coiled-coil. Furthermore we showed that an additional 14
      amino acid residues N-terminal to the conserved HR region (TnT residues 165-178)
      are essential for the stable coiled-coil formation. We discuss the implication of
      our finding in the fast skeletal troponin isoform in the light of the crystal
      structure of the cardiac isoform.

PMID- 15507454
TI  - In vivo and in vitro analysis of cardiac troponin I phosphorylation.
AB  - Adrenergic stimulation induces positive changes in cardiac contractility and
      relaxation. Cardiac troponin I is phosphorylated at different sites by protein
      kinase A and protein kinase C, but the effects of these post-translational
      modifications on the rate and extent of contractility and relaxation during beta
      adrenergic stimulation in the intact animal remain obscure. To investigate the
      effect(s) of complete and chronic cTnI phosphorylation on cardiac function, we
      generated transgenic animals in which the five possible phosphorylation sites
      were replaced with aspartic acid, mimicking a constant state of complete
      phosphorylation (cTnI-AllP). We hypothesized that chronic and complete
      phosphorylation of cTnI might result in increased morbidity or mortality, but
      complete replacement with the transgenic protein was benign with no detectable
      pathology. To differentiate the effects of the different phosphorylation sites,
      we generated another mouse model, cTnI-PP, in which only the protein kinase A
      phosphorylation sites (Ser(23)/Ser(24)) were mutated to aspartic acid. In
      contrast to the cTnIAllP, the cTnI-PP mice showed enhanced diastolic function
      under basal conditions. The cTnI-PP animals also showed augmented relaxation and
      contraction at higher heart rates compared with the nontransgenic controls.
      Nuclear magnetic resonance amide proton/nitrogen chemical shift analysis of
      cardiac troponin C showed that, in the presence of cTnI-AllP and cTnI-PP, the N
      terminus exhibits a more closed conformation, respectively. The data show that
      protein kinase C phosphorylation of cTnI plays a dominant role in depressing
      contractility and exerts an antithetic role on the ability of protein kinase A to
      increase relaxation.

PMID- 15507455
TI  - A differentiation-dependent splice variant of myosin light chain kinase, MLCK1,
      regulates epithelial tight junction permeability.
AB  - Activation of Na(+)-nutrient cotransport leads to increased tight junction
      permeability in intestinal absorptive (villus) enterocytes. This regulation
      requires myosin II regulatory light chain (MLC) phosphorylation mediated by MLC
      kinase (MLCK). We examined the spatiotemporal segregation of MLCK isoform
      function and expression along the crypt-villus axis and found that long MLCK,
      which is expressed as two alternatively spliced isoforms, accounts for 97 +/- 4%
      of MLC kinase activity in interphase intestinal epithelial cells. Expression of
      the MLCK1 isoform is limited to well differentiated enterocytes, both in vitro
      and in vivo, and this expression correlates closely with development of Na(+)
      nutrient cotransport-dependent tight junction regulation. Consistent with this
      role, MLCK1 is localized to the perijunctional actomyosin ring. Furthermore,
      specific knockdown of MLCK1 using siRNA reduced tight junction permeability in
      monolayers with active Na(+)-glucose cotransport, confirming a functional role
      for MLCK1. These results demonstrate unique physiologically relevant patterns of
      expression and subcellular localization for long MLCK isoforms and show that
      MLCK1 is the isoform responsible for tight junction regulation in absorptive
      enterocytes.

PMID- 15507456
TI  - Severe acute respiratory syndrome coronavirus 3C-like proteinase N terminus is
      indispensable for proteolytic activity but not for enzyme dimerization.
      Biochemical and thermodynamic investigation in conjunction with molecular
      dynamics simulations.
AB  - Severe acute respiratory syndrome (SARS) coronavirus is a novel human coronavirus
      and is responsible for SARS infection. SARS coronavirus 3C-like proteinase (SARS
      3CL(pro)) plays key roles in viral replication and transcription and is an
      attractive target for anti-SARS drug discovery. In this report, we quantitatively
      characterized the dimerization features of the full-length and N-terminal
      residues 1-7 deleted SARS 3CL(pro)s by using glutaraldehyde cross-linking SDS
      PAGE, size-exclusion chromatography, and isothermal titration calorimeter
      techniques. Glutaraldehyde cross-linking SDS-PAGE and size-exclusion
      chromatography results show that, similar to the full-length SARS 3CL(pro), the N
      terminal deleted SARS 3CL(pro) still remains a dimer/monomer mixture within a
      wide range of protein concentrations. Isothermal titration calorimeter
      determinations indicate that the equilibrium dissociation constant (K(d)) of the
      N-terminal deleted proteinase dimer (262 microm) is very similar to that of the
      full-length proteinase dimer (227 microm). Enzymatic activity assay using the
      fluorescence resonance energy transfer method reveals that N-terminal deletion
      results in almost complete loss of enzymatic activity for SARS 3CL(pro).
      Molecular dynamics and docking simulations demonstrate the N-terminal deleted
      proteinase dimer adopts a state different from that of the full-length proteinase
      dimer, which increases the angle between the two protomers and reduces the
      binding pocket that is not beneficial to the substrate binding. This conclusion
      is verified by the surface plasmon resonance biosensor determination, indicating
      that the model substrate cannot bind to the N-terminal deleted proteinase. These
      results suggest the N terminus is not indispensable for the proteinase
      dimerization but may fix the dimer at the active state and is therefore vital to
      enzymatic activity.

PMID- 15507457
TI  - Peroxiredoxin-linked detoxification of hydroperoxides in Toxoplasma gondii.
AB  - The apicomplexan parasite Toxoplasma gondii is highly susceptible to oxidative
      stress caused by tert-butyl-hydroperoxide, juglone, and phenazine methylsulfate
      with IC(50) in the nanomolar range. Using dichlorofluorescein diacetate, a
      detector of endogenous oxidative stress, it was shown that juglone and phenazine
      methylsulfate are potentially toxic to the parasites without affecting the host
      cells. These results demonstrate that T. gondii is vulnerable to oxidative
      challenge that results from disruption of its redox balance and so this could be
      an effective approach to therapeutic intervention. This study has characterized
      redox active and antioxidant peroxidases belonging to the class of 1-Cys and 2
      Cys peroxiredoxins that play crucial roles in maintaining redox balance. The
      tachyzoite stages of T. gondii express thioredoxin (TgTrx), 1-Cys peroxiredoxin
      (TgTrx-Px2), and a 2-Cys peroxiredoxin (TgTrx-Px1) and immunofluorescent studies
      revealed that all three proteins are located in the cytosol of the parasite
      confirming previous studies on TgTrx-Px1 (Kwok, L.Y., Schluter, D., Clayton, C.,
      and Soldati, D. (2004) Mol. Microbiol. 51, 47-61). TgTrx-Px1 showed K(m) values
      for H(2)O(2) and tert-butyl hydroperoxide in the nanomolar range, emphasizing the
      great affinity of the protein for theses substrates. Moreover, the catalytic
      efficiency of TgTrx-Px1 for these substrates at 10(6)-10(7) M(-1) s(-1) is
      unusually high, which qualifies the enzyme as an extremely potent antioxidant.
      Kinetic analyses revealed that TgTrx-Px1 is inhibited by tert-butyl
      hydroperoxide, and apparent inhibition constants were determined to be between 33
      and 35.6 microm depending on the concentration of the non-inhibitory substrate
      thioredoxin. TgTrx-Px2 protected glutamine synthetase from inactivation by
      Fe(3+)/DTT, showing that it is an active peroxiredoxin.

PMID- 15507458
TI  - A comparative proteomic strategy for subcellular proteome research: ICAT approach
      coupled with bioinformatics prediction to ascertain rat liver mitochondrial
      proteins and indication of mitochondrial localization for catalase.
AB  - Subcellular proteomics, as an important step to functional proteomics, has been a
      focus in proteomic research. However, the co-purification of "contaminating"
      proteins has been the major problem in all the subcellular proteomic research
      including all kinds of mitochondrial proteome research. It is often difficult to
      conclude whether these "contaminants" represent true endogenous partners or
      artificial associations induced by cell disruption or incomplete purification. To
      solve such a problem, we applied a high-throughput comparative proteome
      experimental strategy, ICAT approach performed with two-dimensional LC-MS/MS
      analysis, coupled with combinational usage of different bioinformatics tools, to
      study the proteome of rat liver mitochondria prepared with traditional
      centrifugation (CM) or further purified with a Nycodenz gradient (PM). A total of
      169 proteins were identified and quantified convincingly in the ICAT analysis, in
      which 90 proteins have an ICAT ratio of PM:CM>1.0, while another 79 proteins have
      an ICAT ratio of PM:CM<1.0. Almost all the proteins annotated as mitochondrial
      according to Swiss-Prot annotation, bioinformatics prediction, and literature
      reports have a ratio of PM:CM>1.0, while proteins annotated as extracellular or
      secreted, cytoplasmic, endoplasmic reticulum, ribosomal, and so on have a ratio
      of PM:CM<1.0. Catalase and AP endonuclease 1, which have been known as
      peroxisomal and nuclear, respectively, have shown a ratio of PM:CM>1.0,
      confirming the reports about their mitochondrial location. Moreover, the 125
      proteins with subcellular location annotation have been used as a testing dataset
      to evaluate the efficiency for ascertaining mitochondrial proteins by ICAT
      analysis and the bioinformatics tools such as PSORT, TargetP, SubLoc, MitoProt,
      and Predotar. The results indicated that ICAT analysis coupled with combinational
      usage of different bioinformatics tools could effectively ascertain mitochondrial
      proteins and distinguish contaminant proteins and even multilocation proteins.
      Using such a strategy, many novel proteins, known proteins without subcellular
      location annotation, and even known proteins that have been annotated as other
      locations have been strongly indicated for their mitochondrial location.

PMID- 15507459
TI  - Principal component analysis is a powerful instrument in occupational hygiene
      inquiries.
AB  - Several investigators have successfully used principal component analysis (PCA)
      in interpreting occupational hygiene data. However, traditional textbooks in
      occupational hygiene provide no guidance for the application and interpretation
      of PCA. In this article I briefly review the basics of PCA (for those not
      statistically inclined), provide some guidelines for performing PCA (and
      designing studies that use the power of PCA), illustrate its application in
      understanding exposure to mixtures and the characterization of 'peak exposure',
      and highlight other benefits that occupational hygienists stand to gain by
      including PCA in their 'statistical toolkit'. I hope that this article will
      promote greater use and understanding of a data analysis approach that has long
      been helping investigators outside the field of occupational hygiene to unravel
      the structure behind the complex relationships among multiple correlated
      variables.

PMID- 15507460
TI  - Evaluation of exposure and health care worker response to nebulized
      administration of tgAAVCF to patients with cystic fibrosis.
AB  - A study was conducted to assess health care worker exposure to tgAAVCF during the
      aerosolized administration of this experimental gene transfer agent in clinical
      trials for the treatment of cystic fibrosis (CF). tgAAVCF is a recombinant adeno
      associated virus (AAV) genetically engineered to contain the human CF
      transmembrane conductance regulator cDNA. Study subjects included eight health
      care workers involved in the administration of tgAAVCF in a phase II study and 12
      control health care workers who were involved with the treatment of CF patients,
      but not administration of the study drug. The exposure assessment entailed the
      determination of personal and area airborne tgAAVCF concentrations. In addition,
      serologic status of the health care workers was evaluated throughout the study
      for the presence of antibodies to AAV. A symptom survey was also completed by
      both the active and control health care workers. Air samples were analyzed by an
      infectivity assay (active vector) and a DNA polymerase chain reaction
      amplification procedure (vector DNA). Air monitoring was conducted during 13
      tgAAVCF and seven placebo administrations. Active vector and vector particles
      were detected in four of 51 and 48 of 51 air samples collected during the
      administration of tgAAVCF, respectively. Based on the airborne vector particle
      concentration, the workers' exposure was estimated to be 0.0006% of the
      administered dose. At this level of exposure, the prevalence of symptoms was very
      low, the spectrum was similar in both study groups and did not result in any
      reported negative health effects.

PMID- 15507462
TI  - A spoonful of sugar helps the medicine go down...

PMID- 15507463
TI  - Social research on the under-16s: a consideration of the issues from a UK
      perspective.
AB  - This article aims to consider the current situation with regard to the issue of
      consent in relation to health-based research on the under-16s. It considers the
      legal situation with regard to the issues of consent, assent and dissent, and
      their application to research. Although under-16s can consent to treatment if
      deemed competent according to the 'Fraser guidelines', application of this
      principle in relation to research appears to be less clear with variability in
      published guidance and the approach taken by ethics committees. Recent policy
      changes including Research Governance have increased the scrutiny of consent to
      research, and current changes appear likely to increase the requirement for
      parental consent for those aged below 18 years. The impact of these ambiguities
      and changes upon young people as service users are considered with particular
      reference to sexual health, where they often access the service as autonomous
      individuals.

PMID- 15507464
TI  - Pain assessment tools: children's nurses' views.
AB  - The persistence of inadequate treatment of pain in children could be due to lack
      of knowledge and nurses' failure to assess and manage pain effectively. It is
      recognized that effective pain assessment leads to more satisfied children and
      families. This study explored children's nurses' views on the use of pain
      assessment tools in a tertiary referral centre. Almost two-thirds of nurses did
      not have a preference for a pain assessment tool, but nearly three-quarters of
      nurses surveyed agreed that the introduction of pain assessment tools would
      improve documentation. When nurses were asked how much time they needed for
      education on these tools, 83 percent wanted only two hours, although almost half
      stated lack of knowledge or education as the main obstacle to use of a pain
      assessment tool. The inconsistencies in these replies could reflect the
      conflicting demands between the nurses' need to increase their knowledge of pain
      assessment while managing a heavy workload.

PMID- 15507465
TI  - Perceived vulnerability: a comparison of parents and children.
AB  - This study examined the agreement between parents' and children's perceptions of
      children's vulnerability to illness. While extreme perceptions of vulnerability,
      such as vulnerable child syndrome, are described as disorders of the parent-child
      relationship, children's health-related cognitions have not been examined as part
      of this process. The self-perceptions of health of 47 pre-school-aged children
      and their parents were evaluated through an interview and a survey respectively.
      Risk factors for vulnerable child syndrome predicted elevated perceptions of
      vulnerability for parents but not for children. Agreement on the child's level of
      vulnerability to illness was high, except that only one-third of the children
      whose parents classified them as more vulnerable relative to their peers
      classified themselves in this way. The results suggest that children's
      perceptions of their health status should be incorporated into therapeutic work
      with families in which children are perceived as medically vulnerable.

PMID- 15507466
TI  - Smoking among parents of pediatric cancer patients and children's exposure to
      environmental tobacco smoke.
AB  - For 303 children newly diagnosed with cancer, we investigated the prevalence of
      parental smoking and examined patients' respiratory or pulmonary symptoms
      according to household smoking status. Results indicated that approximately 45
      percent of patients came from households with at least one current parent smoker
      and 20 percent of current non-smoking parents reported past tobacco use. There
      was a trend for more patients from smoking households to experience respiratory
      problems than patients from non-smoking households (p = .068). In conclusion,
      many patients are at risk for parental smoke exposure and associated health
      problems if they are continually exposed during therapy. Clinician-delivered
      interventions to reduce environmental smoke exposure are clearly warranted.

PMID- 15507467
TI  - Young people's experience of emergency medical services as road traffic accident
      victims: a pilot qualitative study.
AB  - A visit to the Accident and Emergency (A&E) department following an accident is
      often a young person's first experience of hospital. A&E is a pressured
      environment which can be frightening and stressful for young people. This study
      reports the views of young people who have had contact with emergency medical
      services following a road traffic accident (RTA). Negative experiences were
      volunteered more than positive experiences. Concerns were reported around being
      physically restricted, receiving inadequate information, feeling that they were
      not understood, experiencing physical discomforts and feeling lonely. This
      article highlights the need to provide adequately for the younger A&E patient by
      supplying information, communicating appropriately and offering an environment
      that is more appropriate for young people.

PMID- 15507470
TI  - Turning on stem cell cardiogenesis with extremely low frequency magnetic fields.
AB  - Modulation of stem cell differentiation is an important assignment for cellular
      engineering. Embryonic stem (ES) cells can differentiate into cardiomyocytes, but
      the efficiency is typically low. Here, we show that exposure of mouse ES cells to
      extremely low frequency magnetic fields triggered the expression of GATA-4 and
      Nkx-2.5, acting as cardiac lineage-promoting genes in different animal species,
      including humans. Magnetic fields also enhanced prodynorphin gene expression, and
      the synthesis and secretion of dynorphin B, an endorphin playing a major role in
      cardiogenesis. These effects occurred at the transcriptional level and ultimately
      ensued into a remarkable increase in the yield of ES-derived cardiomyocytes.
      These results demonstrate the potential use of magnetic fields for modifying the
      gene program of cardiac differentiation in ES cells without the aid of gene
      transfer technologies and may pave the way for novel approaches in tissue
      engineering and cell therapy.

PMID- 15507471
TI  - The proinvasive activity of Wnt-2 is mediated through a noncanonical Wnt pathway
      coupled to GSK-3beta and c-Jun/AP-1 signaling.
AB  - Inappropriate activation of the Wnt/APC/beta-catenin signaling pathways plays a
      critical role at early stages in a variety of human cancers. However, their
      respective implication in tumor cell invasion is still hypothetical. Here, we
      show that two activators of the canonical Wnt/beta-catenin transcription pathway,
      namely Dvl-2, the Axin 501-560 fragment binding glycogen synthase kinase -3beta
      (GSK-3beta), and the negative Wnt regulator wt-Axin did not alter cell invasion
      into type I collagen. In addition, both Dvl-2 and Axin 501-560 exerted a
      permissive action on the proinvasive activity of HGF and intestinal trefoil
      factor. Upstream activation of Wnt signaling by the Wnt-2 and Wnt-3a ligands,
      stable overexpression of Wnt-2, as well as GSK-3beta inhibition by lithium,
      SB216763, and GSK-3beta dominant negative forms (K85R and R96E) conferred the
      invasive phenotype through several proinvasive pathways. Induction of the matrix
      metalloprotease MMP-7 (matrilysin) gene and protein by Wnt-2 was abolished by
      inactivation of the AP-1 binding site in the promoter. Accordingly, invasion
      induced by Wnt-2 was prevented by soluble FRP-3 and FRP-1, sequestration of
      Gbetagamma subunits, depletion of the GSK-3beta protein by RNA interference, the
      c-Jun dominant negative mutant TAM67 and was not reversed by wt-Axin. Thus, the
      proinvasive activity of Wnt-2 is mediated by a noncanonical Wnt pathway using GSK
      3beta and the AP-1 oncogene. Our data provide a potential clue for our
      understanding of the action and crosstalk between Wnt activators and other
      proinvasive pathways, in relation with matrix substrates and proteases in human
      cancers.

PMID- 15507472
TI  - Formyl-peptide receptor is not involved in the protection afforded by annexin 1
      in murine acute myocardial infarct.
AB  - Recent interest in the annexin 1 field has come from the notion that specific G
      protein-coupled receptors, members of the formyl-peptide receptor (FPR) family,
      appear to mediate the anti-inflammatory actions of this endogenous mediator.
      Administration of the annexin 1 N-terminal derived peptide Ac2-26 to mice after
      25 min ischemia significantly attenuated the extent of acute myocardial injury as
      assessed 60 min postreperfusion. Evident at the dose of 1 mg/kg (approximately 9
      nmol per animal), peptide Ac2-26 cardioprotection was intact in FPR null mice.
      Similarly, peptide Ac2-26 inhibition of specific markers of heart injury
      (specifically myeloperoxidase activity, CXC chemokine KC contents, and endogenous
      annexin 1 protein expression) was virtually identical in heart samples collected
      from wild-type and FPR null mice. Mouse myocardium expressed the mRNA for FPR and
      the structurally related lipoxin A4 receptor, termed ALX; thus, comparable
      equimolar doses of two ALX agonists (W peptide and a stable lipoxin A4 analog)
      exerted cardioprotection in wild-type and FPR null mice to an equal extent.
      Curiously, marked (>95%) blood neutropenia produced by an anti-mouse neutrophil
      serum did not modify the extent of acute heart injury, whereas it prevented the
      protection afforded by peptide Ac2-26. Thus, this study sheds light on the
      receptor mechanism(s) mediating annexin 1-induced cardioprotection and shows a
      pivotal role for ALX and circulating neutrophil, whereas it excludes any
      functional involvement of mouse FPR. These mechanistic data can help in
      developing novel therapeutics for acute cardioprotection.

PMID- 15507473
TI  - Methylation of histones in myeloid leukemias as a potential marker of granulocyte
      abnormalities.
AB  - We show that common heterochromatin antigenic protein markers [HP1alpha, -beta, 
      gamma and mono-, di-, and trimethylated histone H3 lysine 9 (H3K9)], although
      present in human blood progenitor CD34+ cells, differentiated lymphocytes, and
      monocytes, are absent in neutrophil granulocytes and to large extent, in
      eosinophils. Monomethylated and in particular, dimethylated H3K9 are present to
      variable degrees in the granulocytes of chronic myeloid leukemia (CML) patients,
      without being accompanied by HP1 proteins. In patients with an acute phase of CML
      and in acute myeloid leukemia patients, strong methylation of H3K9 and all
      isoforms of HP1 are detected. In chronic forms of CML, no strong correlations
      among the level of histone methylation, disease progression, and modality of
      treatment were observed. Histone methylation was found even in "cured" patients
      without Philadelphia chromosome (Ph) resulting from +(9;22)(q34;q11) BCR/ABL
      translocation, suggesting an incomplete process of developmentally regulated
      chromatin remodeling in the granulocytes of these patients. Similarly,
      reprogramming of leukemia HL-60 cells to terminal differentiation by retinoic
      acid does not eliminate H3K9 methylation and the presence of HP1 isoforms from
      differentiated granulocytes. Thus, our study shows for the first time that
      histone H3 methylation may be changed dramatically during normal cell
      differentiation. The residual histone H3 methylation in myeloid leukemia cells
      suggests an incomplete chromatin condensation that may be linked to the leukemia
      cell proliferation and may be important for the prognosis of disease treatment
      and relapse.

PMID- 15507474
TI  - Decreased resting energy expenditure in non-dialysed chronic kidney disease
      patients.
AB  - BACKGROUND: Non-dialysed chronic kidney disease (CKD) patients may have altered
      resting energy expenditure (REE) because of the important metabolic functions of
      the kidneys. The aim of the present study was to evaluate whether REE in
      clinically stable, non-diabetic and non-dialysed CKD patients with no clinical
      signs of inflammation, was different from that of gender and age pair-matched
      healthy controls. Subjects and methods. REE in 45 patients (20 male and 25
      female; age 44.9 +/- 11.7 years; mean +/- SD) and 45 healthy individuals (20 male
      and 25 female; age 44.6 +/- 11.5 years) was measured by indirect calorimetry
      after a 12-h fast. In both groups, body composition was assessed by bioelectrical
      impedance. Glomerular filtration rate was assessed by creatinine clearance only
      in the CKD patients. RESULTS: The mean creatinine clearance and serum creatinine
      of the CKD patients were 29.1 +/- 14.6 ml/min/1.73 m(2) and 3.48 +/- 2.48 mg/dl,
      respectively. Body fat (BF) and lean body mass (LBM) were similar between the two
      groups (CKD patients: BF 28.6 +/- 11.3%, LBM 46.9+/-10.0 kg; and healthy
      individuals: BF 28.1 +/- 7.54%, LBM 49.5 +/- 10.5 kg). REE of CKD patients was
      significantly lower than that of healthy individuals (1325 +/- 206 vs 1448 +/-
      258 kcal/day; P = 0.01, respectively) even after adjusting for LBM by multiple
      regression analysis. In fact, the presence of chronic renal insufficiency reduced
      REE by 103.2 kcal/day (P = 0.02; 95% confidence interval (-15.9; 190.5)).
      CONCLUSION: REE of clinically stable non-dialysed, non-diabetic patients in
      stages 2-5 of CKD was lower than that of age and gender pair-matched healthy
      individuals. Although the cause of reduced REE was unclear, it may be related to
      decreased food intake and to metabolic disturbances inherent with deterioration
      of renal function. Further studies will be necessary to clarify this issue.

PMID- 15507475
TI  - The growing volume of diabetes-related dialysis: a population based study.
AB  - BACKGROUND: End-stage renal failure requiring dialysis is one of the most serious
      complications of diabetes mellitus, and diabetes is the most common cause of end
      stage renal failure. The aim of this large, observational study is to describe
      the population-based incidence and prevalence rates and outcomes of diabetic
      individuals in Ontario, Canada who require dialysis therapy. METHODS: Two cohorts
      of patients, those with diabetes and those without, were created between April 1,
      1994 and March 31, 2000 (total of approximately 8.4 million) and followed until
      March 31, 2001 using several large, linked administrative databases at the
      Institute for Clinical Evaluative Sciences. The incidence, prevalence and
      mortality on dialysis for each cohort were determined. A multivariate Cox
      proportional hazards analysis, adjusting for age, sex and co-morbidity, was used
      to determine the independent impact of diabetes on patient survival. RESULTS: The
      average annual incidence rate of dialysis was 12 times greater in persons with
      diabetes (130 per 100,000) vs without diabetes (11 per 100,000). By 1999-2000,
      diabetic patients comprised 51% of the incident dialysis population. The average
      annual prevalence rate was 10 times greater in the diabetic cohort. Patients with
      diabetes had more co-morbidities at the start of dialysis and poorer 3 year
      survival (55 vs 68%; P < 0.0001). CONCLUSIONS: The incident and prevalent rates
      of dialysis for patients with diabetes mellitus are many times the rates of those
      without diabetes. Patients with diabetes mellitus often start dialysis with
      significant co-morbidities, which may contribute to the relatively high rate of
      mortality on dialysis.

PMID- 15507476
TI  - L-2-oxothiazolidine-4-carboxylic acid reduces in vitro cytotoxicity of glucose
      degradation products.
AB  - BACKGROUND: Glucose degradation products (GDP) are an important factor that
      contribute to bioincompatibility of peritoneal dialysis fluids. These substances
      are generated in the dialysis fluid during heat sterilization. Several approaches
      have been proposed to reduce the content or toxicity, or both, of GDP present in
      the dialysis fluid. We examined whether L-2-oxothiazolidine-4-carboxylic acid
      (OTZ), a precursor for glutathione synthesis, reduces the cytotoxicity of GDP in
      human peritoneal mesothelial cells. METHODS: Experiments were performed on
      primary mesothelial cell cultures. Free radical generation in these cells after
      exposure to acetaldehyde (ACT), glyoxal (GLYO) or methylglyoxal (M-GLYO) was
      detected with a fluorescent probe. Cell viability measurements were based on
      release of LDH from cell cytosol, and synthesis of IL-6 and proliferation after
      exposure to GDP. Effects of individual GDPs and of dialysis fluid free of GDP
      (GDP-free PDF) or containing GDP (GDP-high PDF) on cell viability were also
      studied in the presence of OTZ (1 mmol/l). RESULTS: All of the GDPs as well as
      the autoclaved dialysis fluid caused increased free radical generation. ACT
      increased LDH release from the cells by 374% (P < 0.001), and this effect was
      abolished by OTZ. All of the GDPs inhibited cell growth (ACT, 47%, P < 0.01;
      GLYO, 52%, P < 0.01; M-GLYO, 26%, P < 0.05) and this effect was reversed in
      presence of OTZ. ACT inhibited Il-6 synthesis in mesothelial cells by 74% P <
      0.01 and this effect was prevented by OTZ. GDP-high PDF but not GDP-free PDF
      reduced synthesis of IL-6 in mesothelial cells by 40% (P < 0.01) an effect that
      was reversed by OTZ. Mesothelial cell growth was more strongly inhibited by GDP
      high PDF (76%, P < 0.01) than by GDP-free PDF (31%, P < 0.05). OTZ improved
      growth of mesothelial cells in the presence of GDP-high PDF (+150%, P < 0.01) and
      in presence of GDP-low PDF (+38%, P < 0.05). OTZ prevented the cytotoxic effect
      of GDP-high PDF on mesothelial cells. CONCLUSIONS: The GDP-induced stimulation of
      free radicals in mesothelial cells in the present study may provide a possible
      mechanism of GDP cytotoxicity. Because OTZ reduced the toxic effects of GDP on
      mesothelial cells, this compound may improve biocompatibility of peritoneal
      dialysis fluids.

PMID- 15507477
TI  - Treatment of focal and segmental glomerulosclerosis in adults with tacrolimus
      monotherapy.
AB  - BACKGROUND: Focal segmental glomerulosclerosis (FSGS) commonly presents with
      nephrotic syndrome (NS), and spontaneous remission is rare. NS is a poor
      prognostic marker for renal survival, and has serious extra-renal complications.
      Rapid remission using drugs with minimal side effects is desirable. Tacrolimus
      (Tac) has a more potent immunosuppressive effect and may be less toxic at
      therapeutic doses than ciclosporin (CsA). Although CsA has a role in the
      treatment of FSGS, there are limited data regarding the use of Tac monotherapy in
      this setting, and this is limited to experience in children. METHODS: We
      prospectively report the outcome for six adult patients with FSGS treated with
      Tac from first presentation with NS, and for a further five adult patients in
      remission on CsA converted to Tac in an attempt to arrest a progressive decline
      in renal function on CsA. RESULTS: All six patients treated with Tac from
      presentation with NS achieved remission after 6.5 +/- 5.9 months. The serum
      albumin for the group increased from 26.8 +/- 4.6 to 37.7 +/- 1.9 g/l (P =
      0.003), and there was a significant reduction in the mean 24 h urinary protein
      excretion from 11.0 +/- 4.5 to 2.8 +/- 2.5 g (P = 0.003). All remissions were
      partial with a mean reduction in 24 h urinary protein of 75.2 +/- 16.8%. There
      was a non-significant reduction in MDRD GFR from 71.7 +/- 22.4 to 55.9 +/- 9.7
      ml/min/1.73 m(2) (P = 0.07), which manifest within the first 3 months of Tac
      treatment but renal function was subsequently stable. The mean follow-up for the
      group was 12.8+/-5.5 months. Two of the five patients converted from CsA to Tac
      maintained complete remission, and the remaining three patients in partial
      remission had further reductions in proteinuria. There was an improvement in
      renal function concomitant with conversion to Tac in each case, with an overall
      improvement in MDRD GFR for the group of +1.9+/-1.1 ml/min/1.73 m(2)/month.
      CONCLUSIONS: Tac rapidly and effectively induced remission of NS in FSGS.
      Conversion from CsA to Tac indicates that Tac might be a more potent agent with
      less nephrotoxicity in this setting.

PMID- 15507478
TI  - The growing family of hereditary renal cell carcinoma.

PMID- 15507479
TI  - The Czech registry of renal biopsies. Occurrence of renal diseases in the years
      1994-2000.
AB  - BACKGROUND: This report describes data collected by the Czech Registry of Renal
      Biopsies (CRRB). METHODS: Twenty-eight centres provided data on all biopsies of
      native kidneys performed in the Czech Republic (population 10.3 million) over the
      period 1994-2000. Data on serum creatinine concentration (sCr), 24 h proteinuria,
      haematuria, serum albumin level, arterial hypertension, diabetes mellitus,
      histological diagnosis and complications after renal biopsy were collected.
      RESULTS: Altogether 4004 biopsies in 3874 patients were performed (males 57.9%,
      children < or = 15 years 17.7%, elderly >60 years 14.3%). Microhaematuria was
      present in 65.9%, macrohaematuria in 9.2%, nephrotic proteinuria (> or = 3.5 g/24
      h) in 39.3%, and low-grade proteinuria (<3.5 g/24 h) in 41.4%. Among adults,
      hypertension was present in 45.2%, mild renal insufficiency in 23% (sCr 111-200
      micromol/l) and advanced renal insufficiency in 13.7% (sCr 201-400), while 11.5%
      of patients had sCr >400 micromol/l. The most frequent renal diseases were
      primary (59.8%) and secondary (25.4%) glomerulonephritis (GN). Tubulointerstitial
      nephritis (TIN) was observed in 4.4% and hypertensive nephroangiosclerosis in
      3.4%. The samples were non-diagnostic in 4.6%. Among primary GNs, the most
      frequent diagnoses were: IgA nephropathy (IgAN) 34.5%, minimal change disease
      (MCD) 12.4%, non-IgA mesangioproliferative GN (MesGN) 11.3%, focal segmental
      glomerulosclerosis (FSGS) 10.8% and membranous GN (MGN) 9.3%. Among secondary
      GNs, systemic lupus erythematosus (SLE) represented 23.0%, necrotizing vasculitis
      (NV) 15.5%, Henoch-Schonlein purpura 5.7%, thin basement membrane glomerulopathy
      (TBN) 19.3%, Alport syndrome 6.9%, renal amyloidosis 9.9% and myeloma kidney
      2.9%. Among children, the most common were IgAN (19.2%), MCD (17.6%) and TBM
      glomerulopathy (12.3%), while among the elderly the most common were MGN (11.0%),
      NV (10.7%) and amyloidosis (9.6%). The most common in patients with nephrotic
      proteinuria were MCD (50.5%) among children, but IgAN (24.6%) in adults aged 16
      60 years and MGN (16.8%) among the elderly. IgAN (21.3%) and FSGS (8.3%) were the
      most common diagnoses among patients with mild renal insufficiency, but TIN
      (11.6%) and NV (11.3%) were the most common in more advanced renal insufficiency.
      Since 1999, diabetic patients represented 12.2% of adults, with mean proteinuria
      8.9 g/24 h; diabetic glomerulosclerosis was found in 42.4% (with microhaematuria
      present in 66%) and non-diabetic renal diseases in 47.5% (IgAN in 17.5%, MGN and
      NAS in 11.1% and NV in 9.5%). The mean annual incidence (per million population)
      was: primary GN 32.4, secondary GN 13.8, IgAN 11.2, MCD 4.0, MesGN 3.7, FSGS 3.5,
      SLE 3.2, MGN 3.0, TBM 2.7, TIN 2.4 and NV 2.1. Ultrasound needle guidance was
      used in 56%, preferably in children (79%). The frequency of serious complications
      (gross haematuria, symptomatic haematoma, blood transfusion) remained at 3%.
      CONCLUSION: The CRRB provides important data on the epidemiology of GN based on a
      whole country population.

PMID- 15507480
TI  - AL-amyloidosis is underdiagnosed in renal biopsies.
AB  - BACKGROUND: Renal amyloidosis is associated with a variety of underlying disease
      processes. Although amyloid is identical in appearance in these diseases, the
      precursor proteins are different. Immunofluorescence microscopy has been used as
      the primary tool in the diagnostic evaluation of the underlying cause of renal AL
      amyloidosis. The purpose of this study was to document the sensitivity of
      immunofluorescence microscopy in AL-amyloidosis. METHODS: We reviewed 36 renal
      biopsies from patients with amyloidosis collected in two medical centres. All
      biopsies showed characteristic fibrillary deposits of amyloid on electron
      microscopy and stained positive with Congo red or Thioflavin-T. RESULTS: Among
      these 36 patients, immunofluorescence staining for lambda and kappa light chains
      was negative or equivocal in 14 biopsies. Of these 14 patients, two patients had
      evidence of AA-amyloidosis. Twelve patients were found subsequently to have a
      plasma cell dyscrasia or multiple myeloma with monoclonal immunoglobulin and/or
      free light chains on immunofixation electrophoresis of urine or serum, and with
      evaluation of the bone marrow. Thus, 12 of 34 patients (35.3%) with proven AL
      amyloidosis had negative immunofluorescence staining for kappa and lambda light
      chains. CONCLUSIONS: The data demonstrated the low sensitivity of
      immunofluorescence microscopy in the detection of AL-amyloidosis in the kidney
      and underscore the need to pursue additional diagnostic studies to identify this
      problem.

PMID- 15507481
TI  - Impact of the type of dialyser on the clinical outcome in chronic haemodialysis
      patients: does it really matter?

PMID- 15507482
TI  - Platelet-activating factor stimulates cytoplasmic alkalinization and granule
      acidification in human eosinophils.
AB  - The effects of platelet-activating factor (PAF) and IL-5 on intracellular pH were
      investigated in human eosinophils. Purified peripheral blood eosinophils were
      loaded with the ratiometric fluorescent pH indicator BCECF-AM ester. Stimulation
      of eosinophils with PAF produced time-dependent alkalinization of the cytoplasm
      from an initial pH of 7.1+/-0.04 to 7.5+/-0.05. A similar alkalinization response
      was produced by the calcium ionophore, ionomycin and by the calcium ATPase
      inhibitor, thapsigargin. These compounds as well as PAF produce significant
      increases in cytoplasmic calcium ([Ca2+]i). In contrast, IL-5 and the protein
      kinase C (PKC) activator phorbol myristate acetate (PMA) did not produce
      cytoplasmic alkalinization and had no effect on [Ca2+]i in eosinophils. PAF
      stimulated alkalinization was not inhibited under conditions that blocked plasma
      membrane Na+-H+ exchange, proton channel or plasma membrane H+-ATPase activities.
      Measurements of intragranule pH with a cell permeant pH indicator (LysoSensor
      Yellow/Blue DND-160), which partitions into intracellular acidic compartments,
      revealed that PAF-stimulated cytosolic alkalinization correlated with
      intragranule acidification. These results suggest that the increase in [Ca2+]i
      after PAF stimulation activates a H+-ATPase present in the granule membranes,
      leading to enhanced granule acidification and cytoplasmic alkalinization. We
      propose that granule acidification is an important step in solubilization of
      major basic protein crystals, which are stored within the granule core, in
      preparation for degranulation and release of these proteins.

PMID- 15507483
TI  - Calcium-mediated protein secretion potentiates motility in Toxoplasma gondii.
AB  - Apicomplexans such as Toxoplasma gondii actively invade host cells using a unique
      parasite-dependent mechanism termed gliding motility. Calcium-mediated protein
      secretion by the parasite has been implicated in this process, but the precise
      role of calcium signaling in motility remains unclear. Here we used calmidazolium
      as a tool to stimulate intracellular calcium fluxes and found that this drug led
      to enhanced motility by T. gondii. Treatment with calmidazolium increased the
      duration of gliding and resulted in trails that were twice as long as those
      formed by control parasites. Calmidazolium also increased microneme secretion by
      T. gondii, and studies with a deletion mutant of the accessory protein m2AP
      specifically implicated that adhesin MIC2 was important for gliding. The effects
      of calmidazolium on gliding and secretion were due to increased release of
      calcium from intracellular stores and calcium influx from the extracellular
      milieu. In addition, we demonstrate that calmidazolium-stimulated increases in
      intracellular calcium were highly dynamic, and that rapid fluxes in calcium
      levels were associated with parasite motility. Our studies suggest that
      oscillations in intracellular calcium levels may regulate microneme secretion and
      control gliding motility in T. gondii.

PMID- 15507484
TI  - FLICE/caspase-8 activation triggers anoikis induced by beta1-integrin blockade in
      human keratinocytes.
AB  - Beta1-integrin protects keratinocyte stem cells (KSC) from cell-detachment
      apoptosis ('anoikis'). Here we show that caspase-8 active protein is detected in
      both young transit amplifying (TA) cells and TA cells, but not in KSC. On
      suspension, caspases are activated earlier in young TA than in KSC, whereas anti
      beta1-integrin neutralizing antibody accelerates caspase activation in both KSC
      and young TA. Caspases 8 and 10 are the first caspases to be activated whereas
      caspase-8 inhibitor zIETD-fmk delays the activation of Bid, caspase-9 and caspase
      3. However, the caspase-9 inhibitor zLEDH-fmk does not block the activation of
      caspase-8, Bid, caspase-10 and caspase-3. Moreover, caspase-8, but not caspase-9
      inhibitor partially prevents keratinocyte anoikis. As FLIP inhibits caspase-8
      processing, we retrovirally infected HaCaT keratinocytes with c-FLIP(L). Anti
      beta1-integrin fails to activate caspase-8, Bid, caspase-9 and to induce the
      release of cytochrome c in c-FLIP(L) overexpressing keratinocytes. Finally,
      overexpression of c-FLIP(L) partially prevents anoikis in both suspended and anti
      beta1 integrin-treated cells. Taken together, these results indicate that the
      extrinsic apoptotic pathway triggered by caspase-8 predominates in keratinocyte
      anoikis. However, the release of cytochrome c and the later activation of caspase
      9 seem to suggest that the intrinsic mitochondrial pathway may intervene as a
      positive feedback loop of caspase activation.

PMID- 15507485
TI  - Truncated TrkB receptor-induced outgrowth of dendritic filopodia involves the p75
      neurotrophin receptor.
AB  - The Trk family of receptor tyrosine kinases and the p75 receptor (p75NTR) mediate
      the effects of neurotrophins on neuronal survival, differentiation and synaptic
      plasticity. The neurotrophin BDNF and its cognate receptor tyrosine kinase,
      TrkB.FL, are highly expressed in neurons of the central nervous system. At later
      stages in postnatal development the truncated TrkB splice variants (TrkB.T1,
      TrkB.T2) become abundant. However, the signalling and function of these truncated
      receptors remained largely elusive. We show that overexpression of TrkB.T1 in
      hippocampal neurons induces the formation of dendritic filopodia, which are known
      precursors of synaptic spines. The induction of filopodia by TrkB.T1 occurs
      independently of neurotrophin binding and of kinase activity of endogenous
      TrkB.FL. Coexpression of a p75NTR lacking an intracellular domain inhibits the
      TrkB.T1-induced effect in a dominant negative manner. Steric hindrance of
      extracellular p75NTR interactions with a specific antibody, or absence of p75NTR
      with an intact extracellular domain also inhibit this TrkB.T1-induced effect. We
      thus propose a novel signalling pathway initiated by neurotrophin-independent
      extracellular or intramembrane interaction of TrkB.T1 with the p75NTR receptor,
      which modulates dendritic growth via p75NTR signalling cascades.

PMID- 15507486
TI  - Differential actin binding along the PEVK domain of skeletal muscle titin.
AB  - Parts of the PEVK (Pro-Glu-Val-Lys) domain of the skeletal muscle isoform of the
      giant intrasarcomeric protein titin have been shown to bind F-actin. However, the
      mechanisms and physiological function of this are poorly understood. To test for
      actin binding along PEVK, we expressed contiguous N-terminal (PEVKI), middle
      (PEVKII), and C-terminal (PEVKIII) PEVK segments of the human soleus muscle
      isoform. We found a differential actin binding along PEVK in solid-state binding,
      cross-linking and in vitro motility assays. The order of apparent affinity is
      PEVKII>PEVKI>PEVKIII. To explore which sequence motifs convey the actin-binding
      property, we cloned and expressed PEVK fragments with different motif structure:
      PPAK, polyE-rich and pure polyE fragments. The polyE-containing fragments had a
      stronger apparent actin binding, suggesting that a local preponderance of polyE
      motifs conveys an enhanced local actin-binding property to PEVK. The actin
      binding of PEVK may serve as a viscous bumper mechanism that limits the velocity
      of unloaded muscle shortening towards short sarcomere lengths. Variations in the
      motif structure of PEVK might be a method of regulating the magnitude of the
      viscous drag.

PMID- 15507487
TI  - Salmonella typhimurium transcytoses flagellin via an SPI2-mediated vesicular
      transport pathway.
AB  - Apical colonization of polarized epithelia by Salmonella typhimurium results in
      translocation of flagellin to the basolateral membrane domain, thus enabling
      activation of toll-like receptor 5 (TLR5)-mediated pro-inflammatory gene
      expression. Such flagellin transcytosis occurred without a change in epithelial
      permeability to 40 kDa FITC dextran, did not require bacterial motility and was
      independent of transepithelial movement of intact bacteria. Flagellin
      transcytosis was blocked at 20 degrees C, suggesting dependence on vesicular
      transport consistent with results from confocal microscopy that showed flagellin
      independent of bacteria inside epithelial cells. Furthermore, vesicles isolated
      from S. typhimurium-infected epithelia were highly enriched in flagellin.
      Flagellin transcytosis was dependent upon genes of Salmonella pathogenicity
      island (SPI)-2, which alter vesicular trafficking, but independent of SPI-1 that
      mediates bacterial invasion. Furthermore, such SPI-2 mutants were unable to
      mediate the localization of flagellin into intracellular vesicles consistent with
      flagellin transcytosis mediated by a S. typhimurium take-over of host vesicle
      trafficking pathways. As a result of their inability to transcytose flagellin,
      apical colonization by SPI-2 mutants induced substantially less epithelial IL-8
      secretion than wild-type strains suggesting that such SPI-2 mediated transcytosis
      of flagellin plays a role in the pathogenesis of the mucosal inflammation
      characteristic of human Salmonellosis.

PMID- 15507488
TI  - Translocation of the Dictyostelium TRAP1 homologue to mitochondria induces a
      novel prestarvation response.
AB  - Dd-TRAP1 is a Dictyostelium homologue of tumor necrosis factor receptor
      associated protein 1 (TRAP-1). Dd-TRAP1 is located in the cortex of cells growing
      at a low density, but was found to be translocated to mitochondria with the help
      of a novel prestarvation factor that was accumulated in growth medium along with
      increased cell densities. The knockdown mutant of Dd-TRAP1 (TRAP1-RNAi cells)
      exhibited a significant defect in prestarvation response. Although TRAP1-RNAi
      cells showed normal expressions of classical prestarvation genes [dscA (discoidin
      I) and car1 (carA; cAMP receptor)], the expression of differentiation-associated
      genes (dia1 and dia3) induced by the prestarvation response were markedly
      repressed. By contrast, transformants overexpressing Dd-TRAP1 showed an early
      prestarvation response and also increased expression of dia1 and dia3 in a cell
      density-dependent manner. Importantly, introduction of Dd-TRAP1 antibody into D.
      discoideum Ax-2 cells by electroporation inhibited the translocation of Dd-TRAP1
      from the cortex to mitochondria and greatly inhibited the initiation of
      differentiation. Taken together, these results indicate that Dd-TRAP1 is
      translocated to mitochondria by sensing the cell density in growth medium and
      enhances the early developmental program through a novel prestarvation response.

PMID- 15507489
TI  - Theories of change: what works in improving health in mid-life?
AB  - The need to promote healthy active ageing in order to offset the impact of an
      ageing population on national resources and ensure a high quality of life in
      older age is well recognized. In 2001, the English Department of Health
      established a national pre-retirement health initiative involving the development
      of eight pilot projects. A national evaluation using a 'theories of change'
      approach embedded within a realistic evaluation design was commissioned to draw
      out the lessons from across the projects. In this article we describe the methods
      used to identify and test out the projects' theories of change, and the results
      obtained. The theories of change identified revolved mainly around engaging
      clients and empowering them to take action through the provision of information.
      Two projects also saw providing opportunities for social interaction as a means
      to engaging and empowering clients. Theory testing indicated that health
      improvement services could be effectively targeted at people in mid-life and that
      service settings and style played an important part in engagement. In particular
      contexts, combining free health checks with financial advice was a significant
      motivator for engagement, as was perceived health need in two deprived areas.
      Gains in knowledge were also important for empowerment in some contexts, but
      validation of existing knowledge could be more important in others. Opportunities
      to engage in social activities were a potent mechanism for empowerment amongst
      women living in two deprived areas. Further work is required to test these
      conclusions in other contexts, and to ascertain how people from minority ethnic
      groups and men, particularly those outside the labour market, can be engaged in
      health improvement initiatives.

PMID- 15507490
TI  - The influence of the secondary school setting on the food practices of young
      teenagers from disadvantaged backgrounds in Scotland.
AB  - In this paper, we explore the secondary school environment as an important
      context for understanding young teenagers' eating habits and food practices. We
      draw on data collected during semi-structured interviews with 36 young teenagers
      (aged 13/14 years) living in disadvantaged circumstances in Scotland. We found
      that the systems inherent in school had an impact on what, where and when
      participants ate their lunch. Each school had rules governing use of the school
      dining hall and participants sometimes chose to leave this environment to buy
      food outside school premises. Our interviews showed that parents determined how
      much money young people took to school and, therefore, had some control over
      their food choices. Participants rarely spoke of giving priority to food and
      eating during the non-curriculum parts of the school day, preferring to spend
      time 'hanging out' with friends. Eating with friends was sometimes reported as a
      cause of anxiety, particularly when participants had concerns about body image,
      appetite or appearance. We suggest that young teenagers' dislike for queuing for
      food, their ability to budget for food at school and their desire to maximize
      time spent with friends influence food choices; therefore, these are issues which
      have implications for health education and will be of interest to those
      responsible for school meal provision.

PMID- 15507491
TI  - Molecular analysis of a locus control region in the T helper 2 cytokine gene
      cluster: a target for STAT6 but not GATA3.
AB  - The linked IL-4 and IL-13 cytokine genes, which are activated and silenced in T
      helper (Th) 2 and Th1 cells, respectively, are flanked by the equivalently
      expressed RAD50 and KIF3A genes. A scan of DNase I hypersensitivity and DNA
      methylation across approximately 100 kb of the KIF3A/IL-4/IL-13/RAD50 cluster
      revealed differences in chromatin structure between Th1 and Th2 cells at the 3'
      end of the RAD50 gene, a region previously shown to contain a locus control
      region (LCR) regulating Th2-specific expression of IL-4 and IL-13. Naive CD4 T
      cells did not exhibit any DNase I hypersensitivity in this region, but
      stimulation under either Th1 or Th2 conditions caused rapid development of three
      hypersensitive sites. An additional hypersensitive site developed rapidly only
      under Th2 conditions, through a mechanism dependent on signal transducers and
      activators of transcription 6 (STAT6) but not GATA3. Our data point to a physical
      separation in the actions of STAT6 and its downstream effector GATA3 during Th2
      differentiation: STAT6 directly remodels the RAD50 LCR, whereas GATA3 acts only
      in the vicinity of the IL-4 gene. We suggest that the RAD50 LCR has a complex and
      dual role in Th1 and Th2 differentiation, communicating early T cell antigen
      receptor and cytokine signals to the IL-4/IL-13 locus in both differentiating
      cell types.

PMID- 15507492
TI  - Human fatty acid synthase: structure and substrate selectivity of the
      thioesterase domain.
AB  - Human fatty acid synthase is a large homodimeric multifunctional enzyme that
      synthesizes palmitic acid. The unique carboxyl terminal thioesterase domain of
      fatty acid synthase hydrolyzes the growing fatty acid chain and plays a critical
      role in regulating the chain length of fatty acid released. Also, the up
      regulation of human fatty acid synthase in a variety of cancer makes the
      thioesterase a candidate target for therapeutic treatment. The 2.6-A resolution
      structure of human fatty acid synthase thioesterase domain reported here is
      comprised of two dissimilar subdomains, A and B. The smaller subdomain B is
      composed entirely of alpha-helices arranged in an atypical fold, whereas the A
      subdomain is a variation of the alpha/beta hydrolase fold. The structure revealed
      the presence of a hydrophobic groove with a distal pocket at the interface of the
      two subdomains, which constitutes the candidate substrate binding site. The
      length and largely hydrophobic nature of the groove and pocket are consistent
      with the high selectivity of the thioesterase for palmitoyl acyl substrate. The
      structure also set the identity of the Asp residue of the catalytic triad of Ser,
      His, and Asp located in subdomain A at the proximal end of the groove.

PMID- 15507494
TI  - Impact of prophylactic postoperative beta-blockade on post-cardiothoracic surgery
      length of stay and atrial fibrillation.
AB  - BACKGROUND: Previous studies have shown that post-cardiothoracic surgery atrial
      fibrillation (AF) increases the risk of hospital length of stay (LOS), overall
      mortality, pulmonary edema, and need for a balloon pump. A meta-analysis of 2
      previous trials showed a nonsignificant reduction in LOS with postoperative beta
      blockers but only encompassed 1200 patients, with few valve surgery patients, and
      neither study used a hospital within the US. OBJECTIVE: To evaluate the impact of
      postoperative beta-blockers on LOS and AF. Secondary endpoints of overall
      mortality, pulmonary edema, and need for an intra-aortic balloon pump (IABP) were
      also evaluated between groups. METHODS: This was a prospective cohort evaluation
      of all patients undergoing cardiothoracic surgery at our institution between
      October 1999 and October 2003. Patients receiving prophylactic postoperative beta
      blockers were matched (1:1) with patients not receiving prophylaxis for age >70
      years, valvular surgery, history of AF, gender, and use of preoperative digoxin
      and beta-blockers. RESULTS: Patients (n = 1660) receiving postoperative beta
      blockade had a reduction in LOS (mean +/- SD 10.22 +/- 11.38 vs 12.40 +/- 15.67;
      p = 0.001) and AF (23.5% vs 28.4%; p = 0.02). Mortality, pulmonary edema, and
      need for IABP were reduced by >50% (p < 0.001; p = 0.001; p < 0.001,
      respectively), while myocardial infarction and stroke were not significantly
      impacted. CONCLUSIONS: In this observational cohort study, prophylactic
      postoperative beta-blocker use was associated with shorter hospital LOS by an
      average of 2.2 days and a 17.3% lower incidence of AF. It may also be associated
      with reductions in overall mortality, pulmonary edema, and need for an IABP.

PMID- 15507493
TI  - Association of late-onset Alzheimer's disease with genetic variation in multiple
      members of the GAPD gene family.
AB  - Although several genes have been implicated in the development of the early-onset
      autosomal dominant form of Alzheimer's disease (AD), the genetics of late-onset
      AD (LOAD) is complex. Loci on several chromosomes have been linked to the
      disease, but so far only the apolipoprotein E gene has been consistently shown to
      be a risk factor. We have performed a large-scale single-nucleotide polymorphism
      (SNP)-based association study, across the region of linkage on chromosome 12, in
      multiple case-control series totaling 1,089 LOAD patients and 1,196 control
      subjects and report association with SNPs in the glyceraldehyde-3-phosphate
      dehydrogenase (GAPD) gene. Subsequent analysis of GAPD paralogs on other
      chromosomes demonstrated association with two other paralogs. A significant
      association between LOAD and a compound genotype of the three GAPD genes was
      observed in all three sample sets. Individually, these SNPs make differential
      contributions to disease risk in each of the casecontrol series, suggesting that
      variants in functionally similar genes may account for series-to-series
      heterogeneity of disease risk. Our observations raise the possibility that GAPD
      genes are AD risk factors, a hypothesis that is consistent with the role of GAPD
      in neuronal apoptosis.

PMID- 15507495
TI  - Population pharmacokinetics III: design, analysis, and application of population
      pharmacokinetic Studies.
AB  - OBJECTIVE: To present a framework within which population pharmacokinetic (PPK)
      studies should be designed and analyzed and discuss the application of developed
      PPK models. METHODS: Information on PPK was retrieved from a MEDLINE search (1979
      December 2003) of the literature and a bibliographic evaluation of review
      articles and books. This information is used in conjunction with experience to
      explain the design and analysis of PPK studies. Also, examples are included to
      demonstrate the usefulness of PPK. SYNTHESIS: A great deal of thought must be
      given to the design and analysis of PPK studies (ie, development of PPK models).
      Models are of 2 primary types--descriptive and predictive--and the process
      applied to these models is necessarily different. An approach that ensures model
      applicability is presented. CONCLUSIONS: PPK models have great utility, and the
      applications are many. They are very different from single-subject
      pharmacokinetic models and therefore require different approaches to model
      estimation.

PMID- 15507496
TI  - Documentation forms for patients with asthma: an evaluation.

PMID- 15507497
TI  - Pharmacist-run travel medicine clinic.

PMID- 15507498
TI  - Tenofovir therapy for lamivudine resistance following liver transplantation.
AB  - BACKGROUND: Resistant hepatitis B virus (HBV) strains develop in 30% of liver
      transplant recipients treated with lamivudine within 2 years from the time of
      transplantation. OBJECTIVE: To assess safety and outcomes of tenofovir salvage
      therapy for patients with lamivudine resistance in a retrospective cohort of
      liver-transplanted patients. METHODS: Medical records were retrospectively
      evaluated for patients who received tenofovir. Data collected included
      demographics, HBV serologic information prior to and during tenofovir therapy,
      drug-related complications, and creatinine clearance. Criteria for lamivudine
      resistance included elevation of liver chemistries along with reappearance of
      hepatitis B surface antigen, hepatitis Be antigen, and/or HBV DNA. RESULTS:
      Sixteen patients showed resistance to lamivudine at 10-85 months (median 26)
      following liver transplantation. Tenofovir 300 mg/day orally was added in 8
      patients 1-66 months after the development of viral lamivudine resistance and
      continued for 14-26 months (median 19.3). All 8 patients experienced HBV DNA
      viral suppression, with 7 currently nondetectable. No adverse events were
      reported, and creatinine clearance was not impaired. CONCLUSIONS: Our results
      suggest that tenofovir safely and markedly decreases replication of lamivudine
      resistant HBV variants after liver transplantation and is another potential
      option for the treatment of HBV lamivudine resistance.

PMID- 15507499
TI  - Informational content of official pharmaceutical industry web sites about
      treatments for erectile dysfunction.
AB  - BACKGROUND: In the last 5 years, several treatments have become available for
      erectile dysfunction (ED). During this same period, consumer use of the Internet
      for health information has increased rapidly. In traditional direct-to-consumer
      advertisements, viewers are often referred to a pharmaceutical company Web site
      for further information. OBJECTIVE: To evaluate the accessibility and
      informational content of 5 pharmaceutical company Web sites about ED treatments.
      METHODS: Using 10 popular search engines and 1 specialized search engine, the
      accessibility of the official pharmaceutical company-sponsored Web site was
      determined by searching under brand and generic names. One company also
      manufactures an ED device; this site was also included. A structured, explicit
      review of information found on these sites was conducted. RESULTS: Of 110
      searches (1 for each treatment, including corresponding generic drug name, using
      each search engine), 68 yielded the official pharmaceutical company Web site
      within the first 10 links. Removal of outliers (for both brand and generic name
      searches) resulted in 68 of 77 searches producing the pharmaceutical company Web
      site for the brand-name drug in the top 10 links. Although all pharmaceutical
      company Web sites contained general information on adverse effects and
      contraindications to use, only 2 sites gave actual percentages. Three sites
      provided references for their materials or discussed other treatment or drug
      options, while 4 of the sites contained profound advertising or emotive content.
      None mentioned cost of the therapy. CONCLUSIONS: The information contained on
      pharmaceutical company Web sites for ED treatments is superficial and aimed
      primarily at consumers. It is largely promotional and provides only limited
      information needed to effectively compare treatment options.

PMID- 15507500
TI  - Recurrent infusion phlebitis induced by cyclosporine.
AB  - OBJECTIVE: To report a case of recurrent infusion phlebitis during cyclosporine
      treatment, which, as of October 14, 2004, is a previously unreported adverse
      effect of this drug. CASE SUMMARY: A 28-year-old man previously diagnosed with
      ulcerative colitis was admitted to the internal medicine department due to
      exacerbation of the condition and treated with intravenous hydrocortisone,
      followed by treatment with intravenous cyclosporine. During this treatment, the
      patient experienced quick, recurrent, and significant infusion phlebitis. The
      intravenous catheter and its site needed to be replaced repeatedly during the
      continuum of treatment, eventually leading to complete remission of the
      ulcerative colitis. After 8 months, the patient was still in remission, with no
      permanent signs of damage to the involved phlebitic veins. DISCUSSION: Infusion
      phlebitis induced by drugs is a common phenomenon that causes pain and difficulty
      in a patient's treatment. Many drugs, mainly antibiotics and cytotoxic drugs,
      have previously been reported to induce infusion phlebitis. We describe the first
      report of a patient with cyclosporine-induced recurrent infusion phlebitis.
      According to the Naranjo probability scale, the relationship of the encountered
      phlebitis to cyclosporine therapy is probable. CONCLUSIONS: Recurrent infusion
      phlebitis is a previously unreported adverse effect encountered during treatment
      with cyclosporine. This important adverse effect must be considered when treating
      patients with this unique drug.

PMID- 15507501
TI  - Clinical pharmacy travel medicine services: a new frontier.
AB  - Travel to remote destinations has increased dramatically in recent years. The
      Clinical Pharmacy International Travel Clinic (CPITC) was established in 1991 in
      the Kaiser Permanente Colorado Region to provide pre-travel advice to members to
      decrease their risk of travel-related diseases. The CPITC is unique from other
      travel medicine clinics because it is a pharmacist-run telepharmacy service. The
      team includes an infectious diseases physician, an infectious diseases clinical
      pharmacy specialist, 4 clinical pharmacists, and a pharmacy technician. The
      clinical pharmacists provide consultations via telephone. Both patient- and trip
      related information are gathered to assess the traveler's health risks.
      Recommendations are provided regarding food- and water-borne diseases, insect
      borne diseases, sexually transmitted diseases, and diseases related to animal
      bites. Additionally, detailed information is provided on vaccines that may be
      needed to protect travelers against various diseases. The travel consult is
      documented electronically. A copy of the consult, along with a booklet that
      provides travel information, is mailed to the patient. Success of the CPITC is
      demonstrated in several ways. The clinic initially served Kaiser Permanente
      members in the Colorado Region. The service has expanded and now also provides
      travel consults to Kaiser Permanente members in the Northwest and Ohio Regions.
      Patient satisfaction is high, and significant cost-savings have been realized
      secondary to avoiding the use of unnecessary vaccinations and medications. The
      CPITC allows resources to be leveraged and provides one center where individuals
      trained in travel medicine provide information to members, thus improving
      efficiency and decreasing cost.

PMID- 15507502
TI  - Osteonecrosis in six HIV-infected patients receiving highly active antiretroviral
      therapy.
AB  - OBJECTIVE: To report 6 cases of osteonecrosis in HIV-infected patients treated
      with highly active antiretroviral therapy (HAART) and compare the observed risk
      factors with those of published cases. CASE SUMMARIES: Osteonecrosis was
      diagnosed between 1999 and 2002 in 6 of 417 HIV-infected patients in our
      department of infectious diseases. At the time of diagnosis, mean patient age was
      42 years, and 5 patients had developed AIDS. Mean CD4+ lymphocyte count was 563.5
      cells/mm(3) and viral load was undetectable (<50 copies/mL) in 5 patients. The
      patients' mean body mass index was 22.5 kg/m(2). Four had lipodystrophy. All were
      receiving HAART, including a protease inhibitor in 4 patients; the remaining 2
      patients had a history of protease inhibitor treatment. Median time from the
      first antiretroviral therapy to osteonecrosis diagnosis was 46.5 months.
      Established risk factors were the use of corticosteroids in 2 patients and
      dyslipidemia in all patients. All of the patients developed pain and functional
      impotence of the hip or ankle joints. Osteonecrosis of the hip was bilateral in 4
      cases. Three patients required surgical intervention, all of whom had favorable
      outcomes. DISCUSSION: HIV-infected patients are at a higher risk for the
      development of osteonecrosis and are more likely to be exposed to predisposing
      factors to its development. The HAART implication as a predisposing factor
      remains controversial. CONCLUSIONS: The pathogenesis of osteonecrosis in HIV
      infected individuals may be multifactorial; the reasonable approach for
      clinicians consists of treating concomitant predisposing conditions that might
      further cause osteonecrosis.

PMID- 15507503
TI  - Sedative drug use in the home-dwelling elderly.
AB  - BACKGROUND: The elderly use more sedatives than other populations. Reports on the
      sedative load of drugs and their associations with health items are scarce.
      OBJECTIVE: To investigate the prevalence of sedatives and drugs with sedative
      properties and the associations between those drugs and demographic or health
      items in the home-dwelling elderly in a cross-sectional community survey.
      METHODS: Information was obtained from 1197 persons (43% men) aged >or=64 years
      in the Finnish municipality of Lieto in 1998-1999. The brand names of the
      prescription drugs taken by each interviewee during one week prior to the
      interview were recorded. The classification created in a previous study, where
      the drugs used in Finland were divided into 4 groups by their sedative
      properties, was utilized to determine associations with health items. RESULTS: A
      total of 88% (n = 1056) of the participants used some drug. Forty percent (n =
      422 persons) of the drug users took sedatives or drugs with sedative properties.
      The oldest individuals (>or=80 y), women, those with low education, smokers,
      those with poor self-perceived health, people with dementia and mobility
      problems, and especially those with depression had an independent association
      with the simultaneous use of many (>or=2) sedatives or drugs with sedative
      properties. CONCLUSIONS: In a population of home-dwelling elderly patients,
      abundant sedative drug use was common and especially associated with high age,
      female gender, poor basic education, poor health habits (eg, smoking),
      depression, dementia, or impaired mobility. Users also had poor self-perceived
      health. The need to further develop the classification will be a major challenge,
      and the classification needs to be updated every year. More studies are needed in
      this field.

PMID- 15507504
TI  - The potential role of HMG-CoA reductase inhibitors in pediatric nephrotic
      syndrome.
AB  - OBJECTIVE: To evaluate the safety and efficacy of the hydroxymethylglutaryl
      coenzyme A (HMG-CoA) reductase inhibitors (statins) as a potential treatment
      option for the dyslipidemia associated with childhood nephrotic syndrome. DATA
      SOURCES: Searches of MEDLINE (1966-April 2004), Cochrane Library, International
      Pharmaceutical Abstracts (1977-April 2004), and an extensive manual review of
      journals were performed using the key search terms nephrotic syndrome, familial
      hypercholesterolemia, dyslipidemia, and HMG-CoA reductase inhibitor. STUDY
      SELECTION AND DATA EXTRACTION: Two prospective uncontrolled studies evaluating
      the safety and efficacy of statin therapy in pediatric nephrotic syndrome were
      included. DATA SYNTHESIS: While an extensive amount of data is available in adult
      nephrotic syndrome in which statin therapy decreases total plasma cholesterol 22
      39%, low-density lipoprotein cholesterol (LDL-C) 27-47%, and total plasma
      triglycerides 13-38%, only 2 small uncontrolled studies have been conducted
      evaluating the utility of these agents in pediatric nephrotic syndrome. These
      studies indicate that statins are capable of safely reducing total cholesterol up
      to 42%, LDL-C up to 46%, and triglyceride levels up to 44%. CONCLUSIONS: Lowering
      cholesterol levels during childhood may reduce the risk for atherosclerotic
      changes and may thus be of benefit in certain patients with nephrotic syndrome.
      Statins have demonstrated short-term safety and efficacy in the pediatric
      nephrotic syndrome population. Implementing pharmacologic therapy with statins in
      children with nephrotic syndrome must be done with care until controlled studies
      are conducted in this population.

PMID- 15507505
TI  - Thyroid hormone responsive genes in cultured human fibroblasts.
AB  - Human skin fibroblasts are readily accessible cells for propagation in culture
      without transformation that can serve for direct pathophysiology studies in
      subjects with inherited diseases. We thus examined by quantitative fluorescent
      cDNA microarray analysis the effect of thyroid hormone (TH) on the expression of
      more than 15,000 genes in fibroblasts of two normal individuals. Fibroblasts from
      two subjects with resistance to thyroid hormone (RTH) due to mutations in the TH
      receptor-beta gene were used to confirm the specificity of the hormonal effect by
      the ability to discriminate between normal cells and cells with a defect in TH
      action. Microarray analysis identified 148 genes induced by 1.4-fold or more and
      five genes repressed to 0.7 or less 24 h after treatment with 2 x 10(-9) M T(3).
      Taking into account duplicate genes, these represented 91 up-regulated and five
      down-regulated genes, respectively. Confirmation by real-time PCR was obtained in
      eight of 10 induced and two of three repressed genes that were tested. Further
      evidence for T(3)-specific induction was provided by a graded dose response
      absent in fibroblasts from the patients with RTH. The following genes not
      previously known to be induced by TH were identified and validated: aldo-keto
      reductase family 1 C1-3, collagen type VI alpha 3, member RAS oncogene family
      brain antigen RAB3B, platelet phosphofructokinase, hypoxia-inducible factor-1
      alpha, and enolase 1 alpha. These genes as well as three known to be TH regulated
      in other species and found in this study also in human cells (glucose transporter
      1, solute carrier family 16 member 3, and basic transcription element-binding
      protein 1) have a variety of regulatory functions in development and metabolism.
      TH seems to induce these genes by initiating either genomic or nongenomic
      mechanisms. Surprisingly, TH-mediated down-regulation of fibroblast growth factor
      7 and alcohol dehydrogenase 1B persisted in fibroblasts from patients with RTH.
      This first systematic study of TH-mediated gene expression in normal human cells
      identifies several new TH-responsive genes and demonstrates that skin fibroblasts
      are suitable for the study of TH action in health and disease.

PMID- 15507506
TI  - Homozygous disruption of P450 side-chain cleavage (CYP11A1) is associated with
      prematurity, complete 46,XY sex reversal, and severe adrenal failure.
AB  - Disruption of the P450 side-chain cleavage cytochrome (P450scc) enzyme due to
      deleterious mutations of the CYP11A1 gene is thought to be incompatible with
      fetal survival because of impaired progesterone production by the fetoplacental
      unit. We present a 46,XY patient with a homozygous disruption of CYP11A1. The
      child was born prematurely with complete sex reversal and severe adrenal
      insufficiency. Laboratory data showed diminished or absent steroidogenesis in all
      pathways. Molecular genetic analysis of the CYP11A1 gene revealed a homozygous
      single nucleotide deletion leading to a premature termination at codon position
      288. This mutation will delete highly conserved regions of the P450scc enzyme and
      thus is predicted to lead to a nonfunctional protein. Both healthy parents were
      heterozygous for this mutation. Our report demonstrates that severe disruption of
      P450scc can be compatible with survival in rare instances. Furthermore, defects
      in this enzyme are inherited in an autosomal-recessive fashion, and heterozygote
      carriers can be healthy and fertile. The possibility of P450scc-independent
      pathways of steroid synthesis in addition to the current concept of
      luteoplacental shift of progesterone synthesis in humans has to be questioned.

PMID- 15507507
TI  - Adenovirally mediated expression of insulin-like growth factors enhances the
      function of first trimester placental fibroblasts.
AB  - IGFs are critical in fetal growth because of their role in placental development
      and function. In this study, we used adenovirus (Ad-IGF) to deliver sense or
      antisense IGF-I or IGF-II cDNA to human primary placental fibroblasts (PPF) in
      vitro to determine whether this could lead to enhanced placental cell function.
      PPFs virally transfected with Ad-IGF-I or Ad-IGF-II showed 7-fold (P < 0.01) and
      3-fold (P < 0.01) increases in [(3)H]thymidine incorporation at 48 h post
      infection compared with nontransfected controls. In a coculture system designed
      to assess cell migration, nontransfected PPF cells positioned over a monolayer
      transfected by Ad-IGF-I or Ad-IGF-II showed a more than 10-fold (P < 0.01) and a
      7-fold (P < 0.01) increase in migration compared with cells positioned above a
      nontransfected monolayer. After 96 h in culture, PPFs transfected with sense Ad
      IGF-I or Ad-IGF-II showed 2% apoptosis compared with 16% of nontransfected cells,
      whereas 37% and 25% of cells transfected with antisense Ad-IGF-I or Ad-IGF-II
      were apoptotic. This work has established that cells of placental origin are
      amenable to adenoviral transfection and that IGFs exert autocrine and paracrine
      effects on proliferation, migration, and survival, suggesting that enhancement of
      IGF levels in the placenta may augment placental function and increase fetal
      growth.

PMID- 15507508
TI  - Interaction between calcium intake and menarcheal age on bone mass gain: an eight
      year follow-up study from prepuberty to postmenarche.
AB  - Both late menarcheal age and low calcium intake (Ca intake) during growth are
      risk factors for osteoporosis, probably by impairing peak bone mass. We
      investigated whether lasting gain in areal bone mineral density (aBMD) in
      response to increased Ca intake varies according to menarcheal age and,
      conversely, whether Ca intake could influence menarcheal age. In an initial
      study, 144 prepubertal girls were randomized in a double-blind controlled trial
      to receive either a Ca supplement (Ca-suppl.) of 850 mg/d or placebo from age 7.9
      8.9 yr. Mean aBMD gain determined by dual energy x-ray absorptiometry at six
      sites (radius metaphysis, radius diaphysis, femoral neck, trochanter, femoral
      diaphysis, and L2-L4) was significantly (P = 0.004) greater in the Ca-suppl. than
      in the placebo group (27 vs. 21 mg/cm(2)). In 122 girls followed up, menarcheal
      age was recorded, and aBMD was determined at 16.4 yr of age. Menarcheal age was
      lower in the Ca-suppl. than in the placebo group (P = 0.048). Menarcheal age and
      Ca intake were negatively correlated (r = -0.35; P < 0.001), as were aBMD gains
      from age 7.9-16.4 yr and menarcheal age at all skeletal sites (range: r = -0.41
      to r = -0.22; P < 0.001 to P = 0.016). The positive effect of Ca-suppl. on the
      mean aBMD gain from baseline remained significantly greater in girls below, but
      not in those above, the median of menarcheal age (13.0 yr). Early menarcheal age
      (12.1 +/- 0.5 yr): placebo, 286 +/- 36 mg/cm(2); Ca-suppl., 317 +/- 46 (P =
      0.009); late menarcheal age (13.9 +/- 0.5 yr): placebo, 284 +/- 58; Ca-suppl.,
      276 +/- 50 (P > 0.05). The level of Ca intake during prepuberty may influence the
      timing of menarche, which, in turn, could influence long-term bone mass gain in
      response to Ca supplementation. Thus, both determinants of early menarcheal age
      and high Ca intake may positively interact on bone mineral mass accrual.

PMID- 15507509
TI  - CYP11B2-CYP11B1 haplotypes associated with decreased 11 beta-hydroxylase
      activity.
AB  - Reduced adrenal 11 beta-hydroxylation has been associated with an aldosterone
      synthase (CYP11B2) polymorphism. The 11 beta-hydroxylase gene (CYP11B1) lies
      close to CYP11B2. We hypothesize that a molecular variant in CYP11B2 is in
      linkage disequilibrium (LD) with a key quantitative trait in CYP11B1 determining
      this phenotype. Polymorphisms and inferred haplotypes at CYP11B loci were studied
      in two independent populations from Europe (n = 100) and South America (n = 99).
      The latter underwent detailed hormonal studies. LD was estimated by alternative
      Bayesian methods for inferring the extent of LD when haplotypes at different loci
      are inferred. Population differences in single nucleotide polymorphisms were
      modest, indicating the stability of both genes across populations. Using five of
      nine potentially informative loci at CYP11B sites with allele frequency greater
      than 0.1, two major contrasting haplotypes, CwtCG and TconvGTA, were found. In
      both populations the CwtCG haplotype accounted for 44% and the TconvGTA for 32%
      of subjects. Haplotype distribution did not differ between Europeans and South
      Americans (chi(2) = 2.81; P = 0.09). In vivo 11 beta-hydroxylase activity,
      estimated from urinary steroid profiling, was lower in subjects with an increased
      aldosterone to renin ratio or with the TconvGTA haplotype. These findings
      indicate that genotypes at the CYP11B locus are in strong LD and that identified
      haplotypes predict 11 beta-hydroxylase activity.

PMID- 15507510
TI  - Effects of insulin-like growth factor I and II on prostaglandin synthesis and
      plasminogen activator activity in human umbilical vein endothelial cells.
AB  - IGFs seem to contribute to the endothelial dysfunction observed in some vascular
      diseases. Because locally increased IGFs levels were detected in the preeclamptic
      fetoplacental unit, we hypothesized their involvement in the dysregulation of
      fibrinolysis and vascular tone typically observed in the fetoplacental
      compartment in this pregnancy disease. Therefore, in human umbilical vein
      endothelial cells (HUVECs), the potential effect of IGFs on the synthesis of
      plasminogen activators (PAs), PA inibitor-1 (PAI-1), and vasodilator and
      vasoconstrictor prostaglandins (PGs) was investigated. Moreover, in HUVECs
      treated with IGFs, the expression of cyclooxygenase (COX)-2, the rate-limiting
      enzyme in PG synthesis, was evaluated.HUVECs were treated for 24 h with IGFs (1
      100 ng/ml) or IL-1beta (0.1 ng/ml). PA, PAI-1, and COX-2 mRNA was determined by
      RT-PCR and PG release and PA activity by RIA and colorimetric assay,
      respectively.We demonstrated an inhibition of urokinase-type PA activity and a
      50% reduction of urokinase-type PA mRNA in HUVECs treated with IGFs. No effect
      was seen on PAI-1. Finally, both IGFs significantly decreased all PGs tested and
      COX-2 mRNA, whereas, as expected, IL-1beta had an opposite effect. In conclusion,
      our results suggest for IGFs a potential involvement in the endothelial
      dysfunction observed in preeclamptic fetoplacental unit.

PMID- 15507511
TI  - beta-Cell function: a key pathological determinant in polycystic ovary syndrome.
AB  - We report data from 60 patients with polycystic ovary syndrome (PCOS) who had
      undergone assessment of insulin resistance, pancreatic beta-cell function,
      obesity, and androgen levels to elucidate the complex relationships among these
      traits. Homeostasis model assessment was used to quantify insulin resistance and
      beta-cell function. A reference population was derived from the National Health
      and Nutrition Examination Study (NHANES III, 1988-1994). Indices of insulin
      resistance, insulin secretion, bioavailable testosterone, and body mass index all
      exhibited significant pairwise correlations. Multiple regression analysis
      clarified the phenotypic relationships, demonstrating that insulin resistance and
      bioavailable testosterone were independent predictors of beta-cell function; beta
      cell function and obesity were independent predictors of insulin resistance; and
      beta-cell function was an independent predictor of bioavailable testosterone. Of
      note, comparison with normal women from NHANES revealed a significantly stronger
      relationship between beta-cell function and insulin resistance in PCOS, raising
      the possibility of an intrinsic defect in beta-cell function whereby increasing
      insulin resistance leads to a greater insulin response in PCOS than normal. The
      altered relationship of beta-cell function and insulin resistance coupled with
      the fact that beta-cell function, not insulin resistance, was a predictor of
      hyperandrogenemia suggests that beta-cell dysfunction may be a key pathogenic
      determinant in PCOS.

PMID- 15507512
TI  - Expression of allograft inflammatory factor-1 in human eutopic endometrium and
      endometriosis: possible association with progression of endometriosis.
AB  - Allograft inflammatory factor-1 (AIF-1) is a cytokine originally identified in
      rat cardiac allografts with chronic rejection. AIF-1 is expressed in various
      human immune-related tissues and is thought to play a role in inflammatory
      responses and the immune activation and function of macrophages. Expression has
      also been shown in human placentas and bovine embryos, suggesting that AIF-1 may
      be involved in reproductive function. Immune factors are thought to be involved
      in the pathogenesis of endometriosis. High concentrations of activated
      macrophages and various cytokines have been found in the peritoneal fluid of
      patients with endometriosis. In the current work we examined the expression of
      AIF-1 in human eutopic endometrium and endometriosis, and measured AIF-1 in
      peritoneal fluid samples from women with and without endometriosis. RT-PCR,
      Western blot analysis, and immunohistochemistry showed that AIF-1 mRNA and
      protein were expressed both in eutopic endometrium and in endometriotic tissue.
      In eutopic endometrium, expression was greater in the late secretory and
      menstrual phases than in other phases of the menstrual cycle (P < 0.01). AIF-1
      protein was present in greater amounts in peritoneal fluid from patients with
      endometriosis than in women without it (P < 0.01), and its concentration
      correlated with the Revised American Society for Reproductive Medicine score (rs
      = 0.693; P < 0.0001). Peritoneal macrophages from endometriosis patients secreted
      more AIF-1 than those from unaffected women (P < 0.05). AIF-1 release from
      macrophages was stimulated by IL-1beta (P < 0.01) and interferon-gamma (P <
      0.05). These results demonstrate for the first time that AIF-1 is expressed in
      eutopic endometrium and endometriotic tissue, suggesting that AIF-1 is one
      cytokine in the local network involved in the onset of menstruation. AIF-1
      derived from peritoneal macrophages may also possibly play a significant role in
      the pathophysiology and progression of endometriosis.

PMID- 15507513
TI  - Differential regulation of estrogen receptor (ER)alpha and ERbeta in primate
      mammary gland.
AB  - Estrogen, mainly estradiol (E2), and progesterone (P) are essential for the
      growth and differentiation of the breast, but their roles in breast cancer are
      highly debated. To understand how E2 and P influence cell proliferation and
      differentiation, it is essential to know how their receptors are regulated.
      Because of limited tissue availability, little is known about regulation of the
      two estrogen receptors (ERalpha and ERbeta) and the two progesterone receptor
      isoforms (PR-A and PR-B) in the normal human breast. What we know comes from
      rodent studies, which are not always pertinent for the human breast. We report
      now on regulation of gonadal hormone receptors during the menstrual cycle,
      pregnancy, and lactation in rhesus monkey mammary gland and on the relationship
      of these receptors to proliferation. We found that ERalpha but not ERbeta is down
      regulated when E2 levels increase and when cells enter the cell cycle. PR-B but
      not PR-A is expressed in proliferating cells. Thus under normal conditions, the
      ratio of ERalpha to ERbeta in the breast depends on plasma concentrations of E2.
      Elevated expression of ERalpha (as occurs in postmenopausal women) is a normal
      response to loss of E2 and indicates nonproliferating cells. As selective
      receptor ligands become available, they will be helpful in delineation of the
      functions of these receptors.

PMID- 15507514
TI  - Activation of caspases-3, -6, and -9 during finasteride treatment of benign
      prostatic hyperplasia.
AB  - Benign prostatic hyperplasia (BPH) results from an increase in both epithelial
      and stromal compartments of the human prostate. Although inhibitors of 5alpha
      reductase such as finasteride have been shown to reduce the size of BPH tissues
      by inducing apoptosis, their mechanisms of action still remain unknown. The
      present study supports that such a process triggered by finasteride is caspase
      dependent with a possible involvement of two effector caspases (caspase-3 and 6)
      and two initiator caspases (caspase-8 and 9). Indeed, by using tissues from
      patients affected by BPH and treated by finasteride (5 mg/d) for 2-3, 6-8, or 27
      32 d, we observed that the 5alpha-reductase inhibitor induced apoptosis in
      epithelial cells (evaluated through cell number positive for terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end
      labeling) as early as 2-3 d of treatment, with a maximal activity (250-fold
      increase, P < 0.0001) at 6-8 d of treatment. However, after 27-32 d of treatment,
      the number of apoptotic cells was reduced and was close to control. Caspases-3, 
      6, -8, and -9 were immunolocalized to (basal and secretory) epithelial cells and
      to a lesser extent to stromal cells. Activated caspase-3 immunoexpression was
      restricted to epithelial secretory cells, and its immunostaining intensity
      appeared to be higher in BPH tissues from patients treated for 2-3 or 6-8 d.
      Consistently, in Western blotting analyses, activated caspases-3 and -6 were
      detected as early as 2-3 d of treatment in BPH tissues, and their levels were
      increased after 6-8 d of treatment. In real time quantitative PCR experiments,
      caspase-3 and -6 mRNA levels were found to be unchanged after finasteride
      treatment. Activated caspase-8 was not detected in the different conditions
      tested, whereas activated caspase-9 protein levels were maximally enhanced after
      2-3 d of finasteride treatment. In conclusion, we report here that finasteride
      treatment of BPH tissues induced a caspase-dependent apoptotic process restricted
      to epithelial cells by activating effector caspases-3 and -6 and exhibited a
      transient action because the apoptotic process was no longer observed after 27-32
      d of treatment.

PMID- 15507515
TI  - Colonoscopic screening and follow-up in patients with acromegaly: a multicenter
      study in Italy.
AB  - Acromegaly is an infrequent disease attributable to endogenous excess of GH and
      IGF-I. Human studies have associated the GH-IGF-I axis with the development of
      colorectal cancer; however, the question of whether colorectal cancer is a
      problem in acromegaly is currently unresolved. We performed a cross-sectional
      study to assess the risk of colonic neoplasia in patients with acromegaly.
      Colonoscopic screening was performed in 235 patients with acromegaly at five
      tertiary care hospitals in Italy between January 1, 1996, and December 31, 2001.
      A repeat colonoscopy was performed in 121 patients after a mean interval of 32.1
      months. Colonoscopic findings in patients with acromegaly were compared with
      those of 233 patients with nonspecific abdominal complaints who were referred for
      endoscopy during the study period. A total of 65 patients (27.7%) and 36 controls
      (15.5%) had colonic neoplasia. In 55 patients (23.4%) and 34 control subjects
      (14.6%), the most important findings were adenomas (odds ratio, 1.7; range, 1.1
      2.5), whereas 10 patients (4.3%) and two control subjects (0.9%) had carcinoma
      (odds ratio, 4.9; range, 1.1-22.4). The risk of colonic neoplasia was higher for
      younger patients with acromegaly compared with age-matched controls. Patients
      with acromegaly with or without colonic neoplasia did not differ significantly
      for IGF-I levels or duration of disease. A neoplastic recurrence was found in
      16.5% of patients who underwent follow-up; 90% of them had had a neoplasm removed
      at the first colonoscopy. Acromegaly carries with it a moderate, but definitive,
      increase in the risk of colonic neoplasia that occurs at a younger age than in
      the general population. Patients who are found to harbor a colonic neoplasia are
      at risk for recurrence.

PMID- 15507516
TI  - Effects of race and family history of type 2 diabetes on metabolic status of
      women with polycystic ovary syndrome.
AB  - Racial origin and family history of type 2 diabetes impact upon the risk of
      developing impaired glucose tolerance (IGT) and type 2 diabetes, both of which
      are common in women with polycystic ovary syndrome (PCOS). We examined the
      effects of race and family history of type 2 diabetes on the risk of IGT and type
      2 diabetes in a large cohort of women with PCOS. Data obtained at baseline were
      analyzed from 408 premenopausal women with PCOS. Multivariate linear regression
      models were used to assess the impact of race (white, black, and other) and
      family history of type 2 diabetes on body mass index, waist circumference, and
      waist to hip ratio; glycemic measures (glucose and insulin levels obtained during
      a standard 75-g oral glucose tolerance test, fasting glucose to insulin ratio,
      and homeostasis model assessment model of insulin resistance derived from fasting
      levels of glucose and insulin), hemoglobin A(1c), and SHBG, and
      dehydroepiandrosterone sulfate levels. Sixteen (4%) of the 408 patients had type
      2 diabetes, 94 (23%) had IGT, and the remaining 298 (73%) had normal glucose
      tolerance. A history of type 2 diabetes in either parent (FHxPOS) was present in
      seven (44%) of the 16 diabetic women with PCOS, 37 (39%) of the 94 women with
      IGT, and 62 (21%) of those with normal glucose tolerance (P < 0.01, by chi(2)
      test). The prevalences of IGT and type 2 diabetes were significantly higher in
      FHxPOS PCOS women compared with FHxNEG PCOS women, IGT evident in 37 (35%) FHxPOS
      compared with 57 (19%) FHxNEG women, and type 2 diabetes evident in seven (7%)
      FHxPOS compared with nine (3%) FHxNEG women. Among the 392 nondiabetic subjects,
      after adjustment for the effects of race, FHxPOS differed significantly from
      FHxNEG patients in having a higher mean waist to hip ratio, hemoglobin A(1c)
      level, 2-h glucose level, fasting glucose and insulin levels, glucose to insulin
      ratio, homeostasis model assessment model of insulin resistance, and areas under
      the glucose and insulin curves during the oral glucose tolerance test. A family
      history of type 2 diabetes was present with a significantly greater frequency
      among women with PCOS who had IGT or type 2 diabetes compared with those with
      normal glucose tolerance. Conversely, a family history of type 2 diabetes in a
      first-degree relative was associated with a significantly higher risk for IGT or
      type 2 diabetes in women with PCOS. Even among nondiabetic women with PCOS, a
      positive family history of type 2 diabetes was strongly associated with metabolic
      characteristics associated with an increased risk for type 2 diabetes. Finally,
      the fasting glucose concentration was poorly associated with 2-h glucose
      concentrations among PCOS women with IGT, suggesting that the fasting glucose
      concentration is inadequate to predict the presence of IGT in PCOS.

PMID- 15507517
TI  - Cytochromes 1A1/1B1- and catechol-O-methyltransferase-derived metabolites mediate
      estradiol-induced antimitogenesis in human cardiac fibroblast.
AB  - We investigated the role of specific cytochrome P450s (CYP450s) and catechol-O
      methyltransferase (COMT) in the growth inhibitory effects of estradiol in cardiac
      fibroblasts (CFs) expressing functional estrogen receptors. 3
      Methylcholantherene, phenobarbital (broad-spectrum CYP450 inducers), and beta
      naphthoflavone (CYP1A1/1A2 inducer) augmented, and 1-aminobenzotriazole (broad
      spectrum CYP450 inhibitor) blocked, the inhibitory effects of estradiol on serum
      induced CF growth (DNA synthesis, cell number, and collagen synthesis). Neither
      ketoconazole (3A4 inhibitor) nor furafylline (selective 1A2 inhibitor) altered
      the antimitogenic effects of estradiol on CF growth. In contrast, ellipticine
      (selective 1A1 inhibitor), pyrene (selective 1B1 inhibitor), and alpha
      naphthoflavone (1A1>1A2 inhibitor) abrogated the antimitogenic effects of
      estradiol on CF growth. OR486 (COMT inhibitor) also blocked the antimitogenic
      effects of estradiol in both the presence and absence of the CYP450 inducers.
      ICI182780 (estrogen receptor antagonist) attenuated the growth inhibitory effects
      of estradiol, but only at concentrations that inhibit the metabolism of estradiol
      to hydroxyestradiols (precursors of methoxyestradiols). CFs expressed CYP1A1 and
      CYP1B1, isozymes that convert estradiol to hydroxyestradiols. Moreover, CFs
      metabolized estradiol to hydroxyestradiol, and 2-hydroxyestradiol to 2
      methoxyestradiol. OR486 and quercetin (COMT inhibitor) blocked the conversion of
      2-hydroxyestradiol to 2-methoxyestradiol in CFs. We conclude that the
      antimitogenic effects of estradiol on CF growth are mediated in part by
      conversion to hydroxyestradiols via CYP1A1 and CYP1B1, followed by metabolism of
      hydroxyestradiols to methoxyestradiols by COMT.

PMID- 15507518
TI  - Effects of changes in body weight and insulin resistance on inflammation and
      endothelial function in morbid obesity after bariatric surgery.
AB  - Metabolic alterations such as insulin resistance are thought to underlie the
      endothelial dysfunction and low grade inflammation found in morbid obesity.
      Twenty-six morbidly obese patients, aged 39.0 +/- 10.0 (mean +/- sd), were
      evaluated before and 4.2 +/- 0.8 months after bariatric surgery. A marked
      increment in the insulin sensitivity index (S(I)) and the endothelium-dependent
      vasodilatory response in a dorsal hand vein was observed after weight loss
      following bariatric surgery. Circulating levels of E-selectin, P-selectin,
      plasminogen activator inhibitor-1, and von Willebrand factor, which were higher
      than those in the control group, decreased significantly after surgery. Plasma
      vascular cell adhesion molecule-1, angiotensin-converting enzyme, intercellular
      adhesion molecule-1, thrombomodulin, and plasma and intraplatelet cGMP levels did
      not change after weight loss. All inflammatory markers were higher in morbidly
      obese patients. After surgery, C- reactive protein and sialic acid diminished,
      whereas circulating levels of IL-6, TNF-alpha, and its soluble receptors did not.
      Positive correlations were found between changes in adiposity and S(I) and
      changes in C-reactive protein and between changes in sialic acid and changes in
      endothelial function. In conclusion, a marked improvement in S(I), endothelial
      function, and low grade inflammation was observed in the weight-losing, morbidly
      obese patients after bariatric surgery. S(I) and adiposity appear to play roles
      in obesity-related, low grade inflammation that contribute to the endothelial
      dysfunction observed in morbid obesity.

PMID- 15507519
TI  - Altered specificity of Hint-W123Q supports a role for Hint inhibition by ASW in
      avian sex determination.
AB  - Hint is a universally conserved, dimeric AMP-lysine hydrolase encoded on the
      avian Z chromosome. Tandemly repeated on the female-specific W chromosome, Asw
      encodes a potentially sex-determining, dominant-negative Hint dimerization
      partner whose substrate-interacting residues were specifically altered in
      evolution. To test the hypothesis that Gln127 of Asw is responsible for
      depression and/or alteration of Hint enzyme activity, a corresponding mutant was
      created in the chicken Hint homodimer, and a novel substrate was developed that
      links reversal of AMP-lysine modification to aminomethylcoumarin release.
      Strikingly, the Hint-W123Q substitution reduced k(cat)/K(m) for AMP-lysine
      hydrolysis 17-fold, while it increased specificity for AMP-para-nitroaniline
      hydrolysis by 160-fold. The resulting 2,700-fold switch in enzyme specificity
      suggests that Gln127 could be the dominant component of Asw dominant negativity
      in avian feminization.

PMID- 15507520
TI  - Identification of MEF2-regulated genes during muscle differentiation.
AB  - Although a great deal has been elucidated concerning the mechanisms regulating
      muscle differentiation, little is known about transcription factor-specific gene
      regulation. Our understanding of the genetic mechanisms regulating cell
      differentiation is quite limited. Much of what has been defined centers on
      regulatory signaling cascades and transcription factors. Surprisingly few studies
      have investigated the association of genes with specific transcription factors.
      To address these issues, we have utilized a method coupling chromatin
      immunoprecipitation and CpG microarrays to characterize the genes associated with
      MEF2 in differentiating C(2)C(12) cells. Results demonstrated a defined binding
      pattern over the course of differentiation. Filtered data demonstrated 9 clones
      to be elevated at 0 h, 792 at 6 h, 163 by 1 day, and 316 at 3 days. Using
      unbiased selection parameters, we selected a subset of 291 prospective
      candidates. Clones were sequenced and filtered for removal of redundancy between
      clones and for the presence of repetitive elements. We were able to place 50 of
      these on the mouse genome, and 20 were found to be located near well-annotated
      genes. From this list, previously undefined associations with MEF2 were
      discovered. Many of these genes represent proteins involved in neurogenesis,
      neuromuscular junctions, signaling and metabolism. The remaining clones include
      many full-length cDNA and represent novel gene targets. The results of this study
      provides for the first time, a unique look at gene regulation at the level of
      transcription factor binding in differentiating muscle.

PMID- 15507521
TI  - Gfi-1B plays a critical role in terminal differentiation of normal and
      transformed erythroid progenitor cells.
AB  - Growth factor independence-1B (Gfi-1B) is a transcription factor with a highly
      conserved transcriptional repressor snail-Gfi-1 (SNAG) domain and 6 zinc-finger
      domains at the N- and C-terminus, respectively. Disruption of the Gfi-1B gene is
      lethal in the embryo with failure to produce definitive enucleated erythrocytes.
      In this study, we analyzed the role of Gfi-1B in human erythropoiesis. We
      observed an increase of Gfi-1B expression during erythroid maturation of human
      primary progenitor cells. We studied the consequences of variations in Gfi-1B
      expression in 2 transformed cell lines (K562 and UT7 cells), as well as in
      primary CD36(+)/GPA(-) progenitors. A knock-down of Gfi-1B delayed the terminal
      differentiation of K562 and primary cells. Forced expression of Gfi-1B in UT7 and
      K562 cells led to an arrest of proliferation and an induction of erythroid
      differentiation. Enforced expression of Gfi-1B in primary cells at the colony
      forming units-erythroid (CFU-E) stage led to a partial glycophorin A (GPA)
      induction after erythropoietin (EPO) withdrawal but failed to protect cells from
      apoptosis. Deletion of the SNAG repressor domain abolished Gfi-1B-induced
      erythroid maturation, strongly suggesting that Gfi-1B acts in the late stage of
      erythroid differentiation as a transcriptional repressor.

PMID- 15507522
TI  - Selective cytotoxicity and telomere damage in leukemia cells using the telomerase
      inhibitor BIBR1532.
AB  - Telomerase represents an attractive target for a mechanism-based therapeutic
      approach because its activation has been associated with unlimited proliferation
      in most cancer cells. Recently, a nonnucleosidic small molecule inhibitor,
      BIBR1532 (2-[(E)-3-naphtalen-2-yl-but-2-enoylamino]-benzoic acid), has been
      identified that is highly selective for inhibition of telomerase, resulting in
      delayed growth arrest of tumor cells. Here we examined the effects of BIBR1532 in
      different leukemia cell lines as well as in primary cells from patients with
      acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) in short-term
      culture assays. We observed a dose-dependent direct cytotoxicity in
      concentrations ranging from 30 to 80 microM. Interestingly, cell death was not
      dependent on the catalytic activity of telomerase but was delayed in cells with
      very long telomeres. We observed time-dependent individual telomere erosion,
      which was associated with loss of telomeric repeat binding factor 2 (TRF2) and
      increased phosphorylation of p53. Importantly, the proliferative capacity of
      normal CD34(+) cells from cord blood and leukapheresis samples was not affected
      by treatment with BIBR1532. We conclude that using this class of telomerase
      inhibitor at higher concentrations exerts a direct cytotoxic effect on malignant
      cells of the hematopoietic system, which appears to derive from direct damage of
      the structure of individual telomeres and must be dissected from telomerase
      suppressed overall telomere shortening.

PMID- 15507523
TI  - Generation of migratory antigen-specific plasma blasts and mobilization of
      resident plasma cells in a secondary immune response.
AB  - Maintenance of protective humoral immunity depends on the generation and survival
      of antibody-secreting cells. The bone marrow provides niches for long-term
      survival of plasma cells generated in the course of systemic immune responses in
      secondary lymphoid organs. Here, we have analyzed migratory human plasma blasts
      and plasma cells after secondary vaccination with tetanus toxin. On days 6 and 7
      after immunization, CD19(+)/CD27(high)/intracellular immunoglobulin G(high)
      (IgG(high))/HLA-DR(high)/CD38(high)/CD20(-)/CD95(+) tetanus toxin-specific
      antibody-secreting plasma blasts were released in large numbers from the
      secondary lymphoid organs into the blood. These cells show chemotactic
      responsiveness toward ligands for CXCR3 and CXCR4, probably guiding them to the
      bone marrow or inflamed tissue. At the same time, a population of
      CD19(+)/CD27(high)/intracellular IgG(high)/HLA-DR(low)/CD38(+)/CD20(-)/CD95(+)
      cells appeared in the blood in large numbers. These cells, with the phenotype of
      long-lived plasma cells, secreted antibodies of unknown specificity, not tetanus
      toxoid. The appearance of these plasma cells in the blood indicates successful
      competition for survival niches in the bone marrow between newly generated plasma
      blasts and resident plasma cells as a fundamental mechanism for the establishment
      of humoral memory and its plasticity.

PMID- 15507524
TI  - Relative antithrombotic effect of soluble GPVI dimer compared with anti-GPVI
      antibodies in mice.
AB  - Glycoprotein VI (GPVI) is an essential platelet collagen receptor; therefore, the
      inhibition of GPVI-collagen interactions may be an attractive antithrombotic
      strategy. We have previously shown that targeting of GPVI with antibodies leads
      to the depletion of the receptor and to long-term antithrombotic protection in
      mice. An alternative agent to interfere with GPVI-collagen interactions might be
      soluble GPVI acting as a competitive inhibitor, thereby averting undesired
      effects on platelets. To test this, we expressed soluble dimeric human GPVI,
      comprising the extracellular domain of the receptor fused to the human
      immunoglobulin Fc domain (GPVI-Fc), and compared its antithrombotic potential
      with that of anti-GPVI antibodies in mice. In contrast to a recent report, we
      found by intravital fluorescence microscopy and ultrasonic flow measurements that
      GPVI-Fc had no effect on platelet adhesion and thrombus formation at the injured
      arterial wall, whereas anti-GPVI antibodies profoundly inhibited these processes.
      Similar results were obtained with a fusion protein comprising the extracellular
      domain of mouse GPVI and human IgG-Fc. This indicates that direct targeting of
      GPVI provides significantly stronger protection against arterial thrombosis than
      soluble GPVI dimer.

PMID- 15507525
TI  - Inhibition of vascular endothelial growth factor receptor 2-mediated endothelial
      cell activation by Axl tyrosine kinase receptor.
AB  - GAS6, the product of a growth arrest specific (GAS) gene, is the ligand of the
      tyrosine kinase receptor Axl. GAS6 and Axl are both expressed in endothelial
      cells, where they are involved in many processes such as leukocyte transmigration
      through capillaries and neointima formation in injured vessels. Here, we show
      that Axl stimulation by GAS6 results in inhibition of the ligand-dependent
      activation of vascular endothelial growth factor (VEGF) receptor 2 and the
      consequent activation of an angiogenic program in vascular endothelial cells.
      GAS6 inhibits chemotaxis of endothelial cells stimulated by VEGF-A isoforms, but
      not that triggered by fibroblast growth factor-2 or hepatocyte growth factor.
      Furthermore, it inhibits endothelial cell morphogenesis on Matrigel and VEGF-A
      dependent vascularization of chick chorion allantoid membrane. GAS6 activates the
      tyrosine phosphatase SHP-2 (SH2 domain-containing tyrosine phosphatase 2), which
      is instrumental in the negative feedback exerted by Axl on VEGF-A activities. A
      dominant-negative SHP-2 mutant, in which Cys 459 is substituted by Ser, reverted
      the effect of GAS6 on stimulation of VEGF receptor 2 and endothelial chemotaxis
      triggered by VEGF-A. These studies provide the first demonstration of a cross
      talk between Axl and VEGF receptor 2 and add new information on the regulation of
      VEGF-A activities during tissue vascularization.

PMID- 15507526
TI  - Enhanced antilymphoma efficacy of CD19-redirected influenza MP1-specific CTLs by
      cotransfer of T cells modified to present influenza MP1.
AB  - To enhance the in vivo antitumor activity of adoptively transferred, CD19
      specific chimeric antigen receptor (CAR)-redirected cytotoxic T lymphocytes
      (CTLs), we studied the effect of restimulating CAR(+) CTLs through their
      endogenous virus-specific T-cell antigen receptor (TcR) by the cotransfer of
      engineered T-cell antigen-presenting cells (T-APCs). Using influenza A matrix
      protein 1 (MP1) as a model antigen, we show that ex vivo-expanded CD4(+) and
      CD8(+) T-APCs expressing a hygromycin phosphotransferase-MP1 fusion protein
      (HyMP1) process and present MP1 to autologous human leukocyte antigen (HLA)
      restricted, MP1-specific CD4(+) and CD8(+) CTL precursors. The MP1-specific CTLs
      are amenable to subsequent genetic modification to express a CD19-specific CAR,
      designated CD19R, and acquire HLA-unrestricted reactivity toward CD19(+) leukemia
      and lymphoma tumor targets while maintaining HLA-restricted MP1 specificity. The
      restimulation of MP1xCD19 dual-specific CTLs in vivo by the adoptive transfer of
      irradiated HyMP1(+) T-APCs resulted in the enhanced antilymphoma potency of
      bispecific effector cells, as measured by elimination of the biophotonic signal
      of established firefly luciferase-expressing Burkitt lymphoma xenografts in
      nonobese diabetic/severe combined immunodeficiency (NOD/scid) animals compared
      with control groups restimulated by Hy(+)MP1(neg) T-APCs. Engineered T-APCs are a
      novel and versatile antigen-delivery system for generating antigen-specific T
      cells in vitro and enhancing the in vivo effector functioning of CAR-redirected
      antitumor effector cells.

PMID- 15507527
TI  - Long-term pharmacologically regulated expression of erythropoietin in primates
      following AAV-mediated gene transfer.
AB  - Gene therapy is a potential route for the delivery of secreted therapeutic
      proteins, but pharmacologic control of expression will generally be required for
      optimal safety and efficacy. Previous attempts to achieve regulated expression in
      large animal models have been thwarted by transient expression or immune
      responses to regulatory proteins. We evaluated the ability of the dimerizer
      regulated gene expression system to achieve controlled, long-term production of
      erythropoietin (Epo) following intramuscular administration of adeno-associated
      virus (AAV) vectors to 16 primates. All animals showed dose-responsive and
      completely reversible elevation of Epo and hematocrit in response to the
      dimerizer rapamycin, or analogs with reduced immunosuppressive activity,
      administered intravenously or orally. Animals that received optimized dual
      vectors showed persistent regulated expression for the duration of the study,
      with no apparent immune response to Epo or the regulatory proteins. Similar
      results were obtained with single vectors incorporating both the Epo and
      regulatory genes, including those packaged into serotype 1 AAV vectors to allow
      use of lower viral doses. For the longest-studied animal, regulated expression
      has persisted for more than 6 years and 26 induction cycles. These data indicate
      that one-time or infrequent gene transfer followed by dimerizer regulation is a
      promising approach for delivery of therapeutic proteins.

PMID- 15507528
TI  - PSK and Trx80 inhibit B-cell growth in EBV-infected cord blood mononuclear cells
      through T cells activated by the monocyte products IL-15 and IL-12.
AB  - Epstein-Barr virus (EBV)-specific immunologic memory is not transferred from
      mother to child. In vitro infection of cord blood cells can therefore readily
      lead to the outgrowth of transformed B lymphocytes. We found that the
      immunomodulator polysaccharide K (PSK) or the mitogenic cytokine truncated
      thioredoxin (Trx80) inhibited the EBV-induced B-cell proliferation. Using
      signaling lymphocytic activation molecule (SLAM)-associated protein (SAP)
      induction as a sign for T- and natural killer (NK) cell activation, we could
      follow it without any need for cell separation because neither macrophages nor B
      lymphocytes express SAP. The results suggest the following scenario: EBV infected
      and activated B lymphocytes. Upon interacting with these cells, T cells became
      posed for responding to cytokines produced by monocytes. Both PSK and Trx80,
      which is a secreted C-terminally truncated thioredoxin, activated the monocytes,
      which then produced cytokines in the presence of the primed T cells. PSK induced
      interleukin-15 (IL-15), while Trx80 induced IL-12 production. Both cytokines
      activated the T cells for function. Phosphatidylinositol 3-(PI 3)-kinase and
      reactive oxygen species (ROSs) were involved in the PSK-induced activation of
      monocytes. Restimulation of the cultures with EBV-transformed B cells generated
      specific cytotoxic activity.

PMID- 15507529
TI  - IgG antibodies that recognize epitope Gly40-Arg43 in domain I of beta 2
      glycoprotein I cause LAC, and their presence correlates strongly with thrombosis.
AB  - Anti-beta(2)-glycoprotein I antibodies are known to have a heterogeneous
      reactivity against beta(2)-glycoprotein I. We performed this study to
      characterize the epitope on beta(2)-glycoprotein I to which pathologic anti
      beta(2)-glycoprotein I antibodies are directed. Plasma samples from 198 patients
      with various systemic autoimmune diseases were tested for the presence of lupus
      anticoagulant and anti-beta(2)-glycoprotein I immunoglobulin G (IgG) antibodies.
      The reactivity of the anti-beta(2)-glycoprotein I-positive samples was further
      tested by coating recombinant full-length beta(2)-glycoprotein I and 8 deletion
      mutants of beta(2)-glycoprotein I onto hydrophilic and hydrophobic enzyme-linked
      immunosorbent assay (ELISA) plates. Full-length beta(2)-glycoprotein I with point
      mutations in domain I at positions 8, 40, and 43 were used in inhibition
      experiments. Fifty-two patients with anti-beta(2)-glycoprotein I IgG antibodies
      could be divided into 2 patterns. Type A antibodies only recognize domain I when
      coated onto hydrophobic plates; they do not recognize domain I coated onto
      hydrophilic plates. Type B antibodies have heterogeneous reactivity for all
      domains. Type A antibodies recognize the epitope around amino acids Gly40-Arg43
      and cause lupus anticoagulant activity. In contrast to type B antibodies, those
      of type A strongly correlated with thrombosis. In conclusion, antibodies directed
      at domain I (epitope comprising Gly40 and Arg43) have lupus anticoagulant
      activity and strongly associate with thrombosis.

PMID- 15507531
TI  - Enhanced rat beta-cell proliferation in 60% pancreatectomized islets by increased
      glucose metabolic flux through pyruvate carboxylase pathway.
AB  - Islet beta-cell proliferation is a very important component of beta-cell
      adaptation to insulin resistance and prevention of type 2 diabetes mellitus.
      However, we know little about the mechanisms of beta-cell proliferation. We now
      investigate the relationship between pyruvate carboxylase (PC) pathway activity
      and islet cell proliferation 5 days after 60% pancreatectomy (Px). Islet cell
      number, protein, and DNA content, indicators of beta-cell proliferation, were
      increased two- to threefold 5 days after Px. PC and pyruvate dehydrogenase (PDH)
      activities increased only approximately 1.3-fold; however, islet pyruvate content
      and malate release from isolated islet mitochondria were approximately threefold
      increased in Px islets. The latter is an indicator of pyruvate-malate cycle
      activity, indicating that most of the increased pyruvate was converted to
      oxaloacetate (OAA) through the PC pathway. The contents of OAA and malate,
      intermediates of the pyruvate-malate cycle, were also increased threefold. PDH
      and citrate content were only slightly increased. Importantly, the changes in
      cell proliferation parameters, glucose utilization, and oxidation and malate
      release were partially blocked by in vivo treatment with the PC inhibitor
      phenylacetic acid. Our results suggest that enhanced PC pathway in Px islets may
      have an important role in islet cell proliferation.

PMID- 15507530
TI  - BCL-6 negatively regulates macrophage proliferation by suppressing autocrine IL-6
      production.
AB  - The transcription repressor BCL-6 is known to play critical roles in B-cell
      lymphomagenesis, germinal center formation, and balanced Th1/Th2 differentiation.
      In macrophages, although BCL-6 has also been shown to regulate the expression of
      several chemokine genes, its function in other aspects of macrophage biology has
      not been studied. In addition, the precise role of BCL-6 in cell proliferation is
      poorly understood in general. Here we report that BCL-6(-/-) macrophages
      hyperproliferate due to an accelerated G(1)/S transition accompanied by increased
      cyclin D2 and c-myc and decreased expression of p27. Crucial to this enhanced
      proliferation is spontaneous interleukin 6 (IL-6) production and signal
      transducer and activator of transcription 3 (STAT3) activation in BCL-6(-/-)
      macrophages. In colony-forming assays, BCL- 6(-/-) bone marrow progenitor cells
      form spontaneous macrophage colonies that can be inhibited by anti-IL-6
      antibodies. Gene expression studies demonstrate that BCL-6 binds to several
      sequence motifs scattered in the IL-6 locus and can repress IL-6 transcription
      both in 293T cells and in macrophages. In conclusion, our results indicate that
      BCL-6 negatively regulates proliferation of the monocytic/macrophage lineage by
      suppressing an autocrine IL-6/STAT3-mediated gene expression program. Our work
      also suggests that BCL-6 prevents abnormal Th2 differentiation by suppressing
      basal level IL-6 production in antigen-presenting cells (APCs).

PMID- 15507532
TI  - Human soleus and vastus lateralis muscle protein metabolism with an amino acid
      infusion.
AB  - The calf muscles, compared with the thigh, are less responsive to resistance
      exercise in ambulatory and bed-rested individuals, apparently due to muscle
      specific differences in protein metabolism. We chose to evaluate the efficacy of
      using amino acids to elevate protein synthesis in the soleus, because amino acids
      have been shown to have a potent anabolic effect in the vastus lateralis. Mixed
      muscle protein synthesis in the soleus and vastus lateralis was measured before
      and after infusion of mixed amino acids in 10 individuals (28 +/- 1 yr).
      Phosphorylation of ribosomal protein p70 S6 kinase (p70S6K; Thr389) and
      eukaryotic initiation factor 4E-binding protein-1 (4E-BP1; Thr37/46) was also
      evaluated at rest and after 3 h of amino acid infusion. Basal protein synthesis
      was similar (P = 0.126), and amino acids stimulated protein synthesis to a
      similar extent (P = 0.004) in the vastus lateralis (0.043 +/- 0.011%/h) and
      soleus (0.032 +/- 0.017%/h). Phosphorylation of p70S6K (P = 0.443) and 4E-BP1 (P
      = 0.192) was not increased in either muscle; however, the soleus contained more
      total (P = 0.002) and phosphorylated (P = 0.013) 4E-BP1 than the vastus
      lateralis. These data support the need for further study of amino acid
      supplementation as a means to compensate for the reduced effectiveness of calf
      resistance exercise in ambulatory individuals and those exposed to extended
      periods of unloading. The greater 4E-BP1 in the soleus suggests that there is a
      muscle-specific distribution of general translational initiation machinery in
      human skeletal muscle.

PMID- 15507533
TI  - PKC-delta-dependent activation of oxidative stress in adipocytes of obese and
      insulin-resistant mice: role for NADPH oxidase.
AB  - Oxidative stress is thought to be one of the causative factors contributing to
      insulin resistance and type 2 diabetes. Previously, we showed that reactive
      oxygen species (ROS) production is significantly increased in adipocytes from
      high-fat diet-induced obese and insulin-resistant mice (HF). ROS production was
      also associated with the increased activity of PKC-delta. In the present studies,
      we hypothesized that PKC-delta contributes to ROS generation and determined their
      intracellular source. NADPH oxidase inhibitor diphenyleneiodonium chloride (DPI)
      reduced ROS levels by 50% in HF adipocytes, and inhibitors of NO synthase (L
      NAME, 1 mM), xanthine oxidase (allopurinol, 100 microM), AGE formation
      (aminoguanidine, 10 microM), or the mitochondrial uncoupler (FCCP, 10 microM) had
      no effect. Rottlerin, a selective PKC-delta inhibitor, suppressed ROS levels by
      approximately 50%. However, neither GO-6976 nor LY-333531, effective inhibitors
      toward conventional PKC or PKC-beta, respectively, significantly altered ROS
      levels in HF adipocytes. Subsequently, adenoviral-mediated expression of wild
      type PKC-delta or its dominant negative mutant (DN-PKC-delta) in HF adipocytes
      resulted in either a twofold increase in ROS levels or their suppression by 20%,
      respectively. In addition, both ROS levels and PKC-delta activity were sharply
      reduced by glucose depletion. Taken together, these results suggest that PKC
      delta is responsible for elevated intracellular ROS production in HF adipocytes,
      and this is mediated by high glucose and NADPH oxidase.

PMID- 15507534
TI  - Isotope tracer measures of meal fatty acid metabolism: reproducibility and
      effects of the menstrual cycle.
AB  - Oxidation and adipose tissue uptake of dietary fat can be measured by adding
      fatty acid tracers to meals. These studies were conducted to measure between
      study variability of these types of experiments and assess whether dietary fatty
      acids are handled differently in the follicular vs. luteal phase of the menstrual
      cycle. Healthy normal-weight men (n = 12) and women (n = 12) participated in
      these studies, which were block randomized to control for study order, isotope
      ([3H]triolein vs. [14C]triolein), and menstrual cycle. Energy expenditure
      (indirect calorimetry), meal fatty acid oxidation, and meal fatty acid uptake
      into upper body and lower body subcutaneous fat (biopsies) 24 h after the
      experimental meal were measured. A greater portion of meal fatty acids was stored
      in upper body subcutaneous adipose tissue (24 +/- 2 vs. 16 +/- 2%, P < 0.005) and
      lower body fat (12 +/- 1 vs. 7 +/- 1%, P < 0.005) in women than in men. Meal
      fatty acid oxidation (3H2O generation) was greater in men than in women (52 +/- 3
      vs. 45 +/- 2%, P = 0.04). Leg adipose tissue uptake of meal fatty acids was 15 +/
      2% in the follicular phase of the menstrual cycle and 10 +/- 1% in the luteal
      phase (P = NS). Variance in meal fatty acid uptake was somewhat (P = NS) greater
      in women than in men, although menstrual cycle factors did not contribute
      significantly. We conclude that leg uptake of dietary fat is slightly more
      variable in women than in men, but that there are no major effects of menstrual
      cycle on meal fatty acid disposal.

PMID- 15507535
TI  - Postprandial intestinal and whole body nitrogen kinetics and distribution in
      piglets fed a single meal.
AB  - Our aim was to characterize the postprandial total and dietary N fluxes in the
      portal drained viscera (PDV) and whole body after administration of a single meal
      in young pigs. Seven 4-wk-old piglets, implanted with a portal flow probe and
      portal, arterial and venous catheters, received a primed constant [(18)O]urea
      intravenous infusion and were studied for 8 h after a bolus mixed meal ingestion
      (46 mmol N/kg body wt) intrinsically labeled with (15)N to trace dietary N
      fluxes. The real cecal digestibility of the formula was 94.3% (SD 1.8). PDV
      output of dietary N was found principally in the pool of circulating protein (51%
      of the measured dietary N PDV output), in the free alpha-amino N pool (44%), and
      to a lesser extent in ammonia (5%). Dietary N release in alpha-amino N and
      ammonia mainly occurred during the first 3 h. Total and exogenous postprandial
      urea productions were 5.8 and 2.0 mmol N/kg body wt, respectively. At the end of
      the postprandial period, losses of dietary N amounted to 10.3% of the dose: 5.7%
      through ileal losses and 4.6% by deamination and transfer to urea. Net
      postprandial retention of dietary N was 90.4% (SD 1.3), of which 20% was found in
      splanchnic zone (small intestine 10%, liver 5%, and plasma protein 3%) and 42% in
      peripheral zone (muscle 31%, skin 6%). In conclusion, our results show a high
      efficiency of dietary N utilization for muscular uptake and anabolic utilization.
      However, the results obtained point out the necessity to further explore the form
      of dietary N released into the portal blood.

PMID- 15507536
TI  - Thermodynamic-based computational profiling of cellular regulatory control in
      hepatocyte metabolism.
AB  - Thermodynamic-based constraints on biochemical fluxes and concentrations are
      applied in concert with mass balance of fluxes in glycogenesis and glycogenolysis
      in a model of hepatic cell metabolism. Constraint-based modeling methods that
      facilitate predictions of reactant concentrations, reaction potentials, and
      enzyme activities are introduced to identify putative regulatory and control
      sites in biological networks by computing the minimal control scheme necessary to
      switch between metabolic modes. Computational predictions of control sites in
      glycogenic and glycogenolytic operational modes in the hepatocyte network compare
      favorably with known regulatory mechanisms. The developed hepatic metabolic model
      is used to computationally analyze the impairment of glucose production in von
      Gierke's and Hers' diseases, two metabolic diseases impacting glycogen
      metabolism. The computational methodology introduced here can be generalized to
      identify downstream targets of agonists, to systematically probe possible drug
      targets, and to predict the effects of specific inhibitors (or activators) on
      integrated network function.

PMID- 15507537
TI  - Skeletal muscle protein mobilization during the progression of lactation.
AB  - To investigate changes in muscle metabolism during lactation, serial biopsy of
      the triceps brachii was conducted in first-parity sows subjected to three degrees
      of selective protein mobilization through restriction of dietary protein intake
      (see Clowes EJ, Aherne FX, Foxcroft GR, and Baracos VE. J Anim Sci 81: 753-764,
      2003). Muscle biopsies were taken 7 days before parturition and at 12 and 23 days
      of lactation. The following changes occurred after parturition, were progressive,
      and were significantly magnified in animals under the greatest degree of dietary
      protein restriction and hence of protein mobilization. Decreased RNA-to-DNA ratio
      (capacity for protein synthesis) was observed. The presence of increased
      expression of several elements of the ubiquitin proteasome proteolytic pathway
      suggested a robust catabolic response. However, as lactation progressed, and
      especially under conditions of increased dietary protein restriction, protein
      mobilization increased, muscle RNA-to-DNA ratio fell further, protease gene
      expression continued to rise, tissue free glutamine levels rose dramatically, and
      essential amino acid levels, especially branched-chain amino acids and threonine,
      fell to below prepartum levels.

PMID- 15507540
TI  - Metabolism of 26,26,26,27,27,27-F6-1 alpha,23S,25-trihydroxyvitamin D3 by human
      UDP-glucuronosyltransferase 1A3.
AB  - 26,26,26,27,27,27-Hexafluoro-1alpha,25-dihydroxyvitamin D(3) [F(6)-1alpha,
      25(OH)(2)D(3)], which is now clinically used as a drug for secondary
      hyperparathyroidism, is a hexafluorinated analog of the active form of vitamin
      D(3). Our previous studies demonstrated that CYP24A1 is responsible for the
      metabolism of F(6)-1alpha,25(OH)(2)D(3) in the target tissues and that F(6)
      1alpha,25(OH)(2)D(3) was successively converted to F(6)-1alpha,23S,25(OH)(3)D(3)
      and F(6)-23-oxo-1alpha,25(OH)(2)D(3). In this study, we examined the metabolism
      of F(6)-1alpha,25(OH)(2)D(3),F(6)-1alpha,23S,25(OH)(3)D(3), and F(6)-23-oxo
      1alpha,25(OH)(2)D(3) by human UDP-glucuronosyltransferases (UGTs). Of these
      compounds, F(6)-1alpha,23S,25(OH)(3)D(3) was remarkably glucuronidated both in
      human liver microsomes and in the recombinant system expressing human UGT. No
      significant interindividual differences were observed among 10 human liver
      samples. The recombinant system for 12 species of human UGTs revealed that F(6)
      1alpha,23S,25(OH)(3)D(3) glucuronidation was specifically catalyzed by UGT1A3.
      The information obtained in this study seems very useful to predict the
      metabolism and efficacy of vitamin D analogs in human bodies before clinical
      trials. In addition, note that for the first time a possible probe substrate for
      UGT1A3 has been found.

PMID- 15507541
TI  - Functional analysis of dog multidrug resistance-associated protein 2 (Mrp2) in
      comparison with rat Mrp2.
AB  - We investigated whether the species difference in the biliary excretion activity
      of some Mrp2 substrates was attributable to the intrinsic transport potential or
      the expression level of Mrp2, especially in rat and dog. Dog Mrp2 cDNA was
      isolated from beagle dog liver, and a vesicle transport study was performed using
      recombinant rat and dog Mrp2 expressed in insect Sf9 cells. The ATP-dependent
      transport of 17beta-estradiol 17-(beta-D-glucuronide) ([3H]E(2)17betaG) and
      leukotriene C4 ([3H]LTC4), normalized by the absolute protein expression level,
      was similar in both Mrp2s. The Mrp2 protein expression in dog liver was only 10%
      of that in rat liver and was comparable with the reported difference in the
      biliary excretion clearance of temocaprilat as Mrp2 substrate. In contrast to
      LTC4, unique transport kinetics for E(2)17betaG were evident in dog Mrp2. In
      addition to the high-affinity site with a K(m) value of 3.25 +/- 0.10 microM,
      which is similar to that in rat Mrp2 (4.81 +/- 1.21 microM), dog Mrp2 has an
      additional low-affinity site (>>75 microM), which makes a major contribution to
      the transport of E(2)17betaG (65% of the total transport capacity at tracer
      concentration). In summary, the difference in the biliary excretion activity of
      Mrp2 substrates between rat and dog depends on the Mrp2 protein expression level
      rather than the intrinsic transport activity of the transporter molecules. The
      unique transport properties of glucuronide conjugates by dog Mrp2 may lead to the
      species difference involving the drug-drug interaction or drug-induced
      hyperbilirubinemia on the bile canalicular membrane.

PMID- 15507538
TI  - Anti-inflammatory effect of the ghrelin agonist growth hormone-releasing peptide
      2 (GHRP-2) in arthritic rats.
AB  - Chronic arthritis induces hypermetabolism and cachexia. Ghrelin is a
      gastrointestinal hormone that has been proposed as a treatment to prevent
      cachexia. The aim of this work was to examine the effect of administration of the
      ghrelin agonist growth hormone-releasing peptide-2 (GHRP-2) to arthritic rats.
      Male Wistar rats were injected with Freund's adjuvant, and 15 days later
      arthritic and control rats were daily injected with GHRP-2 (100 microg/kg) or
      with saline for 8 days. Arthritis induced an increase in serum ghrelin (P < 0.01)
      and a decrease in serum concentrations of leptin (P < 0.01), whereas GHRP-2
      administration increased serum concentrations of leptin. GHRP-2 increased food
      intake in control rats but not in arthritic rats. However, in arthritic rats GHRP
      2 administration ameliorated the external symptoms of arthritis, as it decreased
      the arthritis score (10.4 +/- 0.8 vs. 13.42 +/- 0.47, P < 0.01) and the paw
      volume. In addition, circulating IL-6 and nitrites/nitrates were increased by
      arthritis, and GHRP-2 treatment decreased the serum IL-6 levels (P < 0.01). To
      elucidate whether GHRP-2 is able to modulate IL-6 release directly on immune
      cells, peritoneal macrophage cultures were incubated with GHRP-2 or ghrelin, the
      endogenous ligand of the growth hormone (GH) secretagogue receptor. Both GHRP-2
      (10(-7) M) and ghrelin (10(-7) M) prevented endotoxin-induced IL-6 and decreased
      nitrite/nitrate release from peritoneal macrophages in vitro. These data suggest
      that GHRP-2 administration has an anti-inflammatory effect in arthritic rats that
      seems to be mediated by ghrelin receptors directly on immune cells.

PMID- 15507542
TI  - Cyp2D6 catalyzes 5-hydroxylation of 1-(2-pyrimidinyl)-piperazine, an active
      metabolite of several psychoactive drugs, in human liver microsomes.
AB  - 1-(2-Pyrimidinyl)-piperazine (1-PP) is an active metabolite of several
      psychoactive drugs including buspirone. 1-PP is also the major metabolite in the
      human circulation and in rat brains following oral administration of buspirone.
      This study was conducted to identify the enzyme responsible for the metabolic
      conversion of 1-PP to 5-hydroxy-1-(2-pyrimidinyl)-piperazine (HO-1-PP) in human
      liver microsomes (HLMs). The product HO-1-PP was quantified by a validated liquid
      chromatography-tandem mass spectrometry method. In the presence of NADPH, 1-PP
      (100 microM) was incubated separately with human cDNA-expressed cytochrome P450
      isozymes (including CYP2D6, 3A4, 1A2, 2A6, 2C9, 2C19, 2E1, and 2B6) at 37 degrees
      C. CYP2D6 catalyzed the formation of HO-1-PP from 1-PP. This catalytic activity
      was >95% inhibited by quinidine, a CYP2D6 inhibitor. HO-1-PP formation rates
      correlated well with the bufuralol 1-hydroxylase (CYP2D6) activities of
      individual HLMs. The formation of HO-1-PP followed a Michaelis-Menten kinetics
      with a K(m) of 171 microM and V(max) of 313 pmol/min x mg protein in HLMs.
      Collectively, these results indicate that polymorphic CYP2D6 is responsible for
      the conversion of 1-PP to HO-1-PP.

PMID- 15507543
TI  - The calcium-sensing receptor: a key factor in the pathogenesis of secondary
      hyperparathyroidism.
AB  - Serum calcium levels are regulated by the action of parathyroid hormone (PTH).
      Major drivers of PTH hypersecretion and parathyroid cell proliferation are the
      hypocalcemia and hyperphosphatemia that develop in chronic kidney disease
      patients with secondary hyperparathyroidism (SHPT) as a result of low calcitriol
      levels and decreased kidney function. Increased PTH production in response to
      systemic hypocalcemia is mediated by the calcium-sensing receptor (CaR).
      Furthermore, as SHPT progresses, reduced expression of CaRs and vitamin D
      receptors (VDRs) in hyperplastic parathyroid glands may limit the ability of
      calcium and calcitriol to regulate PTH secretion. Current treatment for SHPT
      includes the administration of vitamin D sterols and phosphate binders. Treatment
      with vitamin D is initially effective, but efficacy often wanes with further
      disease progression. The actions of vitamin D sterols are undermined by reduced
      expression of VDRs in the parathyroid gland. Furthermore, the calcemic and
      phosphatemic actions of vitamin D mean that it has the potential to exacerbate
      abnormal mineral metabolism, resulting in the formation of vascular
      calcifications. Effective new treatments for SHPT that have a positive impact on
      mineral metabolism are clearly needed. Recent research shows that drugs that
      selectively target the CaR, calcimimetics, have the potential to meet these
      requirements.

PMID- 15507544
TI  - Expression profile of a human inducible nitric oxide synthase promoter reporter
      in transgenic mice during endotoxemia.
AB  - Inducible nitric oxide synthase (iNOS) is involved in many physiological and
      pathophysiological processes, including septic shock and acute kidney failure.
      Little is known about transcriptional regulation of the human iNOS gene in vivo
      under basal conditions or in sepsis. Accordingly, we developed transgenic mice
      carrying an insertional human iNOS promoter-reporter gene construct. In these
      mice, the proximal 8.3 kb of the human iNOS 5'-flanking region controls
      expression of the reporter gene of enhanced green fluorescent protein (EGFP).
      Patterns of human iNOS promoter/EGFP transgene expression in tissues were
      examined by fluorescence microscopy and immunoblotting. Endogenous murine iNOS
      was basally undetectable in kidney, intestine, spleen, heart, lung, liver,
      stomach, or brain. In contrast, EGFP from the transgene was basally expressed in
      kidney, brain, and spleen, but not the other tissues of the transgenic mice.
      Bacterial lipopolysaccharide induced endogenous iNOS expression in kidney,
      intestine, spleen, lung, liver, stomach, and heart, but not brain. In contrast,
      human iNOS promoter/EGFP transgene expression was induced above basal levels only
      in intestine, spleen, brain, stomach, and lung. Within kidney, human iNOS
      promoter/EGFP fluorescence was detected most prominently in proximal tubules of
      the outer cortex and collecting ducts and colocalized with endogenous mouse iNOS.
      Within the collecting duct, both endogenous iNOS and the human iNOS promoter/EGFP
      transgene were expressed in cells lacking aquaporin-2 immunoreactivity,
      consistent with expression in intercalated cells. Although it remains possible
      that essential regulatory elements reside in remote locations of the gene, our
      data concerning this 8.3-kb region provide the first in vivo evidence suggesting
      differential transcriptional control of the human iNOS gene in these organs and
      marked differences in transcriptional regulatory regions between the murine and
      human genes.

PMID- 15507545
TI  - Renal medullary gene expression in aquaporin-1 null mice.
AB  - Mice that lack the aquaporin-1 gene (AQP1) lack a functional countercurrent
      multiplier mechanism, fail to concentrate the inner medullary (IM) interstitium,
      and present with a urinary concentrating defect. In this study, we use DNA
      microarrays to identify the gene expression profile of the IM of AQP1 null mice
      and corresponding changes in gene expression resulting from a loss of a
      hypertonic medullary interstitium. An ANOVA analysis model, CARMA, was used to
      isolate the knockout effect while taking into account experimental variability
      associated with microarray studies. In this study 5,701 genes of the possible
      approximately 12,000 genes on the array were included in the ANOVA; 531 genes
      were identified as demonstrating a >1.5-fold up- or downregulation between the
      wild-type and knockout groups. We randomly selected 35 genes for confirmation by
      real-time PCR, and 29 of the 35 genes were confirmed using this method. The
      overall pattern of gene expression in the AQP1 null mice was one of
      downregulation compared with gene expression in the renal medullas of the wild
      type mice. Heat shock proteins 105 and 94, aldose reductase, adenylate kinase 2,
      aldolase B, aldehyde reductase 6, and p8 were decreased in the AQP1 null mice.
      Carboxylesterase 3, matrilin 2, lipocalin 2, and transforming growth factor-alpha
      were increased in IM of AQP1 null mice. In addition, we observed a loss of
      vasopressin type 2 receptor mRNA expression in renal medullas of the AQP1 null
      mice. Thus the loss of the hyperosmotic renal interstitium, due to a loss of the
      concentrating mechanism, drastically altered not only the phenotype of these
      animals but also their renal medullary gene expression profile.

PMID- 15507546
TI  - TNF-alpha mediates obstruction-induced renal tubular cell apoptosis and
      proapoptotic signaling.
AB  - Obstruction of the upper urinary tract induces a progressive loss in renal mass
      through apoptotic renal cell death. Although TNF-alpha has been implicated in
      ischemia-reperfusion-induced apoptotic renal cell death, its role in obstructive
      renal cell apoptosis remains unknown. To study this, male Sprague-Dawley rats
      were subjected to left unilateral ureteral obstruction vs. sham operation. Twenty
      four hours before surgery and every 84 h thereafter, rats received either vehicle
      or a pegylated form of soluble TNF receptor type 1 (PEG-sTNFR1). The kidneys were
      harvested 1, 3, or 7 days postoperatively, and tissue samples were subsequently
      analyzed for TNF-alpha (ELISA, RT-PCR), Fas ligand (RT-PCR), apoptosis (TUNEL,
      ELISA), and caspase 8 and 3 activity (Western blot). Renal obstruction induced
      increased tissue TNF-alpha and Fas ligand mRNA levels, TNF-alpha protein
      production, apoptotic renal tubular cell death, and elevated caspase 8 and 3
      activity, whereas treatment with PEG-sTNFR1 significantly reduced obstruction
      induced TNF-alpha production, renal tubular cell apoptosis, and caspase activity.
      PEG-sTNFR1 did not significantly alter Fas ligand expression. These results
      demonstrate that TNF-alpha mediates obstruction-induced renal tubular cell
      apoptosis and proapoptotic signaling and identify TNF-alpha neutralization as a
      potential therapeutic option for the amelioration of obstruction-induced renal
      injury.

PMID- 15507547
TI  - HMG-CoA reductase inhibition reverses LCAT and LDL receptor deficiencies and
      improves HDL in rats with chronic renal failure.
AB  - Dyslipidemia is a prominent feature of chronic renal failure (CRF) and a major
      risk factor for atherosclerosis and the progression of renal disease. CRF-induced
      dyslipidemia is marked by hypertriglyceridemia and a shift in plasma cholesterol
      from HDL to the ApoB-containing lipoproteins. Several studies have demonstrated a
      favorable response to administration of 3-hydroxy-3-methylglutaryl (HMG)-CoA
      reductase inhibitors (statins) in CRF. This study was intended to explore the
      effect of statin therapy on key enzymes and receptors involved in cholesterol
      metabolism. Accordingly, CRF (5/6 nephrectomized) and sham-operated rats were
      randomized to untreated and statin-treated (rosuvastatin 20 mg x kg(-1) x day(
      1)) groups and observed for 6 wk. The untreated CRF rats exhibited increased
      total cholesterol-to-HDL cholesterol ratio, diminished plasma
      lecithin:cholesterol acyltransferase (LCAT) and the hepatic LDL receptor,
      elevated hepatic acyl-CoA:cholesterol acyltransferase (ACAT), and no change in
      hepatic HMG-CoA reductase, cholesterol 7alpha-hydroxylase, or HDL receptor (SRB
      1). Statin administration lowered HMG-CoA reductase activity, normalized plasma
      LCAT, total cholesterol-to-HDL cholesterol ratio, and hepatic LDL receptor but
      did not significantly change either plasma total cholesterol, hepatic cholesterol
      7alpha-hydroxylase, total ACAT activity, or SRB-1 in the CRF animals. Statin
      administration to the normal control rats led to significant increases in plasma
      LCAT and hepatic LDL receptor, significant reductions of total cholesterol-to-HDL
      cholesterol ratio, hepatic HMG-CoA reductase activity, and cholesterol 7alpha
      hydroxylase abundance with virtually no change in plasma cholesterol
      concentration. Thus administration of rosuvastatin reversed LCAT and LDL receptor
      deficiencies and promoted a shift in plasma cholesterol from ApoB-containing
      lipoproteins to HDL in CRF rats.

PMID- 15507548
TI  - Competency-based training: where will it lead us?

PMID- 15507549
TI  - Legalism, postmodernism, and the vicissitudes of teaching ethics.

PMID- 15507550
TI  - The dilemma of hidden ethical dilemmas.

PMID- 15507551
TI  - The positive role of professionalism and ethics training in medical education: a
      comparison of medical student and resident perspectives.
AB  - OBJECTIVE: To assess the perspectives and preferences of medical students and
      residents regarding professionalism and ethics education. METHODS: A new written
      survey with 124 items (scale: "strongly disagree" = 1, "strongly agree" = 9) was
      sent to all medical students (n=308) and PGY 1-3 residents (n=233) at one
      academic center. RESULTS: Of the 336 participants (200 students, 65% response;
      136 residents 58% response), only 18% found current professionalism and ethics
      preparation sufficient. Respondents endorsed professionalism (means=7.48 to 8.11)
      and ethics topics (means=6.56 to 6.87), women more so than men (p<0.05).
      Respondents preferred clinically- and expert-oriented learning over formal,
      nontraditional, or independent approaches (p<0.0001). They preferred clinically
      oriented assessment methods (p<0.0001), residents more so than medical students
      (p<0.0001). On several items, psychiatry residents expressed greater
      receptiveness to professionalism and ethics preparation. CONCLUSIONS: Medical
      students and residents indicate support for professionalism and ethics
      educational initiatives, including diverse curricular topics and clinically
      attuned assessments.

PMID- 15507552
TI  - Hidden ethical dilemmas in psychiatric residency training: the psychiatry
      resident as dual agent.
AB  - In addition to learning about confidentiality, civil commitment, informed
      consent, and other ethical issues, psychiatry residents must deal with less
      visible ethical dilemmas that arise from the training process itself. Residents
      grapple with three inherent conflicting duties between their dual roles as
      physician and learner, as physician and supervisee, and as physician and employee
      of a training institution. These conflicts must be negotiated at a time of high
      stress, when residents are plagued with self-doubt, fear, fatigue, and other
      vulnerabilities that can lead good doctors to make ethically dubious decisions.
      While such conflicts and stressors are common to residency training in most
      specialties, they may be heightened in psychiatric residency. This paper proposes
      a model for understanding covert elements of ethical decision making during
      psychiatric residency and recommends strategies training programs can use to help
      residents navigate an ethical minefield.

PMID- 15507553
TI  - Can one portfolio measure the six ACGME general competencies?
AB  - OBJECTIVE: To determine that portfolios, useable by any program, can provide
      needed evidence of resident performance within the ACGME general competencies.
      METHODS: Eighteen residents constructed portfolios with selected entries from
      thirteen psychiatric skills. Two raters assessed whether entries reflected
      resident performance within the general competencies. They indicated no (0), some
      (1), or definite evidence (2) for each competency. Median scores were reported by
      competency and psychiatric skill. RESULTS: Eighty entries were rated: 100% of the
      psychiatric skills reflected some evidence for medical knowledge; 92% provided
      some evidence for patient care, communication and interpersonal skills, and
      professionalism; 77% provided some evidence for systems-based practice, and 31%
      provided some evidence for practice-based learning. Ten of the 13 skills
      reflected evidence for at least five of the competencies. CONCLUSIONS: Any
      combination of five entries reflects all competencies with the exception of
      practice-based learning. This deficit can be corrected with revision of portfolio
      guidelines.

PMID- 15507554
TI  - Use of a computerized evaluation system in a psychiatry clerkship.
AB  - OBJECTIVE: Paper-based evaluations of medical students on clerkships are
      inefficient and time consuming to compile and analyze. To improve the evaluation
      process, the authors developed a web-based program. METHODS: A secure web-based
      system was designed to collect evaluations of students and their feedback about
      the clerkship. Acceptance, compliance, and impact of the web-based system on the
      clerkship were assessed. RESULTS: The web-based program was universally accepted
      by medical students who have been 100% compliant with prompt completion of their
      evaluations of the rotation. Most of the preceptors have utilized the program,
      resulting in a more timely receipt of their evaluations of students. The web
      based program computes numerical scores, compiles comments, and formats reports.
      The clerkship director has unlimited access to all of the data, which allows for
      efficient and timely communication with preceptors, medical students, and the
      dean's office. CONCLUSIONS: During the clerkship, the web-based program for
      evaluation and feedback has improved the efficiency of the evaluation process and
      the timely communication with students and preceptors.

PMID- 15507555
TI  - Addiction training scale: pilot study of a self-report evaluation tool for
      psychiatry residents.
AB  - OBJECTIVE: Alcohol and drug dependence disorders have become common public health
      hazards. Psychiatrists encounter these problems in a major portion of their
      patients. However, recent data suggest that their training does not provide them
      the confidence to treat these disorders. Current methods of evaluating residents
      fail to adequately ascertain the lack of confidence in substance abuse training.
      Here, we present the Addiction Training Scale (ATS) that we developed to help
      trainers identify deficits in residents' substance abuse training. METHOD: We
      developed the ATS and conducted a pilot study with the psychiatry residents at
      the Creighton University Department of Psychiatry, to test the validity of the
      ATS as a self-report evaluation tool to measure the level of psychiatry
      residents' preparedness in treating substance abuse disorders. RESULTS: Our
      results suggest that the ATS is related to the confidence and preparedness that
      residents express in their ability to treat substance abuse problems. CONCLUSION:
      The ATS may be beneficial in assessing psychiatry residents' substance abuse
      training and identifying deficits, which may be addressed during training.

PMID- 15507556
TI  - Creation of a web-based lecture series for psychiatry clerkship students: initial
      findings.
AB  - OBJECTIVE: In recent years, the trend in medical education has been to utilize
      clerkship settings outside the medical school. Subsequently, students rotate at
      distant sites from the main campus and have lectures of varying quantity and
      quality. The objective of the present study was to standardize the core didactic
      experience for students in the Psychiatry clerkship by using web-based lectures
      and to assess student satisfaction with such lectures. METHODS: Students
      completed a brief satisfaction questionnaire after viewing both web-based and
      live lectures. RESULTS: Students rated both web-based and live lectures
      positively, although overall satisfaction ratings were higher for live lectures.
      Shelf-exam scores improved for the current year, suggesting that learning was not
      negatively affected by the use of web-based lectures. CONCLUSIONS: Web-based
      lectures appear to be a feasible and satisfactory way to ensure didactic
      comparability across clinical sites.

PMID- 15507557
TI  - The adult learner rediscovered: psychiatry residents' push for cognitive
      behavioral therapy training and a learner-driven model of educational change.
AB  - OBJECTIVE: This study surveyed residents' experiences learning an emerging area
      of demand in psychiatry at a time when there is a lag in training resources.
      Unexpectedly, the data generated useful evidence in support of adult learning
      theory. The result is a post hoc examination of learner attitudes and activities
      during the spread of a new medical content domain. Implications of the results
      for adult learning theory are considered. METHODS: A survey evaluating interest,
      motivation, perceptions, and barriers toward learning cognitive-behavioral
      therapy (CBT) was given to 85 psychiatry residents at a single institution, with
      a 95% return rate and even distribution across years of training. RESULTS: The
      vast majority of residents were highly interested and motivated to learn CBT. One
      hundred percent considered CBT clinically useful, and 99% anticipated using it in
      future practice. Consistent with the model of adult learning theory, reasons for
      seeking CBT training tended to focus on personal interest (86%), motivation
      (81%), and opinion of its clinical usefulness (68%). Only a minority considered
      training requirements a motivation for seeking training (44%). The most commonly
      reported difficulty in gaining exposure to CBT was supervisor availability (65%).
      CONCLUSIONS: Residents exhibited qualities of adult learners for whom personal
      interests were more important than training requirements with regard to seeking
      training in new modes of treatment. In the wake of recent theoretical scrutiny of
      adult learning and its applicability to undergraduate medicine, these results
      suggest that postgraduate medicine might be uniquely suited to the study of adult
      learning theory.

PMID- 15507558
TI  - Teaching residents and program directors about physician impairment.
AB  - OBJECTIVE: Residents are at a higher risk than the general population for the
      development of stress-related problems, depression, or suicide. The authors
      describe a curriculum for educating PGY-1s and residency program directors about
      physician impairment. METHODS: A resident wellness program was established with
      the goals of preventing resident suicide, encouraging acceptance of treatment
      where appropriate, preventing self-prescribing, and aiding in stress management.
      RESULTS: The curriculum was rated highly by residents in the areas of program
      content and usefulness. CONCLUSIONS: Residents are receptive to education on
      physician impairment. Institutional support is necessary for effectively
      addressing these concerns with trainees.

PMID- 15507559
TI  - A psychiatric residency curriculum on the care of African American patients.
AB  - Training psychiatric residents to address cross-cultural issues in their practice
      of psychiatry is a necessary objective of contemporary psychiatric education.
      Cultural issues play a critical role in the formation and expression of a
      patient's personality. In addition, they are a major determinant of the context
      in which mental illness develops. This proposed curriculum outlines a systematic
      progression toward cultural competence with populations of African descent. It
      begins with increasing the residents' awareness of their own cultural identity.
      The concept of achieving cultural competence as a continuum is utilized. Trainees
      should be prepared for any unfavorable reactions to this novel material. The
      curriculum must include accurate historic information about black culture, and
      general topics of diagnosis and treatment of African Americans must be covered.
      This should occur in congruence with trainees' development from students to
      residents to psychiatrists, as they move from inpatient to outpatient, hospital
      to community, close supervision to autonomous functioning, gaining both skill and
      confidence.

PMID- 15507560
TI  - Burnout comparison among residents in different medical specialties.
AB  - OBJECTIVE: To investigate resident burnout in relation to work and home-related
      factors. METHOD: Maslach Burnout Inventory was mailed to residents in eight
      different medical specialties, with a response rate of 35%. RESULTS: Overall, 50%
      of residents met burnout criteria, ranging from 75% (obstetrics/gynecology) to
      27% (family medicine). The first year of residency, being single, personal
      stress, and dissatisfaction with faculty were independently associated with
      burnout. CONCLUSIONS: Efforts to reduce resident burnout nationally would benefit
      from expanding beyond the work-hours regulation.

PMID- 15507561
TI  - Teaching psychiatric residents about women and leadership.
AB  - OBJECTIVE: The purpose of this project was to develop a seminar on women as
      leaders within an academic department of psychiatry and to evaluate its
      effectiveness. METHODS: A seminar was offered as an elective to all residents
      within the Yale University Department of Psychiatry. Didactic presentations and
      open discussion were structured around the following topics: 1) exploration of
      leadership roles in various areas, including research, clinical practice,
      teaching, and administration; 2) organizational dynamics and gender; 3)
      negotiation skills and conflict resolution strategies; 4) role of consultation,
      seminars, peer support and mentoring by both men and women in the development of
      leadership skills; and 5) "keeping the balance: work, relationships, and personal
      health." The 13 participants were queried at the completion of the seminar, and a
      follow-up survey was performed 18 months later. RESULTS: The initial and follow
      up evaluations were quite positive, with average ratings in the "excellent" range
      at both points. The 10 respondents at 18 months were unanimous that there had
      been a positive and lasting effect on their professional lives. CONCLUSION: A
      seminar on women as leaders was a successful venture within an academic
      department of psychiatry. The structure of the course, which incorporated
      specific teaching materials plus "local" expertise, could serve as a model for
      such seminars in other programs or could be integrated into an existing course
      for all residents.

PMID- 15507562
TI  - Helping medical students understand postpartum psychosis through the prism of
      "The Yellow Wallpaper" by Charlotte Perkins Gilman.
AB  - OBJECTIVE: We assessed the use of literature to illustrate a postpartum
      depression lecture. METHODS: Medical students and faculty facilitators were
      surveyed after small group discussions. RESULTS: Students' ratings and comments
      were positive, and faculty comments were neutral to positive. CONCLUSION:
      Students valued this teaching method, while faculty observations reflected
      challenges of assessing literature's contributions to medical education in
      improving empathy and treatment outcome.

PMID- 15507563
TI  - Assessing psychotherapy competence.

PMID- 15507564
TI  - The need to define and study resident duty hours.

PMID- 15507565
TI  - A piece of my mind. Gomer.

PMID- 15507566
TI  - Jeremiah Stamler, MD: researcher, leader in cardiovascular disease prevention.

PMID- 15507576
TI  - Tenofovir, equivalence, and noninferiority.

PMID- 15507577
TI  - Enoxaparin vs unfractionated heparin in acute coronary syndrome.

PMID- 15507578
TI  - Enoxaparin vs unfractionated heparin in acute coronary syndrome.

PMID- 15507579
TI  - Emphysematous cystitis and renal stones in cystic fibrosis.

PMID- 15507580
TI  - Risk of community-acquired pneumonia and use of gastric acid-suppressive drugs.
AB  - CONTEXT: Reduction of gastric acid secretion by acid-suppressive therapy allows
      pathogen colonization from the upper gastrointestinal tract. The bacteria and
      viruses in the contaminated stomach have been identified as species from the oral
      cavity. OBJECTIVE: To examine the association between the use of acid-suppressive
      drugs and occurrence of community-acquired pneumonia. DESIGN, SETTING, AND
      PARTICIPANTS: Incident acid-suppressive drug users with at least 1 year of valid
      database history were identified from the Integrated Primary Care Information
      database between January 1, 1995, and December 31, 2002. Incidence rates for
      pneumonia were calculated for unexposed and exposed individuals. To reduce
      confounding by indication, a case-control analysis was conducted nested in a
      cohort of incident users of acid-suppressive drugs. Cases were all individuals
      with incident pneumonia during or after stopping use of acid-suppressive drugs.
      Up to 10 controls were matched to each case for practice, year of birth, sex, and
      index date. Conditional logistic regression was used to compare the risk of
      community-acquired pneumonia between use of proton pump inhibitors (PPIs) and H2
      receptor antagonists. MAIN OUTCOME MEASURE: Community-acquired pneumonia defined
      as certain (proven by radiography or sputum culture) or probable (clinical
      symptoms consistent with pneumonia). RESULTS: The study population comprised
      364,683 individuals who developed 5551 first occurrences of pneumonia during
      follow-up. The incidence rates of pneumonia in non-acid-suppressive drug users
      and acid-suppressive drug users were 0.6 and 2.45 per 100 person-years,
      respectively. The adjusted relative risk for pneumonia among persons currently
      using PPIs compared with those who stopped using PPIs was 1.89 (95% confidence
      interval, 1.36-2.62). Current users of H2-receptor antagonists had a 1.63-fold
      increased risk of pneumonia (95% confidence interval, 1.07-2.48) compared with
      those who stopped use. For current PPI users, a significant positive dose
      response relationship was observed. For H2-receptor antagonist users, the
      variation in dose was restricted. CONCLUSION: Current use of gastric acid
      suppressive therapy was associated with an increased risk of community-acquired
      pneumonia.

PMID- 15507581
TI  - Outcomes of percutaneous coronary interventions performed at centers without and
      with onsite coronary artery bypass graft surgery.
AB  - CONTEXT: An ongoing debate focuses on whether institutions should perform
      percutaneous coronary interventions (PCIs) without an onsite coronary artery
      bypass graft (CABG) surgery program. OBJECTIVE: To compare patient outcomes
      following PCI at US institutions performing this procedure without and with
      onsite cardiac surgery. DESIGN, SETTING, AND PATIENTS: Medicare hospital (part A)
      data were used to identify PCIs performed on fee-for-service Medicare enrollees
      (n = 625,854) aged at least 65 years at acute care facilities between January 1,
      1999, and December 1, 2001. Hospitals without and with onsite cardiac surgery
      were identified based on the presence of claims for CABG surgery. Patients were
      characterized as undergoing primary/rescue PCI, defined as an emergency procedure
      performed on the same day of admission for an acute myocardial infarction (MI),
      vs all other PCIs. MAIN OUTCOME MEASURES: Post-PCI CABG surgery and combined in
      hospital and 30-day mortality. RESULTS: A total of 178 hospitals performed PCIs
      without onsite cardiac surgery and 943 hospitals performed PCIs with onsite
      cardiac surgery. Patients undergoing PCIs in hospitals without onsite cardiac
      surgery were similar to those with onsite cardiac surgery with respect to age,
      sex, race, and measurable comorbidities; however, patients undergoing PCIs in
      hospitals without onsite cardiac surgery were more likely to have a
      primary/rescue PCI (22.0% vs 5.6%, P < .001). Patients undergoing PCIs in
      hospitals without cardiac surgery were more likely to die (6.0% vs 3.3%; adjusted
      odds ratio [OR], 1.29; 95% confidence interval [CI], 1.14-1.47; P < .001). After
      accounting for baseline differences, mortality for patients with primary/rescue
      PCI was similar in institutions without and with cardiac surgery (adjusted OR,
      0.93; 95% CI, 0.80-1.08; P = .34). However, for the larger non-primary/rescue PCI
      population, mortality was higher in hospitals without onsite cardiac surgery
      (adjusted OR, 1.38; 95% CI, 1.14-1.67; P=.001). This increase in mortality was
      primarily confined to hospitals performing 50 or less Medicare PCIs per year.
      CONCLUSIONS: Percutaneous coronary interventions in hospitals without onsite
      cardiac surgery are often performed for reasons other than immediate treatment of
      an MI and are associated with a higher risk of adverse outcomes. Policies aimed
      at increasing access to primary/rescue PCI through promoting PCI in hospitals
      without cardiac surgery may inadvertently lead to an overall increase in
      mortality related to PCI.

PMID- 15507582
TI  - Cognitive-behavior therapy, sertraline, and their combination for children and
      adolescents with obsessive-compulsive disorder: the Pediatric OCD Treatment Study
      (POTS) randomized controlled trial.
AB  - CONTEXT: The empirical literature on treatment of obsessive-compulsive disorder
      (OCD) in children and adolescents supports the efficacy of short-term OCD
      specific cognitive-behavior therapy (CBT) or medical management with selective
      serotonin reuptake inhibitors. However, little is known about their relative and
      combined efficacy. OBJECTIVE: To evaluate the efficacy of CBT alone and medical
      management with the selective serotonin reuptake inhibitor sertraline alone, or
      CBT and sertraline combined, as initial treatment for children and adolescents
      with OCD. DESIGN, SETTING, AND PARTICIPANTS: The Pediatric OCD Treatment Study, a
      balanced, masked randomized controlled trial conducted in 3 academic centers in
      the United States and enrolling a volunteer outpatient sample of 112 patients
      aged 7 through 17 years with a primary Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition diagnosis of OCD and a Children's Yale-Brown
      Obsessive-Compulsive Scale (CY-BOCS) score of 16 or higher. Patients were
      recruited between September 1997 and December 2002. INTERVENTIONS: Participants
      were randomly assigned to receive CBT alone, sertraline alone, combined CBT and
      sertraline, or pill placebo for 12 weeks. MAIN OUTCOME MEASURES: Change in CY
      BOCS score over 12 weeks as rated by an independent evaluator masked to treatment
      status; rate of clinical remission defined as a CY-BOCS score less than or equal
      to 10. RESULTS: Ninety-seven of 112 patients (87%) completed the full 12 weeks of
      treatment. Intent-to-treat random regression analyses indicated a statistically
      significant advantage for CBT alone (P = .003), sertraline alone (P = .007), and
      combined treatment (P = .001) compared with placebo. Combined treatment also
      proved superior to CBT alone (P = .008) and to sertraline alone (P = .006), which
      did not differ from each other. Site differences emerged for CBT and sertraline
      but not for combined treatment, suggesting that combined treatment is less
      susceptible to setting-specific variations. The rate of clinical remission for
      combined treatment was 53.6% (95% confidence interval [CI], 36%-70%); for CBT
      alone, 39.3% (95% CI, 24%-58%); for sertraline alone, 21.4% (95% CI, 10%-40%);
      and for placebo, 3.6% (95% CI, 0%-19%). The remission rate for combined treatment
      did not differ from that for CBT alone (P = .42) but did differ from sertraline
      alone (P = .03) and from placebo (P<.001). CBT alone did not differ from
      sertraline alone (P = .24) but did differ from placebo (P = .002), whereas
      sertraline alone did not (P = .10). The 3 active treatments proved acceptable and
      well tolerated, with no evidence of treatment-emergent harm to self or to others.
      CONCLUSION: Children and adolescents with OCD should begin treatment with the
      combination of CBT plus a selective serotonin reuptake inhibitor or CBT alone.

PMID- 15507583
TI  - Hospital- and patient-level characteristics and the risk of appendiceal rupture
      and negative appendectomy in children.
AB  - CONTEXT: The rates of appendiceal rupture and negative appendectomy in children
      remain high despite efforts to reduce them. Both outcomes are used as measures of
      hospital quality. Little is known about the factors that influence these rates.
      OBJECTIVE: To investigate the association between hospital- and patient-level
      characteristics and the rates of appendiceal rupture and negative appendectomy in
      children. DESIGN, SETTING, AND PATIENTS: Retrospective review using the Pediatric
      Health Information System database containing information on 24,411
      appendectomies performed on children aged 5 to 17 years at 36 pediatric hospitals
      in the United States between 1997 and 2002. MAIN OUTCOME MEASURES: Rates of
      negative appendectomy and appendiceal rupture; the odds ratio (OR) of negative
      appendectomy and appendiceal rupture by hospital, patient age, race, and health
      insurance status, and hospital fiscal year and appendectomy volume. Negative
      appendectomy rate was defined as the number of patients with appendectomy but
      without appendicitis divided by the total number of appendectomies. RESULTS: The
      median negative appendectomy rate was 3.06% (range, 1%-12%) and the median
      appendiceal rupture rate was 35.08% (range, 22%-62%). The adjusted OR for
      appendiceal rupture was higher in Asian children (1.66; 95% confidence interval
      [CI], 1.24-2.23) and black children (1.13; 95% CI, 1.01-1.30) compared with white
      children. Children without health insurance and children with public insurance
      had increased odds of appendiceal rupture compared with children who had private
      health insurance (adjusted OR, 1.36; 95% CI, 1.22-1.53 for self-insured; adjusted
      OR, 1.48; 95% CI, 1.34-1.64 for public insurance). No correlation existed between
      negative appendectomy rate and race, health insurance status, or hospital
      appendiceal rupture rate. The negative appendectomy rate improved as the hospital
      appendectomy volume increased. CONCLUSION: The rate of appendiceal rupture in
      school-aged children was associated with race and health insurance status and not
      with negative appendectomy rate and therefore is more likely to be associated
      with prehospitalization factors such as access to care, quality of care, and
      patient or physician education.

PMID- 15507584
TI  - Promotion and prescribing of hormone therapy after report of harm by the Women's
      Health Initiative.
AB  - CONTEXT: Little is known about how the pharmaceutical industry responds to
      evidence of harm associated with its products, such as the publication in July
      2002 of the Women's Health Initiative Estrogen Plus Progestin Trial (WHI E+P)
      report demonstrating that standard-dose Prempro produced significant harm and
      lacked net benefits. OBJECTIVE: To examine pharmaceutical industry response to
      the WHI E+P results by analyzing promotional expenditures for hormone therapy
      before and after July 2002. DESIGN AND SETTING: Nationally representative and
      prospectively collected longitudinal data (January 2001 through December 2003) on
      prescribing and promotion of hormone therapies were obtained from IMS Health and
      Consumer Media Reports. MAIN OUTCOME MEASURES: Trends in quarterly prescriptions
      for hormone therapy and expenditures on 5 modes of drug promotion: samples,
      office-based detailing, hospital-based promotion, journal advertisements, and
      direct-to-consumer advertising. RESULTS: Prior to the WHI E+P report, prescribing
      rates and promotional spending for hormone therapy were stable. In the quarter
      before the WHI E+P report (April-June 2002), 22.4 million prescriptions for
      hormone therapy were dispensed and 71 million dollars was spent on promotion (in
      annual terms, 350 dollars per year per US physician). Within 9 months of the
      report's publication (quarter 1 of 2003), there was a 32% decrease in hormone
      therapy prescriptions, and a nadir had been reached for promotional spending (37%
      decrease compared with pre-WHI E+P levels). Spending decreased for all
      promotional activities and most hormone therapies. Overall, the greatest declines
      were for samples (36% decrease as of quarter 1 of 2003) and direct-to-consumer
      advertising (100% decrease). The greatest declines in promotion occurred for
      standard-dose Prempro (61% decrease as of quarter 1 of 2003), the agent
      implicated by the WHI E+P report. More recently, promotional efforts have
      increased, particularly for lower-dose Prempro, a resurgence associated with
      modestly increased prescriptions for this newer agent. CONCLUSIONS: Concordant
      with its widespread use, hormone therapy was among the most heavily promoted
      medications prior to the WHI E+P report. Following reporting of the evidence of
      harm from this trial, there was a substantial decline in promotional spending for
      hormone therapy, particularly for the agents most directly implicated in the
      trial. Interrelated with the impact of the trial results themselves and the
      ensuing media coverage, reduced promotion may have contributed to a substantial
      decline in hormone therapy prescriptions.

PMID- 15507585
TI  - Does this patient have an instability of the shoulder or a labrum lesion?
AB  - CONTEXT: History taking and clinical tests are commonly used to diagnose shoulder
      pain. Unclear is whether tests and history accurately diagnose instability or
      intra-articular pathology (IAP). OBJECTIVE: To analyze the accuracy of clinical
      tests and history taking for shoulder instability or IAP. DATA SOURCES: Relevant
      studies identified through PubMed, EMBASE, CINAHL, and bibliographies of known
      primary and review articles. STUDY SELECTION: Studies comparing the performance
      of history items or physical examination with a reference standard were included.
      Studies on fibromyalgia, fractures, or systemic disorders were excluded. Of 1449
      articles, 35 were eligible, and 17 were selected. DATA EXTRACTION: Data were
      extracted on study population, clinical tests, reference tests, and outcome. The
      studies' methodological quality (patient spectrum, verification, blinding, and
      replication) was assessed with the Quality Assessment of Diagnostic Accuracy
      Studies (QUADAS) checklist. DATA SYNTHESIS: Six tests showed positive likelihood
      ratios (LRs) and confidence intervals (CIs). Tests favoring the diagnosis for
      establishing instability included: relocation (LR, 6.5; 95% CI, 3.0-14.0) and
      anterior release (LR, 8.3; 95% CI, 3.6-19). Tests showing promise for
      establishing labral lesions included: the biceps load I and II (LR, 29; 95% CI,
      7.3-115.0 and LR, 26; 95% CI, 8.6-80.0), respectively, pain provocation of Mimori
      (LR, 7.2; 95% CI, 1.6-32.0), and internal rotation resistance strength (LR, 25;
      95% CI, 8.1-76.0). The apprehension, clunk, release, load and shift, and sulcus
      sign tests proved less useful. Results should be cautiously interpreted because
      studies were completed in select populations in orthopedic practice, mostly
      assessed by the test designers, and evaluated in single studies only. No accuracy
      studies were found for history taking or for clinical tests in primary care.
      CONCLUSIONS: Shoulder complaints are frequently recurrent. Instability might
      cause some of these complaints. Best evidence supports the value of the
      relocation and anterior release tests. Symptoms related to IAP (labral tears)
      remain unclear. Most promising for establishing labral tears are currently the
      biceps load I and II, pain provocation of Mimori, and the internal rotation
      resistance strength tests.

PMID- 15507586
TI  - 10 years beyond the Health Security Act failure: subsequent developments and
      persistent problems.
AB  - Ten years after the failure of President Clinton's Health Security Act (HSA), the
      United States continues to face multiple stresses in health care, including large
      numbers of uninsured individuals, increasing costs, questions about quality, and
      dissatisfaction with managed care. Using the framework of the HSA-particularly
      universal coverage, spending and managed competition, insurance for low-income
      persons, and patients' rights-the post-HSA evolution and current status of the US
      health care system is traced and lessons to guide future actions are outlined.
      Neither incremental legislation nor private sector changes in health care
      organization and financing during the past decade have ameliorated the problems
      addressed by the HSA, and new troubles have emerged. These problems affect every
      group in the country and continue to deteriorate health care, yet there has been
      no political support for large-scale reform. The core components of a vision for
      future action-universal coverage, quality improvement, cost containment, and
      subsidies for the economically vulnerable-are essential. There is a pressing need
      to construct a clear vision that would tie together incremental steps into a
      rational approach to comprehensive reform and to actually move toward the
      realization of that vision.

PMID- 15507587
TI  - Ensuring access to health care: the Kerry plan.

PMID- 15507588
TI  - Ensuring access to health care: the Bush plan.

PMID- 15507589
TI  - Acid suppression and pneumonia: a clinical indication for rational prescribing.

PMID- 15507590
TI  - Is onsite surgery backup necessary for percutaneous coronary interventions?

PMID- 15507591
TI  - JAMA patient page. Obsessive-compulsive disorder.

PMID- 15507593
TI  - Dynamic control of nuclear receptor transcription.
AB  - This Perspective highlights experiments that probe the complexity and regulation
      underlying cyclical association of nuclear receptor transcriptional complexes
      with DNA. Using advanced in vivo and in vitro techniques, these studies emphasize
      the importance of chromatin remodeling and histone modification in defining the
      timing and nature of the cycles. In addition, they reveal the multiplicity of
      receptor-coregulator complexes that reside on a single promoter. These conceptual
      and technical achievements integrate kinetic and combinatorial regulation into a
      new dynamic model of nuclear receptor-mediated transcription.

PMID- 15507594
TI  - UV laser cross-linking: a real-time assay to study dynamic protein/DNA
      interactions during chromatin remodeling.
AB  - We describe the use of laser ultraviolet (UV) cross-linking to study the
      interaction of transcription factors with in vitro assembled chromatinized DNA
      templates in real time. Because the laser source delivers a high density of
      photons in a single ns pulse, the cross-linking reaction is completed in less
      than 1 microseconds, allowing the investigator to freeze rapid dynamic changes in
      protein-DNA interactions. Using this approach, we have sampled the dynamic
      equilibrium of the glucocorticoid receptor (GR) and the chromatin remodeling
      complex (SWI/SNF) during adenosine triphosphate (ATP)-dependent chromatin
      remodeling on a chromatinized mouse mammary tumor virus promoter in vitro. UV
      laser cross-linking shows that the GR and SWI/SNF complex undergoes a periodic
      binding and displacement event during the process of chromatin remodeling. The
      assay provides unique information regarding the equilibrium of protein-DNA
      interactions in real time and can be easily adapted to study the dynamic events
      in the assembly and disassembly of other multiprotein complexes on chromatin or
      DNA templates.

PMID- 15507595
TI  - Selective gene expression in multigene families from yeast to mammals.
AB  - Exclusive gene expression, where only one member of a gene or gene cassette
      family is selected for expression, plays an important role in the establishment
      of cell identity in several biological systems. Here, we compare four such
      systems: mating-type switching in fission and budding yeast, where cells choose
      between expressing one of the two different mating-type cassettes, and
      immunoglobulin and odorant receptor gene expression in mammals, where the number
      of gene choices is substantially higher. The underlying mechanisms that establish
      this selective expression pattern in each system differ in almost every detail.
      In all four systems, once a successful gene activation event has taken place, a
      feedback mechanism affects the fate of the cell. In the mammalian systems,
      feedback is mediated by the expressed cell surface receptor to ensure monoallelic
      gene expression, whereas in the yeasts, the expressed gene cassette at the mating
      type locus affects donor choice during the subsequent switching event.

PMID- 15507597
TI  - Upregulation of RANTES gene expression in neuroglia by Japanese encephalitis
      virus infection.
AB  - Infection with Japanese encephalitis virus (JEV) causes cerebral inflammation and
      stimulates inflammatory cytokine expression. Glial cells orchestrate immunocyte
      recruitment to focal sites of viral infection within the central nervous system
      (CNS) and synchronize immune cell functions through a regulated network of
      cytokines and chemokines. Since immune cell infiltration is prominent, we
      investigated the production of a responding chemoattractant, RANTES (regulated
      upon activation, normal T-cell expressed and secreted), in response to JEV
      infection of glial cells. Infection with JEV was found to elicit the production
      of RANTES from primary neurons/glia, mixed glia, microglia, and astrocytes but
      not from neuron cultures. The production of RANTES did not seem to be directly
      responsible for JEV-induced neuronal death but instead contributed to the
      recruitment of immune cells. RANTES expression required viral replication and the
      activation of extracellular signal-regulated kinase (ERK) as well as
      transcription factors, including nuclear factor kappa B (NF-kappaB) and nuclear
      factor IL-6 (NF-IL-6). The induction of RANTES expression by JEV infection in
      glial cells needed the coordinate activation of NF-kappaB and NF-IL-6. Using
      enzymatic inhibitors, we demonstrated a strong correlation between the ERK
      signaling pathway and RANTES expression. However, JEV replication was not
      dependent on the activation of ERK, NF-kappaB, and NF-IL-6. Altogether, these
      results demonstrated that infection of glial cells by JEV provided the early ERK
      , NF-kappaB-, and NF-IL-6-mediated signals that directly activated RANTES
      expression, which might be involved in the initiation and amplification of
      inflammatory responses in the CNS.

PMID- 15507596
TI  - Construction of a herpes simplex virus type 1 mutant with only a three-nucleotide
      change in the branchpoint region of the latency-associated transcript (LAT) and
      the stability of its two-kilobase LAT intron.
AB  - Previous studies using a eukaryotic expression system indicated that the unusual
      stability of the latency-associated transcript (LAT) intron was due to its
      nonconsensus branchpoint sequence (T.-T Wu, Y.-H. Su, T. M. Block, and J. M.
      Taylor, Virology, 243:140-149, 1998). The present study investigated the role of
      the branchpoint sequence in the stability of the intron expressed from the herpes
      simplex virus type 1 (HSV-1) genome and the role of LAT intron stability in the
      HSV-1 life cycle. A branchpoint mutant called Sy2 and the corresponding rescued
      viruses, SyRA and SyRB, were constructed. To preserve the coding sequence of the
      immediate early gene icp0, which overlaps with the branchpoint region of the 2-kb
      LAT, a 3-nucleotide mutation into the branchpoint region of the 2-kb LAT was
      introduced, resulting in a branchpoint that is 85% identical to the consensus
      intron branchpoint sequence of eukaryotic cells. As anticipated, there was a 90-
      to 96-fold reduction in 2-kb LAT accumulation following productive infection in
      tissue culture and latent infection in mice with Sy2, as determined by Northern
      blot analysis. These results clearly suggest that the accumulation of the 2-kb
      intron in tissue culture and in vivo is, at least in part, due to the
      nonconsensus branchpoint sequence of the LAT intron. Interestingly, a failure to
      accumulate LAT was associated with greater progeny production of Sy2 at a low
      multiplicity of infection (0.01) in tissue culture, but not in mice. However, the
      ability of mutant Sy2 to reactivate from trigeminal ganglia (TG) derived from
      latently infected mice was indistinguishable from that of wild-type virus, as
      assayed in the mouse TG explant reactivation system.

PMID- 15507598
TI  - The cauliflower mosaic virus 35S promoter extends into the transcribed region.
AB  - A 60-nucleotide region (S1) downstream of the transcription start site of the
      cauliflower mosaic virus 35S RNA can enhance gene expression. By using transient
      expression assays with plant protoplasts, this activity was shown to be at least
      partially due to the effect of transcriptional enhancers within this region. We
      identify sequence motifs with enhancer function, which are normally masked by the
      powerful upstream enhancers of the 35S promoter. A repeated CT-rich motif is
      involved both in enhancer function and in interaction with plant nuclear
      proteins. The S1 region can also enhance expression from heterologous promoters.

PMID- 15507599
TI  - Nonrandom dimerization of murine leukemia virus genomic RNAs.
AB  - Retroviral genomes consist of two unspliced RNAs linked noncovalently in a dimer.
      Although these two RNAs are generally identical, two different RNAs can be
      copackaged when virions are produced by coinfected cells. It has been assumed,
      but not tested, that copackaging results from random RNA associations in the
      cytoplasm to yield encapsidated RNA homodimers and heterodimers in Hardy-Weinberg
      proportions. Here, virion RNA homo- and heterodimerization were examined for
      Moloney murine leukemia virus (MLV) using nondenaturing Northern blotting and a
      novel RNA dimer capture assay. The results demonstrated that coexpressed MLV RNAs
      preferentially self-associated, even when RNAs were identical in known packaging
      and dimerization sequences or when they differed overall by less than 0.1%. In
      contrast, HIV-1 RNAs formed homo- and heterodimers in random proportions. We
      speculate that these species-specific differences in RNA dimer partner selection
      may at least partially explain the higher frequency of genetic recombination
      observed for human immunodeficiency virus type 1 than for MLV.

PMID- 15507600
TI  - Expression and localization of the Epstein-Barr virus-encoded protein kinase.
AB  - The protein kinase (PK) encoded by the Epstein-Barr Virus (EBV) BGLF4 gene is the
      only EBV protein kinase. The expression pattern of EBV PK during the reactivation
      of the viral lytic cycle and the subcellular localization of the protein were
      analyzed with a polyclonal antiserum raised against a peptide corresponding to
      the N terminus of EBV PK. Based on previously published data (E. Gershburg and J.
      S. Pagano, J. Virol. 76:998-1003, 2002) and the expression pattern described
      here, we conclude that EBV PK is an early protein that requires viral-DNA
      replication for maximum expression. By biochemical fractionation, the protein
      could be detected mainly in the nuclear fraction 4 h after viral reactivation in
      Akata cells. Nuclear localization could be visualized by indirect
      immunofluorescence in HeLa cells transiently expressing EBV BGLF4 in the absence
      of other viral products. Transient expression of 3'-terminal deletion mutants of
      EBV BGLF4 resulted in cytoplasmic localization, confirming the presence of a
      nuclear localization site in the C-terminal region of the protein. In contrast to
      the wild-type EBV PK, all of the mutants were unable to hyperphosphorylate EA-D
      during coexpression or to phosphorylate ganciclovir, as measured by an in-cell
      activity assay. Thus, the results demonstrate that the nuclear localization, as
      well as the kinase activity, of BGFL4 is dependent on an intact C-terminal
      region.

PMID- 15507601
TI  - New class of orthopoxvirus antiviral drugs that block viral maturation.
AB  - By using a homology-based bioinformatics approach, a structural model of the
      vaccinia virus (VV) I7L proteinase was developed. A unique chemical library of
      approximately 51,000 compounds was computationally queried to identify potential
      active site inhibitors. The resulting biased subset of compounds was assayed for
      both toxicity and the ability to inhibit the growth of VV in tissue culture
      cells. A family of chemotypically related compounds was found which exhibits
      selective activity against orthopoxviruses, inhibiting VV with 50% inhibitory
      concentrations of 3 to 12 microM. These compounds exhibited no significant
      cytotoxicity in the four cell lines tested and did not inhibit the growth of
      other organisms such as Saccharomyces cerevisiae, Pseudomonas aeruginosa,
      adenovirus, or encephalomyocarditis virus. Phenotypic analyses of virus-infected
      cells were conducted in the presence of active compounds to verify that the
      correct biochemical step (I7L-mediated core protein processing) was being
      inhibited. Electron microscopy of compound-treated VV-infected cells indicated a
      block in morphogenesis. Compound-resistant viruses were generated and resistance
      was mapped to the I7L open reading frame. Transient expression with the mutant
      I7L gene rescued the ability of wild-type virus to replicate in the presence of
      compound, indicating that this is the only gene necessary for resistance. This
      novel class of inhibitors has potential for development as an efficient antiviral
      drug against pathogenic orthopoxviruses, including smallpox.

PMID- 15507602
TI  - A retroviral promoter and a cellular enhancer define a bipartite element which
      controls env ERVWE1 placental expression.
AB  - The HERV-W family contains hundreds of loci diversely expressed in several
      physiological and pathological contexts. A unique locus termed ERVWE1 encodes an
      envelope glycoprotein (syncytin) involved in hominoid placental physiology. Here
      we show that syncytin expression is regulated by a bipartite element consisting
      of a cyclic AMP (cAMP)-inducible long terminal repeat (LTR) retroviral promoter
      adjacent to a cellular enhancer conferring a high level of expression and
      placental tropism. Deletion mutant analysis showed that the ERVWE1 5' LTR
      contains binding sites essential for basal placental activity in the region from
      positions +1 to +125. The region from positions +125 to +310 represents a cAMP
      responsive core HERV-W promoter active in all cell types. Site-directed
      mutagenesis analysis highlighted the complexity of U3 regulation. ERVWE1 placenta
      specific positive (e.g., T240) and negative (e.g., G71) regulatory sites were
      identified, as were essential sites required for basic activity (e.g., A247). The
      flanking sequences of the ERVWE1 provirus contain several putative regulatory
      elements. The upstream HERV-H and HERV-P LTRs were found to be inactive.
      Conversely, the 436-bp region located between the HERV-P LTR and ERVWE1 was shown
      to be an upstream regulatory element (URE) which is significantly active in
      placenta cells. This URE acts as a tissue-specific enhancer. Genetic and
      functional analyses of hominoid UREs revealed large differences between UREs of
      members of the Hominidae and the Hylobatidae. These data allowed the
      identification of a positive regulatory region from positions -436 to -128, a
      mammalian apparent LTR retrotransposon negative regulatory region from positions 
      128 to -67, and a trophoblast-specific enhancer (TSE) from positions -67 to -35.
      Putative AP-2, Sp-1, and GCMa binding sites are essential constituents of the 33
      bp TSE.

PMID- 15507603
TI  - Identification and characterization of persistent human erythrovirus infection in
      blood donor samples.
AB  - The presence of human erythrovirus DNA in 2,440 blood donations from the United
      Kingdom and sub-Saharan Africa (Ghana, Malawi, and South Africa) was screened.
      Sensitive qualitative and real-time quantitative PCR assays revealed a higher
      prevalence of persistent infection with the simultaneous presence of
      immunoglobulin G (IgG) and viral DNA (0.55 to 1.3%) than previously reported.
      This condition was characterized by a low viral load (median, 558 IU/ml; range,
      42 to 135,000 IU/ml), antibody-complexed virus, free specific IgG, and
      potentially infectious free virus. Human erythrovirus genotype 1 (formerly
      parvovirus B19) was prevalent in the United Kingdom, Malawi, and South Africa. In
      contrast, only human erythrovirus genotype 3 (erythrovirus variant V9) was
      prevalent in Ghana. Genotype 3 had considerable genetic diversity, clustering in
      two probable subtypes. Genotype 1-based antibody assays failed to detect 38.5% of
      Ghanaian samples containing antibodies to genotype 3 virus but did not fail to
      detect cases of persistent infection. This study indicates a potential African
      origin of genotype 3 human erythrovirus and considerable shortcomings in the
      tools currently used to diagnose erythrovirus infection.

PMID- 15507604
TI  - The l2 minor capsid protein of human papillomavirus type 16 interacts with a
      network of nuclear import receptors.
AB  - The L2 minor capsid proteins enter the nucleus twice during viral infection: in
      the initial phase after virion disassembly and in the productive phase when,
      together with the L1 major capsid proteins, they assemble the replicated viral
      DNA into virions. In this study we investigated the interactions between the L2
      protein of high-risk human papillomavirus type 16 (HPV16) and nuclear import
      receptors. We discovered that HPV16 L2 interacts directly with both Kapbeta(2)
      and Kapbeta(3). Moreover, binding of Ran-GTP to either Kapbeta(2) or Kapbeta(3)
      inhibits its interaction with L2, suggesting that the Kapbeta/L2 complex is
      import competent. In addition, we found that L2 forms a complex with the
      Kapalpha(2)beta(1) heterodimer via interaction with the Kapalpha(2) adapter. In
      agreement with the binding data, nuclear import of L2 in digitonin-permeabilized
      cells could be mediated by either Kapalpha(2)beta(1) heterodimers, Kapbeta(2), or
      Kapbeta(3). Mapping studies revealed that HPV16 L2 contains two nuclear
      localization signals (NLSs), in the N terminus (nNLS) and C terminus (cNLS), that
      could mediate its nuclear import. Together the data suggest that HPV16 L2
      interacts via its NLSs with a network of karyopherins and can enter the nucleus
      via several import pathways mediated by Kapalpha(2)beta(1) heterodimers,
      Kapbeta(2), and Kapbeta(3).

PMID- 15507605
TI  - Novel host range and cytopathic variant of ecotropic Friend murine leukemia
      virus.
AB  - A variant ecotropic Friend murine leukemia virus, F-S MLV, is capable of inducing
      the formation of large multinucleated syncytia in Mus dunni cells. This
      cytopathicity resembles that of Spl574 MLV, a novel variant recently isolated
      from the spleen of a Mus spicilegus mouse neonatally inoculated with Moloney MLV.
      F-S MLV is an N-tropic Friend MLV that also has the unusual ability to infect
      hamster cells, which are normally resistant to mouse ecotropic MLVs. Syncytium
      induction by both F-S MLV and Spl574 is accompanied by the accumulation of large
      amounts of unintegrated viral DNA, a hallmark of pathogenic retroviruses, but not
      previously reported for mouse ecotropic gammaretroviruses. Sequencing and site
      specific mutagenesis determined that the syncytium-inducing phenotype of F-S MLV
      can be attributed to a single amino acid substitution (S84A) in the VRA region of
      the viral env gene. This site corresponds to that of the single substitution
      previously shown to be responsible for the cytopathicity of Spl574, S82F. The
      S84A substitution in F-S MLV also contributes to the ability of this virus to
      infect hamster cells, but Spl574 MLV is unable to infect hamster cells. Because
      this serine residue is one of the critical amino acids that form the CAT-1
      receptor binding site, and because M. dunni and hamster cells have variant CAT-1
      receptors, these results suggest that syncytium formation as well as altered host
      range may be a consequence of altered interaction between virus and receptor.

PMID- 15507607
TI  - De novo initiation pocket mutations have multiple effects on hepatitis C virus
      RNA-dependent RNA polymerase activities.
AB  - The hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) has several
      distinct biochemical activities, including initiation of RNA synthesis by a de
      novo mechanism, extension from a primed template, nontemplated nucleotide
      addition, and synthesis of a recombinant RNA product from two or more
      noncovalently linked templates (template switch). All of these activities require
      specific interaction with nucleoside triphosphates (NTPs). Based on the structure
      of the HCV RdRp bound to NTP (S. Bressanelli, L. Tomei, F. A. Rey, and R.
      DeFrancesco, J. Virol. 76:3482-3492, 2002), we mutated the amino acid residues
      that contact the putative initiation GTP and examined the effects on the various
      activities. Although all mutations retained the ability for primer extension,
      alanine substitution at R48, R158, R386, R394, or D225 decreased de novo
      initiation, and two or more mutations abolished de novo initiation. While the
      prototype enzyme had a K(m) for GTP of 3.5 microM, all of the mutations except
      one had K(m)s that were three- to sevenfold higher. These results demonstrate
      that the affected residues are functionally required to interact with the
      initiation nucleotide. Unexpectedly, many of the mutations also affected the
      addition of nontemplated nucleotide, indicating that residues in the initiating
      NTP (NTPi)-binding pocket are required for nontemplated nucleotide additions.
      Interestingly, mutations in D225 are dramatically affected in template switch,
      indicating that this residue of the NTPi pocket also interacts with components in
      the elongation complex. We also examined the interaction of ribavirin
      triphosphate with the NTPi-binding site.

PMID- 15507606
TI  - Cell cycle arrest in G2 induces human immunodeficiency virus type 1
      transcriptional activation through histone acetylation and recruitment of CBP, NF
      kappaB, and c-Jun to the long terminal repeat promoter.
AB  - In human immunodeficiency virus type 1 (HIV-1)-infected cells, a cell cycle
      arrest in G(2) increases viral expression and may represent a strategy for the
      virus to optimize its expression. In latently infected cells, balance between
      viral silencing and reactivation relies on the nucleosomal organization of the
      integrated long terminal repeat (LTR). It is shown here that nucleosome nuc-1,
      which is located downstream of the TATA box, is specifically modified when
      latently infected cells are arrested in G(2) by chemical inducers. Notably,
      histones H3 and H4 are hyperacetylated, and this modification is associated with
      an increased LTR-driven transcription. nuc-1 hyperacetylation is also associated
      with the recruitment of histone acetyltransferase CBP and transcription factors
      NF-kappaB and c-Jun. NF-kappaB and/or c-Jun binding to the LTR in G(2)-arrested
      cells appears to be required for CBP recruitment as well as for nuc-1 remodeling
      and viral reactivation.

PMID- 15507608
TI  - The severe acute respiratory syndrome coronavirus Nsp15 protein is an
      endoribonuclease that prefers manganese as a cofactor.
AB  - Nonstructural protein 15 (Nsp15) of the severe acute respiratory syndrome
      coronavirus (SARS-CoV) produced in Escherichia coli has endoribonuclease activity
      that preferentially cleaved 5' of uridylates of RNAs. Blocking either the 5' or
      3' terminus did not affect cleavage. Double- and single-stranded RNAs were both
      substrates for Nsp15 but with different kinetics for cleavage. Mn(2+) at 2 to 10
      mM was needed for optimal endoribonuclease activity, but Mg(2+) and several other
      divalent metals were capable of supporting only a low level of activity.
      Concentrations of Mn(2+) needed for endoribonuclease activity induced significant
      conformation change(s) in the protein, as measured by changes in tryptophan
      fluorescence. A similar endoribonucleolytic activity was detected for the
      orthologous protein from another coronavirus, demonstrating that the
      endoribonuclease activity of Nsp15 may be common to coronaviruses. This work
      presents an initial biochemical characterization of a novel coronavirus
      endoribonuclease.

PMID- 15507610
TI  - Vesicular stomatitis virus evolution during alternation between persistent
      infection in insect cells and acute infection in mammalian cells is dominated by
      the persistence phase.
AB  - Vesicular stomatitis virus has the potential for very rapid evolution in the
      laboratory, but like many other arboviruses, it evolves at a relatively slow rate
      in the natural environment. Previous work showed that alternating replication in
      different cell types does not promote stasis. In order to determine whether other
      factors promote stasis, we compared the fitness trajectories of populations
      evolving during acute infections in mammalian cells, populations evolving during
      persistent infections in insect cells, and populations evolving during
      alternating acute and persistent infection cycles. Populations evolving under
      constant conditions increased in fitness in the environment in which they
      replicated. An asymmetric trade-off was observed such that acute infection had no
      cost for persistence but persistent replication had a dramatic cost for acute
      infection in mammalian cells. After an initial period of increase, fitness
      remained approximately constant in all the populations that included persistent
      replication, but fitness continuously increased in populations evolving during
      acute infections. Determination of the consensus sequence of the genes encoding
      the N, P, M, and G proteins showed that the pattern of mutation accumulation was
      coherent with fitness changes during persistence so that once fitness reached a
      maximum, the rate of mutation accumulation dropped. Persistent replication
      dominated both the genetic and the phenotypic evolution of the populations that
      alternated between acute infection of mammalian cells and persistence in insect
      cells, and fitness loss was observed in the mammalian environment despite
      periodic replication in mammalian cells. These results show that stasis can be
      achieved without good levels of adaptation to both the mammalian and the insect
      environments.

PMID- 15507609
TI  - Analysis of adaptive mutations in Kunjin virus replicon RNA reveals a novel role
      for the flavivirus nonstructural protein NS2A in inhibition of beta interferon
      promoter-driven transcription.
AB  - The establishment of persistent noncytopathic replication by replicon RNAs of a
      number of positive-strand RNA viruses usually leads to generation of adaptive
      mutations in nonstructural genes. Some of these adaptive mutations (e.g., in
      hepatitis C virus) increase the ability of RNA replication to resist the
      antiviral action of alpha/beta interferon (IFN-alpha/beta); others (e.g., in
      Sindbis virus) may also lead to more efficient IFN production. Using puromycin
      selectable Kunjin virus (KUN) replicon RNA, we identified two adaptive mutations
      in the NS2A gene (producing Ala30-to-Pro and Asn101-to-Asp mutations in the gene
      product; for simplicity, these will be referred to hereafter as Ala30-to-Pro and
      Asn101-to-Asp mutations) that, when introduced individually or together into the
      original wild-type (wt) replicon RNA, resulted in approximately 15- to 50-fold
      more efficient establishment of persistent replication in hamster (BHK21) and
      human (HEK293 and HEp-2) cell lines. Transfection with a reporter plasmid
      carrying the luciferase gene under the control of the IFN-beta promoter resulted
      in approximately 6- to 7-fold-higher luciferase expression in HEp-2 cells stably
      expressing KUN replicon RNA with an Ala30-to-Pro mutation in the NS2A gene
      compared to that observed in HEp-2 cells stably expressing KUN replicon RNA with
      the wt NS2A gene. Moreover, cotransfection of plasmids expressing individual wt
      or Ala30-to-Pro-mutated NS2A genes with the IFN-beta promoter reporter plasmid,
      followed by infection with Semliki Forest virus to activate IFN-beta promoter
      driven transcription, showed approximately 7-fold inhibition of luciferase
      expression by the wt but not by the Ala30-to-Pro-mutated NS2A protein. The
      results show for the first time a role for the flavivirus nonstructural protein
      NS2A in inhibition of IFN-beta promoter-driven transcription and identify a
      single-amino-acid mutation in NS2A that dramatically reduces this inhibitory
      activity. The findings determine a new function for NS2A in virus-host
      interactions, extend the range of KUN replicon vectors for noncytopathic gene
      expression, and identify NS2A as a new target for attenuation in the development
      of live flavivirus vaccines.

PMID- 15507612
TI  - Cellular immune responses in seronegative sexual contacts of acute hepatitis C
      patients.
AB  - Acute hepatitis C virus (HCV) is typically defined as new viremia and antibody
      seroconversion. Rates and immunologic correlates of hepatitis C clearance have
      therefore been based on clearance of viremia only in individuals who initially
      had an antibody response. We sought to characterize the immunological correlates
      of clearance in patients with acute hepatitis C and their sexual contacts. We
      prospectively determined CD4(+) and CD8(+) cytotoxic T-lymphocyte responses in
      index patients with acute HCV and their sexual contacts who developed acute
      infection, either with or without spontaneous clearance, as well as those
      contacts who never developed viremia. Responses were measured using proliferation
      and ELISpot assays for CD4(+) and CD8(+) responses. We demonstrate in this
      prospective study that cellular immune responses can develop in exposed but
      persistently aviremic and antibody-negative individuals as well as those
      individuals with spontaneous clearance of acute HCV. These findings lend further
      credence to the importance of cellular immune responses in recovery from HCV and
      suggest that low exposure to HCV may lead to development of HCV-specific immune
      responses without ongoing HCV replication. This finding has important
      implications for HCV vaccine and therapeutic development.

PMID- 15507611
TI  - Conditionally replicating adenoviruses kill tumor cells via a basic apoptotic
      machinery-independent mechanism that resembles necrosis-like programmed cell
      death.
AB  - Conditionally replicating adenoviruses (CRAds) represent a promising class of
      novel anticancer agents that are used for virotherapy. The E1ADelta24 mutation
      based viruses, Ad5-Delta24 [CRAd(E3-); E3 region deleted] and infectivity
      enhanced Ad5-Delta24RGD [CRAd(E3+)] have been shown to potently eradicate tumor
      cells. The presence of the E3 region in the latter virus is known to improve cell
      killing that can be attributed to the presence of the oncolysis-enhancing Ad
      death protein. The more precise mechanism by which CRAds kill tumor cells is
      unclear, and the role of the host cell apoptotic machinery in this process has
      been addressed only in a limited way. Here, we examine the role of several major
      apoptotic pathways in the CRAd-induced killing of non-small-cell lung cancer H460
      cells. As expected, CRAd(E3+) was more potent than CRAd(E3-). No evidence for the
      involvement of the p53-Bax apoptotic pathway was found. Western blot analyses
      demonstrated strong suppression of p53 expression and unchanged Bax levels during
      viral replication, and stable overexpression of human papillomavirus type 16-E6
      in H460 cells did not affect killing by both CRAds. CRAd activity was also not
      hampered by stable overexpression of anti-apoptotic Bcl2 or BclXL, and endogenous
      Bcl2/BclXL protein levels remained constant during the oncolytic cycle. Some
      evidence for caspase processing was obtained at late time points after infection;
      however, the inhibition of caspases by the X-linked inhibitor of apoptosis
      protein overexpression or cotreatment with zVAD-fmk did not inhibit CRAd
      dependent cell death. Analyses of several apoptotic features revealed no evidence
      for nuclear fragmentation or DNA laddering, although phosphatidylserine
      externalization was detected. We conclude that despite the known apoptosis
      modulating abilities of individual Ad proteins, Ad5-Delta24-based CRAds trigger
      necrosis-like cell death. In addition, we propose that deregulated apoptosis in
      cancer cells, a possible drug resistance mechanism, provides no barrier for CRAd
      efficacy.

PMID- 15507613
TI  - Uptake pathway of polyomavirus via ganglioside GD1a.
AB  - The pathway of entry of polyomavirus (Py) has been investigated with glycolipid
      deficient C6 cells and added ganglioside GD1a as a specific virus receptor.
      Unsupplemented C6 cells show a low basal level of infection but become highly
      infectable by Py following preincubation with the sialic acid-containing
      ganglioside GD1a (38). Addition of GD1a has no effect on the overall level of
      virus binding but mediates the internalization and transit of virus to the
      endoplasmic reticulum (ER). This pathway of entry is cholesterol and caveola
      dependent and requires intact microtubules as well as a dynamic state of the
      microfilament system. In contrast to vesicular transport of other cargo via
      glycolipids, Py particles do not appear to pass through the Golgi apparatus.
      Colcemid and brefeldin A block transport of the virus to the ER in GD1a
      supplemented cells and lead to accumulation of virus in a caveolin-1-containing
      environment. Several features distinguish the efficient GD1a-mediated pathway of
      virus uptake from the less-efficient pathway of basal infection in C6 cells.

PMID- 15507614
TI  - Entry of herpes simplex virus mediated by chimeric forms of nectin1 retargeted to
      endosomes or to lipid rafts occurs through acidic endosomes.
AB  - Herpes simplex virus (HSV) enters cells by fusion with target membranes, commonly
      the plasma membrane. In some cells, including CHO cells expressing the nectin1 or
      herpesvirus entry mediator receptors, entry occurs through an endocytic route. We
      report the following results. (i) When expressed in J cells, nectin1 and HVEM
      mediated a pathway of entry insensitive to endosome acidification inhibitors.
      (ii) A chimeric nectin1 receptor competent for endosomal uptake by fusion of the
      nectin1 ectodomain with the transmembrane sequence and cytoplasmic tail of the
      epidermal growth factor receptor (EGFR1) (nectin1-EGFR1) and chimeric nectin1
      sorted to lipid rafts by a glycosylphosphatidylinositol anchor mediated endocytic
      entry blocked by the early endosome inhibitor wortmannin and by the endosome
      acidification inhibitors bafilomycin and NH(4)Cl. (iii) Entry mediated by nectin1
      EGFR1 was selectively inhibited by AG1478, a tyrosine phosphorylation inhibitor
      that targets the EGFR1 cytoplasmic tail and blocks the signaling pathway that
      culminates in clathrin-dependent uptake of the receptor into endosomes. We draw
      the following conclusions. (i) The same receptor may initiate different routes of
      infection, depending on the cell in which it is expressed. Hence, the cell is a
      determinant that controls whether a given receptor initiates a plasma membrane or
      an endocytic route of entry. (ii) Receptors whose physiology involves uptake into
      endosomes or sorting to lipid rafts are suitable to serve as HSV receptors. (iii)
      Structural features of the receptors are additional determinants that control
      whether HSV entry occurs at the plasma membrane or at endosomes. These findings
      are relevant to studies of HSV retargeting to specific receptors.

PMID- 15507615
TI  - Multivesicular bodies as a platform for formation of the Marburg virus envelope.
AB  - The Marburg virus (MARV) envelope consists of a lipid membrane and two major
      proteins, the matrix protein VP40 and the glycoprotein GP. Both proteins use
      different intracellular transport pathways: GP utilizes the exocytotic pathway,
      while VP40 is transported through the retrograde late endosomal pathway. It is
      currently unknown where the proteins combine to form the viral envelope. In the
      present study, we identified the intracellular site where the two major envelope
      proteins of MARV come together as peripheral multivesicular bodies (MVBs). Upon
      coexpression with VP40, GP is redistributed from the trans-Golgi network into the
      VP40-containing MVBs. Ultrastructural analysis of MVBs suggested that they
      provide the platform for the formation of membrane structures that bud as virus
      like particles from the cell surface. The virus-like particles contain both VP40
      and GP. Single expression of GP also resulted in the release of particles, which
      are round or pleomorphic. Single expression of VP40 led to the release of
      filamentous structures that closely resemble viral particles and contain traces
      of endosomal marker proteins. This finding indicated a central role of VP40 in
      the formation of the filamentous structure of MARV particles, which is similar to
      the role of the related Ebola virusVP40. In MARV-infected cells, VP40 and GP are
      colocalized in peripheral MVBs as well. Moreover, intracellular budding of
      progeny virions into MVBs was frequently detected. Taken together, these results
      demonstrate an intracellular intersection between GP and VP40 pathways and
      suggest a crucial role of the late endosomal compartment for the formation of the
      viral envelope.

PMID- 15507616
TI  - CXCR4-dependent infection of CD8+, but not CD4+, lymphocytes by a primary human
      immunodeficiency virus type 1 isolate.
AB  - We recently isolated from an infant an X4-syncytium-inducing (SI) human
      immunodeficiency virus type 1 (HIV-1) variant (92US143-T8) that was able to
      infect CD8+ lymphocytes independently of CD4. Although it was CD4 independent,
      the 92US143-T8 isolate also maintained the ability to infect CD4+ cells. In the
      present study, we investigated the role of CXCR4 in the infection of CD4+ and
      CD8+ cells by this primary isolate. The expression of CXCR4 was down modulated in
      CD8+ lymphocytes after infection with the 93US143-T8 isolate. Infection of CD8+
      lymphocytes by the 93US143-T8 isolate was prevented by treatment with AMD3100, a
      specific antagonist for CXCR4, indicating CXCR4-dependent infection.
      Interestingly, AMD3100 treatment had no inhibitory role in the infection of
      purified CD4+ lymphocytes by the same isolate. Furthermore, AMD3100 treatment
      failed to prevent infection of known CD4+ CXCR4+ T-cell lines (MT-2 and CEM) by
      the 93US143-T8 isolate. In fact, virus replication in the CD4+ cells was often
      enhanced in the presence of AMD3100. Viruses produced from the infected CD4+
      cells in the presence of AMD3100 maintained an unchanged envelope genotype and an
      SI phenotype. For the first time, these results provide evidence of CXCR4
      dependent infection of CD8+ lymphocytes by a primary HIV-1 isolate. This study
      also shows a different mode of infection for the CD4+ and CD8+ lymphocytes by the
      same HIV-1 variant. Finally, our findings suggest that a more careful evaluation
      is necessary before the random use of AMD3100 as a new entry inhibitor in
      patients harboring SI HIV-1 strains.

PMID- 15507617
TI  - Adenovirus E3-6.7K protein is required in conjunction with the E3-RID protein
      complex for the internalization and degradation of TRAIL receptor 2.
AB  - Adenoviruses (Ads) encode several proteins within the early region 3 (E3)
      transcription unit that help protect infected cells from elimination by the
      immune system. Among these immunomodulatory proteins, the receptor
      internalization and degradation (RID) protein complex, which is composed of the
      RIDalpha (formerly E3-10.4K) and RIDbeta (formerly E3-14.5K) subunits, stimulates
      the internalization and degradation of certain members of the tumor necrosis
      factor (TNF) receptor superfamily, thus blocking apoptosis initiated by Fas and
      TNF-related apoptosis-inducing ligand (TRAIL). The experiments reported here show
      that TRAIL receptor 2 (TR2) is cleared from the cell surface in Ad-infected
      cells. Virus mutants containing deletions that span E3 were used to show that the
      RID and E3-6.7K proteins are both necessary for the internalization and
      degradation of TR2, whereas only the RID protein is required for TRAIL receptor 1
      downregulation. In addition, replication-defective Ad vectors that express
      individual E3 proteins were used to establish that the RID and E3-6.7K proteins
      are sufficient to clear TR2. These data demonstrate that E3-6.7K is an important
      component of the antiapoptosis arsenal encoded by the E3 transcription unit of
      subgroup C Ads.

PMID- 15507619
TI  - Postentry neutralization of adenovirus type 5 by an antihexon antibody.
AB  - Antibodies against hexon, the major coat protein of adenovirus (Ad), are an
      important component of the neutralizing activity in serum from naturally infected
      humans and experimentally infected animals. The mechanisms by which antihexon
      antibodies neutralize the virus have not been defined. As a model system, murine
      monoclonal antibodies raised against Ad type 5 (Ad5) were screened for antihexon
      binding and neutralization activity; one monoclonal antibody, designated 9C12,
      was selected for further characterization. The minimum ratio of 9C12 to Ad5
      required for neutralization was 240 antibody molecules per virus particle, or 1
      antibody per hexon trimer. Analysis of antibody-virus complexes by dynamic light
      scattering and negative-stain electron microscopy (EM) showed that the virus
      particles were coated with electron-dense material but not aggregated at
      neutralizing ratios. Cryo-EM image reconstruction of the antibody-virus complex
      showed that the surface of the virus particle was covered by a meshwork of 9C12
      antibody density, consistent with bivalent binding at multiple sites. Confocal
      analysis revealed that viral attachment, cell entry, and intracellular transport
      to the nuclear periphery still occur in the presence of neutralizing levels of
      9C12. A model is presented for neutralization of Ad by an antihexon antibody in
      which the hexon capsid is cross-linked by antibodies, thus preventing virus
      uncoating and nuclear entry of viral DNA.

PMID- 15507618
TI  - Dynamic chromatin boundaries delineate a latency control region of Epstein-Barr
      virus.
AB  - The oncogenic potential of latent Epstein-Barr virus (EBV) can be regulated by
      epigenetic factors controlling LMP1 and EBNA2 gene transcription. The EBV latency
      control region (LCR) constitutes approximately 12 kb of viral sequence spanning
      the divergent promoters of LMP1 and EBNA2 and encompasses the EBV latent
      replication origin OriP and RNA polymerase III-transcribed EBV-encoded RNA genes.
      We have used the chromatin immunoprecipitation assay to examine the chromatin
      architecture of the LCR in different types of EBV latency programs. We have found
      that histone H3 K4 methylation (H3mK4) was enriched throughout a large domain
      that extended from internal repeat 1 (IR1) to the terminal repeat in type III
      latency where EBNA2 and LMP1 genes are expressed. In type I latency where EBNA2
      and LMP1 genes are transcriptionally silent, the H3mK4 domain contracts and does
      not enter the EBNA2 or LMP1 promoters. In contrast, histone H3 K9 methylation
      (H3mK9), associated with silent heterochromatin, was enriched in the EBNA2 and
      LMP1 upstream control regions in type I but not type III cells. MTA [5'-deoxy
      5'(methylthio)adenosine], a pharmacological inhibitor of protein methylation,
      globally reduced histone H3mK4 and inhibited EBNA2 transcription in type III
      cells. 5'-Azacytidine, an inhibitor of DNA methylation that derepresses EBNA2
      transcription in type I latency, caused H3mK4 expansion and a corresponding loss
      of H3mK9 at IR1. The chromatin boundary protein and transcription repressor CCCTC
      binding factor was enriched at the EBNA2 transcription control region in type I
      but not type III cells. We also present evidence that OriP binding factors EBNA1
      and ORC2 can interact with sequences outside of OriP including a region within
      IR1 that may influence EBNA2 transcription status. These results indicate that
      types I and III latency programs have distinct histone methylation patterns in
      the LCR and suggest that chromatin architecture coordinates gene expression of
      LMP1 and EBNA2.

PMID- 15507620
TI  - Tracking fluorescence-labeled rabies virus: enhanced green fluorescent protein
      tagged phosphoprotein P supports virus gene expression and formation of
      infectious particles.
AB  - Rhabdoviruses such as rabies virus (RV) encode only five multifunctional proteins
      accomplishing viral gene expression and virus formation. The viral
      phosphoprotein, P, is a structural component of the viral ribonucleoprotein (RNP)
      complex and an essential cofactor for the viral RNA-dependent RNA polymerase. We
      show here that RV P fused to enhanced green fluorescent protein (eGFP) can
      substitute for P throughout the viral life cycle, allowing fluorescence labeling
      and tracking of RV RNPs under live cell conditions. To first assess the functions
      of P fusion constructs, a recombinant RV lacking the P gene, SAD DeltaP, was
      complemented in cell lines constitutively expressing eGFP-P or P-eGFP fusion
      proteins. P-eGFP supported the rapid accumulation of viral mRNAs but led to low
      infectious-virus titers, suggesting impairment of virus formation. In contrast,
      complementation with eGFP-P resulted in slower accumulation of mRNAs but similar
      infectious titers, suggesting interference with polymerase activity rather than
      with virus formation. Fluorescence microscopy allowed the detection of eGFP-P
      labeled extracellular virus particles and tracking of cell binding and
      temperature-dependent internalization into intracellular vesicles. Recombinant
      RVs expressing eGFP-P or an eGFP-P mutant lacking the binding site for dynein
      light chain 1 (DLC1) instead of P were used to track interaction with cellular
      proteins. In cells expressing a DsRed-labeled DLC1, colocalization of DLC1 with
      eGFP-P but not with the mutant P was observed. Fluorescent labeling of RV RNPs
      will allow further dissection of virus entry, replication, and egress under live
      cell conditions as well as cell interactions.

PMID- 15507621
TI  - CpG oligodeoxynucleotides block human immunodeficiency virus type 1 replication
      in human lymphoid tissue infected ex vivo.
AB  - Oligodeoxynucleotides (ODNs) with immunomodulatory motifs control a number of
      microbial infections in animal models, presumably by acting through toll-like
      receptor 9 (TLR9) to induce a number of cytokines (e.g., alpha interferon and
      tumor necrosis factor alpha). The immunomodulatory motif consists of unmethylated
      sequences of cytosine and guanosine (CpG motif). ODNs without CpG motifs do not
      trigger TLR9. We hypothesized that triggering of TLR9 generates a cellular
      environment unfavorable for human immunodeficiency virus (HIV) replication. We
      tested this hypothesis in human lymphocyte cultures and found that
      phosphorothioate-modified ODN CpG2006 (type B ODNs) inhibited HIV replication
      nearly completely and prevented the loss of CD4(+) T cells. ODNs CpG2216 and
      CpG10 (type A ODNs) were less effective. CpG2006 blocked HIV replication in
      purified CD4(+) T cells and T-cell lines; CpG10 was ineffective in this setting,
      indicating that type A ODNs may inhibit HIV replication in CD4(+) T-cell lines
      indirectly through a separate cell subset. However, control ODNs without CpG
      motifs also showed anti-HIV effects, indicating that these effects are
      nonspecific and not due to TLR9 triggering. The mechanism of action is not clear.
      CpG2006 and its control ODN blocked syncytium formation in a cell fusion-based
      assay, but CpG10, CpG2216, and their control ODNs did not. The latter types
      interfered with the HIV replication cycle during disassembly or reverse
      transcription. In contrast, CpG2006 and CpG2216 specifically induced cytokines
      critical to initiation of the innate immune response. In summary, the nonspecific
      anti-HIV activity of CpG ODNs, their ability to stimulate HIV replication in
      latently infected cells, potentially resulting in their elimination, and their
      documented ability to link the innate and adaptive immune responses make them
      attractive candidates for further study as anti-HIV drugs.

PMID- 15507622
TI  - Secretion of a TNFR:Fc fusion protein following pulmonary administration of
      pseudotyped adeno-associated virus vectors.
AB  - This study evaluated and compared delivery of the tumor necrosis factor alpha
      receptor (TNFR)-immunoglobulin G1 (IgG1) Fc fusion (TNFR:Fc) gene to the lung by
      single and repeat administrations of multiple pseudotyped adeno-associated virus
      (AAV) vectors as a means for achieving systemic distribution of the soluble
      TNFR:Fc protein. A single endotracheal administration of AAV[2/5]cytomegalovirus
      (CMV)-TNFR:Fc vector (containing the AAV2 inverted terminal repeats and AAV5
      capsid) to the rat lung resulted in long-term, high levels of serum TNFR:Fc
      protein that gradually declined over a period of 8 months. Endotracheal delivery
      of AAV[2/1]CMV-TNFR:Fc resulted in serum TNFR:Fc protein levels that were
      detectable for at least 4 months but were 10-fold lower than that of the AAV[2/5]
      vector. In contrast, secretion of the TNFR:Fc protein following pulmonary
      delivery of AAV[2/2]CMV-TNFR:Fc vector was very inefficient, and the protein was
      detected in the blood only when an airway epithelial cell-specific promoter,
      CC10, was substituted for the CMV enhancer/promoter to control transgene
      expression. In the context of AAV[2/5], the CC10 promoter was as efficient as CMV
      enhancer/promoter in generating similar levels of systemic TNFR:Fc protein,
      suggesting that this protein is secreted primarily from the airway epithelium. In
      mice, comparable long-term secretion of TNFR:Fc protein was demonstrated after
      AAV[2/2] and AAV[2/5] delivery, although the kinetics of transduction appeared to
      be different. All pseudotyped AAV vectors elicited serum anti-AAV capsid
      neutralizing antibody responses, but these did not prevent lung transduction and
      efficient secretion of TNFR:Fc protein to the circulation following
      readministration with AAV[2/5]. These results highlight the potential utility of
      AAV vectors containing serotype 5 capsid to deliver and redeliver genes of
      secreted proteins to the lung to achieve long-term systemic protein expression.

PMID- 15507623
TI  - Role of the PDZ domain-binding motif of the oncoprotein E6 in the pathogenesis of
      human papillomavirus type 31.
AB  - A number of PDZ domain-containing proteins have been identified as binding
      partners for the oncoprotein E6 of the high-risk type human papillomaviruses
      (HPVs). These include hDlg, hScrib, MAGI-1, MAGI-2, MAGI-3, and MUPP1. The PDZ
      domain-binding motif (-X-T-X-V) at the carboxy terminus of E6 is essential for
      targeting PDZ proteins for proteasomal degradation. The presence of this motif
      only in the high-risk HPVs suggests its possible role in HPV-induced oncogenesis.
      To investigate the role of the PDZ domain-binding motif of E6 in the HPV life
      cycle, two mutant HPV31 genomes were constructed: E6ValDelta, with a deletion of
      the last amino acid residue of E6 (valine), and E6ETQVDelta, with a deletion of
      the entire PDZ domain-binding motif of E6 (ETQV). Three human foreskin
      keratinocyte (HFK) cell lines were established which maintained transfected wild
      type HPV31 or either of two mutant genomes. Cells containing either of two mutant
      genomes were significantly retarded in their growth rates and reduced in their
      viral copy numbers compared to those transfected with wild-type genomes. Western
      analysis did not reveal any significant changes in the levels of PDZ proteins
      following stable transfection of any HPV31 genomes into HFKs. Although the
      E6ETQVDelta-transfected HFKs exhibited a pattern of morphological differentiation
      that appeared different from the HPV31 wild-type-transfected HFKs in organotypic
      raft cultures, immunohistochemical analysis failed to identify substantial
      changes in the differentiation-dependent membrane localization of hDlg proteins.
      These results suggest that binding of E6 to PDZ proteins modulates the early
      viral functions such as proliferation and maintenance of the viral copy number in
      undifferentiated cells.

PMID- 15507624
TI  - Role of murine leukemia virus nucleocapsid protein in virus assembly.
AB  - The retroviral nucleocapsid protein (NC) originates by cleavage of the Gag
      polyprotein. It is highly basic and contains one or two zinc fingers. Mutations
      in either the basic residues or the zinc fingers can affect several events of the
      virus life cycle. They frequently prevent the specific packaging of the viral
      RNA, affect reverse transcription, and impair virion assembly. In this work, we
      explore the role of NC in murine leukemia virus (MLV) particle assembly and
      release. A panel of NC mutants, including mutants of the zinc finger and of a
      basic region, as well as truncations of the NC domain of Gag, were studied.
      Several of these mutations dramatically reduce the release of virus particles. A
      mutant completely lacking the NC domain is apparently incapable of assembling
      into particles, although its Gag protein is still targeted to the plasma
      membrane. By electron microscopy on thin sections of virus-producing cells, we
      observed that some NC mutants exhibit various stages of budding defects at the
      plasma membrane and have aberrant particle morphology; electron micrographs of
      cells expressing some of these mutants are strikingly similar to those of cells
      expressing "late-domain" mutants. However, the defects of NC mutants with respect
      to virus release and infectivity could be complemented by an MLV lacking the p12
      domain. Therefore, the functions of NC in virus budding and infectivity are
      completely distinct from viral late-domain function.

PMID- 15507625
TI  - Expression of human immunodeficiency virus type 1 gag modulates ligand-induced
      downregulation of EGF receptor.
AB  - Many enveloped viruses use the ESCRT proteins of the cellular vacuolar protein
      sorting pathway for efficient egress from the cell. Recruitment of the ESCRT
      proteins by human immunodeficiency virus type 1 (HIV-1) Gag is required for HIV-1
      particle budding and egress. ESCRT proteins normally function at endosomal
      membranes, where they facilitate the downregulation of mitogen-activated
      receptors such as EGF receptor (EGFR) through multivesicular body biogenesis. It
      is not known whether the Gag-mediated recruitment of ESCRT proteins functionally
      depletes the pool of these molecules that is available for the downregulation of
      EGFR. Here we show that the expression of HIV-1 Gag decreases the rate of EGFR
      downregulation, as assessed by decreases in the rates of (125)I-EGF and EGFR
      degradation. The effect of Gag was dependent on the presence of the TSG101
      binding motif (PTAP) within the Gag C-terminal p6 domain. Cells expressing HIV-1
      Gag retained more EGFR in late endosomes. This effect occurred when Gag was
      expressed alone from a heterologous promoter and when Gag expression was driven
      by the HIV-1 long terminal repeat within pHXB2DeltaBalD25S, a noninfectious
      lentiviral vector. Gag-expressing cells exhibited higher levels of activated
      mitogen-activated protein kinase for longer times after EGF addition than did
      cells that did not express HIV-1 Gag. These results indicate that HIV-1 Gag can
      impinge upon the functioning of the cellular vacuolar protein sorting pathway and
      reveal yet another facet of the intricate effects of HIV-1 infection on host cell
      physiology.

PMID- 15507626
TI  - Perforin and Fas act together in the induction of apoptosis, and both are
      critical in the clearance of lymphocytic choriomeningitis virus infection.
AB  - In this report we questioned the current view that the two principal cytotoxic
      pathways, the exocytosis and the Fas ligand (FasL)/Fas-mediated pathway, have
      largely nonoverlapping biological roles. For this purpose we have analyzed the
      response of mice that lack Fas as well as granzyme A (gzmA) and gzmB (FasxgzmAxB(
      /-)) to infection with lymphocytic choriomeningitis virus (LCMV). We show that
      FasxgzmAxB(-/-) mice, in contrast to B6, Fas(-/-), and gzmAxB(-/-) mice, do not
      recover from a primary infection with LCMV, in spite of the expression of
      comparable numbers of LCMV-immune and gamma interferon-producing cytotoxic T
      lymphocytes (CTL) in all mouse strains tested. Ex vivo-derived FasxgzmAxB(-/-)
      CTL lacked nucleolytic activity and expressed reduced cytolytic activity compared
      to B6 and Fas(-/-) CTL. Furthermore, virus-immune CTL with functional FasL and
      perforin (gzmAxB(-/-)) are more potent in causing target cell apoptosis in vitro
      than those expressing FasL alone (perfxgzmAxB(-/-)). This synergistic effect of
      perforin on Fas-mediated nucleolysis of target cells is indicated by the fact
      that, compared to perfxgzmAxB(-/-) CTL, gzmAxB(-/-) CTL induced (i) an
      accelerated decrease in mitochondrial transmembrane potential, (ii) increased
      generation of reactive oxygen species, and (iii) accelerated phosphatidylserine
      exposure on plasma membranes. We conclude that perforin does not mediate recovery
      from LCMV by itself but plays a vital role in both gzmA/B and FasL/Fas-mediated
      CTL activities, including apoptosis and control of viral infections.

PMID- 15507627
TI  - Functions of the C-terminal domain of varicella-zoster virus glycoprotein E in
      viral replication in vitro and skin and T-cell tropism in vivo.
AB  - Varicella-zoster virus (VZV) glycoprotein E (gE) is essential for VZV
      replication. To further analyze the functions of gE in VZV replication, a full
      deletion and point mutations were made in the 62-amino-acid (aa) C-terminal
      domain. Targeted mutations were introduced in YAGL (aa 582 to 585), which
      mediates gE endocytosis, AYRV (aa 568 to 571), which targets gE to the trans
      Golgi network (TGN), and SSTT, an "acid cluster" comprising a phosphorylation
      motif (aa 588 to 601). Substitutions Y582G in YAGL, Y569A in AYRV, and S593A,
      S595A, T596A, and T598A in SSTT were introduced into the viral genome by using
      VZV cosmids. These experiments demonstrated a hierarchy in the contributions of
      these C-terminal motifs to VZV replication and virulence. Deletion of the gE C
      terminus and mutation of YAGL were lethal for VZV replication in vitro. Mutations
      of AYRV and SSTT were compatible with recovery of VZV, but the AYRV mutation
      resulted in rapid virus spread in vitro and the SSTT mutation resulted in higher
      virus titers than were observed for the parental rOka strain. When the rOka-gE
      AYRV and rOka-gE-SSTT mutants were evaluated in skin and T-cell xenografts in
      SCIDhu mice, interference with TGN targeting was associated with substantial
      attenuation, especially in skin, whereas the SSTT mutation did not alter VZV
      infectivity in vivo. These results provide the first information about how
      targeted mutations of this essential VZV glycoprotein affect viral replication in
      vitro and VZV virulence in dermal and epidermal cells and T cells within intact
      tissue microenvironments in vivo.

PMID- 15507629
TI  - Emergence of a drug-dependent human immunodeficiency virus type 1 variant during
      therapy with the T20 fusion inhibitor.
AB  - The fusion inhibitor T20 belongs to a new class of anti-human immunodeficiency
      virus type 1 (HIV-1) drugs designed to block entry of the virus into the host
      cell. However, the success of T20 has met with the inevitable emergence of drug
      resistant HIV-1 variants. We describe an evolutionary pathway taken by HIV-1 to
      escape from the selective pressure of T20 in a treated patient. Besides the
      appearance of T20-resistant variants, we report for the first time the emergence
      of drug-dependent viruses with mutations in both the HR1 and HR2 domains of
      envelope glycoprotein 41. We propose a mechanistic model for the dependence of
      HIV-1 entry on the T20 peptide. The T20-dependent mutant is more prone to undergo
      the conformational switch that results in the formation of the fusogenic six
      helix bundle structure in gp41. A premature switch will generate nonfunctional
      envelope glycoproteins (dead spikes) on the surface of the virion, and T20
      prevents this abortive event by acting as a safety pin that preserves an earlier
      prefusion conformation.

PMID- 15507628
TI  - Inhibition of interferon-mediated antiviral activity by murine gammaherpesvirus
      68 latency-associated M2 protein.
AB  - Upon viral infection, the major defense mounted by the host immune system is the
      activation of the interferon (IFN)-mediated antiviral pathway. In order to
      complete their life cycle, viruses that are obligatory intracellular parasites
      must modulate the host IFN-mediated immune response. Murine gammaherpesvirus 68
      (gammaHV68) infects a wide range of cell types and establishes latent infections
      in mice. Here we demonstrate that the gammaHV68 latency-associated M2 protein has
      a cell-type-dependent localization pattern: M2 is present in the cytoplasm and
      plasma membrane in lymphocytes, whereas it is present primarily in the nucleus in
      epithelial and fibroblast cells. A mutational analysis indicated that the
      internal positively charged amino acids of M2 are required for its nuclear
      localization in fibroblasts. Purification of the M2 complex showed that M2
      specifically interacts with the cellular p32 acidic protein through its central
      positively charged region and that this interaction recruits the cellular p32
      protein to the nucleus in fibroblasts. Regardless of its localization, M2
      expression effectively induced the downregulation of STAT1 and/or STAT2 in both
      A20 B lymphocytes and NIH 3T3 fibroblasts, resulting in the inhibition of IFN
      alpha/beta- and IFN-gamma-mediated transcriptional activation. Finally, the M2
      interaction with the p32 protein appeared to contribute to its ability to inhibit
      IFN-mediated transcriptional activation. These results indicate that gammaHV68
      harbors a latency-associated M2 gene that antagonizes IFN-mediated host innate
      immunity and thus could play an important role in the establishment and
      maintenance of viral latency in infected animals.

PMID- 15507630
TI  - Distinct human immunodeficiency virus type 1 subtype A virus circulating in West
      Africa: sub-subtype A3.
AB  - Phylogenetic analyses demonstrate significant diversity in worldwide circulating
      strains of human immunodeficiency virus type 1 (HIV-1). Detailed studies have
      revealed a complex pattern of intersubtype recombinations, as well as evidence of
      sub-subtypes circulating in various populations. In this study, we characterized
      an HIV-1 strain that had previously been identified as a distinct subcluster
      within the subtype A radiation based on partial sequence data. These viruses were
      of particular interest given that we recently found that their prevalence was
      significantly higher in dually infected individuals compared to women who were
      singly infected with HIV-1. Five viruses isolated from commercial sex workers in
      Dakar, Senegal, were full-length PCR amplified and sequenced. Phylogenetic
      analyses indicated that, whereas three of these viruses were closely related and
      clustered overall within the HIV-1 subtype A radiation, they were distinct from
      previously characterized sub-subtype A1 and A2 viruses. The clustering pattern
      was maintained in the individual gag, pol, and env regions of the genome.
      Distance calculations between these viruses, which we termed A3, and other
      reference sub-subtype A1 and A2 viruses fell in the range of distances between
      previously characterized sub-subtype groups. In addition, we found evidence of
      two A3-containing recombinants in our cohort. These recombinants are mosaics
      composed of sequence from both sub-subtype A3 and CRF02_AG, the major circulating
      recombinant form in this West African population. Based on phylogenetic analyses,
      we propose that the group of viruses found in the Dakar sex worker cohort,
      previously referred to as HIV-1 A subcluster 2, be referred to as HIV-1 sub
      subtype A3.

PMID- 15507631
TI  - Structural basis for coevolution of a human immunodeficiency virus type 1
      nucleocapsid-p1 cleavage site with a V82A drug-resistant mutation in viral
      protease.
AB  - Maturation of human immunodeficiency virus (HIV) depends on the processing of Gag
      and Pol polyproteins by the viral protease, making this enzyme a prime target for
      anti-HIV therapy. Among the protease substrates, the nucleocapsid-p1 (NC-p1)
      sequence is the least homologous, and its cleavage is the rate-determining step
      in viral maturation. In the other substrates of HIV-1 protease, P1 is usually
      either a hydrophobic or an aromatic residue, and P2 is usually a branched
      residue. NC-p1, however, contains Asn at P1 and Ala at P2. In response to the
      V82A drug-resistant protease mutation, the P2 alanine of NC-p1 mutates to valine
      (AP2V). To provide a structural rationale for HIV-1 protease binding to the NC-p1
      cleavage site, we solved the crystal structures of inactive (D25N) WT and V82A
      HIV-1 proteases in complex with their respective WT and AP2V mutant NC-p1
      substrates. Overall, the WT NC-p1 peptide binds HIV-1 protease less optimally
      than the AP2V mutant, as indicated by the presence of fewer hydrogen bonds and
      fewer van der Waals contacts. AlaP2 does not fill the P2 pocket completely;
      PheP1' makes van der Waals interactions with Val82 that are lost with the V82A
      protease mutation. This loss is compensated by the AP2V mutation, which reorients
      the peptide to a conformation more similar to that observed in other substrate
      protease complexes. Thus, the mutant substrate not only binds the mutant protease
      more optimally but also reveals the interdependency between the P1' and P2
      substrate sites. This structural interdependency results from coevolution of the
      substrate with the viral protease.

PMID- 15507632
TI  - Molecular epidemiology of human immunodeficiency virus type 1 sub-subtype A3 in
      Senegal from 1988 to 2001.
AB  - The global human immunodeficiency virus (HIV)epidemic is characterized by
      significant genetic diversity in circulating viruses. We have recently
      characterized a group of viruses that form a distinct sub-subtype within the
      subtype A radiation, which we have designated HIV type 1 (HIV-1) sub-subtype A,
      circulating in West Africa. A prospective study of a cohort of female sex workers
      (FSW) in Dakar, Senegal over an 18-year period indicated that an A3-specific
      sequence in the C2-V3 region of the env gene was found in 46 HIV-1-infected
      women. HIV-1 sub-subtype A3 appeared in the FSW population as early as 1988 and
      continued to be transmitted as of 2001. We also found that HIV-1 A3 is not
      confined to the FSW cohort in Senegal but is also circulating in the general
      population in Dakar. Furthermore, analyses of viral sequences from a few other
      West and Central African countries also demonstrated evidence of HIV-1 A3
      sequence in isolates from HIV-1-infected people in Ivory Coast, Nigeria, Niger,
      Guinea Bissau, Benin, and Equatorial Guinea. Overall, because of the evidence of
      sub-subtype A3 in the general population in Senegal, as well as in a few
      neighboring West and Central African countries, along with the increasing
      incidence of infection with A3-containing viruses in the Dakar high-risk FSW
      population, we feel that HIV-1 sub-subtype A3 viruses are important to
      distinguish and monitor.

PMID- 15507633
TI  - Novel origin of the 1918 pandemic influenza virus nucleoprotein gene.
AB  - The nucleoprotein (NP) gene of the 1918 pandemic influenza A virus has been
      amplified and sequenced from archival material. The NP gene is known to be
      involved in many aspects of viral function and to interact with host proteins,
      thereby playing a role in host specificity. The 1918 NP amino acid sequence
      differs at only six amino acids from avian consensus sequences, consistent with
      reassortment from an avian source shortly before 1918. However, the nucleotide
      sequence of the 1918 NP gene has more than 170 differences from avian strain
      consensus sequences, suggesting substantial evolutionary distance from known
      avian strain sequences. Both the gene and protein sequences of the 1918 NP fall
      within the mammalian clade upon phylogenetic analysis. The evolutionary distance
      of the 1918 NP sequences from avian and mammalian strain sequences is examined,
      using several different parameters. The results suggest that the 1918 strain did
      not retain the previously circulating human NP. Nor is it likely to have obtained
      its NP by reassortment with an avian strain similar to those now characterized.
      The results are consistent with the existence of a currently unknown host for
      influenza, with an NP similar to current avian strain NPs at the amino acid level
      but with many synonymous nucleotide differences, suggesting evolutionary
      isolation from the currently characterized avian influenza virus gene pool.

PMID- 15507634
TI  - Modified vaccinia virus Ankara immunization protects against lethal challenge
      with recombinant vaccinia virus expressing murine interleukin-4.
AB  - Recent events have raised concern over the use of pathogens, including variola
      virus, as biological weapons. Vaccination with Dryvax is associated with serious
      side effects and is contraindicated for many people, and the development of a
      safer effective smallpox vaccine is necessary. We evaluated an attenuated
      vaccinia virus, modified vaccinia virus Ankara (MVA), by use of a murine model to
      determine its efficacy against an intradermal (i.d.) or intranasal (i.n.)
      challenge with vaccinia virus (vSC8) or a recombinant vaccinia virus expressing
      murine interleukin-4 that exhibits enhanced virulence (vSC8-mIL4). After an i.d.
      challenge, 15 of 16 mice who were inoculated with phosphate-buffered saline
      developed lesions, one dose of intramuscularly administered MVA was partially
      protective (3 of 16 mice developed lesions), and the administration of two or
      three doses of MVA was completely protective (0 of 16 mice developed lesions). In
      unimmunized mice, an i.n. challenge with vSC8 caused a significant but self
      limited illness, while vSC8-mIL4 resulted in lethal infections. Immunization with
      one or two doses of MVA prevented illness and reduced virus titers in mice who
      were challenged with either vSC8 or vSC8-mIL4. MVA induced a dose-related
      neutralizing antibody and vaccinia virus-specific CD8+-T-cell response. Mice
      immunized with MVA were fully protected from a low-dose vSC8-mIL4 challenge
      despite a depletion of CD4+ cells, CD8+ cells, or both T-cell subsets or an
      antibody deficiency. CD4+- or CD8+-T-cell depletion reduced the protection
      against a high-dose vSC8-mIL4 challenge, and the depletion of both T-cell subsets
      was associated with severe illness and higher vaccinia virus titers. Thus, MVA
      induces broad humoral and cellular immune responses that can independently
      protect against a molecularly modified lethal poxvirus challenge in mice. These
      data support the continued development of MVA as an alternative candidate vaccine
      for smallpox.

PMID- 15507635
TI  - Transition from acute to persistent Theiler's virus infection requires active
      viral replication that drives proinflammatory cytokine expression and chronic
      demyelinating disease.
AB  - The dynamics of Theiler's murine encephalomyelitis virus (TMEV) RNA replication
      in the central nervous systems of susceptible and resistant strains of mice were
      examined by quantitative real-time reverse transcription-PCR and were found to
      correlate with host immune responses. During the acute phase of infection in both
      susceptible and resistant mice, levels of viral replication were high in the
      brain and brain stem, while levels of viral genome equivalents were 10- to 100
      fold lower in the spinal cord. In the brain, viral RNA replication decreased
      after a peak at 5 days postinfection (p.i.), in parallel with the appearance of
      virus-specific antibody responses; however, by 15 days p.i., viral RNA levels
      began to increase in the spinal cords of susceptible mice. During the transition
      to and the persistent phase of infection, the numbers of viral genome equivalents
      in the spinal cord varied substantially for individual mice, but high levels were
      consistently associated with high levels of proinflammatory Th1 cytokine and
      chemokine mRNAs. Moreover, a large number of viral genome equivalents and high
      proinflammatory cytokine mRNA levels in spinal cords were only observed for
      susceptible SJL/J mice who developed demyelinating disease. These results suggest
      that TMEV persistence requires active viral replication beginning about day 11
      p.i. and that active viral replication with high viral genome loads leads to
      increased levels of Th1 cytokines that drive disease progression in infected
      mice.

PMID- 15507636
TI  - The VP6 protein of rotavirus interacts with a large fraction of human naive B
      cells via surface immunoglobulins.
AB  - Immunity to human group A rotavirus (RV), a major cause of viral gastroenteritis
      in infants, involves B lymphocytes that provide RV-specific antibodies.
      Additionally, some arguments suggest that naive B cells could be implicated in
      the first steps of the immune response against RV. The aim of our study was to
      analyze the interaction of VP6 and VP7 RV capsid proteins with human B cells
      depending on the immune status of the individual, i.e., naive or RV experienced.
      For this purpose, a two-color virus-like particle flow cytometry assay was
      devised to evaluate the blood B-lymphocyte reactivity to VP6 and VP7 proteins
      from healthy RV-exposed adults, recently infected infants, and neonates at birth.
      Both VP6 and VP7 interactions with B cells were mediated by surface
      immunoglobulins and probably by their Fab portions. VP7-reactive B lymphocytes
      were mainly detected from RV-experienced patients and almost exclusively in the
      CD27-positive memory cell fraction. Conversely, VP6-reactive B lymphocytes were
      detected at similar and high frequencies in adult, infant, and neonate samples.
      In adult samples, VP6 reacted with about 2% of the CD27-negative (CD27(neg))
      naive B cells. These results demonstrated that the VP6 RV protein interacted with
      a large fraction of naive B lymphocytes from both adults and neonates. We propose
      that naive B cell-VP6 interaction might influence the strength and quality of the
      acquired immune response and should be considered for elaborating RV vaccine
      strategies.

PMID- 15507637
TI  - ChimeriVax-West Nile virus live-attenuated vaccine: preclinical evaluation of
      safety, immunogenicity, and efficacy.
AB  - The availability of ChimeriVax vaccine technology for delivery of flavivirus
      protective antigens at the time West Nile (WN) virus was first detected in North
      America in 1999 contributed to the rapid development of the vaccine candidate
      against WN virus described here. ChimeriVax-Japanese encephalitis (JE), the first
      live- attenuated vaccine developed with this technology has successfully
      undergone phase I and II clinical trials. The ChimeriVax technology utilizes
      yellow fever virus (YF) 17D vaccine strain capsid and nonstructural genes to
      deliver the envelope gene of other flaviviruses as live-attenuated chimeric
      viruses. Amino acid sequence homology between the envelope protein (E) of JE and
      WN viruses facilitated targeting attenuating mutation sites to develop the WN
      vaccine. Here we discuss preclinical studies with the ChimeriVax-WN virus in mice
      and macaques. ChimeriVax-WN virus vaccine is less neurovirulent than the
      commercial YF 17D vaccine in mice and nonhuman primates. Attenuation of the virus
      is determined by the chimeric nature of the construct containing attenuating
      mutations in the YF 17D virus backbone and three point mutations introduced to
      alter residues 107, 316, and 440 in the WN virus E protein gene. The safety,
      immunogenicity, and efficacy of the ChimeriVax-WN(02) vaccine in the macaque
      model indicate the vaccine candidate is expected to be safe and immunogenic for
      humans.

PMID- 15507638
TI  - The herpes simplex virus type 1 latency-associated transcript (LAT) enhancer/rcr
      is hyperacetylated during latency independently of LAT transcription.
AB  - During herpes simplex virus type 1 (HSV-1) latency, only one region of the viral
      genome is actively transcribed: the region encoding the latency-associated
      transcript (LAT). A previous study demonstrated that during latency the LAT
      promoter is hyperacetylated at histone H3 (K9, K14) relative to lytic genes
      examined. In the present study, we examine the acetylation profile of regions
      downstream of the LAT promoter during a latent infection of murine dorsal root
      ganglia. These analyses revealed the following: (i) the region of the genome
      containing the 5' exon of the LAT primary transcript was at least as enriched in
      acetylated H3 as the LAT promoter, and (ii) the region of hyperacetylation does
      not extend to the ICP0 promoter. In order to assess the contribution of LAT
      transcription to the acetylation of the 5' exon region, the acetylation profile
      of KOS/29, a recombinant with a deletion of the LAT promoter, was examined. The
      region containing the 5' exon of KOS/29 was hyperacetylated relative to lytic
      gene regions in the absence of detectable LAT transcription. These results
      indicate that the region containing the 5' exon of LAT, known to contain enhancer
      activities and to be critical for induced reactivation (rcr), exists in a
      chromatin structure during latency that is distinct from other lytic gene
      regions. This result suggests a role for the 5' exon LAT enhancer region as a cis
      acting regulator of transcription that maintains a transcriptionally permissive
      chromatin domain in the HSV-1 latent episome.

PMID- 15507639
TI  - Granzymes and caspase 3 play important roles in control of gammaherpesvirus
      latency.
AB  - Gammaherpesviruses can establish lifelong latent infections in lymphoid cells of
      their hosts despite active antiviral immunity. Identification of the immune
      mechanisms which regulate gammaherpesvirus latent infection is therefore
      essential for understanding how gammaherpesviruses persist for the lifetime of
      their host. Recently, an individual with chronic active Epstein-Barr virus
      infection was found to have mutations in perforin, and studies using murine
      gammaherpesvirus 68 (gammaHV68) as a small-animal model for gammaherpesvirus
      infection have similarly revealed a critical role for perforin in regulating
      latent infection. These results suggest involvement of the perforin/granzyme
      granule exocytosis pathway in immune regulation of gammaherpesvirus latent
      infection. In this study, we examined gammaHV68 infection of knockout mice to
      identify specific molecules within the perforin/granzyme pathway which are
      essential for regulating gammaherpesvirus latent infection. We show that
      granzymes A and B and the granzyme B substrate, caspase 3, are important for
      regulating gammaHV68 latent infection. Interestingly, we show for the first time
      that orphan granzymes encoded in the granzyme B gene cluster are also critical
      for regulating viral infection. The requirement for specific granzymes differs
      for early versus late forms of latent infection. These data indicate that
      different granzymes play important and distinct roles in regulating latent
      gammaherpesvirus infection.

PMID- 15507640
TI  - A cyclooxygenase-2 homologue encoded by rhesus cytomegalovirus is a determinant
      for endothelial cell tropism.
AB  - Cyclooxygenase-2 (COX-2) is a cellular enzyme in the eicosanoid synthetic pathway
      that mediates the synthesis of prostaglandins from arachidonic acid. The
      eicosanoids function as critical regulators of a number of cellular processes,
      including the acute and chronic inflammatory response, hemostasis, and the innate
      immune response. Human cytomegalovirus (HCMV), which does not encode a viral COX
      2 isoform, has been shown to induce cellular COX-2 expression. Importantly,
      although the precise role of COX-2 in CMV replication is unknown, COX-2 induction
      was shown to be critical for normal HCMV replication. In an earlier study, we
      identified an open reading frame (Rh10) within the rhesus cytomegalovirus (RhCMV)
      genome that encoded a putative protein (designated vCOX-2) with high homology to
      cellular COX-2. In the current study, we show that vCOX-2 is expressed with early
      gene kinetics during RhCMV infection, resulting in production of a 70-kDa
      protein. Consistent with the expression of a viral COX-2 isoform, cellular COX-2
      expression was not induced during RhCMV infection. Finally, analysis of growth of
      recombinant RhCMV with vCOX-2 deleted identified vCOX-2 as a critical determinant
      for replication in endothelial cells.

PMID- 15507641
TI  - Murine T cells potently restrict human immunodeficiency virus infection.
AB  - Development of a mouse model for human immunodeficiency virus type 1 (HIV-1)
      infection has advanced through the progressive identification of host cell
      factors required for HIV-1 replication. Murine cells lack HIV-1 receptor
      molecules, do not support efficient viral gene expression, and lack factors
      necessary for the assembly and release of virions. Many of these blocks have been
      described using mouse fibroblast cell lines. Here we identify a postentry block
      to HIV-1 infection in mouse T-cell lines that has not been detected in mouse
      fibroblasts. While murine fibroblastic lines are comparable to human T-cell lines
      in permissivity to HIV-1 transduction, infection of murine T cells is 100-fold
      less efficient. Virus entry occurs efficiently in murine T cells. However,
      reduced efficiency of the completion of reverse transcription and nuclear
      transfer of the viral preintegration complex are observed. Although this block
      has similarities to the restriction of murine retroviruses by Fv1, there is no
      correlation of HIV-1 susceptibility with cellular Fv1 genotypes. In addition, the
      block to HIV-1 infection in murine T-cell lines cannot be saturated by a high
      virus dose. Further studies of this newly identified block may lend insight into
      the early events of retroviral replication and reveal new targets for
      antiretroviral interventions.

PMID- 15507642
TI  - Coxsackievirus group B type 3 infection upregulates expression of monocyte
      chemoattractant protein 1 in cardiac myocytes, which leads to enhanced migration
      of mononuclear cells in viral myocarditis.
AB  - Coxsackievirus group B type 3 (CVB3) is an important cause of viral myocarditis.
      The infiltration of mononuclear cells into the myocardial tissue is one of the
      key events in viral myocarditis. Immediately after CVB3 infects the heart, the
      expression of chemokine(s) by infected myocardial cells may be the first trigger
      for inflammatory infiltration and immune response. However, it is unknown whether
      CVB3 can induce the chemokine expression in cardiac myocytes. Monocyte
      chemoattractant protein 1 (MCP-1) is a potent chemokine that stimulates the
      migration of mononuclear cells. The objective of the present study was to
      investigate the effect of CVB3 infection on MCP-1 expression in murine cardiac
      myocytes and the role of MCP-1 in migration of mononuclear cells in viral
      myocarditis. Our results showed that the expression of MCP-1 was significantly
      increased in cardiac myocytes after wild-type CVB3 infection in a time- and dose
      dependent manner, which resulted in enhanced migration of mononuclear cells in
      mice with viral myocarditis. The migration of mononuclear cells was partially
      abolished by antibodies specific for MCP-1 in vivo and in vitro. Administration
      of anti-MCP-1 antibody prevented infiltration of mononuclear cells bearing the
      MCP-1 receptor CCR2 in mice with viral myocarditis. Infection by UV-irradiated
      CVB3 induced rapid and transient expression of MCP-1 in cardiac myocytes. In
      conclusion, our results indicate that CVB3 infection stimulates the expression of
      MCP-1 in myocardial cells, which subsequently leads to migration of mononuclear
      cells in viral myocarditis.

PMID- 15507643
TI  - Generation of synthetic severe acute respiratory syndrome coronavirus
      pseudoparticles: implications for assembly and vaccine production.
AB  - The recently emerged severe acute respiratory syndrome coronavirus (SARS-CoV)
      contains four structural genes, two replicase-transcriptase open reading frames,
      and more than five potential genes of unknown function. Despite this relative
      simplicity, the molecular regulation of SARS-CoV replication and assembly is not
      understood. Here, we report that two viral genes, encoding the SARS-CoV membrane
      (M) and nucleocapsid (N) proteins, are necessary and sufficient for formation of
      virus-like particles. Expression vectors encoding these two proteins were
      synthesized by using preferred human codons. When M and N expression plasmids
      were cotransfected into human 293 renal epithelial cells, pseudoparticles formed
      readily. The addition of a third gene, encoding the spike (S) glycoprotein,
      facilitated budding of particles that contained a corona-like halo resembling
      SARS-CoV when examined by transmission electron microscopy, with a buoyant
      density characteristic of coronaviruses. Specific biochemical interactions of
      these proteins were also shown in vitro. The S, M, and N proteins of the SARS-CoV
      are, therefore, necessary and sufficient for pseudovirus assembly. These findings
      advance the understanding of the morphogenesis of SARS-CoV and enable the
      generation of safe, conformational mimetics of the SARS virus that may facilitate
      the development of vaccines and antiviral drugs.

PMID- 15507645
TI  - Functional genomics analysis of Singapore grouper iridovirus: complete sequence
      determination and proteomic analysis.
AB  - Here we report the complete genome sequence of Singapore grouper iridovirus
      (SGIV). Sequencing of the random shotgun and restriction endonuclease genomic
      libraries showed that the entire SGIV genome consists of 140,131 nucleotide bp.
      One hundred sixty-two open reading frames (ORFs) from the sense and antisense DNA
      strands, coding for lengths varying from 41 to 1,268 amino acids, were
      identified. Computer-assisted analyses of the deduced amino acid sequences
      revealed that 77 of the ORFs exhibited homologies to known virus genes, 23 of
      which matched functional iridovirus proteins. Forty-two putative conserved
      domains or signatures were detected in the National Center for Biotechnology
      Information CD-Search database and PROSITE database. An assortment of enzyme
      activities involved in DNA replication, transcription, nucleotide metabolism,
      cell signaling, etc., were identified. Viruses were cultured on a cell line
      derived from the embryonated egg of the grouper Epinephelus tauvina, isolated,
      and purified by sucrose gradient ultracentrifugation. The protein extract from
      the purified virions was analyzed by polyacrylamide gel electrophoresis followed
      by in-gel digestion of protein bands. Matrix-assisted laser desorption ionization
      time of flight mass spectrometry and database searching led to identification of
      26 proteins. Twenty of these represented novel or previously unidentified genes,
      which were further confirmed by reverse transcription-PCR (RT-PCR) and DNA
      sequencing of their respective RT-PCR products.

PMID- 15507644
TI  - ORC, MCM, and histone hyperacetylation at the Kaposi's sarcoma-associated
      herpesvirus latent replication origin.
AB  - The viral genome of Kaposi's sarcoma-associated herpesvirus (KSHV) persists as an
      extrachromosomal plasmid in latently infected cells. The KSHV latency-associated
      nuclear antigen (LANA) stimulates plasmid maintenance and DNA replication by
      binding to an approximately 150-bp region within the viral terminal repeats (TR).
      We have used chromatin immunoprecipitation assays to demonstrate that LANA binds
      specifically to the replication origin sequence within the KSHV TR in latently
      infected cells. The latent replication origin within the TR was also bound by
      LANA-associated proteins CBP, double-bromodomain-containing protein 2 (BRD2), and
      the origin recognition complex 2 protein (ORC2) and was enriched in
      hyperacetylated histones H3 and H4 relative to other regions of the latent
      genome. Cell cycle analysis indicated that the minichromosome maintenance complex
      protein, MCM3, bound TR in late-G(1)/S-arrested cells, which coincided with the
      loss of histone H3 K4 methylation. Micrococcal nuclease studies revealed that TRs
      are embedded in a highly ordered nucleosome array that becomes disorganized in
      late G(1)/S phase. ORC binding to TR was LANA dependent when reconstituted in
      transfected plasmids. DNA affinity purification confirmed that LANA, CBP, BRD2,
      and ORC2 bound TR specifically and identified the histone acetyltransferase HBO1
      (histone acetyltransferase binding to ORC1) as a potential TR binding protein.
      Disruption of ORC2, MCM5, and HBO1 expression by small interfering RNA reduced
      LANA-dependent DNA replication of TR-containing plasmids. These findings are the
      first demonstration that cellular replication and origin licensing factors are
      required for KSHV latent cycle replication. These results also suggest that the
      KSHV latent origin of replication is a unique chromatin environment containing
      histone H3 hyperacetylation within heterochromatic tandem repeats.

PMID- 15507646
TI  - The transmembrane domains of the prM and E proteins of yellow fever virus are
      endoplasmic reticulum localization signals.
AB  - The immature flavivirus particle contains two envelope proteins, prM and E, that
      are associated as a heterodimer. Virion morphogenesis of the flaviviruses occurs
      in association with endoplasmic reticulum (ER) membranes, suggesting that there
      should be accumulation of the virion components in this compartment. This also
      implies that ER localization signals must be present in the flavivirus envelope
      proteins. In this work, we looked for potential subcellular localization signals
      in the yellow fever virus envelope proteins. Confocal immunofluorescence analysis
      of the subcellular localization of the E protein in yellow fever virus-infected
      cells indicated that this protein accumulates in the ER. Similar results were
      obtained with cells expressing only prM and E. Chimeric proteins containing the
      ectodomain of CD4 or CD8 fused to the transmembrane domains of prM or E were
      constructed, and their subcellular localization was studied by confocal
      immunofluorescence and by analyzing the maturation of their associated glycans.
      Although a small fraction was detected in the ER-to-Golgi intermediate and Golgi
      compartments, these chimeric proteins were located mainly in the ER. The C
      termini of prM and E form two antiparallel transmembrane alpha-helices.
      Interestingly, the first transmembrane passage contains enough information for ER
      localization. Taken altogether, these data indicate that, besides their role as
      membrane anchors, the transmembrane domains of yellow fever virus envelope
      proteins are ER retention signals. In addition, our data show that the mechanisms
      of ER retention of the flavivirus and hepacivirus envelope proteins are
      different.

PMID- 15507647
TI  - Enhanced cellular receptor usage by a bioselected variant of coxsackievirus a21.
AB  - Decay-accelerating factor (DAF) functions as cell attachment receptor for a wide
      range of human enteroviruses. The Kuykendall prototype strain of coxsackievirus
      A21 (CVA21) attaches to DAF but requires interactions with intercellular cell
      adhesion molecule 1 (ICAM-1) to infect cells. We show here that a bioselected
      variant of CVA21 (CVA21-DAFv) generated by multiple passages in DAF-expressing,
      ICAM-1-negative rhabdomyosarcoma (RD) cells acquired the capacity to induce rapid
      and complete lysis of ICAM-1-deficient cells while retaining the capacity to bind
      ICAM-1. CVA21-DAFv binding to DAF on RD cells mediated lytic infection and was
      inhibited by either antibody blockade with a specific anti-DAF SCR1 monoclonal
      antibody (MAb) or soluble human DAF. Despite being bioselected in RD cells, CVA21
      DAFv was able to lytically infect an additional ICAM-1-negative cancer cell line
      via DAF interactions alone. The finding that radiolabeled CVA21-DAFv virions are
      less readily eluted from surface-expressed DAF than are parental CVA21 virions
      during a competitive epitope challenge by an anti-DAF SCR1 MAb suggests that
      interactions between CVA21-DAFv and DAF are of higher affinity than those of the
      parental strain. Nucleotide sequence analysis of the capsid-coding region of the
      CVA21-DAFv revealed the presence of two amino acid substitutions in capsid
      protein VP3 (R96H and E101A), possibly conferring the enhanced DAF-binding
      phenotype of CVA21-DAFv. These residues are predicted to be embedded at the
      interface of VP1, VP2, and VP3 and are postulated to enhance the affinity of DAF
      interaction occurring outside the capsid canyon. Taken together, the data clearly
      demonstrate an enhanced DAF-using phenotype and expanded receptor utilization of
      CVA21-DAFv compared to the parental strain, further highlighting that capsid
      interactions with DAF alone facilitate rapid multicycle lytic cell infection.

PMID- 15507648
TI  - Epstein-Barr virus infection in ex vivo tonsil epithelial cell cultures of
      asymptomatic carriers.
AB  - Epstein-Barr virus (EBV) is found frequently in certain epithelial pathologies,
      such as nasopharyngeal carcinoma and oral hairy leukoplakia, indicating that the
      virus can infect epithelial cells in vivo. Recent studies of cell lines imply
      that epithelial cells may also play a role in persistent EBV infection in vivo.
      In this report, we show the establishment and characterization of an ex vivo
      culture model of tonsil epithelial cells, a likely site for EBV infection in
      vivo. Primary epithelial-cell cultures, generated from tonsil explants, contained
      a heterogeneous mixture of cells with an ongoing process of differentiation.
      Keratin expression profiles were consistent with the presence of cells from both
      surface and crypt epithelia. A small subset of cells could be latently infected
      by coculture with EBV-releasing cell lines, but not with cell-free virus. We also
      detected viral-DNA, -mRNA, and -protein expression in cultures from EBV-positive
      tonsil donors prior to in vitro infection. We conclude that these cells were
      either already infected at the time of explantation or soon after through cell-to
      cell contact with B cells replicating EBV in the explant. Taken together, these
      findings suggest that the tonsil epithelium of asymptomatic virus carriers is
      able to sustain EBV infection in vivo. This provides an explanation for the
      presence of EBV in naso- and oropharyngeal pathologies and is consistent with
      epithelial cells playing a role in the egress of EBV during persistent infection.

PMID- 15507649
TI  - Evolutionary dynamics of the glycan shield of the human immunodeficiency virus
      envelope during natural infection and implications for exposure of the 2G12
      epitope.
AB  - Elucidation of the kinetics of exposure of neutralizing epitopes on the envelope
      of human immunodeficiency virus type 1 (HIV-1) during the course of infection may
      provide key information about how HIV escapes the immune system or why its
      envelope is such a poor immunogen to induce broadly efficient neutralizing
      antibodies. We analyzed the kinetics of exposure of the epitopes corresponding to
      the broadly neutralizing human monoclonal antibodies immunoglobulin G1b12
      (IgG1b12), 2G12, and 2F5 at the quasispecies level during infection. We studied
      the antigenicity and sequences of 94 full-length envelope clones present during
      primary infection and at least 4 years later in four HIV-1 clade B-infected
      patients. No or only minor exposure differences were observed for the 2F5 and
      IgG1b12 epitopes between the early and late clones. Conversely, the envelope
      glycoproteins of the HIV-1 quasispecies present during primary infection did not
      expose the 2G12 neutralizing epitope, unlike those present after several years in
      three of the four patients. Sequence analysis revealed major differences at
      potential N-linked glycosylation sites between early and late clones,
      particularly at positions known to be important for 2G12 binding. Our study, in
      natural mutants, confirms that the glycosylation sites N295, N332, and N392 are
      essential for 2G12 binding. This study demonstrates the relationship between the
      evolving "glycan shield " of HIV and the kinetics of exposure of the 2G12 epitope
      during the course of natural infection.

PMID- 15507650
TI  - Human immunodeficiency virus type 1 (HIV-1)-specific CD4+ T cells that
      proliferate in vitro detected in samples from most viremic subjects and inversely
      associated with plasma HIV-1 levels.
AB  - Diminished in vitro proliferation of human immunodeficiency virus type 1 (HIV-1)
      specific CD4+T cells has been associated with HIV-1 viremia and declining CD4+ T
      cell counts during chronic infection. To better understand this phenomenon, we
      examined whether HIV-1 Gag p24 antigen-induced CD4+ T-cell proliferation might
      recover in vitro in a group of subjects with chronic HIV-1 viremia and no history
      of antiretroviral therapy (ART). We found that depletion of CD8+ cells from
      peripheral blood mononuclear cells (PBMC) before antigen stimulation was
      associated with a 6.5-fold increase in the median p24-induced CD4+ T-cell
      proliferative response and a 57% increase in the number of subjects with positive
      responses. These p24-induced CD4+ T-cell proliferative responses from CD8
      depleted PBMC were associated with expansion of the numbers of p24-specific,
      gamma interferon (IFN-gamma)-producing CD4+ T cells. Among the 20 viremic,
      treatment-naive subjects studied, the only 5 subjects lacking proliferation
      competent, p24-specific CD4+ T-cell responses from CD8-depleted PBMC showed
      plasma HIV-1 RNA levels > 100,000 copies/ml. Furthermore, both the magnitude of
      p24-induced CD4+ T-cell proliferative responses from CD8-depleted PBMC and the
      frequency of p24-specific, IFN-gamma-producing CD4+ T cells expanded from CD8
      depleted PBMC were associated inversely with plasma HIV-1 RNA levels. Therefore,
      proliferation-competent, HIV-1-specific CD4+ T cells that might help control HIV
      1 disease may persist during chronic, progressive HIV-1 disease except at very
      high levels of in vivo HIV-1 replication.

PMID- 15507651
TI  - Serotype-specific entry of dengue virus into liver cells: identification of the
      37-kilodalton/67-kilodalton high-affinity laminin receptor as a dengue virus
      serotype 1 receptor.
AB  - Dengue virus, the causative agent of dengue fever, dengue shock syndrome, and
      dengue hemorrhagic fever, infects susceptible cells by initially binding to a
      receptor(s) located on the host cell surface. Evidence to date suggests that
      receptor usage may be cell and serotype specific, and this study sought to
      identify dengue virus serotype 1 binding proteins on the surface of liver cells,
      a known target organ. By using a virus overlay protein binding assay (VOPBA), in
      both nondenaturing and denaturing gel systems, a putative dengue virus serotype 1
      binding protein of approximately 37 kDa expressed on the surface of liver (HepG2)
      cells was identified. Mass spectrometry analysis identified a candidate protein,
      the 37/67-kDa high-affinity laminin receptor. Entry of the dengue virus serotype
      1 was significantly inhibited in a dose-dependent manner by both antibodies
      directed against the 37/67-kDa high-affinity laminin receptor and soluble
      laminin. No inhibition of virus entry was seen with dengue virus serotypes 2, 3,
      or 4, demonstrating that the 37/67-kDa high-affinity laminin receptor is a
      serotype-specific receptor for dengue virus entry into liver cells.

PMID- 15507652
TI  - Identification of TAZ as a binding partner of the polyomavirus T antigens.
AB  - A polyomavirus mutant isolated by the tumor host range selection procedure (19)
      has a three-amino-acid deletion (Delta2-4) in the common N terminus of the T
      antigens. To search for a cellular protein bound by wild-type but not the mutant
      T antigen(s), a yeast two-hybrid screen of a mouse embryo cDNA library was
      carried out with a bait of wild-type small T antigen (sT) fused N terminally to
      the DNA-binding domain of Gal4. TAZ, a transcriptional coactivator with a WW
      domain and PDZ-binding motif (17), was identified as a binding partner. TAZ bound
      in vivo to all three T antigens with different apparent affinities estimated as
      1:7:100 (large T antigen [lT]:middle T antigen [mT]:sT). The Delta2-4 mutant T
      antigens showed no detectable binding. The sT and mT of the host range
      transformation-defective (hr-t) mutant NG59 with an alteration in the common
      sT/mT region (179 D-->NI) and a normal N terminus also failed to bind TAZ, while
      the unaltered lT bound but with reduced affinity compared to that seen in a wild
      type virus infection. The WW domain but not the PDZ-binding motif of TAZ was
      essential for T antigen binding. The Delta2-4 mutant was defective in viral DNA
      replication. Forced overexpression of TAZ blocked wild-type DNA replication in a
      manner dependent on the binding site for the polyomavirus enhancer-binding
      protein 2alpha. Wild-type polyomavirus T antigens effectively block
      transactivation by TAZ. The functional significance of TAZ interactions with
      polyomavirus T antigens is discussed.

PMID- 15507653
TI  - Neuraminidase is important for the initiation of influenza virus infection in
      human airway epithelium.
AB  - Influenza virus neuraminidase (NA) plays an essential role in release and spread
      of progeny virions, following the intracellular viral replication cycle. To test
      whether NA could also facilitate virus entry into cell, we infected cultures of
      human airway epithelium with human and avian influenza viruses in the presence of
      the NA inhibitor oseltamivir carboxylate. Twenty- to 500-fold less cells became
      infected in drug-treated versus nontreated cultures (P < 0.0001) 7 h after virus
      application, indicating that the drug suppressed the initiation of infection.
      These data demonstrate that viral NA plays a role early in infection, and they
      provide further rationale for the prophylactic use of NA inhibitors.

PMID- 15507654
TI  - Structure and polymorphism of the UL6 portal protein of herpes simplex virus type
      1.
AB  - By electron microscopy and image analysis, we find that baculovirus-expressed UL6
      is polymorphic, consisting of rings of 11-, 12-, 13-, and 14-fold symmetry. The
      12-mer is likely to be the oligomer incorporated into procapsids: at a resolution
      of 16 A, it has an axial channel, peripheral flanges, and fits snugly into a
      vacant vertex site. Its architecture resembles those of bacteriophage
      portal/connector proteins.

PMID- 15507655
TI  - Immunization with modified vaccinia virus Ankara-based recombinant vaccine
      against severe acute respiratory syndrome is associated with enhanced hepatitis
      in ferrets.
AB  - Severe acute respiratory syndrome (SARS) caused by a newly identified coronavirus
      (SARS-CoV) is a serious emerging human infectious disease. In this report, we
      immunized ferrets (Mustela putorius furo) with recombinant modified vaccinia
      virus Ankara (rMVA) expressing the SARS-CoV spike (S) protein. Immunized ferrets
      developed a more rapid and vigorous neutralizing antibody response than control
      animals after challenge with SARS-CoV; however, they also exhibited strong
      inflammatory responses in liver tissue. Inflammation in control animals exposed
      to SARS-CoV was relatively mild. Thus, our data suggest that vaccination with
      rMVA expressing SARS-CoV S protein is associated with enhanced hepatitis.

PMID- 15507656
TI  - Novel role for decay-accelerating factor in coxsackievirus A21-mediated cell
      infectivity.
AB  - Decay-accelerating factor (DAF) is involved in the cell membrane attachment of
      many human enteroviruses. Presently, further specific active roles of DAF in
      mediating productive cell infection and in the pathogenesis of natural
      enterovirus infection are poorly understood. In an attempt to more fully
      understand the role of DAF in lytic cell infection we examined the specific
      interactions of the prototype strain of coxsackievirus A21 (CVA21) with surface
      expressed DAF. Investigations into discrete DAF-CVA21 interactions focused on
      viral binding; viral particle elution with respect to the parameters of time,
      temperature, and pH; and subsequent cell infection. Radiolabeled-virus binding
      assays revealed that peak elution of CVA21 from DAF occurred within 15 min of
      initial attachment and that the DAF-eluted virus increased in a linear fashion
      with respect to temperature and pH. CVA21 eluted from endogenous surface
      expressed DAF was highly infectious, in contrast to CVA21 eluted from
      intercellular adhesion molecule 1 (ICAM-1), which retained little to no
      infectivity. Using an adenovirus transduction system, we demonstrate that CVA21
      can remain infectious for up to 24 h after DAF binding and is capable of
      initiating a multicycle lytic infection upon delayed ICAM-1 surface expression.
      Taken together, the data suggest that a major role of DAF in cell infection by
      the prototype strain of CVA21 is to provide membrane concentration of infectious
      virions, effectively increasing viral interactions with endogenous or induced
      ICAM-1.

PMID- 15507657
TI  - The nucleoprotein is required for efficient coronavirus genome replication.
AB  - The construction of a set of transmissible gastroenteritis coronavirus (TGEV)
      derived replicons as bacterial artificial chromosomes is reported. These
      replicons were generated by sequential deletion of nonessential genes for virus
      replication, using a modified TGEV full-length cDNA clone containing unique
      restriction sites between each pair of consecutive genes. Efficient activity of
      TGEV replicons was associated with the presence of the nucleoprotein provided
      either in cis or in trans. TGEV replicons were functional in several cell lines,
      including the human cell line 293T, in which no or very low cytopathic effect was
      observed, and expressed high amounts of heterologous protein.

PMID- 15507658
TI  - Vpr and Vpu are important for efficient human immunodeficiency virus type 1
      replication and CD4+ T-cell depletion in human lymphoid tissue ex vivo.
AB  - The relevance of the accessory vpr, vpu, and nef genes for human immunodeficiency
      virus type 1 (HIV-1) replication in human lymphoid tissue (HLT), the major site
      of viral replication in vivo, is largely unknown. Here, we show that an
      individual deletion of nef, vpr, or vpu significantly decreases HIV-1 replication
      and prevents CD4+ T-cell depletion in ex vivo HLT. However, only combined defects
      in all three accessory genes entirely disrupt the replicative capacity of HIV-1.
      Our results demonstrate that nef, vpr, and vpu are all essential for efficient
      viral spread in HLT, suggesting an important role in AIDS pathogenesis.

PMID- 15507659
TI  - EBNA2 is required for protection of latently Epstein-Barr virus-infected B cells
      against specific apoptotic stimuli.
AB  - In addition to functioning as a transcriptional transactivator, Epstein-Barr
      virus EBNA2 interacts with Nur77 to protect against Nur77-mediated apoptosis.
      Estrogen-regulated EBNA2 in EREB2-5 cells was replaced by either EBNA2 or EBNA2
      with a deletion of conserved region 4 (EBNA2DeltaCR4). Both EBNA2-converted and
      EBNA2DeltaCR4-converted EREB2-5 cells grew in the absence of estrogen and
      expressed LMP1. Treatment with tumor necrosis factor alpha did not induce
      apoptosis of EBNA2- or EBNA2DeltaCR4-expressing cells, but EBNA2DeltaCR4 cells
      were susceptible to etoposide and 5-fluorouracil, Nur77-mediated inducers of
      apoptosis. Thus, EBNA2 protects B cells against specific apoptotic agents against
      which LMP1 is not effective.

PMID- 15507660
TI  - Characterization of a novel close-to-root papillomavirus from a Florida manatee
      by using multiply primed rolling-circle amplification: Trichechus manatus
      latirostris papillomavirus type 1.
AB  - By using an isothermal multiply primed rolling-circle amplification protocol, the
      complete genomic DNA of a novel papillomavirus was amplified from a skin lesion
      biopsy of a Florida manatee (Trichechus manatus latirostris), one of the most
      endangered marine mammals in United States coastal waters. The nucleotide
      sequence, genome organization, and phylogenetic position of the Trichechus
      manatus latirostris papillomavirus type 1 (TmPV-1) were determined. TmPV-1 is the
      first virus isolated from the order of Sirenia. A phylogenetic analysis shows
      that TmPV-1 is only distantly related to other papillomavirus sequences, and it
      appears in our phylogenetic tree as a novel close-to-root papillomavirus genus.

PMID- 15507661
TI  - Host range factor 1 from Lymantria dispar Nucleopolyhedrovirus (NPV) is an
      essential viral factor required for productive infection of NPVs in IPLB-Ld652Y
      cells derived from L. dispar.
AB  - Host range factor 1 (HRF-1) of Lymantria dispar multinucleocapsid
      nucleopolyhedrovirus promotes Autographa californica MNPV replication in
      nonpermissive Ld652Y cells derived from L. dispar. Here we demonstrate that
      restricted Hyphantria cunea NPV replication in Ld652Y cells was not due to
      apoptosis but was likely due to global protein synthesis arrest that could be
      restored by HRF-1. Our data also showed that HRF-1 promoted the production of
      progeny virions for two other baculoviruses, Bombyx mori NPV and Spodoptera
      exigua MNPV, whose replication in Ld652Y cells is limited to replication of viral
      DNA without successful production of infectious progeny virions. Thus, HRF-1 is
      an essential viral factor required for productive infection of NPVs in Ld652Y
      cells.

PMID- 15507662
TI  - Seminal fluid enhances replication of human T-cell leukemia virus type 1:
      implications for sexual transmission.
AB  - Seminal fluid enhanced human T-cell leukemia virus type 1 (HTLV-1) infection by
      transactivating the HTLV-1 long terminal repeat promoter, which is chromosomally
      integrated in a cell-type-dependent manner. Our data may indicate a potential
      role for seminal fluid in the sexual transmission of HTLV-1 and imply complex
      features of regulation of HTLV-1 expression.

PMID- 15507663
TI  - The phylogeography of orangutan foamy viruses supports the theory of ancient
      repopulation of Sumatra.
AB  - Phylogenetic analysis of foamy virus sequences obtained from Bornean and Sumatran
      orangutans showed a distinct clustering pattern. One subcluster was represented
      by both Bornean and Sumatran orangutan simian foamy viruses (SFV). Combined
      analysis of host mitochondrial DNA and SFV phylogeny provided evidence for the
      hypothesis of the repopulation of Sumatra by orangutans from Borneo.

PMID- 15507664
TI  - Study of sequence variation of dengue type 3 virus in naturally infected
      mosquitoes and human hosts: implications for transmission and evolution.
AB  - Dengue virus is an arbovirus that replicates alternately in the mosquito vector
      and human host. We investigated sequences of dengue type 3 virus in naturally
      infected Aedes aegypti mosquitoes and in eight patients from the same outbreak
      and reported that the extent of sequence variation seen with the mosquitoes was
      generally lower than that seen with the patients (mean diversity, 0.21 versus
      0.38% and 0.09 versus 0.23% for the envelope [E] and capsid [C] genes,
      respectively). This was further verified with five experimentally infected
      mosquitoes (mean diversity, 0.09 and 0.10% for the E and C genes, respectively).
      Examination of the quasispecies structures of the E sequences of the mosquitoes
      and of the patients revealed that the sequences of the major variants were the
      same, suggesting that the major variant was transmitted. These findings support
      our hypothesis that mosquitoes contribute to the evolutionary conservation of
      dengue virus by maintaining a more homogenous viral population and a dominant
      variant during transmission.

PMID- 15507665
TI  - Hereditary non-syndromic sensorineural hearing loss: transforming silence to
      sound.
AB  - Tremendous progress has been made in our understanding of the molecular basis of
      hearing and hearing loss. Through recent advances, we have begun to understand
      the fascinating biology of the auditory system and unveiled new molecular
      mechanisms of hearing impairment. Changes in the diagnostic impact of genetic
      testing have occurred, as well as exciting developments in therapeutic options.
      Molecular diagnosis, which is already a reality for several hearing-associated
      genes, will doubtlessly continue to increase in the near future, both in terms of
      the number of mutations tested and the spectrum of genes. Genetic analysis for
      hearing loss is mostly used for diagnosis and treatment, and relatively rarely
      for reproductive decisions, in contrast to other inherited disorders. Inherited
      hearing loss, however, is characterized by impressive genetic heterogeneity. An
      abundance of genes carry a large number of mutations, but specific mutations in a
      single gene may lead to syndromic or non-syndromic hearing loss. Some mutations
      predominate in individual ethnic groups. For clinical and laboratory
      diagnosticians, it is challenging to keep abreast of the unfolding discoveries.
      This review aims to provide the framework pertinent to diagnosticians and a
      practical approach to mutation analysis in the hearing impaired.

PMID- 15507666
TI  - Triplet repeat primed PCR (TP PCR) in molecular diagnostic testing for Friedreich
      ataxia.
AB  - Friedreich ataxia (FRDA), an autosomal recessive neurodegenerative disease, is
      associated with an unstable expansion of a GAA trinucleotide repeat in the first
      intron of the frataxin gene on chromosome 9q13. Unequivocal molecular
      characterization of the FRDA triplet expansion requires the use of different PCR
      protocols to amplify normal and mutated alleles combined with Southern blotting
      analysis to accurately size the expansion. Nevertheless, expansion detection by
      PCR may be somewhat problematic in heterozygous individuals. The purpose of this
      study was to evaluate triplet repeat primed PCR (TP PCR) as a screening method
      for FRDA diagnosis in the diagnostic laboratory. Fifty-four cases referred either
      to confirm the diagnosis of FRDA or to detect carrier status were re-evaluated by
      the TP PCR method. The TP PCR assay correctly identified the FRDA status in all
      54 individuals tested including homozygous expansions (9 individuals),
      heterozygous expansions (20 individuals), and non-carriers (25 individuals).
      Results showed 100% concordance with those obtained by Southern blot analysis. TP
      PCR allowed us to identify the expanded alleles or to demonstrate their absence
      in DNA samples where conventional PCR procedures failed to give a reliable
      result. TP PCR represents an additional valuable tool for mutation detection in
      FRDA patients and carriers, but also can be used as screening test in a
      diagnostic laboratory.

PMID- 15507667
TI  - RT-PCR analysis of RNA extracted from Bouin-fixed and paraffin-embedded lymphoid
      tissues.
AB  - In the present study, we have investigated whether RNA can be efficiently
      isolated from Bouin-fixed or formalin-fixed, paraffin-embedded lymphoid tissue
      specimens. To this aim, we applied a new and simple method that includes the
      combination of proteinase K digestion and column purification. By this method, we
      demonstrated that the amplification of long fragments could be accomplished after
      a pre-heating step before cDNA synthesis associated with the use of enzymes that
      work at high temperature. By means of PCR using different primers for two
      examined genes (glyceraldehyde-3-phosphate dehydrogenase [GAPDH]- and CD40), we
      amplified segments of cDNA obtained by reverse transcription of the isolated RNA
      extracted from Bouin-fixed or formalin-fixed paraffin-embedded tissues. Amplified
      fragments of the expected sizes were obtained for both genes tested indicating
      that this method is suitable for the isolation of high-quality RNA. To explore
      the possibility for giving accurate real time quantitative RT-PCR results, cDNA
      obtained from matched frozen, Bouin-fixed and formalin-fixed neoplastic samples
      (two diffuse large cell lymphomas, one plasmacytoma) was tested for the following
      target genes: CD40, Aquaporin-3, BLIMP1, IRF4, Syndecan-1. Delta threshold cycle
      (DeltaC(T)) values for Bouin-fixed and formalin-fixed paraffin-embedded tissues
      and their correlation with those for frozen samples showed an extremely high
      correlation (r > 0.90) for all of the tested genes. These results show that the
      method of RNA extraction we propose is suitable for giving accurate real time
      quantitative RT-PCR results.

PMID- 15507668
TI  - Constitutive expression of the AP-1 transcription factors c-jun, junD, junB, and
      c-fos and the marginal zone B-cell transcription factor Notch2 in splenic
      marginal zone lymphoma.
AB  - Splenic marginal zone lymphoma (SMZL) is a lymphoma type of putative marginal
      zone B-cell origin. No specific genetic alterations have yet been demonstrated in
      SMZL. Clinically, SMZL is a low-grade B-cell non-Hodgkin lymphoma. However, the
      presence of p53 mutation, 7q22-7q32 deletion or the absence of somatic
      hypermutations of immunoglobulin genes has been correlated with a worse
      prognosis. In this study, we analyzed genome-wide gene expression of 24 cases of
      SMZL using the microarray technique. The AP-1 transcription factors c-jun, junD,
      junB, and c-fos as well as Notch2 were found to be specifically up-regulated.
      These data were confirmed by real-time PCR and immunohistochemical staining of
      tissue sections. The absence of concordant high expression of the MAP kinases,
      the signaling cascade leading to AP-1 up-regulation, suggests autoregulation of
      the AP-1 transcription factors and an important role in SMZL oncogenesis. High
      expression of Notch2, a transcription factor that induces marginal zone B-cell
      differentiation, is highly suggestive for a marginal zone B-cell origin of SMZL.
      In addition, SMZL with the 7q deletion showed high expression of TGF-beta1 and
      low expression of the DNA helicase XPB, a crucial part of the nucleotide excision
      repair complex, possibly explaining the more aggressive clinical course of those
      cases.

PMID- 15507669
TI  - Challenges and pitfalls in HNPCC screening by microsatellite analysis and
      immunohistochemistry.
AB  - Hereditary non-polyposis colorectal cancer (HNPCC) accounts for approximately 2
      to 4% of the total colorectal cancer burden. For economic reasons a diagnostic
      "stepladder" is recommended. After evaluation of the family history, diagnostic
      microsatellite instability (MSI) analysis has found its place as a valuable
      screening tool for HNPCC. Immunohistochemical analysis can help to pinpoint the
      affected gene. The detection of a mutation in one of the responsible mismatch
      repair gene confirmed the diagnosis HNPCC. Here we demonstrate our experience of
      some important pitfalls that will be discussed in this study. In MSI testing, one
      potential source for false-negative results is intralesional heterogeneity. We
      demonstrate examples of a flat adenoma and a carcinoma, which required laser
      microdissection to correctly determine the microsatellite status. In these
      lesions manual microdissection, the most frequently applied method, was not
      sufficient. However, the number of cells obtained by using laser microdisssection
      can fall below a necessary minimum, which can also cause false-negative results
      of MSI analysis, as shown here in a mucinous carcinoma. In addition, evaluation
      of immunohistochemically stained tissue slides requires experience to avoid false
      positive or false-negative interpretation. A case with two synchronous colorectal
      cancers revealed loss of MSH2 expression in one carcinoma, whereas the second
      carcinoma stained positively leading to a false-negative interpretation. In some
      cases, false-positive results can be obtained, if a perinuclear-staining pattern
      is interpreted as positive. In summary, there are several potential pitfalls in
      the molecular screening for HNPCC. Therefore the importance of correct
      interpretation of clinical data, immunohistochemistry, and microsatellite
      analysis in combination, performed by a pathologist with experience in molecular
      genetics is essential. In addition, laser microdissection of tumor areas that
      have been chosen by a pathologist is highly recommended in cases that cannot be
      resolved with manual microdissection.

PMID- 15507670
TI  - Intratumoral patterns of clonal evolution in meningiomas as defined by multicolor
      interphase fluorescence in situ hybridization (FISH): is there a relationship
      between histopathologically benign and atypical/anaplastic lesions?
AB  - Meningiomas are cytogenetically heterogeneous tumors in which chromosome gains
      and losses frequently occur. Based on the intertumoral cytogenetic heterogeneity
      of meningiomas, hypothetical models of clonal evolution have been proposed in
      these tumors which have never been confirmed at the intratumoral cell level. The
      aim of this study was to establish the intratumoral patterns of clonal evolution
      associated with chromosomal instability in individual patients as a way to
      establish tumor progression pathways in meningiomas and their relationship with
      tumor histopathology and behavior. A total of 125 meningioma patients were
      analyzed at diagnosis. In all cases, multicolor interphase fluorescence in situ
      hybridization (iFISH) studies were performed on fresh tumor samples for the
      detection of quantitative abnormalities for 11 different chromosomes. In
      addition, overall tumor cell DNA content was measured in parallel by flow
      cytometry. iFISH studies were also performed in parallel on tissue sections in a
      subset of 30 patients. FISH studies showed that 56 (45%) of the 125 cases
      analyzed had a single tumor cell clone, all these cases corresponding to
      histologically benign grade I tumors. In the remaining cases (55%) more than one
      tumor cell clone was identified: two in 45 cases (36%), three in 19 (15%), and
      four or more clones in five cases (4%). Overall, flow cytometric analysis of cell
      DNA contents showed the presence of DNA aneuploidy in 44 of these cases (35%),
      30% corresponding to DNA hyperdiploid and 5% to hypodiploid cases; from the DNA
      aneuploid cases, 35 (28%) showed two clones and 9 (7%) had three or more clones.
      A high degree of correlation (r >/= 0.89; P < 0.001) was found between FISH and
      flow cytometry as regards the overall quantitative DNA changes detected with both
      techniques, the former being more sensitive. Among the cases with chromosome
      abnormalities, the earliest tumor cell clone observed was frequently
      characterized by the loss of one or more chromosomes (64% of all meningiomas);
      loss of either a single chromosome 22 or, less frequently, of a sex chromosome (X
      or Y) and del (1p) was commonly found as the single initial cytogenetic
      aberration (30%, 5%, and 5% of the cases, respectively). Interestingly, an
      isolated loss of chromosome 22 was only found as the initial abnormality in one
      out of 14 atypical/anaplastic meningiomas, while the same cytogenetic pattern was
      present in the ancestral tumor cell clone of 32% of the benign tumors.
      Cytogenetic patterns based on chromosome gains were found in the ancestral tumor
      cell clone in 4% of the patients, 2% corresponding to tetraploid tumors. Overall,
      cytogenetic evolution of the earliest tumor cell clones was frequently associated
      with tetraploidization (31%). Our results show that meningiomas are genetically
      heterogeneous tumors that display different patterns of numerical chromosome
      changes, with the presence of more than one tumor cell clone detected in almost
      half of the cases including all atypical/anaplastic cases. Interestingly, the
      pathways of intratumoral clonal evolution observed in the benign tumors were
      different from those observed in atypical/anaplastic meningiomas, suggesting that
      the latter tumors might not always represent a more advanced stage of
      histologically benign meningiomas.

PMID- 15507671
TI  - Promoter hypermethylation of multiple genes in hydatidiform mole and
      choriocarcinoma.
AB  - The methylation status of genes in hydatidiform mole and choriocarcinoma and its
      significance is relatively unexplored. We investigated the methylation status of
      the promoter regions of six genes, p16, HIC-1, TIMP3, GSTP1, death-associated
      protein kinase (DAPK), and E-cadherin in 54 hydatidiform moles, five
      choriocarcinomas, and 10 first trimester placenta by methylation-specific
      polymerase chain reaction (PCR). Immunohistochemical expression of p16, TIMP3,
      and E-cadherin, and quantitative real-time RT-PCR of p16 was also performed.
      Among the six genes examined, the promoter region of four genes (E-cadherin, HIC
      1, p16, TIMP3) in choriocarcinoma and three genes (E-cadherin, HIC-1, p16) in
      hydatidiform mole exhibited aberrant methylation whereas none was hypermethylated
      in normal placenta. There was a significant correlation between methylation and
      reduced expression of p16, E-cadherin, and TIMP3 (P < 0.001). Fifteen of the 54
      patients with hydatidiform mole developed gestational trophoblastic neoplasia
      requiring chemotherapy. Promoter hypermethylation of p16 alone, or combined with
      E-cadherin, was significantly correlated to such development (P = 0.001, 0.0005,
      respectively). Hypermethylation of multiple genes, especially p16, might be
      related to the subsequent development of gestational trophoblastic neoplasia.

PMID- 15507672
TI  - Demonstration that mast cells, T cells, and B cells bearing the activating kit
      mutation D816V occur in clusters within the marrow of patients with mastocytosis.
AB  - Mastocytosis is characterized by focal heterotypic clusters of mast cells and
      lymphocytes in the bone marrow and by a somatically acquired activating Kit
      mutation, D816V. The relationship of the occurrence of this mutation to the
      heterotypic clusters of mast cells and lymphocytes in bone marrow is unknown. We
      hypothesized that these two unique features of mastocytosis were related. To
      explore this hypothesis, laser capture microdissected mast cells, B cells, and T
      cells, from both lesional and non-lesional areas of bone marrow biopsy tissues
      from patients with mastocytosis, were examined for the D816V mutation in their
      DNA, using HinfI restriction digestion of nested PCR products amplified from
      extracts of dissected cells. The D816V mutation was detected in mast cells, B
      cells, and T cells from lesional but not non-lesional areas of bone marrow
      tissues. B cells obtained from lesional areas of tissue were also assessed for
      clonality and were found to at least represent an oligoclonal population. Thus,
      mast cells and lymphocytes within focal aggregates in the bone marrow of those
      with mastocytosis are more frequently positive for the codon 816 activating
      mutation. Further, the B cell population is oligoclonal, suggesting that clonal
      proliferation is unlikely to be the basis of clustering.

PMID- 15507673
TI  - Characterization of the different BCR-ABL transcripts with a single multiplex RT
      PCR.
AB  - The diagnosis of chronic myeloid leukemia is based on detection of the
      Philadelphia (Ph) chromosome or the BCR-ABL gene. The junction present in the
      transcript may vary according to the reciprocal translocation t(9;22)(q34;11).
      Identification of the transcript (p190, p210 or p230) does not reveal the type of
      junction but this information is very important for classification of patients in
      clinical trials. Most identification kits do not explore p230 transcripts and are
      unable to determine exotic breakpoints. We have developed a clinical molecular
      diagnosis assay, able to identify all of the BCR-ABL transcripts and, by single
      assay, to characterize all of the possible transcript junctions. This technique
      is based on RT-PCR and PCR-capillary electrophoresis. For each patient sample, we
      performed RT-PCR with three different BCR primers each coupled to a specific
      different fluorochrome and a unique reverse ABL primer. Depending on the
      transcript, only one BCR primer was used for each RT-PCR. After capillary
      electrophoresis and fluorescence determination, we were able to identify both the
      transcript and its junction at the same time.

PMID- 15507674
TI  - Microsphere bead arrays and sequence validation of 5/7/9T genotypes for multiplex
      screening of cystic fibrosis polymorphisms.
AB  - The development of simple and rapid methods for the detection of the common
      genetic mutations associated with cystic fibrosis (CF) requires access to
      positive-control samples including the 5/7/9T variants of intron 8. We used PCR
      and a simple multiplex bead-array assay to identify 5/7/9T control samples from
      29 commercially available DNA samples. Unpurified PCR products were directly
      hybridized to color-coded beads containing allele-specific capture probes for
      5/7/9T detection. The performance of the assay was investigated using reverse
      complement oligonucleotides, individual PCR products, and multiplex PCR products
      for 5/7/9T detection within a complex CFTR screening assay. Samples were
      genotyped by grouping the relative signal intensities from each capture probe. Of
      29 commercially available DNA samples analyzed, 2 5T/7T, 2 5T/9T, 9 7T/9T, 11
      7T/7T, and 5 9T/9T genotypes were identified. The genotype within each sample
      group was confirmed by DNA sequencing. The assay was compatible with the analysis
      of 10 to 1000 ng of genomic DNA isolated from whole blood and allowed for the
      separate identification of primary CFTR mutations from reflex variants. The
      correct identification of positive controls demonstrated the utility of a simple
      bead-array assay and provided accessible samples for assay optimization and for
      routine quality control in the clinical laboratory.

PMID- 15507675
TI  - Measurement of relative copy number of CDKN2A/ARF and CDKN2B in bladder cancer by
      real-time quantitative PCR and multiplex ligation-dependent probe amplification.
AB  - Many tumors have large homozygous deletions of the CDKN2A locus (encoding
      p14(ARF) and p16) and of CDKN2B (p15). Our aim was to determine which gene is the
      major target in bladder cancer. We used quantitative real-time PCR (RTQ-PCR) to
      determine copy number of p15, of p14(ARF) exon 1beta, and p16 exon 2 in 22 tumor
      cell lines and 83 bladder tumors, some of which had been assessed previously by
      duplex PCR. Titration experiments showed that homozygous deletion could be
      detected in the presence of up to 30% normal DNA. Results for cell lines were
      compatible with previous cytogenetic analyses. Ten cell lines and 32 tumors
      (38.5%) had homozygous deletion of at least one target. Thirteen tumors (15.7%)
      had deletion of all three targets. Two tumors had deletion of p14(ARF) exon 1beta
      alone and four of p16 exon 2 alone. RTQ-PCR detected more homozygous deletions
      than duplex PCR. Finally we used a multiplex ligation-dependent probe
      amplification kit to provide independent confirmation of results. We conclude
      that with appropriate controls RTQ-PCR is a sensitive and robust method to detect
      copy number changes in tumors even in the presence of contaminating normal cell
      DNA.

PMID- 15507676
TI  - KIT gene deletions at the intron 10-exon 11 boundary in GI stromal tumors.
AB  - Most gastrointestinal stromal tumors (GISTs) harbor oncogenic mutations in the
      KIT gene, and the majority of these mutations affect the juxtamembrane domain of
      the kinase encoded by exon 11. Screening GISTs for KIT gene mutations is
      important for translational research studies and for providing prognostic
      information on the likelihood of tumor response to treatment with the kinase
      inhibitor imatinib mesylate (Gleevec). In a series of GISTs analyzed in our
      laboratory by a combination of denaturing HPLC and direct DNA sequencing, we
      identified 19 cases with KIT exon 11 deletions that included from 1 to 14 bp of
      intron 10 sequence and resulted in loss of the normal splice acceptor site at the
      beginning of exon 11. Predicted use of the next potential splice-acceptor site
      was confirmed by cDNA sequencing in 4 cases. Thus, the resulting mutant isoform,
      deletion KPMYEVQWK 550-558, was the same in all 19 cases. Only two other examples
      of deletions across the intron 10-exon 11 boundary have been reported, yet among
      722 GISTs analyzed in our laboratories these deletions were not uncommon,
      accounting for 3.9% of exon 11 mutations and 2.6% of all tumors. Loss of KIT
      intron 10 sequences may be under-recognized if the forward primer is too close to
      exon 11, or if cases are examined exclusively at the cDNA level. Laboratories
      that offer clinical screening for KIT mutations in GI stromal tumors should be
      aware of this class of mutations.

PMID- 15507677
TI  - Comparison of snap freezing versus ethanol fixation for gene expression profiling
      of tissue specimens.
AB  - Frozen tissue specimens are the gold standard for molecular analysis. However,
      snap freezing presents several challenges regarding collection and storage of
      tissue, and preservation of histological detail. We evaluate an alternative
      preservation method, ethanol fixation followed by paraffin embedding, by
      analyzing expression profiles of microdissected cells on Affymetrix
      oligonucleotide arrays of three matched benign prostatic hyperplasia (BPH) and
      tumor samples processed with each preservation method. Frozen samples generated
      an average present call of 26% of the probe sets, compared to 4.5% in ethanol
      paraffin samples. Eighty-eight percent of the probe sets called present in the
      ethanol-paraffin samples were also present in the frozen specimens. Comparing
      ethanol-paraffin BPH to tumor, 52 probe sets showed a twofold differential
      expression or higher in at least two cases, 23 of which were also differentially
      expressed in at least one frozen case. Despite a significant drop in the number
      of transcripts detectable, the data suggests that the obtainable information in
      ethanol-fixed samples may be useful for molecular profiling where frozen tissue
      is not available. However, ethanol fixation and paraffin embedding of tissue
      specimens is not optimal for high-throughput mRNA expression analysis. Improved
      methods for transcript profiling of archival samples, and/or tissue processing
      are still required.

PMID- 15507678
TI  - Epstein-Barr virus quantitation by real-time PCR targeting multiple gene
      segments: a novel approach to screen for the virus in paraffin-embedded tissue
      and plasma.
AB  - Epstein-Barr Virus (EBV) infects nearly all humans and then persists for the life
      of the host. In some people who later develop cancer, EBV DNA is present within
      malignant cells and circulates at elevated levels in the plasma. In the current
      study, we validated five novel quantitative polymerase chain reaction (Q-PCR)
      assays targeting disparate but highly conserved segments of the EBV genome
      (BamH1W, EBNA1, LMP1, LMP2, and BZLF1). Each assay was sensitive to as few as 50
      copies of EBV DNA per reaction and was linear across at least four orders of
      magnitude. When applied to paraffin-embedded tissues in concert with EBV-encoded
      RNA (EBER) in situ hybridization, the BamH1W and EBNA1 assays were the most
      informative, while use of the entire battery of EBV PCR assays may help identify
      genomic polymorphisms or deletions. Higher viral loads were found in the 17 EBER
      positive compared with the 13 EBER-negative tumors (means 84,978 versus 22 copies
      of EBV per 100,000 cells, respectively). The five Q-PCR assays were also
      informative in plasma samples where EBV was measurable in all nine patients with
      lymphoma or infectious mononucleosis, whereas EBV was undetectable in all nine
      healthy controls. The findings suggest that Q-PCR is an effective method of
      distinguishing disease-associated virus from incidental virus in paraffin
      embedded tissue and in plasma samples.

PMID- 15507679
TI  - Enhanced retrieval of DNA from human fecal samples results in improved
      performance of colorectal cancer screening test.
AB  - Colorectal cancer accounts for more than 10% of all cancer deaths but is curable,
      if detected early. We reported previously on a stool-based screening test in
      which DNA from stool samples is subjected to genome analysis; sensitivity of the
      test has been limited in part by inefficiency of retrieving DNA from stool. Our
      aim was to test the impact of a new purification method that would increase the
      yield of human DNA from stool. DNA from 86 cancer and 100 non-cancer subjects
      (diagnosed by colonoscopy) were purified from stool with a new method for DNA
      recovery based on sequence-specific capture with acrylamide gel immobilized
      capture probes as well as with a previously developed magnetic bead-capture
      procedure. The new purification method gives an average 5.4-fold increase in the
      quantity of human DNA that can routinely be retrieved from fecal samples. The
      increased recovery of DNA corresponds with an increase in assay sensitivity from
      53% (CI: 42 to 64%) to 70% (CI: 59 to 79%); P = 0.0005 (by McNemar's test), with
      no change in specificity. The newly developed sample preparation method mitigates
      a major problem in detecting rare cancer-associated genetic changes in
      heterogeneous clinical samples such as stool.

PMID- 15507680
TI  - Quantitative PCR detection of t(14;18) bcl-2/JH fusion sequences in follicular
      lymphoma patients: comparison of peripheral blood and bone marrow aspirate
      samples.
AB  - In patients with follicular lymphoma (FL), it is unresolved whether peripheral
      blood (PB) can replace bone marrow (BM) aspirate samples for detection of bcl
      2/JH fusion sequences that result from the t(14;18)(q32;q21). We compare here the
      results of quantitative polymerase chain reaction (q-PCR) analysis for bcl-2/JH
      involving the major breakpoint cluster region (mbr) on paired PB and BM aspirate
      samples from 60 consecutive FL patients. There was a significant correlation
      between the level of bcl-2/JH fusion sequence obtained from PB and BM aspirate
      samples (r = 0.886), with 82% of samples showing less than one log of difference.
      Patients who had histological evidence of FL involving concurrent BM biopsy
      specimens had moderate to high levels of bcl-2/JH in both PB and BM aspirate
      samples, allowing unequivocal determination of translocation status (median bcl
      2/JH to cyclophilin level was 8.014%). In contrast, patients with no detectable
      FL in their BM biopsy specimens often showed low levels of bcl-2/JH in both PB
      and BM aspirate samples (bcl-2/JH to cyclophilin median level = 0.006%), in a
      range similar to background levels that could be detected in patients without FL
      (n = 15, median bcl-2 mbr/JH to cyclophilin level = 0.002%). We conclude that PB
      can be used in place of BM aspirate samples to test for the presence of bcl-2
      mbr/JH fusion sequence in FL patients and that either PB or BM aspirate testing
      yields a rough approximation of the degree of BM involvement by FL. However, in
      patients with minimal levels of bcl-2/JH in PB or BM aspirate samples,
      confirmation of this result by testing the primary tumor is recommended to
      confirm the presence of an identical bcl-2/JH fusion sequence and exclude false
      positive results.

PMID- 15507681
TI  - A rare mutation in the primer binding region of the amelogenin gene can interfere
      with gender identification.
AB  - PCR amplification of part of the X-Y homologous amelogenin gene with a single
      primer pair has been used as a sex identification test because it generates
      different length products from the X and Y chromosomes. Using a commercially
      available kit that contains amelogenin primers, we report a single phenotypically
      normal Caucasian male out of 327 males tested to date that failed to show an X
      chromosome-specific PCR product. Using alternative amelogenin primers external to
      but encompassing the initial amplicon, an X chromosome-specific product was seen.
      Sequence analysis of this X-specific PCR product revealed a C to G mutation at
      the most 3' base of the initial reverse amelogenin PCR primer. An alternative
      reverse PCR primer with this most 3' base deleted showed X- and Y-specific
      products from the case study male. Rare mutations that result in a failure to
      amplify sex chromosome-specific products can result in incorrect gender
      identification.

PMID- 15507682
TI  - A rapid and efficient method to generate multiple gene disruptions in
      Dictyostelium discoideum using a single selectable marker and the Cre-loxP
      system.
AB  - Dictyostelium discoideum has proven an exceptionally powerful system for studying
      numerous aspects of cellular and developmental functions. The relatively small (
      approximately 34 Mb) chromosomal genome of Dictyostelium and high efficiency of
      targeted gene disruption have enabled researchers to characterize many specific
      gene functions. However, the number of selectable markers in Dictyostelium is
      restricted, as is the ability to perform effective genetic crosses between
      strains. Thus, it has been difficult to create multiple mutations within an
      individual cell to study epistatic relationships among genes or potential
      redundancies between various pathways. We now describe a robust system for the
      production of multiple gene mutations in Dictyostelium by recycling a single
      selectable marker, Blasticidin S resistance, using the Cre-loxP system. We
      confirm the effectiveness of the system by generating a single cell carrying four
      separate gene disruptions. Furthermore, the cells remain sensitive to
      transformation for additional targeted or random mutagenesis requiring
      Blasticidin selection and for functional expression studies of mutated or tagged
      proteins using other selectable markers.

PMID- 15507683
TI  - Reversibly switchable DNA nanocompartment on surfaces.
AB  - Biological macromolecules have been used to fabricate many nanostructures,
      biodevices and biomimetics because of their physical and chemical properties. But
      dynamic nanostructure and biomachinery that depend on collective behavior of
      biomolecules have not been demonstrated. Here, we report the design of DNA
      nanocompartments on surfaces that exhibit reversible changes in molecular
      mechanical properties. Such molecular nanocompartments are used to encage
      molecules, switched by the collective effect of Watson-Crick base-pairing
      interactions. This effect is used to perform molecular recognition. Furthermore,
      we found that 'fuel' strands with single-base variation cannot afford an
      efficient closing of nanocompartments, which allows highly sensitive label-free
      DNA array detection. Our results suggest that DNA nanocompartments can be used as
      building blocks for complex biomaterials because its core functions are
      independent of substrates and mediators.

PMID- 15507684
TI  - One-step random mutagenesis by error-prone rolling circle amplification.
AB  - In vitro random mutagenesis is a powerful tool for altering properties of
      enzymes. We describe here a novel random mutagenesis method using rolling circle
      amplification, named error-prone RCA. This method consists of only one DNA
      amplification step followed by transformation of the host strain, without
      treatment with any restriction enzymes or DNA ligases, and results in a randomly
      mutated plasmid library with 3-4 mutations per kilobase. Specific primers or
      special equipment, such as a thermal-cycler, are not required. This method
      permits rapid preparation of randomly mutated plasmid libraries, enabling random
      mutagenesis to become a more commonly used technique.

PMID- 15507685
TI  - Plasmodium interspersed repeats: the major multigene superfamily of malaria
      parasites.
AB  - Functionally related homologues of known genes can be difficult to identify in
      divergent species. In this paper, we show how multi-character analysis can be
      used to elucidate the relationships among divergent members of gene
      superfamilies. We used probabilistic modelling in conjunction with protein
      structural predictions and gene-structure analyses on a whole-genome scale to
      find gene homologies that are missed by conventional similarity-search strategies
      and identified a variant gene superfamily in six species of malaria (Plasmodium
      interspersed repeats, pir). The superfamily includes rif in P.falciparum, vir in
      P.vivax, a novel family kir in P.knowlesi and the cir/bir/yir family in three
      rodent malarias. Our data indicate that this is the major multi-gene family in
      malaria parasites. Protein localization of products from pir members to the
      infected erythrocyte membrane in the rodent malaria parasite P.chabaudi,
      demonstrates phenotypic similarity to the products of pir in other malaria
      species. The results give critical insight into the evolutionary adaptation of
      malaria parasites to their host and provide important data for comparative
      immunology between malaria parasites obtained from laboratory models and their
      human counterparts.

PMID- 15507686
TI  - Guanosine tetra- and pentaphosphate synthase activity in chloroplasts of a higher
      plant: association with 70S ribosomes and inhibition by tetracycline.
AB  - Chloroplasts possess bacterial-type systems for transcription and translation. On
      the basis of the identification of a Chlamydomonas reinhardtii gene encoding a
      RelA-SpoT homolog (RSH) that catalyzes the synthesis of guanosine tetra- or
      pentaphosphate [(p)ppGpp], we have previously suggested the operation of
      stringent control in the chloroplast genetic system. Although RSH genes have also
      been identified in several higher plants, the activities of the encoded enzymes
      and their mode of action in chloroplasts have remained uncharacterized. We have
      now characterized the intrinsic (p)ppGpp synthase activity of chloroplast
      extracts prepared from pea (Pisum sativum). Fractionation by ultracentrifugation
      suggested that the (p)ppGpp synthase activity of a translationally active
      chloroplast stromal extract was associated with 70S ribosomes. Furthermore, this
      enzymatic activity was inhibited by tetracycline, as was the peptide elongation
      activity of the extract. Structural comparisons between rRNA molecules of
      Escherichia coli and pea chloroplasts revealed the conservation of putative
      tetracycline-binding sites. These observations demonstrate the presence of a
      ribosome-associated (p)ppGpp synthase activity in the chloroplasts of a higher
      plant, further implicating (p)ppGpp in a genetic system of chloroplasts similar
      to that operative in bacteria.

PMID- 15507687
TI  - In silico evidence for DNA polymerase-beta's substrate-induced conformational
      change.
AB  - Structural information for mammalian DNA pol-beta combined with molecular and
      essential dynamics studies have provided atomistically detailed views of
      functionally important conformational rearrangements that occur during DNA repair
      and replication. This conformational closing before the chemical reaction is
      explored in this work as a function of the bound substrate. Anchors for our study
      are available in crystallographic structures of the DNA pol-beta in "open"
      (polymerase bound to gapped DNA) and "closed" (polymerase bound to gapped DNA and
      substrate, dCTP) forms; these different states have long been used to deduce that
      a large-scale conformational change may help the polymerase choose the correct
      nucleotide, and hence monitor DNA synthesis fidelity, through an "induced-fit"
      mechanism. However, the existence of open states with bound substrate and closed
      states without substrates suggest that substrate-induced conformational closing
      may be more subtle. Our dynamics simulations of two pol-beta/DNA systems
      (with/without substrates at the active site) reveal the large-scale closing
      motions of the thumb and 8-kDa subdomains in the presence of the correct
      substrate--leading to nearly perfect rearrangement of residues in the active site
      for the subsequent chemical step of nucleotidyl transfer--in contrast to an
      opening trend when the substrate is absent, leading to complete disassembly of
      the active site residues. These studies thus provide in silico evidence for the
      substrate-induced conformational rearrangements, as widely assumed based on a
      variety of crystallographic open and closed complexes. Further details gleaned
      from essential dynamics analyses clarify functionally relevant global motions of
      the polymerase-beta/DNA complex as required to prepare the system for the
      chemical reaction of nucleotide extension.

PMID- 15507688
TI  - An all-atom force field for tertiary structure prediction of helical proteins.
AB  - We have developed an all-atom free-energy force field (PFF01) for protein
      tertiary structure prediction. PFF01 is based on physical interactions and was
      parameterized using experimental structures of a family of proteins believed to
      span a wide variety of possible folds. It contains empirical, although sequence
      independent terms for hydrogen bonding. Its solvent-accessible surface area
      solvent model was first fit to transfer energies of small peptides. The
      parameters of the solvent model were then further optimized to stabilize the
      native structure of a single protein, the autonomously folding villin headpiece,
      against competing low-energy decoys. Here we validate the force field for five
      nonhomologous helical proteins with 20-60 amino acids. For each protein, decoys
      with 2-3 A backbone root mean-square deviation and correct experimental Cbeta
      Cbeta distance constraints emerge as those with the lowest energy.

PMID- 15507689
TI  - Functional characterization of a small conductance GIRK channel in rat atrial
      cells.
AB  - Muscarinic K+ (KACh) channels are key determinants of the inhibitory synaptic
      transmission in the heart. These channels are heterotetramers consisting of two
      homologous subunits, G-protein-gated inwardly rectifying K+ (GIRK)1 and GIRK4,
      and have unitary conductance of approximately 35 pS with symmetrical 150 mM KCl
      solutions. Activation of atrial KACh channels, however, is often accompanied by
      the appearance of openings with a lower conductance, suggesting a functional
      heterogeneity of G-protein-sensitive ion channels in the heart. Here we report
      the characterization of a small conductance GIRK (scGIRK) channel present in rat
      atria. This channel is directly activated by Gbetagamma subunits and has a
      unitary conductance of 16 pS. The scGIRK and KACh channels display similar
      affinities for Gbetagamma binding and are frequently found in the same membrane
      patches. Furthermore, Gbetagamma-activated scGIRK channels--like their KACh
      counterparts--exhibit complex gating behavior, fluctuating among four functional
      modes conferred by the apparent binding of a different number of Gbetagamma
      subunits to the channel. The electrogenic efficacy of the scGIRK channels,
      however, is negligible compared to that of KACh channels. Thus, Gbetagamma
      subunits employ the same signaling strategy to regulate two ion channels that are
      apparently endowed with very different functions in the atrial membrane.

PMID- 15507691
TI  - Acute hormonal responses to heavy resistance exercise in strength athletes versus
      nonathletes.
AB  - The aim of the present study was to investigate acute hormonal and neuromuscular
      responses and recovery in strength athletes versus nonathletes during heavy
      resistance exercise performed with the forced and maximum repetitions training
      protocol. Eight male strength athletes (SA) with several years of continuous
      resistance training experience and 8 physically active but non-strength athletes
      (NA) volunteered as subjects. The experimental design comprised two loading
      sessions: maximum repetitions (MR) and forced repetitions (FR). MR included 12-RM
      squats for 4 sets with a 2-min recovery between sets. In FR the initial load was
      higher than in MR so that the subject could lift approximately 8 repetitions by
      himself and 4 additional repetitions with assistance. Before and after the
      loading protocols, blood samples were drawn to determine serum testosterone, free
      testosterone, cortisol and growth hormone concentrations, and blood lactate.
      Maximal voluntary isometric force and EMG activity of the leg extensors was
      measured before and after the loading as well as 24 and 48 hrs after the loading.
      The concentrations of the hormones measured increased significantly (p < .01
      .001) after both loadings in both groups. The responses tended to be higher in FR
      than the MR loading and the increases of testosterone concentrations were
      significantly (p < .01) greater in both loadings in SA than in NA. Both loading
      protocols in both groups also led to neuromuscular fatigue observable with
      significant acute decreases in isometric strength by 32-52% (p < .001) and in
      maximal iEMG (p < .05-01) associated with large increases in blood lactate. These
      data suggest that, at least in experienced strength athletes, the forced
      repetition protocol is a viable alternative to the more traditional maximum
      repetition protocol and may even be a superior approach.

PMID- 15507690
TI  - Field-dependent effect of crown ether (18-crown-6) on ionic conductance of alpha
      hemolysin channels.
AB  - Closing linear poly(ethylene glycol) (PEG) into a circular "crown" dramatically
      changes its dynamics in the alpha-hemolysin channel. In the electrically neutral
      crown ether (C2H4O)6, six ethylene oxide monomers are linked into a circle that
      gives the molecule ion-complexing capacity and increases its rigidity. As with
      linear PEG, addition of the crown to the membrane-bathing solution decreases the
      ionic conductance of the channel and generates additional conductance noise.
      However, in contrast to linear PEG, both the conductance reduction (reporting on
      crown partitioning into the channel pore) and the noise (reporting on crown
      dynamics in the pore) now depend on voltage strongly and nonmonotonically. Within
      the whole frequency range accessible in channel reconstitution experiments, the
      noise power spectrum is "white", showing that crown exchange between the channel
      and the bulk solution is fast. Analyzing these data in the framework of a
      Markovian two-state model, we are able to characterize the process
      quantitatively. We show that the lifetime of the crown in the channel reaches its
      maximum (a few microseconds) at about the same voltage (approximately 100 mV,
      negative from the side of protein addition) where the crown's reduction of the
      channel conductance is most pronounced. Our interpretation is that, because of
      its rigidity, the crown feels an effective steric barrier in the narrowest part
      of the channel pore. This barrier together with crown-ion complexing and
      resultant interaction with the applied field leads to behavior usually associated
      with voltage-dependent binding in the channel pore.

PMID- 15507692
TI  - Cardiopulmonary physiology and responses of ultramarathon athletes to prolonged
      exercise.
AB  - The purpose of this study was to determine the changes of pulmonary function and
      autonomic cardiovascular control after an ultramarathon and their relation to
      performance. Eight entrants to the Canadian National Championship 100-km running
      race participated in the study. Pulmonary function and 30-s maximum voluntary
      ventilation (MVV30s) tests were conducted one day before the race and within 5
      minutes of race completion. Heart rate and blood pressure data were collected 30
      min before and 5 min after the race as well as during a 10-min stand test one day
      prior to the race. During the race, beat-by-beat R-R interval data were collected
      over the first and last 20 km. The results showed that MVV30s and MVV30s tidal
      volumes were reduced postrace (p < 0.001). Prerace supine total harmonic
      variation (p < 0.01) and prerace MVV values (10 s to 30 s) (p < 0.05) were
      correlated with race finish time. The changes in pulmonary function and MVV30s
      values from pre- and postrace were not significantly correlated to race
      performance. We conclude that maximal sustainable ventilatory power and dynamic
      autonomic cardiovascular control are important factors in determining overall
      performance in an ultramarathon.

PMID- 15507693
TI  - Ventilatory threshold characterizations during incremental rowing and cycling
      exercises in older subjects.
AB  - In order to individualize the intensity of an aerobic training program on
      different ergometers in healthy elderly subjects using a single test of muscular
      exercise, we analysed cardiorespiratory responses in 8 men (65.7 +/- 4.5 yrs) and
      10 women (63.3 +/- 4.8 yrs). The heart rate corresponding to the ventilatory
      threshold was defined as individualised exercise intensity. All subjects carried
      out two incremental exercise tests on the cycle and rowing ergometers. For men,
      the results on the cycle ergometer and rowing ergometer demonstrated that, at
      ventilatory threshold, heart rates were not significantly different (114.6 +/-
      13.7 and 115.6 +/- 14.2 beats x min (-1), respectively), but ventilation was
      significantly higher in rowing (p < 0.05). At ventilatory threshold, heart rates
      for women were not significantly different between the cycle ergometer and rowing
      ergometer (121.3 +/- 12.4 and 125.1 +/- 15.2 beats x min (-1 ), respectively),
      but ventilation was significantly higher in rowing (p< 0.01). At maximal
      exercise, maximal tidal volume for men (p < 0.01) and women (p < 0.05) was
      significantly higher in rowing. In spite of alterations of breathing patterns on
      the rowing ergometer, it is possible to design an individualized training program
      for healthy elderly subjects based on a single muscle evaluation exercise in
      order to diversify and optimize the cardiorespiratory benefits following an
      aerobic training program.

PMID- 15507694
TI  - Effects of an external nasal dilator on athletic performance of male adolescents.
AB  - This study examined the effect of an external nasal dilator strip (ENDS) on three
      field tests of maximal performance and monitored the rating of perceived
      breathing effort (RPBE). Thirty male Chinese students (age 15.2 +/- 1.6 yrs)
      performed three maximal field tests: (a) short-term anaerobic power (SAnP: 40-m
      sprint); (b) long-term anaerobic power (LAnP: shuttle sprint); and (c) peak
      aerobic performance (AeP: multistage 20-m shuttle run) under three conditions:
      ENDS, placebo, and control. Students were randomly placed into 6 groups using a
      fully counterbalanced single-blind design. No significant differences were seen
      between conditions in the anaerobic performances measured by SAnP and LAnP.
      However, the ENDS produced a significant improvement in peak aerobic performance
      (p = 0.037) compared to the control condition of 3.2% (95% CI= 6.2-0.2; Cohen
      effect size = 0.2), and also compared to the placebo condition (p = 0.018) of
      2.9% (95% CI = 5.1-0.2; Cohen effect size =0.2). The ENDS condition also
      significantly reduced RPBE during the AeP and LAnP tests by an average of 5.5%
      and 3.8%, respectively. Wearing an external nasal dilator can significantly
      reduce breathing effort and improve peak aerobic performance during field tests
      involving maximal running.

PMID- 15507695
TI  - Effect of exercise timing on postprandial lipemia in hypertriglyceridemic men.
AB  - We investigated the effect of exercise timing on attenuation of postprandial
      hyper-triglyceridemia (PHTG) in individuals with hypertriglyceridemia (HTG).
      Subjects were 10 males (TG = 290.1 +/- 28.5 mg/dl). Each subject performed a
      control trial (Ctr), 12-hr premeal exercise trial (12-hr Pre), and 24-hr premeal
      exercise trial (24-hr Pre). In each trial, subjects had a fat-rich meal. In the
      exercise trials they jogged on a treadmill at 60% of their VO2max for 1 hr at a
      designated time. Blood samples were taken at 0 (immediately before the fat meal),
      and at 2, 4, 6, 8, and 24 hrs after the meal. The results indicated that plasma
      TG concentrations in 12-hr Pre were lower than in Ctr and 24-hr Pre (p < 0.03).
      The area score under the TG concentration curve (TG AUC score) in 12-hr Pre was
      37% and 33% lower than in 24-hr Pre and Ctr (p < 0.02), respectively. Insulin
      concentrations in 12-hr Pre were lower than Ctr and 24-hr Pre (p < 0.001). The
      plasma nonesterified fatty acid (NEFA) concentration was higher in 12-hr Pre than
      in both 24-hr Pre and Ctr (p < 0.003). There were no trial differences in both
      HDLtot-Ch and HDL2-Ch. These results suggest that exercising 12 hrs prior to a
      fat-meal intake significantly reduces PHTG response whereas exercising 24 hrs
      prior to the meal does not attenuate PHTG in hypertriglyceridemic men. The effect
      of an acute exercise bout on PHTG lowering may be short-lived and diminished by
      24 hrs.

PMID- 15507696
TI  - Fatty acids and exercise affect glucose transport but not tumour growth in F-344
      rats.
AB  - This study examined the effect of diet and exercise on tumour growth, and the
      effect of dietary fatty acids on glucose uptake. Male Fischer 344 rats were
      divided into 4 dietary groups and fed for 2 weeks. The diets were 5% (wt/wt)
      safflower oil, 10% safflower oil, 5% docosahexaenoic acid(DHA)-rich, and 10% DHA
      rich. On Day 14 the animals were injected with rat fibrosarcoma tumour cells.
      After 3 days of tumour growth the animals in each diet group were divided into
      exercise and nonexercise groups. Exercise was achieved by voluntary wheel
      running. Dietary intake, body weight, tumour growth, and distance run were
      determined daily. Two weeks later the animals were euthanized and the following
      tissues were dissected out: tumour, liver, heart, epididymal fat pads,
      gastrocnemius, epitrochlearis, and soleus muscles. Glucose transport experiments
      were performed on the epitrochlearis and soleus muscles whereas phospholipid
      analysis was completed on the gastrocnemius muscle. We observed no effect of
      either diet or exercise on tumour growth. The glucose transport data demonstrates
      that short-term voluntary running can cause increased insulin-sensitive transport
      and that DHA may inhibit transport. DHA-containing diets were associated with
      increased oxidation products TBARM. In conclusion, exercise benefits on glucose
      disposal are maintained in tumour-bearing animals but are influenced by fat
      content and composition. High DHA diets may also increase oxidative damage in
      muscle through enhanced TBARM production.

PMID- 15507697
TI  - Viral detection.
AB  - The focus of this chapter is the detection of DNA viruses. The emphasis is on
      amplification reactions that include reverse transcription-polymerase chain
      reaction (RT-PCR), PCR, real-time RT-PCR, and real-time PCR methods.
      Amplification of the E6 and E7 oncoproteins of HPV16 is described in detail, and
      primers and probes that can be used to amplify these oncogenes are described.
      Techniques to quantify these oncogenes in infected human tissue specimens are
      presented, and analysis of data resulting from real-time PCR detection of the E6
      and E7 oncogenes is discussed. Other methods for viral nucleic acid detection,
      including nested PCR amplification, ligase chain reaction, and enzyme-linked
      immunosorbent assay (ELISA), are also briefly discussed.

PMID- 15507698
TI  - Quantitative detection of Epstein-Barr virus DNA in clinical specimens by rapid
      real-time PCR targeting a highly conserved region of EBNA-1.
AB  - Here we describe a LightCycler-based real-time PCR for quantitative detection of
      EBV DNA in clinical samples such as unfractionated whole blood, serum, or plasma.
      This assay is based on amplification of a highly conserved 213-bp region of the
      EBNA-1 gene, a single-copy gene of EBV required for maintenance of the EBV genome
      within the infected host cell. For real-time detection of amplicons, two internal
      hybridization probes are added, labeled with the fluoregenic dyes fluorescein and
      LCRed640, respectively. Simultaneous hybridization of these probes to the
      amplification products brings them in close proximity. Subsequent excitation of
      the fluorescein label by filtered excitation light from a light source in the
      LightCycler device will lead to fluorescence energy transfer (FRET) from the
      fluorescein label to the LCRed640 label. The light emitted from the LCRed640
      label is then measured and correlates to the amount of product generated. The
      cycle at which the fluorescence exceeds the background is designated the
      threshold cycle. By comparing the threshold cycle of a clinical specimen with
      those of standard curve samples, the amount of EBV DNA in clinical samples can be
      determined. This real-time PCR approach is extremely rapid owing to efficient
      heat conduction by using glass capillaries, small reaction volumes, and air as
      heating medium. The "closed-tube" system eliminates the risk of PCR contamination
      by product carryover and also the need for post-PCR detection.

PMID- 15507699
TI  - Profiling of Epstein-Barr virus latent RNA expression in clinical specimens by
      gene-specific multiprimed cDNA synthesis and PCR.
AB  - We describe a two-step RT-PCR method for simultaneous detection of EBNA-1 (QK and
      Y3K splice variants), EBNA-2, LMP-1, LMP-2a and -2b, ZEBRA, and BARTs RNA encoded
      by Epstein-Barr virus. As a control for RNA integrity, the low-copy-number
      transcript derived from U1A snRNP, a cellular housekeeping gene, is coamplified.
      Copy DNA (cDNA) for these nine targets is simultaneously synthesized in a gene
      specific, multiprimed cDNA reaction, which strongly reduces the amount of
      required clinical specimen and allows more sensitive detection than random
      hexamer or oligo-dT priming. For amplification, cDNA synthesis is followed by
      nine separate PCRs for the mentioned targets. Primers were designed either as
      intron-flanking, to avoid background DNA amplification, or in different exons,
      allowing identification of differentially spliced RNA molecules. To increase
      specificity, PCR products are detected by autoradiography after hybridization
      with radiolabeled internal oligonucleotide probes. The method described is highly
      suitable for profiling EBV latent RNA expression in tissue biopsies, cultured or
      isolated cells, and unfractionated whole blood and for definition of EBV latency
      type I, II, or III gene expression in these samples.

PMID- 15507700
TI  - Quantitative detection of viral gene expression in populations of Epstein-Barr
      virus-infected cells in vivo.
AB  - The method described in this chapter uses limiting dilution analysis in
      conjunction with RT-PCR to determine quantitatively what percentage of EBV
      infected cells within a given population are expressing the viral genes EBNA-1 Q
      K, EBNA-2, LMP-1, LMP-2, BZLF-1, and the EBERs. Because this technique involves
      limiting dilution analysis, it is possible to define which viral transcription
      programs are being used at the single-cell level. This assay takes 3-4 d to
      complete and involves the following steps: (1) sample preparation and isolation
      of the cell population of interest; (2) DNA-PCR limiting dilution analysis to
      determine the frequency of infected cells within the cell population; (3) RNA
      isolation; (4) cDNA synthesis; (5) PCR; (6) visualization of PCR products by
      Southern blotting; and (7) calculations. As an example, we have used PBMCs from
      the blood of an acute infectious mononucleosis patient. However, this technique
      can be applied to other cell populations, such as B cells, and other patient
      groups, such as healthy long-term virus carriers and immunosuppressed organ
      transplant recipients.

PMID- 15507701
TI  - Detection and quantification of the rare latently infected cell undergoing herpes
      simplex virus transcriptional activation in the nervous system in vivo.
AB  - Herpes simplex virus (HSV), in contrast to most other members of the herpes virus
      family, has the ability to infect, enter latency, and reactivate from latency in
      a number of nonhuman species, including mice. This provides a unique opportunity
      to study the complex lytic-latent cycle of a human neurotropic virus in a mouse
      model. This chapter details basic methods for inducing and quantifying
      reactivation, with emphasis on the first strategy for detecting and quantifying
      the initiation of HSV reactivation in vivo.

PMID- 15507702
TI  - Reporter cell lines for the detection of herpes simplex viruses.
AB  - Virus culture has played significant roles in basic and clinical virology, with a
      number of advantages that cannot be attainable by modern molecular techniques.
      However, virus culture is generally a slower process, as it inevitably takes the
      period of a full replication cycle of a given virus. A genetically modified cell
      culture with a virus-inducible marker is described here, using a frequently
      isolated DNA virus (herpes simplex virus) as a model. The assay system relies on
      expression of the reporter gene driven by a specific viral promoter that is
      triggered early in the course of viral infection. The reporter gene employed was
      green fluorescent protein (GFP) or secreted alkaline phosphatase (SEAP), whose
      assays offer real-time detection or quantification, respectively. This cell-based
      assay is simple, rapid, sensitive, specific, and quantitative and serves as a
      phenotypic method for determination of antiviral susceptibilities.

PMID- 15507703
TI  - Unraveling the architecture of viruses by high-resolution atomic force
      microscopy.
AB  - Atomic force microscopy (AFM) has recently emerged as an effective complement to
      other structure determination techniques for studying virus structure and
      function. AFM allows the direct visualization of viruses in a hydrated state and
      can probe surface topography in unrivaled detail. Moreover, AFM can be used to
      elucidate dynamic processes associated with the life cycle of viruses in vitro.
      It can readily produce high-resolution, nonaveraged, single-particle images of
      both polymorphic and pleiomorphic viruses. Although AFM does not yield images of
      internal structures within an intact virion as do penetrating techniques such as
      electron microscopy and X-ray crystallography, nonetheless, by visualizing the
      surfaces of internal structures upon treatment with chemical and enzymatic
      agents, as we demonstrated recently with vaccinia virus, modeling of the complex
      architecture of a large virus is possible.

PMID- 15507704
TI  - Studying the structure of large viruses with multiresolution imaging.
AB  - Multiresolution imaging is an extremely useful technique for understanding in
      detail the structure of large DNA viruses that do not yield to the requirements
      of protein crystallography. The methodology consists in fitting the atomic
      structures of capsid components, independently solved, to medium-resolution, 3D
      maps of the complete virion, obtained by cryoelectron microscopy and image
      processing. On combining the two kinds of imaging data, one must take into
      account their intrinsic differences, as they have different resolution, suffer
      from different imaging artifacts, and are at different scales. These efforts are
      rewarded by "quasi-atomic" resolution models that provide valuable information
      about protein-protein interactions in the capsid. Difference maps calculated by
      subtracting the quasi-atomic model from the cryoelectron microscopy map reveal
      the molecular envelope of those capsid components whose atomic structure is
      unknown. A better understanding of the complex interactions involved in capsid
      assembly, stabilization, and disassembly is thus achieved.

PMID- 15507705
TI  - Herpes simplex virus-cell interactions studied by low-fading contrasted
      immunofluorescence.
AB  - The low-fading immunofluorescence with propidium iodide contrast described here
      is recommended for light and confocal viral antigen identification and other cell
      biology studies because: (1) it is a simple, rapid, sensitive, and reproducible
      technique; (2) phase-contrast microscopy is unnecessary; (3) contrast is optimal
      without blurring the fluorescent labeling; (4) autofluorescence is minimal, even
      in fixed cells; (5) background staining is minimal; (6) fading is invisible for
      at least 5-min exposures, even in preparations with weak antigen presentation;
      (7) fluorescence is stable after storage in the dark at -20 degrees C; (8)
      fluorochromes are small-sized markers without steric hindrance; and (9) there is
      no need for silver enhancement or substrate solutions, which increase the risk of
      diffusion and other artifacts.

PMID- 15507706
TI  - Herpes simplex virus-cell interactions studied by immunogold cryosection electron
      microscopy.
AB  - A technique is presented for high-resolution postembedding immunolocalization of
      one or two (or several) antigens in the same ultrathin cryosection using primary
      monoclonal antibodies from the same species. The optimized three-layer indirect
      immunogold-labeled cryosection electron microscopy described is recommended for
      studies of virus-cell interactions, because: (1) it is a simple and reproducible
      method; (2) colloidal gold markers are electron-dense, stable, and easy to
      recognize; (3) the membraneous ultrastructure and immunolabeling are well
      preserved; (4) immunolabeling is less in the two-layer method; (5) silver
      enhanced gold particles vary in size and shape; (6) it is possible to demonstrate
      herpes simplex virus type 1 glycoproteins gC-1 and gD-1 in the nuclear membranes
      and gC-1- and gD-1-labeled viral particles in the perinuclear space and to
      observe virions in the endoplasmic reticulum and Golgi area. The use of buffered
      3% paraformaldehyde plus 2% glutaraldehyde for 2 h at room temperature
      effectively destroys free anti-IgG binding sites on the secondary antibodies in
      double-labeling immunogold cryosection electron microscopy and is recommended
      because: (1) inactivation is obtained through buffered primary fixative; (2) the
      method is simple and reproducible; (3) cross-labeling is effectively avoided; (4)
      silver-intensification, high temperature, and methyl cellulose cover of ultrathin
      cryosections are avoided between the staining sequences; and (5) ultrastructure
      and antigenicity are well preserved.

PMID- 15507707
TI  - FTIR microscopy detection of cells infected with viruses.
AB  - Fourier-transform infrared (FTIR) microscopy is considered 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 a cell culture or a tissue. We have shown
      that it is possible to apply FTIR microscopy as a sensitive and effective assay
      for the detection of cells infected with various members of the herpes family of
      viruses and retroviruses. Detectable and significant spectral differences between
      normal and infected cells were evident at early stages of the infection.
      Impressive changes in several spectroscopic parameters were seen in infected
      compared with uninfected cells. It seems that the change in spectral behavior is
      specific to the infecting virus, because cells infected with herpesviruses showed
      different spectral changes compared with cells infected with retroviruses.

PMID- 15507708
TI  - The JC virus-like particle overlay assay.
AB  - JC virus (JCV) belongs to the family of double-stranded DNA polyomaviruses and in
      humans causes a demyelinating disease of the central nervous system, progressive
      multifocal leukoencephalopathy (PML). It has been reported that sialic acids play
      a pivotal role in hemagglutination of red blood cells and entry into host cells
      of JCV and that JCV can enter a wide variety of cell types and localize to the
      nuclei. The outer shell of the JCV virion comprises the major capsid protein VP1,
      and a virus-like particle (VLP) consisting of recombinant VP1 made from
      Escherichia coli exhibit a virion-like structure and physiological functions
      (cellular attachment and intracytoplasmic trafficking) similar to those of JCV
      virions. To examine the mechanism of cell attachment of JCV, an overlay assay
      using a VLP has been developed, revealing that sialoglycoproteins, including
      alpha1 acid-glycoprotein, fetuin, and transferrin receptor bind with VLP. In
      addition, VLPs bind to glycolipids, such as lactosylceramide and gangliosides
      including GM3, GD2, GD3, GD1b, GT1b, and GQ1b, and VLP weakly bind to GD1a. In
      this section, detailed procedures for the synthesis of VLP from E. coli and VLP
      overlay assay are described.

PMID- 15507709
TI  - Analysis of fusion using a virus-free cell fusion assay.
AB  - For enveloped viruses, such as viruses within the herpesvirus family, of which
      Epstein-Barr virus (EBV) is a member, infection of target cells includes two
      distinct steps. The first is characterized by the binding of viral envelope
      glycoproteins to host cellular receptors. After binding, the viral membrane and
      the cellular membrane fuse. Without both binding and fusion, the virus is not
      able to enter the host target cell efficiently. Combined with the specific
      tropism of EBV for primarily two cell types, B lymphocytes and epithelial cells,
      and the difficulty in inducing lytic replication of EBV in vitro, there is a lack
      of a good experimental model to study EBV-induced viral fusion. To study fusion
      more efficiently and effectively, we have employed a virus-free cell-cell fusion
      assay. In the effector cell, the viral glycoproteins and a plasmid containing the
      T7 promoter, driving the luciferase gene, are expressed. In the target cell type,
      T7 RNA polymerase is transfected. Fusion is quantitated by the amount of
      luciferase expression after mixing of the two cell types. Alongside the fusion
      assay, a CELISA is performed to determine glycoprotein expression on the effector
      cells. This methodology has been useful in studying membrane fusion induced by
      other herpesvirus family members.

PMID- 15507710
TI  - Pseudovirions as specific tools for investigation of virus interactions with
      cells.
AB  - This chapter outlines the generation and application of human papillomavirus type
      33 (HPV33) pseudovirions. The method describes (1) the construction of vaccinia
      viruses recombinant for the major and minor HPV capsid proteins, L1 and L2,
      respectively; (2) the transfection of Cos7 cells with a marker plasmid
      replicating to high copy numbers; (3) the expression of L1 and L2 using the
      vaccinia virus expression system; (4) the extraction, purification, and analysis
      of HPV33 pseudovirions; and (5) their use in pseudoinfection assays. These
      pseudovirions are structurally indistinguishable from native virions and are
      therefore valuable tools for the study of papillomavirus-cell interactions. The
      methods described can be adopted for other nonenveloped DNA viruses and may be
      useful for gene transfer.

PMID- 15507711
TI  - Simultaneous in situ detection of RNA, DNA, and protein using tyramide-coupled
      immunofluorescence.
AB  - The use of tyramide-coupled immunofluorescence at the single cell level provides
      expedient, clean, and sensitive signals for detection of DNA, RNA, or proteins.
      The principle is based on the ability of horseradish peroxidase (HRP) to cleave
      tyramides into a free radical species with a very short diffusion radius. The
      free radicals are then covalently bound to electron-rich moieties such as
      tyrosine in proteins proximal to the targets. Here we present protocols for
      tyramide fluorescent in situ hybridization (T-FISH), which detects unique DNA
      species using DNA probes as short as approx 300-500 bp, or unique RNA species
      with probes as small as an oligonucleotide. We also present a protocol for
      tyramide immunofluorescence (T-IF) to detect protein antigens. By combining these
      protocols with several tyramide-coupled fluorophores, multiple targets can be
      detected simultaneously in situ, which is ideal for in-depth analyses at the
      molecular and cellular levels. Finally, we describe the detection of nascent
      viral RNA transcripts simultaneously with integrated viral genomes or chromosomal
      domains in single cells or tissue sections.

PMID- 15507712
TI  - Identification and characterization of herpesviral immediate-early genes.
AB  - Immediate-early (IE) genes are the first class of viral genes expressed after
      primary infection or reactivation. As transcription of IE genes does not require
      prior viral protein synthesis, this class of genes is experimentally defined by
      their transcription following primary infection or reactivation in the presence
      of inhibitors of protein synthesis. This chapter describes an approach to
      identify IE genes in a novel herpesvirus genome. Transcription of IE genes is
      selectively induced with sodium butyrate in the presence of the protein synthesis
      inhibitor cycloheximide. The transcripts of the induced genes are identified by
      using a cDNA subtraction-based method of gene expression screening.

PMID- 15507713
TI  - Methods for measuring the replication and segregation of Epstein-Barr virus-based
      plasmids.
AB  - Plasmids containing the Epstein-Barr virus (EBV) latent origin of replication,
      OriP, are stably maintained in human cells expressing the viral EBNA-1 protein.
      This stable maintenance is owing to the ability of EBNA-1 to activate DNA
      replication from OriP and to facilitate the segregation of the plasmids during
      cell division. Methods for quantifying the replication and stable maintenance of
      EBV-based plasmids in human cells are presented here, as is a reconstituted
      segregation system in yeast that enables the segregation activity of EBNA1 to be
      measured independently from its replication activity.

PMID- 15507714
TI  - DNA affinity purification of Epstein-Barr virus OriP-binding proteins.
AB  - DNA affinity purification has been used to identify cellular and viral proteins
      associated with the Epstein-Barr virus origin of plasmid DNA replication. This
      approach allows for a one- or two-step purification scheme of high-affinity DNA
      binding proteins from crude nuclear extracts. Additionally, this approach may be
      useful for isolation of proteins that are found in the insoluble fractions of the
      nuclear matrix or scaffold.

PMID- 15507715
TI  - Pre-B-cell colony formation assay.
AB  - Latent membrane protein 2A (LMP-2A) of Epstein-Barr virus (EBV) mimics a
      constitutively active B-cell receptor (BCR) and plays a key role in viral latency
      and EBV pathogenesis. By functioning as a BCR mimic, LMP-2A drives B-cell
      development, resulting in the bypass of normal B-cell developmental checkpoints.
      To assess the function of LMP-2A, we have utilized a colony formation assay for
      the progenitor B cells that uses the B-cell proliferation factor IL-7.

PMID- 15507716
TI  - Luciferase real-time bioluminescence imaging for the study of viral pathogenesis.
AB  - Herpes simplex virus 1 (HSV-1) is a common and significant neurotropic human
      pathogen that infects 80% of all persons by adulthood. During acute HSV-1
      infection, virus replicates peripherally in epithelia, enters axonal terminals,
      and is transported retrogradely to sensory nerve ganglia, where HSV-1 may
      establish latency or progress to life-threatening infection of the central
      nervous system. Studies of viral and host factors that influence pathogenesis
      have largely used experimental mouse models that rely on sacrifice of infected
      mice to determine distribution and titer of virus. Although this experimental
      paradigm has provided important data, it precludes real-time investigations of
      the same animal over the entire course of disease progression. This limits
      potentially significant insights from animal-to-animal variations in host
      pathogen relationships. Unexpected sites of infection also may be missed because
      appropriate tissues are not analyzed for virus. To improve investigations of
      viral and host factors that determine HSV-1 pathogenesis, we have validated
      bioluminescence imaging (BLI) as a technique to monitor infection with a
      recombinant strain KOS HSV-1 virus that expresses firefly luciferase (FL). This
      imaging technique allows repetitive, noninvasive monitoring of HSV-1 in living
      mice. In this chapter, we describe the protocols that we use for in vivo BLI of
      HSV-1 infection.

PMID- 15507717
TI  - Culturing primary and transformed neuronal cells for studying pseudorabies virus
      infection.
AB  - This chapter discusses the culture of primary sympathetic neurons (superior
      cervical ganglia) from rat embryos and PC12 cells differentiated into neurons for
      use in viral infection experiments. Methods are described for the use of a
      neurotropic herpesvirus, pseudorabies virus (PRV), to analyze the assembly,
      egress, and transport of viral antigens in neurons.

PMID- 15507718
TI  - Human papillomavirus type 31 life cycle: methods for study using tissue culture
      models.
AB  - The life cycle of human papillomaviruses (HPVs) has been difficult to study in
      tissue culture owing to its dependence on epithelial differentiation. In this
      chapter several methods are described to imitate the important steps in the HPV
      life cycle. Normal human keratinocytes (NHKs) harvested from neonatal foreskins
      were transfected with HPV type 31 genomes in order to generate stable cell lines
      containing episomal copies of HPV genomes. HPV-positive keratinocyte cultures
      were maintained in E medium in the presence of mitomycin C-treated J2 3T3
      fibroblast feeders. Finally, the keratinocytes were induced to undergo epithelial
      differentiation in semisolid medium to provoke viral late functions like genomic
      amplification and late transcription.

PMID- 15507719
TI  - Molecular genetics of herpesviruses: a recombinant technology approach.
AB  - Herpesvirus genetics have long been hindered by the large size of the typical
      herpesvirus genome and the consequent recalcitrance of these genomes to
      manipulation by standard molecular genetics techniques. However, two primary
      strategies have emerged that allow for the generation of targeted viral mutants.
      With these mutants, investigators can pursue critical questions regarding the
      relationship between specific viral genetic elements and the viral life cycle.
      The first strategy of viral genome manipulation utilizes the mammalian homologous
      recombination machinery to introduce specific changes into the native viral
      genome. This approach involves construction of a targeting vector containing both
      the desired mutation and a significant flanking viral sequence to permit
      efficient recombination. The targeting vector is then introduced into mammalian
      cells, along with viral DNA, and recombinant virus is subsequently selected,
      harvested, and purified. The second, and more recent, approach utilizes bacterial
      artificial chromosome (BAC) technology to reconstitute complete herpesvirus
      genomes in the context of a prokaryote, E. coli. This artificial genome is then
      manipulated in, and purified from, E. coli before introduction into a mammalian
      background in which viral phenotypes can be assessed. Both strategies are
      discussed in this review, with particular emphasis on the homologous
      recombination strategies that have continued to be a powerful genetic tool in
      many herpesvirus systems.

PMID- 15507720
TI  - Molecular genetics of DNA viruses: recombinant virus technology.
AB  - Recombinant viral genomes cloned onto BAC vectors can be subjected to extensive
      molecular genetic analysis in the context of E. coli. Thus, the recombinant virus
      technology exploits the power of prokaryotic genetics to introduce all kinds of
      mutations into the recombinant genome. All available techniques are based on
      homologous recombination between a targeting vector carrying the mutated version
      of the gene of interest and the recombinant virus. After modification, the mutant
      viral genome is stably introduced into eukaryotic cells permissive for viral
      lytic replication. In these cells, mutant viral genomes can be packaged into
      infectious particles to evaluate the effect of these mutations in the context of
      the complete genome.

PMID- 15507721
TI  - Genetic analysis of cytomegalovirus by shuttle mutagenesis.
AB  - The genomes of Herpesviridae family members are among the largest of all viruses
      and therefore present a formidable challenge in understanding the roles of every
      gene in replication or pathogenesis. For example, murine cytomegalovirus (MCMV)
      has a genome of 230 kb that encodes more than 170 genes, many of which have
      unknown functions. Many techniques for the genetic analysis of a herpesvirus have
      been developed over the past two decades. One such procedure involves the use of
      a shuttle mutagenesis system, and it has successfully generated a pool of MCMV
      mutants that contained an engineered Tn3-type transposon inserted within their
      genome. The process of shuttle mutagenesis involves the construction of a genomic
      fragment library, transposon mutagenesis of the library, and generation of virus
      mutants through homologous recombination. This chapter details the methodologies
      required for implementing a Tn3-based shuttle mutagenesis system for construction
      of a mutant virus library.

PMID- 15507722
TI  - Construction of a gene inactivation library for Bovine herpesvirus 1 using
      infectious clone technology.
AB  - The application of infectious clone technology to herpesvirus biology has
      revolutionized the study of these viruses. Previously the ability to manipulate
      these large DNA viruses was limited to methods dependent on homologous
      recombination in mammalian cells. However, the construction of herpesvirus
      infectious clones using bacterial artificial chromosome vectors has permitted the
      application of powerful bacterial genetics for the manipulation of these viruses.
      A method is described for the construction and characterization of a gene
      inactivation library of Bovine herpesvirus 1 using an infectious clone. The
      method utilizes transposon-mediated gene inactivation, which permits gene
      inactivation without any prior knowledge of the viral genomic sequence.
      Furthermore, as the genetic manipulation is performed in bacteria the
      inactivation of those viral genes that are essential for viral replication is
      also possible. The method described here can be readily applied to any
      herpesvirus clone and provides the tools for precise characterization of all the
      genes contained within a herpesvirus genome.

PMID- 15507723
TI  - Selective silencing of viral gene E6 and E7 expression in HPV-positive human
      cervical carcinoma cells using small interfering RNAs.
AB  - The newly discovered phenomenon of RNA interference (RNAi) offers the dual
      facility of selective viral gene silencing coupled with ease of tailoring to meet
      genetic variation within the viral genome. Such promise identifies RNAi as an
      exciting new approach to treat virus-induced diseases, including virus-induced
      cancers. RNAi can be induced using small interfering RNA (siRNA). Synthetic siRNA
      targets homologous mRNA for degradation, and this process is highly efficient.
      Using cervical cancer cells as a model, we demonstrate RNAi for viral oncogenes.
      Cervical cancer is the second most common cancer in women worldwide and is caused
      by human papillomavirus (HPV). Silencing of HPV E6 and E7 gene expression was
      achieved using siRNAs to target the respective viral mRNAs. E6 silencing induced
      accumulation of cellular p53 protein, transactivation of the cell cycle control
      p21 gene, and reduced cell growth. By contrast, E7 silencing induced apoptotic
      cell death. HPV-negative cells appeared to be unaffected by the antiviral siRNAs.
      Thus siRNA can induce selective silencing of exogenous viral genes in mammalian
      cells, and the process does not interfere with the recovery of cellular
      regulatory systems previously inhibited by viral gene expression.

PMID- 15507724
TI  - Design of a herpes simplex virus type 2 long oligonucleotide-based microarray:
      global analysis of HSV-2 transcript abundance during productive infection.
AB  - The design and construction of a long (75-mer) oligonucleotide-based DNA
      microarray for herpes simplex virus type 2 transcripts is described. This array
      is utilized to generate an analysis of HSV-2 transcript abundance as a function
      of conditions of infection of human cells, and global patterns of HSV-2
      transcript abundance are compared with those for HSV-1. General similarities in
      patterns along with notable differences in specific details are noted. These
      results reveal a marked conservation in the program of gene activity between
      phenotypically diverged strains.

PMID- 15507725
TI  - Real-time quantitative PCR analysis of viral transcription.
AB  - Whole-genome profiling using DNA arrays has led to tremendous advances in our
      understanding of cell biology. It has had similar success when applied to large
      viral genomes, such as the herpesviruses. Unfortunately, most DNA arrays still
      require specialized and expensive resources and, generally, large amounts of
      input RNA. An alternative approach is to query entire viral genomes using real
      time quantitative PCR. We have designed such PCR-based arrays for every open
      reading frame of human herpesvirus 8 and describe here the general design
      criteria, validation procedures, and detailed application to quantify viral
      mRNAs. This should provide a useful resource either for whole-genome arrays or
      just to measure transcription of any one particular mRNA of interest. Because
      these arrays are RT-PCR-based, they are inherently more sensitive and robust than
      current hybridization-based approaches and are ideally suited to query viral gene
      expression in models of pathogenesis.

PMID- 15507726
TI  - Rapid screening of chemical inhibitors that block processive DNA synthesis of
      herpesviruses: potential application to high-throughput screening.
AB  - Processivity factors associate with DNA polymerases, enabling them to incorporate
      thousands of nucleotides without dissociating from the template. The processivity
      factors encoded by each of the herpesviruses are ideal targets for specifically
      blocking viral replication, particularly since they have unique primary amino
      acid sequences. Here we provide details of a rapid mechanistic plate assay and
      its potential application to high-throughput screening of libraries of tens of
      thousands of chemical compounds to identify inhibitors of processive DNA
      synthesis. Methods of validation testing are presented.

PMID- 15507727
TI  - Occurrence of Salmonella Enteritidis phage type 29 in Austria: an opportunity to
      assess the relevance of chicken meat as source of human Salmonella infections.
AB  - Assuming that the various phage types of Salmonella Enteritidis (S. Enteritidis)
      are largely equally virulent, the importance of certain foods as sources of
      infection for human salmonellosis can be deduced from differences in the
      distribution of phage types in human and non-human samples. In 2002, S.
      Enteritidis phage type 29 (PT29) was first isolated from non-human test samples
      in Austria. S. Enteritidis PT29 accounted for 44 (27.7%) of 159 S. Enteritidis
      strains, derived from veterinary samples of chicken (e.g. meat, giblets) or
      chicken habitations (e.g. swabs from the coop and excrement). At the food retail
      level (chicken meat, chicken liver), five (13.1%) of 38 S. Enteritidis isolates
      were PT29. The proportion of S. Enteritidis PT29 in human samples was much lower.
      Only 0.4% (30 human primary isolates) of all S. Enteritidis isolates in the year
      2002, and 0.33% (23 human primary isolates) of all human S. Enteritidis strains
      in 2003 were PT29. In our opinion, the discrepancy between the high prevalence of
      S. Enteritidis PT29 in broilers and chicken meat and the low number of PT29 cases
      in humans indicates that chicken meat of Austrian origin is currently only a
      minor source of human S. Enteritidis infections.

PMID- 15507728
TI  - Preliminary results from the new HIV surveillance system in France.
AB  - In addition to AIDS surveillance, data on HIV infection are necessary to better
      follow the dynamics of the epidemic. We report the first results of France's
      mandatory anonymous HIV notification system, which is linked to a virological
      surveillance of recent HIV infections and of circulating HIV types, groups and
      subtypes. HIV notifications are initiated by microbiologists who create an
      anonymous code of patient's identity. Clinicians complete the notification form
      with epidemiological and clinical data. Notifications are sent to the local
      health authorities and passed to the Institut de Veille Sanitaire (InVS).
      Laboratories voluntarily send sera from newly diagnosed HIV infected persons on
      dried blood spots to the national HIV reference laboratory where an immunoassay
      for recent infection (< or = 6 months) and a serotyping assay for the
      determination of group and subtype are done. The virological results are then
      merged at the InVS with the information from the mandatory reporting. Of the
      first 1301 new HIV diagnoses reported in 2003, 43% were in women, and overall,
      53% were in heterosexuals, of whom 47% were of sub-Saharan African origin. MSM
      accounted for 36% of male notifications. A dried blood spot was available for 64%
      of new HIV diagnoses. Evidence of recent infection was found for 38%, ranging
      from 22% in IDUs to 58% in MSM. Twenty-six percent of infections in sub-Saharan
      migrants were recent infections. HIV-1 accounted for 98% of all notifications:
      48% of these were non-B subtypes. The first results of the HIV notification
      system indicate that heterosexual transmission is the predominant mode of
      transmission and that persons originating from sub-Saharan Africa are
      particularly affected. Over half of infections shown to be recently acquired were
      in MSM; this may indicate an increased HIV incidence in this population.

PMID- 15507729
TI  - Travel associated legionnaires' disease in Europe: 2003.
AB  - Six hundred and thirty two cases of travel-associated legionnaires' disease with
      onset in 2003 were reported to the EWGLINET surveillance scheme by 24 countries.
      Eighty nine clusters were detected, 35 (39%) of which would not have been
      detected without the EWGLINET scheme. One hundred and seven accommodation sites
      were investigated and 22 sites were published on the EWGLI website. The
      proportion of cases diagnosed primarily by the urinary antigen test was 81.2%,
      and 48 positive cultures were obtained. Thirty eight deaths were reported to the
      EWGLINET scheme, giving a crude fatality rate of 6%. Countries are encouraged to
      inform the coordinating centre of cases that fall ill after travelling within
      their own country of residence ('internal travel'), and are also encouraged to
      obtain patient isolates for culture where at all possible.

PMID- 15507730
TI  - Perspectives for a European Centre for Disease Prevention and Control.

PMID- 15507731
TI  - The European Centre for Disease Prevention and Control.

PMID- 15507732
TI  - Three-periodic nets and tilings: minimal nets.
AB  - The 15 3-periodic minimal nets of Beukemann & Klee [Z. Kristallogr. (1992), 201,
      37-51] have been examined. Seven have collisions in barycentric coordinates and
      are self-entangled. The other eight have natural tilings. Five of these tilings
      are self-dual and the nets are the labyrinth nets of the P, G, D, H and CLP
      minimal surfaces of genus 3. Twelve ways have been found for subdividing a cube
      into smaller tiles without introducing new vertices. Duals of such tilings with
      one vertex in the primitive cell have nets that are one of the minimal nets.
      Minimal nets without collisions are uniform.

PMID- 15507733
TI  - Formation of X-ray shift fringes and a new method for determination of the
      difference sign of interplanar distances.
AB  - A detailed investigation of the conditions for the formation of X-ray shift
      fringes is carried out, aiming to apply these patterns to investigations of
      crystal imperfections. Expressions for the amplitudes and X-ray intensity
      distribution are obtained for a two-crystal interferometer, in which the
      interplanar distance between two reflecting planes, d, has a relative change
      Deltad/d approximately 10(-8) - 10(-5). It is theoretically proven and
      experimentally confirmed that the value of the period of interference bands
      essentially depends on the sign of Deltad.

PMID- 15507734
TI  - Refinement of the crystal structural parameters of the intermediate phase of h
      BaTiO3 using convergent-beam electron diffraction.
AB  - Crystal structural parameters (21 positional parameters and nine isotropic Debye
      Waller factors) of the intermediate phase of hexagonal barium titanate (h-BaTiO3)
      have been refined by a structure analysis method using convergent-beam electron
      diffraction (CBED); this method was developed by Tsuda & Tanaka [Acta Cryst.
      (1999), A55, 939-954]. In order to perform the analysis, a parallel computation
      using a computer cluster composed of 16 connected Pentium 4 PCs was introduced. A
      function of parallel computation has been implemented in our analysis software,
      MBFIT, with the aid of the Message Passing Interface (MPI). Parallel computation
      enabled the present refinement to be conducted using a [001] CBED pattern and a
      [010] CBED pattern simultaneously. Reliable errors for the refined structural
      parameters have been obtained from the analyses of four independent experimental
      data sets instead of using the errors obtained by the error-propagation rule of
      least-squares fitting. The parameters obtained have been found to agree well with
      those determined by a neutron Rietveld analysis.

PMID- 15507735
TI  - Interlacing of growth steps on crystal surfaces as a consequence of
      crystallographic symmetry.
AB  - During crystal growth, concentric steps of unit-layer thickness [= dhklu with the
      surface's hkl Miller indices corrected according to the selection rules for non
      primitive lattices] are often found to split into lower steps in a regular
      fashion [Frank (1951). Phil. Mag. 42, 1014-1021]. These 'interlaced' step
      patterns are introduced by a stacking of two or more growth layers, with
      different lateral anisotropy in step velocity within each unit layer. In this
      paper, a general relation between the symmetry of the crystal surface and the
      configuration of the concentric step patterns thereon is derived and is used to
      give theoretical shapes of spirals, growth hillocks and etch pits. It is shown
      that many of the interlaced patterns and their details are imposed by the
      presence of screw axes and/or glide planes perpendicular to the crystal surface.
      Finally, the results are compared with the patterns of unit-layer height and
      lower steps observed by optical and atomic force microscopy on crystals such as
      SiC, GaN, potash alum, garnet and NiSO4*6H2O.

PMID- 15507736
TI  - Coordinate transformations in modern crystallographic computing.
AB  - A review of 4 x 4-matrix notation and of tensor formalism focused on
      crystallographic applications is presented. A discussion of examples shows how
      this notation simplifies tasks encountered in crystallographic computing.

PMID- 15507737
TI  - Modeling of the nuclear parameters for H atoms in X-ray charge-density studies.
AB  - Extensive and precise X-ray diffraction data for xylitol have been used to test
      different approaches to estimate nuclear parameters for H atoms in charge-density
      studies. The parameters from a neutron diffraction study of the same compound
      were taken as a reference. The resulting static charge densities obtained for the
      different approaches based on a multipole model were subjected to a topological
      analysis. The comparative analysis led to the following results. The procedure of
      extending the X-H bond to match bond lengths from neutron diffraction studies
      provides the best agreement with the neutron positional parameters. An isotropic
      model for the atomic displacements of H atoms is highly unsatisfactory and leads
      to significant deviations for the properties of the bond critical points
      including those that only involve non-H atoms. Anisotropic displacement
      parameters for H atoms can be derived from the X-ray data that are in agreement
      with the values from the neutron study, and the resulting charge-density models
      are in good agreement with the reference model. The anisotropic displacement
      parameters for H atoms are derived from the X-ray data as a sum of the external
      (rigid-body) and internal vibrations. The external vibrations are obtained from a
      TLS analysis of the ADPs of the non-H atoms and the internal vibrations from
      analysis of neutron diffraction studies of related compounds. The results from
      the analysis of positional and thermal parameters were combined to devise a 'best
      anisotropic' model, which was employed for three other systems where X-ray and
      neutron data were available. The results from the topological analysis of these
      systems confirm the success of the 'best anisotropic' model in providing
      parameters for the H atoms that give charge densities in agreement with the
      reference models based on H-atom parameters derived from neutron diffraction.

PMID- 15507738
TI  - Precise analysis of the components of diffraction by cylindrical crystals.
AB  - A detailed quantitative analysis of the various Bragg and Laue components of the
      integrated reflection power ratio for cylindrical crystals, and the dependence of
      these components on the Bragg angle, thetaB, the reduced radius, tau0 =
      sigma0rho, and the ratio of absorption coefficient to diffraction cross section,
      mu/sigma0 = xi0, is presented. The result indicates that the percentage of Laue
      and Bragg components of the integrated reflection power ratio is larger than 50%
      when thetaB < or = 20 degrees and murho < or = 1, and when thetaB > or = 10
      degrees and murho > or = 5. The reflection power ratio profile for cylindrical
      crystals with large murho is also discussed.

PMID- 15507739
TI  - Effects of near-neighbor correlations on the diffuse scattering from a one
      dimensional paracrystal.
AB  - The one-dimensional paracrystal model is generalized by folding the lattice sites
      with objects whose scattering lengths or sizes and separation display a spatial
      correlation from cell to cell. A general theory to calculate the diffuse
      scattering and the scattering-length autocorrelation function is developed. The
      investigated models of coupling along the paracrystalline chain are the
      correlations between (i) the sizes of the scatterers, (ii) the sizes of
      scatterers and their separations, and (iii) the sizes of scatterers and the
      fluctuation of their separation distances. In the first case (i), the size of a
      scatterer is, on average, linked to that of its neighbors. As a result, a
      continuous transition from the total lack of size correlation (known as
      decoupling approximation or DA) to the scattering from monodisperse domains
      (local monodisperse approximation or LMA) is obtained. In the second case of
      correlation (ii), the mean interobject distance is assumed to depend on the
      respective sizes of nearest neighbors. Depending on the introduced correlation
      parameter, aggregation or hard-core-type effects can be accounted for.
      Surprisingly, in some cases, it is possible to find a peak in the scattering
      curve without any structure in the total interference function. The size
      separation correlations may also dramatically reduce the scattering intensity
      close to the origin compared to the completely uncorrelated case. The last model
      (iii) foresees a coupling between the sizes of neighboring objects and the
      variance of the separation between neighbors. Within this model, on average along
      the chain, the fluctuations of distances between scatterers become dependent on
      the respective sizes of neighbors, while the mean distance between objects
      remains constant.

PMID- 15507740
TI  - On the real crystal rhombododecahedra.
AB  - In this paper, all the real crystal rhombododecahedra (625 in total) are
      enumerated and characterized by facet symbols and symmetry point groups. All the
      dodecahedra (34 in total) are drawn. Nine combinatorially different types are
      found among the garnets from Mt Makzapakhk, Kola Peninsula.

PMID- 15507741
TI  - Three exit beams from a single (hkl) X-ray diffraction plane.
AB  - An unusual case of three diffracted beams from a single incoming monochromatic X
      ray beam and from the same Bragg plane is reported. Extremely asymmetric
      diffraction in a thin Si perfect crystal with a cleaved lateral face was
      experimentally studied. Two of the beams emerge grazing the front and back faces
      and the third beam emerges from the lateral face.

PMID- 15507742
TI  - Lattice imaging in low-angle and high-angle bright-field scanning transmission
      electron microscopy.
AB  - Atomic resolution low-angle bright-field (LABF) scanning transmission electron
      microscope (STEM) images and high-angle bright-field (HABF) STEM images of [011]
      orientated Si have been experimentally obtained together with high-angle annular
      dark-field (HAADF) STEM images. The contrast formation mechanisms of the LABF
      STEM and HABF STEM images are examined in comparison with HAADF STEM images. The
      HABF STEM images independent of defocus and thickness have spatial resolution
      comparable with HAADF STEM images, and are shown to be given as a simple
      convolution under the non-dispersion approximation of localized Bloch waves.

PMID- 15507743
TI  - High-q-resolution neutron scattering technique using triple-axis spectrometers.
AB  - A new technique is presented that gives a substantial increase in the wavevector
      q resolution of triple-axis spectrometers by matching the measurement wavevector
      q to the reflection taua of a perfect-crystal analyzer. A relative Bragg width of
      deltaq/Q approximately 10(-4) can be achieved with reasonable collimation
      settings. This technique is very useful in measuring small structural changes and
      line broadenings that cannot be accurately measured with conventional set-ups,
      while keeping all the strengths of a triple-axis spectrometer.

PMID- 15507744
TI  - Ab initio determination of incommensurately modulated structures by charge
      flipping in superspace.
AB  - The charge flipping algorithm proposed by Oszlanyi & Suto [Acta Cryst. (2004),
      A60, 134-141] for ab initio reconstruction of crystal structures is generalized
      towards superspace. Its efficiency is demonstrated by successful reconstruction
      of eight known incommensurately modulated structures from experimental data. The
      output of the charge flipping algorithm is an electron density with symmetry P1.
      The symmetry of the structure is recovered by locating the positions of symmetry
      operators and averaging the density over the symmetry-related pixels. The
      reconstruction of a modulated structure by the charge flipping algorithm and the
      accuracy of the result is demonstrated in detail on the modulated structure of
      tetraphenylphosphonium hexabromotellurate(IV) bis[dibromoselenate(I)].

PMID- 15507745
TI  - Zones and sublattices of integral lattices.
AB  - Methods are presented for an analysis of zones and sublattices of integral
      lattices, whose relevance is revealed by sharp peaks in the frequency
      distribution of hexagonal and tetragonal lattices, as a function of the axial
      ratio c/a. Starting from a few examples, zone symmetries, lattice-sublattice
      relations and integral scaling transformations are derived for hexagonal lattices
      with axial ratios radical3/2, radical3, radical2 and 1 (the isometric case) and
      for the related radical3 and radical2 tetragonal lattices. Sublattices and zones
      connected by linear rational transformations lead to rational equivalence classes
      of integral lattices. For properties like the axial ratio and the point-group
      symmetry (lattice holohedry), rational equivalence can be extended so that also
      metric tensors differing by an integral factor become equivalent. These two types
      of equivalence classes are determined for the lattices mentioned above.

PMID- 15507746
TI  - Molecular crystal global phase diagrams. I. Method of construction.
AB  - A method is described to produce global phase diagrams for single-component
      molecular crystals with separable internal and external modes. The phase diagrams
      present the equilibrium crystalline phase as a function of the coefficients of a
      general intermolecular potential based on rotational symmetry-adapted basis
      functions. It is assumed that phase transitions are driven by orientational
      ordering of molecules with a fixed time-averaged shape. The mean-field
      approximation is utilized and the process begins in a high-temperature disordered
      reference state, then spontaneous symmetry-breaking phase transitions and phase
      structure information at lower temperature are sought. The information is mapped
      onto phase diagrams using the intermolecular expansion coefficients as
      independent variables. This is illustrated by global phase diagrams for molecules
      having tetrahedral symmetry (e.g. carbon tetrachloride, adamantane and white
      phosphorus). Uses of global phase diagrams include crystal structure data mining,
      guidance for crystal design and enumeration of likely or missing polymorphic
      structures.

PMID- 15507747
TI  - Space-group scanning tables.
AB  - Owing to page limitations, in Volume E: Subperiodic Groups of International
      Tables for Crystallography not all scanning tables were explicitly given.
      Instead, auxiliary tables were given providing information from which to
      construct the additional tables. The tables have been constructed and are
      presented here.

PMID- 15507748
TI  - Response to the paper A comparison between experimental and theoretical
      aspherical-atom scattering factors for charge-density refinement of large
      molecules, by Pichon-Pesme, Jelsch, Guillot & Lecomte (2004).

PMID- 15507751
TI  - Contribution of peroxidases in host-defense, diseases and cellular functions.
AB  - Peroxidases figure prominently in biology and contribute significantly to cell
      biology, host defense against infection, and pathogenesis of several inflammatory
      diseases. These varied and diverse aspects of peroxidase biochemistry and its
      clinical implications will be the subjects of in-depth analysis at the 4th
      International peroxidase meeting held in Kyoto. Specific topics range from the
      molecular basis of peroxidase structure and function to the clinical consequences
      of autoantibodies generated against myeloperoxidase (MPO), the peroxidase present
      in circulating neutrophils. Consideration of novel aspects of peroxidase biology,
      both unanticipated biochemical properties of MPO and the potential role of MPO in
      the pathogenesis of inflammatory diseases such as atherosclerosis, will also be
      included. In addition to peroxidases, the newly expanded family of NADPH oxidases
      will be discussed. We hope that this collection of scientists who share a common
      interest in peroxidase biology but each possess expertise in distinctly different
      aspects of the subject will provide a setting for spirited discussion and a
      lively exchange of views to yield advances in understanding and to create new
      applications of those insights to benefit clinical medicine, agriculture and
      industry.

PMID- 15507752
TI  - Genetic studies on myeloperoxidase deficiency in Italy.
AB  - Hereditary myeloperoxidase (MPO) deficiency is the most common neutrophil
      biochemical defect characterized by the lack of peroxidase activity. In order to
      extend the epidemiological studies on hereditary MPO deficiency in Italy,
      approximately 40,000 individuals were analyzed and 7 partial and 8 total MPO
      deficient subjects were identified. The genetic characterization of the subjects
      showed the presence of 3 already-known mutations (c.752T>C, c.1705C>T and
      c.1566_1579del14) and 6 novel mutations: four missense mutations (c.995C>T,
      c.1112A>G, c.1715T>G and c.1927T>C), then a deletion of an adenine within exon 3
      (c.325delA) and a mutation within the 3' splice site of intron 11 (c.2031-2A>C).
      The novel missense mutations cause the substitution of residues the p.A332V,
      p.D371G, p.L572W and p.W643R, respectively, and can cause potential structural
      changes. The c.325delA deletion causes a shift of the reading frame with the
      occurrence of a premature stop codon within the pro-peptide. An eukaryotic
      expression system was set up to investigate how the c.2031-2A>C mutation alters
      the MPO pre-mRNA splicing. The activation of a cryptic 3' splice site located
      109nt upstream of the authentic 3' splice site was observed. The 109nt-insertion
      might cause the rapid degradation of the MPO mRNA or, alternatively, might lead
      to the generation of an abnormal MPO precursor lacking the enzymatic activity.

PMID- 15507753
TI  - Genomic variations in myeloperoxidase gene in the Japanese population.
AB  - Myeloperoxidase (MPO; EC 1.11.1.7) is a lysosomal hemeprotein that plays an
      important role in the host defense mechanism against microbial diseases. This
      neutrophil disorder, characterized by the lack of MPO, may result in a weakened
      defense activity. Complete MPO deficiency has been postulated to be to originate
      from genomic mutation. Recently, two Japanese patients were reported with MPO
      deficiency. Both had base substitutions in the exon 9 region of the MPO gene; a
      region in close proximity functionally important residue, His502. Genomic DNA
      from 387 Japanese individuals was examined to determine the prevalence of these
      recently discovered base substitutions. None of these DNA samples possessed the
      mutations found in the MPO deficient cases, though two synonymous and one non
      synonymous mutation were found. The frequency of mutation in the exon 9 coding
      region was estimated to be one heterozygote in 129, thus the homozygote of such
      mutations would be revealed one in 16,000 in the Japanese population.

PMID- 15507754
TI  - Biosynthesis and sorting of myeloperoxidase in hematopoietic cells.
AB  - The neutrophil granulocytes have a critical role in innate immunity through
      killing of phagocytized microorganisms, in which myeloperoxidase (MPO)
      participates. MPO is stored in cytoplasmic azurophil lysosome-like granules
      together with other antibiotic proteins and digestive enzymes. During passage in
      the secretory pathway pro-MPO is folded, subjected to oligosaccharide
      modification, and retrieval from constitutive secretion to become targeted to
      azurophil granules for final processing and storage. Propeptide-deleted MPO
      precursor was found not to be processed to mature MPO and not to be targeted for
      storage but instead degraded or secreted. This indicated that the propeptide of
      the MPO precursor was a prerequisite for the final processing and granule
      targeting of proMPO. When the MPO propeptide was expressed as a chimera with a
      normally secretory protein, the ER retention of the chimera was prolonged
      compared with that of the native protein. Thus, the propeptide of MPO precursor
      may also mediate the normally long ER-residence of proMPO. Both mature MPO and
      secreted proMPO contained complex oligosaccharide side chains indicating that
      proMPO and, thus, mature MPO has passed the medial Golgi stack where complex
      oligosaccharides are formed, and exited at TGN like other proteins targeted for
      azurophil granules.

PMID- 15507755
TI  - In vivo role of myeloperoxidase for the host defense.
AB  - Myeloperoxidase (MPO) is located within neutrophils capable of producing HOCl. To
      define the in vivo role of MPO, we have generated MPO-knockout (MPO-KO) mice. The
      mice without MPO developed normally. However, MPO-KO mice showed severely reduced
      cytotoxicity to various microorganisms such as Candida albicans, Aspergillus
      fumigatus, and Klebsiella pneumoniae, demonstrating that MPO-dependent oxidative
      system is important for host defense against fungi and bacteria, although the
      effect varies from species to species of pathogens. To compare the importance of
      MPO and NADPH-oxidase for host defense, MPO-KO and chronic granulomatous disease
      (CGD) mice were infected with different doses of C. albicans, and their infection
      severity was analyzed. CGD mice exhibited increased mortality and tissue fungal
      burden in a dose-dependent manner, whereas normal mice showed no symptoms.
      Interestingly, at the highest dose, the mortality of MPO-KO mice was comparable
      to CGD mice, but was the same as normal mice at the lowest dose. These results
      suggest that MPO and NADPH-oxidase are equally important for early host defense
      against a large inocula of Candida.

PMID- 15507756
TI  - The clinical features and pathology of vasculitis associated with anti
      myeloperoxidase autoantibodies.
AB  - Autoantibodies to myeloperoxidase (MPO) are associated with the autoimmune
      disease, systemic vasculitis, in humans. This results in severe inflammation and
      microscopic necrosis of multiple organs, especially the kidneys, leading to renal
      failure and death. The discovery of MPO autoantibodies has permitted the
      development of new diagnostic tests allowing earlier diagnosis and more effective
      therapy. Furthermore these antibodies are directly implicated in tissue injury by
      binding to MPO on the neutrophil cell membrane and stimulating neutrophil
      activation and degranulation. The causes for the breakdown in tolerance to MPO
      are not known although rare cases are drug-induced and remit on drug withdrawal.
      An understanding of the biology of MPO and its involvement in the pathogenesis of
      vasculitis is of importance in understanding the pathogenesis of vasculitis and
      the development of newer therapies.

PMID- 15507758
TI  - Neutrophil microbicidal activity: screening bacterial mutants for survival after
      phagocytosis using quantitative PCR.
AB  - When a constant gene replacement sequence is introduced into bacteria to produce
      mutants and the flanking chromosomal sequences are known, it is possible to use a
      quantitative polymerase chain reaction method (QPCR) to compare the concurrent
      survival of the different bacterial mutants under identical conditions. We
      describe Escherichia coli survival following neutrophil phagocytosis among three
      mutants deleted respectively for araB, dps or oxyR. Comparisons were made both by
      traditional and QPCR methods with similar results and indicate that the survival
      defect of an oxyR and oxyS mutant described previously can be attributed to the
      loss of oxyR alone. Deletion of dps, a prominent member of the regulon controlled
      by the oxyR gene product does not engender a survival defect. We suggest that
      QPCR analysis can readily compare the relative survival of 10 or more mutants
      concurrently. QPCR analysis would seem to be especially valuable when
      experimental conditions are subject to a high degree of sample to sample
      variability or when the stress producing system involves use of expensive or
      scarce resources like rare patient cells, cells from children, or the use of
      genetically modified animal hosts.

PMID- 15507757
TI  - Intravenous immunoglobulin (IVIg) therapy in MPO-ANCA related polyangiitis with
      rapidly progressive glomerulonephritis in Japan.
AB  - For 30 myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA) related
      rapidly progressive glomerulonephritis patients (male 17, female 13, average age
      of 68 +/- 11.8 years old), intravenous immunoglobulin (IVIg) (400 mg/kg/day) was
      administered for 5 consecutive days before or along with conventional
      immunosuppressive therapy in Japan. Twenty patients were treated with IVIg before
      the start or newly increase of conventional therapy and evaluated the independent
      effect of this therapy. In these patients, just after IVIg, significant decrease
      of CRP from 8.61 +/- 5.77 to 5.47 +/- 4.50 mg/dl (P < 0.001) was noted with
      improvement of elevated serum creatinine in 12 out of 19 patients (63%). In the
      analysis of the overall outcome of 30 patients, at 3 months after IVIg and
      following conventional therapy, no patients showed renal death except 4 for whom
      hemodialysis had been started before IVIg. At 6 months, renal survival rate were
      92% (newly renal death 2 out of 26) and 2 patients died due to cerebral bleeding
      (survival rate was 93%). No fatal infection was noted. IVIg might be the potent
      inducible therapy which can be promoted before the beginning of conventional
      immunosuppressant treatment for relatively aged and lower immunopotent MPO-ANCA
      patients in Japan.

PMID- 15507759
TI  - Contribution of myeloperoxidase in vasculitis development.
AB  - Infiltrated neutrophils is believed to contribute to the progression of
      vasculitis. In particular, myeloperoxidase (MPO)-specific antibodies against
      neutrophils, anti-neutrophil cytoplasmic antibodies (MPO-ANCA) is involved in the
      development of vasculitis microscopic polyangiitis etc. In Japan a higher
      percentage of MPO-ANCA than that in Europe has been reported In addition, we
      showed a correlation of MPO-ANCA epitopes of Kawasaki disease patients by 47%
      with that of mothers'. On the other hand, mice having CADS/CAWS-induced
      vasculitis is a good model for the analysis of the production of MPO-ANCA. We
      have clarified that MPO is a major antigen for MPO-ANCA production using MPO KO
      mice. We also investigated the role of activated neutrophils in nephritis renal
      lesions using SCG/Kj mice. In the phase of nephritis with low grade of
      proteinuria, the spontaneous release of MPO from peripheral neutrophils
      increased, indicating that neutrophils are activated and contribute to the
      development of active crescentic lesion in SCG/Kj mice.

PMID- 15507760
TI  - The role of myeloperoxidase in the pathogenesis of coronary artery disease.
AB  - A growing body of evidence continues to emerge implicating the role of
      myeloperoxidase (MPO) and its oxidant products in the promotion of atherogenesis.
      A major mechanism by which MPO impacts the arterial wall is through its
      modification of net cellular cholesterol flux. MPO promotes lipid peroxidation
      and conversion of LDL to an atherogenic form, where it is taken up by
      macrophages, a critical step in foam cell formation. Emerging evidence suggests
      that HDL can also be modified by MPO derived oxidants, resulting in an impairment
      of cholesterol efflux. In addition, modified HDL appears to be a strong predictor
      of clinical risk. These features highlight MPO and its products as potential
      predictive markers and targets in atheroprotection.

PMID- 15507761
TI  - Mechanisms of activation of NADPH oxidases.
AB  - The members of the NOX family of enzymes are expressed in a variety of tissues
      and serve a number of functions. There is a high level of conservation of primary
      protein sequence, as well as functional features, although specialized responses
      are beginning to emerge. In this context, our data demonstrate that the NOX1
      cytoplasmic domains interact efficiently with the cytoplasmic subunits of the
      phagocyte NADPH oxidase and identify the second cytoplasmic loop of NOX electron
      transporters as a crucial domain for enzyme function. Studies of cytosolic co
      factors showed that the C-terminal cytoplasmic domain of NOX1 was absolutely
      required for activation with NOXO1 and NOXA1 and that this activity required
      interaction of the putative NADPH-binding region of this domain with NOXA1.
      Finally, we have provided the first example of how alternative splicing of a NOX
      co-factor may be involved in the regulation of NADPH oxidase function.

PMID- 15507762
TI  - Molecular mechanism underlying activation of superoxide-producing NADPH oxidases:
      roles for their regulatory proteins.
AB  - The phagocyte NADPH oxidase is dormant in resting cells but becomes activated
      during phagocytosis to produce superoxide, a precursor of microbicidal oxidants,
      thereby playing a crucial role in host defence. The catalytic core of this enzyme
      comprises the two membranous subunits gp91phox/Nox2 and p22phox. The oxidase
      activation requires the small GTPase Rac and the SH3 domain-containing proteins
      p47phox and p67phox; they normally exist in the cytoplasm and translocate upon
      cell stimulation to the membrane. The translocation depends on a stimulus-induced
      conformational change of p47phox, which leads to the SH3 domain-mediated
      interaction with p22phox, a binding required for the gp91phox/Nox2-dependent
      superoxide production. Activation of Nox1, an oxidase that is likely involved in
      host defence at the colon, requires novel proteins homologous to p47phox and
      p67phox, designated Noxo1 and Noxa1, respectively. Noxo1 and Noxa1, both
      expressed abundantly in the colon, are capable of constitutively activating Nox1.
      The constitutive activation may be due to the property of Noxo1: in contrast with
      p47phox, Noxo1 seems to normally associate with p22phox, which is required for
      the Nox1 activation. We will also describe the mechanism underlying regulation of
      the third oxidase Nox3, which exits in fetal kidney and inner ears.

PMID- 15507763
TI  - Clinical evaluation of interferon-gamma treatment to chronic granulomatous
      disease patients with splice site mutations.
AB  - IFN-gamma dependent increase of superoxide production by neutrophils was observed
      in three patients with Chronic Granulomatous disease from one family. The
      patients have the gp91-phox defect due to a splicing abnormality derived from a
      silent mutation adjacent to the third intron of CYBB gene. Apparent differences
      of splicing pattern of CYBB gene transcripts in patients' neutrophils were
      detected between 1 and 25 days after administration of IFN-gamma. Furthermore,
      the transcript containing all missing exons could be detected in all specimens
      after the treatment. The changes of splicing pattern in the transcripts and
      prolonged effect on superoxide generating ability of patients' neutrophils
      indicate that IFN-gamma induced an ability to correct abnormal splicing of CYBB
      gene transcripts in progenitor cells at least in part.

PMID- 15507764
TI  - Progress toward effective gene therapy for chronic granulomatous disease.
AB  - Previous clinical studies of ex vivo gene therapy for chronic granulomatous
      disease (CGD) without marrow conditioning have resulting in transient correction
      of the oxidase defect in over 0.1% of circulation neutrophils. Use of improved
      RD114 envelope pseudotyped vectors capable of transducing >95% of CD34+ stem
      cells ex vivo, together with non-ablative marrow conditioning will be
      incorporated into the next generation of clinical trials of ex vivo gene therapy
      for CGD. These maneuvers might result in clinical benefit to CGD patients from
      gene therapy.

PMID- 15507765
TI  - Tissue distribution and putative physiological function of NOX family NADPH
      oxidases.
AB  - The NOX family of ROS-generating NADPH oxidases consists of 7 members: NOX1 to
      NOX5, DUOX1 and 2. NOX1 is predominantly found in the colon, where it possibly
      plays a role in the host defense. NOX2 is the phagocyte NADPH oxidase, a clearly
      established host defense enzyme. NOX3 is almost exclusively expressed in the
      inner ear, where it is involved in otoconia morphogenesis, but based on its
      localization might also play a role in the auditory system. NOX4, widely
      expressed in kidney, vascular cells, osteoclasts etc.; it might be a
      constitutively active enzyme, regulated on the level of gene expression but its
      precise physiological function remains unknown. NOX5, a Ca2+ activated enzyme is
      predominantly expressed in lymphoid tissues and testis, where it might be
      involved in signaling processes. DUOX1 is expressed in the thyroid and in
      respiratory epithelia, and DUOX2 in the thyroid and in gastrointestinal glandular
      epithelia. Both DUOX enzymes are involved in thyroid hormone synthesis, but
      possibly also in epithelial host defense.

PMID- 15507766
TI  - Kinetics of interconversion of redox intermediates of lactoperoxidase, eosinophil
      peroxidase and myeloperoxidase.
AB  - Myeloperoxidase, eosinophil peroxidase and lactoperoxidase are heme-containing
      oxidoreductases, which undergo a series of redox reactions. Though sharing
      functional and structural homology, reflecting their phylogenetic origin,
      differences are observed regarding their spectral features, substrate
      specificities, redox properties and kinetics of interconversion of the relevant
      redox intermediates ferric and ferrous peroxidase, compound I, compound II and
      compound III. Depending on substrate availability, these heme enzymes path
      through the halogenation cycle and/or the peroxidase cycle and/or act as poor
      (pseudo-) catalases.

PMID- 15507767
TI  - Reactions of superoxide with myeloperoxidase and its products.
AB  - Myeloperoxidase (MPO) uses hydrogen peroxide to oxidize chloride to hypochlorous
      acid. It also converts numerous substrates to reactive free radicals. When
      released by neutrophils, the enzyme operates in the presence of a flux of
      superoxide. We show that superoxide has a profound influence on oxidative
      reactions catalysed by MPO. It reacts directly with the enzyme to modulate
      production of hypochlorous acid. Within neutrophil phagosomes, where MPO
      functions to kill micro-organisms, it may be the preferred substrate for the
      enzyme. Superoxide also reacts rapidly with radicals generated by MPO, e.g. from
      tyrosine and tyrosyl peptides. Initial products are organic peroxides. These
      species are likely to be toxic and contribute to the pathophysiological actions
      of MPO.

PMID- 15507768
TI  - Reactions of 1-methyl-2-mercaptoimidazole with hypochlorous acid and superoxide.
AB  - Reactions of thioureylene antithyroid drugs (1-methyl-2-mercaptoimidazole and
      carbimazole) with hypochlorous acid (HOCl) and superoxide were followed optically
      and products were analyzed by mass spectrometry. 1-methyl-2-mercaptoimidazole
      (MMI) and carbimazole reacted rapidly with HOCl with a rate constant of 1 x 10(7)
      and 7 x 10(6) M(-1)s(-1), respectively. The characteristic spectrum assigned to
      MMI disulfide appeared immediately after addition of HOCl, followed by a slow
      conversion to a final spectrum. The conversion was dependent upon the ratio of
      HOCl to MMI and both antithyroid drugs uptake 3 moles HOCl for complete
      conversion. A similar sequence of spectral changes was also observed when the
      HOCl was replaced by myeloperoxidase (MPO)/H2O2/Cl- system. The final oxidation
      product of MMI and carbimazole with HOCl and superoxide was 1-methylimidazole.

PMID- 15507769
TI  - Lessons from MPO deficiency about functionally important structural features.
AB  - Genetic abnormalities often serve as the catalyst to stimulate critical insights
      into normal biology. In many cases, examining such experiments of Nature
      explicates not only the abnormal but also serves to illustrate underlying normal
      principles. Within the context of myeloperoxidase biosynthesis, we have examined
      the impact of specific missense mutations that cause inherited myeloperoxidase
      deficiency. Such studies have provided novel insights not otherwise possible. We
      have described three such mutations and are completing the analysis of a fourth.

PMID- 15507770
TI  - The influence of autoantibodies to myeloperoxidase on neutrophil function and
      intracellular signaling.
AB  - Autoantibodies to myeloperoxidase (MPO) are associated with small vessel systemic
      vasculitis. Interactions of these autoantibodies with MPO target antigen, Fcgamma
      receptors and Beta2 integrins at the neutrophil surface, can set in train a
      sequence of intracellular signal transduction events that culminate with
      functional responses. These include a respiratory burst with release of
      superoxide ions, degranulation, cytokine release, enhanced adhesion and induction
      of an accelerated apoptotic program.

PMID- 15507771
TI  - Newer insights into the aetiology and pathogenesis of myeloperoxidase associated
      autoimmunity.
AB  - In recent years there have been substantial developments in the understanding of
      the aetiology and pathogenesis of ANCA-associated vasculitides, including
      myeloperoxidase (MPO) associated autoimmunity. This review will describe genetic
      and environmental factors that may increase the risk for the disease and will
      summarise findings demonstrating that T-cells, B-cells and ANCA themselves are of
      pathogenetic significance. Leukocyte gene expression profiles indicate that the
      reactivation of granule protein genes contributes to the pathogenesis of AASV.
      Finally, data derived from closely related autoantibodies against proteinase 3
      (PR3) suggest anti-idiotypic antibodies induced by antisense transcripts as
      potential pathological agents.

PMID- 15507772
TI  - Murine model of Kawasaki disease induced by mannoprotein-beta-glucan complex,
      CAWS, obtained from Candida albicans.
AB  - Intraperitoneal administration of CAWS (water-soluble extracellular
      polysaccharide fraction obtained from the culture supernatant of Candida
      albicans) to mice induces coronary arteritis similar to Kawasaki disease. We
      analyzed differences in the production of cytokines involved in the occurrence of
      coronary arteritis among mouse strains, C3H/HeN, C57BL/6, DBA/2 and CBA/J. The
      incidence of arteritis was 100% in C57BL/6, C3H/HeN and DBA/2 mice, but only 10%
      in CBA/J mice. The coronary arteritis observed in DBA/2 mice was the most
      serious, with several mice expiring during the observation period. The CAWS
      sensitive strains revealed increased levels of IL-6 and IFN-gamma during the
      course of a specific response to CAWS by spleen cells. In contrast, IL-10 levels
      were observed to increase markedly in CAWS-resistant CBA/J mice, but not the CAWS
      sensitive strains. However, TNF-alpha levels were more elevated only in DBA/2
      mice. The difference in disease development and cytokine production strongly
      suggests that the genetic background of the immune response to CAWS contributes
      to the occurrence of coronary arteritis.

PMID- 15507773
TI  - A nosocomial outbreak of febrile bloodstream infection caused by heparinized
      saline contaminated with Serratia marcescens, Tokyo, 2002.
AB  - In January 2002, 12 patients with Serratia marcescens bloodstream infection (BSI)
      were identified in a hospital in Tokyo, Japan. We conducted an epidemiological
      investigation of this outbreak. We undertook a medical-records review and
      employee interviews, and performed a case-control study to determine risk factors
      for S. marcescens BSI. An observational study of the hospital's procedures and an
      environmental microbiologic sampling were performed. We identified 12 suspected
      and 12 confirmed patients with S. marcescens BSI, including 7 who died. A case
      control study showed that vascular access devices (odds ratio [OR] = 30.46; 95%
      confidence interval [CI] = 3.5-685.6) and the use of heparin-locks, between
      December 26 and January 15 (OR = 25.7; 95% CI = 2.3-680.4) were significant risk
      factors for S. marcescens BSI. The observational study revealed multiple lapses
      in infection control, including use of multi-dose vials of heparin. The outbreak
      strain was isolated from a hand-towel in the nurse station. The use of multi-dose
      vials of heparinized-saline during a particularly busy period was associated with
      BSI risk. The results underscore the risks inherent in infection-control lapses
      and the use of multi-dose vials.

PMID- 15507774
TI  - Human leptospirosis in Erode, South India: serology, isolation, and
      characterization of the isolates by randomly amplified polymorphic DNA (RAPD)
      fingerprinting.
AB  - The study describes the first attempt to record leptospirosis in Erode by
      isolation and serological tests such as the microscopic agglutination test and
      IgM-based enzyme-linked immunosorbent assay. Twenty-nine clinically suspected
      cases showing fever, headache, body ache associated with jaundice, decreased
      urine output, and conjunctival suffusion were included. The age of the patients
      ranged between 10-71 years and most of them were agricultural workers. Paired
      sera were possible among 12 cases. All the patients had fever and headache and
      other more common symptoms were myalgia and icterus. Leptospiral culture was
      positive in 7 (24.1%) patients. Out of 29 patients, 26 (89.7%) were diagnosed as
      having current leptospiral infection based on serology and isolation. The
      leptospiral isolates KSR 1-6 were further characterized by using randomly
      amplified polymorphic DNA fingerprinting shown genetic similarities with
      Leptospira interrogans spp. This study shows the presence of leptospirosis among
      the hospital cases of Erode and that this disease is a potential health hazard of
      agricultural workers in Cauvery basin.

PMID- 15507775
TI  - Rifampicin antagonizes the effect of choloroquine on chloroquine-resistant
      Plasmodium berghei in mice.
AB  - Chloroquine (CQ)-resistant Plasmodium falciparum appears to decrease CQ
      accumulation in its food vacuole by enhancing its efflux via an active membrane
      pump, which has been reported to be a P-glycoprotein-like transporter. Rifampicin
      (RIF) is a P-glycoprotein inhibitor and also has some antimalarial activity. It
      is hoped that a combination of choloroquine-rifampicin (CQ + RIF) would be
      advantageous in the treatment of CQ-resistant malaria. Swiss albino mice were
      inoculated with CQ-resistant P. berghei intraperitoneally, and studied for the
      effect of CQ versus the combination of CQ + RIF at various doses on the clearance
      of parasitemia, the survival of the mice, and the recrudescence of malaria.
      Paradoxically, RIF decreased the survival rate and rate of clearance of
      parasitemia and increased the rate of recrudescence significantly when combined
      with various doses of CQ. Our results indicated that RIF worsened the course of
      the disease, and we concluded that RIF should not be combined with CQ in the
      treatment of malaria.

PMID- 15507776
TI  - Cryptococcuria as a manifestation of disseminated cryptococcosis and isolated
      urinary tract infection.
AB  - Fungal infection of the genitourinary system is a relatively uncommon
      presentation. Cryptococcuria has rarely been recognized in clinical practice.
      Patients with positive urine culture for Cryptococcus neoformans from 1992 to
      2003 were retrospectively reviewed. Sixteen patients were identified. Nine (56%)
      patients were male, with a mean age of 44 +/- 21 (range, 16-88) years. Fifteen
      (94%) patients had underlying conditions such as HIV infection, diabetes
      mellitus, hypertension, and/or systemic lupus erythematosus. Thirteen (81%)
      patients had cryptococcuria as a manifestation of disseminated cryptococcosis,
      and the rest had only isolated cryptococcuria. Urinary analysis revealed
      proteinuria (75%), pyuria (31%), and budding yeast (13%). Nine (56%) patients
      received antifungal therapy. Other patients were misdiagnosed or died before
      treatment. The mortality rate was 64%. In conclusion, cryptococcuria is not
      extremely rare and can present as a manifestation of disseminated cryptococcosis
      or isolated urinary tract infection.

PMID- 15507777
TI  - Pulsed-field gel electrophoresis of multidrug-resistant and -sensitive strains of
      Pseudomonas aeruginosa from a Malaysian hospital.
AB  - Over a period of 6 months from January to June 2002, an unusual increase in the
      isolation of highly resistant Pseudomonas aeruginosa strains was observed in the
      various wards and intensive care units of a large general hospital in Johor
      Bahru, Malaysia. An equal number of multidrug resistant (MDR) and drug
      susceptible strains were collected randomly from swabs, respiratory specimens,
      urine, blood, cerebral spinal fluid, and central venous catheters to determine
      the clonality and genetic variation of the strains. Macrorestriction analysis by
      pulsed-field gel electrophoresis showed that the 19 MDR strains were genetically
      very homogenous; the majority showed the dominant profile S1 (n = 10), the rest
      very closely related profiles S1a (n = 1), S2 (n = 4), and S2a (n = 3),
      indicating the endemicity of these strains. In contrast, the 19 drug-sensitive
      strains isolated during the same time period were genetically more diverse,
      showing 17 pulsed-field profiles (F = 0.50-1.00), and probably derived from the
      patients themselves. The presence of the MDR clone poses serious therapeutic
      problems as it may become endemic in the hospital and give rise to future clonal
      outbreaks. There is also the potential for wider geographical spread.

PMID- 15507778
TI  - Long-term post-Salmonella reactive arthritis due to Salmonella Blockley.
AB  - We describe the case of a patient who became ill with Salmonella Blockley food
      poisoning while working in Cyprus in August 1994. As his diarrhoea resolved he
      began to suffer from lower limb joint pains which were diagnosed as acute
      salmonella reactive arthritis. His condition deteriorated, then improved somewhat
      over a period of 2 years, but he continued to suffer symptoms over 5 years after
      infection. This case predates other reported cases of S. Blockley infection in
      Cyprus by 4 years. S. Blockley is associated with chickens, and the chicken meal
      is the probable source of his infection. This case is of interest since it
      demonstrates the emergence of the serovar outside South East Asia where it is
      common, and shows that information on the incidence and duration of reactive
      arthritis caused by serovars other than S. Enteritidis and S. Typhimurium is
      limited.

PMID- 15507779
TI  - Severe leukopenia associated with mild hepatotoxicity in an HIV carrier treated
      with nevirapine.
AB  - Nevirapine is a non-nucleoside reverse transcriptase inhibitor used in the
      treatment of human immunodeficiency virus (HIV)-infected patients and in post
      exposure prophylaxis. However, its use has recently been limited because of
      adverse cutaneous and hepatic effects. We report an HIV-infected woman who
      developed mild leukopenia as the first sign of a nevirapine-related adverse
      event, which was followed by skin and hepatic toxicity associated with a more
      severe leukopenia.

PMID- 15507780
TI  - An adult case of Chryseobacterium meningosepticum meningitis.
AB  - Chryseobacterium meningosepticum is an uncommon pathogen causing adult bacterial
      meningitis. Herein, we report the case history of one 21-year-old woman with this
      uncommon central nervous system infection. A diagnosis of adult C.
      meningosepticum meningitis can only be confirmed by a positive cerebrospinal
      fluid (CSF) culture. The patient had insulin-dependent diabetes mellitus as the
      underlying condition associated with this infection. The clinical presentations
      were fever, headache, consciousness disturbance, and seizure. CSF analysis
      revealed a purulent inflammatory reaction. After a 21-day course of intravenous
      cefepime (6 g/day) treatment, this patient was discharged in a state of complete
      recovery.

PMID- 15507781
TI  - Cryptosporidium Spp., a frequent cause of diarrhea among children at the Korle-Bu
      Teaching Hospital, Accra, Ghana.
AB  - This report presents the results of a study conducted at the Child Health
      Department, Korle-Bu Teaching Hospital, Accra, Ghana, between the months of
      October 2001 and June 2002. Stool samples from 227 children with diarrhea and 77
      children without diarrhea, aged less than 5 years, were tested for
      Cryptosporidium spp. Prevalence rates were 27.8 and 15.6% in children with and
      without diarrhea, respectively. Cryptosporidium infection was found to be high in
      children between the ages of 6 and 24 months. Cryptosporidium spp. was more
      common in malnourished children, but was not isolated in children under 6 months
      of age who were exclusively breastfed. Neither the presence of domestic animals,
      abdominal pain, blood in stool, nausea, vomiting, nor the consumption of
      untreated water was associated with Cryptosporidium spp. infection. Shigella,
      Salmonella, and yeast-like organisms were the most frequently identified
      enteropathogenic bacteria. In summary, this study demonstrates the prevalence of
      Cryptosporidium spp. among Ghanaian children.

PMID- 15507782
TI  - Stimulation of virus-specific T cell responses by dendritic cell vaccination in
      the chronic phase of simian AIDS models.
AB  - Virus-specific CD8+ cytotoxic T lymphocyte (CTL) responses play an important role
      in the control of immunodeficiency virus infections. Therapeutic immunization
      with antigen-pulsed dendritic cells (DC) may be a promising strategy for
      stimulating CTL. However, decreases in DC number and function have been suggested
      in the host persistently infected with the virus, and this may constitute an
      obstacle to DC-based immunotherapy in the chronic phase. In this study, we show
      that virus-specific CTL responses were augmented by therapeutic immunization with
      inactivated virus-pulsed autologous DC in rhesus macaques that had maintained
      prophylactic vaccine-based control of virus replication for more than 3 years
      after simian or simian-human immunodeficiency virus challenge. Our results
      indicate the potential of DC in the chronic phase for efficiently stimulating CTL
      in vivo, suggesting the feasibility of therapeutic DC immunization for
      replenishing virus-specific CTL responses in the chronic phase after the
      prophylactic vaccine-based control of primary immunodeficiency virus infection.

PMID- 15507783
TI  - Seroprevalence of anti-flagellin antibody against Burkholderia pseudomallei in
      Taiwan.

PMID- 15507784
TI  - Molecular epidemiology of methicillin-resistant Staphylococcus aureus,
      Pseudomonas aeruginosa and Serratia marcescens in a long-term care facility for
      patients with severe motor and intellectual disabilities.

PMID- 15507785
TI  - Introduction to the consensus recommendations.

PMID- 15507786
TI  - Consensus recommendations on the use of botulinum toxin type a in facial
      aesthetics.
AB  - The use of botulinum toxin type A for facial enhancement is the most common
      cosmetic procedure currently undertaken in the United States. Overall clinical
      and study experience with botulinum toxin type A treatment for facial enhancement
      has confirmed that it is effective and safe in both the short and long term.
      Nevertheless, consistent guidelines representing the consensus of experts for
      aesthetic treatments of areas other than glabellar lines have not been published.
      Therefore, a panel of experts on the aesthetic uses of Botox Cosmetic (botulinum
      toxin type A; Allergan, Inc., Irvine, Calif.) was convened to develop consensus
      guidelines. This publication comprises the recommendations of this panel and
      provides guidelines on general issues, such as the importance of the aesthetic
      evaluation and individualization of treatment, reconstitution and handling of the
      botulinum toxin type A, procedural considerations, dosing and injection-site
      variables, and patient selection and counseling. In addition, specific
      considerations and recommendations are provided by treatment area, including
      glabellar lines, horizontal forehead lines, "crow's feet," "bunny lines"
      (downward radiating lines on the sides of nose), the perioral area, the dimpled
      chin, and platysmal bands. The review of each area encompasses the relevant
      anatomy, specifics on injection locations and techniques, starting doses (total
      and per injection point), the influence of other variables, such as gender, and
      assessment and retreatment issues. Factors unique to each area are presented, and
      the discussion of each treatment area concludes with a review of key elements
      that can increase the likelihood of a successful outcome. Summary tables are
      provided throughout.

PMID- 15507787
TI  - Cervical muscle response to whiplash-type right lateral impacts.
AB  - STUDY DESIGN: Nine healthy volunteers were subjected to right lateral impacts of
      4.9, 8.8, 10.8, and 13.7 m/sec acceleration at two levels of expectation:
      expected and unexpected. OBJECTIVES: To determine the response of the cervical
      muscles to increasing low-velocity right lateral impacts and compare the
      quantitative effects of expected and unexpected impact. SUMMARY OF BACKGROUND
      DATA: The literature contains little information on the etiology of whiplash
      injuries. In particular, in vivo studies of the cervical muscular response and
      head-neck kinematics to lateral impacts are rare. A previous study of left
      lateral impacts suggests that the burden of impact is borne primarily by the
      muscles contralateral to the side of impact. METHODS: Bilateral electromyograms
      of the sternocleidomastoids, trapezii, and splenii capitis were recorded.
      Triaxial accelerometers recorded the acceleration of the chair, torso at the
      shoulder level, and head of the participant. RESULTS: At an acceleration of 13.7
      m/sec2, both sternocleidomastoids, both trapezii, and the right splenius capitis
      generated on average around 40% or less of their maximal voluntary contraction
      electromyogram in both the expected and unexpected impact conditions. The left
      splenius capitis (i.e., contralateral to the right lateral impact), however,
      generated 84% of its maximal voluntary contraction electromyogram (double the
      response of other muscles). Electromyographic variables were affected
      significantly by the levels of acceleration (P < 0.01). The time to onset and
      time to peak electromyogram time for all muscles decreased progressively with
      increasing levels of acceleration. The kinetic variables and the
      electromyographic variables regressed significantly on the acceleration (P <
      0.01), and the head acceleration was affected significantly by expectation (P <
      0.01). In response to right lateral impacts, muscle responses were generally
      greater, with higher levels of acceleration, and greatest for the splenius
      capitis muscle contralateral to the side of impact (P < 0.01). CONCLUSIONS:
      Because the muscular component of the head-neck complex likely plays a central
      role in the abatement of higher acceleration levels, it may be a primary site of
      injury in the whiplash phenomenon in lateral collisions, and specifically, the
      splenius capitis muscle contralateral to the side of impact is most likely to be
      injured. Being aware of an impact may reduce the degree of head perturbation.

PMID- 15507788
TI  - Surgical treatment for atlantoaxial subluxation with myelopathy in
      spondyloepiphyseal dysplasia congenita.
AB  - STUDY DESIGN: A retrospective review of 21 patients with spondyloepiphyseal
      dysplasia congenita (SEDC), including 7 operated patients for atlantoaxial
      subluxation. OBJECTIVES: To clarify the morphological findings of atlantoaxial
      subluxation in SEDC patients and to evaluate the operative procedures based on
      these image findings. SUMMARY AND BACKGROUND DATA: The presence of atlanto axial
      sublucation with hypoplasia of the odontoid and/or lax ligaments leads to
      myelopathy in patients with spondyloepiphyseal dysplasia congenita. METHODS: We
      retropectively reviewed the physical and morphological findings on atlantoaxial
      images and the clinical findings of myelopathy in 21 patients with SEDC. RESULTS:
      Myelopathy was found in 9 individuals with severe SEDC who presented with marked
      short stature and severe coxa vara; of these, 6 had gait disturbances. On the
      images of the 9 patients with myelopathy, the average sagittal canal diameter
      (SCD) at the level of the atlas was only 9.2 mm (range, 7-12 mm) with progressive
      atlantoaxial subluxation. The average atlantodental interval (ADI) was 3.5 mm
      (range, 2-6 mm) in the presence of a sagittal atlas diameter (SAD) of less than
      27.1 mm (range, 22-36 mm). Surgery was performed for 6 of the patients with
      myelopathy. Since their SADs were small, and the average SCD, at 9.9 mm (8-14
      mm), was narrow even at the position of extension (the position of reduction for
      atlantoaxial subluxation), C1 laminectomy was needed for all these patients, and
      occipital-cervical posterior fusion was performed. Stability was satisfactory in
      all cases and the operative outcome for myelopathy was excellent for 1 case, fine
      for 4, and fair for 2. CONCLUSION: A small SAD may limit the effectiveness of
      reducing atlantoaxial subluxation. Persistent narrowing of the SCD may require
      concomitant C1 laminectomy and occipital-cervical fusion.

PMID- 15507789
TI  - Concurrent comparison of responsiveness in pain and functional status
      measurements used for patients with low back pain.
AB  - STUDY DESIGN: Prospective study of two samples of patients with acute and chronic
      low back pain, respectively. OBJECTIVES: To compare the responsiveness of four
      functional status questionnaires, Roland Morris Disability Questionnaire (RMDQ),
      Oswestry Disability Index (ODI), Disability Rating Index (DRI), and Physical
      Functioning scale of the SF-36 (PFSF-36), and two pain scales, a Numerical Pain
      Rating Scale (NRS) and Visual Analogue Scale (VAS). SUMMARY OF BACKGROUND DATA:
      Concurrent comparisons of different outcome measurements in back patients have
      been requested. METHODS: Norwegian versions of the scales and questionnaires were
      completed by 54 patients with acute (<3 weeks) and 50 patients with chronic low
      back pain (>3 months). Clinical change was estimated on a global change index. An
      alternative external criterion was the expected clinical course in the two
      cohorts. Mean changes, standardized response mean (SRM), and area under the
      receiver operating characteristic (ROC) curves with cutoff point for highest
      sensitivity and specificity were calculated. RESULTS: At the follow-up, 63% of
      the acute and 41% of the chronic sample reported improvement on the global change
      index. Large SRMs (1.3-2.0) and areas under the ROC curves (0.84-0.93) were found
      for the measurements in the acute sample. In the chronic sample, the SRMs (0.4
      1.1) and areas under the ROC curves (0.65-0.83) were lower, in particular for the
      PFSF-36 and the VAS. There was no statistically significant difference between
      the responsiveness in the measurements, except for higher responsiveness in the
      NRS compared with the VAS when using expected clinical course as the external
      criterion for change. CONCLUSION: The results suggest that all the outcome
      measures were appropriate for measuring changes in functional status and pain in
      patients with acute low back pain, whereas among chronic patients the RMDQ, ODI,
      DRI, and NRS were most appropriate.

PMID- 15507790
TI  - Spontaneous hemorrhage of a spinal ependymoma: a rare cause of acute cauda equina
      syndrome: a case report.
AB  - STUDY DESIGN: An interesting case of spontaneous bleeding from an ependymoma of
      the filum terminale is presented. OBJECTIVES: To document a rare case of rapid
      neurologic deterioration as a consequence of spinal tumoral hemorrhage and to
      highlight important issues regarding tumor histologic subtype and the impact of
      anticoagulation that have emerged from an illuminating review of the literature.
      SUMMARY OF BACKGROUND DATA: To our knowledge, there have been only 8 reported
      cases of hemorrhage from an ependymoma of the filum terminale or conus medullaris
      causing acute cauda equina syndrome. Bleeding is described in the pathology texts
      as being a consequence of the vascular architecture of the myxopapillary subtype
      and so postulated to be more common in this group. Anticoagulation is recognized
      to increase the frequency of tumoral bleeding, but no studies report its effect
      of severity of clinical presentation. METHODS: We report the case of a 57-year
      old woman who developed nontraumatic acute cauda equina syndrome, including
      sphincter compromise. She underwent a lumbosacral laminectomy for evacuation of a
      hematoma, at which stage a filum terminale ependymoma was excised.
      Histopathologic analysis demonstrated it to be of a nonmyxopapillary subtype.
      RESULTS: The patient demonstrated gradual improvement of the neurologic deficit.
      At 12-month follow-up, her saddle area sensory deficit has resolved, her right
      lower limb is much stronger allowing her to walk long distances, and she is
      successfully performing intermittent self-catheterization of her bladder.
      CONCLUSIONS: The possibility of an underlying tumor should always be borne in
      mind so that adequate preoperative planning can be undertaken. The presence of
      the myxopapillary subtype should not prevent a clinician from excluding other
      reasons for hemorrhage, and counseling when reinstituting anticoagulation must
      include warning against a worse prognosis from any future hemorrhage.

PMID- 15507791
TI  - Radiotherapy-induced malignant peripheral nerve sheath tumor of the cauda equina.
AB  - STUDY DESIGN: Case report. OBJECTIVES: To report a rare case of radiation-induced
      malignant peripheral nerve sheath tumor of the cauda equina 10 years after
      treatment for testicular seminoma. SUMMARY OF BACKGROUND DATA: Development of
      malignant peripheral nerve sheath tumor after irradiation is well recognized and
      often associated with a dismal prognosis. There have been isolated reports of
      malignant peripheral nerve sheath tumor developing in sites of previous
      irradiation for testicular seminoma. METHODS: Retrospective review of case
      records and imaging. RESULTS: A 38-year-old man presented with signs of cauda
      equina syndrome. Ten years previously, he had undergone right radical inguinal
      orchidectomy and adjuvant para-aortic radiotherapy as treatment for Stage I
      testicular seminoma. Magnetic resonance imaging demonstrated an inoperable intra-
      and extradural tumor leading to significant cauda equina compression. CT-guided
      biopsy revealed a diagnosis of malignant peripheral nerve sheath tumor, most
      likely due to previous radiotherapy. His clinical condition did not improve, and
      he underwent a course of palliative chemotherapy. CONCLUSIONS: Postirradiation
      malignant peripheral nerve sheath tumors are rare and occur in a population at
      high risk of developing second malignancies. The authors report the fourth case
      resulting from adjuvant radiotherapy for testicular seminoma, with the present
      report being the first report of extensive intradural tumor leading to cauda
      equina syndrome.

PMID- 15507793
TI  - Effectiveness of salmon calcitonin nasal spray in the treatment of lumbar canal
      stenosis: a double-blind, randomized, placebo-controlled, parallel group trial.
AB  - STUDY DESIGN: Double-blind, randomized, placebo-controlled study to assess the
      effectiveness of calcitonin nasal spray on symptoms and function in patients with
      lumbar canal stenosis. OBJECTIVE: To compare effectiveness of calcitonin
      administered by nasal spray with placebo in patients with clinically symptomatic
      lumbar canal stenosis. SUMMARY OF BACKGROUND DATA: Lumbar canal stenosis is the
      most common reason for spine surgery in individuals over 65 years of age.
      Nonoperative approaches have been not well studied and limited primarily to
      physical therapy exercises. Several small trials in the past have suggested that
      subcutaneous and intramuscular calcitonin is an effective nonsurgical option in
      treating the symptoms of spinal stenosis patients. Only three trials were
      randomized and placebo-controlled. METHODS: Fifty-five patients with clinical
      lumbar canal stenosis (pseudoclaudication), confirmatory MR imaging, and pain
      intensity index (VAS) of > or =6 were randomized to either placebo or intranasal
      calcitonin daily for 6 weeks, followed by an open label 6-week extension, during
      which all patients received active drug. Outcome parameters performed at
      baseline, 6 weeks, and 12 weeks, included pain intensity index, walking time and
      distance to pain, SF-36, and Oswestry disability index. RESULTS: Thirty-six
      patients received calcitonin, and 19 placebo. Eight (14.54%) calcitonin and 4
      (7.27%) placebo patients withdrew from the study. The mean baseline pain score
      for calcitonin group was 7.8 and 7.5 for placebo. Comparisons at week 6 showed no
      statistically significant difference in the change in pain intensity (VAS)
      between calcitonin group (-2.9) and placebo (-2.4) (P = 0.4382) from baseline.
      There was no significant difference in walking time to pain (calcitonin -10.0
      seconds; placebo +32.2 seconds; P = 0.5136). Walking distance to pain showed a
      mean improvement of +91.4 ft in the calcitonin group and +254.7 ft in the placebo
      group (P = 0.4948). No significant difference was observed in the SF-36 score
      between the treatment groups. Using a threshold of at least 50% reduction in pain
      from baseline to 6 weeks, 12 of 29 (41.37%) of calcitonin patients were
      considered responders versus 7 of 18 (38.88%) of placebo patients (P = 0.4238)
      CONCLUSIONS: In this first ever largest randomized placebo-controlled parallel
      group trial of nasal calcitonin in spinal stenosis, nasal calcitonin was not
      superior to placebo in treating the symptoms of spinal stenosis at 6 weeks. Based
      on this study, nasal calcitonin does not appear to have a role in nonoperative
      treatment of lumbar canal stenosis.

PMID- 15507794
TI  - Early intervention for the management of acute low back pain: a single-blind
      randomized controlled trial of biopsychosocial education, manual therapy, and
      exercise.
AB  - STUDY DESIGN: A single blind randomized controlled trial comparing two models of
      care for patients with acute simple low back pain. OBJECTIVES: To compare two
      research-based models of care for acute low back pain and investigate the effect
      of the timing of physical intervention. SUMMARY OF BACKGROUND DATA: National
      guidelines offer conflicting information on the delivery of physical treatment in
      the management of acute low back pain. The guidelines suggest two different
      models of care. Direct comparisons between these models are lacking in the
      literature. The present study aims to compare these approaches to the management
      of acute low back pain. METHODS: Among 804 referred patients, 102 subjects met
      the specific admission criteria and were randomly assigned to an
      "assess/advise/treat" group or an "assess/advise/wait" group. The intervention
      consisted of biopsychosocial education, manual therapy, and exercise. Assessment
      of short-term outcome enables comparison to be made between intervention and
      advice to stay active. Assessment of long-term outcome enables comparison to be
      made between early and late intervention. Study outcomes of reported pain (Visual
      Analogue Scale), functional disability (the Roland and Morris Disability
      Questionnaire), mood (Modified Zung Self Rated Depression Score, Modified Somatic
      Perception Questionnaire, State-Trait Anxiety Inventory), general health
      (Euroqol), and quality of life (Short Form 36) were assessed at baseline, 6
      weeks, 3 months, and 6 months. RESULTS: At 6 weeks, the assess/advise/treat group
      demonstrated greater improvements in disability, mood, general health, and
      quality of life than patients in the assess/advise/wait group (P < 0.05).
      Disability and pain were not significantly different between the groups at long
      term follow up (P > 0.05). However, mood, general health, and quality of life
      remained significantly better in the assess/advise/treat group (P < 0.05).
      CONCLUSIONS: At short-term, intervention is more effective than advice on staying
      active, leading to more rapid improvement in function, mood, quality of life, and
      general health. The timing of intervention affects the development of
      psychosocial features. If treatment is provided later, the same psychosocial
      benefits are not achieved. Therefore, an assess/advise/treat model of care seems
      to offer better outcomes than an assess/advise/wait model of care.

PMID- 15507795
TI  - A model of experimental spinal cord trauma based on computer-controlled
      intervertebral distraction: characterization of graded injury.
AB  - STUDY DESIGN: : A new model of experimental spinal cord injury is detailed based
      on the application of tensile (distraction) force to the vertebral column of the
      rat. OBJECTIVES: : To develop an experimental model of graded spinal cord injury
      by application of tensile forces to the vertebral column. SUMMARY OF BACKGROUND
      DATA: : Distraction is frequently an integral component of human spinal cord
      injury, but the acute application of tensile forces to the spinal cord has not
      been modeled rigorously. METHODS: : A computer-controlled, motorized outrigger
      device was used to apply a longitudinal stretching force to sublaminar hooks
      oriented proximally at T9 and distally at T11. Distraction force was applied
      using a program that varied the length, speed, and duration of its distraction. A
      modified 14-point Tarlov score was used to establish the presence of hindlimb
      dysfunction. This score was correlated with acute changes in somatosensory-evoked
      potential amplitude, the comprehensive open-field test of locomotor function at 4
      weeks, and postmortem measurements of serotonin content and metabolism in spinal
      cord rostral and distal to the site of injury. RESULTS: : Of distraction
      parameters, only length of distraction correlated significantly with each outcome
      measure. For outcome measures, open-field test inventory and distal/proximal
      ratio of the spinal content of serotonin were correlated most closely with final
      Tarlov scores. Acute somatosensory-evoked potential amplitudes proved to be an
      excellent index of the acute injury but were poor measures of long-term outcome.
      CONCLUSIONS: : Distraction-induced spinal cord injury was uniformly mild in rats
      with intact facet capsular ligaments, regardless of distraction parameters.
      Cutting the facet joint ligaments consistently generated outcome measures
      associated with mild, moderate, and severe spinal cord injury at 3-, 5-, and 7-mm
      distraction lengths, respectively.

PMID- 15507796
TI  - Fas-ligand expression on nucleus pulposus begins in developing embryo.
AB  - STUDY DESIGN: The expression of Fas ligand in the notochord or nucleus pulposus
      was examined immunohistochemically using rat embryos. OBJECTIVE: To clarify at
      which stage of embryo development the expression of Fas ligand begins in the
      nucleus pulposus. SUMMARY OF BACKGROUND DATA: The nucleus pulposus has been
      reported to be an immune-privileged site. Immune-privileged characteristics in
      other tissues, such as the retina and testis, have been attributed to the local
      expression of Fas ligand, which acts by inducing apoptosis of invading Fas
      positive T cells. The authors reported previously on the expression of Fas ligand
      in nucleus pulposus cells of mature rats and humans, which could play a key role
      in the potential molecular mechanism of maintaining immune privilege of the disc.
      However, it is unknown at which stage of the developing embryo Fas ligand
      expression begins in the nucleus pulposus. METHODS: Female adult Sprague-Dawley
      rats were housed with males for one night and monitored the next morning for the
      appearance of a vaginal plug. Later, whole sequential embryos were dissected and
      fixed immediately. Immunohistochemical staining for Fas ligand was performed for
      sagittal sections of notochords or nucleus pulposus using standard procedures.
      The sections were observed using light microscopy. RESULTS: In the 14.5-day-old
      embryo, the notochord appeared as a continuous structure with a uniform diameter,
      and there was no positive staining for Fas ligand. In the 16.5-day-old embryo,
      the notochord became compressed at the centers of the vertebral bodies and
      expanded in the presumptive nucleus pulposus areas. At this stage, some of the
      nucleus pulposus cells exhibited weak positive staining for Fas ligand. In the
      18.5-day-old embryo, the nucleus pulposus enlarged in fusiform, and most of the
      nucleus pulposus cells exhibited intense positive staining for Fas ligand.
      CONCLUSIONS: The present results demonstrated that Fas ligand expression is not
      detected in the notochord, but at the time of intervertebral disc formation, Fas
      ligand expression develops in the nucleus pulposus. These results indicate that
      the immune privilege of the intervertebral disc may begin in the very early
      stages of disc formation. Moreover, Fas ligand may play an important role in the
      formation of the intervertebral disc.

PMID- 15507797
TI  - Age- and region-dependent changes in human lumbar vertebral bone: a
      histomorphometric study.
AB  - STUDY DESIGN: Histomorphometric evaluation of autopsy material. OBJECTIVES: To
      explore region-dependent changes that occur with aging in trabecular and cortical
      bone of the human vertebral body. SUMMARY OF BACKGROUND DATA: Human vertebral
      bone is continuously subjected to external forces (loads) that promote changes in
      inner architecture. This functional adaptability is limited, however, and when
      lost, vertebral bone progressively deteriorates and becomes subject to injury
      with increases in mechanical loading. METHODS: Bone cylinders were drilled with a
      trephine from three regions (central anterior, central posterior, and lateral) of
      the third lumbar vertebral bodies of 48 autopsy cases 31 to 76 years old. Two
      consecutive 5-microm sections obtained 150 microm apart were stained with
      toluidine blue and Masson trichrome and photographed at x40. Differences in
      numerous morphometric factors were evaluated by age and region of the vertebra
      using repeated-measures analysis of variance and Tukey's Honestly Significant
      Difference test. RESULTS: Starting at about 50 years of age, significant,
      linearly progressive decreases occurred in trabecular and cortical bone volume (P
      < 0.005), trabecular surface area (P < 0.001), number of trabeculae (P < 0.001),
      and thickness of trabeculae (P < 0.001). Space between trabeculae increased from
      ages 31 to 70 years and then decreased (P < 0.001). Trabecular deterioration was
      significantly more pronounced in central versus lateral regions (P < 0.001).
      Cortical bone thickness decreased significantly with aging in central regions but
      increased in lateral regions between ages 61 and 70 years (P < 0.001).
      CONCLUSIONS: The balance between cortical and trabecular bone maintains the
      strength of the vertebral body until about the age of 50 years, when irreversible
      deterioration begins in central regions and subsequently involves lateral
      regions.

PMID- 15507798
TI  - Segmental motion adjacent to an instrumented lumbar fusion: the effect of
      extension of fusion to the sacrum.
AB  - STUDY DESIGN: We present an in vitro biomechanical comparison of adjacent segment
      motion at the cranial segment (L3-L4) for an L4-L5 versus an L4-S1 fusion model
      using cadaveric lumbosacral spines. OBJECTIVES: The purpose is to determine the
      biomechanical effect on the unfused cranial segment of extending a short lumbar
      fusion to the sacrum versus stopping at L5. SUMMARY OF BACKGROUND DATA:
      Radiographic evidence of adjacent segment degeneration can occur as a late
      sequela in patients following lumbar and lumbosacral spinal fusions. It is
      believed that altered biomechanics adjacent to the fusion construct contribute to
      these degenerative changes. Little is known regarding changes in cranial adjacent
      segment mechanics resulting from inclusion of the sacrum compared to ending a
      fusion at L5. METHODS: Seven human cadaveric lumbosacral spines were instrumented
      with pedicle screws at L4, L5, and S1. Rods were placed from L4-L5 and from L4-S1
      to simulate the corresponding fusion models. A material testing system was used
      to apply load-controlled moments to the spines in flexion-extension, lateral
      bending, and axial rotation. Electromagnetic sensors were used to record 6 df
      motion across the L3-L4, L4-L5, and L5-S1 motion segments. Angular displacements
      were recorded and system stiffness was calculated for each spine and construct. A
      paired sample t test was used to determine significance of recorded differences.
      RESULTS: Under flexion-extension loading, the angular displacement in the
      sagittal plane at L3-L4 for the L4-S1 model was 9.0 degrees compared to 7.8
      degrees for the L4-L5 model (+15%; P = 0.002). Under lateral bending loading, L3
      L4 motion in the coronal plane for the L4-S1 model was 12.8 degrees and was 14.5
      degrees for the L4-L5 model (-12%; P = 0.002). In axial rotation testing, L3-L4
      torsional motion for the L4-S1 model was equivalent to the L4-L5 model. Overall
      system stiffness increased for the L4-S1 model compared with the L4-L5 model.
      CONCLUSIONS: In this load-controlled model, extending fusion across L5-S1 did not
      consistently increase motion at L3-L4. While it may be difficult to translate
      this finding to a clinical setting, avoiding fusion to the sacrum in a lower
      lumbar fusion may not provide significant benefit from the standpoint of avoiding
      adjacent segment disease.

PMID- 15507799
TI  - Failure characteristics of the thoracic spine with a posteroanterior load:
      investigating the safety of spinal mobilization.
AB  - STUDY DESIGN: In vitro biomechanical study of human cadaveric thoracic spine
      segments and one intact cadaver and applied load measurements in human
      volunteers. OBJECTIVES: To quantify failure load and pattern of midthoracic
      vertebrae under a posteroanterior load and to compare failure load in vitro with
      applied load in vivo. SUMMARY OF BACKGROUND DATA: Osteoporosis and back pain are
      common alone and in combination among older adults. Spinal mobilization
      techniques have been shown to relieve back pain and improve function in various
      clinical settings. However, whether controlled spinal mobilization can cause
      vertebral fracture in individuals with osteoporosis is not known. METHODS: Twelve
      T5-T8 cadaveric specimens (mean age, 77 years) were scanned using bone
      densitometry, radiographed, and measured for bone size. The authors measured
      failure load, failure site, and intervertebral motion (using a precision
      optoelectronic camera system) when a posteroanterior load was applied at the
      spinous process of T6 using a servohydraulic material testing machine. Post-test
      radiography and CT scan were used to verify failure site. These tests were
      repeated in an intact cadaver using a Tekscan I-Scan sensor to measure applied
      loads. The authors also quantified in vivo applied loads during posteroanterior
      mobilization during seven trials by two experienced physiotherapists. RESULTS:
      Mean (SD) in vitro failure load of 479 N (162 N) was significantly higher than
      the mean (SD) in vivo applied load of 145 N (38 N) (P = 0.0004). Macroscopic
      observation revealed a fracture at the T6 spinous process in 11 specimens and one
      at the T7 spinous process. These fractures were detected by plain radiography in
      three of 12 cases and by CT scan in six of 12 cases. CONCLUSIONS: The results
      suggest a reasonable margin between failure load in vitro and applied
      mobilization load in vivo.

PMID- 15507800
TI  - A biomechanical study of regional endplate strength and cage morphology as it
      relates to structural interbody support.
AB  - STUDY DESIGN: An in vitro biomechanical investigation to quantify the endplates
      resistance to compressive loads, in the thoracic and lumbar spine. Comparisons
      were made to determine the regional strength of the endplate, the optimal size
      and geometry of interbody support, and the effects of endplate removal on
      structural strength. OBJECTIVES: To biomechanically assess the regional variation
      of endplate strength in the thoracic and lumbar spine, the optimal geometry and
      cross-sectional area for structural interbody support, and endplate preparation
      techniques with respect to endplate failure or subsidence. SUMMARY OF BACKGROUND
      DATA: Anterior column interbody support plays an important role in spinal
      reconstruction. Subsidence of interbody structural support is a common problem
      and may be related to regional weakness of the endplate, the size and/or geometry
      of structural support, and the preparation of the endplate. Biomechanical data
      related to these issues should be of importance to spine surgeons and reduce the
      risk of subsidence and its inherent complications. METHODS: The indentation tests
      were performed in three subgroups, each with a different set of test variables.
      The first test consisted of 65 vertebrae at six different endplate test positions
      using a 9.53-mm diameter indenter. The second test was performed on 48 vertebrae
      at a central endplate test site using three hollow and two solid cylindrical
      indenters of varying diameter. The third test was done using 24 vertebrae with
      the endplate intact, partially removed, or fully removed. All tests were run
      using human cadaveric specimen using both the superior and inferior endplates.
      The maximum load to failure (MLF) was determined for each test performed.
      RESULTS: For all levels tested, the highest MLF occurred in the posterolateral
      region of the endplate. The lowest value occurred in the central and
      anterocentral regions for levels T7-L5 and T1-T6, respectively. Hollow indenters
      with a small diameter had the lowest MLF, whereas solid large-diameter indenters
      had the highest MLF. The ultimate compressive strength for all hollow indenters
      was significantly higher than all solid indenters. There was a significant
      reduction in the endplate strength with the complete removal of the endplate.
      CONCLUSIONS: The posterolateral region of the endplate provides the greatest
      resistance to subsidence while the central region provides the least resistance.
      A larger-diameter solid support has the greater MLF and the lower the risk of
      subsidence, suggesting a more efficient transfer of force to the endplate with
      the hollow indenters. Parameters such as the geometry of structural support and
      the position and preparation of the endplate can influence the resistance of an
      interbody support to subside. Partial removal of the endplate may provide both,
      for adequate mechanical advantage and a highly vascular site for fusion.

PMID- 15507801
TI  - Cervical spine ligament injury during simulated frontal impact.
AB  - STUDY DESIGN: The supraspinous and interspinous ligaments, ligamentum flavum, and
      capsular and posterior longitudinal ligament strains were monitored during
      simulated frontal impact of whole cervical spine specimens with muscle force
      replication and compared with corresponding physiologic strain limits.
      OBJECTIVES: To quantify the strains in the cervical spine ligaments during
      simulated frontal impact and investigate injury mechanisms. SUMMARY OF BACKGROUND
      DATA: Clinical and biomechanical studies have documented injuries to cervical
      spine ligaments during frontal impact. There are no biomechanical studies
      investigating subfailure injury mechanisms to these ligaments during simulated
      frontal impacts of increasing severity. METHODS: The whole cervical spine with
      muscle force replication model and a bench-top sled were used to simulate frontal
      impacts at 4, 6, 8, and 10 g horizontal accelerations of the T1 vertebra. The
      peak ligament strains during frontal impacts were compared with physiologic
      strain limits determined during intact flexibility testing. RESULTS: Significant
      increases (P < 0.05) in the supraspinous and interspinous ligaments and the
      ligamentum flavum strains beyond physiologic limits were observed throughout the
      cervical spine, with the highest strains occurring at C3-C4. Significant
      increases were observed in the capsular ligament strains only during the 10 g
      impact, whereas the posterior longitudinal ligament strains did not exceed
      physiologic limits. CONCLUSIONS: The supraspinous and interspinous ligaments and
      the ligamentum flavum may be at risk for injury due to excessive strains during
      frontal impacts.

PMID- 15507802
TI  - Correlation between neck injury risk and impact severity parameters in low-speed
      side collisions.
AB  - STUDY DESIGN: In vitro acceleration study on human cadaveric cervical spine
      specimens. OBJECTIVES: To investigate the correlation between the risk to sustain
      a structural cervical spine injury and vehicle-related impact severity
      parameters. SUMMARY OF BACKGROUND DATA: Impact severity parameters, such as the
      peak acceleration of the vehicle, its mean acceleration, and its velocity change,
      are often used to predict the whiplash injury risk or to objectify the patient's
      symptoms even though their correlation to injury is still not well understood.
      METHODS: In a series of three in vitro experiments, a total of 18 human cadaveric
      cervical spine specimens were subjected to incremental side accelerations until
      structural injury occurred. While the duration of the acceleration pulse was kept
      constant throughout all three experiments, its shape was varied: In Experiment I,
      the acceleration pulse had a fast increase up to the maximum value and a fast
      decrease down to zero (fast-fast). Experiment II was characterized by a slow
      increase and fast decrease (slow-fast), and Experiment III was characterized by a
      fast increase and a slow decrease (fast-slow). RESULTS: The specimens of
      Experiment II (slow-fast) sustained structural injury at a significantly higher
      peak acceleration of the sled (4.6 g on average) than those of Experiments I
      (fast-fast) (2.6 g) and III (fast-slow) (3.1 g). In contrast, mean acceleration
      and velocity change of the injuring impacts were almost the same in all three
      experiments. CONCLUSION: The injury risk to the cervical spine was predictable by
      the mean acceleration of the sled and since the duration of the crash pulses was
      constant also by its velocity change but not by its peak acceleration.

PMID- 15507803
TI  - Sensitivity and specificity of outcome measures in patients with neck pain:
      detecting clinically significant improvement.
AB  - STUDY DESIGN: Prospective, single-cohort study. OBJECTIVE: To determine the
      relative sensitivity of a range of outcome measures used in evaluating treatment
      interventions in patients with neck pain and the magnitude of change scores on
      the neck Bournemouth Questionnaire and the cutoff score on the Patients' Global
      Impression of Change scale associated with clinically significant improvement.
      SUMMARY OF BACKGROUND DATA: Traditionally, evaluation of treatment interventions
      using subjective outcome measures has been based on the statistical significance
      of the difference between group mean values. To be clinically meaningful,
      however, information is required from sensitive outcome measures on the
      proportion of patients undergoing a clinically important improvement and from
      this, the number needed to treat for a single patient to benefit. METHODS:
      Patients with nonspecific neck pain from a number of treatment centers completed
      a battery of self-report questionnaires, including the Bournemouth Questionnaire,
      before and after chiropractic treatment. After treatment, patients also completed
      a retrospective analysis of their overall improvement since the start of
      treatment (Patients' Global Impression of Change). The a priori definition of
      clinically significant improvement was defined as a Reliable Change Index on the
      Bournemouth Questionnaire of >1.96. RESULTS: The best cutoffs with a balance
      between the highest sensitivity and highest specificity in detecting clinical
      improvement were a score of 2 or less on the Patients' Global Impression of
      Change (11-point Numerical Rating Scale: 0 = much better, 5 = no change, and 10 =
      much worse) and a raw change score of three or more points on each of the seven
      11-point Numerical Rating Scale subscales of the Bournemouth Questionnaire. For
      the total score of the Bournemouth Questionnaire, raw change scores of 13 or more
      points, percentage change scores of 36% or more, and individual effect sizes of
      1.0 or more were all associated with clinically significant improvement. The
      sensitivity of the Bournemouth Questionnaire in terms of its effect size was
      comparable with that of pain intensity scales and the Neck Disability Index.
      CONCLUSIONS: The present findings will assist in the choice of outcome measures
      in trials on neck pain. The study also illustrates a methodologic framework for
      interpreting change scores in terms of clinical improvement, facilitating the
      process of making sense of research data in the clinical setting.

PMID- 15507805
TI  - Epidural venous plexus enlargements presenting with radiculopathy and back pain
      in patients with inferior vena cava obstruction or occlusion.
AB  - STUDY DESIGN: In the last 2 years, we have examined 9640 patients experiencing
      back pain or sciatica, using MRI. There were 13 (0.13%) patients who had
      radicular symptoms that clinically mimicked lumbar disc herniation or spinal
      stenosis. All of these patients had inferior vena caval obstruction or occlusion
      that caused engorgement in the epidural and paravertebral venous system, causing
      nerve root compression. OBJECTIVE: To illustrate the imaging characteristics of
      13 patients with epidural engorged veins due to inferior vena cava obstruction or
      occlusion causing sciatica and low back pain. SUMMARY OF THE BACKGROUND DATA:
      Abnormalities or pathological changes of epidural venous network may give rise to
      symptoms similar to or mimicking lumbar disc herniation or spinal stenosis.
      Multiple lumbar epidural varices can cause nerve root and thecal sac compression.
      Lumbar epidural varices have been infrequently described in the literature. To
      date, the cause of anterior epidural venous enlargement has been poorly
      understood, and both congenital and acquired causes have been proposed. This
      report describes enlarged epidural veins in patients with inferior vena caval
      thrombosis or obstruction presenting with radicular syndromes. METHODS: The
      authors have seen 13 patients with radicular symptoms. All of the patients had
      inferior vena caval obstruction or occlusion that caused engorgement in the
      epidural veins, causing nerve root compression. The ages of these patients ranged
      from 20 to 53 (mean, 30) years. All of the patients were examined with color
      Doppler ultrasonography and magnetic resonance scanner. RESULTS: Ten of 13
      patients had inferior vena cava thrombosis located just under the renal vein
      orifices. In two patients, there was compression to inferior vena cava due to
      parity. In the remaining patient, a huge intra-abdominal mass was observed, and
      this mass was causing inferior vena cava obstruction and invasion. Enlargements
      of epidural venous plexus were demonstrated in all of these cases. All of the
      patients presented with the acute onset of low back pain followed shortly
      thereafter by acute radicular symptoms. The compression to inferior vena cava
      could not be treated in one patient because of intra-abdominal malignancy. The
      remaining 12 patients with inferior vena cava obstruction or occlusion
      experienced complete resolution of symptoms after treatment or delivery.
      CONCLUSION: The authors believe that epidural venous engorgement should be
      considered when the symptoms of patients with deep venous and inferior vena cava
      thrombosis are accompanied by radicular and/or back pain, because pathologic
      processes compressing a nerve root can cause pain.

PMID- 15507806
TI  - Course of nonsurgical management of burst fractures with intact posterior
      ligamentous complex: an MRI study.
AB  - STUDY DESIGN: Prospective study. OBJECTIVES: To evaluate the results of
      nonsurgical management of burst fractures with intact posterior ligamentous
      complex and to investigate the effect of trauma and/or residual kyphotic
      deformity on adjacent and next adjacent (neighboring) discs. SUMMARY OF
      BACKGROUND DATA: Conservative treatment based on integrity of posterior
      ligamentous complex is controversial, probably because of poor evaluation by
      clinical and indirect radiographic findings. Degenerative changes in the adjacent
      discs due to trauma and/or residual kyphotic deformity is a common expectation.
      MATERIAL AND METHODS: Fifteen consecutive patients who were intact neurologically
      with burst fractures (T11-L2) were treated nonsurgically with the indication
      based solely on the integrity of posterior ligamentous complex determined by MRI.
      Correction of deformity and stabilization with a total body cast under sedation
      were the mainstays of treatment. Patients were mobilized the next day, and casts
      were removed at the end of the third month follow-up period with no further
      external stabilization. Local kyphosis angle, sagittal index, and percent of
      compression of anterior body height were measured on pretreatment, post
      treatment, third month, and latest follow-up radiographs. All of the preoperative
      and latest follow-up MRI studies of the patients were obtained to examine the
      discs adjacent and next adjacent to the fractured levels. The self-reported
      perceptions of the patients of function, pain and appearance were analyzed using
      the Likert Questionnaire. RESULTS: There were eight female and seven male
      patients with an average age of 28 (range, 15-49) years. Average follow-up period
      was 31 (range, 24-51) months. Average local kyphosis angle was found to be 16.5
      degrees (0-34 degrees ) after trauma. It was corrected to 5 degrees (range, 19-25
      degrees ) and deteriorated to 14.6 degrees (range, 2-25 degrees ) at the third
      month and to 17 degrees (range, 2-29 degrees ) at the final follow-up review.
      There was a similar tendency for both sagittal index and percent anterior body
      height. The pretreatment MRI analysis revealed changes in the shape of the discs
      (narrowing or herniation into the body) with no change in the signal intensity of
      nucleus pulposus in eight of the cranial and four of the caudal adjacent discs.
      On follow-up MRI, there was only one intact disc with a normal shape cranially.
      All others had height loss, but only one had complete loss of signal intensity.
      Caudally, two additional discs had changes in shape without any gross changes in
      signal intensity of nucleus pulposus, whereas two had changes in signal intensity
      without change in shape. Only two of the next adjacent discs had changes in shape
      or signal intensity at the time of injury or at latest follow-up review. Average
      score of function, pain, and appearance were 3.9 (range, 3-5), 3.7 (range, 2-5),
      and 3.7 (range, 2-5), respectively, at the latest follow-up review. All patients
      were back at work in 3.6 (range, 1-9) months on average and all were satisfied
      with their treatment. CONCLUSIONS: The present study revealed that an intact
      posterior ligamentous complex might not prevent loss of correction gained by
      nonsurgical management of burst fractures. Significant loss occurs in the first 3
      months despite external stabilization. However, the magnitude of residual
      deformity usually remains close to the initial deformity. Although changes in the
      shape of adjacent discs occur due to trauma and/or natural course, significant
      loss in signal intensity of nucleus pulposus is unlikely. Patient outcome seems
      to be highly satisfactory despite residual deformity.

PMID- 15507807
TI  - Hip-spine syndrome: total sagittal alignment of the spine and clinical symptoms
      in patients with bilateral congenital hip dislocation.
AB  - STUDY DESIGN: The influence of the pathologic state of the hip joint on the total
      sagittal alignment of the spine was investigated in patients with congenital hip
      dislocation retrospectively OBJECTIVE: The purpose of this study was to analyze
      the total sagittal alignment of the spine and the clinical symptoms in patients
      with bilateral congenital hip dislocation. SUMMARY OF BACKGROUND OF DATA:
      Abnormality in the hip joint causes abnormal curvature of the sagittal alignment
      of the spine and induces lumbago or lower leg pain. However, there have been no
      reports on the influence of bilateral congenital hip dislocation on the sagittal
      alignment of the spine. MATERIALS AND METHODS: A total of 9 patients (8 females
      and 1 male) were analyzed. Their average age was 57 years (range, 46-68 years).
      We measured the thoracic kyphosis (T1-T12), the lumbar lordosis (L1-S), the
      sacral inclination (SI), the femoral flexion angle (FFA), pelvic angulation (PA),
      and the distances from the pelvic hip axis (HA) to the C7 plumb line and from the
      promontorium to the C7 plumb line. To evaluate clinical symptoms, we used the
      Japanese Orthopedic Association (JOA) score of low back pain (full score is 29
      points) and Visual Analog Scale (VAS) for lower back pain and lower leg pain, and
      the possible time of walking without rest. RESULTS: The average thoracic
      kyphosis, lumbar lordosis, SI, and PA were 42 degrees , -78 degrees , 68 degrees
      , and 27 degrees , respectively. The FFA averaged 10 degrees , leading to a duck
      like posture. The distances from HA and, promontorium to the C7 plumb line
      averaged -2 cm and 4 cm, respectively. A posterior shift of the gravity line with
      respects to the hips was compensated for by lumbar hyperlordosis, which led to a
      posterior shift of the center of the spine. Regarding the clinical symptoms, the
      JOA score averaged 20 points and the VAS for lower back pain (lumbago) and lower
      leg pain averaged 6.4 and 3.1, respectively. The average possible walking time
      without rest was 20 minutes. CONCLUSION: The total sagittal alignment of the
      spine in patients with bilateral hip dislocation was compensated for by anterior
      angulation of the pelvis and by lumbar hyperlordosis. The main clinical symptoms
      were lower back pain, and not lower leg pain.

PMID- 15507808
TI  - Accurate determination of isthmus of lumbar pedicle: a morphometric study using
      reformatted computed tomographic images.
AB  - STUDY DESIGN: Lumbar pedicle isthmus, the narrowest section of pedicle, was
      investigated. OBJECTIVE: To determine the lumbar pedicle isthmus accurately and
      measure related parameters. SUMMARY OF BACKGROUND DATA: Accurate anatomic
      knowledge of pedicle parameters is critical for a successful transpedicular
      procedure. Many studies on lumbar pedicle dimensions have been conducted, yet
      less is known about how to obtain these data and their veracity. In fact, the
      narrowest section is present in the pedicle, i.e., the isthmus of the pedicle.
      This is the bottleneck of the pedicle; to determine and measure it could
      illustrate the true morphologic characteristics of the lumbar pedicle. METHODS:
      Ultra high-speed spiral CT scan of lumbar spine was performed in 41 patients of
      Chinese origin. After reformation of the original images, isthmus and transverse
      plane of pedicle axis were determined. Eleven dimensions of isthmus plane and
      three dimensions of transverse plane were calculated using software. RESULTS:
      Pedicle endosteal width and height in female patients who were over the age of 50
      were greater than those of female patients younger than 50 years old. The isthmus
      endosteal width from L1 to L5 was 5.2, 6.0, 7.5, 7.5, and 8.7 mm and 4.0, 4.1,
      5.4, 5.7, and 7.1 mm, respectively, in men and women. Isthmus inclination
      inclined to midline with less than 10 degrees above L3 but increased in L4 and 30
      degrees in L5. CONCLUSIONS: An objective narrowest section, the pedicle isthmus,
      exists in lumbar pedicle axis. The parameters of isthmus, especially isthmus
      endosteal width, show the morphologic characteristics of the lumbar pedicle and
      are the most important data provided for transpedicular procedures. The small
      pedicles of female patients over the age of 50 also show certain primary
      osteoporosis. Isthmus inclination puts the pedicle in a more complicated space
      position. A better understanding of the complicated structure of the pedicle
      isthmus guarantees success in transpedicular procedures.

PMID- 15507809
TI  - Intra-abdominal pressure and activation of abdominal muscles in highly trained
      participants during sudden heavy trunk loadings.
AB  - STUDY DESIGN: Ten participants were exposed to heavy sudden trunk loads as they
      might occur during patient handling. OBJECTIVES: The aim was to observe if well
      trained men and women use their full rate of intra-abdominal pressure (IAP)
      development when exposed to heavy sudden trunk loads. Further, to elucidate to
      what degree the rectus abdominus muscle is activated when the IAP is developed.
      SUMMARY OF BACKGROUND DATA: Well-trained judo fighters are used to heavy sudden
      trunk loads and can produce a high IAP. It is unknown whether they use their full
      potential. IAP can increase the spinal stability and has been suggested to unload
      the spine. The unloading effect will, however, disappear if the development of
      the IAP demands substantial activity in the vertical fibers of the abdominal
      muscles. METHODS: Five male and five female well-trained judo and jujitsu
      fighters were exposed to heavy sudden trunk loadings through imitated patient
      handling situations where the patient fell and the fighters should hold the
      patient and prevent the fall. IAP was measured with a catheter in the stomach.
      Along with the IAP measurement, EMG was measured on the abdominal muscles, and
      the load on the low back was quantified by a three-dimensional dynamic
      biomechanical calculation of the torques at the L4-L5 joint. RESULTS: The well
      trained judo fighters did not use their full potential of the IAP development
      when exposed to the heavy sudden trunk loads, but the women had to use a higher
      level of their IAP and extension torque capacity to comply with the heavy loads.
      The rectus abdominus muscle does not contribute to the IAP development when the
      trunk is exposed to a sudden heavy load.

PMID- 15507810
TI  - Persistence and change in nonspecific low back pain among adolescents: a 3-year
      prospective study.
AB  - STUDY DESIGN: This is a 3-year prospective study of juvenile low back pain (LBP).
      OBJECTIVES: To investigate persistence and change in LBP. SUMMARY OF BACKGROUND
      DATA: Earlier episodes of LBP are a strong risk factor for LBP in adults, while
      the persistence of LBP through adolescence is not known. METHODS: The material
      comprised all pupils in eighth and ninth grades (N = 105, mean age 14.7 years),
      living within two geographic areas in Eastern Norway in January 1997. The
      analyses included 88 adolescents at baseline, and 85 at follow-up. The
      questionnaire, which identified LBP as pain or ache in the low back during the
      preceding year, was answered at baseline in the classroom and at follow-up by
      post. RESULTS: LBP was reported by 58% at baseline and by 39% at follow-up, and
      LBP provoked by manual work by 40% at baseline and 26% at follow-up. Thirty-one
      percent reported LBP at both occasions. LBP more than 7 days was reported by 32%
      at baseline, by 26% at follow-up, and by 18% at both occasions. Twenty-two
      percent of those reporting LBP at baseline rejected ever LBP at follow-up.
      Baseline reports of LBP predicted corresponding reports of LBP at follow-up: Odds
      ratio was 4.7 (95% confidence interval 1.7-12.7) for LBP generally, 9.1 (3.0
      27.2) for LBP more than 7 days, 9.2 (2.9-28.8) for LBP provoked by manual work,
      and 3.8 (1.3-11.3) for LBP provoked by sitting at school. CONCLUSION: The
      findings indicate a persistent, but changeable, trend in LBP from midadolescence
      until late adolescence. The consistency and the high rates of reports of LBP
      provoked by manual work and sitting imply needs for more research on the
      persistence of LBP, and on relevant interventions during school age.

PMID- 15507811
TI  - Clinical course in patients seeking primary care for back or neck pain: a
      prospective 5-year follow-up of outcome and health care consumption with subgroup
      analysis.
AB  - STUDY DESIGN: Prospective follow-up. OBJECTIVE: To describe the 5-year clinical
      course in a cohort of patients treated for back or neck pain in primary care and
      compare results with the 1-year outcome both for the whole group and for
      subgroups. SUMMARY OF BACKGROUND DATA: A randomized study showed a decrease in
      perceived pain and disability after treatment by chiropractic or physiotherapy,
      but many reported recurrence or continual pain at the 1-year follow-up. Knowledge
      of the clinical course over longer follow-up periods is limited. METHODS: A 5
      year follow-up questionnaire was sent to 314 individuals. Main outcome measures
      were pain intensity, Oswestry score, and general health. Recurrence, health care
      consumption, and other measures were described. RESULTS: Fifty-two percent of
      respondents reported pain (visual analog scale, >10 mm) and back-related
      disability (Oswestry, >10%) at the 5-year follow-up. This was similar to 1-year
      results, and 84% of these were the same individuals. Sixty-three percent reported
      recurrence or continual pain, and 32% reported health care consumption at the 5
      year follow-up. CONCLUSIONS: In a cohort of individuals of working age seeking
      primary care for nonspecific back or neck pain, it can be expected that about
      half of the population will report pain and disability at the 5-year follow-up. A
      significant proportion will report recurrence or continual pain and health care
      consumption. Pain and disability were associated with recurrence or continual
      pain and health care consumption. Further analysis is needed to identify
      additional predictors for 5-year outcome, taking into account 1-year follow-up
      results. Since many patients will have recurrence or continual pain, health
      policies and clinical decision models for long-term outcome must allow for these
      aspects.

PMID- 15507812
TI  - Traction radiography performed under general anesthetic: a new technique for
      assessing idiopathic scoliosis curves.
AB  - STUDY DESIGN: A prospective review of 24 patients with late-onset idiopathic
      scoliosis. OBJECTIVES.: To compare curve flexibility measured using supine
      bending radiography and traction radiography; to examine the correlation of each
      technique with postoperative correction; and to determine the influence of each
      technique on the decision to perform concomitant anterior release surgery with
      posterior instrumentation. SUMMARY OF BACKGROUND DATA: Assessment of curve
      flexibility is important in decision making before surgical correction of
      scoliosis. Supine bending radiographs are presently the gold standard technique
      by which flexibility is assessed, but their reliability has been questioned. No
      literature has shown a conclusively superior role for traction radiography in
      assessing idiopathic scoliosis curves. METHODS: Each patient had erect
      anteroposterior radiographs and supine bending radiographs. On the day of
      surgery, traction radiography was performed under general anesthetic. The
      correction obtained in the Cobb angle between the bending and traction
      radiographs was compared. The influence of the traction radiography on the
      decision for anterior release surgery and its correlation with postoperative
      result was examined. RESULTS: Traction radiography demonstrated significantly
      greater curve flexibility than supine bending radiographs (P < 0.001). Eleven of
      13 patients planned for anterior release surgery and posterior instrumentation
      avoided anterior release after review of the traction radiography. No significant
      difference was demonstrated between the traction radiography and postoperative
      correction (P = 0.13). CONCLUSION: Traction radiography is superior to supine
      bending radiography in assessing curve mobility before surgery. This method
      benefits patients by allowing them to avoid anterior release surgery and helps
      predict postoperative correction.

PMID- 15507813
TI  - Effectiveness of repeated radiofrequency neurotomy for lumbar facet pain.
AB  - STUDY DESIGN: Retrospective chart review. OBJECTIVES: To determine the success
      rate and duration of relief of repeat radiofrequency neurotomy for lumbar facet
      joint pain. SUMMARY OF BACKGROUND DATA: Radiofrequency neurotomy is an effective
      but temporary management of lumbar facet pain. When pain recurs, radiofrequency
      neurotomy is usually repeated, but the outcome and duration of relief for repeat
      radiofrequency neurotomies are unknown. METHODS: Record review of consecutive
      patients who had an initial successful radiofrequency neurotomy, subsequent
      recurrence of pain, and then repeat radiofrequency neurotomy. Responses of repeat
      radiofrequency neurotomies were compared with initial radiofrequency neurotomy
      for success rates and duration of relief. RESULTS: There were 16 women and 4 men.
      Mean age was 48 years (range, 26-63). Radiofrequency neurotomy denervated one
      segment in two patients, two segments in 16 patients, and three or more in two
      patients. There were 10 bilateral and 10 unilateral radiofrequency neurotomies.
      Mean duration of relief after initial radiofrequency neurotomy was 10.5 months
      (range, 4-19). To date, two patients had a series of two radiofrequency
      neurotomies performed, six had three, five had four, three had five, and four had
      seven or more. Twenty patients had a second radiofrequency neurotomy, which was
      successful in 17 (85%) but unsuccessful in two. The mean duration of relief in 16
      of these 17 patients was 11.6 months (range, 6-19), and relief is continuing in
      one. Sixteen patients had a third radiofrequency neurotomy, of which 15 were
      successful and one was unsuccessful. The mean duration of relief in nine of the
      15 was 11.2 months (range, 5-23), and relief is continuing in the other six.
      Eight patients had a fourth radiofrequency neurotomy, which was successful in
      seven but unsuccessful in one. The mean duration of relief was 9 months (range, 5
      14) in three patients, and relief is continuing in the other four. None of these
      differences is significant. The frequency of success and durations of relief
      remained consistent after each subsequent radiofrequency neurotomy. CONCLUSIONS:
      Repeated radiofrequency neurotomies are an effective long-term palliative
      management of lumbar facet pain. Each radiofrequency neurotomy had a mean
      duration of relief of 10.5 months and was successful more than 85% of the time.

PMID- 15507814
TI  - Re: Khot A, Bowditch M, Powell J, et al. The use of intradiscal steroid therapy
      for lumbar spinal discogenic pain: a randomized controlled trial. Spine
      2004;29:833-7.

PMID- 15507815
TI  - Re: Tulder MW, Touray T, Furlan AD, et al. Muscle relaxants for non-specific low
      back pain: a systematic review within the framework of the Cochrane
      collaboration. Spine 2003;28:1978-92.

PMID- 15507816
TI  - Re: Pengel LHM, Refshauge KM, Maher CG. Responsiveness of pain, disability, and
      physical impairment outcomes in patients with low back pain. Spine. 2004;29:879
      83.

PMID- 15507817
TI  - Complications associated with internal fixation of high-energy bicondylar tibial
      plateau fractures utilizing a two-incision technique.
AB  - OBJECTIVES: Single incision open reduction and double plate fixation of complex
      tibial plateau fractures has been associated with high wound complication rates.
      Minimally invasive methods have been recommended to decrease the wound
      complication rates as compared with open techniques. Additionally, laterally
      applied fixed-angle devices appear to minimize late varus deformity without the
      need for additional medial stabilization. Accurate reduction of comminuted
      lateral and/or medial articular surfaces, however, often requires visualization
      through an open reduction. This study reports the complications, infection rate,
      and radiographic assessment of reduction associated with double plating complex
      AO/OTA 41-C3 tibial plateau fractures utilizing 2 incisions. DESIGN:
      Retrospective clinical review. SETTING: Urban level 1 university trauma center.
      PATIENTS: Over a 77-month period, 83 patients were treated for a complex
      bicondylar tibial plateau fracture at our institution utilizing a 2-incision
      technique. INTERVENTION: Dual plating using anterolateral and posteromedial
      incisions. MAIN OUTCOME MEASURE: Type and incidence of septic and non-septic
      complications and radiographic assessment of articular reduction and axial
      alignment. RESULTS: Eleven fractures were open (13.3%) and classified according
      to Gustilo as type II (1 patient), type III-A (7 patients), type III-B (2
      patients), and type III-C (1 patient). Compartment syndrome was diagnosed and
      treated with fasciotomies in 12 patients (14.5%). The average time interval from
      injury to definitive surgical treatment was 9 days. Seven patients developed deep
      wound infections (8.4%). Three of these had an associated septic arthritis
      (3.6%). Clinical resolution of infection occurred after an average of 3.3
      additional procedures. The presence of a dysvascular limb requiring vascular
      reconstruction was statistically associated with a deep wound infection (P =
      0.006). Secondary procedures for complications included 13 patients who required
      removal of implants secondary to local discomfort, 5 patients who required a knee
      manipulation, 2 patients that were managed with excision of heterotopic
      ossification to improve knee motion, 1 patient that required an equinus
      contracture release, and 1 patient treated for a metadiaphyseal nonunion. Sixteen
      patients (19.3%) incurred deep venous thromboses. No patient was diagnosed with
      pulmonary embolism. Sixty-two percent of patients demonstrated satisfactory
      articular reductions, 91% demonstrated satisfactory coronal alignment, 72%
      demonstrated satisfactory sagittal alignment, and 98% demonstrated satisfactory
      condylar width. CONCLUSIONS: Comminuted bicondylar tibial plateau fractures can
      be successfully treated with open reduction and medial and lateral plate fixation
      using 2 incisions. Dysvascular limbs requiring vascular repair are at increased
      risk for deep sepsis. The use of 2 incisions, temporary spanning external
      fixation, and proper soft-tissue handling may contribute to a lower wound
      complication rate than previously reported.

PMID- 15507818
TI  - The effects of femoral shaft malrotation on lower extremity anatomy.
AB  - OBJECTIVE: To determine how axial rotation around the anatomic axis of the femur,
      as would occur with malrotation of a femoral fracture, affects frontal and
      sagittal plane alignment and knee joint orientation. DESIGN: Computer-generated
      models of the lower extremity were constructed using standardized dimensions. To
      simulate a malrotated fracture, these models were rotated in the shaft around the
      anatomic axis in 15 degrees increments from 60 degrees internal to 60 degrees
      external rotation. Rotation was performed at the proximal fourth, mid-shaft, and
      distal fourth. MAIN OUTCOME MEASUREMENTS: At each rotational position, the
      mechanical axis deviation in millimeters and the changes in mechanical lateral
      distal femoral angle in degrees were measured to quantify frontal plane
      malalignment and malorientation, respectively. The mechanical axis deviation in
      millimeters in the sagittal plane was also measured at each rotatory position.
      RESULTS: Femoral shaft malrotation greater than 30 degrees internal rotation of a
      subtrochanteric fracture or more than 45 degrees of a midshaft fracture or
      external rotation of 30 degrees or greater of a supracondylar fracture resulted
      in frontal plane malalignment. External rotation of a supracondylar fracture of
      45 degrees or more results in knee joint malorientation. Any external rotation at
      all 3 fracture levels caused posterior displacement of the weight-bearing axis in
      the sagittal plane. CONCLUSIONS: Malrotation of a femoral shaft fracture is not
      just a cosmetic problem. Internal and external rotation causes malalignment and
      malorientation in the frontal plane, depending on the level of the fracture and
      the magnitude of malrotation. External rotation of any degree at the proximal
      fourth, mid-shaft, and distal fourth causes a posterior shift of the weight
      bearing axis in the sagittal plane.

PMID- 15507819
TI  - Biomechanics of external fixation of distal tibial extra-articular fractures: is
      spanning the ankle with a foot plate desirable?
AB  - OBJECTIVES: To compare the mechanical stability of external fixation with and
      without spanning of the ankle joint with a foot plate in an in vitro model of
      extra-articular distal tibia fractures. DESIGN: A laboratory investigation was
      performed to evaluate the mechanical behavior of external fixation of extra
      articular distal tibia fractures using a fixator with and without a foot plate.
      Ten fresh-frozen lower extremities (5 pairs) with a simulated OTA 43-A3.3
      fracture were stabilized with an Ilizarov hybrid fixator with and without a foot
      plate. SETTING: All mechanical testing was performed with a servohydraulic test
      frame (MTS Bionix 858, Minneapolis, MN). MAIN OUTCOME MEASUREMENT: Deformation
      characteristics as a function of load were compared for an Ilizarov fixator with
      and without a foot plate under identical conditions of forefoot loading from 0 to
      100 N. Relative interfragmentary motions (vertical and horizontal translations
      and rotation) were measured. RESULTS: There was significantly more vertical
      translation (2.57 +/- 0.97 mm vs. -0.83 +/- 0.64 mm) and angular displacement
      (4.49 +/- 0.45 degrees vs. -1.15 +/- 0.61 degrees ) of the distal fragment in the
      arrangement without a foot plate compared with the construct with a foot plate.
      The anterior translation of the distal fragment was similar with (1.12 +/- 0.98
      mm) and without a foot plate (1.19 +/- 1.23 mm). CONCLUSIONS: This study supports
      the mechanical importance of spanning of the ankle with a foot plate in most
      cases of external fixation for unstable extra-articular and periarticular distal
      tibia fractures. Further studies are needed to validate these results before
      widespread changes in clinical treatment can be recommended.

PMID- 15507820
TI  - The thermal effects of intramedullary reaming.
AB  - OBJECTIVE: To study the effect of tourniquet control on intramedullary reaming.
      DESIGN: An experimental prospective nonsurvival animal study was performed using
      5 mongrel dogs. A pneumatic tourniquet was randomized to either the right or left
      hind limb. Tibial intramedullary reaming was performed with progressively larger
      reamers. Cortical temperatures were measured using thermocouples inserted into
      the tibial diaphyseal cortex. Thermocouples were connected to an analog to
      digital converter that output continuous data that was collected on a computer.
      Upon completion of the procedure, the animals were killed. RESULTS: The peak and
      low temperatures for each thermocouple with each reamer passage were recorded.
      Reamer sizes larger than the internal diameter of the intramedullary canal
      produced higher peak temperatures. The mean delta t (peak temperature minus low
      temperature) was calculated for each reamer passage. This measurement represents
      the overall amount of heat generated during each reamer passage. There were no
      significant differences between the 2 conditions (P = 0.8, paired t test).
      Temperatures decreased in between reamer exchange but did not return to baseline
      levels. CONCLUSIONS: Because similar temperatures were measured both with and
      without a tourniquet, the risk of thermal necrosis appears to be related more to
      the process of intramedullary reaming than to the tourniquet. Higher temperatures
      were measured with reamer sizes larger than the internal diameter of the
      intramedullary canal. Increasing the time interval between the passage of
      successive reamers may allow heat to dissipate and decrease the risk of thermal
      necrosis. The clinical practice of limited reaming ("ream-to-fit") should
      minimize the occurrence of this complication.

PMID- 15507821
TI  - Functional outcomes after open reduction and internal fixation for treatment of
      displaced distal radius fractures in patients over 60 years of age.
AB  - OBJECTIVE: To evaluate the clinical, radiographic, and functional outcomes of
      patients aged 60 and older treated with open reduction and internal fixation
      using plates and screws for displaced and comminuted fractures of the distal
      radius. DESIGN: Retrospective, clinical research. SETTING: Tertiary care center
      (Level 1 trauma center) located in a large urban area. PATIENTS: Eighteen
      patients with an average age of 71 years (range 60-86) form the basis of this
      study. Patients were obtained from a surgical database of 2 hand surgeons in a
      tertiary care center. INTERVENTION: Open reduction and internal fixation of
      fractures of the distal radius using metal plates and screws designed for
      treatment of these injuries. MAIN OUTCOME MEASUREMENTS: Clinical (history and
      physical examination), plain radiographic, and functional assessments were
      performed at an average follow-up of 26 months (range 12-40 months). Functional
      outcomes were assessed using the Gartland and Werley and Disabilities of the Arm,
      Shoulder, and Hand scoring systems. RESULTS: Satisfactory reduction was achieved
      in all 18 fractures at the time of operative fixation with no instances of loss
      of fracture reduction during the study period. There were no cases of malunion,
      nonunion, or instances of device failure. We identified 4 minor complications. No
      patients required reoperation. Fifteen patients had an excellent (83%) and 3 had
      a good (17%) result according to the Gartland and Werley scoring system. The mean
      Disabilities of the Arm, Shoulder, and Hand score was 4.4 (range 0-14) out of a
      maximum 100. CONCLUSION: Our findings suggest that open reduction and internal
      fixation with plates and screws in patients 60 years and older with displaced and
      comminuted fractures of the distal radius represents a safe and effective
      treatment alternative.

PMID- 15507822
TI  - Characterization of a closed femur fracture model in mice.
AB  - OBJECTIVES: The goal of this study was to develop and characterize a closed femur
      fracture model for mice that can be used for the molecular and genetic analysis
      of fracture healing. STUDY DESIGN: Longitudinal time study of species-specific
      fracture healing. METHODS: A protocol was developed for creating reproducible,
      closed femur fractures in mice. Impending fractures were stabilized by retrograde
      insertion of a 0.01-inch-diameter, stainless steel wire into the intramedullary
      canal. The intramedullary wire was held in place with a wedge made from the first
      2 mm of a 30-gauge needle. Fractures were produced by 3-point bending. Fracture
      healing was assessed by radiography, histology, and torsional mechanical testing.
      RESULTS: The mouse femur fracture technique produced good results with minimal
      loss of animals. Of the 246 mice used in the study, 22 mice were excluded due to
      poor fracture quality (8), loss of fracture stabilization (6), or to anesthesia
      death (8). Radiography showed a consistent pattern of fracture healing between
      mice with peak fracture callus volume evident at 10 (15 mice) to 14 days (18
      mice) after fracture. Fracture bridging was apparent in all 3-week postfracture
      radiographs (35 mice). Histologic examination of 117 specimens at 9 time points
      showed chondrocyte differentiation within the fracture callus by 7 days after
      fracture, endochondral ossification occurring by 10 days after fracture, and bone
      remodeling evident as early as 3 weeks after fracture. Despite radiologic and
      histologic evidence of fracture bridging after 3 weeks, torsional mechanical
      testing of 68 mice at 3, 4, 6, and 12 weeks after fracture (group size of 15 to
      18 mice at each time point) indicated that significant increases in structural or
      material strength did not occur until 6 to 12 weeks after fracture. CONCLUSIONS:
      Femur fracture healing in mice follows a typical endochondral ossification
      pathway with fracture bridging occurring approximately 1 week faster in mice than
      rats. This fracture model is amenable to the molecular and genetic analysis of
      fracture healing using different inbred, transgenic, and knockout strains of
      mice.

PMID- 15507823
TI  - A modified judet approach to the scapula.
AB  - Operative treatment of scapula fractures is uncommon, but is indicated for
      significantly displaced fractures or intra-articular fractures. This modified
      Judet approach for exposure of scapula fractures combines several important
      goals: 1) exposure of all bony elements of the scapula which have adequate bone
      stock for internal fixation; 2) minimal trauma to the rotator cuff musculature;
      and 3) protection of the major neurologic structures (suprascapular nerve
      superiorly and axillary nerve laterally). The main advantage of the exposure is
      limiting muscular dissection, which can potentially improve rehabilitation and
      limit morbidity of the operation.

PMID- 15507824
TI  - Spontaneous defect remodeling in a distal humerus fracture with extensive osseous
      loss: a case report of a complex elbow fracture.
AB  - Sideswipe injuries to the elbow cause complex fracture patterns and remain
      difficult management problems. The authors report a case of spontaneous bone
      remodeling of an extensive metaphyseal defect zone.

PMID- 15507827
TI  - Surgical options for broken intramedullary nail.

PMID- 15507828
TI  - [An opportunity to grab].

PMID- 15507829
TI  - [Anatomy of the heart and coronary arteries].
AB  - Orientation and morphology of the heart and coronary vessels are the basis of
      cardiac imaging. Knowledge of the configuration of cardiac cavities within the
      thorax and of the course of coronary vessels is mandatory in order to plan and
      carry out magnetic resonance imaging acquisitions and computed tomographic
      reformations. These anatomical features are described, with focus on useful data
      for acquisition and interpretation of imaging studies. MR and CT images will be
      presented.

PMID- 15507830
TI  - [Anatomy of the heart and coronary arteries].

PMID- 15507831
TI  - [Assessment of cardiac function by magnetic resonance and multislice spiral
      computed tomography].
AB  - Magnetic resonance imaging and multislice spiral computed tomography are ideal
      techniques for assessing cardiac function. The main objectives of this article
      are to describe the different aspects, global and regional systolic left
      ventricular function, diastolic left ventricular function and right ventricular
      function, and to introduce the agreed parameters for this evaluation.

PMID- 15507832
TI  - [Assessment of cardiac function by magnetic resonance and multislice spiral
      computed tomography].

PMID- 15507833
TI  - [Multislice CT and MRI of coronary artery disease: current and future role].
AB  - If the role of multislice CT and MRI is not clearly defined in ischemic heart
      disease, these new cardiac imaging techniques are very promising due to recent
      technological advances. The detection of coronary artery plaque and stenosis, as
      well as coronary bypass graft and stenting patency, the evaluation of left
      ventricular remodeling after infarction, are available in routine with a 16
      slices multislice CT. MRI is the technique of choice to appreciate the impact of
      a coronary artery lesion on myocardium: detection of ischemia by first-pass
      perfusion imaging at rest and under pharmacological stress, detection and
      extension of infarcted myocardium and assessment of myocardial viability. The
      potential indications will be discussed for each technique in the light of the
      main clinical questions asked by the cardiologist in daily practice.

PMID- 15507834
TI  - [Multislice CT and MRI of coronary artery disease: current and future role].

PMID- 15507836
TI  - [Noninvasive coronary artery imaging: CT and MR].

PMID- 15507835
TI  - [Noninvasive coronary artery imaging: CT and MR].
AB  - The advent of helical multidetector CT has significantly modified several
      traditional clinical approaches to cardiovascular diagnosis. The current
      availability of rapid image acquisition has provided the basis for investigating
      direct imaging in real time of cardiac structures using CT. Application of thin
      section submillimetric image acquisitions to three-dimensional (3D)
      reconstruction algorithms produces 3D data sets from which images of the coronary
      arteries may be obtained in any anatomic plane. The advantage of the
      submillimetric isotropic spatial resolution is partly offset by reduced temporal
      resolution as well as reduced contrast resolution compared to MRI. This lack in
      contrast sensitivity prevents accurate perfusion imaging and restricts the
      clinical use to coronary artery imaging. Moreover, the large amount of iodinated
      contrast medium injected has potential nephrotoxic effects, which can be
      deleterious if coronary artery angiography must to be performed. On the other
      hand, MRI has less spatial resolution, and acquisitions must be performed in the
      plane of each coronary artery because of reduced volume coverage. Both techniques
      play a role in the non-invasive assessment of coronary artery disease, by
      providing complementary information already useful in a growing number of
      clinical situations.

PMID- 15507837
TI  - [Ischemic heart disease (myocardial perfusion and viability): techniques and
      results].
AB  - Over the last two decades, the understanding, diagnosis and treatment of patients
      with suspected or known coronary artery disease have made tremendous progress, in
      particular with the help of the development of non-invasive methodologies for
      assessing myocardial perfusion and viability. Clinically, nuclear medicine
      techniques (particularly SPECT imaging) have predominated. With the recent
      technical developments allowing for a combined assessment of perfusion and
      irreversible damage with late enhancement imaging, MRI will now play a major role
      in the assessment of ischemic heart disease.

PMID- 15507838
TI  - [Ischemic heart disease (myocardial perfusion and viability): techniques and
      results].

PMID- 15507839
TI  - [Value of MRI in the evaluation of congenital anomalies of the heart and great
      vessels].
AB  - Management of congenital heart diseases (CHD) frequently is a diagnostic
      challenge. MRI, as a complement to echocardiography, plays an important role in
      the non-invasive evaluation of these anomalies. MRI allows high resolution
      anatomical evaluation of these structures in multiple planes as well as
      functional evaluation. These features are helpful to further characterize extra
      cardiac anomalies that may be difficult to assess at US and even angiography. MRI
      is thus a valuable imaging tool in the evaluation of CHD.

PMID- 15507840
TI  - [Value of MRI in the evaluation of congenital anomalies of the heart and great
      vessels].

PMID- 15507841
TI  - [Pericardium and cardiac valves: value of MRI and Multislice CT].
AB  - Color Doppler echocardiography has limitations, particularly in the assessment of
      valvular regurgitation and pericardial diseases. MRI, with the help of three
      dimensional morphologic data, dynamic acquisitions with cine techniques and
      functional evaluation with flow sensitive techniques can be envisioned as a
      complementary noninvasive procedure able to provide the complete information
      required for planning therapeutic options. Qualitative as well as accurate and
      reproducible quantitative information (volume measurements, cardiac function and
      flow velocity profiles) are unique for the evaluation of the severity of valve or
      pericardial diseases. Multislice CT is unique in precisely demonstrating valvular
      and pericardial calcifications. This article reviews both imaging techniques used
      in assessing valvular and pericardial disease and discusses the advantages and
      limitations of these techniques in current clinical applications.

PMID- 15507842
TI  - [Pericardium and cardiac valves: value of MRI and Multislice CT].

PMID- 15507843
TI  - Fish protein improves the total antioxidant status of streptozotocin-induced
      diabetes in spontaneously hypertensive rat.
AB  - BACKGROUND: We measured the effects of fish protein (FP) on blood pressure,
      glycemia and antioxidant status in spontaneously hypertensive (SH) rats with
      streptozotocin-induced diabetes (STZ). MATERIAL/METHODS: Two groups of 12 rats
      each were fed 20% casein (C) or FP for 2 months. The total antioxidant status of
      blood and organs (liver, kidney and heart) was measured by the KRL test.
      Antioxidant enzyme activities (G-Px, G-Red, and SOD) and antioxidant substances
      (GSH, NO) were determined in organs, and vitamin C in plasma. RESULTS: FP lowered
      blood pressure in SH rats, but not in SH-STZ. Blood and plasma antioxidant status
      increased 35% and 9%, respectively, with FP in SH-STZ compared to SH rats; when
      compared to C, these values were more enhanced. SOD activity values were elevated
      with FP in SH-STZ rats, compared to the C diet, regardless of organ. Higher
      kidney NO and heart GSH values were noted in SH-STZ rats than SH. In SH rats fed
      FP, the GSH value was 2.26 times higher in liver, and NO was 3 times higher in
      heart. Higher NO was noted in kidney (1.84 times) and heart (1.91 times), GSH in
      heart (1.79 times), and vitamin C in plasma (+46%) in SH-STZ rats with FP than
      with C. CONCLUSIONS: Fish protein has a beneficial effect on blood pressure in SH
      rats but not in SH-STZ, and plays an important role in antioxidative defense.
      This protein may be useful in future treatments of such diseases as diabetes and
      hypertension.

PMID- 15507844
TI  - The effect of 5-aminolevulinic acid-based photodynamic treatment (PDT) on
      nucleoli of leukemic granulocytic precursors represented by K562 blastic cells in
      vitro.
AB  - BACKGROUND: Since photodynamic treatment (PDT) induces apoptosis in individual HL
      60 cells originating from early granulocytic precursors of acute myeloid
      leukemia, the present study was undertaken to provide information on such
      treatment of K562 cells, which originate from early granulocytic precursors of
      chronic myeloid leukemia (blastic phase) and carry the bcr/abl fusion gene with
      anti-apoptotic properties. MATERIAL/METHODS: PDT was based on the 5
      aminolevulinic acid treatment of K562 cells, followed by blue light irradiation
      under conditions which in HL-60 cells induce an apoptotic process without
      previous terminal maturation. Nuclei and nucleoli were visualized by cytochemical
      procedures to demonstrate DNA, RNA and silver stained proteins of nucleolus
      organizer regions (AgNORs). TUNEL and propidium iodide assays were used for
      additional control of the incidence of apoptotic and necrotic cells. RESULTS: In
      contrast to HL-60 cells, PDT did not induce apoptosis in K562 cells. However,
      after PDT some K562 cells exhibited major alterations, expressed by nuclear and
      cell swelling, reflecting a necrotic process, confirmed by propidium iodide. In
      addition, PDT produced a reduction of AgNORs, though smaller than that previously
      described in apoptotic HL-60 cells. CONCLUSIONS: PDT produced only necrotic
      changes in some K562 cells under conditions which induced in apoptosis in HL-60
      cells. Thus the induction of apoptosis, nuclear and nucleolar changes in
      individual cells does not depend on the inducer--PDT--but on the cell properties.

PMID- 15507845
TI  - Angiotensin II and its fragments (angiotensins III and IV) decrease the growth of
      DU-145 prostate cancer in vitro.
AB  - BACKGROUND: There is growing evidence that angiotensin II (AngII) and its smaller
      fragments 2-8 (AngIII) and 3-8 (AngIV) are involved in cell-growth control in the
      vascular smooth muscle and in some other tissues, including prostate. The aim of
      this paper was to investigate the effects of AngII and its fragments AngIII and
      AngIV on the growth of an androgen-independent human prostate cancer cell line in
      vitro. To see whether the conversion of Ang II into its shorter fragments plays a
      role in the action of the former, we used specific inhibitors of aminopeptidases:
      compound EC33 (inhibitor of aminopeptidase A), which blocks the conversion of
      AngII into AngIII, and compound PC 18 (inhibitor of aminopeptidase N), which
      blocks the conversion of AngIII into AngIV. MATERIAL/METHODS: Human prostate
      cancer DU-145 cells were exposed in culture to different concentrations of AngII,
      AngIII, and AngIV separately or jointly with the aminopeptidase inhibitors EC33
      or PC18. To measure cell growth, the colorimetric method, based on the reduction
      of tetrazolium salt by viable cells, was applied. RESULTS: It was found that
      exposure of DU-145 cells in vitro to all the investigated angiotensins resulted
      in a moderate, concentration-dependent inhibition of cell growth. The joint
      exposure of DU-145 cells to AngII plus EC33, but not to AngII plus PC 18,
      abolished the effect of AngII. CONCLUSIONS: These findings suggest that
      angiotensin peptides (AngII as well as its smaller fragments) are involved in the
      negative control of prostate cancer cell growth.

PMID- 15507846
TI  - Genistein alone or combined with cyclophosphamide may stimulate 16/C
      transplantable mouse mammary cancer growth.
AB  - Among the many potential antiangiogenic agents now in various stages of
      preclinical or clinical study, genistein (GEN) has generated wide interest being
      because of its natural origin (soybeans) and epidemiological studies showing the
      cancer chemopreventive effects of soybean consumption. In this paper the in vivo
      effects of GEN applied either alone or together with cyclophosphamide on the
      growth of mouse transplantable mammary carcinoma (16/C) transplanted either
      orthotopically or ectopically is presented. The growth of 16/C mouse mammary
      cancer transplanted subcutaneously (s.c.) or into the mammary gland
      (orthotopically-orth.) was stimulated by GEN administered from day 4 after tumor
      cell inoculation. Such stimulation was not observed when the treatment with GEN
      was started at day 12 after cell inoculation. Stimulation of tumor growth by GEN
      was markedly higher in mice transplantedorth. than in those transplanted s.c..
      However, GEN did not affect the expression of estrogen (ER)and progesterone
      receptors (PgR) in the orthotopic model of 16/C cancer. In the case of
      subcutaneously growing tumors, treatment with GEN lowered (2-fold) the expression
      of both ER and PgR. In the interpretation of these results, the pleiotropic
      (including hormonal and antiproliferative), sometimes opposing effects of
      genistein in vivo should be considered. It seems rather reasonable to exclude
      breast and, perhaps, other hormone-dependent cancers from the treatment and
      chemoprevention with soy-derived phytoestrogens until its mechanism(s) of action
      on various cancer cells is completely understood.

PMID- 15507847
TI  - Interferon-gamma impedes reverse cholesterol transport and promotes foam cell
      transformation in THP-1 human monocytes/macrophages.
AB  - BACKGROUND: Cholesterol 27-hydroxylase, an enzyme expressed at high levels by
      human monocytes/macrophages, provides a first line of defense against the
      development of atherosclerosis. Prior studies have suggested that the cytokine
      interferon-gamma (IFN-gamma) promotes atherosclerosis. We therefore examined the
      effect of IFN-g on macrophage foam cell formation and on expression of the anti
      atherogenic 27-hydroxylase in THP-1 human monocytes/macrophages.
      MATERIAL/METHODS: THP-1 monocytes and acetylated LDL-treated THP-1 macrophages
      were incubated in the presence or absence of IFN-gamma (500 U/ml) with or without
      the addition of IFN- gamma receptor blocking or neutralizing antibody. Foam cell
      formation was quantified based on percentage of macrophages harboring oil red O
      stained globules. Cellular mRNA and protein were isolated. 27-Hydroxylase message
      was measured by RT-PCR and 27-hydroxylase protein by immunoblot. RESULTS: IFN
      gamma -treated THP-1 macrophages exhibit increased foam cell transformation
      compared to untreated cells under cholesterol loading conditions. IFN-gamma
      promoted foam cell formation is abolished by pre-treatment with either IFN-gamma
      neutralizing or IFN-gamma receptor blocking antibody. IFN-gamma diminishes
      cholesterol 27-hydroxylase expression in THP-1, and this IFN-gamma -induced
      downregulation is prevented by pre-treating the cultured cells with either IFN
      gamma neutralizing or IFN-gamma receptor blocking antibody. CONCLUSIONS:
      Imbalances in cellular cholesterol flux within macrophages lead to formation of
      lipid-laden foam cells, a critical step in the pathogenesis of atherosclerosis.
      We have demonstrated that IFN-gamma, acting through the IFN-gamma receptor,
      decreases expression of 27-hydroxylase and increases propensity to foam cell
      formation in the cell line THP-1. These observations suggest that one mechanism
      by which IFN-g promotes atherosclerosis may involve affecting expression of
      cholesterol 27-hydroxylase, a cholesterol homeostatic protein.

PMID- 15507848
TI  - Quantitative fish determination of chromosome 3 arm imbalances in lung tumors by
      automated image cytometry.
AB  - BACKGROUND: Clonal heterogeneity is a major difficulty in the analysis of
      chromosome rearrangements within tumor tissue. Using in situ hybridization, a
      cell-to-cell analysis can be performed and should allow a better understanding of
      the genetic process. In addition, detection of pre-neoplastic lesions with only a
      few cells involved may improve the diagnosis of such lesions and their precocious
      treatment. MATERIAL/METHODS: Automated analysis was performed on tissue sections
      with our previously described two-color fluorescence in situ hybridization-based
      method for quantitative determination of chromosome arm imbalance. The imbalance
      between the long and short arms of chromosome 3 was determined in 24 cases of non
      small-cell and small-cell lung cancers in which only small snap-frozen sections
      were used, allowing other simultaneous molecular analyses, such as TP53 gene
      mutation detection. RESULTS: Specifically developed software allowed localization
      of each nucleus within the section with regard to its chromosome imbalance and to
      reconstitute a multi-clonal panel within an apparently homogeneous sample. In
      some cases, discrepancies in the imbalance values were observed between the
      biopsy and the tumor obtained after surgery from the same patient. CONCLUSIONS:
      The discrepancies observed between biopsies and tumors, likely linked to the
      samples' heterogeneity, demonstrate the necessity to analyze tissue sections
      collected at various locations. The fully automated approach developed in this
      study rendered such investigations possible.

PMID- 15507849
TI  - Urinary levels of interleukin-6 and interleukin-8 in children with urinary tract
      infections to age 2.
AB  - BACKGROUND: The aim of this study was to assess relations between the clinical
      course of UTI, IL-6 and IL-8 levels, and the presence of inflammatory changes
      detected by renal scintigraphy using 99mTc-DMSA (DMSA). MATERIAL/METHODS: We
      studied 33 children aged 1-24 months (mean 7.1+/-5.8 months) with first-time UTI.
      The subjects were divided in two groups: with fever (group I, n=10) and without
      fever (group II, n=23). Inflammatory markers (ESR, CRP, leukocyte count), urinary
      IL-6 and IL-8 level, and DMSA scan were evaluated in all children. RESULTS:
      Urinary IL-6 and IL-8 levels [IL-6, IL-8/creatinine (pg/mg)] were significantly
      higher in group I than in group II (Il-6 level: 39.4+/-41.1 vs. 6.3+/-13.7,
      p<0.01; IL-8 level: 791.1+/-1143.6 vs. 36+/-87.9, p<0.001). We found positive
      correlation between urinary IL-6 and IL-8 levels and ESR, CRP, and leukocyte
      count (IL-6: r=0.43, p<0.05; r=0.46, p<0.05; and r=0.59, p<0.001, respectively;
      IL-8: r=0.55, p<0.05; r=0.72, p<0.0001; and r=0.44, p<0.05, respectively). We
      found no relation between urinary cytokine levels and the presence of
      inflammatory changes detected by DMSA scanning, despite slightly higher mean
      urinary cytokine levels in children with inflammatory changes in DMSA scan.
      CONCLUSIONS: We found significantly higher IL-6 and IL-8 levels in children with
      febrile UTI and elevated inflammatory markers. IL-6 and IL-8 levels do not
      differentiate between acute pyelonephritis and UTI in children to age 24 months.

PMID- 15507850
TI  - Plasmid-mediated multiple antibiotic resistance in Proteus mirabilis isolated
      from patients with urinary tract infection.
AB  - BACKGROUND: Worldwide surveillance of antimicrobial resistance among urinary
      tract pathogens is useful to determine important trends and geographical
      variation for common Gram negative and positive species. We initiated this study
      to learn the drug resistance pattern and its location (genomic or plasmid-borne)
      among the strains of Proteus mirabilis, one of the most common causative agents
      of urinary tract infection (UTI). MATERIAL/METHODS: A total of 200 urine samples
      were collected from UTI patients, followed by isolation and identification of
      Proteus milabilis strains. Antibiotic sensitivity and resistance analysis was
      performed by the disc diffusion method, employing multiple antibiotic discs. The
      sensitivity was monitored by visualizing the zone of inhibition around the disc.
      Plasmid isolation was performed by the method of Kado and Liu. Transfer of the R
      Plasmid to recipient E.coli C600 cells was achieved using the method of Lederberg
      and Cohen. RESULTS: Clinical study revealed that this infection is more common in
      young pregnant women. Various strains of Proteus mirabilis isolated during the
      course of the study were found to show multiple antibiotic resistance, which was
      further characterized as plasmid-borne drug resistance. CONCLUSIONS: Proteus
      mirabilis is one of the important causative agents of urinary tract infection in
      young women especially during the state of pregnancy. Multiple antibiotic
      resistance markers of Proteus strains were identified as plasmid mediated.

PMID- 15507851
TI  - Short stature in beta-thalassemia minor subjects.
AB  - BACKGROUND: Numerous disturbances in growth and development have been observed
      and demonstrated in homozygote beta-thalassemia patients. However, short stature
      in thalassemia minor subjects, who have a minor defect in hemoglobin chain
      synthesis, has not yet been studied. MATERIAL/METHODS: In this cross-sectional
      study, the heights of 100 thalassemia minor subjects in the age group of 2-18
      years and their parents were measured and analyzed. If the subject were in the 3
      10 percentile range of height based on standardized sex and age curves, several
      follow-ups with complete history and physical examinations for a period of one
      year were preformed. If the healthy carrier's height was below the 3rd
      percentile, history, physical examination, and paraclinical examinations,
      including BUN, creatinine, electrolytes, serum alkaline phosphatase, thyroid
      function tests, growth hormone and cortisol levels, arterial blood gas,
      radiography of the left hand and wrist, etc, were also checked. One hundred
      healthy children were randomly chosen as a control group and matched for
      demographic characteristics with our healthy carrier subjects. RESULTS: Mean +/-
      standard deviation for the age of our subjects was 6.62+/-3.63 years old. Twenty
      seven (27%) of the patients had short stature. Except for hemoglobin (with a mean
      of 11.5 g/l), all other paraclinical data were normal. CONCLUSIONS: We concluded
      that short stature was significantly more prevalent in the healthy beta
      thalassemia minor subjects than in the control group (p<0.001). Therefore,
      thalassemia minor can cause short stature.

PMID- 15507852
TI  - Carotid artery atherosclerotic plaque: clinical and morphological
      immunohistochemical correlation.
AB  - BACKGROUND: The purpose of the study was to: 1) investigate carotid
      atherosclerotic plaque morphology and immunohistochemistry (IHC) with respect to
      the localization sites of Chlamydia pneumoniae, 2) find correlations between
      plaque morphology and clinical sonographical characteristics, and 3) determine
      the correlation between abundance of C. pneumoniae and complexity of the plaque.
      MATERIAL/METHODS: 200 patients with asymptomatic (A=59) and symptomatic (S=141)
      courses of carotid stenosis admitted to the Neurology and Neurosurgery Clinic for
      TIA or acute ischemic stroke were studied. For IHC the atherosclerotic plaques
      were incubated with primarily monoclonal anti-Chlamydia pneumoniae antibody clone
      RP402, code no. M6600, diluted 1:50 (DAKO). Statistical evaluation was performed.
      RESULTS: 34 (17%) homogeneous (HO), or stable, and 166 (83%) heterogeneous (HE),
      or unstable, plaques were divided into 3 HO and 5 HE subtypes according to the
      number of histopathological signs and prevalence of inflammatory cell types,
      having different sonographical characteristics and plaque thickness. Complex
      plaques of both A and S patients have activation signs for chronic inflammation,
      phagocytosis, and atheromatosis: all three of these in HE plaque subtypes, and
      only for atheromatosis in HO plaques. CONCLUSIONS: 1) C. pneumoniae IHC signals
      were found in every kind of phagocyte (histiocytes, macrophages, foreign body
      macrophages, foam cells, PMNs) located in the fibrous cap, atheroma (necrotic
      core), and especially at the boundary of fibrous cap/atheroma; 2) complexities
      were found, so plaque instability signs strongly correlate with abundance of C.
      pneumoniae (p<0.001); 3) sufficient correlation between plaque thickness and
      disease symptomaticity (p<0.01) was found.

PMID- 15507853
TI  - A proposal of criteria for the classification of systemic sclerosis.
AB  - BACKGROUND: Sensitive and specific criteria for the classification of systemic
      sclerosis are required by clinicians and investigators to achieve higher quality
      clinical studies and approaches to therapy. A clinical study of systemic
      sclerosis patients in Europe and Canada led to a set of criteria that achieve
      high sensitivity and specificity. MATERIAL/METHODS: Both clinical and laboratory
      investigations of patients with systemic sclerosis, related conditions and
      diseases with clinical features that can be mistaken as part of the systemic
      sclerosis spectrum were undertaken. Laboratory investigations included the
      detection of autoantibodies to centromere proteins, Scl-70 (topoisomerase I), and
      fibrillarin (U3-RNP). RESULTS: Based on the investigation of 269 systemic
      sclerosis patients and 720 patients presenting with related and confounding
      conditions, the following set of criteria for the classification of systemic
      sclerosis was proposed: 1) autoantibodies to: centromere proteins, Scl-70 (topo
      I), fibrillarin; 2) bibasilar pulmonary fibrosis; 3) contractures of the digital
      joints or prayer sign; 4) dermal thickening proximal to the wrists; 5) calcinosis
      cutis; 6) Raynaud's phenomenon; 7) esophageal distal hypomotility or reflux
      esophagitis; 8) sclerodactyly or non-pitting digital edema; 9) teleangiectasias.
      The classification of definite SSc requires at least three of the above criteria.
      CONCLUSIONS: Criteria for the classification of systemic sclerosis have been
      proposed. Preliminary testing has defined the sensitivity and specificity of
      these criteria as high as 99% and 100%, respectively. Testing and validation of
      the proposed criteria by other clinical centers is required.

PMID- 15507854
TI  - Review of clinical and toxicological features of acute pesticide poisonings in
      Crete (Greece) during the period 1991-2001.
AB  - BACKGROUND: In Crete, the largest island of Greece, many pesticide formulations
      are increasingly used in agriculture in order to raise crop production. This
      study reviews a number of pesticide poisoning cases registered at the Center of
      Toxicology and Forensic Sciences Research at the University of Crete between 1991
      and 2001. MATERIAL/METHODS: The medical records and toxicological data of the
      pesticide poisonings are presented. The analyzed samples were mainly blood and/or
      urine, but also gastric fluids and other tissues. Analysis involved a variety of
      techniques. RESULTS: Eleven poisonings caused by paraquat (7 men, 4 women, aged
      15-58 years) are reported, five of which had fatal outcome. Initial paraquat
      plasma levels ranged between 0.4-165 pg/ml. Thirteen intoxications due to various
      organophosphorous agents are presented (11 men, 2 women, aged 13-69 years).
      Pesticide blood levels upon admission ranged from 1.0-108 pg/ml and there were
      six fatalities. Carbamate poisonings (4 men, 2 women, aged 32-60 years) were
      caused by methomyl (initial blood levels 1.6-57 mg/l) and resulted in death. A
      case of methyl bromide intoxication is also presented. CONCLUSIONS: The results
      of the study highlight the toxic and potentially lethal effects of pesticide
      formulations used in agriculture. Special seminars should be run to educate
      farmers on the proper use of these agents and the supply of pesticides should be
      restricted to those who follow all safety measures. Physicians should be trained
      to promptly identify and treat pesticide intoxications.

PMID- 15507855
TI  - Patterns of agreement on breast cancer screening knowledge and practices among
      women in Dominican and Mexican families in New York City.
AB  - BACKGROUND: In medically underserved communities, the transfer of information
      through social networks may help promote healthy behaviors when traditional
      health education channels are not effective. MATERIAL/METHODS: A cross-sectional
      survey was conducted with 212 young Mexican and Dominican women and 212 of their
      older female relatives (age 40-88) regarding knowledge and practices of breast
      cancer screening, allowing analysis of agreement between women of different
      generations in the same family. RESULTS: Women in the study had low educational
      attainment and had poor access to health care. Two-thirds of all participants
      reported that they talked to their relatives about breast cancer screening; these
      women were significantly more likely to perform BSE, but not to have had clinical
      breast exams or mammograms. Measurement of prevalence-adjusted bias-adjusted
      kappa between the 212 family pairs found agreement on knowledge of the various
      screening methods and on sources of health information, but not on BSE or
      clinical breast exam behavior. CONCLUSIONS: These mixed findings do not suggest a
      direct relationship between information sharing within a family and screening
      behavior. An innovative model of training young women connected to regular
      medical care to convey information and reinforce existing educational messages
      for the older women in their families may be successful. But the lack of a
      pattern of similar screening behaviors within the family pairs indicates that any
      such effort would need to begin by providing the young women with accurate
      information about screening.

PMID- 15507856
TI  - Severe sepsis in Poland--results of internet surveillance of 1043 cases.
AB  - BACKGROUND: Severe sepsis is a clinical syndrome frequently occurring in
      intensive care units (ICUs) when systemic infection results in multiorgan
      dysfunction. No Polish data concerning treatment and prognosis in this group of
      patients have been available to date. MATERIAL/METHODS: The Polish Working Group
      for Sepsis introduced in 2003 internet registration of severe sepsis cases
      treated in ICUs in Poland. Information about severe sepsis were entered including
      the type of infection, clinical course, methods and results of treatment.
      RESULTS: From 20.04.2003 to 10.01.2004, 1043 severe sepsis cases were reported by
      104 ICUs. Mean age of patients was 59 years. Mean duration of treatment was 19
      days, with mortality rate of 55%. In 60% dysfunction of 4 or more organs was
      diagnosed. In 55% the underlying disease was surgical and abdominal cavity was
      the primary infection site (47%). Pathogens most likely to cause severe sepsis
      were G- (48%) and G+ (43%) bacteria, as well as fungi (21%). Positive blood
      culture was obtained in 45% of patients. Treatment involved antibiotic and
      support of organ function. Activated protein C was used in 8.2%, causing a
      reduction of mortality. CONCLUSIONS: Severe sepsis in Polish ICUs develops most
      frequently in the course of intra-abdominal infections. Dysfunction of 4 or more
      organs caused observed high mortality (55%) Internet surveillance proved to be
      useful method of collecting information, widely accepted by personnel of ICUs.

PMID- 15507857
TI  - Idiopathic portal hypertension: a case report.
AB  - BACKGROUND: Idiopathic portal hypertension (IPH) is diagnosed in patients with
      clinical symptoms of portal hypertension, patent portal vein, and the absence of
      morphological signs of liver cirrhosis, or when no other reason can be found for
      liver disease. IPH refers to a number of vaguely defined histological entities
      including idiopathic portal hypertension, incomplete septal cirrhosis, focal
      regenerative hyperplasia, and partial nodular transformation. These entities most
      likely belong to the spectrum of one disease, originating from the impairment of
      intrahepatic circulation. CASE REPORT: A young male patient was admitted to
      hospital due to splenomegaly, thrombocytopenia and leucopenia. One year earlier
      the patient had undergone transjugular intrahepatic portocaval shunt (TIPS) due
      to symptoms of portal hypertension, but without effect. Liver biopsy disclosed
      increased fibrosis of portal areas with the penetration of a few thin streaks of
      connective tissue into liver parenchyma, and isolation of single nodules just
      under the liver capsule. There were also discrete vascular changes. Liver
      cirrhosis was ruled out. The patient underwent splenectomy. The spleen manifested
      only signs of passive hyperemia. In the follow-up 6 months after surgery there
      was a marked improvement of the patient's general status and normal thrombocyte
      level. CONCLUSIONS: Splenomegaly may be the main symptom of IPH without liver
      cirrhosis. Histopathological assessment of liver biopsy can exclude liver
      cirrhosis, which has major consequences for treatment. In such patients
      splenectomy is usually sufficient, without the need for liver transplantation.

PMID- 15507858
TI  - Urinary tract infection caused by Aerococcus viridans, a case report.
AB  - BACKGROUND: Aerococcus viridans organisms are gram-positive, usually airborne
      cocci that are widely distributed in hospital environments. These bacteria have
      infrequently been encountered as a human pathogen causing bacteremia,
      endocarditis and urinary tract infections. The clinical significance of these
      bacteria may be overlooked due to their fastidious growth and often confused with
      other strains of streptococci. CASE REPORT: We report a case of urinary tract
      infection with bacteremia caused by A. viridans in an 87 year-old male nursing
      home resident. The patient presented with a fever of 103 degrees F, dysuria,
      hematuria and weakness for three days. Urinalysis showed large amount of blood,
      more than one hundred white cells/HPF and 4+ bacteria. Laboratory tests revealed,
      white blood cell count of 2300/cu mm (neutrophils 80%, bands 7%, lymphocytes 11%
      and monocytes 2%), hemoglobin 15.4 gm/dL, blood urea nitrogen 23 mg/dL and
      creatinine 1.2 mg/dL. Urine culture yielded growth of 10(5) CFU of A. viridans.
      The patient was treated for ten days with levofloxacin (both IV + PO).
      CONCLUSIONS: To date, no clinical case report of this nature has been described
      implicating A. viridans in urinary tract infections. Increased awareness and more
      studies of this genus should lead to the identification of their potential role
      in human infections.

PMID- 15507859
TI  - Hyperlipidemia-lower targets, greater challenges.

PMID- 15507860
TI  - Probiotic therapy: a real tool to reduce intestinal infections?

PMID- 15507861
TI  - Metabolic rate monitoring and energy expenditure prediction using a novel
      actigraphy method.
AB  - BACKGROUND: A novel actigraphy method, the proportional integral mode, was used
      for monitoring metabolic rate and energy expenditure during different levels of
      exercise intensity. MATERIAL/METHODS: 13 young (24+/-3 yrs) male subjects,
      clothed in T-shirts, shorts and athletic shoes, ran/walked for 30 min on a level
      treadmill at different speeds (3, 5, 2, 6, 4, and 7 mph), 5 min at each speed.
      The following variables were continuously measured: Actigraphy (PCD, USA) data at
      three different modes (proportional integral mode, zero crossing, and time above
      threshold) from the wrist; oxygen consumption (Sensor Medics, USA), and heart
      rate (Polar, Finland). RESULTS: Analysis of the measured data revealed with low
      correlation between oxygen consumption and zero crossing or time above threshold
      (R=0.364 and 0.384, respectively), but with high correlation between oxygen
      consumption and proportional integral mode (R=0.843). CONCLUSIONS: The
      proportional integral mode, which is unlike the other modes, followed the oxygen
      consumption and the heart rate curves, showing a potential unique method to
      predict oxygen consumption and energy expenditure.

PMID- 15507862
TI  - ADC mapping of normal human brain.
AB  - BACKGROUND: The quantification of diffusion conditions in normal human brain has
      been gaining more and more attention since diffusion weighted imaging (DWI) was
      proved to be an important tool in the evaluation of cerebral pathologies,
      especially regarding the diagnosis of hyperacute stroke. The purpose of this
      study was to investigate the apparent diffusion coefficient (ADC) and anisotropy
      index (AI) in normal human brain to evaluate physiological ADC values for an ADC
      mapping of different brain regions. MATERIAL/METHODS: 22 regions of interest
      (ROIs) in the ADC maps of 53 volunteers showing no cerebral pathologies were
      measured in the gray and white matter of the frontal, parietal and occipital
      lobes, the corpus callosum, and the lateral ventricles. RESULTS: Apparent
      diffusion is quite inhomogeneous for different brain regions. In both subcortical
      white matter (ADC: 525 x 10(-8) mm2/s, AI: 0.05) and in gray matter (ADC: 1486 x
      10(-8) mm2/s, AI: 0.05) diffusion was isotropic, while in periventricular white
      matter (ADC: 408 x 10(-8) mm2/s, AI: 0.34) and the corpus callosum (ADC: 799 x
      10(-8) mm2/s, AI: 0.77) anisotropic. CONCLUSIONS: With the exception of children
      and young adults, ADC seems to be intra- and interindividually constant, with no
      sex or age dependency for the patient sample we investigated (mean age: 62+/-9.4
      years). Hence the measurement of ADC may provide an index of lesion severity.

PMID- 15507863
TI  - Ceftriaxone monotherapy for the treatment of febrile neutropenia in patients with
      solid tumors: a prospective study of 100 episodes.
AB  - BACKGROUND: Broad-spectrum beta-lactam is the standard therapy for febrile
      neutropenia (FN) in cancer patients. The aim of our study was to evaluate the
      treatment of FN by a once-daily administration of ceftriaxone (CFX) alone.
      MATERIAL/METHODS: From Jan. 1, 1997 to Dec. 31, 2001 we prospectively analyzed
      100 episodes of FN in 94 patients. Inclusion criteria were: fever > or = 38.5
      degrees C, neutrophil count (NC) <500/microl, presumed short duration (<7 days),
      and no antimicrobial treatment within the preceding 72 h. Treatment consisted of
      2 g daily intravenous CFX alone until NC>500. Success criteria were: afebrile
      within 48 hours under CFX alone and without secondary infection. RESULTS: Twenty
      seven episodes occurred in patients with performance status (PS)>2. The median
      duration of neutropenia was 3.5 days (range 1-22). Etiology of fever was: 75 of
      unknown origin (FUO), 6 clinically defined (CDI), and 19 microbiologically
      documented (MDI). Median CFX treatment duration was 5 days. Successful response
      was obtained in 87% of cases; no deaths occurred. Treatment efficacy differed
      between FUO, CDI, and MDI with, respectively, 92.0, 83.3, and 68.4% success rates
      (p=0.042). Treatment failure was mostly observed in patients with PS > or = 2
      (p=0.0001). Among the 13 failures, 4 resolved in less than 4 days with CFX alone
      and 9 required additional or modified antimicrobial treatment. CONCLUSIONS:
      Considering the marked practical advantages of CFX alone (well-tolerated
      treatment with minimum side effects, once-daily administration, low cost, and
      high response rates), this single-agent regimen appears to be a valuable option
      in treatment of FN in patients with solid tumors.

PMID- 15507864
TI  - Low-dose balsalazide plus a high-potency probiotic preparation is more effective
      than balsalazide alone or mesalazine in the treatment of acute mild-to-moderate
      ulcerative colitis.
AB  - BACKGROUND: Balsalazide is well tolerated and effective in treating acute
      ulcerative colitis. VSL#3 is a probiotic cocktail proven to be effective in
      preventing flare-ups of chronic pouchitis. We compared the efficacy and safety of
      low-dose balsalazide (2.25 g/day) plus 3 g/day VLS#3 (group A) with medium-dose
      balsalazide alone (group B) and with mesalazine (group C) in the treatment of
      mild-to-moderate active ulcerative colitis. MATERIAL/METHODS: Ninety patients (30
      per group) were randomly enrolled, with a treatment duration of 8 weeks. Efficacy
      was assessed by symptoms assessment, endoscopic appearance, and histological
      evaluation. RESULTS: Balsalazide/VSL#3 was significantly superior to balsalazide
      alone and to mesalazine in obtaining remission: 24 patients of group A were in
      remission [per-protocol: 85.71% (C.I.95%: 62-96), on intention-to-treat: 80%
      (C.I.95%: 59-91)], while 21 group B [per-protocol: 80.77% (C.I. 95%: 51-82), on
      intention-to-treat: 77% (C.I.95%: 43-81)] and 16 group C patients [per-protocol:
      72.73% (C.I. 95%: 30-75), on intention-to-treat: 53.33% (C.I.95%: 42-62)] were in
      remission (p<0.02). Balsalazide with or without VSL#3 was better tolerated than
      mesalazine: two group C patients were withdrawn from the study because of severe
      side-effects; 1 group A (3.33%), 3 group B (10%) and 4 group C (13.33%) patients
      experienced slight side-effects. The balsalazide/VSL#3 combination was faster in
      obtaining remission than balsalazide alone or mesalazine (4, 7.5, and 13 days in
      groups A, B and C, respectively) and also better in improving all parameters
      evaluated. CONCLUSIONS: Balsalazide/VSL#3 may be a very good choice in the
      treatment of active mild-to-moderate active ulcerative colitis instead of
      balsalazide alone or mesalazine.

PMID- 15507865
TI  - Reviewing the mechanism of action of thiopurine drugs: towards a new paradigm in
      clinical practice.
AB  - The precise mechanism of action of thiopurine drugs remains unclear despite more
      than 40 years of use. Recent knowledge in the field of apoptosis and a better
      insight into, as well as a rapid increase in their use in several important areas
      of clinical medicine justify this appraisal. This is a review of the recent
      advances in the knowledge of their mechanism of action and is primarily intended
      to help clinicians understand the pharmacological properties of these drugs
      adequately and to find ways to improve their use in clinical practice. The parent
      compound is azathioprine (AZA), which is rapidly reduced in the presence of
      glutathione to 6-mercaptopurine (6-MP) and then metabolized into active
      metabolites with immune-modifier activity. Recent observations and new data
      indicate that AZA/6-MP could be considered as a "two-in-one" drug, providing a
      source of 6-thioguanine nucleotides (6-TGNs) and methylated metabolites, and that
      both compounds could contribute to its antiproliferative effects. This review
      will also focus on mechanisms that may help to explain a number of recent
      observations showing that myelotoxicity may occur in patients with high TPMT
      level or low 6-TGN rate. Our final proposal suggests that the immunosuppressive
      effects of these drugs are due to a balanced combination of antimetabolic and pro
      apoptotic actions.

PMID- 15507866
TI  - Atherosclerosis: immunopathogenesis and immunotherapy.
AB  - Atherosclerosis is a chronic disease that causes various cardiovascular
      complications. Although the initiation and progression of atherosclerosis largely
      depend on genetic factors and life styles, the cellular and molecular mechanisms
      are still not clear. Recent studies have revealed that cellular and humoral
      immunity plays crucial roles in atherogenic lesion formation, including
      macrophages, CD4+ and CD8+ T cells and dendritic cells as well as autoantigens
      such as heat shock protein (HSP 60/65) and oxidized LDL. Furthermore,
      atherosclerosis is associated with microbial or viral infection. Given these
      recent advances, various modifications of the immune system in mouse models have
      been performed to determine the underlying mechanisms of atherogenesis and new
      therapeutic strategies. Blocking of macrophage inducing factors or disruption of
      scavenger receptors on macrophages such as SR-A and CD36 can inhibit
      atherosclerosis progression. Switching the immune system of CD4+ T cells from Th1
      to Th2 can induce secretion of anti-inflammatory cytokine IL-10, leading to
      decreased atherosclerotic lesions. Eradication of microbes and viruses can also
      reduce atherosclerosis. These investigations strongly support that immune
      responses are important mechanisms of atherogenesis, and immunomodulation can be
      a new strategy to treat atherosclerosis.

PMID- 15507867
TI  - Habenular and interpeduncularis nuclei: shared components in multiple-function
      networks.
AB  - This paper reviews habenula (Hb) and interpeduncularis nucleus (IPN) literature
      from the perspective that the axial anatomy of Hb-IPN could be shared by numerous
      brain circuits that subserve diverse functions. The first section summarizes the
      major anatomical connections, showing that the axis is strategically positioned
      between key rostral structures and brainstem areas. Little is known about these
      connections as they relate to the heterogeneous Hb-IPN sub-nuclei. Insufficient
      understanding exists about ascending pathways in the fasiculus retroflexus,
      possible pineal gland connections with the Hb, serotonergic inputs, whether given
      pathways are excitatory or inhibitory, and interactions of neurotransmitter
      systems. Next reviewed are studies that implicate the Hb-IPN axis in a variety of
      brain functions and behaviors. These include nociception, learning and memory,
      motor activity, sexual and maternal behavior, stress, affective states (anxiety,
      depression, and reward phenomena), sleep, and eating and drinking behavior. I
      propose that these multiple functions arise because the Hb-IPN is a shared
      component axis in the multiple circuits that subserve these different elements of
      behavior. More research is needed to test the possibility that the Hb-IPN
      provides a way for the brain to share circuitry, to explore the significance of
      the anatomical convergence of inputs to the lateral Hb, to map the circuitry of
      the subnuclei in Hb and IPN, to explore the interactions of the multiple
      neurotransmitter systems involved, to conduct studies in simpler animals, and to
      design experiments that will elucidate system properties of circuits that share
      the Hb-IPN axis.

PMID- 15507868
TI  - Transgenic animals in medicine: integration and expression of foreign genes,
      theoretical and applied aspects.
AB  - The production of different pharmaceutically important human proteins in the
      mammary gland of transgenic animals constitutes an important field of modern
      biotechnology. In addition, transgenic animals are used to develop suitable
      models of various human diseases and the possibility of using transgenic
      technologies to adapt pigs for xenotransplantation of their organs to humans is
      widely discussed. All these practical applications depend on the availability of
      reliable techniques to obtain transgenic animals with the necessary spectrum of
      transgene(s) expression. In the present review we discuss different aspects of
      producing transgenic animals by microinjection procedure, including both
      technical aspects and theoretical issues. As far as the technical aspects are
      concerned, special emphasis is placed on DNA preparation, microinjection timing,
      vectors permitting delivery of large genomic fragments, and approaches used to
      increase integration frequency. The molecular basis of the advantage of transgene
      microinjection into a male pronucleus is discussed. Finally, different strategies
      used to obtain polytransgenic animals are critically reviewed. In the section
      devoted to theoretical issues, the mechanisms of integration and molecular
      systems regulating transgene expression are extensively discussed. In particular,
      the importance of the domain-level regulatory systems is outlined and
      experimental approaches permitting the use of the domain-level regulatory systems
      of the genes encoding milk proteins are described and discussed.

PMID- 15507869
TI  - Access to electronic health records in primary care-a survey of patients' views.
AB  - BACKGROUND: The NHS is moving towards electronic access to health records for
      patients from 2004 and needs to involve patients in the development process. The
      aim of the study was to explore the views of a large sample of patients about
      online access to EPRs and health information in primary care. Areas covered
      included: accuracy rights of access; security; confidentiality and smart cards.
      MATERIAL/METHODS: The questionnaire was sent to 1050 patients selected at random
      from the practice list after stratification for age and sex. RESULTS: 66% of
      patients aged over 20 years old responded. Patients know they have the right to
      see their records although few have done so. Overall they feel the advantages of
      electronic health records outweigh the disadvantages. They have concerns about
      security, confidentiality, understanding their records, their accuracy and
      completeness. The patients recognised the potential benefits to their healthcare
      and relationships with health professionals. There was a majority view that
      parents / guardians and carers should have access to their dependants' records.
      CONCLUSIONS: Patients need to be confident that access is limited to those who
      have the right to see the records. The majority were confident they would
      understand their records and about half were familiar with computer use. However
      these are major issues for older patients who will require assistance in order to
      benefit from accessing their EPRs. It is essential that patient involvement takes
      place at every stage of the development of EPRs and that their views are taken
      into account.

PMID- 15507870
TI  - Ludwik Hirszfeld Memorial Lecture: HIV-1 reservoirs: major molecular obstacles to
      viral eradication.
AB  - Over the last 18 years of study in one of our laboratories, we have observed the
      development of residual disease and latent reservoirs as major problems in the
      long-term therapy of HIV-1-infected individuals on highly active antiretroviral
      therapy (HAART). It was shown in the early 1990 's that HAART, as it is presently
      configured, is unlikely to lead to viral eradication due to several mechanisms of
      viral persistence. The two general mechanisms involved with persistence during
      HAART include low-level residual, cryptic replication and proviral latently
      infected cells. As such, these are key areas of potential studyfor depletion and,
      hopefully in the future, eradication of residual disease in patients on
      suppressive HAART. To deplete these residual disease mechanisms will require
      multipronged approaches. These will include induction of HIV-1 latent proviruses,
      suppression of residual viral replication and destruction of long-lived cellular
      sanctuaries, such astissue-bound macrophages.

PMID- 15507871
TI  - Nucleic acid aptamers in human viral disease.
AB  - Nucleic acid aptamers are short, single-stranded oligonucleotides or their
      modified analogues which avidly and specifically interact with targeted ligands
      through their 3-dimensional structure. Aptamers can be selected out of a large
      combinatorial oligonucleotide library through an in vitro evolution process
      termed SELEX. Since 1990, a wide variety of aptamers targeted to ligands ranging
      from small molecules to complex mixtures have been isolated. Most selected
      aptamers have shown high specificity to and affinity for their ligands and are
      potential detection and/or diagnostic reagents. Furthermore, some aptamers
      specifically inhibit biological functions of targeted proteins, resulting in
      potent therapeutic candidates in disease models. Some recent advances to increase
      the stability of aptamers, extend their in vivo circulation time and their in
      vivo expression have pushed aptamers closer to therapeutic applications. This
      review presents recent developments in the field of aptamer research and focuses
      on their applications to human viral diseases, particularly HIV induced diseases.

PMID- 15507872
TI  - Genetics of experimental autoimmune encephalomyelitis in the mouse.
AB  - Multiple sclerosis (MS) is an inflammatory, demyelinating disease in the central
      nervous system (CNS) affecting approximately 0.1% of the population in the
      northern part of the world. The factors behind the initiation of the inflammatory
      response are not known at present, but MS is considered as a complex disease
      depending on genetic as well as environmental factors. Experimental autoimmune
      encephalomyelitis (EAE) is the prevailing experimental rodent model for multiple
      sclerosis (MS). Disease is induced in genetically susceptible mice or rats by
      immunization with myelin proteins or peptides, which leads to an infiltration of
      leukocytes into the CNS. EAE has been subjected to investigations of genetic
      susceptibility to disease development. By the identification of genes
      predisposing to EAE, the hope is to get clues as to what genetic elements are
      also important in MS. To date, more than 25 Eae loci have been described in the
      mouse. The quantitative trait loci are linked to different disease traits and
      several show sex specificity. Here we discuss the current state of the genetics
      controlling susceptibility to EAE.

PMID- 15507873
TI  - Protein catabolism in chronic uremia: is it due to malnutrition?
AB  - The high prevalence of anthropometric measurements and laboratory values that are
      similar to those in patients with protein-energy malnutrition has lead to the
      classification of a large number of dialysis patients as being malnourished.
      However, malnutrition in the strict sense implies that abnormalities will be
      reversed if more food is eaten. There is virtually no evidence, however, that
      simply providing more nutrients in the diet of dialysis patients will reverse the
      abnormalities attributed to malnutrition. This suggests that the diagnosis of
      malnutrition is a misdiagnosis. In this review, we discuss mechanisms that will
      cause the loss of protein stores, including albumin, other plasma proteins, and
      muscle mass in dialysis patients. We will also review the shortcomings of
      techniques that are used to measure the nutritional status of these patients.

PMID- 15507874
TI  - New target against inflammatory diseases: transglutaminase 2.
AB  - Transglutaminase (TGase)2 is an enzyme that is widely used in many biological
      systems for generic tissue stabilization or immediate defense for wounds. Many
      reports showed that TGase 2 is aberrantly activated in tissues and cells and
      contributes to a variety of diseases, including neurodegenerative diseases and
      autoimmune diseases. In most cases, TGase 2 appears to be a factor in the
      formation of inappropriate proteinaceous aggregates that may be cytotoxic.
      However, in other cases, such as celiac disease, arthritis, lupus, and
      amyotrophic lateral sclerosis, TGase 2 is involved in the generation of
      autoantibodies. This suggests the possibility that inappropriate expression
      and/or presentation of TGase 2 to T cells might contribute to these diseases in
      genetically predisposed individuals. We and others have found that TGase 2
      expression is also increased in the inflammation process. Furthermore, we also
      demonstrated a reversal of inflammation by Tgase inhibition. This review will
      examine a possibility of TGase inhibitors as therapeutic agents in a variety of
      inflammatory diseases.

PMID- 15507875
TI  - Neurokinin receptors: relevance to the emerging immune system.
AB  - The adult bone marrow (BM )is the major site of the emerging immune system.
      Hematopoiesis is the process whereby immune cells are generated from a finite
      number of hematopoietic stem cells. Hematopoiesis is regulated by soluble
      mediators and inter cellular interactions. A major regulatory mechanism of
      hematopoiesis involves bidirectional crosstalk with the neural system. This
      communication mainly occurs by the release of neurotransmitters from innervated
      fibers. The neurotransmitters interact with specific receptors on BM resident
      cells and release other hematopoietic regulators such as cytokines. Together, the
      neurotransmitters and cytokines form a complex network to regulate hematopoiesis.
      Among BM resident cells, the stromal cells are particularly relevant for two
      reasons:1) they represent non-neural sources of neurotransmitters, and 2) stromal
      cells express specific receptors for neurotransmitters. This review focuses on
      the hematopoietic effects of neurotransmitters belonging to the tachykinins. The
      two major tachykinins focused in this review are substance P and neurokinin (NK)
      A,11 and 10 amino acid peptides. In BM, the tachykinins interact with two major
      NK receptors:NK-1 and NK-2. These two receptors appear to limit tachykinin
      mediated effects on hematopoiesis. The central roles of NK receptors within a
      network comprising of cytokines and tachykinins are reviewed.

PMID- 15507876
TI  - beta(3)-Integrin cytoplasmic binding proteins.
AB  - Integrins are cell-surface adhesion receptors that play an important role in
      mediating numerous physiological processes,including inflammation, migration,
      adhesion, and proliferation. Integrin regulation by events within the cell has
      been termed "inside-out " signaling; this is a capacity that is unique to
      integrin receptors. As is typical of other cell-surface receptors, integrins can
      also transduce signals from outside the cell into the cytoplasm on binding
      extracellular ligands ("outside-in signaling "). Integrins are composed of an
      alpha and a beta subunit, which form a heterodimer. The beta(3)-integrin family
      consists of alpha(IIb)beta(3)-found on platelets and megakaryocytes, and the more
      widely distributed alpha(v)beta(3). beta Subunits consist of a large
      extracellular domain, a single transmembrane segment, and a relatively short
      cytoplasmic tail. The cytoplasmic domains do not contain intrinsic tyrosine
      kinase activity, and therefore signaling occurs primarily via recruitment of
      intracellular signaling molecules. Integrins form transmembrane connections, and
      the interactions between integrin cytoplasmic domains, intracellular factors
      (cytoplasmic proteins and intracellular signaling pathways), and membrane
      anchored proteins play an important role in integrin-mediated events. There are
      at least 21 proteins that associate with integrin beta tails to regulate cell
      motility, proliferation, differentiation, and apoptosis. In this review, we will
      focus on 10 of these proteins and their function in integrin-mediated events.

PMID- 15507877
TI  - Treatment options for severe lupus nephritis.
AB  - Renal involvement in systemic lupus erythematosus is a common complication that
      significantly worsens morbidity and mortality. Landmark trials conducted by the
      National Institutes of Health established cyclophosphamide as the mainstay of
      therapy. Since then, the prognosis of patients with lupus nephritis has markedly
      improved, and 10-year survival rates now surpass 75%. These superior outcomes
      have come at the expense of adverse events such as serious infections and gonadal
      failure in a significant number of patients,and the relapsing nature of the
      disease continues to pose a problem. For thesereasons, new treatment protocols,
      such as mycophenolate mofetil induction or sequential therapies using
      azathioprine or mycophenolate mofetil in the maintenance phase, have been
      developed in recent years with the goal to maintain remission and reduce adverse
      events. In addition, ongoing research into the pathogenesis of lupus nephritis
      has confirmed the importance of B and T cell activation, leading to the
      identification of potential new therapeutic targets. This article discusses
      established and novel treatment options for patients with severe lupus nephritis
      corresponding to WHO classes III, IV, and V withIII or V with IV.

PMID- 15507878
TI  - CTLA-4 (CD152) gene polymorphism at position 49 in exon 1 in Graves' disease in a
      Polish population of the Lower Silesian region.
AB  - INTRODUCTION: Graves' disease ((GD)is an autoimmune disease believed to be caused
      by a combination of environmental and genetic factors. The gene encoding
      cytotoxic T lymphocyte-associated antigen-4 (CTLA-4)is one of the candidate genes
      for conferring susceptibility to thyroid autoimmunity. he aim of the study was to
      investigate the association between the exon 1 CTLA-4 gene polymorphism A(49)G
      and susceptibility to GD and Graves ' ophthalmopathy (GO)as well as its severity
      in a Polish population of the Lower Silesia region. MATERIALS AND METHODS: We
      analyzed the A(49)G exon 1 CTLA-4 gene polymorphism in 99 unrelated Polish
      patients with GD, of whom 50 had clinically evident GO (NOSPECS class III and
      higher), and 154 matched healthy subjects from the Lower Silesia region. Genomic
      DNA was isolated from whole frozen blood using the NucleoSpin Blood kit. A/G
      transition was genotyped by polymerase chain reaction followed by labeling with
      the SnaPshot kit of PE Applied Biosystems and detected using an ABI PRISM 310
      capillary genetic analyzer. RESULTS: The distribution of CTLA-4 exon 1 A(49)G
      enotype, allele, and phenotypic frequencies did not differ between patients with
      GD and healthy subjects. There was a significantly lower frequency of the AA
      genotype in the group of patients with clinically evident GO than in patients
      without severe GO (22% vs. 43%; p=0.02, OR=2.6). CONCLUSIONS: Our results showed
      that the AA genotype in patients with GD is associated with a lower risk of GO
      severity.

PMID- 15507879
TI  - Risk factors for asthma incidence. A review of recent prospective evidence.
AB  - AIM: The aim of this study is to determine what factors have been shown, in
      prospective studies, to predict the incidence of asthma. METHODS: We performed a
      systematic review of peer-reviewed literature from 1994 to 2004 to determine what
      factors predict the development of asthma in both children and adults. This
      search strategy yielded 40 studies, with 36 providing some estimate of asthma
      incidence for the total sample and or a specific subgroup. RESULTS: Annual
      estimated incidence of physician-diagnosed asthma ranged from 0.6 to 29.5 per
      1000 persons. Risk factors for incident asthma among children included: male sex,
      atopic sensitization, parental history of asthma, early-life stressors and
      infections, obesity, and exposure to indoor allergens, tobacco smoke and outdoor
      pollutants. Risk factors for adult-onset asthma included female sex, airway
      hyperresponsiveness, lifestyle factors, and work-related exposures. CONCLUSION:
      Risk factors for asthma include both modifiable and nonmodifiable ones, and they
      vary between children and adults. This review of prospective evidence supports
      tobacco and smoke avoidance as an intervention for the primary prevention of
      childhood asthma. During adolescence and adulthood, targeting lifestyle factors
      like obesity and smoking or reducing occupational exposures are the best
      opportunities for asthma prevention. Before specific public health
      recommendations can be made, however, additional longitudinal research is needed
      to better characterize target populations and identify appropriate settings for
      multifaceted asthma interventions.

PMID- 15507880
TI  - Clinical aspects of occupational asthma.
AB  - In about 1 in 10 cases, new or recurrent asthma in adulthood will be caused by
      work. In many cases the asthma will arise from the action of non-specific airway
      irritants on a background of bronchial hyperreactivity; in others the mechanism
      is one of hypersensitivity to a specific agent for which the label ''occupational
      asthma'' is generally reserved. Some 300 different workplace agents are capable
      of inducing asthma but most cases are attributable to a far smaller number to
      which exposure is incurred in a few high-risk occupations. The clinical diagnosis
      of occupational asthma is usually straightforward; problems occur in patients
      with pre-existing asthma or in those with unusual exposures, especially if these
      are to low molecular weight agents. Management is more difficult since there are
      often important employment and other social issues to be taken into account.

PMID- 15507881
TI  - Genetic aspects of asthma.
AB  - Over the last few years, a significant progress has been made in understanding of
      the genetic basis of asthma. This has led to the identification of several
      chromosomal regions and loci showing linkage to and association with asthma and
      asthma-linked phenotypes. Recent positional cloning approaches have also been
      informative in identifying several strong candidate genes for asthma. The next
      challenge will involve validation of these findings and, importantly,
      identification of the functional basis in the pathophysiology of asthma. This
      review will describe the power of positional cloning for the identification of
      asthma genes, highlight the functional importance of the genetic variants, and
      address the gene-gene and gene-environment interactions that are pertinent to
      this challenging field.

PMID- 15507882
TI  - Gastro-oesophageal reflux disease and asthma: would be possible to improve
      therapy on the basis of what is now known?
AB  - Gastro-oesophageal reflux disease (GORD) is a chronic and relapsing clinical
      condition, associated or not to histopathologic alteration resulting from
      repeated contact of oesophageal mucosa with gastric content. This condition
      occurs with high prevalence in the general population and represents one of the
      most frequent reasons for health care-seeking addressed to primary care physician
      and gastroenterologists. A plethora of extra-oesophageal manifestations have been
      described in patients suffering from GORD and a causal relationship has been
      postulated by many investigators. A large cohort of studies has focused on the
      possible cause-effect interaction between GORD and asthma. However, despite the
      improvement in both asthma symptoms and medication requirements after anti
      secretory therapy, no change in pulmonary function is evident. Furthermore, the
      pathogenetic mechanism, a vagally mediated reflex, microaspiration or increasing
      reactivity to the stimuli, is yet unclear. Since conflicting conclusions and the
      failure to find a causal relationship are generally due to the heterogeneity of
      the studies, further research is needed to clarify the role of GORD in asthma
      pathogenesis, or viceversa, and whether a medical or surgical anti-secretory
      treatment may be an approach to curing the asthma patients non-responders to the
      classical therapy.

PMID- 15507883
TI  - Omalizumab: efficacy in allergic disease.
AB  - Asthma and allergic rhinitis are common conditions that have a substantial impact
      on patient quality of life, severely disrupting physical, emotional and social
      functioning. These diseases share many pathophysiological characteristics and
      recent research has provided evidence that a strong causal relationship exists
      between allergy and both asthma and allergic rhinitis. As a root cause of
      allergic diseases of the airways, immunoglobulin E (IgE) represents an
      appropriate target for the development of new therapies. Omalizumab (Xolair) is a
      recombinant humanized monoclonal anti-IgE antibody that has demonstrated efficacy
      in allergic asthma and other IgE-related allergic illnesses. In three pivotal,
      placebo-controlled trials in patients with moderate-to-severe allergic asthma,
      omalizumab provided effective disease control, significantly reducing
      exacerbations while improving quality of life. Additionally, omalizumab reduced
      the need for unscheduled outpatient visits, emergency room visits and
      hospitalizations. Omalizumab was particularly useful as add-on treatment for
      patients with poorly controlled severe asthma. Similar benefits were reported in
      patients with seasonal or perennial allergic rhinitis. Omalizumab significantly
      improved disease symptoms and reduced the use of rescue antihistamines. In
      patients with concomitant asthma and perennial allergic rhinitis, omaliuzumab
      significantly prevented asthma exacerbations and improved quality of life
      compared with placebo. Taken together, these results suggest that omalizumab
      represents an important clinical advance in the management of allergic disease.

PMID- 15507884
TI  - The value of a logbook for young vascular surgeons in training The UEMS
      experience.

PMID- 15507885
TI  - Effects of defibrotide in patients with chronic deep insufficiency. The PROVEDIS
      study.
AB  - AIM: In the present study the effect of defibrotide, an antithrombotic and
      profibrinolytic agent, was investigated in patients with chronic venous
      insufficiency (CVI) due to deep vein obstruction and/or reflux (chronic deep vein
      insufficiency, CDVI). METHODS: The study was a multicenter, randomized, double
      blind placebo controlled trial in which only patients with CDVI confirmed by
      ultrasound were enrolled. All patients were treated with adequate elastic
      compression and randomized to receive either oral defibrotide (800 mg/die) or
      matching placebo for 1 year. Patients with active or previous leg ulcer were
      excluded. RESULTS: A total of 288 patients were randomized and 159 completed the
      study. At baseline ultrasound investigation, obstructive changes were found in
      2/3 of all patients thus ascertaining a post-thrombotic syndrome (PTS). The
      primary endpoint, ankle circumference, was significantly reduced under
      defibrotide from day 120 throughout 360. Scores for pain and edema were improved.
      The number of episodes of superficial thrombophlebitis and deep vein thrombosis
      was significantly lower under defibrotide (n=2) than under placebo (n=10). The
      majority of these events occurred in the subset of patients with documented PTS.
      CONCLUSION: Treatment with defibrotide in addition to elastic compression in
      patients with objectively assessed CDVI, mostly due to PTS, resulted in clinical
      benefits and prevented thrombotic complications harmful to the limb conditions.

PMID- 15507886
TI  - Economic evaluation of a short-course intensive rehabilitation program in
      patients with intermittent claudication.
AB  - AIM: The aim of this study was to provide cost-description and cost-effectiveness
      of a short-course intensive in-hospital rehabilitation program in patients with
      intermittent claudication. METHODS: Costs per case treated were calculated
      according to a local standard protocol including diagnostic evaluation of
      peripheral arterial disease and other related cardiovascular conditions, physical
      training, and secondary prevention. Three additional less structured scenarios
      were also evaluated. RESULTS: All 107 enrolled patients (males 91%, mean age 65+/
      8 years) completed the program (4-week duration; twice a day walking exercise)
      and showed significant increases in walking performance, as evaluated by constant
      treadmill-test. At admission, the mean values of initial claudication distance
      (ICD) and absolute claudication distance (ACD) were 150+/-111 and 432+/-327 m,
      respectively. At the end of the program, 12 (11%) patients completed the
      treadmill test without pain, while 31 (29%) completed the test without stopping
      due to maximal pain. Among the remaining 64 (60%) patients, the ICD and ACD
      increased by 137% and 112%, respectively. The cost per case treated ranged from
      Euro 1733.2 (standard protocol) to Euro 918.9 (physical training only). By adding
      the cost of hospitalization and indirect costs, the same costs ranged from Euro
      4626.2 to Euro 3811.9. The average cost to walk one additional meter without pain
      as a result of the rehabilitation program was Euro 57.5, while the cost to walk
      one additional meter before stopping was Euro 27. As showed by sensitivity
      analysis, the maintenance of the expected level of treatment success was crucial
      for program's cost-effectiveness. CONCLUSION: From the societal viewpoint, short
      course intensive rehabilitation may be cost-effective in patients with stable
      intermittent claudication and could be considered in decision models evaluating
      different therapeutic options.

PMID- 15507887
TI  - Reproducibility of proximal and distal transcutaneous oxygen pressure
      measurements during exercise in stage 2 arterial claudication.
AB  - AIM: Although transcutaneous oxygen pressure measurements (tcpO2) are largely
      used in the investigation of vascular patients, its reproducibility is still
      debated. Indeed an unpredictable gradient exists between arterial and
      transcutaneous oxygen pressure. We hypothesised that indices taking into account
      changes over time and independent of absolute starting values would be more
      reproducible than other indices. METHODS:  EXPERIMENTAL DESIGN: comparative test
      retest procedure (1 to 13 days between tests). SETTINGS: institutional practice,
      ambulatory care. PATIENTS AND PARTICIPANTS: 15 subjects with stage 2
      claudication. INTERVENTIONS: tcpO2 recordings at rest and at exercise during the
      2 treadmill tests. MEASURES: calculation of the Delta-from-rest of oxygen
      pressure index (limb tcpO2 changes minus chest tcpO2 changes), of the resting -
      or minimal values attained during exercise - of absolute tcpO2 and of the
      regional perfusion index (regional perfusion index: ration of limb to chest).
      RESULTS: Both absolute tcpO2 and regional perfusion index at rest showed low
      reproducibility. During exercise the best reproducibility was attained through
      Delta-from-rest of oxygen pressure index calculation. Equations from the linear
      regression analysis (test 2 versus test 1) were 0.88 x -4.2 (r(2)=0.82) at the
      buttock level and 0.82 x -3.8 (r(2)=0.80) at the calf level. CONCLUSION: TcpO2
      measurement on the calf or buttock during exercise, is a reproducible measurement
      in patients with vascular claudication, specifically when corrected for exercise
      induced systemic pO2 changes trough Delta-from-rest of oxygen pressure
      calculation.

PMID- 15507888
TI  - White blood cell and endothelial cell response to endovascular procedures in the
      leg.
AB  - AIM: The longterm patency of endovascular procedures is partly depending on
      restenosis by intimal hyperplasia, a process depending on inflammatory mechanisms
      resembling the mechanisms of normal repair and the process of atherosclerosis.
      The aim of this study was to characterize the inflammatory response of white
      blood cells (WBC) and endothelial cells following endovascular procedures in the
      leg. METHODS: Venous blood samples were drawn from a cubital vein before and 2
      hours after intervention in 19 patients suffering from peripheral arterial
      occlusive disease (PAOD). Flow cytometry was used to identify and determine the
      concentrations of WBC and platelets and to measure CD11b/CD18 on WBC and CD41 on
      platelets. Soluble endothelial markers (sICAM-1, sE-selectin, sP-selectin and
      sVCAM-1) were measured by ELISA technique. RESULTS: WBC were downregulated
      following endovascular procedures. The endothelial cell response was limited and
      only downregulation of sP-selectin reached significant levels. The results were
      more evident in the group of patients with critical limb ischemia (CLI) compared
      to patients with intermittent claudication (IC). CONCLUSION: Endovascular
      procedures in the leg evoke only a limited response which is depending on the
      degree of ischemia and the magnitude of the interventional procedure.

PMID- 15507889
TI  - Elevated soluble cell adhesion molecules E-selectin and intercellular cell
      adhesion molecule-1 in type-2 diabetic patients with and without asymptomatic
      peripheral arterial disease.
AB  - AIM: Cell adhesion molecules may serve as markers of endothelial cell activation,
      and they may well have a role in the pathogenesis of atherosclerotic vascular
      disease in diabetes mellitus. METHODS:  EXPERIMENTAL DESIGN: a cross sectional,
      comparative study. SETTING: a teaching University Hospital. Patients and
      controls. A cohort of diabetic patients with absent peripheral arterial pulses
      but no history of cardiovascular or cerebrovascular disease i.e. asymptomatic
      (n=29), median age 68 (36-80) years, (range), diabetes duration 10 (1-43) years
      and HbA1c 7.7% (4.8-9.6). They were compared to 12 age and sex matched normal non
      diabetic controls. INTERVENTION: none. MEASURES: soluble cell adhesion molecules
      intercellular cell adhesion molecule-1 (ICAM-1) and E-selectin levels measured by
      ELISA methods. RESULTS: The 29 patients with diabetes, as a whole, were found to
      have significantly higher median plasma sICAM-1 and sE-selectin of 283 ng/ml (154
      1000) (range), and 65.8 ng/ml (20.6-145) vs 237 (147-312.4) and 37.7 (19.8-46.6)
      respectively, Mann Whitney U test p<0.02, and p<0.002. In the diabetic group, E
      selectin correlated with ICAM-1, age and HbA1c: r=0.524 p<0.01, r=0.385 p<0.05
      and r=0.393 p<0.05 respectively (Spearman correlation coefficient). CONCLUSION:
      These results confirm that elevated levels of adhesion molecules, E-selectin and
      ICAM-1 occur in Type-2 diabetes early in the course of asymptomatic peripheral
      arterial occlusive disease, and this is related to glycemic control. This
      suggests that adhesion molecules may have a role in the pathogenesis of
      atherosclerotic vascular disease in diabetes.

PMID- 15507890
TI  - Prevalence of lower limb occlusive vascular disease in outclinic diabetic
      patients.
AB  - AIM: The aim of this study was to determine the prevalence and risk factors for
      peripheral occlusive vascular disease (POVD) in subjects with diabetes mellitus
      (DM) in Brazil. METHODS: We evaluated 236 diabetic individuals, in spontaneous
      demand, representing 471 legs. POVD was assessed by the ankle brachial index
      (ABI). RESULTS: The mean age was 62.1 years (range 22-89 years), 52% were male,
      93.2% type II DM and the mean time to diagnosis was 7.9 years (range 0-37 years).
      Sixty percent were hypertensives. In 61% at least one pulse was diminished or
      absent. The prevalence of ischemia was 18% (ABI<0.9) while 22% had an ABI
      compatible with high grade arterial calcification (ABI>1.3). Overall less than
      1/3 of the cases had the vascular exam that could be considered normal. The ABI
      was lower in subjects with pulse deficit (p<0.001), and a normal pulse had a
      negative predictive value for ischemia of more than 90%. Subjects with normal
      pulses were younger and had a decreased diabetes duration (p<0.001 and p<0.05,
      respectively). An increase in the duration of the diabetes was associated with a
      progressive decrease in the ABI (p<0.01). Female gender and hypertension were
      associated with a reduced ABI (p<0.01 and p<0.05, respectively). CONCLUSION:
      There is a high prevalence of POVD in diabetic individuals. The disease is
      associated with hypertension and female gender and gets worse with increasing
      duration of the diabetes.

PMID- 15507891
TI  - Effects of acetylsalicylic acid on experimental atherogenesis induced in rabbits.
AB  - AIM: Inflammation related processes play a key role in the current etiologic
      model of atherosclerosis and its acute complications. In addition, platelet
      derived growth factors stimulate the neointimal proliferation of restenosis after
      coronary interventions. Reducing platelet accumulation at treated sites may
      attenuate restenosis. The purpose of this experimental study was to investigate
      the effect of acetylsalicylic acid (ASA), a widely used anti-platelet and anti
      inflammatory agent on the development and extent of atherosclerosis. METHODS:
      Fourty-eight male white New Zealand rabbits were separated in 4 groups (12
      animals each group). Group I received a diet of 2% cholesterol and 6% corn oil
      for 3 months. Group II received a diet of 2% cholesterol and 6% corn oil and in
      addition received 3 mg of ASA/kg daily intramuscular (i.m.) for 3 months. Group
      III received the same diet, and in addition received 10 mg of ASA/kg daily i.m.
      for 3 months. Group IV received the same diet and in addition received 50 mg of
      ASA/kg daily i.m. for 3 months. Animals were sacrificed after 3 months. RESULTS:
      ASA reduced the serum levels of total cholesterol, total lipids, triglycerides
      and LDL cholesterol. There was significant difference in the extent of
      atherosclerotic lesions between animals which received different doses of ASA and
      that animals which did not received any ASA. High dose ASA treatment resulted in
      an increase in fasting plasma glucose, associated with a reduction in total
      cholesterol and triglycerides. CONCLUSION: Our results suggest that there is a
      protective effect on atherosclerosis development of ASA down stream from where it
      lowers plasma fatty acid concentrations. However, further studies are required to
      verify that effect.

PMID- 15507892
TI  - Is carotid stenosis correlated with tympanosclerosis.
AB  - AIM: Tympanosclerosis and atherosclerosis seem to have a similar inflammatory
      origin despite the different tissues involved. We have investigated the possible
      relationship between tympanosclerosis and atherosclerosis by evaluating the
      incidence of tympanic plaques in patients with significant carotid disease.
      METHODS: Between September 1(st) 2002 and April 30th 2003, we have evaluated all
      patients undergoing carotid surgery for significant carotid stenosis (group A).
      If at least 1/5 of the eardrum was occupied by plaques, then the case was
      considered positive. A control group of patients of similar age and no history of
      otological nor vascular pathologies was enrolled (group B). The 2 groups were
      compared statistically by Fisher's test and significance was set at p=0.05.
      RESULTS: Group A consisted of 84 patients. In this group 32 patients (38.1%) had
      tympanosclerosis; it was bilateral in 12 cases. Group B had 84 patients. In this
      group tympanosclerosis was present in 11 cases (13%). The difference between the
      2 groups was statistically significant (p=0.005). CONCLUSION: More studies are
      needed before we can understand the cause of the association between these 2
      pathologies. However early screening of atherosclerotic disease in patients with
      tympanosclerosis seems justifiable on the basis of the data of both the
      literature and the present study.

PMID- 15507893
TI  - Chronic venous disease in the male. An epidemiological survey.
AB  - AIM: Chronic venous disease affects large numbers of men but there are fewer
      references to them than to women in the literature. The aim of our study was to
      determine the time lapse between the first symptom(s) and/or clinical signs of
      venous disease in the male and the first consultation with an angiologist to
      define the status of the veins within this population, and to demonstrate any
      possible links between the characteristics of the disorder in accordance with the
      CEAP international classification. METHODS: The design was a cross-sectional
      descriptive survey. Each physician had to include the first 3 patients examined
      for the first time. Each male patient had to present at least 1 sign and 1
      symptom of chronic venous disease. After randomization, 192 physicians included
      561 patients: 494 have been analyzed. RESULTS: The examined patients had a mean
      age of 49.3+/-13.7 years, mean height of 1.76+/-0.07 m, mean weight of 78.2+/
      11.2 kg and a BMI of 25.3+/-3.3. The disorder had been developing for a mean
      76.8+/-90.3 months prior to the specialist consultation. The longer the time span
      between the onset of the condition and the first consultation with a specialist,
      the more advanced was the condition as was also true with the increasing age of
      the patients. The following associations were observed: the incidence of trophic
      disorders increased with age (odds-ratio 1.47). The severity of the disease
      increased the greater the extent of obesity (odds-ratio 3.5). CONCLUSION: The
      risk of trophic disorders was higher in shop workers, craftsmen (odds-ratio 3.7)
      and workers (odds-ratio 2.68) than in executives, in those working in a standing
      position (odds-ratio 1.5), in those whose father had the condition (odds-ratio
      1.9), in the event of a popliteal reflux (odds-ratio 3.2) rather than affecting a
      saphenous trunk (small saphenous vein odds-ratio 2.5, great saphenous vein odds
      ratio 1.9). Thirty-two percent of patients with trophic disorders had already
      worn elastic compression prior to the specialist consultation. After this
      consultation, the numbers for whom this was prescribed rose to 87%.

PMID- 15507894
TI  - Epidemiology of chronic venous insufficiency of the lower limbs in the primary
      care setting.
AB  - AIM: The objective of the study was to describe the general characteristics, risk
      factors and clinical symptoms of patients seeking medical care at the primary
      care setting because of chronic venous insufficiency. METHODS: A total of 606
      general practitioners throughout Spain participated in this epidemiological,
      cross-sectional, multicenter study in which 6 695 patients were included. During
      a 3-month period, each participating physician filled out a questionnaire for all
      consecutive patients with venous leg complaints attended at his/her consultation.
      The following data were recorded: demographic features and anthropometric
      characteristics, level of physical activity, tobacco and/or alcohol consumption,
      number of pregnancies, other risk factors for chronic venous insufficiency,
      clinical manifestations, and signs on physical examination. RESULTS: Women
      accounted for 81.3% of the sample. Risk factors included tobacco smoking in 33.8%
      of cases, alcohol consumption in 25%, low physical activity in 55.7%, and family
      history in 47.2%. Patients recognized prolonged standing as the most frequent
      factor probably related to the origin of the symptoms (30.7%). Heaviness in the
      legs (84.8%) and itching (53.9%) were the most common symptoms, whereas ankle
      edema (43.6%) was the most frequent sign followed by telangiectases (37.6%). The
      presence of family history, a higher body mass index an age older than 45 years
      seems to be related with an increased frequency of clinical manifestations.
      CONCLUSION: Among patients seeking medical care because of chronic venous
      insufficiency, women seemed to ask for attention more frequently than men and the
      beginning of symptoms was mainly related to a prolonged orthostatic posture,
      being overweight the second cause stated. Heavy legs was the most frequent
      symptom followed by itching, and ankle edema was the most frequent sign.

PMID- 15507895
TI  - Matrix metalloproteinases in the vein wall.
AB  - AIM: Matrix metalloproteinases contribute to extracellular matrix remodelling
      that can influence mechanical properties of the vein wall and predispose to
      varicose veins development. The aim of the study was to assess the following
      matrix metalloproteinases in the wall of varicose veins: tissue collagenase I
      (MMP-1), gelatinase A (MMP-2), gelatinase B (MMP-9) and stromelysin 1 (MMP-3).
      METHODS: Normal, varicose and varicose veins complicated by thrombophlebitis were
      collected during the surgical treatment of 26 patients. In harvested tissues the
      presence of gelatinases was detected with zymography, contents of MMP-1, MMP-2,
      MMP-3 and MMP-9 were evaluated with ELISA, activity of MMP-1 was assessed with
      HPLC and activity of MMP-2 with ELISA. RESULTS: Zymography demonstrated
      particularly high contents of both gelatinases in the wall of varicose veins
      complicated by thrombophlebitis. The contents of MMP-1, MMP-2 and MMP-9 were
      significantly increased only in the wall of varicose veins complicated by
      thrombophlebitis, whereas the increased content of MMP-3 was also found in the
      wall of varicose veins. A significantly higher activity of MMP-1 was shown only
      in the wall of varicose veins complicated by thrombophlebitis, whereas an active
      form of MMP-2 was increased in the wall of varicose, as well as varicose veins
      complicated by thrombophlebitis, when compared with normal ones. CONCLUSION: The
      wall of varicose veins, particularly those complicated by thrombophlebitis shows
      extensive alterations in the content and activity of matrix metalloproteinases,
      that may result in extracellular matrix remodelling, influence mechanical
      properties of the vein wall and predispose to further progression of the disease.

PMID- 15507896
TI  - Long-term histopathologic evaluation of inferior vena cava after modified
      Greenfield filter implantation. Experimental study in sheep.
AB  - AIM: The authors assess a modified Greenfield filter (GF) for the long-term
      patency, filter tilting and histopathologic alterations of the inferior vena cava
      (IVC). METHODS: Adult sheep (n=7) underwent modified GF placement in the IVC.
      Cavograms were obtained every 3 months and pulmonary angiography at 12 months.
      Histopathologic and scanning electron microscopy (SEM) analyses were performed on
      the IVC explanted at 12 months. RESULTS: Cavograms showed that all IVC were
      patent at the end of the study. Filter tilting occurred in 2/7 animals and
      extrusion of struts was not observed. Macroscopic examination at explantation
      showed minimal venous wall thickening. Microscopic examination showed minimal IVC
      fibrosis and intimal hyperplasia. SEM showed endothelium on the IVC surface at
      the filter implantation site and a presumed endothelial layer covering partially
      or totally the struts. The interface filter-IVC was covered by deposits of
      leucocytes and platelets. No signs of pulmonary embolism were found in all
      pulmonary angiograms of both groups. CONCLUSION: The modified filter presented
      good biocompatibility, stability and absence of thrombogenicity at 12 months. It
      presented low tendency to tilting and extrusion of struts. The long-term
      histopathologic alterations in vena caval wall were minimal and the appearance of
      the studied filters in the IVC was similar to stents placed in the arterial
      system.

PMID- 15507897
TI  - Modifications of plasma concentrations of hormonal and tissue factors during
      mechanical ventilation with positive end-expiratory pressure.
AB  - AIM: The aim of this study is to analyse if the decrease of cardiac performance
      due to positive end-expiratory pressure (PEEP) application, within low values
      applied in clinical practice (5 cm H(2)O) is able to trigger a response of the
      main endogenous factors which control and maintain the mean arterial pressure
      (MAP). METHODS: This study was applied to 18 patients, admitted to the Intensive
      Care Unit (ICU) of the University Hospital of Modena, who underwent oro-tracheal
      intubation and mechanical ventilation. On admission, patients did not suffer from
      cardiac or lung disease. This study analyses plasma concentrations of
      epinephrine, norepinephrine, ET-1, NO metabolites, renin, aldosterone at 4
      different times: before PEEP application, 60 minutes after the beginning of
      mechanical ventilation with PEEP, and respectively 30 and 60 minutes after
      withdrawal of PEEP. At the same time, MAP values and heart rate (HR) have been
      observed. RESULTS: Results show an increase of epinephrine and norepinephrine
      after PEEP application and a decrease to basal values at PEEP withdrawal. All
      variations are statistically significant. After PEEP introduction, ET-1 showed an
      increased concentration, although it was not statistically significant, while a
      significant decreasing trend was observed after PEEP withdrawal. A significant
      increase of NO metabolite values has been observed together with the increase of
      ET-1, followed by a decrease to basal values after the withdrawal of PEEP.
      Concentrations of renin increased when PEEP was applied even though they were not
      significant and decreased significantly when PEEP was withdrawn. A similar trend
      was revealed by aldosterone even though it underwent constant significant
      variations. CONCLUSION: The administration of PEEP produces an effective response
      of endogenous substances whose function is to maintain a proper tissue perfusion.

PMID- 15507898
TI  - Screening men for aortic aneurysm.
AB  - AIM: Ruptured abdominal aortic aneurysm (rAAA) accounts for 10000 deaths annually
      in the UK. Deaths occur in the 6th and 7th decades with loss of potential years
      of life. Mortality rates of 5% to 8% are reported for elective AAA repair, but no
      significant improvement in emergency outcome, with community mortality remaining
      at 80% and operative mortality at 50%. Patients surviving have several years life
      expectancy, regardless of age, and good quality of life. The difference suggests
      that overall emergency mortality could be significantly reduced by earlier
      diagnosis with widespread screening of the at risk population. Previous studies
      suggest screening men over 65 years significantly reduces incidence of rupture
      and aneurysm related death. Patients with abdominal aortic aneurysm (AAA) have a
      high prevalence of coronary artery disease (CAD) and vice versa. There is
      mounting evidence that screening men for AAA reduces rAAA mortality, especially
      in high-risk groups. A limited screening study of CABG patients was introduced.
      METHODS: Patients on the waiting list for coronary artery bypass grafting (CABG)
      (n=118) had a single duplex scan of the abdominal aorta. Aortic diameter of >2.6
      cm was considered abnormal. RESULTS: Eighteen AAAs were detected (15.3%), 5
      required surgery, 13 underwent surveillance. Mean age at detection was 64.8 years
      with a range of ages between 60 and 72 years. CONCLUSION: Patients with
      symptomatic CAD have a high incidence of AAA, with significant risk of rupture in
      the perioperative period post-CABG. Screening should form part of the routine
      work-up for coronary revascularisation. Staged repair should be considered with
      AAA greater than 5.5 cm diameter.

PMID- 15507899
TI  - A renal artery aneurysm incidentally found at operation. Should it be resected?
AB  - A rare case of a patient with a ruptured abdominal aortic aneurysm (AAA) and an
      incidentally found left renal artery aneurysm (RAA) is presented. Successful
      repair of both aneurysms was simultaneously performed. The indications for such a
      surgical approach are also discussed.

PMID- 15507900
TI  - News from the editorial council.

PMID- 15507901
TI  - Complete denture prosthodontics--the state of the art. 1975.

PMID- 15507902
TI  - A multidisciplinary approach to restoring an acquired palatal defect using
      distraction osteogenesis: a clinical report.
AB  - Prosthetic and surgical procedures can be applied to rehabilitate acquired
      palatal defects. Distraction osteogenesis may be used to narrow the defect to
      facilitate bone and soft tissue closure. This clinical report describes a
      multidisciplinary approach to the closure of a palatal defect with distraction
      osteogenesis, comprehensive orthodontic treatment, surgical soft tissue flap
      reconstruction of the residual soft tissue defect, implant placement in the newly
      created edentulous ridge, and restoration with an implant-supported prosthesis.

PMID- 15507903
TI  - Prosthetic rehabilitation for a patient with microstomia: a clinical report.
AB  - This clinical report describes the fabrication of a collapsible maxillary
      removable complete overdenture using a sectional impression tray technique and a
      custom-made palatal hinge mechanism for a partially edentulous woman with
      microstomia resulting from scleroderma. As microstomia is frequently associated
      with poor manual dexterity, an instrument was fabricated to assist the patient in
      removing the prosthesis.

PMID- 15507904
TI  - Stress transfer of four mandibular implant overdenture cantilever designs.
AB  - STATEMENT OF PROBLEM: The influence of implant number and cantilever design on
      stress distribution on bone has not been sufficiently assessed for the mandibular
      overdenture. PURPOSE: The purpose of this simulation study was to measure,
      photoelastically, the biologic behavior of 2 or 3 implants retaining different
      designs of cantilevered bar mandibular overdentures and to compare load
      characteristics. MATERIALS AND METHODS: Two photoelastic models of a human
      edentulous mandible were fabricated having 2 or 3 screw-type implants (Nobel
      Biocare, 3.75 x 10mm) embedded in the parasymphyseal area. Bar frameworks using a
      7-mm cantilever were fabricated for both models. A clip-retained and a plunger
      retained (SwissLoc) prosthesis were fabricated as superstructures for each
      framework. Vertical loads of 15 and 30 pounds were applied unilaterally to the
      first molar and 15 pounds to the first premolar on each of the 4 standardized
      overdenture prostheses. The cantilever was removed from the 2-implant framework
      and the clip-retained prosthesis was loaded similarly on the first molar with 25
      pounds. Stresses that developed in the supporting structure were monitored
      photoelastically and recorded photographically. RESULTS: While all 4 prostheses
      demonstrated low stress transfer to the implants, the plunger-retained prosthesis
      caused more uniform stress distribution to the ipsilateral terminal abutment
      compared to the clip-retained prosthesis and provided retention security under
      tested loads. The plunger-retained prosthesis retained by 2 implants provided
      better load sharing from the ipsilateral edentulous ridge than the clip-retained
      prosthesis retained by 3 implants, and lower resultant stresses were seen on the
      implants. CONCLUSIONS: Under load, all prosthetic designs demonstrated a low
      stress transfer to the ipsilateral abutment and to the contralateral side of the
      arch. The plunger-retained prosthesis retained by 2 implants demonstrated a more
      uniform stress transfer to the ipsilateral terminal abutment than the clip
      retained prosthesis retained by 3 implants and provided more retention, given the
      implant configuration, prosthetic design and arch form.

PMID- 15507905
TI  - Effect of different peroxide bleaching regimens and subsequent fluoridation on
      the hardness of human enamel and dentin.
AB  - STATEMENT OF PROBLEM: Bleaching of teeth by "in-office" or "home" bleaching
      techniques are popular methods of whitening teeth. However, bleaching may reduce
      the surface hardness of enamel and dentin. PURPOSE: The purpose of this study was
      to evaluate (1) the effect of different concentrations of 2 "in-office bleaching"
      and 2 "home bleaching" agents applied for different time periods on the hardness
      of enamel and dentin and (2) the effect of subsequent immersion in a low
      concentration fluoride solution on the hardness of bleached enamel and dentin.
      MATERIAL AND METHODS: The enamel and dentin of 12 extracted intact human molar
      teeth were sectioned lengthwise, ground, polished, embedded in acrylic resin and
      divided into 4 groups each (n=12). An area of approximately 5 x 5 mm of enamel
      and dentin tested for Knoop hardness number (KHN; kg/mm 2 ) at a load of 100 g
      for 20 seconds (baseline). The specimens were stored in distilled water for 1
      hour and the microhardness testing repeated as a control group. The groups were
      bleached as follows: Group OX and Group OQ were bleached "in office" with
      Opalescence Xtra (35% hydrogen peroxide) and Opalescence Quick (35% carbamide
      peroxide), respectively, for 5, 15, or 35 minutes and retested for KHN at the end
      of each time period. "Home bleaching" products Opalescence F (15% carbamide
      peroxide) and Opalescence (10% carbamide peroxide) were applied in 14-hour
      applications at 24-hour intervals to Groups OF and O, respectively, which were
      then tested for KHN. Specimens were immersed in 0.05% fluoride solution (Meridol)
      for 5 minutes and retested for KHN. The hardness values were analyzed by 2-way
      ANOVA and Scheffe post hoc test (alpha=.05). Comparisons of KHN between each time
      and the baseline measurement for each group were of interest. RESULTS:
      Significant decreases in KHN of enamel and dentin were found after bleaching for
      all test groups, dependent on the accumulated bleaching time. Group OX showed a
      25% KHN reduction for enamel and 22% for dentin after 35 minutes bleaching (P <
      .0001). Group OQ showed a 13% KHN reduction (P < .0001) for enamel and 10% for
      dentin after 35 minutes (P < .005). Group OF showed a KHN reduction of 14% for
      enamel (P < .05) and 9% for dentin (P < .0001) after 14 hours bleaching, and
      Group O showed an 18% reduction in enamel (P < .0001) and 13% in dentin (P <
      .0001) for the same period. Fluoridation completely restored the softened dental
      tissues. CONCLUSION: The "in-office" bleaching technique reduced the hardness
      significantly more than the "home" bleaching technique. Low-concentration
      fluoride mouth rinse (Meridol) restored the softened dental tissues.

PMID- 15507906
TI  - Influence of acidulated phosphate fluoride solution on the color stability of
      indirect composites.
AB  - STATEMENT OF PROBLEM: Although acidulated phosphate fluoride (APF) agents are
      known to be useful for caries-preventive interventions, few studies have examined
      the influence of APF agents on indirect composite materials. PURPOSE: This study
      examined whether exposure to APF agents affects color stability when a composite
      is exposed to a common staining agent. MATERIALS AND METHODS: Forty light
      polymerized composite disks (8 x 2.0 mm) were fabricated with midifilled (Cesead
      II; n = 20) and microfilled (Newmetacolor Infis; n = 20) composites. The
      specimens were polymerized with a light for 90 seconds on each side, ground with
      silicon carbide paper, finished using a polishing kit, and colorimetrically
      evaluated to determine baseline L*a *b* values. After storage in distilled water
      at 37 degrees C for 24 hours, half of the disks for each composite (n = 10) was
      treated with an APF solution (Fluodent A) for 32 minutes, while the remaining
      half of the specimens were untreated (controls). Half the treated and untreated
      specimens were immersed in tea or distilled water (n = 5, respectively), and
      after 4 weeks color changes were measured. To determine the influence of APF on
      each composite, the CIE L*a*b* color difference baseline values after 4 weeks
      were compared using 2- and 1-way analyses of variance and post-hoc Sheffe's S
      intervals (alpha=.05). RESULTS: The color differences of both materials when
      immersed in tea were significantly influenced by APF (P < .05). The mean DeltaE
      values of APF-treated Cesead II and Newmetacolor Infis immersed in tea were 5.4
      +/- 1.2 and 4.5 +/- 1.3, respectively, while the untreated values were 3.8 +/-
      0.6 and 3.0 +/- 0.1, respectively. When immersed in water, neither material was
      affected by APF in respect to change in color. CONCLUSION: The color of both
      composites tested were significantly influenced by APF treatment when immersed in
      tea, indicating that the in vitro color stability of the indirect composites was
      negatively affected by applications of APF.

PMID- 15507907
TI  - Thermo-hydrolytic stability of core foundation and restorative composites.
AB  - STATEMENT OF PROBLEM: The use of weak and less durable materials in restoring
      teeth may result in weak restorations unable to withstand intraoral conditions.
      PURPOSE: The purposes of this study were to evaluate the effect of thermo
      hydrolytic stress on the flexural strength and flexural modulus of core
      foundation composites with direct restorative composites and determine mass
      percentage of filler content. MATERIAL AND METHODS: A total of 216 specimens,
      from 9 brands of commercially available composites (Coreflo, DC Core, Photocore,
      APX, Litefil II A, Surefil, TPH Spectrum, Z100, and Z250) were fabricated
      following ISO Standard 4049. Flexural strength (MPa) and flexural modulus (GPa)
      were determined on bar-shaped specimens (25 x 2 x 2 mm) before and after storage
      in boiling water for 24 hours (n=12). The filler content in composite was
      determined by incineration using a thermogravimetric analyzer. The data were
      analyzed using 2-way analysis of variance and the Student t test (alpha=.05).
      RESULTS: Filler content of the tested composites was 66.6 to 81.8 mass %.
      Significant differences in both flexural strength and flexural modulus existed
      among materials, the effect of boiling and interaction (P<.05). Coreflo, DC Core,
      Z100, and Z250 demonstrated a significant decrease in flexural strength after
      boiling (P<.05). Z250 showed a significant decrease in flexural modulus after
      boiling (P=.001), while Surefil showed a significant increase in flexural modulus
      (P=.007). CONCLUSION: Within the limitations of this study, it can be concluded
      that composites were affected differently by moist heat stress. Some composites
      showed a degradation of flexural properties while some retained flexural
      properties. Stability of the composites varied among brands.

PMID- 15507908
TI  - Distortion of disposable plastic stock trays when used with putty vinyl
      polysiloxane impression materials.
AB  - STATEMENT OF PROBLEM: Impressions are made using high-viscosity putty vinyl
      polysiloxane impression materials in conjunction with disposable plastic stock
      trays. The impression materials have been shown to be dimensionally stable.
      However, it remains unclear if the disposable plastic stock trays are rigid
      enough to resist deformation thus yielding potentially unreliable results.
      PURPOSE: This study evaluated the rigidity and ability to resist deformation of 6
      commercially available disposable plastic stock trays and 1 metal stock tray when
      used in conjunction with a high-viscosity vinyl polysiloxane impression material.
      MATERIAL AND METHODS: Ten impressions were made with 1 putty vinyl polysiloxane
      material (Reprosil Putty) using each of the 6 tested disposable plastic stock
      trays, Sani-Trays (perforated), Sani-Trays (nonperforated), COE Disposable Spacer
      Tray (perforated), COE Disposable Spacer Tray (nonperforated), Bosworth Tray
      Aways (perforated), Track-it Trays (perforated), and 1 metal stock tray
      (nonperforated), Cadco Dental Products, as a control on a mandibular plastic
      model. The dimensions of the tray in cross section at the mandibular right first
      molar area were measured before, during, and after the impression procedures with
      an electronic digital caliper. The cross-arch dimensions of the tray were
      measured at similar intervals. One examiner made all measurements and each
      measurement was repeatable within +/-0.01 mm. A split plot repeated measures
      analysis of variance (ANOVA) was performed and 2-sided P -values were calculated
      (alpha=.05). RESULTS: The results indicated that the disposable plastic trays
      tested were not sufficiently rigid to resist deformation when used with very high
      viscosity putty material. Metal stock trays showed significantly less change in
      cross-arch dimension than plastic trays (F(1.68)=11.25, P =.001). Metal stock
      trays also showed significantly less change in cross-sectional arch dimension
      than plastic trays (F(1.68)=15.15, P<.001). CONCLUSION: When disposable plastic
      stock trays were tested in conjunction with very high-viscosity impression
      materials there was distortion of the tray both across the arch and in cross
      section.

PMID- 15507909
TI  - Influence of different adhesive resin cements on the fracture strength of
      aluminum oxide ceramic posterior crowns.
AB  - STATEMENT OF PROBLEM: The influence of different types of adhesive resin cements
      on the long-term prognosis of aluminum oxide ceramic posterior crowns is unclear.
      PURPOSE: The purpose of this study was to evaluate the fracture resistance of
      aluminum oxide ceramic on maxillary posterior crowns cemented with different
      resin luting agents before and after cyclic thermomechanical loading. Material
      and methods Forty-eight maxillary first molars were prepared and restored with
      standardized aluminum oxide ceramic (In-Ceram Alumina) crowns. The test specimens
      were randomly divided into 3 groups (n=16). The crowns were luted with an acrylic
      resin cement (Super-Bond C&B, control, Group SB) and 2 composite luting agents
      (Panavia F, Group PV; and Rely X Unicem, Group RX). Half of the specimens were
      exposed to thermomechanical fatigue in a masticatory simulator. All specimens
      were tested for fracture strength (N) using quasistatic loading. The Wilcoxon
      rank sum test was used to compare the fracture strength (alpha=.05). RESULTS: All
      specimens survived the exposure to the simulator. The following median fracture
      strength values were obtained without/with thermomechanical fatigue loading:
      Group SB, 2726 N/2673 N; Group PV, 2520 N/2083 N; and Group RX, 2036 N/2369 N.
      The fracture strength in Group PV after thermomechanical fatigue loading was
      significantly lower compared to the fracture strength in Group PV without
      artificial aging (P =.016), as well as significantly lower compared to Group SB
      with artificial aging (P =.003). CONCLUSION: Within the limitations of this
      study, all tested cements are capable of successfully luting aluminum oxide
      ceramic crowns. The fracture strength of Group PV after artificial aging was
      comparatively low.

PMID- 15507910
TI  - In vitro fracture resistance of posterior metal-ceramic and all-ceramic inlay
      retained resin-bonded fixed partial dentures.
AB  - STATEMENT OF PROBLEM: Inlay-retained resin-bonded fixed partial dentures (RBFPDs)
      are conservative prosthetic restorations; however, their resistance to fracture
      is not clear. PURPOSE: The purpose of this study was to compare fracture loads of
      posterior complete coverage metal-ceramic restorations with all-ceramic inlay
      retained RBFPDs. MATERIAL AND METHODS: Thirty-two posterior ceramic RBFPD
      restorations were divided into 4 groups (n=8): (1) Complete metal-ceramic fixed
      partial dentures (MC-FPDs) fabricated of Ni-Cr-based alloy (Wirolloy) and
      veneered with a ceramic (IPS d.SIGN) as the control group; (2) inlay-retained
      metal-ceramic (MC RBFPDs) with the same materials as the control; (3) inlay
      retained lithium disilicate (LD) glass-ceramic (IPS Empress 2) RBFPDs; and (4)
      inlay-retained zirconia-based (Z) ceramic (Cercon) RBFPDs. Control specimens were
      prepared to receive conventional complete MC-FPDs designed to include a 1.3-mm
      circumferential, 90-degree flat shoulder with rounded angles. Inlay-retained
      RBFPD specimens were prepared with 2-mm occlusal reduction but without bevels at
      the occlusal or gingival margins. Specimens were loaded and fracture loads (N)
      measured at fracture with a universal testing machine at a crosshead speed of 1.0
      mm/min and 250 kgf load cell. Data were analyzed with 1-way ANOVA and Duncan test
      (alpha=.001). RESULTS: Fracture loads (mean +/- SD) were greatest for control
      specimens (1318.43 +/- 211.00 N) and Z-RBFPD (1247.70 +/- 262.51 N) specimens as
      compared to MC-RBFPD or LD-RBFPD (P < .001). MC-RBFPD exhibited the next highest
      fracture loads (958.01 +/- 194.29 N), and LD-RBFPD exhibited the significantly
      lowest values (303.23 +/- 92.54 N) of the materials tested (P < .001).
      CONCLUSION: Inlay-retained zirconia-based ceramic RBFPDs demonstrated the
      greatest fracture resistance among all inlay-retained restorations tested.

PMID- 15507911
TI  - Designing visually optimal shade guides.
AB  - STATEMENT OF PROBLEM: Dental shade guides do not provide a broad coverage of
      tooth colors. There is a need for shade guides that can provide closer color
      matches. PURPOSE: The purpose of this study was to propose and assess a visually
      optimal shade guide for tooth color matching. MATERIAL AND METHODS: With the use
      of a spectrophotometric approach, the color distribution (L*a*b*) of 150
      extracted human teeth and 3 commercially available shade guides (Vita Lumin V,
      Trubyte Bioform Color Order Shade Guide, and Vitapan 3D-Master Shade System) was
      measured. With the use of a hierarchical clustering approach, a series of shade
      guides was designed with a varying number of tabs. The average error (DeltaE)
      between colors from each shade guide and the extracted teeth was computed.
      RESULTS: The proposed visually optimal shade guide had the smallest average error
      of all guides tested. The new guide achieved lower error with fewer shade tabs
      than the 3 commercial systems evaluated. CONCLUSION: Within the limitations of
      this study, it was demonstrated that a hierarchical clustering technique can be
      used to design a visually optimal shade guide for a given population with a
      flexible degree of control over the mean error and number of tabs.

PMID- 15507912
TI  - Porosity of cpTi casting with four different casting machines.
AB  - STATEMENT OF PROBLEM: Porosity is a well-known problem in dental titanium
      casting, resulting in inferior mechanical properties of dental restorations.
      PURPOSE: The aim of this study was to evaluate the porosity of cpTi castings
      produced with different casting machines. MATERIAL AND METHODS: Four groups of 20
      rectangular (30 x 3 x 0.5 mm) wax patterns were fabricated. Group CyII was cast
      in a CyclarcII casting machine, Group DAM in a Dor-A-Matic, Group TiF in a Titec
      201F, and Group ETi in an EasyTi with cpTi, according to manufacturers'
      instructions. Groups CyII, DAM and TiF were invested with magnesia based Titavest
      CB and Group ETi with Ticoat S+L silica based investment. The percentage porosity
      of each specimen was determined using standardized digital radiographs and
      calculated by quantitative image analysis procedure. The results were
      statistically analyzed by nonparametric Kruskal-Wallis test (alpha=.05). RESULTS:
      No statistical differences were found among the groups tested; nevertheless, pore
      distribution among the specimens of the same group was inhomogeneous. The results
      show that the casting machines tested produced nonuniform porosity. CONCLUSIONS:
      Under the conditions of the present study, the type of casting machine does not
      significantly influence the internal porosity in cpTi castings.

PMID- 15507913
TI  - Effect of chemical disinfectants on the transverse strength of heat-polymerized
      acrylic resins submitted to mechanical and chemical polishing.
AB  - STATEMENT OF PROBLEM: Immersion in chemical solutions used for cleansing and
      disinfecting prostheses can decrease the strength of denture base resins, making
      them more prone to fracture during use. PURPOSE: The purpose of this study was to
      assess the effect of immersion in different chemical disinfectants for varying
      time periods on the transverse strength of 3 mechanically or chemically polished
      heat-polymerized acrylic resins. MATERIAL AND METHODS: A total of 630 rectangular
      specimens (65 x 10 x 3 mm), 210 per resin (Classico, Lucitone 550, and QC-20),
      were fabricated. One side of each specimen was not polished and the other was
      either mechanically (n=300) or chemically (n=300) polished, and immersed for 10,
      20, 30, 45, or 60 minutes in either 1%, 2.5%, or 5.25% sodium hypochlorite or 2%
      glutaraldehyde. Mechanically polished (n=15) and chemically polished (n=15)
      control specimens were immersed only in distilled water. The transverse strength
      (N/mm 2 ) was tested for failure in a universal testing machine, at a crosshead
      speed of 5 mm/min. Data were statistically analyzed using 2-way ANOVA and Student
      t test. Multiple comparisons were performed using Tukey and Scheffe tests
      (alpha=.05). RESULTS: There was significant difference (P < .01) between types of
      polishing, with chemical polishing resulting in lower transverse strength. ANOVA
      identified significant differences (P < .01) in strength between mechanically
      polished Lucitone 550 and QC-20, and among all 3 chemically polished resins. No
      significant differences were observed between resins submitted to both types of
      polishing or between different immersion periods (10 to 60 minutes),
      disinfectants, or interaction. CONCLUSIONS: Lucitone 550 resin presented the
      greatest transverse strength values with both types of polishing. Among the
      mechanically and chemically polished specimens, transverse strength was not
      affected after immersion in the disinfectants for the immersion periods tested
      (10 to 60 minutes). Chemically polished control and experimental (immersed in all
      solutions) QC-20 specimens showed significant differences in transverse strength
      values.

PMID- 15507914
TI  - A U-loop pressure clip for earlobe keloid.
AB  - Pressure therapy using custom-made pressure clips or splints is widely used for
      the treatment of ear keloid scars; however, it is often difficult to control the
      amount and direction of pressure applied. One of the most common complications of
      this therapy is ulceration due to excessive soft tissue pressure, resulting in
      delays and prolonged treatment time. This article presents a U-loop pressure clip
      of a novel design incorporating an adjustable U-loop component. This design
      allows for more control over the amount and direction of the pressure applied on
      the scar tissues.

PMID- 15507915
TI  - Fabrication of a custom diving mouthpiece using a thermoforming material.
AB  - Scuba divers may suffer from temporomandibular joint dysfunction and related
      problems associated with the use of commercially available diving mouthpieces.
      Several authors have recommended that custom diving mouthpieces be fabricated for
      relieving the symptoms of diver's mouth syndrome. The lost wax technique is
      commonly used for this purpose but may be time-consuming and is technically
      complicated. This article describes a simplified technique using thermoforming
      material for fabricating a custom diving mouthpiece.

PMID- 15507916
TI  - Clinical application of surgical fixation screws in implant prosthodontics--Part
      I: positioning of radiographic and surgical templates.
AB  - Proper implant position and angulation are fundamental for functional and optimal
      esthetic implant rehabilitation. This article describes the clinical application
      of surgical microfixation screws for stabilization and support of radiographic
      and surgical templates in edentulous patients. These screws provide fixed
      reference points for exact positioning of a diagnostic device.

PMID- 15507917
TI  - Prosthodontic application for implant carriers.
AB  - This article describes and illustrates clinical and laboratory prosthodontic
      procedures for the use of an implant carrier as surgical guide, positional index,
      impression coping, verification device, provisional abutment, implant-supported
      record base, and occlusal registration stop.

PMID- 15507918
TI  - Direct procedure for connecting a mandibular implant-retained overdenture with
      ball attachments.

PMID- 15507919
TI  - Conflict of interest.

PMID- 15507920
TI  - Maternal corticotropin-releasing hormone, fetal growth, and preterm birth.

PMID- 15507921
TI  - Preeclampsia: an inflammatory syndrome?

PMID- 15507922
TI  - Placental corticotropin-releasing hormone (CRH), spontaneous preterm birth, and
      fetal growth restriction: a prospective investigation.
AB  - OBJECTIVES: Recent advances in the physiology of human pregnancy have implicated
      placental corticotropin-releasing hormone (CRH) as one of the primary endocrine
      mediators of parturition and possibly also of fetal development. The aim of this
      study was (1) to prospectively assess the relationship of maternal plasma
      concentrations of CRH in the early third trimester of gestation with two
      prematurity-related outcomes-spontaneous preterm birth (PTB), and small-for
      gestational age birth (SGA), and (2) to determine whether the effects of CRH on
      each of these outcomes are independent from those of other established obstetric
      risk factors. STUDY DESIGN: In a sample of 232 women with a singleton,
      intrauterine pregnancy, maternal plasma was collected at 33 weeks' gestation and
      CRH concentrations were determined by radioimmunoassay. Each pregnancy was dated
      on the basis of last menstrual period and early ultrasonography. Parity,
      obstetric risk conditions for prematurity, mode of delivery, and birth outcomes
      were abstracted from the medical record. RESULTS: After adjusting for the effects
      of established obstetric risk factors, elevated CRH levels at 33 weeks' gestation
      were significantly associated with a 3.3-fold increase in the adjusted relative
      risk (RR) for spontaneous preterm birth and with a 3.6-fold increase in the
      adjusted relative risk for fetal growth restriction. Women who delivered postterm
      had significantly lower CRH levels in the early third trimester than those who
      delivered at term. When outcomes were stratified by gestational length and birth
      weight, the lowest CRH levels at 33 weeks' gestation were associated with the
      term non-SGA births, intermediate and approximately equal CRH levels were
      associated with the preterm non-SGA and term SGA births, and the highest CRH
      levels were associated with the preterm SGA births. CONCLUSION: For deliveries
      occurring after 33 weeks' gestation (the time of CRH sampling in this study), our
      findings support the notion that in humans placental CRH may play an impending,
      direct role in not only the physiology of parturition but also in processes
      related to fetal growth and maturation. Our results also support the notion that
      the timing of onset of parturition may be determined or influenced by events
      occurring earlier in gestation rather than those close to the time of actual
      onset of labor (ie, the notion of a "placental clock").

PMID- 15507923
TI  - Design, execution, interpretation, and reporting of economic evaluation studies
      in obstetrics.
AB  - OBJECTIVE: The purpose of this article was to propose guidelines for the design,
      execution, interpretation, and reporting of economic evaluation studies in
      obstetrics. Study design We performed a PubMed search of economic evaluation
      articles to identify those articles that deal with the quality of published
      economic evaluation studies, the development of guidelines, and the development
      of checklists/guidelines for the reporting of economic evaluation studies. All
      other articles were excluded from the review. RESULTS: We identified 160
      articles. We included 8 articles in our review that reported on the quality of
      published economic analyses, 12 articles that reported on guidelines, and 3
      articles that reported on checklists/guidelines that are used by journals. There
      were 2 articles that dealt with the quality of published economic evaluations in
      obstetrics and gynecology, both of which showed less than optimal quality. There
      were only 4 articles that provided some general guidelines for the reporting of
      economic evaluations in obstetrics and gynecology. We found no articles on any
      checklist/guidelines for the reporting of economic evaluation studies in
      obstetrics and gynecology. CONCLUSION: There is a need to improve the design,
      execution, interpretation, and reporting of economic evaluation studies in
      obstetrics.

PMID- 15507924
TI  - Bed rest and other determinants of bone loss during pregnancy.
AB  - OBJECTIVE: The purpose of this study was to evaluate patterns of bone loss during
      pregnancy and potential influences. STUDY DESIGN: This was a prospective study of
      181 women receiving prenatal care at Magee-Womens Hospital or its auxiliary
      clinics in Pittsburgh, Pennsylvania, between 1992 and 1995. Bone mineral density
      was measured at approximately 16 and 36 weeks' gestation. RESULTS: Trabecular,
      but not cortical, bone loss occurred during pregnancy. Mean ultra-distal bone
      mineral density loss was 1.9% (95% CI 1.2-2.5) during the 20-week period. Women
      prescribed bed rest had an adjusted mean loss of 4.6% compared with 1.5% for
      women not prescribed bed rest ( P = .001) and 6-fold higher odds ( P = .001) of
      bone loss > or =5% during the 20-week period. Nulliparity, calcium intake < 2 000
      mg/day, low weight gain, and maternal age < 21 or >30 years were more modestly
      associated with greater bone loss. CONCLUSION: Substantial trabecular bone loss
      may occur during pregnancy, particularly in women prescribed bed rest. Study of
      postpartum bone recovery in such women is needed.

PMID- 15507925
TI  - Outcome of extremely-low-birth-weight infants at highest risk: gestational age <
      or =24 weeks, birth weight < or =750 g, and 1-minute Apgar < or =3.
AB  - OBJECTIVE: The purpose of this study was to evaluate neurodevelopmental outcome
      in extremely-low-birth-weight (ELBW) infants, all of whom had 3 characteristics:
      gestational age (GA) < or =24 weeks, birth weight < or =750 g, and 1-minute Apgar
      score < or =3. STUDY DESIGN: Surviving infants were evaluated at 18 to 22 months'
      corrected age with a neurologic examination and the Bayley II Mental and
      Psychomotor Developmental Index (MDI and PDI). RESULTS: Between 1993 and 1999,
      1016 infants had GA < or =24 weeks, birth weight < or =750 g, and 1-minute Apgar
      score < or =3. Of 246 survivors, 30% had cerebral palsy (CP), 5% had hearing
      impairment, and 2% were blind. MDI was > or =85 in 33% and < 70 in 46% of
      infants, while PDI was > or =85 in 41% and < 70 in 36% infants. Predictors of MDI
      < 70 were grade III-IV ICH, cystic periventricular leukomalacia (PVL), male
      gender, black race, and Medicaid insurance. Two-parent household was associated
      with an MDI >70. Predictors of PDI < 70 were grade III-IV ICH, PVL, steroids for
      bronchopulmonary dysplasia (BPD), and Medicaid insurance. CP was associated with
      grade III-IV ICH and PVL. CONCLUSION: Perinatologists and neonatologists should
      be aware of the risk of morbidity and mortality in this high-risk ELBW group.

PMID- 15507926
TI  - The endometrial echo revisited: have we created a monster?
AB  - Transvaginal ultrasound has been explored as an inexpensive, noninvasive,
      convenient way to indirectly visualize the endometrial cavity. For more than a
      decade numerous studies have indicated that a thin, distinct, well-visualized
      echo (<4-5 mm) in postmenopausal women with bleeding is as effective as any
      diagnostic modality in excluding endometrial cancer (99% negative predictive
      value). Unfortunately, this is not the same as saying that a thick endometrial
      echo is pathologic. In fact, the positive predictive value of an echo greater
      than 5 mm is less than 10% for any disease and only 4% for serious disease
      (cancer or hyperplasia). No studies validating the clinical significance of a
      nonthin endometrial echo observed in an incidental imaging study have ever been
      performed. Because 5 mm has been a "cutoff" for excluding endometrial cancers in
      women with bleeding, many clinicians have assumed that any findings greater than
      5 mm need endometrial sampling to exclude disease. The number of postmenopausal
      women with quiescent fibroids, or polyps, or heterogeneous uterine echoes for
      technical reasons (previous scarring, axial uterus) is unknown but not
      insignificant. Furthermore, if transvaginal ultrasound is to be used, it must be
      performed appropriately, further recognizing that in a substantial number of
      patients it may not be possible to obtain technically adequate endometrial
      assessment. So, although transvaginal ultrasound can be a reliable method of
      excluding disease in many postmenopausal women with bleeding, the incidental
      finding of a non-thin endometrial echo has not been investigated and should not
      automatically trigger a need for formal tissue sampling.

PMID- 15507927
TI  - Argument-based medical ethics: a formal tool for critically appraising the
      normative medical ethics literature.
AB  - Although there are critical appraisal tools for other genres of the medical
      literature, there currently is no formal tool for physicians to use in their
      critical appraisal of the normative medical ethics literature. We present a
      formal assessment tool for the critical appraisal of the normative medical ethics
      literature that incorporates the intellectual standards of argument-based medical
      ethics and evidence-based medicine. We draw on the intellectual standards of
      argument-based ethics, ethical analysis and argument, and the literature on
      evidence-based medicine. The tool involves 4 questions about normative medical
      ethics papers: (1) Does the article address a focused ethics question? (2) Are
      the arguments that support the results of the article valid? (3) What are the
      results? (4) Will the results help me in clinical practice? Obstetrician
      gynecologists can use this tool to appraise the normative literature of ethics in
      obstetrics and gynecology formally.

PMID- 15507928
TI  - Managing the sexually transmitted disease pandemic: a time for reevaluation.
AB  - The serious implications of the sexually transmitted disease (STD) pandemic that
      currently challenges educators, medical practitioners and governments suggest
      that prevention strategies, which primarily focus on barrier protection and the
      management of infection, must be reevaluated and that initiatives focusing on
      primary prevention of behaviors predisposing individuals to STD risk must be
      adopted. Human immunodeficiency virus/acquired immunodeficiency syndrome, human
      papillomavirus, genital herpes, and Chlamydia are used to illustrate the
      pervasive presence of STDs and their serious consequences for individuals and
      national infrastructures. Long-term sequelae are discussed, including the
      emerging link between various sexually transmitted infections and cancer, and the
      psychosexual and psychosocial factors which impact infected individuals. Although
      risk reduction and treatment of existing infection is critical, the promotion of
      optimal life-long health can be achieved most effectively through delayed sexual
      debut, partner reduction, and the avoidance of risky sexual behaviors.

PMID- 15507929
TI  - Surgical risk reduction: prophylactic salpingo-oophorectomy and prophylactic
      mastectomy.
AB  - Investigators have used retrospective and prospective study designs to provide
      much needed data on the extent of risk reduction after prophylactic oophorectomy
      and mastectomy in women at increased risk for breast and ovarian cancer. In this
      publication we identify those women who may wish to consider prophylactic
      surgery, review data demonstrating the efficacy of prophylactic surgery, and
      discuss potential surgical complications. We also present data about the
      frequency of use and psychosocial impact of prophylactic surgery in this
      typically young group of women. Finally, we provide general treatment guidelines
      for the practicing clinician.

PMID- 15507930
TI  - Antimicrobial resistance associated with the treatment of bacterial vaginosis.
AB  - OBJECTIVE: This study was undertaken to evaluate antimicrobial susceptibility of
      vaginal anaerobic bacteria before and after treatment of bacterial vaginosis.
      STUDY DESIGN: A randomized clinical trial of 119 nonpregnant women with bacterial
      vaginosis receiving either intravaginal metronidazole for 5 days or clindamycin
      for 3 days was performed. Women had 1 baseline and 3 follow-up visits at which
      quantitative vaginal cultures were performed. Anaerobic isolates underwent
      antimicrobial susceptibility testing. RESULTS: Complete susceptibility data was
      available on 95 women (47 metronidazole and 48 clindamycin). Of 1059 anaerobic
      bacterial isolates, less than 1% demonstrated resistance to metronidazole. In
      contrast, 17% demonstrated baseline clindamycin resistance, and 53% demonstrated
      resistance to clindamycin after therapy. Women exposed to clindamycin (but not
      metronidazole) had high frequencies (80%) of clindamycin-resistant anaerobic
      bacteria that persisted for 90 days after treatment. CONCLUSION: Treatment of
      bacterial vaginosis with clindamycin is associated with marked evidence of
      antimicrobial resistance among vaginal anaerobic bacteria. This may increase the
      vaginal reservoir of macrolide-resistant bacteria.

PMID- 15507931
TI  - Culture-independent analysis of vaginal microflora: the unrecognized association
      of Atopobium vaginae with bacterial vaginosis.
AB  - Although the pathogenesis of bacterial vaginosis remains elusive, a few
      microorganisms, such as Gardnerella vaginalis, are considered markers on Gram
      stain or culture. Culture-independent analysis of vaginal microflora using 16S
      rDNA cloning and sequencing of total bacterial communities reveals the gram
      positive Atopobium vaginae as a predominant species in disturbed vaginal flora.

PMID- 15507932
TI  - Retained products of gestation in miscarriage: an evaluation of transvaginal
      ultrasound criteria for diagnosing an "empty uterus".
AB  - OBJECTIVE: The purpose of this study was to compare clinical outcomes of
      conservative management versus surgical evacuation of retained products of
      gestation after misoprostol treatment for first trimester spontaneous miscarriage
      using less restrictive transvaginal ultrasound criteria for diagnosing "empty
      uterus," which were managed conservatively. STUDY DESIGN: This was a prospective,
      randomized, controlled trial. RESULTS: Forty-six patients who had sonographic
      features previously regarded as significant retained products of gestation after
      misoprostol treatment, ie, homogenous intrauterine dimension of more than 11 cm 2
      in combined transverse and sagittal plane, or those with heterogeneous
      intrauterine contents were consented to randomization. The short-term
      complication rates of those managed conservatively were significantly higher than
      surgical evacuation ([9/24] 37.5% vs [0/21] 0%, P < .05). CONCLUSION: Our
      previously reported transvaginal ultrasound criteria of homogenous intrauterine
      dimension of less than 11 cm 2 in combined transverse and sagittal planes for
      defining "empty uterus," which requires no further treatment, cannot be "relaxed"
      without incurring additional complications.

PMID- 15507933
TI  - Ten-year experience with laparoscopy on a gynecologic oncology service: analysis
      of risk factors for complications and conversion to laparotomy.
AB  - OBJECTIVE: The purpose of this study was to analyze our initial 10-year
      experience with laparoscopy and to determine risk factors for complications and
      conversions to laparotomy for technical difficulty. STUDY DESIGN: We reviewed the
      charts of all laparoscopic procedures from January 1991 through December 2000 and
      divided the procedures into 4 levels on the basis of the degree of difficulty:
      level I, diagnostic; level II, procedures on the uterus and/or adnexa; level III,
      second look operations for malignancy; and level IV, lymphadenectomies/other
      complex procedures. Complications were graded from 1 (mild) to 5 (death).
      Standard univariate and multivariate analyses were performed. RESULTS: We
      identified 1451 evaluable procedures. The number of complications was as follows:
      grades 1 to 5, 129 complications (9%); grades 3 to 5, 36 complications (2.5%). On
      multivariate analysis, older age ( P = .03), previous radiation ( P = .03), and
      malignancy ( P = .006) were associated with an increased risk of complications
      grades 3 to 5. Complication rates for grades 3 to 5 for patients with malignancy
      versus benign disease was 4% versus 1%, respectively. Technical difficulty led to
      conversion to laparotomy in 105 cases (7%). Previous abdominal surgery ( P <
      .001) significantly increased the rate of conversion to laparotomy; more complex,
      higher procedure levels were associated with a significant decrease in
      conversions ( P = .005). CONCLUSION: Both simple and complex laparoscopic
      procedures can be performed by a gynecologic oncology service with a low rate of
      complications and conversions to laparotomy. Older age, malignancy, previous
      radiation therapy, and previous abdominal surgery were identified as significant
      risk factors for complications and/or conversion and should be taken into account
      in patient selection, preoperative counseling, and surgical planning.

PMID- 15507934
TI  - Dose of progestin in postmenopausal-combined hormone therapy and risk of
      endometrial cancer.
AB  - OBJECTIVE: We studied the impact of progestin dose on this risk. The pattern and
      number of days per month that progestin is given in postmenopausal combined
      hormone therapy appears to affect endometrial cancer risk. We assessed the impact
      of progestin dose on this risk. STUDY DESIGN: A population-based, case-control
      study included 647 cases with endometrial cancer and 1209 controls. RESULTS:
      Among users of estrogen with medroxyprogesterone acetate (MPA) 10 to 24
      days/month, women who took >100 mg/month had an endometrial cancer risk that was
      equal to that of hormone nonusers (95% CI 0.6-1.7). The corresponding relative
      risk was 0.8 (95% CI 0.5-1.5) in those who used a lower monthly MPA dose for 10
      to 24 days/month. Among users of a continuous combined hormone regimen, the risk
      of endometrial cancer was low relative to hormone nonusers, regardless of MPA
      dose. CONCLUSION: Among the combined hormone regimens most commonly used by
      postmenopausal women today, MPA monthly dose bears little or no relation to
      endometrial cancer risk.

PMID- 15507935
TI  - Who will benefit from pelvic floor muscle training for stress urinary
      incontinence?
AB  - OBJECTIVE: The purpose of this study was to determine which patient
      characteristics are predictive of outcome before pelvic floor muscle training for
      stress urinary incontinence. STUDY DESIGN: This was an observational study at a
      single-center outdoor patient clinic in Brussels, Belgium, that comprised 447
      women, aged 26 to 80 years (mean, 52.7 years), who had urinary stress
      incontinence. All the women received individual pelvic floor muscle training
      under the guidance of the same physiotherapist. Twenty-two patient
      characteristics were considered for outcome measurements. RESULTS: Forty-nine
      percent of the women considered their treatment to be successful; 51% of the
      women had experienced only some improvement, no change, or a worsening of their
      condition or had interrupted therapy. Three independent predictors of treatment
      failure were > or =2 leakages per day before treatment ( P < .0001), the chronic
      use of psychotropic medication ( P = .002), and a baseline positive stress test
      result at first cough ( P = .042). The odds were only 15% for an individual
      patient to be treated successfully when these 3 predictors were present.
      CONCLUSION: Pelvic floor muscle training is beneficial in one half of the
      patients who are treated in this manner. Two or more leakages per day at baseline
      and the chronic use of psychotropic medication significantly predicted therapy
      failure.

PMID- 15507936
TI  - Tolerability of levonorgestrel emergency contraception in adolescents.
AB  - OBJECTIVE: We evaluated the tolerability of emergency contraception in
      adolescents. Study design In this descriptive study, 1 0.75 mg levonorgestrel
      tablet was administered to 52 females aged 13-16 with instructions to take the
      second tablet 12 hours later (unprotected intercourse was not an entry
      requirement). Participants kept diaries of side effects and menstrual patterns.
      We assessed correct use, side effects caused by treatment, and impact on
      menstrual cycle. RESULTS: Virtually all participants used the drug correctly,
      with no serious adverse events. Minor expected side effects occurred, including
      nausea, fatigue, and vomiting. There was no difference in reporting of side
      effects by age. Adolescents' mean duration of menses was comparable pre- and post
      treatment (5.3 vs 5.0 days; P=.146), and onset of menses was within the expected
      range. Ninety percent of participants reported they would recommend emergency
      contraception to a friend or relative if needed. CONCLUSION: Adolescents
      tolerated the medication well, experiencing transient side effects.

PMID- 15507937
TI  - Internalization of cytotoxic analog AN-152 of luteinizing hormone-releasing
      hormone induces apoptosis in human endometrial and ovarian cancer cell lines
      independent of multidrug resistance-1 (MDR-1) system.
AB  - OBJECTIVE: Eighty percent of human ovarian and endometrial cancers express
      receptors for luteinizing hormone-releasing hormone (LHRH-R). These receptors can
      be used for targeted chemotherapy with agents such as AN-152, in which
      doxorubicin is linked to analog [D-Lys(6)]-LHRH. Direct receptor-mediated
      antiproliferative effects of AN-152 have been shown in vitro and in vivo. In LHRH
      R positive cell lines, AN-152 was more effective than doxorubicin at equimolar
      concentrations. This study was designed to investigate the mechanism of action of
      AN-512 in ovarian and endometrial cancer cells in vitro. Study design Three
      ovarian (SKOV-3, NIH:OVCAR-3, EFO-21) and 2 endometrial carcinoma cell lines
      (Ishikawa, HEC-1A) were evaluated for doxorubicin- or AN-152-induced apoptosis.
      Internalization and cytoplasmic release of AN-152 was monitored by confocal laser
      scanning microscopy and inhibited by chloroquine. Cleavage of doxorubicin from AN
      152 was inhibited by carboxylesterase inhibitor, diisopropyl fluorophosphate
      (DFP). The surface expression of multidrug resistance-1 (MDR-1) gene product P
      glycoprotein (Pgp) was measured by flow cytometry. RESULTS: Induction of
      apoptosis by AN-152 in LHRH-R positive Ishikawa, HEC-1A, EFO-21, and NIH:OVCAR-3
      cells was significantly higher than that induced by doxorubicin, whereas the
      percentage of apoptotic cells in LHRH-R negative SKOV-3 was higher after
      treatment with doxorubicin. In EFO-21 cells, apoptosis induced by AN-152 was
      inhibited by pretreatment with chloroquine. Pretreatment with DFP increased AN
      152-induced apoptosis in LHRH-R positive cells and reduced apoptosis in LHRH-R
      negative SKOV-3. Both AN-152 and doxorubicin induced surface expression of MDR-1
      gene product Pgp, but the effect of AN-152 was smaller than that of doxorubicin.
      Pgp surface expression induced by AN-152 was inhibited by pretreatment with DFP.
      CONCLUSION: AN-152 is internalized through the LHRH-R and induces apoptosis in
      LHRH-R-positive human ovarian and endometrial cancer cell lines without
      activating the MDR-1 efflux pump system. The efficacy and specificity of AN-152
      is inversely correlated with carboxylesterase activity.

PMID- 15507938
TI  - Putative gene loci associated with carcinogenesis and metastasis of endocervical
      adenocarcinomas of uterus determined by conventional and array-based CGH.
AB  - OBJECTIVES: This study aimed to estimate the gene loci associated with
      carcinogenesis of endocervical adenocarcinoma of uterus (EA) and metastasis.
      Study design Sixteen patients with EA were studied; 6 had nodal metastasis. DNA
      was extracted from EAs, and subjected to both conventional comparative genomic
      hybridization (CGH) and array-based CGH. Copy number abnormalities were compared
      between cases with and without nodal metastasis. RESULTS: In all EAs, high
      frequencies of copy number losses were detected in genes LRP1B (on 2q21.2), DAB2
      (5p13), and DCC (18q21.3), as well as regions 3p, 16q, and 22q, and copy number
      amplifications in genes NRAS (1p13.2), TOP2A (17q21-q22), NCOA3(AIB1) (20q12),
      and ARSA (22q tel). Nodal metastasis was associated with high frequencies of copy
      number loss in genes PGRMC2 and LAMA3 and amplification in CDK6 and NCOA3(AIB1).
      CONCLUSION: This is the first report of gene copy number alterations spanning the
      whole genome in EA. These altered genes are speculated to be associated with EAs
      as a tumor suppressor and/or oncogene.

PMID- 15507939
TI  - A clinical trial demonstrates the analgesic activity of intravenous parecoxib
      sodium compared with ketorolac or morphine after gynecologic surgery with
      laparotomy.
AB  - OBJECTIVE: The purpose of this study was to compare the analgesic activity of 2
      doses of parecoxib sodium, ketorolac, and morphine with placebo after gynecologic
      surgery that requires laparotomy. STUDY DESIGN: In a randomized, controlled,
      double-blind, parallel-group study, 208 patients, after surgical hysterectomy,
      received single-dose intravenous placebo, parecoxib sodium 20 mg or 40 mg,
      ketorolac 30 mg, or morphine 4 mg followed by multiple-dose parecoxib sodium or
      ketorolac as needed. Primary efficacy variables were time to onset of analgesia,
      pain intensity differences, pain relief, time to first rescue/remedication, and
      global evaluation of study medication. RESULTS: Single-dose parecoxib sodium 40
      mg provided significantly better pain responses to placebo or morphine 4 mg and
      was comparable to ketorolac 30 mg. Multiple-dose parecoxib sodium 20 mg, 4 times
      daily, or 40 mg, twice daily, was comparable to ketorolac 30 mg, 4 times daily.
      Parecoxib sodium was well tolerated. CONCLUSION: Parecoxib sodium is an effective
      analgesic in the management of acute postoperative pain after laparotomy surgery.

PMID- 15507940
TI  - Altered monocyte function in experimental preeclampsia in the rat.
AB  - OBJECTIVES: In the present study, we evaluated functional activity of monocytes
      in experimental preeclampsia induced by low-dose endotoxin infusion. STUDY
      DESIGN: Pregnant (n = 12) and cyclic rats (n = 12) were equipped with a permanent
      jugular vein cannula and infused with either low-dose endotoxin or saline. One
      day before the infusion, and 4, 24, 72, and 168 hours after the infusion, blood
      samples (400 microL) were taken and white blood cell (WBC) and differential cell
      counts were measured. Samples were (re)stimulated with endotoxin, and the
      percentage of tumor necrosis factor-alpha (TNFalpha) producing monocytes was
      measured. RESULTS: During experimental preeclampsia, monocyte TNFalpha production
      is persistently decreased, while total WBC and granulocyte counts are
      persistently increased compared with normal pregnant rats. No persistent effect
      of endotoxin was found in cyclic rats. CONCLUSION: Because decreased endotoxin
      induced TNFalpha production is a feature of activated monocytes, the present
      results indicate that monocytes are persistently activated in experimental
      preeclampsia. Increased WBC counts and granulocyte numbers in these rats also
      point to an activated inflammatory response.

PMID- 15507941
TI  - Incidence, severity, and determinants of perineal pain after vaginal delivery: a
      prospective cohort study.
AB  - OBJECTIVES: The purpose of this study was to determine the frequency of perineal
      pain in the 6 weeks after vaginal delivery and to assess the association between
      perineal trauma and perineal pain. Study design This was a prospective cohort
      study of parturients at 1 day, 7 days,' and 6 weeks' post partum in an academic
      tertiary obstetric unit in Toronto, Canada. Four hundred forty-four women were
      followed up, including women with an intact perineum (n=84), first-/second-degree
      tears (n=220), episiotomies (n=97), or third-/fourth-degree tears (n=46). Primary
      outcome was the incidence of perineal pain on day of interview; secondary
      outcomes were pain score measurements and interference with daily activities.
      RESULTS: Perineal trauma was more common among primiparous women, those with
      operative vaginal deliveries, and those with epidural analgesia during the second
      stage of labor. The incidence of perineal pain among the groups during the first
      week was intact perineum 75% (day 1) and 38% (day 7); first-/second-degree tears
      95% and 60%; episiotomies 97% and 71%; and third-/fourth-degree tears 100% and
      91%. By 6 weeks, the frequency of perineal pain was not statistically different
      between trauma groups. CONCLUSION: Acute postpartum perineal pain is common among
      all women. However, perineal pain was more frequent and severe for women with
      increased perineal trauma.

PMID- 15507942
TI  - Development of a guinea pig model of chorioamnionitis and fetal brain injury.
AB  - OBJECTIVE: The purpose of this study was to develop a guinea pig model of
      chorioamnionitis to study the mechanisms that lead to fetal brain injury. Study
      design Pregnant guinea pigs at 70% gestation were inoculated intracervically with
      1000 to 2500 colony-forming units of Escherichia coli. Guinea pigs were killed 2
      to 3 days after bacterial inoculation. Maternal blood and fetal amniotic fluid
      samples were analyzed for proinflammatory cytokine tumor necrosis factor-alpha,
      interleukin-1beta, and interleukin-6 levels with the use of enzyme-linked
      immunosorbent assay kits. Fetal brains were stained for evidence of cell death
      with NeuroTacs stain. RESULTS: Of 34 maternal guinea pigs that were given an
      intracervical inoculation of E coli, 8 guinea pigs showed microbiologic evidence
      of chorioamnionitis in the amniotic fluid. Tumor necrosis factor-alpha and
      interleukin-6 were significantly higher (P<.05) in amniotic fluid samples that
      were obtained from sows that were subjected to intracervical inoculation with
      bacteria as compared with control animals (n=6 control maternal animals). These
      results were observed even if no bacteria were found subsequently on culture of
      the amniotic fluid from inoculated animals, which indicated that indirect
      exposure to infectious agents was sufficient to cause an elevated inflammatory
      response in the fetus. Levels of white matter injury were greater in fetuses that
      were exposed to bacterial infection in utero, as compared with control animals
      (P<.05). This result was found in the staining of periventricular and cortical
      white matter for the immunolabeling of activated caspase 3 and NeuroTacs staining
      for cells that exhibited evidence of apoptotic cell death (positive stain with
      evidence of karyorrhexis). CONCLUSION: Intracervical inoculation with E coli
      results in chorioamnionitis in guinea pigs that is associated with fetal brain
      injury.

PMID- 15507943
TI  - Meperidine for dystocia during the first stage of labor: A randomized controlled
      trial.
AB  - OBJECTIVE: This study was undertaken to evaluate whether the administration of
      meperidine decreases the length of labor in patients with a diagnosis of dystocia
      during the first stage of labor. STUDY DESIGN: Women with term singleton
      pregnancies who received a diagnosis of dystocia and required an active
      management of labor were randomly assigned to receive either 100 mg of meperidine
      or placebo. The primary outcome measure was length of labor. RESULTS: Four
      hundred seven pregnant women were included. There were no significant statistical
      differences between meperidine and placebo groups in length of labor and
      operative delivery rates such as forceps and cesarean section by intention-to
      treat analysis. Low Apgar scores, umbilical artery acidosis, and admission to
      neonatal care units were increased in the meperidine group. CONCLUSION: Because
      of the absence of any benefits in patients with dystocia in labor and the
      presence of harmful effects on neonatal outcomes, meperidine should not be used
      during labor for this specific indication.

PMID- 15507944
TI  - Anesthesia facilitation of external cephalic version: a meta-analysis.
AB  - OBJECTIVES: This study was undertaken to systematically review the medical
      literature to determine whether anesthesia facilitates the external cephalic
      version maneuver (ECV) for breech presentations. Study design A meta-analytic
      review of medical databases for randomized clinical trials comparing anesthesia
      with no anesthesia given for ECV attempts. The primary outcome was the immediate
      success of the ECV attempt. RESULTS: The literature search revealed only 4
      articles that met inclusion criteria. Four hundred eighty women participated in
      the studies and the use of anesthesia increased the success of ECV attempts
      (119/238 with anesthesia; 82/242 without anesthesia). The relative risk for this
      beneficial effect was 1.5 (95% CI 1.12-1.98) and number needed to treat was 7
      (95% CI 4-14). CONCLUSION: Further study is required to assess maternal and
      neonatal safety with anesthesia administered for ECV maneuvers.

PMID- 15507945
TI  - Previous pregnancy loss: risks related to severity of preterm delivery.
AB  - OBJECTIVES: The purpose of this study was to examine the association between
      previous pregnancy losses and subsequent risk of preterm delivery. STUDY DESIGN:
      A population-based Swedish study including information on all births and women's
      hospital admissions for pregnancy loss (n = 601,883) in Sweden between 1987 and
      2000 was performed. The risk of preterm delivery after a previous pregnancy loss
      was estimated using logistic regression models. The risk of preterm premature
      ruptures of the membranes (PROM), preterm labor, and other reasons for preterm
      delivery was also assessed. RESULTS: Previous spontaneous abortions and missed
      abortions were associated with increased risks of preterm delivery, and the risks
      increased with severity of preterm delivery. Previous pregnancy loss increased
      the risk of preterm PROM and preterm labor foremost in deliveries before 32
      weeks, but was not associated with other reasons of very preterm delivery.
      CONCLUSION: Our results support the hypothesis that pregnancy loss and early
      preterm delivery may share etiologic causes.

PMID- 15507946
TI  - Matrix metalloproteinases and their inhibitors in the cervical mucus plug at term
      of pregnancy.
AB  - OBJECTIVE: This study was undertaken to evaluate the presence of matrix
      metalloproteinases (MMPs) and their inhibitors in the cervical mucus plug
      obtained during active labor at term. STUDY DESIGN: Cervical mucus plugs from 17
      healthy women in normal active labor were homogenized, extracted, and analyzed by
      4 different assays. RESULTS: Gelatin zymography revealed large amounts of MMP-2
      and MMP-9, and triple-helical collagen degradation demonstrated collagenase
      activity (MMP-8). Reverse zymography showed that tissue inhibitor of matrix
      metalloproteinase 1 (TIMP-1) and TIMP-2 are detectable in the cervical mucus
      plug. Quantification by enzyme-linked immunosorbent assay confirmed the presence
      of MMP-2, MMP-8, MMP-9, and TIMP-1. CONCLUSION: Our results suggest that
      proteolytic or nonproteolytic effects of MMP and TIMP may play a part in the
      function of the cervical mucus plug of pregnancy.

PMID- 15507947
TI  - Soluble vascular endothelial growth factor receptor-1 (sFlt-1) is increased
      throughout gestation in patients who have preeclampsia develop.
AB  - OBJECTIVE: This study was undertaken to analyze prospectively circulating
      vascular endothelial growth factor (VEGF) and its soluble receptor, (s) Flt-1,
      throughout normotensive and preeclamptic pregnancies and to assess the importance
      of these proteins in the development of preeclampsia. STUDY DESIGN: In this
      longitudinal cohort study, serum samples were collected from recruited subjects
      throughout pregnancy at 12, 20, 30, and 37 weeks and in the 24 hours before and
      after delivery. Subjects were divided retrospectively into normotensive and
      preeclamptic groups. Circulating VEGF and sFlt-1 concentrations were analyzed by
      radioimmunoassay and enzyme-linked immunosorbent assay, respectively. RESULTS:
      Circulating sFlt-1 and VEGF significantly increased as gestation progressed and
      both were further elevated in preeclampsia compared with normotensive pregnancy.
      Soluble Flt-1 concentrations were elevated early in gestation and were
      significantly increased at 30 weeks' gestation in those who subsequently
      developed preeclampsia. CONCLUSION: These results indicate a definite association
      between elevated sFlt-1 concentrations and the onset of preeclampsia suggesting
      that sFlt-1 is linked with disease pathogenesis.

PMID- 15507948
TI  - Qualified and trained sonographers in the US can perform early fetal anatomy
      scans between 11 and 14 weeks.
AB  - OBJECTIVES: The objective of this study was to determine the extent to which
      normal fetal anatomy can be detected between 11- and 14-week scan by sonographers
      in the US. STUDY DESIGN: In a prospective cross-sectional study, 223 unselected
      women underwent a detailed assessment of fetal anatomy at 11 to 13 and 6/7 weeks
      by sonographers with transabdominal and/or transvaginal transducers. Thirty-seven
      structures were examined. Two groups were identified: group I: 121 patients
      between 11 and 12 weeks, and group II: 102 patients between 13 and 14 weeks.
      RESULTS: Structures other than the posterior fossa, heart, genitalia, and the
      sacral spine were seen between 64% to 99% for group I, and 72% to 98% for group
      II. The following structures were detected with statistically significantly
      higher rates in group II compared with group I: cerebellum, posterior fossa,
      face, 4-chamber view left ventricular outflow tract, aortic arch, ductal arch,
      kidneys, and genitalia. Comparing the patients of group I and group II, the
      transvaginal scans yielded a higher detection rate of structures than do the
      transabdominal scans. CONCLUSION: Anatomic surveys between 11 and 14 weeks can be
      performed by sonographers with good detection rates of most structures. Using the
      vaginal probe compared with the abdominal probe improved the detection rate at 13
      to 14 weeks as well as 11 to 12 weeks. If early fetal structure evaluation is to
      become customary in the US, the present practice of experienced and trained
      sonographers to scan such patients can be maintained.

PMID- 15507949
TI  - Frequency of uterine contractions in asymptomatic pregnant women with or without
      a short cervix on transvaginal ultrasound scan.
AB  - OBJECTIVE: The purpose of this study was to compare the frequency of uterine
      contractions in asymptomatic pregnant women with and without a short cervix (< 25
      mm) on transvaginal ultrasound (TVU) and to determine the additive risk of
      contractions on the risk of preterm birth. STUDY DESIGN: The study involved
      secondary analysis of a blinded observational study of asymptomatic singleton
      pregnancies who were at high risk for preterm birth and who received both home
      uterine activity monitoring daily and transvaginal ultrasound of the cervix at 22
      to 24 and 27 to 28 weeks of gestation. Thresholds for the maximum frequency of
      uterine contractions of 4 per hour and transvaginal ultrasound cervical length of
      25 mm were used for analysis. Contraction frequency was compared in women with
      cervical length < 25 mm and > or =25 mm and was correlated with the risk of
      spontaneous preterm birth at < 35 weeks of gestation. RESULTS: Of the 303 women
      whose pregnancy was evaluated at 22 to 24 weeks of gestation, the 39 women (13%)
      with a cervical length of < 25 mm had 1.6 +/- 2.7 versus 1.2 +/- 2.0 contractions
      per hour in the 264 women (87%) with a cervical length of > or =25 mm (P=.37). At
      27 to 28 weeks of gestation (n=295 women), contraction frequency was 3.2 +/- 3.7
      versus 2.8 +/- 3.1 contractions per hour in women with a cervical length of < 25
      mm (n=59 women; 20%) versus those with a cervical length of > or =25 mm (n=236
      women; 80%; P=.34). Among women with a short cervix, the relative risks for
      spontaneous preterm birth were 2.0 (95% CI, 0.95-4.2) and 2.1 (95% CI, 1.06-4.3)
      for women with > or =4 contractions per hour compared with women with < 4
      contractions per hour at 22 to 24 and 27 to 28 weeks of gestation, respectively.
      Results were confirmed by logistic regression analysis. CONCLUSION: The frequency
      of uterine contractions in asymptomatic women was not related significantly to
      cervical length of < 25 mm versus > or =25 mm. Among women with a cervical length
      of < 25 mm at 22 to 24 or 27 to 28 weeks of gestation, there was a trend toward a
      2-fold increased risk of spontaneous preterm birth when the maximum contraction
      frequency was > or =4 per hour, compared to < 4 per hour.

PMID- 15507950
TI  - Intrapartum fetal heart rate monitoring in cases of cytomegalovirus infection.
AB  - OBJECTIVE: Several studies have shown that abnormal intrapartum fetal heart rate
      patterns are the results from pre-existing fetal brain damage. We evaluated
      intrapartum fetal heart rate pattern of cytomegalovirus-infected fetuses and
      correlated the patterns with neurologic outcomes. STUDY DESIGN: Between 1991 and
      2001, there were 20 cytomegalovirus-infected fetuses. We selected 40 fetuses as
      control subjects that were matched for gestational age and birth weight. Fetal
      heart rate was interpreted according to the guidelines of the National Institute
      for Child and Human Development. The incidence of abnormal fetal heart rate
      pattern and umbilical blood gases were compared between both groups. We also
      investigated the factors that contributed to abnormal fetal heart rate pattern in
      the cytomegalovirus group. RESULTS: Nonreassuring fetal heart rate patterns
      (prolonged deceleration and recurrent late deceleration) were observed in 8 of 20
      fetuses (prolonged deceleration, 7 fetuses; recurrent late deceleration, 1 fetus)
      in the cytomegalovirus group and in 3 of 41 fetuses (prolonged deceleration, 1
      fetus; recurrent late deceleration, 2 fetuses) in the control group (P<.05,
      Fisher test). Baseline fetal heart rate variability was minimal in 4 of the 7
      prolonged deceleration cases in the cytomegalovirus group. Umbilical pH <7.1 was
      found for 1 fetus in the cytomegalovirus group. The average umbilical arterial pH
      values were similar in both the groups. In the cytomegalovirus group, there were
      no differences in the incidence of contributing factors between 8 fetuses with
      abnormal fetal heart rate pattern (prolonged deceleration and recurrent late
      deceleration) and 8 fetuses with no change. There were 3 fetuses with cerebral
      palsy: 2 fetuses in the no change group and 1 fetus in the prolonged deceleration
      group. Antigenemia was positive exclusively in 4 cases with abnormal fetal heart
      rate pattern (P<.05). CONCLUSION: Cytomegalovirus-infected fetuses are more
      likely to show abnormal intrapartum fetal heart rate patterns than low-risk
      control fetuses, which suggests that the perinatal detection of cytomegalovirus
      is necessary to distinguish hypoxic-ischemic encephalopathy.

PMID- 15507951
TI  - Comparison of maternal mortality and morbidity between trial of labor and
      elective cesarean section among women with previous cesarean delivery.
AB  - OBJECTIVE: This study was undertaken to assess the safety of trial of labor after
      previous cesarean delivery. STUDY DESIGN: Retrospective cohort study of 308,755
      Canadian women with previous cesarean delivery between 1988 and 2000. Occurrences
      of in-hospital maternal death, uterine rupture, and other severe maternal
      morbidity were compared between women with a trial of labor and those with an
      elective cesarean section. RESULTS: Rates of uterine rupture (0.65%), transfusion
      (0.19%), and hysterectomy (0.10%) were significantly higher in the trial-of-labor
      group. Maternal in-hospital death rate, however, was lower in the trial-of-labor
      group (1.6 per 100,000) than in the elective cesarean section group (5.6 per
      100,000). The association between trial of labor and uterine rupture was stronger
      in low volume (<500) than in high volume (> or =500 births per year) obstetric
      units. CONCLUSION: Trial of labor is associated with increased risk of uterine
      rupture, but elective cesarean section may increase the risk of maternal death.

PMID- 15507952
TI  - Fetal phenotypes and neonatal and early childhood outcomes in twins.
AB  - OBJECTIVES: The purpose of this study was to evaluate factors associated with,
      and postnatal consequences of, altered patterns of fetal growth in twins. STUDY
      DESIGN: Fetal growth was measured at 28 weeks' gestation on 218 twins, including
      head circumference, abdominal circumference, and femur length, and characterized
      as > or < or =10th %ile; children were followed up until the age of three years.
      Logistic regression was used to generate odds ratios of perinatal factors
      associated with reduced fetal growth. RESULTS: Maternal height <62 inches was
      associated with reductions in femur length (adjusted odds ratio [AOR] 3.88, 95%
      CI 1.42-10.57) and abdominal circumference (AOR 8.63, 95% CI 2.41-30.94), while
      primiparity had a protective effect on both of these fetal measurements (AOR
      0.28, 95% CI 0.13-0.64, and AOR 0.18, 95% CI 0.06-0.60, respectively), as well as
      head circumference (AOR 0.32, 95% CI 0.15-0.69). Smoking adversely affected femur
      and head growth (AOR 24.10, 95% CI 3.69-157.57, and AOR 10.82, 95% CI 1.73-67.79,
      respectively). Fetal reduction adversely affected femur and abdomen growth (AOR
      5.85, 95% CI 1.52-22.51 and AOR 4.90, 95% CI 1.01-23.86, respectively), and
      monochorionicity and maternal weight gain <0.65 lb/wk before 20 weeks adversely
      affected femur growth (AOR 5.47, 95% CI 1.65-18.10, and AOR 3.39, 95% CI 1.34
      8.59, respectively). At age 3 years, all categories of twins with reduced growth
      by 28 weeks' gestation were significantly shorter in height, and those with
      reduced abdominal circumference or head circumference at 28 weeks were also
      significantly lighter in weight compared with twins with adequate fetal growth by
      28 weeks' gestation. CONCLUSION: These data identify short maternal height,
      smoking, monochorionicity, fetal reduction, and inadequate weight gain before 20
      weeks as risk factors associated with reduced twin fetal growth by 28 weeks'
      gestation and significant residual reductions in height and weight through 3
      years of age.

PMID- 15507953
TI  - The occurrence of adverse events in women receiving continuous subcutaneous
      terbutaline therapy.
AB  - OBJECTIVE: The purpose of this study was to determine the frequency of serious
      adverse events in patients receiving continuous subcutaneous terbutaline after
      arrested preterm labor. STUDY DESIGN: Women with singleton, twin, and triplet
      pregnancies prescribed continuous subcutaneous terbutaline were studied.
      Electronic patient records were reviewed for patient tolerance of medication and
      serious adverse events. The primary study outcome was the frequency of serious
      adverse events. RESULTS: Available for analysis were 9359 patient records.
      Transient medication side effects were reported by 1447 (15.5%) patients. Severe
      adverse events were identified on 12 patients either during treatment with
      continuous subcutaneous terbutaline (n=4), or after discontinuation of outpatient
      treatment (n=8). The most frequent serious adverse event was pulmonary edema
      (n=9). There was no maternal mortality. CONCLUSION: Continuous subcutaneous
      terbutaline infusion was associated with an extremely low incidence of serious
      adverse events. Patients with comorbidities and/or concomitant tocolysis with
      intravenous magnesium sulfate should be closely assessed for development of
      serious adverse events.

PMID- 15507954
TI  - The effect of fetal behavioral states on middle cerebral artery peak systolic
      velocity.
AB  - OBJECTIVE: This study was undertaken to determine whether is there a difference
      in the middle cerebral artery peak systolic velocity (MCA PSV) between active and
      resting behavioral states in healthy fetuses aged 30 to 32 weeks. METHODS: MCA
      blood flow was measured by pulsed Doppler sonography 3 times during each fetal
      behavioral state (active and resting). The average during active state was
      compared during the resting state. Statistical analysis was performed by paired t
      test. RESULTS: During the fetal active state, there was a significant increase in
      the mean PSV (51.59 cm/s vs 46.95 cm/s, P < .0001) and mean end-diastolic
      velocity (9.59 cm/s vs 7.98 cm/s, P=.0015), and a significant decrease in the
      mean pulsatility index (PI) (2.07 vs 2.19, P=.0226) and the mean resistance index
      (0.83 vs 0.85, P=.0481). CONCLUSION: Healthy preterm fetuses have a significantly
      higher MCA PSV during the active state. Activity state should be considered when
      interpreting MCA Doppler indices.

PMID- 15507955
TI  - Training in chorionic villus sampling: limited experience for US fellows.
AB  - OBJECTIVE: This study was undertaken to assess training availability, methods,
      and plans for future practice of invasive procedures for maternal fetal medicine
      (MFM) fellows. STUDY DESIGN: A survey was sent to all MFM fellows registered with
      the American Board of Obstetrics and Gynecology in March of 2001. RESULTS: Of 91
      surveys, 55 (60.4%) were returned. All respondents were trained in second
      trimester amniocentesis and planned on performing the procedure after fellowship.
      Of the 55 respondents, 53 (96.4%) were trained on continuing pregnancies. Despite
      82% of training institutions performing chorionic villus sampling (CVS), only 24
      of 45 (53%) fellows had availability for training. Of those 24, 14 (58%)
      initiated training on pregnancies that were undergoing termination. Median number
      of procedures performed by fellows (continuing pregnancies and before
      termination) was 3 (range 0-120), with 40 procedures (range 0-140) expected to be
      performed before completing fellowship. Twenty-eight fellows planned on
      performing CVS after training. CONCLUSION: The number of centers training MFM
      fellows in CVS and the number of procedures performed in the United States is
      limited.

PMID- 15507956
TI  - Nucleated red blood cells in concordant, appropriate-for-gestational age twins.
AB  - OBJECTIVES: The purpose of this study was to test the hypothesis that neonatal
      nucleated red blood cell (RBC) counts are elevated in nondiscordant twins
      compared with singletons. STUDY DESIGN: We compared absolute nucleated RBC counts
      taken after birth in 2 groups of term, appropriate-for-gestational age infants;
      74 concordant twins, and 29 singleton control infants. We excluded infants with
      factors associated with a potential increase in absolute nucleated RBC counts.
      RESULTS: Birth weight and gestational age were significantly lower in twins than
      in singletons (P < .01). Hematocrit, absolute nucleated RBC count, and corrected
      lymphocyte counts were significantly higher in twins (P < .01). In multiple
      regression, the significantly higher absolute nucleated RBC count in twins
      remained significantly higher even after taking into account gestational age and
      Apgar scores. CONCLUSION: Concordant, appropriate-for-gestational age twins have
      increased nucleated RBCs at birth compared with singleton control infants.

PMID- 15507957
TI  - Thromboprophylaxis and pregnancy: two randomized controlled pilot trials that
      used low-molecular-weight heparin.
AB  - OBJECTIVE: The purpose of this study was to conduct pilot studies for large
      randomized controlled trials to compare low-molecular-weight heparin with placebo
      for antenatal thromboprophylaxis (trial 1), and for thromboprophylaxis after
      cesarean delivery (trial 2). STUDY DESIGN: Multicenter randomized controlled
      trials (trial 1, 23 units; trial 2, 8 units) were conducted. Pregnant women at
      increased risk for thromboembolic disease were eligible for trial 1; women who
      underwent cesarean delivery were eligible for trial 2. The interventions were
      once daily injections of low-molecular-weight heparin or placebo. Primary
      outcomes were as follows: trial 1, confirmed symptomatic thromboembolic events
      and symptomatic osteoporotic fractures; trial 2, confirmed symptomatic
      thromboembolic events and wound complications. RESULTS: Sixteen women were
      recruited for trial 1; 1 woman in the placebo group had a symptomatic
      thromboembolic event. One hundred forty-one women were recruited for trial 2; 1
      woman in the low molecular weight heparin group had a symptomatic thromboembolic
      event. CONCLUSION: Poor recruitment indicates that large-scale trials using these
      designs would be difficult. Collection of data on the number of women that are
      eligible and the reasons for nonrecruitment in future trials of these
      interventions would allow a better understanding of the reasons for poor
      recruitment.

PMID- 15507958
TI  - Neonatal cerebral white matter injury in preterm infants is associated with
      culture positive infections and only rarely with metabolic acidosis.
AB  - OBJECTIVE: Neonatal cerebral white matter injury represents a major precursor for
      neurological impairment and cerebral palsy. Our objective was to identify risk
      factors associated with its development. STUDY DESIGN: This retrospective case
      control study of all births between 23 and 34 weeks gestation at a single
      university hospital between May 1994 and September 2001 identified 150 cases with
      white matter injury characterized by periventricular leukomalacia or ventricular
      dilatation from white matter atrophy that were chromosomally normal and did not
      have other congenital anomalies. Cases were matched to controls without brain
      injury by the next delivery within 7 days of their gestational age. RESULTS:
      There were small differences between controls and cases in gestational age (27.5
      +/- 2.7, 27.4 +/- 2.6 weeks, P = .01) and birth weight (1053 +/- 402, 966 +/- 285
      g, P = .002) that were statistically but not clinically significant. There was no
      difference in the percentage of controls and cases delivered by cesarean (45%,
      49%, P = .64). There were no differences between controls and cases in umbilical
      arterial pH (7.27 +/- 0.11, 7.25 +/- 0.15, P = .19), base excess (-2.1 +/- 2.7, 
      3.0 +/- 4.1 mmol/L, P = .28), pH less than 7.0 (2/122 [2%], 3/107 [3%], P = 1.0),
      or base excess less than -12 mmol/L (4/121 [3%], 6/106 [6%], P = .75). The cases
      had a significant increase in positive blood (19%, 29%, P = .036), cerebrospinal
      fluid (6%, 17%, P = .002), and tracheal (9%, 22%, P = .003) cultures during the
      neonatal period. Conditional logistic regression showed a significant association
      among multiple gestations ( P = .02), intraventricular hemorrhage ( P < .001),
      and positive tracheal cultures ( P = .02) with cerebral white matter injury.
      CONCLUSION: Culture-positive infection was associated with an increased risk of
      cerebral white matter injury in preterm neonates. Intrapartum hypoxia-ischemia as
      manifested by metabolic acidosis was rarely associated with white matter injury
      and was not different from the incidence in premature neonates without injury.

PMID- 15507959
TI  - Cerclage for prevention of preterm birth in women with a short cervix found on
      transvaginal ultrasound examination: a randomized trial.
AB  - OBJECTIVE: The purpose of this study was to determine the efficacy of cerclage
      and bed rest versus bed rest-only for the prevention of preterm birth in women
      with a short cervix found on transvaginal ultrasound examination. STUDY DESIGN:
      Women with > or =1 of high-risk factors for preterm birth (> or =1 preterm birth
      at < 35 weeks of gestation, > or =2 curettages, diethylstilbestrol exposure, cone
      biopsy, Mullerian anomaly, or twin gestation) were screened with transvaginal
      ultrasonography of the cervix every 2 weeks from 14 weeks of gestation to 23
      weeks 6 days of gestation. Enrollment was offered to both asymptomatic women who
      were at high risk and who were identified to have short cervix (< 25 mm) or
      significant funneling (>25%) and nonscreened women who were at low risk and who
      were identified incidentally. The women who gave written consent were assigned
      randomly to receive either McDonald cerclage or bed rest-only. Both groups
      received similar counseling and treatment. Primary outcome was preterm birth at <
      35 weeks of gestation. RESULTS: Sixty-one women were assigned randomly. Forty
      seven pregnancies (77%) were high-risk singleton gestations. Thirty-one women
      (51%) were allocated to cerclage, and 30 women (49%) were allocated to bed rest.
      There were no differences between the groups in demographic characteristics, risk
      factors, and cervical variables. Preterm birth at < 35 weeks of gestation
      occurred in 14 women (45%) in the cerclage group and in 14 women (47%) in the bed
      rest group (relative risk, 0.94; 95% CI, 0.34-2.58). There was no difference in
      any obstetric or neonatal outcomes. A subanalysis of singleton pregnancies with
      previous preterm birth at < 35 weeks of gestation and a short cervix of < 25 mm
      (n = 31 women) also revealed no significant difference in recurrent preterm birth
      at < 35 weeks of gestation (40% vs 56%; relative risk, 0.52; 95% CI, 0.12-2.17).
      CONCLUSION: Cerclage did not prevent preterm birth in women with a short cervix.
      These results should be confirmed by larger trials.

PMID- 15507960
TI  - Fetal interleukin-1 receptor antagonist gene polymorphism, intra-amniotic
      interleukin-1beta levels, and history of spontaneous abortion.
AB  - OBJECTIVE: The purpose of this study was to determine whether fetal carriage of
      specific alleles of the polymorphic interleukin-1 receptor antagonist gene is
      associated with variations in intra-amniotic cytokine levels and previous
      pregnancy outcomes. STUDY DESIGN: Fetal cells in midtrimester amniotic fluid from
      189 women were tested for interleukin-1 receptor antagonist intron 2 length
      polymorphisms. Concentrations of cytokines in amniotic fluid were tested by
      enzyme-linked immunosorbent assay. Pregnancy history data were obtained
      subsequently. RESULTS: Homozygosity for interleukin-1 receptor antagonist allele
      1 was detected in 13 of 17 fetuses (76.5%) from women whose previous pregnancies
      all ended in spontaneous abortions, as compared with 33 of 74 fetuses (44.6%)
      from women with at least 1 previous term birth ( P = .02). Fetal carriage of
      interleukin-1 receptor antagonist allele 2 was associated with only 1 (5.9%)
      previous spontaneous abortion, as opposed to 31 pregnancies (41.9%) that were
      associated with a previous term delivery ( P = .004). A similar relationship
      between interleukin-1 receptor antagonist allele 1 and spontaneous abortions was
      observed when pregnancies of white women only were analyzed. Median mid trimester
      amniotic fluid interleukin-1beta concentrations were higher in women whose
      previous pregnancies ended in term deliveries (15.7 pg/mL), as opposed to women
      with 1 to 2 (6.4 pg/mL; P = .04) or > or =3 (4.1 pg/mL; P = .007) previous
      spontaneous abortions. Fetal carriage of interleukin-1 receptor antagonist allele
      2 was associated with elevated intra-amniotic interleukin-1beta levels (16.2
      pg/mL), as compared with interleukin-1 receptor antagonist allele 1 homozygotes
      (10.8 pg/mL; P = .03). CONCLUSION: Fetal carriage of interleukin-1 receptor
      antagonist allele 1 is associated with reduced intra-amniotic interleukin-1beta
      concentrations and an increased occurrence of spontaneous abortions in previous
      pregnancies.

PMID- 15507961
TI  - Polymorphism in intron 2 of the interleukin-1 receptor antagonist gene, local
      midtrimester cytokine response to vaginal flora, and subsequent preterm birth.
AB  - OBJECTIVE: This study investigated the association between polymorphism in intron
      2 of the interleukin-1 receptor antagonist gene, midtrimester vaginal microflora,
      vaginal interleukin receptor antagonist and interleukin-1beta levels and
      subsequent spontaneous preterm birth. STUDY DESIGN: Vaginal samples from 212
      women, collected at 18-22 weeks' gestation, were analyzed for the polymorphism in
      intron 2 of the interleukin-1 receptor antagonist gene by polymerase chain
      reaction, qualitative and quantitative vaginal microflora, and interleukin-1beta
      and interleukin-1ra concentrations by enzyme-linked immunosorbent assay.
      Pregnancy outcome data were subsequently obtained. RESULTS: Carriage of intron 2
      of the interleukin-1 receptor antagonist allele 2 (IL1RN * 2) was associated with
      an elevated vaginal pH in black ( P < .001) and white ( P = .005) women, a
      reduced interleukin-1beta response to anaerobic Gram-negative rods and/or
      Gardnerella vaginalis ( P < .01), and a decreased rate of spontaneous preterm
      deliveries (6% versus 18%, P = .02). In black women, IL1RN * 2 carriage was
      associated with increased anaerobic Gram-negative rods, Mycoplasma, and
      Peptostreptococci and decreased Lactobacilli colonization. CONCLUSION: IL1RN * 2
      carriage was associated with a blunted proinflammatory interleukin-1beta response
      to abnormal vaginal flora. This property may decrease susceptibility to infection
      related preterm birth.

PMID- 15507962
TI  - Genome-wide expression profiling of fetal membranes reveals a deficient
      expression of proteinase inhibitor 3 in premature rupture of membranes.
AB  - OBJECTIVE: We used a genome-wide approach to identify differentially expressed
      genes in patients with preterm premature rupture of membranes to improve the
      understanding of underlying molecular mechanisms. STUDY DESIGN: RNA was isolated
      from the fetal membranes of patients with preterm labor with intact membranes and
      preterm premature rupture of membranes and was stratified according to the
      presence or absence of histologic chorioamnionitis. Microarray experiments were
      used to identify differentially expressed genes, and real-time quantitative
      reverse transcriptase-polymerase chain reaction and immunohistochemistry were
      used in follow-up experiments. RESULTS: Microarray experiments identified
      decreased expression of proteinase inhibitor 3 in the preterm premature rupture
      of membranes cases. Quantitative reverse transcriptase-polymerase chain reaction
      confirmed these results. Immunohistochemistry demonstrated decreased proteinase
      inhibitor 3 protein expression in preterm premature rupture of membranes.
      CONCLUSION: A genome-wide approach identified deficient expression of proteinase
      inhibitor 3 in preterm premature rupture of membranes, which demonstrated the
      usefulness of functional genomics for the dissection of mechanisms of disease and
      identification of differentially regulated genes that were not suspected
      previously to play a role in parturition.

PMID- 15507963
TI  - Clinical significance of intra-amniotic inflammation in patients with preterm
      premature rupture of membranes.
AB  - OBJECTIVE: This study was conducted to determine the frequency and clinical
      significance of intra-amniotic inflammation in patients with preterm premature
      rupture of the membranes. STUDY DESIGN: Amniotic fluid was retrieved from 219
      patients with preterm premature rupture of the membranes; the fluid was cultured
      for aerobic and anaerobic bacteria and mycoplasmas and assayed for neutrophil
      collagenase, which is also known as matrix metalloproteinase-8. Matrix
      metalloproteinase-8 was used because previous studies indicated that this was a
      sensitive and specific index of inflammation and that is correlated with the
      amniotic fluid white blood cell count. Intra-amniotic inflammation was defined as
      an elevated amniotic fluid matrix metalloproteinase-8 concentration (>23 ng/mL).
      Nonparametric and survival techniques were used for statistical analysis.
      RESULTS: The overall rate of intra-amniotic inflammation was 42% (93/219
      samples); proven intra-amniotic infection was detected only in 23% (50/219
      samples). Intra-amniotic inflammation with a negative amniotic fluid culture for
      micro-organisms was found in 23% (51/219 samples) and was as common as proven
      intra-amniotic infection. Pregnancy outcome was worse in patients with intra
      amniotic inflammation and a negative culture than in those patients with a
      negative culture and without inflammation. There were no differences in the
      interval-to-delivery or rate of complications between patients with intra
      amniotic inflammation and a negative culture and patients with proven amniotic
      fluid infection. CONCLUSION: We conclude that intra-amniotic inflammation,
      regardless of culture result, is present in 42% of patients with preterm
      premature rupture of the membranes and that it is a risk factor for impending
      preterm delivery and adverse outcome. We propose that intra-amniotic
      inflammation, rather than infection, be used to classify and treat patients with
      preterm premature rupture of the membranes.

PMID- 15507964
TI  - Toll-like receptor-2 and -4 in the chorioamniotic membranes in spontaneous labor
      at term and in preterm parturition that are associated with chorioamnionitis.
AB  - OBJECTIVE: The Toll-like receptor-2 and -4 recognize microbial products that are
      associated with gram-positive and gram-negative bacteria, respectively. This
      study examined Toll-like receptor-2 and -4 expression in fetal membranes in
      response to labor at term and histologic chorioamnionitis. STUDY DESIGN:
      Immunohistochemistry and real-time quantitative reverse transcriptase-polymerase
      chain reaction were used to examine the chorioamnion from patients with (1)
      preterm labor and intact membranes, (2) preterm premature rupture of membranes
      who were delivered < or =34 weeks of gestation, and (3) women at term with or
      without labor. All groups were stratified on the basis of the presence of
      histologic chorioamnionitis. RESULTS: Toll-like receptor-2 expression was
      significantly higher in patients with chorioamnionitis than in patients without
      this condition (all P < .05). The Toll-like receptor-2 and -4 messenger RNA
      amounts were significantly higher in membranes from women at term with
      spontaneous labor than women who were not in labor ( P = .001 and .002,
      respectively). Toll-like receptor-2 expression was polarized to the basal surface
      of amniotic epithelial cells in patients without chorioamnionitis, but this
      distribution was lost in the presence of inflammation. CONCLUSION: Spontaneous
      labor at term and preterm delivery with histologic chorioamnionitis, regardless
      of the membrane status (intact or ruptured), are associated with an increased
      expression of Toll-like receptor-2 and -4 in the chorioamniotic membranes. These
      observations have implications for understanding the biologic nature of innate
      immunity.

PMID- 15507965
TI  - Induction of premature labor and delivery by allergic reaction and prevention by
      histamine H1 receptor antagonist.
AB  - OBJECTIVE: The purpose of this study was to determine whether type I
      hypersensitivity can induce preterm labor and delivery that may be prevented by
      the administration of an H 1 receptor antagonist or a mast-cell stabilizer. STUDY
      DESIGN: At days 40 through 50 of gestation, ovalbumin-sensitized guinea pigs that
      had not been treated or had been pretreated with an H 1 receptor antagonist
      (ketotifen) or a mast-cell stabilizer (cromolyn sodium) were challenged with
      either ovalbumin or saline solution. Nonsensitized guinea pigs were challenged
      with ovalbumin. RESULTS: The duration of gestation was significantly shorter in
      sensitized animals that were challenged with ovalbumin than in the other groups.
      Pretreatment with ketotifen significantly increased the duration of pregnancy in
      sensitized animals, compared with untreated animals. Cromolyn sodium had no
      effect. CONCLUSION: An allergic reaction can induce premature labor/delivery, and
      pretreatment with histamine H 1 receptor antagonist can prevent it. These
      observations provide evidence of a novel mechanism of disease for premature labor
      and delivery.

PMID- 15507966
TI  - Adverse outcomes after preterm labor are associated with tumor necrosis factor
      alpha polymorphism -863, but not -308, in mother-infant pairs.
AB  - OBJECTIVE: Two single-base polymorphisms of the tumor necrosis factor-alpha gene
      (TNF-alpha) at positions -863 and -308 are associated with variation in
      production of TNF-alpha (TNF-alpha). TNF-alpha genotypes were tested for
      association with adverse outcomes in mother-infant pairs with preterm labor.
      STUDY DESIGN: We analyzed a cohort of 118 mother-infant pairs with preterm labor
      before 34 weeks' gestation. Polymerase chain reaction was used on extracted
      deoxyribonucleic acid for polymorphism assay. Outcomes included amniotic fluid
      TNF-alpha concentration, histologic chorioamnionitis, delivery gestational age,
      and composite neonatal morbidity. Statistical significance was determined by chi
      2 and Kruskal-Wallis analysis of variance. RESULTS: Mothers homozygous for the 
      863 polymorphism (AA) had significantly earlier deliveries ( P = .02), more
      chorioamnionitis ( P = .03), and greater composite neonatal morbidity ( P = .03).
      Neither maternal nor fetal carriage of the -308 polymorphism was associated with
      adverse outcome. CONCLUSION: In women with preterm labor before 34 weeks'
      gestation, maternal homozygous carriage of the -863 polymorphism may be
      associated with preterm delivery and adverse neonatal outcome.

PMID- 15507967
TI  - Polymorphisms in the tumor necrosis factor-alpha gene at position -308 and the
      inducible 70 kd heat shock protein gene at position +1267 in multifetal
      pregnancies and preterm premature rupture of fetal membranes.
AB  - OBJECTIVE: The purpose of this study was to determine the relationship between
      preterm premature rupture of membranes, tumor necrosis factor-alpha, and heat
      shock protein-70 gene polymorphisms in multifetal gestations. STUDY DESIGN:
      Buccal swabs from 101 mother-neonate pairs of multifetal pregnancies were tested
      for single nucleotide polymorphisms at position -308 of the tumor necrosis factor
      alpha gene and +1267 of the heat shock protein-70 gene. Pregnancy outcome data
      were obtained subsequently. RESULTS: Tumor necrosis factor-alpha allele 2
      carriage by the first-born occurred in 10 of 27 pregnancies (37.0%) that resulted
      in preterm premature rupture of membranes compared with 6 of 67 pregnancies
      (9.0%) without preterm premature rupture of membranes ( P = .002). The allele
      frequency of tumor necrosis factor-alpha allele 2 and heat shock protein-70
      allele 2 in the first born was higher in pregnancies that were complicated by
      preterm premature rupture of membranes (18.5% vs 4.5%; P = .003; and 57.7% vs
      41.3%; P = .04, respectively). There was no relationship between tumor necrosis
      factor-alpha allele 2 or heat shock protein-70 allele 2 carriage by the second
      fetus or mother and preterm premature rupture of membranes. CONCLUSION: Tumor
      necrosis factor-alpha allele 2 and/or heat shock protein-70 allele 2 carriage by
      the first-born fetus is associated with preterm premature rupture of membranes in
      multifetal pregnancies.

PMID- 15507968
TI  - Umbilical cord plasma interleukin-6 concentrations in preterm infants and risk of
      neonatal morbidity.
AB  - OBJECTIVE: This study was undertaken to evaluate the association between
      umbilical cord interleukin-6 (IL-6) levels and neonatal morbidity in infants born
      at less than 32 weeks' gestation. STUDY DESIGN: Umbilical cord plasma IL-6 levels
      and neonatal outcomes were assessed in 309 infants born between 24 weeks and 0
      days' and 31 weeks and 6 days' gestation. RESULTS: Mean IL-6 levels were higher
      in spontaneous (n = 193, 355 +/- 1822 pg/mL) compared with indicated preterm
      births (n = 116, 37 +/- 223 pg/mL, P < .0001). Adjusting for gestational age, a
      progressive relationship was noted between increasing IL-6 levels and increased
      risk of neonatal systemic inflammatory response syndrome (SIRS). IL-6 levels
      beyond the 90th percentile (> or =516.6 pg/mL) were also significantly associated
      with periventricular leukomalacia (PVL; odds ratio [OR] 15, 95% CI 2-149) and
      necrotizing enterocolitis (NEC; OR 6, 95% CI 1.1-33). In the multivariate
      analysis, an IL-6 level 107.7 pg/mL or greater (determined by receiver operating
      curve analysis) remained a significant independent risk factor for PVL (OR 30.3,
      95% CI 4.5-203.6). CONCLUSION: Umbilical cord IL-6 levels are higher in preterm
      infants born after spontaneous preterm labor or premature rupture of membranes.
      Elevated IL-6 levels are associated with an increased risk for SIRS, PVL, and NEC
      in infants born at less than 32 weeks' gestation.

PMID- 15507969
TI  - Mycoplasma hominis and Ureaplasma urealyticum in midtrimester amniotic fluid:
      association with amniotic fluid cytokine levels and pregnancy outcome.
AB  - OBJECTIVE: The association between the detection of Mycoplasma hominis or
      Ureaplasma urealyticum in midtrimester amniotic fluid and amniotic fluid cytokine
      concentrations and subsequent pregnancy outcome were examined. STUDY DESIGN:
      Amniocentesis was performed between 15 and 19 weeks of gestation in 179
      asymptomatic women. Aliquots were assayed for M hominis and U urealyticum by
      polymerase chain reaction coupled to enzyme-linked immunosorbent assay. Intra
      amniotic levels of interleukin-1beta, interleukin-1 receptor antagonist,
      interleukin-4, interleukin-6, and tumor necrosis factor-alpha were determined by
      enzyme-linked immunosorbent assay. Pregnancy outcomes were obtained after the
      completion of all testing. RESULTS: U urealyticum was detected in 22 of 172
      amniotic fluids (12.8%); M hominis was present in 11 of 179 amniotic fluids
      (6.1%). There was no relationship between U urealyticum detection and the
      concentration of any cytokine. Detection of M hominis was associated with
      elevated intra-amniotic concentrations of interleukin-4 ( P = .01). Preterm
      premature rupture of membranes that was followed by preterm birth occurred in 5
      women (2.8%); 5 women (2.8%) had a spontaneous preterm birth with intact
      membranes. All 5 of the women with preterm premature rupture of membranes (100%)
      tested positive for either U urealyticum or M hominis , as opposed to none of the
      women with spontaneous preterm birth and to 27 of 161 women (16.8%) with a term
      birth ( P = .0002). CONCLUSION: The detection of M hominis or U urealyticum in
      midtrimester amniotic fluid by polymerase chain reaction-enzyme-linked
      immunosorbent assay may be a risk factor for subsequent preterm premature rupture
      of membranes.

PMID- 15507970
TI  - Maternal infection-induced white matter injury is reduced by treatment with
      interleukin-10.
AB  - OBJECTIVE: The purpose of this study was to test the hypothesis that interleukin
      10 can prevent white matter injury in neonatal rats that are born to infected
      dams. STUDY DESIGN: Timed pregnant rats (day 17) were assigned to the following
      treatment groups: (1) saline control (n = 5 rats), (2) Escherichia coli- infected
      (n = 10 rats), and (3) E coli + interleukin-10 (n = 5 rats). E coli was
      administered at a titer of 1 x 10(7) colony-forming units by intrauterine
      inoculation just above the cervix at the bifurcation of the uterine horns. Rat
      interleukin-10 was administered intravenously at a dose of 1 microg/kg of body
      weight. After delivery, the pups were maintained with dams until day 8, at which
      time they were placed under general anesthesia and perfused with saline solution
      followed by 10% paraformaldehyde. The brains were removed, placed in 30% sucrose
      solution, and then frozen at -20 degrees C until the preparation of the frozen
      sections. Standard hematoxylin/eosin staining was performed, and the brains were
      evaluated for matter necrosis, apoptotic cells, and ventricular swelling.
      RESULTS: In pups that were born to infected dams, 11 of 38 pups (29%) displayed
      symmetric lesions around the lateral ventricles. These lesions were characterized
      by marked looseness/edema of the neuropil, foamy-appearing histiocytes, and
      granular neuropil breakdown. None of the pups (n = 17) that were born to
      interleukin-10-treated infected dams displayed this pattern of severe white
      matter injury. CONCLUSION: These results suggest that maternal interleukin-10
      therapy could provide neuroprotection for infants who are born to mothers with
      intrauterine infection.

PMID- 15507971
TI  - Prior cone biopsy: prediction of preterm birth by cervical ultrasound.
AB  - OBJECTIVE: This study was undertaken to determine the predictive accuracy for
      preterm birth of transvaginal ultrasound (TVU) of the cervix in women with a
      prior cone biopsy. STUDY DESIGN: Pregnant patients with a history of cervical
      cone biopsy by cold knife, loop electrosurgical excision procedure (LEEP), or
      laser were monitored prospectively with TVU of the cervix between 16 and 24
      weeks. The predictive value of TVU was evaluated by using less than 25 mm
      cervical length as criteria for the definition of a short cervix. The primary
      outcome was spontaneous preterm birth less than 35 weeks. RESULTS: Of 109 women
      with prior cone biopsy identified, 55 had LEEP, 45 cold knife, and 9 laser cone
      biopsies. Thirty (28%) had a short cervix, with 9 (30%) having spontaneous
      preterm birth less than 35 weeks. Seventy-nine (72%) did not have a short cervix,
      with 5 (6%) having spontaneous preterm birth less than 35 weeks. The sensitivity,
      specificity, and positive and negative predictive values for spontaneous preterm
      birth were 64%, 78%, 30%, and 94%, respectively (relative risk [RR] 4.7, 95% CI
      1.6-15.3). CONCLUSION: TVU of the cervix is predictive of preterm birth in women
      with prior cone biopsy.

PMID- 15507972
TI  - Perinatal intervention and neonatal outcomes near the limit of viability.
AB  - OBJECTIVE: The purpose of this study was to evaluate trends in the level of
      obstetric and neonatal intervention near the limit of viability and perinatal
      morbidity and mortality rates over time. STUDY DESIGN: In this retrospective
      chart review, live-born infants who were delivered at 23 to 26 weeks of gestation
      and who weighed between 500 and 1500 g between 1990 and 2001 in an urban tertiary
      care center were identified. Maternal charts were reviewed for clinical
      characteristics and antenatal and intrapartum course. Neonatal charts were
      reviewed for short-term morbidities that included respiratory distress syndrome,
      intraventricular hemorrhage, necrotizing enterocolitis, retinopathy of
      prematurity, and survival. The study group was divided into 2 cohorts (group
      I:1990-95; group II:1996-2001); the obstetrician's willingness to intervene,
      neonatal resuscitation efforts, infant mortality (in gestational age subgroups)
      rate, and short-term morbidity rate were compared. Multivariate analyses, which
      controlled for obstetrician willingness to intervene, neonatal resuscitation,
      cohort, and gestational age, were performed to evaluate infant survival in the
      entire cohort and for morbidity in the survivors. RESULTS: Records for 260
      mothers and 293 newborn infants were evaluated. Comparing the 2 cohorts (group I
      vs II), we found increases over time in intent to intervene for fetal indication
      (70% vs 89%; P = .0007), cesarean delivery for malpresentation (20% vs 42%; P =
      .0003), and survival (54% vs 70%; P = .003). Pregnancies in group 1 were less
      likely to have received antenatal steroids (7.7% vs 60%) or surfactant (39% vs
      73%; P <.0001 for each). Survival increased with advancing delivery gestation
      (24%, 51%, 68%, and 85% at 23, 24, 25, and 26 weeks of gestation, respectively; P
      <.0001). However, among survivors, the incidences of necrotizing enterocolitis,
      retinopathy of prematurity, intraventricular hemorrhage, respiratory distress
      syndrome, sepsis, and bronchopulmonary dysplasia did not decline significantly
      with advancing gestational age, after controlling for other factors. CONCLUSION:
      Obstetric intervention and aggressive neonatal resuscitation have increased for
      pregnancies delivered between 23 and 26 weeks of gestation over the past decade.
      Although survival has increased over time and with advancing gestational age at
      delivery, short-term morbidity in survivors is similar, regardless of gestational
      age in this cohort. A brief delay in delivery of those pregnancies who are at
      risk for delivery between 23 and 26 weeks of gestation may improve survival,
      although short-term morbidity in survivors will not be affected substantially.

PMID- 15507973
TI  - Characterization of corticosteroid redosing in an in vitro cell line model.
AB  - OBJECTIVE: The purpose of this study was to investigate dexamethasone redosing as
      function of time and dose. STUDY DESIGN: We studied the effect of 48 hours'
      exposure to various concentrations of dexamethasone in a human pulmonary
      adenocarcinoma cell line (H-441). We measured the level of surfactant protein B
      (SP-B) mRNA by quantitative reverse transcription-PCR after initial dexamethasone
      exposure, and after redosing, 1 or 2 weeks later. Values are mean +/- SE for 5
      experiments. Comparisons were made by Mann-Whitney and Kruskal-Wallis test with
      significance set at P < .05. RESULTS: Induction of SP-B mRNA was maximal within
      48 hours of the initial dexamethasone exposure. Redosing with the same
      dexamethasone concentration resulted in levels more than double those initially
      observed. Redosing with dexamethasone concentration 10 times lower had an effect
      comparable to that of the initial, higher concentration. CONCLUSION: Our results
      suggest a residual effect of the initial exposure that potentiates redosing,
      allowing significant dose reductions.

PMID- 15507974
TI  - The effects of the time interval from antenatal corticosteroid exposure to
      delivery on neonatal outcome of very low birth weight infants.
AB  - OBJECTIVE: The purpose of this study was to determine whether the interval
      between antenatal steroid exposure and delivery influences neonatal outcome in
      very low birth weight infants. STUDY DESIGN: A retrospective review was performed
      of all live-born singleton infants who weighed between 500 and 1500 g and who
      were exposed to a partial course (1 dose) or a complete course (2 12-mg doses of
      betamethasone given 24 hours apart) of antenatal corticosteroids. Infants were
      divided into 4 groups, depending on the interval between the first dose of
      antenatal corticosteroids and delivery (<24 hours, between 24 and 48 hours,
      between 48 hours and 7 days, and >7 days). Logistic regression was used to
      control for differences between the 4 groups. RESULTS: Three hundred twenty-five
      singleton deliveries were reviewed. Gestational age at delivery and birth weight
      were similar for all 4 groups. The babies in the last group were treated with
      antenatal corticosteroids at a slightly earlier gestational age. There was no
      statistical difference between the groups with respect to respiratory distress
      syndrome treated with surfactant, intraventricular hemorrhage, necrotizing
      enterocolitis, and deaths. CONCLUSION: In infants who weighed 500 to 1500 g, the
      time interval between exposure to antenatal corticosteroids and delivery does not
      appear to affect neonatal outcome. Further studies should evaluate the effects of
      antenatal corticosteroids and the effects of the interval from exposure to
      delivery in very low birth weight infants.

PMID- 15507975
TI  - The association between hyaline membrane disease and preeclampsia.
AB  - OBJECTIVE: The purpose of this study was to determine whether hyaline membrane
      disease is increased in newborn infants who are born to women with preeclampsia
      compared with control subjects. STUDY DESIGN: This was a historic cohort study of
      deliveries between 24 and 37 weeks of gestation at the Medical University of
      South Carolina from 1996 through 2002. Singleton infants who were born to women
      with preeclampsia were compared with nonpreeclamptic control subjects. The
      incidence of hyaline membrane disease was compared by chi 2 analysis and Fisher
      exact test, with significance at a probability value of <.05. Logistic regression
      analysis was performed to address potential confounders. RESULTS: There were 814
      women with preeclampsia and 3021 control subjects. When we controlled for
      confounding factors, there was a significant increase in the incidence of hyaline
      membrane disease in the preeclamptic group overall (odds ratio, 1.35; 95% CI,
      1.03-1.78). The risk was more pronounced in neonates who were born at 32 weeks of
      gestation (odds ratio, 1.93; 95% CI, 1.28-2.91). CONCLUSION: The risk of hyaline
      membrane disease in neonates at < 32 weeks of gestation is increased in patients
      with preeclampsia. This supports the contention that fetal lung maturity is not
      accelerated in preeclampsia.

PMID- 15507976
TI  - Elevated plasma endothelial microparticles: preeclampsia versus gestational
      hypertension.
AB  - OBJECTIVE: Elevated plasma endothelial microparticle levels have been found to be
      elevated in women with preeclampsia. However, their role in distinguishing
      preeclampsia from gestational hypertension remains to be elucidated. The
      objectives of this study were to compare endothelial microparticle levels among
      patients with preeclampsia, gestational hypertension, and healthy pregnant
      control subjects and to evaluate the effect of plasma from women with
      preeclampsia and gestational hypertension on the release of endothelial
      microparticles by renal microvascular endothelial cells. STUDY DESIGN: A
      prospective study was conducted on 52 women with preeclampsia, 20 women with
      gestational hypertension, and 38 healthy pregnant control subjects. Endothelial
      microparticles were measured by flow cytometry with fluorescent monoclonal mouse
      anti-human antibodies against CD31, CD42b, and CD62E. RESULTS: CD31 + /42b -
      endothelial microparticle levels were 10497 +/- 5145 counts/microL in women with
      preeclampsia versus 6768 +/- 1810 counts/microL in women with gestational
      hypertension ( P < .01). In control subjects, CD31 + /42b - endothelial
      microparticle levels were 6119 +/- 3592 counts/microL. CD62E + endothelial
      microparticle levels were 1930 +/- 966 counts/microL in women with preeclampsia
      versus 822 +/- 150 counts/microL in women with gestational hypertension ( P
      <.01). In control subjects, CD62E + endothelial microparticle levels were 712 +/-
      160 counts/microL. Incubation of renal microvascular endothelial cells with
      plasma from women with preeclampsia resulted in a rise in CD31 + and CD62E +
      endothelial microparticle levels as compared with women with gestational
      hypertension and control subjects. CONCLUSION: Endothelial microparticle levels
      are higher in women with preeclampsia than in women with gestational hypertension
      and control subjects. The measurement of endothelial microparticles may be useful
      as a diagnostic tool for preeclampsia in pregnant women.

PMID- 15507977
TI  - Increased cerebral blood flow in preeclampsia with magnetic resonance imaging.
AB  - OBJECTIVE: The purpose of this study was to compare third trimester and
      nonpregnant cerebral blood flow of women with preeclampsia to normotensive
      control subjects with the use of magnetic resonance imaging techniques. STUDY
      DESIGN: Nine normotensive pregnant women and 12 untreated women with preeclampsia
      underwent velocity-encoded phase contrast magnetic resonance imaging of the
      bilateral middle and posterior cerebral arteries in the third trimester and at 6
      to 8 weeks after delivery. The Student t test was used for comparison, with a
      probability value of <.05 considered significant. RESULTS: Third-trimester large
      cerebral artery blood flow was significantly higher in preeclampsia. Mean vessel
      diameter was unchanged, except for the left posterior cerebral artery. There was
      no difference in mean vessel diameter or cerebral blood flow between the 2 groups
      while the women were not pregnant. CONCLUSION: Cerebral blood flow is increased
      significantly in preeclampsia. We hypothesize that increased cerebral blood flow
      ultimately could lead to eclampsia through hyperperfusion and the development of
      vasogenic edema.

PMID- 15507978
TI  - Reproductive outcomes after pregnancy complicated by maternal-fetal surgery.
AB  - OBJECTIVE: The reproductive outcomes for women after the pregnancy complicated by
      maternal-fetal surgery were evaluated to obtain evidence-based information for
      prenatal risk counseling. STUDY DESIGN: The retrospective review identified 83
      women with maternal-fetal surgery from a single institution (1996-2002). These
      women were sent a consent form and a questionnaire to document postoperative
      problems, fertility, obstetric outcomes, and psychosocial concerns in pregnancy
      after the index fetal therapy. Institutional Review Board approval was obtained
      from Committee for Protection of Human Subjects. RESULTS: The total return rate
      was 55 (66%). The pregnancy rate was 62% (18% spontaneous abortion, 24% preterm
      delivery, and 58% term delivery). Complications were reported in 12 of 34
      pregnancies (35%), including uterine dehiscence/rupture (12%/6%), cesarean
      hysterectomy (3%), and antepartum hemorrhage requiring transfusion (9%).
      CONCLUSION: The reproductive outcome of uterine dehiscence, rupture, and
      hysterectomy was 12%, 6%, and 3%, respectively, after a pregnancy complicated by
      maternal-fetal surgery. The uterine rupture rate is similar to the rupture rate
      after "classical" cesarean section (4%-9%).

PMID- 15507979
TI  - Clinical significance of first trimester crown-rump length disparity in
      dichorionic twin gestations.
AB  - OBJECTIVE: The purpose of this study was to determine the clinical significance
      of first trimester crown-rump disparity in dichorionic twin gestations. STUDY
      DESIGN: Ultrasound examinations of dichorionic twin pregnancies between 11 and 14
      weeks of gestation were evaluated for growth discordance using crown-rump length.
      Medical records were reviewed for antenatal complications that included
      spontaneous abortion, fetal death, fetal structural or chromosomal anomalies, and
      preterm delivery. Fisher's exact test was used for statistical analysis; a
      probability value of <.05 was considered significant. RESULTS: Of 159 twin
      pregnancies, there were 7 fetal structural anomalies, 2 fetal chromosomal
      anomalies, 5 second-trimester spontaneous abortions, 3 second-trimester fetal
      deaths, and 1 third-trimester fetal death. Pregnancies that were complicated by
      fetal structural or chromosomal anomalies had significantly greater median crown
      rump length discordance than pregnancies without fetal anomalies (4.0 mm vs 2.0
      mm; P = .02). Crown-rump length discordance >10%, which is the 90th percentile
      for intertwin crown-rump length disparity in our population, was associated with
      a significantly higher incidence of fetal anomalies (22.2% vs 2.8%; P = .01).
      CONCLUSION: First trimester crown-rump length disparity in dichorionic twin
      gestations is associated with an increased risk of fetal structural and
      chromosomal anomalies.

PMID- 15507980
TI  - Preterm twins: what threshold of birth weight discordance heralds major adverse
      neonatal outcome?
AB  - OBJECTIVE: This study was undertaken to establish the optimal threshold of birth
      weight discordance for prediction of adverse outcome in liveborn, non-malformed
      preterm twins. STUDY DESIGN: We accessed a cohort of twin gestations for the
      period 1990 through 2000 delivered at less than 37.0 weeks' gestation. Adverse
      neonatal outcome was defined as stillbirth or occurrence of major morbidities.
      RESULTS: A total of 335 twin gestations (670 twins) were included, of which 104
      (31%) experienced adverse neonatal outcome. The average birth weight discordance
      was 12.4% +/- 10.6% versus 19.4% +/- 14.8% in those with good versus adverse
      outcome (P < .001). Birth weight discordance was a significant predictor of
      adverse neonatal outcome that was independent of gestational age at delivery,
      small for gestational age, and chorionicity. Receiver operating characteristic
      curve analysis suggested that optimal thresholds of birth weight discordance for
      clinical use should take into account gestational age. CONCLUSION: Birth weight
      discordance is an independent predictor of adverse neonatal outcome in liveborn,
      non-malformed preterm twins.

PMID- 15507981
TI  - First-trimester maternal serum PAPP-A and free-beta subunit human chorionic
      gonadotropin concentrations and nuchal translucency are associated with obstetric
      complications: a population-based screening study (the FASTER Trial).
AB  - OBJECTIVE: The purpose of this study was to determine whether maternal serum
      levels of pregnancy-associated plasma protein A, free-beta subunit human
      chorionic gonadotropin, or nuchal translucency size are associated with obstetric
      complications. STUDY DESIGN: Data were obtained from the First and Second
      Trimester Evaluation of Risk trial. Pregnancy-associated plasma protein A and
      free-beta subunit human chorionic gonadotropin levels were analyzed, and nuchal
      translucency was measured between 10 weeks 3 days and 13 weeks 6 days of
      gestation in 34,271 pregnancies. RESULTS: Women with pregnancy-associated plasma
      protein A of < or =5th percentile were significantly more likely to experience
      spontaneous fetal loss at < or =24 weeks of gestation, low birth weight,
      preeclampsia, gestational hypertension, preterm birth ( P < .001) and stillbirth,
      preterm premature rupture of membranes, and placental abruption ( P < .02).
      Nuchal translucency at > or =99th percentile and free-beta subunit human
      chorionic gonadotropin at < or =1st percentile were associated with an increased
      risk of spontaneous loss at < or =24 weeks of gestation (adjusted odds ratios,
      3.90, 3.62, respectively; P < .001). CONCLUSION: Low pregnancy-associated plasma
      protein A levels in the first trimester were associated strongly with a number of
      adverse pregnancy outcomes. Low free-beta subunit human chorionic gonadotropin
      levels and large nuchal translucency were both associated with early fetal loss.

PMID- 15507982
TI  - Association of extreme first-trimester free human chorionic gonadotropin-beta,
      pregnancy-associated plasma protein A, and nuchal translucency with intrauterine
      growth restriction and other adverse pregnancy outcomes.
AB  - OBJECTIVE: The purpose of this study was to determine the association between
      first-trimester trisomy 21 screening markers (free human chorionic gonadotropin
      beta [hCG], pregnancy-associated plasma protein A [PAPP-A], and nuchal
      translucency) and adverse pregnancy outcome. STUDY DESIGN: This was a cohort
      study of 8012 patients enrolled in a National Institute of Child Health and Human
      Development-sponsored study of first-trimester trisomy 21 and 18 screening.
      Trisomy 21 and 18 risk results and individual marker levels in unaffected
      pregnancies and pregnancies with adverse outcomes were evaluated. RESULTS: PAPP-A
      <1st percentile (OR 5.4, 95% CI 2.8-10.3) and PAPP-A <5th percentile (OR 2.7, 95%
      CI 1.9-3.9) and free beta-hCG <1st percentile (OR 2.7, 95% CI 1.3-5.9) were
      associated with increased risk of intrauterine growth restriction (IUGR) with
      positive predictive values of 24.1%, 14.1%, and 14.3%, respectively. PAPP-A <5th
      percentile (OR 2.3 95% CI 1.1-4.7) and nuchal translucency >99th percentile (OR
      3.5, 95% CI 1.1-11.3) were associated with increased risk of preterm delivery
      before 34 weeks. Increased risk at screening for trisomy 21 and 18 identified 16
      of the 29 other chromosomal abnormalities (55%). Low free beta-hCG, low PAPP-A,
      and increased nuchal translucency were all associated with an increased rate of
      fetal abnormality. CONCLUSION: Extreme values of first-trimester free beta-hCG,
      PAPP-A, and nuchal translucency are all associated with adverse outcomes. The
      especially high predictive value for IUGR of PAPP-A levels below the 1st
      percentile suggests that patients within this group may benefit from increased
      surveillance for this condition.

PMID- 15507983
TI  - Differences in fat and lean mass proportions in normal and growth-restricted
      fetuses.
AB  - OBJECTIVE: The purpose of this study was to assess fetal subcutaneous fat and
      lean mass areas as predictors of fetal growth restriction. STUDY DESIGN:
      Seventeen severe fetal growth-restricted (abdominal circumference, < 2 SD)
      fetuses and 20 control fetuses underwent ultrasound measurements of subcutaneous
      fat, lean mass, and standard biometry. Thigh subcutaneous fat and lean mass were
      measured on enlarged ultrasound axial images (subcutaneous fat area = total cross
      sectional area - lean mass area [bone + muscle areas]). Subcutaneous fat and lean
      mass areas were expressed as a percentage of the total cross-sectional area and
      were normalized to femur length and head circumference. Measurements were modeled
      as a function of fetal growth-restriction status and week of gestation with
      multiple linear regression. RESULTS: Fetal growth-restriction fetuses showed
      reductions in fat and lean mass (in standard biometry) and showed a
      disproportionate reduction in fat mass compared with lean mass. These were all
      associated significantly with fetal growth restriction. CONCLUSION: Fetal growth
      restricted fetuses have reduced subcutaneous fat and lean mass compared with
      control fetuses; a further reduction occurs in subcutaneous fat concentration
      compared with the reduction in lean mass when fat is normalized for body size,
      with either head circumference or femur length. Fat-to-bone proportions may be
      useful in distinguishing the small for gestational age fetus who is truly fetal
      growth restriction from the constitutionally small fetus.

PMID- 15507984
TI  - Abnormal multiple marker screens are associated with adverse perinatal outcomes
      in cases of intrauterine growth restriction.
AB  - OBJECTIVE: The purpose of this study was to determine if abnormal multiple marker
      screens (MMS) are associated with adverse perinatal outcomes in intrauterine
      growth restriction (IUGR) pregnancies. STUDY DESIGN: This was a case control
      study of IUGR pregnancies (birth weight <10th percentile for gestational age
      [GA]) delivered in our unit over 6 years. Cases were compared with controls for
      the association between abnormal MMS and adverse perinatal outcomes (APO).
      RESULTS: Of the 261 IUGR pregnancies, 39 (16%) had at least 1 APO. An elevated
      HCG was significantly associated with an APO (OR 2.6, 95% CI 1.1-6.4). A low uE3
      was also associated with an APO (OR 5.5, 95% CI 2.2-14). The association between
      an elevated AFP and APO was not statistically significant (OR 1.6, 95% CI, 0.6
      4.6). CONCLUSION: An elevated HCG and low uE3 were associated with APO in cases
      of IUGR. This information could be useful in identifying a subset of IUGR cases
      deserving closer surveillance.

PMID- 15507985
TI  - Enhanced growth and improved vascular function in offspring from successive
      pregnancies in endothelial nitric oxide synthase knockout mice.
AB  - OBJECTIVE: Transgenic mice that lack endothelial nitric oxide synthase have
      offspring with growth deficiency and abnormal vascular reactivity in later life.
      Our objective was to evaluate the role of parity in the modulation of the fetal
      programming of growth and vascular responses in these transgenic mice. STUDY
      DESIGN: Oligoparous (0-2 previous pregnancies) and multiparous (5-9 previous
      pregnancies) nitric oxide synthase knockout (-/-KO) female mice were bred with
      nitric oxide synthase -/-KO and wild type (+/+WT) male mice to produce nitric
      oxide synthase -/-KO and maternally derived heterozygous (+/-Mat) litters. The
      pups were weighed weekly. Carotid arteries of the adult females from these
      litters were used for in vitro vascular reactivity studies. RESULTS: Nitric oxide
      synthase knockout and nitric oxide synthase maternal litters that were born to
      oligoparous mothers had significant growth lag compared with corresponding
      multiparous litters. Length-tension characteristics were not different between
      the groups. However, optimal diameter, which is a measure of vascular tensile
      properties and resistance, was decreased in oligoparous compared with multiparous
      female offspring. Acetylcholine-mediated vasorelaxation was abolished, and
      contraction by phenylephrine and Ca ++ was increased in oligoparous, but not
      multiparous, female offspring ( P < .05). CONCLUSION: These data support the role
      of abnormal uterine environment in the fetal programming of postnatal growth and
      vascular function in later life. Successive pregnancies may lead to maternal
      uterine adaptations that bypass the lack of a functional nitric oxide synthase,
      which leads to improvement in postnatal growth and vascular function in the
      offspring. Given the reported effect of parity on the risk of preeclampsia,
      similar mechanisms may be operative in human pregnancy.

PMID- 15507986
TI  - What antepartum fetal test should guide the timing of delivery of the preterm
      growth-restricted fetus? A decision-analysis.
AB  - OBJECTIVE: The purpose of this study was to use a decision-analytic approach to
      explore the best strategy for the timing of the delivery of preterm intrauterine
      growth-restricted fetuses. STUDY DESIGN: We constructed a decision-analysis model
      that compared 4 antenatal fetal testing strategies The fetal/neonatal states that
      were compared included live in utero pregnancy; fetal death; neonatal death;
      disabled neonate, and healthy neonate. Probability estimates for these states and
      sensitivity and specificity for Doppler velocimetry and biophysical profile were
      derived from literature review. Sensitivity analyses were performed on the
      baseline assumptions. RESULTS: Under the baseline assumptions, biophysical
      profile was the best test to guide decisions on delivery. Sensitivity analyses
      revealed the model to be sensitive only to the specificity of a biophysical
      profile <82%. CONCLUSION: Compared with the other options, biophysical profile
      was the best strategy to guide physicians on the timing of the delivery of the
      preterm growth-restricted fetus.

PMID- 15507987
TI  - Use of the mitral valve-tricuspid valve distance as a marker of fetal endocardial
      cushion defects.
AB  - OBJECTIVE: The purpose of this study was to compare the mitral valve-tricuspid
      valve distance in second-trimester fetuses with normal cardiac anatomy versus
      those fetuses with endocardial cushion defects. STUDY DESIGN: We identified
      fetuses between 16 and 24 weeks of gestation. The distance between the insertions
      of the medial leaflets of the mitral and tricuspid valves were obtained. Linear
      regression curves were generated. RESULTS: The mean mitral valve-tricuspid valve
      distance for 86 fetuses with normal cardiac anatomy was 2.02 mm, compared with
      0.37 mm in 13 fetuses with endocardial cushion defects ( P = .0001). Linear
      regression curve correlating mitral valve-tricuspid valve distance with
      gestational age showed a gradual slope (R 2 = 0.28; P < .0001). With a mitral
      valve-tricuspid valve distance < 5th percentile as a marker for the diagnosis of
      endocardial cushion defect gave a sensitivity of 69.2%, a specificity of 100%, a
      positive predictive value of 100%, a negative predictive value of 95.6%, and a
      false-positive rate of 0% ( P = .0001). CONCLUSION: The mitral valve-tricuspid
      valve distance is useful clinically in the detection of endocardial cushion
      defects in second-trimester fetuses.

PMID- 15507988
TI  - Fetal cardiac defects and increased nuchal translucency thickness: a prospective
      study.
AB  - OBJECTIVE: The purpose of this study was to examine prospectively the association
      between increased nuchal translucency thickness and major cardiac defects in
      chromosomally normal fetuses. STUDY DESIGN: A prospective cohort study of 263
      chromosomally normal fetuses with an increased nuchal translucency thickness at
      11 to 14 weeks of gestation at a tertiary referral center was performed. The
      incidence of major cardiac defects was examined in relation to the fetal nuchal
      translucency thickness at the 11 to 14 week ultrasound examination. RESULTS: The
      nuchal translucency thickness measurements ranged from 2.2 to 8.0 mm (median, 3.1
      mm). There were 13 cases of major cardiac defects in this cohort, which gave a
      prevalence of 49.4 of every 1000 fetuses. With the use of the 99th percentile of
      nuchal translucency thickness, the prevalence rose to 106.7 of every 1000
      fetuses. CONCLUSION: In this population of chromosomally normal fetuses with an
      increased nuchal translucency thickness, the incidence of cardiac defects was
      high, which suggests that fetal echocardiography is indicated in this group.

PMID- 15507989
TI  - Defining standards of care in maternal-fetal medicine.
AB  - OBJECTIVE: The purpose of this study was to describe current practice patterns
      for 7 controversial topics in Maternal-Fetal Medicine. STUDY DESIGN: An
      interactive survey of obstetric treatment was performed as part of a postgraduate
      course at the 2004 Annual Meeting of the Society for Maternal-Fetal Medicine.
      Seven controversial topics were addressed, which included tocolytic therapy,
      progesterone supplementation for the prevention of preterm birth, screening for
      inherited thrombophilia, cervical cerclage for a shortened cervix, treatment of
      preterm premature rupture of membranes, magnesium sulfate seizure prophylaxis,
      and dexamethasone therapy for HELLP (hemolysis, elevated liver enzymes, and low
      platelet count) syndrome. RESULTS: A total of 298 obstetric care providers
      attended the postgraduate course. By report, most attendees were maternal-fetal
      medicine specialists (60.7% of respondents) who were >10 years out from specialty
      training (56.3% of respondents) and who were practicing in a university-based
      setting (52.9% of respondents). An average of 233 practitioners (range, 157-298
      practitioners) answered each question. An analysis of the responses allowed for
      the determination of current practice patterns in the 7 controversial areas
      addressed. CONCLUSION: Contemporary practice patterns for 7 controversial topics
      in obstetric medicine are described. Such surveys may be useful in defining
      standards of care in maternal-fetal medicine.

PMID- 15507990
TI  - Contemporary management of preterm premature rupture of membranes (PPROM): a
      survey of maternal-fetal medicine providers.
AB  - OBJECTIVE: This study was undertaken to characterize variations in the management
      for women with preterm premature rupture of membranes (PPROM) among maternal
      fetal medicine (MFM) specialists in the context of current recommendations for
      clinical practice and evidenced-based practice. STUDY DESIGN: We performed a Web
      based survey of 1375 MFM providers. Participants were queried on practice
      characteristics and management issues including use of tocolytics, antibiotics,
      steroids, and timing of delivery. RESULTS: A total of 508 providers (37%),
      representing all 50 states and 13 countries, responded to the survey. Only 30%
      reported a formal departmental protocol for managing women with PPROM. Consistent
      use of steroids (99.4%) and antibiotics (99.6%) were reported. Administration of
      steroids was confined to < or =32 weeks by 37%, and < or =34 weeks by 51% of
      practitioners. Repeated dosing of steroids was uncommon (16%). The antibiotics
      use and rationale for use varied among respondents. Tocolytics were used by 73%
      of respondents with magnesium sulfate the main agent used (98%). Use of
      tocolytics was generally used for 48 hours or less to attain steroid benefit
      (88%). Amniocentesis was used by 66% of practitioners in the acute evaluation of
      PPROM. Fetal lung maturity testing was reported by 78% with variability noted
      with respect to the test used. Outpatient management of women with PPROM after
      viability was noted by 43% of respondents. Gestational age at which expectant
      management is abandoned in women with PPROM varied significantly between
      respondents: > or =34 weeks by 56%, > pr =35 weeks by 26%, > or =36 weeks by 12%,
      and > or =37 weeks by 4.0%. CONCLUSION: Although many management practices for
      women with PPROM are consistent with currently available evidence and practice
      recommendations, substantial variations still exist among MFM providers.

PMID- 15507992
TI  - The uterine 1-layer closure.

PMID- 15507993
TI  - First-trimester prediction of growth discordance in dichorionic twin gestations.

PMID- 15507994
TI  - Experience with combined surgical treatment in cases of prolapse of pelvic
      organs.

PMID- 15507997
TI  - What we do and don't know about 'race', 'ethnicity', genetics and health at the
      dawn of the genome era.
AB  - A true understanding of disease risk requires a thorough examination of root
      causes. 'Race' and 'ethnicity' are poorly defined terms that serve as flawed
      surrogates for multiple environmental and genetic factors in disease causation,
      including ancestral geographic origins, socioeconomic status, education and
      access to health care. Research must move beyond these weak and imperfect proxy
      relationships to define the more proximate factors that influence health.

PMID- 15507996
TI  - Pregnancy-associated mortality after birth.

PMID- 15507998
TI  - Conceptualizing human variation.
AB  - What is the relationship between the patterns of biological and sociocultural
      variation in extant humans? Is this relationship accurately described, or best
      explained, by the term 'race' and the schema of 'racial' classification? What is
      the relationship between 'race', genetics and the demographic groups of society?
      Can extant humans be categorized into units that can scientifically be called
      'races'? These questions underlie the discussions that address the explanations
      for the observed differences in many domains between named demographic groups
      across societies. These domains include disease incidence and prevalence and
      other variables studied by biologists and social scientists. Here, we offer a
      perspective on understanding human variation by exploring the meaning and use of
      the term 'race' and its relationship to a range of data. The quest is for a more
      useful approach with which to understand human biological variation, one that may
      provide better research designs and inform public policy.

PMID- 15507999
TI  - Implications of biogeography of human populations for 'race' and medicine.
AB  - In this review, we focus on the biogeographical distribution of genetic variation
      and address whether or not populations cluster according to the popular concept
      of 'race'. We show that racial classifications are inadequate descriptors of the
      distribution of genetic variation in our species. Although populations do cluster
      by broad geographic regions, which generally correspond to socially recognized
      races, the distribution of genetic variation is quasicontinuous in clinal
      patterns related to geography. The broad global pattern reflects the accumulation
      of genetic drift associated with a recent African origin of modern humans,
      followed by expansion out of Africa and across the rest of the globe. Because
      disease genes may be geographically restricted due to mutation, genetic drift,
      migration and natural selection, knowledge of individual ancestry will be
      important for biomedical studies. Identifiers based on race will often be
      insufficient.

PMID- 15508000
TI  - Genetic variation, classification and 'race'.
AB  - New genetic data has enabled scientists to re-examine the relationship between
      human genetic variation and 'race'. We review the results of genetic analyses
      that show that human genetic variation is geographically structured, in accord
      with historical patterns of gene flow and genetic drift. Analysis of many loci
      now yields reasonably accurate estimates of genetic similarity among individuals,
      rather than populations. Clustering of individuals is correlated with geographic
      origin or ancestry. These clusters are also correlated with some traditional
      concepts of race, but the correlations are imperfect because genetic variation
      tends to be distributed in a continuous, overlapping fashion among populations.
      Therefore, ancestry, or even race, may in some cases prove useful in the
      biomedical setting, but direct assessment of disease-related genetic variation
      will ultimately yield more accurate and beneficial information.

PMID- 15508001
TI  - Will tomorrow's medicines work for everyone?
AB  - Throughout much of the world, 'race' and 'ethnicity' are key determinants of
      health. For example, African Americans have, by some estimates, a twofold higher
      incidence of fatal heart attacks and a 10% higher incidence of cancer than
      European Americans, and South Asian- or Caribbean-born British are approximately
      3.5 times as likely to die as a direct result of diabetes than are British of
      European ancestry. The health care that people receive also depends on 'race' and
      'ethnicity'. African Americans are less likely to receive cancer-screening
      services and more likely to have late-stage cancer when diagnosed than European
      Americans. Health disparities such as these are one of the greatest social
      injustices in the developed world and one of the most important scientific and
      political challenges.

PMID- 15508002
TI  - Are medical and nonmedical uses of large-scale genomic markers conflating
      genetics and 'race'?

PMID- 15508003
TI  - Assessing genetic contributions to phenotypic differences among 'racial' and
      'ethnic' groups.
AB  - Descriptions of human genetic variation given thirty years ago have held up well,
      considering the substantial accrual of DNA sequence data in the interim. Most
      importantly, estimates of between-group genetic variation have remained
      relatively low. Despite the low average level of between-group variation,
      clusters recently inferred from multilocus genetic data coincide closely with
      groups defined by self-identified race or continental ancestry. This
      correspondence implies that genetic factors might contribute to unexplained
      between-group phenotypic variation. Current understanding of the contribution of
      genes to variation in most complex traits is limited, however. Under these
      circumstances, assumptions about genetic contributions to group differences are
      unfounded. In the absence of detailed understanding, 'racial' and 'ethnic'
      categories will remain useful in biomedical research. Further, we suggest
      approaches and guidelines for assessing the contribution of genetic factors to
      between-group phenotypic differences, including studies of candidate genes and
      analyses of recently admixed populations.

PMID- 15508004
TI  - Changing the paradigm from 'race' to human genome variation.
AB  - Knowledge from the Human Genome Project and research on human genome variation
      increasingly challenges the applicability of the term 'race' to human population
      groups, raising questions about the validity of inferences made about 'race' in
      the biomedical and scientific literature. Despite the acknowledged contradictions
      in contemporary science, population-based genetic variation is continually used
      to explain differences in health between 'racial' and 'ethnic' groups. In this
      commentary we posit that resolution of apparent paradoxes in relating biology to
      'race' and genetics requires thinking 'outside of the box'.

PMID- 15508005
TI  - Implications of correlations between skin color and genetic ancestry for
      biomedical research.
AB  - Skin pigmentation is a central element of most discussions on 'race' and
      genetics. Research on the genetic basis of population variation in this
      phenotype, which is important in mediating both social experiences and
      environmental exposures, is sparse. We studied the relationship between
      pigmentation and ancestry in five populations of mixed ancestry with a wide range
      of pigmentation and ancestral proportions (African Americans from Washington, DC;
      African Caribbeans living in England; Puerto Ricans from New York; Mexicans from
      Guerrero; and Hispanics from San Luis Valley). The strength of the relationship
      between skin color and ancestry was quite variable, with the correlations ranging
      in intensity from moderately strong (Puerto Rico, rho = 0.633) to weak (Mexico,
      rho = 0.212). These results demonstrate the utility of ancestry-informative
      genetic markers and admixture methods and emphasize the need to be cautious when
      using pigmentation as a proxy of ancestry or when extrapolating the results from
      one admixed population to another.

PMID- 15508007
TI  - Sanctions on scientific publication.

PMID- 15508009
TI  - Emotional vision.

PMID- 15508010
TI  - Nucleokinesis illuminated.

PMID- 15508011
TI  - Messing about in memory.

PMID- 15508012
TI  - Decision making, performance and outcome monitoring in frontal cortical areas.

PMID- 15508013
TI  - Festina lente: late-night thoughts on high-throughput screening of mouse
      behavior.
AB  - A recent perspective discussed high-throughput behavioral analysis using mice,
      giving the overall impression that this area is lagging behind in neuroscience
      and biomedical research. Not only are we more optimistic about the current state
      of the art in behavioral neuroscience and its promise, but we also have
      reservations about whether high-throughput analysis is always an appropriate goal
      for most behavioral studies. We argue that behavioral studies should be carried
      out with clear goals and more regard to the intellectual context in which they
      have developed. In addition, behavioral studies can be performed quite easily,
      but this does not ensure the required validity or reliability of the particular
      tests used. Finally, high throughput may not always be an appropriate goal. We
      discuss the role of automated data collection and unique data-mining algorithms,
      and the question of the ethological relevance of behavioral tests.

PMID- 15508014
TI  - Lupin kernel fibre-enriched foods beneficially modify serum lipids in men.
AB  - OBJECTIVE: To examine the effect of a diet containing a novel legume food
      ingredient, Australian sweet lupin (Lupinus angustifolius) kernel fibre
      (LKFibre), compared to a control diet without the addition of LKFibre, on serum
      lipids in men. DESIGN: Randomized crossover dietary intervention study. SETTING:
      Melbourne, Australia--Free-living men. SUBJECTS: A total of 38 healthy males
      between the ages of 24 and 64 y completed the intervention. INTERVENTION:
      Subjects consumed an LKFibre and a control diet for 1 month each. Both diets had
      the same background menus with seven additional experimental foods that either
      contained LKFibre or did not. Depending on energy intake, the LKFibre diet was
      designed to contain an additional 17 to 30 g/day fibre beyond that of the control
      diet. RESULTS: Compared to the control diet, the LKFibre diet reduced total
      cholesterol (TC) (mean+/-s.e.m.; 4.5+/-1.7%; P=0.001), low-density lipoprotein
      cholesterol (LDL-C) (5.4+/-2.2%; P=0.001), TC: high-density lipoprotein
      cholesterol (HDL-C) (3.0+/-2.0%; P=0.006) and LDL-C:HDL-C (3.8+/-2.6%; P=0.003).
      No effects on HDL-C, triacylglycerols, glucose or insulin were observed.
      CONCLUSIONS: Addition of LKFibre to the diet provided favourable changes to some
      serum lipid measures in men, which, combined with its high palatability, suggest
      this novel ingredient may be useful in the dietary reduction of coronary heart
      disease risk.

PMID- 15508015
TI  - Safety and intestinal tolerance of high-dose enteral antioxidants and glutamine
      peptides after upper gastrointestinal surgery.
AB  - OBJECTIVE: Safety and intestinal tolerance of an early high-dose enteral
      administration of antioxidative vitamins, trace elements, and glutamine
      dipeptides. DESIGN: open intervention trial. SETTING: Two university teaching
      hospitals. PATIENTS: A total of 14 patients requiring jejunal feeding (64+/-14
      y). INTERVENTION: A measure of 500 ml/day Intestamin (FreseniusKabi: 250
      kcal/1.050 kJ, 300 microg selenium, 20 mg zinc, 400 mug chromium, 1500 mg vitamin
      C, 500 mg vitamin E, 10 mg beta-carotene, 30 g glutamine) for 5 days beginning 6
      h after surgery. Parenteral/enteral nutrition was provided to achieve energy
      target (25 kcal/kg/day). ASSESSMENTS: Intestinal complaints, plasma nutrients,
      and glutathione. RESULTS: Only minor signs of nausea, hiccups, flatulence (3/14).
      Plasma micronutrients (except beta-carotene) postoperatively decreased and
      increased to normal on day 5. Extracellular glutamine remained low (preop: 520+/
      94; d1: 357+/-67; d5: 389+/-79 micromol/l); total glutathione decreased (d1:
      9.4+/-3.8; d5: 3.6+/-2.5 micromol/l). CONCLUSION: Study feed is well tolerated
      and metabolically safe representing a valuable tool for targeted pharmaconutrient
      supply.

PMID- 15508016
TI  - Low plasma vitamin E levels in major depression: diet or disease?
AB  - OBJECTIVE: Levels of vitamin E have been reported to be lower in patients
      suffering major depression, but whether this is due to inadequate dietary intake
      or the pathophysiology of depression is not known, and was the subject of the
      present study. SETTING: Wollongong, Australia. METHODS: Plasma vitamin E (alpha
      tocopherol) was measured in 49 adults with major depression, age (mean+/-s.d.):
      47+/-12 y. In a subset (n=19) usual dietary intake of vitamin E was determined by
      diet history. RESULTS: Subjects had significantly lower plasma alpha-tocopherol
      (4.71+/-0.13 mumol/mmol cholesterol) than has previously been reported for
      healthy Australians, and plasma alpha-tocopherol was inversely related to
      depression score (by Beck Depression Inventory) (r=-0.367, P<0.009). Diet
      analysis indicated that 89% of subjects met or exceeded the recommended intake
      for vitamin E, and dietary intake was not related to plasma alpha-tocopherol
      level in this subset. CONCLUSION: These findings suggest that plasma levels of
      alpha-tocopherol are lower in depression, but this is not likely to be the result
      of inability to meet recommended dietary intake. .

PMID- 15508017
TI  - Supernumerary marker chromosomes in man: parental origin, mosaicism and maternal
      age revisited.
AB  - The details of all cytogenetic abnormalities diagnosed in the Wessex Regional
      Genetics Laboratory (WRGL) since 1967 to the present day have been recorded in
      the Salisbury Treasury of Interesting Chromosomes (STOIC). From this resource, we
      identified 137 patients with constitutional autosomal supernumerary marker
      chromosomes (SMC) ascertained in four principal groups: (i) 37% with abnormal
      phenotypes; (ii) 7% couples with reproductive difficulties; (iii) 47% antenatal
      diagnoses and (iv) 9% miscellaneous. Overall, 81 (59%) SMCs were mosaics and 56
      (41%) nonmosaics. Of the 109 cases with known parental origins, 70% were de novo,
      19% maternally and 11% paternally inherited. The chromosomal origins of 112/137
      (82%) of the SMCs have been determined by fluorescence in situ hybridization
      (FISH). In all, 36/112 (32%) were derived from nonacrocentric autosomes, and
      76/112 (68%) from the acrocentric autosomes 13/21, 14, 15 and 22. Of these
      acrocentric SMCs, 39 (51%) were derived from chromosome 15, so that SMC(15)
      constituted 39/112 (35%) of all SMCs with known chromosomal origins. The
      frequencies with which mosaicism was observed varied considerably according to
      the chromosomal origin of the SMCs and accounted for 8/39 (20%) SMC(15), 13/37
      (35%) SMCs from other acrocentrics and 25/36 (69%) of nonacrocentric SMCs. The
      data were analysed for parental age effects, and only de novo SMC(15)s were found
      to be associated with a significantly increased maternal age.

PMID- 15508018
TI  - Mutation in the 5' alternatively spliced region of the XNP/ATR-X gene causes
      Chudley-Lowry syndrome.
AB  - The Chudley-Lowry syndrome (ChLS, MIM 309490) is an X-linked recessive condition
      characterized by moderate to severe mental retardation, short stature, mild
      obesity, hypogonadism, and distinctive facial features characterized by depressed
      nasal bridge, anteverted nares, inverted-V-shaped upper lip, and macrostomia. The
      original Chudley-Lowry family consists of three affected males in two
      generations. Linkage analysis had localized the gene to a large interval, Xp21
      Xq26 and an obligate carrier was demonstrated to have highly skewed X
      inactivation. The combination of the clinical phenotype, consistent with that of
      the patients with ATR-X syndrome, the skewed X-inactivation pattern in a carrier
      female, as well as the mapping interval including band Xq13.3, prompted us to
      consider the XNP/ATR-X gene being involved in this syndrome. Using RT-PCR
      analysis, we screened the entire XNP/ATR-X gene and found a mutation in exon 2
      (c.109C > T) giving rise to a stop codon at position 37 (p.R37X). Western blot
      and immunocytochemical analyses using a specific monoclonal antibody directed
      against XNP/ATR-X showed the protein to be present in lymphoblastoid cells from
      one affected male, despite the premature stop codon. To explain these discordant
      results, we further analyzed the 5' region of the XNP/ATR-X gene and found three
      alternative transcripts, which differ in the presence or absence of exon 2, and
      the length of exon 1. Our data suggest that ChLS is allelic to the ATR-X syndrome
      with its less severe phenotype being due to the presence of some XNP/ATR-X
      protein.

PMID- 15508019
TI  - Computer dating for proteins.

PMID- 15508020
TI  - Effect of short-term cigarette smoke exposure on body weight, appetite and brain
      neuropeptide Y in mice.
AB  - Although nicotinic receptors have been demonstrated in hypothalamic appetite
      regulating areas and nicotine administration alters food intake and body weight
      in both animals and humans, the mechanisms underlying the effects of smoking on
      appetite circuits remain unclear. Conflicting effects of nicotine on the major
      orexigenic peptide, neuropeptide Y (NPY), have been observed in the brain, but
      the effects of smoking are unknown. Thus, we aimed to investigate how cigarette
      smoking affects body weight, food intake, plasma leptin concentration,
      hypothalamic NPY peptide, adipose mass and mRNA expression of uncoupling proteins
      (UCP), and tumor necrosis factor (TNF) alpha. Balb/C mice (8 weeks) were exposed
      to cigarette smoke (three cigarettes, three times a day for 4 consecutive days)
      or sham exposed. Body weight and food intake were recorded. Plasma leptin and
      brain NPY were measured by radioimmunoassay. UCPs and TNF alpha mRNA were
      measured by real-time PCR. Food intake dropped significantly from the first day
      of smoking, and weight loss became evident within 2 days. Brown fat and
      retroperitoneal white fat masses were significantly reduced, and plasma leptin
      concentration was decreased by 34%, in line with the decreased fat mass. NPY
      concentrations in hypothalamic subregions were similar between two groups. UCP1
      mRNA was decreased in white fat and UCP3 mRNA increased in brown fat in smoking
      group. Short-term cigarette smoke exposure led to reduced body weight, food
      intake, and fat mass. The reduction in plasma leptin concentration may have been
      too modest to increase NPY production; alternatively, change in NPY or its
      function might have been offset by nicotine or other elements in cigarette smoke.

PMID- 15508021
TI  - Mu-opioid self-administration vs passive administration in heroin abusers
      produces differential EEG activation.
AB  - Psychoactive drug self-administration (SA) produces different neurobiological
      effects than passive administration (PA) in non-human animals; however, such
      consequences have never been examined in human drug abusers. The present study
      compared electroencephalographic (EEG) activation produced by intravenous PA and
      SA of the mu-opioid fentanyl in eight heroin-dependent, methadone-stabilized male
      participants. In phase 1, participants received cumulative PA of fentanyl (up to
      1.5 mg/70 kg; session 1), then bolus PA of placebo and fentanyl 1.5 mg/70 kg
      (session 2). High-dose fentanyl significantly increased the amplitude of slow
      frequency (delta- and theta-band) EEG activity. In phase 2, bolus fentanyl 1.5
      mg/70 kg was available for SA, requiring the participant to complete 1500
      responses, in each of two sessions after saline or naloxone pretreatment. Delta
      EEG peak amplitude increases were greater following fentanyl SA than fentanyl PA,
      primarily over the central midline region, and were attenuated by naloxone
      pretreatment. The EEG increase and its attenuation by naloxone agree with
      preclinical evidence and suggest that SA-related EEG responses were mediated by
      opioid receptors.

PMID- 15508022
TI  - Neonatal isolation stress potentiates cocaine seeking behavior in adult male and
      female rats.
AB  - Little is known with regard to how sex and stress might interact as vulnerability
      factors in cocaine abuse. In this study, we compared the effects of neonatal
      isolation stress on cocaine self-administration under extended access conditions
      and on subsequent responding in a cue-induced reinstatement paradigm in adult
      male and female rats. Pups from each litter were subjected to either neonatal
      isolation (1 h/day) or brief daily handling from postnatal day 2 through 12.
      Adults rats were then trained to self-administer cocaine, and once they acquired
      lever responding for cocaine under a fixed ratio 1 schedule, they were given 24-h
      access to intravenous cocaine infusions (1.5 mg/kg) that were available in
      discrete trials (4, 10 min trials/h) for 7 consecutive days. At 10 days after the
      last discrete trial session, responding was assessed during six to eight 1-h
      extinction sessions that were followed by a 1-h cue-induced reinstatement
      session. Results revealed that females took more cocaine than did males over the
      7-day discrete trial self-administration period and tended to respond at higher
      levels during the initial extinction sessions. Although intake did not differ
      between handled control rats and isolated rats under extended access conditions,
      stress effects were observed under subsequent extinction and cue-induced
      reinstatement testing conditions with isolated rats responding at higher levels
      during both phases. Notably, stress seemed to obscure sex differences in
      extinction responding such both isolated males and females responded at high
      levels. These findings demonstrate robust and enduring effects of neonatal
      isolation stress on cocaine seeking behavior in adult male and female rats.

PMID- 15508023
TI  - Confirmation of a major QTL influencing oral morphine intake in C57 and DBA mice
      using reciprocal congenic strains.
AB  - C57BL/6 (B6) and DBA/2 (D2) mice exhibit disparate behavior when tested for
      voluntary morphine intake in a two-bottle choice drinking paradigm with B6 mice
      consuming 10 times more drug than D2 mice. Previous genetic mapping studies
      identified a locus, Mop2, on the proximal part of chromosome 10 that explained
      over half of the genetic variance in this mouse model of opioid self
      administration. We constructed a set of reciprocal congenic strains between B6
      and D2 mice in which the proximal portion of chromosome 10 has been introgressed
      from one strain onto the background of the other. We tested mice from this pair
      of reciprocal strains together with progenitor B6 and D2 mice in a two-bottle
      choice drinking paradigm with morphine and quinine. The results showed that
      introgression of chromosome 10 alleles from the B6 strain onto a D2 genetic
      background increased voluntary morphine intake four-fold compared to progenitor
      D2 mice. Preference for morphine was also increased significantly in D2.B6-Mop2
      mice compared to progenitor D2 mice. Conversely, introgression of chromosome 10
      alleles from the D2 strain onto a B6 genetic background decreased morphine intake
      by half compared to progenitor B6 mice in B6.D2 -Mop2 mice; however, high
      morphine preference was maintained in this congenic strain most likely due to
      strong quinine aversion. When quinine was eliminated from the control bottle,
      morphine preference in B6.D2-Mop2 mice was decreased significantly relative to B6
      and D2.B6-Mop2 mice. Overall, these data confirm the existence of a gene(s) on
      chromosome 10 proximal to D10Mit124 that has a strong influence on the difference
      in morphine drinking behavior between B6 and D2 mice.

PMID- 15508024
TI  - Cognitive sequelae of intravenous amphetamine self-administration in rats:
      evidence for selective effects on attentional performance.
AB  - Characterizing the nature and severity of cognitive deficits associated with
      chronic stimulant abuse may provide new insights into the neural substrates of
      drug addiction because such deficits may contribute to the chronic relapsing
      nature of compulsive drug use. This investigation examines in rats the long-term
      cognitive consequences of intravenously self-administered amphetamine,
      specifically on performance of a 5-choice serial reaction time task (5-CSRTT),
      which assesses visuo-spatial attention and impulsivity. Rats experienced 5 days
      of intravenous (i.v.) amphetamine self-administration and were then withdrawn for
      a period of 9 days, during which time testing on the 5-CSRTT took place. This was
      repeated on five consecutive occasions for a period of 10 weeks. Controls
      experienced identical training on the 5-CSRTT but during the self-administration
      sessions received yoked i.v. infusions of normal saline. The results reveal a
      selective and reproducible pattern of deficits on the 5-CSRTT following repeated
      withdrawal from amphetamine self-administration, with deleterious effects on the
      speed and accuracy of responding as well as increased omission errors. Premature
      (impulsive) responding, perseveration, and food consumption latencies were not
      significantly affected. Deficits in attentional performance fully recovered 4-5
      days after amphetamine cessation and there was no evidence of any long-term
      disturbances, even when the attentional load was increased. However, following a
      2-month abstinence period, abnormalities in the subsequent effects of acute
      noncontingent amphetamine were found, with increased omissions, slower response
      times, and reduced impulsivity. Thus, contingent i.v. amphetamine administration
      has both short- and long-term consequences, which may be relevant to the complex
      disturbances that accompany drug addiction.

PMID- 15508026
TI  - Amperometric determination of nitric oxide derived from pulmonary artery
      endothelial cells immobilized in a microchip channel.
AB  - A simple method for immobilizing a confluent layer of bovine pulmonary artery
      endothelial cells (bPAECs) in microchip-based channels is described. The
      microchips are prepared from poly(dimethylsiloxane) and have channel dimensions
      that approximate resistance vessels in vivo. The reversibly sealed channels were
      coated with fibronectin (100 microg ml(-1)) by aspiration. The bPAECs, which were
      introduced in the same manner, became attached to the fibronectin coating in
      about 2 h. The microchip could then be resealed over a micromolded carbon ink
      electrode (24 microm width x 6 microm height). Coating the carbon microelectrode
      with a 0.05% Nafion solution selectively blocked nitrite (10 microM) from being
      transported to the electrode surface while nitric oxide (NO, 10 microM) was
      amperometrically measured. Upon stimulation with adenosine triphosphate (ATP, 100
      microM) the immobilized bPAECs produced and released micromolar amounts of NO.
      This NO production was effectively inhibited when the immobilized cells were
      incubated with L-nitro-arginine methyl ester (L-NAME), a competitive inhibitor
      for nitric oxide synthase. Moreover, once the immobilized bPAECs were no longer
      able to produce NO, incubation with L-arginine allowed for further ATP-stimulated
      NO production.

PMID- 15508029
TI  - Examination of bilayer lipid membranes for 'pin-hole' character.
AB  - BLM prepared on electrode substrates by supporting or tethering were tested for
      'pin-hole' character, comparing data from cyclic voltammetry (CV), surface
      plasmon resonance (SPR) and rotating disc electrodes (RDE). 1-hexadecylamine
      tethered BLMs on SAM modified gold electrodes were compared with BLMs assembled
      on modified polyHEMA or sol-gel layers. BLM formation followed by SPR showed that
      the initial phase of the assembly was complete in 5-20 minutes and produced
      layers of thickness >5 nm, compared with the expected final BLM thickness of
      approximately 3 nm. The CVs of the K(3)[Fe(CN)(6)] couple were significantly
      suppressed irrespective of the method of BLM assembly, without major differences
      emerging for the different methods. However, data from the RDE distinguished the
      'pin-hole' character of the different preparations. The data were consistent with
      incomplete initial (<1 h, SPR estimated BLM thickness >5 nm) vesicle fusion
      leaving 'pin-holes' of approximately 2 microm (HDA-11-mercaptoundecanoic acid
      (MUA) tethered BLM) to approximately 3 microm (tetraethylorthosilicate sol-gel
      supported BLM) followed by a slow maturation (>15 h; impedance spectroscopy
      estimated thickness approximately 3 nm) and lateral spreading and fusion,
      resulting in loss of 'pin-hole' character (<1 microm). The BLM could be used in
      conjunction with potentiometric measurement to observe the incorporation of
      nystatin into the BLM and the rate of incorporation adjusted according to
      original permeability of the BLM. The 'pin-hole-free' BLM construction with
      lowest permeability (TEOS supported, 4 x 10(-10) cm s(-1) compared with HDA-MUA,
      3 x 10(-9) cm s(-1)) gave a potentiometric signal independent of bulk ion
      concentration across 5 decades change in concentration. Formed on an ion
      selective electrode, nystatin incorporation could be followed as a change in
      potential, over >2 h, whereas the TEOS supported BLM with permeability 1 x 10(-9)
      cm s(-1) shows nystatin incorporation within 1 h. In this instance, addition of
      ConA reduced the potential to the same value as prior to nystatin incorporation,
      consistent with nystatin channel closure.

PMID- 15508031
TI  - Rapid, quantitative analysis of ppm/ppb nicotine using surface-enhanced Raman
      scattering from polymer-encapsulated Ag nanoparticles (gel-colls).
AB  - Rapid, quantitative SERS analysis of nicotine at ppm/ppb levels has been carried
      out using stable and inexpensive polymer-encapsulated Ag nanoparticles (gel
      colls). The strongest nicotine band (1030 cm(-1)) was measured against d(5)
      pyridine internal standard (974 cm(-1)) which was introduced during preparation
      of the stock gel-colls. Calibration plots of I(nic)/I(pyr) against the
      concentration of nicotine were non-linear but plotting I(nic)/I(pyr) against
      [nicotine](x)(x = 0.6-0.75, depending on the exact experimental conditions) gave
      linear calibrations over the range (0.1-10 ppm) with R(2) typically ca. 0.998.
      The RMS prediction error was found to be 0.10 ppm when the gel-colls were used
      for quantitative determination of unknown nicotine samples in 1-5 ppm level. The
      main advantages of the method are that the gel-colls constitute a highly stable
      and reproducible SERS medium that allows high throughput (50 sample h(-1))
      measurements.

PMID- 15508030
TI  - Arrays of horizontally-oriented mini-reservoirs generate steady microfluidic
      flows for continuous perfusion cell culture and gradient generation.
AB  - This paper describes the use of arrays of horizontally-oriented reservoirs to
      deliver liquids through microchannels at a constant flow rate over extended
      periods of time (hours to days). The horizontal orientation maintains a constant
      hydraulic pressure drop across microfluidic channels even as the volumes of
      liquids within the reservoirs change over time. For a given channel-reservoir
      system, the magnitude of the flow velocity depends linearly on the height
      difference between reservoirs. The simple structure and operation mechanism make
      this pumping system versatile. A one-inlet-one-outlet system was used to
      continuously deliver media for perfusion cell culture, and an array of inlet
      reservoirs coupled to an outlet reservoir via microchannels was used to drive
      flows of multiple laminar streams. The parallel pumping scheme conveniently
      generated various smooth and step concentration gradients, and allowed evaluation
      of the effect of colchicine on myoblasts. Since the reservoir arrays are
      configured to be compatible with commercialized multichannel pipettors designed
      for 96 well plate handling, this simple pumping scheme is envisioned to be
      broadly useful for medium to high throughput microfluidic perfusion cell culture
      assays, cell migration assays, multiple laminar flow drug tests, and any other
      applications needing multiple microfluidic streams.

PMID- 15508033
TI  - Analytical chemistry of synthetic routes to psychoactive tryptamines. Part I.
      Characterisation of the Speeter and Anthony synthetic route to 5-methoxy-N,N
      diisopropyltryptamine using ESI-MS-MS and ESI-TOF-MS.
AB  - 5-Methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT), a new psychoactive tryptamine
      derivative, has been synthesised by the Speeter and Anthony procedure. This
      synthetic route was characterised by ESI-MS-MS, ESI-TOF-MS and NMR. Side products
      have been identified as 3-(2-N,N-diisopropylamino-ethyl)-1H-indol-5-ol (5), 2-N,N
      diisopropylamino-1-(5-methoxy-1H-indol-3-yl)-ethanol (6), 2-(5-methoxy-1H-indol-3
      yl)-ethanol (7) and 2-N,N-diisopropylamino-1-(5-methoxy-1H-indol-3-yl)-ethanone
      (8).

PMID- 15508034
TI  - Arsinothioyl-sugars produced by in vitro incubation of seaweed extract with liver
      cytosol analysed by HPLC coupled simultaneously to ES-MS and ICP-MS.
AB  - It has been shown, that in vitro incubation of Laminaria digitata extract
      (containing mainly As-sugar 1 (glycerol-arsenoribose) and As-sugar 3 (sulfonate
      arsenoribose)) with liver cytosol, produced the same two arsenicals, as when L.
      digitata extract was treated with H(2)S. By parallel use of HPLC-ICP-MS and HPLC
      ES-MS the compounds displayed mainly m/z 345 and m/z 409. A pure As-sugar 1
      standard was obtained, and a standard of arsinothioyl-sugar 1 (m/z 345) was
      produced, by purging a solution of As-sugar 1 with gaseous H(2)S. The identity of
      arsinothioyl-sugar 1 was characterised by ES-MS, 1D and 2D NMR. Arsinothioyl
      sugar 1 showed the same chromatographic behaviour and MS characteristics as one
      of the two arsenic-containing compounds (m/z 345) produced by incubation of L.
      digitata extracts with liver cytosol, and as the product of the incubation of As
      sugar 1 with liver cytosol (HPLC-ICP-MS, HPLC-ES-MS). Assuming that As-sugar 3
      reacts in a similar way to As-sugar 1 with H(2)S, it is most likely that the
      second unknown (m/z 409) is arsinothioyl-sugar 3. The degradation of As-sugar 1
      in acidic solution (100 mM HCl) was followed by (1)H-NMR, and the relative slow
      degradation (t(1/2)= 17 h) suggests that arsenosugars are taken up from the
      stomach in their original chemical form, hence the study of arsenosugar
      incubation in tissue is highly relevant. The arsinothioyls are a new group of
      organoarsenicals, which have only recently been identified in nature. Here,
      arsinothioyl sugars are detected for the first time. The in vitro formation of
      arsinothioyl-sugars in liver cytosol suggests that arsinothioyls may be of large
      biochemical and toxicological importance.

PMID- 15508035
TI  - In-tube solid-phase microextraction with poly(methacrylic acid-ethylene glycol
      dimethacrylate) monolithic capillary for direct high-performance liquid
      chromatographic determination of ketamine in urine samples.
AB  - Ketamine was used for anaesthesia originally but has emerged as an abused drug in
      recent years. The prevalence of ketamine abuse demands a direct and rapid
      determination method. It is known that in-tube solid phase microextraction (in
      tube SPME) can perform extraction with a capillary linked directly to a HPLC
      system, providing an automated and accurate extraction procedure. In this paper,
      an in-tube SPME coupled to HPLC method was developed for the determination of
      ketamine in urine samples with a poly(methacrylic acid-ethylene glycol
      dimethacrylate) monolithic capillary column as the extraction phase, which is
      expected to provide higher extraction efficiency than open tubular capillaries.
      After optimizing the extraction conditions, ketamine was extracted directly from
      urine samples in a wide dynamic linear range of 50-10,000 ng mL(-1), with the
      detection limit obtained as 6.4 ng mL(-1). The intra-day and inter-day precision
      for the method was 1.6% and 1.7%, respectively. The urine samples from suspect
      addicts have been successfully analyzed within 20 min. The re-usability of the
      monolithic column was also confirmed as no decrease of the extraction efficiency
      was shown after urine extraction.

PMID- 15508037
TI  - Electrochemical detection of amino acids at carbon nanotube and nickel-carbon
      nanotube modified electrodes.
AB  - The oxidation and enhanced detection of traditionally 'non-electroactive' amino
      acids at a single-wall carbon nanotube (SWNT) surface and at a nickel hydroxide
      film electrochemically deposited and generated upon the SWNT layer is reported.
      Different CNT are compared, with Nafion-dispersed SWNT offering the most
      favorable layer for constant-potential amperometric detection. Factors affecting
      the oxidation process, including the pH or applied potential, are assessed. The
      response of the SWNT-Nafion coated electrode compares favorably with that of
      copper and nickel disk electrodes under flow injection analysis (FIA) conditions.
      The electrodeposition of nickel onto the SWNT-Nafion layer (Ni-CNT) led to a
      dramatic enhancement of the analytical response (vs. that observed at the SWNT or
      nickel electrodes alone). The oxidative process at the Ni(OH)(2) layer has been
      studied and the increase in sensitivity rationalized. In the presence of amino
      acid the Ni-CNT layer undergoes an electrocatalytic process in which the amino
      acid reduces the newly formed NiO(OH) species. Furthermore, the attractive
      response of both the CNT and Ni-CNT layers has allowed these electrodes to be
      used for constant-potential FIA of various amino acids and indicates great
      promise for monitoring chromatographic effluents. Once again an improved signal
      was observed at the Ni-CNT electrode compared to nickel deposited upon a bare
      glassy carbon electrode (Ni-GC).

PMID- 15508038
TI  - A study of Nafion-coated bismuth-film electrodes for the determination of trace
      metals by anodic stripping voltammetry.
AB  - This work reports on the fabrication, characterization and applications of Nafion
      coated bismuth-film electrodes (NCBFE's) for the determination of trace metals by
      anodic stripping voltammetry (ASV). A NCBFE was typically prepared by first
      applying a 5 microl drop of a 1% Nafion solution onto the surface of a glassy
      carbon rotating-disk electrode. After evaporation of the solvent, the Bi film was
      plated on the electrode in situ(i.e. by spiking the sample with 1000 microg l(-1)
      of Bi(iii) and simultaneous electrolytic deposition of the metal ions and bismuth
      film on the electrode surface at -1.4 V) or ex-situ(i.e. by electrolytic
      deposition of the bismuth film in a separate solution containing 1000 microg l(
      1) of Bi(iii), followed by the ASV measurement step in the sample solution).
      Various fabrication and operational parameters were thoroughly investigated and
      discussed in terms of their effect on the ASV signals. It was found that this
      voltammetric sensor was suitable for the determination of metals at trace levels
      by square-wave ASV (SWASV) due to its multi-element detection potential, improved
      analytical sensitivity, high resistance to surfactants, low cost, ease of
      fabrication, robustness, speed of analysis and low toxicity (as compared to
      traditional mercury electrodes). In the presence of 4 mg l(-1) of Triton X-100,
      the NCBFE afforded a 10-fold peak height enhancement for the Pb peak and a 14
      fold enhancement for the Cd peak over a bare BFE while the determination of Zn
      was feasible only on the NCBFE. The limits of detection (at a signal-to-noise
      ratio of 3) were 0.1 microg l(-1) for Cd and Pb and 0.4 microg l(-1) for Zn for a
      deposition time of 10 min. Finally, the electrode was applied to different real
      samples (tap-water, urine and wine) for the analysis of trace metals with
      satisfactory results.

PMID- 15508039
TI  - Strategy for streamlined release identity testing of chromatography media.
AB  - In accordance with the US Code of Federal Regulations 21CFR 211.84 (6)(d)(1), a
      specific identity test must be performed for the release of chromatography media
      (stationary phase) before use in production of human pharmaceuticals. Due to the
      complexity of the physical and chemical properties of these media, i.e., variable
      particle morphology, insolubility, and chemical inertness, the development of
      specific identity tests presents a challenge. In this paper we report a new
      strategy for media identification that uses a combination of three relatively
      simple techniques: Fourier transform infrared (FT-IR) and near infrared (NIR)
      spectroscopy in conjunction with search libraries, and particle size distribution
      analysis. The methods are well established and suitable for routine application
      in a quality control laboratory. A hierarchical selection procedure utilizing
      these methods permits assignment of a unique identity for each of the
      chromatography media in use at a given facility, and form the basis of release
      tests for the media. Although this strategy was developed using specific media,
      the generic nature of the technology and the selection strategy proposed would
      permit its application to other chromatography media as well.

PMID- 15508041
TI  - Identification of synthetic precursors of amphetamine-like drugs using Raman
      spectroscopy and ab initio calculations: beta-Methyl-beta-nitrostyrene
      derivatives.
AB  - The present work reports a vibrational spectroscopic study of several beta-methyl
      beta-nitrostyrene derivatives, which are important intermediates in the synthesis
      of illicit amphetamine-like drugs, such as 3,4-methylenedioxymethamphetamine
      (MDMA), 3,4-methylenedioxyamphetamine (MDA), p-methoxyamphetamine (PMA) and 4
      methylthioamphetamine (4-MTA). A complete conformational analysis of 3,4
      methylenedioxy-beta-methyl-beta-nitrostyrene (3,4-MD-MeNS), 4-methoxy-beta-methyl
      beta-nitrostyrene (4-MeO-MeNS), 4-methylthio-beta-methyl-beta-nitrostyrene (4-MeS
      MeNS), was carried out by Raman spectroscopy coupled to ab initio MO calculations
      -both complete geometry optimisation and harmonic frequency calculation. The
      Raman spectra show characteristic features of these precursors, which allow their
      ready differentiation and identification. It was verified that the conformational
      behaviour of these systems is mainly determined by the stabilising effect of pi
      electron delocalisation.

PMID- 15508042
TI  - Comparison of diffuse-reflectance absorbance and attenuated total reflectance FT
      IR for the discrimination of bacteria.
AB  - A collection of bacteria belonging to the genus Bacillus were analysed by diffuse
      reflectance absorbance and attenuated total reflectance Fourier transform
      infrared (FT-IR) spectroscopy in the mid-infrared. The diffuse reflectance
      absorbance method is a rapid whole organism fingerprinting method, which
      generates a biochemical profile of the bacteria, where samples are presented to
      the FT-IR spectrometer dried on a metal carrier. The attenuated total reflectance
      FT-IR used in conjunction with a diamond attenuated total reflectance (ATR)
      accessory produces a biochemical profile of the surface chemistry of bacteria
      directly without the need for drying, and has not previously been used in the
      discrimination of bacteria. Principal component, discriminant function and
      hierarchical cluster analysis were performed on the data to discriminate the
      bacteria. The differentiation of the bacteria to species level was observed in
      both analyses however, it was concluded that the ATR FT-IR illustrated better sub
      species differentiation of the microorganisms. This may imply that the total
      biochemical profiling infers discrimination to species level whereas strain
      specific markers are present on the cell surface chemistry.

PMID- 15508043
TI  - Applicability of some mass spectrometric criteria for the confirmation of
      pesticide residues.
AB  - This study was initiated to demonstrate the impact of tolerance intervals
      calculated based on experimental data and standard criteria on the capability to
      detect and identify pesticide residues by GC-MS in plant extract. The tolerance
      intervals specified by the current guidelines and standards (EU, EPA, ISO, EC)
      result in a large number of false negative values. The tolerance intervals
      calculated based on the actually measured ion ratios at 2 different probability
      levels did not provide a better estimate. Based on experimental findings a 2
      phase procedure for confirmation of pesticide residues is recommended. The first
      screening phase comprises identification of those pesticide residues that are
      likely to be present avoiding false negatives as far as possible. Relatively
      large tolerance intervals, +/-30% of absolute ion abundances ratios, have to be
      used at this point. When 2 or 3 selected ion ratios are within the established
      tolerance intervals the residue is confirmed. When the ions detected still
      indicate the possible presence of a residue the result may be reported as
      tentatively identified. However, when the result would lead to regulatory action,
      second confirmatory phase has to be undertaken. This can be achieved with the
      same GC-MS equipment, by injecting matrix-matched standards of the suspected
      analyte, in order to compensate for matrix influence on ion ratios.
      Alternatively, methods using different physico-chemical properties of the
      compound have to be used. The choice of the technique depends on their
      availability, time and cost.

PMID- 15508044
TI  - A new method for the measurement of trace amounts of HONO in the atmosphere using
      an air-dragged aqua-membrane-type denuder and fluorescence detection.
AB  - A new method for the measurement of trace amounts of HONO has been developed.
      Nitrous acid in the ambient air is absorbed in an aqueous solution by an air
      dragged aqua-membrane-type denuder. The absorbed nitrite is reacted with 2,3
      diaminonaphthalene, and the formed 1-naphthotriazol is measured using a
      fluorescence method. The calibration curve of HONO shows a straight line from 0
      to 4000 ppt, and the detection limit is estimated to be 8.1 ppt calculated as
      being three times of the base line noise. The time resolution, which is defined
      as the time required to become a constant value by changing from 0 to ca. 1000
      ppt was 2 min. The present method is not affected by NO(2), NO, SO(2), O(3) NH(3)
      or mixtures of these gases and organic nitrate, organic carboxylic acids,
      alcohols and aldehydes. The determination results of HONO concentrations in the
      ambient air by the present method are in good agreement with those by the annular
      denuder system and the differential optical absorption method.

PMID- 15508045
TI  - Modelling SPME data from kinetic measurements in complex samples.
AB  - The kinetics of the partition process to solid phase microextraction fibres is
      often modelled using a stagnant layer model. Despite its usefulness, in some
      agitation systems such a model cannot be applied because the stagnant layer
      cannot be characterized precisely. Therefore, in this present study an
      alternative approach is introduced. Transport from the bulk medium to the fibre
      coating is simply modelled by a finite mass transfer coefficient instead of
      diffusion through a stagnant water layer surrounding the fibre. Intra-fibre
      transport is described by non-steady diffusion. The model is aimed at the
      analysis of SPME measurements in the kinetic phase for samples including a
      binding matrix. It was validated with experimental results of SPME measurements
      concerning the absorption kinetics of [(3)H]estradiol at different concentrations
      of bovine serum albumin (BSA) as a chemical binding matrix. The model provides
      excellent fits of the experimental data, resulting in an association constant
      (K(a)) of estradiol for BSA of 5.66 x 10(4) M(-1), which is similar to literature
      values and a fibre coating/bulk medium partition coefficient of 5.0 x 10(3). The
      kinetics of extraction were studied with the model, showing that the rate
      limiting step in the extraction process was the diffusion in the fibre. This
      finding rules out the possibility that the presence of the matrix itself in the
      diffusion layer affects the kinetics of estradiol uptake into the SPME fibre.

PMID- 15508046
TI  - An organic-phase optical phenol biosensor coupling enzymatic oxidation with
      chemical reduction.
AB  - This paper presents a recycle amplification optical biosensor to monitor phenol
      in hydrophobic organic solvents. Tyrosinase was first immobilised by entrapping
      it in a copolymer membrane of poly(vinyl alcohol)-hydroxyethyl
      carboxymethylcellulose doped with octadecylsilica particles. The biosensor was
      then constructed by co-mixing small particles of the immobilised tyrosinase with
      the adduct of L-ascorbic acid-poly(vinyl alcohol) (AsA-PVA) in conjunction with
      an optical oxygen transducer. The biosensor was characterised by its amplifying
      response to phenol, stable biocatalytic activity of entrapped-tyrosinase, free of
      interference from o-quinone polymerisation, and large water buffer capacity in
      hydrophobic organic solvents. The working range of the biosensor to phenol was
      0.08-40 mmol dm(-3) in the flow mode. The response times (95%) of the biosensor
      were 4-7 min for phenol. The operational lifetime was more than 40 assays and the
      shelf lifetime of the biosensor was longer than 3 months. The biosensor has been
      successfully applied to quantify the phenol contents in some commercial ointment
      samples.

PMID- 15508047
TI  - A technique for the identification and direct analysis of hexahydro-1,3,5-tris(2
      hydroxyethyl)-s-triazine in metalworking fluids using electrospray-mass
      spectrometry.
AB  - Hexahydro-1,3,5-tris(2-hydroxyethyl)-s-triazine is a widely used biocide in
      metalworking fluids that resists direct quantification in many analytical methods
      due to instability. It can be detected in electrospray-mass spectrometry (ES-MS)
      due to the formation of a charged and relatively stable adduct with the sodium
      ion. This adduct produces a distinct ion spectrum via collision-induced
      fragmentation, which should promote specific detection of the analyte in complex
      matrices. ES-MS detection of the analyte added to, or already present in,
      metalworking fluid samples at microg mL(-1) levels is demonstrated. Parameters
      affecting the formation and detection of the sodium adduct, including choice of
      solvent, alkalinity, and sodium ion level are explored. Linearity of response in
      flow injection mode is demonstrated.

PMID- 15508048
TI  - [The risks associated with the wish for a caesarean section].

PMID- 15508049
TI  - [Prevention of preterm delivery with gestagens].
AB  - Preterm delivery with its short-term and long-term sequealae constitutes a
      serious problem in terms of morbidity, disability and mortality of the newborn
      and cost to the society. The incidence of premature deliveries persists and
      according to the latest national and international reports a tendency for an
      increase has been observed. Therefore, besides screening programmes for the
      detection of vaginal infections one has to look for additional therapeutic
      concepts. According to previous data and recent publications, progesterone
      vaginally and 17alpha-hydroxyprogesterone caproate intramuscularely should be
      considered as possible treatment options for the prevention of preterm delivery
      in high-risk women, with therapy starting in the second trimester.

PMID- 15508050
TI  - [Conservative treatment of puerperal breast abscesses with repeated
      sonographically guided aspirations and oral antibiotic administrations].
AB  - BACKGROUND: Breast abscesses have usually been treated by incision and drainage.
      During the past 10 years conservative treatment with repeated ultrasound-guided
      drainage to evacuate the abscess combined with antibiotic treatment has become a
      valuable alternative. PATIENTS AND METHODS: From 1991 to 2003 the authors treated
      17 patients with puerperal abscess with this method. Under local anesthesia with
      ultrasound guidance a thick needle (preferably a Venflon) is introduced into the
      cavity. The procedure is repeated every two or three days until the ultrasound
      image demonstrates a diameter of the cavity of 1.5 cm or less. The oral
      antibiotic treatment lasts for 6 to 10 days. RESULTS: In 7 cases only one
      puncture was needed, 5 cases needed 2 punctures while 4 women needed 3 or more
      punctures (up to 5). In 16 cases an open drainage could be avoided. One patient
      wanted to discontinue the conservative treatment after the first puncture and
      requested the surgical drainage. CONCLUSIONS: Conservative therapy with
      ultrasound-guided drainage of puerperal breast abscesses can therefore be
      recommended as a standard treatment.

PMID- 15508051
TI  - [Mother-infant Interactions with Very Low Birth Weight multiple newborns (< 1500
      g). A comparison of mother-multiple and mother-single births].
AB  - BACKGROUND: Assisted reproductive techniques and fertility enhancing therapies
      have increased the rate of multiple births and, therefore, the risk of
      prematurity. Our hypothesis is that mothers of preterm multiples are less able to
      provide such enhancing interactions than mothers of preterm singletons, resulting
      in a developmental disadvantage for preterm twins and triplets. PATIENTS AND
      METHODS: Of 77 very low birth weight preterms (VLBW) who were examined
      prospectively with their mothers in a longitudinal study, 35 were multiples and
      42 were singletons. At a corrected age of three months the quality of the mother
      infant interaction with multiples vs. singletons was examined. The Mannheim
      Rating System, a 40-item standardized observation instrument based on a 10 minute
      videotaped sequence of interaction, was used. RESULTS: The analyses showed
      several differences between mother-singleton and mother-multiple interactions.
      Mothers of multiples were less stimulating and reactive and showed less babytalk.
      Multiple infants were also less reactive than singletons. In mother-multiple
      dyads there were less verbal exchanges between mother and child. CONCLUSIONS:
      There are definite differences in mother-multiple compared to mother-singleton
      interactions, so that VLBW multiples may be at even greater risk for negative
      mother-infant interactions than singletons.

PMID- 15508052
TI  - [Maternal postpartum anaemia--tendencies and variability, considering different
      hospital categories--research on the basis of Perinatology in Baden-Wurttemberg].
AB  - BACKGROUND: Postpartum anaemia continues to be the most common puerperal
      complication in Germany. Interest, however, increases in maternal quality of life
      after delivery and with regard to scarce resources in the costs associated with
      anaemia. MATERIAL AND METHODS: With this background, perinatal survey data of
      Baden-Wurttemberg 1998 - 2003 (566,920 pregnancies) were studied regarding
      development and variability of anaemia in pregnancy and puerperium. RESULTS: The
      anaemia rate post-partum increased from 1998 to 2003 (1998 12.2 %, 2003 15.6 %).
      This is a significant trend. The category of small hospital departments, however,
      had lower rates in 2003 than in 1998. Significant differences exist between the
      rates of the hospital categories. High-volume departments show the highest rate
      (e. g., 2003: hospital departments > 1000 deliveries per year 23.2 %, consultant
      departments < 500 deliveries per year 9.4 %). The differences existed throughout
      the observed period and remained significant when all pregnancies with risk
      factors associated with higher blood loss were not taken into account and methods
      of delivery were considered separately. In 2003, anaemia during pregnancy, up to
      then documented for less then 2 % of the pregnancies, showed a much higher rate
      (e. g., high-volume departments: 6-fold higher than in 2002). DISCUSSION: Many
      factors may contribute to these differences, including aspects of obstetrical
      management, volume-outcome associations, and documentation. CONCLUSIONS: Reducing
      interhospital variability includes the option of reducing anaemia rates post
      partum. Analysis and reflection of these results within the departments may
      suggest strategic changes concerning prevention, therapy, obstetric management,
      and workload as well as documentation habits.

PMID- 15508053
TI  - [Does the combination of primary high-frequency oscillation ventilation and
      prophylactic surfactant therapy improve the prognosis for extremely low birth
      weight infants?].
AB  - BACKGROUND: Although animal data show a clear advantage of HFOV compared with CMV
      in the therapy for IRDS, clinical data are still heterogeneous. We have compared
      our clinical results of HFOV with those of CMV to evaluate the potential benefit.
      PATIENTS AND METHODS: During the observation period primary care of all extremely
      low birth weight infants was done in a standardised way with a restricted
      indication for endotracheal intubation. Intubated patients received surfactant
      immediately after intubation. Patients requiring an FiO (2) > 0.4 after
      administration of surfactant received HFOV. RESULTS: 52 patients were included
      into the study. 21 received CMV and 31 received HFOV. There were no differences
      between both groups in mortality and morbidity, but patients in the HFOV group
      were significantly more immature and smaller than those in the CMV group. They
      also had higher CRIB, SNAP and SNAP-PE scores, thus having a much higher risk of
      morbidity and mortality. CONCLUSION: In our study babies who were extremely
      immature and small might have had a profit from the very early administration of
      surfactant and start of HFOV immediately after endotracheal intubation. Similar
      results in other small retrospective analyses and also in animal experiments
      suggest the need for a large randomised controlled trial using early surfactant
      administration and starting HFOV immediately after intubation.

PMID- 15508054
TI  - [Haemolytic disease of the newborn--from a mother with anti-Kell, anti-E and anti
      Vel anti-erythrocyte alloantibodies].
AB  - A grave form of HDN (haemolytic disease of the new-born) is described in female
      twins, caused by Kell, E and Vel isoimmunisation. The weakly vital and anaemic
      new-born babies were hospitalised with signs of respiratory distress on the first
      day of their life after the delivery by Caesarean section in the 38 (th) week of
      pregnancy in the General Hospital Dubrovnik. Already during the first hours of
      their life jaundice developed with a high bilirubin level for their age. The
      direct Coombs' test on the twins and the indirect Coombs' test on the mother were
      positive. Immuno-haematological analysis proved the presence of anti-Kell, anti-E
      and the very rare anti-Vel antibodies in the mother's serum and in the plasma of
      both twins. We had no possibility to obtain appropriate blood for the indicated
      exsanguine transfusion because cross-probes with the accessible blood samples
      were positive. Up to the fourteenth day of life the anaemia deepened and was
      aggravated in one twin, the Kell positive one (phenotype CcDEe,Kk) in relation to
      the other, the Kell negative (phenotype CcDEe,kk) twin. The recovery of the
      female twins started on the 15 (th) day of life, after the transfusion of blood
      (phenotype: 0,ccddee, Vel negative, Kel negative), received from the bank of rare
      blood groups in London. This is the first described case of haemolytic disease of
      the new-born caused by antibodies on the antigen Kell, E and Vel. The low
      frequency of immunisation with rare antigens such as Kell, E and Vel, does not
      exclude the possibility of the occurrence of grave forms of haemolytic disease.
      All pregnant women with a positive indirect Coombs' test should be further immuno
      haematologically tested in order to identify the antibodies type so that the
      treatment of the new-borns could be commenced in time.

PMID- 15508055
TI  - [Surgical treatment of hepatic infections with Echinococcus granulosus].
AB  - INTRODUCTION: Cystic echinococcosis (CE) is a world-wide zoonosis but is
      relatively rare in Western industrial countries. Surgery is the treatment of
      choice. However, the technical procedure varies and evidence-based knowledge is
      fragmentary. Cystectomy and partial resection of the liver (pericystectomy,
      segmental resection, hemihepatectomy) are the procedures under debate. OBJECTIVE:
      We present a descriptive analysis of the patients suffering from CE (anamnesis,
      cyst location, procedures, morbidity, lethality, hospital stay, and long-term
      follow-up). METHODS: A retrospective analysis was made of the medical records and
      questionnaires of patients surgically treated within a period of 16 years at a
      German university hospital. RESULTS: Sixty-four patients had 101 parasitic cysts
      which were treated by 67 operations. The average volume of the cysts was about
      400 ml (range 10 - 2200 ml). Eighty-six cysts were located within the liver and
      15 in extrahepatic sites. The parasitic lesions were removed by hemihepatectomy
      (n = 4), segmental liver resection (n = 9), pericystectomy (n = 24), cystectomy
      (n = 34), and cysto-jejunostomy (n = 1). During the first half of the observation
      period resective procedures were preferred (81 %) whereas during the second half
      cystectomy predominated (82 %). Lethality was 0 %. Postoperative morbidity after
      resective procedures and cystectomy was 47 % and 17 %, respectively. Relapses
      were not observed after cystectomy, but occurred in four cases following
      resective procedures (twice after hemihepatectomy, 4 and 7 years later,
      respectively; once after segmental liver resection and once following cysto
      jejunostomy, both 2 years after the respective procedure). The more extensive the
      surgical procedure the longer was the hospital stay. CONCLUSION: Cystectomy
      should be performed as the procedure of choice because it proved to be safe,
      simple, effective, and meets all criteria of the surgical treatment for hydatid
      disease, i. e., complete elimination of the parasite, no intra-operative spillage
      especially by the use of Aaron's cone, and saving healthy tissue. Pericystectomy
      should be used for peripheral liver cysts only partially surrounded by liver
      tissue.

PMID- 15508056
TI  - [The ultrasound contrast agent levovist helps with the differentiation between
      accessory spleen and lymph nodes in the splenic hilum: a pilot study].
AB  - BACKGROUND: In patients with focal lesions which are isoechogenic to the spleen
      and which are located next to the spleen it is not easy to differentiate between
      lymph nodes and the accessory spleen. Therefore, the aim of this study was to
      evaluate if the color-SAE technique performed after injection of Levovist is able
      to differentiate between accessory spleens and lymph nodes in patients with a
      mass in the hilus of the spleen. METHODS: 12 patients with sonographic proof of a
      hypoechoic mass in the hilus of the spleen were examined (Sonoline-Elegra
      ultrasound system, Siemens, Erlangen, Germany). Color-SAE was performed 10
      minutes after injection of 1 g of Levovist i. v. RESULTS: All patients with
      accessory spleens (n = 7) showed a color-SAE mosaic pattern in the localization
      of the mass comparable to the color-SAE mosaic found in the spleen. In contrast,
      in none of the patients with lymph nodes next to the spleen (n = 5) was a color
      mosaic pattern localized to the mass found, wheras the spleen showed regular
      color-SAE in all cases. CONCLUSION: Color-SAE with Levovist is a new diagnostic
      tool for the differentiation between accessory spleens and lymph nodes.

PMID- 15508057
TI  - [The diagnostic validity of non-invasive pancreatic function tests--a meta
      analysis].
AB  - BACKGROUND: The paper discusses the non-invasive (tubeless) pancreatic function
      tests used to diagnose exocrine pancreatic insufficiency (EI). Studies evaluating
      the diagnostic validity of these tests are integrated into a meta-analysis,
      provided that they comply with the following criteria: The sensitivity (Ss) of a
      test has to be calculated by comparing it with an invasive function test which is
      accepted as the gold standard of pancreatic function diagnostics. Furthermore,
      the test must differentiate between slight (sl), moderate (md) and severe (sv)
      EI. For assessment of the specificity (Sp), the control group should not contain
      healthy persons but rather patients with other gastrointestinal diseases and a
      normal pancreatic function. In the statistical evaluation, each study was
      weighted according to the number of persons included. RESULTS: Tests (n = sum of
      persons included in all analysed studies): Fecal chymotrypsin: Ss (n = 169) 54 %
      (sl EI), 53 % (md EI), 89 % (sv EI), Sp (n = 202) 74 %. NBT-PABA test: Ss (n =
      394) 49 % (sl EI), 64 % (md EI), 72 % (sv EI), Sp (n = 218) 83 %. Pancreolauryl
      test: Ss (n = 320) 63 % (sl EI), 76 % (md EI), 94 % (sv EI), Sp (n = 171) 85 %.
      Fecal elastase-1: Ss (n = 307) 54 % (sl EI), 75 % (md EI), 95 % (sv EI), Sp (n =
      347) 79 %. Additional tests discussed but not included in the meta-analysis were
      fecal fat, (13)C breath tests, amino acid consumption test, serum tests.
      CONCLUSION: None of the non-invasive pancreatic function tests is sensitive
      enough to diagnose reliably a slight to moderate exocrine pancreatic
      insufficiency.

PMID- 15508058
TI  - [S3-Guidelines Conference "Colorectal Carcinoma" 2004].

PMID- 15508059
TI  - Esophagitis in an adolescent patient with Crohn's disease after changing
      treatment from prednisolone to budesonide.
AB  - Studies have demonstrated that budesonide is effective in the treatment of active
      Crohn's disease. Due to its extensive hepatic metabolism, budesonide has much
      lower adverse events compared to prednisolone. Consequently, the low systemic
      availability restricts its application to Crohn's disease of the terminal ileum
      and the colon. Esophageal ulceration is a rare complication of Crohn's disease.
      This article describes the case of a young lady who presented at the age of 16
      with active Crohn's disease of the terminal ileum and the colon without dysphagia
      or pain in the chest. Her disease was successfully treated with prednisolone for
      almost two years. Because of weight gain, acne, and moon face she was switched to
      budesonide. A few days later she presented with intractable pain of the
      esophagus, dysphagia, and inability to eat. Endoscopy demonstrated aphthous
      ulcerations of the esophagus and the histology was compatible with Crohn's
      disease. After two weeks of treatment with prednisolone all symptoms resolved and
      at follow-up gastroscopy ulcers had disappeared.

PMID- 15508060
TI  - [Gastrointestinal stromal tumours (GIST) of the jejunum in a patient with
      neurofibromatosis type 1 (von Recklingshausen's disease)].
AB  - CASE REPORT: A 72-year-old female patient with known neurofibromatosis type 1 was
      admitted to the hospital with symptomatic anaemia and a history of melaena. Upper
      and lower endoscopy did not show any signs of bleeding. Ultrasound and computed
      tomography revealed an abdominal mass. The histological analysis of a US-guided
      puncture showed a mesenchymal tumour with spindle-shaped appearance. Laparotomy
      revealed two jejunal tumours which could be classified as gastrointestinal
      stromal tumours (GIST) by immunohistochemistry. CONCLUSION: Patients with
      neurofibromatosis type 1 have an increased risk of developing gastrointestinal
      tumours including rare types such as GIST. Because the localisation in the small
      intestine by conventional endoscopy can be difficult, further diagnostic means
      such as ultrasound, computed tomography or possibly capsule endoscopy should be
      considered.

PMID- 15508061
TI  - [Chemotherapy for colorectal carcinoma in the elderly].
AB  - With nearly 50 % of all colorectal cancers being diagnosed in patients at the age
      of 70 or above colorectal cancer is a disease of the elderly. In an adjuvant
      setting, fit elderly patients can receive the same benefit from cytotoxic therapy
      as younger patients with an only slightly increased toxicity. In a palliative
      setting, the treatment of elderly patients with respect to clinical endpoints
      such as response, time to progression or overall survival is as effective as in
      their younger counterparts. In clinical studies, older patients are generally
      underrepresented and among the elderly patients involved in clinical studies
      there is a bias towards particularly fit patients. Therefore it is not possible
      to extrapolate the results of many randomized trials to all elderly patients. A
      Comprehensive Geriatric Assessment (CGA) should be applied to detect the
      diversities in the geriatric population. Based on this assessment elderly
      patients classified as suitable for chemotherapy should be enrolled into clinical
      trials for colorectal cancer.

PMID- 15508062
TI  - [CT colonography --"virtual colonoscopy"--a current review].
AB  - This article reviews published data regarding CT colonography and discusses both
      technical and medical aspects of its development over the last 10 years. Although
      colonography can be performed using MRI instead of CT, mainly CT aspects are
      dealt with. The technical development of CT to the current generation of Multi
      detector-row-CT is explained, and the influence of various factors (slice
      thickness, dose, patient preparation, post processing) is discussed. The method
      has a high sensitivity and specificity as well as a high negative predictive
      value for the detection of polyps > or = 1 cm, but is currently still
      insufficient in the detection of polyps < 5 mm. It is a valid alternative after
      incomplete optical colonoscopy and an alternative in patients with "high-risk"
      for conventional endoscopy. In the future it may become an alternative for
      conventional endoscopy in screening programs for colorectal cancer.

PMID- 15508065
TI  - [Re: Perforation of a pancreatic pseudocyst induced by abdominal sonography].

PMID- 15508066
TI  - [What is the cost of sitting in on lectures].

PMID- 15508067
TI  - [Report on the American Gastroenterology Congress. News on gastroenterological
      endoscopy].

PMID- 15508068
TI  - [Infliximab in the treatment of Crohn's disease -- a practical approach.
      Infliximab and chronic Crohn's disease--Consensus statement of the Working Group
      on Chronic Inflammatory Crohn's Diseases of the OGGH].

PMID- 15508069
TI  - Making structures for cell engineering.
AB  - This is a mainly historical account of the events, methods and artifacts arising
      from my collaboration with Adam Curtis over the past twenty years to make
      exercise grounds for biological cells. Initially the structures were made in
      fused silica by photo-lithography and dry etching. The need to make micron-sized
      features in biodegradable polymers, led to the development of embossing
      techniques. Some cells response to grooves only a few tens of nanometers deep-
      this led to a desire to find the response of cells to features of nanometric size
      overall. Regular arrays of such features were made using electron beam
      lithography for definition of the pattern. Improvements were made in the
      lithographic techniques to allow arrays to be defined over areas bigger than 1
      cm2. Structures with microelectrodes arranged inside guiding grooves to allow the
      formation of sparse predetermined networks of neurons were made. It is concluded
      that the creation of pattern, as in vivo, in assemblies of regrown cells in
      scaffolds may well be necessary in advanced cell engineering applications.

PMID- 15508070
TI  - Small is beautiful but smaller is the aim: review of a life of research.
AB  - Background and origins of research of Adam Curtis. One persisting theme has been
      the pursuit of different landscapes at different scales to discover the routes to
      explain how the body is built. His research life fell in a fortunate period
      during which techniques and concepts for investigating structure have improved
      year by year. His most fortunate encounter was with Michael Abercrombie and his
      views on the social behaviour of cells, aims for quantitation, and statistical
      testing. Adam worked in various environments--in turn Geology as an
      undergraduate, Biophysics Ph.D. in a Genetics department and various departments
      in turn from anatomy via zoology to Cell Biology. Adam started his Ph.D. work in
      cell adhesion, studying cell movement, trapping and reaggregation phenomena,
      having an early start from the physico-chemical viewpoint. He made quantitative
      measurements of cell adhesion by kinetic methods. Interference reflection
      microscopy (IRM) and related optical interference techniques were brought into
      the field of biology by him. In turn this led with Chris Wilkinson, a long term
      colleague, to the use of micro- and nanofabrication for biological research.
      Polscope and photoelastic measurements were introduced to biology recently in his
      laboratory. One long term theme has been to map the adhesion of cells to
      substrates to discover contact areas. Early data came from IRM and then TIRF
      (Total Internal Reflection Fluorescence Microscopy) and then from Forster
      Resonance Energy Microscopy (FRET). Another important theme was the time scale
      that needed to be measured--very short indeed in suspension. This was very
      difficult and has only become possible very recently but hydrodynamic calculation
      shows it must be very short. The attractions of the Derjagin-Landau-Verwey
      Overbeek theory (DLVO theory) are that they explain many features of biological
      adhesion. The main test of this theory depends upon the energy of the adhesion at
      various different separation distances between cell and cell or cell and
      substrate. Problems with cell adhesion molecules are discussed. Contact guidance
      of cells by oriented structures and Paul Weiss--Tests with grating replicas
      suggested that topographic rather than biochemical explanations were applicable.
      It became clearer later that this was an area of research waiting for
      microfabrication. Albert Harris influenced me considerably to start thinking
      about mechanical forces produced by cells. Pulling at cells showed effects on the
      cytoskeleton and on cell cycle time. Such thoughts led to a microfabricated
      device for tendon repair. Recent photoelastic measurements with the Polscope have
      allowed much more detailed analysis of the forces between cells. The interesting
      results on microfabricated devices led to work on nanostructures. Results led the
      Glasgow group to consider dimensions of structures and how cells could sense such
      small objects and questions about why order and size may be important.
      Differential protein adsorption onto surfaces seems to provide defective
      explanations of the effects. The results will be discussed in terms of very
      recent theories of cell interaction and cell signals and possible future
      developments will be outlined.

PMID- 15508071
TI  - Introduction: The burden of hepatocellular carcinoma.

PMID- 15508072
TI  - Issues in screening and surveillance for hepatocellular carcinoma.
AB  - Individuals with chronic viral hepatitis and other forms of liver disease are at
      risk for developing hepatocellular carcinoma (HCC). When HCC presents with
      clinical symptoms, the tumor is typically very far advanced and the patient has
      few therapeutic options. Thus, screening and surveillance for HCC would appear to
      very appropriate. However, there is no definitive evidence that surveillance
      improves patient outcomes and current techniques lack sensitivity and
      specificity. Nonetheless, serial measurement of alpha-fetoprotein (AFP) levels in
      serum and hepatic ultrasound have become routine practice, despite a lack of
      evidence of their overall benefit. Clearly, better methods are needed for early
      diagnosis of HCC. Improved technology will ultimately have to be tested for
      improved patient outcome before becoming widely recommended.

PMID- 15508073
TI  - Alpha-fetoprotein and ultrasonography screening for hepatocellular carcinoma.
AB  - Although there is no definitive evidence that hepatocellular carcinoma (HCC)
      screening in high-risk groups improves survival, many physicians screen high-risk
      populations with various strategies. alpha-fetoprotein (AFP) and liver
      ultrasonography (US) are the most widely used tools. AFP sensitivity and
      specificity depend on the cut-off value chosen. In cirrhotic patients, using a
      cut-off level of 20 ng/mL, sensitivity is only around 60% and positive predictive
      value ranges from 9% to 50%, depending on HCC prevalence. Sensitivity and
      specificity are much higher (94.1% and 99.9%, respectively) in hepatitis B
      carriers, but positive predictive value is only 5%. The performance of US as a
      screening tool varies widely depending on the experience of the examiner and the
      technology used. Recent studies generally indicate a 60% sensitivity or higher, a
      specificity greater than 90%, and a positive predictive value of 70%. The cost
      effectiveness of screening strategies using AFP, US, or both have been estimated
      retrospectively or using decision models. In general, HCC screening using both
      AFP and US appears to be of borderline cost effectiveness or not cost effective
      at all. Based on the estimated HCC doubling time, the recommended screening
      interval is 6 months, although a 1-year interval seems as effective. Currently,
      HCC screening with AFP only is not recommended except when US is either not
      available or of poor quality. US seems more efficient as a screening tool.
      Pathology assessment of liver explants in living-donor transplantation programs
      will provide more precise and reliable information regarding the value of AFP and
      US as HCC screening tools.

PMID- 15508074
TI  - Newer markers for hepatocellular carcinoma.
AB  - The incidence of hepatocellular carcinoma (HCC) is increasing worldwide; the
      overall survival of patients with HCC is grim because most patients are diagnosed
      late, when curative treatment is not possible. Cirrhosis is the strongest risk
      factor for the development of HCC. HCC surveillance with alpha-fetoprotein (AFP)
      and ultrasonography has been recommended for persons with cirrhosis. However, AFP
      level is insensitive for the early detection of HCC, and ultrasonography is
      expensive and operator dependent. Clearly, there is a need for novel strategies
      for the early detection of HCC. The ideal biomarker assay for HCC would be
      sensitive, specific, noninvasive, reproducible, inexpensive, and acceptable to
      patients. The Early Detection Research Network of the National Cancer Institute
      has proposed 5 phases for biomarker validation: preclinical exploratory studies,
      clinical assay development for disease, retrospective longitudinal study to
      detect preclinical disease, prospective screening study, and cancer control
      studies. Several biomarkers, such as des-gamma carboxyprothrombin, lens culinaris
      agglutinin-reactive AFP, human hepatocyte growth factor, and insulin-like growth
      factor-1, are promising, but none of these markers has been validated for
      clinical use. Limitations of the current literature include inadequate sample
      size, heterogeneity in biomarker assay methods and result reporting, limited
      analysis of demographics and cause of liver disease as covariates in the
      expression of these markers, and a scarcity of longitudinal studies evaluating
      the ability of biomarkers to detect preclinical disease. There is an urgent need
      for novel biomarkers for the detection of early HCC; the National Cancer
      Institute proposal provides a framework for future validation studies.

PMID- 15508075
TI  - Proteomics for hepatocellular carcinoma marker discovery.
AB  - Refinements of serological markers and screening of patients at high risk for
      developing hepatocellular carcinoma (HCC) may lead to better HCC detection,
      earlier intervention, and successful treatment, improving long-term outcomes.
      Proteomics promises the discovery of biomarkers for early HCC detection and
      diagnosis. Proteomic-based profiling uniquely allows delineation of global
      changes in expression patterns resulting from transcriptional and
      posttranscriptional control, posttranslational modifications, and shifts in
      proteins between cellular compartments. Approaches to that effect include direct
      serum protein profiling and comparative analysis of protein expression in normal,
      precancerous, and early-stage tumor tissues. Identification of panels of tumor
      antigens that elicit a humoral response also may contribute to the discovery of
      new markers for HCC screening and diagnosis. Today, 2-dimensional polyacrylamide
      gel electrophoresis, multidimensional liquid chromatography, mass spectrometry,
      and protein microarrays are among the proteomic tools available for biomarker and
      drug target discovery. We review these technologies and their application to the
      study of HCC. Our objective is to provide a framework for appreciating the
      promise, while at the same time understanding the challenges behind translating
      proteomics discovery into novel diagnostic tests.

PMID- 15508076
TI  - Diagnosis and staging of hepatocellular carcinoma.
AB  - The diagnosis of hepatocellular carcinoma (HCC) includes detection of the index
      lesion, staging of the lesion within the liver, and assessment for extrahepatic
      metastasis. HCC is a highly vascular neoplasm usually arising in a cirrhotic
      liver. Based on this concept, consensus criteria have been developed for the
      radiographic diagnosis of HCC. These include: (1) identification of a mass >2 cm
      in diameter in a cirrhotic liver in 2 imaging modalities, and (2) contrast
      enhancement on computed tomography, magnetic resonance, or angiography. A mass
      lesion within a cirrhotic liver in the presence of a serum alpha-fetoprotein
      level >400 ng/mL also is diagnostic. For lesions <2 cm in diameter, histological
      confirmation is required. Serum markers for the diagnosis of early HCC (<2 cm in
      diameter) have not been established. Staging HCC for metastases is insensitive
      and is based on conventional criteria (eg, pulmonary nodules, skeletal
      metastases, and lymphadenopathy). Additional diagnostic techniques based on
      cytological advances, genomics, and proteomics are needed for the diagnosis and
      staging of this highly malignant neoplasm.

PMID- 15508077
TI  - Computed tomographic imaging of hepatocellular carcinoma.
AB  - The ability of x-ray computed tomography (CT) to detect and characterize liver
      lesions has been one of the most studied issues in radiology during the past 20
      years. Technological advances, combined with increased knowledge about the
      pathophysiological characteristics of these tumors, have dramatically increased
      the ability to detect and characterize large hepatocellular carcinomas (HCCs).
      Nonetheless, detection and characterization of early and small HCC lesions
      remains a difficult task. We review the imaging appearances of HCC on CT and
      discuss the sensitivity and specificity of computed tomographic imaging in
      screening patients with cirrhosis for HCC.

PMID- 15508078
TI  - Magnetic resonance imaging of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC), the most common primary hepatic malignancy,
      usually develops in patients with cirrhosis, growing sequentially from low-grade
      dysplastic nodules to frank malignant HCC. Its recognition is critical because
      curative treatment and prognosis require early diagnosis. Survival in patients
      with HCC relates directly to the number, size, and extent of lesions at
      diagnosis. Imaging of HCC is complicated because the tumor has a varied imaging
      appearance and frequently coexists with other cirrhotic nodules. Magnetic
      resonance imaging (MRI), the best available diagnostic technique, offers good
      contrast resolution and diagnostic sensitivity ranging from 33% to 77%. The main
      difficulty is not in diagnosing large tumors, but rather small tumors (<2 cm),
      because of considerable overlap on imaging between benign (regenerative),
      borderline (dysplastic), and malignant nodules. Increasing degrees of
      histological malignancy are associated with increasing arterialization and loss
      of portal blood supply; therefore, recognition of HCC requires dynamic imaging
      with gadolinium-enhanced T1-weighted sequence. Typically, HCC is a focal lesion
      with high signal intensity on T2-weighted images, variable signal intensity on T1
      weighted images, intense arterial phase enhancement after gadolinium injection,
      and isointensity or hypointensity at the portal venous phase. The sensitivity of
      MRI for detecting small lesions is low, and improvement is still needed. Newer
      contrast agents, higher field strength (3 Tesla) imaging, and perfusion and
      diffusion MRI techniques possibly will provide greater sensitivity and
      specificity for detecting small HCCs in the future.

PMID- 15508079
TI  - Molecular imaging of hepatocellular carcinoma.
AB  - Molecular imaging may be defined as spatially localized and/or temporally
      resolved sensing of molecular and cellular processes in vivo. An imageable
      molecular event may be the result of the overexpression of a gene that produces a
      specific messenger RNA. The overexpressed protein could be an enzyme or could be
      incorporated into cell-surface transporters or receptors. Any step of this
      process is a potential target for molecular imaging. Current molecular imaging
      modalities include magnetic resonance imaging, nuclear imaging, ultrasound, and
      optical imaging. Nuclear medicine has been at the forefront of molecular imaging
      because of the relatively high sensitivity to detect nanomolar or picomolar
      quantities of the radiolabeled imaging probe. Imaging has had a central role in
      the diagnosis of hepatocellular carcinoma (HCC), which is considered the fifth
      most frequent malignancy worldwide. Nuclear imaging was one of the earlier
      modalities used for liver imaging. Traditional tracers included technetium 99m (
      99m Tc) sulfur colloid, gallium 67, and 99m Tc iminodiacetate acid analogues.
      Other less traditional probes include 99m Tc diethylenetriamine pentaacetic acid
      galactosyl-human serum albumin for evaluation of functional liver volume and 99m
      Tc-labeled tetrofosmin and methoxisobutylisonitrile for detecting drug
      resistance. Fluorodeoxyglucose is the most widely used probe for positron
      emission tomography (PET) tumor imaging; however, carbon 11-labeled acetate
      appears to show improved sensitivity and specificity for HCC. Oxygen 15 PET
      imaging allows for the measurement of hepatic and tumor blood flow. Difficulties
      developing specific imaging methods for HCC are caused by the lack of obvious
      specific molecular targets, problems with drug delivery, and poor contrast-to
      noise. No magic molecular imaging method exists today to accurately detect,
      characterize, and monitor HCC in vivo.

PMID- 15508080
TI  - Treatment of hepatocellular carcinoma by percutaneous tumor ablation methods:
      Ethanol injection therapy and radiofrequency ablation.
AB  - In Japan, approximately 30,000 patients died of hepatocellular carcinoma (HCC) in
      2003. Ten percent had hepatitis B virus infection and 80% had hepatitis C virus
      (HCV) infection, indicating that viral hepatitis accounted for >90% of cases of
      HCC. In comparison, only 3% (1.5%, hepatitis B virus; 1.5%, HCV) of the general
      population is infected with these viruses. We treated 1238 patients between 1992
      and the end of 2003 by means of percutaneous tumor ablation (PTA): 524 patients,
      by percutaneous ethanol injection therapy (PEIT); 85 patients, by percutaneous
      microwave coagulation therapy; and 629 patients, by radiofrequency ablation
      (RFA). Three-, 5-, 7-, and 10-year survival rates of the 1238 patients were 69%,
      50%, 34%, and 19%, respectively. When limited to tumors </=3 cm in diameter and
      </=3 in number of cancer nodules (3-3 rule), 5-year survival rates reached 64.7%
      for PEIT. However, to achieve a 40% survival rate in year 5 after PEIT, the
      indication for treatment can be expanded to a 4 (size)-3 (number) rule or 5
      (size)-1 (number) rule. The recent introduction of RFA may further change the
      rules. HCV-related HCC generally develops on the background of advanced
      fibrosis/cirrhosis. An issue of much concern is that it may subsequently recur in
      a location other than that of the primary lesion. We initiated a prospective
      controlled study to evaluate treatment with PTA and interferon. Results suggest
      that if the virus is eradicated, a 5-year survival rate as high as 80% can be
      expected.

PMID- 15508081
TI  - Thermal ablation for hepatocellular carcinoma.
AB  - Thermal ablation, as a form of minimally invasive therapy for hepatocellular
      carcinoma (HCC), has become an important treatment modality. Because of the
      limitations of surgery, the techniques of thermal ablation have become standard
      therapies for HCC in some situations. This article reviews 4 thermal ablation
      techniques-radiofrequency (RF) ablation, microwave ablation, laser ablation, and
      cryoablation. Each of these techniques may have a role in treating HCC, and the
      mechanisms, equipment, patient selection, results, and complications of each are
      considered. Furthermore, combined therapies consisting of thermal ablation and
      adjuvant chemotherapy also show promise for enhancing these techniques. Important
      areas of research into thermal ablation remain, including improving the ability
      of ablation to treat larger tumors, determining the indications for each thermal
      ablation modality, optimizing image guidance, and obtaining good outcome data on
      the efficacy of these techniques.

PMID- 15508082
TI  - Hepatocellular carcinoma: recent trends in Japan.
AB  - During the past 20 years, primary liver cancer, 95% of which is hepatocellular
      carcinoma (HCC), has ranked third in men and fifth in women as a cause of death
      from malignant neoplasm in Japan. The numbers of deaths and death rate from HCC
      showed a sharp increase beginning in 1975. Although both hepatitis B virus (HBV)
      and hepatitis C virus (HCV) infections are important causes, HCV-related HCC has
      accounted for most of the recent increase and now represents 75% of all HCC in
      Japan. Geographically, HCC is more frequent in western than eastern Japan, and
      the death rate of HCC in each prefecture correlates with prevalence of anti-HCV.
      Among patients with HCV-related HCC, a history of blood transfusion was a
      relatively important source of infection in the 1990s, whereas community-acquired
      infections increased after 2000. There was a negative correlation between the
      duration from onset of infection to development of HCC and the age at onset.
      Interferon therapy for chronic hepatitis C has reduced the risk for HCC,
      indicating that early detection of HCV carriers and better treatment will
      contribute to improved outcomes. Nationwide screening for HCV and HBV began in
      2002 in Japan, and reduction of HCC is anticipated. Further research should focus
      on mechanisms of carcinogenesis by HCV and HBV, development of more effective
      treatments, and establishment of early detection and treatment approaches. Better
      understanding of HCC unrelated to HCV and HBV and possibly because of
      steatohepatitis and diabetes should also be a major concern in future studies.

PMID- 15508083
TI  - Chemoembolization for hepatocellular carcinoma.
AB  - Curative therapies for hepatocellular carcinoma (HCC), such as resection, liver
      transplantation, and percutaneous ablation, can be applied in selected patients
      with early tumors; this includes approximately 30%-40% of all cases. More
      advanced stages require local or systemic therapies. Data on the efficacy of
      these treatments are derived from small randomized controlled trials (RCT) and
      meta-analysis. Chemoembolization, a technique combining intra-arterial
      chemotherapy and selected ischemia, has produced modest survival advantages in 2
      RCTs and a meta-analysis, and is currently the mainstay of treatment for these
      stages. The ideal candidates for this option are patients with well-preserved
      liver function (Child-Pugh class A) and multinodular asymptomatic tumors without
      vascular invasion, who constitute less than 15% of the HCC population. In these
      cases, the benefits derived by achieving objective responses (30%-50% of cases)
      are not offset by the deterioration of the liver function. Treatment-related
      mortality is less than 4%. No survival advantages have yet been shown with
      embolization or intra-arterial chemotherapy alone. Further RCTs are needed to
      assess the best chemotherapeutic agent and the ideal retreatment schedule. The
      analysis of efficacy in these trials should be adjusted for prognostic factors,
      such as the presence of symptoms, Child-Pugh class, and segmental vascular
      invasion.

PMID- 15508084
TI  - High-dose proton beam radiotherapy of hepatocellular carcinoma: preliminary
      results of a phase II trial.
AB  - This phase II trial was undertaken to determine the efficacy and toxicity of
      proton beam radiotherapy for patients with locally unresectable hepatocellular
      carcinoma. Cirrhotic patients were eligible if they had a Child-Pugh score of 10
      or less. Eligible patients included those with T 1 -T 3 hepatocellular carcinoma;
      selected T 4 patients also were eligible. Patients with lymph node or distant
      metastases were ineligible. Daily proton beam radiotherapy was directed to the
      liver tumor with an additional 1-2 cm margin. The total dose was 63 cobalt Gray
      equivalents, administered in 15 divided fractions over 3 weeks. Thirty-four
      patients have completed treatment and have been followed up for a minimum of 6
      months, with a median follow-up period of 20 months. The mean age was 65 years,
      and average tumor size was 5.7 cm. Posttreatment toxicity included a small but
      significant decline in albumin levels and increased total bilirubin; 3
      experienced duodenal or colonic bleeding when bowel was immediately adjacent to
      the treated tumor. Two-year actuarial data showed a 75% local tumor control rate
      and an overall survival rate of 55%. Of patients with an elevated pretreatment
      alpha-fetoprotein, 85% were found to have declining alpha-fetoprotein levels from
      a pretreatment mean of 1405 to 35 at 6 months after treatment. Six patients
      underwent liver transplantation between 6 and 16 months after completion of
      radiotherapy with 2 showing no evidence of residual carcinoma within the
      explanted liver. Overall the majority of patients responded to treatment, and the
      therapy was well tolerated.

PMID- 15508085
TI  - Yttrium-90 microspheres for the treatment of hepatocellular carcinoma.
AB  - Unresectable hepatocellular carcinoma is extremely difficult to treat.
      TheraSphere consists of yttrium-90 (a pure beta emitter) microspheres, which are
      injected into the hepatic arteries. This article reviews the safety and survival
      of patients with hepatocellular carcinoma who were treated with yttrium-90
      microspheres. Eighty patients were selected from a database of 108 yttrium-90
      microsphere-treated patients and were staged by using Child-Pugh, Okuda, and
      Cancer of the Liver Italian Program scoring systems. Patients were treated with
      local, regional, and whole-liver approaches. Survival from first treatment was
      analyzed with Kaplan-Meier and Cox regression methods. Adverse events and
      complications of treatment were coded by using the Southwest Oncology Group
      toxicity scoring system. Patients received liver doses ranging from 47 to 270 Gy.
      Thirty-two patients (40%) received more than 1 treatment. Survival correlated
      with pretreatment Cancer of the Liver Italian Program scores ( P = .002), as well
      as with the individual Cancer of the Liver Italian Program components, Child-Pugh
      class, alpha-fetoprotein levels, and percentage of tumor replacement. Patients
      classified as Okuda stage I (n = 54) and II (n = 26) had median survival
      durations and 1-year survival rates of 628 days and 63%, and 384 days and 51%,
      respectively ( P = .02). One patient died of liver failure judged as possibly
      related to treatment. Thus, in selected patients with hepatocellular carcinoma,
      yttrium-90 microsphere treatment is safe and well tolerated. On the basis of
      these results, a randomized controlled trial is warranted comparing yttrium-90
      microsphere treatment with transarterial chemoembolization by using the Cancer of
      the Liver Italian Program system for prospective stratified randomization.

PMID- 15508086
TI  - External beam radiation therapy for hepatocellular carcinoma: potential of
      intensity-modulated and image-guided radiation therapy.
AB  - External beam radiotherapy has historically played a minor role in the primary
      treatment of hepatocellular carcinoma. Although there is evidence for tumor
      response to external beam radiotherapy and despite the fact that a radiation dose
      response relationship has been established, the limited radiation tolerance of
      the adjacent normal liver has prohibited wider use of radiation therapy in this
      disease. Recent technological and conceptual developments in the field of
      radiation therapy-such as intensity-modulated radiation therapy, image-guided
      radiation therapy, and stereotactic body radiation therapy-have the potential to
      improve radiation treatments by conforming the delivered radiation dose
      distribution tightly to the tumor or target volume outline while sparing normal
      liver tissue from high-dose radiation. Image guidance allows for a reduction of
      added (normal tissue) safety margins designed to account for interfraction
      patient and target setup variability, and stereotactic targeting will further
      reduce residual target setup uncertainty. Combining improvements in tumor
      targeting with normal tissue sparing, radiation dose delivery will enable
      clinically effective and safe radiation delivery for liver tumors such as
      hepatocellular carcinoma. This article reviews the role of radiotherapy for
      hepatocellular carcinoma; presents modern radiation therapy modalities and
      concepts such as intensity-modulated, image-guided, and stereotactic body
      radiation therapy; and hypothesizes about their future effect on primary
      treatment alternatives.

PMID- 15508087
TI  - Hepatocellular carcinoma: current management and future trends.
AB  - The hallmarks of hepatocellular carcinoma (HCC) are that it is identified
      clinically at an advanced stage and usually together with cirrhosis. Surgical
      resection has been considered the optimal treatment approach, but only a small
      proportion of patients qualify for surgery, and there is a high rate of
      recurrence. Approaches to prevent recurrence have included chemoembolization
      before and neoadjuvant therapy after surgery, neither of which has proven to be
      beneficial. Liver transplantation has been successful in treating limited-stage
      HCC, affecting cure of both the tumor and underlying cirrhosis. However, only a
      minority of patients with HCC qualify for transplantation. Recently,
      chemoembolization has been shown to prolong survival in selected patients who do
      not qualify for transplantation or resection. Other innovative, relatively
      noninvasive local ablative therapies have been introduced and have been shown to
      be effective in reducing tumor size but not in prolonging survival. Standard
      chemotherapy is poorly tolerated in patients who do not qualify for resection.
      Both doxorubicin and cisplatin are frequently used, but overall response rates
      are low, and neither seems to prolong survival. Prospective, randomized
      controlled trials using current therapies are needed to better define optimal
      management of this important tumor. Most needed, however, are new therapeutic
      agents that are effective against HCC, are noncytotoxic, and are tolerated by the
      typical patient with underlying cirrhosis. Newly emerging agents with promise
      include 90 Y microspheres, antiangiogenesis agents, inhibitors of growth factors
      and their receptors, and K vitamins.

PMID- 15508088
TI  - Antibody-directed therapy for human hepatocellular carcinoma.
AB  - The goals of our research are to develop high-affinity and high-stability
      antibodies and fragments thereof for targeting tumor-specific antigens in an
      attempt to develop new therapeutic agents for human hepatocellular carcinoma
      (HCC). Tumor-associated antigens are excellent targets for drug and gene
      delivery, and offer the advantage of high cellular specificity. We have explored
      the use of a monoclonal antibody (Mab) AF-20 raised against a human hepatoma cell
      line (FOCUS) as a model system. This antibody binds to a 180-kDa homodimeric cell
      surface glycoprotein with high affinity. The antigen is uniformly expressed in
      HCC-derived cell lines and human tumors, including those with distant metastasis.
      There is minimal expression in nontumor tissues, and none detectable in normal
      liver. Because the AF-20 antigen antibody interactions on the cell surface is
      rapidly internalized at 37 degrees C, there is an opportunity to deliver
      cytotoxic payloads to tumor cells. In addition, high-affinity single-chain
      monoclonal antibody fragments (scFv) have been created using a novel yeast
      display system. Drug conjugates with AF-20 monoclonal antibodies have been
      prepared for gene targeting of HCC both in vitro and in vivo using preclinical
      animal model systems. These studies show that it is possible to generate high
      affinity intact scFv antibody fragments that will allow specific tumor targeting
      of adenoviruses containing suicide genes, chemotherapeutic agents such as
      methotrexate, and cytotoxic peptides to produce antitumor effects. Therefore,
      specific antibody targeting of antitumor agents to HCC cells has the potential
      for therapeutic application in this devastating disease.

PMID- 15508089
TI  - Immunotherapeutic strategies for hepatocellular carcinoma.
AB  - There is a continuing need for innovative, alternative therapies for
      hepatocellular carcinoma (HCC). Immunotherapy for cancer is attractive because of
      the exquisite specificity of the immune response. Activation of an HCC-specific
      response can be accomplished by strategies targeting tumor-associated self
      antigens (for example, alpha-fetoprotein [AFP]). Gene array studies have added to
      the list of HCC-specific gene products that can be targeted. Alternatively, the
      immune response can be targeted against viral antigens in those patients infected
      with hepatitis B or C virus. Uncharacterized and mutated antigens can also be
      targeted with whole tumor cell or tumor lysate-based immunization strategies or
      with vectors coding for genes that make the tumor immunogenic, allowing the
      immune system to naturally evolve specificity against immunogenic target
      antigens. Strategies being investigated in animal models include increasing tumor
      immunogenicity by targeting cytokines or costimulatory molecules to tumor;
      immunization with tumor cells fused with antigen-presenting cells; adoptive
      transfer of viral antigen-specific T cells; and targeting AFP-expressing HCC
      cells by DNA, adenovirus, peptide, and dendritic cell (DC) strategies. Strategies
      that have been tested in human clinical trials include adoptive transfer of
      lymphocytes and autologous tumor-pulsed DC as well as 2 AFP-based strategies: AFP
      derived peptides in Montanide and AFP peptides pulsed onto autologous DC. These
      trials, testing novel immune-based interventions in HCC subjects, have resulted
      in immunologic responses and have impacted recurrence and survival in HCC
      subjects.

PMID- 15508090
TI  - Noninvasive thermal ablation of hepatocellular carcinoma by using magnetic
      resonance imaging-guided focused ultrasound.
AB  - A number of minimally invasive methods have been tested for the thermal ablation
      of liver tumors as an alternative to surgical resection. The use of focused
      ultrasound transducers to ablate deep tumors offers the first completely
      noninvasive alternative to these techniques. By increasing the flexibility of
      this technology with modern phased-array transducer design and by combining it
      with magnetic resonance imaging for targeting and online guidance, a powerful
      tool results with the potential to offer treatment to a larger population of
      patients, to reduce trauma to the patient, and to reduce the cost of treatment.
      In this article, we review previous work with focused ultrasound in the liver and
      recent experimental results with magnetic resonance imaging guidance.

PMID- 15508091
TI  - Hepatocellular carcinoma: current surgical management.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common malignancy in the world,
      responsible for 500,000 deaths globally every year. Although HCC is a slow
      growing tumor, it is often rapidly fatal because it is usually not discovered
      until the disease is advanced. HCC occurs primarily in individuals with
      cirrhosis, a condition that increases the risk of performing potentially curative
      surgical therapy. Over the last 2 decades, however, the safety of surgical
      resections has greatly improved because of advances in radiologic assessment,
      patient selection, and perioperative care. As such, the operative mortality rate
      for hepatectomy has decreased from the 10%-20% level seen in the 1980s to less
      than 5% today. The ultimate goal of treatment of HCC is to prolong the quality of
      life by eradicating the malignancy while preserving hepatic function. For
      treatment with a curative intent, the gold standard remains surgical resection,
      by either partial hepatectomy or total hepatectomy followed by liver
      transplantation. Resectability and choice of procedure depend on many factors,
      including baseline liver function, absence of extrahepatic metastases, size of
      residual liver, availability of resources including liver graft, and expertise of
      the surgical team. Patients without cirrhosis can tolerate extensive resections,
      and partial hepatectomy should be considered first. For Child class B and C
      patients with a small HCC, liver transplantation offers the best results, whereas
      partial liver resection is indicated in patients with well-compensated cirrhosis.
      Living donor liver transplantation should be considered using the same criteria
      as that used for cadaveric transplantation.

PMID- 15508092
TI  - Liver transplantation for hepatocellular cancer: the impact of the MELD
      allocation policy.
AB  - Recent reports suggest that selected patients undergoing liver transplantation
      for stage 1-2 hepatocellular cancer (HCC) have an excellent long-term survival
      and a low incidence of recurrence. In the past, over 45% of HCC patients on the
      United Network for Organ Sharing/Organ Procurement Transplantation Network
      waiting list did not receive a donor organ for up to 2 years. This resulted in
      not only a high mortality rate but a high rate of being removed from the waiting
      list because of progression of HCC to advanced stages. The introduction of the
      Model for End-Stage Liver Disease (MELD) allocation policy has had a positive
      effect on HCC liver transplant candidates with the number of patients
      transplanted for HCC significantly increasing over the past several years. In
      addition, waiting time for HCC patients to receive a deceased donor has decreased
      significantly and the number of patients dropping out from the waiting list
      because of advanced stage disease has also decreased. An early assessment of the
      MELD allocation policy suggests that posttransplant survival for HCC patients
      comparing pre-MELD to post-MELD eras is similar. Using the data we have collected
      on the MELD allocation policy, we have already made modifications to the MELD
      allocation policy for HCC patients. It is hoped that through continued data
      collection and assessment, a consensus can be reached to further optimize the use
      of deceased donors in HCC recipients.

PMID- 15508093
TI  - Liver transplantation for hepatocellular carcinoma.
AB  - Because hepatocellular carcinoma (HCC) arises in cirrhotic livers and is often
      multifocal, transplantation seems to be a rational approach. Early results were
      poor, but current restrictive selection criteria can yield excellent results.
      Patients with 1 HCC nodule </=5 cm in diameter, or 2-3 nodules </=3cm, receive
      United Network Organ Sharing priority; nevertheless, dropout from the waiting
      list is common. Predictors of dropout include multiple tumors and tumors with a
      diameter >3 cm. Nonsurgical methods are commonly used to prevent tumor
      progression and thus prevent dropout. Expanding selection criteria results in
      more patients with HCC being cured at the expense of a higher incidence of
      recurrence. Molecular/biologic information is beginning to be incorporated into
      current staging systems in order to better predict HCC recurrence. In considering
      liver transplantation, the impact of the underlying liver disease is an important
      consideration; recurrent hepatitis C after transplant lowers patient survival
      independent of tumor recurrence.

PMID- 15508094
TI  - Hepatocellular carcinoma: recent trends in the United States.
AB  - Hepatocellular carcinoma (HCC) is increasing in frequency in the United States.
      The age-adjusted incidence rates have doubled over the past 2 decades. Similar
      increases have affected the mortality and hospitalization rates. Although there
      has been a small recent improvement in survival, it remains generally dismal
      (median, 8 months). It is estimated that 8500 to 11,500 new cases of HCC occur
      annually in the United States. There are striking differences in the incidence of
      HCC related to age, gender, race, and geographic region. Although it remains an
      affliction of the elderly (mean age, 65 years) population, there has been a shift
      toward relatively younger age cases. Men are affected 3 times more frequently
      than women, Asians are affected 2 times more than blacks, and Hispanics are
      affected 2 times more often than whites. However, the recent increase has
      disproportionately affected white (and Hispanic) men between ages 45 and 65
      years. The temporal changes of risk factors among HCC cases in the United States
      remain unclear. However, available studies indicate that hepatitis C virus (HCV)
      infection acquired 2-4 decades ago explains at least half of the observed
      increase in HCC; HCV-related HCC is likely to continue to increase for the next
      decade. A variable but significant proportion of cases (15% to 50%) do not have
      evidence of the risk factors of viral hepatitis or heavy alcohol consumption. The
      insulin resistance syndrome, manifesting as obesity and diabetes, is emerging as
      a risk factor for HCC in the United States; however, its impact on the current
      trend in HCC remains unclear.

PMID- 15508095
TI  - Living donor liver transplantation for hepatocellular carcinoma.
AB  - The incidence of hepatocellular carcinoma (HCC) is increasing at an alarming rate
      in the United States, such that HCC has become an important indication for liver
      transplantation. The role of liver transplantation in patients with HCC has
      evolved over the past 2 decades, and transplantation has become one of the few
      curative treatment modalities for patients with HCC, especially in selected
      patients with favorable tumors. The advent of living donor liver transplantation
      for adult recipients provides another therapeutic venue, in particular for
      patients with HCC who are disadvantaged by current allocation algorithms for
      grafts from deceased donors. Living donor transplantation may limit the waiting
      time and, as a result, may decrease the progression of disease so that
      intuitively the recurrence rate should be lower than for recipients who wait for
      an organ from a deceased donor. There are limited data on the efficacy of living
      donor liver transplantation in the setting of HCC. Based on a limited cohort of
      patients undergoing transplantation for HCC at Northwestern University Medical
      Center, a higher recurrence rate, stage for stage, was found in recipients whose
      transplants were accelerated ("fast-tracked") by performing a living donor
      transplant, especially in the era in which patients with HCC were disadvantaged
      by the allocation algorithm. Clearly, the role of living donor liver
      transplantation in management of patients with HCC requires prospective direct
      analysis of both recurrence and dropout rates in comparable patient cohorts with
      HCC undergoing either deceased or living donor liver transplantation.

PMID- 15508096
TI  - Hepatocellular carcinoma in the woodchuck model of hepatitis B virus infection.
AB  - The Eastern woodchuck ( Marmota monax ) harbors a DNA virus (Woodchuck hepatitis
      virus [WHV]) that is similar in structure and replicative life cycle to the human
      hepatitis B virus (HBV). Like HBV, WHV infects the liver and can cause acute and
      chronic hepatitis. Furthermore, chronic WHV infection in woodchucks usually leads
      to development of hepatocellular carcinoma (HCC) within the first 2-4 years of
      life. The woodchuck model has been important in the preclinical evaluation of
      safety and efficacy of the antiviral drugs now in use for treatment of HBV
      infection and continues to serve as an important, predictive model for innovative
      forms of therapy of hepatitis B using antiviral nucleosides and immune response
      modifiers alone or in combination. Almost all woodchucks that become chronic WHV
      carriers after experimental neonatal inoculation develop HCC with a median HCC
      free survival of 24 months and a median life expectancy of 30-32 months. The
      woodchuck model of viral-induced HCC has been used effectively for the
      development of new imaging agents for enhancement of detection of hepatic
      neoplasms by ultrasound and magnetic resonance imaging. The chemoprevention of
      HCC using long-term antiviral nucleoside therapy has been shown in the woodchuck,
      and "proof of principal" has been established for some of the innovative,
      molecular methods for treatment of HCC. The model is available for fundamental
      investigations of the viral and molecular mechanisms responsible for
      hepatocarcinogenesis and should have substantial value for future development of
      innovative methods for chemoprevention and gene therapy of human HCC.

PMID- 15508097
TI  - Prevention of hepatitis C virus-related hepatocellular carcinoma.
AB  - The incidence of hepatocellular carcinoma (HCC) is increasing in North America,
      Europe, and Japan, caused largely by the high rates of chronic hepatitis C virus
      (HCV) infection. In such individuals, the risk factors for developing HCC are
      advancing age, male gender, worsening hepatic fibrosis (particularly cirrhosis),
      and greater degrees of hepatic inflammation. Additional, potentially modifiable
      risk factors include coinfection with hepatitis B, excessive alcohol use, iron
      overload, and diabetes/obesity. Thus, approaches to preventing HCC should focus
      on eradicating HCV infection, responsible for the inflammation and fibrosis, and
      also on treating or reducing the modifiable risks, such as through hepatitis B
      vaccination, decreasing alcohol use, phlebotomy for iron overload, and weight
      control and diabetes prevention. These approaches have yet to be proven
      effective. Meta-analyses of standard interferon monotherapy trials in patients
      with HCV-related cirrhosis suggest that interferon has a small but significant
      effect on reducing HCC risk, particularly in those who achieve a sustained
      response. Other studies indicate that the reduction in HCC is greatest if a
      response is achieved before cirrhosis develops. Secondary prevention when HCC has
      been ablated or resected may be partially effected with interferon treatment or
      oral polyprenoic acid. No long-term studies of the effect of the currently
      recommended regimen of peginterferon and ribavirin have been reported, and no
      current trials include untreated control groups. Studies of maintenance
      peginterferon therapy in virological nonresponders are under way in the hope of
      proving that this approach is effective in decreasing the risk of HCC.

PMID- 15508098
TI  - Prevention of hepatitis B virus-related hepatocellular carcinoma.
AB  - The most effective means of preventing hepatitis B virus (HBV)-related
      hepatocellular carcinoma (HCC) is to prevent HBV infection via global vaccination
      of infants. Universal vaccination of newborns has been shown to significantly
      reduce the incidence of HCC among Taiwanese children. Among HBV carriers, the
      incidence of HCC was significantly higher in those who were hepatitis B e antigen
      positive, suggesting that antiviral therapy that results in viral clearance or
      sustained suppression of HBV replication should reduce the incidence of HCC.
      Review of data from >1000 chronic hepatitis B patients who received interferon
      treatment found that interferon has no or minimal overall effect on preventing
      HCC, but a beneficial effect may be attained in responders. The negative results
      are in part related to the small number of patients, short duration of follow-up,
      and low response rate to interferon therapy. Only 1 prospective randomized
      controlled trial of antiviral therapy with incidence of HCC as an endpoint has
      been reported. In this trial, 651 Asian patients with compensated HBV-related
      cirrhosis were randomized to receive lamivudine or placebo. After a median follow
      up of 32 months, HCC was diagnosed in 3.9% lamivudine-treated patients and in
      7.4% placebo controls ( P = 0.047). Further studies using antiviral agents with
      lower risk of drug-resistance are needed to confirm these results. In addition,
      questions on who to treat and how long treatment should be administered must be
      addressed before recommendations on the use of antiviral therapy to prevent HBV
      related HCC can be made.

PMID- 15508099
TI  - Chemoprevention of hepatocellular carcinoma in aflatoxin endemic areas.
AB  - Hepatocellular carcinoma is one of the most common cancers worldwide. Infection
      with hepatitis B virus and exposure to aflatoxins in the diet act synergistically
      to amplify risk. From a public health perspective, hepatitis virus vaccination
      programs and efforts to both reduce aflatoxin exposures and to attenuate the
      toxicological consequences of unavoidable exposures should have major impacts on
      the global incidence of this disease. Experimentally, aflatoxin-induced
      hepatocarcinogenesis can be inhibited by over a score of different
      chemopreventive agents with multiple mechanisms of action. One agent, oltipraz,
      is a potent inducer of phase 2 enzymes involved in the detoxication of
      carcinogens including aflatoxin. A second agent, chlorophyllin, impedes the
      bioavailability of carcinogens by forming molecular complexes and enhances their
      elimination in the fecal stream. This review highlights the findings of recent
      randomized clinical trials with oltipraz and chlorophyllin conducted in
      individuals exposed to dietary aflatoxins and at high risk for development of
      liver cancer. Both chemopreventive agents modulated levels of aflatoxin
      biomarkers in the study participants in manners consonant with protection.
      Although pharmacological approaches establish proof of principle and help
      identify key molecular targets for interventions, food-based approaches that also
      use these molecular targets may be the most practical for widespread application
      in high-risk populations.

PMID- 15508100
TI  - Hepatocellular carcinoma: summary and recommendations.

PMID- 15508101
TI  - Hepatocellular carcinoma in cirrhosis: incidence and risk factors.
AB  - Emerging data indicate that the mortality rate of hepatocellular carcinoma (HCC)
      associated with cirrhosis is rising in some developed countries, whereas
      mortality from non-HCC complications of cirrhosis is decreasing or is stable.
      Cohort studies indicate that HCC is currently the major cause of liver-related
      death in patients with compensated cirrhosis. Hepatitis C virus (HCV) infection
      is associated with the highest HCC incidence in persons with cirrhosis, occurring
      twice as commonly in Japan than in the West (5-year cumulative incidence, 30% and
      17%, respectively), followed by hereditary hemochromatosis (5-year cumulative
      incidence, 21%). In hepatitis B virus (HBV)-related cirrhosis, the 5-year
      cumulative HCC risk is 15% in high endemic areas and 10% in the West. In the
      absence of HCV and HBV infection, the HCC incidence is lower in alcoholic
      cirrhotics (5-year cumulative risk, 8%) and subjects with advanced biliary
      cirrhosis (5-year cumulative risk, 4%). There are limited data on HCC risk in
      cirrhosis of other causes. Older age, male sex, severity of compensated cirrhosis
      at presentation, and sustained activity of liver disease are important predictors
      of HCC, independent of etiology of cirrhosis. In viral-related cirrhosis, HBV/HCV
      and HBV/HDV coinfections increase the HCC risk (2- to 6-fold relative to each
      infection alone) as does alcohol abuse (2- to 4-fold relative to alcohol
      abstinence). Sustained reduction of HBV replication lowers the risk of HCC in HBV
      related cirrhosis. Further studies are needed to investigate other viral factors
      (eg, HBV genotype/mutant, occult HBV, HIV coinfection) and preventable or
      treatable comorbidities (eg, obesity, diabetes) in the HCC risk in cirrhosis.

PMID- 15508102
TI  - Primary liver cancer: worldwide incidence and trends.
AB  - Estimates from the year 2000 indicate that liver cancer remains the fifth most
      common malignancy in men and the eighth in women worldwide. The number of new
      cases is estimated to be 564,000 per year, including 398,000 in men and 166,000
      in women. In high-risk countries, liver cancer can arise before the age of 20
      years, whereas, in countries at low risk, liver cancer is rare before the age of
      50 years. Rates of liver cancer in men are typically 2 to 4 times higher than in
      women. The incidence of primary liver cancer is increasing in several developed
      countries, including the United States, and the increase will likely continue for
      some decades. The trend is a result of a cohort effect related to infection with
      hepatitis B and C viruses, the incidence of which peaked in the 1950s to 1980s.
      In selected areas of some developing countries, the incidence of primary liver
      cancer has decreased, possibly as a result of the introduction of hepatitis B
      virus vaccine. The geographic variability in incidence of primary liver cancer is
      largely explained by the distribution and the natural history of the hepatitis B
      and C viruses. The attributable risk estimates for the combined effects of these
      infections account for well over 80% of liver cancer cases worldwide. Primary
      liver cancer is the first human cancer largely amenable to prevention using
      hepatitis B virus vaccines and screening of blood and blood products for
      hepatitis B and C viruses.

PMID- 15508103
TI  - Genome-scale profiling of gene expression in hepatocellular carcinoma:
      classification, survival prediction, and identification of therapeutic targets.
AB  - The heterogeneous nature of human hepatocellular carcinoma (HCC) has hampered
      both treatment and prognostic predictions. Gene expression profiles of human HCC
      were analyzed to define the molecular characteristics of the tumors and to test
      the prognostic value of the expression profiles. By applying global gene
      expression analyses, including unsupervised and supervised methods, 2 distinctive
      subclasses of HCC that were highly homogeneous for both the underlying biology
      and the clinical outcome were discovered. Tumors from the low survival subclass
      had strong cell proliferation and antiapoptosis gene expression signatures. In
      addition, the low survival subclass displayed higher expression of genes involved
      in ubiquitination and sumoylation, suggesting an etiologic involvement of these
      processes in accelerating the progression of HCC. Genes most strongly associated
      with survival were identified by using the Cox proportional hazards survival
      analysis. This approach identified a limited number of genes that accurately
      predicted the length of survival and provided new molecular insights into the
      pathogenesis of HCC. Future studies will evaluate potential diagnostic markers
      and therapeutic targets identified during the global gene expression studies.
      Furthermore, cross-species similarity of gene expression patterns will also allow
      prioritization of a long list of genes obtained from human gene expression
      profiling studies and focus on genes whose expression is altered during
      tumorigenesis in both species.

PMID- 15508104
TI  - Pathogenesis of hepatitis B virus-related hepatocellular carcinoma: old and new
      paradigms.
AB  - Chronic infection with the hepatitis B virus (HBV) is a major risk factor for
      development of hepatocellular carcinoma (HCC). The pathogenesis of cancer in HBV
      infection has been extensively analyzed, and multiple factors appear to play a
      role. A major factor is chronic inflammation and the effects of cytokines in the
      development of fibrosis and liver cell proliferation. Also important is the role
      of integration of HBV DNA into host cellular DNA, which, in some situations, acts
      to disrupt or promote expression of cellular genes that are important in cell
      growth and differentiation. In addition, expression of HBV proteins may have a
      direct effect on cellular functions, and some of these gene products can favor
      malignant transformation. Several HBV genes have been found in infected tissues
      more frequently than others, including truncated pre-S2/S, hepatitis B X gene,
      and a novel spliced transcript of HBV, referred to as the hepatitis B spliced
      protein. The proteins expressed from these integrated genes have been shown to
      have intracellular activities that may account for their association with HCC,
      including effects on cellular growth and apoptosis. Finally, some patients with
      HCC have no detectable hepatitis B surface antigen in serum but do have low
      levels of HBV DNA in serum and integrated molecules of HBV DNA in tissue. Occult
      HBV infection may account for a proportion of cases of HCC that occur in patients
      without serologic markers for hepatitis B and C and may be a cofactor in HCC in
      patients with chronic hepatitis C who have coexistent occult HBV infection.

PMID- 15508105
TI  - Pathogenesis of hepatitis C-associated hepatocellular carcinoma.
AB  - Epidemiologic, clinical, and virologic data have shown a close association
      between chronic infection with hepatitis C virus (HCV) and the development of
      hepatocellular carcinoma (HCC). In many countries of the developed world, HCV
      infection accounts for more than half of the cases of HCC. HCC usually arises
      after 2-4 decades of infection, typically in the context of an underlying
      cirrhosis. Treatment of hepatitis C with interferon-alfa can lead to sustained
      clearance of HCV, and small prospective studies as well as larger retrospective
      analyses suggest that interferon therapy leads to a decrease in the incidence of
      HCC. Without a reliable tissue culture system or a small animal model of HCV
      infection, analysis of the mechanisms by which HCV leads to cancer has been
      difficult. Nevertheless, both in vitro expression systems and in vivo transgenic
      mice studies suggest that HCV has an inherent carcinogenic potential.
      Understanding the pathogenesis of HCV-associated HCC is important in developing
      effective means of prevention and treatment of this highly malignant form of
      cancer.

PMID- 15508106
TI  - Environmental factors and risk for hepatocellular carcinoma.
AB  - Chronic infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) are
      the most important risk factors for the development of hepatocellular carcinoma
      (HCC) in humans. HBV is the primary cause of HCC in high-risk areas including
      China and Africa, whereas in developed countries such as the United States, HCV
      plays a more prominent role and is at least partially responsible for the
      increase in HCC incidence in this country. Humans are exposed to
      hepatocarcinogenic aflatoxins through ingestion of moldy foods, a consequence of
      poor storage of susceptible grains. Highly exposed populations are primarily in
      sub-Sahara Africa and Asia, where dietary aflatoxins significantly enhance the
      carcinogenic effects of viral hepatitis. Heavy, long-term alcohol use is a risk
      factor for HCC, whereas moderate use (1-3 drinks/day) is not. Constituents of
      cigarette smoke are hepatic carcinogens in animals, and there is mounting
      evidence that the liver is an organ susceptible to tobacco carcinogenicity.
      Diabetic patients are at risk for HCC probably as a result of the hepatic injury,
      fibrosis, and eventual cirrhosis resulting from fatty liver disease. Given the
      current epidemic of obesity and diabetes in the United States, this risk factor
      will be increasingly important. Increased risk for HCC is evident in young
      noncirrhotic users of oral contraceptives in the United States and Europe. In
      summary, risk factors for HCC are identifiable in most patients and primarily are
      associated with chronic hepatic injury.

PMID- 15508107
TI  - Iron, hemochromatosis, and hepatocellular carcinoma.
AB  - Hereditary hemochromatosis (HH) is associated with an increased risk for
      hepatocellular carcinoma (HCC). The risk previously had been estimated to be as
      high as 200-fold increased. Recent studies suggest that the risk for HCC in HFE 
      associated HH may be much lower and occurs predominantly in patients with
      cirrhosis at the time of diagnosis. The risk for HCC also is increased among
      patients with African iron overload and possibly in other iron-loading disorders
      such as homozygous beta thalassemia. The greatly increased iron stores in the
      liver observed in these disorders can stimulate carcinogenesis via both direct
      and indirect pathways. The prevalence of HCC also appears to be higher among
      patients with end-stage liver disease undergoing liver transplantation. It is not
      clear whether mildly to moderately increased hepatic iron stores or HFE mutations
      are associated independently with an increased risk for HCC among patients with
      other types of liver disease. In this article, the incidence and prevalence of
      HCC in patients with HH and other liver diseases associated with iron overload
      are discussed as well as the possible mechanisms for the increased risk for
      hepatic carcinogenesis in these disorders.

PMID- 15508108
TI  - Alcohol and hepatocellular carcinoma.
AB  - More than 18 million adults in the United States abuse alcohol, a prevalence 5
      times higher than that of hepatitis C. Chronic alcohol use of greater than 80
      g/day for more than 10 years increases the risk for hepatocellular carcinoma
      (HCC) approximately 5-fold; alcohol use of less than 80 g/day is associated with
      a nonsignificant increased risk for HCC. The risk for HCC in decompensated
      alcohol induced cirrhosis approaches 1% per year. The risk does not decrease with
      abstinence, and HCC can occur in a noncirrhotic liver. Alcohol use in chronic
      hepatitis C doubles the risk for HCC as compared with the risk in hepatitis C
      alone. Furthermore, there may be synergism between alcohol and hepatitis C in the
      development of HCC, and in these patients HCC may occur at an earlier age and the
      HCC may be histologically more advanced. Studies in the United States and Italy
      suggest that alcohol is the most common cause of HCC (accounting for 32%-45% of
      HCC). The mechanisms by which alcohol causes HCC are incompletely understood, but
      may include chromosomal loss, oxidative stress, a decreased retinoic acid level
      in the liver, altered DNA methylation, and genetic susceptibility. Alcohol use is
      increasing in many countries, suggesting that alcohol will continue to be a
      common cause of HCC throughout the world.

PMID- 15508109
TI  - Obesity and hepatocellular carcinoma.
AB  - Epidemiological studies have shown that obesity is a risk factor for
      hepatocellular carcinoma. Similar studies further indicate that diabetes is also
      a major risk factor. Both obesity and diabetes are frequently associated with
      nonalcoholic fatty liver disease, and case reports have shown progression of
      nonalcoholic fatty liver disease to cirrhosis and hepatocellular carcinoma.
      Although no study has clearly tied all of these variables together, it is likely
      that the association of hepatocellular carcinoma with obesity represents the
      progression of underlying nonalcoholic fatty liver disease to cirrhosis. The
      mechanism most likely involves replicative senescence of steatotic mature
      hepatocytes and compensatory hyperplasia of progenitor (oval) cells as a reaction
      to chronic injury due to ongoing nonalcoholic steatohepatitis and resultant
      hepatic fibrosis. Growth factors associated with chronic inflammation, type 2
      diabetes, and DNA mutations as a result of lipid peroxidation probably play
      significant roles in clonal expansion and hepatocellular carcinoma progression.
      It remains unclear whether cirrhosis is a prerequisite for the development of
      hepatocellular carcinoma or whether hepatocellular carcinoma can develop in fatty
      liver in the absence of cirrhosis. However, well-documented case reports suggest
      that most cases of hepatocellular carcinoma arise in the setting of nonalcoholic
      steatohepatitis with cirrhosis. Whether therapy aimed at nonalcoholic fatty liver
      disease reduces the risk of hepatocellular carcinoma remains to be shown.
      Prophylactic measures and the role of cancer surveillance have not been
      adequately investigated, but current evidence suggests a risk for hepatocellular
      carcinoma in nonalcoholic steatohepatitis-related cirrhosis that rivals that of
      hepatocellular carcinoma in hepatitis C virus-related cirrhosis, particularly in
      older male patients.

PMID- 15508110
TI  - Gene therapy for hematologic disease: Don't throw the baby out with the
      bathwater!

PMID- 15508111
TI  - Genetic manipulation of hematopoietic stem cells.
AB  - Over the past two decades, the ability to transfer genes into hematopoietic stem
      cells (HSCs) has provided new insights into the behavior of individual stem cells
      and offered a novel approach for the treatment of various inherited or acquired
      disorders. At present, gene transfer into HSCs has been achieved mainly using
      modified retroviruses. While retrovirus-based vectors could efficiently transduce
      murine HSCs, extrapolation of these methods to large mammals and human clinical
      trials resulted in very low numbers of gene-marked engrafted cells. In addition,
      in vitro progenitor assays used to optimize gene transfer procedures were found
      to poorly predict the outcome of stem cell gene transfer. The focus rapidly
      turned to the development of superior and more relevant preclinical assays in
      human stem cell gene transfer research. Xenogeneic transplant models and large
      animal transplantation system have been invaluable. The development of better
      assays for evaluating human gene therapy protocols and a better understanding of
      stem cell and vector biology has culminated over the past decade in multiple
      strategies to improve gene transfer efficiency into HSCs. Improved gene transfer
      vectors, optimization of cytokine combination, and incorporation of a recombinant
      fragment of fibronectin during transduction are examples of novel successful
      additions to the early gene transfer protocols that have contributed to the first
      unequivocal clinical benefits resulting from genetic manipulation of HSC.

PMID- 15508112
TI  - Gene therapy for immunodeficiency diseases.
AB  - Primary immunodeficiency diseases represent good targets for hematopoietic stem
      cell-targeted gene therapy. Severe combined immunodeficiencies (SCID) have been
      the first examples of successful gene therapy based on the ex vivo usage of
      retroviral vectors. New advances in the technology of gene transfer should
      further promote gene therapy as a safe and effective therapeutic strategy of
      immunodeficiency diseases.

PMID- 15508113
TI  - Gene therapy for the hemoglobin disorders.
AB  - The hemoglobin disorders of beta-thalassemia and sickle cell disease together
      constitute the most prevalent group of human monogenic diseases. Although
      curative allogeneic stem cell transplantation therapy and palliative therapies
      have been developed for these disorders, the majority of patients still suffer
      significant morbidity and early mortality. The development of therapeutic
      approaches based on genetic manipulation of autologous stem cells therefore
      remains an attractive alternative. In the past 4 years, significant advances have
      been made toward this goal using lentiviral vectors to obtain high-level
      expression of complex globin gene cassettes. Therapeutic correction in murine
      models of both beta-thalassemia and sickle cell anemia has been achieved using
      this approach. These advances, coupled with progress in the ability to achieve in
      vivo selection of genetically modified cells, can now be evaluated in the well
      developed nonhuman primate autologous transplant model. The goal in these studies
      is to provide preclinical safety and efficacy data prior to human clinical trials
      in order to maximize the likelihood of success in the context of an acceptable
      risk to benefit ratio. Here we review progress in each of these areas.

PMID- 15508114
TI  - Gene therapy of the hemophilias.
AB  - Development of hemophilia gene therapy depends on testing gene transfer vectors
      in hemophilic and nonhemophilic animals. Available animal models include factor
      VIII or factor IX knockout mice as well as dogs with spontaneous hemophilia A or
      B. Large animals (particularly dogs) more closely replicate the requirements for
      correction of human hemophilia than do mice. Small animals are more convenient to
      maintain and require significantly less vector for testing than do large animals.
      Nonhemophilic animals (mice or nonhuman primates), whose endogenous factor VIII
      and factor IX complicate analysis of the human proteins, have utility for safety
      testing of vectors; some assays can discriminate between human coagulation
      factors and the endogenous coagulation factors. Most animal models suffer the
      limitations imposed by the immune response to human factor VIII or IX protein.
      Clinical trials have failed to achieve significant factor VIII expression in
      hemophilia A patients, while one clinical trial in hemophilia B patients showed
      only transient therapeutic increments of factor IX expression. Gene therapy
      remains an investigational method with many obstacles to overcome before it can
      be widely used as treatment for hemophilia.

PMID- 15508115
TI  - New paradigms for gene transfer: RNA trans-splicing and small interfering RNA as
      therapeutic strategies.
AB  - If successful, the sustained and regulated expression of therapeutic proteins
      secreted from a variety of tissues would revolutionize the medical treatment of
      hematologic diseases. The current paradigm that has dominated the gene therapy
      field since its inception has been the transfer of complementary DNAs (cDNAs)
      that encode for therapeutic proteins. The transfer of cDNAs can only correct
      autosomal recessive and sex-linked disorders. In most cases, cDNAs are
      constructed that lack their endogenous regulatory elements and therefore lose
      their intrinsic regulation of gene expression. In this article we will describe
      the use of RNA species to either suppress unwanted gene activity or to repair
      defective genes. Examples of RNA inhibition and repair will be discussed.

PMID- 15508116
TI  - Stem cell clonality and genotoxicity in hematopoietic cells: gene activation side
      effects should be avoidable.
AB  - Two serious adverse events involving activation of the LMO2 oncogene through
      retrovirus vector insertion in the otherwise extremely successful first gene
      therapy trial for X-linked severe combined immunodeficieny type 1 (SCID-X1) had
      initially caused widespread concern in the patient and research communities.
      Careful consideration 1 year after diagnosis of the second case still finds 12 of
      the treated patients clearly benefiting from gene therapy (freedom from treatment
      failure, 80%; survival 100%), a situation that should not portend the end of gene
      therapy for this disease, and is, in fact encouraging. While current approaches
      are justified to treat patients with otherwise life-threatening disorders, a
      broad consensus has developed that systematic basic research is required to
      further understand the pathophysiology of these serious adverse events and to
      provide new insights, enabling safer and more effective gene therapy strategies.
      With the continued success of SCID-X1 gene therapy in the majority of patients
      treated, it is of even greater importance to understand exactly which vector
      element or combination of elements predispose to toxicity. An in-depth study of
      the mechanisms behind the activation of the LMO2 and gammac genes will be highly
      instructive for the development of safer procedures and vectors. We summarize the
      central observations, ongoing experimental approaches, new concepts, and
      developments relevant to understanding, interpreting, and eventually overcoming
      the real and perceived obstacles posed by insertional mutagenesis due to gene
      transfer vectors.

PMID- 15508118
TI  - Enzymatic formation of multiple triterpenes by mutation of tyrosine 510 of the
      oxidosqualene-lanosterol cyclase from Saccharomyces cerevisiae.

PMID- 15508119
TI  - Hypothyroidism caused by a nonvisible lingual thyroid.
AB  - BACKGROUND: Lingual thyroid is a developmental anomaly caused by failure of
      migration of the thyroid gland to its normal position in the neck. This anomaly
      is usually manifested in childhood as hypothyroidism or local symptoms. METHODS:
      We present a case of a 32-year-old patient in whom lingual thyroid was diagnosed
      after complaints of a chronic cough. Thyroid-stimulating hormone levels were
      significantly elevated. Sonograms of the neck revealed atrophy of both thyroid
      lobes, with nonhomogeneous consistency and no lymphadenopathy. Technetium-99m
      scan revealed uptake at the tongue base, with no uptake at the neck or other
      locations. RESULTS: L-thyroxine treatment was begun, with progressive decrement
      in thyroid-stimulating hormone levels and cessation of the cough. CONCLUSION:
      This case is unique in both the advanced age of the patient and the unusual
      clinical presentation.

PMID- 15508120
TI  - Simplifying head and neck microvascular reconstruction.
AB  - BACKGROUND: Free-tissue transfer has become the preferred method of head and neck
      reconstruction but is a technique that is considered to use excessive hospital
      resources. METHODS: This study is a retrospective review of 125 consecutive free
      flaps in 117 patients over a 16-month period at a tertiary care university
      hospital. RESULTS: Defects of the oral cavity/oropharynx (60%), midface (9%),
      hypopharynx (15%), or cervical and facial skin (16%) were reconstructed from
      three donor sites: forearm (70%), rectus (11%), and fibula (19%). Microvascular
      anastomoses were performed with a continuous suture technique or an anastomotic
      coupling device for end-to-end venous anastomoses. A single vein was anastomosed
      in 97% of tissue transfers. There were five flaps (4%) requiring exploration for
      vascular compromise, and the overall success rate was 97.6%. The major
      complication rate was 13%. Mean hospital stay was 7 days for all patients and 5
      days for those with cutaneous defects. Combined ablative and reconstructive
      operative times were 6 hours 42 minutes, 7 hours 40 minutes, and 8 hours 32
      minutes for forearm, rectus, and fibular free grafts, respectively. A subset of
      this patient series with oral cavity and oropharynx defects (76 patients; 58%)
      available for follow-up (74 patients) was assessed for deglutition. Forty-three
      patients (58%) had a regular diet, 22 patients (30%) had a limited diet or
      required supplemental tube feedings, and nine patients (12%) were dependent on
      tube feedings with a severely limited diet. CONCLUSIONS: This series suggests
      that most head and neck defects can be reconstructed by use of a simplified
      microvascular technique and a limited number of donor sites. Analysis of
      operative times and length of stay suggest improved efficiency with this approach
      to microvascular reconstruction. Complications and functional results are
      comparable to previously published results.

PMID- 15508121
TI  - Solid-phase synthesis and conformational properties of angiotensin converting
      enzyme catalytic-site peptides: the basis for a structural study on the enzyme
      substrate interaction.
AB  - The solution NMR conformational properties of two angiotensin converting enzyme
      (ACE) Zn catalytic-site 36-residue peptides, with the general sequence
      HEMGHX23EAIGDX3, synthesized through solid-phase 9-fluorenylmethoxycarbonyl
      (Fmoc) chemistry, is reported. The 1H resonance assignment of Zn-bound peptides
      is presented and the characteristic features of the NMR solution models of the
      two ACE Zn(II)-bound peptides are reported. The solid-state and solution
      structures of the ACE C-domain catalytic site are compared while biologically
      important structural similarities and differences of the N- and C-terminal
      catalytic sites are discussed. Additionally, the structural features of the ACE
      substrate, the angiotensin I (AI) decapeptide, are studied using NMR
      spectroscopy, in order to set the structural basis for the ACE-substrate
      interaction in solution.

PMID- 15508122
TI  - Repeated in vivo electrochemical activation and the biological effects of
      microelectromechanical systems drug delivery device.
AB  - The repeated activation of a microelectromechanical systems (MEMS) drug delivery
      device was studied in vivo in rats to examine the effect of implantation on the
      device operation and the effect of electrochemical activation on the inflammatory
      and wound-healing response. The MEMS devices were fabricated from a silicon wafer
      into which reservoirs were etched and covered with gold membranes. The membranes
      were electrochemically removed when an anodic voltage was applied. Devices were
      implanted subcutaneously both with and without stainless steel mesh cages for 4,
      7, 14, 21, or 28 days before activation. Devices were activated every other day
      for five activations. Leukocyte concentrations indicated that both the
      application of voltage and the gold corrosion products elevated the inflammatory
      response which was resolved within 48 h after each activation. The efficiency of
      gold membrane removal was not impaired throughout the implantation, although a
      bimodal distribution of background current densities was observed after long
      implantation times. The thickness of the fibrous capsule surrounding the MEMS
      devices was similar between activated and control devices explanted at each time
      point. It was concluded that the repeated activation of MEMS drug delivery
      devices was successful and the activation produced an acceptable biological
      response that resolved promptly.

PMID- 15508123
TI  - Medial dorsal superficial peroneal nerve studies in patients with polyneuropathy
      and normal sural responses.
AB  - We studied medial dorsal superficial peroneal (MDSP) nerves in 52 patients with
      clinical evidence of mild chronic sensorimotor polyneuropathy and normal sural
      nerve responses, in order to assess the diagnostic sensitivity and usefulness of
      MDSP nerve testing in electrodiagnostic practice. To determine the effect of age
      on MDSP nerve parameters, 98 normal subjects were also examined.
      Electrodiagnostic evaluation involved studies of motor nerve conduction in
      tibial, peroneal, and median nerves; sensory nerve conduction in sural, MDSP,
      median, and radial nerves; tibial and peroneal nerve F waves; H reflexes from the
      soleus muscles; and needle electromyography of gastrocnemius and abductor
      hallucis muscles. Among the patients, 49% had low-amplitude sensory responses in
      MDSP nerves and 57% had either slowing of sensory conduction velocity or no
      sensory responses on proximal stimulation. MDSP nerve amplitude, tibial nerve
      motor velocity, and H reflexes were the most sensitive for detection of mild
      chronic symmetrical axonal sensorimotor polyneuropathy. MDSP nerve testing should
      be included in the routine electrodiagnostic evaluation of patients with
      suspected polyneuropathy and normal sural nerve responses.

PMID- 15508124
TI  - Crystal structure of dehydroquinate synthase from Thermus thermophilus HB8
      showing functional importance of the dimeric state.

PMID- 15508125
TI  - Abnormal spontaneous potentials in distal muscles in animal models of spinal cord
      injury.
AB  - Spontaneous potentials in skeletal muscle distal to human spinal cord injury
      (SCI) have been reported in the literature. Two animal models of SCI were studied
      for the presence of similar potentials. Six rats and two cats with surgical
      transections of the thoracic spinal cord were followed for 4-6 weeks with serial
      electromyography. As a control for the effects of anesthesia and serial testing,
      three intact rats were anesthetized and tested weekly for 4 weeks. In rats with
      spinal cord transection, spontaneous potentials emerged 4-7 days after surgery
      and persisted for the duration of the study (28-32 days). Spontaneous potentials
      were absent in controls at all timepoints. In cats, spontaneous potentials were
      observed 8 days postinjury and gradually diminished, starting at 2 weeks.
      Spontaneous potentials therefore occur after SCI in animals as well as in humans.
      The utilization of animal models will facilitate the understanding of alterations
      that occur distal to spinal cord lesions and affect the function of lower motor
      neurons, leading to peripheral denervation after SCI.

PMID- 15508126
TI  - Impaired glucose tolerance in nondiabetic lumbosacral radiculoplexus neuropathy.

PMID- 15508127
TI  - F-wave latency is the most reproducible NCS parameter in repeated studies
      performed at short intervals.

PMID- 15508128
TI  - Prolonged cold-preservation of nerve allografts.
AB  - The goal of this study was to determine the effect of varying durations of cold
      preservation on the immunogenicity of nerve allografts and their subsequent
      ability to facilitate neuroregeneration across a short nerve gap. Allografts
      preserved for 1, 4, and 7 weeks were compared to untreated allografts and
      isografts. There was a shift from an interferon-gamma-producing cellular response
      (untreated allografts) to an absence of response (7-week cold-preserved
      allografts and isografts). There were no detectable alloantibodies by flow
      cytometry. Histomorphometry distal to the graft showed robust regeneration in the
      isograft and 7-week cold-preserved groups when compared to the untreated
      allograft group. Increasing duration of cold-preservation diminished the cellular
      immune response. This cold-preservation does not preclude subsequent nerve
      regeneration across a short nerve graft. Prolonged cold-preservation of nerve
      allograft tissue could serve as a means to produce unlimited graft material for
      use in peripheral nerve reconstruction.

PMID- 15508129
TI  - Drug related falls: a study in the French Pharmacovigilance database.
AB  - OBJECTIVE: To investigate the risk of falls associated with drugs among the
      French population using data reported to the French spontaneous reporting system
      and recorded in the French Pharmacovigilance database. METHODS: All cases
      including a fall were searched in the French Pharmacovigilance database between
      1995 and 1999. Drugs involved and characteristics of patients were investigated.
      In a second step, we estimated the risk associated with psychotropic and
      cardiovascular drugs in a case/non case comparison, where cases were reports
      including a fall and non cases all other reports. This risk was estimated by
      calculation of crude and age and gender adjusted reporting odds ratios (ROR).
      RESULTS: During this period, 328 reports including a fall were reported (0.4% of
      the database). Patients were female in 70%. Mean age was 76 +/- 18 years.
      Comparisons between cases and non cases showed that cases were more likely to be
      women (OR: 1.9; 95% confidence interval (CI) [1.5-2.4]) and older. After
      adjustment on age and gender, falls remained significantly associated with
      exposure to benzodiazepines (4.7 [3.7-5.9]), imipraminic antidepressants (3.6
      [2.5-5.1]), serotonin reuptake inhibitor (SRI) antidepressants (2.2 [1.5-3.1]) or
      nitrates (1.9 [1.2-2.8]). CONCLUSION: This study confirms that taking
      psychotropic drugs strongly increases the risk of falls. The role of
      cardiovascular drugs (except nitrates) remains not significant when confounding
      factors are taken into account. According to the very high prevalence of
      psychotropic drug use in the French elderly, further study are needed to
      investigate the relative effect of some drugs on falls, like for example SRIs or
      short acting benzodiazepines.

PMID- 15508130
TI  - Discovery of targeting peptides for selective therapy of medullary thyroid
      carcinoma.
AB  - BACKGROUND: Adenovirus efficiently infects a broad range of target cells, thereby
      preventing selective gene transfer. Moreover, several cell types and tissues
      including primary tumors are refractory to adenoviral infection, mainly because
      of low expression levels of coxsackie-adenovirus receptor (CAR). Thus,
      identification of cancer-selective ligands which yield gene transfer to
      neoplastic cells by minimizing transduction of normal cells is a key issue for
      successful cancer therapy. METHODS: We initially analyzed adenoviral receptor
      expression in human medullary thyroid carcinoma (MTC) cells. MTC cell-specific
      peptides were isolated by biopanning a phage display peptide library on cultured
      cancer cells and on tumors in vivo and further characterized. RESULTS: We found
      significant differences in CAR and alphav-integrin protein levels between MTC
      derived TT cells in vitro and established xenograft tumors in mice, indicating a
      lack of alphav-integrin expression on growing tumors. MTC-specific candidates
      were identified by performing three rounds of subtraction. Selected phages showed
      up to 22-fold higher binding efficiency for TT cells when compared with wild-type
      M13 phage or other human cell lines and tumor tissue in vivo. Homing to TT cells
      of the best binding phage was clearly blocked in the presence of specific
      peptide, whereas no phage competition was observed with an unspecific peptide.
      The best binding peptide mediated efficient internalization of the phage.
      Importantly, specific binding and internalization was also mediated by the
      identified peptide within the adenoviral context. CONCLUSIONS: Our results
      indicate that the identified ligand should be suitable to improve selectivity of
      adenoviral gene transfer to medullary thyroid tumors in vivo.

PMID- 15508131
TI  - Theoretical exposure of chronically treated patients to lipid lowering agents.
AB  - PURPOSE: The objective was to analyse the exposure to lipid lowering agents (LLA)
      using the databases of health insurance companies and to appraise its concordance
      with the findings of evidence based medicine. METHODS: Three health insurance
      companies' prescription based databases were analysed in the years 1997-2000. All
      inhabitants in the Czech Republic (CR) have to be insured. The insured person
      with a recorded prescription for LLA in the year of interest was defined as a
      patient, the insured person with a recorded prescription for LLA in the years
      bordering the year of interest was defined as a chronically treated patient. In
      the year of interest the percentage of chronically treated patients without LLA
      medication, with 'very low' (<122 defined daily doses (DDD)/year), 'low' (122-243
      DDD/year) and 'adequate' (>243 DDD/year) consumption was determined. RESULTS:
      During the observed period the total consumption of LLA increased among 450 000
      inhabitants twice (by 109.6%) to 24.8 DDD/1000 inhabitants/day. In 2000 the rate
      of the consumption of statins and fibrates represented 34.2 and 65.6%
      respectively. In 1998 33.5% and in 1999 41.0% of the chronically treated patients
      occurred in the 'adequate' consumption group. CONCLUSIONS: The signals of
      inappropriate drug treatment such as the preferred use of fibrates and low doses
      of LLA prescribed to the Czech population were identified. Conversely, the
      increasing proportion of the chronically treated patients belonging to the group
      with the 'adequate' consumption could be considered as a positive signal.

PMID- 15508132
TI  - Selective prescribing of atypical antipsychotics.
AB  - PURPOSE: The aim of the study was to investigate whether the most recent
      introduced atypical antipsychotics olanzapine and risperidone were preferentially
      prescribed to patients susceptible to develop extrapyramidal side effects (EPS)
      and those not responding adequately to typical antipsychotics. METHODS: Data were
      obtained from the Dutch PHARMO system that includes complete medication and
      hospital admission records of 675 000 residents of 14 Dutch cities. A total
      number of 129 new users of olanzapine and 142 new users of risperidone as well as
      507 new users of typical antipsychotic drugs were identified from our database in
      the period of 1996-1998. The prevalence of markers of EPS, therapy resistance and
      therapy non-compliance were assessed in the period of 1 year prior to a new start
      of an antipsychotic. RESULTS: New use of olanzapine and risperidone was
      significantly associated with previous use of other antipsychotics (odds ratio
      4.0, 95%CI: 2.5-6.7 and odds ratio 3.0, 95%CI: 2.0-4.7, respectively). New use of
      olanzapine and risperidone was also associated with previous use of
      anticholinergic drugs compared to users of typical antipsychotics (over three and
      two times more, respectively). This effect diminished when adjusted for previous
      use of antipsychotics. CONCLUSIONS: In particular olanzapine and also risperidone
      were selectively prescribed to patients formerly treated with other
      antipsychotics and to those susceptible for EPS. If not recognised or controlled
      for, observational studies comparing different antipsychotic drugs may produce
      biased results on efficacy or frequency of side effects for the different types
      of antipsychotics.

PMID- 15508133
TI  - Income related inequality in prescription drugs in Denmark.
AB  - PURPOSE: To examine income-related inequity in utilisation of prescription drugs
      in Funen County, Denmark after a new reimbursement system was implemented.
      METHODS: An individual level prescription database was merged with a health
      survey of 2927 respondents interviewed in 2000 and 2001 about their health status
      and socio-economic and socio-demographic characteristics. An index of horizontal
      inequity was used to estimate the degree of inequity in drug utilisation across
      income groups, using the indirect method of standardisation to control for age,
      gender and health status as a proxy for need. The results were compared to
      estimates from a traditional regression analysis. RESULTS: The least advantaged
      with respect to income consume a bigger share of the prescription drugs than the
      most advantaged. After standardisation for age, gender and health status the
      least advantaged have a lower share of the drug consumption than expected.
      However, traditional regression analysis showed no signs of an income effect on
      the level of consumption of prescription drugs. CONCLUSIONS: The index of
      horizontal inequity suggests that some horizontal inequity favouring the better
      off is present. However, the results deviate from what can be found by
      traditional regression analysis.

PMID- 15508134
TI  - Pattern of drug utilization among hypertensives in a Nigerian teaching hospital.
AB  - PURPOSE: To describe the drug utilization pattern among hypertensive patients in
      a tertiary care setting, assess the short-term outcome of anti-hypertensive drugs
      usage and identify points for future intervention to improve outcomes. METHODS: A
      cross sectional retrospective drug use review was conducted between 1st June and
      31st August 2002 on randomly selected 200 case notes of hypertensive patients at
      a tertiary care facility in South-Western Nigeria. RESULTS: Diuretics were the
      most frequently prescribed anti-hypertensive class (39.4%), followed by centrally
      acting agents (23.3%), calcium channel blockers (21%), angiotensine converting
      enzyme (ACE) inhibitors (8.6%) and beta blockers (1.9%). Aspirin was the most
      frequently prescribed adjoining non-anti-hypertensive drugs (39.7%), followed by
      anxiolytics (23.6%), other non-steroidal anti-inflammatory drugs (NSAIDs)
      (14.8%), metformin (6.7%), glibenclamide (5.9%), paracetamol (5.9%) and Mist.
      Magnesium Trisilicate (3.3%). All patients made out-of-pocket payments for their
      prescribed anti-hypertensive drugs at the study site. Blood pressure control was
      adequate in only 33.9% of patients. There was no significant difference in blood
      pressure control between male and female hypertensives ( p > 0.05). Anti
      hypertensive drugs were changed at least once in 44% of patients and blood
      pressure control was significantly better in patients with at least one change (
      p < 0.05). Adherence with drug therapy was documented as adequate in 82.5% of
      patient. Diabetes mellitus (NIDDM) (39.6%) and osteoarthritis (22.9%) were the
      most frequent co-morbidities. Potential harmful drug interactions were identified
      in 3.8% (49) of patients. CONCLUSIONS: Diuretics and centrally acting agents were
      the most frequently prescribed anti-hypertensive drugs in a tertiary care setting
      in Nigeria. Physicians' prescribing decisions appear significantly influenced by
      cost consideration.

PMID- 15508135
TI  - Characterization of acylated flavonoid-O-glycosides and methoxylated flavonoids
      from Tagetes maxima by liquid chromatography coupled to electrospray ionization
      tandem mass spectrometry.
AB  - Liquid chromatography coupled to negative electrospray ionization (ESI) tandem
      mass spectrometry (MS/MS) employing a triple quadrupole mass spectrometer was
      used in the structural determination of acylated flavonoid-O-glycosides and
      methoxylated flavonoids occurring in Tagetes maxima. The compounds were
      identified by experiments in full scan mode (MS), and tandem mass experiments
      (MS/MS) of precursor ion scan, product ion scan, and neutral loss scan modes. In
      order to characterize the aglycones of the flavonoid glycosides, in-source
      fragmentation of the deprotonated molecule [M-H]- followed by product ion scan of
      the resulting aglycone [A-H]- were performed. This combined approach allowed the
      identification of 51 phenolic compounds, including flavonoid-O-glycosides
      acylated with galloyl, protocatechuoyl, coumaroyl or caffeoyl groups,
      methoxylated flavonoids, and hydroxycinnamic acid and phenolic acid derivatives,
      none of them previously reported in Tagetes maxima.

PMID- 15508136
TI  - Flow injection chemiluminescence determination of dihydralazine sulphate based on
      permanganate oxidation sensitized by rhodamine B.
AB  - A novel flow injection chemiluminescence (CL) method for the determination of
      dihydralazine sulphate (DHZS) is described. The method is based on the CL
      produced during the oxidation of DHZS by acidic permanganate solution in the
      presence of rhodamine B. Rhodamine B is suggested as a fluorescing compound for
      the energy-transferred excitation. The CL emission allows quantitation of DHZS
      concentration in the range 5-800 ng/mL, with a detection limit of 1.9 ng/mL
      (3sigma). The experimental conditions for the CL reaction are optimized and the
      possible reaction mechanism is discussed. The method has been applied to the
      determination of DHZS in pharmaceutical preparations and compares well with the
      high performance liquid chromatography (HPLC) method.

PMID- 15508137
TI  - Automating proteome analysis: improvements in throughput, quality and accuracy of
      protein identification by peptide mass fingerprinting.
AB  - The use of robots has major effects on maximizing the proteomic workflow required
      in an increasing number of high-throughput projects and on increasing the quality
      of the data. In peptide mass finger printing (PMF), automation of steps
      downstream of two-dimensional gel electrophoresis is essential. To achieve this
      goal, the workflow must be fluid. We have developed tools using macros written in
      Microsoft Excel and Word to complete the automation of our platform.
      Additionally, because sample preparation is crucial for identification of
      proteins by matrix-assisted laser desorption/ionization (MALDI) mass
      spectrometry, we optimized a sandwich method usable by any robot for spotting
      digests on a MALDI target. This procedure enables further efficient automated
      washing steps directly on the MALDI target. The success rate of PMF
      identification was evaluated for the automated sandwich method, and for the dried
      droplet method implemented on the robot as recommended by the manufacturer. Of
      the two methods, the sandwich method achieved the highest identification success
      rate and sequence coverage of proteins.

PMID- 15508138
TI  - Use of high-performance liquid chromatography/electrospray ionization collision
      induced dissociation mass spectrometry for structural identification of
      monohydroxylated progesterones.
AB  - For the structural identification of monohydroxylated progesterones synthesized
      by microorganisms, a method was developed using a combination of high-performance
      liquid chromatography and electrospray ionization collision-induced dissociation
      mass spectrometry (HPLC/ESI-CIDMS). The retention times and MS/MS spectra of 11
      different standards at 30 eV were collected and compared. The identification of D
      ring-hydroxylated progesterones (15beta-, 16alpha-, 17alpha- and 21-OH-P) using
      ESI-CIDMS was not possible. However, they were separated chromatographically
      using a 65:35 mixture of water and acetonitrile containing 0.5% acetic acid. The
      other hydroxylated progesterones (2alpha-, 6beta-, 7beta-, 9alpha-, 11alpha-,
      11beta-, and 19-OH-P) could be identified by comparison of eight fragments. The
      complete separation of 11 standards was achieved chromatographically. The
      developed assay was evaluated by the identification of monohydroxylated
      progesterones produced by CYP106A2 from Bacillus megaterium ATCC 13368.

PMID- 15508139
TI  - Use of 18O3-clodronate as an internal standard for the quantitative analysis of
      clodronate in human plasma by gas chromatography/electron ionisation mass
      spectrometry.
AB  - A sensitive and specific method for the quantitative determination of clodronate
      in human plasma is presented. The drug was extracted from plasma by anion
      exchange chromatography and derivatised to the tetra-tert-butyldimethylsilyl
      derivative. 18O3-Clodronate was prepared from unlabeled clodronate and used as an
      internal standard. Gas chromatography/mass spectrometry (GC/MS) under electron
      ionisation conditions was used for quantitative measurement of the drug, using
      m/z 643.16 and 651.17 for target and internal standard, respectively. Calibration
      graphs were linear within the range of 10-1280 ng/mL plasma. Intra-day precision
      was 1.8% (10 ng/mL), 0.5% (40 ng/mL), 1.0% (120 ng/mL), 0.5% (200 ng/mL), 0.5%
      (400 ng/mL) and 2.7% (800 ng/mL) and inter-day variability was found to be 0.7%
      (10 ng/mL), 1.6% (40 ng/mL), 1.3% (120 ng/mL), 2.3% (200 ng/mL), 2.5% (400 ng/mL)
      and 1.2% (800 ng/mL). Intra-day accuracy showed deviations of 0.8% (10 ng/mL),
      0.8% (40 ng/mL), 0.9% (120 ng/mL), 0.9% (200 ng/mL), 1.9% (400 ng/mL) and 0.3%
      (800 ng/mL) and intra-day accuracy was of -1.4% (10 ng/mL), 0.0% (40 ng/mL), 
      0.7% (120 ng/mL), -0.4% (200 ng/mL), -1.2% (400 ng/mL) and -3.3% (800 ng/mL). The
      stable isotope labeled standard was found to be stable under analysis conditions.

PMID- 15508140
TI  - Assay of histamine by nano-liquid chromatography/tandem mass spectrometry with a
      packed nanoelectrospray emitter.
AB  - A nano-liquid chromatographic /tandem mass spectrometric (nanoHPLC/MS/MS) method
      has been developed for the sensitive determination of histamine, a vital
      neurotransmitter. The method involved pre-column derivatization of histamine with
      7-fluoro-4-nitrobenzoxadiazole (NBD-F), thus increasing the hydrophobicity of the
      analyte and allowing it to be retained and stacked on a nanoelectrospay emitter
      packed with C18 reversed-phase particles. Sodium 1-heptanesulfonate, added as an
      ion-pairing reagent in the mobile phase for sample loading, was found to
      facilitate greatly the analyte retention. The packed nanoelectrospray emitter was
      easily prepared using fused-silica capillary of 75 microm i.d., and included
      creating an electrospray emitter tip and then slurry-packing a 5 cm long column
      with 5 microm silica-based particles. After sample loading, the mobile phase was
      changed for separation and a characteristic precursor-to-product ion transition,
      m/z 275 --> 258, was used for the quantification. A linear calibration curve in
      the range from 1.0-100 ng/mL histamine with an r2 value of 0.9995 was obtained.
      The detection limit was estimated to be 0.1 ng/mL histamine in water. In a
      preliminary validation, the method was applied to determine histamine in
      alcoholic beverages and rat brain tissues.

PMID- 15508141
TI  - An NLS peptide covalently linked to linear DNA does not enhance transfection
      efficiency of cationic polymer based gene delivery systems.
AB  - BACKGROUND: Transfection with non-viral gene delivery vectors, such as cationic
      polymers, generally results in low transgene expression in vivo. This is likely
      due to poor cytoplasmic transport and intra-nuclear DNA delivery. METHODS: In
      this study two strategies to improve nuclear import were investigated. Linear DNA
      constructs with or without an NLS peptide were prepared by PCR. Alternatively,
      linear DNA obtained by enzymatic cleavage followed by capping of both ends with
      DNA-hairpins was used. An NLS peptide was attached to one of the capped ends of
      the linear DNA. Both biodegradable (pDMAEAppz) and non-degradable polymers (PEI
      or pDMAEMA) were used to complex the DNA. Several cell types, dividing and non
      dividing, were transfected with the linear DNA constructs containing a SV40
      derived NLS peptide. Nuclear import of the DNA constructs was studied using
      digitonin-permeabilized cells. RESULTS: Linear DNA prepared by PCR proved not
      useful as it was degraded from the 3'end. Linear DNA capped with hairpins was
      more successful with regard to stability. However, Cells transfected with linear
      DNA constructs by electroporation or by using cationic polymers with linear DNA
      containing a NLS peptide, failed to show significantly higher luciferase
      expression levels when compared to cells transfected with plasmid DNA or linear
      DNA without an NLS peptide attached. No nuclear localization was observed in
      digitonin-permeabilized cells. CONCLUSION: Taken together, these data demonstrate
      that this nuclear localisation signal when attached to DNA is neither able to
      improve transfection efficiency of cationic polymers nor the nuclear import of
      the DNA constructs.

PMID- 15508142
TI  - Multi-residue liquid chromatography/tandem mass spectrometry method for the
      detection of non-steroidal anti-inflammatory drugs in bovine muscle: optimisation
      of ion trap parameters.
AB  - A multi-residue liquid chromatography/tandem mass spectrometry method (LC/MS2)
      was developed for the detection of the non-steroidal anti-inflammatory drugs
      acetylsalicylic acid (via the marker residue salicylic acid), flunixin,
      phenylbutazone, tolfenamic acid, meloxicam and ketoprofen, in bovine muscle.
      After extraction of the bovine muscle with acetonitrile, the cleanup was
      performed using a Oasis HLB column. The evaporated eluate was reconstituted and
      analysed by LC/MS2. To obtain optimal detection of salicylic acid and
      phenylbutazone, the ion trap mass spectrometric parameters activation q and
      maximum ion injection time, respectively, were optimised. The activation q for
      salicylic acid was increased to obtain reliable detection of both salicylic acid
      and its product ion. The maximum ion injection time for the time segment
      containing phenylbutazone was decreased since there were not enough scans across
      the chromatographic peak of this compound. The multi-residue method was able to
      detect the different analytes below or at the maximum residue limit (MRL) or
      minimum required performance limit (MRPL) or, in the case of phenylbutazone and
      ketoprofen, at 100 and 20 microg kg(-1), respectively.

PMID- 15508143
TI  - ATCUN-like metal-binding motifs in proteins: identification and characterization
      by crystal structure and sequence analysis.
AB  - The amino terminal Cu(II)- and Ni(II)-binding (ATCUN) motif is a small metal
      binding site found in the N-terminus of many naturally occurring proteins. The
      ATCUN motif has been implicated in DNA cleavage and has been shown to have
      antitumor activity. In proteins, the ATCUN motif is formed from a histidine in
      the third position, its preceding residue and the free N-terminus. Four nitrogen
      atoms from these three residues act as metal ligands. Knowledge of metal-binding
      geometry helps in the design of metal-binding peptides and in understanding of
      the mechanisms of metal-mediated functions. Since the N-terminus region of ATCUN
      containing proteins is highly disordered, no geometrical features can be derived
      from the protein structures. However, the crystal structure of a small metal
      bound ATCUN peptide shows that the nitrogen ligands form a distorted square
      planar geometry. Distance constraints derived from this designed peptide were
      used to search 1949 polypeptide chains to find ATCUN-like motifs in any position
      along the polypeptide chain. Only approximately 1.9% and approximately 0.3% of
      histidines are involved in partial and full ATCUN-like geometric features,
      respectively. These two datasets were compared with the dataset of all
      histidines. None of the ATCUN-like motifs occur in the middle of an alpha-helix
      or a beta-strand. Further sequence analysis revealed total conservation of ATCUN
      histidines in four proteins including the transcription factor TBX3, implicated
      in Ulnar-Mammary Syndrome. Our analysis suggests that the ATCUN-like motif in
      TBX3 is a potential metal-binding site, although a structural role was not
      completely ruled out. Metal-binding activity in TBX3, if confirmed, will help us
      to understand the role of metals in transcriptional regulation and is likely to
      cast light on the causes of some serious genetic disorders. A conformational role
      is suggested for ATCUN-like motifs in other proteins.

PMID- 15508144
TI  - Gene marking of human neural stem/precursor cells using green fluorescent
      proteins.
AB  - BACKGROUND: Ex vivo gene therapy and cell replacement in the nervous system may
      provide therapeutic opportunities for neurodegenerative disorders. The
      development of optimal gene marking procedures for human neural stem cells
      (hNSCs) is crucial for the success of these strategies, in order to provide a
      correct understanding of the biology of transplanted cells. METHODS: hNSCs were
      modified to express various members of the green fluorescent protein family of
      proteins. Both DNA and retroviral expression vectors were used. Cells were
      analyzed for transgene expression under transient and stable expression schemes,
      and in the presence or absence of drug selection, by fluorescence microscopy,
      histochemistry, immunocytochemistry, immunoblotting, RT-PCR and flow cytometry.
      Genetically marked cells were analyzed in vivo after intrastriatal
      transplantation in neonatal rats. RESULTS: Using the same experimental
      procedures, we have compared Aequorea victoria enhanced green fluorescent protein
      (Av-eGFP) and Renilla raniformis GFP (Rh-GFP, h- from humanized) for the purpose
      of gene marking of hNSCs. Our findings revealed practical problems for the
      derivation of stable Av-eGFP-expressing hNSCs, whereas Rh-GFP could be well
      expressed. In a second phase of the study, stable Rh-GFP-expressing clonal hNSCs
      were derived. Rh-GFP did not interfere with the differentiation potential of the
      cells, and expression levels were identical between division and differentiation
      conditions. Thirdly, in vivo, we have confirmed the usefulness of Rh-GFP for the
      study of the transplant performance of hNSCs, and demonstrated that Rh-GFP does
      not interfere with multipotency and differentiation. CONCLUSIONS: Searching for
      suitable and useful reporter genes, we have found that Rh-GFP works efficiently
      for the purpose of stable gene marking of hNSCs, and is highly useful in vivo.
      The nature, properties, and possible side effects of marker genes are discussed,
      since these are important parameters to consider in gene marking studies
      involving hNSCs.

PMID- 15508145
TI  - Quantitative analysis of diffusion tensor orientation: theoretical framework.
AB  - Diffusion-tensor MRI (DT-MRI) yields information about the magnitude, anisotropy,
      and orientation of water diffusion of brain tissues. Although white matter
      tractography and eigenvector color maps provide visually appealing displays of
      white matter tract organization, they do not easily lend themselves to
      quantitative and statistical analysis. In this study, a set of visual and
      quantitative tools for the investigation of tensor orientations in the human
      brain was developed. Visual tools included rose diagrams, which are spherical
      coordinate histograms of the major eigenvector directions, and 3D scatterplots of
      the major eigenvector angles. A scatter matrix of major eigenvector directions
      was used to describe the distribution of major eigenvectors in a defined anatomic
      region. A measure of eigenvector dispersion was developed to describe the degree
      of eigenvector coherence in the selected region. These tools were used to
      evaluate directional organization and the interhemispheric symmetry of DT-MRI
      data in five healthy human brains and two patients with infiltrative diseases of
      the white matter tracts. In normal anatomical white matter tracts, a high degree
      of directional coherence and interhemispheric symmetry was observed. The
      infiltrative diseases appeared to alter the eigenvector properties of affected
      white matter tracts, showing decreased eigenvector coherence and interhemispheric
      symmetry. This novel approach distills the rich, 3D information available from
      the diffusion tensor into a form that lends itself to quantitative analysis and
      statistical hypothesis testing.

PMID- 15508146
TI  - Point spread function mapping with parallel imaging techniques and high
      acceleration factors: fast, robust, and flexible method for echo-planar imaging
      distortion correction.
AB  - Echo-planar imaging (EPI) is an ultrafast magnetic resonance (MR) imaging
      technique prone to geometric distortions. Various correction techniques have been
      developed to remedy these distortions. Here improvements of the point spread
      function (PSF) mapping approach are presented, which enable reliable and fully
      automated distortion correction of echo-planar images at high field strengths.
      The novel method is fully compatible with EPI acquisitions using parallel
      imaging. The applicability of parallel imaging to further accelerate PSF
      acquisition is shown. The possibility of collecting PSF data sets with total
      acceleration factors higher than the number of coil elements is demonstrated.
      Additionally, a new approach to visualize and interpret distortions in the
      context of various imaging and reconstruction methods based on the PSF is
      proposed. The reliable performance of the PSF mapping technique is demonstrated
      on phantom and volunteer scans at field strengths of up to 4 T.

PMID- 15508147
TI  - Localized 7Li MR spectroscopy: in vivo brain and serum concentrations in the rat.
AB  - The brain concentration of lithium (Li) in treated rats was measured using a
      recently developed method based on in vivo 7Li PRESS localized MRS. Comparison
      was made to the corresponding serum concentration at two treatment durations. The
      brain and serum Li concentrations were highly correlated with each other, more so
      than found previously for humans. The brain and serum Li concentrations also
      correlated with dose. Both the brain Li concentration and the serum concentration
      at 16.1 days of treatment correlated with the corresponding measure at 6.6 days.
      After correction of the brain Li concentrations for reduced 7Li MRS visibility,
      the mean brain/serum Li ratio for rats was close to unity, unlike most previous
      values found for humans. However, in some individual cases the ratio deviated
      substantially from the mean, suggesting that serum Li is not always a reliable
      indicator of brain Li.

PMID- 15508148
TI  - Estimating the arterial input function using two reference tissues in dynamic
      contrast-enhanced MRI studies: fundamental concepts and simulations.
AB  - In dynamic contrast-enhanced MRI (DCE-MRI) studies, an accurate knowledge of the
      arterial contrast agent concentration as a function of time is crucial for the
      estimation of kinetic parameters. In this work, a novel method for estimating the
      arterial input function (AIF) based on the contrast agent concentration-vs.-time
      curves in two different reference tissues is described. It is assumed that the
      AIFs of the two tissues have the same shape, and that simple models with two or
      more compartments, and unknown kinetic parameters, can describe their tracer
      concentration-vs.-time curves. Based on the principle of self-consistency, one
      can relate the two tracer concentration-vs.-time curves to estimate their common
      underlining AIF, together with the kinetic parameters of the two tissues. In
      practice, the measured concentration-vs.-time curves have noise, and the AIFs of
      the two tissues are not exactly the same due to different dispersion effects.
      These factors will produce errors in the AIF estimate. Simulation studies show
      that despite the two error sources, the double-reference-tissue method provides
      reliable estimates of the AIF.

PMID- 15508149
TI  - Spatial correlations of laminar BOLD and CBV responses to rat whisker stimulation
      with neuronal activity localized by Fos expression.
AB  - The spatial relationship between a measured fMRI signal and its underlying
      neuronal activity remains unclear. One obstacle is the localization of neuronal
      activity; another is the spatial resolution of fMRI. In the present study, high
      resolution BOLD and CBV fMRI experiments (voxel size: 156 x 156 x 2000 microm3)
      were conducted in the rat whisker barrel cortex at 3 T; neuronal activity across
      cortical layers was mapped using the Fos expression technique. Results show that
      BOLD response is weighted by blood volume and that pixels with high BOLD response
      can be located at the cortical surface or in deep layers, depending on local
      vasculature. In contrast to BOLD response, the pixels with high CBV response were
      consistently clustered in the deep cortical layers. Percentage-CBV change in
      cortical layers IV-V was 7.3 +/- 1.5%, which was significantly higher than in
      layers I-III (4.1 +/- 0.9%) and VI (4.3 +/- 0.7%) (mean +/- SEM). The laminar
      distribution of CBV response correlates well with neuronal activity localized by
      Fos expression. We conclude that neuronal activity can be inferred from CBV fMRI
      data with high spatial accuracy. The data indicate that both intracolumn
      functional connectivity and neurovascular coupling can be studied using CBV fMRI.

PMID- 15508150
TI  - Determining the extent to which delayed-enhancement images reflect the partition
      coefficient of Gd-DTPA in canine studies of reperfused and unreperfused
      myocardial infarction.
AB  - MRI after a constant infusion (CI) of Gd-DTPA has been used to identify the
      extent of myocardial infarction (MI). However, Gd-DTPA-enhanced "viability"
      imaging is more commonly performed with a bolus (for "delayed-enhancement" (DE)
      imaging). This study sought to determine how image delay time and time
      postinfarction influence the assessment of necrosis by DE. Both infusion and DE
      imaging was performed in dogs with reperfused (N = 6) or unreperfused (N = 4) MI.
      Estimates of the partition-coefficient of Gd-DTPA (lambda) with DE were compared
      with those calculated after 60 min of infusion, and the comparisons were repeated
      until 4 (reperfused) or 8 (unreperfused) weeks postinfarction. In reperfused
      animals, the concordance (Rc) between DE and infusion estimates of lambda was >
      0.90 for most image delays > 8 min postinjection, for day 0 through week 3, with
      Rc at day 0 greater than at week 4 (P = 0.022). In unreperfused animals, there
      was an interaction between image delay time and time postinfarction (P < 0.001):
      Rc > 0.90 corresponded to longer image delays at week 1 than at weeks 4-8.
      Therefore, when image delays are selected appropriately, DE images can strongly
      reflect lambda and identify irreversibly injured myocardium.

PMID- 15508151
TI  - Quantification of the 31P metabolite concentration in human skeletal muscle from
      RARE image intensity.
AB  - A method is described for quantifying the cellular phosphorus-31 (31P)
      concentration in human skeletal muscle based on RARE (rapid acquisition with
      relaxation enhancement) image intensities. The 31P concentrations were calculated
      using relaxation rates, RF coil spatial characteristics, and RARE signal
      intensities from foot muscle and an external 31P standard. 31P RARE and 1H T2
      weighted images of the foot muscles in 11 normal subjects were acquired at 3.0 T
      using a double-tuned (31P/1H) birdcage coil. 31P PRESS (point-resolved
      spectroscopy) spectra were acquired to verify the measurable 31P concentrations
      in a multiecho acquisition. The mean measured concentration was 26.4 +/- 3.1 mM
      (mean +/- SD) from RARE signal intensities averaged over the entire imaged foot
      anatomy and 27.6 +/- 4.1 mM for a 3 x 3 pixel region-of-interest measurement. The
      31P RARE image acquisition time was 4 min with a 0.55 cm3 voxel size. These
      results demonstrate that the 31P concentration can be accurately measured
      noninvasively in human muscle from RARE images acquired in short scan times with
      relatively high spatial resolution.

PMID- 15508152
TI  - Perfusion assessment with bolus differentiation: a technique applicable to
      hyperpolarized tracers.
AB  - A new technique for assessing tissue blood flow using hyperpolarized tracers,
      based on the fact that the magnetization of a hyperpolarized substance can be
      destroyed permanently, is described. Assessments of blood flow with this
      technique are inherently insensitive to arterial delay and dispersion, and allow
      for quantification of the transit time and dispersion in the arteries that supply
      the investigated tissue. Renal cortical blood flow was studied in six rabbits
      using a 13C-labeled compound (2-hydroxyethylacrylate) that was polarized by the
      parahydrogen-induced polarization (PHIP) technique. The renal cortical blood flow
      was estimated to be 5.7/5.4 +/- 1.6/1.3 ml/min per milliliter of tissue (mean +/-
      SD, right/left kidney), and the mean transit time and dispersion in the renal
      arteries were determined to be 1.47/1.42 +/- 0.07/0.07 s and 1.78/1.93 +/-
      0.40/0.42 s2, respectively.

PMID- 15508153
TI  - In vivo MRI of embryonic stem cells in a mouse model of myocardial infarction.
AB  - The therapeutic potential of administering stem cells to promote angiogenesis and
      myocardial tissue regeneration after infarction has recently been demonstrated.
      Given the advantages of using embryonic stem cells and mouse models of myocardial
      infarction for furthering the development of this therapeutic approach, the
      purpose of this study was to determine if embryonic stem cells could be loaded
      with superparamagnetic iron oxide (SPIO) particles and imaged in a mouse model of
      myocardial infarction over time using MRI. Mouse embryonic stem cells were
      labeled with SPIO particles. When incubated with 11.2, 22.4, and 44.8 microg
      Fe/ml of SPIO particles, cells took up increasing amounts of iron oxide.
      Embryonic stem cells loaded with SPIO compared to unlabeled cells had similar
      viability and proliferation profiles for up to 14 days. Free SPIO injected into
      infarcted myocardium was not observable within 12 hr after injection. After
      injection of three 10-microl aliquots of 10(7) SPIO-loaded cells/ml into
      infarcted myocardium, MRI demonstrated that the mouse embryonic stem cells were
      observable and could be seen for at least 5 weeks after injection. These findings
      support the ability of MRI to test the long-term therapeutic potential of
      embryonic stem cells in small animals in the setting of myocardial infarction.

PMID- 15508154
TI  - "Squashing peanuts and smashing pumpkins": how noise distorts diffusion-weighted
      MR data.
AB  - New diffusion-weighted imaging (DWI) methods, including high-b, q-space, and high
      angular resolution MRI methods, attempt to extract information about non-Gaussian
      diffusion in tissue that is not provided by low-b-value (b approximately 1000 s
      mm(-2)) diffusion or diffusion tensor magnetic resonance imaging (DT-MRI).
      Additionally, DWI data with higher spatial resolution are being acquired to
      resolve fine anatomic structures, such as white matter fasciculi. Increasing
      diffusion-weighting or decreasing voxel size can reduce the signal-to-noise ratio
      so that some DWI signals are close to the background noise level. Here we report
      several new artifacts that can be explained by considering how background noise
      affects the peanut-shaped angular apparent diffusion coefficient (ADC) profile.
      These include an orientationally dependent deviation from Gaussian behavior of
      the ADC profile, an underestimation of indices of diffusion anisotropy, and a
      correlation between estimates of mean diffusivity and diffusion anisotropy. We
      also discuss how noise can cause increased gray/white matter DWI contrast at
      higher b values and an apparent elevation of diffusion anisotropy in acute
      ischemia. Importantly, all of these artifacts are negligible in the b-value range
      typically used in DT-MRI of brain (b approximately 1000 s mm(-2)). Finally, we
      demonstrate a strategy for ameliorating the rectified noise artifact in data
      collected at higher b values.

PMID- 15508155
TI  - Computational cardiac anatomy using MRI.
AB  - Ventricular geometry and fiber orientation may undergo global or local remodeling
      in cardiac disease. However, there are as yet no mathematical and computational
      methods for quantifying variation of geometry and fiber orientation or the nature
      of their remodeling in disease. Toward this goal, a landmark and image intensity
      based large deformation diffeomorphic metric mapping (LDDMM) method to transform
      heart geometry into common coordinates for quantification of shape and form was
      developed. Two automated landmark placement methods for modeling tissue
      deformations expected in different cardiac pathologies are presented. The
      transformations, computed using the combined use of landmarks and image
      intensities, yields high-registration accuracy of heart anatomies even in the
      presence of significant variation of cardiac shape and form. Once heart anatomies
      have been registered, properties of tissue geometry and cardiac fiber orientation
      in corresponding regions of different hearts may be quantified.

PMID- 15508156
TI  - RF-induced temperature elevation along metallic wires in clinical magnetic
      resonance imaging: influence of diameter and length.
AB  - With the development of interventional MRI, heating of biological tissues along
      the metallic wires in the MRI scanner has become an important issue. To assess
      thermal response to RF exposure during MRI, we studied the temperature elevation
      near nonmagnetic metallic wires. All tests were performed on a 1.5 T clinical
      scanner. Four experiments were conducted to investigate the effects of the wire
      diameter, the excitation flip angle, the temperature distribution along the wire,
      and the wire length. Electromagnetic simulations of the experimental setup were
      made with the use of commercial method of moments (MoM) software and numerical
      simulations of Hallen's equations. Comparisons between measured and calculated
      values of the electric field are presented. This study demonstrates that 1)
      temperature decreases with the diameter of the wire,2) temperature increases
      quadratically with the excitation flip angle, 3) heating occurs not only at the
      tip but also along the wire, and 4) the heating peaks are not obtained for the
      classical resonant length multiple of lambda/4 (where lambda is the RF field
      wavelength). In addition, significant and rapid heating increases were observed
      in the close vicinity of the wire.

PMID- 15508157
TI  - On the nature of the NAA diffusion attenuated MR signal in the central nervous
      system.
AB  - In the brain, on a macroscopic scale, diffusion of the intraneuronal constituent
      N-acetyl-L-aspartate (NAA) appears to be isotropic. In contrast, on a microscopic
      scale, NAA diffusion is likely highly anisotropic, with displacements
      perpendicular to neuronal fibers being markedly hindered, and parallel
      displacements less so. In this report we first substantiate that local anisotropy
      influences NAA diffusion in vivo by observing differing diffusivities parallel
      and perpendicular to human corpus callosum axonal fibers. We then extend our
      measurements to large voxels within rat brains. As expected, the macroscopic
      apparent diffusion coefficient (ADC) of NAA is practically isotropic due to
      averaging of the numerous and diverse fiber orientations. We demonstrate that the
      substantially non-monoexponential diffusion-mediated MR signal decay vs. b value
      can be quantitatively explained by a theoretical model of NAA confined to an
      ensemble of differently oriented neuronal fibers. On the microscopic scale, NAA
      diffusion is found to be strongly anisotropic, with displacements occurring
      almost exclusively parallel to the local fiber axis. This parallel diffusivity,
      ADCparallel, is 0.36 +/- 0.01 microm2/ms, and ADCperpendicular is essentially
      zero. From ADCparallel the apparent viscosity of the neuron cytoplasm is
      estimated to be twice as large as that of a temperature-matched dilute aqueous
      solution.

PMID- 15508158
TI  - Dynamic lung morphology of methacholine-induced heterogeneous
      bronchoconstriction.
AB  - Hyperpolarized (HP) 3helium (3He) dynamic MRI was used to investigate airway
      response in rats following intravenous (i.v.) bolus administration of a
      contractile agent, methacholine (MCh). The method provides direct visualization
      of the ventilated regions within the lung. Heterogeneous bronchoconstriction
      following the i.v. MCh injection was evident using this technique. These 3He
      dynamic lung images revealed that the inspired fresh air was shunted to the less
      constricted regions after the MCh challenge in a similar manner as described by
      Laplace's relationship for the stability between adjacent alveoli. The airways in
      the more-constricted regions became nearly closed, resulting in air trapping,
      while the airways in the less-constricted regions remained effectively open,
      leading to overinflation. These data suggest a lung model of airway constriction
      partitioned into ventilated and nonventilated regions. These nonventilated
      regions are heterogeneously distributed in the lung and this distribution cannot
      be deduced from spirometric measurement of the whole lung. We demonstrate that a
      combination of functional 3He images and anatomical 1H images provide an
      effective method to diagnose regional lung abnormalities in rats.

PMID- 15508159
TI  - Correction of high-order eddy current induced geometric distortion in diffusion
      weighted echo-planar images.
AB  - Diffusion-weighted images acquired with the echo-planar imaging technique are
      highly sensitive to eddy current induced geometric distortions that vary with the
      magnitude and direction of the diffusion sensitizing gradients. Such distortions
      cause misalignment of images acquired with different diffusion strengths and
      orientations. This in turn can result in errors when calculating maps of the
      apparent diffusion coefficient and diffusion tensor. Previous correction methods
      either require separate calibration data or only deal with low-order errors. In
      this study, we demonstrate a method that can correct for higher-order errors. The
      method relies on collecting pairs of images with diffusion sensitizing gradients
      reversed. This paired data are first corrected for shifts and linear distortion
      and then combined to cancel higher-order errors. All acquired data contribute to
      the final results. The method has been tested by simulation, on phantoms, on
      adult volunteers, and on neonatal brain examinations.

PMID- 15508160
TI  - Intravoxel distribution of DWI decay rates reveals C6 glioma invasion in rat
      brain.
AB  - The hypothesis was tested that the intravoxel distribution of water diffusion
      rates, as measured with a stretched-exponential model of diffusion-weighted
      imaging (DWI), is a marker of brain tumor invasion. Eight rats underwent
      intracerebral inoculation of C6 glioma cells. In three rats, cells were labeled
      with a fluorescent dye for microscopy. One rat was inoculated with a saline
      solution, and five more rats were imaged without inoculation as controls. Five
      healthy uninoculated rats were also imaged. DWI was performed 14-15 days after
      inoculation, with diffusion-weighting factor b = 500 to 6500 sec/mm2, and the
      resulting signal attenuation was fitted with the stretched-exponential model. The
      heterogeneity index values were significantly lower (P < 0.05) in the peritumor
      ROI than in normal gray matter and significantly higher than in normal white
      matter. The distributed diffusion coefficient values were significantly lower
      than in normal white matter or normal gray matter. Fluorescence microscopy
      confirmed the presence of tumors in the peritumor region that could be
      histologically distinguished from the main tumor mass. There was no change in
      proton density or T2-weighted images in the peritumor region, making vasogenic
      edema unlikely as a source of contrast. It is therefore thought that the
      heterogeneity parameter alpha is a marker of brain tumor invasion.

PMID- 15508161
TI  - Free-breathing radial acquisitions of the heart.
AB  - There is considerable interest in performing free-breathing acquisitions of the
      heart in order to obtain high-quality images without the need for multiple, long
      breathholds. In this article a 3D motion-correction method is described that is
      based on image registration of in-plane data and through-plane slice tracking. A
      number of fast radial undersampled images are acquired, each of which is free of
      motion artifacts. Initially, in-plane translational and rotational motion between
      each image was corrected before combining the data to give a fully sampled image.
      At the next stage, correction of in-plane deformation, in addition to
      translations and rotations, was performed in the image domain. Through-plane
      translational motion was compensated using a navigator echo to move the
      acquisition plane. Using this method, information on the motion of the heart was
      captured at the same time as acquiring the image data. No motion model,
      assumptions about the motion, or training data are required. The method is
      demonstrated on phantom data and cardiac images acquired on free-breathing
      volunteers.

PMID- 15508162
TI  - On the influence of training data quality in k-t BLAST reconstruction.
AB  - This work investigated how the quality of prior information (i.e., data acquired
      during the training stage) influences k-t BLAST reconstruction. The impact of
      several factors, such as the amount of training data, the presence of spatial
      misregistration in the training data, and the effects of filtering, was
      investigated with simulations and in vivo data. It is shown that k-t BLAST
      outperforms sliding window reconstruction, even with very limited training data.
      By increasing the amount of training data, reconstruction error continues to
      decrease, albeit by a diminishing amount. However, an increased amount of
      training data also increases susceptibility to misregistration of the training
      data. Filtering of the training data with the goal of reducing truncation
      artifacts had only minor impact on reconstruction errors. Considering the balance
      among obtaining the most benefit from the training data, minimizing
      susceptibility to misregistration, and keeping data acquisition to a minimum, it
      is concluded that in cardiac imaging the training datasets should be limited to
      10-20 profiles in k-space for a typical field of view. The training data may be
      acquired in a separate breathhold without much penalty, if care is taken to
      minimize misregistration, such as with a navigator.

PMID- 15508163
TI  - Reduction of residual dipolar interaction in cartilage by spin-lock technique.
AB  - The influence of radiofrequency (RF) spin-lock pulse on the laminar appearance of
      articular cartilage in MR images was investigated. Spin-lock MRI experiments were
      performed on bovine cartilage plugs on a 4.7 Tesla small-bore MRI scanner, and on
      human knee cartilage in vivo on a 1.5 Tesla clinical scanner. When the normal to
      the surface of cartilage was parallel to B0, a typical laminar appearance was
      exhibited in T2-weighted images of cartilage plugs, but was absent in T1rho
      weighted images of the same plugs. At the "magic angle" orientation (when the
      normal to the surface of cartilage was 54.7 degrees with respect to B0), neither
      the T2 nor the T1rho images demonstrated laminae. At the same time, T1rho values
      were greater than T2 at both orientations throughout the cartilage. T1rho
      dispersion (i.e., the dependence of the relaxation rate on the spin-lock
      frequency omega1) was observed, which reached a steady-state value of close to 2
      kHz in both parallel and magic-angle orientations. These results suggest that
      residual dipolar interaction from motionally-restricted water and relaxation
      processes, such as chemical exchange, contribute to T1rho dispersion in
      cartilage. Further, one can reduce the laminar appearance in human articular
      cartilage by applying spin-lock RF pulses, which may lead to a more accurate
      diagnosis of degenerative changes in cartilage.

PMID- 15508164
TI  - Field-of-view limitations in parallel imaging.
AB  - Parallel imaging is one of the most promising developments in recent years for
      the acceleration of MR acquisitions. One area of practical importance where
      different parallel imaging methods perform differently is the manner in which
      they deal with aliasing in the full-FOV reconstructed image. It has been reported
      that sensitivity encoding (SENSE) reconstruction fails whenever the reconstructed
      FOV is smaller than the object being imaged. On the other hand, generalized
      autocalibrating partially parallel acquisition (GRAPPA) has been used
      successfully to reconstruct images with aliasing in the reconstructed FOV, as in
      conventional imaging. The disparate behavior of these methods can be easily
      demonstrated by a few simple illustrative examples. Additional in vivo examples
      using GRAPPA and modified SENSE (mSENSE) make this distinction clear. These
      experiments demonstrate that SENSE fails to reconstruct correct images when coil
      sensitivity maps are used that do not automatically account for the object size
      and therefore the aliasing in the reconstructed images. However, with the use of
      aliased high-resolution coil sensitivity maps, accurate SENSE reconstructions can
      be generated. On the other hand, GRAPPA produces images with an aliasing
      appearance that is exactly as would be expected from normal nonaccelerated
      acquisitions. An understanding of these effects could potentially lead to fewer
      operator-dependent errors, as well as a better understanding of the differences
      between the underlying reconstruction processes.

PMID- 15508165
TI  - Phantom design method for high-field MRI human systems.
AB  - A phantom design method suitable for high-field MRI based on the RF field wave
      characteristics of sample and experimental validations at 7.0 T and 3.0 T are
      presented. The RF field distribution in a phantom with a given RF coil system is
      primarily determined by the sample size relative to the wavelength inside the
      sample, and the ratio between the displacement and conduction currents.
      Experimental results demonstrate that the MR image intensity patterns associated
      with wave behavior in human samples at a given field strength can be reproduced
      with a phantom at the same or different field strengths once the dimension and
      penetration constant are scaled by the corresponding wavelength in the sample
      medium.

PMID- 15508166
TI  - Human myeloperoxidase: a potential target for molecular MR imaging in
      atherosclerosis.
AB  - Plaque rupture in atherosclerotic disease is the major cause of morbidity and
      correlates well with myeloperoxidase (MPO) secretion by activated neutrophils and
      macrophages in humans. We hypothesized that paramagnetic electron donor compounds
      that rapidly oxidize and polymerize in the presence of MPO could be designed to
      enable imaging of local MPO activity levels in arterial segments at risk. Several
      potential substrates for MPO were synthesized and tested. One lead compound
      consisting of a covalent conjugate of GdDOTA and serotonin (3-(2-aminoethyl)-5
      hydroxyindole) was efficiently polymerized in the presence of human neutrophil
      MPO resulting in a 70-100% increase in proton relaxivity. As a result, we were
      able to demonstrate MPO activity in enzyme solutions and in a model tissue-like
      system. These studies suggest that activatable paramagnetic MR imaging agents can
      be used to directly image MPO activity.

PMID- 15508167
TI  - Parallel imaging performance as a function of field strength--an experimental
      investigation using electrodynamic scaling.
AB  - In this work, the dependence of parallel MRI performance on main magnetic field
      strength is experimentally investigated. Using the general framework of
      electrodynamic scaling, the B0-dependent behavior of the relevant radiofrequency
      fields at a single physical field strength of 7 T is studied. In the chosen
      implementation this is accomplished by adjusting the permittivity and
      conductivity of a homogeneous spherical phantom. With different mixing ratios of
      decane, ethanol, purified water, N-methylformamide, and sodium chloride, field
      strengths in the range of 1.5 to 11.5 T are mimicked. Based on sensitivity maps
      of an eight-coil receiver array, the field-dependent performance of parallel
      imaging is assessed in terms of the geometry factor g, which reflects noise
      enhancement in parallel imaging reconstruction. At low field strengths the SNR
      penalty was nearly independent of B0 and favorably low for 1D reduction factors
      up to between 3 and 4. At higher field strengths the transition between favorable
      and prohibitive parallel imaging conditions was found to shift toward higher
      feasible reduction factors. These findings are in good agreement with previous
      theoretical predictions. From this agreement it is concluded that parallel MRI at
      high B0 benefits specifically from onsetting far-field behavior of the involved
      radiofrequency fields.

PMID- 15508168
TI  - New modeling and experimental framework to characterize hindered and restricted
      water diffusion in brain white matter.
AB  - To characterize anisotropic water diffusion in brain white matter, a theoretical
      framework is proposed that combines hindered and restricted models of water
      diffusion (CHARMED) and an experimental methodology that embodies features of
      diffusion tensor and q-space MRI. This model contains a hindered extra-axonal
      compartment, whose diffusion properties are characterized by an effective
      diffusion tensor, and an intra-axonal compartment, whose diffusion properties are
      characterized by a restricted model of diffusion within cylinders. The hindered
      model primarily explains the Gaussian signal attenuation observed at low b
      values; the restricted non-Gaussian model does so at high b. Both high and low b
      data obtained along different directions are required to estimate various
      microstructural parameters of the composite model, such as the nerve fiber
      orientation(s), the T2-weighted extra- and intra-axonal volume fractions, and
      principal diffusivities. The proposed model provides a description of restricted
      diffusion in 3D given by a 3D probability distribution (average propagator),
      which is obtained by 3D Fourier transformation of the estimated signal
      attenuation profile. The new model is tested using synthetic phantoms and
      validated on excised spinal cord tissue. This framework shows promise in
      determining the orientations of two or more fiber compartments more precisely and
      accurately than with diffusion tensor imaging.

PMID- 15508169
TI  - Bandwidth-modulated adiabatic RF pulses for uniform selective saturation and
      inversion.
AB  - Radiofrequency (RF) inversion and saturation pulses with extremely high spatial
      selectivity and uniform profiles are a requirement for numerous MR techniques,
      such as pulsed arterial spin labeling and outer volume suppression. Adiabatic
      pulses used for inversion of longitudinal magnetization are ubiquitous, but the
      superior selectivity of adiabatic full passages has not been widely exploited for
      saturation because a simple way of calibrating the amplitude of these
      subadiabatic pulses is lacking. An analytically derived calibration equation is
      presented, applicable to a large class of pulses including the hyperbolic secant
      (HS) pulse and allowing the determination of the precise amplitude required to
      achieve any effective flip angle. The properties of this calibration are
      examined, and a highly selective and homogeneous HS saturation pulse is
      demonstrated. Based on this calibration a new class of RF pulses is developed.
      These bandwidth-modulated adiabatic selective saturation and inversion (BASSI) RF
      pulses afford optimal amplitude modulation, achieving uniform profiles at any
      effective flip angle. BASSI pulses are compared to existing gradient modulated
      adiabatic pulses in simulations and phantom experiments and shown to be superior
      in terms of selectivity and homogeneity, while requiring less RF energy. An
      application of BASSI pulses to pulsed arterial spin labeling is shown.

PMID- 15508170
TI  - Time-domain combination of MR spectroscopy data acquired using phased-array
      coils.
AB  - A new method for efficiently processing MRS data acquired with phased-array coils
      is presented. The method consists of performing phase compensation (i.e.,
      redefining the signal phase relative to a common reference) of the signals in the
      time domain prior to combining the signals. The resulting spectra are equivalent
      to those obtained by previously published methods for phased-array spectral data
      processing (i.e., processing the signals individually and then combining them in
      the frequency domain). The method allows spectra acquired with phased-array coils
      to be processed as efficiently as those acquired with non-phased-array coils.
      Both single voxel spectroscopy (SVS) and chemical shift imaging (CSI) data sets
      may be processed by this method.

PMID- 15508171
TI  - Floating table isotropic projection (FLIPR) acquisition: a time-resolved 3D
      method for extended field-of-view MRI during continuous table motion.
AB  - In this work, 3D vastly undersampled isotropic projection (VIPR) acquisition is
      used simultaneously with continuous table motion to extend the superior/inferior
      (S/I) FOV for MR angiograms. The new technique is termed floating table isotropic
      PR (FLIPR). The use of 3D PR in conjunction with table motion obviates the need
      to locate and prescribe imaging volumes containing the major blood vessels over
      the large superior-inferior (S/I) ranges encountered in whole-body imaging. In
      addition, the FLIPR technique provides extended anterior-posterior (A/P)
      abdominal coverage, isotropic spatial resolution, and temporal resolution. In
      volunteer studies, FLIPR MR angiograms with 1.6-mm isotropic spatial resolution
      that approached whole body in extent were acquired in less than 2 min.

PMID- 15508172
TI  - Calibration of echo-planar 2D-selective RF excitation pulses.
AB  - Echo-planar radiofrequency (RF) pulses (EPP) are increasingly being used for 2D
      selective excitation in MRI. Pulse schemes of this kind are susceptible to eddy
      current effects, timing imperfections, and anisotropy of the gradient system. As
      a consequence, practical EPP implementations have been restricted to robust fly
      back strategies that use only every other leg of the echo-planar trajectory for
      RF transmission. The present work is dedicated to enabling forward-backward EPP
      with RF transmission during each k-space segment, hence doubling the pulses' time
      efficiency. This is accomplished by comprehensive pulse calibration based on
      preparatory measurements of the system imperfections, including potential
      gradient anisotropy. The effectiveness of the method is demonstrated in vitro and
      in vivo. By doubling the speed of k-space coverage, the proposed method enhances
      the potential of EPP for numerous applications. For example, motion-sensitive
      techniques benefit from shorter feasible echo times (TEs) and improved excitation
      profiles resulting from reduced in-pulse motion. In sequences with fast
      repetition, shorter EPP help reduce the overall scan duration. Alternatively, the
      higher time efficiency of forward-backward EPP can enhance their spatial
      selectivity.

PMID- 15508173
TI  - Automatic spatial and temporal temperature control for MR-guided focused
      ultrasound using fast 3D MR thermometry and multispiral trajectory of the focal
      point.
AB  - Of the different modalities to induce local hyperthermia, focused ultrasound is
      the only noninvasive technology available at the moment. In addition to the 3D
      localization of the target region, it has been shown that MRI can provide real
      time thermometry and allows online, automatic control of temperature evolution of
      the focal point. Treatment of a large tissue volume (as compared to the focal
      spot size, i.e., the ultrasound wavelength) can be achieved rapidly by moving the
      focal point along an inside-out spiral trajectory. It has been shown previously
      that under linear conditions of energy deposition versus temperature, the spatial
      profile of the temperature within a large area can be controlled. In this study,
      a proportional, integral, and derivative (PID) spatial-and-temporal controller is
      described for the control of the temperature evolution within the target region
      under more variable conditions. The aim was to reach a predefined temperature
      profile after a few successive trajectories. Heat conduction in tissue is
      exploited to obtain a uniform temperature increase in a volume using discrete
      sonications without any waiting time. Input data sets consisted of 3D temperature
      maps provided online by a MR scanner. For each new trajectory, the controller
      recalculates the number of sonications per surface unit (spatial density of
      points describing the trajectory) and the applied power. Its performance was
      tested ex vivo and in vivo. Diameters of the target region ranged from 9 mm to 19
      mm. Targeted temperature increase ranged from +8 degrees C to +18 degrees C.
      Spatiotemporal temperature control showed good stability and fast convergence,
      for both circular and elliptic ROIs.

PMID- 15508174
TI  - In vivo cardiac 1H-MRS in the mouse.
AB  - The mouse is the predominant animal model to study the effect of gene
      manipulations. Imaging techniques to define functional effects on the heart
      caused by genomic alterations are becoming increasingly routine in mice, yet
      methods for in vivo investigation of metabolic phenotypes in the mouse heart are
      lacking. In this work, cardiac 1H-MRS was developed and applied in mouse hearts
      in vivo using a single-voxel technique (PRESS). In normal C57Bl/6J mice,
      stability and reproducibility achieved by dedicated cardiac and respiratory
      gating was demonstrated by measuring amplitude and zero-order phase changes of
      the unsuppressed water signal. Various cardiac metabolites, such as creatine,
      taurine, carnitine, or intramyocardial lipids were successfully detected and
      quantified relative to the total water content in voxels as small as 2 microl,
      positioned in the interventricular septum. The method was applied to a murine
      model of guanidinoacetate N-methyltransferase (GAMT) deficiency, which is
      characterized by substantially decreased myocardial creatine levels. Creatine
      deficiency was confirmed noninvasively in myocardium of anesthetized GAMT-/-
      mice. This is the first study to report the application of cardiac 1H-MRS in mice
      in vivo.

PMID- 15508175
TI  - Mutation effects of a conserved alanine (Ala510) in type I polyhydroxyalkanoate
      synthase from Ralstonia eutropha on polyester biosynthesis.
AB  - Type I polyhydroxyalkanoate (PHA) synthases, as represented by Ralstonia eutropha
      enzyme (PhaC(Re)), have narrow substrate specificity toward (R)-3-hydroxyacyl
      coenzyme A with acyl chain length of C3-C5 to yield PHA polyesters. In this
      study, saturation point mutagenesis of a highly conserved alanine at position 510
      (A510) in PhaC(Re) was carried out to investigate the effects on the
      polymerization activity and the substrate specificity for in vivo PHA
      biosynthesis in bacterial cells. A series of saturation mutants were first
      applied for poly[(R)-3-hydroxybutyrate] homopolymer synthesis in Escherichia coli
      and R. eutropha PHB(-)4 (PHA negative mutant) cells to assess the polymerization
      activity. All mutants showed quantitatively similar polymerization activities
      when R. eutropha PHB(-)4 was used for assay, whereas several mutants such as
      A510P showed low activities in E. coli. Further analysis has revealed that
      majority of mutants synthesize polyesters with higher molecular weights than the
      wild-type. In particular, substitution by acidic amino acids, A510D(E), led to
      remarkable increases in molecular weights. Subsequently, PHA copolymer synthesis
      from dodecanoate (C12 fatty acid) was examined. The copolymer compositions were
      varied depending on the mutants used. Significant increased fractions of long
      monomer units (C6 and C8) in PHA copolymers were observed for three mutants
      [A510M(Q,C)]. From these results, the mutations at this potion are beneficial to
      change the molecular weight of polyesters and the substrate specificity of
      PhaC(Re). Molecular weight distributions of PHA polymers synthesized by the wild
      type enzyme (PhaC(Re)) and its mutants.

PMID- 15508176
TI  - Allergy assessment of foods or ingredients derived from biotechnology, gene
      modified organisms, or novel foods.
AB  - The introduction of novel proteins into foods carries a risk of eliciting
      allergic reactions in individuals sensitive to the introduced protein and a risk
      of sensitizing susceptible individuals. No single predictive test exists to
      perform a hazard assessment in relation to allergenic properties of newly
      expressed proteins in gene-modified organisms (GMOs). Instead, performance of a
      weighted risk analysis based on the decision tree approach has been suggested.
      The individual steps of this analysis comprise sequence homology to known
      allergens, specific or targeted serum screens for immunoglobulin E (IgE) cross
      reactions to known allergens, digestability studies of the proteins in simulated
      gastric and/or intestinal fluids, and animal studies. These steps are discussed
      and five examples of risk evaluation of GMOs or novel foods are presented. These
      include ice-structuring protein derived from fish, microbial transglutaminase,
      GMO-soybeans, amylase and the Nangai nut.

PMID- 15508177
TI  - T lymphocytes and food allergy.
AB  - Food allergy is a hypersensitivity reaction to normally harmless substances and
      involves humoral immune responses, mediated by immunoglobulin (IgE) synthesized
      by B lymphocytes, and cellular immune responses mediated by T lymphocytes. An IgE
      mediated mechanism leads to clinical symptoms occurring immediately after food
      ingestion, e. g., "the oral allergy syndrome". For delayed reactions involving
      the gastrointestinal tract or the skin, the underlying immune mechanisms are less
      clear. In order to elucidate the cellular response to food allergens, human
      allergen-specific T cell cultures generated in vitro represent helpful tools. The
      majority of food allergen-specific CD4(+) T lymphocytes isolated from food
      allergic individuals was found to synthesize high levels of IL-4 and IL-13, two
      cytokines required for initiation of IgE synthesis. Due to selective homing
      profiles, food-specific T cells seem also to be involved in defining the target
      organ of the allergic inflammation. Recent data provide evidence that in addition
      to IgE-mediated inflammation, food allergen-specific T lymphocytes may also cause
      inflammatory responses independently of IgE-mediated mechanisms.

PMID- 15508178
TI  - Evaluation of the potential allergenicity of the enzyme microbial
      transglutaminase using the 2001 FAO/WHO Decision Tree.
AB  - All novel proteins must be assessed for their potential allergenicity before they
      are introduced into the food market. One method to achieve this is the 2001
      FAO/WHO Decision Tree recommended for evaluation of proteins from genetically
      modified organisms (GMOs). It was the aim of this study to investigate the
      allergenicity of microbial transglutaminase (m-TG) from Streptoverticillium
      mobaraense. Amino acid sequence similarity to known allergens, pepsin resistance,
      and detection of protein binding to specific serum immunoglobulin E (IgE) (RAST)
      have been evaluated as recommended by the decision tree. Allergenicity in the
      source material was thought unlikely, since no IgE-mediated allergy to any
      bacteria has been reported. m-TG is fully degraded after 5 min of pepsin
      treatment. A database search showed that the enzyme has no homology with known
      allergens, down to a match of six contiguous amino acids, which meets the
      requirements of the decision tree. However, there is a match at the five
      contiguous amino acid level to the major codfish allergen Gad c1. The potential
      cross reactivity between m-TG and Gad c1 was investigated in RAST using sera from
      25 documented cod-allergic patients and an extract of raw codfish. No binding
      between patient IgE and m-TG was observed. It can be concluded that no safety
      concerns with regard to the allergenic potential of m-TG were identified.

PMID- 15508179
TI  - Food allergy to apple and specific immunotherapy with birch pollen.
AB  - Conflicting results concerning the effect of specific pollen immunotherapy (SIT)
      on allergy to plant foods have been reported. The aim of this study was to
      investigate the effect of SIT using a birch pollen extract on food allergy with
      focus on allergy to apple. Seventy-four birch pollen-allergic patients were
      included in a double-blind, double-dummy, and placebo-controlled comparison of
      sublingual-swallow (SLIT) and subcutaneous (SCIT) administration of a birch
      pollen extract. Sixty-nine percent of these patients reported allergy to apple.
      The clinical reactivity to apple was evaluated by open oral challenges with fresh
      apple and a questionnaire. The immunoglobulin E (IgE)-reactivity was assessed by
      skin prick test (SPT), specific IgE, and leukocyte histamine release (HR). Forty
      patients were included in the final evaluation of the effect of SIT. The
      challenges were positive in 9 (SCIT), 6 (SLIT), and 8 (placebo) patients after
      treatment compared to 10, 4, and 10 patients, respectively, before SIT. The
      symptom scores to apple during challenges decreased in all groups, but only
      significantly in the placebo group (p = 0.03). As evaluated by the questionnaire,
      the severity of food allergy in general did not change and there were no
      differences between the groups. In spite of a significant effect on seasonal hay
      fever symptoms and use of medication and decrease in IgE-reactivity, SIT was not
      accompanied by a significant decrease in the severity of allergy to apple
      compared to placebo. Therefore, oral allergy syndrome (OAS) to apple should not
      be considered as a main criterion for selecting patients for birch pollen
      immunotherapy at present.

PMID- 15508180
TI  - Development of an epitope-specific analytical tool for the major peanut allergen
      Ara h 2 using a high-density multiple-antigenic peptide strategy.
AB  - Using the major peanut allergen Ara h 2 as an example, an analytical tool
      enabling the determination of immunoglobulin E (IgE)-epitopes in processed food
      allergens was developed. We synthesized a multiple-antigenic peptide (MAP) of the
      IgE-reactive linear epitope 3 (amino acid positions 27-36) of Ara h 2 and raised
      a monospecific antiserum against this epitope to obtain a positive control for
      future epitope resolved diagnostics. First, a MAP of epitope 3, having a
      molecular mass of 7770 Da, was synthesized, purified, and its structure confirmed
      by liquid chromatography-mass spectrometry (electrospray ionization) (LC
      MS(ESI)), matrix assisted laser desorption/ionization-time of flight (MALDI-TOF),
      and Edman sequencing. The MAP was then used to raise high titer antibodies in
      rabbits using the adjuvant Titermax and to characterize the specificity of IgE
      from allergenic patients sensitized to Ara h 2. The antiserum exclusively detects
      Ara h 2 in crude peanut extract with a titer of 10(7) by Western blot and reacts
      specifically with epitope 3 shown by epitope mapping for a library of solid-phase
      bound synthetic 15-mer peptides covering the entire sequence of Ara h 2. Such IgE
      reactive epitopes are of high analytical relevance as they could constitute the
      basis for epitope-specific detection systems for use in quality control in the
      food industry or for forensic purposes in cases of fatal reactions to otherwise
      undetected peanut proteins.

PMID- 15508181
TI  - Effect of roasting history and buffer composition on peanut protein extraction
      efficiency.
AB  - Peanut is a major allergenic food. Undeclared peanut (allergens) from mis
      formulation or contamination during food processing pose a potential risk for
      sensitized individuals and must be avoided. Reliable detection and quantification
      methods for food allergens are necessary in order to ensure compliance with food
      labelling and to improve consumer protection. The extraction of proteins from
      allergenic foods and complex food products is an important step in any allergen
      detection method. In this study, the protein extraction efficiency of various
      buffers prepared in-house and some extraction buffers included in some commercial
      allergen enzyme-linked immunosorbent assay (ELISA) test kits for peanut
      determination in food products were tested. In addition, the effect of roasting
      history on the extractability of peanut protein was investigated by the biuret
      and the bicinchoninic acid (BCA) assays. Elevated roasting temperatures in food
      processing were found to have a major impact on protein extraction efficiency by
      reducing protein yields of oil and dry roasted peanuts by 50-75% and 75-80%,
      respectively, compared with the raw material. Extraction buffers operating in the
      higher pH range (pH 8-11) showed best yields.

PMID- 15508184
TI  - Decreased survival of B cells of HIV-viremic patients mediated by altered
      expression of receptors of the TNF superfamily.
AB  - Human immunodeficiency virus (HIV) infection leads to numerous perturbations of B
      cells through mechanisms that remain elusive. We performed DNA microarray,
      phenotypic, and functional analyses in an effort to elucidate mechanisms of B
      cell perturbation associated with ongoing HIV replication. 42 genes were up
      regulated in B cells of HIV-viremic patients when compared with HIV-aviremic and
      HIV-negative patients, the majority of which were interferon (IFN)-stimulated or
      associated with terminal differentiation. Flow cytometry confirmed these
      increases and indicated that CD21(low) B cells, enhanced in HIV-viremic patients,
      were largely responsible for the changes. Increased expression of the tumor
      necrosis factor (TNF) superfamily (TNFSF) receptor CD95 correlated with increased
      susceptibility to CD95-mediated apoptosis of CD21(low) B cells, which, in turn,
      correlated with HIV plasma viremia. Increased expression of BCMA, a weak TNFSF
      receptor for B lymphocyte stimulator (BLyS), on CD21(low) B cells was associated
      with a concomitant reduction in the expression of the more potent BLyS receptor,
      BAFF-R, that resulted in reduced BLyS binding and BLyS-mediated survival. These
      findings demonstrate that altered expression of genes associated with IFN
      stimulation and terminal differentiation in B cells of HIV-viremic patients lead
      to an increased propensity to cell death, which may have substantial deleterious
      effects on B cell responsiveness to antigenic stimulation.

PMID- 15508185
TI  - Dilating the degradome: matrix metalloproteinase 2 (MMP-2) cuts to the heart of
      the matter.
AB  - With recent work revealing that MMPs (matrix metalloproteinases) cleave an
      increasingly large degradome of bioactive and signalling molecules, the dogma
      that MMPs are extracellular-matrix-remodelling proteases is under challenge. In
      this issue of the Biochemical Journal, Martinez et al. have reported that AM
      (adrenomedullin), a potent vasodilator predominantly expressed by blood vessel
      endothelial and smooth muscle cells, and microvasculature-rich tissues, is
      another new bioactive substrate for MMPs in vivo. Cleavage by MMP-2, but not MMP
      9, generates a series of peptides; two of which retain receptor agonist and
      vasodilator activity, three are inactive and, excitingly, AM(11-22), a small
      product containing a canonical disulphide loop, is a vasoconstrictor. In view of
      the robust vasodilatory and other cardiac protective activities of AM in
      inhibiting myocardial fibrosis this represents a potent new systemic role for MMP
      2 in the cardiovasculature. Hence, the paper by Martinez et al. directly
      implicates MMP activity in the development of hypertension and paradoxically in
      stimulating myocardial fibrosis, therefore pointing to exciting new possibilities
      for utilizing MMP-2-specific inhibitors as a new mode to treat blood pressure and
      heart disease.

PMID- 15508188
TI  - [55th Congress of the German Society of Gynecology and Obstetrics. Hamburg,
      Germany, 14-17 September 2004. Abstracts].

PMID- 15508191
TI  - Detection of tumor markers including carcinoembryonic antigen, APC, and cyclin D2
      in fine-needle aspiration fluid of breast.
AB  - CONTEXT: The traditional triple test for breast cancer diagnosis is physical
      examination, mammography, and aspiration cytology. However, the accuracy of
      mammography on young women with nonatrophied breasts is poor compared with that
      for women older than 50 years, and additional methods for diagnosis of breast
      cancer are needed. OBJECTIVE: To investigate whether carcinoembryonic antigen
      (CEA), CA 15-3, and CA 125 concentrations in breast aspiration fluid are useful
      as breast cancer biochemical markers and whether APC and cyclin D2 gene promoter
      hypermethylation could be regarded as a breast cancer molecular marker. DESIGN:
      CEA, CA 15-3, and CA 125 concentrations were measured, and methylation status of
      the APC gene promoter 1A and the promoter region of the cyclin D2 gene were
      analyzed using a methylation-specific polymerase chain reaction assay of ex vivo
      breast aspiration fluid obtained from 49 samples of excised breast tissue.
      SETTING: The specimens were collected during a 1-year period in the tertiary care
      teaching hospital in Seoul, Korea. PATIENTS: Forty-nine patients with breast
      masses were surgically treated. Thirty-four patients had breast cancer, and 15
      had benign breast disease. RESULTS: Aspiration fluid CEA concentrations were
      significantly higher in breast cancer cases than in cases of benign breast
      disease (mean, 69.90 ng/mg protein vs 0.68 ng/mg protein, respectively; P <
      .001). At 90% specificity of the assay (CEA, 2.13 ng/mg protein), the
      corresponding sensitivity for breast cancer detection was 62%, according to the
      receiver operating characteristic curve drawn. The APC gene promoter 1A and the
      promoter region of the cyclin D2 gene were methylated in 42% (14/33) and 70%
      (23/33) of the breast cancer aspiration fluid samples, respectively. A cumulative
      incidence of methylation of these 2 genes was 85% (28/33). The APC and cyclin D2
      gene promoters were both unmethylated in the aspiration fluids from 19 women with
      nonmalignant breast disease. CONCLUSIONS: Breast aspiration fluid CEA
      concentration and the methylation of the APC gene promoter 1A and the promoter
      region of the cyclin D2 gene can be used as tumor markers to overcome some of the
      limitations of aspiration cytology. In combination with the mammogram and
      physical examination, assays for these markers could be used to help determine a
      definitive diagnosis when cytologic results are suspicious for malignancy.

PMID- 15508192
TI  - Bone morphogenetic proteins are expressed by both bone-forming and non-bone
      forming lesions.
AB  - CONTEXT: Bone morphogenetic proteins (BMPs) are thought to be responsible for
      bone formation; they cause bone to form in soft tissues and are clinically used
      in helping fracture union or tumor reconstructions. Skeletal metastases from
      epithelial tumors may be either bone-forming (blastic) or non-bone-forming
      (lytic). OBJECTIVE: We studied the expression of BMPs in a variety of primary and
      secondary lesions of bone (both bone-forming and non-bone-forming) to determine
      if there was a consistent relationship between bone formation and BMP expression.
      DESIGN: We compared a bone-forming lesion (fibrous dysplasia) with a non-bone
      forming lesion (desmoid tumor), using reverse transcription-polymerase chain
      reaction, Northern blot analysis, and immunohistochemistry to detect BMPs. We
      also studied a number of non-bone-forming secondary lesions (carcinomas that
      formed lytic metastases to the skeleton) and found BMP production in most of
      these tumors. RESULTS: We found that BMPs were expressed in both bone-forming and
      non-bone-forming benign musculoskeletal lesions. In the first part of the study,
      BMPs were found in both fibrous dysplasia and desmoid tumors. Bone morphogenetic
      proteins were also expressed by several tumors. In the next part of the study
      (paraffin-embedded tissue), BMPs were expressed by a variety of tumors,
      irrespective of the radiological nature (blastic or lytic) of their metastases.
      CONCLUSIONS: We conclude that BMP production alone cannot explain bone formation,
      and other factors either alone or in combination may be responsible for blastic
      metastases to the skeleton and for bone formation by primary bone lesions, such
      as fibrous dysplasia.

PMID- 15508193
TI  - Reproductive tract infections in rural women from the highlands, jungle, and
      coastal regions of Peru.
AB  - OBJECTIVE: To define the prevalences and manifestations of reproductive tract
      infections (RTIs) in rural Peruvian women. METHODS: During 1997-98, we visited 18
      rural districts in coastal, highlands, and jungle regions of Peru. We
      administered standardized questionnaires and pelvic examinations to members of
      women's community-based organizations; and collected vaginal fluid for pH, amine
      odour, Gram stain, microscopy, and culture for Trichomonas vaginalis; cervical
      specimens for Chlamydia trachomatis, Neisseria gonorrhoeae; human papilloma virus
      (HPV) by polymerase chain reaction (PCR) assays, and blood for syphilis serology.
      FINDINGS: The 754 participants averaged 36.9 years of age and 1.7 sex partners
      ever; 77% reported symptoms indicative of RTIs; 51% and 26% reported their
      symptoms spontaneously or only with specific questioning, respectively. Symptoms
      reported spontaneously included abnormal vaginal discharge (29.3% and 22.9%,
      respectively). One or more RTIs, found in 70.4% of participants, included
      bacterial vaginosis (43.7%), trichomoniasis (16.5%), vulvovaginal candidiasis
      (4.5%), chlamydial infection (6.8%), gonorrhoea (1.2%), syphilis seropositivity
      (1.7%), cervical HPV infection (4.9%), and genital warts or ulcers (2.8%). Of 715
      adequate Pap smears, 7 revealed cancer, 4 high-grade squamous intra-epithelial
      lesions (SIL) and 15 low-grade SIL. Clinical algorithms had very low sensitivity
      and predictive values for cervical infection, but over half the women with
      symptoms of malodorous vaginal discharge, signs of abnormal vaginal discharge, or
      both, had bacterial vaginosis or trichomoniasis. CONCLUSION: Overall, 77% of
      women had symptoms indicative of RTIs, and 70% had objective evidence of one or
      more RTIs. Women with selected symptoms and signs of vaginal infection could
      benefit from standard metronidazole therapy.

PMID- 15508194
TI  - Psychometric properties of the WHO Quality of Life questionnaire (WHOQOL-100) in
      patients with chronic diseases and their caregivers in China.
AB  - OBJECTIVE: To evaluate the psychometric properties of the WHO Quality of Life
      questionnaire (WHOQOL-100), a multi-dimensional, conceptualized, 100-item quality
      of-life instrument. METHODS: A total of 460 patients in China with chronic
      diseases (including hypertension, schizophrenia, stroke, end-stage renal disease,
      head and neck cancer and breast cancer) and 418 family members who were their
      caregivers were assessed at baseline and one year later. FINDINGS: The WHOQOL-100
      had acceptable internal consistency (alpha = 0.76-0.90 across domains). There
      were strong correlations between the domains of WHOQOL-100 and the dimensions of
      the General Quality of Life Inventory (alpha = 0.72-0.82 across related domains).
      Within domains most facet correlations were satisfactory, although some facets
      correlated more strongly with a domain other than that to which they had been
      assigned. Principal component analysis produced four factors accounting for 61%
      of the total variance. CONCLUSION: The WHOQOL-100 was able to discriminate
      between the different groups of patients and was sensitive to clinical change in
      patients' conditions. It proved to be a reliable and valid instrument for
      assessing the quality of life of patients with chronic diseases and their
      caregivers in China.

PMID- 15508195
TI  - Improving antimicrobial use among health workers in first-level facilities:
      results from the multi-country evaluation of the Integrated Management of
      Childhood Illness strategy.
AB  - OBJECTIVE: The objective of this study was to assess the effect of Integrated
      Management of Childhood Illness (IMCI) case management training on the use of
      antimicrobial drugs among health-care workers treating young children at first
      level facilities. Antimicrobial drugs are an essential child-survival
      intervention. Ensuring that children younger than five who need these drugs
      receive them promptly and correctly can save their lives. Prescribing these drugs
      only when necessary and ensuring that those who receive them complete the full
      course can slow the development of antimicrobial resistance. METHODS: Data
      collected through observation-based surveys in randomly selected first-level
      health facilities in Brazil, Uganda and the United Republic of Tanzania were
      statistically analysed. The surveys were carried out as part of the multi-country
      evaluation of IMCI effectiveness, cost and impact (MCE). FINDINGS: Results from
      three MCE sites show that children receiving care from health workers trained in
      IMCI are significantly more likely to receive correct prescriptions for
      antimicrobial drugs than those receiving care from workers not trained in IMCI.
      They are also more likely to receive the first dose of the drug before leaving
      the health facility, to have their caregiver advised how to administer the drug,
      and to have caregivers who are able to describe correctly how to give the drug at
      home as they leave the health facility. CONCLUSIONS: IMCI case management
      training is an effective intervention to improve the rational use of
      antimicrobial drugs for sick children visiting first-level health facilities in
      low-income and middle-income countries.

PMID- 15508196
TI  - Wheezing conditions in early childhood: prevalence and risk factors in the city
      of Sao Paulo, Brazil.
AB  - OBJECTIVE: To investigate the prevalence and risk factors for wheezing disorders
      in early childhood in Sao Paulo, Brazil, the largest metropolitan area of South
      America. METHODS: A population-based cross-sectional survey of 1132 children aged
      6-59 months was carried out between 1995 and 1996 to obtain information on recent
      wheezing and on independent variables such as demographic, socioeconomic,
      environmental, maternal and nutritional variables and immunization status.
      Intestinal parasitic infections were diagnosed using standard techniques.
      Multiple unconditional logistic regression was used to describe associations
      between outcome and independent variables. FINDINGS: The prevalence of recent
      wheezing (one or more reported episodes in the past 12 months) was 12.5%; 93% of
      children with wheezing were also reported to have a medical diagnosis of asthma.
      Recent wheezing was associated with low per capita income, poor quality of
      housing, day-care attendance, low birth weight and infection with intestinal
      helminths. CONCLUSION: Wheezing in early childhood in Sao Paulo, although more
      common than in most developing countries, remains less prevalent than in urban
      areas of industrialized countries. Low income and conditions associated with
      poverty (poor housing, low birth weight and parasitic infections) are some of the
      main risk factors for wheezing disorders among young children in this city.

PMID- 15508197
TI  - [Recommendations of good practice: medicines that induce ovulation (April 2004)].

PMID- 15508198
TI  - Induction and detection of disturbed homeostasis in cardiopulmonary bypass.
AB  - During cardiopulmonary bypass (CPB) haemodynamic alterations, haemostasis and the
      inflammatory response are the main causes of homeostatic disruption. Even with
      CPB procedures of short duration, the homeostasis of a patient is disrupted and,
      in many cases, requires intensive postoperative treatment to re-establish the
      physiological state of the patient. Although mortality is low, disruption of
      homeostasis may contribute to increased morbidity, particularly in high-risk
      patients. Over the past decades, considerable technical improvements in CPB
      equipment have been made to prevent the development of the systemic inflammatory
      response syndrome (SIRS). Despite all these improvements, only the inflammatory
      response, to some extent, has been reduced. The microcirculation is still
      impaired, as measured by tissue degradation products of various organs,
      indicating that CPB may still be considered as an unphysiological procedure. The
      question is, therefore, whether we can detect the pathophysiological consequences
      of CPB in each individual patient with valid bedside markers, and whether we can
      relate this to determinant factors in the CPB procedure in order to assist the
      perfusionist in improving the adequacy of CPB. The use of these markers could
      play a pivotal role in decision making by providing an immediate feedback on the
      determinant quality of perfusion. Therefore, we suggest validating the proposed
      markers in a nomogram to optimize not only the CPB procedure, but also the
      patient's safety.

PMID- 15508199
TI  - Long-range rescue helicopter missions in the Arctic.
AB  - BACKGROUND: Search and rescue helicopters from the Royal Norwegian Air Force
      conduct ambulance and search and rescue missions in the Barents Sea. The team on
      board includes an anesthesiologist and a paramedic. Operations in this area are
      challenging due to long distances, severe weather conditions, and arctic winter
      darkness. METHODS: One-hundred, forty-seven ambulance and 29 search and rescue
      missions in the Barents Sea during 1994-1999 were studied retrospectively with
      special emphasis on operative conditions and medical results. RESULTS AND
      DISCUSSION: Thirty-five percent of the missions were carried out in darkness. The
      median time from the alarm to first patient contact was 3.3 hours and the median
      duration of the missions was 7.3 hours. Forty-eight percent of the missions
      involved ships of foreign origin. Half the patients had acute illnesses,
      dominated by gastrointestinal and heart diseases. Most of the injuries resulted
      from industrial accidents with open and closed fractures, amputations, and soft
      tissue damage. Ninety percent of the patients were hospitalized; 7.5% probably
      would not have survived without early medical treatment and rapid transportation
      to a hospital. CONCLUSION: Using a heavy search and rescue helicopter in the
      Barents Sea was the right decision in terms of medical gain and operative risk.

PMID- 15508202
TI  - Absence of brain antibodies in patients with schizophrenia.

PMID- 15508203
TI  - Gonadotrophin stimulation test ovarian function.

PMID- 15508204
TI  - Comparison of continuous and intermittent anorectic therapy in obesity.

PMID- 15508205
TI  - Carotid compression tonography: a new test for carotid insufficiency.

PMID- 15508206
TI  - Panhypopituitarism after cured tuberculous meningitis.

PMID- 15508207
TI  - Malignant jaundice.

PMID- 15508208
TI  - Clomiphene citrate.

PMID- 15508209
TI  - Accidents, emergencies, and ambulances: a survey in Portsmouth.

PMID- 15508210
TI  - Personal view. Heart transplantation.

PMID- 15508211
TI  - Is there a constitutional right to clone?

PMID- 15508212
TI  - What's so strange about human cloning?

PMID- 15508213
TI  - What's in a name? "Nuclear transplantation" and the ethics of stem cell research.

PMID- 15508214
TI  - Public policy crafted in response to public ignorance is bad public policy.

PMID- 15508215
TI  - Seeing double: the ethics of human cloning.

PMID- 15508216
TI  - Placing a moratorium on research cloning to ensure effective control over
      reproductive cloning.

PMID- 15508217
TI  - Human cloning: insights from twins and twin research.

PMID- 15508218
TI  - Cloning and government regulation.

PMID- 15508219
TI  - Human cloning: myths, medical benefits and constitutional rights.

PMID- 15508220
TI  - Cloning, science and public policy.

PMID- 15508221
TI  - Cloning and commodification.

PMID- 15508222
TI  - Cloning and federalism.

PMID- 15508224
TI  - Completing life and dying triumphantly.

PMID- 15508225
TI  - Mandatory newborn HIV testing.

PMID- 15508226
TI  - Genetic interventions: (yet) another challenge to allocating health care.

PMID- 15508227
TI  - Genetic enhancement, distributive justice, and the goals of medicine.

PMID- 15508228
TI  - Punishing reproductive choices in the name of liberal genetics.

PMID- 15508229
TI  - How not to end disability.

PMID- 15508230
TI  - Is moral theory perplexed by new genetic technology?

PMID- 15508231
TI  - The ethics of genetic intervention: human research and blurred species
      boundaries.

PMID- 15508232
TI  - A Rawlsian approach to solving the problem of genetic discrimination in toxic
      workplaces.

PMID- 15508233
TI  - Does technological enhancement of human traits threaten human equality and
      democracy?

PMID- 15508234
TI  - Retraction of "Biotransformation of drugs by microbial cultures for predicting
      mammalian drug metabolism" [Biotechnol. Adv. 21 (2003) 3-39].

PMID- 15508235
TI  - Public information policy revised to delete reference to standards areas in
      Quality Report.

PMID- 15508236
TI  - Enough to make you sick.

PMID- 15508237
TI  - Off centre. Whole systems approach is a driver of change in prompting a new
      direction of travel in impenetrable NHS jargon.

PMID- 15508238
TI  - [Pharyngeal gonococcal infections].

PMID- 15508239
TI  - LD and delinquency: rethinking the "link".
AB  - Longitudinal data from a 7-year prospective study was examined to investigate
      whether the presence of learning disabilities (LD) increases a youth's risk of
      becoming a juvenile delinquent. The sample included 515 students enrolled in the
      fifth grade in the fall of 1985, 51 (9.9%) of whom were youth with LD. Self
      report data on delinquent activity were collected in the spring of 1993. Official
      court records were obtained for the years 1985 through 1992. Hierarchical
      multiple regression analyses were performed using a block of three demographic
      variables (gender, ethnicity, and socioeconomic status) as predictors in the
      first step and including LD status in a second step. Seven separate analyses were
      performed, using different measures of delinquency as criterion variables. In no
      case did LD status account for a significant portion of unique variance in the
      delinquency variables when the demographic variables were controlled for. The
      results of this study did not confirm the presence of a direct relationship
      between LD and delinquency and suggest that the finding of a direct relationship
      in other studies may have been due to confounding of the LD status with age,
      ethnicity, or socioeconomic status.

PMID- 15508240
TI  - Social persistence following failure in boys and girls with LD.
AB  - The response of boys and girls with or without learning disabilities to social
      failure was examined. Children participated in two dyadic interactions with
      experimental confederates: an unfriendly interaction and a friendly one. The
      children's behavior was videotaped, and they answered questions following each
      interaction. The children with learning disabilities were found to be
      hyperresponsive to both interactions: They felt significantly worse following the
      unfriendly one and significantly better following the friendly interaction.
      Limited evidence was found to suggest that girls with learning disabilities were
      more adversely affected by the unfriendly interaction. Several of the findings
      were consistent with the hypothesis that children with learning disabilities show
      a learned helplessness response to social failure. The implications of these
      findings for understanding the social behavior of children with learning
      disabilities are discussed.

PMID- 15508241
TI  - Verbal retelling abilities in adolescents with and without language-learning
      disabilities for social studies lectures.
AB  - Verbal retelling abilities for social studies lectures were examined and compared
      in 20 adolescent boys, ages 12-5 to 14-7, with language-learning disabilities
      (LLD) and 29 with normal language abilities (NL). Participants viewed one
      videotaped social studies lecture with a comparison expository discourse
      structure and one with a causation discourse structure. Following each lecture
      presentation, participants verbally retold the lecture. Results of several
      repeated-measures analyses of variance indicated that the group with LLD produced
      a significantly smaller number of T-units, subordinate clauses, subordinate
      clauses per T-unit, T-units per second, lecture components per second, and
      percentage of lecture components in their retellings, compared with the group
      with NL, regardless of lecture type. Both groups produced a significantly greater
      number of T-units and subordinate clauses for the comparison lecture. By
      contrast, both groups recalled a significantly greater number of lecture
      components per T-unit and per second for the causation lecture. Results indicated
      that the comparison discourse structure facilitated more substantive and
      elaborate retellings, whereas the causation discourse structure facilitated more
      efficient, concise retellings in both groups. Research and instructional
      implications are discussed.

PMID- 15508242
TI  - Phonological and morphological processing in adult students with learning/reading
      disabilities.
AB  - A target group of college students with learning/reading disabilities was
      compared with reading-level (RA) and chronological-age (CA) contrast groups on
      several phonological and morphological computerized information-processing tasks.
      Results confirm the importance of accurate and rapid processing of simple lexical
      items to the automatic level. The target students were less accurate and took
      longer reaction time, as compared with their CA controls, though not with the RA
      contrast group, in deciding if pseudohomophonics sounded like real words and if
      pairs of words with different rime conditions rhymed. The target students showed
      both quantitative and qualitative differences in processing morphological words
      and morphographic letter strings, in contrast to some earlier findings. The
      integration of phonological and morphological knowledge is emphasized in working
      with adult college students with learning/reading disabilities.

PMID- 15508243
TI  - Arithmetic disabilities and ADD subtypes: implications for DSM-IV.
AB  - This study investigated whether specific academic deficits were associated with
      attention-deficit disorder (ADD) subtypes. Twenty students (ages 8-12) with
      attention-deficit disorder with hyperactivity (ADD/H) were compared to 20
      students with attention-deficit disorder without hyperactivity (ADD/noH). Group
      differences were compared using a MANCOVA, and paired t tests were used to
      compare within-group differences. Dependent variables for the within-group
      differences were four achievement subtest scores from the Woodcock-Johnson Psycho
      Educational Battery-Revised: Letter-Word Identification, Passage Comprehension,
      Calculation, and Applied Problems. Consistent with much of the previous research,
      no significant between-group differences were found on the achievement measures.
      Significant differences did, however, appear in the six within-group comparisons,
      all involving lower performance on the Math Calculations subtest. For students
      with ADD/H, only one comparison (with Math Applied Problems) reached
      significance. Students with ADD/noH, however, had significantly lower scores on
      the Calculation subtest compared to all of the other achievement subtests. These
      results provided additional support for the hypothesis that inattention exerts a
      specific and deleterious effect on the acquisition of arithmetic computation
      skills. These findings have important implications for the diagnosis and
      treatment of ADHD as conceptualized in the fourth edition of the Diagnostic and
      Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association,
      1994), because they suggest that students with ADHD-Predominantly Inattentive
      Type may be at increased risk for arithmetic calculation deficits.

PMID- 15508244
TI  - LD, interpersonal understanding, and social behavior in the classroom.
AB  - This study used Baron and Kenny's (1986) criteria for mediation to investigate
      the extent to which interpersonal understanding mediates the relation between
      learning disabilities (LD) and social adaptation in the classroom. Twenty-two
      children with and 22 children without a diagnosis of LD completed a
      semistructured developmental clinical interview measure of interpersonal
      understanding. They were also rated by their fourth- and fifth-grade teachers on
      a measure of social adaptation in the classroom. Interpersonal understanding and
      social adaptation in the classroom were found to be positively correlated.
      Children with LD exhibited less interpersonal understanding and social
      adaptation. Although this group difference on social adaptation was greatly
      reduced when interpersonal understanding was statistically controlled, it
      remained statistically significant. These results suggest that reduced social
      adaptation in the classroom and lower interpersonal understanding are both
      associated with a diagnosis of LD. However, they do not conclusively support the
      claim that interpersonal understanding mediates the relation between LD and
      social adaptation. Thus, whether the social difficulties of people with LD stem
      from the same complex phenomena that produce these people's learning problems
      remains an open question.

PMID- 15508245
TI  - Visual and auditory temporal processing, cross-modal transfer, and reading.
AB  - The present study reexamined the relevance of auditory and visual cross-modal
      matching to reading ability, an issue first addressed in a seminal study by Birch
      and Belmont (1964). By presenting all patterns to be matched as temporal
      sequences of tones and lights, including intramodal as well as cross-modal
      conditions, and covarying memory, three problems with the Birch and Belmont
      design were corrected. Results showed that poor readers had difficulty in
      perceiving temporal patterns generally: They did worse than good readers not only
      on cross-modal conditions but also on intramodal ones. These results were
      replicated in two tasks. Nonetheless, hierarchical regressions provided some
      indication that cross-modal abilities themselves are relevant to reading. For one
      of the two tasks, cross-modal performance contributed to the prediction of
      reading ability over and above intramodal performance. Poor readers also showed
      slower response times--a factor that contributed marginally to the prediction of
      reading independent of temporal processing.

PMID- 15508246
TI  - A Spanish perspective on LD.
AB  - This article offers an overview of special education in Spain, specifically in
      the area of learning disabilities (LD). The term LD in Spain implies a different
      conception of the definition that enjoys considerable international agreement and
      consensus. We give a historical perspective of Spanish legislation and place the
      proposed definition of LD in the context of recent school reform in Spain. The
      support services model and the assessment practices and instructional approaches
      in the LD field are described. Finally, some educational implications of the new
      school reform regarding teacher training programs to assist special educational
      needs are presented.

PMID- 15508247
TI  - [A preliminary study of biochemistry of patients with crystalline retinopathy].
AB  - PURPOSE: To investigate the pathogenesis and biochemical changes of crystalline
      retinopathy by detecting and analyzing the levels of trace elements (Cu++ and
      Zn++), blood-lipids and free amino acids in the serum of patients. METHODS: Blood
      samples of 10 patients with crystalline retinopathy and 30 normal subjects were
      collected. The levels of serum Cu++ and Zn++ were detected by using flame atomic
      absorption spectrometry, while cholesterol and triglyceride were detected by
      direct colordeveloping process and acetyl-acetone developing process respectively
      and serum amino acids by the Beckman amino acid analyzer. RESULTS: In comparison
      with the normal control group, the level of Zinc in serum was much decreased in
      the crystalline retinopathy group, while Cu++/Zn++ ratio and total cholesterol
      level in serum were significantly increased. In 3 out of 4 patients the level of
      taurine is lower than that of control group. CONCLUSION: The decrease of serum
      trace elements and taurine and the increase of cholesterol may be one of the
      important factors for the pathological changes of crystalline retinopathy. The
      administration of trace elements e. g. Zn++ and taurine might be a new therapy
      for the patients.

PMID- 15508248
TI  - [Observation of the invasion of retinoblastoma cells to ocular tissues in vitro].
AB  - PURPOSE: To study the invasion of retinoblastoma cells to ocular tissues.
      METHODS: The SO-Rb50 cells of retinoblastoma and various ocular tissue cells were
      co-cultured. The morphological change of the SO-Rb50 cells adherent to ocular
      tissue cells was observed. RESULTS: SO-Rb50 cells can adhere to the various
      ocular tissues. The adherent ability of SO-Rb50 cell to different ocular tissue
      cells was different. Tumor cells could be adhesive to keratocyte, scleral
      fibrocyte, the fibrocyte and the melanocyte of iris and choroid, the epithelial
      cells of lens, and the astrocyte of optic nerve and grow, but can not be adhesive
      to the corneal epithelial cell and retinal pigment epithelial cell. CONCLUSIONS:
      We consider that the interactions of tumor cells with host cells, as with
      extracellular matrix, also play an important role in the selective growth of
      organ and tissue of tumor cell metastasis. Retinoblastoma cells can not adhere to
      retinal pigment epithelial cell, which may serve as a barrier to obstruct the
      invasion of tumor cell to the choroid. Being adherent to the glial cells of optic
      nerve, tumor cells grow in flat and the shape of tumor cell changes, which may be
      the cause of tumor cell migrate rapidly and grow in the brain while the optic
      nerve was invaded by tumor cells.

PMID- 15508249
TI  - [Lectin-binding histochemical study on developing corneal epithelium and stroma
      of normal human being].
AB  - PURPOSE: To study glycoconjugates in developing cornea of normal human. METHODS:
      Lectin-binding histochemical method with five biotin-coupled lectins (conA, LCA,
      PNA, WGA, RCA). RESULTS: 1. WGA mainly stained the membrane of epithelial cells,
      especially in surface cells. It also stained anterior stroma of embryo. 2. All
      the layers of epithelium could be stained by conA, uneven stain was seen in
      stroma of embryo corneas. 3. RCA, LCA receptor distributed in base of cornea
      epithelium. 4. PNA can only stain cornea epithelium of 16 embryo. CONCLUSIONS: 1.
      Glycoconjugates of binding conA, WGA, PNA, LCA, RCA are in the developing corneas
      of human. 2. The distribution of these lectin receptors may change with corneal
      developing. It may be related to the maturity of corneas.

PMID- 15508250
TI  - [Relationship between glaucoma and quality of life].
AB  - PURPOSE: Assessment of the relationship between visual impairment of glaucoma and
      quality of life, and to explore the factors which affect quality of life of
      patients with glaucoma. METHODS: Sixty patients with chronic angle close glaucoma
      and open angle glaucoma were measured by the scale of quality of life for
      diseases with visual impairment. RESULTS: Scores of quality of life were
      significantly associated with visual function of glaucoma (r = 0.66, P = 0.000),
      the factors which affect quality of life were visual impairment, sex and
      occupation. CONCLUSION: The visual impairment of glaucoma may decline quality of
      life of patient. Evaluation of quality of life of patient. Evaluation of quality
      of life affords a new index for choosing strategies of glaucoma screening and
      therapies.

PMID- 15508251
TI  - [Clinical observation of the pathological changes of axial length, corneal
      curvature and posterior segment wall of eyeball in eyes with high myopia].
AB  - PURPOSE: To study the correlation between the characteristics of the morphologic
      changes in the wall of eyeball with high myopia and the visual function. METHODS:
      The axial length, corneal curvature, etc., of 280 eyes in 140 cases (the diopter
      was from -6.25D to approximately -30.00D) were examined and the data were settled
      statistically. RESULTS: (1) The corrected visual acuity in the patents with high
      myopia decreased apparently with the increase of diopter. The difference was
      significant (P < 0.001). (2) The axial length of anteroposterior diameter in
      96.1% eyes increased, with which the diopter also increased. (3) 27.1%
      exophthalmos were forward. (4) There was no significant difference when compared
      the anterior surface corneal curvature with emmetropic eyes. (5) Posterior
      scleral staphyloma occurred in 80.7% eyes. (6) Optic nerve atrophy and optic disk
      atrophic arc spot occurred in 82.3% eyes. (7) The intraocular pressure increases
      in 5.3% eyes. CONCLUSION: The severe damage to the visual function because of the
      pathological changes on the wall of eyeball is the main cause that vision can not
      be corrected in clinics.

PMID- 15508252
TI  - [A clinical analysis of 30 cases of sympathetic ophthalmia].
AB  - PURPOSE: To study the clinical characteristics of 30 patients with sympathetic
      ophthalmia in order to find out the valuable clues for future investigation.
      METHODS: The incidence, cause, location of injury, and prognosis of the 30
      patients were analyzed retrospectively. RESULTS: Patients with sympathetic
      ophthalmia occupied 0.72% of the in-patients with eye trauma in our hospital
      between 1982 and 1997. In most cases the disease related with perforating injury
      at the limbus or the sclera, but in a few cases it may be associated with blunt
      trauma, tumors or even intraocular operation. Diffuse uveitis in sympathizing eye
      happened in 63.3% of the patients. CONCLUSION: Development of sympathetic
      ophthalmia always related to the damaged ocular structure. Association of
      sympathetic ophthalmia with hereditary background and the melanin-protein may be
      worthy of study in future.

PMID- 15508253
TI  - [The diagnoses and treatment of traumatic retinal detachment].
AB  - PURPOSE: The diagnoses and treatments of traumatic retinal detachment (RD) were
      studied retrospectively in this article. METHODS: A sequence of 25 eyes of
      traumatic RD included 12 eyes of contusion, 4 explosion and 9 perforation; PVR
      (Proliferative vitreoretinopathy) < or = C grade 16 eyes and D grade 9 eyes. The
      techniques were, one: scleral cryotherapy, silicon band buckling and circling,
      external drainage, which was mainly used to PVR < or = C cases; two: vitrectomy
      and silicon oil tamponade, which was mainly used to the cases of perforated PVR-D
      cases. RESULTS: Retinal reattachment rate was 91.67% in technique one and 69.23%
      in technique two. Improvement of visual acuity showed that partial RD was better
      than total RD (P < 0.01), PVR < or = C better than PVR-D (P < 0.05) and non
      perforated better than perforated (P < 0.05). CONCLUSION: The patient who had a
      history and visual symptoms after an eye injury must be carefully examined by
      dilating pupil in order that the RD could be early inquired and treated. The
      techniques one and two must be performed in the severe perforated cases.

PMID- 15508254
TI  - [Management of anterior vitreous by high gluey Healon].
AB  - PURPOSE: To investigate the technique of managing anterior vitreous by high gluey
      Healon. METHODS: In 15 eyes of 15 cases having undertaken in situ
      phacoemulsification vitreous loss, 12 eyes of 12 cases in ECCE, 3 eyes of 2 cases
      in Marfan Syndrome, 13 eyes of 13 cases in eye injury, tunnel incision was made
      and PC-IOL implantation was performed after high gluey Healon managing anterior
      vitreous on all the cases. RESULTS: High gluey Healon managing anterior vitreous
      in 43 eyes, post capsule injuries was not enlarge, and cortex or fragments of len
      nuclear not fall in vitreous cavity. Visual acuity of 0.5 or better at
      postoperative one week were 72.1% and 59.1% respectively. CONCLUSION: The
      technique of managing anterior vitreous by high gluey Healon was worthy to be
      spread due to minimum injury, vitreous loss, and fast restoration of visual
      acuity.

PMID- 15508255
TI  - [Photocoagulation and scleral cryotherapy for Coat's disease].
AB  - PURPOSE: To evaluate the results and significance of Coat's disease with argon
      laser photocoagulation and cryotherapy. METHODS: 22 patients (23 eyes) were
      treated by argon laser (German Opton Meditek 40 E, 0.2w power, 100-500 um spot,
      0.1-0.2 second exposure and grade II reaction) and or scleral cryotherapy (-60 to
      approximately -80 degrees C, 5 second duration per time, repeating treatment if
      necessary until pale edema was seen in retina). RESULTS: 18 eyes in all (78.2%)
      had good results with visual acuity improvement and the lesion of fundus had been
      seen decreased in varient degrees. The follow-up ranged from 1 to 3 years.
      CONCLUSION: Photocoagulation and scleral cryotherapy are effective for those
      patients with Coat's disease. It is very important to treat them promptly so as
      to prevent the damage of visual function progressively.

PMID- 15508256
TI  - [Retinal vein occlusion with retinal arteriovenous communications].

PMID- 15508257
TI  - [The protection and repairment of the optic nerve injury].

PMID- 15508258
TI  - [The application of Ultrasound Biomicroscope in anterior segment contusion].
AB  - PURPOSE: To study the clinical value of Ultrasound Biomicroscope in anterior
      segment contusion. METHODS: Seven eyes with anterior segment contusion were
      examined by regular ophthalmic examination, ophthalmic B-scan, and Ultrasound
      Biomicroscope. RESULTS: Ultrasound Biomicroscope can show angle recession,
      cyclodialysis, iridodialysis, zonular breaking, lens dislocation and vitreous
      protrusion to posterior chamber. In most cases cyclodialysis and shallow
      detachment of choroid can not be diagnosed because shallow anterior chamber and
      hypton. CONCLUSION: The result suggests that Ultrasound Biomicroscope has high
      clinical value in diagnosis of anterior segment contusion, especially in cornea
      edema, hyphemia, hypton, Ultrasound Biomicroscope can refer precise diagnosis of
      anterior segment contusion.

PMID- 15508259
TI  - [Dacryocystorhinostomy for chronic dacryocystitis].

PMID- 15508260
TI  - [Dislocation of intraocular lens inferior loop and ciliochoroidal detachment
      caused by blunt contusion: a report of two cases].

PMID- 15508261
TI  - "Severe myoclonic epilepsy in infancy". Relevance for the clinician of severe
      epilepsy starting in infancy.
AB  - 'Severe myoclonic epilepsy in infancy' or Dravet syndrome is a clear example of
      the impact of severe epilepsy on the developing child. Presenting with febrile
      seizures in infancy, children later on develop a severe epileptic syndrome with
      mental retardation. Nearly all children have life-threatening status epilepticus
      during the first two years of life. The clinical diagnosis can now be confirmed
      by DNA-analysis in a majority of patients. Most patients have a de novo mutation
      in the alfa subunit of the neuronal sodium channel SCN1A. In the past few years'
      treatment of severe myoclonic epilepsy in infancy has changed. Prevention of
      seizures, avoiding anti-epileptic drugs which only block sodium channels, a
      simple combination of two major anti-epileptic drugs (sodium valproate and
      topiramate) and a strict acute seizure treatment significantly improve the
      quality of life for these patients. Long-term follow up is necessary to evaluate
      if we can also improve the development possibilities for these children.

PMID- 15508262
TI  - Correlation of clinical, MRI and Tc-99m HMPAO SPECT findings in neuro-Behcet's
      disease.
AB  - Behcet's disease (BD) is a systemic disorder of unknown cause. In our study, we
      investigated the utility of Tc-99m HMPAO SPECT and MRI in patients with neuro
      Beh,cet's disease (n-BD). PATIENTS AND METHODS: Twelve patients (two females, ten
      males; mean age 33 +/- 9.6 yr; age range 18-45 yr) with n-BD, fulfilling the
      criteria of the International Study Group for BD, were included in the study. MRI
      was performed according to a standard protocol with 1 or 1.5 T imagers. Brain
      SPECT data were obtained using a single head gamma camera after 555 MBq Tc-99m
      HMPAO injections. Following image reconstruction, regional cerebral perfusion was
      evaluated both visually and semi quantitatively. RESULTS: Neurological
      examination showed parenchymal brain involvement in 6 of 12 patients (50%). All 6
      patients had white matter lesions on MRI, while only 5 of them showed perfusion
      defects on brain SPECT. Out of 6 patients (50%) without clinical signs of
      parenchymal brain involvement, 1 patient showed a pathological brain SPECT and 3
      patients showed pathological MRI findings. Semiquantitative analysis of brain
      regions on SPECT study showed statistically significant hypoperfusion of
      biparietal regions. CONCLUSION: This study investigates the correlation between
      clinical, MRI and SPECT findings and it shows discrepancy between these findings
      in some cases. Brain SPECT may act as a complementary modality to increase the
      detection rate of affected regions in patients with n-BD.

PMID- 15508263
TI  - Comparison of vitamins K1, K2 and K3 effects on growth of rat glioma and human
      glioblastoma multiforme cells in vitro.
AB  - Glioblastoma multiforme is characterized as highly invasive and rapidly growing
      astrocytomas, and scientists have sought for efficient treatment against
      malignant gliomas for a long time. Therefore, we compared the respond of rat
      glioma (C6) and glioblastoma multiforme cells derived from two patients to
      vitamins K1, K2 and K3. The cells were exposed to 100, 250, 500, 750 and 1000
      microM of vitamins K1 and K2, and 1, 10, 25, 50, 75 and 100 microM of vitamin K3
      for 24 hours in an incubator atmosphere of 5% CO2, 37 degrees C and 100%
      humidity. Cell viability was estimated by MTT assay. Vitamin K1 showed no growth
      effect on all the glioma cells examined. Vitamin K2 did not cause any change in
      number of C6, however induced growth inhibition in a dose-dependent manner on
      glioblastoma multiforme. The IC50 values of vitamin K2 were 960 microM and 970
      microM for glioblastoma multiforme, respectively. Vitamin K3 had also growth
      inhibitory effect in a dose-dependent manner on both C6 and glioblastoma
      multiforme. The IC50 values were 41 microM, 24 microM and 23 microM for vitamin
      K3, respectively. We concluded that vitamin K3 is more effective than vitamin K2
      for inhibition of cancer cell growth, and might have an alternative value as an
      anticancer drug against glioblastoma multiforme.

PMID- 15508264
TI  - Brown-Vialetto-van Laere syndrome; the first Turkish case.
AB  - We describe a 14-year-old female patient with progressive ponto-bulbar palsy and
      deafness. The first symptom was present at the age of 9 as a difficulty in
      walking and then she was stable with mild clumsy walking till 14 year-old. It was
      noticed that she had rapidly progression gait disorder, hearing loss, difficulty
      in swallowing and speaking in a period of 2.5 months. Clinically, there were
      bilateral facial weaknesss, atrophic tongue with fasciculations, poor gag reflex,
      deafness, axial and appendicular hypotonia, severe muscular weakness involving
      muscles of neck, shoulder, and upper arms, hands with thenar and hypothenar
      amyotrophy. Hearing loss was documented by brainstem auditory evoked potentials.
      Other laboratory investigations, screening tests and imaging studing were normal.
      These clinical features are consistent with the Brown-Vialetto-van Laere
      syndrome.

PMID- 15508265
TI  - Severe peripheral polyneuropathy in a child with infective endocarditis caused by
      Staphylococcus aureus.
AB  - Although central nervous system complications such as stroke, encephalopathy and
      meningitis are commonly described in Staphylococcus aureus endocarditis,
      peripheral nervous system involvement is rarely reported in the literature. In
      this article we report on a 13-year-old boy with infective endocarditis caused by
      Staphylococcus aureus in whom severe polyneuropathy developed during
      hospitalization. To the best of our knowledge this is the first child case with
      infective endocarditis associated with peripheral polyneuropathy in the
      literature.

PMID- 15508266
TI  - Diabetic ketoacidosis presenting as a cerebral venous sinus thrombosis.
AB  - Cerebral venous sinus thrombosis is an uncommon condition with a variable
      clinical presentation, often resulting in a delayed diagnosis. The most common
      risk factors are pregnancy and puerperium, oral contraceptive use, head injury,
      dehydration, blood dyscrasias, malignancies, and systemic diseases. We present a
      nineteen-year-old female in whom a superior sagittal sinus thrombosis was caused
      by dehydration during diabetic ketoacidosis and led to the diagnosis of new-onset
      type 1 diabetes mellitus. To our knowledge this is the first published report of
      a cerebral venous sinus thrombosis in association with diabetic ketoacidosis in
      an adult.

PMID- 15508267
TI  - Calcium signal communication between glial and vascular brain cells.
AB  - The brain is composed of neurons that communicate electrical signals over
      neurites and chemical signals across synapses, and non-neuronal cells like glial
      and vascular cells that communicate calcium signals among each other Calcium ions
      have an important signaling function in the cytoplasm that depends on their
      amplitude, time course of change and subcellular localisation. Work over the last
      decade has added an additional dimension to this rich repertoire by including the
      possibility that calcium signals can be communicated between cells. In astrocytes
      and endothelial cells, connexins appear to be at the crossroad of calcium signal
      communication pathways, because they are the building blocks of gap junction
      channels that functionally connect cells, and because they can arrange as
      hemichannels that act as a conduit for cellular ATP release, thus initiating
      paracrine purinergic signaling. The two pathways appear to be operational in
      astrocytes and endothelial cells and we review in this paper possible functions
      of astrocyte-to-blood vessel calcium signaling at the level of arterioles where
      blood flow is controlled, at the level of capillaries where the blood-brain
      barrier is located and at the level of blood immune cells.

PMID- 15508268
TI  - Paraneoplastic limbic encephalitis: diagnostic relevance of CSF analysis and
      total body PET scanning.
AB  - We report two cases of paraneoplastic limbic encephalitis (PLE) that differed in
      their clinical patterns, the underlying tumours, and the associated
      paraneoplastic antibodies. The first patient was a young adult male, with anti-MA
      2 antibodies and testicular tumour. The clinical picture was restricted to limbic
      involvement. The second patient was a 56-year old, female heavy smoker; with
      seizures and depression, but also vertigo and diplopia. A low level of serum anti
      Hu antibodies led to the detection of a small cell lung carcinoma by total body
      PET-scanning. In both cases, intrathecal synthesis of CSF oligoclonal IgG bands
      and of the corresponding paraneoplastic antibodies was demonstrated.

PMID- 15508269
TI  - Prolonged hyperglycemia in the early subacute period after cerebral infarction:
      effects on short term prognosis.
AB  - Although the adverse effect of admission hyperglycemia in cerebral infarction on
      prognosis is well known, studies generally have not questioned the effect of
      hyperglycemia in the early subacute period on prognosis after a stroke. Forty-six
      patients with acute ischemic stroke were seperated into 3 groups: Group 1) Known
      diabetes or admission blood glucose (ABG) > or = 140 mg/dl and HbA1c > or =
      8,0%); Group 2) ABG > or = 140 mg/dl and HbA1c < 8,0%; and Group 3) ABG < 140
      mg/dl and HbA1c < 8,0%. Blood glucose was followed-up 4 times a day for 10 days
      after the stroke and the mean of these measurements was calculated as the mean of
      glycemic regulation (MGR). Neurological evaluation was done at presentation and
      on day 10 and 30 with the National Institute of Health (NIH) scale. Oedema,
      lesion size and presence of hemorrhagic transformation were evaluated using CT.
      The MGR was significantly higher in group 1 compared to the other two groups (p <
      0,001 and p < 0,01) and in group 2 compared to group 3 (p < 0,001). Patients with
      clinical worsening had a significantly higher MGR (p < 0,05). Patients with
      marked cerebral edema had a significantly higher MGR (p < 0,01) compared to
      patients with lesser edema. No correlation was found between MGR and lesion size
      or hemorrhagic transformation. Our results show that hyperglycemia in the early
      subacute period after cerebral infarction is associated with more pronounced
      cerebral edema and has an adverse effect on short term prognosis. We suggest that
      studies investigating the effect of insulin infusion on stroke prognosis should
      also consider infusions for a longer period than 24 hours.

PMID- 15508270
TI  - Epilepsy and driving in Belgium: proposals and justification.
AB  - Proposals about the regulations and medical criteria concerning epilepsy and
      driving, originally drawn up by the Commission on Epilepsy and Risk from the
      Belgian League against Epilepsy were discussed and amended by a panel of
      representatives of several scientific societies and of all Belgian universities
      in order to establish a broad consensus among Belgian epileptologists. The
      history of driving licencing in Belgium is discussed and some background
      information given to put the regulations in perspective. A proposal is made for
      an acceptable level of risk. Subsequently, a quantification of risk for different
      situations concerning seizures is attempted. The proposals will be discussed and
      some further practical advice given. Individual assessment of the ability to
      drive remains indispensable.

PMID- 15508271
TI  - Subacute Hashimoto's encephalopathy, treated with plasmapheresis.
AB  - We report a patient with subacute diffuse encephalopathy characterised by rapidly
      progressive dementia with visual hallucinations, myoclonus and generalised
      seizures. She was euthyroid but showed high serum levels of thyreoglobulin and
      thyreoperoxidase antibodies. Hashimoto's encephalopathy was diagnosed. MRI of the
      brain in the acute phase demonstrated no structural abnormalities. However in the
      mesotemporal regions and the anterior parts of the brain, a decrease of the N
      acetylaspartate and an increase of the Choline-containing compounds was found on
      MRI-spectroscopy. Reversal of these abnormalities was demonstrated a few months
      later after starting therapy. Plasmapheresis resulted in normalisation of serum
      levels of the antibodies and rapid clinical improvement. This observation
      supports the idea that a correlation exists between the serum levels of the
      thyroid auto-antibodies and the course of the clinical illness.

PMID- 15508272
TI  - Subclinical celiac disease with cerebellar ataxia.
AB  - We report an unusual case of celiac disease with cerebellar ataxia.
      Gastrointestinal signs and malabsorption were not found in this patient. We
      suggested that celiac disease should be taken into consideration in differential
      diagnosis of patients with cerebellar ataxia with unknown etiology.

PMID- 15508273
TI  - Active myogenic tone: a requisite for hemoglobin mediated vascular contraction?
AB  - Acellular free hemoglobin (Hb), when intravenously administered to animals and
      humans, elicits vascular contraction. A primary mechanism for the Hb mediated
      vasoconstriction is Hb scavenging of nitric oxide (NO), a potent relaxation
      factor, constitutively secreted by the vascular endothelium. However, in the
      isolated rat thoracic aorta in basal state, Hb does not elicit contraction. To
      investigate this apparent paradox, we assessed isolated rat aortic ring isometric
      contraction responses to Hb under different myogenic tone states: (1) following
      equilibration at a submaximal tension, (2) following agonist induced contraction,
      or (3) following a passive mechanical stretch. In vessel rings at basal state, Hb
      as high as 4 microM did not elicit any measurable contractions. In contrast, in
      vessel rings tone enhanced with norepinephrine, Hb as low as 0.1 microM Hb
      elicited a significant additional contraction. In vessel rings with passively
      induced tone, 4 microM Hb did not elicit a notable contraction. Similarly, in
      vessel rings in basal state, 0.17-1 mM acetylcholine, a NO dependent vasodilator,
      did not elicit relaxation. In these vessel rings, exogenous 8-Br-cGMP, a membrane
      permeable cGMP analog, did not elicit relaxation. In conclusion, in the isolated
      rat thoracic aorta, Hb mediated contraction may be contingent upon the state of
      myogenic tone.

PMID- 15508274
TI  - Review of hemoglobin-induced myocardial lesions.
AB  - Over 100 preclinical studies in several small and large animal species were
      performed to evaluate the safety and efficacy of diaspirin cross-linked
      hemoglobin (DCLHb; Baxter Healthcare Corp.) as an oxygen therapeutic. During the
      preclinical evaluation of DCLHb, myocardial lesions were observed following the
      administration of DCLHb to certain species. These lesions were characterized as
      minimal to moderate, focal-to-multifocal myocardial degeneration and/or necrosis
      that were scored using a severity scale of minimal to marked in relative
      severity. The lesions were typically observed 24-48 h after single topload
      infusions of DCLHb into rhesus monkeys or pigs at doses as low as 200 or 700
      mg/kg, respectively. Dogs, sheep, and rats did not develop these lesions after
      single-dose administrations of DCLHb. The left ventricular myocardium, typically
      near the base of or including the papillary muscles, was the most severely
      affected region, followed by the intraventricular septum and the right ventricle.
      The left and right atria were usually not affected. In a study in rhesus monkeys,
      morphometric analysis revealed that these lesions comprised less than 3% of the
      total myocardium. Although increases in serum enzyme activities (AST, CK, LDH)
      were observed after infusion of DCLHb, myocardial-related isoenzymes did not
      increase. ECG analysis and echocardiography were not altered by these lesions,
      and there was no observable adverse effect on myocardial function. Polymerization
      of DCLHb reduced, but did not eliminate, the incidence and severity of the
      lesions. However, infusion of hemoglobin solutions with reduced reaction rates
      with nitric oxide (NO) resulted in a significant decrease in lesion incidence and
      severity, while administration of L-NAME, an NO synthase inhibitor, resulted in
      the appearance of lesions that were indistinguishable from those induced by
      hemoglobin, suggesting that reduction in normal NO levels is an important
      mechanistic factor. Overall, the presence of myocardial lesions represents a
      histopathologic finding that must be considered during the preclinical testing
      and development of new HBOCs.

PMID- 15508275
TI  - Measurements of evaporated perfluorocarbon during partial liquid ventilation by a
      zeolite absorber.
AB  - During partial liquid ventilation (PLV) the knowledge of the quantity of exhaled
      perfluorocarbon (PFC) allows a continuous substitution of the PFC loss to achieve
      a constant PFC level in the lungs. The aim of our in vitro study was to determine
      the PFC loss in the mixed expired gas by an absorber and to investigate the
      effect of the evaporated PFC on ventilatory measurements. METHOD: To simulate the
      PFC loss during PLV, a heated flask was rinsed with a constant airflow of 4 L
      min(-1) and PFC was infused by different speeds (5, 10, 20 mL h(-1)). An absorber
      filled with PFC selective zeolites was connected with the flask to measure the
      PFC in the gas. The evaporated PFC volume and the PFC concentration were
      determined from the weight gain of the absorber measured by an electronic scale.
      The PFC-dependent volume error of the CO2SMO plus neonatal pneumotachograph was
      measured by manual movements of a syringe with volumes of 10 and 28 mL with a
      rate of 30 min(-1). RESULTS: Under steady state conditions there was a strong
      correlation (r2 = 0.999) between the infusion speed of PFC and the calculated PFC
      flow rate. The PFC flow rate was slightly underestimated by 4.3% (p < 0.01).
      However, this bias was independent from PFC infusion rate. The evaporated PFC
      volume was precisely measured with errors < 1%. The volume error of the CO2SMO
      Plus pneumotachograph increased with increasing PFC content for both tidal
      volumes (p < 0.01). However for PFC flow rates up to 20 mL/h the error of the
      measured tidal volumes was < 5%. CONCLUSIONS: PFC selective zeolites can be used
      to quantify accurately the evaporated PFC volume during PLV. With increasing PFC
      concentrations in the exhaled air the measurement errors of ventilatory
      parameters have to be taken into account.

PMID- 15508276
TI  - Viscosity of animal erythrocyte suspensions mixed with a perflurocarbon emulsion.
AB  - Artificial blood substitutes (ABS) offer an alternative to donated blood.
      Increasing the oxygen carrying capacity of blood plasma through the addition of a
      Perfluorocarbon emulsion (PFE) is one approach in creating a blood substitute.
      The peripheral resistance of the circulatory system may be altered depending on
      the rheological properties of the ABS. Measurements of the rheological behavior
      of mixtures of a PFE, Oxygent, and erythrocyte suspensions were conducted at room
      temperature at different hematocrits using sheep (nonaggregating) and swine
      (aggregating) erythrocytes. The pure PFE was found to be shear thinning. Adding 6
      and 12 g per 100 mL of sheep blood at the various hematocrits increased the
      viscosity of the suspension from as low as 4% (6 g PFE/40% Hct) to as high as
      26.5% (12 g PFE/plasma). The nonaggregating sheep erythrocyte and PFE mixtures
      exhibited Newtonian behavior. Shear thinning behavior continued upon addition of
      6 and 12 g per 100 mL of swine blood at the various hematocrits, with a slight
      increase in viscosity in most cases. It was observed that adding 12 g of PFE
      (approximately 3 x intended clinical dose) to 40% Hct swine blood at room
      temperature led to a significant decrease in viscosity.

PMID- 15508277
TI  - Temporal effect of hemoglobin resuscitation on sepsis survival.
AB  - Hemoglobin (Hb)-based oxygen carriers are promising resuscitation fluids for
      hemorrhagic shock. However, infusion of large amounts of Hb-based material could
      interfere with reticuloendothelial function potentiating postresuscitation sepsis
      mortality. We investigated the temporal relationship between hemorrhage
      resuscitation and sepsis survival. Male SD rats were subjected to hemorrhage and
      resuscitated with shed blood volumes of purified human hemoglobin solution (HS).
      Sepsis was induced by cecal ligation and puncture (CLP) 24 h before, 0, 24, or 72
      h after hemorrhage/resuscitation (H/R) and survival was monitored. In additional
      animals with or without Hb resuscitation, hepatic heme oxygenase-1 (HO-1) gene
      expression and HO activity were assessed. Seven-day survival for animals
      resuscitated with HS prior to sepsis induction was significantly higher than
      other groups. Animals resuscitated with HS showed hepatic HO-1 gene expression
      while non-HS resuscitated animals did not. In addition, hepatic HO activity
      levels were significantly higher in HS resuscitated animals than non-HS
      resuscitated animals. In conclusion, HS resuscitation does not appear to enhance
      postresuscitation sepsis mortality. Rather, when conducted concomitantly or prior
      to sepsis, HS resuscitation appears to improve survival from a subsequent sepsis
      challenge.

PMID- 15508278
TI  - Immobilization of cholesterol oxidase on cellulose acetate membrane for free
      cholesterol biosensor development.
AB  - This article describes the immobilization of cholesterol oxidase on a cellulose
      acetate (CA) membrane activated by Sodium periodate, ethylenediamine, and
      glutaraldehyde etc. The properties of the immobilized enzyme membrane were
      investigated. The factors affecting the activity of immobilized enzyme such as
      the concentration of glutaraldehyde, the concentration of enzyme used during
      immobilization, temperature, pH, and immobilizing time etc. were also studied.
      The immobilized COD membrane has been used to construct fibre-optic fluorescent
      biosensor.

PMID- 15508279
TI  - Acetylcholinesterase (AChE) electrodes based on gelatin and chitosan matrices for
      the pesticide detection.
AB  - Enzyme electrodes for the determination of organophosphate pesticides were
      developed by using acetylcholinesterase (AChE) in combination with a pH
      electrode. AChE was immobilized on the surface of pH electrode by using gelatin
      and chitosan membranes, respectively. The measurement system is based on
      potentiometric detection of the inhibiting properties of organophosphates on
      enzyme activity. The phosphate buffer (2.5mM, pH 8.0) and the borate buffer
      (2.5mM, pH 8.5) at 25 degrees C were established as providing the optimum
      conditions for the gelatin and chitosan based biosensor systems, respectively.
      Furthermore, operational, thermal, and organic phase stabilities were also
      tested. Linear ranges for different organophosphates such as malathion, parathion
      methyl, and methamidophos were detected by using both types of biosensor system.
      Moreover, as well as accuracy, the regeneration conditions by using pyridine-2
      aldoximethiodide (PAM-2) as a reactivating agent for the inhibited electrodes
      were also investigated.

PMID- 15508280
TI  - Catalase immobilization in cellulose acetate beads and determination of its
      hydrogen peroxide decomposition level by using a catalase biosensor.
AB  - Catalase enzyme (EC 1.11.1.6) was immobilized by entrapping in cellulose acetate
      beads. This organic matrix is highly resistant to mechanical stability and can be
      used under various conditions. Initial studies were conducted to examine the
      immobilization ability of catalase on the matrix previously activated with a
      series of reagent normally and the best results were obtained with the beads
      activated with Ce(SO4)2. In the optimization studies of the immobilized enzyme
      optimum pH and temperature were found as pH:7.0 (Tris-HCl, 50 mM) and 35 degrees
      C. In the characterization studies of the immobilized enzyme some parameters such
      as storage and thermal stability were investigated. Finally, the immobilized
      enzyme was used for the decomposition of hydrogen peroxide in milk samples and
      also by using a catalase biosensor prepared the decomposition level of hydrogen
      peroxide was detected.

PMID- 15508281
TI  - Immobilization of catalase by entrapping in alginate beads and catalase biosensor
      preparation for the determination of hydrogen peroxide decomposition.
AB  - In this study, catalase enzyme was immobilized by entrapping in alginate beads in
      the presence of gelatin. In the optimization studies of the bioactive layer
      immobilized some parameters such as enzyme amount, alginate, gelatin, and
      crosslinking agent glutaraldehyde amount were determined as 700 U/mL, 2.0%, 18
      mg/mL, and 5.0%, respectively. Effects of pH and temperature on the
      immobilization were also investigated. In the characterization studies of the
      immobilized enzyme storage and thermal stability experiments were done. The
      immobilized enzyme was used for the decomposition of hydrogen peroxide in milk
      samples and also by using a catalase biosensor prepared by the decomposition
      level of hydrogen peroxide was detected.

PMID- 15508282
TI  - Polyurethane vascular grafts with thorough porosity: does an internal or an
      external membrane wrapping improve their in vivo blood compatibility and
      biofunctionality?
AB  - Using a freeze-drying multiple-step technique, porous polyurethane vascular
      grafts 1.5 mm in diameter with different internal and external surface
      characteristics were fabricated: Type A: with thorough porosity, Type B: with
      internal membrane wrapping and Type C: with external membrane wrapping. One
      centimeter long tubes of each three types of grafts were implanted into the infra
      renal abdominal aorta of rats for periods of 2, 4, 8 weeks. All the grafts were
      patent at harvesting. At the end of 2 weeks postimplantation, the endothelial
      cells layer developed inside the grafts about 1.2 mm apart from either the distal
      anastomosis side or both the distal and proximal anastomoses. They spreaded to
      the middle part of the one cm-long graft at 4 weeks. The luminal surfaces were
      entirely covered by a layer of endothelial cells at 8 weeks. Smooth muscle cells
      also migrated underneath the endothelial cell layer through the inner surface
      from the anastomosis and grew into the porous wall to generate a biocomposite
      blood conduit. Type B grafts with an internal membrane wrapping, developed a
      thicker, easy to lift intima after all the durations of implantation because the
      internal capsule was poorly anchored to the device. It is therefore of paramount
      importance that a porous structure is exposed to the blood flow to permit an
      adequate healing together with a good anchorage of the internal capsule.

PMID- 15508283
TI  - Liquid state bioconversion of sewage treatment plant sludge in batch fermenter
      and shake flask.
AB  - A study on liquid state bioconversion of sewage treatment plant (STP) sludge was
      assisted to evaluate the performance of batch fermenter compared to shake flask
      in a laboratory. Bioconversion of STP sludge was highly influenced by the mixed
      fungal culture of Penicillium corylophilum and Aspergillus niger after 4 days of
      treatment. The results showed that about 24.9 g kg(-1) dry sludge cake (DSC) was
      produced with enrichment of fungal biomass protein in fermenter while 20.1 g kg(
      1) in shake flask after 4 days of fungal treatment. The effective biodegradation
      of STP sludge was recorded in both fermenter and shake flask experiment compared
      to control (uninnoculated sample). The results presented in this study revealed
      that the overall performance of fermenter in terms of sludge cake (biosolids)
      accumulation and biodegradation of STP sludge was higher than the shake flask.

PMID- 15508284
TI  - [Smoking cessation and smoke-free environment--a necessity for the improvement of
      public health!].

PMID- 15508285
TI  - [Insulin pump treatment in Denmark].

PMID- 15508286
TI  - [Axillary hyperhidrosis].

PMID- 15508287
TI  - [Smoking cessation and chronic obstructive pulmonary disease].

PMID- 15508288
TI  - [Antidepressants for smoking cessation].

PMID- 15508289
TI  - [Workplace smoking cessation].

PMID- 15508290
TI  - [Prevention of smoking among children and adolescents based on school programs].

PMID- 15508291
TI  - [The prevalence of passive smoking among pregnant women in Denmark on their first
      visit to the midwife].

PMID- 15508292
TI  - [Should physicians advise on smoking cessation? What do patients and the general
      population think?].

PMID- 15508293
TI  - [Preoperative smoking intervention: What do patients think? A qualitative study].

PMID- 15508294
TI  - [A prospective study of the association between smoking and later alcohol
      drinking in the Danish population].

PMID- 15508295
TI  - [Use of transpelvic vertical rectus abdominus musculocutaneous flap-plasty in the
      treatment of anal cancer].

PMID- 15508296
TI  - [Renal stone and primary hyperparathyroidism. Risk of renal stone before and
      after parathyroidectomy].

PMID- 15508297
TI  - [The cap got too small--a case of Paget's disease of the skull bones].

PMID- 15508298
TI  - [Acute carpal tunnel syndrome secondary to Staphylococcus aureus tenosynovitis].

PMID- 15508299
TI  - [Whipple's disease--a cause of culture-negative endocarditis].

PMID- 15508300
TI  - [Aminoglycosides to critically ill patients].

PMID- 15508301
TI  - [Mammography screening without overdiagnosis].

PMID- 15508302
TI  - [Drug interactions].

PMID- 15508303
TI  - Direct automatic screening of soils for polycyclic aromatic hydrocarbons based on
      microwave-assisted extraction/fluorescence detection and on-line liquid
      chromatographic confirmation.
AB  - An integrated screening-confirmation system for PAHs in soils is presented. The
      sample screening configuration comprises on-line microwave-assisted extraction of
      the selected pollutants, followed by continuous preconcentration and sample clean
      up on RP-C18. Those samples for which the total concentration is close to or
      above the threshold limit established (10 microg/g) are subjected to liquid
      chromatographic separation for confirmation. An evaluation of the qualitative
      data obtained was also carried out, by calculating the unreliability zone as well
      as the false positive and false negative rates. The whole method
      (extraction/determination/confirmation) was validated using industrial soil and
      harbour sediment certified reference materials (IRMM, European Commission CRM 524
      and CRM 535). Application to the screening of solid environmental samples with
      subsequent confirmation of the results is also presented.

PMID- 15508304
TI  - Evaluation of solid-phase extraction and stir-bar sorptive extraction for the
      determination of fungicide residues at low-microg kg(-1) levels in grapes by
      liquid chromatography-mass spectrometry.
AB  - A liquid chromatography-mass spectrometry method has been developed for
      determining bitertanol, carboxin, flutriafol, pyrimethanil, tebuconazole and
      triadimefon. The evaluation of both atmospheric pressure interfaces (API),
      atmospheric pressure chemical ionization (APCI) and electrospray (ESI) using
      positive and negative ionization modes, clearly shows that the studied pesticides
      are more sensitive using APCI in positive mode. Two procedures based on solid
      phase extraction (SPE) and stir-bar sorptive extraction (SBSE) have been assessed
      for extracting these compounds in grape. The recoveries obtained by SPE in
      samples spiked at the limit of quantification (LOQ) level ranged from 60 to 100%
      with relative standard deviation (R.S.D.s) from 7 to 17%. With the SBSE the
      recoveries obtained from samples spiked at LOQ level were between 15 and 100% and
      the R.S.D.s between 10 and 19%. The LOQs of most compounds are better by SPE
      (0.003-0.01 mg kg(-1)) than by SBSE (0.01 mg kg(-1) for all fungicides). Although
      SPE provided higher recoveries, lower R.S.D.s, best LOQs and is more rapid to
      carry out compared with SBSE, this last one has some advantages such as lower
      organic solvent consumption, and cleaner extracts. Results obtained applying both
      techniques to real samples are analogous.

PMID- 15508305
TI  - Influence of the column hold-up time measurement accuracy on the prediction of
      chromatographic band profiles.
AB  - The influence of the column hold-up time measurement accuracy on the
      determination of equilibrium isotherms by classical frontal analysis and the
      prediction of overloaded elution band profiles were investigated. The ideal model
      of chromatography in combination with a Langmuir isotherm was used. Breakthrough
      curves and overloaded elution profiles were computer generated with a known hold
      up time value (true hold-up time). Then these data were evaluated the same way as
      it is done with experimental chromatographic data where the true hold-up time is
      unknown, i.e. to determine the equilibrium isotherm by the frontal analysis
      procedure, to fit the isotherm data to the Langmuir model and then to predict
      chromatographic band profiles using, e.g. the ideal model of chromatography. A
      comparison of overloaded elution profiles obtained with different deviations of
      the hold-up time from its true value shows that the effect of its measurement
      error is significant in preparative liquid chromatography because the isotherm is
      usually strongly nonlinear in this case.

PMID- 15508306
TI  - Atmospheric pressure photoionization. II. Dual source ionization.
AB  - In this paper we describe results based on the combination of atmospheric
      pressure photoionization (APPI) with atmospheric pressure chemical ionization
      (APCI) and electrospray ionization (ESI). The main purpose of combining more than
      one ionizer is to extend the range of compounds that can be simultaneously
      analyzed. Three modes of operation are presented; use of either ionizer,
      simultaneous use of two ionizers, and rapid switching between ionizers during a
      single chromatographic run. The dual ionizer configurations only minimally affect
      the performance of either ionizer relative to the standard single-ionizer
      sources. However, it is observed that the operation of both ionizers together
      does not typically give the sum signal from either source operating alone. For
      APCI/APPI the signal can range from less than that of either source alone to the
      sum of the two individual sources. For ESI/APPI, we observed large suppressions
      of the ESI multiply-charged signal of proteins when the APPI source was on. These
      behaviors are presumed to be due to the interaction of the initially formed ions
      by both sources and attests to the importance of ion-molecule reactions that
      occur during and after the primary ionization events. We give examples of
      compounds that are preferentially ionized by either APPI, APCI or ESI and present
      thermochemical arguments based on molecular structure and functionality to
      explain this behavior. The dual source is also shown to be able to operate in
      negative ion mode opening up the potential to conduct wide ranging chemical
      analyses.

PMID- 15508307
TI  - Separation of racemic 2,4-dinitrophenyl amino acids on 9-O
      (phenyloxycarbonyl)quinine-bonded carbon-clad zirconia in reversed-phase liquid
      chromatography.
AB  - Zirconia is known to be one of the best materials for the chromatographic support
      due to its excellent chemical, thermal, and mechanical stability. In this work,
      we report preparation and use of 9-O-(phenyloxycarbonyl)quinine-bonded carbon
      clad zirconia (QNCZ) as a chiral stationary phase (CSP) for separation of N-(2,4
      dinitrophenyl) (DNP)-amino acids (AAs) enantiomers in reversed-phase liquid
      chromatography. Retention and enantioselectivity of the QNCZ CSP were compared
      with those of quinine 3-triethoxysilylpropylcarbamate-coated zirconia (QNZ) and
      quinine 3-triethoxysilylpropylcarbamate-bonded silica (QNS). The QNCZ CSP showed
      in general the better enantioselectivity for most of the amino acids studied.

PMID- 15508308
TI  - Automated peak tracking for comprehensive impurity profiling in orthogonal liquid
      chromatographic separation using mass spectrometric detection.
AB  - The presence and quantity of impurities in pharmaceutical drugs can have a
      significant impact on their quality and safety. With the continuous pressure for
      increased industry productivity, there is urgent need for a systematic and
      comprehensive drug impurity profiling strategy. We report here our development of
      the fully automated Comprehensive Orthogonal Method Evaluation Technology (COMET)
      system. The system includes five columns, seven orthogonal HPLC methods, and
      hyphenated UV-MS detections, which provides automated generic impurities
      screening for any drug sample. An automated MS peak tracking approach by program
      based mass spectral interpretation is devised to unambiguously track impurities
      among all orthogonal HPLC methods. The program passes electro-spray ionization
      mass spectra (ESI-MS) through four sequential decision-making mass ion tests and
      determines molecular weights for every peak. The system reduces the time required
      to obtain impurity profile from weeks to days, while the automated MS peak
      tracking takes only minutes to interpret all MS spectral data of interest. Up-to
      date, impurity contents of 56 in-development drug candidate samples have all been
      successfully illustrated by COMET, which contained more than 500 chemical
      entities. The program is able to track more than 80% of the compounds
      automatically with majority of the failure due to insufficient ionization for
      some impurities by ESI. This system is well suited for efficient drug development
      and ensuring the quality and safety of drug products.

PMID- 15508309
TI  - Determination of beauvericin and four other enniatins in grain by liquid
      chromatography-mass spectrometry.
AB  - A method is described using LC-MS-MS for the detection of five different
      enniatins in grain. The method involves extraction of the fungal secondary
      metabolites using acetonitrile-water and quantification using LC-MS-MS with
      atmospheric pressure chemical ionisation, without further treatment of sample
      extracts. The selected ion reaction of [M + NH4]+ to [M + H]+ was utilised in the
      specific detection of the compounds. Mean recoveries (n = 5-12) of enniatins from
      spiked grain samples over a period of six months were 99-115%, 86-131%, 97-113%,
      73-100% and 78-114% for beauvericin, enniatin A, A1, B and B1, respectively. The
      limits of detection were 3.0 microg/kg for beauvericin, enniatin A, B and B1 and
      4.0 microg/kg for enniatin A1, which corresponds to on-column detection limits of
      7.5 pg and 10 pg, respectively.

PMID- 15508310
TI  - Application of internal quality control to the analysis of quaternary ammonium
      compounds in surface and groundwater from Andalusia (Spain) by liquid
      chromatography with mass spectrometry.
AB  - A method has been developed for the simultaneous determination of paraquat (PQ),
      deiquat (DQ), chlormequat (CQ) and mepiquat (MQ) in water samples by liquid
      chromatography (LC) coupled with electrospray ionization mass spectrometry (MS).
      The LC separations of the target compounds, as well as their MS parameters, were
      optimized in order to improve selectivity and sensitivity. Separation was carried
      out in a Xterra C8 column, using as mobile phase methanol-heptafluorobutyric acid
      (HFBA) in isocratic mode. The molecular ion was selected for the quantitation in
      selected ion monitoring (SIM) mode. Off-line solid-phase extraction (SPE) was
      applied with silica cartridges in order to preconcentrate the compounds from
      waters. Detection limits were in the range 0.02-0.40 microg l(-1). Recovery range
      varied between 89 and 99.5% with precision values lower than 6%. The method has
      been applied successfully to the analysis of both surface and groundwater samples
      from agricultural areas of Andalusia (Spain), using well defined internal quality
      control (IQC) criteria. The results revealed the presence of deiquat and paraquat
      in some samples.

PMID- 15508311
TI  - Gas chromatographic evaluation of pesticide residue contents in nectarines after
      non-toxic washing treatments.
AB  - Washing with aqueous solutions of citric acid, ethanol, glycerol, hydrogen
      peroxide, potassium permanganate, sodium metabisulfite, sodium laurylsulfate
      (SLS), sodium hypochlorite, and urea is evaluated for pesticide residue reduction
      in nectarines and compared with simple tap water washing. Residues of pesticides
      commonly utilized in nectarines (chlorpyrifos, fenarimol, iprodione, malathion,
      methidathion, myclobutanil, parathion and pirimicarb) are extracted with ethyl
      acetate and anhydrous sodium sulfate, extract is concentred and analyzed by GC
      with nitrogen-phosphorus detection. The formation of possible toxic by-products
      (chlorpyrifos oxon, malaoxon, methidaoxon and paraoxon methyl) is studied by GC
      MS. No toxic by-products are identified in the extracts of the washed samples for
      the washing-time and concentrations studied, but high levels of sodium
      hypochlorite, hydrogen peroxide and potassium permanganate form oxons from the
      organophosphorus pesticides. Ethanol, glycerol and SLS solutions removed near the
      50% of the pesticide residues. The other solutions were not more effective than
      tap water washing. The amount of pesticide removed by washings is related to its
      water solubility and octanol-water partition coefficient.

PMID- 15508312
TI  - Determination of chlorpyrifos 20% EC (Dursban 20 EC) in scented rose and its
      products.
AB  - The method for determination of chlorpyrifos is validated and dissipation
      behaviour of residue in scented rose and percent transfer in different products
      is described. GC-electron-capture detection with a HP-1, 30 m x 0.53 mm, 3.0
      microm capillary column and nitrogen at 1 ml/min was used in the study. Plant
      matrices studied were: leaves, flowers, soil, rose water, absolute and concrete.
      Detector response linearity and sensitivity, limit of detection and
      determination, percent recovery were determined based on area response (mm2) of
      the standard. Analytical field and laboratory samples (rose water by hydro
      distillation of the flowers, concrete and absolute by hexane extraction and
      condensation) were analysed for evaluation of the method. Samples were extracted
      with acetone, partitioned with water, saturated sodium chloride solution and
      dichloromethane. The organic layer was rotary-evaporated to 2 ml for cleanup with
      silica-carbon column. The column was eluted with dichloromethane-toluene-acetone
      (10:2:2, v/v/v) and the derived solution was rotary-evaporated to 5 ml for end
      analysis. Matrix enhancement effect was observed for leaf and soil samples for
      which corrective approach was followed to compensate for overestimation of the
      residue. Limit of detection for chlorpyrifos standard was 0.05 mg/l with good
      linearity of detector response (R2 = 0.99). Percent recovery ranged from 78 to
      117% in different plant matrices (fortification level 1, 4 and 8 mg/l).
      Dissipation behaviour showed that chlorpyrifos was below detection limit by the
      12th day of application on the scented rose with half life of 3.40 days on leaves
      and 3.10 days on flowers at 0.1% dosage. Percent transfer studies showed that
      5.71, 46.91 and 38.80% of the residue from flowers was transferred to rose water,
      concrete and absolute, respectively.

PMID- 15508313
TI  - Detection and identification of phenazone-type drugs and their microbial
      metabolites in ground and drinking water applying solid-phase extraction and gas
      chromatography with mass spectrometric detection.
AB  - A new analytical method applying in situ derivatization was developed to enable
      the extraction of polar drug metabolites from water samples by solid-phase
      extraction (SPE). An additional derivatization by silylation was used to enhance
      the sensitivity of analyte detection by gas chromatography-mass spectrometry (GC
      MS). Thus, the two metabolites 1,5-di-methyl-1,2-dehydro-3-pyrazolone (DP) and 4
      (2-methylethyl)-1,5-dimethyl-1,2-dehydro-3-pyrazolone (PDP), postulated for the
      degradation of phenazone and propyphenazone, were identified and detected up to
      the microg/L level in raw and drinking water samples from public water supply.

PMID- 15508314
TI  - Profiling analysis of oligosaccharides in antibody pharmaceuticals by capillary
      electrophoresis.
AB  - Carbohydrate chains in glycoprotein pharmaceuticals have important roles for the
      expression of their biological activities. Therefore, development of an
      assessment method for the carbohydrate chains is an important parameter for
      quality control of glycoprotein pharmaceuticals such as newly developed
      therapeutic antibodies. In this report, we applied capillary electrophoresis with
      laser-induced fluorescence detection to the analysis of carbohydrate chains after
      releasing with glycoamidase followed by derivatization with 3-aminobenzoic acid.
      We found that four major oligosaccharides present in antibody pharmaceuticals
      were successfully separated with good resolution. The present method showed good
      precision in both migration times and relative peak areas, and gave comparable
      accuracy with that using a derivatization method with 8-aminopyrene-1,3,6
      trisulfonate.

PMID- 15508315
TI  - Simultaneous separation of anions and cations by capillary electrophoresis with
      high magnitude, reversed electroosmotic flow.
AB  - A method for simultaneous separation and indirect detection of anions and cations
      by capillary electrophoresis (CE) is reported. An anodic electroosmotic flow
      (EOF) in excess of -100 x 10(-9) m2 V(-1) s(-1) was achieved by the addition of
      0.1 mM didodecyldimethylammonium bromide (DDAB) to the background electrolyte
      (BGE). This high magnitude EOF enabled rapid co-EOF separation of inorganic
      anions and counter-EOF separation of inorganic cations having high
      electrophoretic mobilities. Single-end injection of the sample at the capillary
      inlet and detection near the capillary outlet was used. Indirect photometric
      detection of cations was accomplished using a cationic probe (imidazole), with
      counter-ionic (Kohlrausch) indirect detection being used for anions. A mixture
      consisting of chloride, bromide, nitrate, lithium, magnesium, sodium, calcium,
      potassium, and ammonium was separated in less than 3.5 min using a background
      electrolyte comprising 6 mM imidazole, 12 mM hydroxyisobutyric acid, 0.1 mM DDAB,
      2 mM 18-crown-6 at pH 4.0, with indirect detection at 210 nm. The system was well
      suited to the separation and detection of inorganic cations, with limits of
      detection (LODs) in the range 0.92-4.65 microM and separation efficiencies from
      44,400-208,5000 theoretical plates. By contrast, LODs for inorganic anions ranged
      from 6.66 to 11.43 microM, with separation efficiencies of 2500-26,300.
      Analytical potential of the method is discussed.

PMID- 15508316
TI  - In situ matrix evaporation by isothermal distillation of high-purity reagents for
      the determination of trace impurities by ion chromatography.
AB  - In situ matrix evaporation of high-purity acids based on isothermal distillation
      was achieved in a high-density polyethylene (HDPE) container on a water bath, to
      avoid contamination from the laboratory environment. The solubility of water and
      acid vapours in glycerol due to co-association was utilized to achieve complete
      evaporation. All major sources which contribute to the process blank were taken
      care of in a simple and effective way. A 50-fold preconcentration with >99.9%
      matrix removal was achieved for the analysis of low-boiling acids, HCl, HF, HNO3
      and H2O2. The non-volatile ions NH4+, Li+, Na+, K+, Mg2+, Ca2+, SO4(2-) and PO4(3
      ) were determined by ion chromatograph with conductivity detection. The detection
      limits were 6-130 ng/l with recoveries of 85-110% for all ions studied.

PMID- 15508317
TI  - No downhill coast for data standards.

PMID- 15508318
TI  - Avoiding a war of words (and numbers): the uncertain future of terminologies and
      classifications.

PMID- 15508319
TI  - International accreditation: what's good practice in Sao Paulo is good practice
      in Istanbul.

PMID- 15508320
TI  - Name game: Canada's blueprint for a nationwide master person index.

PMID- 15508321
TI  - Hands across the water: Edna K. Huffman and the development of the medical record
      profession in Australia.

PMID- 15508322
TI  - Creating an HIM profession in the Sultanate of Oman.

PMID- 15508323
TI  - Career trailblazers: HIM opportunities for entrepreneurs.

PMID- 15508324
TI  - Does the privacy rule hinder patient care?

PMID- 15508325
TI  - On the line. Listing reported abuse cases on the accounting of disclosures (AoD).

PMID- 15508326
TI  - Defining the differences between the CPR, EMR, and EHR.

PMID- 15508327
TI  - The trouble with audit controls.

PMID- 15508328
TI  - Navigating a successful business turnaround.

PMID- 15508330
TI  - Coding dementia.

PMID- 15508329
TI  - The strategic importance of electronic health records management.

PMID- 15508331
TI  - More than code revisions in the 2004 changes to ICD-9-CM.

PMID- 15508332
TI  - Discovering HIM in South Africa.

PMID- 15508333
TI  - Laboratory diagnostic testing for HIV in East Africa.

PMID- 15508334
TI  - New indirect immunofluorescence assay as a confirmatory test for human
      immunodeficiency virus type 1.
AB  - BACKGROUND: Screening of blood and blood products for human immunodeficiency
      virus (HIV) is routinely performed using the enzyme-linked immunosorbent assay
      (ELISA), and the results confirmed by Western blot (WB). However, western blot is
      expensive and mostly performed in developed countries. A technique more superior
      or comparable to WB and adaptable to developing countries must be sought. In an
      effort to identify such a technique, this study determined the efficiency of
      indirect immunofluorescence assay (IFA) to detect antibodies to HIV-1. OBJECTIVE:
      To determine the accuracy and sensitivity of an in-house immunofluorescence assay
      (IFA) to detect antibodies to HIV-1 in plasma. DESIGN: A comparative study to
      evaluate the performance of indirect immunofluorescence assay (IFA) and western
      blot (WB) techniques in the detection of antibodies to HIV-1. SETTING: Kenya
      Medical Research Institute, Centre for Virus Research. The study was conducted
      between June and December 2001. METHODS: The evaluation of IFA as a technique for
      detecting antibodies to HIV-1 utilized a total of 400 samples. For these samples,
      IFA was compared with ELISA and particle agglutination (PA) (manuscript under
      preparation). Of the 400 samples, there were discrepant results in the three
      assays in only 36 samples. IFA was compared with Western blot (WB) to confirm the
      true HIV-1 serostatus in these 36 plasma specimens. The IFA technique used
      acetone-fixed HIV-1 infected MOLT-4 cells in one spot on a Teflon coated slide
      and uninfected MOLT-4 cells alone in a second spot to asses non-specific
      fluorescence. Western blot was performed according to the instructions of the
      manufacturer. RESULTS: The sensitivity and specificity of IFA based on 36 plasma
      specimens tested was 71.4% and 100% respectively. All samples that were HIV
      seronegative by WB were also HIV seronegative by IFA. However, two (5.6%) samples
      were HIV seronegative by IFA but seropositive by WB. CONCLUSION: The data
      obtained show that IFA can be used as a primary confirmatory test in Kenya.

PMID- 15508335
TI  - Assessment of clinical case-definition for HIV/AIDS in Tanzania.
AB  - OBJECTIVE: To evaluate the usefulness of World Health Organisation (WHO's)
      clinical case-definition (CCD) for AIDS in a private hospital. DESIGN: A
      prospective study. SETTING: Shree Hindu Mandal Hospital, Dar es Salaam, Tanzania.
      SUBJECTS: A total of 601 patients (> 14 years) were studied from January 1995 to
      December 1997. METHODS: Using HIV test results as a reference standard,
      sensitivity, specificity, positive predictive values (PPV) and negative
      predictive values of signs and symptoms were calculated. Multiple logistic
      regression was used to determine a set of predictive symptoms and signs. Stepwise
      logistic regression modelling was used to choose the final model. RESULTS: The
      frequently occurring signs and symptoms among the 473 sero-positive patients were
      fever (226), oral candidiasis (167), weight loss (161), chronic cough (157),
      diarrhoea (100) and pulmonary tuberculosis in 69 cases. The presence of anorectal
      lesions and the rarity of pneumocystis carinii pneumonia in this study are
      important findings. Seven clinical characteristics predicted HIV infection. These
      included pulmonary tuberculosis (p=0.009), lymphadenopathy (p=0.007), diarrhoea
      (p=0.000), chronic cough (p=0.001), dermatitis (p=0.003), herpes zoster (p=0.01)
      and oral candidiasis (p=0.000). CONCLUSIONS: A greater number of HIV positive
      patients presented with signs and symptoms different from those proposed by WHO's
      CCD were observed in this study. With environmental pathogens varying from one
      geographical region to another and new ones appearing, opportunistic disease
      cannot be constant in AIDS patients. Therefore, AIDS diagnosis based on clinical
      case definition alone without at least one positive HIV antibody test is
      inaccurate and no longer justified.

PMID- 15508336
TI  - Feasibility of medical male circumcision in Nyanza Province, Kenya.
AB  - BACKGROUND: Over forty observational studies have reported a protective effect of
      male circumcision against HIV-I acquisition, leading some to suggest that male
      circumcision be added to the limited armamentarium of HIV prevention strategies.
      OBJECTIVES: To evaluate the feasibility and requirements of implementing medical
      male circumcision in Nyanza Province of Kenya a quasi-experimental design was
      implemented to assess clinicians' knowledge of male circumcision and to assess
      the effectiveness of a one day educational intervention in one district. A cross
      sectional survey assessed the availability of necessary instruments and surgical
      supplies. RESULTS: None of the participating ten health facilities had all the
      necessary instruments and supplies to safely perform male circumcisions. Though
      most clinicians reported training about circumcision, most lacked sufficient
      knowledge to perform the procedure, and few were familiar with the process of
      informed consent. We demonstrated that a didactic educational workshop
      significantly improved providers' knowledge of male circumcision. CONCLUSIONS:
      Since increasing numbers of young men and parents are requesting male
      circumcision services in many parts of sub-Saharan Africa, health providers must
      undergo further training in the performance of the procedure and the process of
      informed consent. Many health facilities will have to be provided with the
      instruments and supplies necessary to perform male circumcision safely.

PMID- 15508337
TI  - Dental caries in six, 12 and 15 year old Venda children in South Africa.
AB  - BACKGROUND: Oral diseases is still a major problem in most developing countries.
      Within the Republic of South Africa, there remains areas where few or no studies
      have been done on the oral health status. The emerging district health system
      with decentralisation of health services to address past inequity in health care
      in South Africa also provides compelling case for data collection at regional
      levels. OBJECTIVES: To assess the prevalence and severity of dental caries of
      school children; determine the caries patterns of the study population and to
      provide useful data for the planning of oral health services in this region.
      DESIGN: Descriptive analytical study. SETTING: School children in the Donald
      Fraser Health District, Venda in the Northern province, Republic of South Africa.
      SUBJECTS/METHODS: A total of 519 school children in the age groups 6, 12 and 15
      years were examined by a calibrated examiner for dental caries using WHO
      diagnostic criteria. Both the schools, which were divided into rural and peri
      urban locations and the children that participated were randomly selected.
      RESULTS: A mean dmft(sd) of 2.68(3.29) in six year olds and a mean DMFT (sd)
      scores of 0.61(1.50) and 1.26 (2.18) were recorded in the 12 and 15 year olds
      respectively. In the six year olds the upper anterior teeth showed highest
      susceptibility to caries, clearly indicating that black children suffer from
      early infant caries. At ages of 12 and 15 the mandibular molars were the teeth
      most affected. The decayed component constituted the main part of the dmft and
      DMFT scores. Ninety-nine percent of these lesions were untreated and the
      restorative care was almost nil. CONCLUSION: An important finding was the
      doubling of the mean DMFT from the 12-year-olds to 15-year olds and the caries
      levels for all age groups was higher than the provincial average. The treatment
      required were mostly extractions and simple fillings, the majority of which could
      be managed by dental auxiliaries using the Atraumatic Restorative Treatment
      Technique. This study indicates that preventive oral health measures should be
      implemented on the younger age groups in order to control dental caries.

PMID- 15508338
TI  - Preliminary studies on the biting activity and transmission of Onchocerca
      volvulus by Simulium neavei (diptera: simuliidae) in Kashoya-Kitomi focus,
      Western Uganda.
AB  - OBJECTIVE: To determine the biting activity and onchocerciasis transmission in
      Kashoya-Kitomi focus, Western Uganda. DESIGN: Cross-sectional survey in randomly
      selected sites. SETTING: Three districts in Western Uganda. METHOD: Crab trapping
      and examination for immature stages of Simulium neavei and full day human bait
      catches and dissections were conducted at three sites. RESULTS: A total of 338
      crabs were caught and out of this 372 (95.9%) were positive with immature stages
      of S. neavei with mean S. neavei/crab of 6.9. High biting density of S. neavei
      was observed in the two sites in Kabarole and Mbarara districts whereas an
      extremely low density was observed at a site in Bushenyi. Diurnal biting pattern
      revealed two peaks in the morning (09:00-10:00 hours.) and in the late afternoon
      (14:00-15:00 hours.) with a mid-day lull. The infection/infective rates were
      53.3/11.0%, 30.7% to 7.8% and 20.0/0% for sites in Mbarara, Kabarole and Bushenyi
      districts, respectively. Monthly biting rates/ Transmission potentials for
      Mbarara, Kabarole and Bushenyi districts were 6231/5437, 9244/2916 and 247/0.
      CONCLUSION: There was high transmission of onchocerciasis observed in Kashoya
      Kitomi focus despite the ongoing ivermectin treatment. The need for improved
      chemotherapeutic coverage and instituting other control measures may be
      necessary.

PMID- 15508339
TI  - Nutritional status, functional ability and food habits of institutionalised and
      non-institutionalised elderly people in Morogoro Region, Tanzania.
AB  - OBJECTIVE: To determine nutritional status, food habits and functional abilities
      of the institutionalised and non-institutionalised elderly. DESIGN: A cross
      sectional population survey. SETTING: Free living and institutionalised elderly
      of Morogoro municipality, Tanzania. SUBJECTS: A total of 100 elderly people,
      fifty institutionalised and fifty non-institutionalised were included. Gender
      distribution was of equal numbers. MEASUREMENTS: Anthropometric measurements of
      weights and heights were taken to enable calculation of Body Mass Index (BMI) of
      each subject. Questionnaires were used to collect information on types of foods,
      amount and frequency of consumption and functional abilities of the elderly.
      Amount of food consumed was expressed in grams per person per day. RESULTS: There
      were significant differences (p=0.001) in nutritional status between the
      institutionalised and the non- institutionalised males, but this relationship did
      not exist among the females. Similarly, 30% and 26% of the institutionalised
      males and females, respectively, and none of the non- institutionalised males was
      observed to be overweight. On the other hand, 39% and 23% of the non
      institutionalised males and females, respectively, were underweight or
      malnourished. Consumption of sardines was higher (p=0.05) among the
      institutionalised subjects, but the situation was opposite for the case of
      fruits. Alcohol consumption was higher (p<0.05) among non- institutionalised
      subjects in both sexes. No difference was noted in consumption of beans,
      vegetables, cereals and meat. The most common functional disability was urinary
      incontinence (36%) while feeding (5%) was the least common. The most affected by
      urinary incontinence were institutionalised male subjects. CONCLUSION: There was
      a great variation between elderly people who are cared for in institutional
      centres and those who are cared for by their relatives in terms of nutritional
      status, reflected by their BMI levels. The institutionalised ones appear to be
      better off than their counterparts. However, this condition is not equally
      reflected in their eating habits. Generally, most of the elderly have poor or no
      source of income, which make them to have poor living conditions. They are also
      faced with problems of functional disabilities of which urinary incontinence was
      more common among males.

PMID- 15508340
TI  - Retinitis pigmentosa in Benin, Nigeria.
AB  - OBJECTIVES: To determine the mode of presentation and degree of visual impairment
      of retinitis pigmentosa in Nigerians. DESIGN: A prospective, non-comparative
      study. SETTING: University of Benin Teaching Hospital, Benin City, Nigeria.
      SUBJECTS: Thirty Nigerian patients with a diagnosis of retinitis pigmentosa who
      presented at the Eye Clinic of the Ophthalmology Department of the University of
      Benin, Teaching Hospital, Benin City, Nigeria over a three year period (July 1997
      June 2000) were included in the study. The clinical features and mode of
      presentation were noted. The examination included visual acuity, slit lamp
      examination and fundoscopy. MAIN OUTCOME MEASURES: Presenting symptoms and signs,
      visual acuity. RESULTS: The degree of visual impairment and clinical features in
      thirty Nigerians with retinitis pigmentosa seen at the University of Benin
      Teaching Hospital, Benin City, Nigeria were studied. There were twenty males and
      ten females. The age range was 14 to 71 years (mean 36.7 years +/- 14.8 years).
      Fifteen patients (50%) had visual acuity of less than 3/60 while only seven
      (23.3%) had visual acuity of 6/12 or better. The commonest mode of presentation
      was poor vision in 90% of the patients followed by night blindness in 56.7%.
      Others were headaches, flashes of light and floaters. CONCLUSION: The degree of
      visual loss in Nigerians with retinitis pigmentosa is severe and may be related
      to the long duration of the disease and age of the patients at presentation.
      Health education of the public and patients about the need for early presentation
      to hospital and the use of vitamin A and carbonic anhydrase inhibitors are
      recommended.

PMID- 15508341
TI  - Posterior cranial fossa tumours in children at Kenyatta National Hospital,
      Nairobi.
AB  - BACKGROUND: The management of children with posterior fossa tumours is a
      challenge to health care professionals worldwide. Difficulties in diagnosis
      especially in children less than three years is well documented. Limited
      diagnostic modalities and lack of awareness of the symptoms and signs as well as
      societal perception of children's complaints contributes to late presentation.
      Kenyatta National Hospital Neurosurgical unit is the only specialized unit among
      the public hospitals in Kenya where such patients are referred. OBJECTIVE: To
      review the management of posterior fossa tumours in children at Kenyatta National
      Hospital. DESIGN: A retrospective analysis of children treated for posterior
      fossa tumours at the neurosurgical unit of Kenyatta National Hospital between
      1996-2003. SETTING: Neurosurgery unit, Kenyatta National Teaching and Referral
      hospital. RESULTS: Thirty seven children were treated for posterior fossa tumours
      between 1998 and 2003. Twenty four were females while thirteen were males giving
      a male: female ratio of 1:1.8. The age varied between 2-16 years with a mean of
      6.7 years. Cerebellar symptoms were the most common mode of presentation (30%)
      followed by headaches and vomiting. Twenty percent of our patients were blind at
      presentation probably due to chronic effects of raised intracranial pressure. Out
      of 11 patients with histological diagnosis of meduloblastomas, over 99%, were
      females and only one was a male. Astrocytomas were evenly distributed at five
      males and six females. The mean duration of symptoms was 3.7 months while it took
      eight weeks between time of diagnosis and treatment. CONCLUSION: Posterior fossa
      tumours in our set-up are more common in females than in males, M:F ratio of
      1:1.8. Over 90% of medulloblastomas are found in female children making it a
      predominantly female tumour as opposed to available literature. The delay in
      diagnosis is probably due to lack of information both to the parents and health
      care providers and expensive diagnostic tools. A high index of suspicion, and a
      good history and clinical examination is required in the diagnosis of posterior
      fossa tumours in children especially those below three years.

PMID- 15508342
TI  - Laparoscopic assisted vaginal hysterectomy for benign uterine pathology: is it
      time to change?
AB  - OBJECTIVE: To determine the acceptability and outcome of laparoscopic assisted
      vaginal hysterectomy at the Aga Khan Hospital, Nairobi. DESIGN: A retrospective
      case analysis. SUBJECTS: Two hundrend and twenty nine cases of laparoscopic
      assisted hysterectomy were undertaken at various hospitals in the presence of the
      principal author from May 2000 to December 2003. Of these 149 (65.06%) were
      performed at the Aga Khan Hospital, Nairobi. These cases have been reviewed,
      analysed and presented. EXCLUSIONS: All cases performed at the various other
      hospitals were excluded, along with those cases of laparoscopic assisted vaginal
      hysterectomy which are now being performed by other consultants obstetricians and
      gynaecologists, on their own and who have now learnt the technique RESULTS: Over
      the last three years, 149 cases of laparoscopic assisted vaginal hysterectomy
      were undertaken at the Aga Khan Hospital, Nairobi. Annual case load increased
      from three cases in 2000, to 71 cases by December, 2003. Fifty one percent of the
      patients were between 46 to 50 years of age, while 93.9% were para 2 + 0 and
      above. Menorrhagia was the presenting complaint in 55.7%. The operative procedure
      was performed in 91 to 120 minutes in 58.3% of the cases. Hospital stays were two
      nights in 95.3%. The complications encountered were bladder injury (3.4%), bowel
      injury (1.3%), port site herniation (0.67%) and a delayed recognition of bladder
      injury (0.67%). CONCLUSION: In Kenya, laparoscopic surgery is gradually being
      accepted by gynaecologists and general surgeons. The conversion from total
      abdominal hysterectomy to laparoscopic assisted vaginal hysterectomy for benign
      uterine pathology is now becoming more popular amongst gynaecologists and
      patients. With time laparoscopic assistance during hysterectomy will become the
      norm.

PMID- 15508343
TI  - Cervical spinal tuberculosis with tuberculous otitis media masquerading as otitis
      externa malignans in an elderly diabetic patient: case report.
AB  - Extrapulmonary manifestation of tuberculosis (Tb), a medieval disease, occurs in
      every part of the body with varying degree of frequency but commonly in the
      pleural and lymph nodes. When it occurs in bones thoracolumbar vertebrae is the
      usual site of involvement. Other bones are less involved hence seldomly reported.
      This is true for other organs and parts of the body including larynx, pharynx
      nose and the middle ear. More importantly, isolated extrapulmonary tuberculosis
      without pulmonary involvement is uncommon. The case of a 65 year old Nigerian
      trader who presented with headache, chronic ear ache with otorrhoea, persistent
      neck pain and found to be diabetic on further evaluation is presented. She was
      hitherto managed as a case of otitis external malignans without any improvement
      but rather her clinical condition worsened with evidence of cervical vertebra
      destruction and multiple cranial nerve palsies without pulmonary tuberculosis.
      Prompt and effective response to anti tuberculosis drugs informed the diagnosis
      of tuberculosis of the cervical vertebra and tuberculous otitis media with
      multiple cranial nerve palsies. This case underscores the value of high index of
      suspicion, thorough and complete clinical evaluation in any patient with chronic
      symptoms and signs unresponsive to conventional treatment.

PMID- 15508344
TI  - Schistosoma mansoni of the conus medularis: case report.
AB  - A six year old girl was admitted to the Kenyatta National Hospital paediatric
      unit with history of headaches, fever, neck stiffness and paraesthesias of the
      lower limbs. She was empirically commenced on antimeningitic treatment. Her
      neurological state deteriorated over a period of two months to paraparesis and
      paraplegia of the lower limbs with urinary and stool incontinence. A neurology
      review revealed a sensory level at T10 with power grade 2 in the lower limbs. A
      myelogram revealed a block of contrast at T12. An impression of cord compression
      by an intraspinal tumour was made. Laminectomy and posterior midline myelotomy
      was performed. At operation a greyish-white intramedullary mass lesion was found.
      Histology revealed a schistosoma mansoni ovum surrounded by granulomatous tissue
      with giant cells and polymorphoneuclear leucocytes. The child was commenced on
      paziquantel 1000 mg and dexamethasone 24 mg per day in divided doses. There was
      marked neurological improvement and the patient went home one month later. She
      was able to walk without support and was continent of urine and stool at the time
      of discharge.

PMID- 15508345
TI  - Testicular torsion: case report.
AB  - This is a report of bilateral testicular torsion. The objective of the report is
      to highlight the serious implications of misdiagnosis of testicular torsion.
      Other than loss of the testis due to necrosis in unilateral torsion,
      immunological damage of the opposite testis occurs. Early, accurate diagnosis,
      and institution of the appropriate treatment are desirable to prevent total loss
      of reproductive potential in the affected male.

PMID- 15508346
TI  - Milrinone reduces cerebral vasospasm after subarachnoid hemorrhage of WFNS grade
      IV or V.
AB  - The preventative effect of cisternal irrigation with milrinone against vasospasm
      was evaluated in 12 patients with subarachnoid hemorrhage (SAH) of World
      Federation of Neurosurgical Societies grade IV or V treated between September
      1999 and September 2000. All aneurysms were clipped or embolized within 72 hours
      of the onset of SAH. Inlet and outlet tubes were placed in either the
      supratentorial cisternal space, lateral ventricle, or spinal subarachnoid space.
      Lactated Ringer solution containing urokinase (120 IU/ml), ascorbic acid (3.5
      mg/ml), and milrinone (3.6 microg/ml) was continuously infused at 30 ml/hr for as
      long as 2 weeks. Angiographical vasospasm was detected in only two of the 11
      patients who received milrinone irrigation and underwent postoperative
      angiography. Vasospasm may have resulted from irrigation obstruction associated
      with pneumocephalus in one patient and clot in the sylvian fissure in the other
      patient. The outcome of the milrinone irrigation therapy was significantly better
      than that of the conventional therapy. This study suggests that cisternal
      irrigation with milrinone is safe and effective, and reduces the occurrence of
      vasospasm in patients with poor grade aneurysmal SAH.

PMID- 15508347
TI  - E, N-cadherins and beta-catenin expression in medulloblastoma and atypical
      teratoid/rhabdoid tumor.
AB  - Cadherins are cell-surface glycoproteins that mediate Ca2+-dependent, homophilic
      cell-cell adhesion. The classical cadherins, E- and N-cadherins, bind to beta
      catenin, the lining protein. Dysfunctional expression of these factors seems to
      be related to tumor invasion and metastasis. This study examined the relationship
      between changes in E- and N-cadherins, and catenin expression, and biological
      behavior in medulloblastomas and atypical teratoid/rhabdoid tumors. Specimens of
      13 medulloblastomas and two atypical teratoma/rhabdoid tumors were collected and
      stained immunohistochemically to detect E- and N-cadherins, and beta-catenin.
      None of the medulloblastomas were immunoreactive for E-cadherin, but both
      atypical teratoma/rhabdoid tumors were immunoreactive for E-cadherin at the cell
      cell borders where epithelial differentiation occurred. In contrast, N-cadherin
      and beta-catenin were present at the cell-cell borders in 12 of the 13
      medulloblastomas and both atypical teratoma/rhabdoid tumors. Nuclear beta-catenin
      staining was not present in the medulloblastomas or atypical teratoma/rhabdoid
      tumors. There was no significant difference in the Ki-67 staining index between
      patients with medulloblastomas showing high and low immunoreactivity for N
      cadherin and beta-catenin. Moreover, immunoreactivity for N-cadherin and beta
      catenin increased with dissemination in the medulloblastomas. Low
      immunoreactivity in medulloblastomas tended to be associated with a better
      prognosis. These results suggest that expression of E-cadherin is useful for the
      differential diagnosis of atypical teratoma/rhabdoid tumor and medulloblastoma,
      and the expression of N-cadherin or beta-catenin may be related to the biological
      behavior of medulloblastomas.

PMID- 15508348
TI  - Neuroendoscopic transventricular surgery for suprasellar cystic mass lesions such
      as cystic craniopharyngioma and Rathke cleft cyst.
AB  - Cystic mass lesions in the suprasellar cistern are often associated with
      neurological deficits, cognitive disorders, and endocrinological impairments.
      Many surgical approaches are available to treat these mass lesions, but are
      technically difficult and cannot remove the lesion completely without risking
      damage to neurological and endocrinological functions due to the proximity to the
      surrounding structures. Neuroendoscopic transventricular surgery was performed
      using a ventricular fiberscope for three patients with craniopharyngiomas and two
      patients with Rathke cleft cysts, with gamma knife radiosurgery for
      craniopharyngiomas. The endoscopic transventricular approach is safe and
      minimally invasive for congenital benign suprasellar cystic lesions, especially
      arachnoid cysts.

PMID- 15508349
TI  - Cortical blindness during coil embolization of an unruptured intracranial
      aneurysm--case report.
AB  - A 62-year-old woman suffered transient cortical blindness during coil
      embolization for a saccular aneurysm in the posterior circulation, with cerebral
      angiography using non-ionic contrast material. Just before completion of the
      procedure, the patient showed abrupt onset of restlessness and blindness. At this
      point 150 ml of contrast material had been injected into the left vertebral
      artery. Immediate computed tomography showed persistence of contrast medium in
      the bilateral occipital lobes and part of the left frontal lobe. Repeat
      angiography showed no evidence of embolism. Single photon emission computed
      tomography obtained the next day showed decreased perfusion in the bilateral
      occipital lobes. Magnetic resonance imaging on the third day showed multiple
      lesions in the bilateral occipital lobes. Her vision was restored gradually.
      Transient cortical blindness may be associated with osmotic disruption of the
      blood-brain barrier in the bilateral occipital lobes. Endovascular neurosurgeons
      must be aware of this rare complication.

PMID- 15508350
TI  - Surgically treated aneurysm of the trunk of the persistent primitive trigeminal
      artery--case report.
AB  - A 62-year-old man presented with a very rare cerebral aneurysm arising from the
      trunk of the persistent primitive trigeminal artery (PPTA) manifesting as
      subarachnoid hemorrhage. Angiography showed a saccular aneurysm at the curved mid
      section of the trunk of the left PPTA of the adult type. The patient underwent
      surgery via the left subtemporal approach, and the aneurysm was successfully
      eliminated by clipping without sequelae. Aneurysm formation at this point was
      probably due to hemodynamic stress. The perforating arteries from the PPTA may be
      important in supply of the hindbrain, so PPTA patency should be preserved if
      possible.

PMID- 15508351
TI  - Large supratentorial ectopic ependymoma with massive calcification and cyst
      formation--case report.
AB  - A 6-year-old boy presented with a large supratentorial ependymoma with massive
      calcification and central cyst formation manifesting as generalized convulsion
      and right hemiparesis. Computed tomography and magnetic resonance imaging showed
      a large, poorly enhanced, left frontal mass with massive calcification and a
      central cyst. Angiography revealed no extracranial blood supply to the tumor,
      which was supplied by branches of the left middle cerebral artery. The patient
      underwent total resection of the tumor, which was located in the parenchyma with
      no dural attachment. The tumor was clearly demarcated and dissected subpially
      from the surrounding brain parenchyma. The surgical findings suggested no
      relationship with the lateral ventricular system. Histological examination of the
      tumor demonstrated perivascular pseudorosette formation and mitosis with massive
      calcification, and immunocytochemical reactivity for glial fibrillary acidic
      protein and epithelial membrane antigen, but not synaptophysin. These findings
      were compatible with ependymoma, World Health Organization grade 2. Postoperative
      magnetic resonance imaging clearly showed that the tumor was located in the
      intradural, intraaxial space with no relationship to the ventricles.

PMID- 15508352
TI  - Improvement of visual acuity caused by opticochiasmal astrocytoma after treatment
      for associated hydrocephalus--case report.
AB  - A 33-year-old male presented with syncopal attacks. He had a history of slowly
      progressive deterioration of visual acuity in both eyes. His visual deterioration
      began in the left eye at age 12 years and in the right eye at age 20 years. His
      left eye was completely blind by age 33 years. He had received no prior treatment
      for these visual disturbances. Magnetic resonance (MR) imaging on admission
      showed a large tumor with inhomogeneous intensity occupying the bilateral optic
      canals and orbital cavities, with extension to parasellar region. Arachnoid cysts
      were found in the left middle fossa and supracerebellar space, which had caused
      herniation of the cerebellar tonsils to the foramen magnum. Open biopsy and
      histology verified that the tumor was pilocytic astrocytoma. Arachnoid cysts
      associated with the hydrocephalus were treated with a ventriculoperitoneal shunt.
      Seven years after surgery, visual acuity of the right eye had improved although
      the left eye remained blind. Follow-up MR imaging demonstrated marked reduction
      in size of the ventricles and arachnoid cysts, but the tumor size did not change.
      This case illustrates the benign nature of low-grade glioma in this region in
      spite of the large size and long history. Deterioration of visual acuity may be
      reversible in some cases of opticochiasmal astrocytoma. In our case, the
      improvement in visual acuity probably resulted from growth arrest of the tumor
      and improvement in the dynamics of cerebrospinal fluid flow.

PMID- 15508353
TI  - Isolated third and fourth ventricles associated with neurosarcoidosis
      successfully treated by neuroendoscopy--case report.
AB  - A 48-year-old woman presented with a unique case of isolated third and fourth
      ventricles associated with neurosarcoidosis, manifesting as upward gaze palsy.
      She had a past history of surgery for intracranial sarcoid granuloma 10 years
      previously and placement of a ventriculoperitoneal shunt 3 years later. Magnetic
      resonance imaging revealed isolated third and fourth ventricles. Endoscopic
      plasty of the right foramen of Monro, fenestration of the septum pellucidum, and
      revision of the ventriculoperitoneal shunt were performed. Postoperatively the
      size of the third and fourth ventricles was reduced, and the upward gaze palsy
      resolved. Endoscopic treatment is less invasive and effective for the treatment
      of multiple septum formation in the ventricular system.

PMID- 15508354
TI  - Cystic tuberculomas of the brain--two case reports.
AB  - A 19-year-old male presented with raised intracranial pressure and a peripherally
      enhanced multinodular lesion with a large subjacent cyst in the right medial
      frontal lobe. Surgery revealed a solid tuberculoma and an underlying cyst lined
      with normal brain tissue. A 22-year-old male with a history of tuberculous
      meningitis and hydrocephalus presented with an exophytic brain stem and a left
      temporal tuberculoma, which were excised in two stages. The temporal tuberculoma
      had a peripherally located cyst that was lined with tuberculous tissue.
      Intracranial tuberculomas are an important part of the differential diagnosis
      where tuberculosis is endemic and in immunocompromised patients. Cystic
      tuberculomas are uncommon. The cysts may be centrally or peripherally
      intralesional, or either subdural and extralesional, or occur between the lesion
      and the brain. The type of cyst is important to recognize preoperatively, so that
      adequate precautions can be taken during the excision of these lesions.

PMID- 15508355
TI  - Development of a new irrigation sucker for microneurosurgery--technical note.
AB  - A new irrigation sucker (Delta Irrigation Sucker) was designed for
      microneurosurgery. The Delta Irrigation Sucker has a unique trigonal pyramid
      shape thumb piece, providing a very stable grip. Irrigation is achieved easily by
      pushing a small button just behind the pressure-regulating pore. Stable hold of
      the sucker and easy handling of the irrigation button enable irrigation without
      unsteadiness of the sucker. The Delta Irrigation Sucker is available in six
      sizes, with diameters from 1.5 mm to 4.0 mm at 0.5 mm intervals. Irrigation force
      is provided by a pressure bag, and a normal sterile transfusion set can be used
      as the irrigation circuit. The Delta Irrigation Sucker was used in 20 cases of
      clipping for ruptured cerebral aneurysm, five cases of tumor resection, and three
      cases of anterior clinoidectomy and opening of the internal auditory meatus.
      Subarachnoid clot was easily removed and the bleeding points were easily
      confirmed. Irrigation, controlled by natural finger movement, did not cause
      unsteadiness of the sucker.

PMID- 15508356
TI  - Contraceptive redesign: new progestins/new regimens.

PMID- 15508357
TI  - Intrauterine contraception: benefits to patients.

PMID- 15508358
TI  - Management strategies for PMS/PMDD.

PMID- 15508359
TI  - Do we really need family medicine research?

PMID- 15508360
TI  - Dr Olson's discovery and the meaning of "scientific".

PMID- 15508361
TI  - Creativity in clinical research is alive and well in Canadian family practice. Do
      we know it when we see it?

PMID- 15508362
TI  - Third year in family medicine: headed for disaster?

PMID- 15508363
TI  - Third year in family medicine: headed for disaster?

PMID- 15508364
TI  - Third year in family medicine: headed for disaster?

PMID- 15508365
TI  - Third year in family medicine: headed for disaster?

PMID- 15508366
TI  - Family physicians' increasing workload.

PMID- 15508367
TI  - Physician shortage: results are inconsistent.

PMID- 15508368
TI  - One step forward, one step back. The good and the bad of office visits.

PMID- 15508369
TI  - Is a fetus a non-consenting patient?
AB  - QUESTION: In the 1960s, Dr Cameron, a Montreal, Que, psychiatrist, experimented
      with drug-induced sleep and electroconvulsive therapy for psychiatric patients,
      believing that this method "wipes them clean of harmful memories." In 1992 the
      government of Canada settled lawsuits by former patients of Dr Cameron, awarding
      them large payments. The government rejected a similar claim by Lloyd Schrier,
      whose mother had been treated by Dr Cameron while she was carrying Lloyd, arguing
      that Lloyd was not Cameron's patient. Or was he? ANSWER: The fetus was exposed to
      the medications taken by his mother, (eg, barbiturates) and thus qualifies as an
      unconsenting patient.

PMID- 15508370
TI  - Discussing emergency contraception.

PMID- 15508371
TI  - Relief of ischemic leg pain with intermittent positive pressure.

PMID- 15508372
TI  - New drugs.

PMID- 15508373
TI  - Lifestyle management for type 2 diabetes. Are family physicians ready and
      willing?
AB  - OBJECTIVE: To determine practices and perceptions of family physicians regarding
      lifestyle interventions to prevent and manage type 2 diabetes (T2D). DESIGN:
      Confidential mailed survey. SETTING: Canadian family practices. PARTICIPANTS:
      Random, stratified sample of 1499 respondents to the 2001 National Family
      Physician Workforce Survey. MAIN OUTCOME MEASURES: Physicians' self-reported
      practice patterns and perceptions of lifestyle counseling for patients at risk
      for, and diagnosed with, T2D. RESULTS: Response rate was 53% (749/1410).
      Respondents frequently asked patients at risk for, or diagnosed with, T2D about
      physical activity and weight loss, but far fewer provided written advice,
      particularly about physical activity. Respondents thought counseling with such
      interventions as generic patient handouts was preferable to more intensive
      lifestyle management strategies, such as appointments to provide stage-matched
      counseling on physical activity. Most respondents thought family physicians
      should perform lifestyle interventions but realized they are confounded by such
      barriers as patients' lack of interest and limited referral resources.
      CONCLUSION: Family physicians keen to implement lifestyle interventions for T2D
      are hampered by barriers and use of ineffective strategies.

PMID- 15508374
TI  - Anticoagulation in atrial fibrillation. Is there a gap in care for ambulatory
      patients?
AB  - OBJECTIVE: Atrial fibrillation (AF) substantially increases risk of stroke.
      Evidence suggests that anticoagulation to reduce risk is underused (a "care
      gap"). Our objectives were to clarify measures of this gap in care by including
      data from family physicians and to determine why eligible patients were not
      receiving anticoagulation therapy. DESIGN: Telephone survey of family physicians
      regarding specific patients in their practices. SETTING: Nova Scotia.
      PARTICIPANTS: Ambulatory AF patients not taking warfarin who had risk factors
      that made anticoagulation appropriate. MAIN OUTCOME MEASURES: Proportion of
      patients removed from the care gap; reasons given for not giving the remainder
      anticoagulants. RESULTS: Half the patients thought to be in the care gap had
      previously unknown contraindications to anticoagulation, lacked a clear
      indication for anticoagulation, or were taking warfarin. Patients' refusal and
      anticipated problems with compliance and monitoring were among the reasons for
      not giving patients anticoagulants. CONCLUSION: Adding data from primary care
      physicians significantly narrowed the care gap. Attention should focus on the
      remaining reasons for not giving eligible patients anticoagulants.

PMID- 15508375
TI  - Recruitment for a provincial asthma study. Participation of network and non
      network primary care physicians.

PMID- 15508376
TI  - Road map for family medicine's journey to research.

PMID- 15508377
TI  - Family doctors under seige.

PMID- 15508378
TI  - Rich before old?

PMID- 15508379
TI  - Service learning opportunities in biomedical engineering senior design projects.

PMID- 15508380
TI  - Conductive keratoplasty.

PMID- 15508381
TI  - Integrative science: place and future of the model-based information processing.

PMID- 15508382
TI  - Molecular imaging: opportunities and challenges for bioengineers. Why is
      molecular imaging receiving so much attention?

PMID- 15508383
TI  - Positron emission tomography in molecular imaging. Could the promise of
      personalized patient care be reaching fruition?

PMID- 15508384
TI  - PET-based reporter gene imaging. Assessment of endogenous molecular-genetic
      events.

PMID- 15508385
TI  - Molecular imaging with single photon emission computed tomography. How new
      tracers can be employed in the nuclear medicine clinic.

PMID- 15508386
TI  - Near infrared optical applications in molecular imaging. Earlier, more accurate
      assessment of disease presence, disease course, and efficacy of disease
      treatment.

PMID- 15508387
TI  - A new beginning for human health.

PMID- 15508388
TI  - Optimization of industrial bacterial strains via mutation analysis: a high
      throughput DNA sequencing and bioinformatic approach.

PMID- 15508389
TI  - Follow the money.

PMID- 15508390
TI  - Security: a new clinical engineering paradigm.

PMID- 15508391
TI  - What is in the QSR/GMP?

PMID- 15508392
TI  - Latex allergy.

PMID- 15508394
TI  - Cochrane review--anal fissure.

PMID- 15508393
TI  - Speaking out for first assistants.

PMID- 15508395
TI  - I stuffed their mouths with gold.

PMID- 15508397
TI  - NATN speciality conference. Part two.

PMID- 15508396
TI  - New ways of working in anaesthesia.
AB  - Change and the NHS are synonymous; it is inevitable that new ways of working are
      explored to ensure an effective service. This article explores the possibility of
      using nonmedically trained anaesthetists in the operating theatre. It examines a
      current pilot being undertaken by the NHS Changing Workforce Programme (DoH
      2002a) and discusses how much impact this is likely to have in theatre.

PMID- 15508399
TI  - Developing the first assistant course at the Countess of Chester Hospital.
AB  - First assistant or advanced scrub practitioner roles have been undertaken by
      nurses since Florence Nightingale. Recently, theatre practitioners have
      undertaken this role as a matter of course, regardless of skill level. The
      Countess of Chester Hospital Theatres has produced the IS3 110 operating theatre
      first assistant module at level three. This runs alongside an in-house pathway of
      rapid evaluation of competence. Both are undertaken as work-based learning.

PMID- 15508398
TI  - Herbs: where's the harm?
AB  - The increased use of complementary and alternative medicine within our society
      requires us as professionals to educate our patients and ourselves as to the
      potential risks of taking herbs and vitamins. Herbs may be natural, but natural
      does not always equate to safe, and so this article provides a review of the
      literature and potential risks that herbs pose to surgery. Therefore we should
      encourage patients and health professionals alike to consider herbs as natural
      drugs and treat accordingly.

PMID- 15508400
TI  - The hazards of diathermy plume. Part 1. The literature search.
AB  - Laser and electrocautery devices used during surgery produce smoky emissions that
      may contain vapours and particulate aerosols, which can have a chemical and
      biological impact on those exposed. A group of theatre staff and specialist
      nurses at Rotherham District General Hospital got together to draw up a risk
      assessment into the possible occupational exposure of theatre staff, with a view
      to eliminating or controlling these hazards as far as possible.

PMID- 15508401
TI  - [Experiences in surgical management of acute arterial occlusions of the lower
      limb in the course of 20 years].
AB  - INTRODUCTION: In Hungary surgeons perform every year more then 2000 operations
      for treatment of acute arterial occlusion. Because of the advanced age and poor
      general condition of these patients, the postoperative mortality and complication
      rate is considerable. AIM: Authors analyzed changes in the etiology and therapy
      of acute arterial occlusions of lower limb in the last 20 years in a
      retrospective study. PATIENTS AND METHODS: 563 patients were operated on with
      acute arterial occlusion of lower extremities from 1983 to 2002 by the authors.
      Patients with vascular surgery in their history were excluded from this study.
      Student's two-samples "t"-test, chi2- and Fisher's exact test were used in
      Statistica 6.0 for statistics. RESULTS: Period of 1983-1992 compared to period of
      1993-2002 they found increased rate of occlusions caused by thrombosis (35 vs.
      46%, p < 0.01) and increased number of acute vascular reconstructions performed
      with indication of acute thrombosis (17.6 vs. 47.0%, p < 0.001). Mortality was
      higher in patients operated with embolism than in patients with thrombosis (17.7
      vs. 11.6%, p < 0.01), but the ratio of postoperative amputation following
      embolectomy was lower than following thrombectomy (5.0 vs. 16.0%, p < 0.01).
      Thrombectomy itself could solve the occlusion caused by thrombosis only in 50% of
      cases. Results of reoperations following unsuccessful thrombectomies are very
      poor. Amputation was necessary in 6.8% (in 5 cases of 74 patients) after primary
      reconstructions, but in 28.6% (in 14 cases of 49 patients) after reoperations.
      There was no significant difference in postoperative mortality among primary
      reconstructed, reoperated and conservatively treated groups. CONCLUSIONS: By
      author's experience, in cases of acute occlusion caused by thrombosis as a
      complication of chronic obliterative arterial disease, basic cause of occlusion
      should be searched for and--if conditions are suitable--procedure should be
      extend to vascular reconstruction.

PMID- 15508402
TI  - [Indication for local intra-arterial chemotherapy in malignant liver tumors].
AB  - The possibilities for curative treatment of malignant hepatic tumours are:
      surgical resection, percutaneous local ablation using radiofrequency or laser. In
      cases of advanced tumors we can choose the vascular ablation including
      chemoperfusion and chemoembolization and feeding artery occlusion. Combinations
      of surgical resection or percutaneous ablation with local and systemic
      chemotherapy provide a better result for patients.

PMID- 15508403
TI  - [Treatment options of bone defects in revision of total knee replacement].
AB  - Total condylar knee replacement presently has more than 10 years of history in
      Hungary. Besides a large number of routine primary implantations, the number of
      exchange arthroplasties performed due to aseptic loosening is continuously
      growing as well. One of the most significant difficulties of revision
      interventions is the management of bone defects. OBJECTIVE: Aim of present study
      is to describe the treatment options of bone deficiencies found during knee
      arthroplasties. Indication criteria of different methods are introduced together
      with the results of revision operations dealing with bone defects in the authors'
      patient sample. METHOD: Between 1995 and 2001, 35 revision total knee
      replacements have been performed at the authors' institute where significant bone
      defects had to be dealt with. Because of aseptic loosening, unior bicondylar
      implant revision has been carried out in 24 cases and total condylar prosthesis
      revision in 11 cases. With 14 patients autologous bone, in 7 cases allogenic
      cancellous bone and in two cases structural allografts have been used. Metal
      augmentation of the prosthesis in itself was applied in 4 patients, in 8 further
      patients in combination with bone grafts. RESULTS: During physical and
      radiological control examination of 31 knees in average 3 years after the
      operation, authors found good clinical results in all cases except one. Bone
      grafts showed good remodeling, and the implants were all fixed well on the
      control radiographs except of the one failed case. With this patient, collapse of
      the structural allograft used for reconstruction of a large medial tibial defect
      was evident and the tibial component became loose. CONCLUSIONS: Based on
      international literature data and their own experiences, authors conclude that
      aseptic loosening of total knee endoprostheses can be managed with good results
      even if it is combined with massive bone loss. For a successful revision, an
      appropriate technical background, personal skills and a well-functioning bone
      bank is unavoidable. For the management of tibial defects, authors highly
      recommend the usage of long stem extensions.

PMID- 15508404
TI  - [Physiologic and pathologic role of iron in the human body. Iron deficiency
      anemia in newborn babies].
AB  - Iron is one of the most important essential metal ions of which significance is
      well known for ages. This element is a key moiety of several enzymes in iron
      containing heme or nonheme form and transfer and storage protein, hemoglobin and
      myoglobin. Several membrane carriers of iron have already been identified. The
      redox state of iron is determined by xanthine oxidase, cytochromes and Hp or
      ceruloplasmin and ferroxidase activity of apo-ferritin, respectively. Some
      vitamins (C, B2-, B3-, B6-, B12) play also a role in the metabolism of iron. The
      iron content of cells of the organs is well regulated by the iron homeostasis.
      Iron has a significant role in the immune system by producing oxygen containing
      free radicals. Anaemia induced by iron deficiency may cause a challenge concerns
      for pregnant women, babies and adolescent, primarily.

PMID- 15508405
TI  - [Treatment of chronic hepatitis B].

PMID- 15508406
TI  - [Protection against epidemic in the hinterland during WW1--observation wards
      ("barrack hospitals")].

PMID- 15508407
TI  - [Mor Szalardy (1851-1914)].

PMID- 15508408
TI  - [Contribution to the discussion about antihypertensive drugs].

PMID- 15508409
TI  - Immune system parameters in children of Central and Eastern Europe: the CESAR
      study.
AB  - OBJECTIVE: of this paper is to compare observed values of immune parameters
      obtained in the CESAR study (The Central Europe Study of Air Pollution and
      Respiratory Health, funded by EC PHARE program) with ranges derived from other
      large population-based studies. STUDY DESIGN: Data were collected in healthy
      school children aged 9-11 years, in 6 countries: Bulgaria, the Czech Republic,
      Hungary, Poland, Romania and the Slovak Republic with the same standard approach
      in 1996. Random samples of 85 children per country, from 19 communities were
      selected from children having completed the health questionnaire, in total 495
      children were analyzed. Lymphocyte subsets were determined by two-colour flow
      cytometric immunophenotyping using the lysed whole blood method (Becton
      Dickinson). For determination of immunoglobulin concentration in sera
      nephelometric method (Behring Nephelometer system) was used. RESULTS: Medians,
      (5th-95th percentiles) of the lymphocyte subsets absolute count (x 10(9)/l) were
      as follows: CD19+ B cells 0.36 (0.13-0.66), total CD3+ T cells 1.74 (0.98-2.90),
      CD3+CD4+ helper-inducer T cells 0.95 (0.47-1.78), CD3+CD8+ suppressor/cytotoxic T
      cells 0.71 (0.38-1.22), CD3-CD16+56+ NK cells 0.36 (0.14-0.78), and for
      CD3+CD4+/CD3+CD8+ ratio 1.4 (0.8-2.4). Medians, (5th-95th percentiles) of
      percentages of lymphocyte subpopulations (%) were as follows: CD19+ B 13 (7-22),
      CD3+ T 70 (59-80), CD3+CD4+ T 38 (27-48), CD3+CD8+ T 28 (20-39), CD3-CD16+56+ NK
      cells 14 (6-27). Medians, (2.5th-97.5th percentiles) of the total immunoglobulin
      [g/l] were 11.7 (7.4-18.2) for IgG, 1.2 (0.5-2.5) for IgM, and 1.5 (0.5-3.4) for
      IgA. Based on the aspects of the size of the CESAR immune biomarker study and on
      the use of the standardized protocols we recommend to use the reference ranges on
      lymphocyte subsets and immunoglobulin in Europe as provided by this study.

PMID- 15508410
TI  - The 6th nationwide anthropological survey of children and adolescents in the
      Czech Republic in 2001.
AB  - The 6th nationwide anthropological survey (NAS) of children and adolescents was
      carried out in the Czech Republic in 2001 to continue the series of surveys
      repeated at 10-year intervals since 1951 (with the participation of the Slovak
      Republic up to 1991). The major objective was to find out the following body
      measurements of children and adolescents: body height and weight, and head, arm,
      waist and hip circumferences. Questionnaires were used to find out the body
      measurements of parents (body height and weight) and some socio-economic
      characteristics of the child's family (number of siblings, education of parents,
      breast feeding duration, birth weight and length, child's physical activities, TV
      watching time, computer gaming time, etc.). A school children questionnaire
      focused on eating habits was also part of the survey in 2001. A total of 59,000
      children aged 0.00 to 18.99 years, i.e. about 3% of the population of the same
      age range, were enrolled in the survey in 2001. The results obtained presented in
      diagrammatic and tabular forms are reference standards for monitoring growth of
      the Czech children and adolescents from birth to the age of 19 years. The survey
      revealed a substantial slowdown in the long-term trend in body height increase
      for both boys and girls. The most marked increase in the mean body height is
      currently recorded in boys at the prepubescent age while the pubescent girls show
      a practically zero increase for this parameter. A more marked increase in body
      height at the adult age is not expected any more, but the increase in body height
      and weight at the prepubescent age is likely to continue for some time. The 6th
      NAS showed a marked slow down to a stop in the trend in the mean body weight
      increase. No increase in the mean body weight has been recorded in pubescent
      girls since the 1970's and in pubescent and postpubescent boys since 1991.
      Nevertheless, the younger age groups, namely those of preschool and primary
      school children, continue to show increase in the mean body weight. The secular
      trend in body weight has been less pronounced compared to that in body height.
      The rates of overweight and obese children (as assessed by body mass index, BMI)
      have risen in most age groups of school children compared to those reported in
      1991. In contrast, a slight decrease in the rate of overweight children can be
      seen in boys starting from the age of 16 years and in girls starting from the age
      of 13 years. The obesity prevalence rate is significantly higher in boys than
      girls. Statistical analysis confirmed a correlation between the BMI values in
      children and education of parents (the higher the education, the lower the rate
      of overweight children) and between the BMI values and the population size of the
      community where the child lives (the higher the population, the lower the
      prevalence rates of overweight and obesity). Single children suffer more
      frequently from overweight and obesity than those with siblings.

PMID- 15508411
TI  - The results of dietary advice on lipoprotein levels among patients attending for
      lipid-lowering drugs.
AB  - The aim of this study was to evaluate the changes in fasting lipoproteins levels
      before and after a dietary advice among the patients attending for a lipid
      lowering treatment. In total 286 patients attending for reimbursement of a lipid
      lowering drug were recorded at two regional health insurance offices. Lipid
      levels measured at least three months after the dietary advice were compared with
      those before the dietary advice. The mean age of the included patients was 61
      years. The average fasting total cholesterol (TC) was 7.4 mmol/l before the
      dietary advice as well as after the dietary advice. Fasting TC did not decrease
      with the dietary advice in 51% of the included patients. In the logistic
      regression not one of the studied factors was correlated with a successful
      dietary advice. Half of the patients receiving lipid-lowering drugs in Belgium
      were not able to decrease their TC with dietary advice before the initiation of
      the treatment.

PMID- 15508412
TI  - Glycemic and insulinemic responses to six cereal products in healthy adults.
AB  - Glycemic index (GI) and insulin index (II) scores of six cereal-based foods
      (biscuits and shortbreads) were determined and the relationship between the
      glycemic and insulin responses of the foods was examined. The study was conducted
      using recommended by FAO/WHO methodology using glucose as a standard food. We
      obtained a range of GI scores from 49 to 68% and II scores from 51 to 75%. The
      test foods' blood insulin responses were in parallel to their glycemic responses
      although in every case the level of II was higher than the level of GI. The
      foods' II scores were closely related to their GI scores (r=0.80).

PMID- 15508413
TI  - Molecular epidemiology of tuberculosis in Prague and South Moravia, Czech
      Republic: genetic analysis of Mycobacterium tuberculosis isolates by IS6110-RFLP
      fingerprinting and spoligotyping.
AB  - OBJECTIVES: To genetically characterize and compare Mycobacterium tuberculosis
      isolates among culture-confirmed TB cases in two regions in the Czech Republic in
      1998. METHODS: Consecutive M. tuberculosis isolates from 111 TB patients in
      Prague and 120 patients in the South Moravia region were genotyped using the
      standardized IS6110 Southern blot hybridization method and by spoligotyping.
      RESULTS: Eighty of the Prague patients (72.1%) had isolates with unique RFLP
      patterns, while 31 (27.9%) had isolates which belonged to 10 clusters. Seventy
      eight (64.7%) of the South Moravia strains displayed unique RFLP pattern and 42
      (35.3%) were assigned into 15 clusters. The spoligotype profiles previously
      identified in the U.S. were found in 69 (33%) samples and newly identified Czech
      spoligotypes in 24 (11.4%) of the total number of examined strains. CONCLUSIONS:
      The present population-based molecular epidemiological study performed in two
      regions of the Czech Republic in 1998 demonstrated the distribution of individual
      genotypes as well as clustered strains of M. tuberculosis isolated from TB
      patients, and confirmed the similarity between the Czech strain collection and
      the European Community TB Database, that includes countries with low TB rate. The
      sporadic import of TB cases from foreign countries and recent transmission events
      probably do not play significant roles in the epidemiological situation in the
      Czech Republic.

PMID- 15508414
TI  - Prevalence of Borrelia burgdorferi sensu lato genospecies in host-seeking Ixodes
      ricinus ticks in selected South Bohemian locations (Czech Republic).
AB  - In selected localities of Ceske Budejovice and Cesky, Krumlov districts, well
      known by stable high incidence of tick-borne encephalitis (TBE) human cases but
      with low incidence of Lyme borreliosis, monitoring of Borrelia burgdorferi sensu
      lato (s.l.) in Ixodes ricinus ticks was performed. Research was also aimed at the
      spread of I. ricinus to mountain areas of this region (National Park Sumava), as
      well as at investigating this tick for B. burgdorferi s.l. genospecies and TBE
      virus infection. Altogether 498 nymphs, 88 females and 11 males of I. ricinus
      from lower locations and 58 nymphs from mountain locations (760-1080 m above sea
      level) were tested by polymerase chain reaction. In lower locations total
      prevalence of Borrelia burgdorferi s.l. in Ixodes ricinus ticks was 35%. Single
      infection of Borrelia afzelii, B. garinii and B. burgdorferi sensu stricto (s.s.)
      was found in 59, 50 and 63 ticks, respectively (i.e. in 12.8, 11.2 and 14.1%).
      Double infection was found in 42 ticks (6.0%) and triple infection in three ticks
      (0.4%). The high frequency of B. burgdorferi s.s. exceeds the as yet reported
      occurrence in Central Europe. These circumstances are discussed. In mountain
      locations B. afzelii was found in five ticks, that including two co-infection
      with B. garinii, in elevations of 762 m and 1024 m above sea level, respectively.
      This fact signals a real danger of human infections in a region that was
      previously deemed to be without risk. Moreover, this region is more and more the
      target destination of tourist activities. The results also suggest that the
      penetration of infection can be rapid and formation and establishment of natural
      focus of Lyme borreliosis might be rather quick.

PMID- 15508415
TI  - Influence of prenatal and postnatal exposure to passive smoking on infants'
      health during the first six months of their life.
AB  - On the Czech set of European Longitudinal Study of Pregnancy and Childhood
      (ELSPAC), we tried to verify whether it is possible to confirm the results of
      foreign studies which found out that the both prenatal and postnatal exposure of
      newborns to chemicals on cigarette smoke could influence the newborns' morbidity
      in the first six months of their life. Mothers, who served as sources of data
      about their smoking behaviour during the pregnancy and after the birth as well as
      information about the health status of the children after the birth (N=3,871)
      were divided into four groups: 1. women who never smoked (74.3%), 2. women who
      stopped smoking in pregnancy and started to smoke after delivery (18.3%), 3.
      women who smoked both during pregnancy and after delivery (7.2%), 4. women who
      smoked during pregnancy and stopped after delivery. Unfortunatelly, the last
      group was very small (only seven mothers) and did not allow assessment of
      exclusively prenatal exposition. Sucklings from Czech ELSPAC set exposed to
      chemicals in cigarette smoke either only after the birth or also during the
      prenatal period, showed significantly higher occurence of different symptoms of
      respiratory tract damages and their complications (like otitis media) when
      compared to children of non smoking mothers. Due to illnesses during the first
      six months after the birth, their parents had to look more often for the
      consultations of physician, including hospitalization. Our results, as well as
      results of foreign studies, confirm, that smoking of mothers during the pregnancy
      and after the birth represents significant risk for the first months of life.
      Illnesses of children in this early period can cause longitudinal consequences
      which emerge during the childhood as well as in adulthood. They also represent a
      strong stressogenic factor. Children's health consequences of exposure to
      cigarette smoke request very often intensive and expensive care within health
      system. Our results are the same as those of foreign studies and confirm that
      both prenatal and postnatal exposure to chemicals of cigarette smoke is
      significant risk factor which negatively influences the health status on the
      early periods life.

PMID- 15508416
TI  - Structural problems in the German hospital system.
AB  - The German health care system has been based on the Hospital Financing Act, which
      the German government introduced in 1972. According to that, the federal states
      plan hospitals and make investments. The health insurance funds finance the
      operating costs. But now the Hospital Financing Act is obsolete, because both the
      health insurance funds and the federal states are in financial trouble and try to
      avoid the costs, which are nevertheless rising. In order to freeze costs, the
      legislators have introduced a new remuneration system, called DRGs (Diagnosis
      Related Groups), which will be mandatory from 2007 onwards. In this system, the
      treatment provided will be coded and remunerated on the basis of the primary
      diagnosis. Periods of hospitalisation and different remuneration systems will no
      longer be relevant. Transparency and quality will thus be promoted, and the
      upshot will be more competition among the hospitals. Hospitals that cannot meet
      quality standards will lose patients and will ultimately have to close. Other
      participants in the health care system, such as, for example, nursing staff,
      physicians, pharmacies, rehabilitaion centres and patients, will also be
      concerned in many ways. The consequences of the DRGs for the health care system,
      its future development and possible alternatives are discussed in this article.

PMID- 15508417
TI  - Life cycle approach to child and adolescent health.
AB  - Young people are our human capital for the future, therefore child and adolescent
      health has attracted considerable political and professional attention in recent
      years. Health is indivisible, requires holistic approach throughout the
      individual's life. Healthy outcome at one point in the life cycle, provides a
      positive determinant for health elsewhere in the cycle. Health and development of
      the 0-19 age group links intimately, at both ends of the range, with reproductive
      health. Health during childhood is in part determined by the health of the
      mother, and affected also by factors such as the nutrition of adolescent girls
      and the avoidance of early pregnancy. These factors, in turn, are influenced by
      healthy growth and development in childhood. The paper presents main
      environmental and socio-cultural challenges for each of the stages of child and
      adolescent life. Main challenge described are: unsafe abortion, malnutrition,
      anaemia, malformations, and infections during pregnancy; low birth weight,
      asphyxia, hypothermia, infection, failure to initiate early and full
      breastfeeding in the neonatal period; poor nutrition, growth and development,
      frequent illnesses, injury, abuse and neglect in the early childhood; poor
      nutrition, growth and development, injury, abuse, neglect, and helminth
      infections in the early school age; poor nutrition, poor development, chronic
      conditions, mental disorders, injury, drug abuse, and violence in the
      adolescence. Both, prevention of ill health and care for illnesses are important
      at all times but the balance between them shifts over time during the childhood
      and adolescence. Main actions needed to meet the child and adolescent needs are
      presented as well.

PMID- 15508418
TI  - Applied research is as important as ever.

PMID- 15508419
TI  - Diffusive boundary layer development above a sediment-water interface.
AB  - A model to estimate the entry length to a fully developed diffusive boundary
      layer above a sediment bed, such as those found in lakes, reservoirs, rivers, and
      estuaries, is presented. The model is used to determine how the length of a
      sediment bed in mass-transfer experiments influences the measured vertical
      diffusive flux at the sediment-water interface. A nondimensional local mass flux
      is introduced in the form of a Sherwood number (Sh) and expressed as a function
      of both the distance from the leading edge of the sediment bed (x) and the
      Schmidt number (Sc). Similarly, a mean Sherwood number (Sh(ave)) for a sediment
      bed of length (L) is introduced. The diffusive boundary layer grows with
      distance, and its thickness depends on the Schmidt number (i.e., the diffusive
      boundary layer gets thicker and develops more quickly as the Schmidt number
      decreases). For Schmidt numbers greater than or equal to 100, the diffusive
      boundary layer begins to develop slowly but is fully developed when the
      nondimensional horizontal coordinate (x+) is approximately 1000. The Sherwood
      number is largest (i.e., infinity) near the leading edge of the sediment bed
      (i.e., at x = 0), decreases as the distance from the bed increases, and, finally,
      approaches a constant value for a fully developed diffusive boundary layer
      (Sh(infinity)). In this paper, the distance to a fully developed diffusive
      boundary layer (L99) and the required length of a sediment bed are related
      explicitly to Sc, sheer velocity (U*), and the relative errors of local or
      average Sherwood numbers (Sh or Sh(ave), respectively) against the Sherwood
      number for the fully developed diffusive boundary layer (Sh(infinity)). The
      lengths L99 and L decrease as the Schmidt number increases and become independent
      of the Schmidt number when Sc is greater than 1000. A longer sediment bed is
      needed when the shear velocity or the Schmidt number is small (e.g., L99 and L
      approximately 1.0 m and 8.0 m, respectively, for Sc = 500, U* = 0.1 cm/s, and a
      3% acceptable error). Experimental studies may not be able to meet these
      requirements and an adjustment of measured mass-transfer rates at a sediment
      water interface may be necessary. The magnitude of that adjustment is up to 50%.
      Its dependence on the Schmidt number, shear velocity, and bed length is given in
      this paper.

PMID- 15508420
TI  - Chemical oxygen demand reduction of various wastewater types using magnetic field
      assisted fenton reaction.
AB  - Constant magnetic field (CMF) was investigated for its potential to intensify
      chemical oxygen demand (COD) removal in wastewater when applied with a
      generalized Fenton reaction. Various types of industrial and domestic wastewater
      were tested in the experiment. A significant dependence was observed between the
      wastewater type, dose of reacting substances, time of exposure to CMF,
      effectiveness of COD removal, and the rate of the advanced oxidation process. The
      use of CMF resulted in the improvement of the treatment process; however, the
      efficiency depended to a great extent on the type of wastewater and
      characteristics of the contained organic matter. Domestic wastewater seemed to be
      most amenable to the applied treatment (82% COD reduction). The least reduction
      in COD occurred for wood industry wastewater. In the analyzed wastewater, intense
      oxidation was observed during the first 60 minutes of the process. Longer
      reaction time did not increase COD reduction, with the exception of wood industry
      wastewater. The experiment revealed the possibility of applying smaller doses of
      the Fenton's reagent, thereby keeping up unchanged treatment efficiency, provided
      that CMFs are applied.

PMID- 15508421
TI  - Measurement of biosolids compost odor emissions from a windrow, static pile, and
      biofilter.
AB  - A pilot study was conducted to compare odor emissions from a windrow process and
      an aerated static pile and to determine the odor reduction efficiency of a pilot
      two-phase biofilter for odor control of biosolids composting. Chemical compounds
      identified as responsible for odors from biosolids composting include ammonia,
      dimethyl disulfide, carbon disulfide, formic acid, acetic acid, and sulfur
      dioxide (or carbonyl sulfide). Aeration was found to reduce the concentration of
      ammonia, formic acid, and acetic acid by 72, 57, and 11%, respectively, compared
      with a nearby windrow, while dimethyl sulfide, carbon disulfide, and sulfur
      dioxide (or carbonyl sulfide) concentrations were below detection limits. Using
      dilution-to-threshold olfactometry, aeration followed by biofiltration was found
      to reduce the odor from biosolids composting by 98%. Biofiltration also altered
      the character of odor emissions from biosolids composting, producing a less
      offensive odor with an earthy character. Biofiltration was found to reduce the
      concentration of ammonia, dimethyl disulfide, carbon disulfide, formic acid,
      acetic acid, and sulfur dioxide (or carbonyl sulfide) by 99, 90, 32, 100, 34, and
      100%, respectively. The concentrations of those odorants were estimated to be
      3700, 110000, 26,37,5, and 1.2 times reported human detection limits before the
      two-phase biofilter, respectively, and 42,9600,18,0,3, and 0 times human
      detection limits after the biofilter, respectively.

PMID- 15508422
TI  - N-nitrosodimethylamine: a disinfectant byproduct and its occurrence in
      wastewater.
AB  - This paper will provide wastewater treatment utility professionals with a
      comprehensive synthesis of information pertinent to N-nitrosodimethylamine (NDMA)
      so that plant operators can make informed and cost-effective decisions regarding
      appropriate management techniques. A suspect disinfection byproduct, NDMA is a
      potential carcinogen and is presently under scrutiny from the U.S. Environmental
      Protection Agency because it poses a threat to groundwaters from reclaimed
      wastewaters. Recognizing that the current state of knowledge pertaining to the
      occurrence and treatment of NDMA from wastewater treatment is in its infancy, the
      information presented in this paper is timely and will help utility professionals
      develop confidence toward controlling NDMA during wastewater treatment. Given the
      increased probability of the formation of NDMA using current wastewater treatment
      technologies and also in the complex matrices of the wastewaters subjected to UV
      treatment, the investigation of occurrence pathways and means of suppression of
      NDMA formation before and after treatment needs to be investigated. This paper
      also summarizes strategies to minimize exposure such as modifying treatment or
      instituting waste and agricultural management practices that minimize inorganic
      and organic nitrogen discharges to wastewaters.

PMID- 15508423
TI  - Effects of chlorination on the adhesion strength and deflocculation of activated
      sludge flocs.
AB  - A side effect of the application of chlorine for controlling filamentous bulking
      is deflocculation of floc-forming bacteria, which may cause unacceptable effluent
      deterioration depending on dosing. It was assumed that chlorine may adversely
      affect the adhesion ability of floc bacteria, promoting their erosion in shear
      flow. The effect of chlorination on the strength of activated sludge flocs was
      investigated. The adhesion-erosion (AE) model developed by Mikkelsen and Keiding
      was used to interpret results from deflocculation tests with varying shear and
      solids concentration. The AE model yields the adhesion enthalpy (deltaHG/R) of
      cells in sludge flocs and parameters from the model were used to quantify the
      sludge in terms of floc strength. Two activated sludges with different initial
      characteristics were studied. The resulting model parameters showed that the AE
      model was suitable for quantifying the bond energy of particles to the activated
      sludge exposed to chlorine. For one activated sludge, adhesion of cells was
      largely unaffected by the applied chlorine doses. A second sludge showed reduced
      adhesion strength with chlorine, leading to increasing deflocculation. The simple
      batch test and AE model proved valuable for assessing the effect of chlorination
      on the flocs in activated sludge. By use of these procedures, it is possible to
      determine acceptable chlorine dosing to avoid excessive deflocculation and
      effluent deterioration.

PMID- 15508424
TI  - Slaughterhouse wastewater treatment in a full-scale system with constructed
      wetlands.
AB  - This work evaluated the performance of a full-scale system with wetlands for
      slaughterhouse (abattoir) effluent treatment in the State of Hidalgo, Mexico. The
      treatment system consisted of a primary sedimentation tank, an anaerobic lagoon,
      and a constructed subsurface-flow wetland, in series. The wetland accounted for
      almost 30% of the removal of organic matter. In general, the treatment system
      achieved satisfactory pollutant removals, but the final effluent could not meet
      the Mexican environmental regulations for fecal coliform counts, five-day
      biochemical oxygen demand (BOD5), and total suspended solids (TSS). Overall,
      removal levels were 91%, 89%, and 85% for BOD5, chemical oxygen demand, and TSS,
      respectively. However, BOD5 in the final effluent (137 mg/L) was higher than the
      maximum level of 30 mg/L allowed by the regulatory agency. Although organic
      nitrogen removal levels were approximately 80%, the nitrogen persisted in
      oxidation state -3 as ammonia-nitrogen, the removal of which was only 9% in the
      wetland stage. On average, phosphorus removal was null, and, on occasion, the
      phosphorus concentration in the treated effluent was higher than that of the
      influent. Coliform reductions in the overall system were high (on the order of 5
      logs on average), whereas the coliform removal in the wetland was between 2 to
      3.5 logs. The treatment system was also effective at removing pathogens (Vibrio
      cholerae, Salmonella, and Shigella). Further laboratory tests with the wetland
      effluent suggest that post treatment in a sand filter stage followed by
      disinfection with sodium hypochlorite (NaOCl) could help meet the Mexican
      discharge regulations, particularly the criteria for coliforms and total BOD5.

PMID- 15508425
TI  - Case study I: application of the divalent cation bridging theory to improve
      biofloc properties and industrial activated sludge system performance-direct
      addition of divalent cations.
AB  - The objectives of this study were to examine the application of the divalent
      cation bridging theory (DCBT) to improve settling, dewatering, and effluent
      quality in pilot-scale reactors and a full-scale system treating an industrial
      wastewater. This was accomplished by lowering the monovalent-to-divalent (M/D)
      cation ratio by direct divalent cation addition. Research has shown that the M/D
      ratio is a potential indicator for settling and dewatering problems at wastewater
      treatment plants, and M/D ratios above 2 have been associated with poor settling,
      dewatering, and effluent quality. The M/D ratio of the wastewater in this study
      ranged from 6 to 20. The cations studied were calcium and magnesium. Results
      showed that the addition of calcium improved floc properties compared to control
      reactors with no calcium addition. The reductions in sludge volume index,
      effluent chemical oxygen demand (COD), and effluent total suspended solids (TSS)
      were approximately 35, 34, and 55%, respectively, when the M/D ratio was
      decreased to approximately 2:1. In addition, the cake solids from a belt filter
      press simulator increased by 72% and the optimum polymer dose required for
      conditioning was reduced by 70% in the reactor fed the highest calcium
      concentration when compared to control reactors with no calcium addition. The
      addition of calcium also decreased the negative effect of high filamentous
      organism numbers. In general, the addition of magnesium (Mg2+) had similar
      effects on effluent quality and dewatering properties, although some differences
      were measured. A full-scale test using calcium addition was performed.
      Measurements of effluent quality and floc properties were performed before,
      during, and after the calcium (Ca2+) addition period. The average M/D ratio
      during these periods was 6.2, 4.6, and 14.0, respectively. The addition of Ca2+
      decreased the effluent five-day biochemical oxygen demand, effluent TSS, and
      effluent COD. The increased Ca2+ concentration also improved dewatering measured
      by a decrease in specific resistance to filtration and capillary suction time.
      Overall, the addition of divalent cations to the pilot- and full-scale activated
      sludge systems improved floc properties and the data fit well with the DCBT.

PMID- 15508426
TI  - Case study II: application of the divalent cation bridging theory to improve
      biofloc properties and industrial activated sludge system performance-using
      alternatives to sodium-based chemicals.
AB  - The objective of this study was to investigate the application of the divalent
      cation bridging theory (DCBT) as a tool in the chemical selection process at an
      activated sludge plant to improve settling, dewatering, and effluent quality.
      According to the DCBT, to achieve improvements, the goal of chemical selection
      should be to reduce the ratio of monovalent-to-divalent (M/D) cations. A study
      was conducted to determine the effect of using magnesium hydroxide [Mg(OH)2] as
      an alternative to sodium hydroxide (NaOH) at a full-scale industrial wastewater
      treatment plant. Floc properties and treatment plant performance were measured
      for approximately one year during two periods of NaOH addition and Mg(OH)2
      addition. A cost analysis of plant operation during NaOH and Mg(OH)2 use was also
      performed. During NaOH addition, the M/D ratio was 48, while, during Mg(OH)2
      addition, this ratio was reduced to an average of approximately 0.1. During the
      Mg(OH)2 addition period, the sludge volume index, effluent total suspended
      solids, and effluent chemical oxygen demand were reduced by approximately 63, 31,
      and 50%, respectively, compared to the NaOH addition period. The alum and polymer
      dose used for clarification was reduced by approximately 50 and 60%,
      respectively, during Mg(OH)2 addition. The dewatering properties of the activated
      sludge improved dewatering as measured by decreased capillary suction time and
      specific resistance to filtration (SRF), along with an increase in cake solids
      from the SRF test. This corresponded to a reduction in the volume of solids
      thickened by centrifuges at the treatment plant, which reduced the disposal costs
      of solids. Considering the costs for chemicals and solids disposal, the annual
      cost of using Mg(OH)2 was approximately 30,000 dollars to 115,000 dollars less
      than using NaOH, depending on the pricing of NaOH. The results of this study
      confirm that the DCBT is a useful tool for assessing chemical-addition strategies
      and their potential effect on activated sludge performance.

PMID- 15508427
TI  - Laboratory-scale comparison of anaerobic-digestion alternatives.
AB  - Laboratory-scale digesters were used to perform side-by-side evaluations of
      alternative digestion systems including thermophilic-mesophilic-phased digestion
      (TPAD), acid/methane-phased digestion, mesophilic digestion, and the performance
      of the thermophilic stage of TPAD alone. Total detention times in the systems
      evaluated varied from 8 to 20 days. Temperatures in the mesophilic stage of TPAD
      were varied from 35 to 43.3 degrees C and temperatures in the thermophilic stage
      were varied from 55 to 58.9 degrees C. The purpose of the study was to evaluate
      volatile solids (VS) reduction and thickening properties of the different
      systems. Parameters evaluated included solids, volatile acids, gas production and
      quality, various chemical constituents of the sludge, and thickening properties
      using polymer and ferric chloride plus polymer. The TPAD systems were found
      capable of higher VS destruction at total detention times of 10 and 12.5 days
      compared to single-stage mesophilic or thermophilic digestion at 15 to 20 days. A
      laboratory-scale thickening test was performed to evaluate thickening properties.
      Based on obtaining 95% capture in the test, the polymer demand of mesophilic and
      acid-methane-phased digestion was the lowest. The TPAD system required
      approximately 180% of the dosage of the mesophilic sludge and thermophilic sludge
      required approximately 310% of the dosage. Temperatures of 40.5 and 43.3 degrees
      C in the mesophilic stage of TPAD were found to increase the polymer requirement
      and decrease the VS reduction of the TPAD system. Higher temperatures (above 56.1
      degrees C) and lower detention times (less than 15 days) in the thermophilic
      digesters seemed to result in problems with degradation of volatile acids,
      particularly propionic acid.

PMID- 15508428
TI  - Production of polyhydroxyalkanoate during treatment of low-phosphorus-content
      wastewater.
AB  - To evaluate whether poly-beta-hydroxyalkanoate (PHA) production and wastewater
      treatment could be combined in a single biological process, a bench-scale
      sequencing batch reactor was operated with sequential anaerobic and aerobic
      stages and removal of excess sludge at different stages of treatment. The reactor
      treated synthetic wastewater with a high organic and low nutrient content,
      simulating industrial wastewater. Chemical oxygen demand removal efficiency was
      more than 90% in all cases. Poly-beta-hydroxyalkanoate accumulation was
      significant, although it did not appear to be induced by oxygen limitations
      during the anaerobic stage. Sphaerotilus natans was apparently the dominant PHA
      accumulating organism at the end of each reactor run and corresponded to a PHA
      accumulation of 16 to 20% of the total dry cell mass. Before S. natans dominated
      the reactors, PHA accumulation was approximately 17% when biomass was removed at
      the end of the aerobic stage and 6.6% when sludge removal also occurred during
      the anaerobic stage.

PMID- 15508429
TI  - Substrates of human cytochromes P450 from families CYP1 and CYP2: analysis of
      enzyme selectivity and metabolism.
AB  - A compilation of information relating to substrate metabolism via human
      cytochromes P450 (CYP) from the CYP1 and CYP2 families is reported. The data
      presented include details of preferred sites of metabolism and Km values (usually
      for the expressed enzymes) for each reaction for selected substrates of CYP1A2,
      CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP2E1. Although other P450
      databases are available, they do not provide such information as is collated
      here, and which can prove useful for comparing P450 substrate characteristics.
      This information can be employed in analysing the structural requirements for
      human P450 enzyme selectivity and for establishing various rules regarding
      preferred site of metabolism for selective P450 substrates. For example, in most
      cases it would appear that there is a set number of intervening 'heavy' atoms
      (atoms other than hydrogen) between sites of metabolism and key hydrogen bond
      acceptors (or donors) for human P450 substrates, with the number of intervening
      atoms being dependent upon the type of P450 involved.

PMID- 15508430
TI  - Predicting pharmacokinetic herb-drug interactions.
AB  - In vitro and in vivo studies have indicated that the induction or inhibition of
      cytochrome P450 (CYP) is one of the major mechanisms for some clinically
      important pharmacokinetic herb-drug interactions. Thus, an attempt was made to
      predict pharmacokinetic herb-drug interactions using the pharmacokinetic
      principles that are used for predicting drug-drug interactions. The expected AUC
      ratio was mainly dependent on unbound herbal inhibitor concentration ([I]) and
      inhibition constant (Ki), hepatic fraction (fh), number of inhibitory herbal
      constituents (n) and metabolic pathway fraction in hepatic metabolism (fm). Herb
      drug interactions would be with low risk if sigma(i=1)n [[Ii]/Ki(i)] is less than
      0.1, medium risk if it is between 0.1 and 1.0, and high risk if it is greater
      than 1. For high clearance drugs, the change of fh x fm had minor influence on
      AUC ratio when sigma(i=1)n [[Ii]/Ki(i)] values were fixed. Similarly, fm did not
      affect the AUC ratio for low clearance drugs. It appeared likely to predict a
      herb-drug metabolic interaction when [I], Ki, fh, fm and n could be determined.
      However, many herb- and drug-related factors may cause difficulties with the
      prediction, and well-designed human studies are always necessary.

PMID- 15508431
TI  - Phenylalanine 4-monooxygenase and the S-oxidation of S-carboxymethyl-L-cysteine.
AB  - The identity of the enzyme responsible for the S-oxidation of the mucolytic S
      substituted L-cysteine drug, S-carboxymethyl-L-cysteine (SCMC), has been actively
      investigated for the last 10 years. A genetic polymorphism exists in the
      oxidation of the thioether moiety that has been identified as a disease
      susceptibility factor in a number of degenerative diseases. This polymorphism has
      also been implicated in the wide variation in clinical response to SCMC therapy
      in man. To date little is known about the molecular enzymology of this reaction
      but a previous investigation revealed that rat activated phenylalanine 4
      monooxygenase (PAH) could S-oxidise both Met- and S-methyl-L-cysteine (SMC) to
      their S-oxide metabolites. We have investigated the hypothesis that SCMC was also
      a substrate for activated PAH in the cytosolic faction of the Wistar rat. 1.
      Substrate and inhibitor investigation revealed that SCMC was a substrate for
      activated PAH activity in vitro. 2. The large aromatic amino acid hydroxylase
      monoclonal antibody and the Fe3+ chelator, deferoxamine, completely inhibited
      both Phe and SCMC oxidation to their respective metabolites. 3. Analysis of the
      Dixon plots revealed that both Phe and SCMC competitively inhibited each other's
      oxidation. 4. Correlation studies showed that the rate of production of Tyr was
      positively correlated to the production of both SCMC and SMC S-oxides in 20
      female Wistar rat hepatic cytosolic fractions. These results strongly support the
      hypothesis that PAH is the enzyme responsible for SCMC S-oxidation in the rat.

PMID- 15508432
TI  - Effect of isoflurane on proliferation and Na+,K+-ATPase activity of alveolar type
      II cells injured by hydrogen peroxide.
AB  - The influence of isoflurane (Iso) on proliferation and Na+,K+-ATPase activity of
      alveolar type II cells (ATII cells) injured by hydrogen peroxide (H2O2) was
      investigated. ATII cells isolated and purified from adult Sprague-Dawley rats
      were randomly divided into six groups: control group, 0.28 mM Iso group, 2.8 mM
      Iso group, 75 microM H2O2 group, 75 microM H2O2 + 0.28 mM Iso group, and 75
      microM H2O2 + 2.8 mM Iso group. After primary culture for 32 hours, the
      proliferation of ATII cells was detected by MTT assay, and after culture for 24
      hours the activity of Na+,K+-ATPase and lactate dehydrogenase (LDH) in the cells,
      and malonaldehyde (MDA) content of the culture medium, were measured by
      colorimetry. It was found that 0.28 mM and 2.8 mM Iso had no effect on the
      proliferation of ATII cells (p > 0.05), but 75 microM H2O2 inhibited their
      proliferation (p < 0.05) compared with untreated controls; 0.28 mM and 2.8 mM Iso
      significantly decreased Na+,K+-ATPase activity of ATII cells compared with
      untreated control cells (p < 0.05), and 75 microM H2O2 markedly decreased Na+,K+
      ATPase activity of ATII cells (p < 0.01) with untreated control cells. 0.28 mM
      and 2.8 mM Iso aggravated the decrease of Na+,K+-ATPase activity induced by H2O2.
      Iso had no effect on LDH activity and MDA content of the culture medium of normal
      ATII cells, but significantly increased LDH activity and MDA content of the
      culture medium of ATII cells injured by H2O2. These findings suggest that Iso
      itself may decrease the activity of Na+,K+-ATPase of ATII cells in vitro and
      further damage the cells' function under peroxidation conditions, but has no
      effect on the proliferation of ATII cells.

PMID- 15508433
TI  - Detection of ticarcillin-clavulonic acid susceptibility with microdilution method
      in Citrobacter, Hafnia, Proteus and some gram negative bacteria.
AB  - The broth dilution method has been regarded as a good alternative test for
      detection of susceptibilities to antimicrobial agents. In this study, the
      antimicrobial activity of ticarcillin-clavulonic acid (TIM) was investigated by
      the minimal inhibitory concentration (MIC) method on strains of Aeromonas,
      Citrobacter, Hafnia, Morganella, Proteus, Pseudomonas and gram negative bacteria
      isolated from raw milk. The isolate collection included 91 gram negative strains.
      Fifty-one (56.04%) isolates were found sensitive (MIC < or = 8 microg/ml), 12
      (13.19%) isolates were found intermediately sensitive (MIC 16-32 microg/ml), and
      28 (30.77%) isolates were found resistant (MIC > or = 64 microg/ml) to TIM.

PMID- 15508434
TI  - [The several problems and cautions in treatment of Helicobacter pylori
      infection].
AB  - Helicobacter pylori (H. pylori) infection is the main cause of most
      gastroduodenal diseases; this discovery has been a major breakthrough in
      gastroenterology, hematology, dermatology and pediatrics. Triple therapy,
      including two antibiotics, amoxicillin and clarithromycin, and a proton pump
      inhibitor given for a week has been recommended as the treatment of choice in
      guideline for diagnosis and treatment of H. pylori infection in Japanese Journal
      of Helicobacter Research. However, this treatment may fail for several reasons
      including bacterial resistance. Our aim to review the problems and cautions in
      diagnosis and treatment of H. pylori infection.

PMID- 15508436
TI  - [Indication and limitation of endoscopic surgical procedure for esophageal
      cancer].
AB  - Our standard procedure of thoracoscopic esophagectomy and indication of
      endoscopic surgery for thoracic esophageal cancer are described. The
      thoracoscopic esophagectomy is performed for cases without direct invasion to the
      adjacent structures, without massive lymph node involvement, and tolerable to
      left ipsi-lateral ventilation during surgery. Total operation time, time of
      thoracic procedure, and harvested lymph node of the past 243 thoracoscopic
      esohpagectomy cases are the same as the conventional open surgery. The blood loss
      of the thoracoscopic esophagectomy is less than that of the open. In the long
      term outcome, decreasing of the vital capacity is less in the thoracoscopic than
      open. Concerning to the postoperative complications, pneumonia and palsy of the
      recurrent laryngeal nerves occurred more frequently in the thoracoscopic surgery
      than open, but pneumonia has been getting less since introduction of the
      laparoscopic abdominal procedure. In conclusion, as manners of thoracoscopic
      esophagectomy and laparoscopic abdominal procedure differs in each hospital and
      have not yet approved, this surgery likely develops to a standard alternative
      once learning a high quality and sophisticated surgical maneuver under excellent
      magnified endoscopic view.

PMID- 15508435
TI  - [Laparoscopic surgery for gastric cancer].
AB  - Recently, the treatment of gastric cancer is becoming diversified. In Japan,
      gastrectomy with D2 lymphadenectomy has been recognized as a standard operation
      and has been performed widely for years. However, instead of D2 conventional
      gastric resection, various treatments using endoscopic or laparoscopic methods
      have been developed. Their usefulness and safety have been established, and the
      rate of detection of early gastric cancer has risen with the progress of medical
      technology and systems. The treatment suitable for the given stage must be
      chosen. In our department, we introduced laparoscopic operations and considered
      their usefulness and indication. Now, laparoscopic gastrectomy is recommended for
      cases in cStage I A and cStage I B of the guideline proposed by the Japanese
      Gastric Cancer Society. Future randomized controlled trials consisting of open
      surgery and laparoscopic gastrectomy are warranted.

PMID- 15508437
TI  - [Colorectal cancer].
AB  - Laparoscopic surgery for the cure of colorectal cancer has been a controversial
      issue. In this article summarizes the surgical procedures for right-and left
      sided colon cancer as well as the results of randomized controlled trials (RCTs)
      while comparing the long-term results of laparoscopic and open surgery. The RCTs
      revealed no significant differences in overall survival rate between laparoscopic
      and open procedures. In future, laparoscopic surgery will be a standard operation
      for a certain group of patients with colorectal cancer. Adequate skills of the
      surgical team and appropriate patient selection are essential.

PMID- 15508439
TI  - [Endoscopic surgery for gynecologic malignancy--less invasive, more radical].
AB  - The development of endoscopic equipment and surgical skills make more complicated
      procedures possible laparoscopically. The application of these techniques to
      oncologic surgery, which used to be basically the most invasive procedure, has
      become an important issue when considering patient well-being. For cervical and
      endometrial cancer we can perform a simple hysterectomy, type II or a type II
      radical hysterectomy as well as a pelvic and para-aortic lymphadenectomy. For
      ovarian cancer endoscopic procedures are advantageous for surgical staging, and
      even debulking surgery is possible in selected cases. The short-term outcome is
      excellent because post-operative recovery is quick, resulting in no delays in
      adjuvant therapy and a quick return to normal activity. As for the long-term
      results, although the number of cases and the observation period are limited, at
      present the outcome does not differ greatly from the results of conventional
      laparotomy.

PMID- 15508438
TI  - [Indication and role of the video-assisted thoracic surgery (VATS) for the
      primary lung cancer].
AB  - With advances in diagnostic technology, small peripheral lung cancer can be
      readily detected. Currently, the technique of endoscopic-surgery has become
      available for the treatment, and also video-assisted thoracic surgery (VATS) has
      proved useful for the treatment or diagnosis of early lung cancer. We report here
      our experience in surgical therapy with VATS and summarize recent reports which
      have focused on VATS for NSCLC. In the field of diagnosis, needle aspiration
      cytology or partial resection by VATS is available for small peripheral lesions.
      Either can play a significant role in staging for lung cancer or clarifying an
      unknown pleural effusion. VATS segmentectomy or partial resection with curability
      is applied to select cases. VATS lobectomy in NSCLC at clinical stage I could
      well be acceptable based on many recent reports and our result. This may be a
      valuable approach and a promising treatment for clinical stage II in the near
      future.

PMID- 15508440
TI  - [Indication and limitation of endoscopic surgery against urological cancer].
AB  - Endoscopic surgery in the urological field begins with cystoscopy and
      transurethral resection, and it develops into laparoscopic surgery. The
      indication of laparoscopic surgery for a malignant tumor also gradually expands.
      It is virtually impossible to search for urological cancer using laparoscopic
      procedures. In particular, out laparoscopic nephrectomy for renal cancer and
      transurethral resection for bladder cancer used widely in Japan. In the future,
      laparoscopic partial nephrectomy and the laparoscopic procedure for adrenal
      cancer and prostate cancer are considered to become widespread.

PMID- 15508441
TI  - [Breast cancer].
AB  - Endoscopic breast conserving surgery was developed originally in JAPAN. Minimally
      invasive technique improved cosmetic shape of breast conserving surgery by
      reducing the size of scar and changing the position of surgical wounds. In the
      present time, transaxillary endoscopic partial mastectomy by using special
      lifting systems, transaxillary total mastectomy by using Co 2 inflation,
      endoscopic partial mastectomy, by areola approach, and endoscopic axillary
      lymphnode dissection were performed as standerd procedure. The clinical results
      were showed that the efficacy of breast conserving operation were equal compared
      with normal procedure. As indication of breast conserving operation, patients
      with the tumor, that was within 3 cm, were selected, and the volume of resected
      specimen were also keep below 30% of total volume of breast as cosmetic
      indication for prevent metamorphosis of breast. In the case with metamorphosis
      after operation, some kind of reconstraction will be necessary. Minimally
      invasive breast surgery was improved cosmesis of breast surgery, and the patients
      with early breast cancer will take more benefits by using this technique.

PMID- 15508442
TI  - [Influence on 5-fluorouracil metabolism by combination of interferon-alpha and 5
      fluorouracil against human hepatocellular carcinoma xenografts].
AB  - To investigate the effect of biochemical modulation on antitumor activity shown
      by the combination of 5-Fluorouracil (5-FU) and interferon-alpha (IFN-alpha),
      experimental therapy was performed on human hepatocellular carcinoma cell (HuH7,
      PLC/PLF/5) xenografts inoculated into nude mice, using 5-FU and IFN-alpha, either
      alone or in combination. These agents showed antitumor activity in different
      degrees. Although IFN-alpha, given as 100,000 units/mouse/3 times/week
      subcutaneously x 6, and 5-FU, given as 0.5 mg/mouse/3 times/week
      intraperitoneally, showed addititive antitumor effect against HuH7 and PLC/PLF/5,
      the activities of thymidylate synthase (TS), dihydropyrimidine dehydrogenase
      (DPD), thymidine phosphorylase (TP), orotate phosphoribosyltransferase (OPRT),
      uridine phosphorylase (UP) and uridine kinase (UK) were not significantly
      influenced in the tumors treated with the 5-FU/IFN-alpha combination, compared
      with those treated with 5-FU or IFN-alpha alone. This suggested that antitumor
      activity of 5-FU and IFN-alpha in combination was not significantly involved in 5
      FU metabolism in two human hepatocellular carcinoma cell lines examined.

PMID- 15508443
TI  - [Postoperative changes in serum lipid levels of breast cancer and adjuvant
      chemotherapy].
AB  - Postoperative adjuvant drugs are usually given long-term for breast cancer to
      obtain various effects and their effects on serum lipid level changes were
      studied. Between June 1990 and May 2003, changes in serum levels of five serum
      lipids, cholesterol (CHO), triglyceride (TG), phospholipid (PL), free fatty acid
      (FFA), and high-density lipoprotein-cholesterol (HDL-C), were quantitated for 453
      surgically-treated patients with breast cancer. Postoperative adjuvant settings
      were: 1. no drug; 2. Goserelin (G) of subcutaneous gradual release form; 3.
      tamoxifen; 4. oral fluoropyrimidines, i. e. tegafur, carmofur and doxyfluridine;
      and 5. oral alkylating agents, i. e. carboquone or cyclophosphamide. Preoperative
      levels of all five lipids correlated with age until 70, and postoperative levels
      of all five increased. The CHO level increased in patients treated with G,
      fluoropyrimidines and oral alkylating agents, decreased in patients treated with
      tamoxifen, and was stable in patients without adjuvant treatment. While the
      increase in the CHO level in G or decrease in tamoxifen was restored nearly to
      the preoperative level, the changes in patients with fluoropyrimidines or
      alkylating agents continued after five-year administration. Multiple regression
      analysis revealed significant effects of preoperative levels of all lipids,
      including T for CHO, G and oral fluoropyrimidines for TG, G for FFA, and oral
      fluoropyrimidines for PL. While postoperative adjuvant treatment for breast
      cancer affects changes in serum lipid levels as a function of preoperative level
      and age, it seems to be due to direct or indirect endocrine milieu.

PMID- 15508445
TI  - [Combination therapy with Anastrozole and 5'-DFUR as a treatment for metastatic
      breast cancer].
AB  - For metastatic breast cancer patients who have hormone receptor-positive tumors,
      hormonal therapy aiming at optimal palliation and prolongation of life is the
      initial treatment of choice. To enhance the effect of hormonal monotherapy, a
      combination therapy with Anastrozole 1 mg po and 5'-DFUR 800 mg po daily was
      given to 11 patients with metastatic breast cancer. At a median follow-up period
      of 15 months, the overall response rate was 45.5%. The median duration of
      response in responders was 25 months. The overall median survival for the entire
      series was 15 months after the start of treatment. No patients complained of
      adverse events of grade 2 and over. This combination therapy with good response
      and little side effects is useful for metastatic breast cancer patients.

PMID- 15508444
TI  - [Therapeutic effects of Anastrozole in patients with advanced and recurrent
      breast cancer].
AB  - We reviewed therapeutic effects and harmful side effects in 33 patients with
      advanced or recurrent breast cancer who underwent treatment with Anastrozole 1
      mg/day in our department. The patients ranged in age from 40 to 83 years old
      (median, 59). The Performance Status was 0-2, and there was 1 case of advanced
      breast cancer and 32 cases of recurrent breast cancer. The duration of disease
      was from 5 to 233 months (median, 50 months). The estrogen and/or progesterone
      receptor-positive rate was 72.7%. Metastatic sites were in multiple organs in 9
      cases, in the lung only in 1 case, in bone only in 12 cases, and in soft tissue
      only in 10 cases. First-line therapy was used in 10 cases, second-line therapy in
      6 cases, and above third-line therapy in 17 cases. There was a complete response
      in 3 cases, partial response in 5 cases, no long change in 13 cases, no change in
      9 cases, and progressive disease in 3 cases. The response rate was 24.3%, The
      response period ranged from 2 to 22 months (median, 8 months), and clinical
      benefit was achieved in 63.7%. The clinical benefit rates for first-line were
      60%, second-line 83.3% and above third-line therapy 58.8%. The response rate for
      patients with breast cancer resistant to Anthracyclines and/or Taxanes was 20%.
      Time-to-progression ranged from 2 to 28 months (median, 11 months), and overall
      survival ranged from 7 to 30 months (median, 15 months). The most frequent
      harmful side effects were rise in total cholesterol, general fatigue, hot flashes
      and arthralgia (9.1%). In this study, we confirmed the availability and safety of
      Anastrozole, which was suggested to be a useful drug in salvage therapy for
      patients having resistance to Anthracyclines and/or Taxanes, not only but also
      useful as a first- or second-line therapy.

PMID- 15508446
TI  - [The efficacy of Shakuyaku-Kanzo-to for peripheral nerve dysfunction in
      paclitaxel combination chemotherapy for epithelial ovarian carcinoma].
AB  - Shakuyaku-Kanzo-to was first medicated for muscular pain which was called
      Komuragaeri, and it has been reported that it is effective for peripheral nerve
      dysfunction such as arthralgia and numbness. Recently, Paclitaxel (T) and
      Carboplatin (J) combination chemotherapy (TJ chemotherapy) has been a standard
      first-line chemotherapy for epithelial ovarian carcinoma. For the arthralgia and
      muscular pain occurring in TJ chemotherapy, non-steroid-anti-inflammatory drugs
      (NSAIDs), Vitamin B12 (VB12) and Shakuyaku-Kanzo-to are the major medications. In
      this study, we examined twenty-one cases in which arthralgia and muscular pain
      occurred in TJ chemotherapy (including 16 cases as first-line chemotherapy). In
      all cases, patients took 7.5 g of Shakuyaku-Kanzo-to orally per day for eight
      days. We investigated the efficacy of Shakuyaku-Kanzo-to retrospectively with the
      following results. In nine cases (43%), Shakuyaku-Kanzo-to was effective in
      reducing pain. Especially in TJ chemotherapy as first-line chemotherapy,
      Shakuyaku-Kanzo-to was even more effective in reducing pain. We suggested that
      Paclitaxel combination chemotherapy with Shakuyaku-Kanzo-to taken orally is a
      more safe and tolerable way to reduce pain in epithelial ovarian carcinoma.

PMID- 15508447
TI  - [Two cases of recurrent lung cancer successfully treated with concurrent
      radiochemotherapy with vinorelbine plus cisplatin].
AB  - Case 1:A 62-year-old man, who had undergone right upper lobectomy for lung
      squamous cell carcinoma (pT2pN2M0, stage IIA) 4 months earlier, was diagnosed as
      mediastinal lymph node recurrence by chest CT. Case 2: A 63-year-old woman, who
      had undergone right middle-lower lobectomy for lung squamous cell carcinoma
      (pT2pN1M0, stage IIB) 16 months earlier, was diagnosed as hilar lymph node
      recurrence by chest CT. Both patients underwent radiochemotherapy with 2 cycles
      of cisplatin (CDDP) 80 mg/m2 on day 1 and vinorelbine (VNR) 15 mg/m2 on day 1 and
      another day (day 8-16), and concurrent radiation (60 Gy/30 fr) for mediastinum.
      After this treatment, a partial response (PR) in case 1 and a complete response
      (CR) in case 2 were achieved, and neither patient showed any relapse after 3
      years of the treatment. Adverse reactions were grade 3 neutropenia in both
      patients and transient hemiparalysis in case 2. Concurrent radiochemotherapy with
      cisplatin and vinorelbine is considered effective without serious side effects
      for postoperative recurrence in localized mediastinal lymph nodes of non-small
      cell lung cancer.

PMID- 15508448
TI  - [Histoculture drug response assay for solitary fibrous tumor--a case report].
AB  - A 49-year-old male was referred to our hospital because of an abnormal shadow in
      his left lower lung field on chest X-ray. Magnetic resonance imaging scans
      revealed a large mass on the left diaphragm. The tumor was surgically extirpated.
      The tumor, encapsulated and growing from the center of the left diaphragm,
      measured 18 x 8 x 4 cm and weighed 440 g. Microscopic examination revealed a
      solitary fibrous tumor with mitotic activity of 7/ 50 hpf. Immunohistochemically,
      the tumor was negative for cytokeratin, s-100 protein, desmin, and alpha-smooth
      muscle actin, while positive for vimentin and CD34. On a histoculture drug
      response assay using the resected tissue, the tumor was sensitive to 5-FU,
      adriamycin, mitomycin C and docetaxel, and resistant to cisplatin, irinotecan,
      and gemcitabine.

PMID- 15508449
TI  - [A case of aged advanced breast cancer with multiple lung and pleural metastases
      responding to exemestane monotherapy].
AB  - A 76-year-old woman was diagnosed with advanced breast cancer with bilateral
      multiple lung and pleural metastases in March 2003. Her CEA and CA15-3 level were
      7.6 ng/ml and 98.3 U/l, respectively. However, she refused intensive chemotherapy
      and chose a hormonal monotherapy with exemestane instead. The patient then did
      not return to our department for about one year, during which time she continued
      to take the same medications. When she visited again, CEA and CA15-3 level were
      reduced to within the normal range, and her multiple lung and pleural metastases
      were found to have almost completely disappeared upon computed tomography.
      Exemestane is expected to be an effective agent for the treatment of hormonal
      receptor-positive postmenopausal woman with life-threatening advanced breast
      cancer.

PMID- 15508450
TI  - [A case of successful management of nonresectable pancreas cancer with liver
      metastasis by intra-arterial infusion chemotherapy with gemcitabine
      hydrochloride, 5-FU, CDDP and administration of tegafur/uracil].
AB  - We report a case of a 43-year-old man with liver metastasis of advanced
      pancreatic cancer successfully treated with intra-arterial regional chemotherapy.
      The patient was admitted to our hospital suffering from anorexia and back pain.
      Abdominal CT showed pancreatic tail cancer with liver and Schnitzler metastasis.
      We decided a curative operation was impossible. Then, enteric-coated
      tegafur/uracil (400 mg) was administered. Simultaneously, intraarterial infusion
      with CDDP, 5-fluorouracil (500 mg) and infusion of gemcitabine (1,000 mg) with 50
      microg of AT-II was given once a week. After 3 courses, the pancreatic tumor was
      reduced and the tumor markers decreased. Multiple metastatic liver tumors
      remarkably decreased. As a result, the maximum diameter of the pancreatic tumor
      decreased from 7 cm to 5 cm on the CT-scan. Serum carbohydrate antigen 19-9 (CA19
      9) decreased from 122,000 U/ml to 10,200 U/ml. Moreover, the performance status
      of patient also improved. He was able to receive outpatient treatment despite his
      terminal cancer. Furthermore, the patient can take sufficient meals without any
      adverse effects. His quality of life has been preserved. This regimen could well
      be effective for advanced pancreatic cancer.

PMID- 15508451
TI  - [A case of recurrent gallbladder cancer responding to combination chemotherapy of
      TS-1 and CDDP].
AB  - A 76-year-old man suffering from advanced gallbladder cancer after hepato
      pancreaticoduodenectomy had cholangitis and serum elevation of CA19-9 2 years and
      6 months after the operation. A recurrent tumor had been recognized from the
      hilar to the surrounding inferior vena cava, and stenosis of jejunum utilized for
      pancreaticocholedoco-jejunostomy. A bypass operation of jejunum was performed.
      Combination chemotherapy with TS-1 100 mg/day (3 weeks) and CDDP 30 mg/day (day
      1, 8 drip infusion) in 1 course was performed, and a partial response (PR) was
      noted. Diarrhea of grade III and decreased WBC of grade II were recognized, and
      were improved. Two courses of the same chemotherapeutic regimen were carried out.
      Among 5 months, recurrent tumor showed preservation of PR. Into 3 course of
      chemotherapy, radiation therapy was selected for second opinion. But recurrent
      tumor was enlarged acutely, and radiation therapy was stopped. He died 15 months
      after the first detection of chemotherapy. The combination chemotherapy of TS-1
      and CDDP seems to be beneficial therapy for advanced gallbladder cancer.

PMID- 15508452
TI  - [A complete response using TS-1 in a patient with paramesenteric lymph node
      recurrence of gastric cancer].
AB  - A 86-year-old male patient underwent distal gastrectomy, D2 lymph node dissection
      for type 2 gastric cancer. Five months after the surgery, abdominal computed
      tomography (CT) revealed paramesenteric vein lymph node recurrence (# 14v), 12 mm
      in size. TS-1 (80 mg/day) was administered for 28 days, followed by 14 days rest,
      as one course. A complete response was obtained after the second course. The
      patient has been in good health without a recurrence for 36 weeks after 5
      courses. As for adverse events, leukopenia (grade 2) was observed temporarily but
      required no treatment.

PMID- 15508453
TI  - [Two cases of postoperative recurrence of gastric GIST treated by imatinib].
AB  - We report two cases of postoperative recurrence of gastrointestinal stromal tumor
      (GIST) treated by the tyrosine kinase inhibitor imatinib mesylate (IM), and
      discuss some important items. Case 1: This 63-year-old Japanese man received a
      partial gastrectomy for leiomyosarcoma in 1993. Partial hepatectomy and proximal
      gastrectomy were performed for liver metastasis and local recurrence in 2001.
      However, 5 months after surgery, a CT scan showed multiple tumors in the liver,
      lung and thyroid. The patient was treated with 300 mg of IM once daily with
      transient grade 2 neutropenia and intestinal bleeding. Though the response to
      treatment was SD-PR initially, a CT scan 15 months after initial treatment
      demonstrated the regrowth of the tumor in his liver. Case 2: A 63-year-old
      Japanese woman was treated with 200 mg of IM once daily for multiple liver
      metastases after gastrectomy for GIST with grade 3 neutropenia and edema of legs.
      The response to treatment was SD, and continued for 12 months. IM is the
      treatment of choice for unresectable recurrence of GIST. However, some problems
      remained. Both basic and clinical research is necessary to increase the
      therapeutic efficacy of IM.

PMID- 15508454
TI  - [A case of recurrent gastric cancer tolerant to TS-1 therapy successfully treated
      by TS-1 combined with docetaxel].
AB  - We report a case of a 58-year-old man with advanced gastric cancer producing
      sialyl-Tn antigen (STN). Total gastrectomy with distal pancreatectomy and
      splenectomy was performed. Pathological staging was IV (T 3 N 2 CY1), and most of
      the cancer cells were strongly positive for anti-STN antibody on
      immunohistochemical stainings. Serum STN level before the operation was 2,500
      U/ml, and the value significantly decreased to the normal range (< 45 U/ml) 2
      months after the operation. Low-dose FP (5-FU+CDDP) followed by TS-1 alone (80
      mg/day) had been performed as adjuvant chemotherapy. Jaundice appeared and the
      serum STN level increased again 22 months after the operation. He was diagnosed
      with a recurrence in the hilar lymph node of the liver. After implantation of
      expandable stent in the common bile duct, triweekly docetaxel therapy with TS-1
      administration (day 1-14) has been performed. Three courses of this therapy have
      induced a complete response of the recurrent lymph node and the normalization of
      the serum STN value. No major adverse reaction to this therapy was observed. A
      complete response and good patient QOL have been achieved during follow-up 8
      months after the administration of TS-1 with docetaxel. This case suggests that
      patients with recurrent gastric cancer who have undergone prior therapy with TS-1
      alone could benefit from TS-1 with docetaxel therapy as a second line.

PMID- 15508455
TI  - [A case of gastric cancer with abdominal paraaortic lymph node metastases
      responding to TS-1 plus CDDP neoadjuvant chemotherapy].
AB  - A 62-year-old woman was admitted because of epigastralgia and tarry stool. An
      endoscopic examination revealed type 3 cancer in the lower body of the stomach,
      and abdominal CT scan demonstrated enlarged abdominal paraaortic lymph nodes. The
      preoperative diagnosis was cStage IV gastric cancer (cT3, cN3, cH0, cP0, cM0).
      Since a curative operation was deemed impossible, we started neoadjuvant
      chemotherapy using TS1 plus cisplatin (CDDP) for downstaging. TS-1 (100 mg/day)
      was orally administered for 3 weeks, and CDDP (90 mg/body) was administered
      intravenously on day 8. Appetite loss of grade 3 and leucopenia of grade 1 were
      observed. After two courses of chemotherapy, the primary lesion was reduced in
      size, and the paraaortic lymph nodes disappeared on abdominal CT scan. The serum
      tumor marker became normal. Subsequently, she underwent curative total
      gastrectomy with splenectomy and lymph node dissection. Histological examination
      of the primary lesion revealed marked fibrosis and a small amount of residual
      cancer cells. The histological changes by neoadjuvant chemotherapy were judged to
      be grade 2 for the main tumor. It is suggested that neoadjuvant chemotherapy
      using TS-1 plus CDDP is effective for advanced gastric cancer with massive lymph
      node metastases.

PMID- 15508456
TI  - [A case of multiple pulmonary metastases from rectal cancer effectively treated
      by TS-1 and low-dose CDDP therapy].
AB  - We report a patient with multiple pulmonary metastases from rectal cancer
      effectively treated with TS-1 and low-dose CDDP combination chemotherapy. The
      patient was a 61-year-old man with rectal cancer and multiple pulmonary
      metastases. He had undergone abdominoperineal excision of the rectum at another
      hospital before this hospitalization. After the operation, we treated the patient
      by the combination chemotherapy of TS-1 and low-dose CDDP during his hospital
      stay and in the outpatient clinic after hospital discharge. After the
      chemotherapy was started, tumor markers decreased, and finally were in the normal
      range. The pulmonary metastatic lesions were remarkably reduced on CT, and the
      effect of this therapy was PR. No severe side effect was observed throughout the
      treatment. This combination chemotherapy is considered to be an effective therapy
      for colorectal cancer with good QOL.

PMID- 15508457
TI  - [A case of rectal cancer with multiple liver and peritoneal metastases that
      responded dramatically to low-dose 5-FU plus LV and CDDP combination
      chemotherapy].
AB  - We have experienced successful treatment of a multiple hepatic metastasis of
      rectal cancer with combination chemotherapy. The patient is a 57-year-old male
      with bowel obstruction accompanied by rectal cancer (SE, N3, P1, H3, M (-) stage
      IV) who underwent a Hartmann operation with D3 lymph node dissection on July 6,
      2000. The histopathological findings revealed a well-differentiated
      adenocarcinoma (se, INFbeta, n3, ly2, v2, p1). From the 11th postoperative day,
      combination chemotherapy using 5-FU 750 mg/day and LV 300 mg/day was performed
      once a week. When he underwent 5 combination chemotherapy treatments, adverse
      effects of grade 3 occurred, and the serum CEA level rose rapidly. We changed his
      regimen at that time. He underwent 2 courses of combination chemotherapy with 5
      FU 500 mg/day and CDDP 10 mg/day for 5 days. Additional courses of combination
      chemotherapy with 5-FU 500 mg/day, LV 25 mg/day and CDDP 10 mg/day were performed
      weekly in the outpatient department. The treatment was effective, and a complete
      response (CR) was noted 4 months after the chemotherapy. The same combination
      chemotherapy was performed biweekly for one year after CR. The patient has been
      receiving a subsequent single administration of UFT and has remained in remission
      for 3 years and 7 months after surgery.

PMID- 15508458
TI  - [Advances in sentinel node biopsy for breast cancer].
AB  - SN biopsy (SNB) has evolved rapidly during the past decade and has now become a
      standard of surgical care for patients with breast cancer. The primary purpose of
      SNB is to minimize patient morbidity from axillary staging, but SNB also presents
      research opportunities to further understand the role of the sentinel node in the
      natural history of breast cancer. We have attempted to highlight several issues
      regarding SN and its biopsy in this review, including:(1) Investigation of the
      optimal particle size for radiotracers. The success of SNB is, in large part,
      attributed to the particle size of radiolabeled tracers. Electron microscopy
      demonstrated significant accumulation of the tracer (tin colloid) in harvested
      SN, of which particle sizes were in the range of 100-150 nm. Therefore, this
      appeared to be a suitable particle size for SN identification. (2) Invention of a
      new gamma probe. A cord-and boxless handheld gamma probe was invented, which was
      more sensitive to radioactivity and involved a background subtraction function
      based on defined criteria. (3) Characterization of the immunologic response
      against tumor antigens. Fluorescence-activated cell sorting (FACS) analyses were
      performed to determine the phenotypic characteristics of B cells and T cells in
      SN. They revealed an increase in B cells expressing co-stimulated molecules as
      antigen-presenting cells in SN, compared with non-SN. With respect to T cells, a
      heterogeneous pattern of naive and memory T cells (TCM) was demonstrated in SN,
      in contrast to homogeneous pattern with TCM in non-SN. These results may support
      the concept that B cells play a significant role in antigen presentation required
      for T cell activation. Studies are currently in progress to test these
      possibilities.

PMID- 15508459
TI  - [Lung cancer].
AB  - Tumor markers are defined as substances which are produced by cancer cells or non
      cancer cells reactive to cancer cells, and reflect the cancer status, such as its
      presence, characteristics, and volume. Clinically, many tumor markers are useful
      not only to assess the presence/absence of cancer, the primary site, histology,
      stage, and recurrence, but also to monitor the anti-cancer therapy. Tumor markers
      for lung cancer play only supporting roles because of their limited sensitivity
      and specificity, but they are clinically essential to daily medical oncology.
      This review addresses 6 important tumor markers for lung cancer, namely, CEA,
      SLX, CYFRA, SCC, ProGRP, and NSE.

PMID- 15508460
TI  - Overview of the Social Transition in the North project 1995- 1998.
AB  - OBJECTIVE: This paper describes the overall aims and design of the Social
      Transitions in the North study. The objective of the STN study was to assess how
      epidemiological, demographic and domestic changes have affected Northern
      communities. STUDY DESIGN: Sixteen communities in the Russian Far East and Alaska
      were compared. Survey data were collected in three phases with a response rate of
      70%. METHODS: The experiences of indigenous peoples with demographic,
      epidemiological and domestic changes were measured using forced-choice
      questionnaires, focus groups, oral histories, protocol interviews, interviews
      with institutional informants, genealogies and analysis of secondary data.
      RESULTS: The principal researchers died during a boating accident before the
      analysis phase. Alaska researchers were asked to review the data for utility.
      CONCLUSIONS: The STN data was developed using rigorous cross-cultural research
      team. It was be used by social science researchers and others to better
      understand the impact of rapid changes in the Arctic.

PMID- 15508461
TI  - Arctic research at three levels.
AB  - This paper is a posthumous publication of a Steven McNabb's presentation to the
      1993 annual meeting of the American Anthropological Association. In it he
      described how the Social Transitions in the North research project involved
      explicit cross-cultural contact or participation at three levels: between
      scientists and public agencies; between scientists and study populations; and
      between research teams themselves. He explored a few of the entanglements and
      opportunities that arise in those interactions. Dr. McNabb urged northern
      researchers to avoid embracing rigid standards, for they will result in more
      entanglements and fewer opportunities. On the otherhand, if researchers are open
      minded, they will be able to treat each dilemma as an opportunity that will make
      for better science.

PMID- 15508462
TI  - From respect to rights to entitlement, blocked aspirations and suicidal behavior.
AB  - Dr. Bill Richards was a noted psychiatrist who worked with Alaska Native people
      for many years. This paper was taken from notes he used for a slide presentation
      at a conference. In it, he discussed the possible relationship between rapid
      social change and the increasing rates of suicide among northern people. He
      summarized the limitations in the existing suicide data, including its
      essentially descriptive nature, the short time periods of study, small numbers of
      observations and lack of complete health service use information which could help
      anticipate a suicidal event. Richards noted the importance of suicide as an
      indicator condition that could be used to link social survey and health
      information data bases. He closed his paper with a discussion of the transition
      from an era of "rights" to one of "entitlements," and described his observations
      of growing overt anger and hostile dependency upon government programs. Last,
      Richards related his concerns over the collection of health service use and
      epidemiological data associated with a suicidal event.

PMID- 15508463
TI  - The preliminary assessment of the Social Transition in the North dataset: a
      comparison of STN survey and enumeration data for selected Northwest Alaskan
      communities.
AB  - OBJECTIVE: This study compared the results from STN survey data with a mailback
      health study of the same communities to assess the reliability of the STN data.
      STUDY DESIGN. Sample characteristics and respondes to health questions were
      compared through secondary data analysis. Data from the STN sample was compared
      to an enumeration study for the same or similar questions, including demographic
      characteristics and health status indicators, were compared. METHODS: The STN
      study used the sample of 715 households in 18 Alaskan and Russian Far East
      communities to obtain data on the demographic transition, epidemiological
      transition and domestic transition of residents in northern communities. A study
      of the health and human service needs was conducted in Northwest Alaska using a
      mailback health questionnaire within a few years of the STN study. RESULTS: Both
      data sets appear to be taken from similar populations. Responses to health
      questions show marked similarities. CONCLUSION: The comparison strongly suggests
      that the STN data is representative of northern Alaska communities surveyed and
      can be a valuable source of reliable data on the health and welfare of northern
      communities. The data on the self-reported prevalence of health conditions may
      not be useful at the community level.

PMID- 15508464
TI  - The health of elders: a comparison of communities across the Bering Strait.
AB  - OBJECTIVE: Compare the self-reported health status of a cohort of 58+ individuals
      in sixteen communities on either side of the Bering Strait. STUDY DESIGN: Multi
      method including formal surveys and ethnographic research. METHODS: Approximately
      1,146 survey questionnaires were completed. A sample of 747 of these interviews
      were used for this analysis, of which 88 were 58+ years of age and 659 were
      adults 18-57. RESULT: On all self reported measures of general health, chronic
      illness and depression, Russian elders reported higher rates of poor health than
      did their American congeners. However, the segment of the sample in most distress
      was Russian adults 18-57. Not one of these 361 individuals reported their health
      as "very good", while nearly a third reported poor health and chronic illness. In
      addition, about 2/3rds (compared to half the Russian elderly) reported a
      constellation of symptoms related to depression. Psychologically (using these
      measures) the most resilient cohort were Alaskan elders. One result of this
      research that is of tremendous concern is the fact that over two thirds of the
      STN males, both Alaskan and Russian, under the age of 58 smoke. This is an
      extraordinary proportion and is easily double the rate for individuals of similar
      age within the U.S. CONCLUSIONS: For Alaskan elderly, no other segment in the
      U.S. faces the level of difficulty in access to health services even though these
      services are incomparable by Russian standards. In addition, the extremely high
      levels of behavioral risk from smoking and other factors indicate substantial
      difficulties and increasing demand for health services in the near future. In
      comparison Russian elderly populations face almost uni-maginable difficulties.

PMID- 15508465
TI  - Family support for first-time mothers in the Aleutians.
AB  - OBJECTIVE: This paper examines changes in the support first-time mothers receive
      from parents and other relatives in Aleutian communities. STUDY DESIGN: Data were
      collected as part of the Social Transitions in the North study. Data used in this
      study came from the Aleutian communities of St. Paul, Akutan, Unalaska and Sand
      Point, Alaska. METHODS: The STN study data using a combination of background
      ethnographies, a detailed survey instrument, open-ended interviews, Kleinman
      focus groups and genealogies. These were meant to complement and build upon each
      other. RESULT: While it appears that teenage pregnancies still occur while the
      unmarried mother lives with her parents, the social context of such situations
      has changed considerably since the 1970s. Many respondents indicated that
      although families are more fragmented than previously, the responsibility for
      raising children continues to be shared throughout the extended family. Nuclear
      family households have become more prevalent. Government transfers and housing
      have become more readily available for young single mothers. CONCLUSIONS: The
      extended family is still a viable social and economic unit in Aleutian villages.
      People may live in nuclear family households, but parents, grandparents and other
      relatives are still a strong support for young mothers.

PMID- 15508466
TI  - Potential future studies on the nutritional status among indigenous peoples in
      Alaska and the Russian Far East: preliminary assessment of the Social Transition
      in the North data set.
AB  - OBJECTIVE: The purpose of this assessment is to examine the nutrition-related
      health data collected during the Social Transitions of the North (STN) study for
      understanding cultural differences between nations and the impact on nutritional
      status. METHODS: The nutrition data in the STN study was collected in two regions
      of Alaska (Northwest Arctic and the Aleutian Islands) and in two regions of the
      Russian Far East (Kamchatka and Chukotka). The health questionnaire explored
      several factors that may contribute to identifying the nutritional status of the
      study populations. These factors were appetite, weight, subsistence food
      consumption, vitamin or mineral supplements use self-perception of health,
      special diets, and number of meals consumed with relatives. RESULTS: US
      populations were heavier than the Russian population (p = 0.0001). Both the
      Alaskan and Russian populations are frequent users of subsistence foods. The US
      respondents reported consuming 75% or more of the total protein as subsistence
      protein more often (40%) than the Russian respondents (25%). CONCLUSION: US
      respondents perceive themselves as healthier than their Russian counterparts. The
      US respondents consumed greater amounts of subsistence foods in general, and more
      of their diet over the year is made up of Native protein.

PMID- 15508467
TI  - Domestic function and Inupiaq households.
AB  - OBJECTIVE: This paper examines domestic transitions among Inupiaq households,
      including changes in household composition, household functions, kin networks,
      and possibly in cultural ideologies such as ethics of cooperation, achievement,
      and economic attainment. STUDY DESIGN: STN survey data included extensive
      information on the characteristics of households. This survey data is combined
      with STN project data from ethnographic accounts and focus groups; socio-economic
      trend data; and demographic and epidemiological information about community
      change to gain a clear picture of Inupiaq family structure. RESULTS: Household
      data reveal that Inupiaq households living under one roof are rarely an
      independent entity, either economically or in other ways. Members of one
      household seldom carry out all the social and economic functions needed to
      sustain the household. Instead, relatives or friends from two or more households
      frequently form social networks that support several households. CONCLUSION:
      Inupiaq families were found to be opportunistic, flexible, and creative in
      responding to the challenges of daily life. Domestic functions are divided among
      a network of kinspeople--people who may live in several separate households and
      even in separate communities--but who consider themselves related.

PMID- 15508468
TI  - The Social Transition in the North: collection and data access protocols.
AB  - OBJECTIVE: These protocols were designed to provide access to the Social
      Transition in the North (STN) collection and data set. METHOD: Staff at the (UAA)
      Institute for Circumpolar Health Studies (ICHS) reviewed, organized, inventoried,
      and cataloged the STN collection. RESULTS: Most of the materials in the
      collection are available from the UAA Archives and Manuscripts Department,
      Consortium Library. Documents and data containing sensitive information are
      maintained by ICHS to assure confidentiality of research participants.
      CONCLUSION: These access protocols allow researchers to obtain access to this
      valuable data set consistent with US research policy while protecting the
      integrity of the data and the confidentiality of the participants.

PMID- 15508469
TI  - Visual deficits and dyslexia.

PMID- 15508470
TI  - Federal law and the accommodation of students with LD: the lawyers' look at the
      BU decision.
AB  - This article explores the genesis and development of the Guckenberger v. Boston
      University case, detailing the pertinent facts and issues of the case and
      analyzing the court's decision. The overall question posed by the case (as
      considered from the perspective of the plaintiffs' attorneys) was whether Boston
      University violated federal law in its response to the requests for reasonable
      accommodations by students with learning disabilities. The article quotes
      primarily from the decision issued by Federal Judge Patti Saris. The court's
      decision signified an important development in the field of higher education and
      set an extraordinary precedent in favor of students with disabilities under both
      the Americans with Disabilities Act and the Rehabilitation Act of 1973.

PMID- 15508471
TI  - Between passion and policy: litigating the Guckenberger case.
AB  - This article describes the Guckenberger lawsuit from the perspective of the
      attorneys who litigated the case on behalf of Boston University. It first
      discusses the events leading to the lawsuit, including then-Provost Jon
      Westling's speeches, his articulation of new policies regarding documentation for
      accommodations requests, and the university's refusal to allow course
      substitutions for required foreign language courses. The article then describes
      the main events in the lawsuit that resulted from those policy changes, focusing
      first on pretrial matters, such as the university's search for experts, the
      various motions filed prior to trial, and tactical issues. Moving to the trial
      itself, the article discusses the nature of the witness and expert testimony
      presented to the court and touches on the differences of opinion expressed at
      trial by experts in the field of learning disabilities. Finally, the article sets
      forth the court's ruling on the major issues in the case and reflects on the
      case's impact on institutions of higher education.

PMID- 15508472
TI  - Issues in the definition and diagnosis of learning disabilities: a perspective on
      Guckenberger v. Boston University.
AB  - This article reviews issues related to the definition of learning disabilities in
      the context of the Guckenberger v. Boston University case. Four major questions
      are addressed: (a) Who is learning disabled? (b) How should learning disabilities
      be assessed? (c) Who is qualified to make a decision about whether or not an
      individual has a learning disability? and (d) What accommodations should be
      provided by a postsecondary institution and how should they be selected? Although
      these are complicated and difficult questions, it is possible to develop a
      simple, reasonable classification system for learning disabilities, and to
      conduct assessments based on a coherent and relevant set of achievement tests in
      which individuals who score below a cutoff are considered learning disabled.
      Scores on IQ tests are irrelevant and not useful and may even be discriminatory.
      The issues of decision making regarding learning disabilities and appropriate
      accommodations remain significant dilemmas for the field; resolution of these
      issues seems virtually impossible without agreement on appropriate procedures for
      the definition, identification, and assessment of learning disabilities.

PMID- 15508473
TI  - The case for course substitutions as a reasonable accommodation for students with
      foreign language learning difficulties.
AB  - It has been observed for decades that some students have a particularly difficult
      time learning another language. Colleges and universities have an obligation to
      offer special language programs designed to help these students succeed in their
      attempts to learn another language. However, for those few students who cannot
      learn another language even with special instruction, allowing them to meet the
      foreign language requirement though the substitution of related courses is
      appropriate and does not constitute a fundamental alteration of the goals of a
      liberal education.

PMID- 15508474
TI  - Students classified as LD and the college foreign language requirement:
      replication and comparison studies.
AB  - Two studies examined students classified as having learning disabilities (LD) who
      had received course substitutions for the college foreign language (FL)
      requirement. In the first study, 42 students at one university were divided into
      groups and compared on measures of IQ, academic achievement, FL aptitude, college
      grade point average (GPA), and FL and English grades. Findings showed that most
      of the 42 students had been classified as LD in college after experiencing
      problems in FL courses. Comparisons based on students' performance on measures of
      FL aptitude, native language skill, and performance in FL courses showed few
      significant group differences. In the second study, the 42 students from the
      first study were compared with 86 students at another university who had also
      been classified as LD and received course substitutions for the college FL
      requirement. Comparisons on demographic information and measures of IQ, academic
      achievement, FL aptitude, college GPA, and FL GPA showed few significant
      differences between the two groups. Both studies suggest that students classified
      as LD at different universities exhibit similar demographic, cognitive, academic
      achievement, and FL aptitude profiles and that educators should not make the a
      priori assumption that students classified as LD require course substitutions for
      the FL requirement or experience problems with FL learning.

PMID- 15508475
TI  - The sociopsychometrics of learning disabilities.
AB  - The Boston University (BU) case illustrates how the psychometrics of ability
      differences interact with the concept of learning disability and with the
      sociopolitics of schooling and society. It also illustrates that learning
      disabilities advocacy will not be on a sound footing as long as the field refuses
      to rid itself of its IQ fetishism, refuses to jettison its fixation on aptitude
      achievement discrepancy, and fails to free clinical practice from the
      pseudoscientific neurology that plagued the field in the 1970s. A more inclusive
      definition of learning disability--one that abandons discrepancy notions--and a
      more self-critical attitude toward its own claims would advance the field of
      learning disabilities and help to rid it of distractions such as the BU case.

PMID- 15508476
TI  - An update on NCAA college freshman academic requirements: the impact on students
      with LD.
AB  - A recent landmark settlement between the National Collegiate Athletic Association
      (NCAA) and the U.S. Department of Justice addressed many crucial issues relating
      to the eligibility of high school students with learning disabilities (LD) and
      their participation in college freshman athletics. Although the changes agreed
      upon in the consent decree should have wide-ranging ramifications generally in
      favor of students with LD, the more subjective nature of these changes opens the
      door for inevitable inconsistencies, biases, and possible abuses. In addition,
      larger issues remain unresolved, including (a) the NCAA's denial that is covered
      by the Americans with Disabilities Act, (b) the inconclusive status of whether
      college athletics is a major life activity, (c) the NCAA acting as a de facto
      national school board without rigorous research for setting policy on an informed
      basis, and (d) the lack of serious initiative on the part of the NCAA to take on
      a more supportive role in educational reform.

PMID- 15508477
TI  - Review or regress...

PMID- 15508478
TI  - The identity crisis--or "What you have always wanted to know about AAIH, ABIH,
      ACGIH and AIHA, but were too confused to ask".
AB  - Many Industrial Hygienists are confused about the respective roles and
      relationships of the American Academy of Industrial Hygiene, the American Board
      of Industrial Hygiene, the American Conference of Governmental Industrial
      Hygienists and the American Industrial Hygiene Association. The number of
      Industrial Hygienists in this country is relatively small. As individuals gain
      experience and stature in the field, they often become actively involved in
      leadership roles in several of these organizations. This may tend to be confusing
      to some. Some Industrial Hygienists, especially those who are new to the field,
      have not become actively involved in any of these organizations because they are
      unclear about their eligibility for membership or who to contact for information.

PMID- 15508479
TI  - Are you carrying "hazardous cargo" when you fly???

PMID- 15508480
TI  - Aerosol generation to simulate specific industrial fine particle effluents.
AB  - Techniques were developed for generating large quantities of fine particle metal
      oxide aerosols. The aerosols were generated by burning flammable solutions
      containing appropriate soluble compounds (nitrates, for example) of the desired
      elements. In the flame these compounds generally decomposed to oxides. The
      generated aerosol flow rates were as high as 42 m3 per minute (1500 cfm); the
      mass concentrations were as high as 16.8 g per m3 at STP. For most aerosols the
      particle concentrations were of the order of 10(9) particles per cm3. Electron
      microscopic pictures (SEM and TEM) of precipitated particles show that many of
      the larger particles (20 microm) are hollow and that the smaller particles (0.01
      microm) are aggregated. Specific aerosols were generated to simulate the fine
      particulate effluents generated by combustion of pulverized coal (electricity
      generation) electric arc and basic oxygen furnaces (iron and steel production)
      and zinc smelters. Methods were developed to vary the sulfur dioxide
      concentration and the electrical resistivities of the simulants for coal
      combustion.

PMID- 15508481
TI  - Beryllium sampling methods.
AB  - Three sampling methods for airborne beryllium are compared to validate
      observations made in a 1973 National Institute for Occupational Safety and Health
      (NIOSH) industrywide study of the beryllium industry which indicated that, in
      general, the three methods yielded different results for samples taken in the
      same environment. Under NIOSH contract a beryllium production facility was
      sampled in 1974 by the Atomic Energy Commission (AEC) personal total and personal
      respirable sampling methods over a period of one year. All samples were analyzed
      by atomic absorption spectroscopy. Statistical analysis of the resulting data by
      NIOSH confirms the observations made in the 1973 study that samples collected by
      the three methods produced different results. No reliable relationship was found
      to exist which would permit conversion of the result obtained by one method to a
      result obtained by either of the alternate methods. It appears that, in general,
      for large numbers of samples taken under the same sampling conditions, the values
      determined by the personal respirable sampling method will be lower than those
      obtained by the AEC method and the values determined by the personal total
      sampling method will be greater.

PMID- 15508482
TI  - Sampling and analytical determination of airborne tetramethyl and ethylene
      thiourea.
AB  - Tetramethyl and ethylene thiourea are collected from air using midget impingers
      containing 15 mL water. Ethylene thiourea may also be collected from air using
      PVC or cellulose ester membrane filters which are then extracted with water.
      Pentacyanoamineferrate reagent is added to the filter-extract or to the impinger
      contents to form a colored coordination complex. The absorbance of the solution
      is measured spectrophotometrically at 590 nm, and the unknown concentration of
      tetramethyl or ethylene thiourea samples is determined from calibration curves.
      The detection limit is 0.75 microg/sample for ethylene thiourea and 3
      microg/sample for tetramethyl thiourea. Experimental results indicate that this
      method can be used as a general analytical method for the analysis of other
      thiourea-derived compounds.

PMID- 15508483
TI  - Normal chromium levels in urine and blood of Japanese subjects determined by
      direct flameless atomic absorption spectrophotometry, and valency of chromium in
      urine after exposure to hexavalent chromium.
AB  - Two hundred and thirty one urine and 20 blood samples of Japanese subjects from 4
      geographic areas without known chromium pollution were assayed for chromium by
      direct flameless atomic absorption spectrophotometry. Normal chromium level in
      urine of Japanese subjects was 0.41 microg/L on an average. Urine level was less
      than 0.8 microg/L for all age and sex groups. Chromium levels in 2 hour urines
      did not correlate with those in 24 hours urine. Blood level of chromium was 2.9
      ng/mL. A rabbit given an oral administration of 100 mg hexavalent chromium
      excreted 8.2 mg in 15 days after administration. No hexavalent chromium could be
      detected in urine. Ninety percent of the urinary excretion occurred within 2 days
      of administration.

PMID- 15508484
TI  - The Medical Data Base System of Owens-Corning Fiberglas Corporation.
AB  - The Medical Data Base System provides a mechanism for correlating industrial
      hygiene survey data with specific jobs and with the medical records of the
      individual employee. An occupational survey groups jobs by departments or by
      location according to potential exposures. Results of industrial hygiene surveys
      are correlated with the occupational survey to assign exposures. Results of pre
      placement health examinations, given to every employee and periodic examinations,
      given to those employees who are potentially exposed to harmful chemical or
      physical agents in their work environment, form the Medical Records File.
      Development of the data collection and storage phase of this system was completed
      in 1972, and the system was implemented at that time. The retrieval/analysis
      phase of the system is currently under development. Although the present data
      base does not provide an adequate basis for true epidemiological studies, some
      trial evaluations have been completed successfully.

PMID- 15508485
TI  - Age effect hearing levels for a black nonindustrial noise exposed population
      (NINEP).
AB  - A nonindustrial noise exposed population (NINEP) that describes the age effects
      for a black male and female population has been established. The mean hearing
      threshold levels for the black NINEP are significantly lower (better hearing)
      than the previously established mean HTLs for a white NINEP when compared by sex.
      The availability of the black NINEP now makes it possible to more accurately
      evaluate a typical industrial noise exposed population (INEP).

PMID- 15508486
TI  - Detection of mercury in air in the presence of chlorine and water vapor.
AB  - Evidence is presented that low concentrations of mercury and chlorine vapor in
      air form reaction products. At constant mercury concentration the rate of
      formation increases with chlorine concentration and relative humidity. The
      mercury-chlorine compound as well as the vapor of elemental mercury are absorbed
      by Hopcalite or by KMnO4-H2SO4 scrubber solution. The compound can be separated
      from mercury vapor by its absorption in polyurethane or by filtration by means of
      Millipore aerosol membranes.

PMID- 15508487
TI  - Historical aspects of industrial hygiene--II. Silicosis.
AB  - The extension of knowledge about silicosis, one of civilization's oldest known
      occupational diseases, is traced from antiquity to the twentieth century. In the
      past, silicosis was widely misunderstood and inadequately defined. As silicosis
      became widespread and concomitant with industrial and technological growth and as
      the numbers of workers at risk increased, new interest generated new information,
      and new concepts of control and prevention. Today, although we possess the
      significant medical and technical knowledge to prevent silicosis, there has been
      a failure to eradicate the disease.

PMID- 15508488
TI  - Management of health and safety in carcinogenesis bioassay programs.
AB  - Working with proven or potential chemical carcinogens on a routine basis presents
      complex safety and health problems. These are compounded when a number of
      laboratories under separate managements are brought together under a centrally
      supervised study. This paper presents the types of hazards encountered in such a
      program and describes the approach used in its overall management. Significant
      improvements in worker health and safety are being achieved through a centrally
      coordinated system of self-assessments, hazard surveys, facility monitoring, and
      chemical control evaluations.

PMID- 15508489
TI  - An apparatus for generation of vapors from liquids of low volatility for use in
      inhalation toxicity studies.
AB  - While it is usually a simple matter to perform inhalation exposures to vapors
      from low-boiling liquids, inhalation exposures to vapors of high-boiling liquids
      present problems, especially the risk of decomposing the test substance by use of
      excessive heat. This work describes a device for the volatilization of high
      boiling liquids, in a manner suitable for conducting inhalation exposures,
      without requiring heat input, which avoids this difficulty. The device is based
      on counter-current volatilization employing a multi-plate high efficiency
      distillation column. The column is thermostated below ambient temperature, which
      increases stability of operation and flexibility of application.

PMID- 15508490
TI  - Determination of urinary nitrobenzene by the microdiffusion method.
AB  - A simple, sensitive and specific analytical method based on microdiffusion of
      urinary nitrobenzene into a nitrating mixture and its subsequent determination by
      the butanone method is described in this paper. The method is sensitive to detect
      0.2 mg/L of urinary nitrobenzene.

PMID- 15508491
TI  - Dialkylnitrosamines in elastomers.
AB  - Accelerators and stabilizers used in natural rubber and many types of synthetic
      rubber are often derived from dialkylamines. It has been found that raw polymers,
      compounded uncured elastomers, and cured rubber parts containing these
      dialkylamino compounds emit low concentrations of the corresponding
      dialkylnitrosamine (R2N-N = O) when they are heated. Exposure of operators
      working with these materials can be reduced below a level of 50 parts per
      trillion by volume in air by use of ventilation velocities of about 50 ft/min.
      around the operation. The analytical method is described.

PMID- 15508492
TI  - A conveniently constructed dynamic calibration system.
AB  - Calibration of field equipment is a necessary part of industrial hygiene.
      Instruments such as combustible gas indicators and indicator tubes need to be
      checked to assure that proper results can be obtained from their readings. A
      laboratory may want to check the ability of charcoal or silica gel to collect
      solvent vapors. Static systems may be used to check these values, however, static
      systems have their troublesome limitations. A convenient dynamic calibration
      system is described below.

PMID- 15508493
TI  - Regarding evaluation of zinc protoporphyrin.

PMID- 15508494
TI  - How do you think the brain works?

PMID- 15508495
TI  - Confronting reality.

PMID- 15508496
TI  - Editorial: A strategy for the surveillance of antimicrobial resistance in
      Australia.

PMID- 15508497
TI  - Strategy for antimicrobial resistance surveillance in Australia.

PMID- 15508498
TI  - Tuberculosis notifications in Australia, 2002.
AB  - In 2002, there were 1,028 cases of tuberculosis (TB) reported to the National
      Notifiable Disease Surveillance System, of which 997 were new cases, 30 were
      relapses and 1 unknown. The incidence rate of TB in Australia in 2002 was 5.2
      cases per 100,000 population. The highest incidence of TB was reported in people
      born overseas (20.2 cases per 100,000 population), followed by Indigenous
      Australians (8.5 cases per 100,000 population). By contrast, the incidence rate
      of TB in the nonIndigenous Australian-born population was 1.1 cases per 100,000
      population. This pattern of TB incidence rates amongst the sub-populations of
      Australia has been observed for over 10 years. The rates were evaluated against
      the performance indicators set by the National Tuberculosis Advisory Committee to
      ensure that Australia's record of TB control is maintained and improved.

PMID- 15508499
TI  - Tuberculosis in Australia: bacteriologically confirmed cases and drug resistance,
      2002: a report of the Australian Mycobacterium Reference Laboratory Network.
AB  - The Australian Mycobacterium Reference Laboratory Network collected and analysed
      laboratory data on new cases of disease caused by Mycobacterium tuberculosis
      complex in the year 2002. A total of 712 cases were identified by bacteriology,
      representing an annual reporting rate of 3.6 cases of laboratory-confirmed
      tuberculosis per 100,000 population. The most commonly encountered culture
      positive specimens were sputum (n=325), lymph node (n=142) and bronchoscopy
      (n=100). Smears containing acid fast bacilli were present in sputum (53.2%),
      bronchoscopy (37.9%) and lymph node (21.2%). Eight children (male n=3, female
      n=5) under 10 years of age had bacteriologically-confirmed tuberculosis. A total
      of 55 isolates (7.7%) of M. tuberculosis were resistant to at least one of the
      standard anti-tuberculosis agents. Resistance to at least isoniazid and/or
      rifampicin was noted for 53 isolates (7.4%), with multidrug-resistance (MDRTB)
      observed in 12 (1.9%) isolates. Of the 12 MDRTB isolates, eight were from the
      respiratory tract and five were from smear positive specimens. Of the patients
      with drug resistant M. tuberculosis isolates, 51/55 (92.7%) were classified as
      having initial resistance, none had acquired resistance during treatment in
      Australia. The country of birth was known for 54 of 55 such patients; four were
      Australian-born, and 50 (90.9%) had migrated from a total of 17 countries.
      Nucleic acid amplification testing (NAAT) was performed on 139 (19.5%) of the 712
      culture-positive specimens. Of smear positive respiratory specimens, 74/80
      (92.5%) were NAAT positive. For smear negative respiratory specimens, 12/17
      (70.6%) reported a NAAT positive result. Importantly, false-negative NAAT results
      were obtained from 1/16 and 5/64 of smear positive bronchoscopy and sputum
      specimens respectively.

PMID- 15508500
TI  - Invasive pneumococcal disease in Australia, 2002.
AB  - There were 2,271 cases of invasive pneumococcal disease (IPD) notified to the
      National Notifiable Diseases Surveillance System in Australia in 2002; a rate of
      11.5 cases per 100,000 population. The notification rate varied between states
      and territories and by geographical region with the highest rates in the north of
      the country. Invasive pneumococcal disease was reported most frequently in
      children aged less than five years (57.3 per 100,000 population). Enhanced
      surveillance for IPD in 2002 was carried out in all states and territories,
      providing additional data on 1,929 (85%) of all notified cases. Rates of IPD in
      Indigenous Australians were 2.7 times the rate in non-Indigenous Australians. The
      clinical presentation of IPD was most commonly pneumonia (44%) and bacteraemia
      (35%). There were 175 deaths attributed to IPD resulting in an overall case
      fatality rate of 9.2 per cent. Forty-two per cent of all cases had a recognised
      risk factor for IPD. Seventy-five per cent of all pneumococcal isolates serotyped
      were serotypes in the seven-valent conjugate vaccine and 93 per cent were
      serotypes in the 23-valent polysaccharide pneumococcal vaccine. The clinical
      presentation and rates of risk factors varied between Indigenous and non
      Indigenous cases and non-vaccine serotypes occurred more frequently among
      Indigenous children and adults.

PMID- 15508501
TI  - Laboratory surveillance of invasive pneumococcal disease in Australia in 2001 to
      2002--implications for vaccine serotype coverage.
AB  - This paper reports the results of comprehensive laboratory surveillance of
      invasive pneumococcal disease (IPD) in Australia during 2001 and 2002. The 7
      valent conjugate pneumococcal vaccine was introduced for high risk paediatric
      groups, including Indigenous children, in late 2001. Of 1,355 isolates from non
      Indigenous children, 86 per cent belonged to serotypes and 93 per cent to
      serogroups represented in the 7-valent pneumococcal conjugate vaccine. Thirteen
      per cent and 24 per cent of isolates had reduced susceptibility to penicillin and
      erythromycin, respectively and of these, more than 99 per cent belonged to
      serogroups represented in the 7-valent vaccine. Of the 1,504 isolates from non
      Indigenous adults, 96 per cent belonged to serotypes included in the 23-valent
      polysaccharide vaccine; 14 per cent and 15 per cent had reduced susceptibility to
      penicillin and erythromycin, respectively and more than 95 per cent of these
      belonged to serotypes included in the 7-valent conjugate vaccine. In Western
      Australia and the Northern Territory (the only states for which Indigenous status
      was consistently available), there were 29 cases of IPD in Indigenous children,
      of which 21 were due to 7-valent vaccine serotypes in 2001, compared with 24
      cases, including 10 due to vaccine serotypes, in 2002. This represents a
      statistically significant increase in the proportion of total isolates due to non
      vaccine serotypes (chi2 = 3.93, p = 0.048) following the introduction of the 7
      valent conjugate vaccine, principally due to serotypes 7F and 12F. The number of
      episodes due to penicillin resistant isolates decreased from nine in 2001 to two
      in 2002. Ninety per cent of isolates from Indigenous adults were included in the
      23-valent polysaccharide vaccine and six per cent and five per cent had reduced
      susceptibility to penicillin and erythromycin, respectively. Conjugate
      pneumococcal vaccines can be expected to reduce the incidence of IPD due to
      vaccine serotypes in vaccinated children and potentially, their adult contacts.
      It may also impact favourably on the incidence of IPD due to penicillin and
      erythromycin resistant strains. Continued surveillance of both serotype
      distribution and antibiotic susceptibility are required to identify serotype
      replacement by non-vaccine serotypes and to monitor the overall impact of current
      and future vaccine programs on invasive pneumococcal disease in Australia.

PMID- 15508502
TI  - Surveillance of antibiotic resistance in Neisseria gonorrhoeae in the WHO Western
      Pacific Region, 2002.
AB  - The World Health Organization's Western Pacific Region (WHO WPR) long standing
      programme for surveillance of antimicrobial resistance in Neisseria gonorrhoeae,
      GASP, continued in 2002. Seventeen countries contributed data on about 11,500
      gonococci by determining susceptibility patterns using standardised
      methodologies. Resistance to quinolone and penicillin antibiotics remained widely
      dispersed and at historically high levels. Gonococci with decreased
      susceptibility to third generation cephalosporins were again observed in several
      centres. Spectinomycin resistance was infrequently encountered. Control of
      gonorrhoea in the WHO WPR is compromised by the further reduction in options for
      cheap and effective treatment of gonorrhoea.

PMID- 15508503
TI  - Report of the Australian rotavirus surveillance program 2002-03.
AB  - The National Rotavirus Reference Centre, together with collaborating laboratories
      Australia-wide, has conducted rotavirus surveillance since June 1999. This report
      describes the serotypes of rotavirus strains responsible for the hospitalisation
      of children with acute gastroenteritis during the period 1 July 2002 to 30 June
      2003. We examined 573 faecal samples using monoclonal antibody immunoassays,
      reverse transcription-polymerase chain reaction, and polyacrylamide gel analysis.
      For the second consecutive year, serotype G9 strains were the most prevalent type
      nationally (74.7%) and were found in all seven contributing centres. Serotype G1
      strains were the second most prevalent type (11.3%), identified in four of the
      centres. These findings have implications for vaccine development strategies
      which have targeted protection of disease due to serotypes G1-G4.

PMID- 15508504
TI  - Surveillance of viral pathogens in Australia: Rotavirus.
AB  - For many years, a sentinel laboratory system, the Laboratory Virology and
      Serology Reporting Scheme (LabVISE) has been collecting data on viral pathogens
      of public health importance in Australia. This report is one in a series of
      articles focussing on the epidemiology and public health aspects of viruses and
      viral groups under surveillance by LabVISE, which are of current public health
      interest.

PMID- 15508505
TI  - OzFoodNet: enhancing foodborne disease surveillance across Australia: quarterly
      report, 1 July to 30 September 2003.

PMID- 15508506
TI  - Outbreak of Salmonella Potsdam associated with salad dressing at a restaurant.
AB  - Between 27 January and 7 February 2002, 12 cases of Salmonella Potsdam infection
      were notified to NSW Health of which nine were residents of the Hunter Health
      Area. Interviews with two cases notified by two local doctors initiated the
      investigation and revealed exposure to foods from the same restaurant (restaurant
      A). All New South Wales S. Potsdam cases, those accompanying cases to restaurant
      A and people from restaurant A booking lists were interviewed. Of the 34 people
      interviewed, 17 met the case definition. The epidemiological investigation did
      not detect a food source of S. Potsdam infection, however, shell egg-based Caesar
      salad dressing and mayonnaise, and a swab of a cap from a mayonnaise bottle
      collected at restaurant A tested positive for S. Potsdam. Environmental and
      laying hen feed samples from the egg supplier to restaurant A and meat meal, (the
      major component of laying hen feed) tested positive for various Salmonella
      serotypes. The investigation identified problems of inadequate cleaning, time
      temperature abuse, and ignorance of the hazardous nature of raw shell eggs at the
      restaurant level, poor sanitation and a lack of hygiene inspections at the egg
      production level, and problems with cleaning, storage and lack of bacterial
      monitoring of final product at the animal rendering plant. Investigation of 12
      notified cases of Salmonella resulted in public health interventions, which
      likely prevented further cases of foodborne disease due to Salmonella and other
      pathogens in the Hunter Health Area and elsewhere in New South Wales.

PMID- 15508507
TI  - An outbreak of Salmonella typhimurium phage type 4 linked to cold set cheesecake.

PMID- 15508508
TI  - Salmonella typhimurium U290 outbreak linked to a bakery.

PMID- 15508509
TI  - Investigation of two clusters of shiga toxin-producing Escherichia coli cases in
      South Australia.

PMID- 15508510
TI  - Using the national guidelines to manage a meningococcal group C outbreak in a
      Brisbane boarding school--some discretionary judgements are needed.
AB  - The management of an organisational outbreak of meningococcal disease using the
      national Guidelines for the early clinical and public health management of
      meningococcal disease in Australia (the Guidelines), could be considered a
      relatively straightforward task. Nevertheless, discretional judgements are often
      still required by the outbreak control team, as no guidelines can fully cover
      every eventuality. The greatest challenges generated by this outbreak did not
      result from the magnitude of the intervention, but from the difficulties in
      defining the margins of the intervention in the face of heightened community and
      professional concern. Also Public Health decisions and communication strategies
      needed to be responsive to these concerns.

PMID- 15508511
TI  - Reporting of communicable disease conditions under surveillance by the APSU, 1
      January to 30 June 2003.

PMID- 15508512
TI  - Prevention of opportunistic infections in immunosuppressed patients in the
      tropical top end of the Northern Territory.
AB  - The population of the Top End of the Northern Territory has a high incidence of
      several infections of particular significance in the immunosuppressed. The
      following protocol for evaluation and treatment of patients prior to
      immunosuppression was developed in order to reduce the incidence of serious
      opportunistic infections. The infections discussed are Strongyloides stercoralis,
      tuberculosis, scabies, chronic hepatitis B, melioidosis and other bacterial
      infections. We recommend that all patients planned to receive more than 0.5
      mg/kg/day of prednisolone for >14 days, or any more potent immunosuppressive
      drug, be evaluated and treated according to this protocol. Details of the
      rationale, evidence base, and proposed investigations and therapy for such
      patients are discussed.

PMID- 15508513
TI  - A resurgence of congenital rubella in Australia?
AB  - Two infants with congenital rubella defects (congenital rubella syndrome) have
      been reported from Queensland in 2003, after an increase in rubella in that State
      in 2001-2002. The national Measles Control Campaign in 1998 aimed to give measles
      mumps-rubella (MMR) vaccine to all unvaccinated preschoolers and a second dose to
      primary schoolchildren. Following the Campaign no children with congenital
      rubella defects were born to Australian-born mothers during the five years 1998
      to 2002, according to reports to the Australian Paediatric Surveillance Unit.
      However, three imported cases occurred. Broad immunisation coverage and detection
      and vaccination of susceptible women of child-bearing age before they become
      pregnant are necessary to prevent further cases.

PMID- 15508514
TI  - Rubella in Australia: can we explain two recent cases of congenital rubella
      syndrome?

PMID- 15508515
TI  - Identification of Photorhabdus asymbiotica in cases of human infection.

PMID- 15508517
TI  - The National Immunisation Committee.

PMID- 15508516
TI  - Surveillance for neuraminidase inhibitor resistance in human influenza viruses
      from Australia.
AB  - Two hundred and forty-five human influenza A and B viruses isolated in Australia
      between 1996 and 2003 were tested for their sensitivity to the NA inhibitor
      drugs, zanamivir and oseltamivir using a fluorescence-based neuraminidase
      inhibition assay. Based on mean IC50 values, influenza A viruses (with
      neuraminidase subtypes N1 and N2) were more sensitive to both the NA inhibitors
      than were influenza B strains. Influenza A viruses with a N1 subtype and
      influenza B strains both demonstrated a greater sensitivity to zanamivir than to
      oseltamivir carboxylate, whereas influenza A strains with a N2 subtype were more
      susceptible to oseltamivir carboxylate. A comparison of IC50 values for viruses
      isolated before and after the release of the NA inhibitors in Australia, found
      there was no significant difference in the sensitivity of strains to either
      neuraminidase inhibitor and none of the isolates tested showed clinically
      significant resistance.

PMID- 15508518
TI  - Communicable diseases surveillance: Highlights for 3rd quarter, 2003.
AB  - Communicable disease surveillance highlights report on data from various sources,
      including the National Notifiable Diseases Surveillance System (NNDSS) and
      several disease specific surveillance systems that provide regular reports to
      Communicable Diseases Intelligence. These national data collections are
      complemented by intelligence provided by State and Territory communicable disease
      epidemiologists and/or data managers. This additional information has enabled the
      reporting of more informative highlights each quarter.

PMID- 15508519
TI  - Influence of length of food platform on masticatory performance in patients
      missing unilateral mandibular molars with distal extension removable partial
      dentures.
AB  - Reduction of the size of food platform of a distal extension removable partial
      denture has been recommended to decrease functional load on the abutment teeth
      and residual ridges. The purpose of this study was to investigate the influence
      of shortening food platform on masticatory performance. Eight subjects
      unilaterally missing mandibular molars participated in the study. A unilateral
      design was used for the denture framework. The length of the food platform was
      changed as follows. Initially, (A) was adjusted so that the distal end of the
      platform was in accordance with the distal end of maxillary second molar. Next,
      the platform was shortened successively to 15 mm (B) and 10 mm (C). Subjects were
      asked to masticate 2-colored wax cubes to evaluate masticatory performance.
      Mixing Ability Index was calculated from the color mixture and the form of
      masticated cubes. Repeated measures one-way ANOVA indicated significant
      difference of Mixing Ability Index among platforms (P < 0.0001). The Dunnett's
      test indicated no significant difference between A (1.27 +/- 0.29) and B (1.36 +/
      0.29), and a significant difference between A and C (0.89 +/- 0.30), (P <
      0.001). Masticatory performance decreased significantly when the length of food
      platform was shortened to 10 mm.

PMID- 15508520
TI  - Case-control association study of human netrin G1 gene in Japanese schizophrenia.
AB  - The exact etiology of schizophrenia remains undetermined but accumulating
      evidence suggests that disturbances in neurodevelopment may represent one
      contributory factor. Netrin G1, a recently cloned gene from the mouse, has been
      shown to play a potential role in the formation of neural circuitry. To determine
      whether this gene is involved in the development of psychosis, we performed a
      genetic association study of human netrin G1 gene in schizophrenia. First, we
      determined the human genomic structure of netrin G1 by direct comparisons between
      cDNA and genome sequences, and by database searches. For the subsequent
      examination of heterozygosity, we selected 10 single nucleotide polymorphisms
      (SNPs) for an association test in case (n = 180) and control (n = 180) samples.
      Among these SNPs, IVS8-1467C>T showed significant allelic association (nominal P
      = 0.020) with disease. This SNP is located in a haplotype block of approximately
      40 kb and haplotypes in this block also displayed significant association (most
      significant P = 0.017). These findings suggest that netrin G1 or a nearby gene
      may contribute to the overall genetic risk for schizophrenia.

PMID- 15508521
TI  - Identification of hydroxyapatite deposits in the smooth muscle cells and ganglion
      cells of autopsied small intestines.
AB  - We have studied the deposition of calcium salts in the autopsied intestines which
      have not been described previously as far as we were able to determine. In order
      to clarify the incidence, predisposing conditions, mineral compositions of the
      deposited materials and clinical significance of this phenomenon, we examined 76
      cases of consecutive autopsied small intestines by von Kossa's staining.
      Deposited calcium salts were further examined by electron microscopically, energy
      dispersive X-ray spectroscope and electron diffraction analysis. Deposition of
      calcium salts was observed in the small intestines of 13 cases. Among them, 10
      cases were accompanied by hypercalcemia. Deposition of calcium salts was mainly
      observed in smooth muscle cells of the proper muscle layers and ganglion cells of
      the Auerbach's myenteric plexus. Intestinal calcinosis was frequently accompanied
      by deposition of calcium salts in the proper muscle layers of esophagus and large
      intestine, renal tubules and cardiac myocardial cells. Electron microscopically,
      the calcium salts were identified as needle-shaped crystals and located on the
      surface of the extracellular-collagen bundles, in the cytoplasm, mitochondria and
      nucleus of the smooth muscles cells. Energy-dispersive X-ray spectroscope and
      electron diffraction analysis suggested the deposited calcium salts as
      hydroxyapatite. Two patients among the six cases with moderate to severe calcium
      deposition showed clinical manifestation of paralytic ileus. In conclusion,
      intestinal calcinosis was frequently observed mostly associated with
      hypercalcemia. Calcium salts of hydroxyapatite were deposited to the smooth
      muscle cells and the Auerbach's myenteric plexus of the muscular layer.
      Deposition of calcium salts might occasionally causes the paralytic ileus but
      clinical significance of this lesion requires further examination.

PMID- 15508522
TI  - Patient's perception of location, form and size in case of cavity preparation.
AB  - The aim of the present study was to clarify the difference between the
      imagination of patients and the reality in regard to the location, the form and
      the size of the cavity in case of cavity preparation for dental restoration.
      Firstly, we manufactured the dummy dentition for simulated cavity preparation and
      the operator intra-orally prepared a cavity on the dummy dentition in subject to
      confirm its validity. Then, 5 operators intra-orally prepared prescribed cavities
      at the both sides of maxillary first molars on the dummy dentition in every one
      of 5 subjects with masking. We compared the location, the form and the area of
      these prepared cavities with those imagined by subjects, respectively. In 58% of
      cases, the subjects could accurately recognize the location of prepared teeth.
      And 34% of cases also determined the Class of cavity form. The imagined area was
      larger than the actual area and the difference was statistically significant (p <
      0.001). These results suggested that the perception of the patients regarding the
      location and the form of the prepared cavity was inaccurate during cavity
      preparation and patients tended to overestimate amounts of removed tooth
      substance.

PMID- 15508523
TI  - Development and possible clinical use of antagonists for PDGF and TGF-beta.
AB  - Platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF
      beta) are examples of signaling molecules which control the growth, survival
      motility and differentiation of cells. PDGF stimulates the growth mainly of
      connective tissue cells, whereas TGF-beta inhibits the growth of most cell types.
      PDGF and TGF-beta exert their cellular effects by binding to receptors equipped
      with tyrosine and serine/threonine kinase activities, respectively. Both factors
      have important roles e.g. during the embryonal development and in wound healing.
      Overactivity of PDGF or PDGF receptors contributes to the development of certain
      diseases characterized by excessive cell growth including fibrotic disorders,
      atherosclerosis and malignancies. Overactivity of TGF-beta also contributes to
      fibrotic conditions, since TGF-beta promotes accumulation of extracellular matrix
      molecules. In cancer, TGF-beta is initially a tumor suppressor due to its ability
      to inhibit cell growth, however, at later stages of tumor progression TGF-beta
      has tumor promoting activity by enhancing the invasive properties of tumor cells
      and by suppressing the immune system and promoting angiogenesis. The involvement
      of PDGF in TGF-beta in serious diseases makes clinically useful antagonists
      highly desirable. A low molecular weight receptor kinase inhibitor of the PDGF
      receptor kinase is now tested clinically, and TGF-beta antagonists are under
      development. The present review discusses the development and possible clinical
      use of antagonsts for PDGF and TGF-beta.

PMID- 15508524
TI  - Bystander cells and prognosis in Hodgkin lymphoma. Review based on a doctoral
      thesis.
AB  - Hodgkin lymphoma (HL) is characterised histologically by a minority of malignant
      Hodgkin and Reed-Sternberg (HRS) cells surrounded by benign cells, and clinically
      by a relatively good prognosis. The treatment, however, leads to a risk of
      serious side effects. Knowledge about the biology of the disease, particularly
      the interaction between the HRS cells and the surrounding cells, is essential in
      order to improve diagnosis and treatment. HL patients with abundant eosinophils
      in the tumours have a poor prognosis, therefore the eosinophil derived protein
      eosinophil cationic protein (ECP) was studied. Serum-ECP (S-ECP) was elevated in
      most HL patients. It correlated to number of tumour eosinophils, nodular
      sclerosis (NS) histology, and the negative prognostic factors high erythrocyte
      sedimentation rate (ESR) and blood leukocyte count (WBC). A polymorphism in the
      ECP gene (434(G>C)) was identified and the 434GG genotype correlated to NS
      histology and high ESR. The poor prognosis in patients with abundant eosinophils
      in the tumours has been proposed to depend on HRS cell stimulation by the
      eosinophils via a CD30 ligand (CD30L)-CD30 interaction. However, CD30L mRNA and
      protein were detected in mast cells and the predominant CD30L expressing cell in
      HL is the mast cell. Mast cells were shown to stimulate HRS cell lines via CD30L
      CD30 interaction. The number of mast cells in HL tumours correlated to worse
      relapse-free survival, NS histology, high WBC, and low blood haemoglobin.
      Survival in patients with early and intermediate stage HL, diagnosed between 1985
      and 1992, was generally favourable and comparatively limited treatment was
      sufficient to produce acceptable results for most stages. The majority of
      relapses could be salvaged. Patients treated with a short course of chemotherapy
      and radiotherapy had an excellent outcome. In conclusion prognosis is favourable
      in early and intermediate stages and there are possibilities for further
      improvements based on the fact that mast cells and eosinophils affect the biology
      and prognosis of HL.

PMID- 15508526
TI  - Mast cells in testicular lesions.
AB  - The study was performed on orchidectomized tissue and testicular biopsies sent
      for histopathological examination which included; 9 cases of orchitis, 6 pyocele,
      9 haematocele, 13 seminomas, 5 embryonal cell carcinoma, 2 teratocarcinoma, 2
      lymphoma, 4 yolk sac tumor, 17 infertility lesions and 6 normal. Toluidine blue
      stained sections were examined under high power magnification (hpm) and the
      number of mast cell present in 10 consecutive fields was counted. There was a
      considerable variation in the number and distribution of mast cells in various
      testicular lesions. Mast cells were observed mainly in the areas of inflammatory
      infiltrate, granulation tissue and immature fibrous tissue. In infertility,
      interstitium and tubular walls were the areas of predilection for the presence of
      mast cells. The highest number of mast cells was noted in infertility (23/hpm),
      compared to inflammatory/reactive lesions (19/hpm) and testicular neoplasms
      (2/hpm). The highest and the lowest mast cell concentration were observed in
      infertility and testicular tumours compared to inflammatory/reactive lesions,
      respectively. The role of mast cells in the pathogenesis of infertility and
      testicular tumourogenesis requires further investigation.

PMID- 15508525
TI  - What type of information do parents need after being discharged directly from the
      delivery ward?
AB  - Early discharge normally means that mother and infant are discharged from the
      hospital between six hours and three days after delivery. Early discharge with
      home-visits after normal delivery was introduced at Uppsala University Hospital
      in 1990. Seventeen percent of the women who gave birth in 2003 in Uppsala used
      the home-care option as an alternative to postnatal care at the hospital. The
      home-visiting midwives use a checklist to give and gain information about the
      health of the child and mother and about how breast-feeding is going. The purpose
      of this study was to examine the parents' need of information after early
      discharge after delivery and to compare their needs with the information given
      according to the checklist for home-visits. Forty-two couples completed the
      study. They were asked to formulate five questions to the midwife at the home
      visit. After the questions were gathered, a content-analysis was done. Three
      different main groups were identified: questions concerning 1) the child (68%)
      such as hygiene, bowel movements, burping, vomiting, eating, sleeping and
      sneezing 2) breast-feeding (21%) questions were asked about position while breast
      feeding, nipples and amount of milk 3) the mother (11%) questions concerned
      afterpains, stitches, eating and drinking. The results show that the checklist
      worked sufficiently well as a work tool, but can be adjusted further according to
      the parents' need. This study shows that they needed more information about the
      care of the infant, primarily concerning hygiene.

PMID- 15508527
TI  - Cystatin C vs creatinine as markers of renal function in patients on digoxin
      treatment.
AB  - BACKGROUND: The kidney function is a major determinant of the serum concentration
      of digoxin as this drug is mainly eliminated unchanged through the kidneys. Since
      digoxin is widely prescribed among the elderly, and the glomerular filtration
      rate (GFR) declines with age, it is important that the clinician takes the
      patient's GFR into account when prescribing digoxin. Serum cystatin C has been
      suggested to be superior to creatinine for estimation of GFR, which may have
      relevance for the optimization of treatment with digoxin. METHODS: To evaluate
      which of the two GFR markers serum creatinine and serum cystatin C that best
      correlates with serum digoxin, we compared the serum levels of digoxin with the
      serum levels of creatinine and cystatin C in 149 patients on therapeutic drug
      monitoring of digoxin at our hospital. RESULTS: Overall, there was a stronger
      correlation between serum digoxin concentrations and cystatin C (p=0.00001) as
      compared to creatinine (p= 0.00003). Interestingly, of the patients with a serum
      digoxin concentration > or = 1.5 nmol/L, 29% had a serum creatinine level within
      normal limits, as compared to 20% with normal cystatin C levels. CONCLUSIONS: In
      this study, serum cystatin C correlated better to serum digoxin than did serum
      creatinine. With improved GFR monitoring, digoxin concentrations should be better
      controlled.

PMID- 15508528
TI  - Three cases of malacoplakia of the gallbladder.
AB  - Malacoplakia is a granulomatous disease with a histiocytic infiltrate containing
      calcified bodies called Michaelis-Gutmann bodies considered to represent an
      abnormal response to infection involving defective lysosomes and abnormal
      microtubular assembly. The disease most frequently involves urinary and genital
      tracts, but has also been described from most organs. Reports from the
      gallbladder are extremely rare and as it might simulate specific infection,
      parasitic infestation as well as malignancy it is of importance for the surgeon
      and pathologist to be aware of the entity. In this article we present three cases
      of malacoplakia of the gallbladder, a rare disease in this location.

PMID- 15508529
TI  - Scrotum-like protrusion of lipoma arising from the proximal thigh--report of two
      cases.
AB  - We report two cases of large lipomas arising from the proximal thigh with an
      extremely uncommon shape. The tumors were elastic soft and movable. MRI
      examination revealed both tumors with high signal intensity as fatty tissue on
      both T1 and T2-weighted images. Needle biopsy of the specimens revealed lipoma.
      Marginal excision was carried out for both cases because of the patients'
      discomfort. No recurrence was found three and five years after surgery,
      respectively.

PMID- 15508530
TI  - HRSA reports HIV/AIDS programs are slowing spread of disease.

PMID- 15508531
TI  - Osteoporosis management: out of subspecialty practice and into primary care.

PMID- 15508532
TI  - The continuity of care record.

PMID- 15508533
TI  - Night sweats are commonly vasomotor symptoms.

PMID- 15508534
TI  - Potential interaction between soy milk and warfarin.

PMID- 15508535
TI  - Effectiveness of condoms in reducing heterosexual transmission of HIV.

PMID- 15508536
TI  - Drug treatments for patients with dysthymia.

PMID- 15508537
TI  - Optimal dosage of tricyclic antidepressants.

PMID- 15508538
TI  - Epstein-Barr virus infectious mononucleosis.
AB  - Infectious mononucleosis should be suspected in patients 10 to 30 years of age
      who present with sore throat and significant fatigue, palatal petechiae,
      posterior cervical or auricular adenopathy, marked adenopathy, or inguinal
      adenopathy. An atypical lymphocytosis of at least 20 percent or atypical
      lymphocytosis of at least 10 percent plus lymphocytosis of at least 50 percent
      strongly supports the diagnosis, as does a positive heterophile antibody test.
      False-negative results of heterophile antibody tests are relatively common early
      in the course of infection. Patients with negative results may have another
      infection, such as toxoplasmosis, streptococcal infection, cytomegalovirus
      infection, or another viral infection. Symptomatic treatment, the mainstay of
      care, includes adequate hydration, analgesics, antipyretics, and adequate rest.
      Bed rest should not be enforced, and the patient's energy level should guide
      activity. Corticosteroids, acyclovir, and antihistamines are not recommended for
      routine treatment of infectious mononucleosis, although corticosteroids may
      benefit patients with respiratory compromise or severe pharyngeal edema. Patients
      with infectious mononucleosis should be withdrawn from contact or collision
      sports for at least four weeks after the onset of symptoms. Fatigue, myalgias,
      and need for sleep may persist for several months after the acute infection has
      resolved.

PMID- 15508539
TI  - Information from your family doctor. Things to know about infectious
      mononucleosis.

PMID- 15508540
TI  - Pharmacologic prevention of osteoporotic fractures.
AB  - Osteoporosis is characterized by low bone mineral density and a deterioration in
      the microarchitecture of bone that increases its susceptibility to fracture. The
      World Health Organization defines osteoporosis as a bone mineral density that is
      2.5 standard deviations or more below the reference mean for healthy, young white
      women. The prevalence of osteoporosis in black women is one half that in white
      and Hispanic women. In white women 50 years and older, the risk of osteoporotic
      fracture is nearly 40 percent over their remaining lifetime. Of the drugs that
      have been approved for the prevention or treatment of osteoporosis, the
      bisphosphonates (risedronate and alendronate) are most effective in reducing the
      risk of vertebral and nonvertebral fractures. Risedronate has been shown to
      reduce fracture risk within one year in postmenopausal women with osteoporosis
      and in patients with glucocorticoid-induced osteoporosis. Hormone therapy reduces
      fracture risk, but the benefits may not outweigh the reported risks.
      Teriparatide, a recombinant human parathyroid hormone, reduces the risk of new
      fractures and is indicated for use in patients with severe osteoporosis.
      Raloxifene has been shown to lower the incidence of vertebral fractures in women
      with osteoporosis. Salmon calcitonin is reserved for use in patients who cannot
      tolerate bisphosphonates or hormone therapy.

PMID- 15508541
TI  - Blunt trauma in pregnancy.
AB  - Trauma is the most common cause of nonobstetric death among pregnant women in the
      United States. Motor vehicle crashes, domestic violence, and falls are the most
      common causes of blunt trauma during pregnancy. All pregnant patients with
      traumatic injury should be assessed formally in a medical setting because
      placental abruption can have dire fetal consequences and can present with few or
      no symptoms. Evaluation and treatment are the same as for nonpregnant patients,
      except that the uterus should be shifted off the great vessels. After initial
      stabilization, management includes electronic fetal monitoring, ultrasonography,
      and laboratory studies. Electronic fetal monitoring currently is the most
      accurate measure of fetal status after trauma, although the optimal duration of
      monitoring has not been established. Prevention of trauma through proper seat
      belt use during pregnancy and recognition of domestic violence during prenatal
      care is important.

PMID- 15508542
TI  - Information from your family doctor. Seat belt use during pregnancy.

PMID- 15508543
TI  - Management of acute nasal fractures.
AB  - In cases of facial trauma, nasal fractures account for approximately 40 percent
      of bone injuries. Treatment in the primary care setting begins with evaluating
      the injury, taking an accurate history of the situation in which the injury
      occurred, and ascertaining how the face and nose appeared and functioned before
      the injury occurred. Serious injuries should be treated, then nasal inspection
      and palpation may be performed to assess for airway patency, mucosal laceration,
      and septal deformity. A thorough examination of the nose and surrounding
      structures, including the orbits, mandible, and cervical spine, should be
      completed. Imaging studies are necessary for facial or mandibular fractures.
      Patients with septal hematomas, cerebrospinal fluid rhinorrhea, malocclusion, or
      extraocular movement defects should be referred to a subspecialist. Treatment in
      the primary care setting consists of evaluation, pain and infection management,
      minimal debridement and, when the physician is appropriately trained, closed
      reduction. If an immediate referral is not indicated, close follow-up, possibly
      with a subspecialist, should be arranged within three to five days after the
      injury.

PMID- 15508544
TI  - Screening for dementia.

PMID- 15508545
TI  - What is the best antiviral agent for influenza infection?

PMID- 15508546
TI  - Intestinal obstruction in an octogenarian.

PMID- 15508547
TI  - Information from your family doctor. Flu and colds.

PMID- 15508548
TI  - Information from your family doctor. Flu vaccinations.

PMID- 15508549
TI  - Information from your family doctor. Antibiotics: when they can and can't help.

PMID- 15508550
TI  - Get out the demented vote! The right to vote vs. impaired voting capacity, elder
      abuse, and fraud.

PMID- 15508551
TI  - Isolated, ulcerated violaceous nodule on left cheek: purpuric patch noted
      inferior to main lesion.

PMID- 15508552
TI  - Male depression: a review of gender concerns and testosterone therapy.
AB  - Depression, which affects approximately 6 million men in the United States, is
      associated with a high risk of mortality from comorbid medical illnesses and from
      suicide. Evidence suggests that depresssion affects men differently than women,
      and that older men in particular may experience special influences, symptoms, and
      consequences. The causes of late life depression can be divided into
      psychological, social, and biological factors. Special considerations for this
      population include laboratory studies to identify possible secondary medical
      abnormalities that may either accompany or derive from the depressed mood, and
      pharmacologic treatments that have been shown to be more efficacious in aging
      men. Research involving depressed hypogonadal and eugonadal men suggests that
      depressed men may benefit from testosterone augmentation.

PMID- 15508553
TI  - Inflammatory arthropathy: a review of rheumatoid arthritis in older patients.
AB  - Rheumatoid arthritis (RA) is the most common inflammatory synovitis in older
      adults. The primary care physician may see its presentatiion as the late stage of
      a long-term disorder, or alternatively as an elderly-onset disease. These two
      presentations of RA may differ significantly with respect to mode of onset,
      prevalence of associated systemic symptoms (eg, fatigue, weight loss,
      depression), criteria for diagnosis (eg, rheumatoid factor or rheumatoid
      nodules), progression of diseases and functional outcomes. Because RA is
      responsive to treatmentt, and new treatments are available, diagnosis of this
      disorder is imperative. Differential diagnostic possibilities and therapies are
      reviewed, with particular emphasis on the cause and effect of comorbid disease
      such as infection, osteoporosis, and cardiovascular disease.

PMID- 15508554
TI  - Physical activity upper body range-of-motion exercises. Seated arm swing.

PMID- 15508555
TI  - Fever of unknown origin: keys to determining the etiology in older patients.
AB  - In light of improvements in imaging modalities and laboratory tests, fewer cases
      of fever of unknown origin (FUO) are being attributed to infectious causes and
      more are eventually being diagnosed as secondary to noninfectious causes,
      particularly tumors and connective tissue diseases. Older patients with FUO
      usually present with mild, nonspecific, normochromic, and normocytic anemia and
      an elevated erythrocyte sedimentation rate. The history, physical examination,
      and imaging studies are key to making a diagnosis. Although the results of
      laboratory tests are generally nonspecific, such tests are appropriate
      nonetheless. Obtaining repeat blood cultures is mandatory. However, before
      undertaking a diagnostic evaluation of geriatric FUO, it is important to consider
      the patient's overall health. In certain circumstances, it is more important to
      maintain a patient's quality of life than it is to initiate the process of
      identifying and treating a persistent fever. The work-up and treatment should not
      be worse than the disease.

PMID- 15508556
TI  - Screening for and treating male depression.

PMID- 15508557
TI  - Americans drink enough water; consume too much salt, not enough potassium.

PMID- 15508558
TI  - Sharing stories of excellence in teaching.

PMID- 15508559
TI  - Teaching a nursing fundamentals course to first-semester juniors.

PMID- 15508560
TI  - Perspectives of schools of nursing on nursing regulation.
AB  - Nursing programs in 34 jurisdictions were surveyed to discover their perceptions
      of state board of nursing performance. They were asked for their perceptions of
      the adequacy of current regulation, effectiveness of regulation in protecting the
      public, perceptions of board communication methods, and satisfaction with
      services received. Nursing programs were also asked to rate how essential board
      of nursing involvement is in the approval of nursing programs. Programs reported
      too much regulation in the area of education program approval and perceive
      nursing regulation as fairly effective in promoting quality in education,
      responding to health care changes, and responding to innovation in education.

PMID- 15508561
TI  - Using focused reflection and articulation to promote clinical reasoning: an
      evidence-based teaching strategy.
AB  - This research explored the effects of instructing first-semester nursing students
      in the use of focused reflection and articulation to promote clinical reasoning.
      Student volunteers were randomly assigned to four clinical groups. Two groups
      that received instruction in the use of focused reflection and articulation
      scored significantly higher on the practice measure of clinical reasoning,
      accounting for 29 percent of the variance between groups. Once clinical reasoning
      scores were tabulated, the top six and bottom six scorers on clinical reasoning
      were interviewed to identify qualitative differences between students with
      different reasoning levels. Themes from the interviews revealed that those with
      high clinical reasoning reported a high frequency of use of focused reflection
      and articulation, engaged in abstract learning, and were more self-regulated in
      their learning than those who scored low on clinical reasoning. This study
      provides empirical evidence that using instructional methods that focus learners'
      attention on the concrete application of theory in the practicum setting helps
      enhance their reasoning skills.

PMID- 15508562
TI  - Improving learning outcomes: integration of standardized patients & telemedicine
      technology.
AB  - Innovative use of standardized patients (SPs) in a telemedicine environment can
      improve learning outcomes and clinical competencies. This randomized, cross-over
      study examined the relationship of technology-based strategies and the
      improvement of knowledge outcomes and competencies. Results showed that the
      innovative use of SPs and telemedicine, compared to a traditional distance
      learning teaching methodology, significantly improved learning outcomes. In
      addition, there was a significant increase in performance motivation and an
      interesting decrease in student satisfaction that may be linked to the pressure
      of performance-based learning. This article addresses knowledge improvement only.

PMID- 15508563
TI  - Comparing the teaching effectiveness of part-time & full-time clinical nurse
      faculty.
AB  - The purpose of this study was to compare the teaching effectiveness of part-time
      and full-time clinical nursing faculty. Results indicate that students rank part
      time faculty as significantly less effective than full-time faculty on each of
      five categories measured by the Nursing Clinical Teacher Effectiveness Inventory
      and on the overall scale. These results are supported by the finding that there
      is no significant difference between student ratings of teacher effectiveness and
      the self-ratings of the teachers themselves.

PMID- 15508564
TI  - Current use and opinions regarding human patient simulators in nursing education:
      an international survey.
AB  - The human patient simulator (HPS) has recently been introduced as an adjunct
      technology in nursing education. An international survey of nursing schools and
      simulation centers that collaborate with nursing schools and have purchased a
      Medical Education Technologies, Inc. (METI) HPS was undertaken in 2002. Thirty
      four schools of nursing (18 based in universities and 16 based in community
      colleges) and six simulation centers participated in the survey. Information
      gathered from the survey and reported on in this article includes curricular use,
      faculty time and use, student opinions, evaluation, and other uses of the HPS,
      specifically in research and continuing education. The results provide a
      foundation for early use of the HPS in nursing education at all levels.

PMID- 15508565
TI  - Using an eclectic model to educate students about cultural influences on the
      nurse-patient relationship.
AB  - This article describes how the concepts of cultural awareness, cultural
      sensitivity, and cultural competence are integrated into the nursing curriculum
      at Lehman College, City University of New York. A culturally diverse student
      population engaged in lectures, classroom exercises, and clinical experiences in
      order to learn the ideas and imperatives of cultural diversity in nursing care.
      The exercises were problem-based learning experiences guided by a university
      developed model for teaching students to understand cultural diversity. The model
      is derived from Leininger's comparative cultural caring model and Paterson and
      Zderad's humanistic nursing model. By observing differences and similarities
      among diverse cultures, students learned that the assignment of cultural
      attributes is an inexact process and should be organized as hints rather than as
      certainties. Students also learned the importance of integrating cultural
      awareness, cultural sensitivity, and cultural competence into their nursing care.

PMID- 15508566
TI  - Emerging Technologies Center.

PMID- 15508568
TI  - Crossing the road.

PMID- 15508567
TI  - The National Nursing Education Database.

PMID- 15508569
TI  - Ryanodine-induced oppositely directed changes in frequency of spontaneous
      mediator secretion.

PMID- 15508570
TI  - Comparative analysis of the activation of the Elk-1 transcription factor in the
      central nervous system of animals with different learning capacities.

PMID- 15508571
TI  - Effect of the transplanted thymus of hibernating ground squirrels on the age
      related thymus involution in rats.

PMID- 15508572
TI  - Formation of internal lexicon in seven- to ten-year-old children.

PMID- 15508573
TI  - Effect of stress and magnetic field on the heart activity of the Greenland seal
      Pagophilus groenlandicus.

PMID- 15508574
TI  - A new property of the synthetic anxiolytic Selank and its derivatives.

PMID- 15508575
TI  - Nuclear gamma-resonance electron paramagnetic dialysis: implications for
      experimental biology and medicine.

PMID- 15508576
TI  - Study of the effect of acetylcholine on ion currents in single cells of true and
      latent pacemakers of rabbit sinus node using computer simulation.

PMID- 15508577
TI  - Dynamics of vascular growth factors after coronary angioplasty.

PMID- 15508578
TI  - Regularities in the topographic distribution of ganglion cells in the retina of
      some mammals.

PMID- 15508579
TI  - Differential expression of the isoforms of human vascular endothelial growth
      factor and new approaches to therapeutic angiogenesis.

PMID- 15508580
TI  - Effect of meteorological factors on the fluorescence parameters of phytoplankton
      in the surface water layer of a blooming body of water.

PMID- 15508581
TI  - On the activity of the sable embryonic genome at the stage of delayed
      implantation: a cytogenetic study.

PMID- 15508582
TI  - Inhibition of activity of catalase from potato tubers by salicylic and succinic
      acids.

PMID- 15508583
TI  - Symptoms of infection caused by SARS coronavirus in laboratory mice and guinea
      pigs.

PMID- 15508584
TI  - The effects of mutations in the genes of DNA reparation system on the mutability
      of unstable sex-linked alleles of Drosophila melanogaster.

PMID- 15508585
TI  - Differentiation between the ancestral and evolutionarily new polymorphism in
      populations of the superspecies complex of house mice Mus musculus sensu lato.

PMID- 15508586
TI  - Genetic diversity in Siberian crane (Grus leucogeranus) based on mitochondrial
      DNA D-loop polymorphism.

PMID- 15508587
TI  - Feedback regulation of juvenile hormone titer by biogenic amines in
      Drosophilidae.

PMID- 15508588
TI  - Lemmings of Bolshevik Island (the Severnaya Zemlya archipelago) is a relict of
      the last glacial epoch.

PMID- 15508589
TI  - Degradation of bioplastics in natural environment.

PMID- 15508590
TI  - Measurements of carbon balance in permafrost ecosystems: advances and problems.

PMID- 15508591
TI  - The earliest rodents of the genus Tribosphenomys from the Paleocene of Central
      Asia.

PMID- 15508592
TI  - Changes in the pigment composition of Fucus vesiculosus L. and Fucus serratus L.
      from the Barents Sea during prolonged exposure to the dark.

PMID- 15508593
TI  - Resistance of marine macrophytes to oil pollution.

PMID- 15508594
TI  - Soil microarthropods in the feathers of Antarctic birds.

PMID- 15508596
TI  - Prokaryotic cells growth stimulation induced by electromagnetic radiation at a
      frequency of the molecular oxygen absorption spectrum.

PMID- 15508595
TI  - Structure of intercellular contacts is determined by organization of the
      cytoskeleton.

PMID- 15508598
TI  - Two-wavelength method for endoscopic shape measurement by spatial phase-shifting
      speckle-interferometry.
AB  - A two-wavelength method for endoscopic topography reconstruction is introduced
      that can be applied to out-of-plane sensitive electronic-speckle-pattern
      interferometry systems based on rigid endoscope imaging systems. The surface
      measurement is performed by detection of the phase-difference distribution
      affected by a change in the applied laser wavelength. Furthermore, the off-axis
      endoscopic illumination geometry is taken into account by an approximation.
      Experimental results of the characterization of the endoscopic surface
      reconstruction technique and the measurement accuracy obtained are described and
      discussed. Finally, the applicability of the method is demonstrated with results
      from the topographic reconstruction of a free-form surface.

PMID- 15508597
TI  - Bend sensors with direction recognition based on long-period gratings written in
      D-shaped fiber.
AB  - The curvature- or bend-sensing response of long-period gratings (LPGs) UV
      inscribed in D-shaped fiber has been investigated experimentally. Strong fiber
      orientation dependence of the spectral response when such LPGs are subjected to
      bending at different directions has been observed and is shown to form the basis
      for a new class of single-device sensor with vector-sensing capability. Potential
      applications utilizing the linear response and unique bend-orientation
      characteristics of the devices are discussed.

PMID- 15508599
TI  - Instrument for measuring small angles by use of multiple total internal
      reflections in heterodyne interferometry.
AB  - A new instrument for measuring small angles by use of multiple total internal
      reflections in heterodyne interferometry is presented. With this instrument we
      can achieve a small rotation angle only by measuring the variation in phase
      difference between s- and p-polarization states. To improve its sensitivity we
      increase the number of total internal reflections by using two parallelogram
      prisms instead of two right-angle prisms. The angular resolution of the new
      instrument is better than 2.2 x 10(-6) rad over the measurement range -2.12
      degrees < or = theta < or = 2.12 degrees for 20 total-internal reflections. The
      experimental results and the theoretical curve are in good agreement.

PMID- 15508600
TI  - Measurement of small-signal absorption coefficient and absorption cross section
      of collagen for 193-nm excimer laser light and the role of collagen in tissue
      ablation.
AB  - A 193-nm ArF excimer laser transmission was measured at subablative fluence
      through varying strength solutions of dissolved collagen, yielding an absorption
      cross section of 1.14 x 10(-17) cm2 for the peptide bond, which accounts for 96%
      of the total collagen attenuation that is based on additional transmission
      measurements through solutions of isolated constituent amino acids. The measured
      absorption cross sections, in combination with typical corneal tissue
      composition, yield a predicted corneal tissue absorption coefficient of 16,000
      cm(-1). In addition, dry collagen films were prepared and ablation-rate data were
      recorded as a function of laser fluence. Ablation rates were modeled by use of a
      Beer-Lambert blow-off model, incorporating a measured ablation threshold and an
      absorption coefficient that are based on the measured collagen absorption cross
      section and the film bond density. The measured ablation rates and those
      predicted by the model were in very good agreement. The experiments suggest that
      collagen-based absorption coefficients are consistent with predicted corneal
      tissue ablation rates and previously observed dynamic changes in tissue
      properties under ablative conditions.

PMID- 15508601
TI  - Improved emission uniformity from a liquid-jet laser-plasma extreme-ultraviolet
      source.
AB  - Many modern compact soft-x-ray and extreme-ultraviolet (EUV) imaging systems
      operate with small fields of view and therefore benefit from the use of small
      high-brightness sources. Such systems include water-window microscopes and EUV
      lithography tools. We show that the photon losses in such systems can be
      minimized while uniformity of object-plane illumination is maintained by
      controlled scanning of the source. The improved collection efficiency is
      demonstrated both theoretically and experimentally for a scanned laser-plasma
      source compared with static sources. A prospective aerial image microscope and a
      liquid-xenon-jet laser-plasma source are offered as examples of modern imaging
      tools that may benefit from such scanning of the source.

PMID- 15508602
TI  - Performance of the Keck Observatory adaptive-optics system.
AB  - The adaptive-optics (AO) system at the W. M. Keck Observatory is characterized.
      We calculate the error budget of the Keck AO system operating in natural guide
      star mode with a near-infrared imaging camera. The measurement noise and
      bandwidth errors are obtained by modeling the control loops and recording
      residual centroids. Results of sky performance tests are presented: The AO system
      is shown to deliver images with average Strehl ratios of as much as 0.37 at 1.58
      microm when a bright guide star is used and of 0.19 for a magnitude 12 star. The
      images are consistent with the predicted wave-front error based on our error
      budget estimates.

PMID- 15508603
TI  - Quasi-free-space optical coupling between diffraction grating couplers fabricated
      on independent substrates.
AB  - Optical coupling between preferential-order volume diffraction grating couplers
      fabricated on independent substrates is demonstrated. The coupling efficiency
      between gratings is quantified as a function of both grating and waveguide
      fabrication technology and relative angular position of the two substrates. A
      maximum grating-to-grating coupling efficiency of 31% is reported for coupling
      between two nonoptimized, nonfocusing, unpatterned volume grating couplers.

PMID- 15508604
TI  - Design and fabrication of continuous-profile diffractive micro-optical elements
      as a beam splitter.
AB  - An optimization algorithm that combines a rigorous electromagnetic computation
      model with an effective iterative method is utilized to design diffractive micro
      optical elements that exhibit fast convergence and better design quality. The
      design example is a two-dimensional 1-to-2 beam splitter that can symmetrically
      generate two focal lines separated by 80 microm at the observation plane with a
      small angle separation of +/- 16 degrees. Experimental results are presented for
      an element with continuous profiles fabricated into a monocrystalline silicon
      substrate that has a width of 160 microm and a focal length of 140 microm at a
      free-space wavelength of 10.6 microm.

PMID- 15508605
TI  - Programmable select multiwavelength gigahertz Raman soliton pulse generation.
AB  - The generation of programmable multiwavelength pulses based on the self-frequency
      shift of a Raman soliton is demonstrated. The approach produces tunable
      multiwavelength picosecond pulses. Only select multiwavelength signals with a
      tuning range of approximately 50 nm are generated with a repetition rate of 9.95
      GHz at each wavelength channel. A bit error rate (BER) of better than 1 x 10(-9)
      was successfully obtained for all the measured multiwavelength Raman soliton
      pulses. Furthermore, it was found that the signal has an excellent relative
      intensity noise (RIN) of better than -135.5 dBc/Hz. The BER and RIN measurements
      show that the frequency-shifted Raman soliton pulses are promising for use in
      measurement systems, optical gating, signal processing, and wavelength routing
      optical packet networks with the ability to provide 1:1 communication and 1:N
      multicasting.

PMID- 15508606
TI  - Study of the dynamic formation of transmission gratings recorded in photopolymers
      and holographic polymer-dispersed liquid crystals.
AB  - Local and nonlocal models for the diffusion of photopolymers are applied to the
      dynamic formation of transmission gratings recorded in photopolymers and
      holographic polymer-dispersed liquid crystals (H-PDLCs). We retrieve the main
      parameters of H-PDLCs (refractive-index modulation and diffusion coefficient) by
      combining a solution of the one-dimensional diffusion equation and the rigorous
      coupled-wave theory applied to transmission gratings. The rigorous coupled-wave
      theory method provides us with information on higher harmonics of the refractive
      profile (not only on the first harmonic as when the classical Kogelnik theory is
      applied). Measurements concerning the second harmonic validate the modeling.

PMID- 15508607
TI  - Performance of a write-once multilayer optical disk that uses transparent
      recording material with an optical switching layer.
AB  - A volumetric optical disk that has multiple transparent films with optical
      switching layers is used as a recording medium to increase the number of
      recording layers. In the disk the optical switching layer is adapted to reduce
      decay of laser energy and increase reading and recording sensitivity. Well
      defined marks of approximately 100-nm depth can be placed precisely on the
      transparent films by a focused laser beam. Writing and reading of a four-layer
      recordable disk, fabricated by molding and spin bonding, have been demonstrated
      experimentally. The volumetric disk can achieve a high recording capacity with
      conventional optical pickups.

PMID- 15508608
TI  - Characterization of atmospheric aerosols from infrared measurements: simulations,
      testing, and applications.
AB  - An inversion method for the characterization of atmospheric condensed phases from
      infrared (IR) spectra is described. The method is tested with both synthetic IR
      spectra and the spectra of particles that flow in a cryogenic flow tube. The
      method is applied to the IR spectra recorded by the Atmospheric Trace Molecule
      Spectroscopy instrument carried by the Space Shuttle during three missions in
      1992, 1993, and 1994. The volume density and particle size distribution for
      sulfate aerosol are obtained as a function of altitude. The density and size
      distribution of ice particles in several cirrus clouds are also retrieved. The
      probable radius of the ice particles in the high-altitude (10-15-km) cirrus
      clouds is found to be approximately 6-7 microm.

PMID- 15508609
TI  - Numerical simulation of light backscattering by spheres with off-center
      inclusion. Application to the lidar case.
AB  - A Mie backscattering model for spherical particles with off-center inclusion has
      been developed and tested. The program is capable of dealing with size parameter
      values up to approximately 1000, thus allowing one to simulate the optical
      behavior of a large variety of atmospheric aerosols, as well as cloud and
      precipitation particles. On the basis of this model, we simulated the optical
      properties of polydisperse composite atmospheric particles as observed by ground
      based and airborne lidar systems. We have characterized optical properties in
      terms of host and inclusion radii, considering water particles with different
      composition inclusions. The performed modeling provides some insight into the so
      called lidar bright- and dark-band phenomenon.

PMID- 15508610
TI  - Measurements and numerical analysis for femtosecond pulse deformations after
      propagation of hundreds of meters in air with water-vapor absorption lines.
AB  - We have clarified the influences of water-vapor absorption lines in air on
      femtosecond pulse propagations from experimental and theoretical points of view.
      Precise measurements for the femtosecond pulse shapes after propagation of as
      much as 300 m through air have been made in a semiunderground optical testing
      tunnel. We observed the pulse splitting and the enhancement of the pulse
      broadening due to the 100-m propagation in air. The experimental results are in
      good agreement with the theoretical analysis by use of the HITRAN database at the
      edge and the center of the water-vapor absorption regions in air. Measured
      autocorrelation traces are mostly reproduced by those calculated with only the
      real part (dispersion) of the refractive index modulated by water-vapor
      absorption lines in air. This fact enables us to conclude that the pulse
      deformations due to water absorption lines in air are caused mainly by the real
      part (dispersion), not by the imaginary part (absorption), of the refractive
      index of air.

PMID- 15508611
TI  - Imaginary refractive-index effects on desert-aerosol extinction versus
      backscatter relationships at 351 nm: numerical computations and comparison with
      Raman lidar measurements.
AB  - A numerical model is used to investigate the dependence at 351 nm of desert
      aerosol extinction and backscatter coefficients on particle imaginary refractive
      index (mi). Three ranges (-0.005 < or = mi < or = -0.001, -0.01 < or = mi < or = 
      0.001, and -0.02 < or = mi < or = -0.001) are considered, showing that
      backscatter coefficients are reduced as /mi/ increases, whereas extinction
      coefficients are weakly dependent on mi. Numerical results are compared with
      extinction and backscatter coefficients retrieved by elastic Raman lidar
      measurements performed during Saharan dust storms over the Mediterranean Sea. The
      comparison indicates that a range of -0.01 to -0.001 can be representative of
      Saharan dust aerosols and that the nonsphericity of mineral particles must be
      considered.

PMID- 15508612
TI  - Influence of numerical aperture on mode coupling in step-index plastic optical
      fibers.
AB  - Using the power-flow equation, we have examined the state of mode coupling in
      step-index plastic optical fibers with different numerical apertures. Our results
      confirm that the coupling rates vary with the coupling coefficient of the fibers
      as the dominant parameter, especially in the early stage of coupling near the
      input fiber end. However, we show that the fiber's numerical aperture has a
      significant influence on later stages of this process. Consequently, equilibrium
      mode distribution and steady-state distribution are achieved at overall fiber
      lengths that depend on both of these factors. As one of our examples
      demonstrates, it is possible for the coupling length of a high-aperture fiber to
      be similar to that of a low-aperture fiber despite the three-times-larger
      coupling coefficient of the former.

PMID- 15508613
TI  - Simple method for frequency locking of an extended-cavity diode laser.
AB  - We have developed an extended-cavity tunable diode laser system that has a small
      linewidth and a large output power (more than 90% of the free-running power)
      whose operating frequency can be conveniently locked to a transition line of Rb
      atoms. Based on flat-mirror feedback and frequency self-locking and with weak
      feedback, we have achieved a continuous frequency detuning range greater than 900
      MHz and a short-time linewidth stability of better than 0.4%. By using a two-step
      locking procedure we not only can lock the laser frequency but also can detune
      the frequency to any desired value. The locking is quite sturdy and rugged.

PMID- 15508614
TI  - Algorithm for the retrieval of columnar water vapor from hyperspectral remotely
      sensed data.
AB  - A new algorithm for the retrieval of columnar water vapor content is presented.
      The proposed procedure computes the area of the H2O absorption centered about 940
      nm to allow its integrated columnar abundance as well as its density at ground
      level to be assessed. The procedure utilizes the HITRAN 2000 database as the
      source of H2O cross-section spectra. Experimental results were derived from
      radiometrically calibrated hyperspectral images collected by the Airborne Visible
      Infrared Imaging Spectrometer (AVIRIS) sensor over the Cuprite mining district in
      Nevada. Numerical simulations based on the MODTRAN 4 radiative transfer code were
      also employed for investigating the algorithm's performance. An additional
      empirical H2O retrieval procedure was tested by use of data gathered by the VIRS
      200 imaging spectrometer.

PMID- 15508615
TI  - Application of 266-nm and 355-nm Nd:YAG laser radiation for the investigation of
      fuel-rich sooting hydrocarbon flames by raman scattering.
AB  - We describe the use of linear Raman scattering for the investigation of fuel-rich
      sooting flames. In comparison, the frequency-tripled and -quadrupled fundamental
      wavelengths of a Nd:YAG laser have been used as an excitation source for study of
      the applicability of these laser wavelengths for analysis of sooting flames. The
      results obtained show that, for the investigation of strongly sooting flames, 266
      nm excitation is better than 355-nm excitation. Although the entire fluorescence
      intensity of polycyclic aromatic hydrocarbons (PAHs) decreases with rising
      excitation wavelength, there is increased interference with the Raman signals by
      displacement of the spectral region of the Raman signals toward the fluorescence
      maximum of the laser-induced fluorescence emissions. Besides the broadband
      signals of PAHs, narrowband emissions of laser-produced C2 occur in the spectra
      of sooting flames and affect the Raman signals. These C2 emission bands are
      completely depolarized and can be separated by polarization-resolved detection. A
      comparison of the laser-induced fluorescence emissions of an ethylene flame with
      those of a methane flame shows the same spectral features, but the intensity of
      the emissions is larger by a factor of 5 for the ethylene fuel. Using 266-nm
      radiation for Raman signal excitation makes possible measurements in the ethylene
      flame also.

PMID- 15508616
TI  - Irradiation and chlorination effectively reduces Escherichia coli O157:H7
      inoculated on cilantro (Coriandrum sativum) without negatively affecting quality.
AB  - Cilantro (Coriandrum sativum) inoculated with Escherichia coli O157:H7 at levels
      approximating 10(7) CFU/g was dipped in 200 ppm chlorine solution followed by low
      dose gamma irradiation. Samples were plated on tryptic soy agar containing 50
      microg/ml nalidixic acid (TSAN) as well as TSAN plates with two 7-ml layers of
      basal yeast extract agar (TSAN-TAL). Levels of E. coli O157:H7 recovered from
      both types of media were determined over 11 days. Chlorination alone reduced
      counts by just over 1.0 log cycle, whereas irradiation at 1.05 kGy resulted in a
      6.7-log reduction, and a combination of irradiation and chlorination reduced
      counts more than 7 log cycles. Trained panels performed analytical sensory tests
      at time intervals for 14 days to detect changes in yellowing, tip burn, browning,
      black rot, sliminess, off-aroma, and off-flavor. Sensory tests found no
      significant differences among attributes over time or dose in samples irradiated
      at 1.08 to 3.85 kGy. This study showed that combination treatments of
      chlorination and low-dose irradiation can significantly reduce levels of E. coli
      O157:H7 in fresh cilantro while maintaining product quality.

PMID- 15508617
TI  - Effect of simulated spray chilling with chemical solutions on acid-habituated and
      non-acid-habituated Escherichia coli O157:H7 cells attached to beef carcass
      tissue.
AB  - Samples (10 by 20 by 2.5 cm) of beef carcass tissue were inoculated (10(4) to
      10(5) CFU/cm2) with Escherichia coli O157: H7 that was either non-acid habituated
      (prepared by incubating at 15 degrees C for 48 h in inoculated filter-sterilized
      composite [1:1] of hot and cold water meat decontamination runoff fluids, pH
      6.05) or acid habituated (prepared in inoculated water fluids mixed with filter
      sterilized 2% lactic acid [LA] runoff fluids in a proportion of 1/99 [vol/vol],
      pH 4.12). The inoculated surfaces were exposed to conditions simulating carcass
      chilling (- 3 degrees C for 10 h followed by 38 h at 1 degree C). Treatments
      applied to samples (between 0 and 10 h) during chilling included the following:
      (i) no spraying (NT) or spraying (for 30 s every 30 min) with (ii) water, (iii)
      cetylpyridinium chloride (CPC; 0.1 or 0.5%), (iv) ammonium hydroxide (AH; 0.05%),
      (v) lactic acid (LA; 2%), (vi) acidified sodium chlorite (ASC; 0.12%), (vii)
      peroxyacetic acid (PAA; 0.02%), (viii) sodium hydroxide (SH; 0.01%), or (ix)
      sodium hypochlorite (SC; 0.005%) solutions of 4 degrees C. Samples were taken at
      0, 10, 24, 36, and 48 h of the chilling process to determine changes in E. coli
      O157:H7 populations. Phase 1 tested water, SH, PAA, LA, and 0.5% CPC on meat
      inoculated with non-acid-habituated pathogen populations, whereas phase 2 tested
      water, SC, AH, ASC, LA, and 0.1% CPC on meat inoculated with acid- and non-acid
      habituated populations. Reductions in non-acid-habituated E. coli O157:H7
      populations from phase 1 increased in the order NT = water = SH < PAA < LA < CPC.
      Reductions from phase 2 for acid-habituated cells increased in the order NT =
      water = SC < ASC = LA = AH < CPC, whereas on non-acid-habituated cells the order
      observed was NT = water = SC < AH = ASC < LA < CPC. Previous acid habituation of
      E. coli O157:H7 inocula rendered the cells more resistant to the effects of spray
      chilling, especially with acid; however, the trend of reduction remained spray
      chilling with water = non-spray chilling < spray chilling with chemical
      solutions.

PMID- 15508618
TI  - Survival and growth of Escherichia coli O157:H7 in roast beef and salami after
      exposure to an alkaline cleaner.
AB  - Survival and growth of wild-type (EDL 933) and rpoS-deficient (FRIK 816-3)
      strains of Escherichia coli O157:H7 after exposure to an alkaline cleaner for 2
      min and inoculating into roast beef (pH 6.3) and hard salami (pH 4.9) at low
      (0.003 to 0.52 CFU/g) and high (0.69 to 31.5 CFU/g) populations were determined.
      Roast beef was stored at 4 and 12 degrees C; salami was stored at 4, 12, and 20
      degrees C. At 4 degrees C, untreated cells of both strains showed greater
      reductions in populations in salami than in roast beef during a 21-day storage
      period. Populations of treated and untreated cells recovered from roast beef and
      salami stored at 4 degrees C on tryptic soy agar were significantly (P < or =
      0.05) higher than on sorbitol MacConkey agar, indicating that a portion of the
      cells was injured. Treated and untreated cells grew in roast beef at 12 degrees
      C. Growth of treated cells of the FRIK 816-3 strain in roast beef at 12 degrees C
      was significantly slower than that of the EDL 933 strain. Populations of both
      strains decreased at different rates in salami stored at different temperatures
      (20 degrees C > 12 degrees C > 4 degrees C). E. coli O157:H7 strain EDL 933 grew
      more rapidly at 20 degrees C in a slurry (pH 5.97) prepared from stored salami
      (17 days at 20 degrees C) on which Penicillium chrysogenum had grown than in a
      slurry (5.23) prepared from salami showing no mold growth. Within 2 to 3 days,
      populations were ca. 3 log CFU/ml higher in slurry made from infected salami than
      in control salami. Results indicate that treatment of E. coli O157: H7 with an
      alkaline cleaner for 2 min does not impair resuscitation and growth of surviving
      cells in roast beef at 12 degrees C. Cross protection of cells exposed to an
      alkaline cleaner against subsequent stress conditions imposed by roast beef and
      salami stored at 4 degrees C was not evident in either of the test strains.

PMID- 15508619
TI  - Detection and isolation of Escherichia coli with a coding gene for
      enteroaggregative Escherichia coli heat-stable enterotoxin 1 from food and
      comparison with fecal isolates.
AB  - Enteroaggregative Escherichia coli heat-stable enterotoxin 1 (EAST1) was
      originally regarded as a putative enterotoxin of enteroaggregative Escherichia
      coli. Although its etiological role has not yet been elucidated, it has been
      epidemiologically suggested that some strains of E. coli possessing EAST1-coding
      gene (astA) but no other identifiable pathogenic properties comprise a new group
      of diarrhea-associated E. coli (EAST1EC). However, the source of the organisms
      and their prevalence in foods are still obscure. In this study, methods for
      detection of the organisms in foods heavily contaminated with coliforms were
      evaluated and properties of the isolated strains were compared with those of
      fecal strains. Four enrichment methods (brilliant green lactose bile broth, E.
      coli, lauryl tryptose broth, and a combination of brain heart infusion broth and
      tryptone phosphate broth) were evaluated through inspection of 115 samples. PCR
      showed positive results in 26 samples after enrichment with a combination of
      brain heart infusion broth and tryptone phosphate broth, and EAST1EC was
      successfully isolated from 18 samples. Fifteen samples showed a positive reaction
      in the PCR test after enrichment by the other methods, and the organisms were
      isolated from only 10 specimens. The highest prevalence of EAST1EC was found in
      animal products (16 of 54, 29.6%); the organism was rarely found in foods of
      plant origin (2 of 45, 4.4%) or fishery products (1 of 16, 6.3%). Although
      EAST1EC is unexpectedly common in animal products, its potential as a human
      pathogen remains uncertain because the possession of some virulence properties
      differs significantly between strains from fecal specimens and those from foods.
      Some food isolates, however, possess the same characteristics as diarrheal
      isolates do. It is necessary to clarify the pathogenicity of EAST1EC and the
      significance of food as a source of infection.

PMID- 15508620
TI  - Attachment and biofilm formation by Escherichia coli O157:H7 on stainless steel
      as influenced by exopolysaccharide production, nutrient availability, and
      temperature.
AB  - The influence of exopolysaccharide (EPS) production, nutrient availability, and
      temperature on attachment and biofilm formation by Escherichia coli O157:H7
      strains ATCC 43895 (wild type) and 43895-EPS (extensive EPS-producing mutant) on
      stainless steel coupons (SSCs) was investigated. Cells grown on heated lettuce
      juice agar and modified tryptic soy agar were suspended in phosphate-buffered
      saline (PBS). SSCs were immersed in the cell suspension (10(9) CFU/ml) at 4
      degrees C for 24 h. Biofilm formation by cells attached to SSCs as affected by
      immersing in 10% tryptic soy broth (TSB), lettuce juice broth (LJB), and minimal
      salts broth (MSB) at 12 and 22 degrees C was studied. A significantly lower
      number of strain 43895-EPS cells, compared to strain ATCC 43895 cells, attached
      to SSCs during a 24-h incubation (4 degrees C) period in PBS suspension. Neither
      strain formed a biofilm on SSCs subsequently immersed in 10% TSB or LJB, but both
      strains formed biofilms in MSB. Populations of attached cells and planktonic
      cells of strain ATCC 43895 gradually decreased during incubation for 6 days in
      LJB at 22 degrees C, but populations of strain 43895-EPS remained constant for 6
      days at 22 degrees C, indicating that the EPS-producing mutant, compared to the
      wild-type strain, has a higher tolerance to the low-nutrient environment
      presented by LJB. It is concluded that EPS production by E. coli O157:H7 inhibits
      attachment to SSCs and that reduced nutrient availability enhances biofilm
      formation. Biofilms formed under conditions favorable for EPS production may
      protect E. coli O157:H7 against sanitizers used to decontaminate lettuce and
      produce processing environments. Studies are under way to test this hypothesis.

PMID- 15508621
TI  - Survey of yeasts for antagonistic activity against Salmonella Poona in cantaloupe
      juice and wounds in rinds coinfected with phytopathogenic molds.
AB  - Application of yeasts as biocontrol agents to prevent mold decay of fruits and
      vegetables has been described. We examined 10 yeasts for potential antagonistic
      activity against survival and growth of Salmonella Poona in cantaloupe juice and
      decay by Cladosporium cladosporioides and Geotrichum candidum in wounds on
      cantaloupe rind. Cantaloupe juice was inoculated using five schemes: Salmonella
      Poona only (1.10 log CFU/ml), high (3.93 to 5.21 log CFU/ml) or low populations
      (1.79 to 3.26 log CFU/ml) of yeasts only, and Salmonella Poona combined with high
      or low populations of yeasts. High initial populations of Debaryomyces hansenii,
      Pichia guilliermondii, and Pseudozyma sp. were antagonistic to Salmonella Poona
      in cantaloupe juice stored at 20 degrees C for 48 h. Wounds in cantaloupe rinds
      were inoculated with yeast and mold or yeast, mold, and Salmonella Poona, and
      cantaloupes were stored at 4 degrees C for 14 days or 20 degrees C for 7 days.
      The pH of rind tissue inoculated with C. cladosporioides and yeasts increased
      significantly (P < or = 0.05) at 20 degrees C. Wounds that were inoculated with
      P. guilliermondii, together with C. cladosporioides or G. candidum, did not show
      mold growth at 4 and 20 degrees C. Populations of Salmonella Poona (6.40, 7.26,
      and 7.98 log CFU per sample) were lower in wounds coinoculated with G. candidum
      and three of the test yeasts (D. hansenii, P. guilliermondii, and Cryptococcus
      albidus, respectively) compared to coinoculation with G. candidum or the other
      seven yeasts. Candida oleophila and Rhodotorula glutinis showed the most promise
      in reducing the population of Salmonella Poona in wounds in rinds of cantaloupes
      coinoculated with G. candidum and stored at 4 degrees C.

PMID- 15508622
TI  - Effect of nisin in combination with EDTA, sodium lactate, and potassium sorbate
      for reducing Salmonella on whole and fresh-cut cantaloupet.
AB  - Nisin (50 microg/ml), EDTA (0.02 M, disodium salt), sodium lactate (NaL, 2%), and
      potassium sorbate (KS, 0.02%) were tested individually and in various
      combinations as sanitizer treatments for reducing Salmonella on whole and fresh
      cut cantaloupe. Whole cantaloupe and fresh-cut pieces were inoculated with a five
      strain cocktail of Salmonella to give 4.76 +/- 0.23 log CFU/cm2 and 3.42 +/- 0.13
      log CFU/g, respectively. Inoculated whole melons and fresh-cut pieces were stored
      at 5 degrees C for 7 days. Washing treatments were applied to inoculated whole
      melons at days 0, 3, and 7 of storage, and surviving bacterial populations were
      determined. The effect of the washing treatments on transfer of Salmonella to
      fresh-cut pieces prepared immediately after treatment was also determined.
      Directly inoculated fresh-cut pieces were treated at day 0, and surviving
      bacteria were enumerated at days 0, 3, and 7 of storage. The combination
      treatments of nisin-EDTA, nisin-NaL, nisin-KS, NaL-KS, and nisin-NaL-KS all
      resulted in reductions of approximately 3 log CFU/cm2 at day 0 for whole melons.
      When tested alone, all compounds, along with water washes, were ineffective.
      After 3 and 7 days of storage, the five combination washing treatments were less
      effective, resulting in reductions of approximately 2 log CFU/cm2. None of the
      combination treatments completely eliminated transfer of pathogen survivors to
      fresh-cut pieces. The combination treatments nisin-NaL, nisin-KS, NaL-KS, and
      nisin-NaL-KS, but not nisin-EDTA, gave significant (P < 0.05) reductions of
      Salmonella directly inoculated onto fresh-cut pieces. Washing with nisin-NaL-KS
      was significantly (P < 0.05) more effective than the other three combination
      treatments, resulting in a reduction of 1.4 CFU/g. Inhibition by the four
      effective treatments carried over from day 0 through day 7 of storage, with no
      increase in the population of Salmonella on the stored fresh-cut pieces. Sensory
      evaluations indicated that treatment of fresh-cut pieces with nisin-NaL and NaL
      KS, but not nisin-KS or nisin-NaL-KS, were acceptable in terms of appearance,
      odor, and overall acceptability. After the required regulatory approval,
      treatment of whole cantaloupe with nisin in combination with EDTA, NaL, KS, or
      NaL and KS and of fresh-cut pieces with nisin-NaL or NaL-KS could help ensure the
      microbiological safety of fresh-cut cantaloupe.

PMID- 15508623
TI  - Effectiveness of cleaners and sanitizers in killing Salmonella Newport in the gut
      of a free-living nematode, Caenorhabditis elegans.
AB  - Caenorhabditis elegans, a free-living nematode found in soil, has been shown to
      ingest human enteric pathogens, thereby potentially serving as a vector for
      preharvest contamination of fruits and vegetables. A study was undertaken to
      evaluate the efficacy of cleaners and sanitizers in killing Salmonella enterica
      serotype Newport in the gut of C. elegans. Adult worms were fed nalidixic acid
      adapted cells of Escherichia coli OP50 (control) or Salmonella Newport for 24 h,
      washed, placed on paper discs, and incubated at temperatures of 4 or 20 degrees C
      and relative humidities of 33 or 98% for 24 h. Two commercial cleaners (Enforce
      and K Foam Lo) and four sanitizers (2% acetic acid, 2% lactic acid, Sanova, and
      chlorine [50 and 200 microg/ml]) were applied to worms for 0, 2, or 10 min.
      Populations of E. coli and Salmonella Newport (CFU per worm) in untreated and
      treated worms were determined by sonicating worms in 0.1% peptone and surface
      plating suspensions of released cells on tryptic soy agar containing nalidixic
      acid. Populations of Salmonella Newport in worms exposed to 33 or 98% relative
      humidity at 4 degrees or 33% relative humidity at 20 degrees C were significantly
      (P < or = 0.05) lower than the number surviving exposure to 98% relative humidity
      at 20 degrees C. In general, treatment of desiccated worms with cleaners and
      sanitizers was effective in significantly (P < or = 0.05) reducing the number of
      ingested Salmonella Newport. Results indicate that temperature and relative
      humidity influence the survival of Salmonella Newport in the gut of C. elegans,
      and cleaners and sanitizers may not eliminate the pathogen.

PMID- 15508624
TI  - Comparison of four different methods for Salmonella detection in fecal samples of
      porcine origin.
AB  - Performances of four detection methods were evaluated for recovery of Salmonella
      spp. in naturally contaminated fecal specimens of porcine origin. The NMKL 71
      method consisted of enrichment in Rappaport-Vassiliadis broth and plating on
      xylose-lysine-desoxycholate medium, whereas the SP-VG-M002 method relied on a
      Diasalm enrichment followed by streaking on xylose-lysine-tergitol 4 agar (XLT
      4). The VIDAS SLM method was composed of double enrichment in Muller-Kauffmann
      tetrathionate broth and in M broths before processing in a VIDAS device. If the
      results were positive, the VIDAS ICS immunoenrichment was performed and the
      result transferred onto three different selective media. The VIDAS ICS protocol
      is an immunoconcentration step followed by plating on XLT-4. Seventy-eight
      samples were tested with all four methods simultaneously, leading to 34 positive
      samples with at least one method. For this assay, VIDAS SLM revealed 31 positive
      samples (91.2%), whereas the average positive percentage of the three other
      methods was 37.3% (P < 0.001). Two-paired comparisons with the VIDAS SLM method
      were also performed. McNemar values were systematically highly significant (P <
      0.001). The proportion of agreement was significantly inferior (P < 0.05) for the
      comparison of VIDAS ICS and VIDAS SLM (68.7%) compared with the two other paired
      comparisons (average percentage, 81.5%). The conclusion reached by this trial is
      that VIDAS SLM significantly improves the recovery of Salmonella in naturally
      contaminated fecal specimens. For the paired-comparisons, NMKL 71 and SP-VG-M002
      were comparable in terms of efficiency, whereas the VIDAS ICS protocol, as
      established by the manufacturer for food samples only, seemed less efficient than
      the other two.

PMID- 15508625
TI  - A multistate outbreak of Salmonella enterica serotype typhimurium infection
      linked to raw milk consumption--Ohio, 2003.
AB  - In December 2002, the Ohio Department of Health was notified of two children with
      Salmonella infection. Both had a history of drinking raw milk from a combination
      dairy-restaurant-petting zoo (dairy). The dairy was the only establishment in
      Ohio licensed to sell raw milk and reported 1.35 million visitors annually. We
      investigated to determine the extent of the outbreak and identify illness risk
      factors. A case patient was any person with pulsed-field gel electrophoresis
      matched Salmonella enterica serotype Typhimurium from 30 November 2002 to 18
      February 2003. Sixty-two met the confirmed case definition. Forty dairy case
      patient patrons were included in a case-control study; 56 controls were their
      well meal companions. Consumption of raw milk was found to be associated with
      illness (odds ratio, 45.1; 95% confidence interval, 8.8 to 311.9). The dairy
      discontinued selling raw milk. Because 27 other states still allow the sale of
      raw milk, awareness of the hazards of its consumption should be raised and
      relevant regulations carefully reviewed.

PMID- 15508626
TI  - Detection of seven virulence and toxin genes of Campylobacter jejuni isolates
      from Danish turkeys by PCR and cytolethal distending toxin production of the
      isolates.
AB  - A total of 117 Campylobacter jejuni isolates from Danish turkeys were tested for
      the presence of seven virulence and toxin genes by PCR. One hundred seventeen
      (100%) isolates were positive for flaA, cadF, and ceuE gene primers. One hundred
      three (88%) isolates were positive for cdt gene cluster PCR detection (cdt gene
      cluster-PCR), whereas 101 (86.3%), 102 (87.2%), and 110 (94%) isolates were
      positive for cdtA-, cdtB-, and cdtC-PCR, respectively. Only 39 (33.3%) isolates
      were positive for virB11. Of 117 isolates, 114 (97.4%) produced cytolethal
      distending toxin (CDT) in Vero cell assays, 105 (89.7%) in Colon 205 assays, and
      109 (93.2%) in chicken embryo cell assays. The CDT titers were determined in Vero
      cell assays. Of 117 isolates, 50 (42.7%) produced a CDT titer of 1:100, 29
      (24.8%) of 1:50, and 27 (23%) of 1:5 to 1:10; 8 (6.8%) produced a CDT titer at
      undiluted supernatants and 3 (2.6%) produced no toxin. Twenty-nine C. jejuni
      isolates that were PCR negative for one or more individual cdt toxin genes also
      produced low or no CDT toxin. The high prevalence of the seven virulence and
      toxin genes demonstrates that these putative pathogenic determinants are
      widespread among Campylobacter isolates from turkeys and calls for further
      investigation for the elimination of Campylobacter infection in industrial turkey
      production and in industrial food chains.

PMID- 15508627
TI  - Effect of intertidal exposure on Vibrio parahaemolyticus levels in Pacific
      Northwest oysters.
AB  - Interest in Vibrio parahaemolyticus (Vp) increased in the United States following
      Vp-associated gastroenteritis outbreaks in 1997 and 1998 involving the West Coast
      and other areas. The present study evaluated multiple aspects of Vp ecology in
      the Pacific Northwest with three objectives: (i) to determine the effect of low
      tide exposure on Vp levels in oysters, (ii) to determine the relationship between
      total and pathogenic Vp, and (iii) to examine sediments and aquatic fauna as
      reservoirs for pathogenic Vp. Samples were collected from intertidal reefs along
      Hood Canal, Wash., in August 2001. Fecal matter from marine mammals and aquatic
      birds as well as intestinal contents from bottom-dwelling fish were tested. Total
      and pathogenic Vp levels in all the samples were enumerated with colony
      hybridization procedures using DNA probes that targeted the thermolabile direct
      hemolysin (tlh) and thermostable direct hemolysin (tdh) genes, respectively. The
      mean Vp densities in oysters were four to eight times greater at maximum exposure
      than at the corresponding first exposure. While tdh-positive Vp counts were
      generally < or = 10 CFU/g at first exposure, counts as high as 160 CFU/g were
      found at maximum exposure. Vp concentrations in sediments were not significantly
      different from those in oysters at maximum exposure. Pathogenic (tdh positive) Vp
      was detected in 9 of 42 (21%) oyster samples at maximum exposure, in 5 of 19
      (26%) sediment samples, but in 0 of 9 excreta samples. These results demonstrate
      that summer conditions permit the multiplication of Vp in oysters exposed by a
      receding tide.

PMID- 15508628
TI  - Response of heat-shocked Vibrio parahaemolyticus to subsequent physical and
      chemical stresses.
AB  - Vibrio parahaemolyticus foodborne strains 405, 556, and 690 and a V.
      parahaemolyticus chopping board isolate were heat shocked at 42 degrees C for 15,
      30, or 45 min. Heat shock, regardless of heating periods tested, caused an
      increased demand for NaCl during recovery from heat injury. Further study with
      strain 690 and the chopping board isolate also revealed that heat shock generally
      increased the survival of the test organism during subsequent exposure to 47
      degrees C, 20 ppm H202, and 8% ethanol and reduced the tolerance of the test
      organism to low temperatures (5 and -18 degrees C). The extent of the heat shock
      response of V. parahaemolyticus varied with strain and the duration of treatment.
      Furthermore, heat shock treatments in the present study caused the leakage of
      nucleic acids from V. parahaemolyticus cells. This effect was most pronounced
      with cells heat shocked at 42 degrees C for 45 min.

PMID- 15508629
TI  - Occurrence of Listeria monocytogenes in green table olives.
AB  - Microbiological safety of green table olives from different cultivars, prepared
      by both the Spanish-style and biological methods and fermented with starter
      cultures of lactic acid bacteria (Lactobacillus plantarum, Lactobacillus casei,
      and Lactobacillus pentosus), was investigated. The fermentation process was
      monitored by measuring pH values, titratable acidities, and growth of lactic acid
      bacteria over time. During fermentation, lactic acid bacteria and yeasts were
      major microbial populations. Microbiological safety was evaluated by analysis for
      Listeria monocytogenes with the use of an enrichment method during storage (from
      55 days to 18 months). Results demonstrated that L. monocytogenes can survive and
      grow in green table olives. L. monocytogenes was found in one of the commercial
      (thermally treated) samples analyzed and in all samples older than 2 months,
      irrespective of olive cultivar, lactic acid bacteria starter used, pH and
      titratable acidity of brine samples, or treatment applied.

PMID- 15508630
TI  - Modeling the growth boundary of Listeria monocytogenes in ready-to-eat cooked
      meat products as a function of the product salt, moisture, potassium lactate, and
      sodium diacetate concentrations.
AB  - A central composite response surface design was used to determine the time to
      growth of Listeria monocytogenes as a function of four continuous variables:
      added sodium chloride (0.8 to 3.6%), sodium diacetate (0 to 0.2%), potassium
      lactate syrup (60% [wt/wt]; 0.25 to 9.25%), and finished-product moisture (45.5
      to 83.5%) in ready-to-eat cured meat products. The design was repeated for ready
      to-eat uncured meat products giving a fifth categorical variable for cure status.
      Products were stored at 4 degrees C. The results were modeled using a generalized
      regression approach. All five main effects, six two-factor interactions, and two
      quadratic terms were statistically significant. The model was used to show the
      boundary between growth and no-growth conditions at 4 degrees C using contour
      plots of time to growth. It was validated using independent challenge studies of
      cured and uncured products. Generally, the model predicted well, particularly for
      cured products, where it will be useful for establishing conditions that prevent
      the growth of L. monocytogenes. For uncured products, there was good agreement
      overall between predicted and observed times to growth, but the model is less
      thoroughly validated than for cured products. The model should initially only be
      used for screening of formulations likely to prevent growth of Listeria
      monocytogenes in uncured products, with recommendations subject to confirmation
      by challenge studies.

PMID- 15508631
TI  - Survival, growth, and thermal resistance of Listeria monocytogenes in products
      containing peanut and chocolate.
AB  - Outbreaks of listeriosis associated with the consumption of ready-to-eat foods
      have raised interest in determining growth, survival, and inactivation
      characteristics of Listeria monocytogenes in a wide range of products. A study
      was undertaken to determine the thermal tolerance of L. monocytogenes in a peanut
      based beverage (3.1% fat), whole-fat (3.5%) milk, wholefat (4.0%) and reduced-fat
      (1.0%) chocolate milk, a chocolate-peanut spread (39% fat), and peanut butter
      (53% fat). The D60 degrees C value (decimal reduction time at 60 degrees C) in
      peanut beverage (3.2 min) was not significantly different (P > 0.05) than the D60
      degrees C value in whole-fat milk (3.3 min) or whole-fat chocolate milk (4.5 min)
      but significantly lower (P < or = 0.05) than the D60 degrees C value in reduced
      fat chocolate milk (5.9 min). The pathogen was significantly more resistant to
      heat when enmeshed in chocolate-peanut spread (water activity [aw] of 0.46; D60
      degrees C = 37.5 min) and peanut butter (aw of 0.32; D60 degrees C = 26.0 min)
      than in liquid products. At 10 degrees C, the pathogen grew most rapidly in whole
      fat chocolate milk and slowest in peanut beverage. At 22 degrees C, populations
      increased significantly within 12 and 16 h in whole-fat milk and reduced-fat
      chocolate milk, respectively, and within 8 h in whole-fat chocolate milk and
      peanut beverage. Initial populations (3.37 to 4.42 log CFU/g) of L. monocytogenes
      in chocolate-peanut spread and peanut butter adjusted to an aw of 0.33 and 0.65
      declined, but the pathogen was not eliminated during a 24-week period at 20
      degrees C. Survival was enhanced at reduced aw. Results indicate that a
      pasteurization process similar to that used for full-fat milk would be adequate
      to ensure the destruction of L. monocytogenes in peanut beverage. The pathogen
      survives for at least 24 weeks in chocolate-peanut spread and peanut butter at an
      aw range that encompasses that found in these products.

PMID- 15508632
TI  - Improved quantitative recovery of Listeria monocytogenes from stainless steel
      surfaces using a one-ply composite tissue.
AB  - Four sampling devices, a sterile environmental sponge (ES), a sterile cotton
      tipped swab (CS), a sterile calcium alginate fiber-tipped swab (CAS), and a one
      ply composite tissue (CT), were evaluated for quantitative recovery of Listeria
      monocytogenes from a food-grade stainless steel surface. Sterile 304-grade
      stainless steel plates (6 by 6 cm) were inoculated with approximately 106 CFU/cm2
      L. monocytogenes strain Scott A and dried for 1 h. The ES and CT sampling devices
      were rehydrated in phosphate buffer solution. After plate swabbing, ES and CT
      were placed in 40 ml of phosphate buffer solution, stomached for 1 min and hand
      massaged for 30 s. Each CS and CAS device was rehydrated in 0.1% peptone before
      swabbing. After swabbing, CS and CAS were vortexed in 0.1% peptone for 1 min.
      Samples were spiral plated on modified Oxford agar with modified Oxford agar
      Rodac Contact plates used to recover any remaining cells from the stainless steel
      surface. Potential inhibition from CT was examined in both phosphate buffer
      solution and in a modified disc-diffusion assay. Recovery was 2.70, 1.34, and
      0.62 log greater using CT compared with ES, CS, and CAS, respectively, with these
      differences statistically significant (P < 0.001) for ES and CT and for CAS, CS,
      and CT (P < 0.05). Rodac plates were typically overgrown following ES, positive
      after CS and CAS, and negative after CT sampling. CT was noninhibitory in both
      phosphate buffer solution and the modified disc-diffusion assay. Using scanning
      electron microscopy, Listeria cells were observed on stainless steel plates
      sampled with each sampling device except CT. The CT device, which is inexpensive
      and easy to use, represents a major improvement over other methods in quantifying
      L. monocytogenes on stainless steel surfaces and is likely applicable to
      enrichment of environmental samples.

PMID- 15508633
TI  - Efficacy of two cleaning and sanitizing combinations on Listeria monocytogenes
      biofilms formed at low temperature on a variety of materials in the presence of
      ready-to-eat meat residue.
AB  - Biofilms in the food-processing industry are a serious concern due to the
      potential for contamination of food products, which may lead to decreased food
      quality and safety. The effect of two detergent and sanitizer combinations on the
      inactivation of Listeria monocytogenes biofilms was studied. Combination A uses a
      chlorinated-alkaline, low-phosphate detergent, and dual peracid sanitizer.
      Combination B uses a solvated-alkaline environmental sanitation product and
      hypochlorite sanitizer. The survival of bacterial biofilms placed at 4 and 10
      degrees C and held for up to 5 days was also addressed. To simulate conditions
      found in a ready-to-eat meat-processing environment, biofilms were developed in
      low-nutrient conditions at 10 degrees C (with and without meat and fat residue)
      on a variety of materials found in a plant setting. Included were two types of
      stainless steel, three materials for conveyor use, two rubber products, a wall,
      and floor material. Biofilms developed on all surfaces tested; numbers at day 2
      ranged from 3.2 log on silicone rubber to 4.47 log CFU/cm2 on Delrin, an acetal
      copolymer. Biofilm survival during storage was higher at 4 degrees C (36.3 to
      1,621%) than 10 degrees C (4.5 to 83.2%). Small amounts of meat extract,
      frankfurters, or pork fat reduced biofilm formation initially; with time, the
      biofilm cell number and survival percentage increased. Cleaning efficacy was
      surface dependent and decreased with residue-soiled surfaces; biofilms developed
      on the brick and conveyor material were most resistant. Both detergents
      significantly (P < 0.05) removed or inactivated biofilm bacteria. The sanitizers
      further reduced biofilm numbers; however, the reduction was not significant in
      most cases for the dual peracid. Using a benchmark efficacy of >3-log reduction,
      combination A was only effective on 50.0% of the samples, Combination B, at
      86.1%, was more effective.

PMID- 15508634
TI  - Effect of commonly used enhancement solutions on the viability of Toxoplasma
      gondii tissue cysts in pork loin.
AB  - Retail meat cuts of pork are frequently enhanced with salt solutions to improve
      flavor and texture and to extend shelf life through reductions in microbial
      contamination. A study of the effect of commonly used meat enhancement solutions
      on the viability of Toxoplasma gondii tissue cysts was performed using tissues
      from experimentally infected mice and pigs. Brains of T. gondii-infected mice
      were injected to 110% of the original weight of the brain with solutions
      containing sodium chloride (1 and 2%), sodium diacetate (0.1 and 0.2%), sodium
      tripolyphosphate (0.25 and 0.5%), potassium lactate (1.4 and 1.96%), or sodium
      lactate (1.4, 1.5, and 2.0%) alone or in combination and stored at 4 degrees C
      for 7 days before feeding to T. gondii-seronegative cats. Loins were collected
      from pigs experimentally infected with T. gondii and injected as above and stored
      for 7, 28, or 45 days at 4 degrees C before feeding to T. gondii-seronegative
      cats. Cat feces were examined for 14 days to assess oocyst shedding. The present
      study demonstrated that injection of mouse brains or pork loins with solutions
      containing 2% sodium chloride or > or =1.4% potassium or sodium lactate, alone or
      in combination with other components, prevented transmission of T. gondii to
      cats.

PMID- 15508635
TI  - Characterization of molds from dry-cured meat products and their metabolites by
      micellar electrokinetic capillary electrophoresis and random amplified
      polymorphic DNA PCR.
AB  - Molds are common contaminants of dry-cured meat products in which mycotoxins
      could be synthesized if stored under favorable conditions. Thus, efficient and
      accurate characterization of the toxigenic molds from dry-cured meat products is
      necessary. A micellar electrokinetic capillary chromatography (MECC) method was
      tested to analyze secondary metabolites produced by 20 mold strains commonly
      found in dry-cured meat products. In addition, their random amplified polymorphic
      DNA (RAPD) genotypes were determined by using a PCR method. Although peak
      profiles of the secondary metabolites differed among mold strains of different
      species, they were similar in the same species. MECC analysis showed that 10 of
      the 20 molds tested produced mycotoxins, including patulin, penicillic acid,
      cyclopiazonic acid, mycophenolic acid, aflatoxin B1, sterigmatocystin, and
      griseofulvin. The RAPD analysis yielded a different pattern for each of the mold
      species tested. However, strains of the same species showed similar RAPD
      profiles. A high correlation between RAPD analysis and MECC was observed, since
      strains of the same species that showed similar RAPD patterns had similar
      profiles of secondary metabolites. RAPD patterns with primer GO2 and MECC
      profiles, either singly or combined, could be of great interest to distinguish
      toxigenic from nontoxigenic molds in dry-cured meat products.

PMID- 15508636
TI  - Influence of fruit variety, harvest technique, quality sorting, and storage on
      the native microflora of unpasteurized apple cider.
AB  - Apple variety, harvest, quality sorting, and storage practices were assessed to
      determine their impact on the microflora of unpasteurized cider. Seven apple
      varieties were harvested from the tree or the ground. The apples were used fresh
      or were stored at 0 to 4 degrees C for < or = 5 months and were pressed with or
      without quality selection. Cider yield, pH, Brix value, and titratable acidity
      were measured. Apples, postpressing apple pomace, and cider samples were analyzed
      for aerobic bacteria, yeasts, and molds. Aerobic bacterial plate counts (APCs) of
      ciders from fresh ground-picked apples (4.89 log CFU/ml) were higher than those
      of ciders made from fresh, tree-picked apples (3.45 log CFU/ml). Quality sorting
      further reduced the average APC to 2.88 log CFU/ml. Differences among all three
      treatment groups were significant (P < 0.0001). Apple and pomace microbial
      concentrations revealed harvest and postharvest treatment-dependent differences
      similar to those found in cider. There were significant differences in APC among
      apple varieties (P = 0.0001). Lower counts were associated with varieties
      exhibiting higher Brix values and higher titratable acidity. Differences in APC
      for stored and fresh apples used for cider production were not significant (P >
      0.05). Yeast and mold counts revealed relationships similar to those for APCs.
      The relationship between initial microbial load found on incoming fruit and final
      cider microbial population was curvilinear, with the weakest correlations for the
      lowest apple microflora concentrations. The lack of linearity suggests that
      processing equipment contributed to cider contamination. Tree-picked quality
      fruit should be used for unpasteurized cider production, and careful
      manufacturing practices at cider plants can impact both safety and quality of the
      final product.

PMID- 15508637
TI  - Decreased dosage of acidified sodium chlorite reduces microbial contamination and
      maintains organoleptic qualities of ground beef products.
AB  - Acidified sodium chlorite (ASC) spray was evaluated at decreased dosages and
      application rates to determine its efficacy for reducing bacterial contamination
      on boneless beef trimmings used for production of raw ground beef products while
      maintaining desirable consumer qualities in the finished ground beef products.
      Two different applications of ASC (600 ppm applied at a rate of 1.3 oz/lb and 300
      ppm applied at a rate of 1 oz/lb) were used to treat boneless beef trimmings
      before grinding. The effect of ASC treatment on 50/50 lean beef trimmings was
      greater than on 90/10 trimmings. ASC at 600 ppm reduced both the aerobic plate
      counts (APC) and Enterobacteriaceae counts (EBC) by 2.3 log CFU/g on 50/50
      trimmings, whereas treatment with 300 ppm ASC reduced APC and EBC of 50/50
      trimmings by 1.1 and 0.7 log CFU/g, respectively. Ground beef formulations of
      90/10 and 73/27 were produced from the treated boneless beef trim and packaged in
      chubs and in modified atmosphere packaging. The efficacy of ASC spray treatment
      to inhibit APC and EBC over the shelf life of each ground beef product was
      monitored. The APC and EBC in ground beef chubs were reduced by 1.0 to 1.5 log
      CFU/g until day 20. The APC and EBC for products in modified atmosphere packaging
      were reduced 1.5 to 3.0 log CFU/g throughout their shelf life. Both decreased
      dosages of ASC were equally effective on 90/10 lean ground beef, but the 300 ppm
      ASC treatment was slightly better at reducing the EBC of 73/27 ground beef. The
      organoleptic qualities (color, odor, and taste) of the ground beef products
      treated with 300 ppm ASC were found to be superior to those treated with 600 ppm
      ASC. Our results indicated that decreased dosages of ASC reduce contamination and
      lengthen the shelf life of ground beef. Furthermore, the 300 ppm ASC treatment
      reduced bacterial counts while maintaining desirable organoleptic ground beef
      qualities.

PMID- 15508638
TI  - Chemical analysis and sensory evaluation of mahi-mahi (Cryphaena hippurus) during
      chilled storage.
AB  - Biogenic amines, total volatile base-nitrogen (TVB-N), and sensory evaluation are
      some of the indicators used for fish quality determination. Our objective was to
      evaluate the relationship among histamine, cadaverine, putrescine, TVB-N, and
      sensory evaluation as quality assessment tools. Two groups of six mahi-mahi
      fillets were refrigerated at 7 degrees C and sampled on days 0, 2, 4, 6, 8, and
      10. On day 3, histamine, cadaverine, and putrescine levels reached 5, 3, and 0.5
      mg/100 g, respectively, whereas TVB-N reached 30 mg/100 g. Sensory scores were 6
      to 6.5 (10 very fresh and 1 very spoiled) for odor, appearance, texture, and
      color. Correlations were 0.78 and 0.72 between histamine and cadaverine and
      histamine and putrescine, 0.74 and 0.80 between TVB-N and cadaverine and TVB-N
      and putrescine, and 0.75 and 0.78 between odor and putrescine and odor and
      cadaverine. AromaMaps showed distinct trends for deteriorating mahi-mahi
      (Coryphaena hippurus) quality.

PMID- 15508639
TI  - Irradiation to kill Escherichia coli O157:H7 and Salmonella on ready-to-eat
      radish and mung bean sprouts.
AB  - A study was carried out to evaluate the effectiveness of ionizing radiation in
      eliminating Escherichia coli O157:H7 and Salmonella on commercial ready-to-eat
      radish and mung bean sprouts and to assess the chemical and physical quality of
      these sprouts. The use of ionizing radiation was investigated as a means of
      reducing or totally inactivating these pathogens, if present, on the sprouts.
      Treatment of mung bean and radish sprouts with a dose of 1.5 and 2.0 kGy,
      respectively, significantly reduced E. coli O157:H7 and Salmonella to
      nondetectable limits. The total vitamin C content was gradually reduced with the
      increase in irradiation dose (P < 0.0001). However, the effect of storage
      interval on the loss of vitamin C was nonsignificant for radish sprouts and
      significant for mung bean sprouts (P < 0.04). The color, firmness, and overall
      visual quality of the tested sprouts were acceptable when effective doses were
      applied to both radish and mung bean sprouts. Therefore, ionizing radiation could
      be useful in reducing the population of pathogens on sprouts and yet retain
      acceptable quality parameters.

PMID- 15508640
TI  - Influence of a nonfavorable environment, egg white, on resistance to heat and
      disinfectant, adhesion, and virulence of Salmonella enteritidis.
AB  - Although liquid egg white may be subjected to limited heat treatment when it is
      used in the fabrication of various foodstuffs, pathogenic bacteria such
      Salmonella Enteritidis could persist in this environment. Liquid egg white is not
      a favorable medium for Salmonella growth because of its alkaline pH and iron
      deficiency and the presence of ovotransferrin. Microorganisms adapted to a
      nonfavorable environment are often more resistant to stresses than are their
      laboratory-cultured counterparts. The objective of this study was to determine
      whether Salmonella exposed to an environment mimicking egg white conditions
      exhibited modified behavior that could have an impact on food safety. A medium
      resembling egg white (filtrate of egg white with added ovotransferrin) was used
      as an adaptation treatment to mimic the stress imparted by the egg white
      environment. There were no changes in resistance to heat and disinfection, in
      stainless steel adhesion, or in the virulence of Salmonella Enteritidis
      cultivated in the egg white medium. Egg white conditions do not appear to make
      Salmonella more virulent or more difficult to inactivate.

PMID- 15508641
TI  - Prevalence of Escherichia coli O157 in cattle and swine in central Mexico.
AB  - Escherichia coli O157:H7 is a foodborne pathogenic bacterium that can reside
      undetected in the gastrointestinal tract of cattle because colonization by this
      bacterium is asymptomatic. Recent research has indicated that swine can carry and
      transmit this pathogen as well. The development of more advanced and sensitive
      detection techniques has improved the limit of detection and increased
      sensitivity for this important pathogen. This study was undertaken to determine
      the prevalence of E. coli O157 in cattle and swine in Mexico with the more
      sensitive detection technique of immunomagnetic bead separation. Samples (n = 60
      per farm) were taken from four cattle and four swine farms (n = 240 cattle
      samples, n = 240 swine samples) located throughout central Mexico in October
      2001. The prevalence of E. coli O157 was found to be only 1.25% on cattle farms
      and 2.1% on swine farms. The prevalence in cattle in this study is lower than
      that reported in the United States and could be related to the lower reported
      prevalence of E. coli O157 in humans in Mexico. However, further research is
      needed to verify prevalence throughout other regions of Mexico, as well as
      prevalence during other seasons of the year.

PMID- 15508642
TI  - Survival of Salmonella Montevideo on tomato leaves and mature green tomatoes.
AB  - Survival of Salmonella Montevideo on tomato leaf and mature green tomatoes was
      examined. When spiked on the surfaces of excised leaves from greenhouse tomato
      plants, Salmonella Montevideo survived poorly if the leaves were allowed to dry.
      After spot inoculation of 6.6 log CFU per leaflet and incubation for 48 h at 60%
      relative humidity, the leaflets were dried, and surviving Salmonella were reduced
      2.8 to 3.7 log CFU per leaflet. However, when leaves spiked with Salmonella were
      supported on hydroponic nutrient medium and incubated at 100% relative humidity,
      there was no significant reduction of surviving bacteria for at least 6 days.
      Exposure of mature green tomatoes to ethylene (100 ppm at 100% relative humidity
      and 20 degrees C for 6 days) did not significantly affect the survival of
      Salmonella on their surfaces. The significance of these data to pre- and
      postharvest safety of tomato is discussed.

PMID- 15508643
TI  - Salmonella genotype diversity in nonlactating and lactating dairy cows.
AB  - Dairy cows may serve as asymptomatic carriers of Salmonella. The potential for
      herd carrier status increases with herd size, and Salmonella shedding may be
      triggered by stresses placed on the animals. The scope of the current study is to
      determine the effects lactation may have on Salmonella genotypic diversity among
      detected serotypes. Fecal samples were collected on two sampling dates from 60
      nonlactating and 60 lactating Holstein cows. No serotype was predominant over the
      two collection dates, although Salmonella Albany, Salmonella Anatum, Salmonella
      Newport, and Salmonella Senftenberg were detected in relatively high numbers.
      Twenty-three genotypes were detected on the first date and 27 on the second date.
      The greatest genotypic diversity was seen among Salmonella Newport and Salmonella
      Senftenberg, with five and nine genotypes, respectively. The presence of multiple
      serotypes and genotypes in the herd suggests multiple contamination sources.
      However, there was no conclusive effect of lactation status of the cows on
      Salmonella genotypic shedding.

PMID- 15508644
TI  - Market survey of Vibrio spp. and other microrganisms in Italian shellfish.
AB  - A survey was conducted of Vibrio spp., Escherichia coli, fecal coliforms, and
      Salmonella in 644 molluscan shellfish samples marketed in the Apulia region of
      southern Italy. Vibrios were found in 278 samples (43%), and levels of E. coli
      and fecal coliforms were above the Italian legal limit in 27 and 34 samples (4
      and 5%), respectively. Salmonella was not detected in any of the samples. Because
      the majority of the vibrio isolates were found in samples that were compliant
      with Italian regulations, there appears to be no relationship between the
      presence of microorganisms of fecal origin and the presence of vibrios
      potentially harmful to human health.

PMID- 15508645
TI  - Effects of postchill application of acidified sodium chlorite to control
      Campylobacter spp. and Escherichia coli on commercial broiler carcasses.
AB  - Experiments were performed to assess the reduction of Campylobacter spp. and
      Escherichia coli in commercial broiler carcasses by postchill dip applications of
      acidified sodium chlorite. Carcass rinses were collected before the inside
      outside-bird washer (IOBW), post-IOBW, postchill, and after the postchill
      application of acidified sodium chlorite. Prevalence and counts of Campylobacter
      spp. and E. coli were determined. The mean values for Campylobacter spp. and E.
      coli counts differed significantly at sampling sites. The IOBW reduced the
      bacterial counts significantly in only one experiment. The chiller reduced
      Campylobacter counts significantly in both experiments but failed to
      significantly reduce the counts of E. coli in one experiment. No major reduction
      in the prevalence after enrichment for Campylobacter spp. was detected post-IOBW
      or postchill. However, a significant reduction in Campylobacter spp. and in E.
      coli counts and Campylobacter spp. prevalence was seen after the postchill
      application of acidified sodium chlorite. These results demonstrate that the
      antimicrobial effect of acidified sodium chlorite applied postchill may be used
      to significantly reduce Campylobacter spp. and E. coli in commercial broiler
      carcasses. Postchill systems may eventually be used in different applications,
      such as mist, spray, or bath, which could be applied closer to the final stages
      in processing.

PMID- 15508646
TI  - Resistance to gentamicin and vancomycin in enterococcal strains isolated from
      retail broiler chickens in Japan.
AB  - A total of 137 Enterococcus strains isolated from chicken meat were subjected to
      antimicrobial susceptibility tests. Strains with the vanCl gene were isolated
      from seven of nine samples of chicken meat processed in Japan and from all
      chickens from China and Brazil between July 2001 and April 2002. The pulsed-field
      gel electrophoresis (PFGE) patterns of the isolates were distinguishable from
      each other, suggesting that VanCl-type vancomycin-resistant Enterococcus is
      preferentially colonized in broiler chickens in these countries. The incidence of
      high-level gentamicin resistant (HLGR) enterococci that harbored the aac(6')-le
      aph(2")-la or aph(2')-Id gene varied among the countries from which the chickens
      originated (Japan, 2 of 65; China, 11 of 43; Brazil, 6 of 29). Moreover, the PFGE
      patterns of the HLGR strains were distinguishable from each other, except for two
      strains obtained from chickens from Brazil. The results suggest that HLGR
      Enterococcus is highly prevalent in broiler chickens.

PMID- 15508647
TI  - Control of Listeria monocytogenes with combined antimicrobials on beef franks
      stored at 4 degrees C.
AB  - Contamination of ready-to-eat meat products such as beef franks with Listeria
      monocytogenes has become a major concern for the meat processing industry and an
      important food safety issue. The objective of this study was to determine the
      effectiveness of combinations of antimicrobials as aqueous dipping solutions to
      control L. monocytogenes on vacuum-packaged beef franks stored at 4 degrees C for
      3 weeks. Commercial beef franks were dipped for 5 min in three antimicrobial
      solutions: pediocin (6,000 AU), 3% sodium diacetate and 6% sodium lactate
      combined, and a combination of the three antimicrobials. Samples were then
      inoculated with 10(7) CFU/g of either four L. monocytogenes strains individually
      or a cocktail of the four strains, vacuum packaged, and stored at 4 degrees C for
      3 weeks. Sampling was carried out at day 0 and after 2 and 3 weeks of storage.
      Individual strains, as well as the cocktail, exhibited different responses to the
      antimicrobial treatments. After 2 and 3 weeks of storage at 4 degrees C, pediocin
      treated beef franks showed a less than 1-log reduction for all bacterial strains.
      Samples treated with the sodium diacetate-sodium lactate combination showed about
      a 1-log reduction after 2 weeks of storage for all strains and between a 1- and 2
      log reduction after 3 weeks of storage, depending on the bacterial strain. When
      the three antimicrobials were combined, reductions ranged between 1 and 1.5 log
      units and 1.5 to 2.5 log units after 2 and 3 weeks of storage, respectively, at 4
      degrees C. These results indicate that the use of combined antimicrobial
      solutions for dipping treatments is more effective at inhibiting L. monocytogenes
      than treatments using antimicrobials such as pediocin separately.

PMID- 15508648
TI  - Development of a PCR test to differentiate between Staphylococcus aureus and
      Staphylococcus intermedius.
AB  - The presence of Staphylococcus intermedius in food remains unclear because
      routine laboratory analysis does not discriminate between S. intermedius and
      Staphylococcus aureus, a major cause of food poisoning. Both species share many
      phenotypic characteristics, including coagulase and thermonuclease production. In
      both species, some strains can produce enterotoxin and therefore can be the cause
      of food poisoning outbreaks. Although the ID32 Staph System (bioMerieux, SA,
      Marcy l'Etoile, France), based on a miniaturized phenotypic characterization,
      gives satisfactory results for discriminating between these two species, some
      rapid molecular PCR-based methods have been developed to identify S. aureus
      specifically, but they do not identify S. intermedius. Here, we developed a
      rapid, accurate, and discriminative multiplex PCR method that targets species
      specific sequences in the nuc gene, which encodes thermonuclease in the two
      species. The test includes an internal positive control that targets a highly
      conserved region of 16S ribosomal RNA gene (rDNA). A total of 116 strains were
      used to validate our test. The test gave no signal on the following
      Staphylococcus species: S. epidermidis, S. chromogenes, S. hyicus, S. warneri, S.
      xylosus, S. lentus, and S. sciuri. It allowed a 100% successful discrimination
      between S. aureus (44 strains tested) and S. intermedius (57 strains) isolated
      from different origins.

PMID- 15508649
TI  - Population dynamics of the constitutive biota of French dry sausages in a pilot
      scale ripening chamber.
AB  - The population dynamic of constitutive biota on 84 samples belonging to two
      different types of French fermented dry sausages during the ripening process in a
      pilot-scale ripening chamber was investigated. Samples were analyzed in three
      steps of their production: fresh product, first drying stage, and finished
      product. In addition, 180 strains of lactic acid bacteria were identified using a
      miniaturized biochemical procedure of characterization. In general, the number of
      lactic acid bacteria that evolved during the ripening process of French dry
      sausages increased during the first days of the process after which the number of
      these organisms remained constant at approximately 8 log CFU/g. Lactobacillus
      sakei and Pediococcus pentosaceus, bacteria added as starter, were the dominant
      species. Pediococcus urinaeequi, Pediococcus acidilactici, and particularly
      Lactobacillus curvatus were also present. Finally, we have to take into account
      that the controlled conditions of the pilot plant generally contribute to the
      homogenization of the behavior of the starter biota.

PMID- 15508650
TI  - Comparison of PCR prescreening to two cultivation procedures with PCR
      confirmation for detection of Mycobacterium avium subsp. paratuberculosis in U.S.
      Department of Agriculture fecal check test samples.
AB  - Mycobacterium avium subsp. paratuberculosis (MAP) is the etiologic agent in
      Johne's disease in cattle and causes diarrhea, decreased milk production,
      emaciation, and frequently death. The ability to detect MAP rapidly and
      accurately is an integral part of herd management. However, detection of this
      bacterium is complicated due to its slow division time and its ability to enter
      dormancy. Culture methods are considered the "gold standard," but they have their
      limitations. Many enzyme-linked immunosorbent assay methods and conventional PCR
      methods have been used as diagnostic tools. The present study compares the
      results of a PCR prescreen to two culture methods of detection paired with
      confirmatory PCR to determine the most accurate, rapid, and sensitive method
      using U.S. Department of Agriculture (USDA) fecal check samples. This study
      involving two laboratories (Marshfield Clinic Laboratories, using solid culture
      medium [Herrold's egg yolk agar], and TREK Diagnostic Systems Research and
      Development, using liquid culture medium [ESP Culture System II]) showed that the
      PCR prescreening method used in this study lacked specificity and sensitivity as
      a stand-alone test in fecal samples. However, the combination of liquid
      enrichment culture using the ESP II system, and PCR confirmation with the hspX
      primer set, was not only 100% sensitive and specific but also correlated with
      viable MAP and USDA culture results.

PMID- 15508651
TI  - Round-robin comparison of methods for the detection of human enteric viruses in
      lettuce.
AB  - Five methods that detect human enteric virus contamination in lettuce were
      compared. To mimic multiple contaminations as observed after sewage
      contamination, artificial contamination was with human calicivirus and poliovirus
      and animal calicivirus strains at different concentrations. Nucleic acid
      extractions were done at the same time in the same laboratory to reduce assay-to
      assay variability. Results showed that the two critical steps are the washing
      step and removal of inhibitors. The more reliable methods (sensitivity,
      simplicity, low cost) included an elution/concentration step and a commercial
      kit. Such development of sensitive methods for viral detection in foods other
      than shellfish is important to improve food safety.

PMID- 15508652
TI  - Physicochemical and microbiological profile of packed table olives.
AB  - The water activity of different commercial products of table olives as well as
      their physicochemical and microbiological profiles were studied. Average values
      of water activity were 0.976, 0.977, and 0.990 for green, directly brined, and
      ripe (by alkaline oxidation) olives, respectively. Mean values of pH were 3.69,
      3.92, and 6.52 while salt levels were 5.53, 4.98, and 2.55 for the same
      commercial products. In some of the commercial products of green and directly
      brined olives that were examined, a certain level of microorganisms was observed.
      Most of them were lactic acid bacteria and yeasts, the lactic acid bacteria being
      more abundant than the yeasts. Traditionally, this flora has not been considered
      harmful due to its resemblance to that found in natural and spontaneous
      fermentation. Spore-forming mesophilic aerobes, which can be considered
      contaminants from ingredient or product handling, were present in only some
      samples and were always at low levels. However, their detection does not cause
      any concern regarding safety because there is no reference showing that they can
      grow in any of the products studied given the physicochemical characteristics
      found.

PMID- 15508653
TI  - Evidence of organochlorine pesticide and polychlorinated biphenyl residues in
      Slovenian poultry tissues from 1997 to 1999.
AB  - The contamination of poultry tissues by total organochlorine (OC) pesticides and
      polychlorinated biphenyls (PCBs) in Slovenia was examined from a public health
      perspective. As part of systematic veterinary and sanitary monitoring of foods of
      animal origin from 1997 to 1999, 87 samples of fat tissue were examined for the
      presence of alpha-HCH, lindane, heptachlor, and total DDT (plus DDE and DDD) and
      88 samples of fat tissue were examined for the presence of total PCBs (sum of PCB
      congeners). The levels of poultry tissue contamination in six regions of Slovenia
      were determined. Levels of OC pesticides were below detection limits in 86.2% of
      analyses performed. Total PCB levels for most samples (59.1%) of poultry fat
      tissue were in the 0.002- to 0.02-mg/kg range. The level of contamination with OC
      pesticides and total PCBs in poultry fat tissue was not influenced by the type of
      poultry and was the highest in samples from industrial areas, which have been
      ecologically disturbed. All samples met Slovenian and European Union tolerances.

PMID- 15508654
TI  - Heavy metal contamination of European eel (Anguilla anguilla) and brown trout
      (Salmo trutta) caught in wild ecosystems in Spain.
AB  - In this study we analyzed the pattern of copper (Cu), cadmium (Cd), lead (Pb),
      and mercury (Hg) accumulation in liver (as a detoxifying organ) and muscle (as
      the most important tissue for human consumption) of brown trout (Salmo trutta)
      and European eel (Anguilla anguilla) caught in two wild Spanish rivers where both
      species are usually angled for human consumption. Cd, Pb, and Cu accumulated
      preferentially in the liver of both species. Hg accumulated both in the liver and
      muscle in brown trout, whereas it accumulated preferentially in muscle in
      European eel. Both high metal content and preferential accumulation of Hg in
      muscle suggest that European eel is more harmful than brown trout for human
      consumption.

PMID- 15508655
TI  - Effects of preparation methods on the microbiological safety of home-dried meat
      jerky.
AB  - Historically, drying meats to produce jerky was conisidered to be a safe
      preservation process and the convenience and flavor of jerky has made it a
      popular food product for home food preservers. Recent outbreaks of foodborne
      illness related to both home-dried and commercially manufactured jerky have
      raised concerns about the safety of the product. Some traditional home recipes
      and drying processes were shown to be inadequate to destroy Escherichia coli
      O157, Salmonella, Staphylococcus aureus, and Listeria monocytogenes in both whole
      muscle and ground-meat jerky. Several research studies have identified processes
      such as precooking meats before drying, usingacidic marinades, cooking meats
      after drying, or some combination of these treatments that can destroy pathogens
      of concern to produce microbiologically safe and palatable meat jerky at home.

PMID- 15508656
TI  - Fresh produce: a growing cause of outbreaks of foodborne illness in the United
      States, 1973 through 1997.
AB  - Fresh produce is an important part of a healthy diet. During the last three
      decades, the number of outbreaks caused by foodborne pathogens associated with
      fresh produce consumption reported to the Centers for Disease Control and
      Prevention has increased. To identify trends, we analyzed data for 1973 through
      1997 from the Foodborne Outbreak Surveillance System. We defined a produce
      associated outbreak as the occurrence of two or more cases of the same illness in
      which epidemiologic investigation implicated the same uncooked fruit, vegetable,
      salad, or juice. A total of 190 produce-associated outbreaks were reported,
      associated with 16,058 illnesses, 598 hospitalizations, and eight deaths. Produce
      associated outbreaks accounted for an increasing proportion of all reported
      foodborne outbreaks with a known food item, rising from 0.7% in the 1970s to 6%
      in the 1990s. Among produce-associated outbreaks, the food items most frequently
      implicated included salad, lettuce, juice, melon, sprouts, and berries. Among 103
      (54%) produce-associated outbreaks with a known pathogen, 62 (60%) were caused by
      bacterial pathogens, of which 30 (48%) were caused by Salmonella. During the
      study period, Cyclospora and Escherichia coli O157:H7 were newly recognized as
      causes of foodborne illness. Foodborne outbreaks associated with fresh produce in
      the United States have increased in absolute numbers and as a proportion of all
      reported foodborne outbreaks. Fruit and vegetables are major components of a
      healthy diet, but eating fresh uncooked produce is not risk free. Further efforts
      are needed to better understand the complex interactions between microbes and
      produce and the mechanisms by which contamination occurs from farm to table.

PMID- 15508657
TI  - Death by hyperventilation: a common and life-threatening problem during
      cardiopulmonary resuscitation.
AB  - CONTEXT: This translational research initiative focused on the physiology of
      cardiopulmonary resuscitation (CPR) initiated by a clinical observation of
      consistent hyperventilation by professional rescuers in out-of-hospital cardiac
      arrest. This observation generated scientific hypotheses that could only
      ethically be tested in the animal laboratory. OBJECTIVE: To examine the
      hypothesis that excessive ventilation rates during performance of CPR by
      overzealous but well-trained rescue personnel causes a significant decrease in
      coronary perfusion pressure and an increased likelihood of death. DESIGN AND
      SETTING: In the in vivo human aspect of the study, we set out to objectively and
      electronically record rate and duration of ventilation during performance of CPR
      by trained professional rescue personnel in a prospective clinical trial in
      intubated, adult patients with out-of-hospital cardiac arrest. In the in vivo
      animal aspect of the study, to simulate the clinically observed hyperventilation,
      nine pigs in cardiac arrest were ventilated in a random order with 12, 20, or 30
      breaths/min, and physiologic variables were assessed. Next, three groups of seven
      pigs in cardiac arrest were ventilated at 12 breaths/min with 100% oxygen, 30
      breaths/min with 100% oxygen, or 30 breaths/min with 5% CO2/95% oxygen, and
      survival was assessed. MAIN OUTCOME MEASURES: Ventilation rate and duration in
      humans; mean intratracheal pressure, coronary perfusion pressure, and survival
      rates in animals. RESULTS: In 13 consecutive adults (average age, 63 +/- 5.8 yrs)
      receiving CPR (seven men) the average ventilation rate was 30 +/- 3.2 breaths/min
      (range, 15 to 49 breaths/min) and the average duration of each breath was 1.0 +/-
      0.07 sec. The average percentage of time in which a positive pressure was
      recorded in the lungs was 47.3 +/- 4.3%. No patient survived. In animals treated
      with 12, 20, and 30 breaths/min, the mean intratracheal pressures and coronary
      perfusion pressures were 7.1 +/- 0.7, 11.6 +/- 0.7, 17.5 +/- 1.0 mm Hg/min (p <
      .0001) and 23.4 +/- 1.0, 19.5 +/- 1.8, 16.9 +/- 1.8 mm Hg (p = .03) with each of
      the different ventilation rates, respectively (p = comparison of 12 breaths/min
      vs. 30 breaths/min for mean intratracheal pressure and coronary perfusion
      pressure). Survival rates were six of seven, one of seven, and one of seven with
      12, 30, and 30 + CO2 breaths/min, respectively (p = .006). CONCLUSIONS: Despite
      seemingly adequate training, professional rescuers consistently hyperventilated
      patients during out-of-hospital CPR. Subsequent hemodynamic and survival studies
      in pigs demonstrated that excessive ventilation rates significantly decreased
      coronary perfusion pressures and survival rates, despite supplemental CO2 to
      prevent hypocapnia. This translational research initiative demonstrates an
      inversely proportional relationship between mean intratracheal pressure and
      coronary perfusion pressure during CPR. Additional education of CPR providers is
      urgently needed to reduce these newly identified and deadly consequences of
      hyperventilation during CPR. These findings also have significant implications
      for interpretation and design of resuscitation research, CPR guidelines,
      education, the development of biomedical devices, emergency medical services
      quality assurance, and clinical practice.

PMID- 15508658
TI  - Attenuated adult biphasic shocks for prolonged pediatric ventricular
      fibrillation: support for pediatric automated defibrillators.
AB  - OBJECTIVE: To evaluate published data regarding the treatment of prolonged
      pediatric defibrillation, with special emphasis on the use of attenuated adult
      biphasic shocks for pediatric defibrillation. DESIGN: Review relevant human and
      animal literature. RESULTS: Rhythm analysis algorithms from two manufacturers of
      automated external defibrillators can accurately distinguish shockable from
      nonshockable rhythms in children. Theoretical considerations and transthoracic
      impedance data from animals and children suggest that pediatric defibrillation
      doses should not necessarily vary in a simple weight-based manner. Two piglet
      studies have established that an attenuated adult biphasic dosage can be
      successfully used for 3.5- to 24-kg animals in ventricular fibrillation. One
      study established that the attenuated adult biphasic dosage was at least as safe
      and effective as the standard monophasic weight-based dosing. CONCLUSION: This
      review supports the American Heart Association's new guidelines for pediatric
      automated external defibrillator usage: "Automated external defibrillators may be
      used for children 1 to 8 yrs of age who have no signs of circulation. Ideally the
      device should deliver a pediatric dose. The arrhythmia detection system used in
      the device should demonstrate high specificity for pediatric shockable rhythms,
      i.e., it will not recommend delivery of a shock for nonshockable rhythms."

PMID- 15508659
TI  - Amplitude spectrum area: measuring the probability of successful defibrillation
      as applied to human data.
AB  - OBJECTIVE: The objective of our study was to examine the effectiveness of an
      electrocardiographic predictor, amplitude spectral area (AMSA), for the optimal
      timing of defibrillation shocks in human victims of cardiac arrest. Based on the
      spectral characteristics of ventricular fibrillation potentials, we examined the
      probability of successful conversion to an organized viable rhythm, including the
      return of spontaneous circulation. The incentive was to predict the likelihood of
      successful defibrillation and thereby improve outcomes by minimizing
      interruptions in chest compression and minimizing electrically induced myocardial
      injury due to repetitive high-current shocks. DESIGN: Observational study on
      human electrocardiographic recordings during cardiopulmonary resuscitation.
      SETTING: Medical research laboratory of a university-affiliated research and
      educational institute. PATIENTS: Victims of out-of-hospital cardiac arrest.
      INTERVENTIONS: Iteration of electrocardiographic records, representing lead 2
      equivalent recordings on 108 defibrillation attempts with an automated external
      defibrillator, of 46 victims of cardiac arrest due to ventricular fibrillation.
      MEASUREMENTS AND MAIN RESULTS: Three seconds of ventricular fibrillation,
      recorded immediately preceding delivery of a shock, were analyzed utilizing the
      AMSA algorithm. AMSA represents a numerical value based on the sum of the
      magnitude of the weighted frequency spectrum between 3 and 48 Hz. The greater the
      AMSA value, the greater was the probability of reversal of ventricular
      fibrillation. At an AMSA value of >13.0 mV-Hz, successful defibrillation yielded
      a sensitivity of .91 and a specificity of .94. CONCLUSION: AMSA predicts the
      success of electrical defibrillation with high specificity. AMSA therefore serves
      to minimize interruptions of precordial compression and the myocardial damage
      caused by delivery of repetitive and ineffective electrical shocks.

PMID- 15508660
TI  - Effects of intracerebroventricular application of brain-derived neurotrophic
      factor on cerebral recovery after cardiac arrest in rats.
AB  - SUBJECT: After transient global cerebral ischemia, selective vulnerable brain
      areas show delayed neurodegeneration with characteristics of apoptosis. Recent
      data demonstrate potent neuroprotective effects of the application of endogenous
      growth hormones such as brain-derived neurotrophic factor (BDNF) after focal
      cerebral ischemia. To assess possible effects of the intracerebroventricular
      application of BDNF on cerebral recovery after global cerebral ischemia due to
      cardiac arrest in rats, various selective vulnerable brain areas were
      investigated. INTERVENTIONS: Global cerebral ischemia was initiated by
      ventricular fibrillation in rats under general anesthesia. After 6 mins, the
      animals were resuscitated by external cardiac massage combined with
      defibrillation and divided into two groups (BDNF vs. placebo). BDNF or placebo (1
      microg/hr) was applied continuously during the complete reperfusion time using an
      implanted osmotic minipump. After 6 hrs, 24 hrs, 3 days, and 7 days (n = 6-7 per
      group), coronal brain sections were analyzed by terminal
      deoxynucleotidyltransferase-mediated d-uracil triphosphate-biotin nick end
      labeling (TUNEL) and Nissl staining and a caspase activity assay in the
      hippocampal cornu ammonis 1 sector, the nucleus reticularis thalami, and the
      striatum. At 24 hrs, 3 days, and 7 days, animals were tested according to a
      neurologic deficit score. MEASUREMENTS AND MAIN RESULTS: In all groups, typical
      delayed neurodegeneration was observed in selective vulnerable brain areas.
      Neuroscore, TUNEL, and Nissl staining revealed no relevant differences between
      the groups (BDNF vs. placebo) with regard to neurologic recovery and the number
      of viable (after 7 days in cornu ammonis 1 sector: BDNF, 110 +/- 32; placebo, 142
      +/- 53) and TUNEL-positive neurons (after 7 days in cornu ammonis 1 sector: BDNF,
      360 +/- 81; placebo, 253 +/- 62) during the different time points. CONCLUSIONS:
      Despite the well-known neuroprotective properties of BDNF in ischemic-induced
      neuronal degeneration, the present study did not reveal any beneficial effects
      regarding neurologic recovery and neurohistopathologic outcome after global
      cerebral ischemia in rats. Future investigations should focus on intracellular
      signaling cascades activated by BDNF after global cerebral ischemia.

PMID- 15508661
TI  - Miniaturized chest compressor.
AB  - BACKGROUND: Current American Heart Association guidelines call for continuous
      manual chest compressions for cardiopulmonary resuscitation. Chest compressions
      maintain critical levels of forward blood flow, including blood flow to the
      myocardium during cardiac arrest, to allow for successful resuscitation. The
      demand on rescuers is to ensure that compression is consistent, with appropriate
      force and depth, often under difficult conditions of rescue, evacuation, and
      transport. It is also of great moment that fatigue of the rescuer adversely
      affects outcomes. This evaluation was to compare two pneumatically driven
      devices, the Michigan Thumper (Michigan Instruments, Grand Rapids, MI), as an
      industrial standard, and the miniaturized chest compressor. METHODS: On a porcine
      model of cardiopulmonary resuscitation, alternating current fibrillation was
      induced for 7 mins, followed by 5 mins of chest compression. Arterial and right
      atrial pressures and end-tidal CO2 were measured. Coronary perfusion pressure was
      calculated as the difference between compression end-diastolic arterial pressure
      and right atrial pressure. RESULTS: Threshold levels of coronary perfusion
      pressure (>15 mm Hg) and end-tidal CO2 (>10 mm Hg) for successful defibrillation
      were maintained with the miniaturized chest compressor. Consistently greater
      coronary perfusion pressure and end-tidal CO2 values were achieved with the
      miniaturized chest compressor in comparison with the Thumper. CONCLUSION: The
      miniaturized chest compressor has the important potential advantage of minimal
      weight and, therefore, portability, without any reduction in effectiveness. To
      the contrary, it is potentially more effective than the much larger and heavier
      industry standard for maintaining circulation.

PMID- 15508662
TI  - A new method for inducing hypothermia during cardiac arrest.
AB  - OBJECTIVE: It has been shown that hypothermia induced after successful
      resuscitation of comatose survivors of ventricular fibrillation cardiac arrest
      improves survival and neurologic function. Recent studies also suggest that
      earlier induction of hypothermia may yield even more improvement. We sought to
      determine if a new pump system, in addition to vigorous external chest
      compression, could rapidly induce hypothermia during cardiopulmonary
      resuscitation in a porcine model of cardiac arrest. METHODS: Nine pigs (25-37 kg)
      were instrumented with micromanometers and thermocouple probes. Two 8-Fr
      catheters were placed into the femoral veins. Cardiac arrest was induced with 60
      Hz current. After 5 mins of no support, chest compression was performed by a
      circumferential pneumatic bladder (vest-cardiopulmonary resuscitation). Blood was
      withdrawn from one catheter by a pump system that maximized flow by servo-control
      of inlet pressure, was cooled, and was returned through the other catheter. Four
      dogs were instrumented similarly, and cooling was performed during normal
      circulation. RESULTS: In the pigs, baseline temperatures were (mean +/- SEM) 37
      +/- 1 degree C. With blood cooling in the external chiller to 10 degrees C,
      cerebral and right atrial temperatures were reduced by 0.49 +/- 0.09 and 0.67 +/-
      0.21 degrees C/min, respectively, for 10 mins. With blood cooling in the external
      chiller to 4 degrees C, cerebral and right atrial temperatures were reduced by
      0.61 +/- 0.18 and 1.56 +/- 0.33 degrees C/min, respectively. Cerebral cooling
      lagged behind right atrial cooling. There was a strong correlation between
      coronary perfusion pressure (aortic to right atrial mean decompression-phase
      pressure) and cerebral cooling rate (r = .79; p < .022). Rates of cooling during
      normal circulation in dogs were similar. CONCLUSIONS: Rapid induction of mild
      hypothermia is feasible with a system that uses venous access, standard access
      techniques, and external chest compression. Induction of mild hypothermia during
      cardiac arrest in the field appears feasible and may allow the benefit of very
      early induction of hypothermia to be determined in patients.

PMID- 15508663
TI  - Secondary confirmation of endotracheal tube position by ultrasound image.
AB  - OBJECTIVE: Secondary confirmation of endotracheal (ET) tube position by
      ultrasound image. DESIGN: Prospective, randomized study. SETTING: A medical
      center-based tertiary pediatric intensive care unit. PATIENTS: A total of 59
      patients aged from newborn to 17 yrs old underwent ET tube insertion because of
      cardiopulmonary arrest or impending respiratory failure. INTERVENTION: Ultrasound
      imaging was performed immediately before and after the ET tube placement
      procedure. The most frequently used ultrasonic scanning window was the subxiphoid
      window at the mid-upper abdominal, just beneath the xiphoid process and the lower
      margin of liver. The sector angle was set as wide as possible (90 degrees) so
      that the bilateral diaphragm could be well scanned. MEASUREMENTS AND MAIN
      RESULTS: Using the ultrasound imaging method, we successfully identified all of
      two esophageal intubations and eight incidents of initial ET tube misplacement,
      which had been positioned down to the right main bronchus. Finally, we
      successfully identified all 59 of the correct placements of ET tubes in the
      trachea. CONCLUSIONS: Ultrasound imaging of diaphragm motion is a useful, quick,
      noninvasive, portable, and direct anatomic method for assessment of ET tube
      position. We think it should be considered the method of choice for the secondary
      confirmation of the ET tube position.

PMID- 15508664
TI  - Nonselective beta-blocking agent improves the outcome of cardiopulmonary
      resuscitation in a rat model.
AB  - OBJECTIVE: Postresuscitation myocardial dysfunction has been recognized as a
      leading cause of early death after initial successful resuscitation. Recent
      experimental and clinical studies have indicated that the beta-adrenergic effect
      of epinephrine significantly increases the severity of postresuscitation
      myocardial dysfunction. The fact that beta-adrenergic stimulation increases
      myocardial oxygen consumption during ventricular fibrillation is an important
      implication with respect to both the exogenous in terms of pharmacologic
      interventions during cardiopulmonary resuscitation and the endogenous as the
      result of intense sympathetic activation of cardiovascular collapse. Earlier
      experimental evidence has indicated that oxygenation improved by beta-blockade
      and beta1-blocking agent did offset the adverse effect of epinephrine. This
      prompted us to investigate the effect of beta-blockade on both exogenous and
      endogenous beta stimulation in an established rat model. DESIGN: Prospective,
      randomized, controlled study. SETTING: Animal research laboratory. SUBJECTS: Male
      Sprague-Dawley rats. INTERVENTIONS: In this series of studies, propranolol was
      administrated before ventricular fibrillation as a pretreatment combined with
      epinephrine treatment during precordial compression and then alone in a prolonged
      cardiac arrest setting. MEASUREMENTS AND MAIN RESULTS: Improved postresuscitation
      myocardial dysfunction (cardiac index, dP/dt40, -dP/dt) was observed with
      propranolol, a nonselective beta-adrenergic blocker, in pretreated animals such
      that the beneficial effects were associated with better postresuscitation
      survival. CONCLUSION: Nonselective beta-blockade improved the outcome of
      cardiopulmonary resuscitation in a rat model and deserves further evaluation in
      settings of cardiopulmonary resuscitation.

PMID- 15508665
TI  - Hemodynamics associated with breathing through an inspiratory impedance threshold
      device in human volunteers.
AB  - OBJECTIVE: Increased negative intrathoracic pressure during spontaneous
      inspiration through an impedance threshold device (ITD) causes elevated arterial
      blood pressure in humans. This study was performed to determine whether the acute
      increase in blood pressure induced by breathing through an ITD is associated with
      increased stroke volume and cardiac output. DESIGN: Randomized, blinded,
      controlled trial. SETTING: Laboratory. SUBJECTS: Ten women and ten men.
      INTERVENTIONS: We measured hemodynamic and respiratory responses during two
      separate ITD conditions: 1) breathing through a face mask with an ITD (impedance
      of 6 cm H2O [0.59 kPa]) and 2) breathing through the same face mask with a sham
      ITD (control). Stroke volume was measured by thoracic bioimpedance. MEASUREMENTS
      AND MAIN RESULTS: Compared with the control condition, ITD produced higher stroke
      volume (124 +/- 3 vs. 137 +/- 3 mL; p = .013), heart rate (63 +/- 3 vs. 68 +/- 3
      beats/min; p = .049), cardiac output (7.69 vs. 9.34 L/min; p = .001), and
      systolic blood pressure (115 +/- 2 to 122 +/- 2 mm Hg [15.33 +/- 0.3 to 16.26 +/-
      0.3 kPa]; p = .005) without affecting expired minute ventilation (6.2 +/- 0.4 to
      6.5 +/- 0.4 L/min; p = .609). CONCLUSIONS: Breathing with an ITD at relatively
      low impedance increases systolic blood pressure by increasing stroke volume and
      cardiac output. The ITD may provide short-term protection against cardiovascular
      collapse induced by orthostatic stress or hemorrhage.

PMID- 15508666
TI  - Body weight does not affect defibrillation, resuscitation, or survival in
      patients with out-of-hospital cardiac arrest treated with a nonescalating
      biphasic waveform defibrillator.
AB  - BACKGROUND: This is a study of the influence of body weight on defibrillation,
      resuscitation, and survival in patients with out-of-hospital cardiac arrest
      treated with a nonescalating impedance-compensating 150-J biphasic waveform
      defibrillator. METHODS: Cardiac arrest data from Rochester, MN, emergency medical
      services over a 6-yr period was retrospectively analyzed. Patient weight data
      were available for 62 of the 68 patients who were treated initially by basic life
      support personnel and who presented with a shockable rhythm. For each
      defibrillation and resuscitation outcome variable, we tested for differences in
      body weight for successful vs. unsuccessful outcome. RESULTS: Initial shocks
      defibrillated 92% (83% to 97%) of patients. Cumulative success with two shocks
      was 98% (confidence interval, 92% to 100%) and with three shocks was 100%
      (confidence interval, 95% to 100%). The mean shock impedance was 90 +/- 21 ohms.
      The average body weight was 84 +/- 17 kg (minimum, 53 kg; maximum, 135 kg) and
      was normally distributed. Based on the body mass index for 46 patients,
      approximately 41% were classified as overweight (body mass index, > or = 25), 24%
      obese (body mass index, > or = 30), and 4% extremely obese (body mass index, > or
      = 40). The remaining 31% were classified as normal or underweight. First-shock
      success, cumulative success through two shocks, and cumulative success through
      the first-shock series were unrelated to body weight, as were basic life support
      restoration of spontaneous circulation, prehospital restoration of spontaneous
      circulation, hospital admission, and discharge. CONCLUSIONS: Overweight patients
      were defibrillated by the biphasic waveform used in this study at high rates,
      with a fixed energy of 150 J, and without energy escalation.

PMID- 15508667
TI  - Effect of vasopressin on postresuscitation ventricular function: unknown
      consequences of the recent Guidelines 2000 for Cardiopulmonary Resuscitation and
      Emergency Cardiovascular Care.
AB  - OBJECTIVE: To compare the effect on postresuscitation left ventricular function
      of vasopressin vs. epinephrine used during cardiopulmonary resuscitation in a
      swine model of prolonged prehospital ventricular fibrillation. DESIGN:
      Prospective, randomized experimental study. SETTING: University large animal
      resuscitation research laboratory. SUBJECTS: Forty-eight swine (29 +/- 1 kg).
      INTERVENTIONS: Resuscitation after 12.5 mins of untreated ventricular
      fibrillation, randomizing animals during cardiopulmonary resuscitation to
      treatment with epinephrine, vasopressin, or vasopressin followed by a vasopressin
      antagonist administered in the postresuscitation period. MEASUREMENTS AND MAIN
      RESULTS: Serial measurements of left ventricular systolic and diastolic function
      (prearrest, postresuscitation at 30 mins and 6 hrs) and 24-hr survival. Animals
      receiving vasopressin had more postresuscitation left ventricular dysfunction
      than those receiving epinephrine (p < .05). The vasopressin antagonist produced
      vasodilation and improved early postresuscitation left ventricular systolic and
      diastolic function but did not have a lasting effect on such postresuscitation
      ventricular function and decreased 24-hr survival compared with the use of
      vasopressin alone (3/16 vs. 10/16 survivors; p < .05). CONCLUSIONS: Vasopressin
      use during cardiopulmonary resuscitation results in worse postresuscitation left
      ventricular function early but did not compromise 24-hr outcome. Reversal of
      vasopressin's effect with a specific V-1 antagonist in the postresuscitation
      period did not improve survival.

PMID- 15508668
TI  - Spontaneous breathing through an inspiratory impedance threshold device augments
      cardiac index and stroke volume index in a pediatric porcine model of hemorrhagic
      hypovolemia.
AB  - BACKGROUND: Hemorrhagic shock secondary to trauma is associated with poor
      survival. The impedance threshold device (ITD) has been shown to improve blood
      pressure and survival rates in an adult porcine model of hemorrhagic hypovolemia.
      Pediatric hemodynamics, anatomy, and physiology differ from adults. Evaluation of
      the ITD has not been previously assessed in a pediatric porcine model of
      hypovolemia induced by hemorrhage. OBJECTIVE: To determine whether ITD-assisted
      breathing, with and without positive end-expiratory pressure, will improve key
      hemodynamic parameters following hypovolemia induced by hemorrhage in a pediatric
      porcine model. METHODS: Intubated, anesthetized, hemodynamically stable,
      spontaneously breathing piglets were rapidly bled 40% of their calculated blood
      volume. Piglets' hemodynamic and intrathoracic pressures were continuously
      monitored during 10-min normovolemic baseline, bleed to hypotensive baseline, 10
      min ITD-assisted breathing, 10 mins without ITD, 10-min ITD-assisted breathing
      randomized with or without positive end-expiratory pressure (3 cm H2O), 10 mins
      without ITD, reinfusion of shed blood, 10-min baseline following return to
      normovolemia. The ITD had an inspiratory cracking pressure of -7 cm H2O.
      Transthoracic echocardiographic parameters were measured at the end of each 10
      min period. RESULTS: There was no significant difference in baseline assessments
      between groups. Systolic blood pressure, cardiac index, and stroke volume index
      were significantly greater during ITD-assisted breathing. There was a trend
      toward increased left ventricular end-diastolic dimension during ITD use. Heart
      rate, systemic vascular resistance index, left ventricular end-systolic
      dimension, and shortening fraction did not change significantly during ITD
      assisted breathing. There was equivalent improvement in systolic blood pressure,
      cardiac index, and stroke volume index, when the ITD alone and ITD plus positive
      end-expiratory pressure were used. CONCLUSIONS: ITD-assisted breathing
      significantly augmented systolic blood pressure, cardiac index, and stroke volume
      index in this pediatric porcine model of hemorrhagic hypovolemia. These effects
      appear related to increased left ventricular preload and not by increased
      systemic vascular resistance or heart rate. These beneficial effects of ITD
      assisted breathing are not changed by the addition of positive end-expiratory
      pressures of 3 cm H2O.

PMID- 15508669
TI  - Human factors impact successful lay person automated external defibrillator use
      during simulated cardiac arrest.
AB  - OBJECTIVE: With the dissemination of automated external defibrillators in the
      community, there is increasing lay person use, along with less formal automated
      external defibrillator training and retraining. Therefore, the "ease of use"
      factors related to the human-device interface may be vital for successful use. We
      sought to determine whether human factor differences would result in differences
      in parameters of successful or safe use by lay persons in the setting of
      simulated cardiac arrest. METHODS: We measured parameters of successful and safe
      use with two automated external defibrillator devices among two groups of
      volunteers, those trained with a brief video tape and those without any training
      (completely naive). Both devices (the Philips FR2 or the HS1) are used in public
      access defibrillator settings. Volunteers entered a mock cardiac arrest scenario
      after randomization to either the naive (untrained) group or to a video-trained
      group. RESULTS: Both the FR2 and HS1 were found to be completely safe when used
      by video-trained and by naive groups of participants, with no adverse events
      observed (total, n = 256). For both devices, video-trained participants
      demonstrated high rates of successful defibrillation in the simulated testing
      (86% for FR2 and 89% for HS1). With the FR2, video-trained participants were
      significantly more successful compared with naive, untrained participants (86%
      vs. 48% successful use; p < .001). However, for the HS1, there was no significant
      difference in success rates for the video-trained vs. naive, untrained groups
      (89% vs. 87%; p = .79). CONCLUSIONS: Both devices are safe with either video
      trained or naive users. The successful use of each device is high when
      participants view the training videotape designed for the device. An important
      difference in successful use was observed for naive users where the HS1 showed
      improved successful use compared with the FR2. Because defibrillation in the
      community may increasingly be attempted by lay persons whose training is remote
      or who have not been trained at all, the "naive" scenario may be increasingly
      relevant to automated external defibrillator use. Collectively, these data
      support the notion that human factors associated with ease of use may play a
      critical factor in survival rates achieved by specific devices.

PMID- 15508670
TI  - Detrimental hemodynamic effects of assisted ventilation in hemorrhagic states.
AB  - OBJECTIVE: Our goal was to demonstrate explicitly that lower-frequency positive
      pressure ventilation not only preserves adequate oxygenation and acid-base status
      in hemorrhagic states, but also that "normal" or higher respiratory rates
      significantly compromise hemodynamics, even with moderate degrees of hemorrhage.
      DESIGN AND SUBJECTS: Eight intubated pigs (ventilated with 12 mL/kg tidal volume,
      28% FIO2, respiratory rate = 12 breaths/min) were hemorrhaged to <65 mm Hg of
      systolic blood pressure. Respiratory rates were then sequentially changed every
      10 mins to 6, 20, 30, and 6 breaths/min. MEASUREMENTS AND MAIN RESULTS: With
      respiratory rates at 6 breaths/min, all subjects maintained pH of >7.25 and SaO2
      of >99% while increasing systolic blood pressure (mean, 65-84 mm Hg; p < .05),
      time-averaged coronary perfusion pressure (50 +/- 2 to 60 +/- 4 mm Hg; p < .05),
      and cardiac output (2.4 to 2.8 L/min; p < .05). With respiratory rates of 20 and
      30 breaths/min, systolic blood pressure (73 +/- 4 and 66 +/- 5 mm Hg,
      respectively), coronary perfusion pressure (47 +/- 3 and 42 +/- 4 mm Hg), and
      cardiac output (2.5 and 2.4 L/min) diminished. When returned to 6 breaths/min,
      systolic blood pressure (95 mm Hg), coronary perfusion pressure (71 + 6 mm Hg),
      and cardiac output (3.0 L/min) improved significantly (p < .05 for all
      comparisons). CONCLUSIONS: After moderate hemorrhage, animals maintain adequate
      oxygenation and acid-base status with lower-frequency respiratory rates, whereas
      increasingly higher respiratory rates progressively and significantly impair
      hemodynamics. Current ventilatory protocols for trauma resuscitation should be re
      examined and considered a possible cause of worsened clinical outcomes and
      unrecognized confounded study results.

PMID- 15508671
TI  - Wide variation in cardiopulmonary resuscitation interruption intervals among
      commercially available automated external defibrillators may affect survival
      despite high defibrillation efficacy.
AB  - OBJECTIVE: Recent studies have associated interruptions of cardiopulmonary
      resuscitation imposed by automated external defibrillators (AEDs) with poor
      resuscitation outcome. In particular, the "hands-off" interval between precordial
      compressions and subsequent defibrillation shock has been implicated. We sought
      to determine the range of variation among current-generation AEDs with respect to
      this characteristic. MEASUREMENTS: Seven AEDs from six manufacturers were
      characterized via stopwatch and arrhythmia simulator with respect to the imposed
      hands-off interval. All AEDs were equipped with new batteries, and measurements
      were repeated five times for each AED. MAIN RESULTS: A wide variation in the
      hands-off interval between precordial compressions and shock delivery was
      observed, ranging from 5.2 to 28.4 secs, with only one AED achieving an
      interruption of <10 secs. Laboratory and clinical data suggest that this range of
      variation could be responsible for a more than two-fold variation in patient
      resuscitation success, an effect that far exceeds any defibrillation efficacy
      differences that may hypothetically exist. CONCLUSIONS: In addition to
      defibrillation waveform and dose, researchers should consider the hands-off
      cardiopulmonary resuscitation interruption interval between cardiopulmonary
      resuscitation and subsequent defibrillation shock to be an important covariate of
      outcome in resuscitation studies. Defibrillator design should minimize this
      interval to avoid potential adverse consequences on patient survival.

PMID- 15508672
TI  - Induced hypothermia by central venous infusion: saline ice slurry versus chilled
      saline.
AB  - OBJECTIVE: Surface cooling improves outcome in selected comatose survivors of
      cardiac arrest. Internal cooling with considerable volumes of intravenous cold
      saline may accelerate hypothermia induction. This study compares core
      temperatures in swine after central catheter infusions of saline ice slurry
      (saline with smoothed 100-microm-size ice particles) vs. an equal volume of
      chilled saline. We hypothesized that slurry would achieve core hypothermia (32-34
      degrees C) more consistently and at a faster rate. DESIGN: A total of 11 swine
      were randomized to receive microparticulate ice slurry, chilled saline infusion,
      or anesthesia alone in a monitored laboratory setting. INTERVENTIONS: Intravenous
      bolus (50 mL/kg) of slurry or chilled 1.5% NaCl saline. Slurry was composed of a
      1:1 mixture of ice and distilled H2O plus NaCl. MEASUREMENTS: Cerebral cortex,
      tympanic membrane, inferior vena cava, rectal temperatures, electrocardiogram,
      arterial blood pressure, and arterial oxygen saturation were recorded for 1 hr
      after bolus. MAIN RESULTS: Compared with anesthetized controls, core brain
      temperatures of the saline and slurry groups dropped by 3.4 +/- 0.4 degrees C and
      5.3 +/- 0.7 degrees C (p = .009), respectively. With an infusion rate of 120
      mL/min, cooling rates for the saline and slurry groups were -11.6 +/- 1.8 degrees
      C/hr and -18.2 +/- 2.9 degrees C/hr, respectively, during the first 20 mins. Four
      of four animals in the slurry group vs. zero of four animals in the saline group
      achieved target cortical temperatures of <34 degrees C. CONCLUSIONS: Cold
      intravenous fluids rapidly induce hypothermia in swine with intact circulation. A
      two-phase (liquid plus ice) saline slurry cools more rapidly than an equal volume
      of cold saline at 0 degrees C. Ice-slurry could be a significant improvement over
      other cooling methods when rate of cooling and limited infusion volumes are
      important to the clinician.

PMID- 15508673
TI  - Vasopressin during cardiopulmonary resuscitation: a progress report.
AB  - OBJECTIVE: In patients undergoing cardiopulmonary resuscitation, circulating
      endogenous vasopressin concentrations were significantly higher in successfully
      resuscitated patients than in patients who died. These observations have prompted
      several investigations to assess the role of vasopressin to improve
      cardiopulmonary resuscitation management. DESIGN: Literature review. RESULTS: In
      the cardiopulmonary resuscitation laboratory, vasopressin improved vital organ
      blood flow, cerebral oxygen delivery, the probability of restoring spontaneous
      circulation, and neurologic recovery better than epinephrine. In pediatric
      preparations with asphyxia, epinephrine was superior to vasopressin, whereas in
      both pediatric pigs with ventricular fibrillation and adult porcine models with
      asphyxia, combinations of vasopressin and epinephrine proved to be highly
      effective. In addition, vasopressin enabled short- and long-term survival in a
      porcine model of uncontrolled hemorrhagic shock. In a recently published
      European, multiple-center trial, 1,219 adult patients with out-of-hospital
      cardiac arrest were randomized to receive two injections of either 40 IU of
      vasopressin or 1 mg of epinephrine followed by additional epinephrine if needed.
      The clinical study did not confirm laboratory data showing vasopressin to be more
      effective than epinephrine in ventricular fibrillation and pulseless electrical
      activity, but vasopressin was superior to epinephrine in patients with asystole.
      Vasopressin followed by epinephrine was more effective than epinephrine alone in
      the treatment of refractory cardiac arrest. CONCLUSIONS: According to new data
      from the European vasopressin study, we suggest, first, the administration of 1
      mg of epinephrine, followed alternately by 40 IU of vasopressin and 1 mg of
      epinephrine every 3 mins in adult cardiac arrest victims, regardless of the
      initial electrocardiographic rhythm.

PMID- 15508674
TI  - Recurrent ventricular fibrillation in out-of-hospital cardiac arrest after
      defibrillation by police and firefighters: implications for automated external
      defibrillator users.
AB  - OBJECTIVE: To determine the prevalence and frequency of recurrent ventricular
      fibrillation (VF) in patients defibrillated by police and firefighters only and
      to determine its relation to survival. DESIGN: Retrospective observational study.
      SETTING: Out of hospital. PATIENTS: Individuals with witnessed VF arrest in the
      Rochester, MN, ambulance public service area who had defibrillatory shocks
      delivered by police and firefighters and return of spontaneous circulation with
      shocks only. MEASUREMENTS AND MAIN RESULTS: Electrocardiograms were recovered
      from data cards in automated external defibrillators used by police (n = 49) or
      firefighters (n = 18) to deliver shocks from December 1996 through December 2003
      in the Rochester, MN, ambulance public service area. Patients with witnessed VF
      arrest were identified for recurrent VF after initial shock success (first one to
      three shocks). Both police and firefighters deployed automated external
      defibrillators delivering nonescalating 150-J biphasic truncated exponential
      waveform shocks (ForeRunner Automated External Defibrillator,
      Phillips/Heartstream Operation, Seattle, WA). Among 67 patients, 30 (45%)
      survived to neurologically intact discharge (overall performance category score
      of 1 in 29 patients and score of 2 in one patient). Twenty-nine patients (43%)
      regained spontaneous circulation with shocks only and 25 of 29 (86%) survived. VF
      recurred in 35 of the 67 patients (52%) while being cared for by police or
      firefighters. Of these 35 patients, no relation was found between the prevalence
      or frequency of VF recurrence and survival. CONCLUSIONS: VF recurrence is
      frequent, variable in time of onset, and unrelated to the performance of
      bystander CPR. The prevalence and frequency of VF recurrence were unpredictable
      and do not adversely affect survival. Thus, vigilance for recurrent VF is
      essential to ensure the survival of patients who are in the care of first
      responders, even after initial restoration of pulses with shocks.

PMID- 15508675
TI  - Beta1-adrenergic blockade during cardiopulmonary resuscitation improves survival.
AB  - OBJECTIVE: The short-acting beta1-selective adrenergic blocking agent, esmolol,
      was administrated during cardiopulmonary resuscitation with the hypothesis that
      initial resuscitation and postresuscitation survival would be improved. DESIGN:
      Prospective, randomized, controlled study. SETTING: Animal research laboratory.
      SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Ventricular fibrillation was
      induced in 18 male Sprague-Dawley rats, which were then left untreated for 6 mins
      before attempted resuscitation with precordial compression, mechanical
      ventilation, and electrical defibrillation. Animals were randomized to receive
      300 microg/kg esmolol in a volume of 200 microL or an equivalent volume of saline
      placebo during cardiopulmonary resuscitation. Electrical defibrillation was
      attempted after 12 mins of ventricular fibrillation. MEASUREMENTS AND MAIN
      RESULTS: Esmolol-treated animals required a significantly smaller number of
      electrical shocks before resuscitation. Each of the esmolol-treated but only five
      of nine placebo-treated animals were successfully resuscitated. Postresuscitation
      contractile and left ventricular diastolic functions of resuscitated animals were
      significantly better after esmolol administration and duration of survival was
      significantly increased. CONCLUSIONS: A short-acting beta1-selective adrenergic
      blocking agent, when administered during cardiopulmonary resuscitation,
      significantly improved initial cardiac resuscitation, minimized postresuscitation
      myocardial dysfunction, and increased the duration of postresuscitation survival.

PMID- 15508676
TI  - Look before you sign.

PMID- 15508677
TI  - Laser-assisted uvulopalatoplasty for the treatment of snoring.
AB  - Snoring is seldom discussed outside of the household. Unfortunately, snoring can
      be a sign of a life-threatening disease called obstructive sleep apnea, or, OSA.
      This article helps dentists detect OSA early by paying attention to subtle
      findings during routine oral exams, asking pertinent questions and, finally,
      making a referral to specialists who are trained and experienced in treating
      these cases. The article also delineates a range of treatment modalities,
      including laser-assisted uvulopalatoplasty and its modification.

PMID- 15508678
TI  - Sublingual salivary gland enlargement.
AB  - When examining the mouth floor, sublingual salivary gland enlargement, or
      hypertrophy, is commonly seen by dentists. It represents an innocuous,
      asymptomatic lesion that tends to proliferate into edentulous areas. It is often
      mistaken for a pathologic entity. Recognition avoids concern, misdiagnosis and
      unnecessary surgery.

PMID- 15508679
TI  - Wireless local area network for the dental office.
AB  - Dental offices are no exception to the implementation of new and advanced
      technology, especially if it enhances productivity. In a rapidly transforming
      digital world, wireless technology has a special place, as it has truly "retired
      the wire" and contributed to the ease and efficient access to patient data and
      other software-based applications for diagnosis and treatment. If the office or
      the clinic is networked, access to patient management software, imaging software
      and treatment planning tools is enhanced. Access will be further enhanced and
      unrestricted if the entire network is wireless. As with any new, emerging
      technology, there will be issues that should be kept in mind before adapting to
      the wireless environment. Foremost is the network security involved in the
      installation and use of these wireless networks. This short, technical manuscript
      deals with standards and choices in wireless technology currently available for
      implementation within a dental office. The benefits of each network security
      protocol available to protect patient data and boost the efficiency of a modern
      dental office are discussed.

PMID- 15508680
TI  - Current concepts in gutta-percha removal in endodontic retreatment.
AB  - Effective removal of gutta-percha (GP) in endodontic retreatment is a significant
      factor in creating successful outcomes from failed procedures. Ideally, gutta
      percha removal must be efficient, not predispose the tooth to subsequent failure
      through iatrogenic events, and clean the existing canals so that subsequent
      irrigants can effectively and biomechanically cleanse the root canal system. All
      things being equal, it is recommended that GP be removed without solvents in the
      coronal two-thirds of canals as much as possible and with solvents in the apical
      third. Rotary nickel titanium files and the SystemB heat source (SybronEndo,
      Orange, CA) are significant adjuncts in effective GP removal.

PMID- 15508681
TI  - The dental health of President John Adams.
AB  - The oral health of George Washington has been widely studied and written about.
      Not so, however, with our second president, John Adams, whose dental health was
      apparently poor throughout his life. His pernicious habit of inducing vomiting to
      treat various bodily ills, coupled with a great love of sweets, led to the loss
      of his teeth, which he stubbornly refused to replace with dentures. When he was
      older, this led to his speech being so badly affected, that he could barely be
      understood.

PMID- 15508682
TI  - Putting hope into action.

PMID- 15508683
TI  - Caring and sharing. As the community care model of treating patients takes hold,
      physicians gain big from using a PM/EMR systems network and from sharing patient
      information electronically.

PMID- 15508684
TI  - Business not as usual. Washington State community provider stretches an automated
      order entry system--and expands its functionality to include automation for
      referral management.

PMID- 15508685
TI  - Medication transformation: pharmacists on the floor. A Midwest healthcare system
      takes bar code technology to new heights, as part of an enterprise initiative to
      optimize patient safety.

PMID- 15508686
TI  - The vale of speed-to-value. How well health plans in flux can optimize
      operational efficiency often hinges on the IS and change strategies they employ.

PMID- 15508687
TI  - Data center upgrade essential to enhanced patient care. As digital applications
      expand to physicians, nurses and patients, healthcare providers require greater
      data availability and security to reduce error rates, risks and costs.

PMID- 15508688
TI  - Evolution of care management systems integration. Functional integration and
      comprehensive patient information build on the cost savings and competitive
      advantages introduced by technical integration.

PMID- 15508689
TI  - The case for standards. Uniform physician credentialing process can save
      physician practices and hospitals time, money and frustration.

PMID- 15508690
TI  - Grand Central scheduling: case history. A hospital radiology department gains
      physician satisfaction and treatment efficiency with a centralized scheduling
      solution.

PMID- 15508691
TI  - Preparing for consumerism: the top 10. Health plans and providers alike should
      prepare for consumer-driven health plans with this list of 10 strategic
      imperatives.

PMID- 15508692
TI  - Rx for growing pains: case history. Clean data, consolidation and an e-commerce
      solution streamline the purchasing process at a Chicago healthcare network.

PMID- 15508693
TI  - Now hear this. Health plan's VoIP technology lets physician practices move to the
      front of the line for issues they can't resolve themselves using online self
      service.

PMID- 15508694
TI  - The enabling powers of SSO. A health plan's path to greater utilization of its
      Web site may rest with a familiar technology.

PMID- 15508695
TI  - Physician practice management HotList.

PMID- 15508696
TI  - It's more than a matter of trust.

PMID- 15508697
TI  - The OIIQ issues an advisory opinion to the Minister of Health and Social Services
      on the quality of nursing care at the CHSLD Centre-ville (Saint-Charles-Borromee
      and Manoir de l'Age d'Or residences).

PMID- 15508698
TI  - Code of Ethics of Nurses making enlightened decisions about overtime.

PMID- 15508701
TI  - [Analysis of changes in lower urinary tract symptoms with aging].
AB  - BACKGROUND: Urination disorders start to appear in an age-dependent fashion,
      which contribute to the degradation of quality of life (QOL) in erderly persons.
      This study focused on elucidating changes of the lower urinary tract symptoms
      (LUTS) and changing of voiding condition with aging in the subjects, who offered
      the health checks. METHODS: We evaluated urinary function in 225 Japanese males
      (age 20-79), estimated International prostate symptom score (IPSS), QOL score,
      uroflowmetry, prostate volume and residual urine (estimated from transabdominal
      ultrasonography). In addition, 539 females (age 20-89) were assigned IPSS and QOL
      scores. RESULTS: The distribution of severity of symptoms significantly changed
      with age in both sexes. QOL scores tended to increase in males, IPSS, prostate
      volume and residual urine were significantly increasing related to age, and
      advanced age was associated with a decline of voiding volume and Qmax. Comparison
      of QOL scores and IPSS criteria demonstrated a significantly positive correlation
      with incomplete emptying and a weak stream. A significant negative correlation
      was found between the QOL score and Qmax. The distribution of middle level of
      symptom, divided by clinical guideline for benign prostatic hyperplasia,
      significantly increased with age. On the other hand, in females, the QOL score
      seemed to be stable whilst there was a slight increase of IPSS. In contrast,
      frequency and incomplete emptying were significantly related to QOL scores.
      CONCLUSIONS: These investigations supported changing of lower urinary tract
      disorder with aging in both sexes. Since the approximate 50% of sixth and seventh
      decade males, classified to the middle level of symtom, which need treatment, the
      high incident of degradation of the LUTS with age, should predict for the future.

PMID- 15508700
TI  - [A clinical study of estramustine phosphate sodium for the treatment of hot
      flushes in men with prostate cancer].
AB  - PURPOSE: To assess the effectiveness and tolerability of estramustine sodium
      phosphate in men with hot flushes during combined androgen blockade (CAB) therapy
      for prostate cancer. PATIENTS AND METHODS: Seven men with moderate to severe hot
      flushes were received estramustine sodium phosphate. Treatment response was
      assessed by hot flush score. RESULTS: A significant reduction in the hot flush
      score was seen with all patients. No thromboembolic complications occurred in any
      patients. CONCLUSIONS: Estramustine sodium phosphate appears to be a promising,
      well-tolerated and useful therapy for men with hot flushes during CAB treatment
      for prostate cancer.

PMID- 15508699
TI  - [Reference ranges of total serum and free testosterone in Japanese male adults].
AB  - PURPOSE: To establish reference range of serum Total Testosterone (T-T) and Free
      Testosterone (F-T) in Japanese male adults. SUBJECTS AND METHOD: Among 1,172 male
      adults, who daily lived their healthy life, 1,143 subjects in the year range from
      20 to 77 years old, who had serum LH concentration within its reference range
      (For 20-70 years old: 1.1-25.9 mIU/mL), were selected. As diurnal rhythm of both
      T-T and F-T was observed, blood samples were collected in the morning when T-T
      and F-T concentration were relatively stable at their high concentration levels.
      The collected samples were stored at -20 degree C until they were used for
      assays. RESULTS: Reference range for T-T has decided to express by the mean +/-
      2SD calculated from the entire test results, because influence of aging on the
      results was negligible, Reference range of T-T has established as 2.01-7.50
      ng/mL. The other hand, reference ranges of F-T classified for every decade have
      decided to express by the mean +/- 2SD of each decade subgroup, because great
      influence of aging on F-T was observed. For each decade from 20 years on and > 70
      years, reference ranges of F-T have established as: 8.5-27.9 pg/mL, 7.6-23.1
      pg/mL, 7.7-21.6 pg/mL, 6.9-18.4 pg/mL, 5.4-16.7 pg/mL, and 4.5-13.8 pg/ mL,
      respectively. CONCLUSION: Reference ranges of serum T-T and F-T in Japanese male
      adults have established. And the value of Young Adult Mean (YAM) of F-T
      calculated for a group of the ages between 20 and 39 years have been proposed as
      a guideline of requirement for the Androgen Replacement Therapy (HRT). The value
      of 80% and 70% of YAM were 12.4 pg/mL and 10.9 pg/mL, respectively.

PMID- 15508702
TI  - [Primary undifferentiated carcinoma of the ureteral stump; a case report].
AB  - A 72-year-old man referred our hospital with the chief complaint of macroscopic
      hematuria. He had undergone simple left nephrectomy for left renal stone when he
      was 27-years-old. His urine cytology showed class IIIb. They were 4 times. We
      performed random biopsy of the bladder and retrograde pyelography of the right
      But they were no positive findings for the cause of hematuria and for the
      existence of malignancy. After 2 months, he had macroscopic hematuria again.
      Cystoscopic re-examination revealed a fibrin out of the residual left ureteral
      orifice. Computed tomographic scan showed a perivesical mass. The diagnosis was
      the carcinoma of the ureteral stump. We performed ureterectomy. The pathological
      study revealed the undifferentiated carcinoma. This case is the first report of
      the undifferentiated carcinoma occurred on the residual ureteral stump in the
      Japanese literature.

PMID- 15508703
TI  - [Cytomegalovirus infection in peptic ulcer in renal transplant recipient: a case
      report].
AB  - Gastroduodenal ulcers in renal transplant recipients are usually originated from
      excessive acid secretion or infection of Helicobacter pyroli. Herein, we report a
      case of cytomegalovirus (CMV)--induced gastric ulcer following cadaveric renal
      transplantation. The patient was a 48-year-old man with chronic renal failure and
      received cadaveric renal transplantation. A month later, he had epigastralgia
      without CMV-positive antigenemia and received gastrointestinal fiberscopy.
      Endoscopically, gastric ulcer was identified. Histological findings revealed
      conspicious nuclear enlargement of the non-epithelial cells in the ulcer bed,
      which indicated CMV infection. The patient was treated with ganciclovir for 2
      weeks and the symptom was relieved. He discharged with a good renal function on
      day 75 posttransplant. CMV infection plays an important role in gastric ulcer
      after renal transplantation. Antigenemia assay dose not seem feasible for the
      detection of CMV-induced gastric ulcer.

PMID- 15508704
TI  - [Biological significance in transposon-mediated mutation and molecular evolution-
      special reference to the junk DNA].

PMID- 15508705
TI  - [Diversification of genomes by SINEs and LINEs].

PMID- 15508706
TI  - [Retrotransposition mechanisms and adaptive behavior of telomere specific LINE].

PMID- 15508707
TI  - [Control of transposons by DNA methylation and RNAi].

PMID- 15508708
TI  - [DNA-based transposable elements as potential source of genome rearrangements in
      vertebrates].

PMID- 15508709
TI  - [The transposon-mediated gene trap method in Zebrafish].

PMID- 15508710
TI  - [Recent progress in mouse transposon research].

PMID- 15508711
TI  - [Prevention of parthenogenesis by genomic imprinting in mammals].

PMID- 15508713
TI  - [Rat genome sequencing and rat resources in Japan].

PMID- 15508712
TI  - [Cross-talk between signaling pathways in plants: controlling degradation of
      transcription factors is a key for cross-talk].

PMID- 15508714
TI  - [Recent movements in bioinformatics in India].

PMID- 15508715
TI  - [Phylogenetic analysis of two rabies viruses, Takamen and Komatsugawa strains
      isolated in Japan in the 1940's].
AB  - The entire coding region of the nucleoprotein (N) gene of Takamen and Komatsugawa
      strains of rabies virus isolated in Japan in 1940's were determined. Phylogenetic
      analysis was performed on 140 lyssaviruses (128 viruses of genotype 1 and 12
      lyssaviruses of other genotypes) isolated in various parts of the world,
      including the two Japanese rabies strains, based on the sequences of 1,350
      nucleotides of the N gene. The rabies viruses were divided into 12 distinct
      clusters at least, reflecting geographical areas and hosts as reservoirs. The
      Takamen, Nishigahara, and RC-HL strains derived from the Nishigahara strain were
      grouped into the same cluster as the Chinese strain (3aG) in the worldwide
      distribution group. The Komatsugawa strain was grouped into the same cluster as
      the viruses from a raccoon dog from Khabarovsk, and from a steppe fox in area of
      Lake Baikal in Russia in a group consisting of Canada, Greenland, and the Arctic.
      These data along with the historical evidence suggest that Japanese rabies
      viruses, the Takamen and Komatsugawa strains, belong to two different clusters
      and moved into Japan from China and Russia, respectively.

PMID- 15508716
TI  - [Bacterial interaction and indirect pathogenesis of Pseudomonas aeruginosa at the
      growth of MRSA].
AB  - Bacterial interactions such as methicillin-resistant Staphylococcus aureus (MRSA)
      growth inhibition or inactivation of anti-MRSA antibiotics by Pseudomonas
      aeruginosa as an indirect pathogen were tested by in vitro assay. Paired strains,
      P. aeruginosa and MRSA, used in this experiment were isolated from 63 respiratory
      samples at Juntendo University Hospital from 2002 to 2003. Growth inhibitory
      activities against MRSA by P. aeruginosa were tested with reversed agar plate
      method. Inactivation of anti-MRSA antibiotics by P. aeruginosa were assayed with
      disk diffusion method using agar over lay technique. Fifty-six (88.9%) out of 63
      samples showed the significant MRSA growth inhibitory activity by co-existed P.
      aeruginosa. Anti-MRSA antibiotics such as trimetoprim-sulfamethoxazole
      combination (ST), arbekacin (ABK) and minocycline (MINO) except Vancomycin (VCM)
      and Teicoplanin (TEIC) were inactivated by the co-existed P. aeruginosa. Our data
      suggests that P. aeruginosa may play not only as a chronic respiratory pathogen
      but also as an indirect pathogen. Further, the most P. aeruginosa with anti-MRSA
      activity isolated respiratory sample may play as a modulator of MRSA infection.

PMID- 15508717
TI  - [In vitro indirect pathogenesis of Pseudomonas aeruginosa against anti MRSA
      chemotherapy].
AB  - In the patient with a chronic respiratory disease, both Pseudomonas aeruginosa
      and methicillin-resistant Staphylococcus aureus (MRSA) are frequently detected
      from expectoration. Vancomycin (VCM) and arbekacin (ABK) are both recommended for
      the chemotherapy of MRSA infection in Japan. Minocycline (MINO) is also selected
      for the treatment of MRSA infection. While rifampicin (RFP) and a trimetoprim
      sulfamethoxazole combination (ST) are also recommended in Europe and USA but not
      recommended in Japan for the chemotherapy of MRSA infection. It is pointed out
      that coexistence bacteria affect chemotherapy as an indirect pathogen. Not only
      an antibacterial action but the immunological action or the metabolic effect
      against chronic P. aeruginosa infection such as DPB is known by the
      administration of 14-membered ring macrolides including erythromycin (EM). We
      considered the influence of P. aeruginosa isolated with MRSA on the activity
      against anti-MRSA agents by the disk diffusion method with bilayer flat agar in
      vitro. Moreover, we also examined the influence of EM against the activity of the
      anti-MRSA agents when P. aeruginosa was coexistence. One strain of MRSA as an
      indicator strain and 100 strains of P. aeruginosa as test strains, which were
      obtained from clinical materials, were used for the following experiment. P.
      aeruginosa was streaked on to the Mueller-Hinton agar culture medium (MHA), and
      they incubated at 35 degrees C for 24 hours. Then, the blood agar plate was piled
      up, MRSA was streaked on the blood agar surface, the susceptibility test disks
      (VCM, ABK, MINO, RFP, ST) were put on it, and incubated at 35 degrees C for a
      further 24 hours. The diameter of the zone of inhibition around the
      susceptibility disks against MRSA was measured and compared with P. aeruginosa
      free experiments. The anti-MRSA activity of MINO, ST and ABK was reduced by
      coexistence of P. aeruginosa. In RFP and VCM, the anti-MRSA activity was
      reinforced by coexistence of P. aeruginosa. Although the anti-MRSA activity of ST
      and ABK has improved by EM addition in the MHA plates, the anti-MRSA activity has
      not improved in MINO. These results are suggesting that in a MRSA infection, the
      chemotherapy by anti-MRSA agents were affected by coexistence of P. aeruginosa as
      an indirect pathogen. The macrolides such as EM may be useful as a modulator for
      chemotherapy by ST or ABK when MRSA and P. aeruginosa are isolated at the same
      time from the patient.

PMID- 15508718
TI  - [Molecular epidemiology of Haemophilus influenzae strains isolated from patients
      with meningitis during 1999 to 2003].
AB  - A total of 535 Haemophilus influenzae strains from 226 Japanese institutions
      participating in the Nationwide Surveillance Study Group for Bacterial Meningitis
      were sent to our laboratory during 1999 to 2003. All strains were analyzed by PCR
      to identify the beta-lactam resistance genes, and their susceptibilities to beta
      lactam agents were determined. These strains were classified into 6 genotype
      patterns and MIC90 values for ampicillin (ABPC): (i) beta-lactamase nonproducing,
      ABPC susceptible (BLNAS) strains and lacked all resistance genes (27.7% of
      isolates; MIC90, 0.5 microg/ml); (ii) beta-lactamase producing, ABPC resistant
      (BLPAR) strains (12.9%, 16 microg/ml); (iii) beta-lactamase nonproducing, ABPC
      resistant (Low-BLNAR) strains with a Asn526Lys amino acid substitution in ftsI
      gene encoding PBP3 (31.2%, 2 microg/ml); (iv) beta-lactamase nonproducing, ABPC
      resistant (BLNAR) strains with Ser385Thr and Asn526Lys substitutions in ftsI
      (17.2%, 8 microg/ml); (v) amoxicillin/clavlanic acid resistant (BLPACR I)
      strains, having beta-lactamase gene and a Asn526Lys amino acid substitution in
      ftsI (9.2%, 32 microg/ml); and (vi) amoxicillin/clavlanic acid resistant (BLPACR
      II), having beta-lactamase gene and ftsI substitutions as for BLNAR strains
      (1.9%, 64 microg/ml). All but 4 strains were serotype b. The prevalence of BLNAR
      strains has increased exponentially: 0% (n = 0/41) in 1999, 5.8% (n = 4/69) in
      2000, 14.1% (n = 19/139) in 2001, 20.1% (n = 32/159) in 2002, and 29.1% (n =
      37/127) in 2003. The MIC90s of BLNAR isolates except for ABPC were as follows:
      piperacillin, 0.125 microg/ml; ceftriaxone, 0.25 microg/ml; meropenem, 0.5
      microg/ml; cefotaxime, 1 microg/ml; panipenem, 2 microg/ml; cefozopran, 16
      microg/ml; and cefotiam, 64 microg/ml. To prevent such resistance from
      increasing, expedited vaccination, correct identification of the BLNAR
      molecularly, and the proper selection of proper antibiotics based on PK/PD must
      be taken.

PMID- 15508719
TI  - [Appropriate use of rapid diagnostic testing for influenza].
AB  - To determine a more timely acquisition of accurate results for influenza
      patients, a rapid diagnostic testing for influenza were studied on 877 pediatric
      patients performed during the 2002-2003 flu season in our hospital. Of these, 337
      patients were finally diagnosed as influenza based on the test results and
      treated with antiviral agents, amantadine or oseltamivir. Ten (29%) of the 34
      patients whose tests were negative within 12 hours after onset became positive
      over 12 hours after onset. On the other hand, diagnoses based on antigen tests
      over 12 hours after onset were reliable because all 13 patients first confirmed
      negative were unchanged when tested afterward. These 10 patients missed the
      opportunity to take antivirals early, which possibly caused them to have
      significantly longer (p = 0.0003) febrile duration and higher frequency of
      admission (p < 0.0001) than the 106 patients first confirmed positive within 12
      hours after onset. Days from onset until starting antivirals (mean 1.4 days), the
      febrile duration (mean 2.7 days) and frequency of hospitalization (20.5%) of the
      219 patients who tested positive over 12 hours after onset were significantly
      worse (p < 0.0001, p < 0.0001 and p = 0.0406, respectively) than those of
      patients testing positive within 12 hours after onset (mean 0.2 days, mean 1.7
      days and 11.3%, respectively). The febrile duration (mean 2.3 days) of the
      patients confirmed positive even over 12 hours, but within 48 hours, of onset was
      tolerable but significantly longer (p < 0.0001) than that of patients confirmed
      positive within 12 hours after onset. The frequency (19.6%) of hospitalization of
      the patients confirmed positive even over 12 hours, but within 48 hours, of onset
      was not significantly different from that of patients confirmed positive within
      12 hours after onset. These results suggested that over 12 hours but within 48
      hours after onset of illness is the best period for the rapid diagnosis to
      correctly determine whether a patient should be treated with antiviral agents
      based on the result.

PMID- 15508720
TI  - [Epidemiological study of methicillin-resistant Staphylococcus aureus isolated
      from the urology ward in 2003--nosocomial infection and community-acquired
      infection].
AB  - Methicillin-Resistant Staphylococcus aureus (MRSA) strains with the exception of
      urinary strains were isolated from the inpatients in urology ward hospitalized in
      2003 and medical workers. Biotype according to the production of coagulase,
      enterotoxin and mupirocin sensitivity, and genotype by pulsed field gel
      electrophoresis (PFGE), and clinical background were determined for the MRSA
      strains to analyze the transmission route of the infection. In 34 medical workers
      in urology ward, MRSA were isolated in 6 (17.6%) workers from the nasal cavity,
      and the rate of colonization in doctors was higher than in nurses. Furthermore,
      mupirocin-resistant strains were isolated from two medical workers. 18 MRSA
      strains were isolated in 2003 and the accounting was 8 strains from wounds, 6
      strains from sputum or nasal cavity, 3 strains from blood, and 2 strains from
      urinary tract. Most of the patients with MRSA had operations under general
      anesthesia or were under severe conditions with malignant tumors. No MRSA was
      detected at the same time from the same rooms. There were some rooms in which the
      MRSA detected rate was high, however no MRSA was isolated from hospital
      environments and dumping bacteria. These results suggest that the involvement of
      the medical workers and the spread of MRSA in the society might be important as
      infection source and for transmission of MRSA in hospital.

PMID- 15508721
TI  - [Evaluation of flow-through immunoassay for rapid detection of influenza A and B
      viruses].
AB  - We evaluated a flow-through immunoassay for rapid detection of influenza A and B
      viral antigens, RapidTesta FLU AB (Daiichi Pure Chemicals Co., Ltd., Tokyo,
      Japan), by using 507 specimens collected from patients with influenza-like
      symptoms during the 2002/2003 influenza season in Japan. The specimens consisted
      of 239 nasal swabs and 268 nasal aspirates; 374 specimens were collected from
      pediatric patients (under 16 years of age) and 133 from adult patients.
      RapidTesta FLU AB was compared with cell culture and nested reverse transcription
      polymerase chain reaction (RT-PCR). Cell culture detected influenza virus from
      66.7% of the 507 specimens (influenza AH3: 44.0%, B: 22.7%). For nasal swabs, it
      had a sensitivity of 81.9% (77/94), a specificity of 97.9% (142/145) and an
      efficiency of 91.6% (219/239) for influenza A virus as well as a sensitivity of
      80.0% (52/65), a specificity of 98.3% (171/174) and an efficiency of 93.3%
      (223/239) for influenza B. For nasal aspirates, RapidTesta FLU AB had a
      sensitivity of 83.2% (109/131), a specificity of 98.5% (135/137) and an
      efficiency of 91.0% (244/268) for influenza A as well as a sensitivity of 82.7%
      (43/52), a specificity of 97.7% (211/216) and an efficiency of 94.8% (254/268)
      for influenza B. RapidTesta FLU AB is characterized by high specificity, low
      false positive rate, and 10-minute detection of influenza virus. These advantages
      suggest that RapidTesta FLU AB is a useful kit to assist physicians in making a
      diagnosis of influenza on candidates for antiviral therapy.

PMID- 15508722
TI  - [Summary of questionnaires on leprosy in Yokohama City area and university
      hospitals].
AB  - We sent a questionnaire to members of Yokohama Medical Association and
      Departments of University Hospital to get an overview of leprosy patients in the
      clinic. Yokohama Medical Association: The rate of collection was approximately
      47%. Few doctors have taken medical care of Leprosy patients. Half of the doctors
      will take medical care, but they have little information about Leprosy. Aged
      doctors do not take medical care compared with young doctors. Departments of
      University Hospital: The rate of collection was approximately 74%. Doctors in the
      University Hospitals do not hesitate to take medical care of leprosy patients.
      Dermatologists actively take medical care and have a chance of getting
      information about leprosy. It is necessary to give doctors information about
      leprosy and its history of stigma.

PMID- 15508723
TI  - [Leprosy prevention and treatment in China].

PMID- 15508724
TI  - [Diaminodiphenylsulfone resistance of Mycobacterium leprae due to mutations in
      the dihydropteroate synthase gene].
AB  - The relation between diaminodiphenylsulfone (called dapsone)-resistance and point
      mutations of the dihydropteroate synthase (DHPS) gene was analyzed using dapsone
      resistant Mycobacterium leprae isolates derived from Japanese leprosy patients.
      The mutation was found at amino acid residues 53 or 55 of the DHPS. This finding
      suggests that two specific mutations in the DHPS gene involved in dapsone
      resistance of M. leprae.

PMID- 15508725
TI  - [Multi-drug resistant Mycobacterium leprae from patients with leprosy].
AB  - DNA sequences of Mycobacterium leprae in particular regions of the gyrA, rpoB,
      and folP genes responsible for resistance to new quinolones, rifampicin and
      dapsone, respectively, were analyzed. Among 88 isolates of M. leprae from leprosy
      patients in Japan, Haiti, Indonesia, Pakistan, and the Philippines, eleven
      isolates had mutational changes in 2 genes (resistance to 2 drugs), and 2
      isolates (Shinsei-1 and Zensho-4) showed mutations in 3 genes (resistance to 3
      drugs). These findings are suggesting emergence of multi-drug resistant M.
      leprae.

PMID- 15508727
TI  - [Human monocyte-derived multinucleated giant cells].
AB  - Multinucleated giant cells (MGC) are characteristic cells in granulomatous
      disorders such as sarcoidosis and leprosy. There are two types of MGC; foreign
      body-type and Langhans-type cells. The exact mechanisms of the formation and the
      functional significance of MGC are not determined, although their morphological
      features are well understood. MGC are also formed in vitro from peripheral blood
      mononuclear cells by stimulation with cytokines and lectins. Particularly IFN
      gamma is considered to play a pivotal role in monocyte fusion. IL-3, IL-4, IL-13,
      and GM-CSF are other reported cytokines involved in MGC formation. In addition to
      such inflammatory mediators, a factor derived from the pathogens of granulomatous
      disorders may be necessary for MGC formation. Muramyl dipeptide, a peptidoglycan
      portion of bacterial cell walls, is one of the candidates and can preferentially
      induce Langhans-type cells in in vitro MGC formation system. Although the exact
      mechanisms of in vitro MGC formation remains unknown, cell surface molecules such
      as P2X7 receptor, integrins, CD98, and macrophage fusion protein are considered
      to be involved in fusion process. Monocytes of sarcoidosis patients expressed
      higher levels of P2X7 and had a higher ability to induce MGC than those of
      healthy controls. Effective agents for sarcoidosis such as tranilast, alloprinol,
      and captopril inhibited in vitro MGC formation, suggesting their therapeutic
      effects through the direct effects on monocytes. Thus, an in vitro MGC formation
      model would be a useful tool to understand the relevance of MGC in granulomatous
      disorders.

PMID- 15508726
TI  - [New pharmacological availability of thalidomide based on experience in patients
      with multiple myeloma].
AB  - Thalidomide was developed in the 1950s as a sedative having only a low toxicity.
      However, McBride and Lenz reported in 1961 a close correlation between oral
      administration of thalidomide by pregnant women and a particular deformity
      (phocomelia) of their babies. In the 1990s, the biological activities of
      thalidomide were determined to include the control of tumor necrosis factor-alpha
      production and inhibition of angiogenesis. In 1994, Folkman et al. reported that
      thalidomide exhibited a strong inhibition of angiogenesis in their experiments
      with rabbits and that this effect had a significant relationship to phocomelia.
      They suggested a utility of thalidomide as a therapeutic agent for diseases that
      involve angiogenesis, particularly tumorous diseases. Furthermore, in 1994, Vacca
      et al. reported that the bone marrow of multiple myeloma (MM) patients was rich
      in blood vessels and that there is a causal relationship between the activity of
      MM and marrow angiogenesis. According to these data, thalidomide was tested in
      many countries as a new therapeutic agent for MM. In this review, new
      pharmacological availability of thalidomide is described on the basis of our
      experiences.

PMID- 15508728
TI  - [Functional changes of macrophages in Hansen's disease].
AB  - As an obligate intracellular pathogen, the principal host cells for Mycobacterium
      leprae are mononuclear phagocytes or macrophages. The macrophage is a primitive
      cell type being found in both early and advanced life forms, and possesses a
      variety of functions, such as phagocytosis of invaded bacteria, production of
      cytokines, antigen presentation and tumor killing. Hansen's disease is a chronic
      infectious disease characterized by specific host immune responses against M.
      leprae. In this article the macrophage is focused to dissect its functions in the
      disease.

PMID- 15508729
TI  - [Molecular pathogenesis of mycobacterial diseases].
AB  - Mycobacterial diseases, including tuberculosis, leprosy, and disease due to
      nontuberculous mycobacteria, are the major cause of death from infectious
      diseases around the world. About one-third of the world population is latently
      infected with Mycobacterium tuberculosis. Over 8 million new cases and nearly 2
      million deaths occur each year. Tuberculosis presents a significant health threat
      to the world. The pathogenicity of mycobacteria is related to their ability to
      escape killing by ingested macrophages, latent infection, and induce delayed type
      hypersensitivity. This has been attributed to several components of the
      mycobacterial cell wall, such as surface glycolipids, lipoarabinomannan,
      complement activation factor, heat-shock protein, and mycobacterial DNA binding
      protein. From the aspect of my research interests, I have focused on
      mycobacterial glycolipids and mycobacterial DNA binding protein in this article.
      Surface molecules of mycobacteria exert pleiotropic activities in both the
      microbe and host, and thus participate in the pathogenesis of mycobacterial
      diseases. The better understanding of mycobacterial pathogenicity may open the
      new avenue for the development of therapeutic and prophylactic interventions.

PMID- 15508730
TI  - [New international classification of headache].

PMID- 15508731
TI  - [Molecular biology and genetic study of migraine headache].

PMID- 15508732
TI  - [New trend of drug therapy for headache].

PMID- 15508733
TI  - [Topics of headache therapy: botulinum and blood patch].

PMID- 15508734
TI  - [Treatment of cerebral aneurysm: neurosurgical clipping versus endovascular
      coiling].

PMID- 15508735
TI  - [Preserved ability to read aloud kanji idioms in left handed alexia].
AB  - We report a 69-year-old left-handed man, who developed alexia after a right
      medial occipito-temporal lobe infarction. On admission to the rehabilitation
      department two months after the onset, neurological examination showed left
      hemianopia, left hemiparesis, decreased deep sensation on the left side, and
      alexia. A brain MRI demonstrated infarcts in the right medial occipito-temporal
      lobe and the splenium of the corpus callosum. Detailed neuropsychological
      examination was performed two months after the onset. The patient was alert and
      cooperative. His speech was fluent with some word-finding difficulty.
      Comprehension for spoken materials, repetition, and naming abilities were all
      preserved. Systematic examination for reading revealed that reading aloud was
      disturbed in both kanji and kana words. Reading comprehension was significantly
      better for kanji words than kana words. First, we examined the effects of number
      of characters in a word. The number of characters in a word didn't affect his
      reading performance. Second, his performance on reading aloud of usual kanji
      words was compared with that of kanji words representing idioms. A kanji idiom is
      different from usual kanji words, in which pronunciation of each character is
      selected from several options. Reading aloud kanji idioms was significantly
      better than usual kanji words. In addition, reaction time to complete reading a
      word was much shorter for kanji idioms than usual kanji. An analysis of
      qualitative features of errors revealed that most errors in kanji idiom reading
      were semantically similar to the correct answers, while many errors in usual
      kanji word reading were classified into "don't know" responses. These findings
      suggested that a kanji idiom was tightly connected to its pronunciation, which
      resulted in his much better performance for kanji idiom reading. Overlearning of
      a unique relationship between a kanji idiom and its pronunciation might modify
      neuronal organization for reading.

PMID- 15508736
TI  - [Selective volitional respiration control loss (inverse Ondiene's curse syndrome)
      in amyotrophic lateral sclerosis].
AB  - We investigated neuro-respiratory function of a 60-year-old woman with a 7-year
      history of amyotrophic lateral sclerosis. She was trachomized 4 years ago,
      however, spontaneous respiration had been observed. Plethysmography disclosed
      autonomous and abolished volitional control on breathing. Cough reflex and
      emotional laughing influenced on respiration pattern. Positive reaction of
      respiration to hypercapnia was observed. Then, it seemed to be preserved
      respiratory neurons in the medulla oblongata and bulbospinal tract, and
      remarkable impairement of the corticospinal tract.

PMID- 15508737
TI  - [Deep cerebral venous thrombosis: a report of three cases and review of the
      literature].
AB  - Three cases of cerebral deep venous thrombosis (CDVT) were reported with review
      of the literature. A 47-year-old female had taken estrogen-derived drug. The
      other two patients had no specific past history. On MRI, T2-weighted and fluid
      attenuated inversion recovery (FLAIR) images showed high signal intensity lesions
      at basal ganglia and thalamus. Diffusion-weighted image (DWI) detected only
      slightly high signal spots but apparent diffusion coefficient (ADC) images
      indicated mild increases of the ADC value. MR venogram and cerebral angiogram
      revealed obliteration of internal cerebral veins, great vein of Galen, and
      straight sinus. The two severely impaired patients received systemic
      heparinization, in which one patient preceded percutaneous transvenous
      angioplasty of straight sinus. One patient suffered cognitive disturbance and the
      other two patients fully recovered from their illness. The high signal intensity
      lesions on both T2-weighted image and FLAIR image disappeared and deep cerebral
      veins reappeared. The diagnosis of CDVT based on clinical symptoms is not simple
      but modern technology of MRI is very useful for diagnosis of CDVT. Once CDVT is
      detected, appropriate therapy should be started as soon as possible to avoid
      devastating outcome.

PMID- 15508738
TI  - [A case of cystic cavernous angioma accompanied by a fluid-fluid level on
      magnetic resonance imaging].
AB  - We describe the case of a patient with cavernous angioma (CA). A 44-year-old
      woman complained of numbness on the left side of the body as an initial symptom
      of the disease. The initial magnetic resonance (MR) imaging revealed a cystic
      mass with a fluid-fluid level without perifocal edema in the right thalamus on
      the T 2-weighted image (T 2WI) and T2*-weighted image (T2*WI). Her symptoms were
      self-controllable; therefore we decided to observe her natural course only with
      serial MR imaging. The cystic mass was not enhanced by gadolinium on T1-weighted
      images, although, we suspected the tumor was complicated by vascular
      malformation. Therefore, we performed cranial angiography to eliminate the
      possibility of bleeding from the vascular malformation. Angiography did not
      demonstrate tumor staining nor vascular malformation. Longitudinally, the tumor
      demonstrated mosaic signal intensities on each sequence with perifocal edema.
      Moreover, the tumor exhibited hypointensities on T2* WIs without perifocal edema.
      The natural history of the tumor on MR imaging exhibited a typical case of CA.
      Some previous reports described cystic CA with perifocal edema and vascular
      malformation. In our present case, we clinically diagnosed CA on the basis of the
      final MR imaging together with previous reports. An intra-axial fluid-fluid level
      is a very rare finding of MR imaging. Here, we report the case of a patient with
      cystic CA accompanied by a fluid-fluid level. This finding is not a pathognomonic
      sign of CA; although, we consider that it is very important to follow up
      carefully the natural history of such cases.

PMID- 15508739
TI  - [Bilateral chronic subdural hematoma in a young adult mimicking subarachnoid
      hemorrhage].
AB  - A 33-year-old man was admitted to our hospital with a sudden severe headache five
      days after the onset CT scan showed a slight high-density area in the basal
      cistern, mimicking subarachnoid hemorrhage (SAH), and diffuse brain swelling.
      However, conventional cerebral angiography and CT angiography failed to
      demonstrate aneurysms and vascular malformations. MRI showed bilateral subdural
      hematoma, but no SAH. Irrigation of liquefied subdural hematoma, causing high
      intracranial pressure, was carried out. Postoperative course was uneventful and
      his headache resolved within a day. The author presented a case of bilateral
      chronic subdural hematoma who presented with a sudden severe headache mimicking a
      SAH. Hyper attenuation in the basal cistern and subarachnoid space in CT, don't
      always indicate SAH. MRI, including fluid-attenuated inversion recovery (FLAIR)
      sequences, is useful in differentiating the "pseudo" SAH from "true" SAH, and
      lead to the right diagnosis.

PMID- 15508740
TI  - [Recurrence of bilateral spontaneous cervical internal carotid artery dissection
      after a 12-year-interval: a case report].
AB  - Recurrence of spontaneous cervical internal carotid artery (ICA) dissection is
      not rare (1%/year) but bilateral recurrence affecting the same cervical ICA is
      rare, especially after a 12-year-interval. A 41-year-old man exhibited left
      hemiparesis and angiography revealed tapered stenosis of his right cervical ICA.
      Within 2 days, his hemiparesis improved. After 21 days, repeated angiography
      showed complete resolution of the once-stenosed right cervical ICA. He was
      discharged with slight left hemiparesis. The follow-up angiography performed
      after 18 months disclosed not only the recanalization of the right cervical ICA
      but also a new concentric stenosis of his left cervical ICA. Since he presented
      no new neurological deficit, he was treated with an antiplatelet agent. The
      angiography performed 14 months later revealed normalization of bilateral
      cervical ICA. After 12 years, at the age of 53, he presented with worsening of
      his left motor weakness. Also on this occasion, angiography revealed bilateral
      cervical ICA dissection and their spontaneous resolution. The anamnesis revealed
      that he had experienced the same ischemic symptoms, that is, hemiparesis, aphasia
      and their spontaneous resolution, when he was 24 and 37 years of age. These 4
      episodes had some characteristics in common: occurrence in winter (from December
      to March), being preceded by moderate fever and upper respiratory tract
      infection. The pathogenesis of spontaneous cervical ICA dissection is unclear.
      From experience with this patient, we propose that the occurrence of spontaneous
      cervical ICA dissection might depend on a genetic predisposition and infection
      might play the role of a trigger.

PMID- 15508741
TI  - [Hemangioblastoma of the optic nerve growing like a dumbbell through the optic
      canal: case report].
AB  - We report a case of optic nerve hemangioblastoma in a 29-year-old man without a
      family history of von Hippel-Lindau disease or the other organ symptoms. He had
      progressive loss of vision and proptosis with a dull pain in his right eye.
      Magnetic resonance image (MRI) showed a gadolinium (Gd) enhancing solid tumor
      involving the prechiasmal right optic nerve with intraorbital extension. The
      tumor contained many signal voids of vessels and grew like a dumbbell through the
      right optic canal. Digital subtraction angiography demonstrated that the
      hypervascular tumor was fed by the ophthalmic artery and the orbital ramus of the
      middle meningeal artery. We succeeded in total resection of this hypervascular
      tumor by orbito-zygomatic approach. This tumor grew unusually like a dumbbell
      because it occurred in the optic nerve at the part of the optic canal.
      Histological examination revealed the tumor to be a characteristic
      hemangioblastoma. The postoperative course was uneventful. Supratentorial
      hemangioblastomas, especially optic nerve hemangioblastoma are extremely rare.
      This paper reviews the previous published cases and discusses their findings.

PMID- 15508742
TI  - [The cerebellopontine angle lipoma with unusual findings on T2-weighted image].

PMID- 15508743
TI  - [Multiplanar reconstruction (MPR) images of blow-out fracture].

PMID- 15508744
TI  - [Causative lesion of Claude's syndrome].

PMID- 15508745
TI  - Mouse tooth development time sequence determination for the ICR/Jcl strain.
AB  - To establish the normal dental development pattern of the ICR/Jcl strain of
      mouse, we analyzed a significant number of observations of the different
      developmental stages of the first mandibular molar, accurately recording the
      chronology of their daily embryonic development. Proliferation of the dental
      sheet began at day 12.5 in utero (E-12.5), the bud stage appeared at days E-13.5
      and E-14.5, the cap stage was observed at days E-14.5, E-15.5 and E-16.5 and the
      early bell stage at day E-17.5. The presence of predentin was observed at day E
      18.5 and dentin was observed 1 and 2 days after birth (D-1 and D-2). The late
      bell stage with presence of enamel was detected more than 3 days after birth.
      Embryonic and dental development in the ICR/Jcl strain of mouse is faster than in
      other well-known strains. The establishment of this developmental pattern will be
      useful for future investigations of transgenic mice.

PMID- 15508746
TI  - EDX fluorescence analysis and SEM observations of resin composites.
AB  - The purpose of this study was to evaluate the filler compositions of recently
      available light-cured resins. The composition of each resin paste was evaluated
      using an energy dispersive X-ray fluorescence spectrometer. Scanning electron
      microscopic observation of the polymerized resin pastes was also conducted. The
      main component of each resin composite was Si, while the other elements detected
      were Al, Ba, Sr, Zr, and K. These elementary compositions differed among the
      resin pastes used. Three different types of filler morphology were observed;
      splintered, prepolymerized and splintered, and spherical. The results of this
      study have thus characterized recently developed resin composites based on their
      filler elements and morphology.

PMID- 15508747
TI  - Intra-familial distribution of nine putative periodontopathogens in dental plaque
      samples analyzed by PCR.
AB  - It is of great importance to understand the distribution of periodontopathogens
      within family members when considering the risk of periodontitis in children. The
      purpose of this study was to investigate the distribution of periodontopathogens
      among family members. We used the polymerase chain reaction method to test 4,8,
      and 7 probands with healthy gingiva, gingivitis, and periodontitis, respectively,
      and their 60 immediate family members. Plaque samples were collected from all
      erupted teeth sites using a sterile toothbrush. In 161 of the 165 positive cases,
      if a child harbored one of the periodontopathogens then at least one of the
      parents was also positive for the same bacterium. The prevalence of parent-child
      co-infection was 42.9% for Actinobacillus actinomycetemcomitans, 21.4% for
      Porphyromonas gingivalis, 29.2% for Treponema denticola, 59.5% for Tannerella
      forsythensis (Bacteroides forsythus) and 16.7% for Prevotella intermedia. Our
      results indicate that parents could be an important source of periodontopathogens
      for the colonization that occurs in their children.

PMID- 15508748
TI  - Rate of cultivable subgingival periodontopathogenic bacteria in chronic
      periodontitis.
AB  - Although microbiological studies have identified more than 400 bacterial species
      in periodontal pockets, only a limited number have been implicated as periodontal
      pathogens. The purpose of this study was to investigate the incidence of
      cultivable subgingival periodontopathogenic bacteria in chronic periodontitis.
      Bacterial samples were collected with sterile paper points from the deepest
      periodontal pockets ((5 mm) of 203 patients: 92 males and 111 females, aged 35-55
      years. The samples were cultured under anaerobic and capnophilic conditions using
      selective and non-selective media. Isolates were characterized to species level
      by conventional biochemical tests and a commercial rapid test system. The
      isolates were Actinobacillus actinomycetemcomitans (26.8%), Porphyromonas
      gingivalis (21.9%), Capnocytophaga sputigena (16.7%), Eikenella corrodens
      (13.2%), Prevotella intermedia (10.5 %), Prevotella disiens (3.1%),
      Peptostreptococcus micros (2.9%), Capnocytophaga gingivalis (2.2%), Prevotella
      corporis (1.8%), Peptostreptococcus magnus (1.3%) and Fusobacterium nucleatum
      (0.4%). No periodontopathogenic bacterial growth was observed in 14 of the
      samples (6.2%). The number of samples associated with monobacterial growth and
      polybacterial growth were 74.9% and 18.2% respectively. It is concluded that the
      bacterial composition associated with a number of patients' samples is quite
      complex, and that some of cultivable anaerobic and capnophilic bacteria act as
      periodontal pathogens in chronic periodontitis.

PMID- 15508749
TI  - Subcloning of the 200-kDa Porphyromonas gingivalis antigen gene and inhibition of
      hemagglutination by an antibody against the recombinant protein.
AB  - Porphyromonas gingivalis is a major etiologic agent of periodontitis and exhibits
      hemagglutinating and adherence activities. We previously succeeded in molecular
      cloning the 200-kDa cell-surface antigenic protein (200-k AP), designated pMD101,
      that is recognized in sera from periodontitis patients, and identified the 200-k
      AP as a hemagglutinin A (HagA) derivative. HagA is one of the hemagglutinins
      known to be a useful vaccine against periodontitis. HagA has four large,
      contiguous, direct repeats and the repeat unit is believed to contain the
      hemagglutinin domain. Because production of 200-k AP was low in the Escherichia
      coli host, it was difficult to obtain large amounts of recombinant protein. In
      this study, we attempt to subclone the gene encoding the useful antigen from
      pMD101 in an effort to obtain large quantities. A subclone, designated pMD160,
      encoding a fusion protein of 80-kDa HagA and maltose-binding protein was
      successfully constructed, and the novel clone produced relatively large amounts
      of recombinant protein. DNA nucleotide sequences of the pMD160 insert
      demonstrated that the 80-kDa protein contained a short hemagglutinin motif and a
      direct repeat unit region. The recombinant protein was purified to homogeneity
      and rabbit antiserum was raised. The antibody was capable of inhibiting the
      hemagglutinating activity of P. gingivalis. These findings suggest that novel 80
      kDa HagA derivative proteins can be produced efficiently from E. coli hosts and
      these may be useful in developing immunotherapy against periodontitis infected by
      P. gingivalis.

PMID- 15508750
TI  - Telomeres on chromosome 21 and aging in lymphocytes and gingival fibroblasts from
      individuals with Down syndrome.
AB  - Progressive chromosome 21 loss in individuals with trisomy 21 or Down syndrome
      (DS) is supposedly related to their premature senescence. In addition, the
      telomere hypothesis of cellular aging involving telomere shortening in normal and
      accelerated aging in vivo and in vitro is well documented. This study
      investigated the integrity of two chromosome 21 regions (the 21q telomere and the
      21q22.13-q22.2 region) and their relationship with aging by means of fluorescence
      in situ hybridization (FISH) in lymphocytes and gingival fibroblasts cells. The
      use of tissues from different germ layers allows detection of mosaicism.
      Chromosome variations in tissue from the neuroectoderm layer could explain the
      variable phenotype of DS. This approach is original in the literature. Lymphocyte
      and gingival fibroblast nuclei from 18 affected individuals aged 5-54 years were
      analyzed. Although not significant (P = 0.06), analysis from 11 tissue-matched
      individuals as well as the comparison between lymphocytes and fibroblasts from
      different subjects (P = 0.05) suggested that lymphocyte cells are more likely to
      miss 21q telomere signals. Hence, gingival fibroblasts are probably capable of
      more efficient cell repair, and the occurrence of mosaicism is more related to
      cell proliferation than to germ layer origin. Investigation of the 21q22.13-q22.2
      region from six tissue-matched individuals and from different DS patients
      revealed no significant differences between the tissues.

PMID- 15508751
TI  - Feasibility of eradication of mutans streptococci from oral cavities.
AB  - OBJECTIVES: Dental caries prevention programs using chlorhexidine (CHX) have been
      proposed, but CHX's effect in reducing levels of mutans streptococci (S. mutans
      and S. sobrinus) appears to last for only a few months. The aim of this study was
      to attempt to eradicate mutans streptococci from the oral cavity using intensive
      professional mechanical tooth cleaning (PMTC) and topical application of CHX in
      custom-made trays. METHODS: Seven adult dentate subjects participated in this
      study (mean age 53.7+/-5.6, age range 46 to 62, mean DMFT, 9.1+/-4.2). For each
      subject, PMTC was carried out eight times within ten days. After each PMTC, 1%
      CHX was applied twice to the tooth surface using custom-made trays. In addition,
      as home treatment, subjects were required to carry out tooth brushing three times
      a day, and apply 0.2% CHX in custom trays after brushing in the morning and
      evening. In addition, subjects rinsed with 0.2% CHX solution after lunch.
      Salivary levels of mutans streptococci were evaluated using Dentocult-SM at
      baseline and on days 9, 20, 70, 120. RESULTS: Mutans streptococci were eradicated
      by day 120 from 4 of the 7 seven subjects participating in this study. Those 3
      subjects still harboring mutans streptococci exhibited deep periodontal
      pocketing. CONCLUSIONS: Eradication of mutans streptococci from the oral cavity
      is feasible using a combination of CHX application in custom-made trays and
      intensive PMTC.

PMID- 15508752
TI  - Influence of adhesive polymerization mode on dentin bond strength of direct core
      foundation systems.
AB  - This study examined the influence of various adhesive systems on dentin bond
      strength of direct core foundation resins. Two commercially available direct core
      foundation resin systems and 2 adhesive polymerization modes were used. Facial
      bovine dentin surfaces were wet ground on 600-grit SiC paper. Dentin surfaces
      were treated according to the manufacturers' instructions and were light
      polymerized (control). Chemical- and light-polymerized adhesive systems were used
      separately. The resin paste was condensed into a mold and bonded to the dentin
      surface. Ten specimens per test group were stored in water at 37 degrees C for 24
      hours, and a shear test was conducted at a crosshead speed of 1.0 mm/minute using
      a universal testing machine. Analysis of variance (ANOVA) and Duncan's multiple
      comparison test were performed (alpha = 0.05). Dual polymerization of resin
      pastes revealed higher bond strength with the combination of light-polymerized
      adhesive (22.8-24.3 MPa), but significantly lower bond strength with the
      combination of a chemical-polymerized adhesive (4.2-5.7 MPa). The present data
      suggests that dentin bond strengths in direct core foundation systems can be
      influenced by the combination of adhesive and resin paste.

PMID- 15508753
TI  - Differences in self-reported oral health behavior between dental students and
      dental technology/dental hygiene students in Jordan.
AB  - The aim of this study was to compare differences in oral health behavior between
      dental students and dental technology/dental hygiene students in Jordan. One
      hundred and five dental students and seventy-eight dental technology/dental
      hygiene students were recruited into this study. All subjects were recruited from
      the students who were receiving training at the clinics and laboratories that
      belong to the Faculty of Dentistry, Jordan University of Science and Technology.
      The Hiroshima University-Dental Behavioral Inventory (HU-DBI) was used to assess
      the oral heath behavior of the subjects. Significant differences were found
      between students from different disciplines. Dental students were found to worry
      more about visiting their dentist, to be less aware of bleeding gums when
      brushing and were less bothered by the color of their gums compared with dental
      technology and dental hygiene (DT/DH) students (P < 0.05, P < 0.001 and P < 0.05,
      respectively). Dental students tended to be more professionally educated about
      brushing and to have a belief that they cannot clean their teeth well without
      using toothpaste (P < 0.01 and P < 0.001, respectively). Most of them did not
      feel they have brushed well unless they brush with strong strokes (P < 0.05). A
      logistic regression model showed that it might be possible to distinguish dental
      students from DT/DH students by using three items of the HU-DBI and the level of
      dental education. The difference in the HU-DBI scores was not a major feature.
      There were significant differences in oral health attitudes/behavior between
      dental students and DT/DH students. The findings might reflect differences in
      students' training experience and education between different specialties.

PMID- 15508754
TI  - Granulomatous glossitis: a case report.
AB  - A 50-year-old man was admitted to our clinic with a complaint of lingual
      enlargement. Detection of non-caseous epithelioid granuloma on histopathological
      examination led to a diagnosis of a granulomatous glossitis. Extensive
      investigation for the presence of associated disorders yielded negative results.
      Metranidazole and clofazimine were totally ineffective and tetracycline led to a
      minimal improvement. No associated disorder was detected at a 4-year follow-up
      examination. The position of granulomatous glossitis within the spectrum of
      orofacial granulomatous conditions is discussed.

PMID- 15508755
TI  - [Symptoms preceding psychosis].

PMID- 15508756
TI  - [Interaction of genes and environment].

PMID- 15508757
TI  - [Genes behind humanity, rage, peace and the brain of apes].

PMID- 15508758
TI  - [Nitric oxide in the acute care of newborns and premature infants].

PMID- 15508759
TI  - [Lymphomas of the gastrointestinal tract].

PMID- 15508760
TI  - [Attachment theory from research findings to practice and treatment].

PMID- 15508761
TI  - [Diversity of systemic connective tissue disorders].

PMID- 15508762
TI  - [Drug allergy syndromes in adults, what is the right time to test for
      hypersensitivity?].

PMID- 15508763
TI  - [Rapid development of dementia of an elderly person, diagnosis and successful
      treatment].

PMID- 15508764
TI  - [Stiff person syndrome].

PMID- 15508765
TI  - [Sudden malfunction of a finger].

PMID- 15508766
TI  - [Extrauterine pregnancy].

PMID- 15508767
TI  - [Arteriosclerosis, Barker's hypothesis, homocysteine and bandworm].

PMID- 15508770
TI  - Nursing practice update: answers to questions recently/frequently asked by NJ
      APNS.

PMID- 15508771
TI  - Research dissemination and utilization.
AB  - Why does sun protection and skin cancer awareness need to be addressed? Skin
      cancer is the most common form of cancer. There has been a steady increase in the
      incidence of melanoma every year. Evidence shows that ultraviolet radiation from
      sun exposure during early life is associated with an increased risk of skin
      cancer in later life. The majority of skin cancer can be prevented by limiting
      sun exposure. Children and adolescents spend more time exposed to the sun than
      adults. What are the obstacles to skin cancer prevention? Public perception of
      tanning needs to be changed. The public associates well being with a tan. The
      public is uneducated on skin cancer prevention. Skin cancer awareness does not
      take precedence in our society. School health providers are not active in
      stressing the importance of avoiding sun exposure. How can nurses promote sun
      protection? Become educated in the identification of atypical lesions. Reinforce
      the benefits of sun protection. Recommend sun protection techniques to clients at
      every office visit. Partner with parents in stressing to children the importance
      of skin protection. For more information contact. The American Academy of
      Dermatology (www.aad.org). The American Medical Association. The Centers for
      Disease Control and Prevention.

PMID- 15508773
TI  - Malaria at the turn from the 2nd to the 3rd millenium.
AB  - With an annual incidence of 300-500 million clinically manifest cases and a death
      toll of 1.1-2.7 million, malaria is still one of the most important communicable
      diseases. Currently about 40% of the world's population live in areas where
      malaria is endemic, as against 80% in 1950. Although this reflects considerable
      impact of intensive malaria control, especially between 1950 and 1970, the
      disease continues to affect large populations in all parts of the tropics and
      subtropics, and remains most deeply rooted in tropical Africa, the region with
      90% of the global malaria incidence. As malaria in tropical Africa is
      predominantly caused by Plasmodium falciparum, this area also suffers from the
      highest specific mortality. Drug resistance of P. falciparum is the most
      formidable obstacle in the fight against the disease since it jeopardizes the
      most elementary objective of malaria control, namely the elimination of mortality
      and the reduction of suffering from malaria.

PMID- 15508774
TI  - [Treatment of Acanthamoeba keratitis: possibilities, problems, and new
      approaches].
AB  - Acanthamoeba keratitis is a corneal disease associated predominantly with contact
      lens wear. The occurrence of Acanthamoeba keratitis has been rising since 1990 in
      correlation to the growing number of contact lens wearers. To date approximately
      2000 cases have been published around the world. Due to the complicated
      diagnostics, the elaborate treatment and the usually bad compliance of the
      patients, Acanthamoeba keratitis unfortunately very often takes a serious
      progression, which may lead to serious visual loss and perforating keratoplasty.
      Today, local treatment with a combination of polyhexamethylene biguanide (PHMB)
      and propamidine isethionate (Brolene) is considered the first line therapy for
      Acanthamoeba keratitis. Alternatively also a combination of propamidine and
      chlorhexidine or neomycine achieves good therapeutic results. However, the
      complicated mode of application consistently remains a problem. The intensive
      local treatment, i.e. hourly application of therapeutics during the first three
      days day and night makes hospitalization inevitable. Moreover, sufficient
      efficacy can not always be achieved, and also resistance against propamidine has
      already been observed. Recently propamidine has sometimes been replaced by
      hexamidine, which seems to have a greater cysticidal activity. A new path might
      be struck by the application of alkylphosphocholines. These are phosphocholines
      esterified to aliphatic alcohols. They exhibit in vitro and in vivo
      antineoplastic activity and have been shown to be cytotoxic against Leishmania
      donovani, Trypanosoma cruzi, and Entamoeba histolytica. A recent study has
      demonstrated that particularly hexadecylphosphocholine is highly effective also
      against various strains of Acanthamoeba.

PMID- 15508775
TI  - [The confusing diversity of IgM tests in the diagnosis of Toxoplasma infections:
      efforts towards an optimal strategy].
AB  - IgM antibodies are indicative for a recent infection, thus the detection of this
      isotype is of essential significance particularly in the diagnosis of infections
      with Toxoplasma gondii during pregnancy (primary infection, seroconversion).
      Numerous serological tests and test kits (e.g. indirect immunofluorescent
      assay/IFAT, enzyme-linked immunosorbent assay/ELISA, Immunosorbent agglutination
      assay/ISAGA, Westernblot/WB) using different antigens and antigen preparations
      are provided by numerous companies. The sensitivities of such tests, however,
      variy considerably: The serological test results of four pregnant women with
      seroconversions and of three newborns from mothers with seroconversions are
      presented: VIDAS M and ISAGA M from one company yielded false negative results in
      three pregnant women whereas ISAGA M from another company could detect specific
      IgM. However, examination of the cord blood of the three newborns unanimously
      revealed IgM-negative results. Thus, our diagnostic strategy for pregnant women
      includes IIFT (or SFT) as basic test and ISAGA M (Toxotool I from Innogenetics)
      as well as IgG avidity test as additional tests; the serological diagnosis of
      suspected congenital infection comprises IFAT (or SFT), ISAGA M (from
      Innogenetics) and IgM/IgG Westernblot.

PMID- 15508776
TI  - Malaria drug-susceptibility testing. HRP2-based assays: current data, future
      perspectives.
AB  - In past decades, malaria in-vitro drug-susceptibility assays have become an
      indispensable tool for the development of novel drugs, as well as for the
      surveillance of antimalarial drug resistance. The traditional in-vitro assays,
      however, remain tedious procedures, which, depending on the method employed,
      require a high degree of expertise, sophisticated laboratory infra-structure,
      skills and patience. We therefore developed a new drug sensitivity assay for
      Plasmodium falciparum based on the measurement of histidine-rich protein II
      (HRP2), a histidine and alanine-rich protein produced by P. falciparum. The assay
      uses a simple HRP2 double-site sandwich ELISA to quantify parasite growth and its
      inhibition. The complete ELISA takes about 2-3 hours to perform and requires
      little technical equipment. In our experiments with laboratory strains of P.
      falciparum against common antimalarials, the results closely parallel those
      obtained from the isotope assay and from WHO schizont maturation tests (P <
      0.001). Preliminary results using the HRP2 assay in our field studies in 2002
      suggest similar outcomes. In this setting the high sensitivity and simplicity of
      the assay is of particular advantage. The data closely parallel those obtained
      with the traditional WHO assay (Mean difference on the log scale: 0.033; R =
      0.942; P < 0.001). The assay is currently being further validated under field
      conditions. It has proved to be a valuable tool for a wide range of applications,
      from epidemiological field studies to the screening of new drugs, and may
      therefore have the potential to replace traditional in-vitro drug-sensitivity
      techniques.

PMID- 15508777
TI  - In-vitro interaction of tafenoquine and chloroquine in Plasmodium falciparum from
      northwestern Thailand.
AB  - The blood schizontocidal, pharmacodynamic interaction between tafenoquine (WR
      238605--a 5-phenoxyprimaquine derivative--and chloroquine was investigated, using
      an in-vitro test for the inhibition of schizont maturation, in 15 fresh isolates
      of Plasmodium falciparum that originated from northwestern Thailand and
      neighbouring Myanmar. In this area the parasite is highly resistant to
      chloroquine. The geometric mean cut-off concentrations of schizont maturation for
      tafenoquine and chloroquine were 5261 nM and 7638 nM, respectively. With a
      mixture of tafenoquine and chloroquine, the mean cut-off concentration was 5252
      nM, corresponding to 389 nM tafenoquine + 4863 nM chloroquine. Further analysis
      showed that the interaction between tafenoquine and chloroquine was additive
      within the range of EC20 and EC77. At concentrations higher than the EC77,
      interaction was moderately synergistic. While tafenoquine did not reverse the
      resistance to chloroquine to the degree of clinically relevant sensitivity, there
      was evidence that the blood schizontocidal efficacy of tafenoquine would be
      enhanced in the presence of chloroquine.

PMID- 15508778
TI  - Comparison of the in-vitro activity of amodiaquine and its main metabolite,
      monodesethyl-amodiaquine, in Plasmodium falciparum.
AB  - After its rehabilitation for therapeutic use in uncomplicated falciparum malaria,
      there is renewed interest in amodiaquine. After oral administration, the drug
      undergoes rapid metabolism to monodesethyl-amodiaquine, and in patients with
      normal hepatic function the parent drug usually becomes undetectable within a few
      hours. The main antimalarial activity is therefore mainly due to the metabolite.
      In a comparative study in northwestern Thailand, 21 fresh isolates of Plasmodium
      falciparum were tested, in parallel, for their in-vitro sensitivity to both
      compounds, using the WHO micro-test Mark II, measuring the inhibition of schizont
      maturation. The geometric mean cut-off concentrations of schizont maturation were
      1826 nM (related to blood) for amodiaquine, and 1654 nM for monodesethyl
      amodiaquine. The log-probit regressions for both compounds showed good fits to
      the data points. The EC50 values were 331 nM and 291 nM, and the EC90 values 1337
      nM and 993 nM for amodiaquine and monodesethyl-amodiaquine, respectively.
      Differences between regression slopes and effective concentrations were well
      below statistical significance. Both compounds showed highly significant activity
      correlation. These findings suggest that the sensitivity of Plasmodium falciparum
      to amodiaquine closely reflects its sensitivity to monodesethyl-amodiaquine.

PMID- 15508779
TI  - In-vitro response of Plasmodium falciparum to the main alkaloids of Cinchona in
      northwestern Thailand.
AB  - The blood schizontocidal activity of the four main Cinchona alkaloids against
      Plasmodium falciparum was compared in 46 fresh parasite isolates, using an in
      vitro test measuring the drug-specific inhibition of schizont maturation. The
      studies were conducted in June-August 2001 at Mae Sot, northwestern Thailand, an
      area where quinine alone is no longer able to eliminate infections with P.
      falciparum. Quinidine showed the highest blood schizontocidal activity, followed
      by cinchonine, cinchonidine and finally quinine, which was identified as the
      least active compound. The isolates showed marked heterogeneity in their response
      to the Cinchona alkaloids. There was also high correlation of activity among all
      four alkaloids. The mean EC50 values for quinine, quinidine, cinchonine and
      cinchonidine were 144 nM, 80 nM, 104 nM and 225 nM, respectively, and the EC99
      values 8040 nM, 861 nM, 1176 nM and 6531 nM. The EC99 values for quinine and
      cinchonidine are beyond the therapeutic concentration range and those for
      quinidine within it. For cinchonine, values are likely to be within this range,
      but toxicological and pharmacokinetic studies on this compound are required for
      clarifying its potential future role in the treatment of falciparum malaria.

PMID- 15508780
TI  - Clinical and parasitological response of Plasmodium falciparum to chloroquine and
      sulfadoxine/pyrimethamine in rural Uganda.
AB  - Following the WHO protocol for in-vivo tests in areas with intense transmission
      of uncomplicated falciparum malaria, a randomized comparison of the invivo
      efficacy of chloroquine alone, sulfadoxine/pyrimethamine alone, and their
      combined administration was carried out in the third quarter of 2001 in
      Kaberamaido District, northeastern Uganda. Malaria in the study area is hyper
      endemic, with a high prevalence of Plasmodium falciparum. The patients were
      infants and young children with a median age of 15 months. Of the 117 originally
      enrolled patients, 104 had a complete follow-up with presentation at all
      scheduled examinations. In the chloroquine group (n = 42), 55% were classified as
      adequate clinical response, 26% as early treatment failure, and 19% as late
      clinical failure. In the sulfadoxine/pyrimethamine group (n = 30), the respective
      figures were 83%, 13% and 3%, and in the group with combined treatment (n = 32),
      88%, 6% and 6%. In terms of clinical cure rate, speed of clinical relief and
      parasite clearance the combined treatment proved to be the most effective of the
      three drug regimens. In the patients with adequate clinical response, a
      significant post-therapeutic increase of the haematocrit was observed, which was
      particularly marked in patients who had also cleared their parasitaemia. Increase
      of the efficacy of chloroquine with age indicates the early development of semi
      immunity in the study area, with conserved efficacy of chloroquine in semi-immune
      persons.

PMID- 15508781
TI  - In-vitro sensitivity testing of Plasmodium vivax: response to lumefantrine and
      chloroquine in northwestern Thailand.
AB  - The acquisition of resistance to chloroquine by Plasmodium vivax in parts of the
      Australasian and Malaysian epidemiological zones and hitherto unconfirmed reports
      of such resistance in neighbouring zones show the need for monitoring the drug
      response of P. vivax. In this study, a recently developed in-vitro micro
      technique for the assessment of the parasite's sensitivity to chloroquine was
      adapted to and validated for lumefantrine. In 21 P. vivax isolates tested at Mae
      Hong Son, northwestern Thailand, in 2001, the mean geometric cut-off
      concentration for full inhibition for lumefantrine was 2080 nM. The EC50 and EC90
      were 12 nM and 237 nM, respectively. The response was well within the putative
      therapeutic range. Sensitivity to chloroquine was assessed in 18 P. vivax
      isolates, showing a geometric mean cut-off concentration of 1095 nM and a wider
      variation of the individual cut-off points compared with lumefantrine. The EC50
      and EC90 for chloroquine were 16 nM and 511 nM, respectively. One of the
      isolates, from Myanmar, showed low sensitivity to chloroquine.

PMID- 15508782
TI  - [Must we expect an epidemic of measles in the near future in Southern Tyrol?].
AB  - Measles, Mumps and Rubella (MMR) vaccination is recommended in Italy. A country
      wide study of the 1996 birth cohort revealed that coverage with MMR vaccine in
      the autonomous Province of Bolzano is the third lowest in Italy (after Campania
      and Calabria). The aim of the study was to evaluate the situation regarding
      measles in order to plan and implement necessary strategies. To assess MMR
      vaccine coverage, routine vaccination data were evaluated for quality and
      validity, and subsequently MMR coverage rates were calculated by birth cohort
      (1996-99) and commune. In addition, a descriptive epidemiologic analysis of all
      reported measles cases was performed. Hospital discharge records were used to
      estimate the complications and costs of hospital admitted measles cases. MMR
      vaccine coverage rates vary between rural (40%) and urban (80%) areas.
      Furthermore, communes with more than 50% Italian speaking inhabitants have higher
      MMR vaccine coverage than communes mainly populated by German speaking persons.
      In 1997 and 1999, epidemics with 1,889 and 992 cases, respectively, were
      reported. Five- to nine-year-old children were the most affected age group. Most
      cases were reported from communes with vaccine coverage rates below 40%. Six
      percent of measles cases, reported between January 1996 and October 2001 were
      admitted to hospital. The mean period of admission for measles cases was 4.6 days
      (range 1 to 84 days), the mean estimated costs 1,987.18 Euro per patient. The
      total amount of direct costs was estimated to be 386,437.72 Euros. Due to low
      vaccine coverage rates, especially in rural areas, and the ongoing circulation of
      the measles virus in the population, it is likely that an extensive measles
      epidemic will occur in the near future, resulting in evitable suffering of
      patients and extensive costs for the public health system. Only an effective
      immunization campaign will be able to prevent a future epidemic.

PMID- 15508783
TI  - [Sero-epidemiological studies of zoonotic infections in hunters--comparative
      analysis with veterinarians, farmers, and abattoir workers].
AB  - The aim of this study was to investigate seroprevalences to zoonotic pathogens in
      hunters, to compare the results with other predisposed occupational groups
      already investigated and to propose preventive measures. Blood samples were taken
      from 146 male and 3 female hunters from the provinces of Styria and Burgenland in
      the south-east of Austria and anamnestic data were obtained using a
      questionnaire. The serological investigations included the following bacterial,
      viral and parasitic zoonotic agents or zoonoses, respectively (antibody
      prevalence rates in brackets): borreliosis (IgG 42%, IgM 7%), brucellosis (1%),
      chlamydiosis (3%), ehrlichiosis (IgG 15%, IgM 3%), leptospirosis (10%),
      tularaemia (3%), Q fever (0%), encephalomyocarditis virus (EMCV, 15%), Puumala
      Hantavirus (10%), Newcastle Disease virus (4%), Echinococcus multilocularis/E.
      granulosus (5%/11%), toxocariasis (17%). Particularly striking in comparison with
      the control group and the veterinarians, farmers and slaughterhouse workers
      examined in earlier projects were the high seroprevalences to Borrelia
      burgdorferi sensu lato, Ehrlichia spp., Leptospira interrogans, E. granulosus and
      E. multilocularis, encephalomyocarditis, Puumala-Hantavirus and Newcastle Disease
      virus as well as to Brucella abortus and Francisella tularensis. The present
      study indicates that hunters are especially exposed to zoonotic pathogens.

PMID- 15508784
TI  - Hygienic evaluation of terraria inhabited by amphibians and reptiles:
      cryptosporidia, free-living amebas, salmonella.
AB  - Amphibians and reptiles are popular pet animals in about 90.000 Austrian
      households despite their frequently debated capacity to transmit diseases
      associated with animal keeping. We studied the epidemiological significance of
      the triangle animal keeper, exotic pet animal, and feed mice by investigating the
      frequency of three intestinal infestations, caused by cryptosporidia,
      opportunistic free-living amebas and salmonella, in amphibians and reptiles
      living in a public vivarium. In addition to recording the first known occurrence
      of Naegleria australiensis in Austria, and of this species and of Acanthamoeba
      polyphaga in the feces of reptiles worldwide, we also detected a strong
      association between Salmonella subspecies I and captive reptiles and between S.
      sub-species III and free-living lizards. Thus, animal keeper, the exotic animals
      kept, and the feed mice may constitute an epidemiological pool for the
      interchange of these infectious agents. This new epidemiological situation may
      cause an increase of some opportunistic and exotic diseases such as reptile-borne
      salmonellosis. Despite the perceived benefits of keeping exotic animals in a
      household, the general public and especially those who have an immunodeficiency
      must be made aware of the danger of infectious diseases possibly being spread by
      their pets.

PMID- 15508785
TI  - [Multibacillary leprosy in Tyrol].
AB  - Five cases of multibacillary leprosy have been diagnosed in a period of 15 years
      (1987-2001) at the outpatient Department of Neurology of the University Hospital
      Innsbruck. All patients presented with dermatological and mild to severe
      polyneuropathic signs and symptoms. 4/5 patients recovered fully, whereas 1
      patient with an initially severe polyneuropathy showed persistent polyneuropathy
      as long-term sequela. The prevalence of leprosy in the catchment area of the
      Department of Neurology, University Hospital Innsbruck (comprising the entire
      province of Tyrol--650,000 inhabitants) is to be calculated as 0.5/1 million. The
      incidence of newly diagnosed leprosy within this province of Tyrol is
      0.04/100,000/year. The aim of the presentation of these 5 patients is--beside the
      epidemiologic aspect--to alert all neurologists and dermatologists that this
      disease still exists--despite decreasing prevalence and incidence rates on a
      global scale; this is of particular importance since neurological long-term
      sequelae can only be avoided by early diagnosis.

PMID- 15508786
TI  - [Ophthalmomyiasis caused by Oestrus ovis in a 3 year old boy].
AB  - Oestrus ovis larvae are obligatory parasites of the nasal and sinus cavities of
      sheep and goats. Oestrosis in small ruminants is prevalent in Mediterranean and
      tropical countries. Occasionally, humans are affected by ocular myiasis
      (ophthalmomyiasis) and more rarely, nasal myiasis. A case of human
      ophthalmomyiasis caused by first instar larvae of Oestrus ovis in a 3 year old
      boy was observed in Gran Canaria. Acute catarrhal conjunctivitis developed within
      few hours. During the inspection of the eye several larvae could be observed,
      moving quickly over the cornea to the conjunctival sac. Rinsing and mechanical
      removal of the larvae lead to an uncomplicated recovery.

PMID- 15508787
TI  - [Diagnostic usefulness of selected tumor markers (CA125, CEA, CYFRA 21-1) in
      bronchoalveolar lavage fluid in patients with non-small cell lung cancer].
AB  - Numerous studies have been performed to determine diagnostic or prognostic
      utility of tumor markers in patients with lung cancer. The aim of the study was
      to evaluate the diagnostic usefulness of the tumor markers CA 125, CEA and CYFRA
      21-1 in bronchoalveolar lavage fluid (BALF) in patients with non-small cell lung
      cancer (NSCLC). BAL was performed in 13 patients with NSCLC during diagnostic
      bronchofibroscopy. The control group consisted of 12 patients with sarcoidosis
      and 13 healthy volunteers. Tumor markers were determined in BALF supernatants
      using electrochemiluminescence technique (Elecsys 1010, Roche). To determine
      optimal cut-off values of tumor markers in BALF ROC curve was used. CEA and CA
      125 concentration in BALF were significantly higher in NSCLC patients than in
      healthy volunteers and patients with sarcoidosis. CYFRA 21-1 in BALF was higher
      in NSCLC patients than in healthy volunteers, but no significant difference was
      found between NSCLC and sarcoidosis patients. The cut-off values of BALF
      concentration of CA 125, CEA and CYFRA 21-1 were 95 IU/mL, 3 ng/ml and 3 ng/ml,
      respectively. The sensitivity and specificity of CEA and CA 125 in BALF were
      100%, 84% and 92%, 80%, respectively. In conclusion, we suggest that among the
      chosen markers, determination of CEA in BALF is the most useful in diagnosis of
      NSCLC. It may be a complementary method in diagnosing of patients in whom tumor
      cannot be visualized by bronchofibroscopy. These results need confirmation in
      larger groups of patients.

PMID- 15508788
TI  - [Inhibition of adenosine deaminase activity by drugs influencing the
      cardiovascular system].
AB  - Adenosine deaminase (ADA) is an unique enzyme which catalyzes conversion of
      adenosine and 2'-deoxyadenosine to inosine and 2'-deoxyinosine respectively. One
      of physiological roles of this enzyme is modulation of its substrate--adenosine
      concentration (both intracellular and extraectocellular). In presented work the
      influence of acetylsalicylic acid, metoprolol, simvastatin, isosorbide
      mononitrate and molsidomine on total activity of adenosine deaminase and its
      isoenzymes--ADA1 and ADA2 in vivo was studied. We have affirmed that simvastatin
      decreased of tADA activity by 50%, acetylsalicylic acid by 34%, metoprolol by
      29.1% and isosorbide mononitrate by 19.3%. Only after molsidomine administration
      were no significant changes in ADA activity observed. The result showed that the
      decline of ADA activity was mainly due to marked decrease in ADA2 isoenzyme.

PMID- 15508789
TI  - [Change in biomarkers of osteoporosis in rheumatoid arthritis patients treated
      with infliximab].
AB  - A study was made to evaluate bone turn-over in rheumatoid arthritis (RA) patients
      treated with infliximab. Twenty-two patients with established RA were included.
      In all patients, biochemical markers of osteoporosis: osteocalcin (BGP), alkaline
      phosphatase (bone isoenzyme), deoxypyridinoline (Dpd), acute phase proteins (CRP,
      AGP, ACT, AGP-RC), and interleukin 6 (IL-6) were determined before treatment, at
      week 30, and at week 46. Two markers (BGP, Dpd) were significantly decreased at
      both weeks 30 and 46. Moreover, a fall in serum levels of acute phase proteins
      and IL-6 was seen. The results suggest that anti-TNF treatment with infliximab
      not only decreases activity of inflammation but also may slow down bone turn
      over. Further research is needed to assess its potential in reducing risk of
      osteoporosis in RA.

PMID- 15508790
TI  - [Effect of heavy metal ions on function of vascular endothelium in patients with
      ischemic heart disease].
AB  - Endothelium dysfunction is one of the first signs of atherosclerotic process.
      There are many factors known, which provoke such a dysfunction; many are still to
      be revealed. One of them may be a heavy metal ion. The aim of the study was to
      establish the link between heavy metal ions concentrations in blood and the
      endothelium dysfunction measured with the nitric oxide blood concentration in a
      population of patients with ischemic heart disease, not exposed occupationally to
      high concentrations of heavy metal ions. The study included 42 patients (24 men
      and 18 women, age 63.7 +/- 9.9 years) with angiography confirmed coronary artery
      disease. The study group was subdivided according to coronary artery
      atherosclerosis extent. Control included 18 patients (10 men and 8 women, age
      58.7 +/- 9.4 years), where coronarography revealed no significant lesions in
      coronary arteries. In all persons blood for nitric oxide and heavy metal ions was
      collected. Heavy metal ions studied included: lead, copper, manganese, zinc,
      selenium, and cadmium. Heavy metal ions concentrations in studied and control
      group was within normal range for not exposed population and did not differ
      significantly with each other. No significant difference was observed between
      groups for nitric oxide concentration. Nitric oxide concentration correlated
      positively with zinc concentration in control group (p<0.001, Pearson r=0.70).
      Such a correlations was not present in studied group. After regression analysis
      there was still strong correlation between zinc and nitric oxide in control group
      (beta=0.43, p<0.01), the phenomenon not present in studied group. CONCLUSIONS: 1.
      In the group of patients with angiography confirmed ischemic heart disease heavy
      metal ions concentrations are within normal range for not exposed population and
      is not connected with coronary atherosclerosis extent. 2. From all heavy metal
      ions studied only zinc seams to have protective influence on endothelial function
      measured by nitric oxide production 3. No such a protective effect is observed in
      the group of patients with ischemic heart disease, which may be due to the
      relative zinc deficiency.

PMID- 15508791
TI  - [Assessment of the usefulness of the presence of antithyroid peroxidase
      antibodies (TPOAb) in patients with end-stage renal failure treated with
      hemodialysis].
AB  - Due to a high frequency of autoimmune diseases in patients with ESRF we observed
      for 4 years 8 patients treated with HD with high level of TPOAb and 8 patients
      without TPOAb. Aim of the study was to estimate the role of TPOAb as a prognostic
      factor of hypothyreosis. We observed in a 4-years follow-up significant increase
      of TSH (p<0.05) in patients with high TPOAb level. fT3 and fT4 did't change in
      this time. In the group without TPOAb we observed significant (p<0.01) decrease
      of fT3 probably due to the disturbances in T4 to T3 conversion. Our results don't
      permit us to draw a final conclusions but induce us to further observation of
      hypothyreosis development in patients with ESRF.

PMID- 15508792
TI  - [Cardiopulmonary exercise testing and cytokines in chronic heart failure.
      Comparison of patients with ischaemic and with dilated cardiomyopathy].
AB  - Heart failure (HF) is a complex clinical syndrome due to ischaemic heart disease,
      idiopathic cardiomyopathy, hypertension, valve heart disease and others. It is
      not clear if the etiology of HF influences decreased in this syndrome exercise
      tolerance. Controversial is also dependence of cytokine levels on etiology of HF.
      The aim of the study was to compare exercise capacity and cytokines levels in pts
      with ischaemic and dilated cardiomyopathy. We analyzed circulating levels of TNF
      alpha and its soluble receptors sTNF-RI and sTNF-RII, and interleukin-1beta (IL
      1beta), and interleukin-6 (IL-6) in 41 pts with CHF, functional class NYHA I-IV,
      mean EF--25.2 +/- 7.1%. For determination of cytokines level (using R & D System
      tests) venous blood was withdrawn after 30 minutes of supine rest. All underwent
      echocardiography and cardiopulmonary exercise stress testing. Dilated
      cardiomyopathy (DCM) was diagnosed in 21 pts, ischaemic (ICM) in 20 pts. Pts with
      DCM were younger then with ICM (48 +/- 6.6 vs 56 +/- 6.6 yrs; p = 0.001). There
      were no significant differences between groups concerning BMI and EF. There were
      no significant differences in the level of TNF-alpha and sTNF-RI between groups.
      There was a trend of increased sTNF-RII in pts with ICM (3179.7 +/- 832.7 vs 2699
      +/- 680.1 pg/ml; p = 0,07), IL-1beta (2.55 +/- 2.41 vs 1.49 +/- 1.68 pg/ml; p =
      0.087) and IL-6 (6.25 +/- 2.21 vs 4.98 +/- 3.64 pg/ml; p = 0.065), and
      significant increased ESR (11.2 +/- 9.5 vs 5.5 +/- 4.7 mm/h; p = 0.04). Peak VO2
      was reduced in pts with ICM group as compared to those with DCM (14.1 +/- 3.7 vs
      18.1 +/- 4.8 ml/kg/min; p = 0.0069). In chronic heart failure circulating levels
      of cytokines tended to be higher in pts with ischaemic origin of the syndrome.
      The exercise capacity is lower in ischaemic cardiomyopathy.

PMID- 15508793
TI  - [Pharmacological versus invasive treatment in patients with atrial fibrillation].
AB  - Aim of this prospective study was to assess quality of life (QoL), left
      ventricular (LV) function and exercise performance in two groups of patients
      (pts) with atrial fibrillation (Af) treated with: radiofrequency catheter
      ablation (RFA) and antiarrhythmic drugs (AA). Between 1996 and 2000 - 74
      patients, 28 women, with drug refractory Af were enrolled by clinical indications
      for two modes of therapy: RFA and AA. RFA group consisted of 38 pts, 63.7 +/-
      11.5 years old: 28 pts with RF AV Node ablation and pacemaker implantation (PI)
      and 10 pts with AV Node modification or right atrial isthmus RF ablation due to
      Af conversion to atrial flutter (Aflu) during medical therapy. AA group consisted
      of 36 pts, aged 59.7 +/- 13.8 years. Patients from RFA group suffered
      significantly more serious diseases than pts from AA group. No significant
      (sign.) differences between two groups were found in age, gender, arrhythmia
      history and number of AA taken. Pts were analyzed before entry, after 3 and 12
      months of follow-up (3 mo. FU, 12 mo. FU) with following indices: LV function
      (Echo: EF & FS), exercise performance (treadmill test), QoL questionnaires,
      number of hospital admissions connected to arrhythmia or procedures (RFA & PI),
      number of AA drugs taken in RFA group. RFA group: Two deaths occurred due to end
      stage respiratory insufficiency (COPD), one pt required reposition of pacemaker
      lead. AA group: 3 pts required RFA due to uncontrolled Af/Aflu (AV Node ablation
      with PI - 1 pt, right atrial isthmus ablation - 2 pts). Analysis of two patients
      groups: LV function: Sign. improvement (EF & FS) in both groups in 12 mo. FU;
      Exercise performance: no sign. changes in 3 and 12 mo. FU. QoL: Arrhythmia scale:
      3 mo. FU sign. reduction in both groups; 12 mo. FU reduction in RFA group only;
      Anxiety scale: 3 and 12 mo. FU sign. reduction of anxiety level in RFA group;
      Exercise and activity scales: 3 and 12 mo. FU sign. improvement in RFA group.
      During 3 and 12 mo. FU sign. less pts from RFA group required hospital admission
      versus pts from AA group. Sign. reduction in AA was noted in RFA group. Patients
      with symptomatic Af treated with RFA benefit from this kind of therapy more than
      patients treated with AA. Quality of life improvement visible in short term
      observation in patients from RFA group is still present after one year
      observation. Improvement in LV function is observed after one year in both groups
      of pts with Af.

PMID- 15508794
TI  - [Early development of Charcot neuroarthropathy in the course of compensated
      diabetes mellitus--case report].
AB  - Charcot neuroarthropathy (CN)--chronic and progressive, destructive disease of
      bones and joints, which develops on the background of neuropathy, is late and
      uncommon complication of diabetes. It occurs almost exclusively in patients with
      a mean duration of diabetes at least 10 years. We report the case of woman, who
      developed an acute phase of CN 11 months after recognition of diabetes. Because
      of recent recognition of diabetes and good glycaemic control, CN wasn't
      considered in the differential diagnosis of swelling, pain and warmth of feet.
      The initial diagnosis was missed, leading in few months, to development of
      irreversible deformity of both feet.

PMID- 15508796
TI  - [Exercise-induced asthma; clinical presentation, pathogenesis and treatment].

PMID- 15508795
TI  - [Hypercalciuria with severe hypocalcaemia in association with distal renal
      tubular acidosis--case report and differential diagnostics].
AB  - Neither severe distal renal tubular acidosis nor hypercalciuria have been
      recognized to cause severe hypocalcaemia. We describe a 53 years old woman with
      distal renal tubular acidosis and hypercalciuria who demonstrated severe
      hypocalcemia, normalized after calcium and vitamin D supplementation and
      treatment with thiazide.

PMID- 15508797
TI  - [The role of anti-endothelial cell antibodies in the pathogenesis of vascular
      complications in systemic lupus erythematosus].

PMID- 15508798
TI  - [Schnitzler's syndrome].

PMID- 15508799
TI  - [Molecular mechanisms of anti-inflammatory actions of glucocorticoids and their
      synergy with beta2-agonists].

PMID- 15508800
TI  - [Endothelial nitric oxide and physical activity in cardiovascular diseases].

PMID- 15508801
TI  - [The primary vasculitides].

PMID- 15508803
TI  - [Pulse pressure as a prognostic indicator of organ damage in patients with
      essential hypertension].
AB  - Pulse pressure (PP), defined as systolic blood pressure minus diastolic blood
      pressure, plays an important role as a risk factor for cardiovascular events.
      Pulse pressure is pulsatile component of blood pressure. A widened pulse pressure
      reflects increased stiffness of the large arteries. The aim of the study was to
      evaluate the association between pulse pressure and organ damage in essential
      hypertension. We examined 60 subjects, 34 women aged 59 +/- 13 years and 26 men
      aged 48 +/- 17 years with primary hypertension. In every subject we performed 24
      hour automatic blood pressure measurement and echocardiography, abdominal
      ultrasonography, funduscopy, chest x-ray. We measured sodium potassium,
      creatinine level in serum and in urine, creatinine clearance and
      microalbuminuria. Pulse pressure is proportional to the stage of hypertension. A
      dimension of the aorta parallels with measures of blood pressure. The strong
      correlation between pulse pressure and damage in funduscopy can indicate, that
      complication in fundus of the eye are dependent more than the level of a
      pressure. The significantly higher sodium level in serum and the positive
      correlation between natremia, natriuresis and pulse pressure proves the role of
      natrium in pathophysiology of hypertension.

PMID- 15508802
TI  - [Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS) in men
      with coronary artery disease].

PMID- 15508804
TI  - [Leisure time physical activity and subjective health state in adults].
AB  - BACKGROUND: Leisure time physical activity improves health. AIM: The aim of this
      study was to analyze association between leisure time physical activity level and
      subjective health state in adults. MATERIAL AND METHODS: We have analyzed level
      of recreational physical activity and subjective health state in representative
      sample of 1029 adult people in Lodz including 488 men and 541 women. Physical
      activity assessment was carried out by the interviewer-administrated Seven-Day
      Physical Activity Recall (SDPAR). Indeed physical activity, subjective health
      state and physical fitness determined by maximal oxygen output (VO(2max)) was
      assessed in 271 objectively healthy people. Subjective health state was
      determined by visual analogue score taken from standardized questionnaire EuroQol
      5D. RESULTS. More than half of subjects (60.8%) did not participate in leisure
      time sport activities. The number of those who had from 1 to 999 kcal/week, on
      sport was 23.4%. Only 15.,8% participants spent on leisure time physical activity
      more than 1000 kcal/week. In both groups (total n = 1029 and healthy people n =
      271) subjects with 0.0 kcal/week energy expenditure on leisure time sport
      activities reported significantly lover subjective health state scores comparing
      to people with higher especially 1000-1999 kcal/week energy expenditure. In this
      study significant correlation was found for energy expenditure on leisure time
      physical activity and subjective health state (in group n = 1029 r = 0.03, p <
      0.0001 and in group n = 271 r = 0.4, p < 0.0001). CONCLUSIONS: This study
      demonstrates that 80.4% of subjects did not achieve the level of physical
      activity recommended by experts in health promotion and prevention of
      cardiovascular and other chronic diseases. Level of leisure time physical
      activity influence subjective health state in adults.

PMID- 15508805
TI  - [Renin aldosterone profile in essential hypertension during pregnancy and after
      delivery].
AB  - BACKGROUND: The pathogenesis of essential hypertension (EH) is a complex
      multifactorial process. Little is known about the association between pregnancy
      and blood pressure fluctuation in women with EH. In this study we wanted to
      evaluate the relationship between the blood pressure (BP) and plasma renin
      activity (PRA) as well as serum and urine aldosterone (ALDO) levels in pregnant
      women with essential hypertension. MATERIALS AND METHODS: We analyzed 84 pregnant
      women (97% primigravida) with EH aged 22-40 (mean 29.5 +/- 5.4) years and 60
      healthy pregnant women aged 22-40 (mean 28.5 +/- 4.9) years. In women with EH,
      antihypertensive therapy was stopped immediately after pregnancy was confirmed.
      Patients with EH were divided to two groups: 1) with BP > or = 140/90 and 2) with
      BP > or = 140/90. PRA and ALDO as well as sodium and potassium excretion were
      measured three times in different periods of pregnancy: 8-12 weeks, 24-28 weeks,
      34-38 weeks. In addition, both PRA and ALDO were analyzed in 4th month after
      delivery i.e. in the time, in which woman is reached hormonal and hemodynamic
      stability. PRA and ALDO were determined by RIA methods. BP was monitored by
      standardized method using mercury manometer. RESULTS: PRA and ALDO concentrations
      in both: serum and urine were increased during pregnancy in all studied groups.
      No difference in kinetics of PRA and ALDO was stated between healthy pregnant
      women with EH. Increased was observed in women and during pregnancy.
      Statistically significant, the highest level of PRA was noted in fourth month
      after delivery in women with BP > 140/90. In this period, however, concentrations
      of ALDO in both serum and urine were the same in all examined women. CONCLUSION:
      1. In women with EH and BP < 160/100 mm Hg during pregnancy PRA and concentration
      of ALDO in serum as well as ALDO excretion were the same as in healthy pregnancy
      women. 2. Reduction of blood pressure was observed in the group of women with the
      lowest PRA in fourth month after delivery. 3. PRA measured in women with EH may
      be a predictive parameter of BP during pregnancy.

PMID- 15508806
TI  - [Melatonin concentrations and other parameters of blood antioxidant defense
      system in elderly men with various levels of physical activity].
AB  - It is well documented that regular physical activity and increased levels of
      melatonin may enhance the blood antioxidant system. The aim of the present study
      was to evaluate the antioxidant defense mechanisms, in particular, the
      antioxidant potential of melatonin in groups of elderly men (mean age 70 years),
      marked of on the basis of habitual physical activity level. To estimate the
      physical activity of the study population, weekly energy expenditure was measured
      in each subject with a Caltrac accelerometer. The study population was divided
      into two groups (31 subjects in each group) according to the criteria proposed by
      Bauman: less active (energy expenditure below 1600 kcal per week) and more active
      (energy expenditure 1600 kcal per week). Venous blood samples were taken from
      each subject for assessment of plasma total antioxidant status (TAS),
      thiobarbituric acid reactive substances (TBARS) concentrations and melatonin
      (MLT) levels. The reduced glutathione (GSH) content and glutathione peroxidase
      (GPx) activity in hemolyzed red blood cells were also measured. A significant (p
      < 0.05), inverse Spearman correlation between MLT concentrations in plasma and
      physical activity levels was observed in the group of less active men. In more
      active subjects, a positive correlation between GSH and TAS levels (p < 0.05) and
      inverse correlations between GSH and TBARS concentrations (p < 0.05), TAS and
      TBARS levels (p < 0.01) and between TAS and MLT levels (p < 0.001) were noted.
      The results of the present study support the view that melatonin plays an
      important role in the blood antioxidant defense system in elderly men and
      indicate that habitual physical activity may have an influence on the plasma
      levels of melatonin.

PMID- 15508807
TI  - [Chronic complications in adult patients with newly diagnosed diabetes mellitus
      in relation to the presence of humoral autoimmune markers against pancreatic
      islet cells].
AB  - Latent autoimmune diabetes in adults (LADA) is subtype of diabetes type 1. It is
      well know, that 50% patients with new diagnosed diabetes type 2 present late
      complications. As far we don't know how many patients with new diagnosed diabetes
      have late complications according to presence of antibodies against islet
      antigens. The aim of the study was to compare late complications of diabetes:
      microangiopathy and macroangiopathy in newly diagnosed adult diabetic patients in
      relation to presence of humoral autoimmune markers. MATERIAL AND METHODS: We
      evaluated the presence of late complications in group of 41, hospitalized
      patients base on clinical examination and medical history. Glutaminic acid
      decarboxylase antibodies (anti-GAD), protein tyrosine phosphatase antibodies
      (anti-IA-2) and anti-insulin antibodies (IAA) titers were measured by RIA. The C
      peptide basal and stimulated, HbA1c, glucose, total cholesterol, HDL cholesterol,
      LDL cholesterol, triglycerides, urea, creatinine levels and microalbuminuria were
      evaluated. RESULTS: The presence of islet cell specific antibodies were shown in
      25 subjects. We observed late complications in 13/25 (52%) in group with positive
      antibodies titers, and in 10/16 (62.5%) in group without antibodies. We diagnosed
      the nephropathy (16% vs 6.25%), retinopathy (12% vs 0%), polyneuropathy (20% vs
      12.5%), hypertension (32% vs 50%), chronic heart disease (8% vs 25%), overweight
      (32% vs 50%) and hyperlipidemia (12% vs 25%) respectively in subjects with and
      without antibodies. The concentrations of total cholesterol (185 +/- 47.8 vs 218
      +/- 38.7, p < 0.05) and creatinine level (0.8 +/- 0.15 vs 0.95 +/- 24, p < 0.05)
      were higher in group without antibodies, but fasting glycemia (181 +/- 69.1 vs
      132 +/- 32.8, p < 0.05) was higher in the group presenting with autoantibodies.
      We did not observed the difference between level of glycosylated hemoglobin in
      the investigated groups. RESULTS: There is the tendency to higher incidence of
      microangiopathy in group of patients positive to islet cell antibodies.
      Conversely the macroangiopathy appears frequently in patients without antibodies.

PMID- 15508808
TI  - [Computerized tomography in the diagnosis of nonalcoholic fatty liver--comparison
      with liver biopsy].
AB  - The frequency of nonalcoholic fatty liver disease (NAFLD) is high, an estimated
      10-25% of the population in different countries. Due to the lack of specific
      symptoms or irregularities in laboratory examinations the major role in diagnosis
      is played by, apart form liver biopsy, the imaging examinations. AIM: The
      assessment of the correlation between intensity of fatty liver in computed
      tomography (CT) and in liver biopsy. INVESTING GROUP AND METHOD: The initial
      group comprised of 147 patients who had undergone CT of the abdomen. Within this
      group the range of attenuation coefficient in Hansfield units was measured in
      certain areas of liver and spleen. Density of the tissues being given (in
      Hansfield units) the increase of the fat content in the liver above the norm
      (tKT) was calculated, according to the formula: tKT = [(spleen density in OH
      units + 4 OH units) - liver density in OH units] x 0.8 = fat above norm in mg/l g
      of the liver tissue. Out of this group 12 patients (8 men and 4 women, average
      age 45.9 +/- 14.5 years) with clinical features of NAFLD on clinical indications
      for liver biopsy were selected. RESULTS: 3 patients the received value of tKT was
      found to be correct, that is tKT < 0. In these patients the estimated percentage
      of hepatocytes affected by steatosis (%TB) reached 5-20%. In the subgroup that
      comprised if the folio wing 6 patients %TB ranged from 30 to 70% and tKT--from
      3.2 to 10. In the group of patients with the highest %TB, reaching 100%, the tKT
      value reached respectively 5, 10.8 and 13.6. The analysis of the relation between
      %TB and tKT showed a linear correlation of these two parameters. Following the
      increase of the intensity of the fatty liver in the biopsy the value of tKT
      rises. CT of the liver with the range of attenuation coefficient marked (in
      Hansfield units) is a useful tool for quantitative assessment of the fatty pulp.

PMID- 15508809
TI  - [Assessment of the quality of ambulatory care in type 2 diabetes mellitus].
AB  - INTRODUCTION: Long asymptomatic course of diabetes and insufficient treatment
      lead to many chronic complications. AIM OF STUDY: Assessment of the quality of
      ambulatory diabetes care in Szczecin and nearest region. MATERIAL AND METHODS: In
      year 2001 patients with previously diagnosed diabetes hospitalized in 35 wards of
      several hospitals in Szczecin were inquired for data concerning ambulatory care
      before hospitalization. STUDY GROUP: 120 subjects (60 women and 60 men), aged 65
      +/- 13 years, diabetes duration 9.1 +/- 7.1 years. Type 2 diabetes--104 cases,
      type 1-10 cases, other types of diabetes--6 cases. RESULTS: Health care was
      provided by general practitioners (GPs) for 63% of patients, by diabetologist for
      31% of them; 6% stayed out of control. In the proceeding month 49% of subjects
      attended visit related to diabetes; in 10% such a visit was reported in the
      period longer than 6 months. Glucose measurement performed every day was reported
      by 28% of subjects, once a month--by 36%, rarely--by 15%. Blood pressure
      measurements were performed by doctors in 43% of subjects, self control was
      performed by 42% of them and in 10% blood pressure was not measured at all. In
      the proceeding year eyes examination related to diabetes was performed in 63% of
      patients; in 26% such examination was never done. Foot examination was never done
      in 66% of diabetics. ECG examination was done in 57% of subjects last year, in
      39% it was never done. Cholesterol serum level was measured last year in 52% of
      subjects. CONCLUSIONS: 1. Quality of ambulatory diabetes care is highly
      unsatisfactory and insufficient. 2. To improve health care for diabetics
      obligatory training in practical diabetology was conducted for all GPs from north
      west region of Poland in 2002 y.

PMID- 15508810
TI  - [Early form of toxoplasmosis with accompanying enlargement of lymph nodes].
AB  - The paper describes a case of a 42-year-old female presented rapidly increasing
      enlargement of lymph nodes. Initially it was believed to be an effect of
      proliferous systemic changes. The diagnostic procedures did not confirm the
      initial diagnosis but they evoked a lot of stress of the patient as well as her
      psychic discomfort resulting from a number of biopsies. Serological tests carried
      out in the further course of the diagnostic procedure showed that the increased
      nodular reaction should be attributed to Toxoplasma gondii invasion, which was
      indicated by the presence of IgM and IgA antibodies and low avidity of IgG. The
      early administration of specific treatment with spiramycin led to the regression
      of the clinical symptoms and gradual normalization of the serological test. The
      case is worth attention for several reasons: 1. it indicates that it is necessary
      to consider T. gondii infection in basic clinical practice, which is frequently
      ignored, 2. it illustrates the effectiveness of early specific treatment, 3. it
      demonstrates the importance of well selected and properly interpreted
      microbiological tests.

PMID- 15508811
TI  - [Hereditary hemochromatosis: molecular diagnosis and effect of treatment].
AB  - Hereditary hemochromatosis is a genetic disorder, inherited as an autosomal
      recessive trait, characterized by iron overload. A single mutation (C282Y) in the
      HFE gene is found in more than 90% of these patients. We report the case of a 50
      year-old man, with clinical symptoms of hemochromatosis, who was found to be
      homozygous for the C282Y mutation. We present the results of therapeutic
      phlebotomy after one year of the treatment. Genetic tests were performed on the
      patient's close relatives and revealed that his son was also homozygous for the
      C282Y mutation. Early phlebotomy could prevent iron deposition and organ damage
      in this patient. Genetic determining of the HFE mutations is a useful noninvasive
      method of diagnosing hereditary hemochromatosis.

PMID- 15508812
TI  - [Helicobacter pylori alcohol dehydrogenase (HPADH)--characteristics and role in
      the pathogenesis of diseases associated with Helicobacter pylori infection].

PMID- 15508813
TI  - [Endocrine disorders as a result of alcohol abuse].

PMID- 15508814
TI  - [Preoperative respiratory system evaluation and basic standards of management in
      respiratory insufficiency].

PMID- 15508815
TI  - [Statins--the panacea of the turn of the century?].

PMID- 15508816
TI  - [Fabry's disease as a cause of chronic renal failure].

PMID- 15508817
TI  - [Molecular mechanisms of osteoarthritis].

PMID- 15508818
TI  - [Differentiation and apoptosis of adipocytes--the role of tumor necrosis factor
      (TNF-alpha)].

PMID- 15508820
TI  - [The Fourth Congress of the European Federation of Internal Medicine, Berlin,
      September 10-13, 2003].

PMID- 15508819
TI  - [Treatment of pulmonary alveolar proteinosis by whole-lung lavage technique].

PMID- 15508821
TI  - An idea from across the Atlantic.

PMID- 15508822
TI  - First among equals.

PMID- 15508823
TI  - Spotlight on success. Jan Grant.

PMID- 15508824
TI  - The children's national service framework: from policy to practice.

PMID- 15508825
TI  - Right from the start.

PMID- 15508826
TI  - Improving the patient experience: a focused approach to improving care.

PMID- 15508827
TI  - Leadership effectiveness: using partnership to develop targeted leadership
      training.

PMID- 15508828
TI  - The challenge of relationship boundaries in mental health.

PMID- 15508829
TI  - Return to the future.

PMID- 15508830
TI  - Combined analysis of the essential oil of Chenopodium ambrosioides by GC, GC-MS
      and 13C-NMR spectroscopy: quantitative determination of ascaridole, a heat
      sensitive compound.
AB  - A commercial sample of the essential oil of Chenopodium ambrosioides L. from
      Madagascar was analysed by GC, GC-MS and 13C-NMR. By GC analysis, the major
      constituents were found to be ascaridole (1) (41.8%), isoascaridole (2) (18.1%),
      p-cymene (16.2%), alpha-terpinene (9.7%) and limonene (3.8%). However, ascaridole
      undergoes a partial thermal isomerisation to 2 and hence the amount of 1 is under
      estimated by GC analysis. The actual contents of 1 and 2 (55.3 and 4.6%,
      respectively) were obtained following combined analysis of the sample by GC and
      13C-NMR. Several hydroxy- and polyhydroxy-menthanes were identified by 13C-NMR.

PMID- 15508831
TI  - Chemical fingerprinting of Andrographis paniculata using HPLC, HPTLC and
      densitometry.
AB  - An attempt has been made to develop a method by which to determine the chemical
      fingerprint of Andrographis paniculata (Acanthaceae). High-performance thin layer
      chromatography (HPTLC) was used to analyse hexane, chloroform, methanol and water
      extracts of leaves of A. paniculata. A computerised densitometer was applied to
      the two-dimensional spectrographic image analysis of the HPTLC plates. An HPLC
      equipped with a photodiode array detector was used for the analyses of these
      different extracts. The analyses showed that andrographolide and
      neoandrographolide are absent in the hexane extract but are present in greater
      amounts in the methanol extract as compared with the other extracts. These
      chromatograms may serve as a chemical fingerprint of the drug A. paniculata for
      quality control purposes and in the preparation of formulations based on the
      drug.

PMID- 15508832
TI  - Seasonal, populational and ontogenic variation in the volatile oil content and
      composition of individuals of Origanum vulgare subsp. Hirtum, assessed by GC
      headspace analysis and by SPME sampling of individual oil glands.
AB  - Small-scale GC headspace analyses combined with SPME sampling of individual oil
      glands have been used to measure the variation in volatile content and
      composition in and within different oregano plants as affected by age, season and
      developmental state. The main monoterpenes found were p-cymene, carvacrol and
      their precursor gamma-terpinene. The early season preponderance of p-cymene over
      carvacrol was reversed as the season progressed and this pattern could also be
      seen at any time within the plant, from the latest leaves to be produced (low in
      cymene) to the earliest (high in cymene). Seedlings from the same mother plant
      developed this pattern at different rates. Within individual leaves the pattern
      was not observed, even within the youngest developing leaves. However it was
      found that the oil composition of individual glands within a single leaf varied
      considerably, most notably in respect of the production of carvacrol and its
      isomer thymol.

PMID- 15508833
TI  - Isoflavonoids in the Rutaceae family: 1. Fortunella obovata, Murraya paniculata
      and four Citrus species.
AB  - Several types of compounds with immunoreactivity similar to isoflavonoids were
      detected in water: ethanol extracts of leaves of Fortunella obovata Hort. ex
      Tanaka, Murraya paniculata Jack. and four Citrus species, namely C. aurantium L,
      C. grandis Osbeck, C. limonia Osbeck., and C. sinensis Osbeck (Rutaceae). The
      chromatographic mobilities of the immunoreactive substances were compared with
      those of authentic standards, revealing a spectrum of isoflavonoid metabolites in
      all plants studied. Aglycones as well as glycosides were recognized, namely
      daidzin, genistin, daidzein, genistein, formononetin, biochanin A, prunetin, and
      several incompletely characterized isoflavonoids. A subsequent HPLC-MS study
      verified the identities of the main immunoreactive isoflavonoids and established
      the identities of several others, viz. glycitein, glycitin, ononin and sissotrin,
      including the malonylated and acetylated isoflavonoid glucosides. The estimated
      content of the individual immunoreactive entities ranged from a few microg to
      about 2 mg/kg (dry weight). It is concluded that the isoflavonoid metabolic
      pathway is present throughout the Rutaceae family.

PMID- 15508834
TI  - High-performance liquid chromatography-coordination ion spray-mass spectrometry
      (HPLC-CIS/MS): a new tool for the analysis of non-polar compound classes in plant
      extracts using the example of Piper methysticum Forst.
AB  - An efficient method to characterise complex plant extracts is described using the
      example of Piper methysticum Forst. (kava; Piperaceae). The method is based on
      the on-line coupling of high-performance liquid chromatography to a new detection
      technique: coordination ion spray-mass spectrometry (CIS/MS). CIS/MS is a
      universal, novel ionisation technique improving selectivity as well as
      sensitivity. Charged complexes were formed through addition of central complexing
      ions such as sodium, silver and cobalt. The advantages of CIS/MS detection
      compared with the electrospray ionisation detection are discussed. The
      experimental set-up and the application of this simple and robust technique is
      described to show the its various fields of application in the analysis of plant
      extracts.

PMID- 15508835
TI  - Solvent effects on focused microwave assisted extraction of polyphenolic acids
      from Eucommia ulmodies.
AB  - An open microwave-assisted extraction system was used to extract gallic acid,
      protocatechuic acid, chlorogenic acid and caffeic acid from Eucommia ulmodies.
      The effect of extraction variables, especially solvent, on the recoveries of
      these polyphenolic compounds was investigated using factorial design. As
      extracting solvent for these compounds, methanol produced a higher recovery than
      pure water. For straight chain alcohol solvents, the lower the carbon number, the
      higher the recoveries of the polyphenolic acids. The optimal ratio of
      methanol:water:glacial acetic acid in the solvent mixture used in microwave
      assisted extraction was 2:8:0.3 (v/v) and this solvent could be directly used as
      the mobile phase in HPLC separation without additional intermittent treatment as
      reported in literature. The extraction under the condition of 50% microwave power
      and 30 s irradiation at a solvent:sample ratio of 10 (mL/g) was found to be the
      most advantageous. The repeatability test of extraction and chromatographic
      analysis was satisfactory for the analysis of these polyphenolic compounds.

PMID- 15508837
TI  - Determination of isopropylmethylphenols in black seed oil by differential pulse
      voltammetry.
AB  - A differential pulse voltammetric method is presented for the determination of
      isopropylmethylphenols (carvacrol and/or thymol) in phytotherapeutic black seed
      oils. The voltammetric behaviours of these phenols were examined in various
      buffer systems over the pH range 3.5-10.0. In Sorensen buffered methanol solution
      (3:7; v:v; pH 8.5), the differential pulse voltammograms exhibited reproducible
      peaks at Ep + 0.49 V vs. silver-silver chloride-potassium chloride 3 M for both
      carvacrol and thymol. Under these conditions, a plot of peak height against
      concentration of the isopropylmethylphenols was found to be linear over the range
      0.25-2.5 microg/mL (r = 0.999). The detection limit was 0.04 microg/mL. The
      described voltammetric method was tested on two black seed oils available on the
      Austrian market.

PMID- 15508836
TI  - Effect of extraction method on the yield of furanocoumarins from fruits of
      Archangelica officinalis Hoffm.
AB  - Optimal conditions for the extraction and analysis of furanocoumarins from fruits
      of Archangelica officinalis Hoffm. have been determined. The following extraction
      methods were used: exhaustive extraction in a Soxhlet apparatus, ultrasonication
      at 25 and 60 degrees C, microwave-assisted solvent extraction in open and closed
      systems, and accelerated solvent extraction (ASE). In most cases the yields of
      furanocoumarins were highest using the ASE method. The effects of extracting
      solvent, temperature and time of extraction using this method were investigated.
      The highest yield of furanocoumarins by ASE was obtained with methanol at 100-130
      degrees C for 10 min. The extraction yields of furanocoumarins from plant
      material by ultrasonication at 60 degrees C and microwave-assisted solvent
      extraction in an open system were comparable to the extraction yields obtained in
      the time- and solvent-consuming exhaustive process involving the Soxhlet
      apparatus.

PMID- 15508838
TI  - Quantitative analysis of ginkgolic acids from Ginkgo leaves and products using 1H
      NMR.
AB  - The determination of ginkgolic acids in Ginkgo products is one of the principal
      components of quality control. However, a number of ginkgolic acids with
      different side chains may be present and this makes their analysis by
      conventional chromatographic methods more complex. In this study, 1H-NMR
      spectrometry was applied to the analysis of the total content of ginkgolic acids
      in leaves of Ginkgo biloba and in six types of commercial Ginkgo products in the
      absence of chromatographic purification. For this analysis, protons H-3, H-4, and
      H-5, which are well separated in the range 8 (ppm) 6.5-7.5 in the 1H-NMR
      spectrum, were utilised. For further confirmation, the correlations of H-3, H-4
      and H-5 were examined by 1H-1H COSY spectra in all extracts. The quantity of the
      compounds was calculated from the relative ratio of the integral of each peak to
      the integral of the peaks of a known amount (100 microg) of anthracene used as an
      internal standard. The quantitative results obtained by 1H-NMR analysis were
      compared with those obtained by GC, which showed that the 1H-NMR method allows a
      simple quantification of total ginkgolic acids in Ginkgo extracts without any pre
      purification steps.

PMID- 15508839
TI  - Current awareness in phytochemical analysis.

PMID- 15508840
TI  - Mycoplasma species and related organisms isolated from ruminants in Britain
      between 1990 and 2000.
AB  - Between 1990 and 2000, more than 1600 mycoplasmas and the related acholeplasmas
      were identified from ruminant animals by the Mycoplasma Group at the Veterinary
      Laboratories Agency--Weybridge. Mycoplasma bovis was the most commonly identified
      pathogen, mostly from pneumonic calves but occasionally from cattle with mastitis
      and arthritis. Mycoplasma canis was first isolated in Britain in 1995 from
      pneumonic calves and the number of isolates increased to 18 per cent of the total
      mycoplasmas isolated from cattle in 1999. The ELISA for antibodies to M. bovis
      detected 1971 positive samples (22 per cent) among 8959 serum samples, mainly
      from pneumonic cattle. Other mycoplasmas identified included Mycoplasma dispar
      from the lungs of cattle with respiratory disease, and Mycoplasma bovigenitalium
      from the reproductive tract of cows with vulvovaginitis and infertility.
      Mycoplasma bovirhinis and Acholeplasma species were found commonly but are
      thought to be more opportunistic than pathogenic. In sheep and goats, the
      majority of Mycoplasma species isolated were identified as Mycoplasma
      ovipneumoniae from pneumonic sheep, Mycoplasma conjunctivae from sheep with
      keratoconjunctivitis, and the ubiquitous Mycoplasma arginini.

PMID- 15508841
TI  - Normal echoanatomy of the red-eared slider terrapin (Trachemys scripta elegans).
AB  - Thirty red-eared slider terrapins (Trachemys scripta elegans) were examined by
      ultrasound to establish the normal ultrasonographic appearance of their coelomic
      structures. They were not sedated, and owing to their small size they were
      examined through the inguinal window of the carapace. High resolution transducers
      (7.5 and 11 MHz) enhanced the ultrasonographic imaging of the bowel, urinary
      bladder, liver, gall bladder, heart, kidney and gonads, but the pancreas, adrenal
      glands, thyroid glands and spleen could not be visualised.

PMID- 15508842
TI  - Pacing as a clinical sign in cattle with bovine spongiform encephalopathy.

PMID- 15508843
TI  - Outbreak of epizootic haemorrhagic disease on the island of Reunion.

PMID- 15508844
TI  - Monorchidism in an appaloosa stallion.

PMID- 15508845
TI  - Isolation of Serratia, Arcanobacterium and Burkholderia species from visceral and
      cutaneous abscesses in four emaciated ewes.

PMID- 15508846
TI  - Disseminated Histoplasma capsulatum var capsulatum infection in a captive mara
      (Dolichotis patagonum).

PMID- 15508847
TI  - International trade in livestock and livestock products: the need for a commodity
      based approach.
AB  - International animal health standards designed to facilitate safe trade in
      livestock and livestock products are set by the Office International des
      Epizooties (OIE) under the Sanitary and Phytosanitary Agreement of the World
      Trade Organization (WTO) and documented in the OIE's Terrestrial Animal Health
      Code. A core principle of the Code is the need for countries to eradicate
      important transboundary animal diseases (TADs) to reduce the risk of exporting
      disease to trading partners. International food safety standards are set by the
      Codex Alimentarius Commission, administered jointly by the World Health
      Organization and the Food and Agriculture Organization of the United Nations. The
      goal of global eradication of most TADs is unachievable for the foreseeable
      future, other than in the case of rinderpest, and this prevents many countries,
      especially developing nations, from engaging in international trade under WTO
      rules. This paper proposes an alternative, commodity-based approach to the
      formulation of international animal health and food safety standards, based on
      the fact that different commodities pose very different risks when it comes to
      the spread of human and animal pathogens. Therefore, the risk mitigation
      strategies required are equally commodity-dependent. The authors conclude that
      more focused commodity standards would improve access to international markets
      for all countries, especially those in the developing world. For this objective
      to be realised, credible and independent certification is required.

PMID- 15508848
TI  - Identification of a European bat lyssavirus type 2 in a Daubenton's bat found in
      Staines, Surrey, UK.

PMID- 15508849
TI  - FMD and the contiguous cull.

PMID- 15508850
TI  - FMD and the contiguous cull.

PMID- 15508851
TI  - Unified vet-help charity.

PMID- 15508852
TI  - DEFRA/ADAS animal welfare promotion.

PMID- 15508853
TI  - Early neutering of cats.

PMID- 15508854
TI  - Improving safety in health care environments--Institute of Medicine report.

PMID- 15508855
TI  - What are some effective chronic disease management strategies that can be used in
      case management?

PMID- 15508856
TI  - Physical examination--examen fisico.

PMID- 15508857
TI  - Implementation of a scheduled toileting program in a long term care facility:
      evaluating the impact on injury risk to caregiving staff.
AB  - This study evaluated the impact of a scheduled toileting program on the risk of
      injury to caregivers and on resident agitation or aggressive behaviors. Injury
      data, ergonomic assessments, staff questionnaires, and resident agitation
      checklists were used to evaluate the program in a 75 bed unit, with a similar
      unit acting as a comparison. The program resulted in an increased percentage of
      residents toileted regularly in the intervention unit, while aggressive incidents
      declined in both groups. Staff in the intervention unit reported a significantly
      lower perceived risk of injury to the head and neck than the comparison group.
      Although the program resulted in increased workload to manage multitasking,
      monitor an additional aspect of scheduled care, and perform more toileting
      transfers, overall risk of physical injury was reduced. The toileting program, a
      shift toward resident focused care, and enhanced agitation awareness combined to
      reduce resident handling injuries and resident agitation expressed as verbal
      behaviors or emotional upset, but not as physical behaviors. Clear communication,
      mentoring, and monitoring were important for successfully changing care
      practices.

PMID- 15508858
TI  - Evaluation of an environmental health education program: assessing changes in
      knowledge of health professionals.
AB  - Knowledge about environmental health is crucial for nurses so they can take into
      account both the living and occupational environments of clients during history
      taking and physical assessments. When focused on local environmental conditions
      and exposures, outreach educational programs on environmental health can result
      in a measurable increase of interest to learn and enhance the knowledge base of
      participants. Public health agencies and educational institutions should consider
      entering into partnerships to sponsor such professional development programs for
      nurses and other health professionals to promote the health of local populations.

PMID- 15508859
TI  - OSHA 101: an introduction to OSHA for the occupational health nurse.
AB  - The OSHA standards become easy to use with experience. Occupational health nurses
      who are unfamiliar with the standards are better served to use them as a
      reference, rather than attempting to read the entire document. Many of the
      standards have booklets published to assist users in understanding the
      information. These booklets are available within the publications link of the
      OSHA website. Occupational health nurses who have taken the initiative to gain
      knowledge about OSHA and to become fluent in navigating the OSHA standards soon
      discover that the ability to access the information contained in the standards
      quickly is a marketable skill. Employers depend on occupational health nurses to
      develop comprehensive programs that achieve the goal of injury prevention and
      also meet compliance requirements. The standards contain a wealth of information
      to do just that.

PMID- 15508860
TI  - Six tips for avoiding the spread of flu.

PMID- 15508861
TI  - Ocular health of overweight children.

PMID- 15508862
TI  - The future of optometric practice? The results of a survey of optometrists and
      optometry students.
AB  - BACKGROUND: There is an apparent increase in the number of private optometry
      practices that are closing due to a lack of interested buyers. We examined some
      of the factors that influence the market for optometry practices in a survey of
      practicing optometrists and third- and fourth-year optometry students. METHODS:
      Optometrists in six states, and students at four schools and colleges of
      optometry, completed a mailed or faxed survey regarding attitudes toward
      optometric practice, including fair/reasonable compensation for a new
      optometrist, the value of optometric practices, and preferred mode of practice on
      graduation. RESULTS: Doctors and students differed significantly in the amount of
      money they reported as fair/reasonable compensation for a recently graduated
      optometrist joining a practice. Comparing students to doctors in specific
      categories of compensation, students chose a higher fair/reasonable compensation
      compared to doctors. Students were more likely than doctors to choose >$70,000 as
      fair/reasonable compensation, while doctors were more likely than students to
      choose $40,000 to $69,000. Doctors tended to overvalue their practices for the
      purpose of selling the practice when using percentage of gross income as a
      valuation method. Students' choices for mode of practice changed dramatically
      from their ideal when taking their current financial situation into
      consideration. Students were more likely to choose corporate practice as their
      preferred practice mode when considering their current financial situation than
      when not restricted. CONCLUSIONS: There are many factors that affect the value
      and marketability of an optometric practice. In order to sell a practice, the
      owner must consider the effects of the needs and desires of recently graduated
      optometrists.

PMID- 15508863
TI  - Ocular manifestations of AIDS: new considerations for patients using highly
      active anti-retroviral therapy (HAART).
AB  - BACKGROUND: Highly active anti-retroviral therapy (HAART) effectively restores
      the immune system and lowers the viral load in patients with human
      immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). Since
      widespread use of HAART drugs began in 1996, many AIDS patients are living longer
      and enjoying a higher quality of life. The incidence of AIDS-related ophthalmic
      infections, such as cytomegalovirus (CMV) retinitis, have declined sharply. AIDS
      patients with CMV are less likely to experience necrotizing retinitis and retinal
      detachment, once the major causes of vision loss. HAART and immune recovery is
      now considered the preferred treatment for CMV retinitis. The role of immune
      recovery vitritis (IRV), a new manifestation of CMV retinitis, is now understood.
      In patients with pre-existing CMV retinitis who begin HAART the manifestations of
      an active immune system are seen, as the body is now able to fight the CMV
      infection. Incidence of Kaposi's sarcoma has declined by an estimated 87% and
      molluscum contagiosum is seen less frequently in those using HAART. With the
      clinical picture of ocular AIDS changing, the role of optometry in the management
      of AIDS patients is also changing.

PMID- 15508864
TI  - Test-retest reliability of the Saladin card.
AB  - BACKGROUND: Test-retest reliability is a measure of the confidence that results
      will be identical when the same patient is measured with an instrument in the
      same manner on more than one occasion. METHOD: Using the Saladin Near Point
      Balance Card--an instrument designed to test various near visual findings,
      including visual acuity, phorias, AC/A ratios, dynamic retinoscopy, fixation
      disparity, associated phorias, fixation disparity curves, as well as
      accommodative and vergence facilities--28 first- and second-year optometry
      students were evaluated on two occasions by one clinician, with the tests
      separated by approximately two weeks. Subjects were required to demonstrate 20/20
      distance visual acuity and at least 100 sec of arc stereopsis. A total of 38
      findings were compared, which included near horizontal and vertical phorias,
      associated phoria, and fixation disparity curves. Twenty-two findings were
      performed through the subjects' habitual prescription and the remaining findings
      were taken through the lens indicated by MEM retinoscopy. PURPOSE: The purpose of
      this study was to investigate whether the Saladin Near Point Balance Card had
      acceptable test-retest reliability. If reliability can be demonstrated, this
      instrument could be used in clinical situations to diagnose visual departures
      from normal. RESULTS: All but two of the 38 tests performed demonstrated
      acceptable test-retest reliability. Coefficients of repeatability and 95% limits
      of agreement were calculated. The Saladin Near Point Balance Card demonstrated
      acceptable test-retest reliability. CONCLUSION: Since it is light-weight,
      portable, easily and quickly administered, and reliable, the Saladin card can be
      used by clinicians who are performing screenings or examinations in non-clinical
      situations, such as nursing homes or schools.

PMID- 15508865
TI  - M-cell deficit and reading disability: a preliminary study of the effects of
      temporal vision-processing therapy.
AB  - BACKGROUND: This study examines the following questions: In moderately disabled
      readers, will temporal vision-processing therapy procedures that benefit reading
      comprehension, visual attention, and oculomotor skills ameliorate M-cell
      processing deficits as measured with coherent motion threshold testing? And will
      the results show a corresponding improvement in oral reading and verbal skills?
      METHOD: A sample of 16 moderately disabled readers, evaluated in a study
      completed 6 months earlier, were retested with another form of the Gates
      MacGinitie Reading Test. Each participant was additionally tested for coherent
      motion, oral reading, and word attack skills. During the succeeding 6 months,
      fifteen 45-minute therapy sessions were administered once a week (as the school
      schedule permitted). After completing 15 therapy sessions, the initial testing
      procedures were repeated. RESULTS: All four variables--namely, Gates-MacGinitie
      Reading Test, Coherent Motion Threshold Test, Gray Oral Reading Test, and
      Woodcock-Johnson Word Attack Test--revealed significant improvements after
      temporal vision therapy. Half of the 16 participants improved 2 or more years in
      reading comprehension, compared to no significant mean difference following the 6
      month "control period" before the onset of therapy. CONCLUSIONS: This research
      supports the value of rendering temporal vision therapy to children identified as
      moderately reading disabled (RD). The diagnostic procedures and the dynamic
      therapeutic techniques discussed in this article have not been previously used
      for the specific purpose of ameliorating an M-cell deficit. Improved temporal
      visual-processing skills and enhanced visual motion discrimination appear to have
      a salutary effect on magnocellular processing and reading comprehension in RD
      children with M-cell deficits.

PMID- 15508866
TI  - Faith-based optometry.

PMID- 15508868
TI  - Medicare learning online.

PMID- 15508867
TI  - An overview of the HIPAA Security Rule.

PMID- 15508869
TI  - HHS launches 'decade of health information technology'.

PMID- 15508870
TI  - Acute otitis media in children: current epidemiology, microbiology, clinical
      manifestations, and treatment.
AB  - An accurate differential diagnosis of AOM is essential for ensuring appropriate
      treatment, since overdiagnosis of disease is common and antibiotics are not
      indicated for otitis media with effusion. Although antibiotic therapy is required
      in only 20-30% of all AOM cases (high rate of spontaneous recovery), most of the
      patients are treated since this small proportion cannot be quickly and easily
      identified. The main determinant of the efficacy of antibiotics in AOM is the
      time that drug concentration at the site of infection exceeds the minimal
      inhibitory concentration for the pathogen. The major problems encountered in the
      antibiotic therapy of AOM are the tremendous increase in the resistance to
      antibiotics of its main pathogens and the lack of tight criteria in the selection
      of the appropriate antibiotic drugs for the treatment of this disease. The
      recently published Center for Disease Control and Prevention (CDC) guidelines for
      the treatment of AOM represent a major step forward in the rational approach to
      the management of this disease by establishing a clear hierarchy among the
      various therapeutic agents used in the treatment of simple and complicated AOM. A
      seven-valent pneumococcal conjugate vaccine recently licensed in the United
      States for universal immunization of infants <2 years has demonstrated efficacy
      for prevention of serotype-specific pneumococcal AOM.

PMID- 15508871
TI  - Clinical and electrophysiological studies of a family with probable X-linked
      dominant Charcot-Marie-Tooth neuropathy and ptosis.
AB  - BACKGROUND: The X-linked dominant Charcot-Marie-Tooth neuropathy (CMTX) is a
      hereditary motor and sensory neuropathy linked to a variety of mutations in the
      connexin32 (Cx32) gene. Clinical and genetic features of CMTX have not previously
      been reported in Taiwanese. METHODS: Clinical evaluations and
      electrophysiological studies were carried out on 25 family members of a Taiwanese
      family group. Molecular genetic analysis of the Cx32 gene was performed. A sural
      nerve biopsy was obtained from 1 patient. RESULTS: Nine patients had clinical
      features of X-linked dominant inheritance and a moderate Charcot-Marie-Tooth
      (CMT) neuropathy phenotype. Molecular genetic analysis showed no mutation of the
      Cx32 coding region, but revealed a G-to-A transition at position -215 of the
      nerve-specific promoter P2 of the Cx32 gene. Ptosis is 1 clinical manifestation
      of neuropathy in this probable CMTX family. Familial hyperthyroidism is an
      additional independent feature of the family. Electrophysiological and
      histological studies showed features of axonal neuropathy. Multimodality evoked
      potential studies revealed normal central motor and sensory conduction
      velocities. CONCLUSIONS: The presence of ptosis in this family illustrates the
      existence of clinical heterogeneity among related family members with CMTX
      similar to that in CMT of autosomal inheritance. Electrophysiological and
      histological findings revealed normal central conduction and axonal neuropathy.

PMID- 15508872
TI  - Neonatal group B streptococcal infection: a 7-year experience.
AB  - BACKGROUND: This retrospective study was designed to determine the trend of
      neonatal group B streptococcal (GBS) infection during the past 7 years at the
      Chang Gung Memorial Hospital of Kaohsiung, as well as to assess the risk factors,
      clinical features and patient outcomes. METHODS: Medical records of infants with
      neonatal GBS infection identified by positive results of cultures of sterile body
      fluid in our hospital from January 1996 through December 2002 were reviewed for
      demographic and clinical data. RESULTS: There were 33 infants with neonatal GBS
      infections during the past 7 years in our hospital. The number of patients
      increased from 1996 to 2001. Sixteen infants had early onset infections and 17
      infants had late onset infections. Of the nine patients with maternal risk
      factors in the early onset group, prolonged rupture of membranes (7, 44%) was
      most frequently encountered. Distressed respiratory sign (8, 50%) was the most
      common clinical presentation in early onset group, while fever >38 degrees C (17,
      100%) was the most common presentation in late-onset group. The mortality rates
      were 13% and 6% in early and late onset groups, respectively. Gestational age (p
      = 0.05) and pneumonia (p = 0.015) were two most important factors influencing the
      mortality rate. CONCLUSIONS: The number of GBS-infected infants seemed to have
      increased during the past 7 years in our hospital. Because the incidence of
      neonatal GBS infection and maternal colonization in Taiwan has not been
      collected, we could not determine the necessity of intrapartum chemoprophylaxis.
      Setting a comprehensive surveillance in Taiwan should be considered.

PMID- 15508873
TI  - Intra-abdominal cystic lymphangiomas in infancy and childhood.
AB  - BACKGROUND: Cystic lymphangiomas (CL) rarely present as intra-abdominal masses.
      Abdominal CL is often discussed in conjunction with mesenteric cysts; however,
      their histology, location and age of presentation differ significantly. In an
      attempt to establish a best diagnostic and treatment modality, we report our
      experience dealing with intra-abdominal CL during a 5-year period. METHODS:
      Between January 1998 and December 2003, 12 patients, 7 boys and 5 girls, with a
      diagnosis of CL were reviewed. Modes of clinical presentation, location of CL,
      methods of diagnosis, surgical intervention and histological examination were all
      analyzed. RESULTS: The ages of the 12 patients ranged from 8 days to 6 years.
      Eleven of the 12 patients were symptomatic with abdominal pain, abdominal
      distention or palpable mass , dysuria and severe acute abdominal pain mimicking
      appendicitis. Abdominal ultrasound was done preoperatively in all patients. At
      laparotomy, 5 CL were located in the omentum, 5 in the mesentery, and another 2
      in the retroperitoneum. All omental CL were completely excised without
      difficulty. CL removal required resection of both the cyst and intestine in 2
      patients. One of 2 retropritoneal CL was removed with small areas of the
      posterior wall of the cyst remaining on the inferior vena cava (IVC). There were
      no major postoperative complications, deaths, or recurrences in this series.
      CONCLUSIONS: Intra-abdominal CL are usually involved in young children and are
      usually symptomatic. A preoperative diagnosis is possible with ultrasound study.
      Complete excision of the cysts with or without intestinal resection is mandatory
      to prevent recurrence. The long-term prognosis is excellent.

PMID- 15508874
TI  - Concurrent chemoradiotherapy for unresectable thymic carcinoma.
AB  - BACKGROUND: Thymic carcinoma is a rare anterior mediastinal neoplasm. It is more
      invasive and has a poorer prognosis than ordinary thymoma. Complete curative
      resection is frequently impossible to achieve because of extensive invasion or
      metastasis at diagnosis. The role of systemic chemotherapy and the optimal
      regimen in thymic carcinoma remain uncertain. We report our experience with 16
      patients with unresectable thymic carcinoma who underwent concurrent
      chemoradiotherapy. METHODS: Between July 1989 and July 2003, 29 patients were
      diagnosed with unresectable thymic carcinoma at our hospital. Sixteen of the 29
      patients were treated with concurrent chemoradiotherapy. There were 10 men and 6
      women whose ages ranged from 45 to 66 years old. Chemotherapy regimens consisted
      of either (A) cisplatin plus 5-fluorouracil or (B) doxorubicin, cisplatin,
      vincristine and cyclophosphamide every 4 weeks for at least 2 cycles.
      Radiotherapy was given concurrently and ranged from 34.2 to 70 Gy. RESULTS: There
      were 4 (25.0%) patients with complete responses, 4 (25.0%) with partial
      responses, 6 (37.5%) with stable disease and 2 (12.5%) with progressive disease.
      The overall response rate was 50%. The median follow-up was 64 months, and the
      median survival was 82 months. The overall cumulative survival rates at 1, 2, 3,
      and 5 years were 93.8%, 81.3%, 74.5%, and 67.7%, respectively. The most common
      side effects were Grade I/II toxicity, including vomiting, fatigue, and
      esophagitis. All patients experienced radiation pneumonitis. No life-threatening
      side effects were noted. CONCLUSIONS: Concurrent chemoradiotherapy seems
      effective for unresectable thymic carcinoma. Our experience, although
      preliminary, is encouraging and merits conducting a randomized trial to determine
      the impact of concurrent chemoradiotherapy on unresectable thymic carcinoma.

PMID- 15508875
TI  - Combined surgery for intra-abdominal extra-urinary lesions in patients with renal
      and/or ureteral malignancies.
AB  - BACKGROUND: The standard treatment for patients with renal and/or ureteral
      malignancies is radical nephrectomy or nephroureterectomy. Frequently, intra
      abdominal extra-urinary lesions are noted preoperatively or intra-operatively in
      the gastrointestinal or gynecologic tract. We reviewed our experience with
      patients during an 11-year period. METHODS: From 1991 through 2001, 1059 patients
      underwent radical operations for renal and/or ureteral malignancies. Of these, 37
      patients had simultaneous intra-abdominal extra-urinary lesions preoperatively or
      intra-operatively and underwent surgery for these lesions at the same time as
      nephrectomy or nephroureterectomy. These patients were designated as group A and
      were compared with group B patients who underwent only radical urological
      surgery. RESULTS: The distributions of age, gender, preoperative evaluations, and
      histology did not differ significantly between the groups. The most common intra
      abdominal extra-urinary lesion was located in the gall bladder (51.4%). Although
      the patients with intra-abdominal extra-urinary lesions tended to have greater
      intra-operative blood loss (p = 0.8621), longer postoperative hospital stays (p =
      0.3414), and higher complication rates (p = 0.208) than those who did not, the
      differences were not significant. CONCLUSIONS: Given radical operations for renal
      and/or ureteral malignancies, synchronous surgery for intra-abdominal extra
      urinary lesions is feasible and safe with thorough postoperative care.

PMID- 15508876
TI  - Anterior cervical spinal surgery for multilevel cervical myelopathy.
AB  - BACKGROUND: In multilevel spinal cord compression caused by cervical spondylosis,
      surgeons face the choice of performing a posterior route as a laminectomy or
      laminoplasty, or an anterior route as multiple adjacent interbody decompressions
      or corpectomies. The anterior cervical operation is not considered by some
      clinicians because of concerns about complications and the complexity of
      multilevel anterior cervical surgery. METHODS: In this retrospective study, 14
      patients with multilevel cervical spondylosis who were operated on via an
      anterior route were enrolled to evaluate the complexity, safety, and clinical
      results. The collected parameters were operation time, blood loss, hospital days,
      and early and late complications for evaluating the operative complexity,
      radiographic follow-up for evaluating fusion, graft problems, implants problems,
      and the recovery rate using the Japanese Orthopaedic Association score (JOA
      score) for evaluating the operative results. RESULTS: The mean operation time was
      363.4 min, and blood loss was 431.4 ml. An early complication was noted in 1
      patient with combined deep vein thrombosis and a pulmonary embolism. Late
      complications were screw breakage in 1 patient and screw loosening in 5 patients.
      The mean duration of follow-up was 21.9 months. The mean recovery rate of the JOA
      score was 38.8% postoperatively and 51.9% at the final follow-up. The fusion rate
      was 100% in this series. CONCLUSIONS: Anterior cervical decompression and fusion
      for multilevel stenosis requires a longer operation time than posterior
      procedures; however, the clinical results are satisfactory.

PMID- 15508877
TI  - Treatment of infected tibial nonunion with tobramycin-impregnated calcium
      sulfate: report of two cases.
AB  - The treatment of infected tibial nonunion usually includes a staged
      reconstruction protocol. We present 2 patients with tibial nonunion and plate
      loosening with oxacillin-resistant Staphylococcus aureus infection. The patients
      were treated using the removal of the plate, radical debridement, and
      implantation of gentamycin-impregnated cement beads during the first stage.
      During the second stage, plate fixation was performed and tobramycin-impregnated
      calcium sulfate (Osteoset T) was used as a bone graft substitute. Neither an
      autogenous bone graft nor an allograft was used. At 3 years of follow-up, each
      tibia showed good union, and there was no recurrence of infection. We consider
      tobramycin-impregnated calcium sulfate to be an alternative method of bone
      grafting to treat infected tibial nonunion.

PMID- 15508878
TI  - Congenital short bowel syndrome with malrotation.
AB  - Congenital short bowel syndrome (SBS) associated with malrotation and
      malabsorption is a very rare condition. We report on an infant girl with
      congenital SBS associated with malrotation and malabsorption. No polyhydraminos
      was noted during the regular prenatal examination. Protracted postnatal
      postprandial vomiting with progressive failure to thrive was noted. A laparotomy
      showed the small bowel was only about 20 cm in length. She eventually survived
      with short-term parenteral nutrition and use of oral L-glutamine supplementation.
      To our knowledge, this might be the shortest length of bowel loop ever reported.
      Currently, she is 15 months of age with a body weight of about 7 kg and good
      development.

PMID- 15508879
TI  - 49, XXXXY syndrome.
AB  - 49, XXXXY syndrome is a rare sex chromosomal disorder. A 5-month-old boy had
      failure to thrive and multiple congenital anomalies including microcephaly,
      facial dysmorphism (hypertelorism, megacornea, cleft palate, and micrognathia),
      obvious heart murmur, umbilical hernia, microphallus, and mild clenched hands.
      Chromosomal studies via techniques of G-banding and fluorescence in situ
      hybridization showed the constitution to be 47, XXXXY in all cells.
      Ventriculomegaly and congenital cardiac defects (patent ductus arteriosus, atrial
      septal defect, and peripheral pulmonary stenosis) were noted. He has severe
      atopic dermatitis with high IgE levels and psychomotor retardation. After heart
      surgery and nutritional support, he has better growth and the rehabilitation
      program is continuing.

PMID- 15508880
TI  - Idiopathic subconjunctival abscess.
AB  - Subconjunctival abscess is a relatively rare cause of ocular infection. It is
      usually associated with predisposing factors such as previous trauma or surgery.
      We report a case of subconjunctival abscess in a 61-year-old woman with no known
      risk factors. The subconjunctival abscess resolved completely after surgical
      excision and treatment with topical ciprofloxacin. The final vision preserved
      20/20.

PMID- 15508881
TI  - Mental imagery: the language of spirit.

PMID- 15508882
TI  - "Never the twain shall meet": spirituality or psychotherapy?

PMID- 15508883
TI  - Psychosocial factors in heart disease: a process model.

PMID- 15508884
TI  - The fog of war.

PMID- 15508885
TI  - HIV/AIDS, peacekeeping and conflict crises in Africa.
AB  - This article investigates the impact of the spread of HIV/AIDS on the African
      military and its ability to act as an effective instrument of conflict resolution
      in the continent. The capacity of African militaries is particularly important at
      a time when major powers are reluctant to engage in greater peacekeeping
      operations in the region. The widespread prevalence of HIV among military
      personnel threatens political and social stability more generally, and this study
      focuses on the link between peacekeeping and the disease. It considers how HIV
      positive soldiers act as a vector in communities where they are deployed, and how
      soldiers deployed in locations with a high prevalence rate of HIV/AIDS may spread
      the disease in their home communities upon return. Possible recommendations on
      how to tackle HIV/AIDS prevention efforts with the aid of peacekeepers are
      offered.

PMID- 15508886
TI  - Is Gulf War Syndrome really a mystery?
AB  - Since the end of the 1991 Gulf War about 20,000 United States veterans and
      similar proportions of troops from other allied contingents have been affected by
      a variety of symptoms which have collectively become known as 'Gulf War
      Syndrome'. Similar symptoms have been reported in Iraqi civilians including
      children. Despite extensive investigations no agreement has been reached on
      whether there is an underlying cause or causes. In this article, the principal
      features of the illness are summarised and some of the proposed causes discussed.
      It is proposed that the common cause is the toxic smoke from incomplete
      combustion of oil from burning wells, and this hypothesis is related to the known
      toxicology of two likely combustion products, nitric oxide and carbon monoxide.
      The effect of this proposal on possible investigations and treatment is
      considered.

PMID- 15508887
TI  - Establishing the possible radiogenicity of morbidity and mortality from
      participation in UK nuclear weapons development.
AB  - To succeed in compensation claims for radiogenic injuries induced by their
      participation in the United Kingdom's atomic and nuclear weapons tests of the
      1950s and 1960s, the 22,000 nuclear test veterans will have to satisfy Hill's
      Principles of Causation. Although they are blocked by legal restraints from suing
      the Crown, the evidential case for the veterans has been strengthening in recent
      years to a point where it would probably succeed in a UK court of law. The delay
      in mounting such a case has worked in favour of the veterans; if the legal
      constraints are removed, their chances of success are greater than if they had
      gone into court a decade ago. The article examines the evidence in support of
      their claims in relation to each of Hill's Principles.

PMID- 15508888
TI  - Peace through health I: development and use of a working model.
AB  - Peace through Health (PtH) is an evolving academic discipline that explores how
      health interventions may contribute to peace in actual and potential war zones
      and situations of conflict. This article is an attempt to define the scope of PtH
      activities, to develop a framework for groups and individuals to conceptualise
      their role in peace work and to develop clearly definable goals for evaluation.
      The use of a new model of 'Peace through Health' work is explored. A
      demonstration of how this model could help guide actions of organisations working
      for peace in current and potential war zones is undertaken. In particular, the
      work of International Physicians for the Prevention of Nuclear War and medical
      war prevention work in Iraq since 1990 is discussed. It is felt that such a model
      might be used to classify and better direct medical peace work to areas of
      expertise.

PMID- 15508889
TI  - Peace through health II: a framework for medical student education.
AB  - The world's first university course in Peace through Health (PtH) recently
      finished at McMaster University, Hamilton, Canada. Medical students and academic
      staff in Canada and Europe have expressed interest in developing this course for
      other medical schools. Seven medical students were selected to do an unofficial
      'audit' in return for 'in kind' work, developing the course materials for the web
      and adaptation to the medical curriculum. This article sets out the goals and
      structure of the course as a guide for similar teaching models.

PMID- 15508890
TI  - IPPNW's campaign for a nuclear-weapons-free century: South Asia dialogues and the
      Non-proliferation Treaty PrepCom.

PMID- 15508891
TI  - Introduction. Responses to weak acids, alkalinisation, biocides, UV irradiation,
      and toxic metal ions.

PMID- 15508892
TI  - Weak organic acids: a panoply of effects on bacteria.
AB  - Weak organic acids have been used for centuries to preserve foods, but only
      recently has the possible mechanism for bacterial growth inhibition been
      investigated. Although the lowering of internal pH was favored as the cause of
      growth inhibition, the emphasis has shifted to the anion and its specificity.
      There are a number of applications of weak organic acids to foods and in the food
      industry be they pre- or postharvest, However, there is concern that the ability
      of foodborne pathogens to adapt to these acids may allow longer survival in these
      commodities and also to better survive transit through the gastric acid barrier
      of the stomach. Genomic and proteomic approaches have been applied to the
      identification of genes and proteins that may allow prokaryotes to cope with
      organic acid stress. These technologies in combination with genetic approaches
      may provide better identification of genes essential for survival to organic
      acids. These acids may have other roles: they can induce phenotypic antibiotic
      resistance, and the high concentrations of these acids in the colon may signal a
      relationship to diet, colonic microflora, and human health.

PMID- 15508893
TI  - Bacterial responses to alkaline stress.
AB  - Studies of bacterial adaptation to alkaline pH have been less extensive to date
      compared with those of acidic pH. Recent development of novel methods for global
      analysis of gene expression under various conditions revealed that many genes
      were induced at high pH. These data led us to question why so many genes are
      required for adaptation to alkaline pH. The internal pH of bacteria growing at
      extremely high pH remains unclear because the methods for measuring interior
      acidic deltapH developed to date are not so accurate, but it is generally
      accepted that cytoplasmic pH increases with medium alkalization, although the
      increase is lower than that of the change in medium pH. Therefore, activities of
      enzymes working in neutral cytoplasm may decrease with cytoplasmic alkalization
      under extreme alkaline conditions. Based on these findings, we propose in this
      article that genes whose products have an optimum activity at high pH are induced
      under alkaline stress to compensate for the decrease in activities of systems
      functioning at neutral pH.

PMID- 15508894
TI  - Bacterial outer membrane and cell wall penetration and cell destruction by
      polluting chemical agents and physical conditions.
AB  - In the environment, bacteria and other microorganisms are subjected to a variety
      of constantly changing chemical and physical agencies. Chemical ones include
      antimicrobial compounds (both biocides and antibiotics), pollutants, drugs,
      cosmetic and pharmaceutical ingredients and pesticides. The physical agents
      include desiccation and drying, osmotic pressure, hydrostatic pressure,
      temperature and pH changes and radiations (ultraviolet, sunlight, ionizing).
      Bacteria must thus adapt to survive these inimicable conditions. Organisms such
      as bacterial spores usually survive, whereas other types of microorganisms may be
      much more susceptible. Depending on the type of organism, the bacterial cell
      wall, outer membrane or the spore outer layers may act as permeability barriers
      to the intracellular uptake of antibiotics and biocides. Some antibacterial
      agents interact with, and damage or modify, the outer components. Physical
      agencies are known to damage the cytoplasmic membrane or to produce alterations
      in DNA or proteins or enzymes. Nevertheless, significant damage to the cell wall
      or outer membrane may also occur. Four types of organisms are considered: cocci,
      mycobactria, Gram-negative bacteria and bacterial spores. The nature of the
      damage inflicted on, or in some cases prevented by, their outer cell layers is
      discussed for each type of organism.

PMID- 15508895
TI  - UV radiation-induced enterobacterial responses, other processes that influence UV
      tolerance and likely environmental significance.
AB  - The ability of enterobacteria to become UV-tolerant is important because such
      tolerance may enable organisms to resist irradiation in the environment, in water
      treatment, in shell-fish, in stages of food processing, and at locations in the
      domestic, commercial and hospital environment The mechanism for regulation of
      tolerance induction and SOS response induction has been studied for many years,
      and is well understood, except for the early stages of induction. Such early
      stages, namely sensing of the stimulus (UV irradiation) and the way in which such
      sensing leads to signal production, have until now been poorly understood. The
      claim has been made that DNA is the sensor and that either damage to DNA or
      production of SS regions in DNA (following interaction of UV with DNA) triggers
      the signal that sets in train RecA activation and other stages of tolerance
      induction. This claimed induction mechanism is a "classical" one in the sense
      that it involves intracellular sensing (by DNA) of the stressing stimulus (UV),
      and production of an intracellular signalling molecule. It is not, however,
      firmly established as the mechanism for initiation of UV tolerance induction and
      SOS response induction. The results reviewed here give firm evidence for a
      different and unique mechanism for sensing of UV and production of the signal.
      These results establish without doubt that, for UV tolerance induction, the UV
      sensor is an extracellular protein, which is a UV tolerance-specific
      extracellular sensing component (ESC). This component is formed by unstressed
      cells and on interacting with the stimulus (UV) in the medium, is converted to
      the tolerance induction signalling molecule, which is a UV tolerance-specific
      extracellular induction component (EIC). It is this extracellular signal which
      interacts with the sensitive organisms and triggers tolerance induction. This
      pair of extracellular components (ECs) may offer the only means of switching-on
      such tolerance induction; certainly they offer the only known way for early
      warning to be given of impending UV challenge. Thus, the EIC can diffuse from a
      region of UV stress to a stress-free region and there warn organisms of impending
      stress and prepare them to resist it. As indicated here, UV irradiation not only
      induces UV tolerance, but also switches-on acid tolerance, alkali tolerance and
      thermotolerance responses. The fact that all three responses involve ESC/EIC
      pairs strongly supports the view that functioning of such EC pairs form the
      major, if not the only, means for UV tolerance induction. The UV tolerance
      specific ESC can detect other stresses and becomes activated, leading to cross
      tolerance responses. Of particular interest, this ESC acts as a biological
      thermometer, detecting increases in temperature, such increases leading to
      gradually increasing formation of the EIC and, accordingly, gradual increases in
      UV tolerance. This UV tolerance-specific ESC can also detect other stresses e.g.
      acting as a pH sensor. In all cases, on activation, the EIC formed (from this
      specific ESC) only induces UV tolerance. It is proposed that the interaction of
      EICs with stress-sensitive organisms should be examined, and it is suggested that
      such EICs may, directly or indirectly, interact with and activate the same stress
      response regulators as are used to detect internal stressors and which, on
      activation, also trigger the switching-on of stress responses. For example, EICs
      either a in a protonated or oxidised state (formed by activation of ESCs by H+ or
      H2O2) or b produced by irradiation, may lead to protonation or oxidation or other
      forms of activation of the appropriate regulator (e.g. Fur or OxyR or RecA etc),
      leading to response induction.

PMID- 15508896
TI  - An evaluation of GAEL, the Global Alliance for the Elimination of Leprosy.

PMID- 15508897
TI  - What lessons can we learn from the evaluation of GAEL?

PMID- 15508898
TI  - Comments on the report entitled 'Independent evaluation of the Global Alliance
      for the Elimination of Leprosy'.

PMID- 15508899
TI  - Measuring impairment caused by leprosy: inter-tester reliability of the WHO
      disability grading system.
AB  - This paper reports the results of a study on the inter-tester reliability of the
      WHO disability grading system. The WHO disability grading system is the most
      frequently used method of grading impairment in leprosy patients. With this
      method, a grade of 0-2 is assigned to each of six individual body sites (both
      eyes, hands and feet). The maximum grade of any of these sites is used as an
      overall indicator of the person's impairment status. To date, the WHO disability
      grading scale has not been subjected to reliability testing. The reliability of
      the grading system depends on the operational definitions of the grades, the way
      the tester interprets these definitions and the skill of the tester. It is
      therefore important that the definitions are unambiguous and leave as little room
      as possible for multiple interpretations. Three testers with varying degrees of
      experience did paired assessments on a total of 150 leprosy patients in the
      Leprosy Mission Hospital Purulia, India, using recently published operational
      definitions of the WHO disability grades. For every patient, they determined the
      maximum grade (minimum 0, maximum 2), and calculated the impairment sum-score
      (EHF score), adding up the six grades for eyes, hands and feet (minimum 0,
      maximum 12). The weighted Kappa statistic (Kw) was used as the coefficient of
      inter-tester reliability. A kappa of 0 represents agreement no better than
      chance, and 1.0 complete (chance-corrected) agreement. Kw values of > or = 0.80
      are considered very good and adequate for monitoring and research. Weighted Kappa
      analysis yielded a reliability coefficient of 0.89 (95%CI 0.84-0.94) for the
      maximum grade and a Kw of 0.97 (95%CI 0.96-0.98) for the EHF score. We concluded
      that, when using standard operational definitions, the WHO disability grading
      system can be used reliably in the hands of both experienced and inexperienced
      testers, provided adequate training has been given. Reliability should be
      evaluated further in a field setting, when used by primary health care workers.
      It is recommended that the 'WHO disability grading' be renamed 'WHO impairment
      grading', using the terminology as defined by the International Classification of
      Functioning, Disability and Health (ICF).

PMID- 15508900
TI  - Neural pathology in leprosy during treatment and surveillance.
AB  - The histological findings of 22 patients with neuritis, 14 developing pain,
      tenderness and swelling during treatment and 8 during surveillance are presented
      in this study. Seven patients' biopsies showed macrophage type and 14 had
      epithelioid cell type of granulomas. All biopsies showed evidence of active
      disease, except for two patients with macrophage granulomas where some regressive
      changes were evident. One biopsy showed fibrosis with lymphocytic infiltration.
      The histology of epithelioid cell granulomas had varied histopathological
      presentations ranging from non-reacting BT to those with severe type I reaction
      with caseation necrosis, liquefaction and calcification. Two macrophage
      granulomas showed partial regression though there was neuritis clinically and
      features of ENL in the biopsy sections. One biopsy showed histoid changes. All
      the biopsies showed similar histopathological features irrespective of whether
      neuritis appeared during treatment or surveillance. The features of reaction were
      severe in nerves, probably due to the adjuvant nature of lipid and myelin in the
      nerve tissue. The histopathological features of nerve biopsies from patients
      under surveillance appeared to be ongoing active disease rather than relapse.

PMID- 15508901
TI  - Clinical, electroneuromyographic and morphological studies of pure neural leprosy
      in a Brazilian referral centre.
AB  - Nineteen patients with pure neural leprosy were analysed with clinical
      examination, electroneuromyography and histopathology of nerve biopsies. Clinical
      examination showed sensory loss (78.9%), paresis (78.9%), nerve enlargement
      (68.4%) and nerve pain (42.1%). Electroneuromyographic study revealed an axonal
      pattern in 18 patients (94.7%) and a demyelinating pattern in one (0.5%).
      Mononeuropathy multiplex was the most frequent presentation (78.9%), followed by
      mononeuropathy simplex (10.5%) and polyneuropathy (10.5%). The histopathological
      study showed the presence of inflammatory infiltrate composed of epithelioid
      granuloma (42.1%), mononuclear infiltrate (36.8%) or macrophages positive for
      bacilli (21%). Fibrosis was present in 78.9% of the biopsies. Examination of
      semithin sections revealed, besides inflammatory infiltrate, myelinated fibre
      loss (94.7%), remyelination (42%), axonal degeneration (10%) as well as
      regeneration (31.5%). Based on these results, the pathogenesis of leprosy
      neuropathy in this group of patients is briefly discussed.

PMID- 15508902
TI  - Management of 34 chronic heel sinuses in leprosy, using a modification of a local
      rotation flap in Kolkata, India.
AB  - We have seen 55 trophic ulcers of the heel in 2 years in our hospital, between
      March 2000 and February 2002. Thirty-four were chronic heel sinuses, six cases of
      multiple sinuses and 28 cases of single sinus of the plantar aspect of the heel.
      All these cases were treated by excision of the sinus, paring the prominence of
      the calcaneum, or excision of the cavity within the calcaneum and coverage by a
      rotation flap or a modification of this flap. Over the past 6 years, we have
      evolved a modification of a rotation flap that requires a fusiform incision to
      excise the sinus, and a curved incision for the flap extending through the instep
      and the non-weight bearing heel. The fusiform excision, rather than the
      traditional triangulation, causes the flap to partly transpose rather than rotate
      completely. The flap is raised superficial to the plantar aponeurosis, exposing
      the aponeurosis from mid-sole to the heel. It is a modification of a rotation
      flap. The scarring over the weight-bearing sole is minimal, restricted only to
      the incision necessary for the excision of the heel sinus and this is its main
      advantage. Twenty-one of the 34 cases healed without complications. Thirteen
      cases had complications, of which six were treated non-operatively and seven
      required either a redo of the flap or another flap cover.

PMID- 15508903
TI  - Utility of serodiagnostic tests for leprosy: a study in an endemic population in
      South India.
AB  - In order to evaluate the usefulness of natural disaccharide (PGL1) and 35 kDa
      antigens based serology in diagnosis of leprosy and in detecting high risk groups
      for leprosy, this study was conducted in an endemic population in South India.
      Out of 3346 cases and their households and neighbouring household contacts, serum
      samples from 2994 and 2875 individuals were screened for antibodies against PGL1
      and 35kDa antigens respectively. While the overall positivity for contacts and
      leprosy cases was 3.3% for PGL1 antibody, the positivity for 35 kDa antibody was
      6.3%. The positivity for contact population was 2.7% and 5.4% for PGL1 and 35 kDa
      antibodies, respectively. Lepromatous and borderline lepromatous patients showed
      positivity of 35.1% for PGL1 antibody and 45.7% for 35 kDa antibody. Follow-up of
      contacts showed that the majority (>90%) remained seronegative for both the
      antibodies and most of the new cases emerged from the seronegative group. The
      study clearly indicates that specific serological assays are not sensitive enough
      for application, both for diagnosis and for identifying any individual at risk
      for leprosy in the south Indian endemic population.

PMID- 15508904
TI  - Serial measurement of serum cytokines, cytokine receptors and neopterin in
      leprosy patients with reversal reactions.
AB  - Serum levels of cytokines (IL-4, IL-5, IFN-gamma, TNF-alpha), cytokine receptors
      (TNFR I and II) and one monokine (neopterin) were estimated in seven leprosy
      patients to establish disease associated markers for reversal reactions (RR).
      Sera were collected at diagnosis of leprosy, at the onset of reversal reaction
      and at different time points during and at the end of prednisone treatment of
      reactions. It was expected that the serum cytokine and monokine profile before
      and at different time points during reactions would provide guidelines for the
      diagnosis and monitoring of reversal reactions in leprosy. The cytokines and
      cytokine receptors were measured by ELISA, whereas a radioimmunoassay was used
      for neopterin measurement. Six of the seven patients showed increased levels of
      neopterin either at the onset of RR or 1 month thereafter, and levels declined on
      prednisone treatment to that seen at the time of diagnosis without reactions. No
      consistent disease associated cytokine profile was observed in these patients.
      Interestingly, serum TNF-alpha levels were increased in the same patients even
      after completion of prednisone treatment, indicating ongoing immune activity. In
      conclusion, this study demonstrates that despite cytokines levels in leprosy
      serum being inconsistent in relation to reversal reactions, serum neopterin
      measurement appears to be an useful biomarker in monitoring RR patients during
      corticosteroid therapy.

PMID- 15508905
TI  - Mycobacterium leprae infection and serum lactoferrin levels.
AB  - Serum lactoferrin level, using competitive enzyme linked immunosorbent assay
      (ELISA) method, was estimated in 298 leprosy patients admitted into the hospital
      and attending the out-patient department of the Schieffelin Leprosy Research and
      Training Center. Serum from an equal number of non-leprosy individuals served as
      control. Mean (SD) of serum lactoferrin in non-leprosy individuals was 0.277 (0
      092) microg/ml while in leprosy patients it was 0.494 (0.394) microg/ml, the
      difference being significant (P=0.0001). Serum lactoferrin levels were not
      significantly associated with type 2 reactions (P=0.613). Serum lactoferrin was
      significantly associated with age (P = 0.006), duration of the disease
      (P=0.0001), DDS monotherapy (P =0.007), deformity (P= 0.005), average bacterial
      index (BI) (P=0.01) and smear positivity (P=0.0001), orbicularis oculi weakness
      (P= 0.001), lagophthalmos (P = 0.002), corneal opacity (P = 0.001) and cataract
      (P=0.004) in simple regression analysis. All these variables, with the exception
      of smear positivity (P=0.019), lost their significance (P>0.05) when analysed
      using multiple regression. Serum lactoferrin showed poor association with type 1
      (P = 0.286) and type II reactions (P = 0.613) and iridocyclitis (P = 0.207). We
      conclude that serum lactoferrin is strongly and inversely associated with
      increasing BI but does not show significant association with type 2 reactions.

PMID- 15508906
TI  - What epidemiologic studies tell us about the relationship between fruit and
      vegetable consumption and body weight.
AB  - Clinical evidence shows that combining advice to increase fruit and vegetable
      consumption with caloric restriction is an effective strategy for weight
      management. The purpose of this review is to evaluate epidemiologic evidence to
      determine whether it supports an association between fruit and/or vegetable
      consumption and body weight. Few studies have been designed to specifically
      address this issue, and those that are available vary in methodology and offer
      inconsistent results. We make recommendations on how to strengthen future studies
      so that the influence of fruit and vegetable consumption on body weight in free
      living individuals is better understood.

PMID- 15508907
TI  - Phytochemical research using accelerator mass spectrometry.
AB  - Vegetables and fruits provide an array of microchemicals in the form of vitamins
      and secondary metabolites (phytochemicals) that may lower the risk of chronic
      disease. Tracing these phytochemicals at physiologic concentrations has been
      hindered by a lack of quantitative sensitivity for chemically equivalent tracers
      that could be used safely in healthy people. Accelerator mass spectrometry is a
      relatively new technique that provides the necessary sensitivity (in attomoles)
      and measurement precision (<3%) towards 14C-labeled phytochemicals for detailed
      kinetic studies in humans at dietary levels.

PMID- 15508908
TI  - Insulin resistance and obesity: resistin, a hormone secreted by adipose tissue.
AB  - A newly discovered hormone named adipocyte-secreted factor, or resistin, is
      secreted by adipocytes in mice. Expression of resistin is low during food
      deprivation and in diabetes, and increased greatly during refeeding and insulin
      treatment. It is found in serum in mice and humans, and is greatly increased in
      obesity. Resistin inhibits adipocyte differentiation and may function as a
      feedback regulator of adipogenesis. Administration of resistin to mice resulted
      in increased glucose production and blood glucose levels. Therefore, resistin
      also functions as a regulator of glucose homeostasis and a physiologic antagonist
      to hepatic insulin action.

PMID- 15508909
TI  - Central obesity and elevated liver enzymes.
AB  - Nonalcoholic fatty liver disease is commonly associated with obesity, a growing
      epidemic worldwide. A new large, population-based investigation has shown a
      statistically significant association between central adiposity and elevated
      liver enzymes. This finding adds to the growing research specifically linking
      central adiposity, and more specifically, visceral adiposity, with adverse health
      effects.

PMID- 15508910
TI  - History and classification of "myoclonic" epilepsies: from seizures to syndromes
      to diseases.

PMID- 15508911
TI  - Ontogeny of the reticular formation: its possible relation to the myoclonic
      epilepsies.

PMID- 15508912
TI  - Pathophysiology of myoclonic epilepsies.

PMID- 15508913
TI  - Progressive myoclonus epilepsies: EPM1, EPM2A, EPM2B.

PMID- 15508914
TI  - Myoclonic status in nonprogressive encephalopathies.

PMID- 15508915
TI  - Severe myoclonic epilepsy in infancy: Dravet syndrome.

PMID- 15508916
TI  - Severe myoclonic epilepsy in infancy: clinical analysis and relation to SCN1A
      mutations in a Japanese cohort.

PMID- 15508917
TI  - Myoclonic seizures in the context of generalized epilepsy with febrile seizures
      plus (GEFS+).

PMID- 15508918
TI  - Benign myoclonic epilepsy in infancy.

PMID- 15508919
TI  - Autosomal recessive benign myoclonic epilepsy of infancy.

PMID- 15508920
TI  - Myoclonic-astatic epilepsy of early childhood--definition, course, nosography,
      and genetics.

PMID- 15508921
TI  - Idiopathic myoclonic-astatic epilepsy of early childhood--nosology based on
      electrophysiologic and long-term follow-up study of patients.

PMID- 15508922
TI  - Myoclonic absences: the seizure and the syndrome.

PMID- 15508923
TI  - Eyelid myoclonia and absence.

PMID- 15508924
TI  - Childhood absence epilepsy evolving to juvenile myoclonic epilepsy:
      electroclinical and genetic features.

PMID- 15508925
TI  - Photosensitivity: genetics and clinical significance.

PMID- 15508926
TI  - Familial juvenile myoclonic epilepsy.

PMID- 15508927
TI  - Genetics of juvenile myoclonic epilepsy: faulty components and faulty wiring?

PMID- 15508928
TI  - Autosomal dominant juvenile myoclonic epilepsy and GABRA1.

PMID- 15508929
TI  - CLCN2 and idiopathic generalized epilepsy.

PMID- 15508930
TI  - Autosomal dominant cortical myoclonus and epilepsy (ADCME) with linkage to
      chromosome 2p11.1-q12.2.

PMID- 15508931
TI  - Familial adult myoclonic epilepsy (FAME).

PMID- 15508932
TI  - Treatment of myoclonic epilepsies in infancy and early childhood.

PMID- 15508933
TI  - Ketogenic diet in patients with Dravet syndrome and myoclonic epilepsies in
      infancy and early childhood.

PMID- 15508934
TI  - Treatment of myoclonic epilepsies of childhood, adolescence, and adulthood.

PMID- 15508935
TI  - The clinical presentation of lysosomal storage disorders.
AB  - Lysosomal storage disorders (LSDs) are present from conception and produce a
      clinical phenotype that evolves with time. The introduction of new therapies has
      made early diagnosis a priority. Clues to the clinical diagnosis of a LSD can be
      found in the tempo of the illness especially if the central nervous system is
      involved. Loss of a previously acquired skill (regression) is very characteristic
      of this group of disorders. Other clinical clues can include a dysmorphic
      appearance or the presence of characteristic skeletal involvement (dysostosis
      multiplex), but in some disorders such as Pompe disease or Krabbe disease, these
      do not occur. The approach to diagnosis has to involve "screening" as there can
      be considerable overlap in clinical presentation (e.g. Gaucher disease and
      Niemann-Pick B). Both urine and blood testing are necessary and the majority of
      diagnoses can now be confirmed at a molecular level. Prenatal diagnosis is
      possible for all.

PMID- 15508936
TI  - Role of diffusion-weighted imaging and proton MR spectroscopy in distinguishing
      between pyogenic brain abscess and necrotic brain tumor.
AB  - Brain abscesses and brain tumors may have similar clinical presentations. For
      example, only 50% brain abscess patients have fever, which could be masked by
      corticosteroid therapy. Also, the differential diagnosis of brain abscesses
      versus cystic or necrotic tumors may be difficult based on computed tomography
      (CT) or magnetic resonance (MR) imaging findings. However, the strategies of
      management for abscess and neoplasm are very different, and it is especially
      imperative to have a correct diagnosis before any surgical intervention of cystic
      brain lesions. The MR special techniques, e.g. diffusion-weighted imaging (DWI)
      and proton (1H) MR spectroscopy, are useful as additional diagnostic modalities
      for differentiating brain abscesses from cystic or necrotic brain tumors. DWI
      shows high signal intensity in most cases of pyogenic abscesses and low signal
      intensity in most cases of cystic or necrotic tumors. MR spectroscopy shows
      characteristic metabolites in pyogenic abscesses, distinct from those in cystic
      or necrotic tumors.

PMID- 15508937
TI  - Sensory nerve conduction studies of the superficial peroneal nerve in L5
      radiculopathy.
AB  - BACKGROUND: Theoretically, sensory nerve action potential (SNAP) of the
      superficial peroneal nerve (SPN) should be preserved when L5 roots are damaged.
      Previous study indicated that SNAP of SPN was lost or reduced in amplitude in
      patiens with L5 radiculopathy. To address this issue, this study compared results
      of SPN sensory conduction studies between healthy subjects and patients with L5
      radiculopathy. METHODS: Ninety-four healthy subjects were enrolled and assigned
      to two age groups: group I (< or = 60 years, n=61) and group II (> 60 years,
      n=33). Forty-one patients with unilateral L5 radiculopathy were enrolled by our
      electrodiagnostic laboratory between July 2000 and July 2003 and assigned to two
      age groups: 60 years or below (n=19) and above 60 years (n=22). RESULTS: SPN
      response was found to be abnormal in only 1.6% of group I healthy subjects, but
      absent or abnormal SPN response was noted in 21.1% of patients with L5
      radiculopathy of the same age group (p=0.01). However, a greater proportion of
      (27.3%) our healthy subjects above 60 years had abnormal SPN responses. This
      proportion was similar to that of patients with L5 radiculopathy and abnormal SPN
      response (31.8%) (p=0.72). CONCLUSIONS: SPN sensory responses are reliably
      obtained in most healthy subjects under 60 years of age. Absence of SNAP or
      reduced SNAP amplitude of SPN on the side of their lesions did not necessarily
      exclude the diagnosis of L5 radiculopathy in the patients under 60 years of age.

PMID- 15508938
TI  - Clinical findings of intracranial vertebral artery disease using magnetic
      resonance angiography.
AB  - The vertebral artery lesion has a variety of clinical characteristics. We sought
      to clarify the clinical patterns and the location of the intracranial vertebral
      artery (ICVA) diseases according to analyses of images obtained using magnetic
      resonance angiography (MRA). We studied vascular lesions, risk factors, symptoms,
      signs, and outcomes in 35 patients with ICVA disease (3 had bilateral occlusion;
      9, unilateral occlusion; 6, bilateral stenosis; and 17, unilateral stenosis). The
      most common site of unilateral and bilateral lesions was the distal ICVA after
      the origin of posterior inferior cerebellar artery (PICA). We found accompanying
      basilar artery disease in 28.6% of patients with unilateral and bilateral ICVA
      disease. The majority of the ICVA lesions were associated with internal carotid
      arteries disease (48.8%). The common vascular risk factors were hypertension
      (71%), diabetes mellitus (34%), hyperlipidemia (31%), smoking (29%), and coronary
      artery disease (23%). Eighteen patients (51.4%) had transient ischemic attacks
      (TIAs) only, 10 patients (28.6%) had TIAs before stroke, and 5 patients (14.3%)
      had strokes without TIAs. Most patients (80%) with TIAs, with or without stroke,
      had multiple episodes. Vertigo or dizziness, ataxia, limbs weakness and abnormal
      gait were the common symptoms and signs. At 6 months follow-up, 66.7% patients
      had no symptoms or only slight symptoms that caused no disability. Our data
      showed (1) the usual location of ICVA disease (occlusion or severe stenosis) was
      distal to PICA, especially near the vertebrobasilar junction; (2) the risk
      factors were hypertension, diabetes mellitus, hyperlipidemia, smoking, and
      coronary artery disease; (3) patients with ICVA disease had a high frequency of
      accompanying internal carotid, middle cerebral, or basilar artery disease; (4)
      vertigo or dizziness, and ataxia were the common symptoms and signs; (5) TIA was
      the most common clinical pattern; (6) the outcome was favorable, except in cases
      with bilateral ICVA occlusion.

PMID- 15508939
TI  - Potentiation of haloperidol neurotoxicity in acute hyperthyroidism: report of a
      case.
AB  - Haloperidol has been used extensively for the treatment of many psychiatric
      illnesses as well as for control of agitated patients. Side effects including
      anticholinergic, extrapyramidal, sedative side effects as well as neuroleptic
      malignant syndrome are not unusual. Many factors may contribute to these
      complications including withdrawal or toxicity, concomitant use of other
      medications or the underlying illness itself. We report a case without previous
      history of thyroid disorder sufferring acute manic episode. Haloperidol was
      prescribed to control psychotic symptoms. Symptoms and signs of extrapyramidal
      syndrome, catatonia and hyperthyroidism ensued. Prescription of anti-thyroid
      agents and discontinuation of haloperidol were essential in the successful
      treatment of this patient. It is hypothesized that underlying hyperthyroidism
      might have precipitated haloperidol neurotoxicity. Haloperidol might play a role
      in the exacerbation of hyperthyroidism.

PMID- 15508940
TI  - Concomitant stroke and Candida parapsilosis native valve endocarditis: report of
      one case and literature review.
AB  - Cerebrovascular stroke due to Candida (C.) parapsilosis native valve endocarditis
      (NVE) is rarely reported. Herein, we report a 53-year man with C. parapsilosis
      NVE and acute ischemic stroke. Diabetes mellitus and recent dental manipulation
      were the preceding events. Cranial magnetic resonance imaging study revealed
      occlusion of left common carotid artery, and infarcts of the pons and territory
      of the branch of left middle cerebral artery. With a total of 4,051 mg
      amphotericin B therapy and aortic valve replacement, the patient survived with
      right hemiplegia and dysarthria. In the English literature, there have been 12
      patients with C. parapsilosis NVE including our patient over the past 25 years.
      Intravenous drug abuse was the most common predisposing factor for this infective
      disorder, followed by hematological malignancy and central venous
      catheterization. Fever and ischemic phenomenon of lower legs were the common
      clinical manifestations. Cerebrovascular stroke was present only in our case. Of
      these 12 patients, one administered fluconazole and miconazole therapy died,
      while 11 with amphotericin B therapy and one patient with fluconazole monotherapy
      survived.

PMID- 15508941
TI  - [Another seizure classification--Semiological Seizure Classification].
AB  - The International League Against Epilepsy (ILAE) introduced in 1981 a seizure
      classification based on clinical semiology, interictal EEG findings, and ictal
      EEG patterns. Such classification depends heavily on detailed electroclinical
      correlation. After 20 years' progress in epileptology, many clinicians have found
      it difficult to make a "definite" seizure diagnosis clinically without a series
      of electrophysiological examinations, particularly in the infants, and further
      advancement in epileptology has findings have made the previous classification
      inefficient. Luders and colleagues have proposed a classification, Semiological
      Seizure Classification (SSC), based exclusively on ictal semiology, which was
      published in the official journal of ILAE-EPILEPSIA in 1998. The EEG,
      neuroimaging and other laboratory results should be analyzed separately and then
      integrated to define the epileptic syndromes. The seizure diagnosis is thus made
      through a "what-you-see-is-what-you-get" way. It has also provoked an extensive
      discussion about the necessity of this new classification. In this review, we
      present the original guideline, which has been used at The Cleveland Clinic
      Foundation for years, to introduce another method of epileptic seizure
      classification.

PMID- 15508942
TI  - Cost-effectiveness analysis of tissue plasminogen activator for acute ischemic
      stroke: a comparative review.
AB  - PURPOSE: This work was undertaken to review current evidence of cost
      effectiveness analysis (CEA) on thrombolysis for acute ischemic stroke. METHODS:
      An electronic search via PubMed, from 1995 until May 2004, was performed. The
      methods undertaken by these studies were examined with particular attention to
      their modeling assumptions, sources of data, and outcome measures. RESULTS: Three
      comprehensive CEAs of rtPA (recombinant tissue plasminogen activator) for acute
      ischemic stroke were reviewed. These studies were from the United States, Canada,
      and the United Kingdom. All these studies employed the perspective of a
      healthcare system and used a Markov decision-analytic modelling approach.
      Estimates of effectiveness of rtPA were based on the National Institute of
      Neurological Disorders and Stroke (NINDS) rtPA Stroke Trial, literature-derived
      values or a stroke registry. In each study, functional outcome measured by the
      modified Rankin Scale was used to represent health states, and quality-adjusted
      life year gained was the health outcome summary measure. The cost-effectiveness
      of rtPA therapy varied in magnitude, but seemingly with same positive
      implications. CONCLUSIONS: Cost-effectiveness analysis requires information on an
      intervention's effectiveness and country-specific sources of epidemiological and
      resource utilization data, most of which are not yet available in Taiwan. Despite
      the limitations, CEA is essential if a healthcare system would like to contain
      costs while maintaining, or improving, quality of care.

PMID- 15508943
TI  - Orolingual dyskinesia in central pontine myelinolysis.

PMID- 15508944
TI  - An RN life of learning.

PMID- 15508945
TI  - RN career draws mother and daughter closer.

PMID- 15508946
TI  - RN forges partnerships to help seniors overcome barriers to health and fitness.

PMID- 15508947
TI  - When disaster strikes: treating patients when your department shuts down.

PMID- 15508949
TI  - ED managers should interface with community.

PMID- 15508948
TI  - Space, staff key concerns in ED surge capacity plans.
AB  - As the community's front door, the ED is the first to feel the impact of a sudden
      influx of patients following a disaster. Make sure you have a plan in place to
      use unconventional space, such as the cafeteria, should the need arise. Adjusting
      your triage protocols and canceling elective surgeries can free additional space.
      Know ahead of time which doctors and nurses will be available if the need arises
      for additional staff.

PMID- 15508950
TI  - ED sees 50% reduction in time from triage to ED bed.
AB  - You can see dramatic real-world improvements with benchmarking. Some facilities
      benchmark by modeling a single facility with a successful program. Lehigh Valley
      Hospital in Allentown, PA, reduced its time from triage to ED bed from 37.8
      minutes monthly average to 16.8 minutes monthly average. Saint Rita's Medical
      Center in Lima, OH, slashed overall length of stay from 190 minutes to 150
      minutes.

PMID- 15508951
TI  - Child life services can provide competitive edge.
AB  - Adding child life services to your ED can yield big dividends in patient
      compliance and satisfaction. Distraction techniques often can eliminate the need
      for pharmacological intervention in pain management. The ED manager should
      supervise the specialist, but flexibility should be allowed to enable emotional
      triage. Salary can be justified if 15,000 to 20,000 pediatric patients are seen
      annually.

PMID- 15508952
TI  - Daily satisfaction surveys yield weekly improvements.
AB  - By regularly surveying patients and staff, you can stay on top of key issues that
      need to be addressed. Daily surveys are easily done with a representative
      sampling of patient census and key staff members. Addressing staff complaints in
      a timely manner can contribute to decreased turnover rate. Small changes are
      easier to accomplish than major ones and often can be just as meaningful.

PMID- 15508953
TI  - Bridging the gap in mental health.

PMID- 15508954
TI  - The dangers of diminishing the EN role.

PMID- 15508955
TI  - EN skills must be retained.

PMID- 15508956
TI  - Apology for Nursing Council 'insult'.

PMID- 15508958
TI  - Calling for respect and recognition.

PMID- 15508957
TI  - Objecting to writing a portfolio.

PMID- 15508959
TI  - Obstetric experience will be missed.

PMID- 15508960
TI  - Myths and facts about back injuries.

PMID- 15508962
TI  - New nurses face endemic violence.

PMID- 15508963
TI  - Nursing innovation at the heart of immunisation campaign.

PMID- 15508964
TI  - Measuring on-the-job stress accurately.

PMID- 15508965
TI  - Liaising between the police and mental health. Interview by Teresa O'Connor.

PMID- 15508966
TI  - Caring for prisoners' mental health.

PMID- 15508967
TI  - Northland celebrates 100 years of midwifery.

PMID- 15508968
TI  - A farewell to midwifery.

PMID- 15508969
TI  - Dealing with mental health stigma at work. Interview by Anne Manchester.

PMID- 15508970
TI  - Meeting the needs of refugee children.

PMID- 15508971
TI  - Honouring Putiputi O'Brien at Te Runanga hui. Bay of Plenty/Tairawhiti hosts
      annual general hui.

PMID- 15508972
TI  - Nurses under pressure during restructures and reviews.

PMID- 15508973
TI  - What if we really cared?

PMID- 15508974
TI  - ODA membership advantages.

PMID- 15508975
TI  - Mercury pollution: fact or fiction?

PMID- 15508976
TI  - Profile: Dr. Karen Rattan & Rep. Lance Cargill.

PMID- 15508977
TI  - Medicaid deferral program.

PMID- 15508978
TI  - Oral pathology case--ulcerated palatal swellings.

PMID- 15508979
TI  - A 5,500 year old artificial human tooth from Egypt: a historical note.
AB  - Archaeological excavations at a Neolithic cemetery near Gebel Ramlah, Egypt
      yielded, among other finds, a life-size shell carving of a human tooth. Based on
      its spatulate crown and large conical root, the tooth most closely emulates a
      maxillary incisor. The crown's lingual and labial surfaces are suggestive of a
      left central incisor, whereas the occlusal view is more reminiscent of a left
      lateral incisor. The present report details the tooth's appearance and provides
      several interpretations concerning its function, including the possibility that
      it was intended to be a dental implant.

PMID- 15508980
TI  - Critical bending moment of implant-abutment screw joint interfaces: effect of
      torque levels and implant diameter.
AB  - PURPOSE: Critical bending moment (CBM), the moment at which the external nonaxial
      load applied overcomes screw joint preload and causes loss of contact between the
      mating surfaces of the implant screw joint components, was measured with 2 types
      of implants and 2 types of abutments. MATERIALS AND METHODS: Using 4 test groups
      of 5 implant-abutment pairs, CBM at the implant-abutment screw joint was measured
      at 25%, 50%, 75%, and 100% of the manufacturer's recommended torque levels.
      Regular Platform (RP) Nobel Biocare implants (3.75 mm diameter), Wide Platform
      (WP) Nobel Biocare implants (5.0 mm diameter), CeraOne abutments, and Multiunit
      abutments were used. Microstrain was measured as loads were applied to the
      abutment at various distances from the implant-abutment interface. Strain
      instrumentation logged the strain data dynamically to determine the point of gap
      opening. All torque applications and strain measurements were repeated 5 times.
      RESULTS: For the CeraOne-RP group, the mean CBMs were 17.09 Ncm, 35.35 Ncm, 45.63
      Ncm, and 62.64 Ncm at 25%, 50%, 75%, and 100% of the recommended torque level,
      respectively. For the CeraOne-WP group, mean CBMs were 28.29 Ncm, 62.97 Ncm,
      92.20 Ncm, and 127.41 Ncm; for the Multiunit-RP group, 16.08 Ncm, 21.55 Ncm,
      34.12 Ncm, and 39.46 Ncm; and for the Multiunit-WP group, 15.90 Ncm, 32.86 Ncm,
      43.29 Ncm, and 61.55 Ncm at the 4 different torque levels. Two-way analysis of
      variance (ANOVA) (P < .001) revealed significant effects for the test groups (F =
      2738.2) and torque levels (F = 2969.0). DISCUSSION: The methodology developed in
      this study allows confirmation of the gap opening of the screw joint for the test
      groups and determination of CBM at different torque levels. CONCLUSION: CBM was
      found to differ among abutment systems, implant diameters, and torque levels. The
      torque levels recommended by the manufacturer should followed to ensure screw
      joint integrity.

PMID- 15508981
TI  - Improved retention and bone-tolmplant contact with fluoride-modified titanium
      implants.
AB  - PURPOSE: The purpose of the present study was to investigate whether a fluoride
      modification of the titanium surface would have an effect on bone response after
      implantation. MATERIALS AND METHODS: Titanium-oxide-blasted titanium implants
      with and without fluoride modification were investigated in a rabbit tibia model.
      Quantitative analysis of surface roughness, biomechanical interlocking, and in
      vivo tissue reactions in rabbit bone at 1 and 3 months after placement were
      compared. RESULTS: The fluoride-modified test implants had a slightly smoother
      surface (Sa: 0.91 +/- 0.14 microm) than the unmodified control implants (Sa: 1.12
      +/- 0.24 microm). Significantly higher removal torque values (85 +/- 16 Ncm vs 54
      +/- 12 Ncm) and shear strength between bone and implants (23 +/- 9 N/mm2 vs 15 +/
      5 N/mm2) were measured for the fluoride-modified implants after 3 months. The
      histomorphometric evaluations demonstrated higher bone-to-implant contact for
      test implants at 1 month (35% +/- 14% vs 26% +/- 8%) and 3 months (39% +/- 11% vs
      31% +/- 6%) after placement. DISCUSSION: Implant surface modification with
      fluoride may result in morphologic and physiochemical phenomena that are of
      significance for the bone response. Another possible explanation for the findings
      in the present study is that a surface modification changes the surface chemical
      structures to be more suitable for bone bonding. CONCLUSION: Based on the
      biomechanical and histomorphometric data, the fluoride-modified titanium implants
      demonstrated a firmer bone anchorage than the unmodified titanium implants. These
      implants achieved greater bone integration than unmodified titanium implants
      after a shorter healing time.

PMID- 15508982
TI  - Osseointegration of dental implants complexed with rhBMP-2: a comparative
      histomorphometric and radiographic evaluation.
AB  - PURPOSE: To evaluate the effect of rhBMP-2 on implant osseointegration using
      histomorphometric and radiographic imaging analyses and determine the diagnostic
      accuracy of periapical radiographs regarding clinical bone-implant contact
      levels. MATERIALS AND METHODS: Hollow-cylinder implants were filled with an
      absorbable collagen sponge soaked with recombinant human bone morphogenetic
      protein-2 (rhBMP-2) or left empty and implanted in the mandibles of dogs. Animals
      were followed for 2, 4, 8, or 12 weeks. At the end of each time interval, the
      animals were sacrificed and specimens were collected for histomorphometric and
      radiographic evaluation of the bone-implant contact levels. RESULTS: Both groups
      exhibited the same mean histologic bone-implant contact on the outer surface of
      the implant, except for the 4-week group. The radiographic evaluation of bone
      implant contact overestimated the actual osseointegration levels by at least 30%,
      a significant amount. DISCUSSION: The osteoinductive and regenerative potential
      of rhBMP-2 is of clinical benefit in cases where bone augmentation is indicated
      and improved levels of osseointegration are expected. Radiographic evaluation has
      been the most widely employed technique in clinical practice for assessing bone
      levels around dental implants and comparing changes over time. However, there is
      a limit to the diagnostic accuracy of conventional radiographs when compared to
      the data obtained by histologic analysis. CONCLUSION: Application of rhBMP-2
      within the confined boundaries of the hollow chamber of the implant had a limited
      effect on the osseointegration level along its outer surface, perhaps because of
      physically restricted diffusion. Radiographic evaluation resulted in the
      overestimation of bone-implant contact, and poor correlation with the
      histomorphometric data was found.

PMID- 15508983
TI  - Histomorphometric analysis of homogenous demineralized dentin matrix as
      osteopromotive material in rabbit mandibles.
AB  - PURPOSE: The aim of this work was to evaluate the effectiveness of homogenous
      demineralized dentin matrix (HDDM) slices in surgical bone defects created in the
      mandibles of rabbits and occluded with a polytetrafluoroethylene (PTFE) membrane
      in the promotion of bone growth. MATERIALS AND METHODS: Surgical bone defects
      were created in 36 adult rabbits and divided into 4 groups: bone defect
      (control), bone defect with PTFE membrane, bone defect with HDDM, and bone defect
      with both HDDM and a PTFE membrane (HDDM + PTFE). The rabbits were sacrificed
      after 30, 60, and 90 days, and the bone defects were examined histologically and
      by histomorphometric analysis (analysis of variance and the Tukey test). RESULTS:
      The volume of newly formed bone matrix was significantly greater in the HDDM and
      HDDM + PTFE groups than in the control and PTFE groups. The discrete inflammatory
      reaction found in the HDDM and HDDM + PTFE groups did not prevent the
      osteopromotive activity of the dentin matrix. DISCUSSION: HDDM slices were
      biocompatible and were resorbed during the bone remodeling process. They
      stimulated the newly formed bone until 30 days after implantation. CONCLUSION:
      Bone repair was accelerated in the bone defects treated with HDDM in comparison
      to the control group.

PMID- 15508984
TI  - Osteoporosis-like bone conditions affect osseointegration of implants.
AB  - PURPOSE: Usage of dental implants has become common for the treatment of
      edentulous patients, but concerns exist over the use of implants in patients
      where orofacial bone loss occurs. In the present study, the osseointegration of
      implants in rabbits under osteoporosis-like (OP-like) conditions simulating
      several clinically relevant conditions is reported. MATERIALS AND METHODS: Forty
      rabbits were divided into 4 groups of 10. Three groups of animals received daily
      intramuscular injections of glucocorticoids (7.5 mg/kg) for 8 weeks to induce OP
      like conditions either before, simultaneous to, or after implant placement.
      RESULTS: The injections of glucocorticoids resulted in cortical thinning,
      irregular trabecular patterns, and impaired extracellular (ECM) matrix formation
      and mineralization. Although interfacial strength (8.5 +/- 1.3 MPa for the
      control group; 9.3 +/- 4.0 to 10.1 +/- 4.0 MPa for the experimental groups) was
      apparently not affected in this limited sample cohort (n = 3 per group),
      statistically significant decreases (P < .05) in implant-bone contact were
      observed in animals with OP-like conditions (49% +/- 10% for the control group;
      24% +/- 16% to 42% +/- 16% for the experimental groups). DISCUSSION: Histologic
      features characteristic of OP-like conditions were observed in each experimental
      group. ECM expression also appeared to be altered and compromised in all animals
      with OP-like conditions, which may affect long-term biomechanical stability of
      the implants. CONCLUSION: OP-like conditions affect the osseointegration
      characteristics of implants, but long-term biomechanical stability under forces
      of mastication is unknown as yet.

PMID- 15508985
TI  - A 10-year randomized clinical trial on the influence of splinted and unsplinted
      oral implants retaining mandibular overdentures: peri-implant outcome.
AB  - PURPOSE: This randomized controlled clinical trial aimed to evaluate the efficacy
      of splinted implants versus unsplinted implants in overdenture therapy over a 10
      year period. MATERIALS AND METHODS: The study sample comprised 36 completely
      edentulous patients, 17 men and 19 women (mean age 63.7 years). In each patient,
      2 implants (Branemark System, Nobel Biocare, Goteborg, Sweden) were placed in the
      interforaminal area. Three to 5 months after placement, they were connected to
      standard abutments. The patients were then rehabilitated with ball-retained
      overdentures, magnet-retained overdentures, or bar-retained overdentures (the
      control group). Patients were followed for 4, 12, 60, and 120 months post
      abutment connection. Group means as well as linear regression models were fitted
      with attachment type and time as classification variables and corrected for
      simultaneous testing (Tukey). RESULTS: After 10 years, 9 patients had died and 1
      was severely ill. Over 10 years, no implants failed. Mean Plaque Index, Bleeding
      Index, change in attachment level, Periotest values, and marginal bone level at
      the end of the follow-up period were not significantly different among the
      groups. DISCUSSION: The annual marginal bone loss, excluding the first months of
      remodeling, was comparable with that found around healthy natural teeth.
      CONCLUSION: The fact that no implants failed and that overall marginal bone loss
      after the first year of bone remodeling was limited suggested that implants in a
      2-implant mandibular overdenture concept have an excellent prognosis in this
      patient population, irrespective of the attachment system used.

PMID- 15508986
TI  - Clinical evaluation of small-diameter implants in single-tooth and multiple
      implant restorations: a 7-year retrospective study.
AB  - PURPOSE: Placement of small-diameter implants often provides a solution to space
      related problems in implant restoration. This 7-year retrospective study presents
      results from 192 small-diameter implants placed in 165 patients from 1992 to
      1996. MATERIALS AND METHODS: The dental records of each patient were reviewed.
      The implants, which were either 2.9 mm or 3.25 mm in diameter, were placed by 2
      different surgeons. All prosthetic appliances were fabricated by the same
      prosthodontist. Ninety-four implants supported single-tooth cemented
      restorations; the remaining 98 implants supported cemented or screw-retained
      partial prostheses. RESULTS: The total implant survival rate was 95.3%. Four
      implants were lost at second-stage surgery, and 5 more were lost after loading.
      DISCUSSION: Small-diameter implants demonstrated a survival rate similar to those
      reported in previous studies of standard-size implants. CONCLUSIONS: The results
      suggest that small-diameter implants can be successfully included in implant
      treatment. They may be preferable in cases where space is limited.

PMID- 15508987
TI  - Clinical analysis of wide-diameter frialit-2 implants.
AB  - PURPOSE: To evaluate wide-diameter (ie, 5.5-mm-wide) Frialit-2 implants used for
      several forms of prosthetic rehabilitation. MATERIALS AND METHODS: In this
      retrospective study, 121 wide implants (74 maxillary, 47 mandibular) were placed
      in 114 patients (61 female, 53 male, mean age 37.2 +/- 14.9 years). Thirty-six
      single-tooth restorations, 63 fixed partial dentures (68 implants), 6 removable
      overdentures (7 implants), and 3 fixed complete dentures (8 implants) were
      placed. Eighty-seven were placed in the molar regions. The follow-up period for
      the implants was 12 to 114 months (mean 41.8 +/- 18.5 months). Peri-implant bone
      loss, pocket depth, Plaque Index values, Bleeding Index values, and Periotest
      values were evaluated. RESULTS: Overall, 2 maxillary implants were lost, for a
      cumulative survival rate of 98.3% (97.3% in the maxilla; 100% in the mandible).
      Mean peri-implant pocket depth (3.4 +/- 1.1 mm), bone resorption (1.4 +/- 1.2
      mm), Periotest values (-4.3 +/- 3.1) as well as the Plaque Index and Bleeding
      Index (grades of 0 in 80% of cases) indicated acceptable results. DISCUSSION: The
      high survival rate may be attributed to avoidance of the use of short wide
      diameter implants, and the primary intention to place wide-diameter implants.
      Preference of the molar region was a consequence of the peri-implant bone
      situation in the premolar region, which was frequently inadequate for a 5.5-mm
      implant. CONCLUSIONS: The use of wide-diameter implants can be a viable treatment
      option and may provide benefits in posterior regions for long-term maintenance of
      various implant-supported prosthetic rehabilitations. Some anatomic and
      prosthodontic limitations for the use of wide implants were

PMID- 15508988
TI  - Clinical trial of modified ankylos implants for extraoral use in cranio- and
      maxillofacial surgery.
AB  - PURPOSE: Epithetic solutions in the maxillofacial region are indicated if plastic
      surgery reconstruction is not a valid option for an extensive defect. The purpose
      of this study was to examine whether the extraoral implants used provided
      sufficient retention to be used as anchoring aids. MATERIALS AND METHODS: Between
      November 1999 and September 2002, 33 identical modified Ankylos implants for
      extraoral anchorage were placed in 10 patients for the fixation of various
      epitheses in the midfacial (eye, nose) and ear regions in the course of a
      clinical trial. RESULTS: Over a follow-up period of 2 to 34 months, all implants
      remained osseointegrated (as confirmed radiographically), and the implants and
      epithetic restorations were clinically stable. DISCUSSION: The results
      demonstrated that the lasting retention of maxillofacial epitheses provided by
      implants assures patients that their epitheses are securely fixed. CONCLUSION:
      The demonstrated extraoral implant system not only achieved sufficient
      osseointegration but also showed good clinical handling and easy fixation
      possibilities for epithetic anchorage.

PMID- 15508989
TI  - Immediate loading of dental implants in the completely edentulous maxilla: a
      clinical report.
AB  - PURPOSE: The purpose of this article was to determine whether clinical success
      can be achieved with immediate loading in the completely edentulous maxilla with
      endosseous screw-type implants. MATERIALS AND METHODS: The study sample consisted
      of 34 patients who were edentulous or about to lose all remaining maxillary
      teeth. The patients underwent an extensive presurgical and prosthetic workup to
      determine whether they qualified for the study. Sufficient osseous structure to
      place 6 to 8 implants with a minimum length of 8 mm was required. Provisional
      prostheses were fabricated either chairside on the day of implant placement or in
      a laboratory from an impression. The abutments and temporary restorations were
      placed 48 to 72 hours postsurgery. RESULTS: A total of 236 implants were placed
      in 34 patients. Sixteen implants were lost in 11 patients; thus the survival rate
      was 93%. All patients subsequently received definitive maxillary restorations.
      DISCUSSION: The major cause of implant failure appeared to be micromotion during
      healing. This was the result of either a non-passively fitting restoration or
      noncompliance (eg, eating chewing hard foods before the implants had integrated).
      CONCLUSIONS: This clinical report suggests that immediate loading of implant
      supported restorations in the completely edentulous maxilla was a viable
      treatment alternative for this patient population.

PMID- 15508990
TI  - Injury to the inferior alveolar nerve during implant placement: a formula for
      protection of the patient and clinician.
AB  - This article concerns the problem of nerve damage associated with implant
      placement in the posterior mandible. The causes are discussed, with particular
      emphasis on intrusion of the drill or implant into the nerve canal.
      Recommendations are made to help the practitioner avoid this too-common
      complication.

PMID- 15508992
TI  - Accuracy of a manual torque application device for morse-taper implants: a
      technical note.
AB  - PURPOSE: The objective of this study was to compare torques applied by new and
      used manual torque devices for Morse-taper implants. MATERIAL AND METHODS:
      Fifteen ITI manual torque devices were tested. Those in group 1 (n = 5) were new
      (ie, never used), those in group 2 (n = 5) had been used 50 to 200 times, and
      those in group 3 (n = 5) had been used 500 to 1,000 times. The torques applied by
      each device were measured for 35 Ncm and 15 Ncm targets in an experimental setup
      by a custom-made wrench with strain gauges connected to a data acquisition
      system. The strain-gauge signals were simultaneously delivered to a computer at a
      sample rate of 10,000 Hz and converted to torque units. RESULTS: New devices
      applied higher torques than used devices for the 35-Ncm torque target (P < .05).
      The torques applied by group 3 devices were approximately 1.5 Ncm lower than
      those of other groups for the 35-Ncm target and approximately 1 Ncm lower for the
      15-Ncm target. DISCUSSION AND CONCLUSION: ITI manual torque devices deliver
      consistent torque output, although a slight decrease occurs as a consequence of
      clinical use.

PMID- 15508991
TI  - Influence of superstructure materials on strain around an implant under 2 loading
      conditions: a technical investigation.
AB  - PURPOSE: This investigation was concerned with the effect of 3 superstructure
      materials on the strain around an implant under static and nonimpact dynamic
      loading. MATERIALS AND METHODS: Five highly filled composite resin-veneered crown
      analogs, 5 autopolymerized acrylic resin-veneered crown analogs, and 5 gold-alloy
      full cast crown analogs were prepared. The resin veneers were applied to gold
      alloy frameworks. These crown analogs were prepared to fit an ITI implant
      abutment assembly, which was screwed into a block of acrylic resin to simulate
      implantation in bone. The crown analogs were successively placed on the abutment,
      and a lateral load of 100 N was applied to the superstructure by a lever-type
      testing machine. Strains were recorded under static and dynamic loading by a 2mm
      long strain gauge bonded to the surface of the bone simulant tangential to the
      implant. The dynamic load simulated masticatory cycles (75 strokes/min). RESULTS:
      Although the strain values differed significantly between the static and dynamic
      loading (P < .05), there was no significant difference among the superstructure
      materials under either loading condition (P > .05). DISCUSSION: These findings
      are in agreement with in vivo measurements, thus suggesting that cyclic rather
      than impact loading should be used in the investigation of occlusal material
      behavior under functional loading. CONCLUSION: Under static and nonimpact dynamic
      loading, the 3 superstructure materials tested (highly filled composite resin,
      acrylic resin, and gold alloy) had the same influence on the strain transmitted
      to a bone simulant that surrounded a single implant.

PMID- 15508993
TI  - Dental rehabilitation using an implant-supported overdenture after repair of a
      fracture in a severely resorbed edentulous mandible: a case report.
AB  - Treatment of mandibular fracture in senior citizens with severely resorbed
      edentulous mandibles is extremely difficult. Such treatment must achieve
      successful osteosynthesis and restore functional mastication. A severely resorbed
      (Class V) mandible was successfully reconstructed with an autogenous bone graft
      on the inferior border of the mandible and a titanium mesh plate after a failed
      attempt to fix the fracture. After the placement of endosseous implants in the
      mandible, the patient was rehabilitated with an overdenture to restore
      masticatory function.

PMID- 15508994
TI  - Distraction osteogenesis in an anterior mandibular bone defect utilizing lingual
      periosteal release: a case report.
AB  - This clinical report presents a modified distraction technique to achieve height
      in the vector of distraction. The success of distraction osteogenesis depends on
      both biologic and biomechanical factors. The focus in this case is on correcting
      the direction of distraction; incorrect distraction direction is a frequent
      complication associated with distraction osteogenesis in the mandible. A 21-year
      old man presented with a 10-mm vertical bone defect in the anterior mandible
      caused by facial trauma. The treatment chosen was distraction osteogenesis. After
      osteotomizing a bone segment and slitting the lingual periosteum, the bone
      segment was advanced anteriorly 4 mm and an extra-alveolar distraction device was
      applied. This approach allows the distraction device to be placed vertically,
      thus preventing lingual shift. The newly created alveolar ridge fully met
      prosthodontic requirements for a predictable outcome.

PMID- 15508995
TI  - Maintaining vector control during alveolar distraction osteogenesis: a technical
      note.
AB  - Distraction osteogenesis is a predictable method for restoring missing tissue
      prior to implant placement. However, pull from the soft tissue can alter the
      desired direction of the distraction. This article describes and illustrates
      techniques that are useful for maintaining the desired vector during alveolar
      distraction osteogenesis. These methods can prevent the need for further
      intervention and allow for ideal placement of endosseous dental implants without
      compromising results.

PMID- 15508996
TI  - RDC/TMD criteria.

PMID- 15508997
TI  - Topical review: new insights into the pathology and diagnosis of disorders of the
      temporomandibular joint.
AB  - The collection of conditions affecting the temporomandibular joint (TMJ) and
      masticatory muscles, the so-called temporomandibular disorders, can be classified
      according to the Research Diagnostic Criteria for Temporomandibular Disorders. Of
      the 3 subgroups--muscle disorders (Group I); disc displacements (Group II); and
      arthralgia, arthritis, and arthrosis (Group III)--the muscle disorders are most
      frequently seen in community samples; Group II and Group III diagnoses are less
      prevalent. This may explain the relative scarcity of studies involving
      intracapsular TMJ disorders. In this review, new insights into the functional
      anatomy, imaging, and pathology of disorders of the TMJ are presented. Studies of
      TMJ dynamics may provide insight into the functional anatomy of the TMJ and
      thereby into the consequences of Group II and Group III disorders. The clinical
      use of imaging modalities such as computed tomography and magnetic resonance
      imaging for the TMJ and related structures remains controversial. Nevertheless,
      imaging is regularly used in the diagnosis of some Group II and Group III
      disorders. Magnetic resonance imaging may be of use not only for the
      visualization of disc displacements but also for the study of bone mineral
      density of the condyle. Cytokines such as interleukin-1 (IL-1) and tumor necrosis
      factor alpha (TNFalpha) play an important role in TMJ pathology. For example, IL
      1beta, which has been associated with TMJ pain, hyperalgesia, and anterior bite
      opening, is mostly absent in the synovial fluid of healthy joints. Since both IL
      1 and TNFalpha are involved in the development of chronic pain and joint
      destruction, they may be the targets for specific treatments. While the advances
      reviewed in this paper are significant, multidisciplinary efforts and formation
      of international research collaborations will be necessary to continue
      advancement in the understanding of TMJ pathology and diagnosis.

PMID- 15508998
TI  - Improved interaction models of temporomandibular joint anatomic relationships in
      asymptomatic subjects and patients with disc displacement with or without
      reduction.
AB  - AIMS: To consider temporomandibular joint (TMJ) anatomic interactions in order to
      refine hard tissue models differentiating (1) joints diagnosed with disc
      displacement with reduction (DDwR) or without reduction (DDw/oR) from
      asymptomatic joints (Normals), and (2) DDwR joints from DDw/oR joints. METHODS:
      TMJ tomograms of 84 women with unilateral DDwR and 78 with unilateral DDw/oR were
      compared against each other and against those of 42 female Normal joints through
      the use of 14 linear and angular measurements, 8 ratios, and 34 interactions. A
      classification tree model for each comparison was tested for fit with
      sensitivity, specificity, accuracy, and log likelihood and compared to logistic
      regression models. RESULTS: In the classification tree model comparison, the DDwR
      model versus the Normal model realized 35.9% log likelihood (88.0% sensitivity,
      66.7% specificity); the DDw/oR model versus the Normal model realized 38.8% log
      likelihood (69.6% sensitivity, 85.7% specificity). The DDwR model versus the
      DDw/oR model realized 33.3% log likelihood (76.0% sensitivity, 73.1%
      specificity). In the logistic regression model comparison, the DDwR model versus
      the Normal model realized 40.8% log likelihood (82.1% sensitivity, 78.6%
      specificity) and the DDw/oR model versus the Normal model realized 61.1% log
      likelihood (85.9% sensitivity, 90.5% specificity). The DDwR model versus the
      DDw/oR model realized 21.5% log likelihood (60.3% sensitivity, 79.8%
      specificity). The addition of interactions to the logistic regression models
      improved the previously published log likelihood from 99% to 149%. CONCLUSION:
      The interactions improved logistic regression models and the data suggest that
      anatomic characteristics influence joint functional status. Because the models
      incorporated nearly all considered anatomic measurements, no anatomic factor is
      redundant in the closed TMJ biological system.

PMID- 15508999
TI  - Short-term clinical outcomes and patient compliance with temporomandibular
      disorder treatment recommendations.
AB  - AIMS: To evaluate short-term patient compliance with 5 conservative
      temporomandibular disorder (TMD) treatments (jaw relaxation, jaw stretching, heat
      application, cold application, and occlusal splint use) and the association of
      compliance with changes in pain intensity, pain-related activity interference,
      and jaw use limitations. METHODS: Eighty-one TMD patients were given 1 to 5
      treatment recommendations as part of usual care in a TMD specialty clinic.
      Compliance with each recommendation and pain, pain-related activity interference,
      and jaw use limitation measures were calculated from electronic interviews
      conducted 3 times daily for 2 weeks. RESULTS: Median compliance with individual
      treatment modalities ranged from 7.7% for heat application to 92.7% for jaw
      relaxation; median overall compliance was 54.8%. Participants with higher initial
      pain intensity and jaw use limitations were significantly more compliant with
      their recommended treatment regimen (P < .05). The authors controlled for age,
      gender, education, and initial jaw use limitations. Overall compliance was
      associated significantly and positively with 2-week jaw use limitations (P =
      .03). A trend toward a statistically significant positive association was found
      between compliance and 2-week pain intensity (P = .09). CONCLUSION: Compliance
      varied widely across patients and therapies. Patients with higher initial pain
      and jaw use limitation levels were more compliant with treatment recommendations.
      Although compliance was associated with slight increases in pain and jaw use
      limitations in this preliminary study, further research is needed to evaluate the
      longer-term effects of compliance with recommended therapies.

PMID- 15509000
TI  - Comparison of algometry and palpation in the recognition of temporomandibular
      disorder pain complaints.
AB  - AIMS: To determine the construct validity of algometry and to compare it with
      that of palpation, and to compare tenderness of masticatory muscle sites and the
      temporomandibular joint (TMJ) on palpation and on algometry. METHODS: Two hundred
      fifty subjects, 148 with temporomandibular disorder (TMD) pain complaints,
      underwent a standardized blinded physical examination that included pain
      intensity measures on palpation and pressure pain threshold measures on algometry
      of masseter muscle sites, temporalis muscle sites, and the TMJ. RESULTS: Logistic
      regression analysis indicated that the recognition of TMD pain complaints based
      on pressure algometry was comparable to that of palpation (R2 = 0.22 and R2 =
      0.21, respectively). The masseter muscles were most tender to palpation and
      algometry, followed by the TMJs and the temporalis muscles. CONCLUSION: Construct
      validity of algometry in the recognition of TMD pain complaints is comparable to
      that of palpation, and differences in tenderness on palpation and on algometry
      are found between masticatory muscle sites and the TMJ.

PMID- 15509001
TI  - Relationships between depression/somatization and self-reports of pain and
      disability.
AB  - AIMS: To examine the relationship between depression and somatization and pain
      during muscle and joint palpation as well as limitations related to mandibular
      functioning (LRMF) in patients with temporomandibular disorders. METHODS: The
      Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) data for
      Axes I and II for 196 consecutive patients (56 men and 140 women) with a history
      of facial pain were obtained. The mean age of the predominantly Chinese patient
      population (83.2%) was 33.4 years (range 18 to 55 years). A computerized
      diagnostic system was used to collect the RDC/TMD history data. The Symptom Check
      List (SCL-90) depression and somatization scales were generated on-line and
      archived. The mean muscle pain (MP), joint pain (JP), and LRMF scores were
      computed with depression and somatization as main effects. Data were subjected to
      analysis of variance (Scheffe test) and Pearson's correlation at a significance
      level of .05. RESULTS: Depression scores ranged from 4.03 to 8.16 (MP), from 0.67
      to 1.03 (JP), and from 0.30 to 0.38 (LRMF); somatization scores ranged from 2.64
      to 7.75 (MP), from 0.58 to 1.00 (JP), and from 0.30 to 0.41 (LRMF). Interaction
      effects between depression and somatization were not significant. Patients with
      severe depression had significantly higher MP scores than normal patients or
      patients with moderate depression. Patients with moderate and severe somatization
      had significantly higher MP scores than normal patients. LRMF scores of patients
      with severe somatization were significantly greater than those who were normal or
      suffered from moderate somatization. No significant difference in JP scores was
      observed for depression and somatization scales. Correlations between
      depression/somatization and MP, JP, and LRMF scores were significant and positive
      but weak; coefficients ranged from 0.15 to 0.41. CONCLUSION: The results suggest
      that depression and somatization are related to the self-report of MP. In
      addition, severe somatization may be associated with an increase in jaw
      disability.

PMID- 15509002
TI  - Characteristics of subjects with secondary otalgia.
AB  - AIMS: To investigate whether secondary otalgia is associated with cervical spine
      disorder (CSD), temporomandibular disorders (TMD), or both, and to describe the
      pain characteristics and the comorbidity of secondary otalgia in subjects with
      and without CSD and TMD. METHODS: A mailed questionnaire was sent to a random
      sample of 2,500 people aged 25 to 65 years. Altogether 1,720 recipients
      responded. Inclusion criteria were pain inside or around the ear without
      infection, tumor, or trauma, of 6 or more months duration, and a pain frequency
      of at least once a month. Altogether 152 respondents fulfilled the criteria, and
      of these 100 participated in the clinical examinations and interviews. RESULTS:
      Based on standardized examinations and interviews, 91 subjects had secondary
      otalgia and 9 had primary otalgia. Most (85%) of the 91 subjects with secondary
      otalgia also had signs and symptoms of TMD and/or CSD and were therefore
      classified into 3 groups: CSD (35%), TMD (20%), or "Combination," ie, signs and
      symptoms of both TMD and CSD (30%). Subjects without CSD or TMD (15%) reported
      the same level of intensity and impact of otalgia on daily living and
      psychological distress as the others but less frequent head and neck pain and
      fewer sleep-related problems. CONCLUSIONS: Most of the subjects reporting
      secondary otalgia also suffered from CSD or TMD or both. Thus, in patients with
      secondary otalgia, an examination of the cervical spine and the stomatognathic
      system should be routinely performed.

PMID- 15509003
TI  - Individual variations in numerically modeled human muscle and temporomandibular
      joint forces during static biting.
AB  - AIMS: To test the effects of occlusal force (OF) angle on the variations in
      predicted muscle and temporomandibular joint (TMJ) forces during unilateral molar
      bites. METHODS: The craniomandibular (CM) geometries of 21 individuals were
      determined from lateral and posteroanterior cephalometric radiographs. These
      geometries were used in a numerical model based on minimization of muscle effort.
      This model was previously validated for this subject group through the use of jaw
      tracking and electromyographic data. The model predicted muscle and TMJ forces
      associated with static OFs on the right mandibular first molar. OF angle was
      varied from vertical to 40 degrees in the buccal and lingual directions, in
      increments of 10 degrees. RESULTS: Intra- and intersubject variations in
      predicted muscle and TMJ forces for unilateral molar biting were dependent on OF
      angle and CM geometry. Nonvertical OFs were associated with either large anterior
      temporalis muscle forces (> 100% of applied OF in 3 subjects) or large inferior
      lateral pterygoid muscle forces (> 90% of applied OF in 3 subjects). On average,
      vertically and buccally directed OFs were associated with higher mean
      contralateral TMJ forces (60% of applied OF, SD 12%). Two subjects had large
      ipsilateral or contralateral TMJ forces (> 90% of applied OF). CONCLUSION: In a
      group of healthy subjects, depending on the individual CM geometry, large muscle
      and/or TMJ forces were predicted to be associated with specific unilateral molar
      OF angles. Propensities to increased muscle or joint forces may be predisposing
      factors in the development of myofascial pain or intracapsular disease. The
      results may explain, in part, the variation in location of symptoms in
      individuals who first present with temporomandibular disorders.

PMID- 15509005
TI  - The importance of early recognition of condylar fractures in children: a study of
      2 cases.
AB  - Maxillofacial fractures in general and mandibular fractures in particular seem to
      be less common in children than in adults; however, this finding might be
      influenced by the fact that condylar fractures in children are often undiagnosed
      and so the true incidence is likely to be higher than that reported in
      literature. Traumatic lesions of the temporomandibular joint often are overlooked
      as they can apparently occur with relatively little pain, few clinical signs, and
      insufficient reaction by the child to alert an adult to the seriousness of the
      injury. Only 1 to 2 years later, when growth disturbances appear, are they
      perceived as a problem, but by that time, the dysplastic growth pattern has
      stabilized and will continue over a period of years. The problem is frequently
      underestimated because of the difficulties inherent in pediatric pain assessment.
      The fact that the mechanisms of pain perception in children differ somewhat from
      adult pain perception mechanisms is one factor that can make pediatric pain
      assessment difficult. This paper outlines 2 case reports that draw attention to
      pain in children in the case of temporomandibular joint injury. The inability to
      assess pain adequately may lead to a delay in diagnosis and treatment and
      possibly result in future growth disturbances and facial asymmetries.

PMID- 15509004
TI  - Muscle and brain changes of calcitonin gene-related peptide in experimentally
      induced unilateral rat masseter myositis.
AB  - AIMS: To investigate changes in calcitonin gene-related peptide (CGRP)-like
      immunoreactivity (CGRP-LI) in the rat masseter muscle and brain after the
      unilateral experimental induction of masseter myositis. METHODS: Ipsilateral and
      contralateral changes of the CGRP were examined in rat masseter muscle after the
      induction of unilateral myositis on the right side with an intramuscular
      injection of 0.01 mL Freund's adjuvant. The left masseter, and left and right
      masseters of control rats, were injected with 0.01 mL saline (0.9%). After 21
      days, tissue samples from the masseter muscles and the hypothalamic-pituitary
      adrenal (HPA) axis were analyzed for the presence of CGRP by
      immunohistochemistry, radioactive immunoassay, and high performance liquid
      chromatography. Hematoxylin-eosin staining was used to confirm inflammation in
      the masseter muscles. RESULTS: Elevated CGRP-LI was detected bilaterally in the
      masseter muscles (P < .001) in the myositis group. CGRP-immunoreactive nerve
      fibers were mainly detected in close proximity to muscle cells and in the walls
      of the blood vessels. Compared to the control rats, a significant difference in
      scratching behavior was seen in the myositis group from day 9 until day 21. In
      the myositis group, CGRP-LI was increased in the pituitary gland concomitant with
      the increase in CGRP-LI in the masseter muscles but was decreased in the
      hypothalamus. A possible explanation for these changes could be that rats with
      chronic myositis develop an abnormal function of the HPA axis triggered by
      masseter muscle inflammation. CONCLUSION: The results of this study demonstrate
      that CGRP may play an important role both peripherally and centrally in masseter
      muscle myositis in association with presumed nociceptive behavior.

PMID- 15509006
TI  - U.S. loses half its vaccine doses for coming flu season.

PMID- 15509007
TI  - Perspectives. Next steps tough to discern for covering poor, uninsured.

PMID- 15509008
TI  - Environmental nanomaterials: occurrence, syntheses, characterization, health
      effect, and potential applications.

PMID- 15509009
TI  - Nanostructured materials for environmental remediation of organic contaminants in
      water.
AB  - Nanostructured materials have opened new avenues in various scientific fields and
      are providing novel opportunities in environmental science. The increased surface
      area-to-volume ratio of nanoparticles, quantum size effects, and the ability to
      tune surface properties through molecular modification make nanostructures ideal
      for many environmental remediation applications. We describe herein the
      fabrication of metal and semiconductor nanoparticles for environmental
      remediation applications, particularly in ground water. We then summarize
      literature reports of nanostructures specifically tailored for remediation of
      environmental contaminants including organohalides, trinitrotoluene, and phenols.

PMID- 15509010
TI  - Discoloration and mineralization of non-biodegradable azo dye Orange II by copper
      doped TiO2 nanocatalysts.
AB  - Copper-doped TiO2 nanocatalysts were synthesized by photo-deposition and sol-gel
      methods. The nanocatalysts were characterized by X-ray diffraction (XRD), X-ray
      photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), and the
      BET method. The catalysts' activities in the discoloration and mineralization of
      0.2 mM Orange II were evaluated. The results indicated that the Cu-doped TiO2
      nanocatalysts with a low copper concentration prepared by the photo-deposition
      method showed enhanced photocatalytic activity; while catalysts synthesized by
      the sol-gel method did not. In particular, the TiO2 nanocatalyst doped with 1% Cu
      showed the best performance. Complete color removal and 99% of total organic
      carbon (TOC) removal were achieved after 150-min of reaction. TiO2 nanocatalysts
      doped with more than 1% Cu by the photo-deposition method showed decreased
      photocatalytic activities.

PMID- 15509011
TI  - Toxicity recognition of hepatotoxin, homologues of microcystin with artificial
      trapping devices.
AB  - A hepatotoxin produced by cyanobacteria, microcystin (MC), was
      chromatographically discriminated with newly prepared artificial trapping
      devices. MC involves up to 70 kinds of homologues, and because homologues have
      similar toxicity, effective removal and analysis methods have been required. As a
      trapping device to discriminate MC, we have developed a novel technique for
      preparation of the "imprinted recognition site" into the crosslinked nano-scale
      structure, namely "Fragment Imprinting Effect." This technique is simple, and its
      possible application fields are relatively broad. We have demonstrated the
      recognition for MC homologues through the combination of two different artificial
      molecular recognition devices prepared through fragment imprinting technique.

PMID- 15509012
TI  - Adsorption of some aromatic compounds by a synthetic mesoporous silicate.
AB  - Water pollution by toxic organic compounds is of concern and demands for
      effective adsorbents for removal of the toxic compounds are increasing. Here we
      synthesized a mesoporous material, FSM-16, and investigated its ability to take
      up model compounds (benzene, toluene, phenol, and benzoic acid) from aqueous
      solutions by batch experiments. The adsorption isotherms were linear and
      adsorption capacities were small. Benzene and toluene have very similar
      adsorption isotherms, suggesting the side chain of toluene, i.e., alkyl chain,
      did not have significant effect on its adsorption. The amount of adsorption and
      isotherm slope were in the order of toluene approximately benzene > benzoic acid
      > phenol. The occupation ratios of those organic compounds on the surfaces of FSM
      16 were estimated less than 1%. Solubility of the compounds seems the major
      factor determining their adsorption by FSM-16. Phenol has the highest solubility
      and thus was least adsorbed by FSM-16. In contrast, toluene and benzene have very
      low solubilities and are the most adsorbed ones.

PMID- 15509013
TI  - Hydrogen storage of multi-walled carbon nanotubes obtained by decomposition of
      hydrocarbon over Ni-Li/SiO2.
AB  - Hydrogen storage into multi-walled carbon nanotubes obtained by the decomposition
      of hydrocarbons using Ni-Li/SiO2 was investigated. The optimized reaction
      conditions for the synthesis of carbon nanotubes were 873K and W/F=40 g
      cat.h/mol, and carbon nanotubes obtained by C2H6 decomposition were found to
      exhibit fairly large H2 storage capacity of 1 wt% at room temperature. The
      storage capacity increased with decreasing temperature and a capacity of 5 wt%
      was achieved at 77K, with 66% of adsorbed hydrogen being desorbable. Hydrogen
      adsorption by pi orbital in C-C bond coordination is proposed, observing both
      weakened Raman adsorption C-C peaks and the thermal release of CH4 after H2
      storage.

PMID- 15509014
TI  - Sorption of Co(II), Ni(II), and Zn(II) on biogenic manganese oxides produced by a
      Mn-oxidizing fungus, strain KR21-2.
AB  - The characteristics of Co(II), Ni(II), and Zn(II) sorption on freshly produced
      biogenic Mn oxides by a Mn-oxidizing fungus, strain KR21-2, were investigated.
      The biogenic Mn oxides showed about 10-fold higher efficiencies for sorbing the
      metal ions than a synthetic Mn oxide (gamma-MnO2) on the basis of unit weight and
      unit surface area. The order of sorption efficiency on the biogenic Mn oxides was
      Co(II) > Zn(II) > Ni(II), while that on the synthetic Mn oxide was Zn(II) >
      Co(II) > Ni(II). These sorption selectivities were confirmed by both sorption
      isotherms and competitive sorption experiments. Two-step extraction, using 10mM
      CuSO4 solution for exchangeable sorbed ions and 10-20mM hydroxylamine
      hydrochloride for ions bound to reducible Mn oxide phase, showed higher
      irreversibility of Co(II) and Ni(II) sorption on the biogenic Mn oxides while
      Zn(II) sorption was mostly reversible (Cu(II)-exchangeable). Sorptions of Co(II),
      Ni(II), and Zn(II) on the synthetic Mn oxide were, however, found to be mostly
      reversible. Higher irreversibility of Co(II) and Ni(II) sorption on the biogenic
      Mn oxides may partly explain higher accumulation of these metal ions in Mn oxide
      phases in natural environments. The results obtained in this study raise the
      possibility to applying the biogenic Mn oxide formation to treatment of water
      contaminated with toxic metal ions.

PMID- 15509015
TI  - Natural and modified nanomaterials as sorbents of environmental contaminants.
AB  - Nanotechnology is a revolutionary scientific and engineering concept that will
      have a large impact on our life. A core piece of this technology is the
      production of nanomaterials for electronic, chemical, medical, pharmaceutical,
      and environmental applications. In the last case, natural and modified natural
      nanomaterials would be good reference points for comparison of the functionality,
      cost, and potential ecological implications of synthetic nanomaterials. Here we
      investigated the performance of natural and modified nanomaterials (an allophane
      and a surface-modified smectite) in adsorbing copper (a common heavy metal
      contaminant), naphthalene (a representative polycyclic aromatic hydrocarbon), or
      17beta-estradiol (an endocrine-disrupting chemical). Allophane is an effective
      sorbent of copper (Cu): at pH 5.5 it can take up 4448 mg Cu/kg at the equilibrium
      concentration of 10mg Cu/L. On the other hand, the surface-modified smectite is
      an excellent sorbent for naphthalene and 17beta-estradiol. It can sorb 1180mg
      naphthalene/kg at the equilibrium concentration of 1 mg/L or remove 98% of 17beta
      estradiol from a solution after 4h of reaction. While the environmental impact
      and health effects of synthetic nanomaterials are essentially unknown and their
      use is of concern, natural nanomaterials (e.g., allophane and smectites) have
      been part of human existence since antiquity. As such, they do not pose much risk
      either to the physical environment or to human health.

PMID- 15509016
TI  - Size distribution and characterization of ultrafine particles in roadside
      atmosphere.
AB  - The number concentration and number size distributions of ultrafine particles
      were measured with a Scanning Mobility Particle Sizer (SMPS) at a roadside in
      early autumn and winter, and the results are discussed with regard to the
      contribution of traffic activity and meteorological conditions. The number
      concentration of the <50 nm fraction increased in the morning under calm wind
      conditions, and this increase corresponded with the increase in total traffic
      volume and nitric oxide. The increase in ultrafine particles was influenced not
      only by the increase in total traffic but also by the high contribution of diesel
      engine vehicles. The number concentration decreased around noon as the wind speed
      increased, although the total traffic and the number of diesel engine vehicles
      were at the same level as in the morning. The number size distribution in the
      morning was bimodal, with a first peak diameter of around 30 nm and a second of
      around 90 nm in both periods. The volatility of ultrafine particles was
      investigated using a thermal denuder operating at 250 degrees C. The first peak
      consisted mainly of volatile components, whereas the second one consisted of
      solid materials plus some volatile components. These results were consistent with
      the mass size distribution of elemental and organic carbon. The number size
      distribution with a peak diameter of around 30 nm was also observed in the
      afternoon at a suburban site; however, it was produced not by vehicle emissions
      directly but by photochemical reactions. Although a relatively high number
      concentration was also observed in the morning at the suburban site due to
      vehicle emission, the peak diameter ranged from 40 to 90 nm, which was larger
      than at the roadside.

PMID- 15509017
TI  - Effects of nanophase materials (< or = 20 nm) on biological responses.
AB  - Nanophase materials have enhanced properties (thermal, mechanical, electrical,
      surface reactivity, etc.) not found in bulk materials. Intuitively, the
      enhancement of material properties could occur when the materials encounter
      biological specimens. Previous investigations of biological interactions with
      nanometer-scale materials have been very limited. With the ability to manipulate
      atoms and molecules, we now can create predefined nanostructures with
      unprecedented precision. In parallel with this development, improved
      understanding of the biological effects of the nanophase materials, whatever
      those may be, should also deserve attention. In this study, we have applied
      precision aerosol technology to investigate cellular response to nanoparticles.
      We used synthetic nanoparticles generated by an electrospray technique to produce
      nanoparticles in the size range of 8-13 nm with practically monodispersed aerosol
      particles and approximately the same number concentration. We report here on the
      potency of nano-metal particles with single or binary chemical components in
      eliciting interleukin-8 (IL-8) production from epithelial cell lines. For single
      component nanoparticles, we found that nano-Cu particles were more potent in IL-8
      production than nano-Ni and nano-V particles. However, the kinetics of IL-8
      production by these three nanoparticles was different, the nano-Ni being the
      highest among the three. When sulfuric acid was introduced to form acidified nano
      Ni particles, we found that the potency of such binary-component nanoparticles in
      eliciting IL-8 production was increased markedly, by about six times. However,
      the acidified binary nano-Na and -Mg nanoparticles did not exhibit the same
      effects as binary nano-Ni particles did. Since Ni, a transition metal, could
      induce free radicals on cell surfaces, while Na and Mg could not, the acidity
      might have enhanced the oxidative stress caused by radicals to the cells, leading
      to markedly higher IL-8 production. This result indicates the complexity of
      biological responses to nanoparticles. We believe that the exposure methodology
      and aerosol technology employed in our research will provide an effective means
      to systematically investigate cellular responses to nanoparticles, structured or
      unstructured, in ongoing research projects. Different cell lines, chemicals, and
      particle morphology can also be investigated using such a methodology.

PMID- 15509018
TI  - On the characterization of environmental nanoparticles.
AB  - The presence and release of nanoparticles into the environment has important
      implications for human health and the environment. This article highlights and
      describes techniques that are effective in the characterization of anthropogenic
      and naturally occurring nanoparticles. Particle attributes like size, size
      distribution, shape, structure, microstructure, composition, and homogeneity are
      critically important to determining the potential impact of such materials on
      health and the environment. Many techniques yield data for a collection of
      nanoparticles; while others yield data for individual nanoparticles; and still
      others yield data showing the size, distribution of chemical species, and
      variations in structure and microstructure for a single nanoparticle. All are
      important in the context of environmental nanoparticles. Many of these techniques
      are complementary, and depending on the information required, the ideal
      characterization usually employs multiple techniques.

PMID- 15509019
TI  - Vegetative endocarditis associated with Escherichia coli in a dromedary camel.

PMID- 15509020
TI  - A preliminary trial using multi-target polymerase chain reaction (multiplex PCR)
      and restriction fragment length polymorphism (PCR-RFLP) on the same feedstuffs to
      detect tissues of animal origin.
AB  - A preliminary study using multi-target polymerase chain reaction (multiplex PCR)
      and restriction fragment length polymorphism (PCR-RFLP) was done on the same
      feedstuffs to detect animal tissues. The results of the two methods differ
      somewhat: PCR-RFLP did not detect any signal in any sample, but multiplex PCR
      detected a signal in one sample. These findings could be a basis for further
      investigations.

PMID- 15509021
TI  - Plasma steroid variations in bull calves repeatedly treated with testosterone,
      nortestosterone and oestradiol administered alone or in combination.
AB  - The aim of this work was to investigate the secretion of dehydroepiandrosterone
      (DHEA), testosterone (T), dihydrotestosterone (DHT) and oestradiol (E) as
      biological markers in response to illegal administration of testosterone, 19
      nortestosterone (N) and oestradiol, either alone or in combination. Twenty male
      Friesian calves (age 13-14 months) were allotted to a control group (n = 5), and
      five experimental groups (n = 3) each. Each experimental animal was repeatedly
      injected with one of the following hormonal treatments: E, T, N, T+E and N+E.
      Circulating DHEA, T, DHT and E were determined by radioimmunoassay. The
      administration of T alone did not induce any variation in plasma DHEA, T, DHT and
      E, which were similar to those in the control group. In contrast, DHEA, T and DHT
      were on average significantly lower in the T+E and N-treated groups (p < 0.01),
      whereas the administration of N+E resulted in the reduction of plasma T and DHT
      without any modification of plasma DHEA. The administration of E alone or in
      combination increased circulating levels of E but did not affect androgen plasma
      profiles. The results indicate that plasma levels of T do not permit detection of
      illegal treatments because plasma androgens always remained within the
      physiological range. Illegal E treatment could be detected in blood samples when
      they were collected at least every 20 days.

PMID- 15509023
TI  - Development, survival and availability of gastrointestinal nematodes of sheep on
      pastures in a semi-arid area of Kajiado District of Kenya.
AB  - A study was carried out on a ranch in the semi-arid area of Kajiado District in
      Kenya during the period July 2000 to June 2001 to determine the seasonal patterns
      of development and survival of gastrointestinal nematodes of sheep on pastures. A
      series of plots were contaminated with sheep faeces every month and pasture
      samples were collected weekly for the recovery and identification of larvae. The
      availability of infective larvae on naturally contaminated pastures was also
      monitored on the paddocks grazed by sheep and around the night pen and the
      watering point every month from July 2000 to June 2001. The results from the
      examination of the pasture samples indicated that rainfall distribution was the
      major factor governing the development and survival of the pre-parasitic stages.
      No parasitic larvae were detected from the plots contaminated during the dry
      months from July to October 2000, but development and translocation of infective
      larvae on pastures occurred on plots contaminated during the rainy seasons and
      soon after when relatively high moisture was present in the herbage (November
      2000 to June 2001). During this period, peak larval counts occurred between the
      first and the second week post contamination, then declined to undetectable
      levels between week 4 and 16 post contamination. The lack of development of
      infective larvae during the dry season and the relatively rapid decline of their
      population during the wet season presents an opportunity for the use of pasture
      spelling as a means of helminth control in the study area. The availability of
      infective larvae on naturally contaminated pastures, around the night pen and
      around the watering point also followed the rainfall distribution pattern.
      Infective larvae were consistently recovered around the watering point throughout
      the study period. This indicated that the point is an important source of
      infection for sheep, especially during the dry season when other pastures are non
      infective.

PMID- 15509022
TI  - Total anthelmintic failure to control nematode parasites of small ruminants on
      government breeding farms in Sabah, East Malaysia.
AB  - Government-owned small-ruminant breeding farms in Malaysia provide the source of
      sheep and goats to smallholder farmers in the country. In the eastern Malaysian
      state of Sabah, high-level stock losses have been recorded on these farms for
      several years, frequently accompanied by clinical signs indicating pathogenic
      levels of infections with the nematode parasite Haemonchus contortus. This
      suggests that their dependence on chemotherapy to control parasite infections had
      failed. Accordingly, tests for anthelmintic efficacy using the faecal egg count
      reduction test (FECRT) on the range of drugs used to control nematode parasites
      were carried out on the five government small-ruminant breeding farms in Sabah.
      These tests showed a total failure of the benzimidazole, imidothiazole,
      macrocyclic lactone and salicylanilide groups of anthelmintics to control H.
      contortus infections of sheep and goats on all farms. Drastic changes in animal
      management need to be made in an attempt to deal with this situation, for which
      suggestions are made.

PMID- 15509024
TI  - Quantitative analysis of interleukin-6 expression in porcine spleen cells and
      alveolar macrophages using real-time PCR.
AB  - Interleukin-6 (IL-6), a multifocal cytokine produced by lymphoid and non-lymphoid
      cells, regulates immune responses, acute-phase reactions against bacterial
      infections, and haematopoiesis. After cloning and sequencing of porcine IL-6, the
      expression pattern of porcine IL-6 mRNA was evaluated through real-time RT-PCR
      using porcine immune cells (spleen cells and alveolar macrophages) following
      stimulation with LPS. The sequence has been reported to GenBank with Accession
      no. AF 518322. The nucleotide sequence was different at the 89th and 205th
      positions in comparison with M80258, but only at the 205th with M86722.
      Comparison of porcine IL-6, Accession no. AF 518322, with IL-6 of human, canine,
      ovine, and mouse showed homologies of 78%, 81%, 82% and 73% in nucleotide
      sequence and 42%, 69%, 61% and 42% in amino acids. Expression of IL-6 mRNA was
      induced by stimulation with LPS. IL-6 mRNA expression in alveolar macrophages
      peaked at 2 h and decreased sharply to control levels at 4 h, whereas it peaked
      at 14 h and decreased at 24 h in spleen cells after stimulation with LPS (1
      microg/ml). These results suggest that IL-6 mRNA expression in porcine immune
      cells is cell-type specific and the results of this study could be used as the
      basis for research on the porcine immune system.

PMID- 15509025
TI  - Pharmacokinetics and bioavailability of florfenicol following intravenous,
      intramuscular and oral administrations in rabbits.
AB  - This study examined the disposition kinetics and bioavailability of florfenicol
      after intravenous (i.v.), intramuscular (i.m.) and oral administration to rabbits
      at a dose of 30 mg/kg BW. Serial blood samples were collected through an
      indwelling catheter intermittently for 24 h for various routes. Plasma
      antibacterial concentrations were determined using a microbiological assay method
      with Bacillus subtilis ATCC 6633 as a reference organism. Plasma concentration
      time data generated in the present study were analysed by non-compartmental
      methods based on statistical moment theory. Following i.v. administration, the
      overall elimination half-life (t1/2beta) was 1.54 h, mean residence time (MRT)
      was 1.69 h, mean volume of distribution at steady-state (Vdss) was 0.57 L/kg, and
      total body clearance (Cltot) was 0.34 L/kg/h. After i.m. and oral dosing, the
      terminal part of the curve should correspond to the absorption phase, instead of
      to the elimination phase, with terminal half-lives of 3.01 and 2.57 h,
      respectively. The mean absorption time (MAT) was 2.65 h for i.m. and 2.01 h for
      oral administration. Elimination rate constants differed with i.v., i.m. and oral
      administrations, suggesting a flip-flop situation. The observed mean peak plasma
      concentrations (Cmax obs) were 21.65 and 15.14 microg/ml achieved at a post
      injection time (Tmax obs) of 0.5 h following i.m. and oral dosing, respectively.
      The absolute systemic availabilities were 88.25% and 50.79%, respectively, and
      the extent of plasma protein binding percent was 11.65%.

PMID- 15509026
TI  - Pharmacokinetics and pharmacodynamics of dexamethasone after intravenous
      administration in camels: effect of dose.
AB  - The pharmacokinetics and pharmacodynamics of dexamethasone were evaluated in
      healthy camels after single intravenous bolus doses of 0.05, 0.1 and 0.2 mg/kg
      body weight. Dexamethasone showed dose-independent pharmacokinetics. The
      pharmacokinetic parameters of the two-compartment pharmacokinetic model for the
      lowest intravenous dose (mean+/-SD) were as follows: terminal elimination half
      life 8.17 +/- 1.79 h; total body clearance 100.7 +/- 52.1 (ml/h)/kg; volume of
      distribution at steady state 0.95 +/- 0.23 L/kg; and volume of the central
      compartment 0.22 +/- 0.07 L/kg. The extent of plasma protein binding was linear
      over the concentration range 5-100 ng/ml and averaged 75% +/- 2%. Pharmacodynamic
      effects were evaluated by measuring endogenous plasma cortisol concentrations,
      numbers of circulating lymphocytes and neutrophils and plasma glucose
      concentrations and were analysed using indirect pharmacokinetic/pharmacodynamic
      models. The cumulative systemic effect increased with dose for markers of
      pharmacodynamic activity. The estimated IC50 of dexamethasone for cortisol and
      lymphocytes for the lowest dose were 3.74 +/- 2.44 and 5.58 +/- 8.37 ng/ml,
      respectively and the EC50 values for neutrophils and glucose were 45.8 +/- 36.9
      and 1.17 +/- 0.71 ng/ml, respectively.

PMID- 15509027
TI  - Partial antigenic characterization of buffalopox virus.
AB  - The present study was undertaken to antigenically characterize the buffalopox
      virus (BPV). Six monoclonal antibodies (MAbs) against the BP4 strain of BPV have
      been produced and characterized. All six MAbs appeared to be specific to BPV, as
      none of them showed cross-reactivity with other poxviruses in antigen capture
      ELISA. Only two MAbs (20AB8 and 20CD11) bound significantly with different BPV
      isolates in antigen capture ELISA, whereas the remaining four MAbs bound weakly
      with the BPV. In Western blot analysis with purified BPV-BP4, the rabbit
      hyperimmune serum against purified BPV-BP4 reacted with 15 immunodominant
      polypeptides (100 kDa to 25 kDa), whereas two MAbs (21CB6, 21DB11) reacted with
      42 kDa and 45 kDa polypeptides, respectively. However, three MAbs (20AB8, 20CD11,
      21CB5) reacted with three degraded polypeptides (100 kDa, 40 kDa and 87 kDa) of
      BPV-BP4. In radioimmunoprecipitation assay (RIPA) with the rabbit hyperimmune
      serum to BPV-BP4, three virus specific polypeptides (69 kDa, 34 kDa, 32 kDa) were
      recognized in BPV-BP4, whereas two polypeptides (69 kDa, 34 kDa) were recognized
      in other BPV isolates (BPV-Bly, BPV-Vij96, BPV-Vij97). In virus neutralization
      test, none of the six MAbs tested showed any significant neutralizing ability to
      infection with different BPV isolates. However, the hyperimmune serum showed weak
      neutralizing ability to BPV infection.

PMID- 15509030
TI  - Palliative philosophy--a missing element in holistic ESRD care.

PMID- 15509029
TI  - Pain management at the end of life in a patient with renal failure.
AB  - Literature indicates that an essential element of a 'good' death is the absence
      of pain. Achieving a pain-free death for the patient who discontinues dialysis is
      a goal shared by patient, family and care providers. Pain management at end of
      life can be challenging, especially in the setting of renal failure. Aspects of
      assessment and pharmacological management of pain in the dying patient are
      explored through the use of a case study. Through investment in ongoing
      relationships with their patients, and striving to build knowledge and skills in
      pain management, nephrology nurses promote excellence in end-of-life patient
      care.

PMID- 15509032
TI  - Memory tea.

PMID- 15509031
TI  - Comfort coaching.

PMID- 15509033
TI  - Medication considerations in end-of-life care.

PMID- 15509034
TI  - Encouraging the use of advanced directives in the dialysis population.

PMID- 15509035
TI  - Technologists/Technicians participate in end-of-life care.

PMID- 15509036
TI  - Veteran nurses give patients a quick look to avoid waits.

PMID- 15509037
TI  - Overall care of cardiac patients improves with use of pre-printed orders,
      coordination program.
AB  - Performance on the Joint Commission's core measures for heart failure and acute
      myocardial infarction at hospitals in the Legacy Health System, Portland, OR, has
      increased significantly due to a project that encouraged physicians to make
      greater use of pre-printed orders and implementation of a cardiac care
      coordination program.

PMID- 15509038
TI  - Guideline urges reduced use of antibiotics after surgery.
AB  - Surgery patients should receive antibiotics no more than one hour before surgery,
      and for no more than 24 hours after surgery, according to a new consensus
      guideline on surgical infection prevention endorsed by more than 20 medical
      societies and national health care organizations.

PMID- 15509039
TI  - Eye care practice uses physician measurement strategies to achieve CQI.
AB  - When Jeffrey L. Kegarise, OD, purchased Franklin, TN-based Cool Springs Eye Care
      four years ago, the established practice was "a ship that was already moving in
      the right direction," he recalls. But even the most seaworthy vessel needs a
      steady hand to stay the course--a task Kegarise has undertaken with relish by
      implementing across-the-board performance measurement standards.

PMID- 15509040
TI  - Five principles can encourage organizations to 'think lean'.
AB  - Five principles can encourage organizations to think lean. With global
      competitive pressures increasing, more and more manufacturers are using the
      principles of "lean thinking" to trim waste and improve quality in their
      operations. Health care organizations that want to improve performance can borrow
      these principles, which are readily adaptable to the hospital or physician
      practice setting.

PMID- 15509041
TI  - [Proof of the pharmacodynamic activity of Flector Plaster in healthy volunteers
      and patients suffering from osteo-arthritis of the knee].
AB  - STUDY OF HEALTHY VOLUNTEERS: This double blind study (bioadhesive plaster of
      diclofenac epolamine versus placebo), showed that the application of diclofenac
      epolamine for 24 hours induced a selective hypoanalgesic effect on the muscle,
      proportional to the degree of hypersensitivity to the pain observed in baseline
      conditions. The enhanced effect on the hyperalgic muscle can be explained by the
      direct impact of the active ingredient on the nociceptors and/or its inhibiting
      effect on the local production of prostaglandins. STUDY OF PATIENTS SUFFERING
      FROM BILATERAL OSTEO-ARTHRITIS OF THE KNEE: In a 24 hour trial of the treatment
      (bioadhesive plaster impregnated with diclofenac epolamine (Flector Plaster)
      versus placebo), the active treatment had a significant impact on the spontaneous
      pain during rest that was enhanced during mouvement. In a longer term trial (72
      hours), the regression of the spontaneous pain on the visual analog scale
      appeared even more significant, still lasting 96 hours after withdrawal of the
      plaster, not only at rest but also on mouvement.

PMID- 15509042
TI  - [Assessment of a topical NSAIDs in the treatment of pain and inflammation. The
      example of Flector Plaster, a local bioadhesive plaster containing diclofenac
      epolamine].
AB  - ADVANTAGES AND INCONVENIENCIES OF TRANSDERMAL SYSTEMS: Regarding the advantages,
      one notes the reduction or even suppression of the gastro-intenstinal disorders
      related to the oral administration of non-steroidal anti-inflammatories (NSAIDs),
      the absence of first pass hepatic effect and the better control of the quantities
      administered of a strong acting drug. Regarding the inconveniencies, one should
      bear in mind the impossibility of administering or the diffusion of high doses of
      irritant or sensitizing molecules on the skin. A preparation for application on
      the skin must be both hydrophilic and lipophilic, with great solubility in water
      and affinity for the lipids, as is the case with diclofenac epolamine. FROM AN
      EXPERIMENTAL POINT OF VIEW: Diclofenac epolamine has demonstrated a strong anti
      inflammatory effect in the rat or the rabbit, with transfer following repeated
      local applications, measurable concentrations in the plasma and adjacent tissues,
      excellent general tolerance and the safety of the plaster. VARIOUS CLINICAL
      TRIALS: Have shown that the Flector Plaster is well tolerated and effective in
      the treatment of epicondylitis, sprained ankles, minor sport-induced trauma and
      osteo-arthrosis of the knee.

PMID- 15509043
TI  - [Social aspects of addiction to smoking].

PMID- 15509044
TI  - [Psychosocial distress and stressful life antecedents associated with smoking. A
      survey of subjects consulting a preventive health center].
AB  - BACKGROUND: The relationship between smoking and various socio-demographic or
      socio-economic factors, as well as the interactions between depressive mood and
      smoking are already known. However, the respective contribution of psychological
      factors and stressful life antecedents during childhood and adolescence warrants
      further specification. METHODS: 2315 consecutive subjects, aged 16 to 59,
      consulting for a free work-up in a preventive health centre, supported by the
      National French Health insurance system, were invited to fill out a series of
      questionnaires: the GHQ-28 and the LOT, respectively measuring psychosocial
      distress and dispositional optimism, as well as a questionnaire on socio
      demographic, socio-economic and biographical data. RESULTS: 78.1% complete
      records could be analysed: the "smokers" group (n = 870, 48.1%) declared a
      current tobacco consumption of at least one cigarette/day. This group was
      characterized by a predominance of male subjects, older age, modest educational
      level, low income level and responded to socio-economic criteria of
      precariousness more frequently (p < 0.001, except for age: p = 0.006). Smoking
      was also associated with higher levels of psychosocial distress, as assessed by
      GHQ-28, especially for the depressive mood and anxiety items of the questionnaire
      (p < 0.001), and with lower levels of dispositional optimism (p < 0.01). As
      regards biographical data, smokers were characterized by a way of life marked by
      financial problems, reduced social contacts, and a higher frequency, before the
      age of 18, of divorce or separation of the parents (p = 0.002), frequent parental
      quarrels (p < 0.001) or separation from the parents (p < 0.001). The presence of
      a depressive mood at GHQ-28 as well as frequent parental quarrels remained
      independent risk factors for smoking in multiple logistic regression (odds ratio
      respectively equal to 1.61 and 1.34), after adjustment on gender, educational
      level and the notion of socio-economic precariousness. CONCLUSION: These results
      highlight the complementary role of socio-economic, psychological factors and
      certain stressful life antecedents among the determinants of smoking and should
      be taken into account for tailoring smoking cessation programs.

PMID- 15509045
TI  - [Influence of doctors' smoking habits on minimal advice for smoking cessation. A
      survey of 369 general practitioners in the department of Vienne, France].
AB  - INTRODUCTION: French doctors' smoking habits may interfere with the effectiveness
      of smoking prevention measures and particularly when providing minimal advice.
      OBJECTIVES: To assess the smoking habits of general practitioners in the
      department of Vienne, France, and to study how they affect minimal advice for
      smoking cessation. METHOD: 257 general practitioners took part in a phone survey
      (26.5%) or answered a written questionnaire (73.5%). The questions bore on socio
      demographic characteristics, smoking habits and the of minimal advice provided
      whether partial or whole. Do you smoke? If so, have you ever thought of quitting?
      RESULTS: The participation rate was 70%. 26% of the participants were current
      smokers--16 % regular smokers, 10% infrequent smokers, 30% had quit and 44% had
      never smoke. 44.4% investigated smoking habits as a matter of course, and 41%
      provided intensive advice for smoking cessation. Doctors who had never smoked
      gave more advice than those who currently smoked or had quit. DISCUSSION: A
      comparison with former studies reveals that the number of doctors who smoke has
      decreased. However, minimal intervention on smoking cessation is put into
      practice by less than half of the doctors. CONCLUSION: The incidence of smoking
      among doctors in the Department of Vienne remains too high and minimal
      intervention on smoking cessation is still insufficient. However, doctors who had
      never smoked provided minimal advice more often than those who currently smoked
      or had quit.

PMID- 15509046
TI  - [Maternal pancytopenia during antenatal treatment of congenital toxoplasmosis].
AB  - INTRODUCTION: The treatment of reference of congenital toxoplasmosis combines two
      folate synthesis inhibitors, pyrimethamine and an antibacterial sulfamide
      (sulfadiazine or sulfadoxine). Despite the efficacy of this combination, the
      possibility of eventually severe side effects must also be taken into account.
      OBSERVATION: A pancytopenia occurred at 37 weeks of amenorrhea during antenatal
      treatment for congenital toxoplasmosis in a tripara. The outcome was positive
      following administration of strong doses of parenteral folinic acid combined with
      platelet transfusion and broad-spectrum antibiotics. DISCUSSION: Each of the
      molecules (pyrimethamine and antibacterial sulfamide) used for the treatment of
      congenital toxoplasmosis can lead to acute haematological problems. The
      occurrence of maternal pancytopenia however remains exceptional. It is
      principally related to pyrimethamine and is usually observed in the presence of
      factors enhancing folate deficiency.

PMID- 15509047
TI  - [Acute episode of psychosis during hospitalisation in a medical intensive care
      unit].
AB  - INTRODUCTION: Psychiatric disorders are frequently reported in intensive care
      units (ICU). The occurrence of an acute psychotic decompensation in a patient
      opens the debate with several hypotheses. CASE REPORT: A primary episode of acute
      psychotic decompensation occurred in a 27 year-old woman during hospitalisation
      in an intensive care unit due to attempted suicide following ingestion of
      propanolol and bronazepam. DISCUSSION: Factors of stress can contribute to the
      onset of acute psychotic decompensation. The influence of pharmacological
      products can also explain the latter because of the iatrogenics of molecules
      ingested purposefully, but also the eventual responsibility of the treatments
      used in resuscitation. According to one hypothesis, a certain quantity of
      dopamine in this patient could have passed into the central nervous system that
      benefited from an alteration in the permeability of the haematoencephalic barrier
      secondary to severe hypoperfusion.

PMID- 15509048
TI  - [Thrombosis of the right ovarian vein].
AB  - INTRODUCTION: Thrombosis of the ovarian vein (TOV) is a rare complication which
      arises classically in the post-partum. Its main signs are pain in the flanks or
      the iliac fossa, associated with temperature and hyperleukocytosis. It is a
      differential diagnosis of acute appendicitis when located on the right side.
      OBSERVATION: A 26 year-old, primiparous woman consulted at 38 weeks of
      amenorrhoea for pain in the right iliac fossa and flank with a temperature of
      38.6 degrees C. Three days after delivery, because of heavier pain, a coelioscopy
      was decided on that led to the diagnosis of thrombosis of the right ovarian vein.
      COMMENTS: Improvement in the diagnosis techniques, notably Doppler
      ultrasonography and spiral CT should avoid the diagnosis of TOV during surgery.
      Traditionally a post-partum complication, TOV can occur before delivery, period
      during which it is very important not to misjudge this diagnosis, notably in case
      of thrombosis spreading to the inferior vena cava with free-floating thrombus.
      The treatment of TOV is essentially medical. In the case of extension to the vena
      cava, the installation of a vena cava filter or a surgical cava thrombectomy may
      be necessary.

PMID- 15509049
TI  - [Cannabis-induced toxicity in an 11 month-old child].

PMID- 15509050
TI  - [Nosocomial pneumonia due to resistant Enterobacter aerogenes].

PMID- 15509051
TI  - [From food poisoning to hypovitaminosis C].

PMID- 15509052
TI  - [Pneumatocele, a rare complication of bronchopneumopathy].

PMID- 15509053
TI  - [Pulmonary alveolar microlithiasis].

PMID- 15509054
TI  - [The significance and treatment of antiphospholipid antibodies].
AB  - ANTIBODIES: The term antiphospholipid antibodies (APLA) regroups a family
      antibodies that recognise anionic and neutral phospholipids, which are the
      components of plasmatic cell membranes. These antibodies expose the patients to
      risk of venous and/or arterials thromboembolic accidents and obstetrical
      complications such as repeated early miscarriage or, more rarely foetal loss. A
      SYNDROME: The presence of such antibodies associated with this type of clinical
      events defines the antiphospholipid antibody syndrome (APS) that can be isolated
      and defined as primary or associated with systemic lupus erythematosus. The APS
      represents one of the most frequent thrombophilic states. The two APLA used in
      the diagnosis of APS are the circulating lupus anticoagulant and anticardiolipid
      antibodies. Indeed, these are the only APS for which research techniques have
      been standardised. PERSONALISED TREATMENT: Treatment relies on anticoagulants.
      Steroids are unnecessary except when APS is associated with lupus during the
      catastrophic syndrome of APS, characterised by multiorgan failure related to
      thrombotic microangiopathy lesions. The modalities of use of anticoagulants
      (indications, dose and duration) remain debated and underline the great risk of
      recurrent thrombosis on withdrawal of treatment.

PMID- 15509055
TI  - [The application of digestive endoscopic ultrasonography in the gallbladder
      pathology].
AB  - A WELL DEFINED PATHOLOGY: Bilary lithiasis and vesicular parietal abnormalities
      constitute the totality of the gallbladder pathology. The surgical experience and
      widely current use of digestive imaging, notably ultrasonography, have
      contributed to enlightening our knowledge of this pathology. POTENTIAL DIAGNOSTIC
      PROBLEMS: There is no particular problem in the diagnosis of gallbladder
      lithiasis and its treatment is currently codified. However the discovery of
      thickened gallbladder wall or polyps increases the fear of gallbladder cancer. A
      FUNDAMENTAL ROLE FOR ENDOSCOPIC ULTRASONOGRAPHY: Within the framework of
      screening for cancer, endoscopic ultrasonography, the performance of which in
      gallbladder pathology has rarely been studied, appears promising. Other than its
      role in the control of the extension of gallbladder cancers, it provides reliable
      characterisation of most of the polyps. Hence its place today is unavoidable in
      the therapeutic decision trees of such affections.

PMID- 15509056
TI  - [Pancreatic islet transplantation, results, techniques, perspectives and
      indications].
AB  - THE SITUATION: Islet transplantation stands as a promising curative treatment for
      type 1 diabetes. Improvements of this still experimental procedure were recently
      obtained through the modification of the immunosuppressive regimen and the
      increase of the islet mass delivered to the patient. Several centers have now
      reported rates of insulin-independence of 80% and beyond after one year, although
      these cohorts of patients are limited, and the results restricted to experienced
      centers. TECHNICAL ASPECTS: Islet isolation relies upon enzymatic digestion of
      the pancreas, transplantation is peformed through transhepatic portal vein
      catheterism, a strong steroid-free immunosuppression is needed. LIMITATIONS:
      Immune rejection and recurrence of diabetic autoimmunity are major obstacles,
      requiring a potentially harmful immunosuppression. Viability of pancreatic islets
      must be improved, since over 50% of cells are non specifically destroyed after
      their injection. The reproducibility of the islet isolation procedure is
      insufficient. The major question is the optimal source of tissue, as pancreas
      donors are scarce. INDICATIONS: Islet transplantation is now considered not only
      for patients needing immunosuppression for another transplantation (most often
      kidney), but also for patients with labile diabetes, recurrent life-threatening
      hypoglycemia or ketoacidosis, responsible for severe deterioration of the quality
      of life. CONCLUSION: In order to reduce the waiting lists of diabetic patients
      and to improve benefits/risks of the process, progress is required in the fields
      of organisational strategy, immunomodulation, and research on adult and embryonic
      stem cells.

PMID- 15509057
TI  - [Percutaneous closure of the inter-auricular communications, well defined
      indications].
AB  - POSSIBLITIES FOR PROGNOSTIC IMPROVEMENT: The inter-auricular communication (IAC)
      is the most frequent of congential malformations in adults and is responsible for
      enhanced morbidity and rduction in life expectancy. The closure of an IAC with
      volumic overload eradicates such morbidity and mortality. The technical progress
      in the conception of prosthesises that obstrue the interauricular communications
      via the percutaneous route make this technique a reliable alternative to surgery
      that, itself, leads to a certain degree of discomfort and considerable morbidity.
      DEPENDING ON THE ECHOCARDIOGRAPHICAL DATA: The selection of patients is crucial
      and relies on trans-thoracic echocardiography. It is indicated in isolated ostium
      secundum-type inter-auricular communications with a border of at least 4 mm
      separating it from the adjacent structures of the heart; the size on the
      echocardiography must not exceed 30 mm. FROM A TECHNICAL POINT OF VIEW: The
      closure is made under fluoroscopic and echocardiographic control via the trans
      oesophageal route. It is rapid, simple, and induces a low rate of morbidity. With
      Amplatz's prosthesis, the percentage of complete closure is equivalent to that
      obtained with surgery but with less morbidity with regard to arrhythmia. Today
      the reliable percutaneous closure of an IAC will probably permit the extension of
      the indications for the closure of this congenital abnormality in adults.

PMID- 15509058
TI  - [Regarding Kawasaki's disease in adults].

PMID- 15509059
TI  - [The traveller's diarrhoea (2/2)--treatment].

PMID- 15509060
TI  - Characterization of cardiovascular liver motion for the eventual application of
      elasticity imaging to the liver in vivo.
AB  - Elastography, which uses ultrasound to image the tissue strain that results from
      an applied displacement, can display tumours and heat-ablated tissue with high
      contrast. However, its application to liver in vivo may be problematic due to the
      presence of respiratory and cardiovascular sources of displacement. The aim of
      this study was to measure the cardiovascular-induced component of natural liver
      motion for the purpose of planning future work that will either use the motion to
      produce elasticity images or will compensate for it when employing an external
      source of displacement. A total of 36 sequences of 7 s real-time radio frequency
      (RF) echo images of the liver were acquired from six healthy volunteers during
      breath-hold using a stationary 3.5 MHz transducer. For each image sequence, the
      axial and lateral components of displacement were measured for each pair of
      consecutive RF images using 2D-echo tracking. The spatio-temporal character of
      these displacements was then analysed using a novel approach, employing proper
      orthogonal decomposition, whereby the dominant motion patterns are described by
      eigenvectors with the highest eigenvalues. The motion patterns of different liver
      segments were complex, but they were also found to be cyclic, highly repeatable
      and capable of producing measurable displacements in the liver. These
      observations provide good evidence to suggest that it may be possible to correct
      for natural liver motion when using an externally applied displacement for
      elasticity imaging. It was also found that about 65%-70% of all liver motion
      could be described using the first eigenvector. Use of only this component of the
      motion will greatly simplify the design of a mechanical system to be used in an
      objective study of elasticity imaging of phantoms and excised tissues in the
      presence of simulated cardiovascular-induced liver motion.

PMID- 15509061
TI  - Viscoelastic characterization of in vitro canine tissue.
AB  - Mechanical properties of biological tissues are of interest for assessing the
      performance of elastographic methods that evaluate the stiffness characteristics
      of tissue. The mechanical properties of interest include the frequency-dependent
      complex moduli, storage and loss moduli of tissues. Determination of the
      mechanical properties of biological tissues is often limited by proper geometry
      of the sample, as well as homogeneity of the stress-strain relationship.
      Measurements were performed on in vitro canine liver tissue specimens, over a
      frequency range from 0.1 to 400 Hz. Tests were conducted using an EnduraTEC ELF
      3200, a dynamic testing system for determining the mechanical properties of
      materials. Both normal tissues and thermal lesions prepared by radio frequency
      ablation were tested. Experiments were conducted by uniaxially compressing tissue
      samples using Plexiglas platens larger than the specimens and measuring the load
      response. The resulting moduli spectra were then fit to a modified Kelvin-Voigt
      model, called the Kelvin-Voigt fractional derivative model. The data agree well
      with the model and in comparing the results from the normal tissue with that of
      the thermal lesions, the concept of a complex modulus contrast is introduced and
      its applications to elastography are discussed.

PMID- 15509062
TI  - Tolerance to missing data using a likelihood ratio based classifier for computer
      aided classification of breast cancer.
AB  - While mammography is a highly sensitive method for detecting breast tumours, its
      ability to differentiate between malignant and benign lesions is low, which may
      result in as many as 70% of unnecessary biopsies. The purpose of this study was
      to develop a highly specific computer-aided diagnosis algorithm to improve
      classification of mammographic masses. A classifier based on the likelihood ratio
      was developed to accommodate cases with missing data. Data for development
      included 671 biopsy cases (245 malignant), with biopsy-proved outcome. Sixteen
      features based on the BI-RADS lexicon and patient history had been recorded for
      the cases, with 1.3 +/- 1.1 missing feature values per case. Classifier
      evaluation methods included receiver operating characteristic and leave-one-out
      bootstrap sampling. The classifier achieved 32% specificity at 100% sensitivity
      on the 671 cases with 16 features that had missing values. Utilizing just the
      seven features present for all cases resulted in decreased performance at 100%
      sensitivity with average 19% specificity. No cases and no feature data were
      omitted during classifier development, showing that it is more beneficial to
      utilize cases with missing values than to discard incomplete cases that cannot be
      handled by many algorithms. Classification of mammographic masses was commendable
      at high sensitivity levels, indicating that benign cases could be potentially
      spared from biopsy.

PMID- 15509063
TI  - Statistical list-mode image reconstruction for the high resolution research
      tomograph.
AB  - We have investigated statistical list-mode reconstruction applicable to a depth
      encoding high resolution research tomograph. An image non-negativity constraint
      has been employed in the reconstructions and is shown to effectively remove the
      overestimation bias introduced by the sinogram non-negativity constraint. We have
      furthermore implemented a convergent subsetized (CS) list-mode reconstruction
      algorithm, based on previous work (Hsiao et al 2002 Conf. Rec. SPIE Med. Imaging
      4684 10-19; Hsiao et al 2002 Conf. Rec. IEEE Int. Symp. Biomed. Imaging 409-12)
      on convergent histogram OSEM reconstruction. We have demonstrated that the first
      step of the convergent algorithm is exactly equivalent (unlike the histogram-mode
      case) to the regular subsetized list-mode EM algorithm, while the second and
      final step takes the form of additive updates in image space. We have shown that
      in terms of contrast, noise as well as FWHM width behaviour, the CS algorithm is
      robust and does not result in limit cycles. A hybrid algorithm based on the
      ordinary and the convergent algorithms is also proposed, and is shown to combine
      the advantages of the two algorithms (i.e. it is able to reach a higher image
      quality in fewer iterations while maintaining the convergent behaviour), making
      the hybrid approach a good alternative to the ordinary subsetized list-mode EM
      algorithm.

PMID- 15509064
TI  - The separation of the head and phantom scatter components from a phase space
      description.
AB  - The formalism based on phantom and collimator scatter factors for high energy
      photon beams is deduced using a phase space description. The phantom scatter
      factors (Sp) depend on the field size and shape at the level of the phantom and
      are generally considered independent of the collimation details used to form the
      desired field provided the effect of contaminant electrons can be neglected. As
      demonstrated in this work, this behaviour leads to the applicability of the
      Clarkson method in irregular fields. However, for a given field formed with a
      tertiary collimator it is not a priori clear that the variations of extrafocal
      radiation due to secondary collimator setting do not affect the phantom scatter
      correction factors. In fact, the extrafocal radiation has a lower mean energy
      than that of unscattered photons, and this radiation can reach points well
      outside the radiation field increasing the irradiated phantom volume. Besides,
      transmission through the blocks contributes to phantom scatter. Therefore, for a
      given block-defined field, the associated phantom scatter dose, per unit of
      fluence in air on the central axis, should in principle increase when enlarging
      the secondary collimator field. To confirm this, isocentric Sp data for 6 MV
      photons were measured at 10 cm depth in water, reducing with cerrobend blocks
      several fields formed with the secondary collimators. In particular, when a 30 x
      30 cm2 collimator field is reduced with blocks to a 7 x 7 cm2 field, the dose per
      unit of fluence in air is 1.4% higher than that of the square collimator field
      equating the given block field. Our calculations indicate that in this case the
      block transmission accounts for only 0.2% of this increment, showing that the
      remaining effect is due to extrafocal radiation. As a concluding remark, this
      work contributes to a better understanding of the classical Clarkson method for
      irregular fields giving, additionally, a formal interpretation of the commonly
      used quantities.

PMID- 15509065
TI  - A parameter study to determine the optimal source neutron energy in boron neutron
      capture therapy of brain tumours.
AB  - The values of the parameters used in boron neutron capture therapy (BNCT) to
      calculate a given dose to human tissue vary with patients due to different
      physical, biological and/or medical circumstances. Parameters include the tissue
      dimensions, the 10B concentration and the relative biological effectiveness (RBE)
      factors for the different dose components associated with BNCT. Because there is
      still no worldwide agreement on RBE values, more often than not, average values
      for these parameters are used. It turns out that the RBE-problem can be
      circumvented by taking into account all imaginable parameter values. Approaching
      this quest from another angle: the outcome will also provide the parameters (and
      values) which influence the optimal source neutron energy. For brain tumours it
      turns out that the 10B concentration, the RBE factors for 10B as well as fast
      neutrons, together with the dose limit set for healthy tissue, affect the optimal
      BNCT source neutron energy. By using source neutrons of a few keV together with
      neutrons of a few eV, it ensures that, under all imaginable circumstances, a
      maximum of alpha (and lithium) particles can be delivered in the tumour.

PMID- 15509066
TI  - Performance measurements of a depth-encoding PET detector module based on
      position-sensitive avalanche photodiode read-out.
AB  - We are developing a high-resolution, high-efficiency positron emission tomography
      (PET) detector module with depth of interaction (DOI) capability based on a
      lutetium oxyorthosilicate (LSO) scintillator array coupled at both ends to
      position-sensitive avalanche photodiodes (PSAPDs). In this paper we present the
      DOI resolution, energy resolution and timing resolution results for complete
      detector modules. The detector module consists of a 7 x 7 matrix of LSO
      scintillator crystals (1 x 1 x 20 mm3 in dimension) coupled to 8 x 8 mm2 PSAPDs
      at both ends. Flood histograms were acquired and used to generate crystal look-up
      tables. The DOI resolution was measured for individual crystals within the array
      by using the ratio of the signal amplitudes from the two PSAPDs on an event-by
      event basis. A measure of the total scintillation light produced was obtained by
      summing the signal amplitudes from the two PSAPDs. This summed signal was used to
      measure the energy resolution. The DOI resolution was measured to be 3-4 mm FWHM
      irrespective of the position of the crystal within the array, or the interaction
      location along the length of the crystal. The total light signal and energy
      resolution was almost independent of the depth of interaction. The measured
      energy resolution averaged 14% FWHM. The coincidence timing resolution measured
      using a pair of identical detector modules was 4.5 ns FWHM. These results are
      consistent with the design goals and the performance required of a compact, high
      resolution and high-efficiency PET detector module for small animal and breast
      imaging applications.

PMID- 15509067
TI  - Lutetium oxyorthosilicate block detector readout by avalanche photodiode arrays
      for high resolution animal PET.
AB  - Avalanche photodiodes (APDs) have proven to be useful as light detectors for high
      resolution positron emission tomography (PET). Their compactness makes these
      devices excellent candidates for replacing bulky photomultiplier tubes (PMTs) in
      PET systems where space limitations are an issue. The readout of densely packed,
      10 x 10 lutetium oxyorthosilicate (LSO) block detectors (crystal size 2.0 x 2.0 x
      12 mm3) with custom-built monolithic 3 x 3 APD arrays was investigated. The APDs
      had a 5 x 5 mm2 active surface and were arranged on a 6.25 mm pitch. The dead
      space on the edges of the array was 1.25 mm. The APDs were operated at a bias
      voltage of approximately 380 V for a gain of 100 and a dark current of 10 nA per
      APD. The standard deviation in gain between the APDs in the array ranged from 1.8
      to 6.5% as the gain was varied from 50 to 108. A fast, low-noise, multi-channel
      charge sensitive preamplifier application-specific integrated circuit (ASIC) was
      developed for the APD readout. The amplifier had a rise time of 8 ns, a noise
      floor of 515 e- rms and a 9 e- pF(-1) noise slope. An acquired flood image showed
      that all 100 crystals from the block detector could be resolved. Timing
      measurements with single-channel LSO-APD detectors, as well as with the array,
      against a plastic scintillator and PMT assembly showed a time resolution of 1.2
      ns and 2.5 ns, respectively. The energy resolution measured with a single 4.0 x
      4.0 x 10 mm3 LSO crystal, wrapped in four-layer polytetrafluoroethylene (PTFE)
      tape and coupled with optical grease on a single APD of the array, yielded 15%
      (full width at half maximum, FWHM) at 511 keV. Stability tests over 9 months of
      operation showed that the APD arrays do not degrade appreciably. These results
      demonstrate the ability to decode densely packed LSO scintillation blocks with
      compact APD arrays. The good timing and energy resolution makes these detectors
      suitable for high resolution PET.

PMID- 15509068
TI  - Experimental validation of a rapid Monte Carlo based micro-CT simulator.
AB  - We describe a newly developed, accelerated Monte Carlo simulator of a small
      animal micro-CT scanner. Transmission measurements using aluminium slabs are
      employed to estimate the spectrum of the x-ray source. The simulator
      incorporating this spectrum is validated with micro-CT scans of physical water
      phantoms of various diameters, some containing stainless steel and Teflon rods.
      Good agreement is found between simulated and real data: normalized error of
      simulated projections, as compared to the real ones, is typically smaller than
      0.05. Also the reconstructions obtained from simulated and real data are found to
      be similar. Thereafter, effects of scatter are studied using a voxelized software
      phantom representing a rat body. It is shown that the scatter fraction can reach
      tens of per cents in specific areas of the body and therefore scatter can
      significantly affect quantitative accuracy in small animal CT imaging.

PMID- 15509069
TI  - On the origin of speckle in x-ray phase contrast images of lung tissue.
AB  - Phase contrast x-ray imaging of small animal lungs reveals a speckled intensity
      pattern not seen in other tissues, making the lungs highly visible in comparison
      to other organs. Although bearing a superficial resemblance to alveoli, the cause
      of this speckle has not been established. With a view to determining the
      mechanism for the formation of speckle, this paper details the results of
      propagation-based phase contrast experiments performed on mice lungs, together
      with packed glass microspheres used to emulate lung tissue. These experimental
      studies are compared to numerical simulations, based on wave propagation
      techniques. We find that speckle arises from focusing effects, with multiple
      alveoli acting as aberrated compound refractive lenses. Both experiments and
      modelling suggest that this speckle-formation phenomenon may lead to better
      screening methods for human lungs than conventional radiography.

PMID- 15509070
TI  - A unified analysis of FBP-based algorithms in helical cone-beam and circular cone
      and fan-beam scans.
AB  - A circular scanning trajectory is and will likely remain a popular choice of
      trajectory in computed tomography (CT) imaging because it is easy to implement
      and control. Filtered-backprojection (FBP)-based algorithms have been developed
      previously for approximate and exact reconstruction of the entire image or a
      region of interest within the image in circular cone-beam and fan-beam cases.
      Recently, we have developed a 3D FBP-based algorithm for image reconstruction on
      PI-line segments in a helical cone-beam scan. In this work, we demonstrated that
      the 3D FBP-based algorithm indeed provided a rather general formulation for image
      reconstruction from divergent projections (such as cone-beam and fan-beam
      projections). On the basis of this formulation we derived new approximate or
      exact algorithms for image reconstruction in circular cone-beam or fan-beam
      scans, which can be interpreted as special cases of the helical scan. Existing
      algorithms corresponding to the derived algorithms were identified. We also
      performed a preliminary numerical study to verify our theoretical results in each
      of the cases. The results in the work can readily be generalized to other non
      circular trajectories.

PMID- 15509071
TI  - Image reconstruction of anisotropic conductivity tensor distribution in MREIT:
      computer simulation study.
AB  - We describe a novel method of reconstructing images of an anisotropic
      conductivity tensor distribution inside an electrically conducting subject in
      magnetic resonance electrical impedance tomography (MREIT). MREIT is a recent
      medical imaging technique combining electrical impedance tomography (EIT) and
      magnetic resonance imaging (MRI) to produce conductivity images with improved
      spatial resolution and accuracy. In MREIT, we inject electrical current into the
      subject through surface electrodes and measure the z-component Bz of the induced
      magnetic flux density using an MRI scanner. Here, we assume that z is the
      direction of the main magnetic field of the MRI scanner. Considering the fact
      that most biological tissues are known to have anisotropic conductivity values,
      the primary goal of MREIT should be the imaging of an anisotropic conductivity
      tensor distribution. However, up to now, all MREIT techniques have assumed an
      isotropic conductivity distribution in the image reconstruction problem to
      simplify the underlying mathematical theory. In this paper, we firstly formulate
      a new image reconstruction method of an anisotropic conductivity tensor
      distribution. We use the relationship between multiple injection currents and the
      corresponding induced Bz data. Simulation results show that the algorithm can
      successfully reconstruct images of anisotropic conductivity tensor distributions.
      While the results show the feasibility of the method, they also suggest a more
      careful design of data collection methods and data processing techniques compared
      with isotropic conductivity imaging.

PMID- 15509072
TI  - Influence of the scalp thickness on the intracranial contribution to
      rheoencephalography.
AB  - In spite of the great efforts made by the scientific community, up to now there
      is no agreement about the rheoencephalography (REG) capability to reflect
      cerebral blood flow (CBF). Moreover, a standard procedure and the optimal
      electrode arrangement have not been established yet. In a previous study, we
      found, using a classical four-shell spherical model of the head and solving it by
      numerical methods that, theoretically, there could exist an electrode arrangement
      to register an REG II free of extracranial contribution. In this paper, we have
      studied the influence of scalp thickness on the intracranial contribution to REG
      II. The study has been performed by solving the head model, using in this case
      analytical methods, and then estimating the partial contribution of CBF
      pulsatility to REG for a given set of scalp thicknesses. Although our theoretical
      results validate the previous finding and suggest that, in some cases, an optimal
      electrode arrangement to register REG II exists, such an arrangement, and even
      its existence, is very sensitive to the subject's scalp thickness. According to
      this, there could not exist a universal electrode arrangement suitable for all
      individuals to register an REG II free of extracranial contribution, since it
      depends on the subject's physical constitution. This fact could explain the lack
      of agreement in the literature about REG interpretation.

PMID- 15509073
TI  - A method to measure the hyperelastic parameters of ex vivo breast tissue samples.
AB  - Over the past decade, there has been increasing interest in modelling soft tissue
      deformation. This topic has several biomedical applications ranging from medical
      imaging to robotic assisted telesurgery. In these applications, tissue
      deformation can be very large due to low tissue stiffness and lack of physical
      constraints. As a result, deformation modelling of such organs often requires a
      treatment, which reflects nonlinear behaviour. While computational techniques
      such as nonlinear finite element methods are well developed, the required
      intrinsic nonlinear mechanical parameters of soft tissues that are critical to
      develop reliable tissue deformation models are not well known. To address this
      issue, we developed a system to measure the hyperelastic parameters of small ex
      vivo tissue samples. This measurement technique consists of indenting an
      unconfined small block of tissue using a computer controlled loading system while
      measuring the resulting indentation force. The nonlinear tissue force
      displacement response is used to calculate the hyperelastic parameters via an
      appropriate inversion technique. This technique is based on a nonlinear least
      squares formulation that uses a nonlinear finite element model as the direct
      problem solver. The features of the system are demonstrated with two samples of
      breast tissue and typical hyperelastic results are presented.

PMID- 15509074
TI  - Nonlinear cardio-respiratory interactions revealed by time-phase bispectral
      analysis.
AB  - Bispectral analysis based on high order statistics, introduced recently as a
      technique for revealing time-phase relationships among interacting noisy
      oscillators, has been used to study the nature of the coupling between cardiac
      and respiratory activity. Univariate blood flow signals recorded simultaneously
      by laser-Doppler flowmetry on both legs and arms were analysed. Coupling between
      cardiac and respiratory activity was also checked by use of bivariate data and
      computation of the cross-bispectrum between the ECG and respiratory signals.
      Measurements were made on six healthy males aged 25-27 years. Recordings were
      taken during spontaneous breathing (20 min), and during paced respiration at
      frequencies both lower and higher than that of spontaneous respiration (either
      two or three recordings with a constant frequency in the interval between 0.09
      and 0.35 Hz). At each paced frequency recordings were taken for 12 min. It was
      confirmed that the dynamics of blood flow can usefully be considered in terms of
      coupled oscillators, and demonstrated that interactions between the cardiac and
      respiratory processes are weak and time-varying, and that they can be nonlinear.
      Nonlinear coupling was revealed to exist during both spontaneous and paced
      respiration. When present, it was detected in all four blood flow signals and in
      the cross-bispectrum between the ECG and respiratory signal. The episodes with
      nonlinear coupling were detected in 11 out of 22 recordings and lasted between 19
      s in the case of high frequency (0.34 Hz) and 106 s in the case of low frequency
      paced respiration (0.11 Hz).

PMID- 15509075
TI  - Electron beam quality correction factors for plane-parallel ionization chambers:
      Monte Carlo calculations using the PENELOPE system.
AB  - Simulations of three plane-parallel ionization chambers have been used to
      determine directly the chamber- and quality-dependent factors fc,Q, instead of
      the product (Sw,air p)Q, and kQ,Q0 (or kQ,Q,int) for a broad range of electron
      beam qualities (4-20 MeV) using divergent monoenergetic beams and phase-space
      data from two accelerators. An original calculation method has been used which
      circumvents the weakness of the so far assumed independence between stopping
      power ratios and perturbation factors. Very detailed descriptions of the geometry
      and materials of the chambers have been obtained from the manufacturers, and
      prepared as input to the PENELOPE 2003 Monte Carlo system using a computer code
      that includes correlated sampling and particle splitting. Values of the beam
      quality factors have been determined for the case of an electron reference beam.
      The calculated values have been compared with those in the IAEA TRS-398 dosimetry
      protocol and the differences analysed. The results for a NACP-02 chamber show
      remarkably good agreement with TRS-398 at high electron beam qualities but differ
      slightly at low energies. Arguments to explain the differences include
      questioning the undemonstrated assumption that the NACP is a 'perturbation-free'
      chamber even at very low electron beam energies. Results for Wellhofer PPC-40 and
      PPC-05 chambers cannot be compared with data from others for these chambers
      because no calculations or reliable experimental data exist. It has been found
      that the results for the PPC-40 are very close to those of a Roos chamber, but
      the values for the PPC-05 are considerably different from those of a Markus
      chamber, and rather approach those of a Roos chamber. Results for monoenergetic
      electrons and accelerator phase-space data have been compared to assess the need
      for detailed and costly simulations, finding very small differences. This
      questions the emphasis given in recent years to the use of 'realistic' source
      data for accurate electron beam dosimetry.

PMID- 15509076
TI  - Near surface photon energy spectra outside a 6 MV field edge.
AB  - The purpose of this study was to investigate the difference between a 6 MV linear
      accelerator x-ray energy spectrum outside the field edge near a phantom surface,
      and the corresponding spectrum on the central axis. The Monte Carlo code MCNP-4A
      was used to calculate the spectra on the central axis and at 1, 2, 5 and 10 cm
      from the edge of a 4 x 4 cm2, 10 x 10 cm2 and 15 x 15 cm2 field. Compared to the
      spectrum on the central axis, the spectra outside the field edge showed two
      distinct regions: a broad peak below about 0.5 MeV, and a lower amplitude, less
      rapidly changing region at higher energies from 0.5 to 6 MeV. The lower energy
      peak was due to scattered photons, and the higher energy component was due mainly
      to primary photons transmitted through the jaws of the secondary collimator. The
      potential impact of these spectral differences on critical organ photon dosimetry
      was determined by calculating the ratio of the sensitivity of a Scanditronix EDD
      5 diode and of a LiF:Mg:Ti thermoluminescent dosimeter (TLD) outside the field
      edge to their respective sensitivity at the calibration position on the central
      axis. The lower energy peak combined with the non-uniform energy sensitivity of
      each detector produced up to a two-thirds overestimate of x-ray dose outside the
      field by the diode, whereas the response ratio of the TLD was about unity. These
      results indicated that a similar evaluation was required for profile measurements
      of a dynamic wedged field and measurements in an intensity modulated beam with
      either type of detector.

PMID- 15509077
TI  - Spectral sensitivity study of dose distributions for a commercial
      convolution/superposition algorithm.
AB  - The focus of this study is to validate whether the sensitivity of dose
      distribution following the interface of different media can be used to
      distinguish between small variations of photon energy spectra in the context of
      the convolution/superposition algorithm in the polyenergetic implementation
      (Philips Pinnacle3, ADAC Laboratories, Milpitas, CA). Calculations were performed
      in homogeneous water and heterogeneous lung/water phantoms. Spectra were
      generated, in which the weights of the low-, medium- and high-energy components
      were adjusted sequentially. The heterogeneity correction factor CFlung, the
      D20/D10 ratio for homogeneous water and logarithmic derivative in buildup region
      LDbuildup were assessed for their relative ability to discriminate between
      different spectra for various field sizes. In accordance with another study
      (Charland et al 2004), the superior discrimination ability of the CFlung and
      LDbuildup tests over the D20/D10 test was observed for changes in an energy
      component as small as 0.3% of the total weight in the energy spectrum.
      Furthermore, new tests utilizing transverse dose profile data for discriminating
      between spectra, Fringe Index (FI) and Penumbra Index (PI), were introduced. The
      discrimination ability of the PI and FI tests was superior when a medium
      containing interface effects was exploited to obtain the transverse profile data
      (water/lung phantom for PIhung and FIlung tests) as opposed to when a homogeneous
      water medium was used (PIwater and FIwater tests).

PMID- 15509078
TI  - The use of gold nanoparticles to enhance radiotherapy in mice.
AB  - Mice bearing subcutaneous EMT-6 mammary carcinomas received a single intravenous
      injection of 1.9 nm diameter gold particles (up to 2.7 g Au/kg body weight),
      which elevated concentrations of gold to 7 mg Au/g in tumours. Tumour-to-normal
      tissue gold concentration ratios remained approximately 8:1 during several
      minutes of 250 kVp x-ray therapy. One-year survival was 86% versus 20% with x
      rays alone and 0% with gold alone. The increase in tumours safely ablated was
      dependent on the amount of gold injected. The gold nanoparticles were apparently
      non-toxic to mice and were largely cleared from the body through the kidneys.
      This novel use of small gold nanoparticles permitted achievement of the high
      metal content in tumours necessary for significant high-Z radioenhancement.

PMID- 15509079
TI  - The role of Triclosan in dentifrice formulations, with particular reference to a
      new 0.3% Triclosan calcium carbonate-based system.
AB  - AIM: To discuss the role of Triclosan in dentifrice systems and demonstrate the
      enhanced efficacy of Triclosan in calcium carbonate-based systems when the level
      of the antimicrobial agent is raised from 0.2% to 0.3%. Triclosan is the most
      commonly used antimicrobial agent in oral care products, being compatible with a
      wide range of ingredients found in toothpaste formulations, whilst having no
      negative sensory features (e.g. taste, staining) that are associated with some
      other antimicrobial/anti-plaque agents. Triclosan is a broad spectrum
      antimicrobial agent, with additional anti-metabolic and anti-inflammatory
      properties. When delivered to the mouth in oral care products, Triclosan can
      selectively inhibit Gram negative anaerobic bacteria implicated in gingivitis and
      periodontal diseases, while leaving species associated with oral health
      relatively unaffected. Worldwide, attempts have been made to boost
      delivery/activity of Triclosan, either by use of copolymers or by combination
      with other agents such as zinc citrate. However, Triclosan has also been shown to
      maintain clinical efficacy against plaque and gingivitis when present as the sole
      antimicrobial in toothpaste formulations.

PMID- 15509080
TI  - Antiplaque and antigingivitis efficacy of toothpastes containing Triclosan and
      fluoride.
AB  - OBJECTIVE: To compare the reduction of plaque and gingivitis from the following
      three toothpaste formulations containing: 0.3% Triclosan, 1,000ppm fluoride and
      0.13% calcium glycerophosphate in a natural calcium carbonate base (a new paste);
      0.2% Triclosan and 1,000ppm fluoride in a precipitated calcium carbonate base;
      0.3% Triclosan, 1,000ppm fluoride and Gantrez in a silica base. A control group
      was maintained, which used commercially available toothpastes without the above
      actives. METHODS: A double-blind, four-cell, stratified, parallel group design
      study. Subjects brushed twice daily with their allocated toothpaste for 12 weeks.
      Plaque, MGI and gingival bleeding assessments were carried out at baseline, after
      6 and 12 weeks of product use. RESULTS AND CONCLUSION: An analysis of covariance
      of the 12-week results showed significant differences between products [p<0.0001]
      for plaque, MGI and gingival bleeding. The new toothpaste formulation containing
      0.3% Triclosan, 1,000ppm fluoride and 0.13% calcium glycerophosphate in a natural
      calcium carbonate base was shown to be significantly more effective in reducing
      plaque and gingivitis than the other toothpaste formulations in the study.

PMID- 15509081
TI  - Low-levels of fluoride in plaque and saliva and their effects on the
      demineralisation and remineralisation of enamel; role of fluoride toothpastes.
AB  - AIM: To summarise support for current consensus on the likely means by which
      fluoride toothpastes reduce caries and review some relevant studies of the effect
      of low levels of fluoride on the demineralisation and remineralisation of enamel.
      The major anti-caries effect of fluoride toothpastes is thought to result from
      small but protracted elevations in levels of fluoride in plaque and saliva.
      Fluoride incorporated into enamel systemically does not reduce enamel solubility
      sufficiently to exert an anti-caries effect. Fluoride has the potential to exert
      an anti-caries benefit largely through three mechanisms; inhibition of
      demineralisation, promotion of remineralisation and interference with bacterial
      growth and metabolism. However, the low levels of fluoride thought to influence
      caries are insufficient to have a significant effect via the latter mechanism.
      Thus reductions in caries resulting from the use of fluoride toothpastes can be
      linked to modification of the demineralisation/remineralisation balance by direct
      effects on dental mineral exerted topically by low levels of fluoride. Numerous
      in vitro studies have shown that low levels of fluoride, typical of those found
      after many hours in resting plaque and saliva, and resulting from the regular use
      of fluoride toothpastes, can have a profound effect on enamel demineralisation
      and remineralisation.

PMID- 15509082
TI  - Calcium glycerophosphate and caries: a review of the literature.
AB  - AIM: To review studies in the dental literature regarding the anti-caries mode of
      action of glycerophosphate with special reference to calcium glycerophosphate.
      The cariostatic properties of calcium glycerophosphate have been demonstrated
      during numerous in vivo and in vitro studies. Several mechanisms have been
      suggested and these include plaque-pH buffering, elevation of plaque calcium and
      phosphate levels and direct interaction with dental mineral. There is credible
      evidence that calcium glycerophosphate has the potential to reduce the
      progression of caries via all of these mechanisms if it is applied frequently and
      at a sufficiently high concentration. Reduction of plaque mass has also been
      proposed as a cariostatic mechanism but this seems less likely. Animal studies
      have shown that the calcium glycerophosphate/sodium monofluorophosphate system
      can have a greater anti-caries effect than sodium monofluorophosphate alone and
      this was subsequently confirmed in a caries clinical trial. We conclude that
      elevation of calcium levels in plaque is the most likely explanation and that any
      means of enhancing this effect has significant promise as a means to further
      increase in anti-caries potential of the calcium glycerophosphate/sodium
      monofluorophosphate system compared to sodium monofluorophosphate alone.

PMID- 15509083
TI  - Sustained oral health improvement and use of toothbrushes and dentifrice by
      previous users of traditional materials in a rural population in Andhra Pradesh,
      India.
AB  - AIM: To follow-up, one year later, a double-blind, randomised study, which
      investigated the effect of regular brushing with dentifrices on the oral health
      of an economically disadvantaged rural population in Andhra Pradesh, India who
      were primarily users of traditional materials. SUBJECTS: 150 of the original
      study population. METHOD: Examination to determine whether the improvements in
      oral health status and oral health behaviour (use of toothbrush and dentifrice),
      being unsupported, had been sustained since completion of the original study.
      RESULTS: Data analysis showed sustained, statistically significant improvements
      in gingival health as measured by gingival bleeding and plaque indices (GBI and
      PI) comparing users and non-users of toothbrushes and dentifrice in the original
      study (PI: p = 0.04; GBI: p = 0.03) and sustained use of toothbrushes and
      dentifrice by 60% of the subjects at follow-up one year later. CONCLUSIONS: This
      study shows a beneficial effect on oral hygiene indices following the
      introduction of toothbrushes and dentifrices to a community using traditional
      oral hygiene materials and sustainability of use of these materials with
      motivation and support. It may therefore be concluded that it is feasible to
      achieve significant use of conventional toothbrushes and toothpastes, with
      consequent major and sustained improvements in plaque control and gingival health
      in a disadvantaged population hitherto often considered as not amenable to
      conventional oral hygiene for cultural or economic reasons.

PMID- 15509084
TI  - Effect of toothpaste with natural calcium carbonate/perlite on extrinsic tooth
      stain.
AB  - OBJECTIVE: The current study was designed to determine the effect of natural
      calcium carbonate toothpaste containing Perlite and microgranules (Whitening
      toothpaste) on extrinsic tooth stain compared to a standard commercial toothpaste
      formulation with precipitated calcium carbonate (PCC) as abrasive and a
      commercial toothpaste with dicalcium phosphate dihydrate (DCPD) as abrasive.
      METHODS: The toothpastes were evaluated in a double blind, three-cell, stratified
      (tobacco use; baseline tooth stain level), parallel group design study involving
      600 subjects with extrinsic tooth stain. Subjects brushed twice daily with their
      allocated toothpaste for four weeks. Extrinsic tooth stain was measured using the
      Macpherson modification of the Lobene stain index. RESULTS: ANCOVA showed
      significant differences between toothpastes (p=0.037). Subsequent multiple
      comparisons using pairwise t-tests, showed the Whitening toothpaste to be
      superior to the DCPD toothpaste (p=0.014) and the PCC toothpaste (p=0.067). When
      a Box-Cox transformation was made to the data (y0.6) to improve normality, these
      two differences were more accurately estimated at p=0.004 and p=0.03
      respectively. CONCLUSION: The Whitening toothpaste has been shown to be
      significantly more effective in tooth stain removal than the two standard
      commercial toothpaste formulations.

PMID- 15509085
TI  - [Significance of sex and gender studies for anthropology].
AB  - The formation of a special working group for gender studies within the German
      Anthropological Society (GfA) makes necessary a description of history as well as
      topics of gender studies within science and biological anthropology. In German
      speaking countries, gender studies are predominantly associated with social and
      cultural sciences, although very successful working groups belonging to natural
      sciences already exist. Unfortunately, up to now gender studies within natural
      sciences are often interpreted negatively and the existence of sex is denied.
      This may be due to the long and difficult history of gender studies in natural
      sciences. For a long time, pseudoscientific misinterpretations of results of
      gender studies were used to manifest the inferior social position of women.
      However, since more than thirty years respectable gender studies are integrated
      in social as well as natural sciences. Gender studies are integrative parts of
      nearly all subdisciplines of biological anthropology. The formation of a working
      group for gender studies within the GfA seems therefore to be useful.

PMID- 15509086
TI  - [The gender debate from the pedagogic perspective].
AB  - The question of form and extent of biological and/or cultural influences on
      female and male behaviour and performance is marking a major focus in present
      scientific research. Accordingly, a broad spectrum of approaches in research and
      interpretations of results is available. The recent debate on sex and gender is
      offering two basic objectives for research in education science: First, the
      critical review of the data and results on sex specifics presented in respect to
      the articulation of educational aims, topics and methods. Second, the intensified
      research focus on the developmental consequences of gender and gender roles for
      boys and girls, women and men. The pedagogical focus is discussed regarding the
      following three objectives: 1. developmental conditions in early ontogeny, 2. the
      question of sex specific differences in cognitive abilities in respect to school
      performance of adolescents, and 3. teaching knowledge on "sex" and "gender" in
      schools.

PMID- 15509087
TI  - [Cremation--biological source for gender research].
AB  - This article presents a project designed for prehistoric gender research. It
      focuses on the late Bronze Age to early Iron Age urnfield in Cottbus "Alvensleben
      Kaserne", Brandenburg. The cremation remains were emptied from the urns layer by
      layer. This provided excellent conditions for a critical reconstruction of the
      funeral rituals related to the cremation. Detailed recording of each bone
      fragment in each layer made possible the discovery of the ritual deposition of
      burnt bones according to the anatomical order. Cremated bones, a primarily
      biological source, are also a substantial resource for cultural historical
      research, e.g., on funeral practices as well as social structures.

PMID- 15509088
TI  - [Cribra orbitalia, dentin hypoplasia and life expectancy of 20-year-old persons
      as social and sex specific stress indicators in correlation with the health
      status of an early medieval population].
AB  - The aim of this study is based on the analysis of diachronically social and
      sexual specific considerations on the life situation of the early medieval
      population of Schleitheim, Kanton Schaffhausen, Switzerland. Cribra orbitalia and
      the linear enamel hypoplasia of the teeth are considered as stressors. This study
      is based on the life expectancy of the 20 years old, as the life expectancy gives
      information on the health condition of a social group or an entire population.
      The considered indicators show the same tendencies in three of the four social
      groups (women social group A and group B/C, men of the social group A). The
      female and male population of the social group A show a steady decrease in the
      indicator from the 5th century to come to its lowest level in the 7th century.
      The same parameters indicate a continuous increase in stress for the female
      population of the group B/C. Only one of the three indicators, the Cribra
      orbitalia, shows a positive tendency in the male population of the social group
      B/C from the 6th century to the following period, while hypoplasia and the life
      expectancy on the other hand indicate a negative tendency. The results show equal
      tendencies in the three independent indicators concerning three of the four
      social groups. This proves the high reliability of the indicators. These results
      are astonishing in two ways. First of all, the tendencies show that the
      originally better life situation of women of the higher ranking social group
      decreases in the following periods, whereas the women of the lower social group
      show an inverse development. This female population of low life situation in the
      5th century shows an increase in life qualities in the following periods.
      Remarkable, too, is the fact, that the female population of both social groups
      shows a lower level of stress than the corresponding male population. This fact
      is astonishing, as we would expect inverse results in a patriarchal society. This
      may point to a well known fact: Women show a higher vitality than the male
      population.

PMID- 15509089
TI  - Psychosocial and sociocultural aspects of infertility--a comparison between
      Austrian women and immigrant women.
AB  - The polycystic ovarian syndrome (PCOS) is the most common endocrine disorder
      affecting female fertility. In this study we examined psychosocial parameters
      caused by infertility in PCOS women with different socio-cultural background.
      Symptomatology of PCOS, body composition characteristics as well as psychosocial
      parameters were examined in 49 PCOS infertility patients of the University Clinic
      for Gynecology and Obstetrics in Vienna, who originated from two different socio
      cultural subgroups--Austrian women and Moslem immigrant women. In the appearance
      of the symptoms the typical heterogeneity of PCOS could be found in both
      subgroups with no differences. However, differences in the psychosocial aspects
      were impressive. Women from Islamic background do have a very high reproductive
      pressure. The Moslem immigrant PCOS women suffer more from infertility than
      Austrian women do.

PMID- 15509090
TI  - Testosterone levels and stress in women: the role of stress coping strategies,
      anxiety and sex role identification.
AB  - This study evaluated the relation between testosterone changes in response to
      anticipatory stress and several psychological variables that contribute to the
      stress reaction. Salivary testosterone was determined in 76 female students under
      stress-free conditions and before an important examination. Individual stress
      reactions were highly variable in direction and extent: both significant
      increases and decreases were found. Thus the data did not confirm previous
      findings of general increases in testosterone levels under stress in women.
      Depending on the women's level of trait anxiety (assessed via STAI) and the
      general use of positive or negative cognitive coping strategies (assessed via
      SVF), we found significant differences in their baseline testosterone levels.
      Individual endocrine changes under stress were correlated with baseline
      testosterone levels: High testosterone concentrations at rest were more likely to
      drop under anticipatory stress than low concentrations. These contrasting effects
      can be explained by the significant interaction of trait anxiety and the sex role
      dimension of masculinity (assessed via BSRI) with testosterone production in
      females.

PMID- 15509091
TI  - [Evolution of language: attempt at synthesis].
AB  - There are at least three traits that distinguish modern Homo sapiens from his
      closest relatives: bipedal locomotion, the unusual size of his brain and the
      ability to use symbolic language. To this day the emergence and evolution of
      these traits have not been explained sufficiently. New research in anthropology,
      linguistics, cognitive science and other disciplines shows, that the evolution of
      the human language faculty is a complex field that was influenced by a wide
      variety of factors. This paper tries to show the width of these factors and to
      work out the demands that are to be met by a theory of language evolution. After
      the introduction, in Section 2 the evolutionary principles and their role in the
      evolution of symbolic communication will be reviewed. Section 3 gives an overview
      of the results and controversies of brain evolution research, while Section 4
      introduces our current knowledge of the neuronal basis of language. In Section 5
      the controversies that had the greatest impact on the field and development of
      ways to solve them are reviewed before Section 6 summarizes the most important
      preadaptations for the evolving language faculty.

PMID- 15509092
TI  - [Secular trends of demographic parameters].
AB  - The aim of this paper is to describe the secular changes of selected demographic
      parameters and to investigate the possible causes for such changes as well as the
      biological relevance. We took into account the following parameters: population
      density, mean live expectancy, average age at marriage of until then unmarried
      persons, rate of live births, and number of children per woman. The results show
      that the population density (global and in Germany) especially in the twentieth
      century increased dramatically. We found a striking increase of life expectancy
      in Germany. Essential causes are rapid decreases in infant and maternal
      mortality. Since the 80s of the twentieth century the average age at marriage of
      until then unmarried persons as well as the number of single mothers show a
      permanent increase. Generally, the average age of mothers increased (for live and
      legitimate births). In the past 150 years we found a decrease in fertility rates
      in Germany. The registered demographic parameters show temporal and regional
      variations. These differences, especially between East Germany and West Germany,
      are emphasized.

PMID- 15509093
TI  - [Rectal tears in the horse: a literature review].
AB  - Rectal tears are a relatively rare complication of rectal palpation, mating, or
      dystocia, and idiopathic rectal perforation is an incidental finding. Rectal
      tears can be classified according to a 3 or a 4-grade system. This article
      describes medical and surgical treatment for rectal tears.

PMID- 15509094
TI  - [Rectal tears in the horse: two case reports].
AB  - Rectal tears occur incidentally and often have a poor prognosis. Early
      recognition of the problem and adequate therapy determine the outcome. The
      history, clinical examination, therapy, and outcome of two horses with grade IIIb
      and grade IV rectal tears are discussed.

PMID- 15509095
TI  - [Rectal tears in the horse: malpractice or an unfortunate accident?].
AB  - Rectal tears are a relatively rare complication of rectal palpation, mating or
      dystocia, and idiopathic spontaneous occurrence of rectal perforation has also
      been described. Rectal tears have been classified in a three or a four-grade
      system. Immediate recognition of the fact that a tear has been made and prompt
      action will improve the horses chance of survival, and is the best defence of the
      veterinarian against legislation. There is no clear explanation why rectal tears
      sometimes occur. A questionnaire of the Netherlands Equine Veterinary Association
      revealed that rectal tears occurred both to inexperienced veterinarians and to
      very experienced colleagues, working with or without a probe for ultrasonography.
      In the opinion of the authors, the approach in the legislation of rectal tears
      should be that a rectal tear is only considered 'malpractice' if the veterinarian
      obviously acted carelessly. However, this would create the ridiculous situation
      that it seems better for the veterinarian-client relationship when the
      veterinarian confesses to 'careless' rectal palpation. This point needs further
      clarification, and perhaps an 'insurance of the horse for rectal palpation' will
      be the solution. Further, retrospectively over the last ten years, the problem is
      often not 'making a rectal tear', but 'lacking recognition of making a tear'.
      Whenever a rectal tear is suspected, the veterinarian must assess its severity,
      discuss the problem openly with the owner and apply appropriate treatment
      including referral.

PMID- 15509096
TI  - [Death by cyathostominosis].
AB  - In autumn 2002 and 2003, the Animal Health Service received several young horses
      for post mortem investigation that had died or had been euthanised. It was found
      that severe cyathostominosis was the cause of death. The aetiology, pathology and
      diagnosis of this infection is discussed. Advice is given for preventative
      measures and usage of anthelmintics.

PMID- 15509097
TI  - [Night mare].

PMID- 15509098
TI  - [Hippo shoe and the Celtic horse shoe].

PMID- 15509099
TI  - [Transport of diagnostic samples].

PMID- 15509100
TI  - [Odontoclastic resorption lesions (ORL) and chronic gingivitis stomatitis in
      cats].

PMID- 15509101
TI  - [Study group meeting for cattle veterinarians during the National Cattle
      Manifestation].

PMID- 15509102
TI  - [The correct administration is fundamental to food safety. This also applies to
      the explanation of special emergency slaughter!].

PMID- 15509103
TI  - [The buyer and the clergyman].

PMID- 15509104
TI  - [Reaction to the article 'Severe adverse effects in collies'].

PMID- 15509105
TI  - [Confirmation organizational decision of private practice certification and
      recognition].

PMID- 15509106
TI  - Traumatology: the ultimate reward.

PMID- 15509107
TI  - A comparative study of mini-external fixation systems used to treat unstable
      metacarpal fractures.
AB  - We compared the biomechanical properties, clinical versatility, application ease,
      and financial cost of 7 mini-external fixation systems used to treat unstable
      metacarpal shaft fractures with segmental bone loss. Attached to a maple dowel
      fracture model, each fixator was tested in axial compression, lateral 4-point
      bending, 45 degrees apex-dorsal 4-point bending, and torsion. The EBI DynaFix
      system had the highest overall rigidity values and was highly versatile; the
      Synthes/AO Mini-External Fixator had intermediate rigidity values and was the
      lightest system tested; the Howmedica Mini-Hoffmann fixator was substantially
      less rigid than all the other tested constructs but was the most versatile.
      Devices constructed with polymethylmethacrylate and Kirschner wires were rigid,
      lightweight, and inexpensive. Routine use of these devices is discouraged,
      however, because of unacceptable loosening at the pin-cement interface during
      testing and because of difficulties encountered during construction and
      application. None of the external fixation systems tested was superior in all the
      parameters analyzed.

PMID- 15509108
TI  - Has locked plating completely replaced conventional plating?
AB  - The 2 main approaches to fracture plate fixation--compression plating and
      internal splinting--result in differing biomechanics and subsequent healing
      response patterns. A number of advantages to using the newer internal fixators
      have been described, but there are still several indications for traditional
      compression plating.

PMID- 15509109
TI  - External fixator pin tract infection model in the caprine (goat) tibia: a
      randomized, prospective, blinded study.
AB  - Six goats had 2 Schanz pins inserted in each tibia. Twenty-four pins were
      inoculated with saline or Staphylococcus aureus. Three investigators, blinded to
      the inoculum, evaluated 23 pins at 14 days. Clinical pin tract infections
      developed in all inoculated pins and in 5/12 uninoculated pins, Quantitative
      cultures demonstrated that infections were produced in 10/11 inoculated and in
      0/12 uninoculated pins. Prediction of culture status by clinical criterion
      (P<.01, Fisher Exact Test) had 100% sensitivity and a 58% specificity. The
      prediction of infection in inoculated sites by culture criterion (P<.001, Fisher
      Exact Test) had a 91% sensitivity and 100% specificity. A reproducible long bone
      pin tract infection model was developed that produced clinically and
      microbiologically evident pin tract infections.

PMID- 15509110
TI  - Tape blisters that develop after hip fracture surgery: a retrospective series and
      a review of the literature.
AB  - A tape blister, a skin excoriation that occurs under the taped portion of
      surgical bandages, can be a source of postoperative morbidity. Tape blisters are
      caused by the separation of the epidermis from the dermis at the dermal-epidermal
      junction. Tape resistant to stretching contributes to blister formation because
      of the concentration of forces at the ends of the tape. Although tape blisters
      are a pervasive clinical problem, their incidence after hip surgery has rarely
      been reported in the orthopedic literature. Therefore, we retrospectively
      reviewed a consecutive series of patients with hip fractures to determine the
      incidence of tape blisters at our institution. One hundred three patients were
      included in the study. Tape-related injuries occurred in 22 patients (21.4%).
      Patient age, patient sex, number of medical comorbidities, smoking history,
      nutritional status, and type of surgery were not statistically significantly
      associated with risk for developing tape blisters.

PMID- 15509112
TI  - Ilizarov external fixation salvage of failed intramedullary fixation of tibia
      with nail retention.
AB  - Failure of intramedullary fixation of the tibia presents a unique problem, as
      improving fracture alignment is often difficult after nail placement. The purpose
      of this study was to demonstrate the effectiveness of the Ilizarov technique in
      obtaining anatomic union after failed intramedullary fixation of the tibia. We
      reviewed medical records and plain radiographs of 4 men who, at a tertiary-care
      facility, presented with failed intramedullary fixation of the tibia. Mean age
      was 28 years (range, 23-36 years). All 4 patients underwent reduction and
      external fixation by the llizarov technique with retention of the intramedullary
      nail. Anatomic union was attained in each case. Thin-wire circular-frame external
      fixation by the Ilizarov technique was a viable salvage option for failed
      intramedullary fixation of the tibia.

PMID- 15509111
TI  - Bilateral femoral neck fractures after pelvic irradiation.
AB  - Our patient, who had no history of trauma, developed bilateral femoral neck
      fractures several years after pelvic irradiation. The well-documented sequelae of
      femoral neck fractures include avascular necrosis, nonunion, and malunion.
      Postirradiation pelvic pain, particularly in the absence of trauma, should be
      aggressively evaluated. With high clinical suspicion and normal plain
      radiographs, MRI can be used to exclude potentially serious fractures.

PMID- 15509113
TI  - Floating knee injuries treated with single-incision technique versus traditional
      antegrade femur fixation: a comparative study.
AB  - Forty-three patients with floating knee injuries were treated from January 1994
      through March 1999. The study group consisted of 25 patients treated with
      retrograde nailing of the femur and antegrade nailing of the tibia through a
      single incision, and the control group consisted of 18 patients treated with
      traditional femoral and tibial antegrade intramedullary nailing. The femoral
      retrograde technique required less set-up time, anesthesia time, and surgical
      time than did the traditional femoral antegrade technique and was associated with
      less estimated blood loss. We conclude that the single-incision technique is a
      safe and faster alternative procedure for type I floating knee injuries.

PMID- 15509114
TI  - Percutaneous antegrade intramedullary nailing of the femur in obese patients.
AB  - Antegrade intramedullary nailing using the piriformis fossa as an entry point for
      insertion has become the treatment of choice for most diaphyseal fractures of the
      femur. In obese or well-muscled patients, however, creating an entry point can be
      difficult. This difficulty has led some authors to switch to retrograde
      intramedullary nailing. Unfortunately, retrograde nailing is associated with
      higher nonunion rates and increased incidence of knee pain and stiffness. We
      describe an antegrade nailing technique that is useful and easy to perform even
      in obese patients.

PMID- 15509115
TI  - Counterfeit drugs lawsuit points finger at wholesaler, pharmacy.

PMID- 15509116
TI  - Details matter in bedside bar-code scanning.

PMID- 15509117
TI  - Six Sigma black-belt pharmacist improves patient safety.

PMID- 15509118
TI  - Medicare law motivates hospitals to report quality data. Changes to inpatient
      prospective payment system start October 1.

PMID- 15509119
TI  - Oral ascorbic acid as adjuvant to epoetin alfa in hemodialysis patients with
      hyperferritinemia.

PMID- 15509120
TI  - Approved use of gefitinib.

PMID- 15509121
TI  - Measuring the impact of drug shortages.

PMID- 15509123
TI  - Emergency contraception: the right to full disclosure.

PMID- 15509124
TI  - National survey of the impact of drug shortages in acute care hospitals.
AB  - PURPOSE: The impact of drug shortages on patient care, the resources used to
      manage drug shortages, and the cost associated with drug shortages were studied.
      METHODS: A national online survey was conducted to quantify the effects of drug
      shortages on patient care and pharmacy expenses. Directors of pharmacy in acute
      care institutions in the ASHP member database were asked to estimate the impact
      of drug shortages on acquisition costs, pharmacist and nonpharmacist staff time
      dedicated to specific functions related to drug shortages, and drug-compounding
      expenses. RESULTS: Usable responses were received from 370 (24.7%) of 1496
      pharmacy directors. Nearly all pharmacy directors surveyed believed that
      shortages had changed practice, and a majority felt that drug shortages had
      compromised patient care. Hospital pharmacy personnel devoted a significant
      amount of time to managing drug shortages. The results suggest that shortages
      increase the acquisition cost of pharmaceuticals in the United States by over
      dollar 99 million annually. CONCLUSION: A national survey indicated that drug
      shortages are having a significant impact on patient care activities and finances
      in hospitals.

PMID- 15509125
TI  - Current status of pharmacist-operated drug information centers in the United
      States.
AB  - PURPOSE: Pharmacist-operated drug information centers (DICs) in the United States
      and Puerto Rico were surveyed, and the results were compared with those of
      similar surveys conducted over the past 30 years. METHODS: In January 2003,
      surveys were mailed to 151 institutions that were thought to have an organized
      DIC, defined as a center that regularly accepts a broad scope of requests from
      health care professionals, regardless of the location or affiliation of those
      professionals. The survey covered such topics as affiliations, staffing,
      services, resources, quality assurance, involvement in education, and funding.
      RESULTS: One hundred nineteen DICs responded (79%), of which 81 met the criteria.
      Hospitals and medical centers and colleges and schools of pharmacy continued to
      be the most commonly reported affiliations. The number of DICs declined in the
      past decade, and the number of DIC pharmacists and other personnel was the lowest
      reported in the past 30 years. Drug information pharmacists appeared to be better
      trained than in the past, and a larger percentage had advanced degrees. Services
      provided by DICs remained consistent with previous findings, except for greater
      participation in the training and education of pharmacy students and residents.
      The resource most commonly reported by DICs as useful was Micromedex Healthcare
      Series, followed by MEDLINE and AHFS Drug Information. The percentage of DICs
      with formal quality assurance programs did not change significantly in the past
      decade. Funding sources and fee-for-service activities remained the same.
      CONCLUSION: The number of DICs has declined steadily since 1986, and the number
      of drug information pharmacists is at its lowest in 30 years. DIC services
      continue to be comprehensive. Only half of the DICs surveyed had a formal quality
      assurance program.

PMID- 15509126
TI  - Directory of pharmacist-operated drug information centers in the United States-
      2003.

PMID- 15509127
TI  - Association of medication adherence, knowledge, and skills with emergency
      department visits by adults 50 years or older with congestive heart failure.
AB  - PURPOSE: The association of medication adherence, knowledge, and skills with
      emergency department (ED) visits by patients 50 years of age or older with
      congestive heart failure (CHF) was studied. METHODS: The patients in this study
      were enrolled in the usual care group of an ongoing trial of patients with CHF to
      determine the effects of a pharmacy-based intervention on relevant outcomes.
      Participants' medication knowledge and skills were assessed during individual
      interviews. Medication knowledge assessed patients' knowledge of the dosage,
      frequency, and indication of each of their CHF medications. The medications
      skills assessment evaluated patients' dexterity (ability to open medication
      bottles), literacy (ability to read labels), and ability to distinguish colors of
      tablets and capsules. Medication adherence to CHF drugs was calculated from
      electronic monitors and prescription-refill records over a six-month period. The
      primary outcomes of this study were the numbers of all-cause cardiovascular and
      CHF-specific ED visits during a six-month period. Log-linear regression models
      were used to analyze the effects of medication knowledge, skill, and adherence on
      ED visits. RESULTS: Sixty-one patients participated in this study. Multivariate
      log-linear models adjusted for demographic variables showed that lower medication
      adherence (p < 0.001) and an inability to read standard prescription and
      auxiliary labels (p = 0.002) were associated with an increased number of
      cardiovascular-related ED visits. Knowledge of the prescribed dose was associated
      with CHF-specific ED visits (p < 0.001). CONCLUSION: Greater medication
      knowledge, skills, and adherence were associated with fewer ED visits among
      patients 50 years of age or older with CHF in an urban, teaching medical center.

PMID- 15509128
TI  - Metabolic complications of parenteral nutrition in adults, Part 2.
AB  - PURPOSE: Common metabolic complications associated with parenteral nutrition (PN)
      are reviewed, and the consequences of overfeeding and variables for patient
      monitoring are discussed. SUMMARY: Although PN is a lifesaving therapy in
      patients with gastrontestinal failure, its use may be associated with metabolic,
      infectious, and technical complications. The metabolic complications associated
      with PN in adult patients include hyperglycemia, hypoglycemia, hyperlipidemia,
      hypercapnia, refeeding syndrome, acid-base disturbances, liver complications,
      manganese toxicity, and metabolic bone disease. These complications may occur in
      the acute care or chronic care patient. The frequency and severity of these
      complications depend on patient- and PN-specific factors. Proper assessment of
      the patient's nutritional status; tailoring the macronutrient, micronutrient,
      fluid, and electrolyte requirements on the basis of the patient's underlying
      diseases, clinical status, and drug therapy and monitoring the patient's
      tolerance of and response to nutritional support are essential in avoiding these
      complications. Early recognition of the signs and symptoms of complications and
      knowledge of the available pharmacologic and nonpharmacologic therapies are
      essential to proper management. PN should be used for the shortest period
      possible, and oral or enteral feeding should be initiated as soon as is
      clinically feasible. The gastrointestinal route remains the most physiologically
      appropriate and cost-effective way of providing nutritional support. CONCLUSION:
      PN can lead to serious complications, many of which are associated with
      overfeeding. Close management is necessary to recognize and manage these
      complications.

PMID- 15509129
TI  - Continuing professional development in pharmacy.

PMID- 15509130
TI  - Hormone replacement therapy--practical recommendations.

PMID- 15509131
TI  - Effects of valsartan/hydrochlorothiazide and amlodipine on ambulatory blood
      pressure and plasma norepinephrine levels in high-risk hypertensive patients.
AB  - The efficacy and tolerability of the combination of valsartan and
      hydrochlorothiazide (HCTZ) were compared with that of amlodipine in reducing
      ambulatory blood pressure and plasma norepinephrine levels in patients with mild
      to moderate hypertension and at least 1 cardiovascular risk factor. At the end of
      a 2-week washout period, 92 outpatients with a sitting diastolic blood pressure >
      or =95 and <110 mm Hg, associated with at least 1 additional risk factor, were
      randomly assigned to receive either valsartan 160 mg and HCTZ 12.5 mg once daily
      (n=46) or amlodipine 10 mg alone once daily (n=46) for 12 weeks, according to a
      prospective, randomized, open-label, blinded end point, parallel-group design. At
      the end of the washout period and after 6 and 12 weeks of active treatment, 24
      hour ambulatory blood pressure monitoring was performed, and clinical blood
      pressure and heart rate and plasma norepinephrine levels were assessed (by high
      performance liquid chromatography). Both the valsartan/HCTZ combination and
      amlodipine had a demonstrable antihypertensive effect, but the combination showed
      an antihypertensive effect significantly greater than that of amlodipine, as
      demonstrated by the 24-hour (P<.001), daytime (P<.001), and nighttime ambulatory
      blood pressure values (P<.01) and by the clinical blood pressure values at
      trough, which were all significantly lower. Although the trough-to-peak ratios
      were similar in both groups, the smoothness indexes pertaining to both systolic
      and diastolic pressures were significantly higher (P<.05 and P<.001,
      respectively) in patients receiving valsartan/HCTZ, suggesting the combination
      produces a more homogeneous anti-hypertensive effect. A significant increase in
      plasma norepinephrine levels was associated with amlodipine (+9% at 6 weeks, +15%
      at 12 weeks) but not with the valsartan/HCTZ combination. The valsartan/HCTZ
      combination was better tolerated than amlodipine, which was associated with a
      higher frequency of ankle edema. These results indicate that the combination of
      valsartan 160 mg and HCTZ 12.5 mg provides more sustained and homogeneous control
      of blood pressure than does amlodipine 10 mg in high-risk hypertensive patients,
      without producing reflex sympathetic activation.

PMID- 15509132
TI  - Psychometric validation of a patient-reported sensory perception and preference
      instrument: the Sensory Perceptions Questionnaire.
AB  - This study evaluated the psychometric properties of content validity, construct
      validity, and test-retest reliability of a 23-item Sensory Perceptions
      Questionnaire (SPQ) used to survey sensory perceptions of intranasal
      corticosteroid sprays. Two patient cohorts (men and women aged > or =18 years who
      had at least a 1-year history of allergic rhinitis and had been using a
      corticosteroid nasal spray) were enrolled. The content validity and construct
      validity of the SPQ questions were evaluated using a cognitive debriefing method
      after cohort 1 (n=15) completed the SPQ. Test-retest reliability (assessed with
      intraclass correlation coefficients [ICCs] of the SPQ questions) was evaluated in
      cohort 2 (n=50), after they answered a Web-based version of the SPQ on two
      occasions, each separated by 7 days. In cohort 1, 7 of 15 patients believed all
      relevant sensory perceptions were addressed in the questionnaire. Although 8
      patients mentioned at least 1 sensory perception that was not addressed, only 4
      sensory perceptions were mentioned by more than 1 patient, and none was mentioned
      reliably by more than 2 patients. Those 4 sensory perceptions not addressed in
      the SPQ were all intentionally excluded, because they were potential symptoms of
      rhinitis or adverse events associated with intranasal corticosteroid spray use.
      Patients regarded the questions as straightforward, nonburdensome, and
      nonthreatening, signs suggesting the questions were not likely to challenge the
      construct validity of the SPQ. The responses to 2 questions (one in which
      patients were asked to indicate whether they were pleased or displeased overall
      with a particular spray; the other to indicate their overall product preference)
      were somewhat influenced by the effectiveness of the sprays. Results of test
      retest reliability (cohort 2) showed both high (>0.8) and low (<0.7) ICCs. A high
      degree of correspondence between the 2 administrations produced a low between
      patient variance, which likely resulted in lower ICCs. The SPQ adequately
      represents the sensory attributes reported by patients regarding intranasal
      corticosteroid spray use and, overall, is a valid measure of patient preference
      based on sensory perception.

PMID- 15509133
TI  - Thyroid storm induced by aspirin intoxication and the effect of hemodialysis: a
      case report.
AB  - Thyroid dysfunction is one of the serious consequences of an overdose of
      acetaminophen, aspirin, or nonsteroidal antiinflammatory drugs. The management of
      such consequences remains a medical challenge. A variety of thyroid abnormalities
      are common in clinical practice and can, in many cases, be accurately diagnosed
      and managed by the primary care physician. This case study covers an aspirin
      overdose causing thyroid storm that was treated successfully with hemodialysis.

PMID- 15509134
TI  - In vitro and ex vivo antioxidant activities of labetalol on rabbit neutrophil
      respiratory burst.
AB  - The beta-adrenoreceptor blocker labetalol has demonstrated important antioxidant
      properties in vitro that inhibit superoxide anion production during normal
      leukocyte oxidative metabolism. This study investigated the in vitro and ex vivo
      effects of labetalol on respiratory burst in rabbit neutrophils. The production
      of superoxide anions was examined in activated purified rabbit neutrophils after
      intravenous administration of labetalol (4.0 mg/kg of body weight). At a
      concentration up to 200 mg/L, labetalol did not demonstrate any cytotoxic effects
      on neutrophils, as determined by enzyme lactate dehydrogenase activity. In the
      cell-free system, labetalol demonstrated no significant activity, but in formyl
      methionyl-leucyl-phenylalanine (fMLP)-stimulated rabbit neutrophils, labetalol
      demonstrated concentration-dependent antioxidant activity. The in vitro 50%
      inhibitory concentration (IC50) with the fMLP stimulus was 16.5+/-0.21 mg/L in
      the rabbit neutrophils and 13.2+/-0.16 mg/L in the human neutrophils. In the fMLP
      stimulated rabbit polymorphonuclear leukocytes, labetalol demonstrated its peak
      inhibitory activity (47%) 3 hours after administration. The mechanism by which
      labetalol acts in the treatment of hypertension may occur from an interaction in
      the signaling pathway of protein kinase C activation. The antioxidant properties
      demonstrated in this mechanism contribute to the drug's antihypertensive action
      and thus, may reduce the risk of injuries inflicted by reactive oxygen species
      involved in the pathogenesis of hypertension.

PMID- 15509136
TI  - Efficacy and tolerability of a combination of Lyprinol and high concentrations of
      EPA and DHA in inflammatory rheumatoid disorders.
AB  - This 12-week drug-monitoring study was conducted to evaluate the efficacy of
      Sanhelios Mussel Lyprinol Lipid Complex on 50 adult men and women with
      inflammatory rheumatoid arthritis. A total of 34 patients required drug therapy
      before and during the study. By the end of the study, 21 (62%) patients were able
      to reduce their dosage and 13 were able to terminate drug therapy. At the end of
      the treatment period, 38% were regarded symptom free, and the number of patients
      with severe pain decreased significantly from 60% at baseline to 25% at the
      completion of the trial. A significant effect was observed for each investigated
      parameter. The special combination of Lyprinol and omega-3 fatty acids was
      generally very well tolerated, with only one, nonserious adverse event (mild
      nausea) reported. This dietary supplement may therefore be considered an
      effective and well-tolerated component of treatment regimens for inflammatory
      rheumatoid arthritis.

PMID- 15509135
TI  - Effects of cyclosporine and tacrolimus on maintenance therapy after renal
      transplantation.
AB  - The immunosuppressive agents cyclosporine A and tacrolimus have demonstrated
      efficacy in preventing acute organ rejection after renal transplantation, but no
      comparative studies of these 2 agents have been published. This study compared
      the effects of tacrolimus and cyclosporine A on the renal function, blood
      pressure, and serum glucose and lipid levels of patients who underwent
      cyclosporine A therapy and C2 monitoring or tacrolimus therapy and standard
      monitoring during the first 24 months after transplantation. By the end of the
      follow-up period, no significant difference between either treatment group was
      noted in the measures of creatine clearance; BUN, glucose, uric acid, and lipid
      levels; or diastolic blood pressure (P>.05 for all), which were maintained at
      normal values throughout the study. Systolic blood pressure was significantly
      lower in the cyclosporine A group at the end of the 1 st month (P<.025) but this
      difference was not evident at months 6, 12, and 24 (P>.05). These results
      indicate that tacrolimus and cyclosporine (when combined with C2 monitoring) were
      equally effective and safe in preventing acute organ rejection.

PMID- 15509137
TI  - Crisis--a wide range of issues.

PMID- 15509138
TI  - Assessment and aftercare for deliberate self-harm patients provided by a general
      hospital psychiatric service.
AB  - We report on a sample of 135 deliberate self-harm (DSH) patients who were
      assessed by a general hospital DSH service, and on those who were offered
      aftercare by, or telephone open access to, the service. Patients' satisfaction
      with assessment and treatment, and their outcome were investigated at follow-up
      12-20 months later. Four-fifths of patients reported the assessment following DSH
      to have been helpful and the assessor sympathetic. Thirty-three (24%) of the 135
      patients assessed were offered treatment by the DSH service but 13 declined or
      failed to attend. Of the 20 who engaged in treatment, 17 (94%) were satisfied
      with their care. Open access to the DSH service by telephone was offered to 53
      (39%) patients, nine (22%) of whom reported at follow-up that they had used this
      facility. A specialist DSH service can effectively assess and treat patients
      following DSH. It is important that the service is accessible and acceptable to
      patients.

PMID- 15509139
TI  - The main factors of repetition: review of some results of the Pecs Center in the
      WHO/EURO Multicentre Study on Suicidal Behaviour.
AB  - The authors obtained more information about the characteristics of suicide
      attempters in order to examine the most important differences between those who
      attempted suicide for the first time (first-evers) and those who had a previous
      attempt (repeaters). Within the framework of the WHO/EURO Multicentre Study on
      Suicidal Behaviour in Pecs Center, 1158 cases of parasuicide were collected over
      4 years (July 1, 1997-June 30, 2001). In the monitoring sample, 728 (62.9%)
      parasuicide acts were committed by women and 430 (37.1%) by men, and more than
      half of the attempters had made a previous attempt In the logistic regression
      model a higher risk of repetition was found to be related to being divorced (OR
      1.84), unemployed or economically inactive (OR 1.45), and without higher
      education (OR 2.54). In the sample, mental disorders were the most significant
      risk factor for repeated attempts. The odds ratio was highest (OR 5) for
      personality disorders. The results may reflect (besides some factors of social
      destabilization) a higher importance of major mental health problems among
      repeaters. For this reason, more effective recognition and treatment of the
      underlying psychiatric and social conditions of suicide attempters has special
      importance to prevent future suicidal behaviour.

PMID- 15509140
TI  - Suicide outside of prison settings among males under investigation for sex
      offenses in Ireland during 1990 to 1999.
AB  - Thirty-two cases of suicide outside prison were identified among 7008 Irish men
      under investigation for sexual offenses between 1990 and 1999. Previously this
      risk category has not been identified. Risk ratios of 1/1644 for those accused of
      offenses against adults, and 1/24 for those accused of offending against minors,
      respectively, were estimated based on the conservative estimates found here. The
      increase in the base rate of suicide in Ireland during the study period is an
      insufficient explanation. The frequency is comparable to prison suicides for the
      period, and the population of risk may overlap. The incidence increases over the
      study period. It outpaces increases in prosecutions and may reflect responses to
      the changing social environment of these investigations. These men use community
      psychiatric services that may need to become aware of the increased risk of
      suicide they pose.

PMID- 15509141
TI  - Risk of suicide ideation associated with problem-solving ability and attitudes
      toward suicidal behavior in university students.
AB  - The present paper investigates the risk of lifetime suicide ideation associated
      with problem-solving ability and attitudes toward suicidal behavior in a sample
      of 328 university students (41% male, 59% female). The response rate was 77%
      based on the total number of students registered for the relevant courses. A
      series of questions assessed lifetime suicide ideation, while problem solving and
      attitudes toward suicide were measured using the Self-Rating Problem Solving
      scale and four subscales of the Suicide Opinion Questionnaire, respectively
      (McLeavey, 1986; Domino et al., 1989). Almost one-third of the students surveyed
      had lifetime suicide ideation. Both genders were similar in terms of their
      suicide ideation history, problem solving, and attitudes toward suicidal behavior
      with the exception that male students were more in agreement with the attitude
      that suicidal behavior lacks real intent. Compared with 2% of nonideators and
      ideators, one in four planners reported that they would more than likely attempt
      suicide at some point in their life. Greater agreement with the attitude that
      suicidal behavior is normal was associated with significantly increased risk of
      being an ideator, as was poor problem solving and less agreement with the
      attitude that suicidal behavior is associated with mental illness.

PMID- 15509142
TI  - Suicidal behavior in patients diagnosed with cancer of the cervix.
AB  - There is a paucity of literature on suicide and cancer, especially cancer of the
      cervix. This study reports on suicidal behavior in these patients. The sample
      consisted of adult, black, Zulu-speaking women from palliative and radical
      oncology treatment groups who volunteered for the study. There were more patients
      in the palliative group who were younger, and had a more significant delay
      between cancer symptom presentation and seeking oncology treatment. Patients
      experienced: significant depression, anxiety, stress, hopelessness/helplessness,
      anxious preoccupation about their disease, poor current or delayed social
      support, feelings of being a burden to their significant others, beliefs that
      they would be better off dead, perceptions that they were stigmatized by society
      or that their communities suspected them of being HIV-AIDS positive, and
      suppressed anger. More patients in the palliative, compared to the radical
      treatment, group were inclined toward suicidal ideation with serious intent.
      Overall, most patients coped inadequately with their disease and its management.
      These patients are a high risk group for suicidal behavior and should be
      identified in time for appropriate psychological intervention.

PMID- 15509143
TI  - The variation of the mean age of suicides in the United States.
AB  - In the United States from 1968-1996, the mean age of suicides was positively
      associated with measures of domestic social integration. It is suggested that the
      mean age of suicides could be an interesting dependent variable in suicidological
      research.

PMID- 15509144
TI  - Can a louse commit suicide? Letter across the pacific.

PMID- 15509145
TI  - Hanging crepe in suicide prevention.

PMID- 15509146
TI  - Depression and suicidal behavior.

PMID- 15509147
TI  - Preventing suicide in schizophrenia inside the family environment.

PMID- 15509148
TI  - Cancer incidence and mortality in Asian Indians: a review of literature from the
      United States, South Asia, and beyond.
AB  - OBJECTIVE: The purpose of this paper is to provide a framework for future
      research and awareness activities in the United States. METHODS: The current
      literature in the English language on cancer incidence and mortality among Asian
      Indians was reviewed. RESULTS: Asian Indians comprise 89% of the U.S. South Asian
      population. There are few studies in the United States or Canada on cancer
      incidence or mortality. In India, oral and cervical cancers have high incidence
      and mortality rates, but the rates of cancers common in the West are rising. In
      Great Britain, cancer rates in the South Asian community are similar to those of
      their non-Asian counterparts. CONCLUSIONS: Cancer incidence and mortality rates
      in India and Great Britain provide a foundation for scientific inquiry among this
      population in the United States, but more data is needed to assess the cancer
      burden and implement cancer prevention activities in this country.

PMID- 15509149
TI  - Cancer in Asian American males: epidemiology, causes, prevention, and early
      detection.
AB  - OBJECTIVES: The objective of this paper is to discuss the epidemiology, etiology,
      and cultural phenomena that characterize cancers specific to Asian American
      males. METHODS: The author reviewed various published literature concerning the
      health of Asian American males. RESULTS: Data show an epidemiological dichotomy
      in cancer incidences between Asian American males and the general U.S. male
      population. First, lung and colorectal cancers are among the top three cancers
      for most Asian groups, similar to the situation in the White population. Second,
      prostate cancer is the leading, or second leading, cause of cancer for Chinese,
      Japanese, and Filipino males -- all groups considered, in U.S. terms, to be more
      established in their migration patterns. Third, liver and stomach cancer are in
      the top five cancers for most Asian groups, an incidence not shared by the White
      population. CONCLUSIONS: The most common cancers in Asian American males involve
      the interplay of host genetic and environmental factors, and both primary and
      secondary prevention strategies are necessary to decrease the morbidity and
      mortality rates of this uniquely diverse population.

PMID- 15509150
TI  - Cervical cancer among young Vietnamese American women: incidence, risk factors,
      and early detection.
AB  - OBJECTIVES: This paper has three objectives: 1) to review the problem of cervical
      cancer in Vietnamese American women; 2) to identify the gaps in the published
      literature regarding this problem in young Vietnamese American women; and 3) to
      gain a better understanding of their health behavior in order to address an
      important health concern for this population in the future. METHODS: Published
      literature about the health status of Vietnamese American women was reviewed.
      RESULTS: Little has been published about the health of Young Vietnamese American
      women (are 18-30), the age group at highest risk for Hepatitis B infection. Also,
      it is unclear why they do not have regular Pap screenings. CONCLUSIONS: A greater
      understanding of this population's high-risk behaviors, such as sexual and
      smoking behaviors, must be reached. More research is needed on the impact of
      acculturation and their knowledge and understanding of screening. Educational
      approaches targeting risky behaviors and the need for screening must be
      developed. Implementation of effective health education and disease prevention
      strategies are needed.

PMID- 15509151
TI  - The absence of cancer prevention for the Thai population in the U.S.
AB  - OBJECTIVES: In this paper, we assess the state of scientific study of cancer
      among Thais, one of the most underserved AAPI populations. METHODS: We reviewed
      published literature and a database of Federally-funded research in the United
      States. RESULTS: We found virtually no cancer-related research on the Thai
      population in the U.S. A review of the international literature, including
      studies conducted in Thailand, shows that Thais are at significant risk for
      developing lung, liver, colorectal, breast, and cervical cancers. CONCLUSIONS:
      Given the sizable Thai population in the U.S. and the high likelihood that this
      population has been suffering from cancer, we recommend that Thais be classified
      separately in cancer registries and that they receive culturally meaningful
      outreach and support.

PMID- 15509152
TI  - The health status of Vietnamese immigrants in Hawaii from chart records.
AB  - OBJECTIVES: We determined the most common diseases among adult Vietnamese men and
      women in Hawaii. METHODS: A chart review of 952 adult Vietnamese patients was
      conducted between January and February 2000. A data collection form with 39
      categories of diagnosed chronic illnesses or problems was used. The study was
      conducted at a Vietnamese internist's private medical office in Honolulu, HI.
      RESULTS: Chart review revealed that the five most prevalent diagnostic conditions
      seen in Vietnamese men, from the highest to lowest frequency, were
      gastrointestinal disorders (39%), cutaneous conditions (31%), lower back pain
      (23%), headache (18%), and allergies (18%). In women, gastrointestinal disorders
      (38%), cutaneous conditions (34%), headache (32%), gynecologic conditions (30%),
      and arthritic diseases (24%) were most common. Gender, years of U.S. arrival, and
      types of occupation were significantly correlated with certain diseases (p< or
      =0.05). CONCLUSIONS: This is the first study to examine frequency of diseases
      diagnosed in an ambulatory care setting in a cohort of Vietnamese patients in
      Hawaii.

PMID- 15509153
TI  - Involving cancer survivors in cancer awareness and support: lessons learned from
      10 years of experience with Chinese women in San Francisco.

PMID- 15509154
TI  - Identification of a selective inverse agonist for the orphan nuclear receptor
      estrogen-related receptor alpha.
AB  - The estrogen-related receptor alpha (ERRalpha) is an orphan receptor belonging to
      the nuclear receptor superfamily. The physiological role of ERRalpha has yet to
      be established primarily because of lack of a natural ligand. Herein, we describe
      the discovery of the first potent and selective inverse agonist of ERRalpha.
      Through in vitro and in vivo studies, these ligands will elucidate the endocrine
      signaling pathways mediated by ERRalpha including association with human disease
      states.

PMID- 15509155
TI  - NO-sartans: a new class of pharmacodynamic hybrids as cardiovascular drugs.
AB  - The aim of this work was to develop lead pharmacodynamic hybrids, NO-sartans,
      possessing the characteristics of a typical AT1-antagonist and of a "slow NO
      donor", by adding NO-donor side chains to losartan. These new compounds, 2a and
      2b, displayed vasorelaxing effects, due to the release of NO, and antagonized the
      vasocontractile effects of angiotensin II, with potency values similar to that of
      losartan. In vivo, the antihypertensive effects of 2a were similar to those of
      losartan and captopril.

PMID- 15509156
TI  - Application of ALOGPS 2.1 to predict log D distribution coefficient for Pfizer
      proprietary compounds.
AB  - Evaluation of the ALOGPS, ACD Labs LogD, and PALLAS PrologD suites to calculate
      the log D distribution coefficient resulted in high root-mean-squared error
      (RMSE) of 1.0-1.5 log for two in-house Pfizer's log D data sets of 17,861 and 640
      compounds. Inaccuracy in log P prediction was the limiting factor for the overall
      log D estimation by these algorithms. The self-learning feature of the ALOGPS
      (LIBRARY mode) remarkably improved the accuracy in log D prediction, and an rmse
      of 0.64-0.65 was calculated for both data sets.

PMID- 15509157
TI  - A cyclopent-2-enecarbonyl group mimics proline at the P2 position of prolyl
      oligopeptidase inhibitors.
AB  - With the aim to replace the natural amino acid proline by a proline mimetic
      structure, a cyclopent-2-enecarbonyl moiety was studied at the P2 position of
      prolyl oligopeptidase (POP) inhibitors. The cyclopent-2-enecarbonyl moiety proved
      to be an excellent proline mimetic at the P2 position of POP inhibitors. The
      replacement is particularly useful when increased lipophilicity is needed.

PMID- 15509158
TI  - POT-DMC: A virtual screening method for the identification of potent hits.
AB  - A method for ligand-based virtual screening (LBVS), dynamic mapping of consensus
      positions (DMC), has been extended to take different potency levels of template
      compounds into account. This potency scaling technique is designed to tune search
      calculations toward the detection of increasingly potent hits. LBVS analysis of
      three different compound classes confirmed the ability of potency-scaled DMC (POT
      DMC) to identify active database compounds with higher potency than conventional
      calculations.

PMID- 15509159
TI  - Benzoxepin-derived estrogen receptor modulators: a novel molecular scaffold for
      the estrogen receptor.
AB  - We present and examine the efficacy of a novel benzoxepin-based scaffold for
      modulation of the human estrogen receptor. Receptor tolerance of this new
      molecular scaffold is examined through presentation of experimentally determined
      antiproliferative effects on human MCF-7 breast tumor cells and measured binding
      affinities. The effect of functional group substitution on the benzoxepin
      scaffold is explored through a brief computational structure-activity
      relationship investigation with molecular simulation.

PMID- 15509160
TI  - Toward a pharmacophore for kinase frequent hitters.
AB  - Small molecule protein kinase inhibitors are widely employed as biological
      reagents and as leads in the design of drugs for a variety of diseases. One of
      the hardest challenges in kinase inhibitor design is achieving target
      selectivity. By utilizing X-ray structural information for four promiscuous
      inhibitors, we propose a five-point pharmacophore for kinase frequent hitters,
      demonstrate its ability to discriminate between frequent hitters and selective
      ligands, and suggest a strategy for selective inhibitor design.

PMID- 15509161
TI  - Novel secoergoline derivatives inhibit both GABA and glutamate uptake in rat
      brain homogenates: synthesis, in vitro pharmacology, and modeling.
AB  - Three of twelve secoergoline derivatives (Z ethyl 4
      [(ethoxycarbonylmethyl)methylamino]-2-methyl-3-phenylpent-2-enoate, 8; ethyl 1,6
      dimethyl-3-oxo-5-phenyl-1,2,3,6-tetrahydropyridine-2-carboxylate, 9; Z methyl 4
      [(methoxycarbonylmethyl)methylamino)-2-methyl-3-phenylpent-2-enoate, 11),
      containing bioisosteric sequences of GABA and Glu, inhibited both GABA and Glu
      transport through cerebrocortical membranes specifically. Compounds 8, 9, and 11
      appeared to be equipotent inhibitors of GABA and Glu transport with IC50 values
      between 270 and 1100 microM, whereas derivatives 1-7, 10, and 12 were without
      effects. In the presence of GABA and Glu transport-specific nontransportable
      inhibitors, inhibition of GABA and Glu transport by 8, 9, and 11 proceeded in two
      phases. The two phases of inhibition were characterized by IC50 values between 4
      and 180 nM and 360-1020 microM and different selectivity sequences. These
      findings may indicate the existence of some mechanism possibly mediated by a
      previously unrecognized GABA-Glu transporter. Derivatives with the cis, but not
      the trans configuration of bulky ester groups (8 vs 7 and 11 vs 12) showed
      significant inhibitory effect (IC50 values of 270 microM vs >>1000 microM and
      1100 microM vs >>1000 microM on GABA transport, respectively). The cis-trans
      selectivity can be explained by docking these secoergolines in a three
      dimensional model of the second and third transmembrane helices of GABA
      transporter type 1.

PMID- 15509162
TI  - Chemical adaptor immunotherapy: design, synthesis, and evaluation of novel
      integrin-targeting devices.
AB  - A series of beta-diketone derivatives of RGD peptidomimetics that selectively
      bind to alphavbeta3 and alphavbeta5 integrins were synthesized and covalently
      docked to the reactive lysine residues of monoclonal aldolase antibody 38C2. The
      resulting targeting devices strongly and selectively bound to human cancer cells
      expressing integrins alphavbeta3 and alphavbeta5 as analyzed by flow cytometry.
      In vitro and in vivo studies revealed that these novel integrin-targeting devices
      efficiently inhibit tumor growth. Thus, the combination of beta-diketone
      derivatives of RGD peptidomimetics that target cell surface integrins alphavbeta3
      and alphavbeta5 with monoclonal aldolase antibodies through formation of a
      covalent bond of defined stoichiometry holds promise as a new approach to cancer
      therapy.

PMID- 15509163
TI  - 4,5-dihydro-1H-pyrazole derivatives with inhibitory nNOS activity in rat brain:
      synthesis and structure-activity relationships.
AB  - In an attempt to find new compounds with neuroprotective activity, we have
      designed, synthesized and characterized 19 new nNOS inhibitors with a 4,5-dihydro
      1H-pyrazole structure. Compounds 11r [1-cyclopropanecarbonyl-3-(2-amino-5
      chlorophenyl)-4,5-dihydro-1H-pyrazole] and 11e [1-cyclopropanecarbonyl-3-(2-amino
      5-methoxyphenyl)- 4,5-dihydro-1H-pyrazole] show the highest activities with
      inhibition percentages of 70% and 62%, respectively. A structure-activity
      relationship for the nNOS inhibition can be established from the structural
      comparison of these new pyrazole derivatives and the described synthetic
      kynurenines 10.

PMID- 15509164
TI  - Synthesis and anticancer activity of simplified indenoisoquinoline topoisomerase
      I inhibitors lacking substituents on the aromatic rings.
AB  - The indenoisoquinolines are a class of cytotoxic topoisomerase I inhibitors that
      offer certain advantages over the camptothecins, including the greater
      stabilities of the compounds themselves, as well as the greater stabilities of
      their drug-enzyme-DNA cleavage complexes. To investigate the possible biological
      roles of the di(methoxy) and methylenedioxy substituents present on the aromatic
      rings of the previously synthesized indenoisoquinoline topoisomerase I
      inhibitors, a series of compounds lacking these substituents was synthesized and
      tested for both cytotoxicity in cancer cell cultures and for enzyme inhibitory
      activity. The results indicate that the aromatic substituents make a small, but
      consistently observable contribution to the biological activity. Molecular models
      derived for the binding of the unsubstituted indenoisoquinolines in ternary
      complex with DNA and topoisomerase I indicate that the substituents on the lactam
      nitrogen project out of the major groove, and the carbonyl group is directed out
      of the minor groove, where it is involved in a hydrogen bonding interaction with
      the side chain guanidine group of Arg364. The DNA cleavage patterns observed in
      the presence of topoisomerase I and various indenoisoquinolines were similar,
      although significant differences were detected. There were also variations in the
      DNA cleavage pattern seen with camptothecin vs the indenoisoquinolines, which
      indicates that these two classes of topoisomerase I inhibitors are likely to
      target the cancer cell genome differently, resulting in different spectra of
      anticancer activity. The most cytotoxic of the presently synthesized
      indenoisoquinolines has a 4-amino-n-butyl group on the lactam nitrogen.

PMID- 15509165
TI  - Structural characterization and pharmacology of a potent (Cys101-Cys119, Cys110
      Cys117) bicyclic agouti-related protein (AGRP) melanocortin receptor antagonist.
AB  - Agouti-related protein (AGRP) is one of two known naturally occurring antagonists
      of G-protein coupled receptors. AGRP is synthesized in the brain and is an
      antagonist of the melanocortin-3 and -4 receptors (MC3R, MC4R). These three
      proteins are involved in the regulation of energy homeostasis and obesity in both
      mice and humans. The human AGRP protein is 132 amino acids and contains five
      disulfide bridges in the C-terminal domain. Previous reports of the NMR
      structures of hAGRP(87-132) and a truncated 34 amino acid form consisting of four
      disulfide bridges identified that AGRP contains an inhibitor cystine knot (ICK)
      structural fold, and that is the first mammalian example. Herein, we report a
      bicyclic hAGRP analogue that, when compared to hAGRP(87-132), possesses equal
      binding affinity but is 80-fold less potent at the mouse MC4R. Using NMR,
      computer assisted molecular modeling (CAMM), and cluster analysis, we have
      identified five structural families, two of which are highly populated, of this
      bicyclic hAGRP analogue. Computational docking experiments of this bicyclic hAGRP
      derivative, using a three-dimensional homology molecular model of the mouse MC4R,
      identified that three of the five structural families could be docked into the
      MC4R without problems from steric hindrance. Those three docked mMC4R-bicyclic
      hAGRP family structures were compared with putative hAGRP(87-132) ligand-receptor
      interactions previously reported (Wilczynski et al. J. Med. Chem. 2004, 47, 2194)
      in attempts to identify a "bioactive" conformation of the bicyclic hAGRP peptide
      and account for the 80-fold decreased ligand potency compared to hAGRP(87-132).

PMID- 15509166
TI  - Synthesis and biological evaluation of novel membrane-permeant cyclic ADP-ribose
      mimics: N1-[(5''-O-phosphorylethoxy)methyl]-5'-O-phosphorylinosine 5',5''
      cyclicpyrophosphate (cIDPRE) and 8-substituted derivatives.
AB  - N1-[(5' '-O-Phosphorylethoxy)methyl]-5'-O-phosphorylinosine 5',5''
      cyclicpyrophosphate (cIDPRE 2a) and the 8-substituted derivatives 8-bromo-, 8
      azido-, 8-amino-, and 8-Cl-cIDPRE (2b-e) were synthesized from N1-[(5''
      acetoxyethoxy)methyl]-2',3'-O-isopropylideneinosine (5) in good yields. The
      pharmacological activities of cIDPRE and the 8-substituted derivatives (2a-e)
      were analyzed in intact and permeabilized human Jurkat T-lymphocytes. The results
      indicate that cIDPRE permeates the plasma membrane, releases Ca2+ from an
      intracellular, cADPR-sensitive Ca2+ store, and subsequently initiates Ca2+
      release-activated Ca2+ entry. The Ca(2+)-releasing activity of cIDPRE was
      confirmed directly in permeabilized cells. Using time-resolved confocal Ca2+
      imaging at the single cell level, the development of global Ca2+ signals starting
      from local small Ca2+ signals evoked by cIDPRE was observed. 8-N3-cIDPRE 2c and 8
      NH2-cIDPRE 2d were similarly effective in their agonistic activity as compared to
      cIDPRE 2a, showing almost indistinguishable concentration-response curves for 2a,
      2c, and 2d and very similar kinetics of Ca2+ signaling. In contrast, the
      halogenated derivatives 8-Br- and 8-Cl-cIDPRE (2b and 2e) did not significantly
      elevate [Ca2+]i. Therefore, cIDPRE 2a, 8-N3-cIDPRE 2c, and 8-NH2-cIDPRE 2d are
      novel membrane permeant cADPR mimic and may provide important novel tools to
      study cADPR-mediated Ca2+ signaling in intact cells.

PMID- 15509167
TI  - A novel design strategy for stable metal complexes of nitrogen mustards as
      bioreductive prodrugs.
AB  - Tumor hypoxia provides a key difference between healthy and cancerous cells. It
      can be exploited to produce drug selectivity, offering a reductase-rich
      environment for prodrug activation. Nitrogen mustard drugs are cytotoxic, but
      usually unselective. Polyamine mustards are candidates for conversion into
      hypoxia-selective prodrugs via complexation with metals. Reduction to a less
      stable complex can free the active drug. The novel Cu(II) complexes of N-mustard
      derivatives of 1,4,7-triazacyclononane (tacn), 1,4,7,10-tetraazacyclododecane
      (cyclen), and 1,4,8,11-tetraazacyclotetradecane (cyclam) were assessed in vitro
      as hypoxia-selective cytotoxins. The cyclen mustard complex showed 24-fold
      selectivity as a hypoxia-selective bioreductive prodrug, with an IC50 value of 2
      microM against the lung tumor cell line A549. Reversible redox behavior and
      stability of the cyclen-Cu(II) complex in aqueous solution correlated with good
      hypoxia selectivity. The two other related complexes showed irreversible redox
      behavior and low aqueous stability and were not hypoxia-selective. The use of
      macrocyclic nitrogen mustard complexes represents a promising new strategy in the
      design of hypoxia-selective cytotoxins.

PMID- 15509168
TI  - Studies of targeting and intracellular trafficking of an anti-androgen
      doxorubicin-formaldehyde conjugate in PC-3 prostate cancer cells bearing androgen
      receptor-GFP chimera.
AB  - The synthesis of a doxorubicin-formaldehyde conjugate bound to the nonsteroidal
      anti-androgen cyanonilutamide, via a cleavable tether, and binding of the
      construct to cell free androgen receptor (AR) as a function of tether design were
      previously reported. Cyanonilutamide bearing a linear alkyne tether bound to the
      AR better than other designs. Fluorescence microscopy studies of binding of the
      lead targeted drug, as well as various tethered cyanonilutamides, to the AR and
      subsequent trafficking of the resulting AR complex in live PC3 prostate cancer
      cells transfected with AR-green fluorescent protein (GFP) chimera are now
      described. Cyanonilutamide and cyanonilutamide bonded to a linear alkyne tether
      caused translocation of AR-GFP to the nucleus. In general, the ability of
      tethered cyanonilutamides to cause translocation paralleled their binding
      affinity for the AR. However, a noncleavable form of the lead cyanonilutamide
      doxorubicin-formaldehyde conjugate bound to AR-GFP but the resulting complex did
      not translocate to the nucleus. Binding was apparent from the drugs inhibition of
      Mibolerone-induced translocation. Direct observation of anthraquinone
      fluorescence of targeted drug in PC3 cells showed initial cytosolic localization,
      independent of AR expression, with predominant nuclear localization after
      sufficient time for release of drug from the targeting moiety. The results
      indicate that doxorubicin-formaldehyde conjugate bonded to cyanonilutamide via a
      cleavable linear tether enters PC3 cells, resides in cytosol, binds to the AR if
      present, and ultimately releases doxorubicin or a doxorubicin derivative to the
      nucleus.

PMID- 15509169
TI  - Synthesis, conformational analysis, and cytotoxicity of conformationally
      constrained aplidine and tamandarin A analogues incorporating a spirolactam beta
      turn mimetic.
AB  - With the aim of studying the contribution of the beta II turn conformation at the
      side chain of didemnins to the bioactive conformation responsible for their
      antitumoral activity, conformationally restricted analogues of aplidine and
      tamandarin A, where the side chain dipeptide Pro8-N-Me-d-Leu7 is replaced with
      the spirolactam beta II turn mimetic (5R)-7-[(1R)-1-carbonyl-3-methylbutyl]-6-oxo
      1,7-diazaspiro[4.4]nonane, were prepared. Additionally, restricted analogues,
      where the aplidine (pyruvyl9) or tamandarin A [(S)-Lac9] acyl groups are replaced
      with the isobutyryl, Boc, and 2-methylacryloyl groups, were also prepared. These
      structural modifications were detrimental to cytotoxic activity, leading to a
      decrease of 1-2 orders of magnitude with respect to that exhibited by aplidine
      and tamandarin A. The conformational analysis of one of these spirolactam
      aplidine analogues, by NMR and molecular modeling methods, showed that the
      conformational restriction caused by the spirolactam does not produce significant
      changes in the overall conformation of aplidine, apart from preferentially
      stabilizing the trans rotamer at the pyruvyl9-spirolactam amide bond, whereas in
      aplidine both cis and trans rotamers at the pyruvyl9-Pro8 amide bond are more or
      less equally stabilized. These results seem to indicate a preference for the cis
      form at that amide bond in the bioactive conformation of aplidine. The
      significant influence of this cis/trans isomerism upon the cytotoxicity suggests
      a possible participation of a peptidylprolyl cis/trans isomerase in the mechanism
      of action of aplidine.

PMID- 15509170
TI  - Structure-based exploration of cyclic dipeptide chitinase inhibitors.
AB  - Family 18 chitinases play an essential role in a range of pathogens and pests.
      Several inhibitors are known, including the potent inhibitors argadin and
      allosamidin, and the structures of these in complex with chitinases have been
      elucidated. Recent structural analysis has revealed that CI-4 [cyclo-(L-Arg-D
      Pro)] inhibits family 18 chitinases by mimicking the structure of the proposed
      reaction intermediate. Here we report the high-resolution structures of four new
      CI-4 derivatives, cyclo-(L-Arg-L-Pro), cyclo-(Gly-L-Pro), cyclo-(L-His-L-Pro),
      and cyclo-(L-Tyr-L-Pro), in complex with a family 18 chitinase. In addition,
      details of enzyme inhibition and in vivo activity against Saccharomyces
      cerevisiae are presented. The structures reveal that the common cyclo-(Gly-Pro)
      substructure is sufficient for binding, allowing modification of the side chain
      of the nonproline residue. This suggests that design of cyclic dipeptides with a
      view to increasing inhibition of family 18 chitinases should be possible through
      relatively accessible chemistry. The derivatives presented here in complex with
      chitinase B from Serratia marcescens provide further insight into the mechanism
      of inhibition of chitinases by cyclic dipeptides as well as providing a new
      scaffold for chitinase inhibitor design.

PMID- 15509171
TI  - Distance of hydroxyl functionality from the quaternized center influence DNA
      binding and in vitro gene delivery efficacies of cationic lipids with
      hydroxyalkyl headgroups.
AB  - In vitro gene delivery efficacies of cationic amphiphiles 1-7 (Scheme 1) were
      measured by both the reporter gene expression assays in CHO, COS-1, HepG2, and
      MCF7 cells and by the whole cell histochemical X-gal staining of representative
      Chinese hamster ovary cells. Our results demonstrated that in vitro gene delivery
      efficiencies of cationic lipids with hydroxyalkyl headgroups are adversely
      affected by increased covalent distances between the hydroxyl functionality and
      the cationic centers. Findings in the DNase I protection experiments and
      transmission electron microscopic study support the notion that such compromised
      gene delivery efficacies may originate from poor lipid-DNA binding interactions
      and significantly increased lipoplex nanosizes.

PMID- 15509172
TI  - Structural selectivity of aromatic diamidines.
AB  - Competition dialysis was used to study the interactions of 13 substituted
      aromatic diamidine compounds with 13 nucleic acid structures and sequences. The
      results show a striking selectivity of these compounds for the triplex structure
      poly dA:(poly dT)2, a novel aspect of their interaction with nucleic acids not
      previously described. The triplex selectivity of selected compounds was confirmed
      by thermal denaturation studies. Triplex selectivity was found to be modulated by
      the location of amidine substituents on the core phenyl-furan-phenyl ring
      scaffold. Molecular models were constructed to rationalize the triplex
      selectivity of DB359, the most selective compound in the series. Its triplex
      selectivity was found to arise from optimal ring stacking on base triplets, along
      with proper positioning of its amidine substituents to occupy the minor and the
      major-minor grooves of the triplex. New insights into the molecular recognition
      of nucleic acid structures emerged from these studies, adding to the list of
      available design principles for selectively targeting DNA and RNA.

PMID- 15509173
TI  - Synthesis and antiviral evaluation of polyhalogenated imidazole nucleosides:
      dimensional analogues of 2,5,6-trichloro-1-(beta-D-ribofuranosyl)benzimidazole.
AB  - A series of polyhalogenated imidazole nucleosides were designed and synthesized
      as ring-contracted analogues of 2,5,6-trichloro-1-(beta-D
      ribofuranosyl)benzimidazole (TCRB) and its 2-bromo analogue (BDCRB) in an effort
      to explore the spatial limitation of the active pocket(s) in the target
      protein(s). 2,4,5-Trichloro-, 2-bromo-4,5-dichloro-, and 2,4,5-tribromoimidazole
      nucleosides were prepared by a condensation of the preformed heterocycles with
      the appropriate sugar precursors. The ribofuranosyl and xylofuranosyl analogues
      were prepared by a direct glycosylation using the Vorbruggen's silylation method
      and provided exclusively the beta-anomers. The arabinofuranosyl analogues were
      prepared by the sodium salt method to give both the alpha- and beta-anomers. The
      absolute configurations were established by 1H NMR spectroscopy. Alkylation of
      the polyhalogenated imidazoles with the appropriate bromomethyl ethers gave the
      acyclic acyclovir and ganciclovir analogues. In general, the parent
      polyhalogenated imidazoles showed some activity against human cytomegalovirus
      (HCMV) (IC50 approximately 35 microM). However, with the exception of two
      tribromo analogues (7c, 13c-beta), most of their nucleoside derivatives were
      inactive against both HCMV and herpes simplex virus type-1 (HSV-1) and were not
      cytotoxic. The results suggest that the ring-contracted nucleoside analogues of
      TCRB and BDCRB interacted weakly or not at all with viral and cellular targets.

PMID- 15509174
TI  - Design, synthesis, and antiviral activity of certain 3-substituted 2,5,6
      trichloroindole nucleosides.
AB  - A series of trichlorinated indole nucleosides has been synthesized and tested for
      activity against human cytomegalovirus (HCMV) and herpes simplex virus type-1
      (HSV-1) and for cytotoxicity. Modifications of the previously reported 2,5,6
      trichloro-1-(beta-d-ribofuranosyl)indole at the 3-position of the heterocycle
      were designed in part to test our hypothesis that hydrogen bonding is required at
      that position for antiviral activity. Analogues were synthesized using
      electrophilic addition at the 3-position or by synthesis of modified indole
      heterocycles followed by glycosylation and modification of the sugar. Among the
      modifications at the 3-position, only those analogues with hydrogen-bond
      accepting character were active against HCMV (e.g., 3-formyl-2,5,6-trichloro-1
      (beta-D-ribofuranosyl)indole, FTCRI, IC50 = 0.23 microM). Conversely, analogues
      with non-hydrogen-bonding substituents at the 3-position (e.g., 3-methyl-2,5,6
      trichloro-1-(beta-D-ribofuranosyl)indole) were much less active (IC50 = 32
      microM) than those with the requisite hydrogen-bonding capacity. The 5'-O-acyl
      analogue of FTCRI was obtained as an intermediate and also found to be a potent
      inhibitor of HCMV (IC50 < 0.1 microM). The synthesis of some additional 5'-O
      acylated analogues did not provide a compound with increased antiviral activity.
      None of the indole nucleosides had significant activity against HSV-1, and none
      were cytotoxic to uninfected cells in their antiviral dose range. Results
      obtained from the antiviral evaluations have validated our hypothesis that
      hydrogen bonding at the 3-position is required for antiviral activity in this
      series of chlorinated indole nucleosides.

PMID- 15509175
TI  - Synthesis and antiviral activity of 3-formyl- and 3-cyano-2,5,6-trichloroindole
      nucleoside derivatives.
AB  - A series of trichlorinated indole nucleosides has been synthesized and tested for
      activity against human cytomegalovirus (HCMV) and herpes simplex virus type-1
      (HSV-1) and for cytotoxicity. The previously reported 3-formyl-2,5,6-trichloro-1
      (beta-D-ribofuranosyl)indole (FTCRI) and its 3-cyano homologue (CTCRI) were
      chemically modified at the 3-position. The formation of hydrazones and oximes of
      FTCRI was accomplished by a dehydrative addition of the appropriate hydrazine or
      hydroxylamine derivatives, respectively. A carboxamide oxime and imidate were
      synthesized from CTCRI by the addition of hydroxylamine or methanol,
      respectively, to the 3-nitrile substituent. Analogues synthesized from FTCRI
      generally had less antiviral activity than either FTCRI or CTCRI. However, the
      derivatives of CTCRI were potent and selective inhibitors of HCMV in vitro. The
      analogue 2,5,6-trichloro-1-(beta-D-ribofuranosyl)indole-3-carboxamide oxime was
      especially selective (HCMV IC50 = 0.30 microM, CC50 > 100 microM). None of the
      analogues had significant activity against HSV-1.

PMID- 15509176
TI  - Synthesis, antiviral activity, and mode of action of some 3-substituted 2,5,6
      trichloroindole 2'- and 5'-deoxyribonucleosides.
AB  - A series of chlorinated indole nucleosides has been synthesized and tested for
      activity against human cytomegalovirus (HCMV) and herpes simplex virus type-1
      (HSV-1) and for cytotoxicity. The 2'- and 5'-deoxy derivatives of the reported 3
      formyl-2,5,6-trichloro-1-(beta-D-ribofuranosyl)indole (FTCRI) and 3-cyano-2,5,6
      trichloro-1-(beta-D-ribofuranosyl)indole (CTCRI) were synthesized by either a
      modification of the appropriate 3-unsubstituted sugar-modified nucleoside
      analogues or by a glycosylation of 3-substituted heterocycles with a protected
      alpha-chlorosugar. The modifications were guided in part by structural similarity
      to the corresponding series of chlorinated benzimidazole ribonucleosides and the
      fact that 5'-deoxy analogues of 2,5,6-trichloro-1-(beta-D
      ribofuranosyl)benzimidazole (TCRB) are very active against HCMV. The 5'-deoxy
      analogues of FTCRI and CTCRI were nearly as active as FTCRI and CTCRI, suggesting
      that the chlorinated benzimidazole nucleosides and the chlorinated indole
      nucleosides act in a similar manner. This hypothesis was supported by time-of
      addition studies using FTCRI and by the resistance of TCRB-resistant strains of
      HCMV to four different 3-substituted indole ribonucleosides. The 2'-deoxy
      analogues of the trichlorinated indole nucleosides also had potent antiviral
      activity, in contrast to decreased activity and selectivity observed for 2'-deoxy
      TCRB compared to TCRB. In addition, 3-acetyl-2,5,6-trichloro-1-(2-deoxy-beta-d
      ribofuranosyl)indole was also active and much less cytotoxic (HCMV IC50 = 0.30
      microM, HFF CC50 >100 microM) than previous analogues. None of the analogues had
      significant activity against HSV-1.

PMID- 15509177
TI  - Synthesis, structure-activity relationships, and in vivo properties of 3,4
      dihydro-1H-pyrido[2,3-b]pyrazin-2-ones as corticotropin-releasing factor-1
      receptor antagonists.
AB  - Corticotropin releasing factor (CRF) is the primary regulator of the hypothalamus
      pituitary-adrenal (HPA) axis, coordinating the endocrine, behavioral, and
      autonomic responses to stress. It has been postulated that small molecules that
      can antagonize the binding of CRF1 to its receptor may serve as a treatment for
      anxiety-related and/or affective disorders. Members within a series of 3,4
      dihydro-1H-pyrido[2,3-b]pyrazin-2-ones, exemplified by compound 2 (IC50 = 0.70
      nM), were found to be very potent antagonists of CRF1. Compound 8w showed high
      CRF1 receptor binding affinity and was examined further in vivo. The compound was
      efficacious in a defensive withdrawal model of anxiety in rats and had a long
      half-life and reasonable oral bioavailability in dog pharmacokinetic studies.

PMID- 15509178
TI  - Efficient evaluation of binding free energy using continuum electrostatics
      solvation.
AB  - The linear interaction energy (LIE) method is combined with energy minimization
      and finite-difference Poisson calculation of electrostatic solvation for the
      estimation of the absolute free energy of binding. A predictive accuracy of about
      1.0 kcal/mol is obtained for 13 and 29 inhibitors of beta-secretase (BACE) and
      HIV-1 protease (HIV-1 PR), respectively. The multiplicative coefficients for the
      van der Waals and electrostatic terms are not transferable between BACE and HIV-1
      PR although they are both aspartic proteases. The present approach is about 2
      orders of magnitude faster than previous LIE methods and can be used for ranking
      large libraries of structurally diverse compounds docked by automatic
      computational tools.

PMID- 15509179
TI  - Design and synthesis of novel N-acetylgalactosamine-terminated glycolipids for
      targeting of lipoproteins to the hepatic asialoglycoprotein receptor.
AB  - A novel glycolipid has been prepared that contains a cluster glycoside with an
      unusually high affinity for the asialoglycoprotein receptor (ASGPr) and a bile
      acid moiety that mediates stable incorporation into lipidic particles. The
      glycolipid spontaneously associated with low-density lipoproteins (LDL) and high
      density lipoproteins (HDL) within human and murine plasma, and loading of
      lipoproteins with this glycolipid resulted in an efficient dose-dependent
      recognition and uptake of LDL and HDL by the liver (and not by spleen) upon
      intravenous injection into wild-type mice. Preinjection with asialoorosomucoid
      largely inhibited the uptake, establishing that both HDL and LDL were selectively
      recognized and processed by the ASGPr on liver parenchymal cells. Finally,
      repeated intravenous administration of the glycolipid to hyperlipidemic LDL
      receptor-deficient mice evoked an efficient and persistent cholesterol-lowering
      effect. These results indicate that the glycolipid may be a promising alternative
      for the treatment of hyperlipidemic patients who do not respond sufficiently to
      current cholesterol-lowering therapies.

PMID- 15509180
TI  - Design, chemical synthesis, and biological evaluation of thiosaccharide analogues
      of morphine- and codeine-6-glucuronide.
AB  - A series of 6-beta-thiosaccharide analogues of morphine-6-glucuronide (M6G) and
      codeine-6-glucuronide (C6G) were synthesized and evaluated with the objective of
      preparing an analogue of M6G with improved biological activity. The affinity of
      the thiosaccharide analogues of M6G and C6G was examined by competitive binding
      assays at mu, delta, and kappa opioid receptors. The thiosaccharide compounds in
      the morphine series 5b, 5e, 6a, and 6c showed 1.5-2.4-fold higher affinity for
      the mu receptor than M6G, but were generally less selective than M6G. The
      functional activity of the M6G and C6G analogues was examined with the [35S]GTP
      gamma-S assay. Compounds 5b and 5e were determined to be full mu agonists,
      whereas compounds 6a and 6c were partial mu agonists. The in vivo antinociceptive
      activity of compound 5b was evaluated by the tail flick latency test, giving an
      ED50 of 2.5 mg/kg.

PMID- 15509181
TI  - Antitumor Agents. 239. Isolation, structure elucidation, total synthesis, and
      anti-breast cancer activity of neo-tanshinlactone from Salvia miltiorrhiza.
AB  - Neo-tanshinlactone (1) was isolated and synthesized for the first time and
      evaluated in vitro against several human cancer cell lines. Compound 1 showed
      significant inhibition against two ER+ human breast cancer cell lines and was 10
      fold more potent and 20-fold more selective as compared to tamoxifen citrate.
      Compound 1 also potently inhibited an ER-, HER-2 overexpressing breast cancer
      cell line. Therefore, this novel compound merits further development as an anti
      breast cancer drug candidate.

PMID- 15509182
TI  - Pharmacokinetics of tocolytic agents.
AB  - Tocolytic agents are drugs designed to inhibit contractions of myometrial smooth
      muscle cells. Such an effect has been demonstrated in vitro or in vivo for
      several pharmacological agents, including beta-adrenergic agonists, calcium
      channel antagonists, oxytocin antagonists, NSAIDs and magnesium sulfate. However,
      the aim of tocolysis is not only to stop uterine contractions or to prevent
      preterm delivery, but to prevent perinatal morbidity and mortality associated
      with preterm birth. The achievement of this goal has not yet been clearly
      demonstrated for any of the drugs available, and the use of tocolytic agents may
      appear controversial. Therefore, it is important to avoid maternal and fetal
      toxicity when tocolytic agents are used. During pregnancy, all steps of drug
      pharmacokinetics are altered. Absorption of drugs administered orally is limited
      because of delayed stomach emptying and reduced intestinal motility. The volume
      of distribution of drugs is increased. The metabolic activity of the liver is
      increased, accelerating the metabolism of lipophilic drugs. Renal filtration is
      increased, leading to enhanced renal elimination of water-soluble drugs. These
      modifications are generally responsible for reduced plasma concentration and
      reduced half-life of most drugs. These specific modifications have to be taken
      into account when using a drug in pregnant women. The aim of this review is to
      provide the reader with pharmacological data about drugs currently used to treat
      preterm labour. Such data in pregnant women may affect the choice of optimal drug
      dosage and route of administration.

PMID- 15509183
TI  - Practical guidelines to interpret plasma concentrations of antiretroviral drugs.
AB  - Several relationships have been reported between antiretroviral drug
      concentrations and the efficacy of treatment, and toxicity. Therefore,
      therapeutic drug monitoring (TDM) may be a valuable tool in improving the
      treatment of HIV-1-infected patients in daily practice. In this regard, several
      measures of exposure have been studied, e.g. trough and maximum concentrations,
      concentration ratios and the inhibitory quotient. However, it has not been
      unambiguously established which pharmacokinetic parameter should be monitored to
      maintain optimal viral suppression. Each pharmacokinetic parameter has its pros
      and cons. Many factors can affect the pharmacokinetics of antiretroviral agents,
      resulting in variability in plasma concentrations between and within patients.
      Therefore, plasma concentrations should be considered on several occasions. In
      addition, the interpretation of the drug concentration of a patient should be
      performed on an individual basis, taking into account the clinical condition of
      the patient. Important factors herewith are viral load, immunology, occurrence of
      adverse events, resistance pattern and comedication. In spite of the described
      constraints, the aim of this review is to provide a practical guide for TDM of
      antiretroviral agents. This article outlines pharmacokinetic target values for
      the HIV protease inhibitors amprenavir, atazanavir, indinavir, lopinavir,
      nelfinavir, ritonavir and saquinavir, and the non-nucleoside reverse
      transcriptase inhibitors efavirenz and nevirapine. Detailed advice is provided on
      how to interpret the results of TDM of these drugs.

PMID- 15509184
TI  - Bicalutamide: clinical pharmacokinetics and metabolism.
AB  - Bicalutamide is a nonsteroidal pure antiandrogen given at a dosage of 150 mg once
      daily as monotherapy for the treatment of early (localised or locally advanced)
      nonmetastatic prostate cancer. It is used at a dosage of 50 mg once daily in
      combination with a luteinising hormone-releasing hormone analogue or surgical
      castration for the treatment of advanced prostate cancer. Bicalutamide is a
      racemate and its antiandrogenic activity resides almost exclusively in the (R)
      enantiomer, with little, if any, activity in the (S)-enantiomer. (R)-Bicalutamide
      is slowly and saturably absorbed, but absorption is unaffected by food. It has a
      long plasma elimination half-life (1 week) and accumulates about 10-fold in
      plasma during daily administration. (S)-Bicalutamide is much more rapidly
      absorbed and cleared from plasma; steady-state concentrations (Css) of (R)
      bicalutamide are 100-fold higher than those of (S)-bicalutamide. Css increases
      linearly with doses up to 50 mg, but nonlinearly at higher doses, reaching a
      plateau above 300 mg. Css is higher in Japanese than in Caucasians, but no
      relationship with degree of renal impairment, bodyweight or age exists. Although
      mild-to-moderate hepatic impairment does not affect pharmacokinetics, there is
      evidence for slower elimination of (R)-bicalutamide in subjects with severe
      hepatic impairment. Bicalutamide metabolites are excreted almost equally in urine
      and faeces with little or no unchanged drug excreted in urine; conversely,
      unchanged drug predominates in plasma. Bicalutamide in faeces is thought to arise
      from hydrolysis of bicalutamide glucuronide and from unabsorbed drug.
      Bicalutamide appears to be cleared almost exclusively by metabolism; this is
      largely mediated by cytochrome P450 (CYP) for (R)-bicalutamide, but
      glucuronidation is the predominant metabolic route for (S)-bicalutamide. (S)
      Bicalutamide is metabolised in vitro by CYP3A4, and it is probable that this
      isoenzyme is also responsible for the metabolism of (R)-bicalutamide. In vitro
      data suggest that (R)-bicalutamide has the potential to inhibit CYP3A4 and, to a
      lesser extent, CYP2C9, 2C19 and 2D6. However, using midazolam as a specific
      CYP3A4 marker, no clinically relevant inhibition is observed in vivo with
      bicalutamide 150mg. Although bicalutamide is a CYP inducer in laboratory animals,
      dosages < or = 150 mg/day have shown no evidence of enzyme induction in humans.
      Daily administration of bicalutamide increases circulating levels of
      gonadotrophins and sex hormones; although testosterone increases by up to 80%,
      concentrations in most patients remain within the normal range. Bicalutamide
      produces a dose-related decrease in prostate-specific antigen (PSA) at dosages <
      or = 150 mg/day. However, little relationship is observed between median PSA
      reduction and (R)-bicalutamide Css.

PMID- 15509187
TI  - Effect of colesevelam HCl on single-dose fenofibrate pharmacokinetics.
AB  - OBJECTIVE: The primary aim of this study was to determine whether there is an
      effect of colesevelam HCl (WelChol; Sankyo Pharma Inc., Parsippany, NJ, USA) on
      fenofibric acid (active metabolite of fenofibrate, TriCor, Abbott Laboratories,
      North Chicago, IL, USA) pharmacokinetics following single-dose fenofibrate when
      colesevelam HCl and fenofibrate are administered concomitantly, or when
      colesevelam HCl is administered 4 hours following fenofibrate therapy. METHODS:
      Thirty healthy volunteers were enrolled in a randomised, open-label, three-way
      crossover, drug interaction study. Subjects received one of three treatments at
      each of three dose administration periods: (i) treatment A -- fenofibrate 160 mg
      plus colesevelam HCl 3750 mg (6 x 625 mg tablets) administered with breakfast;
      (ii) treatment B -- fenofibrate 160 mg administered with breakfast, followed 4
      hours later by colesevelam HCl 3750 mg (6 x 625 mg tablets) administered with
      lunch; or (iii) treatment C -- fenofibrate 160 mg administered with breakfast.
      Treatments were separated by a 10-day washout period. Blood samples were
      collected at predetermined time intervals, both before and after drug
      administration. Plasma concentrations of fenofibrate and fenofibric acid were
      measured using a validated liquid chromatography/mass spectroscopy/mass
      spectroscopy method. RESULTS: Area under the concentration-time curve (AUC) from
      time zero to the timepoint of the lowest quantifiable concentration (AUCt), AUC
      from time zero to infinity (AUCinfinity) and maximum plasma concentration (Cmax)
      for fenofibric acid were 92.1%, 93.9% and 79.8%, respectively, of control values
      when colesevelam HCl and fenofibrate were coadministered with breakfast; and
      91.9%, 93.9% and 99.1%, respectively, when fenofibrate was administered followed
      4 hours later by administration of colesevelam HCl. The 90% confidence intervals
      for the ratios of geometric means for AUCt, AUCinfinity and Cmax comparing the
      three treatments were contained within the 80-125% equivalence range, with the
      exception of Cmax for treatment A. Coadministration of fenofibrate with
      colesevelam HCl resulted in an approximate 20% reduction in Cmax of the active
      metabolite (fenofibric acid). There were no significant differences in the time
      to Cmax, elimination rate constant or elimination half-life between any of the
      treatment groups. CONCLUSIONS: Colesevelam HCl had no significant effect on
      fenofibrate bioavailability when administered either concomitantly with
      fenofibrate or 4 hours after fenofibrate.

PMID- 15509188
TI  - Ottawa Panel Evidence-Based Clinical Practice Guidelines for Electrotherapy and
      Thermotherapy Interventions in the Management of Rheumatoid Arthritis in Adults.
AB  - BACKGROUND AND PURPOSE: The purpose of this project was to create guidelines for
      electrotherapy and thermotherapy interventions in the management of adult
      patients (>18 years of age) with a diagnosis of rheumatoid arthritis according to
      the criteria of the American Rheumatism Association (1987). METHODS: Using
      Cochrane Collaboration methods, the Ottawa Methods Group identified and
      synthesized evidence from comparative controlled trials. The group then formed an
      expert panel, which developed a set of criteria for grading the strength of the
      evidence and the recommendation. Patient-important outcomes were determined
      through consensus, provided that these outcomes were assessed with a validated
      and reliable scale. RESULTS: The Ottawa Panel developed 8 positive
      recommendations of clinical benefit. Lack of evidence meant that the panel could
      not gauge the efficacy of electrical stimulation. DISCUSSION AND CONCLUSION: The
      Ottawa Panel recommends the use of low-level laser therapy, therapeutic
      ultrasound, thermotherapy, electrical stimulation, and transcutaneous electrical
      nerve stimulation for the management of rheumatoid arthritis.

PMID- 15509186
TI  - Pharmacodynamics of vancomycin and other antimicrobials in patients with
      Staphylococcus aureus lower respiratory tract infections.
AB  - BACKGROUND: Vancomycin is commonly used to treat staphylococcal infections, but
      there has not been a definitive analysis of the pharmacokinetics of this
      antibacterial in relation to minimum inhibitory concentration (MIC) that could be
      used to determine a target pharmacodynamic index for treatment optimisation.
      OBJECTIVE: To clarify relationships between vancomycin dosage, serum
      concentration, MIC and antimicrobial activity by using data gathered from a
      therapeutic monitoring environment that observes failures in some cases. METHODS:
      We investigated all patients with a Staphylococcus aureus lower respiratory tract
      infection at a 300-bed teaching hospital in the US during a 1-year period.
      Clinical and pharmacokinetic information was used to determine the following: (i)
      whether steady-state 24-hour area under the concentration-time curve (AUC24)
      divided by the MIC (AUC24/MIC) values for vancomycin could be precisely
      calculated with a software program; (ii) whether the percentage of time
      vancomycin serum concentrations were above the MIC (%Time>MIC) was an important
      determinant of vancomycin response; (iii) whether the time to bacterial
      eradication differed as the AUC24/MIC value increased; (iv) whether the time to
      bacterial eradication for vancomycin differed compared with other antibacterials
      at the same AUC24/MIC value; and (v) whether a relationship existed between time
      to bacterial eradication and time to significant clinical improvement of
      pneumonia symptoms. RESULTS: The median age of the 108 patients studied was 74
      (range 32-93) years. Measured vancomycin AUC24/MIC values were precisely
      predicted with the A.U.I.C. calculator in a subset of our patients (r2 = 0.935).
      Clinical and bacteriological response to vancomycin therapy was superior in
      patients with higher (> or = 400) AUC24/MIC values (p = 0.0046), but no
      relationship was identified between vancomycin %Time>MIC and infection response.
      Bacterial eradication of S. aureus (both methicillin-susceptible and methicillin
      resistant) occurred more rapidly (p = 0.0402) with vancomycin when a threshold
      AUC24/MIC value was reached. S. aureus killing rates were slower with vancomycin
      than with other antistaphylococcal antibacterials (p = 0.002). There was a
      significant relationship (p < 0.0001) between time to bacterial eradication and
      the time to substantial improvement in pneumonia score. CONCLUSIONS: Vancomycin
      AUC24/MIC values predict time-related clinical and bacteriological outcomes for
      patients with lower respiratory tract infections caused by methicillin-resistant
      S. aureus.

PMID- 15509189
TI  - A home program of sensory and neuromuscular electrical stimulation with upper
      limb task practice in a patient 5 years after a stroke.
AB  - BACKGROUND AND PURPOSE: This case report describes a person with upper-extremity
      (UE) hemiparesis who participated in a home program that included sensory
      amplitude electrical stimulation (SES) to his involved arm and performance of
      task-specific exercises with the assistance of neuromuscular electrical
      stimulation (NMES). CASE DESCRIPTION: The patient was a 67-year-old man with
      stable sensory and motor deficits 5 years after a stroke. Sensory amplitude
      electrical stimulation was delivered for 2 hours per day. A daily, 15-minute
      course of NMES was used to help him perform UE tasks. This home program was
      carried out for 18 weeks and included 6 physical therapist home visits. OUTCOMES:
      The patient's UE score on the Stroke Rehabilitation Assessment of Movement
      (STREAM) improved from 10/20 to 17/20. The score on the Action Research Arm Test
      (ARAT) improved from 27/57 to 42/57. The patient reported that he was now able to
      button buttons, use a knife and fork, and tie simple fishing knots. DISCUSSION: A
      home program combining SES and NMES may be an effective method to increase UE
      function even 5 years after a stroke.

PMID- 15509190
TI  - Thirty-Fifth Mary McMillan Lecture. Braving new worlds: to conquer, to endure.

PMID- 15509185
TI  - Clinical pharmacology of tramadol.
AB  - Tramadol, a centrally acting analgesic structurally related to codeine and
      morphine, consists of two enantiomers, both of which contribute to analgesic
      activity via different mechanisms. (+)-Tramadol and the metabolite (+)-O
      desmethyl-tramadol (M1) are agonists of the mu opioid receptor. (+)-Tramadol
      inhibits serotonin reuptake and (-)-tramadol inhibits norepinephrine reuptake,
      enhancing inhibitory effects on pain transmission in the spinal cord. The
      complementary and synergistic actions of the two enantiomers improve the
      analgesic efficacy and tolerability profile of the racemate. Tramadol is
      available as drops, capsules and sustained-release formulations for oral use,
      suppositories for rectal use and solution for intramuscular, intravenous and
      subcutaneous injection. After oral administration, tramadol is rapidly and almost
      completely absorbed. Sustained-release tablets release the active ingredient over
      a period of 12 hours, reach peak concentrations after 4.9 hours and have a
      bioavailability of 87-95% compared with capsules. Tramadol is rapidly distributed
      in the body; plasma protein binding is about 20%. Tramadol is mainly metabolised
      by O- and N-demethylation and by conjugation reactions forming glucuronides and
      sulfates. Tramadol and its metabolites are mainly excreted via the kidneys. The
      mean elimination half-life is about 6 hours. The O-demethylation of tramadol to
      M1, the main analgesic effective metabolite, is catalysed by cytochrome P450
      (CYP) 2D6, whereas N-demethylation to M2 is catalysed by CYP2B6 and CYP3A4. The
      wide variability in the pharmacokinetic properties of tramadol can partly be
      ascribed to CYP polymorphism. O- and N-demethylation of tramadol as well as renal
      elimination are stereoselective. Pharmacokinetic-pharmacodynamic characterisation
      of tramadol is difficult because of differences between tramadol concentrations
      in plasma and at the site of action, and because of pharmacodynamic interactions
      between the two enantiomers of tramadol and its active metabolites. The analgesic
      potency of tramadol is about 10% of that of morphine following parenteral
      administration. Tramadol provides postoperative pain relief comparable with that
      of pethidine, and the analgesic efficacy of tramadol can further be improved by
      combination with a non-opioid analgesic. Tramadol may prove particularly useful
      in patients with a risk of poor cardiopulmonary function, after surgery of the
      thorax or upper abdomen and when non-opioid analgesics are contraindicated.
      Tramadol is an effective and well tolerated agent to reduce pain resulting from
      trauma, renal or biliary colic and labour, and also for the management of chronic
      pain of malignant or nonmalignant origin, particularly neuropathic pain. Tramadol
      appears to produce less constipation and dependence than equianalgesic doses of
      strong opioids.

PMID- 15509191
TI  - The clinician's best friend.

PMID- 15509192
TI  - Is radiologic examination necessary for a 9-year-old girl with a knee injury?

PMID- 15509193
TI  - Expression of secretory phospholipase A2 enzymes in lungs of humans with
      pneumonia and their potential prostaglandin-synthetic function in human lung
      derived cells.
AB  - Although a number of sPLA2 (secretory phospholipase A2) enzymes have been
      identified in mammals, the localization and functions of individual enzymes in
      human pathologic tissues still remain obscure. In the present study, we have
      examined the expression and function of sPLA2s in human lung-derived cells and in
      human lungs with pneumonia. Group IID, V and X sPLA2s were expressed in cultured
      human bronchial epithelial cells (BEAS-2B) and normal human pulmonary fibroblasts
      with distinct requirement for cytokines (interleukin-1b, tumour necrosis factor a
      and interferon-g). Lentivirus- or adenovirus-mediated transfection of various
      sPLA2s into BEAS-2B or normal human pulmonary fibroblast cells revealed that
      group V and X sPLA2s increased arachidonate release and prostaglandin production
      in both cell types, whereas group IIA and IID sPLA2s failed to do so.
      Immunohistochemistry of human lungs with pneumonia demonstrated that group V and
      X sPLA2s were widely expressed in the airway epithelium, interstitium and
      alveolar macrophages, in which group IID sPLA2 was also positive, whereas group
      IIA sPLA2 was restricted to the pulmonary arterial smooth muscle layers and
      bronchial chondrocytes, and group IIE and IIF sPLA2s were minimally detected.
      These results suggest that group V and X sPLA2s affect lung pathogenesis by
      facilitating arachidonate metabolism or possibly through other functions.

PMID- 15509194
TI  - Identification and characterization of Sulfolobus solfataricus D-gluconate
      dehydratase: a key enzyme in the non-phosphorylated Entner-Doudoroff pathway.
AB  - The extremely thermoacidophilic archaeon Sulfolobus solfataricus utilizes D
      glucose as a sole carbon and energy source through the non-phosphorylated Entner
      Doudoroff pathway. It has been suggested that this micro-organism metabolizes D
      gluconate, the oxidized form of D-glucose, to pyruvate and D-glyceraldehyde by
      using two unique enzymes, D-gluconate dehydratase and 2-keto-3-deoxy-D-gluconate
      aldolase. In the present study, we report the purification and characterization
      of D-gluconate dehydratase from S. solfataricus, which catalyses the conversion
      of D-gluconate into 2-keto-3-deoxy-D-gluconate. D-Gluconate dehydratase was
      purified 400-fold from extracts of S. solfataricus by ammonium sulphate
      fractionation and chromatography on DEAE-Sepharose, Q-Sepharose, phenyl-Sepharose
      and Mono Q. The native protein showed a molecular mass of 350 kDa by gel
      filtration, whereas SDS/PAGE analysis provided a molecular mass of 44 kDa,
      indicating that D-gluconate dehydratase is an octameric protein. The enzyme
      showed maximal activity at temperatures between 80 and 90 degrees C and pH values
      between 6.5 and 7.5, and a half-life of 40 min at 100 degrees C. Bivalent metal
      ions such as Co2+, Mg2+, Mn2+ and Ni2+ activated, whereas EDTA inhibited the
      enzyme. A metal analysis of the purified protein revealed the presence of one
      Co2+ ion per enzyme monomer. Of the 22 aldonic acids tested, only D-gluconate
      served as a substrate, with K(m)=0.45 mM and V(max)=0.15 unit/mg of enzyme. From
      N-terminal sequences of the purified enzyme, it was found that the gene product
      of SSO3198 in the S. solfataricus genome database corresponded to D-gluconate
      dehydratase (gnaD). We also found that the D-gluconate dehydratase of S.
      solfataricus is a phosphoprotein and that its catalytic activity is regulated by
      a phosphorylation-dephosphorylation mechanism. This is the first report on
      biochemical and genetic characterization of D-gluconate dehydratase involved in
      the non-phosphorylated Entner-Doudoroff pathway.

PMID- 15509195
TI  - Bacteria of preoperative urinary tract infections contaminate the surgical fields
      and develop surgical site infections in urological operations.
AB  - BACKGROUND: The risk factors for surgical site infection (SSI) following
      urological operations have not been clearly identified, although the presence of
      a preoperative urinary tract infection (UTI) is thought to be one risk factor. We
      studied potential risk factors to clarify when and how bacteria contaminate
      wounds and SSI develop. METHODS: Objects of the present study were patients with
      SSI after open urological operations that were performed at the Department of
      Urology, Miyazaki Medical College Hospital, University of Miyazaki, Kiyotake,
      Miyazaki, Japan, during the period between June 1999 and December 2000.
      Endourological operations, operations on children and short operations of less
      than 2 h duration were excluded. Patients were screened for the presence of UTI
      before the operation and subcutaneous swabs for culture were collected at the end
      of the operation by brushing with a sterile cotton-swab just before skin closure.
      RESULTS: Surgical site infections occurred in 20 of 134 patients. Bacteria from
      the subcutaneous swabs were detected in 15 (75.0%) of the patients with SSI. All
      patients received antimicrobial prophylaxis (AMP), but bacteria from the
      subcutaneous swabs of patients with SSI were less susceptible to the agents
      (20.0%). Preoperative UTI were observed in 11 (55.0%) of the patients with SSI.
      In these patients, four had the same species of bacteria detected from urine,
      swab and wound, three had the same species from swab and wound and one had the
      same species from urine and wound. CONCLUSIONS: Preoperative UTI was the most
      important risk factor for SSI following urological operations. It is most likely
      that the bacteria in the urine contaminated the surgical fields and the AMP
      resistant strains produced SSI.

PMID- 15509196
TI  - Inverse correlation of microvessel density with metastasis and prognosis in renal
      cell carcinoma.
AB  - BACKGROUND: Although a correlation between microvessel density (MVD) and tumor
      aggressiveness has been established for several malignancies, the data for renal
      cell carcinoma (RCC) is conflicting. In order to clarify the significance of MVD,
      we investigated the relationships between MVD and tumor stage, grade, size,
      occurrence of metastasis and patient survival. METHODS: Tumor specimens from 70
      patients with primary renal cell carcinoma were examined by immunohistochemical
      staining for CD34. RESULTS: There was a tendency for MVD to decrease from G1 to
      G3 tumors or from stage T1 to T3 tumors, although this was not statistically
      significant. However, the MVD for 56 non-metastatic and 14 metastatic tumors were
      significantly different (P = 0.005) at 109 +/- 67 and 58 +/- 35 per x400 field
      (mean +/- SD), respectively. Microvessel density for 36 large and 34 small tumors
      was also significantly different (P < 0.0001) at 48 +/- 22 and 142 +/- 54 per
      x400 field, respectively. The survival rate of patients with small, low grade and
      hypervascular tumors was significantly higher than that of patients with large (P
      = 0.0015), high grade (P = 0.05) or low MVD (P = 0.039) tumors. Cox proportional
      hazards regression analysis showed that tumor grade and size emerged as
      independent prognostic factors. CONCLUSION: High MVD in RCC was inversely
      associated with tumor aggressiveness, but MVD was not the independent prognostic
      factor.

PMID- 15509197
TI  - Estimation of damaged tubular epithelium in renal allografts by determination of
      vimentin expression.
AB  - BACKGROUND: Various invasive and non-invasive methods have been investigated for
      their prognostic value in predicting the outcome of renal allografts. In the
      present study, vimentin expression in tubular epithelial cells (TEC) was
      determined by the immunohistochemical examination of biopsy specimens and the
      prognostic value of this method was assessed. METHODS: Ninety-two renal
      transplant recipients were recruited for the present study. Protocol biopsy of
      the renal graft was performed 1, 3 and 5 years after transplantation in each
      case. All biopsy specimens were treated with conventional stains and
      immunostained with an antivimentin antibody. The correlation between vimentin
      expression and glomerular filtration rate (GFR) and the association between
      vimentin expression and histopathological findings were determined. RESULTS:
      Vimentin was localized in TEC adjacent to interstitial lesions with lymphocyte
      infiltration and also in TEC with tubulitis or in atrophic tubules. Vimentin
      positivity significantly correlated with GFR and both vimentin positivity and GFR
      were significantly associated with the extent of chronic allograft nephropathy,
      but not with acute rejection. Additionally, vimentin expression and GFR 3 and 5
      years after transplantation were higher in cases where graft loss occurred
      between 5 and 7 years after transplantation compared with graft survival cases.
      CONCLUSIONS: These results suggest that immunohistochemistry using antivimentin
      antibodies on protocol biopsy specimens is useful for the detection of injured
      TEC and as a predictor of allograft outcome.

PMID- 15509198
TI  - Mode of presentation and first line of management of non-recurrent urolithiasis
      in Kuwait.
AB  - AIMS: To determine the incidence, mode of presentation, first line of management
      and composition of non-recurrent urolithiasis in Kuwait. METHODS: Consecutive
      patients admitted between January 1999 and December 2002 with non-recurrent
      urolithiasis were prospectively analyzed. RESULTS: The average annual incidence
      of hospital admission for non-recurrent urolithiasis in Kuwait was 43.44 per
      100,000 population, representing men and women (ratio, 9:1) with a median age of
      41.91 years. Of the hospital admissions for non-recurrent urolithiasis, 57.2% of
      cases were acute. Overall, the most predominant symptom was flank pain, while the
      least common symptom was acute urinary retention. Ureteroscopic stone
      manipulation was the most common initial treatment modality in the present
      series, as it was utilized in 43.3% and 37.09% for patients admitted on elective
      and emergency basis, respectively. Of the calculi available for chemical
      analysis, 91% contained calcium, 73% contained calcium oxalate, 17% contained
      mixed calcium and 1% contained calcium phosphate. The composition of the rest of
      the stones were urate in 7%, struvite in 1% and cystine in 1%. CONCLUSIONS:
      Urolithiasis is a common disease in the Kuwait region that mainly presents with
      flank pain. Ureteroscopic calculus removal is the most common modality of
      treatment. The majority of the calculi seen in Kuwait contained calcium.

PMID- 15509199
TI  - Bladder cancer in Sri Lanka: experience from a tertiary referral center.
AB  - BACKGROUND: Bladder cancer is one of the most common malignancies occurring
      worldwide. No published data exists on bladder cancer in Sri Lanka. The objective
      of the study was to determine the clinicopathological characteristics of
      histologically confirmed transitional cell carcinoma (TCC) of the bladder in Sri
      Lanka. METHODS: Three hundred and one patients were diagnosed with primary
      bladder cancer during a 7.5-year period from 1993 to 2000. Two hundred and eighty
      one patients (239 men and 42 women; mean age, 66 years; range, 26-88) with TCC of
      the bladder were evaluated with regard to clinical presentation, cystoscopic
      findings and histopathological data. RESULTS: Transitional cell carcinoma
      accounted for 93.4% of primary bladder cancer. There was a male predominance with
      a sex ratio of 6:1. The majority of patients (63.7%) were in the 7th and 8th
      decades of life. Painless hematuria was the most common presenting symptom
      (52.7%), followed by painful hematuria (39.2%). The median duration of hematuria
      for all TCC patients, as well as for muscle-invasive TCC patients, was 3 months.
      Papillary configuration at cystoscopy, was found in 89.7% of non-invasive
      urothelial tumors. In contrast, 77.8% of invasive TCC patients had a solid/mixed
      tumor configuration. One hundred and forty-five patients (51.6% of TCC) had non
      invasive urothelial tumor and 136 patients (48.4%) had muscle-invasive disease.
      In the non-invasive urothelial tumor category, 61 patients (42.0%) had pTa tumors
      and 84 patients (58.0%) had pT1 tumors. Of newly diagnosed TCC cases, 5.3% were
      found to be T1G3 urothelial carcinomas. Fifty-six patients (38.6%) with non
      invasive urothelial tumor had a tumor greater than 5 cm in size. CONCLUSIONS:
      More than 90% of primary bladder tumors in Sri Lanka are TCC, with nearly half
      the patients having muscle-invasive diseases on initial presentation. Even in non
      invasive urothelial tumors, the majority (58.0%) have lamina propria invasion.

PMID- 15509200
TI  - Risk factors for febrile urinary tract infection in children with myelodysplasia
      treated by clean intermittent catheterization.
AB  - OBJECTIVE: To identify the factors involved in the incidence of febrile urinary
      tract infection (UTI) in a retrospective study of children with myelodysplasia
      who were treated by clean intermittent catheterization. METHODS: A total of 76
      myelodysplastic children were included in the present study. Any factors,
      including urodynamic parameters and urinary tract abnormalities, that may have
      been associated with the incidence of febrile UTI were evaluated using both a
      univariate analysis and a multiple logistic regression analysis. RESULTS: Of the
      76 patients, 19 (25%) had one or more episodes of febrile UTI. A univariate
      analysis showed low bladder compliance (<10 mL/cmH2O), detrusor overactivity,
      bladder trabeculation and the presence of vesico-ureteral reflux (VUR) to be
      significant factors in the incidence of febrile UTI. The presence of detrusor
      overactivity and a low bladder compliance, in addition to the presence of VUR,
      were found to be significant factors for the incidence of febrile UTI using a
      multivariate analysis. CONCLUSION: These results demonstrate that, in addition to
      VUR, urodynamics linked to bladder storage function disorder appear to be
      directly correlated with the cause of febrile UTI in children with
      myelodysplasia.

PMID- 15509202
TI  - Early catheter removal 3 days after radical retropubic prostatectomy.
AB  - AIM: We investigated the feasibility and safety of the early removal of urethral
      catheters 3 days after radical retropubic prostatectomy. METHODS: Seventy
      consecutive patients underwent radical retropubic prostatectomy with the intent
      of early catheter removal on postoperative day (POD) 3. Catheter removal was
      based on postoperative cystograms performed on POD 2. Patients were analyzed
      using a validated prostate cancer specific questionnaire (University of
      California, Los Angeles Prostate Cancer Symptom Index) to determine quality of
      life outcomes. Multiple logistic regression analysis was also used to evaluate if
      any of the preoperative or intraoperative parameters were able to predict the
      success of early catheter removal after radical retropubic prostatectomy.
      RESULTS: The catheter was removed on POD 3 in 67 of 70 patients (97%) excluding
      three patients with moderate or severe extravasation on postoperative cystograms.
      Of the 67 patients, 53 (76%) were successful in early catheter removal, but the
      remaining 14 (24%) patients experienced urinary retention within 48 h and were
      treated with simple catheter replacement for 1 or 2 days. Two patients developed
      anastomotic strictures 3 and 4 months postoperatively, which were managed by
      dilation alone. Multiple logistic regression analysis showed that no leak during
      an intraoperative leak test was the only independent predictor of success for
      early catheter removal (P = 0.0069; odds ratio, 6.667; 95% confidence interval,
      1.682-26.428). CONCLUSION: The present study revealed that early catheter removal
      3 days after radical retropubic prostatectomy is feasible in patients who show a
      negative intraoperative leak test. Postoperative monitoring of more patients is
      needed to determine if the early catheter removal is widely applicable.

PMID- 15509201
TI  - Interstitial laser coagulation for management of benign prostatic hyperplasia:
      long-term follow-up.
AB  - AIM: We evaluated the long-term results of transurethral interstitial laser
      coagulation in the treatment of benign prostatic hyperplasia (BPH) with up to 9
      years of follow up at the Kurashiki Central Hospital and determined the patient
      characteristics that predict a favorable outcome. METHODS: From December 1993 to
      May 1997, a total of 82 patients were enrolled in the present study. Subjective
      and objective voiding parameters were collected from medical records and a self
      administered questionnaire was sent to the patients. Kaplan-Meier plots were
      constructed to assess the risk of retreatment. RESULTS: The mean follow-up period
      was 48.4 months (range, 3-108 months). A total of 59 patients (72%) did not need
      any additional treatment at 12 months and 30 patients (37%) did not require
      additional treatment during the entire follow-up period. A total of 29 patients
      (35%) were retreated during follow-up. Transurethral prostate resection (TURP)
      was performed in 18 patients (22%). The remaining 11 patients (13%) were offered
      additional pharmacotherapy. The minimum and median retreatment-free durations
      were 3 and 14 months, respectively. Seven patients died and 17 were lost to
      follow-up. Men aged 71 years or older had greater likelihood of requiring
      retreatment than those younger than 71 years (P = 0.0397). No significant
      differences were noted in the other baseline characteristics. Among postoperative
      parameters, a rate of decrease of the International Prostate Symptom Score of the
      patient of lower than 60% and a rate of decrease in patient quality of life of
      lower than 50% at 3 months were associated with greater likelihood of retreatment
      (P = 0.0083 and P = 0.0006, respectively). CONCLUSIONS: Interstitial laser
      coagulation is effective for the treatment of BPH. Good long-term results and an
      acceptably low retreatment rate render this modality an effective alternative to
      TURP, especially for younger patients. Short-term improvement of subjective
      symptoms was predictive of favorable long-term outcome.

PMID- 15509203
TI  - Sublingual sildenafil in the treatment of erectile dysfunction: faster onset of
      action with less dose.
AB  - BACKGROUND: The aim of the present study was to show the efficacy and safety of
      sublingual sildenafil and to determine whether lower doses cause the same effect
      with a faster onset of action in this mode of application. METHODS: Forty
      consecutive patients with erectile dysfunction for more than three months were
      included in the study. The mean age was 55 years (range, 25-65). Serum glucose
      and testosterone levels, lipid profile and erectile function scores were obtained
      in all patients. Twenty patients received placebos and the other 20 patients
      received 20 mg sublingual sildenafil in a double blind randomized design.
      RESULTS: The effect of sildenafil on erection was significantly higher than that
      of placebo. Sixty-five percent of patients (13/20) who received sublingual
      sildenafil achieved satisfying erections and coitus, whereas the rate was 15% in
      the placebo group (3/20). The mean onset of action with sublingual sildenafil was
      15.5 min and lasted for an average of 40 min. Minimal headaches, sweating and
      flushing were noted as the side-effects. CONCLUSIONS: 20 mg sublingual sildenafil
      is safe and effective in the treatment of erectile dysfunction. Sublingual
      administration has some advantages as it is not effected by food ingestion and
      quickly appears in the circulation. These advantages provide a faster onset of
      action with a lower dose when compared to oral sildenafil. Sublingual use of
      sildenafil may be more cost-effective and possibly provides a more predictable
      onset of action.

PMID- 15509204
TI  - Biochemical modulation of 5-fluorouracil with interferon alpha/beta and gamma on
      murine renal cell carcinoma.
AB  - BACKGROUND: Conventional therapy for renal cell carcinoma (RCC) using interferon
      (IFN) has shown limited antitumor action. The purpose of the present study was to
      investigate the synergistic antitumor effects of IFN and 5-fluorouracil (5-FU)
      and to elucidate the mechanism underlying antitumor effects. METHODS: The
      antitumor effects and biochemical modulation of murine IFN and 5-FU were
      determined using murine renal cell carcinoma (RENCA). The activity of thymidylate
      synthase, thymidine kinase and the concentration of 5-FU incorporated into RNA
      was measured using cytosolic extracts of tumors. RESULTS: Triple combination
      therapy (5-FU, IFN alpha/beta and IFN gamma) showed a synergistic antitumor
      effect on RENCA tumors, because triple combination therapy suppressed growth
      significantly compared to combination therapy (IFN alpha/beta and IFN gamma, P =
      0.0258) and 5-FU (P < 0.0001). Total thymidylate synthase was decreased by triple
      combination therapy (5-FU, IFN alpha/beta and IFN gamma, P = 0.0019) and
      combination therapy (5-FU and IFN gamma, P = 0.0018) compared to 5-FU alone.
      Thymidine kinase activity was decreased by triple combination therapy (5-FU, IFN
      alpha/beta and IFN gamma, P < 0.0001) and combination therapy (5-FU and IFN
      alpha/beta, P < 0.0001) compared to 5-FU alone. The concentration of 5-FU
      incorporated into RENCA tumors was increased by triple combination therapy (P =
      0.0132) and combination therapy (5-FU and IFN alpha/beta, P = 0.0124) compared to
      5-FU alone. CONCLUSIONS: Interferons alpha/beta and gamma showed different
      biochemical modulation for 5-FU. Therefore, combination therapy using 5-FU and
      IFN showed synergistic antitumor effects on murine RCC.

PMID- 15509205
TI  - Electroporation-mediated muscarinic M3 receptor gene transfer into rat urinary
      bladder.
AB  - BACKGROUND: Muscarinic M3 (M3) receptor has been recognized as a major muscarinic
      receptor for smooth muscle contractions of the urinary bladder. Under the
      hypothesis that overexpression of M3 receptor in the urinary bladder would
      enhance urinary bladder contractions, we have transferred the M3 receptor gene
      into rat bladders using electroporation (EP) and evaluated the functional
      expression of the transferred gene. METHODS: Plasmids expressing luciferase, a
      green fluorescence protein and M3 receptor were injected into the rat bladder and
      square-wave electric pulses were immediately applied. Two days after gene
      transfer, we analyzed gene expression. Immunohistochemical staining was performed
      and the contractile responses from isolated bladder strips, which were induced
      KCl, carbachol and electrical field stimulation (EFS), were evaluated. RESULTS:
      The optimal conditions of electroporation were 8 pulses, 45 voltages, 50
      milliseconds/pulses and 1 Hz. Under these conditions, luciferase gene expression
      was enhanced approximately 300-fold, compared to an injection of DNA only.
      Regarding immunohistochemistry with an anti-M3 receptor, an increase in
      immunoactivity was observed in the M3 receptor gene transferred rat bladder,
      compared to the bladder of the control rat. In rats with the transferred M3
      receptor gene, carbachol- and EFS-induced maximum contractile responses of
      bladder smooth muscle strips significantly increased. CONCLUSIONS: These findings
      suggest that an in vivo EP procedure is an useful method for gene transfer into
      the bladder and that an overexpression of M3 receptor in the rat bladder enhances
      bladder contractility. This technique may become a new treatment modality for
      detrusor underactivity.

PMID- 15509206
TI  - Global analysis of gene expression profiles in ileum in a rat bladder
      augmentation model using cDNA microarrays.
AB  - BACKGROUND: The objective of the present study was to globally characterize the
      changes in the gene expression profile in the ileum after long-term urine
      exposure in a rat ileal augmented bladder model using cDNA microarrays. METHODS:
      Bladder augmentation using the ileum was performed in female 8-week-old rats. The
      ileal epithelia used for bladder augmentation were harvested 1 and 3 months
      postoperatively and changes in the gene expression in these tissues were compared
      with that of intact ileal epithelia from sham-operated rats using cDNA
      microarrays consisting of 1176 rat genes. RESULTS: Marked changes in gene
      expression in the ileum used for bladder augmentation were observed for 30 genes
      (16 up-regulated and 14 down-regulated genes). The differentially expressed genes
      include those associated with signal transduction, cell adhesion and stress
      response. Subsequent evaluation of changes in two randomly selected genes from
      the 30 differentially expressed genes by semiquantitative reverse transcription
      polymerase chain reaction demonstrated the reliability of the present cDNA
      microarray analyses. CONCLUSION: The present experiments identified an extensive
      list of genes differentially expressed in the ileum after bladder augmentation,
      providing valuable information for the pathophysiological assessment of patients
      who undergo urinary reconstruction and representing a source of novel targets for
      treating complications after urinary diversion.

PMID- 15509207
TI  - Spontaneous rupture of adrenal pheochromocytoma with capsular invasion.
AB  - A 67-year-old Japanese man developed a sudden onset of severe right-side upper
      abdominal pain, nausea and vomiting. On hospitalization, physical examination
      revealed sweating, tachycardia, hypertension and the appearance of peripheral
      vasoconstriction. An urgent computed tomography scan with contrast demonstrated a
      large hematoma in the right retroperitoneal space. A phentolamine test and an
      131iodine metaiodobenzylguanidine scan suggested pheochromocytoma. An elective
      right adrenalectomy was successfully performed after pretreatment for sufficient
      volume replacement with continuous administration of alpha- and beta-adrenergic
      blocking agents. Pathological diagnosis was an adrenal pheochromocytoma 9.0 x 6.5
      cm in diameter with evidence of capsular invasion, which could be associated with
      a tear in the capsule.

PMID- 15509209
TI  - Laparoscopic partial nephrectomy for a renal tumor with tumor-feeding artery
      ligation: left renal cell carcinoma in the posterior mid zone.
AB  - The most serious problem regarding a laparoscopic partial nephrectomy is how to
      perform bloodless excision without causing renal ischemia in a limited working
      space. We report the case of a 65-year-old man with left small renal cell
      carcinoma in the posterior mid zone who underwent a laparoscopic partial
      nephrectomy through a retroperitoneal approach by carrying out the ligation of
      the tumor-feeding artery, but without clamping the renal pedicle. Both
      preoperative abdominal computed tomography (CT) and intraoperative
      ultrasonography revealed the tumor to be fully encapsulated. The tumor-feeding
      artery could be exposed by dissection from the renal hilum and, after an arterial
      ligation, tumor resection with a safety margin was smoothly performed with
      minimal bleeding. Postoperatively, CT revealed a limited defect of the renal
      parenchyma and excretory pyelography showed no urine leakage or urinary tract
      obstruction. The preoperative and postoperative creatinine levels were 0.66 and
      0.69 mg/dL, respectively. As a result, a tumor-feeding artery ligation with a
      laparoscopic partial nephrectomy for left renal cell carcinoma in the posterior
      mid zone is considered to be an effective surgical modality which avoids renal
      ischemia and pelvic heat injury.

PMID- 15509208
TI  - Mucinous adenocarcinoma of the renal pelvis associated with transitional cell
      carcinoma in the renal pelvis and the bladder.
AB  - We report a case of mucinous adenocarcinoma of the renal pelvis associated with
      bladder carcinoma in situ (CIS). Transitional cell carcinoma (TCC) of the renal
      pelvis and CIS were also observed adjacent to the adenocarcinoma.
      Immunohistochemical assessment of the pelvic adenocarcinoma revealed positive
      expressions for mucin, epithelial membrane antigen, cytokeratin 7, cytokeratin 19
      and carcinoembryonal antigen, but not vimentin or chromogranin. Based on the
      histopathological examinations, the adenocarcinoma of the renal pelvis in the
      present case may have a similar biological nature to conventional TCC and
      probably originated by development of pre-existing TCC of the renal pelvis.

PMID- 15509210
TI  - Ureteral obstruction due to retroperitoneal fibrosis secondary to a solitary
      internal iliac aneurysm.
AB  - We report a case of ureteral obstruction due to retroperitoneal fibrosis
      secondary to a solitary left internal iliac aneurysm. It has been reported that
      as a cause of ureteral obstruction, an internal iliac aneurysm without aortic
      and/or common iliac aneurysms is very rare. In the present case, magnetic
      resonance imaging was a useful modality to diagnose retroperitoneal fibrosis
      secondary to an internal iliac aneurysm as a direct cause of ureteral
      obstruction.

PMID- 15509211
TI  - Intravesical mass consisting of mucosa-associated lymphoid tissue.
AB  - We report on a patient with an intravesical mass consisting of hyperplastic
      follicles in mucosa-associated lymphoid tissue. Computed tomography and
      ultrasonography revealed two intravesical masses measuring 3.5 cm and 1.5 cm
      along the long axis. Imaging diagnosis was invasive tumors of the bladder.
      However, the pathological diagnosis on transurethral bladder tumor biopsy was a
      lesion in lamina propria consisting of hyperplastic follicles and lymphatic
      infiltrate between them with no cell atypia. Light microscopically, the lesion
      was considered to be reactive follicular hyperplasia. Antibiotic therapy resulted
      in an almost complete disappearance of the tumors. Such large follicular
      hyperplasia in the lamina propria of the bladder is rare.

PMID- 15509212
TI  - Twenty-three years of disease-free survival following cutaneous metastasis from a
      primary bladder transitional cell carcinoma.
AB  - We present a case of cutaneous metastases from a primary bladder transitional
      cell carcinoma (TCC), with a prolonged survival of 23 years. Cutaneous metastases
      from primary bladder TCC are uncommon and, like all metastases, have a poor
      prognosis. The common modality of treatment of cutaneous metastases from a
      primary bladder cancer is wide local excision of the metastases followed by
      combination chemotherapy. Here, we present a case of a solitary cutaneous
      metastasis from a primary bladder TCC, which was treated with wide local excision
      and single agent chemotherapy. Twenty-three years on, the patient remains disease
      and recurrence free.

PMID- 15509213
TI  - Large intestinal type-urachal adenocarcinoma with focal expression of prostatic
      specific antigen.
AB  - We present a case of colonic-type adenocarcinoma, which might arise from an
      urachal remnant through a villous adenoma. The cancer tissue in the present case
      showed focal immunoreaction to prostate-specific antigen (PSA). This is the first
      report of urachal adenocarcinoma expressing PSA.

PMID- 15509214
TI  - Papillary cystadenocarcinoma of the prostate.
AB  - A giant cystic formation was found behind the prostate of a 69-year-old man who
      presented with urinary retention. Ultrasonography, computed tomography scans and
      magnetic resonance imaging revealed a large cystic intrapelvic mass and biopsy of
      the cyst wall diagnosed papillary cyst adenocarcinoma. Immunohistochemically, the
      tumor originated from the prostate.

PMID- 15509215
TI  - Inguinal hernia of seminal vesicle cyst.
AB  - Seminal vesicle cysts are uncommon abnormalities in the pelvis. The case of a
      seminal vesicle cyst that extended through the inguinal canal is reported. A 35
      year-old man presented with left inguinal swelling. He was diagnosed with a left
      inguinal hernia. However, the interpretative diagnosis was a spermatic cord
      tumor. The operation was changed to tumor resection. The tumor existed along with
      the vas deferens from part of the parietal peritoneum outside the inguinal tunnel
      to the deep pelvic space. The cylinder-shaped tumor was 3 cm in diameter and 20
      cm long. Pathological examination revealed a seminal vesicle cyst that extended
      through the inguinal canal. To the best of our knowledge, this is the first case
      report of a seminal vesicle cyst inguinal hernia.

PMID- 15509216
TI  - Primary carcinoid tumor of the bilateral testis associated with carcinoid
      syndrome.
AB  - Carcinoid tumors derived from neuroendocrine cells can release serotonin and
      other vasoactive substances into the systemic circulation, resulting in carcinoid
      syndrome. Testicular carcinoid, a rare disease accounting for less than 1% of all
      testicular neoplasms, rarely manifests symptoms of carcinoid syndrome. We
      describe a case of carcinoid syndrome arising from a primary testicular carcinoid
      tumor. A 21-year-old male patient presented with facial flushing and diarrhea for
      5 years. He had an enlarged left testis and a 1-cm, ill-defined, hard, non-tender
      mass in his right testis. His 24 h urinary excretion of 5-hydroxyindoleacetic
      acid was elevated (16.1 mg/day). Somatostatin receptor scintigraphy correlated
      with carcinoid tumor in both testes. Following bilateral orchiectomy, the
      patient's facial flushing and diarrhea disappeared.

PMID- 15509217
TI  - Late relapse of stage I testicular seminoma metastatic to just a para
      ureteropelvic region.
AB  - A follow-up ultrasonography study 43 months after an operation for left stage I
      testicular seminoma in a 39-year-old man revealed left hydronephrosis. Serum beta
      human chorionic gonadotropin (beta-hCG) levels were slightly increased. Computed
      tomography scans of the abdomen showed a bulky tumor around the ureteropelvic
      region without para-aortic lymph node enlargement, but did not show a clear
      distinction between a recurrence of the testicular tumor and an invasive ureteral
      tumor. After the patient underwent two cycles of chemotherapy with cisplatin and
      etoposide, the tumor mass decreased by approximately 60% and beta-hCG levels
      returned to normal. We then performed a resection of the residual tumor involving
      the upper ureter and left kidney and a retroperitoneal lymph node dissection
      under a clinical diagnosis of recurrence of the testicular tumor. Histologically,
      no viable cancer cells remained. The patient has been well with no evidence of
      recurrence for more than two years.

PMID- 15509218
TI  - Transsphincteric repair of rectourethral fistulas following laparoscopic radical
      prostatectomy.
AB  - Rectourethral fistula is a serious complication following laparoscopic radical
      prostatectomy. We report our experience with a transsphincteric approach in the
      repair of this uncommon complication. The rectourethral fistula was repaired in a
      three-stage procedure comprising fecal diversion, transsphincteric repair of the
      fistula and, finally, closure of the stoma. Two patients with rectourethral
      fistulas underwent this procedure and the postoperative course was uneventful. In
      conclusion, a transsphincteric approach in the repair of rectourethral fistula by
      a three-stage procedure is safe and may be the treatment of choice.

PMID- 15509219
TI  - Hair cells in ascidians and the evolution of lateral line placodes.

PMID- 15509220
TI  - Thyroid hormones determine developmental mode in sand dollars (Echinodermata:
      Echinoidea).
AB  - Evolutionary transitions in larval nutritional mode have occurred on numerous
      occasions independently in many marine invertebrate phyla. Although the
      evolutionary transition from feeding to nonfeeding development has received
      considerable attention through both experimental and theoretical studies,
      mechanisms underlying the change in life history remain poorly understood.
      Facultative feeding larvae (larvae that can feed but will complete metamorphosis
      without food) presumably represent an intermediate developmental mode between
      obligate feeding and nonfeeding. Here we show that an obligatorily feeding larva
      can be transformed into a facultative feeding larva when exposed to the thyroid
      hormone thyroxine. We report that larvae of the subtropical sand dollar Leodia
      sexiesperforata (Echinodermata: Echinoidea) completed metamorphosis without
      exogenous food when treated with thyroxine, whereas the starved controls (no
      thyroxine added) did not. Leodia sexiesperforata juveniles from the thyroxine
      treatment were viable after metamorphosis but were significantly smaller and
      contained less energy than sibling juveniles reared with exogenous food. In a
      second starvation experiment, using an L. sexiesperforata female whose eggs were
      substantially larger than in the first experiment (202+/-5 vs. 187+/-5 microm), a
      small percentage of starved L. sexiesperforata larvae completed metamorphosis in
      the absence of food. Still, thyroxine-treated larvae in this experiment completed
      metamorphosis faster and in much higher numbers than in the starved controls.
      Furthermore, starved larvae of the sand dollar Mellita tenuis, which developed
      from much smaller eggs (100+/-2 microm), did not complete metamorphosis either
      with or without excess thyroxine. Based on these data, and from recent
      experiments with other echinoids, we hypothesize that thyroxine plays a major
      role in echinoderm metamorphosis and the evolution of life history transitions in
      this group. We discuss our results in the context of current life history models
      for marine invertebrates, emphasizing the role of egg size, juvenile size, and
      endogenous hormone production for the evolution of nonfeeding larval development.

PMID- 15509222
TI  - Patterning of the branched head appendages in Schistocerca americana and
      Tribolium castaneum.
AB  - Much of our understanding of arthropod limb development comes from studies on the
      leg imaginal disc of Drosophila melanogaster. The fly limb is a relatively simple
      unbranched (uniramous) structure extending out from the body wall. The molecular
      basis for this outgrowth involves the overlap of two signaling molecules,
      Decapentaplegic (Dpp) and Wingless (Wg), to create a single domain of distal
      outgrowth, clearly depicted by the expression of the Distal-less gene (Dll). The
      expression of wg and dpp during the development of other arthropod thoracic limbs
      indicates that these pathways might be conserved across arthropods for uniramous
      limb development. The appendages of crustaceans and the gnathal appendages of
      insects, however, exhibit a diverse array of morphologies, ranging from those
      with no distal elements, such as the mandible, to appendages with multiple distal
      elements. Examples of the latter group include branched appendages or those that
      possess multiple lobes; such complex morphologies are seen for many crustacean
      limbs as well as the maxillary and labial appendages of many insects. It is
      unclear how, if at all, the known patterning genes for making a uniramous limb
      might be deployed to generate these diverse appendage forms. Experiments in
      Drosophila have shown that by forcing ectopic overlaps of Wg and Dpp signaling it
      is possible to generate artificially branched legs. To test whether naturally
      branched appendages form in a similar manner, we detailed the expression patterns
      of wg, dpp, and Dll in the development of the branched gnathal appendages of the
      grasshopper, Schistocerca americana, and the flour beetle, Tribolium castaneum.
      We find that the branches of the gnathal appendages are not specified through the
      redeployment of the Wg-Dpp system for distal outgrowth, but our comparative
      studies do suggest a role for Dpp in forming furrows between tissues.

PMID- 15509221
TI  - Expression patterns of the rogue Hox genes Hox3/zen and fushi tarazu in the
      apterygote insect Thermobia domestica.
AB  - Many embryonic patterning genes are remarkably conserved between vertebrates and
      invertebrates, and the Hox genes are paradigmatic examples of this conservation.
      Yet even Hox genes can change dramatically in evolution. Two genes in particular-
      Hox3 and fushi tarazu--lost their ancestral roles as homeotic genes and play very
      different developmental roles in the fruit fly Drosophila melanogaster. The
      Drosophila Hox3 homologs zerknullt and bicoid act in extraembryonic tissues and
      in establishment of the anteroposterior axis, respectively, whereas fushi tarazu
      acts in segmentation and neurogenesis. It would be valuable to know what
      mechanisms allowed Hox3 and ftz to abandon their ancestral roles as homeotic
      genes and take on new roles. To explore the evolutionary transition of these
      genes, we analyzed their expression in a primitive insect, the firebrat Thermobia
      domestica. The expression patterns seem to represent a stage of evolution
      intermediate between the ancestral state seen in basal arthropods and the derived
      expression patterns in Drosophila. These expression data help us to narrow the
      period in which the gene transitions took place. Hox3 appears to have evolved
      directly into zen within the insects, whereas ftz seems to have adopted the
      expression patterns of a segmentation and neurogenesis gene earlier in the
      mandibulate arthropods.

PMID- 15509223
TI  - Conservation and divergence of BMP2/4 genes in the lamprey: expression and
      phylogenetic analysis suggest a single ancestral vertebrate gene.
AB  - Bone morphogenetic protein (BMP) molecules are members of a large family of
      signaling molecules important in numerous developmental pathways throughout the
      metazoa. Single members of the BMP2/4 class have been found in invertebrates such
      as cnidarians, arthropods, nematodes, echinoderms, ascidians, and
      cephalochordates. In all vertebrates studied, there are at least two copies, BMP2
      and BMP4, that play important roles in axial patterning, tissue specification,
      and organogenesis. The basal vertebrate, lamprey, diverged near the time of
      vertebrate origins and is useful for understanding the gene duplication events
      that led to the increased complexity of the vertebrate genome. We characterized
      the sequence and expression pattern of BMP2/4 class genes in the sea lamprey,
      Petromyzon marinus. We uncovered three genes that we named PmBMP2/4A, PmBMP2/4B,
      and PmBMP2/4C. Phylogenetic analysis indicates that PmBMP2/4A is closer than
      PmBMP2/4B or PmBMP2/4C in sequence identity to both BMP2 and BMP4 of
      gnathostomes. The developmental expression pattern of PmBMP2/4A also more closely
      resembles the combined early expression patterns of gnathostome BMP2 and BMP4,
      whereas PmBMP2/4B and PmBMP2/4C appear to play roles only later in development.
      Cell labeling showed that the BMP-expressing cells in the branchial arches of
      lampreys are of neural crest origin. Taken together, our sequence and expression
      data support the duplication of BMP2/4 genes in the lamprey from a single
      ancestral vertebrate BMP2/4 gene.

PMID- 15509224
TI  - Conserved expression domains for genes upstream and within the HoxA and HoxD
      clusters suggests a long-range enhancer existed before cluster duplication.
AB  - The posterior HoxA and HoxD genes are essential in appendicular development.
      Studies have demonstrated that a "distal limb enhancer," remotely located
      upstream of the HoxD complex, is required to drive embryonic autopod expression
      of the posterior Hox genes as well as the two additional non-Hox genes in the
      region: Evx2 and Lnp. Our work demonstrates a similar mode of regulation for
      Hoxa13 and four upstream genes: Evx1, Hibadh, Tax1bp, and Jaz1. These genes all
      show embryonic (E11.5-E13.5) distal limb and genital bud expression, suggesting
      the existence of a nearby enhancer influencing the expression of a domain of
      genes. Comparative sequence analysis between homologous human and mouse genomic
      sequence upstream of Hoxa13 revealed a remote 2.25-kb conserved noncoding
      sequence (mmA13CNS) within the fourth intron of the Hibadh gene. mmA13CNS shares
      a common 131-bp core identity within a conserved noncoding sequence upstream of
      Hoxd13, which is located within the previously identified distal limb enhancer
      critical region. To test the function of this conserved sequence, we created
      mmA13CNS-Hsp86-lacZ transgenic mice. mmA13CNS directed a wide range of tissue
      expression, including the central nervous system, developing olfactory tissue,
      limb, and genital bud. Limb and genital bud expression directed by mmA13CNS is
      not identical to the patterns exhibited by Hoxa13/Evx1/Hibadh/Tax1bp1/Jaz1,
      suggesting that mmA13CNS is not sufficient to fully recapitulate their expression
      in those tissues. The Evx1- and Evx2-like central nervous system expression
      observed in these mice suggests that the long-range regulatory element(s) for the
      Hox cluster existed before the cluster duplication.

PMID- 15509225
TI  - Kin or self-recognition? Colonial fusibility of the bryozoan Celleporella
      hyalina.
AB  - We estimated fusion frequency with respect to coancestry in the bryozoan
      Celleporella hyalina, whose briefly planktonic sexually produced larvae settle on
      algal substrata and proceed to form encrusting colonies by iterative budding.
      Frequency of fusion between paired colonies growing on an artificial substratum
      was positively correlated with coefficient of relatedness, with allorecognition
      ability increasing during the early stages of colonial growth after larval
      settlement. Parents repressed the growth of F1 progeny with which they had fused.
      The results are concordant with the Feldgarden-Yund model of selection for self
      recognition, which regards fusion with kin as an inevitable source of error whose
      cost diminishes with increasing relatedness. Contrary to fusion compatibility,
      gametic compatibility is negatively correlated with coancestry, indicating a need
      for further research on the possibility of common or linked genetic control that
      has opposite effect at somatic and gametic levels.

PMID- 15509226
TI  - Investigating the independent evolution of the size of floral organs via G-matrix
      estimation and artificial selection.
AB  - The attractiveness of a plant to pollinators is dependent on both the number of
      flowers produced and the size of the petals. However, limiting resources often
      result in a size/number trade-off, whereby the plant can make either more flowers
      or larger flowers, but not both. If developmental genes underlying sepal and
      petal identity (some of which overlap) also influence size, then this shared
      genetic basis could constrain the independent evolution of floral size and
      attractiveness. Here, we determined whether the size of sepals and petals in the
      dioecious perennial, Silene latifolia, are developmentally independent by
      performing two experiments: a genetic variance-covariance experiment to estimate
      genetic correlations between calyx width, petal-limb length, flower mass, and
      number and a four-bout artificial-selection experiment to alter calyx width and
      estimate the correlated response in petal-limb length. In addition, we determined
      whether variation in petal-limb length is the result of cell expansion or cell
      proliferation. The first experiment revealed that petal-limb length is not
      genetically correlated with calyx width, and the second experiment confirmed
      this; selection on calyx width did not result in a predictable or significant
      change in petal-limb length. Flower number was negatively correlated with all the
      floral traits measured, indicating a flower size/number trade-off. Cell number,
      but not size, explained a significant amount of the variation in petal-limb
      length. We conclude that the size of the two outer floral organs can evolve
      independently. This species can therefore increase the number of flowers produced
      by decreasing investment in the calyx without simultaneously decreasing petal
      size and the attractiveness of each individual flower to pollinators.

PMID- 15509227
TI  - APETALA3 and PISTILLATA homologs exhibit novel expression patterns in the unique
      perianth of Aristolochia (Aristolochiaceae).
AB  - Several lines of evidence suggest that sterile floral organs, collectively known
      as the perianth, have evolved multiple times during the evolution of the
      angiosperms. In the family Aristolochiaceae, the perianth is formed by two whorls
      of organs in the genus Saruma but by only one whorl in the remaining genera,
      including Aristolochia. Although the morphology of Saruma is similar in
      appearance to the core eudicot perianth, with leaf-like sepals and showy colored
      petals, the unipartite perianth of Aristolochia combines morphological aspects of
      both calyx and corolla. To investigate the organ identity program functioning in
      the novel perianth of Aristolochia, we identified homologs of the B-class genes
      APETALA3 (AP3) and PISTILLATA (PI) in both Saruma and Aristolochia. The
      expression patterns of these genes in Saruma indicate they are functioning in the
      development of the second whorl petaloid organs and third whorl stamens. In
      Aristolochia, however, the expression of AP3 and PI homologs in the perianth does
      not suggest a role in organ identity but, rather, in promoting late aspects of
      cell differentiation. The implications of these findings for the evolution of
      both petaloidy and B gene function are discussed.

PMID- 15509230
TI  - Synergism between topiramate and budipine in refractory status epilepticus in the
      rat.
AB  - PURPOSE: To evaluate the antiepileptic and neuroprotective properties of
      topiramate (TPM) alone and with coadministration of the N-methyl-D-aspartate
      (NMDA)-receptor antagonist budipine in a rat model of refractory status
      epilepticus. METHODS: Male Sprague-Dawley rats had electrodes implanted into the
      perforant path and dentate granule cell layer of the hippocampus under halothane
      anesthesia. Approximately 1 week after surgery, the perforant path of each animal
      was electrically stimulated for 2 h to induce self-sustaining status epilepticus.
      Successfully stimulated rats were given intraperitoneally vehicle (n = 6), TPM
      (20-320 mg/kg; n = 28), budipine (10 mg/kg; n = 5), or budipine (10 mg/kg) and
      TPM (80 mg/kg; n = 6) 10 min after the end of the stimulation and monitored
      behaviorally and electroencephalographically for a further 3 h. The animals were
      killed 14 days later, and histopathology was assessed. RESULTS: Neither budipine
      alone nor TPM at any dose terminated status epilepticus. Despite this, TPM
      resulted in various degrees of neuroprotection at doses between 40 and 320 mg/kg.
      Coadministration of budipine with TPM terminated the status epilepticus in all
      rats. This combination also significantly improved the behavioral profile and
      prevented status-induced cell death compared with control. CONCLUSIONS: Budipine
      and TPM are an effective drug combination in stopping self-sustained status
      epilepticus, and TPM alone was neuroprotective, despite the continuation of
      seizure activity.

PMID- 15509231
TI  - Lasting secondary antiepileptogenesis induced by cingulate kindling.
AB  - PURPOSE: To test the validity of a hypothesis that kindling-induced enduring
      kindling inhibition of the homotopic secondary site is not a primate species
      specific effect but occurs also in feline species. METHODS: Five mature male cats
      were kindled at the anterior (AC) and posterior (PC) cingulate cortex followed by
      secondary-site kindling and primary-site retest. RESULTS: Kindling was
      characterized by a marked seizure-stage instability and a progressive
      afterdischarge threshold elevation in all the animals. A protracted nonconvulsive
      seizure stage was followed by convulsive evolution and rapid generalization. At
      the secondary site, positive transfer effect was absent, and kindling did not
      occur. Primary-site retest activated kindled seizure within three stimulations.
      Recurrent spontaneous seizures, identical to the primary-site kindled seizure,
      occurred in two AC-kindled animals. Subsequent to this, a markedly elevated
      afterdischarge threshold also was found at some distant cortical and subcortical
      sites, to which the afterdischarge propagated. Kindling of the amygdala
      ipsilateral to the kindled AC or PC was tardy, with no positive transfer effect.
      However, it was associated with afterdischage threshold reduction. CONCLUSIONS:
      Cingulate kindling-induced enduring kindling inhibition at a homotopic secondary
      site is not a primate species-specific effect and occurs also in feline species.
      It is not limited to a homotopic site and represents a lasting secondary
      antiepileptogenesis, presumably due to enhanced intrinsic inhibitory mechanism(s)
      available to the mammalian brain. A selective afterdischarge threshold elevation
      concurrently observed is suspected to be a feline species-specific effect.

PMID- 15509232
TI  - Lipopolysaccharide-induced febrile convulsions in the rat: short-term sequelae.
AB  - PURPOSE: Febrile convulsions (FCs) occur in children as a result of fever. The
      mechanisms involved in the genesis of FCs and their long-term consequences on
      brain development remain unclear. We have developed a model of FC, by using fever
      as a parameter, to test the hypothesis that fever can lower seizure threshold and
      to examine the neurologic sequelae of FCs. METHODS: Fourteen-day-old rat pups
      equipped with body-temperature telemetry devices exhibited approximately 1.5
      degrees C fevers after lipopolysaccharide (Escherichia coli, 200 microg/kg).
      During such fevers, concurrently administered doses of kainic acid that are
      normally subconvulsant were used to induce convulsions with fever. Animals were
      then killed at varying times for pathological and immunohistochemical studies.
      RESULTS: The pairing of lipopolysaccharide and subconvulsant kainic acid resulted
      in convulsions in approximately 50% of febrile animals, with very low mortality.
      To study the neural correlates of these FCs, we used fos immunohistochemistry and
      found that animals with FCs had fos-positive immunoreactivity in brain regions
      involved in seizures. After a period of 72 h, we also examined brains for
      pathologic changes and found no differences among our groups. CONCLUSIONS: Our
      data indicate that a neuroimmune challenge and its accompanying fever reduce the
      seizure threshold. Furthermore, the FCs induced by fever in this model do not
      have short-term adverse effects on the brain. In addition, this model, by
      incorporating physiologic fever, may be useful for examining the role of fever
      and its constituent mediators in the genesis of FCs.

PMID- 15509233
TI  - Fracture risk associated with use of antiepileptic drugs.
AB  - PURPOSE: To assess fracture risk associated with different antiepileptic drugs
      (AEDs). An increased fracture risk has been reported in patients with epilepsy.
      Classical AEDs have been associated with decreased bone mineral density. The
      effects of newer AEDs are unknown. METHODS: We undertook a population-based
      pharmacoepidemiologic case-control study with any fracture as outcome and use of
      AEDs as exposure variables (124,655 fracture cases and 373,962 controls).
      RESULTS: All AEDs were associated with an increased fracture risk in an
      unadjusted analysis. After adjustment for prior fracture, use (ever) of
      corticosteroids, comorbidity, social variables, and diagnosis of epilepsy,
      carbamazepine [CBZ; odds ratio (OR), 1.18; 95% confidence interval (CI), 1.10
      1.26], [and oxcarbazepine (OXC; 1.14, 1.03-1.26)], clonazepam (CZP; 1.27, 1.15
      1.41), phenobarbital (PB; 1.79, 1.64-1.95), and valproate (VPA; 1.15, 1.05-1.26)
      were statistically significantly associated with risk of any fracture.
      Ethosuximide (0.75, 0.37-1.52), lamotrigine (1.04, 0.91-1.19), phenytoin (1.20,
      1.00-1.43), primidone (1.18, 0.95-1.48), tiagabine (0.75, 0.40-1.41), topiramate
      (1.39, 0.99-1.96), and vigabatrin (0.93, 0.70-1.22) were not statistically
      significantly associated with fracture risk after adjustment for confounders. The
      relative increase was modest and in the same range for the significant and
      nonsignificant results. CBZ, PB, OXC, and VPA displayed a dose-response relation.
      Fracture risk was more increased by liver-inducing AEDs (OR, 1.38; 95% CI, 1.31
      1.45) than by noninducing AEDs (1.19; 95% CI, 1.11-1.27). CONCLUSIONS: A very
      limited increased fracture risk is present in users of CBZ, CZP, OXC, PB, and
      VPA. A limited significant increase cannot be excluded for the other AEDs because
      of the statistical power.

PMID- 15509234
TI  - Could valerian have been the first anticonvulsant?
AB  - PURPOSE: To assess the available evidence for the belief that valerian, highly
      recommended in the past for treating epilepsy, possessed real anticonvulsant
      effectiveness. METHODS: Review of available literature. RESULTS: In 1592, Fabio
      Colonna, in his botanical classic Phytobasanos, reported that taking powdered
      valerian root cured his own epilepsy. Subsequent reports of valerian's
      anticonvulsant effectiveness appeared. By the late 18th and early 19th centuries,
      it was often regarded as the best available treatment for the disorder. Valerian
      preparations yield isovaleric acid, a substance analogous to valproic acid and
      likely to possess anticonvulsant properties, as isovaleramide does. In favorable
      circumstances, high valerian doses can be calculated to have sometimes provided
      potentially effective amounts of anticonvulsant substance for epilepsy patients.
      CONCLUSIONS: Valerian probably did possess the potential for an anticonvulsant
      effect, but the uncertain chemical composition and content of valerian
      preparations, and their odor and taste, made it unlikely that they could ever
      prove satisfactory in widespread use.

PMID- 15509235
TI  - "Convulsive" nonepileptic seizures have a characteristic pattern of rhythmic
      artifact distinguishing them from convulsive epileptic seizures.
AB  - PURPOSE: Approximately 30% of patients admitted for video-EEG monitoring have
      psychogenic nonepileptic seizures (PNES). Differentiation of "convulsive" PNES
      from convulsive seizures can be difficult. The EEG often displays rhythmic
      movement artifact that may resemble seizure activity and confound the
      interpretation. We sought to determine whether time-frequency mapping of the
      rhythmic EEG artifact during "convulsive" PNES reveals a pattern that differs
      from that of epileptic seizures. METHODS: EEGs from 15 consecutive patients with
      "convulsive" PNESs were studied with time-frequency mapping by using NEUROSCAN
      and compared with 15 patients with convulsive epileptic seizures. Fast Fourier
      transforms (FFTs) were performed to determine the dominant frequency for 1- to 2
      s windows every 2 s through the seizures. RESULTS: The dominant frequency
      remained stable within a narrow range for the duration of the PNES, whereas in
      the epileptic seizures, it evolved through a wide range. The coefficient of
      variation of the frequency during the seizures was considerably less for patients
      without epilepsy (median, 15.0%; range, 7.2-23.7% vs. median, 58.0%; range, 34.8
      92.1%; p < 0.001). The median frequency did not differ significantly between
      groups (4.2 vs. 4.6 Hz; p = 0.290). CONCLUSIONS: "Convulsive" PNES display a
      characteristic pattern on time-frequency mapping of the EEG artifact, with a
      stable, nonevolving frequency that is different from the evolving pattern seen
      during an epileptic seizure.

PMID- 15509236
TI  - Interictal temporal delta activity in temporal lobe epilepsy: correlations with
      pathology and outcome.
AB  - PURPOSE: To determine the characteristics and the clinical significance of focal
      slow activity and its association with focal epileptogenesis in patients with
      temporal lobe epilepsy (TLE). METHODS: We analyzed the interictal EEGs of 141
      patients who had temporal lobe resections for intractable focal seizures and
      correlated the findings with pathologic changes and outcome. The pathologic
      changes were categorized into medial temporal sclerosis, tumors, and nonspecific
      changes. RESULTS: Lateralized slow activity was found in 66% of the patients, and
      it was mainly temporal, of delta frequency and irregular morphology. None of its
      characteristics, including quantity and reactivity to eye opening, was substrate
      specific. It was highly concordant with temporal spiking (60%), without any
      difference across the three groups, but provided additional information in 19
      (15%) patients who had no lateralizing spikes. The effect of sleep also was
      similar in all three groups and included transition of slow waves into spikes.
      Lateralized slow activity to the side of the operation was significantly
      associated with favorable outcome only in the group with nonspecific pathology (p
      = 0.008), regardless of the presence, laterality, or topography of spikes.
      CONCLUSIONS: Our findings suggest that in patients with TLE whose brain magnetic
      resonance imaging (MRI) is either normal or suggestive of medial temporal
      sclerosis, interictal temporal slow activity has a lateralizing value similar to
      that of temporal spiking. Its association with a favorable outcome in patients
      with nonspecific pathology also suggests that candidates with lateralizing
      temporal delta and normal MRI should not be barred from further preoperative
      assessment.

PMID- 15509237
TI  - SEEG-guided RF thermocoagulation of epileptic foci: feasibility, safety, and
      preliminary results.
AB  - PURPOSE: Depth electrodes recordings may be required in some cases of epilepsy
      surgery to delineate the best region for cortical resection. We usually implant
      depth electrodes according to Talairach's stereoelectroencephalography (SEEG)
      method. By using these permanently implanted depth electrodes, we are able to
      perform radiofrequency (RF)-thermolesions of the epileptic foci. We report the
      technical data required to perform such multiple cortical thermolesions, as well
      as preliminary results in terms of seizure outcome in a group of 20 patients.
      METHODS: Lesions were performed by using 100- to 110-mA bipolar current (50 V),
      applied for 10 to 50 s. Each thermocoagulation produced a 5- to 7-mm diameter
      cortical lesion. In total, two to 16 lesions were performed in each of the 20
      patients. Lesions were placed without anesthesia. No general or neurologic
      complication occurred during the procedures. Two transient postprocedure side
      effects, consisting of paresthetic sensations in the mouth and mild apraxia of
      the hand, were observed. RESULTS: At a follow-up time of 8 to 31 months (mean, 19
      months), 15% of the patients became seizure free, 40% experienced a > or =80%
      reduction of their seizure frequency, and 45% were not significantly improved.
      CONCLUSIONS: SEEG-guided RF thermolesions is a safe technique. Our preliminary
      results indicate that such lesions can lead to a significant reduction of seizure
      frequency and could be proposed as a palliative procedure if no resective surgery
      is possible. A randomized controlled trial is needed to determine which patients
      are likely to respond to SEEG-guided RF thermolesions.

PMID- 15509238
TI  - The nonmalformed hemisphere is secondarily impaired in young children with
      hemimegalencephaly: a pre- and postsurgery study with SPECT and EEG.
AB  - PURPOSE: To study separately the functional value of each cerebral hemisphere in
      hemimegalencephaly (HME). HME is a unique model of unilateral hemispheric lesion,
      but one suspects that the non-HME hemisphere also could be functionally impaired
      because the postsurgery outcome is less favorable than expected. METHODS: We
      performed simultaneous prolonged EEG and 133-xenon SPECT (single-photon emission
      computed tomography); we measured the absolute values of cerebral blood flow
      (CBF) in both hemispheres and compared them with the normal values previously
      acquired. Thirteen patients (aged 5-38 months) underwent 31 examinations, 20
      before surgery (hemispherotomy) and 11 after. RESULTS: In the HME hemisphere, we
      confirmed the presurgical mixture of increased and decreased CBF due to
      intermittent ictal discharges. After surgery, CBF was decreased in most cases. In
      the non-HME hemisphere, presurgery CBF was abnormal in 60% of the patients,
      increased and related mostly to diffuse interictal spikes on the same side,
      whereas normal CBF cases had focal spikes. After surgery, CBF was normal in 82%
      of cases, corresponding to an EEG without diffuse spikes. In the six patients
      longitudinally studied, CBF dramatically decreased after surgery in the HME
      hemisphere, whereas in the non-HME hemisphere, CBF was mostly normal very early
      (three fourths before 2 months), increased as soon as 3 months, and normalized
      only after hemispherotomy, the more rapidly the child was operated on, the
      earlier it was. CONCLUSIONS: This study shows that the function of the
      nonmalformed hemisphere is impaired as soon as the first months of the course of
      HME but can be restored after surgery. Our data support the recommendations to
      operate on the children as early as possible.

PMID- 15509239
TI  - Survival analysis of the surgical outcome of temporal lobe epilepsy due to
      hippocampal sclerosis.
AB  - PURPOSE: Surgical results in patients with mesial temporal lobe epilepsy due to
      hippocampal sclerosis (MTLE/HS) are often reported in conjunction with other
      etiologies of TLE. METHODS: We prospectively collected surgical outcome data for
      2 to 11 years for 134 consecutive patients who specifically had MTLE and
      unilateral HS, according to magnetic resonance imaging (MRI) and confirmed by
      histopathology. Sixty-five had postoperative neuropsychological testing. Outcome
      was analyzed by using Engel's classification (a) through Kaplan-Meier estimated
      survival curves (as a function of the time to seizure recurrence), (b) as
      percentage of patients in each outcome class on a yearly basis, and (c) at the
      last updated follow-up. RESULTS: Kaplan-Meier estimates of complete seizure
      freedom (Engel's class IA) for years 1, 2, 5, and 10 were 85%, 77%, 74%, and 66%,
      and of Engel's class I were 89%, 86%, 83%, and 81%. Only nine (6.7%) patients had
      outcome classes III or IV at any point during follow-up. Of the patients tested,
      26% of those operated on the left side and 22% of those operated on the right had
      postoperative decline of >1 SD in verbal or visual memory, respectively.
      CONCLUSIONS: High rates of seizure freedom can be obtained and remain stable over
      the years in patients operated on for unilateral MTLE/HS, even in countries with
      limited resources.

PMID- 15509240
TI  - Memory in patients with drug-responsive mesial temporal lobe epilepsy and
      hippocampal sclerosis.
AB  - PURPOSE: Mesial temporal lobe epilepsy associated with hippocampal sclerosis
      (MTLE-HS) is the most common of the antiepileptic drug (AED)-resistant seizure
      syndromes that are remediable mostly with surgery, although a small group of
      patients have benign prognosis with fewer seizures. Material-specific memory
      impairment is an important feature in these patients and may be related to both
      the structural abnormality and the frequent seizures. In this study, we
      investigated the relation between memory deficit and HS by taking seizure
      frequency into account. METHODS: The patients were evaluated according to a
      standard protocol and divided into two groups, considering their response to
      AEDs: the good-responder group (GRg, n = 18) and the pharmacoresistant group
      (PRg, n = 95). They were administered a neuropsychological test battery that
      included verbal and nonverbal memory tests, compared with each other and with a
      normal control group (n = 29). The responder group was evaluated by the same
      battery once again (mean, 23 months; SD, 8.25; range, 14-38 months). RESULTS:
      Both GR and PR patient groups had poorer memory than the normal controls in all
      memory tests (p < 0.05). However, the comparison of GRg with PRg revealed that
      only the digit-span test was significantly worse in PRg (p = 0.0061), and no
      difference was found in any other memory scores. The reevaluation of the GRg
      showed no significant difference between the first and second evaluation.
      CONCLUSIONS: We concluded that the memory impairment in patients with MTLE-HS was
      permanent and might be related to the direct effect of HS itself. Therefore
      patients with good response to AEDs can be used as a model for investigating the
      memory problems in patients with MTLE-HS.

PMID- 15509242
TI  - Public knowledge, private grief: a study of public attitudes to epilepsy in the
      United Kingdom and implications for stigma.
AB  - PURPOSE: For many people with epilepsy, the continuing social reality of their
      condition is as a stigma, thus representing a source of much private grief. To
      understand fully the nature of epilepsy stigma, it is important to examine
      attitudes and beliefs of not just the "targets" but also of the "perceivers" of
      stigma. Perceivers may hold erroneous beliefs and stereotypes that lead them to
      have negative expectations of people affected by epilepsy. This study examined
      levels of knowledge and attitudes among perceivers of epilepsy stigma in the U.K.
      METHODS: A random sample of >1,600 members of the general public was interviewed
      as part of the bimonthly UK Omnibus Survey. The response rate was 62%. RESULTS:
      One fourth of informants knew someone with epilepsy and one half had witnessed a
      seizure. One half agreed that people with epilepsy are treated differently by
      others, and themes of exclusion, restriction, and nonnormality were commonly
      cited as reasons for this. Epilepsy ranked second in a range of health
      conditions, in terms of which would cause them greatest concern if informants had
      to work with someone so affected. Responses to a series of attitude statements
      indicated that most held highly favorable attitudes; but one fifth agreed with
      the statement that people with epilepsy have more personality problems than do
      others. Responses were influenced by informants' sociodemographic
      characteristics. CONCLUSIONS: The survey revealed attitudes and knowledge gaps
      that have the potential for discriminatory behavior. There are implications for
      how public education campaigns should be implemented, and who should be targeted.

PMID- 15509241
TI  - Subjective sleep disturbance in patients with partial epilepsy: a questionnaire
      based study on prevalence and impact on quality of life.
AB  - PURPOSE: This study was designed to assess whether sleep disturbance is more
      frequent among patients with partial seizures and what impact on quality of life
      (QoL) sleep disturbance may have on patients with partial seizures. METHODS:
      Questionnaire booklets were mailed to 1,183 patients from four Dutch clinics.
      Each patient was asked to find two age- and gender-matched controls to complete
      the same set of questionnaires [Sleep Diagnosis List (SDL), Medical Outcomes
      Study (MOS)-Sleep Scale, Groningen Sleep Questionnaire, Epworth Sleepiness Scale,
      and the SF-36 Health Survey]. The prevalence of sleep disturbance, based on the
      SDL, was compared between those with partial epilepsy and controls. Mean scores
      on sleep and the SF-36 Physical (PCS) and Mental (MCS) Component Summary scales
      were compared. RESULTS: Responses from 486 patients and 492 controls were
      analyzed. Respondents with partial epilepsy had a highly significant, twofold
      higher prevalence of sleep disturbance compared with controls (38.6 vs. 18.0%; p
      < 0.0001). Most sleep-disorder subscales showed significant abnormalities in
      respondents with epilepsy, compared with controls. Mean SF-36 MCS and PCS scores
      were significantly lower in respondents with epilepsy compared with controls in
      both the strata with sleep disturbance and without (all p values <0.05). The
      presence of a sleep disturbance in respondents with epilepsy was associated with
      the greatest impairment in QoL. CONCLUSIONS: Sleep disturbance is more than twice
      as prevalent in persons with partial epilepsy compared with controls, and most
      domains of sleep are significantly disturbed. Persons with partial epilepsy have
      significant QoL impairment, and sleep disturbance further compounds this.

PMID- 15509243
TI  - A proposal for case definitions and outcome measures in studies of infantile
      spasms and West syndrome: consensus statement of the West Delphi group.
AB  - PURPOSE: To reach a broad consensus on case definitions, outcomes, and outcome
      measures that will ease future study design and facilitate comparison of data
      from different studies of infantile spasms and West syndrome. METHODS: Persons
      who had recently presented or published first-author original research in this
      field were invited to participate in an e-mail Delphi process and to invite other
      investigators or clinicians who they thought might participate. RESULTS: The
      process consisted of six rounds, anonymous except to the facilitator. In total,
      responses were received from 46 participants. The final statement was approved by
      31 participants from 15 countries. It concluded that the primary clinical
      outcome, cessation of spasms, should denote absence of witnessed spasms from
      within 14 days of commencement of treatment, and for > or =28 consecutive days
      from the last witnessed spasm. Primary electroclinical outcome denotes cessation
      of spasms with resolution of hypsarrhythmia. West syndrome should be a defined
      subset of the syndrome of infantile spasms. An infantile spasms single-spasm
      variant should be recognized. Ways are suggested of handling subtle spasms in the
      context of clinical studies. It proposes a standard for reporting modifying and
      atypical features of hypsarrhythmia, a minimal set of baseline characteristics
      and outcomes that should be reported in trials of infantile spasms, and suggests
      a standard definition of relapse. Consensus was not reached on a definition of
      hypsarrhythmia. CONCLUSIONS: We reached a clear consensus on many aspects of
      study design for the investigation of infantile spasms, although incomplete
      consensus was found on how to define EEG criteria.

PMID- 15509244
TI  - Genetic association studies in epilepsy: "the truth is out there".
AB  - Success has been achieved in identifying many mutations in rare monogenic
      epilepsy syndromes by using linkage analysis, but dissecting the genetic basis of
      common epilepsy syndromes has proven more difficult. Common epilepsies are
      genetically complex disorders believed to be influenced by variation in several
      susceptibility genes. Association studies can theoretically identify these genes,
      but despite more than 50 association studies in epilepsy, no consistent or
      convincing susceptibility genes have emerged, leading to scepticism about the
      association-study approach. We review the results of existing association studies
      in focal epilepsies, generalized epilepsies, febrile seizures, and epilepsy
      pharmacogenetics. By using an illustrative example, we discuss how methodologic
      issues of sample size, selection of appropriate controls, population
      stratification, and significance thresholds can lead to bias and false-positive
      associations; the importance of biologic plausibility also is emphasized. Newer
      methodologic refinements for association studies, such as use of two control
      groups, genomic control, haplotyping, and use of two independent datasets, are
      discussed. A summary of existing guidelines and a checklist for planning and
      appraising such association studies in epilepsy is presented. We remain
      cautiously optimistic that with methodologic refinements and multicenter
      collaborations with large sample sizes, association studies will ultimately be
      useful in dissecting the genetic basis of common epilepsy syndromes.

PMID- 15509245
TI  - Carbamazepine enhances discriminative memory in a rat model of epilepsy.
AB  - PURPOSE: Seizures and antiepileptic drugs (AEDs) are the main causes for
      cognitive impairment in persons with epilepsy. It is still a matter of debate
      whether carbamazepine (CBZ) improves cognition because of its own psychotropic
      effects or because it is more effective to treat temporal epilepsy. Our objective
      was to analyze the performance of CBZ-treated or nontreated pilocarpine epileptic
      rats in an object-recognition test. METHODS: Twelve chronic pilocarpine-induced
      epileptic rats were treated with CBZ, 40 mg/kg, or saline, t.i.d. for 8 days.
      Twenty-one nonepileptic controls were treated with CBZ or saline. On day 8 of
      treatment, all rats were tested with an object-recognition paradigm. RESULTS: No
      locomotor impairment was detected in chronic epilepsy or CBZ treatment, as
      exploration during training was not affected. Exploratory behaviors during the
      choice session were not decreased in rats treated with CBZ; therefore CBZ does
      not compromise procedural memory. Epileptic rats showed a nonsignificant change
      in the discrimination performance, and prolonged treatment with CBZ in epileptic
      rats induced a significant increase in object discrimination during the choice
      session. CONCLUSIONS: Even though pilocarpine-induced epileptic animals do not
      show compromised performance in the spontaneous object-recognition test,
      prolonged CBZ treatment has a positive effect on a simple object-discrimination
      task. These results may be associated with the psychotropic effects of CBZ.

PMID- 15509247
TI  - Inadequacy of standard screen resolution for localization of seizures recorded
      from intracranial electrodes.
AB  - Seizures recorded during long-term monitoring with implanted intracranial
      electrodes are typically interpreted by visual inspection alone by using digital
      display systems. When high-frequency activity is digitized and displayed on a
      typical monitor, it is altered in ways that are not always appreciated and that
      may have an impact on the intracranial EEG (ICEEG) interpretation. We describe a
      case of a neocortical-onset seizure in which false localization occurred with a
      12-s per screen display. Because frequencies in excess of 100 Hz are not uncommon
      in neocortical seizures, at most 4 to 5 s of EEG, depending on the screen
      resolution, data-sampling rate, and other factors, should be displayed at one
      time during visual interpretation to localize the seizure onset. Alternatively,
      spectral analysis should be performed on recordings of neocortical seizures to
      detect high-frequency activity that may be missed on visual inspection.

PMID- 15509246
TI  - Topiramate pharmacokinetics in children with epilepsy aged from 6 months to 4
      years.
AB  - PURPOSE: To study the pharmacokinetics of topiramate (TPM) at steady state in
      children younger than 4 years comedicated with other antiepileptic drugs (AEDs).
      METHODS: Twenty-two children aged 6 months to 4 years with pharmacoresistant
      partial or generalized epilepsy were enrolled in an open-label prospective study.
      Children were assigned to different groups according to comedication with enzyme
      inducing AEDs (n = 8), valproic acid (VPA) (n = 6), or other AEDs not known to
      affect drug metabolism (neutral AEDs, n = 7). One child was receiving treatment
      with both enzyme-inducing AEDs and VPA. After dose titration, blood samples were
      collected at steady state just before and 0.5, 1, 1.5, 2, 4, 6, 8, and 12 h after
      the morning dose of TPM. Pharmacokinetic parameters were determined by a
      noncompartmental method. RESULTS: TPM apparent oral clearance (CL/F) was
      significantly higher in children taking enzyme-inducing AEDs (85.4 +/- 34.0
      ml/h/kg) than in those receiving VPA (49.6 +/- 13.6 ml/h/kg) or neutral AEDs
      (46.5 +/- 12.8 ml/h/kg). Conversely, dose-normalized areas under the plasma TPM
      concentration curves (0-12 h) were significantly lower in enzyme-induced patients
      than in patients receiving VPA or other AEDs. CONCLUSIONS: Compared with children
      not receiving enzyme inducers, children younger than 4 years who receive
      concomitant enzyme-inducing AEDs need higher doses (milligrams per kilogram) to
      achieve comparable plasma TPM concentrations.

PMID- 15509248
TI  - A case of postictal transient anterograde and retrograde amnesia.

PMID- 15509249
TI  - Electrolyte therapy for refractory seizures in familial dysautonomia.
AB  - PURPOSE: Video-EEG in a family of three patients with slow development and
      familial dysautonomia demonstrated absence seizures associated with 3-Hz
      generalized spike-and-wave discharges. The seizures were refractory to
      antiepileptic drugs (AEDs). METHODS: Treatment was given with rice-based cereal
      electrolyte oral solution. RESULTS: Treatment induced seizure freedom and
      normalization of EEG in all three patients. Repeated video-EEG monitoring with
      discontinuation of AEDs and maintenance of the oral hydration therapy was
      associated with recurrence of epileptic activity. All three patients have
      remained seizure free (approximately 1 year) with a combination of topiramate and
      electrolytic therapy. CONCLUSIONS: Rice-based oral electrolyte hydration therapy
      may play a role in prevention and control of seizures in patients with familial
      dysautonomia.

PMID- 15509250
TI  - EURAP: an international registry of antiepileptic drugs and pregnancy.

PMID- 15509251
TI  - North American antiepileptic drug pregnancy registry.

PMID- 15509252
TI  - Australian pregnancy registry of women taking antiepileptic drugs.

PMID- 15509253
TI  - U.K. epilepsy and pregnancy group.

PMID- 15509254
TI  - The International Lamotrigine pregnancy registry update for the epilepsy
      foundation.

PMID- 15509256
TI  - Evaluation of the AQUARAPID-Va, AQUAEIA-Va and dot-blot assays for the detection
      of Vibrio anguillarum in fish tissues.
AB  - The comparative accuracy of the serological assays AQUARAPID-Va, AQUAEIA-Va
      (BIONOR AS), and dot-blot for a rapid diagnosis of vibriosis in fish was
      evaluated. Twenty-one Vibrio anguillarum strains, representative of pathogenic
      and environmental serotypes, and 13 strains of other fish pathogenic bacteria
      were used to assess the sensitivity and specificity of the detection methods. The
      serological assays tested detected all the strains of V. anguillarum serotypes O1
      and O2. The dot-blot assay was the most specific and sensitive method, detecting
      almost all isolates from serotypes O1, O2 and O3, with an average sensitivity of
      1 x 10(6) bacteria g(-1) of fish tissue. The AQUARAPID-Va and the AQUAEIA-Va
      systems were able to detect 5 x 10(6) and 5 x 10(7) bacteria g(-1) of fish
      tissue, respectively. The simplicity, effectiveness and speed of the AQUARAPID-Va
      system confirmed this method as the most suitable serological test for the
      detection of V. anguillarum in field analysis and small-scale laboratory studies.

PMID- 15509257
TI  - Immune responses of barramundi, Lates calcarifer (Bloch), after administration of
      an experimental Vibrio harveyi bacterin by intraperitoneal injection, anal
      intubation and immersion.
AB  - Barramundi, Lates calcarifer (Bloch), were immunized with an experimental Vibrio
      harveyi bacterin via intraperitoneal injection, immersion and anal intubation.
      Both specific and non-specific immune parameters were measured to compare
      responses to bacterin after delivery by various methods. Elevated antibody
      activities in sera were found in all treatment groups with barramundi injected
      intraperitoneally displaying significantly higher antibody activity than the
      other groups. In addition, there was evidence of memory induction with a
      heightened antibody response in the intraperitoneally injected group only.
      Bacteriostatic assays indicated activity against V. harveyi in the sera of all
      bacterin-treated groups; again this activity was significantly higher in the
      intraperitoneally injected groups. There was no enhancement noted in head kidney
      macrophage phagocytic activity or in serum lysozyme levels.

PMID- 15509258
TI  - Aquabirnaviruses isolated from marine organisms form a distinct genogroup from
      other aquabirnaviruses.
AB  - A phylogenetic tree of aquabirnaviruses, including marine birnaviruses (MABV) and
      infectious pancreatic necrosis virus (IPNV), was developed based on the
      nucleotide sequences and deduced amino acid sequences of the polyprotein and VP5
      genes of genomic segment A. In the polyprotein of MABV strains, the amino acid
      sequences were very similar, with identities of 98.3-99.7%. Twenty-one unique
      amino acid residues were found in the deduced amino acid sequences of the
      polyprotein gene of MABV strains. The phylogenetic tree based on the nucleotide
      sequence of genomic segment A and polyprotein sequences showed that 31
      aquabirnavirus strains were clustered into seven genogroups. All MABV strains
      isolated in Japan and Korea were clustered into one genogroup which was distinct
      from other aquabirnaviruses. The seventh genogroup containing all MABV strains
      showed amino acid sequence similarities of 80.7-90.6% with other genogroups. In
      VP5, four unique residues were found in MABV strains when compared with IPNV
      strains. The MABV strains exhibited amino acid sequence similarities of 63.9
      86.4% with IPNV strains. The amino acid sequences of VP5 were conserved among
      MABV strains, but differed from those of IPNV strains. The MABV strains isolated
      from different host species and different geographical areas were very similar to
      each other, suggesting that the MABV are distinct from the other genogroups.

PMID- 15509260
TI  - Induction of apoptosis in a flounder gill cell line by lymphocystis disease virus
      infection.
AB  - Lymphocystis disease virus (LCDV), a large icosahedral DNA virus classified to
      the iridovirus family, is the causative agent of lymphocystis, a disease which
      occurs in marine and freshwater fish species and is characterized by formation of
      papilloma-like lesions on the surface of the skin. In vitro, LCDV infection
      causes flounder gill cells, an adherent cell line, to exhibit an obvious
      cytopathic effect (CPE). In order to test whether apoptosis is responsible for
      the observed CPE, cells infected with LCDV at a multiplicity of infection
      (m.o.i.) of 5 PFU per cell were examined at various time intervals for the
      appearance of apoptotic signs. Nuclear fragmentation, DNA laddering and caspase
      activation were observed in the infected cells at the time (i.e. 10 days post
      infection) when an intensive CPE was observed. These findings demonstrate that
      LCDV is capable of inducing apoptosis in vitro, which is different from the
      result of LCDV infection in vivo, and consequently suggest an intricate LCDV-host
      interaction.

PMID- 15509259
TI  - Experimental infection of turbot, Scophthalmus maximus (L.), by Moritella
      viscosa, vaccination effort and vaccine-induced side-effects.
AB  - Moritella viscosa is the causative agent of winter ulcers in farmed salmonids and
      Atlantic cod in countries around the North Atlantic. The bacterium has also been
      isolated from various marine fish species. Bacterial diseases have been a
      limiting factor in farming of turbot, but M. viscosa has not so far been
      isolated. In this study, turbot was shown to be sensitive to M. viscosa infection
      in experimental challenges. Pathological changes in infected turbot were
      comparable with those previously described for winter ulcers in salmon. A
      multivalent commercial salmon vaccine, containing M. viscosa as one of five
      antigens and a mineral oil adjuvant, did not protect turbot against challenge 13
      weeks post-vaccination. Weight gain of vaccinated turbot compared with controls
      was not reduced 7 weeks post-vaccination. Vaccination did not induce a specific
      anti-M. viscosa response, while elevated anti-M. viscosa antibody levels were
      detected both in vaccinated and unvaccinated fish 5 weeks post-challenge. The
      vaccine did, however, induce an antibody response against Aeromonas salmonicida,
      another vaccine component. Minor intra-abdominal adhesions were detected in
      vaccinated fish and fish injected with a mineral oil adjuvant. The measurement of
      various innate humoral immune parameters did not reveal significant differences
      between vaccinated and control groups.

PMID- 15509261
TI  - The relationships between fish health, metabolic rate, swimming performance and
      recovery in return-run sockeye salmon, Oncorhynchus nerka (Walbaum).
AB  - The repeat swimming ability and oxygen uptake (Mo2) of adult sockeye salmon,
      Oncorhynchus nerka (Walbaum), were assessed at ambient water temperatures at
      three field locations along their migration route. Following these measurements,
      internal and external fish condition was evaluated according to United States
      Environmental Protection Agency guidelines. Here we report on the physiological
      characteristics of fish having either moderate or severe levels of disease and
      injury. Routine oxygen uptake (Mo2) did not differ between healthy fish and those
      with indices of ill health. In contrast, fish classified as sick, which included
      conditions of damaged internal organs, an Ichthyophonus spp. heart infection, a
      Saprolegnia spp. gill infection, and skin wounds, had a lower post-exercise Mo2
      and were unable to repeat their critical swim speed (U(crit)) on the second swim
      test. Moderate levels of disease or injury did not significantly affect either
      U(crit) or post-exercise Mo2. We conclude that the ability of adult salmon to
      recover quickly from exercise may be a useful indicator of sublethal pathologies.

PMID- 15509262
TI  - Effect of dietary iron overload on Photobacterium damselae ssp. piscicida
      pathogenicity in sea bass, Dicentrarchus labrax (L.).

PMID- 15509264
TI  - Editorial. Special issue on the nursing workforce and quality of care.

PMID- 15509265
TI  - Commentary. Nursing skill mix and staffing.

PMID- 15509266
TI  - Commentary. Nurse workforce planning in the UK: policies and impact.

PMID- 15509267
TI  - Commentary. The contribution of universities to the development of the nursing
      workforce and the quality of patient care.

PMID- 15509268
TI  - Can we measure how changes in the nursing workforce affect patient care?
AB  - Ward staff are the largest staff group in the hospital workforce and constitute
      the biggest budget item for most acute trusts. The nature of the ward workforce
      has changed considerably in the last 30 years but it is unclear what impact the
      changes have had on patient care. Understanding the link between resources and
      staffing levels on the one hand and outputs and outcomes for patients on the
      other is vital, particularly if further changes to the workforce are planned. In
      order to explore them, this article examines: (1) some of the reasons for changes
      to the workforce, (2) some of the research already available, and (3) the nature
      of research and information required. Finally, it looks at the work that the
      Audit Commission carried out in 2000 and which is currently being repeated by the
      Healthcare Commission.

PMID- 15509269
TI  - Using indicator development to revise infection control activities in an acute
      NHS trust.
AB  - AIM: This paper describes a 2-year project to facilitate improved infection
      control within an acute National Health Service trust. BACKGROUND: Organizational
      support, broad ownership of issues and adequate resources are needed to enable
      good infection control to underpin improvements in care. METHOD: Development of
      indicators, agreed at a stakeholder workshop, was used as a focus. The Infection
      Control Team was expanded. RESULTS: The team has a wider skills base and can
      deliver proactive and reactive services in closer collaboration with clinicians,
      especially modern matrons. The infection control committee has been reconstituted
      and become more effective. There have been demonstrable health and financial
      gains over 2 years, and improved performance against national standards.
      CONCLUSION: Focusing on indicator development enabled key stakeholders to gain a
      collective appreciation of the issues that the trust faced, increased ownership
      of agreed actions and rooted infection control activity in trust mechanisms for
      monitoring and business planning.

PMID- 15509270
TI  - Use, misuse and non-use of health care assistants: understanding the work of
      health care assistants in a hospital setting.
AB  - AIM(S): This study is concerned with understanding the work of non-registered
      nurses (health care assistants) in a UK hospital setting. BACKGROUND: There are
      increasing numbers of health care assistants employed by the National Health
      Service in the UK to support registered nurses providing nursing care. However,
      little is known about the make-up of the health care assistant workforce and the
      changing nature of their role. This study addresses some of these gaps in the
      research-based literature. METHODS: A single case study design using mixed
      methods (survey, interviews, participant observations, focus groups and
      documents) was used to generate an in-depth account of health care assistants'
      work in one organization. The study is built upon what health care assistants say
      they do, compared with what they actually do in practice. It explores how and
      whether the work of health care assistants is adequately supervised, tensions
      between the work of health care assistants and registered nurses and the
      subsequent effects on teamwork and patient care. FINDINGS: There are policy
      expectations associated with the work of health care assistants. However, this
      study reveals significant deviations from these goals. The workplace arena and
      the negotiations between health care assistants and registered nurses that take
      place within it, actively shape the health care assistants' work. Findings
      suggest dynamic patterns of use, misuse and non-use of the health care assistants
      as a resource to patient care. DISCUSSION AND IMPLICATIONS FOR PRACTICE: The
      changing roles of registered nurses have direct implications for the roles of
      health care assistants: as registered nurses take on extra duties and
      responsibilities they are conceding some of their role to health care assistants.
      This has implications for nurse managers. The competence of health care
      assistants to carry out nursing work needs to be reassessed and there also needs
      to be ongoing monitoring and supervision of their work to maximize, and further
      develop, their contribution to patient care and to ensure quality standards.
      Managers also need to be aware of the importance of workplace negotiations in the
      interpretation of formal policies and the subsequent shaping of health care
      assistants' work at the level of service delivery.

PMID- 15509271
TI  - The modern matron: a hybrid management role with implications for continuous
      quality improvement.
AB  - This paper describes the second phase of a research study into the introduction
      of the 'modern matron' role in the National Health Service. It draws on
      information from a survey of modern matrons in 10 case study trusts and from
      semistructured interviews with purposively selected matrons and their key
      contacts. Three models of role implementation are identified, each typical of
      'hybrid management' but with different emphases on matrons' professional
      (clinical) and corporate management responsibilities. There is evidence that
      matrons are starting to make an impact on different aspects of quality
      improvement in their trusts, but this is often limited by lack of forethought
      about where they should be located in the organization. It is suggested that,
      before making decisions about establishing modern matron posts, trusts need to
      have a clearer understanding both of the different contributions matrons can make
      to quality improvement and the challenges posed by this type of role.

PMID- 15509273
TI  - Learning for clinical leadership.
AB  - Clinical leadership has been acclaimed widely as a major factor influencing the
      quality of patient care but research has revealed a paucity of preparation for
      this significant role. Leadership literature has rarely addressed clinical
      leadership specifically or referred to the difficulties in characterizing
      effective clinical leaders. The research informing this paper focused on clinical
      leadership and identified five attributes of effective clinical leaders:
      creativity, highlighting, influencing, respecting, and supporting. Effective
      clinical leaders adopted a transformational leadership style and improved care,
      through others, by including transformational (soft) knowledge as an integral
      part of their effective practice repertoire. Phronesis is introduced as practical
      wisdom that is gained through immersion in relevant experience, and as an
      essential element of preparation for clinical nursing leadership practice. It is
      argued, that learning to transform care requires opportunities to work within an
      environment that engenders and supports aspiring leaders. The paper describes the
      research process, elucidates the attributes through illustrative examples from
      the research data, and discusses an emergent educational strategy for the
      development of these attributes by clinicians in their practice environments. The
      paper also describes the application of this research through an
      interdisciplinary programme for staff leading teams in both health and social
      services sectors.

PMID- 15509272
TI  - Using clinical performance information to improve the quality of care in a
      specialist NHS trust.
AB  - This article offers a case study of how an National Health Service trust
      specializing in neurology and neurosurgery used clinical performance information
      to underpin its quality improvement strategy. This involved developing a clinical
      effectiveness framework and identifying trust-specific clinical indicators, an
      exercise which involved both staff and patients. Writing from personal experience
      as clinical effectiveness manager, the author argues that clinical indicators can
      be powerful tools for monitoring the quality and effectiveness of health care at
      a system-wide level. In the case of nursing care, the use of appropriate, nursing
      sensitive indicators can provide a valuable complement to the qualitative
      information generated by the benchmarking approach used in 'Essence of Care'. The
      article contains details of the sort of problems encountered along the way--such
      as resistance from clinicians and general managers, and difficulties with the
      existing information technology infrastructure--and suggests how other trusts
      might approach them.

PMID- 15509274
TI  - Innovative leadership and management in a nursing home.
AB  - The Australian Aged Care Reform Package, implemented from October 1997, has led
      radical changes in nursing practice in residential aged care facilities. Apart
      from anecdotal evidence, however, little is known about the impact of the Reform
      Package on nursing staff and their practice in nursing home facilities. In an
      attempt to explore these issues a qualitative explorative research study was
      conducted in one nursing home during 2000-2001. The study found that the impact
      of policy change on nursing staff and their practice depended on the management's
      leadership in interpreted the new policy and implemented innovative strategies in
      order to meet its requirements. The findings of the study highlight management's
      'no them vs. us' and 'holistic' approach that considered both nursing staff and
      residents as whole beings. Integral to this approach was management's recognition
      that in order to facilitate teamwork, appropriate standards of nursing practice
      and resident care, and staff job satisfaction four resource elements must be
      provided. These elements comprise material, environmental, psychosocial and
      psychological resources. Management's provision of each of these resources
      ensured that nurses considered this nursing home 'a nice place to work'.

PMID- 15509275
TI  - Patient safety and quality of care: the role of the health care assistant.
AB  - The role of the Health Care Assistant emerged primarily to support the
      professional nurse and to undertake perceived 'non-nursing' duties under the
      direction and supervision of qualified nurses. Health Care Assistants are
      employed in a variety of clinical settings and carry out a range of tasks and
      procedures. While they represent a substantial proportion of the health care
      workforce, the growth of their role has taken place without regulation, clear
      boundaries, or systematic education and training. This has raised serious
      concerns, especially with regard to the issues of patient safety and quality of
      care. For health professionals, regulations, role clarity and validated education
      and training are key elements of ensuring the safety of the public. This paper
      explores these issues with regard to the Health Care Assistant role and finds
      them wanting.

PMID- 15509276
TI  - Conference report. Current research on nursing workforce issues.

PMID- 15509277
TI  - Emotions, personality, and health: introduction to the special issue.
AB  - Our intent in this introduction to the special issue on Emotions, Personality,
      and Health is to alert readers to the logic underlying the editors' choices of
      topics for the issue and to provide a brief summary of its contents. We discuss
      how the 10 articles fit together to provide a mosaic of diverse approaches to the
      study of emotion. Collectively, these articles show ways that emotion research
      may be integrated with personality theory to inform us about the psychological
      dimensions of health and illness.

PMID- 15509278
TI  - Functional brain mapping of extraversion and neuroticism: learning from
      individual differences in emotion processing.
AB  - This review outlines how functional brain imaging, using an individual
      differences approach in the processing of emotional stimuli, has begun to reveal
      the neural basis of extraversion (E) and neuroticism (N), two traits that are
      linked to both emotion and health. Studies using functional magnetic resonance
      imaging have shown that individual differences in participants' E and N scores
      are correlated with individual differences in brain activation in specific brain
      regions that are engaged during cognitive-affective tasks. Imaging studies using
      genotyped participants have begun to address the molecular mechanisms that may
      underlie these individual differences. The multidisciplinary integration of brain
      imaging and molecular genetic methods offers an exciting and novel approach for
      investigators who seek to uncover the biological mechanisms by which personality
      and health are interrelated.

PMID- 15509279
TI  - Chronic pain, stress, and the dynamics of affective differentiation.
AB  - We describe a program of research examining how the relationship between positive
      and negative affect varies both between individuals and within individuals over
      time. This Dynamic Model of Affect (DMA) proposes that under conditions that
      promote maximal information processing, positive and negative affective systems
      function relatively independently. In contrast, under conditions characterized by
      uncertainty, including pain and stress, the affects become strongly inversely
      related. Included in our consideration are potential individual differences in
      the ability to sustain affective differentiation during pain and other stressors
      and the implications of this model for perceptions of social relations and for
      interventions to improve well-being among the chronically ill.

PMID- 15509280
TI  - Psychological resilience and positive emotional granularity: examining the
      benefits of positive emotions on coping and health.
AB  - For centuries, folk theory has promoted the idea that positive emotions are good
      for your health. Accumulating empirical evidence is providing support for this
      anecdotal wisdom. We use the broaden-and-build theory of positive emotions
      (Fredrickson, 1998; 2001) as a framework to demonstrate that positive emotions
      contribute to psychological and physical well-being via more effective coping. We
      argue that the health benefits advanced by positive emotions may be instantiated
      in certain traits that are characterized by the experience of positive emotion.
      Towards this end, we examine individual differences in psychological resilience
      (the ability to bounce back from negative events by using positive emotions to
      cope) and positive emotional granularity (the tendency to represent experiences
      of positive emotion with precision and specificity). Individual differences in
      these traits are examined in two studies, one using psychophysiological evidence,
      the second using evidence from experience sampling, to demonstrate that positive
      emotions play a crucial role in enhancing coping resources in the face of
      negative events. Implications for research on coping and health are discussed.

PMID- 15509282
TI  - Hostility, anger, aggressiveness, and coronary heart disease: an interpersonal
      perspective on personality, emotion, and health.
AB  - The related traits of hostility, anger, and aggressiveness have long been
      suggested as risk factors for coronary heart disease (CHD). Our prior review of
      this literature (Smith, 1992) found both considerable evidence in support of this
      hypothesis and important limitations that precluded firm conclusions. In the
      present review, we discuss recent research on the assessment of these traits,
      their association with CHD and longevity, and mechanisms possibly underlying the
      association. In doing so, we illustrate the value of the interpersonal tradition
      in personality psychology (Sullivan, 1953; Leary, 1957; Carson, 1969; Kiesler,
      1996) for not only research on the health consequences of hostility, anger, and
      aggressiveness, but also for the general study of the effects of emotion,
      personality and other psychosocial characteristics on physical health.

PMID- 15509281
TI  - When the social self is threatened: shame, physiology, and health.
AB  - Our program of research focuses on shame as a key emotional response to "social
      self" threats (i.e., social evaluation or rejection). We propose that shame may
      orchestrate specific patterns of psychobiological changes under these conditions.
      A series of studies demonstrates that acute threats to the social self increase
      proinflammatory cytokine activity and cortisol and that these changes occur in
      concert with shame. Chronic social self threats and persistent experience of
      shame-related cognitive and affective states predict disease-relevant
      immunological and health outcomes in HIV. Across our laboratory and longitudinal
      studies, general or composite affective states (e.g., distress) are unrelated to
      these physiological and health outcomes. These findings support a stressor- and
      emotional response-specificity model for psychobiological and health research.

PMID- 15509283
TI  - Alexithymia, emotional disclosure, and health: a program of research.
AB  - This article reviews a program of research on alexithymia, emotional disclosure,
      and health. The article first describes two lines of research and then outlines
      current work attempting to integrate these lines. The first research line
      involves basic correlational studies on alexithymia's link to health problems;
      these studies suggest that alexithymia is a potential risk factor for symptoms
      and illness behavior, although not necessarily organic disease. The second
      research line involves experimental studies of the health effects of emotional
      disclosure via expressive writing or talking; these studies suggest that
      disclosure improves health on average, but that the effects are not that robust
      and that various moderators likely are involved. The next section of the article
      describes recent attempts to integrate the two research lines by examining how
      baseline levels of alexithymia influence the effects of emotional disclosure;
      these analyses suggest that alexithymia interferes with or attenuates the health
      benefits of disclosure. Finally, the article describes initial forays into
      research on interventions with the alexithymic patients. This evolving program of
      research demonstrates the value of integrating emotion, personality, and health,
      and highlights the bidirectional relationship between clinical problems and basic
      research.

PMID- 15509284
TI  - Healthy and unhealthy emotion regulation: personality processes, individual
      differences, and life span development.
AB  - Individuals regulate their emotions in a wide variety of ways. Are some forms of
      emotion regulation healthier than others? We focus on two commonly used emotion
      regulation strategies: reappraisal (changing the way one thinks about a
      potentially emotion-eliciting event) and suppression (changing the way one
      responds behaviorally to an emotion-eliciting event). In the first section, we
      review experimental findings showing that reappraisal has a healthier profile of
      short-term affective, cognitive, and social consequences than suppression. In the
      second section, we review individual-difference findings, which show that using
      reappraisal to regulate emotions is associated with healthier patterns of affect,
      social functioning, and well-being than is using suppression. In the third
      section, we consider issues in the development of reappraisal and suppression and
      provide new evidence for a normative shift toward an increasingly healthy emotion
      regulation profile during adulthood (i.e., increases in the use of reappraisal
      and decreases in the use of suppression).

PMID- 15509285
TI  - Coping through emotional approach: a new look at emotion, coping, and health
      related outcomes.
AB  - Researchers studying stress and coping processes have attempted to identify which
      coping strategies are most adaptive in stressful encounters. A generally accepted
      conclusion has been that emotion-focused coping processes are associated with
      dysfunctional outcomes. Studies from our and other research teams challenge the
      "bad reputation" of emotion-focused coping by demonstrating that items measuring
      emotion-focused strategies in published coping questionnaires are confounded with
      distress and self-deprecation. We have developed and validated new instruments to
      assess coping though acknowledging, understanding, and expressing emotion, that
      is, coping through emotional approach. Longitudinal and experimental studies
      using these new scales have documented the adaptive potential of emotional
      approach coping in the context of several types of stressors, including
      infertility, breast cancer, and chronic pain. However, characteristics of the
      environmental context, stressful experience, and individual are important
      moderators of the relations of emotional-approach coping and health-related
      outcomes. Potential mediators and moderators of coping through emotional
      approach, clinical relevance of the construct, and directions for research are
      discussed.

PMID- 15509286
TI  - Early environment, emotions, responses to stress, and health.
AB  - A harsh early family environment is related to mental and physical health in
      adulthood. An important question is why family environment in childhood is
      associated with these outcomes so long after its initial occurrence. We describe
      a program of research that evaluates a model linking these variables to each
      other. Specifically, we hypothesize that low social competence and negative
      emotional states may mediate relations between a harsh early family environment
      and physiological/neuroendocrine responses to stress, as well as long-term health
      outcomes. We report evidence that the model characterizes self-rated health,
      cortisol responses to stress, and, in males only, elevated cardiovascular
      responses to stress. We discuss how the social context of early life (such as
      SES) may affect the family environment in ways that precipitate adverse health
      consequences. Perspectives on comorbidities in physical and mental health are
      discussed.

PMID- 15509287
TI  - Socioemotional selectivity theory, aging, and health: the increasingly delicate
      balance between regulating emotions and making tough choices.
AB  - After providing an introductory overview of socioemotional selectivity theory, we
      review empirical evidence for its basic postulates and consider the implications
      of the predicted cognitive and behavioral changes for physical health. The main
      assertion of socioemotional selectivity theory is that when boundaries on time
      are perceived, present-oriented goals related to emotional meaning are
      prioritized over future-oriented goals aimed at acquiring information and
      expanding horizons. Such motivational changes, which are strongly correlated with
      chronological age, systematically influence social preferences, social network
      composition, emotion regulation, and cognitive processing. On the one hand, there
      is considerable reason to believe that such changes are good for well-being and
      social adjustment. On the other hand, the very same motivational changes may
      limit health-related information-seeking and influence attention, memory, and
      decision-making such that positive material is favored over negative information.
      Grounding our arguments in socioemotional selectivity theory, we consider
      possible ways to tailor contexts such that disadvantages are avoided.

PMID- 15509288
TI  - Characteristics of the in vitro hypoxic pulmonary vasoconstrictor response in
      isolated equine and bovine pulmonary arterial rings.
AB  - OBJECTIVE: Hypoxaemia accompanies dorsal recumbency in the horse and frequently
      complicates general anaesthesia. The physiology associated with this phenomenon
      is poorly understood. One possible cause of poor tolerance to dorsal recumbency
      is an absent or reduced response to hypoxic pulmonary vasoconstriction (HPV).
      This study compared the HPV response in isolated pulmonary artery vessels from
      equivalent regions of equine and bovine lung. ANIMALS: Equine and bovine, in
      vitro study. MATERIALS AND METHODS: Equine and bovine pulmonary arteries were
      removed from the lungs of euthanased horses and cattle. Measurements of isometric
      tension were made on isolated rings of pulmonary vessels at 37 degrees C in a
      Krebs' saline solution. Hypoxia was induced by bubbling with a nominally 0% O(2)
      gas mixture. RESULTS: A significant HPV response was observed above a baseline
      tension induced by phenylephrine (PE; 0.3 microm) or 5-hydroxytryptamine (5-HT;
      0.1 microm). The HPV response in equine pulmonary vessels was approximately 33%
      less than the response observed in equivalent bovine vessels (equine 196 +/-
      20%versus bovine 290 +/- 32%; p < 0.05). Removal of the endothelium (by rubbing
      the luminal surface) significantly reduced but did not abolish the HPV response.
      Incubation with the nitric oxide (NO) synthase inhibitor N-nitro-l-arginine
      methyl ester (L-NAME; 100 microm), or COX-1/COX-2 inhibitor indomethacin (10
      microm) markedly attenuated the HPV response in equine vessels. CONCLUSIONS:
      These results suggest that a significant HPV response exists in isolated equine
      pulmonary vessels; a component of this response requires a functional
      endothelium. Inhibition of cyclooxygenase and NO synthase attenuated the
      response, suggesting the involvement of a COX product and/or NO in mediating this
      effect either directly or indirectly. Alternatively, a non-COX related action of
      the nonsteroidal anti-inflammatory drug, indomethacin, may be involved.

PMID- 15509289
TI  - Effects of syringe material and temperature and duration of storage on the
      stability of equine arterial blood gas variables.
AB  - OBJECTIVES: To evaluate the consistency of partial pressures (P) of arterial
      oxygen (aO(2)), arterial carbon dioxide (aCO(2)) and pH measurements in equine
      carotid arterial blood samples taken into syringes made from three different
      materials and stored at room temperature or placed in iced water for measurement
      at three different times. STUDY DESIGN: Prospective observational study over 19
      days. ANIMALS: Four clinically normal Thoroughbred or Thoroughbred-cross horses
      (three geldings, one mare, mean age 6.25 years, range 5-7 years). METHODS:
      Identical blood samples were taken on two separate occasions from the carotid
      arteries of the four horses into syringes made of glass, plastic and
      polypropylene. PaO(2), PaCO(2) and pH determinations were performed on blood from
      each syringe type at 10, 60 and 120 minutes post-sampling with samples stored at
      room temperature (approximately 20 degrees C) or in iced water (approximately 0
      degrees C). Data were analysed by anova and a split plot model fitting syringe
      within horse X pair and time within temperature within syringe. RESULTS: Syringe
      material, storage temperature and time before analysis all had significant
      effects on PaO(2) (p < 0.001). PaCO(2) was unaffected by syringe material or
      storage temperature. However, over 120 minutes, storage duration significantly (p
      = 0.002) affected values. Temperature of storage and duration prior to analysis
      both significantly affected pH values (p = 0.005 and p < 0.001, respectively),
      but syringe material did not. Several significant interactions between these
      variables were noted. CONCLUSIONS: Equine arterial blood gas determination has a
      different sensitivity to storage conditions compared to other veterinary species.
      CLINICAL RELEVANCE: For accurate equine arterial blood analysis, PaO(2) samples
      need to be analysed within 10 minutes or taken into glass syringes, stored on ice
      and analysed at 2 hours post-sampling. PaCO(2) and pH measurements can be
      performed on samples stored in glass, plastic or polypropylene syringes at room
      temperature for up to 1 hour post-sampling.

PMID- 15509290
TI  - Effects of doxapram HCl on laryngeal function of normal dogs and dogs with
      naturally occurring laryngeal paralysis.
AB  - OBJECTIVES: To compare the effects of IV doxapram on glottic size and arytenoid
      motion in normal dogs and in dogs with laryngeal paralysis. STUDY DESIGN:
      Prospective experimental and clinical trials. ANIMALS: Six healthy dogs weighing
      24.5 +/- 3.9 kg and six dogs weighing 27.4 +/- 11.5 kg suspected of having
      laryngeal paralysis. METHODS: Dogs were pre-medicated with acepromazine and
      butorphanol, and a light plane of anesthesia was induced with isoflurane by mask.
      Videoendoscopic examination of laryngeal function was recorded before (baseline)
      and after IV doxapram administration. Normalized glottal gap area (NGGA) at
      maximal inspiration and expiration, and percentage change in height, width, area,
      and NGGA were calculated with measurements from digitized images of the glottal
      gap. RESULTS: Active arytenoid motion was present in all normal dogs at baseline.
      After doxapram administration, depth of respiration appeared greater, but
      arytenoid motion, as measured by percentage change in NGGA, and in area and
      width, did not significantly increase in normal dogs. No arytenoid motion was
      detected in dogs with laryngeal paralysis at baseline; however, rima glottidis
      NGGA of dogs with laryngeal paralysis was greater at inspiration and expiration
      than normal dogs. After doxapram administration, dogs with laryngeal paralysis
      developed paradoxical arytenoid motion and significant, negative percentage
      change in area (-61%) and NGGA (-145%) because of inward collapse of the
      arytenoids during inspiration. CONCLUSIONS AND CLINICAL RELEVANCE: Administration
      of doxapram during laryngeal examination is useful for differentiating normal
      dogs from dogs with laryngeal paralysis. Dogs with laryngeal paralysis may suffer
      extreme glottic constriction with vigorous respirations, and may require
      intubation during examination.

PMID- 15509291
TI  - Effect of lidocaine on the minimum alveolar concentration of isoflurane in dogs.
AB  - OBJECTIVE: To determine the influence of a low-dose constant rate infusion (LCRI;
      50 microg kg(-1) minute(-1)) and high-dose CRI (HCRI; 200 microg kg(-1) minute(
      1)) lidocaine infusion on the minimum alveolar concentration (MAC) of isoflurane
      (I) in dogs. STUDY DESIGN: Prospective experimental study. ANIMALS: Ten mongrel
      dogs (four females, six males), weighing 20-26.3 kg. METHODS: Dogs were
      anesthetized with I in oxygen and their lungs mechanically ventilated. Baseline
      MAC was determined using mechanical or electrical stimuli. Lidocaine (2 mg kg(-1)
      IV) was administered over 3 minutes, followed by the LCRI and MAC determination
      commenced 30 minutes later. Once MAC was determined following LCRI, the lidocaine
      infusion was stopped for 30 minutes. A second bolus of lidocaine (2 mg kg(-1),
      IV) was administered, followed by the HCRI and MAC re-determined. Concentrations
      of lidocaine and its metabolites were measured at end-tidal I concentrations
      immediately above and below MAC. Heart rates and blood pressures were measured.
      RESULTS: Minimum alveolar concentration of I was 1.34 +/- 0.11 (%; mean +/- SD)
      for both types of stimulus. The LCRI significantly reduced MAC to 1.09 +/- 0.13
      (18.7% reduction) and HCRI to 0.76 +/- 0.10 (43.3% reduction). Plasma
      concentrations (ng mL(-1), median; value below and above MAC, respectively) for
      LCRI were: lidocaine, 1465 and 1537; glycinexylidide (GX), 111 and 181;
      monoethylglycinexylidide (MEGX), 180 and 471 and for HCRI were: lidocaine, 4350
      and 4691; GX, 784 and 862; MEGX, 714 and 710. Blood pressure was significantly
      increased at 30 minutes after high dose infusion. CONCLUSION AND CLINICAL
      RELEVANCE: Lidocaine infusions reduced the MAC of I in a dose-dependent manner
      and did not induce clinically significant changes on heart rate or blood
      pressure.

PMID- 15509292
TI  - Brachial plexus block using electrolocation for pancarpal arthrodesis in a dog.
AB  - Conduction blockade was achieved at the brachial plexus of a dog undergoing
      surgery for pancarpal arthrodesis. The lidocaine/bupivacaine mixture used was the
      sole analgesic treatment applied during surgery and for 3 hours post-operatively.
      Location of the plexus brachialis was facilitated using a nerve stimulator. A low
      volume of lidocaine and bupivacaine (0.26 mL kg(-1)) resulted in successful
      blockade, which was evident from stable cardiorespiratory variables at low end
      tidal (1.3-1.4%) isoflurane concentrations. Pain scoring and examination of motor
      and sensory function indicated adequate pain relief for 7 hours. While
      localization of the plexus brachialis can be performed 'blindly', electrolocation
      improves the success rate for less experienced anaesthetists.

PMID- 15509293
TI  - Neuroleptanalgesia in wild Asian elephants (Elephas maximus maximus).
AB  - OBJECTIVE: To evaluate the suitability of etorphine with acepromazine for
      producing prolonged neuroleptanalgesia in wild Asian elephants. ANIMALS: Ten
      adult wild elephants (four males, six females), free-roaming in the jungles of
      the north-western province of Sri Lanka. MATERIALS AND METHODS: Ten wild
      elephants were tranquilized for attachment of radio transmitter collars from
      September to November 1997, using Large-Animal Immobilon (C-Vet Veterinary
      Products, Leyland, UK), which is a combination of etorphine (2.45 mg mL(-1)) and
      acepromazine (10 mg mL(-1)). This was injected using projectile syringes fired
      from a Cap-Chur gun (Palmer Chemical Co. Inc., Atlanta, USA). A volume of 3.3
      (2.5-4.5) mL Immobilon (6.12-11.02 mg of etorphine and 25-45 mg acepromazine) was
      injected intramuscularly after body mass estimation of individual elephants.
      RESULTS: The body condition of all darted elephants was good, and the mean
      (minimum-maximum) shoulder height was 225 (180-310) cm. The average approximate
      distance to elephants at firing was 26 (15-50) m. The average time to recumbency
      after injection was 18 (15-45) minutes. Nine out of 10 elephants remained in
      lateral recumbency (and did not require additional dosing) for a period of 42 (28
      61) minutes. The respiratory and heart rates during anaesthesia were 7 (4-10)
      breaths and 52 (40-60) beats minute(-1), respectively. An equal volume (8.15
      14.67 mg) of diprenorphine hydrochloride (Revivon, 3.26 mg mL(-1) diprenorphine;
      C-Veterinary Products, Leyland, UK) was given intravenously when the procedure
      was completed. Recovery (return to standing position) occurred in 6 (2-12)
      minutes after diprenorphine injection. Immediately afterwards, all elephants
      slowly retreated into the jungle without complications. Continuous radio tracking
      of the animals involved in this study indicated no post-operative mortality for
      several months after restraint. CONCLUSIONS/CLINICAL RELEVANCE: Etorphine
      acepromazine combinations can be used safely in healthy wild Asian elephants for
      periods of restraint lasting up to 1 hour.

PMID- 15509297
TI  - Hereditary risk factors for the development of gastric cancer in younger
      patients.
AB  - BACKGROUND: It is believed that the development of gastric cancer (GC) before the
      age of 50 has a hereditary basis. Blood group A and history of gastric cancer in
      first-degree relatives have been shown to be risk factors for GC. METHODS: In
      this case-control study, we enrolled patients with GC who were diagnosed before
      the age of 50. Patients who were diagnosed as having GC were selected. A total of
      534 cases were found; of these, 44 diagnosed before the age of 50 were included
      in the case group. For the control group, 22 males and 22 females were randomly
      selected from the remaining subjects, who had diagnoses of GC after the age of
      50. All the surviving patients and family members of the dead patients were
      interviewed about the history of cancer in the family and the age at which other
      family members developed cancer. The blood group of each subject was also
      obtained. RESULTS: forty-four cases under 50 years old (mean age: 36.2 years) and
      forty-four controls (mean age: 67.1 years) were enrolled in the study. At the
      time of the study, 59.1% of the study group and 50% of the control group were
      alive (P value = NS). In the study group, 68.1%, 13.6%, 13.6% and 4.5% had blood
      groups O, A, B and AB, respectively. In the control group the corresponding
      figures were 27.7%, 63.6%, 6.8% and 4.5%. First or second-degree relatives with
      cancer, including gastric (the most frequent), breast, lung, gynecological and
      hematological malignancies, were noted in 54.5% of the cases and 11.4% of the
      controls (p < 0.01). Family histories of cancer were accepted as valid provided
      that they were based on valid medical documents. CONCLUSIONS: It seems that the
      development of GC before the age of 50 is likely to be accompanied by familial
      susceptibility. Interestingly, our study showed a significant correlation between
      blood group O and the development of gastric cancer under the age of 50.

PMID- 15509298
TI  - Effect of Ampicillin on the kinetics of colonization of Streptococcus pneumoniae
      and Lactobacillus fermentum in the respiratory tract of mice.
AB  - Ampicillin was selected to further study the effect of this antibiotic on the
      colonization capability of S. pneumoniae and L. fermentum intranasally inoculated
      in a mice experimental model. The sensitivity of S. pneumoniae and L. fermentum
      to antibiotics was evaluated by different "in vitro" techniques. The results
      showed that both microorganisms have a typical pattern of sensitivity to
      antibiotics in these assays. The "in vivo" experiments showed that the treatment
      with Ampicillin increased the number of lactobacilli and neumococci in the groups
      of mice treated only with one of the microorganisms. In those mice treated with
      Lactobacillus, challenged later with neumococci and treated with Ampicillin, the
      pathogen in lung decreased on the 4th day, disappearing completely after on. The
      histological studies showed that the antibiotic treatment decreased the
      inflammatory response produced by the pathogen at the lung and trachea levels.

PMID- 15509299
TI  - Hospitalization for heart disease, stroke, and diabetes mellitus among Indian
      born persons: a small area analysis.
AB  - BACKGROUND: We set out to describe the risk of hospitalization from heart
      disease, stroke, and diabetes among persons born in India, all foreign-born
      persons, and U.S.-born persons residing in New York City. METHODS: We examined
      billing records of 1,083,817 persons hospitalized in New York City during the
      year 2000. The zip code of each patient's residence was linked to corresponding
      data from the 2000 U.S. Census to obtain covariates not present in the billing
      records. Using logistic models, we evaluated the risk of hospitalization for
      heart disease, stroke and diabetes by country of origin. RESULTS: After
      controlling for covariates, Indian-born persons are at similar risk of
      hospitalization for heart disease (RR = 1.02, 95% confidence interval 1.02,
      1.03), stroke (RR = 1.00, 95% confidence interval, 0.99, 1.01), and diabetes
      mellitus (RR = 0.96 95% confidence interval 0.94, 0.97) as native-born persons.
      However, Indian-born persons are more likely to be hospitalized for these
      diseases than other foreign-born persons. For instance, the risk of
      hospitalization for heart disease among foreign-born persons is 0.70 (95%
      confidence interval 0.67, 0.72) and the risk of hospitalization for diabetes is
      0.39 (95% confidence interval 0.37, 0.42) relative to native-born persons.
      CONCLUSIONS: South Asians have considerably lower rates of hospitalization in New
      York than reported in countries with national health systems. Access may play a
      role. Clinicians working in immigrant settings should nonetheless maintain a
      higher vigilance for these conditions among Indian-born persons than among other
      foreign-born populations.

PMID- 15509301
TI  - Detecting spatiotemporal clusters of accidental poisoning mortality among Texas
      counties, U.S., 1980 - 2001.
AB  - BACKGROUND: Accidental poisoning is one of the leading causes of injury in the
      United States, second only to motor vehicle accidents. According to the Centers
      for Disease Control and Prevention, the rates of accidental poisoning mortality
      have been increasing in the past fourteen years nationally. In Texas, mortality
      rates from accidental poisoning have mirrored national trends, increasing
      linearly from 1981 to 2001. The purpose of this study was to determine if there
      are spatiotemporal clusters of accidental poisoning mortality among Texas
      counties, and if so, whether there are variations in clustering and risk
      according to gender and race/ethnicity. The Spatial Scan Statistic in combination
      with GIS software was used to identify potential clusters between 1980 and 2001
      among Texas counties, and Poisson regression was used to evaluate risk
      differences. RESULTS: Several significant (p < 0.05) accidental poisoning
      mortality clusters were identified in different regions of Texas. The geographic
      and temporal persistence of clusters was found to vary by racial group, gender,
      and race/gender combinations, and most of the clusters persisted into the present
      decade. Poisson regression revealed significant differences in risk according to
      race and gender. The Black population was found to be at greatest risk of
      accidental poisoning mortality relative to other race/ethnic groups (Relative
      Risk (RR) = 1.25, 95% Confidence Interval (CI) = 1.24 - 1.27), and the male
      population was found to be at elevated risk (RR = 2.47, 95% CI = 2.45 - 2.50)
      when the female population was used as a reference. CONCLUSION: The findings of
      the present study provide evidence for the existence of accidental poisoning
      mortality clusters in Texas, demonstrate the persistence of these clusters into
      the present decade, and show the spatiotemporal variations in risk and clustering
      of accidental poisoning deaths by gender and race/ethnicity. By quantifying
      disparities in accidental poisoning mortality by place, time and person, this
      study demonstrates the utility of the spatial scan statistic combined with GIS
      and regression methods in identifying priority areas for public health planning
      and resource allocation.

PMID- 15509300
TI  - Add-on therapy options in asthma not adequately controlled by inhaled
      corticosteroids: a comprehensive review.
AB  - Many patients with persistent asthma can be controlled with inhaled
      corticosteroids (ICS). However, a considerable proportion of patients remain
      symptomatic, despite the use of ICS. We present systematically evidence that
      supports the different treatment options. A literature search was made of
      Medline/PubMed to identify randomised and blinded trials. To demonstrate the
      benefit that can be obtained by increasing the dose of ICS, dose-response studies
      with at least three different ICS doses were identified. To demonstrate whether
      more benefit can be obtained by adding long-acting beta2-agonist (LABA),
      leukotriene antagonist (LTRA) or theophylline than by increasing the dose of ICS,
      studies comparing these options were identified. Thirdly, studies comparing the
      different "add-on" options were identified. The addition of a LABA is more
      effective than increasing the dose of ICS in improving asthma control. By
      increasing the dose of ICS, clinical improvement is likely to be of small
      magnitude. Addition of a LTRA or theophylline to the treatment regimen appears to
      be equivalent to doubling the dose of ICS. Addition of a LABA seems to be
      superior to an LTRA in improving lung function. However, addition of LABA and
      LTRA may be equal with respect to asthma exacerbations. However, more and longer
      studies are needed to better clarify the role of LTRAs and theophylline as add-on
      therapies.

PMID- 15509302
TI  - A comparison of vas occlusion techniques: cautery more effective than ligation
      and excision with fascial interposition.
AB  - BACKGROUND: Vasectomy techniques have been the subject of relatively few rigorous
      studies. The objective of this analysis was to compare the effectiveness of two
      techniques for vas occlusion: intraluminal cautery versus ligation and excision
      with fascial interposition. More specifically, we aimed to compare early failure
      rates, sperm concentrations, and time to success between the two techniques.
      METHODS: We compared semen analysis data from men following vasectomy using two
      occlusion techniques. Data on intraluminal cautery came from a prospective
      observational study conducted at four sites. Data on ligation and excision with
      fascial interposition came from a multicenter randomized controlled trial that
      evaluated the efficacy of ligation and excision with versus without fascial
      interposition. The surgical techniques used in the fascial interposition study
      were standardized. The surgeons in the cautery study used their customary
      techniques, which varied among sites in terms of type of cautery, use of fascial
      interposition, excision of a short segment of the vas, and use of an open-ended
      technique. Men in both studies had semen analyses two weeks after vasectomy and
      then approximately every four weeks. The two outcome measures for the analyses
      presented here are (a) time to success, defined as severe oligozoospermia, or
      <100,000 sperm/mL in two consecutive semen analyses; and (b) early vasectomy
      failure, defined as >10 million sperm/mL at week 12 or later. RESULTS: Vasectomy
      with cautery was associated with a significantly more rapid progression to severe
      oligozoospermia and with significantly fewer early failures (1% versus 5%).
      CONCLUSION: The use of cautery improves vasectomy outcomes. Limitations of this
      comparison include (a) the variety of surgical techniques in the cautery study
      and differences in methods of fascial interposition between the two studies, (b)
      the uncertain correlation between sperm concentrations after vasectomy and the
      risk of pregnancy, and (c) the use of historical controls and different study
      sites.

PMID- 15509303
TI  - In vivo gene targeting of IL-3 into immature hematopoietic cells through CD117
      receptor mediated antibody gene delivery.
AB  - BACKGROUND: Targeted gene transfection remains a crucial issue to permit the real
      development of genetic therapy. As such, in vivo targeted transfection of
      specific subsets of hematopoietic stem cells might help to sustain hematopoietic
      recovery from bone marrow aplasia by providing local production of growth
      factors. METHODS: Balb/C mice were injected intravenously, with an anti-mouse c
      kit (CD117) monoclonal antibody chemically coupled to a human IL-3 gene
      containing plasmid DNA. Mice were sacrificed for tissue analyses at various days
      after injection of the conjugates. RESULTS: By ELISA, the production of human IL
      3 was evidenced in the sera of animals 5 days after treatment. Cytofluorometric
      analysis after in vivo transfection of a reporter gene eGFP demonstrated
      transfection of CD117+/Sca1+ hematopoietic immature cells. By PCR analysis of
      genomic DNA and RNA using primer specific pIL3 sequences, presence and expression
      of the human IL-3-transgene were detected in the bone marrow up to 10 days in
      transfected mice but not in control animals. CONCLUSIONS: These data clearly
      indicate that antibody-mediated endocytosis gene transfer allows the expression
      of the IL-3 transgene into hematopoietic immature cells, in vivo. While
      availability of marketed recombinant growth factors is restricted, this targeting
      strategy should permit delivery of therapeutic genes to tissues of interest
      through systemic delivery. In particular, the ability to specifically target
      growth factor expression into repopulating hematopoietic stem cells may create
      new opportunities for the treatment of primary or radiation-induced marrow
      failures.

PMID- 15509304
TI  - An evaluation of UV protection imparted by cotton fabrics dyed with natural
      colorants.
AB  - BACKGROUND: The ultraviolet properties of textiles dyed with synthetic dyes have
      been widely reported in literature. However, no study has investigated the
      ultraviolet properties of natural fabrics dyed with natural colorants. This study
      reports the Ultraviolet Protection Factor (UPF) of cotton fabrics dyed with
      colorants of plant and insect origins. METHODS: Three cotton fabrics were dyed
      with three natural colorants. Fabrics were characterized with respect to fabric
      construction, weight, thickness and thread count. Influence of fabric
      characteristics on Ultraviolet Protection Factor was studied. Role of colorant
      concentration on the ultraviolet protection factor was examined via color
      strength analysis. RESULTS: A positive correlation was observed between the
      weight of the fabric and their UPF values. Similarly, thicker fabrics offered
      more protection from ultraviolet rays. Thread count appears to negatively
      correlate with UPF. Dyeing with natural colorants dramatically increased the
      protective abilities of all three fabric constructions. Additionally, within the
      same fabric type UPF values increased with higher depths of shade. CONCLUSION:
      Dyeing cotton fabrics with natural colorants increases the ultraviolet protective
      abilities of the fabrics and can be considered as an effective protection against
      ultraviolet rays. The UPF is further enhanced with colorant of dark hues and with
      high concentration of the colorant in the fabric.

PMID- 15509305
TI  - Dual practice in the health sector: review of the evidence.
AB  - This paper reports on income generation practices among civil servants in the
      health sector, with a particular emphasis on dual practice. It first approaches
      the subject of public-private overlap. Thereafter it focuses on coping strategies
      in general and then on dual practice in particular.To compensate for
      unrealistically low salaries, health workers rely on individual coping
      strategies. Many clinicians combine salaried, public-sector clinical work with a
      fee-for-service private clientele. This dual practice is often a means by which
      health workers try to meet their survival needs, reflecting the inability of
      health ministries to ensure adequate salaries and working conditions.Dual
      practice may be considered present in most countries, if not all. Nevertheless,
      there is surprisingly little hard evidence about the extent to which health
      workers resort to dual practice, about the balance of economic and other motives
      for doing so, or about the consequences for the proper use of the scarce public
      resources dedicated to health.In this paper dual practice is approached from six
      different perspectives: (1) conceptual, regarding what is meant by dual practice;
      (2) descriptive, trying to develop a typology of dual practices; (3)
      quantitative, trying to determine its prevalence; (4) impact on personal income,
      the health care system and health status; (5) qualitative, looking at the reasons
      why practitioners so frequently remain in public practice while also working in
      the private sector and at contextual, personal life, institutional and
      professional factors that make it easier or more difficult to have dual
      practices; and (6) possible interventions to deal with dual practice.

PMID- 15509306
TI  - Long-term age-dependent behavioral changes following a single episode of fetal N
      methyl-D-Aspartate (NMDA) receptor blockade.
AB  - BACKGROUND: Administration of the N-methyl-D-aspartate (NMDA) antagonist ketamine
      during the perinatal period can produce a variety of behavioral and
      neuroanatomical changes. Our laboratory has reported reliable changes in learning
      and memory following a single dose of ketamine administered late in gestation.
      However, the nature of the drug-induced changes depends on the point during
      embryonic development when ketamine is administered. Embryonic day 18 (E18) rat
      fetuses pre-treated with ketamine (100 mg/kg, i.p. through the maternal
      circulation) and taught a conditioned taste aversion (CTA) learn and remember the
      CTA, whereas E19 fetuses do not. The current study sought to determine if long
      term behavioral effects could be detected in animals that received ketamine or a
      saline control injection on either E18 or E19. Rat behavior was evaluated on two
      different measures: spontaneous locomotion and water maze learning. Measurements
      were collected during 2 periods: Juvenile test period [pre-pubertal locomotor
      test: Postnatal Day 11 (P11); pre-pubertal water maze test: P18] or Young-adult
      test period [post-pubertal locomotor test: P60; post-pubertal water maze test:
      P81]. RESULTS: Water maze performance of ketamine-treated rats was similar to
      that of controls when tested on P18. Likewise, the age of the animal at the time
      of ketamine/saline treatment did not influence learning of the maze. However, the
      young-adult water maze test (P81) revealed reliable benefits of prenatal ketamine
      exposure - especially during the initial re-training trial. On the first trial of
      the young adult test, rats treated with ketamine on E18 reached the hidden
      platform faster than any other group - including rats treated with ketamine on
      E19. Swim speeds of experimental and control rats were not significantly
      different. Spontaneous horizontal locomotion measured during juvenile testing
      indicated that ketamine-treated rats were less active than controls. However,
      later in development, rats treated with ketamine on E18 were more active than
      rats that received the drug on E19. CONCLUSION: These data suggest that both the
      day in fetal development when ketamine is administered and the timing of post
      natal behavioral testing interact to influence behavioral outcomes. The data also
      indicate that the paradoxical age-dependent effects of early ketamine treatment
      on learning, previously described in fetuses and neonates, may also be detected
      later in young adult rats.

PMID- 15509307
TI  - Improvement of alignment accuracy utilizing sequentially conserved motifs.
AB  - BACKGROUND: Multiple sequence alignment algorithms are very important tools in
      molecular biology today. Accurate alignment of proteins is central to several
      areas such as homology modelling, docking studies, understanding evolutionary
      trends and study of structure-function relationships. In recent times,
      improvement of existing progressing programs and implementation of new iterative
      algorithms have made a significant change in this field. RESULTS: We report an
      alignment algorithm that combines progressive dynamic algorithm, local
      substructure alignment and iterative refinement to achieve an improved, user
      interactive tool. Large-scale benchmarking studies show that this FMALIGN server
      produces alignments that, aside from preservation of functional and structural
      conservation, have accuracy comparable to other popular multiple alignment
      programs. CONCLUSIONS: The FMALIGN server allows the user to fix conserved
      regions in equivalent position in the alignment thereby reducing the chance of
      global misalignment to a great extent. FMALIGN is available at
      http://caps.ncbs.res.in/FMALIGN/Home.html.

PMID- 15509308
TI  - Routine cerebral angiography after surgery for saccular aneurysms: is it worth
      it?
AB  - OBJECTIVE: The objective of this study was to determine whether an
      angiographically proven rate of saccular intracranial aneurysm occlusion after
      surgical clipping suggests that postoperative angiography should continue to be
      used routinely or should be supplanted by intraoperative angiography. These data
      also should establish a basis for comparing surgery with new endovascular methods
      of treatment. METHODS: During a 3.5-year period, a consecutive series of 622
      patients (955 aneurysms, 808 of which were surgically clipped) who underwent
      postoperative angiography were studied retrospectively. This series comprised 493
      ruptured and 315 unruptured aneurysms. RESULTS: Complete aneurysm closure was
      achieved in 88% of aneurysms, a neck remnant was discovered in 9%, and a fundus
      remnant was revealed in 3%. Of 493 ruptured aneurysms, 86% were completely
      occluded. Of 315 unruptured aneurysms, 91% were completely occluded. The results
      for clipping of complex aneurysms, i.e., posterior circulation or large to giant
      aneurysms, were significantly inferior to those for small and anterior
      circulation aneurysms. In one-third of the large and giant aneurysms, a part of
      the base was left intentionally because of calcifications or strong wall or to
      prevent occlusion of any branches. In the series, a significant 5% complication
      rate of major vessel occlusion was detected. CONCLUSION: Our retrospective
      analysis revealed that ruptured, posterior circulation, and large/giant aneurysms
      are more prone to incomplete clipping. Therefore, these aneurysms require
      postoperative if not intraoperative evaluation with angiography. Many clippings
      of anterior circulation aneurysms experience unexpected failures, which suggests
      that intraoperative angiography could be beneficial. This series, which has no
      selection bias, can be used as a basis to compare the results of other series
      reporting surgical or endovascular treatment.

PMID- 15509309
TI  - Anteroinferior cerebellar artery aneurysms: surgical approaches and outcomes--a
      review of 34 cases.
AB  - OBJECTIVE: Anteroinferior cerebellar artery (AICA) aneurysms are rare lesions
      whose treatment requires expertise in vascular, endovascular, and cranial base
      surgery. This article presents the largest series treated at one center. METHODS:
      We retrospectively analyzed presenting symptoms, aneurysm characteristics,
      surgical approaches, postoperative outcomes, and the application of endovascular
      techniques. RESULTS: We found 32 patients with 34 AICA aneurysms (11 men and 21
      women; age range, 6-77 yr; mean age, 51 yr). Twenty-one aneurysms had ruptured;
      13 were unruptured. Seven of the unruptured aneurysms presented with brainstem
      compression, and six were found incidentally. Surgical approaches included the
      retrosigmoid, far-lateral transcochlear, translabyrinthine, and orbitozygomatic.
      Eighteen patients (56%) had neurological complications. Thirty aneurysms were at
      proximal locations, and four were distal. Intraoperative hypothermic cardiac
      arrest was used to clip eight giant aneurysms. Follow-up was available in 56% of
      the patients for a mean of 41 months. The mean Glasgow Outcome Scale scores at
      discharge were not significantly different from the patients' status at their
      initial assessment. CONCLUSION: We recommend the standard retrosigmoid approach
      for treating small to medium aneurysms involving the lower two-thirds of the
      clivus or distal AICA aneurysms. Cranial base approaches are recommended for
      large or giant aneurysms or for those proximal to the emergence of the AICA from
      the basilar trunk. Hypothermic cardiac arrest facilitates dissection of giant
      aneurysms. Endovascular treatment is a useful adjunct for treating residual
      aneurysms but did not provide definitive treatment in any of our patients.

PMID- 15509310
TI  - Bypass grafting and revascularization in the management of posterior circulation
      aneurysms.
AB  - OBJECTIVE: To describe the bypass techniques, cranial base approaches, results of
      treatment, causes of failure, and lessons that are learned in patients with
      posterior circulation aneurysms requiring revascularization. METHODS:
      Retrospectively, 19 patients with posterior fossa aneurysms requiring
      revascularization procedures operated on between 1991 and 2002 were reviewed.
      Preoperative and postoperative clinical information, neurological examinations,
      imaging data, and updated follow-ups were reviewed. Patient outcome is reported
      as the most current Karnofsky Performance Scale score. RESULTS: A total of 22
      arterial bypasses were performed in 19 patients for posterior fossa circulation
      aneurysms between 1991 and 2002. The mean follow-up was 41 months. Total graft
      patency rate (including patients requiring reoperation) was 86.4% (before) and
      100% (after) salvage procedures. Patient outcome was 84.2% with Karnofsky
      Performance Scale score 80 to 90, and three deaths occurred perioperatively. Only
      one death could be attributed to the failure of the radial artery graft because
      of spasm and subsequent rupture during angioplasty. CONCLUSION: Certain graft
      selection criteria and technical considerations contribute to the success or
      failure of bypass grafts in the management of posterior circulation aneurysms.
      Bypass procedures remain an important method of management of complex posterior
      circulation aneurysms, in addition to endovascular procedures.

PMID- 15509311
TI  - Fenestration of the lamina terminalis as a valuable adjunct in aneurysm surgery.
AB  - OBJECTIVE: Hydrocephalus, vasospasm, and frontobasal injury are common
      complications after aneurysmal subarachnoid hemorrhage (SAH) from anterior
      communicating artery aneurysms. Previous studies have suggested that fenestration
      of the lamina terminalis (FLT) during surgery may be associated with reduced
      rates of shunt-dependent hydrocephalus and vasospasm. We report 106 patients
      affected by anterior communicating artery aneurysms and Fisher Grade 3 aneurysmal
      SAH and the affect of FLT on shunt-dependent hydrocephalus, vasospasm, and
      frontobasal injury. METHODS: During a 3-year period, 53 patients underwent FLT
      and 53 did not. We prospectively evaluated admission and discharge clinical
      grades, hydrocephalus at admission, occurrence of clinical vasospasm, need for
      interventional vasospasm therapy, frontobasal hypodensity incidence, and
      permanent ventriculoperitoneal shunting requirement. Follow-up ranged from 3 to
      35 months (mean, 17.9 mo). RESULTS: Shunting incidence after aneurysmal SAH with
      hydrocephalus was 4.25% in patients who underwent FLT and 13.9% in patients who
      did not (P < 0.001). Clinical cerebral vasospasm occurred in 29.6% of patients
      who underwent FLT and in 54.7% of patients who did not (P < 0.001). Frontobasal
      hypodensity was identified postoperatively in 0% of patients who underwent FLT
      and in 5% of patients who did not. Good outcome was reported in 69.81% of
      patients who underwent FLT and in 33.96% of patients who did not (P < 0.001).
      Poor outcome was associated with higher Hunt and Hess grades, need for
      ventricular drainage, elevated intracranial pressure, and multiple interventional
      vasospasm therapies. No complications were linked to FLT. CONCLUSION: FLT was
      associated with statistically significant decreases in shunting rates, incidence
      of vasospasm, and better outcomes. We recommend its routine use in patients with
      Fisher Grade 3 anterior communicating artery aneurysmal SAH.

PMID- 15509312
TI  - Pretreatment with the free radical scavenger edaravone prevents cerebral
      hyperperfusion after carotid endarterectomy.
AB  - OBJECTIVE: Cerebral hyperperfusion syndrome after carotid endarterectomy (CEA) is
      a rare but potentially devastating complication. The purpose of the present
      study, which was not a randomized controlled trial but a case cohort study with
      historical control, was to determine whether pretreatment with a novel free
      radical scavenger, edaravone, could prevent occurrence of cerebral hyperperfusion
      after CEA. METHODS: Fifty patients with ipsilateral internal carotid artery
      stenosis (>/=70%) underwent CEA with administration of edaravone before internal
      carotid artery clamping. Preoperative cerebral blood flow and cerebrovascular
      reactivity (CVR) to acetazolamide were assessed with single-photon emission
      computed tomography (SPECT). Cerebral blood flow also was measured immediately
      after CEA and on the 3rd postoperative day. RESULTS: Cerebral hyperperfusion
      (cerebral blood flow increase >/=100% compared with preoperative values) was
      revealed by SPECT performed immediately after CEA in only one patient (2%), who
      also exhibited reduced preoperative CVR. The incidence of post-CEA hyperperfusion
      as revealed by SPECT in the control group (51 CEA patients without administration
      of edaravone) was significantly higher (16%) (P = 0.0310, control versus
      treatment group). In addition, in a subgroup of patients with reduced
      preoperative CVR, the incidence of post-CEA hyperperfusion as revealed by SPECT
      in the edaravone group (7%) was significantly lower than that in the control
      group (67%) (P = 0.0029). Logistic regression analysis demonstrated that reduced
      preoperative CVR and absence of pretreatment with edaravone were significant
      independent predictors of post-CEA hyperperfusion as revealed by SPECT.
      CONCLUSION: Pretreatment with edaravone can prevent occurrence of cerebral
      hyperperfusion after CEA.

PMID- 15509313
TI  - Proposed treatment strategy for cavernous sinus meningiomas: a prospective study.
AB  - OBJECTIVE: To establish a safe and effective treatment strategy for cavernous
      sinus (CS) meningiomas, we prospectively analyzed the outcome of a treatment
      protocol combining surgery and radiosurgery during the past 7 years. METHODS:
      Tumors confined to the CS and distant from the optic apparatus and the brainstem
      were treated with radiosurgery alone. Tumors attached to or compressing the optic
      apparatus and brainstem and that were larger than 3 cm in mean diameter, extended
      into the multiple cranial fossae, and were suspected of being malignant were
      treated with combined nonradical microsurgery and radiosurgery. RESULTS: In
      accordance with this treatment protocol, 40 patients aged 26 to 72 years (median,
      51 yr) with primary (n = 27) or recurrent (n = 13) CS meningiomas (volume range,
      0.9-39.3 cm(3); median volume, 5.4 cm(3)) were treated with combined surgery and
      radiosurgery (n = 23) or radiosurgery alone (n = 17). During radiosurgery, 12 to
      18 Gy (median, 16 Gy) was delivered to the tumor margin. The follow-up period
      ranged from 14 to 79 months (median, 47 mo). The actuarial tumor control rate was
      94.1% at 5 years. The improvement of cranial nerve function was significantly
      frequent in patients with primary CS meningiomas (P < 0.05). Permanent cranial
      nerve dysfunction was significantly frequent in patients with tumors compressing
      the brainstem or smaller than 10 cm(3) (P < 0.05). All 36 patients with a
      pretreatment Karnofsky Performance Scale score of 90 or more maintained the same
      range after treatment. CONCLUSION: Proper combination of microsurgery and
      radiosurgery for CS meningiomas provides excellent growth control with favorable
      functional state. Outcomes were better when this protocol was adopted at the
      initial diagnosis for patients with smaller tumors that did not compress the
      brainstem.

PMID- 15509314
TI  - Linear accelerator radiosurgery in the treatment of brain metastases.
AB  - OBJECTIVE: To review a 12-year experience treating metastatic brain disease with
      linear accelerator-based stereotactic radiosurgery (SRS). METHODS: We performed a
      retrospective analysis of all patients treated between 1989 and 2001 with linear
      accelerator radiosurgery for brain metastases. Patients were followed up both
      clinically and with imaging studies to document local control, regional control,
      and survival. Demographic data, dosing parameters, number of lesions, histology,
      history of whole-brain radiation therapy, and other factors were obtained
      prospectively. Cox proportional-hazards regression with multivariate and
      univariate analysis was performed with Stata 8.0 software. RESULTS: A total of
      383 patients received SRS for brain metastases during the study interval. Median
      survival was 9 months. Patients with tumor-type melanoma or multiple metastatic
      lesions had decreased survival. Actuarial 1-year local control was 75%.
      Differences in regional control rates were not statistically significant between
      patients treated with SRS and whole-brain radiation therapy versus SRS alone.
      CONCLUSION: Radiosurgery is an effective and safe method for treating selected
      patients with brain metastases.

PMID- 15509315
TI  - Vagus nerve stimulation therapy after failed cranial surgery for intractable
      epilepsy: results from the vagus nerve stimulation therapy patient outcome
      registry.
AB  - OBJECTIVE: To determine the effectiveness of vagus nerve stimulation (VNS)
      therapy among patients with persistent or recurrent seizures after lobar
      resection, callosotomy, and other cranial operations for intractable epilepsy.
      METHODS: Data were obtained from the VNS therapy patient outcome registry, which
      was established after United States Food and Drug Administration approval of the
      VNS device in 1997 as a means of capturing open-label clinical data outside of
      protocol. The integrity of the systems for collecting and processing registry
      data was authenticated by an independent auditing agency. The effect of potential
      selection bias, however, remains uncertain. RESULTS: Two nonconsecutive cohorts
      were compared: patients tracked in the registry who had previously undergone
      cranial surgery for epilepsy (CS group, n = 921) and those who had not (non-CS
      group, n = 3822). For the CS group, the median reduction in seizure frequency was
      42.5% after 3 months of VNS therapy, 42.9% at 6 months, 45.7% at 12 months, 52.0%
      at 18 months, and 50.5% at 24 months. For the non-CS group, analogous rates were
      47.0%, 52.9%, 60.0%, 62.7%, and 66.7%, respectively. In the CS group, seizures
      were reduced by at least 50% in 55.1% of patients, at least 75% in 31.4% of
      patients, at least 90% in 17.3% of patients, and 100% in 5.1% of patients after
      24 months of VNS therapy. Response rates were more pronounced in the non-CS
      group: at least 50% in 62.2% of patients, at least 75% in 43.7% of patients, at
      least 90% in 26.8% of patients, and 100% in 8.3% of patients. Patients in both
      groups experienced marked improvements in quality of life parameters. CONCLUSION:
      The effectiveness of VNS is maintained during prolonged stimulation, and overall
      seizure control continues to improve with time. Patients in whom prior cranial
      surgery had failed did not respond as favorably as all other patients receiving
      VNS therapy. Nonetheless, many of the former group improved substantially. Thus,
      on the basis of these open-label data, VNS therapy represents a potentially
      palliative treatment option for patients with refractory seizures after failed
      cranial surgery.

PMID- 15509316
TI  - Pseudotumor cerebri patients with shunts from the cisterna magna: clinical course
      and telemetric intracranial pressure data.
AB  - OBJECTIVE: Shunting of cerebrospinal fluid (CSF) to an extracranial site is the
      mainstay of treatment of absorptive hydrocephalus and pseudotumor cerebri. On
      occasion, both lateral ventricles and the lumbar space become unsuitable for
      placement of a functioning CSF drainage catheter. We have encountered several
      such patients and describe our strategy of shunting from the cisterna magna to
      the pleural space or cardiac atrium. METHODS: We report a retrospective review of
      the clinical course of five patients with cisternal shunts and intracranial
      pressure telemonitoring devices. RESULTS: Cisternal shunting was able to
      successfully drain CSF to a normal pressure in all five patients. CSF pressure
      data collected from those patients indicate that the CSF pressure dynamics in
      cisternal shunts is similar to that of ventricular shunts. However, the cisternal
      shunting and subsequent high revision rate did result in a significant number of
      complications and two shunt infections. CONCLUSION: Shunting CSF from the
      cisterna magna in the absence of another suitable drainage site does result in
      acceptable reduction of elevated intracranial pressure. However, the technique is
      associated with a high complication rate that may reflect the population of
      patients in whom this technique is required.

PMID- 15509317
TI  - Concussion in professional football: injuries involving 7 or more days out--Part
      5.
AB  - OBJECTIVE: A 6-year study was conducted to determine the signs, symptoms, and
      outcome of concussions with 7 or more (7+) days out from play or extended
      postconcussion recovery in the National Football League (NFL). METHODS: From 1996
      to 2001, reporting of concussion was performed by NFL teams using a special
      standardized reporting form filled out by team physicians. Signs and symptoms
      were grouped by general symptoms, somatic complaints, cranial nerve effects,
      cognition problems, memory problems, and unconsciousness. Medical action taken
      and management were recorded. In all, 887 concussions were reported in practices
      and games. RESULTS: There were 72 concussions (8.1%) involving 7+ days out from
      play. The highest frequency occurred in quarterbacks (14.8%), the return unit on
      special teams (11.8%), and secondary (10.8%). Quarterbacks had the highest odds
      ratio (OR) of 7+ days out with concussion (OR = 2.10, P = 0.049), whereas running
      backs had the lowest relative risk (OR = 0.13, P = 0.021). The greatest fraction
      of 7+ days out occurred in passing plays (36.1%) and kickoffs (22.2%). Many signs
      and symptoms occurred at a greater frequency on initial examination in players 7+
      days out; the average number per player was 4.64 with 7+ days out versus 2.58
      with fewer days out (t = 6.02, df = 77.1). The signs and symptoms with the
      highest incidence for 7+ days out were disorientation to time (chi(2) = 51.2, P =
      001), retrograde amnesia (chi(2) = 33.2, P = 0.001), fatigue (chi(2) = 28.1, P =
      0.001), and the general category of cognition problems (chi(2) = 21.7, P =
      0.001). Loss of consciousness for more than 1 minute was a predictor of 7+ days
      out (chi(2) = 33.5, P = 0.001), although it occurred in only 7.9% of cases. Of
      players with 7+ days out, 72.2% were removed from the game and 12.5% were
      hospitalized. These frequencies were significantly greater than for players with
      fewer than 7 days out (chi(2) = 68.03, df = 3, P < 0.0001). Approximately 90% of
      players were managed by rest, irrespective of days out, but a greater fraction
      were given drug or medical therapies with prolonged days out. CONCLUSION: The
      most vulnerable players for 7+ days out with concussion were quarterbacks and the
      secondary in professional football. Although 8.1% of concussions involved 7+ days
      out, only 1.6% involved a prolonged postconcussion syndrome. They recovered from
      symptoms and had a consistent return to play in the NFL.

PMID- 15509318
TI  - Missile-caused ulnar nerve injuries: outcomes of 128 repairs.
AB  - OBJECTIVE: This prospective study presents repair results after missile-caused
      ulnar nerve ruptures as well as factors influencing the outcomes. METHODS:
      Between 1991 and 1994, 128 casualties with missile-caused complete ulnar nerve
      injury were managed surgically in the Neurosurgical Department of the Belgrade
      Military Medical Academy. At least 4 years after surgery, we scored sensorimotor
      recovery, neurophysiological recovery, and patient judgment of the outcome. On
      the basis of the total score, we defined the final outcome as poor, insufficient,
      good, or excellent. The last two outcomes were considered to be successful.
      RESULTS: A successful outcome was obtained in 0% of high-level, 33.8% of
      intermediate-level, and 77.3% of low-level repairs (P < 0.001). On average, the
      nerve defect, preoperative interval, and patient age were lower for patients with
      a successful outcome than for those with an unsuccessful outcome (P = 0.004, P =
      0.032, and P = 0.003, respectively). Worsening of the outcome was related to
      nerve defect longer than 4.5 cm, preoperative interval longer than 5.5 months,
      and age older than 23 years (P = 0.002, P = 0.034, and P = 0.023, respectively).
      A successful outcome occurred in 48.8% of patients repaired with direct suture
      and in 41.2% of patients repaired with a nerve graft (P > 0.05). A successful
      outcome also occurred 22.2% of combined ulnar-median nerve repairs and in 49.5%
      of isolated ulnar nerve repairs (P = 0.011). Repair level (P < 0.001),
      preoperative interval (P = 0.001), length of the nerve defect (P < 0.001), and
      associated median nerve rupture (P = 0.028) were independent predictors of a
      successful outcome. CONCLUSION: The outcome of ulnar nerve repair depends
      significantly on the repair level, preoperative interval, associated median nerve
      injury, length of the nerve defect, and age of the patient. High-level ulnar
      nerve repair is probably useless if performed in the classic manner.

PMID- 15509319
TI  - Spastic equinus foot: multicenter study of the long-term results of tibial
      neurotomy.
AB  - OBJECTIVE: Tibial neurotomy is a surgical technique widely used for the treatment
      of spastic equinus foot, but it has rarely been evaluated. The primary objective
      of this prospective study was to provide an objective quantification of the long
      term results of tibial neurotomy. METHODS: This multicenter prospective study was
      conducted from 1999 to 2003. Fifty-five patients with spastic equinus foot were
      treated in five neurosurgical centers. Preoperative and postoperative clinical
      evaluation comprised description of the foot deformity, study of stretch
      reflexes, evaluation of the repercussions of the deformity, and gait analysis.
      Selective neurotomy was performed in all patients. RESULTS: No postoperative
      complications were observed. The mean postoperative follow-up was 10 months.
      Tibial neurotomy improved the appearance of the foot (equinus and varus
      deformities, claw toes); the equinus score decreased from 1.54 to 0.273 after the
      operation. Stretch reflex scores were decreased significantly and for a long term
      after surgery; the mean triceps surae stretch reflex score decreased from 2.46 to
      0.47. The angle of passive dorsiflexion of the ankle increased significantly
      (from -0.56 degrees to +6.85 degrees). Gait analysis demonstrated a statistically
      significant increase in the speed of the patient's gait after surgical treatment;
      the time taken by the patient to walk 10 m at a normal speed in shoes decreased
      from a mean of 55 seconds to 35.16 seconds. Postoperatively, 92.7% of
      preoperative objectives had been achieved. CONCLUSION: Tibial neurotomy ensures
      long-term functional improvement of patients with spastic equinus foot. It
      provides a lasting response for these patients compared with other, more
      transient treatments.

PMID- 15509320
TI  - An anthropomorphic phantom study of the accuracy of Cyberknife spinal
      radiosurgery.
AB  - OBJECTIVE: Stereotactic radiosurgery requires the highest degree of accuracy in
      target identification and localization. When targeting paraspinal lesions, the
      CyberKnife radiosurgical system (Accuray, Inc., Sunnyvale, CA) uses implanted
      stainless steel fiducials. The purpose of this study was to evaluate the total
      system for clinically relevant accuracy of this approach. METHODS: The clinically
      relevant accuracy of the CyberKnife depends on 1) the accuracy of beam delivery,
      which in turn represents a compilation of robot and camera image-tracking errors,
      and 2) the inherent accuracy of target localization that stems from computed
      tomographic imaging and treatment planning. The clinically relevant accuracy was
      measured at three different CyberKnife facilities using head and torso phantoms
      loaded with packs of radiochromic film and expressed as a displacement of the
      dose contours from the treatment planning. RESULTS: The mean clinically relevant
      error, as measured at three different CyberKnife facilities, was determined to be
      0.7 +/- 0.3 mm, which did not vary with computed tomographic slice thickness in a
      range of 0.625 to 1.5 mm. The average treatment delivery precision was 0.3 +/-
      0.1 mm. Fiducial tracking error was less than 0.3 mm for radial translations up
      to 14 mm and less than 0.7 mm for rotations up to 4.5 degrees. CONCLUSION: For
      the treatment of relatively stationary spinal lesions targeted with fiducial
      tracking, the CyberKnife system is capable of submillimeter accuracy.

PMID- 15509321
TI  - Ulnar nerve entrapment neuropathy at the elbow: simple decompression.
AB  - Ulnar nerve entrapment neuropathy at the elbow, or the cubital tunnel syndrome,
      is frequently encountered in neurosurgical practice as the second most common
      peripheral nerve entrapment after carpal tunnel syndrome. Patients typically
      present with weakness or atrophy of the hand as well as paresthesias in the ulnar
      nerve distribution. The diagnosis can be confirmed with a careful clinical
      examination and electrophysiological studies. Patients who have failed
      conservative therapy are considered for surgery. Although a number of surgical
      options are available, simple decompression of the ulnar nerve can achieve
      satisfactory results with appropriate patient selection. We describe the relevant
      anatomy and surgical techniques for simple in situ decompression of the ulnar
      nerve at the elbow.

PMID- 15509322
TI  - Direct detection of bacterial pathogens in brain abscesses by polymerase chain
      reaction amplification and sequencing of partial 16S ribosomal deoxyribonucleic
      acid fragments.
AB  - OBJECTIVE: To evaluate the feasibility of detecting bacterial pathogens directly
      from the clinical brain abscess specimens by polymerase chain reaction (PCR)
      amplification and sequencing of bacterial 16S ribosomal deoxyribonucleic acid
      (rDNA). METHODS: A total of 14 specimens were tested by both culture and PCR
      amplification, targeting the full-length or a partial region of 16S rDNA. 16S
      rDNA is known to be conserved in bacteria. Sequencing of partial-length and full
      length 16S rDNA was performed. The sequence data were compared with known
      sequences of 16S rDNA in the National Center for Biotechnology Information
      GenBank by using the Basic Local Alignment Search Tool (BLAST) algorithm. The
      species with the best match of similarity were regarded as the pathogenic species
      in the samples. We also developed a Streptococcus-specific multiplex PCR analysis
      for identifying members of the Streptococcus species, the most common pathogen of
      brain abscesses. RESULTS: The 10 culture-positive specimens were all PCR-positive
      for partial 16S rDNA, but only seven were positive for full-length 16S rDNA
      amplification. Bacterial DNA was not detected in the remaining four specimens
      with a negative culture. Species identification by phenotypes from culture was in
      agreement with that by sequencing results of partial-length (or full-length) 16S
      rDNA. The Streptococcus-specific PCR analysis could detect Streptococcus species
      correctly in one step. CONCLUSION: Bacterial 16S rDNA sequences provide reliable
      clues to the identification of unknown pathogens. PCR analysis of 16S rDNA and
      sequencing may identify pathogens to the species level directly from brain
      abscesses. This approach is rapid and is useful especially in the identification
      of slow-growing and fastidious organisms.

PMID- 15509323
TI  - Loss of heterozygosity analysis of benign, atypical, and anaplastic meningiomas.
AB  - OBJECTIVE: Up to 70% of typical meningiomas demonstrate allelic loss at
      chromosome 22q. Allelic loss at additional chromosomal loci is associated with
      atypia and anaplasia in meningiomas. The pattern of allelic loss or loss of
      heterozygosity (LOH) follows a nonrandom, multistep pattern. METHODS: All
      surgical meningioma samples obtained from 1991 to 1992 at the University of
      Pittsburgh Medical Center were analyzed according to current World Health
      Organization criteria. Samples without constitutional deoxyribonucleic acid (DNA)
      were excluded from this analysis. Individual hematoxylin and eosin slides from 43
      patients were microdissected, and the DNA was harvested and amplified in the
      presence of 24 pairs of polymerase chain reaction primers, representing 24
      microsatellite loci. The polymerase chain reaction products were subjected to
      capillary gel electrophoresis and a fluorescence-based DNA analysis system. LOH
      was defined as ratios of allelic peak heights falling within a conservative
      threshold of less than 0.5 or more than 2.0. Fisher's exact test and receiver
      operator characteristic curves were used to test the relationship between benign
      versus atypical and malignant pathological features and LOH at specific loci or
      combinations of loci. RESULTS: On review by two independent pathologists, 34
      benign meningiomas, 6 atypical meningiomas, and 3 anaplastic meningiomas were
      identified. The mean number of alleles with LOH was 1.5 +/- 1.2 for benign
      meningiomas, 6.7 +/- 2.7 for atypical meningiomas, and 8.3 +/- 2.3 for anaplastic
      meningiomas (P < 0.001). The most important individual loci to predict malignancy
      were D1S407 (P = 0.006), L-myc (P < 0.001), D10S520 (P = 0.003), D10S1173 (P =
      0.042), D11S1920 (P < 0.001), D14S555 (P = 0.041), D17S1289 (P < 0.001), D22S417
      (P = 0.001), D22S431 (P = 0.019), and D22S532 (P = 0.028). Combining the LOH data
      across loci, the area under the receiver operator characteristic curve was 0.993,
      corresponding to virtually perfect prediction of pathological characteristics.
      CONCLUSION: Microsatellite marker analysis of allelic loss is a useful method of
      predicting atypia and anaplasia in meningiomas. More regions of allelic loss are
      seen in anaplastic and atypical meningiomas as compared with benign meningiomas.
      This study confirms previously reported chromosomal regions of allelic loss in
      atypical and anaplastic meningiomas and suggests additional chromosomal regions
      that may represent heretofore uncharacterized deletions within meningiomas. This
      type of genetic fingerprint ultimately may serve both a diagnostic and
      therapeutic role.

PMID- 15509324
TI  - Anatomy of the anterior temporal lobe and the frontotemporal region demonstrated
      by fiber dissection.
AB  - OBJECTIVE: The white matter structure of the anterior temporal lobe and the
      frontotemporal region is complex and not well appreciated from the available
      neurosurgical literature. The fiber dissection method is an excellent means of
      attaining a thorough knowledge of the three-dimensional structure of the white
      matter tracts. This study was performed to demonstrate the usefulness of the
      dissection technique in understanding the white matter anatomy and the effects of
      current surgical approaches on the subcortical structure of the region. METHODS:
      Seventeen brain specimens obtained at routine autopsy were dissected by use of
      Klingler's fiber dissection technique after preparation by fixation and freezing.
      The dissections were performed with an operating microscope and followed a
      stepwise pattern of progressive white matter dissection. RESULTS: The dissection
      is described in an orderly fashion showing the white matter tracts of the
      anterior temporal lobe and the frontotemporal region. An insight is gained into
      the three-dimensional course of the anterior loop of the optic radiation, the
      temporal stem, the anterior commissure, and the ansa peduncularis. CONCLUSION:
      The anterior temporal lobe and the frontotemporal region contain several
      important white matter tracts that can be uniquely understood by performing a
      white matter dissection of the region. Surgical procedures on the anterior
      temporal lobe differ substantially as to their repercussions on the subcortical
      white matter tract anatomy, as shown by the findings in this study.

PMID- 15509325
TI  - Marrow stromal cell transplantation after traumatic brain injury promotes
      cellular proliferation within the brain.
AB  - OBJECTIVE: This study was designed to investigate the effects of intracerebral as
      well as intravenous administration of bone marrow stromal cells (MSCs) on
      endogenous cellular proliferation after traumatic brain injury (TBI). METHODS:
      Two experimental groups of Wistar rats were studied. One group received MSCs
      intracerebrally, and the other group received MSCs intravenously after injury by
      controlled cortical impact. MSCs were harvested from the bone marrow of male
      Wistar rats. For the intracerebral study, 24 male rats were divided into three
      groups (eight rats per group): rats injected with MSCs (1 x 10(6))
      intracerebrally 1 day after TBI; 2) rats injected with phosphate-buffered saline
      intracerebrally 1 day after TBI; and 3) sham group not subjected to injury and
      not administered treatment. For the intravenous study, 10 female Wistar rats were
      injected 1 day after TBI with either MSCs (2 x 10(6)) (n = 5) or phosphate
      buffered saline (n = 5) via the tail vein. Neurological function of the rats was
      evaluated with modified neurological severity scores and rotarod motor test. All
      rats were injected with bromodeoxyuridine intraperitoneally, to label the newly
      generating cells. Rats were killed 15 days after TBI, and coronal brain sections
      were stained immunohistochemically with diaminobenzidine to identify newly
      generating bromodeoxyuridine-positive cells. To study the differentiation of
      newly generating cells into neurons, sections were also double-stained for
      neuronal markers (Tuj1, doublecortin, NeuN) with fluorescein isothiocyanate.
      RESULTS: The data demonstrate that newly generating cells were mainly present in
      the subventricular zone, hippocampal formation, and boundary zone of contusion of
      both treated and control animals. Intracerebral MSC treatment significantly
      increased the progenitor cell proliferation in the subventricular zone and
      boundary zone compared with the controls, whereas intravenous MSC treatment
      enhanced this endogenous proliferation in subventricular zone, hippocampus, and
      boundary zone. In both groups, some of the new cells revealed positive staining
      for neuronal markers. A statistically significant functional improvement was
      observed in both the intracerebrally as well as intravenously treated groups.
      CONCLUSION: Intracerebral and intravenous MSC administration promotes endogenous
      cellular proliferation after TBI in rats. This may contribute to the functional
      improvement observed in these rats.

PMID- 15509326
TI  - Systematic comparison of dendritic cell-based immunotherapeutic strategies for
      malignant gliomas: in vitro induction of cytolytic and natural killer-like T
      cells.
AB  - OBJECTIVE: To compare the efficacy of various immunotherapeutic strategies of
      loading dendritic cells (DCs) with whole-glioma cell antigens and characterize
      the effector responses induced. METHODS: DCs were either fused with major
      histocompatibility complex (MHC)-matched glioma cells (Fusion) or pulsed with
      apoptotic tumor cells (DC/Apo), total tumor ribonucleic acid (RNA) (DC/RNA), or
      tumor lysate (DC/Lys). These tumor-DC preparations were then assessed for their
      phenotype, cytokine profile, and capacity to stimulate autologous peripheral
      blood mononuclear cells (PBMCs) in vitro. Phenotype and tumor-specific cytolytic
      activities of various effector cell populations were characterized and compared.
      RESULTS: The various tumor-DC preparations exhibited similar phenotype and
      cytokine profiles irrespective of the method of loading tumor-cell antigens.
      However, the fusion, DC/Apo, and DC/RNA induced superior tumor cytolytic
      activities in PBMCs compared with DC/Lys or DC and tumor controls. DC/Apo induced
      the greatest expansion of tumor-specific lymphocytes, as detected by trypan blue
      exclusion and thymidine incorporation assays. Flow cytometric analyses also
      revealed the highest relative percentages of T helper cells (CD3+CD4+), cytotoxic
      T lymphocytes (CTLs) (CD3+CD8+), and natural killer (NK)-like T cells (CD3+CD56+)
      in the DC/Apo group among all the groups studied, indicating that DC/Apo induced
      expansion of PBMCs bearing multiple T and NK cell markers. Interestingly,
      isolated NK-like T cells demonstrated significantly higher tumor cytotoxicity
      compared with CTLs isolated from the same groups and was also non-MHC-restricted.
      CONCLUSION: Apoptotic tumor cells may be an optimal source of whole-tumor-cell
      antigen for immunotherapy of gliomas. The study also demonstrates for the first
      time that both CTLs and NK-like T cells are expanded and stimulated by mature,
      tumor-pulsed DCs.

PMID- 15509327
TI  - Mustafa Sakarya (1901-1988): Turkish fellow of Walter E. Dandy.
AB  - Walter E. Dandy is one of the true pioneers of modern neurosurgery. This eminence
      led many surgeons to visit his department for training. Mustafa Sakarya, a
      Turkish surgeon, was Dr. Dandy's only fellow from Turkey. He spent 9 months at
      the Johns Hopkins Hospital and wrote his observations in a notebook during this
      period. The notebook contains information regarding the patients, operative
      schedules, and surgical techniques, as well as theoretical reviews. His notes are
      of potential interest to both American and Turkish neurosurgeons.

PMID- 15509328
TI  - Stereotactic surgery: the early years.
AB  - ALTHOUGH STEREOTACTIC SURGERY was conceived at the turn of the 20th century,
      human applications did not gain momentum until the 1950s. Modern stereotactic
      surgery, as currently practiced, has rapidly developed in the past decade with
      computer assistance obviating the need for invasive localization techniques and
      ultimately leading to the development of frameless instruments. Applications of
      these techniques have also greatly expanded the use of stereotactic methods
      beyond functional neurosurgery. This article describes the author's involvement
      in the early development of stereotactic surgery, beginning in the late 1950s.
      With the recognition that physiological confirmation of targets is important in
      improving the safety and accuracy of functional stereotactic surgery, a number of
      approaches were developed that are still in use today.

PMID- 15509329
TI  - The science of shrinking human heads: tribal warfare and revenge among the South
      American Jivaro-Shuar.
AB  - THE PRACTICE OF "head-shrinking" has been the proper domain not of Africa but
      rather of the denizens of South America. Specifically, in the post-Columbian
      period, it has been most famously the practice of a tribe of indigenous people
      commonly called the Jivaro or Jivaro-Shuar. The evidence suggests that the Jivaro
      Shuar are merely the last group to retain a custom widespread in northwestern
      South America. In both ceramic and textile art of the pre-Columbian residents of
      Peru, the motif of trophy heads smaller than normal life-size heads commonly
      recurs; the motif is seen even in surviving carvings in stone and shell.
      Moreover, although not true shrunken heads, trophy heads found in late pre
      Columbian and even post-Columbian graves of the region demonstrate techniques of
      display very similar to those used by the Jivaro-Shuar, at least some of which
      are best understood in the context of head-shrinking. Regardless, the Jivaro
      Shuar and their practices provide an illustrative counterexample to popular myth
      regarding the culture and science of the shrinking of human heads.

PMID- 15509331
TI  - Intersubjectivity in psychoanalysis.

PMID- 15509332
TI  - Narcissistic configurations: violence and its absence in treatment.
AB  - 'On narcissism: An introduction' constitutes a turning point in psychoanalysis.
      Although narcissism is a concept which has not been explicitly referred to by
      many important thinkers for decades, it could be said that there is no paper
      written in psychoanalysis since Freud that does not implicitly take into account
      the modifications in thinking that the work brought about. In this paper, the
      author contrasts two types of narcissistic configurations: in the first, the
      intolerance of the other is dealt with by expulsion and violence; in the second,
      by withdrawal. The author contrasts patients who express manifest violent
      behaviour with patients for whom the violent behaviour is absent but who,
      nevertheless, present similar background histories, which might have led to a
      prediction of violence. They are also profoundly different in terms of what they
      provoke in the countertransference. In addition, this paper argues that the
      treatment of narcissistic personalities has allowed in recent years the
      understanding of a modality of depression. Following Green, the author argues
      that, instead of a fruitless debate that involves evolutionary issues around the
      concept of narcissism, it is necessary to distinguish the narcissistic aspect in
      any analytic relationship, to identify the narcissistic transference in different
      types of psychopathologies.

PMID- 15509333
TI  - The seventh servant: the implications of a truth drive in Bion's theory of 'O'.
AB  - Drawing upon Bion's published works on the subjects of truth, dreaming, alpha
      function and transformations in 'O', the author independently postulates that
      there exists a 'truth instinctual drive' that subserves a truth principle, the
      latter of which is associated with the reality principle. Further, he suggests,
      following Bion's postulation, that 'alpha-function' and dreaming/phantasying
      constitute unconscious thinking processes and that they mediate the activity of
      this 'truth drive' (quest, pulsion), which the author hypothesizes constitutes
      another aspect of a larger entity that also includes the epistemophilic component
      drive. It purportedly seeks and transmits as well as includes what Bion (1965,
      pp. 147-9) calls 'O', the 'Absolute Truth, Ultimate Reality, O' (also associated
      with infinity, noumena or things-in-themselves, and 'godhead') (1970, p. 26). It
      is further hypothesized that the truth drive functions in collaboration with an
      'unconscious consciousness' that is associated with the faculty of 'attention',
      which is also known as 'intuition'. It is responsive to internal psychical
      reality and constitutes Bion's 'seventh servant'. O, the ultimate landscape of
      psychoanalysis, has many dimensions, but the one that seems to interest Bion is
      that of the emotional experience of the analysand's and the analyst's 'evolving
      O' respectively (1970, p. 52) during the analytic session. The author thus
      hypothesizes that a sense of truth presents itself to the subject as a quest for
      truth which has the quality and force of an instinctual drive and constitutes the
      counterpart to the epistemophilic drive. This 'truth quest' or 'drive' is
      hypothesized to be the source of the generation of the emotional truth of one's
      ongoing experiences, both conscious and unconscious. It is proposed that emotions
      are beacons of truth in regard to the acceptance of reality. The concepts of an
      emotional truth drive and a truth principle would help us understand why
      analysands are able to accept analysts' interpretations that favor the operation
      of the reality principle over the pleasure principle--because of what is
      postulated as their overriding adaptive need for truth. Ultimately, it would seem
      that Bion's legacy of truth aims at integrating finite man with infinite man.

PMID- 15509334
TI  - Transformations of early infantile experiences: a 6-month-old in psychoanalysis.
AB  - The aim of the paper is to study the theoretical and technical tools for
      psychoanalysis adapted to an infantile analysand's requirements. The author
      presents the case of a 6-month-old boy with his mother in psychoanalytical
      sessions four times a week; the analysis was terminated after six weeks. After
      the first two sessions the disturbances between the infant and the mother
      disappeared from everyday life but continued with increasing intensity as an
      emotional storm in the sessions during three weeks up to a 12-day break. During
      and after the break everyday life continued without disturbances. After the break
      the emotional storm continued in the sessions but abated and was replaced by
      playing. The infant's creation of a 'fort-da' game with his pacifier indicated a
      transformation of the mental functioning. The analysis could then be terminated.
      The study of the process indicates good reasons to adapt psychoanalytical
      concepts to the prerequisite of the infantile personality and to use the concepts
      of 'unconscious', 'infantile repression', 'substitute formation', 'return of the
      infantile repressed', 'infantile transference', 'splitting', 'xKy', 'reverie' and
      'containment' as some of the theoretical tools for understanding the infantile
      personality in a clinical psychoanalytical setting.

PMID- 15509335
TI  - Reflections on Bion's 'elements of psychoanalysis': experience, thought and
      growth.
AB  - This paper aims to follow, in Bion's conception of analytic work, an axis of
      reflection organized around three preoccupations: favoring emergence of emotional
      experience, symbolic elaboration of that experience and resuming growth through
      symbolic thought. The overarching issue and condition of all three is the
      capacity to contain the largest possible range of transferential and
      countertransferential facts in analytic sessions. This range is likely to be
      reduced if the analyst listens to the experience of a session with too great a
      number of theoretical elements in mind. Hence the dictum 'To listen without
      memory and desire', which will be commented upon here in parallel with the
      process of abstraction, a process serving in Bion's writings the purpose of
      dealing both with the epistemological problem of communication among analysts and
      with the clinical problem of receptiveness to the unknown.

PMID- 15509336
TI  - At-one-ment, intuition and 'suchness'.
AB  - Many senses exist for perceiving sensory experience; there are in turn others
      which make it possible to perceive emotional experience: intuition is one of
      these. The author, using W. R. Bion's work, studies intuition psychoanalytically,
      considering it to be a powerful 'sense' in clinical work. He describes the
      metapsychology of intuition, and proposes models that make it possible to think-
      from different perspectives--about how to make use of it in an analysis. To this
      end, he examines a series of useful processes and concepts: growth, tolerance,
      'suchness', suffering and courage. The author defi nes the intuitive mechanism as
      a derivation of the renunciation of memory, desire and understanding; such a
      renunciation, learning from the experience of suffering the pain of facing the
      Truth in at-one-ment, makes it possible to tolerate the frustrations associated
      with observing the analysand 'such-as-he-is'. Finally, once immersed in the
      intelligence of intuition, the author considers ways in which intuition might be
      linked with concepts, with a view to interpreting the facts that must be
      transformed in the analysis.

PMID- 15509337
TI  - Another language, another place: to hide or be found?
AB  - The author examines some specific features of the analytic encounter when both
      patient and analyst are emigres from the same cultural and linguistic background.
      This can result in splitting processes that operate silently and are difficult to
      reach, but can also provide rich material, as they offer the couple the
      opportunity to work through the pain and the guilt over what is lost--ultimately
      the lost mother--murdered and betrayed. Working through the split faces the
      analyst with important technical considerations, bearing in mind that the shared
      cultural identity can conceal itself in the more undifferentiated features of the
      couple's psyche and be projected on to the setting. As such, it needs to be put
      to analytic scrutiny if the treatment is to avoid a stalemate. These are specific
      cultural defences deployed in the problematic existential encounter with the
      foreigner/other within oneself. Using clinical material from two cases, the
      author shows how the couple's access to a dual linguistic signifying system can
      enrich the analytic dialogue, but can also result in enactment. Careful
      monitoring of the transference-countertransference relationship is essential to
      the progress of the analytic work.

PMID- 15509338
TI  - 'This is not psychoanalysis': on the stony way of the Danish Psychoanalytical
      Society.
AB  - When Freud founded the International Psychoanalytical Association (IPA), he
      wanted a network of local groups responsible for psychoanalytic training. The
      groups would function as 'headquarters whose business it would be to declare:
      "All this nonsense is nothing to do with analysis; this is not psychoanalysis".'
      Today, with psychoanalytic pluralism, Tuckett (in press) has asked 'Does anything
      go?' He has pointed out that the psychoanalytic community has been increasingly
      willing to accept within its ranks apparently very varied approaches to theory
      and practice, and that this increasing diversity has many negative consequences
      for psychoanalytic institutions and especially for training schemas. The aim of
      this paper is to give an example of psychoanalysis that 'did not go', and how
      that led to a shaky start for the new Danish Psychoanalytical Society, with
      confusing boundary relations between psychoanalysis and psychotherapy and no
      training institute. Beginning with the written psychoanalytical contribution of
      the three founders of the Danish Society, the paper will try to identify factors
      that contributed to the 'shaky start'. The paper will also examine how stones
      were removed from the path, thus paving the way for the members of the Society to
      discover 'competent psychoanalysis'.

PMID- 15509340
TI  - Truth.

PMID- 15509339
TI  - The psychopathology of everyday Vienna: psychoanalysis and Freud's familiars.
AB  - This paper examines the parapraxes made by, to or about Jewish-identified
      individuals discussed by Freud in Psychopathology of everyday life. Each of these
      errors and slips is occasioned by what he terms a 'mesalliance' between a Jew and
      a Gentile. Such incidents of distorted language betray unresolved ambivalences
      and unformulated anxieties endemic to Jewish-Gentile interaction in Freud's
      Vienna. First, the disturbed relationships between German-speaking Gentiles and
      their threatening Doppelganger, the Jews, are analyzed by means of Freud's
      analysis of the 'uncanny' and an examination of the particular restrictions
      placed upon the 'officially' emancipated Jews in the Habsburg Empire, especially
      with regard to intermarriage. Then, the paper turns to Freud's discussions of
      explicitly Jewish-identified individuals and their limitation to illustrating
      parapraxes associated with what should be the most pleasurable and intimate
      relationships between Jew and Gentile, namely sexual and connubial relations. His
      focus upon this conflicted conjunction diagnosed the intrinsically problematic
      character of Jew-Gentile interaction in his Vienna.

PMID- 15509341
TI  - Psychoanalytic treatments of schizophrenic patients.

PMID- 15509342
TI  - The breast in female sexuality.

PMID- 15509343
TI  - The frontiers of psychopathology: new cultures, new patients?

PMID- 15509344
TI  - Beyond the limits: historical perspectives on boundary violations in
      psychoanalytic treatment.

PMID- 15509345
TI  - Working with psychotic and non-psychotic patients in situations of terror and
      military dictatorships.

PMID- 15509346
TI  - Freudian and Lacanian approaches to the clinical case: listening, interpretation,
      transference and countertransference.

PMID- 15509347
TI  - Contrasting clinical techniques: a British Kleinian, contemporary Freudian and
      Latin American Kleinian discuss clinical material.

PMID- 15509348
TI  - How is trauma transmitted?

PMID- 15509349
TI  - The Middle East crisis: psychoanalytic reflections.

PMID- 15509350
TI  - Multiple approaches to a single case: conclusions. Psychic change: what and how?

PMID- 15509351
TI  - On: writing about patients III.

PMID- 15509352
TI  - Telling it and passing it on, rendering and remembering: on turning suffering
      into history--conspiracy.

PMID- 15509353
TI  - Differences between out-patients with physical disease and those with medically
      unexplained symptoms with respect to patient satisfaction, emotional distress and
      illness perception.
AB  - OBJECTIVES: This study aimed to assess whether patients with medically
      unexplained symptoms (MUS) attending cardiology and neurology out-patient clinics
      were less satisfied with their consultation than patients whose presenting
      symptoms were explained by an organic diagnosis. The multidimensional nature of
      satisfaction and its relationships with emotional distress and illness perception
      were also assessed within the two groups. DESIGN AND SETTING: A prospective
      cohort study was carried out at a large inner city teaching hospital.
      PARTICIPANTS: New attenders at cardiology and neurology out-patient clinics
      participated in the study. MEASURES: The Satisfaction Questionnaire, the Hospital
      Anxiety and Depression Scale (HADS), the Health Anxiety Questionnaire (HAQ) and
      the Illness Perception Questionnaire (IPQ) were used in the study. RESULTS: There
      were no overall significant differences in satisfaction between organic and MUS
      patients. Factor analysis yielded four factors: satisfaction with information,
      satisfaction with style of doctor-patient interaction, satisfaction with clinic
      environment, and satisfaction with patient's health. Levels of internal
      consistency were good, with Cronbach's alphas between .74 and .95 for the four
      subscales. CONCLUSION: When considering patients with MUS, these findings
      emphasize the need to examine healthcare satisfaction from a detailed and
      multidimensional perspective. Relationships between satisfaction dimensions,
      clinic specialties and measures of psychological well-being and of illness
      perception show interesting patterns. These findings raise both theoretical and
      service delivery questions concerning communication strategies.

PMID- 15509354
TI  - Belief importance and the theory of planned behaviour: comparing modal and ranked
      modal beliefs in predicting attendance at breast screening.
AB  - OBJECTIVE: The objective of this study was, to compare the predictive utility of
      two measures of the attitude, subjective norm and perceived behavioural control
      constructs of the theory of planned behaviour (TPB; Ajzen, 1991) in predicting
      intention and subsequent attendance at breast screening. One construct was based
      on a modal set of underlying beliefs; the other was based on the three beliefs
      from each construct considered by the participant to be the most important.
      METHOD: We used a prospective, longitudinal design using a postal questionnaire
      at Time 1 and objective attendance data from screening records at Time 2.
      Questionnaires were sent to 1657 women from southeast England due to be invited
      for X-ray mammography under the UK's National Health Service Breast Screening
      Programme. After evaluating a set of modal behavioural, normative and control
      beliefs, women were asked to select the three beliefs they saw as the most
      important for them, and to rank them. The products of these three beliefs formed
      the 'important' (vs. the modal) measures. RESULTS: The 'important' attitude and
      subjective norm measures showed similar associations with direct measures and
      were equivalent to the modal measures in predicting intention and attendance at
      screening. The modal control construct was marginally more robust than the
      'important' one in its association with the direct measure of control, and with
      intention. Key individual important beliefs that predicted intention and
      behaviour were identified. CONCLUSIONS: Measuring belief importance can help more
      fully identify the structures underlying attitude, subjective norm and perceived
      behavioural control, and can provide useful information when the TPB is used as
      the basis for intervention to help change behaviour.

PMID- 15509355
TI  - Psychological distress in couples dealing with colorectal cancer: gender and role
      differences and intracouple correspondence.
AB  - OBJECTIVES: This longitudinal study examined patterns of psychological distress
      in couples facing colorectal cancer within 6 months after surgery. In addition,
      correspondence in psychological distress was investigated between patients and
      their spouses, taking into account the gender of the patient. METHOD: The study
      had a longitudinal design, involving three assessment points; (T1) within 2 weeks
      after surgery, (T2) 3 months after baseline and (T3) 6 months after baseline. At
      T1, respondents were asked to indicate how they felt during the week prior to
      surgery. At T2 and T3, respondents reported their feelings during the preceding
      week. Psychological distress was measured using the 20-item Center for
      Epidemiologic Studies Depression Scale (CES-D) in 137 couples. RESULTS:
      Concerning the week prior to surgery, females reported more distress being a
      patient, whereas males reported more distress being a spouse. In comparison with
      a reference group, females as well as males, regardless of their role, showed
      increased levels of psychological distress prior to surgery. At 3 and 6 months
      following surgery, increased levels of distress continued to exist in females,
      whereas males' distress returned to normal levels. Neither within female-patient
      couples, nor within male-patient couples, were associations between patients' and
      spouses' distress found. CONCLUSION: We demonstrated a considerable impact of the
      cancer diagnosis on both female and male patients and their spouses before and 3
      months after surgery. Six months after surgery, females, in particular, appear to
      be vulnerable to distress.

PMID- 15509356
TI  - Encouraging young males to perform testicular self-examination: a simple, but
      effective, implementation intentions intervention.
AB  - OBJECTIVES: The objective of this study was to examine the effectiveness of a
      simple psychological intervention known as 'implementation intentions' to promote
      performance of testicular self-examination (TSE) in a sample of young males.
      METHOD: A prospective, randomized controlled design measured knowledge of
      testicular cancer, prior experience with TSE and intention to perform TSE within
      a 3-week period. Participants in the intervention group were instructed to
      formulate specific plans for when and where they would perform TSE. Three weeks
      later, a second questionnaire assessed self-reported performance of TSE during
      the study period and future intention to perform TSE. One hundred and fifty-nine
      male undergraduates aged between 18 and 35 were assigned, at random, to an
      intervention or non-intervention group. Men over 35 were excluded so that the
      sample reflected the highest risk age group for testicular cancer. Just under
      half the original participants (76/159) completed the study. We measured
      performance of TSE and future intention to perform TSE. RESULTS: Responders and
      non-responders did not differ on any of the measures assessed at Time 1. At Time
      2, 30 (65%) participants in the intervention reported performing TSE compared
      with 12 (40%) in the control condition, and chi-squared analyses revealed that
      the difference was significant. CONCLUSIONS: The implementation intentions
      intervention procedure, which encourages the use of environmental and contextual
      'cues' to prompt a desired behaviour, appears to offer a promising strategy for
      encouraging the performance of TSE.

PMID- 15509357
TI  - The role of perceived need within the theory of planned behaviour: a comparison
      of exercise and healthy eating.
AB  - OBJECTIVES: This study examined the effect of perceived need on exercise and
      healthy eating using the theory of planned behaviour (TPB). In addition, it
      investigated the determinants of perceived need. METHOD: Participants completed a
      questionnaire measuring components of TPB and perceived need. A follow-up
      questionnaire 1 week later measured behaviour. The questionnaires were completed
      by e-mail. The initial questionnaire was completed by 331 adults, and 286 follow
      up questionnaires were returned. RESULTS: Perceived behavioural control was the
      main predictor of exercise intention and affective attitude was the main
      predictor of healthy eating intention. Perceived need significantly contributed
      to the prediction of healthy eating intention but not to exercise intention.
      Intention and perceived behavioural control predicted actual behaviour but
      perceived need did not. Reasons reported for the perception of needing to engage
      in both behaviours mainly focused on physical health and weight control.
      CONCLUSIONS: Reasons reported for low perceived need suggest that the concept of
      perceived need may be rather ambiguous, particularly in the case of exercise.
      Therefore, further research is needed to elucidate the role of perceived need in
      relation to a variety of health behaviours.

PMID- 15509358
TI  - Promoting exercise behaviour: an integration of persuasion theories and the
      theory of planned behaviour.
AB  - OBJECTIVES: The purpose of this study was to examine the effectiveness of a
      theoretical integrated persuasive message on exercise motivation in college
      students. METHOD: Four hundred and fifty introductory psychology students (M age
      = 20.02 years; SD = 3.94) were randomly assigned to reading positively or
      negatively framed strong messages advocating exercise. The messages were
      attributed to a credible source, a non-credible source or to a no-source control
      condition. Theory of planned behaviour (TPB) constructs (i.e. attitude,
      subjective norm, perceived behavioural control) and cognitive responses (i.e.
      thought listing) were measured immediately and 2 weeks following the delivery of
      the intervention. RESULTS: Unfortunately, the results did not corroborate
      previous research, as we did not find any significant effects between
      experimental groups on any psychological or behavioural variable. CONCLUSIONS:
      There may be several potential explanations for the lack of effects, including
      the interaction between the type of persuasive information (TPB implications) and
      sources of persuasion and how these persuasive messages are processed
      (elaboration likelihood model/cognitive response implications). The theoretical
      implications of this research are discussed with a view towards future directions
      for exercise promotion initiatives using theoretically driven interventions.

PMID- 15509359
TI  - Subjective health and fibrinogen in a healthy Chinese cohort.
AB  - OBJECTIVES: This study explores standard cardiovascular (CVD) risk factors in a
      healthy population sample, with low CVD prevalence and presumed higher social
      connectedness as potential mechanisms linking subjective health (SH) and physical
      health. METHOD: A population-based, telephone-sampled, cross-sectional study
      recruited a healthy subset of 2280 Chinese adults who subsequently underwent a
      free medical examination. Serum total cholesterol, low-density lipoproteins
      (LDL), high-density lipoproteins (HDL), triglycerides, fibrinogen, fasting
      glucose, 2-hour post-load glucose, blood pressure and adiposity were compared
      between respondents reporting good SH and those reporting poor SH over the past 3
      months, on a 4-point, single-item measure. RESULTS: After adjustment for age,
      gender, education, exercise, marital and smoking status, only serum fibrinogen
      significantly differentiated the two groups. Respondents reporting Very poor or
      Poor SH had a significantly greater likelihood of raised mean fibrinogen levels
      compared with those reporting Good or Very good SH (Adjusted Odds Ratio 1.37, 95%
      CL 1.002-1.84, p < .05). CONCLUSIONS: There is a small but robust association
      between SH and fibrinogen in this low CVD prevalent population unexplained by
      known pre-existing disease.

PMID- 15509360
TI  - Appraisal theory and emotional sequelae of first visit to colposcopy following an
      abnormal cervical screening result.
AB  - OBJECTIVES: Attendance at colposcopy following an abnormal cervical smear is
      potentially a highly distressing event. This study evaluates the role of
      cognitive appraisal components (Lazarus, 1991; Smith et al., 1993) in explaining
      emotional reactions to this event. We also compare the psychological sequelae of
      immediate treatment at first colposcopy (See and Treat, ST) vs. colposcopy with
      treatment deferred to a later date (Diagnose and Defer, DD). METHOD: One thousand
      and eighty-five women referred for colposcopy completed a questionnaire assessing
      appraisal and emotion following their attendance. Clinical data were abstracted
      from medical records and social deprivation scores were estimated from postal
      code information based on normative data. RESULTS: Diagnosis and cognitive
      appraisals were each significantly associated with emotion, together accounting
      for between 3 and 15% of variance in different emotions. Specific patterns of
      appraisal explained specific emotions in line with theoretical predictions. Women
      with Cervical Intraepithelial Neoplasia (CIN) 2 or CIN 3 undergoing 'ST' were
      less anxious, less embarrassed and significantly more relieved compared with a
      matched sample of women undergoing 'DT', and perceived their first appointment as
      more motivationally congruent. CONCLUSION: Diagnosis, motivationally incongruent
      experiences and low emotion-focused coping potential are the most important
      determinants of anxiety after colposcopy. 'See and Treat' appears to have a
      positive psychological impact by increasing motivational congruence.

PMID- 15509361
TI  - Does perceived behavioural control mediate the relationship between power beliefs
      and intention?
AB  - OBJECTIVES: In order to determine whether the relationship between power beliefs
      (Sigma(p)) and health-related behavioural intentions is mediated by perceived
      behavioural control (PBC) we used structural equation modelling of eight cross
      sectional data sets. METHOD: Eight studies that examined health-related
      behaviours and employed representative samples totalling N = 4663 participants
      were analysed. All studies involved power belief items derived from pilot testing
      and employed standard multi-item measures of power beliefs, PBC and intention
      that were highly reliable. RESULTS: Confirmatory factor analysis confirmed the
      discriminant validity of power beliefs, PBC and intention. Structural equation
      modelling of relevant paths indicated that PBC only partially mediated the
      relationship between power beliefs and intention (Z(Sobel) = 5.15, p < .001;
      Z(Baron&Kenny) = 5.16, p < .001). Power beliefs had a significant direct
      relationship with intention even after PBC had been taken into account.
      CONCLUSION: The findings undermine Ajzen's contention that PBC mediates the power
      beliefs-intention relationship and suggests that it is important to employ
      measures of power beliefs in addition to measures of PBC in order to enhance the
      prediction of intentions to perform health-risking, or health-promoting,
      behaviours.

PMID- 15509362
TI  - Social support, anxiety and depression after chemotherapy for ovarian cancer: a
      prospective study.
AB  - OBJECTIVES: We aimed to describe the levels of anxiety and depression in patients
      during the 3 month period following the end of chemotherapy treatment and to
      identify factors that predict psychological morbidity. METHOD: We performed a
      prospective study in women with ovarian cancer to determine the changes in
      psychological status in the 3 months following completion of chemotherapy. Sixty
      three consecutive patients were assessed at the completion of chemotherapy (Time
      1) and 57 at 3 months follow-up (Time 2). Relevant disease and patient
      characteristics were recorded and patients were assessed at Time 1 for anxiety,
      depression and their perception of emotional support, an index of their
      psychosocial environment. Anxiety and depression were re-assessed at Time 2.
      RESULTS: The results indicate significant initial psychological morbidity, with
      clinical caseness for anxiety (38%) and depression (33%) being common. Follow-up
      at Time 2 shows that patients undergo a significant reduction in cases (19%) and
      symptoms of depression but an increase in cases of anxiety (47%). The principal
      factors associated with symptoms of anxiety at Time 2 were poor perceived social
      support, increased intrusive thoughts and, to a lesser extent, younger age.
      Medical parameters, such as the stage of disease, response of the cancer to
      treatment, Ca125 (a tumour glycoprotein) and Karnofsky Performance status (a
      measure of how well the patients is) were not associated with worse psychological
      outcome. CONCLUSION: These data show for the first time that social support and
      intrusive thoughts, rather than physical parameters, are the principal
      determinants of psychological morbidity in patients with ovarian cancer.

PMID- 15509363
TI  - Supracricoid partial laryngectomy with cricohyoidopexy and
      cricohyoidoepiglottopexy: functional and oncological results.
AB  - Sixty-eight patients who presented with glottic and glottosupraglottic squamous
      cell carcinoma and who were managed in this department with supracricoid partial
      laryngectomy (SCPL) with either cricohyoidoepiglottopexy (CHEP) or
      cricohyoidopexy (CHP), were retrospectively reviewed. The authors analysed the
      functional and oncological results of the patients. The median follow-up period
      was 62 months. The average times until decannulation and nasogastric feeding tube
      removal were 27.7 and 26.4 days, respectively. All patients were successfully
      decannulated. All patients were able to swallow, but one patient was unable to
      swallow and had recurrent aspiration. Better functional results were achieved in
      patients managed with CHEP procedure than the patients managed with CHP
      procedure. The five-year absolute and cause-specific actuarial survival rates
      (Kaplan-Meier method) were 78.6 per cent and 93.9 per cent, respectively. The
      five-year actuarial local control and nodal control rates were 89.5 per cent and
      90.4 per cent, respectively. Local recurrence was statistically more likely in
      patients with positive resection margins (p <0.006). Overall, local control and
      laryngeal preservation were achieved in 95.6 per cent and 89.7 per cent,
      respectively. Supracricoid partial laryngectomy procedures (CHEP and CHP) are
      possible alternatives to total laryngectomy in the treatment of selected advanced
      glottic and glottosupraglottic carcinomas.

PMID- 15509364
TI  - Studies of the cell cycle regulatory proteins P16, cyclin D1 and retinoblastoma
      protein in laryngeal carcinoma tissue.
AB  - Defects in the system controlling the cell cycle can lead to an increased
      proliferation of cancer cells. The aim of this study was to analyse the
      immunohistochemical expression of chosen cell cycle proteins (P16, cyclin D1 and
      retinoblastoma protein) and their connection with the clinical course of the
      disease in laryngeal squamous cell cancer (LSCC). Cancer tissue sections obtained
      from 58 patients after total laryngectomy served to determine the level of the
      proteins' expression using immunohistochemical staining and commercial
      antibodies. A decreased level of P16 expression in 47 per cent, of retinoblastoma
      protein in 12 per cent and strong cyclin D1 expression in 48 per cent of cases
      was revealed. Our results show significant correlation between decreased P16
      expression and increased tumour dedifferentiation. Overexpression of cyclin D1
      was statistically more common in locally advanced tumours (T(3) -T(4)). Low
      expression of retinoblastoma protein was significantly correlated with both
      positive P16 immunostaining and with strong cyclin D1 expression. Our study
      confirms that dysfunction of cell cycle regulation is a common event and may play
      a significant role in the development of squamous cell carcinoma of the larynx.

PMID- 15509365
TI  - Meniere's disease and allergy: allergens and cytokines.
AB  - The aim of this article is to evaluate the role of allergy in the pathogenesis of
      Meniere's disease by means of cytokine profiles, allergic parameters and
      lymphocyte subgroups. A total of 46 patients aged between 26-68 years diagnosed
      with Meniere's disease between 1993-2002 were recruited to this study. The
      control group consisted of 46 healthy volunteers who were from the same age
      group, living in the same region and possessing similar socioeconomic indicators.
      Lymphocyte subgroups were measured from the peripheral blood by employing Becton
      Dickinson (BD) monoclonal CD4, CD8, CD23 antibodies. IFN-gamma, IL4, total IgE
      levels, and specific IgE levels pertaining to tree, fungus, fruit, egg-white,
      cow's milk, wheat flour, corn flour, beef, and rice allergens, in all seasons,
      were measured and compared in the patient and control groups. In patient serum
      samples there were positive correlations between CD23 and IgE, CD8 and IgE,
      CD4/CD8 and IgE, and CD23 and CD8 (p <0.01). There were negative correlations
      between IL-4 and IFN-gamma, IFN-gamma and IgE, and a positive correlation between
      IL-4 and IgE. Total IgE levels were above the normal values in 19/46 (41.3 per
      cent) of the patient group, but the ratio was nine out of 46 (19.5 per cent) in
      the control group. A history of allergy was found in 31/46 (67.3 per cent) when
      the patients were questioned. The ratio of a history of allergy was 16/46 (34.7
      per cent) in the control group. When specific IgE levels were evaluated the ratio
      of patients with all the panels negative was eight out of 46 (17.9 per cent), but
      it was 31/46 (67.3 per cent) in the control group. This study found that the
      prevalence of allergy was higher in patients with Meniere's disease than in the
      control group. Thus the authors suggest that allergy should be taken into account
      when patients with this disease are treated.

PMID- 15509366
TI  - Cost and morbidity of MRSA in head and neck cancer patients: what are the
      consequences?
AB  - Methicillin resistant Staphylococcus aureus (MRSA) has become a prevalent
      nosocomial pathogen worldwide. The objectives of this study were to assess the
      morbidity and cost associated with the treatment of head and neck cancer patients
      who become colonized or infected with MRSA following major surgical procedures.
      We present a retrospective review of patients who underwent major surgery for
      head and neck cancer over a one year period and who then became MRSA positive in
      the post-operative period. MRSA affected 25/55 (45 per cent) patients who
      underwent major head and neck procedures during the period studied. The mean time
      of diagnosis was 13 days post-surgery. Morbidity included cellulitis,
      osteomyelitis and MRSA pneumonia. Thirteen of the patients who became MRSA
      positive (52 per cent of the MRSA group) required further surgery including plate
      removal, new flap formation and wound debridement as a result of the infection.
      Average in-hospital stay was almost three times more prolonged for patients who
      became MRSA positive compared to those who did not have MRSA. The costs of the
      first hospital stay were over three times more in the MRSA-positive group of
      patients. Antibiotic costs were increased by pound 2470 per patient because of
      MRSA. The extra stay in hospital, together with extra days in intensive care,
      extra medical and nursing care and additional costly antibiotic treatment, led to
      major cost implications and loss of health service resources in the unit. MRSA
      infection is a serious cause of morbidity in any surgical group of patients and
      this study focuses on the consequences for treatment of head and neck cancer
      patients in particular.

PMID- 15509367
TI  - The place of Riedel's procedure in contemporary sinus surgery.
AB  - Many operative procedures have been described to treat frontal sinus disease with
      varying results. Obliteration of the frontal sinus is attempted when drainage
      procedures fail. Most large series of patients undergoing sinus obliteration have
      reported recurrent disease yet the management of these patients is rarely
      discussed. We believe Riedel's procedure has an important role in the management
      of these patients. Riedel's procedure can help eradicate frontal sinus disease
      and symptoms when drainage and obliteration have failed and where there is
      persistent disease involving the anterior wall of the frontal sinus or the sinus
      itself. Whilst cranialization has a role in the removal of the mucosa or contents
      of the frontal sinus in craniofacial resection, the morbidity associated with it
      make Riedel's procedure preferable for dealing with chronic infection or locally
      invasive disease. Riedel's procedure also maintains a barrier in the form of the
      posterior wall of the frontal sinus and the intracranial contents. Post-operative
      disfigurement, the main criticism of this procedure, can be reduced to some
      extent by chamfering the margins of the frontal sinus along with the supraorbital
      rims and reconstructing the anterior wall at a later date if necessary. The
      authors are aware that any report about frontal sinus surgery should be judged
      after several years follow-up, and whilst not all these cases have been
      asymptomatic for a decade, several have been reviewed for many years.

PMID- 15509368
TI  - Clinical evaluation of the electronic nose in the diagnosis of ear, nose and
      throat infection: a preliminary study.
AB  - The term electronic nose describes an electronic system that is able to mimic the
      human sense of smell. Electronic noses have been developed over the last 10 or
      more years to perform a variety of identification tasks in various industries.
      More recently electronic noses have attracted new interest in their application
      in the field of medical diagnosis. The aim of this study is to explore the use of
      an electronic nose to identify and classify pathogens associated with ear, nose
      and throat (ENT) infections. In this study 90 bacterial swab samples were
      collected from 90 patients with ENT infections. Some of these samples were
      analysed immediately with a commercial electronic nose (Cyranose C320). Similar
      numbers of swabs were also taken from the same site of infection and were sent
      for microbiology culture and sensitivity. The electronic nose diagnosis was
      compared with the microbiology diagnosis and it was found that the electronic
      nose diagnosis was correct in 88.2 per cent of the cases, which is an encouraging
      result.

PMID- 15509369
TI  - Bacterial colonization of laryngectomy stomas.
AB  - Infections with organisms resistant to conventional antibiotics are of increasing
      concern. This observational study investigates the bacterial colonization of the
      peristomal area of laryngectomy patients. Thirty-two consecutive patients who had
      previously undergone laryngectomy were recruited from the Head and Neck Clinic of
      a teaching hospital. Swabs were taken from the laryngectomy stoma site, the mouth
      and both nasal cavities. Microbiological culture and isolation were performed
      following standard procedures. Despite no clinical sign of infection, 27 patients
      were found to be carriers of one or more organism (84.4 per cent). Staphylococcus
      aureus was detected in the peristomal area of 15 patients (46.9 per cent).
      Methicillin-resistant Staphylococcus aureus (MRSA) was isolated in seven (21.9
      per cent) cases. In this series the authors found a high incidence of
      colonization with potentially pathogenic bacteria in laryngectomy stomas with no
      clinical signs of infection. In a significant number of patients, Gram positive
      organisms were identified that could potentially cause cellulitis or wound
      infections.

PMID- 15509370
TI  - Posterior nasal cautery with silver nitrate.
AB  - A method of cauterizing the posterior parts of the nose without damage to the
      anterior mucosa is presented. A silver nitrate stick was sheathed within a cut
      segment of a nasogastric (NG) tube and endoscopically advanced within the nose
      until the vessel was reached. The stick was then pushed until the silver nitrate
      protruded and the vessel was cauterized.

PMID- 15509371
TI  - New method for raising the mucoperichondrial flap in septal surgery: microscope
      assisted hydrodissection technique.
AB  - An essential step in septal surgery is the correct identification of the
      subperichondrial plane. Access to this plane can be improved by hydrodissection
      under enhanced vision. Hydrodissection consists of pressure insufflation of fluid
      into an anatomical space with a consequent increase in the hydrostatic pressure
      that separates the tissue planes. In septal surgery, the subperichondrial plane
      is hydrodissected by infiltration of 2 ml of xylocaine with adrenaline. This
      creates a bloodless and wide surgical field that facilitates surgery. With the
      use of a surgical microscope equipped with a teaching arm, it is possible to
      teach nasal anatomy and septal surgery to trainees.

PMID- 15509372
TI  - Spontaneous cerebrospinal fluid otorrhoea via oval window: an obscure cause of
      recurrent meningitis.
AB  - Spontaneous cerebrospinal fluid (CSF) leak via the oval window is uncommon and
      can result in recurrent bacterial meningitis. Current understanding of
      spontaneous CSF otorrhoea is reviewed and a diagnostic algorithm is presented. A
      seven-year-old boy presented with bilateral congenital deafness and recurrent
      meningitis. High-resolution computed tomography (HRCT) of the temporal bone
      showed a labyrinthine deformity and communication between the internal auditory
      canal (IAC) and the cochlea. Subtotal petrosectomy with closure of the external
      acoustic meatus and eustachian tube was performed. Post-operatively, the child
      had no further episodes of meningitis. This rare and obscure cause of recurrent
      childhood meningitis requires a high index of suspicion and the use of diagnostic
      tools, especially HRCT.

PMID- 15509373
TI  - Facial baroparesis secondary to middle-ear over-pressure: a rare complication of
      scuba diving.
AB  - A facial nerve palsy, as a result of middle-ear high pressure, is a rare
      complication of sub-aqua diving. It may occur as a result of an acute pressure
      change in the middle ear during ascent in those patients who have experienced
      difficulty equalizing their middle-ear pressure during the prior descent. We
      present the case history of this occurring in a 21-year-old diver and discuss the
      pathophysiology, management and the previous literature. The correct diagnosis of
      this condition is important if unnecessary, and potentially hazardous,
      recompression treatment is to be avoided.

PMID- 15509374
TI  - Metastasizing mixed tumour of the parotid gland presenting as multiple lung
      metastases.
AB  - Metastasis is a feature of malignant neoplasms. Although rare, metastasizing
      pathologically benign mixed tumour has been reported. This report describes a 33
      year-old woman with multiple lung metastases from mixed tumour. A small
      preauricular mass had been removed 23 years earlier. Six years later, the patient
      had the same symptom; the recurrent mass was resected. She was not aware of the
      exact pathological diagnosis of the previous tumours. One of the most common
      features of metastasizing mixed tumour is recurrence at the primary site.
      Inadequate resection of the primary tumour is often associated with metastasis.
      Thus, it is important for the head and neck surgeon to be aware of the concept of
      pathologically benign metastasizing mixed tumour and the importance of adequate
      surgical procedure.

PMID- 15509375
TI  - Acute presentation of a fibroepithelial pharyngeal polyp.
AB  - We report the case of a 60-year-old Caucasian man who presented with choking and
      airway compromise due to a large pharyngeal polyp. It was resected as an
      emergency procedure and subjected to macroscopic and microscopic examination. The
      fibroepithelial polyp arose from the right pharyngeal wall and consisted of
      adipose tissue covered by squamous epithelium without evidence of malignancy.
      This is a particularly rare lesion in adults and there are few references in the
      medical literature. To our knowledge this is the first English case report of an
      acute presentation of adult fibroepithelial pharyngeal polyp. This case report
      also discusses the issues raised in the management of a potentially fatal lesion
      that may have resulted in complete airway obstruction.

PMID- 15509376
TI  - Pre-tracheal air cyst.
AB  - Pre-tracheal air cysts or aeroceles are rare complications of tracheostomy. This
      is believed to be the first reported case in an adult presenting with a pre
      tracheal air cyst 12 years after a tracheostomy. Only three case reports in
      children have been reported to date. The pathogenesis and treatment options are
      discussed and a method of managing this condition is suggested.

PMID- 15509377
TI  - Bow-shaped tracheal rings: the lesson learnt from an endotracheal intubation.
AB  - Tracheal abnormalities are extremely rare and can occur as a single congenital
      anomaly, as part of a wider spectrum of abnormalities [such as the syndrome of
      vertebral defects, anal atresia, tracheoesphageal fistula and/or oesophageal
      atresia, radial dysplasia, and renal defects (VATER), and the syndrome of
      vertebral defects, anal atresia, cardiovascular defects, tracheoesphageal fistula
      and/or oesophageal atresia, radial dysplasia, and renal and limb defects
      (VACTERL)] or in tracheomalacia. Congenital complete and near-complete tracheal
      rings are the more common morphological abnormalities that occur. A case of a
      long segment of bow-shaped, as opposed to horseshoe-shaped, tracheal rings is
      presented, along with a review of tracheal anatomy and embryology. This
      abnormality presented when, during repeated attempts at endotracheal intubation,
      the anaesthetist was consistently unable to ventilate the patient, whereas they
      were able to do so with a facemask. Bronchoscopy showed the posterior tracheal
      wall prolapsing into the airway, and radiology demonstrated this to be due to
      wide tracheal rings without any intrathoracic abnormality.

PMID- 15509378
TI  - Transient quadriplegia following re-puncture of tracheo-oesophageal fistula.
AB  - We present a case of a laryngectomized patient who underwent re-puncture of
      tracheo-oesophageal fistula for speaking valve voice restoration, resulting in a
      previously unreported inherent complication of this procedure: extradural abscess
      of the cervical spine with transient quadriplegia.

PMID- 15509379
TI  - Cost-effective analysis of conventional and nurse-led clinics for common
      otological procedures.

PMID- 15509380
TI  - Location, location, location.

PMID- 15509381
TI  - Mechanisms of eye gaze perception during infancy.
AB  - Previous work has shown that infants are sensitive to the direction of gaze of
      another's face, and that gaze direction can cue attention. The present study
      replicates and extends results on the ERP correlates of gaze processing in 4
      month-olds. In two experiments, we recorded ERPs while 4-month-olds viewed direct
      and averted gaze within the context of averted and inverted heads. Our results
      support the previous finding that cortical processing of faces in infants is
      enhanced when accompanied by direct gaze. However, this effect is only found when
      eyes are presented within the context of an upright face.

PMID- 15509382
TI  - Evidence of developmental differences in implicit sequence learning: an fMRI
      study of children and adults.
AB  - Prevailing theories of implicit or unaware learning propose a developmental
      invariance model, with implicit function maturing early in infancy or childhood
      despite prolonged improvements in explicit or intentional learning and memory
      systems across childhood. Neuroimaging studies of adult visuomotor sequence
      learning have associated fronto-striatal brain regions with implicit learning of
      spatial sequences. Given evidence of continued development in these brain regions
      during childhood, we compare implicit sequence learning in adults and 7- to 11
      year-old children to examine potential developmental differences in the
      recruitment of fronto-striatal circuitry during implicit learning. Participants
      performed a standard serial reaction time task. Stimuli alternately followed a
      fixed 10-step sequence of locations or were presented in a pseudorandom order of
      locations. Adults outperformed children, achieving a significantly larger
      sequence learning effect and showing learning more quickly than children. Age
      related differences in activity were observed in the premotor cortex, putamen,
      hippocampus, inferotemporal cortex, and parietal cortex. We observed differential
      recruitment of cortical and subcortical motor systems between groups, presumably
      reflecting age differences in motor response execution. Adults showed greater
      hippocampal activity for sequence trials, whereas children demonstrated greater
      signal during random trials. Activity in the right caudate correlated
      significantly with behavioral measures of implicit learning for both age groups,
      although adults showed greater signal change than children overall, as would be
      expected given developmental differences in sequence learning magnitude. These
      results challenge the idea of developmental invariance in implicit learning and
      instead support a view of parallel developments in implicit and explicit learning
      systems.

PMID- 15509383
TI  - An interacting systems model of infant habituation.
AB  - Habituation and related procedures are the primary behavioral tools used to
      assess perceptual and cognitive competence in early infancy. This article
      introduces a neurally constrained computational model of infant habituation. The
      model combines the two leading process theories of infant habituation into a
      single functional system that is grounded in functional brain circuitry. The HAB
      model (for Habituation, Autoassociation, and Brain) proposes that habituation
      behaviors emerge from the opponent, complementary processes of hippocampal
      selective inhibition and cortical long-term potentiation. Simulations of a
      seminal experiment by Fantz [Visual experience in infants: Decreased attention
      familiar patterns relative to novel ones. Science, 146, 668-670, 1964] are
      reported. The ability of the model to capture the fine detail of infant data
      (especially age-related changes in performance) underlines the useful
      contribution of neurocomputational models to our understanding of behavior in
      general, and of early cognition in particular.

PMID- 15509384
TI  - Asynchronies in the development of electrophysiological responses to motion and
      color.
AB  - Recent reports have documented greater plasticity in the dorsal visual stream as
      compared with the ventral visual stream. This study sought to test the hypothesis
      that this greater plasticity may be related to a more protracted period of
      development in the dorsal as compared with the ventral stream. Age-related
      effects on event-related potentials (ERPs) elicited by motion and color stimuli,
      designed to activate the two visual streams, were assessed in healthy individuals
      aged 6 years through adulthood. Although significant developmental effects were
      observed in amplitudes of ERPs to both color and motion stimuli, marked latency
      effects were observed only in response to motion. These results provide support
      for the hypothesis that the dorsal stream displays a longer developmental time
      course across the early school years than the ventral stream. Implications for
      neural and behavioral plasticity are discussed.

PMID- 15509385
TI  - Common neural basis for phoneme processing in infants and adults.
AB  - Investigating the degree of similarity between infants' and adults'
      representation of speech is critical to our understanding of infants' ability to
      acquire language. Phoneme perception plays a crucial role in language processing,
      and numerous behavioral studies have demonstrated similar capacities in infants
      and adults, but are these subserved by the same neural substrates or networks? In
      this article, we review event-related potential (ERP) results obtained in infants
      during phoneme discrimination tasks and compare them to results from the adult
      literature. The striking similarities observed both in behavior and ERPs between
      initial and mature stages suggest a continuity in processing and neural
      structure. We argue that infants have access at the beginning of life to phonemic
      representations, which are modified without training or implicit instruction, but
      by the statistical distributions of speech input in order to converge to the
      native phonemic categories.

PMID- 15509386
TI  - The development of social behavior following neonatal amygdala lesions in rhesus
      monkeys.
AB  - We examined the role of the amygdala in the development of nonhuman primate
      social behavior. Twenty-four rhesus monkeys received bilateral ibotenic acid
      lesions of either the amygdala or the hippocampus or received a sham surgical
      procedure at 2 weeks of age. Subjects were reared with their mothers and were
      provided daily access to social rearing cohorts. The subjects were weaned at 6
      months of age and then observed while paired with familiar conspecifics at 6 and
      9 months of age and with unfamiliar conspecifics at 1 year of age. The subjects
      were also observed during daily cohort socialization periods. Neither amygdala
      nor hippocampus lesions altered fundamental aspects of social behavior
      development. All subjects, regardless of lesion condition, developed a species
      typical repertoire of social behavior and displayed interest in conspecifics
      during social encounters. The amygdala lesions, however, clearly affected
      behaviors related to fear processing. The amygdala-lesioned subjects produced
      more fear behaviors during social encounters than did control or hippocampus
      lesioned subjects. Although the heightened fear response of the amygdala-lesioned
      subjects was consistent across different testing paradigms and was observed with
      both familiar and novel partners, it did not preclude social interactions. In
      fact, the amygdala-lesioned subjects displayed particular social behaviors, such
      as following, cooing, grunting, presenting to be groomed, and presenting to be
      mounted more frequently than either control or hippocampus-lesioned subjects.
      These findings are consistent with the view that the amygdala is not needed to
      develop fundamental aspects of social behavior and may be more related to the
      detection and avoidance of environmental dangers.

PMID- 15509387
TI  - Sensitive periods in the development of the brain and behavior.
AB  - Experience exerts a profound influence on the brain and, therefore, on behavior.
      When the effect of experience on the brain is particularly strong during a
      limited period in development, this period is referred to as a sensitive period.
      Such periods allow experience to instruct neural circuits to process or represent
      information in a way that is adaptive for the individual. When experience
      provides information that is essential for normal development and alters
      performance permanently, such sensitive periods are referred to as critical
      periods. Although sensitive periods are reflected in behavior, they are actually
      a property of neural circuits. Mechanisms of plasticity at the circuit level are
      discussed that have been shown to operate during sensitive periods. A hypothesis
      is proposed that experience during a sensitive period modifies the architecture
      of a circuit in fundamental ways, causing certain patterns of connectivity to
      become highly stable and, therefore, energetically preferred. Plasticity that
      occurs beyond the end of a sensitive period, which is substantial in many
      circuits, alters connectivity patterns within the architectural constraints
      established during the sensitive period. Preferences in a circuit that result
      from experience during sensitive periods are illustrated graphically as changes
      in a ''stability landscape,'' a metaphor that represents the relative
      contributions of genetic and experiential influences in shaping the information
      processing capabilities of a neural circuit. By understanding sensitive periods
      at the circuit level, as well as understanding the relationship between circuit
      properties and behavior, we gain a deeper insight into the critical role that
      experience plays in shaping the development of the brain and behavior.

PMID- 15509388
TI  - The faces of development: a review of early face processing over childhood.
AB  - The understanding of the adult proficiency in recognizing and extracting
      information from faces is still limited despite the number of studies over the
      last decade. Our knowledge on the development of these capacities is even more
      restricted, as only a handful of such studies exist. Here we present a combined
      reanalysis of four ERP studies in children from 4 to 15 years of age and adults
      (n = 424, across the studies), which investigated face processing in implicit and
      explicit tasks. We restricted these analyses to what was common across studies:
      early ERP components and upright face processing across all four studies and the
      inversion effect, investigated in three of the studies. These data demonstrated
      that processing faces implicates very rapid neural activity, even in young
      children--at the P1 component--with protracted age-related change in both P1 and
      N170, that were sensitive to the different task demands. Inversion produced
      latency and amplitude effects on the P1 from the youngest group, but on N170 only
      starting in mid childhood. These developmental data suggest that there are
      functionally different sources of the P1 and N170, related to the processing of
      different aspects of faces.

PMID- 15509389
TI  - Knowing where things are in the second year of life: implications for hippocampal
      development.
AB  - Prior data have revealed striking contrasts between 18- and 24-month-old children
      in place learning, an ability known to depend on the hippocampus (Newcombe,
      Huttenlocher, Drummey, & Wiley, 1998). The current research examined the
      development of three other basic abilities of mature spatial competence: the
      representation of multiple locations, the learning of relations among objects,
      and the recall of a single location after a substantial filled delay. Results
      indicated a transition from 18 to 24 months in all three abilities. This evidence
      supports a general transition in spatial representation that occurs towards the
      end of infancy. Existing neurobehavioral data suggest that a corresponding change
      in hippocampal functioning underlies this development.

PMID- 15509390
TI  - Language experience and the organization of brain activity to phonetically
      similar words: ERP evidence from 14- and 20-month-olds.
AB  - The ability to discriminate phonetically similar speech sounds is evident quite
      early in development. However, inexperienced word learners do not always use this
      information in processing word meanings [Stager & Werker (1997). Nature, 388, 381
      382]. The present study used event-related potentials (ERPs) to examine
      developmental changes from 14 to 20 months in brain activity important in
      processing phonetic detail in the context of meaningful words. ERPs were compared
      to three types of words: words whose meanings were known by the child (e.g.,
      ''bear''), nonsense words that differed by an initial phoneme (e.g., ''gare''),
      and nonsense words that differed from the known words by more than one phoneme
      (e.g., ''kobe''). These results supported the behavioral findings suggesting that
      inexperienced word learners do not use information about phonetic detail when
      processing word meanings. For the 14-month-olds, ERPs to known words (e.g.,
      ''bear'') differed from ERPs to phonetically dissimilar nonsense words (e.g.,
      ''kobe''), but did not differ from ERPs to phonetically similar nonsense words
      (e.g., ''gare''), suggesting that known words and similar mispronunciations were
      processed as the same word. In contrast, for experienced word learners (i. e., 20
      month-olds), ERPs to known words (e.g., ''bear'') differed from those to both
      types of nonsense words (''gare'' and ''kobe''). Changes in the lateral
      distribution of ERP differences to known and unknown (nonce) words between 14 and
      20 months replicated previous findings. The findings suggested that vocabulary
      development is an important factor in the organization of neural systems linked
      to processing phonetic detail within the context of word comprehension.

PMID- 15509403
TI  - The quest for quality in the English NHS: strategic and policy issues.

PMID- 15509391
TI  - N400-like semantic incongruity effect in 19-month-olds: processing known words in
      picture contexts.
AB  - To understand mechanisms of early language acquisition, it is important to know
      whether the child's brain acts in an adult-like manner when processing words in
      meaningful contexts. The N400, a negative component in the eventrelated potential
      (ERP) of adults, is a sensitive index of semantic processing reflecting neural
      mechanisms of semantic integration into context. In the present study, we
      investigated whether the mechanisms indexed by the N400 are already working
      during early language acquisition. While 19-month-olds were looking at
      sequentially presented pictures, they were acoustically presented with words that
      were either congruous or incongruous to the picture content. The ERP averaged
      across the group of 55 children revealed an N400-like semantic incongruity effect
      in addition to an early phonological-lexical priming effect. The results suggest
      that both lexical expectations facilitating early phonological processing and
      mechanisms of semantic priming facilitating integration into semantic context are
      already present in 19-month-olds. The child's specific comprehension abilities
      are reflected in strength, latency, and hemispheric differences of the semantic
      incongruity effect. Spatio-temporal differences in that effect, thus, indicate
      changes in the organization of brain activity correlated with the child's
      behavioral development.

PMID- 15509405
TI  - Multiple regression of cost data: use of generalised linear models.
AB  - OBJECTIVE: Choosing an appropriate method for regression analyses of cost data is
      problematic because it must focus on population means while taking into account
      the typically skewed distribution of the data. In this paper we illustrate the
      use of generalised linear models for regression analysis of cost data. METHODS:
      We consider generalised linear models with either an identity link function
      (providing additive covariate effects) or log link function (providing
      multiplicative effects), and with gaussian (normal), overdispersed poisson,
      gamma, or inverse gaussian distributions. These are applied to estimate the
      treatment effects in two randomised trials adjusted for baseline covariates.
      Criteria for choosing an appropriate model are presented. RESULTS: In both
      examples considered, the gaussian model fits poorly and other distributions are
      to be preferred. When there are variables of prognostic importance in the model,
      using different distributions can materially affect the estimates obtained; it
      may also be possible to discriminate between additive and multiplicative
      covariate effects. CONCLUSIONS: Generalised linear models are attractive for the
      regression of cost data because they provide parametric methods of analysis where
      a variety of non-normal distributions can be specified and the way covariates act
      can be altered. Unlike the use of data transformation in ordinary least-squares
      regression, generalised linear models make inferences about the mean cost
      directly.

PMID- 15509406
TI  - Increasing response rates to postal questionnaires: a randomised trial of
      variations in design.
AB  - OBJECTIVES: Low response rates to postal questionnaires can threaten the validity
      of studies by reducing the effective sample size and introducing bias. The
      identification of methods with which to optimise response rates could, therefore,
      improve the quality of studies. In an attempt to identify such methods, we
      undertook a randomised trial of two simple variations in questionnaire design.
      METHODS: Using a 2 x 2 factorial design, we conducted a randomised trial to test
      two variations in questionnaire design; the questionnaires were printed on either
      single-sided or double-sided paper and had either a single- or multiple-booklet
      layout. Using equal random allocation, 3836 women were randomised to receive one
      of these questionnaires as part of a study investigating risk factors for
      osteoporotic fractures. RESULTS: One thousand eight hundred and seventy
      questionnaires were returned, giving an overall response rate of 48.7%. There
      were no significant differences in the overall response to each of the four
      questionnaire designs. When the number of responders who completed at least 50%
      of each of the three sections was identified, it was found that single-booklet
      questionnaires had a better response than the multiple-booklet questionnaires and
      that single-sided questionnaires had a better response than double-sided
      questionnaires. However, these results were not significant at the 5% level.
      There were no significant differences in the response to questions on the odd
      (left-hand side) pages for the single- compared with the double-sided
      questionnaires. CONCLUSION: As the most cost-effective use of resources, we would
      advocate the use of double- rather than single-sided questionnaires, and use of a
      single- rather than multiple-booklet design.

PMID- 15509407
TI  - Interprofessional collaboration in the hospital: strategies and meanings.
AB  - OBJECTIVES: Interprofessional collaboration is widely advocated in health and
      social care policies. However, existing research provides a relatively poor
      understanding of how professionals collaborate or the meanings they attach to
      their collaborative work. This paper aims to contribute to understanding of this
      activity by providing an in-depth account of interprofessional collaboration on
      medical wards in a large teaching hospital. METHODS: Ethnographic methods were
      used, including individual and group interviews with health and social care staff
      (i.e. doctors, nurses, therapists, social workers; n = 49) and participant
      observations of ward-based work. RESULTS: The organisation of medical teams, who
      cared for patients across a number of wards, and the task oriented nature of
      medical work, limited opportunities for collaboration with other professionals
      (e.g. nurses, therapists) who were usually based on a single ward. Consequently,
      collaboration tended to be task-based, terse and formalistic. Staff employed a
      range of informal and formal communication strategies to overcome these
      constraints. Professionals also gave contrasting accounts of collaboration:
      doctors viewed collaboration primarily as an activity involving work with their
      medical colleagues, whereas other professionals saw it more as an
      interprofessional activity. CONCLUSIONS: Temporospatial constraints and
      contrasting notions of 'collaboration' are important factors in shaping the
      nature of interprofessional collaboration. Policies that promote this activity
      cannot assume that shared understanding of collaboration exists. They also need
      to be mindful of the practical constraints that affect collaboration in hospital
      wards.

PMID- 15509408
TI  - Do different types of nurses give different triage decisions in NHS Direct? A
      mixed methods study.
AB  - OBJECTIVES: To determine whether nurses with different clinical backgrounds make
      different triage decisions in NHS Direct, the 24-hour telephone helpline staffed
      by nurses. METHODS: Mixed methods including semistructured interviews with 24
      nurses and a multilevel analysis of 60 794 calls triaged by 296 nurses. RESULTS:
      Nurse accounts helped to identify nurse characteristics that might affect
      decision-making. The proportion of calls triaged to self-care was 40% (24 049/60
      794), varying by individual nurse from a 10th centile of 22% to a 90th centile of
      60%, after adjustment for the age and sex of the patient and the time of the
      call. Variability was partly explained by the length of clinical experience of
      nurses and the type of software used: nurses with more than 20 years clinical
      experience were more likely to triage callers to self-care than those with less
      than ten years experience (42% versus 36%, respectively; odds ratio = 1.41, 95%
      confidence interval 1.13, 1.78). Proportions triaged to selfcare differed by the
      type of clinical decision support software used: 31%, 37% and 44%. There was no
      evidence that the clinical background of nurses (hospital or community), their
      length of experience in NHS Direct, the range of their experience, or their
      gender affected triage decisions. Interviews identified that nursing
      characteristics affected individual nurses in different ways and helped to
      generate a hypothesis for future research - that individual nurses' approaches to
      risk may influence triage decisions. CONCLUSION: There is no likely benefit in
      narrowing nurse recruitment to particular clinical backgrounds. The
      appropriateness of triage decisions still needs to be evaluated.

PMID- 15509409
TI  - Estimation of numbers of British medical graduates working in the National Health
      Service: comparison of capture-recapture analysis and exhaustive tracing.
AB  - OBJECTIVE: To compare the results of capture-recapture estimates and exhaustive
      follow-up in identifying the percentage of UK medical graduates who subsequently
      worked in the British National Health Service (NHS). METHODS: Postal
      questionnaire survey of all UK-trained doctors who graduated in 1974, with up to
      three reminders sent to non-respondents. Further exhaustive tracing of non
      respondents to obtain whole population estimates of numbers in the NHS. Capture
      recapture estimation of numbers working in the NHS, using survey data and
      Department of Health employment records, for comparison with results from
      exhaustive tracing. RESULTS: A total of 85.3% (1460/1712) of respondents were
      working in the NHS, but further exhaustive tracing of non-respondents revealed
      that only 75.9% (1758/2317) to 79.2% (1835/2317) of the whole cohort were in the
      NHS. By comparison, capture-recapture analysis estimated that 76.9% (1781/2317)
      of the cohort were in the NHS (95% CI: 75.9% to 78.0%). CONCLUSIONS: Survey data
      alone overestimated the percentage of the whole cohort in the NHS. Capture
      recapture estimates were very similar to those obtained by exhaustive tracing but
      were obtained more quickly and for much less clerical effort.

PMID- 15509410
TI  - Health care resource allocation: is the threshold rule good enough?
AB  - We review the foundations of resource allocation rules based on cost
      effectiveness information. Comprehensive approaches, where a total budget is
      allocated in one go, require estimation of the costs and effects of all available
      health care programmes, which is unlikely to be practical. A common alternative
      is to assess individual programmes against a cost-effectiveness threshold. This
      has been shown to be efficient if the threshold is well calibrated and all
      programmes can be wholly or partially implemented with constant returns to scale.
      We discuss the feasibility of these assumptions, and the effects of relaxing
      them, concluding that programme indivisibility is unlikely to be a serious
      problem at a national level, but that miscalibration of the threshold and non
      constant returns to scale might be. A rule that avoids these difficulties has
      been proposed previously: a new programme should only be implemented if it can be
      funded by cancelling another less effective programme. This could never reduce
      efficiency, unlike the threshold rule, though we show that it might sometimes
      fail to recommend an efficiency-improving change. We suggest a refinement of this
      reallocation rule based on explicit estimation of the costs and effects of
      partial implementation of the programmes under review. Research is required to
      assess the practicality of this option.

PMID- 15509411
TI  - Assessing health quality: the case for tracers.

PMID- 15509412
TI  - Does medical culture limit doctors' adoption of quality improvement? Lessons from
      Camelot.
AB  - This paper analyses aspects of medical culture, explains why this culture is
      antagonistic to quality improvement, and provides solutions to help medical
      colleges meet the challenge of clinical governance. Like the knights of Camelot,
      doctors have their own all-pervading culture, occupationally centred, exclusive
      to the initiated and tending to the traditional, either overtly or through
      assumed values. The Camelot metaphor is supported by analysis of empirical
      evidence, especially the documents produced by medical colleges. Suggested
      initiatives to overcome these organisational barriers include improvements in
      continuing medical education, accreditation, guideline production and
      responsibility for the performance of doctors. Central to these improvements
      should be the involvement of every doctor, via the Delphi process, and
      substantial contributions to college processes from other health care professions
      and patients.

PMID- 15509414
TI  - The cost of dying is an increasing strain on the health care system.

PMID- 15509416
TI  - 8th Biennial Conference of the International Endotoxin Society, Kyoto, Japan,
      November 15-18, 2004. Abstracts.

PMID- 15509420
TI  - Efficacies of chloroquine, sulfadoxine-pyrimethamine and quinine in the treatment
      of uncomplicated, Plasmodium falciparum malaria in eastern Sudan.
AB  - The efficacies of several antimalarial drugs in the treatment of uncomplicated
      Plasmodium falciparum malaria were compared, during an open, randomized trial, in
      New Halfa, eastern Sudan. The 96 patients who completed the 28 days of follow-up
      were treated with chloroquine (N = 26), sulfadoxine-pyrimethamine (N = 38) or
      quinine (N = 32). No treatment failures were observed among the patients given
      sulfadoxine-pyrimethamine. Only 23.1% of the patients given chloroquine showed
      adequate clinical response, however, the rest showing early (15.4%) or, more
      frequently, late (61.5%) treatment failure. In terms of parasitological failure,
      54.1% of the patients given chloroquine showed early RI resistance, 7.7% showed
      late RI, and 15.1% showed RIII. Most (90.6%) of the patients treated with quinine
      had adequate treatment responses, the rest having late treatment failures (and
      late RI). The frequency of treatment failure was significantly higher, however,
      among the patients given chloroquine than in the quinine-treatment arm. The
      present results and those of earlier investigations indicate that the problem of
      chloroquine resistance is worsening in eastern Sudan, and that the use of
      chloroquine as the first-line drug for the treatment of uncomplicated malaria in
      this area is now compromised. The response to quinine may also be faltering.

PMID- 15509421
TI  - Diagnosis of visceral leishmaniasis: the sensitivities and specificities of
      traditional methods and a nested PCR assay.
AB  - In the present study, 67 patients suspected to be cases of visceral leishmaniasis
      (VL) were each checked for leishmanial infection by the microscopical evaluation
      of various biological specimens, in-vitro culture, serology and an assay based on
      nested PCR. Most (35) of the subjects were immunocompetent (IC) but 32 were
      immunodeficient (ID) as the result of HIV infection (18 cases), treatment to
      prevent transplanted organs being rejected (six) or haematological malignancies
      (eight). Forty-one (61.2%) of the subjects (19 IC subjects, 12 HIV-positive
      patients, four transplant patients and six patients with malignancies) were
      considered true cases of VL. For the IC subjects, only the production and
      microscopical examination of leucocytoconcentrates and cultures of Buffy coats
      gave sensitivities of <80%, the results of the other methods showing higher
      sensitivities and almost perfect agreement with the 'gold-standard' diagnoses.
      For the ID subjects, however, only the serological tests and the PCR gave
      reasonable sensitivities (of >80%). For the initial diagnosis of leishmaniasis in
      ID patients, IFAT and western blots may be useful, as, among the present ID
      patients, they gave sensitivities (of 80.9% and 88.2%, respectively) that were
      almost as high as that for the PCR, and specificities of 100%. In the diagnosis
      of VL in either IC or ID patients, the assay based on a nested PCR appeared to be
      particularly reliable, with sensitivities of 88.9% and 95.2%, respectively, and a
      specificity of 100% in both groups of patients. The testing of bone-marrow
      aspirates by PCR revealed very few VL cases who were not found positive when
      samples of their peripheral blood were checked in the same assay. For both IC and
      ID subjects therefore, the use of the PCR-based method to test samples of
      peripheral blood (which can be collected much more easily than bone-marrow
      aspirates and with much less pain for the subject) is recommended.

PMID- 15509422
TI  - Identification of Leishmania strains from Jordan.
AB  - The enzymatic profiles of 22 Jordanian Leishmania isolates obtained from humans,
      Psammomys obesus and Phlebotomus papatasi were determined using starch-gel
      electrophoresis and a 15-enzyme system. Thirteen of the isolates were typed as L.
      major and the other nine, all from Mediterranean or sub-Mediterranean regions, as
      L. tropica. The two zymodemes of L. major encountered, MON-26 and MON-103,
      differed in terms of purine nucleoside phosphorylase 2. The MON-26 isolates came
      from the Jordanian plateau whereas those of MON-103 were only collected from the
      Jordan valley. The four zymodemes of L. tropica observed (MON-7, MON-137, MON-200
      and MON-265) were identical for only two of the 15 enzymes studied (i.e.
      isocitrate dehydrogenase and glucose phosphate isomerase), confirming the high
      level of enzymatic polymorphism of L. tropica. So far, MON-200 and MON-265 have
      only been found in Jordan.

PMID- 15509423
TI  - Missed treatment opportunities, for pregnant and breast-feeding women, in
      onchocerciasis mass-treatment programmes in south-eastern Nigeria.
AB  - During annual rounds of mass treatment against onchocerciasis, women who are
      pregnant or nursing neonates should not to be offered ivermectin. The aim of the
      present study was to determine how many women were not treated, as a result of
      this policy, in four villages in south-eastern Nigeria. Of the 1714 women of
      reproductive age present during the 2000 round of mass treatment, 599 (35%) were
      excluded because they were pregnant or nursing babies aged < 1 month. Most (56%)
      of the 599 excluded women were, however, treated individually later in the year.
      Of the 264 excluded women who did not receive a dose of ivermectin at all in
      2000, 123 (47%) said they would have actively sought ivermectin treatment had
      they been made aware of the short duration of exclusion for nursing. If they had
      all known of the short duration of the exclusion and when and how to locate and
      receive treatment in their villages after the round of mass treatment, 91% of the
      women excluded from the round of mass treatment would probably have been treated
      later in the year. Better treatment systems, follow-up and health education,
      targeted at pregnant and lactating women, would improve treatment coverage of
      this group after parturition and early nursing.

PMID- 15509424
TI  - Factors associated with participation in a campaign of mass treatment against
      lymphatic filariasis, in Leogane, Haiti.
AB  - In October 2000, to interrupt transmission of Wuchereria bancrofti, an intense
      health-education campaign followed by a mass drug administration (MDA) with
      diethylcarbamazine and albendazole was undertaken in Leogane, Haiti. Three months
      after the MDA, which was the first in the study area, a knowledge-attitude
      practice (KAP) survey, with a cluster-sample design and probability sampling, was
      undertaken, to determine the existing knowledge of the local residents, their
      attitudes toward the MDA, and the possible reasons for non-compliance.
      Questionnaire-based interviews were used to explore the KAP of 304 subjects (one
      randomly chosen resident aged > 14 years from each selected household) in 33
      communities. Most (93%) of the interviewees were aware of filariasis and 72% knew
      at least one clinical sign of the disease. Awareness of the MDA was high (91%).
      The most frequently mentioned sources of information were other people (56%) and
      radio announcements (33%). More than 80% of the respondents encouraged other
      people to take the drugs distributed in the MDA and 63% had been treated. The
      primary reasons given for failing to take the drugs were absenteeism during the
      distribution (17%), use of contraceptive drugs (12%) and pregnancy (11%). In a
      multivariate analysis, being male [odds ratio (OR) = 3.3; 95% confidence interval
      (CI) = 1.5-7.4], knowing that a mosquito transmits the disease (OR = 2.6; CI =
      1.2-5.4), and having learned about the MDA through posters and banners (OR = 2.9;
      CI = 1.2-7.5) were found to be positively associated with taking the drugs.
      Information from such post-treatment surveys should be useful in developing
      better health communication for subsequent MDA.

PMID- 15509425
TI  - Induction of matrix metalloproteinase-9 in murine eosinophilic meningitis caused
      by Angiostrongylus cantonensis.
AB  - Matrix metalloproteinases (MMP) have been implicated in the pathogenesis of
      various inflammatory diseases of the central nervous system. In the present
      study, a gelatinase was found to be induced in parasitic meningitis caused, in
      mice, by Angiostrongylus cantonensis. The enzyme had a molecular weight of about
      94 kDa, showed maximal activity between pH 6 and pH 8, and was clearly inhibited
      by EDTA and 1,10-phenanthroline but not by leupeptin or phenylmethanesulphonyl
      fluoride. When samples of cerebrospinal fluid from the mice with meningitis were
      blotted with specific antiserum against gelatinase B (MMP-9), a 94-kDa
      immunopositive band was observed, indicating that the induced gelatinase was MMP
      9. In the A. cantonensis-infected mice, immuno-histochemistry demonstrated MMP-9
      within the endothelial cells lining the vascular spaces of the brain and in the
      leucocytes that were found, in aggregates, in the subarachnoid space. Leucocytes
      may play an important role in the pathogenesis of inflammatory disorders of the
      central nervous system.

PMID- 15509426
TI  - Porcine and rodent infection with Trichinella, in the Sierra Grande area of Rio
      Negro province, Argentina.
AB  - In 2000, two cases of human trichinellosis were detected in the Sierra Grande
      area of Rio Negro province, Argentina. As part of an investigation of the
      aetiology of these cases, 300 pigs slaughtered for consumption in the area
      between 2000 and 2002 were checked for Trichinella infection, by artificial
      digestion of a muscle sample. Twelve (5.6%) - four (7.3%) of the 55 checked in
      2000, five (4.8%) of the 105 investigated in 2001, and three (2.1%) of the 140
      investigated in 2002 - were found infected. Blood samples were collected from
      other pigs aged > 6 months old, so that sera could be tested, in ELISA and by
      western blotting, for anti- Trichinella antibodies. Of the 181 animals checked in
      the initial serological survey, 36 (19.9%) were found seropositive for
      Trichinella. When 35 of the seronegative pigs were re-checked 6 months later,
      three (8.6%) were found to have seroconverted. Four (15.4%) of 26 local rodents,
      caught in Sherman-type traps, were also found positive when checked for infection
      by artificial digestion. It appears that about 20% of pigs in the study area are
      infected each year, this high level of transmission being sustained by a high
      prevalence of infection in the local rodent populations.

PMID- 15509428
TI  - The sandflies (Diptera: Psychodidae) in the Turkish province of Hatay: some
      possible vectors of the parasites causing human cutaneous leishmaniasis.
AB  - The province of Hatay, which lies on the Mediterranean coast in south-eastern
      Turkey, forms an important endemic area for human cutaneous leishmaniasis (HCL).
      Between the June and November of 2001, the sandflies in eight areas of the
      province, Erzin, Dortyol, Iskenderun, Kirikhan, Antakya, Samandag, Altinozu and
      Yayladagi, were surveyed, using sticky-paper traps placed in goat, sheep, cow or
      chicken sheds close to houses. Although 217 of the 998 sandflies caught belonged
      to the genus Sergentomyia, the rest were of Phlebotomus species, including some
      species that, elsewhere, are known to act as vectors of the parasites causing
      HCL. The Sergentomyia caught were either S. theodori (59.9%) or S. dentata
      (40.1%). Most of the Phlebotomus were P. sergenti (60.8%) but P. papatasi
      (18.8%), P. syriacus (9.3%), P. neglectus (5.1%), P. tobbi (2.7%), P. simici
      (2.2%), P. alexandri (0.9%) and P. kyreniae (0.1%) were also identified (the
      latter three species for the first time in Hatay province). The identification of
      the main vector species of sandfly in the province is complicated because it is
      still uncertain which Leishmania species cause(s) the local HCL. It seems likely,
      however, that P. sergenti is the main vector in Antakya, Iskenderun, Dortyol,
      Erzin and Kirikhan. In areas such as Altinozu and Yayladagi, where, although P.
      sergenti is very rare or absent, HCL cases still occur each year, other species,
      such as the relatively abundant P. papatasi and P. syriacus, may be the main
      vectors.

PMID- 15509427
TI  - Cytotoxic and antimicrobial coumarins from Mammea africana.
AB  - Six coumarin derivatives [three 4-phenylcoumarins (Mammea A/AA, Mammea A/BA and
      MAB 3), two 4-n-propylcoumarins (Mammea B/BB and Mammea B/BA) and one 4-n
      pentylcoumarin (Mammea C/OB)], 1,5-dihydroxyxanthone and 1-methoxy-5
      hydroxyxanthone have been isolated from the stem bark of Mammea africana Sabine
      collected in Cameroon. Although known, the structures of the coumarin derivatives
      were confirmed by spectral analysis, including two-dimensional nuclear magnetic
      resonance. All the coumarin compounds showed noteworthy cytotoxicity against the
      human 9-KB cell line. Both of the 4-n-propylcoumarins were also found to exhibit
      significant activity against Staphylococcus aureus.

PMID- 15509429
TI  - The programme to eliminate lymphatic filariasis in Orissa, India: the attitudes
      of some programme partners.

PMID- 15509430
TI  - Dengue fever is a differential diagnosis in patients with fever and abdominal
      pain in an endemic area.

PMID- 15509431
TI  - Ten years on--past perfect, future bright.

PMID- 15509433
TI  - Primary Dental Care 1994-2004: the first ten years. Chronicles of a new journal.

PMID- 15509435
TI  - Primary Dental Care 1994-2004: the first ten years. A chronology.
AB  - The prime purpose of a professional journal is to keep its readers informed of
      changes of importance affecting the practise of that profession. That is the
      criterion that I have applied in producing this chronology of the papers that
      have been published in Primary DENTAL CARE during the past decade. The ambition
      which has guided me since I received the invitation to carry out this review is a
      simple one: to include as much as may generally be found useful by general dental
      practitioners (GDPs), who form the bulk of our readership. In 1789 the English
      philosopher Jeremy Bentham extolled the virtues of utility for mankind when he
      declared that 'the greatest happiness of the greatest number is the foundation of
      morals and legislation'. The contributors that I have included, by contrast,
      think of their utilitarianism as striving after the most practical. The principal
      purpose of this chronology is to achieve a summary, without weighing causes or
      consequences. From past experience, an outstanding virtue of such an aggregated
      record is that it can inspire fresh patterns of thought and thus encourage the
      submission of manuscripts as a result of those thoughts. I can think of scarcely
      any facet of the general practice of dentistry that has not been touched upon,
      for the most part authoritatively. I hope that these brief aide-memoires may
      persuade old readers to return to those articles of particular interest to them
      and that new readers will feel informed about past papers. Every issue of the
      journal to date has been reviewed. Dates, volume and issue numbers and principal
      authors' names are all included. With these identifying features any paper, to
      which reference is made, may be quickly found. It would be manifestly absurd to
      use precious space on a formal listing of more than 250 references and this
      listing has, therefore, been omitted.

PMID- 15509436
TI  - The clinical innovations conference.
AB  - At the end of May, an impressive team of speakers from North America and the
      United Kingdom provided two days of lectures and hands-on sessions that updated
      delegates on practice management, team dentistry, fixed and removable
      prosthodontics, endodontics and implantology, with the emphasis on new materials
      and techniques.

PMID- 15509437
TI  - An interview with the Chief Dental Officer. Interview by Kenneth A. Eaton.
AB  - Some months ago, I mentioned to Professor Raman Bedi, the Chief Dental Officer
      (CDO) for England, that Primary DENTAL CARE would be celebrating its tenth
      anniversary in October 2004. He kindly agreed to a special interview during which
      he would outline his vision for education, research and opportunities for career
      development in primary dental care in the future. The timing proved to be perfect
      as earlier on the day of the interview (16th July 2004), the Secretary of State
      for Health, John Reid, announced the Government's plans for NHS dentistry and NHS
      Dentistry: Delivering Change. Report from the Chief Dental Officer (England) 2004
      was published.

PMID- 15509438
TI  - Generalised hypercementosis: a case report.
AB  - The following case report describes the clinical and radiographical presentation
      of a female who attended a general dental practice as a new patient. The patient
      was diagnosed with generalised hypercementosis, possibly attributable to oral
      neglect. Hypercementosis is associated with a number of aetiological factors,
      which may be local or systemic in nature. It is important that the general dental
      practitioner is aware of these factors and is able to distinguish presentation
      due to a local cause from that of a systemic disease process. The aims of this
      paper are to illustrate an unusual presentation of hypercementosis and to discuss
      the radiographic differentiation that led to diagnosis.

PMID- 15509439
TI  - News from the dental houses.

PMID- 15509440
TI  - Changes in self-reported attendance of British adults for dental check-ups
      between 1991 and 2000.
AB  - OBJECTIVE: To report the changes in self-reported dental check-up patterns of
      British adults in both the NHS and non-NHS sectors over the period 1991 to 2000.
      METHOD: Longitudinal cross-sectional questionnaire. RESULTS: Between 1991 and
      2000, the annual British House-hold Panel Survey (BHPS) indicated that there was
      a steady increase in the percentage of adults who reported having a dental check
      up within the previous 12 months, from 53.6% to 62.3%. While the percentage
      reporting having had a dental check-up under NHS arrangements rose slightly from
      44% to 46%, reported non-NHS check-ups rose from 6% to 14%. Variations in
      reported attendance patterns for check-ups were noted between the sexes and age
      groups. A higher percentage of females reported having had a dental check-up
      under NHS arrangements than males, while no differences were found in the non-NHS
      sector. Those aged between 46-55 years had the highest percentage of dental check
      ups (72%) while the lowest was in those aged 66 years or older (43%).
      CONCLUSIONS: The results of the BHPS indicate that there was an increase in the
      percentage of British adults attending for a dental check-up within any 12-month
      period for 1991 to 2000 and that there was considerable variation in attendance
      by both age and sex.

PMID- 15509443
TI  - Neurosyphilis.
AB  - Treponema pallidum, the bacterium that causes syphilis, invades the central
      nervous system early in the course of disease but causes persistent infection in
      only a subset of infected persons. Individuals with persistent infection or
      asymptomatic meningitis are at risk for developing symptomatic neurosyphilis if
      they are not treated with a drug regimen that achieves sufficient drug levels in
      cerebrospinal fluid to kill the organism. In this article, recent studies that
      address the risk, diagnosis, and management of neurosyphilis are discussed within
      the context of a brief review. Particular attention is given to current
      controversies. In the developed world, these issues are particularly relevant to
      persons who are infected with HIV.

PMID- 15509444
TI  - Neurosarcoidosis.
AB  - Neurosarcoidosis is an uncommon presentation of sarcoidosis. It is associated
      with significant morbidity and poor outcome. In the past decade, there has been
      significant progress in our understanding of the immunopathogenesis of the
      disease, but the etiology of this enigmatic condition still eludes us. Improved
      insight has paved the way for development of different treatment strategies
      against critical immunologic stages of the disease.

PMID- 15509445
TI  - Diagnosis and management of brain abscess and subdural empyema.
AB  - Advances in the diagnosis and treatment of brain abscess and subdural empyema
      with neuroimaging techniques such as computerized tomography, magnetic resonance
      imaging, magnetic resonance spectroscopy, the availability of new antimicrobials,
      and the development of novel surgical techniques have significantly contributed
      to the decreased morbidity and mortality associated these infections.
      Determination of point of entry and source of infection is paramount to adequate
      treatment. A high index of suspicion along with typical clinical presentation of
      headache, seizures, or focal neurologic signs can lead to early diagnosis so that
      effective therapy can be instituted as soon as possible. This review discusses
      etiology and pathology of brain abscess and subdural empyema, neuroimaging
      techniques useful in the diagnosis, and optimal treatment, including use of
      antimicrobials and surgical procedures.

PMID- 15509447
TI  - Neural mechanisms of semantic memory.
AB  - Using previously published functional magnetic resonance imaging work studying
      object recall as a framework, we describe the spatial and temporal properties of
      brain activation as one plausible model of visually triggered access to semantic
      memory. We suggest that interactions between the dorsomedial thalamus and
      Brodmann area 6 facilitate the setting of object search criteria and perhaps
      drive the search. The pulvinar nucleus of the thalamus, in concert with ventral
      temporal and occipital cortical regions, become active later, perhaps when the
      criteria are met or the target object is identified.

PMID- 15509448
TI  - Event-related brain potential studies in language.
AB  - A review of the four relevant language-related components in event-related brain
      potentials (ERPs) is provided. The different ERP components are functionally
      specified: the N400 component reflects semantic processes, the ELAN reflects
      early syntactic processes, the P600 reflects late syntactic reanalysis, and the
      CPS reflects aspects of prosodic processing. The neural generators of these
      components are discussed as well, both in the context of available brain imaging
      data and ERPs from lesion patient studies.

PMID- 15509449
TI  - Apraxia.
AB  - In this review, we present a summary of some of the most pertinent new research
      on aspects of apraxia. Rather than attempt a review of all neurologic syndromes
      that have been identified as forms of apraxia, such as buccofacial, truncal,
      apraxia of eye opening, and apraxia of speech, we focus on current literature and
      trends in the study of limb apraxia. Although the classic empirical approach to
      the study of apraxia has been through systematic neuropsychologic assessment of
      various aspects of the syndrome, questions remain regarding the exact neural
      substrate that forms the foundation of the praxis system. More recent work using
      sophisticated neuroimaging methods has yielded a wealth of new data that
      contributes significantly to our understanding of the neuroanatomic correlates of
      this complex disorder. In addition, the results of recent sophisticated
      neuropsychologic studies have suggested modifications to classic cognitive models
      of apraxia. A discussion of current work and directions for future research are
      also provided.

PMID- 15509451
TI  - Critical care of neurotrauma.
AB  - Traumatic brain injury often affects people in their most productive years,
      inflicting a significant burden on families and society. The advances in modern
      critical care have improved survival of patients; thus more patients live after
      traumatic brain injury, which raises an important issue about their neurologic
      outcome. At the present time, there are limited data regarding methods to
      optimize neurologic recovery. In this review, we try to bring information from
      different sources to show new approaches to achieve that goal. Some of the
      techniques employed are investigational and some are waiting to find broader
      application in intensive care units across the country.

PMID- 15509452
TI  - Management of seizures in critically ill patients.
AB  - For many neurologists, seizures in critically ill patients represent a difficult
      problem. Etiology can be elusive because of the complexity of the environment,
      and treatment decisions can be compromised by the paucity of evidence-based
      guidelines. Emerging data support a higher than previously thought incidence of
      nonconvulsive epileptic activity in this patient population, which is another
      important consideration. Although a seizure in the intensive care unit should be
      treated aggressively, prophylactic antiepileptic drug administration is dependent
      on the specific etiology, time of onset, and ensuing complications. After
      ischemic stroke, prophylactic treatment is not generally recommended, and after
      intracerebral hemorrhage treatment is recommended only after a few weeks. After
      subarachnoid hemorrhage, prophylactic treatment beyond discharge is also not
      recommended. Although there is no reason to believe that late seizures after
      severe head trauma cannot be prevented with prophylactic treatment, such an
      approach may be useful during the first week after the injury. Physicians,
      however, have to individualize the treatment to the critical patient after stroke
      or trauma based on the presence of additional factors that increase the risk for
      seizures, including structural cortical injuries and medications used in critical
      illness with epileptogenic potential. A general therapeutic scheme for seizures
      in the intensive care unit and the role newer antiepileptic drugs can play are
      also presented in this review.

PMID- 15509453
TI  - Management of massive cerebral infarct.
AB  - Patients with large hemispheric strokes frequently develop neurologic
      deterioration secondary to cerebral edema. Regardless of the medical and surgical
      management of cerebral edema, there is high morbidity and mortality. This article
      reviews the clinical and radiographic features of large hemispheric strokes and
      examines the various therapeutic options for management of cerebral edema.

PMID- 15509454
TI  - What do we (not) know about the management of blood pressure in acute stroke?
AB  - Although it is indisputable that high blood pressure should be treated to prevent
      a first or a recurrent stroke, the management of high blood pressure in the first
      hours and days after stroke remains controversial. There is no high-quality
      evidence from randomized controlled trials to guide treatment in the 80% of
      patients who have elevated blood pressure during the first days after stroke.
      Theoretically, there are pros and cons for manipulating blood pressure after
      onset of stroke. Most treatment guidelines suggest leaving blood pressure
      untouched based on pathophysiologic principles. Post-hoc analyses from randomized
      trials, however, suggest that elevated blood pressure is associated with
      recurrent stroke and higher mortality, even after adjustment for potential
      confounders. On the other hand, preliminary studies have suggested that
      voluntarily increasing blood pressure might be beneficial in a selected subgroup
      of patients. In this overview, we present a summary of recent studies on this
      topic.

PMID- 15509455
TI  - Biologic poisons for pain.
AB  - Pain therapies from natural sources date back thousands of years to the use of
      plant and animal extracts for a variety of painful conditions and injuries. We
      certainly are all familiar with modern uses of plant-derived analgesic compounds
      such as opium derivatives from papaverum somniferum and salicylates from willow
      bark (Salix species). Local anesthetics were isolated from coca leaves in the
      late 1800s. Sarapin, derived from carnivorous pitcher plants, has been injected
      for regional analgesia in human and veterinary medicine, but efficacy is
      controversial. Biologic organisms can play important roles in developing an
      understanding of pain mechanisms, either from isolation of compounds that are
      analgesic or of compounds that produce pain, hyperalgesia, and allodynia.

PMID- 15509456
TI  - Prioritizing treatment attributes and their impact on selecting an oral triptan:
      results from the TRIPSTAR Project.
AB  - Seven oral triptans, which differ on a range of attributes important for
      treatment selection, are now available for treating migraine. US neurologists
      were surveyed to assess the relative importance of treatment attributes,
      prespecified by clinical relevance and availability of controlled study data, for
      selecting among oral triptans. Using a multiattribute decision model, we combined
      these data on the importance of treatment attributes with information on the
      relative performance of the oral triptans derived from a recent meta-analysis of
      controlled clinical trials.

PMID- 15509457
TI  - Urologic myofascial pain syndromes.
AB  - Treatment of pain of urogenital origin, chronic pelvic pain syndrome, can be
      frustrating for patients and physicians. The usual approaches do not always
      produce the desired results. Visceral pain from pelvic organs and myofascial pain
      from muscle trigger points share common characteristics. Referred pain from
      myofascial trigger points can mimic visceral pain syndromes and visceral pain
      syndromes can induce trigger point development and myofascial pain and
      dysfunction. The referred pain syndrome can long outlast the initial event,
      making diagnosis difficult.

PMID- 15509458
TI  - Myofascial dysfunction in the pelvis.
AB  - Chronic pelvic pain is a potentially devastating condition that affects many
      women with severe consequences. A multifaceted condition, chronic pelvic pain
      enjoys a diverse etiology, a myriad of treatments, and a correspondingly
      irregular response to therapy. The condition can be associated with severe
      physical dysfunction in relation to voiding, defecation, and sexual function.
      Although emphasis has been placed on surgical approaches to therapy, there is
      increasing interest in alternative therapies, particularly using the principles
      of the treatment of myofascial dysfunction.

PMID- 15509459
TI  - Otolaryngic myofascial pain syndromes.
AB  - It has been long recognized in the otolaryngic community that despite great
      effort dedicated to the physiology and pathology of the ear, nose, throat/head
      and neck, there are a number of symptoms, including pain in various locations
      about the head and neck, which cannot be explained by traditional otolaryngic
      principles. The tenets of myofascial dysfunction, however, as elucidated by Dr.
      Janet Travell, explain most of these previously unexplained symptoms;
      furthermore, treatment based on Dr. Travell's teachings is effective in relieving
      these symptoms.

PMID- 15509460
TI  - Myofascial pain: diagnosis and management.
AB  - Clinical understanding and management of myofascial pain is overlooked frequently
      when dealing with pain. Myofascial pain is defined as pain or autonomic phenomena
      referred from active trigger points, with associated dysfunction. The trigger
      point is a focus of hyperirritability in the muscle that, when compressed, is
      locally tender and, if sensitized, gives rise to referred pain and tenderness.
      The pain quality is dull or achy and associated with autonomic changes.
      Myofascial pain is poorly understood, which results too often in underdiagnosis
      and poor management. The pathogenesis likely has a central mechanism with
      peripheral clinical manifestations. The therapy for myofascial pain requires
      enhancing central inhibition through pharmacology or behavioral techniques and
      simultaneously reducing peripheral inputs through physical therapies including
      exercises and trigger point-specific therapy.

PMID- 15509461
TI  - An expansion of Simons' integrated hypothesis of trigger point formation.
AB  - Simons' integrated hypothesis proposed a model of trigger point (TrP) activation
      to explain known TrP phenomena, particularly endplate noise. We propose an
      expansion of this hypothesis to account for new experimental data and established
      muscle pathophysiology.

PMID- 15509462
TI  - The tension headache component of chronic daily headache.
AB  - Chronic daily headache (CDH) is an overarching term that includes multiple types
      of frequent primary headaches that are not trigeminal-autonomic cephalgias. The
      components of typical CDH can be divided into a more severe or "big" headache and
      a less severe or "little" headache. The big headaches tend to have features of
      migraine while the little headaches have features of tension-type headache (TTH).
      Whether this represents a spectrum or continuum or whether it is the
      superimposition of two unique headache entities is open to debate. For subjects
      with big and little headache, the concept that the TTH component is part of a
      spectrum seems likely. Subjects with only TTH and no migrainous component seem to
      represent a different entity, pure chronic TTH. These patients have a daily
      moderate headache that is poorly responsive to current therapies and appears to
      be a different TTH than the migraine tension type of CDH. The TTH component of
      CDH may represent multiple subdivisions of TTH.

PMID- 15509463
TI  - Alternative therapies for tension-type headache.
AB  - Treatment of tension-type headache remains very challenging. In addition to
      conventional therapies, alternative methods such as physical therapy,
      acupuncture, and botulinum toxin have been studied. In this article, recent
      literature is reviewed and discussed and challenges for the evaluation of these
      approaches are considered. Although the clinical evidence is still incomplete,
      certain treatments are promising and the active ongoing research hopefully will
      soon yield more answers. Of note, the specific issue of psychologic therapy is
      dealt with elsewhere in this issue.

PMID- 15509464
TI  - Behavioral interventions for tension-type headache: overview of current therapies
      and recommendation for a self-management model for chronic headache.
AB  - Behavioral treatments (relaxation, biofeedback, cognitive-behavioral therapy)
      have been empirically validated for migraine and tension-type headaches, with
      recent meta-analyses yielding 37% to 50% reductions in tension-type headache,
      comparing favorably with 33% reduction from medication prophylaxis
      (amitriptyline). Research has moved toward increasing availability and cost
      effectiveness through alternative delivery formats and combining and comparing
      them with standard medications. Further modifications would make standard
      behavioral treatments available and conducive to primary care settings where most
      patients receive treatment. Beyond the current behavioral and drug treatments, we
      propose a fundamental shift in conceptualization and treatment for headache.

PMID- 15509465
TI  - Tension-type headache in children and adolescents.
AB  - Although tension-type headache is at least as prevalent as migraine in children
      and adolescents, in contrast to migraine, childhood tension-type headache has
      received limited research attention. Follow-up studies have shown that migraine
      may reverse in tension-type headache and vice versa. In addition, children with
      frequent episodic tension-type headache may be at increased risk of chronic
      tension-type headache. It is very important to recognize these children and to
      intervene. Further studies are needed to clarify the pathophysiology of pediatric
      tension-type headache.

PMID- 15509466
TI  - The use of glucosamine therapy in osteoarthritis.
AB  - Glucosamine products have been used extensively for the management of pain in
      osteoarthritis. This paper reviews the most recent clinical and experimental
      studies regarding its efficacy and safety. Although clinical trials include
      methodologic flaws and publication bias, glucosamine is likely an effective
      therapy for the symptomatic management of osteoarthritis. In turn, definite proof
      for chondromodulating effect requires well-conducted clinical trials. In North
      America, glucosamine is an over-the-counter dietary supplement and preparations
      made by different manufacturers may vary. There is also a need to standardize
      this therapy and allow practitioners to give patients suitable advice. An ongoing
      long-term clinical trial in the US will possibly permit to investigate the
      clinical relevance of these results and give appropriate recommendations.

PMID- 15509467
TI  - Does osteoarthritis of the lumbar spine cause chronic low back pain?
AB  - The lumbar spine is a common location for osteoarthritis. The axial skeleton
      demonstrates the same classic alterations of cartilage loss, joint instability,
      and osteophytosis characteristic of symptomatic disease in the appendages.
      Despite these similarities, questions remain regarding the lumbar spine facet
      joints as a source of chronic back pain. The facet joints undergo a progression
      of degeneration that may result in pain. The facet joints have sensory input from
      two spinal levels that makes localization of pain difficult. Radiographic studies
      describe intervertebral disc abnormalities in asymptomatic individuals that are
      associated with, but not synonymous for, osteoarthritis. Patients who do not have
      osteoarthritis of the facet joints on magnetic resonance scan do not have back
      pain. Single photon emission computed tomography scans of the axial skeleton are
      able to identify painful facet joints with increased activity that may be helped
      by local anesthetic injections. Low back pain is responsive to therapies that are
      effective for osteoarthritis in other locations. Osteoarthritis of the lumbar
      spine does cause low back pain.

PMID- 15509468
TI  - The management of pain in arthritis and the use of cyclooxygenase-2 inhibitors:
      new paradigms and insights.
AB  - Chronic pain from arthritis has been one of the biggest causes of disability and
      loss of function in the United States. This is still the case despite many new
      insights into the pathophysiology of pain, effective treatment approaches, and
      new safer medications that can be used for long-term use. There are many
      different types of arthritic problems. New disease- modifying agents that are
      available for some of these types of arthritic diseases such as rheumatoid
      arthritis have the potential to have a substantial impact on improvement in the
      long-term prognosis. Despite this optimistic outlook, pain often is a significant
      problem and should be treated whenever it becomes a barrier to function.

PMID- 15509469
TI  - Does cold air damage the lungs of winter athletes?

PMID- 15509470
TI  - Overuse injuries in equestrian athletes.
AB  - Some 30 million Americans are involved in equestrian sports. Although there is
      significant literature regarding catastrophic injury, there is very little
      literature that addresses overuse injury and its effect on rider and horse. As
      the horse and rider function as a unit, overuse injuries to the rider can affect
      the horse's training and responsiveness. Sports physicians treating riders should
      understand correct posture in the saddle and its alteration by muscular imbalance
      and injury. This review discusses common equestrian events, and common overuse
      injuries in recreational and competitive riders.

PMID- 15509471
TI  - The athlete with fatigue.
AB  - Fatigue is a common presenting complaint in primary care offices. Nearly everyone
      experiences fatigue at one time or another, typically caused by overexertion or
      lack of sleep. Fatigue in the athlete is problematic as it may affect training
      and competitive performance. The possible causes of fatigue are widely varied,
      and the workup of fatigue can be very frustrating for the patient and physician
      alike. Making an accurate diagnosis is important to help the athlete return to
      effective training and maximal performance. Overtraining syndrome is a possible
      cause, but at this time remains a diagnosis of exclusion.

PMID- 15509472
TI  - Injections and return to play.
AB  - The use of analgesic and anti-inflammatory injections in athletics has a long and
      sometimes controversial history. They have been and will continue to be utilized
      to decrease inflammation and pain, improve healing time, and ultimately decrease
      the amount of time missed from sports competition. Several authors have evaluated
      both the positive and negative aspects of various injectable medicines. Many
      questions still remain with regard to safety, tolerability, risks, complications,
      and side effects of these injectable medicines. This paper reviews some of the
      current trends regarding the use of injectable medications in athletic medicine.

PMID- 15509473
TI  - Current concepts in concussion rehabilitation.
AB  - Active rehabilitation of sport injuries is a concept familiar to athletes and
      those caring for them. Rehabilitation goals aim to optimize recovery efficiency
      and diminish chances of repeat injury. Rehabilitation programs take many aspects
      of recovery and wellness into consideration including physical, social, and
      psychologic components. Ultimately, this is important in the recovery process
      after concussion. In this article we introduce the largely unexplored concept of
      multidimensional concussion rehabilitation and discuss physical, psychologic,
      social, and sport-specific issues. As well, we propose future directions in this
      field.

PMID- 15509474
TI  - Pregnancy as an opportunity for behavior change.

PMID- 15509475
TI  - Exercise prescription for the prevention of obesity in adolescents.
AB  - Childhood obesity is a major public health problem and poses important challenges
      for both health care and school-centered environments. Each faces difficulties in
      successfully addressing this problem: school personnel report lack of training in
      intervention, and health providers report ineffective office-based intervention
      strategies. With coordination of interventions in the school and office,
      prevention and treatment of childhood obesity can be improved. Toward this, the
      function of prescribing exercise as a preventive treatment can be very effective.
      This review evaluates recent literature upon the health care provider's role in
      and out of the medical office at prescribing exercise and the associated health
      benefits of exercise for children. Thus, health professionals caring for children
      and adolescents are in a key position to help prevent and treat obesity by
      promoting behavioral and environmental changes. Although the evidence base is
      insufficient to provide specific guidelines for assessment and treatment of all
      aspects of child and adolescent obesity, the following recommendations reflect
      critical reviews of the literature and are based upon expert committee
      guidelines.

PMID- 15509476
TI  - Prescribing exercise for the elderly: current research and recommendations.
AB  - The potential for regular exercise to offset the deleterious effects of aging is
      well established. In fact, the pronounced health benefits attributed to regular
      exercise, including improvements in resting blood pressure, cholesterol profile,
      osteoarthritis, osteoporosis, diabetes mellitus, and cognitive functioning, can
      be achieved even in those individuals who start physical conditioning programs
      later in life. Yet, despite these impressive data, approximately 70% of elderly
      Americans are physically inactive. This hypokinetic state negatively affects not
      only the health status of the elderly but significantly influences healthcare
      costs as more Americans are attaining octogenarian status. As such, it is vitally
      important for all healthcare workers to actively encourage elderly individuals to
      maintain or, in the case of nonexercisers, start an exercise program. Such
      recommendations may help to decrease comorbid conditions associated with the
      aging process, increase functional independence, and attenuate skyrocketing
      healthcare costs associated with treating the growing elderly population.

PMID- 15509477
TI  - Exercise prescription for underprivileged minorities.
AB  - Physical inactivity is a growing epidemic in industrialized nations, contributing
      to the increasing prevalence and worsening of many chronic disease processes such
      as diabetes mellitus, cerebral vascular disease, and depression. It is well
      recognized that certain subpopulations are less likely to partake in physical
      activity than the population at large. Many minority populations, especially
      those of lower socioeconomic status, and women and children within these groups,
      are the most likely to be inactive. Promotion of increased physical activity
      within these subpopulations has been fraught with many obstacles. Interventions
      need to be developed with these groups in mind, addressing the beliefs and
      barriers specific to each group. This article reviews the available research on
      physical activity within minority populations, the barriers that exist, and
      offers recommendations on methods to increase adoption and maintenance of
      physical activity within minority groups.

PMID- 15509478
TI  - Modern pathological evaluation of soft tissue sarcoma specimens and its potential
      role in soft tissue sarcoma research.
AB  - The vast majority of soft tissue tumors (STT), especially sarcomas, should be
      examined according to a national standard for pathologic evaluation, including a
      national consensus on a grading system and elements of a synoptic pathology
      report. The margins should be separated into fascial margins and other surgically
      cut margins. If questions about the diagnosis arise, a second opinion should be
      sought from an expert in sarcoma pathology. Whenever possible, tissue should be
      frozen for potential molecular diagnosis and additional tissue banked for
      research. Finally, there is a need for a national registry for rare sarcoma
      types.

PMID- 15509479
TI  - Primary multidisciplinary management of extremity soft tissue sarcomas.
AB  - Soft tissue sarcomas (STS) are a rare and heterogeneous group of malignancies
      that most commonly present as large painless masses deep in the muscular
      compartments of the extremities. Investigation and treatment of these patients
      must be undertaken at a tertiary referral unit. Staging studies must include a
      high-quality magnetic resonance imaging (MRI) scan of the local site and a
      computed tomography (CT) scan of the chest to investigate for possible metastatic
      disease. Review of biopsy material must be undertaken by an experienced
      musculoskeletal pathologist. Currently, histologic diagnosis and grade are
      assigned to the tumor, but in tumors such as synovial sarcoma and Ewing's family
      of tumors, molecular evaluation is becoming crucial for diagnostic, prognostic,
      and therapeutic reasons. Surgical resection of sarcomas with negative surgical
      margins remains the mainstay of treatment. Surgical treatment alone is indicated
      for small superficial masses that are not adjacent to bone or neurovascular
      structures. However, in large deep masses where surgical margins are likely to be
      close in order to preserve important neurovascular structures and bone, combined
      treatment using surgical resection and radiation results in acceptable local
      control rates and reasonable patient function. It is incumbent on the management
      team to decide on timing of radiotherapy as a practice. This decision is based on
      several factors but potential complications must be taken into account. In this
      regard the long-term effects on normal tissues must be considered. Functional
      outcome has become an essential consideration when recommending treatment. If
      promising techniques become available to reduce the incidence of wound
      complications or to decrease the dose of radiation to normal tissue, preoperative
      radiation should be considered in light of its lower incidence of long-term
      effects that result in reduction in patient function.

PMID- 15509480
TI  - Optimizing radiation therapy and post-treatment function in the management of
      extremity soft tissue sarcoma.
AB  - When treating soft tissue sarcomas (STS) of the extremities, the major
      therapeutic goals are survival, local tumor control, optimal function, and
      minimal morbidity. Surgical resection of the primary tumor is the essential
      component of treatment for virtually all patients. However, local control by
      surgery alone is poor for the majority of patients with extremity lesions unless
      the procedure removes large volumes of grossly normal tissue (ie, widely negative
      margins are attained, because sarcomas tend to infiltrate normal tissue adjacent
      to the evident lesion). Thus, removal of the gross lesion by a simple excision
      alone is followed by local recurrence in 60% to 90% of patients. Radical
      resections reduce the local recurrence rate to 10% to 30%, but may compromise
      limb function. The combination of function-sparing surgery and radiation achieves
      better outcomes than either treatment alone for nearly all patients with STS.
      Because both surgical and radiation technique are critically important for
      optimizing local control of tumor and functional outcome, it is important to
      manage these patients in dedicated multispecialty clinics comprised of physicians
      with expertise in sarcomas, including orthopedic and general oncologic surgeons,
      radiation oncologists, medical oncologists, sarcoma pathologists, and bone and
      soft tissue diagnostic radiologists. Radiation therapy can be given by external
      beam radiation therapy (EBRT) or brachytherapy (BRT) or combination thereof.
      External beam radiation can be given either preoperatively or postoperatively.
      The clinical considerations and the outcome data that must be considered in
      choosing the most appropriate treatment technique for the individual patient are
      discussed.

PMID- 15509481
TI  - Rehabilitation and quality-of-life issues in patients with extremity soft tissue
      sarcoma.
AB  - The current standard of care for soft tissue sarcoma (STS) is limb salvage
      surgery and adjuvant radiotherapy, with long-term survival rates of approximately
      70%. However, the extensive surgical resection and subsequent reconstruction
      result in 50% of survivors living with chronic disability. Rehabilitation aims to
      optimize functional independence and quality of life, and is routinely offered to
      patients undergoing surgical treatment for STS. Unfortunately, there is a dearth
      of research related to rehabilitation in this area. We propose a model for
      assessing disability, for designing treatment interventions and for evaluating
      rehabilitative outcomes in STS. The World Health Organization's (WHO)
      international classification of functioning, disability, and health (ICF) is
      divided into three domains: 1) impairments (related to body structure and
      function), 2) activity limitations (related to usual self-care
      activities/activities of daily living), and 3) participation restrictions
      (related to social roles). A literature review of STS rehabilitation reveals that
      most studies have focused on disability assessment, with few papers describing or
      evaluating rehabilitation interventions commonly employed in STS. Clinicians are
      forced to extrapolate findings from other patient populations in order to
      evaluate the effectiveness of specific rehabilitation strategies (ie, those used
      for particular sequelae of STS, such as lymphedema or impaired exercise
      tolerance). There is strongest support for complex decongestive physiotherapy
      (targeting lymphedema) and aerobic exercise interventions (aimed at alleviating
      cancer-related fatigue and psychosocial sequelae). The most poorly researched
      topic is rehabilitation for genitourinary disability (both incontinence and
      sexual dysfunction). Most studies related to oncologic rehabilitation are
      restricted to the impairment level (eg, affecting range of motion, muscle
      strength) of the ICF, with only a small minority addressing activity limitations
      (eg, affecting activities of daily living) experienced by patients. A
      consideration of participation restrictions (eg, fulfillment of vocational roles)
      is almost wholly absent from the literature. Yet social role reintegration is of
      fundamental importance to patients. Further research is required in these two
      domains. The ICF provides a comprehensive framework for future research into
      rehabilitation interventions for STS.

PMID- 15509482
TI  - Therapeutic strategies for local recurrent malignant glioma.
AB  - Patients with local recurrent malignant gliomas present diagnostic and
      therapeutic challenges for the neuro-oncology practitioner. Management must be
      individualized depending on the patient's age, performance status, histology,
      response to initial therapy, type of recurrence (local vs diffuse), and time
      since original diagnosis. Treatment options may be classified into surgery,
      additional radiation therapy, or chemotherapy. Results of treatment are often
      difficult to determine because of limitations of conventional imaging. Symptom
      palliation is an important goal that often requires additional adjuvant medical
      therapy. Quality of life issues are also of paramount importance in patients with
      recurrent malignant glioma and frequently will guide management strategy.
      Finally, patients with recurrent malignant gliomas should be encouraged to
      consider participation in a clinical trial in the hopes that better treatment
      alternatives will be available for this group of patients within the next few
      years.

PMID- 15509483
TI  - Meningioma: current treatment options and future directions.
AB  - Benign meningiomas can be observed if not symptomatic or growing. When treatment
      is indicated, the options are surgery, radiosurgery, fractionated radiation
      therapy, or a combination of these modalities. Except in certain cases, such as
      large tumors that require debulking for relief of symptoms, we do not recommend
      the routine use of combination therapy. Intracranial meningiomas have usually
      been treated with surgical resection with an expected durable local control of
      80% to 90% when a gross total resection (GTR) is obtained. Patients who have
      inoperable disease, refuse surgery, undergo less than a GTR, or who have
      aggressive histology should instead be considered candidates for radiation
      therapy or radiosurgery. While benign meningiomas can be successfully treated
      definitively or postoperatively with either fractionated radiation therapy or
      single fraction radiosurgery, atypical or malignant lesions are best treated with
      fractionated radiation therapy with conventional dosimetric margins. The role of
      systemic therapy is not yet defined, but multiple agents are being investigated
      in early phase trials for patients with recurrent or progressive disease after
      standard therapy has failed.

PMID- 15509484
TI  - The management of thromboembolic disease in patients with central nervous system
      malignancies.
AB  - Venous thromboembolic disease (VTE) is a common complication of malignancies
      affecting the central nervous system (CNS), both in the perioperative period and
      throughout the disease course. Until recently, the perceived risk of intracranial
      hemorrhage in patients with CNS malignancies was felt to be a relative
      contraindication to systemic anticoagulation, and most patients were managed with
      nonpharmacologic methods in both the prophylactic and treatment setting. However,
      several studies of the safety and efficacy of anticoagulation in both
      neurosurgical and cancer patients have challenged the previous dogma, and routine
      use of unfractionated heparin or low molecular weight heparin (LMWH) for VTE
      prophylaxis in patients undergoing craniotomy for CNS malignancy is recommended.
      Likewise, treatment of established VTE in this population with heparins is
      recommended, at least initially, followed by long-term treatment either with
      heparin or oral warfarin. Complications of inferior vena cava (IVC) filters, used
      as an alternative to systemic anticoagulation, appear to be more common in brain
      tumor patients with VTE, lending further support to treatment with systemic
      anticoagulation when possible. We advocate a multimodality approach utilizing
      compression stockings, intermittent compression devices, and heparin in the
      perioperative setting as the best proven method to reduce the risk of VTE. In the
      absence of a strict contraindication to systemic anticoagulation, such as
      previous intracranial hemorrhage or profound thrombocytopenia, LMWH is
      recommended in brain tumor patients with newly diagnosed VTE, followed by long
      term warfarin or LMWH.

PMID- 15509485
TI  - Targeted molecular therapy for malignant gliomas.
AB  - Advances in our understanding of the molecular changes and resultant cellular
      effects in malignant glioma are expanding the opportunities for novel targeted
      therapies. At present, chemotherapy and radiation followed by chemotherapy with
      nonselective cytotoxic agents is emerging as a standard treatment option for
      patients with malignant glioma. Unfortunately significant improvements in
      response and survival have not occurred for the majority of patients. The
      continued improvement in patient outcomes will require the incorporation of
      glioma-specific therapies either in the form of compounds specifically targeted
      to glioma-specific receptors or that inhibit signaling pathways promoting glioma
      survival and progression.

PMID- 15509486
TI  - Recommendations for studies on detection of neck disease.

PMID- 15509487
TI  - Cytotoxic drugs, radiotherapy and oral candidiasis.
AB  - The increased incidence of oral candidiasis in patients with malignancies stems
      partly from the systemic disease itself and, partly from the therapeutic measures
      such as cytotoxic and other immunosuppressive drugs and radiotherapy they receive
      during management of such malignancies. In this review we discuss the clinical
      and laboratory findings on the relationship between cytotoxics, radiotherapy and
      oral candidiasis, possible mechanisms of pathogenicity following such therapy, as
      well as precautions that could be taken to minimize such recalcitrant yeast
      infections.

PMID- 15509488
TI  - Complications of free flap transfers for head and neck reconstruction following
      cancer resection.
AB  - The reported success rate of microvascular free flap reconstruction ranges
      between 95% and 97%. However when complications occur, they must be identified
      early and managed efficiently because there is a narrow window of opportunity to
      salvage potential flap failure. While technical advances in instrumentation and
      magnification have improved overall success rates, the rare complication may
      prove devastating for the patient, his/her hospital stay, and the optimum
      rehabilitation. Complications of microvascular free tissue transfer may occur at
      the recipient site or at the donor site. Complications occurring at the recipient
      site are largely a result of vessel thrombosis while complications occurring at
      the donor site may result from many causes, ranging from infection to those
      related to the harvesting of the flap. Irrespective of the site of the
      complication, it is essential that complications be recognized and addressed
      early in their course to prevent or minimize devastating consequences.

PMID- 15509489
TI  - The correlation between epithelial cell proliferation and inflammation in
      odontogenic keratocyst.
AB  - The objective of this study was to investigate the effect of inflammation on Ki
      67 and PCNA labeling indices of odontogenic keratocysts. The study included 45
      cases of OKC. From each case, three 5-microm sections were cut and stained with
      hematoxylin and eosin and with monoclonal antibodies for PCNA and Ki-67. In 10
      high power fields (HPF), the type of epithelial lining was recorded separately
      for each field (metaplastic squamous or classic parakeratinized). Labeling
      indices for Ki-67 and PCNA and the inflammatory infiltrate density in the depth
      of 1 HPF adjacent to the basement membrane were recorded for each HPF. Parameters
      were compared between fields, and for each case the average inflammatory score
      and average labeling indices were calculated, and cases compared. No inflammation
      was observed in 24.5% of cases, mild in 30.5% and moderate to severe in 45%. Foci
      of metaplastic non-keratinizing epithelium were observed in 64% of cases, which
      were twice as common in inflamed cysts (90%) than in non-inflamed cysts (44%).
      The average labeling indices for PCNA and Ki-67 yielded no significant
      differences between inflamed and non-inflamed cysts. When compared between HPF's,
      there was an increase in the Ki-67 labeling index in metaplastic epithelium in
      areas with moderate to severe inflammation score (p=0.036). PCNA labeling index
      did not significantly change between areas with low and high inflammation. No
      differences in labeling indices were observed between areas of classic and
      metaplastic epithelium with equal inflammation density. A focal increase in Ki-67
      expression adjacent to moderate to severe inflammation was found, with no
      significant effect on the overall proliferation activity of the cysts.

PMID- 15509490
TI  - Lip cancer experience in Mexico. An 11-year retrospective study.
AB  - Lip cancer is the most frequent malignant neoplasm of the oral cavity; however,
      there is no information available on the incidence of this type of cancer in
      Mexico. This study provides information about the clinico-pathological features
      of lip cancer patients admitted at a cancer hospital in Mexico City during an 11
      year period and describes the treatment modalities performed and their results. A
      total of 113 patients were studied. There were 74 men (65.5%) and 39 women
      (34.5%), ranging in age from 14 to 106 years (mean 70 years). In 53 cases (46.9%)
      an association was found between the disease and chronic sun exposure.
      Additionally, positive smoking antecedents were recorded in 58 cases (51.3%). As
      15 patients were followed for less than 1 month, they were excluded for further
      analysis. There were 82 cases (83.7%) of squamous cell carcinoma, 10 (10.2%)
      basal cell carcinomas, and one case (1%) each of adenocarcinoma NOS, melanoma,
      adenoid cystic carcinoma, Merkel cell carcinoma, lymphoepithelioma and
      angiosarcoma. We observed an incidence of malignant neoplasms in the upper lip of
      33.7%, which is higher than most of the published series and may be due to the
      fact that in this series we included all histological types of lip cancers. Fifty
      percent of the cases were found in stages III and IV. Cervical lymph node
      metastases were found in 21% of patients with no previous treatment, and they
      developed in 5.3% after treatment. Our data suggest that tumoral size is directly
      related to the possibility of developing node metastases, as none of them
      occurred in patients T1, whereas 10 (62.5%) of the patients in T4 presented them.
      Seven deaths were documented (7.1%), five of which corresponded to squamous cell
      carcinoma, one to Merkel cell carcinoma, and one to adenocarcinoma. Deaths were
      directly related to the disease in six cases, and one patient died due to
      surgical complications. Distant metastases were found in only two patients, one
      of which coursed with an adenocarcinoma and the other with a Merkel cell
      carcinoma. Based on the present results, we suggest that the differences
      encountered with respect to other series, particularly the higher incidence found
      in women, the frequent presentation of this type of neoplasms in the upper lip,
      the wide variety of histopathological diagnoses and the high frequency of cases
      with cervical lymph node affection, should lead us to search for multi-modal
      treatment alternatives in this population.

PMID- 15509492
TI  - Effectiveness of radiochemotherapy on lymph node metastases in patients with
      stage IV oropharyngeal cancer.
AB  - Radiochemotherapy plays a leading role in the treatment of patients with advanced
      squamous cell carcinomas (SCC) of the oropharynx. The aim of the present study
      was to estimate its effectiveness on lymph node (LN) metastases. Seventeen
      patients with advanced UICC stage IV oropharyngeal SCC (1xT2, 4xT3, 12xT4, 2xN1,
      15xN2) were observed prospectively. They were treated with radiochemotherapy
      (total radiation doses 60-70.6 Gy). One to four months after neck dissection (ND)
      was performed. Specimens were histologically examined for metastases according to
      the neck levels obtained from. Local control was achieved in 14/17 (82.4%)
      patients and regional-in 10/17 (58.8%) patients. Of 566 LN studied, 29 exhibited
      signs of involvement. Two from 29 were found in neck level I, 20/29 in II, 6/29
      in III and 1/29 in IV. In 13/29 LN the metastases had completely regressed under
      treatment whereas 16/29 LN (7 patients) contained vital tumoral tissue. The
      observed high incidence of vital LN metastases, which abide the
      radiochemotherapy, advocates further studies, concerning the value of planed ND
      after radiochemotherapy.

PMID- 15509491
TI  - Multicenter phase I trial of induction chemotherapy with docetaxel and nedaplatin
      for oral squamous cell carcinoma.
AB  - A phase I study of combination neoadjuvant chemotherapy with docetaxel (DOC) and
      nadaplatin (CDGP) was conducted in patients with untreated, advanced but operable
      oral squamous cell carcinoma. DOC was administered (one-hour i.v. infusion) on
      day 1 followed by CDGP (one-hour i.v. infusion). The dose levels of DOC and CDGP
      tested were 60/70, 60/80, 60/90, 60/100, and 70/100 (mg/m(2)). Fifteen patients
      enrolled in this study and median age was 60 years. Dose-limiting toxicity (DLT)
      occurred in one of six patients at DOC dose of 60 mg/m(2) and CDGP dose of 100
      mg/m(2). The DLT was diarrhea. Because one additional patient at this dose-level
      developed grade 4 neutropenia lasting for 4 days that approached DLT and because
      fear of severe hematological problems was predicted, further dose escalation was
      not performed. This combination chemotherapy is active and well tolerated and
      warrants a phase II study. We recommended 60 mg/m(2) DOC and 100 mg/m(2) CDGP for
      phase II study.

PMID- 15509493
TI  - Embryological study of the glottic site and clinical implications.
AB  - The development of the glottic site, in particular of its ventral area, was
      studied to better understand the spreading pathways of T1, T2 cancer. Serial
      sections of larynges from human embryos, fetuses and adults were observed. A
      dorsal, a ventral and an intermediate compartment were found on the basis of
      their maturation schedule. A commissure muscle which develops in the anterior one
      third of the glottic site and wraps the connection system of vocal ligaments was
      recognized. The inferior paraglottic space, the compartment structures and the
      localization of superficial and deep blood vessels and of glands in the ventral
      compartment and the components of Broyles ligament were studied during
      ontogenesis. The compartments identified here have clinical and oncological
      relevance. Their detailed knowledge offers a prerequisite for planning and
      performing compartment conservative surgery in T1, T2 cancer, based on their
      spreading pathways.

PMID- 15509494
TI  - Detection of plasminogen activators in oral cancer by laser capture
      microdissection combined with zymography.
AB  - Plasminogen activation is believed to be critical to the progression of oral
      squamous cell carcinoma by facilitating matrix degradation during invasion and
      metastasis, and high levels of urokinase plasminogen activator (uPA) and
      plasminogen activator (PA) inhibitor-1 (PAI-1) in tumors predict poor disease
      outcome. We describe the development of a novel method for studying PA in oral
      cancer that combines the sensitivity and specificity of zymography with the
      spatial resolution of immunohistochemistry. Laser capture microdissection (LCM)
      was combined with plasminogen-casein zymography to analyze uPA, tissue PA (tPA),
      uPA-PAI-1 complexes, and tPA-PAI-1 complexes in 11 tumors and adjacent non
      malignant epithelium from squamous cell carcinomas of the tongue, floor of mouth,
      larynx, and vocal cord. uPA was detectable in all tumor samples analyzed, uPA-PAI
      1 complexes in three samples, and tPA in nine. PA was detectable in as little as
      0.5 microg protein lysate from microdissected tumors. In all specimens, uPA
      expression was highly increased in tumor tissue compared to adjacent non
      malignant tissue. In conclusion, LCM combined with zymography may be excellently
      suited for analyzing the prognostic significance and causal involvement of the
      plasminogen activation system in oral cancer.

PMID- 15509495
TI  - Genome wide instability scanning in chewing-tobacco associated oral cancer using
      inter simple sequence repeat PCR.
AB  - Genomic instability plays a major role in cancer, facilitating tumour progression
      and tumour heterogeneity. Inter simple sequence repeat PCR (ISSR-PCR) is a
      sensitive tool for detection of whole genome scanning. In fifteen oral cancer
      patients, using tumor tissue and adjacent normal tissue DNA, we investigated
      genomic instability regions using ISSR-PCR assay. The genomic fragments were
      cloned, sequenced and identified. Two-anchored dinucleotide repeat primers,
      (CA)(8)A/GG and (CA)(8)A/GC/T, were used in the study. About 40-50 fragments were
      observed on polyacrylamide gel electrophoresis, with 25 distinct fragments of
      less than 2 kb. The electrophoretic pattern highlighted several distinct
      fragments in tumor adjacent normal tissues. The distinct fragments of 258, 325,
      430, 440, 600 and 900 bp sizes using (CA)(8)A/GG primer, and 300, 475, 675 and
      800 bp using (CA)(8)A/GC/T primers, in the normal tissues showed partial (>50%)
      or complete loss in multiple tumor tissues. These fragments were eluted from the
      gel, cloned in pMos Blue vector and subjected to nucleotide sequencing. Insilico
      analysis defined the specific genomic sequences, given as follows: RP11-399D2 ()
      on chromosome (chr)4; RP1-39J2 (), NKp44RG () and RP11-518I13 () on chr6; NC-T-2
      () on chr7; RP11-586K2 () and RP11-495O10 () on chr8; RP11-101K10 () on chr9; R
      794A8 () on chr14; and RP11-679B19 () on chr16. The sequences of our clones have
      been submitted to NCBI gene bank, accession numbers to , and . The Genomic
      Instability Index was calculated and ranged from 6% to 28.5% (median 12%) in the
      oral cancer samples, excluding one case where genomic instability was not
      observed. Thus, our results indicate presence of widespread genomic alterations
      in chewing-tobacco associated oral cancers.

PMID- 15509496
TI  - Differential expression of the non-receptor tyrosine kinase BRK in oral squamous
      cell carcinoma and normal oral epithelium.
AB  - BRK is a non-receptor tyrosine kinase whose functional role is poorly understood.
      Although it is an epithelial specific kinase, its expression appears to be tissue
      specific. To date, little is known about BRK expression in human oral epithelium.
      We investigated expression of BRK in human oral squamous cell carcinomas (OSCC)
      and normal oral epithelium (NOE) using immunohistochemistry, laser confocal
      microscopy and Western blotting. The subcellular localization of BRK was
      identified by confocal microscopy and Western blotting of nuclear and cytoplasmic
      extracts from these cells. The results indicate that NOE express higher levels of
      BRK compared with OSCC cells. In NOE and moderately differentiated OSCC cells,
      BRK was localized in the nucleus and cytoplasm. However, in poorly differentiated
      OSCC cells, BRK was localized in perinuclear regions. These results suggest that
      BRK expression differs in normal and OSCC which may reflect a possible functional
      involvement in OSCC.

PMID- 15509497
TI  - NF-kappaB involvement in tumor-stroma interaction of squamous cell carcinoma.
AB  - We investigated the interaction between tumor cells and stromal fibroblasts in
      tumor invasion of oral squamous cell carcinoma. Gelatin zymography showed that
      high levels of matrix metalloproteinase (MMP)-9 were present in the tissue of
      squamous cell carcinoma. When tumor cells and fibroblasts were isolated from the
      tissue and cultured separately, significant levels of MMP-9 were lost in the
      culture media of tumor cells as well as fibroblasts. When tumor cells and
      fibroblasts were cocultured in the presence of tumor necrosis factor alpha, high
      levels of MMP-9 were recovered in the culture media. The levels of MMP-9, which
      were secreted from tumor cells, but not fibroblasts, correlated with the number
      of cocultured fibroblasts. Cocultured fibroblasts, moreover, enhanced the
      induction of an active form of MMP-9, cell motility, and the activation of a
      transcription factor NF-kappaB in tumor cells. Stromal fibroblasts may induce NF
      kappaB activation and promote the invasion of oral squamous cell carcinoma.

PMID- 15509498
TI  - Oral lichenoid lesions: what are they?

PMID- 15509500
TI  - AAV vector-mediated microdystrophin expression in a relatively small percentage
      of mdx myofibers improved the mdx phenotype.
AB  - Duchenne muscular dystrophy (DMD) is a lethal disorder of skeletal muscle caused
      by mutations in the dystrophin gene. Adeno-associated virus (AAV) vector-mediated
      gene therapy is a promising approach to the disease. Although a rod-truncated
      microdystrophin gene has been proven to ameliorate dystrophic phenotypes, the
      level of microdystrophin expression required for effective gene therapy by an AAV
      vector has not been determined yet. Here, we constructed a recombinant AAV type 2
      vector, AAV2-MCKDeltaCS1, expressing microdystrophin (DeltaCS1) under the control
      of a muscle-specific MCK promoter and injected it into TA muscles of 10-day-old
      and 5-week-old mdx mice. AAV2-MCKDeltaCS1-mediated gene transfer into 5-week-old
      mdx muscle resulted in extensive and long-term expression of microdystrophin and
      significantly improved force generation. Interestingly, 10-day-old injected
      muscle expressed microdystrophin in a limited number of myofibers but showed
      hypertrophy of microdystrophin-positive muscle fibers and considerable recovery
      of contractile force. Thus, we concluded that AAV2-MCKDeltaCS1 could be a
      powerful tool for gene therapy of DMD.

PMID- 15509501
TI  - Targeted expression of insulin-like growth factor-I reduces early myofiber
      necrosis in dystrophic mdx mice.
AB  - Necrosis of dystrophic myofibers in Duchenne muscular dystrophy and mdx mice
      results from defects in the subsarcolemmal protein dystrophin that cause membrane
      fragility and tears in the sarcolemma, and these lead to the destruction of the
      myofibers. The present study specifically tests whether overexpression of mIGF-1
      in mdx/mIGF-1 transgenic mice reduces myofiber breakdown during the acute onset
      phase of dystrophy (at 21 days). The extent of muscle damage and Evans blue dye
      (EBD) staining of myofibers was quantitated histologically for mdx/mIGF-1 and
      their mdx littermates from 15 to 30 days of age. Overexpression of mIGF-1
      strikingly reduced the extent of myofiber damage (histology and EBD staining) by
      up to 97% in tibialis anterior and quadriceps muscles at 21-22 days after birth.
      In the mdx diaphragm, the onset of muscle breakdown was earlier (by 15 days after
      birth) but no significant protective effect of IGF-1 was apparent within the
      first month of age in mdx/IGF-1 mice. These novel observations show that
      increased mIGF-1 within mdx myofibers specifically reduces the breakdown of
      dystrophic muscle during the acute onset of muscle degeneration. This mechanism
      of action can account for the long-term reduced severity of the dystropathology
      in mdx mice that overexpress mIGF-1 and provides promising opportunities for
      therapeutic strategies.

PMID- 15509502
TI  - Vascular endothelial growth factor stimulates skeletal muscle regeneration in
      vivo.
AB  - Vascular endothelial growth factor (VEGF) is a major regulator of blood vessel
      formation during development and in the adult organism. Recent evidence indicates
      that this factor also plays an important role in sustaining the proliferation and
      differentiation of different cell types, including progenitor cells of different
      tissues, including bone marrow, bone, and the central nervous system. Here we
      show that the delivery of the 165-aa isoform of VEGF-A cDNA using an adeno
      associated virus (AAV) vector exerts a powerful effect on skeletal muscle
      regeneration in vivo. Following ischemia-, glycerol-, or cardiotoxin-induced
      damage in mouse skeletal muscle, the delivery of AAV-VEGF markedly improved
      muscle fiber reconstitution with a dose-dependent effect. The expression of both
      VEGF receptor-1 (VEGFR-1) and VEGFR-2 was upregulated both in the satellite cells
      of the damaged muscles and during myotube formation in vitro; the VEGF effect was
      mediated by the VEGFR-2, since the transfer of PlGF, a VEGF family member
      interacting with the VEGFR-1, was ineffective. These results are consistent with
      the observation that VEGF promotes the growth of myogenic fibers and protects the
      myogenic cells from apoptosis in vitro and prompt a therapeutic use for VEGF gene
      transfer in a variety of muscular disorders.

PMID- 15509503
TI  - Systemic but not intraocular Epo gene transfer protects the retina from light-and
      genetic-induced degeneration.
AB  - Molecules with neurotrophic activity are being evaluated for treatment of
      retinitis pigmentosa in animal models. In particular, great interest has been
      focused recently on erythropoietin (Epo). Evidence of its neurotrophic activity
      comes mainly from data demonstrating photoreceptor protection in a rodent light
      damage model through systemic administration of a recombinant form of this
      hormone. Our goal was to test whether Epo retinal gene transfer can rescue or
      delay photoreceptor cell death. We delivered adeno-associated viral vectors
      encoding Epo intraocularly and, for comparison, intramuscularly to one light
      induced and two genetic models of retinal degeneration. Intraocular Epo gene
      transfer resulted in sustained hormone expression in the eye, which was
      undetectable systemically. In contrast, Epo intramuscular gene transfer resulted
      in hormone secretion in the circulation, which was not detected in ocular fluids.
      The protein secreted from muscle and retina is of the same molecular weight as a
      commercial recombinant human Epo. Interestingly, following systemic but not
      intraocular Epo delivery, morphological photoreceptor protection was observed in
      the light-damage and rds/peripherin (Prph2) models of retinal degeneration. In
      the light-damage model, the morphological rescue was accompanied by a significant
      electrophysiological improvement of photoreceptor function. In contrast, no
      photoreceptor rescue was observed following Epo gene transfer in the rd10 model.
      This suggests that different apoptotic mechanisms, with varying sensitivities to
      Epo, occur in different retinal degeneration models. In conclusion, our data
      support Epo as a neuroprotective agent in some, but not all, retinal
      degenerations. Further, rescue is observed in specific models after systemic but
      not intraocular Epo gene transfer.

PMID- 15509504
TI  - Enhanced in vivo selection of bone marrow cells by retroviral-mediated
      coexpression of mutant O6-methylguanine-DNA-methyltransferase and HOXB4.
AB  - To attain therapeutic levels of gene-modified hematopoietic stem cells, it may be
      necessary in the majority of disorders to provide an in vivo selective advantage
      that facilitates the expansion of their numbers. A popular strategy to achieve in
      vivo selection has been to employ drug selection while coexpressing a transgene
      that conveys chemoresistance, such as O6-methylguanine-DNA-methyltransferase
      (MGMT). An alternate approach is to confer an enhanced proliferative potential
      upon gene-modified hematopoietic stem cells through the delivery of the homeobox
      transcription factor HOXB4. By developing a novel tricistronic retroviral vector,
      we have facilitated the simultaneous coexpression of a mutant version of MGMT and
      HOXB4 in retrovirally transduced bone marrow. Using an in vivo competitive
      repopulation assay, we demonstrate that primary bone marrow cells containing this
      construct show enhanced reconstitution following transplant and improved
      selection subsequent to chemotherapeutic challenge in comparison to cells
      expressing either HOXB4 or MGMT alone. This selection advantage was evident even
      when HOXB4/MGMT-coexpressing cells were infused along with a large excess of
      unmodified cells. We propose that this selection cassette may facilitate the in
      vivo expansion of gene-modified hematopoietic stem cells at a level in excess of
      previous strategies.

PMID- 15509505
TI  - Insertion of retroviral vectors in NOD/SCID repopulating human peripheral blood
      progenitor cells occurs preferentially in the vicinity of transcription start
      regions and in introns.
AB  - Reports on insertional "genotoxicity" in patients have created intense interest
      in characterizing retroviral vector integrations on the genomic level. The
      retroviral vector SF91m3 was used for transduction of human peripheral blood
      progenitor cells (PBPC). These PBPC were transplanted into nonobese
      diabetic/severe combined immunodeficient mice. A total of 186 retroviral vector
      integration sites were isolated by ligation-mediated PCR from chimeric mouse bone
      marrow of five PBPC donors, sequenced, and blasted against the human genome.
      Preferred integration near the transcription start regions, within CpG islands,
      and within Alu regions was observed. Detailed analysis of targeted RefSeq genes
      showed a favored integration within the first intron. Integrations were most
      common in genes coding for signaling proteins, transcription factors, and
      kinases. In all genes targeted independently multiple times the respective
      orientation of the provirus within the gene was identical, indicating integration
      hot spot regions and similar steric determinants for integration sites. Possible
      explanations for these findings could be nonrandom vector integration, clonal
      selection due to gene expression interference, or engraftment issues related to
      gene insertion in signaling and cell cycle genes. The low frequency of
      integrations in exons may be reassuring as to the safety of retroviral gene
      therapy with normal human PBPC.

PMID- 15509506
TI  - Competitive repopulation assay of two gene-marked cord blood units in
      NOD/SCID/gammac(null) mice.
AB  - In multiunit cord blood transplantation, hematopoietic stem cells from each
      unrelated cord blood (UCB) unit competitively reconstitute the hematopoietic
      system in a recipient. To evaluate the fate of the progeny of each UCB unit and
      to determine the effects of graft-versus-graft reaction, we established a novel
      competitive repopulation assay using NOD/SCID/gammac(null) mice in which human T
      lymphocytes develop from CD34+ cells. CD34+ cells from each UCB unit were labeled
      with recombinant lentivirus vectors carrying genes encoding either enhanced green
      fluorescent protein (EGFP) or enhanced yellow fluorescent protein (EYFP).
      Hematopoietic chimerism composed of both EGFP+ and EYFP+ cells was stably
      maintained up to 6 months after transplantation with purified CD34+ cells; the
      ratio of EGFP+ to EYFP+ cells in peripheral blood and bone marrow
      posttransplantation was equivalent to the ratio of these cells at
      transplantation. However, when mononuclear cells from two UCB units were
      cotransplanted with CD34+ cells, engraftment was highly competitive, with cells
      from only one or the other of the two UCB units surviving. Further
      subfractionations of mononuclear cells indicate that the skewed chimerism that is
      often observed in clinical multiunit cord blood transplantation may be mediated
      by the cooperation of both CD4+ and CD8+ T cells. The assay established here will
      be a useful tool for analyzing hematopoietic reconstitution in clinical multiunit
      cord blood transplantation.

PMID- 15509507
TI  - Sustained phenotypic correction of hemophilia a mice following oncoretroviral
      mediated expression of a bioengineered human factor VIII gene in long-term
      hematopoietic repopulating cells.
AB  - Hematopoietic stem cells (HSCs) are an attractive target cell population for
      hemophilia A gene therapy because of their capacity to regenerate the
      hematolymphoid system permanently following transplantation. Here we transplanted
      bone marrow (BM) cells transduced with a splicing-optimized MSCV oncoretroviral
      vector expressing a secretion-improved human factor VIII gene into
      immunocompromised hemophilic mice that had received a reduced dose conditioning
      regimen. An enhanced green fluorescent protein (EGFP) reporter gene linked to an
      encephalomyocarditis virus internal ribosome entry site was incorporated into the
      vector to allow preselection of transduced cells and facile evaluation of
      engraftment. Sustained expression of EGFP was demonstrated in the peripheral
      blood, and therapeutic levels of factor VIII were detected in the plasma of the
      majority of the recipients for the duration of the observation period (up to 22
      weeks). Coordinate expression of factor VIII and EGFP (up to 19 weeks) was
      transferred to secondary BM transplant recipients, indicating that long-term
      repopulating HSCs had been successfully gene modified. Notably, the hemophilic
      phenotype of all treated mice was corrected, thus demonstrating the potential of
      HSC-directed oncoretroviral-mediated factor VIII gene transfer as a curative
      therapeutic strategy for hemophilia A.

PMID- 15509508
TI  - Lentiviral vector-mediated gene transfer in T cells from Wiskott-Aldrich syndrome
      patients leads to functional correction.
AB  - Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency with a
      median survival below the age of 20 due to infections, severe hemorrhage, and
      lymphomas. Transplantation of hematopoietic stem cells from HLA-identical sibling
      donors is a resolutive treatment, but is available for a minority of patients.
      Transplantation of genetically corrected autologous hematopoietic stem cells or T
      cells could represent an alternative treatment applicable to all patients. We
      investigated whether WAS gene transfer with MMLV-based oncoretroviral and HIV
      based lentiviral vectors could restore normal functions of patients' T cells. T
      cells transduced either with lentiviral vectors expressing the WAS protein (WASP)
      from the ubiquitous PGK promoter or the tissue-specific WASP promoter or with an
      oncoretroviral vector expressing WASP from the LTR, reached normal levels of WASP
      with correction of functional defects, including proliferation, IL-2 production,
      and lipid raft upregulation. Lentiviral vectors transduced T cells from WAS
      patients at higher rates, compared to oncoretroviral vectors, and efficiently
      transduced both activated and naive WAS T cells. Furthermore, a selective growth
      advantage of T cells corrected with the lentiviral vectors was demonstrated. The
      observation that lentiviral vector-mediated gene transfer results in correction
      of T cell defects in vitro supports their application for gene therapy in WAS
      patients.

PMID- 15509509
TI  - The use of 19F spectroscopy and diffusion-weighted MRI to evaluate differences in
      gene-dependent enzyme prodrug therapies.
AB  - To evaluate noninvasive measures of gene expression and tumor response in a gene
      dependent enzyme prodrug therapy (GDEPT), a bifunctional fusion gene between
      Saccharomyces cerevisiae cytosine deaminase (CD) and Haemophilus influenzae
      uracil phosphoribosyltransferase (UPRT) was constructed. CD deaminates 5
      fluorocytosine (5FC) to 5-fluorouracil (5FU), and UPRT subsequently converts 5FU
      to fluorouridine monophosphate, and both of these reactions can be monitored
      noninvasively in vitro and in vivo using 19F magnetic resonance spectroscopy
      (MRS). Following transient transfection the CD-UPRT fusion protein exhibited both
      UPRT and CD enzymatic activities as documented by 19F MRS. In addition, an
      increase in CD activity and thermal stability was witnessed for the fusion
      protein compared to native CD. Stable expression of CD-UPRT in 9L glioma cells
      increased both 5FC and 5FU sensitivity in vitro compared to CD-expressing and
      wild-type 9L cells. Noninvasive 19F MRS of both CD and UPRT gene function in vivo
      demonstrated that in animals bearing CD-expressing tumors there was limited
      conversion of 5FC to 5FU with no measurable accumulation of cytotoxic fluorinated
      nucleotides (F-nucs). In contrast, CD-UPRT-expressing tumors had increased CD
      gene activity with a threefold higher intratumoral accumulation of 5FU and
      significant generation of F-nucs. Finally, CD-UPRT yielded increased efficacy in
      an orthotopic animal model of high-grade glioma. More importantly, early changes
      in cellular water mobility, which are felt to reflect cellular death, as measured
      by diffusion-weighted MRI, were predictive of both durable response and increased
      animal survival. These results demonstrate the increased efficacy of the CD-UPRT
      GDEPT compared to CD alone both biochemically and in a preclinical model and
      validate both 19F MRS and diffusion-weighted MRI as tools to assess gene function
      and therapeutic efficacy.

PMID- 15509510
TI  - Combination electro-gene therapy using herpes virus thymidine kinase and
      interleukin-12 expression plasmids is highly efficient against murine carcinomas
      in vivo.
AB  - We report the use of plasmid DNA-mediated combination gene therapy for tumor
      bearing mice using in vivo electroporation, also called electro-gene therapy
      (EGT), that resulted in uncomplicated and complete cures in more than 90% of the
      mice. Subcutaneously inoculated CT26 tumors in syngeneic BALB/c mice were
      subjected to repeated EGT treatments consisting of intratumoral co-injection of
      naked plasmids encoding the cytokine interleukin-12 (IL-12) (p35 and p40
      subunits) and the suicide gene herpes simplex virus thymidine kinase (HSV-tk),
      followed by in vivo electroporation. The early anti-tumor effect was always
      stronger, and the rate of cure, as seen in the long-term follow-up, was always
      greater in the groups treated with combination EGT than in those treated with IL
      12 or HSV-tk EGT alone. Systemic levels of IL-12 and IFN-gamma increased in both
      combination and IL-12-alone EGT-treated groups. Moreover, combination EGT for
      established subcutaneous tumors strongly reduced hematogenous lung metastases and
      increased survival time when live CT26 tumor cells were injected through the tail
      vein. Limited experiments on C57/B16 mice with murine melanoma also showed very
      similar trends. These results suggest that this simple and safe method of plasmid
      mediated combination EGT may provide a potentially effective gene therapy for
      cancer.

PMID- 15509511
TI  - Oncolytic effects of adenovirus mutant capable of replicating in hypoxic and
      normoxic regions of solid tumor.
AB  - Solid tumors contain normoxic and hypoxic regions depending on the distance from
      the capillary. Normal cells may also be exposed to hypoxia under certain
      physiological conditions. Tumor hypoxia has been shown to associate strongly with
      tumor propagation and malignant progression. Hypoxia-inducible factor (HIF)
      1alpha is stable under hypoxia and induces transcription of target genes by
      binding to the hypoxia-response element (HRE). Here we investigated the oncolytic
      effects of a novel adenovirus mutant with a deleted E1B55 gene (Ad.Delta55.HRE),
      in which the expression of E1A, which is essential for adenoviral replication, is
      regulated under the control of an HRE-expression system. Ad.Delta55.HRE expressed
      E1A under normoxia and more E1A under hypoxia and exhibited oncolytic effects on
      various cultured tumor cells, but its cytotoxic effect is relatively attenuated
      in normal fibroblast cells under normoxic and hypoxic conditions. Ad.Delta55.HRE
      lysed Huh-7 hepatoma cells stably expressing HIF-1alpha more effectively compared
      to parental cells. Ad.Delta55.HRE treatment exhibited significant antitumor
      activity in PC-3 prostate- and MDA-MB-435 breast tumor-bearing nude mice in which
      HIF-1alpha protein was immunohistochemically detected. The E1A and hexon proteins
      of adenovirus were immunostained in MDA-MB-435 xenografts after Ad.Delta55.HRE
      treatment, suggestive of viral replication. Our results suggest that
      Ad.Delta55.HRE may be useful for the treatment of solid tumors.

PMID- 15509512
TI  - Self-complementary adeno-associated virus 2 (AAV)-T cell protein tyrosine
      phosphatase vectors as helper viruses to improve transduction efficiency of
      conventional single-stranded AAV vectors in vitro and in vivo.
AB  - Recombinant vectors based on adeno-associated virus type 2 (AAV) target the liver
      efficiently, but the transgene expression is limited to approximately 5% of
      hepatocytes. The lack of efficient transduction is due, in part, to the presence
      of a cellular protein, FKBP52, phosphorylated forms of which inhibit the viral
      second-strand DNA synthesis. We have documented that dephosphorylation of FKBP52
      at tyrosine residues by the cellular T cell protein tyrosine phosphatase (TC-PTP)
      enhances AAV-mediated transduction in primary murine hematopoietic cells from TC
      PTP-transgenic mice. We have also documented that AAV-mediated transduction is
      significantly enhanced in hepatocytes in TC-PTP-transgenic as well as in FKBP52
      deficient mice because of efficient viral second-strand DNA synthesis. In this
      study, we evaluated whether co-infection of conventional single-stranded AAV
      vectors with self-complementary AAV-TC-PTP vectors leads to increased
      transduction efficiency of conventional AAV vectors in established human cell
      lines in vitro and in primary murine hepatocytes in vivo. We demonstrate here
      that scAAV-TC-PTP vectors serve as a helper virus in augmenting the transduction
      efficiency of conventional AAV vectors in vitro as well as in vivo which
      correlates directly with the extent of second-strand DNA synthesis of
      conventional single-stranded AAV vectors. Toxicological studies following tail
      vein injections of scAAV-TC-PTP vectors in experimental mice show no evidence of
      any adverse effect in any of the organs in any of the mice for up to 13 weeks.
      Thus, this novel co-infection strategy should be useful in circumventing one of
      the major obstacles in the optimal use of recombinant AAV vectors in human gene
      therapy.

PMID- 15509513
TI  - A phase I open-label, dose-escalation, multi-institutional trial of injection
      with an E1B-Attenuated adenovirus, ONYX-015, into the peritumoral region of
      recurrent malignant gliomas, in the adjuvant setting.
AB  - ONYX-015 is an oncolytic virus untested as a treatment for malignant glioma. The
      NABTT CNS Consortium conducted a dose-escalation trial of intracerebral
      injections of ONYX-015. Cohorts of six patients at each dose level received doses
      of vector from 10(7) plaque-forming units (pfu) to 10(10) pfu into a total of 10
      sites within the resected glioma cavity. Adverse events were identified on
      physical exams and testing of hematologic, renal, and liver functions. Efficacy
      data were obtained from serial MRI scans. None of the 24 patients experienced
      serious adverse events related to ONYX-015. The maximum tolerated dose was not
      reached at 10(10) pfu. The median time to progression after treatment with ONYX
      015 was 46 days (range 13 to 452 + days). The median survival time was 6.2 months
      (range 1.3 to 28.0 + months). One patient has not progressed and 1 patient showed
      regression of interval-increased enhancement. With more than 19 months of follow
      up, 1/6 recipients at a dose of 10(9) and 2/6 at a dose of 10(10) pfu remain
      alive. In 2 patients who underwent a second resection 3 months after ONYX-015
      injection, a lymphocytic and plasmacytoid cell infiltrate was observed. Injection
      of ONYX-015 into glioma cavities is well tolerated at doses up to 10(10) pfu.

PMID- 15509514
TI  - AdvHSV-tk gene therapy with intravenous ganciclovir improves survival in human
      malignant glioma: a randomised, controlled study.
AB  - Malignant glioma is a devastating brain tumor with no effective treatment. This
      randomised, controlled study involved 36 patients with operable primary or
      recurrent malignant glioma. Seventeen patients were randomized to receive AdvHSV
      tk gene therapy (3 x 10(10) pfu) by local injection into the wound bed after
      tumor resection, followed by intravenous ganciclovir (GCV), 5 mg/kg twice daily
      for 14 days. The control group of 19 patients received standard care consisting
      of radical excision followed by radiotherapy in those patients with primary
      tumors. The primary end-point was survival as defined by death or surgery for
      recurrence. Secondary end-points were all-cause mortality and tumour progression
      as determined by MRI. Overall safety and quality of life were also assessed.
      Findings were also compared with historical controls (n = 36) from the same unit
      over 2 years preceding the study. AdvHSV-tk treatment produced a clinically and
      statistically significant increase in mean survival from 39.0 +/- 19.7 (SD) to
      70.6 +/- 52.9 weeks (P = 0.0095, log-rank regression vs. randomized controls).
      The median survival time increased from 37.7 to 62.4 weeks. Six patients had
      increased anti-adenovirus antibody titers, without adverse effects. The treatment
      was well tolerated. It is concluded that AdvHSV-tk gene therapy with GCV is a
      potential new treatment for operable primary or recurrent high-grade glioma.

PMID- 15509515
TI  - Proteomics of the injured rat sciatic nerve reveals protein expression dynamics
      during regeneration.
AB  - Using proteomics, we investigated the temporal expression profiles of proteins in
      rat sciatic nerve after experimental crush. Extracts of sciatic nerves collected
      at 5, 10, and 35 days after injury were analyzed by two-dimensional gel
      electrophoresis and quantitative image analysis. Of the approximately 1,500
      protein spots resolved on each gel, 121 showed significant regulation during at
      least one time point. Using cluster analysis, these proteins were grouped into
      two expression profiles of down-regulation and four of up-regulation. These
      profiles mainly reflected differences in cellular origins in addition to
      different functional roles. Mass spectrometric analysis identified 82 proteins
      pertaining to several functional classes, i.e. acute-phase proteins, antioxidant
      proteins, and proteins involved in protein synthesis/maturation/degradation,
      cytoskeletal (re)organization, and in lipid metabolism. Several proteins not
      previously implicated in nerve regeneration were identified, e.g. translationally
      controlled tumor protein, annexin A9/31, vitamin D-binding protein, alpha
      crystallin B, alpha-synuclein, dimethylargininases, and reticulocalbin. Real-time
      PCR analysis of selected genes showed which were expressed in the nerve versus
      the dorsal root ganglion neurons. In conclusion, this study highlights the
      complexity and temporal aspect of the molecular process underlying nerve
      regeneration and points to the importance of glial and inflammatory determinants.

PMID- 15509516
TI  - Roles and regulation of stat family transcription factors in human breast cancer.
AB  - Stats (for signal transducers and activators of transcription) are a family of
      transcription factors that regulate cell growth and differentiation. Their
      activity is latent until phosphorylation by receptor-associated kinases. A
      sizable body of data from cell lines, mouse models, and human tissues now
      implicates these transcription factors in the oncogenesis of breast cancer.
      Because Stat activity is modulated by several posttranslational modifications and
      protein-protein interactions, these transcription factors are capable of
      integrating inputs from multiple signaling networks. Given this, the future
      utilization of Stats as prognostic markers and therapeutic targets in human
      breast cancer appears likely.

PMID- 15509517
TI  - Staying connected: synapses in Alzheimer disease.

PMID- 15509518
TI  - Subcellular topography of neuronal Abeta peptide in APPxPS1 transgenic mice.
AB  - In transgenic mice expressing human mutant beta-amyloid precursor protein (APP)
      and mutant presenilin-1 (PS1), Abeta antibodies labeled granules, about 1 microm
      in diameter, in the perikaryon of neurons clustered in the isocortex,
      hippocampus, amygdala, thalamus, and brainstem. The granules were present before
      the onset of Abeta deposits; their number increased up to 9 months and decreased
      in 15-month-old animals. They were immunostained by antibodies against Abeta 40,
      Abeta 42, and APP C-terminal region. In double immunofluorescence experiments,
      the intracellular Abeta co-localized with lysosome markers and less frequently
      with MG160, a Golgi marker. Abeta accumulation correlated with an increased
      volume of lysosomes and Golgi apparatus, while the volume of endoplasmic
      reticulum and early endosomes did not change. Some granules were immunolabeled
      with an antibody against flotillin-1, a raft marker. At electron microscopy,
      Abeta, APP-C terminal, cathepsin D, and flotillin-1 epitopes were found in the
      lumen of multivesicular bodies. This study shows that Abeta peptide and APP C
      terminal region accumulate in multivesicular bodies containing lysosomal enzymes,
      while APP N-terminus is excluded from them. Multivesicular bodies could
      secondarily liberate their content in the extracellular space as suggested by the
      association of cathepsin D with Abeta peptide in the extracellular space.

PMID- 15509519
TI  - alpha(2)-Macroglobulin: a novel cytochemical marker characterizing preneoplastic
      and neoplastic rat liver lesions negative for hitherto established cytochemical
      markers.
AB  - We tried to identify a novel marker characteristic for rat hepatocellular
      preneoplastic and neoplastic lesions, undetectable by well established
      cytochemical markers. Glutathione S-transferase placental (GST-P)-negative
      hepatocellular altered foci (HAF), hepatocellular adenoma (HCA), and
      hepatocellular carcinoma (HCC) were generated by two initiation-promotion models
      with N-nitrosodiethylamine (NDEN) and peroxisome proliferators, Wy-14,643 and
      clofibrate. Total RNAs isolated from laser-microdissected GST-P-negative HAF
      (amphophilic cell foci) and adjacent normal tissues were applied to microarray
      analysis. As a result, five up-regulated genes were identified, and further
      detailed examinations of the gene demonstrating most fluctuation, ie, that for
      alpha(2)-macroglobulin (alpha(2)M) were performed. In reverse transcriptase
      polymerase chain reaction, alpha(2)M mRNA was overexpressed not only in
      amphophilic GST-P-negative HAF but also in amphophilic GST-P-negative HCA and
      HCC. In situ hybridization showed accumulation of alpha(2)M mRNA to be evenly
      distributed within GST-P-negative HAF (predominantly amphophilic cell foci).
      Distinctive immunohistochemical staining for alpha(2)M could be consistently
      demonstrated in GST-P-negative HAF, HCA, and HCC induced not only by peroxisome
      proliferators but also N-nitrosodiethylamine alone. Thus our findings suggest
      that alpha(2)M is an important novel cytochemical marker to identify
      hepatocellular preneoplastic and neoplastic lesions, particularly amphophilic
      cell foci, undetectable by established cytochemical markers and is tightly linked
      to rat hepatocarcinogenesis.

PMID- 15509520
TI  - Colonic crypt changes during adenoma development in familial adenomatous
      polyposis: immunohistochemical evidence for expansion of the crypt base cell
      population.
AB  - Familial adenomatous polyposis patients, who have a germline APC mutation,
      develop adenomas in normal-appearing colonic mucosa, and in the process usually
      acquire a mutation in the other APC allele as well. Nonetheless, the cellular
      mechanisms that link these initiating genetic changes with the earliest tissue
      changes (upward shift in the labeling index) in colon tumorigenesis are unclear.
      Based on the tenet that colorectal cancer originates from crypt stem cells (SCs)
      and on our kinetic modeling, we hypothesized that overpopulation of mutant
      colonic SCs is the missing link. Directly testing this hypothesis requires
      measuring changes in the size of the SC population, but specific markers for
      human colonic SCs are lacking. Hence, we used immunohistochemical mapping to
      study crypt base cells, of which SCs are a subset. Using colectomy specimens from
      16 familial adenomatous polyposis and 11 control cases, we determined the
      topographic profiles of various cell populations along the crypt axis and the
      proportions of each cell type. In the formation of adenomatous crypts, the
      distribution of cells expressing crypt base cell markers (MSH2, Bcl-2, survivin)
      expanded toward the crypt surface and showed the greatest proportional increase
      (fivefold to eightfold). Cells expressing a marker for the upper crypt
      (p27(kip1)) shifted to the crypt bottom and showed the smallest increase. This
      suggests that: 1) during adenoma development, APC mutations cause expansion of
      the crypt base cell population, including crypt SCs; 2) SC overpopulation can
      explain the shifts in pattern of proliferative crypt cell populations in early
      colon tumorigenesis, and 3) mutant crypt SCs clonally expand to form colonic
      adenomas and carcinomas.

PMID- 15509521
TI  - Hepatitis C virus down-regulates insulin receptor substrates 1 and 2 through up
      regulation of suppressor of cytokine signaling 3.
AB  - The pathogenesis of hepatitis C virus (HCV)-associated insulin resistance remains
      unclear. Therefore, we investigated mechanisms for HCV-associated insulin
      resistance. Homeostasis model assessment for insulin resistance was increased in
      patients with HCV infection. An increase in fasting insulin levels was associated
      with the presence of serum HCV core, the severity of hepatic fibrosis and a
      decrease in expression of insulin receptor substrate (IRS) 1 and IRS2, central
      molecules of the insulin-signaling cascade, in patients with HCV infection. Down
      regulation of IRS1 and IRS2 was also seen in HCV core-transgenic mice livers and
      HCV core-transfected human hepatoma cells. Carbobenzoxy-l-leucyl-l-leucyl-l
      leucinal, a potent proteosomal proteolysis inhibitor, blocked down-regulation of
      IRS1 and IRS2 in HCV core-transfected hepatoma cells. In human hepatoma cells,
      HCV core up-regulated suppressor of cytokine signaling (SOCS) 3 and caused
      ubiquitination of IRS1 and IRS2. HCV core-induced down-regulation of IRS1 and
      IRS2 was not seen in SOCS3(-/-) mouse embryonic fibroblast cells. Furthermore,
      HCV core suppressed insulin-induced phosphorylation of p85 subunit of
      phosphatidylinositol 3-kinase and Akt, activation of 6-phosphofructo-2-kinase,
      and glucose uptake. In conclusion, HCV infection changes a subset of hepatic
      molecules regulating glucose metabolism. A possible mechanism is that HCV core
      induced SOCS3 promotes proteosomal degradation of IRS1 and IRS2 through
      ubiquitination.

PMID- 15509522
TI  - Loss of p53 sensitizes mice with a mutation in Ccm1 (KRIT1) to development of
      cerebral vascular malformations.
AB  - Cerebral cavernous malformations (CCM) consist of clusters of abnormally dilated
      blood vessels. Hemorrhaging of these lesions can cause seizures and lethal
      stroke. Three loci are associated with autosomal dominant CCM, and the causative
      genes have been identified for CCM1 and CCM2. We have generated mice with a
      targeted mutation of the Ccm1 gene, but an initial survey of 20 heterozygous mice
      failed to detect any cavernous malformations. To test the hypothesis that growth
      of cavernous malformations depends on somatic loss of heterozygosity at the Ccm1
      locus, we bred animals that were heterozygous for the Ccm1 mutation and
      homozygous for loss of the tumor suppressor Trp53 (p53), which has been shown to
      increase the rate of somatic mutation. We observed vascular lesions in the brains
      of 55% of the double-mutant animals but none in littermates with other genotypes.
      Although the genetic evidence suggested somatic mutation of the wild-type Ccm1
      allele, we were unable to demonstrate loss of heterozygosity by molecular
      methods. An alternative explanation is that p53 plays a direct role in formation
      of the vascular malformations. The striking similarity of the human and mouse
      lesions indicates that the Ccm1(+/-) Trp53(-/-) mice are an appropriate animal
      model of CCM.

PMID- 15509523
TI  - T-cell properties determine disease site, clinical presentation, and cellular
      pathology of experimental autoimmune encephalomyelitis.
AB  - Two distinct clinical phenotypes of experimental autoimmune encephalomyelitis are
      observed in BALB interferon-gamma knockout mice immunized with encephalitogenic
      peptides of myelin basic protein. Conventional disease, characterized by
      ascending weakness and paralysis, occurs with greater frequency after immunizing
      with a peptide comprising residues 59 to 76. Axial-rotatory disease,
      characterized by uncontrolled axial rotation, occurs with greater frequency in
      mice immunized with a peptide corresponding to exon 2 of the full length 21.5-kd
      protein. The two clinical phenotypes are histologically distinguishable.
      Conventional disease is characterized by inflammation and demyelination primarily
      in spinal cord, whereas axial-rotatory disease involves inflammation and
      demyelination of lateral medullary areas of brain. Both types have infiltrates in
      which neutrophils are a predominating component. By isolating T cells and
      transferring disease to naive recipients, we show here that the type of disease
      is determined entirely by the inducing T cell. Furthermore, studies using CXCR2
      knockout recipients, unable to recruit neutrophils to inflammatory sites, show
      that although neutrophils are critical for some of these T cells to effect
      disease, there are also interferon-gamma-deficient T cells that induce disease in
      the absence of both interferon-gamma and neutrophils. These results highlight the
      multiplicity of T-cell-initiated effector pathways available for inflammation and
      demyelination.

PMID- 15509524
TI  - Using siRNA technique to generate transgenic animals with spatiotemporal and
      conditional gene knockdown.
AB  - Based on the RNAi technique, we have developed a new approach that generates
      transgenic animals capable of mimicking human genetic diseases. The new system is
      a combination of siRNA with Cre-loxP and tetracycline-on. It has the
      characteristics of being stable, inheritable, and inducible, with the siRNA able
      to be transcribed tissue specifically. To support the ability of this new method
      to generate a model for a disease, we created an ABCA1-deficient mouse line that
      mimics Tangier disease under controlled conditions. Thus, it should now be
      possible to rapidly establish human genetic diseases as a whole animal model
      without the use of embryonic stem cell and gene targeting. This system also
      provides a tool for pathological and pharmacological studies of aspects peculiar
      to particular human genetic diseases.

PMID- 15509525
TI  - Heterogeneity in primary and metastatic prostate cancer as defined by cell
      surface CD profile.
AB  - Cluster designation (CD) antigens are cell surface markers that can be used to
      identify constituent cell populations of an organ. We have previously determined
      the CD phenotype of normal prostate parenchymal cells and are now extending this
      analysis to prostate cancer. Since expression of CD antigens is associated with
      cellular differentiation, cancer cells may differ from their normal counterpart
      in their CD profile. Compared with luminal secretory cells, prostate
      adenocarcinoma cells are frequently negative for CD10 and CD13, express increased
      levels of the cell activation molecule CD24, and decreased levels of the
      apoptosis-associated multifunctional enzyme CD38. Expression of CD57, CD63,
      CD75s, CD107a, CD107b, CD164, and CD166 by cancer cells is similar to that of
      secretory cells. Prostate basal epithelial cells do not express the CD antigens
      characteristic of prostate secretory cells; and the basal cell CD markers, CD29,
      CD44, CD49b, CD49f, CD104, and nerve growth factor receptor (NGFR) are not
      expressed by cancer cells. The preferential expression of secretory cell
      associated CD markers by prostate cancer cells suggests a closer lineage
      relationship between cancer cells and secretory cells than basal cells. Although
      the above cancer CD phenotype was the most frequently seen, some prostate cancers
      contained populations of CD10- and/or CD13-positive cells, and CD57-negative
      cells. Furthermore, the cancer phenotype of tumor metastasis is different.
      Despite its low frequency in primary tumors, CD10 is expressed by virtually all
      of the nodal metastases of prostate cancer. In addition, stromal fibromuscular
      cells associated with primary prostate cancer differ from stromal cells in benign
      prostate tissue by an increased level of expression of the cell activation
      molecule, CD90. In summary, our data show that the CD marker expression profile
      of prostate cancer cells most closely resembles that of secretory prostate
      epithelial cells and that some prostate cancers consist of heterogeneous cell
      populations as distinguished by CD-marker expression profiles.

PMID- 15509526
TI  - Angiopoietin-1 promotes tumor angiogenesis in a rat glioma model.
AB  - Angiopoietins have been implicated in playing an important role in blood vessel
      formation, remodeling, maturation, and maintenance. However, the role of
      angiopoietins in tumor angiogenesis remains uncertain. In this study, expression
      of human angiopoietin-1 (hAng-1) and angiopoietin (hAng-2) was amplified in the
      rat glioma cell line GS9L by stable transfection using an inducible tet-off
      system. Transfected cells were implanted intracerebrally into syngenic Fischer
      344 rats. We demonstrated by means of magnetic resonance imaging that increased
      hAng-1 expression promoted a significant in vivo growth of intracerebral gliomas
      in rats. Overexpression of hAng-1 resulted in more numerous, more highly branched
      vessels, which were covered by pericytes. On the other hand, tumors derived from
      hAng-2-overexpressing cells were smaller than empty-plasmid control tumors. The
      tumor vasculature in these tumors was composed of aberrant small vascular cords,
      which were associated with few mural cells. Our results indicate that in the
      presence of hAng-1, tumors induce a more functional vascular network, which led
      to better tumor perfusion and growth. On the other hand, overexpression of hAng-2
      led to less intact tumor vessels, inhibited capillary sprouting, and impaired
      tumor growth.

PMID- 15509527
TI  - Enhanced expression of CD44 variants in human atheroma and abdominal aortic
      aneurysm: possible role for a feedback loop in endothelial cells.
AB  - CD44, a polymorphic hyaluronate receptor, may participate in chronic
      inflammation. We hypothesized that CD44 variants contribute to the development of
      arterial diseases. CD44 levels vary in normal and diseased arterial tissues in
      the following order: unaffected arteries < fibrous plaques < or = abdominal
      aortic aneurysm < atheromatous plaques; and correlate with macrophage content.
      Furthermore, plaque microvessels express CD44, and anti-CD44v3 or anti-CD44v6
      treatment reduces endothelial cell proliferation but not apoptosis in vitro,
      suggesting functionality of these receptors. Endothelial cells express CD44H and
      CD44v6 after exposure to interleukin-1beta and tumor necrosis factor-alpha.
      Macrophages, a major source of abundant CD44 in vitro, express not only CD44H but
      also variants CD44v4/5, CD44v6, and CD44v7/8, isoforms distinctively regulated by
      proinflammatory cytokines. Several proinflammatory cytokines induce shedding of
      CD44 from the surface of macrophages and endothelial cells. Soluble CD44
      stimulates the expression and release of interleukin-1beta from endothelial
      cells, suggesting a positive feedback loop of this cytokine. By demonstrating
      augmented expression of CD44 and variants within human atheroma and in abdominal
      aortic aneurysm as well as the vascular cell release of sCD44, a process
      regulated by proinflammatory cytokines, this study provides new insights on the
      functions of CD44 in arterial diseases.

PMID- 15509528
TI  - Rheumatic heart disease: proinflammatory cytokines play a role in the progression
      and maintenance of valvular lesions.
AB  - Heart lesions of rheumatic heart disease (RHD) patients contain T-cell clones
      that recognize heart proteins and streptococcal M peptides. To functionally
      characterize heart-infiltrating T lymphocytes, we evaluated their cytokine
      profile, both directly in situ and in T-cell lines derived from the heart (HIL).
      Interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-4,
      and IL-10 expressions were characterized in 20 heart tissue infiltrates from 14
      RHD patients by immunohistochemistry. IFN-gamma-, TNF-alpha-, and IL-10-positive
      cells were consistently predominant, whereas IL-4 was scarce in the valves. In
      agreement with these data, the in vitro experiments, in which 13 HILs derived
      from heart samples of eight patients were stimulated with M5 protein and the
      immunodominant M5 (81-96) peptide, IL-4 was detected in HIL derived from the
      atrium (three of six) but not from the valve (zero of seven). IFN-gamma and IL-10
      production were detected in culture supernatants in 11 of 13 and 6 of 12 HILs,
      respectively. The predominant IFN-gamma and TNF-alpha expression in the heart
      suggests that Th1-type cytokines could mediate RHD. Unlike in reversible
      myocardium inflammation, the significantly lower IL-4 expression in the valvular
      tissue (P = 0.02) may contribute to the progression of the RHD leading to
      permanent valvular damage (relative risk, 4.3; odds ratio, 15.8). The lack of IL
      4 in vitro production by valve-derived HIL also emphasizes the more severe tissue
      destruction in valves observed in RHD.

PMID- 15509529
TI  - Gender, age, and season at immunization uniquely influence the genetic control of
      susceptibility to histopathological lesions and clinical signs of experimental
      allergic encephalomyelitis: implications for the genetics of multiple sclerosis.
AB  - Multiple sclerosis (MS), the principal inflammatory demyelinating disease of the
      central nervous system (CNS), is believed to have an immunopathological etiology
      arising from gene-environment interactions. In this study, we examined the effect
      of sex, age, and season at immunization on the susceptibility of (B10.S x SJL/J)
      F(2) intercross mice to experimental allergic encephalomyelitis (EAE), the
      foremost animal model of MS. Results of logistic regression analyses suggest that
      female mice were more likely to exhibit CNS lesions than male mice [odds ratio
      (OR) = 2.28 for brain lesions; OR = 2.37 for spinal cord (SC) lesions]. Although
      statistically significant associations were seen between brain and SC lesions and
      age at the time of injection or month of injection when examined separately;
      these associations disappeared when controlling for sex in multiple logistic
      regression analyses. These results suggest that the sex of the mouse is more
      important in influencing the development of brain and SC lesions than was either
      age or month of immunization. When examining clinical disease as the endpoint,
      the OR for the age at immunization is 1.04, indicating that the odds of being
      affected increase by 4% for each increasing week of age. When controlled for age,
      the OR for injection in the summer months (July through September) is 1.90,
      suggesting that the odds of being clinically affected are 90% greater for F(2)
      intercross animals injected in the summercompared to those injected in the winter
      to spring months (February through May). In contrast to CNS lesions, the age and
      season at immunization significantly and independently influenced susceptibility
      to clinical EAE and did so equally in both males and females. Linkage analysis to
      eae5, the H2-linked locus controlling susceptibility to clinical disease, was
      performed using 6- to 12- and >12-week-old cohorts as well as summer and
      winter/spring cohorts of F(2) mice. Significant linkage of clinical EAE to eae5
      was observed with the 6- to 12-week-old and summer populations. In contrast,
      linkage of clinical EAE to eae5 was not detected with the >12-week-old and
      winter/spring populations. These results indicate that age and seasonal effects
      are capable of overriding eae5-dependent genetic control of susceptibility to
      clinical EAE and have significant implications for the genetics of MS.

PMID- 15509530
TI  - Lack of the growth factor midkine enhances survival against cisplatin-induced
      renal damage.
AB  - Although cisplatin acts directly on proximal tubule epithelial cells and causes
      cell death, little is known regarding the biological significance of its
      secondary effects, such as inflammation. The growth factor midkine is highly
      expressed in the proximal tubule and exerts ambivalent activities as to cisplatin
      nephrotoxicity, ie, anti-apoptotic and chemotactic ones. Here we report that
      midkine-deficient mice show a significantly higher survival rate than wild-type
      mice. The levels of blood urea nitrogen and tubular degeneration and apoptosis
      were higher in wild-type mice despite the anti-apoptotic activity of midkine. We
      found that recruitment of neutrophils was more enhanced in wild-type mice, this
      being consistent with the chemotactic activity of midkine. Midkine expression in
      wild-type mice persisted for 24 hours, and then dramatically decreased.
      Preadministration of midkine anti-sense oligodeoxyribonucleotide to wild-type
      mice suppressed midkine expression, and consequently neutrophil infiltration. It
      is of note that neutrophil infiltration, apoptosis, and elevation of blood urea
      nitrogen became conspicuous sequentially, namely 1, 2, and 3 days after cisplatin
      administration, respectively. These findings suggest that early molecular events
      involving midkine induce inflammatory response and their circuits eventually
      enhance the death of the proximal tubule epithelial cells. The results indicate
      the crucial role of inflammation in cisplatin-induced renal damage, and provide a
      candidate molecular target for its prevention.

PMID- 15509531
TI  - Tumor necrosis factor-related apoptosis-inducing ligand can induce apoptosis in
      subsets of premalignant cells.
AB  - During the transformation from a normal to a malignant cell, several mutations
      are required to bypass the pathways responsible for controlling proliferation.
      Premalignant cells have acquired some, but not all of these mutations and
      consequently have not yet attained a malignant phenotype characterized by tumor
      formation in vivo. Tumor necrosis factor-related apoptosis-inducing ligand
      (TRAIL) can induce apoptosis in malignant cells while sparing normal ones and is
      currently being considered as adjuvant therapy for various human malignancies.
      Whether TRAIL is effective in inducing apoptosis in premalignant cells is
      unclear, however. We studied the effect of TRAIL on two human premalignant cell
      lines the SV7tert and HA1E cells. Both cell lines had been immortalized by the
      addition of simian virus 40 large T antigen and the telomerase subunit hTERT, but
      had not been transformed into malignant cells. TRAIL initiated apoptosis by
      activating both the mitochondrial-independent and -dependent apoptotic pathways
      in both cell lines at relatively low doses whereas it had no effect on normal
      human pulmonary artery smooth muscle cells even at high doses. These results
      suggest that TRAIL can induce apoptosis in premalignant cells and suggests a
      novel therapy for the treatment of premalignant lesions in vivo.

PMID- 15509532
TI  - beta-site amyloid precursor protein cleaving enzyme 1 increases amyloid
      deposition in brain parenchyma but reduces cerebrovascular amyloid angiopathy in
      aging BACE x APP[V717I] double-transgenic mice.
AB  - The generation of amyloid peptides (Abeta) from the amyloid precursor protein
      (APP) is initiated by beta-secretase (BACE), whereas subsequent gamma-secretase
      cleavage mediated by presenilin-1, produces Abeta peptides mainly of 40 or 42
      amino acids long. In addition, alternative beta'-cleavage of APP at position 11
      of the amyloid sequence results in N-truncated Abeta(11-40/42) peptides, but the
      functional significance or pathological impact is unknown. Here we demonstrate
      that in the brain of BACE x APP[V717I] double-transgenic mice, amyloidogenic
      processing at both Asp1 and Glu11 is increased resulting in more and different
      Abeta species and APP C-terminal fragments. Pathologically, BACE significantly
      increased the number of diffuse and senile amyloid plaques in old double
      transgenic mice. Unexpectedly, vascular amyloid deposition was dramatically lower
      in the same BACE x APP[V717I] double-transgenic mice, relative to sex- and age
      matched APP[V717I] single-transgenic mice in the same genetic background. The
      tight inverse relation of vascular amyloid to the levels of the less soluble N
      terminally truncated Abeta peptides is consistent with the hypothesis that
      vascular amyloid deposition depends on drainage of excess tissue Abeta. This
      provides biochemical evidence in vivo for the preferential contribution of N
      truncated Abeta to parenchymal amyloid deposition in contrast to vascular amyloid
      pathology.

PMID- 15509533
TI  - PITX2 gain-of-function in Rieger syndrome eye model.
AB  - The human autosomal-dominant disorder Axenfeld-Rieger syndrome presents with
      defects in development of the eyes, teeth, and umbilicus. The eye manifests with
      iris ruptures, irido-corneal adhesions, cloudy corneas, and glaucoma.
      Transcription factors such as PITX2 and FOXC1 have been found to carry point
      mutations, causing the disorder. However, for approximately 40% of the cases, the
      pathogenesis is unknown. It has been reported that some mutations in PITX2
      increase transactivation, whereas most mutations cause defects in DNA binding or
      transactivation. It is not known whether up-regulation of PITX2 activity can
      cause the disorder as well. Here we test this hypothesis directly by
      overexpressing PITX2A as a transgene in mouse corneal mesenchyme and iris, using
      keratocan-flanking sequences. The mice presented with corneal opacification,
      corneal hypertrophy, irido-corneal adhesions, and severely degenerated retina,
      resembling glaucoma. The corneal hypertrophy also resembles the corneal
      hypertrophy of Pitx2-/- mice. Control transgenic mice carrying point mutations
      T68P or K88E in PITX2A were normal. These findings indicate a novel pathogenetic
      mechanism in which excess corneal and iridal PITX2A cause glaucoma and anterior
      defects that closely resemble Axenfeld-Rieger syndrome.

PMID- 15509534
TI  - Induction of inflammatory mediators and microglial activation in mice transgenic
      for mutant human P301S tau protein.
AB  - Mice transgenic for human P301S tau protein exhibit many characteristics of the
      human tauopathies, including the formation of abundant filaments made of
      hyperphosphorylated tau protein and neurodegeneration leading to nerve cell loss.
      At 5 months of age, the pathological changes are most marked in brainstem and
      spinal cord. Here we show that these changes are accompanied by marked
      neuroinflammation. Many tau-positive nerve cells in brainstem and spinal cord
      were strongly immunoreactive for interleukin-1beta and cyclooxygenase-2,
      indicating induction and overproduction of proinflammatory cytokines and enzymes.
      In parallel, numerous activated microglial cells were present throughout brain
      and spinal cord of transgenic mice, where they concentrated around tau-positive
      nerve cells. These findings suggest that inflammation may play a significant role
      in the events leading to neurodegeneration in the tauopathies and that anti
      inflammatory compounds may have therapeutic potential.

PMID- 15509535
TI  - Effects of angiotensin II receptor signaling during skin wound healing.
AB  - The tissue angiotensin (Ang) system, which acts independently of the circulating
      renin Ang system, is supposed to play an important role in tissue repair in the
      heart and kidney. In the skin, the role of the system for wound healing has
      remained to be ascertained. Our study demonstrated that oral administration of
      selective AngII type-1 receptor (AT(1)) blocker suppressed keratinocyte re
      epithelization and angiogenesis during skin wound healing in rats.
      Immunoprecipitation and Western blot analysis indicated the existence of AT(1)
      and AngII type-2 receptor (AT(2)) in cultured keratinocytes and myofibroblasts.
      In a bromodeoxyuridine incorporation study, induction of AT(1) signaling enhanced
      the incorporation into keratinocytes and myofibroblasts. Wound healing migration
      assays revealed that induction of AT(1) signaling accelerated keratinocyte re
      epithelization and myofibroblasts recovering. In these experiments, induction of
      AT(2) signaling acted vice versa. Taken together, our study suggests that skin
      wound healing is regulated by balance of opposing signals between AT(1) and
      AT(2).

PMID- 15509536
TI  - Severity of lung injury in cyclooxygenase-2-deficient mice is dependent on
      reduced prostaglandin E(2) production.
AB  - Levels of prostaglandin E(2) (PGE(2)), a potent inhibitor of fibroblast function,
      are decreased in the lungs of patients with pulmonary fibrosis, which has been
      shown to be because of limited expression of cyclooxygenase-2 (COX-2). To further
      investigate the relative importance of COX-2 and PGE(2) in the development of
      fibrosis we have used a selective COX-2 inhibitor and COX-2-deficient ((-/-) and
      (+/-)) mice in studies of bleomycin-induced lung fibrosis. We demonstrate in wild
      type mice that bleomycin-induced lung PGE(2) production is predominantly COX-2
      mediated. Furthermore, COX-2(+/-) mice show limited induction of PGE(2) and an
      enhanced fibrotic response with increased lung collagen content compared with
      wild-type mice after bleomycin injury (P < 0.001). In contrast, COX-2(-/-) mice
      show increased levels of lung PGE(2), compared with wild-type mice after injury
      (P < 0.05), because of compensatory up-regulation of COX-1, which appears to be
      associated with macrophage/monocytes but not fibroblasts derived from these mice.
      COX-2(-/-) mice show an enhanced and persistent inflammatory response to
      bleomycin, however the fibrotic response to injury was unaltered compared with
      wild-type animals. These data provide further direct evidence for the importance
      of up-regulating COX-2 and PGE(2) expression in protecting against the
      development of fibrosis after lung injury.

PMID- 15509537
TI  - The mannose-binding lectin-pathway is involved in complement activation in the
      course of renal ischemia-reperfusion injury.
AB  - Ischemia-reperfusion (I/R) is an important cause of acute renal failure (ARF).
      The complement system appears to be essentially involved in I/R injury. However,
      via which pathway the complement system is activated and in particular whether
      the mannose-binding lectin (MBL)-pathway is activated is unclear. This tempted us
      to study the activation and regulation of the MBL-pathway in the course of
      experimental renal I/R injury and in clinical post-transplant ARF. Mice subjected
      to renal I/R displayed evident renal MBL-depositions, depending on the duration
      of warm ischemia, in the early reperfusion phase. Renal deposition of C3, C6 and
      C9 was observed in the later reperfusion phase. The deposition of MBL-A and -C
      completely co-localized with the late complement factor C6, showing that MBL is
      involved in complement activation in the course of renal I/R injury. Moreover,
      the degree of early MBL-deposition correlated with complement activation,
      neutrophil-influx, and organ-failure observed in the later reperfusion phase. In
      serum of mice subjected to renal I/R MBL-A, levels increased in contrast to MBL-C
      levels, which dropped evidently. In line, liver mRNA levels for MBL-A increased,
      whereas MBL-C levels decreased. Renal MBL mRNA levels rapidly dropped in the
      course of renal I/R. Finally, in human biopsies, MBL-depositions were observed
      early after transplantation of ischemically injured kidneys. In line with our
      experimental data, in ischemically injured grafts displaying post-transplant
      organ-failure extensive MBL depositions were observed in peritubular capillaries
      and tubular epithelial cells. In conclusion, in experimental renal I/R injury and
      clinical post-transplant ARF the MBL-pathway is activated, followed by activation
      of the complement system. These data indicate that the MBL-pathway is involved in
      ischemia-induced complement activation.

PMID- 15509538
TI  - Hypermethylation of growth arrest DNA damage-inducible gene 45 beta promoter in
      human hepatocellular carcinoma.
AB  - Growth arrest DNA damage-inducible gene 45 beta (GADD45beta) has been known to
      regulate cell growth, apoptotic cell death, and cellular response to DNA damage.
      Down-regulation of GADD45beta has been verified to be specific in hepatocellular
      cancer (HCC) and consistent with the p53 mutant, and degree of malignancy of HCC.
      This observation was further confirmed by eight HCC cell lines and paired human
      normal and HCC tumor tissues by Northern blot and immunohistochemistry. To better
      understand the transcription regulation, we cloned and characterized the active
      promoter region of GADD45beta in luciferase-expressing vector. Using the
      luciferase assay, three nuclear factor-kappaB binding sites, one E2F-1 binding
      site, and one putative inhibition region were identified in the proximal promoter
      of GADD45beta from -865/+6. Of interest, no marked putative binding sites could
      be identified in the inhibition region between -520/-470, which corresponds to
      CpG-rich region. The demethylating agent 5-Aza-dC was used and demonstrated
      restoration of the GADD45beta expression in HepG2 in a dose-dependent manner. The
      methylation status in the promoter was further examined in one normal liver cell,
      eight HCC cell lines, eight HCC tissues, and five corresponding nonneoplastic
      liver tissues. Methylation-specific polymerase chain reaction and sequencing of
      the sodium bisulfite-treated DNA from HCC cell lines and HCC samples revealed a
      high percentage of hypermethylation of the CpG islands. Comparatively, the five
      nonneoplastic correspondent liver tissues demonstrated very low levels of
      methylation. To further understand the functional role of GADD45beta under
      expression in HCC the GADD45beta cDNA constructed plasmid was transfected into
      HepG2 (p53 WT) and Hep3B (p53 null) cells. The transforming growth factor-beta
      was assayed by enzyme-linked immunosorbent assay, which revealed a decrease to
      40% in transfectant of HepG2, but no significant change in Hep3B transfectant.
      Whereas, Hep3B co-transfected with p53 and GADD45beta demonstrated significantly
      reduced transforming growth factor-beta. The colony formation was further
      examined and revealed a decrease in HepG2-GADD45beta transfectant and Hep3B
      p53/GADD45beta co-transfectant. These findings suggested that methylation might
      play a crucial role in the epigenetic regulation of GADD45beta in hepatocyte
      transformation that may be directed by p53 status. Thus, our results provided a
      deeper understanding of the molecular mechanism of GADD45beta down-regulation in
      HCC.

PMID- 15509539
TI  - Dysregulation of stathmin, a microtubule-destabilizing protein, and up-regulation
      of Hsp25, Hsp27, and the antioxidant peroxiredoxin 6 in a mouse model of familial
      amyotrophic lateral sclerosis.
AB  - Gain-of-function mutations of the Cu/Zn superoxide dismutase (SOD1) gene cause
      dominantly inherited familial amyotrophic lateral sclerosis. The identification
      of differentially regulated proteins in spinal cords of paralyzed mice expressing
      SOD1(G93A) may contribute to understanding mechanisms of toxicity by mutant SOD1.
      Protein profiling showed dysregulation of Stathmin with a marked decrease of its
      most acidic and phosphorylated isoform, and up-regulation of heat shock proteins
      25 and 27, peroxiredoxin 6, phosphatidylinositol transfer protein-alpha,
      apolipoprotein E, and ferritin heavy chain. Stathmin accumulated in the cytoplasm
      of 30% of spinal cord motor neurons with fragmented Golgi apparatus.
      Overexpression of Stathmin in HeLa cells was associated with collapse of
      microtubule networks and Golgi fragmentation. These results, together with the
      decrease of one Stathmin isoform, suggest a role of the protein in Golgi
      fragmentation. Mutant SOD1 co-precipitated and co-localized with Hsp25 in neurons
      and astrocytes. Mutant SOD1 may thus deprive cells of the anti-apoptotic and
      other protective activities of Hsp25. Astrocytes contained peroxiredoxin 6, a
      unique nonredundant antioxidant. The up-regulation of peroxiredoxin 6 probably
      constitutes a defense to oxidative stress induced by SOD1(G93A). Direct effects
      of SOD1(G93A) or sequential reactions triggered by the mutant may cause the
      protein changes.

PMID- 15509540
TI  - Biliary dysgenesis in the PCK rat, an orthologous model of autosomal recessive
      polycystic kidney disease.
AB  - Hepatic polycystic disease occurs alone or in combination with polycystic kidney
      disease (PKD). In autosomal recessive PKD (ARPKD), liver lesions are the major
      cause of morbidity and mortality in older patients. ARPKD is caused by a mutation
      to PKHD1 and the PCK rat is an orthologous model of disease. Recently, we showed
      that fibrocystin, Pkhd1 protein, is localized to primary cilia in rat
      cholangiocytes and that disruption of its ciliary expression results in biliary
      cystogenesis. This study describes biliary phenotype in the PCK rat using micro
      computed tomography scanning and three-dimensional reconstruction, and light,
      scanning, and transmission microscopy. Our results show that the biliary tree
      undergoes extensive remodeling resulting in bile duct dilatation, focal budding,
      and formation of cysts that are initially connected to bile ducts, but throughout
      time separate from them. Progressive liver enlargement results from massive cyst
      formation while liver parenchymal volume remains unchanged. Cilia in cystic cells
      are abnormal consistent with the notion that the primary defect in ARPKD
      resulting in cystogenesis may be linked to ciliary dysfunction. Our results
      suggest that the PCK rat is a useful model for studies of biliary cystogenesis
      and treatment options of inherited cystic liver disease.

PMID- 15509541
TI  - Deletion of murine Smn exon 7 directed to liver leads to severe defect of liver
      development associated with iron overload.
AB  - Spinal muscular atrophy (SMA) is characterized by degeneration of lower motor
      neurons caused by mutations of the survival motor neuron 1 gene (SMN1). SMN is
      involved in various processes including the formation of the spliceosome, pre
      mRNA splicing and transcription. To know whether SMN has an essential role in all
      mammalian cell types or an as yet unknown specific function in the neuromuscular
      system, deletion of murine Smn exon 7, the most frequent mutation found among SMA
      patients, has been restricted to liver. Homozygous mutation results in severe
      impairment of liver development associated with iron overload and lack of
      regeneration leading to dramatic liver atrophy and late embryonic lethality of
      mutant mice. These data strongly suggest an ubiquitous and essential role of full
      length SMN protein in various mammalian cell types. In SMA patients, the residual
      amount of SMN allows normal function of various organs except motor neurons.
      However, data from mouse and human suggest that other tissues might be involved
      in severe form of SMA or during prolonged disease course which reinforce the need
      of therapeutic approaches targeted to all tissues. In addition, liver function of
      patients should be carefully investigated and followed up before and during
      therapeutic trials.

PMID- 15509542
TI  - ADAM12 is selectively overexpressed in human glioblastomas and is associated with
      glioblastoma cell proliferation and shedding of heparin-binding epidermal growth
      factor.
AB  - ADAMs (a disintegrin and metalloproteinases) are multifunctional molecules
      involved in cell-cell fusion, cell adhesion, membrane protein shedding, and
      proteolysis. In the present study, we examined the mRNA expression of 13
      different ADAM species with putative metalloproteinase activity in human
      astrocytic tumors, nonneoplastic brain tissues, and other intracranial tumors by
      reverse transcriptase-polymerase chain reaction, and found that prototype
      membrane-anchored ADAM12 (ADAM12m) is predominantly expressed in glioblastomas.
      Real-time quantitative polymerase chain reaction indicated that the expression
      level of ADAM12m is remarkably at least 5.7-fold higher in glioblastomas (n = 16)
      than in nonneoplastic brain tissues (n = 6), low grade (n = 7) and anaplastic
      astrocytic tumors (n = 9) (P < 0.05 for each group), and intracranial neurinomas
      (n = 5) (P < 0.01). In situ hybridization showed that glioblastoma cells are
      responsible for the gene expression. By immunohistochemistry, ADAM12m was
      predominantly immunolocalized on the cell membranes of glioblastoma cells.
      Immunoblotting analysis demonstrated that ADAM12m is expressed as an activated N
      glycosylated form of approximately 90 kd in glioblastoma tissues. There was a
      direct correlation between the mRNA expression levels of ADAM12m and
      proliferative activity (MIB1-positive cell index) of gliomas (r = 0.791, P <
      0.0001; n = 32). Protein bands consistent with the soluble form of heparin
      binding epidermal growth factor, a substrate of ADAM12m, were observed by
      immunoblotting in glioblastoma samples with the ADAM12m expression, and inhibited
      by treatment with ADAM inhibitor of the glioblastomas. These data demonstrate for
      the first time that among the 13 different ADAM species, ADAM12m is highly
      expressed in human glioblastomas, and suggest the possibility that ADAM12m plays
      a role in the prominent proliferation of the glioblastomas through shedding of
      heparin-binding epidermal growth factor.

PMID- 15509543
TI  - Calcineurin A-alpha but not A-beta is required for normal kidney development and
      function.
AB  - Calcineurin is an important signaling molecule in the kidney and may be involved
      in a variety of processes. The phosphatase subunit of calcineurin (CnA) has three
      isoforms, alpha, beta, and gamma. In this study, we investigated the effect of
      loss of calcineurin A-alpha (CnA-alpha) or calcineurin A-beta (CnA-beta) on the
      development and function of the kidney. Total calcineurin expression and activity
      was significantly reduced in whole kidney homogenates from both CnA-alpha -/- and
      CnA-beta -/- mice. Kidneys of CnA-beta -/- mice appear normal and the mice
      develop with no phenotypic abnormalities. In contrast, kidneys of CnA-alpha -/-
      animals fail to fully develop. In particular, postnatal maturation of the
      nephrogenic zone (NZ) is defective. Within the NZ, glomeruli also fail to mature
      and lack mesangial cells. In addition to alterations in development, there is an
      absence of proliferation and an increase of cell death in the NZ with loss of CnA
      alpha. Finally, increased collagen deposition is observed and serum creatinine
      levels are significantly increased in CnA-alpha -/- animals compared to wild-type
      littermates, indicating that kidney function is impaired. In summary, absence of
      CnA-alpha but not CnA-beta leads to a defect in normal maturation of the NZ and
      glomeruli, alterations in the cell cycle, and impaired kidney function.

PMID- 15509544
TI  - Bone marrow-derived cells contribute to epithelial engraftment during wound
      healing.
AB  - Recent findings suggest that bone marrow-derived cells (BMDC) may contribute to
      tissue maintenance throughout the body. However, it is not yet known whether
      marrow-derived epithelial cells are capable of undergoing proliferation. Our
      laboratory has shown that BMDC engraft as keratinocytes in the skin at low levels
      (</= 1%) in the absence of injury. Here we show that skin damage affects the
      degree of engraftment of BMDC as keratinocytes and that the keratinocytes are
      actively cycling. Female mice reconstituted with sex-mismatched BM were wounded
      by punch biopsy and incision. At the wound site, engraftment of BMDC as epidermal
      cells increased within 1 day, and continued to increase to approximately 4% by 3
      weeks after injury. Using a Cre-lox system, fusion of BMDC with epithelial cells
      was ruled out. BMDC-derived epithelial cells at the wound edges expressed Ki67, a
      marker for actively cycling cells, and this proliferation correlated with an
      increase in the number of donor-derived cells within the wound. Donor-derived
      cytokeratin 5-expressing cells were rare, suggesting that BMDC do not engraft as
      epidermal stem cells, and the level of engraftment peaked and then decreased over
      time, further suggesting that BMDC may assist in early wound healing by
      engrafting as transit-amplifying cells, which then differentiate into
      keratinocytes.

PMID- 15509545
TI  - USP6 and CDH11 oncogenes identify the neoplastic cell in primary aneurysmal bone
      cysts and are absent in so-called secondary aneurysmal bone cysts.
AB  - Aneurysmal bone cyst (ABC) is a locally recurrent bone lesion that has been
      regarded as a reactive process. Recently, a neoplastic basis in primary ABC was
      evidenced by demonstration of clonal chromosome band 17p13 translocations that
      place the USP6 (TRE2 or TRE17) oncogene under the regulatory influence of the
      highly active CDH11 promoter. Herein, we report CDH11 and/or USP6 rearrangements
      in 36 of 52 primary ABCs (69%), of which 10 had CDH11-USP6 fusion, 23 had variant
      USP6 rearrangements without CDH11 rearrangement, and three had variant CDH11
      rearrangements without USP6 rearrangement. USP6 and CDH11 rearrangements were
      restricted to spindle cells in the ABC and were not found in multinucleated giant
      cells, inflammatory cells, endothelial cells, or osteoblasts. CDH11 and USP6
      rearrangements did not correlate with recurrence-free survival, or with other
      clinicopathological features. CDH11 and USP6 rearrangements were not found in any
      of 17 secondary ABC associated with giant cell tumor, chondroblastoma,
      osteoblastoma, and fibrous dysplasia. These findings demonstrate that primary ABC
      are mesenchymal neoplasms exhibiting USP6 and/or CDH11 oncogenic rearrangements.
      By contrast, secondary ABC lack CDH11 and USP6 rearrangements, and although
      morphological mimics of primary ABC, appear to represent a non-specific
      morphological pattern of a diverse group of non-ABC neoplasms.

PMID- 15509546
TI  - CEACAM1 enhances invasion and migration of melanocytic and melanoma cells.
AB  - Expression of the cell adhesion molecule CEACAM1 in melanomas is an independent
      factor for the risk of metastasis with a predictive value superior to that of
      tumor thickness. We have previously shown that CEACAM1 co-localizes at the tumor
      stroma interface of invading melanoma masses with integrin beta(3) and that these
      two adhesion molecules interact via the CEACAM1 cytoplasmic domain. To address
      the functional consequences of CEACAM1 expression, we investigated invasion and
      migration of melanocytic and melanoma cells that stably express CEACAM1 using two
      different in vitro systems. Here, we demonstrate that CEACAM1 expression markedly
      enhances cell invasion and migration. The enhanced invasion and migration of
      CEACAM1-transfected cells was dependent on the presence of Tyr-488 within the
      full-length cytoplasmic CEACAM1 domain. Treatment with anti-CEACAM monoclonal
      antibodies blocked CEACAM1-enhanced cell invasion and cell migration in a dose
      dependent manner. Furthermore, the enhanced invasion and migration of CEACAM1
      transfected melanoma cells was blocked by integrin-antagonizing RGD peptides.
      Expression of integrin beta(3) induces the up-regulation of CEACAM1 in
      melanocytic MEL6 cells. These results strengthen the view that CEACAM1 and
      alpha(v)beta(3) integrin are functionally interconnected with respect to the
      invasive growth of melanomas.

PMID- 15509547
TI  - The glomerulosclerosis of aging in females: contribution of the proinflammatory
      mesangial cell phenotype to macrophage infiltration.
AB  - Age-associated renal changes may be an important cause of renal failure. We
      recently found that aged female B6 mice developed progressive glomerular lesions.
      This was associated with macrophage infiltration, a frequent finding in
      glomerulosclerosis. We used these mice as a model for studying the mechanisms of
      glomerular aging. We compared the gene expression profile of intact glomeruli
      from late postmenopausal (28-month-old) mice to that of intact glomeruli from
      premenopausal (5-month-old) mice. We found that inflammation-related genes,
      especially those expressed by activated macrophages, were up-regulated in the
      glomeruli of 28-month-old mice, a result correlating with the histological
      observation of glomerular macrophage infiltration. The mechanism for macrophage
      recruitment could have been stable phenotypic changes in mesangial cells because
      we found that mesangial cells isolated from 28-month-old mice expressed higher
      levels of RANTES and VCAM-1 than cells from 5-month-old mice. The elevated serum
      tumor necrosis factor (TNF)-alpha levels present in aged mice may contribute to
      increased RANTES and VCAM-1 expression in mesangial cells. Furthermore, cells
      from 28-month-old mice were more sensitive to TNF-alpha-induced RANTES and VCAM-1
      up-regulation. The effect of TNF-alpha on RANTES expression was mediated by TNF
      receptor 1. Interestingly, mesangial cells isolated from 28-month-old mice had
      increased nuclear factor-kappaB transcriptional activity. Inhibition of nuclear
      factor-kappaB activity decreased baseline as well as TNF-alpha-induced RANTES and
      VCAM-1 expression in mesangial cells isolated from 28-month-old mice. Thus,
      phenotypic changes in mesangial cells may predispose them to inflammatory
      stimuli, such as TNF-alpha, which would contribute to glomerular macrophage
      infiltration and inflammatory lesions in aging.

PMID- 15509548
TI  - Quantitative gene expression profiling in formalin-fixed, paraffin-embedded
      tissues using universal bead arrays.
AB  - We recently developed a sensitive and flexible gene expression profiling system
      that is not dependent on an intact poly-A tail and showed that it could be used
      to analyze degraded RNA samples. We hypothesized that the DASL (cDNA-mediated
      annealing, selection, extension and ligation) assay might be suitable for the
      analysis of formalin-fixed, paraffin-embedded tissues, an important source of
      archival tissue material. We now show that, using the DASL assay system, highly
      reproducible tissue- and cancer-specific gene expression profiles can be obtained
      with as little as 50 ng of total RNA isolated from formalin-fixed tissues that
      had been stored from 1 to over 10 years. Further, tissue- and cancer-specific
      markers derived from previous genome-wide expression profiling studies of fresh
      frozen samples were validated in the formalin-fixed samples. The DASL assay
      system should prove useful for high-throughput expression profiling of archived
      clinical samples.

PMID- 15509549
TI  - Synaptic changes in Alzheimer's disease: increased amyloid-beta and gliosis in
      surviving terminals is accompanied by decreased PSD-95 fluorescence.
AB  - In an effort to examine changes that precede synapse loss, we have measured
      amyloid-beta and a series of damage markers in the synaptic compartment of
      Alzheimer's disease (AD) cases. Because localization of events to the terminal
      region in neurons is problematic with conventional methods, we prepared
      synaptosomes from samples of cryopreserved human association cortex, and
      immunolabeled terminals with a procedure for intracellular antigens. Fluorescence
      was quantified using flow cytometry. The viability dye calcein AM was unchanged
      in AD terminals compared to controls, and the fraction of large synaptosome
      particles did not change, although a striking loss of large terminals was
      observed in some AD cases. The percent positive fraction for a series of pre- and
      postsynaptic markers was not affected by AD in this cohort. However, the amyloid
      beta-positive fraction increased from 16 to 27% (P < 0.02) in terminals from AD
      cortex. The expression level on a per-terminal basis is indicated in this assay
      by fluorescence (relative fluorescence units). The fluorescence of presynaptic
      markers did not change in AD terminals, but PSD-95 fluorescence was decreased by
      19% (P < 0.03). Amyloid-beta fluorescence was increased by 132% (P < 0.01), and
      glial fibrillary acidic protein labeling by 31% (P < 0.01). These results suggest
      that synapse-associated amyloid-beta is prominent in regions relatively
      unaffected by AD lesions, and that amyloid accumulation in surviving terminals is
      accompanied by gliosis and alteration in the postsynaptic structure.

PMID- 15509550
TI  - The role of interleukin-1beta in direct and toll-like receptor 4-mediated
      neutrophil activation and survival.
AB  - The regulation of systemic and local neutrophil activation is crucial to the
      clearance of infections and the successful resolution of inflammation without
      progress to tissue damage or disseminated inflammatory reactions. Using purified
      lipopolysaccharide (pLPS) and highly purified neutrophils, we have previously
      shown that Toll-like receptor 4 signaling is a potent neutrophil activator, but a
      poor stimulator of survival. In the presence of peripheral blood mononuclear
      cells (PBMCs), however, pLPS becomes a potent neutrophil survival factor.
      Interleukin (IL)-1beta has been identified as an important neutrophil activator
      and prosurvival cytokine, and is produced in abundance by LPS-stimulated PBMCs.
      We now show that IL-1beta fails to activate highly purified neutrophils or
      enhance their survival, but in the presence of PBMCs, IL-1beta induces neutrophil
      survival. We hypothesized that LPS-primed neutrophils might become responsive to
      IL-1beta, but were unable to demonstrate this. Moreover, IL-1ra failed to prevent
      pLPS + PBMC-dependent neutrophil survival. In studies of IL-1R1(-/-) mice, we
      found that LPS was still able to mediate neutrophil survival, and neutrophil
      survival was enhanced by the addition of monocytic cells. Thus an important
      paradigm of neutrophil regulation needs to be viewed in the context of a cellular
      network in which actions of IL-1beta on neutrophils are indirect and mediated by
      other cells.

PMID- 15509551
TI  - Reversible demyelination, blood-brain barrier breakdown, and pronounced
      neutrophil recruitment induced by chronic IL-1 expression in the brain.
AB  - Interleukin-1beta (IL-1) expression is associated with a spectrum of
      neuroinflammatory processes related to chronic neurodegenerative diseases. The
      single-bolus microinjection of IL-1 into the central nervous system (CNS)
      parenchyma gives rise to delayed and localized neutrophil recruitment, transient
      blood-brain barrier (BBB) breakdown, but no overt damage to CNS integrity.
      However, acute microinjections of IL-1 do not mimic the chronic IL-1 expression,
      which is a feature of many CNS diseases. To investigate the response of the CNS
      to chronic IL-1 expression, we injected a recombinant adenovirus expressing IL-1
      into the striatum. At the peak of IL-1 expression (days 8 and 14 post-injection),
      there was a marked recruitment of neutrophils, vasodilatation, and breakdown of
      the BBB. Microglia and astrocyte activation was evident during the first 14 days
      post-injection. At days 8 and 14, extensive demyelination was observed but the
      number of neurons was not affected by any treatment. Finally, at 30 days, signs
      of inflammation were no longer present, there was evidence of tissue
      reorganization, the BBB was intact, and the process of remyelination was
      noticeable. In summary, our data show that chronic expression of IL-1, in
      contrast to its acute delivery, can reversibly damage CNS integrity and
      implicates this cytokine or downstream components as major mediators of
      demyelination in chronic inflammatory and demyelinating diseases.

PMID- 15509552
TI  - Prion replication alters the distribution of synaptophysin and caveolin 1 in
      neuronal lipid rafts.
AB  - The main event in the pathogenesis of prion diseases is the conversion of the
      cellular prion protein (PrP(C)) into the abnormal, protease-resistant prion
      protein (PrP(res)). PrP(C) is a GPI-anchored protein located in lipid rafts or
      detergent-resistant membranes (DRMs). Here we describe the association of PrP
      with DRMs in neuronal cell bodies and axons during the course of murine scrapie
      and its relation with the distribution of the PrP-interacting proteins caveolin 1
      and synaptophysin. Scrapie infection triggered the accumulation of PrP(res) in
      DRMs from retinas and optic nerves from early stages of the disease before
      evidence of neuronal cell loss. Most of the PrP(res) remained associated with
      lipid rafts throughout different stages in disease progression. In contrast to
      PrP(res), caveolin 1 and synaptophysin in retina and optic nerves shifted to non
      DRM fractions during the course of scrapie infection. The accumulation of
      PrP(res) in DRMs was not associated with a general alteration in their
      composition, because no change in the total protein distribution across the
      sucrose gradient or in the flotation characteristics of the glycosphingolipid GM1
      or Thy-1 were observed until advanced stages of the disease. However, an increase
      in total cholesterol levels was observed in optic nerve and retinas. Only during
      late stages of the disease was a decrease in the number of neuronal cell bodies
      observed, suggesting that synaptic abnormalities are the earliest sign of
      neuronal dysfunction that ultimately results in neuronal death. These results
      indicate that prion replication triggers an abnormal localization of caveolin 1
      and synaptophysin, which in turn may alter neuronal function.

PMID- 15509553
TI  - Involvement of endoplasmic reticulum stress in insulin resistance and diabetes.
AB  - Type 2 diabetes is one of the most prevalent and serious metabolic diseases in
      the world, and insulin resistance and pancreatic beta-cell dysfunction are the
      hallmarks of the disease. In this study, we have shown that endoplasmic reticulum
      (ER) stress, which is provoked under diabetic conditions, plays a crucial role in
      the insulin resistance found in diabetes by modifying the expression of oxygen
      regulated protein 150 (ORP150), a molecular chaperone that protects cells from ER
      stress. Sense ORP overexpression in the liver of obese diabetic mice
      significantly improved insulin resistance and markedly ameliorated glucose
      tolerance. Conversely, expression of antisense ORP150 in the liver of normal mice
      decreased insulin sensitivity. The phosphorylation state of IRS-1 and Akt, which
      are key molecules for insulin signaling, and the expression levels of
      phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, key enzymes of
      gluconeogenesis, were also altered by ORP150 overexpression. This is the first
      report showing that ER stress plays a crucial role in the insulin resistance
      found in diabetes and thus could be a potential therapeutic target for diabetes.

PMID- 15509554
TI  - Inhibition of glucocorticoid-induced apoptosis by targeting the major splice
      variants of BIM mRNA with small interfering RNA and short hairpin RNA.
AB  - Glucocorticoids (GCs) induce apoptosis in lymphocytes and are effective agents
      for the treatment of leukemia. The activated glucocorticoid receptor initiates a
      transcriptional program leading to caspase activation and cell death, but the
      critical signaling intermediates in GC-induced apoptosis remain largely
      undefined. We have observed that GC induction of the three major protein products
      of the Bcl-2 relative Bim (BimEL, BimS, and BimL) correlates with GC sensitivity
      in a panel of human precursor B-cell (pre-B) acute lymphoblastic leukemia (ALL)
      cell lines. To test the hypothesis that Bim facilitates GC-induced apoptosis, we
      reduced BIM mRNA levels and Bim protein levels by RNA interference in highly GC
      sensitive pre-B ALL cells. Reducing Bim proteins by either electroporation of
      synthetic small interfering RNA (siRNA) duplexes or lentivirus-mediated stable
      expression of short hairpin RNA inhibited the activation of caspase-3 and
      increased cell viability following GC exposure. We also observed that the extent
      of GC resistance correlated with siRNA silencing potency. siRNA duplexes that
      reduced only BimEL or BimEL and BimL (but not BimS) exhibited less GC resistance
      than a potent siRNA that silenced all three major isoforms, implying that
      induction of all three Bim proteins contributes to cell death. Finally, the
      modulation of GC-induced apoptosis caused by Bim silencing was independent of Bcl
      2 expression levels, negating the hypothesis that the ratio of Bim to Bcl-2
      regulates apoptosis. These results offer evidence that the induction of Bim by GC
      is a required event for the complete apoptotic response in pre-B ALL cells.

PMID- 15509555
TI  - p53 suppresses c-Myb-induced trans-activation and transformation by recruiting
      the corepressor mSin3A.
AB  - p53 is known to repress transcription of a number of genes, but the mechanism of
      p53 recruitment to these target genes is unknown. The c-myb proto-oncogene
      product (c-Myb) positively regulates proliferation of immature hematopoietic
      cells, whereas p53 blocks cell cycle progression. Here, we demonstrate that p53
      inhibits c-Myb-induced transcription and transformation by directly binding to c
      Myb. The ability of c-Myb to maintain the undifferentiated state of M1 cells was
      also suppressed by p53. p53 did not affect the ability of c-Myb to bind to DNA
      but formed a ternary complex with the corepressor mSin3A and c-Myb. Thus, p53
      antagonizes c-Myb by recruiting mSin3A to down-regulate specific Myb target
      genes.

PMID- 15509556
TI  - Characterization of a novel type of endogenous activator of soluble guanylyl
      cyclase.
AB  - Nitric oxide (NO) remains the only firmly established endogenous modulator of
      soluble guanylyl cyclase (sGC) activity, but physiological, structural, and
      biochemical evidence now suggests that in vivo regulation of sGC involves direct
      interaction with other factors. We searched for such endogenous modulators in
      human umbilical vein endothelial cells and COS-7 cells. The cytosolic fraction of
      both cell types stimulated the activity of semipurified sGC severalfold in the
      absence or presence of a saturating concentration of NO. The cytosolic factor was
      sensitive to proteinase K and destroyed by boiling, suggesting that it contains a
      protein component. Size exclusion chromatography revealed peaks of activity
      between 40 and 70 kDa. The sGC-activating effect was further purified by ion
      exchange chromatography. In the presence of the benzylindazole YC-1 or NO, the
      partially purified factor synergistically activated sGC, suggesting that this
      factor had a mode of activation different from that of YC-1 or NO. Four candidate
      activators were identified from the final purification step by matrix-assisted
      laser desorption ionization mass spectrometry analysis. Using an sGC affinity
      matrix, one of them, the molecular chaperone Hsp70, was shown to directly
      interact with sGC. This interaction was further confirmed by co
      immunoprecipitation in lung tissues and by co-localization in smooth muscle
      cells. sGC and Hsp70 co-localized at the plasma membrane, supporting the idea
      that sGC can be translocated to the membrane. Hsp70 co-purifies with the sGC
      activating effect, and immunodepletion of Hsp70 from COS-7 cytosol coincided with
      a marked attenuation of the sGC-activating effect, yet the effect was not rescued
      by the addition of pure Hsp70. Thus, Hsp70 is a novel sGC-interacting protein
      that is responsible for the sGC-activating effect, probably in association with
      other factors or after covalent modification.

PMID- 15509557
TI  - Drosophila fear of intimacy encodes a Zrt/IRT-like protein (ZIP) family zinc
      transporter functionally related to mammalian ZIP proteins.
AB  - Zinc is essential for many cellular processes, and its concentration in the cell
      must be tightly controlled. The Zrt/IRT-like protein (ZIP) family of zinc
      transporters have recently been identified as the main regulators of zinc influx
      into the cytoplasm; however, little is known about their in vivo roles.
      Previously, we have shown that fear of intimacy (foi) encodes a putative member
      of the ZIP family that is essential for development in Drosophila. Here we
      demonstrate that FOI can act as an ion transporter in both yeast and mammalian
      cell assays and is specific for zinc. We also provide insight into the mechanism
      of action of the ZIP family through membrane topology and structure-function
      analyses of FOI. Our work demonstrates that Drosophila FOI is closely related to
      mammalian ZIP proteins at the functional level and that Drosophila represents an
      ideal system for understanding the in vivo roles of this family. In addition,
      this work indicates that the control of zinc by ZIP transporters may play a
      critical role in regulating developmental processes.

PMID- 15509558
TI  - Processive methylation of hemimethylated CpG sites by mouse Dnmt1 DNA
      methyltransferase.
AB  - DNA methyltransferase Dnmt1 ensures clonal transmission of lineage-specific DNA
      methylation patterns in a mammalian genome during replication. Dnmt1 is targeted
      to replication foci, interacts with PCNA, and favors methylating the
      hemimethylated form of CpG sites. To understand the underlying mechanism of its
      maintenance function, we purified recombinant forms of full-length Dnmt1, a
      truncated form of Dnmt1-(291-1620) lacking the binding sites for PCNA and DNA and
      examined their processivity using a series of long unmethylated and
      hemimethylated DNA substrates. Direct analysis of methylation patterns using
      bisulfite-sequencing and hairpin-PCR techniques demonstrated that full-length
      Dnmt1 methylates hemimethylated DNA with high processivity and a fidelity of over
      95%, but unmethylated DNA with much less processivity. The truncated form of
      Dnmt1 showed identical properties to full-length Dnmt1 indicating that the N
      terminal 290-amino acid residue region of Dnmt1 is not required for preferential
      activity toward hemimethylated sites or for processivity of the enzyme.
      Remarkably, our analyses also revealed that Dnmt1 methylates hemimethylated CpG
      sites on one strand of double-stranded DNA during a single processive run. Our
      findings suggest that these inherent enzymatic properties of Dnmt1 play an
      essential role in the faithful and efficient maintenance of methylation patterns
      in the mammalian genome.

PMID- 15509559
TI  - Use of photoaffinity labeling and site-directed mutagenesis for identification of
      the key residue responsible for extraordinarily high affinity binding of UCN-01
      in human alpha1-acid glycoprotein.
AB  - 7-Hydroxystaurosporine (UCN-01) is a protein kinase inhibitor anticancer drug
      currently undergoing a phase II clinical trial. The low distribution volumes and
      systemic clearance of UCN-01 in human patients have been found to be caused in
      part by its extraordinarily high affinity binding to human alpha1-acid
      glycoprotein (hAGP). In the present study, we photolabeled hAGP with [3H]UCN-01
      without further chemical modification. The photolabeling specificity of [3H]UCN
      01 was confirmed by findings in which other hAGP binding ligands inhibited
      formation of covalent bonds between hAGP and [3H]UCN-01. The amino acid sequence
      of the photolabeled peptide was concluded to be SDVVYTDXK, corresponding to
      residues Ser-153 to Lys-161 of hAGP. No PTH derivatives were detected at the 8th
      cycle, which corresponded to the 160th Trp residue. This strongly implies that
      Trp-160 was photolabeled by [3H]UCN-01. Three recombinant hAGP mutants (W25A,
      W122A, and W160A) and wild-type recombinant hAGP were photolabeled by [3H]UCN-01.
      Only mutant W160A showed a marked decrease in the extent of photoincorporation.
      These results strongly suggest that Trp-160 plays a prominent role in the high
      affinity binding of [3H]UCN-01 to hAGP. A docking model of UCN-01 and hAGP around
      Trp-160 provided further details of the binding site topology.

PMID- 15509560
TI  - Trypanosoma brucei glycoproteins contain novel giant poly-N-acetyllactosamine
      carbohydrate chains.
AB  - The flagellar pocket of the bloodstream form of the African sleeping sickness
      parasite Trypanosoma brucei contains material that binds the beta-d-galactose
      specific lectin ricin (Brickman, M. J., and Balber, A. E. (1990) J. Protozool.
      37, 219-224). Glycoproteins were solubilized from bloodstream form T. brucei
      cells in 8 M urea and 3% SDS and purified by ricin affinity chromatography.
      Essentially all binding of ricin to these glycoproteins was abrogated by
      treatment with peptide N-glycosidase, showing that the ricin ligands are attached
      to glycoproteins via N-glycosidic linkages to asparagine residues. Glycans
      released by peptide N-glycosidase were resolved by Bio-Gel P-4 gel filtration
      into two fractions: a low molecular mass mannose-rich fraction and a high
      molecular mass galactose and N-acetylglucosamine-rich fraction. The latter
      fraction was further separated by high pH anion exchange chromatography and
      analyzed by gas chromatography mass spectrometry, one- and two-dimensional NMR,
      electrospray mass spectrometry, and methylation linkage analysis. The high
      molecular mass ricin-binding N-glycans are based on a conventional Manalpha1
      3(Manalpha1-6)Manbeta1-4-GlcNAcbeta1-4GlcNAc core structure and contain poly-N
      acetyllactosamine chains. A significant proportion of these structures are
      extremely large and of unusual structure. They contain an average of 54 N
      acetyllactosamine (Galbeta1-4GlcNAc) repeats per glycan, linked mostly by 
      4GlcNAcbeta1-6Galbeta1-interrepeat linkages, with an average of one -4GlcNAcbeta1
      3(-4GlcNAcbeta1-6)Galbeta1- branch point in every six repeats. These structures,
      which also bind tomato lectin, are twice the size reported for the largest
      mammalian poly-N-acetyllactosamine N-linked glycans and also differ in their
      preponderance of -4GlcNAcbeta1-6Galbeta1- over -4GlcNacbeta1-3Galbeta1-
      interrepeat linkages. Molecular modeling suggests that -4GlcNAcbeta1-6Galbeta1-
      interrepeat linkages produce relatively compact structures that may give these
      giant N-linked glycans unique physicochemical properties. Fluorescence microscopy
      using fluorescein isothiocyanatericin indicates that ricin ligands are located
      mainly in the flagellar pocket and in the endosomal/lysosomal system of the
      trypanosome.

PMID- 15509561
TI  - UDP-glucuronic acid:anthocyanin glucuronosyltransferase from red daisy (Bellis
      perennis) flowers. Enzymology and phylogenetics of a novel
      glucuronosyltransferase involved in flower pigment biosynthesis.
AB  - In contrast to the wealth of biochemical and genetic information on vertebrate
      glucuronosyltransferases (UGATs), only limited information is available on the
      role and phylogenetics of plant UGATs. Here we report on the purification,
      characterization, and cDNA cloning of a novel UGAT involved in the biosynthesis
      of flower pigments in the red daisy (Bellis perennis). The purified enzyme,
      BpUGAT, was a soluble monomeric enzyme with a molecular mass of 54 kDa and
      catalyzed the regiospecific transfer of a glucuronosyl unit from UDP-glucuronate
      to the 2''-hydroxyl group of the 3-glucosyl moiety of cyanidin 3-O-6''-O
      malonylglucoside with a kcat value of 34 s(-1) at pH 7.0 and 30 degrees C. BpUGAT
      was highlyspecific for cyanidin 3-O-glucosides (e.g. Km for cyanidin 3-O-6''-O
      malonylglucoside, 19 microM) and UDP-glucuronate (Km, 476 microM). The BpUGAT
      cDNA was isolated on the basis of the amino acid sequence of the purified enzyme.
      Quantitative PCR analysis showed that transcripts of BpUGAT could be specifically
      detected in red petals, consistent with the temporal and spatial distributions of
      enzyme activity in the plant and also consistent with the role of the enzyme in
      pigment biosynthesis. A sequence analysis revealed that BpUGAT is related to the
      glycosyltransferase 1 (GT1) family of the glycosyltransferase superfamily
      (according to the Carbohydrate-Active Enzymes (CAZy) data base). Among GT1 family
      members that encompass vertebrate UGATs and plant secondary product
      glycosyltransferases, the highest sequence similarity was found with flavonoid
      rhamnosyltransferases of plants (28-40% identity). Although the biological role
      (pigment biosynthesis) and enzymatic properties of BpUGAT are significantly
      different from those of vertebrate UGATs, both of these UGATs share a similarity
      in that the products produced by these enzymes are more water-soluble, thus
      facilitating their accumulation in vacuoles (in BpUGAT) or their excretion from
      cells (in vertebrate UGATs), corroborating the proposed general significance of
      GT1 family members in the metabolism of small lipophilic molecules.

PMID- 15509562
TI  - Ser1928 is a common site for Cav1.2 phosphorylation by protein kinase C isoforms.
AB  - Voltage-dependent Ca(2+) channel (Ca(v)1.2, L-type Ca(2+) channel) function is
      highly regulated by hormones and neurotransmitters in large part through the
      activation of kinases and phosphatases. Regulation of Ca(v)1.2 by protein kinase
      C (PKC) is of significant physiologic importance, mediating, in part, the cardiac
      response to hormonal regulation. Although PKC has been reported to mediate
      activation and/or inhibition of Ca(v)1.2 function, the molecular mechanisms
      mediating the response have not been definitively elucidated. We show that PKC
      forms a macromolecular complex with the alpha(1c) subunit of Ca(v)1.2 through
      direct interaction with the C terminus. This interaction leads to phosphorylation
      of the channel in response to activators of PKC. We identify Ser(1928) as the
      residue that is phosphorylated by PKC in vitro and in vivo. Ser(1928) has been
      identified previously as the site mediating, in part, the protein kinase A up
      regulation of channel activity. Thus, the protein kinase A and PKC signaling
      pathways converge on the Ca(v)1.2 complex at Ser(1928) to increase channel
      activity. Our results identify two mechanisms leading to regulation of Ca(v)1.2
      activity by PKC: pre-association of the channel with PKC isoforms and
      phosphorylation of specific sites within the alpha(1c) subunit.

PMID- 15509563
TI  - The ATP paradox is the expression of an economizing fuel mechanism.
AB  - The strong negative correlation between glycolytic flux and intracellular ATP
      concentration observed in yeast has long been an intriguing and counterintuitive
      phenomenon, which has been referred to as the ATP paradox. Herein, using
      principles of irreversible thermodynamics it was shown that if the ATP-consuming
      pathways are more sensitive to extracellular glucose than glycolysis, then upon
      glucose addition glycolysis performance can switch from an efficient working
      regime to a dissipative regime, and vice versa, depending on glucose
      availability. The efficient regime represents a good compromise between high
      output power and low dissipation, whereas the dissipative working regime offers a
      higher output power although at a high glucose cost. The physiological and
      evolutionary implications of this switch strategy are discussed.

PMID- 15509564
TI  - Identification of human VPS37C, a component of endosomal sorting complex required
      for transport-I important for viral budding.
AB  - Endosomal sorting complex required for transport-I (ESCRT-I) is one of three
      defined protein complexes in the class E vacuolar protein sorting (VPS) pathway
      required for the sorting of ubiquitinated transmembrane proteins into internal
      vesicles of multivesicular bodies. In yeast, ESCRT-I is composed of three
      proteins, VSP23, VPS28, and VPS37, whereas in mammals only Tsg101(VPS23) and
      VPS28 were originally identified as ESCRT-I components. Using yeast two-hybrid
      screens, we identified one of a family of human proteins (VPS37C) as a Tsg101
      binding protein. VPS37C can form a ternary complex with Tsg101 and VPS28 by
      binding to a domain situated toward the carboxyl terminus of Tsg101 and binds to
      another class E VPS factor, namely Hrs. In addition, VPS37C is recruited to
      aberrant endosomes induced by overexpression of Tsg101, Hrs, or dominant negative
      form of the class E VPS ATPase, VPS4. Enveloped viruses that encode PTAP motifs
      to facilitate budding exploit ESCRT-I as an interface with the class E VPS
      pathway, and accordingly, VPS37C is recruited to the plasma membrane along with
      Tsg101 by human immunodeficiency virus, type 1 (HIV-1) Gag. Moreover, direct
      fusion of VPS37C to HIV-1 Gag obviates the requirement for a PTAP motif to induce
      virion release. Depletion of VPS37C from cells does not inhibit murine leukemia
      virus budding, which is not mediated by ESCRT-I, however, if murine leukemia
      virus budding is engineered to be ESCRT-I-dependent, then it is inhibited by
      VPS37C depletion, and this inhibition is accentuated if VPS37B is simultaneously
      depleted. Thus, this study identifies VPS37C as a functional component of
      mammalian ESCRT-I.

PMID- 15509565
TI  - Changed conformation of mutant Tau-P301L underlies the moribund tauopathy, absent
      in progressive, nonlethal axonopathy of Tau-4R/2N transgenic mice.
AB  - Protein tau-3R/4R isoform ratio and phosphorylation regulates binding to
      microtubules and, when disturbed by aging or mutations, results in diverse
      tauopathies and in neurodegeneration. The underlying mechanisms were studied here
      in three transgenic mouse strains with identical genetic background, all
      expressing the tau-4R/2N isoform driven specifically in neurons by the thy1 gene
      promoter. Two strains, expressing human tau-4R/2N or mutant tau-4R/2N-P301L at
      similar, moderate levels, developed very different phenotypes. Tau-4R/2N mice
      became motor-impaired already around age 6-8 weeks, accompanied by axonopathy
      (dilatations, spheroids), but no tau aggregates, and surviving normally. In
      contrast, tau-P301L mice developed neurofibrillary tangles from age 6 months,
      without axonal dilatations and, despite only minor motor problems, all succumbing
      before the age of 13 months. The third strain, obtained by tau knock-out/knock-in
      (tau-KOKI), expressed normal levels of wild-type human tau-4R/2N replacing all
      mouse tau isoforms. Tau-KOKI mice survived normally with minor motor problems
      late in life and without any obvious pathology. Biochemically, a fraction of
      neuronal tau in aging tau-P301L mice was hyperphosphorylated concomitant with
      conformational changes and aggregation, but overall, tau-4R/2N was actually more
      phosphorylated than tau-P301L. Significantly, tau with changed conformation and
      with hyperphosphorylation colocalized in the same neurons in aging tau-P301L
      mice. Taken together, we conclude that excessive binding of tau-4R/2N as opposed
      to reduced binding of tau-P301L to microtubules is responsible for the
      development of axonopathy and tauopathy, respectively, in tau-4R/2N and tau-P301L
      mice and that the conformational change of tau-P301L is a major determinant in
      triggering the tauopathy.

PMID- 15509566
TI  - Amphiregulin is a novel growth factor involved in normal bone development and in
      the cellular response to parathyroid hormone stimulation.
AB  - Parathyroid hormone (PTH) is the major mediator of calcium homeostasis and bone
      remodeling and is now known to be an effective drug for osteoporosis treatment.
      Yet the mechanisms responsible for its functions in bone are largely unknown.
      Here we report that the expression of amphiregulin (AR), a member of the
      epidermal growth factor (EGF) family, is rapidly and highly up-regulated by PTH
      in several osteoblastic cell lines and bone tissues. Other osteotropic hormones
      (1alpha,25-dihydroxyvitamin D3 and prostaglandin E2) also strongly stimulate AR
      expression. We found all EGF-like ligands and their receptors are expressed in
      osteoblasts, but AR is the only member that is highly regulated by PTH.
      Functional studies demonstrated that although AR is a potent growth factor for
      preosteoblasts, it completely inhibits further differentiation. AR also strongly
      and quickly stimulated Akt and ERK phosphorylation and c-fos and c-jun expression
      in an EGF receptor-dependent manner. Moreover, AR null mice displayed
      significantly less tibial trabecular bone than wild-type mice. Taken together, we
      have identified a novel growth factor that is PTH-regulated and appears to have
      an important role in bone metabolism.

PMID- 15509567
TI  - Rapid and transient activation of transcription of the ERF3 gene by wounding in
      tobacco leaves: possible involvement of NtWRKYs and autorepression.
AB  - This study investigated the regulatory mechanism of rapid and transient induction
      of a transcriptional repressor ERF3 gene by wounding in tobacco (Nicotiana
      tabacum) leaves. Deletion and mutation analysis of the promoter region have
      suggested that the proximal W boxes (TGAC(C/T)) and a GCC box, respectively, may
      be involved in the positive and negative regulation of wound-induced expression
      of the ERF3 gene. Electrophoretic mobility shift assays indicated that wounding
      enhanced the specific binding activity of nuclear factors to the W boxes.
      NtWRKY1, -2, and -4, which are tobacco group I WRKYs, interacted specifically
      with the W boxes and activated transcription via the W boxes. On the other hand,
      deletion of the GCC box from NsERF3 promoter-GUS reporter gene caused a delay in
      down-regulation of transcription after wound induction. In addition, ERF3
      repressed transcription via the NsERF3 promoter activated by NtWRKYs. These
      results suggest the possible involvement of NtWRKYs and autorepression in the
      rapid and transient expression of the ERF3 gene by wounding.

PMID- 15509568
TI  - Differential regulation of Rad18 through Rad6-dependent mono- and
      polyubiquitination.
AB  - Rad18 is involved in postreplication repair mainly through monoubiquitination of
      proliferating cell nuclear antigen (PCNA). Here we show that Rad18 protein was
      detected in human cells as two major bands at 75 and 85 kDa by Western blot. The
      bands were identified as nonubiquitinated and monoubiquitinated forms of Rad18,
      respectively, by mass spectrometry. Multiple ubiquitinated bands of Rad18 were
      detected in vitro in the presence of E1, E2 (Rad6), and methylated ubiquitin,
      indicating that Rad18 was monoubiquitinated at multiple sites through
      autoubiquitination. Rad18 self-associates, and this interaction was abolished by
      replacing one of the conserved cysteine residues with phenylalanine in the zinc
      finger domain (C207F). In the C207F mutant Rad18, monoubiquitination of Rad18 was
      not observed in vivo, suggesting that self-association was critical for
      monoubiquitination. Monoubiquitinated Rad18 was detected mainly in the cytoplasm,
      whereas nonubiquitinated Rad18 was detected predominantly in the nuclei.
      Furthermore, Rad18 was shown to be polyubiquitinated in cells treated with
      proteasome inhibitors. Purified Rad18 was also polyubiquitinated in an in vitro
      system containing E1, E2 (Rad6), and ubiquitin, and it was degraded by the
      addition of proteasomes. These results suggest that the amount of Rad18 in the
      nucleus is regulated differentially by mono- and polyubiquitination.

PMID- 15509569
TI  - Overlap of interaction domains indicates a central role of the P protein in
      assembly and regulation of the Borna disease virus polymerase complex.
AB  - The active polymerase complex of Borna disease virus is composed of the viral
      proteins N, P, and L. The viral X (negative regulatory factor) protein acts as a
      regulator of polymerase activity. Interactions of P with N and X were previously
      studied, but interactions with L were poorly defined. Using a mammalian two
      hybrid system, we observed that L specifically interacts with P but not with N,
      X, or itself. Mapping of the L-binding domain in the P molecule revealed that it
      overlaps with two adjacent domains required for multimerization and interaction
      with N. Competition experiments showed that the interaction between L and P was
      inefficient when N was present, indicating that L may preferentially interact
      with free P in infected cells. Interestingly, a multimerization-defective P
      mutant maintained the ability to interact with L, N, and X but failed to support
      reporter gene expression from an artificial Borna disease virus minigenome.
      Furthermore, dominant negative effects on minigenome activity were only observed
      when P mutants with an intact multimerization domain were used, suggesting that P
      multimers, rather than monomers, exhibit biological activity. P mutants lacking
      functional interaction domains for L or N still formed complexes with these viral
      proteins when wild-type P was available as a bridging molecule, indicating that P
      multimers have the potential to act as scaffolds on which the RNA polymerase
      complex is assembled.

PMID- 15509570
TI  - A single bifunctional UDP-GlcNAc/Glc 4-epimerase supports the synthesis of three
      cell surface glycoconjugates in Campylobacter jejuni.
AB  - The major cell-surface carbohydrates (lipooligosaccharide, capsule, and
      glycoprotein N-linked heptasaccharide) of Campylobacter jejuni NCTC 11168 contain
      Gal and/or GalNAc residues. GalE is the sole annotated UDP-glucose 4-epimerase in
      this bacterium. The presence of GalNAc residues in these carbohydrates suggested
      that GalE might be a UDP-GlcNAc 4-epimerase. GalE was shown to epimerize UDP-Glc
      and UDP-GlcNAc in coupled assays with C. jejuni glycosyltransferases and in sugar
      nucleotide epimerization equilibria studies. Thus, GalE possesses UDP-GlcNAc 4
      epimerase activity and was renamed Gne. The Km(app) values of a purified MalE-Gne
      fusion protein for UDP-GlcNAc and UDP-GalNAc are 1087 and 1070 microm, whereas
      those for UDP-Glc and UDP-Gal are 780 and 784 microm. The kcat and kcat/Km(app)
      values were three to four times higher for UDP-GalNAc and UDP-Gal than for UDP
      GlcNAc and UDP-Glc. The comparison of the kinetic parameters of MalE-Gne to those
      of other characterized bacterial UDP-GlcNAc 4-epimerases indicated that Gne is a
      bifunctional UDP-GlcNAc/Glc 4-epimerase. The UDP sugar-binding site of Gne was
      modeled by using the structure of the UDP-GlcNAc 4-epimerase WbpP from
      Pseudomonas aeruginosa. Small differences were noted, and these may explain the
      bifunctional character of the C. jejuni Gne. In a gne mutant of C. jejuni, the
      lipooligosaccharide was shown by capillary electrophoresis-mass spectrometry to
      be truncated by at least five sugars. Furthermore, both the glycoprotein N-linked
      heptasaccharide and capsule were no longer detectable by high resolution magic
      angle spinning NMR. These data indicate that Gne is the enzyme providing Gal and
      GalNAc residues with the synthesis of all three cell-surface carbohydrates in C.
      jejuni NCTC 11168.

PMID- 15509571
TI  - Phospholipase Cbeta2 binds to and inhibits phospholipase Cdelta1.
AB  - Phospholipase Cbeta (PLCbeta) isoforms, which are under the control of Galphaq
      and Gbetagamma subunits, generate Ca2+ signals induced by a broad array of
      extracellular agonists, whereas PLCdelta isoforms depend on a rise in cytosolic
      Ca2+ for their activation. Here we find that PLCbeta2 binds strongly to PLCdelta1
      and inhibits its catalytic activity in vitro and in living cells. In vitro, this
      PLC complex can be disrupted by increasing concentrations of free Gbetagamma
      subunits. Such competition has consequences for signaling, because in HEK293
      cells PLCbeta2 suppresses elevated basal [Ca2+] and inositol phosphates levels
      and the sustained agonist-induced elevation of Ca2+ levels caused by PLCdelta1.
      Also, expression of both PLCs results in a synergistic release of [Ca2+] upon
      stimulation in A10 cells. These results support a model in which PLCbeta2
      suppresses the basal catalytic activity of PLCdelta1, which is relieved by
      binding of Gbetagamma subunits to PLCbeta2 allowing for amplified calcium
      signals.

PMID- 15509572
TI  - The glutamine residue of the conserved GGQ motif in Saccharomyces cerevisiae
      release factor eRF1 is methylated by the product of the YDR140w gene.
AB  - Polypeptide release factors from eubacteria and eukaryotes, although similar in
      function, belong to different protein families. They share one sequence motif, a
      GGQ tripeptide that is vital to release factor (RF) activity in both kingdoms. In
      bacteria, the Gln residue of the motif in RF1 and RF2 is modified to N(5)-methyl
      Gln by the S-adenosyl l-methionine-dependent methyltransferase PrmC and the
      absence of Gln methylation decreases the release activity of Escherichia coli RF2
      in vitro severalfold. We show here that the same modification is made to the GGQ
      motif of Saccharomyces cerevisiae release factor eRF1, the first time that N(5)
      methyl-Gln has been found outside the bacterial kingdom. The product of the
      YDR140w gene is required for the methylation of eRF1 in vivo and for optimal
      yeast cell growth. YDR140w protein has significant homology to PrmC but lacks the
      N-terminal domain thought to be involved in the recognition of the bacterial
      release factors. Overproduced in S. cerevisiae, YDR140w can methylate eRF1 from
      yeast or man in vitro using S-adenosyl l-methionine as methyl donor provided that
      eRF3 and GTP are also present, suggesting that the natural substrate of the
      methyltransferase YDR140w is the ternary complex eRF1.eRF3.GTP.

PMID- 15509573
TI  - Differential regulation of sterol regulatory element-binding protein 1c
      transcriptional activity by insulin and liver X receptor during liver
      development.
AB  - Sterol regulatory element-binding proteins (SREBPs) are transcription factors
      involved in the synthesis of cholesterol and fatty acids. In adults, the isoform
      SREBP-1c is the predominant transcript in the liver of fed animals, and it
      activates triglyceride production from glucose when diet is enriched in
      carbohydrates. Studies have shown that SREBP-1c expression is dependent on
      insulin but also on the availability of oxysterols, ligands of the nuclear liver
      X receptor (LXR). The aim of this study was to investigate the regulation of the
      hepatic SREBP-1c expression in vivo in situations where drastic nutritional and
      hormonal changes occur, from the gestation to the weaning period. In this paper,
      we report the discovery of LXR-independent SREBP-1c transcriptional activity
      during late gestation. In utero insulin injection prior to the natural rise in
      insulin in late gestation triggers SREBP-1c mRNA elevation, nuclear SREBP-1c
      binding activity, and expression of its target genes independently of LXR
      transactivation. On the other hand, during suckling, we observed strong SREBP-1c
      mRNA expression despite very low plasma insulin, an expression that may be due to
      LXR transactivation. In contrast to insulin, LXR is not sufficient to trigger
      nuclear SREBP-1c binding activity and target gene induction. This could be due to
      the concomitant induction of INSIG-2a by LXR and subsequent retention of SREBP-1c
      in the endoplasmic reticulum.

PMID- 15509574
TI  - Suppression of wild-type rhodopsin maturation by mutants linked to autosomal
      dominant retinitis pigmentosa.
AB  - Autosomal dominant retinitis pigmentosa (ADRP) has been linked to mutations in
      the gene encoding rhodopsin. Most RP-linked rhodopsin mutants are unable to fold
      correctly in the endoplasmic reticulum, are degraded by the ubiquitin proteasome
      system, and are highly prone to forming detergent-insoluble high molecular weight
      aggregates. Here we have reported that coexpression of folding-deficient, but not
      folding-proficient, ADRP-linked rhodopsin mutants impairs delivery of the wild
      type protein to the plasma membrane. Fluorescence resonance energy transfer and
      co-precipitation studies revealed that mutant and wild-type rhodopsins form a
      high molecular weight, detergent-insoluble complex in which the two proteins are
      in close (<70 A) proximity. Co-expression of ARDP-linked rhodopsin folding
      deficient mutants resulted in enhanced proteasome-mediated degradation and steady
      state ubiquitination of the wild-type protein. These data suggested a dominant
      negative effect on conformational maturation that may underlie the dominant
      inheritance of ARDP.

PMID- 15509575
TI  - Wnt-3a-dependent cell motility involves RhoA activation and is specifically
      regulated by dishevelled-2.
AB  - Wnts stimulate cell migration, although the mechanisms responsible for this
      effect are not fully understood. To investigate the pathways that mediate Wnt
      dependent cell motility, we treated Chinese hamster ovary cells with Wnt-3a
      conditioned medium and monitored changes in cell shape and movement. Wnt-3a
      induced cell spreading, formation of protrusive structures, reorganization of
      stress fibers and migration. Although Wnt-3a stabilized beta-catenin, two
      inhibitors of the beta-catenin/canonical pathway, Dickkopf-1 and a dominant
      negative T cell factor construct, did not reduce motility. The small GTPase RhoA
      also was activated by Wnt-3a. In contrast to beta-catenin signaling, inhibition
      of Rho kinase partially blocked motility. Because Dishevelled (Dvl) proteins are
      effectors of both canonical and noncanonical Wnt signaling, we used
      immunofluorescent analysis and small interference RNA technology to evaluate the
      role of Dvl in cell motility. Specific knock-down of Dvl-2 expression markedly
      reduced Wnt-3a-dependent changes in cell shape and movement, suggesting that this
      Dvl isoform had a predominant role in mediating Wnt-3a-dependent motility in
      Chinese hamster ovary cells.

PMID- 15509576
TI  - Extended neck regions stabilize tetramers of the receptors DC-SIGN and DC-SIGNR.
AB  - The human cell surface receptors DC-SIGN (dendritic cell-specific intercellular
      adhesion molecule-grabbing nonintegrin) and DC-SIGNR (DC-SIGN-related) bind to
      oligosaccharide ligands found on human tissues as well as on pathogens including
      viruses, bacteria, and parasites. The extracellular portion of each receptor
      contains a membrane-distal carbohydrate-recognition domain (CRD) and forms
      tetramers stabilized by an extended neck region consisting of 23 amino acid
      repeats. Cross-linking analysis of full-length receptors expressed in fibroblasts
      confirms the tetrameric state of the intact receptors. Hydrodynamic studies on
      truncated receptors demonstrate that the portion of the neck of each protein
      adjacent to the CRD is sufficient to mediate the formation of dimers, whereas
      regions near the N terminus are needed to stabilize the tetramers. Some of the
      intervening repeats are missing from polymorphic forms of DC-SIGNR. Two different
      crystal forms of truncated DC-SIGNR comprising two neck repeats and the CRD
      reveal that the CRDs are flexibly linked to the neck, which contains alpha
      helical segments interspersed with non-helical regions. Differential scanning
      calorimetry measurements indicate that the neck and CRDs are independently folded
      domains. Based on the crystal structures and hydrodynamic data, models for the
      full extracellular domains of the receptors have been generated. The observed
      flexibility of the CRDs in the tetramer, combined with previous data on the
      specificity of these receptors, suggests an important role for oligomerization in
      the recognition of endogenous glycans, in particular those present on the
      surfaces of enveloped viruses recognized by these proteins.

PMID- 15509577
TI  - Genetic interactions between BLM and DNA ligase IV in human cells.
AB  - BLM has been implicated in DNA double-strand break (DSB) repair, but its precise
      role remains obscure. To explore this, we generated BLM(-/-) and BLM(-/-)LIG4(-/
      ) cells from the human pre-B cell line Nalm-6. BLM(-/-) cells exhibited retarded
      growth, increased mutation rates, and hypersensitivity to agents that block
      replication fork progression. Interestingly, these phenotypes were significantly
      suppressed by deletion of LIG4, suggesting that nonhomologous end-joining (NHEJ)
      is unfavorable for integrity and survival of cells lacking BLM. We propose that
      the absence of BLM leads to accumulation of replication-associated, one-ended
      DSBs, which are deleterious to cells and lead to genomic instability when
      repaired by NHEJ. In addition, the NHEJ pathway per se was marginally affected by
      BLM deficiency, as evidenced by x-ray sensitivity and I-SceI-based DSB repair
      assays. More intriguingly, however, these experiments revealed the presence of an
      alternative, DNA ligase IV-independent end-joining pathway, which was
      significantly affected by the loss of BLM. Collectively, our results provide the
      first evidence for genetic interactions between BLM and NHEJ in human cells.

PMID- 15509578
TI  - Mutational analysis of TraM correlates oligomerization and DNA binding with
      autoregulation and conjugative DNA transfer.
AB  - F plasmid TraM, an autoregulatory homotetramer, is essential for F plasmid
      bacterial conjugative transfer, one of the major mechanisms for horizontal gene
      dissemination. TraM cooperatively binds to three sites (sbmA, -B, and -C) near
      the origin of transfer in the F plasmid. To examine whether or not
      tetramerization of TraM is required for autoregulation and F conjugation, we used
      a two-plasmid system to screen for autoregulation-defective traM mutants
      generated by random PCR mutagenesis. A total of 72 missense mutations in TraM
      affecting autoregulation were selected, all of which also resulted in a loss of
      TraM function during F conjugation. Mutational analysis of TraM defined three
      regions important for F conjugation, including residues 3-10 (region I), 31-53
      (region II), and 80-121 (region III); in addition, residues 3-47 were also
      important for the immunoreactivity of TraM. Biochemical analysis of mutant
      proteins indicated that region I defined a DNA binding domain that was not
      involved in tetramerization, whereas regions II and III were important for both
      tetramerization and efficient DNA binding. Mutations in region III affected the
      cooperativity of binding of TraM to sbmA, -B, and -C. Our results suggest that
      tetramerization is important for specific DNA binding, which, in turn, is
      essential for traM autoregulation and F conjugation. These findings support the
      hypothesis that TraM functions as a "signaling" factor that triggers DNA
      transport during F conjugation.

PMID- 15509579
TI  - Mitochondria-specific RNA-modifying enzymes responsible for the biosynthesis of
      the wobble base in mitochondrial tRNAs. Implications for the molecular
      pathogenesis of human mitochondrial diseases.
AB  - Human mitochondrial (mt) tRNA(Lys) has a taurine-containing modified uridine, 5
      taurinomethyl-2-thiouridine (taum5s2U), at its anticodon wobble position. We
      previously found that the mt tRNA(Lys), carrying the A8344G mutation from cells
      of patients with myoclonus epilepsy associated with ragged-red fibers (MERRF),
      lacks the taum5s2U modification. Here we describe the identification and
      characterization of a tRNA-modifying enzyme MTU1 (mitochondrial tRNA-specific 2
      thiouridylase 1) that is responsible for the 2-thiolation of the wobble position
      in human and yeast mt tRNAs. Disruption of the yeast MTU1 gene eliminated the 2
      thio modification of mt tRNAs and impaired mitochondrial protein synthesis, which
      led to reduced respiratory activity. Furthermore, when MTO1 or MSS1, which are
      responsible for the C5 substituent of the modified uridine, was disrupted along
      with MTU1, a much more severe reduction in mitochondrial activity was observed.
      Thus, the C5 and 2-thio modifications act synergistically in promoting efficient
      cognate codon decoding. Partial inactivation of MTU1 in HeLa cells by small
      interference RNA also reduced their oxygen consumption and resulted in
      mitochondria with defective membrane potentials, which are similar phenotypic
      features observed in MERRF.

PMID- 15509581
TI  - Cell- and ligand-specific regulation of promoters containing activator protein-1
      and Sp1 sites by estrogen receptors alpha and beta.
AB  - Estrogen plays a critical role in development and maintenance of female
      reproductive and mammary tissues, but is also involved in maintenance of
      cardiovascular, skeletal, and neural function. Although it is widely accepted
      that the estrogen-occupied receptor mediates its effects by interacting with
      estrogen response elements (EREs) residing in target genes, a number of estrogen
      responsive genes contain no identifiable ERE. To understand how estrogen
      responsive genes lacking EREs but containing activator protein 1 (AP-1) and Sp1
      sites respond to hormone treatment, we have identified four discrete regions of
      the human progesterone receptor gene that contain AP-1 or Sp1 sites and examined
      their abilities to modulate transcription in the presence of 17 beta-estradiol,
      ICI 182,780, tamoxifen, raloxifene, genistein, or daidzein. Transient
      cotransfection assays demonstrated that ER alpha was a more potent activator of
      transcription than ER beta in bone, uterine, and mammary cells. The Sp1
      containing promoters were substantially more potent transcriptional enhancers
      than the AP-1-containing promoters, but a 1.5-kb region of the human progesterone
      receptor gene containing both AP-1 and Sp1 sites was the most hormone-responsive
      promoter tested. The ability of ligands to modulate transcription of AP-1- or Sp1
      containing promoters was dependent on cell context, but the expression of AP-1 or
      Sp1 proteins was not necessarily related to transcriptional response. Taken
      together, these studies have helped to delineate the roles of ER alpha and ER
      beta in modulating transcription of genes containing AP-1 and Sp1 sites and
      define the effects of widely used, pharmacologic agents in target cells with
      distinct cellular environments.

PMID- 15509580
TI  - Celastrols as inducers of the heat shock response and cytoprotection.
AB  - Alterations in protein folding and the regulation of conformational states have
      become increasingly important to the functionality of key molecules in signaling,
      cell growth, and cell death. Molecular chaperones, because of their properties in
      protein quality control, afford conformational flexibility to proteins and serve
      to integrate stress-signaling events that influence aging and a range of diseases
      including cancer, cystic fibrosis, amyloidoses, and neurodegenerative diseases.
      We describe here characteristics of celastrol, a quinone methide triterpene and
      an active component from Chinese herbal medicine identified in a screen of
      bioactive small molecules that activates the human heat shock response. From a
      structure/function examination, the celastrol structure is remarkably specific
      and activates heat shock transcription factor 1 (HSF1) with kinetics similar to
      those of heat stress, as determined by the induction of HSF1 DNA binding,
      hyperphosphorylation of HSF1, and expression of chaperone genes. Celastrol can
      activate heat shock gene transcription synergistically with other stresses and
      exhibits cytoprotection against subsequent exposures to other forms of lethal
      cell stress. These results suggest that celastrols exhibit promise as a new class
      of pharmacologically active regulators of the heat shock response.

PMID- 15509582
TI  - Short term cyclin D1 overexpression induces centrosome amplification, mitotic
      spindle abnormalities, and aneuploidy.
AB  - In normal cells, cyclin D1 is induced by growth factors and promotes progression
      through the G(1) phase of the cell cycle. Cyclin D1 is also an oncogene that is
      thought to act primarily by bypassing the requirement for mitogens during the
      G(1) phase. Studies of clinical tumors have found that cyclin D1 overexpression
      is associated with chromosome abnormalities, although a causal effect has not
      been established in experimental systems. In this study, we found that transient
      expression of cyclin D1 in normal hepatocytes in vivo triggered dysplastic
      mitoses, accumulation of supernumerary centrosomes, abnormalities of the mitotic
      spindle, and marked chromosome changes within several days. This was associated
      with up-regulation of checkpoint genes p53 and p21 as well as hepatocyte
      apoptosis in the liver. Transient transfection of cyclin D1 also induced
      centrosome and mitotic spindle abnormalities in breast epithelial cells,
      suggesting that this may be a generalized effect. These results indicate that
      cyclin D1 can induce deregulation of the mitotic apparatus and aneuploidy,
      effects that could contribute to the role of this oncogene in malignancy.

PMID- 15509583
TI  - Modulation of yersinia type three secretion system by the S1 domain of
      polynucleotide phosphorylase.
AB  - Both low temperatures and encounters with host phagocytes are two stresses that
      have been relatively well studied in many species of bacteria. Previous work has
      shown that the exoribonuclease polynucleotide phosphorylase (PNPase) is required
      for Yersiniae to grow at low temperatures. Here, we show that PNPase also
      enhances the ability of Yersinia pseudotuberculosis and Yersinia pestis to
      withstand the killing activities of murine macrophages. PNPase is required for
      the optimal functioning of the Yersinia type three secretion system (TTSS), an
      organelle that injects effector proteins directly into host cells. Unexpectedly,
      the effect of PNPase on the TTSS is independent of its ribonuclease activity and
      instead requires its S1 RNA binding domain. In contrast, catalytically inactive
      enzyme does not enhance the low temperature growth effect of PNPase.
      Surprisingly, wild-type-like TTSS functioning was restored to the pnp mutant
      strain by expressing just the approximately 70 amino acid S1 domains from either
      PNPase, RNase R, RNase II, or RpsA. Our findings suggest that PNPase plays
      multifaceted roles in enhancing Yersinia survival in response to stressful
      conditions.

PMID- 15509584
TI  - Ring1b-mediated H2A ubiquitination associates with inactive X chromosomes and is
      involved in initiation of X inactivation.
AB  - Histone modifications are thought to serve as epigenetic markers that mediate
      dynamic changes in chromatin structure and regulation of gene expression. As a
      model system for understanding epigenetic silencing, X chromosome inactivation
      has been previously linked to a number of histone modifications including
      methylation and hypoacetylation. In this study, we provide evidence that supports
      H2A ubiquitination as a novel epigenetic marker for the inactive X chromosome
      (Xi) and links H2A ubiquitination to initiation of X inactivation. We found that
      the H2A-K119 ubiquitin E3 ligase Ring1b, a Polycomb group protein, is enriched on
      Xi in female trophoblast stem (TS) cells as well as differentiating embryonic
      stem (ES) cells. Consistent with Ring1b mediating H2A ubiquitination,
      ubiquitinated H2A (ubH2A) is also enriched on the Xi of both TS and ES cells. We
      demonstrate that the enrichment of Ring1b and ubH2A on Xi is transient during TS
      and ES cell differentiation, suggesting that the Ring1b and ubH2A are involved in
      the initiation of both imprinted and random X inactivation. Furthermore, we
      showed that the association of Ring1b and ubH2A with Xi is mitotically stable in
      non-differentiated TS cells.

PMID- 15509585
TI  - Anti-oxidative stress system in cyanobacteria. Significance of type II
      peroxiredoxin and the role of 1-Cys peroxiredoxin in Synechocystis sp. strain PCC
      6803.
AB  - Two antioxidant proteins, SLL1621 and SLR1198, were captured in the cyanobacteria
      Synechocystis sp. PCC 6803 using thioredoxin affinity chromatography, which was
      first applied to the survey of thioredoxin target proteins in chloroplasts
      (Motohashi, K., Kondoh, A., Stumpp, M. T., and Hisabori, T. (2001) Proc. Natl.
      Acad. Sci. U. S. A. 98, 11224-11229). They are annotated as AhpC/TSA family
      protein (SLL1621) and antioxidant protein (SLR1198) in CyanoBase (Nakamura, Y.,
      Kaneko, T., Hirosawa, M., Miyajima, N., and Tabata, S. (1998) Nucleic Acids Res.
      26, 63-67). Based on sequence homology analysis SLL1621 and SLR1198 are
      categorized into type II peroxiredoxin and 1-Cys type peroxiredoxin,
      respectively. In vitro interaction between SLL1621 and thioredoxin was confirmed
      using the recombinant proteins expressed in Escherichia coli. Furthermore, we
      found that SLL1621 shows remarkable glutathione-dependent peroxidase activity.
      Disruption of the sll1621 gene had a dramatic effect on the viability of the
      cyanobacterial cells even under weak light conditions (50 micromol.m(-2).s(-1)),
      suggesting this peroxiredoxin is essential for this cyanobacterium. In contrast,
      although the peroxidase activity of SLR1198 was scarcely detected, disruption of
      the gene, slr1198, certainly affected the growth rate of the cells. The results
      indicate the physiological significance of two different peroxiredoxins as an
      anti-oxidative stress system in cyanobacteria.

PMID- 15509586
TI  - Activation of the discoidin domain receptor 2 induces expression of matrix
      metalloproteinase 13 associated with osteoarthritis in mice.
AB  - Human genetic studies indicate that mutations in type IX and XI collagens result
      in early-onset osteoarthritis (OA) with a wide spectrum of osteochondrodysplasia.
      However, a convincing causal chain of events underlying the role of these
      collagen mutations in the pathogenesis of OA has not been elucidated. Here we
      show that the expression of a cell surface collagen receptor, discoidin domain
      receptor 2 (DDR2), is increased in chondrocytes of the articular cartilage of
      knee joints in mice that develop OA as a result of a heterozygous mutation in
      type XI collagen. At the same time point, 6 months, we also found increased
      expression and activity of matrix metalloproteinase 13 (MMP-13) in the mutant
      mouse knee cartilage. The expression of both DDR2 and MMP-13 was increased in
      chondrocytes cultured on plates coated with native type II collagen but not on
      gelatin, and overexpression of DDR2, but not of a truncated form, was found to
      induce the expression of MMP-13 when chondrocytes were cultured on type II
      collagen but not on plastic. The DDR2-induced expression of MMP-13 appears to be
      specific, since we did not observe induction of MMP-1, MMP-3, MMP-8, ADAMTS-4,
      ADAMTS-5, and IL-1 transcripts in human chondrocytes or Mmp-3, Mmp-8, Adamts-4,
      Adamts-5, and Il-1 in mouse chondrocytes. Our data suggest that the defect in the
      cartilage matrix of mice that are heterozygous for a type XI collagen mutation
      (cho/+) permits activation and up-regulation of DDR2 in chondrocytes. This could
      be due to increased exposure of chondrocytes to type II collagen as a result of
      the decreased amount of type XI collagen in the mutant cartilage. The specific
      induction of MMP-13 by DDR2 in response to its cartilage-specific ligand, type II
      collagen, may contribute to cartilage damage in hereditary OA.

PMID- 15509587
TI  - Single amino acid substitutions in procollagen VII affect early stages of
      assembly of anchoring fibrils.
AB  - Procollagen VII is a homotrimer of 350-kDa pro-alpha1(VII) chains, each
      consisting of a central collagenous domain flanked by the noncollagenous N
      terminal NC1 domain and the C-terminal NC2 domain. After secretion from cells,
      procollagen VII molecules form anti-parallel dimers with a C-terminal 60-nm
      overlap. Characteristic alignment of procollagen VII monomers forming a dimer
      depends on site-specific binding between the NC2 domain and the triple-helical
      region adjacent to Cys-2634 of the interacting procollagen VII molecules.
      Formation of the intermolecular disulfide bonds between Cys-2634 and either Cys
      2802 or Cys-2804 is promoted by the cleavage of the NC2 domain by procollagen C
      proteinase. By employing recombinant procollagen VII variants harboring G2575R,
      R2622Q, or G2623C substitutions previously disclosed in patients with dystrophic
      epidermolysis bullosa, we studied how these amino acid substitutions affect
      intermolecular interactions. Binding assays utilizing an optical biosensor
      demonstrated that the G2575R substitution increased affinity between mutant
      molecules. In contrast, homotypic binding between the R2622Q or G2623C molecules
      was not detected. In addition, kinetics of heterotypic binding of all analyzed
      mutants to wild type collagen VII were different from those for binding between
      wild type molecules. Moreover, solid-state binding assays demonstrated that
      R2622Q and G2623C substitutions prevent formation of stable assemblies of
      procollagen C-proteinase-processed mutants. These results indicate that single
      amino acid substitutions in procollagen VII alter its self-assembly and provide a
      basis for understanding the pathomechanisms leading from mutations in the COL7A1
      gene to fragility of the dermal-epidermal junction seen in patients with
      dystrophic forms of epidermolysis bullosa.

PMID- 15509588
TI  - Tumor cell-mediated induction of the stromal factor stromelysin-3 requires
      heterotypic cell contact-dependent activation of specific protein kinase C
      isoforms.
AB  - Stromelysin-3 (ST3, MMP-11) has been shown to be strongly overexpressed in
      stromal fibroblasts of most invasive human carcinomas. However, the molecular
      mechanisms leading to ST3 expression in nonmalignant fibroblasts remain unknown.
      The aim of the present study was to analyze the signaling pathways activated in
      normal pulmonary fibroblasts after their interaction with non-small cell lung
      cancer (NSCLC) cells and leading to ST3 expression. The use of selective
      signaling pathway inhibitors showed that conventional and novel protein kinase Cs
      (PKC) were required for ST3 induction, whereas Src kinases exerted a negative
      control. We observed by both conventional and real time confocal microscopy that
      green fluorescent protein-tagged PKCalpha and PKCepsilon, but not PKCdelta,
      transfected in fibroblasts, accumulate selectively at the cell-cell contacts
      between fibroblasts and tumor cells. In agreement, RNAi-mediated depletion of
      PKCalpha and PKCepsilon, but not PKCdelta significantly decreased co-culture
      dependent ST3 production. Finally, a tetracycline-inducible expression model
      allowed us to confirm the central role of these PKC isoforms and the negative
      regulatory function of c-Src in the control of ST3 expression. Altogether, our
      data emphasize signaling changes occurring in the tumor microenvironment that may
      define new stromal targets for therapeutic intervention.

PMID- 15509589
TI  - Twinkle helicase is essential for mtDNA maintenance and regulates mtDNA copy
      number.
AB  - Mechanisms of mitochondrial DNA (mtDNA) maintenance have recently gained wide
      interest owing to their role in inherited diseases as well as in aging. Twinkle
      is a new mitochondrial 5'-3' DNA helicase, defects of which we have previously
      shown to underlie a mitochondrial disease, progressive external ophthalmoplegia
      with multiple mtDNA deletions. Mouse Twinkle is highly similar to the human
      counterpart, suggesting conserved function. Here, we have characterized the mouse
      Twinkle gene and expression profile and report that the expression patterns are
      not conserved between human and mouse, but are synchronized with the adjacent
      gene MrpL43, suggesting a shared promoter. To elucidate the in vivo role of
      Twinkle in mtDNA maintenance, we generated two transgenic mouse lines
      overexpressing wild-type Twinkle. We could demonstrate for the first time that
      increased expression of Twinkle in muscle and heart increases mtDNA copy number
      up to 3-fold higher than controls, more than any other factor reported to date.
      Additionally, we utilized cultured human cells and observed that reduced
      expression of Twinkle by RNA interference mediated a rapid drop in mtDNA copy
      number, further supporting the in vivo results. These data demonstrate that
      Twinkle helicase is essential for mtDNA maintenance, and that it may be a key
      regulator of mtDNA copy number in mammals.

PMID- 15509590
TI  - PAX4 gene variations predispose to ketosis-prone diabetes.
AB  - Ketosis-prone diabetes (KPD) is a rare form of type 2 diabetes, mostly observed
      in subjects of west African origin (west Africans and African-Americans),
      characterized by fulminant and phasic insulin dependence, but lacking markers of
      autoimmunity observed in type 1 diabetes. PAX4 is a transcription factor
      essential for the development of insulin-producing pancreatic beta-cells.
      Recently, a missense mutation (Arg121Trp) of PAX4 has been implicated in early
      and insulin deficient type 2 diabetes in Japanese subjects. The phenotype
      similarities between KPD and Japanese carriers of Arg121Trp have prompted us to
      investigate the role of PAX4 in KPD. We have screened 101 KPD subjects and we
      have found a new variant in the PAX4 gene (Arg133Trp), specific to the population
      of west African ancestry, and which predisposes to KPD under a recessive model.
      Homozygous Arg133Trp PAX4 carriers were found in 4% of subjects with KPD but not
      in 355 controls or 147 subjects with common type 2 or type 1 diabetes. In vitro,
      the Arg133Trp variant showed a decreased transcriptional repression of target
      gene promoters in an alpha-TC1.6 cell line. In addition, one KPD patient was
      heterozygous for a rare PAX4 variant (Arg37Trp) that was not found in controls
      and that showed a more severe biochemical phenotype than Arg133Trp. Clinical
      investigation of the homozygous Arg133Trp carriers and of the Arg37Trp carrier
      demonstrated a more severe alteration in insulin secretory reserve, during a
      glucagon-stimulation test, compared to other KPD subjects. Together these data
      provide the first evidence that ethnic-specific gene variants may contribute to
      the predisposition to this particular form of diabetes and suggest that KPD, like
      maturity onset diabetes of the young, is a rare, phenotypically defined but
      genetically heterogeneous form of type 2 diabetes.

PMID- 15509591
TI  - Clustering patterns of LOD scores for asthma-related phenotypes revealed by a
      genome-wide screen in 295 French EGEA families.
AB  - A genome-wide scan for asthma phenotypes was conducted in the whole sample of 295
      EGEA families selected through at least one asthmatic subject. In addition to
      asthma, seven phenotypes involved in the main asthma physiopathological pathways
      were considered: SPT (positive skin prick test response to at least one of 11
      allergens), SPTQ score being the number of positive skin test responses to 11
      allergens, Phadiatop (positive specific IgE response to a mixture of allergens),
      total IgE levels, eosinophils, bronchial responsiveness (BR) to methacholine
      challenge and %predicted FEV(1). Four regions showed evidence for linkage
      (P</=0.001): 6q14 for %FEV(1), 12p13 for IgE, 17q22-q24 for SPT and 21q21 for
      both SPTQ and %FEV(1). Nine other regions indicated smaller linkage signals
      (0.001<P</=0.005). While most of these regions have been reported by previous
      asthma and lung function screens, 6q14 appears to be a new region potentially
      linked to %FEV(1). To determine which of these various asthma phenotypes are more
      likely to share common genetic determinants, a principal component analysis was
      applied to the genome-wide LOD scores. This analysis revealed clustering of LODs
      for asthma, SPT and Phadiatop on one axis and clustering of LODs for %FEV(1), BR
      and SPTQ on the other, while LODs for IgE and eosinophils appeared to be
      independent from all other LODs. These results provide new insights into the
      potential sharing of genetic determinants by asthma-related phenotypes.

PMID- 15509592
TI  - A novel mechanism in recessive nephrogenic diabetes insipidus: wild-type
      aquaporin-2 rescues the apical membrane expression of intracellularly retained
      AQP2-P262L.
AB  - Vasopressin regulates water homeostasis through insertion of homotetrameric
      aquaporin-2 (AQP2) water channels in the apical plasma membrane of renal cells.
      AQP2 mutations cause recessive and dominant nephrogenic diabetes insipidus (NDI),
      a disease in which the kidney is unable to concentrate urine in response to
      vasopressin. Until now, all AQP2 mutants in recessive NDI were shown to be
      misfolded, retained in the endoplasmic reticulum (ER) and unable to interact with
      wild-type (wt)-AQP2, whereas AQP2 mutants in dominant NDI are properly folded and
      interact with wt-AQP2, but, due to the mutation, cause missorting of the wt
      AQP2/mutant complex. Here, patients of two families with recessive NDI appeared
      compound heterozygotes for AQP2-A190T or AQP2-R187C mutants, together with AQP2
      P262L. As mutations in the AQP2 C-tail, where P262 resides, usually cause
      dominant NDI, the underlying cell-biological mechanism was investigated. Upon
      expression in oocytes, AQP2-P262L was a properly folded and functional aquaporin
      in contrast to the classical mutants, AQP2-R187C and AQP2-A190T. Expressed in
      polarized cells, AQP2-P262L was retained in intracellular vesicles and did not
      localize to the ER. Upon co-expression, however, AQP2-P262L interacted with wt
      AQP2, but not with AQP2-R187C, resulting in a rescued apical membrane expression
      of AQP2-P262L. In conclusion, our study reveals a novel cellular phenotype in
      recessive NDI in that AQP2-P262L acts as a mutant in dominant NDI, except for
      that its missorting is overruled by apical sorting of wt-AQP2. Also, it
      demonstrates for the first time that the recessive inheritance of a disease
      involving a channel can be due to two cell-biological mechanisms.

PMID- 15509593
TI  - HNF1beta/TCF2 mutations impair transactivation potential through altered co
      regulator recruitment.
AB  - Mutations in the HNF1beta gene, encoding the dimeric POU-homeodomain
      transcription factor HNF1beta (TCF2 or vHNF1), cause various phenotypes including
      maturity onset diabetes of the young 5 (MODY5), and abnormalities in kidney,
      pancreas and genital tract development. To gain insight into the molecular
      mechanisms underlying these phenotypes and into the structure of HNF1beta, we
      functionally characterized eight disease-causing mutations predicted to produce
      protein truncations, amino acids substitutions or frameshift deletions in
      different domains of the protein. Truncated mutations, retaining the dimerization
      domain, displayed defective nuclear localization and weak dominant-negative
      activity when co-expressed with the wild-type protein. A frameshift mutation
      located within the C-terminal QSP-rich domain partially reduced transcriptional
      activity, whereas selective deletion of this domain abolished transactivation.
      All five missense mutations, which concern POU-specific and homeodomain residues,
      were correctly expressed and localized to the nucleus. Although having different
      effects on DNA-binding capacity, which ranged from complete loss to a mild
      reduction, these mutations exhibited a severe reduction in their transactivation
      capacity. The transcriptional impairment of those mutants, whose DNA-binding
      activity was weakly or not affected, correlated with the loss of association with
      one of the histone-acetyltransferases CBP or PCAF. In contrast to wild-type
      HNF1beta, whose transactivation potential depends on the synergistic action of
      CBP and PCAF, the activity of these mutants was not increased by the synergistic
      action of these two coactivators or by treatment with the specific histone
      deacetylase inhibitor TSA. Our findings suggest that the complex syndrome
      associated with HNF1beta-MODY5 mutations arise from either defective DNA-binding
      or transactivation function through impaired coactivator recruitment.

PMID- 15509594
TI  - Recombination hotspots and block structure of linkage disequilibrium in the human
      genome exemplified by detailed analysis of PGM1 on 1p31.
AB  - The distribution of linkage disequilibrium (LD) in the human genome has important
      consequences for the design of experiments that infer susceptibility genes for
      complex disease using association studies. Recent studies have shown a non-random
      distribution of human meiotic recombination associated with intervening tracts of
      LD. Little is known about the processes, patterns and frequency of reciprocal
      meiotic recombination in humans. However, this phenomenon can be better
      understood by the fine structure analysis of several genomic regions by mapping
      hotspots and characterizing regions with variable LD. Here, we report clustered
      hotspot activity with intervening blocks of LD within the human PGM1 gene (1p31)
      using data derived from meiotic and population studies. Earlier work has
      suggested a high recombination rate in two regions within the PGM1 gene, site A
      (exons 4-8) and site B (exons 1A-4). Sequencing of eight individuals across 6 kb
      of targeted regions in site B identified 18 informative SNPs. Individuals from
      three distinct populations, Caucasian (n=264), Chinese (n=222) and Vietnamese
      (n=187), were genotyped, and haplotypes were determined using estimate of
      haplotypes, ldmax and Arlequin. Allelic association and haplotype analysis in
      these samples revealed variable recombination rates across PGM1, demonstrating
      the presence of: (i) three hotspots and (ii) three haplotype blocks. The spatial
      arrangement of haplotype blocks was identical in all populations studied. The
      pattern of association within PGM1 represents a region decomposed into small
      blocks of LD, where increased recombination activity has disrupted the ancestral
      chromosome. Additionally, crossovers in phased data mapped preferentially to
      regions where LD collapses, which also overlap with sequence motifs.

PMID- 15509595
TI  - Iron-sulfur protein maturation in human cells: evidence for a function of
      frataxin.
AB  - The maturation of iron-sulfur (Fe/S) proteins in eukaryotes has been intensively
      studied in yeast. Hardly anything is known so far about the process in higher
      eukaryotes, even though the high conservation of the yeast maturation components
      in most Eukarya suggests similar mechanisms. Here, we developed a cell culture
      model in which the RNA interference (RNAi) technology was used to deplete a
      potential component of Fe/S protein maturation, frataxin, in human HeLa cells.
      This protein is lowered in humans with the neuromuscular disorder Friedreich's
      ataxia (FRDA). Upon frataxin depletion by RNAi, the enzyme activities of the
      mitochondrial Fe/S proteins, aconitase and succinate dehydrogenase, were
      decreased, while the activities of non-Fe/S proteins remained constant. Moreover,
      Fe/S cluster association with the cytosolic iron-regulatory protein 1 was
      diminished. In contrast, no alterations in cellular iron uptake, iron content and
      heme formation were found, and no mitochondrial iron deposits were observed upon
      frataxin depletion. Hence, iron accumulation in FRDA mitochondria appears to be a
      late consequence of frataxin deficiency. These results demonstrate (i) that
      frataxin is a component of the human Fe/S cluster assembly machinery and (ii)
      that it plays a role in the maturation of both mitochondrial and cytosolic Fe/S
      proteins.

PMID- 15509596
TI  - HyPhy: hypothesis testing using phylogenies.
AB  - The HyPhypackage is designed to provide a flexible and unified platform for
      carrying out likelihood-based analyses on multiple alignments of molecular
      sequence data, with the emphasis on studies of rates and patterns of sequence
      evolution. AVAILABILITY: http://www.hyphy.org CONTACT: muse@stat.ncsu.edu
      SUPPLEMENTARY INFORMATION: HyPhydocumentation and tutorials are available at
      http://www.hyphy.org.

PMID- 15509597
TI  - COPS--cis/trans peptide bond conformation prediction of amino acids on the basis
      of secondary structure information.
AB  - COPS predicts for all 20 naturally occurring amino acids whether the peptide bond
      in a protein is in cis or trans conformation. The algorithm is based only on
      secondary structure information of amino acid triplets without considering the
      amino acid sequence information. Conformation parameters are derived from solved
      3D structures deposited in the PDB and led to propensities based on modified Chou
      Fasman parameters. COPS analyses amino acid triplets taking only their respective
      secondary structure into consideration and upon application of a set of rules
      utilizing the conformation parameters, the N-terminal peptide bond conformation
      of the middle residue is predicted. COPS was tested on a random selection of
      protein datasets. AVAILABILITY: The COPS program and further information are
      freely available from the FMP website at http://www.fmp-berlin.de/nmr/cops
      CONTACT: labudde@fmp-berlin.de.

PMID- 15509598
TI  - LabArray: real-time imaging and analytical tool for microarrays.
AB  - Microarrays have been used to perform high-throughput genetic analyses such as
      single-nucleotide polymorphisms detection and microbial genome analysis. Some of
      these analyses require real-time monitoring of the hybridization signals with
      respect to a varying experimental condition, such as temperature. However,
      current microarray imaging and analysis packages typically do not possess such
      real-time capabilities. Therefore, microarray image analyses are often time
      consuming and labour-intensive. LabArray was developed to expedite such processes
      by enabling real-time monitoring of microarray signals. AVAILABILITY: LabArray is
      available at http://www.eng.nus.edu.sg/civil/Labarray/labarray.htm CONTACT:
      cveliuwt@nus.edu.sg SUPPLEMENTARY INFORMATION: Screenshots and instructions for
      use are available at the above website.

PMID- 15509599
TI  - MedKit: a helper toolkit for automatic mining of MEDLINE/PubMed citations.
AB  - MEDLINE/PubMed is one of the most important information sources for
      bioinformatics text mining. However, there remain limitations in working with
      MEDLINE/PubMed citations. For example, PubMed imposes an upper limit of 10,000
      for downloading PMID list or citations; and MEDLINE files are too large for most
      off-the-shelf XML parsers. We developed a Java package, MedKit, to work-around
      the limitations, as well as provide other useful functionalities, e.g. random
      sampling. Its four modules (querier, sampler, fetcher and parser) can work
      independently, or be pipelined in various combinations. It can be used as a stand
      alone GUI application, or integrated into other text-mining systems. Text mining
      researchers and others may download and use the toolkit free for non-commercial
      purposes. AVAILABILITY: http://metnetdb.gdcb.iastate.edu/medkit CONTACT:
      berleant@iastate.edu.

PMID- 15509600
TI  - Statistical analysis of domains in interacting protein pairs.
AB  - MOTIVATION: Several methods have recently been developed to analyse large-scale
      sets of physical interactions between proteins in terms of physical contacts
      between the constituent domains, often with a view to predicting new pairwise
      interactions. Our aim is to combine genomic interaction data, in which domain
      domain contacts are not explicitly reported, with the domain-level structure of
      individual proteins, in order to learn about the structure of interacting protein
      pairs. Our approach is driven by the need to assess the evidence for physical
      contacts between domains in a statistically rigorous way. RESULTS: We develop a
      statistical approach that assigns p-values to pairs of domain superfamilies,
      measuring the strength of evidence within a set of protein interactions that
      domains from these superfamilies form contacts. A set of p-values is calculated
      for SCOP superfamily pairs, based on a pooled data set of interactions from
      yeast. These p-values can be used to predict which domains come into contact in
      an interacting protein pair. This predictive scheme is tested against protein
      complexes in the Protein Quaternary Structure (PQS) database, and is used to
      predict domain-domain contacts within 705 interacting protein pairs taken from
      our pooled data set.

PMID- 15509601
TI  - Automatic extraction of gene/protein biological functions from biomedical text.
AB  - MOTIVATION: With the rapid advancement of biomedical science and the development
      of high-throughput analysis methods, the extraction of various types of
      information from biomedical text has become critical. Since automatic functional
      annotations of genes are quite useful for interpreting large amounts of high
      throughput data efficiently, the demand for automatic extraction of information
      related to gene functions from text has been increasing. RESULTS: We have
      developed a method for automatically extracting the biological process functions
      of genes/protein/families based on Gene Ontology (GO) from text using a shallow
      parser and sentence structure analysis techniques. When the gene/protein/family
      names and their functions are described in ACTOR (doer of action) and OBJECT
      (receiver of action) relationships, the corresponding GO-IDs are assigned to the
      genes/proteins/families. The gene/protein/family names are recognized using the
      gene/protein/family name dictionaries developed by our group. To achieve wide
      recognition of the gene/protein/family functions, we semi-automatically gather
      functional terms based on GO using co-occurrence, collocation similarities and
      rule-based techniques. A preliminary experiment demonstrated that our method has
      an estimated recall of 54-64% with a precision of 91-94% for actually described
      functions in abstracts. When applied to the PUBMED, it extracted over 190 000
      gene-GO relationships and 150 000 family-GO relationships for major eukaryotes.

PMID- 15509602
TI  - Vocabulon: a dictionary model approach for reconstruction and localization of
      transcription factor binding sites.
AB  - MOTIVATION: Gene expression arrays enable measurements of transcription values
      for a large number or all genes in the genome. In order to better interpret these
      results and to use them to reconstruct transcription networks, information on
      location of binding sites for regulatory proteins in the entire genome is needed.
      In particular, this represents an open problem in Escherichia coli. RESULTS: We
      describe the first implementation of dictionary-style models to the study of
      transcription factors binding sites in an entire genome. Vocabulon's unique
      feature is that it can both reconstruct binding sites characterized by unknown
      motifs and impute locations of known binding sites in long sequences by
      simultaneous search. On one hand, the dictionary model specifies a probability
      for the entire sequence taking simultaneously into account all the possible
      binding sites. This greatly reduces the number of false positives. On the other
      hand, the possibility of refining motif description, as an increasing number of
      binding sites are identified, augments the sensitivity of the method. We
      illustrate these properties with examples in E.coli. The results of gene
      expression arrays are used both to guide the search and corroborate it.

PMID- 15509603
TI  - PDBML: the representation of archival macromolecular structure data in XML.
AB  - SUMMARY: The Protein Data Bank (PDB) has recently released versions of the PDB
      Exchange dictionary and the PDB archival data files in XML format collectively
      named PDBML. The automated generation of these XML files is driven by the data
      dictionary infrastructure in use at the PDB. The correspondences between the PDB
      dictionary and the XML schema metadata are described as well as the XML
      representations of PDB dictionaries and data files.

PMID- 15509604
TI  - A new approach to prediction of short-range conformational propensities in
      proteins.
AB  - MOTIVATION: Knowledge-based potentials are valuable tools for protein structure
      modeling and evaluation of the quality of the structure prediction obtained by a
      variety of methods. Potentials of such type could be significantly enhanced by a
      proper exploitation of the evolutionary information encoded in related protein
      sequences. The new potentials could be valuable components of threading
      algorithms, ab-initio protein structure prediction, comparative modeling and
      structure modeling based on fragmentary experimental data. RESULTS: A new
      potential for scoring local protein geometry is designed and evaluated. The
      approach is based on the similarity of short protein fragments measured by an
      alignment of their sequence profiles. Sequence specificity of the resulting
      energy function has been compared with the specificity of simpler potentials
      using gapless threading and the ability to predict specific geometry of protein
      fragments. Significant improvement in threading sensitivity and in the ability to
      generate sequence-specific protein-like conformations has been achieved.

PMID- 15509605
TI  - Implementation of a gene expression index calculation method based on the PDNN
      model.
AB  - Gene expression index calculations from Affymetrix GeneChips have been dominated
      by the Affymetrix MAS, dChip, and RMA methods. A new method to estimate the gene
      expression value utilizing the probe sequence information named position
      dependent nearest-neighbor (PDNN) has been suggested by Zhang et al. (2003). Here
      we describe an open source implementation of the PDNN method for the statistical
      language R. AVAILABILITY: The package can be downloaded from
      http://www.bioconductor.org/repository/devel/package/html/affypdnn.html CONTACT:
      hbjorn@cbs.dtu.dk.

PMID- 15509606
TI  - Fast and accurate database homology search using upper bounds of local alignment
      scores.
AB  - MOTIVATION: It is widely recognized that homology search and ortholog clustering
      are very useful for analyzing biological sequences. However, recent growth of
      sequence database size makes homolog detection difficult, and rapid and accurate
      methods are required. RESULTS: We present a novel method for fast and accurate
      homology detection, assuming that the Smith-Waterman (SW) scores between all
      similar sequence pairs in a target database are computed and stored. In this
      method, SW alignment is computed only if the upper bound, which is derived from
      our novel inequality, is higher than the given threshold. In contrast to other
      methods such as FASTA and BLAST, this method is guaranteed to find all sequences
      whose scores against the query are higher than the specified threshold. Results
      of computational experiments suggest that the method is dozens of times faster
      than SSEARCH if genome sequence data of closely related species are available.

PMID- 15509607
TI  - Local correlation of expression profiles with gene annotations--proof of concept
      for a general conciliatory method.
AB  - MOTIVATION: Integrated analysis of expression data and gene ontology annotations
      is a prime example of biological data that need co-explanatory interpretation.
      This particular application is used to validate a new method for integrated
      analysis of varied biological information. RESULTS: The proposed method consists
      of determining local correlation coefficients and the corresponding P-values
      calculated per biological entity. This measure considers the combined intensity
      and significance of the agreement or disagreement, between two data sources about
      the same biological entity. The method is applied to the integrated analysis of
      gene expression and annotation of two gene sets, one from yeast and other from
      mouse. The potential of the method to generate accurate mechanistic hypothesis is
      also demonstrated. Specially, negative correlation results pose a new kind of
      biological hypothesis. Method performance was compared with annotation enrichment
      methods, and optimal conditions for the superiority of local correlation results
      are discussed.

PMID- 15509608
TI  - Profile-based detection of microRNA precursors in animal genomes.
AB  - MOTIVATION: MicroRNAs (miRNA) are essential 21-22 nt regulatory RNAs produced
      from larger hairpin-like precursors. Local sequence alignment tools such as BLAST
      are able to identify new members of known miRNA families, but not all of them. We
      set out to estimate how many new miRNAs could be recovered using a profile-based
      strategy such as that implemented in the ERPIN program. RESULTS: We constructed
      alignments for 18 miRNA families and performed ERPIN searches on animal genomes.
      Results were compared to those of a WU-BLAST search at the same E-value cutoff.
      The two combined approaches produced 265 new miRNA candidates that were not found
      in miRNA databases. About 17% of hits were ERPIN specific. They showed better
      structural characteristics than BLAST-specific hits and included interesting
      candidates such as members of the miR-17 cluster in Tetraodon. Profile-based RNA
      detection will be an important complement of similarity search programs in the
      completion of miRNA collections.

PMID- 15509609
TI  - ColorHOR--novel graphical algorithm for fast scan of alpha satellite higher-order
      repeats and HOR annotation for GenBank sequence of human genome.
AB  - MOTIVATION: GenBank data are at present lacking alpha satellite higher-order
      repeat (HOR) annotation. Furthermore, exact HOR consensus lengths have not been
      reported so far. Given the fast growth of sequence databases in the centromeric
      region, it is of increasing interest to have efficient tools for computational
      identification and analysis of HORs from known sequences. RESULTS: We develop a
      graphical user interface method, ColorHOR, for fast computational identification
      of HORs in a given genomic sequence, without requiring a priori information on
      the composition of the genomic sequence. ColorHOR is based on an extension of the
      key-string algorithm and provides a color representation of the order and
      orientation of HORs. For the key string, we use a robust 6 bp string from a
      consensus alpha satellite and its representative nature is tested. ColorHOR
      algorithm provides a direct visual identification of HORs (direct and/or reverse
      complement). In more detail, we first illustrate the ColorHOR results for human
      chromosome 1. Using ColorHOR we determine for the first time the HOR annotation
      of the GenBank sequence of the whole human genome. In addition to some HORs,
      corresponding to those determined previously biochemically, we find new HORs in
      chromosomes 4, 8, 9, 10, 11 and 19. For the first time, we determine exact
      consensus lengths of HORs in 10 chromosomes. We propose that the HOR assignment
      obtained by using ColorHOR be included into the GenBank database.

PMID- 15509610
TI  - The construction of amino acid substitution matrices for the comparison of
      proteins with non-standard compositions.
AB  - MOTIVATION: Amino acid substitution matrices play a central role in protein
      alignment methods. Standard log-odds matrices, such as those of the PAM and
      BLOSUM series, are constructed from large sets of protein alignments having
      implicit background amino acid frequencies. However, these matrices frequently
      are used to compare proteins with markedly different amino acid compositions,
      such as transmembrane proteins or proteins from organisms with strongly biased
      nucleotide compositions. It has been argued elsewhere that standard matrices are
      not ideal for such comparisons and, furthermore, a rationale has been presented
      for transforming a standard matrix for use in a non-standard compositional
      context. RESULTS: This paper presents the mathematical details underlying the
      compositional adjustment of amino acid or DNA substitution matrices.

PMID- 15509611
TI  - Inferring pathways from gene lists using a literature-derived network of
      biological relationships.
AB  - MOTIVATION: A number of omic technologies such as transcriptional profiling,
      proteomics, literature searches, genetic association, etc. help in the
      identification of sets of important genes. A subset of these genes may act in a
      coordinated manner, possibly because they are part of the same biological
      pathway. Interpreting such gene lists and relating them to pathways is a
      challenging task. Databases of biological relationships between thousands of
      mammalian genes can help in deciphering omics data. The relationships between
      genes can be assembled into a biological network with each protein as a node and
      each relationship as an edge between two proteins (or nodes). This network may
      then be searched for subnetworks consisting largely of interesting genes from the
      omics experiment. The subset of genes in the subnetwork along with the web of
      relationships between them helps to decipher the underlying pathways. Finding
      such subnetworks that maximally include all proteins from the query set but few
      others is the focus for this paper. RESULTS: We present a heuristic algorithm and
      a scoring function that work well both on simulated data and on data from known
      pathways. The scoring function is an extension of a previous study for a single
      biological experiment. We use a simple set of heuristics that provide a more
      efficient solution than the simulated annealing method. We find that our method
      works on reasonably complex curated networks containing approximately 9000
      biological entities (genes and metabolites), and approximately 30,000 biological
      relationships. We also show that our method can pick up a pathway signal from a
      query list including a moderate number of genes unrelated to the pathway. In
      addition, we quantify the sensitivity and specificity of the technique.

PMID- 15509612
TI  - An enzyme mechanism language for the mathematical modeling of metabolic pathways.
AB  - MOTIVATION: As a first step toward the elucidation of the systems biology of
      complex biological systems, it was our goal to mathematically model common enzyme
      catalytic and regulatory mechanisms that repeatedly appear in biological
      processes such as signal transduction and metabolic pathways. RESULTS: We
      describe kMech, a Cellerator language extension that describes a suite of enzyme
      mechanisms. Each enzyme mechanism is parsed by kMech into a set of fundamental
      association-dissociation reactions that are translated by Cellerator into
      ordinary differential equations that are numerically solved by Mathematica. In
      addition, we present methods that use commonly available kinetic measurements to
      estimate rate constants required to solve these differential equations.

PMID- 15509613
TI  - Relational patterns of gene expression via non-metric multidimensional scaling
      analysis.
AB  - MOTIVATION: Microarray experiments result in large-scale data sets that require
      extensive mining and refining to extract useful information. We demonstrate the
      usefulness of (non-metric) multidimensional scaling (MDS) method in analyzing a
      large number of genes. Applying MDS to the microarray data is certainly not new,
      but the existing works are all on small numbers (< 100) of points to be analyzed.
      We have been developing an efficient novel algorithm for non-metric MDS (nMDS)
      analysis for very large data sets as a maximally unsupervised data mining device.
      We wish to demonstrate its usefulness in the context of bioinformatics
      (unraveling relational patterns among genes from time series data in this paper).
      RESULTS: The Pearson correlation coefficient with its sign flipped is used to
      measure the dissimilarity of the gene activities in transcriptional response of
      cell-cycle-synchronized human fibroblasts to serum. These dissimilarity data have
      been analyzed with our nMDS algorithm to produce an almost circular relational
      pattern of the genes. The obtained pattern expresses a temporal order in the data
      in this example; the temporal expression pattern of the genes rotates along this
      circular arrangement and is related to the cell cycle. For the data we analyze in
      this paper we observe the following. If an appropriate preparation procedure is
      applied to the original data set, linear methods such as the principal component
      analysis (PCA) could achieve reasonable results, but without data preprocessing
      linear methods such as PCA cannot achieve a useful picture. Furthermore, even
      with an appropriate data preprocessing, the outcomes of linear procedures are not
      as clear-cut as those by nMDS without preprocessing.

PMID- 15509614
TI  - Antibiotic susceptibility of 65 isolates of Burkholderia pseudomallei and
      Burkholderia mallei to 35 antimicrobial agents.
AB  - OBJECTIVES: Fifty isolates of Burkholderia pseudomallei and 15 isolates of
      Burkholderia mallei were tested for their susceptibilities to 35 antimicrobial
      agents, including agents not previously tested against these bacteria. METHODS:
      MICs were determined by agar dilution in Mueller-Hinton medium. RESULTS: Among
      the antibiotics tested, lower MICs were obtained with imipenem, ceftazidime,
      piperacillin, piperacillin/tazobactam, doxycycline and minocycline.
      Fluoroquinolones and aminoglycosides had poor activities. A single clinical
      isolate of B. pseudomallei was resistant to ceftazidime, co-amoxiclav and
      doxycycline but remained susceptible to imipenem. CONCLUSIONS: Although B. mallei
      MICs are often lower, the overall results underline the importance of resistance
      in both species. The susceptibilities measured are consistent with the current
      recommendations for the treatment of B. pseudomallei and B. mallei infections.

PMID- 15509615
TI  - Pitfalls of polymyxin antimicrobial susceptibility testing of Pseudomonas
      aeruginosa isolated from cystic fibrosis patients.
AB  - OBJECTIVES AND METHODS: With their potent activity against Gram-negative
      bacteria, the polymyxins are important alternative antibiotics for cystic
      fibrosis (CF) patients. A retrospective evaluation of polymyxin activity against
      6001 Pseudomonas aeruginosa, 150 Achromobacter xylosoxidans and 506
      Stenotrophomonas maltophilia CF isolates was initiated. In addition, we looked at
      how polymyxin susceptibility testing was affected by the testing method (agar
      dilution versus microdilution), the agent (polymyxin E versus polymyxin B),
      incubation time (24 h versus 48 h) and by different interpretative criteria
      (German DIN, French FSM, British BSAC). RESULTS: Polymyxin B exhibited reasonable
      activity against P. aeruginosa (MIC(90)< or =2 mg/L), whereas it was less active
      against A. xylosoxidans (MIC(90)< or =16 mg/L) and S. maltophilia (MIC(90)< or
      =16 mg/L). During 2000-2002, polymyxin B resistance in P. aeruginosa, S.
      maltophilia and A. xylosoxidans was found to be 6.7%, 17.0% and 29.9%
      (corresponding to 12.4%, 20.7% and 35.4% of infected patients), respectively.
      When the agar dilution method was used, polymyxin E exhibited higher MICs than
      polymyxin B. The microdilution method produced lower polymyxin MICs than the agar
      dilution method. Therefore, the microdilution MICs after prolonged incubation (48
      h) and the agar dilution MICs of polymyxin B correlated best (AUC of 0.93, r(2)
      of 0.44 and s of 0.83). CONCLUSIONS: Polymyxin resistance among common CF
      pathogens is not rare, thus underlining the necessity of accurate susceptibility
      testing. When compared with the agar dilution method, it was found that the
      microdilution method is a valid, rapid and cost effective alternative for the
      determination of polymyxin activity. The performance of the microdilution method
      was most reliable after prolonged incubation (48 h) at a susceptibility
      breakpoint of < or =4 mg/L according to the BSAC guidelines (specificity 91%,
      sensitivity 89%, 1.5% very major errors).

PMID- 15509616
TI  - A novel murine model of cerebral scedosporiosis: lack of efficacy of amphotericin
      B.
AB  - OBJECTIVES: Cerebral scedosporiosis is a life-threatening infection that is
      difficult to treat. The aim of this work was to develop a murine model of
      cerebral infection by Scedosporium apiospermum using intracranial inoculation and
      to use this model to evaluate the efficacy of amphotericin B deoxycholate and
      liposomal amphotericin B. METHODS: Mice were rendered neutropenic by
      intraperitoneal cyclophosphamide and intravenous (iv) 5-fluorouracil
      administration. Animals were infected with iv or intracranial inoculation of 1 x
      10(4), 5 x 10(4) or 5 x 10(5) cfu of a clinical strain of S. apiospermum. Tissue
      burden reduction was determined in kidneys and brain 4 days after the infection.
      Efficacy of amphotericin B and liposomal amphotericin B (0.8 mg/kg/day
      intraperitoneally and 40 mg/kg/day iv, respectively) was evaluated in neutropenic
      mice infected iv or intracranially with 5 x 10(4) cfu. Survival was analysed with
      the log-rank test. Fungal burden values of different groups were compared using
      the Mann-Whitney U-test. RESULTS: In our model, intracranial infection produced a
      higher fungal load in the brain and a lower fungal load in the kidney than iv
      inoculation. Survival of animals infected intracranially and treated with
      amphotericin B or liposomal amphotericin B (mean survival time = 8.3 and 9.2
      days, respectively) was not different from the control group (P=0.58 and 0.85,
      respectively). CONCLUSIONS: We have developed a murine model of cerebral
      scedosporiosis, which may be useful for studying various pathological aspects of
      this infection and evaluating new therapeutic approaches. Amphotericin B and
      liposomal amphotericin B were unable to resolve the infection.

PMID- 15509617
TI  - Alternative dosing regimens of liposomal amphotericin B (AmBisome) effective in
      treating murine systemic candidiasis.
AB  - OBJECTIVES: This study was done to determine whether high dose AmBisome (4-20
      mg/kg), given intermittently, could reduce the frequency of dosing needed to
      treat murine systemic candidiasis when compared with conventional daily
      treatment. METHODS: Mice were immunosuppressed with cyclophosphamide every 3
      days, beginning day -3 before challenge with log(10) 5.0 cfu Candida albicans.
      Treatment was begun 48-72 h post-challenge with daily or intermittent dose
      regimens of AmBisome, followed by determination of kidney cfu for up to 1 month
      post-treatment. RESULTS: A single AmBisome dose of 4 mg/kg was as effective as
      four daily, 1 mg/kg treatments. A total of 8 mg/kg, given as 4 mg/kg on days 2
      and 4, or as 5 mg/kg on day 2 followed by 1 mg/kg on days 3, 4, and 5, also
      produced comparable efficacy. While 20 mg/kg given day 2, 4 and 6 post-challenge
      as a 1 week loading dose, followed by one 10 mg/kg treatment on day 13, decreased
      the fungal burden by up to 5 logs compared with controls (log(10) 2.3 cfu/g and
      log(10) 7.5 cfu/g, respectively), 20 mg/kg given Monday, Wednesday and Friday for
      5 weeks, reduced the fungal burden to undetectable levels (i.e. log(10) 1.0 cfu).
      CONCLUSIONS: Significant reduction or clearance of kidney cfu, following
      intermittent, high dose AmBisome treatment, indicated that non-daily dosing
      regimens could be successfully used instead of conventional daily dosing to treat
      established C. albicans infection in immunosuppressed mice.

PMID- 15509618
TI  - VEGF overexpression induces post-ischaemic neuroprotection, but facilitates
      haemodynamic steal phenomena.
AB  - Therapeutic angiogenesis with vascular endothelial growth factor (VEGF) is a
      clinically promising strategy in ischaemic disease. The pathophysiological
      consequences of enhanced vessel formation, however, are poorly understood. We
      established mice overexpressing human VEGF165 under a neuron-specific promoter,
      which exhibited an increased density of brain vessels under physiological
      conditions and enhanced angiogenesis after brain ischaemia. Following transient
      intraluminal middle cerebral artery (MCA) occlusions, VEGF overexpression
      significantly alleviated neurological deficits and infarct volume, and reduced
      disseminated neuronal injury and caspase-3 activity, confirming earlier
      observations that VEGF has neuroprotective properties. Brain swelling was not
      influenced in VEGF-overexpressing animals, while sodium fluorescein extravasation
      was moderately increased, suggesting that VEGF induces a mild blood-brain barrier
      leakage. To elucidate whether enhanced angiogenesis improves regional cerebral
      blood flow in the ischaemic brain, [14C]iodoantipyrine autoradiography was
      performed. Autoradiographies revealed that VEGF induces haemodynamic steal
      phenomena with reduced blood flow in ischaemic areas and increased flow values
      only outside the MCA territory. Our data demonstrate that VEGF protects neurons
      from ischaemic cell death by a direct action rather than by promoting
      angiogenesis, and suggest that strategies aiming at increasing vascular density
      in the whole brain, e.g. by VEGF overexpression, may worsen rather than improve
      cerebral haemodynamics after stroke.

PMID- 15509619
TI  - Abnormal excitability of premotor-motor connections in de novo Parkinson's
      disease.
AB  - The dorsal premotor cortex (PMd) is abnormally active in patients with idiopathic
      Parkinson's disease. This has been interpreted as a functional correlate of
      adaptive plasticity within the motor system to compensate for deficient
      activation of striato-mesial-frontal projections in these patients. Whether
      abnormal PMd activity influences excitability in the primary motor cortex (M1) in
      untreated Parkinson's disease patients and how this premotor-motor interaction
      might be altered by l-dopa is unclear. To this end, we studied the effects of 1
      Hz premotor repetitive transcranial magnetic stimulation (rTMS) on M1
      excitability in 10 previously untreated non-tremulous Parkinson's disease
      patients before (day 1) and after (day 8) their first ever l-dopa treatment and
      compared the results with those of a group of nine age- and sex-matched healthy
      controls. In each rTMS session, 1200 pulses of 1 Hz rTMS were applied at an
      intensity of 80% active motor threshold (AMT) to the PMd contralateral to the
      clinically more affected side in Parkinson's disease patients and to the left PMd
      in healthy controls. Intracortical paired pulse excitability of ipsilateral M1
      was probed using a TMS paired pulse paradigm where subthreshold conditioning
      pulses (80% of AMT) were given 2-15 ms prior to a suprathreshold test pulse. In
      Parkinson's disease patients, abnormal baseline intracortical excitability at an
      interstimulus interval (ISI) of 5 ms was normalized by premotor rTMS. In
      contrast, rTMS led to an increased excitability at an ISI of 5 ms in healthy
      controls. Premotor rTMS effects lasted longer (for at least a week) in patients.
      These results show that the modifiability of premotor-motor connections is
      abnormal in untreated Parkinson's disease. A single dose of l-dopa reversed, i.e.
      normalized, the direction of excitability changes in M1 following premotor rTMS
      in Parkinson's disease patients, suggesting that dopamine depletion directly or
      indirectly influences premotor-motor interactions in Parkinson's disease. The
      rTMS conditioning approach described here provides a promising tool to delineate
      further the excitability changes in frontal motor areas in response to
      progressive degeneration of nigrostriatal dopaminergic neurons and also to
      chronic l-dopa treatment in Parkinson's disease.

PMID- 15509620
TI  - Axonal protection in experimental autoimmune neuritis by the sodium channel
      blocking agent flecainide.
AB  - Inflammatory demyelinating neuropathies such as Guillain-Barre syndrome (GBS) and
      its animal model, experimental autoimmune neuritis (EAN), are typically acute
      monophasic diseases of the PNS that can leave affected individuals with permanent
      disability due primarily to axonal degeneration. The mechanisms underlying the
      degeneration are not understood, but we have previously shown in vitro and in
      vivo that axons can degenerate when exposed to the inflammatory mediator nitric
      oxide, and that axons can be protected by application of the sodium channel
      blocking agent, flecainide. Here we examine whether flecainide administration can
      similarly reduce axonal degeneration in the periphery in animals with EAN. EAN
      was induced in Lewis rats (n = 116, in three independent trials), and rats
      received either flecainide (Flec) (30 mg/kg/day) or vehicle (Veh) from the onset
      of disease expression. Flecainide administration significantly reduced the mean
      (SD) scores for neurological deficit at both the peak of disease (Flec: 5.7
      (2.7), Veh: 8.0 (3.6), P < 0.001) and at the termination of the trials 25-29 days
      post-inoculation (Flec: 2.2 (2.4), Veh: 4.2 (4.2), P < 0.001). Histological
      examination of the tibial nerve of EAN animals revealed that flecainide provided
      significant protection against axonal degeneration so that 80.0% of the normal
      number of axons survived in flecainide-treated rats compared with 62.8% in
      vehicle-treated rats (P < 0.01). These findings may indicate a novel avenue for
      axonal protection in GBS and other inflammatory demyelinating neuropathies.

PMID- 15509621
TI  - Reciprocal inhibition and corticospinal transmission in the arm and leg in
      patients with autosomal dominant pure spastic paraparesis (ADPSP).
AB  - The pathophysiological mechanisms underlying the development of spasticity are
      not clear, but the excitability of the disynaptic reciprocal inhibitory pathway
      is affected in many patients with spasticity of different origin. Patients with
      genetically identified autosomal dominant pure spastic paraparesis (ADPSP)
      develop spasticity and paresis in the legs, but usually have no symptoms in the
      arms. Comparison of the spinal and supraspinal control of the legs and arms in
      these patients may therefore provide valuable information about the
      pathophysiology of spasticity. In the present study, we tested the hypothesis
      that one of the pathophysiological mechanisms of spasticity in these patients is
      abnormal corticospinal transmission and that this may lead to decreased
      reciprocal inhibition. Ten patients and 15 healthy age-matched control subjects
      were investigated. The patients were all spastic in the legs (with hyperactive
      tendon reflexes, increased muscle tone and Babinski sign), but had no
      neurological symptoms in the arms (except for one patient). Disynaptic reciprocal
      Ia inhibition of flexor carpi radialis (FCR) and soleus (SOL) motoneurons was
      measured (as the depression of the background FCR and SOL EMG activity and as the
      short latency inhibition of the FCR and SOL H-reflex evoked by radial and
      peroneal nerve stimulation). In addition, the latency of motor evoked potentials
      (MEPs) in the FCR muscle and the tibialis anterior (TA) muscle was measured. In
      the patients, the mean reciprocal inhibition was normal in the arms, while it was
      significantly decreased in the leg compared with the healthy subjects. In the
      patients, the average latency of MEPs in the FCR muscle was normal, while the
      latency to the MEP in TA muscle was significantly longer than that found in
      healthy subjects. Four patients, however, differed from the other patients by
      having significant reciprocal inhibition in the leg and a significantly shorter
      latency of TA MEPs than found in the other patients. The six patients without
      reciprocal inhibition in the leg instead had significant short latency
      facilitation of the SOL H-reflex and a longer TA MEP latency than seen in the
      healthy subjects and in the four patients with retained reciprocal inhibition.
      These findings support the hypothesis that disynaptic reciprocal inhibition and
      short latency facilitation are involved in the development of spasticity and,
      furthermore, they suggest a positive correlation between impairment of
      corticospinal transmission and decrease of reciprocal inhibition/appearance of
      reciprocal facilitation.

PMID- 15509622
TI  - Pursuit eye movement deficits in autism.
AB  - Oculomotor studies provide a novel strategy for evaluating the functional
      integrity of multiple brain systems and cognitive processes in autism. The
      current study compared pursuit eye movements of 60 high-functioning individuals
      with autism and 94 intelligence quotient, age and gender matched healthy
      individuals using ramp and oscillating target tasks. Individuals with autism had
      normal pursuit latency, but reduced closed-loop pursuit gain when tracking both
      oscillating and ramp targets. This closed-loop deficit was similar for leftward
      and rightward pursuit, but the difference between individuals with autism and
      their age-matched peers was more apparent after mid-adolescence, suggesting
      reduced maturational achievement of the pursuit system in autism. Individuals
      with autism also had lower open-loop pursuit gain (initial 100 ms of pursuit) and
      less accurate initial catch-up saccades during a foveofugal step-ramp task, but
      these deficits were only seen when targets moved into the right visual field.
      Pursuit performance in both open- and closed-loop phases was correlated with
      manual praxis in individuals with autism. Bilateral disturbances in the ability
      to use internally generated extraretinal signals for closed-loop pursuit
      implicate frontostriatal or cerebellar circuitry. The hemifield specific deficit
      in open-loop pursuit demonstrates a lateralized disturbance in the left
      extrastriate areas that extract visual motion information, or in the transfer of
      visual motion information to the sensorimotor areas that transform visual
      information into appropriate oculomotor commands.

PMID- 15509623
TI  - The spectrum of pathological involvement of the striatonigral and
      olivopontocerebellar systems in multiple system atrophy: clinicopathological
      correlations.
AB  - Multiple system atrophy (MSA) has varying clinical (MSA-P versus MSA-C) and
      pathological [striatonigral degeneration (SND) versus olivopontocerebellar
      atrophy (OPCA)] phenotypes. To investigate the spectrum of clinicopathological
      correlations, we performed a semi-quantitative pathological analysis of 100 MSA
      cases with well-characterized clinical phenotypes. In 24 areas, chosen from both
      the striatonigral (StrN) and olivopontocerebellar (OPC) regions, the severity of
      neuronal cell loss and gliosis as well as the frequency of glial
      (oligodendroglial) cytoplasmic inclusions (GCIs) and neuronal cytoplasmic
      inclusions (NCIs) were determined. Clinical information was abstracted from the
      patients' medical records, and the severity of bradykinesia in the first year of
      disease onset and in the final stages of disease was graded retrospectively. The
      degree of levodopa responsiveness and the presence or absence of cerebellar
      ataxia and autonomic symptoms were also recorded. We report that 34% of the cases
      were SND- and 17% were OPCA-predominant, while the remainder (49%) had equivalent
      SND and OPCA pathology. We found a significant correlation between the frequency
      of GCIs and the severity of neuronal cell loss, and between these pathological
      changes and disease duration. Our data also suggest that GCIs may have more
      influence on the OPC than on the StrN pathology. Moreover, we raise the
      possibility that a rapid process of neuronal cell loss, which is independent of
      the accumulation of GCIs, occurs in the StrN region in MSA. There was no
      difference in the frequency of NCIs in the putamen, pontine nucleus and inferior
      olivary nucleus between the SND and OPCA subtypes of MSA, confirming that this
      pathological abnormality is not associated with a particular subtype of the
      disease. In the current large post-mortem series, 10% of the cases had associated
      Lewy body pathology, suggesting that this is not a primary process in MSA. As
      might be expected, there was a significant difference in the severity of
      bradykinesia and the presence of cerebellar signs between the pathological
      phenotypes: the SND phenotype demonstrates the most severe bradykinesia and the
      OPCA phenotype the more frequent occurrence of cerebellar signs, confirming that
      the clinical phenotype is dependent on the distribution of pathology within the
      basal ganglia and cerebellum. Putaminal involvement correlated with a poor
      levodopa response in MSA. Our finding that relatively mild involvement of the
      substantia nigra is associated clinically with manifest parkinsonism, while more
      advanced cerebellar pathology is required for ataxia, may explain why the
      parkinsonian presentation is predominant over ataxia in MSA.

PMID- 15509624
TI  - Resistance of human adult oligodendrocytes to AMPA/kainate receptor-mediated
      glutamate injury.
AB  - Multiple sclerosis is an inflammatory disease of the CNS leading to the
      destruction of oligodendrocytes (OLs), myelin sheaths and axons. The mediators of
      tissue injury remain unknown. Glutamate, which can be released by activated
      immune cells or produced within the CNS, has been implicated as a potential
      mediator of tissue injury in multiple sclerosis. alpha-Amino-3-hydroxy-5-methyl-4
      isoxazole proprionic acid (AMPA) and kainate are highly toxic when added to
      rodent OL cultures. Using OLs derived from human adult surgical specimens, we
      investigated AMPA/kainate receptor expression and the effects of receptor
      stimulation on the viability of human OLs. We find that human adult OLs in vitro
      express low levels of ionotropic glutamate receptors and are resistant to
      excitotoxicity mediated by high and sustained doses of AMPA or kainate, even when
      receptor desensitization is blocked. In contrast, rat OLs show strong AMPA
      receptor expression and are susceptible to excitotoxicity, as previously
      demonstrated. Furthermore, we show in human brain sections that OLs do not
      express AMPA receptors in situ and that glial expression of AMPA receptors is
      limited to astrocytes. The apparent lack of glutamate receptor expression on
      human OLs and their resistance to AMPA/kainate toxicity should be considered when
      postulating mechanisms of tissue injury in multiple sclerosis.

PMID- 15509625
TI  - Prevalence of Sjogren's syndrome in ambulatory patients according to the American
      European Consensus Group criteria.
AB  - OBJECTIVE: To estimate the prevalence of Sjogren's syndrome (SS) in ambulatory
      patients attending a tertiary care centre, according to the American-European
      Consensus Group criteria, using a structured approach. METHODS: Three hundred
      patients from rheumatology and internal medicine clinics were randomly chosen.
      During the screening phase, a face-to-face interview, a screening questionnaire,
      a Schirmer-I test and a wafer test were carried out in all patients. During the
      second phase, patients with positive screening had confirmatory tests including
      fluorescein staining test, non-stimulated whole salivary flow and autoantibody
      testing. Confirmatory tests were also done in 13 patients with negative
      screening. In the last phase, lip biopsy was proposed to those patients who met
      pre-established criteria. RESULTS: Females constituted 79% of the study
      population. The mean age of the subjects was 42.8+/-15.7 yr. Two hundred and
      twenty patients (73%) had positive screening. Fifty-five (27%) out of 204
      patients evaluated showed keratoconjunctivitis sicca and 28 (13%) out of 215
      patients xerostomia. One hundred and sixty-eight patients met criteria for lip
      biopsy and it was performed in 80 subjects who accepted the procedure. Focal
      sialoadenitis was demonstrated in 39 patients (49%), but only 28 of them met
      criteria for SS. In total, 40 patients were classified as SS. The minimum
      prevalence of SS in the population studied was 13.3% (95% CI 9.5-17.1%). The
      structured approach used in this study allowed 24 (60%) undiagnosed cases of SS
      to be identified. CONCLUSION: SS is common among ambulatory patients attending a
      tertiary care centre and in most of them it is undiagnosed.

PMID- 15509626
TI  - Lack of circulating autoantibodies to bone morphogenetic protein receptor-II or
      activin receptor-like kinase 1 in mixed connective tissue disease patients with
      pulmonary arterial hypertension.
AB  - OBJECTIVES: To examine whether autoantibodies against bone morphogenetic protein
      receptor-II (BMPR-II) or activin receptor-like kinase 1 (ALK-1) are associated
      with pulmonary arterial hypertension (PAH) in patients with mixed connective
      tissue disease (MCTD). METHODS: We studied sera from 37 MCTD patients with or
      without PAH, six patients with idiopathic PAH, and 30 healthy controls.
      Circulating anti-BMPR-II and anti-ALK-1 antibodies were detected using
      immunoprecipitation of recombinant antigens generated by in vitro
      transcription/translation and indirect immunofluorescence of cultured cells that
      were induced to express these antigens by gene transfer. Anti-BMPR-II antibodies
      were further examined by immunoprecipitation and immunoblotting using a
      recombinant fragment of the extracellular domain of BMPR-II. RESULTS: Serum anti
      BMPR-II and anti-ALK-1 autoantibodies were not detected in MCTD patients
      irrespective of the presence or absence of PAH, or in patients with idiopathic
      PAH. CONCLUSIONS: Our finding does not support the hypothesis that autoantibody
      mediated dysregulation of signals through BMPR-II or ALK-1 contributes to the
      development of PAH in patients with connective tissue diseases.

PMID- 15509627
TI  - Clinical and pathological differences between Mikulicz's disease and Sjogren's
      syndrome.
AB  - OBJECTIVE: Mikulicz's disease (MD) has been included within the diagnosis of
      primary Sjogren's syndrome (SS), but represents a unique condition involving
      enlargement of the lachrymal and salivary glands and characterized by few
      autoimmune reactions and good responsiveness to glucocorticoids. We have
      previously described elevated immunoglobulin (Ig) G4 in the serum of four
      patients with MD. In this paper, we accumulated more MD cases and undertook
      clinical and histopathological analysis of these patients to clarify differences
      between MD and SS. METHODS: We diagnosed seven patients with MD according to the
      following criteria: (i) visual confirmation of symmetrical and persistent
      swelling in more than two lachrymal and major salivary glands; (ii) prominent
      mononuclear infiltration of lachrymal and salivary glands; and (iii) exclusion of
      other diseases that present with glandular swelling, such as sarcoidosis and
      lymphoproliferative disease. We summarized the clinical and serological
      characteristics (IgG subclasses and IFN-gamma/IL-4 ratio) of seven patients with
      MD, compared with SS with glandular swelling (SSw) and without glandular swelling
      (SSo). After steroid administration, we analysed changes in IgG subclasses in MD.
      Labial salivary gland specimens in MD, SSw and SSo were stained with anti-IgG4
      antibodies. RESULTS: The concentration (+/-s.d.) of IgG4 was 1169.7 +/- 892.2
      mg/dl in MD, 24.4 +/- 7.0 mg/dl in SSw (P<0.005) and 82.6 +/- 189.7 mg/dl in SSo
      (P<0.005). The IFN-gamma/IL-4 ratio was 0.392 +/- 0.083 (0.78 +/- 0.23/2.14 +/-
      0.31 IU/pg) in MD, 0.004 +/- 0.002 (0.20 +/- 0.07/57.02 +/- 14.05 IU/pg) in SSw
      (P<0.05) and 0.012 +/- 0.009 (0.58 +/- 0.86/116.24 +/- 207.65 IU/pg) in SSo
      (P<0.05). The concentration (+/-s.d.) of IgG4 in MD decreased to 254.0 +/- 50.3
      mg/dl (P<0.05) after glucocorticoid treatment. Histopathologically, only MD was
      associated with prominent infiltration of IgG4-positive plasmacytes into
      lachrymal and salivary glands. CONCLUSION: Mikulicz's disease is quite different
      from SS clinically and histopathologically. MD is suggested to be an IgG4-related
      systemic disease.

PMID- 15509628
TI  - Prospects for B-cell-targeted therapy in autoimmune disease.

PMID- 15509630
TI  - Development of prototypes of half-mask facepieces for Koreans using the 3D
      digitizing design method: a pilot study.
AB  - In the Korean market there are several respirators for industrial purposes. Some
      of them are imported from global manufacturers such as 3M, and the others are
      developed by domestic companies. However, some of the locally made respirators
      have a face-seal leakage problem because they were not designed taking into
      account Korean facial characteristics. This pilot study was conducted to develop
      three face models for a half-mask based on the Korean fit-test panel and also to
      design three well-fitting silicon prototypes (large, medium and small) for Korean
      faces. For a test panel, 50 subjects were selected on the basis of lip length and
      face length. Shapes of faces from the test panel were scanned by a 3D scanner
      (Vivid 900, Minolta). The facial dimension scales for three size groups were
      established through statistical analysis. To ensure that the shapes fit the mean
      facial dimensions of each size group, similarly shaped sample faces were selected
      from the test panel. Mean faces with representative facial dimensions as well as
      face models (mannequins) were made by the Rapid Prototyper (RP; Z400, Z Corps,
      USA). These were reshaped to fit the mean faces by clay-modeling. The face models
      were digitized to recheck the fit of the facial dimensions. On the basis of the
      face models, three types of masks were developed through digital modeling, and
      tangible models were prototyped by RP. Three differently sized prototype masks
      were made with silicon and examined by simple naked eye test. This procedure
      established the mask design process based on digital technology; it can be
      applied for similar design projects in the future. Further study is needed to
      verify whether these prototypes would be a good fit for Korean faces.

PMID- 15509629
TI  - Increase of peripheral CXCR3 positive T lymphocytes upon treatment of RA patients
      with TNF-alpha inhibitors.
AB  - OBJECTIVE: To explore the regulation of factors involved in lymphocyte
      trafficking in patients with rheumatoid arthritis (RA) undergoing treatment with
      tumour necrosis factor alpha (TNF-alpha) inhibitors. METHODS: We examined 14
      consecutive patients with RA according to ACR criteria prior to and during
      treatment with TNF-alpha inhibitors (seven etanercept, seven infliximab) and
      determined disease activity using the Disease Activity Score (DAS-28). Peripheral
      blood mononuclear cells were isolated before and after 6 and 14 weeks of
      treatment and analysed immediately for CD3, CD4 and CD8, expression of chemokine
      receptors CXCR3 and CCR4, CD45RO phenotype and for expression of interferon gamma
      (IFN-gamma) and interleukin 4 (IL-4) using four-colour flow cytometry. RESULTS:
      We found significant increases in CD4 and CD8 T lymphocytes expressing CXCR3
      after 6 and 14 weeks. The overall proportion of T lymphocytes expressing CCR4
      appeared unchanged. More than half of peripheral CD4 T lymphocytes showed a
      memory phenotype (CD45RO), with a non-significant increase under TNF-alpha
      inhibition. Upon activation, up to 30% of CXCR3(+)/CD4 T cells expressed IFN
      gamma, while IL-4-expressing cells were rare. There was a robust negative
      correlation between CXCR3(+)/CD4 T lymphocytes and DAS-28. CONCLUSIONS: TNF-alpha
      inhibition with infliximab and etanercept results in sustained accumulation of
      CXCR3 positive T lymphocytes in the peripheral blood of RA patients. This
      suggests altered lymphocyte trafficking during TNF-alpha inhibition.

PMID- 15509631
TI  - In vitro percutaneous penetration of five pesticides--effects of molecular weight
      and solubility characteristics.
AB  - This study examined the in vitro percutaneous penetration of five pesticides
      covering a wide range of solubilities and different molecular weights, which
      allowed discussion of penetration of single pesticides as well as a comparison
      between penetration characteristics of different pesticides. The five pesticides
      were the fungicides methiocarb, pirimicarb and prochloraz; the growth retardant
      paclobutrazol; and the insecticide dimethoate. An experimental model with static
      diffusion cells mounted with human breast skin was used, and pesticide
      concentrations were quantified by high-performance liquid chromatography.
      Molecular weight as well as solubility affected dermal penetration and skin
      deposition. Thus, we conclude that for the passage of our test substances from
      the donor phase, through the skin, into the receptor, a too high as well as a too
      low lipophilicity may limit the rate and degree of skin penetration. Furthermore,
      the importance of the skin as a potential reservoir for systemic exposure after
      exposure has ended was demonstrated. Especially in relation to short-term
      occupational exposures, an exposure assessment based on penetrated pesticide at
      the end of a work shift may underestimate the exposure.

PMID- 15509632
TI  - Simultaneous sampling of peroxyacetic acid and hydrogen peroxide in workplace
      atmospheres.
AB  - The use of peroxyacetic acid (PAA) in the disinfection processes in the food
      industry or for medical purposes is increasing. As it is the product of the
      reaction of acetic acid (AA) and hydrogen peroxide (HP) and coexists with them,
      and given the fact that the chemical properties of these two substances are not
      very different from PAA, the sampling and analysis of this substance in working
      atmospheres is difficult. A specific sampling device was developed. It is
      composed of: (i) a cassette with quartz fibre filters impregnated with titanium
      oxysulfate hydrate for the sampling of HP followed by; (ii) a tube filled with
      silica gel soaked with methyl p-tolylsulfoxide for the sampling of PAA. The
      analysis of this silica gel was performed by liquid chromatography with UV
      detection of the methyl p-sulfone generated by the sampling of PAA. The
      conservation of the sampling media (before and after sampling) and its efficiency
      were also checked. From the results of sampling campaigns performed in various
      workplaces, the relative contributions of PAA, AA and HP to an exposure index,
      taking into account the atmospheric concentrations and the threshold limit
      values, were established. This calculation shows that the simultaneous
      determination of PAA and HP, which the method presented in this paper allows,
      provides a fairly good estimation of the exposure.

PMID- 15509633
TI  - Inhalation and dermal exposure among asphalt paving workers.
AB  - The primary objective of this study was to identify determinants of inhalation
      and dermal exposure to polycyclic aromatic compounds (PACs) among asphalt paving
      workers. The study population included three groups of highway construction
      workers: 20 asphalt paving workers, as well as 12 millers and 6 roadside
      construction workers who did not work with hot-mix asphalt. During multiple
      consecutive work shifts, personal air samples were collected from each worker's
      breathing zone using a Teflon filter and cassette holder connected in series with
      an XAD-2 sorbent tube, while dermal patch samples were collected from the
      underside of each worker's wrist. All exposure samples were analyzed for PACs,
      pyrene and benzo[a]pyrene. Inhalation and dermal PAC exposures were highest among
      asphalt paving workers. Among paving workers, inhalation and dermal PAC exposures
      varied significantly by task, crew, recycled asphalt product (RAP) and work rate
      (inhalation only). Asphalt mix containing high RAP was associated with a 5-fold
      increase in inhalation PAC exposures and a 2-fold increase in dermal PAC
      exposure, compared with low RAP mix. The inhalation PAC exposures were consistent
      with the workers' proximity to the primary source of asphalt fume (paver
      operators > screedmen > rakers > roller operators), such that the adjusted mean
      exposures among paver operators (5.0 microg/m3, low RAP; 24 microg/m3, high RAP)
      were 12 times higher than among roller operators (0.4 microg/m3, low RAP; 2.0
      microg/m3, high RAP). The dermal PAC exposures were consistent with the degree to
      which the workers have actual contact with asphalt-contaminated surfaces (rakers
      > screedmen > paver operators > roller operators), such that the adjusted mean
      exposures among rakers (175 ng/cm2, low RAP; 417 ng/cm2, high RAP) were
      approximately 6 times higher than among roller operators (27 ng/cm2, low RAP; 65
      ng/cm2, high RAP). Paving task, RAP content and crew were also found to be
      significant determinants of inhalation and dermal exposure to pyrene. The effect
      of RAP content, as well as the fact that exposures were higher among paving
      workers than among millers and roadside construction workers, suggests that the
      PAC and pyrene exposures experienced by these paving workers were asphalt
      related.

PMID- 15509634
TI  - Nitrogen- and storage-affected carbohydrate partitioning in high-light-adapted
      Pelargonium cuttings in relation to survival and adventitious root formation
      under low light.
AB  - BACKGROUND AND AIMS: The aim of this study was to determine the role of nitrogen-
      and storage-affected carbohydrate availability in rooting of pelargonium
      cuttings, focusing on the environmental conditions of stock plant cultivation at
      low latitudes, transport of cuttings, and rooting under the low light that
      prevails during the winter rooting period in Central European greenhouses.
      METHODS: Carbohydrate partitioning in high-light-adapted cuttings of the cultivar
      'Isabell' was studied in relation to survival and adventitious root formation
      under low light. Effects of a graduated supply of mineral nitrogen to stock
      plants and of cutting storage were examined. KEY RESULTS: Nitrogen deficiency
      raised starch levels in excised cuttings, whereas the concentrations of glucose
      and total sugars in leaves and the basal stem were positively correlated with
      internal total nitrogen (Nt). Storage reduced starch to trace levels in all
      leaves, but sugar levels were only reduced in tissues of non-nitrogen deficient
      cuttings. Sugars accumulated in the leaf lamina of stored cuttings during the
      rooting period, whereas carbohydrates were simultaneously exhausted in all other
      cutting parts including the petioles, thereby promoting leaf senescence. The
      positive correlation between initial Nt and root number disappeared after
      storage. Irrespectively of storage, higher pre-rooting leaf glucose promoted
      subsequent sugar accumulation in the basal stem and final root number. The
      positive relationships between initial sugar levels in the stems with cutting
      survival and in leaves with root formation under low light were confirmed in a
      sample survey with 21 cultivars provided from different sources at low latitudes.
      CONCLUSIONS: The results indicate that adventitious rooting of pelargonium
      cuttings can be limited by the initial amount of nitrogen reserves. However, this
      relationship reveals only small plasticity and is superimposed by a predominant
      effect of carbohydrate availability that depends on the initial leaf sugar
      levels, when high-light adaptation and low current light conditions impair net
      carbon assimilation.

PMID- 15509635
TI  - Genetic abnormalities among severely oligospermic men who are candidates for
      intracytoplasmic sperm injection.
AB  - Recent reports suggest that children born after intracytoplasmic sperm injection
      performed for male factor infertility are at increased risk of congenital
      malformations and chromosome aberrations. To explain these observations, we
      hypothesized that infertile men may be more likely than fertile men to have
      genetic abnormalities. We studied 750 severely oligozoospermic men (sperm count
      <5 million/ml) who were candidates for intracytoplasmic sperm injection, and 303
      fertile men. We analyzed the peripheral blood karyotype, the Y chromosome long
      arm for detection of microdeletions in the azoospermia factors, and mutations in
      the cystic fibrosis gene and the androgen receptor gene. We also analyzed sperm
      for chromosome aneuploidies among the 421 men who subsequently entered the in
      vitro fertilization program. A total of 104 genetic abnormalities were diagnosed,
      corresponding to a frequency of 13.9% (104 of 750). Chromosomal aberrations were
      present in 5.6% (42 of 750) of infertile men and 0.3% of controls (one of 295),
      and they were in most cases alterations of the sex chromosomes. Y chromosome long
      arm microdeletions were detected in 6.0% (45 of 750) of infertile men and most
      frequently included the azoospermia factor c, whereas no cases were found in
      controls (zero of 210). Mutations in the cystic fibrosis gene were diagnosed in
      1.2% (nine of 750) of infertile men and 1.0% of controls (three of 303), and
      mutations in the androgen receptor gene were found in 1.1% (eight of 750) of
      infertile men and none of the 188 controls. Sperm sex chromosome aneuploidies
      were increased in men with karyotype anomalies and Y chromosome microdeletions as
      well as in subjects without constitutional genetic abnormalities. This study
      shows that the frequency of genetic alterations is increased among men with
      severe spermatogenic impairment. Genetic tests and genetic counseling should
      therefore be considered in oligozoospermic men who are candidates for
      intracytoplasmic sperm injection.

PMID- 15509636
TI  - Correlation between the antiinflammatory protein annexin 1 (lipocortin 1) and
      serum cortisol in subjects with normal and dysregulated adrenal function.
AB  - Annexin 1 (ANXA1), a Ca(2+) and phospholipid binding protein, is an important
      mediator of the antiinflammatory actions of glucocorticoids. However, although
      inflammatory responses in man are sensitive to alterations in adrenocortical
      function, the relationship between endogenous cortisol and ANXA1 expression has
      not been explored. Accordingly, we measured serum cortisol levels and ANXA1
      expression in peripheral blood leukocytes from subjects with normal and
      dysregulated cortisol secretion before and 30 min after a standard corticotrophin
      (ACTH) test. Our data demonstrate a highly significant correlation between the
      serum cortisol concentration and the expression of ANXA1 in neutrophils, both
      before and after ACTH treatment, and thus suggest that ANXA1 may serve as a
      marker of glucocorticoid sensitivity. They also reveal a correlation between
      ANXA1 and the serum gonadotrophins, LH and FSH, and an age-related reduction in
      ANXA1 expression in lymphocytes.

PMID- 15509637
TI  - Novel male hormonal contraceptive combinations: the hormonal and spermatogenic
      effects of testosterone and levonorgestrel combined with a 5alpha-reductase
      inhibitor or gonadotropin-releasing hormone antagonist.
AB  - We postulated that the addition of a combined types I and II, 5alpha-reductase
      inhibitor (dutasteride) or long-acting GnRH antagonist (acyline) to combination
      testosterone plus levonorgestrel treatment may be advantageous in the suppression
      of spermatogenesis for male contraception. This study aimed to examine effects of
      novel combination contraceptive regimens on serum gonadotropins and androgens and
      sperm concentration.This study was divided into three phases: screening (2 wk),
      treatment (8 wk), and recovery (4 wk). Twenty-two men (n = 5-6/group) received 8
      wk of treatment with testosterone enanthate (TE, 100 mg im weekly) combined with
      one of the following: 1) levonorgestrel (LNG) 125 mug orally daily; 2) LNG 125
      microg plus dutasteride 0.5 mg orally daily; 3) acyline 300 microg/kg sc every 2
      wk (as a comparator for any additional progestin effects); or 4) LNG 125 microg
      orally daily plus acyline 300 microg/kg sc every 2 wk. Serum gonadotropin levels
      were similarly suppressed by all treatments, falling to a nadir between 1.2 and
      3.4% and 0.5 and 0.8% baseline for FSH and LH, respectively (P < 0.05). Serum
      dihydrotestosterone levels were significantly (P < 0.05) decreased in the
      dutasteride group throughout the treatment period to a nadir of 31% baseline (wk
      7). No significant differences in sperm concentrations among treatment groups
      were seen. Severe oligospermia (0.1-3 million/ml) or azoospermia was seen in none
      of five and four of five in TE + LNG; two of six and four of six in TE + LNG +
      dutasteride; two of six and four of six in TE + acyline; and one of five and
      three of five in TE + LNG + acyline groups, respectively. There was one
      nonresponder in each of the TE + LNG and TE + LNG + acyline groups.We conclude
      that the addition of a combined types I and II, 5alpha-reductase inhibitor or
      long-acting GnRH antagonist to a testosterone plus LNG regimen provides no
      additional suppression of gonadotropins or sperm concentration over an 8-wk
      treatment period. However, further evaluation of the effects of these regimens on
      the testis (including testicular steroid levels and germ cell maturation) and the
      treatment of larger numbers of men (and for longer periods) may provide data to
      support their place in contraceptive development.

PMID- 15509638
TI  - The change in blood pressure during pubertal growth.
AB  - Blood pressure (BP) in children may increase more during puberty. Using a cohort
      of children where BP and body size had been closely monitored, we compared the
      rates of change in BP during the 3-yr period before puberty, during puberty (
      approximately 4.5-yr period), and the 3-yr period after puberty. Because there
      was no specific staging information with respect to puberty, we used pubertal
      growth (PG) as a surrogate of puberty. The latter was determined from serial
      measurements of height. All subjects (n = 151) were followed from before the
      period of PG to the period after PG; none were related. An age-dependent increase
      in systolic BP in the pre-PG period was similar regardless of sex or race. During
      PG, systolic BP in males increased three to six times faster than in the pre-PG
      period. In females, systolic BP increased less than in males during PG but still
      increased two to four times faster than in the pre-PG period. The increase in
      males was significantly greater than in females (P < 0.001). Post-PG changes in
      BP were similar to changes in pre-PG BP. In summary, PG was associated with
      profound increases in systolic BP. There were noticeably greater increments in
      males than in females consistent with the emergence of the well known sexual
      dimorphism in BP.

PMID- 15509639
TI  - Coexistence of intracellular and membrane-bound progesterone receptors in human
      testis.
AB  - Progesterone and progesterone receptors (PR) play a crucial role in female
      reproduction, but their roles in male reproductive physiology are largely
      unknown. Our previous studies demonstrated the presence of a specific membrane
      bound PR in mature human spermatozoa that is known to regulate important sperm
      functions. The present study was undertaken to determine whether there exist PR
      in human testis and to investigate their molecular characteristics and expression
      profiles. PR mRNA and protein were detected in the spermatogenic cells, Sertoli
      cells, and occasionally the Leydig cells. PR protein was localized in nucleus and
      cytoplasm of spermatogonia, primary and secondary spermatocytes, and round
      spermatids in a stage-specific manner. Intense PR localization was observed in
      stages IV and V, whereas it was low at stages I, II, and III of spermatogenesis.
      RT-PCR studies revealed the presence of transcripts for PR in human testis and
      spermatogenic cells. In accordance with the reported molecular sizes of the known
      isoforms of PR, two mRNA transcripts of 3.8 and 2.8 kb for PR in adult human
      testis and spermatogenic cell RNA were detected by Northern blot hybridization.
      Western blot analysis of testicular and spermatogenic cell lysates revealed two
      bands of 120 and 90 kDa, corresponding to the conventional PR. In these tissue
      lysates, an additional band of approximately 55 kDa was detected that was also
      observed as a single band in sperm lysates, indicating that this smaller protein
      may correspond to the membrane-bound PR. The membrane-bound PR protein was
      demonstrated on the spermatogenic cells when probed with progesterone-bound
      fluorescein conjugate. The results of the present study demonstrate the existence
      of both intracellular PR-B and PR-A mRNA and protein in the spermatogenic cells
      of the human testis. A membrane-bound PR was also localized in these cells. The
      varying levels of intracellular PR during different stages of spermatogenesis and
      the presence of the membrane-bound PR imply the significance of progesterone in
      male reproductive events such as regulation of spermatogenesis.

PMID- 15509640
TI  - [18F]fluorodeoxyglucose uptake in recurrent thyroid cancer is related to
      hexokinase i expression in the primary tumor.
AB  - Patients suspected of recurrent differentiated thyroid cancer (DTC) may require
      "blind" (131)I therapy, with the disadvantage of unpredictable efficacy and
      toxicity. Alternatively, positron emission tomography (PET) with
      [(18)F]fluorodeoxyglucose ((18)FDG) can document the recurrence, thereby
      rationalizing therapeutic options. This study compared (18)FDG uptake in vivo
      with biomarkers expected to be involved in the underlying biological mechanisms.
      Additionally, we investigated whether such features were present in the primary
      tumors. Preoperatively, 19 patients with recurrent DTC underwent PET. (18)FDG
      uptake was compared with histological and immunohistochemical features in
      surgical specimens of recurrent and primary tumor. Thirteen of 19 recurrences
      were positive at PET, and (18)FDG uptake was associated with the expression of
      hexokinase type I (HK I; P = 0.011). All lesions with HK I overexpression were
      positive on (18)FDG PET. HK I expression in the original primary tumor and the
      metastases was similar in 82% (rho = 0.648; P = 0.005). In suspected recurrent
      thyroid cancer, stratification for (18)FDG PET may benefit from pretest
      immunohistochemical analysis of HK I of the primary tumor, as HK I negativity
      indicates a low likelihood of PET positivity.

PMID- 15509641
TI  - Associations of sex-hormone-binding globulin (SHBG) with non-SHBG-bound levels of
      testosterone and estradiol in independently living men.
AB  - Results of in vitro experiments indicate that with increasing concentrations of
      SHBG, testosterone (T) is preferentially bound to SHBG in comparison with
      estradiol (E2). In these studies, the ratio of non-SHBG-bound E2 (non-SHBG-E2) to
      non-SHBG-T increased with increasing levels of SHBG. SHBG has consequently been
      regarded as an estrogen amplifier. In this cross-sectional study in 399 men aged
      between 40 and 80 yr we tested whether higher levels of SHBG are associated with
      a higher estrogen/androgen ratio in vivo. The mean T level of these men was in
      the eugonadal range [536 +/- 152 ng/dl (18.6 +/- 5.26 nmol/liter), mean +/- sd].
      With increasing SHBG levels the non-SHBG-bound fraction of T decreased from 80 to
      36% and that of E2 from 89 to 53%. Higher levels of SHBG were associated with
      higher levels of both total T [regression coefficient (beta) after adjustment for
      age and body mass index, 286 +/- 15.8; P < 0.001] and total E2 (beta = 4.47 +/-
      0.90; P < 0.001). However, SHBG levels were negatively related with levels of non
      SHBG-E2 (beta = -1.78 +/- 0.69; P < 0.001), whereas there was a positive
      association between levels of SHBG and non-SHBG-T (beta = 32.0 +/- 9.78; P =
      0.001). Furthermore, we observed a negative relationship between SHBG levels and
      the E2/T ratio of either total (beta = -0.016 +/- 0.002; P < 0.001) or non-SHBG
      bound (beta = -0.011 +/- 0.002; P < 0.001) hormone. Therefore, we conclude that
      in eugonadal men, higher SHBG levels are associated with lower levels of non-SHBG
      E2 but slightly higher levels of non-SHBG-T. This means that SHBG cannot be
      regarded as an estrogen amplifier in eugonadal men.

PMID- 15509642
TI  - Evidence for the presence of toll-like receptor 4 system in the human
      endometrium.
AB  - We investigated whether Toll-like receptor (TLR) 4 is at work in the human
      endometrium. The expression of TLR4 mRNA in endometrial epithelial cells (EECs)
      and stromal cells (ESCs) was detected by RT-PCR and in situ hybridization.
      Western blotting analysis revealed the TLR4 protein expression in both cell
      populations. Treatment of lipopolysaccharide (LPS), the actions of which are
      mediated through TLR4, significantly increased IL-8 secretion from cultured ESCs
      in a dose-dependent fashion. The stimulatory effect of LPS was inhibited by the
      addition of neutralizing antibodies for TLR4 and CD14. LPS also stimulated
      nuclear translocation of nuclear factor-kappaB in ESCs, which was also inhibited
      by these antibodies. On the other hand, LPS did not stimulate IL-8 secretion in
      cultured EECs. However, LPS stimulated IL-8 secretion from EECs in the presence
      of soluble CD14. Flow cytometric analysis revealed that CD14 was expressed on the
      cell surface of ESCs but not EECs. In addition, immunohistochemical analysis
      showed that CD14 was stained in ESCs but not EECs. Pretreatment of interferon
      gamma (IFN-gamma) enhanced LPS-induced IL-8 secretion from ESCs. IFN-gamma
      increased the expression of TLR4 mRNA. It also increased the amounts of mRNA for
      CD14, MD2, and MyD88, which are needed for LPS recognition in concert with TLR4.
      In summary, we demonstrated that both ESCs and EECs express TLR4 and respond to
      LPS through TLR4. We further showed that EECs, not ESCs, required soluble CD14
      for TLR4 activation. Interestingly, IFN-gamma, an antiinfectious cytokine, was
      found to activate the TLR4 system in ESCs. Altogether, the results imply that the
      TLR4 system might represent local immunity in the human endometrium with
      differential modes of TLR4 actions between ESCs and EECs.

PMID- 15509643
TI  - Free rather than total circulating insulin-like growth factor-I determines the
      feedback on growth hormone release in normal subjects.
AB  - Pituitary GH secretion is feedback regulated by circulating IGF-I. However, it
      remains to be determined whether the feedback control is mediated through
      circulating free or total IGF-I. To study this, we compared the temporal changes
      in circulating levels of GH vs. free and total IGF-I during fasting. Seventeen
      healthy normal-weight subjects (body mass index 23.4 +/- 0.6 kg/m(2)) were
      studied during 80 h of fasting. Serum was assayed for GH every 3 h; total, free,
      and bioactive IGF-I, IGF binding protein (IGFBP)-1, -2, and -3 as well as IGFBP-1
      bound IGF-I were assayed every morning. During fasting, mean 24-h GH levels
      increased from 1.41 +/- 0.20 to 3.01 +/- 0.46 and 2.09 +/- 0.30 microg/liter (d 1
      vs. d 2 and 3; P < 0.03). After 24 h of fasting, free and bioactive IGF-I had
      decreased by 40 +/- 5 and 17 +/- 5%, respectively (P < 0.02), and both
      concentrations remained suppressed for the rest of the study. In contrast, total
      IGF-I remained unchanged until the end of d 3, at which levels were slightly
      reduced (P < 0.007). IGFBP-1 increased from 38 +/- 2 to 137 +/- 24, 212 +/- 32,
      and 214 +/- 22 microg/liter (d 1 vs. d 2, d 3, and end of d 3; P < 0.0001), and
      these changes closely paralleled those of IGFBP-1-bound IGF-I (P < 0.0001). IGFBP
      2 increased only transiently at d 2 (P < 0.05), and IGFBP-3 remained unchanged.
      The increase in mean 24-h GH levels from d 1 to d 2 correlated inversely with the
      relative reduction in free IGF-I from d 1 to d 2 (r = -0.51; P = 0.04), i.e. the
      larger the reduction in free IGF-I, the larger the increase in GH. None of the
      other IGF-related parameters correlated with GH. In conclusion, the temporal
      relationship between the increase in GH and the reduction in free IGF-I supports
      the hypothesis that circulating free IGF-I mediates the feedback regulation of GH
      secretion.

PMID- 15509644
TI  - Inflammation, insulin resistance, and glucose intolerance in acute myocardial
      infarction patients without a previous diagnosis of diabetes mellitus.
AB  - We examined the prevalence of impaired glucose metabolism and its association
      with inflammation and insulin resistance (IR) in acute myocardial infarction
      (AMI) patients without a previous diagnosis of diabetes. This prospective study
      enrolled 52 AMI patients, and 75-g oral glucose tolerance testing was performed
      on 30 patients at discharge and again 3 months later. We also measured serum
      adiponectin, high sensitive C-reactive protein, and IL-6 on both occasions. Data
      were compared with those of 30 type 2 diabetic patients without a history of AMI.
      Forty percent and 36.7% of AMI patients had impaired glucose tolerance (IGT) at
      discharge and at 3 months, respectively. The corresponding proportions for newly
      diagnosed diabetes are 33.0% and 30.0%. At discharge, AMI patients with IGT or
      diabetes showed higher high sensitive C-reactive protein and IL-6 levels compared
      with AMI patients with normal glucose tolerance or control type 2 diabetic
      patients. Furthermore, AMI patients with IGT or diabetes exhibited higher IR and
      lower serum adiponectin levels than AMI patients with normal glucose tolerance at
      3 months after discharge. Previously undiagnosed diabetes and IGT are common in
      Korean patients with AMI. These glycometabolic abnormalities are associated with
      inflammation, IR, and serum adiponectin levels.

PMID- 15509645
TI  - Glucocorticoids decrease thyrotropin-releasing hormone messenger ribonucleic acid
      expression in the paraventricular nucleus of the human hypothalamus.
AB  - The way glucocorticoids affect TRH mRNA expression in the paraventricular nucleus
      of the hypothalamus is still unclear. In view of its relevance for Cushing's
      syndrome and depression, we measured TRH mRNA expression in human hypothalami
      obtained at autopsy by means of quantitative TRH mRNA in situ hybridization. In
      corticosteroid-treated subjects (n = 10), TRH mRNA hybridization signal was
      decreased as compared with matched control subjects (n = 10) (Mann-Whitney U
      test, P = 0.02). By inference, hypercortisolism as present in patients with
      Cushing's syndrome or major depression may contribute to lower serum TSH or
      symptoms of depression by lowering hypothalamic TRH expression.

PMID- 15509646
TI  - Hemorrhagic pheochromocytoma associated with systemic corticosteroid therapy and
      presenting as myocardial infarction with severe hypertension.
AB  - Pheochromocytomas classically present with paroxysms of hypertension and
      adrenergic symptoms including headaches, palpitations, tremor, and anxiety.
      However, these tumors can be clinically silent and occasionally present only when
      catecholamine release is up-regulated by exogenous stimuli. In addition, the
      clinical presentation of pheochromocytoma can mimic a number of more common
      medical conditions, including migraine headaches, cardiac arrhythmias, and
      myocardial infarction, making diagnosis difficult. In this report, we present the
      case of a young woman who, while receiving oral corticosteroid therapy for
      presumed migraine headaches, suffered a myocardial infarction and ultimately
      hemorrhaged into a previously undiagnosed pheochromocytoma. Our patient exhibited
      severe, labile hypertension after the administration of iv beta-blockade for
      presumed myocardial ischemia, raising our initial clinical suspicion for
      pheochromocytoma. In this paper we review some of the key clinical issues related
      to this complex case, including steroid-induced stimulation of catecholamine
      synthesis and release, the role of pheochromocytoma in myocardial ischemia and
      electrocardiographic changes, and the rare complication of tumor hemorrhage. We
      then briefly review the essential diagnostic and management strategies for this
      rare but potentially lethal tumor, with specific emphasis on pheochromocytoma
      related cardiovascular emergencies and the surgical management of tumor
      hemorrhage.

PMID- 15509647
TI  - Electroporation loading of calcium-sensitive dyes into the CNS.
AB  - Calcium imaging of neural network function has been limited by the extent of
      tissue labeled or the time taken for labeling. We now describe the use of
      electroporation-an established technique for transfecting cells with genes-to
      load neurons with calcium-sensitive dyes in the isolated spinal cord of the
      neonatal mouse in vitro. The dyes were injected subdurally, intravascularly, or
      into the central canal. This technique results in rapid and extensive labeling of
      neurons and their processes at all depths of the spinal cord, over a rostrocaudal
      extent determined by the position and size of the electrodes. Our results suggest
      that vascular distribution of the dye is involved in all three types of
      injections. Electroporation disrupts local reflex and network function only
      transiently (approximately 1 h), after which time they recover. We describe
      applications of the method to image activity of neuronal populations and
      individual neurons during antidromic, reflex, and locomotor-like behaviors. We
      show that these different motor behaviors are characterized by distinct patterns
      of activation among the labeled populations of cells.

PMID- 15509648
TI  - Akt activation is necessary for growth factor-induced trafficking of functional
      K(Ca) channels in developing parasympathetic neurons.
AB  - The protein kinase Akt is a crucial regulator of neuronal survival and apoptosis.
      Here we show that Akt activation is necessary for mobilization of large
      conductance K(Ca) channels in ciliary ganglion (CG) neurons evoked by beta
      neuregulin-1 (NRG1) and transforming growth factor-beta1 (TGFbeta1). Application
      of NRG1 to embryonic day 9 (E9) CG neurons increased Akt phosphorylation, as
      observed previously for TGF(beta)1. NRG1- and TGF(beta)1-evoked stimulation of
      K(Ca) is blocked by inhibitors of PI3K by overexpression of a dominant-negative
      form of Akt, by overexpression of CTMP, an endogenous negative regulator of Akt,
      and by application of the Akt inhibitor 1L-6-hydroxymethyl-chiro-inositol 2-(R)-2
      O-methyl-3-O-octadecylcarbonate (HIMO). Conversely, overexpression of a
      constitutively-active form of Akt was sufficient by itself to increase
      mobilization of functional K(Ca) channels. NRG1 and TGF(beta)1 evoked an Akt
      dependent increase in cell-surface SLO alpha-subunits. These procedures have no
      effect on voltage-activated Ca2+ currents. Thus Akt plays an essential role in
      the developmental regulation of excitability in CG neurons.

PMID- 15509649
TI  - OPA1 requires mitofusin 1 to promote mitochondrial fusion.
AB  - The regulated equilibrium between mitochondrial fusion and fission is essential
      to maintain integrity of the organelle. Mechanisms of mitochondrial fusion are
      largely uncharacterized in mammalian cells. It is unclear whether OPA1, a dynamin
      related protein of the inner membrane mutated in autosomal dominant optic
      atrophy, participates in fusion or fission. OPA1 promoted the formation of a
      branched network of elongated mitochondria, requiring the integrity of both its
      GTPase and C-terminal coiled-coil domain. Stable reduction of OPA1 levels by RNA
      interference resulted in small, fragmented, and scattered mitochondria. Levels of
      OPA1 did not affect mitochondrial docking, but they correlated with the extent of
      fusion as measured by polyethylene glycol mitochondrial fusion assays. A genetic
      analysis proved that OPA1 was unable to tubulate and fuse mitochondria lacking
      the outer membrane mitofusin 1 but not mitofusin 2. Our data show that OPA1
      functionally requires mitofusin 1 to regulate mitochondrial fusion and reveal a
      specific functional difference between mitofusin 1 and 2.

PMID- 15509651
TI  - Cajal bodies, nucleoli, and speckles in the Xenopus oocyte nucleus have a low
      density, sponge-like structure.
AB  - Nuclear organelles, unlike many cytoplasmic organelles, lack investing membranes
      and are thus in direct contact with the surrounding nucleoplasm. Because the
      properties of the nucleoplasm and nuclear organelles influence the exchange of
      molecules from one compartment to another, it is important to understand their
      physical structure. We studied the density of the nucleoplasm and the density and
      permeability of nucleoli, Cajal bodies (CBs), and speckles in the Xenopus oocyte
      nucleus or germinal vesicle (GV). Refractive indices were measured by
      interferometry within intact GVs isolated in oil. The refractive indices were
      used to estimate protein concentrations for nucleoplasm (0.106 g/cm3), CBs (0.136
      g/cm3), speckles (0.162 g/cm3), and the dense fibrillar region of nucleoli (0.215
      g/cm3). We determined similar protein concentrations for nuclear organelles
      isolated in aqueous media, where they are no longer surrounded by nucleoplasm. To
      examine the permeability of nuclear organelles, we injected fluorescent dextrans
      of various molecular masses (3-2000 kDa) into the cytoplasm or directly into the
      GV and measured the extent to which they penetrated the organelles. Together, the
      interferometry and dextran penetration data show that organelles in the Xenopus
      GV have a low-density, sponge-like structure that provides access to
      macromolecules from the nucleoplasm.

PMID- 15509650
TI  - Regulation of endocytosis, nuclear translocation, and signaling of fibroblast
      growth factor receptor 1 by E-cadherin.
AB  - Fibroblast growth factor (FGF) receptors (FGFRs) signal to modulate diverse
      cellular functions, including epithelial cell morphogenesis. In epithelial cells,
      E-cadherin plays a key role in cell-cell adhesion, and its function can be
      regulated through endocytic trafficking. In this study, we investigated the
      location, trafficking, and function of FGFR1 and E-cadherin and report a novel
      mechanism, based on endocytic trafficking, for the coregulation of E-cadherin and
      signaling from FGFR1. FGF induces the internalization of surface FGFR1 and
      surface E-cadherin, followed by nuclear translocation of FGFR1. The
      internalization of both proteins is regulated by common endocytic machinery,
      resulting in cointernalization of FGFR1 and E-cadherin into early endosomes. By
      blocking endocytosis, we show that this is a requisite, initial step for the
      nuclear translocation of FGFR1. Overexpression of E-cadherin blocks both the
      coendocytosis of E-cadherin and FGFR1, the nuclear translocation of FGFR1 and FGF
      induced signaling to the mitogen-activated protein kinase pathway. Furthermore,
      stabilization of surface adhesive E-cadherin, by overexpressing p120ctn, also
      blocks internalization and nuclear translocation of FGFR1. These data reveal that
      conjoint endocytosis and trafficking is a novel mechanism for the coregulation of
      E-cadherin and FGFR1 during cell signaling and morphogenesis.

PMID- 15509652
TI  - Critical role of collapsin response mediator protein-associated molecule CRAM for
      filopodia and growth cone development in neurons.
AB  - Collapsin response mediator proteins (CRMPs) have been implicated in signaling of
      axonal guidance, including semaphorins. We have previously identified a unique
      member of this gene family, CRMP-associated molecule CRAM (CRMP-5), which is
      phylogenetically divergent from the other four CRMPs. In this study, we have
      examined the distribution and function of CRAM in developing neurons.
      Immunohistochemical analysis showed accumulation of CRAM in the filopodia of
      growth cones. Experiments using cytochalasin D indicated that filopodial
      localization of CRAM was independent of filamentous actin. Overexpression of CRAM
      in neuronal cells significantly promoted filopodial growth and led to the
      formation of supernumerary growth cones, which acquired resistance to semaphorin
      3A stimulation. Finally, knockdown of CRAM by using RNA interference blocked
      filopodial formation and revealed an aberrant morphology of growth cones. We
      propose that CRAM regulates filopodial dynamics and growth cone development,
      thereby restricting the response of growth cone to repulsive guidance cues.

PMID- 15509653
TI  - Phylogenetic analysis of the formin homology 2 domain.
AB  - Formin proteins are key regulators of eukaryotic actin filament assembly and
      elongation, and many species possess multiple formin isoforms. A nomenclature
      system based on fundamental features would be desirable, to aid the rapid
      identification and characterization of novel formins. In this article, we attempt
      to systematize the formin family by performing phylogenetic analyses of the
      formin homology 2 (FH2) domain, an independently folding region common to all
      formins, which alone can influence actin dynamics. Through database searches, we
      identify 101 FH2 domains from 26 eukaryotic species, including 15 in mice.
      Sequence alignments reveal a highly conserved yeast-specific insert in the "knob
      loop" region of the FH2 domain, with unknown functional consequences.
      Phylogenetic analysis using minimum evolution (ME), maximum parsimony (MP), and
      maximum likelihood (ML) algorithms strongly supports the existence of seven
      metazoan groups. Yeast FH2 domains segregate from all other eukaryotes, including
      metazoans, other fungi, plants, and protists. Sequence comparisons of non-FH2
      regions support relationships between three metazoan groups (Dia, DAAM, and FRL)
      and examine previously identified coiled-coil and Diaphanous auto-regulatory
      domain sequences. This analysis allows for a formin nomenclature system based on
      sequence relationships, as well as suggesting strategies for the determination of
      biochemical and cellular activities of these proteins.

PMID- 15509654
TI  - Genetic and environmental factors influencing glutathione homeostasis in
      Saccharomyces cerevisiae.
AB  - Glutathione is an essential metabolite protecting cells against oxidative stress
      and aging. Here, we show that endogenously synthesized glutathione undergoes
      intercellular cycling during growth to stationary phase. Genome-wide screening
      identified approximately 270 yeast deletion mutants that overexcrete glutathione,
      predominantly in the reduced form, and identified a surprising set of functions
      important for glutathione homeostasis. The highest excretors were affected in
      late endosome/vacuolar functions. Other functions identified included
      nitrogen/carbon source signaling, mitochondrial electron transport,
      ubiquitin/proteasomal processes, transcriptional regulation, ion transport and
      the cellular integrity pathway. For many mutants the availability of branched
      chain amino acids and extracellular pH influenced both glutathione homeostasis
      and cell viability. For all mutants tested, the onset of glutathione excretion
      occurred when intracellular concentration exceeded the maximal level found in the
      parental strain; however, in some mutants prolonged excretion led to substantial
      depletion of intracellular glutathione. These results significantly contribute to
      understanding mechanisms affecting glutathione homeostasis in eukaryotes and may
      provide insight into the underlying cause of glutathione depletion in
      degenerative processes such as Parkinson's disease. The important implications of
      these data for use of the yeast deletion collection for the study of other
      phenomena also are discussed.

PMID- 15509655
TI  - Cellular distribution and functions of wild-type and constitutively activated
      Dictyostelium PakB.
AB  - Dictyostelium PakB, previously termed myosin I heavy chain kinase, is a member of
      the p21-activated kinase (PAK) family. Two-hybrid assays showed that PakB
      interacts with Dictyostelium Rac1a/b/c, RacA (a RhoBTB protein), RacB, RacC, and
      RacF1. Wild-type PakB displayed a cytosolic distribution with a modest enrichment
      at the leading edge of migrating cells and at macropinocytic and phagocytic cups,
      sites consistent with a role in activating myosin I. PakB fused at the N terminus
      to green fluorescent protein was proteolyzed in cells, resulting in removal of
      the catalytic domain. C-terminal truncated PakB and activated PakB lacking the
      p21-binding domain strongly localized to the cell cortex, to macropinocytic cups,
      to the posterior of migrating cells, and to the cleavage furrow of dividing
      cells. These data indicate that in its open, active state, the N terminus of PakB
      forms a tight association with cortical actin filaments. PakB-null cells
      displayed no significant behavioral defects, but cells expressing activated PakB
      were unable to complete cytokinesis when grown in suspension and exhibited
      increased rates of phagocytosis and pinocytosis.

PMID- 15509656
TI  - A small C-terminal sequence of Aurora B is responsible for localization and
      function.
AB  - Aurora B, a protein kinase required in mitosis, localizes to inner centromeres at
      metaphase and the spindle midzone in anaphase and is required for proper
      chromosome segregation and cytokinesis. Aurora A, a paralogue of Aurora B,
      localizes instead to centrosomes and spindle microtubules. Except for distinct N
      termini, Aurora B and Aurora A have highly similar sequences. We have combined
      small interfering RNA (siRNA) ablation of Aurora B with overexpression of
      truncation mutants to investigate the role of Aurora B sequence in its function.
      Reintroduction of Aurora B during siRNA treatment restored its localization and
      function. This permitted a restoration of function test to determine the sequence
      requirements for Aurora B targeting and function. Using this rescue protocol,
      neither N-terminal truncation of Aurora B unique sequence nor substitution with
      Aurora A N-terminal sequence affected Aurora B localization or function.
      Truncation of unique Aurora B C-terminal sequence from terminal residue 344 to
      residue 333 was without effect, but truncation to 326 abolished localization and
      function. Deletion of residues 326-333 completely abolished localization and
      blocked cells at prometaphase, establishing this sequence as critical to Aurora B
      function. Our findings thus establish a small sequence as essential for the
      distinct localization and function of Aurora B.

PMID- 15509658
TI  - ApoE-mediated cholesterol efflux from macrophages: separation of autocrine and
      paracrine effects.
AB  - Macrophages in the vessel wall secrete high levels of apolipoprotein E (apoE).
      Cholesterol efflux from macrophages to apoE has been shown to decrease foam cell
      formation and prevent atherosclerosis. An apoE molecule can mediate cholesterol
      efflux from the macrophage that originally secreted it (autocrine effect) or from
      surrounding macrophages (paracrine effect). Traditional methodologies have not
      been able to separate these serial effects. The novel methodology presented here
      was developed to separate autocrine and paracrine effects by using a simple
      mathematical model to interpret the effects of dilution on apoE-mediated
      cholesterol efflux. Our results show that, at very dilute concentrations, the
      paracrine effect of apoE is not evident and the autocrine effect becomes the
      dominant mediator of efflux. However, at saturating concentrations, paracrine
      apoE causes 80-90% of the apoE-mediated cholesterol efflux, whereas autocrine
      apoE is responsible for the remaining 10-20%. These results suggest that the
      relative importance of autocrine and paracrine apoE depends on the size of the
      local distribution volume, a factor not considered in previous in vitro studies
      of apoE function. Furthermore, autocrine effects of apoE could be critical in the
      prevention of foam cell formation in vivo. This novel methodology may be
      applicable to other types of mixed autocrine/paracrine systems, such as signal
      transduction systems.

PMID- 15509657
TI  - Insulin-like growth factor I controls adhesion strength mediated by alpha5beta1
      integrins in motile carcinoma cells.
AB  - One of the intriguing questions regarding cell motility concerns the mechanism
      that makes stationary cells move. Here, we provide the first physical evidence
      that the onset of breast cancer cell motility in response to insulin-like growth
      factor I (IGF-I) correlates with lowering of adhesion strength from 2.52 +/- 0.20
      to 1.52 +/- 0.13 microdynes/microm2 in cells attached to fibronectin via
      alpha5beta1 integrin. The adhesion strength depends on the dose of IGF-I and time
      of IGF-I treatment. Weakening of cell-matrix adhesion is blocked significantly (p
      < 0.01) by the catalytically inactive IGF-I receptor (IGF-IR) and the
      phosphoinositide 3-kinase (PI-3 kinase) inhibitor LY-294002, but it is unaffected
      by mitogen-activated protein kinase kinase inhibitor UO-126 and Src kinase
      inhibitor PP2. Sustained blockade of Rho-associated kinase (ROCK) with Y-27632
      down-regulates adhesion strength in stationary, but not in IGF-I-treated, cells.
      Jasplakinolide, a drug that prevents actin filament disassembly, counteracts the
      effect of IGF-I on integrin-mediated cell adhesion. In the absence of growth
      factor signaling, ROCK supports a strong adhesion via alpha5beta1 integrin,
      whereas activation of the IGF-IR kinase reduces cell-matrix adhesion through a PI
      3K-dependent, but ROCK-independent, mechanism. We propose that disassembly of the
      actin filaments via PI-3 kinase pathway contributes to weakening of adhesion
      strength and induction of cell movement. Understanding how cell adhesion and
      migration are coordinated has an important application in cancer research,
      developmental biology, and tissue bioengineering.

PMID- 15509659
TI  - Arg333 and Arg334 in the COOH terminus of the human P2Y1 receptor are crucial for
      Gq coupling.
AB  - The P2Y(1) ADP receptor activates G(q) and causes increases in intracellular
      Ca(2+) concentration through stimulation of PLC. In this study, we investigated
      the role of the amino acid residues in the COOH terminus of the human P2Y(1)
      receptor in G(q) activation. Stimulation of Chinese hamster ovary (CHO-K1) cells
      stably expressing the wild-type human P2Y(1) receptor (P2Y(1)-WT cells), P2Y(1)
      DeltaR340-L373, or P2Y(1)-DeltaD356-L373 with 2-methylthio-ADP (2-MeSADP) caused
      inositol phosphate production. In contrast, cells expressing P2Y(1)-DeltaT330
      L373, a mutant lacking the entire COOH terminus, completely lost their response
      to 2-MeSADP. Similar data were obtained by using these cell lines and measuring
      Ca(2+) mobilization upon stimulation with 2-MeSADP, indicating that the 10 amino
      acids (330TFRRRLSRAT339) in the COOH terminus of the human P2Y(1) receptor are
      essential for G(q) coupling. Radioligand binding demonstrated that both the
      P2Y(1)-WT and P2Y(1)-DeltaT330-L373-expressing cells have almost equal binding of
      [(3)H]MRS2279, a P2Y(1) receptor antagonist, indicating that COOH-terminal
      truncation did not drastically affect the conformation of the receptor. CHO-K1
      cells expressing a chimeric P2Y(12) receptor with the P2Y(1) COOH terminus failed
      to elicit G(q) functional responses, indicating that the P2Y(1) COOH terminus is
      essential but not sufficient for G(q) activation. Finally, cells expressing a
      double-mutant P2Y(1) receptor (R333A/R334A) in the conserved BBXXB region of the
      COOH terminus of the G(q)-activating P2Y receptors completely lost their
      functional ability to activate G(q). We conclude that the two arginine residues
      (R333R334) in the COOH terminus of the human P2Y(1) receptor are essential for
      G(q) coupling.

PMID- 15509660
TI  - Heat shock protein 20-mediated force suppression in forskolin-relaxed swine
      carotid artery.
AB  - Increases in cyclic nucleotide levels induce smooth muscle relaxation by
      deactivation [reductions in myosin regulatory light chain (MRLC) phosphorylation
      (e.g., by reduced [Ca(2+)])] or force suppression (reduction in force without
      reduction in MRLC phosphorylation). Ser(16)-heat shock protein 20 (HSP20)
      phosphorylation is the proposed mediator of force suppression. We evaluated three
      potential hypotheses whereby Ser(16)-HSP20 phosphorylation could regulate smooth
      muscle force: 1) a threshold level of HSP20 phosphorylation could inactivate a
      thin filament as a whole, 2) phosphorylation of a single HSP20 could fully
      inactivate a small region of a thin filament, or 3) HSP20 phosphorylation could
      weakly inhibit myosin binding at either the thin- or thick-filament level. We
      tested these hypotheses by analyzing the dependence of force on Ser(16)-HSP20
      phosphorylation in swine carotid media. First, we determined that swine HSP20 has
      a second phosphorylation site at Ser(157). Ser(157)-HSP20 phosphorylation values
      were high and did not change during contractile activation or forskolin-induced
      relaxation. Forskolin significantly increased Ser(16)-HSP20 phosphorylation. The
      relationship between Ser(16)-HSP20 phosphorylation and force remained linear and
      was shifted downward in partially activated muscles relaxed with forskolin.
      Neither forskolin nor nitroglycerin induced actin depolymerization as detected
      using the F/G-actin ratio method in smooth muscle homogenates. These results
      suggest that force suppression does not occur in accordance with the first
      hypothesis (inactivation of a thin filament as a whole). Our data are more
      consistent with the second and third hypotheses that force suppression is
      mediated by full or partial inhibition of local myosin binding at the thin- or
      thick-filament level.

PMID- 15509661
TI  - MAPK signaling regulates endothelial cell assembly into networks and expression
      of MT1-MMP and MMP-2.
AB  - Microvascular endothelial cells embedded within three-dimensional (3D) type I
      collagen matrixes assemble into cellular networks, a process that requires the
      upregulation of membrane type 1 (MT1) matrix metalloproteinase (MMP) and MMP-2.
      The purpose of this study was to identify the signaling pathways responsible for
      the transcriptional activation of MT1-MMP and MMP-2 in endothelial cells in 3D
      collagen lattices. We hypothesized that the 3D type I collagen induction of MT1
      MMP and MMP-2 is mediated by the mitogen-activated protein kinase family of
      enzymes. Here, we show that 3D type I collagen elicits a persistent increase in
      ERK1/2 and JNK activation and a decrease in p38 activation. Inhibition of ERK1/2
      or JNK disrupted endothelial network formation in 3D type I collagen lattices,
      whereas inhibition of p38 promoted network formation. mRNA levels of both MT1-MMP
      and MMP-2 were attenuated by ERK1/2 inhibition but unaffected by either JNK or
      p38 inhibition. By contrast, expression of constitutively active MEK was
      sufficient to stimulate MMP-2 production in a monolayer of endothelial cells
      cultured on type I collagen. These results provide evidence that signaling
      through both ERK1/2 and JNK regulates endothelial assembly into cellular networks
      but that the ERK1/2 signaling cascade specifically regulates network formation
      and the production of both MT1-MMP and MMP-2 genes in response to 3D type I
      collagen.

PMID- 15509662
TI  - Development of an oral exposure mouse model to predict drug-induced
      hypersensitivity reactions by using reporter antigens.
AB  - The capability of certain drugs to cause immune-mediated drug hypersensitivity
      reactions in susceptible individuals has initiated a search for pre-clinical
      screening tools to identify immunosensitizing drugs. Since most drugs are taken
      orally, hazard assessment of their immunosensitizing potential should include
      oral exposure models. In this study, the predictive value of the reporter antigen
      (RA) approach was investigated in combination with oral or intraperitoneal (ip)
      exposure to a selection of allergenic drugs, i.e., D-penicillamine (D-Pen),
      Diclofenac (DF), or Nevirapine (Nevi). The RA trinitrophenyl-Ovalbumin (TNP-OVA)
      was used to assess the capacity of the drugs to stimulate systemic immune
      responses to a bystander antigen, whereas the RA TNP-Ficoll was used to indicate
      whether the drugs were able to induce specific anamnestic T-cell responses. TNP
      OVA was injected (ip) in C3H/HeOuJ mice that were subsequently exposed (orally or
      ip) to one of the drugs via different exposure protocols. All three model drugs
      used resulted in delayed type hypersensitivity reactions to TNP-OVA after ip and
      oral exposure. In addition, TNP-specific serum antibody levels were increased
      after ip exposure to Nevi, and after both oral and ip exposure to D-Pen and DF.
      These data indicate that the present drugs are able to stimulate immune responses
      to bystander antigens. Responses to TNP-Ficoll were measured in the popliteal
      lymph node of BALB/c mice three weeks after they received a single oral dose of D
      Pen or DF. Results of this approach show that orally pre-treated mice responded
      with enhanced responses (TNP-specific IgG1 and IFN-gamma production) to sub
      optimal doses of D-Pen or DF in a drug-specific manner. Data with TNP-Ficoll
      indicate that these drugs stimulate systemic formation of specific T cells.
      Together, the RA-approach allows assessment of systemic sensitization upon oral
      and/or ip exposure to the selected drugs. To further evaluate the utility of
      these models, more drugs, including non-allergenic drugs and those that require
      metabolic conversion to become allergenic need to be studied in the present
      models.

PMID- 15509663
TI  - Xenobiotics inhibit hepatic uptake and biliary excretion of taurocholate in rat
      hepatocytes.
AB  - Reports suggest that troglitazone, and to a lesser extent bosentan, may alter
      bile acid homeostasis by inhibiting the bile salt export pump. The present
      studies examined the hypothesis that these xenobiotics may modulate multiple
      hepatic bile acid transport mechanisms. In suspended rat hepatocytes,
      troglitazone (10 microM) decreased the initial rate of taurocholate uptake
      approximately 3-fold; the initial uptake rate of estradiol-17beta-D-glucuronide,
      a substrate of the organic anion transporting polypeptides, also was decreased
      approximately 4-fold. Bosentan (100 microM) decreased the initial uptake rate of
      taurocholate and estradiol-17beta-D-glucuronide by approximately 12- and
      approximately 7-fold, respectively. In sandwich-cultured rat hepatocytes, 10-min
      accumulation of taurocholate in cells + bile canaliculi (408 +/- 57 pmol/mg
      protein) was decreased significantly by troglitazone (157 +/- 17 pmol/mg protein,
      respectively) only in the presence of Na+, the driving force for the sodium
      taurocholate cotransporting polypeptide. A similar decrease with 10-fold higher
      concentrations of bosentan was noted. The biliary excretion index of taurocholate
      (55 +/- 8%) was decreased in the presence of 10 microM troglitazone (27 +/- 2%)
      and 100 microM bosentan (10 +/- 6%). In conclusion, xenobiotics may alter hepatic
      bile acid transport by inhibiting both hepatic uptake and biliary excretion.

PMID- 15509664
TI  - Downregulation of lysyl oxidase and upregulation of cellular thiols in rat fetal
      lung fibroblasts treated with cigarette smoke condensate.
AB  - Lysyl oxidase (LO), a copper-dependent enzyme, plays a critical role in the
      formation and repair of the extracellular matrix (ECM) by catalyzing the
      crosslinking of elastin and collagen. To better understand mechanisms of
      cigarette smoke (CS)-induced emphysema, we examined changes in LO and its
      substrates, i.e., elastin and collagen type I, the major components of cellular
      thiols, i.e., metallothionein (MT) and glutathione (GSH), and gamma
      glutamylcysteine synthetase (gamma-GCS), a key enzyme for GSH biosynthesis, in
      cigarette smoke condensate (CSC)-treated rat fetal lung fibroblasts (RFL6).
      Exposure of RFL6 cells to CSC decreased levels of LO catalytic activity, mRNA,
      and protein, i.e., the 46 kDa preproenzyme, the 50 kDa proenzyme and the 32 kDa
      mature enzyme in a dose-dependent manner. In addition, CSC also inhibited the
      expression of collagen type I and elastin, substrates of LO and important
      components of the lung ECM. Meanwhile, cellular thiols including MT and GSH as
      well as gamma-GCS were markedly upregulated in CSC-treated cells. To evaluate
      modulation of LO expression by cellular thiols, we further examined the effect of
      increased levels of GSH on LO expression at protein and catalytic levels.
      Interestingly, exposure of cells to glutathione monoethyl ester, a GSH delivery
      system, effectively elevated cellular GSH levels and induced a dose-dependent
      decrease in levels of the protein species and catalytic activity of LO. These
      results suggest that upregulation by CSC of cellular thiols may play an important
      role in the downregulation of LO and subsequently destabilization of the lung ECM
      in CS-induced emphysema.

PMID- 15509665
TI  - Toxicokinetics of BDE 47 in female mice: effect of dose, route of exposure, and
      time.
AB  - 2,2',4,4'-Tetrabromodiphenyl ether (BDE 47) is present in commercial mixtures of
      polybrominated diphenyl ethers (PBDEs), which are used as flame retardants in a
      wide variety of consumer products. Despite its small contribution to PBDE global
      production and usage, BDE 47 is the major congener found in environmental samples
      and human tissue. No human data are currently available regarding the
      toxicokinetics of BDE 47 either as an individual congener or in the commercial
      mixture. Because previous studies have suggested potential toxicokinetic
      differences between rodent species, this study was conducted in an effort to
      fully characterize absorption, distribution, and excretion parameters following a
      single dose with respect to dose, time, and route of exposure in female C57BL/6
      mice. Over 80% of the administered dose was absorbed after oral or intratracheal
      administration, whereas approximately 62% was absorbed when the dose was applied
      dermally. Disposition was dictated by lipophilicity as adipose and skin were
      major depot tissues. BDE 47 was rapidly excreted in the urine and feces. Of
      particular interest was the amount of parent compound found in the urine, which
      was a major factor in determining an initial whole-body half life of 1.5 days
      after a single oral exposure. Elimination, both whole-body and from individual
      tissues, was biphasic. Initial half-lives were 1-3 days, whereas terminal half
      lives were much longer, suggesting the potential for bioaccumulation. This
      toxicokinetic behavior has important implications for extrapolation of
      toxicological studies to the assessment of health risk in humans.

PMID- 15509666
TI  - PBPK model for radioactive iodide and perchlorate kinetics and perchlorate
      induced inhibition of iodide uptake in humans.
AB  - Detection of perchlorate (ClO4-) in several drinking water sources across the
      U.S. has lead to public concern over health effects from chronic low-level
      exposures. Perchlorate inhibits thyroid iodide (I-) uptake at the sodium (Na+)
      iodide (I-) symporter (NIS), thereby disrupting the initial stage of thyroid
      hormone synthesis. A physiologically based pharmacokinetic (PBPK) model was
      developed to describe the kinetics and distribution of both radioactive I- and
      cold ClO4- in healthy adult humans and simulates the subsequent inhibition of
      thyroid uptake of radioactive I- by ClO4-. The model successfully predicts the
      measured levels of serum and urinary ClO4- from drinking water exposures, ranging
      from 0.007 to 12 mg ClO4-/kg/day, as well as the subsequent inhibition of thyroid
      131I- uptake. Thyroid iodine, as well as total, free, and protein-bound
      radioactive I- in serum from various tracer studies, are also successfully
      simulated. This model's parameters, in conjunction with corresponding model
      parameters established for the male, gestational, and lactating rat, can be used
      to estimate parameters in a pregnant or lactating human, that have not been or
      cannot be easily measured to extrapolate dose metrics and correlate observed
      effects in perchlorate toxicity studies to other human life stages. For example,
      by applying the adult male rat:adult human ratios of model parameters to those
      parameters established for the gestational and lactating rat, we can derive a
      reasonable estimate of corresponding parameters for a gestating or lactating
      human female. Although thyroid hormones and their regulatory feedback are not
      incorporated in the model structure, the model's successful prediction of free
      and bound radioactive I- and perchlorate's interaction with free radioactive I-
      provide a basis for extending the structure to address the complex hypothalamic
      pituitary-thyroid feedback system. In this paper, bound radioactive I- refers to
      I- incorporated into thyroid hormones or iodinated proteins, which may or may not
      be bound to plasma proteins.

PMID- 15509667
TI  - Gingival carcinogenicity in female Harlan Sprague-Dawley rats following two-year
      oral treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin and dioxin-like
      compounds.
AB  - We evaluated gingival toxicities induced by chronic exposure of female Harlan
      Sprague-Dawley rats to dioxin and dioxin-like compounds (DLCs) and compared them
      to similarly induced oral lesions reported in the literature. This investigation
      represents part of an ongoing initiative of the National Toxicology Program to
      determine the relative potency of chronic toxicity and carcinogenicity of
      polychlorinated dioxins, furans, and biphenyls. For two years, animals were
      administered by gavage 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); 3,3',4,4',5
      pentachlorobiphenyl (PCB126); 2,3,4,7,8-pentachlorodibenzofuran (PeCDF);
      2,2',4,4',5,5'-hexachlorobiphenyl (PCB153); a tertiary mixture of TCDD, PCB126,
      and PeCDF; a binary mixture of PCB126 and 153; or a binary mixture of PCB126 and
      2,3',4,4',5-pentachlorobiphenyl (PCB118); control animals received corn oil
      acetone vehicle (99:1) alone. A full complement of tissues, including the palate
      with teeth, was examined microscopically. In the groups treated with TCDD and the
      mixtures of TCDD, PCB126, and PeCDF; PCB126 and 153; and PCB126 and 118, the
      incidences of gingival squamous hyperplasia increased significantly. Moreover, in
      the groups treated with TCDD, PCB126, and the mixture of PCB126 and 153, squamous
      cell carcinoma (SCC) in the oral cavity increased significantly. This
      investigation constitutes the first report documenting that chronic
      administration of dioxin-like PCBs can induce gingival SCC in rats. These results
      indicate that dioxin and DLCs target the gingiva of the oral cavity, in
      particular the junctional epithelium of molars.

PMID- 15509668
TI  - Novel progestogenic activity of environmental endocrine disruptors in the
      upregulation of calbindin-D9k in an immature mouse model.
AB  - Endocrine disruption is a major global health concern in the industrialized
      world. The induction of uterine calbindin-D9k (CaBP-9k), which belongs to a large
      family of intracellular calcium binding proteins, was used to assess the exposure
      of endocrine disruptors (EDs) in an immature mouse model. Sex steroid hormones
      have been demonstrated to regulate uterine CaBP-9k expression in the uterus of
      rats and mice. In particular, the mouse CaBP-9k gene was predominantly regulated
      by progesterone (P4), whereas rat CaBP-9k was mainly induced by 17-beta-estradiol
      (E2) in the uterus. In the present study, immature (14-day-old) female mice were
      injected with 4-tert-octylphenol (OP), nonylphenol (NP), bisphenol A (BPA), E2,
      or P4 to determine their effects on uterine CaBP-9k mRNA and protein expression.
      In addition, to specify estrogenic or progestogenic activity of EDs in the
      regulation of CaBP-9k, the mice were co-treated with ICI 182,780, an estrogen
      receptor (ER) antagonist, or RU486, a progesterone receptor (PR) antagonist,.
      Treatments with OP, NP, or BPA resulted in an increase in CaBP-9k mRNA and
      protein in the uterus of immature mice in a dose-dependent and time-dependent
      manner. The EDs-induced expression of CaBP-9k mRNA and protein was reversed or
      abolished by pretreatment with RU486 or ICI 182,780, suggesting that these
      synthetic chemicals may have both progestogenic and estrogenic properties by
      acting through PR or ER in the induction of uterine CaBP-9k mRNA and protein in
      this model. These results describe a novel in vivo model for detection of both
      estrogenic and progestogenic activities of EDs in the induction of CaBP-9k mRNA
      and protein in the uterus of immature mice.

PMID- 15509669
TI  - Modeling and predicting stress-induced immunosuppression in mice using blood
      parameters.
AB  - Previous studies have shown that the area under the corticosterone concentration
      vs. time curve (AUC) can be used to model and predict the effects of restraint
      stress and chemical stressors on a variety of immunological parameters in the
      mouse spleen and thymus. In order to complete a risk assessment parallelogram,
      similar data are needed with blood as the source of immune system cells, because
      this is the only tissue routinely available from human subjects. Therefore,
      studies were conducted using treatments for which the corticosterone AUC values
      are already known: exogenous corticosterone, restraint, propanil, atrazine, and
      ethanol. Immunological parameters were measured using peripheral blood from mice
      treated with a series of dosages of each of these agents. Flow cytometry was used
      to quantify MHC II, B220, CD4, and CD8 cells. Leukocyte and differential counts
      were done. Spleen cell number and NK cell activity were evaluated to confirm
      similarity to previous studies. Immune parameter data from mouse blood indicate
      that MHC II expression has consistent quantitative relationships to
      corticosterone AUC values, similar to but less consistent than those observed in
      the spleen. Other immune parameters tended to have greater variability in the
      blood than in the spleen. The pattern observed in the spleen in which the
      chemical stressors generally produced very similar effects as noted for restraint
      stress (at the same corticosterone AUC values) was not observed for blood
      leukocytes. Nevertheless, MHC class II expression seems to provide a reasonably
      consistent indication of stress exposure in blood and spleen.

PMID- 15509670
TI  - My approach to atypical melanocytic lesions.
AB  - Histological assessment of melanocytic naevi constitutes a substantial proportion
      of a dermatopathologist's daily workload. Although they may be excised for
      cosmetic reasons, most lesions encountered are clinically atypical and are
      biopsied or excised to exclude melanoma. Although dysplastic naevi are most often
      encountered, cytological atypia may be a feature of several other melanocytic
      lesions, including genital type naevi, acral naevi, recurrent naevi, and neonatal
      or childhood naevi. With greater emphasis being given to cosmetic results, and
      because of an ever increasing workload, several "quicker and less traumatising"
      techniques have been introduced in the treatment and diagnosis of atypical naevi
      including punch, shave, and scoop shave biopsies. A major limitation to all of
      these alternatives is that often only part of the lesion is available for
      histological assessment and therefore all too frequently the pathologist's report
      includes a recommendation for complete excision so that the residual lesion can
      be studied. Complete or large excision of all clinically atypical naevi permits
      histological assessment of the entire lesion, and in most cases spares the
      patient the need for further surgical intervention.

PMID- 15509671
TI  - Warfarin reversal.
AB  - Warfarin is the most commonly used oral anticoagulant in the UK. It is associated
      with few side effects apart from haemorrhage. The most appropriate way to reverse
      the anticoagulant effect of warfarin depends on the clinical circumstances. In
      serious bleeding, rapid reversal is required, whereas in minor bleeding or
      asymptomatic over anticoagulation, a more leisurely approach is usually
      appropriate. This review discusses the current approaches to warfarin reversal in
      clinical practice. The development of a uniform approach to warfarin reversal in
      the Northern Region is described.

PMID- 15509672
TI  - Use of tissue microarray for interlaboratory validation of HER2
      immunocytochemical and FISH testing.
AB  - AIMS: To evaluate the use of tissue microarray (TMA) technology as a validation
      tool for HER2 testing by both immunocytochemistry (ICC) and fluorescence in situ
      hybridisation (FISH) in the diagnostic setting. METHODS: TMA constructs from 57
      cases of breast cancer were evaluated for HER2 (by ICC and FISH) by two centres.
      The results were compared. RESULTS: There was a high level of concordance for
      both ICC and FISH. In five "discrepant" cases only three would have had a
      potential impact on patient management. CONCLUSIONS: Validation of HER2 analysis
      in the clinical setting by ICC and FISH is essential. The use of TMAs provides
      for an economy of scale and would be practical in the setting of interlaboratory
      and intralaboratory validation. It is suggested that routine HER2 ICC and FISH
      should continue to be performed in laboratories on whole sections. Following
      this, TMAs would be constructed for all cases of breast cancer. ICC and FISH
      would be performed on these to validate the results. The TMAs would be available
      for circulation to other centres for validation purposes. The standardisation of
      testing between centres, the potential difficulty of minimum case numbers, and
      the workload issues surrounding validation would all be facilitated by this
      approach.

PMID- 15509673
TI  - Non-specific multiple ulcers of the small intestine unrelated to non-steroidal
      anti-inflammatory drugs.
AB  - AIM: Non-steroidal anti-inflammatory drug (NSAID) enteropathy is a cause of
      chronic blood and protein loss from the intestine. The aim of this investigation
      was to compare NSAID enteropathy with enteropathy not related to chronic NSAID
      use. PATIENTS/METHODS: During the period 1967-97, 12 cases of non-specific small
      intestinal multiple ulcers were laparotomised because of chronic and persistent
      blood loss for a prolonged period. The clinical features before and after
      surgery, and the small intestinal lesions, were compared between NSAID users and
      non-users. RESULTS: Three patients were NSAID users and the other nine were not.
      Initial clinical manifestations, haemoglobin concentrations, serum protein
      values, and inflammatory reactions were similar in the two groups. In both groups
      there were multicentric stenoses in the small intestine. In those not using
      NSAIDs, the stenoses were accompanied by multiple, sharply demarcated small
      ulcers with minimal and non-specific chronic inflammatory infiltrates. The small
      intestinal ulcers in NSAID users showed linear and circumferential alignment.
      NSAID users were free from medication during the subsequent period of
      observation, whereas repeated laparotomy and medication were required in eight of
      the nine patients not using NSAIDs. CONCLUSION: There appears to be a chronic
      enteropathy, not related to the use of NSAIDs, in which non-specific multiple
      ulcers are found. This enteropathy may be a distinct entity that causes
      persistent blood and protein loss from the intestine.

PMID- 15509674
TI  - Tenascin C expression is upregulated in pancreatic cancer and correlates with
      differentiation.
AB  - BACKGROUND: Tenascin C is a large, hexameric, extracellular matrix protein that
      is present during embryonic development but essentially absent in adult tissues.
      It is involved in remodelling processes, such as wound healing and tumour
      development. Tissue expression of tenascin C correlates with prognosis in
      colorectal, cervical, and breast cancer and in carcinoma of the papilla of Vater.
      AIM: To study the expression of tenascin C in pancreatic cancer and to compare
      the staining results with the patients' clinicopathological data. MATERIAL AND
      METHODS: Formalin fixed, paraffin wax embedded specimens from 146 patients with
      pancreatic adenocarcinoma were stained with an anti-tenascin C monoclonal
      antibody. RESULTS: Tenascin C immunoreactivity was seen in most samples of
      pancreatic carcinoma: staining was weak in 72 (49%), moderate in 52 (36%), strong
      in 10 (7%), and negative in 12 (8%) samples. Tenascin C expression correlated
      with age (< or = 66 v >66 years) and poor differentiation (grades 1-2 v 3). There
      was no correlation between tenascin C expression and survival, clinical stage,
      tumour size, nodal status, distant metastasis, tumour location, or sex.
      CONCLUSION: Tenascin C expression was increased in most pancreatic carcinomas,
      but contrary to the results in other cancers, it is not a prognostic factor in
      pancreatic cancer.

PMID- 15509675
TI  - The metabolic marker tumour pyruvate kinase type M2 (tumour M2-PK) shows
      increased expression along the metaplasia-dysplasia-adenocarcinoma sequence in
      Barrett's oesophagus.
AB  - BACKGROUND: Proliferating and tumour cells express the glycolytic isoenzyme,
      pyruvate kinase type M2 (M2-PK). In tumours cells, M2-PK usually exists in
      dimeric form (tumour M2-PK), causing the accumulation of glycolytic
      phosphometabolites, which allows cells to invade areas with low oxygen and
      glucose concentrations. AIMS: To investigate the expression of tumour M2-PK
      during the metaplasia-dysplasia-adenocarcinoma sequence of Barrett's oesophagus,
      and to assess the prognostic usefulness of tumour M2-PK in oesophageal cancer.
      MATERIALS/METHODS: One hundred and ninety cases selected from the histopathology
      archives as follows: 17 reflux oesophagitis, 37 Barrett's oesophagus, 21 high
      grade dysplasia, 112 adenocarcinomas, and three control tumours. Sections were
      stained immunohistochemically with antibody to tumour M2-PK. RESULTS: Tumour M2
      PK was expressed in all cases, and increased cytoplasmic expression was seen with
      progression along the metaplasia-dysplasia-adenocarcinoma sequence. All cases of
      adenocarcinoma showed 100% staining so that tumour M2-PK was not a useful
      prognostic marker. CONCLUSIONS: Tumour M2-PK is not a specific marker of
      Barrett's adenocarcinoma, but may be important as a marker of transformed and
      highly proliferating clones during progression along the metaplasia-dysplasia
      adenocarcinoma sequence.

PMID- 15509676
TI  - ALCAM/CD166 is overexpressed in colorectal carcinoma and correlates with
      shortened patient survival.
AB  - BACKGROUND: Activated leucocyte cell adhesion molecule (ALCAM) has been
      implicated in tumorigenesis and tumour progression of malignant melanoma and
      prostate cancer. AIMS: To clarify the expression patterns of ALCAM in colon
      cancer and to correlate these with clinicopathological parameters, including
      patient survival. METHODS: One hundred and eleven colorectal carcinomas were
      immunostained for ALCAM (clone MOG/07) using a standard detection system.
      Cytoplasmic and membranous immunoreactivity were scored semiquantitatively.
      Fisher's exact test, chi2 test for trends, Kaplan-Meier analysis, and Cox's
      regression were applied. RESULTS: In colorectal cancer, 58.6% and 30.6% of cases
      showed strong cytoplasmic and membranous expression of ALCAM, respectively. No
      significant correlation with patient age, tumour grade, stage, or nodal status
      was apparent. In survival analyses, membranous ALCAM expression correlated
      significantly (Cox's regression, p=0.028; relative risk, 2.3) with shortened
      patient survival. CONCLUSIONS: ALCAM is frequently upregulated in colorectal
      cancer and is a new independent prognostic marker, underscoring the importance of
      ALCAM in tumour progression in this disease.

PMID- 15509677
TI  - Histopathological assessment of lymph nodes in colorectal carcinoma: does triple
      levelling detect significantly more metastases?
AB  - AIMS: Standard practice is to take one section from every lymph node found in
      colorectal carcinoma resection specimens, to look for metastatic carcinoma. This
      study evaluates whether assessing three sections separated by 100 microm detects
      significantly more metastases in nodes than the conventional single section.
      METHODS: A retrospective study of 100 colorectal carcinoma resection specimens.
      All blocks containing lymph nodes had two extra histological sections cut
      (separated by 100 microm) and stained with haematoxylin and eosin. The original
      slide was called level 1, and the extra two sections levels 2 and 3. RESULTS:
      Twenty Dukes's A (equivalent to WHO-UICC stage grouping I, pTNM stage pT1/2N0),
      43 Dukes's B (equivalent to WHO-UICC stage grouping II, pTNM stage pT3/4N0), and
      37 Dukes's C (equivalent to WHO-UICC stage grouping III, pTNM stage at least pN1)
      cases were examined (total 1453 nodes). Twelve extra metastases (in 11 patients)
      were discovered in nodes at levels 2 and 3, which were negative in level 1. Ten
      cases were Dukes's C and, in one patient, this led to upstaging from N1 to N2
      (pTNM classification system). One case was Dukes's B and the discovery of a
      single metastasis on level 2 upstaged it to Dukes's C. CONCLUSIONS: Triple
      levelling detected more tumour deposits than the conventional single section. In
      two patients, the staging classification of the lesion was changed, with
      potentially important implications for prognosis and management.

PMID- 15509678
TI  - Deficient alpha smooth muscle actin expression as a cause of intestinal pseudo
      obstruction: fact or fiction?
AB  - AIMS: To test the hypothesis that deficient alpha smooth muscle actin (ASMA)
      expression in intestinal smooth muscle, as assessed by immunohistochemistry, is
      specifically associated with clinical evidence of intestinal pseudo-obstruction.
      METHODS: Seventeen archival, formalin fixed, paraffin wax embedded samples of
      small intestine and 12 samples of large intestine were studied. Two of the small
      bowel samples and one large bowel sample were from patients with symptoms of
      intestinal pseudo-obstruction. The controls were longitudinal surgical margins
      from hemicolectomies performed for carcinoma. Immunohistochemistry was performed
      using primary antibodies to ASMA, smooth muscle myosin heavy chain (SMMHC), and
      desmin. The relative intensities of immunohistochemical expression in the
      circular and longitudinal muscle layers of the muscularis propria were assessed
      in each sample, for all three markers. RESULTS: All samples showed strong SMMHC
      and desmin expression in the inner circular and outer longitudinal layers of the
      muscularis propria. Both small intestinal samples from the cases and 11 of 15
      controls showed no or minimal ASMA expression in the inner circular layer, with
      the remaining four controls also showing ASMA labelling in this layer that was
      weaker than within the longitudinal muscle. In contrast, intense ASMA expression
      was seen in both muscle layers within the large intestine in the remaining case,
      and in the controls. CONCLUSIONS: There is insufficient evidence from this study
      to support the hypothesis that ASMA deficiency in intestinal smooth muscle, as
      determined by immunohistochemistry on archival tissues, is specifically
      associated with intestinal pseudo-obstruction.

PMID- 15509679
TI  - Recurrent chromosomal imbalances and structurally abnormal breakpoints within
      complex karyotypes of malignant peripheral nerve sheath tumour and malignant
      triton tumour: a cytogenetic and molecular cytogenetic study.
AB  - BACKGROUND: Cytogenetic studies of malignant peripheral nerve sheath tumours
      (MPNSTs) and malignant triton tumours (MTTs) are rare. AIMS: To undertake
      cytogenetic analysis of these tumours. METHODS: Conventional cytogenetic analysis
      of 21 MPNSTs and MTTs from 17 patients (nine with peripheral neurofibromatosis
      (NF1)) was carried out using standard culture and harvesting procedures. For a
      more precise identification of composite structural rearrangements and marker
      chromosomes, spectral karyotypic analysis (SKY) was applied to a subset of cases.
      In addition, EGFR gene copy number was assessed by fluorescence in situ
      hybridisation (FISH) analysis in a subset of cases. RESULTS: Cytogenetic analysis
      revealed predominantly complex karyotypes. SKY analysis was useful in further
      defining many structural anomalies. Structural aberrations most frequently
      involved chromosomal bands or regions 1p31-36, 4q28-35, 7p22, 11q22-23, 19q13,
      20q13, and 22q11-13. Overall, loss of chromosomal material was much more common
      than gain. Loss of chromosomes or chromosomal regions 1p36 (48%), 3p21-pter
      (52%), 9p23-pter (57%), 10 (48%), 11q23-qter (48%), 16/16q24 (62%), 17(43%), and
      22/22q (48%), and gains of 7/7q (29%) and 8/8q (29%) were most prominent. These
      gains and losses were distributed equally between MPNST and MTT, demonstrating
      that these entities are similar with respect to recurrent genomic imbalances.
      Similarly, none of the recurrent chromosomal breakpoints or imbalances was
      restricted to either NF1 associated or sporadic MPNSTs. FISH analysis was
      negative for amplification. CONCLUSIONS: These cytogenetic and molecular
      cytogenetic findings expand the knowledge of chromosomal alterations in MPNST and
      MTT, and point to possible recurring regions of interest.

PMID- 15509680
TI  - Expression of ATM, p53, and the MRE11-Rad50-NBS1 complex in myoepithelial cells
      from benign and malignant proliferations of the breast.
AB  - AIMS: To analyse the expression of proteins involved in DNA double strand break
      detection and repair in the luminal and myoepithelial compartments of benign
      breast lesions and malignant breast tumours with myoepithelial differentiation.
      METHODS: Expression of the ataxia telangiectasia (ATM) and p53 proteins was
      immunohistochemically evaluated in 18 benign and malignant myoepithelial tumours
      of the breast. Fifteen benign breast lesions with prominent myoepithelial
      compartment were also evaluated for these proteins, in addition to those in the
      MRE11-Rad50-NBS1 (MRN) complex, and the expression profiles were compared with
      those seen in eight independent non-cancer (normal breast) samples and in the
      surrounding normal tissues of the benign and malignant tumours examined. RESULTS:
      ATM expression was higher in the myoepithelial compartment of three of 15 benign
      breast lesions and lower in the luminal compartment of eight of these lesions
      compared with that found in the corresponding normal tissue compartments.
      Malignant myoepithelial tumours overexpressed ATM in one of 18 cases. p53 was
      consistently negative in benign lesions and was overexpressed in eight of 18
      malignant tumours. In benign breast lesions, expression of the MRN complex was
      significantly more reduced in myoepithelial cells (up to 73%) than in luminal
      cells (up to 40%) (p=0.0005). CONCLUSIONS: Malignant myoepithelial tumours rarely
      overexpress ATM but are frequently positive for p53. In benign breast lesions,
      expression of the MRN complex was more frequently reduced in the myoepithelial
      than in the luminal epithelial compartment, suggesting different DNA repair
      capabilities in these two cell types.

PMID- 15509681
TI  - Molecular strain identification of the Mycobacterium tuberculosis complex in
      archival tissue samples.
AB  - AIMS: To investigate the use of different molecular analyses that can identify
      distinct strains of human pathogenic mycobacteria in formalin fixed and paraffin
      wax embedded archival tissue samples to see whether it is possible to
      differentiate between the members of the Mycobacterium tuberculosis complex (M
      tuberculosis, M bovis, M africanum, M microti, or M canettii) and/or substrains
      in a high number of samples. This would be of interest for identifying individual
      infection traits and superinfection by different mycobacterial strains. METHODS:
      Forty nine archival tissue samples with clinically and/or histologically
      suspected tuberculosis infection were subjected to molecular DNA analysis.
      RESULTS: The molecular analysis revealed the presence of M tuberculosis complex
      DNA in 20 samples, whereas acid fast bacilli could be detected by Ziehl-Neelsen
      staining in only eight samples. All IS6110 positive samples were further
      characterised by spoligotyping and seven cases provided M tuberculosis specific
      signatures, whereas M bovis specific signatures were obtained in four cases. The
      analysis of mtp40, oxyR, and pncA partial gene sequences confirmed the presence
      of M tuberculosis in six cases and M bovis in one case. The amplification and
      sequencing of four further genetic regions (katG, gyrA, TbD1, RD9) characterised
      six "modern" M tuberculosis strains belonging to genetic groups 2 or 3.
      CONCLUSION: This study provides clear evidence that archival paraffin wax
      embedded material can be used for further studies on the strain identification of
      M tuberculosis complex strains and can therefore unequivocally be used for the
      study of the epidemiology and evolution of tuberculosis pathogens.

PMID- 15509682
TI  - Serological speciation of human schistosome infections by ELISA with a panel of
      three antigens.
AB  - AIMS: To find out whether serology can reliably speciate human schistosomiasis
      using a simple enzyme linked immunosorbent assay (ELISA) technique. METHODS:
      Stored sera from 66 patients with microscopically confirmed schistosomiasis were
      subjected to ELISA using a panel of three antigens, namely: unfractionated
      Schistosoma mansoni soluble egg antigen (SEA); CEF6, a cationic fraction of SEA;
      and crude S margrebowiei egg antigen, prepared from an animal schistosome closely
      related to S haematobium. RESULTS: The optical densities (ODs) obtained using
      CEF6 as antigen were significantly higher in sera from S mansoni infected
      patients than in sera from S haematobium infected patients (median OD, 0.810 v
      0.595). Using S margrebowiei egg antigen, the optical densities were
      significantly higher in S haematobium sera than in S mansoni sera (median OD,
      0.794 v 0.544). There was no significant difference in optical densities between
      S mansoni and S haematobium sera using SEA (median OD, 0.725 v 0.737). The ratio
      of ODs (CEF6 to S margrebowiei egg antigen) was calculated: a ratio of >1
      indicated S mansoni infection (sensitivity, 88%) and a ratio of <1 indicated S
      haematobium infection (sensitivity, 84%). The odds ratio for S haematobium having
      an OD ratio of <1 was 36.8 (95% confidence interval, 7.0 to 194). CONCLUSIONS:
      The identity of the infecting species of schistosome can be determined using the
      panel of antigens described. SEA should be used to screen serum samples, and the
      CEF6 : S margrebowiei egg antigen ELISA optical density ratio can be used where
      serological speciation is required.

PMID- 15509684
TI  - Extracutaneous infantile haemangioma is also Glut1 positive.
AB  - AIM: To investigate whether extracutaneous infantile haemangioma-like tumours are
      immunohistochemically similar to cutaneous infantile haemangiomas. METHODS:
      Mammary, salivary gland, liver (one each), and placental (two cases) capillary
      haemangiomas and typical examples of cutaneous (eight cases) infantile
      haemangioma were investigated immunohistochemically for alpha smooth muscle actin
      and Glut1, a proposed marker for the skin localised lesion. Positive internal
      controls included red blood cells, perineurium, trophoblast, and endothelial
      cells of the placental capillaries. Extralesional vessel endothelium acted as a
      negative control (except in the placenta). The liver haemangioma and both
      chorioangiomas presented in patients with Beckwith-Wiedemann syndrome. RESULTS:
      The endothelial cells of all the vascular lesions were Glut1 positive. These were
      consistently surrounded by a rim of alpha smooth muscle actin positive pericytic
      cells. Controls reacted appropriately. CONCLUSIONS: All infantile haemangiomas
      were immunohistochemically positive for Glut1: expression of this molecule was
      not limited to infantile haemangiomas of the skin. These tumours comprise
      proliferations of both endothelial and pericytic cells. The association with
      Beckwith-Wiedemann syndrome may provide a clue to the molecular genetics of
      infantile haemangioma.

PMID- 15509685
TI  - Karyometry detects subvisual differences in chromatin organisation state between
      non-recurrent and recurrent papillary urothelial neoplasms of low malignant
      potential.
AB  - AIM: To analyse nuclear chromatin texture in non-recurrent and recurrent
      papillary urothelial neoplasms of low malignant potential (PUNLMPs). MATERIALS:
      Ninety three karyometric features were analysed on haematoxylin and eosin stained
      sections from 20 PUNLMP cases: 10 from patients with a solitary PUNLMP lesion,
      who were disease free during at least eight years' follow up, and 10 from
      patients with unifocal PUNLMP, one or more recurrences being seen during follow
      up. RESULTS: Kruskal-Wallis analysis was used to search for features showing
      significant differences between recurrent and non-recurrent cases. Significance
      was better than p<0.005 for more than 20 features. Based on significance, six
      texture features were selected for discriminant analysis. Stepwise linear
      discriminant analysis reduced Wilk's lambda to 0.87, indicating a highly
      significant difference between the two multivariate data sets, but only modest
      ability to discriminate (70% correct case classification). A box sequential
      classifier was used based on data derived from discriminant analysis. The
      classifier took three classification steps and classified 19 of the 20 cases
      correctly (95% correct case classification). To determine whether significant
      case grouping could also be obtained based on an objective criterion, the merged
      data sets of non-recurrent and recurrent cases were submitted to the unsupervised
      learning algorithm P-index. Two clusters were formed with significant
      differences. The subsequent application of a Cooley/Lohnes classifier resulted in
      an overall correct case classification rate of 85%. CONCLUSIONS: Karyometry and
      multivariate analyses detect subvisual differences in chromatin organisation
      state between non-recurrent and recurrent PUNLMPs, thus allowing identification
      of lesions that do or do not recur.

PMID- 15509686
TI  - Cost efficiency analysis of modern cytocentrifugation methods versus liquid based
      (Cytyc Thinprep) processing of urinary samples.
AB  - BACKGROUND/AIMS: Liquid based cytology (LBC) was developed as a replacement for
      cytocentrifugation in the treatment of cell suspensions. Because accurate data
      comparing the quality and total cost of modern cytocentrifugation methods versus
      LBC in non-gynaecological samples are not available, this study was designed to
      investigate these issues. METHODS: The study comprised 224 urine samples treated
      with the Thermo Shandon Cytospin 4 using reusable TPX chambers, disposable
      Cytofunnels for samples up to 0.5 ml, and disposable Megafunnels for samples up
      to 6 ml. Each method was compared with the Cytyc Thinprep processing of a paired
      sample. Quality was assessed by scoring cellularity, fixation, red blood cells,
      leucocytes, abnormalities of urothelial cells, and suitability for molecular
      studies. Wage costs, investment, and consumables allowed a "total cost" to be
      calculated on the basis of 200 specimens/month. Total cost and quality combined
      were used to calculate an index of total quality (ITQ). RESULTS:
      Cytocentrifugation with disposable chambers resulted in a global quality superior
      to that of Cytyc Thinprep LBC. Preparation and screening times were 2.25 and 1.33
      2 times greater when using LBC compared with cytocentrifugation. The total cost
      each month reached 1960.23 $ to 2833.43 $ for cytocentrifugation methods and
      5464.95 $ for Cytyc Thinprep LBC (92.8-178.8% increased cost). ITQ of
      cytocentrifugation with disposable chambers surpassed that of Cytyc Thinprep LBC
      (37.25/32.08 and 9.98, respectively). CONCLUSION: Cytyc Thinprep LBC and
      cytocentrifugation are both appropriate methods for cytology based molecular
      studies, but cytocentrifugation remains the quality standard for current
      treatment of urinary samples because of its lower cost.

PMID- 15509687
TI  - WHO reclassification of breast lymphomas.
AB  - Fourteen cases of breast lymphoma, identified from hospital records between 1990
      and 2004, were reclassified according to the World Health Organisation criteria.
      Primary cases occurred more frequently and all cases were of B cell origin,
      predominantly involving the right breast. Most primary cases were diffuse large B
      cell lymphomas, whereas secondary cases were heterogeneous in type and most had a
      poor prognosis.

PMID- 15509688
TI  - Gastric duplication in an adult mimicking mucinous cystadenoma of the pancreas.
AB  - Gastric duplication cyst (GDC) in an adult can have several clinical
      presentations. A review of the literature showed previously reported cases of GDC
      presenting as pancreatic pseudocyst or with greatly raised concentrations of
      carbohydrate antigen 19-9 (CA 19-9). It is often difficult to discriminate GDC
      from pancreatic cystic tumour, in particular pancreatic mucinous cystadenoma, in
      which concentrations of carcinoembryonic antigen and CA 19-9 are classically
      raised. This report describes an adult case of GDC mimicking a mucinous
      cystadenoma of the pancreas. This is the first report of a simultaneous increase
      in carcinoembryonic antigen and CA 19-9 in GDC in the absence of malignancy.
      Although few cases of carcinoma arising from a GDC having been reported, the
      production of oncofetal antigens raises the problem of a precancerous condition
      in long standing intestinal duplications. In this situation surgical resection
      must be performed.

PMID- 15509689
TI  - Serrated adenoma of the duodenum.
AB  - The duodenum is the most common site for extracolonic adenomas in patients with
      familial adenomatous polyposis (FAP). These adenomas are usually tubular,
      villous, or tubulovillous. This report describes a patient with FAP who had a
      duodenal adenoma with a different histology--it had the microscopic attributes of
      a serrated adenoma--tumours that are relatively common in the colorectal mucosa
      and are occasionally found in the stomach. A 78 year old man with FAP and
      multiple adenomas was colectomised and the rectum amputated. Several years later
      he developed silent jaundice. The surgical specimen showed an adenomatous growth
      juxtaposing the papilla of Vater. The adenoma had epithelial fronds with
      crenated, sawtooth-like configurations caused by scalloped epithelial infolding.
      The nuclei covering the notched fronds were pleomorphic, stratified, either cigar
      shaped with irregular chromatin deposits or vesicular shaped with a large
      nucleolus. One area showed involvement of a duct by neoplastic epithelium with
      extension into periluminal glands. No invasive carcinoma was present. Serrated
      adenomas differ from tubular and villous adenomas in their histological
      organisation and their initial pattern of cell proliferation and genotypic
      aberration. Increased awareness of the existence of serrated neoplasms in the
      duodenum may result in similar cases being reported in the future.

PMID- 15509690
TI  - Lymphocytic gastritis-like T cell lymphoma: molecular evidence of an unusual
      recurrence.
AB  - This report describes a patient with a gastric biopsy specimen showing
      histomorphological and immunohistochemical appearances indistinguishable from
      those usually present in lymphocytic gastritis, a rare condition of unknown
      aetiology with a distinctive phenotype. The patient had a history of a biopsy
      confirmed T cell non-Hodgkin lymphoma at two anatomical sites (bladder and
      stomach), which was subsequently treated. Molecular analysis of the T cell
      receptor (TCR) gamma chain gene rearrangements showed a distinct monoclonal T
      cell population in the bladder and gastric biopsies. The same analysis in the
      lymphocytic gastritis-like biopsy sample showed a monoclonal population with
      identical base pair size to that identified in the other specimens. This report
      highlights the importance of TCR gene rearrangement analysis in the diagnosis of
      unusual gastric inflammation, and the use of capillary electrophoresis based
      polymerase chain reaction in the follow up of lymphoproliferative disorders.

PMID- 15509691
TI  - Erdheim-Chester disease: case report with multisystemic manifestations including
      testes, thyroid, and lymph nodes, and a review of literature.
AB  - Erdheim-Chester disease is a rare non-Langerhans' cell histiocytosis with
      characteristic radiological and histological features. This entity is defined by
      a mononuclear infiltrate consisting of lipid laden, foamy histiocytes that stain
      positively for CD68. About half of those affected have extraskeletal
      manifestations, including involvement of the hypothalamus-pituitary axis, lung,
      heart, retroperitoneum, skin, liver, kidneys, spleen, and orbit. This report
      describes the case of a 50 year old white man who presented with hypogonadism and
      diabetes insipidus. At necropsy, extensive organ involvement was found, including
      the testes, thyroid, and lymph nodes. This is the first report of thyroid and
      lymph node infiltration in this disease. Because of the endocrinological
      symptoms, neurosarcoidosis and hypophysitis are important diseases in the
      differential diagnosis. This report also includes a review of the literature
      concerning rare organ manifestations and patients presenting primarily with
      similar symptoms.

PMID- 15509692
TI  - Miniature tissue microarrays for HercepTest standardisation and analysis.
AB  - AIMS: To assess the practicality of using a miniature tissue microarray (TMA)
      with several examples of each HercepTest score from 0 to 3+ as a control for
      routine HercepTest immunohistochemistry. METHODS: A TMA was constructed from in
      house cases of breast cancer where HercepTest on the whole sections showed scores
      0, 1+, 2+, or 3+. The TMA, which measured 5 x 5 mm, was designed with four rows
      (each representing scores 0, 1+, 2+, and 3+), with five 0.6 mm cores from
      separate cases. In all, 20 individual cases were represented and the TMA took
      less than one hour to construct. Fifty sequential 4 microm sections were cut from
      the TMA to maximise the number of available sections. They were stored at 4
      degrees C for 1-270 days and when a case needed HercepTest staining the section
      was added to the TMA tissue control slide. RESULTS: All slides contained tissue
      spots and immunohistochemical staining was consistent throughout the time period.
      CONCLUSIONS: The miniature TMA with examples of all HercepTest scores described
      here is an ideal tissue control and can be used as a visual reference for scoring
      a case. Slides stored at 4 degrees C could be used for up to 270 days.

PMID- 15509693
TI  - Targeting the use of ovarian cyst aspirate cytology.

PMID- 15509694
TI  - Plant gametogenesis: conservation and contrasts in development.
AB  - Although the process of gamete formation in plants has many unique features, much
      has been learnt from the comparative analysis between plants and other eukaryotic
      systems. Plants have a number of factors that have made them desirable for the
      analysis of gamete development; these include late germline specification, the
      non-lethality of mutations affecting gamete development and the large size of
      their chromosomes. The availability of the fully annotated Arabidopsis genome and
      comparative analysis using yeast, animal and E. coli has led to the
      identification and functional characterisation of many genes with roles in gamete
      development, principally those associated with meiosis, recombination and DNA
      repair. The advantages that plants give with the use of mutant screens to
      identify genes associated with gamete formation have also provided access to
      genes that are difficult to characterise by alternative routes. This has yielded
      novel information regarding the processes of gamete formation in higher plants.
      The times may now be changing with the advantages that plants provide serving to
      advance knowledge of gamete formation in other eukaryotic systems.

PMID- 15509695
TI  - Endogenous regulators of protein phosphatase-1 during mouse oocyte development
      and meiosis.
AB  - Reversible phosphorylation, involving protein kinases and phosphatases (PP), is
      important in regulating oocyte meiosis. Okadaic acid (OA) inhibition of PP1
      and/or PP2A stimulates oocyte germinal vesicle breakdown (GVB). In oocytes, PP1
      is localized in the cytoplasm and nucleus, yet endogenous regulation of oocyte
      PP1 has not been investigated. The objectives of the study were to identify intra
      oocyte mechanisms regulating PP1 during acquisition of OA-sensitive meiotic
      competence and meiotic resumption. Immunohistochemical studies revealed that GVB
      incompetent oocytes contained equivalent cytoplasmic and nuclear PP1. Upon
      development of OA-sensitive meiotic competence, PP1 displayed differential
      intracellular localization with significantly greater nuclear staining with
      distinct nucleolar rimming compared with cytoplasmic staining. Germinal vesicle
      intact oocytes contained neither nuclear inhibitor of PP1, nor PP1 cytoplasmic
      inhibitor-1 transcripts or proteins. Reverse transcription-PCR with PP1
      cytoplasmic inhibitor-2 (I2) primers and oocyte RNA amplified a predicted 330-bp
      product with the identical sequence to mouse liver I2. Oocytes contained a heat
      stable PP1 inhibitor with biochemical properties of I2. Phosphorylation of PP1 at
      Thr320 by cyclin dependent kinase-1 (CDK1) causes PP1 inactivation. Germinal
      vesicle-intact oocytes did not contain phospho-Thr320-PP1. Upon GVB, PP1 became
      phosphorylated at Thr320 and this phosphorylation did not occur if GVB was
      blocked with the CDK1 inhibitor, roscovitine (ROSC). Inhibition of oocyte GVB
      with ROSC was reversible and coincided with PP1 phosphorylation at Thr320.
      Increased oocyte staining of nuclear PP1 compared with cytoplasmic staining at a
      chronological stage when oocytes gain meiotic competence, and phosphorylation and
      inhibition of PP1 by CDK1 at or around GVB appear to be important mechanisms in
      regulating oocyte PP1 activity and meiosis. In addition, these studies provide
      further support for PP1 being the OA-sensitive PP important in the regulation of
      the acquisition of meiotic competence, nuclear events during meiotic arrest, and
      GVB.

PMID- 15509696
TI  - Two insulin-responsive glucose transporter isoforms and the insulin receptor are
      developmentally expressed in rabbit preimplantation embryos.
AB  - Glucose is the most important energy substrate for mammalian blastocysts. Its
      uptake is mediated by glucose transporters (GLUT). In muscle and adipocyte cells
      insulin stimulates glucose uptake by activation of the insulin receptor (IR)
      pathway and translocation of GLUT4. GLUT4 is expressed in bovine preimplantation
      embryos. A new insulin-responsive isoform, GLUT8, was recently described in mouse
      blastocysts. Thus, potentially, two insulin-responsive isoforms are expressed in
      early embryos. The mechanism of insulin action on embryonic cells, however, is
      still not clear. In the present study expression of IR, GLUT1, 2, 3, 4, 5 and 8
      was studied in rabbit preimplantation embryos using RT-PCR, Western blotting and
      immunohistochemistry. The rabbit mRNA sequences for the complete coding region of
      IR, GLUT4 and a partial GLUT8 sequence were determined by RACE-PCR and
      sequencing. GLUT4 was expressed in 3-day-old morulae and in 4- and 6-day-old
      blastocysts. IR and GLUT8 transcripts were detectable only in blastocysts.
      Blastocysts also expressed GLUT1 and 3, but not GLUT2 and 5. Transcript numbers
      of GLUT4 and 8 were higher in trophoblast than in embryoblast cells. Translation
      of IR, GLUT4 and 8 proteins in blastocysts was confirmed by Western blotting.
      GLUT4 was localized mainly in the membrane and in the perinuclear region in
      trophoblast cells while in embryoblast cells its localization was predominantly
      in the perinuclear cytoplasm. The possible function(s) of two insulin-responsive
      isoforms, GLUT4 and GLUT8, in rabbit preimplantation embryos needs further
      investigation. It may not necessarily be linked to insulin-stimulated glucose
      transport.

PMID- 15509697
TI  - Insulin acts via mitogen-activated protein kinase phosphorylation in rabbit
      blastocysts.
AB  - The addition of insulin during in vitro culture has beneficial effects on rabbit
      preimplantation embryos leading to increased cell proliferation and reduced
      apoptosis. We have previously described the expression of the insulin receptor
      (IR) and the insulin-responsive glucose transporters (GLUT) 4 and 8 in rabbit
      preimplantation embryos. However, the effects of insulin on IR signaling and
      glucose metabolism have not been investigated in rabbit embryos. In the present
      study, the effects of 170 nM insulin on IR, GLUT4 and GLUT8 mRNA levels, Akt and
      Erk phosphorylation, GLUT4 translocation and methyl glucose transport were
      studied in cultured day 3 to day 6 rabbit embryos. Insulin stimulated
      phosphorylation of the mitogen-activated protein kinase (MAPK) Erk1/2 and levels
      of IR and GLUT4 mRNA, but not phosphorylation of the phosphatidylinositol 3
      kinase-dependent protein kinase, Akt, GLUT8 mRNA levels, glucose uptake or GLUT4
      translocation. Activation of the MAPK signaling pathway in the absence of GLUT4
      translocation and of a glucose transport response suggest that in the rabbit
      preimplantation embryo insulin is acting as a growth factor rather than a
      component of glucose homeostatic control.

PMID- 15509698
TI  - The direct measurement of embryogenic volume and nucleo-cytoplasmic ratio during
      mouse pre-implantation development.
AB  - After fertilization, the mammalian conceptus undergoes cleavage, a process of
      cell proliferation in the absence of interphase growth. It is not known when
      cleavage ends and gives way to fully replicative cell cycles with a stable nucleo
      cytoplasmic ratio. We have used two-photon excitation and confocal microscopy to
      measure directly volumes and nucleo-cytoplasmic ratios of whole murine concepti
      and their individual constituent blastomeres during pre-implantation development
      up to the early uterine attachment stage (day 5). We show that the total
      cytoplasmic volume of the conceptus remains constant during pre-implantation
      development, and that the average nucleo-cytoplasmic ratio increases
      exponentially throughout the same period. Data from individual blastomeres show
      that both volume and nucleo-cytoplasmic ratio diverge in the inner and outer
      subpopulations evident from the 16-cell stage (fifth developmental cycle)
      onwards. Cells from emergent outer trophoblast populations are larger and have
      smaller nucleo-cytoplasmic ratios than those from emergent inner pluriblast
      populations. Moreover, the nucleo-cytoplasmic ratio of the trophoblast appears to
      be stabilizing, suggesting that for this subpopulation cleavage may end at the 16
      32-cell transition. Putative hypoblast and epiblast cell subpopulations within
      the pluriblast were not distinguishable by volume or nucleo-cytoplasmic ratio.
      Embryonic stem cell volume was higher than that of either cell subpopulation of
      expanded blastocysts, and their nucleo-cytoplasmic ratio was similar to that of
      trophoblast cells.

PMID- 15509699
TI  - Molecular cloning of porcine growth differentiation factor 9 (GDF-9) cDNA and its
      role in early folliculogenesis: direct ovarian injection of GDF-9 gene fragments
      promotes early folliculogenesis.
AB  - Growth differentiation factor-9 (GDF-9) is a growth factor secreted by oocytes in
      growing ovarian follicles. To investigate the ovarian function of GDF-9 in pigs,
      we first cloned porcine GDF-9 complementary DNA (cDNA), and then injected its
      gene fragments into the ovary in gilts. Porcine GDF-9 has open reading frame
      (ORF) homologies of 81.4%, 84.6%, 84.2%, 72.7% and 72.6% with its human, bovine,
      ovine, rat and mouse counterparts respectively. Regarding the deduced amino-acid
      sequence of the mature protein, the corresponding homologies reach 92.1%, 97.8%,
      97.0%, 89.6% and 88.1% respectively. To investigate the role of GDF-9 in early
      folliculogenesis, the ovaries of 2-month-old prepubertal gilts were injected with
      GDF-9 gene fragments. The injection of porcine GDF-9 gene fragments resulted in
      an increase in the number of primary, secondary and tertiary follicles,
      concomitant with a decrease in the number of primordial follicles. These results
      indicated that exogenous GDF-9 can promote early folliculogenesis in the porcine
      ovary, and that a technique for direct ovarian injection of GFD-9 gene fragments
      may contribute to a novel therapy for prevention and treatment of infertility
      associated with ovarian dysfunction.

PMID- 15509700
TI  - Cellular localization and changes in expression of prolactin receptor isoforms in
      sheep ovary throughout the estrous cycle.
AB  - The actions of prolactin (PRL) on target cells depend on the type of prolactin
      receptor (PRLr) predominantly expressed, particularly whether the long PRLr
      isoform is expressed. The aims of this study were to determine the cellular
      localization and the changes in expression of long and short PRLr isoforms in
      sheep ovary throughout the estrous cycle. Long and short PRLrs were localized
      mostly in the same ovarian cells. Maximum signal intensity, particularly for long
      PRLrs, was found in stromal cells surrounding primordial and primary follicles,
      and, for both PRLrs, in granulosa cells of preantral follicles and in luteal
      cells. Moderate signal intensity for PRLrs was found in theca cells of preantral
      to ovulatory follicles, and in granulosa cells of antral follicles up to the
      gonadotropin-dependent stage. Decreasing immunoreactivity to PRLrs was found in
      granulosa cells of gonadotropin-dependent to ovulatory follicles. For long PRLrs
      in particular, no signal was found in mural granulosa cells of gonadotropin
      dependent follicles; for both isoforms, no signal was found in most granulosa
      cells of ovulatory follicles. In primordial to gonadotropin-dependent follicles,
      cellular localization of PRLr was similar on days 0, 10 and 15 of the cycle.
      Oocytes consistently showed positive immunostaining for PRLrs. Comparative RT-PCR
      analysis of long and short PRLr expression showed that the short isoform is
      evenly expressed throughout the estrous cycle, whereas the expression of the long
      form increases at the time of estrus and decreases at mid-luteal phase and at the
      onset of the follicular phase. Expression of long PRLrs was greater than that of
      short PRLrs on day 0 of cycle; expression of both isoforms was similar on day 10
      and on day 15, long PRLrs expression was lower than that of short PRLrs. Our
      results indicate that in sheep ovary, the maximum responsiveness to PRL might
      occur during the preovulatory phase of the estrous cycle.

PMID- 15509701
TI  - Localization and temporal regulation of tissue inhibitors of metalloproteinases 3
      and 4 in bovine preovulatory follicles.
AB  - The matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are
      potential regulators of the focalized extracellular matrix degradation required
      for ovulation. The objectives of the present study were to determine localization
      and temporal regulation of TIMP-3 and TIMP-4 mRNA and protein in bovine
      preovulatory follicles. Ovaries containing preovulatory follicles were collected
      at 0, 12 and 20 h after GnRH injection for real-time PCR quantification of TIMP-3
      and TIMP-4 mRNAs and immunohistochemical localization studies. Additional samples
      collected at 0, 6, 12, 18 and 24 h post GnRH injection were subjected to Western
      analysis to determine temporal changes in TIMP-3 and TIMP-4 proteins in the apex
      and base of preovulatory follicles. Results indicate the gonadotropin surge
      regulates TIMP-3 and TIMP-4 expression. TIMP-3 and TIMP-4 mRNAs increased within
      12 h after GnRH injection. TIMP-3 protein was localized to granulosal and thecal
      layers of preovulatory follicles and adjacent ovarian stroma, whereas TIMP-4
      immunoreactivity was localized to granulosal and thecal cells and ovarian blood
      vessels. Amounts of TIMP-3 and TIMP-4 proteins in the follicular apex peaked
      within 12 h post GnRH injection and subsequently declined by 24 h. However,
      amounts of TIMP-3 and TIMP-4 proteins in the base were not elevated after GnRH
      administration. Results demonstrate that mRNA and protein for both TIMP-3 and
      TIMP-4 are increased in bovine preovulatory follicles following the gonadotropin
      surge. Coordinate expression of TIMPs and MMPs may help regulate the
      extracellular matrix remodeling characteristic of the ovulatory process.

PMID- 15509702
TI  - Genetic influences on ovulation of primary oocytes in LT/Sv strain mice.
AB  - A high proportion of LT/Sv strain oocytes arrest in meiotic metaphase I (MI) and
      are ovulated as diploid primary oocytes rather than haploid secondary oocytes.
      (Mus musculus castaneus x LT/SvKau)F1 x LT/SvKau backcross females were analysed
      for the proportion of oocytes that arrested in MI and typed by PCR for a panel of
      microsatellite DNA sequences (simple sequence repeat polymorphisms) that differed
      between strain LT/SvKau and M. m. castaneus. This provided a whole genome scan of
      86 genetic markers distributed over all 19 autosomes and the X chromosome, and
      revealed genetic linkage of the MI arrest phenotype to markers on chromosomes 1
      and 9. Identification of these two chromosomal regions should facilitate the
      identification of genes involved in mammalian oocyte maturation and the control
      of meiosis.

PMID- 15509703
TI  - Impaired fertility in T-stock female mice after superovulation.
AB  - Superovulation of female mice with exogenous gonadotrophins is routinely used for
      increasing the number of eggs ovulated by each female in reproductive and
      developmental studies. We report an unusual effect of superovulation on
      fertilization in mice. In vivo matings of superovulated T-stock females with
      B6C3F1 males resulted in a two-fold reduction (P <0.001) in the frequencies of
      fertilized eggs compared with control B6C3F1 matings. In addition, approximately
      22 h after mating, only 15% of fertilized eggs recovered in T-stock females had
      reached the metaphase stage of the first cleavage division versus 87% in B6C3F1
      females (P <0.0001). Matings with T-stock males did not improve the reproductive
      performance of T-stock females. To investigate the possible cause(s) for the
      impaired fertilization and zygotic development, the experiments were repeated
      using in vitro fertilization. Under these conditions, the frequencies of
      fertilized eggs were not different in superovulated T-stock and B6C3F1 females
      (51.7 +/- 6.0 and 64.5 +/- 3.8%, P=0.10). There was a seven-fold increase in the
      frequencies of fertilized eggs that completed the first cell cycle of development
      after in vitro versus in vivo fertilization in T-stock females. These results
      rule out an intrinsic deficiency of the T-stock oocyte as the main reason for the
      impaired fertility after in vivo matings, and suggest that superovulation of T
      stock females may induce a hostile oviductal and uterine environment with
      dramatic effects on fertilization and zygotic development.

PMID- 15509704
TI  - A close correlation in the expression patterns of Af-6 and Usp9x in Sertoli and
      granulosa cells of mouse testis and ovary.
AB  - Usp9x, an X-linked deubiquitylating enzyme, is stage dependently expressed in the
      supporting cells (i.e. Sertoli cells and granulosa cells) and germ cells during
      mouse gametogenesis. Af-6, a cell junction protein, has been identified as a
      substrate of Usp9x, suggesting a possible association between Usp9x and Af-6 in
      spermatogenesis and oogenesis. In this study, we examined the expression pattern
      of Af-6 and Usp9x and their intracellular localization in testes and ovaries of
      mice treated with or without pregnant mare serum gonadotropin (PMSG), an FSH-like
      hormone. In both testes and ovaries, Af-6 expression was predominantly observed
      in supporting cells, as well as in steroidogenic cells, but not in any germ
      cells. In Sertoli cells, Af-6 was continuously expressed throughout postnatal and
      adult stages, where both Af-6 and Usp9x were enriched at the sites of Sertoli
      Sertoli and Sertoli-spermatid junctions especially at stages XI-VI. In the
      granulosa cells, Af-6, as well as Usp9x, was highly expressed in primordial and
      primary follicles, but its expression rapidly decreased after the late-secondary
      follicle stage. Interestingly, in PMSG-treated mice, the expression levels of Af
      6 and Usp9x were synchronously enhanced, slightly in Sertoli cells and strongly
      in granulosa cells of the late-secondary and Graafian follicles. Such closely
      correlated expression patterns between Af-6 and Usp9x clearly suggest that Af-6
      may be deubiquitylated by Usp9x in both Sertoli and granulosa cells. It further
      suggests that the post-translational regulation of Af-6 by Usp9x may be one
      potential pathway to control the cell adhesion dynamics in mammalian
      gametogenesis.

PMID- 15509705
TI  - Intra-cytoplasmic sperm injection in a marsupial.
AB  - Here we report the first use of intra-cytoplasmic sperm injection (ICSI) in a
      marsupial, the tammar wallaby (Macropus eugenii), to achieve in vitro
      fertilization and cleavage. A single epididymal spermatozoon was injected into
      the cytoplasm of each mature oocyte collected from Graafian follicles or from the
      oviduct within hours of ovulation. The day after sperm injection, oocytes were
      assessed for the presence of pronuclei and polar body extrusion and in vitro
      development was monitored for up to 4 days. After ICSI, three of four (75%)
      follicular and four of eight (50%) tubal oocytes underwent cleavage. The cleavage
      pattern was similar to that previously reported for in vivo fertilized oocytes
      placed in culture, where development also halted at the 4- to 8-cell stage. One
      third of injected oocytes completed the second cleavage division, but only a
      single embryo reached the 8-cell stage. The success of ICSI in the tammar wallaby
      provided an opportunity to examine the influence of the mucoid coat that is
      deposited around oocytes passing through the oviduct after fertilization. The
      presence of a mucoid coat in tubal oocytes did not prevent fertilization by ICSI
      and the oocytes cleaved in vitro to a similar stage as follicular oocytes lacking
      a mucoid coat. Cell-zona and cell-cell adhesion occurred in embryos from
      follicular oocytes, suggesting that the mucoid coat is not essential for these
      processes. However, blastomeres were more closely apposed in embryos from tubal
      oocytes and cell-cell adhesion was more pronounced, indicating that the mucoid
      coat may be involved in maintaining the integrity of the conceptus during
      cleavage.

PMID- 15509706
TI  - Anti-inflammatory and proliferative responses in human and ovine ovarian surface
      epithelial cells.
AB  - The majority of ovarian cancers (>90%) are believed to derive from the ovarian
      surface epithelium (OSE); a single layer covering the entire surface of the
      ovary. At ovulation, the OSE cell layer undergoes an inflammatory response,
      involving cell death and growth, in order to overcome ovarian surface rupture.
      Abnormalities during these processes are believed to contribute to the
      development of tumours. Using primary cultures of OSE cells, we have compared
      anti-inflammatory and proliferative responses directly between human and ovine
      OSE cells to further establish the use of ovine OSE cells as a suitable model
      system for the study of human OSE cells. In order to compare effects of
      inflammatory stimulation, expression and activity of 11betahydroxysteroid
      dehydrogenase (11betaHSD) type 1 was measured in OSE cells in response to
      interleukin (IL)-1alpha. As previously identified in human OSE cells, treatment
      of ovine OSE cells with IL-1alpha stimulated a concomitant increase of 11betaHSD
      type 1 mRNA (31-fold; P <0.05) and oxoreductase activity, indicating an increased
      production of anti-inflammatory cortisol. To compare the growth of human and
      ovine OSE cells, OSE cell number was measured in response to treatment with
      gonadotropins or growth factors. In the presence of FSH, LH or human chorionic
      gonadotropin (hCG), ovine and human OSE cell growth was similarly stimulated >1.2
      fold (P <0.05). In the presence of connective tissue growth factor (CTGF) and
      more significantly insulin growth factor I (IGF-I), human and ovine OSE cell
      growth was also similarly stimulated >1.2-fold (P <0.05) and >1.5-fold (P <0.01),
      respectively. The induction of both human and ovine OSE cell growth by IGF-I or
      hCG was further shown to be dependent on activation of the MAP
      kinase/extracellular-signal-regulated kinase (ERK) pathway. Stimulation of ovine
      OSE cell growth by hepatocyte growth factor (HGF) was similarly shown to be ERK
      dependent; however, for human OSE cells, HGF only mildly stimulated ERK
      phosphorylation and failed to stimulate OSE cell growth. The demonstration that
      human and ovine OSE cells share similarities at the level of cell signalling,
      gene expression and cellular growth supports the use of ovine OSE cells as a
      suitable model for the study of human OSE cells.

PMID- 15509707
TI  - Hoechst 33342 stain and u.v. laser exposure do not induce genotoxic effects in
      flow-sorted boar spermatozoa.
AB  - Sex selection by flow cytometry/cell sorting involves the staining of spermatozoa
      with Hoechst 33342 in combination with the impact of a u.v. laser beam, two
      potentially mutagenic agents. A phenotypic and cytogenetic study of lymphocytes
      of piglets born after insemination with spermatozoa stained with Hoechst 33342
      and from piglets obtained from stain-sorted spermatozoa was performed to evaluate
      the genotoxic effect of Hoechst 33342 staining and u.v. laser irradiation on the
      offspring. Lymphocytes from piglets born after insemination with unstained
      spermatozoa, but from the same ejaculate, were used as a control group.
      Peripheral blood lymphocytes from these piglets were cultured following a
      standard cell culture protocol. Cells were then collected by centrifugation,
      subjected to hypotonic solution and fixed and dropped onto slides. Sister
      chromatid exchanges (SCEs) and chromosome aberrations (CAs: including chromosome
      and chromatid breaks) per cell were scored in 50-s division metaphase spreads
      from each donor. Reproductive parameters and litter performance of all
      inseminations performed were also recorded in all groups. Data were analyzed by
      ANOVA. No significant increase (P > 0.05) of SCE and CA frequencies were observed
      in piglets born from stained spermatozoa or from stain-sorted spermatozoa with
      respect to controls (untreated sperm). The results indicated that no mutagenic
      effect on spermatozoa, expressed as increases in the incidence of abnormalities
      in the resulting offspring and also as increases in SCE and CA frequencies on
      lymphocytes from these individuals, was induced by the staining of boar
      spermatozoa with Hoechst 33342, nor by combination of staining with laser impact
      during flow cytometry.

PMID- 15509708
TI  - Use of parentage testing to determine optimum insemination time and culture media
      for oocyte transfer in mares.
AB  - Parentage identification was used to test the developmental competence of oocytes
      cultured under different conditions and fertilized in vivo after oocyte transfer.
      Oocytes were collected transvaginally from follicles of estrous mares
      approximately 22 h after administration of human chorionic gonadotropin. Oocytes
      were cultured for approximately 16 h in one of three media, with or without
      addition of hormones and growth factors. Groups of three or four oocytes,
      cultured in different media, were transferred into the oviduct contralateral to a
      recipient's own ovulation. Recipients were inseminated with semen from two
      different stallions at 15 h before and 2.5 h after oocyte transfer. Sixteen days
      after transfer, embryos were recovered from uteri and submitted for parentage
      testing. The percentage of oocytes resulting in embryonic vesicles was nearly
      identical (P >0.05) for transferred oocytes (32/44, 73%) versus ovulated oocytes
      of recipients (9/13, 69%). More (P <0.01) oocytes were fertilized by sperm
      inseminated before (35/38, 92%) versus after (3/38, 8%) oocyte transfer. Tissue
      culture medium (TCM)-199 was superior to equine maturation medium I (EMMI; a SOF
      based medium) for culturing oocytes (P <0.05), although addition of hormones and
      growth factors during culture did not improve (P >0.05) development of embryos.

PMID- 15509709
TI  - Semen-induced luteal phase and identification of a LH surge in the koala
      (Phascolarctos cinereus).
AB  - The koala ovulates in response to mating. The purpose of this study was to
      document the LH surge induced by copulation and to investigate the potential
      roles of mechanical stimulation of the urogenital sinus and deposition of semen
      in induction of the luteal phase. In experiment 1, serial blood samples from four
      koalas that underwent normal mating showed elevated concentrations of LH
      approximately 24-32 h post-coitus. There was no corresponding elevation in LH in
      koalas (n=4) that were exposed to the presence of a male but received no physical
      contact. In experiment 2, koalas on day 2 of oestrus were exposed to one of the
      following treatments (n=9 per group): artificial insemination with 1 ml 0.9%
      sterile saline (control group), insemination with 1 ml koala semen, stimulation
      of the urogenital sinus with a purpose built glass rod (designed to mimic the
      action of the penis during natural mating) and urogenital stimulation with the
      glass rod followed by insemination of 1 ml koala semen. Confirmation of a luteal
      phase was based on evidence of a prolonged return to oestrus, parturition and/or
      elevated progesterone concentrations. Insemination of saline (0/9) and urogenital
      stimulation (0/9) failed to induce a luteal phase. Insemination of semen without
      glass rod stimulation resulted in a luteal phase in 4/9 koalas, three of which
      gave birth. Insemination of semen in combination with urogenital stimulation
      produced a luteal phase in 7/9 koalas, four of which gave birth. Semen had a
      significant effect on induction of the koala luteal phase (P <0.001) but glass
      rod stimulation had no such effect (P=0.335). It was concluded that semen must be
      involved in the induction of a luteal phase in the koala. The results presented
      in this study will serve to improve optimal timing and induction of ovulation for
      artificial insemination in the koala.

PMID- 15509710
TI  - Selenium deficiency as a model of experimental pre-eclampsia in rats.
AB  - Epidemiological studies and in vitro analysis demonstrate correlations between
      selenium status and human pre-eclampsia (PET). Selenium is an essential component
      in the anti-oxidant proteins glutathione peroxidase and thioredoxin reductase,
      which are produced in lower amounts in pre-eclamptic placenta. This study
      examined the effect of modulating dietary selenium content in pregnant rats. Rats
      were fed diets containing no selenium, 239 microg/kg selenium or 1000 microg/kg
      selenium, four weeks prior to and following conception. Significant pregnancy
      specific increases in systolic blood pressure (116.4 +/- 5.2 mmHg vs 108 +/- 6.8
      mmHg vs 111.4 +/- 4.7 mmHg) and proteinuria (9.68 +/- 2.12 microg/ml vs 5.93 +/-
      1.59 microg/ml vs 4.43 +/- 0.96 microg/ml) were demonstrated in animals fed a
      selenium free-diet when compared with normal or high selenium diets. Placental
      weight and pup number were not affected by selenium deprivation, however a
      significant decrease in the pup weight was evident. Selenium deprivation caused
      dose-dependent decreases in liver glutathione peroxidase (28.55 +/- 3.82
      mmoles/min/mg vs 34.68 +/- 8.64 mmoles/min/mg) and thioredoxin reductase (2.37 +/
      1.25 U/mg vs 6.68 +/- 1.82 U/mg) activity, whereas superoxide dismutase activity
      remained constant. Placental activity of these enzymes also decreased leading to
      oxidative stress as measured by increased lipid peroxides (17.92 +/- 1.78
      micromoles/mg vs 8.30 +/- 5.52 micromoles/mg) and protein carbonyls in tissue
      extracts from selenium-free animals. These results suggest that selenium
      deficiency in pregnant rats leads to symptoms similar to those seen in human PET
      and may provide an experimental model for studying this complex disease.

PMID- 15509711
TI  - Serine-threonine kinases and transcription factors active in signal transduction
      are detected at high levels of phosphorylation during mitosis in preimplantation
      embryos and trophoblast stem cells.
AB  - Serine-threonine kinases and transcription factors play important roles in the G1
      S phase progression of the cell cycle. Assays that use quantitative fluorescence
      by immunocytochemical means, or that measure band strength during Western blot
      analysis, may have confused interpretations if the intention is to measure G1-S
      phase commitment of a small subpopulation of phosphorylated proteins, when a
      larger conversion of the same population of proteins can occur during late G2 and
      M phases. In mouse trophoblast stem cells (TSC), a human placental cell line
      (HTR), and/or mouse preimplantation embryos, 8/19 serine-threonine and tyrosine
      kinases, 3/8 transcription factors, and 8/14 phospho substrate and miscellaneous
      proteins were phosphorylated at higher levels in M phase than in interphase. Most
      phosphoproteins appeared to associate with the spindle complex during M phase,
      but one (p38MAPK) associated with the spindle pole and five (Cdx2, MEK1, 2, p27,
      and RSK1) associated with the DNA. Phosphorylation was detected throughout
      apparent metaphase, anaphase and telophase for some proteins, or for only one of
      these segments for others. The phosphorylation was from 2.1- to 6.2-fold higher
      during M phase compared with interphase. These data suggest that, when planning
      and interpreting quantitative data and perturbation experiments, consideration
      must be given to the role of serine-threonine kinases and transcription factors
      during decision making in M phase as well as in G1-S phase.

PMID- 15509712
TI  - P-glycoprotein substrate binding domains are located at the transmembrane
      domain/transmembrane domain interfaces: a combined photoaffinity labeling-protein
      homology modeling approach.
AB  - P-glycoprotein (P-gp) is an energy-dependent multidrug efflux pump conferring
      resistance to cancer chemotherapy. Characterization of the mechanism of drug
      transport at a molecular level represents an important prerequisite for the
      design of pump inhibitors, which resensitize cancer cells to standard
      chemotherapy. In addition, P-glycoprotein plays an important role for early
      absorption, distribution, metabolism, excretion, and toxicity profiling in drug
      development. A set of propafenonetype substrate photoaffinity ligands has been
      used in this study in conjunction with matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry to define the substrate
      binding domain(s) of P-gp in more detail. The highest labeling was observed in
      transmembrane segments 3, 5, 8, and 11. A homology model for P-gp was generated
      on the basis of the dimeric crystal structure of Vibrio cholerae MsbA, an
      essential lipid transporter. Thereafter, the labeling pattern was projected onto
      the 3D atomic-detail model of P-gp to allow a visualization of the binding
      domain(s). Labeling is predicted by the model to occur at the two transmembrane
      domain/transmembrane domain interfaces formed between the amino- and carboxyl
      terminal half of P-gp. These interfaces are formed by transmembrane (TM) segments
      3 and 11 on one hand and TM segments 5 and 8 on the other hand. Available data on
      LmrA and AcrB, two bacterial multidrug efflux pumps, suggest that binding at
      domain interfaces may be a general feature of polyspecific drug efflux pumps.

PMID- 15509713
TI  - Cyclooxygenase inhibitors induce the expression of the tumor suppressor gene EGR
      1, which results in the up-regulation of NAG-1, an antitumorigenic protein.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to have
      chemopreventive activity, but the mechanisms involved are not clearly understood.
      Although NSAIDs inhibit cyclooxygenase activity, they also increase the
      expression of a divergent member of the transforming growth factor-beta
      superfamily, termed NSAID-activated gene 1 (NAG-1), a protein with an
      antitumorigenic and proapoptotic activity that could in part be linked to the
      chemoprevention activity of NSAIDs. NAG-1 is induced by some NSAIDs, but the
      mechanisms responsible are not clear. In this report, we have identified a cis
      acting element responsive to NSAIDs located within the -73 to -51 region of the
      NAG-1 promoter. This region contains overlapping EGR-1 and Sp1 binding sites, and
      mutations in this region suggest that the transcription factors have an important
      role in NSAID-induced NAG-1 expression. EGR-1 was found to play a critical role
      in the induction of NAG-1 by sulindac sulfide and other NSAIDs. NSAIDs increase
      EGR-1 protein expression that occurs before the induction of NAG-1 expression,
      supporting the hypothesis that EGR-1 is necessary for NSAID-induced NAG-1
      expression. Thus, NSAIDs induce the expression of EGR-1, a tumor suppressor gene,
      providing a novel mechanism to explain, in part, the antitumorigenic properties
      of some NSAIDs. NAG-1 seems to be an important downstream target protein of this
      transcription factor, EGR-1, and may mediate the chemopreventive activity of some
      NSAIDs.

PMID- 15509714
TI  - Characterization of binding of folates and antifolates to brush-border membrane
      vesicles isolated from human kidney.
AB  - Antifolates such as methotrexate, raltitrexed, and pemetrexed are among the most
      effective and widely used anticancer drugs. The antifolates are also among the
      most unpredictable of anticancer drugs with respect to pharmacokinetics and
      toxicity. In this study, we assessed the binding of folates and antifolates to
      the folate receptors (FRs) of human proximal tubules and the effects of pH on
      binding. Binding of [(3)H]folic acid was pH-dependent, with maximal binding seen
      at pH 6. Equilibrium binding experiments with [(3)H]folic acid showed that K(d)
      values were unaffected, and B(max) values increased as the pH was decreased from
      8.0 to 6.0. Increasing the osmolarity at pH 6.0 had no effect on intravesicular
      content, confirming that increased site-specific binding caused the observed
      changes in B(max) values. Enzymatic cleavage of glycosyl-phosphatidylinositol
      linkages abolished binding of [(3)H]folic acid to brush-border membrane vesicles,
      suggesting that [(3)H]folic acid was bound to FRs. In concentration-effect
      experiments conducted at different pH values, the antifolates raltitrexed and
      (2S)-2-[o-fluoro-p-[N-(2,7-dimethyl-4-oxo-3,4-dihydroquinazolin-6-yl-methyl)-N
      (prop-2-ynyl)amino]benzamido]-4-(tetrazol-5-yl) butyric acid (ZD9331) bound more
      tightly as pH increased from 6.0 to 8.0, whereas binding of 10-propargyl-5,8
      dideazafolic acid (CB3717) was unchanged. The results obtained when K(i) values
      were converted to binding energies suggested that binding of some, but not all,
      antifolates and folates to FRs was pH-dependent, further indicating roles of
      luminal pH in renal reabsorption or secretion processes.

PMID- 15509715
TI  - Picrotoxin accelerates relaxation of GABAC receptors.
AB  - Picrotoxin is a plant alkaloid that is often used to block the activity of
      neuronal GABA and glycine receptors. However, the mechanism by which picrotoxin
      inhibits these receptors is still in debate. In this study, we investigated the
      picrotoxin inhibition on perch-rho subunits expressed heterologously in Xenopus
      laevis oocytes, and on native GABA(C) receptors of perch bipolar cells. Both
      competitive and noncompetitive mechanisms were observed for picrotoxin inhibition
      of the GABA(C) receptor. In oocytes expressing the rho1A subunit, terminating
      simultaneously the coapplication of GABA and picrotoxin induced a large rebound
      of membrane current. In addition, picrotoxin significantly accelerated the
      kinetics of GABA responses, particularly in the relaxation (offset) phase of GABA
      currents. Both current rebound and the large acceleration of GABA relaxation were
      unique to picrotoxin inhibition and were not observed with the competitive
      antagonist (1,2,5,6-tetrahydropyridin-4-yl)-methylphosphinic acid or the
      allosteric modulator zinc. The change in kinetics induced by picrotoxin was also
      observed on receptors formed by other GABA rho subunits, as well as on the
      GABA(C) receptors of retinal bipolar cells. Based on these observations, we
      proposed a model in which picrotoxin binds to the GABA(C) receptor in both
      channel open and closed states. Overall, this model provides a remarkably good
      approximation of the experimental findings we observed for picrotoxin inhibition
      of GABA(C) receptors. These results support an allosteric mechanism of picrotoxin
      inhibition of ligand-gated chloride channels.

PMID- 15509716
TI  - Evidence for negative binding cooperativity within CCR5-CCR2b heterodimers.
AB  - It is well established that most G protein-coupled receptors are able to form
      homo- and heterodimers, although the functional consequences of this process
      often remain unclear. CCR5 is a chemokine receptor that plays an important role
      in inflammatory diseases and acts as a major coreceptor for human
      immunodeficiency viruses. CCR5 was previously shown to homodimerize and
      heterodimerize with CCR2b, a closely related receptor. In the present study, we
      have analyzed the functional consequences of this dimerization process, in terms
      of ligand binding, stimulation of intracellular cascades, and internalization.
      Bioluminescence resonance energy transfer and coimmunoprecipitation assays
      demonstrated that CCR5 and CCR2b heterodimerize with the same efficiency as they
      homodimerize. In contrast to what has been reported previously, no cooperative
      signaling was observed after costimulation of the two receptors by their
      respective ligands. However, we observed that CCR5-specific ligands that are
      unable to compete for monocyte chemoattractant protein (MCP-1) binding on cells
      expressing CCR2b alone efficiently prevented MCP-1 binding when CCR5 and CCR2b
      were coexpressed. The extent of this cross-competition was correlated with the
      amount of CCR5 expressed in cells, as determined by fluorescence-activated cell
      sorting analysis. Similar observations were made for the CCR2b-selective ligand
      MCP-1 that competed efficiently for macrophage inflammatory protein-1beta binding
      on cells expressing both receptors. Internalization assays did not allow us to
      demonstrate cointernalization of the receptors in response to agonist
      stimulation. Together, our observations suggest that CCR5 and CCR2b form homo-
      and heterodimers with similar efficiencies and that a receptor dimer can only
      bind a single chemokine.

PMID- 15509717
TI  - Current techniques and results of liver resection for colorectal liver
      metastases.
AB  - Colorectal cancer remains the second most common cause of cancer death in the
      West. Every year in the UK alone, around 14 000 patients develop secondary
      hepatic deposits from a primary colorectal cancer. Surgery remains the mainstay
      of treatment for liver metastases. Although not every patient is a candidate for
      surgery, earlier referral and rapid assessment are required to improve outcome.
      With the use of most recent technologies and radical surgery, increasing numbers
      of patients should have therapy with curative intent. This paper reviews
      preoperative patient evaluation and selection, surgical strategies, adjuvant
      therapy and postoperative follow-up. Other treatment modalities to increase
      tumour resectability are also described.

PMID- 15509718
TI  - Current status of the debate on laparoscopic hernia repair.
AB  - There is continued debate as to the role of laparoscopy in recurrent, bilateral
      inguinal and incisional hernias. Further clinical trials are needed in all of
      these areas. For patients with a primary inguinal hernia laparoscopic repair can
      no longer be recommended as the repair of choice unless it is undertaken in an
      expert centre in minimal access surgery.

PMID- 15509719
TI  - [(pF)Phe4,Arg14,Lys15]N/OFQ-NH2 (UFP-102), a highly potent and selective agonist
      of the nociceptin/orphanin FQ receptor.
AB  - A novel ligand for the nociceptin/orphanin FQ (N/OFQ) receptor (NOP),
      [(pF)Phe(4),Arg(14),Lys(15)]N/OFQ-NH(2) (UFP-102), has been generated by
      combining in the N/OFQ-NH(2) sequence two chemical modifications,
      [Arg(14),Lys(15)] and [(pF)Phe(4)], that have been previously demonstrated to
      increase potency. In vitro, UFP-102 bound with high affinity to the human NOP
      receptor, showed at least 200-fold selectivity over classical opioid receptors,
      and mimicked N/OFQ effects in CHO(hNOP) cells, isolated tissues from various
      species, and mouse cortical synaptosomes releasing 5-hydroxytryptamine. UFP-102
      showed similar maximal effects but higher potency (2- to 48-fold) relative to
      N/OFQ. The effects of UFP-102 were sensitive to NOP-selective antagonists J
      113397 [(+/-)-trans-1-[1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl
      1,3-dihydro-2H-benzimidazol-2-one] (pA(2) = 7.75-8.12) and UFP-101
      ([Nphe(1),Arg(14),Lys(15)]N/OFQ-NH(2))(pA(2) = 6.91-7.33) but not to naloxone,
      and no longer observed in tissues taken from NOP receptor knockout mice (NOP(-/
      )). In vivo, UFP-102 (0.01-0.3 nmol i.c.v.) mimicked the pronociceptive action of
      N/OFQ (0.1-10 nmol i.c.v.) in the mouse tail withdrawal assay, displaying higher
      potency and longer lasting effects. The action of UFP-102 was not apparent in
      NOP(-/-) mice. Similar results were obtained measuring locomotor activity in
      mice. In conscious rats, UFP-102 (0.05 nmol i.c.v.) produced a marked and
      sustained decrease in heart rate, mean arterial pressure, and urinary sodium
      excretion and a profound increase in urine flow rate. These effects were
      comparable with those evoked by N/OFQ at 5 nmol. Collectively, these findings
      demonstrate that UFP-102 behaves as a highly potent and selective NOP receptor
      agonist that produces long-lasting effects in vivo.

PMID- 15509720
TI  - Amiloride peptide conjugates: prodrugs for sodium-proton exchange inhibition.
AB  - Inhibition of the sodium-proton exchanger (NHE) plays an important role in
      reducing tissue damage during ischemic reperfusion injury; however,
      pharmacological inhibitors of NHE have restricted access to acutely ischemic
      tissues because of severely compromised tissue perfusion. We describe the
      syntheses, characterization, and NHE inhibitory activities of a novel class of
      amiloride derivatives where peptides are conjugated to the amiloride C(5) amino
      group. These new peptide-C(5)-amiloride conjugates are inactive; however, peptide
      residues were chosen such that selective cleavage by neutral endopeptidase 24.11
      (enkephalinase) liberates an amino acid-C(5)-amiloride conjugate that inhibits
      NHE in a glial cell line. These results confirm the feasibility of using peptide
      amiloride conjugates as NHE inhibitor prodrugs. We envision the design of
      analogous peptide-amiloride prodrugs that can be administered prior to ischemic
      events and subsequently activated by endopeptidases selectively expressed by
      ischemic tissues.

PMID- 15509721
TI  - The effects of tamoxifen and its metabolites on platelet function and release of
      reactive oxygen intermediates.
AB  - Tamoxifen is effective in the prevention and treatment of breast cancer, but its
      use is associated with an increased risk of thrombosis. The mechanism for this
      effect is unknown. Reactive oxygen intermediates enhance platelet-dependent
      thrombosis, and in oncological studies, tamoxifen has been shown to increase
      production of reactive oxygen species. Therefore, the effects of tamoxifen and
      its bioactive metabolites on platelet activity and platelet reactive oxygen
      species were determined. Platelets were incubated with tamoxifen or the
      metabolites 4-hydroxy-tamoxifen (4-OH), N-desmethyl tamoxifen, or 4-hydroxy-N
      desmethyl tamoxifen (endoxifen). Tamoxifen metabolites have been previously shown
      to possess enhanced bioactivity, and consistent with this observation, tamoxifen
      metabolites but not tamoxifen modestly increased platelet aggregation. These
      effects were similar with platelets isolated from male or female subjects.
      Platelet nitric oxide release or cGMP levels were not altered by incubation with
      tamoxifen or any of its metabolites. Incubation with tamoxifen metabolites
      increased stimulation-dependent platelet superoxide release [8.1 +/- 1.6
      arbitrary units (a.u.) for control versus 15.2 +/- 3.5 a.u. for 4-OH; P < 0.01].
      Coincubation with a superoxide dismutase mimetic eliminated the tamoxifen
      metabolite-induced enhancement of platelet aggregation. Corresponding to
      increased superoxide release, incubation with tamoxifen metabolites enhanced the
      functional activation of NADPH oxidase as determined by phosphorylation of its
      subunits p47(phox) and p67(phox). In summary, incubation of platelets with the
      active metabolites of tamoxifen increases stimulation-dependent superoxide
      release through a NADPH oxidase-dependent mechanism. This results in modest
      changes in platelet function and seems to be consistent with previous oncological
      studies demonstrating tamoxifen-dependent increase in reactive oxygen species
      generation.

PMID- 15509722
TI  - Bioactivation of the pulmonary toxicants naphthalene and 1-nitronaphthalene by
      rat CYP2F4.
AB  - Naphthalene, a ubiquitous environmental contaminant, produces cytotoxicity in
      nonciliated bronchiolar epithelial (Clara) cells in mice; rats are refractory to
      lung cytotoxicity from naphthalene. In contrast, 1-nitronaphthalene is a potent
      toxicant in both species. Naphthalene is metabolized by CYP2F to a 1,2-epoxide,
      the first and obligate step in events leading to cytotoxicity. 1-Nitronaphthalene
      is metabolized to both the 5,6- and the 7,8-epoxides with the 7,8-epoxide
      predominating in lung. Previous studies have demonstrated recombinant CYP2F2
      (mouse) to efficiently metabolize both naphthalene and 1-nitronaphthalene. To
      better understand the mechanism for the unique toxicity profiles for both
      compounds, a CYP2F ortholog (CYP2F4) was isolated from rat lung and expressed
      using a baculovirus system. Recombinant CYP2F4 efficiently generates 1R,2S
      naphthalene oxide (K(m) = 3 microM, V(max) = 107 min(-1)) and the 5,6- and 7,8
      epoxides of 1-nitronaphthalene (K(m) = 18 microM, V(max) = 25 min(-1) based on
      total generated glutathione conjugates). Kinetics and regio/stereoselectivity of
      rat CYP2F4 were indistinguishable from mouse CYP2F2. These results, combined with
      our recent immunomapping studies demonstrating minimal pulmonary CYP2F expression
      in rats, indicate that CYP2F expression is the factor most clearly associated
      with susceptibility to naphthalene-induced pneumotoxicity. CYP2F4 failed to
      display an enhanced ability to bioactivate 1-nitronaphthalene, an ability that
      could have potentially compensated for the lower CYP2F pulmonary expression
      levels in the rat, yet equal species susceptibilities. These results suggest the
      importance of other P450 enzymes in the epoxidation/bioactivation of 1
      nitronaphthalene. Expression of recombinant CYP2F1 (human) yielded an
      immunoreactive protein with no detectable CO-difference spectrum suggesting
      inadequate heme incorporation.

PMID- 15509723
TI  - Nitrogen-fixing bacterium Burkholderia brasiliensis produces a novel yersiniose A
      containing O-polysaccharide.
AB  - Burkholderia brasiliensis, a Gram-negative diazotrophic endophytic bacterium, was
      first isolated from roots, stems, and leaves of rice plant in Brazil. The
      polysaccharide moiety was released by ammonolysis from the B. brasiliensis
      lipopolysaccharide (LPS), allowing the unambiguous characterization of a 3,6
      dideoxy-4-C-(1-hydroxyethyl)-D-xylo-hexose (yersiniose A), an uncommon feature
      for Burkholderia LPS. The complete structure of the yersiniose A-containing O
      antigen was identified by sugar and methylation analyses and NMR spectroscopy.
      Our results show that the repeating oligosaccharide motif of LPS O-chain consists
      of a branched tetrasaccharide with the following structure:-->2-alpha-d-Rhap-(1-
      >3)-[alpha-YerAp-(1-->2)]-alpha-D-Rhap-(1-->3)-alpha-D-Rhap-(1-->.

PMID- 15509724
TI  - A genetic algorithm approach to detecting lineage-specific variation in selection
      pressure.
AB  - The ratio of nonsynonymous (dN) to synonymous (dS) substitution rates, omega,
      provides a measure of selection at the protein level. Models have been developed
      that allow omega to vary among lineages. However, these models require the
      lineages in which differential selection has acted to be specified a priori. We
      propose a genetic algorithm approach to assign lineages in a phylogeny to a fixed
      number of different classes of omega, thus allowing variable selection pressure
      without a priori specification of particular lineages. This approach can identify
      models with a better fit than a single-ratio model, and with fits that are better
      than (in an information theoretic sense) a fully local model, in which all
      lineages are assumed to evolve under different values of omega, but with far
      fewer parameters. By averaging over models which explain the data reasonably
      well, we can assess the robustness of our conclusions to uncertainty in model
      estimation. Our approach can also be used to compare results from models in which
      branch classes are specified a priori with a wide range of credible models. We
      illustrate our methods on primate lysozyme sequences and compare them with
      previous methods applied to the same data sets.

PMID- 15509725
TI  - The cellular retinol-binding protein genes are duplicated and differentially
      transcribed in the developing and adult zebrafish (Danio rerio).
AB  - There are single copies of the genes encoding the cellular retinol-binding
      protein type I and II (CRBPI and CRBPII) in the human and rodent genomes. We have
      identified duplicate genes for both CRBPI and CRBPII in the zebrafish (Danio
      rerio) genome (rbp1b and rbp2b). The zebrafish rbp1b and rbp2b have conserved
      gene structures, amino acid sequence similarities, gene phylogenies, and syntenic
      relationships with their mammalian orthologs and zebrafish paralogs, rbp1a and
      rbp2a. Like the mammalian genes for CRBPI and CRBPII, the zebrafish rbp1b and
      rbp2b genes are closely linked on a single linkage group. Comparative analysis
      suggests that the duplicate genes of rbp1 and rbp2 in the zebrafish genome may
      have arisen by chromosomal or whole-genome duplication. During embryonic
      development, rbp1b transcripts were detected in the gall bladder of 5-day
      postfertilization (5 dpf) larvae. The rbp2b mRNA was abundant in the developing
      liver through 48 hours postfertilization (48 hpf) to 5 dpf. Using reverse
      transcription-polymerase chain reaction (RT-PCR), rbp1b transcripts were detected
      in the ovary, and rbp2b mRNA was observed predominantly in the adult liver.
      Tissue section in situ hybridization and emulsion autoradiography localized rbp1b
      mRNA to primary oocytes within the zebrafish ovary. The differential mRNA
      distribution patterns of the rbp1a, rbp1b, rbp2a, and rbp2b genes in the
      developing and adult zebrafish suggest that shuffling of subfunctions among
      duplicate copies of paralogous genes may be a mechanism for the retention of
      duplicated genes in vertebrates.

PMID- 15509726
TI  - A statistical characterization of consistent patterns of human immunodeficiency
      virus evolution within infected patients.
AB  - Within-patient HIV populations evolve rapidly because of a high mutation rate,
      short generation time, and strong positive selection pressures. Previous studies
      have identified "consistent patterns" of viral sequence evolution. Just before
      HIV infection progresses to AIDS, evolution seems to slow markedly, and the
      genetic diversity of the viral population drops. This evolutionary slowdown could
      be caused either by a reduction in the average viral replication rate or because
      selection pressures weaken with the collapse of the immune system. The former
      hypothesis (which we denote "cellular exhaustion") predicts a simultaneous
      reduction in both synonymous and nonsynonymous evolution, whereas the latter
      hypothesis (denoted "immune relaxation") predicts that only nonsynonymous
      evolution will slow. In this paper, we present a set of statistical procedures
      for distinguishing between these alternative hypotheses using DNA sequences
      sampled over the course of infection. The first component is a new method for
      estimating evolutionary rates that takes advantage of the temporal information in
      longitudinal DNA sequence samples. Second, we develop a set of probability models
      for the analysis of evolutionary rates in HIV populations in vivo. Application of
      these models to both synonymous and nonsynonymous evolution affords a comparison
      of the cellular-exhaustion and immune-relaxation hypotheses. We apply the
      procedures to longitudinal data sets in which sequences of the env gene were
      sampled over the entire course of infection. Our analyses (1) statistically
      confirm that an evolutionary slowdown occurs late in infection, (2) strongly
      support the immune-relaxation hypothesis, and (3) indicate that the cessation of
      nonsynonymous evolution is associated with disease progression.

PMID- 15509727
TI  - Physicochemical evolution and molecular adaptation of the cetacean and
      artiodactyl cytochrome b proteins.
AB  - Cetaceans have most likely experienced metabolic shifts since evolutionarily
      diverging from their terrestrial ancestors, shifts that may be reflected in the
      proteins such as cytochrome b that are responsible for metabolic efficiency.
      However, accepted statistical methods for detecting molecular adaptation are
      largely biased against even moderately conservative proteins because the primary
      criterion involves a comparison of nonsynonymous and synonymous substitution
      rates (dN/dS); they do not allow for the possibility that adaptation may come in
      the form of very few amino acid changes. We apply the MM01 model to the possible
      molecular adaptation of cytochrome b among cetaceans because it does not rely on
      a dN/dS ratio, instead evaluating positive selection in terms of the amino acid
      properties that comprise protein phenotypes that selection at the molecular level
      may act upon. We also apply the codon-degeneracy model (CDM), which focuses on
      evaluating overall patterns of nucleotide substitution in terms of base exchange,
      codon position, and synonymy to estimate the overall effect of selection. Using
      these relatively new models, we characterize the molecular adaptation that has
      occurred in the cetacean cytochrome b protein by comparing revealed amino acid
      replacement patterns to those found among artiodactyls, the modern terrestrial
      mammals found to be most closely related to cetaceans. Our findings suggest that
      several regions of the cetacean cytochrome b protein have experienced molecular
      adaptation. Also, these adaptations are spatially associated with domain
      structure, protein function, and the structure and function of the cytochrome
      bc(1) complex and its constituents. We also have found a general correlation
      between the results of the analytical software programs TreeSAAP (which
      implements the MM01 model) and CDM (which implements the codon-degeneracy model).

PMID- 15509728
TI  - Prenatal programming of reproductive neuroendocrine function: the effect of
      prenatal androgens on the development of estrogen positive feedback and ovarian
      cycles in the ewe.
AB  - Exposure of the female ovine fetus to male hormones during a sensitive window of
      in utero life causes disruption to reproductive function. In some animals,
      androgen exposure completely abolishes reproductive cycles, but in others, cycles
      are progressively lost with age. The present study tested two predictions: that
      noncycling, androgenized animals are unable to respond to estrogen with a
      preovulatory-like surge of LH (estrogen positive feedback), and that the
      androgenized animals that exhibit a progressive loss of cycles also show a
      progressive loss of estrogen positive feedback. Androgenized ewes were generated
      by injection of their mothers with testosterone propionate twice per week from
      Day 30 to Day 90 of pregnancy (term, 147 days). Control ewes received no
      injections. Whether ewes could exhibit estrogen positive feedback was tested on
      five occasions before puberty (30 wk) and once during the anestrous period. All
      control animals had repeated reproductive cycles in both the first and second
      breeding season, and all showed robust LH surges during test periods. Despite the
      fact that 64% of androgenized animals showed reproductive cycles, estrogen
      positive feedback could be demonstrated in only 6.1% of trials. Subsequent
      experiments revealed that the lack of response to estrogen in androgenized
      animals was not because of pituitary insensitivity to GnRH, a requirement for
      higher concentrations of estrogen, or a surge that was delayed relative to the
      time of estrogen administration. The mechanisms by which some androgenized ewes
      can produce normal reproductive cycles in the apparent absence of estrogen
      positive feedback are currently unknown.

PMID- 15509729
TI  - Testosterone stimulates follicle-stimulating hormone beta transcription via
      activation of extracellular signal-regulated kinase: evidence in rat pituitary
      cells.
AB  - This study investigated whether estradiol (E2) or testosterone (T) activate
      extracellular signal-regulated kinase (ERK) and calcium/calmodulin-dependent
      kinase II (Ca/CaMK II), as indicated by enzyme phosphorylation in rat
      pituitaries. In vivo studies used adult female rats given E2, T, or empty
      silastic capsules (vehicle controls). Twenty-four hours later, the rats were
      given a single pulse of GnRH (300 ng) or BSA-saline (to controls) and killed 5
      min later. GnRH stimulated a two- to three-fold rise in activated Ca/CaMK II, and
      E2 and T had no effect on Ca/CaMK II activation. In contrast, both GnRH and T
      stimulated threefold increases in ERK activity, with additive effects seen
      following the combination of GnRH+T. E2 had no effect on ERK activity. In alpha
      T3 clonal gonadotrope cells, dihydrotestosterone did not activate ERK alone but
      enhanced and prolonged the ERK responses to GnRH, demonstrating direct effects on
      the gonadotrope. Thus, the ERK response to GnRH plus androgen was enhanced in
      both rat pituitary and alpha T3 cells. In vitro studies with cultured rat
      pituitary cells examined the effect of GnRH+/-T in the presence of the mitogen
      activated protein (MAP) kinase kinase inhibitor, PD-098059 (PD). Results showed
      that PD suppressed ERK activational and FSH beta transcriptional responses to T.
      These findings suggest that one site of T regulation of FSH beta transcription is
      through the selective stimulation of the ERK pathway.

PMID- 15509730
TI  - Functional role of caspases in heat-induced testicular germ cell apoptosis.
AB  - In the present study, we determined whether a pan caspase inhibitor could prevent
      or attenuate heat-induced germ cell apoptosis. Groups of five adult (8 wk old)
      C57BL/6 mice pretreated with vehicle (DMSO) or Quinoline-Val-Asp (Ome)-CH2-O-Ph
      (Q-VD-OPH), a new generation broad-spectrum caspase inhibitor, were exposed once
      to local testicular heating (43 degrees C for 15 min) and killed 6 h later. The
      inhibitor (40 mg/kg body weight) or vehicle was administered intraperitoneally
      (i.p.) 1 h before local testicular heating. Germ cell apoptosis was detected by
      TUNEL assay and quantitated as number of apoptotic germ cells per 100 Sertoli
      cells at stages XI-XII. Compared with controls (16.8 +/- 3.1), mild testicular
      hyperthermia within 6 h resulted in a marked activation (277.3 +/- 21.6) of germ
      cell apoptosis, as previously reported by us. Q-VD-OPH at this dose markedly
      inhibited caspase 3 activation and significantly prevented (by 67.0%) heat
      induced germ cell apoptosis. Q-VD-OPH-mediated rescue of germ cells was
      independent of cytosolic translocation of mitochondrial cytochrome c and DIABLO.
      Electron microscopy further revealed normal appearance of these rescued cells.
      Similar protection from heat-induced germ cell apoptosis was also noted after
      pretreatment with minocycline, a second-generation tetracycline that effectively
      inhibits cytochrome c release and, in turn, caspase activation. Collectively, the
      present study emphasizes the role of caspases in heat-induced germ cell
      apoptosis.

PMID- 15509731
TI  - Human myometrial gene expression before and during parturition.
AB  - Identification of temporal and spatial changes in myometrial gene expression
      during parturition may further the understanding of the coordinated regulation of
      myometrial contractions during parturition. The objective of this study was to
      compare the gene expression profiles of human fundal myometrium from pregnant
      women before and after the onset of labor using a functional genomics approach,
      and to further characterize the spatial and temporal expression patterns of three
      genes believed to be important in parturition. Fundal myometrial mRNA was
      isolated from five women in labor and five women not in labor, and analyzed using
      human UniGEM-V microarrays with 9182 cDNA elements. Real-time polymerase chain
      reaction using myometrial RNA from pregnant women in labor or not in labor was
      used to examine mRNA levels for three of the genes; namely, prostaglandin
      endoperoxide synthase 2 (PTGS2), calgranulin B (S100A9), and oxytocin receptor
      (OXTR). The spatial expression pattern of these genes throughout the pregnant
      uterus before and after labor was also determined. Immunolocalization of
      cyclooxygenase-2 (also known as PTGS2) and S100A9 within the uterine cervix and
      myometrium were analyzed by immunohistochemistry. Few genes were differentially
      expressed in fundal myometrial tissues at term with the onset of labor. However,
      there appears to be a subset of genes important in the parturition cascade. The
      cellular properties of S100A9, its spatial localization, and dramatic increase in
      cervix and myometrium of women in labor suggest that this protein may be very
      important in the initiation or propagation of human labor.

PMID- 15509732
TI  - Identification of a new, testis-specific sperm antigen localized on the principal
      piece of the spermatozoa tail in the fox (Vulpes vulpes).
AB  - Fox (Vulpes vulpes) sperm antigens were identified to assess them as a potential
      target for a contraceptive vaccine. We report here the cloning and sequencing of
      fSP13, a fox sperm protein of 97 kDa. The fSP13 protein was both auto- and iso
      antigenic in foxes; it was recognized by sera of foxes immunized with fox sperm
      proteins and vasectomized foxes. The NH2-terminal sequence of fSP13 was
      determined, and a piece of cDNA was amplified from testicular RNA by reverse
      transcription polymerase chain reaction. This piece was used to screen a cDNA
      library from fox testis by Southern blot. A sequence of 1662 base pairs was
      obtained, including a major open reading frame coding for 498 amino acid. Mass
      spectrometry analysis confirmed the position of the open reading frame and the
      presence of posttranscriptional modifications. Analysis of the predicted amino
      acid sequence revealed no apparent transmembrane regions. Comparison of the
      protein sequence with the Prosite database demonstrated the presence of four
      potential N-linked glycosylation sites. The fSP13 bears the closest amino acid
      similarity to two human sperm proteins: fibrousheathin 2 and testis-specific
      calcium binding protein 86-VII. The deduced 80 N-terminal amino acid sequence
      also presents similarity with the RIIalpha domain. By using a serum against
      fSP13, this antigen was localized on the principal piece of the fox spermatozoa.
      Northern blot analysis showed that fSP13 is specifically expressed in testis. The
      fSP13 is one of the first fox sperm antigens to be cloned and sequenced.

PMID- 15509733
TI  - Extrasynaptic localization of inactivating calcium-activated potassium channels
      in mouse inner hair cells.
AB  - Auditory hair cells from nonmammalian vertebrates are electrically tuned to
      specific sound frequencies primarily by the interactions of voltage-gated calcium
      channels and calcium-activated potassium (BK) channels colocalized at synaptic
      active zones. Mammalian inner hair cells are not electrically tuned and, yet, BK
      channels are also thought to reside at active zones. Using patch-clamp recordings
      and immunofluorescence, we characterized BK channel expression in mouse inner
      hair cells. Unexpectedly, these channels have inactivating currents and are
      clustered near the apex of the cell away from synaptic sites near the base. These
      results indicate a novel function of BK channels in mammalian inner hair cells
      and provide a framework for future research.

PMID- 15509734
TI  - Asymmetrical modes of visual bottom-up and top-down integration in the thalamic
      nucleus rotundus of pigeons.
AB  - The aim of this study was to separate bottom-up and top-down influences within
      cerebral asymmetries. This was studied in the lateralized visual system of
      pigeons by recording from single units of the left and right diencephalic nucleus
      rotundus of the tectofugal pathway while visually stimulating the ipsilateral
      and/or contralateral eye. Analyses of response latencies revealed rotundal
      neurons with short and/or late response components. Cells with short latencies
      very likely represent bottom-up neurons participating in the ascending
      retinotectorotundal system. Because lidocaine injections into the visual Wulst
      produced a significant reduction of late response components only, neurons with
      long latencies were probably activated via a top-down telencephalotectorotundal
      system. The distribution and response characteristics of bottom-up and top-down
      neurons provided insight into several asymmetries of ascending and descending
      pathways. Asymmetries of the ascending retinotectorotundal system (bottom-up)
      were characterized by longer periods of tonic activation in the left and shorter
      response latencies in the right rotundus. Left-right differences in these
      responses probably facilitate faster access to visual input to the right
      hemisphere and a prolonged processing of this input in the left. The descending
      telencephalotectorotundal system (top-down) revealed a completely different
      lateralized organization. This system was characterized by long latency responses
      that exclusively derived from the left hemisphere, regardless of whether
      recordings took place in the left or the right rotundus. We assume that
      asymmetrical modes of visual processing within both hemispheres of the ascending
      tectofugal system are ultimately directed to left hemispheric forebrain
      mechanisms that subsequently generate executive control over sensory and motor
      structures.

PMID- 15509735
TI  - Neurofilament transport is dependent on actin and myosin.
AB  - Real-time analyses have revealed that some newly synthesized neurofilament (NF)
      subunits translocate into and along axonal neurites by moving along the inner
      plasma membrane surface, suggesting that they may translocate against the
      submembrane actin cortex. We therefore examined whether or not NF axonal
      transport was dependent on actin and myosin. Perturbation of filamentous actin in
      NB2a/d1 cells with cytochalasin B inhibited translocation of subunits into axonal
      neurites and inhibited bidirectional translocation of NF subunits within
      neurites. Intravitreal injection of cytochalasin B inhibited NF axonal transport
      in optic axons in a dose-response manner. NF subunits were coprecipitated from
      NB2a/d1 cells by an anti-myosin antibody, and myosin colocalized with NFs in
      immunofluorescent analyses. The myosin light chain kinase inhibitor ML-7 and the
      myosin ATPase inhibitor 2,3-butanedione-2-monoxime perturbed NF translocation
      within NB2a/d1 axonal neurites. These findings suggest that some NF subunits may
      undergo axonal transport via myosin-mediated interactions with the actin cortex.

PMID- 15509736
TI  - Fibroblast growth factor receptor signaling promotes radial glial identity and
      interacts with Notch1 signaling in telencephalic progenitors.
AB  - The Notch and fibroblast growth factor (FGF) pathways both regulate cell fate
      specification during mammalian neural development. We have shown previously that
      Notch1 activation in the murine forebrain promotes radial glial identity. This
      result, together with recent evidence that radial glia can be progenitors,
      suggested that Notch1 signaling might promote progenitor and radial glial
      character simultaneously. Consistent with this idea, we found that in addition to
      promoting radial glial character in vivo, activated Notch1 (ActN1) increased the
      frequency of embryonic day 14.5 (E14.5) ganglionic eminence (GE) progenitors that
      grew into neurospheres in FGF2. Constitutive activation of C-promoter binding
      factor (CBF1), a Notch pathway effector, also increased neurosphere frequency in
      FGF2, suggesting that the effect of Notch1 on FGF responsiveness is mediated by
      CBF1. The observation that ActN1 promoted FGF responsiveness in telencephalic
      progenitors prompted us to examine the effect of FGF pathway activation in vivo.
      We focused on FGFR2 because it is expressed in radial glia in the GEs where ActN1
      increases FGF2 neurosphere frequency, but not in the septum where it does not.
      Like ActN1, activated FGFR2 (ActFGFR2) promoted radial glial character in vivo.
      However, unlike ActN1, ActFGFR2 did not enhance neurosphere frequency at E14.5.
      Additional analysis demonstrated that, unexpectedly, neither ActFGFR2 nor
      ActFGFR1 could replace the need for ligand in promoting neurosphere
      proliferation. This study suggests that telencephalic progenitors with radial
      glial morphology are maintained by interactions between the Notch and FGF
      pathways, and that the mechanisms by which FGF signaling promotes radial glial
      character in vivo and progenitor proliferation in vitro can be uncoupled.

PMID- 15509737
TI  - Heterosynaptic long-term potentiation of inhibitory interneurons in the lateral
      amygdala.
AB  - Long-term potentiation (LTP) of synaptic transmission in the lateral amygdala
      (LA) is believed to underlie the formation and retention of fear memories. To
      explore the role of inhibitory transmission in amygdala plasticity, we recorded
      from LA inhibitory interneurons in vitro before and after tetanization of the
      thalamo-LA pathway, one of the major inputs to LA involved in fear learning.
      Tetanization resulted in LTP of the EPSPs elicited in both the tetanized thalamic
      pathway and the untetanized cortical pathway to LA. This LTP was NMDA-dependent
      and associated with a decrease in paired-pulse facilitation in both pathways. In
      LA excitatory cells, LTP of interneurons resulted in an increase in the amplitude
      of GABAergic IPSPs in both input pathways. Finally, isolated GABAergic IPSPs
      between inhibitory and excitatory neurons could be potentiated as well.
      Plasticity of inhibitory transmission within the LA may therefore contribute
      significantly to LA-mediated functions, such as fear conditioning.

PMID- 15509738
TI  - Cross talk between metabotropic and ionotropic glutamate receptor-mediated
      signaling in parallel fiber-induced inositol 1,4,5-trisphosphate production in
      cerebellar Purkinje cells.
AB  - In many excitatory glutamatergic synapses, both ionotropic glutamate receptors
      (iGluRs) and metabotropic glutamate receptors (mGluRs) are closely distributed on
      the postsynaptic membrane. However, the functional significance of the close
      distribution of the two types of glutamate receptors has not been fully
      clarified. In this study, we examined the functional interaction between iGluR
      and mGluR at parallel fiber (PF)--> Purkinje cell synapses in the generation of
      inositol 1,4,5-trisphosphate (IP3), a key second messenger that regulates many
      important cellular functions. We visualized local IP3 dynamics in Purkinje cells
      using the green fluorescent protein-tagged pleckstrin homology domain (GFP-PHD)
      as a fluorescent IP3 probe. Purkinje cells were transduced with Sindbis virus
      encoding GFP-PHD and imaged with a two-photon laser scanning microscope.
      Translocation of GFP-PHD from the plasma membrane to the cytoplasm attributable
      to an increase in IP3 concentration was observed on PF stimulation in fine
      dendrites of Purkinje cells. Surprisingly, this PF-induced IP3 production was
      blocked not only by the group I mGluR antagonist but also by the AMPA receptor
      (AMPAR) antagonist. The PF-induced IP3 production was blocked by either the
      inhibition of G-protein activation by GDP-betaS or intracellular Ca2+ buffering
      by BAPTA. These results show that IP3 production is mediated cooperatively by
      group I mGluR and AMPAR through G-protein activation and Ca2+ influx at PF-->
      Purkinje cell synapses, identifying the robust cross talk between iGluR and mGluR
      for the generation of IP3 signals.

PMID- 15509739
TI  - TRPV1 function in mouse colon sensory neurons is enhanced by metabotropic 5
      hydroxytryptamine receptor activation.
AB  - Using whole-cell patch-clamp methods, we examined the hypothesis that serotonin
      [5-hydroxytryptamine (5-HT)] receptor activation enhances TRPV1 function in mouse
      colon sensory neurons in lumbosacral dorsal root ganglia, which were identified
      by retrograde labeling with DiI (1,1'-dioctadecyl-3,3,3',3
      tetramethlindocarbocyanine methanesulfonate) injected into multiple sites in the
      wall of the descending colon. 5-HT increased membrane excitability at a
      temperature below body temperature in response to thermal ramp stimuli in colon
      sensory neurons from wild-type mice, but not from TRPV1 knock-out mice. 5-HT
      significantly enhanced capsaicin-, heat-, and proton-evoked currents with an EC50
      value of 2.2 microm. 5-HT (1 microm) significantly increased capsaicin-evoked
      (100 nm) and proton-evoked (pH 5.5) currents 1.6- and 4.7-fold, respectively, and
      significantly decreased the threshold temperature for heat current activation
      from 42 to 38 degrees C. The enhancement of TRPV1 by 5-HT was significantly
      attenuated by selective 5-HT2 and 5-HT4 receptor antagonists, but not by a 5-HT3
      receptor antagonist. In support, 5-HT2 and 5-HT4 receptor agonists mimicked the
      facilitating effects of 5-HT on TRPV1 function. Downstream signaling required G
      protein activation and phosphorylation as intracellularly administered GDP-beta-S
      [guanosine 5'-O-(2-thiodiphosphate], protein kinase A inhibitors, and an A-kinase
      anchoring protein inhibitor significantly blocked serotonergic facilitation of
      TRPV1 function; 5-HT2 receptor-mediated facilitation was also inhibited by a PKC
      inhibitor. We conclude that the facilitation of TRPV1 by metabotropic 5-HT
      receptor activation may contribute to hypersensitivity of primary afferent
      neurons in irritable bowel syndrome patients.

PMID- 15509740
TI  - Human immunodeficiency virus type 1 gp120 induces apoptosis in human primary
      neurons through redox-regulated activation of neutral sphingomyelinase.
AB  - Human immunodeficiency virus type 1 (HIV-1) infection is known to cause disorders
      of the CNS, including HIV-associated dementia (HAD). HIV-1 coat protein gp120
      (glycoprotein 120) induces neuronal apoptosis and has been implicated in the
      pathogenesis of HAD. However, the mechanism by which gp120 causes neuronal
      apoptosis is poorly understood. The present study underlines the importance of
      gp120 in inducing the production of ceramide, an important inducer of apoptosis,
      in human primary neurons. gp120 induced the activation of sphingomyelinases
      (primarily the neutral one) and the production of ceramide in primary neurons.
      Antisense knockdown of neutral (NSMase) but not acidic (ASMase) sphingomyelinase
      markedly inhibited gp120-mediated apoptosis and cell death of primary neurons,
      suggesting that the activation of NSMase but not ASMase plays an important role
      in gp120-mediated neuronal apoptosis. Similarly, the HIV-1 regulatory protein Tat
      also induced neuronal cell death via NSMase. Furthermore, gp120-induced
      production of ceramide was redox sensitive, because reactive oxygen species were
      involved in the activation of NSMase but not ASMase. gp120 coupled CXCR4 (CXC
      chemokine receptor 4) to induce NADPH oxidase-mediated production of superoxide
      radicals in neurons, which was involved in the activation of NSMase but not
      ASMase. These studies suggest that gp120 may induce neuronal apoptosis in the CNS
      of HAD patients through the CXCR4-NADPH oxidase-superoxide-NSMase-ceramide
      pathway.

PMID- 15509741
TI  - Dopamine modulates release from corticostriatal terminals.
AB  - Normal striatal function is dependent on the availability of synaptic dopamine to
      modulate neurotransmission. Within the striatum, excitatory inputs from cortical
      glutamatergic neurons and modulatory inputs from midbrain dopamine neurons
      converge onto dendritic spines of medium spiny neurons. In addition to dopamine
      receptors on medium spiny neurons, D2 receptors are also present on
      corticostriatal terminals, where they act to dampen striatal excitation. To
      determine the effect of dopamine depletion on corticostriatal activity, we used
      the styryl dye FM1-43 in combination with multiphoton confocal microscopy in
      slice preparations from dopamine-deficient (DD) and reserpine-treated mice. The
      activity-dependent release of FM1-43 out of corticostriatal terminals allows a
      measure of kinetics quantified by the halftime decay of fluorescence intensity.
      In DD, reserpine-treated, and control mice, exposure to the D2-like receptor
      agonist quinpirole revealed modulation of corticostriatal kinetics with
      depression of FM1-43 destaining. In DD and reserpine-treated mice, quinpirole
      decreased destaining to a greater extent, and at a lower dose, consistent with
      hypersensitive corticostriatal D2 receptors. Compared with controls, slices from
      DD mice did not react to amphetamine or to cocaine with dopamine-releasing
      striatal stimulation unless the animals were pretreated with l-3,4
      dihydroxyphenylalanine (l-dopa). Electron microscopy and immunogold labeling for
      glutamate terminals within the striatum demonstrated that the observed
      differences in kinetics of corticostriatal terminals in DD mice were not
      attributable to aberrant cytoarchitecture or glutamate density. Microdialysis
      revealed that basal extracellular striatal glutamate was normal in DD mice. These
      data indicate that dopamine deficiency results in morphologically normal
      corticostriatal terminals with hypersensitive D2 receptors.

PMID- 15509742
TI  - Mapping dopamine function in primates using pharmacologic magnetic resonance
      imaging.
AB  - Dopamine (DA) receptors play a central role in such diverse pathologies as
      Parkinson's disease, schizophrenia, and drug abuse. We used an amphetamine
      challenge combined with pharmacologic magnetic resonance imaging (phMRI) to map
      DA-associated circuitry in nonhuman primates with high sensitivity and spatial
      resolution. Seven control cynomolgous monkeys and 10 MPTP (1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine)-treated parkinsonian primates were studied
      longitudinally using both positron emission tomography (PET) and phMRI.
      Amphetamine challenge (2.5 mg/kg, i.v.) in control monkeys increased relative
      cerebral blood volume (rCBV) in a number of brain regions not described
      previously, such as parafascicular thalamus, precentral gyrus, and dentate
      nucleus of the cerebellum. With the high spatial resolution, we were also able to
      readily identify changes in rCBV in the anterior cingulate, substantia nigra,
      ventral tegmental area, caudate (tail and head), putamen, and nucleus accumbens.
      Amphetamine induced decreases in rCBV in occipital and posterior parietal
      cortices. Parkinsonian primates had a prominent loss of response to amphetamine,
      with relative sparing of the nucleus accumbens and parafascicular thalamus. There
      was a significant correlation between rCBV loss in the substantia nigra and both
      PET imaging of dopamine transporters and behavioral measures. Monkeys with
      partial lesions as defined by 2beta-carbomethoxy-3beta-(4-fluorophenyl) tropane
      binding to dopamine transporters showed recruitment of premotor and motor cortex
      after amphetamine stimulus similar to what has been noted in Parkinson's patients
      during motor tasks. These data indicate that phMRI is a powerful tool for
      assessment of dynamic changes associated with normal and dysfunctional DA brain
      circuitry in primates.

PMID- 15509743
TI  - Metamodulation of a spinal locomotor network by nitric oxide.
AB  - Flexibility in the output of spinal networks can be accomplished by the actions
      of neuromodulators; however, little is known about how the process of
      neuromodulation itself may be modulated. Here we investigate the potential "meta"
      modulatory hierarchy between nitric oxide (NO) and noradrenaline (NA) in Xenopus
      laevis tadpoles. NO and NA have similar effects on fictive swimming; both
      potentiate glycinergic inhibition to slow swimming frequency and GABAergic
      inhibition to reduce episode durations. In addition, both modulators have direct
      effects on the membrane properties of motor neurons. Here we report that
      antagonism of noradrenergic pathways with phentolamine dramatically influences
      the effect of the NO donor S-nitroso-N-acetylpenicillamine (SNAP) on swimming
      frequency, but not its effect on episode durations. In contrast, scavenging
      extracellular NO with 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3
      oxide (PTIO) does not influence any of the effects of NA on fictive swimming.
      These data place NO above NA in the metamodulatory hierarchy, strongly suggesting
      that NO works via a noradrenergic pathway to control glycine release but directly
      promotes GABA release. We confirmed this possibility using intracellular
      recordings from motor neurons. In support of a natural role for NO in the Xenopus
      locomotor network, PTIO not only antagonized all of the effects of SNAP on
      swimming but also, when applied on its own, modulated both swimming frequency and
      episode durations in addition to the underlying glycinergic and GABAergic
      pathways. Collectively, our results illustrate that NO and NA have parallel
      effects on motor neuron membrane properties and GABAergic inhibition, but that NO
      serially metamodulates glycinergic inhibition via NA.

PMID- 15509744
TI  - Monitoring neural activity and [Ca2+] with genetically encoded Ca2+ indicators.
AB  - Genetically encoded Ca2+ indicators (GECIs) based on fluorescent proteins (XFPs)
      and Ca2+-binding proteins [like calmodulin (CaM)] have great potential for the
      study of subcellular Ca2+ signaling and for monitoring activity in populations of
      neurons. However, interpreting GECI fluorescence in terms of neural activity and
      cytoplasmic-free Ca2+ concentration ([Ca2+]) is complicated by the nonlinear
      interactions between Ca2+ binding and GECI fluorescence. We have characterized
      GECIs in pyramidal neurons in cultured hippocampal brain slices, focusing on
      indicators based on circularly permuted XFPs [GCaMP (Nakai et al., 2001),
      Camgaroo2 (Griesbeck et al., 2001), and Inverse Pericam (Nagai et al., 2001)].
      Measurements of fluorescence changes evoked by trains of action potentials
      revealed that GECIs have little sensitivity at low action potential frequencies
      compared with synthetic [Ca2+] indicators with similar affinities for Ca2+. The
      sensitivity of GECIs improved for high-frequency trains of action potentials,
      indicating that GECIs are supralinear indicators of neural activity. Simultaneous
      measurement of GECI fluorescence and [Ca2+] revealed supralinear relationships.
      We compared GECI fluorescence saturation with CaM Ca2+-dependent structural
      transitions. Our data suggest that GCaMP and Camgaroo2 report CaM structural
      transitions in the presence and absence of CaM-binding peptide, respectively.

PMID- 15509745
TI  - Visual experience is necessary for the development of multisensory integration.
AB  - Multisensory neurons and their ability to integrate multisensory cues develop
      gradually in the midbrain [i.e., superior colliculus (SC)]. To examine the
      possibility that early sensory experiences might play a critical role in these
      maturational processes, animals were raised in the absence of visual cues. As
      adults, the SC of these animals were found to contain many multisensory neurons,
      the large majority of which were visually responsive. Although these neurons
      responded robustly to each of their cross-modal inputs when presented
      individually, they were incapable of synthesizing this information. These
      observations suggest that visual experiences are critical for the SC to develop
      the ability to integrate multisensory information and lead to the prediction
      that, in the absence of such experience, animals will be compromised in their
      sensitivity to cross-modal events.

PMID- 15509746
TI  - Na-K-Cl cotransporter-mediated intracellular Na+ accumulation affects Ca2+
      signaling in astrocytes in an in vitro ischemic model.
AB  - Na-K-Cl cotransporter isoform 1 (NKCC1) plays an important role in maintenance of
      intracellular Na+, K+, and Cl- levels in astrocytes. We propose that NKCC1 may
      contribute to perturbations of ionic homeostasis in astrocytes under ischemic
      conditions. After 3-8 hr of oxygen and glucose deprivation (OGD), NKCC1-mediated
      86Rb influx was significantly increased in astrocytes from NKCC1 wild-type
      (NKCC1+/+) and heterozygous mutant (NKCC1+/-) mice. Phosphorylated NKCC1 protein
      was increased in NKCC1+/+ astrocytes at 2 hr of OGD. Two hours of OGD and 1 hr of
      reoxygenation (OGD/REOX) triggered an 3.6-fold increase in intracellular Na+
      concentration ([Na+]i) in NKCC1+/+ astrocytes. Inhibition of NKCC1 activity by
      bumetanide or ablation of the NKCC1 gene significantly attenuated the rise in
      [Na+]i. Moreover, NKCC1+/+ astrocytes swelled by 10-30% during 20-60 min of OGD.
      Either genetic ablation of NKCC1 or inhibition of NKCC1 by bumetanide-attenuated
      OGD-mediated swelling. An NKCC1-mediated increase in [Na+]i may subsequently
      affect Ca2+ signaling through the Na+/Ca2+ exchanger (NCX). A rise in [Ca2+]i was
      detected after OGD/REOX in the presence of a sarcoplasmic-endoplasmic reticulum
      (ER) Ca2+-ATPase inhibitor thapsigargin. Moreover, OGD/REOX led to a significant
      increase in Ca2+ release from ER Ca2+ stores. Furthermore, KB-R7943 (2-[2-[4(4
      nitrobenzyloxy)phenyl]ethyl]isothiourea mesylate), an inhibitor of reverse-mode
      operation of NCX, abolished the OGD/REOX-induced enhancement in filling of ER
      Ca2+ stores. OGD/REOX-mediated Ca2+ accumulation in ER Ca2+ stores was absent
      when NKCC1 activity was ablated or pharmacologically inhibited. These findings
      imply that stimulation of NKCC1 activity leads to Na+ accumulation after OGD/REOX
      and that subsequent reverse-mode operation of NCX contributes to increased Ca2+
      accumulation by intracellular Ca2+ stores.

PMID- 15509747
TI  - Experience and activity-dependent maturation of perisomatic GABAergic innervation
      in primary visual cortex during a postnatal critical period.
AB  - The neocortical GABAergic network consists of diverse interneuron cell types that
      display distinct physiological properties and target their innervations to
      subcellular compartments of principal neurons. Inhibition directed toward the
      soma and proximal dendrites is crucial in regulating the output of pyramidal
      neurons, but the development of perisomatic innervation is poorly understood
      because of the lack of specific synaptic markers. In the primary visual cortex,
      for example, it is unknown whether, and to what extent, the formation and
      maturation of perisomatic synapses are intrinsic to cortical circuits or are
      regulated by sensory experience. Using bacterial artificial chromosome transgenic
      mice that label a defined class of perisomatic synapses with green fluorescent
      protein, here we show that perisomatic innervation developed during a protracted
      postnatal period after eye opening. Maturation of perisomatic innervation was
      significantly retarded by visual deprivation during the third, but not the fifth,
      postnatal week, implicating an important role for sensory input. To examine the
      role of cortical intrinsic mechanisms, we developed a method to visualize
      perisomatic synapses from single basket interneurons in cortical organotypic
      cultures. Characteristic perisomatic synapses formed through a stereotyped
      process, involving the extension of distinct terminal branches and proliferation
      of perisomatic boutons. Neuronal spiking in organotypic cultures was necessary
      for the proliferation of boutons and the extension, but not the maintenance, of
      terminal branches. Together, our results suggest that although the formation of
      perisomatic synapses is intrinsic to the cortex, visual experience can influence
      the maturation and pattern of perisomatic innervation during a postnatal critical
      period by modulating the level of neural activity within cortical circuits.

PMID- 15509748
TI  - Calcium release from presynaptic ryanodine-sensitive stores is required for long
      term depression at hippocampal CA3-CA3 pyramidal neuron synapses.
AB  - Although Ca2+ release from internal stores has been proposed to be important for
      the induction of long-term synaptic plasticity, the importance of Ca2+ stores
      localized in presynaptic terminals remains unclear. Here, we have selectively
      applied pharmacological antagonists to either the presynaptic or postsynaptic
      cell in paired whole-cell recordings from hippocampal CA3 pyramidal neurons in
      slice culture. We demonstrate directly the necessary role of presynaptic, but not
      postsynaptic, ryanodine-sensitive Ca2+ stores in the induction of NMDA receptor
      (NMDAR)-dependent long-term depression (LTD). Using two-photon laser scanning
      microscopy, we further find that release from the ryanodine-sensitive stores
      during prolonged synaptic stimulation generates a slowly rising Ca2+ signal in
      the presynaptic terminal that is required for the induction of LTD. Moreover,
      this form of LTD has a significant presynaptic component of expression because it
      causes a marked decrease in the rate of release from CA3 neuron presynaptic
      terminals of FM 1-43, a fluorescent probe of synaptic vesicle cycling. Thus, Ca2+
      release from presynaptic ryanodine-sensitive stores is critical in the induction
      of a presynaptic component of NMDAR-dependent LTD.

PMID- 15509749
TI  - Cell-specific expression and lipopolysaccharide-induced regulation of tumor
      necrosis factor alpha (TNFalpha) and TNF receptors in rat dorsal root ganglion.
AB  - The proinflammatory and lipopolysaccharide (LPS)-inducible cytokine tumor
      necrosis factor alpha (TNFalpha) has been shown to enhance primary sensory
      nociceptive signaling. However, the precise cellular sites of TNFalpha and TNF
      receptor synthesis are still a matter of controversy. Therefore, we
      differentiated the neuronal and non-neuronal sites of TNFalpha, TNFR1, and TNFR2
      mRNA synthesis in dorsal root ganglion (DRG) of control rats and evaluated how
      their expression is altered under systemic challenge with LPS. In situ
      hybridization (ISH), RT-PCR analysis of laser-microdissected cells, and
      immunocytochemistry revealed absence of TNFalpha from DRG neurons and LPS-induced
      expression of TNFalpha exclusively in a subpopulation of non-neuronal DRG cells.
      Using RT-PCR and Northern blotting TNFR1 and TNFR2 mRNAs were found to be
      constitutively expressed and increased after LPS. TNFR1 mRNA was expressed in
      virtually all neurons and in non-neuronal cells with increased levels after LPS
      in both. TNFR2 was exclusively expressed and regulated in non-neuronal cells. RT
      PCR analysis of microdissected DRG neurons and of the sensory neuronal cell line
      F11 confirmed the neuronal expression of TNFR1 and excluded that of TNFR2. Double
      ISH revealed varying levels of TNFR1 mRNA in virtually all DRG neurons including
      putative nociceptive neurons coding for calcitonin gene-related peptide,
      substance P, or vanilloid receptor 1. Taken together, we provide evidence that
      non-neuronally synthesized TNFalpha may directly act on primary afferent neurons
      via TNFR1 but not TNFR2. This is likely to be relevant under conditions of
      inflammatory pain and infections accompanied by widespread TNFalpha synthesis and
      release and may drive sickness behavior.

PMID- 15509750
TI  - Brain insulin impairs amyloid-beta(1-40) clearance from the brain.
AB  - Cerebral amyloid-beta peptide (Abeta) clearance plays a key role in determining
      the brain level of Abeta; however, its mechanism remains unclear. In this study,
      we investigated cerebral Abeta clearance across the blood-brain barrier (BBB) by
      using the Brain Efflux Index method. [125I]Abeta(1-40) was eliminated from rat
      brain to circulating blood with a half-life of 48.8 min and a half-saturation
      concentration of 8.15 nm. The Abeta(1-40) elimination rate was reduced by 30.5%
      in 23-month-old rats compared with 7-week-old rats. The intact form of Abeta(1
      40) was detected in plasma after intracerebral administration, indicating the
      occurrence of efflux transport of intact Abeta(1-40). The Abeta(1-40) elimination
      rate was significantly inhibited by coadministration of 100 microg/ml insulin and
      1 mm thiorphan by 44.6 and 34.0%, respectively. The level of intact [125I]Abeta(1
      40) in the brain was increased by coadministration of insulin. Among insulin
      degrading enzyme inhibitors, bacitracin inhibited the elimination rate, whereas N
      ethylmaleimide and metal chelators had no effect. Receptor-associated protein,
      fucoidan, 3-bromo-5-t-butyl-4-hydroxy-benzylidenemalonitrile, anti-IGF-I receptor
      antibody, and l-tyrosine did not affect the Abeta(1-40) elimination rate,
      suggesting that the relevant receptors or transporters are not likely to be
      involved in the clearance. In conclusion, the present study has demonstrated the
      involvement of a proteolytic degradation process and an insulin-sensitive process
      in cerebral Abeta(1-40) clearance in the rat.

PMID- 15509751
TI  - The invulnerability of adult neurons: a critical role for p73.
AB  - Here, we investigated the intracellular mechanisms that underlie the relative
      invulnerability of adult versus developing dorsal root ganglion (DRG) sensory
      neurons. In culture, adult neurons were resistant to stimuli that caused
      apoptosis of their neonatal counterparts. In both adult and neonatal neurons,
      death stimuli induced the apoptotic c-Jun N-terminal protein kinase (JNK)
      pathway, but JNK activation only caused death of neonatal neurons, indicating
      that adult neurons have a downstream block to apoptosis. Expression of the
      dominant-inhibitory p53 family member, DeltaNp73, rescued JNK-induced apoptosis
      of neonatal neurons, suggesting that it might participate in the downstream
      apoptotic block in adult neurons. To test this possibility, we examined adult DRG
      neurons cultured from p73+/- mice. Adult p73+/- DRG neurons were more vulnerable
      to apoptotic stimuli than their p73+/+ counterparts, and invulnerability could be
      restored to the p73+/- neurons by increased expression of DeltaNp73. Moreover,
      although DRG neuron development was normal in p73+/- animals in vivo, axotomy
      caused death of adult p73+/- but not p73+/+ DRG neurons. Thus, one way adult
      neurons become invulnerable is to enhance endogenous survival pathways, and one
      critical component of these survival pathways is p73.

PMID- 15509752
TI  - Filamin A and FILIP (Filamin A-Interacting Protein) regulate cell polarity and
      motility in neocortical subventricular and intermediate zones during radial
      migration.
AB  - In the developing neocortex, most excitatory neurons are supplied and arranged
      through radial migration. Because neurons show global morphological changes and
      complicated behavior during that migration, precise regulation of cell shape and
      polarity is essential for proper migration and correct neocortical formation;
      however, how cell shape and polarity are regulated in migrating neuron remains
      elusive. We show here that Filamin A, a well known actin-binding protein,
      determines the shape of neocortical neurons during radial migration in vivo.
      Dysfunction of Filamin A, caused by a mutant Filamin A expression, prevents cells
      from acquiring consistent polarity toward specific direction and decreases
      motility in the subventricular and intermediate zones. In contrast, Filamin A
      overexpression, achieved by a short interfering RNA for Filamin A-interacting
      protein that induces Filamin A degradation (FILIP), promotes the development and
      maintenance of a bipolar shape also in the subventricular and intermediate zones.
      These results suggest that the amount of Filamin A helps migrating neurons
      determine their mode of migration, multipolar or bipolar, before entering the
      cortical plate and that FILIP is responsible, at least in part, for Filamin A
      content. In addition, our results also give a possible clue to understanding the
      pathogenesis of human malformation periventricular heterotopia, which is caused
      by various "loss-of-function" mutations in the filamin A gene.

PMID- 15509753
TI  - Distinct roles for the kainate receptor subunits GluR5 and GluR6 in kainate
      induced hippocampal gamma oscillations.
AB  - Kainate receptors (KARs) play an important role in synaptic physiology,
      plasticity, and pathological phenomena such as epilepsy. However, the
      physiological implications for neuronal networks of the distinct expression
      patterns of KAR subunits are unknown. Using KAR knock-out mice, we show that
      subunits glutamate receptor (GluR) 5 and GluR6 play distinct roles in kainate
      induced gamma oscillations and epileptiform burst activity. Ablation of GluR5
      leads to a higher susceptibility of the network to the oscillogenic and
      epileptogenic effects of kainate, whereas lack of GluR6 prevents kainate-induced
      gamma oscillations or epileptiform bursts. Based on experimental and simulated
      neuronal network data as well as the consequences of GluR5 and GluR6 expression
      for cellular and synaptic physiology, we propose that the functional interplay of
      GluR5-containing KARs on axons of interneurons and GluR6-containing KARs in the
      somatodendritic region of both interneurons and pyramidal cells underlie the
      oscillogenic and epileptogenic effects of kainate.

PMID- 15509754
TI  - Glutamate mediates acute glucose transport inhibition in hippocampal neurons.
AB  - Although it is known that brain activity is fueled by glucose, the identity of
      the cell type that preferentially metabolizes the sugar remains elusive. To
      address this question, glucose uptake was studied simultaneously in cultured
      hippocampal neurons and neighboring astrocytes using a real-time assay based on
      confocal epifluorescence microscopy and fluorescent glucose analogs. Glutamate,
      although stimulating glucose transport in astrocytes, strongly inhibited glucose
      transport in neurons, producing in few seconds a 12-fold increase in the ratio of
      astrocytic-to-neuronal uptake rate. Neuronal transport inhibition was reversible
      on removal of the neurotransmitter and displayed an IC50 of 5 microm, suggesting
      its occurrence at physiological glutamate concentrations. The phenomenon was
      abolished by CNQX and mimicked by AMPA, demonstrating a role for the cognate
      subset of ionotropic glutamate receptors. Transport inhibition required
      extracellular sodium and calcium and was mimicked by veratridine but not by
      membrane depolarization with high K+ or by calcium overloading with ionomycin.
      Therefore, glutamate inhibits glucose transport via AMPA receptor-mediated sodium
      entry, whereas calcium entry plays a permissive role. This phenomenon suggests
      that glutamate redistributes glucose toward astrocytes and away from neurons and
      represents a novel molecular mechanism that may be important for functional
      imaging of the brain using positron emission tomography.

PMID- 15509755
TI  - The effect of motor imagery on spinal segmental excitability.
AB  - The purpose of this study was to investigate the effect of motor imagery on
      spinal segmental excitability by recording the reflex responses to externally
      applied stretch of the extrinsic finger flexors and extensors during the
      performance of an imaginary task. Nine young healthy subjects performed a series
      of imagined flexion-extension movements of the fingers. Muscle stretch was
      imposed concurrently by applying rotations of the metacarpophalangeal joints at
      100, 300, or 500 degrees /sec. Three of the nine tested subjects also generated
      0.2 Newton meter voluntary flexion torque in preloading tasks before stretch. At
      300 degrees /sec stretch, electromyogram (EMG) and torque reflex responses, which
      were observed in the finger flexors in four of nine subjects during motor
      imagery, were activated at a short latency (38.6 +/- 10.6 msec). This latency was
      similar to that recorded during a stretch of preactivated flexor muscles (34.4 +/
      3.6 msec), in which motoneurons are already suprathreshold and in which
      monosynaptic effects of muscle afferents are likely to be discernable. In a
      similar manner, for stretches imposed at 500 degrees /sec, responses to stretch
      of the flexors were observed in all five tested subjects in imaginary flexion
      tasks at very short latencies (26.4 +/- 3.7 msec), again similar to those induced
      by tendon taps (22.8 +/- 1.2 msec). No EMG response was observed at rest during
      stretches. These observations support the view that effects must have been
      mediated by imagery-related subthreshold activation of spinal motoneurons and/or
      interneurons, rather than by long-latency transcortical reflex responses. We
      conclude that motor imagery has a potent effect on the excitability of spinal
      reflex pathways.

PMID- 15509756
TI  - Cell type-specific synaptic dynamics of synchronized bursting in the juvenile CA3
      rat hippocampus.
AB  - Spontaneous synchronous bursting of the CA3 hippocampus in vitro is a widely
      studied model of physiological and pathological network synchronization. The role
      of inhibitory conductances during network bursting is not understood in detail,
      despite the fact that several antiepileptic drugs target GABA(A) receptors. Here,
      we show that the first manifestation of a burst event is a cell type-specific
      flurry of GABA(A) receptor-mediated inhibitory input to pyramidal cells, but not
      to stratum oriens horizontal interneurons. Moreover, GABA(A) receptor-mediated
      synaptic input is proportionally smaller in these interneurons compared with
      pyramidal cells. Computational models and dynamic-clamp studies using
      experimentally derived conductance waveforms indicate that both these factors
      modulate spike timing during synchronized activity. In particular, the different
      kinetics and the larger strength of GABAergic input to pyramidal cells defer
      action potential initiation and contribute to the observed delay of firing, so
      that the interneuronal activity leads the burst cycle. In contrast, excitatory
      inputs to both neuronal populations during a burst are kinetically similar, as
      required to maintain synchronicity. We also show that the natural pattern of
      activation of inhibitory and excitatory conductances during a synchronized burst
      cycle is different within the same neuronal population. In particular, GABA(A)
      receptor-mediated currents activate earlier and outlast the excitatory components
      driving the bursts. Thus, cell type-specific balance and timing of GABA(A)
      receptor-mediated input are critical to set the appropriate spike timing in
      pyramidal cells and interneurons and coordinate additional neurotransmitter
      release modulating burst strength and network frequency.

PMID- 15509757
TI  - Classical photoreceptors regulate melanopsin mRNA levels in the rat retina.
AB  - Recent studies have demonstrated that melanopsin is a key photopigment in the
      mammalian circadian system. This novel opsin is exclusively expressed in retinal
      ganglion cells that are intrinsically sensitive to light, perhaps responding via
      a melanopsin-based signaling pathway. Previous investigations using transgenic
      mice have also demonstrated that ablation of the classical photoreceptors and of
      melanopsin prevents entrainment of several circadian rhythms, thus demonstrating
      that these photoreceptors are necessary and sufficient for circadian
      photoreception. In this study, we investigated the effect of photoreceptor
      degeneration on melanopsin mRNA regulation in RCS/N-rdy rats (Royal College of
      Surgeons rats with a defect in the retinal dystrophy gene). We used animals at
      postnatal day 21 (P21), P33, P45, and P60. At P60 degeneration of the retina in
      RCS/N-rdy has advanced to the point where the majority of the photoreceptors have
      degenerated. Our data indicate that melanopsin mRNA levels were rhythmic in
      light/dark cycle and in constant darkness in congenic controls (RCS/N-rdy+) and
      in RCS/N-rdy at P21 (i.e., before the degeneration of the photoreceptors). On the
      other hand, in RCS/N-rdy at P60, melanopsin mRNA levels were greatly reduced
      (<90%) and not rhythmic. Photoreceptor degeneration did not affect the expression
      of pituitary adenylate cyclase-activating polypeptide mRNA (a marker for
      melanopsin-containing ganglion cells). Our results suggest that classical
      photoreceptors (rods and cones) regulate the expression of melanopsin mRNA in the
      rat. Because RCS/N-rdy rats are a model for studies on retinitis pigmentosa in
      human, our data may provide an important insight on melanopsin function in
      patients affected by retinitis pigmentosa.

PMID- 15509758
TI  - Enhanced accuracy in novel mirror drawing after repetitive transcranial magnetic
      stimulation-induced proprioceptive deafferentation.
AB  - When performing visually guided actions under conditions of perturbed visual
      feedback, e.g., in a mirror or a video camera, there is a spatial conflict
      between visual and proprioceptive information. Recent studies have shown that
      subjects without proprioception avoid this conflict and show a performance
      benefit. In this study, we tested whether deafferentation induced by repetitive
      transcranial magnetic stimulation (rTMS) can improve mirror tracing skills in
      normal subjects. Hand trajectory error during novel mirror drawing was compared
      across two groups of subjects that received either 1 Hz rTMS over the
      somatosensory cortex contralateral to the hand or sham stimulation. Mirror
      tracing was more accurate after rTMS than after sham stimulation. Using a
      position-matching task, we confirmed that rTMS reduced proprioceptive acuity and
      that this reduction was largest when the coil was placed at an anterior parietal
      site. It is thus possible, with rTMS, to enhance motor performance in tasks
      involving a visuoproprioceptive conflict, presumably by reducing the excitability
      of somatosensory cortical areas that contribute to the sense of hand position.

PMID- 15509759
TI  - Corticotropin-releasing hormone directly activates noradrenergic neurons of the
      locus ceruleus recorded in vitro.
AB  - The neuropeptide corticotropin-releasing hormone (CRH) activates locus ceruleus
      (LC) neurons, thereby increasing norepinephrine levels throughout the CNS.
      Despite anatomical and physiological evidence for CRH innervation of the LC, the
      mechanism of CRH-evoked activation of LC neurons is unknown. Moreover, given the
      apparent absence of mRNA for CRH receptors in LC neurons, the exact location of
      action of CRH within the cerulear region is debated. Using in vitro intracellular
      recordings from rat brainstem, we examined whether CRH exerts a direct effect on
      LC neurons and which ionic currents are likely affected by CRH. We demonstrate
      that CRH dose-dependently increases the firing rate of LC neurons through a
      direct (TTX- and cadmium-insensitive) mechanism by decreasing a potassium
      conductance. The CRH-evoked activation of LC neurons is, at least in part,
      mediated by CRH1 receptors and a cAMP-dependent second messenger system. These
      data provide additional support that CRH functions as an excitatory
      neurotransmitter in the LC and the hypothesis that dysfunction of the CRH
      peptidergic and noradrenergic systems observed in patients with mood and anxiety
      disorders are functionally related.

PMID- 15509760
TI  - Temporally specific burst in cell proliferation increases hippocampal
      neurogenesis in protracted abstinence from alcohol.
AB  - Adult neurogenesis is a newly considered form of plasticity that could contribute
      to brain dysfunction in psychiatric disease. Chronic alcoholism, a disease
      affecting over 8% of the adult population, produces cognitive impairments and
      decreased brain volumes, both of which are partially reversed during abstinence.
      Clinical data and animal models implicate the hippocampus, a region important in
      learning and memory. In a model of alcohol dependence (chronic binge exposure for
      4 d), we show that adult neurogenesis is inhibited during dependence with a
      pronounced increase in new hippocampal neuron formation after weeks of
      abstinence. This increase is attributable to a temporally and regionally specific
      fourfold increase in cell proliferation at day 7 of abstinence, with a majority
      of those cells surviving and differentiating at percentages similar to controls,
      effects that doubled the formation of new neurons. Although increases in cell
      proliferation correlated with alcohol withdrawal severity, proliferation remained
      increased when diazepam (10 mg/kg) was used to reduce withdrawal severity.
      Indeed, those animals with little withdrawal activity still show a twofold burst
      in cell proliferation at day 7 of abstinence. Thus, alcohol dependence and
      recovery from dependence continues to alter hippocampal plasticity during
      abstinence. Because neurogenesis may contribute to hippocampal function and/or
      learning, memory, and mood, compensatory neurogenesis and the return of normal
      neurogenesis may also have an impact on hippocampal structure and function. For
      the first time, these data provide a neurobiological mechanism that may underlie
      the return of human cognitive function and brain volume associated with recovery
      from addiction.

PMID- 15509761
TI  - Intrinsic noise in cultured hippocampal neurons: experiment and modeling.
AB  - Ion channels open and close stochastically. The fluctuation of these channels
      represents an intrinsic source of noise that affects the input-output properties
      of the neuron. We combined whole-cell measurements with biophysical modeling to
      characterize the intrinsic stochastic and electrical properties of single neurons
      as observed at the soma. We measured current and voltage noise in 18 d
      postembryonic cultured neurons from the rat hippocampus, at various subthreshold
      and near-threshold holding potentials in the presence of synaptic blockers. The
      observed current noise increased with depolarization, as ion channels were
      activated, and its spectrum demonstrated generalized 1/f behavior. Exposure to
      TTX removed a significant contribution from Na+ channels to the noise spectrum,
      particularly at depolarized potentials, and the resulting spectrum was now
      dominated by a single Lorentzian (1/f2) component. By replacing the intracellular
      K+ with Cs+, we demonstrated that a major portion of the observed noise was
      attributable to K+ channels. We compared the measured power spectral densities to
      a 1-D cable model of channel fluctuations based on Markov kinetics. We found that
      a somatic compartment, in combination with a single equivalent cylinder,
      described the effective geometry from the viewpoint of the soma. Four distinct
      channel populations were distributed in the membrane and modeled as Lorentzian
      current noise sources. Using the NEURON simulation program, we summed up the
      contributions from the spatially distributed current noise sources and calculated
      the total voltage and current noise. Our quantitative model reproduces important
      voltage- and frequency-dependent features of the data, accounting for the 1/f
      behavior, as well as the effects of various blockers.

PMID- 15509762
TI  - Regulation of brain proteolytic activity is necessary for the in vivo function of
      NMDA receptors.
AB  - Serine proteases are considered to be involved in plasticity-related events in
      the nervous system, but their in vivo targets and the importance of their control
      by endogenous inhibitors are still not clarified. Here, we demonstrate the
      crucial role of a potent serine protease inhibitor, protease nexin-1 (PN-1), in
      the regulation of activity-dependent brain proteolytic activity and the
      functioning of sensory pathways. Neuronal activity regulates the expression of PN
      1, which in turn controls brain proteolytic activity. In PN-1-/- mice, absence of
      PN-1 leads to increased brain proteolytic activity, which is correlated with an
      activity-dependent decrease in the NR1 subunit of the NMDA receptor.
      Correspondingly, reduced NMDA receptor signaling is detected in their barrel
      cortex. This is coupled to decreased sensory evoked potentials in the barrel
      cortex and impaired whisker-dependent sensory motor function. Thus, a tight
      control of serine protease activity is critical for the in vivo function of the
      NMDA receptors and the proper function of sensory pathways.

PMID- 15509763
TI  - Human embryonic stem cells: prospects for development.
AB  - It is widely anticipated that human embryonic stem (ES) cells will serve as an
      experimental model for studying early development in our species, and,
      conversely, that studies of development in model systems, the mouse in
      particular, will inform our efforts to manipulate human stem cells in vitro. A
      comparison of primate and mouse ES cells suggests that a common underlying
      blueprint for the pluripotent state has undergone significant species-specific
      modification. As we discuss here, technical advances in the propagation and
      manipulation of human ES cells have improved our understanding of their growth
      and differentiation, providing the potential to investigate early human
      development and to develop new clinical therapies.

PMID- 15509764
TI  - Embryonic signaling centers expressing BMP, WNT and FGF proteins interact to
      pattern the cerebral cortex.
AB  - Recent findings implicate embryonic signaling centers in patterning the mammalian
      cerebral cortex. We used mouse in utero electroporation and mutant analysis to
      test whether cortical signaling sources interact to regulate one another. We
      identified interactions between the cortical hem, rich in Wingless-Int (WNT)
      proteins and bone morphogenetic proteins (BMPs), and an anterior telencephalic
      source of fibroblast growth factors (FGFs). Expanding the FGF8 domain suppressed
      Wnt2b, Wnt3a and Wnt5a expression in the hem. Next to the hem, the hippocampus
      was shrunken, consistent with its dependence for growth on a hem-derived WNT
      signal. Maintenance of hem WNT signaling and hippocampal development thus require
      a constraint on the FGF8 source, which is likely to be supplied by BMP activity.
      When endogenous BMP signaling is inhibited by noggin, robust Fgf8 expression
      appears ectopically in the cortical primordium. Abnormal signaling centers were
      further investigated in mice lacking the transcription factor EMX2, in which FGF8
      activity is increased, WNT expression reduced, and the hippocampus defective.
      Suggesting that these defects are causally related, sequestering FGF8 in Emx2
      homozygous mutants substantially recovered WNT expression in the hem and
      partially rescued hippocampal development. Because noggin can induce Fgf8
      expression, we examined noggin and BMP signaling in the Emx2 mutant. As the
      telencephalic vesicle closed, Nog expression was expanded and BMP activity
      reduced, potentially leading to FGF8 upregulation. Our findings point to a cross
      regulation of BMP, FGF, and WNT signaling in the early telencephalon, integrated
      by EMX2, and required for normal cortical development.

PMID- 15509765
TI  - The gene FLORAL ORGAN NUMBER1 regulates floral meristem size in rice and encodes
      a leucine-rich repeat receptor kinase orthologous to Arabidopsis CLAVATA1.
AB  - The regulation of floral organ number is closely associated with floral meristem
      size. Mutations in the gene FLORAL ORGAN NUMBER1 (FON1) cause enlargement of the
      floral meristem in Oryza sativa (rice), resulting in an increase in the number of
      all floral organs. Ectopic floral organs develop in the whorl of each organ
      and/or in the additional whorls that form. Inner floral organs are more severely
      affected than outer floral organs. Many carpel primordia develop indeterminately,
      and undifferentiated meristematic tissues remain in the center in almost-mature
      flowers. Consistent with this result, OSH1, a molecular marker of meristematic
      indeterminate cells in rice, continues to be expressed in this region. Although
      floral meristems are strongly affected by the fon1-2 mutation, vegetative and
      inflorescence meristems are largely normal, even in this strong allele. We
      isolated the FON1 gene by positional cloning and found that it encodes a leucine
      rich repeat receptor-like kinase most similar to CLAVATA1 (CLV1) in Arabidopsis
      thaliana. This suggests that a pathway similar to the CLV signaling system that
      regulates meristem maintenance in Arabidopsis is conserved in the grass family.
      Unlike CLV1, which is predominantly expressed in the L3 layer of the shoot
      meristem, FON1 is expressed throughout the whole floral meristem, suggesting that
      small modifications to the CLV signaling pathway may be required to maintain the
      floral meristem in rice. In addition, FON1 transcripts are detected in all
      meristems responsible for development of the aerial part of rice, suggesting that
      genes sharing functional redundancy with FON1 act in the vegetative and
      inflorescence meristems to mask the effects of the fon1 mutation.

PMID- 15509766
TI  - Delta proteins and MAGI proteins: an interaction of Notch ligands with
      intracellular scaffolding molecules and its significance for zebrafish
      development.
AB  - Delta proteins activate Notch through a binding reaction that depends on their
      extracellular domains; but the intracellular (C-terminal) domains of the Deltas
      also have significant functions. All classes of vertebrates possess a subset of
      Delta proteins with a conserved ATEV* motif at their C termini. These ATEV Deltas
      include Delta1 and Delta4 in mammals and DeltaD and DeltaC in the zebrafish. We
      show that these Deltas associate with the membrane-associated scaffolding
      proteins MAGI1, MAGI2 and MAGI3, through a direct interaction between the C
      termini of the Deltas and a specific PDZ domain (PDZ4) of the MAGIs. In cultured
      cells and in subsets of cells in the intact zebrafish embryo, DeltaD and MAGI1
      are co-localized at the plasma membrane. The interaction and the co-localization
      can be abolished by injection of a morpholino that blocks the mRNA splicing
      reaction that gives DeltaD its terminal valine, on which the interaction depends.
      Embryos treated in this way appear normal with respect to some known functions of
      DeltaD as a Notch ligand, including the control of somite segmentation,
      neurogenesis, and hypochord formation. They do, however, show an anomalous
      distribution of Rohon-Beard neurons in the dorsal neural tube, suggesting that
      the Delta-MAGI interaction may play some part in the control of neuron migration.

PMID- 15509767
TI  - Neural induction requires BMP inhibition only as a late step, and involves
      signals other than FGF and Wnt antagonists.
AB  - A dominant molecular explanation for neural induction is the 'default model',
      which proposes that the ectoderm is pre-programmed towards a neural fate, but is
      normally inhibited by endogenous BMPs. Although there is strong evidence
      favouring this in Xenopus, data from other organisms suggest more complexity,
      including an involvement of FGF and modulation of Wnt. However, it is generally
      believed that these additional signals also act by inhibiting BMPs. We have
      investigated whether BMP inhibition is necessary and/or sufficient for neural
      induction. In the chick, misexpression of BMP4 in the prospective neural plate
      inhibits the expression of definitive neural markers (Sox2 and late Sox3), but
      does not affect the early expression of Sox3, suggesting that BMP inhibition is
      required only as a late step during neural induction. Inhibition of BMP
      signalling by the potent antagonist Smad6, either alone or together with a
      dominant-negative BMP receptor, Chordin and/or Noggin in competent epiblast is
      not sufficient to induce expression of Sox2 directly, even in combination with
      FGF2, FGF3, FGF4 or FGF8 and/or antagonists of Wnt signalling. These results
      strongly suggest that BMP inhibition is not sufficient for neural induction in
      the chick embryo. To test this in Xenopus, Smad6 mRNA was injected into the A4
      blastomere (which reliably contributes to epidermis but not to neural plate or
      its border) at the 32-cell stage: expression of neural markers (Sox3 and NCAM) is
      not induced. We propose that neural induction involves additional signalling
      events that remain to be identified.

PMID- 15509768
TI  - Differing strategies for the establishment and maintenance of teashirt and
      homothorax repression in the Drosophila wing.
AB  - Secreted signaling molecules such as Wingless (Wg) and Decapentaplegic (Dpp)
      organize positional information along the proximodistal (PD) axis of the
      Drosophila wing imaginal disc. Responding cells activate different downstream
      targets depending on the combination and level of these signals and other factors
      present at the time of signal transduction. Two such factors, teashirt (tsh) and
      homothorax (hth), are initially co-expressed throughout the entire wing disc, but
      are later repressed in distal cells, permitting the subsequent elaboration of
      distal fates. Control of tsh and hth repression is, therefore, crucial for wing
      development, and plays a role in shaping and sizing the adult appendage. Although
      both Wg and Dpp participate in this control, their specific contributions remain
      unclear. In this report, we analyze tsh and hthregulation in the wing disc, and
      show that Wg and Dpp act independently as the primary signals for the repression
      of tsh and hth, respectively. In cells that receive low levels of Dpp, hth
      repression also requires Vestigial (Vg). Furthermore, although Dpp is required
      continuously for hth repression throughout development, Wg is only required for
      the initiation of tsh repression. Instead, the maintenance of tsh repression
      requires Polycomb group (PcG) mediated gene silencing, which is dispensable for
      hth repression. Thus, despite their overall similar expression patterns, tsh and
      hth repression in the wing disc is controlled by two very different mechanisms.

PMID- 15509770
TI  - An essential role for Fgfs in endodermal pouch formation influences later
      craniofacial skeletal patterning.
AB  - Fibroblast growth factor (Fgf) proteins are important regulators of pharyngeal
      arch development. Analyses of Fgf8 function in chick and mouse and Fgf3 function
      in zebrafish have demonstrated a role for Fgfs in the differentiation and
      survival of postmigratory neural crest cells (NCC) that give rise to the
      pharyngeal skeleton. Here we describe, in zebrafish, an earlier, essential
      function for Fgf8 and Fgf3 in regulating the segmentation of the pharyngeal
      endoderm into pouches. Using time-lapse microscopy, we show that pharyngeal
      pouches form by the directed lateral migration of discrete clusters of endodermal
      cells. In animals doubly reduced for Fgf8 and Fgf3, the migration of pharyngeal
      endodermal cells is disorganized and pouches fail to form. Transplantation and
      pharmacological experiments show that Fgf8 and Fgf3 are required in the neural
      keel and cranial mesoderm during early somite stages to promote first pouch
      formation. In addition, we show that animals doubly reduced for Fgf8 and Fgf3
      have severe reductions in hyoid cartilages and the more posterior branchial
      cartilages. By examining early pouch and later cartilage phenotypes in individual
      animals hypomorphic for Fgf function, we find that alterations in pouch structure
      correlate with later cartilage defects. We present a model in which Fgf signaling
      in the mesoderm and segmented hindbrain organizes the segmentation of the
      pharyngeal endoderm into pouches. Moreover, we argue that the Fgf-dependent
      morphogenesis of the pharyngeal endoderm into pouches is critical for the later
      patterning of pharyngeal cartilages.

PMID- 15509769
TI  - Spalt transcription factors are required for R3/R4 specification and
      establishment of planar cell polarity in the Drosophila eye.
AB  - The establishment of planar cell polarity in the Drosophila eye requires correct
      specification of the R3/R4 pair of photoreceptor cells. In response to a
      polarizing factor, Frizzled signaling specifies R3 and induces Delta, which
      activates Notch in the neighboring cell, specifying it as R4. Here, we show that
      the spalt zinc-finger transcription factors (spalt major and spalt-related) are
      part of the molecular mechanisms regulating R3/R4 specification and planar cell
      polarity establishment. In mosaic analysis, we find that the spalt genes are
      specifically required in R3 for the establishment of correct ommatidial polarity.
      In addition, we show that spalt genes are required for proper localization of
      Flamingo in the equatorial side of R3 and R4, and for the upregulation of Delta
      in R3. These requirements are very similar to those of frizzled during R3/R4
      specification. We show that spalt genes are required cell-autonomously for the
      expression of seven-up in R3 and R4, and that seven-up is downstream of spalt
      genes in the genetic hierarchy of R3/R4 specification. Thus, spalt and seven-up
      are necessary for the correct interpretation of the Frizzled-mediated polarity
      signal in R3. Finally, we show that, posterior to row seven, seven-up represses
      spalt in R3/R4 in order to maintain the R3/R4 identity and to inhibit the
      transformation of these cells to the R7 cell fate.

PMID- 15509771
TI  - The AP1 transcription factor Fra2 is required for efficient cartilage
      development.
AB  - The Fos-related AP1 transcription factor Fra2 (encoded by Fosl2) is expressed in
      various epithelial cells as well as in cartilaginous structures. We studied the
      role of Fra2 in cartilage development. The absence of Fra2 in embryos and
      newborns leads to reduced zones of hypertrophic chondrocytes and impaired matrix
      deposition in femoral and tibial growth plates, probably owing to impaired
      differentiation into hypertrophic chondrocytes. In addition, hypertrophic
      differentiation and ossification of primordial arches of the developing vertebrae
      are delayed in Fra2-deficient embryos. Primary Fosl2-/- chondrocytes exhibit
      decreased hypertrophic differentiation and remain in a proliferative state longer
      than wild-type cells. As pups lacking Fra2 die shortly after birth, we generated
      mice carrying 'floxed' Fosl2 alleles and crossed them to coll2a1-Cre mice,
      allowing investigation of postnatal cartilage development. The coll2a1-Cre,
      Fosl2f/f mice die between 10 and 25 days after birth, are growth retarded and
      display smaller growth plates similar to Fosl2-/- embryos. In addition, these
      mice suffer from a kyphosis-like phenotype, an abnormal bending of the spine.
      Hence, Fra2 is a novel transcription factor important for skeletogenesis by
      affecting chondrocyte differentiation.

PMID- 15509772
TI  - Foxd1 is required for proper formation of the optic chiasm.
AB  - In animals with binocular vision, retinal ganglion cell (RGC) axons from each eye
      sort in the developing ventral diencephalon to project to ipsi- or contralateral
      targets, thereby forming the optic chiasm. Ipsilaterally projecting axons arise
      from the ventrotemporal (VT) retina and contralaterally projecting axons
      primarily from the other retinal quadrants. The winged helix transcription factor
      Foxd1 (previously known as BF-2, Brain Factor 2) is expressed in VT retina, as
      well as in the ventral diencephalon during the formation of the optic chiasm. We
      report here that in embryos lacking Foxd1, both retinal development and chiasm
      morphogenesis are disrupted. In the Foxd1 deficient retina, proteins designating
      the ipsilateral projection, such as Zic2 and EphB1, are missing, and the domain
      of Foxg1 (BF-1) expands from nasal retina into the VT crescent. In retina-chiasm
      co-cultures, VT RGCs from Foxd1 deficient retina are not repulsed by chiasm
      cells, and in vivo many VT RGCs aberrantly project contralaterally. However, even
      though the ipsilateral program is lost in the retina, a larger than normal
      uncrossed component develops in Foxd1 deficient embryos. Chiasm defects include
      axon stalling in the chiasm and a reduction in the total number of RGCs
      projecting to the optic tract. In addition, in the Foxd1 deficient ventral
      diencephalon, Foxg1 invades the Foxd1 domain, Zic2 and Islet1 expression are
      minimized, and Slit2 prematurely expands, changes that could contribute to axon
      projection errors. Thus, Foxd1 plays a dual role in the establishment of the
      binocular visual pathways: first, in specification of the VT retina, acting
      upstream of proteins directing the ipsilateral pathway; and second, in the
      patterning of the developing ventral diencephalon where the optic chiasm forms.

PMID- 15509773
TI  - NCR-1 and NCR-2, the C. elegans homologs of the human Niemann-Pick type C1
      disease protein, function upstream of DAF-9 in the dauer formation pathways.
AB  - Mutations in the human NPC1 gene cause most cases of Niemann-Pick type C (NP-C)
      disease, a fatal autosomal recessive neurodegenerative disorder. NPC1 is
      implicated in intracellular trafficking of cholesterol and glycolipids, but its
      exact function remains unclear. The C. elegans genome contains two homologs of
      NPC1, ncr-1 and ncr-2, and an ncr-2; ncr-1 double deletion mutant forms dauer
      larvae constitutively (Daf-c). We have analyzed the phenotypes of ncr single and
      double mutants in detail, and determined the ncr gene expression patterns. We
      find that the ncr genes function in a hormonal branch of the dauer formation
      pathway upstream of daf-9 and daf-12, which encode a cytochrome P450 enzyme and a
      nuclear hormone receptor, respectively. ncr-1 is expressed broadly in tissues
      with high levels of cholesterol, whereas expression of ncr-2 is restricted to a
      few cells. Both Ncr genes are expressed in the XXX cells, which are implicated in
      regulating dauer formation via the daf-9 pathway. Only the ncr-1 mutant is
      hypersensitive to cholesterol deprivation and to progesterone, an inhibitor of
      intracellular cholesterol trafficking. Our results support the hypothesis that
      ncr-1 and ncr-2 are involved in intracellular cholesterol processing in C.
      elegans, and that a sterol-signaling defect is responsible for the Daf-c
      phenotype of the ncr-2; ncr-1 mutant.

PMID- 15509774
TI  - Inhibition of Jagged-mediated Notch signaling disrupts zebrafish biliary
      development and generates multi-organ defects compatible with an Alagille
      syndrome phenocopy.
AB  - The Alagille Syndrome (AGS) is a heritable disorder affecting the liver and other
      organs. Causative dominant mutations in human Jagged 1 have been identified in
      most AGS patients. Related organ defects occur in mice that carry jagged 1 and
      notch 2 mutations. Multiple jagged and notch genes are expressed in the
      developing zebrafish liver. Compound jagged and notch gene knockdowns alter
      zebrafish biliary, kidney, pancreatic, cardiac and craniofacial development in a
      manner compatible with an AGS phenocopy. These data confirm an evolutionarily
      conserved role for Notch signaling in vertebrate liver development, and support
      the zebrafish as a model system for diseases of the human biliary system.

PMID- 15509775
TI  - Proteasome inhibitor PS-341 induces apoptosis through induction of endoplasmic
      reticulum stress-reactive oxygen species in head and neck squamous cell carcinoma
      cells.
AB  - PS-341, also known as Velcade or Bortezomib, represents a new class of anticancer
      drugs which has been shown to potently inhibit the growth and/or progression of
      human cancers, including head and neck squamous cell carcinoma (HNSCC). Although
      it has been logically hypothesized that NF-kappaB is a major target of PS-341,
      the underlying mechanism by which PS-341 inhibits tumor cell growth is unclear.
      Here we found that PS-341 potently activated the caspase cascade and induced
      apoptosis in human HNSCC cell lines. Although PS-341 could inhibit NF-kappaB
      activation, the inhibition of NF-kappaB was not sufficient to initiate apoptosis
      in HNSCC cells. Using biochemical and microarray approaches, we found that
      proteasome inhibition by PS-341 induced endoplasmic reticulum (ER) stress and
      reactive oxygen species (ROS) in HNSCC cells. The inhibition of ROS significantly
      suppressed caspase activation and apoptosis induced by PS-341. Consistently, PS
      341 could not induce the ER stress-ROS in PS-341-resistant HNSCC cells. Taken
      together, our results suggest that in addition to the abolishment of the
      prosurvival NF-kappaB, PS-341 might directly induce apoptosis by activating
      proapoptotic ER stress-ROS signaling cascades in HNSCC cells, providing novel
      insights into the PS-341-mediated antitumor activity.

PMID- 15509777
TI  - Involvement of insulin receptor substrate 2 in mammary tumor metastasis.
AB  - The insulin receptor substrate (IRS) proteins are adaptor molecules that
      integrate signals generated by receptors that are implicated in human breast
      cancer. We investigated the specific contribution of IRS-2 to mammary tumor
      progression using transgenic mice that express the polyoma virus middle T antigen
      (PyV-MT) in the mammary gland and IRS-2-null (IRS-2(-/-)) mice. PyV-MT-induced
      tumor initiation and growth were similar in wild-type (WT) and IRS-2(-/-) mice.
      However, the latency and incidence of metastasis were significantly decreased in
      the absence of IRS-2 expression. The contribution of IRS-2 to metastasis is
      intrinsic to the tumor cells, because IRS-2(-/-) mammary tumor cells did not
      metastasize when grown orthotopically in the mammary fat pads of WT mice. WT and
      IRS-2(-/-) tumors contained similar numbers of mitotic cells, but IRS-2(-/-)
      tumors had a higher incidence of apoptosis than did WT tumors. In vitro, IRS-2(-/
      ) mammary tumor cells were less invasive and more apoptotic in response to growth
      factor deprivation than their WT counterparts. In contrast, IRS-1(-/-) tumor
      cells, which express only IRS-2, were highly invasive and were resistant to
      apoptotic stimuli. Collectively, our findings reveal an important contribution of
      IRS-2 to breast cancer metastasis.

PMID- 15509776
TI  - Retinoid X receptor regulates Nur77/TR3-dependent apoptosis [corrected] by
      modulating its nuclear export and mitochondrial targeting.
AB  - Retinoid X receptor (RXR) plays a central role in the regulation of intracellular
      receptor signaling pathways by acting as a ubiquitous heterodimerization partner
      of many nuclear receptors, including the orphan receptor Nur77 (also known as TR3
      [corrected] or NGFI-B), which translocates from the nucleus to mitochondria,
      where it interacts with Bcl-2 to induce apoptosis. Here, we report that RXRalpha
      is required for nuclear export and mitochondrial targeting of Nur77 through their
      unique heterodimerization that is mediated by dimerization interfaces located in
      their DNA-binding domain. The effects of RXRalpha are attributed to a putative
      nuclear export sequence (NES) present in its carboxyl-terminal region. RXRalpha
      ligands suppress NES activity by inducing RXRalpha homodimerization or altering
      RXRalpha/Nur77 heterodimerization. The RXRalpha NES is also silenced by RXRalpha
      heterodimerization with retinoic acid receptor or vitamin D receptor.
      Consistently, we were able to show that the mitochondrial targeting of the
      RXRalpha/Nur77 heterodimer and its induction of apoptosis are potently inhibited
      by RXR ligands. Together, our results reveal a novel nongenotropic function of
      RXRalpha and its involvement in the regulation of the Nur77-dependent apoptotic
      pathway [corrected]

PMID- 15509778
TI  - Neonatal lethality of LGR5 null mice is associated with ankyloglossia and
      gastrointestinal distension.
AB  - The physiological role of an orphan G protein-coupled receptor, LGR5, was
      investigated by targeted deletion of this seven-transmembrane protein containing
      a large N-terminal extracellular domain with leucine-rich repeats. LGR5 null mice
      exhibited 100% neonatal lethality characterized by gastrointestinal tract
      dilation with air and an absence of milk in the stomach. Gross and histological
      examination revealed fusion of the tongue to the floor of oral cavity in the
      mutant newborns and immunostaining of LGR5 expression in the epithelium of the
      tongue and in the mandible of the wild-type embryos. The observed ankyloglossia
      phenotype provides a model for understanding the genetic basis of this
      craniofacial defect in humans and an opportunity to elucidate the physiological
      role of the LGR5 signaling system during embryonic development.

PMID- 15509779
TI  - Essential requirement of CCAAT/enhancer binding proteins in embryogenesis.
AB  - The CCAAT/enhancer binding proteins C/EBPalpha and C/EBPbeta are related
      transcription factors that are important for the function of various organs in
      the postnatal mouse. Gene replacement and tissue culture experiments have
      suggested partial redundancy of both transcription factors. Here we show that
      mouse embryos deficient of both C/EBPalpha and C/EBPbeta (C/EBPalphabeta(-/-))
      die between embryonic day 10 (E10) and E11 and display defective placentas. In
      situ hybridization revealed that C/EBPalpha and C/EBPbeta are coexpressed in the
      chorionic plate at E9.5 and later in the trophoblasts of the labyrinthine layer.
      In C/EBPalphabeta(-/-) placentas, allantoic blood vessels invaded the chorion;
      however, vessel expansion and development of the labyrinthine layer was impaired.
      Furthermore, a single copy of either C/EBPalpha in the absence of C/EBPbeta or
      C/EBPbeta in the absence of C/EBPalpha is sufficient to complete development,
      suggesting complementation of these C/EBPs during embryogenesis. A single copy of
      C/EBPalpha in the absence of C/EBPbeta, however, fails to rescue survival after
      birth, suggesting haploinsufficiency of C/EBPalpha in newborns. Our data thus
      reveal novel essential, redundant, and dosage dependent functions of C/EBPs.

PMID- 15509781
TI  - Calcium binding of ARC mediates regulation of caspase 8 and cell death.
AB  - Apoptosis repressor with CARD (ARC) possesses the ability not only to block
      activation of caspase 8 but to modulate caspase-independent mitochondrial events
      associated with cell death. However, it is not known how ARC modulates both
      caspase-dependent and caspase-independent cell death. Here, we report that ARC is
      a Ca(2+)-dependent regulator of caspase 8 and cell death. We found that in Ca(2+)
      overlay and Stains-all assays, ARC protein bound to Ca(2+) through the C-terminal
      proline/glutamate-rich (P/E-rich) domain. ARC expression reduced not only
      cytosolic Ca(2+) transients but also cytotoxic effects of thapsigargin, A23187,
      and ionomycin, for which the Ca(2+)-binding domain of ARC was indispensable.
      Conversely, direct interference of endogenous ARC synthesis by targeting ARC
      enhanced such Ca(2+)-mediated cell death. In addition, binding and
      immunoprecipitation analyses revealed that the protein-protein interaction
      between ARC and caspase 8 was decreased by the increase of Ca(2+) concentration
      in vitro and by the treatment of HEK293 cells with thapsigargin in vivo. Caspase
      8 activation was also required for the thapsigargin-induced cell death and
      suppressed by the ectopic expression of ARC. These results suggest that calcium
      binding mediates regulation of caspase 8 and cell death by ARC.

PMID- 15509780
TI  - The TBC (Tre-2/Bub2/Cdc16) domain protein TRE17 regulates plasma membrane
      endosomal trafficking through activation of Arf6.
AB  - TBC (Tre-2/Bub2/Cdc16) domains are predicted to encode GTPase-activating proteins
      (GAPs) for Rab family G proteins. While approximately 50 TBC proteins are
      predicted to exist in humans, little is known about their substrate specificity.
      Here we show that TRE17 (also called Tre-2 and USP6), a founding member of the
      TBC family, targets the Arf family GTPase Arf6, which regulates plasma membrane
      endosome trafficking. Surprisingly, TRE17 does not function as a GAP for Arf6 but
      rather promotes its activation in vivo. TRE17 associates directly with Arf6 in
      its GDP- but not GTP-bound state. Mapping experiments pinpoint the site of
      interaction to the TBC domain of TRE17. Forced expression of TRE17 promotes the
      localization of Arf6 to the plasma membrane, leading to Arf6 activation,
      presumably due to facilitated access to membrane-associated guanine nucleotide
      exchange factors (GEFs). Furthermore, TRE17 cooperates with Arf6 GEFs to induce
      GTP loading of Arf6 in vivo. Finally, short interfering RNA-mediated loss of
      TRE17 leads to attenuated Arf6 activation. These studies identify TRE17 as a
      novel regulator of the Arf6-regulated plasma membrane recycling system and reveal
      an unexpected function for TBC domains.

PMID- 15509782
TI  - Amino acid signaling in yeast: casein kinase I and the Ssy5 endoprotease are key
      determinants of endoproteolytic activation of the membrane-bound Stp1
      transcription factor.
AB  - Saccharomyces cerevisiae cells possess a plasma membrane sensor able to detect
      the presence of extracellular amino acids and then to activate a signaling
      pathway leading to transcriptional induction of multiple genes, e.g., AGP1,
      encoding an amino acid permease. This sensing function requires the permease-like
      Ssy1 and associated Ptr3 and Ssy5 proteins, all essential to activation, by
      endoproteolytic processing, of the membrane-bound Stp1 transcription factor. The
      SCF(Grr1) ubiquitin-ligase complex is also essential to AGP1 induction, but its
      exact role in the amino acid signaling pathway remains unclear. Here we show that
      Stp1 undergoes casein kinase I-dependent phosphorylation. In the yck mutant
      lacking this kinase, Stp1 is not cleaved and AGP1 is not induced in response to
      amino acids. Furthermore, we provide evidence that Ssy5 is the endoprotease
      responsible for Stp1 processing. Ssy5 is significantly similar to serine
      proteases, its self-processing is a prerequisite for Stp1 cleavage, and its
      overexpression causes inducer-independent Stp1 cleavage and high-level AGP1
      transcription. We further show that Stp1 processing also requires the SCF(Grr1)
      complex but is insensitive to proteasome inhibition. However, Stp1 processing
      does not require SCF(Grr1), Ssy1, or Ptr3 when Ssy5 is overproduced. Finally, we
      describe the properties of a particular ptr3 mutant that suggest that Ptr3 acts
      with Ssy1 in amino acid detection and signal initiation. We propose that Ssy1 and
      Ptr3 form the core components of the amino acid sensor. Upon detection of
      external amino acids, Ssy1-Ptr3 likely allows-in a manner dependent on SCF(Grr1)
      the Ssy5 endoprotease to gain access to and to cleave Stp1, this requiring prior
      phosphorylation of Stp1 by casein kinase I.

PMID- 15509783
TI  - Kinetochore targeting of fission yeast Mad and Bub proteins is essential for
      spindle checkpoint function but not for all chromosome segregation roles of
      Bub1p.
AB  - Several lines of evidence suggest that kinetochores are organizing centers for
      the spindle checkpoint response and the synthesis of a "wait anaphase" signal in
      cases of incomplete or improper kinetochore-microtubule attachment. Here we
      characterize Schizosaccharomyces pombe Bub3p and study the recruitment of spindle
      checkpoint components to kinetochores. We demonstrate by chromatin
      immunoprecipitation that they all interact with the central domain of
      centromeres, consistent with their role in monitoring kinetochore-microtubule
      interactions. Bub1p and Bub3p are dependent upon one another, but independent of
      the Mad proteins, for their kinetochore localization. We demonstrate a clear role
      for the highly conserved N-terminal domain of Bub1p in the robust targeting of
      Bub1p, Bub3p, and Mad3p to kinetochores and show that this is crucial for an
      efficient checkpoint response. Surprisingly, neither this domain nor kinetochore
      localization is required for other functions of Bub1p in chromosome segregation.

PMID- 15509784
TI  - Tankyrase polymerization is controlled by its sterile alpha motif and poly(ADP
      ribose) polymerase domains.
AB  - Tankyrases are novel poly(ADP-ribose) polymerases that have SAM and ankyrin
      protein-interaction domains. They are found at telomeres, centrosomes, nuclear
      pores, and Golgi vesicles and have been shown to participate in telomere length
      regulation. Their other function(s) are unknown, and it has been difficult to
      envision a common role at such diverse cellular locations. We have shown that
      tankyrase 1 polymerizes through its sterile alpha motif (SAM) domain to assemble
      large protein complexes. In vitro polymerization is reversible and still allows
      interaction with ankyrin-domain binding proteins. Polymerization can also occur
      in vivo, with SAM-dependent association of overexpressed tankyrase leading to
      formation of large tankyrase-containing vesicles, disruption of Golgi structure,
      and inhibition of apical secretion. Finally, tankyrase polymers are dissociated
      efficiently by poly(ADP-ribosy)lation. This disassembly is prevented by mutation
      of the PARP domain. Our findings indicate that tankyrase 1 has the unique
      capacity to promote both assembly and disassembly of large protein complexes.
      Thus, tankyrases appear to be master scaffolding proteins that regulate the
      formation of dynamic protein networks at different cellular locations. This
      implies a common scaffolding function for tankyrases at each location, with
      specific tankyrase interaction partners conferring location-specific roles to
      each network, e.g., telomere compaction or regulation of vesicle trafficking.

PMID- 15509785
TI  - Biochemical interactions between proteins and mat1 cis-acting sequences required
      for imprinting in fission yeast.
AB  - DNA recombination required for mating type (mat1) switching in
      Schizosaccharomyces pombe is initiated by mat1 imprinting. The imprinting event
      is regulated by mat1 cis-acting elements and by several trans-acting factors,
      including swi1 (for switch), swi3, swi7, and sap1. swi1 and swi3 were previously
      shown to function in dictating unidirectional mat1 DNA replication by controlling
      replication fork movement around the mat1 region and, second, by pausing fork
      progression around the imprint site. With biochemical studies, we investigated
      whether the trans-acting factors function indirectly or directly by binding to
      the mat1 cis-acting sequences. First, we report the identification and DNA
      sequence of the swi3 gene. swi3 is not essential for viability, and, like the
      other factors, it exerts a stimulatory effect on imprinting. Second, we showed
      that only Swi1p and Swi3p interact to form a multiprotein complex and that
      complex formation did not require their binding to a DNA region defined by the
      smt-0 mutation. Third, we found that the Swi1p-Swi3p complex physically binds to
      a region around the imprint site where pausing of replication occurs. Fourth, the
      protein complex also interacted with the mat1-proximal polar terminator of
      replication (RTS1). These results suggest that the stimulatory effect of swi1 and
      swi3 on switching and imprinting occurs through interaction of the Swi1p-Swi3p
      complex with the mat1 regions.

PMID- 15509786
TI  - Architectural role of mitochondrial transcription factor A in maintenance of
      human mitochondrial DNA.
AB  - Mitochondrial transcription factor A (TFAM), a transcription factor for
      mitochondrial DNA (mtDNA) that also possesses the property of nonspecific DNA
      binding, is essential for maintenance of mtDNA. To clarify the role of TFAM, we
      repressed the expression of endogenous TFAM in HeLa cells by RNA interference.
      The amount of TFAM decreased maximally to about 15% of the normal level at day 3
      after RNA interference and then recovered gradually. The amount of mtDNA changed
      closely in parallel with the daily change in TFAM while in organello
      transcription of mtDNA at day 3 was maintained at about 50% of the normal level.
      TFAM lacking its C-terminal 25 amino acids (TFAM-DeltaC) marginally activated
      transcription in vitro. When TFAM-DeltaC was expressed at levels comparable to
      those of endogenous TFAM in HeLa cells, mtDNA increased twofold, suggesting that
      TFAM-DeltaC is as competent in maintaining mtDNA as endogenous TFAM under these
      conditions. The in organello transcription of TFAM-DeltaC-expressing cells was no
      more than that in the control. Thus, the mtDNA amount is finely correlated with
      the amount of TFAM but not with the transcription level. We discuss an
      architectural role for TFAM in the maintenance of mtDNA in addition to its role
      in transcription activation.

PMID- 15509787
TI  - Differential regulation of Hand1 homodimer and Hand1-E12 heterodimer activity by
      the cofactor FHL2.
AB  - The basic helix-loop-helix (bHLH) factor Hand1 plays an essential role in cardiac
      morphogenesis, and yet its precise function remains unknown. Protein-protein
      interactions involving Hand1 provide a means of determining how Hand1-induced
      gene expression in the developing heart might be regulated. Hand1 is known to
      form either heterodimers with near-ubiquitous E-factors and other lineage
      restricted class B bHLH proteins or homodimers with itself in vitro. To date,
      there have been no reported Hand1 protein interactions involving non-bHLH
      proteins. Heterodimer-versus-homodimer choice is mediated by the phosphorylation
      status of Hand1; however, little is known about the in vivo function of these
      dimers or, importantly, how they are regulated. In an effort to understand how
      Hand1 activity in the heart might be regulated postdimerization, we have
      investigated tertiary Hand1-protein interactions with non-bHLH factors. We
      describe a novel interaction of Hand1 with the LIM domain protein FHL2, a known
      transcriptional coactivator and corepressor expressed in the developing
      cardiovascular system. FHL2 interacts with Hand1 via the bHLH domain and is able
      to repress Hand1/E12 heterodimer-induced transcription but has no effect on
      Hand1/Hand1 homodimer activity. This effect of FHL2 is not mediated either at the
      level of dimerization or via an effect of Hand1/E12 DNA binding. In summary, our
      data describe a novel differential regulation of Hand1 heterodimers versus
      homodimers by association of the cofactor FHL2 and provide insight into the
      potential for a tertiary level of control of Hand1 activity in the developing
      heart.

PMID- 15509788
TI  - Neuroprotective role of the Reaper-related serine protease HtrA2/Omi revealed by
      targeted deletion in mice.
AB  - The serine protease HtrA2/Omi is released from the mitochondrial intermembrane
      space following apoptotic stimuli. Once in the cytosol, HtrA2/Omi has been
      implicated in promoting cell death by binding to inhibitor of apoptosis proteins
      (IAPs) via its amino-terminal Reaper-related motif, thus inducing caspase
      activity, and also in mediating caspase-independent death through its own
      protease activity. We report here the phenotype of mice entirely lacking
      expression of HtrA2/Omi due to targeted deletion of its gene, Prss25. These
      animals, or cells derived from them, show no evidence of reduced rates of cell
      death but on the contrary suffer loss of a population of neurons in the striatum,
      resulting in a neurodegenerative disorder with a parkinsonian phenotype that
      leads to death of the mice around 30 days after birth. The phenotype of these
      mice suggests that it is the protease function of this protein and not its IAP
      binding motif that is critical. This conclusion is reinforced by the finding that
      simultaneous deletion of the other major IAP binding protein, Smac/DIABLO, does
      not obviously alter the phenotype of HtrA2/Omi knockout mice or cells derived
      from them. Mammalian HtrA2/Omi is therefore likely to function in vivo in a
      manner similar to that of its bacterial homologues DegS and DegP, which are
      involved in protection against cell stress, and not like the proapoptotic Reaper
      family proteins in Drosophila melanogaster.

PMID- 15509789
TI  - ETO/MTG8 is an inhibitor of C/EBPbeta activity and a regulator of early
      adipogenesis.
AB  - The putative transcriptional corepressor ETO/MTG8 has been extensively studied
      due to its involvement in a chromosomal translocation causing the t(8;21) form of
      acute myeloid leukemia. Despite this, the role of ETO in normal physiology has
      remained obscure. Here we show that ETO is highly expressed in preadipocytes and
      acts as an inhibitor of C/EBPbeta during early adipogenesis, contributing to its
      characteristically delayed activation. ETO prevents both the transcriptional
      activation of the C/EBPalpha promoter by C/EBPbeta and its concurrent
      accumulation in centromeric sites during early adipogenesis. ETO expression
      rapidly reduces after the initiation of adipogenesis, and this is essential to
      the normal induction of adipogenic gene expression. These findings define, for
      the first time, a molecular role for ETO in normal physiology as an inhibitor of
      C/EBPbeta and a novel regulator of early adipogenesis.

PMID- 15509790
TI  - Novel functional dissection of the localization-specific roles of budding yeast
      polo kinase Cdc5p.
AB  - Budding yeast polo kinase Cdc5p localizes to the spindle pole body (SPB) and to
      the bud-neck and plays multiple roles during M-phase progression. To dissect
      localization-specific mitotic functions of Cdc5p, we tethered a localization
      defective N-terminal kinase domain of Cdc5p (Cdc5pDeltaC) to the SPB or to the
      bud-neck with components specifically localizing to one of these sites and
      characterized these mutants in a cdc5Delta background. Characterization of a
      viable, SPB-localizing, CDC5DeltaC-CNM67 mutant revealed that it is defective in
      timely degradation of Swe1p, a negative regulator of Cdc28p. Loss of BFA1, a
      negative regulator of mitotic exit, rescued the lethality of a neck-localizing
      CDC5DeltaC-CDC12 or CDC5DeltaC-CDC3 mutant but yielded severe defects in
      cytokinesis. These data suggest that the SPB-associated Cdc5p activity is
      critical for both mitotic exit and cytokinesis, whereas the bud neck-localized
      Cdc5p is required for proper Swe1p regulation. Interestingly, a cdc5Delta
      bfa1Delta swe1Delta triple mutant is viable but grows slowly, whereas cdc5Delta
      cells bearing both CDC5DeltaC-CNM67 and CDC5DeltaC-CDC12 grow well with only a
      mild cell cycle delay. Thus, SPB- and the bud-neck-localized Cdc5p control most
      of the critical Cdc5p functions and downregulation of Bfa1p and Swe1p at the
      respective locations are two critical factors that require Cdc5p.

PMID- 15509791
TI  - Ty1 mobilizes subtelomeric Y' elements in telomerase-negative Saccharomyces
      cerevisiae survivors.
AB  - When telomerase is inactivated in Saccharomyces cerevisiae, telomeric DNA
      shortens with every cell division, and cells stop dividing after approximately
      100 generations. Survivors that form in these senescent populations and resume
      growing have variably amplified arrays of subtelomeric Y' elements. We marked a
      chromosomal Y' element with the his3AI retrotransposition indicator gene and
      found that Y'HIS3 cDNA was incorporated into the genome at approximately 10- to
      1,000-fold-higher frequencies in survivors compared to telomerase-positive
      strains. Y'HIS3 cDNA mobility was significantly reduced if assayed at 30 degrees
      C, a nonpermissive temperature for Ty1 retrotransposition, or in the absence of
      Tec1p, a transcription factor for Ty1. Microarray analysis revealed that Y' RNA
      is preferentially associated with Ty1 virus-like particles (VLPs). Genomic copies
      of Y'HIS3 cDNA typically have downstream oligo(A) tracts, followed by a complete
      Ty1 long terminal repeat and TYA1 or TYB1 sequences. These data are consistent
      with the use of Ty1 cDNA to prime reverse transcription of polyadenylated Y' RNA
      within Ty1 VLPs. Unmarked Y'-oligo(A)-Ty1 cDNA was also detected in survivors,
      reaching copy numbers of approximately 10(-2) per genome. We propose that Y'
      oligo(A)-Ty1 cDNA recombines with Y' elements at eroding telomeres in survivors
      and may play a role in telomere maintenance in the absence of telomerase.

PMID- 15509792
TI  - The Wt1+/R394W mouse displays glomerulosclerosis and early-onset renal failure
      characteristic of human Denys-Drash syndrome.
AB  - Renal failure is a frequent and costly complication of many chronic diseases,
      including diabetes and hypertension. One common feature of renal failure is
      glomerulosclerosis, the pathobiology of which is unclear. To help elucidate this,
      we generated a mouse strain carrying the missense mutation Wt1 R394W, which
      predisposes humans to glomerulosclerosis and early-onset renal failure (Denys
      Drash syndrome [DDS]). Kidney development was normal in Wt1(+/R394W)
      heterozygotes. However, by 4 months of age 100% of male heterozygotes displayed
      proteinuria and glomerulosclerosis characteristic of DDS patients. This phenotype
      was observed in an MF1 background but not in a mixed B6/129 background,
      suggestive of the action of a strain-specific modifying gene(s). WT1 encodes a
      nuclear transcription factor, and the R394W mutation is known to impair this
      function. Therefore, to investigate the mechanism of Wt1 R394W-induced renal
      failure, the expression of genes whose deletion leads to glomerulosclerosis
      (NPHS1, NPHS2, and CD2AP) was quantitated. In mutant kidneys, NPHS1 and NPHS2
      were only moderately downregulated (25 to 30%) at birth but not at 2 or 4 months.
      Expression of CD2AP was not changed at birth but was significantly upregulated at
      2 and 4 months. Podocalyxin was downregulated by 20% in newborn kidneys but not
      in kidneys at later ages. Two other genes implicated in glomerulosclerosis, TGFB1
      and IGF1, were upregulated at 2 months and at 2 and 4 months, respectively. It is
      not clear whether the significant alterations in gene expression are a cause or a
      consequence of the disease process. However, the data do suggest that Wt1 R394W
      induced glomerulosclerosis may be independent of downregulation of the genes for
      NPHS1, NPHS2, CD2AP, and podocalyxin and may involve other genes yet to be
      implicated in renal failure. The Wt1(R394W) mouse recapitulates the pathology and
      disease progression observed in patients carrying the same mutation, and the
      mutation is completely penetrant in male animals. Thus, it will be a powerful and
      biologically relevant model for investigating the pathobiology of the earliest
      events in glomerulosclerosis.

PMID- 15509793
TI  - In vivo requirement of the RNA polymerase II elongation factor elongin A for
      proper gene expression and development.
AB  - A number of transcription factors that increase the catalytic rate of mRNA
      synthesis by RNA polymerase II (Pol II) have been purified from higher
      eukaryotes. Among these are the ELL family, DSIF, and the heterotrimeric elongin
      complex. Elongin A, the largest subunit of the elongin complex, is the
      transcriptionally active subunit, while the smaller elongin B and C subunits
      appear to act as regulatory subunits. While much is known about the in vitro
      properties of elongin A and other members of this class of elongation factors,
      the physiological role(s) of these proteins remain largely unclear. To elucidate
      in vivo functions of elongin A, we have characterized its Drosophila homologue
      (dEloA). dEloA associates with transcriptionally active puff sites within
      Drosophila polytene chromosomes and exhibits many of the expected biochemical and
      cytological properties consistent with a Pol II-associated elongation factor. RNA
      interference-mediated depletion of dEloA demonstrated that elongin A is an
      essential factor that is required for proper metamorphosis. Consistent with this
      observation, dEloA expression peaks during the larval stages of development,
      suggesting that this factor may be important for proper regulation of
      developmental events during these stages. The discovery of the role of elongin A
      in an in vivo model system defines the novel contribution played by RNA
      polymerase II elongation machinery in regulation of gene expression that is
      required for proper development.

PMID- 15509794
TI  - Inactivation of the Mgat1 gene in oocytes impairs oogenesis, but embryos lacking
      complex and hybrid N-glycans develop and implant.
AB  - Complex and hybrid N-glycans contain sugar residues that have been implicated in
      fertilization, compaction of the embryo, and implantation. Inactivation of the
      Mgat1 gene responsible for their synthesis is embryonic lethal, but homozygous
      mutant blastocysts are phenotypically normal due to the presence of maternal
      Mgat1 gene transcripts. To identify roles for complex and hybrid N-glycans in
      oogenesis and preimplantation development, the Mgat1 gene in oocytes was deleted
      by using a ZP3Cre recombinase transgene. All mutant oocytes had an altered zona
      pellucida (ZP) that was thinner than the control ZP, and they did not possess
      complex N-glycans but contained ZP1, ZP2, and ZP3 glycoproteins. Mutant eggs were
      fertilized, all embryos implanted, and heterozygotes developed to birth. However,
      mutant females had decreased fertility, yielded fewer eggs after stimulation with
      gonadotropins, and produced a reduced number of preimplantation embryos and less
      progeny than controls. About 25% of embryonic day 3.5 (E3.5) embryos derived from
      mutant eggs were severely retarded in development, even when they were
      heterozygous and expressed complex N-glycans. Thus, a proportion of Mgat1(-)(/)(
      ) oocytes were developmentally compromised. Surprisingly, mutant eggs also gave
      rise to Mgat1(-)(/)(-) embryos that developed normally, implanted, and progressed
      to E9.5. Therefore, complex or hybrid N-glycans are required at some stage of
      oogenesis for the generation of a developmentally competent oocyte, but
      fertilization, blastogenesis, and implantation may proceed in their absence.

PMID- 15509795
TI  - Inducible gene trapping with drug-selectable markers and Cre/loxP to identify
      developmentally regulated genes.
AB  - Gene trapping in mouse embryonic stem cells is an important genetic approach that
      allows simultaneous mutation of genes and generation of corresponding mutant
      mice. We designed a selection scheme with drug selection markers and Cre/loxP
      technology which allows screening of gene trap events that responded to a
      signaling molecule in a 96-well format. Nine hundred twenty gene trap clones were
      assayed, and 258 were classified as gene traps induced by in vitro
      differentiation. Sixty-five of the in vitro differentiation-inducible gene traps
      were also responsive to retinoic acid treatment. In vivo analysis revealed that
      85% of the retinoic acid-inducible gene traps trapped developmentally regulated
      genes, consistent with the observation that genes induced by retinoic acid
      treatment are likely to be developmentally regulated. Our results demonstrate
      that the inducible gene trapping system described here can be used to enrich in
      vitro for traps in genes of interest. Furthermore, we demonstrate that the cre
      reporter is extremely sensitive and can be used to explore chromosomal regions
      that are not detectable with neo as a selection cassette.

PMID- 15509796
TI  - Carbonic anhydrase III is not required in the mouse for normal growth,
      development, and life span.
AB  - Carbonic anhydrase III is a cytosolic protein which is particularly abundant in
      skeletal muscle, adipocytes, and liver. The specific activity of this isozyme is
      quite low, suggesting that its physiological function is not that of hydrating
      carbon dioxide. To understand the cellular roles of carbonic anhydrase III, we
      inactivated the Car3 gene. Mice lacking carbonic anhydrase III were viable and
      fertile and had normal life spans. Carbonic anhydrase III has also been
      implicated in the response to oxidative stress. We found that mice lacking the
      protein had the same response to a hyperoxic challenge as did their wild-type
      siblings. No anatomic alterations were noted in the mice lacking carbonic
      anhydrase III. They had normal amounts and distribution of fat, despite the fact
      that carbonic anhydrase III constitutes about 30% of the soluble protein in
      adipocytes. We conclude that carbonic anhydrase III is dispensable for mice
      living under standard laboratory husbandry conditions.

PMID- 15509797
TI  - Telomeric DNA in ALT cells is characterized by free telomeric circles and
      heterogeneous t-loops.
AB  - A prerequisite for cellular immortalization in human cells is the elongation of
      telomeres through the upregulation of telomerase or by the alternative
      lengthening of telomeres (ALT) pathway. In this study, telomere structure in
      multiple ALT cell lines was examined by electron microscopy. Nuclei were isolated
      from GM847, GM847-Tert, and WI-38 VA13 ALT cells, psoralen photo-cross-linked in
      situ, and the telomere restriction fragments were purified by gel filtration
      chromatography. Examination of telomere-enriched fractions revealed frequent
      extrachromosomal circles, ranging from 0.7 to 56.8 kb. t-loops were also
      observed, with the loop portion ranging from 0.5 to 70.2 kb. The total length of
      the loop plus tail of the t-loops corresponded to the telomere restriction
      fragment length from the ALT cell lines as determined by pulsed-field gel
      electrophoresis. The presence of extrachromosomal circles containing telomeric
      DNA was confirmed by two-dimensional pulsed-field gel electrophoresis. These
      results show that extrachromosomal telomeric DNA circles are present in ALT
      nuclei and suggest a roll-and-spread mechanism of telomere elongation similar to
      that seen in previous observations of multiple yeast species. Results presented
      here also indicate that expression of telomerase in GM847 cells does not affect t
      loop or extrachromosomal circle formation.

PMID- 15509798
TI  - NAD+ modulates p53 DNA binding specificity and function.
AB  - DNA damage induces p53 DNA binding activity, which affects tumorigenesis, tumor
      responses to therapies, and the toxicities of cancer therapies (B. Vogelstein, D.
      Lane, and A. J. Levine, Nature 408:307-310, 2000; K. H. Vousden and X. Lu, Nat.
      Rev. Cancer 2:594-604, 2002). Both transcriptional and transcription-independent
      activities of p53 contribute to DNA damage-induced cell cycle arrest, apoptosis,
      and aneuploidy prevention (M. B. Kastan et al., Cell 71:587-597, 1992; K. H.
      Vousden and X. Lu, Nat. Rev. Cancer 2:594-604, 2002). Small-molecule manipulation
      of p53 DNA binding activity has been an elusive goal, but here we show that
      NAD(+) binds to p53 tetramers, induces a conformational change, and modulates p53
      DNA binding specificity in vitro. Niacinamide (vitamin B(3)) increases the rate
      of intracellular NAD(+) synthesis, alters radiation-induced p53 DNA binding
      specificity, and modulates activation of a subset of p53 transcriptional targets.
      These effects are likely due to a direct effect of NAD(+) on p53, as a molecule
      structurally related to part of NAD(+), TDP, also inhibits p53 DNA binding, and
      the TDP precursor, thiamine (vitamin B(1)), inhibits intracellular p53 activity.
      Niacinamide and thiamine affect two p53-regulated cellular responses to ionizing
      radiation: rereplication and apoptosis. Thus, niacinamide and thiamine form a
      novel basis for the development of small molecules that affect p53 function in
      vivo, and these results suggest that changes in cellular energy metabolism may
      regulate p53.

PMID- 15509799
TI  - Xenopus Cds1 is regulated by DNA-dependent protein kinase and ATR during the cell
      cycle checkpoint response to double-stranded DNA ends.
AB  - The checkpoint kinase Cds1 (Chk2) plays a key role in cell cycle checkpoint
      responses with functions in cell cycle arrest, DNA repair, and induction of
      apoptosis. Proper regulation of Cds1 is essential for appropriate cellular
      responses to checkpoint-inducing insults. While the kinase ATM has been shown to
      be important in the regulation of human Cds1 (hCds1), here we report that the
      kinases ATR and DNA-dependent protein kinase (DNA-PK) play more significant roles
      in the regulation of Xenopus Cds1 (XCds1). Under normal cell cycle conditions,
      nonactivated XCds1 constitutively associates with a Xenopus ATR complex. The
      association of XCds1 with this complex does not require a functional forkhead
      activation domain but does require a putative SH3 binding region that is found in
      XCds1. In response to double-stranded DNA ends, the amino terminus of XCds1 is
      rapidly phosphorylated in a sequential pattern. First DNA-PK phosphorylates
      serine 39, a site not previously recognized as important in Cds1 regulation.
      Xenopus ATM, ATR, and/or DNA-PK then phosphorylate three consensus
      serine/glutamine sites. Together, these phosphorylations have the dual function
      of inducing dissociation from the ATR complex and independently promoting the
      full activation of XCds1. Thus, the checkpoint-mediated activation of XCds1
      requires phosphorylation by multiple phosphoinositide 3-kinase-related kinases,
      protein-protein dissociation, and autophosphorylation.

PMID- 15509800
TI  - Mechanism of B-cell receptor-induced phosphorylation and activation of
      phospholipase C-gamma2.
AB  - Phospholipase C-gamma2 (PLC-gamma2) plays an important role in B-cell signaling.
      Phosphorylation of various tyrosine residues of PLC-gamma2 has been implicated in
      regulation of its lipase activity. With the use of antibodies specific for each
      of the putative phosphorylation sites, we have now shown that PLC-gamma2 is
      phosphorylated on Y753, Y759, and Y1217 in response to engagement of the B-cell
      receptor in Ramos cells, as well as in murine splenic B cells. In cells
      stimulated maximally via this receptor, the extent of phosphorylation of Y1217
      was three times that of Y753 or of Y759. Stimulation of Jurkat T cells or
      platelets via their immunoreceptors also elicited phosphorylation of Y753 and
      Y759 but not that of Y1217. A basal level of phosphorylation of Y753 was apparent
      in unstimulated lymphocytes. The extent of phosphorylation of Y753 and Y759, but
      not that of Y1217, correlated with the lipase activity of PLC-gamma2. Examination
      of the effects of various pharmacological inhibitors and of RNA interference in
      Ramos cells suggested that Btk is largely, but not completely, responsible for
      phosphorylation of Y753 and Y759, whereas phosphorylation of Y1217 is independent
      of Btk. Finally, phosphorylation of Y1217 and that of Y753 and Y759 occurred on
      different PLC-gamma2 molecules.

PMID- 15509801
TI  - Extracellular signal-regulated kinase 1c (ERK1c), a novel 42-kilodalton ERK,
      demonstrates unique modes of regulation, localization, and function.
AB  - Extracellular signal-regulated kinases (ERKs) are signaling molecules that
      regulate many cellular processes. We have previously identified an alternatively
      spliced 46-kDa form of ERK1 that is expressed in rats and mice and named ERK1b.
      Here we report that the same splicing event in humans and monkeys causes, due to
      sequence differences in the inserted introns, the production of an ERK isoform
      that migrates together with the 42-kDa ERK2. Because of the differences of this
      isoform from ERK1b, we named it ERK1c. We found that its expression levels are
      about 10% of ERK1. ERK1c seems to be expressed in a wide variety of tissues and
      cells. Its activation by MEKs and inactivation by phosphatases are slower than
      those of ERK1, which is probably the reason for its differential regulation in
      response to extracellular stimuli. Unlike ERK1, ERK1c undergoes
      monoubiquitination, which is increased with elevated cell density concomitantly
      with accumulation of ERK1c in the Golgi apparatus. Elevated cell density also
      causes enhanced Golgi fragmentation, which is facilitated by overexpression of
      native ERK1c and is prevented by dominant-negative ERK1c, indicating that ERK1c
      mediates cell density-induced Golgi fragmentation. The differential regulation of
      ERK1c extends the signaling specificity of MEKs after stimulation by various
      extracellular stimuli.

PMID- 15509802
TI  - Requirement of the Mre11 complex and exonuclease 1 for activation of the Mec1
      signaling pathway.
AB  - The large protein kinases, ataxia-telangiectasia mutated (ATM) and ATM-Rad3
      related (ATR), orchestrate DNA damage checkpoint pathways. In budding yeast, ATM
      and ATR homologs are encoded by TEL1 and MEC1, respectively. The Mre11 complex
      consists of two highly related proteins, Mre11 and Rad50, and a third protein,
      Xrs2 in budding yeast or Nbs1 in mammals. The Mre11 complex controls the ATM/Tel1
      signaling pathway in response to double-strand break (DSB) induction. We show
      here that the Mre11 complex functions together with exonuclease 1 (Exo1) in
      activation of the Mec1 signaling pathway after DNA damage and replication block.
      Mec1 controls the checkpoint responses following UV irradiation as well as DSB
      induction. Correspondingly, the Mre11 complex and Exo1 play an overlapping role
      in activation of DSB- and UV-induced checkpoints. The Mre11 complex and Exo1
      collaborate in producing long single-stranded DNA (ssDNA) tails at DSB ends and
      promote Mec1 association with the DSBs. The Ddc1-Mec3-Rad17 complex associates
      with sites of DNA damage and modulates the Mec1 signaling pathway. However, Ddc1
      association with DSBs does not require the function of the Mre11 complex and
      Exo1. Mec1 controls checkpoint responses to stalled DNA replication as well.
      Accordingly, the Mre11 complex and Exo1 contribute to activation of the
      replication checkpoint pathway. Our results provide a model in which the Mre11
      complex and Exo1 cooperate in generating long ssDNA tracts and thereby facilitate
      Mec1 association with sites of DNA damage or replication block.

PMID- 15509803
TI  - Global chromatin structure of 45,000 base pairs of chromosome III in a- and alpha
      cell yeast and during mating-type switching.
AB  - Directionality of yeast mating-type switching has been attributed to differences
      in chromatin structure for the left arm of chromosome III. We have mapped the
      structure of approximately 45 kbp of the left arm of chromosome III in a and
      alpha cells in logarithmically growing cultures and in a cells during switching.
      Distinctive features of chromatin structure were the occurrence of DNase I
      hypersensitive sites in the promoter region of nearly every gene and some
      replication origins and the presence of extended regions of positioned
      nucleosomes in approximately 25% of the open reading frames. Other than the
      recombination enhancer, chromatin structures were identical in the two cell
      types. Changes in chromatin structure during switching were confined to the
      recombination enhancer. This unbiased analysis of an extended region of chromatin
      reveals that significant features of organized chromatin exist for the entire
      region, and these features are largely static with respect to mating type and
      mating-type switching. Our analysis also shows that primary chromatin structure
      does not cause the documented differences in recombinational frequency of the
      left arm of chromosome III in yeast a and alpha cells.

PMID- 15509804
TI  - Regulation of cell cycle-specific gene expression through cyclin-dependent kinase
      mediated phosphorylation of the forkhead transcription factor Fkh2p.
AB  - The forkhead transcription factor Fkh2p acts in a DNA-bound complex with Mcm1p
      and the coactivator Ndd1p to regulate cell cycle-dependent expression of the CLB2
      gene cluster in Saccharomyces cerevisiae. Here, we demonstrate that Fkh2p is a
      target of cyclin-dependent protein kinases and that phosphorylation of Fkh2p
      promotes interactions between Fkh2p and the coactivator Ndd1p. These
      phosphorylation-dependent changes in the Fkh2p-Ndd1p complex play an important
      role in the cell cycle-regulated expression of the CLB2 cluster. Our data
      therefore identify an important regulatory target for cyclin-dependent kinases in
      the cell cycle and further our molecular understanding of the key cell cycle
      regulatory transcription factor Fkh2p.

PMID- 15509805
TI  - Functional role of extranucleosomal DNA and the entry site of the nucleosome in
      chromatin remodeling by ISW2.
AB  - A minimal amount of extranucleosomal DNA was required for nucleosome mobilization
      by ISW2 as shown by using a photochemical histone mapping approach to analyze
      nucleosome movement on a set of nucleosomes with varied lengths of
      extranucleosomal DNA. ISW2 was ineffective in repositioning or mobilizing
      nucleosomes with <or=20 bp of extranucleosomal DNA. In addition, ISW2 was able to
      slide nucleosomes to within only 10 to 13 bp of the edge of DNA fragments. The
      nucleosome mobilization was promoted by extranucleosomal single-stranded DNA with
      modest strand preference. Gaps (10 bp) just inside the nucleosome and in the
      extranucleosomal DNA showed that the transfer of torsional strain (twist) into
      the nucleosomal DNA region was not required for mobilizing nucleosomes. However,
      indications are that the extranucleosomal DNA immediately adjacent to the
      nucleosome has an important role in the initial stage of nucleosome movement by
      ISW2.

PMID- 15509806
TI  - FoxO3a and BCR-ABL regulate cyclin D2 transcription through a STAT5/BCL6
      dependent mechanism.
AB  - Cell cycle arrest by FoxO transcription factors involves transcriptional
      repression of cyclin D, although the exact mechanism remains unclear. In this
      study, we used the BCR-ABL-expressing cell line BV173 as a model system to
      investigate the mechanisms whereby FoxO3a regulates cyclin D2 expression.
      Inhibition of BCR-ABL by STI571 results in down-regulation of cyclin D2
      expression, activation of FoxO3a activity, and up-regulation of BCL6 expression.
      Using reporter gene assays, we demonstrate that STI571, FoxO3a, and BCL6 can
      repress cyclin D2 transcription through a STAT5/BCL6 site located within the
      cyclin D2 promoter. We propose that BCR-ABL inhibition leads to FoxO3a
      activation, which in turn induces the expression of BCL6, culminating in the
      repression of cyclin D2 transcription through this STAT5/BCL6 site. This process
      was verified by mobility shift and chromatin immunoprecipitation analyses. We
      find that conditional activation of FoxO3a leads to accumulation of BCL6 and down
      regulation of cyclin D2 at protein and mRNA levels. Furthermore, silencing of
      FoxO3a and BCL6 in BCR-ABL-expressing cells abolishes STI571-mediated effects on
      cyclin D2. This report establishes the signaling events whereby BCR-ABL signals
      are relayed to cyclin D2 to mediate cell cycle progression and defines a
      potential mechanism by which FoxO proteins regulate cyclin D2 expression.

PMID- 15509807
TI  - NC2alpha interacts with BTAF1 and stimulates its ATP-dependent association with
      TATA-binding protein.
AB  - Transcriptional activity of the TATA-binding protein (TBP) is controlled by a
      variety of proteins. The BTAF1 protein (formerly known as TAF(II)170/TAF-172 and
      the human ortholog of Saccharomyces cerevisiae Mot1p) and the NC2 complex
      composed of NC2alpha (DRAP1) and NC2beta (Dr1) are able to bind to TBP directly
      and regulate RNA polymerase II transcription both positively and negatively.
      Here, we present evidence that the NC2alpha subunit interacts with BTAF1. In
      contrast, the NC2beta subunit is not able to associate with BTAF1 and seems to
      interfere with the BTAF1-TBP interaction. Addition of NC2alpha or the NC2 complex
      can stimulate the ability of BTAF1 to interact with TBP. This function is
      dependent on the presence of ATP in cell extracts but does not involve the ATPase
      activity of BTAF1 nor phosphorylation of NC2alpha. Together, our results
      constitute the first evidence of the physical cooperation between BTAF1 and
      NC2alpha in TBP regulation and provide a framework to understand transcription
      functions of NC2alpha and NC2beta in vivo.

PMID- 15509809
TI  - Clinical implications of obesity with specific focus on cardiovascular disease: a
      statement for professionals from the American Heart Association Council on
      Nutrition, Physical Activity, and Metabolism: endorsed by the American College of
      Cardiology Foundation.
AB  - Obesity adversely affects cardiac function, increases the risk factors for
      coronary heart disease, and is an independent risk factor for cardiovascular
      disease. The risk of developing coronary heart disease is directly related to the
      concomitant burden of obesity-related risk factors. Modest weight loss can
      improve diastolic function and affect the entire cluster of coronary heart
      disease risk factors simultaneously. This statement from the American Heart
      Association Council on Nutrition, Physical Activity, and Metabolism reviews the
      relationship between obesity and the cardiovascular system, evaluates the effect
      of weight loss on coronary heart disease risk factors and coronary heart disease,
      and provides practical weight management treatment guidelines for cardiovascular
      healthcare professionals. The data demonstrate that weight loss and physical
      activity can prevent and treat obesity-related coronary heart disease risk
      factors and should be considered a primary therapy for obese patients with
      cardiovascular disease.

PMID- 15509808
TI  - Interferon regulatory factor 1 binding to p300 stimulates DNA-dependent
      acetylation of p53.
AB  - Interferon regulatory factor 1 (IRF-1) and p53 control distinct sets of
      downstream genes; however, these two antioncogenic transcription factors converge
      to regulate p21 gene expression and to inhibit tumor formation. Here we
      investigate the mechanism by which IRF-1 and p53 synergize at the p21 promoter
      and show that stimulation of p21 transcription by IRF-1 does not require its DNA
      binding activity but relies on the ability of IRF-1 to bind the coactivator p300
      and to stimulate p53-dependent transcription by an allosteric mechanism. Deletion
      of the p300-binding sites in IRF-1 eliminates the ability of IRF-1 to stimulate
      p53 acetylation and associated p53 activity. Complementing this, small peptides
      derived from the IRF-1-p300 interface can bind to p300, stabilize the binding of
      p300 to DNA-bound p53, stimulate p53 acetylation in trans, and up-regulate p53
      dependent activity from the p21 promoter. The nonacetylatable p53 mutant (p53
      6KR) cannot be stimulated by IRF-1, further suggesting that p53 acetylation is
      the mechanism whereby IRF-1 modifies p53 activity. These data expand the core
      p300-p53 protein LXXLL and PXXP interface by including an IRF-1-p300 interface as
      an allosteric modifier of DNA-dependent acetylation of p53 at the p21 promoter.

PMID- 15509810
TI  - Images in clinical medicine. Falciform-ligament sign of pneumoperitoneum.

PMID- 15509811
TI  - Health care coverage and drug costs--the candidates speak out.

PMID- 15509812
TI  - Registration of clinical trials--voluntary or mandatory?

PMID- 15509813
TI  - A precarious exchange.

PMID- 15509814
TI  - Residency regulations--resisting our reflexes.

PMID- 15509815
TI  - Bacterial meningitis--a view of the past 90 years.

PMID- 15509816
TI  - Effect of reducing interns' weekly work hours on sleep and attentional failures.
AB  - BACKGROUND: Knowledge of the physiological effects of extended (24 hours or more)
      work shifts in postgraduate medical training is limited. We aimed to quantify
      work hours, sleep, and attentional failures among first-year residents
      (postgraduate year 1) during a traditional rotation schedule that included
      extended work shifts and during an intervention schedule that limited scheduled
      work hours to 16 or fewer consecutive hours. METHODS: Twenty interns were studied
      during two three-week rotations in intensive care units, each during both the
      traditional and the intervention schedule. Subjects completed daily sleep logs
      that were validated with regular weekly episodes (72 to 96 hours) of continuous
      polysomnography (r=0.94) and work logs that were validated by means of direct
      observation by study staff (r=0.98). RESULTS: Seventeen of 20 interns worked more
      than 80 hours per week during the traditional schedule (mean, 84.9; range, 74.2
      to 92.1). All interns worked less than 80 hours per week during the intervention
      schedule (mean, 65.4; range, 57.6 to 76.3). On average, interns worked 19.5 hours
      per week less (P<0.001), slept 5.8 hours per week more (P<0.001), slept more in
      the 24 hours preceding each working hour (P<0.001), and had less than half the
      rate of attentional failures while working during on-call nights (P=0.02) on the
      intervention schedule as compared with the traditional schedule. CONCLUSIONS:
      Eliminating interns' extended work shifts in an intensive care unit significantly
      increased sleep and decreased attentional failures during night work hours.

PMID- 15509817
TI  - Effect of reducing interns' work hours on serious medical errors in intensive
      care units.
AB  - BACKGROUND: Although sleep deprivation has been shown to impair neurobehavioral
      performance, few studies have measured its effects on medical errors. METHODS: We
      conducted a prospective, randomized study comparing the rates of serious medical
      errors made by interns while they were working according to a traditional
      schedule with extended (24 hours or more) work shifts every other shift (an
      "every third night" call schedule) and while they were working according to an
      intervention schedule that eliminated extended work shifts and reduced the number
      of hours worked per week. Incidents were identified by means of a
      multidisciplinary, four-pronged approach that included direct, continuous
      observation. Two physicians who were unaware of the interns' schedule assignments
      independently rated each incident. RESULTS: During a total of 2203 patient-days
      involving 634 admissions, interns made 35.9 percent more serious medical errors
      during the traditional schedule than during the intervention schedule (136.0 vs.
      100.1 per 1000 patient-days, P<0.001), including 56.6 percent more nonintercepted
      serious errors (P<0.001). The total rate of serious errors on the critical care
      units was 22.0 percent higher during the traditional schedule than during the
      intervention schedule (193.2 vs. 158.4 per 1000 patient-days, P<0.001). Interns
      made 20.8 percent more serious medication errors during the traditional schedule
      than during the intervention schedule (99.7 vs. 82.5 per 1000 patient-days,
      P=0.03). Interns also made 5.6 times as many serious diagnostic errors during the
      traditional schedule as during the intervention schedule (18.6 vs. 3.3 per 1000
      patient-days, P<0.001). CONCLUSIONS: Interns made substantially more serious
      medical errors when they worked frequent shifts of 24 hours or more than when
      they worked shorter shifts. Eliminating extended work shifts and reducing the
      number of hours interns work per week can reduce serious medical errors in the
      intensive care unit.

PMID- 15509818
TI  - Clinical features and prognostic factors in adults with bacterial meningitis.
AB  - BACKGROUND: We conducted a nationwide study in the Netherlands to determine
      clinical features and prognostic factors in adults with community-acquired acute
      bacterial meningitis. METHODS: From October 1998 to April 2002, all Dutch
      patients with community-acquired acute bacterial meningitis, confirmed by
      cerebrospinal fluid cultures, were prospectively evaluated. All patients
      underwent a neurologic examination on admission and at discharge, and outcomes
      were classified as unfavorable (defined by a Glasgow Outcome Scale score of 1 to
      4 points at discharge) or favorable (a score of 5). Predictors of an unfavorable
      outcome were identified through logistic-regression analysis. RESULTS: We
      evaluated 696 episodes of community-acquired acute bacterial meningitis. The most
      common pathogens were Streptococcus pneumoniae (51 percent of episodes) and
      Neisseria meningitidis (37 percent). The classic triad of fever, neck stiffness,
      and a change in mental status was present in only 44 percent of episodes;
      however, 95 percent had at least two of the four symptoms of headache, fever,
      neck stiffness, and altered mental status. On admission, 14 percent of patients
      were comatose and 33 percent had focal neurologic abnormalities. The overall
      mortality rate was 21 percent. The mortality rate was higher among patients with
      pneumococcal meningitis than among those with meningococcal meningitis (30
      percent vs. 7 percent, P<0.001). The outcome was unfavorable in 34 percent of
      episodes. Risk factors for an unfavorable outcome were advanced age, presence of
      otitis or sinusitis, absence of rash, a low score on the Glasgow Coma Scale on
      admission, tachycardia, a positive blood culture, an elevated erythrocyte
      sedimentation rate, thrombocytopenia, and a low cerebrospinal fluid white-cell
      count. CONCLUSIONS: In adults presenting with community-acquired acute bacterial
      meningitis, the sensitivity of the classic triad of fever, neck stiffness, and
      altered mental status is low, but almost all present with at least two of the
      four symptoms of headache, fever, neck stiffness, and altered mental status. The
      mortality associated with bacterial meningitis remains high, and the strongest
      risk factors for an unfavorable outcome are those that are indicative of systemic
      compromise, a low level of consciousness, and infection with S. pneumoniae.

PMID- 15509819
TI  - Multiple myeloma.

PMID- 15509820
TI  - Images in clinical medicine. Pathologic fracture and lytic lesions in multiple
      myeloma.

PMID- 15509821
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 33-2004. A 34-year-old man with a seizure and a frontal-lobe
      brain lesion.

PMID- 15509822
TI  - Awake and informed.

PMID- 15509823
TI  - Doctors and drug companies.

PMID- 15509824
TI  - Financial conflicts of interest in physicians' relationships with the
      pharmaceutical industry--self-regulation in the shadow of federal prosecution.

PMID- 15509825
TI  - Genomics and malaria control.

PMID- 15509826
TI  - Fluid resuscitation in the intensive care unit.

PMID- 15509827
TI  - Doxorubicin-induced myocardial injury.

PMID- 15509828
TI  - Rituximab for rheumatoid arthritis.

PMID- 15509829
TI  - Arterial thrombosis in systemic lupus erythematosus.

PMID- 15509830
TI  - Drug therapy in Alzheimer's disease.

PMID- 15509831
TI  - Dislocation of the lenses.

PMID- 15509832
TI  - Ventricular tachycardia complicating alcohol septal ablation.

PMID- 15509833
TI  - Genomic basis for cell-wall diversity in plants. A comparative approach to gene
      families in rice and Arabidopsis.
AB  - Monocotyledons and dicotyledons are distinct, not only in their body plans and
      developmental patterns, but also in the structural features of their cell walls.
      The recent completion of the rice (Oryza sativa) genomic sequence and publication
      of the sequence data, together with the completed database of the Arabidopsis
      thaliana genome, provide the first opportunity to compare the full complement of
      cell-wall-related genes from the two distinct classes of flowering plants. We
      made this comparison by exploiting the fact that Arabidopsis and rice have type I
      and type II walls, respectively, and therefore represent the two extremes in
      terms of the structural features of plant cell walls. In this review article, we
      classify all cell-wall-related genes into 32 gene families, and generate their
      phylogenetic trees. Using these data, we can phylogenetically compare individual
      genes of particular interest between Arabidopsis and rice. This comparative
      genome approach shows that the differences in wall architecture in the two plant
      groups actually mirror the diversity of the individual gene families involved in
      the cell-wall dynamics of the respective plant species. This study also
      identifies putative rice orthologs of genes with well-defined functions in
      Arabidopsis and other plant species.

PMID- 15509834
TI  - The GURKE gene encoding an acetyl-CoA carboxylase is required for partitioning
      the embryo apex into three subregions in Arabidopsis.
AB  - In Arabidopsis, three major regions, which ultimately develop into the two
      cotyledons, the cotyledon boundaries and the shoot apical meristem (SAM), are
      formed at the apex of the globular stage embryo. To reveal the molecular
      mechanism underlying this pattern formation, we isolated a cotyledon-defective
      mutant from EMS mutagenized lines. This mutant completely lacks cotyledons in the
      most severe cases, and is allelic to gurke (gk), which was previously reported as
      a mutant defective in apical patterning of the embryo. To evaluate the
      morphological effects of the mutation in the GK gene, we investigated the
      expression patterns in gk embryos of SHOOT MERISTEMLESS (STM), AINTEGUMENTA (ANT)
      and CUP-SHAPED COTYLEDON1 (CUC1), which are markers of the SAM, cotyledons and
      cotyledon boundaries, respectively. Expression of all these genes largely
      overlapped in gk, suggesting a failure to partition the apex of the embryo into
      the three subregions. Enlargement of the CUC1 expression domain was also observed
      and may explain the inhibition of cotyledon development in gk. Moreover, we
      cloned the GK gene, and confirmed that it encodes ACC1, an acetyl-CoA carboxylase
      which catalyzes malonyl-CoA synthesis. Our results suggest that metabolites
      derived from malonyl-CoA are required for partitioning of the apical part of the
      embryo.

PMID- 15509835
TI  - Emission of ent-kaurene, a diterpenoid hydrocarbon precursor for gibberellins,
      into the headspace from plants.
AB  - ent-Kaurene is a tetracyclic hydrocarbon precursor for gibberellins (GAs) in
      plants and fungi. To address whether fungal GA biosynthesis enzymes function in
      plants, we generated transgenic Arabidopsis plants overexpressing ent-kaurene
      synthase (GfCPS/KS) from a GA-producing fungus Gibberella fujikuroi. GfCPS/KS
      catalyzes a two-step reaction corresponding to ent-copalyl diphosphate synthase
      (CPS) and ent-kaurene synthase (KS) activities in plants. When GfCPS/KS was
      overexpressed and targeted to plastids, a range of GA-deficient phenotypes of the
      ga1-3 and ga2-1 mutants (defective in CPS and KS, respectively) were restored to
      wild type. Unexpectedly, the transgenic lines overproducing GfCPS/KS emitted the
      GA precursor ent-kaurene into the headspace besides its accumulation in the plant
      body. When co-cultivated with the ent-kaurene overproducers in a closed
      environment, the airborne ent-kaurene was able to fully complement the dwarf
      phenotype of ga1-3 and ga2-1 mutants, but not that of the ga3-1 mutant (defective
      in ent-kaurene oxidase). These results suggest that ent-kaurene may be
      efficiently metabolized into bioactive GAs in Arabidopsis when supplied as a
      volatile. We also provide evidence that ent-kaurene is released in the headspace
      of wild-type Chamaecyparis obtusa and Cryptomeria japonica plants, suggesting the
      occurrence of this hydrocarbon GA precursor as a volatile in nature.

PMID- 15509836
TI  - Mutation of a nitrate transporter, AtNRT1:4, results in a reduced petiole nitrate
      content and altered leaf development.
AB  - Unlike nitrate uptake of plant roots, less is known at the molecular level about
      how nitrate is distributed in various plant tissues. In the present study,
      characterization of the nitrate transporter, AtNRT1:4, revealed a special role of
      petiole in nitrate homeostasis. Electrophysiological studies using Xenopus
      oocytes showed that AtNRT1:4 was a low-affinity nitrate transporter. Whole-mount
      in situ hybridization and RT-PCR demonstrated that AtNRT1:4 was expressed in the
      leaf petiole. In the wild type, the leaf petiole had low nitrate reductase
      activity, but a high nitrate content, indicating that it is the storage site for
      nitrate, whereas, in the atnrt1:4 mutant, the petiole nitrate content was reduced
      to 50-64% of the wild-type level. Moreover, atnrt1:4 mutant leaves were wider
      than wild-type leaves. This study revealed a critical role of AtNRT1:4 in
      regulating leaf nitrate homeostasis, and the deficiency of AtNRT1:4 can alter
      leaf development.

PMID- 15509837
TI  - Ole e 1, the major allergen from olive (Olea europaea L.) pollen, increases its
      expression and is released to the culture medium during in vitro germination.
AB  - Ole e 1 is a well-characterized allergenic protein from olive pollen. This paper
      examines its presence and that of its transcripts during in vitro pollen
      germination and pollen tube growth. A significant increase of the protein was
      detected after the emergence of the pollen tube, whereas part of the protein was
      released into the culture medium throughout pollen germination. A slight increase
      in the number of Ole e 1 transcripts was also detected prior to the described
      rise in the protein level. Within the pollen tube, the allergen was localized in
      the subapical region, mainly in the lumen of endoplasmic reticulum cisternae. Ole
      e 1 was also localized extracellularly in the vicinity of the pollen tube cell
      wall. These findings are discussed regarding the biological role attributed to
      the protein during pollen hydration and pollen tube growth and in terms of their
      importance for the understanding of the allergenic response in humans. On the
      basis of recent findings for the LAT52 protein in tomato, we propose that the
      homologous Ole e 1 protein might participate in a similar signal transduction
      pathway in olive, to control pregermination and pollen tube emergence and
      guidance.

PMID- 15509838
TI  - Storage behavior of Chionanthus retusus seed and asynchronous development of the
      radicle and shoot apex during germination in relation to germination inhibitors,
      including abscisic acid and four phenolic glucosides.
AB  - Studies on seed storage of Chionanthus retusus Lindl. & Paxt. revealed an
      orthodox behavior, one which showed both desiccation and freezing tolerance. An
      epicotyl after-ripening dormancy was expressed in C. retusus seeds by slow growth
      of the shoot apex relative to more rapid growth of the radicle when seeds were
      germinated at 30/20 degrees C. Although these seeds exhibit radicle protrusion,
      they must be after-ripened for another 8-10 weeks at 30/20 degrees C in order to
      obtain normal shoot growth. Removal of the endosperm, however, quickly stimulated
      cotyledon and shoot emergence without the additional after-ripening. Water
      soluble glucoside phenolics, GL-3, Nuzhenide, ligustroside and oleoside dimethyl
      ester are present at relatively high levels in endosperm of freshly harvested
      seeds. These glucoside phenolics are excreted from the endosperm during
      subsequent after-ripening. Embryo and endosperm tissue from seed germinating at
      30/20 degrees C (germination being defined by protrusion of the radicle) had a 10
      times lower abscisic acid (ABA) content than similar tissues from freshly
      harvested mature seed. However, no shoot growth occurred even with the 10-fold
      reduction in ABA and a concomitant increase in endogenous gibberellins A1, A4 and
      A20. Thus, epicotyl dormancy during the first 8 weeks of after-ripening at 30/20
      degrees C may be controlled by factors other than high ABA, i.e., the slow
      development of the shoot apex following radicle protrusion may be controlled more
      by high levels of glucoside phenolics than by diminished ABA and elevated GA
      levels.

PMID- 15509839
TI  - Isolation and characterization of oxygen-evolving photosystem II complexes
      retaining the PsbO, P and Q proteins from Euglena gracilis.
AB  - Oxygen-evolving photosystem II (PSII) complexes of Euglena gracilis were isolated
      and characterized. (1) The PSII complexes contained three extrinsic proteins of
      33 kDa (PsbO), 23 kDa (PsbP) and 17 kDa (PsbQ), and showed oxygen-evolving
      activity of around 700 micromol O2 (mg Chl)(-1) h(-1) even in the absence of Cl-
      and Ca2+ ions. (2) NaCl-treatment removed not only PsbP and PsbQ but also a part
      of PsbO from Euglena PSII, indicating that PsbO binds to Euglena PSII more
      loosely than those of other organisms. Treatments by urea/NaCl, alkaline Tris or
      CaCl2 completely removed the three extrinsic proteins from Euglena PSII. (3) Each
      of the Euglena extrinsic proteins bound directly to PSII independent of the other
      extrinsic proteins, which is similar to the binding properties of the extrinsic
      proteins in a green alga, Chlamydomonas reinhardtii. (4) One of the significant
      features of Euglena PSII is that the oxygen evolution was not enhanced by Ca2+.
      When CaCl2-treated Euglena PSII was reconstituted with PsbO, the oxygen-evolving
      activity was stimulated by the addition of NaCl, but no further stimulation was
      observed by CaCl2. (5) Oxygen evolution of Euglena PSII reconstituted with PsbO
      from C. reinhardtii or spinach instead of that from Euglena also showed no
      enhancement by Ca2+, whereas a significant enhancement of oxygen evolution was
      observed by Ca2+ when the green algal or higher plant PSII was reconstituted with
      Euglena PsbO instead of their own PsbO. These results indicate that the PSII
      intrinsic proteins instead of the extrinsic PsbO protein, are responsible for the
      stimulation of oxygen evolution by Ca2+. Sequence comparison of major PSII
      intrinsic proteins revealed that PsbI of Euglena PSII is remarkably different
      from other organisms in that Euglena PsbI possesses extra 16-17 residues exposed
      to the luminal side. This may be related to the loss of enhancement of oxygen
      evolution by Ca2+ ion.

PMID- 15509840
TI  - Production of polyhydroxybutyrate by polycistronic expression of bacterial genes
      in tobacco plastid.
AB  - Transgenic techniques are used to enhance and improve crop production, and their
      application to the production of chemical resources in plants has been under
      investigation. To achieve this latter goal, multiple-gene transformation is
      required to improve or change plant metabolic pathways; when accomplished by
      plant nuclear transformation, however, this procedure is costly and time
      consuming. We succeeded in the metabolic engineering of the tobacco plant by
      introducing multiple genes within a bacteria-like operon into a plastid genome. A
      tobacco plastid was transformed with a polycistron consisting of the
      spectinomycin resistance gene and three bacterial genes for the biosynthesis of
      the biodegradable polyester, poly[(R)-3-hydroxybutyrate] (PHB), after
      modification of their ribosome binding sites. DNA and RNA analysis confirmed the
      insertion of the introduced genes into the plastid genome and their polycistronic
      expression. As the result, the transplastomic tobacco accumulated PHB in its
      leaves. The introduced genes and the PHB productivity were maternally inherited,
      avoiding genetic spread by pollen diffusion, and were maintained stably in the
      seed progeny. Despite the low PHB productivity, this report demonstrates the
      feasibility of transplastomic technology for metabolic engineering. This "phyto
      fermentation" system can be applied to plant production of various chemical
      commodities and pharmaceuticals.

PMID- 15509841
TI  - Ectopic expression of a UDP-glucose:phenylpropanoid glucosyltransferase leads to
      increased resistance of transgenic tobacco plants against infection with Potato
      Virus Y.
AB  - Transgenic tobacco plants over-expressing a salicylate- and pathogen-inducible
      glucosyltransferase (TOGT) acting on various phenylpropanoids show enhanced
      resistance against infection with potato virus Y (PVY). The transgenic plants are
      characterized by a several-fold increased glucosyltransferase activity in leaves
      as well as in roots. Under non-infectious conditions profiles of phenylpropanoids
      in leaves of transgenic lines were similar to that of controls. Feeding
      experiments with leaf-discs demonstrated a higher capacity for glucosylation of
      the coumarin scopoletin. After inoculation with PVY the transgenic lines showed
      similar formation of necrotic leaf lesions but significantly decreased levels of
      virus coat-protein when compared with control plants. Thus, our results imply
      that the activity of TOGT and the subsequent accumulation of glucosylated
      coumarins represent an important step in the cascade of events resulting in
      confinement of viral pathogens.

PMID- 15509842
TI  - Characterization of a rice nuclear-encoded plastid RNA polymerase gene OsRpoTp.
AB  - We isolated and characterized two rice genes, OsRpoTp and OsRpoTm, that encode
      putative phage-type RNA polymerases. Predicted amino acid sequences showed high
      homology of these genes to known RpoT genes. A transient expression assay using
      green fluorescent protein indicated that the encoded proteins were localized to
      plastids and mitochondria, respectively. We demonstrated by reverse transcription
      PCR experiments and immunoblot analysis that OsRpoTp expression occurred at an
      early stage of leaf development, prior to the transcript accumulation of the
      genes that were transcribed by the nuclear-encoded plastid RNA polymerase (NEP).
      Expression analyses of the chloroplast-deficient rice mutant, virescent-1, showed
      a discrepancy between OsRpoTp protein accumulation and the level of transcripts
      of NEP-transcribed genes. Our results suggest that NEP activation is regulated by
      a process after transcription, and is affected by the developmental state of
      chloroplast biogenesis.

PMID- 15509844
TI  - The Arabidopsis rab5 homologs rha1 and ara7 localize to the prevacuolar
      compartment.
AB  - Rha1, an Arabidopsis Rab5 homolog, plays a critical role in vacuolar trafficking
      in plant cells. In this study, we investigated the localization of Rha1 and Ara7,
      two Arabidopsis proteins that have highly similar amino acid sequence homology to
      Rab5 in animal cells. Both Ara7 and Rha1 gave a punctate staining pattern and
      colocalized when transiently expressed as GFP- (green fluorescent protein) or
      small epitope-tagged forms in Arabidopsis protoplasts. In protoplasts,
      transiently expressed Rha1 and Ara7 colocalized with AtPEP12p and VSR(At-1), two
      proteins that are known to be present at the prevacuolar compartment (PVC).
      Furthermore, endogenous Rha1 also gave a punctate staining pattern and
      colocalized with AtPEP12p to the PVC. Mutations in the first and second GTP
      binding motifs alter the localizations of GFP: Rha1[S24N] in the cytosol and
      Rha1[Q69L] in the tonoplast of the central vacuole. Also, mutations in the
      effector domain and the prenylation site inhibit membrane association of Rha1.
      Based on these results, we propose that Rha1 and Ara7 localize to the PVC and
      that GTP-binding motifs as well as the effector domain are important for
      localization of Rha1 to the PVC.

PMID- 15509843
TI  - Plasma membrane H(+)-ATPase and 14-3-3 isoforms of Arabidopsis leaves: evidence
      for isoform specificity in the 14-3-3/H(+)-ATPase interaction.
AB  - The plasma membrane H(+)-ATPase is activated by binding of 14-3-3 protein to the
      phosphorylated C terminus. Considering the large number of 14-3-3 and H(+)-ATPase
      isoforms in Arabidopsis (13 and 11 expressed genes, respectively), specificity in
      binding may exist between 14-3-3 and H(+)-ATPase isoforms. We now show that the
      H(+)-ATPase is the main target for 14-3-3 binding at the plasma membrane, and
      that all twelve 14-3-3 isoforms tested bind to the H(+)-ATPase in vitro. Using
      specific antibodies for nine of the 14-3-3 isoforms, we show that GF14epsilon,
      mu, lambda, omega, chi, phi, nu, and upsilon are present in leaves, but that
      isolated plasma membranes lack GF14chi, phi and upsilon. Northern blots using
      isoform-specific probes for all 14-3-3 and H(+)-ATPase isoforms showed that
      transcripts were present for most of the isoforms. Based on mRNA levels,
      GF14epsilon, mu, lambda and chi are highly expressed 14-3-3 isoforms, and AHA1,
      3, and 11 highly expressed H(+)-ATPase isoforms in leaves. However, mass peptide
      fingerprinting identified AHA1 and 2 with the highest score, and their presence
      could be confirmed by MS/MS. It may be calculated that under 'unstressed'
      conditions less than one percent of total 14-3-3 is attached to the H(+)-ATPase.
      However, during a condition requiring full activation of H+ pumping, as induced
      here by the presence of the fungal toxin fusicoccin, several percent of total 14
      3-3 may be engaged in activation of the H(+)-ATPase.

PMID- 15509845
TI  - High-intensity-light-dependent and transient expression of new genes encoding
      distant relatives of light-harvesting chlorophyll-a/b proteins in Chlamydomonas
      reinhardtii.
AB  - We identified four Lhc-like genes (Lhl) encoding proteins that are distant
      relatives of light-harvesting chlorophyll a/b-binding (LHC) proteins in the green
      alga Chlamydomonas reinhardtii. Their mRNA levels after transfer from low
      intensity light to high-intensity light (HL) were examined and compared with
      those of Lhc genes encoding LHC proteins of PSII. The transfer caused a decrease
      in the mRNA level of Lhl3, a homolog of Arabidopsis thaliana Lil3, within 2 h,
      followed by gradual restoration depending on the intensity of HL. The response
      was similar to that of Lhc genes. In contrast, the mRNA levels of Lhl1, Lhl2 and
      Lhl4 significantly increased, reached a maximum within 1 h after the transfer and
      then rapidly returned to a low level. The intensity of HL little influenced the
      response of these genes. While the Lhl1 and Lhl2 proteins were homologs of early
      light-inducible protein (ELIP) and high-light-inducible protein (HLIP),
      respectively, Lhl4 encoded a novel protein. The HL-induced expression of Lhl4 was
      most prominent among the genes tested. Studies using various inhibitors indicate
      that the HL response is not mediated by the redox state of plastoquinone pool or
      reactive oxygen species, but required de novo protein synthesis in the cytosol.

PMID- 15509846
TI  - Characterization of a 200 kDa microtubule-associated protein of tobacco BY-2
      cells, a member of the XMAP215/MOR1 family.
AB  - A microtubule-associated protein composed of a 200 kDa polypeptide (MAP200) was
      isolated from tobacco-cultured BY-2 cells. Analysis of the partial amino acid
      sequence showed that MAP200 was identical to TMBP200, the tobacco MOR1/XMAP215
      homolog. Although several homolog proteins in animal and yeast cells have been
      reported to promote MT dynamics in vitro, no such function has been reported for
      plant homologs. Turbidity measurements of tubulin solution suggested that MAP200
      promoted tubulin polymerization, and analysis by dark-field microscopy revealed
      that this MAP increased both the number and length of microtubules (MTs).
      Electron microscopy and experiments using a chemical crosslinker demonstrated
      that MAP200 forms a complex with tubulin. Throughout the cell cycle, some MAP200
      colocalized with MT structures, including cortical MTs, the preprophase band,
      spindle and phragmoplast, while some MAP200 was localized in areas lacking MTs.
      Based on our biochemical and immunofluorescence findings, the function of MAP200
      in MT polymerization is discussed.

PMID- 15509847
TI  - Inactivation of ycf33 results in an altered cyclic electron transport pathway
      around photosystem I in Synechocystis sp. PCC6803.
AB  - ycf33 encodes a small protein with a molecular mass of 7.5 kDa and is found from
      cyanobacteria to higher plants. A ycf33 deletion mutant was constructed in
      Synechocystis sp. PCC6803 and characterized. The mutant showed a higher
      phycobilisome/chlorophyll ratio than the wild type and a higher photosystem
      II/photosystem I fluorescence ratio measured at 77 K. Under photoautotrophic
      conditions, the growth rates were not much different from those of the wild type.
      Cyclic electron transport activities around photosystem I were not much different
      between the wild type and the mutant. However, the effects of
      diphenyleneiodonium, an inhibitor of flavoprotein, on cyclic electron transport
      in the mutant were different from those in the wild type; it was severely
      inhibited in the wild type but not much in the mutant. Together with the effects
      of nitrite, which accepts electrons from ferredoxin via nitrite reductase and
      those of HgCl2, it was suggested that the pathway of cyclic electron transport is
      altered in the mutant.

PMID- 15509848
TI  - Cytokinins induce photomorphogenic development in dark-grown gametophytes of
      Ceratopteris richardii.
AB  - The cytokinins benzylaminopurine, kinetin and isopentenyladenine induce
      photomorphogenesis in dark-grown gametophytes of the fern Ceratopteris richardii.
      At sub-nanomolar concentrations each altered the rate and pattern of cell
      division, elongation and differentiation, mimicking aspects of the light-mediated
      transition from filamentous to prothallial growth. Untreated dark-grown
      gametophytes grow as narrow, elongate, asexual filaments with an apical meristem.
      Cytokinin treatments as low as 10(-12) M reduced the length-to-width ratio
      through decreased cell elongation, increased periclinal cell division and induced
      the formation of rhizoid initials in the cells immediately below the apical
      meristem. Higher concentrations (10(-9)-10(-8) M) induced conversion of the
      meristem from apical to notch morphology. Cytokinins induced both red- and blue
      light-mediated photomorphogenic events, suggesting stimulation of both
      phytochrome and cryptochrome signaling; however, cytokinin treatment only
      partially substituted for light in that it did not induce hermaphroditic sexual
      development or spore germination in the dark. Additionally, cytokinins did not
      increase chlorophyll synthesis in dark-grown gametophytes, which unlike
      angiosperms are able to produce mature chloroplasts in the dark. Cytokinin
      treatment had only slight effects on light-grown gametophytes. These results
      suggest evolutionary conservation between angiosperms and pteridophytes in the
      role of cytokinins in regulating photomorphogenesis.

PMID- 15509849
TI  - Activation of phospholipase D induced by hydrogen peroxide in suspension-cultured
      rice cells.
AB  - Hydrogen peroxide (H2O2) (10-100 microM) induced rapid and transient accumulation
      of phosphatidic acid (PA) in suspension-cultured rice cells. When phospholipase
      activity in the cellular extract fraction prepared from rice cells treated with
      H2O2 was assayed in the presence of 1-butanol (0.1%), rapid and transient
      phosphatidylbutanol (PtdBut) formation was observed. Thus, the H2O2-activated
      phospholipase was concluded to be phospholipase D (PLD). Furthermore, H2O2
      directly induced in vitro PLD activation in the cytosolic fraction without H2O2
      treatment. In vitro and in vivo activation of PLD were completely suppressed in
      the presence of lavendustin A (0.05 mM), a potent inhibitor of protein tyrosine
      kinase. Phytoalexin biosynthesis induced by N-acetylchitooligosaccharide elicitor
      was enhanced in the presence of H2O2 (10-100 microM), whereas it was suppressed
      in the presence of tiron, a potent scavenger of O2-, 1-butanol (0.1%) and
      lavendustin A (0.05 mM). These results indicate that H2O2-inducible PLD
      activation enhances signal transduction leading to phytoalexin biosynthesis in
      rice cells.

PMID- 15509850
TI  - Feedback inhibition of spinach L-galactose dehydrogenase by L-ascorbate.
AB  - We have studied the enzymological properties of L-galactose dehydrogenase (l
      GalDH), a key enzyme in the biosynthetic pathway of l-ascorbate (AsA) in plants.
      L-GalDH was purified approximately 560-fold from spinach leaves. The enzyme was a
      homodimer with a subunit mass of 36 kDa. We also cloned the full-length cDNA of
      spinach L-GalDH, which contained an open reading frame encoding 322 amino acid
      residues with a calculated molecular mass of 35,261 Da. The deduced amino acid
      sequence of the cDNA showed 82, 79 and 75% homology to L-GalDH from kiwifruit,
      apple and Arabidopsis, respectively. Recombinant enzyme expressed from the cDNA
      in Escherichia coli showed L-GalDH activity. Southern blot analysis revealed that
      the spinach L-GalDH gene occurs in a single copy. Northern blot analysis suggests
      that L-GalDH is expressed in different organs of spinach. The purified native L
      GalDH showed high specificity for L-galactose with a Km of 116.2+/-3.2 microM.
      Interestingly, spinach L-GalDH exhibited reversible inhibition by AsA, the end
      product of the biosynthetic pathway. The inhibition kinetics indicated a linear
      competitive inhibition with a Ki of 133.2+/-7.2 microM, suggesting feedback
      regulation in AsA synthesis in the plant.

PMID- 15509852
TI  - Dihydroflavonol 4-reductase cDNA from non-anthocyanin-producing species in the
      Caryophyllales.
AB  - Two types of red pigment, anthocyanins and betacyanins, never occur together in
      the same plant. Although anthocyanins are widely distributed in higher plants as
      flower and fruit pigments, betacyanins have replaced anthocyanins in the
      Caryophyllales. We isolated cDNAs encoding dihydroflavonol 4-reductase (DFR),
      which is the first enzyme committed to anthocyanin biosynthesis in the flavonoid
      pathway, from Spinacia oleracea and Phytolacca americana, plants that belong to
      the Caryophyllales. The deduced amino acid sequence of Spinacia DFR and
      Phytolacca DFR revealed a high degree of homology with DFRs of anthocyanin
      producing plants. The DFR of carnation, an exception in the Caryophyllales that
      synthesizes anthocyanin, showed the highest level of identity. In the
      phylogenetic tree, Spinacia DFR and Phytolacca DFR clustered with the DFRs of
      anthocyanin-synthesizing dicots. Recombinant Spinacia and Phytolacca DFRs
      expressed in Escherichia coli convert dihydroflavonol to leucoanthocyanidin. The
      expression and function of DFR in spinach and pokeweed are discussed in relation
      to the molecular evolution of red pigment biosynthesis in higher plants.

PMID- 15509853
TI  - Two cytokinin receptors of Arabidopsis thaliana, CRE1/AHK4 and AHK3, differ in
      their ligand specificity in a bacterial assay.
AB  - Strains of Escherichia coli that express two different cytokinin receptors of
      Arabidopsis thaliana, CRE1/AHK4 and AHK3, were used to study the relative
      sensitivity of these receptors to various cytokinins. Both receptors were most
      sensitive to the bases of the isoprenoid-type cytokinins trans-zeatin and
      isopentenyladenine but differed significantly in the recognition of other
      cytokinin compounds. In particular, CRE1/AHK4 recognized at 1 microm
      concentration only trans-zeatin while AHK3 recognized cis-zeatin and
      dihydrozeatin as well, although with a lower sensitivity. Similarly, CRE1/AHK4
      was not activated by cytokinin ribosides and ribotides, but AHK3 was. Comparisons
      using the ARR5::GUS fusion gene as a cytokinin reporter in Arabidopsis showed
      similar relative degrees of responses in planta, except that cytokinins with
      aromatic side chains showed much higher activities than in the bacterial assay.
      These results indicate that the diverse cytokinin compounds might have specific
      functions in the numerous cytokinin-regulated processes, which may depend in turn
      on different receptors and their associated signalling pathways. The importance
      of precise control of local concentrations of defined cytokinin metabolites to
      regulate the respective downstream event is corroborated.

PMID- 15509854
TI  - Cadmium activates a mitogen-activated protein kinase gene and MBP kinases in
      rice.
AB  - Mitogen-activated protein kinase (MAPK) pathways are modules involved in the
      transduction of extracellular signals to intracellular targets in all eukaryotes.
      In plants, it has been evidenced that MAPKs play a role in the signaling of
      biotic and abiotic stresses, plant hormones, and cell cycle cues. However, the
      effect of heavy metals on plant MAPKs has not been well examined. The Northern
      blot analysis of OsMAPK mRNA levels has shown that only OsMAPK2, but not OsMAPK3
      and OsMAPK4, expressed in suspension-cultured cells in response to 100-400 microM
      Cd treatments. The OsMAPK2 transcripts increased within 12 h upon 400 microM Cd
      treatment. In addition, we found that 42- and 50-kDa MBP kinases were
      significantly activated by Cd treatment in rice suspension-cultured cells. And 40
      , 42-, 50- and 64-kDa MBP kinases were activated in rice roots. Furthermore, GSH
      inhibits Cd-induced 40-kDa MBP kinase activation. By immunoblot analysis and
      immunoprecipitation followed by in-gel kinase assay, we confirmed that Cd
      activated 42-kDa MBP kinase is a MAP kinase. Our results suggest that a MAP
      kinase cascade may function in the Cd-signalling pathway in rice.

PMID- 15509855
TI  - Functional identification of the glycerol transport activity of Chlamydomonas
      reinhardtii CrMIP1.
AB  - By searching a Chlamydomonas expressed sequence tag database and by comparing the
      retrieved data with homologous sequences from a DNA database, we identified an
      expressed Chlamydomonas reinhardtii putative major intrinsic protein (MIP) gene.
      The nucleotide sequence, consisting of 1,631 bp, contains an open reading frame
      coding for a 300-amino-acid protein named CrMIP1. It possesses conserved NPA
      motifs, but is not highly homologous to known aquaporins. CrMIP1 was expressed in
      Saccharomyces cerevisiae and assayed for water and glycerol transport activity.
      By the stopped-flow spectrophotometric assay, CrMIP1 did not enhance the osmotic
      water permeability of membrane vesicles of the yeast transformant. However, the
      transformant cells showed glycerol transport activity in the in vivo assay using
      [14C]glycerol. This is the first report on the isolation and functional
      identification of a MIP member from algae.

PMID- 15509856
TI  - Constitutive expression of a PR10 protein enhances the germination of Brassica
      napus under saline conditions.
AB  - Pathogenesis-related (PR) proteins are expressed by virtually all plants in
      response to pathogen infection and, in many cases, in response to abiotic
      stresses as well and include the PR10 family. However, the precise roles of the
      PR10 protein family in abiotic stress responses are not clear. In this paper we
      report, for the first time, that the constitutive expression of a pea PR10 gene
      in Brassica napus enhances their germination and growth in the presence of NaCl.
      Our findings are discussed within the context of PR10 protein function and their
      utility in engineering stress tolerant crops.

PMID- 15509857
TI  - Requirement of carotene isomerization for the assembly of photosystem II in
      Synechocystis sp. PCC 6803.
AB  - Carotene isomerase mutant (crtH mutant) cells of Synechocystis sp. PCC 6803 can
      accumulate beta-carotene under light conditions. However, the mutant cells grown
      under a light-activated heterotrophic growth condition contained detectable
      levels of neither beta-carotene nor D1 protein of the photosystem (PS) II
      reaction center, and no oxygen-evolving activity of PSII was detected. beta
      Carotene and D1 protein appeared and a high level of PSII activity was detected
      after the cells were transferred to a continuous light condition. The PSI
      activities of thylakoid membranes from mutant cells were almost the same as those
      of thylakoid membranes from wild-type cells, both before and after transfer to
      the continuous light condition. These results suggest that beta-carotene is
      required for the assembly of PSII but not for that of PSI.

PMID- 15509851
TI  - A comprehensive gene expression analysis toward the understanding of growth and
      differentiation of tobacco BY-2 cells.
AB  - To understand how plant cell changes gene expression during cell division and
      after termination of cell division, we analyzed the change of gene expression
      during the growth of tobacco BY-2 cell lines using a cDNA microarray, which
      contained about 9,200 expression sequence tag fragments and corresponded to about
      7,000 genes. We found that log phase cells predominantly expressed DNA/chromosome
      duplication gene homologs. In addition, many genes for basic transcription and
      translation machineries, as well as proteasomal genes, were up-regulated at the
      log phase. About half of the kinesin homolog genes, but not myosin homolog genes,
      were predominantly expressed at the dividing phase as well. In contrast,
      stationary phase cells expressed genes for many receptor kinases, signal
      transduction machineries and transcription factors. Several hundreds of genes
      showed differential expression after incubation of stationary phase cells with
      medium containing either salicylic acid or abscisic acid. These findings
      suggested that BY-2 cells at the stationary phase express genes for perceiving
      extracellular signals.

PMID- 15509858
TI  - Low concentrations of propyzamide and oryzalin alter microtubule dynamics in
      Arabidopsis epidermal cells.
AB  - Previous studies showed that sub-micromolar concentrations of the microtubule
      targeting herbicide propyzamide cause a right-handed helical arrangement of
      cortical microtubule arrays and left-handed twisting in elongating Arabidopsis
      epidermal cells. When seedlings were grown in the presence of 1-2 microM
      propyzamide or 50-100 nM oryzalin, we show that microtubules spent more time in a
      paused state in which they exhibited little net change in length. The drug
      treatment also resulted in slower growth and shortening velocities, increased
      catastrophe, and an overall decrease in microtubule turnover. A reduction in
      microtubule dynamic turnover may underlie the drug-induced rearrangement of
      cortical arrays.

PMID- 15509859
TI  - His-404 and His-405 are essential for enzyme catalytic activities of a bacterial
      indole-3-acetyl-L-aspartic acid hydrolase.
AB  - Bacterial indole-3-acetyl-l-aspartic acid (IAA-Asp) hydrolase has shown very high
      substrate specificity compared with similar IAA-amino acid hydrolase enzymes
      found in Arabidopsis thaliana. The IAA-Asp hydrolase also exhibits, relative to
      the Arabidopsis thaliana-derived enzymes, a very high Vmax (fast reaction rate)
      and a higher Km (lower substrate affinity). These two characteristics indicate
      that there are fundamental differences in the catalytic activity between this
      bacterial enzyme and the Arabidopsis enzymes. By employing a computer simulation
      approach, a catalytic residue, His-385, from a non-sequence-related zinc
      dependent exopeptidase of Pseudomonas was found to structurally match His-405 of
      IAA-Asp hydrolase. The His-405 residue is conserved in all related sequences of
      bacteria and Arabidopsis. Point mutation experiments of this His-405 to seven
      different amino acids resulted in complete elimination of enzyme activity.
      However, point mutation on the neighboring His-404 to eight other residues
      resulted in reduction, to various degrees, of enzyme activity. Amino acid
      substitutions for His-404 also showed that this residue influenced the minor
      activity of the IAA-Asp hydrolase for the substrates IAA-Gly, IAA-Ala, IAA-Ser,
      IAA-Glu and IAA-Asn. These results show the value and potential of structural
      modeling for predicting target residues for further study and for directing
      bioengineering of enzyme structure and function.

PMID- 15509860
TI  - The motility of Chara corallina myosin was inhibited reversibly by 2,3
      butanedione monoxime (BDM).
AB  - We studied the effects of 2,3-butanedione monoxime (BDM) on the cytoplasmic
      streaming of Chara corallina and on the motility of myosin prepared from the same
      plant to examine whether this reagent really affects the plant class XI myosin.
      It was found that BDM inhibited both cytoplasmic streaming and the motility of
      myosin at a very similar concentration range (10-100 mM). BDM introduced directly
      into tonoplast-free cells also inhibited cytoplasmic streaming. These results
      suggested that effect of BDM on cytoplasmic streaming was exerted through myosin
      and not through ion channels at least in Chara corallina, though a very high
      concentration of BDM was required.

PMID- 15509861
TI  - Rho signalling at a glance.

PMID- 15509862
TI  - Penelope Jeggo.

PMID- 15509863
TI  - The dynamic kinetochore-microtubule interface.
AB  - The kinetochore is a control module that both powers and regulates chromosome
      segregation in mitosis and meiosis. The kinetochore-microtubule interface is
      remarkably fluid, with the microtubules growing and shrinking at their point of
      attachment to the kinetochore. Furthermore, the kinetochore itself is highly
      dynamic, its makeup changing as cells enter mitosis and as it encounters
      microtubules. Active kinetochores have yet to be isolated or reconstituted, and
      so the structure remains enigmatic. Nonetheless, recent advances in genetic,
      bioinformatic and imaging technology mean we are now beginning to understand how
      kinetochores assemble, bind to microtubules and release them when the connections
      made are inappropriate, and also how they influence microtubule behaviour. Recent
      work has begun to elucidate a pathway of kinetochore assembly in animal cells;
      the work has revealed that many kinetochore components are highly dynamic and
      that some cycle between kinetochores and spindle poles along microtubules.
      Further studies of the kinetochore-microtubule interface are illuminating: (1)
      the role of the Ndc80 complex and components of the Ran-GTPase system in
      microtubule attachment, force generation and microtubule-dependent inactivation
      of kinetochore spindle checkpoint activity; (2) the role of chromosomal passenger
      proteins in the correction of kinetochore attachment errors; and (3) the function
      of microtubule plus-end tracking proteins, motor depolymerases and other proteins
      in kinetochore movement on microtubules and movement coupled to microtubule
      poleward flux.

PMID- 15509864
TI  - The AMP-activated protein kinase pathway--new players upstream and downstream.
AB  - The AMP-activated protein kinase (AMPK) cascade is a sensor of cellular energy
      status. Whenever the cellular ATP:ADP ratio falls, owing to a stress that
      inhibits ATP production or increases ATP consumption, this is amplified by
      adenylate kinase into a much larger increase in the AMP:ATP ratio. AMP activates
      the system by binding to two tandem domains on the gamma subunits of AMPK, and
      this is antagonized by high concentrations of ATP. AMP binding causes activation
      by a sensitive mechanism involving phosphorylation of AMPK by the tumour
      suppressor LKB1. Once activated, AMPK switches on catabolic pathways that
      generate ATP while switching off ATP-consuming processes. As well as acting at
      the level of the individual cell, the system also regulates food intake and
      energy expenditure at the whole body level, in particular by mediating the
      effects of hormones and cytokines such as leptin, adiponectin and ghrelin. A
      particularly interesting downstream target recently identified is TSC2 (tuberin).
      The LKB1-->AMPK-->TSC2 pathway negatively regulates the target of rapamycin
      (TOR), and this appears to be responsible for limiting protein synthesis and cell
      growth, and protecting against apoptosis, during cellular stresses such as
      glucose starvation.

PMID- 15509866
TI  - Fkh2p and Sep1p regulate mitotic gene transcription in fission yeast.
AB  - In the fission yeast Schizosaccharomyces pombe, several genes including cdc15+,
      spo12+, fin1+, slp1+, ace2+ and plo1+ are periodically expressed during M phase.
      The products of these genes control various aspects of cell cycle progression
      including sister chromatid separation, septation and cytokinesis. We demonstrate
      that periodic expression of these genes is regulated by a common promoter
      sequence element, named a PCB. In a genetic screen for cell cycle regulators we
      have identified a novel forkhead transcription factor, Fkh2p, which is
      periodically phosphorylated in M phase. We show that Fhk2p and another forkhead
      transcription factor, Sep1p, are necessary for PCB-driven M-phase-specific
      transcription. In a previous report we identified a complex by electrophoretic
      mobility shift assay, which we termed PBF, that binds to a 150 bp region of the
      cdc15+ promoter that contains the PCB element. We have identified Mbx1p, a novel
      MADS box protein, as a component of PBF. However, although Mbx1p is periodically
      phosphorylated in M phase, Mbx1p is not required for periodic gene transcription
      in M phase. Moreover, although PBF is absent in strains bearing a C-terminal
      epitope tag on Fkh2p, simultaneous deletion of fkh2+ and sep1+ does not abolish
      PBF binding activity. This suggests that Mbx1p binds to gene promoters, but is
      not required for transcriptional activation. Together these results suggest that
      the activation of the Fkh2p and Sep1p forkhead transcription factors triggers
      mitotic gene transcription in fission yeast.

PMID- 15509865
TI  - The p150-Glued Ssm4p regulates microtubular dynamics and nuclear movement in
      fission yeast.
AB  - During vegetative growth of the fission yeast Schizosaccharomyces pombe,
      microtubules nucleate from multiple microtubule organising centres (MTOCs) close
      to the nucleus, polymerising until they reach the end of the cell and then
      shrinking back to the cell centre. In response to mating pheromone, S. pombe
      undergoes a morphological switch from a vegetative to a shmooing growth pattern.
      The switch in growth mode is paralleled by a switch in microtubular dynamics.
      Microtubules nucleate mostly from a single MTOC and pull on the ends of the cell
      to move the nucleus back and forth. This movement continues after cellular and
      nuclear fusion in the zygote and is important to ensure correct chromosome
      pairing, recombination and segregation during meiosis. Here we show that Ssm4p, a
      p150-Glued protein, is induced specifically in response to pheromone and is
      required for this nuclear movement. Ssm4p is associated with the cytoplasmic
      dynein complex and together with the CLIP-170 homologue Tip1p regulates dynein
      heavy chain localisation. We also show that Ssm4p collaborates with Tip1p in
      establishing the shmooing microtubular array.

PMID- 15509867
TI  - The rat liver peroxisomal membrane forms a permeability barrier for cofactors but
      not for small metabolites in vitro.
AB  - The functional role of the peroxisomal membrane as a permeability barrier to
      metabolites has been a matter of controversy for more than four decades. The
      initial conception, claiming free permeability of the membrane to small solute
      molecules, has recently been challenged by several observations suggesting that
      the peroxisomal membrane forms a closed compartment. We have characterized in
      vitro the permeability of rat liver peroxisomal membrane. Our results indicate
      that the membrane allows free access into peroxisomes for small hydrophilic
      molecules, such as substrates for peroxisomal enzymes (glycolate, urate), but not
      to more bulky cofactors (NAD/H, NADP/H, CoA). Although access for cofactors is
      not prevented completely by the membrane, the membrane barrier severely restricts
      their rate of entry into peroxisomes. The data lead to conclusion that, in vivo,
      peroxisomes may possess their own pool of cofactors, while they share a common
      pool of small metabolites with the cytoplasm. The results also indicate that
      molecular size plays an important role in in vivo distinction between cofactors
      and metabolic intermediates.

PMID- 15509868
TI  - Two clustered 8-oxo-7,8-dihydroguanine (8-oxodG) lesions increase the point
      mutation frequency of 8-oxodG, but do not result in double strand breaks or
      deletions in Escherichia coli.
AB  - Multiply damaged sites (MDSs) are generated in DNA by ionizing radiation. In
      vitro studies predict that base excision repair in cells will convert MDSs to
      lethal double strand breaks (DSBs) when two opposing base damages are situated
      >/=2 bp apart. If the lesions are situated immediately 5' or 3' to each other,
      repair is predicted to occur sequentially due to inhibition of the DNA
      glycosylase by a single strand break repair intermediate. In this study, we
      examined how the distance between two opposing lesions alters the mutation
      frequency of an 8-oxodG in an MDS, and whether repair generates DSBs and
      deletions in bacteria. The 8-oxodG mutation frequency declined in MutY-deficient
      bacteria when the opposing 8-oxodG was 6 bp away, and was similar to a single 8
      oxodG when the lesions were separated by 14 bp. However, the number of deletions
      detected for the MDSs was equivalent to the undamaged sequence. Using a separate
      assay, MDSs consisting of two 8-oxodG or an 8-oxodG opposite a uracil were not
      converted to DSBs in the absence of DNA replication in wild-type and
      transcription-coupled repair-deficient bacteria. This is the first study showing
      that DSB-repair intermediates and deletions are not formed during repair of
      clustered 8-oxodGs in cells.

PMID- 15509869
TI  - Dnmt1 deficiency leads to enhanced microsatellite instability in mouse embryonic
      stem cells.
AB  - DNA hypomethylation is frequently seen in cancer and imparts genomic instability
      in mouse models and some tissue culture systems. However, the effects of genomic
      DNA hypomethylation on mutation rates are still elusive. We have developed a
      model system to analyze the effects of DNA methyltransferase 1 (Dnmt1) deficiency
      on DNA mismatch repair (MMR) in mouse embryonic stem (ES) cells. We generated
      sibling ES cell clones with and without functional Dnmt1 expression, containing a
      stable reporter gene that allowed us to measure the slippage rate at a
      mononucleotide repeat. We found that Dnmt1 deficiency led to a 7-fold increase in
      the microsatellite slippage rate. Interestingly, the region flanking the
      mononucleotide repeat was unmethylated regardless of Dnmt1 status, suggesting
      that it is not the local levels of DNA methylation that direct the increase in
      microsatellite instability (MSI). The enhanced MSI was associated with higher
      levels of histone H3 acetylation and lower MeCP2 binding at regions near the
      assayed microsatellite, suggesting that Dnmt1 loss may decrease MMR efficiency by
      modifying chromatin structure.

PMID- 15509872
TI  - Stuck in the skin. Blood fats waylay immune cells.

PMID- 15509870
TI  - Multiple defects in translation associated with altered ribosomal protein L4.
AB  - The ribosomal proteins L4 and L22 form part of the peptide exit tunnel in the
      large ribosomal subunit. In Escherichia coli, alterations in either of these
      proteins can confer resistance to the macrolide antibiotic, erythromycin. The
      structures of the 30S as well as the 50S subunits from each antibiotic resistant
      mutant differ from wild type in distinct ways and L4 mutant ribosomes have
      decreased peptide bond-forming activity. Our analyses of the decoding properties
      of both mutants show that ribosomes carrying the altered L4 protein support
      increased levels of frameshifting, missense decoding and readthrough of stop
      codons during the elongation phase of protein synthesis and stimulate utilization
      of non-AUG codons and mutant initiator tRNAs at initiation. L4 mutant ribosomes
      are also altered in their interactions with a range of 30S-targeted antibiotics.
      In contrast, the L22 mutant is relatively unaffected in both decoding activities
      and antibiotic interactions. These results suggest that mutations in the large
      subunit protein L4 not only alter the structure of the 50S subunit, but upon
      subunit association, also affect the structure and function of the 30S subunit.

PMID- 15509873
TI  - Prey for long life. The hunted don't necessarily age quickly.

PMID- 15509871
TI  - Application of locked nucleic acids to improve aptamer in vivo stability and
      targeting function.
AB  - Aptamers are powerful candidates for molecular imaging applications due to a
      number of attractive features, including rapid blood clearance and tumor
      penetration. We carried out structure-activity relationship (SAR) studies with
      the Tenascin-C binding aptamer TTA1, which is a promising candidate for
      application in tumor imaging with radioisotopes. The aim was to improve its in
      vivo stability and target binding. We investigated the effect of thermal
      stabilization of the presumed non-binding double-stranded stem region on binding
      affinity and resistance against nucleolytic degradation. To achieve maximal
      thermal stem stabilization melting experiments with model hexanucleotide duplexes
      consisting of unmodified RNA, 2'-O-methyl RNA (2'-OMe), 2'-Fluoro RNA (2'-F) or
      Locked Nucleic Acids (LNAs) were initially carried out. Extremely high melting
      temperatures have been found for an LNA/LNA duplex. TTA1 derivatives with LNA and
      2'-OMe modifications within the non-binding stem have subsequently been
      synthesized. Especially, the LNA-modified TTA1 derivative exhibited significant
      stem stabilization and markedly improved plasma stability while maintaining its
      binding affinity to the target. In addition, higher tumor uptake and longer blood
      retention was found in tumor-bearing nude mice. Thus, our strategy to introduce
      LNA modifications after the selection procedure is likely to be generally
      applicable to improve the in vivo stability of aptamers without compromising
      their binding properties.

PMID- 15509874
TI  - The goldilocks genes. Our chromosomes can get sloppy and delete or pick up genes.
      Researchers are starting to probe how these DNA miscues affect health and
      longevity.

PMID- 15509875
TI  - Validity and reliability of the Huet questionnaire to assess maximal oxygen
      uptake.
AB  - The usual fitness tests available to assess maximal oxygen uptake (VO2max), a key
      fitness component, are not particularly useful for epidemiological studies.
      Questionnaires to assess VO2max, however, are simple, easy to use, and
      inexpensive. In 1986, Huet developed such a French general questionnaire, which
      now also has an English version. Its simplicity is interesting as it could be
      used to survey large populations. The purpose of this study was to assess the
      validity and reliability of this Huet questionnaire in a sample of healthy French
      volunteers. A total of 108 subjects were included in this study, 88 males and 20
      females. The validity of the questionnaire was checked using correlation
      coefficients and a Bland-Altman plot between questionnaire estimations and
      measures of VO2max obtained with a stress test on a cycle ergometer. An
      intraclass correlation coefficient (ICC) was also calculated to determine the
      reliability of the questionnaire. Significant correlation was obtained with the
      Huet questionnaire and measured VO2max (r2 = 0.77, p = 0.0001, SEE = 5.97 ml x kg
      (-1 ) x min- (1), n = 108). The ICC showed very high reliability (ICC= 0.988, n =
      21). The Huet questionnaire is an easy, rapidly administered tool that correlated
      highly with VO2 max in this sample population.

PMID- 15509877
TI  - Treating venous insufficiency with soft silicone dressing.

PMID- 15509878
TI  - When surgical revision is not an option.

PMID- 15509879
TI  - CMS changes policy on OASIS coding for healed stage I and stage II pressure
      ulcers.

PMID- 15509880
TI  - Prevalence of pressure ulcers in Canadian healthcare settings.
AB  - Although statistics regarding the number of pressure ulcers in the US and other
      countries are available, little information is known about the number of
      individuals in Canada who have pressure ulcers. Such information is important to
      assess the scope and healthcare costs of pressure ulcers and develop public
      policies. To obtain estimated pressure ulcer prevalence rates in Canada, existing
      data (gathered between 1990 and 2003) from different healthcare settings across
      the country were obtained from peer-reviewed published studies and from
      unpublished studies provided by individuals and pressure ulcer support surface
      manufacturers. Methods used to gather and report prevalence data in each study
      were critically appraised using a modified version of published criteria.
      Retrospective chart audit studies that did not involve direct patient assessment
      were excluded. The data included information from 18 acute care facilities
      involving 4,831 patients, 23 non-acute care facilities with 3,390 patients, 19
      mixed healthcare settings with 4,200 patients, and five community care agencies
      that surveyed 1,681 patients. Estimates of pressure ulcer prevalence were 25.1%
      (95% Confidence Interval, 23.8% to 26.3%) for acute care settings, 29.9% (95%
      Confidence Interval, 28.3% to 31.4%) in non-acute care settings, 22.1% (95%
      Confidence Interval, 20.9% to 23.4%) in mixed health settings, and 15.1% (95%
      Confidence Interval, 13.4% to 16.8%) in community care. The overall estimate of
      the prevalence of pressure ulcers in all healthcare institutions across Canada
      was 26.0% (95% Confidence Interval, 25.2% to 26.8%). The Canadian prevalence
      estimates differed among the healthcare settings and were higher than those
      reported in the US and the Netherlands. Although additional studies are needed,
      the data suggest that pressure ulcers are a significant concern in all healthcare
      settings in Canada.

PMID- 15509881
TI  - Is bed rest an effective treatment modality for pressure ulcers?
AB  - Despite the well-documented medical, physical, and psychological complications
      associated with this care management option, bed rest remains a frequently
      prescribed treatment modality for conditions such as pressure ulcers. Cognitive
      and psychosocial complications of bed rest include depression, learned
      helplessness, perceptual changes, and fatigue. Physically, complications can
      include contractures, muscle atrophy, osteoporosis, pathologic fractures, urinary
      tract infections, decreased cardiac reserve, decreased stroke volume, resting and
      post-exercise tachycardia, orthostatic hypotension, pulmonary embolism, deep
      venous thrombosis, pneumonia, anorexia, constipation, and bowel impaction.
      Furthermore, the literature does not contain evidence supporting the use of bed
      rest to facilitate healing of pressure ulcers. More suitable approaches to
      pressure ulcer care include limiting bed rest, initiating occupational therapy,
      integrating meaningful tasks into daily activities, increasing outside
      stimulation, involving patients in care decisions and addressing their concerns,
      optimizing nutritional status, and managing pressure and shear throughout daily
      activities. Recommendations for implementing alternatives to bed rest are
      addressed.

PMID- 15509882
TI  - Malnutrition in the institutionalized elderly: the effects on wound healing.
AB  - Under-nutrition and protein-energy malnutrition are seen at alarmingly high rates
      in institutionalized elderly and in patients admitted to hospitals. A combination
      of immobility and loss of lean body mass - which comprises muscle and skin - and
      immune system challenges increases the risk of pressure ulcers by 74%. The
      development of pressure ulcers in the hospital affects 10% of admissions, with
      the elderly at the highest risk. Common causes of malnutrition in the elderly
      involve: decreased appetite, dependency on help for eating, impaired cognition
      and/or communication, poor positioning, frequent acute illnesses with
      gastrointestinal losses, medications that decrease appetite or increase nutrient
      losses, polypharmacy, decreased thirst response, decreased ability to concentrate
      urine, intentional fluid restriction because of fear of incontinence or choking
      if dysphagic, psychosocial factors such as isolation and depression, monotony of
      diet, and higher nutrient density requirements along with the demands of age,
      illness, and disease on the body. All have been found to delay healing and
      increase the risk of pressure ulcer development. In addition, what is ingested
      should contain nutrients to support health and healing. The financial impact of
      malnutrition is high and the consequences for patient morbidity and mortality are
      severe. Practical suggestions to improve the nutritional status of long-term care
      residents include liberalizing previous diet restrictions where safe and
      appropriate, addressing impairments to dentition and swallowing, addressing
      physical and/or cognitive deficits, encouraging family and friends to provide
      favorite foods, auditing/addressing specific food under-consumption, and
      providing prudent nutrient supplementation. Clinicians must be aware of the
      numerous factors in play with regard to nutrition and its impact on not only
      general well-being but also on wound care. Nutritional intervention in pressure
      ulcer management is truly "healing from the inside out."

PMID- 15509883
TI  - Treatment of chronic skin ulcers in individuals with anemia of chronic disease
      using recombinant human erythropoietin (EPO): a review of four cases.
AB  - Patients with hemoglobin greater than or equal to 100 g/L may have difficulty
      healing pressure ulcers because of impaired tissue oxygenation. Decreased
      hemoglobin is often anemia of chronic disease and may be due to the effects of
      inflammatory cytokines on erythroid progenitor cells. Recombinant human
      erythropoietin has been found to reverse anemia of chronic disease and may act as
      a growth factor in wound healing. To review the effect of 6 weeks of subcutaneous
      recombinant human erythropoietin 75 IU/kg administered 3 times weekly to resolve
      refractory anemia of chronic disease and heal Stage IV pressure ulcers, a
      retrospective chart review was conducted of four spinal cord injured patients
      (all men, mean age 59 years +/- 19) with Stage IV pressure ulcers and multiple
      comorbid conditions. The patients received recombinant human erythropoietin
      either through an inpatient spinal cord rehabilitation unit or an outpatient
      wound management clinic as part of interdisciplinary care. Mean hemoglobin
      increased from 88 +/- 7.4 g/L to 110 +/- 3.7 g/L. Mean ulcer surface area
      decreased from 42.3 cm2 (+/- 40.2) to 37.3 cm2 (+/- 44.3) despite extensive
      deroofing of one ulcer and subsequent increase in size. Mean ulcer depth
      decreased from 2.3 cm (+/- 1.2) to 1.2 cm (+/- 1.0). Human recombinant
      erythropoietin shows promise in resolving the refractory anemia of chronic
      disease associated with Stage IV pressure ulcers. Further study is suggested.

PMID- 15509884
TI  - Effects of HA-1077 and Y-27632, two rho-kinase inhibitors, in the human umbilical
      artery.
AB  - A role for the small G protein rho and rho-kinase has been shown in smooth muscle
      contraction regarding Ca++ sensitivity. However, there are no data in the
      literature assessing how this system operates in human umbilical arteries (HUA).
      Therefore, we evaluated the effects of HA-1077 and Y-27632, two rho-kinase
      inhibitors, on agonist-(5-hydroxytryptamine [5-HT]) and depolarization-induced
      (KCl) contractions of HUA. HA-1077 and Y-27632 inhibited 5-HT-induced contractile
      responses at 10-4M concentration but not at 10(-5) M. HA-1077 at 10(-4) M also
      significantly attenuated contractions induced by 20 mM KCl. In addition, HUA
      precontracted with 5-HT relaxed concentration dependently in response to HA-1077
      and Y-27632. When precontracted with KCl, HUA also relaxed dose-dependently in
      response to HA-1077, but the maximal relaxation was significantly smaller than
      the response obtained when precontracted with 5-HT. To determine possible
      involvement of rho-kinase on agonist-induced intracellular calcium-mediated
      contractions, tissues were precontracted with 5-HT in Ca++-free Krebs solution
      before cumulative addition of HA-1077 or Y-27632 (10(-7) to 10(-4) M). Both rho
      kinase inhibitors relaxed HUA completely. Maximum relaxations of HUA to HA-1077
      and Y-27632 were significantly larger than the responses seen in normal Krebs
      solution and were obtained with lower concentrations of the drugs considered to
      be more specific for rho-kinase inhibition. However, preincubation of HUA with HA
      1077 or Y-27632 (10(-5) M for both) did not affect the 5-HT-induced contractions
      in this medium. Finally, immunoblot experiments revealed the expression of rho
      kinase isoform rockII protein in HUA. These results indicate that rhoA/rho-kinase
      pathway can contribute to agonist-induced contractions of HUA. However, this
      effect appears to be limited to intracellular calcium-induced contractions and
      may be more important in sustaining contractions rather than the initial phase of
      force development.

PMID- 15509885
TI  - Visualization of the uptake of individual HDL particles in living cells via the
      scavenger receptor class B type I.
AB  - The scavenger receptor class B type I (SR-BI) plays an important role in
      mediating selective uptake of high-density lipoprotein (HDL)-derived cholesterol
      and cholesteryl ester in liver and steroidogenic tissues. The molecular mechanism
      by which this receptor mediates selective cholesteryl ester uptake remains still
      enigmatic. We applied ultrasensitive fluorescence microscopy to visualize the
      intracellular transport routes of HDL particles taken up via SR-BI in a Chinese
      hamster ovarian cell line. Although diffusion of the receptor bound particles on
      the cell surface is slow, internalization is accompanied by a dramatic increase
      in the mobility of the particles. HDL particles are endocytosed as clusters and
      actively transported to the perinuclear region of the cell. Costaining with
      organelle markers confirmed the involvement of an acidic compartment and the
      Golgi apparatus in the uptake process; finally, resecretion of the HDL particles
      was observed.

PMID- 15509886
TI  - Hydrogenase 3 but not hydrogenase 4 is major in hydrogen gas production by
      Escherichia coli formate hydrogenlyase at acidic pH and in the presence of
      external formate.
AB  - Fermenting Escherichia coli is able to produce formate and molecular hydrogen
      (H2) when grown on glucose. H2 formation is possessed by two hydrogenases, 3 (Hyd
      3) and 4 (Hyd-4), those, in conjunction with formate dehydrogenase H (Fdh-H),
      constitute distinct membrane-associated formate hydrogenylases. At slightly
      alkaline pH (pH 7.5), the production of H2 was found to be dependent on Hyd-4 and
      the F(0)F(1)-adenosine triphosphate (ATPase), whereas external formate increased
      the activity of Hyd-3. In this study with cells grown without and with external
      formate, H2 production dependent on pH was investigated. In both types of cells,
      H2 production was increased after lowering of pH. At acidic pH (pH 5.5), this
      production became insensitive either to N,N'-dicyclohexylcarbodiimide or to
      osmotic shock and it became largely dependent on Fdh-H and Hyd-3 but not Hyd-4
      and the F(0)F(1)-ATPase. The results indicate that Hyd-3 has a major role in H2
      production at acidic pH independently on the F(0)F(1)-ATPase.

PMID- 15509887
TI  - Dependence of the resting [Ca2+]cyt of RBL-1 cells on Ca2+ entry.
AB  - The cytoplasmic Ca2+concentration ([Ca2+]cyt) in resting cells is an equilibrium
      between several influx and efflux mechanisms. Here we address the question of
      whether capacitative Ca2+ entry to some extent is active at resting conditions
      and therefore is part of processes that guarantee a constant [Ca2+]cyt. We
      measured changes of [Ca2+]cyt in RBL-1 cells with fluorometric techniques. An
      increase of the extracellular [Ca2+] from 1.3 mM to 5 mM induced an increase in
      [Ca2+]cyt from 105 +/- 10 nM to 145 +/- 8.5 nM. This increase could be inhibited
      by 10 microM Gd3+, 10 microM La3+ or 50 microM 2-aminoethoxydiphenyl borate,
      blockers of capacitative Ca2+ entry. Application of those blockers to a resting
      cell in a standard extracellular solution (1.3 mM Ca2+) resulted in a decrease of
      [Ca2+]cyt from 105 +/- 10 nM to 88.5 +/- 10 nM with La3+, from 103 +/- 12 to 89
      +/- 12 nM with Gd3+ and from 102 +/- 12 nM to 89.5 +/- 5 nM with 2
      aminoethoxydiphenyl borate. From these data, we conclude that capacitative Ca2+
      entry beside its function in Ca2+ signaling contributes to the regulation of
      resting [Ca2+]cyt.

PMID- 15509888
TI  - Redox status of the eye lens: a regional study.
AB  - The aim of this work was to study the regional variation of some antioxidant
      systems in calf lens. Specific lens regions of nearly same age were obtained by a
      microsectioning technique, and the concentration of reduced and oxidized
      glutathione, protein sulfhydryl groups, and iron were measured in each lens
      region. The concentration of reduced glutathione, the major redox buffer in lens,
      exponentially decreased from the cortical regions to the nucleus. In contrast,
      the concentration of protein sulfhydryl groups gradually increased from the
      cortex toward the nucleus. The protein-bound disulfides remained constant
      throughout the lens. Iron was concentrated in the outer cortical region. The
      results show that the most dynamic redox-active zone in the lens is the
      subcapsular cortical region where the oxidant flux meets a highly reducing
      environment containing a potent redox catalyst.

PMID- 15509889
TI  - Optical techniques for imaging membrane topography.
AB  - In recent years three powerful optical imaging techniques have emerged that
      provide nanometer-scale information about the topography of membrane surfaces,
      whether cellular or artificial: intermembrane fluorescence resonance energy
      transfer (FRET), fluorescence interference contrast microscopy (FLIC), and
      reflection interference contrast microscopy (RICM). In intermembrane FRET, the
      sharp distance dependence of resonant energy transfer between fluorophores allows
      topographic measurements in the Angstrom to few-nanometer range. In FLIC and
      RICM, interference between light from a membrane (either from fluorescent probes,
      or reflected illumination) and light reflected by a planar substrate provide
      spatial sensitivity in the few to hundreds of nanometer range, with few-nanometer
      resolution. All of these techniques are fairly easy to implement. We discuss the
      physics and optics behind each of these tools, as well as practical concerns
      regarding their uses. We also provide examples of their application in imaging
      molecular-scale structures at intermembrane junctions.

PMID- 15509890
TI  - Regulation of tetrahydrobiopterin synthesis and bioavailability in endothelial
      cells.
AB  - Tetrahydrobiopterin (BH4) is a member of the pterin family that has a core
      structure of pyrazino-2,3-d-pyrimidine rings. Because BH4 is an essential
      cofactor for the biosynthesis of nitric oxide (a major vasodilator), there is
      growing interest in BH4 biochemistry in endothelial cells (the cells that line
      blood vessels). BH4 is synthesized via de novo and salvage pathways from
      guanosine 5'-triphosphate (GTP) and 7,8-dihydrobiopterin, respectively, in animal
      cells. GTP cyclohydrolase-I (GTP-CH) is the first and rate-controlling enzyme in
      the de novo pathway. Available evidence shows that endothelial GTP-CH expression
      and BH4 synthesis are stimulated by a wide array of nutritional (phenylalanine
      and arginine), hormonal (insulin and estrogen), immunological (inflammatory
      cytokines including interleukin [IL]-1, interferon-gamma, and tumor necrosis
      factor-alpha), therapeutic (statins and cyclosporin A), and endothelium-derived
      (basic fibroblast growth factor and H2O2) factors. In contrast, glucocorticoids
      and anti-inflammatory cytokines (IL-4, IL-10, and transforming growth factor
      [TGF]-beta) inhibit endothelial BH4 synthesis. Because BH4 is oxidized to 7,8
      dihydrobiopterin and 7,8-dihydropterin at physiological pH, endothelial BH4
      homeostasis is regulated by both BH4 synthesis and its oxidation. Vitamin C,
      folate, and other antioxidants enhance endothelial BH4 bioavailability through
      chemical stabilization or scavenging of reactive oxygen species, thereby
      contributing to the maintenance of physiological homeostasis in the endothelium.
      New knowledge about the cellular and molecular mechanisms for the regulation of
      endothelial BH4 synthesis and bioavailability is beneficial for developing
      effective means to prevent and treat cardiovascular disorders, the leading cause
      of death in developed nations.

PMID- 15509891
TI  - AFM as a high-resolution imaging tool and a molecular bond force probe.
AB  - This focused review summarizes certain aspects of recent developments in the use
      of atomic force microscope in high-resolution imaging of membrane-bound
      biological macromolecules and in molecular force probing of the interaction
      between biological conjugates. We point out the pros and cons in these approaches
      and critically analyze details involved in experiments.

PMID- 15509892
TI  - Protein translocation across the peroxisomal membrane.
AB  - Peroxisomal matrix proteins are synthesized on free cytosolic ribosomes and
      posttranslationally imported into the organelle. Translocation of these newly
      synthesized proteins across the peroxisomal membrane requires the concerted
      action of many different proteins, the majority of which were already identified.
      However, not much is known regarding the mechanism of protein translocation
      across this membrane system. Here, we discuss recent mechanistic and structural
      data. These results point to a model in which proteins en route to the
      peroxisomal matrix are translocated across the organelle membrane by their own
      receptor in a process that occurs through a large membrane protein assembly.

PMID- 15509893
TI  - Reduced glycosaminoglycan sulfation diminishes the agrin signal transduction
      pathway.
AB  - Proteoglycans consist of a protein core complexed to glycosaminoglycan (GAG) side
      chains, are abundant in skeletal muscle cell membranes and basal lamina, and have
      important functions in neuromuscular synapse development. Treatment with chlorate
      results in the undersulfation of heparan sulfate and chondroitin sulfate GAGs in
      cell culture. In addition, chlorate treatment decreases the frequency of
      spontaneous acetylcholine receptor (AChR) clustering in skeletal muscle cell
      culture. AChRs and other molecules cluster to form the postsynaptic component of
      neuromuscular synapses. Chlorate treatment is shown here to decrease the
      frequency of agrin-induced AChR clustering and agrin-induced tyrosine
      phosphorylation of the AChR beta-subunit. These data suggest that reduced GAG
      chain sulfation decreases the frequency of AChR clustering by diminishing the
      agrin signal transduction pathway.

PMID- 15509894
TI  - A fetal risk factor for Parkinson's disease.
AB  - A lack of strong evidence for genetic heritability of idiopathic Parkinson's
      disease (PD) has focused attention on environmental toxicants in the disease
      etiology, particularly agrichemicals. PD is associated with advanced age, but it
      is unclear whether specific neuronal damage could result from insults during
      development. This study hypothesized that prenatal exposure to pesticides would
      disrupt the development of the nigrostriatal dopamine (DA) system and enhance its
      vulnerability to dopaminergic neurotoxicant exposures later in life. Pregnant
      C57BL/6J mice were treated on gestational days 10-17 with saline or the
      pesticides maneb (MB, 1 mg/kg) or paraquat (PQ, 0.3 mg/kg). When offspring were
      evaluated in adulthood, there were no significant effects of prenatal MB or PQ
      exposure on locomotor activity. Subsequently, offspring were treated for 8
      consecutive days with saline, MB (30 mg/kg), or PQ (5 mg/kg). One week after the
      last exposure, only males exposed to prenatal MB and adulthood PQ showed
      significant reductions in locomotor activity (95%) and changes in striatal
      neurochemistry. Stereological assessment of the substantia nigra pars compacta
      (SNpc) and ventral tegmental area correspondingly confirmed selective
      dopaminergic-neuron loss in SNpc. The lack of changes in other exposure groups
      suggests a specificity to the sequence of exposures as well as gender
      specificity. These results suggest that prenatal exposure to MB produces
      selective, permanent alterations of the nigrostriatal dopaminergic system and
      enhances adult susceptibility to PQ exposure. This study implicates a role for
      developmental neurotoxicant exposure in the induction of neurodegenerative
      disorders such as PD.

PMID- 15509895
TI  - Maternal hypoxia during pregnancy delays the development of motor reflexes in
      newborn mice.
AB  - Prenatal hypoxic-ischemic brain injury is believed to cause permanent
      neurological deficits in newborns. We investigated the possibility that maternal
      hypoxia during pregnancy leads to offspring brain damage and its prevention by
      i.p. administration of MgSO4. Pregnant mice at gestation day 17 were exposed to
      hypoxia or air following pretreatment with saline or Mg. Newborn mice to mothers
      exposed to hypoxia demonstrated faster development of morphogenic parameters such
      as eyelid opening, hair growth and teeth eruption. In addition, hypoxia delayed
      the development of motor reflexes. Pretreatment with Mg compensates for hypoxia
      induced impairment and in some cases accelerates the development of these
      functions. In conclusion, maternal hypoxia significantly modifies the
      developmental process of newborn mice. In our study, pretreatment with Mg showed
      significant prophylactic action against motor impairments.

PMID- 15509896
TI  - Microglia in culture: what genes do they express?
AB  - The cell culture model utilized in this study represents one of the most widely
      used paradigms of microglia in vitro. After 14 days, microglia harvested from the
      neonatal rat brain are considered 'mature'. However, it is clear that this
      represents a somewhat arbitrary definition. In this paper, we provide a
      transcriptome definition of such microglial cells. More than 7,000 known genes
      and 1,000 expressed sequence tag clusters were analysed. 'Microglia genes' were
      defined as sequences consistently expressed in all microglia samples tested.
      Accordingly, 388 genes were identified as microglia genes. Another 1,440
      sequences were detected in a subset of the cultures. Genes consistently expressed
      by microglia included genes known to be involved in the cellular immune response,
      brain tissue surveillance, microglial migration as well as proliferation. The
      expression profile reported here provides a baseline against which changes of
      microglia in vitro can be examined. Importantly, expression profiling of normal
      microglia will help to provide the presently purely operational definition of
      'microglial activation' with a molecular biological correlate. Furthermore, the
      data reported here add to our understanding of microglia biology and allow
      projections as to what functions microglia may exert in vivo, as well as in
      vitro.

PMID- 15509897
TI  - Expression of ARVCF in the human ganglionic eminence during fetal development.
AB  - ARVCF (armadillo repeat gene deleted in velocardiofacial syndrome) is a recently
      characterized member of the catenin p120 (ctn) subfamily of the armadillo repeat
      proteins. It is involved in modulation of cell-cell adhesion essential to many
      developmental processes including cellular rearrangement and migration. In the
      present study, by using specific immunohistochemical methods, strongly ARVCF
      immunoreactive cells in a high packing density were found in the human ganglionic
      eminence (GE), a telencephalic structure which gives rise to precursor neurons of
      the striatum, the amygdala and the basal nucleus of Meynert. From 20 to 25 weeks
      of gestation, stripes of immunoreactive cells were found to extend from both the
      superior part of the GE towards the intermediate zone of the neocortex and from
      the inferior part of the GE either towards the amygdaloid complex or more
      laterally towards the intermediate zone. Bands of ARVCF-positive cells were also
      identified in the gangliothalamic body, a transient target for the migrating
      neurons from the GE to the thalamus. Double immunolabelling with ARVCF and
      calretinin antibodies, which mark the GE neurons migrating towards the cerebral
      cortex, revealed that a majority of ARVCF-positive neurons at the periphery of
      the GE and the cellular extensions from the GE also expressed calretinin. Our
      results implicate a very close association of ARVCF with migrating neurons from
      the GE.

PMID- 15509898
TI  - Prenatal cannabinoid exposure down- regulates glutamate transporter expressions
      (GLAST and EAAC1) in the rat cerebellum.
AB  - Efficient reuptake of synaptically released glutamate is essential for preventing
      glutamate receptor overstimulation and neuronal death. Glutamate transporters
      play a vital role in removing extracellular glutamate from the synaptic cleft.
      This study analyzed the expression of the glial (GLAST) and neuronal (EAAC1)
      subtypes of glutamate transporter in the cerebellum of male and female offspring
      exposed pre- and postnatally to Delta9-tetrahydrocannabinol (THC, the main
      component of marijuana). Pregnant rats were administered saline or THC from
      gestational day 5 to postnatal day 20 (PD20). The expression of glutamate
      transporters was examined at PD20, PD30 and PD70 (10 and 50 days after THC
      withdrawal) to analyze the short- and long-term effects of prenatal THC exposure.
      The expression of the glutamate transporter GLAST in astroglial cells and EAAC1
      in Purkinje neurons decreased in THC-exposed offspring compared to controls. This
      reduction was observed at all ages but mainly in males. Moreover, the glial
      glutamate transporter level in THC-exposed rats (quantified by Western blot) was
      lower than in control rats. These results suggest that THC exposure during
      cerebellar development may alter the glutamatergic system not only during the
      period of drug exposure but in the postnatal stage following withdrawal. The down
      regulation reported here might reflect an abnormal maturation of the
      glutamatergic neuron-glia circuitry.

PMID- 15509899
TI  - Perinatal androgenization prevents age-related neuron loss in the sexually
      dimorphic nucleus of the preoptic area in female rats.
AB  - To investigate the effect of perinatal testosterone exposure, which simulates the
      endogenous testosterone peak, on neuron loss during aging, nuclear morphology was
      evaluated in male and female rats as well as in female rats treated with
      testosterone perinatally followed by ovariectomy (TE/Ovx). Additionally, neuronal
      apoptosis, which occurred primarily at postnatal day 8 (PND8), was identified by
      in situ TUNEL staining. Neuronal density, nuclear volume, total neuronal number
      and pyknotic ratio were estimated after HE stain at PND8, middle age and old age.
      The results showed that age-related decrease in neuronal nuclear volume and total
      neuron number in the sexually dimorphic nucleus of the preoptic area (SDN-POA) of
      female rats was significantly diminished by TE/Ovx. The pyknotic ratio in the SDN
      POA of female rats at PND8 was significantly higher than that of males, and
      neuronal death was reversed by testosterone exposure, while no significant
      difference of pyknotic ratios was observed among male, female and TE/Ovx female
      rats at both middle and old age. Moreover, the high apoptotic incidence of female
      rats at PND8 was significantly diminished by testosterone exposure. These results
      suggest that neuron loss in the SDN-POA during aging may be predominantly
      determined by perinatal testosterone through modulation of postnatal neuronal
      apoptosis.

PMID- 15509900
TI  - The role of glucose in brain injury following the combination of
      lipopolysaccharide or lipoteichoic acid and hypoxia-ischemia in neonatal rats.
AB  - We have previously shown that lipopolysaccharide (LPS) sensitizes the immature
      rat brain to subsequent hypoxic-ischemic (HI) injury; however, the underlying
      mechanisms remain unclear. In this study, we examined the role of glucose in the
      sensitizing effects of LPS and lipoteichoic acid (LTA) in combination with HI in
      7-day-old rats. LPS/HI resulted in hypoglycemia which lasted 24 h and lactate
      levels were increased from 6 to 10 h after LPS administration. LPS/HI induced
      severe brain injury, which persisted 2 weeks after LPS/HI. Administration of
      glucose to LPS-treated animals with HI reduced brain injury in the cerebral
      cortex and hippocampus, while striatal damage remained. LTA/HI did not affect
      blood glucose, lactate or brain injury. In conclusion, enhanced blood glucose
      levels during HI after LPS administration conferred protection in some brain
      regions but not in the striatum, suggesting that alterations in glucose can only
      partly explain the sensitizing effect of LPS.

PMID- 15509901
TI  - Isolation of cystatin C via functional cloning of astrocyte differentiation
      factors.
AB  - We screened for factors upregulating glial fibrillary acidic protein (GFAP)
      promoter activity by functional cloning with an immature astrocyte cell line
      (HB108-10) harboring a GFAP-lacZ construct. One cDNA clone that repeatedly
      upregulated lacZ expression encoded cystatin C (CysC), a cysteine protease
      inhibitor. TGF-beta induced CysC and GFAP expression in AP-16 cells, an astrocyte
      progenitor-like cell line expressing GLAST (a glutamate transporter subtype
      specifically expressed in immature astrocytes). CysC gene expression started
      earlier than that of GFAP in the mouse forebrain. It started in the ventricular
      zone at a similar period as (or slightly after) GLAST expression, but before GFAP
      expression. Although previous data showed that CysC is involved in the
      maintenance of adult neural stem cells, our data indicate that it is involved in
      astrocyte differentiation during mouse brain development.

PMID- 15509902
TI  - CC-chemokine RANTES is increased in serum and urine in the early post
      transplantation period of human renal allograft recipients.
AB  - BACKGROUND: The chemokine RANTES is a potent chemoattractant for T cells and
      monocytes that has been shown to enhance inflammation. The aim of our study was
      to investigate whether RANTES is upregulated within the early post
      transplantation period that may influence short-time allograft function rate.
      METHODS: Serum and urine samples from transplanted renal allograft recipients (n
      = 17) were obtained from specimens taken for diagnostic reasons. Four patients
      developed biopsy-proven rejection episodes within the first month. Time course of
      RANTES was studied within the first 12 days after renal transplantation using
      ELISA technique. Data were tested for significances between patients with
      rejection and without rejection, compared to healthy volunteers as controls, and
      correlated with clinical data. RESULTS: In the control group RANTES concentration
      was 37.2 +/- 2.7 ng/ml (serum) and 8.1 +/- 1.3 pg/ml (urine), respectively. In
      transplanted recipients serum RANTES was significantly upregulated up to 132 +/-
      28 ng/ml on day 1 after transplantation and remained elevated within the first 12
      days (n = 17). Time course of urine RANTES demonstrated elevated concentrations
      with 754 +/- 115 pg/ml on day 1 followed by an continuous decrease to 22.3 +/- 7
      pg/ml on day 12 (n = 17). No significant differences could be detected between
      patients with rejection and without rejection episodes. CONCLUSIONS: In contrast
      to data of other urinary marker molecules (like IL-6), there are no significant
      differences between the rejection and non-rejection group. RANTES is therefore
      not suitable for early detection of rejection. Nevertheless, serum and urine
      RANTES concentrations were highly elevated in freshly transplanted renal
      allograft recipients reflecting an activated immune system.

PMID- 15509903
TI  - Immunologic and osteogeneic properties of xenogeneic and allogeneic demineralized
      bone transplants.
AB  - Xenografting is increasingly being developed as a response to the shortage of
      human tissues. However, antigenic components of bone material eliciting immune
      responses--particularly of cellular nature--are blamed for the reduction of the
      osteoinductive properties of bone and bone-derived implants. The aim of our study
      was to compare the immunologic response and osteogenesis induced by antigen
      depleted allogeneic and xenogeneic bone-derived implants to that induced by
      partially antigen-depleted material heterotopically placed (muscular pouch) in
      rats. Wistar rats received bone-derived implants of different antigeneic
      condition, from both xenogeneic (rabbit) and allogeneic (rat) origin. After
      sacrifice, animals were evaluated for osteogenesis and immune response. New bone
      formation was observed around all bone-derived implants, whether fully or
      partially antigen-extracted, and from both xenogeneic and allogeneic origin. No
      significant humoral response resulted following bone implantation. Cellular
      response showed a similar pattern in partial and fully antigen-extracted bone of
      both allogeneic and xenogeneic origin. Xenogeneic antigen-extracted bone from
      safe donor sources could be a suitable solution to human tissue shortage in a
      near future.

PMID- 15509904
TI  - Effects of a peracetic acid disinfection protocol on the biocompatibility and
      biomechanical properties of human patellar tendon allografts.
AB  - Patellar tendon allografts, retrieved from cadaveric human donors, are widely
      used for replacement of damaged cruciate ligaments. In common with other tissue
      allografts originating from cadaveric donors, there are concerns regarding the
      potential for disease transmission from the donor to the recipient. Additionally,
      retrieval and subsequent processing protocols expose the graft to the risk of
      environmental contamination. For these reasons, disinfection or sterilisation
      protocols are necessary for these grafts before they are used clinically. A high
      level disinfection protocol, utilising peracetic acid (PAA), has been developed
      and investigated for its effects on the biocompatibility and biomechanics of the
      patellar tendon allografts. PAA disinfection did not render the grafts either
      cytotoxic or liable to provoke an inflammatory response as assessed in vitro .
      However, the protocol was shown to increase the size of gaps between the tendon
      fibres in the matrix and render the grafts more susceptible to digestion with
      collagenase. Biomechanical studies of the tendons showed that PAA treatment had
      no effect on the ultimate tensile stress or Young's modulus of the tendons, and
      that ultimate strain was significantly higher in PAA treated tendons.

PMID- 15509905
TI  - Ophthalmic applications of preserved human amniotic membrane: a review of current
      indications.
AB  - Preserved human amniotic membrane (AM) is currently being used for a wide
      spectrum of ocular surface disorders. The AM has a basement membrane, which
      promotes epithelial cell migration and adhesion. The presence of a unique
      avascular stromal matrix reduces inflammation, neovascularization and fibrosis.
      The basic tenets of amniotic membrane transplantation (AMT) are to promote re
      epithelialization, to reconstruct the ocular surface and to provide symptomatic
      relief from surface aberrations. AMT is a useful technique for reconstruction of
      surface defects resulting from removal of surface tumors and symblephara. AMT has
      effectively restored a stable corneal epithelium in eyes with, persistent
      epithelial defects and corneal ulcers. In the setting of acute ocular burns and
      SJS, AMT has satisfactorily reduced scarring and inflammation. AMT alone may be
      an effective alternative for partial limbal stem cell deficiency. However
      remarkable improvements in surface stability have resulted from concurrent AMT
      and limbal stem cell transplantation, wherein the limbal grafts are obtained from
      the normal fellow eye, living relative or cadaveric eye. In severe or bilateral
      cases, well being of the donor eye is a major concern. Currently, the most unique
      application of preserved human AM in ophthalmology is its use as a substrate for
      ex-vivo expansion of corneal and conjunctival epithelium. In this novel technique
      of tissue engineering, epithelial stem cells can be safely harvested and expanded
      on denuded AM. The resultant composite cultured tissue has been successfully
      transplanted to restore vision, as well as the structure and function of damaged
      ocular surfaces.

PMID- 15509906
TI  - From Langerhans islets to pancreas transplantation over the past 30 years: a
      review with personal contributions.
AB  - Organ, tissue and cell banking is currently an important method used to prevent
      death of cells in replacement transplantation therapy. From 1975 to 1985 the
      author performed experimental transplantations of islets isolated by collagenase
      digestion through injection into the liver through the portal vein, or by
      transplantation of minced neonatal pancreases under the renal capsule of alloxan
      or spreptozotocin into severely chronic diabetic rats and mice. Seventy of the
      256 transplanted rats and mice were cured for 1 year, i.e. one-third of their
      life span, at the 3rd to 15th inbreeding and only 2 weeks of immunosuppression by
      azathioprine or cyclosporin A. The author compares his results with those
      achieved later with diabetic patients by whole pancreas transplantation,
      including prevention of diabetic renal and ocular complications, infertility,
      health of progeny of cured rats, and slow rejection and possibility of cure by
      repeated transplantation. He welcomes the return to islet transplantation, and
      possibly also of immunologically tolerant pancreatic stem cell transplantation,
      or transplantation of subcutaneous fibroblasts, transfected with a complex
      insulin gene, which will produce adequate insulin to prevent hyperglycemia, as
      does hepatic pyruvate kinase from an insulin analog, a therapy that will not need
      permanent immunosuppression.

PMID- 15509907
TI  - Establishment of the 1st European Tissue Bank and a vision of the future of
      tissue banking.
AB  - The paper offers a short history of the oldest European tissue bank, in
      cooperation with important international organizations and eduction authorities.
      The final part details the organization of development in research and clinical
      use by the bank in the field of human embryonal cells.

PMID- 15509908
TI  - European Association of Tissue Banks Honorary Membership Award to Dr. Rudiger von
      Versen, MD, DMSc.

PMID- 15509912
TI  - Combining EEG and FMRI in epilepsy: methodological challenges and clinical
      results.
AB  - It is now possible to combine continuous recording of the EEG and continuous
      functional MRI scanning. This makes it possible to determine the regions of the
      brain showing changes in the fMRI signal in response to epileptic spikes
      occurring in the EEG. This article reviews the experience with this method in
      more than 100 studies performed over the last 4 years at the Montreal
      Neurological Institute. The technique is complex, and the authors review the
      various issues related to obtaining a good-quality EEG in the hostile environment
      of the magnetic resonance scanner, the statistical analysis of magnetic resonance
      images, in particular the issue of knowing what is the hemodynamic response
      function appropriate for the analysis of epileptic spikes, and the combination of
      EEG and fMRI results. The difficult theoretical issues raised by the
      interpretation of activation and deactivation, both frequently seen in response
      to spikes, are discussed. Finally, the authors give examples of fMRI responses
      seen with focal spikes and with generalized spike and wave discharges.

PMID- 15509913
TI  - EEG/functional MRI in epilepsy: The Queen Square Experience.
AB  - The recording of EEG during functional MRI scanning (EEG/fMRI) has opened up new
      dimensions in brain research. The simultaneous recording of EEG activity and its
      temparospatial haemodynamic correlates is a powerful tool in the non-invasive
      mapping of normal and pathological brain function. The technological constraints
      imposed by having a conductor (the EEG) within the magnetic environment of the
      MRI scanner have been sufficiently overcome for high quality EEG recording during
      MRI. The initial applications of EEG/fMRI were in the study of epileptiform
      discharges in epilepsy. This has been rapidly followed by studies of normal EEG
      rhythms and evoked response in healthy subjects. The ability to map brain areas
      involved in the generation of epileptiform discharges recorded on the surface EEG
      has been shown using EEG/fMRI in patients with epilepsy. This has potential
      clinical applications in providing additional localizing information in the pre
      surgical workup of epilepsy patients and in gaining a greater understanding of
      the neurobiology of interictal epileptiform discharges and epileptic seizures. In
      this review we address the issues in recording EEG during fMRI and review the
      application of EEG/fMRI in the study of patients with epilepsy at our centre.

PMID- 15509914
TI  - Electroencephalographic and epileptic patterns in X chromosome anomalies.
AB  - Although epilepsy and mental retardation are commonly observed in individuals
      with chromosomal aberrations, the identification of EEG/epileptic profiles in
      those with specific chromosome anomalies remains difficult. A few syndromes seem
      to show peculiar clinical and EEG associations. The authors report an
      electroclinical investigation on a group of patients carrying X chromosome
      anomalies: 16 patients with Turner's syndrome, 17 with Klinefelter's syndrome, 1
      with an X-autosomal rearrangement, 2 with Xq isochromosome [Xq(i)], and 7 with
      triple X syndrome. Epilepsy and/or EEG anomalies were found in three of the
      patients with Klinefelter's syndrome, in one patient with an X-autosomal
      rearrangement, and in five of those with triple X syndrome. No epilepsy or EEG
      anomalies were detected in the other patients. Epilepsy may be associated with
      Klinefelter's syndrome. In addition, the authors found that an electroclinical
      pattern, represented by paroxysmal activity in the posterior regions (temporo
      parieto-occipital areas) with complex partial seizures and easily controlled by
      antiepileptic drugs, may be present in patients with triple X syndrome. In
      contrast, gross X-autosomal rearrangements are associated with polymorphic
      EEG/epileptic findings. Although further studies are needed to validate these
      observations, they clearly confirm the strict relationship between X chromosome
      anomalies and epilepsy.

PMID- 15509915
TI  - Dipole density of low-frequency and spike magnetic activity: a reliable procedure
      in presurgical evaluation of temporal lobe epilepsy.
AB  - Conventional visual analysis and dipole density analysis of
      magnetoencephalographic data for both spike and low-frequency magnetic activity
      were compared for presurgical evaluation in temporal lobe epilepsy (TLE) in a
      sample of 26 drug-resistant operated TLE patients. A series of logistic
      regression analyses were performed. Dipole density sensitivity was superior to
      visual localization analysis. Three separated logistic models were calculated for
      interictal spikes, low-frequency magnetic activity, and the combination of both
      measures. A combined interictal spike/low-frequency magnetic activity model
      predicted correctly the operated temporal lobe in all patients. Clear-cut
      criteria for the probability model are proposed that are valid for 92.3% of cases
      in the sample. The quantitative approach proposed by this study is an evidence
      based model for presurgical evaluation of temporal lobe epilepsy, which improves
      previous magnetoencephalographic investigations and establishes working clinical
      criteria for patient evaluation in TLE.

PMID- 15509916
TI  - Electric source imaging in temporal lobe epilepsy.
AB  - The objective of this study was to determine the validity of interictal spike
      (IIS) source localization in temporal lobe epilepsies (TLE) using
      stereoelectroencephalography as a validating method. Twenty patients with drug
      resistant TLE were studied with high-resolution EEG and
      stereoelectroencephalography. Sixty-four scalp channels, a realistic head model,
      and different algorithms were used. For each patient, the intracerebral
      interictal distribution was studied and classified into one of three groups: L
      (mainly lateral), ML (mediolateral), and M (medial). In group L (three patients),
      surface IIS were recorded with a high signal-to-noise ratio. Source localizations
      designated all or part of the intracerebral interictal distribution. In group ML
      (11 patients), 8 patients had surface IIS, only 5 of which were localizable. High
      resolution EEG permitted localization of the more lateral portion and definition
      of its rostrocaudal extension. A common pattern was identified in three patients
      with a predominant role of the temporal pole. In group M (six patients), four
      patients had rare surface IIS, none of which were localizable. Surface EEG does
      not record IIS limited to medial temporal lobe structures. In TLE with a
      mediolateral or a lateral interictal distribution, only the lateral component is
      detectable on surface EEG and accurately localizable by source localization
      tools.

PMID- 15509917
TI  - Vagus nerve stimulation for refractory epilepsy: a transatlantic experience.
AB  - Vagus nerve stimulation (VNS) is an alternative treatment for medically or
      surgically refractory epilepsy. The long-term efficacy and safety of VNS were
      evaluated in a large patient series at Ghent University Hospital and Dartmouth
      Hitchcock Medical Center. Between March 1995 and February 2003, seizure frequency
      and type as well as prescribed antiepileptic drugs and side effects were
      prospectively assessed in 131 patients treated with VNS in either center.
      Patients with a minimum follow-up duration of 6 months were included in the
      efficacy and safety analysis. A total of 118 of 131 implanted patients had a
      minimum postimplantation follow-up period of 6 months (mean, 33 months). The mean
      age of these patients was 32 years and the mean duration of refractory epilepsy
      was 22 years. The mean reduction in monthly seizure frequency in all patients was
      55% (range, 0-100; SD = 31.6). Seven percent of patients were free of seizures
      with impaired consciousness, 50% of patients had a seizure frequency reduction of
      more than 50%, and 21% of patients were nonresponders. Fifteen patients reported
      stimulation-related side effects such as hoarseness or gagging. In a large
      patient series from two geographically distinct epilepsy centers located in two
      different continents, VNS proved to be efficacious and safe during long-term
      follow-up.

PMID- 15509918
TI  - Ontogeny of arousal.
AB  - Ontogeny of arousal data constitute a vital supplement to the sparse literature
      on spontaneous neuronal activity. These data demonstrate that measurable infant
      spontaneous arousals (SAs) with an inherent oscillatory entrainment occur six
      times more in active sleep than in quiet sleep of the same duration and are
      identifiable as a human neurobiologic function. These SAs are not significantly
      associated with race or ethnicity, gender, total hours spent sleeping, percent
      time spent in active or quiet sleep, preterm status, history of a life
      threatening event, having had a sibling who died of sudden infant death syndrome
      (SIDS), or having had a mother who smoked during this pregnancy. As measurable
      neurophysiologic events, SAs establish parameters for research at molecular and
      molar levels focusing on several critical areas: (1) the neuronal control of SA
      related to neurotransmitters, (2) as a significant antecedent factor in clinical
      cardiorespiratory events occurring in infants at high epidemiologic risk for
      SIDS; (3) as a regulatory biologic factor underlying temperament and executive
      cognitive functioning, and (4) morbidity and mortality effects possibly related
      to therapeutic interventions that alter SA levels.

PMID- 15509919
TI  - Mind, brain, body, and soul: a review of the electrophysiological undercurrents
      for Dr. Frankenstein.
AB  - Mary Shelley's Frankenstein is perhaps the most famous work of medical science
      fiction. She and her husband, the poet Percy Shelley, were aware of nascent
      neuroscience experimentation and the effects of electricity on neuromuscular
      function. Such experiments generated theories of voluntary, involuntary, and
      unconscious neuromuscular function; animal electricity; and the anima--the human
      vital principle. In Germany and Italy, investigators were performing bizarre
      electrical experiments on animals and humans to "reanimate" lifeless limbs and
      bodies. These demonstrations and theories find expression in Frankenstein and
      provide models for Dr. Frankenstein and his creation.

PMID- 15509920
TI  - Squamous cell carcinoma of the skin.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Identify the subtypes of squamous cell carcinoma of the skin. 2. Identify
      factors that affect recurrence and/or metastasis. 3. Develop a surgical
      management plan for treating high-risk squamous cell carcinoma of the skin. In
      treating squamous cell carcinoma of the skin, a key concept in proper management
      is understanding why certain tumors are more prone to both recurrence and
      metastasis. When developing a surgical management plan, an understanding of "high
      risk" is essential. This article concentrates on identifying those tumor subtypes
      and factors that may serve as predictors of high-risk status as well as on
      providing management suggestions.

PMID- 15509921
TI  - Accuracy in identification of patients with 22q11.2 deletion by likely care
      providers using facial photographs.
AB  - Numerous facial characteristics are associated with velocardiofacial syndrome.
      Care providers may use these facial characteristics to identify patients who may
      benefit from fluorescence in situ hybridization genetic testing to determine the
      presence of the 22q11.2 deletion. The purpose of this study was to test the
      hypothesis that experienced care providers were able to correctly diagnose the
      22q11.2 deletion on the basis of studying frontal facial photographs. After
      approval was obtained from the human studies committee, patients who had
      undergone fluorescence in situ hybridization genetics testing for the presence of
      a 22q11.2 deletion were asked to submit two frontal photographs: one at infancy
      and one beyond the second birthday. These photographs were randomized, made
      anonymous, and then placed on a secure Web site. Specialists in the fields of
      plastic surgery, otolaryngology, genetics, and speech pathology were asked to
      evaluate their experience and confidence levels in diagnosing a 22q11.2 deletion
      and were then asked to rate the photographs by likelihood of deletion using a
      five-point Likert scale. Thirty-two specialists (10 surgeons, nine geneticists,
      and 13 speech pathologists) participated in the study. On the basis of clear
      responses, respondents predicted the presence (sensitivity) and absence
      (specificity) of the 22q11.2 deletion at chance levels. Of the remaining
      responses, 20 to 25 percent were unsure and 20 to 25 percent were clearly wrong.
      When an unsure response was treated as a weak positive, the results favored
      sensitivity slightly, with a sensitivity of 70 percent and a specificity of 50
      percent. Sensitivity improved somewhat with experience, as measured by the number
      of patients seen per year. The prediction of the presence or absence of the
      22q11.2 deletion at chance levels suggests that the ability to diagnose on the
      basis of appearance alone is not a sufficient diagnostic tool. Although the
      ability does increase with experience, it is of statistical but not clinical
      significance.

PMID- 15509922
TI  - Primary correction of unilateral cleft lip nasal deformity in Asian patients:
      anthropometric evaluation.
AB  - Previously it was thought that primary correction of nasal deformity in cleft lip
      patients would cause developmental impairment of the nose. It is now widely
      accepted that simultaneous correction of the cleft lip nasal deformity has no
      adverse effect on nasal growth. Thus, the authors tried to evaluate the results
      of primary correction of cleft lip in Asian patients. Of 412 cases of cleft lip,
      195 cases were corrected by means of the conventional method from June of 1992 to
      June of 1997, and 217 cases were corrected by simultaneous rhinoplasty from July
      of 1997 to October of 2001. The average patient age was 3 months. Photographs and
      anthropometric evaluation were used to evaluate the results. Nasal tip
      projection, columellar length, and nasal width were measured in 60 randomized
      normal children, 30 randomized children treated with the conventional method, and
      30 randomized children with primary nasal repair. Data were analyzed using t
      tests, and the level of significance was 5 percent (p < 0.05). In cases of
      simultaneous repair, nasal tip projection and columellar length were increased
      24.8 percent and 28.8 percent, respectively. Nasal width was increased 12.3
      percent in the cases of simultaneous repair and 12.6 percent in the cases without
      primary rhinoplasty. Simultaneous repair of cleft lip and nasal deformity in
      Asian patients showed that more symmetry of nostril and nasal dome projection and
      better correction of buckling and alar flaring were achieved. More balanced
      growth and development of the alar complex was achieved, and no interference with
      nasal growth was encountered.

PMID- 15509923
TI  - Long-term skeletal stability after maxillary advancement with distraction
      osteogenesis using a rigid external distraction device in cleft maxillary
      deformities.
AB  - Rigid external distraction is a highly effective technique for correction of
      maxillary hypoplasia in patients with orofacial clefts. The clinical results
      after correction of sagittal maxillary deformities in both the adult and
      pediatric age groups have been stable. The purpose of this retrospective
      longitudinal cephalometric study was to review the long-term stability of the
      repositioned maxilla in cleft patients who underwent maxillary advancement with
      rigid external distraction. Between April 1, 1995, and April 1, 1999, 17
      consecutive patients with cleft maxillary hypoplasia underwent maxillary
      advancement using rigid external distraction. There were 13 male patients and
      four female patients, with ages ranging from 5.2 to 23.6 years (mean, 12.6
      years). After a modified complete high Le Fort I osteotomy and a latency period
      of 3 to 5 days, patients underwent maxillary advancement with rigid external
      distraction until proper facial convexity and dental overjet and overbite were
      obtained. After active distraction, a 3- to 4-week period of rigid retention was
      undertaken; this was followed by removable elastic retention for 6 to 8 weeks
      using, during sleep time, an orthodontic protraction face mask. Cephalometric
      radiographs were obtained preoperatively, after distraction, at 1 year after
      distraction, and 2 or more years after distraction. The mean follow-up was 3.3
      years (minimum, 2.1 years; maximum, 5.3 years). The following measurements were
      obtained in each cephalogram: three linear horizontal and two linear vertical
      maxillary measurements, two angular craniomaxillary measurements, and one
      craniomandibular measurement. Differences between the preoperative and
      postoperative cephalometric values were analyzed by paired t tests (p < 0.05).
      The cephalometric analysis demonstrated postoperatively significant advancement
      of the maxilla. In addition, the mandibular plane angle opened 1.2 degrees after
      surgery. After the 1- to 3-year follow-up period, the maxilla was stable in the
      sagittal plane. Minimal anteroposterior growth was observed in the maxilla
      compared with that exhibited in the anterior cranial base. However, there was
      significant vertical maxillary growth over the 3-year observation period. The
      mandibular plane angle tended to decrease during the follow-up period. The
      cephalometric data from this study support the clinical impression of maxillary
      stability after maxillary advancement with rigid external distraction in cleft
      patients. This effective and stable technique is now considered for all pediatric
      patients with severe cleft maxillary hypoplasia and for adolescent and adult
      patients with moderate to severe deformities.

PMID- 15509925
TI  - Treatment of midfacial defects using prostheses supported by ITI dental implants.
AB  - The purpose of this study was to evaluate retrospectively the use of ITI dental
      implants used for anchoring facial prostheses in the restorative treatment of
      midface defects. The authors analyzed the clinical data of 26 patients with
      orbital defects (n = 11), orbitonasal defects (n = 4), orbitonasomaxillary
      defects (n = 3), and nasal defects (n = 8). Data included age, sex, primary
      disease, implant position, implant length, implant failure, prosthetic
      attachment, radiation therapy, and peri-implant skin reactions. Follow-up was at
      1, 3, 6, and 12 months and then on a yearly basis. The authors noted the status
      of healing and complications, if any. In total, 62 implants were placed as
      follows: 27 (43.5 percent) for orbital prostheses, 12 (19.4 percent) for
      orbitonasal prostheses, 14 (22.6 percent) for orbitonasomaxillary prostheses, and
      nine (14.5 percent) for nasal prostheses. Thirty-eight implants (61.3 percent)
      were placed in previously irradiated areas in 18 patients (69.2 percent). Mild
      skin reactions together with mild accumulation of sebaceous crusting around
      implants were recorded in 14.2 percent of the skin observations. No patient
      experienced severe inflammation requiring administration of systemic antibiotics
      or surgical revision. Implant success was 100 percent in both irradiated and
      nonirradiated patients. In conclusion, ITI dental implants result in a high rate
      of success in retaining midface prostheses and offer good stability and aesthetic
      satisfaction.

PMID- 15509926
TI  - Nasal reconstruction--beyond aesthetic subunits: a 15-year review of 1334 cases.
AB  - A retrospective analysis was performed on 1334 patients who underwent nasal
      reconstruction between 1986 and 2001. The senior author performed all
      reconstructions in this series after Mohs' histographic excisions. Only secondary
      reconstructions were performed without a preceding Mohs' excision. Methods of
      reconstruction, number of operations per patient, locations of defects, and
      complications were recorded. Using preoperative and postoperative photographs,
      aesthetic results were reviewed. Basal cell carcinoma was the most common lesion,
      followed by squamous cancer and melanoma. The average age of the patients was 51
      years. Cancers most commonly arose on the dorsum, ala, and tip. Of 1334 cases, a
      1.9 percent recurrence rate was documented. The average time between surgery and
      clinical recognition of recurrence was 39 months. All recurrent lesions were
      reexcised by the Mohs' technique. Eighty-one percent of reconstructions were
      completed in three or fewer stages. Seventy-five percent of reconstructions were
      completed in two stages. Primary dermabrasion or primary laserbrasion using
      carbon dioxide or erbium lasers was used in nearly every case. Early secondary
      dermabrasion or laserbrasion was used in a few cases where indicated. A 1.2
      percent revision rate was noted (16 patients). Thirteen partial flap necroses
      required revision. Three patients experienced dehiscence at the donor site of
      paramedian forehead flaps. A preferred philosophy toward nasal reconstruction is
      described. The goal is to achieve optimal cosmetic and functional results while
      minimizing stages and resection of healthy tissue. Six core principles are
      advocated that guide efficient and successful nasal reconstruction: (1) maximal
      conservation of native tissue is advised; (2) reconstruction of the defect, not
      the subunit, is advised; (3) complementary ablative procedures, such as primary
      dermabrasion, enhance the final result and decrease the number of revisionary
      procedures; (4) primary defatting also decreases the number of revisionary
      procedures; (5) when possible, the use of axial pattern flaps is preferred; and
      (6) good contour is the aesthetic endpoint.

PMID- 15509928
TI  - Cicatricial eyebrow reconstruction with a dense-packing one- to two-hair grafting
      technique.
AB  - Scarring eyebrow loss is usually repaired with a hair-bearing island scalp flap
      or scalp strip grafting technique. The results, however, are usually not
      desirable with regard to appearance. In this article, a one- or two-hair graft
      with a dense-packing technique was developed for cicatricial eyebrow
      reconstruction. It was carried out by harvesting a scalp strip close to the
      hairline of the back, then dividing it into a series of one- or two-hair grafts,
      and finally implanting the grafts into the prepared recipient holes of the
      eyebrow with a desired hair direction. With the authors' experience in treating
      96 patients (154 eyebrows) in cases of burn, skin grafting, traumatic scarring,
      and chemical peeling scar after tattoo removal, the eyebrows could be restored in
      only one session. In general, 150 to 200 grafts with 200 to 250 hairs were needed
      for a complete male eyebrow reconstruction and 100 to 150 grafts with 150 to 200
      hairs were needed for a complete female eyebrow reconstruction. The maximal hair
      density was 91.5 hairs/cm per session. Over a 6-month follow-up period, the mean
      graft survival rate reached 98.1 percent. All of the patients achieved
      satisfactory results, with a very natural appearance. These results indicate that
      the above-mentioned technique could be a practical, effective, and probably ideal
      method for cicatricial eyebrow reconstruction.

PMID- 15509929
TI  - Leave the fat, skip the bolster: thinking outside the box in lower third nasal
      reconstruction.
AB  - Defects of the lower third of the nose often present especially challenging
      reconstructive dilemmas. The surrounding skin to match is often thick, sebaceous,
      and sun damaged, none of which characterizes the historically ideal periauricular
      donor skin for grafting. The surrounding nasal skin is quite stiff, precluding
      very small local flaps. To avoid the "misplaced patch" appearance of most classic
      full-thickness grafts to this area or the depressed scar of an elliptical
      excision, many surgeons turn to larger local or regional flaps. These provide not
      only skin color and texture match but also the necessary several millimeters of
      subcutaneous fat necessary for proper tip aesthetics. Many defects of the lower
      third are small, making many surgeons reluctant to employ these larger flaps with
      their long scars and potential to twist or distort delicate tip or ala anatomy.
      The author has sought a means to transport skin and subcutaneous fat for lower
      third nasal defects outside of flaps. On the basis of the superiority of
      nasolabial fold scars and a vast positive experience in the literature utilizing
      skin and fat composite grafts with no bolsters, the author applied these
      techniques to 33 lower third nasal defects in 29 patients. Of 33 grafts varying
      in size from 4 mm circular to 17 mm x 16 mm and retaining 1 to 5 mm of fat, no
      grafts were lost. Four grafts developed a 30 percent area or less of central
      necrosis resulting in localized depression. Three of these four grafts were in
      active smokers and the fourth graft was in a former smoker. Aside from these four
      grafts and one with considerable excess fat early in the series, contour was good
      to excellent. Hypopigmentation is still common but improves with time. Easily
      performed composite grafts effectively carry the necessary fat for aesthetic
      reconstruction and do not risk long scars on the nose and twisting of the tip and
      ala that can result from flaps. Revisions are infrequent and extremely simple
      when indicated.

PMID- 15509930
TI  - Modified mattress suture technique to correct anterior septal deviation.
AB  - The purpose of this study was to evaluate the efficacy of a modified mattress
      suture technique in septal anterior deviation correction and to compare it with
      the Hinderer technique. This was a randomized, controlled, single-blind clinical
      trial. Fifty patients with anterior septal deviation were assigned to one of two
      surgery treatment groups: in group A, 25 patients underwent anterior septoplasty
      with modified mattress suture technique; and in group B, 25 patients underwent
      anterior septoplasty with the Hinderer technique. Subjective (oral respiration,
      epistaxis, rhinorrhea, and nasal obstruction) and objective (anterior
      rhinomanometry) parameters were analyzed and compared between groups. Better
      results in obstructive deflections were achieved with the modified mattress
      suture technique. Unilateral and total nasal resistances improved during the 6
      month follow-up in patients who underwent anterior septoplasty with the modified
      mattress suture technique, and there was a significant difference in the values
      when compared with patients who underwent anterior septoplasty with rhinoplasty
      using the Hinderer technique (p = 0.003). The modified mattress suture technique
      had better subjective and objective results than rhinoplasty with the Hinderer
      technique and therefore could be considered as an alternative technique in
      anterior septal surgery.

PMID- 15509931
TI  - Aesthetic outcomes in patients undergoing breast conservation therapy for the
      treatment of localized breast cancer.
AB  - Localized breast cancer can be treated with lumpectomy and postoperative
      radiation therapy, also called breast conservation therapy, with an efficacy
      equivalent to that of mastectomy. Reports evaluating the effects of radiotherapy
      suggested that breast conservation therapy had "acceptable" cosmetic outcomes;
      thus, posttreatment evaluation for aesthetic impact has not been instituted as a
      standard of care. More recent reports have suggested that the effect of breast
      conservation therapy on aesthetic outcome is not minimal and that patients may
      benefit from reconstructive consultation. The purpose of this study was to
      measure objectively the aesthetic change in women who undergo breast conservation
      therapy and whether the extent of change is significant enough (objectively and
      subjectively) to warrant plastic surgery consultation. The authors evaluated 21
      patients who had undergone breast conservation therapy. Eleven non-breast cancer
      patients seeking plastic surgery consultation were used as controls. Standardized
      five-view photographs (frontal, left and right lateral, and left and right
      lateral oblique views) were obtained. Patient photograph sets were compiled and
      evaluated independently by eight reviewers (four surgeons, two nurses, and two
      medical students). Reviewers evaluated the photographs using the breast asymmetry
      score (score range, 0 to 9) assessing breast size, ptosis, nipple-areola
      position, shape, scar appearance, contour deformity, and skin changes. The
      authors considered 2 SD above the control mean as significant. Breast
      conservation therapy patients also completed a 15-item questionnaire targeting
      objective and subjective data about treatment-related breast change. Breast
      conservation therapy patients had an average treatment-related asymmetry score of
      1.93, with 35 percent demonstrating significant change as compared with controls.
      Although most patients (86 percent) were satisfied with the cancer treatment
      outcome, all patients noted asymmetry. The authors' data indicate that breast
      conservation therapy can cause significant asymmetry; thus, an option for plastic
      surgery consultation as part of the treatment protocol is warranted.

PMID- 15509932
TI  - Extending the reach of the heterodigital arterialized flap by vein division and
      repair.
AB  - The heterodigital arterialized flap is ideal for nonsensory reconstruction of
      sizable soft-tissue defects in the proximal fingers, web spaces, and the hand.
      The inclusion of a dorsal vein augments the venous drainage of this digital
      island flap and avoids the problem of postoperative venous congestion, which is a
      common problem in digital island flaps. However, the presence of a dorsal vein
      pedicle inhibits flap mobility somewhat, and the reach of the flap is mainly
      limited to adjacent fingers. In situations that demand a transfer from a
      nonadjacent donor finger or when the reach from the adjacent donor finger is
      inadequate, the dorsal vein pedicle can be temporarily divided and then
      anastomosed microsurgically after flap transfer is performed. This enables the
      reach of the flap to be extended up to two fingers from the donor finger. The
      authors performed this "partially free" heterodigital arterialized flap in 11
      consecutive patients between 1991 and 2001. The average size of the defects was
      4.4 x 2.3 cm. All of the flaps survived completely, without any evidence of
      postoperative flap congestion. Healing of all of the flaps was primary and did
      not result in any scarring. All of the donor fingers had "normal" two-point
      discrimination of 3 to 5 mm. All of the donor fingers retained excellent or good
      total active motion, as graded by the criteria of Strickland and Glogovac.

PMID- 15509933
TI  - One-stage reconstruction of composite bone and soft-tissue defects in traumatic
      lower extremities.
AB  - Management of bone loss that occurs after severe trauma of open lower extremity
      fractures continues to challenge reconstructive surgeons. Sixty-one patients who
      had 62 traumatic open lower extremity fractures and combined bone and composite
      soft-tissue defects were treated with the following protocol: extensive
      debridement of necrotic tissues, eradication of infection, and vascularization of
      osteocutaneous tissue for one-stage bone and soft-tissue coverage reconstruction.
      The mechanism of injury included 49 motorcycle accidents (80.3 percent), five
      falls (8.2 percent), three crush injuries (4.9 percent), two pedestrian
      automobile accidents (3.3 percent), and two motor vehicle accidents (3.3
      percent). The bone defects were located in the tibia in 49 patients (79 percent;
      one patient had bilateral open tibial fractures), in the femur in seven patients
      (11.3 percent), in the calcaneus bone in four patients (6.5 percent), and in the
      metatarsal bones in two patients (3.2 percent). The size of soft-tissue defects
      ranged from 5 x 9 cm to 30 x 17 cm. The average length of the preoperative bony
      defect was 11.7 cm. The average duration from injury to one-stage reconstruction
      was 27.1 days, and the average number of previous extensive debridement
      procedures was 3.4. Fifty patients had vascularized fibula osteoseptocutaneous
      flaps, six had vascularized iliac osteocutaneous flaps, and five patients had
      seven combined vascularized rib transfers with serratus anterior muscle and/or
      latissimus dorsi muscle transfers. One patient received a second combined rib
      flap because the first combined rib flap failed. The rate of complete flap
      survival was 88.9 percent (56 of 63 flaps). Two combined vascularized rib
      transfers with serratus anterior muscle and latissimus dorsi muscle flaps were
      lost totally (3.2 percent) because of arterial thrombosis and deep infection,
      respectively. Partial skin flap losses were encountered in the five fibula
      osteoseptocutaneous flaps (7.9 percent). Postoperative infection for this one
      stage reconstruction was 7.9 percent. Excluding the failed flap and the
      infected/amputated limb, the primary bony union rate after successful free
      vascularized bone grafting was 88.5 percent (54 of 61 transfers). The average
      primary union time was 6.9 months. The overall union rate was 96.7 percent (59 of
      61 transfers). The average time to overall union was 8.5 months after surgery.
      Seven transferred vascularized bones had stress fractures, for a rate of 11.5
      percent. Donor-site problems were noted in six fibular flaps, in two iliac flaps,
      and in one rib flap. The fibular donor-site problems were foot drop in one
      patient, superficial peroneal nerve palsy in one patient, contracture of the
      flexor hallucis longus muscle in two patients, and skin necrosis after split
      thickness skin grafting in two patients. The iliac flap donor-site problems were
      temporary flank pain in one patient and lateral thigh numbness in the other. One
      rib flap transfer patient had pleural fibrosis. Transfer of the appropriate
      combination of vascularized bone and soft-tissue flap with a one-stage procedure
      provides complex lower extremity defects with successful functional results that
      are almost equal to the previously reported microsurgical staged procedures and
      conventional techniques.

PMID- 15509934
TI  - A new flap design: neural-island flap.
AB  - This report introduces the "neural-island flap" concept, which represents a
      consistent and reliable skin flap design supplied only by the intrinsic
      vasculature of a cutaneous nerve. In this study, the lateral femoral cutaneous
      nerve was selected as the pedicle of the neural-island flap, and a standard skin
      flap, which is the territory of the accompanying vessels (i.e., iliac branches of
      the iliolumbar artery and vein), was elevated on the lower dorsal region of the
      rats. In a total of 92 Wistar rats, three experiments were performed. In part I
      (n = 24), the vascular anatomy of the lateral femoral cutaneous nerve was
      established by the methods of dissection, microangiography, nerve mapping,
      perfusion with colored latex and India ink, and histologic analysis. In part II
      (n = 46), the role of the cutaneous nerve in supporting an acutely elevated skin
      flap was explored by creating five flap groups as follows: group 1, conventional
      flap (artery, vein, and nerve intact); group 2, neural island flap (only the
      nerve intact); group 3, neurocutaneous flap (vein and nerve intact); group 4,
      denervated flap (artery and vein intact); and group 5, skin graft. In part III (n
      = 22), the role of a preliminary surgical delay procedure to augment the survival
      of the neural island flap was investigated. Results of the anatomic studies
      indicated a consistent perineural vasculature by the accompanying iliolumbar
      artery. Skin flaps survived totally in groups where the artery and vein were
      intact, whereas mean survival rates for the neural island flap and the
      neurocutaneous flap were 38.2 +/- 3.1 percent and 44.5 +/- 3.8 percent,
      respectively (p > 0.05). Results of part III of the experiment demonstrated a
      significantly higher survival for the delayed neural island flap (94.5 +/- 5.5
      percent) compared with the acutely elevated neural island flap (p < 0.05). The
      perineural and intraneural vessels were found to be greatly dilated after a delay
      procedure, demonstrated by direct observation, microangiography, histologic
      analysis, dye injection study, and scanning electron microscopy. On the basis of
      this promising series of experiments, a clinical technique was developed using
      the sural neural-island flap. The flap was used to reconstruct lower extremity
      defects in four cases. A delay procedure was accomplished in the first stage by
      elevating a fasciocutaneous flap from the midcalf region based on a posterior
      skin bridge and the sural nerve. After a 2-week delay period, a sural neural
      island flap was created based on the nerve and transposed to the defect. Flap
      survival was complete in all cases, with a satisfactory result. The authors
      conclude that this report proves for the first time that a robust and reliable
      skin flap can be created pedicled only by the intrinsic vasculature of a
      cutaneous nerve, after a proper surgical delay. The so-created neural-island flap
      design offers two novel advantages: (1) a very narrow pedicle and (2) a pedicle
      without any restriction to a specific pivot point, in addition to the previously
      described unique advantages of preservation of a major artery and avoidance of
      microvascular anastomoses.

PMID- 15509935
TI  - Distally based lateral supramalleolar adipofascial flap for reconstruction of the
      dorsum of the foot and ankle.
AB  - Soft-tissue reconstruction of the dorsum of the foot and ankle has long been a
      challenge for reconstructive surgeons. Limitations in the available local tissue
      and donor-site morbidity restrict the options. In an effort to solve these
      difficult problems, the authors have begun to use a distally based lateral
      supramalleolar adipofascial flap. This report presents the authors' early
      experience with seven patients treated with this flap. The patients' ages ranged
      from 5 to 26 years; four of the patients were male and three were female. The
      cause of the soft-tissue defects involved acute trauma and chronic scar
      contracture. The flap and the adjoining raw area were covered with a full
      thickness skin graft, and the donor site at the lateral aspect of the leg was
      closed primarily without grafting. A skin graft was taken from the groin area,
      which was closed primarily. Compared with the other flaps, this adipofascial flap
      was thinner and produced less bulkiness to the recipient site and minor aesthetic
      sequelae to the donor site. It is believed that this flap is versatile and
      effective and is a good addition to the available techniques used by
      reconstructive surgeons for coverage of the dorsum of the foot and ankle.

PMID- 15509936
TI  - Digital glomus tumors: a 29-year experience with a lateral subperiosteal
      approach.
AB  - The excision of distal digital glomus tumors has traditionally been performed
      directly over the involved nail bed. This can lead to nail deformities that are
      often unacceptable for the surgeon and the patient. The authors describe their
      experience with successful excision of digital glomus tumors using a lateral
      subperiosteal approach, which creates a dorsal flap. In 29 years, 19 patients
      were diagnosed with digital glomus tumors. All patients underwent excision using
      the lateral subperiosteal approach. The mean tumor size was 0.52 cm. The tumors
      were located on the pulp of the distal phalanx in two patients (10.5 percent) and
      subungually in 17 patients (89.5 percent). In all patients, preoperative clinical
      diagnosis was confirmed postoperatively with the biopsy result. Complications
      occurred in only two patients and included one paronychia and one temporary nail
      loss. The overall recurrence rate was 15.7 percent. All patients remained
      asymptomatic after surgery and regained full active and passive range of motion.
      There were no nail deformities by this approach. This technique represents a safe
      and effective approach to excising digital glomus tumors.

PMID- 15509937
TI  - Comparison of canine mandibular bone regeneration by distraction osteogenesis
      versus acute resection and rigid external fixation.
AB  - The present study was performed (1) to explore the mechanism of skeletal healing
      following distraction osteogenesis of the mandible and to evaluate whether the
      same process is involved following acute mandibular resection and rigid external
      fixation, and (2) to examine the role of the periosteum in skeletal healing in
      both models. The study was performed using 16 mongrel dogs divided into two equal
      groups. In the first group, distraction of 20 mm was performed at a rate of 1
      mm/day. In the second group, bone resection of 20 mm was performed, followed by
      rigid external fixation. The buccal periosteum was stripped in four dogs from
      each group, and the periosteum was left intact in the remaining four dogs. Dogs
      were euthanized after a survival period of either 2 or 3 months, and the new bone
      regenerate was evaluated. Analysis consisted of three-dimensional computed
      tomography scanning, histometric analysis, and immunostaining. Analysis of bone
      mineral content in the residual gap was conducted. Bone mineral content was
      increased in 3- versus 2-month survival for all groups (p < 0.05). The distracted
      groups had greater bone mineral content than their acutely resected counterparts,
      with the difference achieving statistical significance by 3-month survival (p <
      0.05). Although periosteal preservation resulted in increased bone mineral
      content over time for all groups (p = 0.044), periosteal preservation had no
      significant effect on bone mineral content in the distracted groups. After
      periosteal stripping, however, bone mineral content was significantly increased
      in dogs that underwent distraction rather than acute resection and rigid external
      fixation (p = 0.022). Regarding histometric analysis, analysis of fibrous tissue
      content in the bone regenerate demonstrated that by 3 months the distracted
      groups had significantly less fibrous tissue in the new bone regenerate than did
      the acutely resected groups (p < 0.001). Regarding immunostaining, diffuse
      localization of transforming growth factor-beta1 was observed in all groups at 2
      months, returning to nearly baseline levels by 3 months. These data demonstrate
      that significant bone formation in a segmental gap can be achieved after acute
      mandibular resection and rigid external fixation if the periosteum is preserved.
      However, after periosteal injury or stripping, significant bone formation can
      only be achieved by distraction osteogenesis. In both processes, bone formation
      is preceded by up-regulation of transforming growth factor-beta1.

PMID- 15509939
TI  - Platelet quantification and growth factor analysis from platelet-rich plasma:
      implications for wound healing.
AB  - Growth factors released from activated platelets initiate and modulate wound
      healing in both soft and hard tissues. A recent strategy to promote the wound
      healing cascade is to prepare an autologous platelet concentrate suspended in
      plasma, also known as platelet-rich plasma, that contains growth factors and
      administer it to wound sites. The purpose of this study was to quantitate
      platelet number and growth factors released from a prepared platelet concentrate.
      Whole blood was drawn from 10 healthy patients undergoing cosmetic surgery and
      concentrated into platelet-rich plasma. Platelet counts on whole blood and
      platelet-rich plasma were determined using a Cell-Dyn 3200. Platelet-derived
      growth factor-BB, transforming growth factor-beta1, vascular endothelial growth
      factor, endothelial growth factor, and insulin-like growth factor-1 were measured
      in the platelet-rich plasma using the enzyme-linked immunosorbent assay method.
      In addition, platelet activation during the concentration procedure was analyzed
      by measuring P selectin values in blood serum. An 8-fold increase in platelet
      concentration was found in the platelet-rich plasma compared with that of whole
      blood (baseline whole blood, 197 +/- 42 x 10 platelets/microl; platelet
      concentrate, 1600 +/- 330 x 10 platelets/microl). The concentration of growth
      factors also increased with increasing platelet number. However, growth factor
      concentration varied from patient to patient. On average for the whole blood as
      compared with platelet-rich plasma, the platelet-derived growth factor-BB
      concentration increased from 3.3 +/- 0.9 ng/ml to 17 +/- 8 ng/ml, transforming
      growth factor-beta1 concentration increased from 35 +/- 8 ng/ml to 120 +/- 42
      ng/ml, vascular endothelial growth factor concentration increased from 155 +/-
      110 pg/ml to 955 +/- 1030 pg/ml, and endothelial growth factor concentration
      increased from 129 +/- 61 pg/ml to 470 +/- 320 pg/ml. No increase was found for
      insulin-like growth factor-1. In addition, no increase in platelet activation
      occurred during the concentration procedure as determined by the platelet surface
      receptor P selectin (45 +/- 16 pg/ml to 52 +/- 11 pg/ml, p = 0.65). In
      conclusion, a variety of potentially therapeutic growth factors were detected and
      released from the platelets in significant levels in platelet-rich plasma
      preparations. Sufficient concentrates and release of these growth factors through
      autologous platelet gels may be capable of expediting wound healing in a variety
      of as yet undetermined specific wound applications.

PMID- 15509940
TI  - Reconstruction of ablated rat rectus abdominis by muscle regeneration.
AB  - Skeletal muscle regeneration is a powerful, naturally occurring process of tissue
      reconstruction that follows myofiber damage secondary to myotoxic injury that
      does not normally affect the tissue circulation and scaffold. The ablated tissue,
      in traumatology and free muscle grafts, is frequently replaced by scars. The
      final outcome is poor even after in situ myoblast seeding of the harvested
      muscle. The goal of this study was to identify protocols to reconstruct muscle
      tissue, even in such adverse environments. The authors applied a step-by-step
      approach to identify factors favoring the survival of autologous satellite cells
      and, thus, muscle regeneration. In a rat model of full-thickness rectus abdominis
      muscle ablation, autologous myoblasts were isolated from the explanted rectus
      abdominis and seeded in a homologous acellular matrix immediately after wall
      reconstruction (group 1, five animals). In group 2 (five animals), the ablated
      rectus abdominis was autografted in situ. In a third group of five rats, Marcaine
      was injected into both the autograft and the surrounding abdominal wall muscle.
      Three weeks after surgery, serial cross-sections of the reconstructed abdominal
      wall were stained with hematoxylin and eosin or embryonic myosin antibody, a well
      characterized molecular marker of early myogenesis in development and
      regeneration. Percentages of the patch area covered by regenerated myofibers were
      determined by morphometry. When autologous myoblasts were seeded in a homologous
      acellular matrix, the only myofibers observed to regenerate were those along the
      border of the patch. Autografting of the middle third of the rectus abdominis
      muscle similarly resulted in scar formation. The few muscle cells in the graft
      core were scanty myoblasts that could be detected only by monoclonal embryonic
      myosin antibody. Although negative for myofiber regeneration, the results in both
      cases confirmed the mechanical patency of the patches with regard to abdominal
      organ support. Myofibers were successfully regenerated in the graft by injecting
      Marcaine into both the autograft and the surrounding muscles. Three weeks after
      surgery, the patch was paved with young, centrally nucleated myofibers intermixed
      with young myofibers and myotubes expressing embryonic myosin. The difference in
      percentage of patch area covered by regenerated myofibers in group 3 (Marcaine
      injection around the patch, 81.6 +/- 3.0 percent) (mean +/- SD) versus either
      group 1 (Myoblast-seeded acellular patch, 18.0 +/- 3.0 percent) or group 2
      (Autograft, 25.8 +/- 7.0 percent) was statistically significant on independent t
      test analysis (p < 0.0001). Even an acellular matrix showed some myofiber
      regeneration after surrounding muscles had been injected with Marcaine. This is
      the first successful evidence of muscle reconstruction after full-thickness
      ablation of the middle third of the rectus abdominis. Muscle regeneration seems
      to be the result of successive waves of migration of angioblasts and then
      satellite cell-derived myoblasts from the muscles surrounding the patch. The
      results strongly suggest that vascularization of the scaffold and successive
      coordinate proliferation of the seeded cells are required for myoblasts to be
      able to migrate into the patch and differentiate up to myofiber stage.

PMID- 15509942
TI  - Successful repair of ectopia cordis using alloplastic materials: 10-year follow
      up.

PMID- 15509943
TI  - Autologous cultured skin substitutes conserve donor autograft in elective
      treatment of congenital giant melanocytic nevus.

PMID- 15509944
TI  - The buccal fat pad flap for periorbital reconstruction: a cadaver dissection and
      report of two cases.

PMID- 15509945
TI  - Tumor excision and reconstruction of the upper cervical spine: a
      multidisciplinary approach.

PMID- 15509946
TI  - The cone flap: a new and versatile fasciocutaneous flap.

PMID- 15509947
TI  - Corona glans clitoroplasty and urethropreputial vestibuloplasty in male-to-female
      transsexuals: the vulval aesthetic refinement by the Andalusia Gender Team.
AB  - For more than a decade the pedicled island neurovascular flap of the glans penis
      has been the standard procedure for clitoroplasty in intersex anomalies and in
      male-to-female genital sex reassignment surgery. Most authors focusing on
      genitoperineal reconstructions have used the island neurovascular flap of the
      dorsal shaft of the penis, including a variable-sized dorsal chip of the glans
      penis as the distal and functional portion of the flap. Although this dorsal
      glans clitoroplasty technique for neoclitoral reconstruction is well known, it
      nevertheless deserves scientific revision, with a view to improving several
      neglected aesthetic and functional points. The authors describe a new method for
      reconstruction of the neoclitoris in male-to-female transsexuals, the corona
      glans clitoroplasty. It is based on a modification of the original pedicled
      island neurovascular flap of the glans penis. The main difference compared with
      the dorsal glans clitoroplasty is that, distally, this method includes a bifid
      dorsolateral coronal flap designed in the shape of an open lotus flower or a
      bull's horns. Furthermore, a semicircular preputial flap is retained, attached to
      the bifid coronal flap of the glans, to improve the cosmetic appearance of the
      vestibulum and avoid growth of hair around the neoclitoris. Finally, a small
      dorsal flap of the spongiomucosa urethra designed in the shape of a pencil tip is
      added to improve the cosmetic appearance of the vestibulum between the
      neoclitoris and the urethral neomeatus. Since October of 1999, the authors have
      performed more than 30 genital sex reassignment surgeries in male-to-female
      transsexuals, of whom 16 underwent their technique of corona glans clitoroplasty.
      The authors describe and discuss the anatomic basis and clinical implications of
      this technique and its cosmetic and potential functional advantages. They also
      consider the anatomic differences among four distal designs of the pedicled
      island neurovascular flap of the glans penis: dorsal, lateral, ventral, and
      corona glans clitoroplasty in male-to-female transsexuals.

PMID- 15509948
TI  - Nipple-sparing total mastectomy of large breasts: the role of tissue expansion.

PMID- 15509949
TI  - Long-term follow-up of reconstruction of four metatarsal bone and soft-tissue
      defects using a serratus anterior muscle rib osteomyocutaneous free flap.

PMID- 15509950
TI  - Advanced technologies in plastic surgery: how new innovations can improve our
      training and practice.
AB  - Over the last two decades, virtual reality, haptics, simulators, robotics, and
      other "advanced technologies" have emerged as important innovations in medical
      learning and practice. Reports on simulator applications in medicine now appear
      regularly in the medical, computer science, engineering, and popular literature.
      The goal of this article is to review the emerging intersection between advanced
      technologies and surgery and how new technology is being utilized in several
      surgical fields, particularly plastic surgery. The authors also discuss how
      plastic and reconstructive surgeons can benefit by working to further the
      development of multimedia and simulated environment technologies in surgical
      practice and training.

PMID- 15509951
TI  - A moment of silence.

PMID- 15509952
TI  - The two essential elements for planning tip surgery in primary and secondary
      rhinoplasty: observations based on review of 100 consecutive patients.
AB  - Nasal tip surgery has become significantly more complex since the introduction of
      tip grafting and the many suture designs that followed the resurgence of open
      rhinoplasty. Independent of the surgeon's technical approach, however, is the
      need to identify the critical anatomical characteristics that will make nasal tip
      surgery successful. It is the author's contention that only two such features
      require mandatory preoperative identification: (1) whether the tip is adequately
      projecting and (2) whether the alar cartilage lateral crura are orthotopic or
      cephalically rotated ("malpositioned"). Data were generated from a review of 100
      consecutive primary rhinoplasty patients on whom the author had operated. The
      results indicate that only 33 percent of the entire group had adequate
      preoperative tip projection and only 54 percent had orthotopic lateral crura
      (axes toward the lateral canthi). Forty-six percent of the patients had lateral
      crura that were cephalically rotated (axes toward the medial canthi). Both
      inadequate tip projection and convex lateral crura were more common among
      patients with malpositioned lateral crura (78 percent and 61 percent) than in
      patients with orthotopic lateral crura (57 percent and 20 percent, respectively).
      Tip projection can be reliably assessed by the relationship of the tip lobule to
      the septal angle. Malposition is characterized by abnormal lateral crural axes,
      long alar creases that extend to the nostril rims, alar wall hollows, frequent
      nostril deformities, and associated external valvular incompetence. The data
      suggest that the surgeon treating the average spectrum of primary rhinoplasty
      patients will see a majority (61 percent) who need increased tip support and a
      significant number (46 percent) with an anatomical variant (alar cartilage
      malposition) that places these patients at special risk for postoperative
      functional impairment. Correction of external valvular incompetence doubles nasal
      airflow in most patients. As few as 23 percent of primary rhinoplasty patients
      (the number with orthotopic, projecting alar cartilages in this series) may be
      proper candidates for reduction-only tip procedures. When tip projection and
      lateral crural orientation are accurately determined before surgery, nasal tip
      surgery can proceed successfully and secondary deformities can be avoided.

PMID- 15509954
TI  - Effects of aesthetic abdominoplasty on abdominal wall perfusion: a quantitative
      evaluation.
AB  - Abdominoplasty procedures involve a high risk of early complications, including
      hematomas, seromas, necrosis, and wound-healing problems. Their rationale is
      evident from the vascular anatomy of the abdominal wall, as traditional
      abdominoplasty includes a division of the main perforating vessels. No studies
      exist to quantitatively assess the consequences of abdominoplasty on the
      perfusion of the random pattern abdominal flap. To address this issue and
      quantify the influence of classic abdominoplasty on the perfusion of the
      abdominal skin, the authors performed a prospective clinical trial including 15
      low-risk patients undergoing abdominoplasty for aesthetic purposes. Perfusion of
      the abdominal flap was measured intraoperatively using the technique of dynamic
      laser-fluorescence-videoangiography. In the region between the umbilicus and the
      transverse scar (zone 1), the increment of fluorescence (the slope of the
      intensity curve during inflow of the indocyanine green) was recorded and compared
      with the intensity curve of normal tissue that was not involved in surgery
      (thoracic wall). The results of the intraoperative indocyanine green
      perfusography showed a significant impairment of the vascular supply of zone 1 in
      all patients. The mean perfusion index in this region was 17.2 percent (range, 5
      to 32 percent) of the perfusion of the surrounding skin that was not involved in
      surgery. The complication rate was 33 percent (five patients) and included two
      cases of hematoma and three cases of scar dehiscence with skin and/or fat
      necrosis. These data indicate that conventional abdominoplasty including extended
      undermining and division of the superficial and the deep arterial systems causes
      profound devascularization of the abdominal flap. This might explain the high
      incidence of complications following this procedure.

PMID- 15509955
TI  - Subperiosteal brow lifts without fixation.
AB  - Most surgeons today advocate an endoscopic subperiosteal brow lift for surgical
      correction of the upper third of the face. At the author's clinic, this operation
      has been performed since 1994 and the subgaleal bicoronal brow lift is no longer
      used. In earlier investigations, the author showed that the subperiosteal
      approach (n = 60) gives a better result than the subgaleal method (n = 60) when
      compared 1 year after surgery. In the literature, however, there are no published
      data regarding the long-term results of subperiosteal brow lifts. The author took
      material from his earlier investigations and looked at the same patients 5 years
      postoperatively. He compared the subperiosteal approach (n = 30) with the
      subgaleal brow lift (n = 15) and found that after 5 years the brows of the
      subgaleal patients were on the same level as they were before surgery, but in the
      group of subperiosteal brow lifts, almost all of the brows were higher 5 years
      after surgery than they were 1 year after surgery, with a mean increase in height
      of 2.5 mm. These findings led the author to the question whether scalp fixation
      was necessary at all when performing a subperiosteal brow lift. He performed 20
      subperiosteal endoscopic brow lifts where scalp fixation was not used at all,
      relying only on changing the balance of muscle vectors around the eyebrows. Using
      a computerized instrument, measurements were made of the distance between the
      medial canthus and the top of the eyebrow, the midpupil and the top of the
      eyebrow, and the lateral canthus and the top of the eyebrow. All patients were
      measured before and 1 year after surgery. The author found an increase of the
      vertical height from the midpupil to the top of the brow, with an average
      increase of 3.9 mm. There were no differences between patients who had only a
      brow lift and those who had a brow lift and an upper blepharoplasty at the same
      time. The author concludes that for most cases where an increased vertical height
      of the brows of more than 4 mm is not needed, it is not necessary to use scalp
      fixation to achieve a natural result.

PMID- 15509957
TI  - Buttock augmentation: case studies of fat injection monitored by magnetic
      resonance imaging.
AB  - This article examines the injection of megavolumes of autologous fat cells as a
      means of buttock augmentation in 162 patients over a 7-year period. The author
      documents the use of magnetic resonance imaging in six patients to visualize the
      intramuscular location, integration, and duration of the injected fat. With the
      patient under epidural or general anesthesia, fat cells were harvested with a 5
      mm blunt cannula and then stored in an empty sterile intravenous bag or bottle
      trap. Decantation was the only process used to separate the fat cells from the
      saline and serosanguineous components. Up to 1260 cc of fat cells were been
      injected into each buttock, the largest amount of fat grafting ever reported.
      Clinical assessment estimated a 20 percent loss of augmentation effect during the
      first 4 months. Patients were generally pleased with the final shape and volume
      of the buttock contour. In follow-up evaluation, magnetic resonance imaging
      supported the clinical indicators that the injection of large quantities of fat
      cells appears to be a safe and effective method for buttock enhancement. This
      process has inherent advantages; nevertheless, further research is required to
      clarify our understanding of the predictability and longevity of this technique.

PMID- 15509959
TI  - Breast augmentation using the spectrum implant with exteriorized injection domes.
AB  - The author describes the use of implants with exteriorized injection domes for
      patients undergoing breast augmentation. Domes were exteriorized for 1 to 5 days
      to allow the implant volume to be altered in the early postoperative period.
      Thirty-three patients were treated without any infections.

PMID- 15509961
TI  - The limited scar mastopexy: current concepts and approaches to correct breast
      ptosis.
AB  - The literature on short scar mastopexy was reviewed, with a focus on the
      different techniques. Currently four techniques have been described: the
      periareolar, the vertical, the inverted-T, and the L-shaped scar. The different
      techniques were evaluated with regard to patient selection, operative techniques,
      scar length, and complications. A large number of techniques have been published
      for minimal ptosis, whereas for significant ptosis, the number of surgical
      options is limited. It is evident that limited scar techniques can be applied to
      all grades of ptosis, but there is no one technique that can satisfactorily
      correct all degrees of ptosis. Plastic surgeons should weigh the advantages and
      limitations of each technique to correctly address breast ptosis. This article
      reviews an algorithmic approach to correct all degrees of ptosis with mastopexy.

PMID- 15509962
TI  - Minibrachioplasty: minimizing scars while maximizing results.
AB  - The growing popularity of bariatric surgery has increased the number of
      brachioplasties performed. One of the major drawbacks of brachioplasty is the
      unsatisfactory appearance of the surgical scar. The author describes a short-scar
      brachioplasty, or minibrachioplasty, that can achieve much of the improvement of
      a traditional brachioplasty while concealing the scars within the confines of a
      short-sleeve shirt or blouse. Eight patients treated with this technique saw a
      significant improvement in the appearance of their upper arms.

PMID- 15509964
TI  - A ten-year evaluation following corrections of implant ptosis subsequent to
      transaxillary subpectoral breast augmentation.

PMID- 15509966
TI  - Lessons in morality and mortality.

PMID- 15509967
TI  - How much do you need to know?

PMID- 15509970
TI  - Adipose compartments of the upper eyelid: anatomy applied to blepharoplasty.

PMID- 15509971
TI  - Gold implants for lagophthalmos.

PMID- 15509974
TI  - Schwannoma of the tip of the tongue in a child.

PMID- 15509972
TI  - Pressure sore of the helical rim: a new problem, a novel treatment.

PMID- 15509975
TI  - Surgical smoke without fire: the risks to the plastic surgeon.

PMID- 15509976
TI  - A novel model for skin graft harvesting.

PMID- 15509978
TI  - Massive weight loss after bariatric surgery: friend or foe?

PMID- 15509977
TI  - Salvage of baclofen pump pocket infection with muscle flap.

PMID- 15509979
TI  - The treatment of burn disease in the Hippocratic era.

PMID- 15509980
TI  - Nylon tape as a ganglion lasso.

PMID- 15509981
TI  - Handmade suction device with small pieces of microsponge to keep the difficult
      anastomotic site clear in microvascular surgery.

PMID- 15509982
TI  - Reducing surgical hazard associated with the Kleinert's "cat's paw" retractor.

PMID- 15509983
TI  - A sponge model for flap surgery.

PMID- 15509984
TI  - Stress-related gastric bleeding after rhinoplasty.

PMID- 15509985
TI  - Dog bites in Oakland, California.

PMID- 15509987
TI  - Pharyngeal flap surgery: long-term outcomes at the University of Iowa.

PMID- 15509988
TI  - Avoiding areolar distortion in drape pattern reduction mammaplasty.

PMID- 15509989
TI  - Digital anesthesia via a single subcutaneous injection.

PMID- 15509990
TI  - Simplifying the vertical reduction mammaplasty.

PMID- 15509992
TI  - Chronic finger constriction by completely embedded rings: one ring may hide
      another.

PMID- 15509993
TI  - Countering the "accordion effect" in flexor tendon repair.

PMID- 15509995
TI  - Is nail germinal matrix ablation always necessary in a dorsal reverse
      adipofascial flap procedure for fingertip reconstruction?

PMID- 15509996
TI  - Metastatic bronchogenic carcinoma of the hand.

PMID- 15509998
TI  - Management of adduction contracture of the thumb with a prefabricated radial
      fascial flap.

PMID- 15509999
TI  - Nail bed secured with a syringe splint.

PMID- 15510000
TI  - Functional reconstruction of the thumb after resection of a slowly growing
      chondrosarcoma.

PMID- 15510001
TI  - Electrothermal ring burn.

PMID- 15510002
TI  - Third-degree burn after plaster of Paris brace.

PMID- 15510003
TI  - Humanitarian missions in the third world.

PMID- 15510004
TI  - Breast reduction insurance denials.

PMID- 15510005
TI  - Local anesthesia saves lives of experimental rats and time and money of
      researchers in composite tissue allotransplantation.

PMID- 15510007
TI  - A method that deals with the presence of hair in animals used for research.

PMID- 15510008
TI  - Enhancement of Ad-p53 therapy with docetaxel in head and neck cancer.
AB  - OBJECTIVE: The objective of this project was to determine the mechanisms in which
      docetaxel enhances Ad-p53 tumor suppressive effects in head and neck cancer.
      BACKGROUND: In advanced head and neck squamous cell carcinoma (HNSCC), the 5-year
      survival rate is less than 40%. Because patients with advanced HNSCC have a high
      rate of local-regional failure (40-60%) with existing treatment modalities,
      aggressive local therapy approaches need to be developed. Previous data show that
      docetaxel or Ad-p53 alone have significant anti-tumor activity in HNSCC. Before
      testing whether a combination approach (Ad-p53 and docetaxel) could be developed
      in clinical trials, preclinical experiments were performed. METHODS: The p53 gene
      was overexpressed in 2 head and neck squamous carcinoma (HNSCC) cell lines, HN30
      and HN12, and a murine Balb/c mucoepidermoid carcinoma (BMEC) cell line.
      Docetaxel's enhancement of adenoviral transduction (bGAL expression), coxsakie
      adenovirus receptor (CAR) expression, and Ad-p53 induction of apoptosis (Annexin
      V expression) were measured. The modulation of regulators in the cell cycle,
      apoptosis and signal transduction pathways were measured using Western blot.
      RESULTS: Docetaxel increased adenoviral transduction, which was dependent on the
      dose of docetaxel and levels of Ad-bGAL. The enhanced viral transduction was due
      in part to the upregulation of the CAR protein. Pretreatment with docetaxel
      enhanced Ad-p53-induced apoptosis through increased expression of exogenous p53.
      Together, the combination of docetaxel and Ad-p53 altered expression of key
      regulators in the cell cycle, apoptosis and signal transduction pathways with an
      increase in the expression of p53, bax, cleaved PARP, cleaved caspase-3 and
      phosphorylation of c-Jun at position at Ser. Cyclin A and B1 expression were down
      regulated by docetaxel and Ad-p53. When comparing the docetaxel-resistant to
      sensitive cell lines, the altered expression of p27 and skp1 by docetaxel and Ad
      p53 were dissimilar between these cell lines. CONCLUSIONS: Docetaxel enhanced Ad
      p53 transduction and increased expression of exogenous p53 gene transfer,
      apoptosis, and antitumor mechanisms. These results support a clinical combination
      of docetaxel with p53 gene therapy in patients with head and neck cancer.

PMID- 15510009
TI  - The biology and management of subglottic hemangioma: past, present, future.
AB  - OBJECTIVES/HYPOTHESIS: Objectives were 1) to review the presentation, natural
      history, and management of subglottic hemangioma; 2) to assess the affect of five
      variables (age, gender, degree of subglottic narrowing, location and extent of
      subglottic hemangioma, and lack or presence of other hemangioma) and the outcome
      of six different treatment modalities (conservative monitoring, corticosteroid,
      laser surgery, tracheotomy, laryngotracheoplasty, and interferon) in the
      management of subglottic hemangioma; and 3) to present specific guidelines to
      help determine the best possible treatment modality at the time of initial
      presentation. STUDY DESIGN: Retrospective review in the setting of three tertiary
      care pediatric medical centers. METHODS: Methods included 1) extensive review of
      the literature; 2) a systematic review with respect to age, gender, presentation,
      associated medical problems, location and degree of subglottic narrowing, initial
      treatment, need for subsequent treatments, outcome, complications, and prognosis;
      and 3) statistical analysis to determine the effect of five variables (age,
      gender, degree of subglottic narrowing, location and extent of subglottic
      hemangioma, and lack or presence of other hemangioma) and the outcome of six
      different treatment modalities (conservative monitoring, corticosteroid, laser
      surgery, tracheotomy, laryngotracheoplasty, and interferon). RESULTS: In all, 116
      patients with a mean age of 4.7 months were treated. The most common location of
      subglottic hemangioma was the left side. The range of subglottic narrowing was
      10% to 99% (mean percentage, 65%). Twenty-six patients (22%) were managed with a
      single treatment modality, which included conservative monitoring (n = 13),
      corticosteroid (n = 11), and tracheotomy (n = 2). Ninety patients (78%) required
      multimodality treatments. Overall, the treatments included conservative
      monitoring (n = 13), corticosteroid (n = 100), tracheotomy (n = 32), CO2 laser (n
      = 66), interferon (n = 5), and laryngotracheoplasty (n = 25). Complication rates
      included the following: conservative monitoring (none), corticosteroid (18%),
      tracheotomy (none), CO2 laser (12%), interferon (20%), and laryngotracheoplasty
      (20%). The following variables showed statistical significance in the outcome of
      different treatment modality: 1) degree of subglottic narrowing (P < .001), 2)
      location of subglottic hemangioma (P < .01), and 3) presence of hemangioma in
      other areas (P < .005). Gender (P > .05) and age at the time of presentation (P >
      .06) did not show any statistical significance on the outcome of the treatments.
      CONCLUSION: Each patient should be assessed comprehensively, and treatment should
      be individualized based on symptoms, clinical findings, and experience of the
      surgeon. The authors presented treatment guidelines in an attempt to rationalize
      the management of subglottic hemangioma and to help determine the best possible
      treatment modality at the time of initial presentation.

PMID- 15510010
TI  - Coccidioidomycosis causing massive cervical lymphadenopathy.
AB  - Coccidioidomycosis involving the head and neck is uncommon. We present a case of
      a patient with disseminated coccidioidomycosis and massive submandibular cystic
      lymphadenopathy unresponsive to systemic antifungal treatment. It is our
      impression that significant clinical improvement resulted from concomitant needle
      aspiration of the cystic nodes to decrease fungal load and modification of
      systemic medication. Although reduction of fungal burden may provide an improved
      response to antifungal therapy, disseminated coccidioidomycosis is a systemic
      disease that requires appropriate systemic therapy.

PMID- 15510011
TI  - Molecular and cellular staging for the severity of chronic rhinosinusitis.
AB  - OBJECTIVES: To correlate objective and subjective clinical parameters with
      molecular, cellular, and histologic markers and to acknowledge the importance of
      these basic science parameters in a severity classification system for chronic
      rhinosinusitis (CRS). STUDY DESIGN: Retrospective analysis of prospectively
      collected data of consecutive patients undergoing endoscopic sinus surgery for
      CRS in an academic institution. METHODS: The preoperative computed tomography
      (CT) scans of all patients with CRS scheduled for surgery were graded according
      to Lund and Mackay. The patients completed a Sino-Nasal Outcome Test (SNOT)-20
      questionnaire and had a preoperative nasal endoscopy performed, which was graded
      by assigning an endoscopy score according to Lanza and Kennedy. Subjects had a
      medical questionnaire regarding presence of aspirin sensitivity, allergic
      rhinitis, asthma, and medication usage. Subjects also underwent pulmonary
      function testing and had skin tests for allergies. At the time of surgery, blood
      was drawn to determine the level of peripheral eosinophilia and the degree of
      polymorphisms of the leukotriene C4 synthase gene. Sinus mucosal and polyp tissue
      was examined pathologically for the number of eosinophils per high-powered filed
      (HPF) and was stained for EG2 to determine the portion of activated eosinophils.
      Leukotriene C4 levels (pg/g of tissue) were determined using a sensitive
      competitive enzyme immunoassay. Endoscopy and SNOT-20 scores were reevaluated 1
      year after surgery. Data were analyzed for disease-severity correlation to
      recommend a severity classification system for CRS that incorporates the
      contribution of clinical, molecular, cellular, and histologic parameters.
      RESULTS: The presence of polyps resulted in higher preoperative CT scores and
      higher preoperative and postoperative symptom scores. Average preoperative CT
      scores were significantly higher in asthmatics and allergy patients and
      correlated with endoscopy scores. Patients with more than five eosinophils/HPF of
      sinus tissue had higher frequency of polyps and asthma and higher CT and
      endoscopy scores than patients without sinus tissue eosinophilia (less than or
      equal to 5 cells/HPF sinus tissue). The subgroup of patients with eosinophilic
      nasal polyps (eosinophilic hyperplastic rhinosinusitis) had more severe disease
      by CT and endoscopy than the subgroup of patients with nasal polyps (hyperplastic
      rhinosinusitis) but without eosinophilia. Similarly, patients without polyps but
      with tissue eosinophilia had more severe disease than patients without polyps and
      without eosinophilia. Leukotriene C4 levels were elevated in all patient groups.
      Symptom scores did not correlate with any of the parameters. CONCLUSION: We
      suggest the following severity classification system for CRS: 1) eosinophilic
      chronic hyperplastic rhinosinusitis (ECHRS): patients with polyps and sinus
      tissue eosinophilia; 2) noneosinophilic chronic hyperplastic rhinosinusitis
      (NECHRS): patients with polyps but without sinus tissue eosinophilia; 3)
      eosinophilic chronic rhinosinusitis (ECRS): patients without polyps but with
      sinus tissue eosinophilia; 4) noneosinophilic chronic rhinosinusitis (NECRS):
      patients without polyps and without sinus tissue eosinophilia.

PMID- 15510012
TI  - Integration of human papillomavirus type 11 in recurrent respiratory papilloma
      associated cancer.
AB  - OBJECTIVES/HYPOTHESIS: The main objective was to demonstrate that human
      papillomavirus (HPV) type 11 is an aggressive virus that plays a significant role
      in the development of laryngeal cancer in patients with a history of recurrent
      respiratory papillomatosis (RRP). We have done so by preliminary investigation
      into the molecular mechanism underlying the malignant transformation of RRP to
      invasive squamous cell carcinoma. STUDY DESIGN: An experimental, nonrandomized,
      retrospective study using tissue specimens from nine patients with a history of
      RRP that progressed to laryngeal or bronchogenic cancer was performed. METHODS:
      DNA and RNA were extracted from 20 formalin-fixed, paraffin-embedded specimens
      from six patients with a history of early onset RRP and laryngeal cancer and from
      three patients with early onset RRP and bronchogenic cancer. Polymerase chain
      reaction (PCR) was performed on DNA to determine the HPV type in each specimen.
      Reverse-transcriptase PCR specific for virus transcripts was performed on RNA to
      determine whether the viral genome was integrated into the host genome. RESULTS:
      HPV-11 but not HPV-6, 16, or 18 was found in all of the laryngeal and
      bronchogenic cancers in patients with a history of early onset RRP in this study.
      RNA, sufficiently intact for examination, was obtained from seven patients.
      Analysis of HPV 11 transcripts revealed integration of the viral genome in three
      of seven patients. CONCLUSIONS: HPV type 6 and 11 are considered "low-risk"
      viruses and are not associated with genital cancers, as are HPV types 16 and 18.
      However, our data suggests that HPV type 11 is an aggressive virus in laryngeal
      papilloma that should be monitored in patients with RRP.

PMID- 15510013
TI  - Intratympanic injections of dexamethasone for long-term control of vertigo.
AB  - OBJECTIVE: To examine whether intratympanic injection of dexamethasone is
      effective in long-term control of vertigo for patients with Meniere disease whose
      dietary and diuretic therapy has proved unsuccessful. STUDY DESIGN: Retrospective
      chart review performed at Carolina Ear and Hearing Clinic, Raleigh, North
      Carolina. METHODS: Thirty-four patients with intractable Meniere disease were
      given intratympanic injections of corticosteroids using dexamethasone 10 mg/mL
      for 4 weeks. The control of vertigo was documented in the 2-year period after
      completion of the course of injections. All patients were continued on a diet and
      a diuretic during the study period. RESULTS: Only 24% (8 of 34) of patients had
      control of vertigo with a single course of injections. Three patients had control
      of vertigo for 12 months and responded to a repeat series of injections with good
      control. Five patients who had recurrent vertigo at 6 months or earlier responded
      to repeat injections, for a total of 16 patients (47%) whose vertigo was
      controlled with a single course or multiple courses of intratympanic injections
      of corticosteroids. CONCLUSIONS: Approximately one-half of patients (47%) with
      intractable Meniere disease achieved control of vertigo with one or more courses
      of intratympanic injections of corticosteroids. A single course of treatment
      alone can be expected to produce long-term control of vertigo in only one-fourth
      (24%) of patients. This study indicates that intratympanic injections of
      corticosteroids should not be expected to give long-term control of vertigo in
      patients with Meniere disease. Multiple courses of intratympanic injections of
      corticosteroids, in conjunction with other treatments, are necessary in most
      patients with Meniere disease who have intractable vertigo.

PMID- 15510014
TI  - The changing demographics of head and neck squamous cell carcinoma in the United
      States.
AB  - OBJECTIVES/HYPOTHESIS: Head and neck squamous cell carcinoma (HNSCCA) has
      declined in the United States since the late 1970s. During this time, substantial
      immigration from other countries has occurred, and the average lifespan has
      increased. We tested the hypothesis that these trends have altered the HNSCCA
      patient population. STUDY DESIGN: Retrospective analysis was made of population
      based data from the SEER database, a national registry capturing roughly 10% of
      all U.S. cancer diagnoses. METHODS: We examined all unique diagnoses of HNSCCA in
      the database from 1976 to 1999 and determined the breakdown of cases by age, sex,
      and race. RESULTS: The absolute number of new HNSCCA diagnoses per year declined
      overall by 5% during the time period of the study, whereas new diagnoses in
      patients older than 74 years of age increased by more than 20%. The rate of
      HNSCCA per 100,000 person-years in elderly women did not change, and the rate in
      elderly men decreased, indicating that the observed increase in cases is
      explained by a growing population of elderly persons at risk. An increase in the
      absolute number of cases, but not the incidence rate, was also seen among persons
      younger than 50 years of age. Although both the absolute number of new cases and
      the incidence rates of HNSCCA in white male patients declined substantially, the
      percentage of HNSCCA patients classified as minorities increased from 14.5% to
      more than 20% of all cases. During the time period of the study, the overall
      number of HNSCCA cases in nonwhite and Hispanic patients increased by 36%.
      CONCLUSION: Increasing numbers of elderly and minority patients with HNSCCA are
      likely to alter patterns of disease and utilization of health care resources.

PMID- 15510015
TI  - Endoscopic management of hypopharyngeal stenosis after organ sparing therapy for
      head and neck cancer.
AB  - OBJECTIVES: The objective of this study was to describe and evaluate the efficacy
      of an endoscopic technique for the management of postchemoradiation
      hypopharyngeal stenosis in head and neck cancer patients. STUDY DESIGN:
      Retrospective review. METHODS: Patients with postchemoradiation hypopharyngeal
      stenoses were identified from the Dana Farber Cancer Institute head and neck
      database. Patients who had undergone extirpative surgery and reconstruction were
      excluded. All patients underwent either anterograde dilatation (AD) by the lead
      author (C.A.S.) or transgastric retrograde esophagoscopy with anterograde
      dilatation (TREAD) (C.A.S., M.T.J.). Chemoradiation records, clinic notes,
      operative reports, and swallowing test data were reviewed. Removal of the gastric
      feeding tube was considered the endpoint of rehabilitation. RESULTS: Seventeen
      patients had postcricoid stenoses identified by modified barium swallow.
      Endoscopy confirmed 15 postcricoid stenoses and 2 proximal esophageal stenoses.
      Nine (53%) patients had partial stenoses, and eight (47%) had complete stenoses.
      Eight partial stenosis patients underwent 10 AD procedures and 3 TREAD
      procedures. Eight complete stenosis patients underwent 9 TREAD procedures and 26
      subsequent AD procedures. Fifteen of 16 (93%) patients resumed swallowing after
      dilatation. Thirteen (81%) patients maintained their weight on an oral diet and
      had their gastric feeding tubes removed. Complications included hypopharyngeal
      perforation (13%), abdominal wall infection (6%), stomach wall dehiscence (6%),
      and chondroradionecrosis of the cricoid cartilage (6%). CONCLUSIONS: Postcricoid
      hypopharyngeal stenosis may be partial or complete after organ sparing
      chemoradiation for head and neck cancer. Using the TREAD technique, successful
      rehabilitation of swallowing can be achieved with a low incidence of
      complications.

PMID- 15510016
TI  - Significance of nasal polyps in chronic rhinosinusitis: symptoms and surgical
      outcomes.
AB  - PURPOSE: To demonstrate the significance of nasal polyps on the symptoms of
      chronic rhinosinusitis (CRS) and their influence on surgical outcomes. METHODS:
      Retrospective analysis of prospectively collected data comparing two groups of
      patients diagnosed with CRS with and without nasal polyps that underwent surgical
      management with a minimum 1-year follow-up period. Subjective scoring was
      performed using the Sino-Nasal Outcome Test (SNOT-20) questionnaire. Computed
      tomography (CT) scans were compared using the Lund-Mackay scoring system. The two
      groups were analyzed for the need of revision surgery. RESULTS: Two hundred one
      patients underwent surgical management of CRS over a 3-year period. One hundred
      four were male, 97 were female, and the average age was 49 (range 18-80) years.
      Polyps were present in 78 patients with CRS, whereas 123 patients did not have
      polyps. The average CT score was 18 for the polyp group and 9.5 for the patients
      without polyps (P = .0000). Nonpolyp group SNOT-20 scores were 26.5
      preoperatively with improvement to 5.1 at 6 months and 5.0 at 12 months
      postoperatively (85% improvement). Polyp group SNOT-20 preoperative scores
      averaged 32.2 with improvement to 9.2 at 6 months and 9.1 at 12 months
      postoperatively (81% improvement, P = .003). Nine patients required revision
      surgery (4.5%), eight (10%) who had polyps and one (0.8%) who did not (P = .002).
      CONCLUSION: The presence of nasal polyps has a significant negative impact on
      patients with CRS. Patients with nasal polyps have more severe symptoms with less
      improvement after operative intervention, higher CT scores at presentation, and a
      significantly higher need for revision surgery.

PMID- 15510017
TI  - Endolymphatic duct violation during retrosigmoid dissection of the internal
      auditory canal: a human temporal bone radiographic study.
AB  - OBJECTIVE/HYPOTHESIS: Successful hearing preservation after acoustic neuroma
      resection is sometimes complicated by delayed hearing deterioration. The goal of
      this study was to investigate the hypothesis that internal auditory canal (IAC)
      drilling during retrosigmoid acoustic neuroma removal may result in endolymphatic
      duct (ELD) injury, a potential cause of delayed hearing loss (HL) after hearing
      preservation surgery. STUDY DESIGN: Temporal bone anatomic and radiographic study
      and literature review. METHODS: Twenty-one human temporal bones were analyzed
      with high-resolution multislice computed tomography (HRMCT) and subjected to
      standard retrosigmoid IAC dissection with labyrinthine preservation and follow-up
      HRMCT for analyses of the ELD. A MEDLINE search was performed of studies
      documenting long-term hearing preservation outcomes after retrosigmoid
      dissection. RESULTS: Five of 21 (24%) bones were found to have violation of the
      ELD despite preservation of labyrinthine structures and the endolymphatic sac.
      These results correlate with the mean incidence of long-term hearing decline
      (26.6%). Reviews of human and animal studies indicate that injury to the ELD may
      create endolymphatic hydrops. CONCLUSIONS: The ELD is vulnerable to injury during
      IAC dissection even if labyrinthine structures at the lateral aspect of the IAC
      are preserved. These findings may be helpful in explaining and potentially
      preventing some cases of long-term hearing deterioration that may be a result of
      endolymphatic hydrops after ELD injury during acoustic tumor removal. Careful
      preoperative review of imaging studies using HRMCT may prove useful before
      retrosigmoid dissection.

PMID- 15510018
TI  - Prevalence of Helicobacter pylori in patients with nasal polyps: a preliminary
      report.
AB  - OBJECTIVES: The aim of the study is to determine the presence of H. pylori in
      nasal polyps by both immunohistochemical staining with H. pylori antibody of
      biopsy specimens and enzyme-linked immunoadsorbent assay (ELISA) of sera. STUDY
      DESIGN: A prospective, controlled, clinical trial. METHODS: We enrolled 30
      patients with nasal polyps and 20 controls with middle concha bullosa undergoing
      endoscopic sinus surgery (ESS). Blood samples of both the study and control
      groups were evaluated for anti-H. pylori specific immunoglobulin (Ig)G antibodies
      by ELISA. In addition, biopsy specimens of the removed polyps and the mucosal
      part of middle conchas were examined by the immunohistochemical analysis with H.
      pylori antibody. RESULTS: In the blood samples, specific IgG antibodies to H.
      pylori were found in 26 (86.7%) of 30 polyp patients and 17 (85%) of 20 controls.
      In 6 (20%) of the 30 patients, H. pylori was identified in the nasal polyp
      tissue, but it was not detected in the mucosal part of the middle concha
      specimens. No significant statistical difference was observed for H. pylori
      antibodies by ELISA among the patients with nasal polyps and the control group
      (Fisher's exact test, P = .59). However, there was a statistical difference
      between the polyp biopsy specimens and the control biopsy specimens by
      immunohistochemical staining (Fisher's exact test, P = .037). CONCLUSIONS: This
      study indicates that H. pylori was found in increased prevalence in the nasal
      polyps. However, further controlled epidemiologic studies would be necessary to
      confirm our results and clarify the potential underlying pathogenetic mechanisms.

PMID- 15510019
TI  - Safety of minimally invasive pituitary surgery (MIPS) compared with a traditional
      approach.
AB  - INTRODUCTION: Transsphenoidal hypophysectomy is becoming progressively less
      invasive. Recent endoscopic techniques avoid nasal or intraoral incisions, use of
      nasal speculums, and nasal packing. Several case series of endoscopic endonasal
      pituitary surgery have been reported, but relatively little data exists comparing
      complication rates to more traditional approaches. We compare the complications
      of our first 50 cases of endoscopic, minimally invasive pituitary surgery (MIPS)
      to our last 50 sublabial transseptal (SLTS) procedures. STUDY DESIGN:
      Retrospective case control study. METHODS: Fifty consecutive MIPS procedures and
      50 consecutive SLTS procedures were reviewed retrospectively. Complication rates
      were analyzed and compared. RESULTS: Total complications per patient (P = .005),
      postoperative epistaxis (P = .031), lip anesthesia (P = .013), and deviated
      septum (P = .028) occurred more often in the SLTS group. No significant
      difference was seen in cerebrospinal fluid leak, meningitis, ophthalmoplegia,
      visual acuity loss, diabetes insipidus, intracranial hemorrhage, or death. In the
      MIPS group, length of stay (P < .001), use of lumbar drainage (P = .007), and
      nasal packing (P < .001) were also significantly reduced. CONCLUSIONS: Endoscopic
      endonasal pituitary surgery provides improved complication rates when compared
      with SLTS approaches. In addition, we note advantages of the MIPS approach,
      including reduced length of hospital stay and decreased use of lumbar drainage
      and nasal packing.

PMID- 15510020
TI  - Viability of a 12-ring complete tracheal segment transferred in the form of a
      compound flap: an experimental study in dogs.
AB  - INTRODUCTION: There is a lack of an ideal substitute for the injured tracheal
      tissues. Autologous or homologous grafts and prostheses are inadequate because of
      their unreliable and nonviable nature for the reconstruction of a complete
      tracheal segment (CTS). OBJECTIVE: We studied the viability of a 12-ring CTS
      transferred in the form of a compound flap from the sternohyoid muscle (SM) for
      tracheal reconstruction. METHODS: Sixteen mongrel dogs of both sexes were divided
      into two groups of eight dogs each. In group I (control), a 12-ring CTS was
      removed and then reimplanted as an autograft. In group II, an SM flap was used to
      envelop four rings of the CTS to produce a compound CTS flap neovascularized by
      the SM (CTSNV). After 21 days, a 12-ring CTSNV, consisting of the four rings
      previously covered with SM, four rings above, and four rings below (without
      muscle covering), was sectioned and completely separated from the trachea. The
      CTS was then reimplanted at its original site, with the SM being the only
      vascular supply pedicle for the flap. RESULTS: The results were evaluated
      clinically and by macroscopic and microscopic examination of the surgical
      specimens. All the animals in group I (control) died or were killed by the first
      or second week because of necrosis and stenosis of the CTS graft. In group II,
      all animals were killed after 77 days of follow-up without showing any alteration
      in the CTSNV. CONCLUSIONS: We conclude that a compound 12-ring CTSNV flap remains
      viable and can be mobilized from the trachea without the risk of necrosis or
      stenosis.

PMID- 15510021
TI  - Basilar membrane displacement related to endolymphatic sac volume.
AB  - OBJECTIVE: To demonstrate that the amount of basilar membrane displacement toward
      the scala tympani and its attachment to the bony wall of the scala tympani (i.e.,
      interscalar septum) in hydropic temporal bones is related to the intraosseous
      endolymphatic sac volume. STUDY DESIGN: A retrospective analysis of temporal
      bones from individuals with the histopathologic diagnosis of "endolymphatic
      hydrops." METHODS: Fifty-two temporal bones, from 38 patients, with the
      histopathologic findings of "endolymphatic hydrops" were analyzed
      microscopically. Data were obtained regarding the displacement of the basilar
      membrane, endolymphatic sac volume, hair cell loss, strial atrophy, ganglion cell
      loss, and last measured auditory thresholds. The relationships between these
      variables were examined statistically. RESULTS: Nineteen of the 52 temporal bones
      (36.5%) with endolymphatic hydrops showed displacement of the basilar membrane
      toward the scala tympani in the apical and middle segments of the cochlea. A
      reduced volume of the endolymphatic sac was significantly related to increased
      severity of basilar membrane deformation (Rho = -.646; P < or = .001). Multiple
      regression analysis showed that severity of basilar membrane deformation was the
      single best predictor of low frequency thresholds while loss of hair cells was
      the best predictor of pure-tone average threshold. CONCLUSIONS: The displacement
      of the basilar membrane in the apical and middle segments that may occur with
      endolymphatic hydrops, to the extent that it impinges on the interscalar septum,
      is related to a reduction in the intraosseous endolymphatic sac volume.

PMID- 15510022
TI  - Sinonasal sarcoidosis: review and report of fifteen cases.
AB  - OBJECTIVES: Sinonasal sarcoidosis remains a poorly understood and uncommon
      chronic granulomatous disease of unclear origin. We have attempted to
      characterize the main clinical and radiologic criteria for diagnosis and to
      discuss the treatment. METHODS: A retrospective study of 15 cases of chronic,
      symptomatic, and biopsy-proven sinonasal sarcoidosis and a review of the
      literature are realized. RESULTS: Among the 15 patients, there were 8 women and 7
      men with a mean age of 44 years. The most frequent presentation was a chronic,
      often crusty, rarely destructive inflammatory rhinosinusitis with nodules on the
      septum and/or the turbinates. Pulmonary sarcoidosis was associated in 12 cases.
      Involvement of the nasopharynx, the pharyngolarynx, the skin, the lachrymal and
      salivary glands, and the liver was associated in some cases. Levels of
      angiotensin-converting enzyme were elevated in 10 cases and normal in 3 cases.
      Gallium scan performed in three cases was positive. Radiologic studies showed
      nodules on the septum and/or the turbinates in 14 cases, complete or subtotal
      opacification of the sinuses and/or the nasal cavities in 13 cases, and
      nasopharyngeal or pharyngolaryngeal lesions in 4 cases. Treatment with
      corticosteroids, methotrexate, azathioprine, and surgery appear globally
      disappointing in view of the side effects and the relapses during a long follow
      up (3-15 yr; mean, 6 yr). CONCLUSION: On the basis of this study, we propose the
      following diagnostic criteria: 1) histopathologic confirmation of noncaseating
      granuloma; 2) chronic rhinosinusitis poorly responsive to conventional treatment
      and radiologic evidence of rhinosinusitis, often with nodules on the septum
      and/or the turbinates; 3) elevated level of angiotensin-converting enzyme; 4)
      positive gallium scan (if performed); 5) frequent evidence of systemic,
      especially pulmonary, sarcoidosis; 6) no evidence of other granulomatous
      diseases, such as Wegener granulomatosis.

PMID- 15510023
TI  - Influence of amphotericin B on the ciliary beat frequency of nasal mucosa.
AB  - OBJECTIVE: A new therapeutic approach in eosinophilic fungal rhinosinusitis is
      topical application of antifungals such as amphotericin B. The tolerability of a
      recently applied concentration of this drug by human nasal mucosa was tested in
      vitro. METHODS: Ciliary beat frequency (CBF) was measured by a photometric
      technique, combining a light microscope, a photometer, a photograph-multiplier,
      and a computed analyzing unit. RESULTS: Treatment for 20 minutes with
      amphotericin B finally diluted in saline to 0.1 mg/mL caused no decrease in CBF.
      By contrast, both amphotericin B diluted in distilled water and distilled water
      without additives lowered CBF about 50%. This decrease was not reversible after
      reincubation for 20 minute in saline. CONCLUSIONS: The results confirm the good
      tolerability of topical amphotericin B in the nasal and paranasal cavity. Because
      of the negative effect of distilled water, final dilution in physiologic solvents
      should be considered.

PMID- 15510024
TI  - Cytokine expression in experimental chronic otitis media with effusion in mice.
AB  - OBJECTIVES: Although otitis media with effusion (OME) is still a common disease
      in children and adults, the pathogenesis is not yet fully understood. We studied
      the effects of intratympanic injection with endotoxin purified from nontypeable
      Haemophilus influenzae on the characteristics of middle ear effusion (MEE).
      METHODS: Murine model of OME was developed by eustachian tube (ET) blockage
      followed by intratympanic inoculation with endotoxin (endotoxin group) or saline
      (control group). The mice were decapitated and histological changes and the
      production of inflammatory cytokines in MEEs were examined 3 days, 2 weeks, and 2
      months after injection. RESULTS: All mice showed OME until 2 months after ET
      blockage. Most MEEs in the control group were serous, and mucoid or pultaceous
      MEEs were found only in the endotoxin group. Subepithelial space of middle ear
      mucosa was severely thickened with the infiltration of a large number of
      mononuclear cells in the endotoxin group. The levels of tumor necrosis factor
      alpha (TNF-alpha) in MEEs were significantly higher in the endotoxin group than
      in the control group at all time points. Further, in situ hybridization showed
      that TNF-alpha messenger RNA was expressed not only by leukocytes and macrophages
      in MEEs but mononuclear cells present in the subepithelial space of middle ear
      mucosa. CONCLUSIONS: These results indicate that ET blockage is essential for the
      induction of serous MEE and additional administration of endotoxin is associated
      with the production of mucoid MEE accompanied by histological changes with
      inflammatory cell infiltration and cytokine production in the tympanic cavity.

PMID- 15510025
TI  - Evaluation of donor site function and morbidity of the fasciocutaneous radial
      forearm flap.
AB  - OBJECTIVE: To assess the results of the use of the free radial forearm flap in
      terms of objective morbidity and subjective patient response. STUDY DESIGN: The
      donor sites were examined from 37 patients who underwent reconstruction with a
      free fasciocutaneous radial forearm flap in the head and neck after ablative
      tumor surgery. METHODS: Patients were asked to fill in a written questionnaire.
      The following additional tests were performed: resting skin temperature of digits
      I and V, temperature after submersion in iced water, grip and pinch tests, and
      goniometry. RESULTS: Resting skin temperature was slightly decreased for donor
      hands 0.69 degrees C (P < .001) and 0.31 degrees C (P = .048) for digits I and V,
      respectively, but recovery after submersion in iced water showed no differences.
      The strength tests and goniometry revealed no statistically significant findings
      between donor and control sides. On the questionnaire, 9 patients (24%) reported
      slightly impaired function, 14 (38%) could not wear their watch or bracelet, 17
      (46%) reported numbness, 5 (14%) reported soreness, 5 (14%) reported itching, 6
      (16%) reported cold intolerance, 5 (14%) reported bad cosmetic appearance, and 9
      (24%) expressed the opinion that they were insufficiently counseled. CONCLUSION:
      There is a negligible objective morbidity of a free radial forearm flap harvest
      procedure, but a number of patients have subjective complaints when asked.
      Elaborate presurgical counseling can probably reduce these complaints.

PMID- 15510026
TI  - Speech intelligibility and quality of life in head and neck cancer survivors.
AB  - OBJECTIVE: Poor speech intelligibility adversely affects quality of life self
      assessment in long term survivors of head and neck cancer treatment. STUDY
      DESIGN: Observational case series including both objective clinical speech
      testing and subjective quality of life questionnaire administration. METHODS:
      Five-year head and neck cancer survivors were recruited to study the association
      between speech intelligibility and quality of life. Survivors were analyzed as an
      entire group, and also subdivided into laryngectomees and non-laryngectomees.
      Objective testing included sentence and word intelligibility. Subjective testing
      included quality of life questionnaires (UWQOL, FACT, FACT-head and neck, and PSS
      HN) and a locally prepared "cancer concern" question. Associations were sought
      between intelligibility, quality of life and demographics. RESULTS: Sixty-two
      survivors underwent testing. Lower sentence intelligibility and word
      intelligibility scores were associated with diminished self-perceived UWQOL
      Speech (P = .0001 and P = .0001, respectively) and PSS-HN Understandability of
      Speech (P = .009 and P = .005). Decreased word intelligibility was additionally
      associated with decreased UWQOL Chewing (P = .003), UWQOL Swallowing (P = .02),
      UWQOL Recreation (P = .05), PSS-HN Willingness to Eat in Public (P = .03), and
      PSS-HN Normalcy of Diet (P = .0001). The associations continued even after
      patients who had undergone laryngectomy were excluded. CONCLUSIONS: Long-term
      survivors of head and neck cancer continue to have both objective and subjective
      deficits in speech parameters five years after treatment. Objective deficits are
      associated with subjective concerns about speech, eating, and recreation.
      Understanding how communication deficits affect quality of life in long-term head
      and neck cancer survivors may allow more effective therapies to modulate these
      concerns in the recovery period.

PMID- 15510027
TI  - Diffuse nasal polyposis and endonasal endoscopic surgery: long-term results, a 65
      case study.
AB  - OBJECTIVE: To analyze the efficacy of a standardized surgical procedure in
      patients with nasal polyposis. STUDY DESIGN: Prospective study of nonrandomized
      cases from a single institution. METHODS: An inception cohort of 65 consecutive
      patients with nasal polyposis observed from January 1994 to December 1997.
      Presence of asthma, allergies, or aspirin intolerance, duration of nasal
      polyposis, previous surgery, and medical treatment were noted. Clinical symptoms
      were evaluated with a visual analogue scale (VAS), and a preoperative computed
      tomography scan was performed before the surgical procedure. At the end of the
      study, an evaluation was performed to collect all information concerning nasal
      symptoms, asthma conditions, quality of life, and patient's opinion about this
      type of surgery. RESULTS: Sixty patients have completed the study. Polyposis was
      isolated in 29 patients (group A), asthma was present in 21 patients (group B),
      and aspirin intolerance in 10 patients (group C). Nasal obstruction (n = 53/60,
      88.3%) and olfactory disturbances (n = 54/56, 96.4%) were the main preoperative
      complaints, according to the VAS, with a high degree of severity. No significant
      difference for nasal symptomatology was found between the three groups. Nasal
      obstruction and olfactory dysfunction was improved in 37 and 42 patients,
      respectively, without a statistical significance between the groups. A reduction
      of the antiasthmatic treatment was observed in 24 of 31 patients. A massive and
      anteriorly localized recurrence was noted in 3 and 19 patients, respectively.
      CONCLUSIONS: Endoscopic sphenoethmoidectomy is indicated for nasal polyposis
      refractory to intensive medical management with a good improvement of patient's
      quality of life.

PMID- 15510028
TI  - Overexpression of ErbB-2 protein in human middle ear cholesteatomas.
AB  - OBJECTIVE: The purpose of this study is to verify the hypothesis that ErbB-2
      protein is overexpressed in human middle ear cholesteatomas and to elucidate the
      relationship between overexpression of ErbB-2 protein, cell proliferation, and
      apoptosis. STUDY DESIGN: Prospective review of 20 patients between 2001 and 2003
      with middle ear cholesteatoma. METHODS: Middle ear cholesteatoma matrix and
      retroauricular skin were immunostained with anti-ErbB-2, Ki-67, and single
      stranded DNA (ssDNA) antibody. The distribution of immunoreactivity to these
      antibodies and labeling indices were compared between cholesteatoma and
      retroauricular skin. RESULTS: In matrix of middle ear cholesteatoma, ErbB-2 and
      ssDNA were expressed in the keratinocytes of all layers and Ki-67 was expressed
      in the keratinocytes of the basal, lower spinous, and occasionally granular
      layer. In retroauricular skin, ErbB-2 and Ki-67 were expressed in the
      keratinocytes of the basal and occasionally lower spinous layer and ssDNA was
      expressed in the keratinocytes of all layers. Labeling indices against anti-ErbB
      2, Ki-67, and ssDNA antibody were significantly greater in cholesteatoma as
      compared with retroauricular skin. CONCLUSIONS: In cases of cholesteatoma, ErbB-2
      protein was overexpressed and cell proliferation and apoptosis of keratinocytes
      were accelerated. ErbB-2 protein could modulate terminal differentiation and
      apoptosis in the keratinocytes of all layers in cholesteatoma matrix and cell
      proliferation in the keratinocytes of the basal and lower spinous layer in normal
      skin.

PMID- 15510029
TI  - Neurologic diagnosis and treatment in patients with computed tomography and nasal
      endoscopy negative facial pain.
AB  - OBJECTIVE: To determine the helpfulness of specialist neurology referral for
      patients with facial pain, a normal sinus computed tomography (CT) scan, and
      normal nasal endoscopy findings. STUDY DESIGN: Prospective identification of
      patients and analysis of data approved by the Institutional Review Board.
      METHODS: The data of 104 consecutive patients presenting with facial pain, a
      normal sinus CT scan, and normal nasal endoscopy findings were reviewed. The
      patients presented to a single rhinologist in a tertiary care institution. All
      patients were referred for specialist neurologic evaluation and potential
      treatment. Further information was obtained from a patient survey. RESULTS: Of
      the 104 patients, 81 were women and 23 were men. The average age was 46 years
      (range, 22-85). Fifty-six had clear CT scans, 48 had minimal change, and all had
      negative endoscopies. Twenty-nine had previous unsuccessful sinus surgery. The
      average follow-up period was 10.5 months. Forty of 75 patients seeing a
      neurologist were seen on multiple occasions. Four percent of patients seen by a
      neurologist had an unsuspected serious intracranial diagnosis. The most common
      diagnoses were migraine (37%), rebound headache (17%), chronic daily headache
      (17%), and obstructive sleep apnea (16%). Overall, 58% improved on medical
      therapy; 60% of those with a clear CT scan improved, and 53% of those with
      minimal change on CT scan improved (P = .749). CONCLUSIONS: Facial pain remains a
      difficult symptom to diagnose and treat in rhinologic practice. Patients often
      undergo surgery without help. Most patients with facial pain, a normal sinus CT
      scan, and normal endoscopy findings benefit from neurologic consultation. Serious
      intracranial pathologic conditions can be excluded and diagnosis-specific
      pharmacogenetic therapy instituted with improvement in more than 50%.

PMID- 15510030
TI  - Image cytometry DNA-analysis of fine needle aspiration cytology to aid
      cytomorphology in the distinction of branchial cleft cyst from cystic metastasis
      of squamous cell carcinoma: a prospective study.
AB  - OBJECTIVE: Frequently, the distinction between branchial cleft cyst and cystic
      metastases from squamous cell carcinoma is difficult by cytomorphology. In a
      prospective study, we investigated the need for, and the value of, image
      cytometry DNA-analysis as a complement to cytologic evaluation of cystic lesions
      in the neck. STUDY DESIGN: Image cytometry DNA-analysis was performed on the fine
      needle aspiration cytology smears from 50 patients, referred to our department,
      with a solitary cystic lesion in the lateral region of the neck. METHODS: Smears
      from aspirates were Giemsa stained and cytologically evaluated. Ahrens image
      analysis was used for DNA analysis on smears stained with Schiff reagent, and
      lymphocytes were used as control cells. Epithelial cells with DNA values
      exceeding 5c were regarded as aneuploid, indicating malignancy. RESULTS: Nine
      lesions were diagnosed as squamous cell cancer metastases cytologically. DNA
      analysis showed aneuploidy in all of them except one. Three of these lesions had
      earlier been diagnosed as branchial cleft cyst at the referring hospital. Eight
      lesions were cytologically inconclusive and four of them were revealed as cystic
      metastasis at histopathologic analysis, and DNA analysis showed aneuploidy in all
      but one, which could not be analyzed. Two of these lesions were also diagnosed as
      branchial cleft cysts at the referring hospital. All benign lesions were diploid.
      Nine lesions were thyroid and salivary gland lesions. CONCLUSION: Image cytometry
      DNA-analysis was shown to help in the distinction between benign and malignant
      cystic lesions. Thus, when conventional cytomorphology does not suffice, DNA
      analysis is clearly a valuable supplement.

PMID- 15510031
TI  - Tissue microarray analysis reveals prognostic significance of COX-2 expression
      for local relapse in T1-2N0 larynx cancer treated with primary radiation therapy.
AB  - OBJECTIVE: The purpose of this analysis is to determine whether a significant
      correlation exists between cyclooxygenase-2 (COX-2) expression and local relapse
      in a large cohort of patients with T1 to 2N0 laryngeal cancer treated with
      primary radiation therapy. METHODS AND MATERIALS: Clinical and molecular analyses
      were conducted on 123 patients with biopsy-proven T1 to 2N0 laryngeal cancer.
      Clinical prognostic factors included pretreatment hemoglobin, age, sex, race, T
      stage, tumor subsite, beam energy, biologically equivalent dose, therapy
      duration, and treatment date. Molecular prognostic factors included COX-2, p53,
      and Ki-67 expression. Expression levels were determined by immunohistochemistry
      on paraffin-embedded tissues arrayed on tissue microarrays. Multivariate analysis
      was done with the Cox proportional hazards model. RESULTS: Thirty-two patients
      have locally relapsed, for an actuarial 5-year local relapse-free rate of 70.4%.
      On multivariate analysis, positive COX-2 expression predicted local relapse after
      radiation therapy. The relative risk (RR) for local relapse with COX-2 positivity
      was 2.57 (95% CI, 1.21-5.47; P = .01). Other prognostic factors for local relapse
      included negative Ki-67 expression (RR = 5.72; 95% CI, 2.04-16.1; P < .001), T2
      stage (RR = 2.98; 95% CI, 1.39-6.38; P = .005), and therapy duration greater than
      43 days (RR = 6.04; 95% CI, 1.37-26.7; P = .02). CONCLUSIONS: Positive COX-2
      expression predicts for local relapse in T1 to 2N0 larynx cancer in a
      multivariate model. This relationship may have potential therapeutic implications
      regarding the use of COX-2 inhibitors during radiation therapy for optimal
      outcome.

PMID- 15510032
TI  - Case report: Cochlear implant magnet migration.
AB  - A 13-month-old cochlear implant recipient underwent routine device activation.
      Three months postoperatively, the patient sustained a fall with contact to the
      area of the implant without immediate complication. Ten months postoperatively,
      the position of the external coil appeared to have moved and the patient did not
      seem to be responding as well to sound. Audiological testing could not elicit
      normal device impedances. AP and lateral plain radiographs of the skull revealed
      migration of the internal magnet from its position within the internal coil to a
      position over the receiver/stimulator. This is the first known published case of
      cochlear implant magnet migration.

PMID- 15510033
TI  - Safe and reliable sound threshold measures with direct vibration of the ossicular
      chain.
AB  - OBJECTIVES: The aim of the study was to evaluate the safety and feasibility of
      piezoelectric malleus vibration audiometer (MVA), which presents micromechanical
      vibrations to the umbo membranae tympani. STUDY DESIGN: Phase I study performed
      in a tertiary referral center (University Hospital). METHODS: The coupling rod of
      the MVA was moved slowly through the outer ear canal toward the eardrum with a
      micromanipulator. Coupling was completed when the rod tip touched the umbo
      membranae tympani. Basic audiologic measures of sound threshold obtained with
      direct stimulation of the malleus are presented. We used MANOVA (multivariate
      repeated measures ANOVA) to investigate the repeatability of MVA thresholds from
      one day to the other and when decoupling and retracting the coupling rod 2 mm off
      the umbo. We also selected the MANOVA to test for unwanted bone-conduction
      threshold shifts after MVA application. We assessed normality of the data by
      quantile-quantile plots of the residuals. RESULTS: Twenty-eight male and 10
      female subjects with normal hearing, 22.2 to 34.6 years old (median age, 27.2 yr)
      underwent an examination. Thirty-six subjects underwent MVA, because 2 of the 38
      subjects who volunteered for the study have not undergone the procedure due to
      the external auditory canal anatomy preventing application of the MVA. The
      results show that it is possible to safely and reliably measure thresholds of
      direct vibration of the ossicular chain. Using pure tone audiograms, no pure tone
      bone- and/or air-conduction threshold shifts occurred after the procedure. None
      of the subjects reported any other ear-related symptoms such as vertigo,
      tinnitus, or dizziness. Geometric mean vibratory displacements at threshold
      ranged from 0.55 nm at 250 Hz to 0.03 nm at 6 kHz. MANOVA demonstrated a
      repeatability of MVA thresholds. CONCLUSION: Malleus vibration audiometry will
      not allow exact linkage of actual implantable hearing aid. But the present study
      demonstrates that MVA can provide an audiometric tool for assessing ossicular
      function and integrity prior to implantation of an electronic hearing amplifier.

PMID- 15510034
TI  - Xylitol enhances bacterial killing in the rabbit maxillary sinus.
AB  - OBJECTIVES: Factors that alter airway surface liquid (ASL) ionic concentrations
      may influence the course of sinusitis. Xylitol has been shown to effect ASL ionic
      composition in vitro and to reduce nasal bacterial carriage, otitis media, and
      dental caries in vivo. We examined the effect of xylitol on experimental
      sinusitis in the rabbit model. STUDY DESIGN: Prospective randomized controlled
      study of xylitol, saline, and Pseudomonas aeruginosa administration to the rabbit
      maxillary sinus. METHODS: P. aeruginosa was administered to the sinuses of 26 New
      Zealand white rabbits. Saline was placed in the left maxillary sinus and xylitol
      in the right. The rabbits were randomly assigned to one of three groups: one,
      simultaneous administration of bacteria and solutions with bacterial analysis at
      20 minutes, 11 rabbits; two, preadministration of solutions 1 hour before
      bacterial infection with analysis at 20 minutes, 11 rabbits; three, established
      sinusitis, 4 rabbits had daily injections of solutions for 5 days starting 7 days
      after P. aeruginosa administration. RESULTS: In group 1, 6.96% of injected
      bacteria were retrieved on the left (saline), whereas 0.095% were retrieved on
      the right (xylitol) (P = .034). In group 2, 5.64% of inoculum was recovered from
      the left and 2.89% from the right (P = .188). Group 3 demonstrated evidence of
      sinusitis with recovery of noninoculate bacteria. with no difference between
      right and left. CONCLUSIONS: Xylitol reduces experimental sinusitis when
      administered simultaneously with bacteria. Its effect in established sinusitis is
      less clear. A role may exist for xylitol in nasal irrigation fluid in human
      disease.

PMID- 15510035
TI  - Methemoglobinemia: early intraoperative detection by clinical observation.
AB  - OBJECTIVES/HYPOTHESIS: Head and neck surgery patients often receive topical
      anesthetics in the office for examination or in the operating room for
      nasotracheal intubation. Benzocaine (a component of many topical preparations) is
      frequently employed for this purpose. Acute methemoglobinemia is a rare but
      potentially lethal complication of benzocaine administration. Early recognition
      and treatment may prevent complications or death. We report a case of acute
      intraoperative methemoglobinemia, caused by benzocaine spray, which was diagnosed
      (and reversed) quickly after the clinical observation of "chocolate brown blood"
      in the surgical field.

PMID- 15510036
TI  - Monitoring tumor recurrence with nasopharyngeal swab and latent membrane protein
      1 and epstein-barr nuclear antigen-1 gene detection in treated patients with
      nasopharyngeal carcinoma.
AB  - OBJECTIVES: Epstein-Barr virus (EBV) is closely related to nasopharyngeal
      carcinoma (NPC). Detection of EBV genomic DNA in a nasopharyngeal swab specimen
      may indicate the presence of NPC, and the EBV genomic DNA is only detected in
      patients with NPC and not in other head and neck cancers. This study aims to
      prove that detection of EBV genomic DNA by means of the latent membrane protein
      (LMP)-1 gene and the Epstein-Barr nuclear antigen (EBNA)-1 gene in the
      nasopharynx in NPC patients after radiation therapy indicates local recurrence of
      NPC. STUDY DESIGN: Prospective. METHODS: Nasopharyngeal swab with polymerase
      chain reaction (PCR)-based LMP-1 and EBNA-1 gene detection was used to monitor
      local recurrence in 84 NPC patients who completed radiation therapy. RESULTS: Of
      the 12 patients demonstrating positive LMP-1 and EBNA-1 gene, 11 had local
      recurrence, and 10 of them had early rT1 mucosal recurrence. Subsequent salvage
      nasopharyngectomy controlled local disease in nine. Only one local recurrence in
      the skull base failed to show LMP-1 gene initially. Detection of LMP-1 gene and
      later verification with EBNA-1 gene from nasopharyngeal swabs in NPC patients
      after radiation therapy predicted local recurrence with a sensitivity of 91.7%
      and a specificity of 98.6%. CONCLUSIONS: Nasopharyngeal swab with LMP-1 and EBNA
      1 gene detection is a useful and reliable method to monitor local recurrence in
      NPC patients. It helps to detect recurrence early and may improve local control
      and enhance survival.

PMID- 15510037
TI  - Superstition and post-tonsillectomy hemorrhage.
AB  - OBJECTIVES/HYPOTHESIS: The objective was to determine whether post-tonsillectomy
      hemorrhages occur more frequently in redheaded children, in patterns of threes,
      on Friday-the-13th days, or with the full moon. STUDY DESIGN: Case-control
      analysis. METHODS: The authors performed multiple statistical analyses of all
      children undergoing tonsillectomy at Temple University Children's Medical Center
      (Philadelphia, PA) during a 29-month period. Children readmitted to the hospital
      with or without surgical control of bleeding were compared with children who did
      not bleed. Relation of post-tonsillectomy hemorrhages to the phase of the moon
      was evaluated using a standard normal deviate. The frequency of surgery performed
      on Friday-the-13th days was compared with a differently dated Friday chosen at
      random. Clusters of three hemorrhages in a 7-day period were recorded. Families
      of children were contacted and asked whether their child had red hair. A chi
      analysis compared redheaded and non-redheaded tonsillectomy patients. RESULTS:
      Twenty-eight of 589 tonsillectomy cases performed required readmission for
      bleeding events. Twenty tonsillectomies occurred on a full-moon day, resulting in
      one bleeding event. One cluster of three post-tonsillectomy hemorrhages occurred
      in a 7-day period. Four of the children who bled had red hair. Two
      tonsillectomies occurred on Friday the 13th, with no associated hemorrhage.
      Statistical analysis revealed a random pattern to post-tonsillectomy hemorrhage.
      CONCLUSION: Post-tonsillectomy hemorrhages do not occur in clusters of three and
      are not more frequent with the full moon or on Friday the 13th. The bleeding rate
      among children with red hair is similar to that of non-redheaded children.

PMID- 15510038
TI  - Facial nerve in parotidectomy: a topographical analysis.
AB  - OBJECTIVE: Establish normative data concerning parotidectomy and facial nerve
      dissection and determine the relationship between the length of the facial nerve
      dissected during parotidectomy and subsequent facial nerve paresis. STUDY DESIGN:
      Prospective mapping of facial nerve during parotidectomy and comparison with
      postoperative facial nerve function. METHODS: A prospective observational study
      of 78 patients who underwent 79 parotidectomy procedures. During each procedure,
      various topographical measurements were recorded. These measurements included the
      distance from the tragal pointer to the main trunk of the facial nerve, the
      distance to the pes anserinus, and length of each segmental branch dissected. In
      addition, a designation of the patient's tumor location was made by drawing a
      line from the ear canal to the nasal spine. Tumors above this line were
      designated anatomic zone A and those below the line were designated anatomic zone
      B. Finally, facial nerve function was quantified at a 1-week follow-up visit
      using the House-Brackmann Scale. RESULTS: The distance from the main trunk of the
      facial nerve to the tragal pointer was significantly (P < .000) less than the
      previously accepted standard of 1 cm. The cervical and marginal mandibular
      branches had more nerve dissected, whereas the eye and forehead branches were the
      least dissected. Results of an independent t test and logistic regression (P =
      .01, both) indicated that patients with temporary facial nerve paresis had a
      significantly greater amount of nerve dissected than patients without temporary
      facial nerve paresis. Patients with short-term facial nerve dysfunction had
      significantly (P < .01) more total nerve dissected (136.73 mm vs. 94.73 mm) than
      patients without short-term facial nerve dysfunction. Patients with nerve
      dissection lengths at the third quartile (130.0 mm) were 3.8 times more likely to
      experience temporary facial nerve paresis than patients with nerve dissection
      lengths at the first quartile (64.5 mm). CONCLUSIONS: The axiom that the main
      trunk of the facial nerve is located 1 cm from the tragal pointer may need to be
      modified to less than 1 cm. The cervical and marginal mandibular branches had
      more nerve dissected, whereas the eye and forehead branches were the least
      dissected. Facial nerve paresis after parotidectomy is associated with the length
      of the facial nerve dissected during the procedure. The greater the length of
      facial nerve dissected, the higher the chance of facial nerve paresis, albeit
      temporarily, in this particular series of patients.

PMID- 15510039
TI  - Albumin-coated tympanostomy tubes: prospective, double-blind clinical study.
AB  - OBJECTIVES: Coating an implant with albumin prevents adhesion of proteins,
      bacteria, and platelets and thus may lead to its improved and prolonged function.
      Previously, we have demonstrated the inhibition of binding of fibronectin, one of
      the most adhesive glycoproteins, on human serum albumin (HSA)-coated tympanostomy
      tubes and the durability of this binding inhibition in a 8-month trial. We have
      also demonstrated that the HSA coating inhibits the binding of Staphylococcus
      aureus and Pseudomonas aeruginosa to titanium plates. This prospective study
      evaluated the effect of albumin coating on tympanostomy tube sequelae and on the
      outcome of tympanostomized patients. STUDY DESIGN: Double-blind, prospective,
      randomized clinical trial. METHODS: Two otolaryngological centers in southern
      Finland enrolled 179 pediatric patients. Number of tube occlusions and otorrhea
      and tube ventilation time in the ears with HSA-coated titanium tympanostomy tubes
      were compared with the contralateral ear with its uncoated, otherwise identical
      titanium tube during a 9-month follow-up period. RESULTS: In HSA-coated tubes,
      average ventilation time was slightly longer and the number of early tube
      occlusions significantly less (P < .05). Moreover, in patients with perioperative
      bleeding, the coating prolonged average ventilation time of tympanostomy tubes
      significantly (P < .05). CONCLUSIONS: HSA coating reduces early tube occlusions
      by preventing adherence of blood and secretion.

PMID- 15510040
TI  - Diathermy smoke extraction in nasal and oropharyngeal surgery.

PMID- 15510041
TI  - Bipedicled sternocleidomastoid muscle flap for reconstruction of tail of parotid
      defects.

PMID- 15510042
TI  - A safe treatment concept for divers with acute inner ear disorders.

PMID- 15510043
TI  - Coronoid-temporalis pedicled rotation flap for orbital floor reconstruction of
      the total maxillectomy defect.
AB  - OBJECTIVES: Total maxillectomy creates a significant defect in the supporting
      framework of the orbit. Successful reconstruction of the deficit requires repair
      of the orbital floor to prevent early and late complications. This paper
      describes the recreation of the orbital floor using a coronoid-temporalis sling.
      STUDY DESIGN: Retrospective review of two patients who underwent total
      maxillectomy and subsequent coronoid-temporalis sling reconstruction of the
      surgical defect. METHODS: The charts of two patients who underwent coronoid
      temporalis reconstruction of the orbital floor were retrospectively reviewed. The
      outcomes were evaluated. The authors present a method for reconstruction of the
      orbital floor and discuss the advantages and disadvantages of this method.
      RESULTS: Two patients underwent successful reconstruction of the orbital floor
      with a coronoid-temporalis sling procedure. Both patients display acceptable
      functional and cosmetic results. CONCLUSION: Coronoid-temporalis sling is a
      readily available and easily modified tissue for reconstruction of the orbital
      floor. It offers similar results to those previously described techniques in this
      area without need for further extensive surgery.

PMID- 15510044
TI  - Temporal artery biopsy: concise guidelines for otolaryngologists.
AB  - Temporal arteritis, also known more accurately as giant cell arteritis (GCA), is
      a multisystem vasculitis of elderly people that involves large and medium-sized
      blood vessels with a particular predilection to the craniofacial branches of the
      carotid arteries, especially the temporal artery. Symptoms include visual loss,
      headaches, fever, audiovestibular symptoms, and jaw claudication.
      Otolaryngologists are consulted to care for these patients to confirm the
      diagnosis, to rule out other causes of face pain and headaches, to care for
      patients with audiovestibular manifestations of GCA, and to perform temporal
      artery biopsies. Consequently, it is important for consultants to understand the
      signs and symptoms and natural history of GCA and the indications, technique, and
      complications of temporal artery biopsy. GCA can appear with protean head and
      neck manifestations. Otolaryngologists should be aware of these and understand
      the issues concerning maximizing the yield from temporal artery biopsies.

PMID- 15510045
TI  - Caution in using subglottic stents for Wegener's granulomatosis.

PMID- 15510051
TI  - Upper airway resistance syndrome--one decade later.
AB  - PURPOSE OF REVIEW: The term upper airway resistance syndrome (UARS) was coined to
      describe a group of patients who did not meet the criteria for diagnosis of
      obstructive apnea-hypopnea syndrome and thus were left untreated. Today, most of
      the patients with UARS remain undiagnosed and are left untreated. RECENT
      FINDINGS: Today, the clinical picture of UARS is better defined. We have learned
      that patients usually seek treatment with a somatic functional syndrome rather
      than sleep-disordered breathing or even a disorder of excessive daytime
      sleepiness. Therefore, most of these patients are seen by psychiatrists. In
      addition, recent technologic advances have allowed a better recognition of the
      problem. We have learned that obstructive apnea-hypopnea syndrome is associated
      with a local neurologic impairment that is responsible for the occurrence of the
      hypopnea and apneas. In contrast, patients with UARS have an intact local
      neurologic system and have the ability to respond to minor changes in upper
      airway dimension and resistance to airflow. New treatment options including
      internal jaw distraction osteogenesis are used and are promising for treatment of
      patients with UARS. SUMMARY: The clinical presentation of patients with UARS is
      similar to the presentation of subjects with functional somatic syndrome. To
      diagnose UARS, nocturnal polysomnography should include additional measurement
      channels.

PMID- 15510052
TI  - Mechanisms of arousal from sleep and their consequences.
AB  - PURPOSE OF REVIEW: In recent years, understanding of the mechanisms by which
      sleep is maintained and the consequences of abnormal arousal from sleep has
      improved rapidly. This review describes the recent insights into the nature of
      sleep and arousal and the particular insights gained in common disease states
      such as sleep-disordered breathing. RECENT FINDINGS: Expansion of the definitions
      of the classic stages of non-REM and REM sleep to include consideration of the
      role of cyclic alternating pattern sleep as a gating mechanism for arousal and
      maintenance of stable sleep has led to a significant advancement in understanding
      the nature of normal and pathologic arousals from sleep. In addition, the effect
      of arousals from sleep on cerebral cortical electrophysiology and autonomic
      activation has been further defined, with a potential effect on clinical
      practice. SUMMARY: Arousal from sleep is dependent on wake-promoting influences
      overwhelming forces promoting sleep. Autonomic activation and cortical arousal
      can significantly affect and destabilize sleep homeostasis. The understanding of
      sleep-respiration interactions continues to evolve. The definition of the minimal
      arousal event is an important research goal. It will be important in clinical
      practice and research to consider sleep stability domains as a complement to
      sleep depth staging to allow better understanding of the relative stability and
      instability of the system and to consider all components of the consequences of
      arousal.

PMID- 15510053
TI  - Neuroendocrine changes in sleep apnea.
AB  - PURPOSE OF REVIEW: To review recent investigations examining the effects of
      neuroendocrine changes in obstructive sleep apnea. RECENT FINDINGS: Gonadal
      hormones have long been implicated in the pathogenesis of obstructive sleep
      apnea. Recently, exogenous testosterone has been shown to exacerbate obstructive
      sleep apnea, whereas hormone replacement therapy in menopausal women may be
      protective in obstructive sleep apnea. Effective treatment of obstructive sleep
      apnea with nasal continuous positive airway pressure has been associated with
      improved insulin sensitivity and testicular function in individuals with
      obstructive sleep apnea. SUMMARY: It is important to consider the potential
      development of sleep apnea in any patient who has an endocrine disorder or is
      receiving certain hormonal therapies. Effective assessment and management of
      obstructive sleep apnea with nasal continuous positive airway pressure may lead
      to a reduction in insulin resistance and hypertension as well as other markers of
      vascular risk in patients with metabolic syndrome.

PMID- 15510054
TI  - Perioperative treatment of patients with obstructive sleep apnea.
AB  - PURPOSE OF REVIEW: Obstructive sleep apnea is a common disorder. Despite reports
      of its role as a risk factor for postoperative morbidity and mortality, only a
      few investigators have examined the optimal treatment of patients during this
      vulnerable period. Recognition of obstructive sleep apnea during conscious
      sedation or in the perioperative period is important to prevent the occurrence of
      adverse outcomes. This review discusses the influence of sedative, anesthetic,
      and analgesic agents and other factors during the perioperative period on
      patients with obstructive sleep apnea. The aim of this article is to emphasize
      the importance of recognizing and appropriately treating surgical patients with
      obstructive sleep apnea. RECENT FINDINGS: Sedative, analgesic, and anesthetic
      agents used perioperatively play a major role in the development of sleep
      disordered breathing during the postoperative period. Postoperative apneic
      episodes frequently occur even after surgery remote from the upper airway. Sleep
      apnea predisposes patients to a greater than normal risk for postsurgical
      complications. Adequate screening of patients preoperatively and initiation of
      continuous positive airway pressure therapy perioperatively could prevent serious
      complications, including hypoxemia, arrhythmias, myocardial infarction, and
      respiratory arrest. SUMMARY: Obstructive sleep apnea places a significant
      proportion of surgical patients at increased risk of perioperative complications.
      Obstructive sleep apnea can be induced, unmasked, or exacerbated by the effects
      of sedative, analgesic, and anesthetic agents regardless of the site of surgery.
      The role of sleep apnea as a risk factor for development of postoperative
      complications needs greater emphasis. Increased awareness of the risk posed by an
      obstructed upper airway and appropriate management are important to optimize the
      perioperative care of patients with obstructive sleep apnea.

PMID- 15510055
TI  - Sleep during mechanical ventilation.
AB  - PURPOSE OF REVIEW: This review addresses the growing interest in the study of
      sleep during critical illness. RECENT FINDINGS: We know that sleep, in all of its
      measurable aspects, is severely deranged in critically ill patients during
      mechanical ventilation. There is growing evidence that mode of mechanical
      ventilation, medications, and acuity of illness may contribute to such sleep
      derangements and that conventional factors such as noise and health care delivery
      may be playing a much smaller role than previously thought. Alternatively,
      changes in sleep-wakefulness state can alter patient-ventilator interaction,
      which may in turn influence physicians' decision-making. Sleep organization may
      predict functional outcome in patients with head trauma. Additionally, there is
      evidence that poor sleep is an important factor influencing long-term quality of
      life in survivors of critical illness. SUMMARY: A more complete understanding of
      the etiopathogenesis of sleep derangements during mechanical ventilation may
      identify new interventions to help improve sleep, and possibly favorably
      influence short-term and long-term outcomes.

PMID- 15510056
TI  - Auto-titrating continuous positive airway pressure for treating adult patients
      with sleep apnea syndrome.
AB  - PURPOSE OF REVIEW: The treatment of sleep apnea syndrome (SAS) is continuous
      positive airway pressure (CPAP) as the first line of therapy. The current
      standard is for an attendant technician to titrate CPAP by means of an in
      laboratory polysomnography to obtain a fixed single pressure. Over the past
      decade and a half, some devices able to modify the pressure delivered to the
      patient overnight and from night to night have become available. The efficacy of
      such devices to manage SAS has been demonstrated, however the question of their
      use either as unattended APAP to determine pressures for fixed CPAP or for self
      adjusting APAP treatment on a long-term basis is still matter of debate. RECENT
      FINDINGS: However, if cost considerations may render reluctant to APAP, off note,
      using APAP could allow initiation of treatment more quickly, reduce in-laboratory
      time, and reduce healthcare costs. SUMMARY: Auto-titrating continuous positive
      airway pressure and CPAP are to date equivalent in terms of efficacy to treat
      SAS, but APAP could allow quick initiation of treatment and therefore reduce
      healthcare costs.

PMID- 15510057
TI  - Update on newborn screening for cystic fibrosis.
AB  - PURPOSE OF REVIEW: Cystic fibrosis (CF) is the most common lethal genetic
      disorder in the United States to be identified in childhood. In November 2003 the
      US Cystic Fibrosis Foundation and the Centers for Disease Control and Prevention
      convened an expert panel to review the indications for CF newborn screening. In
      this review we discuss the information during the year leading up to this meeting
      as well as publications since the meeting. RECENT FINDINGS: During the past
      several years an increasing number of CF patients have been diagnosed with
      newborn screening. These patients have demonstrated several benefits to screening
      while also uncovering new challenges. Health benefits have included improved
      nutrition persisting for many years and the avoidance of nutritional
      complications. Early identification has also meant that these often clinically
      healthy infants are being followed in CF centers for care. This has added to the
      need for avoiding infection risks to which these patients might not have
      otherwise been exposed. Psychosocial benefits include the avoidance of stress due
      to delayed diagnosis as well as assistance with family planning. Psychosocial
      challenges include carrier identification and detection of patients with mild
      disease or without a clear diagnosis. SUMMARY: Although no study has definitively
      shown reduced lung disease or prolonged survival in CF patients detected by
      newborn screening, the general consensus is that improved nutrition and cognitive
      potential, in addition to the reduced costs for hospitalization and intensive
      therapies, support the benefits of screening.

PMID- 15510058
TI  - Association of nutritional status and pulmonary function in children with cystic
      fibrosis.
AB  - PURPOSE OF REVIEW: Multiple studies have shown that nutritional status is a
      strong predictor of morbidity and mortality in patients with cystic fibrosis
      (CF). Since CF is characterized by progressive lung disease, it could be argued
      that the underlying lung disease is what determines the nutritional failure seen
      in most patients. This review will summarize the data available from studies that
      have attempted to better define this relation and also present a review of the
      possible mechanisms involved taken from both observational and interventional
      studies. RECENT FINDINGS: Longitudinal studies with sufficiently large follow-up
      times have demonstrated that young underweight patients have worst pulmonary
      function outcomes. More importantly, these studies concur in that the yearly
      change in growth parameters has a significant effect on the rate at which
      pulmonary function develops. Although the mechanisms behind this important
      association are yet unclear, there is some suggestion from interventional studies
      that the accrual of lean body mass is the factor that is involved in the
      preservation of lung function. SUMMARY: Nutritional status strongly influences
      pulmonary health among CF patients. Therefore, aggressive nutritional support
      aiming at achieving normal growth patterns should lead to adequate development of
      lung function and maintenance of pulmonary health. However, more research is
      required with long-term longitudinal studies to better identify the most critical
      nutritional characteristics influencing this process as well as the most
      effective nutritional interventions.

PMID- 15510059
TI  - Update on cystic fibrosis epidemiology.
AB  - PURPOSE OF REVIEW: With the improving survival of cystic fibrosis (CF) patients,
      the clinical spectrum of this complex multisystem disease continues to evolve.
      Epidemiologic studies have provided important insight into the disease course,
      prognosis, and complications. This review summarizes recent advances in our
      understanding of predictors of survival and outcome and modifiers of disease in
      CF. This review is not meant to be comprehensive, but highlights selected
      studies, many of which have particular relevance to the growing number of older
      CF patients. RECENT FINDINGS: Survival rates of US CF patients improved
      remarkably over the past 15 years, but most of the improvement was limited to
      patients 2 to 15 years of age. Both median household income and ambient air
      pollutants were found to be important modifiers of disease, echoing research
      reported in other chronic lung diseases. Genotype classified according to
      functional mutation class was highly associated with outcome (class I, II, and
      III mutations were associated with the highest mortality). Of the emerging
      pathogens, B. cepacia complex and B. gladioli are the most prominent. A small but
      significant percentage of patients have been shown to acquire new B. cepacia
      complex or B. gladioli strains with time. SUMMARY: Epidemiologic research in
      cystic fibrosis continues to inform patient care and clinical research, and to
      generate new hypotheses regarding pathophysiology. Survival and outcomes continue
      to improve in this multisystem disease. With continued improving survival,
      epidemiologic studies will be critical to tracking changes in prognosis and
      outcome.

PMID- 15510060
TI  - The use of macrolide antibiotics in patients with cystic fibrosis.
AB  - PURPOSE OF REVIEW: There has been much recent interest in the use of macrolide
      antibiotics as chronic suppressive therapy in patients with cystic fibrosis.
      Three recent randomized, placebo-controlled trials have been conducted. RECENT
      FINDINGS: All three trials used similar regimens of azithromycin, and lung
      function improved after 3 to 6 months of treatment. The relative change in forced
      expiratory volume in 1 second predicted improved between 3.6% and 6.2%.
      Furthermore, the azithromycin treatment groups had improvement in a variety of
      secondary outcomes related to pulmonary exacerbations, including a reduction in
      antibiotic use (both intravenous and oral) and hospitalization rate. Furthermore,
      azithromycin was well tolerated: Only nausea, diarrhea, and wheezing (described
      as mild to moderate) occurred more frequently in the azithromycin group compared
      with the placebo group. The evidence for the clinical benefit of azithromycin in
      cystic fibrosis has been summarized in a Cochrane review in which a meta-analysis
      confirmed a significant improvement in forced expiratory volume in 1 second among
      the 286 pooled participants. SUMMARY: Azithromycin has entered the therapeutic
      armamentarium for patients with cystic fibrosis who are chronically infected with
      Pseudomonas aeruginosa. Improved lung function, a reduction in pulmonary
      exacerbations and antibiotic use, and weight gain are potential benefits of this
      drug. Future studies should address the use of azithromycin in other cystic
      fibrosis patient populations, including those patients without chronic infection
      with P. aeruginosa, children younger than 6 years of age, and those infected with
      Burkholderia cepacia complex. The mechanism of action of macrolide antibiotics in
      cystic fibrosis remains unknown.

PMID- 15510061
TI  - Treatment of bone disease in cystic fibrosis.
AB  - PURPOSE OF REVIEW: As individuals with cystic fibrosis (CF) have experienced
      marked improvements in longevity over the last three decades, bone disease has
      emerged as a new problem. Bone disease in CF has not been previously reviewed in
      this journal. Therefore, this review will give a brief overview of bone disease
      in CF and then concentrate on treatment options. RECENT FINDINGS: In some series,
      as many as three fourths of adults with CF have low bone density. Decreased
      absorption of fat-soluble vitamins due to pancreatic insufficiency, altered sex
      hormone production, chronic inflammation, physical inactivity, and glucocorticoid
      treatment are some of the factors that contribute to this problem. Vitamin D
      depletion most likely contributes to bone disease, but identifying the safest and
      most efficacious vitamin D supplementation has yet to be resolved. Calcium and
      vitamin K supplementations are important if the diet contains less than the
      recommended amounts. Treatment of delayed puberty and adult hypogonadism with
      hormone replacement is recommended to achieve peak bone mass and maintain bone
      density. Bisphosphonates, including pamidronate and alendronate, are beneficial
      in improving bone mineral density before and after transplantation in CF adults.
      Bisphosphonates have not been studied in CF children. SUMMARY: Although much
      progress has been made in our understanding of the pathogenesis, natural history,
      and clinical manifestations of bone disease in CF, treatment options are still
      evolving. More attention to nutrition, in terms of the maintenance of lean body
      mass and vitamin D and calcium supplementation, is likely to decrease bone
      complications. Bisphosphonates can be of value in CF adults with low bone
      density. Several clinical trials are under way to help optimize the treatment of
      CF bone disease.

PMID- 15510062
TI  - Potential for antioxidant therapy of cystic fibrosis.
AB  - PURPOSE OF REVIEW: Changes in redox state clearly play a role in airway
      inflammation and mucus rheology. Furthermore CFTR (cystic fibrosis transmembrane
      conductance regulator), the defective protein in cystic fibrosis (CF), not only
      is regulated by redox state but also directly modulates the epithelial redox
      environment through transepithelial flux of glutathione. The purpose of this
      review is to explore the potential therapeutic interest of antioxidant molecules
      in CF. RECENT FINDINGS: Several antioxidants have been shown to have mucolytic
      and anti-inflammatory properties. Some antioxidants such as zinc and vitamin C
      may also help increase epithelial chloride secretion through CFTR-dependent and
      independent pathways. Other antioxidants are showing promise in helping CFTR
      mobilization to plasma membranes. SUMMARY: The many levels of potential
      application offered by antioxidants make this class of molecules one of the
      promising areas of therapeutic development for CF. Several redox-modulating
      agents have a high likelihood of providing useful approaches for the treatment of
      many aspects of CF airway disease.

PMID- 15510063
TI  - High-resolution CT scanning: potential outcome measure.
AB  - PURPOSE OF REVIEW: High-resolution CT (HRCT) imaging of the chest can provide
      both structural and functional lung analysis useful to evaluate initial and
      progressive cystic fibrosis (CF) lung disease. Chest HRCT scoring systems have
      been used to evaluate the extent and severity of CF specific airway and lung
      parenchymal disease. The purpose of this review is to summarize recent
      developments in HRCT and volumetric chest CT imaging, CF chest CT scoring
      systems, and review how HRCT/volumetric CT can provide useful outcome measures
      for future CF clinical research. RECENT FINDINGS: Early manifestation of CF lung
      disease determined by chest CT/HRCT imaging in CF infants and children with mild
      disease include regional air trapping and bronchial wall thickness. The
      distribution of findings in more progressed CF lung disease are heterogeneous,
      and there appears to be a large amount of nonhomogeneity of progressive lung
      pathology. Recent CF studies have used new clinical CT parameters such as
      quantitative air trapping, quantitative airway measurements, and a composite
      CT/pulmonary function test (PFT) score, which appear to be promising new outcome
      measures that are more sensitive than global pulmonary function measurements or
      total chest CT scores in discriminating early or mild CF lung disease and
      treatment effects during clinical interventions. SUMMARY: Chest HRCT and
      volumetric CT imaging can detect regional CF lung changes before changes in
      global pulmonary function measurements. Chest HRCT scoring has been used in
      descriptive studies defining CF lung disease severity, in longitudinal studies to
      define progression of disease, and in clinical intervention studies to evaluate
      treatment effects. In the last 2 years, CF CT research has evolved from solely
      using chest HRCT scoring systems to utilization of composite CT/PFT scores,
      quantitative airway and air trapping measurements, and the utilization of
      volumetric CT imaging to evaluate three-dimensional data sets in patients with CF
      lung disease.

PMID- 15510064
TI  - Advances in cystic fibrosis gene therapy.
AB  - PURPOSE OF REVIEW: The first cystic fibrosis gene therapy trials were carried out
      in 1993, and although proof-of-principle for gene transfer to the lungs was
      established, efficiency was generally low. The authors review the most recent
      advances in preclinical airway gene transfer and summarize the results from the
      latest clinical trials. RECENT FINDINGS: Recent clinical trials report
      encouraging results. Repeat administration of adeno-associated virus to the lung
      was safe. Nonviral nanoparticles used, for the first time, in the nose of cystic
      fibrosis patients were also safe and led to partial correction of the chloride
      transport defect in nasal epithelium. Important advances have been made in
      preclinical research, including the development of new viral and nonviral gene
      transfer agents and improved plasmid DNA. In addition, physical delivery methods,
      such a magnetofection and electroporation, are being assessed to improve nonviral
      gene transfer. SUMMARY: Considerable progress has been made in understanding and
      overcoming the problems associated with gene transfer to airway epithelial cells,
      the target cells for cystic fibrosis gene therapy. It has also been recognized
      that novel preclinical and clinical assays are crucial for the success of cystic
      fibrosis gene therapy, and considerable effort is currently being put into assay
      development and trial designs.

PMID- 15510065
TI  - Pharmacologic therapy for stop mutations: how much CFTR activity is enough?
AB  - PURPOSE OF REVIEW: The purpose of this review is to summarize the recent
      approaches using mutation-specific therapy to correct the genetic defect
      according to the molecular mechanism by which the mutation causes the defects in
      cystic fibrosis transmembrane conductance regulator (CFTR). Premature stop
      mutations (class I mutations) account for 5 to 10% of the total mutant alleles in
      cystic fibrosis patients, and in certain subpopulations the incidence is much
      higher. RECENT FINDINGS: The aminoglycoside antibiotics can suppress premature
      termination codons by permitting translation to continue to the normal
      termination of the transcript. The susceptibility to suppression by
      aminoglycosides depends on the stop codon itself and on the sequence context
      surrounding it. In vitro studies in cell lines expressing stop mutations and in
      mice have shown that aminoglycosides caused a dose-dependent increase in CFTR
      expression and restored functional CFTR to the apical membrane. Clinical studies
      also provided evidence that the aminoglycoside gentamicin can suppress these CFTR
      premature stop mutations in affected patients. A recent double-blind, placebo
      controlled, crossover study has demonstrated restoration of CFTR function by
      topical application of gentamicin to the nasal epithelium of cystic fibrosis
      patients carrying stop mutations. In 21% of the patients there was a complete
      normalization of all the electrophysiologic abnormalities caused by the CFTR
      defect, and in 68% there was restoration of either chloride or sodium transport.
      Furthermore, immunohistochemical staining to the C-terminal part of the CFTR was
      demonstrated via peripheral staining for CFTR in scraped nasal epithelial cells
      of patients carrying stop mutations. Inconsistent results were reported regarding
      the required level of corrected CFTR that has to be reached to achieve normal
      function. Achieving CFTR activity of 10 to 35% might be needed to prevent
      significant pulmonary morbidity. SUMMARY: It is as yet unknown how much corrected
      mutant CFTR must reach the apical membrane to induce a clinically relevant
      beneficial effect. The future goal is to maximize the effect of stop-codon
      supressors on CFTR while minimizing side effects, but further studies must be
      performed to find a safer compound that may be administered in small children
      from the time of diagnosis.

PMID- 15510066
TI  - Bibliography. Current world literature. Sleep and respiratory neurobiology.

PMID- 15510067
TI  - [Hommage to Jean-Pierre Ragot].

PMID- 15510068
TI  - [Exceptions!].

PMID- 15510069
TI  - [Epidermoid carcinoma of oral cavity in patients less than twenty].
AB  - OBJECTIVE: To analyze a review of literature of patients aged less than 20 years
      with epidermoid carcinoma of oral cavity. PATIENTS AND METHODS: Two sources were
      used to identify cases. A Medline search was performed as well as a review of our
      Medlog files where two cases of oral epidermoid carcinoma were identified in
      patients aged less than 20 years. RESULTS: Sixteen patients treated between 1981
      and 2000 were included in this study. The mean age was 15.6 years and the sex
      ratio was 2.2 male/female. The mean time to diagnosis was 16.4 months. Tumors
      were staged III or IV in 71.4% of cases. The mean follow-up was 33.2 months. Rate
      of failure was 50% and one patient experienced local recurrence. At last follow
      up, seven patients were alive with one patient living with cancer. All deaths
      resulted from the original cancer. DISCUSSION: This study illustrates the rarity
      of epidermoid carcinoma of the oral cavity in patients aged less than 20 years.
      Owing to the fact that most tumors were classified III or IV, time to diagnosis
      is probably the most important prognosis factor. Histological examination of all
      lesions of the oral cavity is required, irrespective of the age of the patient.

PMID- 15510070
TI  - [Cicatricial pemphigoid: management in stomatology].
AB  - BACKGROUND: Cicatricial pemphigoid is a subepidermal disease of the mucous
      membranes. In some patients blisters involving the oral cavity may be the only
      manifestation. The purpose of this work was to detail the clinical features and
      biological findings, highlighting the diagnostic and therapeutic difficulties.
      MATERIAL AND METHODS: Seventeen patients, nine women (mean age 59.6 years) and
      eight men (mean age 67.8 years) managed between 1990 and 2000 were reviewed
      retrospectively. RESULTS: Mucous membranes of the mouth were the only
      localization in six of the seventeen patients. Other localizations (skin, eye,
      nose, anus) were associated, alone or in combination, in the other eleven
      patients. The gingivae were involved in 15/17 patients and constituted the only
      localization in six. Skin lesions (sometimes involving the lower limb) were
      variable and found in 6/17 patients. Ocular lesions were present at diagnosis in
      six patients, including two with severe lesions at onset. Nasal and/or laryngeal
      involvement was found in 6/17 patients. These lesions were often severe with
      major functional impact. ENT localizations were found in patients with at least
      three localizations and lesions extending to mucous membranes distant from the
      oral cavity. A biopsy was obtained from all patients and demonstrated
      subepidermal detachment in eleven. Direct immunofluorescence was positive in
      eleven. Indirect immunofluorescence, performed in twelve patients, was negative.
      In two patients, both histology and immunofluorescence were negative. Electron
      immunomicroscopy was performed in four patients and confirmed the diagnosis. Five
      out of six isolated oral manifestations were treated with topical steroids alone.
      Multiple lesions were treated case by case using daprosone and/or systemic
      corticosteroids associated with topical steroids in 16/17 patients. A bolus of
      cyclophosphamid was given for four patients with very severe lesions which did
      not respond to other treatments. At last follow-up (22 +/- 17 months), none of
      the patients was considered cured. DISCUSSION: Cicatricial pemphigoid is a
      complex chronic disease. Oral manifestations may be isolated or associated with
      lesions of the skin or other mucous membranes. The painful aspect of oral lesions
      explains why the diagnosis is often made in stomatology. Careful evaluation at
      diagnosis is essential and requires a multidisciplinary approach. Certain
      diagnosis can be provided by immunohistology, particularly electron
      immunomicroscopy which enables distinguishing cicatricial pemphigoid from other
      autoimmune diseases of the dermo-epidermal junction. Treatment depends on disease
      severity. Isolated oral manifestations are generally well controlled by topical
      corticosteroids which ocular, nasal, and laryngeal localizations often require
      more extensive treatment.

PMID- 15510071
TI  - [Clinicopathological discordance for lesions of the oral mucosa].
AB  - BACKGROUND: The oral cavity is the site of various oral mucosal lesions. The
      physical examination must be completed by a pathology examination in order to
      establish a final diagnosis. The objective of our study was to investigate the
      discordance between clinical and pathological findings concerning lesions oral
      mucosa. MATERIAL AND METHOD: This study was a cross-sectional epidemiological
      investigation involving 21 patients seen during a 16-month period. RESULTS:
      Statistical analysis demonstrated 17 cases of agreement (81%) and 4 cases of
      discordance (19%) between the clinical diagnosis and pathology diagnosis.
      DISCUSSION: Such discordance can be operator-dependent or related to sample
      procurement or handling.

PMID- 15510072
TI  - [Histoplasmosis of the oral cavity].
AB  - Histoplasmosis is an endemic mycosis. Histoplasma capsulatum, and duboisii are
      the pathogenic agents in humans. The disease is reported as endemic in more than
      30 countries. Three clinical forms are distinguished; acute, chronic and
      disseminated. Oral lesions may take on different clinical aspects which are often
      associated with disseminated histoplasmosis. Disseminated histoplasmosis is
      frequently diagnosed in immunocompromised hosts. High risk of mortality dictates
      rapid diagnosis and treatment.

PMID- 15510073
TI  - [Nicardipine-induced gingival hyperplasia: case report].
AB  - Several types of therapeutic agents may induce gingival hyperplasia. An unusual
      case induced by nicardipine, a calcium antagonist, is presented. The other drugs
      concerned are: several anticonvulsants, cyclosporin, and several other calcium
      antagonists. In the majority of patients for whom drug discontinuation or
      substitution is not possible, and for whom prophylactic measures have failed,
      surgical excision of gingival tissue remains the only treatment option.

PMID- 15510074
TI  - [Mandibular ameloblastic fibro-odontoma].
AB  - Ameloblastic fibro-odontoma is a rare and benign tumor. It usually affects young
      patients. This report describes the case of a ten year old child presenting an
      asymptomatic and slow-growing tumor located in the posterior region of the
      mandible. The course was normal and no recurrence was found after simple
      enucleation of the tumor.

PMID- 15510075
TI  - [Pindborg tumor: a poorly differentiated form without calcification].
AB  - BACKGROUND: Pindborg tumor is a rare benign epithelial calcified odontogenic
      tumor. Radiological diagnosis is generally suspected because of the presence of
      calcifications. CASE REPORT: A 61-year-old man presented a polymorphous Pindborg
      tumor of the anterior maxillary. The diagnosis was hindered due to the
      nonspecific radiographic image and the lack of calcification. Pathology provided
      the positive diagnosis of poorly-differentiated young odontogenic epithelial
      tumor. DISCUSSION: Pindborg tumor is a rare lesions usually found in the
      posterior mandibular bone. Calcification is a characteristic feature. There are
      two historical forms, a squamous form with very favorable outcome and a clear
      cell form with less favorable prognosis.

PMID- 15510076
TI  - [Oral antiseptics].

PMID- 15510077
TI  - [Diseases of the oral mucosa. Gingival hypertrophy].

PMID- 15510078
TI  - [Diseases of the oral mucosa. Neuroma].

PMID- 15510083
TI  - Co-detection and discrimination of JCV and BKV DNA by duplex nested-PCR in renal
      transplant recipients.
AB  - AIM: Several studies have disclosed a correlation between human polyomavirus BK
      (BKV) and interstitial nephritis in renal transplant recipients. It has recently
      been hypothesized that some cases of nephropathy may be associated with human
      polyomavirus JC (JCV). METHODS: In this paper we describe the development of
      duplex nested-PCR assay which allows the simultaneous detection and
      discrimination of genomic sequences of JCV and BKV ''large T antigen'', resulting
      in amplicons of 150 bp and 278 bp, respectively. Thus, the presence of JCV and
      BKV DNA in urine and serum samples from 51 renal transplant recipients and 29
      healthy controls was investigated and related to immunosuppressive regimens and
      renal function. RESULTS: The comparison between the incidence of the of BKV
      and/or JCV infections (detected by viruria and/or viraemia) in renal transplant
      recipients and the control group revealed a highly significant increase of the
      incidence of BKV infection in immunosuppressed patients vs healthy subjects
      (62.7% vs 27.6%; p=0.005). In particular, we found a significant increase of BKV
      DNA viruria in renal transplant recipients vs healthy subjects (49% vs 17.2%;
      p=0.01), in agreement with the BKV urinary shedding in renal transplant
      recipients of the literature (5-45%). CONCLUSION: The nested-PCR technique is a
      valid diagnostic tool to detect viral presence in urine and its systemic
      diffusion. Our assay links the high sensitivity of nested amplification with the
      simultaneous detection and discrimination of genomic sequences of JC and BK
      polyomaviruses and thus provides a handy, rapid and sensitive means for DNA
      analysis of large numbers of samples.

PMID- 15510084
TI  - Pro-oxidant activity and methionine metabolism in chronic alcohol abusers:
      relationship to alcohol withdrawal and folate administration.
AB  - AIM: The aim of this study was to investigate whether alcohol withdrawal and
      folate administration could play a role on redox balance and metionine metabolism
      in heavy drinkers. METHODS: The derivatives of reactive oxygen metabolites (d
      ROMs), homocysteine, total thiols, vitamin B12 and folate were evaluated in a
      selected group of 40 consecutive chronic alcohol abusers by comparison with 44
      healthy moderate drinkers, as controls. RESULTS: Before alcohol withdrawal, d
      ROMs were significantly higher (p<0.0001) in heavy drinkers than in controls:
      368.5 (254.8-718.6) U.CARR vs 245 (200.7-360) U.CARR, respectively, median with
      range. Plasma homocysteine were significantly higher in alcoholics than in
      moderate drinkers (p<0.0001): 18 (9.5-82.2) micromol/L vs 9.1 (4.9-19.6)
      micromol/L, respectively. Heavy drinkers also exhibited higher serum thiols than
      moderate drinkers (p<0.003): 605.8 (448.2-717.7) micromol/L vs 554.8 (508.3
      658.4) micromol/L, respectively. The patients showed lower plasma folate than
      controls (p<0.0001): 4.1 (1.9-9.7) ng/mL vs 8.8 (5.0-8.4) ng/mL, respectively,
      but similar vitamin B12 levels: 487 (299-786) pg/mL 621 (243-894) pg/mL. A
      negative correlation between homocysteine and folate was observed before
      withdrawal in alcoholics (r=-0.4546, p<0.038). Both serum thiols (549.7
      micromol/L, range 402.4-616.6 micromol/L) and homocysteinemia (6.6 micromol/L,
      range 2.9-18.5 micromol/L) were significantly decreased (p<0.0001 and p<0.022,
      respectively) after a week of alcohol withdrawal and folate administration.
      CONCLUSION: Our findings show that both enhanced pro-oxidant activity and a
      derangement of methionine metabolism can be observed in heavy drinkers before
      alcohol withdrawal and folate administration. Furthermore, folate seems to be a
      strong determinant of both plasma homocysteine and thiol concentrations.

PMID- 15510085
TI  - Is hepcidin the bridge linking Helicobacter pylori and anemia of chronic
      infection? A research proposal.
AB  - Since the last decade, several studies have reported on the link between chronic
      Helicobacter pylori (H. pylori) or Helicobacter species (H. species) infection
      and a variety of extragastric manifestations, comprising iron-deficiency anemia.
      A crucial question concerns which possible pathogenic mechanism of H. pylori
      infection may be involved in chronic anemia. Recent findings support the
      hypothesis that in subjects with H. pylori-positive gastritis, concomitant
      changes in intragastric pH and ascorbic acid are present that might play a role
      in impairing alimentary iron absorption with consequent sideropenic anemia. It
      has also been speculated that H. pylori infected antrum could act as a
      sequestering focus for iron. The bacterium enhances gastric lactoferrin, which
      captures iron from transferrin. The iron thus bound to lactoferrin is in turn
      picked up by the bacterium, by means of its outer membrane receptors, for its own
      growth. These models, however, are not able to answer why iron-deficiency anemia
      does not develop in all infected subjects. Recently, a new anti-microbial liver
      made peptide, namely hepcidin, has been characterised. The link between hepcidin
      induction, inflammation and anemia both in humans and in animal models supports
      its key role as mediator of anemia of inflammation. In the present paper, we
      highlight the data available on the association between H. pylori and iron
      deficiency anemia and, we propose to evaluate a possible mechanism involving
      hepcidin in a bridging role linking the infection to the anemia.

PMID- 15510086
TI  - Progressive liver injury in chronic hepatitis C infection is related to altered
      cellular immune response and to different citokine profile.
AB  - Natural immune responses, both cellular and humoral, are not capable of
      terminating HCV infection in most patients. The aim of this study was to
      evaluate: a) the importance of the immune system in the pathogenesis of chronic
      HCV infection; b) analysis of successful immunoresponses in persons infected with
      C virus; c) immuno mechanisms in the progression of hepatic damage; d) different
      cytokine profiles from patients with persistent and self-limited hepatitis C
      virus infection; e) development of new antiviral strategies when virus is
      resistant to interferon treatment. The inadequate T helper1 (Th1) immunity as
      well as the weak HCV-specific T-cell response at the site of inflammation is
      associated with failure to clear the virus and a chronic course of disease. The
      production of interleukin 12 (IL-12) is critical for induction of Th1 immunity,
      directed towards elimination of intracellular pathogenes and viruses. The core
      protein of HCV seems to have a suppressive action on IL-12 production at the
      transcriptional level. The specific Th1 cell defect is correlated with
      insufficient Th and CTL responses, and lower production of type 1 cytokine (IL-2,
      IFN-gamma, lymphokine-activated killer cells). Taken together, these results are
      probably responsible for non-eradication of HCV infection. Particularly the
      effects of interferon-gamma may include inhibition of HCV virion production by an
      effect on viral RNA and protein synthesis, enhancement of immune lysis of HCV
      infected cells, inhibition of hepatic fibrosis by an effect on TGF-beta, and an
      effect on HCV induced carcinogenesis. These data suggest an HCV-related cellular
      immune defect in patients with hepatitis C that can be restored in most patients
      by IL-12. New approaches using a combination of nucleoside analogs or other
      strategies, such as immune intervention (DNA vaccine, stimulation of the Th1
      response) or gene therapy (antisense oligonucleotides dominant negative mutants)
      should therefore be evaluated in animal models to optimize the current antiviral
      protocols.

PMID- 15510087
TI  - Psychological treatment of eating disorders. A review of the literature.
AB  - The aim of this study is to review the existing literature (PubMed database) on
      the psychological treatments for eating disorders (EDs), subdivided in
      individual, group and family therapies. Moreover new approaches and directions in
      this field are addressed. An extensive literature review is performed to identify
      the psychological treatment trials in anorexia nervosa (AN) and bulimia nervosa
      (BN) published over the past 2 decades. Eighty-two studies focused on
      psychotherapeutic treatment of EDs are reviewed. Only a minor part of these
      studies are randomised and controlled. While there is evidence of the efficacy of
      cognitive behavioral therapy (CBT), this is still missing for other
      psychotherapeutic approaches. However, there is general agreement about the
      importance of psychotherapy in multimodal treatments. There is still a need for a
      shared concept of outcome in EDs, since the efficacy of psychological treatment
      is greatly influenced by the definition of outcome adopted (concerning symptoms,
      psychosocial functioning, personality).

PMID- 15510088
TI  - Spinal cord stimulation in neuropathic pain of the lower limbs in a patient with
      Behcet's disease and permanent cardiac DDD pacing.

PMID- 15510089
TI  - Acquired post partum hemophilia.

PMID- 15510090
TI  - A brief history of the anteroposterior open-mouth radiograph.
AB  - OBJECTIVE: To describe the origins of the anteroposterior (AP) open-mouth
      radiograph. METHODS: Searches in PubMed, standard radiography texts, and
      telephone interviews. RESULTS: The AP open-mouth radiograph has a long history of
      use in the chiropractic and medical professions. The view is taken to assess the
      upper cervical vertebrae (C1 and C2), and some chiropractors include assessment
      of the atlantooccipital articulation by using the AP open-mouth radiograph
      procedure. One text cited a 1910 background reference for this view, but further
      investigation revealed an earlier edition of the 1910 publication, which gave a
      description of how to take an AP open-mouth radiograph. The first documentation
      that this view had been taken was found in a 1919 chiropractic text.
      Chiropractors appear to have been the first to include an atlantooccipital
      biomechanical analysis with the AP open-mouth radiograph. CONCLUSION: The origins
      of the AP open-mouth radiograph date back to the early 1900s. A medical doctor in
      Germany appears to have been the first to describe the procedure for this
      radiographic view. By the 1930s, chiropractors were including the occiput in the
      view's analysis, along with the traditional application of C1 and C2 assessment.

PMID- 15510091
TI  - Cervical kyphosis is a possible link to attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: To discuss the case of a patient who was diagnosed with attention
      deficit/hyperactivity disorder (ADHD) by a general practitioner and was treated
      with chiropractic care. CLINICAL FEATURES: A 5-year-old patient was diagnosed
      with ADHD and treated by a pediatrician unsuccessfully with methylphenidate
      (Ritalin), Adderall, and Haldol for 3 years. The patient received 35 chiropractic
      treatments during the course of 8 weeks. A change from a 12 degrees C2-7 kyphosis
      to a 32 degrees C2-7 lordosis was observed after treatment. During chiropractic
      care, the child's facial tics resolved and his behavior vastly improved. After 27
      chiropractic visits, the child's pediatrician stated that the child no longer
      exhibited symptoms of ADHD. The changes in structure and function may be related
      to the correction of cervical kyphosis. CONCLUSION: The patient experienced
      significant reduction in symptoms. Additionally, the medical doctor concluded
      that the reduction in symptoms was significant enough to discontinue the
      medication. There may be a possible connection that correction of cervical
      kyphosis in patients with ADHD may produce a desirable clinical outcome.

PMID- 15510092
TI  - The nordic back pain subpopulation program: demographic and clinical predictors
      for outcome in patients receiving chiropractic treatment for persistent low back
      pain.
AB  - OBJECTIVE: To identify demographic and clinic-related predictors for successful
      outcome in patients with persistent low-back pain who received chiropractic
      treatment. DESIGN: Prospective uncontrolled multicenter study with internal
      control groups. SUBJECTS: Each of 115 Norwegian chiropractors, out of 205
      invited, were asked to recruit 10 consecutive patients who had low-back pain for
      at least 2 weeks at the time of consultation and a minimum of 30 days altogether
      within the preceding year. In all, 875 patients were included at baseline. The
      response rates at the fourth visit and at 3 and 12 months were 799, 598, and 512,
      respectively. METHODS: Baseline data were obtained through questionnaires
      administered to chiropractic patients and to their treating chiropractors;
      clinical information was obtained through questionnaires at the fourth visit from
      patients and chiropractors. Outcome was obtained from patients at the fourth
      visit. Mail surveys of patients were conducted after 3 and 12 months, and
      additional information was obtained from chiropractors at 12 months in relation
      to treatment history. POTENTIAL PREDICTORS: Demography and information on past
      and present history, clinical findings, and prognosis. OUTCOME VARIABLE: Number
      of low-back pain"free patients (defined as those with a maximum pain score of
      1/10 and a maximum Oswestry score of 15/100). DATA ANALYSIS: Positive predictive
      values and relative risks were calculated for each categorized predictor variable
      singly and in combination in relation to being low-back pain free at the 3 follow
      up surveys. RESULTS: Treatment outcome at the fourth visit was best predicted by
      a model containing the following 5 variables: sex, social benefit, severity of
      pain, duration of continuous pain at first consultation, and additional neck pain
      (odds ratios between 2.2 and 4.3). A similar profile was found at 3 months, but 2
      different variables (relating to disability) were the final variables in relation
      to the 12-month status. These final models were best at predicting absence of
      treatment success. Being low-back pain free at the fourth visit was a strong
      predictor for being low-back pain free both at 3 months and 12 months, with
      relative risks of 3.0 (2.2-4.8) and 3.1 (1.5-6.5), respectively. CONCLUSION: In
      patients with persistent low-back pain, it is possible to exclude from treatment
      those who are unlikely to become low-back pain free after chiropractic care and
      to do this before they have been examined clinically. Early recovery is a strong
      predictor for outcome up to 1 year later.

PMID- 15510093
TI  - Spinal manipulation, epidural injections, and self-care for sciatica: a pilot
      study for a randomized clinical trial.
AB  - OBJECTIVE: To assess the feasibility of recruiting sciatica patients and to
      evaluate their compliance in preparation for a full-scale randomized clinical
      trial. We also aimed to determine the responsiveness of key outcome measures.
      METHODS: Thirty-two subjects were randomly assigned to spinal manipulation
      (n=11), epidural steroid injections (n=11), or self-care education (n=10). No
      between-group comparisons were planned because of the small sample size. RESULTS:
      At week 12 (the end of the treatment phase), the outcome measures indicating the
      most improvement/change were the Oswestry disability score (mean, 22.9; SD, 19.9;
      effect size [ES], 1.8), leg pain severity (mean, 2.9; SD, 1.7; ES, 1.7), and if
      the symptoms were bothersome (mean, 25.2; SD, 16.0; ES, 1.6). Twenty-four
      patients were either "very satisfied" or "completely satisfied," and 22 of 32
      patients reported 75% or 100% improvement. After 52 weeks, the outcome measure
      showing the most improvement/change was leg pain severity (mean, 2.3; SD, 2.6;
      ES, 1.35), followed by the Oswestry disability score (mean, 15.6; SD, 20; ES,
      1.2) and if symptoms were bothersome (mean, 18.1; SD, 22.6; ES, 1.1). Eighteen
      patients were either "very satisfied" or "completely satisfied," and 15 of 32
      patients reported 75% or 100% improvement. CONCLUSIONS: The results of this pilot
      study suggest that it is feasible to recruit subacute and chronic sciatica
      patients and to obtain their compliance for a full-scale randomized clinical.

PMID- 15510094
TI  - Efficacy of preventive spinal manipulation for chronic low-back pain and related
      disabilities: a preliminary study.
AB  - OBJECTIVE: To document the potential role of maintenance chiropractic spinal
      manipulation to reduce overall pain and disability levels associated with chronic
      low-back conditions after an initial phase of intensive chiropractic treatments.
      METHODS: Thirty patients with chronic nonspecific low-back pain were separated
      into 2 groups. The first group received 12 treatments in an intensive 1-month
      period but received no treatment in a subsequent 9-month period. For this group,
      a 4-week period preceding the initial phase of treatment was used as a control
      period to examine the sole effect of time on pain and disability levels. The
      second group received 12 treatments in an intensive 1-month period and also
      received maintenance spinal manipulation every 3 weeks for a 9-month follow-up
      period. Pain and disability levels were evaluated with a visual analog scale and
      a modified Oswestry questionnaire, respectively. RESULTS: The 1-month control
      period did not modify the pain and disability levels. For both groups, the pain
      and disability levels decreased after the intensive phase of treatments. Both
      groups maintained their pain scores at levels similar to the postintensive
      treatments throughout the follow-up period. For the disability scores, however,
      only the group that was given spinal manipulations during the follow-up period
      maintained their postintensive treatment scores. The disability scores of the
      other group went back to their pretreatment levels. CONCLUSIONS: Intensive spinal
      manipulation is effective for the treatment of chronic low back pain. This
      experiment suggests that maintenance spinal manipulations after intensive
      manipulative care may be beneficial to patients to maintain subjective
      postintensive treatment disability levels. Future studies, however, are needed to
      confirm the finding in a larger group of patients with chronic low-back pain.

PMID- 15510095
TI  - Hamate hook fracture in a 17-year-old golfer: importance of matching symptoms to
      clinical evidence.
AB  - OBJECTIVE: To describe the importance of correlating symptoms with objective
      clinical findings and appropriate diagnostic imaging in a patient with traumatic
      wrist pain. CLINICAL FEATURES: A 17-year-old golfer had persistent left wrist
      pain of 4 months' duration that began while playing golf. Approximately 1 week
      after injury, he was diagnosed with a scaphoid fracture and was splinted. He
      reported that his pain did not decrease with splinting or with subsequent
      physical therapy, and on dismissal from orthopedic care he could not use the
      wrist well enough to return to golf. INTERVENTION AND OUTCOME: The patient was
      found to have marked point tenderness at the hamate. Although plain-film
      radiography was negative, secondary computed tomography of the wrist showed a
      fracture to the hook of the hamate. A referral was made to an orthopedic surgeon
      and surgical excision of the hook of the hamate was recommended because of the
      failure of union at the fracture site. CONCLUSION: This case shows the
      significance of follow-up diagnostic imaging in a patient who does not respond as
      expected. In addition, it stresses the importance of the doctor of chiropractic
      in the diagnostic process, although the patient may have been treated and
      released by another physician.

PMID- 15510096
TI  - Postsurgical rehabilitative management of avascular necrosis in the capitate.
AB  - OBJECTIVE: To discuss a case of avascular necrosis of the capitate and the follow
      up postsurgical rehabilitation. CLINICAL FEATURES: A 41-year-old woman had severe
      left wrist pain. A short course of passive therapy was administered with no
      significant change. She was referred for additional diagnostic testing, including
      magnetic resonance imaging, which assisted in diagnosing the patient with
      avascular necrosis of the capitate. After undergoing surgical intervention, she
      was cleared to start an active rehabilitation program. She had significant loss
      of muscle strength and muscle atrophy and diminished active range of motion in
      the wrist and forearm. INTERACTION AND OUTCOME: The patient underwent surgical
      intervention consisting of an arthroplasty to the capitate. The follow-up
      rehabilitation techniques included the use of active and passive stretching,
      therapeutic putty, and light dumbbells. The patient was seen a total of 21 times
      during a 9-week time period. Outcome assessments were given intermittently during
      care to monitor progress. At the end of the program, she reported full function
      of the wrist with minimal to no pain. A 6-month follow-up showed improvements
      that were maintained with little pain. CONCLUSION: Avascular necrosis of the
      capitate is relatively rare. Advanced imaging should be used for diagnostic
      purposes. Surgical intervention may be warranted; however, it is recommended a
      postsurgical rehabilitative procedure be implemented.

PMID- 15510097
TI  - Flaws in a recent vertebral artery dissection study by Smith et al.

PMID- 15510098
TI  - The reliability of quantifying upright standing postures as a baseline diagnostic
      clinical tool.

PMID- 15510099
TI  - Spontaneous cervical artery dissections and implications for homocysteine.

PMID- 15510101
TI  - The unexamined population.

PMID- 15510100
TI  - 'Race' and the human genome.

PMID- 15510103
TI  - Auditory brainstem response detects early bilirubin neurotoxicity at low indirect
      bilirubin values.
AB  - When sedation, prematurity or other disease processes mask symptoms in the
      clinically ill newborn, serum bilirubin concentration is monitored as the sole
      indicator of kernicterus risk. This case emphasizes the value of auditory
      brainstem responses for the management of indirect hyperbilirubinemia complicated
      by prematurity, hemolytic anemia, asphyxia, and direct hyperbilirubinemia.

PMID- 15510102
TI  - Forensic genetics and ethical, legal and social implications beyond the clinic.
AB  - Data on human genetic variation help scientists to understand human origins,
      susceptibility to illness and genetic causes of disease. Destructive episodes in
      the history of genetic research make it crucial to consider the ethical and
      social implications of research in genomics, especially human genetic variation.
      The analysis of ethical, legal and social implications should be integrated into
      genetic research, with the participation of scientists who can anticipate and
      monitor the full range of possible applications of the research from the earliest
      stages. The design and implementation of research directs the ways in which its
      results can be used, and data and technology, rather than ethical considerations
      or social needs, drive the use of science in unintended ways. Here we examine
      forensic genetics and argue that all geneticists should anticipate the ethical
      and social issues associated with nonmedical applications of genetic variation
      research.

PMID- 15510104
TI  - Distal arthrogryposis and neonatal hypotonia: an unusual presentation of Prader
      Willi syndrome (PWS).
AB  - The clinical features of Prader-Willi Syndrome (PWS) in the neonate are marked by
      hypotonia, absence of crying, and feeding difficulties, but the clinical nature
      of PWS in utero remains unclear. We report a case of PWS with fetal immobility
      and distal arthrogryposis in a girl admitted the first day of life to the
      neonatal intensive care unit for severe hypotonia and respiratory distress.

PMID- 15510106
TI  - Fishing for excuses.

PMID- 15510105
TI  - The netrin receptor UNC5B mediates guidance events controlling morphogenesis of
      the vascular system.
AB  - Blood vessels and nerves are complex, branched structures that share a high
      degree of anatomical similarity. Guidance of vessels and nerves has to be
      exquisitely regulated to ensure proper wiring of both systems. Several regulators
      of axon guidance have been identified and some of these are also expressed in
      endothelial cells; however, the extent to which their guidance functions are
      conserved in the vascular system is still incompletely understood. We show here
      that the repulsive netrin receptor UNC5B is expressed by endothelial tip cells of
      the vascular system. Disruption of the Unc5b gene in mice, or of Unc5b or netrin
      1a in zebrafish, leads to aberrant extension of endothelial tip cell filopodia,
      excessive vessel branching and abnormal navigation. Netrin-1 causes endothelial
      filopodial retraction, but only when UNC5B is present. Thus, UNC5B functions as a
      repulsive netrin receptor in endothelial cells controlling morphogenesis of the
      vascular system.

PMID- 15510107
TI  - Struggling with the flu.

PMID- 15510108
TI  - Science shares the limelight as election battle enters final phase.

PMID- 15510109
TI  - Geneticists struggle towards consensus on place for 'race'.

PMID- 15510110
TI  - Ultrasound scans accused of disrupting brain development.

PMID- 15510111
TI  - Spain's budget fails basic science, researchers charge.

PMID- 15510112
TI  - Comet impact theory faces repeat analysis.

PMID- 15510113
TI  - Generic drugs allowed in global trial of AIDS therapy.

PMID- 15510114
TI  - Deluge of typhoons may aid forecast models.

PMID- 15510115
TI  - Novartis goes public with DNA data in bid to tackle diabetes.

PMID- 15510116
TI  - Little lady of Flores forces rethink of human evolution.

PMID- 15510119
TI  - Astronomy: bagging bursts, swiftly.

PMID- 15510118
TI  - Earthquake prediction: a seismic shift in thinking.

PMID- 15510120
TI  - Knowledge is a good base to campaign from.

PMID- 15510121
TI  - Why leave it to others to speak up about science?

PMID- 15510122
TI  - Scientists must conquer reluctance to speak out.

PMID- 15510128
TI  - A wake-up call.

PMID- 15510129
TI  - Palaeoanthropology: human evolution writ small.

PMID- 15510130
TI  - Astronomy: Tycho's mystery companion.

PMID- 15510132
TI  - Conservation biology: biodiversity barometers.

PMID- 15510133
TI  - Molecular motors: smooth coupling in Salmonella.

PMID- 15510134
TI  - Solar physics: spots from rings.

PMID- 15510135
TI  - Evolutionary biology: mortality and lifespan.

PMID- 15510138
TI  - Phylogeography: English elm is a 2,000-year-old Roman clone.
AB  - The outbreak of Dutch elm disease in the 1970s ravaged European elm populations,
      killing more than 25 million trees in Britain alone; the greatest impact was on
      Ulmus procera, otherwise known as the English elm. Here we use molecular and
      historical information to show that this elm derives from a single clone that the
      Romans transported from Italy to the Iberian peninsula, and from there to
      Britain, for the purpose of supporting and training vines. Its highly efficient
      vegetative reproduction and its inability to set seeds have preserved this clone
      unaltered for 2,000 years as the core of the English elm population--and the
      preponderance of this susceptible variety may have favoured a rapid spread of the
      disease.

PMID- 15510139
TI  - Structure of the bacterial flagellar hook and implication for the molecular
      universal joint mechanism.
AB  - The bacterial flagellum is a motile organelle, and the flagellar hook is a short,
      highly curved tubular structure that connects the flagellar motor to the long
      filament acting as a helical propeller. The hook is made of about 120 copies of a
      single protein, FlgE, and its function as a nano-sized universal joint is
      essential for dynamic and efficient bacterial motility and taxis. It transmits
      the motor torque to the helical propeller over a wide range of its orientation
      for swimming and tumbling. Here we report a partial atomic model of the hook
      obtained by X-ray crystallography of FlgE31, a major proteolytic fragment of FlgE
      lacking unfolded terminal regions, and by electron cryomicroscopy and three
      dimensional helical image reconstruction of the hook. The model reveals the
      intricate molecular interactions and a plausible switching mechanism for the hook
      to be flexible in bending but rigid against twisting for its universal joint
      function.

PMID- 15510140
TI  - The binary progenitor of Tycho Brahe's 1572 supernova.
AB  - The brightness of type Ia supernovae, and their homogeneity as a class, makes
      them powerful tools in cosmology, yet little is known about the progenitor
      systems of these explosions. They are thought to arise when a white dwarf
      accretes matter from a companion star, is compressed and undergoes a
      thermonuclear explosion. Unless the companion star is another white dwarf (in
      which case it should be destroyed by the mass-transfer process itself), it should
      survive and show distinguishing properties. Tycho's supernova is one of only two
      type Ia supernovae observed in our Galaxy, and so provides an opportunity to
      address observationally the identification of the surviving companion. Here we
      report a survey of the central region of its remnant, around the position of the
      explosion, which excludes red giants as the mass donor of the exploding white
      dwarf. We found a type G0-G2 star, similar to our Sun in surface temperature and
      luminosity (but lower surface gravity), moving at more than three times the mean
      velocity of the stars at that distance, which appears to be the surviving
      companion of the supernova.

PMID- 15510141
TI  - Recent ice-rich deposits formed at high latitudes on Mars by sublimation of
      unstable equatorial ice during low obliquity.
AB  - Observations from the gamma-ray spectrometer instrument suite on the Mars Odyssey
      spacecraft have been interpreted as indicating the presence of vast reservoirs of
      near-surface ice in high latitudes of both martian hemispheres. Ice
      concentrations are estimated to range from 70 per cent at 60 degrees latitude to
      100 per cent near the poles, possibly overlain by a few centimetres of ice-free
      material in most places. This result is supported by morphological evidence of
      metres-thick layered deposits that are rich in water-ice and periglacial-like
      features found only at high latitudes. Diffusive exchange of water between the
      pore space of the regolith and the atmosphere has been proposed to explain this
      distribution, but such a degree of concentration is difficult to accommodate with
      such processes. Alternatively, there are suggestions that ice-rich deposits form
      by transport of ice from polar reservoirs and direct redeposition in high
      latitudes during periods of higher obliquity, but these results have been
      difficult to reproduce with other models. Here we propose instead that, during
      periods of low obliquity (less than 25 degrees), high-latitude ice deposits form
      in both hemispheres by direct deposition of ice, as a result of sublimation from
      an equatorial ice reservoir that formed earlier, during a prolonged high
      obliquity excursion. Using the ice accumulation rates estimated from global
      climate model simulations we show that, over the past ten million years, large
      variations of Mars' obliquity have allowed the formation of such metres-thick,
      sedimentary layered deposits in high latitude and polar regions.

PMID- 15510142
TI  - Continuous generation of single photons with controlled waveform in an ion-trap
      cavity system.
AB  - The controlled production of single photons is of fundamental and practical
      interest; they represent the lowest excited quantum states of the radiation
      field, and have applications in quantum cryptography and quantum information
      processing. Common approaches use the fluorescence of single ions, single
      molecules, colour centres and semiconductor quantum dots. However, the lack of
      control over such irreversible emission processes precludes the use of these
      sources in applications (such as quantum networks) that require coherent exchange
      of quantum states between atoms and photons. The necessary control may be
      achieved in principle in cavity quantum electrodynamics. Although this approach
      has been used for the production of single photons from atoms, such experiments
      are compromised by limited trapping times, fluctuating atom-field coupling and
      multi-atom effects. Here we demonstrate a single-photon source based on a
      strongly localized single ion in an optical cavity. The ion is optimally coupled
      to a well-defined field mode, resulting in the generation of single-photon pulses
      with precisely defined shape and timing. We have confirmed the suppression of two
      photon events up to the limit imposed by fluctuations in the rate of detector
      dark counts. The stream of emitted photons is uninterrupted over the storage time
      of the ion, as demonstrated by a measurement of photon correlations over 90 min.

PMID- 15510143
TI  - Crystallization of charge holes in the spin ladder of Sr14Cu24O41.
AB  - Determining the nature of the electronic phases that compete with
      superconductivity in high-transition-temperature (high-T(c)) superconductors is
      one of the deepest problems in condensed matter physics. One candidate is the
      'stripe' phase, in which the charge carriers (holes) condense into rivers of
      charge that separate regions of antiferromagnetism. A related but lesser known
      system is the 'spin ladder', which consists of two coupled chains of magnetic
      ions forming an array of rungs. A doped ladder can be thought of as a high-T(c)
      material with lower dimensionality, and has been predicted to exhibit both
      superconductivity and an insulating 'hole crystal' phase in which the carriers
      are localized through many-body interactions. The competition between the two
      resembles that believed to operate between stripes and superconductivity in high
      T(c) materials. Here we report the existence of a hole crystal in the doped spin
      ladder of Sr14Cu24O41 using a resonant X-ray scattering technique. This phase
      exists without a detectable distortion in the structural lattice, indicating that
      it arises from many-body electronic effects. Our measurements confirm theoretical
      predictions, and support the picture that proximity to charge ordered states is a
      general property of superconductivity in copper oxides.

PMID- 15510144
TI  - All-optical control of light on a silicon chip.
AB  - Photonic circuits, in which beams of light redirect the flow of other beams of
      light, are a long-standing goal for developing highly integrated optical
      communication components. Furthermore, it is highly desirable to use silicon--the
      dominant material in the microelectronic industry--as the platform for such
      circuits. Photonic structures that bend, split, couple and filter light have
      recently been demonstrated in silicon, but the flow of light in these structures
      is predetermined and cannot be readily modulated during operation. All-optical
      switches and modulators have been demonstrated with III-V compound
      semiconductors, but achieving the same in silicon is challenging owing to its
      relatively weak nonlinear optical properties. Indeed, all-optical switching in
      silicon has only been achieved by using extremely high powers in large or non
      planar structures, where the modulated light is propagating out-of-plane. Such
      high powers, large dimensions and non-planar geometries are inappropriate for
      effective on-chip integration. Here we present the experimental demonstration of
      fast all-optical switching on silicon using highly light-confining structures to
      enhance the sensitivity of light to small changes in refractive index. The
      transmission of the structure can be modulated by up to 94% in less than 500 ps
      using light pulses with energies as low as 25 pJ. These results confirm the
      recent theoretical prediction of efficient optical switching in silicon using
      resonant structures.

PMID- 15510145
TI  - Unusual activity of the Sun during recent decades compared to the previous 11,000
      years.
AB  - Direct observations of sunspot numbers are available for the past four centuries,
      but longer time series are required, for example, for the identification of a
      possible solar influence on climate and for testing models of the solar dynamo.
      Here we report a reconstruction of the sunspot number covering the past 11,400
      years, based on dendrochronologically dated radiocarbon concentrations. We
      combine physics-based models for each of the processes connecting the radiocarbon
      concentration with sunspot number. According to our reconstruction, the level of
      solar activity during the past 70 years is exceptional, and the previous period
      of equally high activity occurred more than 8,000 years ago. We find that during
      the past 11,400 years the Sun spent only of the order of 10% of the time at a
      similarly high level of magnetic activity and almost all of the earlier high
      activity periods were shorter than the present episode. Although the rarity of
      the current episode of high average sunspot numbers may indicate that the Sun has
      contributed to the unusual climate change during the twentieth century, we point
      out that solar variability is unlikely to have been the dominant cause of the
      strong warming during the past three decades.

PMID- 15510146
TI  - Archaeology and age of a new hominin from Flores in eastern Indonesia.
AB  - Excavations at Liang Bua, a large limestone cave on the island of Flores in
      eastern Indonesia, have yielded evidence for a population of tiny hominins,
      sufficiently distinct anatomically to be assigned to a new species, Homo
      floresiensis. The finds comprise the cranial and some post-cranial remains of one
      individual, as well as a premolar from another individual in older deposits. Here
      we describe their context, implications and the remaining archaeological
      uncertainties. Dating by radiocarbon (14C), luminescence, uranium-series and
      electron spin resonance (ESR) methods indicates that H. floresiensis existed from
      before 38,000 years ago (kyr) until at least 18 kyr. Associated deposits contain
      stone artefacts and animal remains, including Komodo dragon and an endemic,
      dwarfed species of Stegodon. H. floresiensis originated from an early dispersal
      of Homo erectus (including specimens referred to as Homo ergaster and Homo
      georgicus) that reached Flores, and then survived on this island refuge until
      relatively recently. It overlapped significantly in time with Homo sapiens in the
      region, but we do not know if or how the two species interacted.

PMID- 15510147
TI  - Effect of extrinsic mortality on the evolution of senescence in guppies.
AB  - Classical theories for the evolution of senescence predict that organisms that
      experience low mortality rates attributable to external factors, such as disease
      or predation, will evolve a later onset of senescence. Here we use patterns of
      senescence in guppies derived from natural populations that differ in mortality
      risk to evaluate the generality of these predictions. We have previously found
      that populations experiencing higher mortality rates evolve earlier maturity and
      invest more in reproduction, as predicted by evolutionary theory. We report here
      that these same populations do not have an earlier onset of senescence with
      respect to either mortality or reproduction but do with respect to swimming
      performance, which assesses neuromuscular function. This mosaic pattern of
      senescence challenges the generality of the association between decreased
      extrinsic mortality and delayed senescence and invites consideration of more
      derived theories for the evolution of senescence.

PMID- 15510148
TI  - Population density drives the local evolution of a threshold dimorphism.
AB  - Evolution can favour more than one reproductive tactic among conspecifics of the
      same sex. Under the conditional evolutionarily stable strategy, individuals adopt
      the tactic that generates the highest fitness return for their status: large
      males guard females, whereas small males sneak copulations. Tactics change at the
      status at which fitness benefits switch from favouring one tactic to favouring
      the alternative. This 'switchpoint' is expressed in many species as a threshold
      between divergent morphologies. Environmental and demographic parameters that
      influence the relative fitness of male tactics are predicted to determine a
      population's switchpoint and consequently whether the population is monomorphic
      or dimorphic. Here we show threshold evolution in the forceps dimorphism of the
      European earwig Forficula auricularia and document the transition from completely
      monomorphic to classical male-dimorphic populations over a distance of only 40
      km. Because the superior fighting ability of the dominant morph will be more
      frequently rewarded at high encounter rates, population density is likely to be a
      key determinant of the relative fitness of the alternative tactics, and
      consequently the threshold. We show that, as predicted, population density
      correlates strongly with the shift in threshold, and that this factor drives the
      local evolution of the male dimorphism in these island populations. Our data
      provide evidence for the origin of phenotypic diversity within populations,
      through the evolution of a switchpoint in a conditional strategy that has
      responded to local population density.

PMID- 15510149
TI  - Non-mitochondrial complex I proteins in a hydrogenosomal oxidoreductase complex.
AB  - Trichomonas vaginalis is a unicellular microaerophilic eukaryote that lacks
      mitochondria yet contains an alternative organelle, the hydrogenosome, involved
      in pyruvate metabolism. Pathways between the two organelles differ substantially:
      in hydrogenosomes, pyruvate oxidation is catalysed by pyruvate:ferredoxin
      oxidoreductase (PFOR), with electrons donated to an [Fe]-hydrogenase which
      produces hydrogen. ATP is generated exclusively by substrate-level
      phosphorylation in hydrogenosomes, as opposed to oxidative phosphorylation in
      mitochondria. PFOR and hydrogenase are found in eubacteria and amitochondriate
      eukaryotes, but not in typical mitochondria. Analyses of mitochondrial genomes
      indicate that mitochondria have a single endosymbiotic origin from an alpha
      proteobacterial-type progenitor. The absence of a genome in trichomonad
      hydrogenosomes precludes such comparisons, leaving the endosymbiotic history of
      this organelle unclear. Although phylogenetic reconstructions of a few proteins
      indicate that trichomonad hydrogenosomes share a common origin with mitochondria,
      others do not. Here we describe a novel NADH dehydrogenase module of respiratory
      complex I that is coupled to the central hydrogenosomal fermentative pathway to
      form a hydrogenosomal oxidoreductase complex that seems to function independently
      of quinones. Phylogenetic analyses of hydrogenosomal complex I-like proteins
      Ndh51 and Ndh24 reveal that neither has a common origin with mitochondrial
      homologues. These studies argue against a vertical origin of trichomonad
      hydrogenosomes from the proto-mitochondrial endosymbiont.

PMID- 15510152
TI  - Making the match.

PMID- 15510150
TI  - The genome of Cryptosporidium hominis.
AB  - Cryptosporidium species cause acute gastroenteritis and diarrhoea worldwide. They
      are members of the Apicomplexa--protozoan pathogens that invade host cells by
      using a specialized apical complex and are usually transmitted by an invertebrate
      vector or intermediate host. In contrast to other Apicomplexans, Cryptosporidium
      is transmitted by ingestion of oocysts and completes its life cycle in a single
      host. No therapy is available, and control focuses on eliminating oocysts in
      water supplies. Two species, C. hominis and C. parvum, which differ in host
      range, genotype and pathogenicity, are most relevant to humans. C. hominis is
      restricted to humans, whereas C. parvum also infects other mammals. Here we
      describe the eight-chromosome approximately 9.2-million-base genome of C.
      hominis. The complement of C. hominis protein-coding genes shows a striking
      concordance with the requirements imposed by the environmental niches the
      parasite inhabits. Energy metabolism is largely from glycolysis. Both aerobic and
      anaerobic metabolisms are available, the former requiring an alternative electron
      transport system in a simplified mitochondrion. Biosynthesis capabilities are
      limited, explaining an extensive array of transporters. Evidence of an apicoplast
      is absent, but genes associated with apical complex organelles are present. C.
      hominis and C. parvum exhibit very similar gene complements, and phenotypic
      differences between these parasites must be due to subtle sequence divergence.

PMID- 15510153
TI  - Fast Track: charting the course of your postdoc.

PMID- 15510155
TI  - Recruiters and industry. Get a foot in the door.

PMID- 15510156
TI  - Graduate journal: PhD limitations.

PMID- 15510157
TI  - Epstein-Barr virus: 40 years on.
AB  - Epstein-Barr virus (EBV) was discovered 40 years ago from examining electron
      micrographs of cells cultured from Burkitt's lymphoma, a childhood tumour that is
      common in sub-Saharan Africa, where its unusual geographical distribution - which
      matches that of holoendemic malaria -indicated a viral aetiology. However, far
      from showing a restricted distribution, EBV - a gamma-herpesvirus - was found to
      be widespread in all human populations and to persist in the vast majority of
      individuals as a lifelong, asymptomatic infection of the B-lymphocyte pool.
      Despite such ubiquity, the link between EBV and 'endemic' Burkitt's lymphoma
      proved consistent and became the first of an unexpectedly wide range of
      associations discovered between this virus and tumours.

PMID- 15510158
TI  - Genetic predisposition to colorectal cancer.
AB  - High-penetrance mutations in several genes have been identified that contribute
      to hereditary colorectal cancer. The role of these mutations in cancer
      pathogenesis is well understood and their detection is successfully used in
      clinical diagnosis. In stark contrast, our understanding of the influence of low
      penetrance mutations that account for most of the remaining familial cases of
      colorectal cancer, as well as an unknown proportion of sporadic cases, is far
      less advanced. Extensive ongoing research into low-penetrance, multifactorial
      predisposition to colorectal cancer is now beginning to bear fruit, with
      important implications for understanding disease aetiology and developing new
      diagnostic, preventive and therapeutic strategies.

PMID- 15510159
TI  - Polyamines and cancer: old molecules, new understanding.
AB  - The amino-acid-derived polyamines have long been associated with cell growth and
      cancer, and specific oncogenes and tumour-suppressor genes regulate polyamine
      metabolism. Inhibition of polyamine synthesis has proven to be generally
      ineffective as an anticancer strategy in clinical trials, but it is a potent
      cancer chemoprevention strategy in preclinical studies. Clinical trials, with
      well-defined goals, are now underway to evaluate the chemopreventive efficacy of
      inhibitors of polyamine synthesis in a range of tissues.

PMID- 15510160
TI  - Post-translational modification of p53 in tumorigenesis.
AB  - Interest in the tumour suppressor p53 has generated much information regarding
      the complexity of its function and regulation in carcinogenesis. However, gaps
      still exist in our knowledge regarding the role of p53 post-translational
      modifications in carcinogenesis and cancer prevention. A thorough understanding
      of p53 will be extremely useful in the development of new strategies for treating
      and preventing cancer, including restoration of p53 function and selective
      killing of tumours with mutant TP53.

PMID- 15510161
TI  - High interstitial fluid pressure - an obstacle in cancer therapy.
AB  - Many solid tumours show an increased interstitial fluid pressure (IFP), which
      forms a barrier to transcapillary transport. This barrier is an obstacle in
      tumour treatment, as it results in inefficient uptake of therapeutic agents.
      There are a number of factors that contribute to increased IFP in the tumour,
      such as vessel abnormalities, fibrosis and contraction of the interstitial
      matrix. Lowering the tumour IFP with specific signal-transduction antagonists
      might be a useful approach to improving anticancer drug efficacy.

PMID- 15510162
TI  - Hallmarks of 'BRCAness' in sporadic cancers.
AB  - Germline mutations in the BRCA1, BRCA2 and Fanconi anaemia genes confer cancer
      susceptibility, and the proteins encoded by these genes have distinct functions
      in related DNA-repair processes. Emerging evidence indicates that these processes
      are disrupted by numerous mechanisms in sporadic cancers. Collectively, there are
      properties that define 'BRCAness' - that is, traits that some sporadic cancers
      share with those occurring in either BRCA1- or BRCA2-mutation carriers. These
      common properties might have important implications for the clinical management
      of these cancers.

PMID- 15510163
TI  - A vision for the National Cancer Program in the United States.
AB  - The intersection of two noble endeavors - the scientists' quest to understand
      life itself and the physicians' dedication to relieve suffering and prolong life 
      came into sharp focus in 1971 with the United States National Cancer Act. This
      focus has led to an exponential expansion of our understanding of cancer at the
      genetic, molecular and cellular levels, and concomitant advances in our ability
      to disrupt the disease process through prevention, early detection and successful
      treatment. At the National Cancer Institute we are committed to capitalize on
      these achievements. A new era is now within our grasp, a time when no one suffers
      or dies as a result of cancer.

PMID- 15510164
TI  - Chromosome 21 and down syndrome: from genomics to pathophysiology.
AB  - The sequence of chromosome 21 was a turning point for the understanding of Down
      syndrome. Comparative genomics is beginning to identify the functional components
      of the chromosome and that in turn will set the stage for the functional
      characterization of the sequences. Animal models combined with genome-wide
      analytical methods have proved indispensable for unravelling the mysteries of
      gene dosage imbalance.

PMID- 15510165
TI  - Encoded evidence: DNA in forensic analysis.
AB  - Sherlock Holmes said "it has long been an axiom of mine that the little things
      are infinitely the most important", but never imagined that such a little thing,
      the DNA molecule, could become perhaps the most powerful single tool in the
      multifaceted fight against crime. Twenty years after the development of DNA
      fingerprinting, forensic DNA analysis is key to the conviction or exoneration of
      suspects and the identification of victims of crimes, accidents and disasters,
      driving the development of innovative methods in molecular genetics, statistics
      and the use of massive intelligence databases.

PMID- 15510166
TI  - Computational approaches to unveiling ancient genome duplications.
AB  - Recent analyses of complete genome sequences have revealed that many genomes have
      been duplicated in their evolutionary past. Such events have been associated with
      important biological transitions, major leaps in evolution and adaptive
      radiations of species. Here, we consider recently developed computational methods
      to detect such ancient large-scale gene duplication events. Several new
      approaches have been used to show that large-scale gene duplications are more
      common than previously thought.

PMID- 15510167
TI  - Genetic predisposition to cancer - insights from population genetics.
AB  - Individuals differ in their inherited tendency to develop cancer. Major single
      gene defects that cause early cancer onset have been known for many years from
      their inheritance patterns, and inherited defects that have weaker effects on
      predisposition were also suspected to exist. Recent progress in cancer genetics
      has identified specific loci that are involved in cancer progression, many of
      which have key roles in DNA repair, cell-cycle control and cell-death pathways.
      Those loci, which are often mutated somatically during cancer progression,
      sometimes also contain inherited mutations. Recent genetic studies and
      quantitative population-genetic analyses provide a framework for understanding
      the frequency of inherited mutations and the consequences of these mutations for
      increased predisposition to cancer.

PMID- 15510168
TI  - How did alternative splicing evolve?
AB  - Alternative splicing creates transcriptome diversification, possibly leading to
      speciation. A large fraction of the protein-coding genes of multicellular
      organisms are alternatively spliced, although no regulated splicing has been
      detected in unicellular eukaryotes such as yeasts. A comparative analysis of
      unicellular and multicellular eukaryotic 5' splice sites has revealed important
      differences - the plasticity of the 5' splice sites of multicellular eukaryotes
      means that these sites can be used in both constitutive and alternative splicing,
      and for the regulation of the inclusion/skipping ratio in alternative splicing.
      So, alternative splicing might have originated as a result of relaxation of the
      5' splice site recognition in organisms that originally could support only
      constitutive splicing.

PMID- 15510169
TI  - Timeline: Raising the profile of genetics in primary care.
AB  - Primary care practitioners recognize that genetics is relevant to their daily
      practice, for example, for detecting and managing the risk of multifactorial
      disorders and genetic reproductive risks, and, in future, for targeted drug
      therapy. However, they lack confidence in their ability to apply genetic
      approaches. In fact, genetics is already ingrained in current practice, and the
      development of appropriate guidelines and web-based information resources will
      help practitioners to make personalized genetic risk assessment a part of
      holistic, patient-oriented primary health care.

PMID- 15510170
TI  - Beyond race: towards a whole-genome perspective on human populations and genetic
      variation.
AB  - The renewed emphasis on population-specific genetic variation, exemplified most
      prominently by the International HapMap Project, is complicated by a
      longstanding, uncritical reliance on existing population categories in genetic
      research. Race and other pre-existing population definitions (ethnicity,
      religion, language, nationality, culture and so on) tend to be contentious
      concepts that have polarized discussions about the ethics and science of research
      into population-specific human genetic variation. By contrast, a broader
      consideration of the multiple historical sources of genetic variation provides a
      whole-genome perspective on the ways i n which existing population definitions
      do, and do not, account for how genetic variation is distributed among
      individuals. Although genetics will continue to rely on analytical tools that
      make use of particular population histories, it is important to interpret
      findings in a broader genomic context.

PMID- 15510171
TI  - Genetic equity.
AB  - This paper proposes, elaborates and defends a principle of genetic equity. In
      doing so it articulates, explains and justifies what might be meant by the
      concept of 'human dignity' in a way that is clear, defensible and consistent
      with, but by no means the same as, the plethora of appeals to human dignity found
      in contemporary bioethics, and more particularly in international instruments on
      bioethics. We propose the following principle of genetic equity: humans are born
      equal; they are entitled to freedom from discrimination and equality of
      opportunity to flourish; genetic information may not be used to limit that
      equality.

PMID- 15510172
TI  - Potential oncogene activity of the woodchuck hepatitis post-transcriptional
      regulatory element (WPRE).

PMID- 15510173
TI  - VEGF165 and angiopoietin-1 decreased myocardium infarct size through
      phosphatidylinositol-3 kinase and Bcl-2 pathways.
AB  - Angiogenic growth factors, vascular endothelial growth factor (VEGF) and
      angiopoietin-1 (Ang1) could decrease myocardial infarct size, which was assumed
      to be related with newly formed capillaries. We doubted that these capillaries
      could do this solely and the potential protective mechanisms of VEGF and Ang1 on
      myocardium need to be evaluated. Three types of adenoviruses encoding human
      VEGF(165) (Ad-VEGF(165)), human angiopoietin-1 (Ad-Ang1) and green fluorescent
      protein (Ad-GFP, as a parallel control) were constructed. Experiments were taken
      both in vitro and in vivo. As in vitro, the antiapoptosis effect of VEGF(165),
      Ang1 and VEGF(165)+Ang1 on cardiac myoblasts was observed, which seemed to be
      related with the activation of phosphatidylinositol-3 kinase and Bcl-2 pathways.
      As in vivo, adenoviruses were intramyocardially injected immediately after the
      ligation of the left anterior descending coronay arteries in rats. The results
      showed positive effect of VEGF(165), Ang1 and VEGF(165)+Ang1 on decreasing the
      myocardial infarct size at the 7th day. Myocardial PI-3K activity and Bcl-2
      expression were elevated relatively at the 3rd day. The protective effect of
      VEGF(165) and Ang1 on the myocardium may broaden their functional research and
      contribute to their clinical use in the future.

PMID- 15510174
TI  - Vector integration: location, location, location.

PMID- 15510175
TI  - Radioiodine therapy of colon cancer following tissue-specific sodium iodide
      symporter gene transfer.
AB  - We investigated the feasibility of using radioiodine therapy in colon carcinoma
      cells (HCT 116) following tumor-specific expression of the human sodium iodide
      symporter (hNIS) using the carcinoembryonic antigen (CEA) promoter. HCT 116 cells
      were stably transfected with an expression vector, in which hNIS cDNA has been
      coupled to a CEA promoter fragment. This promoter is responsible for tissue
      specific expression of CEA in gastrointestinal tract epithelium, and has been
      shown to target therapeutic genes to colorectal cancer cells. Functional NIS
      expression was confirmed by iodide uptake assay, Western blot analysis,
      immunostaining and in vitro clonogenic assay. The stably transfected HCT 116
      cells concentrated (125)I about 10-fold in vitro without evidence of iodide
      organification. In contrast, transfection of control cancer cells without CEA
      expression did not result in iodide accumulation. Western blot analysis using a
      hNIS-specific antibody revealed a band of approximately 90 kDa. In addition,
      immunostaining of stably transfected HCT 116 cells revealed hNIS-specific
      membrane-associated immunoreactivity. In an in vitro clonogenic assay
      approximately 95% of stably transfected HCT 116 cells were killed by exposure to
      (131)I, while only about 5% of NIS-negative control cells were killed. Further,
      using an adenovirus carrying the NIS gene linked to the CEA promoter, high levels
      of tumor-specific radioiodide accumulation were induced in HCT 116 cells. In
      conclusion, a therapeutic effect of (131)I has been demonstrated in colon
      carcinoma cells following induction of tumor-specific iodide uptake activity by
      CEA promoter-directed NIS expression in vitro. This study demonstrates the
      potential of NIS as a therapeutic gene allowing radioiodine therapy of colon
      cancer following tumor-specific NIS gene transfer.

PMID- 15510176
TI  - Tumor cell targeted gene delivery by adenovirus 5 vectors carrying knobless
      fibers with antibody-binding domains.
AB  - Most human carcinoma cell lines lack the high-affinity receptors for adenovirus
      serotype 5 (Ad5) at their surface and are nonpermissive to Ad5. We therefore
      tested the efficiency of retargeting Ad5 to alternative cellular receptors via
      immunoglobulin (Ig)-binding domains inserted at the extremity of short-shafted,
      knobless fibers. The two recombinant Ad5's constructed, Ad5/R7-Z(wt)-Z(wt) and
      Ad5/R7-C2-C2, carried tandem Ig-binding domains from Staphylococcal protein A
      (abbreviated Z(wt)) and from Streptococcal protein G (C2), respectively. Both
      viruses bound their specific Ig isotypes with the expected affinity. They
      transduced human carcinoma cells independently of the CAR pathway, via cell
      surface receptors targeted by specific monoclonal antibodies, that is, EGF-R on
      A549, HT29 and SW1116, HER-2/neu on SK-OV-3 and SK-BR-3, CA242 (epitope
      recognized by the monoclonal antibody C242) antigen on HT29 and SW1116, and PSMA
      (prostate-specific membrane antigen) expressed on HEK-293 cells, respectively.
      However, Colo201 and Colo205 cells were neither transduced by targeting CA242 or
      EGF-R nor were LNCaP cells transduced by targeting PSMA. Our results suggested
      that one given surface receptor could mediate transduction of certain cells but
      not others, indicating that factors and steps other than cell surface expression
      and virus-receptor interaction are additional determinants of Ad5-mediated
      transduction of tumor cells. Using penton base RGD mutants, we found that one of
      these limiting steps was virus endocytosis.

PMID- 15510177
TI  - Sonic hedgehog gene-enhanced tissue engineering for bone regeneration.
AB  - Improved methods of bone regeneration are needed in the craniofacial
      rehabilitation of patients with significant bone deficits secondary to tumor
      resection, congenital deformities, and prior to prosthetic dental reconstruction.
      In this study, a gene-enhanced tissue-engineering approach was used to assess
      bone regenerative capacity of Sonic hedgehog (Shh)-transduced gingival
      fibroblasts, mesenchymal stem cells, and fat-derived cells delivered to rabbit
      cranial bone defects in an alginate/collagen matrix. Human Shh cDNA isolated from
      fetal lung tissue was cloned into the replication-incompetent retroviral
      expression vector LNCX, in which the murine leukemia virus retroviral LTR drives
      expression of the neomycin-resistance gene. The rat beta-actin enhancer/promoter
      complex was engineered to drive expression of Shh. Reverse transcriptase
      polymerase chain reaction analysis demonstrated that the transduced primary
      rabbit cell populations expressed Shh RNA. Shh protein secretion was confirmed by
      enzyme-linked immunosorbent assay (ELISA). Alginate/ type I collagen constructs
      containing 2 x 10(6) Shh-transduced cells were introduced into male New Zealand
      White rabbit calvarial defects (8 mm). A total of eight groups (N=6) were
      examined: unrestored empty defects, matrix alone, matrix plus the three cell
      populations transduced with both control and Shh expression vectors. The bone
      regenerative capacity of Shh gene enhanced cells was assessed grossly,
      radiographically and histologically at 6 and 12 weeks postimplantation. After 6
      weeks, new full thickness bone was seen emanating directly from the
      alginate/collagen matrix in the Shh-transduced groups. Quantitative two
      dimensional digital analysis of histological sections confirmed statistically
      significant (P<0.05) amounts of bone regeneration in all three Shh-enhanced
      groups compared to controls. Necropsy failed to demonstrate any evidence of
      treatment-related side effects. This is the first study to demonstrate that Shh
      delivery to bone defects, in this case through a novel gene-enhanced tissue
      engineering approach, results in significant bone regeneration. This encourages
      further development of the Shh gene-enhanced tissue-engineering approach for bone
      regeneration.

PMID- 15510178
TI  - Internet websites selling herbal treatments for erectile dysfunction.
AB  - The objective of the study was to investigate the safety and reliability of
      internet websites selling and providing medical information regarding herbal
      substitutes for Viagra. Using keywords 'Herbal' and 'Viagra', websites selling
      and providing medical information regarding herbal substitutes were identified.
      The top 50 sequential sites were assessed for safety and reliability against the
      Health on the Net (HON) criteria. Medically trained staff provided information in
      only 21% of the sites yet just 24% stated that the information was not a
      replacement for medical advice. No sites warned patients about erectile
      dysfunction (ED)-associated cardiovascular disease. In all, 88 and 70% of sites
      indicated drug efficacy and ingredients but only 36 and 21% provided
      contraindications and side effects, respectively. All sites fell short of the HON
      requirements. In conclusion, acquiring medical information and herbal substitutes
      for ED from the internet is convenient and easy. However, patients should be
      cautious as safety and reliability of this approach is poor.

PMID- 15510179
TI  - Relationship between smoking and erectile dysfunction.
AB  - We estimated the effects of smoking on the risk and prognosis of erectile
      dysfunction (ED), and of ED on smoking behavior. The follow-up sample consisted
      of the 1442 men aged 50-75 y, who responded to both baseline and follow-up
      questionnaires. We estimated the effect of smoking on the incidence of ED among
      the 1130 men free from ED, ED on risk to start smoking in the 502 nonsmokers,
      smoking on the prognosis of ED among the 312 with ED and ED on quitting smoking
      among the 292 current smokers at baseline. Risk of ED increased nonsignificantly
      with smoking (odds ratio (OR)=1.4), while ED recovery reduced (OR=0.6).
      Therefore, there was the ratio of 2.3 (1.4/0.6) describing the total effect of
      smoking on the risk of ED. Both quitting (OR=1.7) and starting (OR=1.9) smoking
      were rare and nonsignificantly higher in men with ED. Most of the OR estimates on
      smoking-ED relationships were not statistically significant, probably due to
      small numbers. There are two bidirectional relations between ED and smoking.
      Those who smoked had a higher risk of ED than nonsmokers. The men with ED were
      more likely to start smoking than those free from ED. The estimates of effects
      were not statistically significant, but they were consistent with each other and
      with the hypothesis that smoking causes ED and ED causes smoking. The recovery
      from ED was less in smokers than among nonsmokers, and current smokers with ED
      were more likely to stop smoking than men free from ED. Numbers were few and
      estimates of effects were not significant, but consistent with the hypothesis of
      smoking preventing recovery from ED and ED improving the success of smoking
      cessation. Such transitions in four directions explain indirectly the known
      positive association between the prevalence of smoking and the prevalence of ED.

PMID- 15510180
TI  - A case of erectile dysfunction associated with chronic methyl bromide
      intoxication.

PMID- 15510181
TI  - Response of the internal reproductive organs to clitoral stimulation: the
      clitorouterine reflex.
AB  - We investigated hypothesis that uterine erection, elevation and enlargement
      during sexual response are reflex and result from penis buffeting the glans
      clitoris (GC). In 23 healthy women, two recording electrodes were applied to the
      uterine mucosa and one to cervix uteri (CU). GC was stimulated electrically and
      mechanically by pencil electrode. The uterine and CU pressures were measured.
      Tests were repeated after anesthetization of the uterus or GC. Uterine electrodes
      recorded slow waves, followed by random bursts of action potentials (APs). No
      waves registered from CU. Electrical or mechanical GC stimulation eliminated
      uterine electric waves, but anesthetized GC did not, nor did GC stimulation while
      the uterus anesthetized. Uterine pressure declined on electrical or mechanical
      stimulation. Results suggest presence of reproducible reflex relationship between
      GC and the uterus, we call 'clitorouterine reflex'. GC buffeting seems to evoke
      reflex and initiate uterine responses. Reflex may prove of diagnostic
      significance in sexual disorders.

PMID- 15510182
TI  - Role of genital sensory information in the control of the functioning of the
      spinal generator for ejaculation.
AB  - An intrinsic spinal rhythm mediates fictive ejaculation (FE). In this study, the
      effect of genital sensory stimulation on the functioning of the spinal generator
      of ejaculation was investigated. To this aim, the effect of (a) stimulation of
      internal and external genital structures; (b) repeated elicitation of FE and (c)
      genital stimulation during in progress expression of FE on the rhythmic genital
      motor pattern of ejaculation (GMPE) was analysed in sexually experienced, spinal
      male rats. Results showed that the spinal intrinsic ejaculatory rhythm can be
      modulated by genital inputs, and that repeated stimulation modifies this rhythm,
      progressively inhibiting its expression. Finally, in progress GMPEs could be
      reset by overlapping genital stimulation, supporting the notion of the spinal
      cord mediating the inhibition of FE following repeated genital inflow. Results
      reveal the nature of the modulatory role that genital afferent information exerts
      on the expression of FE.

PMID- 15510183
TI  - Heavy smoking is an important risk factor for erectile dysfunction in young men.
AB  - Clinical and basic science studies provide strong indirect evidence that smoking
      may affect penile erection. The objective of this retrospective research was to
      investigate the role of smoking for erectile dysfunction (ED) in order to obtain
      some insight into the prevention of ED. We reviewed the data from 860 male
      patients aged between 18 and 44 visited during the period January 1999 to
      December 2002. The patients were divided into three groups: smokers, never
      smokers and former smokers. All patients were submitted of medical history, such
      as, IIEF 5 Questionnaire, physical examination, serum levels of glucose,
      cholesterol, prolactin and free testosterone. Our data were compared with ISTAT
      (Italian Institute of Statistics) and data on the Italian population of smokers.
      We have stratified the data by age and area of residence. The 860 patients, mean
      age 32.4 y old (range 18-44), are distributed into three groups: smokers 460
      (53.5%), never smokers 320 (37.2%) and former smokers 80 (9.3%). Current smokers
      in our series are 460 (53.5%) in comparison to 34.7% of male current smokers in
      Italy, in the same range (18-44). Out of 860, 337 are patients who smoked more
      than 20 cigarettes per/day (39.2%) and these data are extremely interesting;
      while comparing the same aged men through ISTAT, it is found that only 4% are
      heavy smokers. On analysing the incidence of heavy smoking in middle-aged
      patients affected by ED with the whole Italian population by means of ISTAT,
      taking into account males with the same age range and area of residence, it was
      shown that the data of our population (sample) compared all Italian middle-aged
      patients are 39.2 vs 4%; this explains the need for education within a
      comprehensive smoking cessation programme, and should be reserved especially for
      young smokers, in order to be aware and informed of the effect of tobacco on
      erectile function.

PMID- 15510184
TI  - Clinical efficacy of Apomorphine SL in erectile dysfunction of diabetic men.
AB  - Although subgroup analyses from large randomised premarketing studies have shown
      that Apomorphine SL enhances the percentage of erections firm enough for sexual
      intercourse in diabetic men, the clinical role of the drug in this patient
      population remains to be elucidated. The aim of the present study was to assess
      the efficacy of Apomorphine SL in diabetic males with erectile dysfunction (ED)
      and to identify factors predicting those who may benefit from the treatment. A
      total of 130 diabetic patients were randomised to receive either four tablets of
      3 mg Apomorphine or a matching placebo. Assessments of efficacy comprised the
      erectile function (EF) domain of the International Index of Erectile Function
      (IIEF) and the one-item global efficacy question (GEQ). Patients with both a
      positive response to the GEQ and an improvement of at least 5 points in the EF
      domain of the IIEF were considered responders and subanalysed by several
      parameters indicative of the severity of both ED and diabetes. Response rate was
      17% after placebo and 22% after Apomorphine SL. The EF domain of the IIEF and
      both questions 3 and 4 scores did not significantly improve in either of the two
      arms over the baseline. A younger age and a lower Hb1Ac were significantly linked
      to the status of responder in the Apomorphine arm. Apomorphine SL failed to show
      a statistically significant benefit over a placebo, but 22% of patients had a
      clinically significant erectile response. These figures seem to suggest that the
      drug has a limited use for ED diabetic patients.

PMID- 15510185
TI  - Penile measurements in normal adult Jordanians and in patients with erectile
      dysfunction.
AB  - The purpose of this work was to determine penile size in adult normal (group one,
      271) and impotent (group two, 109) Jordanian patients. Heights of the patients,
      the flaccid and fully stretched penile lengths were measured in centimeters in
      both groups. Midshaft circumference in the flaccid state was recorded in group
      one. Penile length in the fully erect penis was measured in group two. In group
      one mean midshaft circumference was 8.98+/-1.4, mean flaccid length was mean
      9.3+/-1.9, and mean stretched length was 13.5+/-2.3. In group two, mean flaccid
      length was 7.7+/-1.3, and mean stretched length was 11.6+/-1.4. The mean of fully
      erect penile length after trimex injection was 11.8+/-1.5. In group 1 there was
      no correlation between height and flaccid length or stretched length, but there
      was a significant correlation between height and midpoint circumference, flaccid
      and stretched lengths, and between stretched lengths and midpoint circumference.
      In group 2 there was no correlation between height and flaccid, stretched, or
      fully erect lengths. On the other hand, there was a significant correlation
      between the flaccid, stretched and fully erect lengths. Comparing group 1 and
      group 2, the patients in group 1 were slightly older than in group 2 (P=0.035),
      but there was no significant difference in their height. However, there was a
      significant difference regarding the mean flaccid length 9.3 vs 7.7 (P=0.001),
      and the mean stretched length 13.5 vs 11.6 (P=0.000). We divided both groups into
      those who are less than 40 y of age, and over 40 y old. There was no statistical
      difference in the stretched and flaccid lengths between the younger and older
      individuals in each group. However, when we compared the stretched and flaccid
      lengths in those of less than 40 y old in group 1 and 2, a significant difference
      was noticed. Similarly, a significant difference in the stretched and flaccid
      lengths in those patients over 40 y of age was also present.

PMID- 15510186
TI  - Sexual function after permanent 125I-brachytherapy for prostate cancer.
AB  - We prospectively assessed patients' erectile function (EF) using the
      International Index of Erectile Function (IIEF) and a global assessment
      questionnaire (GAQ) following permanent 125I-brachytherapy for localized prostate
      cancer. Of 378 treated patients, 220 had a minimal 2-y follow-up and 131/220 were
      sexually active prior to brachytherapy, with an EF domain score of > or = 11
      (study group). Patients were allowed sildenafil at any time of the study. The
      patients' mean EF score, without excluding patients who used sildenafil, dropped
      within 3 months after brachytherapy, recovered at the end of the first year and
      remained unchanged for at least up to 2 y after treatment regardless of the
      addition of neoadjuvant hormone therapy to 125I-brachytherapy. Analysis of the
      GAQ revealed that 80% of the patients were satisfied with their sexual function
      up to 3 y after treatment. Any detrimental effect of permanent brachytherapy with
      or without the addition of hormone therapy on EF is reversible, and recovery is
      expected at 1 y after treatment in most patients.

PMID- 15510187
TI  - The effect of overactive bladder syndrome on the sexual quality of life in Korean
      young and middle aged women.
AB  - Some reports showed that urinary incontinence (UI) or female lower urinary tract
      symptoms (LUTS) affect life quality and sexual activity. In clinical practice, it
      is commonly found that not only the symptoms of UI but also overactive bladder
      (OAB) syndrome affect daily lifestyle and sexual activity, especially in women in
      the most active era in their social and personal life. However, there is lack of
      data proving the effect of OAB syndrome on sexual activity or sexual life quality
      in sexually active age group. This study aimed at evaluating the effect of OAB
      syndrome and UI on the sexual activity and on the sexual quality of life (QoL) of
      Korean women age from 20s to 40s. We investigated 3372 women aged between 20 and
      49 y, enrolled via a multicenter internet survey. A structured questionnaire was
      used to collect data about their LUTS and sexual activities. The prevalence of
      OAB syndrome and UI in 3372 women was 12.7 and 21.0%, respectively. Mean subject
      age was 26.4+/-4.8 y and 79.5% of subjects were 20-29 y old. Having OAB syndrome
      or UI were found to be significant predictors of sexual life problems (OAB
      syndrome: OR=5.08, 95% CI=3.68-7.01; UI: OR=4.16, 95% CI=3.06-5.67). Sexual
      activity was significantly reduced in OAB syndrome and UI versus the asymptomatic
      group (OAB syndrome: OR=4.8, 95% CI=3.14-6.83; UI: OR=3.9, 95% CI=2.81-5.27).
      This study is the first internet-based study concerning the sexual QoL in UI and
      OAB syndrome. In this study, OAB syndrome was found to cause a greater
      deterioration in the sexual QoL than UI. These results suggest that these
      symptoms have a significant impact upon women's personal and social lives and
      markedly affect the QoL.

PMID- 15510188
TI  - Phentolamine relaxes human corpus cavernosum by a nonadrenergic mechanism
      activating ATP-sensitive K+ channel.
AB  - To investigate the pharmacodynamics of phentolamine in human corpus cavernosum
      (HCC) with special attention to the role of the K+ channels. Strips of HCC
      precontracted with nonadrenergic stimuli and kept in isometric organ bath
      immersed in a modified Krebs-Henseleit solution enriched with guanethidine and
      indomethacine were used in order to study the mechanism of the phentolamine
      induced relaxation. Phentolamine caused relaxation (approximately 50%) in HCC
      strips precontracted with K+ 40 mM. This effect was not blocked by tetrodotoxin
      (1 microM) (54.6+/-4.6 vs 48.9+/-6.4%) or (atropine (10 microM) (52.7+/-6.5 vs
      58.6+/-5.6%). However, this relaxation was significantly attenuated by L-NAME
      (100 microM) (59.7+/-5.8 vs 27.8+/-7.1%; P<0.05; n = 8) and ODQ (100 microM)
      (62.7+/-5.1 vs 26.8+/-3.9%; P<0.05; n = 8). Charybdotoxin and apamin (K(Ca)
      channel blockers) did not affect the phentolamine relaxations (54.6+/-4.6 vs
      59.3+/-5.2%). Glibenclamide (100 microM), an inhibitor of K(ATP)-channel, caused
      a significant inhibition (56.7+/-6.3 vs 11.3+/-2.3%; P<0.05; n = 8) of the
      phentolamine-induced relaxation. In addition, the association of glibenclamide
      and L-NAME almost abolished the phentolamine-mediated relaxation (54.6+/-5.6 vs
      5.7+/-1.4%; P<0.05; n = 8). The results suggest that phentolamine relaxes HCC by
      a nonadrenergic-noncholinergic mechanism dependent on nitric oxide synthase
      activity and activation of K(ATP)-channel.

PMID- 15510189
TI  - Predictors of erectile function improvement in obstructive sleep apnea patients
      with long-term CPAP treatment.
AB  - The long-term effect of treatment with continuous positive airway pressure (CPAP)
      on erectile function was assessed in 60 patients with obstructive sleep apnea
      syndrome (OSAS). Severity of OSAS was evaluated by respiratory disturbance index
      (RDI) and minimal oxygen saturation (OxiMin). Severity of erectile dysfunction
      (ED) was assessed with the five question International Index of Erectile Function
      (IIEF-5) before and after CPAP treatment. Subjects were categorized into three
      groups on the basis of the change in IIEF-5 score: Group 1, no change (n=37);
      Group 2, improvement from 10+/-5.65 to 19.1+/-5.7, P<0.01 (n=12); Group 3,
      worsening from 19.9+/-4.7 to 9.5+/-7.8, P<0.01 (n=11). Group 2 had significantly
      higher RDI and lower OxiMin than the other groups, and was also more compliant
      and satisfied with CPAP. Change in IIEF-5 with CPAP treatment was negatively
      correlated (Pearson coefficient) with OxiMin (r=-0.374), and positively
      correlated with adherence to CPAP treatment (r=0.689). In conclusion, in selected
      patients, CPAP treatment for OSAS may by itself have a positive effect on
      erectile function by improving respiration during sleep. Predictors of erectile
      improvement include high RDI, low OxiMin, and CPAP compliance.

PMID- 15510191
TI  - Evaluation of sexual activity in patients treated with tadalafil: a randomized
      prospective placebo-controlled trial.
AB  - The chronological distribution of sexual intercourses in a group of patients
      treated with tadalafil versus placebo for 3 months was evaluated. In total, 120
      patients with ED were randomized in two groups and treated, respectively, with
      one pill of tadalafil 20 mg or placebo on Tuesday and on Friday. After 3 months,
      we collected data using IIEF and SEP diaries. After 3 months, IIEF score and
      percentages of success SEP diaries increased in the tadalafil group (<0.01)
      versus placebo group. Considering all the successful intercourses of the 3 months
      of tadalafil assumption, the highest percentages were reported within 6-12 h
      range (35%) and 12-24 h range (28%). In tadalafil group, 41% of patients reported
      their first successful intercourse between 1 and 6 h and 78% of patients reported
      the recovery of spontaneous erections. In conclusion, after carrying out the
      first sexual attempt between 1 and 6 h, patients engaged in sexual activity
      between 6 and 24 h.

PMID- 15510190
TI  - Sexual dysfunctions in HCV patients and its correlations with psychological and
      biological variables.
AB  - The frequency of sexual dysfunction (SD) is not very well known in patients with
      chronic hepatitis C. In this study, the prevalence of SD and its correlations
      with psychological and biological variables was assessed in 46 HCV positive
      patients. The mean age of patients was 46.4+/-9.4 y; the mean duration of HCV
      infection was 43.4+/-34.0 months; 52% were male; 89% were living with a spouse.
      SD was assessed using the Arizona Sexual Experiences Scale (ASEX), the level of
      anxiety and depression measured with the Hospital Anxiety and Depression Scale
      (HADS). Biochemical parameters were also assessed. Overall, as indicated by ASEX
      criteria, SD was observed in 35% of our patients. Of 24 males, 21% described SD;
      problems with drive (25%), arousal (17%) and erection (17%) were the most
      frequent complaints. Of 22 female patients, 50% described SD; problems with drive
      (55%) arousal (50%), and reaching orgasm (59%) were the most frequent complaints.
      Total ASEX scores were correlated with age (P<0.07, significant at trend level),
      education (P<0.001), and was higher in female patients (P<0.02). After
      controlling for the effects of age, sex, education, duration of HCV and marital
      status, depression levels could still significantly predict the SD (P<0.05).
      Moreover, even after controlling the effects of all other variables, gamma
      glutamyl transpeptidase (GGT) levels could predict the SD status of the patients
      (P<0.05). Our results indicate that the prevalence of SD was 35% in HCV-infected
      patients and the level of depression and GGT levels were predictive of patients
      SD status.

PMID- 15510192
TI  - Incidence rates of erectile dysfunction in the Dutch general population. Effects
      of definition, clinical relevance and duration of follow-up in the Krimpen Study.
AB  - This study aims to describe the incidence rate of erectile dysfunction (ED) in
      older men in the Netherlands according to three definitions. The influence of the
      duration of follow-up on the incidence rate is also explored. In a large
      community-based follow-up study, 1661 men aged 50-75 y completed the
      International Continence Society sex questionnaire and a question on sexual
      activity, at baseline and at a mean of 2.1 and 4.2 y of follow-up. We defined
      'ED' as a report of erections with 'reduced rigidity' or worse; 'Significant_ED'
      as 'severely reduced rigidity' or 'no erections'; and 'Clinically_Relevant_ED' as
      either 'ED' reported as 'quite a problem' or 'a serious problem', or
      'Significant_ED' reported as at least 'a bit of a problem'. Incidence rates of ED
      status were calculated in those men who completed at least one period of follow
      up and were not diagnosed with prostate cancer (n = 1604). For 'ED' the incidence
      rate (cases per 1000 person-years) is 99 and ranges over the 10-y age groups from
      77 (50-59 y) to 205 (70-78 y); for 'Significant_ED' these rates were 33, 21, and
      97, respectively and for 'Clinically_Relevant_ED' 28, 25, and 39, respectively.
      In general, incidence rates should not vary with the duration of follow-up.
      However, for 'ED' the 4.2 y incidence rate is about 69% of the 2.1 y incidence
      rate. This study presents incidence rates, for the general population, as well as
      based on a definition of ED that takes concern/bother into account.
      'Clinically_Relevant_ED' has a lower increase in incidence with increasing age
      than other definitions that do not take concern/bother into account. The
      phenomenon of lower incidence rates with longer duration of follow-up may account
      for the differences in reported incidence rates between different studies. The
      effects of differences related to the duration of follow-up should be taken into
      consideration in future incidence reports.

PMID- 15510193
TI  - Post-marketing surveillance study of the safety and efficacy of sildenafil
      prescribed in primary care to erectile dysfunction patients.
AB  - In order to investigate the safety and efficacy of sildenafil prescribed in
      primary care, a post-marketing surveillance study was undertaken. A total of 651
      men with erectile dysfunction (ED) were enrolled from 31 family physicians in
      Korea from December 1999 to July 2002. Patients were regularly followed up to
      ascertain the safety and efficacy of sildenafil. Of the 651 patients enrolled,
      572 (87.9%) returned for safety evaluation and efficacy assessment. In all, 458
      (80.1%) of 572 patients reported improved erectile function with sildenafil.
      Hypertension, diabetes and low-dose sildenafil were associated with poor
      efficacy. A total of 71 adverse events were reported among 56 patients (8.6%),
      with the most frequent being hot flushes (5.6%), followed by headache (2.6%),
      palpitation (1.0%), anxiety (0.5%) and elevated ALT (0.5%). Only six patients
      (1.0%) discontinued sildenafil as a direct result of adverse events. These
      results suggest that sildenafil prescribed by primary care physicians was well
      tolerated and improved erectile function in patients with ED.

PMID- 15510194
TI  - Comparison of oxidative/antioxidative status of penile corpus cavernosum blood
      and peripheral venous blood.
AB  - The aim of the study is to determine and to compare the oxidative and
      antioxidative status of penile corpus cavernosum and peripheral venous blood. A
      total of 28 adult healthy males were included in the study. Whole blood was
      simultaneously withdrawn from penile corpus cavernosum and the cubital vein and
      their plasma separated. Total antioxidant capacity (TAC), vitamin C, total
      protein, albumin, uric acid, bilirubin and total peroxide (TP) levels of both
      plasma samples were measured and compared. While TAC, total protein, albumin,
      bilirubin and uric acid levels were higher, vitamin C levels were lower in
      cavernosal blood than that of peripheral blood. On the other hand, TP level was
      found to be higher in penile blood samples than that of peripheral blood. We
      thought that the normal erectile process of the penile cavernosal body leads to
      increased production of oxidants as in the mechanism of ischaemia-reperfusion;
      however, the increase of TAC can prevent development of oxidative injury.

PMID- 15510195
TI  - Blood urea nitrogen concentration as a marker of amino-acid intolerance in
      neonates with birthweight less than 1250 g.
AB  - OBJECTIVE: Currently blood urea nitrogen (BUN) is commonly used as a marker of
      protein intolerance in very preterm infants. The purpose of this study was to
      evaluate the relationship between amino-acid intakes and BUN concentrations
      during the early neonatal period in preterm neonates. STUDY DESIGN: Retrospective
      review of BUN concentration data from 121 infants with birthweight <or=1250 g
      receiving exclusive parenteral nutrition over the first 72 hours of life.
      RESULTS: There were 136 separate BUN concentration values. Amino-acid intake
      range was 0 to 3.7 g kg-1 day-1 and nonprotein calorie intake range was 15 to 45
      kcal kg-1 d-1. There was no correlation between BUN concentration and amino-acid
      intake (p=0.2 and r2=0.01). CONCLUSIONS: In parenterally nourished preterm
      neonates amino-acid intake is not correlated with BUN concentration in the first
      days of life. Therefore, limiting amino-acid intake based on BUN concentration is
      not warranted in this patient population.

PMID- 15510196
TI  - Equilibrative nucleoside transporter-2 (hENT2) protein expression correlates with
      ex vivo sensitivity to fludarabine in chronic lymphocytic leukemia (CLL) cells.
AB  - Fludarabine is considered the treatment of choice for most patients with chronic
      lymphocytic leukemia (CLL). We have analyzed the role of plasma membrane
      transporters in nucleoside-derived drug bioavailability and action in CLL cells.
      Among the known plasma membrane transporters, we have previously observed a
      significant correlation between fludarabine uptake via ENT carriers and ex vivo
      sensitivity of CLL cells to fludarabine, although mRNA amounts of the
      equilibrative nucleoside transporters hENT1 and hENT2 do not show any predictive
      response to treatment. In this study, using polyclonal monospecific antibodies we
      have observed a significant correlation between the expression of hENT2 by
      Western blot and fludarabine uptake via hENT carriers and also with ex vivo
      sensitivity of CLL cells to fludarabine. These results suggest that the
      equilibrative nucleoside transporter hENT2 plays a role in fludarabine
      responsiveness in CLL patients.

PMID- 15510197
TI  - Bedside RNA stabilizing kit systems for gene expression analysis of acute
      leukemias: influence of non-neoplastic white blood cells.

PMID- 15510198
TI  - Novel mutations in the FLT3 gene in adult patients with refractory acute myeloid
      leukemia.

PMID- 15510200
TI  - Alemtuzumab in the treatment of relapsed acute lymphoid leukaemia.

PMID- 15510201
TI  - Allogeneic stem cell transplantation reverses the poor prognosis of CML patients
      with deletions in derivative chromosome 9.

PMID- 15510202
TI  - Analysis of efficacy and toxicity of thalidomide in 122 patients with multiple
      myeloma: response of soft-tissue plasmacytomas.

PMID- 15510203
TI  - Efficacy and safety of rasburicase, a recombinant urate oxidase (Elitek), in the
      management of malignancy-associated hyperuricemia in pediatric and adult
      patients: final results of a multicenter compassionate use trial.
AB  - The recombinant urate oxidase, rasburicase (Elitek, Sanofi-Synthelabo, Inc.), has
      recently received regulatory approval for the prevention and treatment of
      hyperuricemia in children with leukemia, lymphoma, and solid tumors. Prior to
      approval, 682 children and 387 adults in the US and Canada received rasburicase
      on compassionate-use basis. Uric acid concentration declined rapidly in both
      adult and pediatric patients after rasburicase treatment. Similar responses were
      observed in patients treated with subsequent courses. Possible drug-related
      adverse events, including allergic reactions, were uncommon. These data confirm
      that rasburicase is effective and safe for the treatment and prophylaxis of
      children and adults with malignancy-associated hyperuricemia.

PMID- 15510204
TI  - Single-agent thalidomide for treatment of first relapse following high-dose
      chemotherapy in patients with multiple myeloma.

PMID- 15510205
TI  - Rapid reconstitution of dendritic cells after allogeneic transplantation of
      CD133+ selected hematopoietic stem cells.

PMID- 15510206
TI  - Development of a D-FISH method to detect DEK/CAN fusion resulting from
      t(6;9)(p23;q34) in patients with acute myelogenous leukemia.
AB  - The t(6;9)(p23;q34)-DEK/CAN fusion occurs with an incidence of 1-5% in adult
      patients with acute myelogenous leukemia (AML) and tends to have an unfavorable
      prognosis at diagnosis. Due to the subtle appearance of this chromosome
      rearrangement, both initial detection and minimal residual disease (MRD) tracking
      by conventional karyotyping can be difficult. Unfortunately, no commercial or
      previously published fluorescence in situ hybridization (FISH) strategies exist
      for this recurrent anomaly. We have developed a highly sensitive assay using dual
      color, double-fusion FISH (D-FISH), which can be used both for initial detection
      and MRD monitoring. We analyzed archived bone marrow samples from 15 patients
      with a previously identified t(6;9)(p23;q34) and 10 corresponding post-treatment
      samples. The results demonstrate that our D-FISH method effectively identified
      all abnormal samples, including a low-level MRD sample that was considered to be
      normal by conventional cytogenetic analysis. Normal value ranges were established
      from 30 negative controls to be < 0.6% when 500 interphase nuclei were analyzed.
      The development of this sensitive D-FISH strategy for the detection of the
      t(6;9)(p23;q34) adds to the AML FISH testing repertoire, and is effective in the
      detection of low-level disease in post-treatment samples in these patients.

PMID- 15510207
TI  - Anagrelide is effective in treating patients with hydroxyurea-resistant
      thrombocytosis in patients with chronic myeloid leukemia.
AB  - We report phase II trial results of the use of oral anagrelide hydrochloride for
      treating 38 patients with hydroxyurea (HU)-resistant thrombocytosis accompanying
      chronic myeloid leukemia (CML). Anagrelide's efficacy was well established during
      a phase II study of more than 400 patients with one of the four
      myeloproliferative disorders: essential thrombocythemia, polycythemia, idiopathic
      myelofibrosis, and CML. In the last subgroup, there were 114 CML patients with
      significant thrombocytosis treated with anagrelide. Out of these patients, 38 had
      symptoms of thrombosis or hemorrhage and had thrombocytosis resistant to HU. They
      were then treated with anagrelide at an initial dose of 2.0 mg/day, followed by
      modifications based upon response and toxicity. In all, 71% of these patients
      responded with platelet reductions of more than 50% in a median time of
      approximately 4 weeks. The response rate was not influenced by age, gender, or
      prior thrombosis or hemorrhage. Importantly, the response rate to anagrelide in
      patients refractory to prior HU was essentially the same as that of the other 76
      CML patients. Treatment with anagrelide was well tolerated and without undue
      toxicity. Reduction of excessive platelet counts by anagrelide sometimes
      occurring in CML may lead to the prevention of thrombohemorrhagic complications
      occurring in this clinical setting and is relevant even in those patients in whom
      imatinib mesylate is primary therapy.

PMID- 15510209
TI  - CD34+ marrow progenitors from MDS patients with high levels of intramedullary
      apoptosis have reduced expression of alpha4beta1 and alpha5beta1 integrins.
AB  - Excessive intramedullary apoptosis is central in the pathogenesis of
      myelodysplastic syndromes (MDS). Growth-inhibiting cytokines, the Fas/FasLigand
      pathway, and autoreactive cytotoxic T-lymphocytes have been identified to be
      important proapoptotic factors in MDS. In normal hematopoiesis, alpha4beta1 and
      alpha5beta1 integrin-mediated interactions between progenitors and fibronectin
      are critical for progenitor cell survival. In this study, we have used flow
      cytometry to quantify the expression levels of members of the beta1 integrin
      family on CD34(+) marrow progenitors in 27 untreated patients with MDS, three
      with s-AML, and 25 control subjects. In MDS, we observed that nonapoptotic
      progenitors significantly downregulate cell surface expression levels of alpha4
      and beta1 integrin chains compared with healthy controls. Downregulation of
      alpha4, beta1, and also alpha5 was present in MDS patients with > or =25%
      apoptotic progenitors, irrespective of their French, American, British
      subcategory. Reduced cell surface expression levels of alpha4, alpha5, and beta1
      did also correlate with decreased in vitro adhesiveness to fibronectin fragments.
      Therefore, our observations suggest that downregulation of alpha4beta1 and
      alpha5beta1 integrins on CD34(+) progenitors could be a newly identified
      proapoptotic mechanism in MDS.

PMID- 15510208
TI  - Induction of gene expression by 5-Aza-2'-deoxycytidine in acute myeloid leukemia
      (AML) and myelodysplastic syndrome (MDS) but not epithelial cells by DNA
      methylation-dependent and -independent mechanisms.
AB  - The methylation inhibitor 5-Aza-2'-deoxycytidine (5-Aza-CdR, decitabine) has
      therapeutic efficacy in acute myeloid leukemia (AML) and myelodysplastic syndrome
      (MDS). Using microarray analysis, we investigated global changes in gene
      expression after 5-Aza-CdR treatment in AML. In the AML cell line OCI-AML2, Aza
      CdR induced the expression of 81 out of 22 000 genes; 96 genes were downregulated
      (> or =2-fold change in expression). RT-PCR analysis of 10 randomly selected
      genes confirmed the changes of expression in AML cells. Similar results were
      obtained with primary AML and MDS cells after treatment with 5-Aza-CdR ex vivo
      and in vivo, respectively. In contrast, significantly fewer changes in gene
      expression and cytotoxicity were detected in normal peripheral blood mononuclear
      and bone marrow cells or transformed epithelial cells treated with 5-Aza-CdR.
      Interestingly, only 50.6% of the induced genes contain putative CpG islands in
      the 5' region. To further investigate the significance of promoter methylation in
      the induced genes, we analyzed the actual methylation status of randomly selected
      5-Aza-CdR-inducible genes. We detected hypermethylation exclusively in the 5'
      region of the myeloperoxidase (MPO) gene. DNA methylation inversely correlated
      with MPO expression in newly diagnosed untreated AML patients (P< or =0.004). In
      contrast, all other analyzed 5-Aza-CdR-inducible genes revealed no CpG
      methylation in the promoter region, suggesting a methylation-independent effect
      of 5-Aza-CdR.

PMID- 15510210
TI  - Translocation t(1;6)(p35.3;p25.2): a new recurrent aberration in "unmutated" B
      CLL.
AB  - Although reciprocal chromosomal translocations are not typical for B-cell chronic
      lymphocytic leukemia (B-CLL), we identified the novel t(1;6)(p35.3;p25.2) in
      eight patients with this disorder. Interestingly, all cases showed lack of
      somatically mutated IgV(H). Clinical, morphological, immunologic, and genetic
      features of these patients are described. Briefly, the age ranged from 33 to 81
      years (median: 62.5 years) and the sex ratio was 6M:2F. Most of the patients
      (6/8) presented with advanced clinical stage. Therapy was required in seven
      cases. After a median follow-up of 28 months, five patients are alive and three
      died from disease evolution. Three cases developed transformation into diffuse
      large B-cell lymphoma. Translocation t(1;6) was found as the primary karyotypic
      abnormality in three patients. Additional chromosomal aberrations included
      changes frequently found in unmutated B-CLL, that is, del(11)(q), trisomy 12 and
      17p aberrations. Fluorescence in situ hybridization analysis performed in seven
      cases allowed us to map the t(1;6) breakpoints to the 1p35.3 and 6p25.2
      chromosomal bands, respectively. The latter breakpoint was located in the genomic
      region coding for MUM1/IRF4, one of the key regulators of lymphocyte development
      and proliferation, suggesting involvement of this gene in the t(1;6). Molecular
      characterization of the t(1;6)(p35.3;p25.2), exclusively found in unmutated
      subtype of B-CLL, is in progress.

PMID- 15510211
TI  - Evidence for D276G and L364I Bcr-Abl mutations in Ph+ leukaemic cells obtained
      from patients resistant to Imatinib.

PMID- 15510212
TI  - Functional characterization of wild-type and mutant human sialin.
AB  - The modification of cell surface lipids or proteins with sialic acid is essential
      for many biological processes and several diseases are caused by defective sialic
      acid metabolism. Sialic acids cleaved off from degraded sialoglycoconjugates are
      exported from lysosomes by a membrane transporter, named sialin, which is
      defective in two allelic inherited diseases: infantile sialic acid storage
      disease (ISSD) and Salla disease. To develop a functional assay of human sialin,
      we redirected the protein to the plasma membrane by mutating a dileucine-based
      internalization motif. Cells expressing the plasmalemmal construct accumulated
      neuraminic acid at acidic pH by a process equivalent to lysosomal efflux. The
      assay was used to determine how pathogenic mutations affect transport.
      Interestingly, while two missense mutations and one small, in-frame deletion
      associated with ISSD abolished transport, the mutation causing Salla disease
      (R39C) slowed down, but did not stop, the transport cycle, thus explaining why
      the latter disorder is less severe. Since neurological symptoms predominate in
      Salla disease, our results suggest that sialin is rate-limiting to specific
      sialic acid-dependent processes of the nervous system.

PMID- 15510213
TI  - E2Fs link the control of G1/S and G2/M transcription.
AB  - Previous work has provided evidence for E2F-dependent transcription control of
      both G1/S- and G2/M-regulated genes. Analysis of the G2-regulated cdc2 and cyclin
      B1 genes reveals the presence of both positive- and negative-acting E2F promoter
      elements. Additional elements provide both positive (CCAAT and Myb) and negative
      (CHR) control. Chromatin immunoprecipitation assays identify multiple
      interactions of E2F proteins that include those previously shown to activate and
      repress transcription. We find that E2F1, E2F2, and E2F3 bind to the positive
      acting E2F site in the cdc2 promoter, whereas E2F4 binds to the negative-acting
      site. We also find that binding of an activator E2F is dependent on an adjacent
      CCAAT site that is bound by the NF-Y transcription factor and binding of a
      repressor E2F is dependent on an adjacent CHR element, suggesting a role for
      cooperative interactions in determining both activation and repression. Finally,
      the kinetics of B-Myb interaction with the G2-regulated promoters coincides with
      the activation of the genes, and RNAi-mediated reduction of B-Myb inhibits
      expression of cyclin B1 and cdc2. The ability of B-Myb to interact with the cdc2
      promoter is dependent on an intact E2F binding site. These results thus point to
      a role for E2Fs, together with B-Myb, which is an E2F-regulated gene expressed at
      G1/S, in linking the regulation of genes at G1/S and G2/M.

PMID- 15510214
TI  - Three myosin V structures delineate essential features of chemo-mechanical
      transduction.
AB  - The molecular motor, myosin, undergoes conformational changes in order to convert
      chemical energy into force production. Based on kinetic and structural
      considerations, we assert that three crystal forms of the myosin V motor
      delineate the conformational changes that myosin motors undergo upon detachment
      from actin. First, a motor domain structure demonstrates that nucleotide-free
      myosin V adopts a specific state (rigor-like) that is not influenced by crystal
      packing. A second structure reveals an actomyosin state that favors rapid release
      of ADP, and differs from the rigor-like state by a P-loop rearrangement.
      Comparison of these structures with a third structure, a 2.0 angstroms resolution
      structure of the motor bound to an ATP analog, illuminates the structural
      features that provide communication between the actin interface and nucleotide
      binding site. Paramount among these is a region we name the transducer, which is
      composed of the seven-stranded beta-sheet and associated loops and linkers.
      Reminiscent of the beta-sheet distortion of the F1-ATPase, sequential distortion
      of this transducer region likely controls sequential release of products from the
      nucleotide pocket during force generation.

PMID- 15510215
TI  - Capicua integrates input from two maternal systems in Drosophila terminal
      patterning.
AB  - In Drosophila, the maternal terminal system specifies cell fates at the embryonic
      poles via the localised stimulation of the Torso receptor tyrosine kinase (RTK).
      Signalling by the Torso pathway relieves repression mediated by the Capicua and
      Groucho repressors, allowing the restricted expression of the zygotic terminal
      gap genes tailless and huckebein. Here we report a novel positive input into
      tailless and huckebein transcription by maternal posterior group genes,
      previously implicated in abdomen and pole cell formation. We show that absence of
      a subset of posterior group genes, or their overactivation, leads to the spatial
      reduction or expansion of the tailless and huckebein posterior expression
      domains, respectively. We demonstrate that the terminal and posterior systems
      converge, and that exclusion of Capicua from the termini of posterior group
      mutants is ineffective, accounting for reduced terminal gap gene expression in
      these embryos. We propose that the terminal and posterior systems function
      coordinately to alleviate transcriptional silencing by Capicua, and that the
      posterior system fine-tunes Torso RTK signalling output, ensuring precise spatial
      domains of tailless and huckebein expression.

PMID- 15510216
TI  - Autophosphorylation of ataxia-telangiectasia mutated is regulated by protein
      phosphatase 2A.
AB  - Ionizing radiation induces autophosphorylation of the ataxia-telangiectasia
      mutated (ATM) protein kinase on serine 1981; however, the precise mechanisms that
      regulate ATM activation are not fully understood. Here, we show that the protein
      phosphatase inhibitor okadaic acid (OA) induces autophosphorylation of ATM on
      serine 1981 in unirradiated cells at concentrations that inhibit protein
      phosphatase 2A-like activity in vitro. OA did not induce gamma-H2AX foci,
      suggesting that it induces ATM autophosphorylation by inactivation of a protein
      phosphatase rather than by inducing DNA double-strand breaks. In support of this,
      we show that ATM interacts with the scaffolding (A) subunit of protein
      phosphatase 2A (PP2A), that the scaffolding and catalytic (C) subunits of PP2A
      interact with ATM in undamaged cells and that immunoprecipitates of ATM from
      undamaged cells contain PP2A-like protein phosphatase activity. Moreover, we show
      that IR induces phosphorylation-dependent dissociation of PP2A from ATM and loss
      of the associated protein phosphatase activity. We propose that PP2A plays an
      important role in the regulation of ATM autophosphorylation and activity in vivo.

PMID- 15510217
TI  - Small proline-rich protein 1A is a gp130 pathway- and stress-inducible
      cardioprotective protein.
AB  - The interleukin-6 cytokines, acting via gp130 receptor pathways, play a pivotal
      role in the reduction of cardiac injury induced by mechanical stress or ischemia
      and in promoting subsequent adaptive remodeling of the heart. We have now
      identified the small proline-rich repeat proteins (SPRR) 1A and 2A as downstream
      targets of gp130 signaling that are strongly induced in cardiomyocytes responding
      to biomechanical/ischemic stress. Upregulation of SPRR1A and 2A was markedly
      reduced in the gp130 cardiomyocyte-restricted knockout mice. In cardiomyocytes,
      MEK1/2 inhibitors prevented SPRR1A upregulation by gp130 cytokines. Furthermore,
      binding of NF-IL6 (C/EBPbeta) and c-Jun to the SPRR1A promoter was observed after
      CT-1 stimulation. Histological analysis revealed that SPRR1A induction after
      mechanical stress of pressure overload was restricted to myocytes surrounding
      piecemeal necrotic lesions. A similar expression pattern was found in
      postinfarcted rat hearts. Both in vitro and in vivo ectopic overexpression of
      SPRR1A protected cardiomyocytes against ischemic injury. Thus, this study
      identifies SPRR1A as a novel stress-inducible downstream mediator of gp130
      cytokines in cardiomyocytes and documents its cardioprotective effect against
      ischemic stress.

PMID- 15510218
TI  - Crystal structure of ATF-2/c-Jun and IRF-3 bound to the interferon-beta enhancer.
AB  - Transcriptional activation of the interferon-beta (IFN-beta) gene requires
      assembly of an enhanceosome containing the transcription factors ATF-2/c-Jun, IRF
      3/IRF-7, NF-kappaB and HMGI(Y). These factors cooperatively bind a composite DNA
      site and activate expression of the IFN-beta gene. The 3.0 A crystal structure of
      the DNA-binding domains of ATF-2/c-Jun and two IRF-3 molecules in a complex with
      31 base pairs (bp) of the PRDIV-PRDIII region of the IFN-beta enhancer shows that
      association of the four proteins with DNA creates a continuous surface for the
      recognition of 24 bp. The structure, together with in vitro binding studies and
      protein mutagenesis, shows that protein-protein interactions are not critical for
      cooperative binding. Instead, cooperativity arises mainly through nucleotide
      sequence-dependent structural changes in the DNA that allow formation of
      complementary DNA conformations. Because the binding sites overlap on the
      enhancer, the unit of recognition is the entire nucleotide sequence, not the
      individual subsites.

PMID- 15510219
TI  - LAP2alpha and BAF collaborate to organize the Moloney murine leukemia virus
      preintegration complex.
AB  - Integration of viral DNA into the host genome is an essential step in retroviral
      replication. The viral DNA made by reverse transcription is a component of the
      preintegration complex (PIC) that also contains the viral integrase protein, the
      enzyme that integrates the viral DNA. Several other viral and cellular proteins
      are present in the PIC, but their functional roles are less well established.
      Barrier-to-autointegration factor (BAF) is a cellular protein component of the
      PIC that blocks autointegration of the viral DNA and stimulates intermolecular
      integration. In uninfected cells, BAF interacts with members of the LEM family of
      inner nuclear membrane and nucleoplasmic proteins. Here, we demonstrate that one
      of the LEM proteins, lamina-associated polypeptide 2alpha (LAP2alpha), is a
      component of the PIC. LAP2alpha stabilizes the association of BAF with the PIC to
      stimulate intermolecular integration and suppress autointegration. To further
      understand the role of LAP2alpha, we established LAP2alpha-knockdown cell lines.
      Depletion of LAP2alpha significantly inhibited viral replication. Our results
      demonstrate a critical contribution of LAP2alpha to the nucleoprotein
      organization of the PIC and to viral replication.

PMID- 15510220
TI  - alpha-Synuclein produces a long-lasting increase in neurotransmitter release.
AB  - Wild-type alpha-synuclein, a protein of unknown function, has received much
      attention because of its involvement in a series of diseases that are known as
      synucleinopathies. We find that long-lasting potentiation of synaptic
      transmission between cultured hippocampal neurons is accompanied by an increase
      in the number of alpha-synuclein clusters. Conversely, suppression of alpha
      synuclein expression through antisense nucleotide and knockout techniques blocks
      the potentiation, as well as the glutamate-induced increase in presynaptic
      functional bouton number. Consistent with these findings, alpha-synuclein
      introduction into the presynaptic neuron of a pair of monosynaptically connected
      cells causes a rapid and long-lasting enhancement of synaptic transmission, and
      rescues the block of potentiation in alpha-synuclein null mouse cultures. Also,
      we report that the application of nitric oxide (NO) increases the number of alpha
      synuclein clusters, and inhibitors of NO-synthase block this increase, supporting
      the hypothesis that NO is involved in the enhancement of the number of alpha
      synuclein clusters. Thus, alpha-synuclein is involved in synaptic plasticity by
      augmenting transmitter release from the presynaptic terminal.

PMID- 15510221
TI  - Genomic specification and epigenetic regulation of eukaryotic DNA replication
      origins.
AB  - Identification of DNA replication origins (ORIs) at a genome-wide level in
      eukaryotes has proved to be difficult due to the high degree of degeneracy of
      their sequences. Recent structural and functional approaches, however, have
      circumvented this limitation and have provided reliable predictions of their
      genomic distribution in the yeasts Saccharomyces cerevisiae and
      Schizosaccharomyces pombe, and they have also significantly increased the number
      of characterized ORIs in animals. This article reviews recent evidence on how
      ORIs are specified and maintained in these systems and on their regulation and
      sensitivity to epigenetic signals. It also discusses the possible additional
      involvement of ORIs in processes other than DNA replication.

PMID- 15510222
TI  - NO activation of guanylyl cyclase.
AB  - Nitric oxide (NO)-sensitive guanylyl-cyclase (GC) is the most important receptor
      for the signaling molecule NO. Activation of the enzyme is brought about by
      binding of NO to the prosthetic heme group. By monitoring NO-binding and
      catalytic activity simultaneously, we show that NO activates GC only if the
      reaction products of the enzyme are present. NO-binding in the absence of the
      products did not activate the enzyme, but yielded a nonactivated species with the
      spectral characteristics of the active form. Conversion of the nonactivated into
      the activated conformation of the enzyme required the simultaneous presence of NO
      and the reaction products. Furthermore, the products magnesium/cGMP/pyrophosphate
      promoted the release of the histidine-iron bond during NO-binding, indicating
      reciprocal communication of the catalytic and ligand-binding domains. Based on
      these observations, we present a model that proposes two NO-bound states of the
      enzyme: an active state formed in the presence of the products and a nonactivated
      state. The model not only covers the data reported here but also consolidates
      results from previous studies on NO-binding and dissociation/deactivation of GC.

PMID- 15510223
TI  - Histone hypomethylation is an indicator of epigenetic plasticity in quiescent
      lymphocytes.
AB  - Post-translational modifications of histone amino termini are thought to convey
      epigenetic information that extends the coding potential of DNA. In particular,
      histone lysine methylation has been implicated in conveying transcriptional
      memory and maintaining lineage fidelity. Here an analysis of histone lysine
      methylation in quiescent (G(0)) and cycling lymphocytes showed that methylation
      of histone H3 at lysines 4 (H3K4), 9 (H3K9), 27 (H3K27) and histone H4 at lysine
      20 is markedly reduced in resting B lymphocytes as compared with cycling cells.
      Quiescent B cells also lacked heterochromatin-associated HP1beta and Ikaros at
      pericentric chromatin and expressed low levels of Ezh2 and ESET histone methyl
      transferases (HMTases). Nuclei from resting B or T cells were approximately three
      times more efficiently reprogrammed in nuclear transfer assays than cells in
      which HMTase expression, histone methylation and HP1beta binding had been
      restored following mitotic stimulation. These results showing local and global
      changes in histone lysine methylation levels in vivo demonstrate that
      constitutive heterochromatin organization is modified in resting lymphocytes and
      suggest that histone hypomethylation is a useful indicator of epigenetic
      plasticity.

PMID- 15510224
TI  - Perception, action, and Roelofs effect: a mere illusion of dissociation.
AB  - A prominent and influential hypothesis of vision suggests the existence of two
      separate visual systems within the brain, one creating our perception of the
      world and another guiding our actions within it. The induced Roelofs effect has
      been described as providing strong evidence for this perception/action
      dissociation: When a small visual target is surrounded by a large frame
      positioned so that the frame's center is offset from the observer's midline, the
      perceived location of the target is shifted in the direction opposite the frame's
      offset. In spite of this perceptual mislocalization, however, the observer can
      accurately guide movements to the target location. Thus, perception is prone to
      the illusion while actions seem immune. Here we demonstrate that the Roelofs
      illusion is caused by a frame-induced transient distortion of the observer's
      apparent midline. We further demonstrate that actions guided to targets within
      this same distorted egocentric reference frame are fully expected to be accurate,
      since the errors of target localization will exactly cancel the errors of motor
      guidance. These findings provide a mechanistic explanation for the various
      perceptual and motor effects of the induced Roelofs illusion without requiring
      the existence of separate neural systems for perception and action. Given this,
      the behavioral dissociation that accompanies the Roelofs effect cannot be
      considered evidence of a dissociation of perception and action. This indicates a
      general need to re-evaluate the broad class of evidence purported to support this
      hypothesized dissociation.

PMID- 15510225
TI  - Representation of attended versus remembered locations in prefrontal cortex.
AB  - A great deal of research on the prefrontal cortex (PF), especially in nonhuman
      primates, has focused on the theory that it functions predominantly in the
      maintenance of short-term memories, and neurophysiologists have often interpreted
      PF's delay-period activity in the context of this theory. Neuroimaging results,
      however, suggest that PF's function extends beyond the maintenance of memories to
      include aspects of attention, such as the monitoring and selection of
      information. To explore alternative interpretations of PF's delay-period
      activity, we investigated the discharge rates of single PF neurons as monkeys
      attended to a stimulus marking one location while remembering a different,
      unmarked location. Both locations served as potential targets of a saccadic eye
      movement. Although the task made intensive demands on short-term memory, the
      largest proportion of PF neurons represented attended locations, not remembered
      ones. The present findings show that short-term memory functions cannot account
      for all, or even most, delay-period activity in the part of PF explored. Instead,
      PF's delay-period activity probably contributes more to the process of
      attentional selection.

PMID- 15510226
TI  - Unanticipated antigens: translation initiation at CUG with leucine.
AB  - Major histocompatibility class I molecules display tens of thousands of peptides
      on the cell surface for immune surveillance by T cells. The peptide repertoire
      represents virtually all cellular translation products, and can thus reveal a
      foreign presence inside the cell. These peptides are derived from not only
      conventional but also cryptic translational reading frames, including some
      without conventional AUG codons. To define the mechanism that generates these
      cryptic peptides, we used T cells as probes to analyze the peptides generated in
      transfected cells. We found that when CUG acts as an alternate initiation codon,
      it can be decoded as leucine rather than the expected methionine residue. The
      leucine start does not depend on an internal ribosome entry site-like mRNA
      structure, and its efficiency is enhanced by the Kozak nucleotide context.
      Furthermore, ribosomes scan 5' to 3' specifically for the CUG initiation codon in
      a eukaryotic translation initiation factor 2-independent manner. Because
      eukaryotic translation initiation factor 2 is frequently targeted to inhibit
      protein synthesis, this novel translation mechanism allows stressed cells to
      display antigenic peptides. This initiation mechanism could also be used at non
      AUG initiation codons often found in viral transcripts as well as in a growing
      list of cellular genes.

PMID- 15510227
TI  - Tuberculous granuloma formation is enhanced by a mycobacterium virulence
      determinant.
AB  - Granulomas are organized host immune structures composed of tightly interposed
      macrophages and other cells that form in response to a variety of persistent
      stimuli, both infectious and noninfectious. The tuberculous granuloma is
      essential for host containment of mycobacterial infection, although it does not
      always eradicate it. Therefore, it is considered a host-beneficial, if
      incompletely efficacious, immune response. The Mycobacterium RD1 locus encodes a
      specialized secretion system that promotes mycobacterial virulence by an unknown
      mechanism. Using transparent zebrafish embryos to monitor the infection process
      in real time, we found that RD1-deficient bacteria fail to elicit efficient
      granuloma formation despite their ability to grow inside of infected macrophages.
      We showed that macrophages infected with virulent mycobacteria produce an RD1
      dependent signal that directs macrophages to aggregate into granulomas. This
      Mycobacterium-induced macrophage aggregation in turn is tightly linked to
      intercellular bacterial dissemination and increased bacterial numbers. Thus,
      mycobacteria co-opt host granulomas for their virulence.

PMID- 15510228
TI  - The risk of a mosquito-borne infection in a heterogeneous environment.
AB  - A common assumption about malaria, dengue, and other mosquito-borne infections is
      that the two main components of the risk of human infection--the rate at which
      people are bitten (human biting rate) and the proportion of mosquitoes that are
      infectious--are positively correlated. In fact, these two risk factors are
      generated by different processes and may be negatively correlated across space
      and time in heterogeneous environments. Uneven distribution of blood-meal hosts
      and larval habitat creates a spatial mosaic of demograPhic sources and sinks.
      Moreover, mosquito populations fluctuate temporally, forced by environmental
      variables such as rainfall, temperature, and humidity. These sources of spatial
      and temporal heterogeneity in the distribution of mosquito populations generate
      variability in the human biting rate, in the proportion of mosquitoes that are
      infectious, and in the risk of human infection. To understand how heterogeneity
      affects the epidemiology of mosquito-borne infections, we developed a set of
      simple models that incorporate heterogeneity in a stepwise fashion. These models
      predict that the human biting rate is highest shortly after the mosquito
      densities peak, near breeding sites where adult mosquitoes emerge, and around the
      edges of areas where humans are aggregated. In contrast, the proportion of
      mosquitoes that are infectious reflects the age structure of mosquito
      populations; it peaks where old mosquitoes are found, far from mosquito breeding
      habitat, and when mosquito population density is declining. Finally, we show that
      estimates for the average risk of infection that are based on the average
      entomological inoculation rate are strongly biased in heterogeneous environments.

PMID- 15510230
TI  - Measuring global trends in the status of biodiversity: red list indices for
      birds.
AB  - The rapid destruction of the planet's biodiversity has prompted the nations of
      the world to set a target of achieving a significant reduction in the rate of
      loss of biodiversity by 2010. However, we do not yet have an adequate way of
      monitoring progress towards achieving this target. Here we present a method for
      producing indices based on the IUCN Red List to chart the overall threat status
      (projected relative extinction risk) of all the world's bird species from 1988 to
      2004. Red List Indices (RLIs) are based on the number of species in each Red List
      category, and on the number changing categories between assessments as a result
      of genuine improvement or deterioration in status. The RLI for all bird species
      shows that their overall threat status has continued to deteriorate since 1988.
      Disaggregated indices show that deteriorations have occurred worldwide and in all
      major ecosystems, but with particularly steep declines in the indices for Indo
      Malayan birds (driven by intensifying deforestation of the Sundaic lowlands) and
      for albatrosses and petrels (driven by incidental mortality in commercial
      longline fisheries). RLIs complement indicators based on species population
      trends and habitat extent for quantifying global trends in the status of
      biodiversity. Their main weaknesses are that the resolution of status changes is
      fairly coarse and that delays may occur before some status changes are detected.
      Their greatest strength is that they are based on information from nearly all
      species in a taxonomic group worldwide, rather than a potentially biased subset.
      At present, suitable data are only available for birds, but indices for other
      taxonomic groups are in development, as is a sampled index based on a stratified
      sample from all major taxonomic groups.

PMID- 15510229
TI  - Motifs in brain networks.
AB  - Complex brains have evolved a highly efficient network architecture whose
      structural connectivity is capable of generating a large repertoire of functional
      states. We detect characteristic network building blocks (structural and
      functional motifs) in neuroanatomical data sets and identify a small set of
      structural motifs that occur in significantly increased numbers. Our analysis
      suggests the hypothesis that brain networks maximize both the number and the
      diversity of functional motifs, while the repertoire of structural motifs remains
      small. Using functional motif number as a cost function in an optimization
      algorithm, we obtain network topologies that resemble real brain networks across
      a broad spectrum of structural measures, including small-world attributes. These
      results are consistent with the hypothesis that highly evolved neural
      architectures are organized to maximize functional repertoires and to support
      highly efficient integration of information.

PMID- 15510231
TI  - Ciclesonide: a novel inhaled corticosteroid for asthma.
AB  - The adoption of inhaled corticosteroids for the treatment of asthma has resulted
      in significant improvements in asthma symptoms and pulmonary function, and has
      reduced the incidence of asthma exacerbations, emergency room visits and
      hospitalizations. Although inhaled corticosteroids are generally safe and well
      tolerated compared with oral corticosteroids, concerns remain about potential
      side effects. Clinically significant complications include local effects such as
      dysphonia and oral candidiasis and potentially serious systemic effects
      associated with cortisol suppression including growth retardation, glucose
      intolerance and increased risk for osteoporosis and fractures. These side effects
      are more likely to occur with long-term use and are dose related. Over the years,
      attempts have been made to develop corticosteroids with potent local
      antiinflammatory activity and an improved safety profile. Ciclesonide ([R]-11
      beta,16 alpha,17,21-tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16,17-acetal
      with cyclohexanecarboxaldehyde 21-isobutyrate) was designed to achieve these
      objectives. Ciclesonide is a parent compound that is converted locally in airways
      by esterases to produce the active metabolite, desisobutyryl-ciclesonide (des
      CIC). The active metabolite, des-CIC, has a 100-fold greater relative
      glucocorticoid receptor binding affinity than ciclesonide itself (relative
      glucocorticoid receptor binding affinities are 1200 and 12, respectively;
      dexamethasone reference is 100). If any ciclesonide enters the circulation, it is
      highly protein bound (99%) and extensively metabolized by liver oxidases,
      resulting in very low systemic exposure. Ciclesonide is delivered in solution
      form via a hydrofluoroalkane metered-dose inhaler (MDI) with a once-daily dosing
      schedule, which facilitates patient compliance. Clinical studies demonstrate that
      ciclesonide is as effective as existing "gold standard" inhaled corticosteroids
      for control of asthma and has a good safety profile.

PMID- 15510232
TI  - Genes and migraine.
AB  - Migraine is not a disease but a syndrome that undoubtedly has multiple causes.
      Several migraine syndromes have a clear autosomal dominant pattern of
      inheritance, and recently, mutations have been found in two different genes in
      families with hemiplegic migraine. Familial aggregation and twin studies in
      families with other more common migraine syndromes (i.e., migraine without aura
      and migraine with aura) show that genetic factors are important, although the
      mode of inheritance is not always clear. Numerous candidate genes have been
      identified based on clinical features of migraine and the known functions of the
      different genes. Recently genome-wide scans in families with migraine without
      aura and migraine with aura have identified susceptibility loci for these common
      syndromes. However, none of the numerous studies performed to date provide
      convincing evidence for a gene responsible for the common varieties of migraine.

PMID- 15510233
TI  - Evaluation of oral budesonide in the treatment of active distal ulcerative
      colitis.
AB  - Budesonide, a topical corticosteroid, has proven useful for the management of
      Crohn's disease. Its efficacy is similar to prednisone but it has fewer side
      effects. A new pH-modified release capsule (Budenofalk) is probably efficacious
      in distal ulcerative colitis. The aim of the present study was to establish the
      pharmacokinetics, pharmacodynamics, and safety of two dosage regimens of
      budesonide capsules and to obtain efficacy information. Budenofalk 9 mg daily was
      administered as a single dose 9 mg in 8 patients and as three 3 mg doses in 7
      patients with active distal ulcerative colitis for 8 weeks. Symptoms were
      assessed at three timepoints during the study: baseline, 4 and 8 weeks after
      start of treatment. Endoscopic evaluation and budesonide concentration in mucosal
      biopsy specimens was performed at 0 and 8 weeks. A pharmacokinetic profile and
      pharmacodynamic profile (cortisol, lymphocytes and neutrophils) was performed at
      day 5. In the 9 mg o.d. group, higher peak concentrations and systemic
      availability was found compared to the 3 mg t.i.d. group. Cortisol suppression
      was more pronounced after 9 mg o.d. than after 3 mg t.i.d. Lag-time, AUC and
      pharmacodynamic effects were comparable (14% mean decrease lymphocyte count and
      26% mean increase neutrophil count). Mucosal biopsy specimens in the distal colon
      revealed significant budesonide levels with both regimens. After 8 weeks, 71% in
      the 9 mg o.d. group and 38% in the 3 t.i.d. group responded. The endoscopic index
      improved from 10 +/- 2 to 2 +/- 3 (p <0.001) with 9 mg o.d. and from 9 +/- 2 to 4
      +/- 4.7 (p = 0.02) with 3 mg t.i.d. The pharmacokinetic and pharmacodynamic
      profiles found in this study indicate that Budenofalk reaches the distal part of
      colon and rectum, but further studies to validate the budesonide assay in the
      mucosa and comparison with a control group are necessary. This limited study
      suggests that Budenofalk is effective in distal colitis and side effects are
      rare. Based on these observations a large clinical trial using 9 mg o.d. is
      indicated to confirm efficacy and assess further possible side effects.

PMID- 15510234
TI  - Anticonvulsant drugs in the treatment of substance withdrawal.
AB  - Although detoxification cannot, in itself, be considered a treatment for
      addiction, it is one of the most pivotal phases. In order to facilitate entry
      into recovery and/or rehabilitation programs, a detoxification treatment has to
      be experienced as easy and safe by the patient. In consideration of the many
      inconveniences related to standard withdrawal treatments, there is an interest in
      developing alternative pharmacological strategies. The main rationales for using
      anticonvulsants in substance-abuse patients are their lack of addiction
      potential, evidence support a role of kindling mechanisms in withdrawal syndromes
      and their efficacy in comorbid psychiatric disorders. The available data
      currently support the utilization of carbamazepine as a treatment for
      detoxification from benzodiazepines, alcohol and opiates, and as a useful agent
      to reduce cocaine consumption. The use of valproate is well corroborated for
      alcohol detoxification and it seems to be a promising treatment for the reduction
      of cocaine use; however, it has been found to be ineffective against
      benzodiazepine withdrawal symptoms. Some preliminary data suggest that
      lamotrigine could be useful in opiate and cocaine dependence. Gabapentin shows
      potential as a treatment for cocaine dependence, and some case reports have
      stimulated interest in this agent for alcohol and benzodiazepine detoxification.
      Due to its particular pharmacological profile, topiramate is one of the most
      interesting newer anticonvulsants. It has been found to be efficacious in opiate
      and possibly benzodiazepine detoxification and also has theoretical potential as
      a preventive therapy.

PMID- 15510235
TI  - Recent developments in lipid-lowering therapy. Highlights from the Atorvastatin
      Landmark Program: Global Investigators Meeting III. June 1-3, 2004. Toronto,
      Canada.
AB  - The Atorvastatin Landmark Program: Global Investigators Meeting III was held June
      1-3, in Toronto, Canada. The purpose of the meeting was to update investigators
      on the current status of the clinical trials that encompass the Atorvastatin
      Landmark Program. The main objectives were the following: 1. To review the range
      of studies that comprise the Atorvastatin Landmark Program. 2. To communicate
      recently completed study results and discuss the current and future impact of the
      findings, both individually and collectively, on clinical practice and guideline
      recommendations. 3. To discuss how the program is anticipated to evolve,
      highlighting new therapeutic modalities.

PMID- 15510236
TI  - Rosiglitazone maleate/metformin hydrochloride: a new formulation therapy for type
      2 diabetes.
AB  - Many patients with type 2 diabetes require treatment with more than one
      antihyperglycemic drug to achieve optimal glycemic control. The
      thiazolidinediones are a novel class of oral antihyperglycemic drugs that improve
      glycemic control primarily by increasing peripheral insulin resistance and
      sensitizing the skeletal muscle, liver and adipose tissue to the actions of
      insulin, in addition to improving beta-cell function. One of the many features of
      the thiazolidinedione class of drugs is their synergism with other
      antihyperglycemic drugs that have a different mechanism of action. The
      combination of metformin hydrochloride, a biguanide that enhances glucose uptake
      in peripheral tissues and reduces hepatic gluconeogenesis, with rosiglitazone
      maleate, one of the newly available members of the thiazolidinedione family,
      offers a rational therapeutic approach to the treatment of type 2 diabetes. In
      patients whose type 2 diabetes is inadequately controlled with metformin
      monotherapy, the addition of rosiglitazone significantly improves glycemic
      control, insulin sensitivity and beta-cell function, compared with either drug
      alone. In addition, this combination therapy has beneficial effects on other
      cardiovascular risk factors. Rosiglitazone maleate/metformin hydrochloride
      combination therapy is well tolerated in patients with type 2 diabetes and has a
      favorable safety profile. This review summarizes the available evidence on the
      clinical efficacy and safety of rosiglitazone maleate and metformin hydrochloride
      combination therapy in patients with type 2 diabetes.

PMID- 15510237
TI  - Dutasteride: a potent dual inhibitor of 5-alpha-reductase for benign prostatic
      hyperplasia.
AB  - Dutasteride is a 5alpha-reductase inhibitor that inhibits both types 1 and 2
      isozymes of 5alpha-reductase, the enzyme responsible for converting testosterone
      to dihydrotestosterone in the prostate and other tissues. Dihydrotestosterone is
      the primary cause of prostate growth and has been proven to play a key role in
      the development and progression of benign prostatic hyperplasia. Dutasteride has
      been investigated in three multicenter studies involving 4325 men aged 50 years
      and above with benign prostatic hyperplasia. Data from these two-year, placebo
      controlled studies demonstrated that dutasteride 0.5 mg once daily reduced the
      risk of both acute urinary retention and the need for benign prostatic
      hyperplasia-related surgical intervention, improved benign prostatic hyperplasia
      related symptoms, decreased prostate volume and increased maximum urinary flow
      rates with a low incidence of generally mild to moderate adverse events.

PMID- 15510238
TI  - Towards cannabis and cannabinoid treatment of multiple sclerosis.
AB  - Multiple sclerosis is a common human demyelinating disease of the central nervous
      system (CNS), and it is thought to involve autoimmune responses to CNS myelin
      antigens. Current symptomatic therapies for multiple sclerosis are in some cases
      ineffective and may have a high risk of serious side effects. This has led some
      multiple sclerosis patients to self-medicate with cannabis, which anecdotal
      evidence suggests may be beneficial in controlling symptoms such as spasticity,
      pain, tremor and bladder dysfunction. In support of these claims, results from
      experimental studies have suggested that cannabinoid-based treatments may be
      beneficial in a wide number of diseases. Furthermore, recent research in animal
      models of multiple sclerosis has demonstrated the efficacy of cannabinoids in
      controlling disease-induced symptoms such as spasticity and tremor, as well as in
      ameliorating the severity of clinical disease. However, these initially promising
      results have not yet been fully translated into the clinic. Although cannabinoid
      treatment of multiple sclerosis symptoms has been shown to be both well tolerated
      and effective in a number of subjective tests in several small-scale clinical
      trials, objective measures demonstrating the efficacy of cannabinoids are still
      lacking. Currently, a number of large-scale phase III clinical trials are under
      way to further elucidate the use of cannabinoids in the symptomatic treatment of
      multiple sclerosis. This review highlights the recent advances in our
      understanding of the endocannabinoid system, discusses both the experimental and
      clinical evidence for the use of cannabinoids to treat multiple sclerosis and
      explores possible future strategies of cannabinoid therapy in multiple sclerosis.

PMID- 15510239
TI  - Epinastine hydrochloride for atopic disease.
AB  - Atopic conditions include allergic rhinitis, atopic eczema, allergic
      conjunctivitis and asthma. Doctors and patients can choose from a variety of
      antiallergy medications, testifying that no one medication will suffice to treat
      all symptoms and that each has a different side-effect profile. Antiallergy
      medications target histamine receptors, as histamine release contributes to the
      unpleasant symptoms of itching, tearing, runny nose and skin urticaria. The ideal
      antihistamine would control the symptoms of atopic disease but cause very few
      side effects. Traditionally, unwanted effects include drowsiness and somnolence
      due to CNS depression, and digestive tract problems such as loss of appetite,
      nausea, vomiting and constipation or diarrhea. Some antihistamines also have
      anticholinergic effects that are mediated by muscarinic receptors. These atropine
      like actions, which can affect the cardiovascular system, are sufficiently
      prominent in some drugs to be manifest during clinical usage. Epinastine
      hydrochloride minimally penetrates the blood/brain barrier and has almost no
      effect on the muscarinic receptors. This drug is marketed as having very few CNS
      depressant side effects, few drug interactions and gastrointestinal side effects,
      and a low risk of cardiotoxicity.

PMID- 15510240
TI  - Memantine hydrochloride: pharmacological and clinical profile.
AB  - Memantine (Axura, Merz Pharmaceuticals GmbH; Ebixa, H. Lundbeck A/S, Namenda,
      Forest Laboratories, Inc.) is an uncompetitive N-methyl-D-aspartate (NMDA)
      receptor antagonist with low to moderate affinity for the (+)MK-801 binding site.
      It is characterized as a voltage-sensitive open-channel NMDA receptor blocker
      that antagonizes NMDA receptor-mediated inward currents in vitro with an IC50 of
      1-3 microM. In animal models, memantine displays both neuroprotective
      (antiexcitotoxic) and cognition-enhancing properties at therapeutically relevant
      concentrations. The strong voltage dependency and rapid blocking/unblocking
      kinetics of memantine are thought to be the basis for its excellent clinical
      tolerability. Recently completed clinical studies demonstrate positive effects of
      memantine in Alzheimer's disease both as a monotherapy and in patients receiving
      continuous donepezil treatment. Memantine treatment also has demonstrated
      significant improvement of cognitive performance in patients suffering from
      vascular dementia. Furthermore, the safety and tolerability of memantine in
      clinical trials has been excellent, with the incidence of premature withdrawals
      due to adverse events no greater than placebo and overall low frequencies of
      total adverse events. In 2002, memantine was approved by the European Medicines
      Agency (EMEA) for the treatment of moderately severe to severe Alzheimer's
      disease. More recently, memantine was approved in the US for the treatment of
      moderate to severe Alzheimer's disease (October 2003). Here, we review the most
      recent pharmacological and clinical data in dementia patients that has emerged
      from the systematic evaluation of memantine.

PMID- 15510241
TI  - Systemic treatment of advanced non-small cell lung cancer.
AB  - Lung cancer, a highly lethal malignancy, is the leading cause of cancer-related
      mortality in the US, accounting for 28% of all deaths related to cancer. Non
      small cell lung cancer comprises 80-85% of lung cancer diagnoses and includes the
      histologies of adenocarcinoma and its subtype bronchoalveolar carcinoma, squamous
      cell carcinoma and large cell carcinoma. This article reviews the use of
      cytotoxic chemotherapies and other systemic treatments for patients with advanced
      (metastatic and/or recurrent) non-small cell lung cancer. Despite great efforts,
      only minor gains have been made over the past decade in the treatment of advanced
      non-small cell lung cancer for patients with a good performance status in terms
      of prolonging survival and improving quality of life. Currently, the standard of
      treatment is a platinum-based doublet, with the second agent being selected
      contingent upon the comorbidities of the patient and the toxicity profile of the
      drug. The focus of clinical research is centered on the application of the use of
      targeted, molecularly directed therapies, likely used in combination with either
      cytotoxics and/or other novel targeted agents, in an attempt to improve the
      therapeutic ratio of systemic treatments for this large population.

PMID- 15510242
TI  - Butyrylcholinesterase, cholinergic neurotransmission and the pathology of
      Alzheimer's disease.
AB  - Butyrylcholinesterase is a serine hydrolase biochemically related to the
      cholinergic enzyme acetylcholinesterase. It is capable of hydrolyzing esters of
      choline. Butyrylcholinesterase has unique enzymatic properties and is widely
      distributed in the nervous system, raising the possibility of its involvement in
      neural function. In particular, recent evidence indicates that along with
      acetylcholinesterase, butyrylcholinesterase catalyzes the hydrolysis of
      acetylcholine, and thus serves as a co-regulator of cholinergic transmission.
      Accumulating evidence also indicates that butyrylcholinesterase is likely to be
      involved in neurodegenerative disorders such as Alzheimer's disease. Therefore,
      inhibition of butyrylcholinesterase will not only lead to enhanced cholinergic
      transmission but also has the potential to interfere with the disease process in
      Alzheimer's disease and other dementing disorders.

PMID- 15510243
TI  - Cancer gene therapy based on the abstracts of the 2003 ASCO meeting and recent
      publications.
AB  - Abstracts concerning different target genes identified for cancer gene therapy
      and presented at the 2003 Meeting of the American Society of Clinical Oncology
      (ASCO) are summarized in this article.

PMID- 15510244
TI  - Canadian normal lung function values.

PMID- 15510245
TI  - Membership survey results.

PMID- 15510246
TI  - Seasonal fluctuations in airway responsiveness in elite endurance athletes.
AB  - BACKGROUND: It has been suggested that exposure to winter training conditions
      (irritants in indoor facilities and/or cold, dry air in the outdoors) can
      increase airway responsiveness in elite endurance athletes. OBJECTIVES: It has
      yet to be elucidated whether elite endurance athletes experience seasonal
      fluctuations in their airway responsiveness. METHODS: Eighteen members of a
      varsity cross-country running team underwent screening procedures and five
      members were enrolled in the study. Each athlete completed a respiratory and
      training questionnaire, and underwent allergy skin prick testing. Airway
      responsiveness was evaluated using a methacholine challenge on four occasions.
      RESULTS: The participants demonstrated a significant (more than twofold) increase
      in airway responsiveness (P=0.0496) during the first winter evaluation compared
      with the autumn baseline. The second winter evaluation still showed an increase
      but it was not statistically significant. Airway responsiveness had returned to
      baseline (autumn) values at spring testing. CONCLUSION: Elite endurance athletes
      experience seasonal fluctuations in airway responsiveness. The specific stimuli
      that cause this are unknown, but it is speculated to be due to exposure to cold,
      dry air and/or inhaled irritants that may be present in indoor training
      facilities.

PMID- 15510247
TI  - Comparative prevalence of asthma in different groups of athletes: a survey.
AB  - BACKGROUND: The type of air predominantly inhaled during training seems to play
      an important role in the development of airway hyperresponsiveness in athletes;
      however, this factor has not been evaluated for asthma. OBJECTIVE AND PATIENTS:
      To compare the prevalence of self-reported and/or physician-diagnosed asthma
      among four groups of athletes categorized according to the type of air
      predominantly inhaled during training: cold air (n=176), dry air (n=384), humid
      air (n=95), and mixed dry and humid air (n=43). METHOD: Self-administrated
      questionnaires were used. RESULTS: One hundred seven (15.3%) of the 698 athletes
      reported having asthma; of these 107 athletes, 92 had physician-diagnosed asthma.
      No significant differences were found for the prevalence of asthma: 15.9% (cold
      air), 15.4% (dry air), 12.6% (humid air) and 18.6% (mixed dry and humid air),
      respectively (P>0.05). Furthermore, no significant differences were observed
      among the groups for the prevalence of confirmed atopy, cold/flu or respiratory
      infections (all P>0.05), except for the prevalence of hay fever, which was
      significantly lower among athletes of the dry air group (P=0.04). Athletes having
      a first-degree relative with asthma did not have a higher prevalence of asthma
      than those who did not (P>0.05). CONCLUSION: The prevalence of asthma was not
      significantly different among the four groups of athletes and it was not
      associated with a family history of asthma.

PMID- 15510248
TI  - Pulmonary rehabilitation improves functional capacity in patients 80 years of age
      or older.
AB  - OBJECTIVES: There is limited evidence that pulmonary rehabilitation improves
      exercise capacity in older patients with chronic respiratory disease. The
      objective of the present study was to determine whether patients 80 years of age
      or older gain similar benefits from pulmonary rehabilitation as do younger
      patients. DESIGN: Outcomes were compared in 230 consecutive inpatients with
      moderate to severe lung disease who participated in a comprehensive pulmonary
      rehabilitation program during a one-year period. Outcomes included 6 min walk
      test distance (6MWT), the number of stairs completed in 2 min (2MST), Borg
      dyspnea scores after exertion and objective functional scores. RESULTS: There
      were no differences between older (80 to 91 years, n=43) and younger patients
      (n=187) with respect to sex, forced expiratory volume in 1 s (mean 0.77 L versus
      0.72 L) or number of chronic medical diagnoses (2.4 versus 2.7). Older patients
      were less frequently survivors of mechanical ventilation (2.3% versus 16%).
      Baseline 6MWT (133 m versus 144 m; P=0.48) and 2MST (5.2 laps versus 6.5 laps;
      P=0.067) were similar but global function was lower (85 versus 89; P=0.040) in
      older patients than in younger patients, respectively. After pulmonary
      rehabilitation, all outcomes improved significantly regardless of age (all before
      after comparisons P<0.0001). Younger patients improved with a higher discharge
      6MWT (231 m versus 185 m; P=0.004) and similar discharge 2MST (9.3 laps versus
      7.9 laps; P=0.070) compared with older patients. Global function at discharge
      remained lower in older patients than younger patients (91 versus 94; P=0.002).
      The duration of rehabilitation and length of stay were similar between the two
      groups. CONCLUSION: A comprehensive inpatient pulmonary rehabilitation program is
      beneficial in selected patients 80 years of age or older.

PMID- 15510249
TI  - Reference values of pulmonary function tests for Canadian Caucasians.
AB  - A multicentre, cross-sectional study was carried out in six centres across Canada
      to establish a national standard for pulmonary function tests using healthy,
      lifetime nonsmokers, with each centre aiming to test 10 men and 10 women from
      each decade from 20 to 80 years of age. Data from each centre were used to derive
      prediction equations for each centre, and pooled data from all centres (total:
      327 women and 300 men) were used to derive Canadian predicted equations. The
      predictive models were compared with three widely used published models for
      selected tests. It was found that, in general, the equations modelled for each
      centre could be replaced by the models obtained when pooling all data (Canadian
      model). Comparisons with the published references showed good agreement and
      similar slopes for most tests. The results suggest that pulmonary function test
      results obtained from different centres in Canada were comparable and that
      standards currently used remain valid for Canadian Caucasians.

PMID- 15510250
TI  - Cartography of emergency department visits for asthma - targeting high-morbidity
      populations.
AB  - BACKGROUND: Asthma education should be offered with priority to populations with
      the highest asthma-related morbidity. In the present study, the aim was to
      identify populations with high-morbidity for asthma from the Quebec Health
      Insurance Board Registry, a large administrative database, to help the Quebec
      Asthma and Chronic Obstructive Pulmonary Disease Network target its
      interventions. METHODS: All emergency department (ED) visits for asthma were
      analyzed over a one-year period, considering individual and medical variables.
      Age- and sex-adjusted rates, as well as standardized rate ratios related to the
      overall Quebec rate, among persons zero to four years of age and five to 44 years
      of age were determined for 15 regions and 163 areas served by Centres Locaux de
      Services Communautaires (CLSC). The areas with rates 50% to 300% higher (P<0.01)
      than the provincial rate were defined as high-morbidity areas. Maps of all CLSC
      areas were generated for the above parameters. RESULTS: There were 102,551 ED
      visits recorded for asthma, of which more than 40% were revisits. Twenty-one
      CLSCs and 32 CLSCs were high-morbidity areas for the zero to four years age group
      and five to 44 years age group, respectively. For the most part, the high
      morbidity areas were located in the south-central region of Quebec. Only 47% of
      asthmatic patients seen in ED had also seen a physician in ambulatory care.
      CONCLUSION: The data suggest that a significant portion of the population seeking
      care at the ED is undiagnosed and undertreated. A map of high-morbidity areas
      that could help target interventions to improve asthma care and outcomes is
      proposed.

PMID- 15510251
TI  - Video-assisted thoracoscopic lung biopsy as a possible cause of acute
      interstitial pneumonia in a patient with nonspecific interstitial pneumonia.
AB  - The present case report describes a 44-year-old woman who presented with dyspnea
      due to diffuse interstitial lung disease. High-resolution computed tomography
      showed features of usual interstitial pneumonia, but the lung biopsy obtained by
      video-assisted thoracoscopy was consistent with a histological pattern of
      nonspecific interstitial pneumonia. Following the procedure, the patient
      developed progressive respiratory distress and died on postoperative day 13 with
      a clinical picture of acute interstitial pneumonia. The autopsy showed evidence
      of diffuse alveolar damage superimposed on the background pattern of nonspecific
      interstitial pneumonia. The present case report supports the notion that patients
      with a variety of subtypes of idiopathic interstitial pneumonias may be at risk
      of exacerbation of their underlying disease following thoracic procedures,
      including video-assisted thoracoscopic lung biopsy.

PMID- 15510252
TI  - Interferon treatment of multiple pulmonary malignancies associated with papilloma
      virus.
AB  - Over a period of four years, beginning in spring 1988, a previously healthy man
      developed a primary squamous cell carcinoma of the tonsil, treated with
      radiotherapy, followed by 10 distinct, primary bronchial squamous cell
      carcinomas. Four of the cancers were surgically resected, all of which were
      positive by hybridization for human papilloma virus (type 16). Following the
      institution of alpha interferon, three smaller lesions disappeared and a larger
      one shrank in size, facilitating surgical resection. Over the following seven
      years no new ones have appeared. The finding of papilloma virus in malignancies
      should prompt consideration of antiviral therapy.

PMID- 15510253
TI  - Iodide effects in transition metal catalyzed reactions.
AB  - The unique properties of I(-) allow it to be involved in several different ways
      in reactions catalyzed by the late transition metals: in the oxidative addition,
      the migration, and the coupling/reductive elimination steps, as well as in
      substrate activation. Most steps are accelerated by I(-)(for example through an
      increased nucleophilicity of the metal center), but some are retarded, because a
      coordination site is blocked. The "soft" iodide ligand binds more strongly to
      soft metals (low oxidation state, electron rich, and polarizable) such as the
      later and heavier transition metals, than do the other halides, or N- and O
      centered ligands. Hence in a catalytic cycle that includes the metal in a
      formally low oxidation state there will be less tendency for the metal to
      precipitate (and be removed from the cycle) in the presence of I(-) than most
      other ligands. Iodide is a good nucleophile and is also easily and reversibly
      oxidized to I(2). In addition, I(-) can play key roles in purely organic
      reactions that occur as part of a catalytic cycle. Thus to understand the
      function of iodide requires careful analysis, since two or sometimes more effects
      occur in different steps of one single cycle. Each of these topics is illustrated
      with examples of the influence of iodide from homogeneous catalytic reactions in
      the literature: methanol carbonylation to acetic acid and related reactions; CO
      hydrogenation; imine hydrogenation; and C-C and C-N coupling reactions. General
      features are summarised in the Conclusions.

PMID- 15510254
TI  - Endohedral nickel and palladium atoms in metal clusters: analogy to endohedral
      noble gas atoms in fullerenes in polyhedra with five-fold symmetry.
AB  - Nickel and palladium atoms with their closed-shell d(10) electronic
      configurations are encapsulated in the icosahedral clusters
      [Ni@Ni(10)E(2)(CO)(18)](4-)(E = Sb, Bi, Sb[rightward arrow]Ni(CO)(3), CH(3)Sn and
      n-C(4)H(9)Sn) and the geometrically related pentagonal antiprismatic cluster
      Pd@Bi(10)(4+) found in Bi(14)PdBr(16). Such endohedral d(10) atoms in pentagonal
      antiprismatic clusters are donors of zero skeletal electrons and interact only
      weakly with the atoms in the surrounding polyhedron so that they may be regarded
      as analogous to endohedral noble gases in fullerenes such as He@C(60). On the
      other hand, endohedral nickel and palladium atoms in 10- and 11-vertex flattened
      deltahedral bare metal clusters of group 13 metals without five-fold symmetry,
      such as Ni@E(10)(10-) found in Na(10)NiE(10)(E = Ga, In) and Pd@Tl(11)(7-) found
      in A(8)Tl(11)Pd (A = Cs, Rb, K), interact significantly with the cluster atoms,
      particularly those at the flattened vertices of the deltahedron. The role of
      endohedral d(10) atoms Ni and Pd in polyhedra with five-fold symmetry as "pseudo
      noble-gases" can be related to their positions at the "composite divide" of the
      "Metallurgists' Periodic Table" proposed by H. E. N. Stone on the basis of alloy
      systematics as well as the equivalence of the five d orbitals in polyhedra with
      five-fold symmetry.

PMID- 15510255
TI  - The origin of chemoselectivity in the hydrocarbonylation of alkenes catalysed by
      trialkylphosphine complexes of rhodium.
AB  - The formation of monophosphine acyl intermediates explains why PPr(i)(3) and
      PBu(i)(3) generate aldehydes in alkene hydrocarbonylation reactions carried out
      in protic solvents, whilst PEt(3), for which the acyl complex contains two
      phosphines, produces alcohols.

PMID- 15510256
TI  - Neutral and zwitterionic group 4 metal alkyls with ancillary boroxide ligands.
AB  - The boroxide anion, [OB(mes)(2)](-), has been applied as an ancillary ligand to
      generate electron-deficient group 4 metal alkyls; however, the enhanced
      electrophilicity results in formation of tight ion-pairs in solution.

PMID- 15510257
TI  - Chromium(III) and chromium(IV) bis(trimethylsilyl)amido complexes as ethylene
      polymerisation catalysts.
AB  - Oxidation of Cr[N(SiMe(3))(2)](2)(THF)(2) with iodine and dicumyl peroxide
      results in tetrahedral Cr(iv) Cr[N(SiMe(3))(2)](2)I(2) and trigonal planar
      Cr(iii) Cr[N(SiMe(3))(2)](OCMe(2)Ph)(2), respectively; both complexes have been
      characterised by single-crystal X-ray diffraction, and both are active for
      ethylene polymerisation with alkylaluminium co-catalysts.

PMID- 15510258
TI  - Synthesis and magnetic behavior of the tetrahedral cage complex
      [(cyclen)4V4(CN)6]6+.
AB  - Reaction of [(cyclen)V(CF(3)SO(3))(2)](CF(3)SO(3)) with 4 equiv. of Et(4)N(CN) in
      DMF generates the seven-coordinate complex [(cyclen)V(CN)(3)], while a reaction
      employing just 1.5 equiv. produces a tetrahedral cage complex,
      [(cyclen)(4)V(4)(CN)(6)](6+), in which antiferromagnetic coupling leads to an S=
      0 ground state.

PMID- 15510259
TI  - In situ formation of meso-2,2'-oxydisuccinate via intermolecular dehydration
      coupling of D,L-malic acid: first coordination polymer of 2,2'-oxydisuccinate
      involving ether oxygen coordination: [Cd2(meso-odsc)(H2O)].
AB  - The first coordination polymer of 2,2'-oxydisuccinate, [Cd(2)(meso
      odsc)(H(2)O)](odsc =meso-2,2'-oxydisuccinate), was hydrothermally synthesized
      from CdSO(4) and D,L-malic acid; X-ray crystallography shows that the D,L-malic
      acid was transformed in situ into meso-odsc via intermolecular dehydration
      coupling.

PMID- 15510260
TI  - The ligand, the metal and the 'Holey'-host: Synthesis, structural and magnetic
      characterisation of Co(II), Ni(II) and Mn(II) metal-organic frameworks
      incorporating 4,4'-dicarboxy-2,2'-bipyridine.
AB  - We report herein the single crystal structures of four metal-organic framework
      complexes incorporating the 4,4'-dicarboxy-2,2'-bipyridine ligand, H(2)dcbp:
      alpha-[Co(dcbp)(H(2)O)(2)], 1; beta-[Co(dcbp)(H(2)O)(2)], 2,
      [Ni(dcbp)(H(2)O)(2)], and [[Mn(dcbp)].1/2DEF], 4 (DEF = diethylformamide). In
      each complex the ligand is deprotonated giving neutral species with 1:1
      stoichiometry that form three-dimensional coordination polymers. Supramolecular
      isomerism (polymorphism) in 1 and 2 arises from the different ligand connectivity
      around the octahedral Co(II) centres. The two coordinated water molecules in 1
      occupy cis positions, which are trans to the chelating bipyridine nitrogen atoms,
      leaving the carboxylate oxygen atoms in axial trans positions. In 2 all like
      donors occupy cis positions. Different modes of carboxylate coordination in 1 and
      2 give dissimilar network topologies. A rare example of two interpenetrating
      6(4)8(2)-b (quartz-like) chiral networks in 1 results from both dcbp carboxylate
      groups coordinating in a monodentate fashion to adjacent Co(II) centres, whereas
      in 2 only one carboxylate group bridges between adjacent Co(II) centres giving
      rise to a single chiral (10,3)-a net. In 1 and 2 the coordinated water molecules
      hydrogen bond to the non-coordinated carboxylate oxygen atoms. These interactions
      give rise to water-carboxylate double helices in , and support the coordination
      network in 2. Strikingly for a pair of dimorphs the crystal densities of 1 and 2
      differ by ca. 0.3 g cm(-3)(1.654 vs. 1.940 g cm(-3), respectively). Compound 3 is
      isomorphous with 1 and likewise features two chiral interpenetrating nets of
      quartz topology. In 4, chelating bipyridine nitrogen atoms and four carboxylate
      oxygen atoms from a total of five adjacent dcbp ligands provide distorted
      octahedral geometry around Mn(II). The carboxylate groups bridge adjacent Mn(II)
      centres to produce bis-carboxylato chains which cross-link and generate a 3D
      network that is perforated with channels. The channels are occupied with
      disordered DEF molecules. The network topology in 4 is quite different to 1-3 and
      has a (4.6(2))(4(2).6)(4(3).6(6).8(6)) Schlafli notation. Magnetic susceptibility
      studies performed on 1, 2, [[Mn(dcbp)].1/2DMF] 5 (DMF = dimethylformamide) and
      [[Mn(dcbp)].2H(2)O] 6 reveal very weak antiferromagnetic coupling between the
      metal centres in each case.

PMID- 15510261
TI  - The molecular structure of the tris(2-mercapto-1-tolylimidazolyl)hydroborato
      zinc(2-mercapto-1-tolylimidazole) complex, [[Tm(p-Tol)]Zn(mim(p-Tol))][ClO4]:
      intermolecular N-H...OClO3versus intramolecular N-H...S hydrogen bonding
      interactions of the mercaptoimidazole ligand.
AB  - The molecular structure of the tris(2-mercapto-1-tolylimidazolyl)hydroborato
      complex [[Tm(p-Tol)]Zn(mim(p-Tol))][ClO(4)].3MeCN has been determined by X-ray
      diffraction, thereby demonstrating that the mim(p-Tol) ligand exhibits a N-H...O
      hydrogen bond with the [ClO(4)](-) counterion, [[Tm(p-Tol)]Zn(mim(p
      Tol))...(OClO(3))], rather than hydrogen bond with a sulfur of the [Tm(p-Tol)]
      ligand. DFT calculations on a series of related complexes, namely
      [[Tm(Me)]Zn(mim(Me))](+), [[Tm(Me)]Zn(mim(Me))]...(OClO(3))],
      [[Tm(Me)]Zn(mim(Me))]...[O(H)Me]](+), and [[Tm(Me)]Zn(mim(Me))]...(NCMe)](+)
      demonstrate that an intramolecular N-H...S hydrogen bond within
      [[Tm(Me)]Zn(mim(Me))](+) is also less favored than the corresponding hydrogen
      bonding interactions with MeCN, MeOH, and [ClO(4)](-). The inability of the
      sulfur atoms of [Tm(R)] ligand to act as an effective hydrogen bond acceptor is
      in marked contrast to the ability of sulfur atoms in thiolate ligands to
      participate in the formation of N-H...S hydrogen bonds, an observation that
      reflects the "thione"versus"thiolate" nature of the [Tm(R)] ligand.

PMID- 15510262
TI  - Structures and anion-binding properties of M4L6 tetrahedral cage complexes with
      large central cavities.
AB  - Reaction of the bis-bidentate bridging ligand L(3), in which two bidentate
      chelating 3(2-pyridyl)pyrazole units are separated by a 3,3'-biphenyl spacer,
      with Co(II) salts affords tetranuclear cage complexes of composition
      [Co(4)(L(3))(6)]X(8)(X =[BF(4)](-), [ClO(4)](-), [PF(6)](-) or I(-)) in which
      four 6-coordinate Co(II) ions in an approximately tetrahedral array are connected
      by six bis-bidentate bridging ligands, one spanning each of the six edges of the
      Co(4) tetrahedron. In every case, X-ray crystallography reveals that the 'apical'
      Co(II) ion has a fac tris-chelate geometry, whereas the other three Co(II) ions
      have mer tris-chelate geometries, resulting in (non-crystallographic)C(3)
      symmetry for the cages; that this structure is retained in solution is confirmed
      by (1)H NMR spectroscopy of the paramagnetic cages. In every case one of the
      anions is located inside the central cavity of the cage, with the remaining seven
      outside. We found no clear evidence for an anion-based templating effect. The
      cage superstructure is sufficiently large to leave gaps in the centres of the
      faces through which the internal and external anions can exchange. Variable
      temperature (19)F NMR spectroscopy was used to investigate the dynamic behaviour
      of the cages with X =[BF(4)](-) and [PF(6)](-) in MeCN solution: in both cases
      two separate signals, corresponding to external and internal anions, are clear at
      233 K which have coalesced to a single signal at room temperature. Analysis of
      the linewidth of the minor signal (for the internal anion) at various
      temperatures below coalescence gave an activation energy for anion exchange of
      ca. 50 kJ mol(-1) in each case, a figure which suggests that anion exchange can
      occur via a conformational rearrangement of the cage superstructure in solution
      rather than opening of the cavity by cleavage of metal-ligand bonds.

PMID- 15510263
TI  - Effects of diphosphine structure on aurophilicity and luminescence in Au(I)
      complexes.
AB  - The effects of diphosphine flexibility and bite angle on the structures and
      luminescence properties of Au(I) complexes have been investigated. A range of
      diphosphines based on heteroaromatic backbones [bis(2
      diphenylphosphino)phenylether (dpephos), 9,9-dimethyl-4,5
      bis(diphenylphosphino)xanthene (xantphos), and 4,6
      bis(diphenylphosphino)dibenzofuran (dbfphos)] has been used to prepare mono- and
      digold derivatives. A clear relationship between the presence of aurophilic
      contacts and the emission properties of dinuclear complexes has been observed,
      with one of the complexes studied, [Au(2)Cl(2)(micro-xantphos)], exhibiting
      luminescence thermochromism.

PMID- 15510264
TI  - Synthesis and coordination properties of new macrocyclic ligands: equilibrium
      studies and crystal structures.
AB  - The synthesis and characterization of two new macrocyclic ligands, the bis
      macrocyclic compound 2,6-bis(1,4,13-triaza-7,10-dioxacyclopentadec-1
      ylmethyl)phenol (L) and 38-methoxy-1,4,13,16,19,28-hexaaza-7,10,22,25
      tetraoxatricyclo[14.14.7.1(32,36)]octatriconta-32,34,Delta(36,38)-triene (L1) are
      reported. Equilibrium studies of basicity and coordination properties toward
      metal ions such as Cu(II), Zn(II), Cd(II) and Pb(II) were performed for ligand by
      potentiometric measurements in aqueous solution (298.1 +/- 0.1 K, I= 0.15 mol dm(
      3)). L behaves as a hexaprotic base (logK(1)= 10.93, logK(2)= 9.70, logK(3)=
      8.79, logK(4)= 8.05, logK(5)= 6.83, logK(6)= 2.55). All metal ions form stable
      mono- and dinuclear complexes: logK(MLH(-1))= 25.61 for Cu(II), 15.37 for Zn(II),
      12.58 for Cd(II) and 13.79 for Pb(II); logK(M(2)LH(-1))= 31.61 for Cu(II), 23.38
      for Zn(II), 24.49 for Cd(II) and 23.68 for Pb(II). All these dinuclear species
      show a great tendency to add the OH(-) group: the equilibrium constant for the
      addition reaction was found to be logK(M(2)LH(-1)OH)= 4.77 for Cu(II), 5.66 for
      Zn(II), 2.8 for Cd(II) and 3.18 for Pb(II). In the case of Ni(II), kinetic
      inertness prevents the possibility of solution studies. The dinuclear solid
      adducts [Ni(2)H(-1)L(N(3))(3)].EtOH and [Cu(2)H(-1)L(N(3))](ClO(4))(2) were
      characterized by X-ray analysis.

PMID- 15510265
TI  - Molecular precursors to gallium oxide thin films.
AB  - The donor-functionalised alkoxides [Et(2)Ga(OR)](2)(R = CH(2)CH(2)NMe(2)(1),
      CH(CH(2)NMe(2))(2)(2), CH(2)CH(2)OMe (3), CH(CH(3))CH(2)NMe(2)(4),
      C(CH(3))(2)CH(2)OMe (5)) were synthesised by the 1:1 reaction of Et(3)Ga with ROH
      in hexane or dichloromethane at room temperature. Reaction of Et(3)Ga with excess
      ROH in refluxing toluene resulted in the isolation of a 1:1 mixture of
      [Et(2)Ga(OR)](2) and the ethylgallium bisalkoxide [EtGa(OR)(2)](R =
      CH(2)CH(2)NMe(2)(6) or CH(CH(3))CH(2)NMe(2)(7)). X-ray crystallography showed
      that compound 6 is monomeric and this complex represents the first structurally
      characterised monomeric gallium bisalkoxide. Homoleptic gallium trisalkoxides
      [Ga(OR)(3)](2) were prepared by the 1:6 reaction of [Ga(NMe(2))(3)](2) with ROH
      (R = CH(2)CH(2)NMe(2)(8), CH(CH(3))CH(2)NMe(2)(9), C(CH(3))(2)CH(2)OMe (10)). The
      decomposition of compounds 1, 4, 5 and 8 were studied by thermal gravimetric
      analysis. Low pressure CVD of 1 and 5 resulted in the formation of thin films of
      crystalline Ga(2)O(3).

PMID- 15510266
TI  - Syntheses, structures and magnetic properties of Mn(II) dimers [CpMn(micro
      X)]2(Cp = C5H5; X = RNH, R1R2N, C[triple bond]CR).
AB  - Manganocene, Cp(2)Mn, has been employed as a precursor in the synthesis of a
      range of Mn(II) dimers of the type [CpMn(micro-X)](2)[X = 8-NHC(9)H(6)N (1),
      N(Ph)(C(5)H(4)N)(2), N(4-EtC(6)H(4))(C(5)H(4)N)(3) and C[triple bond]CPh (4)] as
      well as the bis-adduct [Cp(2)Mn[HN=C(NMe(2))(2)](2)](5). The solid-state
      structures of 1-5 are reported. Variable-temperature magnetic measurements have
      been used to assess the extent of Mn(micro-X)Mn communication within the dimers
      of 1-4 as a function of the bridging ligands (X).

PMID- 15510267
TI  - Honeycombs, herringbones and brick-walls; three-fold guest-dependent variation in
      copper trimesate complexes bearing sulfimide ligands.
AB  - Reaction of a solution of CuSO(4) and S,S'-diphenylsulfimide, Ph(2)SNH 1, with
      sodium salts of trimesic acid (H(3)tma) in MeOH gives the 2-D coordination
      network [Cu(3)(Ph(2)SNH)(6)(tma)(2)] in which each trimesate is bound to three
      copper centres. Addition of other solvents to the reaction mixture causes a
      change in the shape of the network. By this route, three forms have been prepared
      and characterised by X-ray crystallography. These include the known honeycomb, 2,
      and brick-wall, 3, motifs and a herringbone, 4, arrangement which is novel for
      transition metal-containing trimesate complexes. Key to the supramolecular
      isomerism observed is the ability of 1 to facilitate structural isomerism at
      copper(II) centres. In contrast to 2 in which the copper centres are square
      planar, 4 is analogous to an inter-allogon, with both planar and tetrahedral
      copper centres. Also prepared is a related complex which is composed of discrete
      units of three copper centres. These are further linked into a 2-D network by
      hydrogen bonds.

PMID- 15510268
TI  - Stoichiometry, stability constants and coordination geometry of Eu(III) 5
      sulfosalicylate complex in aqueous system-A TRLIFS study.
AB  - The complex formation between Eu(III) and 5-sulfosalicylate, (HSSA)(2-), has been
      investigated by means of TRLIFS (time resolved laser induced fluorescence
      spectroscopy). The concentration of free ligand in the solution was determined
      from the fluorescence emission of 5-sulfosalicylate by subtracting the dynamic
      quenching effect from the observed quenching of fluorescence emission by means of
      lifetime analysis, and the stoichiometry and the corresponding formation
      constants were obtained. A carboxylate coordinated complex, Eu(HSSA)(+), and also
      a chelate complex, Eu(SSA), were identified, and the formation constants of the
      complex Eu(HSSA)(2+) for the reaction, Eu(3+)+ HSSA(2-)[rightward arrow]
      Eu(HSSA)(+), and the deprotonation constant of the chelating reaction,
      Eu(HSSA)(+)--> Eu(SSA)+ H(+), were calculated at log beta(1,1)= 1.79 and log K'=
      5.78, respectively. TRLIFS using the fluorescence emission from Eu(III) was
      performed in order to determine the number of coordination waters of the complex
      Eu(HSSA)(2+). The quenching of the Eu(III) fluorescence caused by (SSA)(3-)
      disturbed the lifetime analysis of the 'intrinsic lifetime' of Eu(III) in
      Eu(HSSA)(2+), however the problem was successfully solved by the analysis of
      emission intensity and lifetime, and the formulation of the complex was
      determined as [Eu(HSSA)8H(2)O](2+) with the explicit involvement of the
      coordinated waters.

PMID- 15510269
TI  - Ferromagnetic exchange in a dinuclear copper(II) complex mediated by a
      methanolate bridging ligand.
AB  - The copper(II) complex Cu(2)L(OMe)(H(2)O)(3), [middle dot]3H(2)O [H(3)L = 2-(2
      hydroxyphenyl)-1,3-bis[4-(2-hydroxyphenyl)-3-azabut-3-enyl]-1,3-imidazolidine]
      was obtained and recrystallised in methanol to yield crystals of
      [[Cu(2)L(OMe)]](2).2.5MeOH.4H(2)O, 1.2.5MeOH.4H(2)O. Its single X-ray study shows
      that it contains two crystallographically different but chemically equivalent
      dinuclear [Cu(2)L(OMe)] 1 molecules in the asymmetric unit cell. The copper atoms
      of each dinuclear moiety are in distorted square-pyramidal environments, with
      both pyramids sharing an apical phenolate and a basal methanolate oxygen atom.
      Magnetic characterisation of 1.3H(2)O shows a quite strong intramolecular
      ferromagnetic coupling between both metal atoms. Extended Huckel calculations
      reveal that the intradinuclear magnetic interaction seems to be mediated by the
      exogenous methanolate bridging ligand.

PMID- 15510270
TI  - Nickel(III) oxidation of its glycylglycylhistamine complex.
AB  - The doubly-deprotonated Ni(III) complex of Gly(2)Ha (where Ha is histamine)
      undergoes base-assisted oxidative self-decomposition of the peptide. At </=
      p[H(+)] 7.0, a major pathway is a two-electron oxidation at the alpha-carbon of
      the N-terminal glycyl residue. Major products (up to 73%) of this two-electron
      oxidation are glyoxylglycylhistamine and ammonia. Glyoxylglycylhistamine will
      decay to give isocyanatoacetylhistamine and formaldehyde. Two-electron oxidations
      of the second glycyl and histamine residues occur as minor pathways (12% of the
      total possible reaction). Above p[H(+)] 8.5, two Ni(III)-peptide complexes form
      an oxo bridge in the axial positions to give a reactive dimer species. This
      proximity allows the resulting Ni(II)-peptide radical intermediates to undergo
      peptide-peptide cross-linking at the N-terminal glycyl residues. The products
      found below p[H(+)] 7.0 are observed above p[H(+)] 8.5 as well, although in lower
      yields. In contrast to this work, Ni(III)(H(-2)Gly(2)HisGly) undergoes a four
      electron oxidation at the N-terminal glycyl residue. Oxidation at the internal
      glycyl and histidyl residues are not observed. The reactivity of Ni(III)(H(
      2)Gly(2)Ha)(+) is also different than Cu(III)(H(-2)Gly(2)Ha)(+), which undergoes
      a two-electron oxidation at the histamine group with no peptide-peptide cross
      linking in basic solution.

PMID- 15510271
TI  - Monomeric, one- and two-dimensional networks incorporating (2,6-Me2C6H3S)2Pb
      building blocks.
AB  - The amine coordination of lead(II) has been examined through the preparation and
      structural analysis of Lewis base adducts of bis(thiolato)lead(II) complexes.
      Reaction of Pb(OAc)(2) with 2,6-dimethylbenzenethiol affords (2,6
      Me(2)C(6)H(3)S)(2)Pb (6) in high yield. The solubility of 6 in organic solvents
      allows for the preparation of the 1:2 Lewis acid-base adduct [(2,6
      Me(2)C(6)H(3)S)(2)Pb(py)(2)](7), and 1:1 adducts [(2,6
      Me(2)C(6)H(3)S)(2)Pb(micro(2)-bipy)](infinity](8) and [(2,6
      Me(2)C(6)H(3)S)(2)Pb(micro(2)-pyr)](infinity)(9)(where py = pyridine, bipy = 4,4'
      bipyridyl and pyr = pyrazine) from reaction with an excess of the appropriate
      amine. In contrast to 7, reaction of (C(6)H(5)S)(2)Pb (1) with pyridine afforded
      the 2:1 adduct [(C(6)H(5)S)(4)Pb(2)(py)](infinity)(10). Compounds were
      characterized via elemental analysis, FT-IR, solution (1)H and (13)C[(1)H](6) NMR
      spectroscopy, and X-ray crystallography (7-10). The structures of 7-9 show the
      thiolate groups occupying two equatorial positions and two amine nitrogen atoms
      occupying axial coordination sites, yielding distorted see-saw coordination
      geometries, or distorted trigonal bipyramids if an equatorial lone pair on lead
      is considered. The absence of intermolecular contacts in 7 and 8 result in
      monomeric and one-dimensional polymeric structures, respectively. Weak Pb...S
      intermolecular contacts in 9 result in the formation of a two-dimensional
      macrostructure. In contrast, the structure of , shows extensive intermolecular
      Pb...S interactions, resulting in five- and six-coordinate bonding environments
      for lead(II), and a complex polymeric structure in the solid state. This
      demonstrates the ability of the 2,6-dimethylphenylthiolate ligand to limit
      intermolecular lead-sulfur interactions, while allowing the axial coordination of
      amine Lewis base ligands.

PMID- 15510272
TI  - Condensation reactions of monomeric hydroxo palladium complexes with active
      methyl and methylene compounds.
AB  - Heating a suspension of the monomeric hydroxo palladium complex of the type [Pd(N
      N)(C(6)F(5))(OH)](N-N = bipy, Me(2)bipy, phen or tmeda) in methylketone (acetone
      or methylisobutylketone) under reflux affords the corresponding ketonyl palladium
      complex [Pd(N-N)(C(6)F(5))(CH(2)COR)]. On the other hand, the reaction of the
      hydroxo palladium complexes [Pd(N-N)(C(6)F(5))(OH)](N-N = bipy, phen or tmeda)
      with diethylmalonate or malononitrile yields the C-bound enolate palladium
      complexes [Pd(N-N)(CHX(2))(C(6)F(5))](X = CO(2)Et or CN), and the reaction of
      [Pd(N-N)(C(6)F(5))(OH)](N-N = bipy or phen) with nitromethane gives the
      nitromethyl palladium complexes [Pd(N-N)(CH(2)NO(2))(C(6)F(5))].
      [Pd(tmeda)(C(6)F(5))(OH)] catalyses the cyclotrimerization of malononitrile. The
      crystal structures of [Pd(bipy)(C(6)F(5))(CH(2)COMe)].1/2Me(2)CO,
      [Pd(tmeda)(C(6)F(5))[CH(CO(2)Et)(2)]], [Pd(tmeda)(C(6)F(5))[CH(CN)(2)]] and
      [Pd(tmeda)(C(6)F(5))(CH(2)NO(2))].1/2CH(2)Cl(2) have been established by X-ray
      diffraction.

PMID- 15510273
TI  - Synthesis, structure and reactivity of palladium(II) complexes of chiral N
      heterocyclic carbene-imine and -amine hybrid ligands.
AB  - The synthesis and structures of chiral N-heterocyclic carbene (NHC)-N-donor
      complexes of silver(I) and palladium(II) are reported. The X-ray structure of an
      NHC-imine silver(I) complex [((nPr)CN(CHPh))AgBr](2) exhibits an Ag(2)Br(2) dimer
      motif where the imine group is not coordinated to the silver atom. Reaction
      between 2 and [PdCl(2)(MeCN)(2)] gives the palladium(II) complex [(kappa(2)
      (nPr)CN(CHPh))PdCl(2)](3) that contains a chelating NHC-imine ligand as shown by
      single-crystal X-ray diffraction. Slow hydrolysis of related complexes [(kappa(2)
      (nPr)CN(CHPh))PdCl(2)](3) and [(kappa(2)-((Ph)(2)CH)CN(CHPh))PdCl(2)](4) using
      triethylammonium chloride and water lead to the precipitation of single crystals
      of insoluble NHC-amino palladium(II) complexes [(kappa(2)
      (nPr)CN(H(2)))PdCl(2)](6) and [(kappa(2)-((Ph)(2)CH)CN(H(2)))PdCl(2)](7),
      respectively. In the solid state, complexes 6 and 7 both exhibit intermolecular
      hydrogen bonding between chlorine and an amino-hydrogen atom resulting in an
      infinite chain structure. Substitution of an amino hydrogen for an ethyl group
      gives the soluble complex [(kappa(2)-(iPr)CN((H)Et))PdCl(2)](12). Reaction
      between two equivalents of 2 and [PdCl(2)(MeCN)(2)] gives the di-NHC complex
      [(kappa(1)-(nPr)CN(CHPh))(2)PdCl(2)](5) that does not contain a coordinated imine
      as shown by single crystal X-ray diffraction. Conproportionation between 5 and an
      equivalent of [PdCl(2)(MeCN)(2)] to does not occur at temperatures up to 100
      degrees C in CD(3)CN.

PMID- 15510275
TI  - Synthesis and structures of aluminium monohydride and chalcogenides bearing a
      bidentate [N,O] ligand.
AB  - The aluminium monohydride (3-tBu-5-Me-2-(O)C(6)H(2)CH(2)-N-2,6
      iPr(2)C(6)H(3))AlH(NMe(3))(2) was prepared by treatment of the bidentate
      salicylaldimine [3-tBu-5-Me-2-(OH)C(6)H(2)CH=N-2,6-iPr(2)C(6)H(3)](1) with a
      small excess of AlH(3).NMe(3) in high yield. Compound 2 reacted with sulfur and
      selenium respectively to afford the dimeric aluminium chalcogenide [(3-tBu-5-Me-2
      (O)C(6)H(2)CH(2)-NH-2,6-iPr(2)C(6)H(3))Al(micro-E)](2)[E = S (3), E = Se (4)].
      During the formation of 2 hydrogen migration from the aluminium centre to the
      ligand backbone occurred. A possible reaction mechanism for 3 and 4 is discussed
      and the molecular structures of compounds 2-4 were determined by X-ray structural
      analyses.

PMID- 15510274
TI  - Inside or outside a ligand cleft? Synthetic, structural, and kinetic inertness
      studies of zinc, cadmium, and mercury complexes of cross-bridged cyclam and
      cyclen.
AB  - Ethylene cross-bridging of the popular tetraazamacrocyclic ligand cyclam has led
      to metal complexes with enhanced kinetic inertness. The synthesis and spectral
      characterization of zinc(II), cadmium(II), and mercury(II) complexes of cross
      bridged cyclam (L1) as well as cross-bridged cyclen (L2) are reported along with
      the details of our synthetic route to L2. X-ray structural studies revealed that
      all Zn(II) and Cd(II) cations are fully kappa(4)N-coordinated inside the
      respective ligand's molecular cleft with L1 providing the better fit for Zn(II).
      While Hg(II) is similarly coordinated to L2, it has been found to complex L1
      outside the ligand cleft in a novel exo-kappa(2)N-mode. Solution NMR data of the
      kappa(4)N complexes are consistent with the presence of only a single cis-folded
      isomer in each case. Ligand (1)H and (13)C coupling to both (111,113)Cd and
      (199)Hg in their complexes can be clearly discerned. The relative kinetic
      inertness of representative cross-bridged complexes in acidic aqueous solution
      has been assessed and found to be in the following order: Zn(II) > Cd(II)[dbl
      greater-than] Hg(II). The data also reaffirm that cross-bridged cyclam ligand L1
      forms a substantially more inert complex with zinc(II) than either the smaller
      cyclen analogue L2 or the unbridged 1,4,8,11-tetramethyl-cyclam L3.

PMID- 15510276
TI  - Monocarbaborane anion chemistry. [COOH], [CH2OH] and [CHO] units as functional
      groups on ten-vertex monocarbaborane anionic compounds.
AB  - B(10)H(14) reacts with para-C(6)H(4)(CHO)(COOH) in aqueous KOH solution to give
      the [nido-6-CB(9)H(11)-6-(C(6)H(4)-para-COOH)](-) anion 1, which undergoes cage
      closure with iodine in alkaline solution to give the [closo-2-CB(9)H(9)-2
      (C(6)H(4)-para-COOH)](-) anion 2. Upon heating, anion 2 rearranges to form the
      [closo-1-CB(9)H(9)-1-(C(6)H(4)-para-COOH)](-) anion 3. Similarly, B(10)H(14) with
      glyoxylic acid OHCCOOH in aqueous KOH gives the [arachno-6-CB(9)H(13)-6-(COOH)](
      ) anion 4, which undergoes cage closure with iodine in alkaline solution to give
      the [closo-2-CB(9)H(9)-2-(COOH)](-) anion 5. Upon heating, anion 5 rearranges to
      give the [closo-1-CB(9)H(9)-1-(COOH)](-) anion 6. Reduction of the [COOH] anions
      3 and 6 with diisobutylaluminium hydride gives the [CH(2)OH] hydroxy anions
      [closo-1-CB(9)H(9)-1-(C(6)H(4)-para-CH(2)OH)](-) and [closo-1-CB(9)H(9)-1
      (CH(2)OH)](-) 8 respectively. The [closo-1-CB(9)H(9)-1-(C(6)H(4)-para-CH(2)OH)](
      ) anion 7 can also be made via isomerisation of the [closo-2-CB(9)H(9)-2
      (C(6)H(4)-para-CH(2)OH)](-) anion 9, in turn obtained from the [nido-6-CB(9)H(11)
      6-(C(6)H(4)-para-CH(2)OH)](-) anion 10, which is obtained from the reaction of
      B(10)H(14) with terephthaldicarboxaldehyde, C(6)H(4)-para-(CHO)(2), in aqueous
      KOH solution. Oxidation of the hydroxy anions 7 and 8 with pyridinium dichromate
      gives the aldehydic [closo-1-CB(9)H(9)-1-(C(6)H(4)-para-CHO)](-) anion 11 and the
      aldehydic [closo-1-CB(9)H(9)-1-(CHO)](-) anion 12 respectively, characterised as
      their 2,4-dinitrophenylhydrazone derivatives, the [closo-1-CB(9)H(9)-1-C(6)H(4)
      para-CH=N-NHC(6)H(3)(NO(2))(2)](-) anion 13 and the [closo-1-CB(9)H(9)-1-CH=N
      NHC(6)H(3)(NO(2))(2)](-) anion respectively.

PMID- 15510277
TI  - Energetics of the Preyssler anion's molecular orbitals: quantifying the effect of
      the encapsulated-cation's charge.
AB  - The ground state electronic properties of metal-exchanged Preyssler
      heteropolyoxoanions [M(n+)P(5)W(30)O(110)](n-15), in which the encapsulated M(n+)
      ions are the spherical, diamagnetic ions Na(+), Ca(2+), Sr(2+), Y(3+), La(3+) and
      Th(4+), are studied using a combination of electrochemical, optical, and NMR
      experiments. We have designed experiments that focus on the influence of the
      charge (n) of the encapsulated cations, which themselves have no redox response,
      and its effect upon the W-O framework MOs. As n increases, the cluster anions
      accept electrons into their LUMOs with increasing ease, and their lowest-energy
      LMCT bands reveal a corresponding blue shift, which is indicative of an increase
      of the LUMO-HOMO energy splitting with increasing n. (183)W NMR spectra are used
      to identify the atomic origin of the LUMO states, which are shown to be composed
      primarily of orbitals from the ring of 5 W atoms near M(n+). The cation charge
      correlates directly and linearly with the half-wave potentials of the first redox
      couples, the LMCT band energies, and the W chemical shifts. We have combined this
      suite of experimental results to construct an energy level diagram of the
      frontier MOs for the Preyssler cluster anions. In so doing, we provide a
      fundamental perspective that is not otherwise available on the cation's role with
      specific regard to the electronic behavior of the W-O orbitals. These results are
      expected to provide benchmarking information as theorists begin to study these
      large POM systems.

PMID- 15510278
TI  - The structural characteristics of organozinc complexes incorporating N,N'
      bidentate ligands.
AB  - Dimethylzinc reacts with an excess of N-2-pyridylaniline 6 to give the homoleptic
      species, Zn[PhN(2-C(5)H(4)N)](2) 8. Single crystal X-ray diffraction reveals a
      solid-state dimer based on an 8-membered (NCNZn)(2) core motif. Zn[CyN(2
      C(5)H(4)N)]Me (Cy =c-C(6)H(11)) 10, prepared by the combination of ZnMe(2) with
      the corresponding cyclohexyl-substituted pyridylamine, is also dimeric in the
      solid state but reveals a central (ZnN)(2) metallacycle. Employment of (p
      Tol)NH(2-C(5)H(4)N)(p-Tol = 4-MeC(6)H(4)) 11 yielded the tris(zinc) adduct
      Zn(3)[(p-Tol)N(2-C(5)H(4)N)](4)Me(2) 12, which incorporates a central chiral
      molecule of 'Zn[(p-Tol)N(2-C(5)H(4)N)](2)' 12a, that bridges two 'Zn[(p-Tol)N(2
      C(5)H(4)N)]Me' 12b units. A similar trimetallic structure is noted when the
      pyridylaniline substrate 11 is replaced with the bicyclic guanidine 1,3,4,6,7,8
      hexahydro-2H-pyrimido[1,2-a]pyrimidine (hppH), affording Zn(3)(hpp)(4)Me(2) 13.
      Spectroscopic studies point to retention of the solid-state structure of in
      hydrocarbon solution. Reaction of 13 with dimesityl borinic acid, Mes(2)BOH (Mes
      = mesityl), affords Zn(3)(hpp)(4)(OBMes(2))(2) 14 in which the trimetallic core
      is retained. This reactivity is in contrast to the closely related reaction of
      dimeric Zn[Me(2)NC[N(i)Pr](2)]Me 15 with Mes(2)BOH, which yielded
      Zn[Me(2)NC[N(i)Pr](2)][OBMes(2)].Me(2)NC[N(i)Pr][NH(i)Pr] 16 as a result of
      protonation at the guanidine ligand in addition to the Zn-Me bond.

PMID- 15510279
TI  - Syntheses and chemistry of hypervalent cyclo-R4Sb4, cyclo-(RSbE)n[R = 2
      (Me2NCH2)C6H4, E = O, S] and precursors.
AB  - The cyclostibane R(4)Sb(4)(1)(R = 2-(Me(2)NCH(2))C(6)H(4)) was synthesized by
      reduction of RSbCl(2) with Mg in THF or with Na in liquid NH(3). The reaction of
      1 with [W(CO)(5)(THF)] gives the stibinidene complex RSb[W(CO)(5)](2)(2).
      RSbCl(2) and (RSbCl)(2)E [E = O (6), E = S (8)] react with KOH or Na(2)S in
      toluene/water to give the heterocycles (RSbE)(n)[E = O, n= 3 (3); E = S, n= 2
      (4)]. The chalcogeno-bridged compounds of the type (RSbCl)(2)E [E = O (6), E = S
      (8)] were synthesized by reaction of RSbCl(2) with KOH or Na(2)S in
      toluene/water, but also by reaction of RSbCl(2) with the heterocycles (RSbE)(n).
      The compounds (RSbI)(2)O (7) and (RSbBr)(2)S (9) were prepared via halogen
      exchange reactions between (RSbCl)(2)E and NaI (E = O) or KBr (E = S) or by
      reactions between RSbI(2) and KOH or RSbBr(2) and Na(2)S. The reaction of cyclo
      (RSbS)(2) with W(CO)(5)(THF) in THF results in trapping of the cis isomer in
      cyclo-(RSbS)(2)[W(CO)(5)](5). The solution behaviour of the compounds was
      investigated by (1)H and (13)C NMR spectroscopy. The molecular structures of
      compounds 1-7 and 9 were determined by single-crystal X-ray diffraction.

PMID- 15510280
TI  - Complexes of a novel multinucleating poly-beta-diketonate ligand.
AB  - The synthesis of the new polynucleating ligand 1,3-bis-(3-oxo-3-(2-hydroxyphenyl)
      propionyl)-benzene (H4L) is reported along with the preparation, structure and
      properties of its dinuclear complexes [Cu(2)(H(2)L)(2)(py)(2)](1),
      [Ni(2)(H(2)L)(2)(py)(4)](2), [Mn(2)(H(2)L)(2)(dmf)(4)](3),
      [Co(2)(H(2)L)(2)(dmf)(4)](4) and [Co(2)(H(2)L)(2)(MeOH)(4)](5), respectively. In
      complexes 1 to 5, the polydentate ligand is in its bis-deprotonated form,
      chelating the metals through its [small beta]-diketonate moieties. Magnetic
      measurements show that the metals within these molecules are maintained almost
      mutually independent.

PMID- 15510281
TI  - Preparation of mononuclear and dinuclear Rh hydrotris(pyrazolyl)borato complexes
      containing arenethiolato ligands and conversion of the mononuclear complexes into
      dinuclear Rh-Rh and Rh-Ir complexes with bridging arenethiolato ligands.
AB  - Reactions of [Tp*Rh(coe)(MeCN)](; Tp*= HB(3,5-dimethylpyrazol-1-yl)(3); coe =
      cyclooctene) with one equiv. of the organic disulfides, PhSSPh, TolSSTol (Tol = 4
      MeC(6)H(4)), PySSPy (Py = 2-pyridyl), and tetraethylthiuram disulfide in THF at
      room temperature afforded the mononuclear Rh(III) complexes
      [Tp*Rh(SPh)(2)(MeCN)](3a), [Tp*Rh(STol)(2)(MeCN)](3b), [Tp*Rh(eta(2)-SPy)(eta(1)
      SPy)](6), and [Tp*Rh(eta(2)-S(2)CNEt(2))(eta(1)-S(2)CNEt(2))](7), respectively,
      via the oxidative addition of the organic disulfides to the Rh(I) center in 1.
      For the Tp analogue [TpRh(coe)(MeCN)](2, Tp = HB(pyrazol-1-yl)(3)), the reaction
      with TolSSTol proceeded similarly to give the bis(thiolato) complex
      [TpRh(STol)(2)(MeCN)](4) as a major product but the dinuclear complex
      [[TpRh(STol)](2)(micro-STol)(2)](5) was also obtained in low yield. Complex 3 was
      treated further with the Rh(III) or Ir(III) complexes [(Cp*MCl)(2)(micro
      Cl)(2)](Cp*=eta(5)-C(5)Me(5)) in THF at room temperature, yielding the thiolato
      bridged dinuclear complexes [Tp*RhCl(micro-SPh)(2)MCp*Cl](8a: M = Rh, 8b: M =
      Ir). Dirhodium complex [TpRhCl(micro-STol)(2)RhCp*Cl](9) was obtained similarly
      from 4 and [(Cp*RhCl)(2)(micro-Cl)(2)]. Anion metathesis of 8a proceeds only at
      the Rh atom with the Cp* ligand to yield [Tp*RhCl(micro
      SPh)(2)RhCp*(MeCN)][PF(6)](10), when treated with excess KPF(6) in CH(2)Cl(2)
      MeCN. The X-ray analyses have been undertaken to determine the detailed
      structures of 3b, 4, 5, 6, 7, 8a, 9, and 10.

PMID- 15510282
TI  - Reactions of tris(oxalato)cobaltate(III) with two-electron reductants.
AB  - The tris(oxalato)cobaltate(III) complex [Co(C(2)O(4))(3)](3-),
      E(o)(Co)(III/II)=+0.57 V) is readily reduced by the 2e(-) reagents, Sn(II) and
      Ge(II), in contrast to (NH(3))(5)CoCl(2+) and (NH(3))(5)CoBr(2+), which are
      unreactive toward these donors. Rates for the oxalato oxidant are only 10(-3)-10(
      2) as great as those for vitamin B(12a)(aquacob(III)alamin, E(o)+0.35 V at pH 1),
      in accord with the suggestion that reductions of corrin-bound cobalt(III) by
      Sn(II) and Ge(II) occur predominantly through an additional path involving Co(i).
      Reductions of the oxalato complex by 2e(-) donors are taken to proceed by initial
      formation of odd-electron intermediates (e.g., Sn(III) and Ge(III)) which react
      rapidly with Co(III). Such a two-step sequence is in keeping with the observed
      behavior of the rare reductant, Ti(II), which is found to be oxidized by
      [Co(C(2)O(4))(3)](3-) more slowly than (independently prepared) Ti(III) under
      comparable conditions.

PMID- 15510283
TI  - Extraction and coordination studies of the unexplored bifunctional ligand
      carbamoyl methyl sulfoxide (CMSO) with uranium(VI) and cerium(III) nitrates.
      Synthesis and structures of [UO2(NO3)2(PhSOCH2CON(i)Bu2)] and
      [Ce(NO3)3(PhSOCH2CONBu2)2].
AB  - The bifunctional carbamoyl methyl sulfoxide ligands, PhCH(2)SOCH(2)CONHPh (L1),
      PhCH(2)SOCH(2)CONHCH(2)Ph (L2), PhSOCH(2)CON(i)Pr(2)(L3), PhSOCH(2)CONBu(2)(L4),
      PhSOCH(2)CON(i)Bu(2)(L5) and PhSOCH(2)CON(C(8)H(17))(2)(L6) have been synthesized
      and characterized by spectroscopic methods. The selected coordination chemistry
      of L1, L3, and L5with [UO(2)(NO(3))(2)] and [Ce(NO(3))(3)] has been evaluated.
      The structures of the compounds [UO(2)(NO(3))(2)(PhSOCH(2)CON(i)Bu(2))](10) and
      [Ce(NO(3))(3)(PhSOCH(2)CONBu(2))(2)](12) have been determined by single crystal X
      ray diffraction methods. Preliminary extraction studies of ligand L6 with U(VI),
      Pu(IV) and Am(III) in tracer level showed an appreciable extraction for U(VI) and
      Pu(IV) in up to 10 M HNO(3) but not for Am(III). Thermal studies on compounds 8
      and 10 in air revealed that the ligands can be destroyed completely on
      incineration. The electron spray mass spectra of compounds 8 and 10 in acetone
      show that extensive ligand distribution reactions occur in solution to give a
      mixture of products with ligand to metal ratios of 1: 1 and 2 :1. However, 10
      retains its solid state structure in CH(2)Cl(2).

PMID- 15510284
TI  - Synthesis and proposed crystal structure of a disordered cadmium arsenate apatite
      Cd5(AsO4)3Cl(1-2x-y)O(x)[symbol: see text](x)OH(y).
AB  - During a study into the synthesis of minerals composed of mining wastes aimed at
      improving their immobilisation, a cadmium arsenate apatite has been prepared by
      hydrothermal methods. The structure of this apatite was analysed by single
      crystal X-ray diffraction, and was found to consist of a standard apatite
      framework based on Cd(5)(AsO(4))(3)X, where X represents an anion resident on the
      (0,0,0.25) site. The framework is hexagonal with the space group P6(3)/m(no 176),
      a= 9.9709(8), c= 6.4916(4)[Angstrom]. The X ion site is predominantly occupied by
      Cl(-) ions; however due to significant shortening of the c axis exhibited by all
      cadmium containing apatite phases, a pure chlorapatite is not possible without a
      significant cation deficiency. No evidence of the necessary deficiency was found
      in the crystal structure. For larger bromo- and iodo-apatites significant
      modulations along the c-axis are required to accommodate the halide. This paper
      examines a number of compensation mechanisms and proposes that a minor disorder
      of chloride, oxide and hydroxide located on the X ion site provides the required
      charge compensation mechanism. This is contrary to previous complex modulations
      proposed in the literature. The proposed chemical formula is Cd(5)(AsO(4))(3)Cl(1
      2x-y)O(x)[symbol:see text](x)OH(y) where [symbol: see text] represents a vacancy.

PMID- 15510285
TI  - A combined parahydrogen and theoretical study of H2 activation by 16-electron d8
      ruthenium(0) complexes and their subsequent catalytic behaviour.
AB  - The photochemical reaction of Ru(CO)(3)(L)(2), where L = PPh(3), PMe(3), PCy(3)
      and P(p-tolyl)(3) with parahydrogen (p-H(2)) has been studied by in-situ NMR
      spectroscopy and shown to result in two competing processes. The first of these
      involves loss of CO and results in the formation of the cis-cis-trans-L isomer of
      Ru(CO)(2)(L)(2)(H)(2), while in the second, a single photon induces loss of both
      CO and L and leads to the formation of cis-cis-cis Ru(CO)(2)(L)(2)(H)(2) and
      Ru(CO)(2)(L)(solvent)(H)(2) where solvent = toluene, THF and pyridine (py). In
      the case of L = PPh(3), cis-cis-trans-L Ru(CO)(2)(L)(2)(H)(2) is shown to be an
      effective hydrogenation catalyst with rate limiting phosphine dissociation
      proceeding at a rate of 2.2 s(-1) in pyridine at 355 K. Theoretical calculations
      and experimental observations show that H(2) addition to the Ru(CO)(2)(L)(2)
      proceeds to form cis-cis-trans-L Ru(CO)(2)(L)(2)(H)(2) as the major product via
      addition over the pi-accepting OC-Ru-CO axis.

PMID- 15510286
TI  - Cp*Rh complexes with pyridyloxazolines: synthesis, fluxionality and applications
      as asymmetric catalysts for Diels-Alder reactions.
AB  - Half-sandwich complexes [RhCl(pymox)Cp*][SbF(6)](1-7)(pymox = pyridyloxazoline)
      have been synthesised as single diastereomers. Treatment of these with AgSbF(6)
      generates dications [Rh(OH(2))(pymox)Cp*](2+) which are fluxional at room
      temperature and which are enantioselective catalysts for the Diels-Alder reaction
      of methacrolein and cyclopentadiene. Treatment of the dication [Rh(OH(2))((i)Pr
      pymox)Cp*](2+) with [X](-) gives [RhX((i)Pr-pymox)Cp*][SbF(6)](X = Br, I) as
      single diastereomers whilst reaction with 4-Mepy (4-methylpyridine) gives [Rh(4
      Mepy)((i)Pr-pymox)Cp*][SbF(6)] as a mixture of diastereomers. Two complexes,
      [RhCl((i)Pr-pymox)Cp*][SbF(6)](3) and [RhCl(Bz-pymox)Cp*][SbF(6)](6) have been
      characterised by X-ray crystallography.

PMID- 15510287
TI  - Water-soluble ruthenium(II) catalysts [RuCl2(eta6-arene)[P(CH2OH)3]] for
      isomerization of allylic alcohols and alkyne hydration.
AB  - The novel water-soluble ruthenium(II) complexes [RuCl(2)(eta(6)
      arene)[P(CH(2)OH)(3)]]2a-c and [RuCl(eta(6)-arene)[P(CH(2)OH)(3)](2)][Cl]3a-c
      have been prepared in high yields by reaction of dimers [[Ru(eta(6)-arene)(micro
      Cl)Cl](2)](arene = C(6)H(6)1a, p-cymene 1b, C(6)Me(6)1c) with two or four
      equivalents of P(CH(2)OH)(3), respectively. Complexes 2/3a-c are active catalysts
      in the redox isomerization of several allylic alcohols into the corresponding
      saturated carbonyl compounds under water/n-heptane biphasic conditions. Among
      them, the neutral derivatives [RuCl(2)(eta(6)-C(6)H(6))[P(CH(2)OH)(3)]]2a and
      [RuCl(2)(eta(6)-p-cymene)[P(CH(2)OH)(3)]]2b show the highest activities (TOF
      values up to 600 h(-1); TON values up to 782). Complexes 2/3a-c also catalyze the
      hydration of terminal alkynes.

PMID- 15510288
TI  - Photolytic and thermal properties of a new series of intramolecular bridged alkyl
      cobaloxime complexes.
AB  - The photolytic kinetic properties of a new series of intramolecular bridged alkyl
      cobaloxime complexes Br(O-C(3)H(6)-(dmgH))(dmgH))Co(III)(2), [H(2)O(O-C(3)H(6)
      (dmg))(dmgH(2))]Co(III)[ClO(4)(3), ]Py(O-C(3)H(6)
      (dmg))(dmgH(2))[Co(III)]ClO(4)(4), [Bzm(O-C(3)H(6)
      (dmg))(dmgH(2))]Co(III)[ClO(4)(5) and ]Im(O-C(3)H(6)
      (dmg))(dmgH(2))[Co(III)]ClO(4)(6) and their precursor aqua-(3
      bromopropyl)cobaloximes (1) were investigated by UV-Vis spectroscopy. The
      products of photolytic solutions were characterized by both ESI-MS and (1)H-NMR
      techniques. Our results revealed a carbon-center radical that is produced from Co
      C bond cleavage under photolysis might be linked to the equatorial ligand and
      thus retained in the proximity of Co(II)-complex. The thermo-gravimetric analysis
      of complex 2 gives the same conclusion.

PMID- 15510289
TI  - Phenolate and phenoxyl radical complexes of Co(II) and Co(III).
AB  - The new phenol-imidazole pro-ligands (R)LH react with Co(BF(4))(2).6H(2)O in the
      presence of Et(3)N to form the corresponding [Co(II)((R)L)(2)] compound (R = Ph
      (1), PhOMe (2), or Bz (3)). Also, (Bz)LH, reacts with Co(ii) in the presence of
      Et(3)N and H(2)O(2) to form [Co(III)((Bz)L)(3)](4). The structures of 1.2.5MeCN,
      2.2DMF, 3.4MeOH, and 4.4DMF have been determined by X-ray crystallography. 1, 2,
      and 3 each involve Co(II) bound to two N,O-bidentate ligands with a distorted
      tetrahedral coordination sphere; 4 involves Co(III) bound to three N,O-bidentate
      ligands in a mer-N(3)O(3) distorted octahedral geometry. [Co(II)((R)L)(2)](R = Ph
      or PhOMe) undergo two, one-electron, oxidations. The products of the first
      oxidation, [1](+) and [2](+), have been synthesised by the chemical oxidation of
      1 and 2, respectively; these cations, formulated as [Co(II)((R)L*)((R)L)(2)](+),
      comprise one phenoxyl radical and one phenolate ligand bound to Co(II) and are
      the first phenoxyl radical ligand complexes of tetra-coordinated Co(II). 4
      undergoes two, one-electron, ligand-based oxidations, the first of which produces
      [4](+), [Co(III)((Bz)L*)((Bz)L)(2)](+). Unlike [1](+) and [2](+), product of the
      one-electron oxidation of [Co(II)((Bz)L)(2)], [3](+), is unstable and decomposes
      to produce [4](+). These studies have demonstrated that the chemical properties
      of [M(II)((R)L*)((R)L)(2)](+)(M = Co, Cu, Zn) are highly dependent on the nature
      of both the ligand and the metal centre.

PMID- 15510290
TI  - Synthesis, characterization, and stereochemistry of S-bridged Co(III)MCo(III)(M =
      Pd(II), Pt(II)) trinuclear complexes containing two non-bridging thiolato groups:
      building blocks for the construction of chiral heterometallic aggregates.
AB  - The reaction of fac(S)-[Co(aet)(3)](aet = aminoethanethiolate) with [PdCl(4)](2-)
      in a 2:1 ratio in water gave an S-bridged Co(III)Pd(II)Co(III) trinuclear complex
      composed of two mer(S)-[Co(aet)(3)] units, [Pd[Co(aet)(3)](2)](2+)([1](2+)). In
      [1](2+), each of the two mer(S)-[Co(aet)(3)] units is bound to a square-planar
      Pd(II) ion through two of three thiolato groups, leaving two non-bridging
      thiolato groups at the terminal. Of two geometrical forms, syn and anti, possible
      for [Pd[Co(aet)(3)](2)](2+), which arise from the difference in arrangement of
      two terminal non-bridging thiolato groups, [1](2+) afforded only the syn form. A
      similar reaction of fac(S)-[Co(aet)(3)] with [PtCl(4)](2-) or trans
      [PtCl(2)(NH(3))(2)] produced an analogous Co(III)Pt(II)Co(III) trinuclear
      complex, [Pt[Co(aet)(3)](2)](2+)([2](2+)), but both the syn and anti forms were
      formed for [2](2+). Complexes [1](2+) and syn- and anti-[2](2+), which
      exclusively exist as a racemic(DeltaDelta/LambdaLambda) form, were successfully
      optically resolved with use of [Sb(2)(R,R-tartrato)(2)](2-) as the resolving
      agent. The reaction of syn-[2](2+) with [AuCl[S(CH(2)CH(2)OH)(2)]] led to the
      formation of an S-bridged Co(III)(4)Pt(II)(2)Au(I)(2) octanuclear metallacycle,
      [Au(2)[Pt[Co(aet)(3)](2)](2)](6+)([3](6+)), while the corresponding reaction of
      anti-[2](2+) afforded a different product ([[4](3+)](n)) that is assumed to have
      a polymeric structure in [[Au[Pt[Co(aet)(3)](2)]](3+)](n).

PMID- 15510291
TI  - Pseudo-rotation mechanism for fast olefin exchange and substitution processes at
      orthometalated C,N-complexes of platinum(II).
AB  - Bridge splitting in chloroform of the orthometalated chloro-bridged complex
      [Pt(micro-Cl)(2-Me(2)NCH(2)C(6)H(4))](2)(1), with ethene, cyclooctene, allyl
      alcohol and phosphine according to 1+ 2L --> 2[PtCl(2-Me(2)NCH(2)C(6)H(4))(L)],
      where L = C(2)H(4)(3a), C(8)H(14), (3b), CH(2)CHCH(2)OH (3c), and PPh(3)(4a and
      4b) gives monomeric species with L coordinated trans or cis to aryl. With olefins
      the thermodynamically stable isomer with L coordinated cis to aryl is formed
      directly without an observable intermediate. With phosphine and pyridine, the
      kinetically controlled trans-product isomerizes slowly to the more stable cis
      isomer. Bridge splitting by olefins is slow and first-order in 1 and L, with
      largely negative DeltaS(++). Substitution of ethene cis to aryl by cyclooctene
      and allyl alcohol to form 3b and 3c, and substitution of cot from 3b by allyl
      alcohol to form 3c are first order in olefin and complex, ca. six orders of
      magnitude faster than bridge cleavage due to a large decrease in DeltaH(++), and
      with largely negative DeltaS(++). Cyclooctene exchange at 3b is first-order with
      respect to free cyclooctene and platinum complex. All experimental data for
      olefin substitution and exchange are compatible with a concerted
      substitution/isomerization process via a turnstile twist pseudo-rotation in a
      short-lived labile five-coordinated intermediate, involving initial attack on the
      labile coordination position trans to the sigma-bonded aryl. Bridge-cleavage
      reactions of the analogous bridged complexes occur similarly, but are much slower
      because of their ground-state stabilization and steric hindrance.

PMID- 15510292
TI  - Multinuclear platinum(II)-amine complexes containing bis(aminopropyl)dicarba
      closo-dodecaborane(12) ligands.
AB  - Treatment of the bridging bidentate 1,Z-bis(aminopropyl)-1,Z-dicarba-closo
      dodecaborane(12)(1,Z-bis(aminopropyl)-1,Z-carborane) ligands of the type 1,Z
      [H(2)N(CH(2))(3)](2)-1,Z-C(2)B(10)H(10)(L(1), Z= 7, 5) or (L(2), Z= 12, 6) with
      two equivalents of trans-[PtClI(2)(NH(3))](-), followed by halogen ligand
      metathesis with AgOTf and HCl((aq)) afforded the novel diplatinum(II)-amine
      species cis-[[PtCl(2)(NH(3))](2)L(n)](7(n= 1) or 8(n= 2), respectively).
      Similarly, the reaction of L(1) or L(2) with the labile trans
      [PtCl(dmf)(NH(3))(2)](+) afforded trans-[[PtCl(NH(3))(2)](2)L(n)](OTf)(2)(9(n= 1)
      or 10(n= 2), respectively) in good yield and purity. However, isolation of the
      analogous 1,2-carborane complexes was not possible owing to decomposition
      reactions that led to extensive degradation of the carborane cage and reduction
      of the metal centre. The mixed dinuclear complex [cis-[PtCl(2)(NH(3))]-L(1)-trans
      [PtCl(NH(3))(2)]]OTf (19) was prepared by treatment of the Boc-protected amine
      ligand 1-[(Boc)(2)N(CH(2))(3)]-7-[H(2)N(CH(2))(3)]-1,7-C(2)B(10)H(10)(L(3), 15)
      with trans-[PtCl(dmf)(NH(3))(2)](+) to yield trans-[PtCl(NH(3))(2)L(3)]OTf (16),
      followed by acid deprotection of the pendant amine group, complexation with trans
      [PtClI(2)(NH(3))](-), and halogen ligand metathesis using AgOTf and HCl((aq)). A
      novel trinuclear species containing 5 was prepared by the addition of two
      equivalents of 15 to the labile precursor cis-[Pt(dmf)(2)(NH(3))(2)](2+) followed
      by acid deprotection of the pendant amine groups. Further complexation with two
      equivalents of trans-[PtClI(2)(NH(3))](-) followed by halogen ligand metathesis
      using AgOTf and HCl((aq)) afforded the triplatinum(II)-amine species [cis
      [Pt(NH(3))(2)(L(1))(2)]-cis-[PtCl(2)(NH(3))](2)](OTf)(2)(23). Complexes 7-10, 19
      and 23 represent the first examples of multinuclear platinum(ii)-amine
      derivatives containing carborane cages. Preliminary in vitro cytotoxicity studies
      for selected complexes are also reported.

PMID- 15510293
TI  - Complexes of substituted derivatives of 2-(2-pyridyl)benzimidazole with Re(I),
      Ru(II) and Pt(II): structures, redox and luminescence properties.
AB  - N,N'-Chelating ligands based on the 2-(2-pyridyl)benzimidazole (PB) core have
      been prepared with a range of substituents (phenyl, pentafluorophenyl, naphthyl,
      anthracenyl, pyrenyl) connected to the periphery via alkylation of the
      benzimidazolyl unit at one of the N atoms. These PB ligands have been used to
      prepare a series of complexes of the type [Re(PB)(CO)(3)Cl],
      [Pt(PB)(CCR)(2)](where -CCR is an acetylide ligand) and
      [Ru(bpy)(2)(PB)][PF(6)](2)(bpy = 2,2'-bipyridine). Six of the complexes have been
      structurally characterised. Electrochemical and luminescence studies show that
      all three series of complexes behave in a similar manner to the analogous
      complexes with 2,2'-bipyridine in place of PB. In particular, all three series of
      complexes show luminescence in the range 553-605 nm (Pt series), 620-640 nm (Re
      series) and 626-645 nm (Ru series) arising from the (3)MLCT state, with members
      of the Pt(II) series being the most strongly emissive with lifetimes of up to 500
      ns and quantum yields of up to 6% in air-saturated CH(2)Cl(2) at room
      temperature. In the Re and Ru series there was clear evidence for inter-component
      energy-transfer processes in both directions between the (3)MLCT state of the
      metal centre and the singlet and triplet states of the pendant organic
      luminophores (naphthalene, pyrene, anthracene). For example the pyrene singlet is
      almost completely quenched by energy transfer to a Re-based MLCT excited state,
      which in turn is completely quenched by energy transfer to the lower-lying pyrene
      triplet state. For the analogous Ru(II) complexes the inter-component energy
      transfer is less effective, with (1)anthracene --> Ru((3)MLCT) energy transfer
      being absent, and Ru((3)MLCT)-->(3)anthracene energy transfer being incomplete.
      This is rationalised on the basis of a greater effective distance for energy
      transfer in the Ru(II) series, because the MLCT excited states are localised on
      the bpy ligands which are remote from the pendant aromatic group; in the Re
      series in contrast, the MLCT excited states involve the PB ligand to which the
      pendant aromatic group is directly attached, giving more efficient energy
      transfer.

PMID- 15510294
TI  - Aluminium alkyl and aryloxide complexes of pyrazine and bipyridines: synthesis
      and structure.
AB  - The reaction of AlMe(3) and [((t)Bu)(2)Al(micro-OPh)](2) with pyrazine (pyz),
      4,4'-bipyridine (4-4'-bipy), 1,2-bis(4-pyridyl)ethane (bpetha) and 1,2-bis(4
      pyridyl)ethylene (bpethe) yields (Me(3)Al)(2)(micro-pyz)(1), (Me(3)Al)(2)(micro
      4,4'-bipy)(2), (Me(3)Al)(2)(micro-bpetha)(3), (Me(3)Al)(2)(micro-bipethe)(4),
      Al((t)Bu)(2)(OPh)(pyz)(5), [((t)Bu)(2)Al(OPh)](2)(micro-4,4-bipy)(6a),
      [((t)Bu)(2)Al(OPh)](2)(micro-bpetha)(7a), [((t)Bu)(2)Al(OPh)](2)(micro
      bipethe)(8a). Compounds 1-4, 6a and 7a have been confirmed by X-ray
      crystallography. In solution compounds 1-4 undergo a rapid ligand-dissociation
      equilibrium resulting in a time-average spectrum in the (1)H NMR. In contrast,
      the solution equilibria for compounds 5-8a are sufficiently slow such that the
      mono-aluminium compounds may be observed by (1)H NMR spectroscopy:
      Al((t)Bu)(2)(OPh)(4,4-bipy)(6b), Al((t)Bu)(2)(OPh)(bpetha)(7b) and
      Al((t)Bu)(2)(OPh)(bpethe)(8b). The inability to isolate
      [((t)Bu)(2)Al(OPh)](2)(micro-pyz) and the relative stability of each complex is
      discussed with respect to the steric interactions across the bridging ligand (L)
      and the electronic effect on one Lewis acid-base interaction by the second Lewis
      acid-base interaction on the same ligand.

PMID- 15510295
TI  - Unprecedented double nucleophilic addition of a hydride at a central carbon of an
      eta3-allyl ligand.
AB  - Treatment of eta(3)-allyl compound [Cp(2)Mo(eta(3)-C(3)H(5))](+)(1; Cp =eta(5)
      C(5)H(5)) with MH (M = Li, Na) resulted in reduction of the allyl ligand to give
      propane. Deuterium-labeling studies were used to trace the origins and fates of
      the hydrogen atoms. The mechanism is discussed in light of the HSAB principle.
      The studies showed that the formation of propane can be explained by 1,2-hydrogen
      migration from the central to the terminal carbon of the allyl ligand, and the
      subsequent double nucleophilic addition of the hydride at the central carbon.

PMID- 15510296
TI  - Cyclometallated Pd(II) azido complexes containing 6-phenyl-2,2'-bipyridyl or 2
      phenylpyridyl derivatives: synthesis and reactivity toward organic isocyanides
      and isothiocyanates.
AB  - Cyclometallated palladium(II) azido complexes containing C,N,N- or C,N-donor
      ligands, [Pd(N(3))L](HL = 6-phenyl-2,2'-bipyridine or 2-phenylpyridyl
      derivatives), showed different reactivities toward organic isocyanides and
      isothiocyanates. In particular, aryl isocyanides (CN-Ar) underwent insertion into
      the orthometallated Pd-C bond on the phenyl moiety of the supporting ligand (L)
      in [Pd(N(3))L] or [Pd(N(3))(PR(3))L] to selectively give carbodiimido [[Pd(N=C=N
      Ar)L]], imidoyl [[Pd(N(3))(-C=N-Ar)(PR(3))L]], or imidoyl carbodiimido complexes
      [[Pd(N=C=N-Ar)(-C=N-Ar)L] or [Pd(N=C=N-Ar)(-C=N-Ar)(PR(3))L]], depending on
      reaction conditions. Interestingly, reactions of [Pd(N(3))(PR(3))L] with organic
      isothiocyanates gave unusual dinuclear complexes [(micro-SCN(4)-R)PdL](2),
      exhibiting the concurrent S- and N-coordinating thio-tetrazole bridge.

PMID- 15510297
TI  - Oxidative addition of silanes R3SiH to the unsaturated cluster [Os3(micro
      H)[micro3-Ph2PCH2PPh(C6H4)](CO)8]: evidence for reversible silane formation in
      the dynamic behaviour of [Os3(micro-H)(SiR3)(CO)9(micro-dppm)].
AB  - Oxidative addition of the silanes R(3)SiH (R(3)= Ph(3), Et(3), EtMe(2)) to the
      unsaturated cluster [Os(3)(micro-H)[micro(3)-Ph(2)PCH(2)PPh(C(6)H(4))](CO)(8)]
      leads to the saturated clusters [Os(3)(micro-H)(SiR(3))(CO)(9)(micro
      dppm)](SiR(3)= SiPh(3) 1, SiEt(3) 2 and SiEtMe(2)3) and the unsaturated clusters
      [Os(3)(micro -H)(2)(SiR(3))[micro(3)-Ph(2)PCH(2)PPh(C(6)H(4))](CO)(7)](SiR(3)=
      SiPh(3) 4, SiEt(3) 5 and SiEtMe(2)6). Structures are based on spectroscopic
      evidence and a XRD structure of [Os(3)(micro-H)(SiPh(3))(CO)(9)(micro-dppm)] 1 in
      which all non-CO ligands are coordinated equatorially and the hydride and the
      silyl groups are mutually cis. From variable-temperature (1)H NMR spectra of the
      SiEt(3) compound 2, exchange of the P nuclei is clearly apparent. Simultaneous
      migrations of the SiEt(3) group and of the hydride from one Os-Os edge to another
      generate a time-averaged mirror plane in the molecule. VT (1)H NMR spectra of the
      somewhat less bulky compound [Os(3)(micro-H)(SiMe(2)Et)(CO)(9)(micro-dppm)] 3
      have been analysed. Two isomers 3a and 3b are observed with the hydride ligand
      located on different Os-Os edges. Synchronous migration of the hydride and
      SiMe(2)Et groups is faster than the observed interconversion of isomers which
      occurs by hydride migration alone. The synchronous motion of H and SiR(3)only
      occurs when these ligands are mutually cis as in the major isomer 3a and we
      propose that this process requires the formation of a transient silane complex of
      the type [Os(3)(eta(2)-HSiR(3))(CO)(9)(micro-dppm)]. Turnstile rotation within an
      Os(CO)(3)(eta(2)-HSiR(3)) group leads to the observed exchange within the major
      isomer 3a without exchange with the minor isomer. This process is not observed
      for the minor isomer 3b because the hydride and the silyl group are mutually
      trans. Protonation to give [Os(3)(micro-H)(2)(SiR(3))(CO)(9)(micro-dppm)](+)
      totally suppresses the dynamic behaviour because there are no edge vacancies.

PMID- 15510298
TI  - Macrocyclic ligand design. Structure-function relationships involving the
      interaction of pyridinyl-containing, oxygen-nitrogen donor macrocycles with
      selected transition and post transition metal ions on progressive N-benzylation
      of their secondary amines.
AB  - Structure-function relationships underlying the interaction of progressively N
      benzylated N(4)O(2)-donor macrocycles with cobalt(II), nickel(II), copper(II),
      zinc(II), cadmium(II), silver(I) and lead(II) have been probed using a range of
      techniques that include X-ray diffraction, DFT computations, solvent extraction,
      potentiometric stability constant determinations and competitive membrane
      transport experiments. Collectively, the results indicate that N-benzylation of
      the secondary amine donor groups of the parent macrocyclic ring results in an
      enhanced tendency towards selectivity for silver(I) relative to the other six
      metals investigated. The observed behaviour serves as additional exemplification
      of the previously proposed concept of selective 'detuning' as a mechanism for
      metal ion discrimination.

PMID- 15510299
TI  - High-frequency EPR study of reduced diruthenium and dirhenium polypyridine
      complexes based on the 1,2,4,5-tetrazine radical bridge.
AB  - The radical complexes [(micro-L)[Ru(bpy)(2)](2)]*(3+), [(micro
      bmtz)[Ru(cym)Cl](2)]*(+) and [(micro-L)[Re(CO)(3)Cl](2)]*(-), where L are 3,6
      disubstituted 1,2,4,5-tetrazines such as 3,6-bis(2-pyrimidyl)-1,2,4,5-tetrazine
      (bmtz) and cym =p-cymene, were studied by X-band EPR in fluid solution and by 285
      GHz EPR in glassy frozen solution. A comparison with other transition metal
      complexes (Cu, Rh, Os, Ir, Pt) involving tetrazine radical ligands reveals that
      the g anisotropy reflects (i) the pi acceptor effect of the tetrazine
      substituents, (ii) the competition from ancillary pi acceptor ligands for back
      donation from the metal, and (iii) the spin-orbit coupling contributions from the
      transition metal.

PMID- 15510300
TI  - Syntheses, structures and antimicrobial activities of water-soluble silver(I)
      oxygen bonding complexes with chiral and racemic camphanic acid (Hca) ligands.
AB  - Water-soluble, relatively light-stable, chiral and achiral silver(I) complexes
      [[Ag(2)(ca)(2)]](n) and [[Ag(2)(ca)(2)(Hca)(2)]](n)(R- and S-Hca =(1R,4S)- and
      (1S,4R)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxylic acid,
      respectively) prepared from the reaction of Ag(2)O with chiral and racemic Hca in
      1:2 and 1:4 molar ratios were characterized by elemental analysis, TG/DTA, FTIR,
      and solution ((1)H, (13)C and (109)Ag) and solid-state ((13)C) NMR spectroscopy.
      Crystallography revealed that unique 2(1) helical polymer and zigzag structures
      were formed on self-assembly of the dimeric units in the crystals of [[Ag(2)(S
      ca)(2)]](n) and three [[Ag(2)(ca)(2)(Hca)(2)]](n). In the crystal of [[Ag(2)(S
      ca)(2)]](n) two 2(1) helices and a loop were observed in the stair-like polymer
      structure, whereas zigzag and a loop were seen in the crystals of three
      [[Ag(2)(ca)(2)(Hca)(2)]](n). Carbon NMR spectra in the solid state and in D(2)O
      indicated that these polymeric structures were loosely bound and fast ligand
      exchange reactions took place in aqueous solution. The complexes,
      [[Ag(2)(ca)(2)]](n) and [[Ag(2)(ca)(2)(Hca)(2)]](n), showed a wide spectrum of
      effective antimicrobial activity as anticipated for weak silver(i)-O bonding
      complexes. Similar antimicrobial activity of [[Ag(2)(ca)(2)]](n) and
      [[Ag(2)(ca)(2)(Hca)(2)]](n) against selected microorganisms suggested that ligand
      exchangeability played an important role as well as the coordination geometry of
      the silver(i) ion.

PMID- 15510301
TI  - Effect of the tether on the Mg(II), Ca(II), Cu(II) and Fe(III) stability
      constants and pM values of chelating agents related to EDDHA.
AB  - The effect of the length and the structure of the tether on the chelating ability
      of EDDHA-like chelates have not been established. In this work, PDDHA
      (propylenediamine-N,N'-bis(o-hydroxyphenyl)acetic acid), BDDHA (butylenediamine
      N,N'-bis(o-hydroxyphenyl)acetic acid) and XDDHA (p-xylylenediamine-N,N'-bis(o
      hydroxyphenyl)acetic acid) have been obtained and their chemical behaviour has
      been studied and compared with that of EDDHA following our methodology. The
      purity of the chelating agents, and their protonation, Ca(II), Mg(II), Fe(III)
      and Cu(II) stability constants and pM values have been determined. The stability
      constants and pM values indicate that EDDHA forms the most stable chelates
      followed by PDDHA. However, the differences among the pFe values are small when a
      nutrient solution is used, and in these conditions the XDDHA/Fe(III) chelate is
      the most stable. The results obtained in this work indicate that all the
      chelating agents studied can be used as iron chlorosis correctors and they can be
      applied to soil/plant systems.

PMID- 15510302
TI  - Synthesis and luminescence studies of mono- and C3-symmetric, tris(ligand)
      complexes of Sm(III), Y(III) and Eu(III) with sulfur-bridged binaphtholate
      ligands.
AB  - A series of trivalent mono- and tris(ligand) lanthanide complexes of a sulfur
      bridged binaphthol ligand [1,1'-S(2-HOC(10)H(4)Bu(t)(2)-3,6)(2)] H(2)L(SN), have
      been prepared and characterised both structurally and photophysically. The
      H(2)L(SN) ligand provides an increased steric bulk and offers an additional donor
      atom (sulfur) as compared with 1,1'-binaphthol (BINOL), a ligand commonly used to
      complex Lewis acidic lanthanide catalysts. Reaction of the diol H(2)L(SN) with
      [Sm[N(SiMe(3))(2)](3)] affords silylamido- and amino- derivatives
      [Sm(L(SN))[N(SiMe(3))(2)][HN(SiMe(3))(2)]] and the crystallographically
      characterised [Sm(L(SN))[N(SiMe(3))(2)](thf)(2)] with different degrees of
      structural rigidity, depending on the presence of coordinating solvents. The
      binaphthyl groups of the L(SN) ligand act as sensitisers of the metal centred
      emission, which is observed for the Eu(III) and Sm(III) complexes studied. We
      have therefore sought to use emission spectroscopy as a non-invasive technique to
      monitor a monomer-dimer equilibrium in these complexes. A dramatic difference
      between the emission properties of the unreactive dimeric Sm(III) aryloxide
      complex, the solvated monomeric analogues and the amido adduct demonstrated the
      potential use of such a technique. For a few representative lanthanides (Ln = Sm,
      Eu and Y) the reaction of the dilithium salt Li(2)L(SN) with either
      [Ln[N(SiMe(3))(2]3)] or [LnCl(3)(thf)(3)] affords only the homoleptic complex
      [Li(S)(3)][LnL(SN)(3)](S = thf or diethyl ether); we report the structural
      characterisation of the Sm complex. However, the reactions of this dipotassium
      salt K(2)L(SN) with [Sm[N(SiMe(3))(2)](3)] or [SmCl(3)(thf)(3)] give only
      [SmL(SN)N(SiMe(3))(2)], or intractable mixtures respectively, in which no
      (tris)binaphtholate is observed. The only isolable lanthanide-L(SN) halide adduct
      so far is [YbL(SN)I(thf)].

PMID- 15510303
TI  - Dinuclear N-heterocyclic carbene complexes of silver(I), derived from imidazolium
      linked cyclophanes.
AB  - The synthesis of four new silver complexes of bidentate N-heterocyclic carbenes,
      derived from imidazolium-linked cyclophanes, has been achieved via a simple
      complexation reaction of the imidazolium-linked cyclophanes with the basic metal
      source Ag(2)O. The cyclophane structures contain two imidazolyl links between
      ortho-, meta- and mixed ortho/meta-substituted aromatic rings. The new silver
      carbene systems are thermally stable and have been characterised by NMR
      spectroscopy and X-ray crystallography. Three of the complexes have a dimeric
      structure of the form [L(2)Ag(2)](2+) in the solid state that is rigid on the NMR
      timescale in solution. The fourth complex has a neutral structure of the form
      [L(AgBr)(2)], the NMR studies suggesting some lability of the L-Ag bonding in
      solution.

PMID- 15510304
TI  - Experimental investigations and ab initio studies of selenium(II)
      dialkanethiolates, Se(SR)2.
AB  - Selenium(II) dimethanethiolate, Se(SMe)(2), was synthesized by reaction of SeO(2)
      with HSMe. Basic spectroscopic data for Se(SMe)(2) and selenium(II) bis(2-methyl
      2-propanethiolate), Se(S(t)Bu)(2), were recorded and interpreted with the support
      of ab initio calculations. Both compounds are thermodynamically unstable
      relatively to selenium and the corresponding disulfide. The UV/vis spectra of
      both compounds are qualitatively similar, the two bands being attributed to n(Se)
      sigma*(Se-S) transitions. The bands at 369 and 397 cm(-1) in the IR spectra of
      Se(SMe)(2) and Se(S(t)Bu)(2), respectively, are assigned to nu(as)(SeS(2)). The
      (77)Se NMR shifts of Se(SMe)(2)(784 ppm) and Se(S(t)Bu)(2)(556 ppm) differ
      substantially from each other and show positive temperature gradients.
      Calculations at the GIAO-HF/962+(d) level reproduced the difference of the (77)Se
      NMR chemical shifts between Se(SMe)(2) and Se(S(t)Bu)(2). At the same level, the
      effect of conformational changes on (77)Se shifts were studied for Se(SMe)(2). In
      the solid state Se(SMe)(2) forms long intermolecular SeS contacts while
      Se(S(t)Bu)(2) does not. Both compounds exhibit anti-conformations of the methyl
      and tert-butyl groups with respect to the SeS(2) plane. MP2/LANL2DZ(d) geometry
      optimizations, single point energy and frequency calculations performed for
      Se(SMe)(2) show, that syn- (C(s)) and anti-conformers (C(2)) represent minima on
      the potential energy surface, the latter being by 8 kJ mol(-1) lower in energy
      than the former. Both conformers are stabilized by intramolecular pi-type n(S(1))
      sigma*(Se-S(2)) orbital interactions. The energy of the transition state for the
      mutual conversion of the two conformers was calculated to be 31 kJ mol(-1) above
      that of the syn conformer, allowing a rapid interconversion of the two conformers
      at room temperature. Intermolecular interactions between Se(SMe)(2) molecules
      were also studied by means of calculations at the MP2/LANL2DZ(d) level. For
      Se(S(t)Bu)(2) MP2/LANL2DZ(d) geometry optimizations and single point energy
      calculations revealed a C(2)-symmetric anti- and a C(1) symmetric syn-conformer,
      the latter being 21 kJ mol(-1) higher in energy than the former. Se(SMe)(2) and
      Se(S(t)Bu)(2) exchange thiolate groups with other selenium(II) dithiolates,
      tellurium(II) dithiolates and with thiols, if catalytic amounts of p
      CH(3)C(6)H(4)SO(3)H are added.

PMID- 15510305
TI  - A new bis(3-hydroxy-4-pyridinone)-IDA derivative as a potential therapeutic
      chelating agent. Synthesis, metal-complexation and biological assays.
AB  - A new bis(3-hydroxy-4-pyridinone) derivative of iminodiacetic acid, imino
      bis(acetyl(1-(3'-aminopropyl)-3-hydroxy-2-methyl-4-pyridinone)), IDAPr(3,4
      HP)(2), has been prepared and studied in its interaction with a set of hard metal
      ions. This tetradentate ligand presents a much higher chelating efficiency for
      trivalent hard metal ions (Fe, Ga, Al) than the monodentate derivative
      Deferriprone, namely at the diluted conditions prevailing in physiological
      conditions and at low clinical doses. A similar behaviour was also observed for
      the complexation with Zn(II) but at a significantly lower extent. This compound
      presents a moderate hydrophilic character at physiological pH (logD=-1.72). In
      vivo assays showed much more rapid clearance of (67)Ga from most tissues of metal
      loaded mice than the drug Deferriprone and the radioactivity excretion occurs
      mostly through the kidneys. Therefore, results from in vitro and in vivo studies
      indicated good perspectives for this compound to be a potential decorporating
      agent for hard metal ions in overload situations without depletion of essential
      metal ions such as zinc.

PMID- 15510306
TI  - 1,3,5-Triazine-based tricopper(II) complexes: structure and magnetic properties
      of threefold-symmetric building blocks.
AB  - Two new trinuclear complexes 1 and 2 that are composed of the three-directional
      ligand 2,4,6-tris(di-2-pyridylamino)-1,3,5-triazine (dipyatriz) and copper(II)
      chloride as well as a 1D polymeric zigzag system 3 assembled from trimetallic
      type 2 building blocks have been prepared and structurally characterized. While
      the triazine-N are not involved in metal coordination, each ligand bidentately
      binds to three copper ions via its three pairs of pyridine-N donors, and five
      coordination of the copper is completed by chloride or dmso solvent molecules.
      Variable-temperature magnetic studies reveal weak antiferromagnetic coupling.
      Magnetic properties of the trinuclear entities and of the bis(micro-chloro)
      bridged pseudo-dimeric copper(II) subunits in 3 can be rationalized on the basis
      of the structural findings.

PMID- 15510307
TI  - Roles of a tetrahydroborate ligand in a facile route to ruthenium(II) ethyl
      hydride complexes, and a kinetic study of ethane reductive elimination.
AB  - The tetrahydroborate ligand in [Ru(eta(2)-BH(4))(CO)H(PMe(2)Ph)(2)], 1, allows
      conversion under very mild conditions to [Ru(CO)(Et)H(PMe(2)Ph)(3)], 7, by way of
      [Ru(eta(2)-BH(4))(CO)Et(PMe(2)Ph)(2)], 4. Deprotection of the hydride ligand in
      7(by BH(3) abstraction) occurs only in the final step, thus preventing premature
      ethane elimination. A deviation from the route from 4 to 7 yields [Ru(eta(2)
      BH(4))(COEt)(PMe(2)Ph)(3)], 6, but does not prevent ultimate conversion to 7.
      Modification of the treatment of 4 yields an isomer of 7, 10. Both isomers
      eliminate ethane at temperatures above 250 K: the immediate product of
      elimination, thought to be [Ru(CO)(PMe(2)Ph)(3)], 11, can be trapped as
      [Ru(CO)(PMe(2)Ph)(4)], 12, [Ru(CO)H(2)(PMe(2)Ph)(3)], 3a, or [Ru(CO)(C[triple
      bond]CCMe(3))H(PMe(2)Ph)(3)], 13. The elimination is a simple first-order process
      with negative DeltaS(++) and (for 7) a normal kinetic isotope effect (k(H)/k(D)=
      2.5 at 287.9 K). These results, coupled with labelling studies, rule out a rapid
      equilibrium with a [sigma]-ethane intermediate prior to ethane loss.

PMID- 15510309
TI  - Update on endoscopic cervical surgery.
AB  - The onset of cervicoscopy dates back to the first laparoscopic parathyroidectomy
      in 1996. This operation, with its several variants, has today become a valid
      option that is widespread in many centers. Endoscopic or video-assisted
      thyroidectomy was introduced later, despite the limits imposed by the mass of the
      gland to be removed. Even though it was indicated for a minority of patients for
      this reason, both parathyroidectomy and thyroidectomy showed some important
      advantages with respect to conventional surgery, advantages that were also
      demonstrated in prospective studies that include a better cosmetic outcome and a
      less distressful postoperative course. These approaches proved to be safe and
      feasible in any surgical background, and their complication rate is the same as
      traditional open neck surgery. The videoscopic access to neck lymph nodes
      (central and lateral compartments) seems to be very promising, whereas other
      fields of application such as carotid artery surgery and spine surgery are still
      being studied experimentally. Cervicoscopy by consequence has to be considered an
      important surgical tool that can be further improved but which also has an
      excellent potential.

PMID- 15510310
TI  - Minimally invasive esophageal resection.
AB  - Esophagus resection is the adequate treatment for some benign esophageal
      diseases, especially caustic and peptic stenosis and end-stage motility
      dysfunction. However, the most frequent indications for esophageal resection are
      the high-grade dysplasia of Barrett esophagus and nonmetastasized esophageal
      cancer. Different procedures have been developed to perform esophageal resection
      given the 5-year survival rate among operated patients of only 18%. The
      disadvantage of the conventional approach is the high morbidity rate, especially
      with pulmonary complications. Minimally invasive esophageal resections, which
      were first performed in 1991, may reduce this important morbidity and preserve
      the oncologic outcome. The first reports of morbidity and respiratory
      complications with this approach were discouraging and it seemed likely that the
      procedure would have to be abandoned. However, in the last 5 years, an important
      impetus for these techniques was given by Japanese groups and the group of
      Luketich in Pittsburgh. The outcomes of these new series are different than those
      of the beginning period, leading to an enormous expansion worldwide. Important
      factors for this change are the standardization of the operative technique, the
      experience of many surgeons with more advanced laparoscopic procedures, important
      improvements in instruments for dissection and division of tissues, a better
      anesthesia technique, and a better selection of patients for operation. Two
      minimally invasive techniques are being perfected: the three-stage operation by
      right thoracoscopy and laparoscopy, and the transhiatal laparoscopic approach. It
      seems that the first approach may be applied successfully for any tumor in the
      esophagus, whereas the transhiatal seems ideal for distal esophageal and
      esophagogastric junction tumors. This review paper discusses all these aspects,
      with special attention for indications and operative technique.

PMID- 15510311
TI  - The massive hiatal hernia: dealing with the defect.
AB  - The success of laparoscopic fundoplication has extended the use of the
      laparoscopic approach to treating more difficult situations such as
      paraesophageal hernias (PEHs) or type III (mixed) hiatal hernia. The results have
      shown that laparoscopic repair is feasible and safe. However, several series have
      shown recurrence rates of up to 42% as a result of difficulty in the closure of
      the hiatal gap. Some authors recommend the use of prosthetic mesh to reinforce
      the hiatal closure. This review analyses the different techniques proposed to
      prevent recurrence after laparoscopic repair of PEHs. The information currently
      available shows that the use of a mesh for hiatal repair is safe and prevents
      recurrence. However, data on the long-term results are lacking, and infrequent
      but severe complications may arise. The mesh should be used selectively, and the
      decision to proceed should be based on clinical experience.

PMID- 15510312
TI  - The gastrojejunostomy in laparoscopic Roux-en-Y gastric bypass.
AB  - Many techniques for creating the gastrojejunal anastomosis while performing
      laparoscopic gastric bypass in obese patients have been described. The stapled
      anastomoses comprise the circular stapler technique, using either a 21- or a 25
      mm anvil, and the linear stapler technique. The handsewn anastomosis, which seems
      to offer some advantages over the mechanical technique, is being performed with
      increased frequency. The three techniques are described here and discussed in the
      light of our own experience.

PMID- 15510313
TI  - Laparoscopic distal pancreatomy: are we ready for a standardized technique?
AB  - This paper describes and discusses the surgical steps needed to perform a
      laparoscopic distal pancreatectomy. The current lack of standardization of the
      operative technique can account for the limited diffusion of this procedure. The
      issue of spleen preservation, which cannot be overemphasized, always demands an
      accurate surgical technique that results from proficiency both in open pancreatic
      surgery and advanced laparoscopy. The preservation of the splenic vessels or
      short gastric-vessel salvage is feasible, yet with different indications. Also,
      the splenic-vessels preservation procedure has two distinct technical options.
      The technique of occlusion of the pancreatic stump is crucial for reducing the
      risk of a postoperative fistula and should be tailored to the structural features
      of the gland at the transection line. Finally, the hand-assisted approach can
      provide distinctive advantages over the pure laparoscopic technique in selected
      circumstances.

PMID- 15510314
TI  - Is the laparoscopic approach reasonable in cases of splenomegaly?
AB  - Laparoscopic splenectomy in cases of splenomegaly has been shown to be feasible
      in experienced hands, even though the size of the spleen increases the operative
      time and difficulty. Laparoscopic splenectomy for splenomegaly offers the same
      advantages as for patients with smaller spleens: a shorter hospital stay and a
      faster recovery. Recent experience has shown that hand-assisted laparoscopic
      surgery makes the surgical maneuvers during laparoscopic splenectomy in cases of
      splenomegaly considerably easier while preserving the advantages of a purely
      laparoscopic approach. This technique may facilitate and broaden the application
      of laparoscopy for splenectomy in patients with enlarged spleens.

PMID- 15510315
TI  - Laparoscopic ventral hernia repair: advances and limitations.
AB  - Laparoscopic ventral hernia repair, a topic of great debate today, has evolved to
      be a feasible and safe procedure. It has been shown to be as effective as open
      repair, with a lower recurrence rate. Despite the excellent results of the
      laparoscopic repair of ventral hernias, numerous controversies are associated
      with this procedure, such us how to create the pneumoperitoneum, how to perform
      adhesiolysis, how to manage the hernia sac, the evolution and complications
      related to postoperative seroma, the type and size of the mesh, and how to insert
      and fix the mesh. This paper addresses many of these issues and provides data
      about the advances and limitations associated with laparoscopic ventral hernia
      repair, together with the description of our results. Also analyzed are future
      aspects of laparoscopic ventral hernia repair related to prosthetic materials and
      methods of fixation, especially those regarding bioactive materials and
      biosurgery.

PMID- 15510316
TI  - Energy sources in laparoscopy.
AB  - Traditional monopolar and bipolar electrosurgery remain very useful in
      laparoscopic surgery. The need for meticulous hemostasis and the tedium of vessel
      ligation in advanced cases has propelled the development of new energy source
      devices that have proved to be remarkably helpful in both laparoscopic and open
      surgery. Energy sources in the form of argon beam coagulation, ultrasonic
      coagulation, and bipolar vessel sealing systems have revolutionized laparoscopic
      surgery. Although each of these energy sources has improved the efficiency and
      safety of minimally invasive techniques, they can also be associated with
      distressing complications. This report describes the biophysics of these tools,
      their spectrum of effectiveness, and methods of application that may improve our
      ability to perform surgery in a safe and proficient manner.

PMID- 15510317
TI  - An experimental operating room project for advanced laparoscopic surgery.
AB  - With the challenges that the health sector now faces in accordance with
      readjustments and demands for increased efficiency, resource utilization, and
      innovation, we have initiated a project to develop the future operating room for
      advanced laparoscopic surgery. New hospitals are being built that contain
      numerous operating room theaters. To share experiences and avoid repeating the
      same mistakes as others, we find it suitable to build an "experimental" operating
      room theater where we can try out and study new equipment, logistics, and
      communications, and operating forms and new technology that both benefit the
      establishment of our hospital, as well as the establishment of other hospitals
      and their laparoscopic operating rooms nationally and internationally. The main
      goals in the project are, through research and development, to reveal information
      and develop technology and methods to establish more efficient and prospective
      patient treatment that is focused on quality. The project is deeply rooted in the
      established research environment in Trondheim, Norway. We will develop new
      integrated solutions in the laparoscopic operating unit to create a possibility
      to rapidly implement the results in the form of practical improvements, increased
      quality, and renovation in patient treatment. The goal is also that this will
      result in the establishment of new industry nationally.

PMID- 15510318
TI  - Recommending physical activity to patients.

PMID- 15510319
TI  - Reviving the ECG series.

PMID- 15510320
TI  - Edward Jenner (1749-1823): conqueror of smallpox.

PMID- 15510321
TI  - Outpatient preanaesthesia evaluation clinics.
AB  - In recent years, there has been a paradigm shift from an inpatient to outpatient
      preanaesthesia evaluation. This has been driven by rising healthcare costs and
      the increasing popularity of ambulatory and same-day admission surgery. These
      outpatient preanaesthesia clinics play an important role in enhancing the cost
      effectiveness of the perioperative process. This review describes the structure
      of modern outpatient preanaesthesia evaluation clinics, and the associated
      benefits, limitations and controversies.

PMID- 15510322
TI  - Physical activity patterns of Singaporeans in 2001.
AB  - INTRODUCTION: This study was conducted on Singaporean males and females to
      determine the extent of involvement in sport, work-based and home-based physical
      activities, and other activities such as walking and stairclimbing. METHODS: A
      Physical Activity Questionnaire was designed and data collected in conjunction
      with the Singapore National Sports Participation Survey 2001. RESULTS: Three
      hundred and ten households with 605 respondents (287 males and 318 females)
      completed the questionnaire, representing a response rate of 81 percent. Males
      spent more time doing sports, work-based physical activity and walking and
      stairclimbing activities while females spent more time in housework. However,
      females spent more time (568 versus 410 minutes per week) on overall physical
      activity, mainly due to their heavier involvement in housework. Compared with a
      similar study in 1997, males and females were doing more sports activities and
      walking and stairclimbing activities, but had reduced involvement in work-based
      and home-based activities. Overall, respondents in 2001 were spending about 31
      percent less time (457 versus 598 minutes per week) on physical activities than
      respondents in 1997. There was a reduction in physical activities among males
      from 476 minutes per week to 410 minutes per week, and a sharper drop among
      females from 904 minutes per week to 567 minutes per week. CONCLUSION:
      Singaporean males and females in 2001 are spending less time on overall physical
      activities. The trend towards a reduction in overall physical activities from
      1997 to 2001 is cause for concern. Relevant organisations would, therefore, need
      to continue promoting sports and physical activities to the Singapore population.

PMID- 15510323
TI  - Factors associated with poorly-controlled hypertension in continuous ambulatory
      peritoneal dialysis patients.
AB  - INTRODUCTION: Hypertension is highly prevalent among continuous ambulatory
      peritoneal dialysis (CAPD) patients and is a major risk factor for cardiovascular
      complications. This study examines the risk factors associated with poorly
      controlled hypertension in CAPD. METHODS: We performed a cross-sectional study of
      66 stable adult CAPD patients to evaluate their hypertension control over a
      period of three to four months and their associations with other clinical and
      laboratory parameters. RESULTS: The mean age of the patients was 56.7 (plus or
      minus 1.27) years. Their mean systolic and diastolic blood pressure were 139
      (plus or minus 2.59) mmHg and 77 (plus or minus 1.35) mmHg respectively; 71
      percent of them were on antihypertensive drugs. Thirty (45.5 percent) patients
      had high blood pressure greater than 140/90mmHg. Compared with patients with
      normal blood pressure, patients with high blood pressure received significantly
      more antihypertensive drugs (p-value equals 0.034) and were more likely to be
      clinically overloaded (p-value less than 0.001). Multivariate analysis showed
      that systolic blood pressure was predicted by volume expansion (p-value less than
      0.001) while diastolic blood pressure was negatively predicted by age (p-value
      equals to 0.004). In addition, volume overload was predicted positively by
      dialysate/plasma creatinine (p-value equals 0.011) and negatively by serum
      albumin (p-value less than 0.001). CONCLUSION: Clinically-apparent volume
      overload was associated with poor systolic blood pressure control despite
      aggressive antihypertensive drug therapy. This finding underlines the importance
      of fluid control and could provide an explanation of the poor outcome observed in
      patients with high peritoneal transport.

PMID- 15510324
TI  - Infective endocarditis in childhood: a seven-year experience.
AB  - INTRODUCTION: The epidemiology, clinical features, treatment and outcomes of
      infective endocarditis (IE) are reviewed. METHODS: A retrospective descriptive
      study was performed involving patients treated for IE at a paediatric tertiary
      centre in Singapore, between May 1997 and April 2004. Duke criteria were used to
      retrospectively evaluate the diagnosis of IE in these cases. Data analysis was
      performed using SPSS for Windows. RESULTS: There were a total of 27 children with
      IE in the seven-year study period. Of these, 24 (88.9 percent) had congenital
      heart disease, one had rheumatic valvular heart disease and two had normal
      anatomy. Fever (81.5 percent) was the primary presenting symptom, while
      splenomegaly (40.7 percent) and septic spots (22.2 percent) were the most common
      physical findings. C-reactive protein was raised in all cases with a mean of
      100.1mg/L. Blood cultures were positive in 77.8 percent of cases and the most
      common organism identified was Viridans Streptococcus species (25.9 percent).
      Vegetations were detected on echocardiography in 55.5 percent of cases. According
      to the Duke criteria, 48.1 percent of our patients fulfilled the clinical
      diagnosis of definite IE and 51.9 percent had possible IE. The median duration of
      parenteral antibiotics was 31 days. Major complications were seen in seven (25.9
      percent) patients, of whom five had either left heart vegetations or a right-to
      left shunt physiology. CONCLUSION: IE is an uncommon infection in childhood and
      occurs primarily in patients with congenital heart disease. Rheumatic heart
      disease is rarely a predisposing cause in our local children. Early diagnosis of
      IE is challenging and depends on a high index of suspicion. Useful clues include
      the presence of splenomegaly, septic emboli, microscopic haematuria and high C
      reactive protein level greater than 100mg/L. The Duke criteria for the diagnosis
      of IE are relevant locally, but if modified with an expanded list of minor
      criteria including the above useful clues, may increase the sensitivity of
      diagnosing definite IE. The presence of left-sided heart vegetations is a strong
      predictor of complications and must be treated aggressively.

PMID- 15510325
TI  - Liver injury induced by the non-steroidal anti-inflammatory drug mefenamic acid.
AB  - INTRODUCTION: Non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat
      musculoskeletal disorders, inflammation and to control pain. Virtually all NSAIDs
      are capable of producing liver injury ranging from mild reversible elevation of
      liver enzymes to severe hepatic necrosis. METHODS: Mice were dosed
      intraperitoneally with mefenamic acid either one day at 100mg/kg and 200mg/kg, or
      14 days dosing at 50mg/kg/day and 100mg/kg/day. Plasma was taken for alanine
      aminotransferase activity. Mice were sacrificed at the end of the study. Livers
      were removed and weighed. Liver samples were taken for histology. results: One
      day doses of mefenamic acid revealed dose-dependent hepatocyte degeneration in
      the liver parenchyma. There were no significant changes in plasma alanine
      aminotransferase activity. Interestingly, 14-day daily doses induced
      hepatocellular necrosis, massive degeneration and inflammation. This was
      accompanied by a significant increase in plasma alanine aminotransferase activity
      and significant increase in the liver weight in the 100mg/kg/day mefenamic acid
      dosed mice. CONCLUSION: Results from this study suggest that mefenamic acid is
      capable of producing hepatotoxicity and care should be taken when prescribing or
      using this drug.

PMID- 15510326
TI  - Clip-induced biliary stone.
AB  - Surgical clip migration is a well-known phenomenon ever since their first use in
      surgery. The mechanism of clip migration is poorly understood, and can occur from
      days to years after laparoscopic cholecystectomy. Migration of the surgical clips
      may be a complex process involving necrosis, pressure exerted from intra
      abdominal movement, formation of stones over the exposed clip within the bile
      duct, and eventual migration into the common bile duct. We report two cases, a 58
      year-old man and a 54-year-old woman, of clip- induced biliary stones resulting
      from surgical clip migration a few years after laparoscopic cholecystectomy.

PMID- 15510327
TI  - Chronic inflammatory demyelinating polyneuropathy in a child: clinical-spinal MR
      imaging correlation.
AB  - Spinal magnetic resonance (MR) imaging of a 3-year-old girl with chronic
      inflammatory demyelinating polyneuropathy (CIDP) showed thickened and marked
      enhancement of the lumbosacral nerve roots. These abnormalities resolved after
      steroid treatment. MR imaging of the cauda equina may be helpful in the diagnosis
      of CIDP.

PMID- 15510328
TI  - Electrocardiographical case. Asymptomatic patient with ST-segment elevation.
AB  - A 46-year-old man complained of recurrent episodes of giddiness which was not
      associated with chest pain or breathlessness. There was no family history of
      sudden death. Clinical examination was unremarkable.12-lead electrocardiogram
      (ECG) showed ST segment elevation in the right precordial leads, with coved ST
      segment elevation at its J point followed by a negative T wave with no
      isoelectric separation, specifically in V2. These ECG features are characteristic
      of the Brugada syndrome. He underwent a flecanide challenge which produced
      further elevation of ST segment at its J point and spontaneous ventricular
      ectopy. Electrophysiological studies induced ventricular fibrillation with 3
      extra stimuli. An implantable cardioverter-defibrillator was implanted for
      prevention of sudden cardiac death. The Brugada syndrome is discussed.

PMID- 15510329
TI  - Clinics in diagnostic imaging (101): Multinodular accessory thyroid tissue.
AB  - A 71-year-old woman with a strong family history of thyroid cancer presented with
      3 months of constipation. A carcinoid tumour of the rectum was found at
      colonoscopy. On physical examination, she had a large goitre and there was a 3-4
      cm firm submental mass. The differential diagnosis was accessory thyroid tissue
      or a carcinoma metastasis. Staging computed tomography was performed to include
      the neck, followed by ultrasonography and aspiration biopsy of the submental
      mass, which confirmed the diagnosis of multinodular accessory thyroid tissue.
      Differences in aetiology and pathophysiology of accessory thyroid tissue and
      ectopic thyroid glands are discussed.

PMID- 15510331
TI  - Insights into the future generation of veterinarians: perspectives gained from
      the 13- and 14-year-olds who attended Michigan State University's veterinary
      camp, and conclusions about our obligations.
AB  - Veterinary medicine is at a crossroads: the future of the profession will be
      determined by those who join it and by those who select who will join it.
      Veterinary schools are the gatekeepers of the profession, and the entire
      veterinary profession is responsible for ensuring that the image it presents to
      those who will join it matches the social needs that it must serve. The
      application process for a Michigan State University College of Veterinary
      Medicine (MSUCVM) academic summer camp provided an opportunity to discern
      attributes of the 314 eighth-grade students who attended in 2000-2002. A re
      reading of their application essays allowed clustering of similar descriptions
      and comments about motivations to attend the camp, interests in science,
      interactions with animals, and exposure to veterinarians and veterinary medicine.
      Many veterinary camp attendees will be undergraduate students by 2005/2006 and
      will be applying to colleges of veterinary medicine between 2008 and 2010. There
      fore, an understanding of their attributes is germane to discussions about
      desirable characteristics of veterinary college applicants. Although the camp was
      designed to attract eighth graders interested in science and curious about
      veterinary medicine, attendees frequently described veterinary medicine as their
      career goal. These students (89.5% female, 95.6% residents of Michigan) enjoyed
      science, but their interest in veterinary medicine related to emotions such as a
      love of animals and sympathy for sick or injured animals (96.1%). They discussed
      having pets in their homes (75.5%), involvement with horseback riding (20.7%),
      experiences with animal-related projects and activities in 4-H (17.2%), and
      husbandry experience at farms or stables (16.2%). Although 22.6% had already
      shadowed a veterinarian and 12.8% described receiving other forms of veterinary
      mentoring, 22.9% commented on their inability to gain shadowing exposures prior
      to age 16. Based on the results of this survey and years of working with
      adolescents interested in veterinary medicine, the author offers conclusions
      about mentoring youth with an interest in veterinary careers.

PMID- 15510332
TI  - General panorama of European veterinary education.

PMID- 15510333
TI  - The Bologna Treaty: a contribution to the development of quality education in
      Europe.

PMID- 15510334
TI  - Future directions in the European union for veterinary education as related to
      food-producing animals, with special reference to Greece.
AB  - During the past 50 years, procedures for raising food-producing animals have
      changed. Intensification of food production was necessary to keep prices low and
      to fulfill market demands for the continuously increasing worldwide population.
      Intensification of farming procedures produced many new problems, some of which
      had a considerable impact on public opinion about how animals are raised and how
      food of animal origin is produced and preserved. "Man made diseases" of animals
      such as bovine spongiform encephalopathy (BSE); contamination of foods with
      dioxins either through contamination of animal feeds or from the environment; and
      increased microbial resistance to drugs used for treatment, for prophylaxis of
      animals from infectious agents, and for growth promotion are some well-known
      hazards of intensified farming. Veterinarians working on food-producing animals
      are faced with an increased demand for foods of high quality and safety in
      developed countries, and higher quantities in the rest of the world. These
      qualitative and quantitative changes indicate that they must adjust to these new
      conditions. They will be most successful if their education is adjusted to meet
      the challenges that the public has created for them through new concepts of the
      production of food of animal origin. One such concept is the production of foods
      under fully certified procedures from the farm to the consumer's table. Food
      safety measures protecting public health will better be achieved if the education
      of the future veterinarian includes the principles of Hazard Analysis Critical
      Control Points (HACCP) starting at farm level. This article provides some market
      driven ideas in this direction for European Union (EU) countries, including
      Greece.

PMID- 15510335
TI  - The veterinary education program of the University of Veterinary Medicine Vienna,
      Austria.

PMID- 15510336
TI  - Curriculum development in the Netherlands: introduction of tracks in the 2001
      curriculum at Utrecht University, The Netherlands.
AB  - The Faculty of Veterinary Medicine in Utrecht has recently introduced two major
      curriculum changes in order to keep pace with developments in research (the vast
      increase in scientific knowledge), in society (the quality awareness of
      veterinary clients), and in the veterinary profession, where a species and sector
      differentiation can be observed. After about 15 years during which the curriculum
      remained more or less unchanged, a radical curriculum revision was introduced in
      1995. A further revision, with the introduction of separate study tracks, began
      in 2001. The 2001 curriculum focuses on academic and scientific training, active
      learning and problem solving, training in communication and professional
      behavior, and lifelong learning. It is divided into a four-year core curriculum,
      in which a broad, cross-species pathobiological insight is central, and a two
      year track curriculum, through which students achieve a starting competence in a
      specific species or sector. The main teaching methods are tutorials and group
      tasks; practical work is used mainly to achieve specific veterinary skills.
      Teaching hours represent 30-35% of all study hours. Self-teaching is encouraged
      by providing study materials, self-teaching questions, teachers assigned to
      assist with self-teaching, and adequate facilities. The five tracks offered are
      Companion Animals/Equine; Food Animals; Veterinary Public Health; Veterinary
      Research; and Veterinary Administration and Management. All students follow a
      uniform 30-week clinical rotation program, while the track program is 42 weeks. A
      summary of admission procedures is given, as well as the times and procedures for
      track selection.

PMID- 15510337
TI  - The new veterinary curriculum at Ghent University.

PMID- 15510338
TI  - Veterinary education in Germany.

PMID- 15510339
TI  - Observations of veterinary medicine students' approaches to study in pre-clinical
      years.
AB  - RATIONALE FOR THIS STUDY: This study has two purposes. The first is to explore an
      instrument of evaluation of the approaches to study (deep, strategic, and
      surface) adopted by students in the pre-clinical years of their veterinary degree
      program. The second is to examine relationships between these approaches and a
      broad range of further factors deemed relevant to the veterinary medicine
      context. We envisage that a greater knowledge of how these students learn will
      aid curriculum reform in a way that will enrich the learning experience of
      veterinary students. METHODOLOGY: A questionnaire consisting of the 52-question
      Approaches to Study Inventory (ASI) and an additional 49 questions relating
      mainly to teaching, assessment, and study skills was distributed to 215
      veterinary medicine (MVB) students in their pre-clinical years of study. Factor
      analysis was used to ensure that the ASI section of the questionnaire maintained
      previously reported structure. The internal reliability of the approaches
      measured was tested using Cronbach alpha analysis. The approaches were described
      as frequency distributions. Associations between the parameters (deep, strategic,
      and surface) and 49 additional context-specific factors were investigated using
      loglinear analysis. RESULTS: (1) Factor analysis revealed that the integrity and
      structure of the instrument in this context was generally comparable to previous
      studies. (2) The impact of a high workload was evident in the surface approach,
      with fear of failure becoming a strong motivating factor and syllabus boundness a
      widely used strategy. (3) Associations made between the approaches and 49 context
      specific factors showed strong associations between both workload and lack of
      prior knowledge with the surface approach. (4) Grades were associated positively
      with both the deep and strategic approaches but negatively with the surface
      approach. (5) A range of learning and study skills were associated positively
      with the deep and strategic approaches and negatively with the surface approach.
      CONCLUSION: The ASI proved to be a reliable and insightful instrument,
      highlighting specific surface learning tendencies present in the group as well as
      a deep learning approach, the pattern of which deviates from previous studies on
      this subject. This study also confirms the value of some teaching practices as a
      means of supporting deep learning and perhaps challenging surface learning
      strategies. The prevalent perception of a high workload is notable, as is its
      positive association with surface learning.

PMID- 15510340
TI  - An attempt to estimate students' workload.
AB  - Following the recent introduction of the European Credit Transfer System (ECTS)
      into several European university programs, a new interest has developed in
      determining students' workload. ECTS credits are numerical values describing the
      student workload required to complete course units; ECTS has the potential to
      facilitate comparison and create transparency between institutional curricula.
      ECTS credits are frequently listed alongside institutional credits in course
      outlines and module summaries. Measuring student workload has been difficult; to
      a large extent, estimates are based only upon anecdotal and casual information.
      To gather more systematic information, we asked students at the Veterinary
      Faculty, University of Ljubljana, to estimate the actual total workload they
      committed to fulfill their coursework obligations for specific subjects in the
      veterinary degree program by reporting their attendance at defined contact hours
      and their estimated time for outside study, including the time required for
      examinations and other activities. Students also reported the final grades they
      received for these subjects. The results show that certain courses require much
      more work than others, independent of credit unit assignment. Generally, the
      courses with more contact hours tend also to demand more independent work; the
      best predictor of both actual student workload and student success is the amount
      of contact time in which they participate. The data failed to show any strong
      connection between students' total workload and grades they received; rather,
      they showed some evidence that regular presence at contact hours was the most
      positive influence on grades. Less frequent presence at lectures tended to
      indicate less time spent on independent study. It was also found that pre
      clinical and clinical courses tended to require more work from students than
      other, more general subjects. While the present study does not provide conclusive
      evidence, it does indicate the need for further inquiry into the nature of the
      relationship between teaching and learning in higher education and for evaluation
      of the benefits (or otherwise) of more "self-directed" study.

PMID- 15510341
TI  - Developing a classification tool based on Bloom's taxonomy to assess the
      cognitive level of short essay questions.
AB  - The cognitive level of short essay questions taken from assessments of two
      veterinary courses at the Faculty of Veterinary Medicine of Utrecht University
      (FVMU) was evaluated using a simplified classification tool based on the taxonomy
      of Bloom. Classifications were made by teaching staff members (subject matter
      experts, or SME) and by faculty members not involved in teaching the course (non
      subject matter experts, or NSME). To compare the cognitive level assigned by
      raters in the SME group to that assigned by the NSME group, each test item was
      assigned a modal taxonomic level. The results indicate that the agreement level
      between a pair of raters within a group (SME or NSME) differed (34% to 77% and
      linear weighted Cohen's kappa coefficient 0.12 to 0.60). The agreement level on
      the modal taxonomic level between the SME and NSME groups for the two courses was
      65% and 73%, with a linear weighted Cohen's kappa coefficient of 0.43 and 0.63
      respectively. The requirement of expertise of a subject for classification is
      discussed. The introduction of the classification tool had a positive effect on
      teaching staff members' awareness of the importance of the cognitive level of
      assessments. Improvements to the classification tool to obtain higher agreement
      levels are proposed.

PMID- 15510342
TI  - Becoming an effective teacher: applied principles of adult learning.

PMID- 15510343
TI  - Hospital management principles applicable to the veterinary teaching hospital.
AB  - The Skills, Knowledge, Aptitude, and Attitude (SKA) Subcommittee of the National
      Commission on Veterinary Economic Issues (NCVEI) has identified the need for
      veterinary teaching hospitals (VTH) to be at the forefront of progressive
      business management to serve as a model for both students and practitioners to
      emulate. To provide a foundation for developing a model, this study reviewed
      pertinent literature applicable to the management of a VTH. Much of the
      literature relevant to VTH management relates to work completed for the human
      side of medicine (academic health centers, or AHCs) or to the private sector.
      This review explores management practices in strategic planning, financial
      management, human resource management, marketing, pricing, operations, and legal
      issues. It is concluded that strategic management is important to provide the
      foundation for success in the VTH. In addition, periodic financial reports are
      recommended, as are the development and use of benchmarks for financial
      management. Establishing positive, motivating human resource practices is also
      suggested, along with development of a marketing plan based on a clear
      understanding of VTH core competencies and the market's specific needs.

PMID- 15510344
TI  - Evaluating the curriculum of the veterinary school of Firat University, Turkey,
      in terms of professional and technical skills.
AB  - A significant portion of the problems faced by veterinarians is related to
      communication. These problems are intensely experienced between veterinary
      practitioners and animal owners; yet no lectures or courses aiming to improve
      professional skills are available in the curriculum of veterinary schools in
      Turkey. In this study, all students currently enrolled at, and 1992 and 1998
      graduates of, the Veterinary School of Firat University (VSFU), Turkey, were
      surveyed to evaluate the attitudes of veterinary students and graduates toward
      technical and professional skills. Data were collected from 581 students and 61
      recent graduates via personal interviews with students and questionnaires mailed
      to graduates; information was obtained about participants' technical and
      professional skills. The overall response rate was 85%. The results show that
      learning about technical and professional skills is highly valued; competence and
      comfort in skill sets are associated with comfort in establishing communication
      with instructors. Positive correlations were also noted between feeling
      comfortable with and feeling competent in both skill sets. In conclusion, it
      appears to be essential to introduce courses addressing improvement of
      professional skills to the curriculum of veterinary schools in Turkey, given that
      a successful veterinarian profile requires feeling competent in and comfortable
      with both technical and professional skills.

PMID- 15510345
TI  - Residency selection perceptions held by diplomates of the American College of
      Veterinary Ophthalmologists and veterinary ophthalmology residency applicant
      data.
AB  - Diplomates from the American College of Veterinary Ophthalmologists (DACVOs) who
      do not select residents concur with DACVOs involved in the selection of residents
      that it is a subjective process. Both groups believe that residents are selected
      on the basis of their perceived intelligence, hardworking attitude, and effective
      communication skills, along with the impression that the resident will fit well
      into a particular work environment. Survey data from successful veterinary
      ophthalmology resident applicants identify several helpful criteria. Applicants
      should have demonstrated academic achievement, including publication or
      presentation of information. Achievement of an advanced degree was helpful in
      obtaining a program. Although interviews may not be required for application to a
      program, they are extremely helpful in obtaining a position. Excellent
      communication skills are an asset.

PMID- 15510346
TI  - Learning basic science alongside veterinary students: creating an interactive
      classroom.
AB  - Dr. Scott Brown's dedication and contribution to the instructional programs of
      the University of Georgia College of Veterinary Medicine have been exceptionally
      meritorious. In the last eight years, he has served with the leadership among
      faculty in the design and approval of a new curriculum, and as chair of the
      curriculum committee he led the College in its implementation. Throughout this
      period his research productivity, mentorship of professional and graduate
      students, and professional development continued. Dr. Brown instills energy,
      broadens learning experiences from personal and professional development to basic
      science, and, in all probability, provides positive, life-changing experiences
      for his students. I am very pleased that he was recognized in 2003 with the Carl
      J. Norden National Distinguished Teacher Award.

PMID- 15510347
TI  - [Psychosomatic medicine and psychotherapy in Austria].
AB  - In present-day Austria, psychosomatic medicine and psychotherapy enjoy
      significantly more sociopolitical and cultural recognition perhaps as a heritage
      from the days of the Austrian monarchy -- than is reflected in their real
      presence. This development can be traced back to prewar times and the repudiation
      of the destructive national socialistic ideology. There is an immanent conflict
      between specialization in psychosomatic medicine and psychotherapy as an
      independent field of medicine and the integration of a psychosomatic basic
      approach into the general fields of medicine. The organization of psychotherapy
      is doubly anchored in the laws governing medical practice (PSY diploma) and the
      statutes governing the practice of psychotherapy; this, however, has not resolved
      the sensitive and only partially creative tension between the two. Austrian
      medical health politics are currently characterized by renewed efforts to
      organize the field of psychosomatic medicine. Should medical psychology and
      psychotherapy, internal medicine, psychiatry or general medicine provide the
      foundations for this new organization? This conflict is crucial since it will
      influence the further development of the entire medical field.

PMID- 15510348
TI  - [The phenomenology and psychodynamics of affects in borderline patients].
AB  - This paper presents a review of the phenomenology and psychodynamics of affects
      in borderline patients. The first part demonstrates that in most current
      conceptions of the borderline disorder affective disturbances are regarded as to
      be characteristic. In this context, the strong overlap between borderline
      disorders and affective disorders found in many empirical studies is described
      and different hypotheses are presented to explain this phenomenon. The second
      part of this review is concerned with the psychodynamics of affects in borderline
      patients. The role of affects in thinking, behaviour, self perception and the
      regulation of object relations is discussed. Borderline and other severe
      personality disorders are assessed from the perspective of affective
      disturbances. The psychodynamic functions of particularly characteristic affects
      such as anger, anxiety, depression and boredom are discussed. The close
      connection between affective and cognitive functioning in borderline patients is
      described and evaluated with regard to modern theories of affect and cognition.
      Finally, the role of affects in the treatment of borderline patients is
      discussed.

PMID- 15510349
TI  - [Assessment of the depersonalization-derealization syndrome using the German
      version of the Dissociative Experiences Scale].
AB  - OBJECTIVES: The goal of this study is to investigate the applicability of the
      German adaptation of the Dissociative Experiences Scale, the "Fragebogen zu
      dissoziativen Symptomen (FDS)", for research on depersonalization (DP) and
      derealization (DR), and to elucidate the phenomenology of DP / DR. METHODS: 101
      consecutively recruited inpatients were diagnosed with the German version of the
      Structured Clinical Interview for DSM-IV Dissociative Disorders for
      depersonalization/derealization. Furthermore, the FDS and the SCL-90-R were
      administered. RESULTS: 47 of 101 Patients were diagnosed with pathological DP /
      DR. The mean score of the DES scale of the FDS was 32.00 +/- 15.52. A cut-off
      score of 17.5 for the DES scale of the FDS yielded a 83.0 % sensitivity and 77.8
      % specificity. Depressive disorders, anxiety disorders and trauma-associated
      disorders were the most common comorbidity. CONCLUSIONS: The findings are
      comparable to the Anglo-American samples. The FDS was found to be quite effective
      for screening of DP / DR. The three-factor solution of the FDS was not well
      supported in this sample.

PMID- 15510350
TI  - [Quantitative and qualitative analyses in patients with environmentally related
      disorders].
AB  - BACKGROUND: Diagnostics and therapy of environmentally related disorders are
      hampered by one-sided assumptions and by discrepancies between therapists' and
      patients' assessments of the disease cause. OBJECTIVES: Discrepancies between
      patient and expert opinions are examined as to (1) whether the sample can be
      classified in subgroups according to the convergence or divergence between self
      and expert rating, (2) which features and (3) which disorder-related behaviour
      and concepts characterize these groups. METHODS: Medical, psychopathological and
      environmental symptoms were assessed and their relative influence evaluated. Four
      subgroups were defined by differentiating between high and low psychological
      stress according to self and expert judgment, and then compared using statistical
      and qualitative methods. RESULTS: 61 patients were assessed and assigned to four
      different subgroups according to the number of psychiatric diagnoses,
      psychological conflicts, personality structure, environmental exposure and
      psychosocial integration. CONCLUSIONS: Diagnostics of environmentally related
      disorders must be based on interdisciplinary tools. Treatment should incorporate
      the individual patient's conception of his or her disorder.

PMID- 15510352
TI  - The relentless pursuit of perfection in a machine bureaucracy: its impact on the
      practice of oral and maxillofacial surgery.

PMID- 15510351
TI  - [Comorbidity of mental disorders in the German G-DRG system -- effect on length
      of stay and revenue at a university hospital].
AB  - OBJECTIVES: The effect of comorbid mental disorders on the length of stay and
      revenue in a DRG system was investigated. METHODS: For 33,189 cases of an
      university hospital (year 2002) the revenue based on a fictitious base rate was
      calculated, at first with and then without inclusion of diagnosed comorbid mental
      disorders. Furthermore, the effect of the latter on the length of stay was
      examined. RESULTS: Renunciation of diagnoses of mental disorders lead to an
      different DRG grouping in 7.9 % of cases and to a reduction in revenues of about
      170.000. Minimal influence of comorbid mental disorders on the length of stay (R2
      = 0.02) could be detected for single diagnostic groups. CONCLUSIONS: The lacking
      influence of comorbid mental disorders on the length of stay in a university
      hospital is mainly determined by the limited period of inpatient treatment and by
      the low frequency of diagnosed mental disorders. Therefore, a psychosocial
      consultation-liaison service is of major importance to guarantee the diagnosis
      and treatment of a comorbid mental (process quality) disorder and to guarantee
      adequate revenues in the G-DRG system (quality of structure).

PMID- 15510353
TI  - Evaluation of facial soft tissue changes with optical surface scan after surgical
      correction of Class III deformities.
AB  - PURPOSE: To evaluate the soft tissue changes after correction of Class III
      dentoskeletal deformity with orthognathic surgery using the optical surface
      scanner as a 3-dimensional imaging tool and thin-plate splines as a morphometric
      analysis. PATIENTS AND METHODS: Forty-six patients with Class III dentoskeletal
      relationship who underwent a bimaxillary orthognathic surgical procedure
      involving advancement of the maxilla and mandibular setback to correct the
      deformity and create a Class I dentoskeletal relationship were included. Optical
      surface scans (lasergraphs) were obtained from all patients preoperatively and 6
      months postoperatively. They were evaluated for the soft tissue changes 3
      dimensionally and on the profile line. The cephalographs taken pre- and
      postoperatively were digitized and evaluated using the CogSoft digitizing
      software (Consultant Orthodontists Group Software, Bristol, United Kingdom) to
      confirm whether the preoperative surgical plan was applied. RESULTS: The soft
      tissue change in different areas of the face ranged from 30% on the nasal tip to
      80% on subnasale and from 50% on subcomissural region corresponding to lateral
      parts of the mandibular body to 100% on the pogonion. The direction of soft
      tissue movement was not solely forwards and backwards on a horizontal plane but
      had upward and downward vectors. CONCLUSIONS: The soft tissue changes following
      orthognathic surgery depend on various factors; hence it can be difficult to
      predict. However, there is a general trend as discussed in this study for the
      direction and amounts of facial soft tissue changes in the middle and lower
      facial thirds.

PMID- 15510354
TI  - Posttraumatic trigeminal nerve impairment: a prospective analysis of recovery
      patterns in a series of 103 consecutive facial fractures.
AB  - PURPOSE: To report the incidence of peripheral trigeminal nerve posttraumatic
      impairments and to compare different recovery patterns as observed in
      consideration of different fracture-related variables within 12-month follow-up.
      PATIENTS AND METHODS: Ninety-seven consecutive patients with 103 facial fractures
      were included involving emergence areas of supraorbital nerve, infraorbital
      nerve, or the region between the mandibular and mental foramina. Presurgical and
      postsurgical clinical neurosensory testing sessions were performed in each
      patient. Results of these assessments were compared within fracture
      characteristics and different sites of trauma. Statistical analysis (chi-square
      test) was performed on clinical observations. RESULTS: The incidence of
      trigeminal nerve impairments was 70.9% (54.4% in nondisplaced fractures, 88.2% in
      dislocated fractures, 100% in fractures with a direct nerve injury). Severe
      impairment was found in direct nerve injures and in many dislocated fractures.
      Mean recovery time was smaller in nondisplaced fractures than in dislocated
      fractures. Considering fracture site, the highest incidence of initial trigeminal
      nerve impairment was found in midfacial nondisplaced fractures. Midfacial
      fractures had better prognosis than mandibular fractures, and best prognosis was
      encountered in nondisplaced midfacial fractures. Residual hypoesthesia persisted
      in 11 sides with direct nerve injury after 12 months and involved tactile and
      discriminative sensibilities. CONCLUSION: Recovery patterns of posttraumatic
      trigeminal dysfunction are related to site and type of fracture; intraoperative
      assessment of involvement of nerve bundles within fracture rimes was associated
      with an incomplete recovery at the 12th month. Impairment of temperature and
      nociception are highly related to a direct nerve injury.

PMID- 15510355
TI  - Orofacial non-Hodgkins lymphoma in Nigerians.
AB  - PURPOSE: In this study, we sought to determine the occurrence of primary non
      Hodgkins lymphoma (NHL) in the oral and maxillofacial region among Nigerians.
      PATIENTS AND METHODS: We retrospectively studied hospital records that included
      radiographs of all patients with a histopathologically confirmed diagnosis of NHL
      in the Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria, between
      January 1992 and December 1997. Data were expressed as mean +/- SD or number (%).
      RESULTS: During the study period, 66 cases of NHL were recorded. Seventeen
      patients had concomitant extranodal lymphomas involving the gastrointestinal
      tract, nasopharynx, skin, lungs, kidney, and thyroid, in descending order. Three
      patients (4.5%) presented primarily with extranodal oral and maxillofacial
      disease. The ages of these patients ranged from 18 to 50 years (mean +/- SD, 32.3
      +/- 16.3 years; median, 29 years). Within the same period, there were 121 cases
      of Burkitts lymphoma. The onset of lesions varied from 6 to 20 weeks. Two
      patients had intermediate-grade lesions; the remainder had low-grade lesions. Two
      presented with stage II disease, and the remainder were stage I. All of the
      patients had chemotherapy with remission of their lesions but were followed up to
      6 months. Most of them did not complete the treatment cycles due to financial and
      social constraints. CONCLUSIONS: The rarity of primary NHL of oral and
      maxillofacial region has been aptly shown in this study. The need for the
      establishment of an effective oncology policy with the active collaboration of
      voluntary agencies is emphasized. This would ensure ready availability of the
      required chemotherapeutic agents and hospital care at affordable costs.

PMID- 15510356
TI  - Complications of laser-assisted uvulopalatopharyngoplasty (LA-UPPP) and
      radiofrequency treatments of snoring and chronic nasal congestion: a 10-year
      review of 5,600 patients.
AB  - PURPOSE: Recent laser and radiofrequency techniques for the treatment of snoring
      have provided improvements, but intraoperative and postoperative risks,
      complications, and long-term results have not been explored in a statistically
      large enough sample of patients. The goal of this article is to provide
      practitioners with important data and guidelines to help them in decision-making
      and prepare them to anticipate problems and recommend a systematic approach to
      avoid or treat complications. PATIENTS AND METHODS: This investigation was a
      retrospective review of 5,600 cases, performed over a 10-year period by a single
      investigator, in a private practice setting. The data on complications were
      gathered from chart review as well as questionnaires filled out on each patient
      and by patient reports. The inclusion criteria for this review were: 1) patients
      with a history of chronic snoring or nasal congestion; 2) patients with an
      American Society of Anesthesiologists physical status classification (ASA)
      Classes I or II medical history; 3) patients provide a detailed preoperative
      snoring questionnaires; 4) patients provide informed consent; 5) patients were
      followed for a minimum of 2 years following surgery; 6) patients completed a
      comprehensive postoperative survey; 7) operative report stating the exact nature
      of any complications; 8) surgeons provided a clinical assessment; 9) sleep apnea
      reports if available; and 10) patient body mass index of less than 30 kg/m2.
      RESULTS: Laser-assisted uvulopalatopharyngoplasty (LA-UPPP) was used for the
      treatment of snoring and mild obstructive sleep apnea in all cases; 40% of
      patients also had simultaneous nasal radioablation. No fatalities were recorded
      and fewer than 3% of patients had long-term complications. The most common
      intraoperative complication was bleeding, which occurred in 9.5% of patients.
      CONCLUSION: Reducing the amount of tissue resected from the soft palate helped
      reduce or eliminate the common complications of traditional
      uvulopalatopharyngoplasty procedures. LA-UPPP and radioablation procedures are
      effective, safe, and can be carried out in an office setting equipped with
      anesthesia monitors and services. The complications associated with the procedure
      were rare and usually manageable.

PMID- 15510357
TI  - Risk factors for third molar extraction difficulty.
AB  - PURPOSE: The purpose of this study was to measure the difficulty of third molar
      (M3) extractions and to identify demographic, anatomic, and operative variables
      associated with extraction difficulty. MATERIALS AND METHODS: To address the
      research purpose, we implemented a prospective cohort study and enrolled a sample
      composed of patients presenting for M3 removal. Predictor variables were
      categorized as demographic, anatomic, and operative. The primary outcome variable
      was difficulty of extraction, measured as extraction time per tooth. The
      secondary outcome variable was the surgeons postoperative estimate of M3
      extraction difficulty, measured on a 100-mm visual analog scale (VAS).
      Appropriate univariate, bivariate, and multivariate statistics were computed.
      RESULTS: The sample was composed of 82 subjects, having 250 M3s (53.2%
      mandibular) extracted, with a mean age of 26.2 +/- 10.7 years; 57.3% were female,
      72.0% were white. The mean operating time per M3 extraction was 6.9 +/- 7.6
      minutes. The mean estimate of difficulty was 39.6 +/- 24.7 mm and was
      significantly correlated (r = 0.68) with extraction time (P < .01). Surgical
      experience, M3 location (maxillary versus mandibular), procedure type, tooth
      position, number of teeth extracted, and tooth morphology were statistically
      associated (P < or = .05) with extraction time in a multivariate model.
      CONCLUSION: Our model indicates that the difficulty of M3 extractions is governed
      primarily by anatomic and operative factors with minimal influence from
      demographic factors.

PMID- 15510358
TI  - Modeling facial movement: I. A dynamic analysis of differences based on skeletal
      characteristics.
AB  - PURPOSE: To introduce a novel approach to analyze and model facial movements; and
      to quantify variations in facial movement caused by the extent of skeletal
      differences between the maxilla and mandible and the middle to lower facial
      heights. The hypothesis was that there are differences in facial movement related
      to the underlying facial skeleton which may be explained by the shape of the face
      rather than the pattern of movement. PATIENTS AND METHODS: The study sample
      consisted of 43 subjects (23 men, 20 women) with a mean age of 18.5 years (SD =
      11.90). Measures of the facial skeletal differences were made from lateral
      cephalometric radiographs, and subjects were classified as Class I and Class II,
      and normal to decreased lower anterior face height, respectively. Facial
      movements were recorded by a video-based tracking system. Descriptive and
      inferential statistics were performed on principal component scores generated
      from the movement data. A linear mixed-effects model was used to test for
      significant differences in movement among the different skeletal types. RESULTS:
      A dynamic modeling of facial movements was described that has numerous potential
      clinical applications. Also, differences in movement were found during the lip
      purse movement. Specifically, skeletal Class I individuals showed greater forward
      and upward movement during lip purse compared with individuals with severe
      skeletal Class II who moved their lips straight forward with less magnitude of
      movement. CONCLUSION: For most of the movements, apart from the lip purse,
      differences in motion were explained by static facial shape.

PMID- 15510359
TI  - Modeling facial movement: II. A dynamic analysis of differences caused by
      orthognathic surgery.
AB  - PURPOSE: The purpose of this study was to determine the facial movement
      characteristics of patients who underwent orthognathic surgery. The specific aims
      were to determine the presurgery versus postsurgery differences in facial
      movements; to determine whether the presurgery facial movements were similar
      among patients with different dentofacial deformities; and to determine whether
      patients have a more similar post- than presurgery dentofacial morphology and
      soft tissue movement. The hypothesis was that there are differences between the
      pre- and postsurgery facial movements. PATIENTS AND METHODS: The sample consisted
      of 19 patients (11 women, 8 men) with a mean age of 20.6 years (SD +/- 8.34).
      Facial movement and lateral cephalometric data were collected at presurgery, and
      at 6 and 12 months postsurgery. Measures of the facial skeletal differences were
      made from lateral cephalometric radiographs and facial movements were recorded by
      a video-based tracking system. Descriptive and inferential statistics were
      performed on principal component scores generated from the movement data. A
      linear mixed-effects model was used to test for significant differences in
      movement. RESULTS: Differences were found between the presurgery and 12-month
      postsurgery visits for the instructed smile, lip purse, eye closure, grimace, and
      mouth opening movements as well as the natural smile. Also, there were
      significant differences at presurgery among the dentofacial groups for the lip
      purse movement but no differences were found at postsurgery for any of the
      movements. CONCLUSION: These findings suggest that facial movements are effected
      by skeletal malocclusion and orthognathic surgical procedures.

PMID- 15510360
TI  - Postoperative imaging of zygomaticomaxillary complex fractures using digital
      volume tomography.
AB  - PURPOSE: Three-dimensional imaging using digital volume tomography after
      reduction of zygomaticomaxillary complex fractures was performed and evaluated.
      PATIENTS AND METHODS: Ten patients admitted for surgical treatment of
      zygomaticomaxillary complex fractures were included in the study. All patients
      were male, aged 17 to 81 years (average, 43.8 years). Preoperative diagnostics
      and surgical treatment involving open reduction under general anesthesia were
      performed as usual. One to 3 days (average, 1.6 days) postoperatively, a digital
      volume tomography data set was generated using the NewTom 9000 (NIM s.r.l.,
      Verona, Italy). After DICOM-import in eFilm Workstation 1.8.3 (Merge Technologies
      Inc, Milwaukee, WI), axial, coronal, and sagittal reconstructions were evaluated
      by 6 examiners with the help of 5 defined criteria. RESULTS: One data set was
      sufficient to visualize all fracture sites of the midface in all patients.
      Postprocessing using eFilm was successfully performed in all cases. Best scoring
      results were found regarding bony anchorage of screws and fitting of plates.
      Remarkable was the low level of metal artifacts in primary and secondary
      reconstructions, even in close proximity of the material. Most difficulty was
      encountered during the identification of the medial orbital wall, especially next
      to poorly ventilated ethmoidal cells. Osseous structures of older patients with
      decreased bone density proved difficult to visualize. CONCLUSION: Digital volume
      tomography using the NewTom 9000 is suitable for assessment of postoperative
      results after zygomaticomaxillary complex reduction.

PMID- 15510361
TI  - A prospective randomized clinical trial comparing 2.0-mm locking plates to 2.0-mm
      standard plates in treatment of mandible fractures.
AB  - PURPOSE: The purpose of this study was to compare standard 2.0-mm monocortical
      plates to 2.0-mm locking plates in the treatment of mandible fractures. PATIENTS
      AND METHODS: A prospective randomized clinical trial was conducted at Harborview
      Medical Center in Seattle, WA, from January 1, 2002, to February 1, 2003, to
      compare 2.0-mm locking plates to 2.0-mm standard plates in treating consecutive
      mandible fractures. Patients were randomly assigned to receive locking 2.0-mm
      plates (group A) or nonlocking 2.0-mm plates (group B). Complications were
      divided into major and minor categories. Each complication was analyzed according
      to which plate was used and where the fracture occurred. The number of days from
      injury to operation, average age, gender, American Society of Anesthesiologists
      (ASA) classification,compliance, and social habits were all reviewed. RESULTS:
      Ninety patients with 122 fractures met the inclusion criteria. Sixty-four
      fracture sites were treated with locking plates and 58 with standard plates. A
      total of 6 complications occurred: 2 occurred at the angle, 3 at the
      parasymphysis, and 1 at the body. Three complications occurred in the locking
      group and 3 in the standard group with complication rates equaling 4.6% and 5.2%,
      respectively. When comparing the overall complication rates according to plates
      used, the Fisher exact test showed no statistically significant difference
      between the locking and standard plates (P = .90). The 95% confidence interval
      for the odds ratio is from 0.1 to 7. CONCLUSION: Mandible fractures treated with
      2.0-mm locking plates and standard 2.0-mm plates present similar short-term
      complication rates.

PMID- 15510362
TI  - Using resorbable screws for fixation of cortical onlay bone grafts: an in vivo
      study in rabbits.
AB  - PURPOSE: The purpose of this study is to test bioresorbable screws as an
      alternative to titanium screw graft fixation. When cortical onlay grafts are
      used, it is necessary to rigidly immobilize them with titanium screws into the
      recipient site. The screws must be removed before placing implants into this
      site. Bioresorbable screws may be an alternative to titanium fixation,
      eliminating the additional morbidity associated with this. MATERIALS AND METHODS:
      Fifteen New Zealand White rabbits were divided into 3 groups. Bilateral tibial
      onlay bone grafts were placed in the mandible and secured using titanium
      fixation, bioresorbable fixation, or no fixation. After 6 weeks, all grafted
      sites were harvested. Hematoxylin-eosin and Giemsa staining were performed to
      evaluate inflammation, graft integration, and thickness. RESULTS: The treatment
      groups showed evidence of consolidation under light microscopy. Smooth
      integration of the graft borders with the recipient bone was identified. No
      integration was seen in the control group. The average thickness of the grafted
      sites was: 1) bioresorbable, 2.28 mm; 2) titanium, 1.87 mm; and 3) control, 1.06
      mm. The differences were statistically significant (P = .0004) between the
      titanium group and the control group, as well as between the bioresorbable and
      the control group (P = .01). There was no statistically significant difference
      between the 2 treatment groups (P = .19). CONCLUSION: The overall thickness of
      the treatment specimens was greater than that of the control group. The
      bioresorbable group showed graft integration equal to that of the titanium group,
      making it an adequate alternative for graft fixation.

PMID- 15510363
TI  - A modified method for preparing platelet-rich plasma: an experimental study.
AB  - PURPOSE: In this study, our aim was to prepare low-cost autogenous platelet-rich
      plasma (PRP) for use in minor bone grafting procedures. This was the preliminary
      study of an experimental study concerning augmentation of bony defects with a
      mixture of PRP and beta-tricalcium phosphate. MATERIALS AND METHODS: Venous blood
      was collected from marginal ear veins of New Zealand White rabbits in EDTA (K3)
      vacutainer tubes. Blood samples were divided into 2 groups, and PRP was prepared
      through 2 methods, 1 of which is a variant of the other. The 2 PRP preparation
      methods described in this study were modified from Landesberg et al (J Oral
      Maxillofac Surg 58:297, 2000) after several trials, because the platelet
      enrichment percentages we obtained using their method were very low. Complete
      blood counts of venous blood samples, PRP, and platelet poor plasma (PPP) were
      made. Statistical analyses were performed using SPSS for Windows (SPSS, Chicago,
      IL). RESULTS: It took approximately 30 minutes to prepare PRP with both methods.
      Platelet counts in PRP were increased with respect to venous blood platelet
      counts. The differences between the experimental groups and genders were
      evaluated statistically with Mann-Whitney U tests (P < .05). Correlations between
      the groups and genders were also evaluated (P < .05). CONCLUSION: It was
      experimentally shown that PRP with high platelet counts can be prepared using
      this modified method without the need for costly autotransfusion systems.

PMID- 15510364
TI  - Horizontal alveolar distraction: a surgical technique with the transport segment
      pedicled to the mucoperiosteum.
AB  - PURPOSE: The study goal was to describe a surgical technique for performing
      horizontal alveolar distraction with the aim of increasing the width of alveolar
      ridges that are too narrow for dental implant placement. MATERIALS AND METHODS: A
      transport segment is cut from the vestibular side of the ridge, using osteotomes,
      and maintaining extensive attachment to the mucoperiosteum. The distraction screw
      is placed through the vestibular mucosa and the transport segment, in vestibular
      palatal direction. Distraction is then performed to increase ridge width.
      RESULTS: We successfully applied this technique in a patient who required 2
      dental implants at adjacent sites in the upper jaw but whose alveolar ridge was
      too narrow for direct implantation. With horizontal distraction, ridge width was
      successfully increased, allowing placement of the 2 implants (diameter, 3.3 and
      4.1 mm). CONCLUSION: This technique shows promise for patients requiring implants
      in a narrow alveolar ridge. Depending on each patients specific requirements, we
      suggest that it be taken into account as a possible alternative to existing
      techniques.

PMID- 15510365
TI  - Surrogate markers of health after titanium dental implant placement.
AB  - PURPOSE: We investigated the effects of dental implants on patient health, as
      measured by commonly used surrogates of human homeostasis, including hepatic
      metabolic and synthetic ability, renal regulatory functions, bone turnover,
      clotting, infection, and inflammation. MATERIALS AND METHODS: Patients enrolled
      had 1 to 3 mandibular uncoated, endosseous titanium dental implants placed and
      restored. Patients were evaluated serially over 6 months. Blood and urine tests
      were collected immediately before and 6 months after implant placement. Paired
      student t tests were used to compare quantified laboratory values. Nonquantified
      values were evaluated using the McNamara chi square analysis to assess patterns
      of change. RESULTS: Thirty-one patients met the inclusion criteria. A total of 53
      dental implants were placed. Three values were found to be significantly
      different between the 2 time periods: total protein (P < .008), lactate
      dehydrogenase (P < .002), and hematocrit (P < .017). Total protein and lactate
      dehydrogenase were within the laboratory range of normal and judged to be
      clinically nonsignificant. On reevaluation, the significant change in hematocrit
      was entirely accounted for by a single outlier. This was attributed to laboratory
      error. CONCLUSION: No clinically significant effects on surrogate markers of
      health were found 6 months after placement of titanium dental implants. This
      series is the only one in the dental, craniomaxillofacial, and orthopedic
      literature showing a lack of adverse human health effects after dental implant
      placement, as measured by accepted surrogate measures of human homeostasis.

PMID- 15510366
TI  - Restoration of the edentulous maxilla: the case for the zygomatic implants.

PMID- 15510367
TI  - The case for bone graft reconstruction including sinus grafting and distraction
      osteogenesis for the atrophic edentulous maxilla.

PMID- 15510368
TI  - Aggressive angiomyxoma of the oral floor: report of a case.

PMID- 15510369
TI  - Isolated bilateral orbital floor fractures: a series of 3 cases.

PMID- 15510370
TI  - Inadvertent intracranial placement of a nasogastric tube in a patient with severe
      craniofacial trauma: a case report.

PMID- 15510371
TI  - Obstructive parotitis after rhytidectomy.

PMID- 15510372
TI  - A PCR based B-genome-specific marker in Brassica species.
AB  - Previous hybridisation studies showed that the repetitive DNA sequence pBNBH35
      from Brassica nigra (genome BB, 2n=16) bound specifically to the B-genome and not
      to the A- or C-genomes of Brassica species. We amplified a sub-fragment of
      pBNBH35 from B. nigra by PCR, cloned and sequenced this sub-fragment, and
      confirmed that it was a 329-bp sub-fragment of pBNBH35. PCR and hybridisation
      techniques were used to confirm that the pBNBH35 sub-fragment was Brassica B
      genome-specific. Fluorescence in situ hybridisation (FISH) in B. nigra, B. juncea
      (AABB, 2n=36) and B. napus (AACC, 2n=38) showed that the pBNBH35 sub-fragment was
      present on all eight Brassica B-genome chromosomes and absent from the A- and C
      genome chromosomes. The pBNBH35 repeat was localised to the centromeric region of
      each B-genome chromosome. FISH clearly distinguished the B-genome chromosomes
      from the A-genome chromosomes in the amphidiploid species B. juncea. This is the
      first known report of a B-genome repetitive marker that is present on all B
      genome chromosomes. It will be a useful tool for the detection of B chromosomes
      in interspecific hybrids and may prove useful for phylogenetic studies in
      Brassica species.

PMID- 15510374
TI  - Ending discrimination two years at a time.

PMID- 15510373
TI  - Characterisation of the serotonin efflux induced by cytosolic Ca2+ and Na+
      concentration increase in human platelets.
AB  - BACKGROUND/AIM: The present study aimed at elucidating the mechanism(s) of
      serotonin (5-HT) efflux induced by thapsigargin from human platelets in the
      absence of extra-cellular Ca2+. METHODS: Efflux of pre-loaded radiolabeled
      serotonin was generally determined by filtration techniques. Cytosolic
      concentrations of Ca2+, Na+ and H+ were measured with appropriate fluorescent
      probes. RESULTS: 5-HT efflux from control or reserpine-treated platelets--where
      reserpine prevents 5-HT transport into the dense granules--was proportional to
      thapsigargin evoked cytosolic [Ca2+]c increase. Accordingly factors as
      prostacyclin, aspirin and calyculin which reduced [Ca2+]c-increase also inhibited
      the 5-HT efflux. Thapsigargin, which also caused a remarkable increase in
      cytosolic [Na+]c, promoted less 5-HT release, in parallel to lower [Na+]c and
      [Ca2+]c increase, when added to platelet suspensions containing low [Na+]. The
      Na+/H+ exchanger monensin increased the [Na+]c and induced 5-HT efflux without
      affecting the Ca2+ level. The 5-HT efflux induced by both [Ca2+] or [Na+]c
      increase did not depend on pH or membrane potential changes, whereas it decreased
      in the absence of extra-cellular K+, and increased in the absence of Cl- or Na+.
      CONCLUSION: Increases in [Ca2+]c and [Na+]c independently induce serotonin efflux
      through the outward directed plasma membrane serotonin transporter SERT. This
      event might be physiologically important at the level of capillaries or narrowed
      arteries where platelets are subjected to high shear stress which causes [Ca2+]c
      increase followed by 5-HT release which might exert vasodilatation.

PMID- 15510375
TI  - Just for teens. Low-carb confusion.

PMID- 15510376
TI  - Health savings accounts. HSAs can help some save for medical expenses.

PMID- 15510377
TI  - Surprising effects of statins.

PMID- 15510378
TI  - The hottest diabetes research. Part 2.

PMID- 15510379
TI  - When meds don't mix. Taking multiple medications? Washing your pills down with
      grapefruit juice? Be careful--you may be headed for a drug interaction.

PMID- 15510380
TI  - Happy, healthy holidays. How to ditch your stress, boost your health, and enjoy
      yourself all through the season.

PMID- 15510382
TI  - Quick starts. Get your dinner party going with some microwave magic.

PMID- 15510381
TI  - What's for (Thanksgiving) dinner? No law says it has to be turkey.

PMID- 15510383
TI  - New twists on the side. Tweak your favorite recipes for a healthier holiday meal.

PMID- 15510384
TI  - Fabulous finales. Great tasting desserts come to those who wait.

PMID- 15510385
TI  - Type 2 prevention in seniors. Weight loss, exercise, or both? Research profile.
      Bret Goodpaster, PhD.

PMID- 15510386
TI  - Stroke and anemia in HIV/AIDS.

PMID- 15510387
TI  - Policy watch. How far should we look?

PMID- 15510388
TI  - Burnout: the health care worker as survivor.
AB  - Research has attempted to identify the unique stressors involved in HIV/AIDS
      care, and suggestions have been made to alleviate stress and burnout in HIV/AIDS
      health care workers. While the level of stress and burnout is not likely to be as
      high as in the pre-HAART era, health care workers are likely to provide better
      care to patients when they are satisfied with their work and suitably prepared to
      deal with emerging challenges.

PMID- 15510389
TI  - Editorial comment: the stresses on AIDS caregivers in the HAART era.

PMID- 15510390
TI  - Expanding role of conformulations in the treatment of HIV infection: impact of
      fixed-dose combinations.
AB  - Fixed-dose combination therapy is more convenient than combination therapy with
      the same drugs taken separately and can improve adherence. Improved adherence is
      often associated with enhanced outcomes, which, in turn, can reduce the cost of
      care. In addition, the lower costs of generic fixed-dose combinations in resource
      poor areas can extend treatment to larger numbers of patients who would otherwise
      have no access to antiretrovirals at all. In any setting, fixed-dose combinations
      reduce the number of pills, simplify the dosing regimen; are easier to take;
      ensure that the correct dosage of each component is taken; and are more cost
      effective.

PMID- 15510391
TI  - Editorial comment: fixed-dose combination formulations are the answer, what was
      the question?

PMID- 15510392
TI  - Anemia during treatment of hepatitis C in HIV-infected patients.
AB  - Anemia is a significant adverse effect of current hepatitis C treatment and may
      be a particular problem for HIV-infected patients, in whom there is a high
      prevalence of disease- or drug-related anemia at baseline. Hepatitis C treatment
      induced anemia in HIV-HCV-coinfected patients can lead to ribavirin dose
      reduction or premature discontinuation of hepatitis C therapy, limiting sustained
      virologic response rates. Mean decreases in hemoglobin levels during hepatitis C
      treatment appear to be less in HIV-HCV-coinfected patients than in HCV
      monoinfected patients, but any decrease in hemoglobin level may be more of a
      problem for coinfected patients. Thus, close monitoring of the hemoglobin level
      and appropriate management of the anemia that may develop in HIV-infected
      patients during hepatitis C therapy is essential.

PMID- 15510393
TI  - Editorial comment: erythropoietin for treatment-related anemia in persons with
      hepatitis C--questions remain.

PMID- 15510394
TI  - Oroesophageal candidiasis.

PMID- 15510395
TI  - Trichothecenes with a special focus on DON. Proceedings of a workshop. September
      10-12, 2003. Dublin Ireland.

PMID- 15510396
TI  - [The 44th annual meeting of the Japanese Society of Nuclear Medicine.  Kyoto,
      Japan. November 4-6, 2004. Program].

PMID- 15510397
TI  - [The 44th annual meeting of the Japanese Society of Nuclear Medicine.  Kyoto,
      Japan. November 4-6, 2004. Abstracts].

PMID- 15510398
TI  - [Regional meeting of the Japanese Society of Otolaryngology. Japan.  2003.
      Abstracts].

PMID- 15510399
TI  - [Epiphyseolysis capitis femoris].

PMID- 15510400
TI  - Rehabilitation for traumatic brain injury in children and adolescents.

PMID- 15510401
TI  - [The 39th conference of Japanese Medical Society of Alcohol and Drug Studies.
      September 9-11, 2004. Abstracts].

PMID- 15510402
TI  - [The 32nd annual meeting of the Japanese Society of Clinical Immunology. Tokyo,
      Japan. October 8-9, 2004. Abstracts].

PMID- 15510403
TI  - Global strategy: breastfeeding critical for child survival--UNICEF and WHO call
      for increased commitment to appropriate feeding practices for all infants and
      young children.

PMID- 15510405
TI  - Cadaver case puts focus on regents.

PMID- 15510404
TI  - Substance dependence treatable, says neuroscience expert report: psychosocial,
      environmental, biological and genetic factors all play significant roles in
      dependence, says new report published by WHO.

PMID- 15510406
TI  - [The EasyScope--an alternative to the conventional Macintosh Laryngoscope?
      Anesthesiology Intensive Emergency Medicine 2004; 29:3438-52].

PMID- 15510407
TI  - [Cattle and pig tapeworm].

PMID- 15510416
TI  - Abstracts from the meeting of the Hungarian Society of Microbiology. October 8
      10, 2002. Balatonfured, Hungary.

PMID- 15510417
TI  - Gender differences in memory for the appearance of others.
AB  - Five studies investigated gender differences in the accurate recall of the
      appearance of others. The greater interpersonal orientation and interpersonal
      sensitivity of women were predicted to give women an advantage over men in
      appearance accuracy. Under both directed- and incidental-learning conditions,
      women more accurately recalled information concerning the appearance of their
      social targets than did men, participants' memory for the appearance of female
      targets was more accurate than it was for male targets, and neither gender was
      found to be a relative advantage in recalling the appearance of same-gender
      targets. The motivational and knowledge-based factors that might underlie a
      gender difference in appearance accuracy are discussed.

PMID- 15510418
TI  - When to fire: anticipatory versus postevent reconstrual of uncontrollable events.
AB  - These studies examined the conditions under which people engage in anticipatory
      construal before an evaluative event versus reconstrual after the event. Computer
      software informed college students that there was a 1.5%, 12%, 88%, or 98.5%
      chance that an opposite-sex student would pick them for a hypothetical date. When
      people had extreme expectations (1.5% or 98.5%), they changed their view of the
      student to be consistent with their expectations before learning the outcome
      (anticipatory reconstrual). When people had moderate expectations (12% or 88%),
      they formed relatively unbiased impressions before hand but reconstrued after
      learning the outcome of the dating game (postevent reconstrual). Either strategy
      can ameliorate the pain of a negative event in ways that people do not
      anticipate. Forecasters predicted that loosing would make them feel worse than it
      did and selected a higher dose of a drug to cope with an anticipated loss than
      did people who actually lost.

PMID- 15510419
TI  - Combating car parking crime in the United Kingdom.

PMID- 15510420
TI  - Signs of age in today's workforce.

PMID- 15510422
TI  - Bibliography. Current World Literature. Cardiovascular system.

PMID- 15510421
TI  - Scientific meeting of the American Institute for Psychoanalysis. Disclosure, HIV,
      and the dialectic of sameness and difference.

PMID- 15510423
TI  - Bibliography. Current World Literature. Infectious diseases.

PMID- 15510424
TI  - Bibliography. Current World Literature. Critical care outcomes.

PMID- 15510425
TI  - Trends in health insurance coverage and access among black, Latino and white
      Americans, 2001-2003.
AB  - Overall health insurance rates changed little among nonelderly black, Latino and
      white Americans between 2001 and 2003, according to new findings from the Center
      for Studying Health System Change (HSC). But sources of coverage shifted-
      especially for Latinos--from employment-based insurance to public coverage,
      suggesting the economic downturn took a greater toll on Latinos. Low-income
      Latinos and whites were particularly hard hit by declines in employer coverage.
      Shifting sources of coverage had little effect on access to medical care. With
      the sole exception of decreased access to specialists among blacks, access to
      care did not change between 2001 and 2003. Significant gaps in access to care
      among Latinos, blacks and whites persisted, with Latinos and blacks consistently
      reporting lower levels of access than whites.

PMID- 15510426
TI  - The possible relationship between visual deficits and dyslexia.

PMID- 15510427
TI  - A critique of Mody, Studdert-Kennedy, and Brady's "Speech perception deficits in
      poor readers: auditory processing or phonological coding?".
AB  - A 1997 article by Mody, Studdert-Kennedy, and Brady claimed that their studies
      constituted a critical test of two hypotheses concerning students with reading
      impairment: (a) that they experience speech-specific failure in phonological
      representation, and (b) they display general deficits in auditory temporal
      processing. From these studies, the authors concluded that their findings were
      consistent with the first hypothesis but were not in agreement with the second. A
      critical analysis of the Mody et al. article leads to the conclusion that it
      makes no contribution to that debate because (a) the children in the Poor reading
      group did not meet the accepted reading-impairment criterion of being delayed by
      at least 1 year in their reading skills, (b) there were severe violations of
      statistical assumptions, and (c) their conclusions were based on the failure to
      find significant differences, thus compelling them to accept the null hypothesis
      as proven, in the absence of any statistical power analysis.

PMID- 15510428
TI  - Options and limitations of the cognitive psychological approach to the treatment
      of dyslexia.
AB  - If the field of cognitive psychology is to avoid the use of introspective
      methods, it must focus on the objective norms or rules for correct performance of
      cognitive tasks and not on subjective processes. In this manner, the cognitive
      approach will be more logical than empirical. Cognitive psychology alone is not
      able to answer the question "Why is it that some people have difficulty following
      some of the cognitive norms or rules?" Behaviorism and connectionism can make
      more important contributions here. In the treatment of dyslexia, emphasis must be
      placed on the fact that reading is a skill that requires both automatization and
      awareness. To have a flexible and functional combination of these, we must borrow
      from cognitive psychology, connectionism, and behaviorism.

PMID- 15510429
TI  - Foundation-level dyslexia: assessment and treatment.
AB  - It is supposed that there is an early, foundation stage in beginning reading
      during which children acquire basic letter-sound knowledge, a capability for
      alphabetic processing, and a logographic sight vocabulary. An assessment of
      foundation processes was administered to Scottish children with reading
      difficulties (n = 51) and to reading-level-matched controls (n = 56). The results
      suggested that the foundation is normally in place by the time a reading age of
      about 7 years has been achieved. Foundation-level dyslexia is identifiable in
      children with reading difficulty whose reading ages fall below this level.
      Differing patterns of dyslexia were observed, depending on whether the primary
      effect was on letter-sound learning (literal dyslexia), the acquisition of the
      alphabetic process (alphabetic dyslexia), or retention of a sight vocabulary
      (logographic dyslexia). Balanced dyslexia, in which both alphabetic and
      logographic functions were impaired, was also found. Some implications for
      assessment and treatment are discussed.

PMID- 15510430
TI  - Patterns of phonological and memory processing in beginning readers and spellers
      of Greek.
AB  - This study examined the patterns of reading and spelling performance of first
      grade Greek children who either were facing difficulties in literacy acquisition
      or were normal achievers. In addition, we studied the relationship between
      obtained literacy development levels and the children's phonological awareness
      and ability to retain phonological information in short-term memory. The
      participants were tested in the reading of single letters, letter clusters,
      words, and nonwords, as well as in word and nonword spelling. Furthermore, their
      phonological processing knowledge was assessed via a battery of phonological
      awareness tasks and short-term memory phonetic-representation tasks. The main
      findings of the study were as follows: (a) Accurate decoding of Greek was
      achieved by almost every young child (attributed mainly to the nature of the
      Greek writing system); (b) the time the children needed to process a written item
      was the crucial index of their difficulty in literacy acquisition; (c) spelling
      was performed by deriving the orthographic form of a word on the basis of sound
      spelling correspondence knowledge; (d) although the children with difficulties in
      literacy development had achieved a satisfactory performance in phonological
      processing, their performance was nevertheless significantly lower than that of
      the normal achievers; and (e) phonemic awareness and speech rate tasks were among
      the best predictors of learning to read and spell Greek words.

PMID- 15510431
TI  - Automatization aspects of dyslexia: speed limitations in word identification,
      sensitivity to increasing task demands, and orthographic compensation.
AB  - A study is presented in which three characteristics of dyslexia were examined:
      (a) speed limitations in word identification, (b) sensitivity to increasing task
      demands, and (c) orthographic compensation. Ten students with dyslexia (10 years
      old) were compared to 10 chronological-age controls and 20 reading-age controls
      on their performance in reading. Response latencies of the students with dyslexia
      were slower when familiar words, letter clusters, and nonwords had to be named. A
      larger word-frequency effect and a larger word-length effect in the these
      students indicates that they have difficulty with increasing task demands. In
      addition, a subword-frequency effect was found to be larger in the students with
      dyslexia. These differences among the three groups of students are interpreted in
      terms of automatization. Furthermore, it is suggested that students with dyslexia
      may have a preference for large orthographic units, which is used as a
      compensatory tool in reading.

PMID- 15510432
TI  - Kindergarten prevention of dyslexia: does training in phonological awareness work
      for everybody?
AB  - This study examined the effects of training in phonological awareness on
      kindergarten children. Comparisons of children at risk (i.e., children with
      initially low levels of metalinguistic ability) with initially average and
      advanced children revealed that training gains were similar for all of these
      groups. Furthermore, training had comparable long-term effects on reading and
      spelling in Grades 1 and 2 for each group. In fact, the trained children at risk
      showed better reading and spelling performance than a randomly selected control
      group. Although considerable individual differences in training effectiveness
      were found Within the group of at-risk children, there was clear evidence that
      the training program substantially reduced the risk of becoming dyslexic in
      school.

PMID- 15510433
TI  - Who benefits from training in linguistic awareness in the first grade, and what
      components show training effects?
AB  - Who among first graders benefit from training in linguistic awareness, and what
      components of the linguistic awareness are most amenable to training effects? At
      the beginning of Grade 1 prospective at-risk readers (26 out of 117) were
      identified on the basis of very low phonological awareness. In the autumn term,
      they received practice in linguistic awareness. When compared to controls
      individually matched controls on phonological awareness, listening comprehension,
      and WISC-R scores, the intervention group showed a more rapid building-up of
      phonological awareness, especially phoneme-blending ability, as well as
      superiority in word recognition, spelling, and listening comprehension, which
      were sustained until the end of Grade 1. Reading comprehension could not be
      compared because 8 of the 26 controls did not read fluently enough to be tested.
      The half of the control group with cognitive delays, receiving normal special
      education instruction, performed consistently worse than their matched pairs in
      the intervention group. The latter group showed development of phonological
      awareness, decoding, and spelling equal to that of the cognitively nearly average
      intervention group and their matched pairs in the control group, who received no
      additional support. These three groups, originally defined as at-risk readers,
      performed at the level of other preschool nonreaders at the end of Grade 1. In
      sum, the children with cognitive delays benefitted from training in linguistic
      awareness. The results underscore the importance of phoneme synthesis skills in
      beginning reading and spelling, at least with regular languages.

PMID- 15510434
TI  - Effects of outpatient treatment of dyslexia.
AB  - The effects of a Dutch intervention program for dyslexia are reported. The
      program was individually tailored, depending on the style of reading, the phase
      of the learning process, and the intermediate results of the treatment. Two
      groups of participants were involved: (a) a group of children with pure dyslexia
      (n = 109) and (b) a group that had reading problems but also suffered from
      cognitive deficits or psychiatric symptoms (n = 29). Scores of reading single
      words and text at intake and after the intervention were analyzed to assess the
      efficacy of the intervention program. Furthermore, the effects of pre
      intervention variables such as intelligence, reported speech, and language
      problems and of intervention variables such as the initial level of performance
      and the duration of the treatment were examined. Both groups benefitted from the
      intervention, but the children with pure dyslexia profited most. Neither of the
      groups could catch up the reading deficit. Intelligence and reported speech and
      language problems did not affect the treatment outcomes. Individual differences
      in treatment outcome were related to the absolute level of word reading and age
      at intake. In the group with comorbidity, the intervention program was more
      successful in relatively younger children. Within this group, the cognitive
      deficits and types of psychiatric problems were not related to the treatment.

PMID- 15510435
TI  - The development of phonological abilities and their relation to reading
      acquisition: case studies of six Finnish children.
AB  - The relation between phonological abilities and reading acquisition and the
      interindividual variation in the development of different phonological
      manipulation skills were assessed for six 7-year-old Finnish nonreaders.
      Intensive time series data were collected by following the children for 13
      months. Assessments were conducted every 4 weeks with five phonological
      manipulation tests. The results indicated gradual progress at the group level.
      However, analysis of the individual profiles indicated large interindividual
      variation in the rate of improvement and in the relation between different
      manipulation skills and reading acquisition.

PMID- 15510436
TI  - Early language development and kindergarten phonological awareness as predictors
      of reading problems: from 3 to 11 years of age.
AB  - At the end of Grade 4, 481 children on the Danish island of Bornholm were
      screened using group tests for sentence reading. For 205 of these children,
      language and speech data from the speech therapist's screening at age 3 were
      available, as well as language comprehension and linguistic awareness data from
      the kindergarten year (age 6) and word decoding measures in Grades 2 and 3. A
      path analysis revealed significant paths from early language abilities at age 3
      through expressive and receptive language in kindergarten via language awareness
      in kindergarten and word decoding in Grade 2 to sentence reading in Grades 3 and
      4. The subgroup of children with parents who had reported a history of reading
      problems at school entry scored significantly below average on sentence reading
      in Grade 4. The subgroup of children that were reported to show a very low
      interest in books and story reading before age 5 also scored low on sentence
      reading in Grade 4. Statistically significant but weak relationships were also
      found between parents' educational background, parents' library visits, and
      number of books at home and the child's reading ability in Grade 4.

PMID- 15510437
TI  - Reading and dual-task balancing: evidence against the automatization deficit
      explanation of developmental dyslexia.
AB  - Nicolson and Fawcett (1990) demonstrated specifically impaired balancing
      performance of children with dyslexia when balancing had to be done
      simultaneously with a secondary task. This finding was taken as evidence for a
      general automatization deficit of children with dyslexia. We attempted to
      replicate this finding with German children with dyslexia, whose characteristic
      reading difficulty is a fluency problem quite in correspondence with the
      automatization deficit explanation. Because we were concerned about a potential
      confound between dyslexia and attention-deficit/hyperactivity disorder (ADHD), we
      also collected teacher ratings on ADHD symptoms. We found that poor dual-task
      balancing was limited to children with higher ADHD ratings and that children with
      dyslexia without higher ADHD ratings performed as well on dual-task balancing as
      age-matched control children. This finding supports the aforementioned confound.
      Together with other findings from our research group, it supports the position
      that, even in consistent orthographies, difficulties in learning to read are
      caused by a specific phonological deficit.

PMID- 15510438
TI  - The LD label for relatively well-functioning students: a critical analysis.
AB  - The number of students identified since the mid-1970s as having learning
      disabilities has produced a corresponding increase in the population of such
      individuals in postsecondary programs. The Americans with Disabilities Act, along
      with Section 504 of the Vocational Rehabilitation Act of 1973, provide the basis
      for civil rights for students in higher education. These laws protect individuals
      who have a substantial limitation in a major life activity when compared with the
      general population. A disparity between the legal definition and the clinical
      definition of learning disabilities, which can encompass those identified on the
      basis of academic underachievement relative to intellectual potential, has
      stimulated debate about the fairest, most appropriate standard for declaring a
      student functionally impaired. Extending services to individuals without
      significant academic impairment may tax or even deplete scarce resources for
      others in greater needs, distort the normal processes by which individuals select
      careers, and diminish the credibility of the diagnosis itself.

PMID- 15510440
TI  - Reading research for students with LD: a meta-analysis of intervention outcomes.
AB  - The present article provides a meta-analysis of instructional research with
      samples of children and adolescents with learning disabilities in the domains of
      word recognition and reading comprehension. The results of the synthesis showed
      that a prototypical intervention study has an effect size (ES) of .59 for word
      recognition and .72 for reading comprehension. Four important findings emerged
      from the synthesis: (a) Effect sizes for measures of comprehension were higher
      when studies included derivatives of both cognitive and direct instruction,
      whereas effect sizes were higher for word recognition when studies included
      direct instruction; (b) effect sizes related to reading comprehension were more
      susceptible to methodological variation than studies of word recognition; (c) the
      magnitude of ES for word recognition studies was significantly related to samples
      defined by cutoff scores (IQ > 85 and reading < 25th percentile), whereas the
      magnitude of ES for reading comprehension studies was sensitive to discrepancies
      between IQ and reading when compared to competing definitional criteria; and (d)
      instructional components related to word segmentation did not enter significantly
      into a weighted least square hierarchical regression analysis for predicting ES
      estimates of word recognition beyond an instructional core model, whereas small
      group interactive instruction and strategy cuing contributed significant variance
      beyond a core model to ES estimates of reading comprehension. Implications
      related to definition and instructional components that optimize the magnitude of
      outcomes are discussed.

PMID- 15510439
TI  - Early intervention for reading disabilities: teaching the alphabet principle in a
      connectionist framework.
AB  - Forty-eight children referred by teachers at the end of first grade for
      difficulty in reading were randomly assigned to three treatments, all of which
      modeled connections between written and spoken words but did not teach phonics
      rules, for eight half-hour individual tutoring sessions. The children were taught
      48 words of varying orders of spelling-sound predictability (Venezky, 1995) using
      a whole-word method, for making connections between a word's name and its
      constituent letters; a subword method, for making connections between each color
      coded spelling unit and its corresponding phonemes; or a combined whole-word and
      subword method. Regardless of the method used, children improved reliably on
      standardized reading measures and the taught words, showing that they could make
      connections between written and spoken words at the whole word and subword
      levels, even when rules were not taught. By posttest, the subword method showed a
      reliable advantage on a standardized test of real word reading. Knowledge of
      sounds associated with both multiletter and single-letter spelling units
      predicted reading achievement. Order of spelling-sound predictability (easy,
      moderate, difficult) was correlated with standardized measures of reading at
      pretest and posttest, and the magnitude of the relationship increased as a result
      of the intervention. Individual differences in verbal intelligence, rapid
      automatized naming, and phonological and orthographic skills predicted response
      to the intervention. Instructional implications of the results are discussed.

PMID- 15510441
TI  - Occupational and educational aspirations and attainment of young adults with and
      without LD 2 years after high school completion.
AB  - A national longitudinal database was used to compare the aspirations and
      attainment of individuals with and without learning disabilities (LD) 2 years
      after high school completion. Analyses revealed that individuals with LD reported
      lower graduation rates, were more likely to aspire to moderate- (men) or low
      prestige (women) occupations, and were more likely to be employed and less likely
      to be enrolled in some type of postsecondary education program than their
      nondisabled peers. High educational aspirations in Grade 12 and successful
      completion of an academic or college-prep high school program were equally
      important in predicting 2-year postsecondary status for adolescents enrolled in
      postsecondary education regardless of disability status. However, depending on
      disability status, different predictors were identified for individuals who were
      either employed or out of the workforce. These results point to a continued need
      for transition planning and support for young adults with LD and suggest ways in
      which professionals can anticipate and adjust for identified differences in
      aspirations and postsecondary attainment.

PMID- 15510442
TI  - Comparison of students classified as LD who petitioned for or fulfilled the
      college foreign language requirement.
AB  - In this study, we compared the cognitive, academic achievement, and demographic
      profiles of 46 students from one university who had been classified as learning
      disabled (LD) and had received permission to substitute courses for the
      university's foreign language (FL) requirement (petition group) with the profiles
      of 21 students from the same university who had been classified as LD and had
      fulfilled the university's FL requirement by passing FL courses (nonpetition
      group). Results showed no significant differences between the two groups on
      measures of reading, mathematics, written language, American College Testing
      score, and graduating grade point average when IQ was used as a covariate. More
      petition than nonpetition students had at least a 1.0 SD discrepancy between IQ
      and achievement and had been referred only for FL learning problems. More
      nonpetition than petition students had taken an FL in college and received
      accommodations in the FL. The two groups together appeared to constitute a
      heterogeneous group of learners, with more than half failing to meet a minimum
      discrepancy criterion for classification as LD. The discussion addresses the
      classification system for LD, the process for determining the presence of FL
      learning problems and how to address them, and directions for further research.

PMID- 15510443
TI  - Students classified as LD and the college foreign language requirement: a
      quantitative analysis.
AB  - This study was conducted to determine whether students classified as learning
      disabled (LD) who were permitted to substitute courses for the college foreign
      language (FL) requirement at one university would display significant cognitive
      and academic achievement differences when grouped by level of discrepancy between
      IQ and achievement, by discrepancy between achievement according to different
      measures, and by level of performance on phonological-orthographic processing
      measures, on the Modern Language Aptitude Test (MLAT), and in FL courses. Results
      showed that there were no differences among students with different levels of
      discrepancy (i.e., < 1.0 SD, 1.0-1.49 SD, and > 1.50 SD) on MLAT and American
      College Testing (ACT) scores, graduating grade point average (GPA) or college FL
      GPA. Results also showed that among students who scored below versus at or above
      the 25th percentile on phonological-orthographic processing measures, there were
      no differences on measures of IQ, ACT, MLAT, and GPA, as well as most measures of
      academic achievement. Implications for the use of the LD label to grant FL course
      substitutions or waivers, use of the MLAT in the diagnostic and course
      substitution/waiver process, and the validity and reliability of traditional
      criteria for the classification as LD are discussed.

PMID- 15510444
TI  - An intervention approach for children with teacher- and parent-identified
      attentional difficulties.
AB  - Using a multimodal and multi-informant method for diagnosis, we selected 33
      children by teacher and parent nomination for attention and work completion
      problems that met DSM-IV criteria for attention-deficit/hyperactivity disorder
      (ADHD). Of the 33 children in this group, 21 participated in the initial
      intervention, and 12 were placed in an ADHD control group and received the
      intervention after pre- and posttesting. A similarly selected group of 21
      children without difficulties in attention and work completion served as a
      control group. Each child was assessed on pre- and posttest measures of visual
      and auditory attention. After an 18-week intervention period that included
      attention and problem-solving training, all children in the intervention and
      control groups were retested on visual and auditory tasks. Children in both ADHD
      groups showed significantly poorer initial performance on the visual attention
      task. Whereas the ADHD intervention group showed commensurate performance to the
      nondisabled control group after training, the ADHD control group did not show
      significant improvement over the same period. Auditory attention was poorer
      compared to the control group for both ADHD groups initially and improved only
      for the ADHD intervention group. These findings are discussed as a possible
      intervention for children with difficulties in strategy selection in a classroom
      setting.

PMID- 15510445
TI  - PET scanning explained.
AB  - A fixed PET scan unit can be placed into an existing diagnostic or treatment
      space with a certain amount of renovation or an addition may be built to house
      the PET scanner as well as required support spaces. Approximately 2,000 ft2 is
      needed to house a full PET scan operation although this can change substantially
      depending upon individual circumstances. Typically included are the PET scan room
      that resembles a CT scan facility, a hot lab (if not shared), equipment control
      room, patient waiting, patient prep area, and a patient toilet. Some spaces may
      need to be lead-lined, depending on uses of adjacent space. Patient throughput'
      ranges from 45 minutes to one hour and 15 minutes to complete a scan, depending
      on equipment.

PMID- 15510446
TI  - Improving health sector travel.
AB  - Preventing ill health and obesity and building more physical activity into our
      daily lives have never been so high on the agenda, and the way we travel can
      help. Many workplaces and schools are drawing up travel plans, with the aims
      usually to minimise car use and encourage healthier and more environmentally
      friendly travel. The Transport White Paper of 1998 advocated travel plans and
      singled out hospitals for action. Travel plans continue to be a focus within the
      latest Transport White Paper, launched in July 2004. This article covers various
      prompts to the health sector to implement travel plans. It addresses issues and
      concerns facing NHS Trusts, the practical things Trusts can do, and the
      increasing amount of good practice available. Finally, it demonstrates that
      travel plans can work, and are working, in the health sector.

PMID- 15510448
TI  - All systems go for superb event.

PMID- 15510447
TI  - Procurement key to improved care.
AB  - For many, good health and "bricks and mortar" could not be further apart, but
      with daily headlines berating failing hospitals and poor working conditions there
      is an increasing realisation that premises can have a resounding impact upon
      services. Since its introduction in 2000, ProCure21 has played a major part in
      highlighting the importance of partnering between the public sector and the
      construction industry, helping to improve the standard of premises, and
      ultimately the services delivered to patients. But with the recent abolition of
      NHS Estates, ProCure21 and its achievements to date face significant threat.
      Anyone who has had the ill-fortune of a recent stay in hospital will appreciate
      the difference that a few minor design.

PMID- 15510449
TI  - FM services have vital role.
AB  - This article is based on an on-going PhD research study which includes the
      investigation of the role of facilities management (FM) in the control of
      Healthcare Acquired Infections (HAI).

PMID- 15510450
TI  - 'Hospital electrics' challenge.

PMID- 15510451
TI  - Insights into facility access.
AB  - Hospitals and healthcare premises are extremely busy environments, having to cope
      with continuous streams of high volume traffic, which includes stretchers and
      wheelchairs. With time of the essence, it is imperative that staff and patients
      have easy, reliable access throughout the building.

PMID- 15510452
TI  - Room for improvement.
AB  - First announced in 1992 by the then Conservative Government, the Private Finance
      Initiative is a contract whereby private companies finance, design, build and
      manage public buildings, such as hospitals and schools, and lease them to the
      public sector for a set period--typically 30 years. In healthcare, the scheme has
      been particularly prolific, with 34 hospitals and 119 other PFI health schemes
      built to date. PFI projects are also expected to account for the majority of the
      15 NHS hospital developments worth over pound 4 billion, that were recently
      announced by Health Secretary John Reid. Arguments aside, few could deny that PFI
      has been instrumental in facilitating the biggest NHS hospital building programme
      ever seen.

PMID- 15510453
TI  - Improving fire safety in hospital premises.
AB  - According to the latest statistics from the Office of the Deputy Prime Minister,
      the total figures for fires in hospitals and medical care facilities from the
      last recorded five years are revealed, in aggregate, to be 10% higher than 1998
      levels. A concurrent rise in false alarms has also been seen due to "apparatus"
      malfunction.

PMID- 15510454
TI  - Integration provides all-round benefits.
AB  - With the Government demanding greater value from its vast NHS expenditure, there
      have been many initiatives to drive cost out of the NHS often by extracting
      better deals from suppliers.

PMID- 15510455
TI  - Tactile signage leads the way.
AB  - As implementation of Part III of the 1995 Disability Discrimination Act draws
      closer, service providers are looking to their obligations and how they can
      fulfil them in a cost-effective way. Most sighted people assume that blind or
      visually impaired people read Braille and therefore Braille signage is a
      perfectly adequate measure. In fact this is a misconception.

PMID- 15510456
TI  - Eye banking--are we really up to it in India?

PMID- 15510457
TI  - Glaucoma in aphakia and pseudophakia after congenital cataract surgery.
AB  - Glaucoma is one of the most common causes of visual loss despite successful
      congenital cataract surgery. The overall incidence does not appear to have
      decreased with modern microsurgical techniques. The onset of glaucoma may be
      acute or insidious and notoriously refractory to treatment. Angle closure
      glaucoma may occur in the early postoperative period; but the most common type of
      glaucoma to develop after congenital cataract surgery is open angle glaucoma.
      Several risk factors have been identified and both chemical and mechanical
      theories have been proposed for its pathogenesis. Unlike children with congenital
      glaucoma, those with paediatric glaucoma following congenital cataract surgery
      are usually asymptomatic despite high intraocular pressure. They may require
      regular evaluation under anaesthesia, whenever there are any suspicious findings.
      Unlike congenital glaucoma, the first line of treatment for glaucoma in
      aphakia/pseudophakia may be medical. Traditional trabeculectomy in paediatric
      glaucoma following congenital cataract surgery has met with limited success. The
      addition of antimetabolites to trabeculectomy is known to inhibit fibrosis and
      enhance the success, but carries the lifelong risk of bleb-related
      endophthalmitis. Drainage implant surgery is a viable option to achieve longterm
      intraocular pressure control in this refractory group of patients. Cycloablative
      procedures may provide temporising treatment and should be reserved for patients
      with low visual potential. Diagnosis of glaucoma following congenital cataract
      surgery requires lifelong surveillance and continuous assessment of the problem.
      Further research is needed to understand the pathophysiology, prevention and
      treatment of this sight-threatening complication following successful cataract
      surgery in children.

PMID- 15510458
TI  - Macular thickness evaluation using the optical coherence tomography in normal
      Indian eyes.
AB  - PURPOSE: To determine the normative values for macular thickness and volume by
      Optical Coherence Tomography (OCT 3) in healthy Indian subjects. METHODS: The
      macula of 170 consecutive, randomly selected normal subjects was imaged on OCT 3
      in this cross-sectional study. OCT parameters of macular thickness were analysed
      with baseline variables including age, gender, axial length and refractive error.
      RESULTS: The average foveal thickness in the population under study was 149.16 +/
      21.15 micro. Macular thickness and volume parameters of OCT correlated
      significantly (Pearson's Correlation coefficient) with age (r=0.23, P<0.01), but
      not with gender, axial length and refraction. CONCLUSIONS: The macular thickness
      and volume parameters have a significant correlation with age. This normative
      database of macular thickness by OCT in Indian eyes may be a useful guideline for
      management and further research in diseases of the macula and glaucoma.

PMID- 15510459
TI  - Macular ischaemia as a marker for nephropathy in diabetic retinopathy.
AB  - PURPOSE: To determine whether diabetic macular ischaemia is associated with
      ischaemic heart disease (IHD), hyperlipidaemia, hypertension (HTN) and
      nephropathy. METHODS: Prospective case-control study from January to December
      2001, involving 102 type 2 diabetic patients (aged 40-80 years), 59 with
      unilateral / bilateral macular ischaemia and 43 concurrent controls. Diabetic
      retinopathy was graded and macular ischaemia assessed by fundus examination,
      central fundus photography and fluorescein angiography. Systemic examination and
      laboratory investigations were done to evaluate systemic diseases. The
      associations were analysed by Chi-square test and Student's t-test. The
      significance of the variables as independent risk factors was tested by logistic
      regression analysis. RESULTS: Macular ischaemia was not associated with IHD
      (P=1.00); HTN (P=1.00) and hyperlipidaemia (P=0.30). Nephropathy was
      significantly associated with macular ischaemia (P=0.025; odds ratio [OR]: 2.62;
      95% confidence interval [CI]: 1.16-5.9). The association remained significant
      after controlling for age, gender, duration of diabetes, severity of retinopathy,
      HTN, IHD and hyperlipidaemia. Further, the association with nephropathy was not
      affected by the presence of macular isachaemia in one or both the eyes (P=0.39).
      CONCLUSION: Macular ischaemia may serve as a marker for nephropathy in type 2
      diabetes mellitus irrespective of the severity of retinopathy.

PMID- 15510460
TI  - Modified needle drainage. A safe and efficient technique of subretinal fluid
      drainage in scleral buckling procedure.
AB  - PURPOSE: To compare modified needle drainage (MND) with conventional drainage
      (CD) of subretinal fluid (SRF) as described by Schepens in surgery for primary
      rhegmatogenous retinal detachment. METHODS: Prospective randomised clinical trial
      of 80 patients undergoing scleral buckling with subretinal fluid drainage for
      primary rhegmatogenous retinal detachment. In 40 patients modified needle
      drainage of subretinal fluid (SRF) was done using a perpendicular trans-scleral
      entry with a 26-gauge needle and the appearance of SRF in the hub of needle as
      end point. In 40 patients conventional drainage was done as described by Schepens
      using a diathermy needle. Adequacy of SRF drainage, intraoperative complications,
      anatomical and functional outcome were noted. RESULTS: 100% adequate drainage was
      achieved in all cases. The complication rate was 32.5% (n=13) in the CD group and
      15% (n=6) in the MND group. In the CD group, 17.5% (n=7) patients had subretinal
      haemorrhage and in 2 eyes it was clinically significant. In the MND group 15%
      (n=6) of cases had subretinal haemorrhage and in one patient it was clinically
      significant. In the CD group, more serious SRF drainage complications were
      observed; these were absent in the MND group. CONCLUSION: Modified needle
      drainage is a safe and effective procedure for SRF drainage. In comparison with
      CD, MND is technically easy, less cumbersome and requires no special equipment.

PMID- 15510461
TI  - Retinal nerve fiber layer measurements in indian eyes using the scanning laser
      polarimeter, GDx.
AB  - PURPOSE: To obtain retinal nerve fiber layer (RNFL) measurements in normal Indian
      subjects of different age groups; and to determine the differences between the
      right and the left eye of a subject and variations between male and female gender
      using the scanning laser polarimeter GDx. MATERIALS AND METHODS: Prospective
      cross-sectional study of 180 eyes of 94 subjects. The RNFL values were obtained
      with the nerve fiber analyser GDx using default quadrant positions supplied by
      the manufacturer. Fourteen parameters were studied. Of these 6 were average-based
      parameters (average thickness, superior maximum, inferior maximum, ellipse
      average, superior average, inferior average), 4 ratio-based parameters (symmetry,
      superior ratio, inferior ratio, superior/nasal), 4 "other" parameters (maximum
      modulation, number, ellipse modulation, superior integral). The main outcome
      measures were effect of age on RNFL values, comparison of males and females and
      the right and the left eye of a subject. RESULTS: There was a negative linear
      correlation with age. Three ratio-based parameters showed a statistically
      significant negative correlation with age. "Number" increased with age. Superior
      maximum, superior average, superior integral, symmetry and superior ratio were
      higher for the left eye. 'Number' was higher for the right eye. Superior ratio
      and maximum modulation were more in females than males, no difference was noted
      with other parameters. CONCLUSION: There was a gradual decrease of RNFL values
      with increasing age - the superior quadrant values were higher for the left eye
      than the right eye, suggesting asymmetry. No significant differences were
      detected between males and females.

PMID- 15510462
TI  - Myoconjunctival enucleation for enhanced implant motility. result of a randomised
      prospective study.
AB  - PURPOSE: Implant motility and cosmetic appearance of the eye after enucleation
      have remained major considerations whenever mycoconjunctival enucleation is
      planned. Despite major advances in surgical technique and the availability of a
      variety of implant materials and shapes, there is lack of consensus on the best
      material and type of implant. This study was conducted to compare routine and
      myoconjunctival techniques of enucleation in terms of motility index. METHODS:
      Thirty consecutive patients scheduled for enucleation for non-malignant
      indications were randomly assigned to one of the two groups- routine and
      myoconjunctival techniques. The postoperative results were compared for the
      motility of implant and the complications. RESULTS: The two techniques showed no
      difference in rates of complications, but implant motility was significantly
      better with the myoconjunctival technique. Implant extrusion or migration was not
      seen. CONCLUSION: We recommend the use of myoconjunctival enucleation for
      enhanced motility and cosmesis.

PMID- 15510463
TI  - Verteporfin therapy for myopic choroidal neovascularisation in Indian eyes (one
      year results).
AB  - PURPOSE: To investigate the 12 months' follow-up outcome of photodynamic therapy
      (PDT) with verteporfin for CNV in pathologic myopia in pigmented eyes of patients
      from the Indian subcontinent. METHODS: Nine eyes of 9 consecutive patients were
      included in the study. Patients with a spherical equivalent of - 6 diopter or
      more and baseline visual acuity of 6/60 or better were included. All patients
      received ETDRS visual acuity test (including letter acuity) and fluorescein
      angiography both before and after PDT. All patients had at least 12 months of
      follow up. RESULTS: The final visual acuity was unchanged 8 eyes (88.8% had VA of
      6/30 or better) at the end of 12 months. Six eyes (66.7%) lost < or = 8 letters
      and three eyes (33.3%) lost < or = 15 letters at the end of 12 months from the
      baseline. CONCLUSION: Photodynamic therapy with verteporfin for subfoveal
      choroidal neovascularisation secondary to high myopia tends to stabilise the
      vision at 12 months follow up in Indian eyes. Longer follow up is necessary to
      understand the natural history of CNV treated with PDT in high myopia in Indian
      eyes.

PMID- 15510464
TI  - Learning phacoemulsification. Results of different teaching methods.
AB  - We report the learning curves of three eye surgeons converting from sutureless
      extracapsular cataract extraction to phacoemulsification using different teaching
      methods. Posterior capsule rupture (PCR) as a per-operative complication and
      visual outcome of the first 100 operations were analysed. The PCR rate was 4% and
      15% in supervised and unsupervised surgery respectively. Likewise, an uncorrected
      visual acuity of > or = 6/18 on the first postoperative day was seen in 62 (62%)
      of patients and in 22 (22%) in supervised and unsupervised surgery respectively.

PMID- 15510465
TI  - A case of subcutaneous dirofilariasis of the eyelid in the South Indian state of
      Kerala.
AB  - This report describes a case of dirofilariasis of the upper eyelid of a young
      female patient from Kerala. This is probably the first reported case from India
      in which a live dirofilarial worm was recovered from the subcutaneous tissues of
      the eyelid.

PMID- 15510466
TI  - Lattice corneal dystrophy type III with corneal fistula. A case report.
AB  - Lattice corneal dystrophy is a distinct clinical entity characterised by amyloid
      deposits in the corneal stroma. We report a patient who presented with a corneal
      fistula in the right eye and thick lattice lines involving the peripheral cornea
      in both eyes suggestive of type III lattice dystrophy. The association of corneal
      fistula with lattice corneal dystrophy type III makes this a unique case.

PMID- 15510467
TI  - Choroidal melanoma with macular hole.
AB  - A rare case of choroidal melanoma with exudative retinal detachment and a full
      thickness macular hole is reported in an Indian patient.

PMID- 15510468
TI  - Posterior scleritis presenting as unilateral secondary angle-closure glaucoma.
AB  - The following is a case report of a 19-year-old male who presented with
      unilateral acute angle-closure glaucoma. Posterior scleritis was diagnosed based
      on clinical features and ultrasound B-scan. The acute angle closure attack and
      exudative retinal detachment completely resolved with use of oral
      corticosteroids.

PMID- 15510469
TI  - Orbital dermoid cyst with intracranial extension.
AB  - A case of dermoid cyst with intracranial extension in a 10-year-old boy is
      reported. Intracranial extension of dermoid is not very common.

PMID- 15510470
TI  - A pilot study on awareness of diabetic retinopathy among non-medical persons in
      South India. The challenge for eye care programmes in the region.
AB  - This study was conducted to determine awareness and practices relating to
      diabetic retinopathy among non-medical persons in a south Indian population. In
      this population-based cross-sectional study, trained social workers conducted
      face-to-face interviews using a semi-structured questionnaire with 200 randomly
      selected paramedical personnel and 204 persons randomly selected from the
      community. Responses were graded on a five-point scale. Over half of respondents
      were not aware of risk factors for diabetic retinopathy. Only one-fifth of
      paramedics and one-tenth of persons from the community were aware that
      uncontrolled diabetes was a risk factor for retinopathy. Over 75% of respondents
      were not aware of either laser or surgery as an intervention for retinopathy.
      Although 80% of respondents from the community felt that yearly eye examinations
      were essential, only 43.5% had ever visited an ophthalmologist. Nearly three
      fourths of paramedical personnel did not have any material related to diabetes
      for health education. It is evident that considerable effort is required to
      improve awareness of diabetic retinopathy, and to translate this improved
      awareness to actual utilisation of services.

PMID- 15510471
TI  - Bilateral submacular abscess after induced abortion.

PMID- 15510472
TI  - Leutic chorioretinitis in an immunocompromised patient.

PMID- 15510473
TI  - Major ocular complications after organ transplantation.

PMID- 15510474
TI  - Ocular manifestations of Behcet's disease in Indian patients.

PMID- 15510475
TI  - Ocular hypertension.

PMID- 15510476
TI  - Macular hole surgery.

PMID- 15510477
TI  - Phacoendophthalmitis.

PMID- 15510478
TI  - Transpupillary thermotherapy for choroidal neovascular membrane in age related
      macular degeneration.

PMID- 15510479
TI  - [Prevalance of open angle glaucoma and ocular hypertension as a risk factor for
      primary open angle glaucoma in Wroclaw population. Wroclaw Epidemiology Study].
AB  - OBJECTIVE: The purpose of the study is to assess the prevalence of various types
      of open angle glaucoma (OAG) and ocular hypertension (OH) as a risk factor for
      AOG. The second aim of the study was to determine the detection level of glaucoma
      in the population of Wroclaw inhabitants aged 40-79. MATERIAL AND METHODS: The
      population based cross-sectional sample of 4853 Wroclaw inhabitants aged 40-79
      years underwent two stage examination. First stage of the study included medical
      history interview and five screening tests: tonometry, peripheric anterior
      chamber depth assessment by Van Herick technique, ocular nerve head (ONH)
      assessment by stereoscopic ophthalmoscopy, Heidelberg Retina Tomograph (HRT) and
      Nerve Fiber Analyzer (GDx) investigation. Second stage included complete
      ophthalmological examination with gonioscopy, static perimetry and 24 hours
      monitoring of intraocular pressure (IOP), and pachymetry in OH group. RESULTS:
      The prevalence of glaucoma in Wroclaw population aged 40-79 years was 1.6%. Open
      angle glaucoma (OAG) that includes primary open angle glaucoma (POAG), normal
      pressure glaucoma (NPG) and capsular glaucoma (PEX-glaucoma) was found in 1.53%
      of the population. Glaucoma detection level was low: 71% of all cases of glaucoma
      were diagnosed for the first time. The percentage of OH detected in Wrodaw
      population was 1.9%. Following the criteria of Ocular Hypertension Treatment
      Study (OHTS) we found that the pachymetric value of central corneal thickness
      (CCT) in OH group was less than 555 microm (thin cornea) in 12.5%, from 555
      microm to 588 microm (normal thickness of central cornea) in 26.14% and more than
      588 microm (thick cornea) in 61.36% of the subjects. CONCLUSIONS: The Wroclaw
      Epidemiological Study revealed OAG as 91% of overall glaucoma cases. The
      relatively high percentage of glaucoma cases was diagnosed for the first time.
      This number is higher than reported by other authors of population studies in
      white communities. In the OH group the 26.14% of the eyes with normal CCT has
      increased risk, and the 12.5% eyes with thin cornea has highly increased risk of
      POAG, according to OHTS results.

PMID- 15510480
TI  - [Loss of heterozygosity at microsatellite marker localised near the
      metalloproteinase gene in patients with PEX syndrome].
AB  - PURPOSE: The aim of the study was to evaluate the possible occurrence of loss of
      heterozygosity (LOH) at microsatellite marker localised near the area for
      metalloproteinase gene in the anterior capsule, lens nucleus, iris and trabeculum
      samples taken from patients with pseudoexfoliation syndrome (PEX). MATERIAL AND
      METHODS: In our study we examined 19 patients (12 women and 7 men) with PEX
      syndrome who underwent surgical treatment for glaucoma, cataract or both at the
      same time. The mean age was 75.5 +/- 4.7, range 64-86. Specimens of the iris,
      anterior capsule, trabeculum and lens nucleus were taken to evaluate the possible
      occurrence of LOH at microsatellite marker D7S820 with fluorescent multiplex PCR
      method. RESULTS: LOH was displayed in 44% specimens of anterior capsule, 33% of
      iris specimen. In lens nucleus and trabeculum specimen LOH did not occur.
      CONCLUSIONS: The high frequency of LOH in PEX patients at locus D7S820 suggests
      that genetic factors may be involved in the etiology and pathogenesis of PEX.

PMID- 15510481
TI  - [The expression of Bcl-2, Bcl-xl, Bak and Bax proteins in axons of the optic
      nerve in closed-angle glaucoma].
AB  - PURPOSE: The aim of our study was the evaluation of Bcl-2, Bcl-xl, Bak and Bax
      immunoexpression in axons of the optic nerve with absolute glaucoma. MATERIAL AND
      METHODS: This study was conducted on 19 patients with absolute glaucoma, suffered
      from severe ophthalmalgia, treated of necessity by enucleation in 1991-2003 in
      our Department of Ophthalmology. The samples were immuno-stained with antibodies
      for Bcl-2, Bak, Bax and Bcl-xl protein. The reactions were performed in Labelled
      Streptavidin Avidin Biotin (LSAB) technique. The evaluation of immuno-staining
      was calculated as the percentage of cells with positive reaction to the total
      number of cells encountered in 10 representative fields, by light microscopy
      using a x 20 objective lens. Scores were based on the following scale: (++), over
      50% of the field showing positive immuno-staining, (+) 10-50% with positive
      immunostaining. RESULTS: In our study proapoptotic Bak and Bax protein expression
      was stronger than antiapoptotic Bcl-2, Bcl-xl protein expression; Bak/Bcl-2 (p =
      0.008), Bax/Bcl-2 (p = 0.0007), Bak/Bcl-xl (p = 0.0356), Bax/Bcl-xl (p = 0.0077).
      CONCLUSIONS: The results of our study demonstrate high proapoptotic trends in
      axons of the optic nerve in the stage of absolute glaucoma.

PMID- 15510482
TI  - [Nitric oxide level in aqueous humor in patients with glaucoma].
AB  - PURPOSE: There is increasing evidence suggesting, that nitric oxide may be
      implicated in the pathogenesis of glaucoma. The aim of the study was to evaluate
      nitric oxide level in aqueous humor of glaucoma patients. MATERIAL AND METHODS:
      The examined group was constituted by 26 persons (13 women and 13 men), aged 60
      86 (mean age 70) suffering from glaucoma. In 14 patients glaucoma was classified
      as POAG and in 12 as PACG. All patients have undergone trabeculectomia. The 14
      patients was operated because of age-related cataract (8 women and 6 men), aged
      47-82 (mean age 65), constituted a control group. All patients agreed to samples
      collection. Level of nitric oxide in anterior chamber fluid was assessed using
      commercial kits based on Griess reaction (R&D) according to manufacturer's
      instruction. Statistical analysis was performed using U Mann-Whitney test.
      RESULTS: The mean level of nitric oxide in aqueous humor was not significantly
      different between glaucoma and cataract group (p=0.535). The level of NO in humor
      aqueous was statistically significantly lower in patients with primary open angle
      glaucoma than in patients with primary angle closure (p=0.022), and than in
      control group (p=0.053). No statistically significant differences in the level of
      nitric oxide in humor aqueous between PACG and cataract patients were observed
      (p=0.365).

PMID- 15510483
TI  - [Antibodies to beta-2 glycoprotein I in serum and aqueous humor of patients with
      glaucoma and their influence on the static perimetry].
AB  - PURPOSE: The evaluation of the relationships between the antibodies anti beta-2
      glycoprotein I in serum and aqueous humor of the glaucoma patients to the visual
      field defects. MATERIAL AND METHODS: 48 persons (38 women and 17 men), aged 30-86
      (mean age 70), suffering from glaucoma was examined. There were 19 with POAG, 18
      with PACG and 11 with PEXG. All patients have undergone trabeculectomy. In plasma
      and anterior chamber fluid the level of antibodies to beta-2 glycoprotein I
      classes IgA and IgG were measured using ELISA method (commercial kits produced by
      Euroimmun), according to producer's instruction. The visual field defects were
      examined with Humphrey static perimetry. Statistical analysis was performed using
      Spearman test. RESULTS: There were no significant correlations between antibodies
      anti beta-2 glycoprotein I, static perimetry, age and duration of the disease.
      CONCLUSIONS: There have not been stated any relationships between the static
      perimetry to antiphospholipid antibodies level in serum and aqueous humor in
      patients with glaucoma. It is the preliminary communication.

PMID- 15510484
TI  - [Serum and aqueous humor antibodies to beta-2 glycoprotein I in patients with
      glaucoma and cataract].
AB  - PURPOSE: Evaluation of the serum and aqueous humor antibodies to beta-2
      glycoprotein I in patients with glaucoma. MATERIAL AND METHODS: 48 persons (38
      women and 17 men), aged 30-86 (mean age 70), suffering from glaucoma was
      examined. There were 19 with POAG, 18 with PACG and 11 with PEXG. All patients
      have undergone trabeculectomy. The group of 20 operated patients, because of age
      related cataracta (7 men and 13 women), aged 47-82 (mean age 65), constituted a
      control group. All patients agreed with samples collection. In plasma and
      anterior chamber fluid, the level of antibodies to b-2 glycoprotein I classes IgA
      and IgG were measured using ELISA method (commercial kits produced by Euroimmun),
      according to producer's instruction. Statistical analysis was performed using U
      Mann-Whitney test when both groups were compared and Spearman test to comparisons
      concerning single group. RESULTS: Significant changes between glaucoma and
      cataract patients were observed in anti-b-2 glycoprotein I antibodies class IgA
      in aqueous humour (p=0.04) and in serum (p=0.03). CONCLUSIONS: Knowledge of the
      immunological pathogenesis in the glaucomatous nerve damage can be curtailed or
      even prevented with the use of proper agents. Indeed, there are many intriguing
      new therapeutic possibilities on the horizon. To determine the clinical potential
      of serum antibodies in glaucoma patients, a randomized clinical trial would be
      necessary. It is the preliminary communication.

PMID- 15510485
TI  - [Intraoperative use of mitomycin C in glaucoma filtering surgery--indications,
      results and complications].
AB  - PURPOSE: The influence of MMC on the cornea, especially on the corneal
      endothelium and thickness, were checked. MATERIAL AND METHODS: In one-year-follow
      up patients after trabeculectomies with or without topical use of mitomycin C
      were controlled for early and late complications, and levels of intraocular
      pressure. The progression of glaucomatous neuropathy was obtained by comparing
      the cup to disc ratio and some parameters of static visual field testing (MD,
      PSD) progressions, after one year observations. RESULTS: Intraocular pressures
      were stable and at lower levels in the group of patients after primary
      trabeculectomies (group C) than in the control group (group A). We obtained good,
      statistically significant decrease in IOP in all groups during one year follow
      up. CONCLUSIONS: We didn't find any toxic effects of MMC, given on a sponge
      during trabeculectomy, on the morphology and physiology of the corneal
      endothelium and the central corneal thickness. We also didn't note any
      differences between groups in the progression of glaucomatous optic nerve damaged
      and cataract after 1 year follow up.

PMID- 15510486
TI  - [Non-penetrating deep sclerectomy in the treatment of advanced cases of open
      angle glaucoma].
AB  - PURPOSE: The purpose of the paper was to examine the efficacy of non-penetrating
      deep sclerectomy (NPDS) with sodium hyaluronate implants and mitomycin C in the
      treatment of advanced cases of open angle glaucoma. MATERIAL AND METHODS: Thirty
      five eyes of 35 patients with medically uncontrolled advanced open angle glaucoma
      were retrospectively analyzed. Visual acuity and intraocular pressure measurement
      were performed before and after surgery at 1 and 7 days and 1, 6 and 12 months.
      Visual field was analyzed before and 12 months after surgery. RESULTS: The mean
      preoperative intraocular pressure was 27+/-3.1 mm Hg and 18.1+/-1.5 at 12 month
      after surgery (p<0.05). Visual acuity decreased more than two rows on Snellen
      chart in 4 patients. Visual field analysis shows mean defect MD--17+/-5.2 before
      surgery and 20.1+/-6.2 after 12 month of follow up (p>0.05). Complete success
      rate defined as an IOP lower than 21 mmHg without medications was 51%. In 3 eyes
      we performed needling and in 8 goniopuncture. Postoperative complications
      included hyphaema in 3 eyes, choroidal detachment in 1 eye, bleb fibrosis in 2
      eyes. CONCLUSIONS: 1. Deep sclerectomy with SK-GEL implant and antimetabolites
      provided good reasonable control of intraocular pressure. 2. In uncomplicated
      cases it let us achieve stabilization of the visual field.

PMID- 15510487
TI  - [Implantation of Ahmed-type valve in the treatment of glaucoma, following
      penetrating keratoplasty].
AB  - PURPOSE: To evaluate the outcomes of Ahmed glaucoma valve implantation for
      therapy of glaucoma after penetrating keratoplasty. MATERIAL AND METHODS: 17
      Ahmed glaucoma valve implants were placed in 17 eyes with glaucoma after
      penetrating keratoplasty. The follow up was 1 year. V.A., IOP and index
      medication were observed before and 1 year after surgery. RESULTS: The mean
      preoperative IOP was 29.1 mmHg (+/-6.5) with average medication 2.65 +/- 0.5, 1
      year after surgery the mean IOP decreased to 18.4 mmHg +/- 4.7 with 0.7 +/- 0.8
      medication. The tube implant successfully controlled glaucoma in 13 eyes (73.5%)
      at 1 year. The corneal grafts remain clear in 11 eyes (64.7%). CONCLUSIONS:
      Implantation of Ahmed glaucoma valve successfully controlled IOP in difficult
      cases of glaucoma after penetrating keratoplasty.

PMID- 15510488
TI  - [Non-penetrating deep sclerectomy with SK-GEL implant in the patients with
      pseudoexfoliation glaucoma].
AB  - PURPOSE: The aim of this study was to evaluate the effectiveness of non
      penetrating deep sclerectomy with SK-GEL implant in the patients with
      pseudoexfoliation glaucoma. MATERIAL AND METHODS: Non-penetrating deep
      sclerectomy with SK-GEL implant was performed in 5 eyes of 5 patients aged 65 to
      78 (mean age 73 years +/- 5.4). Pseudoexfoliation glaucoma was recognized in all
      patients. In spite of the intensive pharmacological and laser treatment,
      sufficient reduction of an intraocular pressure was not obtained. The intraocular
      pressure before the surgery ranged between 24 and 43.4 mmHg (mean 31 mmHg +/-
      7.6). Follow-up period lasted from 36 to 53 days (mean 46 days +/- 7.7). RESULTS:
      After the surgery, reduction of the intraocular pressure was observed in all
      subjects. At the moment of discharge from hospital the intraocular pressure
      ranged from 12 to 26 mmHg (mean 19.6 mmHg +/- 5.12), and at the last control
      appointment--from 14 to 16 mmHg (mean 14.9 mmHg +/- 0.72). CONCLUSIONS: Non
      penetrating deep sclerectomy with SK-GEL implant can be taken into consideration,
      while planning glaucoma surgery in the patients with pseudoexfoliation syndrome.

PMID- 15510489
TI  - [Long-term results of trabeculectomy in patients with open angle and angle
      closure glaucoma].
AB  - PURPOSE: To provide data on the long-term results of trabeculectomy performed in
      open angle and in chronic angle-closure glaucoma. MATERIAL AND METHODS: Fifty
      nine eyes of 51 patients, underwent trabeculectomy from 1992 to 1994 in the
      Department of Ophthalmology, Medical University of Lodz. The follow up was
      minimum 10 years. Such pre- and postoperative measurements, as: visual acuity,
      intraocular pressure (IOP), visual field and the use of hypotensive medications,
      were evaluated. RESULTS: Successful IOP control was obtained in 91%. After 10
      years follow-up the average IOP was 15 mmHg. The decrease in visual acuity was
      found in 25% of eyes, caused mainly by cataract. In 71% of eyes (10 years after
      surgery) additional topical medication was required. CONCLUSIONS: Trabeculectomy
      is effective and very often performed surgery in glaucoma.

PMID- 15510490
TI  - [Risk factors for encapsulated filtering bleb after trabeculectomy--own
      experience].
AB  - The aim of the study was to evaluate the incidence of encapsulated filtering bleb
      at patients after trabeculectomy. We analyzed risk factors, prognosis and
      treatment in cases of this complication. All 857 cases of trabeculectomies
      performed in Department of Ophthalmology of Medical University of Warsaw in years
      2001-2003 were included in the study. Twenty two cases (2.5% of all
      trabeculectomies) of encapsulated filtering bleb were analyzed. Twenty patients
      (91%) underwent surgery procedure and two patients (9%) were treated medically.
      The encapsulated filtering blebs occurred mainly in patients after previous
      ocular surgery, in eyes with episodes of earlier ocular inflammation and in
      patients treated with many antiglaucoma drops.

PMID- 15510491
TI  - [Intrascleral placement of peripheral iris as a method of advanced glaucoma
      surgery].
AB  - PURPOSE: The main purpose of the study was to demonstrate the procedure and
      evaluate efficacy of intrascleral placement of peripheral iris as a method of
      treatment in advanced glaucoma cases. MATERIAL AND METHODS: 24 patients with
      advanced glaucoma were enrolled in the study. Surgery was performed. The IOP was
      measured before the surgery, 5 days, 1 month and 6 months after the surgery. The
      effectiveness of treatment and rate of complications were assessed. RESULTS:
      Average IOP after surgery significantly decreased from 46.16 +/- 8.99 mmHg to
      14.33 +/- 4.59 at the 5th day after the surgery, 17.20 +/- 3.88 at 1 month and
      17.75 +/- 4.09 at 6 months. The efficacy of treatment was 91.66% at 5th day,
      87.5% at 1 month and 83.33% at 6 months. CONCLUSIONS: The findings of the study
      suggest that this technique is effective in advanced glaucoma cases and is
      associated with low complication rate.

PMID- 15510492
TI  - [Phacoemulsification of subluxated opacified lens in pseudoexfoliation glaucoma
      patients, performed with the use of a capsular tension ring and iris retractors].
AB  - PURPOSE: To evaluate results of phacoemulsification of subluxated lens in
      patients suffering from pseudoexfoliation-related cataract and glaucoma,
      performed with the use of a capsular tension ring (CTR) and iris retractors and
      implantation of artificial intracapsular lens. PATIENTS AND METHODS: The
      retrospective covered 15 patients (15 eyes) at the average age of 75 years, with
      a subluxated, cloudy lens and pseudoexfoliation glaucoma with IV PEX. Due to poor
      mydriasis resulting from the course of the pseudoexfoliation syndrome, it was
      necessary with all the patients to apply iris retractors in order to enlarge the
      pupil. The opacified lens were removed by means of phacoemulsification. In order
      to provide additional peripheral support and to maintain the artificial lens in
      the central position after the surgery, a tension ring was implanted into the
      lenticular capsule. A foldable intraocular lens was implanted inside the capsule.
      RESULTS: The observation period was 12 months. The average visual acuity prior
      the surgery was 0.18+/-0.2, while after a year after the surgery it was 0.56+/
      0.32 (p<0.001). Besides, the intraocular pressure was observed to decrease from
      18.2+/-5.02 mm Hg before the surgery to 15.8+/-0.84 mmHg (p<0.001) after the
      surgery. The anti-glaucoma medication ratio was also reduced from 2.1 to 1.3 in
      the post-surgery period. Inflammatory reaction of the anterior chamber was
      observed in 7 eyes. CONCLUSIONS: Application of a CTR and iris retractors during
      a surgery of cataract in patients with subluxated opacified lens considerably
      facilitates the implantation procedure of an artificial lens into the capsule,
      and it allows to improve the visual acuity and stabilize the intraocular pressure
      while reducing the quantity of the applied anti-glaucoma drugs.

PMID- 15510493
TI  - [Comparative analysis of the results of modified sinusectomy and trabeculectomy
      in patients with primary open angle glaucoma].
AB  - PURPOSE: A study was conducted to examine surgical approach for the management of
      patients with open-angle glaucoma, in which Schlemm's canal is opened to restore
      drainage in a non penetrating fashion. Compared over the results of the surgical
      procedure including new modification of sinusectomy with the results of standard
      trabeculectomy. MATERIAL AND METHODS: The study concerns 82 patients with primary
      open angle glaucoma. A new type of surgical procedure performed on 40 consecutive
      patients (Group I). Trabeculectomy performed on 42 patients (Group II). Data,
      including visual acuity, intraocular pressure, complications and the number of
      medications required to maintain adequate pressures, were analyzed. The follow-up
      time ranged from 6 months to 3 years. RESULTS: After 24 months postoperatively,
      88.4% (Group I) and 91% (Group II) of the patients achieved an intraocular
      pressure lower than 21 mmHg. CONCLUSIONS: The non penetrating technique to open
      the canal effectively, allows the drainage of aqueous to acceptable levels,
      without the complications associated with trabeculectomy.

PMID- 15510494
TI  - [Phacotrabeculectomy in patients with cataract and chronic open angle glaucoma,
      and patients with cataract and pseudoexfoliation glaucoma].
AB  - PURPOSE: To compare the results obtained after phacotrabeculectomy followed by
      implantation of an intracapsular lens in patients with cataract and chronic open
      angle glaucoma, and patients with cataract and pseudoexfoliation open angle
      glaucoma. MATERIAL AND METHODS: The retrospective study covered 55 eyes with
      cataract and glaucoma. In 28 eyes, chronic open angle glaucoma was diagnosed, and
      in 27--pseudoexfoliation glaucoma. In all cases, phacoemulsification of the
      opacified lens was carried out, a foldable intraocular lens was implanted in the
      capsule, and the trabeculum was removed by means of a punch. Visual acuity,
      intraocular pressure and the ratio of applied anti-glaucoma drugs were subject to
      the assessment. RESULTS: The observation period was 12 months. Within the COAG
      patient group, the average visual acuity prior to the surgery was 0.2+/-0.24, and
      after one year from the surgery it increased to 0.82+/-0.22. For PEX glaucoma
      patients, the values were respectively 0.3+/-0.25 before the surgery and 0.75+/
      0.29 a year after it. Considerable reduction of the intraocular pressure was also
      achieved: in the COAG patients--from 19.51+/-3.8 mm Hg to 16.6+/-1.6 mm Hg, and
      in PEX glaucoma patients--from 22.28+/-5.18 mm Hg to 17.6+/-2.33 mm Hg one year
      after the surgery. Also, the quantity of anti-glaucoma drugs applied in the study
      groups was significantly reduced. The anti-glaucoma drug ratio in the COAG
      patients dropped from 1.8 to 0 after the surgery, and in the PEX glaucoma
      patients--from 2.3 to 0.3. CONCLUSIONS: Phacotrabeculectomy is an efficient and
      safe surgical method, to be recommended for patients both with primary open angle
      glaucoma and with pseudoexfoliation glaucoma.

PMID- 15510495
TI  - [Surgical management of pathologic filtering blebs in pediatric glaucoma].
AB  - The aim of this paper is to present our own experience in the treatment of cystic
      blebs in children and young adults. This complication, which is the most popular
      after trabeculectomy with antimetabolic agents, can be the reason of late
      endophthalmitis. Surgical treatment is one of the method to prevent it. In the
      study 6 patients with cystic blebs after trabeculectomy with mitomycin C was
      presented. 4 of them was treated surgically. We described the method of surgery
      and the results.

PMID- 15510496
TI  - [Intraocular pressure in early postoperative period after cataract
      phacoemulsification].
AB  - PURPOSE: The purpose of this study was to investigate the pattern of intraocular
      pressure (IOP) change after phacoemulsification and its bearing on timing of
      postoperative review. MATERIAL AND METHODS: 31 eyes of 31 consecutive patients
      having uneventful phacoemulsification were included in this study. The IOP was
      measured by Goldmann applanation tonometry preoperatively and 1-3 hours, 1 day
      and 1 week postoperatively. The relationship between these measurements' readings
      were examined. RESULTS: 31 patients completed the study. The IOP checked next day
      was significantly correlated with the IOP preoperatively. CONCLUSION: After
      phacoemulsification with OIL implantation the decrease in IOP was observed in
      first three postoperative hours in comparison with preoperative values and it was
      followed by an increase on the first postoperative day. It decreased again after
      a week reaching values lower than preoperatively. Only in few cases (10%) a
      transient intraocular hypertension (23-26 mmHg) appeared on the first
      postoperative day.

PMID- 15510497
TI  - [Diode laser cyclophotocoagulation--effect on intraocular pressure in comparison
      with cyclodiathermy under the scleral flap].
AB  - The aim of this study was to retrospectively analyze intraocular pressure and
      state of the eyeball in patients treated with diode laser, and to compare the
      outcomes with a group of patients after cyclodiahtermy under the scleral flap. We
      analyzed: visual acuity, IOP, percentage of lowering the IOP from the beginning,
      subjective patients' feelings of pain and complications. CONCLUSIONS: TSCPC is
      safe for patients and may be repeated, if needed. Laser cyclodestruction gives
      new possibilities in noninvasive IOP lowering with less complications than
      cyclodiahtermy, without changes in patient's visual functions.

PMID- 15510498
TI  - [Cyclodestructive procedures in secondary glaucoma in children].
AB  - PURPOSE: Comparison of the effectiveness and safety of cyclocryocoagulation and
      transscleral contact cyclophotocoagulation with diode laser (TSCPC) in children.
      PATIENTS AND METHOD: Sixty nine eyes of 60 children at the age from 4 months to
      16 years were examined. Majority of patients was aphakic after congenital,
      traumatic and complicated cataract extraction. Aniridia, Sturge-Weber disease and
      ROP complications were observed. In 40 eyes cyclocryotherapy (I group), in 29
      eyes TSCPC (II group) were performed. Intraocular pressure (IOP) was assessed in
      the early and late postoperative period. The number of procedures per one eye,
      IOP, visual acuity, and complications after cyclodestructive procedures were
      estimated. Follow-up ranged from 3 months to 4 years, mean 23 months. RESULTS:
      Transscleral cyclocryocoagulations were performed once to 4 times in one eye with
      intervals from 1 month to 1 year, mean 1.3 procedures per eye. TSCPC was
      performed once in 29 eyes and twice in 4 cases, it was 1.14 procedures per eye.
      Before treatment IOP ranged from 21.3 to 50.6 mmHg, mean 29.18 mmHg in the I
      group and 24.4-54 mmHg mean 34.85 mmHg in the II group and in the early
      postoperative period were 10-25 mmHg, mean 17.7 and 2-26 mmHg, mean 14.65 mmHg
      relatively. Decreasing of IOP was observed in 39% of eyes after cryotherapy and
      57.9% after TSCPC, p = 0.0003. In the long-term follow-up in IOP below 22 mmHg
      after cyclocryotherapy in 60% of eyes and after TSCPC in 79% was observed. Visual
      acuity ranged from no light perception to 0.5, mean 0.04. No changes of vision
      after cyclocryocoagulation were noted. After TSCPC transient visual function
      decreased from 0.2 to 0.04 in 1 eye but recovered after 2 weeks. After
      cyclocryotherapy only conjunctival oedema was observed in majority of cases. In
      the early postoperative period after TSCPC uveitis occured in 3 eyes (10.35%),
      transient hypotony in 2 eyes, hyphaema in one eye. CONCLUSION: Diode
      cyclophtocoagulation decreases IOP more effective than cyclocryocoagulation in
      children but complications after TSCPC are more severe than after
      cyclocryotherapy.

PMID- 15510499
TI  - [Evaluation stereometric parameters of the optic nerve head in the III and IV
      stage of pseudoexfoliation syndrome].
AB  - PURPOSE: Pseudoexfoliation syndrome (PEX) often coexists with glaucomatous optic
      nerve head damage. Confocal scanning laser tomography Heidelberg Retina Tomograph
      (HRT) is the most competent and accurate technique of monitoring of glaucomatous
      optic nerve head damage. Our aim was to determine correlation between stage of
      PEX and glaucomatous optic nerve head damage, by using HRT system. MATERIAL AND
      METHODS: Two groups of patients underwent examination. The examined PEX-group
      with 35 eyes with III stage and 35 eyes with IV stage of PEX. The control group
      (POAG patients) of 44 eyes. Stereometric parameters Disc Area, Cup Area, Cup/Disc
      Area Ratio, Rim Area, Height Variation Contour, Cup Volume, Rim Volume, Mean Cup
      Depth, Max Cup Depth, Cup Shape Measure, Mean RNFL Thickness, RNFL Cross Section
      Area were obtained by HRT. RESULTS: No statistical differences were noted between
      III and IV stage of PEX for DA, HVC, RV, Mean RNFL Thickness and RNFL Cross
      Section Area parameters. Between III stage of PEX and control group no
      statistical differences were confirmed for HVC. Between IV stage of PEX and
      control group no statistical differences have respect to: CSM, Mean RNFL
      Thickness and RNFL Cross Section Area stereometric parameters. CONCLUSIONS: IV
      stage of PEX syndrome is the serious risk for glaucomatous neuropathy and
      requires precise monitoring.

PMID- 15510500
TI  - [Use of scanning laser ophthalmoscope and scanning laser polarimeter in diagnosis
      and monitoring of early stages of primary open-angle glaucoma].
AB  - PURPOSE: To evaluate the usefulness of scanning laser ophthalmoscope (TopSS) and
      scanning laser polarimeter (GDx) in diagnosis and monitoring patients suspected
      of primary open angle glaucoma (POAG). MATERIAL AND METHODS: In eighty eyes of 40
      patients, we performed TopSS, GDx and static perimetry (Octopus 123) in the time
      period of three years. RESULTS: The GDx analysis showed progression of changes in
      the retinal fiber thickness in 28 (35%) eyes (p<0.05). In 18 eyes we found non
      specific changes in GDx examinations, which were related to no glaucomatous
      reason. TopSS analysis of the optic nerve head revealed progression in c/d in 16
      (20%) eyes (p<0.05). In seven eyes we detected changes in the visual field, which
      were more strongly connected with changes in TopSS than GDx. CONCLUSIONS: 1. The
      TopSS and GDx examinations enabled diagnosis and monitoring of early glaucomatous
      changes in the period of observation. 2. The GDx examination seems to be more
      sensitive, and TopSS more specific to glaucoma.

PMID- 15510501
TI  - [Evaluation of blood-flow parameters in extraocular arteries in patients with
      primary open-angle glaucoma before and after surgical treatment].
AB  - PURPOSE: To determine blood-flow parameters in extraocular vessels in patients
      with primary open-angle glaucoma before and after trabeculectomy. MATERIAL AND
      METHODS: Between November and December 2002 in 18 patients (12 women and 6 men)
      with primary open-angle glaucoma trabeculectomy was performed. In preoperative
      period, 10 days after and between third and sixth month after trabeculectomy,
      patients were subjected to complete ocular examination and evaluation of blood
      flow velocity (mean, systolic, diastolic) and pulsation indexes in posterior
      ciliary arteries with Doppler focused pulsating ultrasonography. Based on the
      results of the last examination patients were divided in two groups before the
      treatment. Group A included 9 patients (4 men and 5 women), age ranged from 46 to
      77 (mean 63.67). Preoperative IOP in this group ranged from 14.6 mmHg to 34.5
      mmHg (mean 25.6 mmHg). Blood-flow velocities were lowered in 9 patients for 20%
      below the norm. Pulsation indexes ranged from 1.0 to 1.3 in 7 patients and from
      1.3 to 1.5 in 2 patients. Group B included 9 patients (6 women and 3 men) age
      ranged from 58 to 88 (mean 73.5). Preoperative IOP in this group ranged from 14
      to 44 mmHg (mean 27.24 mmHg). Blood-flow velocities were lowered in 9 patients
      for 30-50% below the norm and pulsation indexes were higher then 1.2. Three of
      the 9 described patients had no velocities in diastolic phase and pulsation
      indexes were higher than 2.0. RESULTS: Postoperative IOP in group A ranged from
      7.1 to 17.3 mmHg (mean 11.0 mmHg). Four of the 7 described patients had
      velocities higher for 20-30% than preoperatively and were normal. Pulsation
      indexes lowered to 1.0-1.2. In 3 patients velocity increase was observed later
      (after 6 months). In group B postoperative IOP ranged from 4.9 to 14.6 mmHg (mean
      8.6 mmHg). Velocity increase was observed and it reached the lower limit of the
      norm or were higher. Pulsation indexes lowered to 1.0-1.2. CONCLUSION: The
      parameters of blood-flow in posterior ciliary arteries improved in all cases
      after trabeculectomy.

PMID- 15510502
TI  - [Pulsatile ocular blood flow in patients with juvenile glaucoma].
AB  - PURPOSE: To compare ocular blood flow in patients with glaucoma juvenile and in
      normal subjects. MATERIAL AND METHODS: 20 glaucoma juvenile subjects and 20
      persons as a control group aged 13 and 17, were matched for intraocular pressure
      and pulsatile ocular blood flow using pulsatile ocular blood flow (POBF).
      RESULTS: A positive correlation was found between ocular blood flow in patients
      with glaucoma juvenile and normal subjects. CONCLUSIONS: 1) POBF is a new and
      simple tool for the measurement intraocular pressure and pulsatile ocular blood
      flow and may be useful for diagnosis of the glaucoma. 2) We found a significant
      difference between ocular blood flow in glaucoma juvenile patients and normal
      subjects.

PMID- 15510503
TI  - [Blood flow in eye arteries assessed by Doppler ultrasound in patients with
      myopia].
AB  - PURPOSE: To assess blood flow in eye arteries using ultrasounds in patients with
      myopia, and to correlate the blood flow with refractive error. MATERIAL AND
      METHODS: Doppler ultrasonography was performed in 38 patients, age 31-50 years
      old, with myopia ranging from -2.0 to -25.0 D. Control group consisted of age
      matched emmetropic patients. RESULTS: Statistically significant decrease of Vs
      correlated to the value of refractive error was shown. CONCLUSIONS: In myopic
      eyes blood flow decreases with the increase of the refractive error.

PMID- 15510504
TI  - [Assessment of blood flow in eye arteries in patients with myopia and glaucoma].
AB  - PURPOSE: To assess blood flow in eye arteries in patients with myopia and POAG.
      MATERIAL AND METHODS: Doppler ultrasonography was performed in 17 patients with
      myopia and POAG. The following parameters were statistically analyzed: ophthalmic
      artery Vs (Vs OA), ciliary arteries Vs (Vs CA), central retinal artery Vs (Vs
      CRA) and compared to a group of myopic eyes with no POAG and a group of
      emmetropic eyes with no POAG. RESULTS: Statistically significant decrease of Vs
      in all analyzed vessels was detected as compared to normal age ranges (a group of
      emmetropic eyes with no POAG). Statistically significant decrease of Vs in OA and
      CRA was detected as compared to Vs in myopic eyes with no POAG. CONCLUSIONS:
      Statistically significant decrease of Vs in patients with myopia and POAG
      indicates poor perfusion in eye ball vessels.

PMID- 15510505
TI  - [Papillary blood flow and morphological parameters of the optic nerve head in
      patients with normal tension glaucoma, primary open angle glaucoma and in healthy
      volunteers].
AB  - The aim of the present study was to compare selected morphological parameters of
      the optic nerve head and papillary blood flow in patients with NTG, POAG and in
      healthy volunteers, as well as to find any possible correlation between selected
      morphological parameters and papillary blood flow. 21 glaucomatous and 31 normal
      eyes were diagnosed using HRT and HRF. Statistically significant differences
      within many morphological parameters like cup area, cup to disc, cup shape
      measure, rim volume, RFNL thickness, RFNL cross section and neuroretinal rim
      blood flow appeared. Nevertheless, in glaucoma patients no statistically
      significant differences between morphology and flow were found. The conclusion is
      that blood flow impairment within the neuroretinal rim is connected with glaucoma
      neuropathy development, nevertheless it is affected by other factors.

PMID- 15510506
TI  - [Frequency doubling perimetry in diagnosis of early glaucomatous optic nerve
      fiber damage].
AB  - PURPOSE: The comparative evaluation results of frequency doubling technology
      (FDT) in healthy subjects, in patients with glaucoma suspected and glaucoma, as
      well as analysis influences of selected risk factors onset, and progression of
      glaucoma (age, gender, intraocular pressure, refractive errors, circulation
      system disease, diabetes mellitus, vasospastic vascular disease) on FDT
      parameters. MATERIAL AND METHODS: Sixty four patients (128 eyes), in age between
      13-80, with refraction error from -14.5 to +6.5 D sph and average intraocular
      pressure 19.8 +/- SEM were included in this study. All patients were previously
      diagnosed towards glaucoma. The visual field testing with help of FDT Visual
      Field Instrument were made at least triple at all patients, with capitalize on
      the THR N-30 threshold program. Global indices: mean deviation (MD) and pattern
      standard deviation (PSD) and numerical value of mean retinal sensitivity for
      central visual field 5 degree sector (mean sensitivity to central 5 degrees--MS 5
      degrees) come in comparative analysis. All data were analyzed by chi2 and Kruskal
      Wallis tests. RESULTS: Comparative analysis examined groups of healthy persons,
      patients with glaucoma suspect and glaucoma, it proves statistically significant
      difference between MD, PSD and MS 5 degrees. Statistically no significant
      difference between PSD and MS 5 degrees at groups of healthy and glaucoma suspect
      patients was detected. In glaucoma group there did not reveal an influence on
      selected risk factors on FDT parameters. However, in glaucoma suspect group
      revealed an influence on most risk factors on perimetry parameters. CONCLUSIONS:
      FDT is useful for detection of glaucomatous nerve fiber damage. There should be
      taken precautions of interpretation FDT results at glaucoma suspect patients.

PMID- 15510507
TI  - [Short wavelength perimetry--the significance in diagnosis of glaucoma in myopic
      patients].
AB  - The static perimetry is the most useful diagnostic method in glaucoma. The aim of
      this paper is to compare the results of static short wavelength automatic
      perimetry (SWAP) with the classic one (white) in myopic patients with and without
      glaucoma. The Tubingen Automatic Perimeter was used, the threshold strategy
      within the central 30 degrees and glaucoma program was performed. The sensitivity
      of the retina in blue on yellow perimetry was nearly two classes lower than in
      the classic method in both groups. The enlargement of the blind spot and the
      appearance of the arcuate relative scotomas could be shown in SWAP, while classic
      perimetry is still normal. Both, the mean defect (MD) and the mean sensitivity
      (MS) in SWAP indicated for the very early glaucomatous changes in myopic patient,
      too. The changes of the loss variance (LV) was not characteristic for these
      patients.

PMID- 15510508
TI  - [Quantification of isopters using semiautomated kinetic perimetry (SKP) in
      glaucoma patients with advanced retinal nerve fiber layer (RNFL) loss].
AB  - PURPOSE: To quantify the area of isopters obtained using a new technique of
      kinetic visual field examination--semi-automated kinetic perimetry (SKP)--in case
      of advanced retinal nerve fiber layer (RNFL) loss, caused by glaucoma. MATERIAL
      AND METHODS: Forty-one subjects (19 men, 22 women; mean age 66.5 +/- 12.5 years)
      suffering from open-angle glaucoma (30 patients), normal tension glaucoma (5
      patients), juvenile glaucoma (2 patients) and PEX glaucoma (4 patients) were
      examined, using SKP program implemented in Octopus 101 instrument (Haag-Streit,
      Koeniz, Switzerland). One eye of each patient was tested using three stimuli
      according to the Goldmann classification. The stimuli III4e and I4e were
      obligatory. Additionally one stimulus (I3e or I2e) was used depending on the
      character of the defect. The stimulus angular velocity was kept constant at the
      level of 3 degrees/s. Obtained visual field (VF) results were classified
      according to the Aulhorn classification into stage III (26 VF) and IV (15 VF).
      The areas of isopters were measured in deg2. RESULTS: The mean area of isopter
      III4e was 9860 deg2, I4e--5171 deg2, I3e--1093 deg2, I2e--1093 deg2 in the group
      of Aulhorn stage III. In the group of Aulhorn stage IV the mean area of isopter
      III4e was 7488 deg2, I4e--3736 deg2, I3e--1109 deg2 and I2e--818 deg2. The mean
      test time was 16 min. (range 9-25 min.), 15.7 min. in the group of Aulhorn stage
      III and 16.5 min. in the group of Aulhorn stage IV, respectively. CONCLUSION: SKP
      seems to be an effective method for quantitative assessment and evaluation of
      isopter and scotoma areas (in deg2). In this study it was demonstrated that in
      case of more advanced stages of glaucomatous visual field loss (Aulhorn stage
      IV), the areas of isopters appeared to be smaller.

PMID- 15510509
TI  - [Comparison of SKP (semi-automated kinetic perimetry) and SASP (suprathreshold
      automated static perimetry) techniques in patients with advanced glaucoma].
AB  - PURPOSE: To compare the results of conventional suprathresold automated static
      perimetry (SASP) and a new method of kinetic visual field examination (semi
      automated kinetic perimetry--SKP) in patients with advanced retinal nerve fibre
      layer (RNFL) defects, caused by glaucoma. MATERIAL AND METHODS: Nineteen patients
      (10 women and 9 men) suffering from advanced open-angle glaucoma (17 patients)
      and low tension glaucoma (2 patients) were enrolled in this study. The mean age
      was 65.3 years (range 49.0-82.9 years). One eye of each subject was examined with
      SKP and SASP, both implemented in Octopus 101 perimeter (Haag-Streit, Koeniz,
      Switzerland) on the same day. The examiner using SKP did not know the SASP
      results. The static visual field examination was performed first. In order to
      compare visual fields results obtained with both methods, only central 30 degree
      area of the visual fields was taken into consideration. The area obtained by
      creating a virtual isopter (option of SKP software) located between the position
      of defective and intact visual field regions of SASP and the area of I4e isopter
      obtained with SKP (stimulus angular velocity 3 degrees/s) were measured in deg2
      and compared. RESULTS: The mean area (+/-SD) of I4e isopter obtained with SKP was
      1882 deg2 (+/- 510 deg2) and the mean area of SASP 30 degree visual field was
      1737 deg2 (+/- 546 deg2). This difference was not statistically significant.
      CONCLUSION: Quantitative comparison of static and kinetic perimetry is a
      difficult task to perform. The SKP software offers a possibility of direct
      quantitative assessment of the area of each isopters in deg2. This study shows
      that the results of visual field examinations obtained with both methods in this
      group do not differ significantly between SASP and SKP.

PMID- 15510510
TI  - [Central corneal thickness and intraocular pressure in the youth].
AB  - PURPOSE: To estimate the central corneal thickness in young patients and to
      evaluate the relationship between the intraocular pressure (IOP) and pachometry.
      PATIENTS AND METHODS: Eighty eyes of 40 children at the age from 9-18 years, mean
      13.75 were examined. The applanation tonometry, pachometry, refraction and
      examination of corneal diameter were done. To statistical purpose t-Student test
      was used alpha = 0.05. RESULTS: IOP ranged from 12 to 24 mmHg, in 32 eyes was
      above 17 mmHg, mean 20.2 +/- 1.46 mmHg (I group) and in 48 eyeballs ranged from
      12 to 17 mmHg, mean 15.6 +/- 0.96 mmHg (II group), p = 0. In the I group
      pachometry was from 480 to 591 microm, mean 542 +/- 11.1 and in the II group from
      451 to 570 microm mean 521.7 +/- 9.39 p = 0.006. Mean refractive error in the I
      group was -0.4 D (from -5.0 to +4.0 D) and in the II group mean -0.8 (from -6.25
      to +4.75), p = 0.45. In the both groups corneal diameter was from 11.5 to 12.5
      mm. Comparing eyeballs of patients at similar age, refraction and corneal
      diameter, it was shown that central corneal thickness in the group with higher
      IOP was statistically significantly bigger than in the group II. CONCLUSION:
      Measuring IOP in children we have to take into account the corneal thickness.

PMID- 15510511
TI  - [Central corneal thickness measurement in normal tension glaucoma].
AB  - PURPOSE: To evaluate corneal thickness in eyes with normal tension glaucoma.
      MATERIAL AND METHODS: CCT (measured by specular microscope Topcon SP2000P) was
      evaluated in 70 eyes of 39 patients with diagnosed NTG, 35 women and 4 men in age
      31-78 years (mean 68 years). RESULTS: Mean central corneal thickness measured by
      the specular microscope (between 11 and 1), was 523.7 microm in range 465-575
      microm. Impact of CCT on results of Goldman aplanation tonometry was detected in
      55.7% of NTG eyes--overestimated in 20% and underestimated in 35% of them.
      Corrected maximal IOP > 21 mmHg, was found in 14% of NTG eyes. CONCLUSIONS:
      Central corneal thickness measurement should be part of routine ophthalmological
      examination in glaucomatous patients (especially in NTG), being helpful in choice
      of optimal therapeutic strategy.

PMID- 15510512
TI  - [Changes in intraocular pressure during pregnancy].
AB  - PURPOSE: The purpose of this study was to define physiological changes in
      intraocular pressure during pregnancy. MATERIAL AND METHODS: 182 healthy pregnant
      women were examined cross-sectionally throughout the pregnancy. After measuring
      systolic and diastolic blood pressure full ophthalmological examination was
      performed (visual acuity, refractive error, intraocular pressure, slit lamp
      examination and fundus exam). All subjects were free from any systemic or ocular
      diseases. RESULTS: Intraocular pressure significantly decreased during successive
      stages of pregnancy. The results are presented as means SD. In the control group
      mean IOP was 15.6 +/- 1.81 mmHg. During first ten weeks of pregnancy mean IOP was
      15.33 +/- 1.98 mmHg, between 11-20 hbd was 14.52 +/- 2.37 mmHg, between 21-30 hbd
      was 13.47 +/- 2.19 mmHg, and towards the end of pregnancy (31-40 hbd) was 12.5 +/
      1.96 mmHg. The mean fall of IOP during whole pregnancy was 3.1 +/- 0.38 mmHg (p
      < 0.001). In these subjects pregnancy decreased IOP by 19.8%. CONCLUSIONS: The
      study results showed a gradual, statistically significant fall of intraocular
      pressure during pregnancy.

PMID- 15510513
TI  - [Timolol 0.5%/dorzolamide 2% fixed combination versus timolol 0.5%/pilocarpine 2%
      fixed combination in primary open-angle glaucoma or ocular hypertensive
      patients].
AB  - PURPOSE: To establish the efficacy and safety of timolol 0.5%/dorzolamide 2%
      fixed combination versus timolol 0.5%/pilocarpine 2% fixed combination, each
      given twice daily, in primary open-angle glaucoma and ocular hypertensive
      patients. MATERIAL AND METHODS: In this prospective, multicenter, double-masked
      trial, 37 patients were treated twice daily with timolol for 4 weeks. Then, they
      were randomized to one of the treatment medications for 6 weeks, after which they
      were treated with timolol again for 2 weeks before placed on the opposite
      treatment medication for 6 weeks. RESULTS: A total of 36 patients completed the
      trial. The mean baseline intraocular pressure (IOP) was 22.3 +/- 3.7 mmHg.
      Following 6 weeks of treatment, the mean decrease of IOP was 18.0 +/- 2.2 mmHg
      for timolol/dorzolamide combination and 17.4 +/- 2.0 for timolol/pilocarpine
      combination. The mean diurnal curve IOP was 18.1 +/- 2.2 mmHg for
      timolol/dorzolamide group and 16.7 +/- 1.9 mmHg for timolol/pilocarpine group.
      These differences were statistically significant. Statistically more patients
      reported ocular pain and diminished vision during use of the timolol/pilocarpine
      combination. CONCLUSIONS: This study suggest that timolol 0.5%/pilocarpine 2%
      fixed combination can provide at least similar efficacious reduction in IOP as
      timolol 0.5 %/dorzolamide 2% fixed combination in patients with primary open
      angle glaucoma and ocular hypertension.

PMID- 15510514
TI  - [The effectiveness of latanoprost for the treatment of pediatric glaucoma].
AB  - Latanoprost is a prostaglandin F2alpha analog that reduces intraocular pressure
      by 20-40% in adults with open-angle glaucoma. The efficacy and safety of this
      drug in children has not been widely reported. In our study we evaluated the
      effect of latanoprost in 14 children aged 12-18 years (mean 15 years): 10
      patients with glaucoma juvenile (I group); 2 patients with secondary glaucoma
      because of uveitis recidivans and 2 patients with aniridia and albinismus (II
      group). In the I group the average IOP decrement was 9 mmHg or 36.5% (range 29
      44%). In the II group the average IOP decrement was 6.5 mmHg or 23.5% (range 11
      33%). In one child with aniridia after one year of treatment IOL rose again to 26
      mmHg and antiglaucomatous surgery was necessary. Ocular side effects in children
      of latanoprost are mild.

PMID- 15510515
TI  - [Obstructive sleep apnea syndrome as a risk factor of glaucomatous neuropathy].
AB  - The consequences of sleep apneas in patients with obstructive sleep apnea (OSA)
      syndrome may influence the function of visual system. In 21 patients with OSA
      syndrome (apnea/hypopnea index--AHI 50+/-20) the detailed ophthalmologic studies,
      including tonometry, biomicroscopic evaluation of the anterior segment of the
      eye, automatic perimetry and stereoscopic examination of the eye fundus have been
      performed. In 4 patients (19%) the signs of lesions in the optic tract have been
      found. These were: defects in visual field caused by glaucoma (primary open-angle
      glaucoma and normal-tension glaucoma) in 2 patients and defects in visual field
      (concentric and quadrantic homonymous) caused by diffuse lesions in the cortico
      nuclear tract in 2 patients. In patients with the lesions in the optic tract
      there were severe disorders of breathing during sleep: AHI >60, mean SaO2 at the
      end of the apneas <86% and minimal SaO2 at the end of the apneas <70%. The
      authors conclude that in OSA patients there is a high risk of the lesions of the
      optic tract as a consequence of severe and repetitive hypoxemia during sleep.

PMID- 15510516
TI  - [Monitoring of blood pressure during phacotrabeculectomy].
AB  - PURPOSE: To evaluate systolic and diastolic blood pressure during
      phacotrabeculectomy performed under regional anaesthesia with retrobulbar block
      and intravenous analgosedation with midazolam and fentanyl. MATERIAL AND METHODS:
      68 patients were involved into the study: I Group: 37 patients with chronic
      cardiovascular and metabolic diseases: 22 women and 15 men (45 operations), mean
      aged 72.02 years, mean weight 73.4 kg, II Group: 31 patients without additional
      diseases: 20 women and 11 men (44 operations), mean aged 70 years, mean weight
      68.9 kg. Systolic and diastolic arterial blood pressure was recorded at 5-minute
      intervals throughout the intraoperative period and anesthetist intervened
      medically when necessary. RESULTS: In I Group statistically significant mean
      systolic BP decrease was observed in 5 and 20 minutes after injection of
      midazolam and fentanyl and mean diastolic BP decrease was observed in 5 and 15
      minutes after analgosedation. In II Group statistically significant mean systolic
      BP decrease was noted in 5 minutes and mean diastolic BP decrease in 5 and 35
      minutes. During phacotrabeculectomy mean systolic and diastolic BP was
      statistically higher in I group. In I group 12 patients and in II group 4
      patients required additional antihypertensive drug. CONCLUSIONS: Regional
      anaesthesia with retrobulbar block and intravenous analgosedation provides
      hemodynamic stability. Patients with cardiovascular and metabolic diseases
      required acute observation during phacotrabeculectomy.

PMID- 15510517
TI  - [Phacosclerectomy with acrylic implant--description of the method].
AB  - The surgical technique of deep sclerectomy with acrylic implant was described.
      The indications, advantages and possible complications of the method were
      presented.

PMID- 15510518
TI  - [Glaucoma and ocular ischemic syndrome--case report].
AB  - PURPOSE: Ocular ischemic syndrome (OIS) is often poorly diagnosed and treated as
      primary open angle glaucoma or later on, as neovascular glaucoma. We present a 54
      year old male, treated topical since 23 years for glaucoma and sent to our clinic
      for trabeculectomy because of rapid worsening of vision on right eye with
      bilateral total excavation of optic disc. MATERIAL AND METHODS: Observational
      case report. RESULTS: Because of typical signs of IOS (iris neovascularization,
      mid-peripheral dot and blot hemorrhages in both eyes, narrowed arterioles in
      right eye, following examinations were performed: Doppler ultrasonography of
      carotid arteries, digital subtractional angiography of the carotid vessels and
      magnetic resonance angiography. The examinations showed occlusion of the right
      common carotid artery and with 80% stenosis of the left common carotid artery,
      occlusion of abdominal aorta. After phacoemulsification with implantation of
      intraocular lens because of rapid intumescence cataract in the right eye, and
      endarterectomy of left external carotid artery, the neovascularization of the
      iris regressed in both eyes. CONCLUSION: In case of iris neovascularization or
      mid-peripheral hemorrhages the Doppler sonography of carotid arteries should be
      performed. Quick cooperation between ophthalmologist, radiologist and vascular
      surgeon following endarterectomy seems to stop progressing changes of ocular
      ischemic syndrome.

PMID- 15510519
TI  - [Malignant glaucoma following trabeculectomy--case report].
AB  - PURPOSE: Presentation of two cases of malignant glaucoma following filtration
      surgery. MATERIAL AND METHODS: Two patients with primary angle closure glaucoma
      has been treated with trabeculectomy. Flat anterior chamber, elevated IOP and the
      presence of patent irydectomy has been diagnosed 1 and 5 weeks after operation
      respectively. First patient in spite of peripheral irydectomy, medication and
      pars plana vitrectomy had high IOP and flat anterior chamber and has lost her
      sight. Second patient has improved after pharmacological treatment. CONCLUSIONS:
      Malignant glaucoma is a rare, but very serious complication after trabeculectomy.
      A very close and regular postoperative examination is necessary for a quick
      pharmacological or operative intervention.

PMID- 15510520
TI  - [Optic disc drusen and glaucoma--case report].
AB  - Optic disc drusen make examination towards glaucoma difficult to interpret. They
      change nerve head morphology and visual field defects can resembling glaucomatous
      damage. Patient with strong headache was examined and we found drusen on both
      optic nerve heads and intraocular pressure about 27 mmHg. Visual fields
      demonstrated scotomas--in lower half and the enlargement of the blind spot. After
      topical treatment and intraocular pressure normalization, the patient's
      complaints had gone. Control examination after one year revealed progression of
      visual field changes. Electrophysiological examination showed abnormalities
      typical for glaucoma.

PMID- 15510521
TI  - [The reasons for the false positive diagnosis of glaucoma].
AB  - Glaucoma, if left untreated, leads to blindness, but if detected early, disease
      progression can be stopped or slowed with drugs or surgical treatment. The
      development of existing and new diagnostic methods has allowed substantial
      improvement in the clinical detection of possible glaucoma. But in some cases
      false positive diagnoses can be undertaken. In this paper we discussed reasons
      for the wrong evaluation of factors suggesting the diagnosis of glaucoma, with
      special interest for mistakes in applanation tonometry results caused by thick
      cornea.

PMID- 15510522
TI  - [Laser therapy in the treatment of glaucoma].
AB  - PURPOSE: The paper is presenting the possibility of laser surgery in the
      treatment of glaucoma, new operations, and laser equipment. In the treatment of
      primary open angle glaucoma, argon laser was replaced by diode laser with
      continuous wave and in recent years by Nd:YAG Q switch, second harmonic 532 nm.
      This laser allows ophthalmologists for selective photoablation of cells with
      pigment in trabeculum without thermal effect. The introduction of fibers to
      transport energy let us increase accuracy and efficacy of laser therapy.
      Application of excimer lasers 308 nm enables to perform trabeculectomy by
      internal (ELT) and deep sclerectomy. After NPDS we sometimes have to use Q switch
      Nd:YAG for goniopuncture, to prolong filtration function of trabeculum--Descemet
      membrane. In primary angle closure glaucoma the most often laser treatment is
      iridotomy and gonioplasty. Laser cyclodestructive procedures almost completely
      eliminated cyclodiathermy and cyclokriotherapy, which were performed so far. The
      main cyclophotocoagulative procedures are contact transscleral
      cyclophotocogulation, transpupillary cyclophotocoagulation and intraocular
      cyclophotocoagulation. CONCLUSIONS: 1. The introduction of lasers enables safer,
      quicker and more effective antiglaucoma operations. 2. New laser equipment
      increases efficacy of so far performed laser surgery. 3. Laser surgery allows for
      the resignation of patients hospitalization and thereby enables to decrease the
      cost of treatment, and to increase the comfort of patients.

PMID- 15510523
TI  - [Pharmacological methods improving the effectiveness of filtering procedures].
AB  - Different antiproliferative agents: 5-fluorouracil, mitomycin C, growth factors
      antibodies, cyclosporine A, used as an adjunct to improve the success rate in
      filtering surgery and most common complications associated with them, are
      described.

PMID- 15510524
TI  - Ophthalmoscopic evaluation of the parapapillary region of the optic nerve head.

PMID- 15510525
TI  - Our profession is in good hands.

PMID- 15510526
TI  - Cholesterol and heart disease. Tips for you and your patients.

PMID- 15510527
TI  - Lowering high cholesterol. For your patients.

PMID- 15510528
TI  - Preconception to postpartum: management of pregnancy complicated by diabetes.

PMID- 15510529
TI  - Good oral health contributes to good total health: the role of the diabetes
      educator.

PMID- 15510530
TI  - Validation of a short dietary assessment questionnaire: the Rapid Eating and
      Activity Assessment for Participants short version (REAP-S).

PMID- 15510531
TI  - A nurse-coaching intervention for women with type 2 diabetes.
AB  - PURPOSE: The purpose of this pilot study was to determine the efficacy of a 6
      month nurse-coaching intervention that was provided after diabetes education for
      women with type 2 diabetes. METHODS: In this pilot study, 53 women were
      randomized to the nurse-coaching intervention or a standard care control
      condition. The nurse-coaching intervention consisted of 5 individualized sessions
      and 2 follow-up phone calls over 6 months. The nurse-coaching sessions included
      educational, behavioral, and affective strategies. Data were collected on
      physiologic adaptation (hemoglobin A1c [A1C] and body mass index [BMI]), self
      management (dietary and exercise), psychosocial adaptation (diabetes-related
      distress and integration), and treatment satisfaction at baseline, 3 months, and
      6 months. RESULTS: Women in the treatment group demonstrated better diet self
      management, less diabetes-related distress, better integration, and more
      satisfaction with care, and had trends of better exercise self-management and
      BMI. The A1C levels improved in both groups at 3 months, yet the difference
      between the groups was not significant. Attendance at nurse-coaching sessions was
      96%. CONCLUSIONS: This nurse-coaching intervention demonstrates promise as a
      means of improving self-management and psychosocial outcomes in women with type 2
      diabetes.

PMID- 15510532
TI  - Social cognitive theory in diabetes exercise research: an integrative literature
      review.
AB  - PURPOSE: This integrative review critically examined the literature on diabetes
      research using Social Cognitive Theory (SCT) to determine its predictive ability
      in explaining exercise behavior and to identify key interventions that enhance
      exercise initiation and maintenance. METHODS: Literature published between 1985
      and 2002 was searched using the following keywords: SCT, self-efficacy, diabetes
      mellitus, non-insulin-dependent diabetes mellitus, insulin-dependent diabetes
      mellitus, physical activity, and exercise. The databases searched were CINAHL,
      Medline, and PsychInfo. Of the 38 articles retrieved from databases, 13 were
      reviewed. RESULTS: A statistically significant relationship between self-efficacy
      and exercise behavior was found in correlational studies. Results from the
      predictive study support the predictability of self-efficacy for exercise
      behavior. Mixed results were found for the predictive ability of outcome
      expectancies for exercise behavior. Self-efficacy was predictive of exercise
      initiation and maintenance over time. The evidence for successful interventions
      to increase self-efficacy and exercise behavior over time was inconclusive.
      CONCLUSIONS: To better understand exercise behavior and to develop effective
      exercise interventions, a microanalytic, theory-driven approach to studying
      exercise behavior is needed. Several suggestions are offered to strengthen
      exercise self-efficacy.

PMID- 15510533
TI  - Contributions of children to the care of adults with diabetes.
AB  - PURPOSE: The purpose of this study was to determine the occurrence of child
      caregivers among adults with diabetes and the type of assistance they provide.
      METHODS: In this exploratory descriptive study, 51 diverse adults with diabetes
      from 9 clinics in 3 states completed a survey in English or Spanish about
      themselves and their child caregivers. Topics addressed in the survey were the
      duration and types of assistance, the children's education about diabetes, and
      the impact of children's caregiving on attendance at school and work. RESULTS:
      The occurrence of child caregiving for adults with diabetes was 15.7%, and
      greatest for Hispanics. Most adults and caregivers were female; 14 adults
      reported more than 1 child caregiver. The children ranged in age from 5 to 18
      years and began caregiving at a mean age of 11. Children provided from 1 to 10
      services, including planning meals, drawing up or administering medications,
      testing blood glucose, interpreting results, and transporting. Most children
      provided care several times a week, and nearly half had no education about
      diabetes care. CONCLUSIONS: Children of both sexes and 4 racial/ethnic groups
      provided a broad range of services to adults with diabetes with little
      preparation. Diabetes educators should consider if and how they can assess and
      include child caregivers in diabetes education.

PMID- 15510534
TI  - Online forum messages posted by adolescents with type 1 diabetes.
AB  - PURPOSE: Messages posted by adolescents with diabetes at public Web-based forums
      were assessed using content analysis. METHODS: Messages (n = 340) from
      adolescents self-identified as having diabetes were collected from public online
      discussion and question/answer forums and coded with respect to age, gender,
      duration of illness, and purpose of the post. Request messages were analyzed
      using a constant comparative method to generate descriptive categories.
      Nonparametric tests assessed for differences among groups and between forum types
      and request topics. RESULTS: Most messages were from females who more often
      posted at discussion forums. Males posted more information requests. Six
      categories emerged from the analysis: life tasks, social support, medical care,
      factual information, management, and intrapsychic. Social support messages
      accounted for half of discussion forum requests; information/management requests
      were common in question/answer forums. CONCLUSIONS: Data suggest that adolescents
      with diabetes visit online forums for social support, information, advice, and
      shared experience. Females used discussion forums more frequently and males
      requested more information.

PMID- 15510535
TI  - Seasonality of birth and conception to teenagers in Texas.
AB  - We study the births to teenagers during the years 1964-2000 and analyze
      separately the three main racial/ethnic groups in Texas (White, Hispanic, and
      African American), as well as married and unmarried teens during the years 1994
      2000. By using traditional statistical methods of analysis and a filter based on
      the multiresolution wavelet analysis, we draw inferences about the times of the
      year when adolescent females of different racial/ethnic and marital groups have
      the highest probability for pregnancy ending in live birth. Multiple factors
      influencing teen pregnancy are identified and associated with temporal features
      of social, cultural, educational, and familial processes. In particular, we
      detect links between unmarried teen conception times and school terms, and weekly
      birth patterns associated with scheduled c-sections that differ according to
      racial/ethnic groups.

PMID- 15510536
TI  - The influence of latitude and cloud cover on the seasonality of human births.
AB  - BACKGROUND: A previous study (Cummings, 2002), hypothesized that human birth
      seasonality was primarily related to environmental light intensity/photoperiod.
      PURPOSE: There are two primary goals: to explain seasonality differences between
      U.S., Canada, and Europe and to test the influence of environmental light
      intensity/photoperiod at divergent latitudes. METHODOLOGY: Existing seasonality
      data were extracted from previous studies at various locations throughout the
      world. Daily cloud cover amounts (clearness) were utilized as indices for
      environmental light intensity. DISCUSSION: Results were evaluated and discussed
      for each sub-study. CONCLUSION: Sub-study results support the hypothesis that
      human birth seasonality may be influenced by environmental light intensity and
      photoperiod. This conclusion is supported by logical links between increased
      light intensity/photoperiod and conceptions at different latitudes. Irrefutable
      proof may involve correlating long term changes in cloud cover with long term
      changes in human birth seasonality.

PMID- 15510537
TI  - The father(to)child affiliative bond: convergent evolution with the canid
      analogue.
AB  - Primate homologues, especially from the African great apes, can usually be
      successfully utilized to form comparisons with the human condition. However, the
      man(to)child pair-bond is not paralleled by any terrestrial primate nor even many
      mammals. Hence, knowledge of primate behavior would not be predictive of the pan
      human social father. It is suggested that female choices of mating partners
      shifted in the direction of a canid analogue in that men's motivations to share
      resources with the female and to exhibit paternalistic behaviors were positively
      selected. Accordingly, it is argued that, for humans, convergent evolution
      occurred which trended toward the canid template. Consequently, it would be
      predicted that, compared to other terrestrial primates, the neuro-hormonal basis
      for the mother-child affiliative bond would be similar, but the basis for
      man(to)child affiliative bond would be dissimilar.

PMID- 15510538
TI  - Double impact: what sibling data can tell us about the long-term negative effects
      of parental divorce.
AB  - Most prior research on the adverse consequences of parental divorce has analyzed
      only one child per family. As a result, it is not known whether the same divorce
      affects siblings differently. We address this issue by analyzing paired sibling
      data from the 1994 General Social Survey (GSS) and 1994 Survey of American
      Families (SAF). Both seemingly unrelated regressions and random effects models
      are used to study the effect of family background on offspring's educational
      attainment and marital stability. Parental divorce adversely affects the
      educational attainment and the probability of divorce of both children within a
      sibship; in other words, siblings tend to experience the same divorce the same
      way. However, family structure of origin only accounts for a trivial portion of
      the shared variance in offspring's educational attainment and marital stability,
      so parental divorce is only one of many factors determining how offspring fare.
      These findings were unchanged when controlling for a number of differences both
      between and within sibships. Also, the negative effects of parental divorce
      largely do not vary according to respondent characteristics.

PMID- 15510539
TI  - Human ecology, crime, and crime control: linking individual behavior and
      aggregate crime.
AB  - The paper extends previous research published by Cohen, Machalek, Vila, and
      others on the evolutionary-ecological paradigm for understanding criminal
      behavior. After reviewing literature related to human ecology and crime, the
      paper focuses on elements relevant to human ecology-biology, development, and
      ecological factors--and their role in criminal behavior. Major emphasis is placed
      on the linkages between individual factors and macro-level crime using chronic
      offending as a case in point. The principles of evolutionary ecology then are
      used to discuss counterstrategies to crime, and the prospects for
      protection/avoidance, deterrent, and nurturant strategies in light of evidence on
      chronic offending.

PMID- 15510540
TI  - Economic distress and cause-of-death patterns for black and non-black men in
      Chicago: reconsidering the relevance of classic epidemiological transition
      theory.
AB  - The mortality disadvantage of African Americans is well documented, but previous
      studies have not considered its implications for population theory in the general
      case of industrialized nation states with high levels of income inequality. This
      paper examines the relevance of classic epidemiological theory to the extremes of
      income and mortality observed in Chicago, one of America's most racially divided
      cities. We analyze cause-specific death rates for black and non-black male
      populations residing in Chicago's community areas by using linked data from the
      1990 Census and from 1989-1991 individual death certificates. The same cause-of
      death patterns explain much of the mortality of black and non-black men. These
      two major structures include one, degenerative diseases, the other, "tough
      living" causes (accidents, homicides, and liver disease). Community socioeconomic
      status is strongly related to tough-living deaths within each racial group, and
      to degenerative deaths for African Americans. Black men's tough-living mortality
      is much greater than non-blacks', but their younger age structure suppresses
      their degenerative death rates. Aggregate unemployment and social disorganization
      account for the most salient disparities in mortality across racial groups. This
      patterning of mortality along a socioeconomic continuum supports epidemiological
      theory and extends its applicability to highly unequal populations within
      industrialized countries.

PMID- 15510541
TI  - Reconciling heart disease mortality and ICD codes.
AB  - This study uses 61 years of death certificates for Bexar County, Texas, uniformly
      coded under ICD 9, to describe the transition in heart disease mortality from
      1935-1995. We find that life expectancy for persons dying with heart diseases
      increased throughout this period, with clear differences in rates of increase for
      males and females, associated with acute ischemic heart disease. Our data point
      to an epidemic of AIHD in the 1950s and 1960s, which is now abating. Findings are
      less clear for chronic ischemic heart disease, while other major heart diseases
      cannot be traced with any confidence owing to changes over time in the emphasis
      accorded particular causes. Our findings suggest caution with respect to the
      socioeconomic analysis of heart disease mortality data, particularly where the
      instability of the coding conventions has been most acute.

PMID- 15510542
TI  - Infant mortality in Zambia: socioeconomic and demographic correlates.
AB  - Trends in infant mortality in Zambia suggest a reversal of the decline
      experienced between the 1960s and the late 1970s. From a high of about 140,
      infant mortality rate declined to about 90 in the late 1970s only to rise again
      to 100 by 1996. Data on 5,600 births born between 1987 and 1992, and 6,630 births
      between 1991 and 1996 from the Zambian DHS are analyzed to identify socioeconomic
      and demographic correlates of infant mortality. Demographic factors such as small
      size at birth and short birth intervals are associated with higher neonatal
      mortality. In the post-neonatal period, urban children from poorer households had
      the highest mortality between 1991-1996. Also, differences in infant mortality
      rates between provinces narrowed. Children born in the most developed province of
      Lusaka had as high of risk of dying as those from Luapula, a province with a
      history of extremely high mortality rates in Zambia.

PMID- 15510543
TI  - The relationships among measures of egg albumen height, pH, and whipping volume.
AB  - A total of 2123 eggs obtained from Brown Leghorn hens (unselected since 1965, ISA
      Brown, commercial brown egg layer) and Babcock hens (commercial white egg layer)
      at 32, 50, and 68 wk of age were used to investigate relationships among measures
      of albumen quality and a functional property of albumen. The eggs were sampled
      fresh and after storage for 5 and 10 d. At sampling, eggs were weighed and
      broken, and albumen height, pH, and volume after whipping for 80 s were measured.
      Also, yolks were weighed, dried shells were weighed, and albumen weight was
      determined by difference. Egg weight and the weights of the 3 principal
      components of the egg all increased with increasing age of the hen, with yolk
      weights increasing proportionately more. With storage, egg and albumen weights
      decreased, whereas yolk weight increased. Eggs from Brown Leghorn hens were
      smallest but had proportionately the largest yolks. Albumen height decreased with
      time in storage, and albumen pH and whipping volume increased. Differences
      between lines suggested that selection has changed the proportion of the yolk,
      albumen, and shell and has increased albumen height. Albumen height and whipping
      volume were negatively correlated, and differences between lines suggest that
      selection could have decreased the foaming ability of albumen, a principal reason
      for including eggs in many processed food products.

PMID- 15510544
TI  - The effects of different beak trimming techniques on plasma corticosterone and
      performance criteria in Single Comb White Leghorn hens.
AB  - DeKalb XL chicks were given a beak trim at 6 d of age (6DP) with a 2.8-mm gauge
      and a beak trim at 11 wk (11WB) with a block cut approximately 2 mm anterior to
      the nasal openings. Corticosterone (CS) levels of the 6DP treatment were (P < or
      = 0.01) elevated above nontrimmed CS levels at 2 h posttrim; and BW and feed
      consumption (FC) of the 6DP were depressed until 8 wk of age. At 11 wk of age, CS
      of the 11WB treatment was (P < or = 0.02) elevated above controls at 1, 2, 8, and
      5 wk posttrim. The 11WB treatment resulted in a decrease in FC and a reduction in
      BW at 12, 14, and 16 wk of age, whereas there were no differences among
      treatments in livability during the pullet phase. At 72 wk of age, FC of the
      nontrimmed controls was greater than both beak trimmed treatments, and both beak
      trimmed treatments had greater hen housed eggs, percentage hen day egg
      production, and percentage livability. Both beak trimmed treatments resulted in
      better egg income, feed cost per hen, and net income (NI). The 6DP and 11WB beak
      trim treatments resulted in an improvement of NI per hen of 1.48 dollars and 1.86
      dollars, respectively. In addition, both beak trimmed treatments exhibited better
      feather score and Hansen's test (fearfulness). It was concluded that pullets and
      hens could adapt to the physiological stress of beak trimming and out perform,
      during a lay phase, controls whose beaks were not trimmed.

PMID- 15510545
TI  - A mathematical model of the population dynamics of Heterakis gallinarum in
      turkeys (Meleagridis gallopavo).
AB  - Heterakis gallinarum is a relatively nonpathogenic organism, but it is important
      as the transport host for the pathogenic protozoan Histomonas meleagridis. A
      mathematical model was developed to describe the population dynamics of Heterakis
      gallinarum in a turkey flock to study its kinetics in a number of hosts. The
      model includes quantitative (parasite burden) and qualitative (number of hosts
      without mature parasite) descriptions of these dynamics. To understand the role
      of Heterakis as a transport host, the various elements that delay the beginning
      of development of the parasite population (e.g., necessary delay of larval stage,
      the probability of having a male and female in the same host) were taken into
      account. From published data, the negative binomial distribution parameter k =
      0.24, which described the aggregated distribution of the Heterakis among the
      hosts, was calculated. The sensibility study showed that when the k parameter
      decreased (i.e., when the population was more aggregated), infestation increased
      quantitatively (mean parasite burden increased) but not qualitatively (the number
      of host without mature parasite increased). The model demonstrated that the
      population dynamics of Heterakis takes time; for instance, with an aggregated
      population of Heterakis at d 90, the host is mainly free of adult parasite. These
      results may be used in the future to test the role of Heterakis in the spread of
      Histomonas.

PMID- 15510546
TI  - Surface disinfection tests with Salmonella and a putative indicator bacterium,
      mimicking worst-case scenarios in poultry houses.
AB  - Surface disinfection studies mimicking worst-case scenarios in badly cleaned
      poultry houses were made with 3 bacterial isolates (Salmonella enteritidis,
      Salmonella senftenberg, and Enterococcus faecalis), and 3 1% disinfectant
      solutions, formaldehyde (F; 24.5% vol/vol), glutaraldehyde/benzalkonium chloride
      (G; Bio Komplet Plus), and a peroxygen compound (P; Virkon S), with World Health
      Organization (WHO) standard hard water as a control. Materials (concrete paving
      stones, steel feed chain links, wooden dowels, and jute egg belts) and organic
      matter found commonly in poultry houses (feed, fats, egg yolk) were used in the
      tests. Organic matter inoculated with high numbers of stationary phase cultures
      was added to materials and dried for 24 h at different temperatures (6, 11, 20,
      or 30 degrees C), immersed in solutions for set time periods (5, 15, or 30 min),
      and dried again for 25 h (6, 11, or 30 degrees C). Then, traditional recovery
      procedures (using 10-fold dilutions until 10(-4), i.e., a most probable number
      method) were applied. For the 2 Salmonella isolates, the efficacy of the
      solutions was (in decreasing order): formaldehyde > glutaraldehyde/benzalkonium
      chloride > peroxygen compound > WHO hard water, except when feed chain links with
      fats were disinfected using 30 degrees C before and after disinfection, for which
      the peroxygen compound seemed more effective. Enterococcus faecalis was equally
      or less susceptible than S. enteritidis and S. senftenberg, indicating its
      suitability as an indicator bacterium. For the peroxygen compound, S. senftenberg
      was more susceptible than S. enteritidis in spite of higher minimum inhibitory
      concentrations to this disinfectant for the former.

PMID- 15510547
TI  - Effect of duration of cold stress on plasma adrenal and thyroid hormone levels
      and immune responses in chicken lines divergently selected for antibody
      responses.
AB  - There is increasing evidence that stress affects various immune processes. Some
      of these changes are due to hormonal changes involving corticosterone (CORT),
      triiodothyronine (T3), and thyroxine (T4). Effects of stress depend on the nature
      of specific stressors (e.g., thermal extremes, diet, pollutants), and stress
      modifiers (e.g., genetic make-up, duration and severity of the stressors). We
      studied the effects of a specific stress (cold stress) with stress-modifiers
      (duration of stress and genotype of the bird) on immune responses and plasma
      adrenal and thyroid hormone levels in 3 layer-type chicken lines. Two lines were
      divergently selected for high (H line) or low (L line) antibody responses to
      SRBC, and the third line was a randombred control (C) line. Growing chicks (3- to
      4-wk-old) of the 3 lines were feed-restricted at 80% of ad libitum consumption,
      and subjected to cold stress (CS) at 10 degrees C continuously for 7, 5, 3, 1, or
      0 d before immunization with keyhole limpet hemocyanin (KLH). Specific antibody
      titers to KLH, and in vitro lymphocyte proliferation (LP) upon mitogen
      stimulation were measured. In addition, adrenal and thyroid hormone levels were
      measured in the plasma samples collected at the end of CS. No significant effect
      of duration of CS on specific antibody titers was found in the 3 lines. A
      significant enhancing effect of CS was found on LP. A significant dose-dependent
      suppressive effect of CS was found on plasma CORT levels. One day of CS had a
      significant enhancing effect on T3 levels. There was no significant effect of
      duration of CS on T4 levels. We conclude that CS does not affect specific
      antibody responses, but may have a modulating effect on cellular immunity and
      plasma CORT levels, depending on the duration of the stress. The present study
      suggests an inverse relationship between LP and CORT. This is the first study
      that reveals an absence of significant differences in adrenal and thyroid hormone
      levels in the described selection lines.

PMID- 15510548
TI  - Atmospheric ammonia is detrimental to the performance of modern commercial
      broilers.
AB  - Atmospheric ammonia inhibits broiler performance. Quantified effects are based on
      older genetic stock with a BW of 2000 g at 7 wk. In contrast, modern genetic
      stock reaches 3200 g at 7 wk of age. To assess the impact on present day
      broilers, 2 trials were conducted exposing male broilers to graded levels (0, 25,
      50, and 75 ppm) of aerial ammonia from 0 to 4 wk of age. Sixty, 1-d-old chicks
      were placed in environmentally controlled chambers, weighed weekly as a group,
      and processed with yield determined at 7 wk of age. Final BW was significantly
      depressed by 6 and 9% for the 50 and 75 ppm concentrations of ammonia as compared
      with 0 ppm. Also, mortality was significantly greater at the 75 ppm ammonia
      concentration, 13.9% compared with 5.8% for the 0 ppm treatment. Percentage yield
      of deboned meat per bird decreased slightly with increasing exposure to ammonia
      but was not statistically significant. Although current genetic stock reaches
      growout weights that are approximately 60% greater than those 2 decades ago, the
      relative quantified effects of ammonia exposure were similar. Additionally,
      statistical analysis of the results provided a simple equation, presented herein,
      for predicting the decline in BW of male broilers after exposure to ammonia.

PMID- 15510549
TI  - Impact of dietary supplemental methionine sources on sensory measurement of odor
      related compounds in broiler excreta.
AB  - An experiment was conducted to detect differences in odor characteristics of
      broiler excreta due to utilization of different supplementary Met sources by a
      trained human descriptive aroma attribute sensory panel. The 5 treatment groups
      were no supplemental Met (control group), sodium methioninate aqueous solution,
      dry Met hydroxy analogue, liquid Met hydroxy analogue, and DL-Met. Two trials
      were conducted consisting of 5 treatment groups with 3 replications of 13
      randomly distributed straight run broiler chicks per pen reared in battery cages.
      Starter and grower diets were formulated to contain 0.5 and 0.38% Met activity,
      respectively (except control group, 0.35% Met activity). Excreta were collected
      for 24 h in litter pans lined with aluminum foil at wk 4, 5, and 6 and analyzed
      by a trained sensory panel (7 people). Each panelist was given 25 g of manure
      heated at 27 degrees C for 5 min for sensory analysis. The 13 odor attributes
      used to determine differences in broiler excreta by the trained sensory panel
      were ammonia, dirty socks, wet poultry, fermented rotten fruit, hay, musty wet,
      sharp, sour, urinous, rotten eggs, irritating, pungent, and nauseating. Panelist
      marked intensities for each attribute ranging from 0 = none and 15 = extremely
      intense. Each panelist was given 2 replications of each treatment group in a
      random order each week (total of 10 samples per wk). All data were evaluated by
      ANOVA using the general linear model procedure of SAS software. No significant
      differences were observed in BW, feed consumption, or feed conversion among the
      treatments. The attributes of ammonia, wet poultry, rotten fruit, musty wet,
      sharp, and pungent differed (P < 0.05) across treatment groups. These findings
      demonstrate that supplemental Met sources significantly influence odor production
      in broiler excreta.

PMID- 15510550
TI  - Research note: Effects of different bone preparation methods (fresh, dry, and fat
      free dry) on bone parameters and the correlations between bone breaking strength
      and the other bone parameters.
AB  - A study was conducted to evaluate effects of different bone preparation methods
      on bone parameters and the correlations between bone breaking strength and the
      other bone parameters. Bone breaking strength is dramatically changed depending
      on bone preparation methods, whereas other bone parameters such as ash content
      and ash concentration are not significantly influenced by bone preparation
      methods. Thus, the objective of this study was to evaluate the effects of 3 bone
      preparations (fresh, dry, and fat-free dry) on bone parameters and the
      relationship between bone breaking strength and bone parameters. Sixty Single
      Comb White Leghorn hens were used for this study. Hens were euthanized by CO2
      gas, and the right tibia and femur were collected. The bones were divided into 3
      treatment groups: fresh, dry, and fat-free dry. There were no significant
      differences in fresh weight, bone volume, dried weight, ash weight, and ash
      concentration of tibia and femur among the treatments. However, fresh tibia
      (24.13 kg) exhibited more bone breaking strength compared with the dried (9.90
      kg) and fat-free dried bones (7.41 kg) (P < 0.05). The bone breaking strength
      (20.97 kg) of fresh femur was also significantly higher than the dried (9.22 kg)
      and fat-free dried femurs (6.94 kg). The bone breaking strength of the fresh bone
      was highly correlated with dried weight, ash weight, and ash concentration,
      whereas that of the fat-free dried bone was poorly correlated with the other bone
      parameters. The results indicate that fresh bone gives better bone breaking
      strength correlated to the other bone parameters than dry or fat-free dry
      preparation.

PMID- 15510551
TI  - Intestinal mucosal mast cell immune response and pathogenesis of two Eimeria
      acervulina isolates in broiler chickens.
AB  - Four experiments were conducted comparing intestinal immune responses to 2
      isolates of Eimeria acervulina (EA), EA1 and EA2. In experiments 1 and 2, broiler
      chicks of 2 commercial breeds were divided into control (nonchallenged), EA1-, or
      EA2-challenged groups. On d 6 postchallenge (PC), changes in BW were determined,
      intestinal lesions were scored, and duodenal tissue was evaluated for
      morphometric alterations and mucosal mast cell numbers. EA1 produced classical
      duodenal lesions and reduced villus height to crypt depth ratios compared with
      controls; however, no differences were found in mast cell counts. EA2 produced
      different results, and observed data were suggestive of an anaphylactic-like
      intestinal secretory response compared with EA1 or controls. In experiment 3,
      tissues were analyzed from d 2 through 6 PC. Villus atrophy and crypt hyperplasia
      were increased on d 5 PC in both challenged groups. Mast cell counts were
      significantly greater on d 3 and 4 PC in EA1-challenged birds. In experiment 4,
      EA2 oocysts were cleaned with 5.25% sodium hypochlorite to evaluate the
      possibility of a bacterial contaminant contributing to the pathogenesis of
      intestinal alterations. No evidence of a bacterial contaminant contributing to
      the pathology was observed. These data are indicative of differential host
      response and immunovariability between different isolates of the same Eimeria
      species in 2 breeds of commercial broiler chickens.

PMID- 15510552
TI  - Differences in intestinal gene expression profiles in broiler lines varying in
      susceptibility to malabsorption syndrome.
AB  - Examination of the host gene expression response upon encounters with pathogens
      may provide insights into the cellular events following an infection. In
      addition, it may shed light on the basic mechanisms underlying differences in the
      susceptibility of the host. In this study gene expression in the chicken jejunum
      was investigated in 2 different broiler lines under control and malabsorption
      syndrome (MAS) affected conditions. The 2 broiler lines differ in their
      susceptibility for MAS. The gene expression was investigated at 6 different times
      postinoculation using a custom-made intestine specific cDNA microarray. More than
      70 up- or downregulated genes were identified after a MAS inoculation in both
      broiler lines. However, the number of the up- and downregulated genes varied
      between the 2 lines, with more differences in expression in the most susceptible
      line. Marked differences were observed in expression profiles between the 2
      broiler lines, in control as well as in the MAS affected birds. The microarray
      data were validated and confirmed by quantitative real time PCR. The
      differentially expressed genes included immune related genes, genes associated
      with food absorption, and genes that need to be characterized further before
      their role in MAS and MAS susceptibility can be understood.

PMID- 15510553
TI  - Impact of spray-dried bovine serum and environment on turkey performance.
AB  - Two 28-d experiments were conducted with 280 and 224 Hybrid turkeys for
      experiments 1 (7 poults per pen, 10 pens per treatment) and 2 (7 poults per pen,
      8 pens per treatment), respectively. The effect of Innavax (INX; spray-dried
      serum) administered in drinking water on turkey performance was evaluated. In
      both experiments, turkeys were randomly assigned to receive tap water mixed with
      0, 0.45, 0.90, or 1.35% (wt/wt) INX and housed in floor pens containing clean
      (experiment 1) or used (experiment 2) litter. In experiment 1, a quadratic
      response in average daily gain (ADG), water intake, and feed efficiency occurred
      (P < 0.05) in the first week with increasing levels of INX. During the second and
      third weeks, a quadratic response in water intake occurred (P < 0.05) with 0.90%
      INX resulting in peak intake. In the fourth week, ADG increased quadratically (P
      < 0.05) with increasing INX. Overall for the 4-wk period, ADG and water intake
      increased quadratic manner (P < 0.05) with increasing INX to a maximum at 0.90%.
      In experiment 2, ADG and water intake increased linearly (P < 0.05) during the
      first week. Feed efficiency was unaffected (P > 0.05) by experimental treatment
      during the first week but increased linearly (P < 0.05) from d 8 to 14 and d 15
      to 21. The growth response to INX was influenced by environment. A greater growth
      response of turkeys to INX was observed when turkeys were housed in floor pens
      with used litter compared with floor pens with clean litter.

PMID- 15510554
TI  - Effects of dietary conjugated linoleic acid on the productivity of laying hens
      and egg quality during refrigerated storage.
AB  - Five hundred and four 40-wk-old Brown Dwarf hens (1.51 +/- 0.08 kg BW) were fed
      corn-soybean meal diets containing 0, 1, 2, 3, 4, 5, or 6% conjugated linoleic
      acid (CLA) for 56 d to measure the effects of dietary CLA on laying hen
      productivity and egg quality during refrigerated storage. Four hens were placed
      in 1 cage, and 3 cages were grouped as 1 replicate resulting in 6 replicates per
      treatment. After feeding the experimental diets for 11 d, eggs were collected to
      determine the fatty acid composition of egg yolks. From d 12 to 18, eggs from
      hens fed diets containing 0, 2, 4, and 6% CLA diets were stored at 4 degrees C
      for up to 28 d. At designated times (1, 14, or 28 d), eggs were taken, broken,
      and shelled to evaluate water content, pH, and ion concentration. Firmness of
      hard-cooked egg yolk was also determined. With increased dietary CLA, feed
      intake, BW gain, rate of egg production, egg weight, and feed efficiency all
      decreased linearly (P < 0.01). The weight of the yolk, albumen, and shell
      decreased linearly (P < 0.01) with increasing dietary CLA. Concentration of CLA
      in the yolk lipids increased quadratically (P < 0.01), with increasing dietary
      CLA. Concurrent increases (P < 0.01) in the concentration of myristic, palmitic,
      and stearic acids and decreases (P < 0.01) in oleic, linoleic, linolenic, and
      archidonic acids in egg yolk lipids were observed. Days of storage and CLA (P <
      0.01) increased yolk firmness. Egg yolk water content and pH increased with
      storage and CLA content (P < 0.01). Corresponding decreases were observed in
      albumen pH. Regardless of dietary treatment, the concentrations of Na, K, and Mg
      in egg yolks increased with longer storage time. At 28 d of storage, there was a
      linear (P < 0.01) increase in Na, K, and Mg content in egg yolks as dietary CLA
      increased. In contrast to the egg yolk, the concentrations of Na, K, and Mg in
      egg albumen decreased with storage time. On d 28, there was a linear decrease (P
      < 0.01) in the Na content of albumen with increasing CLA. This study suggests
      that the greater firmness of CLA-fed eggs might be related to the change of pH,
      water content, and ion concentrations during refrigerated storage.

PMID- 15510555
TI  - Real-time PCR detection of lactic acid bacteria in cecal contents of eimeria
      tenella-lnfected broilers fed soybean oligosaccharides and soluble soybean
      polysaccharides.
AB  - This experiment was conducted to test whether dietary soybean meal
      oligosaccharides (SMO) and water-soluble polysaccharides (SMP) can assist broiler
      chickens in resisting Eimeria tenella, and to determine the survival of lactic
      acid bacteria in cecal contents postinfection. All birds received a soybean meal
      free diet. The 6 experimental treatments were as follows: positive (COR) and
      negative (COW) control groups, 2 groups fed diets containing either 1% SMO or
      0.5% SMP from 1 to 11 d of age; a vaccinated group (VAC), and an anticoccidial
      medicated group (ANT). Chickens of all treatments except COW were orally infected
      with 1000 sporulated oocysts of E. tenella on d 15. Fecal oocyst shedding was
      monitored per treatment group between d 5 and 13 postinfection. Lactic acid
      bacteria (LAB) in cecal contents were evaluated by a real-time PCR technique on d
      7 postinfection. The results showed that the SMO and SMP groups had a lower
      number of oocysts per gram of feces during the monitoring period than the COR
      group. Threshold cycles were 22.21, 27.68, 13.99, 14.92, 12.97, and 14.85, for
      COW, COR, SMO, SMP, VAC, and ANT groups, respectively; specific PCR products were
      confirmed by the results of melting curve analysis and agarose gel
      electrophoresis. The results suggest that these LAB communities were promoted by
      SMO and SMP and have a competitive exclusion function when broiler chickens are
      infected with E. tenella.

PMID- 15510556
TI  - Interrelationship between methionine and cystine of early Peking ducklings.
AB  - A 4 x 5 factorial experiment containing 4 cystine levels (0.325, 0.406, 0.487, or
      0.568%) and 5 methionine levels (0.285, 0.385, 0.485, 0.585, or 0.685%) was
      conducted to evaluate the interrelationship between methionine and cystine in
      corn-peanut meal diet for Peking ducklings from hatch to 21 d of age. Eight
      hundred 1-d-old male white Peking ducklings were assigned to 20 experimental
      treatments. All treatments were replicated 4 times using 10 ducklings per pen. As
      dietary methionine level increased, weight gain and feed intake increased and
      then decreased; the quadratic response of weight gain was significant (P < 0.05).
      The methionine requirement for maximum efficiency of feed utilization (0.585%)
      was higher than for maximum weight gain (0.485%). According to the quadratic
      model, the optimal methionine requirement of Peking ducklings from hatch to 21 d
      of age was 0.481% (95% of the level at maximum response). The plasma uric acid
      concentration was very low (P < 0.05) when dietary methionine was 0.485%. When
      dietary methionine was excessive (0.685%), the plasma homocysteine concentration
      increased (P < 0.05). On the other hand, the cystine requirement of ducklings
      from hatch to 21 d of age was not more than 0.325%. A high level of cystine
      (0.568%) depressed weight gain and feed intake (P < 0.05), but cystine
      supplementation in the diets lowered the plasma homocysteine concentration (P <
      0.05). There were no significant interactions between methionine and cystine on
      growth performance, plasma uric acid, and plasma homocysteine.

PMID- 15510557
TI  - Enrichment of eggs with lutein.
AB  - Lutein is being considered as a nutrient for prevention of macular degeneration
      in the aging population. Two experiments were designed to study the transfer
      efficiency of lutein from the layers' diet into the egg. In experiment 1, laying
      hens were fed corn-soy diets supplemented with 0, 125, 250, 375, 500, 625, 750,
      or 1000 ppm of lutein. After 30 d, eggs were collected and assayed for lutein. In
      a second study, layers were fed corn-soy diets or diets containing corn gluten
      meal and alfalfa, with or without added flaxseed. Diets in experiment 2 were
      supplemented with 0, 125, 250, or 500 ppm of lutein. Adding lutein to the layers'
      diet resulted in a significant (P < 0.01) increase in Roche color score of yolk
      within 7 d of supplementation. In experiment 1, lutein was transferred into the
      yolk (P < 0.01) increasing from a basal level of 0.3 mg to 1.5 mg/60 g of egg.
      However, there was no significant (P > 0.05) increase in yolk lutein with diet
      supplements >375 ppm. In the second experiment, using corn gluten meal and
      alfalfa further increased lutein content that leveled off at 2.2 mg/60 g of egg
      with a diet supplement of 500 ppm of lutein. Adding flax to these diets seemed to
      depress yolk lutein content. Yolk lutein content can be increased, although
      further studies are needed to investigate the major decline in transfer
      efficiency seen with higher levels of dietary supplementation.

PMID- 15510558
TI  - Effect of dietary crude protein and lysine on feather growth in chicks to twenty
      one days of age.
AB  - A study was conducted to evaluate feather development in male broiler chickens
      fed variable levels of dietary CP and lysine. Diets contained 170, 210, 250, or
      290 g of CP/kg with 0.86, 1.22, 1.34, or 1.46% lysine, each being fed to 2
      replicate groups of 4 chicks. Dietary CP per se had a significant effect on
      feather weight and feather nitrogen gain. Increasing dietary CP from 170 to 250 g
      of CP/kg of diet increased feather weight and feather nitrogen gain. No
      differences were found at higher dietary CP levels. Dietary lysine levels from
      0.86 to 1.46% did not affect feather weight, feather nitrogen gain, or
      feather:body weight in male chicks to 21 d. However, feather weight and feather
      nitrogen gain decreased as lysine increased in diets with 170 and 210 g of CP but
      not with 250 or 290 g of CP/kg. Percentage of total feather nitrogen was also
      influenced by the level of dietary lysine in diets containing 210 and 250 g of
      CP/kg. Feather development was more influenced by dietary CP per se than by
      levels of lysine.

PMID- 15510559
TI  - The effect of fat type, carbohydrase, and lipase addition on growth performance
      and nutrient utilization of young broilers fed wheat-based diets.
AB  - A 2 x 2 x 2 factorial experiment was conducted to evaluate the effects of fat
      type (beef tallow [50 g/kg diet] or canola oil [50 g/kg of diet]), carbohydrase
      addition (none or carbohydrases [0.4 g/kg diet]), and lipase addition (none or
      lipase [0.2 g/kg of diet]) on growth performance and nutrient utilization of male
      broilers fed a wheat-based diet from 5 to 18 d. The carbohydrase supplement
      contained xylanase, glucanase, cellulase, and other enzyme activities. The
      experimental diets were formulated to be suboptimal in major nutrients and each
      was fed in a mash form to 10 replicate pens of 5 broilers per pen. Body weight
      gain was not affected by fat type but a poorer feed/gain ratio (P < 0.001) was
      noted for tallow-containing diets. Regardless of fat type, carbohydrase enzyme
      supplementation improved (P < 0.001) BW gain and feed/gain ratio. There was no
      effect of lipase addition on chicken performance and nutrient utilization. When
      compared with canola oil, tallow-containing diets had a lower (P < 0.001)
      apparent fat digestibility and consequently a lower dietary AMEn content.
      Carbohydrase enzyme addition improved (P < 0.001) fat, starch, nitrogen, and
      nonstarch polysaccharide (NSP) digestibilities in the small intestine, improved
      AMEn, and reduced (P < 0.001) jejunal digesta viscosity in both fat types.
      Carbohydrase supplementation increased water-soluble (P < 0.001) and decreased
      water-insoluble (P < 0.001) NSP concentrations in the small intestine. The
      interaction between fat type and carbohydrase addition was only significant for
      fat digestibilities, with greater improvements seen for diets containing tallow.
      Significant interactions between carbohydrase addition and intestinal segment
      were noted for fat, starch, nitrogen, and NSP digestibilities, with the enzyme
      effects being greater in the jejunum than the ileum. It is evident from the
      present study that an appropriate carbohydrase preparation could eliminate the
      negative effects of soluble NSP on animal fat utilization in a wheat-based
      broiler diet.

PMID- 15510560
TI  - Detection of Campylobacter or Salmonella in turkey semen and the ability of
      poultry semen extenders to reduce their concentrations.
AB  - Campylobacter and Salmonella are the most commonly reported pathogens causing
      foodborne illness in the United States. In turkeys, the potential that semen used
      for artificial insemination is contaminated with these foodborne pathogens has
      not been investigated. Because semen on turkey farms is pooled and then used to
      inseminate multiple hens, contaminated semen could easily spread these bacteria
      throughout entire flocks via artificial insemination. The objectives of this
      study were to 1) determine if semen from commercial turkey farms contained these
      foodborne pathogens and 2) if present, evaluate the efficacy of semen extenders
      to reduce or eliminate Campylobacter and Salmonella from semen. Semen was
      collected from randomized pools of ejaculates from 10 to 30 toms per farm from 6
      flocks over a 7-wk period and, on occasion, was found to contain Campylobacter,
      Salmonella, or both. To evaluate the efficacy of semen extenders to reduce or
      eliminate pathogens, pooled ejaculates were challenged with Campylobacter or
      Salmonella and treated with commercial poultry extenders containing various
      concentrations of antibiotics or an antibiotic combination previously
      demonstrated to remove Campylobacter from mammalian semen. Results demonstrate
      that commercial turkey semen may contain Campylobacter or Salmonella, and the
      semen extenders tested either did not reduce the bacteria or reduced but did not
      eliminate these bacteria from semen. We concluded that semen may be a potential
      vehicle for Campylobacter transfer to hens, and, if this is true, development of
      a method for eliminating pathogens in semen before insemination could reduce the
      risk of colonization.

PMID- 15510561
TI  - Effects of aeration and storage temperature on Campylobacter concentrations in
      poultry semen.
AB  - Campylobacter is one of the most commonly reported bacterial causes of human
      foodborne infections in the United States. Recent evidence has demonstrated that
      Campylobacter is present in poultry semen and may contribute to the vertical
      transmission between the breeder hen and offspring. As Campylobacter is
      considered sensitive to oxygen and cold temperature, the objective of this study
      was to determine if aeration and storage temperature could reduce or eliminate
      Campylobacter in poultry semen. In 4 separate trials, pooled semen samples were
      collected from roosters or toms, diluted with a commercial poultry semen
      extender, and inoculated with an average of 10(7) cells/mL of a wild-type C.
      jejuni or C. coli semen isolate. Pooled ejaculates were then divided into 3
      aeration treatments: Control (no aeration), air, or oxygen (gently bubbled for 20
      min with atmospheric air or oxygen, respectively). Immediately after aeration,
      pooled semen samples were further divided to 3 test storage temperatures: 4, 23,
      or 42 degrees C. At 0, 2, 6, and 24 h of storage, samples were enumerated for
      Campylobacter. Aeration of the semen alone, or aeration with reduced temperatures
      (4 or 23 degrees C), did not reduce the amount of Campylobacter compared with the
      controls. Campylobacter concentrations were, however, reduced when stored at 42
      degrees C for 24 h. This effect is associated with reduced sperm viability and is
      therefore not a practical treatment of reducing Campylobacter in semen. It
      appears alternative methods will be needed to eliminate Campylobacter from
      poultry semen.

PMID- 15510562
TI  - Changing albumen-membrane adhesive forces during early embryonic development.
AB  - Using acoustic resonance analysis, it is possible to detect embryonic
      development. In fertile eggs, the resonant frequency suddenly decreases after
      about 100 h of incubation. Previous research has shown that this decrease
      coincides with changing mechanical properties of the albumen near the shell,
      caused by the formation of subembryonic fluid (SEF). In the present experiment,
      the adhesive forces between the shell, the membranes, and the albumen were
      measured before and after the decrease in the resonant frequency. The adhesive
      forces between shell and outer membrane and between the 2 membranes remained
      constant, whereas the adhesive force between the inner membrane and the albumen,
      indirectly measured by a Kjeldahl analysis, increased significantly. Whether the
      decrease in resonant frequency is caused by the increase of adhesive force
      between albumen and inner membrane or by the changed properties of the membranes
      (both of which are altered by dehydration of the albumen) is still open for
      discussion.

PMID- 15510563
TI  - Changes in prostaglandin F concentration in the uterus (shell gland) of the hen
      oviduct in relation to oviposition and estrogen.
AB  - The prostaglandin F (PGF) concentration of the uterus (shell gland) of the hen
      oviduct, measured by a radioimmunoassay, was found to increase slightly 6 h
      before oviposition and steeply immediately after oviposition. An intravenous
      injection of arginine vasotocin (AVT) caused the increase in the uterine PGF
      concentration and induced oviposition. When indomethacin was injected before the
      injection of AVT, the uterine PGF concentration was not increased, and the
      incidence of oviposition was reduced. Estrogen injection caused an increase in
      the uterine PGF concentration at 1 and 2 h after injection. Specific binding of
      the estrogen receptor of the uterine tissue increased 9 and 7 h before
      oviposition. The slight increase in the uterine PGF concentration 6 h before
      oviposition may be due to the action of estrogen via its receptor, and the steep
      increase immediately after oviposition may be caused by AVT released at the time
      of oviposition.

PMID- 15510564
TI  - Effect of ultimate pH on the physicochemical and biochemical characteristics of
      turkey breast muscle showing normal rate of postmortem pH fall.
AB  - This experiment aimed to study the effect of ultimate pH (pH(u)) on the
      biochemical and physicochemical characteristics of turkey breast muscle with
      normal rate of postmortem pH fall. Five hundred turkey toms (12 wk old, 10 kg
      live weight) were randomly chosen from a commercial flock. At 24 h postmortem, 64
      birds were randomly selected within the subgroup showing pH higher than 6.0 at 20
      min postmortem and pH(u) lower than 6.1. These pH levels were used to exclude
      pale, soft, and exudative (PSE) meat and dark, firm, and dry (DFD) meat,
      respectively. The pH(u) was significantly correlated with luminance (L*; r = 
      0.37) and yellowness (b*; r = -0.36) at 24 h postmortem, drip losses (r = -0.56
      to -0.62), thawing loss (r = -0.47), 80% compression (r = -0.29), yield of curing
      and cooking (r = 0.37), glycolytic potential at slaughter (r = -0.44) and lactate
      at 24 h postmortem (r = -0.47). Significant correlations were found between drip
      losses and compression test on cooked meat (r = 0.27 to 0.34). Cooking loss was
      correlated with WB shear force (r = 0.32). These results show that when PSE
      defects are excluded, the intensities of the correlations between pH(u) and meat
      quality traits are lower than those usually reported. The present data also
      indicate that the level of glycogen at time of slaughter poorly explains the
      variability in pH(u). Thus, further research is needed to identify the mechanisms
      explaining pH(u) variation in poultry muscle.

PMID- 15510565
TI  - Surviving severe sepsis: early recognition and treatment.

PMID- 15510566
TI  - Complementary and alternative medicine for hospice and palliative care.

PMID- 15510567
TI  - Empathy and compassion: where have they gone?

PMID- 15510568
TI  - The benefits and difficulties of academic collaboration.
AB  - People working in academia and in hospice organizations can help each other
      succeed while serving the needs of the people in hospice care. This is especially
      important in times of tight budgets for all concerned. Hospice organizations
      would benefit from educating themselves about research and participating as
      partners in research activities. Collaborating researchers must be willing to
      discuss their research with members of hospice organizations and explain how it
      is to be structured, conducted, and how it can improve services. Researchers can
      make scientific investigation and its findings more user-friendly and
      understandable. The hospice organization can set up forums that promote dialogue
      between hospice professionals and researchers at meetings, conferences, and
      symposia that will benefit the academic group, hospice organization, and,
      ultimately, people in hospice care.

PMID- 15510569
TI  - Family caregiver satisfaction with care at end of life: report from the cultural
      variations study (CVAS).
AB  - The objective of this study was to examine differences in family caregiver
      satisfaction with care at end of life based on site of death, in an observational
      study involving advanced cancer patients and their family caregivers. The study
      was based on follow-up interviews with 28 family caregivers of 28 patients who
      died during a two-year prospective study involving 68 patients and 68 family
      caregivers. Telephone interviews addressed the circumstances of the patients
      'death, their satisfaction with the care provided to the patient, and their
      satisfaction with how well they were attended to by health providers. There were
      no associations between site of death (died at home vs. did not die at home) and
      family caregiver satisfaction with the overall care provided to the patient.
      However family caregivers of patients who died at home responded that they
      thought the patient was more at peace (with respect to spiritual and religious
      matters) than did family caregivers of patients who did not die at home (p =
      0.003). Family caregivers of patients who died at home appeared to feel less
      satisfied with the attention paid to their own wishes regarding the patient's
      care (p = 0. 13), less satisfied with the emotional support provided to them by
      healthcare personnel taking care of the patient (p = 0. 08), and less satisfied
      with communication from health providers (p = 0. 11). Findings indicate that
      although dying at home appears to provide a more peaceful death for the patient,
      it may also distance family caregivers from health professionals and leave them
      feeling less supported during the patient's last days of life.

PMID- 15510570
TI  - Hospice staff attitudes towards telehospice.
AB  - Telemedicine, defined as the use of advanced telecommunication technologies to
      bridge geographic distance and improve delivery of care, is perceived by many as
      a way to eliminate barriers to quality care at the end of life. The use of
      telemedicine in hospice, known as telehospice, is a novel approach to such care,
      and few pilot studies have investigated its feasibility. The purpose of this
      study was to assess hospice providers 'perceptions of telehospice. A focus group
      session was conducted with 10 staff members from five hospice agencies in
      Missouri. Participants included administrators, nurses, and social workers.
      Overall, providers had a positive perception of telehospice and found that the
      use of videophone technology enhanced care by enabling providers, patients, and
      family members a means to communicate. However, they emphasized that it was an
      additional tool and not a substitute for actual visits. Issues of privacy and
      usability were also raised.

PMID- 15510571
TI  - The cost of breathing: an economic analysis of the patient cost of home oxygen
      therapy.
AB  - The oxygen concentrator is a popular means of delivering supplemental oxygen to
      the home hospice patient. The technology is notable for its reliability,
      convenience, and ease of use. It is the most cost effective of the various oxygen
      delivery systems from the institutional standpoint. Cost effectiveness from the
      patient standpoint has not previously been reported. We present a brief analysis
      of the cost of operating such a device from the perspective of the patient and
      suggest possible ways of addressing this cost.

PMID- 15510572
TI  - Pastoral care, spirituality, and religion in palliative care journals.
AB  - With the growth and development of palliative care, interest in pastoral care,
      spirituality, and religion also seems to be growing. The aim of this article is
      to review the topic of pastoral care, spirituality, and religion appearing in the
      journals of palliative care, between January 1984 and January 2002.

PMID- 15510573
TI  - Programmatic barriers to providing culturally competent end-of-life care.
AB  - Despite many efforts to increase access to end-of-life care, culturally diverse
      groups are still not being served. Interviews of 22 hospice and palliative care
      program directors in one southeastern state indicated that directors
      overestimated how well programs are doing in meeting the needs of diverse groups
      but were very interested in implementing cultural diversity training for their
      staff Those who were more concerned about such issues had recruited more diverse
      volunteers into their programs. The presence of diverse staff or volunteers
      predicted a more diverse patient population. A number of efforts were underway to
      develop cultural competence and provide culturally competent care. Several
      directors reported no efforts in this direction, however Directors described
      programmatic barriers and resources needed. The authors concluded that directors
      should provide leadership in their agencies in welcoming diversity. Implications
      for further research and work within the larger end-of-life care field are
      discussed.

PMID- 15510574
TI  - Communication in palliative medicine: a pilot study of a problem list to capture
      complex medical information.
AB  - We developed a one-page, structured problem list to facilitate communication of
      complex patient information in palliative medicine. The problem list was
      developed to provide a concise record of the complex problems presented by
      patients with advanced disease. It was also seen as a mechanism to facilitate
      interdisciplinary and multidisciplinary communication and continuity of care in
      the hospital and in the community. One hundred consecutive patients, who were
      newly referred to our palliative medicine program, were prospectively surveyed to
      gain clinical experience with the problem list. Ninety patients had cancer
      diagnoses. The median age was 69 (range 20-90 years), the male to female ratio
      was 2:1, and the median Eastern Cooperative Oncology Group (ECOG) performance
      status was 3 (range 0-4). The population was 78 percent Caucasian. The median
      number of symptoms per patient was 5 (range 0-13), which was similar for cancer
      and noncancer patients. Overall, gastrointestinal symptoms and pain were the most
      common symptoms. Pain was more common in cancer patients, and respiratory
      problems were the most common among noncancer patients. Noncancer patients had
      better performance status. Based on this experience, we believe a problem list
      facilitates succinct communication of complex patient information essential to
      optimal patient care. Proposed modifications are discussed.

PMID- 15510575
TI  - Establishing the safety and efficacy of an opioid titration protocol.
AB  - The primary goal of this single-group study was to determine the safety of a
      standard opioid titration order sheet to manage pain in ambulatory cancer
      patients. Secondary goals were to examine opioid toxicity and efficacy of this
      pain protocol. Twenty-seven patients who required fixed-dose opioids and who had
      uncontrolled pain were enrolled. All patients had their initial opioid dose
      titrated by the study physician using the opioid titration order sheet. Data were
      obtained by the study nurse during a weekly telephone interview and used to
      determine if pain was controlled. After initial titration, a trained study nurse
      titrated opioid doses based upon the standing order sheet. At each contact,
      patients were assessed for adverse effects, pain intensity, and analgesics used.
      Patients who completed the four-week trial (n = 17) did not differ from patients
      who did not complete the trial. No adverse effects were observed in 39 opioid
      titrations completed by the study nurse. Opioid toxicities, worst pain, usual
      pain, and pain-related distress declined from baseline to week four Patients who
      were adherent to their prescribed medications reported significantly lower pain
      intensity and distress (ps < or = . 06). The opioid titration order sheet, used
      by a trained nurse, is safe to use in ambulatory cancer patients who have
      moderate to severe pain. Common opioid toxicities were reduced. The protocol also
      demonstrated initial efficacy in improving worst and usual pain and pain-related
      distress. Further research to establish efficacy of the protocol is recommended.

PMID- 15510577
TI  - The perfect hospice patient.

PMID- 15510576
TI  - Medical house officers' attitudes toward vigorous analgesia, terminal sedation,
      and physician-assisted suicide.
AB  - In 2000, the authors surveyed 236 medical house officers in three internal
      medicine residency programs in Connecticut to assess attitudes toward vigorous
      analgesia, terminal sedation, and physician-assisted suicide. The goal was to
      identify associations between these attitudes and training, demographic, and
      religious factors. The results of the study indicated that most medical house
      officers supported vigorous analgesia, the majority supported terminal sedation,
      but only a minority supported physician-assisted suicide. Some house officers'
      attitudes toward terminal sedation and assisted suicide may have been influenced
      by their religious commitments and the pressures of training.

PMID- 15510578
TI  - Case study: denying admission of a suicidal patient to a nursing home.

PMID- 15510579
TI  - Mold-induced hypersensitivity pneumonitis.
AB  - Mold-induced hypersensitivity pneumonitis results from macrophage- and lymphocyte
      driven inflammation, which may be attributable to contaminated humidifiers or
      heating-ventilation systems or sources in homes, schools, or workplaces. A case
      may be suspected when there is water intrusion or inadequate drainage. Some
      fungal causes include species of Alternaria, Aspergillus, Cryptostroma,
      Penicillium, Pullularia, Rhodotorula, and Trichosporon. The differential
      diagnosis includes mold-induced asthma, sick building syndrome, mass psychogenic
      illness (epidemic hysteria), unjustified fears of "toxic" molds, and conditions
      causing recurrent pneumonitis.

PMID- 15510580
TI  - Pentobarbital desensitization in a 3-month-old child.
AB  - Barbiturates, a class of medications commonly used as antiepileptics and
      sedatives, are known to cause adverse reaction, with the most commonly reported
      immune-mediated reactions being anticonvulsant hypersensitivity syndrome. Other
      types of allergic reactions such as immediate hypersensitivity reactions also can
      occur. We present a 3-month-old child with refractory generalized convulsive
      status epilepticus who required pentobarbital therapy in the context of
      phenobarbital sensitivity because of progressive generalized seizures
      unresponsive to other aggressive therapies. Skin tests to pentobarbital and
      phenobarbital were negative. In the intensive care unit setting, intravenous
      pentobarbital desensitization was performed without reaction. To our knowledge,
      this is the first reported protocol for pentobarbital desensitization.

PMID- 15510581
TI  - Mucoid impaction: a localized form of allergic bronchopulmonary aspergillosis.
AB  - Mucoid impaction is defined as the obstruction of proximal bronchi by mucous
      plugs and exudates. There are striking similarities between patients with mucoid
      impaction and those with allergic bronchopulmonary aspergillosis (ABPA), often
      referred to as "mucoid microimpaction." We evaluated three patients with mucoid
      impaction for diagnostic criteria of ABPA and human leukocyte antigen type. We
      found that certain human leukocyte antigen types were common among mucoid
      impaction patients and those with ABPA. It is possible that patients with mucoid
      impaction could represent a localized form of ABPA.

PMID- 15510582
TI  - Salmon caviar-induced anaphylactic shock.
AB  - Foods, particularly shellfish and nuts, are commonly implicated as causes of
      anaphylaxis. Salmon caviar, to our knowledge, is an exceedingly rare cause of
      anaphylactic shock. This study describes a patient who experienced anaphylactic
      shock on her initial ingestion of caviar. Skin testing and inhibition assays
      using the enzyme-linked immunosorbent assay were performed. On the percutaneous
      test, the patient had a 7 x 9 mm/15 x 55 mm wheal/ erythema reaction to caviar
      liquid. Caviar liquid caused 68, 73, and 73% inhibition of immunoglobulin E (IgE)
      binding at concentrations of 0.01, 0.1, and 1.0 mg/mL in an enzyme-linked
      immunosorbent assay, respectively. There was no evidence for IgE antibodies that
      could be demonstrated to bind to the caviar eggs. Despite using both metoprolol
      and lisinopril, the patient responded promptly to subcutaneous epinephrine. This
      report indicates that an IgE-mediated response occurred after caviar ingestion.
      Although she experienced anaphylactic shock, the patient recovered quickly after
      epinephrine administration despite routine use of a 3-adrenergic blocker and
      angiotensin-converting enzyme inhibitor.

PMID- 15510583
TI  - Clinical characteristics and pattern of skin test reactivities in shellfish
      allergy patients in Hong Kong.
AB  - Allergens from crustaceans and mollusks exhibit extensive cross-reactivity in
      vitro. However, the degree and pattern of cross-reactivity between different
      shellfish species in vivo is still unclear. The objective of this study was to
      determine the clinical characteristics of shellfish allergic patients in Hong
      Kong and the pattern of skin test reactivities to the different species. This
      cohort study involves patients attending the allergy clinic of a large teaching
      hospital for suspected shellfish allergy. Each subject underwent skin-prick tests
      to eight species of shellfish and house-dust mites. Eighty-four consecutive
      patients were tested. Twenty-eight patients reported a history of severe
      anaphylaxis. Fourteen patients had no positive shellfish skin test and were
      excluded. There were 183 positive shellfish skin tests, with an average of 2.61
      positive tests per subject. Ninety percent of subjects also had positive skin
      tests to house-dust mites. Overall, 65. 7% of subjects had more than one positive
      skin test to shellfish. There were strong statistical associations between
      species belonging to the same order but also between some mollusks and
      crustaceans. We found a high degree of skin test cross-reactivity between
      different species of shellfish and between shellfish and house-dust mites.
      Therefore, patients with a history of shellfish allergy should be cautious with
      all types of shellfish.

PMID- 15510584
TI  - High frequency of DD polymorphism of the angiotensin-converting enzyme gene in
      Turkish asthmatic patients.
AB  - The aim of this study is to detect the incidence of the angiotensin-converting
      enzyme (ACE) gene polymorphism in Turkish asthmatic patients and to examine
      whether there is an association between the disease and ACE gene polymorphism. In
      our study, the genomic DNA of 100 asthmatic patients and 88 healthy subjects was
      analyzed Genomic DNA was isolated from peripheral blood by using standard
      methods. The intron 16 of the ACE gene was amplified by the polymerase chain
      reaction (PCR) method using primers ACE and ACEX to examine the presence and
      absence of a 287-base pair (bp) DNA fragment that showed I/D polymorphism
      genotypes. PCR products were separated by agarose gel electrophoresis and were
      visualized by a charge-coupled device camera. Serum ACE activities were measured
      using an ACE kit. The results were evaluated statistically using the chi-square
      test and one-way analysis of variance. Although the population of patients with
      asthma was characterized by a higher frequency (30%) of the DD genotype of ACE,
      they were characterized by lower frequency (48%) of the ID genotype of ACE (DD,
      16%, and ID, 64%, in healthy control subjects). The frequency of the I and D
      alleles of the ACE gene was not significantly different between asthmatic
      patients (0.46/0.54) and healthy controls (0.52/ 0.48). In addition, in both
      asthmatic patients and controls, there was a significant decrease of the levels
      of ACE activity in individuals that have II genotypes when compared with
      individuals that have DD genotypes. ACE activities were increased significantly
      in all asthmatic patients (67.20 +/- 1.95 IU/L) compared with all healthy
      controls (60.90 +/- 2.12 IU/L).

PMID- 15510585
TI  - Readministration of high-dose methotrexate in a patient with suspected immediate
      hypersensitivity and T-cell acute lymphoblastic lymphoma.
AB  - There is a paucity of literature addressing the management of methotrexate (MTX)
      hypersensitivity. We developed a high-dose MTX readministration protocol based on
      a modified, prolonged carboplatin desensitization protocol. Over 1.5 hours,
      1/1000 of the total intravenous dose was administered followed by 1/100 over 1.5
      hours, 1/10 over 6 hours, and the rest of the full dose over 24 hours. MTX
      readministration was successfully tolerated on three occasions in a 17-year-old
      male patient with T-cell acute lymphoblastic lymphoma and a history of urticarial
      reactions to MTX. This high-dose MTX readministration protocol may be valuable
      for treating patients with T-cell acute lymphoblastic lymphoma and suspected
      immediate MTX hypersensitivity.

PMID- 15510587
TI  - Localized seminal plasma protein hypersensitivity.
AB  - Human seminal plasma protein hypersensitivity is a rare disorder. Since the first
      case report in 1958, allergic reactions to semen have gone relatively unnoticed
      or improperly diagnosed. Dozens of medical case reports and research prove that
      allergy to seminal fluid is a legitimate health concern.

PMID- 15510586
TI  - Small bowel of patients with asthma and allergic rhinitis: absence of
      inflammation despite the presence of major cellular components of allergic
      inflammation.
AB  - Eosinophils participate in the pathogenesis of inflammatory diseases of the
      respiratory tract and the gut. We investigated the constitutive presence of
      eosinophils and mononuclear cells in the macroscopically normal duodenal mucosa
      of patients with asthma and allergic rhinitis. Macroscopically normal duodenal
      specimens were obtained at routine endoscopy for upper gastrointestinal symptoms
      from 16 patients with asthma and 13 patients with allergic rhinitis. Twelve
      nonatopic patients with irritable bowel syndrome were studied as controls.
      Specimens were analyzed by immunohistochemistry using a panel of antibodies to
      human eosinophil cationic protein clone EG1 (EG1) and clone EG2 (EG2), anti-human
      interleukin (anti-hIL)-5, anti-hIL-4, anti-CD4, and anti-CD68. Significantly
      increased numbers of eosinophils stained with EG1 and EG2 were found in the
      duodenum of patients with asthma and allergic rhinitis compared with controls. IL
      5+ cells and IL-4+ cells were detected in significantly increased numbers in the
      duodenal mucosa of patients with asthma and rhinitis compared with controls.
      Mononuclear cells expressing CD4 (helper T cells) and CD68 (macrophages) also
      were significantly increased in the duodenal mucosa of asthma and rhinitis
      compared with controls. Accumulation of eosinophils in conjunction with IL-4+
      cells and IL-5+ cells in the noninflamed duodenal mucosa may reflect a
      predominant T helper cell subset 2 systemic immune response in patients with
      asthma and allergic rhinitis. The absence of intestinal inflammation despite the
      marked presence of cells implicated in the allergic inflammation suggests that
      local mechanisms might determine the state of nonresponsiveness in the gut mucosa
      of patients with asthma and allergic rhinitis.

PMID- 15510588
TI  - Allergic bronchopulmonary aspergillosis masquerading as invasive pulmonary
      aspergillosis.
AB  - Allergic bronchopulmonary aspergillosis (ABPA) is a noninvasive complex
      hypersensitivity reaction that occurs in immunocompetent patients with asthma.
      Aspergillus can invade and disseminate, but this more commonly occurs in severely
      immunocompromised patients receiving high-dose corticosteroids. We report the
      case of a 13-year-old immunocompetent male patient with moderate persistent
      asthma who appeared to have invasive pulmonary aspergillosis on radiographic
      studies. With further evaluation and workup, it was determined that the patient
      did not have invasive pulmonary aspergillosis, but that he met the diagnostic
      criteria for ABPA. Although initially there was a deceptive invasive appearance,
      proper identification of ABPA facilitated selection of corticosteroid treatment
      that resulted in prompt clearing of the concerning infiltrates.

PMID- 15510590
TI  - Assessing breast cancer risk: genetic factors are not the whole story.
AB  - Genetic syndromes that convey a significant risk of breast cancer are responsible
      for a small but significant percentage of these cancers. However, the vast
      majority of breast cancers occur in women with no family history of the disease.
      Nongenetic risk factors include age, previous breast disease, breast tissue
      density, radiation exposure, and lifestyle factors, such as weight, exercise, and
      alcohol consumption. In this article, the authors outline genetic and other risk
      factors for breast cancer, explore risk-reduction strategies, and encourage
      primary care physicians to assess breast cancer risk in all their patients.

PMID- 15510591
TI  - Managing early breast cancer: prognostic features guide choice of therapy.
AB  - In the United States, more than 90% of breast cancer diagnoses occur in an early
      stage of the disease. That so much detection happens early bodes well for the
      patient. However, it is only one part of the clinical picture. Various features,
      such as lymph node involvement and receptor status, help predict outcome, aid in
      treatment selection, and are crucial factors in survival. Here, the authors
      present the current considerations and treatment guidelines for early-stage
      breast cancer.

PMID- 15510592
TI  - Care of the breast cancer survivor: increased survival rates present a new set of
      challenges.
AB  - Earlier detection of invasive and noninvasive breast cancer and more effective
      treatments have led to both an improved prognosis for women with breast cancer
      and an increasing number of long-term survivors. However, such advances present
      various physical and emotional health challenges to patients facing breast cancer
      and its aftermath. Thus, understanding of the specific medical and psychosocial
      problems associated with survivorship is paramount in primary care.

PMID- 15510593
TI  - The promise of atypical antipsychotics: fewer side effects mean enhanced
      compliance and improved functioning.
AB  - Five new antipsychotic drugs introduced in the United States in the last decade
      offer physicians the ability to treat patients with schizophrenia and bipolar
      mania without the adverse effects of the first-generation antipsychotics. In this
      article, the authors discuss the advantages and side effects of these agents and
      present a guide to help physicians choose the optimal drug in the most favorable
      formulation for each patient.

PMID- 15510594
TI  - Patient Notes: motion sickness.

PMID- 15510595
TI  - A cytokeratin- and calretinin-negative staining sarcomatoid malignant
      mesothelioma.
AB  - Malignant Mesothelioma, or mesothelioma, is a mesothelial-based malignancy that
      may occur in the pleura, pericardium and peritoneum. Mesothelioma is a very
      aggressive cancer with limited treatment, and a median survival of about 1 year.
      At times, the diagnosis of mesothelioma may be problematic. The final diagnosis
      of mesothelioma relies on histology and often is dependent upon
      immunohistochemistry. It is generally assumed that mesotheliomas must stain
      positive for cytokeratin and calretinin and negative staining for these markers
      would rule out the diagnosis. We encountered a patient with a pleural-based,
      cytokeratin- and calretinin-negative sarcomatoid malignancy. These negative
      stainings would rule out the diagnosis of mesothelioma but, after careful
      consideration of the patient's clinical records, and additional histological and
      immunohistochemical studies, we conclude that this patient suffered from
      mesothelioma of the sarcomatoid type.

PMID- 15510596
TI  - Overexpression of the Wilms' tumor gene WT1 in esophageal cancer.
AB  - BACKGROUND: The Wilms' tumor gene WT1 is overexpressed in various kinds of solid
      cancers. However, it remains unclear whether WT1 is expressed in esophageal
      squamous cell carcinoma. MATERIALS AND METHODS: Expression of the WT1 gene was
      examined by real-time RT-PCR in 12 esophageal squamous cell carcinoma (ESCC) and
      by immunohistochemistry in 9 of these 12 and another 29. RESULTS: Real-time RT
      PCR showed that the WT1 mRNA was overexpressed in all of the 12 ESCC examined
      Immunohistochemical analysis showed that the WT1 protein was overexpressed in
      ESCC cells in 36 (95%) of the 38 examined Furthermore, expression of the WT1
      protein was examined in 20 esophageal squamous dysplasia. The WT1 protein was
      overexpressed in 5 (45%) out of 11 mild dysplasia and in 8 (89%) out of 9
      moderate to severe dysplasia. CONCLUSION: These results may indicate an important
      role of the WT1 gene in the tumorigenesis of ESCC.

PMID- 15510597
TI  - The gamma2 chain of laminin-5 as an indicator of increased risk for recurrence in
      T1 stage tongue cancer.
AB  - BACKGROUND: Treatment of small, localized tongue cancer is an act of balance
      between sufficiently extensive surgery and/or radiotherapy for safe cure, and
      minimizing treatment-related morbidity. The biological aggressiveness of these
      cancers is variable and conventional histopathology does not give sufficient
      information concerning the risk for local or regional recurrence. Laminin-5 is an
      extracellular matrix protein noted to have special importance for epithelial cell
      invasion. PATIENTS AND METHODS: We investigated 43 diagnostic biopsies from
      patients with T1 tongue cancer treated with wedge excision only.
      Immunohistochemical analysis was performed using a polyclonal antibody against
      the gamma2 chain of laminin-5. RESULTS: Thirty-six specimens were evaluated and
      16 patients had a recurrence. A staining pattern of 50% or more was seen in the
      majority of patients (75%) with tumor recurrence and in fewer patients (45%)
      without recurrence. CONCLUSION: In order to optimize treatment for the individual
      T1 tongue cancer patient, immunostaining against laminin-5 appears to be one
      possible useful tool.

PMID- 15510598
TI  - Hypertension and risk of brain metastasis from small cell lung cancer: a
      retrospective follow-up study.
AB  - BACKGROUND: Although metastatic brain cancer is one of the most common forms of
      cancer, little is known about the factors associated with its development. We
      examined the hypothesis that hypertension may increase the risk for brain
      metastasis (BM) in patients with primary small cell lung cancer (SCLC). MATERIALS
      AND METHODS: A retrospective review of medical charts of patients diagnosed with
      SCLC between June, 1986 and June, 2003 at MeritCare in Fargo, ND, USA, was done
      to determine which of these patients subsequently developed brain metastases. The
      effects of hypertension, age, gender, body mass index and the site of SCLC on the
      risk of developing BM were examined using both univariate and multivariable Cox
      proportional-hazards regression models. Two-way interactions between hypertension
      and other covariates were also included in the analyses. RESULTS: Two hundred and
      thirty-two patients were identified with SCLC and 185 patients were eligible for
      this study. Eighty-five (45.9%) patients developed BM. Over 54% of SCLC occurred
      in the right lobe and more than 70% of the patients with BM had them in multiple
      locations. The risk of BM is significantly higher in younger patients (p-value <
      0.03). Univariate analysis showed a hazard ratio (HR) for hypertension of 1.01
      (95% Confidence Interval (CI) 0.6-1.6) for BM from SCLC. The multivariable Cox
      model showed an adjusted HR for hypertension of 1.06 (95%CI 0.7-1.6) for BM from
      SCLC CONCLUSION: As has been consistently observed for other lung cancers, SCLC
      is more common in the right lung. The higher incidence of BM in younger patients
      suggests that more aggressive therapy is needed in these patients. Hypertension
      does not appear to increase the risk of BM from SCLC.

PMID- 15510599
TI  - Ursodeoxycholic acid treatment in IBD-patients with colorectal dysplasia and/or
      DNA-aneuploidy: a prospective, double-blind, randomized controlled pilot study.
AB  - BACKGROUND & AIMS: There is an increased risk of colorectal carcinoma (CRC) in
      patients with longstanding, extensive colonic inflammatory bowel disease (IBD).
      Primary sclerosing cholangitis, family history of CRC, mucosal dysplasia and DNA
      aneuploidy are other risk factors. Recently, results from animal studies have
      shown that the bile acid ursodeoxycholic acid (UDCA) has a favourable impact on
      experimentally-induced CRC/neoplasia in rats. The aim of this proof of the
      concept study was to explore the possible preventive/reverting effects of UDCA in
      patients with colorectal IBD with existing findings of low grade dysplasia and/or
      DNA-aneuploidy. PATIENTS AND METHODS: Nineteen patients (13 UC, 6 CD, median age
      43 years) with long-standing, extensive IBD (median duration 21 years), with
      previous findings of low-grade dysplasia and/or DNA-aneuploidy, were randomized
      to receive either UDCA (500 mg b.i.d) (n=10) or placebo (n=9) in a controlled,
      double-blind, two-year study. Colonoscopy with multiple biopsies for
      histopathology and for DNA-flow cytometry was performed at the start and at six
      month intervals during the study period. The primary outcome was the need for
      colectomy due to progression of dysplasia. Changes in dysplasia and DNA
      aneuploidy scores were also assessed. RESULTS: There were no significant
      differences in the overall composed score between the two groups, either at study
      start or during the study period. In the placebo group one patient had a
      progression of dysplasia into high-grade and one patient developed DALM with low
      grade dysplasia; both had a colectomy. In contrast, no UDCA-treated patient had
      progression of dysplasia. CONCLUSION: UDCA may prevent further progression of
      manifest low-grade dysplasia in colorectal IBD. Prolonged treatment or an
      increased dose may be needed to fully exploit the chemopreventive properties of
      this compound.

PMID- 15510600
TI  - Radiofrequency Heat Ablation and Vertebroplasty in the treatment of neoplastic
      vertebral body fractures.
AB  - BACKGROUND: Metastatic cancer is the most common malignant disease of the
      skeletal system. Traditionally, conventional fractionated external beam
      radiotherapy has been the treatment of choice. Recently, minimally invasive
      surgical techniques (MISS) have been added to the therapeutic armamentarium. The
      purpose of our study was to assess the effectiveness and safety of Radiofrequency
      Heat Ablation and Vertebroplasty in the treatment of neoplastic Vertebral
      Compressive Fractures (VCF). The aim of radiofrequency heat ablation is to
      destroy the tumor tissue before stabilizing the vertebra through the intrasomatic
      injection of cement. PATIENTS AND METHODS: We treated patients with unremitting
      pain over spine, in absence of symptomatic spinal cord or roots compression and
      refractory to conventional therapeutic options such as radiation therapy,
      chemotherapy, surgery and use of analgesics. RESULTS: The method demonstrated
      swift pain relief associated with an evident augmentation in the weight-bearing
      resistance. CONCLUSION: The association of Radiofrequency Heat Ablation and
      Vertebroplasty is an effective, simple and safe treatment of vertebral collapse
      consequent to metastases.

PMID- 15510601
TI  - Changes in serum IgG oligosaccharide chains with prostate cancer progression.
AB  - BACKGROUND: Changes of serum IgG oligosaccharide chain structure have been found
      in B cell lineage tumors and autoimmune diseases. Currently, the cancer
      associated carbohydrate epitopes CA72-4 and CA15-3 are used as serum tumor
      markers. In the present study, we analyzed the structure of serum IgG
      oligosaccharide chains in prostate cancer (PCa) patients using the simple new
      method of fluorophore-associated carbohydrate electrophoresis (FACE). We also
      evaluated the relationship between changes of serum IgG oligosaccharide chain
      structure and serum concentration of prostate-specific antigen (PSA). MATERIALS
      AND METHODS: The structure of serum IgG oligosaccharide chains from 12 PCa
      patients (6 localized cancer, 6 metastatic cancer) and 10 healthy controls was
      evaluated by FACE. PSA levels in serum were determined by enzyme immunoassay.
      RESULTS: Fr 1 (monogalactosyl oligosaccharide) and Fr 2 (digalactosyl
      oligosaccharide) decreased significantly (p<0.05), while Fr 4 (agalactosyl IgG
      oligosaccharide) increased with PCa tumorprogression. The Fr 4/Fr 1+2 ratio in
      metastatic PCa patients was significantly higher than in healthy controls
      (p<0.05), and there was a significant correlation (r=0.84, p<0.05) between serum
      PSA levels and the Fr 4/Fr 1+2 ratio in all patients with PCa. CONCLUSION: The
      changes of serum IgG oligosaccharide chain structure with PCa progression are
      based on the abnormality of glycosylation in PCa metastasis. Therefore, the
      analysis of serum IgG oligosaccharide chain structure by FACE may be an auxiliary
      indicator of PSA for monitoring PCa progression.

PMID- 15510602
TI  - Radiotherapy for localized hormone-refractory prostate cancer in Japan.
AB  - BACKGROUND: The role of radiotherapy for patients with localized hormone
      refractory cancer has not been well documented. MATERIALS AND METHODS: The
      Patterns of Care Study in Japan examined the records of 311 patients with
      prostate cancer treated with radiotherapy during the period 1996--1998. Of them,
      61 patients (19.6%) with regionally localized hormone-refractory cancer were
      selected. Local progression or biochemical failure was observed after a median
      duration of 15.9 months of androgen deprivation. At the time of radiotherapy, 49
      patients (80.4%) had T3-4 tumors and 15 (26.8%) had regional lymph node
      metastases. External beam radiotherapy was performed with a median total dose of
      60 Gy. RESULTS: Although distant metastases or regional lymph node metastases
      were seen in 22 patients (36.1), local progression was observed in one patient
      (1.6%). The five-year overall and progression-free survival rates were 51.6% and
      43.5%, respectively. CONCLUSION: Radiotherapy had an excellent local control rate
      for hormone-refractory cancer.

PMID- 15510603
TI  - PET scanning evaluation of response to imatinib mesylate therapy in
      gastrointestinal stromal tumor (GIST) patients.
AB  - BACKGROUND: Unresectable or metastatic gastrointestinal stromal tumors (GISTs)
      exhibit a dynamic clinical course, with no evidence of benefit from any standard
      cytotoxic chemotherapy and an inevitably fatal outcome. With the introduction of
      Imatinib, an oral drug able to inhibit the KIT receptor tyrosine kinase, new
      questions arise regarding our ability to monitor treatment response with
      conventional methods and optimally manage such patients on treatment with new
      agents. MATERIALS AND METHODS: Herein we report two cases of patients with a
      history of GIST in treatment with Imatinib. RESULTS: After 4 weeks from treatment
      start, CT scan evaluation demonstrated a massive increase in the size of
      metastatic lesions, but a confirmatory PET excluded, in both patients, the
      presence of any metabolic activity in the previously known metastatic sites.
      Imatinib therapy was continued with subjective clinical benefit for 12 further
      months before a PET scan-confirmed disease progression had occurred in one
      patient and is still ongoing after 15 months in the other. CONCLUSION: These
      cases open the obvious question of whether conventional imaging techniques are
      adequate to assess the response to Imatinib treatment in GIST patients.

PMID- 15510604
TI  - Malignant intestinal obstruction: useful technical advice in self-expanding
      metallic stent placement.
AB  - BACKGROUND: The use of endoluminal self-expanding metallic stents is an effective
      alternative to surgery in neoplastic gastrointestinal tract obstructions. It is
      often difficult to mark the proximal segment of the stricture under fluoroscopic
      guidance (due to patient movements or change of markers' position). PATIENTS AND
      METHODS: We placed Ultraflex precision colonic stent (Microvasive, Boston
      Scientific) in ten patients with neoplastic stricture of the rectosigmoid colon.
      Before placement of the delivery catheter, a radiopaque proximal marker was
      identified on the delivery catheter under fluoroscopic guidance. The external
      side of the delivery catheter was coloured (in correspondence with the radiopaque
      marker) with non toxic colour. After the introduction of the delivery catheter,
      we placed the proximal coloured marker just above the distal tumour margin under
      endoscopic guidance. RESULTS: The procedure was successful in relieving the
      obstruction in all patients, without mortality or complications. In all patients
      the coloured marker was identified and the stent correctly placed. CONCLUSION:
      The location of a coloured marker in the external side of the delivery catheter
      permits an accurate and correct placement of the stent, without unnecessary
      exposure to X-rays.

PMID- 15510605
TI  - Pleomorphic lipoma: a definite histopathological entity.
AB  - Pleomorphic lipomas are rare benign tumours that can resemble a variety of
      malignant tissue tumour on histological examination. We describe a case of
      pleomorphic lipoma arising on the posterior aspect of the neck of a 70-year-old
      man, successfully treated by surgical excision. A review of the literature is
      presented, summarizing the principal clinical and morphological characteristics
      of this rare tumor.

PMID- 15510606
TI  - Microsatellite status and cell cycle associated markers in rectal cancer patients
      undergoing a combined regimen of 5-FU and CPT-11 chemotherapy and radiotherapy.
AB  - BACKGROUND: Microsatellite instability (MSI) and expression of cell cycle-related
      markers may predict a favorable outcome in colorectal cancer patients. The aim of
      this study was to elucidate the molecular profiles of patients with rectal
      cancers treated with neoadjuvant chemotherapy (5-Fluorouracil and CPT-11),
      radiotherapy and surgery that correlate with response to therapy. PATIENTS AND
      METHODS: Fifty-seven patients with rectal cancer were treated with the same
      preoperative chemotherapy regimen, radiotherapy (45 to 54 Gy) followed by
      surgery. The microsatellite status, the expression of the mismatch repair
      proteins MLH1 and MSH2 and p21WAF1/C1PI, p27, bcl-2, topoisomerase II (topo II)
      and Ki-67 were assessed in the pretreatment biopsies. The response to adjuvant
      therapy was categorized in the resected specimens as complete response (CR, no
      microscopic residual tumor present) and partial response (PR, tumor present).
      RESULTS: p21WAF1/C1PI, expression characterized the CR with 12 out of 30 tumors
      (40%) positive for this marker. None of the patients whose tumors did not express
      p21WAFI/C1PI (10 patients) was a CR (p=0.011). Overall, the tumors with CR also
      showed higher expression of bcl-2, Ki-67, topo II and p27. However, p53 was more
      frequently expressed in the PR tumors. Tumors with high microsatellite
      instability showed CR (3/5, 60%) more often than PR, whereas tumors with stable
      microsatellites showed PR (26/36, 80%) more often than CR (p=0.099). CONCLUSION:
      We conclude that a molecular profile characterized by high microsatellite
      instability with loss of mismatch repair protein expression and p21WAF1/C1PI is
      predictive of an improved response to neoadjuvant treatment with 5-FU, CPT-11 and
      radiation therapy.

PMID- 15510607
TI  - Surgical outcome of serosa-negative advanced gastric carcinoma.
AB  - The purpose of the present study was to clarify prognostic factors and to
      investigate appropriate therapeutic strategies for T2 gastric carcinoma. A total
      of 297 consecutive patients with T2 gastric carcinoma (T2a; 130, T2b; 167) were
      enrolled in this study. The overall 5-year survival rate was 75.3%. There was a
      significant difference in survival between T2a and T2b tumor. Multivariate
      analysis showed that age, depth of invasion and lymph node metastasis
      independently influenced prognosis. Peritoneal recurrence was frequently observed
      in 37 patients. Multivariate analysis revealed that lymph node metastasis was an
      independent predictive factor for peritoneal recurrence. Furthermore, the
      quantity of the stroma was an independent prognostic factor for hematogenous
      metastasis, and lymph node metastasis for lmphatic metastasis. Prophylactic
      therapeutic strategy should be advised for patients with many metastatic lymph
      nodes, for peritoneal or lymphatic recurrence and in patients with "medullary"
      stroma for hematogenous recurrence.

PMID- 15510608
TI  - Aspirin use and mortality from cancer in a prospective cohort study.
AB  - There is evidence that use of aspirin offers several potential health benefits
      including cancer prevention and cardiovascular disease prevention. The purpose of
      this study was to assess the association between aspirin use and death from
      cancer and cardiovascular diseases with a special emphasis on cancer mortality.
      MATERIALS AND METHODS: The baseline data for this prospective cohort study were
      collected in 1971--1975 for the first National Health and Nutrition Examination
      Study (NHANES I) and 1976--1980 as part of the second NHANES (NHANES II) with
      mortality follow-up using the National Death Index (NDI) through December 31,
      1992. The main analyses were the relative risks of total mortality and cause
      specific mortality for persons who used aspirin compared to persons who did not
      use aspirin adjusted for confounding using Cox proportional hazards. RESULTS: The
      proportion of aspirin users was lower among cancer cases than non-cases (58%
      versus 66%) and use of aspirin decreased with age. Consequently, age was a
      negative confounder attenuating the protective association between aspirin use
      and cancer and cardiovascular mortality. After adjusting for age, BMI, sex, race,
      poverty index, education and smoking, we observed a significant association of
      reduced all cause mortality among all aspirin users (relative risk [RR] = 0.88;
      95% confidence interval [CI] 0.85 - 0.99) and lung cancer mortality among male
      aspirin users (RR = 0.69; CI 0.49-0.96). However, for women we observed adverse
      associations between aspirin use and bladder (RR=12.31; CI 2.98-50.80) and brain
      cancer mortality (RR=3.13; CI 1.09-9.00), although case numbers were small.
      CONCLUSION: Aspirin use appears to offer protection from all causes of mortality
      and lung cancer among men. In women aspirin use is associated with increased risk
      of bladder and brain cancer. Because of the small number of female bladder (n=15)
      and brain (n=20) cancer cases in this cohort the findings require confirmation.

PMID- 15510609
TI  - Extended intestinal metaplasia. A survey of 1392 gastrectomies from dwellers of
      the Pacific basin.
AB  - BACKGROUND: To assess the extent of gastric intestinal metaplasia (IM) in
      gastrectomy specimens in populations of the Pacific basin having different
      incidence of gastric carcinoma. MATERIALS AND METHODS: One thousand three hundred
      and nine-two gastrectomies were investigated: 1088 had a gastric carcinoma and
      304 miscellaneous gastric diseases. Twenty-one thousand three hundred and
      fourteen histological sections were reviewed under low-power (4X). IM was either
      spotty (SIM) or extended (EIM= encompassing one or more entire low-power
      fields/section). Widespread IM (WIM) was regarded as EIM if present in > or =5
      histological sections. RESULTS AND CONCLUSION: The percent of gastrectomies
      harboring a carcinoma increased significantly with increasing age more notably in
      those with diffuse carcinomas (DC) than in those with intestinal carcinomas (IC).
      The percent of gastrectomies with EIM was significantly higher in specimens with
      IC than with DC, particularly among elderly patients, and in specimens from
      countries with a high cancer incidence. The percent of gastrectomies with WIM was
      higher in specimens having IC than in those having DC. Migration per se did not
      influence the frequency of specimens with EIM in elderly Japanese patients:
      Japanese migrants to Hawaii had a similarly high frequency of EIM as those
      dwelling in Japan. Japanese patients with a gastric carcinoma showed atypical
      mitoses in areas with EIM far from the tumor, suggesting that cellular
      mutation(s) play a role in the evolution of EIM towards gastric dysplasia and
      carcinoma in that ethnic group. The drawback of gastric biopsies in assessing the
      extent of gastric intestinal metaplasia and, thereby, estimating possible cancer
      risk in long-term studies has been stressed.

PMID- 15510610
TI  - Comparison of bone scintigraphy with bone markers in the diagnosis of bone
      metastasis in lung carcinoma patients.
AB  - This study was designed to evaluate the utility of the bone markers total
      alkaline phosphatase (TAP), bone-specific alkaline phosphatase (BAP),
      aminoterminal propeptide of type I collagen (PINP), carboxyterminal propeptide of
      type I collagen (PICP), pyridinoline crosslinks (PYD), deoxypyridinoline
      crosslinks (DPD), cross-linked carboxyterminal telopeptide of type I collagen
      (ICTP), cross-linked carboxyterminal telopeptide of type I collagen (CTx, beta
      CrossLaps) and tartrate-resistant acid phosphatase 5b (TRAP 5b) in comparison
      with bone scintigraphy for the diagnosis of bone metastasis in lung carcinoma
      patients. The study population consisted of 49 patients with bone metastasis
      confirmed by plain radiography and/or computed tomography, 89 patients without
      bone metastasis, 12 patients with benign lung diseases and 18 healthy persons.
      All patients were of male gender. The bone markers were measured using
      commercially available tests. Serum and urine were collected from fasting
      patients at the time of bone scan between 7.00 and 8.00 a.m. The sensitivity of
      bone scintigraphy was 100%, its specificity 76.4%, resulting in a diagnostic
      efficiency of 84.8%. The positive predictive value was calculated to be 70% and
      the negative one to be 100%. The concentrations of the bone markers TAP, BAP,
      PINP, PYD, DPD and ICTP were significantly higher in patients with bone
      metastasis than in those without bone metastasis (p<0.01). The levels of PICP and
      CTx only tended to be higher in the patients with bone metastasis compared to
      those without bone metastasis. There was no significant difference in the TRAP 5b
      levels between the two groups. There was also no difference in the marker levels
      between osteoblastic, osteolytic and mixed osteoblastic-osteolytic lesions.
      Contrary to BAP, PICP, CTx and TRAP 5b, the markers TAP, PINP, PYD, DPD and ICTP
      were found to be higher (p<0.01-0.05) in patients with bone metastasis than in
      patients with benign lung diseases. In addition, PYD, DPD and ICTP differentiated
      patients with benign lung diseases from the healthy controls. Based on cut-off
      values that correspond to 95% specificity in the group of healthy persons, the
      sensitivity of the marker assays were as follows (specificity in brackets): TAP
      33.3% (97.5%), BAP 22% (100%), PINP 18.4% (97.5%), PICP 2.1% (95.2%), PYD 91.8%
      (24.1%), DPD 83.7% (34.5%), ICTP 75.5% (44.6%), CTx 45.8% (77.5%) and TRAP 5b 14%
      (84%). The corresponding data for the diagnostic efficiency were as follows: TAP
      73.6%, BAP 77.1%, PINP 67.7%, PICP 61.1%, PYD 48.5%, DPD 55.2%, ICTP 56.1%, CTx
      65.6% and TRAP 5b 58.7%, respectively. The positive predictive values ranged from
      20% (PICP) to 100% (BAP) and the negative values from 62.7% (PICP) to 84% (PYD).
      In the ROC analysis, TAP, followed by RAP, PINP and PYD, showed the best
      performance. The levels of TAP, BAP, PINP, PYD, DPD and ICTP were found to be
      higher in the patients with bone metastasis compared to those with metastastic
      lesions in other sites (p<0.01, except for ICTP having a p value of < 0.05). The
      levels of TAP, BAP, PYD, DPD and ICTP increased significantly with the number of
      metastases. There was also a steady increase in T scores of the markers PINP,
      PYD, DPD and ICTP with the extent of the metastatic bone disease. It is concluded
      that the currently available bone markers cannot replace bone scintigraphy,
      either for screening or in the diagnosis of bone metastasis, in lung carcinoma
      patients. However, a panel consisting of TAP, BAP, PINP, PYD, DPD and ICTP may be
      of some value as an adjunct tool to bone scintigraphy for this purpose.

PMID- 15510611
TI  - Cytokeratin positivity in paraffin-embedded malignant melanomas: comparative
      study of KL1, A4 and Lu5 antibodies.
AB  - The unclear role of cytokeratin (CK) in the progression and diagnostics of
      malignant melanomas stimulated us to compare the reactivity of three antibodies
      directed to CK in 109 paraffin-embedded melanomas. By far the majority of
      melanomas did not express cytokeratin even at the<1% level, only vimentin. In
      about 6% of melanomas it was possible to find CK expression ranging between 3 and
      40% of melanoma cells. There was a correlation between CK expression and pT
      stage. Cytokeratin-expressing tumours were found in the more advanced pT-stages.
      The independent prognostic values of none of the three CK antibodies investigated
      could be shown.

PMID- 15510612
TI  - Effect of primary anthracycline-based chemotherapy on disseminated tumor cells in
      locally advanced breast cancer.
AB  - BACKGROUND: The leading cause of death from epithelial cancer is metastatic tumor
      relapse due to early dissemination of tumor cells. In this study we investigated
      the elimination rate of disseminated tumor cells in bone marrow and the clinical
      response under primary chemotherapy in locally advanced breast cancer. PATIENTS
      AND METHODS: Thirty patients underwent primary anthracycline-containing
      chemotherapy for breast cancer. For immunocytochemical tumor cell detection in
      bone marrow, the monoclonal antibody 5D3 was used. RESULTS: At time of diagnosis,
      10/30 (33%) patients had cytokeratin-positive tumor cells in bone marrow. After
      primary and chemotherapy, 8/30 (27%) patients still tested positive. Clinical
      complete response (cCR) was observed in 5/30 (17%) patients partial response
      (cPR) in 12/30 (40%) patients, resulting in an overall rate of clinical response
      to primary chemotherapy in 57%. CONCLUSION: Primary chemotherapy in breast cancer
      is effective regarding the reduction of tumor size but seems incapable of
      reducing the burden of disseminated tumor cells in bone marrow.

PMID- 15510613
TI  - Methylenetetrahydrofolate reductase and thymidylate synthase polymorphisms are
      not associated with breast cancer risk or phenotype.
AB  - BACKGROUND: Aberrations in folate metabolism contribute to the risk of cancer via
      effects on the synthesis, methylation and repair of DNA. Functional genetic
      variants in the methylene tetrahydrofolate reductase (MTHFR) and thymidylate
      synthase (TS) genes may be risk factors for breast cancer because of their
      central roles in cellular folate metabolism. PATIENTS AND METHODS: The MTHFR
      C677T and TS tandem repeat polymorphisms were investigated in a case-control
      study of 339 women with breast cancer for possible associations with the risk of
      this disease, tumor phenotype and patient survival. RESULTS: The MTHFR and TS
      polymorphisms were not associated with a significantly increased risk of breast
      cancer. No associations were observed with any pathological or molecular feature
      and neither polymorphism was associated with survival from this disease.
      CONCLUSION: The common MTHFR C677T and TS enhancer region polymorphisms were not
      risk factors for breast cancer in this patient cohort nor were they associated
      with phenotypic features or with prognosis.

PMID- 15510615
TI  - P21WAF1/CIP1 protein and tongue cancer prognosis.
AB  - The expression of the cell cycle regulatory protein p21waf1/cip1 was analyzed
      immunohistochemically in tissue from the tumor and adjacent non-tumor epithelia
      of 54 patients with tongue cancer in order to determine the proportion of tongue
      carcinomas with altered p21waf1/cip1 expression, establish whether this
      alteration is an early event in tongue carcinogenesis and to investigate whether
      p21waf1/cip1 expression has predictive prognostic value in these tumors. The
      percentage of p21waf1/cip1-positive neoplastic cells was calculated. Adjacent non
      tumor epithelium was classified as normal, hyperplastic or dysplastic, and the
      p21waf1/cip1 expression was only considered normal in suprabasal layers.
      P21waf1/cip1 expression was negative in 57.4% (31/54) of the tumors and was
      aberrant in the non-tumor adjacent tissue of all patients studied. Neither the
      absence nor the degree of p21waf1/cip1 expression influenced the survival of
      patients in the present series. P21waf1/cip1 system alteration may be an early
      and frequent event in tongue carcinogenesis.

PMID- 15510614
TI  - Relationship between tumor markers CEA and CA 15-3, TNM staging, estrogen
      receptor rate and MIB-1 index in patients with pT1-2 breast cancer.
AB  - BACKGROUND: The aim of this study was to analyze whether a correlation exists
      between preoperative serum tumor markers (STM) CEA and CA 15-3, age of the
      patients, TNM staging, hormone receptor (ER, PgR) status, and MIB-1 proliferation
      index in patients who underwent surgery for primary breast cancer (BC). PATIENTS
      AND METHODS: Data regarding a series of 255 consecutive women (median age 60
      years, range 30-85) with pT1-2 BC were reviewed, while patients with confirmed
      pT3-4 BC were excluded. All patients underwent preoperative CEA and CA 15-3 serum
      levels measurement, and the removed tissue was routinely processed for the
      detection of ER, PgR, and MIB1 index. RESULTS: Serum CEA and CA 15-3 measurements
      were above the cut-off in 44 (17.2%) and 75 (29.0%) patients, respectively, and
      the overall sensitivity of STM was 37.6%. A strong correlation between ER and PgR
      rate (R=0.77) was found. There was no relationship (p=NS) between age of the
      patients, size (R=0.08), MIB-1 index (R=0.11), and both ER (R=0.01) and PgR
      (R=0.03) rate. No linear correlation was found between both CEA and CA15-3 and
      the other variables, except for CA 15-3 vs. tumor size, which showed a mild
      (R=0.57) linear relationship. Tumor size, ER rate, and the number of positive
      nodes were significantly (p <0.01) different between patients with CA 15-3 values
      normal and above the cut-off. Comparing the subgroup of patients with CA 15-3
      above the cut-off and CEA within normal values (Group 1) versus patients with CA
      15-3 within normal values and CEA above the cut-off (Group 2), a significant
      difference was found in the tumor size (Group 1: 28.3+/-9 mm; Group 2: 17.9+/-7.5
      mm; p<0.0001) and in the number of positive nodes (Group 1: 2.2+/-3.3; Group 2:
      0.5+/-1.5; p<0.01). Finally, CA 15-3, but not CEA, showed a significant
      correlation with the tumor grading (p<0.0001). CONCLUSION: In patients with BC,
      STM correlate exclusively with the size of the tumor. Both have low sensitivity
      and no significant relationship with other prognostic factors. Thus, preoperative
      serum tumor markers measurements are of little value, especially in patients with
      early-stage BC, and are not useful in the therapeutic decision-making of patients
      with BC.

PMID- 15510616
TI  - Lack of HER-2/neu overexpression in non-Hodgkin's lymphoma.
AB  - OBJECTIVES: The HER-2/neu oncogene is overexpressed in many types of cancer and
      especially in 25% to 30% of breast cancers. Single reports mention HER-2/neu
      positivity in hematological malignancies like Hodgkins's disease and even diffuse
      large-cell lymphoma. OBJECTIVE: To test for HER-2/neu overexpression in patients
      with non-Hodgkin's lymphoma and the possible role of the recombinant monoclonal
      anti-HER-2/neu antibody trastuzumab (Herceptin) in the treatment of non-Hodgkin's
      lymphoma. MATERIALS AND METHODS: Serum samples from 87 consecutive unselected
      patients with non-Hodgkin's lymphoma were retrospectively retrieved from a serum
      bank and tested for the shed antigen of HER-2/neu using the Oncogene Sciences
      ELISA assay (Cambridge, MA, USA). From those lymphoma patients, the paraffin
      embedded lymph-node specimens of 25 cases with diffuse large-cell lymphoma were
      stained with the HER-2/neu DAKO HercepTest. RESULTS: In 87 lymphoma patients, the
      serum level of HER-2/neu ranged from 3.6 to 244.1 ng/ml (median 8.0 ng/ml). Only
      2 patients showed a marginal or increased HER-2/neu level with 15 ng/ml (which is
      the upper limit of normal) and 244.1 ng/ml, respectively. No patient with diffuse
      large-cell lymphoma showed HER-2/neu overexpression by immunhistochemistry of the
      lymph node. The paraffin block of the one patient with a very high HER-2/neu
      serum level was also stained for HER-2/neu overexpression. In this patient,
      suffering from a high-grade T-cell non-Hodgkin's lymphoma, no staining could be
      found. CONCLUSION: HER-2/neu is not overexpressed in non-Hodgkin's lymphoma and
      especially not in diffuse large-cell lymphoma, using a standardized
      immunochemistry technique with complementary serum testing. Thus, specific anti
      HER-2/neu-targeted therapy should play no role in the treatment of non-Hodgkin's
      lymphoma.

PMID- 15510617
TI  - Conformal hypofractionated and accelerated radiotherapy with cytoprotection
      (HypoARC) for high risk prostatic carcinoma: rationale, technique and early
      experience.
AB  - Recent radiobiological analysis of the radiotherapy results for prostate cancer
      revealed that prostate carcinoma behaves as a late responding tissue, sharing an
      alpha/beta ratio lower than 2Gy. These findings suggest that hypofractionation
      may be more effective. Reduction of the overall treatment time could further
      increase response by abrogating the effect of rapid tumor repopulation. In the
      present study we report a conformal technique applied (to pelvis and prostate)
      for the treatment of high-risk prostate cancer, using hypofractionated and
      accelerated radiotherapy (3.4Gy x 15 consecutive fractions) supported with high
      dose daily amifostine (1000mg subcutaneously) to protect normal tissues against
      early and late effects. The biological dose delivered to the prostate cancer by
      this HypoARC (hypofractionated accelerated radiotherapy with cytoprotection)
      technique is estimated to be 71.4Gy (alpha/beta= 1.5 Gy). The time-adjusted
      biological dose is estimated to 77-94 Gy. Amifostine tolerance was excellent. All
      seven patients recruited up to now have accomplished their treatment with grade 0
      1 cystitis or diarrhoea (5/7 grade 0). The study is ongoing to assess efficacy
      and late effects of HypoARC.

PMID- 15510618
TI  - Serum markers as predictors of esophageal squamous dysplasia and early cancer.
AB  - BACKGROUND: Squamous dysplasia is the precursor lesion for esophageal squamous
      cell carcinoma (ESCC). A primary screening test for ESCC which identified this
      lesion could lead to a reduction in disease-specific mortality. MATERIALS AND
      METHODS: We conducted a population-based screening study in Linzhou, China. All
      subjects provided blood samples and underwent endoscopy with Lugol's iodine
      staining and biopsy. We selected a subset of 84 subjects stratified on worst
      squamous histologic diagnosis in six categories and measured the serum
      concentrations of potential markers using commercially available ELISA tests for
      matrix metalloprotease-9, tissue inhibitor of matrix metalloprotease-1,
      copper/zinc superoxide dismutase, anti-p53 auto-antibodies, and soluble serum
      interleukin-2 receptor. RESULTS: Serum matrix metalloprotease-9 concentration was
      significantly different by esophageal squamous dysplasia status with a median
      (interquartile range) for subjects without dysplasia of 150 ng/ml (80-225) and
      subjects with dysplasia/early cancer of 97 ng/ml (58-155), p=0.033), but the
      maximum sensitivity and specificity were low. The serum concentrations of the
      other markers tested showed no significant differences by category of worst
      histologic diagnosis. CONCLUSION: Serum matrix metalloprotease-9 concentration
      could contribute to a primary screening test for an ESCC, but is insufficient
      alone.

PMID- 15510619
TI  - Immunocompetence in non-seminomatous testicular cancer patients before any
      treatment and one year after completion of therapy.
AB  - BACKGROUND: Assessment of immunocompetence in non-seminomatous testicular cancer
      (NSTC) patients. MATERIALS AND METHODS: In the peripheral blood of 43 patients
      with NSTC, lymphocyte subsets, lymphocyte reactivity to mitogens, NK cell
      activity as well as neutrophil and monocyte phagocytic functions were studied.
      RESULTS: The proportion and number of T- and B- lymphocytes, lymphocyte
      reactivity to mitogens as well as neutrophil and monocyte phagocytic functions
      were equal in patients with localized disease and in those with metastatic
      disease and they not differ from those in controls. The NK cell number and NK
      cell activity, however, were significantly impaired in both patient groups. The
      patients with metastatic disease had a lower NK cell activity than those with
      localized disease. One year after the completion of anticancer treatment, the NK
      cell number and cytotoxic activity recovered in both groups of patients.
      CONCLUSION: These results suggest that patients with NSTC are primarily deficient
      in NK cell number and their cytotoxic function influence the host's ability to
      control the proliferation and spread of tumor cells.

PMID- 15510621
TI  - Outcome of local application of amifostine (WR-1065) on epirubicin-induced oral
      mucositis. A phase II study.
AB  - BACKGROUND: Intravenous administration of amifostine reduces chemotherapy-induced
      toxicity. Preclinical experiments showed a reduction in radiation-induced
      mucositis after local application of the active metabolite of amifostine (WR
      1065). This study evaluated the effect of local application of WR-1065 on
      chemotherapy-induced oral mucositis. PATIENTS AND METHODS: Non-small cell lung
      cancer patients treated with gemcitabine and epirubicin every 3 weeks for a
      maximum of five cycles were included. WR-1065 was administered during the second
      and third cycle as an oral rinse. Oral mucositis evaluation included WHO toxicity
      grading, a validated oral mucositis assessment scale (OMAS) and a questionnaire.
      RESULTS: Twenty-four patients were evaluated for at least one control and one
      rinse cycle. Mucositis scores, pain and feeding difficulties increased from day 1
      to day 15, and were not significantly different between the control and rinse
      cycles. Local application of WR-1065 leads to detectable quantities of WR-1065 in
      epithelial mucosa cells. A negative correlation between the WR-1065 concentration
      and OMAS score was found. CONCLUSION: No clinical detectable influence of WR-1065
      on oral mucositis was found.

PMID- 15510620
TI  - Long-survival in responding patients with metastatic breast cancer treated with
      doxorubicin-docetaxel combination. A multicentre phase II trial.
AB  - BACKGROUND: The doxorubicin-docetaxel combination is active in breast cancer; the
      aim of the present study was to evaluate the complete response rate and safety
      profile of the doxorubicin and docetaxel regimen as first-line chemotherapy in
      metastatic breast cancer patients. PATIENTS AND METHODS: Forty-three patients
      entered the study. Treatment plan was: doxorubicin (50 mg/m2, i.v. bolus)
      followed 1 hour later by docetaxel (75 mg/m2 i.v. infusion over 1 hour), q 3
      weeks, for up to six courses. The patients achieving a response or a
      stabilisation of disease after 6 courses were allowed to intensify the treatment
      with docetaxel (100 mg/m2, q 3 weeks) for up to 2 courses. G-CSF (or GM-CSF) was
      administered if clinically indicated. RESULTS: Patients' median age was 57years
      (range 32-75) and 72% of them had visceral disease. A total of 217 doxorubicin
      docetaxel courses were delivered, with 70% of patients receiving all the 6
      planned cycles. Among the 40 patients assessable for response (WHO criteria), 7
      (16%) achieved a complete remission and 22 (51%) a partial remission, for an
      overall response rate (intent-to-treat) of 67% (95% C.I. =53% to 81%). In 19
      patients, the treatment was intensified with two more single-agent docetaxel
      cycles, without ameliorating the response. Twenty-seven patients with oestrogen
      receptor-positive received hormonal therapy as 'maintenance' after completing
      chemotherapy treatment. NCIC G3-G4 neutropenia was recorded in 58% of patients,
      with G/GM-CSF used in 23 (53%) patients and 91 (38%) cycles. No patients
      experienced severe cardiac or neurological toxicity. No toxic death occurred.
      With a median follow-up of 41 months among alive patients, we observed in
      responder patients an overall median time to progression and survival of 18 and
      33 months respectively, with ten long-survivors still alive. CONCLUSION: This
      study confirmed the combination doxorubicin-docetaxel as a very active regimen
      for metastatic breast cancer. Remarkably long survival times were observed not
      only in complete responders, but also in those patients who responded partially.
      This might be equally attributed to first-line treatment and sequential
      maintenance hormonal therapy.

PMID- 15510622
TI  - Centrosomes--their role in tumors and cancer therapy.
AB  - The centrosome is a small organelle located near the nucleus which acts as the
      microtubule organizing center for the cell. Abnormalities in centrosome
      replication resulting in centrosome amplification have been identified in most of
      the common human cancers and implicated in the development of genetic instability
      and cancer. Research in centrosomes is evolving rapidly with identification of
      key regulatory proteins. This knowledge could help to explain the mechanisms of
      action of existing cancer treatments and also lead to the development of new
      molecularly-targeted therapy.

PMID- 15510623
TI  - Multicenter pilot study of 5-fluorouracil, folinic acid, interferon alpha-2b and
      degradable starch microspheres via hepatic arterial infusion in patients with
      nonresectable colorectal liver metastases.
AB  - BACKGROUND: It is necessary to establish therapeutic regimens for patients with
      nonresectable hepatic metastases of colorectal carcinoma. A new regional
      chemotherapy regimen was tested in a prospective study in three centers. PATIENTS
      AND METHODS: An arterial port system was implanted in 95 patients. From January
      1994 to March 1999, intra-arterial treatment was applied via the hepatic artery
      using 450 mg starch microspheres with 5 million IU recombinant interferon-alpha
      2B, 500 mg/m2 folinic acid and 600 mg/m2 5-FU body surface for 5 days with a 14
      day interval. RESULTS: The tumor response rate was 70%. Median disease
      progression was 17 months, median survival 24 months. The subgroup analysis shows
      a significant advantage (p<0.00001) for patients with a liver tumor involvement
      of <25% and a median survival of 39 months compared to a tumor involvement of 25
      50% (24 months) and >50% (14 months). Major toxicity problems were observed in
      11%. However, there was no termination of therapy on account of these problems.
      CONCLUSION: Intra-arterial chemotherapy with our new regimen was useful in
      patients with colorectal liver metastases who had only an intrahepatic tumor
      burden of <50%.

PMID- 15510624
TI  - Analysis of correlation between mitotic index, MIB1 score and S-phase fraction as
      proliferation markers in invasive breast carcinoma. Methodological aspects and
      prognostic value in a series of 257 cases.
AB  - BACKGROUND: The study was designed in order to evaluate the degree of correlation
      of mitotic index (MI), Ki67 (MIB1) score and S-phase fraction (SPF) as markers of
      cell proliferation and prognosis in breast cancer. MATERIALS AND METHODS: The
      series analysed corresponded to 257 consecutive invasive breast carcinoma,
      treated at the Institut Curie, France, in 1995. Nottingham histological grade and
      MIB1 semiquantitative and quantitative score were assessed on histological
      sections, whereas SPF was calculated using flow cytometry analysis of fine-needle
      aspiration products. Proliferation indices were compared to pathological data and
      to overall survival (OS) and disease-free survival (DFS) (minimum follow-up: 72
      months). RESULTS: The median values for the proliferation markers were 9/10 HPF
      for MI, 32.4% for MIB1 and 3.7% for SPF. A high rate of correlation (r=0.96;
      p<0.001) was observed between semi-quantitative and quantitative MIBI evaluation.
      A positive correlation was found between the three markers (r ranging from 0.54
      to 0.61;p<0.001). Univariate analysis of markers associated to disease outcome
      showed that MIB1, axillary node status (N) and progesterone receptor (PR) status
      were significantly associated with OS and that MIB1 and SPF were associated with
      DFS, together with node and hormone receptor status. In multivariate analysis,
      when proliferation markers were adjusted on the N and PR status, only MIB1
      retained a prognostic value for OS (RR= 1.83) [1.00;3.35] and SPF for DFS (RR=
      1.58) [1.02-2.44] (p=0.04). CONCLUSION: A good level of correlation was observed
      between the values of the three markers of tumour cell proliferation analysed. In
      this series of invasive breast cancers, MIB1 immunostaining was found to be a
      prognostic marker of both OS and DFS. The median (32.4%) was a valuable cut-off
      value for prognostic assessment. Semi-quantitative and quantitative evaluations
      provided very similar values. MIB1 can thus be considered as a reliable
      prognostic maker, usable in small size tissue specimens which are inappropriate
      for MI or SPF analysis. The impact of MIB1 compared to that of the other
      proliferative markers will be further assessed in a subgroup of T1N0M0 for which
      the prognostic assessment is of major interest.

PMID- 15510625
TI  - [The classification and treatment of lamina papyracea blow-out fracture].
AB  - OBJECTIVE: To investigate the classification criterion and the treatment of
      lamina papyracea blow-out fracture. METHOD: A clinic analysis was made on 108
      case with lamina papyracea blow-out fracture. According to the classification,
      different treatments were taken differently. RESULT: The classification of 108
      cases were reported as follows: 71 cases were classified as level 1, 33 cases as
      level 2, 4 cases as level 3. There was no special treat-ment for 43 cases (level
      1) who had no diplopia. 28 cases (level 1) who had symptom of diplopia were
      treated conservatively. Its cure rate was 92. 9% (26/28). Other 34 cases were
      operated. Among them, 33 cases were classified as at least level 2, 1 case who
      had no satisfactory curative effect with conservative therapy was classified as
      level 1. The cure rate was 88. 2% (30/34). The other 4 cases classified as level
      2 or 3 who didn't accept operation were treated conservatively, the cure rate was
      25% (1/4). CONCLUSION: The classification of lamina papyracea blowout fracture
      facilitates the judgement of patient's condition and the selection of treatment.
      The transnasal endoscopic operation on serious lamina papyracea blow-out fracture
      cases produces a good curative effect.

PMID- 15510626
TI  - [Effect of salvagy surgeries for nasopharyngeal carcinoma].
AB  - OBJECTIVE: To explore a reasonable surgical method for improving salvagy surgery
      of nasopharyngeal carcinoma (NPC). METHOD: 25 cases of nasopharyngeal carcinoma
      with salvagy surgery were reviewed. Surgical accesses include the transcervico
      mandibuio-palatal, the maxillary swing approach, the transpalatal approach for
      removing nasopharyngeal lesion. The pectoralis major muscle flap and galea
      aponeurotica flap were employed to repair operative defect and protect the
      critical structure of parapharyngeal space and the skull base. RESULT: The
      operative complication rate is 16% (4/25), which are local infection and flap
      putrescence. The postoperative sequela such as cleft palate is slight. 18 cases
      were followed-up over 3 year and 8 cases died. 2 cases were lost. The 3-year
      survival rate is 44% (8/18). CONCLUSION: The best operation access should be
      selected depending on the position and the implicated scope. Safely and fully
      removal of the tumor and reliably reconstruct are necessary. It is possible to
      improve salvage surgery effect for NPC patients.

PMID- 15510627
TI  - [Treatment for chronic dacryocystitis by dacryocystorhinotomy with Ho: YAG laser
      under endoscope].
AB  - OBJECTIVE: To analyze the experience and curative effect in treating chronic
      dacrocystitis by dacryocystorhinotomy with Ho:YAG laser under endoscope. METHOD:
      20 patients of chronic dacryocystitis were treated by dacryocystorhinotomy with
      Ho:YAG laser under endoscope, followed-up for 1 approximately 2 years to observe
      the curative effects. RESULT: One was unplugged 8 months after the operation, six
      after 6 months, four after 4 months and nine after 3 months. No recidivations was
      found one year after the operation and the effective rate was 100%. There was no
      complications in all of the cases. CONCLUSION: The technique of
      dacryocystorhinotomy with Ho: YAG laser under endoscope overcomes the
      disadvantages of traditional method of operation.

PMID- 15510628
TI  - [Choice of the methods for inferior turbinectomy].
AB  - OBJECTIVE: To make clear the indications for each kind of inferior turbinectomy
      and to find out the best way of inferior turbinectomy. METHOD: The nasal
      resistances in pre-operation and post-operation were examined with rhinomanometer
      in 97 cases. The time of recovery, the symptoms remained and the complications
      after operation were recorded. RESULT: "Functional" inferior turbinectomy is
      characterized for its mild postoperation reaction, quick recovery and good
      therapeutic effect whereas the partial inferior turbinectomy is characterized for
      its serious reaction, bleeding and dryness after operation. CONCLUSION: There is
      a definite indication for each kind of inferior turbinectomy, but the indication
      of " functional" inferior turbinectomy is wide.

PMID- 15510629
TI  - [The correlation analysis of the reactive intensity of intradermal test for
      allergens and the concentration of specific IgE in serum].
AB  - OBJECTIVE: To explore the relationship between the reactive intensity of allergen
      intradermal test and the concentration of specific IgE (sIgE) in serum. METHOD:
      Intradermal test of six kinds of allergens was done in 192 cases of allergic
      rhinitis, including house dust, mite in powder and dust, poly mould, spring
      pollen, summer autumn pollen and Artemisia pollen. The serumic study of these
      kinds of allergens was also done with Pharmacia CAP system. RESULT: The total
      accordance rates of these six kinds of allergens with IgE in serum respectively
      are: house dust 65.93%, mite in powder and dust 68.1%, poly mould 55.6%, spring
      pollen 66.7%, summer autumn pollen 60.0% and Artemisia pollen 74.4%. The
      correlation index of them respectively are: house dust 0.4235 (P < 0.01), mite in
      powder and dust 0.4029(P < 0.01), poly mould 0.4932, spring pollen 0.3277 (P <
      0.05), summer autumn pollen 0.2412 (P > 0.05) and Artemisia pollen 0.5000 (P <
      0.01). CONCLUSION: The intradermal test of five kinds of allergens except for
      summer autumn pollen correlates with the concentration of IgE in serum.

PMID- 15510630
TI  - [Study on the expression of proto-oncogene eIF4E in laryngeal squamous
      carcinoma].
AB  - OBJECTIVE: To investigate the expression of the proto-oncogene eIF4E in laryngeal
      squamous cell carcinoma and its relationship with clinical pathology. METHOD:
      Sections of 37 samples of laryngeal squamous cell carcinoma (LSCC) and 10 samples
      of vocal cords polyp were analyzed with anti-eIF4E polyclonal antibody utilizing
      SP (Streptavidin Peroxidase) immunohistochemical technique. RESULT: All 37 LSCC
      samples overexpressed eIF4E in the tumors (eIF4E score: 30 approximately 210),
      whereas no staining was observed in 10 samples of vocal cords polyp (eIF4E score:
      0). There was a significant correlation between overexpression of protein eIF4E
      with T stage, N stage, histological grade, recurrence and the states of
      metastases (P < 0.01). It did not correlate with age, sex, and site of tumor (P >
      0.05). CONCLUSION: The eIF4E plays an important role on tumorgenesis,
      development, invasion and metastases of laryngeal squamous cell carcinoma. There
      was a correlation between the overexpression of protein eIF4E with TNM stage,
      histological grade, recurrence and metastases. eIF4E in the laryngeal squamous
      cell carcinoma can be considered as an independent prognostic factor and tumour
      molecular marker.

PMID- 15510631
TI  - [EGG used in laryngeal diseases].
AB  - OBJECTIVE: To analyze the EGG of laryngeal diseases and to evaluate the
      significance of Electroglottgrapihc waveform in the diagnosis of laryngeal
      diseases. METHOD: The computer multimedia program of Dr. Speech science for
      Windows was used to obtain the EGG parameters in 120 cases of vocal polyp, 42
      cases of vocal nodule, 21 cases of vocal cord paralysis, 42 cases of laryngeal
      cancer and 38 cases of Reinke's edema. The ECG parameters were analyzed. RESULT:
      The special abnormal changes in the waves of EGG were related to the formation
      (type, position and size ) of laryngeal disease. CONCLUSION: The changes of
      Electroglottgraphic waveform perform a quantitative and objective index to the
      diagnosis of the laryngeal disease.

PMID- 15510632
TI  - [Hypopharyngeal and cervical esophageal repairing].
AB  - OBJECTIVE: To explore the ways of repairing the hypopharyngeal and cervial
      esophageal breach postoperatively. METHOD: 6 kinds of operations in 29 patients
      with hypopharyngeal and cervical esophageal repairing were analyzed. RESULT: In 9
      patients laryngeal function reserved, 8 cases recovered their function of swallow
      and speech postoperatively. One received a laryngectomy in II stage for wrong
      swallow. In 20 cases without laryngeal function, 17 cases can swallow, but 3
      cases had fistula. The 1, 3 and 5 year survival rates were 92%, 64.7% and 46.2%
      respectively. CONCLUSION: The firsthand suture and pectoralis major myocutaneous
      flap were better for the hypopharyngeal repairing of the patients with laryngeal
      function. The glossus flap, laryngeal tissue flap, pectoralis major myocutaneous
      flap and gastric-pharyngeal tally are useful for the digestive canal
      reconstruction of the patients with laryngectomy.

PMID- 15510633
TI  - [Application of chlorophyll in the cervical lymph nodes dissection of laryngeal
      and hypopharyngeal carcinomas].
AB  - OBJECTIVE: To investigate the patterns of cervical lymph node metastases from the
      carcinomas of larynx and hypopharynx. METHOD: Chlorophyll solution was injected
      submucosally into some portions of the larynx and hypopharynx preoperately as a
      stain of lymphatic system to help conduct modified neck dissections in 50
      patiants with laryngeal or hypopharyngeal carcinomas. Searial sections were
      performed. RESULT: The cervical lymph nodes were stained into deep green with a
      color contrast to the ambient structures, which facilitated the operation of neck
      dissections and the distinction of lymph nodes. Pathologically positive lymph
      nodes found in 48% of all the cases. The metastases to level I and V were always
      associated with other levels. By statistical analysis, there was a higher
      metastaic rate in level II, III, and V (P < 0.01). Overal 1 occult metastases
      were recorded in 23.5% of No (clinically negative neck)cases. The involvement
      were located only at level II or III. CONCLUSION: For cN+ (clinically positive
      neck) patiants, upper and middle jugular vein nodes should be dissected
      necessarilly,and then appropriate selective neck dissections might be considerd
      according to the intraoperative findings. For the cN(o) cases with supraglottic
      or hypopharyngeal carcinomas, it is suggested ipsilateral or bilateral upper and
      middle jugular vein nodes be dissected according to the clinical status.
      Chlorophyll as a kind of safe and distinctive stain of lymphatic system can be
      injected preoperatively routinely.

PMID- 15510634
TI  - [Glossopharyngeal neuroutomy by improved retrosigmoid approach].
AB  - OBJECTIVE: To explore a surgical approach to improve the operation effect of
      glossopharyngeal neuralgia (GPN). METHOD: In 8 cases with GPN, the improved
      retrosigmoid approach was adopted to access the cerebellopontine angle for
      exposing the jugular foramen and its adjacent tissues so as to cut off the
      glossopharyngeal under microscope. The sensoryrizotomy of trigemlind nerve was
      also performed if there was a trigeminal neuralgia. RESULT: All the symptom of
      pain in 8 cases with GPN disappeared after operation with no complication
      occurred. There was no recurrence following-up for 2 approximately 7 years.
      CONCLUSION: By improved retrosigmoid approach, it is easy to explore the jugular
      foramen and cut off the glossopharyngea for treating GDN.

PMID- 15510635
TI  - [Surgical resection of infantile hemangioma of parotid gland].
AB  - OBJECTIVE: To seek an effective approach of treatment to infantile hemangioma of
      parotid gland. METHOD: Nineteen cases of infantile hemangioma of parotid gland
      were analyzed retrospectively. The operative methods were as follows: Superficial
      parotidectomy (15 cases), total parotidectomy(3 cases), superficial parotidectomy
      and inner hemangioma ligation in parotid(1 cases). The neck-nape shin flap
      repair(3 cases),"Dissection outside the false capsule" and facial nerve anatomy
      are applied in the operation. RESULT: Three cases showed a partial facial nerve
      paralysis after operation. One cases needed a blood transfusion (200 ml) in the
      operation. The follow up was beyond 1 year with excellent results. CONCLUSION:
      "Dissection outside the false capsule, facial nerve anatomy and the neck-nape
      skin flap repair are applied in the operation. These treatment methods are
      effective and radical. It is worthy of wide application".

PMID- 15510636
TI  - [Treatment of the sphenoid sinusitis with neuro-ophthalmologic syndromes].
AB  - OBJECTIVE: To analyze the diagnosis and the treatment of neuro-ophthalmologic
      syndromes caused by sphenoid sinusitis. METHOD: 5 cases with neuro-ophthalmologic
      syndromes caused by acute or chronic sphenoid sinusitis were reviewed, 3 of them
      were performed a sphenoidostomy and other two were treated by injecting
      antibiotics and steroid. RESULT: The surgery and antibiotics can relieve the
      headache. However, recovery of the neuro-ophthalmologic syndromes was inconstant.
      CONCLUSION: CT scan can provide an early diagnosis and differential diagnosis.
      The delayed surgery may be response for the unsatisfied treatment results.

PMID- 15510637
TI  - [The prognostic role of electromyography in vocal cord paralysis].
AB  - OBJECTIVE: To predict the recovery of vocal cord paralysis (VCP) by using
      electromyography (EMG). METHOD: The characteristics of EMG of 46 patients with
      unilateral VCP were assessed to determine the most useful factors in determining
      prognosis. The factors include the duration, amplitude, waveform morphology, root
      mean-square, and time interval. RESULT: A positive prognosis for laryngeal
      recovery was indicated when the following EMG features were present in the
      immobile vocal fold during voluntary tasks if EMG was performed during 6 months
      of the onset of VCP: normal motor unit waveform morphology; no electrical
      silence. This predictive rate is 76%. When the root-mean-square value is greater
      than 26 microV, the predictive rate is 80%. On the basis of the criteria, all the
      prognostic rate is 84%. CONCLUSION: The results support the concept that EMG
      record is valuable in determining prognosis performed during 6 months of the
      onset of VCP.

PMID- 15510638
TI  - [Affection on oxygen tension of the lens after vitrectomy].
AB  - PURPOSE: To measure the oxygen tension (PO2) in the rabbit vitreous and lens and
      to investigate the mechanism by which it is controlled, the affection on oxygen
      tension of the lens after vitrectomy was studied. METHODS: Using a fiber-optic
      oxygen sensor system, oxygen tension of the rabbit vitreous and lens was probed
      in vivo and oxygen permeability of posterior capsule was also measured on
      isolated rabbit lens. RESULTS: It was found that with agreement with previous
      study, PO2 is relatively high and the PO2 gradient is large in vitreous body
      close to the retina whereas more than 0.5 mm away from the retina the vitreal PO2
      is relatively low and the PO2 gradient is very shallow. Oxygen tension in the
      lens is asymmetric with the anterior being higher than the posterior and oxygen
      in the posterior lens being at the similar tension as the anterior vitreous
      behind the lens. The posterior capsule of the rabbit lens is relatively high in
      oxygen permeability. CONCLUSIONS: The vitreous body plays a key role in
      maintaining a low and stable level of oxygen in the lens. After vitrectomy oxygen
      tension in the lens may increase.

PMID- 15510639
TI  - [Study on relationship between leukocytes and early diabetic retinopathy].
AB  - PURPOSE: To explore the leukocytic functions in adhesion, stacking and causing
      microcirculatory disorder in retinal microvessels in early diabetic rats.
      METHODS: Sixteen healthy adult male Wistar rats were randomly divided into normal
      control group and 3 months group of diabetes (STZ) . We carried out morphological
      observations and CD45 (Leukocyte Common Antigen) monoclonal antibody
      immunohistochemical studies of the retinal digest preparations. RESULTS:
      Morphological changes including capillary varix, irregularity of capillary
      caliber, was found in the retinal blood capillaries in diabetic rats at 3 months.
      Further more, the expression of CD45 was significantly increased in the diabetic
      retinal microvessels, which were found leukocytes adhering and stacking.
      CONCLUSION: Changes of retinal microvessels can be found in STZ diabetic rats at
      3 months. The leukocytes were important in the onset and development of diabetic
      retinopathy (DR).

PMID- 15510640
TI  - [Implication of non-perforating deep sclerectomy with amniotic membrane
      implantation for primary open-angle glaucoma].
AB  - PURPOSE: To evaluate the efficacy of non-perforating deep sclerectomy (NPDS) with
      amniotic membrane implantation for primary open-angle glaucoma (POAG). METHODS:
      Fourteen cases (23 eyes) of POAG underwent NPDS with amniotic membrane
      implantation. NPDS was performed with a fornix-based conjunctival flap using 0.
      04% mitomycin C(MMC) under the scleral flap for 4 minutes. A 6 mm x 9 mm amniotic
      membrane was then placed under the scleral flap and sutured using 10-0 nylon.
      RESULTS: One month postoperatively, the intraocular pressure (IOP) was less or
      equal to 21 mmHg in 23 eyes, with a total success rate of 100%. After 3 months of
      follow-up for 20 eyes, the completely success rate was 90%, and the partly
      success rate was 100%. After 6 months of follow-up for 11 eyes, the completely
      success rate was 72.7%, the partly success rate was 100%, and the visual acuity
      had no significance between the pre-operation and post-operation. After 12 months
      of follow-up for 6 eyes, the success rate was 66. 7%. A good bleb formation was
      seen in the eyes and the IOP was controlled successfully. No serious complication
      was found in all eyes. CONCLUSION: Amniotic membrane is an effective and safe
      implantation material for NPDS.

PMID- 15510641
TI  - [Angiographic changes in optic disc and its surrounding choroid after contusion
      of optic nerve].
AB  - PURPOSE: To study the angiographic changes in the optic disc and its surrounding
      choroidoretina after optic nerve contusion with fundus fluorescein angiography
      (FFA), and indocyanine green angiography (ICGA). METHODS: Thirty patients (30
      eyes) with various degree of optic nerve damage caused by ocular contusion were
      examined with FFA and ICGA. (The choroidal rupture were excluded in this study).
      RESULTS: All patients present some abnormal angiography except one case. The main
      findings in FFA were hypofluorescein on quadrantal or entire disc in the early
      phase and leakage or persistent nonperfusion in the late phase. Meanwhile, the
      choroid surrounding disc was clearly delayed in its choroidal filling time. The
      retinal pigment epithelium (RPE) damage was observed over the localized
      abnormally perfused choroid. However, the RPE above the circular area around the
      disc which was hypofluorescein in ICGA showed no RPE damage in 9 cases. There are
      2 cases combined with branche retinal vein occlusion and 19 (63%) cases showed
      ischemic changes exactly on the location of so-called "water separating zone".
      The visual acuity was not more than 0.1 in 80% of the patients in this study.
      CONCLUSIONS: There is severe optic nerve lesion in the strong ocular contusion,
      in which the choroidal and retinal arterial circulation has also been seriously
      damaged. The FFA and ICGA should be conducted in time in order to judge the
      injury correctly and allow the clinician to better manage the cases.

PMID- 15510642
TI  - [Effects of advanced glycation end products and hypoxia on endothelin-1 secretion
      by bovine retinal microvascular pericytes].
AB  - PURPOSE: To investigate the effects of advanced glycation end products(AGE) and
      hypoxia on endothelin-1 (ET-1) secretion by cultured bovine retinal microvascular
      pericytes (BRPs). METHODS: BRPs were incubated with different concentrations of
      AGE (8, 32, 125 microg/ ml) for four days, hypoxia (10% O2, 5% CO2, 85% N2) for
      12, 24, 48 hours, respectively and AGE for 2 days firstly and then hypoxia for 48
      hours. Finally, ET-1 production was assessed in culture supernatants of BRPs
      under basal and stimulated conditions by radioimmunoassay. RESULTS: Hypoxia
      stimulated ET-1 production in a time-dependent manner in cultured BRPs. AGE could
      not induce the production significantly, but it could upregulate the effect of
      hypoxia on ET-1. CONCLUSION: These results suggested that AGE and hypoxia could
      regulate the ET-1 production in BRPs. ET-1 might be related to microvascular
      dysfunction in diabetes.

PMID- 15510643
TI  - [Comparitive study of the threshold variability between blue-on-yellow perimetry
      and white-on-white perimetry].
AB  - PURPOSE: To compare the threshold variability of blue-on-yellow (B/Y) perimetry
      with white-white(W/W) perimetry, and evaluate the reproducibility of B/Y
      perimetry. METHODS: The B/Y perimetry and W/W perimetry in the Octopus 101
      perimetry were used to examine the visual fields of 12 normal subjects (24 eyes),
      16 cases (32 eyes) of primary open angle glaucoma (POAG), and 7 cases (14 eyes)
      of suspected POAG respectively. The B/Y perimetry and W/W perimetry were repeated
      to examine within 2 weeks. The point by point threshold variability of the two
      perimetries were compared and analysed. RESULTS: The total mean threshold
      variability for B/Y perimetry (2.61 +/- 0.94) dB was greater than that for W/W
      perimetry (2.11 +/- 0.90) dB in all subjects, but it had no significance (P =
      0.6244). The total mean threshold variability for B/Y perimetry (2.07 +/- 0.54)
      dB was significantly greater than that for W/W perimetry (1.50 +/- 0.34) dB in
      normal subjects (P = 0.0006), while no significance was found in suspected POAG
      and POAG groups between the two perimetries (P = 0.0523 and 0.9371). The
      threshold variability in the areas of some eccentricities for B/Y perimetry were
      significantly greater than that for W/W perimetry in normal subjects and
      suspected POAG group, but no significance was found in POAG group for all
      eccentricities between the two perimetries. CONCLUSION: The threshold variability
      for B/Y perimetry was greater than that for W/W perimetry in normal subjects, but
      no significance was found in suspected POAG and POAG between the two perimetries.

PMID- 15510644
TI  - [Studies on prediction of visual function of vitreous opacity patients by Vernier
      hyperacuity tests].
AB  - PURPOSE: To evaluate the clinical value of visual function with vitreous opacity
      patients preoperatively. METHODS: The vernier acuity examining soft wear system
      was developed to detect the 14 cases (14 eyes) with vitreous opacity patients
      preoperatively. Two fixed targets and a movable target are shown on the computer
      screen. The examine was asked to adjust the position of the central target and
      the relationship between it and align them by using a track-ball. The computer
      automatically recorded the deviations of distances between the movable target and
      the specific one, and computed the average threshold of hyperacuity and its
      variance. Then the hyperacuity result and postoperative visual acuity were
      compared. RESULTS: Paired t-test showed that the difference between peroperative
      and postoperative vernier acuity thresholds was not significant (t = 0. 52, P =
      0. 612). The coefficient of correlation was 0. 85 (P < 0. 01). Neither was the
      threshold variance (t = 0. 431, P = 0. 674). The correlation coefficient was 0.97
      (P < 0.01). The correlation coefficient between preoperative hyperacuity
      threshold and postoperative visual acuity was -0.74 (P < 0.01), and that between
      preoperative threshold variance and postoperative visual acuity was -0.95 (P <
      0.01). Based on the preoperative vernier acuity threshold and its variance, the
      function of linear regression was Y = 0.943 - 0.000116THv - 0.00193SDv.
      CONCLUSIONS: Vernier acuity remains good consistency after vitrectomy, and it is
      one of the sensitive parameter in predicting the postoperative visual function
      for vitreous opacities.

PMID- 15510645
TI  - [Trabeculetomy combined with implantation of silicon rubber slice for intractable
      glaucoma].
AB  - PURPOSE: To investigate the lowering-pressure outcome and postoperative
      complications of trabeculectomy with implantation of silicon rubber slice for
      intractable glaucoma. METHODS: Sixty eyes with intractable glaucoma, including 12
      eyes with neovascular glaucoma, 14 eyes with aphakic or pseudophakic glaucoma, 4
      eyes with congenital glaucoma, 18 eyes with failed filtering surgery glaucoma and
      12 eyes with glaucoma secondary to trauma, were performed trabeculectomy with
      implantation of silicon rubber slice. The postoperative lowering-pressure outcome
      and complications also were observed. RESULTS: All patients were follow-up for 5
      to approximately 34 months ( mean, 18.3 months) . The postoperative intraocular
      pressure of patients was 17.30 to approximately 37.19 mmHg [mean, (23.36 +/-
      4.06) mmHg] at the last visit. Of 60 eyes, the postoperative intraocular pressure
      was below 21 mmHg in 38 eyes (63.3%), between 21 to 30 mmHg in 18 eyes (30%) and
      higher than 30 mmHg only in 4 eyes (6.7%). No serious complications and rejection
      related to implantation of silicon rubber slice occurred in this group during the
      follow-up period. CONCLUSION: Trabeculectomy combined with implantation of
      silicon rubber slice seems to be an ideal procedure for treatment of intractable
      glaucoma in developing countries, especially in vast country hospital in China,
      this surgery also can replace the expensive import drainage device implant
      (Molteno tube implant) therapy for intractable glaucoma.

PMID- 15510646
TI  - [Observation on clinical effects of panretinal coagulation for diabetic
      retinopathy].
AB  - OBJECTIVE: Observing and evaluating the clinical effects of panretinal
      photocoagulation with Argon laser for diabetic retinopathy. METHODS: According to
      the results of fundus fluorescence angiography (FFA), panretinal photocoagulation
      with Argon laser were performed on 143 eyes (87 cases) of diabetic retinopathy,
      including 79 eyes with preproliferative diabetic retinopathy eyes with
      proliferative diabetic retinopathy (PPDR), 64 (PDR). Examination about FFA,
      visual acuity and fundus condition were carried out before laser treatment and 3
      months after photocoagulation. The regular following up lasted for 6 months to 2
      years. RESULTS: Laser photocoagulation proved effective in 122 eyes (85.31%) with
      diabetic retinopathy, including 73 eyes (92.41%) with PPDR, 49 eyes (76.56%) with
      PDR. The visual acuity were improved in 32 eyes (23.38%), no changes in 87 eyes
      (60. 84%), decrease in 24 eyes (16.78%). No complication was found in all
      patients. CONCLUSIONS: Panretinal photocoagulation with Argon laser is a safe and
      effective method to control the condition of diabetic retinopathy.

PMID- 15510647
TI  - [Nd: YAG laser therapy for persistent pupillary membranes].
AB  - PURPOSE: To evaluate the clinical effects and surgical techniques of Neodymium
      yttrium, aluminum, garnet(Nd: YAG) laser therapy for persistent pupillary
      membranes. METHODS: Twenty-five patients (26 eyes) with persistent pupillary
      membranes were suffered to resection membranes. The energy of laser was adjusted
      according to the thickness and density of the membranes. The laser with the best
      cutting effects and lowest energy was selected to resection. All patients were
      followed up for 3 - 6 months after the operation. RESULTS: All patients were
      cured after one laser therapy. The corrected visual acuities were improved in
      different degrees. Three eyes were 0.6 - 0.7 (11.5%), 5 eyes were 0.8-0.9 (19.2%)
      and 18 eyes were > or = 1. 0 (69.2%). No complication was observed. CONCLUSION:
      The laser therapy for persistent pupillary membrane is an easy, safe and
      effective method only if the laser energy is appropriately selected, the focus is
      accurate and the operation is dexterity.

PMID- 15510648
TI  - [The diagnosis and treatment of traumatic carotid-cavernous fistula].
AB  - PURPOSE: To detect the value of digital subtraction angiography (DSA) and intra
      vessel embolism in diagnosing and treating traumatic carotid-cavernous fistula
      (TCCF). METHOD: 9 cases with TCCF characteristic of pulsating exophthalmos, who
      were checked by DSA and treated by detachable balloon technique, were analyzed
      retrospectively. RESULT: Carotid-cavernous fistula of these patients was observed
      with DSA and occluded with intra-vessel embolism successfully. The carotid artery
      remained unobstructed postoperatively. No severe complication was observed.
      CONCLUSION: DSA was one of the best ways to make a correct diagnosis of TCCF and
      intra-vessel embolism, to give a successful therapy.

PMID- 15510649
TI  - [Clinical analysis of 106 school-aged children with eye trauma].
AB  - PURPOSE: To detect the characteristics of school-aged children with eye trauma
      for giving an appropriate way of treatment and prevention. METHODS: One hundred
      and six cases (107 eyes) of school-aged children with eye trauma treated in our
      hospital in the last 7 years were analyzed retrospectively. RESULTS: The main
      causes of trauma were playing plastic guns, firecracker and fireworks, scissors,
      or needle. Hyphema by ocular contusion or penetrating wound of cornea were often
      observed. The visual acuity of 44. 9% traumatic eyes was lower than 0.05
      preoperatively and most of them (83.2%) recovered from blindness postoperatively.
      CONCLUSIONS: Eye trauma was severely harmful to school-aged children's eyes.
      Paying more attention to prevention and carrying out extensively popular
      education of eye protection were two important means to prevent children from
      injury.

PMID- 15510650
TI  - [A pilot study of bone marrow stromal cells intraocular transplantation in the
      S334 transgenic rats and Sprague-Dawley rats].
AB  - PURPOSE: To investigate the survival and differentiation of human bone marrow
      stromal cells (BMSC) intraocular transplantation in newborn S334 retinal
      degeneration transgenic rats and (Sprague-Dawley)SD rats. METHODS: Human bone
      marrow stromal cells line was grown on the adhesive substrate in the condition
      media including a-Modified Eagle medium (a-MEM)/10% fetal bovine serum. The
      experiments were divided into four groups: Group 1: BMSC + (Retinoid Acid) RA
      transplanted in S334 transgenic rats (n = 5); Group 2: BMSC transplanted in S334
      transgenic rats (n = 5); Group 3: BMSC + RA transplanted in SD rats (n = 5);
      Group 4: BMSC transplanted in SD rats (n = 5). 2 microl cell suspension (about 4
      x 10(4) cells) was injected into the vitreous space in the transgenic rats and
      normal SD rats at Postnatal 1 (P1) respectively. The right eyes were treated eyes
      and the left eyes were used as control. At P14 and P23, the rats were killed and
      enucleated for histological assays using plastic section. RESULTS: In Group 1,
      the transplanted cells were well survived. They could continue to differentiate
      and participate in late-stage retinal development. The number of inner nuclear
      layer increased. Moreover, the host retina increased their thickness, but
      photoreceptor cells were not rescued from transplant. In Group 2, at P14, the
      BMSC continue to differentiate toward their linage cell fate and formed into
      hemorrhage island structures with few neurons if RA was not applied. Group 3,
      BMSC could survive, migrate. The number of inner nuclear layer increased also. In
      Group 4, it revealed that host retina structures were disorganized and transplant
      cells formed atypical proliferating mass. CONCLUSIONS: This pilot experiment
      indicated that bone marrow stromal cells could survival, differentiate and
      participate in the retinal development after transplanted into vitreous space in
      the new born transgenic rats and SD rats. Histological assays showed that
      transplanted cells integrated with inner nuclear layer of host retina. Thus, bone
      marrow stromal cells may be a useful vehicle for auto- transplantation for the
      therapy of variety of retinal degenerative disorders.

PMID- 15510651
TI  - [Transcription changes of alpha A-crystallins gene during the development of
      retinal degeneration in Rd, Rds and C3H mouse].
AB  - PURPOSE: To determine the relationship between retinal alpha A-crystallins and
      the development of retinal degeneration in rd, rds and C3H mice. METHODS: Total
      retinal mRNA was prepared from the retina of (rd) retinal degeneration, (rds)
      retinal degeneration slow, C3H and control C3B mice during the progress of
      retinal degeneration (Post-natal 3, 4, 5, 6, 8 weeks). The retinal expression of
      alpha A-crystallins was determined by semi-quantitative reverse transcription
      polymerase chain reaction (RT-PCR) analysis. RESULTS: Expression of retinal alpha
      A-crystallins is rather stable in rd, rds and C3H mice during the progress of
      their retinal degeneration. The expression is also similar to that in normal C3B
      mice but different to that in Royal college of surgeons(RCS) rats. CONCLUSION:
      Retinal alpha A-crystallins may not involve in the course of RP in rd, rds and
      C3H mice. The molecular mechanism of RP in rd, rds and C3H may be different to
      that in RCS rat.

PMID- 15510652
TI  - [Research of corneal ectasia following laser in-situ keratomileusis in rabbits].
AB  - PURPOSE: To analyze the relationship of the intraocular pressure (IOP), central
      corneal thickness (CCT) and corneal ectasia in rabbits underwent laser in-situ
      keratomileusis (LASIK). METHODS: This random study comprised three groups: twenty
      eight eyes of white rabbits underwent-3D to -10D myopic LASIK, twelve eyes
      underwent 3D to 10D myopic LASIK, twelve eyes served as controls. The rabbits
      were examined mask under general anesthesia pre- and post-operation. We
      investigated CCT, curvature and corneal ectasia of the rabbit at difference IOP
      level after the operation. Then the corneal conformation of rabbits was analyzed
      by topography modeling system (TMS). The pathological changes of the rabbit
      corneas were observed. The effect of the corneal thickness and IOP are analysed
      by statistical methods. RESULTS: The IOP and CCT are significantly correlated
      with the corneal ectasia respectively (P < 0.001) and together (P < 0.05).
      Keratoconus patterns were detected in rabbits by keratoconus screening system,
      and the pathological character of keratoconus was also found. CONCLUSION: The
      ablation depth of cornea and high IOP had a significant effect on corneal ectasia
      after LASIK treatment for myopia respectively and together. It suggested that the
      over ablation quantity on cornea and high IOP were the main reasons for
      keratoconus after LASIK.

PMID- 15510653
TI  - [Probing of lacrimal passage on congenital dacryocystitis].
AB  - PURPOSE: To investigate the effects of probing of lacrimal passage on congenital
      dacryocystitis. METHODS: 474 consecutive infants with congenital dacryocystitis
      were treated with probing of lacrimal passage. The data were retrospectively
      analyzed. RESULTS: In 474 eyes, there were 360 and 122 eyes with or without
      membranous block respectively, and 356 (98.89%) and 107 eyes (85.25%) with or
      without membranous resistance were respectively cured with probing of lacrimal
      passage; there were 12 eyes with stenosis and 8 eyes (66.67%) were cured. In
      operation, 1 and 3 eyes were respectively suffered from subcutaneous edema and
      laceration of canaliculus, but there was no baby suffered from infection or
      asphyxia. CONCLUSIONS: The effects of probing of lacrimal passage were related to
      the causes of obstruction of lacrimal passage, and it is very important to
      scrupulously feel in probing lacrimal passage.

PMID- 15510654
TI  - [Nursing of children after strabismus operation].
AB  - PURPOSE: To improve nursing quality after general anesthesia in children with
      strabismus operation and prevent from accidents. METHODS: 136 children with
      strabismus operation under general anesthesia were observed and cared by the same
      nursing staff. Efficient managements were performed to cure postoperative
      complications. The nursing records were analyzed. RESULTS: In the study,
      glossocoma occurred in 1 case, asphyxiation in 2 cases, fever in 7 cases, pain in
      25 cases, vomiting without eating after awakening in 33 cases. One patient tore
      off the bandaging lint because of dysphoria. CONCLUSION: A careful preoperative
      and postoperative observation, early and predictive management of postoperative
      complications help the children with strabismus operation under general
      anesthesia to recover and prevent from the accidents.

PMID- 15510655
TI  - [Surgical treatment of laryngotracheal stenosis].
AB  - OBJECTIVE: To improve the curative effects of laryngotracheal stenosis. METHOD:
      Seventy patients treated for laryngotracheal stenosis on the different pathologic
      condition of the larynx and trachea were retrospectively reviewed. Different
      operative reconstruction methods were used accordingly. RESULT: Among 70
      patients, 65 (92.9) patients succeed in decannulation. The average course of
      usage of stent was 14.8 days, the average course from operation to decannulation
      was 82.0 days. CONCLUSION: The choice of surgical procedure must be decided on
      the pathologic conditions of the larynx and trachea. Eliminating the defect of
      the mucosa and reconstructing a wide enough airway was the key to improve the
      curative effect.

PMID- 15510656
TI  - [Pathological studies of vocal polyps and vocal nodes].
AB  - OBJECTIVE: In order to investigate the pathological differences and similarities
      of vocal nodes and vocal polyps. METHOD: 144 samples of vocal nodes and vocal
      polyps were examined by an experienced pathologist. RESULT: There were no
      significant statistical difference in short-term vocal nodes and vocal polyps. In
      long-term vocal nodes and vocal polyps, vocal nodes had thickened basal membrane,
      and abnormal keratinization of epithelium, vocal polyps had thin or discrete
      thickening of basement membrane, more pronounced edema, dilated vessels or growth
      of new blood vessels. CONCLUSION: It proved that vocal nodes and polyps are the
      result of "microtraumas" occurring at various phases of wound repair, thus
      accounting for the homogeneity and heterogeneity of histological and clinical
      manifestations.

PMID- 15510657
TI  - [Evaluating the clinical applications of CTVL in laryngeal carcinomas].
AB  - OBJECTIVE: To evaluate the clinical applications of computer tomography virtual
      laryngoscopy (CTVL) in laryngeal carcinoma. METHOD: 34 cases of laryngeal
      carcinomas and 5 cases of normal larynx were scanned by spiral CT and analyzed by
      computers. The virtual endoscopy findings of all patients were compared with
      those of fiber optical laryngoscopy and surgical findings. All the carcinomas
      were pathologically proved. RESULT: The visualization of normal anatomical
      structure in larynx on CTVL is the same as that of fiber optic laryngoscopy.
      Tumor local extension showed in CT virtual endoscopy is superior to that of fiber
      optic laryngoscopy. Images of early laryngeal carcinomas showed in CT virtual
      endoscopy is not so good as those of fiber optic laryngoscopy. CONCLUSION: CT
      virtual laryngoscopy is a good complement to fiber optic laryngoscopy.

PMID- 15510658
TI  - [Diagnosis and treatment of sever craniofacial compound injure].
AB  - OBJECTIVE: It is purpose to analysis the diagnosis and treatment of sever
      craniofacial compound injure. METHOD: The surgical method of reposition of bone
      fracture of 21 cases with sever craniofacial compound injure included transfacial
      wound (9 cases) and transmidfacial approach(4 cases) and craniofacial approach (4
      cases) and multi incision subperiosteum tunnel approach(4 cases). RESULT: In 16
      cases which been followed, the function of chew has been recovered. CONCLUSION:
      Sever craniofacial compound injures is a complicate emergention. Doctor must
      master comprehensive classified method of fracture and ability of diagnosis and
      attach importance to surgical reposition and technique of rigid internal
      fixation.

PMID- 15510659
TI  - [Evaluating the impact of human papilloma virus infection on prognosis of
      juvenile laryngeal papilloma].
AB  - OBJECTIVE: To evaluate the relationship between human papilloma virus (HPV) and
      pathological characteristics of juvenile laryngeal papillomas (JLP). METHOD:
      Using polymerase chain reaction protocol, we analyzed paraffin embedded tissue in
      25 cases of juvenile laryngeal papilloma and determined the HPV type. RESULT: A
      total HPV infection positive rate was 96%, and HPV11 positive rate was 56%, HPV6
      positive rate was 40%. None of all was positive for HPV16, 18, 33, 71% of
      patients need tracheotomy in HPV11 infection group, and 30% of patients need
      tracheotomy in HPV6 infecting group. The post-operation relapse rate in HPV11
      positive group was 86% ,and in HPV6-positive group was 40%. CONCLUSION: Juvenile
      laryngeal papilloma is associated with HPV11, HPV6 infection and we considered
      that HPV11 infection may be the important guideline of the evaluation of disease
      prognosis.

PMID- 15510660
TI  - [Relation between vascular endothelial growth factor expression and clinical
      pathological character in laryngeal squamous cell carcinoma].
AB  - OBJECTIVE: To approach the relation between vascular endothelial growth factor
      (VEGF) expression and clinical pathological character in laryngeal squamous cell
      carcinoma. METHOD: Immunohistochemical staining (SP) was used to evaluated the
      expression of VEGF and microvessel count (MVC) in tumor tissues from 87 patients
      with laryngeal squamous cell carcinoma. RESULT: VEGF immune response was mainly
      localized to the tumor cell cytoplasm, positive rate was 77%. In laryngeal
      squamous cell carcinoma, the wider the tumor invaded, the stronger VEGF
      expressed, the fewer the tumor invaded, the weaker VEGF expressed (P < 0.05); The
      lower the tumor differentiated, the stronger VEGF expressed, the higher the tumor
      differentiated, the weaker VEGF expressed (P < 0.05); The stronger VEGF
      expressed, the more MVC were (P < 0.01); The mean MVC in tumor tissues was
      obviously higher than that in surgical margin tissues (P < 0.01). CONCLUSION: In
      laryngeal squamous cell carcinoma, the expression of VEGF was markedly correlated
      with tumor stage and differentiation, was positively correlated with MVC. As a
      result, VEGF may have an important role in the progression of laryngeal squamous
      the carcinoma.

PMID- 15510661
TI  - [E-cadherin gene mutation in recurrent and metastatic carcinoma of larynx].
AB  - OBJECTIVE: To evaluate the role of E-cadherin gene in the process of recurrent
      and metastasis of laryngeal cancer and to investigate the metastatic mechanism of
      laryngeal cancer. METHOD: Exploration of exon 5 and exon 7 of the E-cadherin gene
      by polymerase chain reaction (PCR), SSCP in the laryngeal cancer. RESULT: In
      normal laryngeal tissues, there was no E-cadherin gene mutation. E-cadherin gene
      mutation occured only in the primary carcinoma with cervical metastasis and
      recurrent laryngeal carcinoma. The mutation rate were 67.71% and 28.57%
      respectively. E-cadherin gene mutation occured more frequently in advanced
      carcinomas than that in early ones. CONCLUSION: E-cadherin gene mutation with its
      functional suppression was one of the molecular mechanisms of the laryngeal
      metastasis. It is suggested that E-cadherin may be a valuable prognostic marker
      for the carcinoma of larynx.

PMID- 15510662
TI  - [Application of endoscopic telescope in the treatment of the juvenile onset
      recurrent respiratory papillomatosis].
AB  - OBJECTIVE: To evaluate the treatment methods of the juvenile onset recurrent
      respiratory papillomatosis. METHOD: Twelve patients with juvenile onset recurrent
      respiratory papillomatosis were treated from 1995 to 1999 by using endoscopy.
      RESULT: Among the 12 cases, 3 cases had no recurrence within one year follow-up
      and were decannulated,the other 9 cases had recurrence postoperatively, but the
      recurrence period got longer. CONCLUSION: It is demonstrated that endoscopic
      surgery is an ideal therapy for the treatment of juvenile onset recurrent
      respiratory papillomatosis.

PMID- 15510663
TI  - [The peri-operative cure of patients suffered allergic purpura before
      tonsillectomy].
AB  - OBJECTIVE: To explore the peri-operative cure of patients suffered allergic
      purpura before tonsillectomy. METHOD: To review the perioperative cure of 7 cases
      operated on tonsillectomy in retrospect. RESULT: 7 cases didn't bleed during peri
      operation and were discharged from hospital after recovery. CONCLUSION: The
      operation was arranged in allergic purpura catabasis and the acute inflammation
      controlled. The patients should avoid to contact all kinds of doubtful
      predisposition and were administered antihistamin, anti-inflammatory agent, drugs
      decreasing capillary permeability during peri-operation.

PMID- 15510664
TI  - [Clinical study on modified transpalatine radical operation for carcinoma of
      nasopharynx].
AB  - OBJECTIVE: To evaluate the method of transpalatine surgical treatment of
      carcinoma of nasopharynx (NPC). METHOD: The artery palatine major was protected
      and the resection domain of primary lesion of NPC was expanded by modified hard
      palatine incision. Preventive radiotherapy and routine chemotherapy was given
      after the operation. RESULT: Twelve patients were in our report, five of II stage
      and seven of III stage. In all cases, the incisions in hard palatine were healing
      by first intention after the operations. The patients were followed up for six
      months to five years. None case was found relapse or palatal fistula. They all
      can swallow and speech as normal. Sequelae of radiotherapy was not found.
      CONCLUSION: Without affecting the healing of the incision, expanding the
      resective domain of primary lesion of NPC is possible by modified hard palatine
      incision, and the occurrence of sequelae of radiotherapy can be reduced by giving
      preventive radiotherapy.

PMID- 15510665
TI  - [An experimental study on location and clinical application of recurrent
      laryngeal nerve in vagus nerve].
AB  - OBJECTIVE: To locate the recurrent laryngeal nerve fascicles in vagus and
      investigate the effect of latero-terminal neurorrhaphy to repair recurrent
      laryngeal nerve. METHOD: The method of dissection and acetylcholinesterase
      histochemical staining of neural fibers were used to locate the recurrent
      laryngeal nerve fascicles in vagus. Then 60 SD rats were divided into three
      groups. In experimental group right recurrent laryngeal nerve were incised and
      anastomosed to recurrent laryngeal nerve fascicles in vagus by means of latero
      terminal neurorrhaphy. In control group right recurrent laryngeal were incised
      and sutured immediately by means of end-to-end nerve anastomosis. In normal group
      rats were not treated by any elements. One to three months later, 10 rats from
      each group were examined for vocal cord movement and nerve regeneration by using
      fibrolaryngscope and nerve electrormyography. RESULT: The recurrent laryngeal
      nerve fascicles is in the medial-front segment of the vagus and its diameter is
      about one-fourth as large as the vagus. One months after operation, This effect
      of latero-terminal neurorrhaphy had significant difference compared with the
      control group (P < 0.05). Three months after operation, This effect of latero
      terminal neurorrhaphy had not significant difference compared with the control
      group (P > 0.05). CONCLUSION: The location of the recurrent laryngeal nerve
      fascicles in vagus provids important anatomical guideline for surgery. The latero
      teminal neurorrhaphy has a similiar treatment effect compared with end-to-end
      nerve anastomosis. This microsurgical technique provides a new method for
      repairing recurrent laryngeal nerve.

PMID- 15510666
TI  - Blindness as a challenging medical and social problem in China.
AB  - China, a country with about one fifth of the world's population, has been gaining
      a rapid economic growth since 1980s. This country has around 5 million blind
      people, accounting for 18% of the blind in the world. The major causes of
      blindness include cataract, corneal diseases, trachoma, glaucoma,
      vitreoretinopathy and a number of factors contributing to blindness in children.
      The principal cause of blindness in China was no longer trachoma but cataracts.
      Vitamin A deficiency remains a public health problem in the under-developed
      areas. Age-related conditions in China, such as vision loss due to cataract and
      retinal disorders, will increase accordingly if no preventive meaunes are taken.
      Glaucoma and diabetic retinopathy appear to be predominant induction of the
      devastating blind. In this fast developing country blindness is not only a
      medical or health, but also a social problem. Developed strategies have been
      adopted simultaneously by national efforts under the leadership of the
      government, international agencies, nongovernmental organizations, as well as
      private sectors in their every-day work to prevent and treat blindness.

PMID- 15510667
TI  - Indocyanine green angiographic and multifocal electroretinographic features in
      the diffuse and regional form of Bietti's crystalline retinopathy.
AB  - PURPOSE: To observe different features of indocyanine green angiography (ICGA)
      and multifocal electroretinography (ERG) in the diffuse and regional type of
      Bietti's crystalline retinopathy (BCR). METHODS: ICGA and the multifocal ERG were
      performed in two cases of the diffuse and regional type of BCR respectively.
      These data were compared with fluorescein angiography (FA), standard Ganzfeld
      ERG, and visual field testing. RESULTS: In the regional case, ICGA revealed
      reduced perfusion of the choroidal circulation in the early phase and multiple
      hypofluorescent spots in the posterior pole in the late phase, due to
      choriocapillaris filling defect; the extent of choroiocapillaris loss was shown
      in early phase of ICGA and there were multifocal hyperfluorescent dots
      surrounding hypofluorescent spots in late phase in the diffuse case. The
      multifocal ERG showed that the central responses were markedly depressed,
      corresponding to the visual field defects, while the findings of Ganzfeld ERG
      were normal in the regional BCR; however, both the multifocal ERG and Ganzfeld
      ERG were severely subnormal in the diffuse case. CONCLUSIONS: The features of
      ICGA and multifocal ERG are different between the diffuse and regional BCR. In
      the meantime, the two tools are also useful to differentiate the type and assess
      the extent of evolution in BCR.

PMID- 15510668
TI  - Optic coherence tomography of idiopathic macular epiretinal membranes.
AB  - OBJECTIVES: To study the characteristics of optical coherence tomography (OCT) in
      idiopathic macular epiretinal membranes (IMEM) and the relationship between the
      thickness of fovea and the vision of affected eyes. METHODS: A total of 67 cases
      (73 eyes) with clinical diagnosis of IMEM using direct, indirect ophthalmoscope,
      three mirror contact lens, fundus color photography or fundus fluorescein
      angiography (FFA) were examined with OCT. RESULTS: Epiretinal membranes (ERMs)
      with macular edema were found in 32 eyes, proliferative ERMs in 20 eyes, ERMs
      with macular pseudoholes in 14 eyes and ERMs with laminar macular holes in 7
      eyes. Based on OCT, the ERMs were clearly and partially seperated from the
      retinal (27 eyes, 38. 36%), the retinal thickness of the fovea was the thickest
      in the proliferative ERMs and the thinnest in the ERMs with laminar macular
      holes. The statistical analysis showed there was a negative correlation between
      the thickness of fovea and visual acuity (r = - 0. 454, P = 0. 000). CONCLUSION:
      There were four types of images of OCT in IMEM: ERMs with macular edema,
      proliferative ERMs, ERMs with macular pseudohole and ERMs with laminar macular
      hole; and the thicker the fovea under the OCT, the poorer the vision acuity in
      the affected eyes with ERMs.

PMID- 15510669
TI  - The abnormal choroidal vessels in aged patients.
AB  - BACKGROUND: To show the abnormal choroidal vessels in aged patients with
      indocyanine-green angiography (ICGA). METHODS: ICGA was performed in 350 patients
      with TOPCON TRC-50IA fundus camera. The images were recorded and retrospectively
      reviewed. RESULTS: Five aged patients out of 350 cases were found to have
      abnormal choroidal vessels. The incidence was 1.43%. The abnormal choroidal
      vessels showed round- shapet, focal enlargement, abnormal shape and entrance,
      satellite appearance, and vascular loops. These might be due to congenital
      abnormality of choroid. CONCLUSION: ICGA could be used to observe the abnormal
      choroidal vessels.

PMID- 15510670
TI  - Application of foldable intraocular lens in multiple types of cataract.
AB  - OBJECTIVE: To evaluate the clinical results of implantation of foldable
      intraocular lens in multiple types of cataract. METHODS: This retrospective study
      comprised 162 eyes of 148 patients undergoing phacoemulsification and
      implantation of foldable intraocular lens, some of whom underwent combined pars
      plana vitrectomy or trabeculectomy or silicone oil removal. The period of follow
      up was from 3 months to 17 months. RESULTS: There is slight reaction
      postoperatively in all cases. The postoperative uncorrected visual acuites was
      from 0.05 to 1.2, patient with 0.6 or above acuity were 70.98%. A neodymium: YAG
      capsulotomy was required in 5 eyes. Posterior capsule ruptured in 1 eyes, and a
      PMMA intraocular lens was implanted in ciliary sulcus. In one eye, a lens was
      removed because of recurrence of retina detachment. CONCLUSIONS: The application
      of foldable intraocular lens in multiple types of cataract is safe, and there is
      a slight postoperative reaction. less complications, and fast visual acuity
      recovery.

PMID- 15510671
TI  - Bilateral central retinal vein occlusions combined with artery occlusions in a
      patient with acquired immune deficiency syndrome.
AB  - PURPOSE: This is the first report of a bilateral nonischemic central retinal vein
      occlusions combined with artery occlusions in a patient with acquired immune
      deficiency syndrome (AIDS). METHODS: Case report. RESULTS: A 22-year-old Chinese
      (male) with a positive human immunodeficiency virus (HIV) infection developed
      bilateral nonischemic central retinal vein occlusions combined with artery
      occlusions and severe vision loss. The manifestations of the fundus and
      fluorescein angiography were similar in both eyes. CONCLUSION: This case report
      provides the evidences that central retinal vein and artery occlusions are
      probably part of the spectrum of AIDS vascular diseases.

PMID- 15510672
TI  - A preliminary report of 40 cases of strabismus microsurgery.
AB  - OBJECTIVE: To improve the quality of strabismus surgery and to find out the role
      of microsurgery in the field of strabismus. METHODS: We performed separation and
      preservation of anterior ciliary vessels (ACV), adjustable sutures, routine
      rectus recession, and oblique muscle surgeries under microscope in 13 cases of
      comitant strabismus, 19 cases of A-V syndrome and 8 cases of paralytic
      strabismus. RESULTS: Surgeries were performed in a very clear field under
      microscope. We successfully did vascular microdissection and ACV preservation.
      Also with the use of microscope, various kinds of strabismus microsurgery videos
      were recorded. CONCLUSIONS: Microscopic technique can be used to enhance the
      quality and accuracy of strabismus surgery and to reduce surgical damage,
      postoperative inflammatory reaction and scar formation. All kinds of strabismus
      surgery , especially, oblique muscles and complex paralytic operations can be
      performed under microscope.

PMID- 15510673
TI  - Aquaporin-1 expressed in cultured human trabecular meshwork cells.
AB  - OBJECTIVE: To determine if aquaporin-1 could be detected in cultures of human
      trabecular meshwork cells. METHODS: Using primers specific for aquaporin-1,
      reverse transcription combined with polymerase chain reaction (RT-PCR) yielded a
      product and its size with total RNA prepared from the human trabecular meshwork
      cells. SDS-PAGE and immunoblotting were also used in this study to detect the
      specific water channel. RESULTS: The presence of this product and its size (298
      base pairs) are consistent with that of an aquaporin-1 message in these cells. A
      band of 28 kD in agreement with the molecular size of aquaporin-1 was showed in a
      film by immunoblotting. CONCLUSION: The presence of aquaporin-1 in human
      trabecular meshwork cells, the predominant cell-type of the primary outflow
      region of the human eye, suggests that water channels may be involved in the
      movement of aqueous fluid out of the eye. In addition, the existence of aquaporin
      1 on cultures of human trabecular meshwork cells provides an in vitro model to
      study the endogenous expression of aquaporin-1 and its possible role in the
      regulation of aqueous outflow.

PMID- 15510674
TI  - Pluripotent embryonic stem cells developed into medulloepithelioma in nude mice
      eyes.
AB  - PURPOSE: The pluripotent embryonic stem cells can differentiate into various
      kinds of normal tissues. There is no previous report on the differentiation of
      embryonic stem cell in the intraocular environment. In this paper, the authors
      tried to investigate the intraocular growth character of mice embryonic stem
      cells in nude mice. METHODS: Murine embryonic stem cells were cultured and
      maintained in an undifferentiated state in vitro. They were transplanted into the
      right eyes of 20 nude mice by microinjection under operating microscope. Animal
      eye observation, light microscope and immunohistochemical examinations were
      implemented. RESULTS: Two to three days after transplantation, small pieces of
      gray-white material could be viewed in the vitreous cavity. Between the 15th and
      20th day, the gray-white mass grew into the anterior chamber in 4 nude mice eyes.
      Then, the mass at the anterior chamber extended extraocularly. On the 30th day, a
      remarkable proptosis was observed in two of the four nude mice. In 6 to 45 days,
      the mice were executed for morphological examination which showed the following
      typical structures: (1) Undifferentiated cells with prominent nucleolius. (2)
      Flexner-Wintersteiner-like rosettes. (3) Medulloepithelioma-like structure: the
      cells were arranged in sheets, cords, tubes, and cysts. (4) Large, spindle-or
      astrocyte-like cells. (5) Cartilage-like structure. Immunohistochemically, most
      of the cells were highly positive in NSE staining and a few cells were moderately
      positive in GFAP staining. CONCLUSIONS: Both animal eye findings and morphologic
      examinations certificated that the transplanted embryonic stem cells could grow
      in the eyes of nude mice and differentiate into intraocular medulloepithelioma.

PMID- 15510675
TI  - Effects of nerve growth factor on proliferation and DNA synthesis of cultured
      human fetal retinal pigment epithelium cells.
AB  - OBJECTIVE: To investigate the effects of nerve growth factor(NGF) on
      proliferation and DNA synthesis of cultured human fetal retinal pigment
      epithelium(RPE)cells in vitro. METHODS: Primary culture and subculture of human
      fetal retinal pigment epithelium cells were established in vitro first. Cultured
      RPE cells were treated with NGF by various concentrations 0 micro1g/L, 50
      microg/L, 100 microg/L, 200 microg/L and 300 microg/L(final concentration) for 48
      hs. After 48 hs, cells proliferation was measured with methyl thiazolyl
      tetrazolium (MTT) assay method and the amount of DNA was determined by the
      absorbance at 280 nm of nucleic acid & protein analysis. RESULTS: The A values of
      100 microg/L, 200 microg/L, 300 microg/L NGF was(0.2137 +/- 0.233), (0.2188 +/-
      0.0181), (0.2322 +/- 0.0164) as compared with(0.1897 +/- 0.0152) of A value of 0
      microg/L NGF respectively, q value was 3.63, 4.40, 6.42 and P value was 0.015,
      0.000, 0.000( q-test). The DNA concentrations of 100 microg/L, 200 microg/L, 300
      microg/L and 400 microg/L NGF was (981. 220 4 +/- 123. 535 7), (1 375. 848 4 +/-
      244. 471 8), (1 658. 707 1 176. 938 1), (2 353. 086 3 +/- 609. 906 4) microg/ml
      as compared with (666. 818 8 +/- 141. 330 2) microg/ml of DNA concentration of 0
      microg/L NGF respectively, q value was 3. 63,8. 20,11. 47,19. 46, P value was 0.
      024,0. 000,0. 000,0. 000(q-test). CONCLUSION: The data suggested that NGF could
      stimulate the proliferation and DNA synthesis of cultured of hRPE cells in vitro
      in a dose-dependent manner.

PMID- 15510676
TI  - Experimental study of effect of perfluorohexyloctane to retina.
AB  - OBJECTIVE: To investigate the effect of perfluorohexyloctane to the retina of
      rabbit eyes. METHODS: Perfluorohexyloctane (experimental group) or BSS(control
      group) into vitreous cavities of fifteen vitrectomized New Zealand white rabbits.
      A slit-lamp biomicroscope and an indirect ophthalmoscope were used to examine all
      the eyes pre- and postoperation. Histopathological examination was performed
      after the rabbits were sacrificed. RESULTS: Perfluorohexyloctane was injected
      into the vitreous cavity forming a single large layerclear globe. No retinal
      detachment and cataract were found. The edema of outer plexiform was significant,
      and then get a darker cytoplasm and nucleoplasm. CONCLUSIONS:
      Perfluorohexyloctane in vitreous cavity had significant side effects on retina.
      As a silicone solvent, it should be removed out completely after injection. We
      don't recommend to use it as a new intraocular tamponade.

PMID- 15510677
TI  - Effect of intracameral lidocaine anesthesia on the anterior segment of rabbit
      eyes.
AB  - PURPOSE: To evaluate the effect of intracameral anesthesia on the anterior
      segment of rabbit eyes using chinese-made lidocaine. METHOD: The study comprised
      eight eyes of four white rabbits which were divided into three groups according
      to the concentration of the lidocaine given. They are 0.5%, 1%, 2% lidocaine
      groups and balanced salt solution (BSS) control group. Each group contained two
      eyes. After 0.5 ml of the anesthetic agent was injected into the anterior chamber
      and retained there for ten minutes, the rabbits were executed and the eye balls
      were enucleated. Pathological examinations of the anterior segment, including
      cornea, iris and ciliary body, were carried out immediately. RESULT: The
      pathological study revealed no abnormal findings in lidocaine 0.5% and 1% groups
      compared with the control group, where as in the lidocaine 2% group, much
      abnormal pathological change was found, including the shrinkage of corneal
      endothelium, stroma edema of iris and ciliary body. CONCLUSION: Using
      intracameral anesthesia of high concentration of chinese-made lidocaine would run
      a risk of damaging the anterior segment of rabbit eye. But at the low
      concentration usually used in cataract surgery, no adverse effect was found.

PMID- 15510678
TI  - Effect of seawater soaking on explosive cornea injury.
AB  - OBJECTIVE: To observe the changes in corneal tissue after explosive corneal
      injury and the effect of seawater soaking on the healing of cornea after
      explosive injury with the help of optical microscope. METHODS: Make 10 similar
      explosive injury models of rabbit's eyeball using 10 adult grey rabbits. For each
      rabbit, both eyes are artificially injured through explosion; its right eye is
      the comparison eye and after the injury the left eye is soaked in seawater for 30
      minutes. (Conduct slit lamp examinations, fluorescein dyeing, and ultrasonic
      cornea thickness metering on the corneas at intervals, that is, before the
      injury, 1, 2, 3, 4, 5, 7, 9, 12, 15 days after the injury respectively. Examine
      the corneas under the optical microscope and make comparisons. RESULTS: The
      corneal thickness of the experiment eye becomes apparently thicker than that of
      the comparison eye after the injury. The corneal clouding of the former
      apparently aggravates compared with the latter. The healing of corneal epithelium
      in the injured eye is slower compared with that in the comparison eye.
      Comparative examination under the optical microscope shows: after the injury, the
      corneal tissue of the experiment eye changes distinctly, its healing is delayed
      and the vascularization degree becomes high in corneal stroma. CONCLUSION: Scars
      and vascularization of various degrees will appear in corneal stroma after
      explosive injuries. Seawater soaking will have bad effects on the healing of the
      cornea injured in explosions.

PMID- 15510679
TI  - Binomial distribution and estimation of the true prevalence of infected animals
      when pooled samples are used.

PMID- 15510680
TI  - Remarkable results from skin grafting for repair of sloughed hoof.

PMID- 15510681
TI  - The veterinarian and human public health.

PMID- 15510682
TI  - An ethicist's commentary on the case of a client who demands treatment by a
      specific veterinarian.

PMID- 15510683
TI  - Mycoplasma haemofelis and Mycoplasma haemominutum detection by polymerase chain
      reaction in cats from Saskatchewan and Alberta.
AB  - Hemobartonellosis is caused by Mycoplasma haemofelis, previously known as
      Haemobartonella felis. Cats infected with this organism typically develop
      regenerative anemia. The related species Mycoplasma haemominutum may also cause
      anemia. The purposes of this study were to use polymerase chain reaction
      technology to determine if both organisms exist in naturally infected cats from
      Saskatchewan and Alberta, and to determine if disease manifestation corresponds
      to mycoplasma species. Thirteen of 18 cats with regenerative anemia were
      infected, 12 with M. haemofelis and 1 with M. haemominutum. Eight of 22 cats with
      nonregenerative anemia were infected, 4 with M. haemofelis and 4 with M.
      haemominutum. Two of 20 cats with normal complete blood (cell) counts were
      infected with M. haemominutum. Although both mycoplasma species were identified,
      ill cats were more often infected with M. haemofelis.

PMID- 15510685
TI  - Recovery of putative taeniid eggs from silt in water associated with an outbreak
      of bovine cysticercosis.
AB  - Degenerate taeniid-like eggs consistent with Taenia saginata were recovered from
      sediment in the water supply of a beef feedlot under quarantine for Cysticercus
      bovis. Nine degenerate eggs in total were recovered from 482 modified flotation
      assays. Flotation controls of sediment spiked with known numbers of T. saginata
      eggs had poor egg recoveries, supporting the need for more sensitive assays for
      environmental samples.

PMID- 15510684
TI  - The variability of serological and molecular diagnosis of feline immunodeficiency
      virus infection.
AB  - Diagnosis of feline immunodeficiency virus (FIV) infection by polymerase chain
      reaction (PCR) has recently become available, but little is known about the
      performance of this assay. The purpose of this study was to determine the
      sensitivity and specificity of PCR diagnosis of FIV infection. Replicate aliquots
      of blood samples from cats identified as FIV positive or negative by 2 previous
      enzyme-linked immunosorbent assay (ELISA) results, and from clinically healthy
      dogs, were submitted to different laboratories for FIV serologic diagnosis and
      PCR. The PCR products obtained in 1 laboratory were sequenced to determine the
      FIV subtype. The PCR assays correctly identified 100%, 80%, and 50% of the FIV
      positive samples, and 100%, 90%, and 70% of FIV-negative samples. Each dog sample
      was reported as FIV PCR positive at least once, and FIV subtypes A, B, and C were
      identified. It was concluded that PCR tests currently available for FIV infection
      are unreliable, with highly variable sensitivity and specificity.

PMID- 15510686
TI  - Traumatic mitral valve avulsion from the annulus fibrosis producing acute left
      heart failure in a dog.
AB  - Traumatic detachment of the mitral valve from the annulus fibrosis occurred in a
      dog following blunt chest trauma. Euthanasia was elected approximately 7 months
      posttrauma due to refractory, chronic left heart failure. This is the first
      reported case of traumatic mitral valve rupture in a dog.

PMID- 15510687
TI  - Diagnosis of chronic active hepatitis in a miniature schnauzer.
AB  - A 12-year-old male castrated miniature schnauzer was presented with a history of
      abdominal distension. Serum biochemical analysis and abdominal ultrasonography
      indicated hepatic disease. A wedge biopsy provided a diagnosis of chronic active
      hepatitis. A therapeutic regime was initiated to improve the quality of life and
      slow the progression of this disease is described.

PMID- 15510688
TI  - [Generalized thymic lymphoma in a 9-month-old ARK/J mouse].
AB  - Necropsy on a 9-month-old ARK/J mouse, presenting with a large thymic mass as
      well as generalized hypertrophic lymphadenopathy, revealed a generalized thymic
      lymphoma on histopathological examination. This strain of mouse is genetically
      predisposed to developing this type of neoplasm.

PMID- 15510689
TI  - Malignant adrenal neuroblastoma in a young dog.
AB  - A 1.5-year-old dog was evaluated for abnormal mentation, collapse, and weight
      loss. Radiographs and ultrasonographs revealed soft tissue masses in the mid
      abdomen. Ultrasound-guided fine-needle aspirates provided a diagnosis of
      malignant epithelial or round cell neoplasia. Histopathologic and
      immunohistochemical findings on the tumors were consistent with a primitive
      neuroblastoma.

PMID- 15510690
TI  - Alkali burns to the right eye.

PMID- 15510691
TI  - Acute bilateral suppurative otitis media in a dairy cow.

PMID- 15510692
TI  - Showing leadership in welfare: position statements and some of their
      consequences.

PMID- 15510693
TI  - A question of survival.

PMID- 15510694
TI  - Improving data quality in community-based seafood consumption studies by use of
      two measurement tools.
AB  - A seafood consumption study w as conducted in Glynn County, Georgia, to address
      concern about bioaccumulation of mercury from a nearby hazardous waste site in
      people who ate potentially contaminated seafood from this area. Seafood
      consumption levels were ascertained with two data collection tools: a
      questionnaire and a dietary diary. The use of two instruments allowed for more
      detailed analysis to reveal discrepancies in responses between the two
      instruments, to improve reliability of study results, and to reduce recall bias.
      Implementation of the questionnaire was relatively easy and provided a broad
      characterization of consumption patterns in the area. The dietary diary was more
      time-consuming, resulting in a reduction in participation rates. It provided,
      however, more detailed information with which to address community concerns about
      adverse health effects from mercury exposure. Overall, individuals who
      participated in this study were able to make broad generalizations about the
      amount of seafood in their diet but were less accurate in estimating specific
      seafood consumption levels. In addition, the level of concordance between the
      questionnaire and the dietary diary was low with respect to seafood consumption
      levels. For investigators examining consumption patterns in a community, the
      decision to use a questionnaire, a dietary diary, or both will be influenced by
      the objectives of the study, the level of community concern, the number of study
      staff, and available resources.

PMID- 15510695
TI  - Critical thinking among environmental health undergraduates and implications for
      the profession.
AB  - During a study conducted in 2000-2002, the critical-thinking dispositions of
      undergraduate environmental health students at Illinois State University were
      found to have significant shortcomings. The critical-thinking-disposition scores
      were comparable to those of other undergraduates throughout the United States and
      Canada; nevertheless, these findings have significant implications for
      environmental health academic programs and the profession. Environmental health
      professionals commonly confront "ill-structured" problems, for which critical
      thiking is an essential skill. In addition, the challenges faced by the
      profession in terms of recognition, funding, and public support require a high
      level of critical thinking. This paper provides a number of recommendations for
      academic programs and professionals.

PMID- 15510696
TI  - The association of daily diabetes mortality and outdoor air pollution in
      Shanghai, China.
AB  - The objective of the study reported here was to assess the association between
      air pollution and daily diabetes mortality in Shanghai. Death records were
      collected for all individuals who lived in the Zhabei district of Shanghai and
      died from diabetes from January 1, 2001, to December 31, 2002. The authors used a
      time-series approach to study the acute effects of air pollution on diabetes
      mortality after controlling for long-term trends, weather variables, and day of
      the week. Each increase of 10 microg/m3 in PM10, SO2, or NO2 was found to
      correspond, respectively, to a 1.006 (95 percent CI: 1.000-1.012), 1.011 (95
      percent CI: 0.990-1.032), or 1.013 (95 percent CI: 1.000-1.026) relative risk of
      diabetes mortality in Shanghai. The air pollutants also were observed to have a
      greater effect on diabetics than on nondiabetics. These findings provide new
      evidence for the association between air pollution and diabetes mortality risk,
      and suggest that diabetics are more susceptible to air pollution than are
      nondiabetics.

PMID- 15510697
TI  - GIS--a proven tool for public health analysis.

PMID- 15510698
TI  - Economist finds more pluses than minuses in restaurant letter grades.

PMID- 15510699
TI  - Air pollution is a serious cardiovascular risk.

PMID- 15510700
TI  - DHS launches national center focusing on data visualization.

PMID- 15510701
TI  - When science crosses politics, I: The case of naturally occurring asbestos.

PMID- 15510702
TI  - When science crosses politics, I: The case of naturally occurring asbestos.

PMID- 15510703
TI  - Asbestos-related issues in Bellevue County.

PMID- 15510704
TI  - When science crosses politics II: Getting down to earth in the great wastewater
      disputes.

PMID- 15510705
TI  - Leadership--what is it and are you headed for it?

PMID- 15510706
TI  - On the matter of fluorescence bronchoscopy.

PMID- 15510707
TI  - Inspiratory muscle workload due to dynamic intrinsic PEEP in stable COPD
      patients: effects of two different settings of non-invasive pressure-support
      ventilation.
AB  - BACKGROUND: In severe stable hypercapnic COPD patients the amount of pressure
      time product (PTP) spent to counterbalance their dynamic intrinsic positive end
      expiratory pressure (PEEPi,dyn) is high: no data are available on the best
      setting of non invasive pressure support ventilation (NPSV) to reduce the
      inspiratory muscle workload due to PEEPi,dyn. METHODS: The objectives of this
      randomised controlled physiological study were: 1. To measure the inspiratory
      muscle workload due to PEEPi,dyn 2. To measure the effects on this parameter of
      two settings of NPSV in stable COPD patients with chronic hypercapnia admitted in
      a Pulmonary Division of two Rehabilitation Centers. Twenty-three stable COPD
      patients with chronic hypercapnia on domiciliary nocturnal NPSV for 30 +/- 20
      months were submitted to an evaluation of breathing pattern, PEEPi,dyn,
      inspiratory muscle workload and its partitioning during both assisted and
      unassisted ventilation. Two settings of NPSV were randomly applied for 30 minutes
      each: i- "at patient's comfort" (C): Inspiratory pressure support (IPS) was the
      maximal tolerated pressure able to reduce awake PaCO2 with the addition of a pre
      set level of external PEEP (PEEPe); ii- "physiological setting" (PH): the level
      of IPS able to achieve a > 40% and < 90% decrease in transdiaphragmatic pressure
      in comparison to spontaneous breathing (SB). A PEEPe level able to reduce
      PEEPi,dyn by at least 50% was added. RESULTS: During SB the tidal diaphragmatic
      pressure-time product (PTPdi/b) was 17.62 +/- 7.22 cmH2O*sec, the component due
      to PEEPi,dyn (PTPdiPEEPi,dyn) being 38 +/- 17% (range: 16-65%). Compared to
      SB,PTPdiPEEPi,dyn was reduced significantly with both settings, the reduction
      being greater with PH compared to C. CONCLUSIONS: In conclusion in severe COPD
      patients with chronic hypercapnia the inspiratory muscle workload due to PEEPidyn
      is high and is reduced by NPSV at a greater extent when ventilator setting is
      tailored to patient's mechanics.

PMID- 15510708
TI  - Inhalations of 5-ALA in photodynamic diagnosis of bronchial cancer.
AB  - BACKGROUND: Photodynamic bronchoscopy (PDD) allows for early detection of
      bronchial cancer. Adverse effects and high costs, partly related to general
      application of photosensitisers, are important limitations of the method. The
      local application of a photosensitiser could help to minimize these problems. In
      this study the validity and safety of inhaled 5-ALA have been tested. METHODS: We
      examined 49 patients (age 59 +/- 11, cigarette consumption 36 +/- 17 pack-years)
      with present or past respiratory neoplasms and other with increased risk of
      bronchial cancer by photodynamic bronchoscopy (Storz-D-light) after inhaled 5
      ALA. Biopsies were taken from the fluorescence-positive and negative foci
      (control). Symptoms and pre-/post-inhalation spirometry were analysed. RESULTS:
      The overall sensitivity was 82%, specificity 62%, positive predicted value (PPV)
      45% and negative predictive value (NPV) 90%. Specificity decreased to 53% and PPV
      to 15% when visible tumours were excluded. PDD, when added to white light
      bronchoscopy increased sensitivity by 2.1% and NPV by 6%, but decreased
      specificity by 35.4% and PPV by 53.1%. In a group of actual or past tumours the
      sensitivity increased by 22% and NPV by 34%, whereas specificity decreased by 26%
      and PPV by 35%. In 2 cases a drop in FEV1 above 10% of pre-inhalation value was
      observed but no clinically relevant symptoms were reported. CONCLUSIONS:
      Photodynamic bronchoscopy with inhalation of 5-ALA is a relatively safe
      diagnostic method. The main disadvantage is high percentage of false positive
      results. Nevertheless, we believe, that it may be a useful adjunct to
      conventional diagnostic modes, especially in the detection of early lesions in
      patients operated due to cancer (stump control and detection of metachronous
      lesions) and those prepared for operation (synchronous lesions and detection of
      infiltration margins). However all suspected lesions must be verified by histo
      pathological examination.

PMID- 15510709
TI  - Non-invasive positive pressure ventilation in acute hypercapnic respiratory
      failure: clinical experience of a respiratory ward.
AB  - BACKGROUND: Although a controlled trial demonstrated that non-invasive positive
      pressure ventilation (NIV) can be successfully applied to a respiratory ward (RW)
      for selected cases of acute hypercapnic respiratory failure (AHRF), clinical
      practice data about NIV use in this setting are limited. The aim of this
      observational study is to assess the feasibility and efficacy of NIV applied to
      AHRF in a RW in everyday practice. METHODS: Twenty-two percent (216/984) of
      patients consecutively admitted for AHRF to our RW in Arezzo (years: 1996-2003)
      received NIV in addition to standard therapy, according to pre-defined routinely
      used criteria. Tolerance, effects upon arterial blood gases (ABG), success rate
      (avoidance a priori criteria for intubation) and predictors of failure of NIV
      were analysed. RESULTS: Nine patients (4.2%) were found to be intolerant to NIV,
      while the remaining 207 (M: 157, F: 50; mean (SD) age: 73.2 (8.9) yrs; COPD:
      71.5%) were ventilated for >1 hour. ABG significantly improved after two hours of
      NIV (pH: 7.32 (0.06) versus median (Interquartiles) 7.28 (7.24-7.31), p<0.0001;
      PaCO2: 71.9 (13.5) mmHg versus 80.0 (15.2) mmHg, p<0.0001; PaO2/FiO2: 212 (66)
      versus 184 (150-221), p<0.0001). NIV succeeded in avoiding intubation in 169/207
      patients (81.6%) with hospital mortality of 15.5%. NIV failure was independently
      predicted by Activity of Daily Living score, pneumonia as cause of AHRF and Acute
      Physiology and Chronic Health Evaluation III score. CONCLUSIONS: In clinical
      practice NIV is feasible, effective in improving ABG and useful in avoiding
      intubation in most AHRF episodes that do not respond to the standard therapy
      managed in an RW adequately trained in NIV.

PMID- 15510710
TI  - Genetics of susceptibility to tuberculosis in humans.
AB  - There is substantial epidemiological evidence that host genetic factors in part
      determine susceptibility to mycobacteria, and many approaches have been applied
      to identify the specific genes involved. These include the study of single genes
      in 'knockout' mouse models and rare human families in which increased
      susceptibility to mycobacterial infection segregates as a single gene defect.
      Several genes have now been studied in many different populations. This review
      gives an overview of the progress made in the field of genetic susceptibility to
      tuberculosis and highlights more generally some of the challenges involved in the
      identification of complex disease genes.

PMID- 15510711
TI  - Water and sodium imbalance in COPD patients.
AB  - Water retention and hyponatraemia are typically observed in the final stages of
      Chronic Obstructive Pulmonary Disease (COPD) and the onset of edema is a poor
      prognostic factor. For several years the pathogenesis of edema in COPD patients
      was attributed to heart impairment because of pulmonary hypertension, but the
      evidence that cardiac output is often adequate for the metabolic demands has
      suggested, since 1960, that the pathogenesis of edema in these patients would be
      correlated with gas exchange impairment and in particular with carbon dioxide
      (CO2) retention. The gas exchange impairment induces, in these patients several
      hormonal abnormalities: renin (Rn), angiotensin II (AnII), aldosterone (Ald),
      atrial natriuretic peptide (ANP), vasopressin (ADH) and endothelial factors are
      some of the factors involved. The systemic response to hypercapnia has the effect
      of reducing the renal blood flow and, as a result, increasing water and sodium
      retention with the final effect of edema and hyponatraemia. The aim of this brief
      review is to highlight the current knowledge on renal/hormonal abnormalities in
      COPD and their therapeutic implications.

PMID- 15510712
TI  - Endoscopic removal of a right main bronchus glomus tumor.
AB  - Glomus tumours in the respiratory tract are very rare. The majority of the
      reported cases have been surgically treated. An approach with rigid bronchoscopy
      to endobronchial lesions suspected to be carcinoid or other well vascularized
      tumours, as glomus tumor is, should be considered because it can allow a safe
      diagnosis and eventually be therapeutic avoiding more invasive and surgical
      procedures.

PMID- 15510713
TI  - Simultaneous pulmonary and intrathoracic lymph nodal granulomatosis of unknown
      significance (GLUS).
AB  - A case of a 30-year-old male with a fever, dry cough and associated abnormal
      findings in imaging modalities (bilateral hilar lymphadenopathy and nodular
      parenchymal opacities) is described. After a further and scrutinized work-up, the
      diagnosis of GLUS syndrome was made. Clinical, etiological, pathological and
      therapeutical aspects of the disease are discussed, demonstrating the paramount
      importance of the use of the immunohistochemical methods in the diagnosis of this
      disorder.

PMID- 15510714
TI  - Fibrosing mediastinitis causing rapidly progressive dyspnea, pulmonary edema and
      death in a 16 yr old male.
AB  - Idiopathic fibrosing mediastinitis is a rare entity involving more severely the
      more compliant structures within the mediastinum. In this report a rare case of
      simultaneous involvement of both the superior vena cava (SVC) and pulmonary veins
      is described in a 16--year old male with progressive dyspnea on exertion, cough
      and a three months' history of blood--tinged sputum. Physical examination and
      imaging studies revealed signs of pulmonary venous hypertension (PVH) and SVC
      stenosis. Fibrosing mediastinitis was confirmed by multiple biopsy samples.

PMID- 15510716
TI  - An unusual presentation of tuberculosis.
AB  - We describe a case of a male with no symptoms and normal chest X ray, diagnosed
      with TB. The chest computed tomography revealed a cavity formation on the upper
      left lobe.

PMID- 15510715
TI  - Difficult diagnosis of infliximab-related miliary tuberculosis.
AB  - The use of Infliximab in the treatment of patients with rheumatoid diseases
      unresponsive to conventional therapies has been reported to be complicated by
      opportunistic infections. We report the case of a 56-yr old female rheumatoid
      arthritis patient complaining of fever and respiratory symptoms 9 months after
      commencing Infliximab, who received no ethiologic diagnosis for the six months
      before admission. Tuberculosis was suspected upon chest radiographic pictures and
      empirical treatment for miliary tuberculosis instated in the wake of
      microbiological confirmation. The case typifies the difficulties of diagnosing
      miliary tuberculosis in the immunocompromised as well as in the immunocompetent
      patient.

PMID- 15510717
TI  - Pulmonary tuberculosis with multifocal skeletal involvement.
AB  - Skeletal tuberculosis accounts for 1-5% of all tuberculosis infections. Of these
      infections, 50% involve the vertebral column and only 0-5% involve ribs. Rib
      tuberculosis is seen in only 0.1% of all tuberculosis infections. Skeletal
      tuberculosis is localised to a single site in 90-95% of reported cases.
      Multifocal involvement is uncommon and is usually associated with disseminated
      disease. We present a case of pulmonary tuberculosis associated with multifocal
      skeletal involvement.

PMID- 15510718
TI  - Vitrectomy for epiretinal membranes: visual outcome and prognostic criteria.
AB  - The treatment of choice for epiretinal membranes (ERM) causing marked retinal
      distortion and substantial visual impairment remains vitreoretinal surgery. The
      purpose of this study was to evaluate the results of surgery performed in our
      department and to investigate the prognostic value of different factors such as
      preoperative best-corrected visual acuity (BCVA), pre-existing cystoid macular
      edema (CME), intra-operative peeling of the internal limiting membrane (ILM), age
      and duration of symptoms. Eighty-eight consecutive eyes of 88 patients were
      operated on for ERM from July 1998 to June 2000. Both idiopathic and secondary
      cases were included. In all cases the ERM was successfully removed from the
      fovea. Mean BCVA after surgery increased from Snellen 0.2 (hand motion (HM) -
      0.6) to Snellen 0.5 (HM - 1.0) (p<0.0001). Our results confirm the efficacy of
      surgical removal of the ERM in improving the visual acuity. Although not
      statistically significant, mean postoperative BCVA was slightly better in the
      group without pre-existing CME (p>0.05) and in the group where peeling of the ILM
      was performed (p>0.05). The data suggest that early surgery is likely to decrease
      the risk of developing irreversible macular damage (p<0.05). Because accelerated
      nuclear sclerosis with visual impairment is a common phenomenon after vitrectomy,
      one might consider performing a phaco-emulsification at the same time, especially
      in the elderly.

PMID- 15510719
TI  - Macular CMV retinitis: a case report.
AB  - PURPOSE: Cytomegalovirus (CMV) retinitis is the most common ocular opportunistic
      infection associated with AIDS. It usually affects the peripheral retina, sparing
      the macula. We describe an atypical CMV retinitis exclusively confined to the
      macula. METHODS: A 43-year-old man with the diagnosis of AIDS developed a white
      retinal lesion confined to the macula of the right eye. Two weeks later, a more
      typical granular appearance was observed leading to presumption of CMV retinitis.
      RESULTS: The patient was treated with ganciclovir without success. With
      foscarnet, a good response was obtained, leading to total healing of the lesion.
      CONCLUSIONS: CMV retinitis has to be taken into consideration in all lesions
      confined to the macula in immunodepressed patients. An early diagnosis is crucial
      to avoid blindness.

PMID- 15510720
TI  - Long term follow-up of birdshot chorioretinopathy.
AB  - BACKGROUND: To report the long term follow-up of a case of Birdshot
      Chorioretinopathy treated with steroids and cyclosporine during three years and
      followed for twenty years. METHODS: The patient was monitored with Snellen visual
      acuity, slit lamp examination, perimetry, colour vision test, fluorescein
      angiography, electroretinogram (ERG) and electrooculogram (EOG). RESULTS: The
      retinal alterations progressed despite minimization of the intraocular
      inflammation. Vision dropped, perimetric and severe colour vision alterations
      appeared and the patient complained of nyctalopia. CONCLUSIONS: The retinal
      findings in our case treated during three years resemble twenty years later
      tapetoretinal dystrophy and evoke the natural evolution of Birdshot
      Chorioretinopathy. The therapeutic approach was either inadequate due to early
      interruption or to inefficacy on the mechanisms of the retinal alterations.

PMID- 15510721
TI  - [Use of corneal pachymetry in ocular hypertension and chronic glaucoma].
AB  - Among the numerous corneal variables that may influence the determination of the
      "true" intraocular pressure (IOP) from applanation tonometry measurements and
      considering the still non conclusive scientific data on all the different aspects
      of this topic, the measurement of the central corneal thickness (CCT) may be an
      interesting diagnosis tool in hypertensive and glaucomatous patients. As far as
      the physiologic variability of the corneal thickness is considered, the
      measurement of CCT can potentially become an important confounding variable when
      measuring applanation tonometry in patients with ocular hypertension. It could
      also improve the management of patients with normal tension glaucoma and patients
      with suspicious optic discs. In these three groups, the measurement of CCT may be
      useful in determining if there is an artefactual error in the IOP measurement due
      to a thicker (too high) cornea or thinner (too low) cornea. Therefore the IOP
      corrected by CCT may change or influence a decision to initiate or modify
      treatment. CCT measurement has also proved to be crucial in patients who have
      undergone laser refractive surgery.

PMID- 15510722
TI  - Chronic granulomatous disease and peripheral ulcerative keratitis: a rare case of
      recurrent external ocular disease.
AB  - CLINICAL REPORT: We report a case of a 29-year-old lady, with known Chronic
      Granulomatous Disease, who presented with an acneiform scarring facial and trunk
      eruption and sore red eyes. Slitlamp examination showed limbal granulomas and
      adjacent peripheral ulcerative keratitis. DISCUSSION: The authors are considering
      the possible causes of the keratitis. As there were no signs of blepharitis at
      the time of initial presentation, the keratitis was most likely mediated by the
      adjacent limbal granuloma, and not due to Staphylococcal hypersensitivity.
      CONCLUSION: Although ocular involvement in CGD has been described before, this is
      the first article that describes limbal granulomata and peripheral ulcerative
      keratitis. Multidisciplinary management with longstanding oral antibiotic
      treatment, and topical combined antibiotic-steroid treatment were required to
      bring the condition under control.

PMID- 15510723
TI  - Presumed optic nerve sheath meningioma diagnosed after complicated retrobulbar
      anesthesia.
AB  - We present a patient who developed acute visual loss and light flashes at
      retrobulbar anesthesia for cataract extraction. Vision improved only slightly
      after cataract surgery. Although traumatic optic neuropathy was suspected, the
      patient was diagnosed one year later with an optic nerve sheath meningioma
      (ONSM). ONSM is a rare, slow growing, benign tumour with highly variable clinical
      features. Diagnosis is often delayed. This case report demonstrates the
      diagnostic difficulty of this tumour.

PMID- 15510724
TI  - Intraocular lens exchange for late-onset opacification.
AB  - PURPOSE: To report on the clinical, light microscopic and spectroscopic analyses
      of Hydroview intraocular lenses (IOLs) explanted for late postoperative IOL
      opacification. MATERIAL AND METHODS: Retrospective study of all cases with
      secondary lens implantation performed at the University Hospital of Antwerp
      during a period of one year (2002-2003) for postoperative opacification of
      Hydroview IOLs. Further analyses on some of the explanted IOLs included gross and
      light microscopic evaluation and RAMAN spectroscopy. RESULTS: Lens exchange for
      late-onset IOL opacification was needed in seven eyes of six patients. IOL
      opacification became apparent between 15 and 25 months after uneventful
      phacoemulsification and lens implantation. Visual acuity varied from < 0.05 to
      0.6 before explantation. In almost all cases postoperative visual acuity improved
      to the pre-opacification level. Light microscopic and spectroscopic analyses
      showed that the opacification was mainly located in the anterior portion of the
      IOL optic as a layer of irregular granular deposits composed of calcium
      phosphate. CONCLUSION: Late postoperative opacification of Hydroview IOLs may
      cause severe visual impairment, requiring explantation. Calcium phosphate is
      involved in the formation of these opacifications. Reporting on this type of
      complications is mandatory according to the Belgian and European directives for
      medical devices.

PMID- 15510725
TI  - Lacrimal drainage obstruction by Ascaris lumbricoides.
AB  - Lacrimal drainage obstruction by Ascaris lumbricoides is extremely rare and only
      few cases have been documented. We report an additional case from the Democratic
      Republic of Congo.

PMID- 15510726
TI  - [An analysis of a large hereditary postlingually deaf families and detecting
      mutation of the deafness genes].
AB  - OBJECTIVE: To make a further exploration of the mutation frequence of Chinese
      genetic deafness and make clear if the genetic deafness genealogy that we
      collected recently was resulted from the mutation of the deafness genes which had
      been cloned. METHOD: We made regular otologic examination, hearing test and
      physical examination among the members of this genealogy, and also inspected the
      mutation of seven autosomal domiant deafness genes, HDIAI,GJB2, GJB3, DFNA5, a
      tectorin(resulting in two types of genetic deafness, DFNA8 and DFNA12),
      MYO7A,POU4F3, with PCR-Sequencing method in this genealogy. RESULT: 1. The
      analysis of hereditary mode: There were forty-seven persons collected in five
      generations of this genealogy, and eighteen persons of them were deafness. It
      accorded with autosomal dominant inheritance from the pedigree. 2. The clinic
      feature: All patients with deafness were postlingual deafness. Their hearing
      decreased onset between sixteen to thirty years old, and the deafness was
      binaural symmetrical, progressive sensorineural and without other systems
      abnormity. 3. Analysis of mutation detection: We found two nucleotides changes in
      CX26 genes, A341G and GC257-258CG, and one changed nucleotide in POU4F3
      gene,T90C. But we didn't think the changed nucleotides caused deafness after we
      analysed them. No mutation was found in other five genes. CONCLUSION: The
      possibility that the deafness of this genealogy was resulted from the cloned gene
      is relatively small. Now, We are scanning the whole gene groups and making
      linkage analysis on this pedigree, it is most probably to orientate a new
      deafness gene position.

PMID- 15510727
TI  - [Computerized tomographic evaluation of traumatic ossicles disruption].
AB  - OBJECTIVE: To investigate the importance of the high resolution computerized
      tomography of temporal bone in evaluation of traumatic lesions, particularly of
      the ossicular disruption. METHOD: Ten patients with traumatic ossicles
      dislocation underwent preoperative CT scanning followed by surgical exploration
      of the middle ear. RESULT: The radiographic finding was consistent with the
      operative demonstration for malleoincudal disarticulation (3 ears),
      incudostapedial dislocation (7 ears), and the fracture of temporal bone (8 ears).
      CONCLUSION: The incus was the most vulnerable ossicle in the trauma to the middle
      ear. CT scans can diagnose exactly the damage position in middle ear.

PMID- 15510728
TI  - [Preoperative cochlear implantation imaging].
AB  - OBJECTIVE: To investigate the value of CT and MRI as preoperative imaging
      technique for cochlear implant candidates. METHOD: Axial high-resolution temporal
      bone CT and T2-weighted FSE-MRI were performed in 26 patients with sensorineural
      hearing loss. Three-dimensional reconstruction of inner ear was compared between
      CT and MRI. RESULT: There were 1 case (2 ears) with Mondini malformation type I ,
      1 case (2 ears)with Mondini malformation type II , 1 case (2 ears) with inner
      fibrosis in 18 patients with congenital sensorineural hearing loss. There were 1
      case (2 ears) with chronic suppurative otitis meadia, 1 case (2 ears) with inner
      ossification in 5 patients with postlingually deafness. CONCLUSION: CT plays an
      indispensable role in evaluation of cochlear implantation. T2-weighted FSE-MRI is
      necessarily complementary to CT. MRI three-dimensional reconstruction of inner
      ear is better than CT.

PMID- 15510729
TI  - [Investigation on the frequency specificity of the auditory brainstem response to
      tone burst in three different conditions].
AB  - OBJECTIVE: This study investigated and compared the effects of tone burst in
      three different conditions (linear-gated tone burst, linear-gated tone burst in
      broadband noise masking and Blackman-gated tone burst) on the frequency
      specificity of ABR. METHOD: The latencies of ABR wave V were recorded
      respectively on sixteen normal-hearing adults using 1, 2 and 4 kHz tone bursts in
      three types of stimuli at different intensities. RESULT & CONCLUSION: 1. Three
      types of tone bursts may evoke similar frequency-specific ABR when stimulus
      intensity was lower than 70 dB nHL for 1 kHz and any intensity for 2, 4 kHz. At
      the high-intensity(> or = 70 dB nHL) for lower frequency (1 kHz), however, linear
      gated tone burst had poor frequency specificity due to the increased effects of
      spectral splatter. To improve the frequency specificity, linear-gated tone burst
      should be mixed with masking noise or using Blackman-gated tone burst directly.
      2. Both linear-gated tone burst in broadband noise masking and Blackman-gated
      tone burst of 1 kHz, 2 kHz and 4 kHz at any intensity can produce frequency
      specific ABR, but response amplitudes were smaller for the broadband noise
      masking condition than for the Blackman-gated one. Therefore the Blackman-gated
      tone burst is prefered.

PMID- 15510730
TI  - [Comparison of curative effect between decompression and incision of
      endolymphytic sac].
AB  - OBJECTIVE: We compared the curative effect between endolymphytic sac
      decompression and incision of endolymphytic sac to explore a simple, effective
      surgical way with less complication. METHOD: 23 endolymphatic sac decompression
      and 22 incision of endolymphatic sac were performed routinely under general
      anesthesia. RESULT: 41 of 45 patients were followed up more than 2 years after
      the surgical procedure, 21 of which received endolymphatic sac decompression,
      while others received incision of endolymphatic sac. According to Chinese Meniere
      disease's diagnosis and curative effect standard evaluation criteria tried out in
      1996, 13 got grade A(completely controlled), 4 got grade B (fundamentally
      controlled), 3 got grade C (partially controlled) while 1 got grade D (not
      controlled) among 21 patients who received endolymphatic sac decompression. The
      fully control rate is 61.9%. Among 20 patients who received incision of
      endolymphatic sac, 12 got grade A (completely controlled), 5 got grade B
      (fundamentally controlled), 2 got grade C (partially controlled) while 1 got
      grade D (not controlled). The fully control rate is 60%. CONCLUSION: There is no
      significant difference between endolymphatic sac decompression and incision of
      endolymphatic sac in curative effect,but endolymphatic sac decompression is more
      convenient,safe and has less complication compared with incision of endolymphatic
      sac. From this,we favor endolymphatic sac decompression in selection of surgical
      method.

PMID- 15510731
TI  - [Clinical investigation on anacusis associated with chronic suppurative otitis
      media].
AB  - OBJECTIVE: To investigate the risk factors and clinical features of anacusis or
      severe deafness associated with chronic suppurative otitis media (CSOM ). METHOD:
      A retrospective review of 62 ears consecutive cases of severe deafness (15 ears)
      and anacusis (47 ears) associated with CSOM were investigated . There were 5 ears
      severe deafness deteriorated to anacusis after procedures. This represented 6.42%
      of our total series of CSOM with or without cholesteatoma in adults and children
      (965 ears) in 1993-2000. The series with cholesteatoma or granuloma or
      tympanosclerosis were 46 (74.19%) ears 13 (20.97%) ears and 3 (4.84%) ears
      respectively. The symptoms and operative findings were analyzed. All patients
      underwent preoperative CT scans and preoperative audiometry. With respect to
      surgical technique, the canal-wall-down procedure was performed in(50/62) 80.6%,
      and classical modified mastoidectomy was performed in(12/62) 19.4%. RESULT: The
      results demonstrated that chronic otorrhea with bloody, ossicular chain
      destructive and erosion of the supraplate structure or disappear of footplate
      were helpful predicting indicators for anacusis or severe deafness. There was a
      high significant association (Chi-square Fisher exact test P < 0. 001) with these
      factors compared with CSOM without anacusis or severe deafness. Labyrinthine
      fistula was also correlated to anacusis or severe deafness (P < 0.05). There were
      no significant with the courses and facial paralysis and revision mastoidectomy.
      CONCLUSION: Anacusis or severe deafness intimately associated with chronic
      otorrhea with bloody, ossicular chain destructive, erosion of the supraplate
      structure or disappear of footplate and labyrinthine fistula. The surgical
      procedure should be performed earlier to eradicate the chronic or acute infection
      and to avoid anacusis or severe deafness.

PMID- 15510733
TI  - [The study of MRI examination of acoustic neuromas].
AB  - OBJECTIVE: To discuss the examination parameters of acoustic neuromas. METHOD:
      The MRI features of 20 lesions 20 patients with acoustic neuroma had been
      analyzed retrospectively. The examinations were performed by a 1.5 Tesla
      superconducting magnet system transaxial T1. T2-weighted imagines and coronal or
      sagittal T1. T2-weighted imagines were obtained in each cases. 20 patients were
      examined with Gd-DTPA. RESULT: 20 cases of acoustic neuroma were divided into
      three groups according to the tumor size: 1.1 approximately 2 cm (4 lesion) ;2. 2
      approximately 4 cm (14 lesion); 3. over 4 cm (2 lesion). T1 weighted imagines
      shovos the equal or low signal;T2 weighted imagines shows the high signal. Low
      and high mixture signal will be shown when being hemorrhage or necrosis.
      CONCLUSION: Combining thin slice and Gd-DTPA in MRI examination was the best
      method to find acoustic neuroma. MRI not only can find small intracanalicular
      tumors, but also has advantages in demonstrating the formation of cyst and
      hemorrhage, the compression of adjacent anatomical structures and the tumor
      vessels.

PMID- 15510732
TI  - [Otoendoscopic tympanic segment and ganglion geniculi of facial nerve
      decompression via the attic approach].
AB  - OBJECTIVE: To research the practicability of otoendoscopic tympanic segment and
      ganglion geniculi of facial nerve decompression via the attic approach and the
      advantage of the operative procedure. METHOD: 12 patients with traumatic
      peripheral facial paralysis following temporal bone fracture (n = 11) and radical
      mastoidectomy (n = 1) underwent otoendoscopic tympanic segment, pyramidal segment
      or ganglion geniculi of facial nerve decompression via the attic approach. The
      injured positions were estimated before operation by high resolution CT scan,
      Schirmer test, acoustic reflex, taste test and hearing examination. RESULT: The
      facial muscle function of 6 cases (50%) recovered totally at time of discharge by
      Hosuse-Brackmann Standard. After 2-10 months of following up, 4 cases (33.3%)
      recovered totally and 2 cases (16.7%) remained light to medium facial paralysis.
      After operation, the hearing level unchanged (n = 8), descended (n = 2) and
      improved (n = 2) with auditory ossicle dislocation before operation. CONCLUSION:
      Otoendoscopic assisted tympanic segment and ganglion geniculi of facial nerve
      decompression via the attic approach can reach the target convenient and
      minimally destroyed normal structure. It is a mini-invasive approach for facial
      nerve decompression.

PMID- 15510734
TI  - [Observation of aspiration of laryngectomees in TE shunt speech without
      prosthesis].
AB  - OBJECTIVE: To investigate the course of variation and influencing factors on
      aspiration in laryngectomees who underwent tracheoesophageal (TE) shunt speech
      without prosthesis. METHOD: Sixteen laryngeal cancer patients who were operated
      on for TE shunt voice rehabilitation without prosthesis after total laryngectomy.
      These laryngectomees experienced aspiration in different degrees after the
      operation. We designed a questionnaire to follow up alteration aspiration.
      RESULT: Of sixteen laryngectomees, the longest follow-up time was nine years and
      six months, the shortest time was one year and three months, no one got lost in
      the follow-up. In the follow-up period, three laryngectomees died, other thirteen
      still survived. There were three basic aspiration variational courese: Seven
      patients changed from no leakage to slight leakage. Four patients remained slight
      leakage. Five patients changed from obvious leakage to slight leakage. Aspiration
      affect TE shunt speech in four different ways: No leakage, good voice; slight
      leakage, still good voice. No leakage,hard voice. If speak, take more time and
      use great effort. However,in some patients, if the slight leakage gradually
      appeared, the voice seemed to be better. If the slight leakage remained in the
      same degree,the patient got good voice all the time. Obvious leakage, hard voice.
      When leakage gradually became slight, voice grew better. There were no
      laryngectomees had the following situations: obvious leakage all the time, bad
      voice all the time. It was considered that radiation therapy induced aspiration
      in six laryngectomees. Neck infection and pharyngeal leak were believed to cause
      aspiration in five laryngectomees. CONCLUSION: Any surgical procedures with good
      voice, but no postoperative aspiration is the best choice in voice rehabilitation
      in laryngectomees. However, if some laryngectomees only have slight liquid food
      aspiration without interference with their normal diet; at the same time, those
      laryngectomees have high speech level,we consider the operation is acceptable.
      Definitely, radiation therapy, neck infection and (or) pharyngeal leak have some
      influence on aspiration. The variational course of aspiration and phonation
      change affected by aspiration are complex problems which need further
      investigation.

PMID- 15510735
TI  - [Clinical observation of 173 cases of partial laryngectomy].
AB  - OBJECTIVE: To summarize and study the clinical effect of partial laryngectomy on
      laryngeal neoplasms. METHOD: 173 cases of partial laryngectomy were performed. 6
      kinds of operations were performed, 49 vertical laryngectomy, 39 supraglottic
      laryngectomy, 4 frontolateral laryngectomy, 47 extended partial laryngectomy (
      with reservation of epiglottis and posterior part of thyroid cartilage), 17
      pearson's surgery, 17 near-total laryngectomy with cricoglossal anastomosis.
      RESULT: 168 cases restored their phonation, 145 cases were decannulated in three
      months after operations. The survival rates of three and five year was 79.77% and
      69. 94%, the local relapsing rate was 18.50%. CONCLUSION: Successful partial
      laryngectomy based on strict indications and correct operation choices. While the
      laryngeal function was reconstructed, it is necessary to restore the phonation,
      sphincter and respiratory function.

PMID- 15510736
TI  - [The study of expression of proliferating cell nuclear antigen and its gene in
      hypopharyngeal carcinoma].
AB  - OBJECTIVE: To study the relationship of proliferating cell nuclear antigen (PCNA)
      and the biological and clinical characteristics of hypopharyngeal carcinoma and
      its value of clinical prognosis. METHOD: The SABC-immunohistochemical method and
      in situ hybridization were correspondingly used to detect the expression of PCNA
      and its gene in 48 cases of cancer tissue and 15 cases of nearby cancer tissue of
      primary hypopharyngeal carcinoma. The number of positive cells of PCNA in 63
      cases of tissue was represented by proliferating index (PI). RESULT: The
      expression of PCNA correlated with the clinical stage, histological grade and
      clinical recurrence of hypopharyngeal carcinoma and prognosis of the patients,
      but did not correlate significantly with tumor location and whether metastasis of
      cervical lymph nodes or not. CONCLUSION: The expression of PCNA protein may
      provide a reference in evaluating the malignancy level of hypopharyngeal
      carcinoma and prognosis of the patients.

PMID- 15510737
TI  - [The study of correlation between HPV and vocal cord polyp].
AB  - OBJECTIVE: To reveal the correlation between HPV and human vocal cord polyp
      (vcp). METHOD: Analyzed the morphological changes of 99 vocal cord polyps stained
      with HE by microscope and 11 specimen by transmission electron microscopy and
      scanning electron microscopy; Meanwhile, HPV-DNA were detected in 50 vcp by PCR,
      and then a comparison analysis with the pathological results of vcp was made.
      RESULT: Koilocytoid cells were observed in 55 of 99 vcp (55.6%); The presence of
      HPV-DNA were detected in 34 of 50 vcp (68%), HPV-DNA positive rate was 92.9% and
      36.4% respectively in 34 cases with koilocyte-like cells expression and 22 cases
      without koilcyte-like cells expression; there was significant different. The
      results of electron microscopy agreed with the results under light microscopy
      except koilocyte-like cell expression. CONCLUSION: There is obvious correlation
      between HPV and vcp, HPV may play certain role in the occurrence of vcp.

PMID- 15510739
TI  - Professor Chenghu Zhou (1896 - 1978).

PMID- 15510738
TI  - [Culture of marginal cells from guinea pig cochlear stria vascularis explants].
AB  - OBJECTIVE: To provide the prerequisite for further investigation of drugs
      ototoxicity and the probable mechanisms, explant culture technique of guinea pig
      cochlear strial marginal cells were established. METHOD: 26 healthy pigmented
      guinea pig were randomly divided into four groups according to the period of
      stria vascularis cultivated: 24 hours group (n = 8); 72 hours group (n = 8); more
      than 72 hours group (n = 8); control group (fresh stria vascularis fixed group, n
      = 2). Several explants of stria vascularis and spiral ligament obtained by
      mechanical dissociation were cultivated and kept at 37 degrees C with maximal
      humidity in 5% CO2/95% air. The following culture media were used: E-MEM with
      hepes buffer (20 mmol/L), fetal calf serum (10%). RESULT: The normal activity of
      stria vascularis explants cultivated for 24 hours may maintain. There were no
      significant change in the structure features of stria vascularis between 24-hour
      group and control group. There were significant difference in the structure
      features between 72-hour group and control group. The stria vascularis of 72-hour
      group cannot be observed normal stria vascularis structure, the stria vascularis
      structure was loose, the marginal cells reached the border of the explant and
      they proliferated outside the explant. The marginal cells cultivated from the
      stria vascularis explant may be cultivated in cell-culture dishes for 13 days.
      CONCLUSION: Our present results suggested that explant culture technique of
      cochlear strial marginal cells of guinea pigs has been successfully established.
      The stria vascularis cultivated for 24 hours which be maintained normal activity
      and structure features may be used for further investigation of drugs ototoxicity
      and the probable mechanisms.

PMID- 15510740
TI  - High-resolution imaging of living retina through optic adaptive retinal imaging
      system.
AB  - PURPOSE: To evaluate the possibility as well as the usage of adaptive optics in
      high-resolution retinal imaging. METHODS: From March to November 2001, the fundus
      of 25 adults were checked by using Optic Adaptive Retinal Imaging System (OAS).
      The age of the subjects varied from 18 - 48 years. All had normal visual acuity
      from 0.9 to 1.0. No abnormality was found in the ocular examination, and their
      medical as well as ocular history was unremarkable. RESULTS: High-resolution
      images of the retinal cells, photoreceptor and bipolar cell, were analysed. In
      these images, the cells are clearly resolved. The density of the photoreceptor at
      area 1.5 degree from the foveloa is around 40 000 - 50 000/mm2. At area 3 degree,
      it drops to less than 30 000/mm2. CONCLUSION: Optic Adaptive Retinal Imaging
      System (AOS) is able to get high-resolution image of retinal cells in living
      human eyes. It may be widely used in ophthalmology experimentally and clinically.

PMID- 15510741
TI  - Exploration of multifocal rod electroretinograms recording in human.
AB  - PURPOSE: To test the feasibility of recording rod multifocal electroretinograms
      (ERG) in humans and observe appropriate recording conditions. METHODS: Multifocal
      rod ERG were recorded using a stimulus array of 61 equalsized hexagons in two
      normal subjects after the dark adaptation. Flashes were blue (W47B). Blank frames
      between two successive flashes of hexagons varied from 0 to 14. Length of the m
      sequence, bandwidth, flash frequency, flash intensities and background
      intensities were changed to obtain appropriate recording conditions for the
      clinical use. RESULTS: Multifocal rod ERG were clearly recordable and well
      formed. They had an early implicit time, very small negative wave and a late
      implicit time, large positive wave. The positive wave was bimodal, whose timing
      and waveform were similar to the full-field rod ERG. The local response
      amplitudes can be suppressed with increase in flash frequency or background
      intensity, decrease in flash intensity or the size of stimulus elements.
      CONCLUSIONS: Multifocal rod ERG can be recorded in human and can provide
      topographical maps of retinal function that have clinical usage. 2(12)-1 m
      sequence length, 3F blank frames and 3 - 300 Hz bandwidth were suggested to
      appropriate recording conditions.

PMID- 15510742
TI  - The preliminary report of pathological changes of epiretinal membranes and
      internal limiting membrane removed during idiopathic macular hole surgery.
AB  - PURPOSE: To investigate the pathological changes of epiretinal membranes (ERM)
      and internal limiting membrane (ILM) removed during idiopathic macular hole
      surgery. METHODS: Ten consecutive patients with a unilateral idiopathic macular
      hole underwent pars plana vitrectomy (PPV) with the surgical removal of the ERMs
      overlying the hole and ILM surrounding the hole. The pathological features of the
      excised tissues were examined under the microscope. RESULTS: According to the
      morphological changes, four ERMs showed cellular elements which looked like glia
      cells, macrophages, plasma cells, lymphocytes and fibroblast cells. Two of the
      ILM appeared as transparent membranes without cellular elements. The other eight
      ILM showed cellular elements on the transparent membranes. CONCLUSION: Our study
      supports the hypothesis that the tangential traction of vitreous and
      proliferative cellular elements on the inner surface of ILM causes idiopathic
      macular holes. Removal of the posterior cortical vitreous, ILM and proliferative
      cellular tissue is a valid treatment for IMH.

PMID- 15510743
TI  - Analysis of mitochondrial gene mutations in Chinese pedigrees of Leber's
      hereditary optic neuropathy.
AB  - PURPOSE: To investigate the frequency of common pathogenic primary mitochondrial
      DNA mutations in Leber's hereditary optic neuropathy (LHON) families. METHODS:
      Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and
      DNA sequencing were used to detect mitochondrial DNA mutations. Sixty-six Chinese
      examiners from 15 families, including 22 visual affected and their 44 unaffected
      maternal relatives, underwent molecular genetic evaluation. Eleven normal
      individuals underwent evaluation as control. RESULTS: Of the 15 families with
      suspicion of LHON, 13 had nucleotide position (nt) G11778A mutations, 2 had nt
      T14484C mutations. All examiners had nt G11719A mutations. CONCLUSIONS: The
      mutations at nucleotides 11778 and 14484 are primary LHON mutations. Molecular
      genetic findings suggest that the silent mutation at nt G11719A may be a common
      genetic polymorphism in Chinese.

PMID- 15510744
TI  - Study on IL-1alpha, IL-1beta and sIL-1ra in sera of patients with Graves'
      ophthalmopathy.
AB  - PURPOSE: To evaluate the relationship between the serum levels of IL-1alpha, IL
      1beta, sIL-1ra and the activity and the severity of Graves' Ophthalmopathy (GO),
      as well as the therapeutic responses to high-dose IV methylprednisolone. METHODS:
      Using enzyme linked immunosorbent assay (ELISA) systems, we measured serum
      concentrations of IL-1alpha, IL-1beta and sIL-1ra in 18 normal controls, 20
      active GO, 20 inactive GO, 18 Graves' disease(GD) on patients without
      ophthalmopathy and 10 active GO patients after high-dose IV methylprednisolone
      therapy. RESULTS: The baseline median sIL-1ra concentrations had no significant
      differences among active GO, inactive GO, GD and control groups. There was no
      correlation between baseline sIL-1ra levels and the severity of GO, cigarette
      smoking, and the responses to glucocorticoids therapy. However, responders had
      higher sIL-1ra levels (626.97 +/- 305.06 pg/ml) after glucocorticoids therapy
      than nonresponders (323.33 +/- 93.09 pg/ml). The concentration of IL-1alpha, IL
      1beta (< 3.9 pg/ml) in all samples was within the standards of the assays.
      CONCLUSION: The serum level of sIL-1ra in GO patients during high-dose IV
      methylprednisolone treatment is related to the therapeutic effect. The
      circulating baseline sIL-1ra concentrations are neither influenced by GO, the
      activity of GO, the severity of GO, GD, cigarette smoking nor predictive of the
      response to glucocorticoid treatment.

PMID- 15510745
TI  - The management of secondary glaucoma in nanophthalmic patients.
AB  - PURPOSE: To investigate the clinical characteristcs, management of secondary
      glaucoma in nanophthalmos, and the prevention of its complications. METHODS:
      Retrospectively, 9 cases (17 eyes) with nanophthalmic glaucoma were studied.
      RESULTS: The axial length of the eyes ranged (14.36 - 19.33) mm; All of the cases
      combined with hyperopia ranged (+7.00 +/- 16.00) D. All 17 eyes had the
      manifestation like angle-closure glaucoma. The glaucoma was controlled in 9 of 17
      eyes at the early stage, which underwent laser iridotomy (4 of 9 eyes also
      underwent laser iridoplasty). 1 eye underwent ciliary photocoagulation because
      its visual acuity was lost and the patient complained of pain. The other 7 eyes
      underwent filtration surgery and 3 of them had permanent loss of vision caused by
      disastrous complications after the surgery. CONCLUSIONS: Management of secondary
      glaucoma in nanophthalmos is complicated. The laser iris surgery is safe and
      effective in glaucoma at the early stage. Vortex vein decompression,
      sclerotectomy or anterior sclerotomy may be performed to reduce disastrous
      complications.

PMID- 15510746
TI  - Studies on the effects of the immunosuppressant FK-506 on the high-risk corneal
      graft rejection.
AB  - PURPOSE: To evaluate the clinical efficacy of FK-506 on suppressing high-risk
      cornea transplantation rejection. METHODS: In a randomized controlled clinical
      trial, 56 eyes of 56 patients with high-risk keratoplasty (including total
      corneal transplantation TCT, total corneal transplantation with circular lamellar
      sclera CST, vascularization corneal transplantation and corneal
      retransplantation) were divided into the experimental group and the control group
      (each with 28 eyes). The experimental group was treated by FK-506 eyedrops (0.5
      mg/ml) and TobraDex eyedrops, compared with the control group that was treated by
      1% CsA eyedrops and TobraDex eyedrops. In the average 8.1-month follow-up period,
      the visual acuity, graft transparent duration and Rejection Index (RI) of grafts
      were observed. RESULTS: In the follow-up period, the graft rejection rate of the
      experimental and the control group was 63.6% and 95.2% respectively (chi2 = 4.72,
      P < 0.05) with significant difference. CONCLUSIONS: The local application of FK
      506 suppressed effectively the graft rejection of corneal transplantation of the
      patients at high risk.

PMID- 15510747
TI  - Clinical application of the sapphire unfolder lens injection system.
AB  - PURPOSE: To summarize the clinical experience of 300 cases using the Sapphire
      unfloder intraocular lens (IOL) injection system. METHODS: After the standard
      phacoemulsification, an AR40e IOL was implanted using the Sapphire Unfolder. The
      involved problems during and after the operation were observed and analyzed.
      RESULTS: The complications occurred during the operation including the crack at
      the haptic-optic junction in 2 cases, slight kink in the haptic in 5 cases, IOL
      clamp into the cartridge in 2 cases, posterior capsular rupture in 2 cases and
      endothelium damage in the central small area in 4 cases. All the patients
      recovered successfully with IOLs in good CONCLUSION: IOL implantation with the
      Sapphire Unfolder led to no serious complications and got the satisfactory
      results.

PMID- 15510748
TI  - Morphometry of axons in optic nerves of Siamese's twins.
AB  - PURPOSE: To observe the development of optic nerve, we examined four optic nerves
      from Siameses Twins by absolute counts of axons. METHODS: Mean axon diameter,
      mean axon density, totally axonal population and optic nerve area were noted for
      each optic nerve. The mean axon diameter and the mean axon density were compared
      between paraxial (inner sectors) and cortical(outer sectors) areas of the nerves.
      RESULTS: More myelinated axons were seen in the inner sectors as compared to the
      outer sectors (average 11 axons/1000 microm2 in inner sectors and 34 axons/1000
      microm2 in outer sectors (P = 0.036). The myelinated fibers were also smaller (63
      microns) in the outer sectors as compared to the inner sectors (72 microns) (P =
      0.001). The average cross sectors area for the four 40 week stage optical nerves
      of Siamese Twins was 3.32 x 103 as compared to 1 million axons for 32-week-old
      normals. CONCLUSION: Our finding of fewer axonal number and small myelinated
      fibers in the Siamese Twins suggests hypoplasia. Myelination was more abnormal in
      the paraxial optic nerve than that in the peripheral sectors, suggesting
      anomalous development of optic nerve peripherally and delayed developnent
      centrally. Axonal density is higher in inner sectors than that in outer sectors,
      suggesting delayed development of the outer nerve sector.

PMID- 15510749
TI  - Clinical study on ocular trauma in children.
AB  - PURPOSE: To investigate the clinical characteristics of ocular trauma in children
      and put forward the major treatment and prevention of ocular trauma in children.
      METHODS: To analyze the clinical data by 77 eyes in 77 cases of ocular trauma in
      children from April 1999 to February 2002. RESULTS: The male and female were in
      the ratio of 2.21:1. Right eye ocular traumas were more than left ones. Ocular
      penetrating trauma was 83.12% and blunt trauma 12.99%. 41 cases (53.25%) were
      injured by themselves while 33 cases by others. 90.91% patients came from the
      countryside. CONCLUSION: The rate of blindness of children with ocular trauma
      could be reduced by prompt treatment. The study indicated that ocular trauma
      preventive publicity should be faced in the countryside in order to improve the
      understanding of the severity of ocular trauma and treat it as a social problem.

PMID- 15510750
TI  - The influence of central corneal thickness and corneal curvature and axial length
      on the measurement of intraocular pressure.
AB  - PURPOSE: To examine the influence of central corneal thickness (CCT), corneal
      curvature (CC), and axial length (AL) on intraocular pressure (IOP). METHODS:
      Eighty-one clinically normal eyes were included in our study. The IOP, CCT, CC,
      AL were measured using a Goldmann applanation tonometer, optical pachymeter,
      keratometer and A-scan ultrasound biometer respectively in all subjects. RESULTS:
      A highly significant positive correlation was identified between IOP and CCT.
      Linear regression analysis suggests that an increase in CCT of 0.010 mm is
      associated with a 4.946 mmHg increment in IOP. No significant positive
      correlation was identified between IOP and CC. P values are 0.724 and 0.414
      respectively for vertical and horizontal readings. A paradoxically reversed
      correlation was present between IOP and axial length. CONCLUSION: Corneal
      thickness is a very important confounding factor in the measurement of
      intraocular pressure, which warrants further attention in our clinical practice.

PMID- 15510751
TI  - Pterygium in aged population in Doumen County, China.
AB  - PURPOSE: To estimate the prevalence of pterygium and its influence on visual
      acuity in aged population of Doumen County, southern China. METHODS: A population
      based survey was conducted in Doumen County, the rural area of southern China.
      Twenty-seven sample units were selected by random sampling. The prevalence and
      severity of pterygium and it-related low visual acuity were analyzed. RESULTS: Of
      the total 4 762 individuals aged 50 years or over, 4 214 were examined. The
      prevalence of pterygium was 33.01% in subjects aged 50 years or above. There was
      a significantly higher prevalence in female (35.70%) than in male (29.70%, P =
      0.025). The prevalence of pterygium in age groups of 50s, 60s, 70s and 80s years
      old is 33.98%, 36.40%, 30.73% and 25.40%, respectively. Most of the pterygia were
      located in the nasal side (93.31%) of cornea, and only 6.69% in the temporal
      side. 0.92% of the eyes had visual acuity less than 0.32, which were directly
      caused by pterygia. CONCLUSION: The current survey suggests that the pterygium is
      one of the most common diseases of external eye in the population aged 50 years
      and above. It is still leading to the impairment of visual acuity in the rural
      area.

PMID- 15510752
TI  - Cloning and sequence analysis of light variable region gene of anti-human
      retinoblastoma monoclonal antibody.
AB  - PURPOSE: To clone the variable region gene of light chain of monoclonal antibody
      against human retinoblastoma and to analyze the characterization of its
      nucleotide sequence as well as amino acid sequence. METHODS: Total RNA was
      extracted from 3C6 hybridoma cells secreting specific monoclonal antibody (McAb)
      against human retinoblastoma (RB), then transcripted reversely into cDNA with
      olig-dT primers. The variable region of the light chain (VL) gene fragments was
      amplified using polymerase chain reaction(PCR) and further cloned into pGEM -T
      Easy vector. Then, 3C6 VL cDNA was sequenced by Sanger's method. Homologous
      analysis was done by NCBI BLAST. RESULTS: The complete nucleotide sequence of 3C6
      VL cDNA consisted of 321 bp encoding 107 amino acid residues, containing four
      workframe regions (FRs) and three complementarity-determining regions(CDRs) as
      well as the typical structure of two cys residues. The sequence is most
      homological to a member of the Vk9 gene family, and its chain utilizes the Jkl
      gene segment. CONCLUSION: The light chain variable region gene of the McAb
      against human RB was amplified successfully, which belongs to the Vk9 gene family
      and utilizes Vk-Jkl gene rearrangement. This study lays a good basis for
      constructing a recombinant antibody and for making a new targeted therapeutic
      agents against retinoblastoma.

PMID- 15510753
TI  - Different sensitivities to apoptotic induction by camptothecin between normal and
      senescent lens epithelial cells.
AB  - PURPOSE: To investigate whether normal and senescent lens epithelial cells have
      different defense abilities to apoptotic induction factor in vitro. METHODS:
      Rabbit lens epithelial cells were cultured, passed. When reaching confluence,
      cells from the first and seventh passage were stained by x-gal staining to detect
      cell senescence. Cell apoptosis was detected by TUNEL(Roche). 10 micromol/L
      camptothecin was used to induce cell apoptosis from the lens epithelial cells of
      the first and seventh passage to distinguish different sensitivities to apoptotic
      induction factor between normal and senescent cells. RESULTS: The senescent cells
      (41.17% +/- 5.24%) were detected in the lens epithelial cell culture of the
      seventh passage, which are higher than those of the first passage (0.98% +/-
      0.39%). There was no apoptotic cell detected in the cell cultures undisturbed.
      Exposure of the first passage cells to camptothecin resulted in death of
      approximately 23.87% +/- 3.45% of the cells during a 36 hour exposure period. In
      contrast, significantly more lens epithelial cells died through the apoptosis
      (38.29% +/- 4.01%) from the seventh passage. CONCLUSION: Senescent cells
      increased with cell passage. Senescence lens epithelial cells do not undergo
      apoptosis if they were not disturbed. But the vulnerabilities to apoptotic
      induction between health and senescence cells were different.

PMID- 15510754
TI  - Lactate dehydrogenase isoenzyme of lens in fetus.
AB  - PURPOSE: The LDH isoenzyme patterns were evaluated in lens of fetus to study the
      metabolism in human lenses. METHODS: LDH isoenzyme electrophoresis was performed
      in 15 lenses of human fetus aged from 4 - 6 months. RESULTS: There are 5 bands of
      LDH in fetus lens. LDH4 lever is the highest, and LDH1 is the lowest, especially
      in the cortex of lens. LDH1 is higher in lens of 4 months of age than in that of
      5 and 6 months of age. CONCLUSIONS: LDH isoenzyme in lens of fetus shows mainly
      anaerobic metabolism in development, but there is also aerobic metabolism,
      especially in younger fetus.

PMID- 15510755
TI  - Training in paediatrics.

PMID- 15510756
TI  - Prevalence and predictors of underweight, stunting, and wasting among children
      aged 5 and under in western Kenya.
AB  - The health and nutritional status of children aged 5 and under was assessed in
      three villages in Siaya District of western Kenya. A cross-sectional survey was
      conducted among 121 adults and 175 children during July 2002. Primary caretakers
      were interviewed during home visits to assess agricultural and sanitation
      resources, child feeding practices, and the nutritional status of their children
      aged 5 years and under. Through anthropometry, the prevalence of underweight,
      stunting and wasting were determined: 30 per cent were underweight, 47 per cent
      were stunted, and 7 per cent were wasted. Predictors of undernutrition were
      analysed using logistic regression controlling for age, sex, and SES, and four
      major findings emerged. First, children in their second year of life were more
      likely to be underweight and stunted. Second, children who were introduced to
      foods early had an increased risk of being underweight. Third, up-to-date
      vaccinations were protective against stunting, while reports of having upper
      respiratory infections or other illness in the past month predicted underweight.
      Finally, living with non-biological parents significantly increased risk of
      stunting. Emphasis should be placed on current immunization, prolonging exclusive
      breastfeeding, and improving access to nutrient-rich foods among adopted children
      and their families via community-based nutrition interventions.

PMID- 15510757
TI  - Impact of a standardized management protocol on mortality of children with
      diarrhoea: an update of risk factors for childhood death.
AB  - In the developing world, diarrhoeal disease is a significant cause of childhood
      morbidity especially amongst severely malnourished children. As a direct result
      of improved acute-phase management of this group of patients, there has been a 47
      per cent reduction in the death rate among severely malnourished children
      hospitalized at the ICDDR,B in Bangladesh. The change in the risk factors for
      death among children aged under 5 years presenting with diarrhoea was reassessed.
      The charts of 366 children under 5 years of age who were hospitalized for
      diarrhoeal disease in the year 1998 were retrospectively analysed. One hundred
      and eighty-three of these patients died and 183 of those who survived acted as
      controls. Univariate analysis found 12 significant risk factors on admission that
      impacted outcome. Only two factors, female sex and positive blood culture,
      remained significant in the multivariate analysis with odds ratios (95 per cent
      CI) of 2.05 (1.1-4.0) and 4.6 (1.7-12.4), respectively. Prior to the change in
      the protocol involving the management of severely malnourished children, only
      severe malnutrition and non-breastfeeding were found to be significant predictors
      of mortality.

PMID- 15510758
TI  - Efficacy of daily vs. weekly supplementation of iron in schoolchildren with low
      iron status.
AB  - Iron deficiency anemia (IDA) is still a major nutritional and public health
      problem in developing countries. The prevalence among young children and pregnant
      women is particularly high. Daily oral supplementation with medicinal iron is
      considered an effective strategy for reducing the incidence of IDA but non
      compliance is a major problem with this strategy. We undertook this study to
      compare the results of once-weekly vs. daily oral iron supplementation in
      schoolchildren. Sixty children ranging between 5 and 10 years with iron
      deficiency anemia were selected from a school in Karachi, Pakistan and were
      divided into two equal groups, i.e., daily and weekly supplementation groups.
      Hemoglobin (Hb), hematocrit (Hct), serum iron, total iron binding capacity
      (TIBC), and serum ferritin were determined before the start of the study. Ferrous
      sulfate (200 mg) was given daily to the daily supplementation group and once
      weekly to the weekly supplementation group for 2 months. When post
      supplementation values of the above-mentioned parameters were determined, a
      significant improvement was observed in all parameters in both groups. It is
      concluded that once-weekly iron supplementation is as effective as daily
      supplementation for the treatment of iron deficiency anemia. Moreover, weekly
      iron supplementation is cost effective and has no or fewer side-effects.

PMID- 15510759
TI  - Respiratory adenoviral infections in children: a study of hospitalized cases in
      southern Taiwan in 2001--2002.
AB  - Adenoviruses account for 5-10 per cent of respiratory illnesses in children. To
      analyse the clinical features and the temporal frequency in acute adenoviral
      respiratory infections in hospitalized children in southern Taiwan, a total of
      4333 children who were admitted to the Department of Pediatrics, Kaohsiung
      Municipal Hsiaokang (KMHK) Hospital, with clinical evidences of acute respiratory
      infections between January 2001 and December 2002 were studied. Adenoviruses were
      isolated from 317 patients with an isolation rate of 7.67 per cent. Serotype
      analysis was performed by polymerase chain reaction (PCR) and/or PCR-restriction
      fragment length polymorphism (PCR-RFLP) in 186 specimens. In 2001, adenovirus
      type 4 was found in the majority (57 per cent), followed by type 1.5.6 (15 per
      cent), type 2 (13 per cent), type 14 (8 per cent), type 3 (5 per cent), and type
      7 (2 per cent). In 2002, type 3 became the major type (46 per cent), whereas the
      previously predominant type 4 decreased to 6 per cent, and type 7 increased from
      2 to 19 per cent. The symptoms and signs included fever (98.7 percent), cough
      (77.6 per cent), abnormal breathing sounds (crackles and/or wheezing 23.3 per
      cent), abdominal pain (18.9 per cent), vomiting (21.8 per cent), and diarrhea
      (25.2 per cent). The mean duration of fever was 4.8 days (range 0-19 days). In
      the 186 cases in whom serotypes were analysed, pharyngitis and tonsillitis (47.8
      per cent) were the most common presentation, followed by pneumonia (25.2 per
      cent), bronchitis (12.9 per cent), and pharyngoconjunctival fever (PCF) (7.6 per
      cent). Children between 4 and 8 years old were the most common group of patients
      with respiratory adenoviral infections. Our patients all had good prognosis. This
      adenoviruses molecular epidemiological study provides information that helps
      physicians in clinical differential diagnosis and treatment of respiratory
      adenoviral infection in children in southern Taiwan.

PMID- 15510760
TI  - Assessment of gestational age in the Cameroonian newborn infant: a comparison of
      four scoring methods.
AB  - A clinical assessment of gestational age using four different methods was
      performed in the same population of 358 Cameroonian newborn infants with the aim
      of determining the most applicable in the local context. Method applicability was
      compared in terms of validity, accuracy, reliability, and ease of administration.
      The gestational age ranged from 25 to 44 weeks. The infants were evaluated within
      72 h from birth, using the scoring methods of Farr (FSM), Dubowitz (DSM), Ballard
      (New Ballard Score--NBS) and Eregie (ESM). The DSM was the most valid with a 93
      per cent agreement within +/-2 weeks of gestational age by dates followed by the
      ESM with 92.4 per cent. The NBS and the FSM showed lower validity of 85.6 per
      cent and 78.3 per cent respectively. The ESM was the most accurate with a mean
      difference (MD) in weeks (+/-1 SD) between gestational age by method and
      gestational age by dates of 0.259+/-1.376, followed by the NBS with 0.355+/-1.51.
      The DSM was fairly accurate with a MD of 0.500+/-1.31, and the FSM the least
      accurate with a MD of 1.228+/-1.495. The DSM was the most reliable with a high
      correlation coefficient (r) of 0.94. The NBS and the ESM had comparable
      reliability with correlation coefficient of 0.93 each. The easiest to administer
      was the ESM, completed in an average of 41 s, followed by the FSM in 1 min 22 s.
      The NBS was completed in 2 min 48 s and the DSM in 4 min 28 s. We concluded that
      the Eregie model has comparable validity and reliability to the Dubowitz score
      but is more accurate, simple, and very easy to administer. It is therefore
      recommended where the workload is heavy and health personnel limited, as is the
      case in developing countries.

PMID- 15510761
TI  - Incidence of child and adolescent abuse among incarcerated females in the
      northeast of Brazil.
AB  - The intergenerational transmission of violence and the tendency for abused and
      neglected children to become abusers, delinquents, and violent offenders in their
      adult life is an important field to be understood. It is also important to
      understand these backgrounds to guide future preventative interventions. Through
      a cross-sectional study, the occurrence of abuse during childhood and adolescence
      of adult women incarcerated in a female state prison at Recife in northeast
      Brazil was investigated. Among 219 prisoners, 190 accepted to join the research;
      149 were young women (23-27 years) with severe educational deficiency. Living in
      poor socioeconomical conditions with problematic and violent familiar relations,
      116 (61 per cent) left home at the end of their adolescence and the same number
      reported having been abused (p < 0.000015). There was a statistical significance
      between the abuses suffered and witnessed by the subjects and the perpetration of
      abuse against children and adolescents by themselves (p < 0.0022 and p <
      0.0000049). Parents were the most frequent perpetrators (37.4 per cent). Sexual
      activity and use of legal and illegal drugs occurred early in adolescence. The
      group also had a family history of violence. Based on the analysed data of this
      studied group, the authors assumed that the abuse suffered in childhood and
      adolescence of these women drove them to be abusers in adult life and could have
      been a predictive marker for their conduct disorders and subsequent criminal
      behavior.

PMID- 15510762
TI  - Neonatal tetanus in the South-Eastern region of Turkey: changes in prognostic
      aspects by better health care.
AB  - Neonatal tetanus is an important health problem with an estimated 500,000 deaths
      per year worldwide, particularly in developing countries. We analysed 56 cases of
      neonatal tetanus (NNT), retrospectively, who were admitted to Diyarbakir Children
      State Hospital between 1994 and 2001. In 1998 an intervention in a childcare
      intensive unit was conducted, which included a nurse education programme,
      increasing the number of nurses and other health staff, and more qualified
      management of cases. The mean age of patients was 7.9 days at admission, and the
      male:female ratio was 1:6. Eleven per cent of the cases had body weight under
      2500 g. The mean hospitalization period was 9.9 days. All patients were born at
      home without medical help and 28.6 per cent were from urban areas. The case
      fatality rate that was formerly 88.5 per cent, decreased to 53.6 per cent by the
      intervention conducted in 1998. Based on our findings, we can say that improved
      hospitalization conditions and intensive care may reduce mortality. Enforcing
      preventive policies both in rural and urban areas is of great importance in the
      least developed regions.

PMID- 15510763
TI  - Outbreak of dengue in Mumbai and predictive markers for dengue shock syndrome.
AB  - An alarming rise of dengue has been seen in Mumbai during the post-monsoon
      season. We undertook this prospective study in the pediatric wards and pediatric
      intensive care unit of B. J. Wadia Hospital for Children between 27 August 2003
      and 10 October 2003 to determine the clinical features, laboratory abnormalities,
      and outcome of children affected with dengue and to determine the predictive
      markers for dengue shock syndrome. Fifty-one suspected dengue cases were tested
      for positivity of dengue by determination of dengue IgM antibodies by ELISA test.
      These positive cases were analysed for common clinical features, laboratory
      derangements, and outcome. Patients were subdivided into three subgroups: dengue
      fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS) as
      per WHO classification. Predictive markers for DSS were also determined. Thirty
      nine patients had a positive dengue IgM titre, 20 patients had DHF, 18 patients
      had DSS, and one patient had DF The mean age of presentation was 4.9 years.
      Fever, hepatomegaly, vomiting, bleeding tendencies, erythematous rash,
      thrombocytopenia, elevated liver enzymes, and deranged PT and PTT were the
      predominant clinical and laboratory features. Predictive markers for DSS were
      younger age at onset, altered sensorium, paralytic ileus, and significantly
      deranged PT. Patients with DSS also had a longer recovery period and required
      more supportive management in the form of component therapy and ionotropic
      support. All three patients who died belonged to the DSS subgroup with case
      fatality rate for DSS being 16.6 per cent. None of the patients in the DHF or DF
      subgroup died. Endemicity of dengue fever is on the rise in Mumbai with increased
      incidence among children. Appropriate investigations, strict monitoring and
      prompt supportive management can reduce mortality in dengue. Predictive markers
      of DSS can reduce the mortality if promptly treated. Also prevention of
      transmission by mosquito control and maintaining water sanitation is required to
      effectively control this epidemic.

PMID- 15510764
TI  - Study of infant feeding practices: factors associated with faulty feeding.
AB  - KEM Hospital, Mumbai was recognized as a 'baby-friendly' hospital on the basis of
      adherence to the 'Ten steps to successful breastfeeding', a decade ago. This
      study was undertaken to determine the sustainability of the programme in terms of
      feeding practices undertaken by the mothers on the basis of advice given to them.
      A total of 92.11 per cent of the infants up to 6 months of age received exclusive
      breastfeeding. Timely complementary feeding rate was 95 per cent. Thus
      interventions used in the programme seem sustainable.

PMID- 15510765
TI  - Rebound bilirubin measurement is not required for hyperbilirubinemia regardless
      of the background attributes of newborns.

PMID- 15510766
TI  - Specific pneumococcal antibodies in a population of children with recurrent
      infections from Neiva, Huila, Colombia.

PMID- 15510767
TI  - Vitamin A supplementation to children in India from controversies to consensus.

PMID- 15510768
TI  - Opportunities for improving the quality of nutritional services in the national
      health system in Mozambique: findings from Manica Province.
AB  - In Mozambique, nutritional deficiencies are a major constraint to development.
      The present study assessed health providers' nutritional knowledge and practices
      in the national health system. The following were conducted: 30 interviews with
      health providers; 326 interviews with clients (129 with women attending prenatal
      consultations, 50 with women attending postnatal consultations, and 147 with
      mothers attending child consultations); and 190 observations of client-provider
      interactions (73 with pregnant women, 39 with post-partum women, and 78 with
      mothers attending child consultations). The findings of the study highlighted the
      extent of missed opportunities during routine prenatal, postnatal, and childcare
      consultations for the delivery of key services for the prevention and treatment
      of highly prevalent nutritional deficiencies among the children and women
      'covered' by the health system. These findings can aid the development of
      policies and programmes aimed at strengthening the delivery of essential low
      cost/high-impact nutritional services through the national health system in
      Mozambique.

PMID- 15510770
TI  - Tragedy in home care.

PMID- 15510771
TI  - Unique roles complementary.

PMID- 15510772
TI  - Unique roles complementary.

PMID- 15510773
TI  - Extending a good idea.

PMID- 15510774
TI  - Words to live by.

PMID- 15510775
TI  - Support for informatics.

PMID- 15510776
TI  - Support for informatics.

PMID- 15510778
TI  - Caring, for a renewed care.

PMID- 15510777
TI  - Recalling Weija clinic.

PMID- 15510779
TI  - Elise's Journal.

PMID- 15510780
TI  - First steps in career planning.

PMID- 15510781
TI  - How nurses are conceptualized in healthcare reform literature.
AB  - Nurse coping, empowerment and job satisfaction are conceptualized as modifiable
      from organizational and psychological perspectives. Questions about what stories
      nurses tell themselves to live by and to shape healthcare reform have not been
      part of thinking about the impact of restructuring on nurses.

PMID- 15510783
TI  - An anchor in turbulent times.

PMID- 15510782
TI  - Handwashing compliance.
AB  - Undeniably, handwashing remains the single most effective and cost-efficient
      method for preventing and reducing the transmission of nosocomial infections. Yet
      the rates and outbreaks of nosocomial infections in Canadian and international
      healthcare institutions continue to increase. Shaikh Khalifa Medical Center
      developed and implemented a multidisciplinary approach to address the challenges
      of handwashing compliance among nurses and healthcare workers in its workplace
      setting. Supported by evidence-based research, the approach consisted of three
      components: collaboration, implementation and evaluation. The use of the alcohol
      based hand rub sanitizer or "solution" was integral to the multidisciplinary
      approach. Ongoing education, communication and a committed leadership were
      essential to promote and sustain handwashing compliance.

PMID- 15510784
TI  - New president's vision.

PMID- 15510785
TI  - Canadian nurses forge partnership in fight against HIV/AIDS.

PMID- 15510786
TI  - Above and beyond.

PMID- 15510787
TI  - Clinical observation on acupuncture treatment in 35 cases of diabetic
      gastroparesis.
AB  - In order to observe the therapeutic effects of acupuncture on diabetic
      gastroparesis, 80 cases were divided randomly into 3 groups. In addition to the
      routine treatment for diabetes, 35 cases in the treatment group were additionally
      treated with acupuncture, and 25 cases in the control group 1 with domperidone,
      while 20 cases in the control group 2 with nothing. The three groups were all
      observed for 25 days. The results turned out to be that the total effective rate
      in the treatment group reached 94.2%, that in the control group 1, 72%, and in
      the control group 2, 40%, the treatment group showing a better therapeutic effect
      than the other two control groups (P < 0.05, P < 0.01). It can be concluded that
      in addition to the routine treatment for controlling blood sugar, acupuncture can
      give quite good therapeutic effects on diabetic gastroparesis.

PMID- 15510788
TI  - Auricular-plaster therapy for treatment of IBS.

PMID- 15510789
TI  - Two hundred cases of insomnia treated by otopoint pressure plus acupuncture.

PMID- 15510790
TI  - One hundred and six cases of chronic gastritis treated by acupuncture.

PMID- 15510791
TI  - Clinical study on electro-acupuncture treatment for 30 cases of mental
      depression.
AB  - To observe the clinical therapeutic effects of electro-acupuncture therapy for
      mental depression, 30 cases were treated by electro-acupuncture on Baihui (GV20),
      Yintang (EX-HN3) and the differential points. Maprotiline was used in the control
      group of 31 cases. After the treatment, the scores in HAMD for both groups were
      found to be obviously decreased as compared with those before the treatment (P <
      0.01), without significant between-group differences (P > 0.05). The total
      effective rate in the treatment group was 96.7%, and that of the control group
      was 90.3%, showing no significant between-group differences (P > 0.05). After the
      treatment, the two groups all showed obvious decrease in the TCM symptomatic
      integrals (P < 0.01), with significant between-group differences (P < 0.05), the
      integral of the treatment group showing obvious superiority to that of the
      control group. And the decrease of the Asberg scores testing the side effect of
      antidepressants of the treatment group was obviously superior to that of the
      control group. After the treatment, the cortisol (CORT) content and the
      endothelin-1 (ET-1) content of the two groups were all obviously decreased (P <
      0.01), and basically turned to normal, without significant between-group
      differences (P > 0.05). CONCLUSION: Electro-acupuncture, therapy can produce the
      same clinical therapeutic effect as that produced by the tetracyclic drug
      maprotiline, giving less side effect and better symptomatic improvement.

PMID- 15510792
TI  - Two hundred and fifty-eight cases of hemoptysis treated by injection of vitamin
      K3 into Chize point.
AB  - Injection of vitamin K3 into Chize (LU 5) was used from 1980 to 1992 in 258
      inpatients suffering from diseases of the respiratory system accompanied with
      hemoptysis. As a result, the effective rate was 83% for mild hemoptysis and 72.1%
      for moderate hemoptysis in the treatment group, as compared to 48.5% and 45.2%
      respectively in control group A, and to 83.8% and 75% in control group B. There
      was a significant difference between the treatment group and control group A (P <
      0.01). However, the effective rate was only 31.8% for severe hemoptysis in the
      treatment group, as compared to 81.3% in control group B with a significant
      difference. It is therefor concluded that injection of vitamin K3 into Chize is a
      good therapy for mild or moderate hemoptysis but not for severe cases.

PMID- 15510793
TI  - Combined use of acupuncture and pharmacotherapy for treatment of auditory
      hallucination.

PMID- 15510794
TI  - The needling technique and clinical application of point Zhibian.
AB  - Point Zhibian (BL 54) is often used for treatment of lumbago and scelalgia,
      flaccidity and arthralgia of the lower limb, constipation and dysuria, and
      hemorrhoid. As for the needling, the direction of the needle tip may vary,
      generally in three directions: 1) along the channel itself, 2) pointing to the
      genitals, and 3) pointing to the anus, the purpose of which is "leading qi to the
      diseased area" so as to obtain "effectiveness upon the arrival of qi". This point
      can also be used in combination with moxa stick, cupping, and point injection
      according to the individual conditions. However, only by differential
      application, can this point produce better therapeutic effects.

PMID- 15510795
TI  - Clinical analysis for the acupuncture treatment in 42 cases of gouty renal
      damage.
AB  - OBJECTIVE: To observe the therapeutic effects of acupuncture on gouty renal
      damage. METHOD: 72 cases of gouty renal damage were randomly divided into a
      treatment group of 42 cases and a control group of 30 cases to observe the
      therapeutic effects and the changes in 24-hour urinary protein content, blood
      creatinine, uric acid and urea nitrogen in blood before treatment and one month
      after treatment. RESULTS: The total effective rate in the treatment group reached
      95.24%, which was remarkably higher than 63.33% in the control group. After one
      month of treatment, the indexes were found reduced in both groups, but the
      reduction rate in the treatment group was obviously superior to that in the
      control group. CONCLUSION: The patients with repeated attacks of gout may have a
      higher possibility to suffer from renal damage. Therefore, attention should be
      paid to its early diagnosis and treatment. Acupuncture may exert good therapeutic
      effects on early gout complicated with renal damage by adjusting the metabolism
      and improving the renal function.

PMID- 15510796
TI  - Dr. Shi Yanqing's experience in acupuncture treatment of paralysis agitans.

PMID- 15510797
TI  - Mind-refreshing acupuncture therapy for facial spasm, trigeminal neuralgia and
      stubborn facial paralysis.
AB  - It has been proved by clinical experiment that needling at Fengchi (GB 20), Wangu
      (GB 12) and Tianzhu (BL 10) can markedly improve the blood supply to the
      vertebral basilar artery, increase the cerebral blood flow, and relax the spasm
      of the vascular smooth muscles. The combined use of Shangxing (GV 23) and Yintang
      (EX-HN3) can give the effects of resuscitating and tranquilizing the mind,
      dispelling wind, dredging the channels, and relieving spasm and pain. In short,
      the above therapy may turn the pathological state into a normal physiological
      state, and bring a quicker recovery for patients with facial spasm, trigeminal
      neuralgia and stubborn facial paralysis.

PMID- 15510798
TI  - Treatment of primary hypotension by electroacupuncture at Neiguan and Gongsun--a
      report of 100 cases.

PMID- 15510799
TI  - Fifty cases of external humeral epicondylitis treated by moxibustion and point
      injection.
AB  - OBJECTIVE: To observe the therapeutic effects of moxibustion and point-injection
      on external humeral epicondylitis. METHOD: The disease is treated with the
      combined method of moxibustion and point-injection of the Compound Dan Shen
      Injectio and Ye Mu Gua Injectio RESULTS: 30 of the total 50 cases were cured, 18
      cases were improved, and 2 cases were with no effect. The total effective rate
      was 96%. CONCLUSION: The combined method of moxibustion and point-injection is a
      cure indicated for external humeral epicondylitis.

PMID- 15510800
TI  - Acupuncture treatment for 87 cases of facial paralysis.

PMID- 15510801
TI  - Dr. Shang Zhaokui's experience in acupuncture treatment of three obstinate cases.

PMID- 15510802
TI  - Nephrotic syndrome and the TCM treatment.

PMID- 15510803
TI  - A clinical study on treatment of senile psoriasis by replenishing qi to activate
      blood--a report of 40 cases.
AB  - 40 cases of senile psoriasis were treated by the therapeutic principle of
      replenishing qi to activate blood, and the changes of T lymphocyte subgroups and
      indexes of haemorheology were observed. The results showed that CD4 was
      significantly increased, CD8 significantly decreased, and the CD4/CD8 ratio
      significantly raised; and that the specific viscosity of whole blood at high
      shearing rate, and at low shearing rate, the specific viscosity of plasma, packed
      cell volume, and fibrinogen all significantly decreased after treatment. It is
      therefore concluded that the therapeutic method of replenishing qi to activate
      blood can exert an effect of improving immunologic function and blood
      circulation.

PMID- 15510804
TI  - Medicinal herbs used in pairs for treatment of 98 cases of chronic gastritis.
AB  - OBJECTIVE: Chronic gastritis was treated with herbal pairs in order to reduce the
      side effects and raise the therapeutic effects. METHOD: The outpatients were
      randomly divided into a treatment group treated with herbal pairs and a control
      group treated with Banxia Xiexin Tang (Pinellia Decoction for Purging the Stomach
      fire). RESULT: The total effective rate in the treatment group was 96%, higher
      than that in the control group (P < 0.05). CONCLUSION: With the basic theory of
      traditional Chinese medicine as guiding principles, herbal pairs have two-way
      regulatory effects, that is, reducing the side effects and raising the
      therapeutic effects.

PMID- 15510805
TI  - Dr Ji Wenhuang's experience in TCM treatment of thyropathy.

PMID- 15510806
TI  - Prof. Luo Zhiqiang's experience in treating cervical vertigo.

PMID- 15510807
TI  - Effects of acupuncture on hemorheology, blood lipid content and nail fold
      microcirculation in multiple infarct dementia patients.
AB  - Forty-six cases of multiple infarct dementia (MID) in the treatment group were
      treated by acupuncture with the principle of supplementing the inferiority to
      clear the superiority and regulating spirit to invigorate intelligence. Changes
      of the blood lipid content, hemorheological indexes and nail fold
      microcirculation in the treatment group were compared with those in the randomly
      assigned control group. The data collected showed that the changes in the
      treatment group were remarkable, and part of them were superior to their
      counterparts obtained in the control group by statistical analysis. It is
      indicated that acupuncture can effectively regulate the affected hemodynamic
      state in MID.

PMID- 15510808
TI  - Effects of Chinese herbal medicine on bone structure and function.
AB  - This study examined the effects of four-months of treatment using Chinese herbal
      Shu Di Shan Zha Formula on bone health. Fourteen Australian menopausal women
      participated in this paired study and completed all the tests at the
      commencement, 4th month (when the treatment group and control group cross over)
      and the 8th month (end) of the study. Data from bone structure and function tests
      (broadband ultrasonic attenuation--BUA and velocity of sound--VOS), biomarkers of
      bone turnover (osteocalcin--OSTN and urinary pyridum crosslinks--PYR and D-PYR)
      were collected from each subject. Results showed that Shu Di Shan Zha Formula was
      able to affect the level of BUA, and reduce the level of D-PYR in menopausal
      women.

PMID- 15510809
TI  - Effects of the Chinese drugs for activating blood circulation on plasma TXB2 and
      6-keto-PGF1alpha contents in rabbits with glucocorticoid-induced femoral head
      necrosis.
AB  - In the femoral head necrosis model rabbit induced by endotoxin combined with
      methylprenisolone, the dynamical changes of plasma TXB2 and 6-keto-PGF1alpha
      contents were observed. As a result, microscopic examination showed that in the
      model group, bone trabeculae became fine, empty bone lacunae increased, and
      osteoblasts in number decreased; the ratio of TXB2 and 6-keto-PGF1alpha was out
      of balance, and these changes worsened gradually with the lapse of time; Compound
      Sheng Mai Cheng Gu Capsules could reverse femoral head necrosis, protect the
      vascular endothelial cells, recover the balance of TXB2 and 6-keto-PGF1alpha. It
      is concluded that the hormone-induced femoral head necrosis is closely related
      with blood stasis, and that the Chinese drugs for activating blood circulation
      and removing blood stasis can prevent the femoral head from development of
      necrosis.

PMID- 15510810
TI  - Acupuncture treatment of tinnitus.

PMID- 15510811
TI  - [Extrapleural pneumonectomy for thoracic malignancies].
AB  - Extrapleural pneumonectomy has been used by thoracic surgeons in the treatment of
      malignant pleural mesothelioma as well as other pleural diseases, such as
      tuberculous empyema. Recently, this operative procedure has been also
      sporadically applied for the treatment of carcinomatous pleuritis of lung cancer
      and/or invasive thymoma in some institutions. We performed this operation in 24
      patients with thoracic malignancy: 15 patients with carcinomatous pleuritis of
      primary lung adenocarcinoma (6 patients with T4N0 disease, 2 with T4N1, and 7
      with T4N2), 3 patients with stage IV a thymoma, and 6 patients with malignant
      pleural mesothelioma (2 patients with stage II disease, 3 with stage III, and 1
      with stage IV). All patients survived the operation and were discharged from the
      hospital. Major complications were intrathoracic hemorrhage and empyema in 2
      patients each. The median survival time and 5-year survival rate of lung cancer
      patients were 34 months and 45.5%, respectively. All patients with thymoma are
      alive now without disease 9 to 133 months after operation. All patients with
      malignant pleural mesothelioma except 1, who lately underwent this treatment,
      died of disease from 15 to 27 months after surgery. Our results indicate that
      carefully selected patients with carcinomatous pleuritis of lung cancer and
      thymoma may be candidates for extrapleural pneumonectomy for cure. Nevertheless,
      the ultimate value of this surgical treatment should be ascertained in a
      prospective study with a large number of patients.

PMID- 15510812
TI  - [Extrapleural pneumonectomy for malignant pleural mesothelioma and primary lung
      cancer].
AB  - The extrapleural pneumonectomy for 6 patients with malignant pleural mesothelioma
      and 2 patients with primary lung cancer have been performed in our unit in those
      10 years. Range of the age was 48-57 year-old. All of them were male and have
      been in occupational asbestos exposure. The mean survival time after extrapleural
      pneumonectomy was 620 days. In those, we experienced a case of malignant
      mesothelioma with excellent reduction by induction therapy of cisplatin+docetaxel
      hydrate, who underwent the extrapleural pneumonectomy continuously. We mentioned
      more over about the role of extrapleural pneumonectomy for primary lung cancer
      with pleural dissemination, and intrapleural perfusion hyperthermo-therapy for
      malignant mesothelioma.

PMID- 15510813
TI  - [Extrapleural pneumonectomy of malignant pleural mesothelioma].
AB  - We analyzed 7 patients with malignant pleural mesothelioma who underwent
      extrapleural pneumonectomy. Six men and a woman had a mean age of 65 years old.
      The postoperative mortality rate was 14% (1 death) and morbidity, 43% (3 cases).
      According to staging of International Mesothelioma Interest Group, 2 patients had
      stage I disease, 1 did stage II, 3 did stage III and 1 did stage IV. Local
      recurrences were found in 3 patients and metastasis in 2. In patients with local
      recurrences, 2 had irradiation with chemotherapy and 1, irradiation. In patients
      with recurrences of metastasis, 1 had chemotherapy and 1, supportive care. Seven
      patients with extrapleural pneumonectomy and 10 without surgery had median
      survivals of 16 months and 10 months, 1-year survival rates of 71% and 40% and 2
      year survival rates of 57% and 0% respectively (p=0.071). Extrapleural
      pneumonectomy with adjuvant therapy could be effective treatment for malignant
      pleural mesothelioma.

PMID- 15510814
TI  - [Extrapleural pneumonectomy for malignant pleural mesothelioma].
AB  - Standard treatment for malignant pleural mesothelioma (MPM) has not been proved
      yet. However, it has been recognized that extrapleural pneumonectomy (EPP) is a
      treatment of choice for epithelial MPM when combined with adjuvant therapies
      though EPP may frequently cause fetal complications. We report 5 cases of MPM
      with EPP, including 1 with good prognosis. Sixteen patients with MPM were
      admitted to our hospital between 1988 and 2003. Five patients underwent EPP,
      among which 4 were male and 1 female with ages from 46 to 61 years old.
      Histologically, 3 of them were epithelial and 2 were biphasic. Those with
      biphasic experienced acute respiratory failure and empyema, and died 81 days and
      8 months after the surgery respectively. Among those with epithelial MPM, 2 are
      alive with no recurrence at 129 and 29 months after the surgery, and the other,
      followed by postoperative radiotherapy, died at 12 months. More cases with EPP or
      randomized controlled trials regarding EPP are necessary to evaluate efficacy of
      EPP for MPM.

PMID- 15510815
TI  - [Extrapleural pneumonectomy after hyperthermo-chemotherapy for the lung cancer
      patients with malignant pleural effusion].
AB  - The prognosis of the lung cancer patients with malignant pleural effusion is
      extremely poor. Intrapleural perfusion hyperthermo-chemotherapy for the treatment
      of malignant pleural effusion was performed in 120 lung cancer patients and
      showed better prognosis than conventional treatment. After successful local
      control by hyperthermo-chemotherapy, extrapleural pneumonectomy was performed in
      8 patients with clinical N 0 or N 1 and M 0 lung cancer. All patients survived
      for more than 1 year. The only 1 patient survived for more than 3 years and 3
      months without recurrence. Almost all patients who died within 2 years had
      pathological n 2, carcinomatous pericarditis, cancer invasion beyond extrapleural
      space and so on. Extrapleural pneumonectomy after hyperthermo-chemotherapy can be
      a choice of surgical treatment if the n 2 disease, pericarditis, and extrapleural
      invasion of disseminated cancer cells should be excluded precisely.

PMID- 15510816
TI  - [Multimodality therapy for diffuse malignant pleural mesothelioma].
AB  - Despite the rising incidence of diffuse malignant pleural mesothelioma (MPM),
      there is still no standard treatment for this disease, and the prognosis for
      patients remains poor. Recently, long-term survival has been reported when
      multimodality therapy is used, combining extrapleural pneumonectomy with
      perioperative chemotherapy and/or radiotherapy in highly selected patients. We
      report a case of a patient who presented with MPM, accompanied by a large
      malignant pleural effusion and pneumothorax, who was successfully treated with
      combination therapy. After being diagnosed with epithelial type MPM using
      thoracoscopic surgery, the patient underwent extrapleural pneumonectomy.
      Examination of the surgical specimen revealed invasion of the chest wall muscle
      and fat, as well as several positive mediastinal lymph nodes. The patient
      received 2 courses of postoperative chemotherapy using cisplatin and gemcitabine.
      He is currently alive and has been disease-free for 2 years.

PMID- 15510817
TI  - [Pleuropneumonectomy for pulmonary tuberculosis and chronic tuberculous empyema].
AB  - Surgical intervention is often necessary to treat either the active pulmonary
      tuberculosis or its sequelae such as destroyed lung, tuberculous empyema, and
      bronchial stenosis. Pleuropneumonectomy, which has been reported to be associated
      with high mortality and morbidity, is performed when the pleural space is
      completely obliterated due to previous inflammation or when preoperative empyema
      is complicated. In this article we report 3 patients receiving
      pleuropneumonectomy for pulmonary tuberculosis or chronic tuberculous empyema in
      recent 3 years. The mean operation time is 5 hours and 56 minutes, and the mean
      volume of intraoperative bleeding amounted to 1,417 ml. Autologous blood
      transfusion was prepared for all 3 patients and transfused them during the
      operation. No mortality, but postoperative complications were seen in 2 patients
      (67%) with a history of diabetes mellitus. They were sternum infection and
      bronchopleural fistula, which were successfully treated conservatively. Diabetes
      mellitus is thought to be a major risk factor for not only tuberculous disease
      itself, but also postoperative morbidity. As for surgical techniques, wide skin
      incision with multiple thoracotomy is necessary to keep a good operative field,
      and special care must be taken for great vessels and nerves at extrapleural
      dissection. We conclude that pleuropneumonectomy is relatively risky but
      effective surgical procedure for adequately selected patients with destroyed lung
      and tuberculous empyema.

PMID- 15510818
TI  - [Extrapleural completion pneumonectomy combined with chest wall resection for
      complex aspergilloma].
AB  - Completion pneumonectomy for complex aspergilloma remains challenging for
      thoracic surgeons. This pneumonectomy procedure often requires extrapleural
      dissection. Although extrapleural dissection is effective in preventing
      intraoperative contamination of the operative field, it is associated with
      massive bleeding. In addition, when the pleura has been severely thickened, it is
      difficult to conduct extrapleural dissection. We herein report 2 patients who
      underwent an extrapleural completion pneumonectomy combined with chest wall
      resection. In this technique, we avoided extrapleural dissection where dense
      pleural adhesions existed. Instead, we performed an en-bloc chest wall resection.
      This technique can decrease the amount of bleeding and prevent contamination of
      the operative field. It can also reduce the size of post-pneumonectomy space, and
      decrease the chance of post-pneumonectomy empyema and bronchial stump fistula. We
      advocate that extrapleural completion pneumonectomy combined with chest wall
      resection be considered in case that extrapleural dissection is extremely
      difficult.

PMID- 15510819
TI  - [An operative approach of extrapleural pneumonectomy].
AB  - We present a case of breast cancer with pleural metastasis and empyema treated
      with extrapleural pneumonectomy. We showed the some of technically important
      points for this operation. The careful preparation was needed to prevent
      hemorrhage from such as great vessels, bronchial arteries and intercostal
      arteries. Especially in this surgical procedure, we should select the best
      approach method to have enough surgical field for complete tumor resection. We
      suggest that we should make additional thoracotomy and skin incision immediately
      when we feel the surgical field is not wide enough during the operation. The
      extrapleural pneumonectomy is one of the most highly invasive operation in
      general thoracic surgery, so careful perioperative managements should be
      required.

PMID- 15510820
TI  - [Diaphragm reconstruction after extrapleural pneumonectomy].
AB  - Extrapleural pneunonectomy with resection of the diaphragm only offers acceptable
      therapeutic results in patients with malignant diseases of the pleura and the
      lung. The standard procedures for diaphragm reconstruction consist of the use of
      biomaterials and prosthetic patches. We retrospectively reviewed techniques and
      results in 4 patients where the pedicled latissimus dorsi flap, the expanded
      polytetrafluoroethylene (ePTFE) sheet and the composite mesh sheet consisting of
      the ePTFE sheet and 2 layers of polypropylene mesh sheets were successfully used
      to replace the resected diaphragm. When we evaluated such biomaterials and
      prosthetic patches, the ePTFE sheet was superior in the time of reconstruction to
      other materials although it was expensive. The pedicled latissimus dorsi flap did
      not apply to patient with poor muscle volume. In conclusion, the ePTFE sheet
      widely applies to every patient who requires diaphragm reconstruction after
      extrapleural pneumonectomy.

PMID- 15510821
TI  - [Removal of the intrapleural hematoma after extrapleural pneumonectomy].
AB  - Three cases of pleuropneumonectomy, which have been performed in our institution
      between 1996 and 2003, are studied. All of them received re-thoracotomy to remove
      intrapleural hematoma for prolonged high fever, anemia and high level of CRP.
      Post re-operative courses were satisfactory without any signs of infection. The
      residual intrapleural hematoma sometimes causes pyothorax and would be an
      obstacle to the intrapleural instillation of anticancer medications. The removal
      of the hematoma should be scheduled at an early period after the
      pleuropneumonectomy.

PMID- 15510822
TI  - [Chronic traumatic aneurysm of the thoracic aorta; report of a case].
AB  - We report a rare case of chronic traumatic aneurysm of the thoracic aorta. A 23
      year-old man flew down from the fifth floor of his apartment for an attempted
      suicide. He suffered right subdural hematoma, bilateral hemothorax, lung
      contusions, and many other traumas. He was paralyzed by the fracture and
      dislocation of the first lumbar vertebra. Posterior fixation of lumbar vertebra
      and the segmental resection of the jejum were performed on the first and third
      day, respectively. He recovered well; however, he complained his nocturnal
      dyspnea on the forty-fifth day. Detailed examinations showed that bilateral
      bronchi were compressed by the aneurysm of thoracic aorta. Elective operation was
      performed on the sixty third day. Psudoaneurysm, 5 cm in diameter, was disclosed
      in the aortic isthmus. Graft replacement was undergone with the cardiopulmonary
      bypass. His postoperative course was uneventful, and he was transferred for the
      rehabilitation of his paralysis on the eigty-eighth day.

PMID- 15510823
TI  - [Valvuloplasty for aortic regurgitation with bicuspid valve: report of a case].
AB  - A 32-year-old male patient with bicuspid aortic valve underwent valvuloplasty for
      the treatment of aortic regurgitation. The aortic regurgitation was estimated to
      be grade III based on the transthoracic echocardiography and aortography
      findings. Transesophageal echocardiography showed prolapse of the conjoined
      leaflet. At surgery, the valvuloplasty consisted of triangular resection and re
      suture of the prolapsed larger leaflet, and subcommissural annuloplasty. The
      degree of the aortic regurgitation decreased to very slight degree after the
      repair. The peak pressure gradient across the repaired aortic valve was 8.8 mmHg.
      The patient was discharged without any complications. The bicuspid aortic valve
      demonstrating aortic regurgitation seems to be repairable. As a result, the
      valvuloplasty is indicated for such patients, especially for young patients.

PMID- 15510824
TI  - [Primary right ventricular malignant fibrous histiocytoma; report of a case].
AB  - Primary malignant fibrous histiocytoma located in the right side of the heart is
      extremely rare. We reported a case with literal reviews. A 71-year-old woman was
      admitted of faintness due to hypotension and marked edema of her lower extremity.
      With no time she was deteriorated into cardiogenic shock. Echocardiography
      demonstrated a tumor like mass which occupied her whole right ventricular cavity.
      Emergency tumor resection was carried out because of her status. Histological and
      immunohistochemical studies revealed the tumor was malignant fibrous
      histiocytoma. She died of pulmonary failure on nineteenth day after surgery.

PMID- 15510825
TI  - [Mediastinal seminoma difficult to differentiate from thymoma through
      preoperative biopsy; report of a case].
AB  - A case of a 36-year-old male patient with mediastinal seminoma is presented. He
      consulted a physician with a complaint of back pain and an abnormal shadow was
      detected on chest X-ray. Chest computed tomography (CT) scan revealed a pulmonary
      nodule and an anteriormediastinal mass. Preoperative percutaneous needle biopsy
      suggested that the tumor was similar to thymoma. Complete surgical excision of
      the mediastinal mass was performed. Immunohistochemical studies showed positive
      staining of the tumor cells with placental alkaline phosphatase. The final
      diagnosis was seminoma. Additional postoperative chemotherapy (cisplatin +
      etoposide) was done. He is alive and well 34 months after the operation.

PMID- 15510826
TI  - [Secondary abnormal development of the bronchial artery: report of a case].
AB  - A 65-year-old man was admitted to our hospital because of massive hemoptysis. The
      patient had suffered from pneumonia since 1999, but he had refused to undertake
      further examinations. In 2002, the patient was transferred to our emergency room
      because of massive hemoptysis. Following endotracheal intubation, the patient
      underwent bronchial artery embolization. The X-ray and computed tomography (CT)
      films on admission revealed localized bronchiectasis in the left upper lung.
      Bronchoscopic findings revealed massive bleeding from the left upper bronchus.
      Bronchial arteriography of the left bronchial artery showed peripherally
      hypervascular finding in the left upper lobe. A segmentectomy of the left upper
      division was performed as a radical therapy for localized lesions with massive
      hemoptysis. The pathological diagnosis was secondary abnormal development of the
      bronchial artery. We speculated that massive hemoptysis had occurred probably due
      to infection in the focus.

PMID- 15510827
TI  - [Primary malignant lymphoma of the rib; report of a case].
AB  - We experienced a rare case of primary malignant lymphoma of the rib. The case was
      a 67-year-old female. An abnormal shadow of the chest X-ray was pointed out.
      Preoperative diagnosis was extrapulmonary lesion on the chest computed tomography
      (CT) and magnetic resonance imaging (MRI). The tumor accompanied with chest wall
      resection was done. The tumor cell was appeared in the bone marrow diffusely. The
      tumor invaded the canal of bone cortex and expanded the neighbor tissue.
      Histologically tumor was diagnosis of the malignant lymphoma, diffuse large B
      cell type, stained by negative in L 26, positive in CD 43, positive in CD 79 a,
      negative in UCHL-1, and negative in CD 3. EBV-encoded small RNAs (EBERs) and EBV
      EBNA 2 was negative. This tumor was not able to proved to Epstein-Bar virus.

PMID- 15510828
TI  - [Acute myeloid leukemia with Aspergillus tracheobronchitis after allogeneic
      peripheral blood stem cell transplant].
AB  - A 51-year-old female with acute myeloid leukemia was admitted to our hospital in
      December 2001. Though she had undergone two courses of induction chemotherapy
      (idarubicin hydrochloride + cytarabine), she failed to achieve a complete
      remission. In April 2002, while in non-complete remission, she subsequently
      underwent total body irradiation (TBI) and treatment with cyclophosphamide (CY)
      and etoposide (VP-16) before receiving an allogeneic peripheral blood stem cell
      transplant from her HLA-identical brother. For graft-versus-host disease (GVHD)
      prophylaxis, she was given tacrolimus and methotrexate. The infused CD34 positive
      cells provided 8.1 x 10(6) cells per kg. Engraftment was obtained on post
      transplant day 14, and there was no evidence of clinical acute GVHD. The use of
      tacrolimus was discontinued on post-transplant day 60. As there was no occurrence
      of clinical acute GVHD, the patient received a donor lymphocyte infusion (CD3
      cells 0.57 X 10(7) cells per kg) on post-transplant day 105. On day 132, however,
      she complained of coughing and fever, and on day 135, she was admitted to our
      hospital again for dyspnea. A CT scan demonstrated ground-glass opacity in the
      right pulmonary lobe. After considering her clinical course, symptoms, blood gas,
      CT scans, etc., we suspected interstitial pneumonia. The dyspnea progressively
      worsened, however, and despite the use of mechanical ventilation from day 143,
      the patient died on day 149. From the day she was admitted till the day she was
      intubated, she was unable to produce sputum. Autopsy findings revealed yellow
      white tracheal pseudomembranes, as well as Aspergillus hyphae in the trachea,
      bronchus, and bilateral lungs. These findings are characteristic of Aspergillus
      tracheobronchitis. The clinical course of Aspergillus tracheobronchitis in
      allogeneic stem cell transplant recipients is, however, different from that of
      the usual invasive Aspergillus infection, and although Aspergillus
      tracheobronchitis is a very rare disease, attention should be paid to the
      possibility of its occurrence.

PMID- 15510829
TI  - [Fatal opportunistic infection following disappearance of antibodies by
      immunosuppressive therapy in a patient with acquired factor VIII inhibitor].
AB  - An 83-year-old man without history of the hemorrhagic diathesis was admitted to
      our hospital with a 4-months history of purpura and subcutaneous hematoma. He had
      an extraordinarily prolonged activated partial thromboplastin time, and his
      factor VIII (F VIII) activity level was 0.2%. A study revealed the existence of
      an IgG type anti-F VIII inhibitor at a titer of 1004 Bethesda units/ml. He
      received recombinant factor VIIa and immunosuppressive therapy with
      cyclophosphamide, prednisolone and cyclosporin, but despite this the titer of F
      VIII inhibitor remained high. Although the inhibitor disappeared after
      methylprednisolone mini-pulse therapy, the patient died of opportunistic
      infections with cytomegalovirus and pneumocystis carinii. The majority of
      patients with acquired F VIII inhibitor belong to the elderly population, and the
      standard therapeutic strategy to eliminate the acquired F VIII inhibitor has not
      been established. Those patients with high titers of F VIII inhibitor require
      particularly long term immunosuppressive therapy. Therefore, it is important to
      bear in mind treatment-related opportunistic infections in a case with a high
      titer of acquired F VIII inhibitor.

PMID- 15510830
TI  - [Second hematologic response and disappearance of the ABL gene mutant clone by
      cessation of imatinib in a CML patient with resistance to imatinib].
AB  - A seventy-six year old female patient with chronic myelogenous leukemia (CML),
      (chronic phase), was treated with imatinib and obtained a major cytogenetic
      response after 6 months of treatment. However, resistance to imatinib appeared 9
      months later due to an ABL gene point mutation, and the patient's platelet count
      and BCR/ABL positive rate had remarkably increased. We discontinued imatinib and
      used IFNalpha or hydroxyurea, resulting in the disappearance of the ABL gene
      mutation clone. After that, we obtained a secondary hematologic response with the
      administration of imatinib.

PMID- 15510831
TI  - [An abdominal follicular dendritic cell tumor in Castleman's disease].
AB  - A 57-year-old man was referred to our hospital because of elevated ALP. CT and
      MRI scans together with abdominal angiography showed multiple masses in his
      abdomen and portal vein obstruction. A diagnostic laparoscopic examination
      revealed a tumor of 3 cm x 3 cm near the portal vein and para-aortic
      lymphadenopathy. Histopathological examination of the tumor showed abnormal
      follicles with poorly formed germinal centers, scattered large spindle cells with
      proliferation of small lymphocytes, and hypervascular interfollicular tissue. The
      spindle cells were positive for follicular dendritic cell markers CD21, CD35, and
      epithelial membrane antigen. The diagnosis was made of a follicular dendritic
      cell (FDC) tumor in Castleman's disease (CD) of the hyaline-vascular type.
      Although the portal vein was obstructed by the FDC tumor, blood flow to the liver
      was retained by collateral vein. The patient did not show any response to four
      courses of CHOP therapy and died of obstructive jaundice, biliary tract infection
      and sepsis. So far, 17 cases of FDC tumor complicating CD have been reported,
      with a poor prognosis in all cases.

PMID- 15510832
TI  - [Acute myeloid leukemia presenting with obstructive jaundice and granulocytic
      sarcoma of the common bile duct].
AB  - A 55-year-old man presented with jaundice and edema of the right leg. Tests of
      the peripheral blood and bone marrow showed leukocytopenia with 6% blasts and
      38.3% of myeloperoxidase-positive blasts, respectively. Computed tomography (CT)
      scanning disclosed thickening of the common bile duct wall. Granulocytic sarcomas
      were also found at the left chest wall and the pelvic floor. Endoscopic
      retrograde cholangiopancreatography confirmed the narrowing of the common bile
      duct. Biopsy specimens of the common bile duct and pelvic masses revealed
      myeloblastic infiltration. After placement of a naso-biliary drainage tube,
      chemotherapy consisting of cytarabine (100 mg/m2/ day for 7 days) and idarubicin
      (12 mg/m2/ day for 3 days) was commenced. The dose of idarubicin was not
      modified. No serious complications, including delayed hematopoietic recovery,
      were observed after chemotherapy, and a complete remission was obtained 35 days
      later. Jaundice and liver dysfunction also gradually improved. The patient
      continues to receive consolidation therapy and remains in remission 8 months
      after the onset of his illness.

PMID- 15510833
TI  - [Eradication of adult T-cell leukemia cells and maintenance of remission by the
      graft-versus-leukemia effect after allogeneic bone marrow transplantation].
AB  - A 44-year-old man was referred to Hakodate Chuo Hospital because of progressive
      fatigue in April 2001, and was diagnosed as having adult T-cell leukemia (ATL;
      acute type). Complete remission was not obtained even with the application of
      multiple anti-leukemic agents including CHOP-V-MMV. The patient received an
      allogeneic bone marrow transplant from his HLA-identical, HTLV-I antibody
      negative sibling donor in June 2002. The conditioning regimen consisted of
      cyclophosphamide, etoposide and total body irradiation. Cyclosporine A and a
      short course of methotrexate were given as prophylaxis for graft-versus-host
      disease (GVHD). Engraftment was achieved on day 16, while ATL cells were detected
      in the peripheral blood throughout the transplantation. ATL cells were also
      detected in bone marrow on day 20. Withdrawal of the immunosuppressant induced
      the eradication of the residual ATL cells in the peripheral blood on day 24 and
      in the bone marrow on day 40. Grade III of acute GVHD developed in the bowel on
      day 40, which lasted for over 5 months and was gradually resolved by
      administration of prednisolone and tacrolimus. The patient remains in complete
      remission 23 months after the transplantation. The clinical consequence of our
      case clearly shows that a graft-versus-leukemia (GVL) effect combined with graft
      versus-host disease (GVHD) plays a curative role even in an early phase after
      bone marrow transplantation for patients with adult T-cell leukemia.

PMID- 15510834
TI  - [Cord blood transplantation supported with ex vivo expanded fraction for a
      patient with myelodysplastic syndrome and metastatic breast cancer].
AB  - Despite the promising outcomes of unrelated cord blood transplantations (UCBT) in
      pediatric recipients, the major limitation in the widespread use of cord blood
      (CB) as a source of hematopoietic stem cells (HSC), particularly in adults, is
      the physiological small number of cells. To overcome this limitation, we
      developed an ex vivo expansion system for HSC, in which CB CD34+ cells are
      cultured on feeder cells (HESS-5 cells) in the presence of cytokines (TPO, SCF
      and Flt3 ligand). A phase I/II clinical trial, approved by our institutional
      review board, has been started to assess the safety and effectiveness of this
      system. A 52-year-old woman with metastatic breast cancer and myelodysplastic
      syndrome (MDS) received a non-myeloablative preparative regimen followed by UCBT.
      On day 0, 75% of the whole CB and a fraction of CD34 negative cells were
      transplanted. The remaining 25% of the CB was CD34-selected and expanded on HESS
      5 in a non-serum media in the presence of TPO, SCF, and Flt3-L. On day 5, the ex
      vivo-expanded, CD34+ cells were transplanted. The patient received 1.83 x
      10(7)/kg of total nucleated cells and 7.7 X 10(4)/kg of CD34+ cells (expanded and
      unexpanded). No acute adverse effects were observed after the infusion of the
      cultured cells. She suffered from pneumonia on day 37, a cerebral hemorrhage on
      day 48, and died on day 50. Further studies are required to assess the
      effectiveness of this protocol.

PMID- 15510835
TI  - [Fatal acute visceral disseminated varicella-zoster virus infection in a patient
      with chronic graft-versus-host disease].
AB  - A 34-year-old woman was admitted for chronic graft-versus-host disease ten months
      after an unrelated bone marrow transplantation. Cytomegalovirus (CMV) antigenemia
      on day 5 of hospitalization was negative. Thrombocytopenia occurred on day 9.
      Laboratory findings revealed severe liver dysfunction on day 13. On day 14, the
      patient developed interstitial pneumonia and disseminated intravascular
      coagulation, and died from progressive respiratory failure. Multinucleated giant
      cells were found in the lung, liver, spleen, esophagus, pancreas and intestine
      obtained at autopsy. Varicella-zoster virus (VZV) was detected in the blood using
      the polymerase chain reaction (PCR) technique. CMV, herpes virus type 6 and
      Epstein-Barr virus were detected in the liver and lung with the PCR technique. We
      concluded visceral VZV infection was the main cause of her death because of her
      aggressive clinical course and the histology at autopsy. In this case, chronic
      GVHD and its immunosuppressive treatment resulted in her fatal VZV reactivation.

PMID- 15510836
TI  - [Emergence and decrement of Ph-negative clone with trisomy 8 in CML during
      imatinib therapy].
AB  - An increase in the presence of the Ph-negative, trisomy 8 clone has been reported
      in chronic myelogenous leukemia (CML) under imatinib therapy, but any impact of
      the clone on patient prognosis remains uncertain. We report here on a 42-year-old
      male with CML who received imatinib after failure of interferon-alpha therapy. A
      chromosomal analysis revealed 18/20 trisomy 8 in bone marrow at 10 months of
      imatinib administration. Continuing imatinib at 300 mg daily resulted in a
      decrease in the number of trisomy 8 clones as well as the disappearance of Ph
      clone. Furthermore, the patient's pancytopenia was gradually improved. Imatinib
      therapy could be continued even with the emergence of trisomy 8.

PMID- 15510837
TI  - [Complex additional chromosomal abnormalities of del(5q), del(7q), and +22 in a
      patient with acute myelomonocytic leukemia carrying inv(16)].
AB  - A 37-year-old man with acute myelomonocytic leukemia (AML) M4E who exhibited the
      complex karyotype of 5q-, 7q-, and +22 in addition to inv(16), relapsed soon
      after complete remission. As previously reported, AML M4E carrying inv(16) is
      associated with a good prognosis, even when co-occurring with chromosomal
      abnormalities, which alone are considered to have poor outcome. Cytogenetic
      prognosis studies, such as CALGB or SWOG, have reported that certain additional
      chromosomal abnormalities or complex karyotypes might affect the prognosis of
      patients with AML M4E with inv(16). Our case suggests that, in general, AML M4E
      carrying inv(16) is in the favorable risk category, while cases with additional
      chromosomal abnormalities or complex karyotypes might be classified in the poor
      risk group and thus should be given additional clinical attention.

PMID- 15510838
TI  - [Interstitial pneumonia during treatment with thalidomide in a patient with
      multiple myeloma].
AB  - A 66-year-old man was referred to our hospital for the treatment of refractory
      multiple myeloma with thalidomide. He had a history of an interstitial pneumonia
      of unknown etiology two months before admission. Eight days after starting 200
      mg/ day of thalidomide, he developed dyspnea and fever, followed by a
      macropapular rash in the trunk. The dyspnea got worse and a CT scan revealed
      interstitial pneumonia 16 days after the treatment. He required mechanical
      ventilatory support. Bronchoalveolar lavage fluid revealed eosinophilia,
      suggesting a thalidomide-induced interstitial pneumonia. Thalidomide was
      discontinued and methylprednisolone (1000 mg/d x 3 days) was started, and the
      pneumonia and rash markedly improved within six days. After that the patient
      contracted MRSA pneumonia and died of MRSA septicemia.

PMID- 15510839
TI  - [Primary diffuse large B-cell lymphoma of the esophagus].
AB  - A 64-year-old man with primary esophageal lymphoma suffered from dysphagia. An
      upper gastrointestinal examination revealed a partly ulcerated submucosal tumor
      in the upper portion of the esophagus. Histopathological and immunohistological
      examination of endoscopic biopsy specimens showed diffuse large B-cell lymphoma
      of the immunoblastic type. Improvement of the dysphagia and esophageal findings
      were noted after chemotherapy and radiotherapy. A review of the literature
      indicated that primary esophageal lymphomas account for less than 1% of all
      gastrointestinal lymphomas, and less than 0.1% of all malignant lymphomas.
      Because of the rarity of primary esophageal lymphoma, its clinical and biological
      characteristics are not currently well known. It is important to accumulate
      information on, and to further investigate patients with, primary esophageal
      lymphoma.

PMID- 15510840
TI  - Preoperative mechanical bowel preparation unnecessary in patients undergoing
      thoracic surgery.
AB  - OBJECTIVE: The purpose of this study was to assess a hypothesis that routine
      mechanical bowel preparation (MBP) is unnecessary before thoracic surgery.
      METHODS: Five hundreds and sixty cases of standard thoracic surgery including
      unilateral thoracotomies, bilateral thoracotomies, median sternotomies and video
      assisted thoracic surgery have been performed in Kyushu Medical Center Hospital
      from June 1999 to December 2002. Two hundreds and eighty cases received
      preoperative MBP and the other 280 cases did not receive it. The usefulness of
      MBP was assessed retrospectively with these patients. RESULTS: It proved that
      cessation of MBP did not provide any disadvantage for postoperative complication
      and hospital stay. CONCLUSIONS: From these results, routine MBP appears to be
      unnecessary before thoracic surgery.

PMID- 15510841
TI  - Effect of delayed induction of postischemic hypothermia on spinal cord damage
      induced by transient ischemic insult in rabbits.
AB  - OBJECTIVE: This study was performed to determine the effect of delayed induction
      of mild hypothermia after transient spinal cord ischemia in rabbits. METHODS:
      Abdominal aortic occlusion was performed for 15 minutes to induce spinal cord
      ischemia at a rectal temperature of 37.3 +/- 0.3 degrees C. Four groups of
      rabbits were investigated: Group 1 (n = 8) was subjected to ischemia and
      reperfused at the same temperature for 7 hours; Group 2 (n = 8) was subjected to
      ischemia and reperfused at the same temperature for 1 hour, followed by 6 hours
      of systemic hypothermia (32.5 +/- 0.5 degrees C); Group 3 (n = 8) was subjected
      to ischemia, reperfusion at the same temperature for 3 hours and then 6 hours of
      systemic hypothermia (32.5 +/- 0.5 degrees C); and Group 4 (n = 8) comprised non
      ischemic controls. Neurological status of all rabbits in Groups 1-3 was recorded
      and animals were sacrificed 1 week after ischemic injury. Spinal cord sections
      were examined microscopically to determine the extent of ischemic neuronal
      damage. RESULTS: Mean modified Tarlov's score at 1 week after ischemic insult was
      0.5 +/- 0.8 in Group 1, compared to 43 +/- 1.5 in Group 2 and 2.9 +/- 1.8 in
      Group 3. Mean total number of surviving neurons within examined sections of
      spinal cord was significantly greater for Groups 2 and 3 compared with Group 1
      (Group 1, 81 +/- 66.1; Group 2, 293.4 +/- 110.9; Group 3, 227.1 +/- 105.5; p <
      0.001). CONCLUSIONS: Delayed postischemic hypothermia induced within 3 hours
      after reperfusion significantly reduces ischemia-induced spinal cord neuronal
      damage in rabbits.

PMID- 15510842
TI  - Omental transfer for mediastinitis in a patient with early gastric cancer.
AB  - We encountered a patient with mediastinitis after coronary artery bypass grafting
      and early gastric cancer requiring surgical resection. We treated the patient's
      mediastinitis by omental transfer since complete resection of the malignancy did
      not require omentectomy. However, in the procedure for harvesting an omental
      flap, lymph nodes along the gastroepiploic artery (GEA) were left in the stomach
      for dissection after recovery from mediastinitis; the greater omentum was divided
      along the outside of the GEA, and was used as a flap based on the left GEA. After
      mediastinitis was successfully treated, the patient underwent distal gastrectomy
      and resection of lymph nodes, including those along the GEA. Although indication
      for omental transfer must be carefully considered when selecting this procedure
      for mediastinitis patients with malignancies of the abdomen, this technique of
      harvesting the greater omentum was useful in the present case of a mediastinitis
      patient with surgical indications of early gastric cancer.

PMID- 15510844
TI  - Combined large cell neuroendocrine carcinoma.
AB  - We report a case of combined large cell neuroendocrine carcinoma. A 78-year-old
      man with vertigo was referred to our hospital where chest X-ray revealed a tumor
      shadow in the right lung. A transbronchial lung biopsy specimen verified a
      diagnosis of non-small cell lung carcinoma (cT1N0M0). Right lower lobectomy with
      mediastinal lymph node dissection (#7, 8, 9) was performed. A postoperative
      histological diagnosis was combined large cell neuroendocrine carcinoma of a
      component of squamous cell carcinoma [pT4 (pm) N2M0]. The patient received
      concurrent chemoradiotherapy due to upper mediastinal lymph node metastasis 4
      months after surgery. The chemoradiotherapy well responded and the patient
      remains well 9 months after surgery.

PMID- 15510843
TI  - Traumatic pericardial rupture involved with complication by blunt chest trauma.
AB  - A 65-year-old man who had sustained a blunt chest trauma in a traffic accident
      demonstrated a mass in the left hilum by chest radiography. Emergency surgery
      demonstrated a rupture of the left-side pericardium with herniation of the heart
      into the left pleural cavity along with a right ventricular rupture. The tear in
      the right ventricle was sutured using 4-0 polypropylene with felt and the
      pericardial rupture was repaired with an expanded polytetrafluoroethylene sheet.
      A 31-year-old man who had been crushed against a tree while skiing 5 years and 6
      months earlier was diagnosed as having severe tricuspid valve regurgitation and
      tricuspid valve replacement was performed. Large left pericardial defect was
      found and repaired with an equine pericardial patch. In both cases, a bridging of
      phrenic nerve was found in the pericardial defect that was regarded as a
      traumatic rupture.

PMID- 15510845
TI  - Mitral valve repair in a child with infectious endocarditis followed by
      meningitis.
AB  - A one-year-old boy without congenital cardiac anomaly suffered from meningitis
      and subsequent acute infective endocarditis that resulted in mitral
      regurgitation. During antibiotic therapy and management of congestive heart
      failure, he suddenly developed an acute subdural hematoma, and an aneurysm of the
      cerebral artery was detected by brain computed tomography. Clipping of the
      aneurysm was performed by neurosurgery, and 9 days after clipping, we performed
      mitral valve repair. Kay-Reed annuloplasty was performed and annulus size was
      reduced from 20 to 16 mm, and edge to edge repair of anterior and posterior
      leaflets near the commissure to reconstruct ruptured anterior leaflet chordae.
      This method is easy and useful to control mitral regurgitation when mitral
      chordae are detached from near commissure especially in child case.

PMID- 15510846
TI  - Another blood supply to Adamkiewicz's artery.
AB  - A 76-year-old man underwent endovascular stent-grafting therapy for chronic
      aortic dissection. The preoperative multi detector row helical computed
      tomography (CT) revealed that Adamkiewicz's artery originated from the level of
      thoracic 9 intercostal artery. Intraoperative monitoring of motor evoked
      potentials showed no reduction of amplitude in the anterior tibialis muscle after
      deployment retrievable stent-graft. Postoperative CT showed that stent-graft
      blocked the ostium of intercostal arteries including Adamkiewicz's artery. On the
      other hand, the distal portion of the Adamkiewicz's artery was clearly enhanced.
      Our result showed that there is a collateral network supplying to Adamkiewicz's
      artery.

PMID- 15510847
TI  - Intercostal hemangioma.
AB  - This paper presents a case of intercostal hemangioma, in which a complete
      surgical resection was accomplished based upon a tentative diagnosis provided by
      magnetic resonance imaging (MRI). A 27-year-old man visited our hospital for the
      evaluation of chest pain and shortness of breath after exertion. Computed
      tomography showed a soft tissue mass, 5.5 x 3.5 cm in size, arising from the
      right lateral 7th intercostal space. Dynamic MRI showed that the mass was
      enhanced rapidly in the early phase and that this early enhancement was
      maintained during the delayed phase, which was compatible with a diagnosis of
      intercostal hemangioma. The patient underwent surgery, and a complete resection
      of the tumor with the right 7th and 8th ribs and their intercostal muscles was
      accomplished. Histopathological examination confirmed the diagnosis of
      intramuscular hemangioma of the large-vessel type. Presently, 6 months after the
      operation, the patient is doing well, without any evidence of local recurrence.

PMID- 15510848
TI  - What does the public ask of the JATs? Results and feedback about insufficient
      public information distribution.
AB  - In order for the Japanese Association for Thoracic Surgery (JATS) to undertake
      appropriate internal reforms, civil receptiveness and sensitivity to the needs of
      the public are required. Although the JATS is conscious of the needs of
      physicians, the needs of the public has almost never been addressed. The JATS
      should place a priority on its mission to advance medicine, to contribute to the
      public welfare, to distribute information to the public, and to be publicly
      accountable over seeking the members' well-being. The web site of the "Lung
      Cancer Medical Treatment Network" (Haigan Chiryo Net), which was launched by one
      of us 5 years ago, is one example of information distribution. Visitors to the
      web site have gradually increased to more than 20,000 people per month, totaling
      753,000 visits. More than 1200 persons have requested second opinions by e-mail
      or facsimile. We propose that the nature and purpose of the JATS's civic
      activities be specified and that the JATS consider and establish methods for
      public information distribution. Using a web site is an effective method for
      these activities, but an opinion document about medical problems and the medical
      system of chest surgery should be created and distributed. The establishment of a
      consultation service for second opinions should also be considered.

PMID- 15510849
TI  - The effect of insufficiency of tetrahydrobiopterin on endothelial function and
      vasoactivity.

PMID- 15510850
TI  - Bonding durability between orthodontic brackets and human enamel treated with
      megabond self-etching primer using 4-META/MMA-TBB resin cement.
AB  - The purpose of this study was to determine the bonding durability when a Megabond
      self-etching primer is used with 4-META/MMA-TBB resin to bond metal orthodontic
      brackets to human premolar enamel. Three conditions of enamel were prepared:
      Megabond self-etching primer without saliva contamination, Megabond self-etching
      primer with saliva contamination, and repeat Megabond self-etching priming after
      saliva contamination. Shear bond strengths were measured after immersion in water
      at 37 degrees C for 24 hours, or after 2000 or 5000 cycles of thermal cycling
      between 5 degrees C and 55 degrees C. There were no significant differences in
      shear bond strength among the three groups not only before thermal cycling, but
      also after thermal cycling. FE-SEM observation revealed the presence of saliva
      and reduced amount of resin tag formation after saliva contamination. The present
      study provided the evidence in human teeth that when using 4-META/MMA-TBB resin,
      Megabond self-etching primer treatment produced tight bonding even when surface
      was contaminated with saliva.

PMID- 15510851
TI  - Osteoblast proliferation behavior and bone formation on and in CO3apatite
      collagen sponges with a porous hydroxyapatite frame.
AB  - To develop a new biodegradable scaffold biomaterial reinforced with a frame,
      synthesized CO3apatite (CO3Ap) was mixed with a neutralized collagen gel. Then, 0
      and 70% (w/w) CO3Ap-collagen mixtures (70% CO3Ap weight/mixture weight) were
      lyophilized into sponges in a HAp frame ring with 0.5-mm pores. SEM observation
      of CO3Ap-collagen sponges showed favorable pores for cells invasion. Mouse
      osteoblast MC3T3-E1 cells were cultured in alphaMEM with 10% FCS for 1, 10 and 20
      days. Matrix substances on the pure collagen sponge samples increased with the
      culture period such that the sponge surface was almost covered. A sectional view
      of hematoxylin-eosin staining confirmed that osteoblast cells had well invaded
      the CO3Ap-collagen sponge. When these sponge-frame complexes were implanted
      beneath the periosteum cranii of rats, newly created bone was observed to grow
      toward the inner core of the complex from the surface of the periosteum cranii.
      Based on these results, reinforced CO3Ap-collagen sponges are expected to be used
      as hard tissue scaffold biomaterials for therapeutic purposes.

PMID- 15510852
TI  - Durability of adhesion between 4-META/MMA-TBB resin and cementum.
AB  - 4-META/MMA-TBB resin has shown good biocompatibility and remarkable adhesion to
      dentin. It seems to be suitable for use in periodontal tissues for retrograde
      root sealing and treatment of vertically fractured roots. For an adhesive resin
      to be useful clinically, it must bond not only to the dentin but also to the
      cementum. The purpose of this study was to evaluate the long-term adhesion
      durability of 4-META/MMA-TBB resin to cementum kept in water at 37 degrees C.
      Bovine root cementum and dentin surfaces were treated with 10-3 solution before 4
      META/MMA-TBB resin was applied on treated surfaces. The micro-tensile bond
      strength (microTBS) decreased during the first two months; dye leakage value
      increased during the first four months and stabilized thereafter. No significant
      differences in adhesion durability were recognized between the dentin and
      cementum.

PMID- 15510853
TI  - Tensile bond strength of 4-META/MMA-TBB resin to ground bovine enamel using a
      self-etching primer.
AB  - The purpose of this study was to examine the effectiveness of self-etching primer
      in adhering 4-META/MMA-TBB resin to bovine enamel. In this study, we designed an
      original self-etching primer which contained an aqueous mixture of 4-MET, 35 wt%
      HEMA, and ferric chloride. The polished bovine enamel surface was treated with
      self-etching primer for 30 seconds. Tensile bond strength of 4-META/MMA-TBB resin
      to enamel was measured after 1-day immersion in water at 37 degrees C. The self
      etching primer containing 30 wt% 4-MET and 35 wt% HEMA (4MET30) gave a
      significantly higher bond strength of 11.2+/-2.8 MPa than other self-etching
      primers. The addition of ferric chloride into 4MET30 primer significantly
      decreased tensile bond strength. SEM observation revealed that 4MET30 treatment
      produced no distinct dissolution on enamel. When compared with phosphoric acid
      etching, the self-etching primer containing 30 wt% 4-MET and 35 wt% HEMA was more
      superior in adhering 4-META/MMA-TBB resin to enamel.

PMID- 15510854
TI  - Physical properties of different composites.
AB  - The purpose of this study was to determine the flexural strength (FS), flexural
      modulus (FM), depth of cure (DC), polymerization shrinkage (PS), and
      microhardness (VH) of the following composites: Two packable composites--Filtek P
      60 and Solitaire 2; One ion-releasing composite--riston AT; and Two hybrid
      composites--Charisma and Filtek Z-250. Data of the different tests conducted were
      obtained as follows: FS and FM data were determined with a universal-testing
      machine; Polymerization shrinkage was determined using the apparatus of Watts and
      Cash; Depth of cure was measured with a micrometer (Mitotuyo, UK); and
      Microhardness was measured with a Shimadzu Microhardness tester (500 g, 15
      seconds). All data of the different tests were statistically analyzed by one-way
      variance analysis (ANOVA), which yielded the following results: Filtek Z-250
      showed the statistically highest flexural strength and modulus values. Solitaire
      2 exhibited the highest shrinkage, while the volumetric shrinkage results of
      Filtek Z-250 and Filtek P-60 ranked the lowest. For depth of cure, there were no
      statistically significant differences among all materials tested (p<0.05).
      Microhardness results revealed the following tendency: Filtek Z-250 = Filtek P-60
      > Ariston AT = Solitaire 2 = Charisma.

PMID- 15510855
TI  - Application of the laser speckle-correlation method for determining the shrinkage
      vector of a light-cured resin.
AB  - The purpose of this study was to develop a method to monitor the free-shrinkage
      vectors of a light-cured resin using laser speckle contrast measurement. The
      laser speckle contrast measurement system comprised a semiconductor laser, a
      speckle analyzer, and a computer-controlled data acquisition system. A light
      cured resin was condensed into a glass tube and irradiated using a curing unit,
      the light intensity of which was adjusted to either 100 or 600 mW/cm2. The
      speckle patterns obtained from the lateral surface of the specimen were monitored
      using a CCD camera connected to a computer. The speckle images were analyzed
      using a phase-only correlation algorithm, and movements of the pattern were
      traced. The speckle pattern revealed rapid movement almost immediately after
      light exposure was initiated, and the orientation of free-shrinkage vectors is
      dependent on light intensity. When the specimens were irradiated at the lower
      light intensity, the free shrinkage vectors were oriented towards the light
      source. On the other hand, when irradiated at the higher light intensity, the
      free-shrinkage vectors of these specimens tended to orient towards the bottom
      surface. The effectiveness of the employed method to determine free-shrinkage
      vectors is thus proven through the results of this study.

PMID- 15510856
TI  - Light-curing reinforcement for denture base resin using a glass fiber cloth pre
      impregnated with various urethane oligomers.
AB  - The purpose of this study was to investigate the flexural properties of denture
      base resin reinforced using glass fiber cloth and a urethane oligomer. The five
      types of oligomer used in this study were S5, S9, S3, U4, and U6, which have
      varying functional groups and viscosities. The flexural properties of S9 with
      glass fiber cloth could not be measured because S9 is elastic. In the heat-cured
      resin reinforced with S9, the reinforcement peeled away from the resin. In the
      self- and light-cured resins reinforced with S9, the flexural properties
      increased significantly. When reinforced with the other four oligomers (S5, S3,
      U4, and U6), the flexural strength and flexural modulus of the self-, heat-, and
      light-cured resins increased significantly (p<0.01).

PMID- 15510857
TI  - Development of Al2O3 fiber-reinforced Al2O3-based ceramics.
AB  - The purpose of this study was to use a tape casting technique to develop an Al2O3
      fiber-reinforced Al2O3-based ceramic material (Al2O3-fiber/Al2O3 composite) into
      a new type of dental ceramic. The Al2O3-based ceramic used a matrix consisting of
      60 wt% Al2O3 powder and 40 wt% SiO2-B2O3 powder. The prepreg sheets of Al2O3
      fiber/Al2O3 composite (in which uniaxially aligned Al2O3 fibers were infiltrated
      with the Al2O3-based matrix) were fabricated continuously using tape casting
      technique with a doctor blade system. Multilayer preforms of Al2O3-fiber/Al2O3
      composite sheets were then sintered at a maximum temperature of 1000 degrees C
      under an atmospheric pressure in a furnace. The results showed that the shrinkage
      and bending properties of Al2O3-fiber/Al2O3 composite exceeded those of
      unreinforced Al2O3--hence demonstrating the positive effects of fiber
      reinforcement. In conclusion, the tape casting technique has been utilized to
      successfully develop a new type of dental ceramic material.

PMID- 15510858
TI  - Marginal gap formation and fluoride release of resin-modified glass-ionomer
      cement: effect of silanized spherical silica filler addition.
AB  - The purpose of this study was to investigate the effects of silanized spherical
      silica fillers (SF) on the immediate and 24-hour marginal gaps of resin-modified
      glass-ionomer cement (RMGIC) in tooth cavities. In correlation with marginal gap
      formation in the tooth cavity, these influencing factors were also examined:
      marginal gap and setting shrinkage of cement in the Teflon mold, as well as the
      shear bond strength to tooth substrate. Moreover in correlation with caries
      prevention, fluoride release was examined too. In this investigation, the fillers
      were mixed into the RMGIC powder (Fuji II LC EM). Untreated spherical silica
      filler (UF)-added RMGIC was used as a comparison. When compared with the control
      (i.e., original RMGIC), the addition of SF significantly decreased immediate
      marginal gap in tooth cavities and setting shrinkage in Teflon mold up to 63% and
      66% respectively. Fluoride release was significantly reduced too. Apart from
      these results, this study showed that addition of 5 wt% SF increased the shear
      bond strength to human enamel and dentin.

PMID- 15510859
TI  - Phosphate-bonded ZrSiO4 investments added with ZrC and ZrN for casting titanium.
AB  - In this study, new investments for titanium were developed by adding ZrC or ZrN
      as chemical additive for thermal expansion to a phosphate-bonded zircon (ZrSiO4)
      investment. The following effects were then examined: setting expansion, residual
      thermal expansion, and compressive strength of these experimental investments;
      surface roughness of cast plate; and casting accuracy of titanium crown. For
      residual thermal expansion, it occurred even while investments were cooled to
      room temperature after firing in air atmosphere. This was due to the additives'
      oxidation to ZrO2--suggesting that residual thermal expansion increased with
      increased amount of these additives. As for casting accuracy of full-crown cast
      into molds at room temperature, it correlated with the ZrN content. Hence by
      adding the right amount of ZrN, cast titanium crowns with low surface roughness
      and good adaptability could be obtained.

PMID- 15510860
TI  - An ultrastructural analysis of the prototype single-step adhesive applied on
      enamel and dentin surfaces.
AB  - A new type of self-etching agent, the single-step adhesive, was developed. The
      purpose of this study was to investigate the difference in the ultrastructural
      features of enamel and dentin surfaces following application of the prototype
      single-step adhesive (EXM618, 3M, MN, USA). Extracted caries-free human premolars
      were used in this study. Occlusal enamels of teeth--to be used as cut surface
      specimens--were removed perpendicular to the long axis of the specimens. The
      mesial and distal surfaces of these teeth, on the other hand, were used as uncut
      surface specimens in the test. In addition, Mega Bond (Kuraray Medical Inc.,
      Tokyo, Japan) and Xeno CFII Bond (Dentsply Sankin, Tokyo, Japan) were used as
      controls. After covering half of the tooth surfaces with nail varnish (for
      control), the other half of each surface was treated with one of the three test
      adhesives--EXM618, Mega Bond, or Xeno CFII Bond--according to the manufacturer's
      recommendations. Conditioned enamel and dentin surfaces (i.e., decalcified depth
      and rugged surface) were observed with a scanning confocal laser microscope (SCLM
      1100, Olympus, Tokyo, Japan; henceforth abbreviated as SCLM). Based on the
      findings of this study, the prototype single-step adhesive EXM618 appears to be
      suitable for use in dental clinics.

PMID- 15510861
TI  - Effects of added sodium alginate on mechanical strength of apatite cement.
AB  - Effects of added sodium alginate on the mechanical strength of Biopex, one type
      of apatite cement, were investigated since sodium alginate addition is very
      effective for Biopex to acquire anti-washout property. Addition of sodium
      alginate into the liquid phase of Biopex resulted in a slower transformation to
      apatitic monolith. As a result, mechanical strength of set Biopex in terms of
      diametral tensile strength (DTS) decreased when it was hardened in an incubator
      kept at 37 degrees C and 100% relative humidity for 7 days. However, DTS value
      increased with increase in the amount of added sodium alginate when the Biopex
      paste was immersed in 0.9% saline at 37 degrees C for 7 days. Set Biopex with
      less sodium alginate also showed larger porosity. Based on these findings, we
      concluded that added sodium alginate was effective in increasing the mechanical
      strength of Biopex by inhibiting liquid penetration into its paste when it is
      exposed to body fluids.

PMID- 15510862
TI  - The effects of initial hemostatic period on the mechanical strength and
      transformation of apatite cement.
AB  - It is well known that apatite cement causes inflammatory response if it is
      exposed to blood before setting. In this respect, the hemostatic procedure is
      very important. However, it has not been clarified how initial hemostasis affects
      the other basic properties of apatite cement. In the present study, the effect of
      initial hemostasis on the setting reaction was simulated by allowing the apatite
      cement paste to be hardened in an incubator for 1 to 30 minutes and then immersed
      in saline up to 7 days. We found faster transformation of apatite cement to
      apatitic mineral and higher mechanical strength of the set mass when the cement
      paste underwent a longer pre-hardening period. We also found that earlier
      exposure of apatite cement to saline resulted in a set mass with larger porosity.
      It is thought that the larger porosity of the cement is caused by the penetration
      of liquid into the cement paste, thus leading to lower mechanical strength and
      slower transformation of the apatite cement to apatitic mineral. We concluded,
      therefore, that hemostatic procedure is important not only to prevent
      inflammatory response but also to obtain a set mass with higher mechanical
      strength and faster transformation to apatitic mineral.

PMID- 15510863
TI  - Long-term effects of Ag-containing alloys on mucous tissue present in biopsy
      samples.
AB  - The aim of this study was to investigate the long-term effects of alloys
      containing silver (mainly Ag-Sn alloy) on oral mucous tissue. We observed biopsy
      tissue specimens from patients diagnosed as having amalgam tattoo and/or metal
      pigmentation by light and electron microscopy and electron-probe microanalysis
      (EPMA). In most cases, Ag-Sn alloy was present in the tissue but it could not be
      confirmed if the alloy originated from amalgam. Distributions of both Ag-S and Ag
      Sn have typical patterns. Most Ag forms Ag2S and is stably deposited in three
      patterns along the collagen, basement membrane, and fibrous cells without
      inducing any host reaction. On the other hand, Sn forms large granules that
      contain Ag, S, C, N, P, and Ca, and is in soft state in the tissue. Tissue
      reactions to the alloy become weaker as time passes.

PMID- 15510864
TI  - Dimensional accuracy of acrylic resin maxillary denture base polymerized by a new
      injection pressing method.
AB  - The purpose of this study was to confirm the dimensional accuracy of a newly
      developed injection pressing method for resin polymerization by making use of the
      internal electric resistance of resin to determine the optimal timing for resin
      injection. A new injection pressing polymerization pot with a built-in system to
      measure the internal electric resistance of resin was used for resin
      polymerization. Fluid-type resin was injected into the mold of a maxillary
      complete denture base under nine different conditions: three different timings
      for resin injection according to the electric resistance of resin dough (early
      stage: 11 Mohms; intermediate stage: 16 Mohms; final stage: 21 Mohms) and three
      different motor powers for resin injection (2000 N, 4000 N, and 6000 N). In the
      best polymerization condition (injected during the early stage of resin dough
      under a motor power of 6000 N), the adaptation of the denture base showed a
      statistically significant improvement compared with the conventional pouring
      method.

PMID- 15510865
TI  - Morphological and chemical characterizations of the interface of a hydroxyapatite
      coated implant.
AB  - The present study aimed at morphological and chemical characterization of the
      coating-substrate interface of a commercially available dental implant coated
      with plasma-sprayed hydroxyapatite (HA). For this purpose, elements in the
      chemically and mechanically exposed substrate surfaces were analyzed by EPMA and
      XPS. A thin titanium oxide film containing Ca and P was found at the interface.
      When the implant was subjected to mechanical stress, a mixed mode of cohesive and
      interfacial fractures occurred. The cohesive fracture was due to separation of
      the oxide film from the substrate, while the interfacial fracture was due to
      exfoliation of the coating from the oxide film bonded to the substrate. Analysis
      showed diffusion of Ca into the metal substrate, hence indicating the presence of
      chemical bond at the interface. However, mechanical interlocking seemed to play
      the major role in the interfacial bond.

PMID- 15510866
TI  - Determination of elastic modulus of the components at dentin-resin interface
      using the ultrasonic device.
AB  - The purpose of this study was to determine the elastic moduli of the components
      at resin-dentin interface with the use of an ultrasonic device. Dentin plates
      were obtained from freshly extracted bovine incisors with a shape in rectangular
      form. Resin composites and bonding agents were polymerized and trimmed in the
      same shape as the dentin specimens. The ultrasonic equipment employed in this
      study was comprised of a Pulser-Receiver, transducers, and an oscilloscope. Each
      elastic modulus was determined by measuring the longitudinal and shear wave sound
      velocities. The mean elastic modulus of mineralized dentin was 17.4 GPa, while
      that of demineralized dentin was 1.4 GPa. When the demineralized dentin was
      immersed in bonding agents, the elastic modulus changed to 3.7-4.7 GPa, and these
      values were significantly higher than those of demineralized dentin. A gradient
      in elastic modulus was detected as the analysis shifted from the dentin side to
      the resin composite.

PMID- 15510867
TI  - Color stability of acrylic resin adhesives with different initiation modes.
AB  - The purpose of this study was to evaluate the color stability of two acrylic
      resin adhesives with different activation systems: a benzoyl peroxide (BPO)-amine
      redox system and a tri-n-butylborane (TBB) derivative system. The colorimetric
      values of the two resins in different shades (Clear and Ivory) were determined
      (n=5) 24 hours after polymerization as a baseline using the L*a*b* system of the
      Commission Internationale de l'Eclairage (CIE). The specimens were thereafter
      immersed in distilled water, and the color difference (deltaE*) values were
      calculated. After 24 weeks, the TBB-initiated material showed a significantly
      (p<0.05) lower color change than the BPO-amine-initiated material. The deltaE*
      values for the BPO-amine-initiated materials were 6.9 for Clear and 15.8 for
      Ivory, whereas those for the TBB-initiated materials were 1.3 and 1.8
      respectively. Thus, it was concluded that the TBB-initiated material had superior
      color stability to that of the BPO-amine-initiated material.

PMID- 15510868
TI  - Gypsum-bonded investment and dental precision casting (IV) transformation of III
      CaSO4 to II-CaSO4.
AB  - The degree of III-CaSO4 to II-CaSO4 transition was estimated on wet specimens, 25
      mm in diameter and 50 mm high, prepared from a gypsum-bonded investment for quick
      casting. After 30 min from mixing the specimens were heated in a 700 degrees C
      furnace until a specimen temperature of 200 degrees C to 700 degrees C was
      reached. The estimation was made by measuring mass changes of the specimens
      before and after heating. The transition reached 39% at 350 degrees C. The same
      estimation method, when applied to a previous study, showed no transition to this
      temperature in dry specimens heated slowly (5 degrees C/min). The large
      difference in transition found between the wet and dry specimens was attributed
      to the formation of alpha- and beta-hemihydrate, respectively. At 350-450 degrees
      C, the transition was 3% and 48%, respectively. The pronounced latter transition,
      generally identified by differential thermal analysis of gypsum, appears as the
      major investment shrinkage demonstrating its dry dehydration process.

PMID- 15510869
TI  - Corrosion behavior and surface characterization of Ti-20Cr alloy in a solution
      containing fluoride.
AB  - The purpose of this study was to investigate the correlation between corrosion
      resistance and surface composition of an experimental Ti-20 mass% Cr casting
      alloy in a saline solution containing fluoride. The alloy had a greater
      resistance to corrosion in a fluoride-containing saline solution than did
      commercially pure titanium. However, with confirmed dissolution of titanium and
      chromium, it meant that the fluoride in the saline solution corroded the alloy
      slightly. X-ray photoelectron spectroscopy analysis revealed that the surface
      composition of the alloy consisted of titanium and chromium oxides containing
      hydroxide. The [Ti]/([Ti] + [Cr]) ratio in the surface oxide film decreased when
      immersed in fluoride-containing saline solution, that is, the surface oxide film
      became chromium-rich oxide. Therefore, the alloy obtained good corrosion
      resistance to fluoride due to formation of a chromium-rich oxide film.

PMID- 15510870
TI  - The thickness effects of titanium castings on the surface reaction layer.
AB  - In this study, wedge-shaped CP titanium castings and Ti-6Al-7Nb alloy castings
      were produced by three types of investment. The effects of the castings'
      thickness on surface reaction layer were investigated by measuring Vickers
      hardness, observing the microstructure, and analyzing the oxygen concentration.
      It was found that the thickness of the surface reaction layer was affected by the
      thickness of the wedge-shaped castings, and that the hardness value near the
      surface became lower toward the tip of the wedge-shaped CP titanium and Ti-6Al
      7Nb alloy castings. The surface reaction layer of the Ti-6Al-7Nb alloy castings
      was thinner than that of the CP titanium castings.

PMID- 15510871
TI  - Investigation of preferred viscosity of irreversible hydrocolloid on preliminary
      impression for edentulism.
AB  - This study aims to investigate the preferred viscosity of irreversible
      hydrocolloid used in the preliminary impression for edentulism. Thirteen
      modalities of irreversible hydrocolloid were prepared by changing the W/P ratio.
      Discrimination test for the preferred viscosity was performed on 11
      prosthodontists (10.4+/-5.3 years of prosthetic experience). The parameter of
      discrimination test (P%) was calculated as the ratio of the number of adequate
      tests to the total number of tests. The P% and apparent viscosity coefficient
      (eta a) values measured by rheometer demonstrated good correlation (Y = -35.8X2 +
      118.4X - 22.8, r=0.86, p<0.01). Prosthodontists could judge the preferred
      viscosity based on their clinical experiences. On the preliminary impression for
      edentulism, the preferred viscosity demonstrated in vitro using a polyurethane
      maxilla model was 1.21 x 10(3) Pa x s.

PMID- 15510872
TI  - Thermal properties of dental materials--cavity liner and pulp capping agent.
AB  - We studied the thermal properties of cavity liners that included calcium
      phosphate as inorganic filler, in contrast to the conventional pulp capping
      agents. Therefore, thermal diffusivity, specific heat capacity, and thermal
      conductivity were measured. In addition, thermal conductivity results were
      compared with those of restorative materials and human dentin to examine thermal
      insulation effects. The thermal conductivity of cavity liners ranged from 0.23 to
      0.28 W m(-1) K(-1), and that of pulp capping agents ranged from 0.44 to 0.48 W m(
      1) K(-1). Test results indicated that the thermal conductivity of cavity liner
      was lower than those of human dentin, pulp capping agent, cast alloy, and
      composite resin for restoration, hence suggesting that cavity liner has a good
      thermal insulation effect.

PMID- 15510873
TI  - In vitro evaluation of bond strength and surface roughness of a resin-paint
      material.
AB  - This study investigated the stability of a resin-paint material (Master Palette)-
      which was developed for chairside shade modification of composite restorations-
      by evaluating its bond strength to indirect resin composite and surface
      degradation. Bond strength was evaluated with four surface treatments including
      an application of methylene chloride, airborne particle abrasion with 50 microm
      aluminum oxide, and additional applications of bonding agents after air-abrasion.
      The surface roughness (Rz value) of both the resin-paint and indirect resin
      composite before and after thermo-cycling (4-60 degrees C, 50,000 cycles) was
      also evaluated. All data were statistically analyzed by two-way ANOVA and
      Boneferroni's test (p=0.05). It was found that bond strength was improved by
      bonding agent application (14.9+/-1.9 MPa to 18.6+/-2.2 MPa, p<0.0054) after
      thermo-cycling. As for surface roughness, its results after thermo-cycling (2.7+/
      0.2 microm, p<0.001) demonstrated that the resin-paint needed further
      improvements to maintain the original surface texture.

PMID- 15510874
TI  - Cytocompatibility and viscoelastic properties of phthalate ester-free tissue
      conditioners.
AB  - We prepared prototype phthalate ester-free tissue conditioners (PFT) from a
      powder of poly(ethyl methacrylate) and a mixture of several liquids, including di
      n-butyl sebacate, benzyl benzoate (BB), and ethanol. The estrogenic activities of
      the liquids in the PFT were measured by an E-screen assay. We also assessed the
      cytotoxicity of the prototype and commercial tissue conditioners against a living
      skin equivalent. Finally, the viscoelastic properties were determined by
      measuring the rubber hardness and initial flow, while the effect of the mixing
      liquid on the mechanical properties of a denture resin was assessed by three
      point bending test. PFT did not show any estrogenic activity and displayed a low
      or a similar level of cytotoxicity as the conventional materials. The
      viscoelastic properties and the effect of the mixing liquid on mechanical
      properties were influenced by the quantity of BB present in the mixing liquid.
      The prototype is therefore a reasonable PFT candidate.

PMID- 15510875
TI  - The influence of orifice sealing with various filling materials on coronal
      leakage.
AB  - The aim of this study was to evaluate the sealing ability of materials filled in
      the orifice after root canal treatment. A total of 100 root canal-treated teeth
      were divided into six experimental groups: 1, Protect Liner F (PL); 2, Panavia F
      (PF); 3, DC core-Light cured (DCL); 4, DC core-Chemically cured (DCC); 5, Super
      EBA (SE); 6, Ketac (KC). The materials were filled--to a depth of 4 mm--in the
      coronal part of the root canals, and evaluated for microleakage. The number of
      teeth that failed to stop dye penetration in the filled materials differed
      statistically between PL and DCL or SE or KC, PF and SE or KC, DCC and KC, DCL
      and KC. The mean distance of dye penetration differed significantly between PL
      and SE or DCC, PF and SE or DCC. Hence, these results indicated the advantageous
      sealing ability of adhesive and flowable materials.

PMID- 15510876
TI  - Bonding strength and durability of alkaline-treated titanium to veneering resin.
AB  - The shear bonding strengths of a veneering resin to polished, sandblasted, and
      retention bead-cast commercially pure titanium (cpTi) plates with and without
      alkaline treatment were measured before and after thermal cycling. The bonding
      strengths to polished cpTi with and without alkaline treatment decreased
      remarkably with thermal cycling (p<0.01). The bonding strength to sandblasted
      cpTi with alkaline treatment at 5,000 thermal cycles showed no significant
      differences from those before thermal cycling (p>0.05), and those at 20,000
      thermal cycles showed values which were quite small (p<0.01). On the other hand,
      there were no significant differences in the bonding strengths of veneering resin
      to retention bead-cast cpTi in all conditions (p>0.05). These results suggested
      that although alkaline treatment is a simple and effective surface modification
      technique for titanium improving adhesion to resin due to formation of tight-fine
      rutile particles, it does not provide sufficient bonding durability for long
      period restorations.

PMID- 15510877
TI  - Effects of dietary acids on surface microhardness of various tooth-colored
      restoratives.
AB  - The aim of this in vitro study was to investigate if surface microhardness of
      Fuji IX GP, Vitremer, Dyract AP, and Prodigy is influenced by conditioning in
      aqueous solutions of lactic, orthophosphoric, citric, and acetic acids against
      bidistilled water (which was used as control). The pH values of acids used in
      this study were representative of dietary acids. All specimens were stored in
      bidistilled water for one week and then conditioned in the respective test
      solutions for another week. Citric (p<0.05) and acetic acids reduced, while
      lactic and orthophosphoric acids (p<0.05) increased the microhardness of both
      Fuji IX GP and Vitremer. On the other hand, microhardness of both Dyract AP and
      Prodigy was significantly reduced by all acidic media (p<0.05). The observed
      differences in the surface microhardness of various tooth-colored restorative
      materials conditioned in several media varied not only with the pH but also the
      nature of the acidic solution, and with the composition of the evaluated
      material.

PMID- 15510878
TI  - NY's best not good enough. Despite being a leader in adverse-event reporting,
      audit reveals some shortcomings, need for reform in N.Y.'s tracking system.
AB  - A New York audit of its well-regarded tracking system for adverse-event reporting
      drew fire when it revealed some problems with oversight. But state health
      officials defend the system, which is a model for other states. New Jersey
      official Marilyn Dahl, left, says New York has "been considered a national
      leader.

PMID- 15510879
TI  - Hot spot. Miami system vows to overhaul compliance office.

PMID- 15510880
TI  - The hidden debate topic. Rising healthcare costs threaten the best-laid plans to
      expand access to care.

PMID- 15510881
TI  - Building a bridge to mutual survival. Why hospitals must actively involve
      physicians in strategic decision-making.

PMID- 15510882
TI  - More docs say super-size it. Medical group mergers pose complex challenges but
      bring strength in numbers, deliver added patient convenience.

PMID- 15510883
TI  - A career he didn't count on. Michigan Professor Fries developed key assessment,
      reimbursement tools for the long-term-care sector. Interview by Joseph Mantone.

PMID- 15510884
TI  - [Genes and cardiovascular diseases].
AB  - In recent years there has been observed a relatively fast progress of explaining
      genetic mechanisms of development of many cardiovascular system diseases, mainly
      diseases conditioned by the mutation of single genes. The situation is different
      when analyzing the dependencies of complex cardiovascular system diseases whose
      development has many stages depending on exogenous or hereditary factors. The
      development of those diseases is due to interactions between particular
      environmental factors, individual differences in response to environmental
      factors and often complex genetic relations. The complexity of etiopathogenesis
      and clinical differentiation are the result of superposition of the effects of
      the action of single genes responsible for the development, predisposing and/or
      modulating the course. The analysis of genetic causes of cardiovascular system
      diseases is made on the basis of models and multigene polymorphisms.

PMID- 15510885
TI  - [Presence of Chlamydia pneumoniae in the carotid artery].
AB  - There is growing experimental evidence that Chlamydia pneumoniae is a risk factor
      and contribute to the development of atherosclerosis of carotid artery. This
      process might cause stenosis of carotid artery and TIA or stroke. AIM: Aim of
      this study was to evaluate the frequency of Ch. pneumoniae infection in carotid
      artery stenosis patients and in control group-healthy artery from multiorgan
      donors. MATERIAL AND METHODS: From each of 84 patients undergoing carotid
      endarterectomy the samples were analyzed by nested PCR for Ch. pneumoniae DNA.
      Furthermore we determined DNA Ch. pneumoniae in carotid artery from 20 multiorgan
      donors. RESULTS: In control group-healthy artery the PCR for Ch. pneumoniae was
      negative in all samples. Ch. pneumoniae was detected in 57 patients (67.85%) with
      symptomatic carotid artery stenosis, however in 27 patients (32.15%) the PCR test
      was negative. CONCLUSIONS: We did not observe infection of Ch. pneumoniae in
      healthy carotid artery-control group. We noted great frequency of infection in
      patients with stenosis of carotid artery. Patients with stenosis of carotid
      artery can be candidates to antibiotic therapy, which can slow down the
      progression of artery stenosis.

PMID- 15510886
TI  - [Effectiveness of extrameningeally administered opioids in patients with aortic
      prosthesis].
AB  - The examination was carried out in 60 men at the age of 56 to 78 (mean age 65.3
      years) treated by suturing of vascular prosthesis due to aneurysm of abdominal
      part of aorta, in which postoperative analgesia was done with the use of
      bupivacaine with opioids administered extradurally. Patients were divided into
      two groups consisting of 30 individuals each. In group I, patients were given
      0.25% bupivacaine with phentanyl, while in group II--bupivacaine appropriate for
      the need of the patient. Postoperative analgesia, in particular stages was
      complete in 75% of patients of group II and 63% of group I at twenty-four hour
      long maintenance of the initial dose of analgesics. Twenty-four hour long dose of
      bupivacaine to 210+/-20.5 mg in group I and 145+/-11.5 mg, while morphine 5.1+/
      1.2 mg. Fluctuation of the chosen haemodynamic and gasometric parameters were of
      no clinical importance. 7 patients suffered from nausea and vomiting, these
      patients included 2 patients from group I and in 5 patients from group II. On
      this basis of results, one may confirm that both methods of analgesia are equally
      effective, although it was possible to reduce the twenty-four hour long dose of
      bupivacaine, thus limiting the risk of depressive effect on heart muscle.

PMID- 15510887
TI  - [Incidence of factor VII and C3 in vascular anastomosis].
AB  - In order to study pathogenesis of vascular prosthesis healing process the
      following experiment was designed. 16 dogs underwent implantation of unilateral
      straight aorto-femoral teflon (PTFE, polytetrafluoroethylene) by-pass. After 6
      months all dogs were killed, dissected and vascular prostheses with margin of
      adjacent aorta and femoral artery were collected for further study. Areas of
      proximal and distal anastomosis were examined immunohistochemically. Presence of
      coagulation factor VII, and C3 complement factor were studied. The obtained
      results were analyzed statistically by means of t-Student test. Factor VII as
      well C3 were found in areas of both proximal and distal anastomosis.
      Concentration of all two substances in proximal and distal anastomosis was
      compared. No statistically valid differences in factor VII concentration in
      proximal and distal anastomosis were found, whereas amounts of C3 factor as well
      as degree of extracellular matrix infiltration were markedly higher in distal
      anastomosis.

PMID- 15510888
TI  - [Parameters of lipid peroxidation and low density lipoprotein (LDL) oxidation in
      the course of hyperthyroidism].
AB  - The aim of this study was to evaluate the influence of hyperthyroidism on lipid
      peroxidation and oxidative modification of low density lipoprotein (LDL). Twenty
      patients with hyperthyroidism due to Graves' disease or toxic multinodular goitre
      and 17 healthy subjects as the control group were investigated. Lipid
      peroxidation was measured by the serum level of malondialdehyde and 4
      hydroxynonenal (MDA+4-HNE) whereas the oxidative modification of LDL was
      determined by measuring the serum levels of antibodies against oxidized LDL (anti
      oxLDL). Ratios, which were evaluated as proportions of lipid peroxidation
      products level or anti-oxLDL level to the LDL-cholesterol level (LDL-C) were also
      determined: MDA+4-HNE/LDL-C and anti-oxLDL/LDL-C. The patients with
      hyperthyroidism displayed a significant elevation of the MDA+4-HNE/LDL-C ratio.
      The level of anti-oxLDL and anti-oxLD/LDL-C ratio were positively correlated with
      FT4 level and inversely correlated with HDL-cholesterol. These data suggest that
      the intensification of lipid peroxidation and oxidative modification of plasma
      lipoprotein is affected by changes in the level of thyroid hormones.

PMID- 15510889
TI  - [Prevalence of gastroesophageal reflux disease in patients with bronchial
      asthma].
AB  - The aim of this study was to determine the prevalence of gastroesophageal reflux
      disease (GERD) in patient with asthma, its relation to the severity of asthma,
      BMI (body mass index) and method of treatment. Two hundred eight patients with
      asthma were included in the study. All patients were carefully studied for asthma
      severity and surveyed using questionnaire specific for diagnosis of GERD also BMI
      was determined. Among the asthmatics 22.1% had chronic severe asthma, 43.3% had
      chronic moderate asthma and 34.6% had chronic mild asthma. GERD was present in
      86.9% of patients with severe asthma (p<0.001 as compared to moderate and mild
      asthma), 62.2% of patients with moderate asthma and 48.6% of patients with mild
      asthma. BMI was significantly higher in patients with severe asthma and reached
      28+/-5.3 kg/m2. GERD was present in all patients with severe asthma and BMI above
      30 kg/m2. 72.5%, 17.85% and 8.6% of patients with severe, moderate and mild
      asthma respectively, experienced symptoms of GERD after ingestion of theophylline
      and oral steroids. The study demonstrated a greater prevalence of GERD symptoms
      in severe asthma and related GERD to BMI and treatment with theophylline and
      systemic steroids.

PMID- 15510890
TI  - [Effect of arachidonic acid peroxidation products on the development of
      gastroesophageal reflux disease].
AB  - Oxygen free radicals trigger arachidonic acid peroxidation. The end-products of
      this reaction are malonyl dialdehyde (MDA) and conjugated dienes (CDs). The
      pattern of changes of MDA and CD concentrations in serum and esophagus mucosa
      homogenates were estimated in patients with GERD. The study was conducted on a
      group of 92 patients. They were divided into a non-esophagitis and co-existent
      esophagitis subgroup. The presence of inflammation was confirmed by means of
      pathomorphological examination. Results were verified against upper
      gastrointestinal tract endoscopy outcomes. The measurements were taken before and
      8 weeks after anti-GERD treatment. Results were compared against 20 patients
      awaiting hernia repair. In both groups MDA serum concentrations before treatment
      were significantly different from the control group (2.02 nmol/mL in group I and
      3.92 nmol/mL in group II). It decreased significantly after treatment in group II
      (2.72 nmol/mL) and insignificantly in group I. Also DS serum concentrations
      before treatment was significantly different comparing to the control group (1.34
      nmol/mL in group I, and 2.13 nmol/mL in group II). Like MDA, dienes'
      concentrations decreased significantly after treatment in group II and
      insignificantly in group I. MDA and DS tissue concentrations were always higher
      than the serum ones. Both before and after treatment they displayed statistically
      significant differences between the esophagitis and non-esophagitis groups.
      Oxygen free radicals measured by means of MDA and DS serum and tissue homogenate
      concentrations rise significantly in patients with GERD compared to the control
      group. Arachidonic acid peroxidation products' concentrations were significantly
      higher in patients with GERD and esophagitis than in the non-esophagitis group.

PMID- 15510891
TI  - [Frequency of sleep apnea syndrome in patients with acute stroke].
AB  - AIM: The association between sleep apnea syndrome (SAS) and cerebrovascular
      diseases although widely investigated in last years remains still unclear. The
      aim of our study was to determine the frequency of SAS in patients with stroke
      admitted to our stroke unit. MATERIAL AND METHODS: The examined group consisted
      of 27 patients with stroke confirmed by computed tomography (mean age: 66+/-10
      years, mean BMI: 24.4+/-4.4). In all cases a sleep study was performed in the
      acute phase of stroke (1-10 days) using a portable respiratory recording device
      (Poly Mesam) which measures nasal and oral air flow, chest wall movements, heart
      rate, oxygen saturation and snoring. RESULTS: The frequency of SAS
      (apnea/hypopnea index--AHI > or = 10/h) among patients in acute phase of stroke
      in our unit was 59% (15 persons). Mean AHI in SAS patients was 25.8+/-4.94. We
      observed mostly obstructive (53.3% of all) and mixed apneas (40%). Central apneas
      constituted only 6.6% of all recorded respiratory disorders. We did not observe
      any relationship between SAS and stroke localization. CONCLUSION: The frequency
      of SAS is high in patients with stroke. Screening for respiratory disorders
      during sleep should be a routine practice because it could help in decreasing
      stroke mortality.

PMID- 15510892
TI  - [Acute, stroke or thunderclap headache?].
AB  - Sudden, acute headache occurring for the first time in life may represent
      subarachnoid or perimesencephalic haemorrhage but it can also occur in the
      absence of pathologic conditions. This headache is widely named as "thunderclap"
      (TCH) or "stroke headache". Pathogenesis, diagnostic evaluation and headache
      characteristics is presented basing on retrospective evaluation of such patients
      admitted to Neurological Department between 1990-2002 with symptoms of TCH. The
      diagnosis of idiopathic TCH was established in 74 (21%) of 368 patients. No
      clinically significant difference between clinical manifestation of idiopathic
      and symptomatic TCH was observed. The most common concomitant diseases in
      idiopathic TCH patients were acute or chronic infections and hypertension. 40% of
      those patients had elevated inflammatory markers which normalised during
      hospitalisation in 20% of cases. We observed seasonal incidence with the highest
      incidence in summer and winter. 20% of patients presented to Neurological Dept
      with TCH consist of idiopathic, benign condition of unknown aetiology. Observed
      seasonal incidence with coexisting signs of infection may suggest the role of
      inflammatory process in benign TCH pathogenesis.

PMID- 15510893
TI  - [Resistance to antibiotics used in Helicobacter pylori infection in children].
AB  - In literature and clinical findings, the attention has been turned to the
      resistance to the antibiotics used in Helicobacter pylori eradication, especially
      metronidazole and clarithromycin. Drug-resistance was evaluated in 50 children.
      Primary drug-resistance to the antibiotics used in eradications was determined in
      this group, and additionally, in 18 children who were subjected twice to
      unsuccessful eradicative therapy. The highest secondary resistance to
      metronidazole up to 72.0% was found among conventionally used antibiotics.
      Primary resistance of H. pylori rods to clarithromycin was also high and equaled
      25.0%. However, in our study secondary resistance to macrolides was about 66.0%.
      In our study combined primary resistance to clarithromycin and metronidazole was
      about 7.2%. There was not H. pylori rods resistance to amoxicillin and
      tetracyclines.

PMID- 15510894
TI  - [Evaluation of neutrophils adhesive molecules CD11b/CD18 in the course of
      photochemotherapy (PUVA) for psoriasis vulgaris].
AB  - Psoriasis is a common, chronic dermatological disorder. Inflammatory cells
      assemble in epidermis in the early stage of acute psoriasis. Accumulation of
      neutrophils at the site of inflammation depends on the expression of adhesion
      molecules. A variety of stimuli--mediators or selectins can active CD11b/CD18
      molecules on the neutrophils surface. The aim of our study was expression of
      CD11b/CD18 molecules without and after stimulation by fMLP (formyl-Met-Leu-Phe)
      in patients with psoriasis vulgaris treated by PUVA. Expression of beta2
      integrins was estimated with MFI (mean fluorescence intensity). Neutrophils in
      patient with acute psoriasis showed an increase in CD11b/CD18 expression. It
      means about an activation of neutrophils and particular role of those molecules
      in granulocyte adhesion to epidermis in psoriasis.

PMID- 15510895
TI  - [Early results of rehabilitation after repair of the anterior cruciate ligament
      with open surgical or arthroscopic method].
AB  - The purpose of the study was to evaluate the methods of rehabilitation in
      patients who had undergone a plastic procedure (open or arthroscopic surgery) of
      the anterior cruciate ligament (ACL). The value of objective measurement methods
      used for monitoring the rehabilitation process was also assessed, with particular
      attention to the usefulness of goniometric pendulum test. All patients underwent
      rehabilitation in the Department of Motor Organ Rehabilitation at the Upper
      Silesian Rehabilitation Center in Ustron. For the purpose of the rehabilitation
      process evaluation, the condition of patients: goniometry and the pendulum test
      were performed twice, i.e. at admission and then at termination of
      rehabilitation. A modification of the Lysholm Scale and a subjective knee
      questionnaire (WAS) were also used. In group of healthy subjects only the
      pendulum test was done. Based on the obtained results it was found that the
      convalescence period needed to achieve the best ultimate capability within the
      knee joint mainly depended on the operative technique. However, appropriate
      kinesitherapy may affect the rate of convalescence in the group of patients with
      less favorable surgical outcome. In patients who had undergone a reconstruction
      of the anterior cruciate ligament, goniometric pendulum test is an effective tool
      to aid the evaluation of rehabilitation results; the test adds to the assessment
      done by the well-known subjective methods.

PMID- 15510896
TI  - [The HBeAg/antiHBe seroconversion as a result of lamivudine treatment in children
      with chronic hepatitis B unresponsive to previous interferon alpha therapy].
AB  - The aim of the study was evaluation the HBeAg/antiHBe seroconversion frequency as
      a result of lamivudine treatment in children who are nonresponders to previous
      IFN-alpha therapy. MATERIAL AND METHODS: The observation was carried out on 41
      children, aged 4-17 years, with biopsy-proven chronic hepatitis B (HBeAg+)
      treated with lamivudine 3-4 mg/kg/d (max. 100 mg/d) for 12 months. RESULTS: After
      6 months of lamivudine therapy 59.3% children normalized GPT activity and only 1
      child (2.5%) lost HBeAg. At the end of 12 months of therapy 81.5% normalized GPT
      activity and 4 of them (10%) lost HBeAg and seroconverted to antiHBe. None of
      treated children lost HBsAg. The age, sex, pretreatment GPT activity and active
      histological disease were not predictors of lamivudine-induced HBeAg loss. There
      were no side effects of lamivudine therapy except one boy who had severe
      thrombocytopenia. CONCLUSIONS: The HBeAg/antiHBe seroconversion rate after one
      year trial of lamivudine in children with chronic hepatitis B unresponsive to
      previous IFN alpha therapy was 10%. The age, sex, pretreatment GPT activity and
      active histologic disease were not predictors of lamivudine-induced HBeAg loss.

PMID- 15510898
TI  - [Hereditary prostate cancer].
AB  - About 10% of the prostate cancer cases were recognized as familial or hereditary.
      Till now gene/genes responsible for hereditary prostate cancer are not
      identified. Hereditary prostate cancer case concerning 3 brothers in family of 6
      siblings from first marriage and a grandson from second marriage was presented.
      Two brothers were treated radical prostatectomy because of confined disease. The
      third brother with spreading disease died after androgen blockade management. We
      did not find any linkage between chosen markers of PCaP region (Predisposing for
      Prostate Cancer) and prostate cancer occurrence in this family.

PMID- 15510897
TI  - [Evaluation of the usefulness and effectiveness of anxiolytic therapies in
      neoplastic diseases].
AB  - Anxiety accompanies patients at all stages of severe somatic diseases as well in
      the course of diagnostic procedures. It affects significantly quality of life of
      these patients and their relations with their physicians. It may also induce or
      exacerbate wide range of somatic complaints. OBJECTIVE: Evaluation of usefulness
      of anxiolytic therapies in patients with diagnosed neoplastic diseases.
      Comparison of anti-anxiety and antidepressant effects of alprazolam and diazepam
      in patients treated with systemic chemotherapy. MATERIAL AND METHODS: Final
      analysis included 45 patients with various malignancies randomly assigned to
      receive alprazolam 3 x 0.5 mg or diazepam 3 x 2 mg. Anti-anxiety effects of both
      drugs was evaluated four times during the 21-day follow-up period at one week
      intervals with help of Clinical Global Impression scale (CGI), Hamilton Anxiety
      Rating Scale (HARS), Hospital Anxiety and Depression Scale (HADS). Analysis of
      these questionnaires was performed with Mann-Whitney test and Wilcoxon test.
      RESULTS: Statistically significant reduction of anxiety was found in both study
      groups. Alprazolam was proven to be significantly more effective than diazepam in
      reduction of anxiety (HARS, HADS) and depressive symptoms accompanying anxiety
      (HADS). Alprazolam vs. diazepam showed better tolerance by patients. CONCLUSIONS:
      Alprazolam effectively reduced anxiety in patients suffering from malignant
      diseases. Alprazolam was found to reduce depressive symptoms in patients with
      neurotic disorders whereas no effects of this kind were observed for diazepam.

PMID- 15510899
TI  - [Darier disease type 1].
AB  - Darier disease (follicular dyskeratosis) is a rare genodermatosis determined by
      an autosomal dominant gene with variable penetration, characterized by a
      symmetrical eruption of hyperkeratotic papules with predilection to the
      seborrheic areas of the body. Unilateral, focal form is the one of the rare type
      of the Darier disease. Two clinical and genetical phenotypes of the segmental
      Darier disease have been recently reported: type 1--in which the skin outside of
      the localized manifestation is normal and type 2--showing a segmental affection
      in combination with diffuse skin involvement. The patient with type 1 segmental
      Darier disease is presented because of rare occurrence, diagnostic and
      therapeutic difficulties as well. The first keratotic papules on the left side of
      his trunk appeared at the age 14. The correct diagnosis based on clinical and
      histological picture has been established 38 years latter.

PMID- 15510900
TI  - [Clinical applications of recombinant complement inhibitors].
AB  - The complement system constitutes an important part of the innate immune system.
      Complement activation leads to the generation of C3a, C4a and C5a anaphylatoxins
      and the membrane attack complex. The anaphylatoxins mediate multiple reactions in
      the acute inflammatory response. Membrane attack complex inserts molecules into
      target membranes and causes cell lysis. The complement system can not
      discriminate between self and non-self cells and the inappropriate complement
      activation may lead to host cell damage. This destructive activity is tightly
      regulated by family of structurally and functionally related soluble and membrane
      bound proteins, which act as inhibitors of complement system. The inappropriate
      complement activation plays an essential role in the pathogenesis of many
      diseases. In the therapy of these diseases specific recombinant complement
      inhibitors can be used. Recombinant complement inhibitors can be produced in
      large amounts by different eukaryotic or prokaryotic systems. The choice of the
      system depends on kind of the post-translational modifications of proteins.

PMID- 15510901
TI  - [Radionuclide cisternography in the diagnosis of normal pressure hydrocephalus].
AB  - An overview of significant research results of the last four decades as well as
      the author's own experience have served as a basis for the presentation of the
      radioisotope method and the radiopharmaceuticals in the diagnostics of normal
      pressure hydrocephalus (NPH). Also the physiology of the formation of PM-R its
      flow and absorption have shortly been discussed. Hydrocephalus is a major
      clinical, diagnostic and therapeutical problem. In the initial diagnosis of that
      pathology, methods like CT and MRI play an important role, which has also been
      the subject of this article. A clear and useful classification of hydrocephalus
      has been presented as well as NPH in adults as a clinical pathological syndrome
      together with its etiology, diagnostics and the differentiation in relation to
      other forms of hydrocephalus. Hydrocephalus and the atrophy of the brain have
      been illustrated by images taken by the author. In the assessment of the NPH in
      terms of a patient's qualification for a shunting operation a number of
      diagnostic factors are of particular importance. These are: the infusion test
      using PM-R pressure measurement of the ventricle system or the subarachnoid space
      on the spinal cord level, the neuropsychological evaluation as well as the brain
      imaging using emission tomography SPECT or the measuring of the brain metabolism
      by PET technique. None of these methods has been universal in diagnostic terms.
      Radionuclide cisternography seems to be the most physiological method that allows
      to gain more direct insight into the dynamics and the PM-R flow and its
      absorption. The results of the radioisotope examination turn out to be the most
      reliable criterion in the diagnostics of NPH.

PMID- 15510902
TI  - [Sialic acid as a new marker of excessive alcohol consumption].
AB  - Alcoholism is one of the most frequent addictions among people. The early
      identification of alcohol abuse could increase the possibility of a favorable
      treatment outcome and reduce health care costs. Many biochemical laboratory
      markers of alcohol abuse have been used for several years, but each of them has
      clinical limitations. Recently, sialic acid (SA) has been suggested as a new
      potential marker of excessive alcohol consumption. In this paper, the general
      characteristic of SA has been given including the usefulness in the identifying
      of alcohol abuse. The clinical studies showed that serum and saliva sialic acid
      concentration was significantly higher in female and male alcoholics compared to
      social drinkers. It has been established also, that the serum SA level in male
      alcoholics was significantly increased after a short period of relapse to heavy
      alcohol drinking. In addition, the serum SA level was significantly decreased
      during an alcoholism treatment and abstinence. Sialic acid seems to be
      interesting biochemical marker of alcohol abuse (detecting, monitoring) with the
      diagnostic efficiency as good as, or even better, than the traditional markers
      used today.

PMID- 15510903
TI  - [Eosinophilic fasciitis--current database].
AB  - For the first time eosinophilic fasciitis (EF) was described by Shulman. It
      occurs predominantly in young men, rarely in older women and sporadically in
      children. The illness was characterised by swelling of the extremities, skin
      changes, myalgia, and elevation of the peripheral blood eosinophils count and
      hypergammaglobulinemia. It is followed by rapidly progressive cutaneous and
      subcutaneous indurations. The histopathologic examination of affected skin shows
      thickening of the fascia, deep dermal fibrosis and infiltration mainly consists
      of lymphocytes, plasmocytes, eosinophils. It is suggested that the cells from
      infiltration induce fibrosis. The tryptophan disturbance has significant
      influence on development of EF in predisposed persons. Eosinophilic fasciitis is
      classified into wide spectrum of scleroderma disorders by many authors. The
      authors tried to show differences between EF, morphea and systemic scleroderma.

PMID- 15510904
TI  - [Tuberous sclerosis--symptoms, diagnosis and treatment].
AB  - Tuberous sclerosis (Bourneville-Pringle disease) is an inherited disease with a
      prevalence rate ranging from 1:10,000 to 1:23,000. It is inherited as an
      autosomal dominant with a variable gene penetrance. However about 60% of cases
      represent new mutations. This disease is characterized by a defect in cell
      migration, proliferation and differentiation in organs like skin, brain, kidneys,
      heart, lungs and eyes. The mechanism involves formation of hamartoma tumours
      responsible for the functional impairment of these organs.

PMID- 15510905
TI  - [Neurological disorders after carbon monoxide intoxication].
AB  - Carbon monoxide (CO) intoxications still remain an important clinical problem.
      Under an influence of CO the cellular respiration is inhibited. Structures of the
      central nervous system (CNS), extremely vulnerable to hypoxia, are usually
      considerably damaged. In result, a variety of pathologic neurological symptoms
      may appear and characteristic biphasic course of complaints is often observed.
      The modern methods of neuroimaging (CT, MRI, SPECT, PET) enable to show a
      connection between found structural injury and clinical symptoms, and when
      repeatedly performed allow us to evaluate the dynamics of the CNS dysfunction.
      Because of late complications, which may occur after the period of latency, the
      authors stress the value of the prolonged (for up to few years) ambulatory
      observation of subjects after CO intoxication.

PMID- 15510906
TI  - [Heat shock proteins in colorectal carcinoma].
AB  - Heat-shock proteins (HSP) are a group of proteins, whose production in induced as
      a intracellular response to different kinds of stresses. They are also included
      in the group of chaperones, which are involved in protein folding and repairing
      of denatured proteins in the cells. Because of the protective role of HSP on the
      cellular level, many studies are focused on the role of heat shock proteins in
      anti-carcinogenic effect. The present study is a review of the literature
      regarding the value of HSP in the carcinogenic process.

PMID- 15510907
TI  - [Clinical assessment of major artery vasomotor endothelial function: methodology
      and importance for evaluating aging as a cardiovascular risk factor].
AB  - AGING AS A CARDIOVASCULAR RISK FACTOR: Atherosclerosis is the major cause of
      mortality in the Western world (>50%) as well as in Serbia and Montenegro (>60%).
      Atherosclerosis/arteriosclerosis functional and structural vascular changes as a
      consequence of angina pectoris, myocardial infarction, transient ischemic
      cerebrovascular attacks, stroke, ischaemic attacks in peripheral circulation
      and/or thromboembolic complications. Aging, lipids (oxidized LDL), infective
      agents, inflammation, increased glucose level, hypertension, smoking, increased
      homocysteine level, oxidative stress etc. are recognized as factors which lead to
      endothelial dysfunction and cause atherosclerosis. Thus, in response to such
      attacks endothelium releases different substances like: nitric oxide,
      prostacyclin, endothelium-derived hyperpolarizing factor (EDHF), endothelin,
      bradykinin, angiotensin II, free oxygen radicals etc. which could be involved in
      the pathogenesis of atherosclerosis. Atherosclerosis/arteriosclerosis begins with
      endothelial vasomotor and anti-thrombotic dysfunction and it is of strategic
      importance to discover this condition earlier. In regard aging, both higher
      thickness and stiffness of arterial blood vessels appear following an incidence
      of cardiovascular diseases. DIAGNOSTIC METHODS: Over the last decade non
      invasive, echosonographic method for visualization of carotid intima-media
      thickness (indicator of arteriosclerosis/atherosclerosis) was introduced in
      clinical practice. However, it is also used to compare brachial artery diameter
      changes, linear velocity and bloodflow which are estimated during basal
      conditions, during ischemia, during reactive hyperemia (endothelium/independent
      phase) as well as with left ventricular mass index. DISCUSSION AND CONCLUSION:
      Due to aging there is a decreased response to reactive hyperemia, increased
      carotid intima-media thickness and increased left ventricular mass, but there is
      a lack of time-dependent correlation. First endothelial dysfunction occur twenty
      years before any manifestations appear--as typical vascular and ventricular
      remodeling. During this period certain markers, for example homocysteine, and
      diagnostic procedures are important parts of primary prevention.

PMID- 15510908
TI  - [Nitric oxide and lung diseases].
AB  - INTRODUCTION: All three isoforms of nitric oxide synthase (NOS) are identified
      within various tissues of the respiratory system. ISOFORMS OF NOS: Under
      physiological conditions, small amounts of NO, produced by constitutive isoforms
      of NOS, appear to be important in regulation of basal pulmonary vascular tone and
      in mediating transition from fetal to neonatal circulation; also, NO exerts
      antiinflammatory actions, and modulates the respiratory smooth muscle tone. NO
      AND RESPIRATORY TRACT DISEASES: Under pathological conditions, inducible NOS
      derived NO may produce lung damage. In addition, increased or decreased
      production of NO is found in chronic obstructive pulmonary disease, cystic
      fibrosis, asthma and related inflammatory disorders, and exhaled NO level
      measurement is a useful tool in diagnostics of respiratory disorders. CONCLUSION:
      It has been shown that NO modulates contractility of the isolated diaphragm, and
      there are important interactions between NOS inhibitors and drugs for respiratory
      disorders (e.g. aminophylline).

PMID- 15510909
TI  - [Alpha-linolenic acid and cardiovascular diseases].
AB  - IMPORTANCE AND METABOLISM OF ALPHA-LINOLENIC ACID: Alpha-linolenic acid is an
      essential fatty acid which cannot be produced in the body and must be taken by
      food. Both in animals and humans, alpha-linolenic acid is desaturated and
      elongated into eicosapentaenoic and docosahexaenoic acid. It is also incorporated
      into plasma and tissue lipids and its conversion is affected by levels of
      linoleic acid. POTENTIAL ROLE IN PATHOGENESIS OF CARDIOVASCULAR DISEASES: Diet
      enriched in n-3 fatty acids, especially alpha-linolenic acid, reduces the
      incidence of cardiac death. Studies have shown that alpha linolenic acid prevents
      ventricular fibrillation which is the main cause of cardiac death. Studies in
      rats suggest that alpha-linolenic acid may be more effective in preventing
      ventricular fibrillations than eicosapentaenoic and docosahexaenoic acid.
      Furthermore, alpha-linolenic acid is the main fatty acid decreasing platalet
      aggregation which is an important step in thrombosis i.e. non-fatal myocardial
      infarction and stroke. DIETARY SOURCES AND NUTRITION RECOMMENDATIONS: Dietary
      sources include flaxseed and flaxseed oil, canola oil, soybean and soybean oil,
      pumpkin seed and pumpkin oil, walnuts and walnut oil. Strong evidence supports
      beneficial effects of alpha-linolenic acid and its dietary sources should be
      incorporated into balanced diet for prevention of cardiovascular diseases. The
      recommended daily intake is 2 g with a ratio of 5/1 for linoleic/alpha-linolenic
      acid.

PMID- 15510910
TI  - [Controversies with aspartame].
AB  - INTRODUCTION: Artificial sweeteners are nowadays inevitable food additives, since
      they provide necessary food diversity to people suffering from diabetes.
      Aspartame is the most frequently used artificial sweetener ever and its safety
      profile is much better than that of saccharin or cyclamate. It received marketing
      approval in 1973, but only 3 months later aspartame was withdrawn because of
      allegations based on improperly designed experimental studies dealing with its
      carcinogen effects on rodent brain. However, extensive studies using the same
      model did not confirm such suspicions, and aspartame received a second marketing
      approval. EPIDEMIOLOGICAL STUDIES: Almost two decades later an epidemiological
      study found a relationship between aspartame and an increased frequency of brain
      tumors in humans. However, this study included a short time span of observation,
      and it did not estimate actual intake of aspartame, which led to loss of
      validity. Later on no epidemiological studies found correlation between aspartame
      use and incidence of brain tumors in humans. Up to now the only safety concern
      about aspartame, which received valid scientific proofs, is pro-seizure action of
      its excessive intake. In patients with epilepsy, excessive intake of aspartame
      can decrease the threshold for seizures or prolong them once they appear.
      However, if the intake is not above the recommended level of 40 mg/kg b.w./day,
      aspartame is well tolerated even in this subpopulation. CONCLUSION: Based on
      detailed analysis of published studies on safety of aspartame, it should not be
      restricted, but used in recommended amounts.

PMID- 15510911
TI  - [Ecological significance of electromagnetic fields: the 20th century--century of
      electricity, the 21st--century of magnetism].
AB  - INTRODUCTION: The biosphere consists of all ecosystems of earth and is
      characterized by electromagnetic fields of different frequencies. Physics and
      natural sciences and disciplines are focused on their origin and characteristics.
      NATURAL ELECTROMAGNETIC FIELDS: There is a well defined idea that natural
      electromagnetic activity of the Earth's atmosphere throughout evolution led to
      appearance of electromagnetic homeostasis, i.e. maintenance of inner
      electromagnetic mileu. It can be supposed that during the evolution of living
      organisms natural electromagnetic fields were associated with biochemical
      processes and as a result of natural selection became an important information
      system and obligatory component of life. RESULTS: The results presented here show
      that there is no reason to doubt that natural electromagnetic fields are an
      important ecologic factor. On the contrary, we have to emphasize that natural
      electromagnetic environment is necessary for life on the Earth. Today intensity
      of artificial electromagnetic fields is ten to hundred times higher than of
      natural electromagnetic fields. CONCLUSION: Danger from electromagnetic fields is
      an acute and actual problem which increases knowing that there won't be a spot
      without artificial electromagnetic field on our planet.

PMID- 15510912
TI  - [Acute phenol poisoning].
AB  - INTRODUCTION: Phenol (carbolic acid) is one of the oldest antiseptic agents.
      Currently it is used as a disinfectant, chemical intermediate and nail
      cauterizer. Phenol is a general protoplasmic poison (denatured protein) with
      corrosive local effects. Phenol derivates are less toxic than pure phenol. The
      lethal dose is between 3 to 30 g, but may be as little as 1 g. Phenol is well
      absorbed by inhalation, dermal application, and ingestion. MANIFESTATIONS OF
      ACUTE POISONING: Local manifestations. Dermal exposure produces lesions which are
      initially painless white patches and later turn erythematous and finally brown.
      Phenol produces mucosal burns and coagulum. They cause eye irritation and corneal
      damage. When ingested, it causes extensive local corrosions, pain, nausea,
      vomiting, sweating, and diarrhea. Severe gastrointestinal burns are uncommon and
      strictures are rare. Inhalation produces respiratory tract irritation and
      pneumonia. Systemic manifestations develop after 5 to 30 minutes postingestion or
      post dermal application, and may produce nausea, vomiting, lethargy or coma,
      hypotension, tachycardia or bradycardia, dysrhythmias, seizures, acidosis,
      hemolysis, methemoglobinemia, and shock. MANAGEMENT: Phenol poisoning requires
      immediate medical evaluation, in cases of significant phenol ingestion (more than
      1 g for adults or 50 mg for infants) or symptomatic intoxication. It is necessary
      to establish and maintain vital functions and establish vascular access.
      Treatment includes the following: shock (fluids and dopamine), arrhythmias
      (lidocaine) and convulsions (diazepam). Health personnel should use gowns and
      rubber gloves. Inhalation of 100% oxygen is recommended. Intubate and assisted
      ventilation might be necessary. Metabolic acidosis should be managed by 1 to 2
      mEq/kg of sodium bicarbonate. Methemoglobinemia should be treated if greater than
      30%, or in cases of respiratory distress, with methylene blue 1 to 2 mg/kg of 1%
      solution, slowly i.v. If phenol is ingested, avoid emesis, alcohol and oral
      mineral oil and dilution, because they may increase absorption. Gastric lavage is
      usually not recommended. Immediate administration of olive oil and activated
      charcoal by small bore nasogastric tube is necessary. CONCLUSION: Apart from the
      abovementioned, immediately decontaminate the skin with copious amounts of water
      followed by undiluted polyethylene glycol. Wash the area thoroughly with soap and
      water after treatment. Immediately decontaminate the eyes with copious amounts of
      tepid water for at least 15 minutes. Follow up examination using fluorescein
      stain of eyes for corneal abrasion is recommended

PMID- 15510913
TI  - [Antibiotic resistance].
AB  - INTRODUCTION: After six decades of antibiotic use, the prevalence of antibiotic
      resistant bacteria is increasing, and organisms resistant to almost all
      antibiotics have been identified. ANTIBIOTIC RESISTANCE: It is important to
      understand why antibiotic resistance develops, in order to design strategies for
      its prevention. Factors that promote antibiotic resistance in community and
      hospital settings are: antibiotic selective pressure, prolonged antibiotic
      treatment, inadequate doses, prior use of a less effective drug of the same
      antibiotic class, protected sites or foreign bodies, and poor infection control
      practice. The best available ways to decrease and control antibiotic resistance
      are: rational use of antibiotics (e.g. appropriate selection of drug, dose,
      duration of treatment), good infection control procedures (hygienic practice and
      isolation), as well as local, national and global surveillance networks for
      monitoring dissemination of antimicrobial resistance and detection of new
      resistance mechanisms. CONCLUSION: Clinical guidelines, direct education, and
      regular reports on antibiograms may contribute to more prudent use of
      antibiotics. Overall, the problem of antibiotic resistance is global. However,
      measures need to be taken at an individual, institutional, and ultimately at
      national healthcare level.

PMID- 15510914
TI  - [Effects of platelet single passage on coronary circulation in the isolated
      guinea-pig heart: focus on the L-arginine: nitric oxide system].
AB  - INTRODUCTION: In order to evaluate endothelial response to platelet single
      passage through coronary vascular bed, experiments on isolated guinea-pig hearts
      perfused by the Langendorff method at constant pressure were performed. MATERIAL
      AND METHODS: Platelet single passage was performed with platelet-rich plasma
      obtained from healthy volunteers, as well as from patients with acute myocardial
      infarction. Hearts, isolated from guinea-pigs of either sex were perfused with
      Krebs-Hensenleit buffer. After a stabilization period of 30 minutes at 70 cm H2O,
      coronary perfusion pressure decreased to 30 cm H2O and increased to 120 cm H2O.
      After basic protocol, hearts were perfused with PRP, PRP-AMI alone or in
      combination with nitric oxide synthase inhibitor, N(omega)-nitro-L arginine
      methyl ester (L-NAME)--30 M, and nitrite outflow (NO2-) was measured. RESULTS:
      Basal (at 70 cm H2O) coronary flow (CF) and NO2- was 4.71+/-0.43 ml/min and
      0.55+/-0.13 nmol/min/g wt. PRP induced significant decrease of CF at all values
      of CPP (from 32% at 30 cm H2O to 27% at 120 cm H2O), with parallel NO2- reduction
      (from 25% to 28%). When L-NAME, 30 M was added, PRP was much less effective: CF
      was reduced from 13% to 5%, with parallel changes of NO2- (reduction of 10% at
      all CPP values). PRP-AMI induced higher degree of CF reduction (from 42% to 44%)
      with NO2 reduction from 23% to 35%. PRP-AMI after applied L-NAME induced also
      less CF-reduction (from 18% to 12%), with similar NO2- reduction (from 18% to
      12%). CONCLUSION: Our findings show that effects of platelet single passage
      through coronary vascular bed should be affected by NO in isolated guinea-pig
      hearts.

PMID- 15510915
TI  - [Relaxant effects of protamine sulfate on isolated renal arteries of normotensive
      and hypertensive rats].
AB  - INTRODUCTION: Protamine sulfate is found to have endothelium-dependent relaxing
      effect on isolated blood vessels. The aim of our experiments was to study
      relaxant effects of protamine sulfate on isolated renal arteries of both
      normotensive and hypertensive rats. MATERIAL AND METHODS: Experiments were
      performed on renal arteries, isolated from male, Wistar, spontaneously
      hypertensive rats (250-300 g). The adhering perivascular tissue was carefully
      removed from arteries which were then cut into 3-5 mm ring segments, incubated 30
      min in water bath in Krebs-Ringer bicarbonate solution at 36 degrees C, and
      gassed with 95% O2 and 5% CO2. Each was gradually stretched to optimal tension (2
      g) and isometric transducer registered mechanical contractions. Contractions of
      isolated blood vessels were caused by phenylephrine (10(-6) mol) and functional
      integrity of the endothelium was confirmed by acetylcholine (10(-5) mol) and
      histopathological examination. RESULTS AND DISCUSSION: Preparations were analyzed
      using a microscope to distinguish differences between blood vessels of
      normotensive and hypertensive rats. The reason for this effect of protamine is
      probably its stimulating effect on nitrogen-monoxide release, which might be the
      main reason for systemic hypotension that occurs during protamine infusion. It
      occurs due to activation of endothelial NO-synthesis. Our results show a better
      relaxant effect of protamine with normotensive, comparing to hypertensive rats,
      regarding to better preservation of endothelium with normotensive animals.
      CONCLUSION: The relaxant effect of protamine occurs due to NO release with
      conductance artery, which is not the case with microvessels, where this effect
      occurs due to endothelium-derived hyperpolarizing factor release.

PMID- 15510916
TI  - [Aging and hypertension as factors of progressive renal failure].
AB  - INTRODUCTION: This study evaluated the effects of aging on renal hemodynamic,
      biochemical and histological parameters in spontaneously hypertensive rats.
      MATERIAL AND METHODS: Systolic blood pressure was measured in male SHR (adult-
      adSHR and aged--agSHR) during four weeks, indirectly, once a week At the end of
      the experiment 24 h urine samples were collected and hemodynamic measurements
      were performed. Animals were sacrificed and blood samples were collected for
      biochemical analysis. The left kidney was histopathologically examined. RESULTS
      AND DISCUSSION: Our results show that there is no difference in systolic blood
      pressure between adult and aged SH rats. Renal blood flow was significantly
      decreased (0.68+/-0.08 vs. 0.99+/-0.007 ml/min/100 g b.w.), while renal vascular
      resistance increased by 28.90% in aged gSH rats. Plasma creatinine (Pcr) level
      was decreased in agSHR compared to adSHR (p<0.001). There was no difference in
      creatinine clearance, because urine volume was significantly increased in the
      aged rats (p<0.001). Protein excretion (Pex) and filtration fraction were
      significantly increased in aged rats compared to adult rats (Pex: p<0.001, and
      FF: p<0.05). The degree of focal-segmental glomerulosclerosis measured by a
      semiquantitative histological technique was significantly increased in the aged
      rats compared to adult. Sporadic focal tubular atrophy and dilatation with
      periodic acid-schiff positive material were present in the aged group. Also there
      were changes in structure of afferent arterioles and small vessels with
      myointimal proliferation and reduced lumen diameter. There were no changes in
      lumen diameter of large renal vessels. Histopathological score of adult rats
      showed only minimal changes in vessel structure. CONCLUSION: These results show
      that aging, and long-term high arterial blood pressure are risk factors
      associated with hemodynamic changes in renal arteries and kidney vessels,
      advancement of glomerulosclerosis and tubular injury, and therefore may
      contribute to progression of renal failure and eventually cause end stage renal
      disease.

PMID- 15510917
TI  - [Binding of natural IgM autoantibodies DJ to T-lymphocytes and T-cell hybridomas
      and its possible role in apoptosis].
AB  - INTRODUCTION: Natural autoantibodies can recognize self-antigens expressed on
      damaged cell membranes and participate in their elimination from the body and
      maintainance of homeostasis. It has been shown earlier that human monoclonal
      immunoglobulin M DJ isolated from sera of patients with Waldenstrom
      macroglobulinemia, possesses characteristics of natural antibodies/autoantibodies
      and binds to phosphoryl choline. In this paper we analyzed binding of IgM DJ to
      the membrane of thymocytes, T-lymphocytes derived from lymph node and to T-cell
      hybridomas. MATERIAL AND METHODS: Human monoclonal IgM antibodies were isolated
      by means of euglobulin precipitation and used for immunization of BALB/c mice. T
      lymphocytes were isolated from lymph nodes and stimulated by antigen or
      Concanavalin A, used as a mitogen. For obtaining T-T hybridoma, fusion was done
      with BW 5147 cell line. Binding of IgM DJ to T-lymphocytes and T-hybridomas was
      detected by flow cytometry. RESULTS: We presented IgM DJ binding to the membrane
      of thymocytes and lymphocytes of the lymph nodes from nonimmunized mice. Binding
      with similar characteristics was demonstrated for T-lymphocytes isolated from
      lymph nodes from immunized mice before in vitro stimulation, which significantly
      increased after stimulation either by mitogen or by antigen. The highest level of
      binding of IgM DJ was obtained in the population of in vitro cultivated
      lymphocytes, not stimulated in vitro. By analyzing cells which bound IgM DJ, it
      has been established that the examined cell population presented with
      characteristics of cells undergoing apoptosis. CONCLUSION: These results indicate
      that IgM DJ can be involved in maintenance of homeostasis by elimination of cells
      expressing phosphoryl choline during apoptosis.

PMID- 15510918
TI  - [Effects of molsidomine on changes in oxidant/antioxidant status of rat
      erythrocytes].
AB  - INTRODUCTION: Molsidomine (MO) is an established drug in treatment of coronary
      heart disease. Considering that MO is a donor of nitric oxide (NO) and a
      superoxide anion radical (O2*-), which forms peroxynitrite, a very toxic radical,
      the aim of this study was further elucidation of molecular mechanisms of MO
      action, particularly effects on prooxidative-antioxidative status of rat
      erythrocytes. MATERIAL AND METHODS: Rat (Wistar albino, male, 250-300 g of b.m.)
      erythrocyte suspensions were aerobically incubated (120 min, 37 degrees C)
      without (control) or with MO (0.1, 0.25, 0.5, 1.0 and 1.5 mM). Concentrations of
      reactive oxygen species, methemoglobin, Heinz bodies, lipid peroxides, vitamins
      and glutathione, as well as activities of enzymes of the antioxidative defense
      system (AOS) were evaluated using standard techniques. RESULTS AND DISCUSSION:
      Molsidomine increases nitrite concentrations (indicating NO+ level),
      hydroxylamine (indicating NO- level), 3-nitro-tyrosine (indicating ONOO- level)
      and H2O2, but decreases O2*- level in a dose-dependent manner (changes are
      statistically significant only with high doses of molsidomine--1.0 and 1.5 mM).
      These alterations were followed by partial cells damage, increased formation of
      Heinz bodies, but there were no changes in MetHb and lipid peroxide levels. The
      defense response of erythrocytes to evident oxidative stress includes increased
      Vitamin E and Vitamin C concentrations (nonenzymatic components ofAOS), as well
      as decreased glutathione (reduced and oxidized) levels. Activities ofAOS enzymes
      remain unchanged. CONCLUSION: Experimental doses of MO induce oxidative stress in
      rat erythrocytes. However, the first line of AOS is successful in the cellular
      defence response.

PMID- 15510919
TI  - [Hepatoprotective effects of silymarin in androgenic-anabolic steroid-induced
      liver damage].
AB  - INTRODUCTION: The use and abuse of anabolic-androgenic steroids (AAS) commonly
      induces liver damage. MATERIAL AND METHODS: The study included 40 male Wistar
      rats, divided into 4 groups of 10 rats each. Animals in the first experimental
      group (M), were subjected to progressive systematic forced swimming test, 5 days
      a week, during 8 weeks. Animals in this group were treated with AAS
      methandienone, 2 mg/kg BW/day, per os, before swimming, 5 d/w for 8 weeks. After
      swimming, animals were given three times more food than the laboratory animals of
      the same age and kind. Animals in the second group (M+S), were subjected to
      progressive forced swimming test, 5 d/w 8 weeks. Animals in this group were
      treated with methandienone equally as the experimental group M and received the
      same amount of food. Apart from that, they received silymarin 20 mg/kg BW/day.
      Animals in the third group (K), represented the control group, which was neither
      subjected to swimming test, nor treated with methandienone or silymarin. Animals
      in this group received the same amount of food as animals in groups M and M+S.
      Animals in the fourth group (C), also represented a control. This group was not
      exercised nor treated, and animals received a standard amount of food for
      laboratory animals of this kind and age. Quantitative analysis of obtained
      hemataxylin-eosin, periodic acid shift and enzymohistochemical preparations was
      processed using Digital Image Analysis System: Microimage 3.0. RESULTS: It was
      established that processes in the nuclei of animals in groups M and K were
      significantly more intensive (p<0.001) in relation to groups M+S and C. The
      investigation of glycogen showed significantly higher density in the cells of
      groups M and M+S in comparison to groups K and C. Also, there was a significant
      difference between groups M+S and M. Density of enzyme activity of glutamate
      dehydrogenase in hepatocytes of animals in the group M+S was significantly higher
      in relation to the remaining three groups. A statistically significant difference
      was not found in enzyme activity of succinate dehydrogenase and lactate
      dehydrogenase. DISCUSSION: In cell nuclei of animals in the experimental group M,
      in the absence of silymarin effect, methandienone causes damages which induce
      regenerative processes and in this way increase high intensity activity.
      Silymarin significantly increases the glycogen density in hepatocytes. Increased
      activities of GDH are attributed to cell vitality. CONCLUSION: The present
      results show hepatoprotective effects of silymarin in androgenic-anabolic steroid
      induced liver damage.

PMID- 15510920
TI  - [Common carotid artery intima-media thickness, carotid atherosclerosis and
      subtypes of ischemic cerebral disease].
AB  - INTRODUCTION: Common carotid artery intima-media thickness (CCA-IMT) measurements
      are widely used to study atherosclerosis. CCA-IMT is a useful outcome measure in
      clinical studies and intervention trials because it reflects early stages of
      atherosclerosis and cardiovascular risk. The present study examined the
      relationship between common carotid artery intima-media thickness and ischemic
      brain infarction. MATERIAL AND METHODS: The present study examined the
      association between CCA-IMT and incidence of ischemic stroke and its subtypes in
      75 cases and 21 controls. Cases with internal borderzone infarction (IBI) were
      consecutively recruited and classified into subtypes using CT and Bamford's
      classification. It classifies cerebral infarctions regarding vascular territory
      using clinical features to determine the size and site of infarction. These
      subtypes included: total anterior circulation infarctions (TACIs), partial
      anterior circulation infarctions (PACIs), posterior circulation infarctions
      (POCIs), and lacunar infarctions (LACIs). Controls were recruited among
      individuals hospitalized at the same institution and matched for age and sex.
      Patients and control subjects underwent B-mode ultrasonographic measurements of
      IMT of the far wall of both common carotid arteries. RESULTS: Of 75 patients with
      acute ischemic stroke, 10 (14%) were classified as TACIs, 34 (45%) had PACIs, 12
      (16%) had POCIs and 19 (25%) had LACIs. Mean CCA-IMT was higher in investigation
      group (1.03+/-0.18 mm) than in controls (0.85+/-0.18 mm; p<0.0001). The
      difference in CCA-IMT between investigation group and controls was significant
      and the relation between CCA-IMT and IBI remained unchanged after adjustments of
      main cardiovascular risk factors. Regarding the subtypes of IBI, IMT values were
      significantly higher in patients with TACIs and PACIs versus those with LACIs and
      POCIs. CONCLUSIONS: An increased CCA-IMT was established in all subtypes of IBI
      and was significantly higher in those with anterior circulation infarctions
      versus posterior circulation and lacunar infarctions. This study points to
      importance of noninvasive measurement of CCA-IMT with ultrasonographic techniques
      as a diagnostic tool for selecting patients at high risk for IBI and identifying
      different subtypes of ischemic stroke.

PMID- 15510921
TI  - [Hypokinesia: a health related risk factor].
AB  - INTRODUCTION: Results of numerous epidemiological and experimental studies show
      that insufficient physical activity (hypokinesia) is an important factor in
      development of chronic degenerative diseases. It has been proved that
      insufficient physical activity aggravates insulin resistance, a latent and
      asymptomatic metabolic disorder that causes hyperinsulinemia. On the other hand,
      there are multiyear, multidiscipline, prospective clinical studies which have
      established a significant correlation between general physical ability (measured
      by maximal oxygen consumption: VO2max) and the capability of metabolic system to
      produce energy: physical fitness=metabolic fitness. DIAGNOSIS: It is possible to
      precisely diagnose the newest, up to now inaccessible risk factor for health. Our
      attitude is that measurement of VO2max has to be a standard practice.
      Quantification means precise diagnosis of hypokinesia. Physical activity for
      preventive and therapeutic purposes is rational, effective and optimal way. It
      makes it possible to choose adequate therapy programs and their dosage
      (intensity, volume, form and duration). We can follow-up therapy effects,
      achievements and maintain our goal (medium level of general aerobic ability).
      CONCLUSION: Low aerobic ability should be treated as a significant independent
      risk factor for development of insulin-independent diabetes and arteriosclerosis.
      At the same time this risk factor can easily be affected using natural,
      physiological mechanisms which are favorable, but simple, inexpensive and
      practically lifelong.

PMID- 15510922
TI  - [Phagocytic activity of peripheral blood leukocytes during acute myocardial
      infarction].
AB  - INTRODUCTION: Coronary occlusion may cause acute myocardial infarction associated
      with many cellular and humoral disturbances of the immune system. The aim of this
      investigation was to examine phagocytic activity of peripherial blood monocytes
      and neutrophils as potential cellular markers of systemic immunological events in
      acute myocardial infarction. MATERIAL AND METHODS: This study included thirty
      patients following first acute myocardial infarction and thirty healthy
      volunteers. Immunological analyses were performed on admission and repeated on
      the second and seventh days after the acute event. Monocytes and neutrophils were
      obtained from heparinized whole blood after centrifugation and separation on
      density gradient and incubated with fixed number of heat inactivated and painted
      particles of yeast. We investigated the following parameters of phagocytic
      activity: percentage of phagocytosis, phagocytic index, absolute phagocytic
      index, phagocyte count in a fixed volume of peripherial blood and phagocytic
      capacity. RESULTS: Except phagocytic index, all phagocytic parameters of
      monocytes and neutrophils were increased in acute myocardial infarction patients
      on admission and on the second day of hospitalization. On the seventh day after
      acute event only the mononuclear phagocyte count in fixed volume of peripheral
      blood showed significant increase in acute myocardial infarction patients, while
      percentage of phagocytosis, phagocyte count in fixed volume of peripheral blood
      and phagocyte capacity of neutrophils were increased during the whole
      investigated period. CONCLUSION: These data suggest that acute myocardial
      infarction was followed with strong systemic inflammatory response to myocardial
      damage. Furthermore, activated monocytes and neutrophils could be a significant
      source of free radicals, which might be involved in lipid peroxidation and cause
      tissue damage in early postinfarction period.

PMID- 15510923
TI  - [The phagocytic activity of monocytes in different stages of breast cancer].
AB  - INTRODUCTION: Defective monocyte function has been associated with a variety of
      human malignancies. However, the diagnostic and/or prognostic significance of
      this disturbance remains unclear. MATERIAL AND METHODS: The number of leukocytes,
      proportion and absolute number of granulocytes, lymphocytes and monocytes, and
      monocyte phagocytic function were determined in a group of 30 patients with
      invasive ductal breast cancers. Cancer patients were divided into 3 groups on the
      basis of clinical stage of the disease: group A--patients with localized disease;
      group B--patients with regional lymph node metastases; group C--patients with
      distant metastases. The control group consisted of 10 age-matched healthy women.
      RESULTS: This study demonstrates that patients with breast cancer have a
      significant decrease in the absolute number of monocytes and phagocytic activity.
      Moreover, compared to healthy individuals, the absolute number of monocytes
      decreases in cancer patients, reaching the lowest value in patients with distant
      metastases (group C). Similarly, phagocytic activity of peripheral blood
      monocytes was significantly lower in patients with tumors. Index of phagocytosis
      showed a two-fold, and capacity of phagocytosis a seven-fold decrease in advanced
      stage patients (C). DISCUSSION AND CONCLUSION: The phagocytic activity reveals
      the dynamics of the host tumor interface. This method is used alone or combined
      with other methods as an indicator of the extent or activity of the disease. We
      conclude that monocyte phagocytic function can be used as an additional
      prognostic factor in breast cancer monitoring.

PMID- 15510924
TI  - I'm embracing my inner curmudgeon.

PMID- 15510925
TI  - Seniors and the city.

PMID- 15510926
TI  - We've got rhythm.

PMID- 15510927
TI  - Non-invasive determination of left ventricular relaxation time constant by
      Transthoracic Doppler echocardiography.
AB  - BACKGROUND: Left ventricular (LV) relaxation time constant (Tau) is a relatively
      load-independent index of diastolic function in the evaluation of heart failure.
      However, the requirement of high-fidelity intraventricular pressure recording
      limits its clinical utility. In the present study, we investigated whether Tau
      could be estimated noninvasively. METHODS: Thirty-seven patients indicated for
      cardiac catheterization were recruited for study. Echocardiography and cardiac
      catheterization with high-fidelity LV pressure recording were performed
      sequentially within 1 hour. The non-invasive TauDopp was derived from the
      formula: TauDopp = IVRT(Dopp)/[ln(Ps) - ln(10)], where IVRT is the isovolumic
      relaxation time measured by Doppler echocardiography and Ps is systolic blood
      pressure measured during the echocardiographic examination. The invasive TauLM
      was determined by non-linear least-square parameter estimate technique, using the
      exponential equation: Pv = Poe(-t/Tau) + b, where Pv is the instantaneous LV
      pressure, P0 is LV pressure at minimal dP/dt, and b is the theoretical asymptote.
      The difference between TauDopp and TauLM was compared using paired t-test, and
      their relation was evaluated using simple correlation and intra-class correlation
      coefficient. RESULTS: IVRT(Dopp) was significantly correlated with the invasively
      derived IVRT (r = 0.42, p = 0.012). The completely non-invasive TauDopp was
      significantly correlated with the direct curve-fitted TauLM (r = 0.41;p = 0.013),
      and the intraclass correlation coefficient was 0.29 (p = 0.04). In addition,
      TauDopp was significantly smaller than TauLM (36+/-6 ms vs. 57+/-15 ms, p <
      0.001). CONCLUSIONS: Tau can be estimated noninvasively by transthoracic Doppler
      echocardiographic method with limited accuracy. The clinical utility of TauDopp
      remains to be determined.

PMID- 15510929
TI  - Significance of pulmonary venous obstruction in total anomalous pulmonary venous
      return.
AB  - BACKGROUND: Total anomalous pulmonary venous return (TAPVR) is an uncommon
      congenital cardiovascular anomaly with poor natural prognosis. It has been
      detected more frequently in recent year due to the advent of echocardiography and
      cardiovascular magnetic resonance imaging (MRI). The aim of this study was to
      evaluate the clinical manifestations and outcomes in TAPVR patients with or
      without pulmonary venous obstruction (PVO). METHODS: From January 1985 to
      December 2002, a total of 27 cases with TAPVR at our institution were reviewed.
      Accurding to the preseace or assence of PVO, patients were divided into PVO group
      and non-PVO group. Patients' sex, age at diagnosis, types of TAPVR, clinical
      manifestations, surgical treatment and outcomes were evaluated. RESULTS: All of
      them had received 2-dimensional (2-D) and color Doppler echocardiography
      examination. Cardiac catheterization was performed in all but 1 patient who died
      at the first day of birth. In addition, 10 of 27 cases had cardiovascular MRI for
      further study. The number of cases in PVO group and non-PVO group were 15 (56%)
      and 12 (44%), respectively. There was no significant difference in sex or
      pulmonary venous drainage sites between both groups. Cyanosis was more prevalent
      in the PVO group (80% vs. 30%, p = 0.038). Four (27%) cases PVO group and 3 (25%)
      cases of the non-PVO group had of the non-isolated cardiac lesions. Pulmonary
      hypertension was present in 18 (69%) of 26 cases who had received cardiac
      catheterization. Among them, 10 had PVO and 5 had systemic level of pulmonary
      arterial pressure. Seven (30%) of 23 patients who had received operation died; in
      contrast, 3 of 4 patients without operation expired. The remaining 1 did not had
      surgery because of complex heart disease. There was no significant difference in
      surgical mortality between PVO and non-PVO groups (33% vs. 27%). CONCLUSIONS:
      Cyanosis is an obvious clinical symptom of obstructed TAPVR. Surgical mortality
      made no significant difference between obstructed and non-obstructed groups.
      Early detection and surgical treatment for TAPVR are important. Although cardiac
      catheterization and angiocardiography is the golden standard for the diagnosis, 2
      D and color Doppler echocardiography can also provide quick and accurate
      diagnostic images of TAPVR.

PMID- 15510928
TI  - Interleukin-2 stimulation activates mesothelial cellular functioning against
      autologous tumor cells.
AB  - BACKGROUND: The present study was designed to determine the different effects of
      cytokines or antibodies (IL-2, IL-4, IL-7, IL-10, IL-12, alphaCD3) in stimulating
      the cellular functions of mesothelial cells isolated from malignant pleural
      effusion. METHODS: Mesothelial cells were isolated from 27 patients with
      malignant pleural effusion. The cultured cellular interferon-gamma (IFNgamma) and
      IL-10 production, proliferative response, and cytolytic activity against
      autologous tumors and K-562 cells were measured. RESULTS: Stimulation with IL-2
      alone significantly increased the mesothelial cells' proliferative response (p <
      0.001) and cytolytic activity against autologous tumors (p = 0.025). The further
      addition of other cytokines did not increase these functions. The IFNgamma/IL-10
      ratio data showed that the T-helper (Th) pathway was shifted from the Th-2
      pathway to the Th-1 pathway (increase of IFNgamma/IL-10 ratio) when mesothelial
      cells were stimulated with IL-2. Further stimulation with IL-2 plus IL-12 or
      alphaCD3 shifted the Th pathway further in the Th-1 direction, but without
      statistical significance. CONCLUSIONS: The mesothelial cell proliferative
      response is enhanced with IL-2 stimulation alone. The T-helper pathway is also
      shifted from the Th-2 to the Th-1 response (increase of IFNgamma/IL-10 ratio)
      after IL-2 stimulation of mesothelial cells. Mesothelial cells had cytolytic
      activity against tumor cells, and this activity could be augmented by IL-2
      stimulation.

PMID- 15510930
TI  - Effect of continuous administration of conjugated estrogen plus
      medroxyprogesterone acetate (Premelle) in postmenopausal women in Taiwan.
AB  - BACKGROUND: To compare the metabolic effects on lipids and acceptability and
      safety of, and compliance with, a continuous administration of conjugated
      estrogen plus medroxyprogesterone acetate (Premelle) versus a placebo in non
      hysterectomized postmenopausal women. METHODS: Sixty-six generally healthy,
      female, early post-menopausal women, from 45-60 years of age, were randomized for
      an administration of conjugated estrogen plus medroxyprogesterone acetate
      (Premelle, Premarin 0.625 mg plus medroxyprogesterone acetate 2.5 mg/tablet
      orally) or a placebo for 6 months. The changes in each patient's lipid profiles
      from baseline, the frequency of hot flushes, bleeding occurrences, and
      climacteric symptoms, were evaluated. Safety was monitored by means of physical
      examination, Papanicolau smear, transvaginal ultrasonography, and laboratory
      check-up. Adverse events were also recorded. RESULTS: The difference before and
      after treatment in serum LDL-C and total cholesterol (TC) was statistically
      significant in the Premelle group (LDL-C, p = 0.006, TC, p = 0.040). No
      statistically significant difference in the change from baseline was observed in
      the levels of LDL-C and TC in the placebo treatment group. There was a
      statistically significant change from baseline in menopausal symptoms, which were
      evaluated by the Greene Climacteric Scales in the Premelle group. There was no
      clinically significant finding in the physical examination, vital signs,
      laboratory data, or endometrial thickness in either treatment group. The
      difference in the number of patients who reported an adverse event was not
      statistically significant between the 2 treatment groups. CONCLUSIONS: This study
      demonstrated that Premelle was effective in decreasing LDL-C and total
      cholesterol levels, and also showed an improvement in some menopausal symptoms,
      such as vasomotor and sexual dysfunction symptoms. No significant bleeding was
      observed with Premelle, which was well tolerated in this study. The results of
      this study could support the use of Premelle tablets as a convenient alternative
      hormone therapy.

PMID- 15510931
TI  - The experience with Ritleng intubation system in patients with congenital
      nasolacrimal duct obstruction.
AB  - BACKGROUND: To report the clinical experience and success rate with Ritleng
      intubation system in patients with congenital nasolacrimal duct obstruction.
      METHODS: Twenty-four patients (32 eyes) with congenital nasolacrimal duct
      obstruction treated with the Ritleng intubation system were enrolled in this
      study. The mean age was 20.1+/-9.6 months. The technique involved introduction of
      a Prolene monofilament guide thread, securely fastened to silicone tubing, into a
      tubular metal probe that opened into the inferior meatus. Success was defined as
      complete resolution of previous symptoms and a normal result of dye disappearance
      test in cooperative patients. To establish relationship of success rate with
      patients' ages, these data were compared and analyzed. RESULTS: All eyes were
      successfully intubated with the Ritleng system. The Prolene monofilament
      spontaneously emerged from the nose in 19 (60%) of 32 eyes, making retrieval
      simple and uncomplicated. The overall success rate (of all aged groups) was 90%.
      In the group over 24 months of age, there was no significant decrease in the
      success rate (p > 0.1), but obvious difficulty in intubation and lengthy
      operation time were noted. CONCLUSIONS: Silicone intubation with the Ritleng
      system is an effective treatment for patients with congenital nasolacrimal duct
      obstruction, especially at young age. Comparing with conventional metal probe
      system, there was minimal nasal bleeding and trauma to the nasal mucosa with
      Ritleng intubation system. With the advantage of easy retrieval, operation time
      can be shortened, thereby improving patient care and decreasing potential
      morbidity.

PMID- 15510932
TI  - Single photon emission computed tomography (SPECT) for low back pain induced by
      extension with no root sign.
AB  - BACKGROUND: Low back pain (LBP) is very common in the general population. Most
      patients with LBP will receive an X-ray examination on lumbar spine; however, the
      results are likely to show a negative finding or degenerative joint disease,
      which are not truly pathological factors. Among various imaging diagnostic tools
      for active bony lesions of lumbar spine, planar bone scintigraphy has a higher
      sensitivity, but its ability to locate anatomic lesions is less satisfactory. The
      purpose of this study was to investigate the role of SPECT for evaluation of LBP.
      METHODS: Fifty-two consecutive patients who had low back pain induced by
      extension were studied. They had no evidence of malignant tumor, immune disease,
      spinal infection and neurological disorder by history-taking and physical
      examination. All patients received planar bone scintigraphy and SPECT exams
      following an X-ray examination. The results of X-ray finding were grouped into 3
      categories: (A) normal; (B) degenerative joint arthritis; (C) spondylolysis. The
      data of test results and clinical evaluation were then used for analysis.
      RESULTS: Twenty (38.5%) out of 52 patients examined by planar scan had
      abnormality, with 29 increased uptake lesions, compared with 28 (53.8%) out of 52
      patients with 60 increased uptake lesions by SPECT with planar scan; SPECT
      disclosed 1-2 more lesions with improved location in 15 patients (p < 0.05). Of
      the 52 patients, 21 (40.4%) presented in group A, 21 (40.4%) in group B, and 10
      (19.2%) in group C according to the X-ray examination. In group A, 9 out of 21
      (42.9%) patients had an abnormal SPECT result, compared to 5 of 10 (50%) in group
      B, and 14 out of 21 (66.7%) in group C, respectively (p > 0.05). The location of
      abnormal uptake on L-spine included vertebral body and arch (57.1%), vertebral
      arch (28.6%), and vertebral body (14.3%). Most of lesions (91.5%) were
      distributed at the 4th and 5th lumbar vertebral segments. CONCLUSIONS: SPECT was
      more sensitive and located more lesions than planar bone scintigraphy, especially
      when the lesions were located at posterior element of vertebrae. Most of the
      lesions were distributed at the 4 th and 5 th lumbar vertebral segments. There
      was no significant statistical difference of abnormal SPECT related to X-ray
      finding. The use of SPECT was the first choice among all image modalities when
      cause of low back pain was assumed to arise from bone and joint disorder at
      clinical evaluation.

PMID- 15510933
TI  - Severe hypophosphatemia in a patient with diabetic ketoacidosis and acute
      respiratory failure.
AB  - Although hypophosphatemia is a common complication during therapy of diabetic
      ketoacidosis, it is seldom severe and rarely causes clinical manifestations. We
      report a 39-year-old woman with diabetic ketoacidosis who developed acute
      respiratory failure after therapy. Although hyperglycemia and acidosis were
      corrected after treatment, respiratory distress and weakness still persisted. The
      chest radiograph showed no active lung lesion. Brain CT revealed no significant
      abnormality. Echocardiographic study revealed normal LV systolic wall motion.
      Blood biochemistry demonstrated severe hypophosphatemia of 0.3 mg/dL (normal
      value: 2.5 to 4.5 mg/dL). Phosphate replacement therapy with potassium phosphate
      was given. The patient's clinical condition improved steadily over the next few
      days, and after 4 weeks of hospitalization, she was discharged home without
      obvious long-term sequelae. In a critically ill patient, the symptoms of
      hypophosphatemia are not apparent and may mimic the symptoms of other underlying
      disease. Although phosphate replacement is not recommended routinely in diabetic
      ketoacidosis, if the patient develops cardiopulmonary distress, anemia or severe
      hypophosphatemia, phosphate therapy under close surveillance is indicated.

PMID- 15510934
TI  - Recurrent pulmonary embolism in an elderly patient with Cushing's syndrome,
      adrenocortical adenoma, pheochromocytoma and prostate adenocarcinoma.
AB  - Pulmonary embolism (PE) is a major health problem. Mortality in untreated PE is
      high, but with adequate (anticoagulant) treatment, can be reduced. Multiple
      primary and secondary risk factors are responsible for PE. But there is rare
      association of mixed adrenal tumor with PE. Here, we report a case of
      adrenocortical adenoma with Cushing's syndrome coexistent with pheochromocytoma
      with recurrent PE in an elderly patient with prostate adenocarcinoma. A 78-year
      old Taiwanese retired veteran was admitted in July, 2002 with the presentation of
      syncope. Three years before, he was diagnosed with prostate adenocarcinoma and
      had received Androcur therapy since then. Five months later, he was admitted with
      Cushingoid appearance and hypertension. Abdominal imaging studies revealed a left
      adrenal tumor. Laparoscopic adrenalectomy revealed an adrenocortical adenoma. Two
      years later, a recurrent left adrenal tumor was found. Repeated laparoscopic
      adrenalectomy revealed pheochromocytoma. One month after the repeat laparoscopic
      surgery, the patient was admitted due to syncope. Chest X-ray revealed
      cardiomegaly with pulmonary venous congestion. Echocardiogram showed impaired
      right ventricle global systolic function. Perfusion lung scan showed a high
      probability of PE. Heparin and coumadin were given but stopped 5 weeks later due
      to the development of severe skin ecchymosis. In December 2002, the patient was
      admitted again with consciousness disturbance. Chest computed tomography (CT)
      revealed bilateral PE, and he died 5 hours later due to cardiogenic shock. In
      conclusion, in elderly patients with Cushing's syndrome with pheochromocytoma and
      prostate carcinoma, there is probability of pulmonary embolism.

PMID- 15510935
TI  - Prenatal sonographic findings in a fetus with congenital isolated ileal atresia.
AB  - Most cases of isolated nonduodenal bowel atresia are thought to be due to
      ischemic events from hypotension, vascular accident, volvulus, intussusception
      and cocaine. We present a case of isolated ileal atresia suggested using results
      of prenatal sonography which showed multiple markedly dilated fluid-filled
      intestinal loops with changeable shapes and positions secondary to active
      peristalsis. Postnatal oral contrast radiography demonstrated obstruction located
      at the ileal level. Exploratory laparotomy confirmed isolated ileal atresia.
      Primary end-to-end anastomosis was done. The infant endured the procedure well.
      Cases with multiple intestinal atresia always have fatal prognosis, even after
      surgery. Cases of isolated intestinal atresia usually have better prognosis and
      deserve more attention. Early diagnosis and early intervention are both important
      for good outcomes.

PMID- 15510936
TI  - Bilateral dorsal defect of patellae with patellar hypoplasia and patellofemoral
      malalignment.
AB  - Dorsal defect of the patella (DDP) is an uncommon but well-documented disease
      entity. We report a case of bilateral DDP with patellar hypoplasia and patello
      femoral malalignment. Detailed imaging features including radiographic, magnetic
      resonance imaging, and computed arthrotomographic appearances, are described.

PMID- 15510937
TI  - Angiofibroma of the hypopharynx.
AB  - Primary extranasopharyngeal angiofibroma is very rare. To date, approximately 60
      cases have been reported in the English literature. Only 1 case was confined to
      the posterior wall of hypopharynx. In August 2000, a 68-year-old man presented
      with a 6-month history of progressive foreign-body sensation in the throat and
      intermittent inspiratory stridor. Endoscopic examination of the larynx and
      pharynx revealed a nonpulsatile, pink-grayish, polypoid mass arising from the
      posterior pharyngeal wall of the left hypopharynx. Under general anesthesia, this
      tumor mass was subsequently removed by the endoscopic CO2 laser. The histologic
      diagnosis was an angiofibroma. Three-year follow-up found no evidence of tumor
      recurrence or post-operative complications.

PMID- 15510938
TI  - Bacterial disease in HIV-infection.

PMID- 15510939
TI  - Bacterial infections in children with HIV/AIDS.
AB  - HIV/AIDS affects over 850,000 children in Africa. Bacterial infections are
      frequent in this group of children. Pneumonia, meningitis and septicaemia are
      especially common, recurrent and most often caused by Streptococcus pneumoniae.
      Salmonella spp are the most frequently isolated causative agent of septicaemia in
      malarial areas. Soft tissue, eye and oral infections have a higher incidence in
      HIV-infected than uninfected children. In all instances the causative agents are
      not dissimilar from those that cause disease in HIV-uninfected children, but the
      mortality is greater. Increased bacterial resistance to first line antibiotics
      has been reported and the use of cotrimoxazole prophylaxis may further influence
      the resistance pattern of common bacteria.

PMID- 15510940
TI  - Non-typhoidal salmonella bacteraemia--an under-recognized feature of AIDS in
      African adults.
AB  - Non-typhoidal salmonella (NTS) infections are severe, invasive and recurrent in
      the HIV-infected adult, and NTS are the commonest cause of hospital admission
      with bacteraemia in sub-Saharan Africa. NTS bacteraemia typically presents in
      patients with HIV/AIDS once the CD4 count falls below 200 cells/microL. In
      patient mortality is 35%-60%, and is highest in patients with confusion or severe
      anaemia. Among survivors, 25%-45% may have single or multiple recurrences of NTS
      bacteraemia 1-6 months after the first illness, requiring retreatment. Diagnosis
      relies on blood culture, so in many areas this disease cannot be definitively
      diagnosed, and must be empirically treated. Treatment is guided by local
      antibiotic sensitivities; fluoroquinolones are particularly useful for initial
      treatment if there is multidrug reistance to other agents, and may result in
      lower recurrence rates than other agents. Where possible, long-term secondary
      chemoprophylaxis to prevent recurrence is advisable. Successful ARV treatment
      also prevents recurrence. There is inadequate knowledge about the epidemiology of
      carriage and transmission among at-risk populations.

PMID- 15510941
TI  - Pneumococcal infections in HIV infected adults--clinical features, reasons behind
      the association and future hopes for prevention.
AB  - Streptococcus pneumoniae is the most important bacterial cause of pneumonia and
      meningitis among adults world wide. It is a particularly common cause of these
      infections and also bacteraemia among HIV infected adults with rates of disease
      increasing to more than 100 times the normal as HIV infection progresses to AIDS.
      This article briefly describes the common presentations and outcomes of
      pneumococcal disease (PD) in HIV infected adult inpatients in Malawi. Factors
      underlying susceptibility to pneumococcal infection in HIV infected adults are
      then reviewed, along with the effectiveness of current vaccines. Finally, novel
      approaches that will be needed to combat PD in HIV afflicted parts of the world
      are suggested.

PMID- 15510942
TI  - Bacterial meningitis in a high HIV prevalence setting in sub-Saharan Africa-
      challenges to a better outcome.
AB  - Bacterial meningitis remains an important cause of mortality and morbidity
      worldwide. Approaches to reducing the incidence include the deployment of
      effective anti-retroviral therapy in areas where HIV co-infection is common,
      vaccination, and prophylactic antibiotic therapy. Health education, improved
      diagnostic speed and capacity, and ensuring appropriate antibiotic therapy may
      improve outcome amongst patients presenting with bacterial meningitis.

PMID- 15510943
TI  - Other bacteria and HIV disease.
AB  - HIV-infected individuals are predisposed to infection with bacteria, in
      particular Streptococcus pneumoniae and non-typhi Salmonella. Other bacteria also
      complicate HIV disease, either because they are inherently pathogenic-
      Staphylococcus aureus, Enterobacteraciae, bacterial agents of enteritis--or they
      take advantage of advanced immunosuppression--Rhodococcus spp, Nocardia spp. An
      understanding of the role of bacteria is essential to the care of HIV-infected
      patients.

PMID- 15510944
TI  - Prevalence of wheeze and self-reported asthma and asthma care in an urban and
      rural area of Tanzania and Cameroon.
AB  - We investigated the prevalence of wheeze, self-reported asthma, and asthma care
      via four cross-sectional surveys among adults and children (5-15 years) in urban
      and rural populations from Tanzania and Cameroon. Age-standardized prevalence of
      current wheeze (in the previous year) was 2.2% to 5.0% in adults and 1.9% to 5.2%
      in children in Tanzania, and 1.3% to 2.5% (adults) and 0.8% to 5.4% (children) in
      Cameroon. There were no consistent patterns of urban:rural prevalence. Peak flow
      rates varied with age, peaking at 25-34 years, and were higher in urban areas
      (age adjusted difference 22-70 L/min) and in the Tanzania populations. Awareness
      (83%-86% versus 52%-58%) and treatment (43%-71% versus 30%-44%) of asthma was
      higher among those with current wheeze in rural areas. Use of inhaled drugs,
      particularly steroids, was rare. Diagnosis by traditional healers (15%) and use
      of traditional remedies (62% of those recalling any treatment) were common only
      among self-reported asthmatic patients in rural Cameroon. Asthma is an
      importantclinical condition in sub-Saharan Africa. There were major gaps in
      clinical care, particularly in urban areas. Sustainable methods for delivering
      accessible and effective asthma care in sub-Saharan Africa are required.

PMID- 15510945
TI  - Retinopathy in Gambian children admitted to hospital with malaria.
AB  - A characteristic retinopathy associated with a poor prognosis has previously been
      described in African children with established cerebral malaria. However,
      relatively little is known about retinal abnormalities in children with severe
      non-cerebral malaria, the group most at risk of developing the cerebral
      complications of this disease. In this study the prevalence, pattern, clinical
      significance and accessibility to clinical examination of this characteristic
      retinopathy are described in 106 Gambian children admitted consecutively to
      hospital with severe malaria, including six with established cerebral malaria.

PMID- 15510946
TI  - The early effects of delayed cord clamping in term infants born to Libyan
      mothers.
AB  - This study was conducted to evaluate the haematological effects of the timing of
      umbilical cord clamping in term infants 24 h after birth in Libya. Mother-infant
      pairs were randomly assigned to early cord clamping (within 10s after delivery)
      or delayed clamping (after the cord stopped pulsating). Maternal haematological
      status was assessed on admission in the delivery room. Infant haematological
      status was evaluated in cord blood and 24 h after birth. Bilirubin concentration
      was assessed at 24 h. 104 mother-infant pairs were randomized to delayed (n=58)
      or early cord clamping (n=46). At baseline the groups had similar demographic and
      biomedical characteristics, except for a difference in maternal haemoglobin,
      which was significantly higher in the early clamping group (11.7 g/dL, SD 1.3
      g/dL versus 10.9 g/dL, SD 1.6 g/dL; P=0.0035). Twenty-four hours after delivery
      the mean infant haemoglobin level was significantly higher in the delayed
      clamping group (18.5 g/dL versus 17.1 g/dL; P=0.0005). No significant differences
      were found in clinical jaundice or plethora. Surprisingly, blood analysis showed
      that two babies in the early clamping group had total serum bilirubin levels (>
      15 mg/dL) that necessitated phototherapy. There were no babies in the late
      clamping group who required phototherapy. Three infants in the delayed clamping
      group had polycythaemia without symptoms, for which no partial exchange
      transfusion was necessary. Delaying cord clamping until the pulsations stop
      increases the red cell mass in term infants. It is a safe, simple and low cost
      delivery procedure that should be incorporated in integrated programmes aimed at
      reducing iron deficiency anaemia in infants in developing countries.

PMID- 15510947
TI  - Perception of severity of acute respiratory tract infections and diarrhoea in
      children under the age of five in rural India: utilization pattern of health
      services.
AB  - A cross-sectional survey of 970 children under the age of 5 in 870 households
      showed a biweekly incidence of acute respiratory tract infections (ARIs) and
      diarrhoea of 9 and 8.7%, respectively. Ninety per cent of the mothers,
      irrespective of their educational status, could identify correctly the severe
      forms of the illness. When perceived as severe the majority (75%) of them went to
      unqualified indigenous practitioners and only when perceived as mild did they use
      the government services. This shows that the user preferences for acute
      healthcare services vary with their perception of the illness and unqualified
      practitioners are the main source of healthcare providers especially in the rural
      areas.

PMID- 15510948
TI  - The brain smear, a rapid affordable intraoperative diagnostic technique for brain
      tumours appropriate for Africa.
AB  - Accurate preoperative and intraoperative diagnosis is important in neurosurgery.
      The most common method of intraoperative diagnosis is the frozen section which
      relies on trained personnel and regular supply of electricity or gas, both of
      which are in short supply in sub-Saharan Africa. The smear technique provides a
      cheap alternative without the need for extra personnel. This method can be easily
      learnt and provides an alternative to the frozen section with reasonable
      diagnostic accuracy. It is hoped that the method can be introduced in areas where
      intraoperative diagnosis is required for brain tumours and the frozen section is
      not available.

PMID- 15510949
TI  - Transfontanelle ultrasonography: an invaluable tool in the assessment of the
      infant brain.
AB  - Transfontanelle (cranial) ultrasonography was carried out in 98 Nigerian infants
      over a period of 5 years. Of the infants, 38 (38.8%) had hydrocephalus from
      various causes while 26 (25.5%) had congenital anomalies. As ultrasound equipment
      is becoming a more readily available and affordable tool in the developing
      countries, it should become much easier for medical staff in these countries to
      arrive at the correct diagnosis of intracranial diseases in infants.

PMID- 15510950
TI  - Cold saline enema in priapism--a useful tool for underprivileged.
AB  - Priapism, prolonged painful erection of the penis, is a urological emergency.
      Untreated, the patient can end up with impotence. Various methods have been
      described for its treatment but the initial management remains conservative. This
      study presents our experience with the use of sedation followed by an ice-cold
      saline enema in the management of priapism.

PMID- 15510951
TI  - Simplifying the feeding tube connection to the draining urinary bag.

PMID- 15510953
TI  - Rapid diagnosis of bacterial meningitis using nitrite patch testing.
AB  - Urine reagent strips have been used to test cerebrospinal fluid (CSF) in areas
      where laboratory facilities are unavailable. Protein, glucose and leukocyte
      esterase patches have been shown to be useful in this context. We propose that
      the nitrite patch also has a contribution to make: it could provide clinically
      useful information, at no extra cost. We tested CSF samples from 200 children
      with suspected meningitis. In a pragmatic approach chosen to reflect the clinical
      dilemma of whether or not to use parenteral antibiotics, the final laboratory
      diagnosis was dichotomized into either 'bacterial meningitis' or 'not bacterial
      meningitis'. These diagnostic categories were compared with nitrite patch
      results, which were either positive or negative. Nitrite patch testing of all
      CSF, clear CSF and bloody CSF gave positive likelihood ratios of 49, 'infinity'
      and 5.8, respectively.

PMID- 15510952
TI  - Epilepsy in a remote area of southern Sudan.

PMID- 15510954
TI  - A comparative study of simple closure versus resection with end-to-side
      ileotransverse anastomosis in non-traumatic terminal ileal perforation in those
      with and without enteric fever.

PMID- 15510955
TI  - The role of eyelash dyes in allergic eye diseases.
AB  - A case-control study was carried out on 544 patients who attended our out-patient
      eye clinic from 1998 to 2002 to determine the role of eyelash dye in allergic eye
      diseases. There were 272 cases who had allergic eye disease and 272 controls who
      were patients with no allergic eye disease. The results showed that 51.8% of all
      patients used eyelash dyes, 70.8% of whom used homemade dyes. Atotal of 82.6% of
      patients reported the worsening of the eye condition after starting the use of
      eyelash dyes. Of the 272 cases, 63.2% used eyelash dyes; in the control group,
      40.4% used eyelash dyes. This was a statistically significant difference. It was
      concluded that eyelash dyes can be one of the major precipitating/aggravating
      factors in allergic eye diseases.

PMID- 15510956
TI  - Assessing prescribing practice in church-owned primary healthcare (PHC)
      institutions in Tanzania: a pilot study.
AB  - A retrospective survey of prescribing patterns in 10 church-owned primary
      healthcare (PHC) institutions in Dar es Salaam region, Tanzania, was carried out
      by trained research assistants in order to assess the prescribing practices of
      healthcare providers in these institutions. From a total of 15,000 prescriptions,
      600 were recorded randomly from patient registers retrospectively. This work was
      carried out between April to September 1996. Each prescription was recorded using
      World Health Organization Action Programme on Essential Drugs (WHO/DAP) forms and
      analysed manually. The average number of drugs per prescription was 2.9; the
      percentage encounters for injections and antibiotics was 38 and 71, respectively.
      Ninety-four per cent of all drugs were prescribed according to the essential drug
      list of Tanzania.

PMID- 15510957
TI  - Non-invasive ventilation in the management of acute respiratory failure in
      Pakistan.
AB  - Data were collected from hospital records on all patients who received non
      invasive ventilation (NIV) during the period 1999-2000. Patients were treated
      with NIV if they had type I or type II respiratory failure or if they had
      respiratory distress with a respiratory rate above 30/min. A total of 68 patients
      (35 males) were studied. NIV was applied using a Respironics Bi-PAP device mostly
      on a high-dependency unit (HDU). A successful outcome with NIV was achieved in
      70% (26/37) of patients with type II failure, 65% (11/17) patients with type I
      failure and 64% (9/14) patients with respiratory distress. Of the 16 patients
      considered to be inappropriate for invasive ventilation on admission, eight were
      treated successfully with NIV. NIV can be applied successfully in developing
      countries.

PMID- 15510958
TI  - Tetanus: an analysis of the prognosticating factors of cases seen in a tertiary
      hospital in a developing African country between 1990 and 2000.
AB  - This is an analysis of the effects of prognosticating factors on the outcome of a
      case series of 66 patients with tetanus, presenting between 1990 and 2000. The
      mortality rate was 26.2% with a fatality rate of 16.2% for those under 40 years
      of age. This increased to 75% for those patients above 70 years of age. The
      socioeconomic status, immunization status, the incubation period, and age of the
      patient together with the severity of the spasms, duration of hospital stay, type
      of treatment received and time of onset were found to affect the outcome of the
      patients.

PMID- 15510959
TI  - Acute pyogenic iliopsoas abscess in children in Nepal.
AB  - We describe a prospective study of twenty-four cases of acute pyogenic abscess of
      the iliopsoas in children treated conservatively and operatively. Eight patients
      were managed conservatively with antibiotics alone while sixteen others were
      managed operatively by open drainage. All made a complete recovery.

PMID- 15510960
TI  - Compressive peroneal neuropathy during harvesting season in Indian farmers.
AB  - Thirty patients (34 limbs) with compressive peroneal neuropathy induced by
      prolonged squatting of more than 5 h during harvesting season were treated
      conservatively and followed-up to an average of 28.2 months. A marked
      preponderance of involvement of the left side was noticed. We attribute this to
      the intermittent extension of the right lower limb habitually used by Indian
      farmers to propel themselves forwards while squatting during harvesting. All but
      two lesions recovered fully within 3 to 9 weeks: one patient took 16 and another
      20 weeks. We recommend non-operative treatment for this benign lesion.

PMID- 15510961
TI  - Abdominal tuberculosis presenting as a massive ovarian cyst.

PMID- 15510962
TI  - Visceral leishmaniasis in a non-endemic area of India.
AB  - The study included 57 patients with visceral leishmaniasis. The average duration
      of symptoms was 3.8 +/- 3.55 months and pancytopenia was the commonest
      haematological abnormality. The parasite load directly correlated with the degree
      of anaemia at presentation (P=0.03). Splenic regression took 9.58 +/- 4.5 days
      and haematological parameters recovered in 14.5 +/- 9.07 days. There were five
      deaths over the five-year study duration. Leishmaniasis was not the first
      diagnosis in 14 patients, of whom eight were residents of non-endemic regions.
      Diagnosis was achieved in 13.5 days in these patients, compared to 4.5 days in
      patients where leishmaniasis was suspected at the outset.

PMID- 15510963
TI  - Seasonality and antimicrobial resistance pattern of Vibrio cholerae in a tertiary
      care hospital of North India.
AB  - We retrospectively analysed the seasonal distribution of cholera and the
      antimicrobial resistance pattern of Vibrio cholerae isolates over a 5-year period
      from January 1998 to December 2002. Of 3213 stool specimens processed from 3213
      patients with acute watery diarrhoea during this period, 431 samples (13.4%) were
      found positive for V. cholerae. There were 423 V. cholerae O1 biotype E1 Tor, 2
      V. cholerae O139 and six isolates of non-O1 non-O139. The highest number of
      cholera cases occurred in May-June followed by July-August. Cases started
      appearing in April for all years except in the year 2002 when three cases
      occurred in the first week of March. A large number (90.25% strains) were
      resistant to at least one antibiotic.

PMID- 15510964
TI  - Tropical vaginal hydroceles in India: are they filarial in origin?

PMID- 15510965
TI  - Seasonality and species of Vibrio cholerae in Karachi, Pakistan.

PMID- 15510966
TI  - Lipid abnormalities among type 2 diabetes mellitus patients: our experience in
      Ilorin, Nigeria.

PMID- 15510967
TI  - Ectopic pregnancy after sterilization.

PMID- 15510968
TI  - Ocular cysticercosis--a profile.

PMID- 15510969
TI  - The use of epidemiological data in formulary development for eye care in South
      Africa.

PMID- 15510970
TI  - Time management in the operating theatre in developing countries.

PMID- 15510971
TI  - Keeping up with our neighbors.

PMID- 15510972
TI  - Pediatric choking.
AB  - Choking episodes and foreign body aspiration can be life threatening or result in
      significant morbidity. Choking continues to be a direct cause of death among
      children, most commonly occurring between the ages of one and four years. Various
      strategies have been used to decrease choking risks and prevent adverse outcomes.
      These have included alterations in product design and public education campaigns.
      Although education has been partially successful, primary care physicians can
      play a critical role in increasing education efforts during each well child
      office visit through anticipatory guidance of choking risks. Management of a
      choking child often involves collaborative efforts from the primary care
      physician, emergency room physician, otolaryngologist, pulmonologist, and
      radiologist. The purpose of this brief review is to provide an overview of the
      epidemiology and pathophysiology of choking and foreign body aspiration in
      children and to highlight important aspects of prevention and patient education.

PMID- 15510973
TI  - The social impact of medicine--chapter 23.
AB  - This paper, an overview of medical history, is based on a course I taught at the
      University of Delaware's Academy of Life Long Learning, "Medicine, the Old and
      the New." It will not be a chronology of medical events and discoveries, but a
      discussion of the social aspects of medicine, how medicine affected the everyday
      lives of people, from the religion-based medicine of antiquity to the super
      scientific medicine of today. This paper is a compilation of other historical
      papers including, but not limited to, those listed in the accompanying
      bibliography. It is not an original paper. This paper will consist of 25
      chapters. Dr. Peter V. Rocca, Editor-in-Chief of the Delaware Medical Journal
      (DMJ), is planning to publish one chapter in each successive issue of the DMJ.

PMID- 15510974
TI  - Peripheral neuropathy: a factor in accidents and falls.

PMID- 15510975
TI  - Understanding the pathobiology of chemotherapy-induced nausea and vomiting.
      Providing a basis for therapeutic progress.
AB  - Improved understanding of the physiologic and neuropharmacologic mechanisms
      underlying chemotherapy-induced nausea and vomiting (CINV) has driven significant
      progress in the treatment of CINV over the past 2 decades. Recognition of the
      role of neurotransmitters and their receptors in the process of CINV has been
      central to this progress. Initial attention focused on dopamine, then on
      serotonin, and most recently on substance P, which has yielded a useful new class
      of antiemetic medications known as selective neurokinin-1 receptor antagonists.
      Preclinical studies of these neurokinin-1 receptor antagonists suggested that
      they would demonstrate broad antiemetic activity in acute emesis, demonstrate
      activity against cisplatin-induced delayed emesis, be well tolerated, and
      contribute to enhanced efficacy when used in combination with other classes of
      antiemetics. These suggestions appear to have been largely borne out in clinical
      trials. Pharmacogenomics may offer a means to further extend and apply our
      understanding of CINV by enabling more selective targeting of antiemetic
      therapies. To date, the application of pharmacogenomics to CINV has focused on
      variations in the metabolism of serotonin receptor antagonists by CYP 450
      genotype and variations in the 5-HT3 receptor gene itself.

PMID- 15510976
TI  - New developments in the management of chemotherapy-induced emesis: do they impact
      on existing guidelines?
AB  - Guidelines for the management of chemotherapy-induced emesis are necessary to
      help clinicians match the emetogenicity of antineoplastic agents with the
      abundance of antiemetic agents now available. Numerous guidelines for antiemetic
      therapy currently exist, but compliance with them is inconsistent, in part
      because optimal antiemetic protection is not yet possible, even with the best
      guidelines. For this reason, guidelines must be dynamic and evolve as knowledge
      increases. Revision of antiemetic guidelines should be prompted by changes in
      general principles of treatment, not changes in specific details. Recent
      recognition of the unique benefits of incorporating selective neurokinin-1
      receptor antagonists into regimens for the prevention of nausea and vomiting
      caused by highly emetogenic chemotherapy, particularly in delayed emesis,
      justifies modification of existing antiemetic guidelines.

PMID- 15510977
TI  - How does DNA methylation mark the fate of cells?
AB  - Since every cell of a multicellular organism contains the same genome, it is
      intriguing to understand why genetically homogenous cells are different from each
      other and what controls this. Several observations indicate that DNA methylation
      has an essential regulatory function in mammalian development, which is to
      establish the correct pattern of gene expression, and that DNA methylation
      pattern is tightly correlated with chromatin structure. Various physiological
      processes are controlled by specific DNA methylation patterns including genomic
      imprinting, inactivation of the X chromosome, regulation of tissue-specific gene
      expression and repression of transposons. Moreover, aberrant methylation could
      confer a selective advantage to cells, leading to cancerous growth. In this
      review we focus on the epigenetic molecular mechanisms during normal development
      and discuss how DNA methylation could affect the expression of genes leading to
      cancer transformation.

PMID- 15510978
TI  - Neoadjuvant therapy of rectal cancer new treatment perspectives.
AB  - During the past two decades, significant advances have been made in the
      management of patients with rectal cancer. A number of clinical studies have
      demonstrated the efficacy of preoperative chemoradiation therapy with 5
      fluorouracil (5-FU)-based regimens in decreasing local recurrences and improving
      survival and the likelihood of sphincter preservation. Although 5-FU has been the
      standard drug used in combination with radiation therapy for many years, new
      effective drugs including capecitabine, raltitrexed, irinotecan and oxaliplatin
      have been recently investigated in combination with radiation therapy in the
      preoperative setting. In addition, novel targeted biological agents including
      epidermal growth factor receptor inhibitors and vascular endothelial growth
      factor inhibitors have been shown to enhance the antitumor effect of both
      radiation and chemotherapy and are currently being explored in initial clinical
      trials. In the present review we summarize the results of adjuvant therapy. In
      addition, we will discuss the recently reported phase I-II trials with new drug
      plus radiation combinations in the preoperative treatment of patients with rectal
      cancer.

PMID- 15510979
TI  - T1-T2 breast cancer with four or more positive axillary lymph nodes: adjuvant
      locoregional radiotherapy with high-dose or standard-dose chemotherapy. Results
      of an observational study.
AB  - AIM AND BACKGROUND: The aim of this study was to investigate the efficacy of
      postoperative locoregional radiotherapy in patients with T1-T2 breast cancer and
      four or more positive axillary lymph nodes submitted to mastectomy or breast
      conserving surgery followed by standard-dose or high-dose adjuvant chemotherapy.
      The incidence of locoregional relapses and the survival correlated with the
      number of positive nodes were recorded for each treatment arm. PATIENTS AND
      METHODS: From August 1992 to August 1999 86 breast cancer patients (median age,
      54 years, T1-T2, N+ > or = 4) submitted to surgery were treated. Sixty-three
      patients received standard-dose chemotherapy while 23 patients with 10 or more
      positive nodes received high-dose chemotherapy. After four courses of standard
      dose anthracycline-based chemotherapy peripheral blood stem cells were mobilized
      with cyclophosphamide (7 g/m2) and G-CSF (10-16 microg/kg/day/sc). High-dose
      chemotherapy consisted of etoposide 1000 mg/m2, thiotepa 500 mg/m2 and
      carboplatin 800 mg/m2. Hormone receptor-positive patients underwent hormone
      therapy. Following chemotherapy all 86 patients were given conventional
      radiotherapy to the breast or the chest wall and the supraclavicular fossa. The
      high-dose subgroup received radiotherapy to the internal mammary nodes +/-
      axilla. RESULTS: The median follow-up from the start of radiotherapy was 36.5
      months. Locoregional relapses occurred in nine patients (10.4%); in four of them
      they were isolated (4.6%). Local relapses were four (4.6%) and regional relapses
      six (6.9%). Twenty-five patients (29%) had distant metastases. The five-year and
      eight-year overall actuarial survival rates were 82.6% +/- 4.8 and 60.1% +/- 8.8,
      respectively. No statistical differences were found when the number of positive
      nodes or the type of treatment of N+ 10 patients was included in the analysis.
      CONCLUSIONS: Breast cancer patients with four or more positive axillary lymph
      nodes are at high risk of developing locoregional and distant relapses. The
      results reported here demonstrate the efficacy of radiotherapy in the reduction
      of locoregional failure; no differences in survival and locoregional control in
      relation to treatment arm and number of positive nodes were found.

PMID- 15510980
TI  - Effects of interferon-alpha-2a on Th3 cytokine response in multiple myeloma
      patients.
AB  - AIMS AND BACKGROUND: Multiple myeloma cells increase Th3 cytokine response by
      secreting TGF-beta, which causes defective Th1 and Th2 cytokine responses.
      Therefore, a significant suppression of the immune system is seen in multiple
      myeloma. Interferon-alpha (IFN-alpha) is used in the treatment of multiple
      myeloma due to its immunomodulatory and anti-tumoral effects. We attempted to
      define the characteristics of immune cytokine responses and the effects of IFN
      alpha-2a on the immune response in multiple myeloma. METHODS: Fifteen patients
      with multiple myeloma and 15 healthy controls were enrolled. IFN-alpha-2a, 3
      million units/day x 3 times/week, was administered subcutaneously to the patients
      for 2 weeks. Cytokines (TGF-beta, IL-1, IL-2, IL-4, IL-10, IFN-gamma) were
      assessed by the ELISA method in sera of the patients in pretreatment and
      posttreatment periods and in the sera of the controls. RESULTS: IL-2 and IL-4
      levels in patients, before IFN-alpha-2a, were lower than the controls, whereas
      TGF-beta levels were higher than the controls. In other words, Th3 cytokine
      response was increased and Th1 and Th2 cytokine responses were decreased in
      patients. A short course of IFN-alpha-2a increased IL-2 levels. CONCLUSIONS:
      These findings suggest IFN-alpha-2a may enhance nonTh3 cytokine responses in
      multiple myeloma patients.

PMID- 15510981
TI  - Safety and efficacy of enoxaparin treatment in venous thromboembolic disease
      during acute leukemia.
AB  - BACKGROUND: Venous thromboembolism (VTE) is a quite common complication in acute
      leukemia, although its real incidence is unknown. The best treatment of this
      complication is still a matter of debate due to the very high risk of hemorrhage
      in this group of patients. PATIENTS AND METHODS: From December 2000 to December
      2002 four Caucasian patients with acute leukemia developed VTE complications. The
      patients were three men and one woman, mean age 55.7 years (range, 27-77). Two
      patients with acute lymphoid leukemia (L1 and L2 according to the FAB
      classification) developed deep venous thrombosis during the administration of
      chemotherapy; one patient with acute myeloid leukemia (AML, M2 according to the
      FAB classification) had pulmonary thromboembolism at diagnosis, while another AML
      patient (M4 according to FAB) showed deep venous thrombosis as the first symptom
      of leukemia. The clinical diagnosis of symptomatic VTE was confirmed by objective
      imaging procedures including lower limb venous color Doppler imaging in all cases
      and a ventilation-perfusion lung scan in one case. All patients were treated with
      enoxaparin 100 IU/kg subcutaneously twice daily for one month, followed by 150
      IU/kg once daily for at least five months. When the platelet count was below
      20,000 x 10(9)/L, the dose was reduced by 50%. RESULTS: During antithrombotic
      treatment neither VTE recurrences nor hemorrhagic complications or heparin
      induced thrombocytopenia occurred. The platelet count at the beginning of
      enoxaparin treatment was very low (mean, 55,750 x 109/L; range, 12,000-121,000 x
      10(9)/L) and treatment did not affect platelet recovery. CONCLUSIONS: Enoxaparin
      proved to be efficacious and safe in the management of deep venous thrombosis
      with or without pulmonary embolism in patients affected by acute leukemia.
      Enoxaparin cured acute venous thrombosis, prevented recurrences and did not cause
      any hemorrhagic complications despite prolonged severe thrombocytopenia.

PMID- 15510982
TI  - Comparison of clinical outcomes of different erythropoietin usage strategies.
AB  - AIM: There is no comprehensive study that compares the different usage strategies
      of recombinant human erythropoietin (rHuEPO) in platinum-induced anemia. In order
      to clarify this issue, we conducted a prospective clinical study. MATERIAL AND
      METHODS: Seventy-seven patients were studied in three main groups. Group 1 (n =
      17) consisted of cancer patients without anemia. These patients received rHuEPO
      starting from the first chemotherapy cycle. Group 2 (n = 26) consisted of
      patients whose hemoglobin (Hb) values decreased by at least 1 g/dL after the
      first cycle of chemotherapy. Group 3 (n = 34) consisted of patients whose Hb
      values dropped below 10.5 g/dL after the second chemotherapy cycle. Groups 2 and
      3 were each divided into two subgroups. In groups 1, 2A and 3A rHuEPO (5000 U/day
      subcutaneously three times a week) treatment was continued until three weeks
      after the completion of chemotherapy. In groups 2B and 3B, rHuEPO was given for
      12 weeks only. RESULTS: There were no prominent differences between the Hb values
      of these groups throughout the chemotherapy cycles. Transfusion rates and the
      number of patients who became anemic were also not different between groups.
      CONCLUSION: No rHuEPO usage strategies are superior to others in terms of Hb
      levels and transfusion requirements. The decision as to when rHuEPO is to be
      added to platinum-containing therapy should be tailored to the health conditions
      of individual patients.

PMID- 15510983
TI  - Clinical experience with psychological aspects in pediatric patients amputated
      for malignancies.
AB  - AIMS AND BACKGROUND: Amputation surgery in pediatric patients suffering from
      malignant tumors is less common than in the past, but has a great emotional
      impact on patients and their families as well as on the medical team. Studies
      addressing the psychological aspects of limb amputation in childhood cancer are
      still relatively limited, and the results have sometimes been contradictory.
      METHODS: At the Pediatric Oncology Unit of the Istituto Nazionale Tumori of Milan
      psychological support was provided to candidates for amputation and their
      families, involving medical oncologists, a clinical psychologist, and social
      assistants. Twenty-two patients were analyzed and 16 underwent mutilating
      surgery. RESULTS: Different emotional reactions were observed. Surgery proved to
      be easier to accept when the tumor caused pain and functional loss. Specialist
      medical psychological support was needed in case of defense mechanisms (eg,
      splitting and projection) and depressive reactions evolving into isolation or
      intolerance. CONCLUSIONS: The reported experience could be helpful in providing
      adequate support to children with tumors requiring mutilating surgery.

PMID- 15510984
TI  - Preoperative evaluation of patients submitted to pneumonectomy for lung
      carcinoma: role of exercise testing.
AB  - The aim of the present investigation was to evaluate which parameters of
      preoperative spirometry, arterial blood gas, radionuclide lung scanning and
      cardiopulmonary exercise test are the best predictor of postoperative morbidity
      and mortality in patients submitted to pneumonectomy. The study was conducted in
      150 patients (mean age, 57.1). Forty-four patients (29.3%) had postoperative
      complications. Four patients (2.7%) died within one month of the pneumonectomy.
      Patients with complications had significantly lower ppoFEV1 as percentage of
      predicted and lower VO2 max, and those who died also had a significant decrease
      in PaO2 during exercise. Moreover, among patients with obstructive pulmonary
      disease (FEV1<70% of predicted), we found a significantly higher percentage
      predicted residual volume and a significantly lower VO2 max in complicated
      patients. The present data support the suggestion that exercise testing could be
      a useful adjunct in the evaluation of postoperative risk for pneumonectomy,
      especially in patients with obstructive pulmonary disease. In particular,
      patients with VO2 max <50% of predicted should be considered at high risk of
      morbidity from cardiopulmonary causes.

PMID- 15510985
TI  - Gynecomastia due to hormone therapy for advanced prostate cancer: a report of ten
      surgically treated cases and a review of treatment options.
AB  - AIMS AND BACKGROUND: Gynecomastia is an abnormal increase in the volume of the
      male breast that is generally considered to be due to an increased
      estrogen/androgen ratio. Pathological causes of gynecomastia include organic
      diseases and therapy, such as the administration of estrogens and antiandrogens,
      which alter the ratio of circulating hormones. Hormone therapy for prostate
      cancer is generally well tolerated but often accompanied by the occurrence of
      gynecomastia and breast pain or tenderness. The increased use of antiandrogens as
      monotherapy is leading to an increase in the number of patients affected by
      gynecomastia. Treatments are available to alleviate or prevent the development of
      gynecomastia, including medical treatment with antiestrogens and aromatase
      inhibitors. Alternatively, mastectomy with excision of the gland, liposuction or
      an association of the two techniques have proved to be effective. Radiation
      therapy may provide effective relief from the breast pain associated with
      gynecomastia. In this paper we show the good results of mastectomy performed with
      a lower semicircular periareolar incision in men suffering from gynecomastia due
      to antiandrogen therapy for inoperable prostate cancer. In addition, we present a
      review of the various techniques used for the treatment of gynecomastia. METHODS
      AND STUDY DESIGN: During the period from September 1998 to May 2001, 10 patients
      receiving hormone treatment for metastatic or inoperable prostatic cancer were
      selected for the study if they had breast pain and bilateral gynecomastia. Five
      of these patients had been offered prophylactic radiotherapy before treatment but
      refused, while the remaining five patients had refused radiotherapy after hormone
      treatment. These patients were therefore given the option of surgical treatment.
      Before surgery all patients underwent clinical and ultrasound examination of the
      breast. All surgical samples were examined histopathologically. During follow-up
      clinical examinations were carried out one week, one month, six months, one year
      and two years after surgery. RESULTS: The results were satisfactory in all
      patients especially from an aesthetic point of view. Moreover, breast pain
      disappeared about one week after surgery. After a follow-up of 6-36 months
      (average, 22.8 months) no recurrences were observed. Only a few immediate
      postoperative complications were recorded (hematoma in one case and seroma in
      another). Histological examination of the excised glands showed fibrosclerotic
      tissue and a small amount of fat. CONCLUSION: Surgical liposuction can be
      considered an effective treatment for gynecomastia, in particular in the very
      early stages because the breast becomes irreversibly fibrous as the disease
      progresses. This surgical technique is simple and effective and is therefore to
      be considered favorable, especially because of the very short hospitalization and
      the absence of complications.

PMID- 15510986
TI  - Post-traumatic glioma. Report of four cases and review of the literature.
AB  - AIMS AND BACKGROUND: To add a further contribution to the literature supporting
      the relationship between previous head trauma and development of glioma. METHODS:
      We report on four patients who developed brain gliomas in the scar of an old
      brain injury. RESULTS: All cases fulfilled the widely established criteria for
      brain tumors of traumatic origin. In all of our cases there was radiological
      evidence of absence of tumor at the time of the injury. CONCLUSIONS: We believe
      that in specific cases it is reasonable to acknowledge an etiological association
      between a severe head trauma and the development of a glioma. This assumption is
      further sustained if there is radiological and surgical documentation of the
      absence of neoplasia at the moment of the trauma.

PMID- 15510987
TI  - Prolonged remission in a patient with transitional cell carcinoma of the bladder
      developing brain metastases after systemic chemotherapy: a case report.
AB  - We report a case of an excellent response to M-VAC chemotherapy in a patient with
      pulmonary metastases from transitional cell carcinoma of the bladder. He
      subsequently presented with acute neurological symptoms seven weeks after the
      completion of chemotherapy. Computed tomography of the brain revealed a solitary
      24 mm x 26 mm lesion in the frontal lobe. The brain metastasis was resected. The
      patient was closely followed for disease progression and showed no evidence of
      disease up to 42 months after surgery. The presentation and treatment policy are
      discussed. This case suggests that long-term remission may be obtained after
      surgical resection of a single brain metastasis in patients with disseminated
      urothelial cancer who completely responded to systemic chemotherapy.

PMID- 15510988
TI  - Leydig cell tumor of the testis. New cases and review of the current literature.
AB  - Leydig cell tumors are the most frequent non-germ cell tumors of the testis,
      accounting for 1-3% of all testicular tumors. They present most commonly as a
      testicular mass or with endocrine symptoms. We report three new cases of Leydig
      cell tumors that presented in different forms. The relevant literature is
      reviewed and the management of these tumors is discussed.

PMID- 15510989
TI  - Presentation of malignant pleural mesothelioma with symptomatic brain metastasis:
      report of a case.
AB  - Central nervous system metastases from diffuse malignant pleural mesothelioma are
      rare. Here we describe a patient without known asbestos exposure who presented
      with chest pain, increasing shortness of breath and persistent headache.
      Evaluation found biphasic malignant mesothelioma of the right hemithorax and a
      single brain metastasis confirmed by computed tomography. This represents only
      the second case of a patient with pleural mesothelioma presenting with
      symptomatic central nervous system metastases.

PMID- 15510990
TI  - Hepatic arterial infusion chemotherapy in gastric cancer: a report of four cases
      and analysis of the literature.
AB  - AIMS AND BACKGROUND: Gastric cancer is associated with high mortality. Although
      the liver is a common site of metastases in this tumor, the experience with liver
      directed therapies is limited. METHODS: We report a single-center experience
      involving four patients with liver metastases from gastric cancer treated by
      hepatic arterial infusion (HAI). In addition, we performed a search for reports
      on HAI in gastric cancer metastatic to the liver and used the studies with data
      on survival of individual patients for a pooled analysis. RESULTS: Among three
      valuable patients, one had a complete response, one had stable disease and one
      had progressive disease. The patient with complete response is still alive 41
      months after the diagnosis of liver metastases, while the other patients died 6,
      22 and 31 months after the diagnosis. Objective responses were observed in 48% of
      the 25 patients in the pooled analysis. Objective response and limited hepatic
      involvement were independent predictors of survival in these patients.
      CONCLUSIONS: Although isolated liver involvement in metastatic gastric cancer is
      rare, HAI seems to be similarly effective in these patients as in patients with
      liver metastases from colorectal cancer. The prognosis is significantly better in
      gastric cancer patients who have limited hepatic involvement and attain an
      objective response after HAI.

PMID- 15510991
TI  - Analysis of the reasons for accepting or declining participation in genetic
      research for breast cancer: a hospital-based population study.
AB  - The majority of a hospital-based population accepted to participate in a
      molecular screening project for familial breast cancer, giving their informed
      consent to blood sampling. Only 9.5% of patients declined to sign the consent
      form. Here we report the reasons for refusal and we critically review our
      methodological approach to obtain consent for a blood test for genetic research
      in a clinical setting.

PMID- 15510992
TI  - Meeting report: Breast cancer in the older woman.

PMID- 15510993
TI  - [ASCO Annual Meeting 2004, New Orleans. Tumoral angiogenesis and inhibition of
      VEGF: clinical implications].

PMID- 15510994
TI  - [ASCO Annual Meeting 2004, New Orleans. Therapeutic options in colorectal
      cancer].

PMID- 15510995
TI  - [Chemotherapy for advanced non-small-cell lung cancer. From the exclusive use of
      "P" to a quantitative probabilistic interpretation of meta-analytic data].

PMID- 15510996
TI  - Liposomes as adjuvant for anti-mycobacterial vaccine development.
AB  - Mycobacteria are intracellular pathogens that invade and reside inside the
      macrophages. Recent advances in controlled delivery systems for vaccines such as
      liposomes have sparked a renewed interest in their potential application for the
      prevention of mycobacterial infections. The versatility of liposomes in the
      incorporation of hydrophilic/hydrophobic components, their non-toxic nature,
      biodegradability, biocompatibility, adjuvanticity, induction of cellular
      immunity, property of sustained release and prompt uptake by macrophages, makes
      them attractive candidates for the delivery of antigens. This review focuses on
      liposome research in the area of mycobacterial diseases and highlights how the
      various mycobacterial components may be exploited as powerful antigens with
      liposomes as adjuvants.

PMID- 15510997
TI  - Influence of malaria parasite (P. vivax) on erythrocyte aggregation: a study
      based on dynamic imaging and analysis.
AB  - Malaria due to P. vivax (PV) is prevalent in many countries. The present work is
      aimed to determine the cell-cell interaction through formation of aggregates
      under dynamic conditions. Blood samples are obtained from patients (n=11)
      suffering from PV malaria, and the normal subjects (n=10) in test tubes
      containing citrate phosphate dextrose (10:1.4), as an anticoagulant. The
      signature analysis of infected erythrocytes shows significant alterations in
      their shape and membrane. For aggregation analysis, erythrocyte suspension in
      plasma at hematocrit 5%, was placed in a glass chamber and mounted vertically on
      the stage of the video-microscope system. The aggregate images thus acquired show
      erythrocytes adhering with each other to form mash-like structures. With increase
      in parasitaemia, the erythrocytes show hyper-aggregation compared to that of
      normal cells. By processing of the sequence of recorded images during
      sedimentation, the various aggregation parameters are obtained. These parameters
      show that the formed aggregates are compact which produce distinct changes in
      sedimentation pattern with significantly higher sedimentation velocity compared
      to that in healthy blood samples. These changes in malaria could partly be
      responsible for alteration in blood flow through microcirculatory system.

PMID- 15510998
TI  - Effect of fly ash inhalation on biochemical and histomorphological changes in rat
      lungs.
AB  - Effect of respirable fly ash particles inhalation on lungs of rats was
      investigated by exposing them to respirable aerosols of size classified power
      plant fly ash at average concentrations of up to 14.4 +/- 1.77 mg/m3 for 4 hr/day
      for 28 consecutive days. A remarkable increase was found in blood eosinophil
      counts of fly ash exposed animals. Biochemical indicators of pulmonary damage
      viz. lactate dehydrogenase (cytoplasmic enzyme used as a measure of cell injury),
      gamma-glutamyl transferase (Clara cell damage) and alkaline phosphatase
      (potential measure of Type 11 cell secretions) in broncho alveolar lavage fluid
      (BALF) of fly ash exposed group showed significant elevation. Clumping of fly ash
      particles in the lungs was observed as evidenced by fly ash ladened macrophage
      accumulation in the alveolar region. The results suggest a damage, local
      inflammation and remodelling of lung as indicated by hypertrophy and hyperplasia.
      These changes reflect the toxic effects of the fly ash inhalation.

PMID- 15510999
TI  - Biokinetics of 65Zn in liver and whole body and its bio-distribution in nickel
      treated protein deficient rats.
AB  - This study was designed to determine the effect of nickel treatment on biological
      half-lives of 65Zn in whole body and liver as well as on distribution of 65Zn in
      different organs of protein deficient rats. Nickel sulfate at a dose level of
      800mg/l in drinking water was administrated to normal control as well as to
      protein deficient rats for 8 weeks. A significant increase was found in fast and
      slow components of biological half lives of 65Zn in whole body and only fast
      component in liver of protein deficient rats. Interestingly, slow component in
      whole body and fast component in liver of nickel treated protein deficient rats
      were not different from normal controls though they were significantly elevated
      in protein deficient rats. On the other hand, slow component of 65Zn was also not
      altered in nickel treated protein deficient rats, which however, was
      significantly decreased in nickel treated rats. Protein deficiency led to a
      marked elevation in per cent uptake of 65Zn in brain and caused significant
      depression in liver, kidney and intestine. However, uptake of 65Zn in brain
      showed a significant depression in nickel treated rats, whereas the uptake was
      elevated in brain in nickel treated protein deficient rats. In conclusion,
      protein deficient conditions seem to be playing a dominant role in context with
      the distribution of 65Zn in different organs when nickel is administered to
      protein deficient rats. However nickel alone is seen to cause adverse effect on
      the distribution of 65Zn.

PMID- 15511000
TI  - Secretion of metastasis related gangliosides by mouse B16-melanoma in circulation
      in vivo and in culture media in vitro.
AB  - Mouse B16LuF1 melanoma cells of lower metastatic potential to lung were treated
      in vitro with same concentration (50 microM) of gangliosides prepared from plasma
      of mice bearing lung metastasis of B16LuF5, B16LuF9 or B16LuF10 melanoma cell
      lines of increasing metastatic potential to lung (LuF1 < LuF5 < LuF9 < LuF10) and
      injected to normal mice through tail vein. The number of metastatic tumor nodules
      formed in lung increased gradually in mice receiving B16LuF5, B16LuF9 and
      B16LuF10-ganglioside-treated B16LuF1 cells compared to mice receiving B16LuF1
      cells without any ganglioside treatment. Similarly, mouse B16LuF1 melanoma cells
      treated in vitro with 50 microM concentration of gangliosides prepared from spent
      culture media of B16LuF5, B16LuF9 or B16LuF10 cells cultured in vitro were
      injected to normal mice through tail vein. The number of metastatic tumor nodules
      formed in lung increased gradually in mice receiving B16LuF5, B16LuF9 and
      B16LuF10-ganglioside-treated B16LuF1 cells compared to mice receiving B16LuF1
      cells without any ganglioside treatment. The results indicated that metastasis
      associated gangliosides present in plasma and culture media of B16-melanoma of
      increasing metastatic potential to lung enhanced metastatic potential of B16LuF1
      cells. The increasing concentration of metastasis-associated gangliosides present
      in plasma and in culture media of B16-melanoma of increasing metastatic potential
      possibly determined increase in metastatic potential of B16LuF1-melanoma cells.

PMID- 15511001
TI  - Antitumour activity of some plants from Meghalaya and Mizoram against murine
      ascites Dalton's lymphoma.
AB  - Total five plants, three from Mizoram (Dillenia pentagyna, Ageratum conyzoides,
      Blumea lanceolaria) and two from Meghalaya (Potentilla fulgens, Taxus baccata)
      were studied for their antitumour activity against murine ascites Dalton's
      lymphoma (DL) in vivo. Only three plants showed the different magnitude of
      antitumour activity. Out of these three plants, the antitumour activity was
      maximally observed with the methanol extract of the stem bark of D. pentagyna as
      compared to the aqueous extract of the roots of A. conyzoides and aqueous extract
      of the root of P. fulgens. An increase in glutathione levels in Dalton's lymphoma
      cells was observed during tumour growth. Changes in glutathione and protein
      levels were also investigated in the liver and Dalton's lymphoma cells of tumour
      bearing mice following the treatment with the extract of D. pentagyna which
      showed the highest antitumour activity as compared to the other two plant
      extracts. Glutathione in the liver and DL cells of treated tumour-bearing mice
      was found to be decreased. The protein concentration in liver and DL cells
      decreased mainly at 96 hr of treatment. It may be concluded that the natural
      product of D. pentagyna promises to be more active against Dalton's lymphoma than
      others and the decrease in glutathione level may be one of the important steps in
      resulting this antitumour effect.

PMID- 15511002
TI  - Antioxidant effect of Boerhavia diffusa L. in tissues of alloxan induced diabetic
      rats.
AB  - Administration of B. diffusa leaf extract (BLEt; 200 mg/kg) for 4 weeks resulted
      in a significant reduction in thiobarbutric acid reactive substances and
      hydroperoxides, with a significant increase in reduced glutathione, superoxide
      dismutase, catalase, glutathione peroxidase and glutathione--S-transferase in
      liver and kidney of alloxan induced diabetic rats. The results suggest that BLEt
      has remarkable antidiabetic activity and can improve antioxidant status in
      alloxan induced diabetic rats.

PMID- 15511003
TI  - Effect of propolis extract on acute carbon tetrachloride induced hepatotoxicity.
AB  - Ethanolic extract of propolis was administered to rats intoxicated by carbon
      tetrachloride. Administration of bolus dose of CCl4 (1.5 ml/kg, ip) resulted in
      elevation of serum transaminases and serum alkaline phosphatase activities.
      Levels of hepatic lipid peroxidation were significantly increased. On the
      contrary, there was significant decrease in hepatic reduced glutathione level.
      The propolis extract (100 and 200 mg/kg, po) exhibited recoupment in both pre-
      and post-treatment (prophylactic and curative studies) of biochemical changes
      induced by CCl4. The post treatment of 200 mg/kg, po extract showed most
      significant hepatoprotective effect. Histopathological studies showed damage in
      hepatocytes and disturbed chord arrangement after toxicant administration.
      Propolis extract (200 mg/kg, po) was found to be more effective in restoring CCl4
      induced histopathological alterations.

PMID- 15511004
TI  - Modulatory potential of Spirulina fusiformis on testicular phosphatases in Swiss
      albino mice against mercury intoxication.
AB  - Administration of mercuric chloride (HgCl2; 5.0 mg/kg body weight) to male Swiss
      albino-mice resulted in significantly higher levels of testicular acid
      phosphatase (ACP) and alkaline phosphatase (ALP) activities as compared to
      control. In combination group where S. fusiformis (800 mg/kg body weight) was
      given before and after HgCl2 treatment, the mercury induced toxicity reduced in
      terms of decreased levels of ACP and ALP activities in the testis. The animal
      treated with only Spirulina did not show any alteration in ACP and ALP values. It
      is suggested that oral administration of Spirulina can modulate mercury induced
      testicular toxicity.

PMID- 15511005
TI  - Toxicity of Nerium indicum Miller seed extract on bandicoot rat, Bandicota
      bengalensis Gray.
AB  - Crude extract (12.5 ml/kg) of N. indicum seed gave 100% mortality of B.
      bengalensis. Humanness assessment study revealed that this plant orgin chemical
      caused low pain and sufferings to the target pests.

PMID- 15511006
TI  - Histology of vitamin A induced ectopic limbs and normal hind limbs in tadpoles of
      Polypedates maculatus.
AB  - Marked histological similarities were observed between normal and vitamin A
      induced ectopic limb buds of P. maculatus. However, close association of nephric
      tubule and lateral plate mesoderm, as seen in normal hind limb bud does not seem
      to be essential for ectopic limb development. The ectopic limbs tend to develop
      in pairs.

PMID- 15511007
TI  - Evaluation of secondary poisoning of difethialone, a new second-generation
      anticoagulant rodenticide to barn owl, Tyto alba Hartert under captivity.
AB  - Secondary toxcity of difethialone to Barn owl (Tyto alba) has been investigated.
      Difethialone was fed to owls for successive periods of 1 (phase 1), 3 (phase 2)
      and 6 (phase 3) days via-rodenticide dosed rats. The owls survived after the
      treament of rodenticide on phase 1 and phase 2 experiments but they died during
      phase 3 experiment. The results suggest that the difethialone could cause more
      secondary toxicity to owls.

PMID- 15511008
TI  - Enzymatic changes induced by some organophosphorus pesticides in female rats.
AB  - An evaluation of toxic effects of three organophosphorus pesticides viz.
      monocrotophos, methyl parathion and dimethoate given orally daily for 90 days was
      done in terms of enzymatic changes in plasma and liver of female albino rats. A
      significant decrease was observed in the level of esterases in plasma with all
      the three pesticides. The activity of acid and alkaline phosphatases and
      aminotransferases increased significantly in plasma and significantly or
      marginally in liver with these pesticides. The results are thus indicative of the
      cellular toxicity of these organophosphates even after their subchronic
      administration in low doses for a long period.

PMID- 15511009
TI  - Production of solasodine by Solanum laciniatum using plant tissue culture
      technique.
AB  - Leaf and hypocotyl explants of 15 days old aseptically grown seedlings of Solanum
      laciniatum were cultured on MS medium supplemented with NAA (2 mg/l) and kinetin
      (0.5 mg/l) for callus initiation. For maintenance and proliferation of callus MS
      medium supplemented with 2,4-D (1 mg/l) and kinetin (0.5 mg/l) was used. The
      growth of the calli derived from hypocotyls increased with time of incubation and
      remained almost constant after 45 days. The solasodine content in callus culture
      was maximum after 30 days of incubation. Addition of L-arginine in the medium (50
      150 mg/l) increased growth as well as chlorophyll content in the callus culture.
      The solasodine content also increased up to 1.2 to 1.4 times in these cultures.
      High frequency shoot regeneration was obtained in MS medium having BA (4 mg/l)
      and IBA (0.25 mg/l). For shoot multiplication, MS medium having BA (4 mg/l) was
      used. Shoots rooted on the same medium. Organogenesis promoted solasodine
      accumulation in the cultures. Regenerated shoots yielded higher solasodine
      content than undifferentiated as well as organogenic callus. Solasodine contents
      in the regenerated shoots was found to be 10 times higher than the callus culture
      and approached towards the field grown plants. Thin layer chromatography revealed
      the presence of three compounds. The most predominant spot (Rf 0.789)
      corresponded to the reference solasodine.

PMID- 15511010
TI  - Protective effect of vilva juice on glycoconjugate levels in experimentally
      induced constipation in rats.
AB  - Efficacy of vilva, a polyherbal formulation was evaluated in morphine induced
      constipated rats. Vilva juice, at a dose of 1.5 ml/100 g body wt was given orally
      for a period of 7 days. Morphine sulfate was injected to induce constipation on
      8th day, 45 min before the experiments. Protein bound glycoconjungates were
      estimated in intestinal tissue. Altered levels of glycoconjugates were maintained
      at near normalcy when pretreated with vilva juice in morphine induced rats.
      Histological changes were observed in the colon tissue. The damage to crypts of
      Liberkunn in constipated rats were found to be reduced in vilva pretreated rats.
      Vilva, thus, offered significant protection against morphine induced constipation
      by way of augmenting mucus secretion.

PMID- 15511011
TI  - Mini transposon vector mediated foreign gene expression in Mesorhizobium huakuii
      subsp. rengei.
AB  - Among the transposable elements, mini-Tn5 transposon vector has proven to be of
      greater utility for insertion mutagenesis of variety of Gram negative bacteria.
      The mini-Tn5 vector containing promoter less egfp gene and gentamycin resistant
      gene was used for the present study. The transposon vector was introduced to M.
      huakuii from E. coli S17 by conjugation. The conjugants were screened for stable
      expression of egfp both in free-living and in nodules of Astragalus sinicus. The
      result showed that the conjugant #3 showed stable expression of green fluorescent
      both in free-living and bacteroid stage. The visualization of sym plasmid of wild
      strain and conjugants showed that conjugant #3 had a fragmentation of large sized
      plasmid into two but without affecting the nodulating ability. These results
      clearly indicated that mini-Tn5 vectors (Transposon vectors) the best alternate
      tools for plasmid vectors for integration of foreign genes in chromosomal DNA or
      symbiotic plasmid and expression, both in free-living and bacteroid stage of
      Rhizobium.

PMID- 15511012
TI  - Identification of glandular (preputial and clitoral) proteins in house rat
      (Rattus rattus) involved in pheromonal communication.
AB  - Proteins (18-20 kDa) belonging to lipocalin family have been reported to act as
      carriers for ligands binding to pheromones in mouse urine, pig saliva, hamster
      vaginal fluid and human sweat, that are involved in pheromonal communication. As
      the preputial gland is a major pheromonal source, the present study was aimed to
      detect the specific protein bands (around 18-20 kDa) in the preputial and
      clitoral glands of the house rat, R. rattus. The amount of protein was higher in
      preputial gland of the male than that of female (clitoral) gland. A 20 kDa
      protein was noted in male and female glands; however, the intensity of the band
      was much higher in male than in female. In addition, 70, 60, 35 kDa bands,
      identified in male preputial gland, were absent in females. The presence of
      higher concentration of glandular proteins in the male preputial gland suggests
      that male rats may depend more on these glandular proteins for the maintenance of
      reproductive and dominance behaviours. The results further suggest that these
      glandular proteins (20 kDa) may act as a carrier for ligand binding.

PMID- 15511013
TI  - Funding crisis at the Radiation Effects Research Foundation.

PMID- 15511014
TI  - Epidemiological studies of UK test veterans: I. General description.
AB  - This review gives a general account of how and why epidemiological studies of UK
      participants in the nuclear weapons test programme were set up. There is a short
      description of the circumstances in which the tests were planned and executed and
      a discussion of the general considerations involved in designing studies to show
      whether the health of test participants suffered as a result of the tests. The
      companion review article summarises the results of the epidemiological studies.

PMID- 15511015
TI  - Epidemiological studies of UK test veterans: II. Mortality and cancer incidence.
AB  - An epidemiological study was set up in the 1980s of UK participants in the UK
      atmospheric nuclear weapons testing programme. A large cohort of test
      participants was established along with a closely matched comparison or control
      group. Three analyses of mortality and cancer incidence have been carried out.
      This review describes the development of the evidence on possible effects on test
      participants with especial emphasis on the most recent analysis. Other sources of
      evidence, particularly from studies of other groups of test participants, are
      also considered. It was concluded that overall levels of mortality and cancer
      incidence in UK nuclear weapons test participants were similar to those in a
      matched control group, and overall mortality was lower than expected from
      national rates. There was no evidence of an increased raised risk of multiple
      myeloma among test participants in recent years, and the suggestion in the first
      analysis of this cohort of a raised myeloma risk relative to controls is likely
      to have been a chance finding. There was some evidence of a raised risk of
      leukaemia other than chronic lymphatic leukaemia among test participants relative
      to controls, particularly in the early years after the tests. Whilst this could
      be a chance finding, the possibility that test participation caused a small
      absolute risk of leukaemia other than chronic lymphatic leukaemia cannot be ruled
      out.

PMID- 15511016
TI  - The bystander effect model of Brenner and Sachs fitted to lung cancer data in 11
      cohorts of underground miners, and equivalence of fit of a linear relative risk
      model with adjustment for attained age and age at exposure.
AB  - Bystander effects following exposure to alpha-particles have been observed in
      many experimental systems, and imply that linearly extrapolating low dose risks
      from high dose data might materially underestimate risk. Brenner and Sachs (2002
      Int. J. Radiat. Biol. 78 593-604; 2003 Health Phys. 85 103-8) have recently
      proposed a model of the bystander effect which they use to explain the inverse
      dose rate effect observed for lung cancer in underground miners exposed to radon
      daughters. In this paper we fit the model of the bystander effect proposed by
      Brenner and Sachs to 11 cohorts of underground miners, taking account of the
      covariance structure of the data and the period of latency between the
      development of the first pre-malignant cell and clinically overt cancer. We also
      fitted a simple linear relative risk model, with adjustment for age at exposure
      and attained age. The methods that we use for fitting both models are different
      from those used by Brenner and Sachs, in particular taking account of the
      covariance structure, which they did not, and omitting certain unjustifiable
      adjustments to the miner data. The fit of the original model of Brenner and Sachs
      (with 0 y period of latency) is generally poor, although it is much improved by
      assuming a 5 or 6 y period of latency from the first appearance of a pre
      malignant cell to cancer. The fit of this latter model is equivalent to that of a
      linear relative risk model with adjustment for age at exposure and attained age.
      In particular, both models are capable of describing the observed inverse dose
      rate effect in this data set.

PMID- 15511017
TI  - Organisation of the disposal of radioactive sources from Scottish hospitals.
AB  - An amnesty for disposal of sealed radioactive sources from Scottish hospitals has
      been funded by the Scottish Executive to address problems arising from
      accumulation of sources. The contract was awarded to a company involved in
      radioactive source recycling. Coordination of uplifts from several hospitals
      allowed considerable financial savings to be made, so source amnesties could
      offer monetary advantages to Health and Education Departments elsewhere in the
      UK, as well as alleviating the problem from security and storage of sources that
      are no longer required. The sources originated in 14 hospitals, but were uplifted
      from five pick-up points. There were a total of 246 sources with 167 of these
      being caesium-137. The total activity was 16.2 TBq with one large 16.1 TBq blood
      irradiator source and the activities of all the other sources adding up to 167
      GBq. This paper describes organisation of the collection. Options for achieving
      compliance with the Radioactive Substances Act 1993 are discussed, although in
      the event, special authorisations were obtained for each hospital. Arrangements
      for transport of the sources and source security were drawn up including
      emergency procedures for dealing with foreseeable incidents. The police provided
      secure overnight storage for the loaded truck and assistance in directing and
      monitoring progress of the load.

PMID- 15511018
TI  - On homogeneity within critical groups.
AB  - Since the 1960s, the methodology recommended by the International Commission on
      Radiological Protection (ICRP) for assessment of individual doses has developed
      significantly, yet the specific recommendations related to the characteristics of
      'critical groups' for the purposes of protection of the public have been
      interpreted but are relatively unchanged. This paper examines developments
      relevant to the criteria for appropriate homogeneity of habits within critical
      groups. It is suggested that, with the need for additivity of effective doses
      summed over different contributing exposure pathways, an important criterion for
      selection of the critical group is homogeneity of summed effective doses rather
      than, necessarily, of the underlying factors such as ages and habits focusing on
      a particular pathway. This implies that there need be less emphasis than before
      on the term 'critical pathway'. However, examples of recent retrospective
      assessments near UK nuclear establishments are given and it is shown that, in
      practice, critical groups selected on the basis of summed effective doses are
      still fairly homogeneous in terms of detailed habits.

PMID- 15511019
TI  - Thermoluminescence dosimetric properties of a new thin beta detector (LiF:Mg, Cu,
      P; GR-200F) in comparison with highly sensitive Al2O3:C beta dosimeters.
AB  - There is an increasing need for efficient beta detectors to fulfil ICRU
      recommendations for new quantities especially in the field of medical physics and
      retrospective dosimetry. The thermoluminescence properties of thin LiF:Mg, Cu, P
      (GR-200F) tapes produced in 1998 by Sange Company, People's Republic of China,
      are investigated and compared with those of highly sensitive thin Al2O3:C beta
      detectors as regards their applicability in the detection of low energy photons
      and beta particles. The radiation dose response, minimum detectable dose,
      reproducibility of measurements and effect of residual signal at low dose are
      assessed for the possible low level beta dosimetry use. The radiation dose
      response and photon and beta detection efficiencies are tested underpractical
      laboratory conditions. The effects of indoor fluorescent light and residual
      signal after the first read-out are investigated with a view to optimising
      handling conditions such as post-irradiation and pre-heating treatments for
      routine dosimetry. The photon energy responses of the detectors are investigated
      using 150 keV filtered x-rays and 60Co gamma-rays.

PMID- 15511020
TI  - Time trends of thyroid cancer incidence in Ukraine after the Chernobyl accident.
AB  - The rate of childhood thyroid cancer incidence observed in northern Ukraine
      during the period 1986-1998 is described as a function of time-since-exposure,
      age-at-exposure, and sex. Conclusions are drawn for the excess absolute risk per
      dose: after a minimal latency period of about three years it shows a linear
      increase with time-since-exposure for at least nine years. It is roughly constant
      in age-at-exposure, up to 15 years. For girls exposed very young it is about a
      factor 2 larger than for boys. For children exposed at age 16-18 this ratio
      increases to about 5. The thyroids of young children are not more sensitive to
      radiation dose than those of older ones in absolute risk in northern Ukraine in
      the currently used data set. As the background is increasing with age, a constant
      absolute risk gives a decreasing relative risk.

PMID- 15511021
TI  - High radon exposure in a Brazilian underground coal mine.
AB  - The main source of radiation exposure in most underground mining operations is
      radon and radon decay products. The situation of radon exposure in underground
      mining in Brazil is still unknown, since there has been no national regulation
      regarding this exposure. A preliminary radiological survey in nonuranium mines in
      Brazil indicated that an underground coal mine in the south of Brazil had high
      radon concentration and needed to be better evaluated. This paper intends to
      present an assessment of radon and radon decay product exposure in the
      underground environment of this coal mining industry and to estimate the annual
      exposure to the workers. As a product of this assessment, it was found that
      average radon concentrations at all sampling campaign and excavation sites were
      above the action level range for workplaces of 500-1500 Bq m(-3) recommended by
      the International Commission on Radiological Protection--ICRP 65. The average
      effective dose estimated for the workers was almost 30 times higher than the
      world average dose for coal miners.

PMID- 15511022
TI  - Time-integrated thyroid dose for accidental releases from Pakistan Research
      Reactor-1.
AB  - The two-hourly time-integrated thyroid dose due to radio-iodines released to the
      atmosphere through the exhaust stack of Pakistan Research Reactor-1 (PARR-1),
      under accident conditions, has been calculated. A computer program, PAKRAD (which
      was developed under an IAEA research grant, PAK/RCA/8990), was used for the dose
      calculations. The sensitivity of the dose results to different exhaust flow rates
      and atmospheric stability classes was studied. The effect of assuming a constant
      activity concentration (as a function of time) within the containment air volume
      and an exponentially decreasing air concentration on the time-integrated dose was
      also studied for various flow rates (1000-50000 m3 h(-1)). The comparison
      indicated that the results were insensitive to the containment air exhaust rates
      up to or below 2000 m3 h(-1), when the prediction with the constant activity
      concentration assumption was compared to an exponentially decreasing activity
      concentration model. The results also indicated that the plume touchdown distance
      increases with increasing atmospheric stability.

PMID- 15511023
TI  - The bell should toll for the linear no-threshold model.
AB  - The linear no-threshold (LNT) model has been a convenient tool in the practice of
      radiation protection but it is not supported by scientific data at doses less
      than about 100 mSv or at chronic dose rates up to at least 200 mSv yr(-1).
      Radiation protection practices based on the LNT model yield no demonstrable
      benefits to health when applied at lower annual doses. The assumption that such
      exposures are harmful may not even be conservative and has helped to foster an
      unwarranted fear of low-level radiation. For its new recommendations, to be
      issued probably in 2005, the ICRP has said that it expects to continue the
      application of the LNT model 'above a few millisieverts per year'. National
      societies for radiation protection may wish to consider the need to lobby the
      ICRP, through the auspices of IRPA, to further relax adherence to the LNT
      assumption-up to 'a few tens of millisieverts per year'.

PMID- 15511024
TI  - Dental x-rays and low birth weight.

PMID- 15511025
TI  - Radioactive waste management.

PMID- 15511026
TI  - Radioactive waste management.

PMID- 15511027
TI  - Risks of non-cancer disease incidence and mortality in the Japanese atomic bomb
      survivors.

PMID- 15511028
TI  - SRP meeting on radiological terrorism: prevention and response.

PMID- 15511029
TI  - Sharps injuries in the operating room--a new focus for OSHA.

PMID- 15511030
TI  - Humanity: idea, image, reality.

PMID- 15511031
TI  - Dignity and psychotherapeutic considerations in end-of-life care.
AB  - The basic tenets of palliative care are frequently subsumed under the goal of
      helping patients to die with dignity. Our research group has studied the issue of
      dignity, with dying patients serving as the primary informants. This paper
      reviews some of our findings, including an overview of the Dignity Model that
      derives from our empirical work. Furthermore, this paper summarizes various
      psychotherapeutic approaches which have been considered for this vulnerable
      patient population. Finally, we provide the rationale based on the Dignity Model
      for a psychotherapeutic intervention we have coined Dignity Therapy. This brief,
      individualized therapeutic approach has been informed by our dignity work, and
      specifically designed for application in patients nearing death.

PMID- 15511033
TI  - Lost in translation: dignity dialogues at the end of life.
AB  - After a diagnosis of life-threatening illness, decisions must be made regarding
      various treatment options including life-sustaining interventions. The
      preservation of dignity is commonly invoked in these discussions with patients,
      their substitute decision makers, and health care providers. Current thoughts on
      dignity explore two main ideas: dignity as intrinsic worth and dignity as worth
      judged according to extrinsic socially based constructs. For the most part, both
      notions of dignity are appealed to in discussions of continuing or
      withholding/withdrawing treatments and in debates on the legalization of assisted
      death. These conceptions of dignity are value-laden and frequently biased, and
      therefore should be used with caution, if at all, in discussions with patients
      and their substitute decision makers. The fundamental issues in discussion with
      all patients diagnosed with a life-threatening illness are ones of respect for
      persons, acceptance, caring, and the value of interpersonal relationships.

PMID- 15511032
TI  - Unilateral withholding and withdrawal of potentially life-sustaining treatment: a
      violation of dignity under the law in Canada.
AB  - In this paper, I review Canadian law in relation to the unilateral withholding or
      withdrawal of potentially life-sustaining treatment, and I look at such questions
      as whether physicians are legally permitted to unilaterally put a do-not
      resuscitate (DNR) order on a patient's chart. I explore who has the legal
      authority in Canada to decide on withholding and withdrawal of potentially life
      sustaining treatment, and I conclude that unilateral withholding and withdrawal
      is a violation of the strong social commitment to dignity as it is understood and
      reflected in the law by the Supreme Court of Canada. I then offer a concrete
      proposal for institutional policy with respect to unilateral withholding and
      withdrawal of treatment in light of the law.

PMID- 15511034
TI  - Is physician-assisted death only for developed countries? Latin America as a case
      study.
AB  - The achievements of modern medicine are manifold and impressive. However, there
      is a broad recognition of the fact that continuing medical treatment is not
      always beneficial to the patient, nor is it always what the patient wants. This
      has led to a debate about the way physicians may or may not be involved in the
      end of life of patients. Could there be a justification for the active ending of
      a patient's life? This debate has a global character. In this article we will
      explore this debate for developing countries; we will focus on physician-assisted
      death (PAD) in Latin American countries. At stake is the moral relevance of
      differences, not the moral justification of PAD per se. We argue that arguments
      for PAD apply equally in affluent and in developing countries. Some of the
      counterarguments, however, would seem to hold more in developing countries than
      in affluent countries. Yet, under certain conditions, a policy tolerating PAD
      would be as acceptable in developing countries as in developed countries.

PMID- 15511035
TI  - Dignity at the end of our days: personal, familial, and cultural location.
AB  - The desire to be treated with dignity, particularly at the end of one's life, is
      a fairly universal preference found in most cultures. Such treatment requires
      positive actions of respect in the behaviour of others toward the dying and the
      dead. It also involves negative actions, particularly refraining from doing
      "dignatory harms" to the dead and the dying. Yet it is not always easy for
      clinicians and researchers who deal with the dying and dead to decide on
      appropriate action or inaction. I suggest that such decision making can be helped
      by locating the dying person along three dimensions: the personal, the familial,
      and the cultural. These elements are interrelated in complex ways that need to be
      unpacked in context. Thus, one person may locate herself within a familial
      context while a sibling may locate himself against that context. While locating
      individuals along the three dimensions suggested does not "solve" ethical
      problems, it should help clinicians in understanding and dealing more
      compassionately with the dead, the dying, their families, and their communities.

PMID- 15511036
TI  - Death, dignity, and moral nonsense.
AB  - Although the concept of human dignity is widely invoked in discussions regarding
      end-of-life decision making, the content of the notion is ambiguous. Such
      ambiguity has led some to conclude that human dignity is a redundant or even
      useless concept that we would be better off without. This paper argues, to the
      contrary, that the concept of human dignity is indispensable to moral discourse.
      Far from dispensing with human dignity, we must work to clarify the concept. The
      paper outlines two distinct but related conceptions of dignity that are often
      conflated in contemporary moral discourse. These conceptions are labelled "basic
      dignity" and "personal dignity", respectively. It is argued that basic dignity
      functions as a universal meaning constraint on moral discourse in general. Hence,
      to dispense with the notion could reduce us to speaking moral nonsense.
      Throughout the discussion, some implications for our understanding of end-of-life
      decision making are explored.

PMID- 15511037
TI  - Pity, modernity and the spectacle of suffering.
AB  - The concept of dignity is often invoked in relation to ideas about a "good" death
      and, indeed, a "good" life. In this article, I discuss the question of dignity in
      relation to the rights of the individual in the modern world. This world is one
      where the relationship of individuals to society is contested in the context of
      medicine, with all its technologies of treatment and uncertainties of prognosis.
      For patients who criticize or oppose medicine in order to recover their dignity,
      it is necessary to articulate or to portray their suffering. In this way, they
      are able to show not only that they live in spite of illness, but that they also
      live by virtue of it. From this perspective, dignity is shown to be part of a
      collective response to a medicalized world in which ideas about illness and
      health are also being transformed.

PMID- 15511038
TI  - Harms to dignity, bioethics, and the scope of biolaw.
AB  - Dignity is an expansive ideal, figuring in international covenants, codes of
      research involving human participants, and debates about decision making at the
      end of life. One result of this expansiveness is that human dignity can be
      appropriated by proponents on both sides of many issues, thereby appearing more
      as a rhetorical flourish than as a serious element in argumentation. However, an
      appreciation of narrative inquiry shows that opposing representations of dignity
      constitute alternative assessments of responsible action, both of which can be
      morally reasonable. One implication is that normative disagreements, as between
      deathbed decisions about palliative care or euthanasia, can be expected to occur,
      so that the ideal of dignity should be legally expressed in a practice of
      supportive laissez-faire in preference to any undue regulation of dying.

PMID- 15511039
TI  - Living and dying with dignity: reflections on lived experience.
AB  - Considerations of human dignity figure prominently in discussions of health care,
      and are central in the debate with regard to end-of-life care and the issue of
      physician-assisted suicide. In this paper I reflect on my experience as a person
      living with multiple sclerosis in order to explore ways in which prevailing
      cultural values contribute to the loss of dignity that accompanies incurable
      illness and disability. I suggest that authentic Christian community may offer an
      alternative culture with a radically different value system, one that enhances
      human dignity.

PMID- 15511040
TI  - Death with dignity: contested boundaries.

PMID- 15511041
TI  - Dignity, dialogue, and care.

PMID- 15511042
TI  - Reflections on the human dignity symposium: is dignity a useless concept?

PMID- 15511043
TI  - Outcomes of congenital heart disease: a review.
AB  - One million Americans are affected by congenital heart disease (CHD) (American
      Heart Association [AHA], 2003). As survival has improved, evidence has
      accumulated that CHD touches many aspects of the lives of those affected.
      Children and adults report difficulties with physical growth and/or stature.
      Gross motor abnormalities are common in both groups, and significantly reduced
      exercise tolerance is reported in adults with CHD, including those with minor
      defects. Behavioral and psychiatric abnormalities are reported in adolescents and
      young adults, including a significant incidence of depression and anxiety
      disorders. The data are conflicting regarding quality of life (QOL) in children
      and adults with CHD. More research is needed examining outcomes, particularly
      outcomes of those diagnosed, managed, and repaired using modern technology.

PMID- 15511044
TI  - Breastfeeding success among infants with congenital heart disease.
AB  - It is a widespread misconception that infants with congenital heart disease (CHD)
      are not able to breastfeed. The purpose of this study was to describe
      breastfeeding duration and outcomes among a high-risk group of infants with CHD.
      Mothers of 68 infants at least 6 months of age, who had experienced cardiac
      surgery during the neonatal period, were surveyed regarding breastfeeding and
      milk expression habits. Results for this sample of infants were compared to a
      benchmark study conducted in 1993 at the same institution that described
      breastfeeding outcomes for 45 infants with CHD. Improved outcomes for the 1998
      2000 sample are attributed to an active lactation consultation program instituted
      in 1998. These findings suggest that given support and education necessary to
      initiate and maintain lactation, mothers can successfully breastfeed their
      infants with CHD for durations recommended by the Healthy People 2010 initiative.

PMID- 15511045
TI  - Management of chylothorax in children.
AB  - Chylothorax is a collection of a white milky drainage from the lymphatic system
      within the thoracic cavity that can impair respiratory status as it accumulates.
      Management of this uncommon complication of thoracic surgery can include: total
      parenteral nutrition (TPN), low-fat enteral nutrition, thoracentesis to remove
      the chylous fluid, and surgical ligation of the thoracic duct, as well as
      octreatide infusion to control splanchnic blood flow. Nursing management of these
      patients can be complex and challenging.

PMID- 15511046
TI  - Rural low-income mothers' interactions with their young children.
AB  - Quality mother-child interaction is imperative for normal child growth and
      development. Early intervention programs may support mother-child interaction,
      particularly at-risk mother-child dyads. The purpose of this study was to
      describe mother-child dyadic interaction as they entered and exited a rural Early
      Head Start (EHS) program and compare their interaction with a normed national
      sample. Thirty mothers and their children participated in the study and agreed to
      allow trained data collectors to observe an in-home teaching situation using the
      Nursing Child Assessment Satellite Training (NCAST) Teaching Scale. At exit from
      the program, although no significant differences in mother-child interactions
      were found, more than half of the mothers maintained or improved their ability to
      read cues and respond to their child. However, over 40% of the mothers remained
      at risk for poor interaction. Differences in program outcomes may be a result of
      family participation and involvement levels. Poor maternal health may also
      adversely affect mother-child interaction. Program implications include resource
      allocation for those mothers with the greatest "worry" scores. Nurses and other
      professionals working with mothers and children need to be vigilant in their
      ongoing assessment of the mother's health and possible influence on the quality
      of the mother-child interaction.

PMID- 15511047
TI  - Children with special health care needs: national survey of prevalence and health
      care needs.

PMID- 15511048
TI  - Child care health consultants' roles and responsibilities: focus group findings.
AB  - PURPOSE: To describe the roles and responsibilities of newly trained health
      professionals, primarily nurses called Child Care Health Consultants. METHOD:
      Health professionals hired by county agencies to become Child Care Health
      Consultants enrolled in the California Training Institute (CTI) for Child Care
      Health Consultants, a 9-day educational training program divided into three
      modules. They participated in one focus group during each module. Research staff
      led the focus groups and the participants were asked, "What are your roles and
      responsibilities?" Qualitative analyses were conducted and common themes were
      identified. FINDINGS: The nine focus groups included 44 participants, 95% were
      nurses with an average of 20 years of work experience. The roles and
      responsibilities of the Child Care Health Consultants were described by five
      themes: network, education, sustainability, on-site service, and administration.
      CONCLUSION: These findings contribute to the new field of child care health
      consultation by defining the common roles and responsibilities of Consultants.

PMID- 15511049
TI  - Fever management in children who are febrile is questionable.

PMID- 15511050
TI  - Fever management in children who are febrile is questionable.

PMID- 15511051
TI  - Integrating levels of evidence into clinical decision making.

PMID- 15511052
TI  - Pediatric management problems. Intussusception.

PMID- 15511053
TI  - Pediatric medical errors part 1: the case. A pediatric drug overdose case.

PMID- 15511054
TI  - Pediatric medical errors part 2: case commentary. A source of tremendous loss.
AB  - The Dowdell (2004) case report chills the reader. We must learn through its
      publication methods of prevention of medication error. The attached guidelines
      provided by the ISMP can lead us in a more cautious direction. Knowledge of the
      float regulations would have required that the involved hospital had ensured that
      a float nurse to pediatrics understood that medication dosages were weight
      dependent and that calculations were required prior to drug administration.
      Adequate staffing might have prevented the need for a float nurse and allowed for
      more attention to double checking calculations and drug administration.
      Dissemination of the guidelines from the AAP or those recommended by the SPN
      might have prevented this error. The age-old story of impoverished physician
      nurse interaction has outlived its place in history. Nurse-physician collegiality
      and investment in the team approach will save children's lives.

PMID- 15511055
TI  - Pediatric medical errors part 3: safety strategies. Medication use system to
      analyze errors.

PMID- 15511056
TI  - Go-kart trauma--the heart of the matter.

PMID- 15511057
TI  - Evidence-based hospital design improves health care outcomes for patients,
      families, and staff.

PMID- 15511058
TI  - Pediatric Nursing's 2004 Humanitarian Award. Recipient: Cathy Robinson-Pickett.

PMID- 15511059
TI  - Early marriage and HIV risks in sub-Saharan Africa.
AB  - This article examines the effects of girls' early marriage on their risk of
      acquiring HIV/AIDS. By comparing several underlying HIV risk factors, it explores
      the counterintuitive finding that married adolescent girls in urban centers in
      Kenya and Zambia have higher rates of HIV infection than do sexually active
      unmarried girls. In both countries, we find that early marriage increases coital
      frequency, decreases condom use, and virtually eliminates girls' ability to
      abstain from sex. Moreover, husbands of married girls are about three times more
      likely to be HIV-positive than are boyfriends of single girls. Although married
      girls are less likely than single girls to have multiple partners, this
      protective behavior may be outweighed by their greater exposure via unprotected
      sex with partners who have higher rates of infection. These results challenge
      commonly held assumptions about sex within marriage.

PMID- 15511060
TI  - Bridging the gap between evidence-based innovation and national health-sector
      reform in Ghana.
AB  - Although experimental trials often identify optimal strategies for improving
      community health, transferring operational innovation from well-funded research
      programs to resource-constrained settings often languishes. Because research
      initiatives are based in institutions equipped with unique resources and staff
      capabilities, results are often dismissed by decisionmakers as irrelevant to
      large-scale operations and national health policy. This article describes an
      initiative undertaken in Nkwanta District, Ghana, focusing on this problem. The
      Nkwanta District initiative is a critical link between the experimental study
      conducted in Navrongo, Ghana, and a national effort to scale up the innovations
      developed in that study. A 2002 Nkwanta district-level survey provides the basis
      for assessing the likelihood that the Navrongo model is replicable elsewhere in
      Ghana. The effect of community-based health planning and services exposure on
      family planning and safe-motherhood indicators supports the hypothesis that
      Navrongo effects are transferable to impoverished rural settings elsewhere,
      confirming the need for strategies to bridge the gap between Navrongo evidence
      based innovation and national health-sector reform.

PMID- 15511061
TI  - Abortion-related maternal mortality in the Russian Federation.
AB  - This study examines characteristics and determinants of maternal mortality
      associated with induced and spontaneous abortion in the Russian Federation. In
      addition to national statistical data, the study uses the original medical files
      of 113 women, representing 74 percent of all women known to have died after
      undergoing an abortion in 1999. The number of abortions and abortion-related
      maternal deaths fell fairly steadily during the 1991-2000 decade to levels of 56
      percent and 52 percent of the 1991 base, respectively. Regional and urban-rural
      variation is limited. Nine percent of abortion-related maternal mortality is due
      to spontaneous abortion; 24 percent is related to induced abortions performed
      inside and 67 percent to those performed outside a medical institution. In the
      latter group, older women, usually with a history of several pregnancies, are
      overrepresented. The high rate of abortion-related maternal mortality is due
      largely to the number of abortions performed at 13-21 weeks' and 22-27 weeks'
      gestation both inside and outside medical institutions. Improving access to safe
      second-trimester abortion, preventing delays during the abortion procedure, and
      adequate treatment of complications are key strategies for reducing abortion
      related maternal mortality.

PMID- 15511062
TI  - Long-term effects of reproductive history on all-cause mortality among adults in
      rural Bangladesh.
AB  - A woman's risk of dying is altered during pregnancy and immediately postpartum.
      Moreover, physiological and social changes associated with pregnancy may have
      long-term effects on mortality. Comparing these long-term associations among
      women and their husbands may provide insights into the nature of such a
      relationship. In this cohort study, we examine the association between
      reproductive history and all-cause mortality among ever-married women and men
      after age 45 in Matlab, Bangladesh, using data collected between 1982 and 1998
      for a unique demographic surveillance system. No association was found between
      parity and mortality among women, but a small decrease in men's mortality was
      found to be associated with their wives' parity. Survival for both sexes was
      greatly enhanced by an increasing number of surviving children, regardless of
      parity or other social factors. A "healthy pregnant woman effect" coupled with
      the social and economic advantages of having surviving children may explain the
      observed effects.

PMID- 15511063
TI  - Changes in American opinion about family planning.
AB  - A 1998 public opinion survey conducted in the United States indicated high levels
      of support for many family planning policies, including US health insurance
      coverage of family planning services and US sponsorship of family planning
      programs in developing countries. To gauge changes in opinion on these issues
      since then, some of the 1998 questions were asked in an omnibus 2003 survey. The
      results indicate continuing high support for requiring US health insurers to
      cover family planning services (87 percent in 1998 and 84 percent in 2003), but
      some loss of support (from 80 to 69 percent) for US sponsorship of family
      planning programs in developing countries. Opinion remains divided on the policy
      of prohibiting nongovernmental organizations from receiving federal funding for
      performing or actively promoting abortion services. The authors explore several
      possible explanations for these findings, including the role changing
      presidential policy may have had in shaping opinion regarding family planning aid
      for developing countries.

PMID- 15511064
TI  - Nicaragua 2001: results from the Demographic and Health Survey.

PMID- 15511065
TI  - Zambia 2001-2002: results from the Demographic and Health Survey.

PMID- 15511066
TI  - [Enhancement of immunogenicity of hCGbeta protein vaccine and the hCG
      neutralization capacity of anti-serum by using the molecular adjuvant C3d3].
AB  - To enhance the immunogenicity of hCGbeta protein vaccine and the hCG
      neutralization capacity of anti-serum by using the molecular adjuvant C3d3, the
      secreted 6his-hCGbeta-C3d3 fusion protein and 6his-hCGbeta were expressed in CHO
      cells and purified with Ni(2+)-chelating chromatography and Sephadex G-150
      column. Then we investigated the potential of three copies of C3d as the
      molecular adjuvant of hCGbeta protein antigen. The antibody response to hCGbeta
      C3d3 conjugates was compared with those resulting from immunization with hCGbeta
      alone and hCGbeta plus CFA/IFA in BALB/c mice. Our results showed that the
      antibody titer of hCGbeta-C3d3 was 1995-fold higher than that of hCGbeta alone
      and the anti-serum was capable effectively neutralizing the bioactivity of hCG.
      The immunity-enhancing action of C3d3 was 10-fold (primer) and 32-fold (booster)
      greater than CFA/IFA. These results indicated that C3d3 conjugates might be a
      better way to overcome the poor immunogenicity of hCGbeta contraceptive vaccine.

PMID- 15511067
TI  - [Study on the formaldehyde-induced DNA damage with comet assay].
AB  - Formaldehyde is known as a genotoxic substance. Numerous studies have shown that
      formaldehyde could induce DNA-DNA and DNA-protein crosslinks. However, scholars
      have disagreed with each other on the formaldehyde-induced DNA strand breaks. We
      chose buccal cells as materials to evaluate the genotoxicity of formaldehyde with
      comet assay--especially for DNA strand breaks. The results showed that
      formaldehyde of low concentration induced DNA strand breaks, while formaldehyde
      of high concentration induced DNA-DNA and DNA-protein crosslinks. According to
      our experimental results, we proposed the concept of the "peak point of break" at
      which formaldehyde induced DNA strand breaks most.

PMID- 15511068
TI  - [Cloning of potato invertase inhibitor St-inh cDNA and its expression in E. coli
      and functional analysis].
AB  - A full length cDNA clone encoding invertase inhibitor was isolated by RT-PCR
      combined with 5' RACE from potato (S. tuberosum) tubers of cv. JH and designated
      as St-inh. The encoding region of St-inh is of 663bp encoding a protein of 221
      amino acids. The DNA fragment including St-inh cDNA was cloned into the vector
      pET28a (+) and expressed successfully in E. coli. Co-incubation of the proteins
      produced by St-inh in E. coli and the invertase extracts from potato tubers of
      cv. E1, JH and tomato fruits showed that the invertase activities of potato
      tubers and tomato fruits decreased by 34.3%, 21% and 33.8% respectively. These
      results indicated that products of St-INH protein had a function of invertase
      inhibitors. The analysises of the nucleotide and amino acid sequences using BLAST
      and T-COFFEE demonstrated that St-inh cDNA was of over 95% homologous to Kunitz
      type C and there was a typical domain of Kunitz-type protein [L, I, V, M]-X-D-X
      [E, D, N, T, Y-[D, G]-[R, K, H, D, E, N, Q]-X-[L, I, V, M]-X(5)-Y-X-[L, I, V, M.
      Therefore, it was conjectured that St-inh could be a member of Kunitz-type gene
      family.

PMID- 15511069
TI  - [Studies on the ploymorphic of sperm of F2 hybrids of red crucian carp x common
      carp].
AB  - AThe ultrastructures of the sperm of F2 hybrids of red crucian carp x common carp
      were studied by using scanning and transmission electron microscope. The sperm of
      the F2 hybrids consisted of head, mid-piece and tail. There was no acrosome at
      the anterior end of the nuclears, whereas there was a vesicle. The results
      revealed that there existed obviously ploymorphic in the sperm of F2 hybrids. In
      the water-like semen from males of F2 hybrids, different sizes of the head of the
      sperm including haploid, diploid, tetraploid, and aneuploid sperm were observed.
      The head diameter of the smallest sperm was only 1.32 microm, but that of the
      biggest one was about 18.39 microm, and most of them varied from 1.85 to 2.15
      microm. The haploid sperm was normal, while the a-neuploid, diploid, tetraploid
      and multiploid sperm were abnormal. Among the abnormal sperm, there was a super
      sperm with about 20 tails, whose head volume was much bigger than that of any
      other sperm. From the results of the transmission electron microscope, 3 sperm
      with two nucleus and 1 sperm with two tails were found. This study provided an
      useful evidence for the mechanism that the formation of tetraploid in F3 hybrids
      was due to the fertilization of the diploid eggs and diploid sperm produced by F2
      hybrids.

PMID- 15511070
TI  - [Expression pattern of profilin homologue in embryogenesis of amphioxus].
AB  - The expression pattern of profilin homologue in embryogenesis of amphioxus was
      characterized by whole-mount in situ hybridization combined serial histological
      sections and Northern blot. The results revealed that the dynamic expression
      pattern of the profilin homologue just accorded with muscle differentiating in
      this animal. It was most possibly involved in the development of muscle in
      amphioxus. The result of Southern blot supported that there was only one copy of
      profilin homologue in the genome of Qingdao amphioxus. It may be good for
      explaining the molecular mechanism of muscle differentiation in amphioxus.

PMID- 15511071
TI  - [Study on the expression of nm23-M1/NDPK a during the blastocyst adhesiveness in
      the mouse endometrium].
AB  - The nm23 gene was originally identified as a metastasis suppressor gene by
      differential hybridization of non-metastatic and metastatic clones of murine K
      1735 melanoma cell lines. Subsequently, other highly homologous genes were
      characterized and shown to code for nucleoside diphosphate kinase (NDPK)
      isotypes. These enzymes have been evidenced in a wide variety of organisms. In
      human, up to eight distinct but highly related genes have been discovered. The
      nm23-H1 and nm23-H2 gene products share 88% identity and are about 95% and 98%
      identical to the murine nm23-M1 and nm23-M2 proteins respectively. A number of
      data indicate that nm23 family, initially documented as metastasis suppressors in
      some cancer types, are involved in the control of normal development,
      differentiation and apoptosis. The trophoblast cells of blastocyst and of the
      normal first-trimester placenta share some phenotypic similarities with malignant
      cells, such as rapid proliferation and ability to invade neighbouring tissues,
      including basement membrane, during the process of implantation and placental
      development, but do not have the ability for unlimited growth or metastasis, as
      few trophoblast cells can be identified in the deciduas, and trophoblasts rarely
      penetrate the maternal blood vessels. Although some data indicate that nm23
      family play an important role in regulation of reproductive processes, little is
      know about its actual mechanism. In our studies, we performed RT-PCR, Western
      blot and immunohistochemical analyses of nm23-M1/NDPK A expression during the
      blastocyst adhesiveness in the mouse endometrium. The nm23-M1 mRNA expression was
      shown progressive increase in D5 mice endometrium by RT-PCR, which was consistent
      with the result obtained by Western blot and immunohistochemistry. It is
      suggested that nm23-M1/NDPK A was involved in the process of blastocyst
      implantation.

PMID- 15511072
TI  - [The cytochemical observation of anthers of Chinese cabbage's male-sterile].
AB  - A Chinese cabbage (Brassica campestris L. ssp. chinensis Makino) produces 1/4
      male sterile and 3/4 fertility in offspring. The sterile plant can be identified
      from the color of corolla that is some white when it grows out. The fertile and
      sterile anthers were researched using cytological and cytochemical methods. Thick
      sections of both anthers of different developmental stages were stained with
      Toluidine blue for general cytological observation and stained with the periodic
      acid-Schiff's (PAS) technique to detect polysaccharides (red), with Sudan black B
      (SBB) to detect lipids (black). Before meiosis of microspore mother cells,
      connective tissue of both fertile and sterile anthers stored a lot of starch
      grains. Neither starches nor lipid drops were in tapetal and microspore mother
      cells. The only difference of both anthers was that the tapetal cells of sterile
      anthers contained more vacuoles than those of fertile anthers. After meiosis of
      microspore mother cells, the starch grains in connective tissue of fertile
      anthers disappeared, the tapetal cells synthesized abundant lipid drops, and the
      microspores also began to accumulate lipid drops. In sterile anthers, the starch
      grains in connective tissue also disappeared, but only a few lipid drops appeared
      in tapetal cells. The tapetal cells, however, became red, suggesting the cell
      contained some polysaccharide material. Pollen abortion in sterile anthers
      occurred in this stage. The aborting microspores accumulated very less lipid
      drops in its cytoplasm than those in fertile the starch This result suggested
      that in the cabbage, the starch grains in connective tissue were transformed into
      polysaccharide and transported to tapetal cells, then these cells transformed
      polysaccharide into lipid material that was absorbed by developing microspore. In
      sterile anthers, however, polysaccharide in the tapetal cells could not be
      transformed to lipid. The functional default of tapetal cells during lipid
      metabolism led to microspore abortion. This is new sample in which the functional
      default of tapetal cells will make pollen abort, and will enhance research field
      in male sterile in higher plants.

PMID- 15511073
TI  - [Embryonic lung cell allografts under the renal capsule--a new model for the
      study of lung development].
AB  - Lung is a critical respiratory organ of living body. The regulation of lung
      morphogenesis, especially the epithelial development in the late fetal stages, is
      not completely understood due to lack of efficiency strategies. In this study we
      showed that the growth of dissociated embryonic lung cells implanted underneath
      the kidney capsules of syngeneic hosts followed closely lung development in
      utero. The epithelium developed extensively and appeared to go through
      pseudoglandular stage, canallicular stage, and saccular stage at a pace similar
      to normal lung development. At the same time, the capillary-like vascular
      developed also. The greatest advantage of this model was that the dissociated
      single cells uptake antisence oligo at a high level, and introduced phenotype
      after grafting. Embryonic lung cell renal capsule graft is thus an excellent
      model for the study of lung morphogenesis.

PMID- 15511074
TI  - [Activity assay, antiserum preparation and cellular localization of ustiloxins].
AB  - False smut is an increasingly important rice disease in recent years, caused by a
      pathogen, Ustilaginoidea virens Cooke, Takahashi. The pathogen fungus grew well
      in PD medium, and could produce toxins, ustiloxins, which strongly inhibited the
      growth of radicle and embryo of plants. The rough ustiloxins were extracted with
      100% methanol from the culture filtrate in the study. The antiserum against
      Ustiloxin A, the main component of the toxins, was raised by immunizing New
      Zealand rabbit. Elisa assay showed that the titers of the two antiserums obtained
      were 1: 20 000 and 1: 6 000, respectively. The specificity of the antiserums was
      also confirmed by Immuno-gold labeling.

PMID- 15511075
TI  - [Ethanol affects the function of gamma-aminobutyric acid transporter I in mice
      brain].
AB  - It has been suggested that GABAergic system was involved in ethanol tolerance and
      addiction. Our previous work indicated both acute and chronic ethanol treatment
      enhanced the activity of GABA transporters in mouse brain. However, the
      expression level of GAT1 in CNS does not change, neither does the affinity of
      GABA transporters. In the present study, we demonstrated that GAT1 distribution
      on presynaptic membrane was altered after acute and chronic ethanol
      administration. Furthermore, the phosphorylation levels of GAT1 on three sites
      including Ser, Tyr and Thr were decreased. These data suggested that ethanol
      enhanced the function of GATs by means of inducing GAT1 redistribution in the
      cell and dephosphorylation may play a role in this process.

PMID- 15511076
TI  - [Relationship of Sa, No and H2O2 signals in the reponses of Arabidopsis to toxin
      of Verticillium dahliae].
AB  - The accumulation of hydrogen peroxide (H2O2) in Arabidopsis was induced by toxin
      of Verticillium dahliae (VD-toxin), exogenous salicylic acid (SA) and nitric
      oxide donor (SNP). The effect of SNP was the most intense. H2O2 level was not
      increased in Arabidopsis treated with nitric oxide synthase inhibitor (NNA). It
      was identified with the results of DAB staining of H2O2 accumulates in the leaves
      of Arabidopsis. H2O2 was cytochemically detected in the cells of epidermal hair
      and the cell wall of vascular parenchyma cell. The results suggest that H2O2 acts
      as a second messenger to involve the defenses in Arabidopsis induced by SA and NO
      signal transduction. The relationship of NO and H2O2 signals was likely closer.

PMID- 15511077
TI  - [Histological observation on programmed cell death in wheat-leaf rust fungus
      intreaction].
AB  - The biochemical character of PCD in different interaction between wheat and
      Puccinia recondita f. sp tritici was observed using DNA agarose gel
      electrophoresis and end labeling in situ (Terminal Deoxynucleotidyl Transferase
      mediated dUTP Nick End TUNEL). The DNA ladder, which is the typical character of
      programmed cell death(PCD), was observed in incompatible combination (cv.lorvin10
      x race 162) and the positive reaction in wheat leaves of incompatible combination
      since 12h after inoculation also appeared. The results, coupled with the previous
      study, indicated that HR was a typical form of PCD in incompatible combination
      between wheat and wheat leaf fungus.

PMID- 15511078
TI  - [Optimization of reaction conditions for RAPD analysis of freshwater planarians
      in China].
AB  - Using the Genomic DNA purification kit, the total DNA of the freshwater planarian
      was extracted and developed one single band through 0.8% agarose gel
      electrophoresis with OD260/OD280 between 1.5 and 2.2, which could satisfy the
      requirements of RAPD and PCR on DNA. With the extracted DNA template, we tested
      experimental conditions that might affect RAPD results including annealing
      temperature, concentrations of template DNA, primer, Mg2+ and dNTPs. Through
      comparision we found that it was necessary and important to optimize the
      experimental conditions for producing stable and repeatable RAPD results. The
      optimized reaction conditions of RAPD for freshwater planarian in 25 microl
      reaction volume were as follows: 20 ng template DNA, 37 degrees C annealing
      temperature, 0.2 micromol/L primer, 2.0 mmol/L Mg2+ and 200 micromol/L dNTPs.

PMID- 15511079
TI  - From the neuromuscular junction to cellular architecture and beyond--commentary
      on 30 years of imaging by John E. Heuser.

PMID- 15511080
TI  - My colloboration with John Heuser.

PMID- 15511081
TI  - Ultrastructure in cell biology: do we still need it?
AB  - John Heuser is being honored in this special issue for his enormous contributions
      to cell biology using morphological approaches. Foremost in this context is his
      ability to use light and electron microscopy to visualize structures and
      processes such that the information has both scientific and artistic value. The
      beauty of his images helps to focus the observer more intensely on the scientific
      messages, which have been numerous and important. His recent studies of living
      cells using state-of-the-art light and video microscopy fits into a general
      pattern of a huge explosion in the application of these methods worldwide that is
      revolutionizing cell biology. However, whereas John Heuser continues to use light
      microscopy (LM) for a low-resolution global and dynamical overview he then moves
      on to the electron microscopy (EM) level to see the details; in this he is-
      unfortunately--in a minority; and EM is an approach that a majority of today's
      cell biologists never use. The continued drop in EM usage has already been
      articulated in recent reviews. Here, I suggest that an additional problem for EM
      in cell biology, in its continued crises, is the declining number of scientists
      who can confidently interpret the--admittedly--complex information in most
      electron micrographs of cells. A major re-education is needed, or cell biology as
      a discipline will have a real problem in the 21st century.

PMID- 15511082
TI  - John Heuser's contributions to the visualization of the actin cytoskeleton by
      electron microscopy.

PMID- 15511083
TI  - The GGA proteins: key players in protein sorting at the trans-Golgi network.
AB  - The GGA (Golgi-localized, gamma-ear containing, ADP-ribosylation factor binding)
      family of multidomain coat proteins was first described in the year 2000. They
      are now known to occupy a central position in the trafficking of the mannose 6
      phosphate receptors and other cargo molecules from the trans-Golgi network to the
      endosome/lysosome system. This review covers the recent structural and cell
      biological studies that have provided mechanistic insights into the function of
      the GGAs in mannose 6-phosphate receptor trafficking.

PMID- 15511084
TI  - Dicumarol, an inhibitor of ADP-ribosylation of CtBP3/BARS, fragments golgi non
      compact tubular zones and inhibits intra-golgi transport.
AB  - Dicumarol (3,3'-methylenebis[4-hydroxycoumarin]) is an inhibitor of brefeldin-A
      dependent ADP-ribosylation that antagonises brefeldin-A-dependent Golgi
      tubulation and redistribution to the endoplasmic reticulum. We have investigated
      whether dicumarol can directly affect the morphology of the Golgi apparatus. Here
      we show that dicumarol induces the breakdown of the tubular reticular networks
      that interconnect adjacent Golgi stacks and that contain either soluble or
      membrane-associated cargo proteins. This results in the formation of 65-120-nm
      vesicles that are sometimes invaginated. In contrast, smaller vesicles (45-65 nm
      in diameter, a size consistent with that of coat-protein-I-dependent vesicles)
      that excluded cargo proteins from their lumen are not affected by dicumarol. All
      other endomembranes are largely unaffected by dicumarol, including Golgi stacks,
      the ER, multivesicular bodies and the trans-Golgi network. In permeabilized
      cells, dicumarol activity depends on the function of CtBP3/BARS protein and pre
      ADP-ribosylation of cytosol inhibits the breakdown of Golgi tubules by dicumarol.
      In functional experiments, dicumarol markedly slows down intra-Golgi traffic of
      VSV-G transport from the endoplasmic reticulum to the medial Golgi, and inhibits
      the diffusional mobility of both galactosyl transferase and VSV-G tagged with
      green fluorescent protein. However, it does not affect: transport from the trans
      Golgi network to the cell surface; Golgi-to-endoplasmic reticulum traffic of
      ERGIC58; coat-protein-I-dependent Golgi vesiculation by AlF4 or ADP-ribosylation
      factor; or ADP-ribosylation factor and beta-coat protein binding to Golgi
      membranes. Thus the ADP-ribosylation inhibitor dicumarol induces the selective
      breakdown of the tubular components of the Golgi complex and inhibition of intra
      Golgi transport. This suggests that lateral diffusion between adjacent stacks has
      a role in protein transport through the Golgi complex.

PMID- 15511085
TI  - Effects of dynamin inactivation on pathways of anthrax toxin uptake.
AB  - Internalization and traffic to acidic endosomes of anthrax lethal factor (LF) and
      protective antigen (PA), bound to the anthrax toxin receptor (ATR), is required
      for LF translocation into the cytosol, where it can elicit its toxic effects.
      Dynamin is required for clathrin-mediated endocytosis, and long-term disruption
      of dynamin function blocks internalization of PA. We have used LFn-DTA, a
      surrogate of LF consisting of the N-terminal domain of LF fused to the catalytic
      subunit of diphtheria toxin, to differentiate the effects of acute and long-term
      block of dynamin function on LFn-DTA toxicity. Both forms of interference reduce
      LFn-DTA toxicity only partially, consistent with alternative routes for LFn-DTA
      endocytosis. In contrast, a long-term block of dynamin activity results in a
      further interference with LFn-DTA toxicity that is consistent with an altered
      endosomal environment, probably an increase in endosomal pH.

PMID- 15511086
TI  - Distribution of alkaline phosphatase in vegetative dictyostelium cells in
      relation to the contractile vacuole complex.
AB  - The structure of the contractile vacuole complex of Dictyostelium discoideum has
      long been a subject of controversy. A model that originated from the work of John
      Heuser and colleagues described this osmoregulatory organelle as an
      interconnected array of tubules and cisternae the membranes of which are densely
      populated with vacuolar proton pumps. A conflicting model described this same
      organelle as bipartite, consisting of a pump-rich spongiome and a pump-free
      bladder, the latter membranes being identified by their alkaline phosphatase
      activity. In the present study we have employed an antiserum specific for
      Dictyostelium alkaline phosphatase to examine the distribution of this enzyme in
      vegetative cells. The antiserum labels puncta, probably vesicles, that lie at or
      near the plasma membrane and are sometimes, but only rarely, enriched near
      contractile vacuole membranes. We conclude that alkaline phosphatase is not a
      suitable marker for contractile vacuole membranes. We discuss these results in
      relation to the two models of contractile vacuole structure and suggest that all
      data are consistent with the first model.

PMID- 15511087
TI  - GFP-golvesin constructs to study Golgi tubulation and post-Golgi vesicle dynamics
      in phagocytosis.
AB  - Dictyostelium cells are professional phagocytes that are optimally suited for the
      imaging of phagosome processing from particle uptake to exocytosis. In order to
      design fluorescent probes for monitoring membrane trafficking in the endocytic
      pathway, we have dissected a membrane protein, golvesin, and have linked
      fragments of its sequence to GFP. Endogenous golvesin is partitioned between the
      ER, the Golgi apparatus, endosomes, and the contractile vacuole complex. We have
      localized signals that are required for exit from the Golgi to post-Golgi
      compartments to the C-terminal region of the golvesin sequence. One GFP-tagged
      fragment turned out to be a highly specific Golgi marker and was used to
      demonstrate the interaction of Golgi tubules with phagosomes. Signals essential
      for the retrieval of golvesin at the end of phagosome processing were localized
      to the N-terminal region. A truncated golvesin construct escaping retrieval was
      employed in recording the delivery of a phagosomal protein to the plasma
      membrane. Applying this construct to a phagosome filled with multiple particles,
      we observed that the phagosome is segmented during exocytosis, meaning that
      sequential release of particles alternates with membrane fusion.

PMID- 15511088
TI  - Role of rab5 in EGF receptor-mediated signal transduction.
AB  - Activated epidermal growth factor receptor (EGFR) recruits intracellular proteins
      that mediate receptor trafficking and signaling. Rab5 and Rin1, a multifunctional
      protein with a Rab5 guanine nucleotide exchange factor domain, have been shown to
      regulate EGFR endocytosis (Barbieri et al., 2000; Tall et al., 2001). In this
      study, we demonstrate that overexpression of both dominant negative Rab5
      (Rab5:S34N) and full-length Rin1 selectively block EGF activation of the Raf
      Erk1/2 kinase pathway and EGF-stimulated incorporation of [3H]thymidine into DNA
      without affecting the activity of JN and p38 kinase pathways. Expression of
      Rab5:S34N and Rin1 also block EGF induction of cyclin D1 transcription. In
      contrast, expression of Rin1:delta, a natural splice variant of Rin1 lacking 47
      amino acids in the Vps9p domain or Rab5, increase both activation of Raf-Erk1/2-
      and cyclin D1 transcription in response to EGF. These results indicate that Rab5
      and the Raf/Erk signal transduction pathway play essential and selective roles in
      EGF-induced cell proliferation, and highlight a new function for Rab5 in EGF
      signaling.

PMID- 15511089
TI  - A world model, a model world.

PMID- 15511090
TI  - "Beware of all enterprises that require new clothes" (Henry David Thoreau, 1817
      1862).

PMID- 15511091
TI  - Finding fugacity feasible, fruitful, and fun.
AB  - A review is presented concerning the evolution of the fugacity concept as applied
      to environmental science. The series of serendipitous events that ultimately
      resulted in publication of the paper "Finding Fugacity Feasible" in 1979 is
      described. The use of fugacity as a surrogate for concentration is shown to
      facilitate the compilation and solution of mass-balance equations. It has proved
      to be valuable in a number of contexts, notably the description of chemical fate
      in unit worlds at various levels of complexity. More complex systems can be
      simulated as sets of connected unit worlds. The fugacity approach enables the
      multimedia character of organic chemicals to be deduced, thus contributing to the
      evaluation of chemical properties that impact persistence and long-range
      transport. It has proved to be especially insightful for describing
      bioconcentration, bioaccumulation, and pharmacokinetic phenomena. Applications to
      the sensing and monitoring of chemical presence in the environment are described.
      Suggestions are made for subject areas in which the fugacity concept may prove to
      be particularly valuable in the future. Finally, the many colleagues who have
      contributed to the use of fugacity when quantifying chemical behavior in the
      environment are acknowledged.

PMID- 15511092
TI  - Finding and estimating chemical property data for environmental assessment.
AB  - The ability to predict the behavior of a chemical substance in a biological or
      environmental system largely depends on knowledge of the physicochemical
      properties and reactivity of that substance. We focus here on properties, with
      the objective of providing practical guidance for finding measured values and
      using estimation methods when necessary. Because currently available computer
      software often makes it more convenient to estimate than to retrieve measured
      values, we try to discourage irrational exuberance for these tools by including
      comprehensive lists of Internet and hard-copy data resources. Guidance for
      assessors is presented in the form of a process to obtain data that includes
      establishment of chemical identity, identification of data sources, assessment of
      accuracy and reliability, substructure searching for analogs when experimental
      data are unavailable, and estimation from chemical structure. Regarding property
      estimation, we cover estimation from close structural analogs in addition to
      broadly applicable methods requiring only the chemical structure. For the latter,
      we list and briefly discuss the most widely used methods. Concluding thoughts are
      offered concerning appropriate directions for future work on estimation methods,
      again with an emphasis on practical applications.

PMID- 15511093
TI  - Universal predictive models on octanol-air partition coefficients at different
      temperatures for persistent organic pollutants.
AB  - Owing to the importance of octanol-air partition coefficients (KOA) in describing
      the partition of organic pollutants from air to environmental organic phases, the
      paucity of KOA data at different environmental temperatures, and the difficulty
      or high expenditures involved in experimental determination, the development of
      predictive models for KOA is necessary. Approaches such as this are greatly
      needed to evaluate the environmental fate of the ever-increasing list of
      production chemicals. Partial least squares (PLS) regression with 18 molecular
      structural descriptors was used to develop predictive models based on directly
      measured KOA values of selected chlorobenzenes, polychlorinated biphenyls (PCBs),
      polychlorinated naphthalenes, polychlorinated dibenzo-p-dioxins/dibenzofurans,
      polybrominated diphenyl ethers, polycyclic aromatic hydrocarbons, and
      organochlorine pesticides (OPs). An optimization procedure resulted in two
      temperature-dependent universal predictive models that explained at least 91 % of
      the variance of log KOA. Model 1 was the more general of the two models that
      could be used for all the persistent organic pollutant (POP) classes
      investigated. Although model 1 performed poorly for select OPs, this was
      attributed to wide variability in structural types within this subset of POPs and
      their diversity compared to the other POP classes that were investigated. The
      exclusion of the structurally complex OP subset resulted in a more precise model,
      model 5. Intermolecular dispersive interactions (induced dipole-induced dipole
      forces) between octanol and solute molecules play a decisive role in governing
      KOA and its temperature dependence. Further investigations are needed to better
      characterize the steric structures of the POPs under study, especially of OPs.

PMID- 15511094
TI  - Adsorption of polycyclic aromatic hydrocarbons at the air-water interface and its
      role in atmospheric deposition by fog droplets.
AB  - This review addresses the significance of air-water interfacial adsorption in the
      fate and transport of polycyclic aromatic hydrocarbons (PAHs) in dispersed
      systems, such as fog droplets in the atmosphere and air bubbles in wastewater
      systems. The equilibrium (partition constants) and transport (mass accommodation
      coefficients) parameters in dispersed systems are discussed. Specific cases where
      the air-water interfacial adsorption makes a significant impact, such as uptake
      of naphthalene by fog droplets in a falling droplet reactor and of pyrene removal
      on air bubbles in a solvent sublation reactor, are discussed as illustrations.
      The consequence of the air-water interface in atmospheric wet deposition of PAHs
      by fog droplets is analyzed mathematically.

PMID- 15511095
TI  - Intestinal absorption and biomagnification of organic contaminants in fish,
      wildlife, and humans.
AB  - Methods for the regulatory assessment of the bioaccumulation potential of organic
      chemicals are founded on empirical measurements and mechanistic models of dietary
      absorption and biomagnification. This study includes a review of the current
      state of knowledge regarding mechanisms and models of intestinal absorption and
      biomagnification of organic chemicals in organisms of aquatic and terrestrial
      food chains and also includes a discussion of the implications of these models
      for assessing the bioaccumulation potential of organic chemicals. Four
      mechanistic models, including biomass conversion, digestion or gastrointestinal
      magnification, micelle-mediated diffusion, and fat-flush diffusion, are
      evaluated. The models contain many similarities and represent an evolution in
      understanding of chemical bioaccumulation processes. An important difference
      between the biomagnification models is whether intestinal absorption of an
      ingested contaminant occurs solely via passive molecular diffusion through serial
      resistances or via facilitated diffusion that incorporates an additional
      advective transport mechanism in parallel (i.e., molecular ferrying within
      gastrointestinal micelles). This difference has an effect on the selection of
      physicochemical properties that best anticipate the bioaccumulative potential of
      commercial chemicals in aquatic and terrestrial food chains. Current regulatory
      initiatives utilizing Kow threshold criteria to assess chemical bioaccumulation
      potential are shown to be unable to identify certain bioaccumulative substances
      in air-breathing animals. We urge further research on dietary absorption and
      biomagnification of organic chemicals to develop better models for assessing the
      bioaccumulative nature of organic chemicals.

PMID- 15511096
TI  - Soil-air relationships for toxaphene in the southern United States.
AB  - Volatilization of toxaphene residues from agricultural soil was investigated at
      farms in the southern United States by collecting air samples 40 cm above the
      soil. The concentration of total toxaphene ranged over several orders of
      magnitude, from <3 to 6,500 ng g(-1) dry weight in soil, and <0.3 to 42 ng m(-3)
      in air. A log-log plot of total toxaphene concentrations in soil and overlying
      air showed a significant (p < 0.001) positive relationship, with r2 = 0.73. The
      soil/air fugacity ratio (FR) for 26 events ranged from 0.4 to 238, exceeded FR =
      1.0 (soil/air equilibrium) in 24 events, and exceeded FR = 10 in 17 events. This
      indicates that toxaphene in air sampled at 40 cm generally was not at equilibrium
      but undersaturated with respect to the soil. Compared to a technical toxaphene
      standard, chromatographic profiles of toxaphene residues in soil and air showed
      alterations due to preferential degradation and volatilization of the components.
      Peaks matching the retention times of labile octachlorobornanes B8-531 and B8-806
      + B8-809 were depleted in both soil and air relative to the more recalcitrant B8
      1413 + B8-1945 and B8-2229. For each event, log-log plots were made of the
      dimensionless soil/air concentration quotient (Q) versus liquid-phase vapor
      pressure (PL, Pa) for 10 toxaphene components (peaks containing coeluting
      congeners) that spanned the volatility range of hepta- to nonachlorobornanes.
      Statistically significant linear relationships were obtained with r2 values for
      most events ranging from 0.54 to 0.96. Slopes for all but one event ranged from 
      1.01 to -1.53 and averaged -1.28 +/- 0.20. When regressions were carried out for
      only components one to nine, which cover the vapor pressure range of most
      components reported in ambient air, the average slope was reduced to -1.02 +/-
      0.15. Previous models of toxaphene emission, transport, and deposition have
      considered only total toxaphene. These results provide a basis for modeling
      soil/air exchange on the basis of single congeners or groups of congeners having
      similar volatilities.

PMID- 15511097
TI  - A food web bioaccumulation model for organic chemicals in aquatic ecosystems.
AB  - The present study examines a new bioaccumulation model for hydrophobic organic
      chemicals in aquatic food webs. The purpose of the model is to provide site
      specific estimates of chemical concentrations and associated bioconcentration
      factors, bioaccumulation factors, and biota-sediment accumulation factors in
      organisms of aquatic food webs using a limited number of chemical, organism, and
      site-specific data inputs. The model is a modification of a previous model and
      incorporates new insights regarding the mechanism of bioaccumulation derived from
      laboratory experiments and field studies as well as improvements in model
      parameterization. The new elements of the model include: A model for the
      partitioning of chemicals into organisms; kinetic models for predicting chemical
      concentrations in algae, phytoplankton, and zooplankton; new allometric
      relationships for predicting gill ventilation rates in a wide range of aquatic
      species; and a mechanistic model for predicting gastrointestinal magnification of
      organic chemicals in a range of species. Model performance is evaluated using
      empirical data from three different freshwater ecosystems involving 1,019
      observations for 35 species and 64 chemicals. The effects of each modification on
      the model's performance are illustrated. The new model is able to provide better
      estimates of bioaccumulation factors in comparison to the previous food web
      bioaccumulation model while the model input requirements remain largely
      unchanged.

PMID- 15511098
TI  - A food chain model to predict the levels of lipophilic organic contaminants in
      humans.
AB  - A fugacity-based, nonsteady state, mechanistic model called ACC-HUMAN was
      developed to describe bioaccumulation of lipophilic organic pollutants from air,
      water, and soil to humans. The physical environment was linked via a marine and
      an agricultural food chain model to a human bioaccumulation model. Contaminant
      uptake via the primary dietary sources of persistent lipophilic contaminants in
      industrialized countries was addressed, namely fish, dairy products, and beef. In
      addition, uptake from air and water was considered, allowing the model also to
      treat less lipophilic compounds. To evaluate the model, the food chain
      characteristics were parameterized for southern Sweden and historical scenarios
      of polychlorinated biphenyl (PCB) concentrations in air, water, and soil in this
      region were constructed from published data. The resulting model predictions of
      PCB concentrations in fish, milk, beef, and human tissue agreed well with
      measured concentrations from Swedish monitoring programs. This suggests that ACC
      HUMAN is a useful tool for predicting human exposure to bioaccumulative organic
      compounds. It can be linked easily to existing multimedia fate and transport
      models.

PMID- 15511099
TI  - Biological and chemical factors of importance in the bioaccumulation and trophic
      transfer of persistent organochlorine contaminants in Arctic marine food webs.
AB  - Recent studies of arctic marine food webs have provided detailed insights
      regarding the biological and chemical factors that influence the bioaccumulation
      and trophic transfer of persistent organochlorine (OC) contaminants in aquatic
      systems. The present paper summarizes the recent literature with an emphasis on
      identifying important ecological factors for explaining variability of OC
      concentrations among organisms. The Arctic ecosystem has a number of unique
      attributes, including long food chains, reduced diversity of species, similar
      food webs across the entire region, and limited influence from pollution point
      sources. Lipid content, body size, age, gender, reproduction, habitat use,
      migration, biotransformation, seasonal changes in habitat conditions, feeding
      ecology, and trophic position have all been demonstrated to influence OC
      concentrations and bioaccumulation in arctic marine biota. The relative
      importance of each factor varies among OCs and organisms. Diet or trophic level
      is the dominant factor influencing OC concentrations and dynamics in seabirds and
      marine mammals, although biotransformation can significantly influence
      nonrecalcitrant OCs, such as hexachlorocyclohexane isomers. Dietary accumulation
      of OCs is also an important route of exposure for arctic fish and zooplankton,
      and biomagnification of OCs may also occur among these organisms. To date, only
      limited attempts have been made to model trophic transfer of OCs in the arctic
      marine food web. Although models developed to assess OC dynamics in aquatic food
      webs have included some biological variables (e.g., lipid content, feeding rate,
      diet composition, and growth rate), selection of processes included in these
      models as well as their mathematical solutions and parameterization all introduce
      simplification. This reduces biological validity of the models and may be
      particularly problematic in a highly seasonal environment, such as the Arctic
      Ocean.

PMID- 15511100
TI  - Modeling the fate of polychlorinated biphenyls in the inner Oslofjord, Norway.
AB  - A dynamic, segmented, multimedia fate and transport model has been developed,
      evaluated, and applied to gain insight regarding the behavior of seven
      polychlorinated biphenyl (PCB) congeners in the Inner Oslofjord (Norway). A
      comparison with a dated sediment core reveals that the model is not capable of
      reproducing some key features of the observed, historical, long-term trend in
      sediments, although better agreement is observed for six of seven PCB congeners
      over the last two decades. The model also underestimates the concentrations of
      PCBs in surface sediments in areas adjacent to the city of Oslo (Norway). In
      general, deviations between modeled and observed concentrations indicate that the
      historical emissions and discharges of PCBs are not sufficiently characterized
      and described. Net fluxes predicted by the model suggest that several congeners
      may have experienced a reversal of air-water and seawater-sediment exchange
      during the last decade or even earlier. The present study further suggests that
      the benefit of the proposed removal of the most contaminated sediments of the
      Inner Oslofjord needs to be assessed, with consideration of the relative
      contribution of current atmospheric inputs as well as the leaching of PCBs from
      less contaminated sediments.

PMID- 15511101
TI  - The long-term fate of polychlorinated biphenyls in San Francisco Bay (USA).
AB  - A simple one-box mass budget model is presented as a first step toward a
      quantitative understanding of the long-term fate of polychlorinated biphenyls
      (PCBs) in San Francisco Bay (USA). Sensitivity analysis indicated that the most
      influential input parameters were degradation half-life in sediment, Kow,
      outflow, average PCB concentration in sediment, and depth of the active sediment
      layer. Moderately influential parameters included organic carbon content of
      suspended solids, sediment burial mass transfer coefficient, and Henry's law
      constant. If external loading could be eliminated entirely, the mass of PCBs in
      the bay is predicted to drop to half of the present value in 20 years. The model
      predicts that sustained loading of 10 kg year(-1) would prevent the total PCB
      mass in the bay from ever dropping below 10% of the present mass. With a
      sustained loading of 20 kg year(-1), the model predicts that the total PCB mass
      would never fall below about 25% of the present mass. The half-lives in the bay
      for the individual PCB congeners evaluated in this report ranged from four years
      for PCB 18 to 30 years for PCB 194.

PMID- 15511102
TI  - Dynamic coupled metal transport-speciation model: application to assess a zinc
      contaminated lake.
AB  - A coupled metal transport and speciation/complexation model (TRANSPEC) has been
      developed to estimate the speciation and fate of multiple interconverting species
      in surface aquatic systems. Dynamic-TRANSPEC loosely, sequentially couples the
      speciation/complexation and fate modules that, for the unsteady state
      formulation, run alternatively at every time step. The speciation module first
      estimates species abundance using, in this version, MINEQL+ considering time
      dependent changes in water and pore-water chemistry. The fate module is based on
      the quantitative water air sediment interaction (QWASI) model and
      fugacity/aquivalence formulation, with the option of using a pseudo-steady state
      solution to account for past discharges. Similarly to the QWASI model for organic
      contaminants, TRANSPEC assumes the instantaneous equilibrium distribution of
      metal species among dissolved, colloidal, and particulate phases based on ambient
      chemistry parameters that can be collected through conventional field methods.
      The model is illustrated with its application to Ross Lake (Manitoba, Canada)
      that has elevated Zn concentrations due to discharges over 70 years from a mining
      operation. Using measurements from field studies, the model reproduces year-round
      variations in Zn water concentrations. A 10-year projection for current
      conditions suggests decreasing Zn remobilization and export from the lake.
      Decreasing Zn loadings increases sediment-to-water transport but decreases water
      concentrations, and vice versa. Species distribution is affected by pH such that
      a decrease in pH increases metal export from the lake and vice versa.

PMID- 15511103
TI  - Empirical and modeling evidence of regional atmospheric transport of current-use
      pesticides.
AB  - Water samples from 30 lakes in Canada and the northeastern United States were
      analyzed for the occurrence of 27 current-use pesticides (CUPs). Eleven CUPs were
      frequently detected in lakes receiving agricultural inputs as well as in remote
      lakes hundreds of kilometers from known application areas. These included the
      triazine herbicide atrazine and its desethylated degradation product; the
      herbicides alachlor, metolachlor, and dacthal; the organophosphate insecticides
      chlorpyrifos, diazinon, and disulfoton; the organochlorine insecticides alpha
      endosulfan and lindane; and the fungicides chlorothalonil and flutriafol. For six
      of the pesticides, empirical half-distances on the order of 560 to 1,820 km were
      estimated from the water-concentration gradient with latitude. For most of the
      pesticides, a suite of assessment models failed to predict such atmospheric long
      range transport behavior, unless the effect of periods of lower hydroxyl radical
      concentrations and dry weather were taken into account. Observations and model
      results suggest that under the conditions prevailing in south-central Canada
      (relatively high latitude, low precipitation rates), many CUPs will be able to
      undergo regional-scale atmospheric transport and reach lakes outside areas of
      agricultural application. When assessing the potential of fairly reactive and
      water-soluble substances to undergo long-range transport, it is imperative to
      account for periods of no precipitation, to assure that degradation rate
      constants are correct, and to apply oxidant concentrations that are valid for the
      region and time period of interest.

PMID- 15511104
TI  - Investigating the mechanics of multimedia box models: how to explain differences
      between models in terms of mass fluxes?
AB  - The simple mathematical structure of multimedia fate models makes it possible to
      change the process descriptions and geometry of such models relatively easily.
      With different versions of a model, the effect of a process or compartment that
      is included in one version of the model but excluded in another version can be
      investigated. Here, a new method for performing such a model comparison in a
      quantitative way is presented. Based on the mass balances for the two model
      versions, it can be shown that, for a compartment contained in both model
      versions, the difference between a chemical's concentrations in this compartment
      is related directly to the difference in those mass fluxes that have different
      rate constants in the two models. Moreover, it is possible to identify the
      contributions to the concentration difference that stem from individual mass
      fluxes so that the concentration difference can be tracked back to specific
      differences in the process descriptions of the two models. This flux analysis
      method is illustrated with two versions of a unit-world model, one with and one
      without a vegetation compartment. With DDT and six polychlorinated biphenyl (PCB)
      congeners as example chemicals, the differences of the chemicals' concentrations
      in air and soil caused by the vegetation compartment are explained by using the
      flux analysis method. The future potential of the method for comparing not only
      versions of the same model but also models of different structure is discussed.

PMID- 15511105
TI  - Oil spill impact modeling: development and validation.
AB  - A coupled oil fate and effects model has been developed for the estimation of
      impacts to habitats, wildlife, and aquatic organisms resulting from acute
      exposure to spilled oil. The physical fates model estimates the distribution of
      oil (as mass and concentrations) on the water surface, on shorelines, in the
      water column, and in the sediments, accounting for spreading, evaporation,
      transport, dispersion, emulsification, entrainment, dissolution, volatilization,
      partitioning, sedimentation, and degradation. The biological effects model
      estimates exposure of biota of various behavior types to floating oil and
      subsurface contamination, resulting percent mortality, and sublethal effects on
      production (somatic growth). Impacts are summarized as areas or volumes affected,
      percent of populations lost, and production foregone because of a spill's
      effects. This paper summarizes existing information and data used to develop the
      model, model algorithms and assumptions, validation studies, and research needs.
      Simulation of the Exxon Valdez oil spill is presented as a case study and
      validation of the model.

PMID- 15511106
TI  - Obtaining quantitative vapor emissions estimates of polychlorinated biphenyls and
      other semivolatile organic compounds from contaminated sites.
AB  - Soils contaminated with polychlorinated biphenyls (PCBs) and other semivolatile
      organic compounds (SVOCs) represent a potentially major, ongoing source of these
      compounds to the environment, especially during warmer temperatures. A great deal
      of work has been devoted to understanding the mechanisms that govern the
      vaporization of SVOCs from soil, but to date, few quantitative estimates have
      been published regarding emissions from contaminated sites. The present paper
      describes methods for obtaining quantitative estimates of SVOCs from soils based
      on flux chamber measurements, modeling, and ambient air measurements. On wet
      (i.e., H2O) soils, SVOCs at very low chemical loading levels on the adsorption
      sites (the so-called critical chemical concentration, critical loading, or
      saturation concentration) will behave, for volatilization purposes, as the pure
      liquid substance would. For one soil, the PCB critical concentration was
      determined to be 775 ppm (95% confidence interval, 5.40E+02). Flux chamber
      measured emissions from two contaminated sites were used and compared to model
      estimated values. The results agree reasonably well and indicate that the
      modeling approach used provided a conservative upper bound on the emissions.
      These approaches can be used to develop emissions estimates for SVOC-contaminated
      sites and inputs to air dispersion models.

PMID- 15511107
TI  - Multimedia persistence as an indicator of potential for population-level intake
      of environmental contaminants.
AB  - Although intuitively it is apparent that population-level exposure to
      contaminants dispersed in the environment must be related to the persistence of
      the contaminant, there has been little effort to quantify this link formally. In
      this paper we investigate the relationship between overall persistence and/or
      overall residence time in a multimedia exposure environment and the population
      level intake of contaminants as expressed by intake fraction (iF), the cumulative
      fraction of chemical emitted to the environment that is taken up by members of
      the population. We demonstrate that for any given contaminant and emission
      scenario the definition of iF implies that it is directly proportional to the
      overall multimedia persistence (Pov), or the overall multimedia residence time
      (Tov). The proportionality constant has dimensions of time and represents the
      characteristic time for population intake (CTI) of the chemical from the
      environment. We then apply the CalTOX fate and exposure model to explore how Tov
      and CTI combine to determine the magnitude of iF We find that CTI has a narrow
      range of possible values relative to Tov across multiple chemicals and emissions
      scenarios. We use data from the Canadian Environmental Protection Act Priority
      Substance List (PSL1) Assessments and multimedia Pov to show that exposure
      assessments based on empirical observation are consistent with interpretations
      from the model. Results indicate that Pov derived from screening-level
      assessments of persistence, bioaccumulation potential, and toxicity (PBT) is a
      useful indicator of the potential for population-level exposure.

PMID- 15511108
TI  - Putting science into persistence, bioaccumulation, and toxicity evaluations.
AB  - In recent decades, advances have been made in the processes used to identify
      substances as persistent, bioaccumulative, and toxic (PBT). Key processes have
      been identified, and scientifically sound assessment methods have been developed.
      Regulatory agencies around the world have sought practical methods for
      implementing policies to protect both environment and human health. In the
      present paper, we review the various contributions that Mackay (in collaboration
      with his students and colleagues) has made to the development of scientifically
      sound methods for the identification of PBT substances and persistent organic
      pollutants. These contributions include efforts to clearly define the terminology
      and to develop scientifically defensible assessment models and evaluation
      frameworks.

PMID- 15511109
TI  - Integrated fate modeling for exposure assessment of produced water on the Sable
      Island Bank (Scotian shelf, Canada).
AB  - Produced water is the largest waste discharge from the production phase of oil
      and gas wells. Produced water is a mixture of reservoir formation water and
      production chemicals from the separation process. This creates a chemical mixture
      that has several components of toxic concern, ranging from heavy metals to
      soluble hydrocarbons. Analysis of potential environmental effects from produced
      water in the Sable Island Bank region (NS, Canada) was conducted using an
      integrated modeling approach according to the ecological risk assessment
      framework. A hydrodynamic dispersion model was used to describe the wastewater
      plume. A second fugacity-based model was used to describe the likely plume
      partitioning in the local environmental media of water, suspended sediment,
      biota, and sediment. Results from the integrated modeling showed that the soluble
      benzene and naphthalene components reach chronic no-effect concentration levels
      at a distance of 1.0 m from the discharge point. The partition modeling indicated
      that low persistence was expected because of advection forces caused by tidal
      currents for the Sable Island Bank system. The exposure assessment for the two
      soluble hydrocarbon components suggests that the risks of adverse environmental
      effects from produced water on Sable Island Bank are low.

PMID- 15511110
TI  - Probabilistic uncertainty analysis of the European Union system for the
      evaluation of substances multimedia regional distribution model.
AB  - The European Union System for the Evaluation of Substances (EUSES) is a
      computerized model system to facilitate and harmonize health and environmental
      risk assessment of previously notified and new substances. For calculation of
      regional background exposure, a multimedia distribution model is used. In the
      present study, the uncertainty of this regional model is analyzed. Environmental
      parameters were collected for North Rhine Westphalia (Germany), which resembles
      the standard region of EUSES. Probability distribution functions of various types
      (uniform, triangular, normal, log normal) depending on data availability were
      derived for environmental input parameters, including geometric parameters.
      Generic log-normal distribution functions with fixed standard deviations were
      chosen for solubility in air, water, and n-octanol as well as for degradation
      half-lives. Monte Carlo simulations were carried out for 10 reference substances
      having different properties. Contribution of environmental parameter uncertainty
      to total output uncertainties is higher than that of substance parameters. Range
      of output uncertainty, defined as the ratio of the logarithms of the 90th and
      10th percentiles of the cumulative probability distribution function, shows an
      increase from air and water to soil. The highest-occurring range is 1.4 orders of
      magnitude, which means that total uncertainty of the regional model is relatively
      low and, usually, is lower than the range of measured values. The median of
      output probability distributions lies above the point estimate. Influence of
      input parameters was estimated as their rank correlation coefficients to output
      uncertainty. Substance and environmental parameters contribute differently to
      output variance depending on individual substance properties and environmental
      compartment. Hence, the present study underlines the need to perform uncertainty
      analyses instead of either using a set of simple rules or just looking at certain
      parameters.

PMID- 15511111
TI  - Application of the narcosis target lipid model to algal toxicity and deriving
      predicted-no-effect concentrations.
AB  - The narcosis target lipid model (TLM) was developed to predict the toxicity of
      chemicals to aquatic organisms that act via narcosis. It is based on the
      hypothesis that target lipid is the site of toxic action within the organism,
      that octanol is the appropriate surrogate, and that target lipid has the same
      physical-chemical properties in all organisms. Here the TLM is extended to
      available freshwater green algal toxicity data to support a narcosis toxic mode
      of-action (TMoA) effect assessment. For each species, significant linear
      relationships were observed between log(median effective concentration [EC50])
      and log(Kow) of the test chemicals. The slope of the log-log relationship
      statistically was similar to the universal narcosis slope of -0.945 that was
      derived from an earlier analysis of the TLM to nonalgal species. Critical target
      lipid body burdens (CTLBB), C(L)* were estimated for each algal species from the
      intercepts of the regressions and found to be within the range (43-398 micromol/g
      octanol) reported previously, indicating that algae exhibit a similar sensitivity
      distribution relative to other aquatic species. The TLM is used to derive the
      predicted-no-effect concentrations (PNECs) using the hazardous concentration to
      5% species (HC5) statistical extrapolation procedure. This calculation requires
      an analysis of the variability of the universal slope, the C(L)*, and the acute
      to-chronic ratio. The PNECs derived using this procedure were consistent with
      chronic-no-effect concentrations reported for narcotic chemicals. This is in
      contrast to PNECs derived from limited chemical-specific toxicity data and
      default application factors. It is concluded that coupling the TLM to the HC5
      extrapolation procedure allows optimal use of available toxicity data for
      deriving environmental quality criteria with a narcotic TMoA.

PMID- 15511112
TI  - Environmental quality criteria for organic chemicals predicted from internal
      effect concentrations and a food web model.
AB  - Environmental quality criteria (EQC) for hydrophobic organic chemicals were
      calculated with a model for bioaccumulation in food webs. The model was
      calibrated and verified using polychlorinated biphenyl concentrations in food
      webs of shallow lakes. The EQCs in water and sediment were derived based on
      internal effect concentrations (IECs) for several modes of toxic action. By
      reverse calculation with the food web model for each organism in the web, a
      different water or sediment concentration is calculated corresponding to the IEC
      in each organism. A statistical procedure with an acute-to-chronic value is used
      to derive chronic EQCs based on bioaccumulation. The model-based chronic EQCs
      were compared with previously established EQCs. The EQCs calculated with the food
      web model generally are within an order of magnitude of the previously derived
      EQCs based on toxicity data on individual chemicals. Some previously derived EQCs
      are much lower than model predictions and usually based on small samples of
      toxicity data such as no-observed-effect concentrations (NOECs) with large
      assessment factors. When faced with data gaps, it is proposed to use model-based
      chronic EQCs for (polar) narcotic chemicals. Other modes of action require a
      different model concept to account for receptor-based toxicity.

PMID- 15511113
TI  - Psychiatric symptoms, social disability, low wellbeing and need for treatment:
      data from a population-based study.
AB  - BACKGROUND: Identifying need for treatment due to mental problems is necessary
      for rational health care planning. The aim of this study was to study reports of
      psychiatric symptoms, social disability and low wellbeing as indicators of
      meetable need of care. METHODS: An extensive questionnaire was sent out to a
      representative adult population in Stockholm, Sweden. Psychiatric symptom scales,
      social disabilities due to psychological distress and wellbeing were included. Of
      the 10,442 persons that answered 1093 were interviewed by psychiatrists. Meetable
      need of care was assessed and psychiatric diagnoses were made according to DSM
      IV. RESULTS: Reports of psychiatric symptoms, social disabilities and low
      wellbeing were all associated with being female, younger, single, manual work and
      unemployed. Somatic disorders, a lower degree of social network and more negative
      life events were also associated. Of the interviewees persons with low wellbeing
      had the highest risk for being regarded as having meetable need of care.
      Additionally they were more likely to fulfil the criteria for a psychiatric
      disorder according to DSM-IV. CONCLUSION: Persons with low wellbeing had a higher
      risk of having meetable need of care than persons with psychiatric symptoms
      and/or social disabilities had.

PMID- 15511114
TI  - Systemic barriers to quitting smoking among institutionalised public mental
      health service populations: a comparison of two Australian sites.
AB  - BACKGROUND: This article reports the findings from a comparative study
      investigating smoking behaviours among institutionalised psychiatric populations
      from a sociological perspective. METHOD: The study involved participant
      observation of two separate Australian sites between 1999 and 2002, the second
      site serving to generalise the findings from the first site. DISCUSSION AND
      CONCLUSIONS: Systemic barriers to quitting were identified, emanating from the
      mental health system in general. Cigarettes were identified as the currency by
      which economic, social and political exchange took place between participants who
      described an enculturation process that involved complex processes of
      reinforcement to smoke. Once entered into, escape from the smoking culture of the
      settings appeared to be extremely difficult for clients and staff.

PMID- 15511115
TI  - The burden of social phobia in a Brazilian community and its relationship with
      socioeconomic circumstances, health status and use of health services: the Bambui
      study.
AB  - AIMS: Social phobia in the environment of poverty and major social inequalities,
      as observed in most developing countries, has received little attention. This
      population-based study was carried out in a poor community in Brazil (15,000
      inhabitants), aiming at determining the prevalence of social phobia and its
      associated factors. METHOD: The Composite International Diagnostic Interview was
      applied in a random sample of 1037 residents aged > or = 18 years. RESULTS: The 1
      month, 1-year and lifetime prevalence of social phobia were 7.9, 9.1 and 11.8%,
      respectively. One-month social phobia was independently associated with age (45
      64 years), marital status (divorced/separated), worse socioeconomic indicators
      (family income and education), number of months worked, worse health status and
      use of health services and medications. CONCLUSION: There was an important burden
      of social phobia in the study community, due to its high prevalence (similar or
      superior to those observed in most developed countries), and due to its
      association with worse health status and use of health services and medications.
      The strong association between social phobia and socioeconomic circumstance, even
      in a small and poor community, is certainly a reflex of the major social
      inequalities in Brazil.

PMID- 15511116
TI  - Culture-sensitive counselling, psychotherapy and support groups in the Orthodox
      Jewish community: how they work and how they are experienced.
AB  - BACKGROUND: There is political and scientific goodwill towards the provision of
      culture-sensitive support, but as yet little knowledge about how such support
      works and what are its strengths and difficulties in practice. AIMS: To study
      groups offering culture-sensitive psychological and other support to the strictly
      orthodox Jewish community in London. METHODS: Semi-structured interviews with
      service providers, potential and actual users from the community, and
      professionals serving the community. Interviews asked about the aims, functioning
      and achievements of 10 support groups. RESULTS: Thematic analysis identified
      seven important themes: admiration for the work of the groups; appreciation of
      the benefits of culture-sensitive services; concerns over confidentiality and
      stigma; concerns over finance and fund-raising; concerns about professionalism;
      the importance of liaison with rabbinic authorities; need for better
      dissemination of information. CONCLUSIONS: The strengths and difficulties of
      providing culture-sensitive services in one community were identified. Areas for
      attention include vigilance regarding confidentiality, improvements in
      disseminating information, improvements in the reliability of funding and
      attention to systematic needs assessment, and to the examination of efficacy of
      these forms of service provision.

PMID- 15511117
TI  - Social welfare policy: social rehabilitation of psychiatric patients in urban
      China.
AB  - BACKGROUND: The background of this paper is an empirical research on social
      rehabilitation of psychiatric patients in a large urban city in China during the
      post-Mao period, the Beijing Psychiatric Rehabilitation Research. Another aspect
      of this background is an exchange with Chen Sheying, a colleague interested in
      social services for the elderly in China. The underlying assumption of this paper
      is the multiple similarities between those two areas. OBJECTIVES: The first
      objective of this paper is to present a contextual analysis of the development of
      psychiatric rehabilitation in urban China and a second objective is to stress the
      similarities between psychiatric rehabilitation and social services to the
      elderly. MATERIAL: The material presented, while referring mainly to the general
      context of psychiatry and rehabilitation around that period, includes some data
      from the Beijing research. There are five analytical dimensions: (1)
      epistemological choices and research paradigms; (2) rehabilitation as an idea;
      (3) rehabilitation as a social, political and cultural matter; (4) factors of
      change in the recent history of China; and, finally, (5) mental illness as a
      personal experience. DISCUSSION: This presentation leads to a discussion about
      the multiple similarities between the social welfare of two vulnerable categories
      of people (i.e. psychiatric patients and the elderly). It also offers, in the
      specific field of mental illness, a general interpretation of the rapid social
      changes in urban China. CONCLUSION: The conclusion is that psychiatric and ageing
      services are both a product of interaction among various cultural and social
      political-economic factors. Any social welfare intervention or policy should be
      based on a thorough understanding of the five dimensions referred to earlier,
      including the traditional Chinese familism and structural dimensions of the post
      Mao 'economic state' orientation.

PMID- 15511118
TI  - Quality of life of schizophrenic psychiatric outpatients as a criterion for
      treatment planning in psychiatric institutions.
AB  - BACKGROUND: Subjective quality of life (QoL) is an indispensable part of the
      current concept of health. Therefore it should serve as a criterion for treatment
      planning in social psychiatric institutions. AIM: We looked at the QoL of our
      outpatients diagnosed with schizophrenia in order to identify possible areas of
      life that might need further attention in treatment planning. METHODS: We used
      the short German version of the Lancashire Quality of Life Profile (BLEP-KF) to
      evaluate the QoL of 164 schizophrenic outpatients. All patients were diagnosed
      with the International Diagnostic Checklists (IDCL) for ICD-10. Demographic and
      treatment data are analysed cross-sectionally in relation to their QoL. RESULTS:
      The majority of patients was moderately happy with their general QoL. They were
      least satisfied in the domains of job and financial situation, mental health and
      sexuality. Psychopathology and especially the quality of individual care had a
      significant influence on the evaluation of QoL. CONCLUSION: This result supports
      an argument in favour of more individual patient-centred forms of case management
      to reduce the burden of severe psychopathological symptoms experienced in
      everyday activities by patients suffering from schizophrenia.

PMID- 15511119
TI  - Re-thinking acute psychiatric inpatient care.
AB  - BACKGROUND: Reports of low staff morale and high levels of patient complaints
      suggest that acute psychiatric wards are not achieving their full therapeutic
      potential. AIMS: This paper reviews some of the 'therapeutic milieu' literature
      to identify ways of construing ward functioning so as to maximise therapeutic and
      minimise destructive processes within inpatient units. METHOD: Relevant papers
      are reviewed, providing an understanding that permits the inpatient clinician to
      consider and apply the pertinent concepts. RESULTS: Five key therapeutic
      functions of the ward environment are identified containment, support, structure,
      involvement and validation. Four destructive processes are described, relating
      to: the isolated patient; group phenomena; the contribution of staff; and
      structural manifestations in the ward. CONCLUSIONS: The inpatient ward can be
      construed as a 'whole', embodying a range of therapeutic functions, which may
      need rapid deployment and dismantling, as dictated by changes in ward conditions.
      The 'ward-as-a-whole' construct complements individualised models of patient care
      and the practical implications of such thinking could engender a greater sense of
      agency and job satisfaction in staff.

PMID- 15511120
TI  - Culture and intelligence.
AB  - Intelligence cannot be fully or even meaningfully understood outside its cultural
      context. Work that seeks to study intelligence acontextually risks the imposition
      of an investigator's view of the world on the rest of the world. Moreover, work
      on intelligence within a single culture mayfail to do justice to the range of
      skills and knowledge that may constitute intelligence broadly defined and risks
      drawing false and hasty generalizations. This article considers the relevance of
      culture to intelligence, as well as its investigation, assessment, and
      development. Studies that show the importance of understanding intelligence in
      its cultural context are described; the author concludes that intelligence must
      be understood in such context.

PMID- 15511122
TI  - Gold Medal Award for Life Achievement in the Application of Psychology.

PMID- 15511121
TI  - Does psychology make a significant difference in our lives?
AB  - The intellectual tension between the virtues of basic versus applied research
      that characterized an earlier era of psychology is being replaced by an
      appreciation of creative applications of all research essential to improving the
      quality of human life. Psychologists are positioned to "give psychology away" to
      all those who can benefit from our wisdom. Psychologists were not there 35 years
      ago when American Psychological Association (APA) President George Miller first
      encouraged us to share our knowledge with the public. The author argues that
      psychology is indeed making a significant difference in people's lives; this
      article provides a sampling of evidence demonstrating how and why psychology
      matters, both in pervasive ways and specific applications. Readers are referred
      to a newly developed APA Web site that documents current operational uses of
      psychological research, theory, and methodology (its creation has been the
      author's primary presidential initiative): www.psychologymatters.org.

PMID- 15511123
TI  - Gold Medal Award for Life Achievement in the Practice of Psychology.

PMID- 15511124
TI  - Gold Medal Award for Life Achievement in Psychology in the Public Interest.

PMID- 15511125
TI  - Gold Medal Award for Life Achievement in the Science of Psychology.

PMID- 15511126
TI  - Charles L. Brewer Award for Distinguished Teaching in Psychology.

PMID- 15511128
TI  - Potential adjunctive therapies in adolescents with type 1 diabetes mellitus.
AB  - Appropriate insulin therapy is central to the management of all individuals with
      type 1 diabetes mellitus. The potential role of adjunctive therapy in type 1
      diabetes is to improve insulin action, and facilitate the ability of all
      individuals with type 1 diabetes to achieve and maintain 'better' metabolic
      control. The landmark clinical trial in type 1 diabetes is the Diabetes Control
      and Complications Trial (DCCT). The DCCT showed that there is no threshold below
      which a reduction in glycemia would not provide further benefit against diabetes
      related microvascular complications. This study in particular provides the
      rationale for attempting to achieve as near normoglycemia as possible. We review
      the use of recognized pharmacologic agents as potential insulin adjunctives in
      children and adolescents with type 1 diabetes. Adjunctive therapies can be
      grouped into the following categories based on their putative mechanism of
      action: enhancement of insulin action (e.g. the biguanides and
      thiazolidinediones), alteration of gastrointestinal nutrient delivery (e.g.
      acarbose and amylin), and other targets of action (e.g. pirenzepine and insulin
      like growth factor-1 [IGF-1], which reduce growth hormone secretion, and glucagon
      like peptide-1, which acts to stimulate insulin secretion). Many of these agents
      have been found to be effective in short-term studies with decreases in
      glycosylated hemoglobin of 0.5-1.0%, lowered postprandial blood glucose levels,
      and decreased daily insulin doses. Adverse effects such as poor gastrointestinal
      tolerability (metformin, acarbose) or potential acceleration of retinopathy (IGF
      1) indicates the need for further studies of efficacy, safety, and patient
      selection before these adjunctive therapies can be widely recommended in type 1
      diabetes.

PMID- 15511129
TI  - Endocannabinoid receptor antagonists: potential for obesity treatment.
AB  - Obesity has been described as a global epidemic. Its increasing prevalence is
      matched by growing costs, not only to the health of the individual, but also to
      the medical services required to treat a range of obesity-related diseases. In
      most instances, obesity is a product of progressively less energetic lifestyles
      and the over-consumption of readily available, palatable, and highly caloric
      foods. Past decades have seen massive investment in the search for effective anti
      obesity therapies, so far with limited success. An important part of the process
      of developing new pharmacologic treatments for obesity lies in improving our
      understanding of the psychologic and physiologic processes that govern appetite
      and bodyweight regulation. Recent discoveries concerning the endogenous
      cannabinoids are beginning to give greater insight into these processes. Current
      research indicates that endocannabinoids may be key to the appetitive and
      consummatory aspects of eating motivation, possibly mediating the craving for and
      enjoyment of the most desired, most fattening foods. Additionally,
      endocannabinoids appear to modulate central and peripheral processes associated
      with fat and glucose metabolism. Selective cannabinoid receptor antagonists have
      been shown to suppress the motivation to eat, and preferentially reduce the
      consumption of palatable, energy-dense foods. Additionally, these agents act to
      reduce adiposity through metabolic mechanisms that are independent of changes in
      food intake. Given the current state of evidence, we conclude that the
      endocannabinoids represent an exciting target for new anti-obesity therapies.

PMID- 15511130
TI  - Combining bisphosphonates with hormone therapy for postmenopausal osteoporosis.
AB  - Osteoporosis affects many women after menopause. It is a major health problem, as
      fragility fractures create significant morbidity in this population, especially
      with advancing age. Available therapies include estrogens, selective estrogen
      receptor modulators, bisphosphonates, and calcitonin. They all inhibit bone
      resorption, although through different mechanisms. Several combinations of these
      agents have been studied in order to determine their effectiveness in comparison
      with monotherapy. We reviewed eight prospective randomized clinical trials of
      hormone therapies combined with bisphosphonates (etidronate, alendronate, and
      risedronate) and one study of a selective estrogen receptor modulator
      (raloxifene) in combination with a bisphosphonate (alendronate). Bone mineral
      density change at the lumbar spine was the primary endpoint of all the studies,
      with one or more measurements of the bone density at the femur as secondary
      endpoints. None of the studies had the statistical power to determine the
      relative reduction in fracture risk. All the studies reported greater increases
      in bone mineral density in patients treated with combination therapies as opposed
      to single agents. The bone turnover markers were also suppressed to a greater
      degree in the combination treatment groups, remaining however within normal
      premenopausal ranges. Four studies reported bone histomorphometry data,
      indicating no impairment of bone quality by combination therapies. The
      combination treatments were well tolerated in all the trials and the
      discontinuation rates did not vary among the groups. However, most patients will
      not require combination therapy. Combining bisphosphonates with hormone therapy
      may offer an additional benefit to women who either continue to lose bone mass
      despite taking estrogen or who need estrogen to control postmenopausal symptoms.
      The benefit of adding raloxifene to a bisphosphonate is smaller. However, it may
      be clinically useful if raloxifene reduces the risk of breast cancer.

PMID- 15511131
TI  - Comparative use of urinary and recombinant human chorionic gonadotropins in
      women.
AB  - Human chorionic gonadotropin (hCG) preparations have been widely used as a
      surrogate for the mid-cycle luteinizing hormone (LH) surge for several decades.
      The urinary source of hCG preparations was favored for many years because of the
      easy collection of the starting material. However, the final structure of these
      urinary-derived preparations appears to be quite different from the natural
      placenta product. Furthermore, many disadvantages of these commercial
      preparations have been reported, such as local adverse events and immunologic
      reactions. The recent advent of recombinant DNA technology has now made
      recombinant hCG (r-hCG) available. This new product ensures high purity and batch
      to-batch consistency. The pharmacokinetic and pharmacodynamic profiles of both
      urinary and recombinant preparations are quite similar. In clinical practice,
      several trials have been performed to compare both the efficacy and safety of
      urinary hCG (u-hCG) and r-hCG preparations. Overall, the reported data show that
      r-hCG preparations are at least as effective as u-hCG products in reproducing the
      follicular events surrounding the endogenous LH surge. Moreover, the r-hCG
      products ensure a better hormonal environment during the luteal phase. Finally,
      the overall tolerability of r-hCG preparations has been shown to be much better
      than that of u-hCG preparations. As a consequence, the newly available r-hCG
      preparations offer the first opportunity for clinicians to treat anovulatory
      women with a full range of recombinant products.

PMID- 15511132
TI  - Idiopathic or hypogonadal osteoporosis in men: current and future treatment
      options.
AB  - Osteoporosis is being recognized increasingly in men, and represents a
      substantial public health problem. As the male population ages and lives longer,
      the incidence of osteoporotic fractures is expected to increase. The current
      lifetime risk for a fragility fracture is approximately 27% in men aged 50 years
      or more, and will increase further over the next 20 years. A major problem with
      osteoporosis in men is that it continues to be unrecognized, and the majority of
      men with fragility fractures due to osteoporosis are not being treated. A higher
      level of awareness is required amongst both general practitioners and the general
      public that osteoporosis is a treatable condition that can affect men. Secondary
      causes for osteoporosis are more common in men than in women, and require
      rigorous exclusion and treatment. Undiagnosed clinical hypogonadism is a common
      cause of osteoporosis in men, and is readily treatable. The cause of primary
      osteoporosis in men is unknown, but it results in an osteoblast defect. Genetic
      factors are likely to be important. In some but not all men, relative estrogen
      deficiency contributes to rapid rates of age-related bone loss and fractures. An
      adequate calcium intake, regular weight-bearing exercise, and normal vitamin D
      status are all very important, particularly with increasing age. The role of
      testosterone in treating eugonadal men with osteoporosis is currently unclear,
      and larger prospective studies will be required to carefully evaluate the
      benefits and risks of therapy. First-line treatment of osteoporosis in
      hypogonadal or eugonadal men is with bisphosphonates. Alendronate increases bone
      density and reduces vertebral fractures measured using a semiquantitative method
      in eugonadal or hypogonadal men with osteoporosis. In the near future, it is
      likely that subcutaneous human parathyroid hormone (1-34) or teriparatide will
      also be available as an important new anabolic treatment for men with
      osteoporosis. Teriparatide treatment also increases bone density in men.
      Selective estrogen receptor modulating drugs require further evaluation in men,
      but would appear to theoretically benefit men, especially those with low
      estradiol levels. In the future, selective androgen receptor modulating drugs may
      be useful in the prevention and treatment of osteoporosis, and in increasing lean
      body mass in men, without having adverse effects on prostate and breast tissue.

PMID- 15511133
TI  - Menopause, the cardiovascular risk factor homocysteine, and the effects of
      treatment.
AB  - Since the identification of homocysteine (Hcy) as a risk factor for
      cardiovascular disease, it has been the subject of much research. As with other
      cardiovascular risk factors, a gender difference exists for Hcy. Plasma levels
      are lower in women of reproductive age than in men and postmenopausal women. This
      has led to the hypothesis that the increased risk of cardiovascular disease
      documented in postmenopausal women may be related to the increase in Hcy levels.
      Factors affecting total plasma levels of Hcy include genetic factors, nutritional
      factors, and lifestyle. Many studies appear to support the ability of estrogen
      replacement therapy to significantly lower both basal levels of Hcy and levels
      following methionine loading. A mean reduction of 10-15% in Hcy levels after 6
      months of hormone therapy has been reported. Similarly, raloxifene and tamoxifen
      and low-dose folic acid administration induce reductions in plasma Hcy levels of
      the same degree observed for hormone therapy. The reduction occurs after a few
      months of therapy and is sustained, suggesting the potential for cardioprotective
      effects. Although there is a positive effect of estrogen therapy and hormone
      therapy on Hcy levels, recent studies do not recommend the use of estrogen or
      hormone replacement therapy for the primary or secondary prevention of
      cardiovascular disease. Further research is therefore needed to identify
      strategies to maximize the efficacy of hormone replacement therapy, while
      minimizing the risks.

PMID- 15511134
TI  - Formally exact quantization condition for nonrelativistic quantum systems.
AB  - Based on the standard transfer matrix, a formally exact quantization condition
      for arbitrary potentials, which outflanks and unifies the historical approaches,
      is derived. It can be used to find the exact bound-state energy eigenvalues of
      the quantum system without solving an equation of motion for the system wave
      functions.

PMID- 15511135
TI  - The Kawasaki identity and the Fluctuation Theorem.
AB  - In this paper we show that the Fluctuation Theorem of Evans and Searles [D. J.
      Evans, D. J. Searles, Phys. Rev. E 50, 1645 (1994)] implies that the Kawasaki
      function exp(-Omega(t)) is unity for all time t. We confirm this relationship
      using experimental data obtained using optical tweezers, and show that the
      Kawasaki function is a valuable diagnostic tool.

PMID- 15511136
TI  - Calculation of single-beam two-photon absorption rate of lanthanides: effective
      operator method and perturbative expansion.
AB  - Perturbative contributions to single-beam two-photon transition rates may be
      divided into two types. The first, involving low-energy intermediate states,
      require a high-order perturbation treatment, or an exact diagonalization. The
      other, involving high-energy intermediate states, only require a low-order
      perturbation treatment. We show how to partition the effective transition
      operator into two terms, corresponding to these two types, in such a way that a
      many-body perturbation expansion may be generated that obeys the linked cluster
      theorem and has a simple diagrammatic representation.

PMID- 15511137
TI  - Effect of the Perdew-Zunger self-interaction correction on the thermochemical
      performance of approximate density functionals.
AB  - The Perdew-Zunger self-interaction-corrected density functional theory (SIC-DFT)
      was implemented self-consistently using a quasi-Newton direct minimization
      method. We calculated SIC-DFT energies for a number of atoms and molecules using
      various approximate density functionals, including hybrids. Self-interaction
      errors (SIE) of these functionals were compared and analyzed in terms of
      contributions from valence and core orbitals. We also calculated enthalpies of
      formation of the standard G2-1 set of 55 molecules and found that self
      interaction-correction (SIC) improves agreement with experiment only for the LSDA
      functional, while all other functionals show worse performance upon introducing
      SIC. This is the first systematic study of the effect of SIC on thermochemical
      properties. We found no direct connection between the magnitude of the SIE
      contained in a functional and its performance for thermochemistry. Approximate
      functionals with large self-interaction errors can accurately reproduce
      enthalpies of formation. Our results do not support the popular belief that a
      smaller SIE of hybrid functionals is the main reason for their higher accuracy.

PMID- 15511138
TI  - A theoretical study of the excited states of CrH: potential energies, transition
      moments, and lifetimes.
AB  - Ab initio calculations of low-lying electronic states of CrH are presented,
      including potential energies, dipole and transition dipole moment (TDM)
      functions, and radiative lifetimes for X (6)Sigma(+), A (6)Sigma(+), 3
      (6)Sigma(+), 1 (6)Pi, 2 (6)Pi, 3 (6)Pi, and (6)Delta. Calculation of dynamic
      correlation effects was performed using the multistate complete active space
      second-order perturbation method, based on state-averaged complete active space
      self-consistent-field reference wave functions obtained with seven active
      electrons in an active space of 16 molecular orbitals. A relativistic atomic
      natural orbital-type basis set from the MOLCAS library was used for Cr. Good
      agreement is found between the current calculations and experiment for the lowest
      two (6)Sigma(+) states, the only states for which spectroscopic data are
      available. Potential curves for the 3 (6)Sigma(+) and 2 (6)Pi states are
      complicated by avoided crossings with higher states of the same symmetry, thus
      resulting in double-well structures for these two states. The measured bandhead
      T(0)=27 181 cm(-1), previously assigned to a (6)Pi<--X (6)Sigma(+) transition, is
      close to our value of T(0)=28 434 cm(-1) for the 2 (6)Pi state. We tentatively
      assign the ultraviolet band found experimentally at 30 386 cm(-1) to the 3 (6)Pi<
      -X (6)Sigma(+) transition for which the computed value is 29 660 cm(-1). The A
      (6)Sigma(+)<--X (6)Sigma(+) TDM and A (6)Sigma(+) lifetimes are found to be in
      reasonable agreement with previous calculations.

PMID- 15511139
TI  - Mass-independent isotope effect in the earliest processed solids in the solar
      system: a possible chemical mechanism.
AB  - A major constraint is described for a possible chemical origin for the "mass
      independent" oxygen isotope phenomenon in calcium-aluminum rich inclusions (CAIs)
      in meteorites at high temperatures ( approximately 1500-2000 K). A symmetry-based
      dynamical eta effect is postulated for O atom-monoxide recombination on the
      surface of growing CAIs. It is the surface analog of the volume-based eta effect
      occurring in a similar phenomenon for ozone in the gas phase [Y. Q. Gao, W. C.
      Chen, and R. A. Marcus, J. Chem. Phys. 117, 1536 (2002), and references cited
      therein]: In the growth of CAI grains an equilibrium is postulated between
      adsorbed species XO (ads)+O (ads) <==>XO*(2)(ads), where XO*(2)(ads) is a
      vibrationally excited adsorbed dioxide molecule and X can be Si, Al, Ti, or other
      metals and can be C for minerals less refractory than the CAIs. The surface of a
      growing grain has an entropic effect of many order of magnitude on the position
      of this monoxide-dioxide equilibrium relative to its volume-based position by
      acting as a concentrator. The volume-based eta effect for ozone in the earlier
      study is not applicable to gas phase precursors of CAIs, due to the rarity of
      three-body recombination collisions at very low pressures and because of the high
      H(2) and H concentration in solar gas, which reduces gaseous O and gaseous
      dioxides and prevents the latter from acting as storage reservoirs for the two
      heavier oxygen isotopes. A surface eta effect yields XO*(2)(ads) that is mass
      independently rich in (17)O and (18)O, and yields XO (ads)+O (ads) that is mass
      independently poor in the two heavier oxygen isotopes. When the XO*(2)(ads) is
      deactivated by vibrational energy loss to the grain, it has only one subsequent
      fate, evaporation, and so undergoes no further isotopic fractionation. After
      evaporation the XO(2) again has only one fate, which is to react rapidly with H
      and ultimately form (16)O-poor H(2)O. The other species, O (ads)+XO (ads), are
      (16)O rich and react with Ca (ads) and other adsorbed metal atoms or metallic
      monoxides to form CAIs. The latter are thereby mass-independently poor in (17)O
      and (18)O. Some O (ads) used to form the minerals are necessarily in excess of
      the XO (ads), because of the stoichiometry of the mineral, and modify the
      fractionation pattern. This effect is incorporated into the mechanistic and
      mathematical scheme. A merit of this chemical mechanism for the oxygen isotope
      anomaly is that only one oxygen reservoir is required in the solar nebula. It
      also does not require a sequestering of intermediate products which could undergo
      isotopic exchange, hence undoing the original isotopic fractionations. The gas
      phase source of adsorbed O atoms in this environment is either O or H(2)O. As
      inferred from data on the evaporation of Mg(2)SiO(4) taken as an example, the
      source of O (ads) is primarily H(2)O rather than O and is accompanied by the
      evolution of H(2). Nonisotopic kinetic experiments can determine more sharply the
      mechanism of condensed phase growth of these minerals. Laboratory tests are
      proposed to test the existence of a surface eta effect on the growing CAI
      surfaces at these high temperatures.

PMID- 15511140
TI  - Structure, stability, and spectra of C9H3, C11H3, and C13H3 radicals.
AB  - Density functional theory has been used to investigate the geometries,
      vibrational frequencies, rotational constants, and dipole moments of the
      C(9)H(3), C(11)H(3), and C(13)H(3) radicals. Vertical electronic transition
      energies of C(9)H(3), C(11)H(3), and C(13)H(3) are calculated by the time
      dependent density functional theory. Present results show that the most stable
      arrangements of C(9)H(3), C(11)H(3), and C(13)H(3) are H(2)C(9)H, H(2)C(11)H, and
      H(2)C(13)H with a C(2v) symmetry, respectively. Such lowest-energy isomers have
      an obvious single and triple bond alternation carbon chain. Their isomers
      HC(4)(HC)C(4)H, HC(4)[C(C(2)H)]C(4)H, and C(C(4)H)(3) are predicted to have
      vibrational frequencies and vertical excitation energies in good agreement with
      experimental observations. HC(4)(HC)C(4)H, HC(4)[C(C(2)H)]C(4)H, and C(C(4)H)(3)
      have similar trigonal structure, which gives rise to the remarkably similar
      spectroscopic features as obtained experimentally. On the basis of present
      calculations, the isomers HC(4)(HC)C(4)H, HC(4)[C(C(2)H)]C(4)H, and C(C(4)H)(3)
      of C(9)H(3), C(11)H(3), and C(13)H(3) radicals are most likely the carriers of
      the observed spectra.

PMID- 15511141
TI  - An Anderson impurity model for efficient sampling of adiabatic potential energy
      surfaces of transition metal complexes.
AB  - We present a model intended for rapid sampling of ground and excited state
      potential energy surfaces for first-row transition metal active sites. The method
      is computationally inexpensive and is suited for dynamics simulations where (1)
      adiabatic states are required "on-the-fly" and (2) the primary source of the
      electronic coupling between the diabatic states is the perturbative spin-orbit
      interaction among the 3d electrons. The model Hamiltonian we develop is a variant
      of the Anderson impurity model and achieves efficiency through a physically
      motivated basis set reduction based on the large value of the d-d Coulomb
      interaction U(d) and a Lanczos matrix diagonalization routine to solve for
      eigenvalues. The model parameters are constrained by fits to the partial density
      of states obtained from ab initio density functional theory calculations. For a
      particular application of our model we focus on electron transfer occurring
      between cobalt ions solvated by ammonium, incorporating configuration interaction
      between multiplet states for both metal ions. We demonstrate the capability of
      the method to efficiently calculate adiabatic potential energy surfaces and the
      electronic coupling factor we have calculated compares well to previous
      calculations and experiment. (

PMID- 15511142
TI  - Observation of Au2H- impurity in pure gold clusters and implications for the
      anomalous Au-Au distances in gold nanowires.
AB  - Au(2)H(-) was recognized and confirmed as a minor contamination to typical
      photoelectron spectra of Au(2) (-), produced by laser vaporization of a pure Au
      target using an ultrahigh purity helium carrier gas. The hydrogen source was
      shown to be from trace H impurities present in the bulk gold target. Carefully
      designed experiments using H(2)- and D(2)-seeded helium carrier gas were used to
      study the electronic structure of Au(2)H(-) and Au(2)D(-) using photoelectron
      spectroscopy and density functional calculations. Well-resolved photoelectron
      spectra with vibrational resolution were obtained for Au(2)H(-) and Au(2)D(-).
      Two isomers were observed both experimentally and theoretically. The ground state
      of Au(2)H(-) turned out to be linear with a terminal H atom [Au-Au-H](-)
      ((1)A(1),C(infinity v)), whereas a linear [Au-H-Au](-) ((1)A(1),D(infinity h))
      structure with a bridging H atom was found to be a minor isomer 0.6 eV higher in
      energy. Calculated electron detachment energies for both isomers agree well with
      the experimental spectra, confirming their existence in the cluster beam. The
      observation and confirmation of H impurity in pure gold clusters and the 3.44 A
      Au-Au distance in the [Au-H-Au](-) isomer presented in the current work provide
      indirect experimental evidence that the anomalous 3.6 A Au-Au distances observed
      in gold nanowires is due to an "invisible" hydrogen impurity atom.

PMID- 15511143
TI  - Infrared depletion spectra of 2-aminopyridine2-pyridone, a Watson-Crick mimic of
      adenine.uracil.
AB  - The 2-aminopyridine2-pyridone (2AP2PY) dimer is linked by N-H...O=C and N-H...N
      hydrogen bonds, providing a model for the Watson-Crick hydrogen bond
      configuration of the adenine.thymine and adenine.uracil nucleobase pairs. Mass
      specific infrared spectra of 2AP2PY and its seven N-H deuterated isotopomers have
      been measured between 2550 and 3650 cm(-1) by IR laser depletion combined with UV
      two-color resonant two-photon ionization. The 2PY amide N-H stretch is a very
      intense band spread over the range 2700-3000 cm(-1) due to large anharmonic
      couplings. It is shifted to lower frequency by 710 cm(-1) or approximately 20%
      upon H bonding to 2AP. On the 2AP moiety, the "bound" amino N-H stretch gives
      rise to a sharp band at 3140 cm(-1), which is downshifted by 354 cm(-1) or
      approximately 10% upon H bonding to 2PY. The amino group "free" N-H stretch and
      the H-N-H bend overtone are sharp bands at approximately 3530 cm(-1) and 3320 cm(
      1). Ab initio structures and harmonic vibrations were calculated at the Hartree
      Fock level and with the PW91 and B3LYP density functionals. The PW91/6
      311++G(d,p) method provides excellent predictions for the frequencies and IR
      intensities of all the isotopomers.

PMID- 15511144
TI  - Normal Auger spectra of Br in alkali bromide molecules.
AB  - Molecular Auger electron spectra following the bromine 3d ionization in gas-phase
      alkali bromides and in HBr were studied both experimentally and theoretically.
      The AES for HBr and CsBr were measured using photoexcitation, and for LiBr, NaBr,
      and KBr by using electron impact. These results are compared with the theoretical
      spectra from nonrelativistic ab initio calculations and one-center approximation
      and with the spectra of Br(-), computed with the multiconfiguration Dirac-Fock
      method.

PMID- 15511145
TI  - One- and two-photon absorption of three-coordinate compounds with different
      centers (B,Al,N) and a 2,2'-dipyridylnitrogen functional group.
AB  - A series of three-coordinate octupolar compounds with varied centers (boron,
      aluminum, and nitrogen), which exhibit very large effective two-photon absorption
      cross sections have been theoretically studied. The ground state geometries and
      electronic structures are obtained using the density functional theory with the
      B3LYP functional and 6-31G(d) basis set, and the results are comparable to the
      available experimental determinations. Based on the correct geometrical and
      electronic structures, the one- and two-photon absorptions are predicted by the
      ZINDO-SOS method. Among these compounds, the boron (B) and aluminum (Al) centers
      act as acceptors, while the nitrogen center acts as donor according to the net
      charge changes during the excitation. It is found that (i) the compounds with
      boron and aluminum centers show two large two-photon absorption peaks, while the
      molecule with nitrogen center show only one two-photon absorption peak; (ii) the
      cross sections of the molecules with B or Al as centers are larger than that of
      the molecule with nitrogen as center; furthermore, the two-photon absorption
      cross section of the molecule with Al center is larger than that of the molecule
      with B center, from this point of view, our theoretical prediction provides for
      the experiment a good new candidate with large two-photon absorption cross
      section for further research; (iii) lengthening the conjugation bridge by
      inserting a benzene ring on the organoborane compounds (forming the investigated
      molecule B-2) enhances the two-photon absorption cross section, and keeping good
      transparency at the same time.

PMID- 15511146
TI  - Potential energy surface, bound states, and rotational inelastic cross sections
      of the He-CH4 system: a theoretical investigation.
AB  - We determined two potential energy surfaces (PES) for the He-CH(4) system by
      means of MP4 and Valence Bond (VB) calculations. The MP4 potential is similar to
      the one commonly adopted for this system [U. Buck, K. H. Kohl, A. Kolhase, M.
      Faubel, and U. Staemmler, Mol. Phys. 55, 1255 (1985)], while the VB PES is
      slightly more attractive. To evaluate the reliability of these potentials, we
      investigated the scattering properties by performing close coupling calculations,
      and concluded that: (i) the available experimental data do not permit the ranking
      among the PES considered; (ii) some theoretical predictions differ considerably
      from the experimental data, and these discrepancies cannot entirely be ascribed
      to the inaccuracy of the ab initio calculations; (iii) the scattering properties
      at low energy might discriminate between the MP4 and VB potentials.

PMID- 15511147
TI  - Experimental and theoretical investigations of rate coefficients of the reaction
      S(3P)+O2 in the temperature range 298-878 K.
AB  - Rate coefficients of the reaction S+O(2) with Ar under 50 Torr in the temperature
      range 298-878 K were determined with the laser photolysis technique. S atoms were
      generated by photolysis of OCS with a KrF excimer laser at 248 nm; their
      concentration was monitored via resonance fluorescence excited by atomic emission
      of S produced from microwave-discharged SO(2). Our measurements show that k(298
      K)=(1.92+/-0.29)x10(-12) cm(3) molecule(-1) s(-1), in satisfactory agreement with
      previous reports. New data determined for 505-878 K show non-Arrhenius behavior;
      combining our results with data reported at high temperatures, we derive an
      expression k(T)=(9.02+/-0.27)x10(-19)T(2.11+/-0.15) exp[(730+/-120)/T] cm(3)
      molecule(-1) s(-1) for 298< or =T< or =3460 K. Theoretical calculations at the
      G2M (RCC2) level, using geometries optimized with the B3LYP/6-311+G(3df) method,
      yield energies of transition states and products relative to those of the
      reactants. Rate coefficients predicted with multichannel RRKM calculations agree
      satisfactorily with experimental observations; the reaction channel via SOO(1A')
      dominates at T<500 K, whereas channels involving formation of SOO(3A") followed
      by isomerization to SO(2) before dissociation, and formation of SOO(1A") followed
      by direct dissociation, become important at high temperatures, accounting for the
      observed rapid increase in rate coefficient.

PMID- 15511148
TI  - Potential energy curves of diatomic molecular ions from high-resolution
      photoelectron spectra. II. The first six electronic states of Xe2 +.
AB  - The pulsed-field-ionization zero-kinetic-energy photoelectron spectrum of Xe(2)
      has been measured between 90 000 and 109 000 cm(-1) following single-photon
      excitation from the ground neutral state. Transitions to five of the six low
      lying electronic states of Xe(2) (+) could be observed. Whereas extensive
      vibrational progressions were observed for the X0(g) (+)-->I(1/2u), I(3/2g), and
      II(1/2u) photoelectron transitions, only the lowest vibrational levels of the
      I(3/2u) and II(1/2g) states could be detected. Unambiguous assignments of the
      vibrational quantum numbers were derived from the analysis of the isotopic shifts
      of the vibrational bands and of the intensity distribution and from the modeling
      of the potential energy curves. Analytical potential energy curves of
      spectroscopic accuracy (i.e., approximately 1 meV) were determined for all six
      low-lying electronic states using a global model, which includes the first
      (charge-induced dipole, proportional to 1/R(4)) member of the long-range
      interaction series and treats the spin-orbit interaction explicitly. The
      assumption of an R-independent spin-orbit coupling constant was tested and found
      to be an excellent approximation.

PMID- 15511149
TI  - Organo-noble-gas hydride compounds HKrCCH, HXeCCH, HXeCC, and HXeCCXeH: formation
      mechanisms and effect of 13C isotope substitution on the vibrational properties.
AB  - We investigate the formation mechanism of HXeCCXeH in a Xe matrix. Our
      experimental results show that the HXeCCXeH molecules are formed in the secondary
      reactions involving HXeCC radicals. The experimental data on the formation of
      HXeCCXeH is fully explained based on the model involving the HXeCC+Xe+H-
      >HXeCCXeH reaction. This reaction is the first case when a noble-gas hydride
      molecule is formed from another noble-gas molecule. In addition, we investigate
      the (12)C/(13)C isotope effect on the vibrational properties of organo-noble-gas
      hydrides (HKrCCH, HXeCCH, HXeCC, and HXeCCXeH) in noble-gas matrixes. The present
      experimental results and ab initio calculations on carbon isotope shifts of the
      vibrational modes support the previous assignments of these molecules. Upon (12)C
      to (13)C isotope substitution, we observed a pronounced effect on the H-Kr
      stretching mode of HKrCCH (downshift of 1.0-3.6 cm(-1), depending on the matrix
      site) and a small anomalous shift (+0.1 cm(-1)) of the H-Xe stretching mode of
      HXeCCH and HXeCCXeH.

PMID- 15511150
TI  - A first principles study on the solvation and structure of SO4 2- (H2O)n, n=6-12.
AB  - The structures of hydrated sulfate clusters, SO(4) (2-)(H(2)O)(n) with n=6-12,
      are obtained by density functional theory calculations. For SO(4) (2
      )(H(2)O)(12), two structures with symmetric distribution of H(2)O molecules
      around the sulfate group are favored in energy. The structures for the smaller
      clusters, SO(4) (2-)(H(2)O)(n) with n=6-11, are obtained by taking away one H(2)O
      molecule successively from the two symmetric SO(4) (2-)(H(2)O)(12) isomers. The
      hydrogen bonding between the sulfate O atoms and H(2)O molecules are strong. So
      are the hydrogen bonds among H(2)O molecules, which are facilitated by the
      structure of the polyatomic sulfate group. The solvation energy is quite large
      (often exceeding 15 kcal/mol). The patterns for structural and energy changes as
      the cluster size increases are very different from the well studied hydrated
      halide ions, although the competition between solute-solvent and solvent-solvent
      interactions is again an important factor. Ab initio molecular dynamics
      simulations also show "crowding" effects in the first solvation of SO(4) (2
      )(H(2)O)(12) at raised temperature.

PMID- 15511151
TI  - The mechanism of proton exchange: guided ion beam studies of the reactions,
      H(H2O)n+ (n=1-4)+D2O and D(D2O)n+ (n=1-4)+H2O.
AB  - Reactions of protonated water clusters, H(H(2)O)(n) (+) (n=1-4) with D(2)O and
      their "mirror" reactions, D(D(2)O)(n) (+) (n=1-4) with H(2)O, are studied using
      guided-ion beam mass spectrometry. Absolute reaction cross sections are
      determined as a function of collision energy from thermal energy to over 10 eV.
      At low collision energies, we observe reactions in which H(2)O and D(2)O
      molecules are interchanged and reactions where H-D exchange has occurred. As the
      collision energy is increased, the H-D exchange products decrease and the water
      exchange products become dominant. At high collision energies, processes in which
      one or more water molecules are lost from the reactant ions become important,
      with simple collision-induced dissociation processes, i.e., those without H-D
      exchange, being dominant. Threshold energies of endothermic channels are measured
      and used to determine binding energies of the proton bound complexes, which are
      consistent with those determined by thermal equilibrium measurements and previous
      collision-induced dissociation studies. A kinetic scheme that relies only on the
      ratio of isomerization and dissociation rate constants successfully accounts for
      the kinetic energy dependence observed in the branching ratios for H-D and water
      exchange products in all systems. Rice-Ramsperger-Kassel-Marcus theory and ab
      initio calculations confirm the feasibility and establish the details of this
      kinetic model.

PMID- 15511152
TI  - Observation of rotamers of m-aminobenzoic acid: zero kinetic energy photoelectron
      and hole-burning resonantly enhanced multiphoton ionization spectroscopy.
AB  - We report studies of supersonically cooled m-aminobenzoic acid using two-color
      resonantly enhanced multiphoton ionization (REMPI) and two-color zero kinetic
      energy (ZEKE) photoelectron spectroscopy. Two conformers have been identified and
      characterized using the hole-burning method in the REMPI experiment. With the aid
      of ab initio and density functional calculations, vibrational modes of the first
      electronically excited state (S(1)) of the neutral species and those of the
      ground state cation (D(0)) have been assigned, and the adiabatic ionization
      potentials have been determined for both conformers. The REMPI spectra are
      dominated by in-plane motions of the substituents and ring deformation modes. A
      propensity of Deltav=0, where Deltav is the change in vibrational quantum number
      from the S(1) to the D(0) state, is observed in the ZEKE spectra. The origin of
      this behavior is discussed in the context of electron back donation from the two
      substituents in the excited state and in the cationic state. Comparisons of these
      results with those of p-aminobenzoic acid will be analyzed.

PMID- 15511153
TI  - Electron and nuclear dynamics of molecular clusters in ultraintense laser fields.
      IV. Coulomb explosion of molecular heteroclusters.
AB  - In this paper we present a theoretical and computational study of the temporal
      dynamics and energetics of Coulomb explosion of (CD4)(n) and (CH4)(n) (n=55-4213)
      molecular heteroclusters in ultraintense (I=10(16)-10(19) W cm(-2)) laser fields,
      addressing the manifestation of electron dynamics, together with nuclear
      energetic and kinematic effects on the heterocluster Coulomb instability. The
      manifestations of the coupling between electron and nuclear dynamics were
      explored by molecular dynamics simulations for these heteroclusters coupled to
      Gaussian laser fields (pulse width tau=25 fs), elucidating outer ionization
      dynamics, nanoplasma screening effects (being significant for I< or =10(17) W cm(
      2)), and the attainment of cluster vertical ionization (CVI) (at I=10(17) W cm(
      2) for cluster radius R(0)< or =31 A). Nuclear kinematic effects on heterocluster
      Coulomb explosion are governed by the kinematic parameter eta=q(C)m(A)/q(A)m(C)
      for (CA(4))(n) clusters (A=H,D), where q(j) and m(j) (j=A,C) are the ionic
      charges and masses. Nonuniform heterocluster Coulomb explosion (eta >1) manifests
      an overrun effect of the light ions relative to the heavy ions, exhibiting the
      expansion of two spatially separated subclusters, with the light ions forming the
      outer subcluster at the outer edge of the spatial distribution. Important
      features of the energetics of heterocluster Coulomb explosion originate from
      energetic triggering effects of the driving of the light ions by the heavy ions
      (C(4+) for I=10(17)-10(18) W cm(-2) and C(6+) for I=10(19) W cm(-2)), as well as
      for kinematic effects. Based on the CVI assumption, scaling laws for the cluster
      size (radius R(0)) dependence of the energetics of uniform Coulomb explosion of
      heteroclusters (eta=1) were derived, with the size dependence of the average
      (E(j,av)) and maximal (E(j,M)) ion energies being E(j,av)=aR(0) (2) and
      E(j,M)=(5a/3)R(0) (2), as well as for the ion energy distributions P(E(j))
      proportional to E(j) (1/2); E(j)< or =E(j,M). These results for uniform Coulomb
      explosion serve as benchmark reference data for the assessment of the effects of
      nonuniform explosion, where the CVI scaling law for the energetics still holds,
      with deviations of the a coefficient, which increase with increasing eta.
      Kinematic effects (for eta>1) result in an isotope effect, predicting the
      enhancement (by 9%-11%) of E(H,av) for Coulomb explosion of (C(4+)H(4) (+))(eta)
      (eta=3) relative to E(D,av) for Coulomb explosion of (C(4+)D(4) (+))(eta)
      (eta=1.5), with the isotope effect being determined by the ratio of the kinematic
      parameters for the pair of Coulomb exploding clusters. Kinematic effects for
      nonuniform explosion also result in a narrow isotope dependent energy
      distribution (of width DeltaE) of the light ions (with DeltaE/E(H,av)
      approximately 0.3 and DeltaE/E(D,av) approximately 0.4), with the distribution
      peaking at the high energy edge, in marked contrast with the uniform explosion
      case. Features of laser-heterocluster interactions were inferred from the
      analyses of the intensity dependent boundary radii (R(0))(I) and the
      corresponding average D+ ion energies (E(D,av))(I), which provide a measure for
      optimization of the cluster size at intensity I for the neutron yield from dd
      nuclear fusion driven by Coulomb explosion (NFDCE) of these heteroclusters. We
      infer on the advantage of deuterium containing heteronuclear clusters, e.g.,
      (CD4)(n) in comparison to homonuclear clusters, e.g., (D2)(n/2), for dd NFDCE,
      where the highly charged heavy ions (e.g., C4+ or C6+) serve as energetic and
      kinematic triggers driving the D+ ions to a high (10-200 keV) energy domain.

PMID- 15511154
TI  - Cluster size effects in core excitons of 1s-excited nitrogen.
AB  - Cluster size effects in core excitons below the N 1s ionization energy of
      nitrogen clusters are reported in the energy regime 405-410 eV. These results are
      compared to the molecular Rydberg states as well as the corresponding bulk
      excitons of condensed nitrogen. The experimental results are assigned using ab
      initio calculations. It is found that the lowest excitons (N 1s-->3ssigma and N
      1s-->3ppi) are blueshifted relative to the molecular Rydberg transitions, whereas
      others (N 1s-->3dpi and N 1s-->4ppi) show a redshift. Results from ab initio
      calculations on (N(2))(13) clearly indicate that the molecular orientation within
      a cluster is critical to the spectral shift, where bulk sites as well as inner-
      and outer-surface sites are characterized by different inner-shell absorption
      energies. These results are compared to the experimental spectra as well as
      previous work on site-selectively excited atomic van der Waals clusters,
      providing an improved spectral assignment of core exciton states in weakly bound
      molecular clusters and the corresponding condensed phase.

PMID- 15511155
TI  - Fourier transform microwave spectroscopy and Fourier transform microwave
      millimeter wave double resonance spectroscopy of the ClOO radical.
AB  - Pure rotational spectra of the ClOO radical for the (35)Cl and (37)Cl isotopomers
      have been observed using Fourier transform microwave and Fourier transform
      microwave-millimeter wave double resonance spectroscopy. The rotational,
      centrifugal, spin-rotation coupling, and hyperfine coupling constants have been
      determined by least-squares fits of the observed transition frequencies. The
      molecular constants indicate that the electronic ground state is 2A". The r(0)
      structure is determined to be r(0)(ClO)=2.075 A, r(0)(OO)=1.227 A, and
      theta;(0)(ClOO)=116.4 degrees . Several highly accurate ab initio calculations
      have also been performed. Some of them turned out to be inaccurate because it is
      necessary to take into account both static and dynamic electronic correlations.
      Only multireference (single and double) configuration interaction calculations
      with large basis sets reproduce the present experimental results. The anharmonic
      force constants obtained by the ab initio calculations are used to determine the
      r(e) structure, r(e)(ClO)=2.084(1) A, r(e)(OO)=1.206(2) A, and
      theta;(e)(ClOO)=115.4(1) degrees . Unique features of the ClOO radical have
      become clear by the present experiment and the ab initio calculations.

PMID- 15511156
TI  - Characterizing the later 3d cyanides: the submillimeter spectrum of CoCN(X 3Phi
      i).
AB  - The pure rotational spectrum of the CoCN radical has been recorded in the
      frequency range 350-500 GHz using direct absorption techniques. This study is the
      first spectroscopic observation of this molecule by any experimental technique.
      Spectra of Co (13)CN have been measured as well. These data indicate that this
      species is linear in its ground electronic state and has the cyanide, as opposed
      to the isocyanide, geometry. The ground state term has been assigned as
      (3)Phi(i), based on the measurement of three spin components (Omega=4, 3, and 2)
      and in analogy to other isovalent cobalt-bearing species. Hyperfine splittings
      resulting from the (59)Co nuclear spin of I=7/2 were observed in every
      transition, each of which exhibited an octet pattern. For the lowest energy spin
      component, Omega=4, vibrational satellite features were also identified arising
      from the first quantum of the Co-C (v(1)=1) stretch and the v(2)=1 and v(2)=2
      quanta of the bending mode, which were split by Renner-Teller interactions. The
      ground state measurements of CoCN were analyzed with a case a(beta) Hamiltonian,
      establishing rotational, fine structure, and hyperfine parameters. The
      vibrational and Co (13)CN spectra for the Omega=4 component were fit as well. An
      r(0) structure was also calculated, providing estimates of the Co-C and C-N bond
      distances, based on the Omega=4 transitions. CoCN is the fourth molecule in the
      3d transition metal series to exhibit the linear cyanide structure, along with
      the Zn, Cu, and Ni analogs. The preference for this geometry, as opposed to the
      isocyanide form, may indicate a greater degree of covalent bonding in these
      species.

PMID- 15511157
TI  - Icosahedral gold cage clusters: M@Au12- (M=V, Nb, and Ta).
AB  - We report the observation and characterization of a series of stable bimetallic
      18-valence-electron clusters containing a highly symmetric 12-atom icosahedral Au
      cage with an encapsulated central heteroatom of Group VB transition metals,
      M@Au(12) (-) (M=V,Nb,Ta). Electronic and structural properties of these clusters
      were probed by anion photoelectron spectroscopy and theoretical calculations.
      Characteristics of the M@Au(12) (-) species include their remarkably high binding
      energies and relatively simple spectral features, which reflect their high
      symmetry and stability. The adiabatic electronic binding energies of M@Au(12) (-)
      were measured to be 3.70+/-0.03, 3.77+/-0.03, and 3.76+/-0.03 eV for M=V, Nb, and
      Ta, respectively. Comparison of density-functional calculations with experimental
      data established the highly symmetric icosahedral structures for the 18-electron
      cluster anions, which may be promising building blocks for cluster-assembled
      nanomaterials in the form of stoichiometric [M@Au(12) (-)]X(+) salts.

PMID- 15511158
TI  - Spectroscopy and reactivity of size-selected Mg+ -ammonia clusters.
AB  - Photodissociation spectra for mass-selected Mg(+)(NH(3))(n) clusters for n=1 to 7
      are reported over the photon energy range from 7000 to 38 500 cm(-1). The singly
      solvated cluster, which dissociates primarily via a N-H bond cleavage, exhibits a
      resolved vibrational structure corresponding to two progressions in the
      intracluster Mg(+)-NH(3) modes. The addition of the second, third, and fourth
      solvent molecules results in monotonic redshifts that appear to halt near 8500
      cm(-1), where a sharp feature in the electronic spectrum is correlated with the
      formation of a Mg(+)(NH(3))(4) complex with T(d) symmetry and the closing of the
      first solvation shell. The spectra for the clusters with 5 to 7 solvent molecules
      strongly resemble that for the tetramer, suggesting that these solvent molecules
      occupy a second solvation shell. The wavelength-dependent branching-ratio
      measurements show that increasing the photon energies generally result in the
      loss of additional solvent molecules but that enhancements for a specific solvent
      number loss may reveal special stability for the resultant fragments. The
      majority of the experimental evidence suggests that the decay of these clusters
      occurs via the internal conversion of the initially excited electronic states to
      the ground state, followed by dissociation. In the case of the monomer, the
      selective cleavage of a N-H bond in the solvent suggests that this internal
      conversion process may populate regions of the ground-state surface in the
      vicinity of an insertion complex H-Mg(+)-NH(2), whose existence is predicted by
      ab initio calculations.

PMID- 15511159
TI  - Perturbations in the pure rotational spectrum of CoCl (X 3 Phi i): a
      submillimeter study.
AB  - The millimeter/submillimeter-wave spectrum of the CoCl radical (X (3)Phi(i)) has
      been recorded using direct absorption techniques in the frequency range 340-510
      GHz. This work is the first pure rotational study of this molecule. The radical
      was created by the reaction of Cl(2) with cobalt vapor. Rotational transitions
      arising from the Omega=4, 3, and 2 spin-orbit components of Co(35)Cl have been
      measured, all of which exhibit hyperfine splittings due to the (59)Co nucleus
      (I=7/2). Transitions arising from the Co(37)Cl species were also recorded, as
      well as those originating in the v=1, 2, 3, and 4 vibrational states of both
      isotopomers. The spin-orbit pattern exhibited by the molecule is unusual, with
      the Omega=3 component significantly shifted relative to the other spin
      components. In addition, the regular octet hyperfine splittings become distorted
      above a certain J value for the Omega=3 transitions only. These effects suggest
      that the molecule is highly perturbed in its ground state, most likely a result
      of second-order spin-orbit mixing with a nearby isoconfigurational (1)Phi(3)
      state. The complete data set for Co(35)Cl and Co(37)Cl were fit successfully with
      a case (a) Hamiltonian but required a large negative spin-spin constant of
      lambda=-7196 GHz and higher order centrifugal distortion corrections to the
      rotational, spin-orbit, spin-spin, and hyperfine terms. The value of the spin
      spin constant suggests that the Omega=3 component is shifted to higher energy and
      lies near the Omega=2 sublevel. The hyperfine parameters are consistent with a
      delta(3)pi(3) electron configuration and indicate that CoCl is more covalent than
      CoF.

PMID- 15511160
TI  - On the interatomic Coulombic decay in the Ne dimer.
AB  - The interatomic Coulombic decay (ICD) in the Ne dimer is discussed in view of the
      recent experimental results. The ICD electron spectrum and the kinetic energy
      release of the Ne+ fragments resulting after Coulomb explosion of Ne2 (2+) are
      computed and compared to the measured ones. A very good agreement is found,
      confirming the dynamics predicted for this decay mechanism. The effect of the
      temperature on the electron spectrum is briefly investigated.

PMID- 15511161
TI  - Comparison of the dehalogenation of polyhalomethanes and production of strong
      acids in aqueous and salt (NaCl) water environments: Ultraviolet photolysis of
      CH(2)I(2).
AB  - The ultraviolet photolysis of CH(2)I(2) was studied in water and salt water
      solutions using photochemistry and picosecond time-resolved resonance Raman
      spectroscopy. Photolysis in both types of environments produces mainly
      CH(2)(OH)(2) and HI products. However, photolysis of CH(2)I(2) in salt water
      leads to the formation of different products/intermediates (CH(2)ICl and Cl(2) (
      )) not observed in the absence of salt in aqueous solutions. The amount of
      CH(2)(OH)(2) and HI products appears to decrease after photolysis of CH(2)I(2) in
      salt water compared to pure water. We briefly discuss possible implications of
      these results for photolysis of CH(2)I(2) and other polyhalomethanes in sea water
      and other salt aqueous environments compared to nonsalt water solvated
      environments.

PMID- 15511162
TI  - A simple method for the preparation of pseudopure states in nuclear magnetic
      resonance quantum information processing.
AB  - The use of nuclear magnetic resonance (NMR) to carry out quantum information
      processing (QIP) often requires the preparation, transformation, and detection of
      pseudopure states. In our previous work, it was shown that the use of pairs of
      pseudopure states (POPS) as a basis for QIP is very convenient because of the
      simplicity in experimental execution. It is now further demonstrated that the
      product of the NMR spectra corresponding to two sets of POPS that share a common
      pseudopure state has the same peak frequencies as those of the common (single)
      pseudopure state. Examples of applying two different quantum logic gates to a 5
      qubit system are given.

PMID- 15511163
TI  - On the mechanical properties and phase behavior of silica: a simple model based
      on low coordination and strong association.
AB  - We present a simple and computationally efficient classical atomistic model of
      silica in which the silicon and oxygen are simulated as hard spheres with four
      and two association sites, respectively. We have performed isobaric-isothermal
      Monte Carlo simulations to study the mechanical and phase behavior of this model.
      We have investigated solid phase structures of the model corresponding to quartz,
      cristobalite, and coesite, as well as some zeolite structures. For the model
      these phases are mechanically stable and highly incompressible. Ratios of zero
      pressure bulk moduli and thermal expansion coefficients for alpha quartz, alpha
      cristobalite, and coesite are in quite good agreement with experimental values.
      The pressure-temperature phase diagram was constructed and shows three solid
      phases corresponding to cristobalite, quartz, and coesite, as well as a fluid or
      glass phase, behavior qualitatively similar to that seen for silica
      experimentally.

PMID- 15511164
TI  - High pressure-temperature Raman measurements of H2O melting to 22 GPa and 900 K.
AB  - The melting curve of H(2)O has been measured by in situ Raman spectroscopy in an
      externally heated diamond anvil cell up to 22 GPa and 900 K. The Raman-active OH
      stretching bands and the translational modes of H(2)O as well as optical
      observations are used to directly and reliably detect melting in ice VII. The
      observed melting temperatures are higher than previously reported x-ray
      measurements and significantly lower than recent laser-heating determinations.
      However, our results are in accord with earlier optical determinations. The
      frequencies and intensities of the OH-stretching peaks change significantly
      across the melting line while the translational mode disappears altogether in the
      liquid phase. The observed OH-stretching bands of liquid water at high pressure
      are very similar to those obtained in shock-wave Raman measurements.

PMID- 15511165
TI  - Tests for thermodynamic state of water's high-density amorph.
AB  - Analysis of the density and ultrasonic velocity data for water's high-density
      amorph (HDA) far from its formation conditions shows that HDA made by
      pressurizing ice Ih is different from HDA made by pressurizing its low-density
      amorph (LDA), and the density and ultrasonic velocity of HDA depend upon the
      pressure and temperature path used to make it from ice Ih. This seems
      inconsistent with the description of HDA-LDA phase equilibrium. Similar tests may
      be used to clarify the nature of the nonergodic transitions in GeO(2) and SiO(2).

PMID- 15511166
TI  - High density amorphous ices: disordered water towards close packing.
AB  - The structure of amorphous ice under pressure has been studied by molecular
      dynamics at 160 K. The starting low-density phase undergoes significant changes
      as the density increases, and at rho=1.51 g/cm(3) our calculated g(OO)(r) is in
      excellent agreement with in situ neutron diffraction data obtained at 1.8 GPa and
      100 K on very high density amorphous ice made at 150 K. As the system is further
      compressed, in the theoretical simulations, up to rho=1.90 g/cm(3), the
      structural modifications are continuous up to the highest density. The analysis
      of orientational distributions reveals that dense amorphous ice is characterized
      by major distortions of the tetrahedral geometry, and that the pressure
      structural changes, already observed experimentally at lower densities, can be
      interpreted as a trend towards a disordered closed-packed structure.

PMID- 15511167
TI  - Solvent effects on the n-->pi* electronic transition in formaldehyde: a combined
      coupled cluster/molecular dynamics study.
AB  - We present a study of the blueshift of the n-->pi* electronic transition in
      formaldehyde in aqueous solution using a combined coupled cluster/molecular
      mechanics model including mutual polarization effects in the Hamiltonian. In
      addition, we report ground and excited state dipole moments. Configurations are
      generated from molecular dynamics simulations with two different force fields,
      one with and one without an explicit polarization contribution. A statistical
      analysis using 1200 configurations is presented. Effects of explicit polarization
      contributions are found to be significant. It is found that the main difference
      in the effects on the excitation energies arises from the fact that the two force
      fields result in different liquid structures, and thus a different set of
      configurations is generated for the coupled cluster/molecular mechanics
      calculations.

PMID- 15511168
TI  - Potential energy surfaces and dynamics of Ni2+ ion aqueous solution: molecular
      dynamics simulation of the electronic absorption spectrum.
AB  - We develop a model effective Hamiltonian for describing the electronic structures
      of first-row transition metals in aqueous solutions using a quasidegenerate
      perturbation theory. All the states consisting of 3d(n) electronic configurations
      are determined by diagonalizing a small effective Hamiltonian matrix, where
      various intermolecular interaction terms such as the electrostatic, polarization,
      exchange, charge transfer, and three-body interactions are effectively
      incorporated. This model Hamiltonian is applied to constructing the ground and
      triplet excited states potential energy functions of Ni(2+) in aqueous solution,
      based on the ab initio multiconfiguration quasidegenerate perturbation theory
      calculations. We perform molecular dynamics simulation calculations for the
      ground state of Ni(2+) aqueous solution to calculate the electronic absorption
      spectral shape as well as the ground state properties. Agreement between the
      simulation and experimental spectra is satisfactory, indicating that the present
      model can well describe the Ni(2+) excited state potential surfaces in aqueous
      solution.

PMID- 15511169
TI  - Molecular dynamics and theory for the contact values of the radial distribution
      functions of hard-disk fluid mixtures.
AB  - We report molecular dynamics results for the contact values of the radial
      distribution functions of binary additive mixtures of hard disks. The simulation
      data are compared with theoretical predictions from expressions proposed by
      Jenkins and Mancini [J. Appl. Mech. 54, 27 (1987)] and Santos et al. [J. Chem.
      Phys. 117, 5785 (2002)]. Both theories agree quantitatively within a very small
      margin, which renders the former still a very useful and simple tool to work
      with. The latter (higher-order and self-consistent) theory provides a small
      qualitative correction for low densities and is superior especially in the high
      density domain.

PMID- 15511170
TI  - Simple DFT model of clusters embedded in rare gas matrix: trapping sites and
      spectroscopic properties of Na embedded in Ar.
AB  - We present a theoretical model to study the dynamics of metallic clusters
      embedded in a rare gas matrix. We describe the active electrons of the embedded
      cluster using time dependent density functional theory, while the surrounding
      matrix is described in terms of classical molecular dynamics of polarizable
      atoms. The coupling between the cluster and the rare gas atoms is deduced from
      the work of Gross and Spiegelmann [J. Chem. Phys. 108, 4148 (1998)] and
      reformulated explicitly in a simple and efficient density functional form. The
      electron rare gas interaction takes the form of an averaged dipole fluctuation
      term, which retains the van der Waals long range interaction, and a short range
      repulsive pseudopotential, which accounts for the Pauli repulsion of the electron
      by the rare gas atom. We applied our model to Na clusters embedded in Ar matrix.
      For the latter we developed an efficient local pseudopotential, which allows
      studying systems containing more than 10(3) Ar atoms. We show that large systems
      are indeed necessary to account properly for long range polarization of the
      matrix, that competes with the matrix confinement effect. We focus our study on
      Na(2), Na(4), and Na(8). For each system, we have determined the geometry of the
      most favorable trapping site by means of damped molecular dynamics. We present
      the effect of matrix embedding on the optical absorption spectrum. For Na(2), the
      trapping site can be unambiguously identified by comparison of the absorption
      spectrum with experiment. For Na(4) the spectrum of the embedded cluster is
      significantly different from the free cluster spectrum, while for Na(8)
      differences are less pronounced.

PMID- 15511171
TI  - Hydrogen adsorption on zigzag (8,0) boron nitride nanotubes.
AB  - The chemical adsorption of H atoms on an (8,0) zigzag boron nitride nanotube is
      studied using the density functional theory with the supercell method. One to
      four H atoms per 32 B and 32 N are considered. The results show that H atoms
      prefer to adsorb on the top sites of adjacent B and N atoms to form an armchair
      chain along the tube axis. An even-odd oscillation behavior of the adsorption
      energy of H atoms on the tube is found, and the average adsorption energy of even
      H atoms is obviously bigger than that of odd H atoms. The results can be
      understood with the frontier orbital theory. Based on this adsorption behavior,
      several high-symmetric structures of H adsorbed boron nitride nanotubes with 50%
      and 100% coverages are studied. The pairs of lines' pattern with 50% coverage has
      the biggest average adsorption energy per H(2) among the chosen configurations,
      corresponding to approximately 4 wt % hydrogen storage.

PMID- 15511172
TI  - Experimental isotherms of HCl on H2O ice under stratospheric conditions:
      connections between bulk and interfacial thermodynamics.
AB  - The adsorption of HCl on the surface of H(2)O ice has been measured at
      temperatures and pressures relevant to the upper troposphere and lower
      stratosphere. The measured HCl surface coverage is found to be at least 100 times
      lower than currently assumed in models of chlorine catalyzed ozone destruction in
      cold regions of the upper atmosphere. Measurements were conducted in a closed
      system by simultaneous application of surface spectroscopy and gas phase mass
      spectrometry to fully characterize vapor/solid equilibrium. Surface adsorption is
      clearly distinguished from bulk liquid or solid phases. From 180 to 200 K,
      submonolayer adsorption of HCl is well described by a Bragg-Williams modified
      Langmuir model which includes the dissociation of HCl into H(+) and Cl(-) ions.
      Furthermore, adsorption is consistent with two distinct states on the ice
      substrate, one in which the ions only weakly adsorb on separate sites, and
      another where the ions adsorb as an H(+)-Cl(-) pair on a single site with
      adsorption energy comparable to the bulk trihydrate. The number of substrate
      H(2)O molecules per adsorption site is also consistent with the stoichiometry of
      bulk hydrates under these conditions. The ionic states exist in equilibrium, and
      the total adsorption energy is a function of the relative population of both
      states. These observations and model provide a quantitative connection between
      the thermodynamics of the bulk and interfacial phases of HCl/H(2)O, and represent
      a consistent physicochemical model of the equilibrium system.

PMID- 15511173
TI  - Structure and stability of Al13I clusters.
AB  - We have performed density functional calculations for the structures and
      stabilities of Al(13)I at the scalar relativistic pseudopotential and all
      electron levels of theory. The Al(13) moiety in Al(13)I is significantly
      distorted and structurally similar to an Al(13) cation, where the natural
      population is -0.27e for the I atom. Unlike other Al(13)-M (M=H, alkali metals,
      and coinage metals) clusters, a C(s)-ontop structure was found to be the most
      stable form. The Al(13)I cluster has a large Al(13)-I binding energy of 3.11 eV
      and is more stable, as charge transfer to the electronegative I atom is larger.

PMID- 15511174
TI  - Molecular dynamics simulations of amphiphilic graft copolymer molecules at a
      water/air interface.
AB  - Fully atomistic molecular dynamics simulations of amphiphilic graft copolymer
      molecules have been performed at a range of surface concentrations at a water/air
      interface. These simulations are compared to experimental results from a
      corresponding system over a similar range of surface concentrations. Neutron
      reflectivity data calculated from the simulation trajectories agrees well with
      experimentally acquired profiles. In particular, excellent agreement in neutron
      reflectivity is found for lower surface concentration simulations. A simulation
      of a poly(ethylene oxide) (PEO) chain in aqueous solution has also been
      performed. This simulation allows the conformational behavior of the free PEO
      chain and those tethered to the interface in the previous simulations to be
      compared.

PMID- 15511175
TI  - Modeling steps and kinks on the surface of calcite.
AB  - This work presents modeling results on the cleavage face of calcite as well as on
      steps and isolated kinks on this face. We used static lattice energy minimization
      and interatomic potentials fitted to bulk properties. The energy needed to cleave
      a bulk calcite crystal along the [1 0 (-)1 4] plane was calculated to be 0.59 J
      m(-2) in agreement with previous studies using the same potentials. The perfect
      surface reconstructs in the top few atomic layers, but its symmetry corresponds
      to the bulk termination. By contrast, the (1 0 (-)1 4) surface with cleavage
      steps present reconstructs to form a (2 x 1) super cell. This may help explain
      experimental observations of (2 x 1) symmetry on calcite surfaces. The energy
      required to form a monatomic obtuse step is calculated to be 1.3 x 10(-10) J m(
      1) and for the acute step, 2.4 x 10(-10) J m(-1), suggesting that obtuse steps
      dominate on cleaved surfaces. Along the two types of steps, a total of 16 kink
      geometries exist. We calculated kink defect energy with two different approaches:
      one where kink pairs were added onto infinitely long steps and one where kinks
      were placed inside pits on a cleavage surface. Calculations on infinitely long
      steps show that for vacuum conditions, kink pairs possess roughly identical
      formation energy, about 1.2-2.2 eV, so based on energetics one cannot expect
      significant differences in kink site frequency

PMID- 15511176
TI  - Thermodynamics and statistical mechanics of multilayer adsorption.
AB  - The multilayer adsorption models of Brunauer-Emmett-Teller and Guggenheim
      Anderson-de Boer are reconsidered. The relationship between the fitting
      parameters and the physical parameters of the equation is discussed. The
      preexponential factors of the parameters are shown to be in general far different
      from unity, contrary to a widespread use. A thermodynamical derivation
      illuminates the hypothesis on which the multilayer sorption equation is dependent
      and frees it from too restrictive hypothesis usually taken as necessary for its
      validity. Equations are derived for the number fraction of sorption sites
      occupied by different numbers of molecules. The Guggenheim-Anderson-de Boer
      equation is shown to imply incomplete occupation (jamming) of the first sorption
      layer at saturation.

PMID- 15511177
TI  - Infrared spectroscopy of oxygen adsorbed on hydrogen covered Pt(111).
AB  - Using infrared reflection absorption spectroscopy we have investigated how
      preadsorbed hydrogen affects the adsorption of O(2) on the Pt(111) surface at
      temperatures below the onset of the water formation reaction. On the fully
      hydrogen covered surface, Theta(H)=1, O(2) physisorbs at temperatures below 45 K,
      the weakly dipole active internal stretch vibration is observed at 1548 cm(-1).
      Unlike on the clean Pt(111) surface, this adsorption state does not act as a
      precursor for O(2) chemisorption. The physisorbed molecules simply desorb above
      45 K and no chemisorbed O(2) state is populated directly from the gas phase in
      the temperature range 45-90 K. When the surface is approximately half covered,
      Theta(H) approximately 0.4, with preadsorbed hydrogen, O(2) chemisorbs on the
      clean Pt(111) surface regions in the characteristic peroxolike and superoxolike
      states with vibration frequencies around 700 cm(-1) and 870 cm(-1). These values
      correspond to dense O(2) islands which develop already at low O(2) coverages. At
      this hydrogen coverage, we find that the initial sticking probability of
      chemisorbed O(2) is drastically reduced at 90 K and the general uptake also
      proceeds slowly when compared with observations for the clean surface. We suggest
      that this is due to a change in the behavior of the physisorbed O(2) precursor.

PMID- 15511178
TI  - Thermoelectric transport properties in atomic scale conductors.
AB  - The thermoelectric transport properties in atomic scale conductors consisting of
      a Si atom connected by two electrodes are investigated. It is found that both the
      electrical current and the heat current have two contributions, one from the
      voltage and the other from the temperature gradient. The quantities such as the
      Seebeck thermopower and the thermal conductance that characterize the
      thermoelectric transport properties of the tunnel atomic junction are studied
      quantitatively with a first-principles technique within the framework of Landauer
      Buttiker formalism in the linear response regime. A finite thermopower only
      exists in a very narrow range where the energy derivative of the transmission
      function is nonzero. The thermopower anomaly is observed in the tunneling regime
      in this device but this does not violate the thermodynamic law with respect to
      the heat current.

PMID- 15511179
TI  - Polarized absorption of quaterthiophene single crystals.
AB  - Polarized optical spectra of quaterthiophene single crystals are reported over a
      wide spectral range for different planes and angles of incidence corresponding to
      either transverse or mixed longitudinal/transverse wave propagation. From the
      absorbance and reflectance spectra the corresponding absorption coefficients are
      deduced. In the region of the first molecular transition, polarized exciton
      states of Frenkel origin are found to be responsible for a strong optical
      anisotropy and for the modification of the state of polarization during light
      propagation in the crystal. Transmission measurements with crossed polarizer and
      analyzer allow to clearly identify Frenkel replica of the principal transition.

PMID- 15511180
TI  - Kinetics of electron-induced decomposition of CF2Cl2 coadsorbed with water (ice):
      a comparison with CCl4.
AB  - The kinetics of decomposition and subsequent chemistry of adsorbed CF(2)Cl(2),
      activated by low-energy electron irradiation, have been examined and compared
      with CCl(4). These molecules have been adsorbed alone and coadsorbed with water
      ice films of different thicknesses on metal surfaces (Ru; Au) at low temperatures
      (25 K; 100 K). The studies have been performed with temperature programmed
      desorption (TPD), reflection absorption infrared spectroscopy (RAIRS), and x-ray
      photoelectron spectroscopy (XPS). TPD data reveal the efficient decomposition of
      both halocarbon molecules under electron bombardment, which proceeds via
      dissociative electron attachment (DEA) of low-energy secondary electrons. The
      rates of CF(2)Cl(2) and CCl(4) dissociation increase in an H(2)O (D(2)O)
      environment (2-3x), but the increase is smaller than that reported in recent
      literature. The highest initial cross sections for halocarbon decomposition
      coadsorbed with H(2)O, using 180 eV incident electrons, are measured (using TPD)
      to be 1.0+/-0.2 x 10(-15) cm(2) for CF(2)Cl(2) and 2.5+/-0.2 x 10(-15) cm(2) for
      CCl(4). RAIRS and XPS studies confirm the decomposition of halocarbon molecules
      codeposited with water molecules, and provide insights into the irradiation
      products. Electron-induced generation of Cl(-) and F(-) anions in the
      halocarbon/water films and production of H(3)O(+), CO(2), and intermediate
      compounds COF(2) (for CF(2)Cl(2)) and COCl(2), C(2)Cl(4) (for CCl(4)) under
      electron irradiation have been detected using XPS, TPD, and RAIRS. The products
      and the decomposition kinetics are similar to those observed in our recent
      experiments involving x-ray photons as the source of ionizing irradiation.

PMID- 15511181
TI  - A molecular interpretation of vitreous boron oxide dynamics.
AB  - The mobility of vitreous boron oxide is studied by molecular dynamics simulation.
      A polarization model that incorporates induced dipoles arising both from charges
      and from other induced dipoles on atoms with nonzero polarizability is used to
      simulate boron oxide glass at various temperatures above the glass transition
      temperature. Particle mobility is investigated through the calculation of the
      self-intermediate scattering function and the mean-squared displacement. The
      calculations clearly reveal a two-step relaxation with a plateau at intermediate
      times for all investigated temperatures. With respect to atomic species, boron
      atoms are less mobile than oxygen atoms at all temperatures within the plateau
      region. Through analyzing particle trajectories, it is revealed that BO(3) groups
      move as one unit and follow each other in a stringlike manner. Three connected
      BO(3) groups comprise a six-membered boroxol ring, which is shown to move in a
      collective manner, requiring the simultaneous movement of all ring atoms. The
      boroxol ring is observed to be confined, or caged, during the plateau region, and
      jumps to a new location at longer times. This observation is linked to the
      concept of strong versus fragile glass formers and the potential energy
      landscape. In addition to the caging feature, an overshoot or dip occurs in the
      plateau regions of the mean-squared displacement and self-intermediate scattering
      functions respectively. These features are followed by a ringing pattern,
      previously associated with finite size effects in other strong glass formers,
      which persist for the duration of the plateau region. Both features are shown to
      be consistent with the bending of atomic "cages" from the plane of the boroxol
      ring, and arise due to the displacement of atoms from local minimum energy
      configurations.

PMID- 15511182
TI  - Molecular dynamics of transient oil flows in nanopores I: Imbibition speeds for
      single wall carbon nanotubes.
AB  - The way fluids flow into and fill nanotubes is of wide interest; however, there
      are currently no experimental data or validated theoretical models for this
      nanoscale process. We have carried out molecular dynamics simulations of carbon
      nanotubes imbibing oil at an oil/vapor interface at 300 K. We find that the
      smallest (7,7) nanotubes imbibe extremely rapidly (< or =800 m/s) along the inner
      tube surface with the penetration length L a linear function of time. We derive
      expressions for the penetration length L and the velocity of the imbibing oil and
      relate both to the solid-fluid surface tensions and interfacial friction. The
      imbibition of oil by nanotubes is contrasted with the wetting of their external
      surfaces and that of planar surfaces. In all cases the appropriate surface
      tensions can be correlated with the minimum of the oil-molecule wall potential
      providing a means of predicting the internal and external wetting behavior of
      nanotubes.

PMID- 15511183
TI  - Collisional line shapes for low frequency vibrations of adsorbates on a metal
      surface.
AB  - The dynamics of atoms or molecules adsorbed on a metal surface, and excited by
      collisions with an atomic beam, are treated within a theory that includes energy
      dissipation into lattice vibrations by means of a frequency and temperature
      dependent friction function. The theory provides dynamic structure factors for
      energy transfer derived from collisional time correlation functions. It describes
      the relaxation of a vibrationally excited atom or molecule within a model of a
      damped quantum harmonic oscillator bilinearly coupled to a bath of lattice
      oscillators. The collisional time correlation function is generalized to include
      friction effects and is applied to the vibrational relaxation of the frustrated
      translation mode of Na adsorbed on a Cu(001) surface, CO on Cu(001), and CO on
      Pt(111), following excitation by collisions with He atoms. Results for the
      frequency shift and width of line shapes versus surface temperature are in very
      good agreement with experimental measurements of inelastic He atom scattering.
      Our interpretation of the experimental results provides insight on the relative
      role of phonon versus electron-hole relaxation.

PMID- 15511184
TI  - Ionization and solvation of HCl adsorbed on the D2O-ice surface.
AB  - The interaction of HCl with the D(2)O-ice surface has been investigated in the
      temperature range 15-200 K by utilizing time-of-flight secondary ion mass
      spectroscopy, temperature-programmed desorption, and x-ray photoelectron
      spectroscopy. The intensities of sputtered H(+)(D(2)O) and Cl(-) ions (the H(+)
      ions) are increased (decreased) markedly above 40 K due to the hydrogen bond
      formation between the HCl and D(2)O molecules. The HCl molecules which form ionic
      hydrates undergo H/D exchange at 110-140 K and a considerable fraction of them
      dissolves into the bulk above 140 K. The neutral hydrates of HCl should coexist
      as evidenced by the desorption of HCl above 170 K. They are incorporated
      completely in the D(2)O layer up to 140 K. The HCl molecules embedded in the
      thick D(2)O layer dissolve into the bulk, and the ionic hydrate tends to
      segregate to the surface above 150 K.

PMID- 15511185
TI  - Extended version of the van der Waals capillarity theory.
AB  - An extended version of the van der Waals capillarity theory describing the liquid
      vapor interface in the temperature range from the triple to the critical point is
      suggested. A model functional of thermodynamic potential for a two-phase Lennard
      Jones system taking into account the effect of the highest degree terms of
      gradient expansion has been constructed. The identity of the thermodynamic and
      the mechanical definition of Tolman's length has been proved in the framework of
      the adopted form of functional. The properties of nuclei of the liquid and the
      vapor phase are described. The paper determines: the work of formation of a
      nucleus, density profiles, size dependences of the surface tension, and the
      parameter delta in the Gibbs-Tolman-Koenig-Buff equation.

PMID- 15511186
TI  - High T(g) photorefractive polymers: influence of the chromophores' beta tensor.
AB  - In this paper we study the effect of the chromophores' beta tensor active
      components on the diffraction efficiency of a high T(g) photorefractive polymer.
      In particular, we study the two simplest structures with nonvanishing dipole
      moment, the one-dimension push-pull systems, and the Lambda-shaped chromophores.
      We have developed a model that relate the diffraction efficiency expression with
      experimental conditions and microscopic properties of the molecules used. Using
      this model we determine the optimum experimental conditions for both kinds of
      chromophores and the criteria for the design of chromophores with improved
      microscopic properties. The model was also used to evaluate the diffraction
      efficiency of the chromophore Disperse Red 1 (DR1) with a good agreement with
      experimental data present in bibliography, and of other chromophores selected
      with the criteria derived from the model, using quantum mechanical calculations
      to obtain the microscopic properties. Using the designed chromophores diffraction
      efficiencies more than one order of magnitude higher than that calculated for DR1
      with the experimental conditions has been obtained in simulations. These
      chromophores also exhibit a low dependency of eta on the electric field
      polarization in contrast to the DR1 or the low T(g) photoreactive materials.

PMID- 15511187
TI  - Some issues on the calculation of interfacial properties by molecular simulation.
AB  - Some of the pitfalls that may befall molecular simulations of interfaces are
      discussed. They are all related to the calculation of the pressure tensor
      profiles, which are needed in order to compute surface tensions. We focus on
      three controversial points: (1) the calculation of the pressure tensor profiles
      for polyatomic systems, in particular, when the SHAKE algorithm is employed, (2)
      the addition of long-range corrections to compensate the truncation of the
      potential, and (3) the importance of including adequate error intervals with the
      results. Most of the conclusions are general, but some specifically apply to
      multiple site molecular-dynamics simulations.

PMID- 15511188
TI  - Simulation of electric double layers with multivalent counterions: ion size
      effect.
AB  - In this paper, the structure of the electric double layer in the presence of
      (mostly) multivalent counterions is investigated through Monte Carlo simulations.
      Unlike previous similar studies addressing this matter, the difference of this
      study lies in the use of realistic hydrated ion sizes. Additionally, two
      different methods for calculating energies in the Metropolis algorithm are
      applied. The obtained results show that the conclusions of preceding papers must
      be revised. In particular, our simulations suggest the existence of certain ion
      layering effects at high surface charge densities, which are not accounted for by
      integral equation theories in the case of divalent counterions. These layering
      effects could justify why the overcharging phenomena due to ion size correlations
      are hardly observable in real colloids with divalent counterions. The existence
      of charge inversion due to ion size correlations (and without requiring specific
      counterion adsorption) is probed for trivalent counterions. Moreover, the
      hypernetted-chain/mean-spherical-approximation is tested under conditions not
      studied yet.

PMID- 15511189
TI  - Influence of a depletion interaction on dynamical heterogeneity in a dense quasi
      two-dimensional colloid liquid.
AB  - We report the results of digital video microscopy studies of the large particle
      displacements in a quasi-two-dimensional binary mixture of large (L) and small
      (S) colloid particles with diameter ratio sigma(L)/sigma(S)=4.65, as a function
      of the large and small colloid particle densities. As in the case of the one
      component quasi-two-dimensional colloid system, the binary mixtures exhibit
      structural and dynamical heterogeneity. The distribution of large particle
      displacements over the time scale examined provides evidence for (at least) two
      different mechanisms of motion, one associated with particles in locally ordered
      regions and the other associated with particles in locally disordered regions.
      When rhoL*=Npisigma(L) (2)/4A< or =0.35, the addition of small colloid particles
      leads to a monotonic decrease in the large particle diffusion coefficient with
      increasing small particle volume fraction. When rhoL* > or =0.35 the addition of
      small colloid particles to a dense system of large colloid particles at first
      leads to an increase in the large particle diffusion coefficient, which is then
      followed by the expected decrease of the large particle diffusion coefficient
      with increasing small colloid particle volume fraction. The mode coupling theory
      of the ideal glass transition in three-dimensional systems makes a qualitative
      prediction that agrees with the initial increase in the large particle diffusion
      coefficient with increasing small particle density. Nevertheless, because the
      structural and dynamical heterogeneities of the quasi-two-dimensional colloid
      liquid occur within the field of equilibrium states, and the fluctuations
      generate locally ordered domains rather than just disordered regions of higher
      and lower density, it is suggested that mode coupling theory does not account for
      all classes of relevant fluctuations in a quasi-two-dimensional liquid.

PMID- 15511190
TI  - Dynamics of polymer packaging.
AB  - We use the stochastic rotation dynamics algorithm to investigate the packaging of
      flexible and semiflexible polymers into a capsid that is permeable to solvent
      molecules. The model takes into account hydrodynamic interactions arising due to
      local flow. The flexible chain maintains a random configuration as it is being
      fed into the capsid, in contrast to the semiflexible chain, whose configuration
      is initially spool-like, becoming more random at high packing. We measure the
      packing rate, which is found to decrease with the percentage of the chain packed
      and highlight the difference between the flexible and semiflexible chains.
      Reflecting experiments, we find pauses in the packing process for individual
      chains as the motor loses grip of the fluctuating beads. We also find that
      hydrodynamics is important, in that the packaging rate is faster when flow is
      included.

PMID- 15511191
TI  - Effect of confinement on coil-globule transition.
AB  - The equilibrium thermodynamic properties of a linear polymer chain confined to a
      space between two impenetrable walls (lines) at a distance D under various
      solvent conditions have been studied using series analysis and exact enumeration
      technique. We have calculated the end-to-end distance of polymer chain, which
      shows a nonmonotonic behavior with inter wall separation D. The density
      distribution profile shows a maxima at a particular value of (D=)D*. Around this
      D*, our results show that the collapse transition occurs at higher temperature as
      compared to its bulk value of 2d and 3d. The variation of theta-temperature with
      D shows a re-entrance behavior. We also calculate the force of compression
      exerted by the walls (lines) on the polymer.

PMID- 15511192
TI  - Molecular origin of demixing, prior to crystallization, of atactic
      polypropylene/isotactic polypropylene blends upon cooling from the melt.
AB  - An amorphous 50/50 atactic polypropylene (aPP)/isotactic polypropylene (iPP)
      mixture at 125 degrees C was simulated using a second nearest neighbor diamond
      lattice and a three states rotational isometric state model. The result suggests
      that at the liquidlike density that corresponds to the atmospheric pressure, aPP
      prefers to interact with other aPP chains rather than with iPP chains. The result
      is consistent with the inference of Keith and Padden [J. Appl. Phys. 35, 1286
      (1964)] that aPP and iPP will tend to separate from one another in their melt at
      125 degrees C, before the onset of crystallization of iPP. The tendency for
      immiscibility of the amorphous aPP/iPP blend is likely attributed to the presence
      of short syndiotactic sequences in the aPP chains adopting all-trans
      conformations. The attractive intermolecular interaction of pairs of such
      subchains at 125 degrees C promotes the separation of aPP from iPP. This
      interaction is weakened at higher temperature, where aPP and iPP become miscible.
      The result also shows that miscibility of the blend increases with increasing
      pressure. However, the origin of the pressure effect is not clear.

PMID- 15511193
TI  - Effect of branching and confinement on star-branched polymeric systems.
AB  - The effect of confinement, number of branches (functionality), and size of the
      molecules on various properties as a function of temperature of star-branched
      polymers confined between two walls was studied using Monte Carlo simulations
      with the parallel tempering technique. The coil-to-globule transition and the
      liquidlike to solidlike transition, similar to those observed for linear chains,
      were characterized in all systems by changes in the heat capacity, internal
      energy, and radius of gyration. The transitions were also characterized by the
      most probable isomeric structure at a given temperature. The radius of gyration
      of the star polymers was smaller than the values of linear chains when the number
      of arms f increased. For star chains with more than f=5 arms the values of the
      radius of gyration, and therefore the size of the molecules, were similar for
      every condition of confinement studied, especially at higher temperatures. As
      confinement was increased, the difference in the radius of gyration of linear
      chains and star polymers became even larger. The coil-to-globule transition
      temperatures shifted to higher temperatures as the size of the chains and the
      number of arms in a molecule were increased. Effects of confinement were higher
      on the properties of the system at the smallest separations (less than twice the
      monomer diameter), where the coil-to-globule transition shifted to lower
      temperatures. The liquidlike to solidlike transition was present at almost the
      same temperature for different conditions of confinement, chain size, and number
      of arms. The behavior of the systems for separations between the walls greater
      than five bead diameters was similar to the behavior in the unconfined case.
      Hence, no considerable effect of confinement was found above this separation.

PMID- 15511194
TI  - On the behavior of the volume viscosity of atom-molecule mixtures.

PMID- 15511195
TI  - [Giant cell arteritis].

PMID- 15511197
TI  - [Prevalence of atrial fibrillation and relationed factors in a population in the
      centre Madrid].
AB  - INTRODUCTION: Atrial fibrillation is the most common arrhythmia on clinical
      practice and an important risk factor for ictus. The aim of this study was to
      know the prevalence of this arrythmia in a central district of Madrid. MATERIAL
      AND METHODS: A retrospective study was done analysing medical records of 13,945
      patients belonging to a primary care centre of Madrid. Time of study: recruitment
      of data from September 2000 to May 2001; analysis of data: from September 2001 to
      May 2002. RESULTS: We obtained a total of 425 atrial fibrillations, 348 non
      valvular and 77 valvular. Global prevalence of atrial fibrillation in patients
      over 40 years in our area was 2.52%. (2.47% male, 2.55% female). Risk factors for
      atrial fibrillation more frequently found in non-valvular were high blood
      pressure (HBP), diabetes, ischaemic heart disease and left ventricular
      dysfunction. Among valvulars we found HBP, left atrial size over 45 mm and left
      ventricular dysfunction. CONCLUSIONS: Atrial fibrillation shows a prevalence and
      distribution in the studied area similar to that found in other European
      countries.

PMID- 15511196
TI  - [Analysis of a series of 55 patients with biopsy proven giant cell temporal
      arteritis].
AB  - INTRODUCTION: Our main aim with this study is to establish the epidemiologic and
      clinical features, treatment response and complications of a group composed of 55
      patients with biopsy proven temporal arteritis in a local hospital. MATERIAL AND
      METHODS: Retrospective study based on clinical records revision of patients
      diagnosed of giant cell arteritis (GCA) made by temporal artery biopsy between
      1989 and 2001. RESULTS: The approximated annual incidence of GCA in our area is
      4.1 cases per 100,000 persons over the age of 50. The mean age at diagnostic was
      74 years and the 78,2% were women. The most common symptom at diagnostic was
      headache (81.5%) followed by systemic manifestations (74.1%) and later we found
      jaw claudication (32,7%), visual impairment (30.2%), isquemic manifestations
      (17%). Polymyalgia rheumatica was associated to GCA in 49.1% of cases. The
      temporal artery explorations was abnormal in the 76.9% of patients. The mean
      initial dose of corticoids was 69 mg prednisone per day, with a half dose
      reduction time of .5 months. In spite of that, 24,1% of patients relapsed during
      the first year. The 38% of patients did some complications during the
      corticosteroid treatment. The ESR was lower 50 mm in 12.7% of patients; it was
      anaemia in the 37.7% and thrombocytosis in 32,1%. In these last patients we
      detected a relation between thrombocytosis and specific visual impairment.
      CONCLUSIONS: The incidence of GCA in our area is low. The results of our series
      aren't different from others publicated before in clinical manifestations, there
      is a prevalence of female sex and there is a relation between specific visual
      impairment and the presence of thrombocytosis.

PMID- 15511198
TI  - [Antimicrobial susceptibility of the bloodstream infections: a study in a
      nonteaching hospital].
AB  - BACKGROUND: To try established antimicrobial susceptibility patterns and
      frequency of both nosocomial and community-acquired bloodstream infections and
      and to try identified the prognostic factors that can be modified. MATERIAL AND
      METHODS: A prospective study of 310 bloodstream infections with clinical
      significance detected in a non teaching hospital over period from October 2000
      2001. A blood culture were identified by Bact-Alert system and the confirmation
      was performed by MicroScan system; an antimicrobial susceptibility test was
      performed by reference microdilution methods as described by NCCLS. We studied
      sentinel antimicrobial/organism combinations with potential clinical importance.
      Data were computerized using SPSS. Qualitative variables were compared using the
      X2 test or the Fisher exact test, and quantitative variables with t Student or
      ANOVA. RESULTS: Gram positive and Candida were frequently recovered in nosocomial
      bloodstreams. The proportion of oxacillin-resistant S. aureus isolates was 24%
      and the penicillin resistant pneumococci was 14%. Vancomycin was universal active
      against gram positive. Gram negatives were often recovered in community
      bloodstream. The proportion of EBSL E. coli isolates was < 2% and the proportion
      of multiresistance Pseudomonas aeruginosa was higher among UCI isolates. An
      independent risk factors for death identified after multivariate analysis was the
      inappropriate antimicrobial therapy OR 2.6. CONCLUSIONS: Ongoing surveillance of
      microbial pathogens and their resistance profiles is essential on local scale and
      permit the selection of appropriate antibiotic therapy which would be reduce the
      mortality.

PMID- 15511199
TI  - [Controversies about the clinical management of Whipple's disease].
AB  - BACKGROUND: There are a lot of controversies related to the diagnostic and
      therapeutic management of Whipple s disease. PATIENTS: We present 4 cases of
      Whipple's disease, collected from the Gastroenterology Service of the Hospital
      Ramon y Cajal, from Madrid. RESULTS: The average age was 69. The first symptoms
      were in order of frequency, arthralgias, loss of weight, arthritis, diarrhoea,
      fever, epigastric pain and neurologic symptoms. Three were treated with
      trimethoprim-sulphamethoxazol and one with cefixime. There were no recurrences.
      CONCLUSIONS: The endoscopic appearance of the duodenum is fundamental for the
      suspicion of the disease. The initial parenteral treatment may consist of
      ceftriaxone and try to avoid using streptomycine because of its toxicity,
      followed by oral trimethoprim-sulphamethoxazol. As an alternative to the latter,
      cefixime is usually effective. The typical findings of the duodenum biopsy can
      persist several months or years after finishing the treatment, decreasing the
      value of endoscopic pursuit after treatment.

PMID- 15511200
TI  - [Imaging advances in the diagnosis of neuroendocrine tumors].
AB  - We present two cases of neuroendocrine tumors: insulinoma and glucagonoma.
      Several diagnostic procedures are analysed including those useful to localize the
      tumor and its possible metastasis, as ultrasound, computed tomography, magnetic
      resonance imaging, angiography, endoscopic ultrasonography and somatostatin
      receptor scintigraphy. We suggest that the work up should begin with lesser
      invasive procedures such as CT and In111-labelled pentetreotide scan.

PMID- 15511202
TI  - [Peripartum cardiomyopathy with biventricular thrombi].
AB  - Peripartum cardiomyopathy is a rare cause of congestive heart failure which
      develops in the last month of pregnancy or during five months postpartum in women
      without previously known cardiac disease. Intraventricular thrombi are no unusual
      and can be identified by echocardiography. We report the case of a woman with
      peripartum cardiomyopathy whose echocardiographic study showed the presence of
      biventricular thrombi. This is a quite rare finding with only two cases reported
      in the literature. Diagnosis, treatment and special situations that could
      predispose to intracardiac thrombi formation are discussed.

PMID- 15511201
TI  - [Nonbacterial thrombotic endocarditis as initial event of lung cancer].
AB  - Nonbacterial thrombotic endocarditis (NBTE) is a rare cause of peripheral
      embolism. NBTE is usually associated with malignant diseases and
      hypercoagulability states. Echocardiography is a very useful technique for the
      diagnosis. However valvular lesions in NBTE are similar to valvular vegetations
      observed from infectious endocarditis (IE), so it s necessary to establish a
      differential diagnosis. The treatment of thrombotic endocarditis is
      controversial, but the literature coincides in the use of intravenous heparin. We
      describe the case of a 42 years old woman with stroke in which transesophageal
      echocardiography (TEE) was useful in establishing the diagnosis of NBTE. The
      infectious origin was excluded with the realization of a exhaustive microbiologic
      study. In the search of causes for NBTE a lung adenocarcinoma was detected. In
      the present case the diagnosis of endocarditis preceded the neoplastic disease
      diagnosis.

PMID- 15511203
TI  - [Neoplasms of unknown primary site].
AB  - Neoplasms of unknown primary site are tumor diseases, which are diagnosed by the
      pathologic studies of one of their metastases. The treatment of neoplasms of
      unknown primary site is not totally established, except in a few situations with
      specific therapeutical implications, and a better prognosis. The usual treatment
      of neoplasms of unknown primary site is the empirical chemotherapy with taxanes
      (paclitaxel or docetaxel) and platines (cisplatin or carboplatin)-based regimens,
      with different results in the trials.

PMID- 15511204
TI  - [A 41 year-old female with abdominal pain and fever of 24 hours].
AB  - A 41 year-old female with intrauterine contraceptive device (ICD) from 8 year ago
      that complained fever and abdominal pain during 24 hours and leucocytosis. The
      radiology examination tests showed cegal, appendiceal, and right ovary
      enlargement with swollen of fat adjacent. In the differential diagnosis should be
      include: appendicitis, diverticulitis, chronic inflammatory digestive disease or
      mesenterical adenitis. In the differential diagnosis included: ovarian neoplasm,
      endometriosis, ectopic pregnancy, ovarian torsion and pelvic inflammatory
      diseases. From pelvic infections, it is import consider pelvic inflammatory
      disease, genital tuberculosis and pelvic actinomycosis. With the antecedent of
      ICD, the clinic and the radiological finding as abdominal mass with invasion of
      adjacent structures and absence of adenopathy; the first diagnosis is a
      abdominopelvic actinomycosis and the second is a genital tuberculosis.

PMID- 15511205
TI  - [Pulmonary consolidation in adult after visiting the odontologist].

PMID- 15511206
TI  - [Pulmonary disease caused by Mycobacterium scrofulaceum].

PMID- 15511207
TI  - [Hyperaldosteronism and hyperparathyroidism: causality or coincidence?].

PMID- 15511208
TI  - [Septic arthritis caused by Neisseria meningitidis].

PMID- 15511209
TI  - [Aneurysm of the left pulmonary artery].

PMID- 15511210
TI  - [Inappropriate secretion of antidiuretic hormone secondary to paroxetine].

PMID- 15511211
TI  - [Apnea syndrome: risk factors for pseudotumor cerebri].

PMID- 15511212
TI  - Modulation of c-Kit/SCF pathway leads to alterations in topoisomerase-I activity
      in small cell lung cancer.
AB  - Small cell lung cancer (SCLC) is an aggressive type of lung cancer, for which
      cytotoxic chemotherapy appears to have reached its maximal efficacy. This
      neoplasm is characterized by the overexpression of several receptor tyrosine
      kinases (RTKs), especially c-Kit. The ligand for c-Kit is stem cell factor (SCF).
      In SCLC, SCF can influence c-Kit activation by autocrine or paracrine mechanisms.
      We have recently shown that the c-Kit/SCF pathway is operational in SCLC and can
      be inhibited by Glivec (STI571). Because the inhibition of topoisomerase-I (topo
      I) is one approach used to treat SCLC, we determined the effects of c-Kit/SCF
      signaling on topo-I activity. A unique phosphorylation of c-Kit on amino acid 823
      and amino acid 703 was identified with the SCF stimulation of H526 cells. We
      demonstrate that with SCF stimulation over 16 hours (dose response 0-100 ng/mL)
      in H526 SCLC cells (c-Kit positive, SCF responsive), a decrease in topo-I
      activity was observed, whereas in H82 SCLC cells (c-Kit negative, SCF
      unresponsive) there was no modulation of topo-I activity by SCF. Using STI571 (5
      microM, 16 hours) to inhibit the c-Kit pathway following stimulation with SCF
      (100 ng/mL), an upregulation of topo-I activity was observed in H526 cells but
      not in H82 cells. Performing viability assays, we show that STI571 in combination
      with topo-I inhibition by camptothecin or SN38, the active metabolite of
      irinotecan, can cooperatively inhibit H526 cell viability (but not H82 cell
      viability) for 72 hours. We also show that STI571 does not directly inhibit topo
      I activity in SCLC. The combination of STI571 with topo-I inhibition could
      provide a useful combination in the treatment of SCLC.

PMID- 15511213
TI  - Effect of platelet-derived growth factor on the development and persistence of
      asbestos-induced fibroproliferative lung disease.
AB  - Platelet-derived growth factor (PDGF) isoforms and PDGF receptor-alpha are
      upregulated in fibroproliferative lesions in response to asbestos exposure. To
      examine the functional role of PDGF in asbestos-induced lung disease, we have
      evaluated the impact of PDGF-B overexpression in the lung on the development of
      pulmonary fibrosis induced by asbestos inhalation. Transgenic mice expressing
      PDGF-B from the surfactant protein C promoter and wild-type C57BL/6 mice were
      exposed to aerosolized chrysotile asbestos fibers via three different exposure
      regimens: 3 consecutive days to 9 mg/m(3), once a week for 5 weeks to 12 mg/m(3),
      or once a week for 8 weeks to 11 mg/m(3). The 3-day exposure did not produce
      fibroproliferative lesions in SPC-PDGFB or wild-type mice, indicating that PDGF
      expression did not increase susceptibility to a subthreshold dose of asbestos.
      Transgenic and wild-type mice subjected to the 5-week exposure protocol exhibited
      similar fibrogenic lesions histologically 48 hours and 8 weeks postexposure, but
      lungs from transgenic mice had elevated lung hydroxyproline content 8 weeks
      postexposure relative to wild-type mice. In addition, SPC-PDGFB transgenic mice
      developed pronounced thickening of arterioles following the 5-week exposure
      regimen. Mice exposed to asbestos for 8 weeks and examined 10 months later showed
      pronounced, diffuse fibrotic lesions of terminal bronchioles and alveolar ducts,
      but no histological differences between transgenic and nontransgenic mice were
      observed. These results indicated that PDGF-B overexpression can stimulate
      increased collagen deposition and vascular smooth muscle hyperplasia following
      asbestos inhalation and that a limited exposure (8 times) to chrysotile aerosol
      can produce long-lasting fibrotic lesions. The 8-week exposure regimen provides
      an animal model that encompasses an important aspect of human asbestosis-i.e.,
      persistence of fibrosis for long periods after cessation of asbestos exposure.

PMID- 15511214
TI  - Comparison of genotoxicity of textile dyestuffs in Salmonella mutagenicity assay,
      in vitro micronucleus assay, and single cell gel/comet assay.
AB  - The mutagenicity of textile dyes is an important consideration for the assurance
      of consumer protection and work safety. The mutagenicity testing of textile
      dyestuffs is crucial for accurately predicting health risks for consumers and
      workers exposed to dyes. Unfortunately, these data are often lacking. We studied
      the genotoxic activity of ten selected commercial textile dyestuffs, which are
      made up of mixtures of azo dyes and azo metal complex dyes as well as two
      anthraquinone dyestuffs. We used the Salmonella mutagenicity assay and cultured
      human keratinocytes (HaCaT cell line). In the S. typhimurium strain TA98, with
      and without S9, eight often dyestuffs investigated, and in strain TA 100, with
      and without S9, six often dyes caused frameshift mutations and base-pair
      substitutions in the dose range of 1-5000 microg/plate in a dose-related manner.
      All dyes, including those negative in the Salmonella mutagenicity assay, induced
      clastogenic effects in the in vitro micronucleus (MN) test in HaCaT cells as
      direct-acting mutagens in the concentration range of 5-150 microg/mL and with
      maximum MN frequencies between 1.1 and 7.2%, compared to negative controls that
      showed 0.2-0.4% MN cells. In the single cell gel/comet assay, all ten dyestuffs
      investigated caused DNA damage in HaCaT keratinocytes. The alkaline (pH >13)
      version used is capable of detecting DNA single strand breaks, alkali-labile
      sites, and DNA-DNA/DNA-protein cross-linking. Under the conditions of these
      screening tests, the textile dyes investigated are direct-acting genotoxic
      substances. The HaCaT cells testing protocol proposed has been shown to be an
      appropriate test system for evaluating mutagenicity of textile dyes on a base
      level.

PMID- 15511215
TI  - Genotoxicity of degradation products of textile dyes evaluated with rec-assay
      after PhotoFenton and ligninase treatment.
AB  - Fourteen textile and biological dyes, belonging to the azo, triphenylmethane,
      anthraquinone, heterocyclic, oxazine, and methine/polymethine groups, were
      degraded using the PhotoFenton treatment (PFT) and the Phanerochaete
      chrysosporium crude ligninase enzyme (ED) treatment. The genotoxicity of the dyes
      and of their degradation products were assessed with the rec-assay. We found that
      the genotoxicity depended on the dye and on the method of degradation. In
      general, PFT was better than ED in decreasing the genotoxicity. Basic dyes showed
      complete or maximum loss of genotoxicity, whereas the vat group was more
      resistant. The azo group showed varied results. Crystal Violet was the only dye
      whose genotoxicity increased after PFT. Our results suggest that PFT and ED are
      two effective treatment methods to reduce the genotoxicity of dyes in waste
      waters.

PMID- 15511216
TI  - Protective effect of diphenylmethyl selenocyanate against carbon tetrachloride
      induced hepatotoxicity in vivo.
AB  - Carbon tetrachloride (CCl(4)) is a known hepatotoxic compound working through the
      generation of reactive free radicals. Selenium (Se) is an essential trace element
      required by animals and humans for protection against xenobiotic compounds. In
      this study, Se, as diphenylmethyl selenocyanate, has been evaluated for its
      protective action against CCl(4)-induced hepatotoxicity in Swiss albino mice.
      Treatment with Se compound was found to upregulate different phase II detoxifying
      enzymes (catalase, superoxide dismutases, reduced glutathione, and glutathione
      transferase) in liver of mice challenged with different doses of CCl(4) as
      compared to the CCl(4) control, when measured after 24 hours of CCl(4) treatment
      (p < 0.01). The Se compound also significantly (p < 0.01) inhibited the level of
      membrane lipid peroxidation and serum transferase activity (ALT and AST) in the
      treated group as compared to the control group.

PMID- 15511217
TI  - Mutagenic potential of Mancozeb in Salmonella typhimurium.
AB  - Mancozeb, a dithiocarbamate fungicide, was examined for its possible mutagenic
      activity using Salmonella typhimurium tester strains TA97a, TA98, TA100, and
      TA102. We found that Mancozeb exhibited toxic effects at the dose of 40
      microg/plate and higher with all tester strains. Mancozeb showed dose-dependent
      increases in the number of revertants with and without metabolic activation when
      it was dissolved in DMSO or acetone with strain TA97a; however, the number of
      revertants at the highest dose was less than two-fold compared to control values.
      We postulate that the true mutagenic potential of Mancozeb may be masked by its
      toxic effect to the tester strain used.

PMID- 15511218
TI  - Urinary excretion of nickel after dermal application of Nigerian light crude oil.
AB  - We examined the pattern of excretion of crude oil nickel (CON) in urine and
      feces. Adult male guinea pigs were treated with a single dose of 5 mL/kg b.w.
      Nigerian Bonny light crude oil applied on the skin. Untreated guinea pigs served
      as controls. The CON content was measured spectrophotometrically by the
      dimethylglyoxime reaction following nitric acid:perchloric acid: sulfuric acid
      (3:1:1) digestion of blood, urine, and feces samples at 2, 4, 8, and 16 days
      after the crude oil application. We found a peak of CON excretion in the urine at
      2 days and a return to the control level at 16 days. There was no change in the
      CON content in the feces during the observation time. We found a peak of CON
      content in the blood at 8 days and a return to control values at 16 days. The
      implication of these excretion and transport patterns of CON is discussed vis-a
      vis the potential application of the urinary nickel content as a valid
      biochemical indicator of human exposure to environmentally spilled crude oil.

PMID- 15511219
TI  - Human CHMP6, a myristoylated ESCRT-III protein, interacts directly with an ESCRT
      II component EAP20 and regulates endosomal cargo sorting.
AB  - CHMP6 (charged multivesicular body protein 6) is a human orthologue of yeast Vps
      (vacuolar protein sorting) 20, a component of ESCRT (endosomal sorting complex
      required for transport)-III. Various CHMP6 orthologues in organisms ranging from
      yeast to humans contain the N-myristoylation consensus sequence at each N
      terminus. Metabolic labelling of HEK-293 (human embryonic kidney) cells showed
      the incorporation of [3H]myristate into CHMP6 fused C-terminally to GFP (green
      fluorescent protein) (CHMP6-GFP). Interactions of CHMP6 with another ESCRT-III
      component CHMP4b/Shax [Snf7 (sucrose non-fermenting 7) homologue associated with
      Alix] 1, one of three paralogues of human Vps32/Snf7, and with EAP20 (ELL
      associated protein 20), a human counterpart of yeast Vps25 and component of ESCRT
      II, were observed by co-immunoprecipitation of epitope-tagged proteins expressed
      in HEK-293 cells. The in vitro pull-down assays using their recombinant proteins
      purified from Escherichia coli demonstrated direct physical interactions which
      were mediated by the N-terminal basic half of CHMP6. Overexpressed CHMP6-GFP in
      HeLa cells exhibited a punctate distribution throughout the cytoplasm especially
      in the perinuclear area, as revealed by fluorescence microscopic analysis.
      Accumulation of LBPA (lysobisphosphatidic acid), a major phospholipid in internal
      vesicles of an MVB (multivesicular body), was observed in the CHMP6-GFP
      localizing area. FLAG-tagged EAP20 distributed diffusely, but exhibited a
      punctate distribution on co-expression with CHMP6-GFP. Overexpression of CHMP6
      GFP caused reduction of transferrin receptors on the plasma membrane surface, but
      caused their accumulation in the cytoplasm. Ubiquitinated proteins and
      endocytosed EGF continuously accumulated in CHMP6-GFP-expressing cells. These
      results suggest that CHMP6 acts as an acceptor for ESCRT-II on endosomal
      membranes and regulates cargo sorting.

PMID- 15511220
TI  - The recombinant dihydropyridine receptor II-III loop and partly structured 'C'
      region peptides modify cardiac ryanodine receptor activity.
AB  - A physical association between the II-III loop of the DHPR (dihydropryidine
      receptor) and the RyR (ryanodine receptor) is essential for excitation
      contraction coupling in skeletal, but not cardiac, muscle. However, peptides
      corresponding to a part of the II-III loop interact with the cardiac RyR2
      suggesting the possibility of a physical coupling between the proteins. Whether
      the full II-III loop and its functionally important 'C' region (cardiac DHPR
      residues 855-891 or skeletal 724-760) interact with cardiac RyR2 is not known and
      is examined in the present study. Both the cardiac DHPR II-III loop (CDCL) and
      cardiac peptide (C(c)) activated RyR2 channels at concentrations >10 nM. The
      skeletal DHPR II-III loop (SDCL) activated channels at < or =100 nM and weakly
      inhibited at > or =1 microM. In contrast, skeletal peptide (C(s)) inhibited
      channels at all concentrations when added alone, or was ineffective if added in
      the presence of C(c). Ca2+-induced Ca2+ release from cardiac sarcoplasmic
      reticulum was enhanced by CDCL, SDCL and the C peptides. The results indicate
      that the interaction between the II-III loop and RyR2 depends critically on the
      'A' region (skeletal DHPR residues 671-690 or cardiac 793-812) and also involves
      the C region. Structure analysis indicated that (i) both C(s) and C(c) are random
      coil at room temperature, but, at 5 degrees C, have partial helical regions in
      their N-terminal and central parts, and (ii) secondary-structure profiles for
      CDCL and SDCL are similar. The data provide novel evidence that the DHPR II-III
      loop and its C region interact with cardiac RyR2, and that the ability to
      interact is not isoform-specific.

PMID- 15511221
TI  - G protein-coupled receptor 30 down-regulates cofactor expression and interferes
      with the transcriptional activity of glucocorticoid.
AB  - G protein-coupled receptor 30 (GPR30) has previously been described to be
      important in steroid-mediated growth and to inhibit cell proliferation. Here we
      investigated whether the effect of GPR30 on cell growth is dependent on steroid
      hormone receptors. We stably introduced GPR30 in immortalized normal mammary
      epithelial (HME) cells using retroviruses for gene delivery. GPR30 inhibited the
      growth and proliferation of the cells. They expressed glucocorticoid receptor,
      but not estrogen or progesterone receptor. GPR30 down-regulated the expression of
      cofactor transcription intermediary factor 2 (TIF2) analyzed using quantitative
      RT-PCR analysis, and also diminished the expression of TIF2 at protein level
      analyzed by Western blotting using nuclear extracts from mammary epithelial
      cells. When HME cells were transiently transfected with the glucocorticoid
      response element MMTV-luc reporter plasmid, stable expression of GPR30 resulted
      in the abolition of ligand-induced transactivation of the promoter. In COS cells,
      transient transfection of GPR30 with glucocorticoid receptor alpha resulted in an
      abrogation of the MMTV-luc and GRE-luc reporter activities induced by
      dexamethasone. The results suggest a novel mechanism by which membrane-initiated
      signaling interferes with steroid signaling.

PMID- 15511222
TI  - Investigation of the substrate specificity of a beta-glycosidase from Spodoptera
      frugiperda using site-directed mutagenesis and bioenergetics analysis.
AB  - The specificity of the Spodoptera frugiperda digestive beta-glycosidase
      (Sfbetagly50) for fucosides, glucosides and galactosides is determined by
      noncovalent interactions of glycone 6-OH and glycone 4-OH with the active-site
      residues Q39 and E451. Site-directed mutagenesis and enzyme steady-state kinetics
      were described, showing that replacement of E451 with glutamine increased the
      preference of Sfbetagly50 for glucosides in comparison to galactosides, whereas
      replacing E451 with serine had the opposite effect. In contrast, the replacement
      of E451 with aspartate did not change Sfbetagly50 specificity. The energy of the
      interactions formed by these different residues with the axial and equatorial
      glycone 4-OH were also measured, showing that the increase in preference for
      galactosides resulted from a larger energy decrease in the interaction with
      equatorial 4-OH than with axial 4-OH (22.6 vs. 13.9 kJ x mol(-1)), whereas the
      increase in preference for glucosides was caused by an energy reduction in the
      interaction with the axial 4-OH (5.1 kJ x mol(-1)). The introduction of glutamine
      at position 451 or of asparagine at position 39 increased the preference of
      Sfbetagly50 for fucosides in comparison to galactosides, whereas the presence of
      aspartate or serine at position 451 had less effect on this preference. The
      hydrolysis of fucosides was favored because glutamine at position 451 increased a
      steric hindrance with 6-OH of 7.1 kJ x mol(-1) and asparagine at position 39
      disrupted a favorable interaction with this same hydroxyl. In conclusion, it is
      proposed that the specificity of new beta-glycosidase mutants can be predicted by
      combining and adding energy of the enzyme-substrate interactions evaluated in the
      present study.

PMID- 15511224
TI  - Donor substrate regulation of transketolase.
AB  - The influence of substrates on the interaction of apotransketolase with thiamin
      diphosphate was investigated in the presence of magnesium ions. It was shown that
      the donor substrates, but not the acceptor substrates, enhance the affinity of
      the coenzyme either to only one active center of transketolase or to both active
      centers, but to different degrees in each, resulting in a negative cooperativity
      for coenzyme binding. In the absence of donor substrate, negative cooperativity
      is not observed. The donor substrate did not affect the interaction of the
      apoenzyme with the inactive coenzyme analogue, N3'-pyridyl-thiamin diphosphate.
      The influence of the donor substrate on the coenzyme-apotransketolase interaction
      was predicted as a result of formation of the transketolase reaction intermediate
      2-(alpha,beta-dihydroxyethyl)-thiamin diphosphate, which exhibited a higher
      affinity to the enzyme than thiamin diphosphate. The enhancement of thiamin
      diphosphate's affinity to apotransketolase in the presence of donor substrate is
      probably one of the mechanisms underlying the substrate-affected transketolase
      regulation at low coenzyme concentrations.

PMID- 15511223
TI  - A novel pathway for sequential transformation of 7-dehydrocholesterol and
      expression of the P450scc system in mammalian skin.
AB  - Following up on our previous findings that the skin possesses steroidogenic
      activity from progesterone, we now show widespread cutaneous expression of the
      full cytochrome P450 side-chain cleavage (P450scc) system required for the
      intracellular catalytic production of pregnenolone, i.e. the genes and proteins
      for P450scc enzyme, adrenodoxin, adrenodoxin reductase and MLN64. Functionality
      of the system was confirmed in mitochondria from skin cells. Moreover, purified
      mammalian P450scc enzyme and, most importantly, mitochondria isolated from
      placenta and adrenals produced robust transformation of 7-dehydrocholesterol (7
      DHC; precursor to cholesterol and vitamin D3) to 7-dehydropregnenolone (7-DHP).
      Product identity was confirmed by comparison with the chemically synthesized
      standard and chromatographic, MS and NMR analyses. Reaction kinetics for the
      conversion of 7-DHC into 7-DHP were similar to those for cholesterol conversion
      into pregnenolone. Thus, 7-DHC can form 7-DHP through P450scc side-chain
      cleavage, which may serve as a substrate for further conversions into hydroxy
      derivatives through existing steroidogenic enzymes. In the skin, 5,7-steroidal
      dienes (7-DHP and its hydroxy derivatives), whether synthesized locally or
      delivered by the circulation, may undergo UVB-induced intramolecular
      rearrangements to vitamin D3-like derivatives. This novel pathway has the
      potential to generate a variety of molecules depending on local steroidogenic
      activity and access to UVB.

PMID- 15511225
TI  - Mimicking phosphorylation of the small heat-shock protein alphaB-crystallin
      recruits the F-box protein FBX4 to nuclear SC35 speckles.
AB  - The mammalian small heat shock protein alphaB-crystallin can be phosphorylated at
      three different sites, Ser19, Ser45 and Ser59. We compared the intracellular
      distribution of wild-type, nonphosphorylatable and all possible
      pseudophosphorylation mutants of alphaB-crystallin by immunoblot and
      immunocytochemical analyses of stable and transiently transfected cells. We
      observed that pseudophosphorylation at two (especially S19D/S45D) or all three
      (S19D/S45D/S59D) sites induced the partial translocation of alphaB-crystallin
      from the detergent-soluble to the detergent-insoluble fraction. Double
      immunofluorescence studies showed that the pseudophosphorylation mutants
      localized in nuclear speckles containing the splicing factor SC35. The alphaB
      crystallin mutants in these speckles were resistant to mild detergent treatment,
      and also to DNase I or RNase A digestion, indicating a stable interaction with
      one or more speckle proteins, not dependent on intact DNA or RNA. We further
      found that FBX4, an adaptor protein of the ubiquitin-protein isopeptide ligase
      SKP1/CUL1/F-box known to interact with pseudophosphorylated alphaB-crystallin,
      was also recruited to SC35 speckles when cotransfected with the
      pseudophosphorylation mutants. Because SC35 speckles also react with an antibody
      against alphaB-crystallin endogenously phosphorylated at Ser45, our findings
      suggest that alphaB-crystallin has a phosphorylation-dependent role in the
      ubiquitination of a component of SC35 speckles.

PMID- 15511226
TI  - Alternative substrates for wild-type and L109A E. coli CTP synthases: kinetic
      evidence for a constricted ammonia tunnel.
AB  - Cytidine 5'-triphosphate (CTP) synthase catalyses the ATP-dependent formation of
      CTP from uridine 5'-triphosphate using either NH(3) or l-glutamine as the
      nitrogen source. The hydrolysis of glutamine is catalysed in the C-terminal
      glutamine amide transfer domain and the nascent NH(3) that is generated is
      transferred via an NH(3) tunnel [Endrizzi, J.A., Kim, H., Anderson, P.M. &
      Baldwin, E.P. (2004) Biochemistry43, 6447-6463] to the active site of the N
      terminal synthase domain where the amination reaction occurs. Replacement of
      Leu109 by alanine in Escherichia coli CTP synthase causes an uncoupling of
      glutamine hydrolysis and glutamine-dependent CTP formation [Iyengar, A. & Bearne,
      S.L. (2003) Biochem. J.369, 497-507]. To test our hypothesis that L109A CTP
      synthase has a constricted or a leaky NH(3) tunnel, we examined the ability of
      wild-type and L109A CTP synthases to utilize NH(3), NH(2)OH, and NH(2)NH(2) as
      exogenous substrates, and as nascent substrates generated via the hydrolysis of
      glutamine, gamma-glutamyl hydroxamate, and gamma-glutamyl hydrazide,
      respectively. We show that the uncoupling of the hydrolysis of gamma-glutamyl
      hydroxamate and nascent NH(2)OH production from N(4)-hydroxy-CTP formation is
      more pronounced with the L109A enzyme, relative to the wild-type CTP synthase.
      These results suggest that the NH(3) tunnel of L109A, in the presence of bound
      allosteric effector guanosine 5'-triphosphate, is not leaky but contains a
      constriction that discriminates between NH(3) and NH(2)OH on the basis of size.

PMID- 15511227
TI  - Solution structure of Cu6 metallothionein from the fungus Neurospora crassa.
AB  - The 3D-solution structure of Neurospora crassa Cu(6)-metallothionein (NcMT)
      polypeptide backbone was determined using homonuclear, multidimensional (1)H-NMR
      spectroscopy. It represents a new metallothionein (MT) fold with a protein chain
      where the N-terminal half is left-handed and the C-terminal half right-handedly
      folded around a copper(I)-sulfur cluster. As seen with other MTs, the protein
      lacks definable secondary structural elements; however, the polypeptide fold is
      unique. The metal coordination and the cysteine spacing defines this unique fold.
      NcMT is only the second MT in the copper-bound form to be structurally
      characterized and the first containing the -CxCxxxxxCxC- motif. This motif is
      found in a variety of mammalian MTs and metalloregulatory proteins. The in vitro
      formation of the Cu(6)NcMT identical to the native Cu(6)NcMT was dependent upon
      the prior formation of the Zn(3)NcMT and its titration with Cu(I). The enhanced
      sensitivity and resolution of the 800 MHz (1)H-NMR spectral data permitted the 3D
      structure determination of the polypeptide backbone without the substitution and
      utilization of the NMR active spin 1/2 metals such as (113)Cd and (109)Ag. These
      restraints have been necessary to establish specific metal to cysteine restraints
      in 3D structural studies on this family of proteins when using lower field, less
      sensitive (1)H-NMR spectral data. The accuracy of the structure calculated
      without these constraints is, however, supported by the similarities of the 800
      MHz structures of the alpha-domain of mouse MT1 compared to the one recalculated
      without metal-cysteine connectivities.

PMID- 15511228
TI  - IFN-gamma enhances TRAIL-induced apoptosis through IRF-1.
AB  - Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member
      of the TNF family and a potent inducer of apoptosis. TRAIL has been shown to
      effectively limit tumor growth in vivo without detectable cytotoxic side-effects.
      Interferon (IFN)-gamma often modulates the anticancer activities of TNF family
      members including TRAIL. However, little is known about the mechanism. To explore
      the mechanism, A549, HeLa, LNCaP, Hep3B and HepG2 cells were pretreated with IFN
      gamma, and then exposed to TRAIL. IFN-gamma pretreatment augmented TRAIL-induced
      apoptosis in all these cell lines. A549 cells were selected and further
      characterized for IFN-gamma action in TRAIL-induced apoptosis. Western blotting
      analyses revealed that IFN-gamma dramatically increased the protein levels of
      interferon regulatory factor (IRF)-1, but not TRAIL receptors (DR4 and DR5) and
      pro-apoptotic (FADD and Bax) and anti-apoptotic factors (Bcl-2, Bcl-XL, cIAP-1,
      cIAP-2 and XIAP). To elucidate the functional role of IRF-1 in IFN-gamma-enhanced
      TRAIL-induced apoptosis, IRF-1 was first overexpressed by using an adenoviral
      vector AdIRF-1. IRF-1 overexpression minimally increased apoptotic cell death,
      but significantly enhanced apoptotic cell death induced by TRAIL when infected
      cells were treated with TRAIL. In further experiments using an antisense
      oligonucleotide, a specific repression of IRF-1 expression abolished enhancer
      activity of IFN-gamma for TRAIL-induced apoptosis. Therefore, our data indicate
      that IFN-gamma enhances TRAIL-induced apoptosis through IRF-1.

PMID- 15511229
TI  - Folding of epidermal growth factor-like repeats from human tenascin studied
      through a sequence frame-shift approach.
AB  - In order to investigate the factors that determine the correct folding of
      epidermal growth factor-like (EGF) repeats within a multidomain protein, we
      prepared a series of six peptides that, taken together, span the sequence of two
      EGF repeats of human tenascin, a large protein from the extracellular matrix. The
      peptides were selected by sliding a window of the average length of tenascin EGF
      repeats over the sequence of EGF repeats 13 and 14. We thus obtained six
      peptides, EGF-f1 to EGF-f6, that are 33 residues long, contain six cysteines
      each, and bear a partial overlap in the sequence. While EGF-f1 corresponds to the
      native EGF-14 repeat, the others are frame-shifted EGF repeats. We carried out
      the oxidative folding of these peptides in vitro, analyzed the reaction mixtures
      by acid trapping followed by LC-MS, and isolated some of the resulting products.
      The oxidative folding of the native EGF-14 peptide is fast, produces a single
      three-disulfide species with an EGF-like disulfide topology and a marked
      difference in the RP-HPLC retention time compared with the starting product. On
      the contrary, frame-shifted peptides fold more slowly and give mixtures of three
      disulfide species displaying RP-HPLC retention times that are closer to those of
      the reduced peptides. In contrast to the native EGF-14, the three-disulfide
      products that could be isolated are mainly unstructured, as determined by CD and
      NMR spectroscopy. We conclude that both kinetics and thermodynamics drive the
      correct pairing of cysteines, and speculate about how cysteine mispairing could
      trigger disulfide reshuffling in vivo.

PMID- 15511230
TI  - The N-linked oligosaccharides of aminopeptidase N from Manduca sexta: site
      localization and identification of novel N-glycan structures.
AB  - Mass spectrometric studies on the N-linked glycans of aminopeptidase 1 from
      Manduca sexta have revealed unusual structures not previously observed on any
      insect glycoprotein. Structure elucidation of these oligosaccharides was carried
      out by high-energy collision-induced dissociation (CID) using a matrix-assisted
      laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF) tandem
      mass spectrometer. These key experiments revealed that three out of the four N
      linked glycosylation sites in this protein (Asn295, Asn623 and Asn752) are
      occupied with highly fucosylated N-glycans that possess unusual difucosylated
      cores. Cross-ring fragment ions and 'internal' fragment ions observed in the CID
      spectra, showed that these fucoses are found at the 3-position of proximal GlcNAc
      and at the 3-position of distal GlcNAc in the chitobiose unit. The latter
      substitution has only been previously observed in nematodes. In addition, these
      core structures can be decorated with novel fucosylated antennae composed of
      Fucalpha(1-3)GlcNAc. Key fragment ions revealed that these antennae are
      predominantly found on the upper 6-arm of the core mannose. The paucimannosidic N
      glycan (Man(3)GlcNAc(2)), commonly found on other insect glycoproteins, is the
      predominant oligosaccharide found at the remaining N-glycosylation site (Asn609).

PMID- 15511231
TI  - Trehalose synthase of Mycobacterium smegmatis: purification, cloning, expression,
      and properties of the enzyme.
AB  - Trehalose synthase (TreS) catalyzes the reversible interconversion of trehalose
      (glucosyl-alpha,alpha-1,1-glucose) and maltose (glucosyl-alpha1-4-glucose). TreS
      was purified from the cytosol of Mycobacterium smegmatis to give a single protein
      band on SDS gels with a molecular mass of approximately 68 kDa. However, active
      enzyme exhibited a molecular mass of approximately 390 kDa by gel filtration
      suggesting that TreS is a hexamer of six identical subunits. Based on amino acid
      compositions of several peptides, the treS gene was identified in the M.
      smegmatis genome sequence, and was cloned and expressed in active form in
      Escherichia coli. The recombinant protein was synthesized with a (His)(6) tag at
      the amino terminus. The interconversion of trehalose and maltose by the purified
      TreS was studied at various concentrations of maltose or trehalose. At a maltose
      concentration of 0.5 mm, an equilibrium mixture containing equal amounts of
      trehalose and maltose (42-45% of each) was reached during an incubation of about
      6 h, whereas at 2 mm maltose, it took about 22 h to reach the same equilibrium.
      However, when trehalose was the substrate at either 0.5 or 2 mm, only about 30%
      of the trehalose was converted to maltose in >or= 12 h, indicating that maltose
      is the preferred substrate. These incubations also produced up to 8-10% free
      glucose. The K(m) for maltose was approximately 10 mm, whereas for trehalose it
      was approximately 90 mm. While beta,beta-trehalose, isomaltose (alpha1,6-glucose
      disaccharide), kojibiose (alpha1,2) or cellobiose (beta1,4) were not substrates
      for TreS, nigerose (alpha1,3-glucose disaccharide) and alpha,beta-trehalose were
      utilized at 20 and 15%, respectively, as compared to maltose. The enzyme has a pH
      optimum of about 7 and is inhibited in a competitive manner by Tris buffer.
      [(3)H]Trehalose is converted to [(3)H]maltose even in the presence of a 100-fold
      or more excess of unlabeled maltose, and [(14)C]maltose produces [(14)C]trehalose
      in excess unlabeled trehalose, suggesting the possibility of separate binding
      sites for maltose and trehalose. The catalytic mechanism may involve scission of
      the incoming disaccharide and transfer of a glucose to an enzyme-bound glucose,
      as [(3)H]glucose incubated with TreS and either unlabeled maltose or trehalose
      results in formation of [(3)H]disaccharide. TreS also catalyzes production of a
      glucosamine disaccharide from maltose and glucosamine, suggesting that this
      enzyme may be valuable in carbohydrate synthetic chemistry.

PMID- 15511232
TI  - Allosteric water and phosphate effects in Hoplosternum littorale hemoglobins.
AB  - This paper reports the results obtained using the osmotic stress method applied
      to the purified cathodic and anodic hemoglobins (Hbs) from the catfish
      Hoplosternum littorale, a species that displays facultative accessorial air
      oxygenation. We demonstrate that water potential affects the oxygen affinity of
      H. littorale Hbs in the presence of an inert solute (sucrose). Oxygen affinity
      increases when water activity increases, indicating that water molecules
      stabilize the high-affinity state of the Hb. This effect is the same as that
      observed in tetrameric vertebrate Hbs. We show that both anodic and cathodic Hbs
      show conformational substrates similar to other vertebrate Hbs. For both Hbs,
      addition of anionic effectors, especially chloride, strongly increases the number
      of water molecules bound, although anodic Hb did not exhibit sensitivity to
      saturating levels of ATP. Accordingly, for both Hbs, we propose that the deoxy
      conformations coexist in at least two anion-dependent allosteric states, T(o) and
      T(x), as occurs for human Hb. We found a single phosphate binding site for the
      cathodic Hb.

PMID- 15511233
TI  - Reformable intramolecular cross-linking of the N-terminal domain of heparin
      cofactor II: effects on enzyme inhibition.
AB  - The crystal structure of a heparin cofactor II (HCII)-thrombin Michaelis complex
      has revealed extensive contacts encompassing the N-terminal domain of HCII and
      exosite I of the proteinase. In contrast, the location of the N-terminal
      extension in the uncomplexed inhibitor was unclear. Using a disulfide cross
      linking strategy, we demonstrate that at least three different sites (positions
      52, 54 and 68) within the N terminus may be tethered in a reformable manner to
      position 195 in the loop region between helix D and strand s2A of the HCII
      molecule, suggesting that the N-terminal domain may interact with the inhibitor
      scaffold in a permissive manner. Cross-linking of the N terminus to the HCII body
      does not strongly affect the inhibition of alpha-chymotrypsin, indicating that
      the reactive site loop sequences of the engineered inhibitor variants, required
      for interaction with one of the HCII target enzymes, are normally accessible. In
      contrast, intramolecular tethering of the N-terminal extension results in a
      drastic decrease of alpha-thrombin inhibitory activity, both in the presence and
      in the absence of glycosaminoglycans. Treatment with dithiothreitol and
      iodoacetamide restores activity towards alpha-thrombin, suggesting that release
      of the N terminus of HCII is an important component of the multistep interaction
      between the inhibitor and alpha-thrombin.

PMID- 15511234
TI  - Unfolding process of rusticyanin: evidence of protein aggregation.
AB  - The unfolding process of the Blue Copper Protein (BCP) rusticyanin (Rc) has been
      studied using a wide variety of biochemical techniques. Fluorescence and CD
      spectroscopies reveal that the copper ion plays an essential role in stabilizing
      the protein and that the oxidized form is more efficient than the reduced species
      in this respect. The addition of guanidinium chloride to Rc samples produces
      aggregation of the protein. Gel filtration chromatography and glutaraldehyde
      cross-linking experiments confirm the formation of such aggregates. Among the
      BCPs, this feature is exclusive to Rc. The aggregation could be related to the
      large molecular mass and large number of hydrophobic residues of this protein
      compared with those of other BCPs.

PMID- 15511235
TI  - Coexpression, purification and characterization of the E and S subunits of
      coenzyme B(12) and B(6) dependent Clostridium sticklandii D-ornithine aminomutase
      in Escherichia coli.
AB  - D-Ornithine aminomutase from Clostridium sticklandii comprises two strongly
      associating subunits, OraS and OraE, with molecular masses of 12,800 and 82,900
      Da. Previous studies have shown that in Escherichia coli the recombinant OraS
      protein is synthesized in the soluble form and OraE as inclusion bodies.
      Refolding experiments also indicate that the interactions between OraS and OraE
      and the binding of either pyridoxal phosphate (PLP) or adenosylcobalamin (AdoCbl)
      play important roles in the refolding process. In this study, the DNA fragment
      containing both genes was cloned into the same expression vector and coexpression
      of the oraE and oraS genes was carried out in E. coli. The solubility of the
      coexpressed OraS and OraE increases with decreasing isopropyl thio-beta-D
      galactoside induction temperature. Among substrate analogues tested, only 2,4
      diamino-n-butyric acid displays competitive inhibition of the enzyme with a K(i)
      of 96 +/- 14 microm. Lys629 is responsible for the binding of PLP. The apparent
      K(d) for coenzyme B(6) binding to d-ornithine aminomutase is 224 +/- 41 nm as
      measured by equilibrium dialysis. The mutant protein, OraSE-K629M, is
      successfully expressed. It is catalytically inactive and unable to bind PLP.
      Because no coenzyme is involved in protein folding during in vivo translation of
      OraSE-K629M in E. coli, in vitro refolding of the enzyme employs a different
      folding mechanism. In both cases, the association of the S and E subunit is
      important for D-ornithine aminomutase to maintain an active conformation.

PMID- 15511236
TI  - Antisense glutaminase inhibition decreases glutathione antioxidant capacity and
      increases apoptosis in Ehrlich ascitic tumour cells.
AB  - Glutamine is an essential amino acid in cancer cells and is required for the
      growth of many other cell types. Glutaminase activity is positively correlated
      with malignancy in tumours and with growth rate in normal cells. In the present
      work, Ehrlich ascites tumour cells, and their derivative, 0.28AS-2 cells,
      expressing antisense glutaminase mRNA, were assayed for apoptosis induced by
      methotrexate and hydrogen peroxide. It is shown that Ehrlich ascites tumour
      cells, expressing antisense mRNA for glutaminase, contain lower levels of
      glutathione than normal ascites cells. In addition, 0.28AS-2 cells contain a
      higher number of apoptotic cells and are more sensitive to both methotrexate and
      hydrogen peroxide toxicity than normal cells. Taken together, these results
      provide insights into the role of glutaminase in apoptosis by demonstrating that
      the expression of antisense mRNA for glutaminase alters apoptosis and glutathione
      antioxidant capacity.

PMID- 15511237
TI  - Salt-inducible kinase-1 represses cAMP response element-binding protein activity
      both in the nucleus and in the cytoplasm.
AB  - Salt-inducible kinase-1 (SIK1) is phosphorylated at Ser577 by protein kinase A in
      adrenocorticotropic hormone-stimulated Y1 cells, and the phospho-SIK1
      translocates from the nucleus to the cytoplasm. The phospho-SIK1 is
      dephosphorylated in the cytoplasm and re-enters the nucleus several hours later.
      By using green-fluorescent protein-tagged SIK1 fragments, we found that a peptide
      region (586-612) was responsible for the nuclear localization of SIK1. The region
      was named the 'RK-rich region' because of its Arg- and Lys-rich nature. SIK1s
      mutated in the RK-rich region were localized mainly in the cytoplasm. Because
      SIK1 represses cAMP-response element (CRE)-mediated transcription of
      steroidogenic genes, the mutants were examined for their effect on transcription.
      To our surprise, the cytoplasmic mutants strongly repressed the CRE-binding
      protein (CREB) activity, the extent of repression being similar to that of
      SIK1(S577A), a mutant localized exclusively in the nucleus. Several chimeras were
      constructed from SIK1 and from its isoform SIK2, which was localized mainly in
      the cytoplasm, and they were examined for intracellular localization as well as
      CREB-repression activity. A SIK1-derived chimera, where the RK-rich region had
      been replaced with the corresponding region of SIK2, was found in the cytoplasm,
      its CREB-modulating activity being similar to that of wild-type SIK1. On the
      other hand, a SIK2-derived chimera with the RK-rich region of SIK1 was localized
      in both the nucleus and the cytoplasm, and had a CREB-repressing activity similar
      to that of the wild-type SIK2. Green fluorescent protein-fused transducer of
      regulated CREB activity 2 (TORC2), a CREB-specific co-activator, was localized in
      the cytoplasm and nucleus of Y1 cells, and, after treatment with
      adrenocorticotropic hormone, cytoplasmic TORC2 entered the nucleus, activating
      CREB. The SIK1 mutants, having a strong CRE-repressing activity, completely
      inhibited the adrenocorticotropic hormone-induced nuclear entry of green
      fluorescent protein-fused TORC2. This suggests that SIK1 may regulate the
      intracellular movement of TORC2, and as a result modulates the CREB-dependent
      transcription activity. Together, these results indicate that the RK-rich region
      of SIK1 is important for determining the nuclear localization and attenuating
      CREB-repressing activity, but the degree of the nuclear localization of SIK1
      itself does not necessarily reflect the degree of SIK1-mediated CREB repression.

PMID- 15511238
TI  - Cloning of two melanocortin (MC) receptors in spiny dogfish: MC3 receptor in
      cartilaginous fish shows high affinity to ACTH-derived peptides while it has
      lower preference to gamma-MSH.
AB  - We report the cloning and characterization of two melanocortin receptors (MCRs)
      from the spiny dogfish (Squalus acanthias) (Sac). Phylogenetic analysis shows
      that these shark receptors are orthologues of the MC3R and MC5R subtypes, sharing
      65% and 70% overall amino acid identity with the human counterparts,
      respectively. The SacMC3R was expressed and pharmacologically characterized in
      HEK293 cells. The radioligand binding results show that this receptor has high
      affinity for adrenocorticotropic hormone (ACTH)-derived peptides while it has
      comparable affinity for alpha- and beta-melanocyte stimulating hormone (MSH), and
      slightly lower affinity for gamma-MSH when compared with the human orthologue.
      ACTH(1-24) has high potency in a second-messenger cAMP assay while alpha- and
      gamma-MSH had slightly lower potency in cells expressing the SacMC3R. We used
      receptor-enhanced green fluorescence protein (EGFP) fusion to show the presence
      of SacMC3R in plasma membrane of Chinese hamster ovary and HEK293 cells but the
      SacMC5R was retained in intracellular compartments of these cells hindering
      pharmacological characterization. The anatomical distribution of the receptors
      were determined using reverse transcription PCR. The results showed that the
      SacMC3R is expressed in the hypothalamus, brain stem and telencephalon, optic
      tectum and olfactory bulbs, but not in the cerebellum of the spiny dogfish while
      the SacMC5R was found only in the same central regions. This report describes the
      first molecular characterization of a MC3R in fish. The study indicates that many
      of the important elements of the MC system existed before radiation of
      gnathostomes, early in vertebrate evolution, at least 450 million years ago.

PMID- 15511240
TI  - VDD pacing: under evaluated, undervalued, and underused.

PMID- 15511241
TI  - Can chest roentgenogram predict the posture dependent changes of atrial sensing
      performance in patients with a VDD pacemaker?
AB  - The VDD pacemaker is useful for sequential pacing with a single lead but carries
      a risk of sensing failure. This study was designed to evaluate the relationship
      between the relative position of atrial lead and atrial sensitivity in different
      postures in patients with VDD pacemakers. Atrial sensitivity determination and
      chest roentgenography was performed in the supine and standing position 3 months
      after implantation in 25 patients with VDD pacemakers. Measurements of cardiac
      longitudinal length (from the top of the aortic arch to the diaphragm) and
      distances from the floating electrode to the upper margin of the seventh thoracic
      vertebra (D-T7), to the top of the aortic arch (D-knob), to the lateral wall of
      right atrium (D-wall), and the D-knob/cardiac longitudinal length (D-Ratio) were
      performed. Atrial signal amplitude decreased with the standing compared to the
      supine position in eight patients (group I) and increased or did not change in
      the other 17 patients (group II). In group I, the change of the D-ratio was
      greater (0.073 vs 0.035, P < 0.01), and the change of the cardiac longitudinal
      length with standing position was greater (18.4 +/- 7.3 vs 12.1 +/- 8.8 mm, P <
      0.05) than in group II. The change of atrial sensitivity was related to the
      change of the atrial electrode position with different postures. Decreased atrial
      sensed amplitude was observed in patients who had a greater change in the cardiac
      longitudinal length while standing. Thus, a decrease in atrial sensitivity with
      standing may be predicted by the positional changes of the cardiac silhouette on
      roentgenography before the procedure.

PMID- 15511242
TI  - Atrial signal amplitude measurements in VDD systems according to body position.
AB  - Single lead VDD pacing is an established therapy in patients with AV block. Body
      position may influence the amplitude of the atrial signal recorded through the
      floating atrial electrode. This study analyzed the degree of posture related
      variation in the signal amplitude of floating atrial electrodes in 63 patients
      (mean age 72 +/- 21 years) implanted with a VDD system. The average atrial
      amplitude in the supine position was 1.59 +/- 1.15 mV and decreased significantly
      in the sitting position (1.37 +/- 1.08, P < 0.014), right decubitus (1.33 +/-
      0.83, P < 0.007), and the abdominal position (1.24 +/- 0.86, P < 0.001). The left
      side decubitus showed a nonsignificant increase in atrial amplitude (1.66 +/-
      1.02, P < 0.64). Body position significantly affects P wave amplitude and may be
      the cause of intermittent atrial undersensing. P wave amplitude measurement in
      different body postures should be performed in cases where suspected atrial
      undersensing occurs.

PMID- 15511243
TI  - Relation between the AH interval and the ablation site in patients with
      atrioventricular nodal reentrant tachycardia.
AB  - The determinants of slow pathway conduction in patients with AV nodal reentrant
      tachycardia (AVNRT) are still unknown, and great differences in the AH interval
      during slow pathway conduction are observed between patients. In 35 patients with
      typical AVNRT who underwent successful slow pathway ablation (defined as complete
      elimination of dual pathway physiology), the A2H2 interval at the "jump" during
      programmed atrial stimulation and the AH interval during AVNRT (as a reflection
      of slow pathway conduction time) and the fluoroscopic distance between the
      successful ablation site and the His-bundle recording site and between the
      coronary sinus ostium (CSO) and the His-bundle recording site were determined.
      The mean (+/- SEM) AH interval during slow pathway conduction was 323 +/- 12 ms
      with programmed stimulation and 310 +/- 10 ms during AVNRT. The mean number of
      energy applications was 8 +/- 1 (range 1-21). The mean distances between (1) the
      successful ablation site and the His bundle recording site and (2) between the
      CSO and the His-bundle recording site were 24 +/- 1 and 28 +/- 1 mm in the RAO
      and 23 +/- 1 and 28 +/- 1 mm in the LAO projections, respectively. The AH
      interval during slow pathway conduction correlated significantly with the
      distance between the successful ablation site and the His-bundle (P < 0.001) but
      not with the distance between CSO and His-bundle recording site. There is a
      significant correlation between the AH interval during slow pathway conduction
      and the distance of the successful ablation site from the His bundle. This
      relationship (1) suggests that, in addition to functional factors, anatomic
      factors influence slow pathway conduction and (2) may be helpful in determining
      the initial energy application site during slow pathway ablation.

PMID- 15511244
TI  - Long-term experience with subcutaneous ICD leads: a comparison among three
      different types of subcutaneous leads.
AB  - ICDs provide protection against sudden cardiac death in patients with life
      threatening arrhythmias. Nevertheless, efficacy of defibrillation remains an
      important issue to guarantee the future safety of patients who receive an ICD.
      There is a significant number of patients who need an additional subcutaneous
      lead to obtain a defibrillation safety margin of at least 10 J between the
      maximum output of the ICD and the energy needed for ventricular defibrillation.
      However, few data exists about the long-term performance of different types of
      subcutaneous leads. Therefore, the aim of this study was to analyze the long-term
      experience with three different types of subcutaneous leads. The study included
      132 patients (109 men, 23 women; mean age 59.8 years [SD +/- 10.7 years]). All of
      them received a subcutaneous lead in addition to a single chamber or dual chamber
      ICD between October 1990 and April 2002. Two patients received a second
      subcutaneous lead after the first lead had been removed so that a total of 134
      subcutaneous leads were evaluated. Inclusion criteria for the implantation of an
      additional subcutaneous lead were (1) unsuccessful ventricular defibrillation at
      implant without a subcutaneous lead, (2) insufficient safety margin (< 10 J)
      between the maximum output of the ICD and the energy needed for ventricular
      defibrillation, or (3) clinical evaluation of a new subcutaneous lead (Medtronic
      13014). There were no significant differences between the three study groups with
      regard to age, sex, underlying cardiac disease, left ventricular ejection
      fraction, NYHA class assessment and clinical arrhythmia. The results of the DFT
      testing during follow-up (prehospital discharge test and 1 and 3 years) were
      compared to the baseline value obtained during the implantation procedure. All
      lead related complications were analyzed. Eighty-two single element subcutaneous
      array electrodes (SQ-A1), 31 subcutaneous three-finger electrodes (SQ-A3), and 21
      subcutaneous patch electrodes (SQ-P) were implanted during the study period. The
      median follow-up was 1,499 days (25th percentile: 798 days, 75th percentile:
      1,976 days) in the SQ-A1 group, 2,209 days (25th percentile: 1,242 days, 75th
      percentile: 2,710 days) in the SQ-A3 group, and 1,419 days (25th percentile: 787
      days, 75th percentile: 2,838 days) in the SQ-P group. None of the three groups
      had a significant change of the DFT during follow-up compared to baseline. Major
      complications occurred in six (7.3%) patients in group SQ-A1 and in two (9.5%)
      patients in group SQ-P. There were no major complications in group SQ-A3. Kaplan
      Meier curves analyzing freedom from subcutaneous lead related complications did
      not show a significant difference between the three study groups (P = 0.16). SQ
      A1, SQ-A3, and SQ-P leads provide stable DFTs during long-term follow-up. Major
      complications are rare. However, a careful follow-up including chest radiographs
      at regular intervals is needed to detect potentially fatal complications like
      lead fractures.

PMID- 15511245
TI  - Pulmonary vein stenosis and remodeling after electrical isolation for treatment
      of atrial fibrillation: short- and medium-term follow-up.
AB  - Asymptomatic pulmonary vein (PV) stenosis after PV electrical isolation for
      atrial fibrillation has been reported in several studies and may be due to
      dynamic factors. The purpose of this study was to determine if PV stenosis
      progresses after the initial procedure. Consecutive patients (n = 26) requiring
      repeat procedures for atrial fibrillation recurrence were studied (mean age 55 +/
      12 years). Segmental PV potential-guided ostial ablation was performed with
      transvenous catheters. Biplane angiographic images were obtained before and after
      each procedure (52 procedures). Stenoses were found in 14 (16%) of 87 targeted
      veins immediately after the initial procedures. After 129 +/- 94 days no new
      stenoses were found at the second procedure. PV stenoses were unchanged in 8
      previously stenosed veins, slightly deteriorated in 1 vein, improved in 2 veins,
      and fully resolved in 3 veins. No patients had symptoms attributable to PV
      stenosis. PV stenosis occurred in 6 (9%) of 68 additional veins at the second
      procedure. No baseline or procedural characteristics predicted stenosis.
      Progression of PV stenosis is uncommon in the medium term. Complete or partial
      resolution of PV stenosis occurs in approximately one third of cases. Absence of
      PV stenosis after an initial procedure does not ensure PV stenosis will not occur
      with further ablation in the same vein.

PMID- 15511246
TI  - Autonomic nervous system changes in vasovagal syncope: is there any difference
      between young and older patients?
AB  - Spectral analysis of heart rate variability was used to compare the changes in
      autonomic function during tilting in young and older patients with vasovagal
      syncope. Twenty-four young (age 28 +/- 8 years) and 31 older (56 +/- 5 years)
      patients with unexplained syncope and a positive tilt test and 25 controls (age
      48 +/- 12 years) were included in the study. Frequency-domain measurements of the
      low (LF) (0.06-0.15 Hz) and high (HF) (0.15-0.40 Hz) frequency bands and the
      ratio of LF to HF were computed from Holter recordings for 4-minute intervals
      before and immediately after tilting and just before the end in all groups.
      Syncopal patients showed a different pattern of response to tilting from controls
      in all spectral indexes. Young and older patients showed the same pattern of
      changes in all measurements, even though certain differences were observed. The
      LF after tilting reduced more in the older (-20 +/- 7% vs -14 +/- 5%, P < 0.001),
      while HF reduced more in young patients (-17 +/- 8% vs -8 +/- 3%, P < 0.001).
      Young patients showed mainly a cardioinhibitory type (71%) of response whereas a
      vasodepressor type response predominated (68%) in the older patients. The
      autonomic nervous system appears to play an important role in the
      pathophysiological mechanism of vasovagal syncope. This role is similar in young
      and in older patients and this should be taken into account in the therapeutic
      approach to the condition. Specific differences between age groups may be related
      to the type of vasovagal syncope.

PMID- 15511247
TI  - Principal component analysis of the T wave in patients with chest pain and
      conduction disturbances.
AB  - There is a need for markers reflecting the increased risk in patients with
      conduction disturbances. Conduction disturbances presumably cause inhomogeneous
      repolarization that may create an arrhythmogenic substrate. In patients with
      normal conduction, parameters derived from principal components analysis (PCA) of
      the T wave contain prognostic information. The nondipolar PCA components are
      assumed to reflect repolarization inhomogeneity. This study examined the PCA
      parameters in relation to conduction disturbances. PCA was performed on
      continuously recorded 12-lead ECGs in 800 patients with chest pain and
      nondiagnostic ECG on admission. The patients with conduction disturbance on
      admission were classified into separate groups and related to comparison groups
      without conduction disturbance recruited from the same series. For each patient,
      the dipolar and nondipolar components were quantified by medians of the ratio of
      the two largest eigenvalues (S2/S1 Median), the residue that summarizes the
      eigenvalues S4-S8 (TWRabsMedian) and the ratio of this residue to the total power
      of the T wave (TWRrelMedian). The parameters were assessed with respect to common
      clinical and ECG parameters, discharge diagnosis, and total mortality during a 35
      month follow-up. TWRabsMedian increased with increasing conduction disturbance.
      In 135 patients with conduction disturbances, ROC curves for TWRabsMedian as
      indicator of mortality exhibited areas under a curve of 0.66, 0.65, and 0.56 at 6
      month, 24-month, and 35-month follow-up. Conduction disturbances were associated
      with increased nondipolar PCA component and, thus, with increased repolarization
      inhomogeneity. The nondipolar PCA component contained a moderate amount of
      prognostic information not present in a simple ECG diagnosis of a conduction
      disturbance.

PMID- 15511248
TI  - Usability assessment of pacemaker programmers.
AB  - There is a perception among clinicians of usability differences in the user
      interface of pacemaker programmers, but there is an absence of literature in this
      area. The purpose of this study was to describe usability differences in
      pacemaker programmers. Forty-two programmer users completed self-administered
      questionnaires and two usability experts independently performed heuristic
      evaluation to identify features that violated general usability principles.
      Programmers from seven manufacturers (coded A-G) were evaluated. There was a
      balanced representation of users: nurses (58%) versus technologists (40%) who are
      employed in community (50%) versus academic (45%) hospitals, novice versus expert
      users based on the median users' programming experience of 60 months (range 1-300
      months). Significant differences between programmers were found in overall user
      satisfaction and ease of programmer use (P < 0.0001) in the display, controls,
      operation, and physical dimension of the programmers (P < 0.05). Heuristic
      evaluations showed frequent violations of usability principles in all
      programmers. Problematic areas include reliance on user recall, inconsistency in
      operation of critical controls, poor readability, and not anticipating user wants
      or action. Programmer interface designs do not consistently meet user needs or
      general usability principles. This impacts on the safe and effective use of
      programmers. Guidelines in programmer design should be established, particularly
      with respect to labeling, location, and operation of critical controls.

PMID- 15511249
TI  - Long-term performance of transvenous, steroid-eluting, high impedance, passive
      fixation ventricular pacing leads.
AB  - The long-term performance of two high impedance, steroid-eluting, passive
      fixation ventricular leads, porous platinum iridium electrode CPI Selute Picotip
      4035 (131 patients), and platinized platinum electrode Medtronic Capsure Z 5034
      (57 patients), was compared with one conventional 8.0-mm2 porous platinum iridium
      electrode CPI Selute 4285 (38 patients). The mean follow-up period was 28 +/- 14
      months. Capture threshold, R wave amplitude, and pacing impedance were measured
      at the time of implantation, immediately after implantation, 1 week, 1, 3, and 6
      months after implantation and then every 6 months thereafter. The two high
      impedance leads revealed a higher sensing slew rate than the conventional lead,
      the R wave amplitude was similar among the three groups, but the voltage
      threshold at 0.5-ms pulse width was significantly higher in porous platinum
      iridium groups at the time of implantation. During follow-up, the conventional
      lead revealed a significantly higher R wave amplitude within the first 3 months,
      however, this pattern disappeared after 3 months. Pacing impedance was
      significantly higher in the high impedance porous platinum iridium electrode
      groups. Voltage threshold at 0.5-ms pulse width was similar among the three
      groups in the first 3 months, however, it increased gradually and was
      significantly higher in porous platinum iridium electrode groups subsequently.
      The energy threshold at 0.5 ms was significantly lower in the two high impedance
      groups than the conventional group, but no difference was found in the two high
      impedance groups. Lead related complications were similar among the three groups.
      In conclusion, high impedance electrodes with different design and materials had
      different properties; platinized platinum electrode showed a lower pacing
      impedance but had a more stable long-term capture threshold as compared to the
      porous platinum iridium electrode. Further studies are mandatory for the
      development of an ideal pacing lead.

PMID- 15511250
TI  - The role of angiotensin receptor blockers and/or angiotensin converting enzyme
      inhibitors in the prevention of atrial fibrillation in patients with
      cardiovascular diseases: meta-analysis of randomized controlled clinical trials.
AB  - The inhibition of the renin-angiotensin system has demonstrated both experimental
      and clinical effects in preventing atrial fibrillation. However, there is still
      uncertainty about the role of these drugs in clinical practice. The objective of
      this review has been to assess the effects of angiotensin II type-1 receptor
      blockers (ARBs) and/or angiotensin converting enzyme inhibitors (ACEIs) for
      preventing atrial fibrillation. We searched the Cochrane controlled Trials
      Register (Cochrane Library Issue 4, 2002), MEDLINE (January 1980 to November
      2003), EMBASE (January 1980 to November 2003) and reference list of articles. We
      also contacted manufacturers and researchers in the field. SELECTION CRITERIA: We
      conducted a meta-analysis of all randomized controlled clinical trials that
      compared ARBs and/or ACEIs with either placebo or conventional therapy in
      patients with either hypertension, heart failure, ischemic heart disease, or
      diabetes mellitus. The pooled outcome was the development of new onset atrial
      fibrillation. Two reviewers independently assessed trial quality and extracted
      data. In some cases, the study authors were contacted for additional information.
      Seven trials involving a total of 24,849 patients were included (11,328
      randomized to active therapy and 13,521 to control). There was a significant
      statistical difference in the pooled development of atrial fibrillation between
      the treatment and control group. (OR, 0.57; 95% CI, 0.39 to 0.82); test for
      overall effect z = 2.98 P = 0.003). Treatment with ACEIs/ARBs markedly reduces
      the risk of development or recurrence of atrial fibrillation.

PMID- 15511251
TI  - Persistence of septal defects after transeptal puncture for pulmonary vein
      isolation procedures.
AB  - Pulmonary vein isolation (PVI) is widely practiced as a means of potentially
      curing atrial fibrillation (AF). Transeptal puncture is performed for PVI
      procedures, often two such punctures are performed. We sought to examine the
      prevalence of medium- to long- term iatrogenic septal defects after such
      procedures. Thirty-one patients who were undergoing their second PVI procedure
      were studied with transesophageal echocardiography (TEE) with two-dimensional
      imaging and color Doppler, examining the fossa ovalis for defects. Mean time from
      the original PVI to the time of TEE was 35 weeks. Two patients were discovered to
      have iatrogenic septal defects. The interval between the first PVI procedure and
      the TEE showing a septal defect was 33.7 weeks in one patient and 14.3 weeks in
      the other. Iatrogenic septal defects may occur in the medium- to long-term in
      patients undergoing PVI procedures for AF. The clinical implications of such
      defects are unknown.

PMID- 15511252
TI  - Sudden intense exercise increases QT heart rate slope and T wave complexity in
      long QT syndrome and normal subjects.
AB  - Sudden intense physical activity is a trigger for ventricular arrhythmias in long
      QT syndrome (LQTS), and beta-blockers (B) reduce the risk of ventricular
      arrhythmias in LQTS. We compared the effect of graded (gradual intensity) versus
      burst (sudden intensity) exercise on QT-rate adaptation and T wave complexity in
      LQTS + B (n = 21), LQTS - B (n = 5), and normal controls (n = 20). Graded
      exercise consisted of symptom-limited bicycle ergometry (30 W, increment 20
      W/min). Burst exercise involved a fixed 200 W load for 1.0 minute. ECGs were
      digitally recorded every 10 seconds during exercise and a 10 minute recovery
      period. QT-rate adaptation was quantified using the slope of the QT cycle length
      relationship fit to a quadratic function. Principle component analysis (PCA) was
      used to quantify T wave complexity. The QT-rate slope was two-fold greater with
      burst exercise than graded exercise for LQTS + B (-82E +/- 40E vs -36E +/- 40E, P
      = 0.0016), LQTS - B (-85E +/- 60E vs -30E +/- 50E, P = 0.011) and controls (-100E
      +/- 60E vs -48E +/- 100E, P = 0.0011) (E = x10(-5)). For each exercise protocol,
      there was no difference in QT-rate slope between the three groups. In contrast,
      the QT-rate slope during the 10 minute recovery period was similar between the
      burst and graded protocol for LQTS + B (25E +/- 40E vs 30E +/- 50E), LQTS - B
      (81E +/- 80E vs 85E +/- 70E) and controls (90E +/- 80E vs 82E +/- 80E). The
      coefficient of variability of PCA (T wave complexity variability) during burst
      exercise was greater than that during graded exercise for LQTS + B (41 +/- 15 vs
      30 +/- 10, P = 0.017), LQTS - B (47 +/- 25 vs 26 +/- 4, P = 0.016), and control
      (46 +/- 14 vs 33 +/- 19, P = 0.012). For each exercise protocol, no difference in
      T wave complexity variability was seen between the three groups. In conclusion,
      QT heart rate slope and T wave complexity variability are greater during sudden
      intense exercise than graded exercise in LQTS patients (on and off beta-blockers)
      and normal subjects, with similar findings among the three groups of patients.

PMID- 15511253
TI  - Ectopy and wide QRS tachycardia: what is the mechanism?

PMID- 15511254
TI  - Ablation of isthmus dependent atrial flutter: when to call for the next patient.

PMID- 15511255
TI  - Positional ventricular tachycardia.
AB  - A 60-year-old man showed nonsustained repetitive monomorphic VT in the left
      lateral position, but this was terminated by deep inspiration. Echocardiography
      and MRI demonstrated a false tendon extending from the apex to the basal septum
      where the VT could have originated. Spontaneous remission occurred during the 16
      year follow-up.

PMID- 15511256
TI  - Successful catheter ablation of atrial tachycardia originating near the
      atrioventricular node from the noncoronary sinus of Valsalva.
AB  - This report describes a patient who underwent RF catheter ablation of atrial
      tachycardia. Two applications of RF energy near the His-bundle region transiently
      terminated the tachycardia. With detailed mapping at the aortic sinus of Valsalva
      using a retrograde transaortic approach, the earliest atrial activation was found
      in the noncoronary sinus of Valsalva. Complete elimination of the tachycardia was
      achieved with RF energy application from this site.

PMID- 15511257
TI  - Right phrenic nerve injury following electrical disconnection of the right
      superior pulmonary vein.
AB  - This report describes a case of transient paresis of the right diaphragm
      following the transcatheter radiofrequency ablation for the electrical
      disconnection of pulmonary veins, which recovered completely during the
      observational period in a 61-year-old woman with paroxysmal atrial fibrillation.
      For electrical disconnection of pulmonary veins, careful preventive measures for
      phrenic nerve damage are required.

PMID- 15511258
TI  - Alleviation of central sleep apnea by ventricular pacing in a patient with an
      implanted cardioverter defibrillator.
AB  - A 75-year-old man with a single chamber cardioverter defibrillator implanted for
      the management of sustained ventricular tachycardia developing after a healed
      myocardial infarction was admitted for evaluation of a sleep disorder.
      Polysomnography confirmed the presence of severe predominant central sleep apnea
      syndrome. The apnea-hypopnea index score decreased from 43.3 during spontaneous
      cardiac rhythm to 24.6 during VVI pacing at a rate of 70 beats/min. Ventricular
      pacing reduced the number of episodes of central sleep apnea/hypopnea without
      reducing the total sleep time, though it had no effect on episodes of obstructive
      sleep apnea/hypopnea.

PMID- 15511259
TI  - Gatifloxacin induced torsades de pointes.
AB  - The authors present an unusual case of torsades de pointes in an elderly woman
      treated with intravenous gatifloxacin antibiotic therapy.

PMID- 15511260
TI  - Dual site coronary sinus pacing in a patient with an artificial tricuspid valve
      prosthesis.
AB  - For safety reasons, two leads for left ventricular pacing were implanted in the
      coronary sinus of a pacemaker dependent patient with an artificial tricuspid
      valve prosthesis.

PMID- 15511261
TI  - Malfunction of a biventricular pacing device?
AB  - A patient with dilated cardiomyopathy and recurrent admissions for heart failure
      presented 3 days after implantation of a biventricular pacemaker to the emergency
      department. Due to significant bradycardia, he was initially diagnosed with
      pacemaker malfunction. Subsequent interrogation of the device revealed a normally
      functioning biventricular pacemaker. After treating his underlying medical
      problems, the electrocardiogram returned to baseline.

PMID- 15511262
TI  - A simpler solution to the old problem of frozen leads.
AB  - Pacemaker generator replacement is usually a straightforward and simple
      procedure. However, it is occasionally complicated by entrapment of the lead in
      the header. Solutions to this problem have been described previously. We describe
      a simpler and safer technique to solve this old problem.

PMID- 15511263
TI  - Leads frozen in the header: a real problem or just many solutions?

PMID- 15511266
TI  - Subpectoral devices.

PMID- 15511268
TI  - Secondary effects induced by the colon carcinogen azoxymethane in BDIX rats.
AB  - Azoxymethane (AOM) is claimed to be a colon-specific carcinogen. In our studies,
      AOM was administered to adult BDIX/OrlIco rats by four weekly subcutaneous
      injections of 15 mg/kg body weight each - two periods of 2 weeks of AOM treatment
      separated by a one-week break. This treatment schedule resulted in colon
      carcinomas with a high frequency (75-100%) and with a high reproducibility.
      However, some serious side effects are associated with this carcinogen treatment.
      In addition to the colorectal tumours, we found small intestinal tumours, hepatic
      lesions and a high frequency of mesenchymal renal tumours which increased with
      longer latency periods. The renal tumours were only found in female rats, and
      this indicates a possible relation to sex hormones. We therefore analyzed both
      male and female kidneys for the expression of estrogen and progesterone receptors
      by immunohistochemical methods. A positive nuclear reaction for estrogen receptor
      was present in most tumour cells in all tumours and occasionally in nuclei of
      entrapped tubular cells, but never in glomeruli. Normal appearing renal tissue
      from female rats showed no positive reaction, but in male rats a slight nuclear
      reaction was seen in tubuli in the peripheral part of the medulla. A similar
      pattern was seen for progesterone receptors, but less pronounced. No rats
      developed tumours in the external ear canal, which is in contrast to studies
      performed in other rat strains. This may therefore be strain related. In order to
      reduce the secondary effects of the induction of colon cancer by AOM, it is
      advisable to use male rats only and a maximum latency period of 32 weeks.

PMID- 15511269
TI  - Loss of caspase-2, -6 and -7 expression in gastric cancers.
AB  - Caspases play an essential role during apoptotic cell death, and alterations of
      caspases are known to contribute to human cancer development. In the current
      study, we analyzed the expression of caspase-2, -6 and -7 in 120 gastric
      carcinomas by immunohistochemistry using a tissue microarray approach. Caspase-2,
      -6 and -7 were expressed in 42 (35%), 63 (53%) and 39 (33%) of the gastric
      cancers, respectively. By contrast, the surface mucous cells and mucosal
      glandular cells in the normal gastric mucosa showed strong immunoreactivity for
      caspase-2, -6 and -7. Taken together, these results indicate that caspase-2, -6
      and -7 expression in gastric cancer cells is decreased compared to in normal
      gastric mucosal cells, and suggest that loss of caspase-2, -6 and -7 expression
      might be involved in the mechanisms of gastric cancer development.

PMID- 15511270
TI  - Identification of Bartonella species in rodents, shrews and cats in Denmark:
      detection of two B. henselae variants, one in cats and the other in the long
      tailed field mouse.
AB  - Small mammals and stray cats were trapped in two areas of North Zealand, Denmark,
      and their blood cultured for hemotrophic bacteria. Bacterial isolates were
      recovered in pure culture and subjected to 16S rDNA gene sequencing. Bartonella
      species were isolated from five mammalian species: B. grahamii from Microtus
      agrestis (field vole) and Apodemus flavicollis (yellow-necked field mouse); B.
      taylorii from M. agrestis, A. flavicollis and A. sylvaticus (long-tailed field
      mouse); B. tribocorum from A. flavicollis; B. vinsonii subsp. vinsonii from M.
      agrestis and A. sylvaticus; and B. birtlesii from Sorex vulgaris (common shrew).
      In addition, two variant types of B. henselae were identified: variant I was
      recovered from three specimens of A. sylvaticus, and B. henselae variant II from
      11 cats; in each case this was the only B. henselae variant found. No Bartonella
      species was isolated from Clethrionomys glareolus (bank vole) or Micromys minutus
      (harvest mouse). These results suggest that B. henselae occurs in two animal
      reservoirs in this region, one of variant I in A. sylvaticus, which may be
      transmitted between mice by the tick Ixodes ricinus, and another of variant II in
      cats, which may be transmitted by the cat flea (Ctenocephalides felis). To our
      knowledge, this is the first report of the occurrence of B. henselae and B.
      tribocorum in Apodemus mice.

PMID- 15511271
TI  - DNA extraction and PCR assays for detection of Toxoplasma gondii.
AB  - For detection of Toxoplasma gondii we compared the sensitivity of two different
      DNA extraction methods and three different PCR assays. Sensitivities of DNA
      extraction by QIAamp DNA mini Kit or MagNa pure followed by PCR, nested PCR and
      oligochromatography or Light Cycler PCR using either SYBR green chemistry or
      TaqMan probe were compared. No significant difference between extraction methods
      was found using pure T. gondii tachyzoites. Spiked blood samples, 10(4) to 10
      parasites per sample, generated no difference in sensitivity between the two DNA
      extraction methods when analysed by nested PCR detected by oligochromatography or
      analysed by Light Cycler PCR TaqMan. In spiked blood samples Light Cycler PCR
      SYBR green was unable to detect the parasite and a reduction in sensitivity was
      observed with the TaqMan assay. Conventional PCR was more sensitive when DNA was
      extracted from the spiked samples using the QIAamp DNA mini Kit. Conventional and
      nested PCR were found to be more sensitive than Light Cycler PCR TaqMan using the
      QIAamp DNA mini Kit. It was not possible to use Light Cycler PCR SYBR green in
      blood samples. Conventional PCR was more sensitive for detection of T. gondii in
      spiked blood samples using QIAamp DNA mini Kit DNA extraction, suggesting that
      the choice of DNA extraction method may affect PCR assays differently.

PMID- 15511272
TI  - The associations of obesity, lymph node status and prognosis in breast cancer
      patients: dependence on estrogen and progesterone receptor status.
AB  - Breast cancer patients who are obese have a higher risk of lymph node metastases
      and a poorer prognosis than those who are slim. It has been claimed that
      estrogens derived from fat are important for these associations. If estrogens are
      important, these relationships must be stronger in the hormone receptor-positive
      than in the hormone receptor-negative groups. Body mass index (BMI) was used as a
      measure of obesity. The second, third, and fourth quintiles of BMI were treated
      as one group and termed 'medium'. Patients in the fifth quintile were termed
      'obese' and those in the first quintile 'slim'. The number of women with
      unilateral disease treated with modified radical mastectomy and included in the
      study was 1211. Of all patients included, obese patients had a 1.53 higher risk
      of lymph node metastases compared to slim patients (p=0.02). In the PgR-negative
      group, obesity gave a 3.08 times higher risk of lymph node metastases (p=0.03).
      The risk of dying of breast cancer tended to be higher in obese than in slim
      patients when all patients in the study were compared (relative risk=1.38,
      p=0.06). BMI did not show a statistically significant relationship with prognosis
      if only hormone receptor status was considered. However, if lymph node status and
      hormone receptor status were taken together, the association was strong and
      reversed in the lymph node-positive group with ER-negative tumours. The adjusted
      relative risk was 0.33, showing that slim patients had a 3.03 (1.0/0.33) times
      higher risk of dying of breast cancer compared to obese patients (p=0.002). These
      results indicate that non-hormonal mechanisms could be important.

PMID- 15511273
TI  - The expression and activity of renal nitric oxide synthase and circulating nitric
      oxide in polycystic kidney disease rats.
AB  - Nitric oxide (NO) influences tubular fluid and electrolyte transport, and hence
      possibly also fluid accumulation in renal cysts. The expression and activity of
      intrarenal constitutive NO synthase (cNOS) [neuronal NOS, nNOS and endothelial
      NOS, eNOS] and inducible NOS (iNOS) and plasma nitrite/nitrate (PNOx)
      concentration were assessed in homozygous Han:SPRD polycystic kidney disease
      (PKD) rats (cy/cy), heterozygous Han:SPRD PKD rats (cy/+), homozygous normal
      Han:SPRD littermates (+/+) and Sprague Dawley rats (sd). The results showed: 1)
      nNOS expression was decreased in proximal tubules and thick ascending limbs of
      the loop of Henle in cy/cy and cy/+ rats compared to +/+ and sd rats (p<0.05).
      nNOS was weakly expressed in the epithelium of small cysts and unexpressed in
      epithelium of large cysts. 2) iNOS expression was increased in proximal tubular
      epithelial cells in cy/+ rats compared to +/+ rats and sd rats (p<0.01). iNOS
      expression in cyst epithelium was decreased in cy/+ rats (p<0.05) and absent in
      cy/cy rats. 3) eNOS expression was similar in the endothelium of intrarenal
      arteries in all groups. 4) The activity of renal cNOS was decreased in cy/cy and
      cy/+ rats; the activity of iNOS was decreased only in cy/cy rats, with no
      significant difference among the other three groups. 5) PNOx concentration was
      higher in cy/cy rats than in the other three groups, and correlated positively
      with plasma creatinine and urea. In conclusion, NOS expression and activity
      decreased as cysts developed, suggesting that NO downregulation is involved in
      the pathogenesis of PKD.

PMID- 15511274
TI  - Ginseng modulates the immune response by induction of interleukin-12 production.
AB  - In infections with intracellular microorganisms such as mycobacteria and
      Leishmania parasites as well as certain extracellular chronic infections such as
      Pseudomonas aeruginosa a Th1 response with activation of macrophages is
      desirable. Several studies indicate that such a response is associated with
      better recovery from infection, improved course of the chronic infection, and
      higher survival rate. In Th1 responses there is increased interferon-gamma (IFN
      gamma) and interleukin-12 (IL-12) production, whereas that of interleukin-10 (IL
      10) is decreased. The present study indicated that Ginseng modulation of
      stimulated peripheral blood mononuclear cells (PBMC) results in a higher IL-12
      production. The enhanced IL-12 production could induce a stronger Th1 response,
      resulting in better protection against infection with a variety of pathogens.

PMID- 15511275
TI  - Activity of hydrolytic enzymes in fungi isolated from diabetic pregnant women: is
      there any relationship between fungal alkaline and acid phosphatase activity and
      glycemic control?
AB  - Ability to respond to environmental changes and secretion of hydrolases are
      considered to be important for Candida virulence. In this study we determined and
      compared the activities of 19 different hydrolases of the fungal strains isolated
      from diabetic and non-diabetic pregnant women. We also looked for the presence of
      a relationship between hydrolase activities and glycemic control, and,
      furthermore, evaluated the influence of gestational age on the activity of
      hydrolases. Mycological examinations were performed for 119 diabetic pregnant
      women: 47 with diabetes mellitus type I (DM), 72 with gestational diabetes (GDM),
      and for 132 healthy women (CON). Samples were collected from the vagina, rectum
      and oral cavity and cultured on Sabouraud media. The fungal hydrolase activities
      were evaluated using the API ZYM test (bioMerieux). For the 19 different fungal
      hydrolases tested, 13 activities were present in the isolated fungal strains. The
      activity of alkaline phosphatase (ALP) in vaginal strains (p=0.028) and acid
      phosphatase (ACP) in strains from the vagina (p=0.006) and rectum (p=0.049) was
      significantly lower in DM than in GDM and CON women. In conclusion, we describe
      for the first time that fungi isolated from pregnant diabetic women have lower
      activity of both phosphatases compared to fungi isolated from healthy women.
      Furthermore, similar differences of mean ALP and ACP activities were observed in
      the course of pregnancy in strains from the vagina and rectum of DM and CON
      women. However, strains from DM had lower activity at each stage of pregnancy.
      The highest activity of ALP and ACP was detected at the beginning, then declined,
      and had the lowest values between the 24(th) and 33(rd) week of gestation. After
      that period the activity of both phosphatases increased.

PMID- 15511276
TI  - Mesenchymal chondrosarcoma of the thyroid -- a rare tumour at an unusual site.
AB  - We describe the light microscopic, immunohistochemical and ultrastructural
      features of the first case in the literature of a primary mesenchymal
      chondrosarcoma (MC) of the thyroid and discuss its differential diagnosis at
      unusual extraskeletal sites. A nodular lesion of the thyroid with no evidence of
      extrathyroid disease showed the bimorphic pattern and haemangiopericytoma-like
      areas typical of MC. In the undifferentiated areas, the cells were CD99
      positive/CD117 negative, while the stroma showed focal positivity for alpha
      inhibin. In spite of its rarity, it is important to diagnose primary mesenchymal
      chondrosarcoma in a parenchymatous organ such as the thyroid because its
      biological behaviour may be different from that of tumours of similar morphology
      and complete resection is the treatment of choice. The patient is free of disease
      nearly 66 months after its first presentation. Cytogenetic and immunohistological
      markers may play important roles in diagnosis of this lesion in future,
      especially with limited tissue samplings; however, for the present a thorough
      sampling of the tumour remains the best diagnostic strategy.

PMID- 15511277
TI  - Expression of adhesion molecules and Ki-67 in female adnexal tumor of probable
      Wolffian origin (FATWO): report of two cases and review of the literature.
AB  - Female adnexal tumor of probable Wolffian origin (FATWO) is a rare entity which
      is believed to originate from mesonephric (Wolffian) remnants on the basis of its
      location where the remnants are abundant. Its behavior is usually indolent,
      although some cases can recur or metastasize. The authors present the
      clinicopathological features of two cases of FATWO arising in the broad ligament,
      and focus on the expression of adhesion molecules and proliferative marker.
      Mesonephric duct remnants are also examined in an attempt to elucidate the
      histogenesis of FATWOs. The two FATWOs were well-circumscribed solid masses
      arising in the leaves of the broad ligament and histological examination revealed
      a mixture of cysts and tubules imparting a sieve-like pattern and mucin-negative
      eosinophilic secretion within these tubules. Immunohistochemically, the tumors
      showed the expression of cytokeratin 7 and 20, high-molecular-weight cytokeratin,
      and calretinin, which closely resembled that of the mesonephric duct remnants.
      Regarding CK 20, CD 10, EMA, S-100 protein, and vimentin their expression was in
      part not identical with previous studies. E-cadherin, alpha and beta-catenin were
      strongly expressed along the cell membrane of the tumor cells. The Ki-67 labeling
      index of FATWO was 0% and 3.2% in each case. The preservation of the E-cadherin
      catenin complex and low Ki-67 labeling index could explain the indolent behavior
      and low malignant potential of this tumor.

PMID- 15511278
TI  - Effect of orally administered hydrocortisone on intraocular pressure in
      nonglaucomatous dogs.
AB  - OBJECTIVE: To determine the effect of oral hydrocortisone on intraocular pressure
      (IOP) in ocular normotensive dogs. ANIMALS STUDIED: Seventeen ocular normotensive
      dogs. Procedures Dogs were randomly assigned to treatment (n = 9) and control (n
      = 8) groups. Dogs in the treatment group received hydrocortisone, 3.3 mg/kg PO
      every 8 h, and dogs in the control group received gelatin capsule placebo PO
      every 8 h for 5 weeks. Applanation tonometry was performed on both eyes of all
      dogs prior to treatment and then once weekly for 5 weeks during hydrocortisone
      treatment. RESULTS: No significant effect of treatment was noted for right (P =
      0.1013) or left (P = 0.1157) eyes during the treatment period, nor was there
      significant interaction of treatment by week for the right (P = 0.9456) or left
      (P = 0.3577) eyes. A significant rise in IOP over the treatment period was noted
      in both right (P < 0.0001) and left (P = 0.0006) eyes of both groups, but was
      unrelated to treatment. CONCLUSION: Orally administered hydrocortisone does not
      significantly increase IOP in nonglaucomatous dogs when administered over a 5
      week period.

PMID- 15511279
TI  - Effects of trimethoprim-sulfadiazine on tear production and the fluctuations of
      Schirmer tear test values in horses.
AB  - The objectives of this study were to observe the effects of trimethoprim
      sulfadiazine on equine tear production and to determine normal fluctuations in
      Schirmer tear test (STT) values in horses. A randomized, placebo-controlled,
      blinded clinical trial measuring STT values in 15 horses over an 8-week period
      was performed. The treatment group (eight horses) received 30 mg/kg trimethoprim
      sulfadiazine orally once a day and the control group (seven horses) received
      placebo (flour) at the same time. All horses were housed outdoors throughout the
      study. Schirmer tear test values were measured at 0, 2, 4, 6 and 8 weeks, and 4
      weeks after discontinuation of treatment. There were no significant differences
      in tear production between the treated and control groups. Fluctuations in STT
      were observed and may result from individual and environmental variations.
      Trimethoprim-sulfadiazine did not decrease tear production in the horses in this
      study. Horses normally experience periodic fluctuations in STT values.

PMID- 15511280
TI  - Fundus pigment distribution in rhesus monkeys.
AB  - There is growing evidence for an interaction among fundus pigmentation,
      character, geography and the function and structure of the outer retina. We
      examined three inbred groups of rhesus macaques (132 eyes) including all ages.
      One was a smaller (18 eyes) group. Coat colors were variations of brown-tan
      however, the smaller group had lighter 'golden' coats and colors. Fundus images
      were classified for pigmentation and its geographic distribution. In golden
      coated animals there was bias toward nasal fundus hypopigmentation with the optic
      disk as a watershed demarcation zone, which extended in the superior-inferior
      direction. Temporal fundus hypopigmentation did not occur in the absence of nasal
      hypopigmentation. More common, darker coated samples showed a characteristic
      diffuse fundus pigmentation. There was no evidence for albinism or large
      variations in macular pigmentation. Rhesus monkeys can exhibit geographically
      controlled genetic development of fundus pigmentation. Hypopigmentation provides
      for access to the choroidal infrastructure.

PMID- 15511281
TI  - Profiles of matrix metalloproteinase activity in equine tear fluid during corneal
      healing in 10 horses with ulcerative keratitis.
AB  - OBJECTIVE: Levels of tear film matrix metalloproteinases (MMPs) activity are
      significantly elevated in horses with ulcerative keratitis and contribute to the
      excessive breakdown of stromal collagen. Changes in the amount of proteolytic
      activity in horse tear film during corneal healing and stromal remodeling have
      not yet been reported, but we hypothesize they should decrease. In the present
      study we analyzed serial tear fluid from horses with ulcerative keratitis to
      identify any changes in MMP activity during corneal healing and stromal
      remodeling. PROCEDURES: Samples of tear fluid were obtained from both eyes of 10
      horses with ulcerative keratitis on the day of admission (day 1) at the hospital
      and then at various time points until complete healing of the cornea. Tear film
      MMP2 and MMP9 activity was determined by quantitative gelatin zymography. In all
      cases medical treatment included topical applications of equine serum,
      antibiotics, atropine and systemic administration of anti-inflammatory drugs.
      Surgical procedures were performed in several cases on day 2 in addition to the
      medical treatment. RESULTS: The mean total MMP activity (+/- SD) measured in
      relative standard units (RSU) in the tear fluid of the ulcerated eye (2.44 +/-
      1.44) of the 10 horses was significantly higher than the mean in the
      contralateral eye (0.81 +/- 0.68) (P = 0.006), on the day of admission at the
      VMTH. The mean MMP activity in these ulcerated eyes significantly decreased (
      82.4%) between the first day of admission and the day when the ulcer had
      completely healed (P = 0.0002). The activity level in the healed eye (0.43 +/-
      0.17) was not significantly different to the one in the contralateral eye (0.36
      +/- 0.18) on the day of complete corneal healing (P = 0.374). The level of MMP
      activity in the contralateral eye also decreased from 0.81 +/- 0.68-0.36 +/- 0.18
      but this decrease (56%) was not significant (P = 0.069). CONCLUSIONS: Ulcerative
      keratitis in horses is associated with initially high levels of tear film
      proteolytic activity that decrease as the ulcers heal. The success of medical and
      surgical treatment of the corneal ulcers is reflected by the enzyme activity in
      tears. In horses successful treatment does lead to a rapid reduction in tear film
      proteolytic activity that corresponded with the improvement in the clinical signs
      of corneal ulceration. Measurement of MMP activity in the tear film might
      represent a way to monitor the progression of corneal healing in horses with
      ulcerative keratitis.

PMID- 15511282
TI  - Malignant teratoid medulloepithelioma with brain and kidney involvement in a dog.
AB  - ANIMAL STUDIED: A tumor of the left eye with involvement of the brain and kidney
      was diagnosed in a 4-year-old Neapolitan mastiff. PROCEDURE: The dog presented
      with acute glaucoma of the left eye. Peripheral corneal vascularization and
      severe corneal edema obscured examination of deeper structures. Because of
      concurrent progressive neurologic signs the dog was euthanized and a postmortem
      examination was performed. The eyes, brain and samples from the lung, heart,
      liver and kidneys were fixed in 4% neutral buffered formalin and embedded in
      paraffin wax. Sections were examined by light microscopy including histochemical
      and immunohistochemical staining. RESULTS: The ocular tumor originated from the
      ciliary body and was composed of small islets and cords of poorly differentiated,
      oval to polyhedral cells surrounded by abundant ground substance. Areas with
      chondroid differentiation were observed. Rosettes were not found. Metastases with
      the same morphology were present in the brain and in one kidney. CONCLUSION: An
      intraocular malignant teratoid medulloepithelioma with metastases to the brain
      and kidney is presented.

PMID- 15511283
TI  - B-cell conjunctival lymphoma in a cat.
AB  - A bilateral conjunctival neoplasm was surgically removed from a 13-year-old
      Domestic Short-haired female cat and examined by histopathology. The neoplasm was
      infiltrative, nonencapsulated and composed of large sheets of densely packed,
      round to polygonal cells. Neoplastic cells were variably sized with scant to
      modest amounts of cytoplasm and oval to round nuclei. On immunohistochemistry the
      neoplastic cells stained positively for BLA.36 and negative for CD-3 antibodies.
      On the basis of histopathology and immunohistochemical findings, a diagnosis of
      conjunctival B-cell lymphoma was made. This is the first case with
      immunohistochemical characterization of conjunctival lymphoma in a cat.

PMID- 15511284
TI  - Three cases of prolapse of the nictitans gland in cats.
AB  - We report three cases of adult cats showing a prolapse of the gland of the third
      eyelid. Three different breeds were affected: Burmese, Persian and Domestic Short
      haired. In all cases, the disorder occurred spontaneously, without any other
      ocular sign. Surgical replacement of the gland was performed using the Morgan
      pocket technique. Good esthetic results were obtained, and no recurrence
      occurred.

PMID- 15511285
TI  - Pigmented squamous cell carcinoma of the conjunctiva of a horse.
AB  - Abstract A heavily pigmented tumor was removed from the lateral, perilimbal,
      bulbar conjunctiva of a bay Thoroughbred horse. Excision was incomplete and the
      base of the tumor was lasered on the assumption that the tumor was a melanoma. No
      other ophthalmic lesions were seen. Histology showed the mass to be a pigmented
      squamous cell carcinoma (SCC). The prognosis and recommended treatment protocols
      are different for SCC and melanoma. This is, to the best of our knowledge, the
      first report of an ocular, pigmented SCC in the veterinary literature.

PMID- 15511288
TI  - Neural stem cells express melatonin receptors and neurotrophic factors:
      colocalization of the MT1 receptor with neuronal and glial markers.
AB  - BACKGROUND: In order to optimize the potential benefits of neural stem cell (NSC)
      transplantation for the treatment of neurodegenerative disorders, it is necessary
      to understand their biological characteristics. Although neurotrophin
      transduction strategies are promising, alternative approaches such as the
      modulation of intrinsic neurotrophin expression by NSCs, could also be
      beneficial. Therefore, utilizing the C17.2 neural stem cell line, we have
      examined the expression of selected neurotrophic factors under different in vitro
      conditions. In view of recent evidence suggesting a role for the pineal hormone
      melatonin in vertebrate development, it was also of interest to determine whether
      its G protein-coupled MT1 and MT2 receptors are expressed in NSCs. RESULTS: RT
      PCR analysis revealed robust expression of glial cell-line derived neurotrophic
      factor (GDNF), brain-derived neurotrophic factor (BDNF) and nerve growth factor
      (NGF) in undifferentiated cells maintained for two days in culture. After one
      week, differentiating cells continued to exhibit high expression of BDNF and NGF,
      but GDNF expression was lower or absent, depending on the culture conditions
      utilized. Melatonin MT1 receptor mRNA was detected in NSCs maintained for two
      days in culture, but the MT2 receptor was not seen. An immature MT1 receptor of
      about 30 kDa was detected by western blotting in NSCs cultured for two days,
      whereas a mature receptor of about 40 - 45 kDa was present in cells maintained
      for longer periods. Immunocytochemical studies demonstrated that the MT1 receptor
      is expressed in both neural (beta-tubulin III positive) and glial (GFAP positive)
      progenitor cells. An examination of the effects of melatonin on neurotrophin
      expression revealed that low physiological concentrations of this hormone caused
      a significant induction of GDNF mRNA expression in NSCs following treatment for
      24 hours. CONCLUSIONS: The phenotypic characteristics of C17.2 cells suggest that
      they are a heterogeneous population of NSCs including both neural and glial
      progenitors, as observed under the cell culture conditions used in this study.
      These NSCs have an intrinsic ability to express neurotrophic factors, with an
      apparent suppression of GDNF expression after several days in culture. The
      detection of melatonin receptors in neural stem/progenitor cells suggests
      involvement of this pleiotropic hormone in mammalian neurodevelopment. Moreover,
      the ability of melatonin to induce GDNF expression in C17.2 cells supports a
      functional role for the MT1 receptor expressed in these NSCs. In view of the
      potency of GDNF in promoting the survival of dopaminergic neurons, these novel
      findings have implications for the utilization of melatonin in neuroprotective
      strategies, especially in Parkinson's disease.

PMID- 15511289
TI  - Statistical design considerations for pilot studies transitioning therapies from
      the bench to the bedside.
AB  - Pilot studies are often used to transition therapies developed using animal
      models to a clinical setting. Frequently, the focus of such trials is on
      estimating the safety in terms of the occurrence of certain adverse events. With
      relatively small sample sizes, the probability of observing even relatively
      common events is low; however, inference on the true underlying event rate is
      still necessary even when no events of interest are observed. The exact upper
      limit to the event rate is derived and illustrated graphically. In addition, the
      simple algebraic expression for the confidence bound is seen to be useful in the
      context of planning studies.

PMID- 15511290
TI  - Oligo kernels for datamining on biological sequences: a case study on prokaryotic
      translation initiation sites.
AB  - BACKGROUND: Kernel-based learning algorithms are among the most advanced machine
      learning methods and have been successfully applied to a variety of sequence
      classification tasks within the field of bioinformatics. Conventional kernels
      utilized so far do not provide an easy interpretation of the learnt
      representations in terms of positional and compositional variability of the
      underlying biological signals. RESULTS: We propose a kernel-based approach to
      datamining on biological sequences. With our method it is possible to model and
      analyze positional variability of oligomers of any length in a natural way. On
      one hand this is achieved by mapping the sequences to an intuitive but high
      dimensional feature space, well-suited for interpretation of the learnt models.
      On the other hand, by means of the kernel trick we can provide a general learning
      algorithm for that high-dimensional representation because all required
      statistics can be computed without performing an explicit feature space mapping
      of the sequences. By introducing a kernel parameter that controls the degree of
      position-dependency, our feature space representation can be tailored to the
      characteristics of the biological problem at hand. A regularized learning scheme
      enables application even to biological problems for which only small sets of
      example sequences are available. Our approach includes a visualization method for
      transparent representation of characteristic sequence features. Thereby
      importance of features can be measured in terms of discriminative strength with
      respect to classification of the underlying sequences. To demonstrate and
      validate our concept on a biochemically well-defined case, we analyze E. coli
      translation initiation sites in order to show that we can find biologically
      relevant signals. For that case, our results clearly show that the Shine-Dalgarno
      sequence is the most important signal upstream a start codon. The variability in
      position and composition we found for that signal is in accordance with previous
      biological knowledge. We also find evidence for signals downstream of the start
      codon, previously introduced as transcriptional enhancers. These signals are
      mainly characterized by occurrences of adenine in a region of about 4 nucleotides
      next to the start codon. CONCLUSIONS: We showed that the oligo kernel can provide
      a valuable tool for the analysis of relevant signals in biological sequences. In
      the case of translation initiation sites we could clearly deduce the most
      discriminative motifs and their positional variation from example sequences.
      Attractive features of our approach are its flexibility with respect to oligomer
      length and position conservation. By means of these two parameters oligo kernels
      can easily be adapted to different biological problems.

PMID- 15511291
TI  - Adaptive evolution of transcription factor binding sites.
AB  - BACKGROUND: The regulation of a gene depends on the binding of transcription
      factors to specific sites located in the regulatory region of the gene. The
      generation of these binding sites and of cooperativity between them are essential
      building blocks in the evolution of complex regulatory networks. We study a
      theoretical model for the sequence evolution of binding sites by point mutations.
      The approach is based on biophysical models for the binding of transcription
      factors to DNA. Hence we derive empirically grounded fitness landscapes, which
      enter a population genetics model including mutations, genetic drift, and
      selection. RESULTS: We show that the selection for factor binding generically
      leads to specific correlations between nucleotide frequencies at different
      positions of a binding site. We demonstrate the possibility of rapid adaptive
      evolution generating a new binding site for a given transcription factor by point
      mutations. The evolutionary time required is estimated in terms of the neutral
      (background) mutation rate, the selection coefficient, and the effective
      population size. CONCLUSIONS: The efficiency of binding site formation is seen to
      depend on two joint conditions: the binding site motif must be short enough and
      the promoter region must be long enough. These constraints on promoter
      architecture are indeed seen in eukaryotic systems. Furthermore, we analyse the
      adaptive evolution of genetic switches and of signal integration through binding
      cooperativity between different sites. Experimental tests of this picture
      involving the statistics of polymorphisms and phylogenies of sites are discussed.

PMID- 15511292
TI  - PhyME: a probabilistic algorithm for finding motifs in sets of orthologous
      sequences.
AB  - BACKGROUND: This paper addresses the problem of discovering transcription factor
      binding sites in heterogeneous sequence data, which includes regulatory sequences
      of one or more genes, as well as their orthologs in other species. RESULTS: We
      propose an algorithm that integrates two important aspects of a motif's
      significance - overrepresentation and cross-species conservation - into one
      probabilistic score. The algorithm allows the input orthologous sequences to be
      related by any user-specified phylogenetic tree. It is based on the Expectation
      Maximization technique, and scales well with the number of species and the length
      of input sequences. We evaluate the algorithm on synthetic data, and also present
      results for data sets from yeast, fly, and human. CONCLUSIONS: The results
      demonstrate that the new approach improves motif discovery by exploiting multiple
      species information.

PMID- 15511293
TI  - Seroprevalence of simian immunodeficiency virus in wild and captive born Sykes'
      monkeys (Cercopithecus mitis) in Kenya.
AB  - BACKGROUND: The Sykes' monkey and related forms (Cercopithecus mitis) make up an
      abundant, widespread and morphologically diverse species complex in eastern
      Africa that naturally harbors a distinct simian immunodeficiency virus (SIVsyk).
      We carried out a retrospective serological survey of SIV infection from both wild
      and captive Sykes' monkeys from Kenya. We compared two commercially available,
      cross-reactive ELISA tests using HIV antigens with a novel SIVsyk antigen
      specific Western blot assay and analyzed the data by origin, subspecies, age and
      sex. RESULTS: The SIVsyk antigen-specific Western blot assay detected more serum
      samples as positive than either of the cross-reactive ELISA assays. Using this
      assay, we found that seroprevalence is higher than previously reported, but
      extremely variable in wild populations (from 0.0 to 90.9%). Females were infected
      more often than males in both wild and captive populations. Seropositive infants
      were common. However, no seropositive juveniles were identified. CONCLUSION: We
      have developed a specific and sensitive Western blot assay for anti-SIVsyk
      antibody detection. Sykes' monkeys are commonly infected with SIVsyk, but with
      extremely variable prevalence in the wild. Higher infection prevalence in females
      suggests predominantly sexual transmission. High infection prevalence in infants,
      but none in juveniles, suggests maternal antibodies, but little or no vertical
      transmission.

PMID- 15511295
TI  - Grouping of tooth surfaces by susceptibility to caries: a study in 5-16 year-old
      children.
AB  - BACKGROUND: The decline in caries has slowed and this may be indicative of
      variation in the susceptibility of differing teeth to caries. This study tests
      the hypothesis that in children, there are groups of tooth sites that exhibit
      differences in caries susceptibility. METHODS: Probit analysis of caries data
      collected from a 4-year longitudinal study of 20,000 schoolchildren aged between
      5 and 16 years in 10 differing locations in the United States. RESULTS: The
      development of dental caries within the mouth followed a fixed hierarchy
      indicating that tooth surfaces show variation in caries susceptibility. Certain
      teeth and tooth sites have similar susceptibilities and can be grouped, the sizes
      of the groups vary. The most susceptible group consists of six tooth surfaces:
      the buccal pits and occlusal fissured surfaces of the first molar teeth. The
      second group consisted of 12 sites on the second molar and premolar teeth. The
      group formed by the least susceptible sites included the largest number of tooth
      surfaces and consists of the majority of the lower anterior teeth and canines.
      CONCLUSION: Variation in the caries susceptibility of tooth surfaces exists.
      Surfaces can be grouped according to caries susceptibility. An effect that
      reduces the cariogenic challenge of one of the sites within a group is likely to
      affect all the other sites within the particular group.

PMID- 15511294
TI  - Incremental genetic K-means algorithm and its application in gene expression data
      analysis.
AB  - BACKGROUND: In recent years, clustering algorithms have been effectively applied
      in molecular biology for gene expression data analysis. With the help of
      clustering algorithms such as K-means, hierarchical clustering, SOM, etc, genes
      are partitioned into groups based on the similarity between their expression
      profiles. In this way, functionally related genes are identified. As the amount
      of laboratory data in molecular biology grows exponentially each year due to
      advanced technologies such as Microarray, new efficient and effective methods for
      clustering must be developed to process this growing amount of biological data.
      RESULTS: In this paper, we propose a new clustering algorithm, Incremental
      Genetic K-means Algorithm (IGKA). IGKA is an extension to our previously proposed
      clustering algorithm, the Fast Genetic K-means Algorithm (FGKA). IGKA outperforms
      FGKA when the mutation probability is small. The main idea of IGKA is to
      calculate the objective value Total Within-Cluster Variation (TWCV) and to
      cluster centroids incrementally whenever the mutation probability is small. IGKA
      inherits the salient feature of FGKA of always converging to the global optimum.
      C program is freely available at
      http://database.cs.wayne.edu/proj/FGKA/index.htm. CONCLUSIONS: Our experiments
      indicate that, while the IGKA algorithm has a convergence pattern similar to
      FGKA, it has a better time performance when the mutation probability decreases to
      some point. Finally, we used IGKA to cluster a yeast dataset and found that it
      increased the enrichment of genes of similar function within the cluster.

PMID- 15511296
TI  - SS-Wrapper: a package of wrapper applications for similarity searches on Linux
      clusters.
AB  - BACKGROUND: Large-scale sequence comparison is a powerful tool for biological
      inference in modern molecular biology. Comparing new sequences to those in
      annotated databases is a useful source of functional and structural information
      about these sequences. Using software such as the basic local alignment search
      tool (BLAST) or HMMPFAM to identify statistically significant matches between
      newly sequenced segments of genetic material and those in databases is an
      important task for most molecular biologists. Searching algorithms are
      intrinsically slow and data-intensive, especially in light of the rapid growth of
      biological sequence databases due to the emergence of high throughput DNA
      sequencing techniques. Thus, traditional bioinformatics tools are impractical on
      PCs and even on dedicated UNIX servers. To take advantage of larger databases and
      more reliable methods, high performance computation becomes necessary. RESULTS:
      We describe the implementation of SS-Wrapper (Similarity Search Wrapper), a
      package of wrapper applications that can parallelize similarity search
      applications on a Linux cluster. Our wrapper utilizes a query segmentation-search
      (QS-search) approach to parallelize sequence database search applications. It
      takes into consideration load balancing between each node on the cluster to
      maximize resource usage. QS-search is designed to wrap many different search
      tools, such as BLAST and HMMPFAM using the same interface. This implementation
      does not alter the original program, so newly obtained programs and program
      updates should be accommodated easily. Benchmark experiments using QS-search to
      optimize BLAST and HMMPFAM showed that QS-search accelerated the performance of
      these programs almost linearly in proportion to the number of CPUs used. We have
      also implemented a wrapper that utilizes a database segmentation approach (DS
      BLAST) that provides a complementary solution for BLAST searches when the
      database is too large to fit into the memory of a single node. CONCLUSIONS: Used
      together, QS-search and DS-BLAST provide a flexible solution to adapt sequential
      similarity searching applications in high performance computing environments.
      Their ease of use and their ability to wrap a variety of database search programs
      provide an analytical architecture to assist both the seasoned bioinformaticist
      and the wet-bench biologist.

PMID- 15511297
TI  - Are the effects of nicotinic acid on insulin resistance precipitated by abnormal
      phosphorous metabolism?
AB  - Nicotinic acid is a unique cholesterol modifying agent that exerts favorable
      effects on all cholesterol parameters. It holds promise as one of the main
      pharmacological agents to treat mixed dyslipidemia in metabolic syndrome and
      diabetic patients. The use of nicotinic acid has always been haunted with
      concerns that it might worsen insulin resistance and complicate diabetes
      management. We will discuss the interaction between phosphorous metabolism and
      carbohydrate metabolism and the possibility that worsening of insulin resistance
      could be related to a drug induced alteration in phosphorous metabolism, and the
      implications of that in medical management of diabetes and metabolic syndrome
      patients with mixed dyslipidemia.

PMID- 15511298
TI  - d-matrix - database exploration, visualization and analysis.
AB  - BACKGROUND: Motivated by a biomedical database set up by our group, we aimed to
      develop a generic database front-end with embedded knowledge discovery and
      analysis features. A major focus was the human-oriented representation of the
      data and the enabling of a closed circle of data query, exploration,
      visualization and analysis. RESULTS: We introduce a non-task-specific database
      front-end with a new visualization strategy and built-in analysis features, so
      called d-matrix. d-matrix is web-based and compatible with a broad range of
      database management systems. The graphical outcome consists of boxes whose colors
      show the quality of the underlying information and, as the name suggests, they
      are arranged in matrices. The granularity of the data display allows consequent
      drill-down. Furthermore, d-matrix offers context-sensitive categorization,
      hierarchical sorting and statistical analysis. CONCLUSIONS: d-matrix enables data
      mining, with a high level of interactivity between humans and computer as a
      primary factor. We believe that the presented strategy can be very effective in
      general and especially useful for the integration of distinct data types such as
      phenotypical and molecular data.

PMID- 15511300
TI  - Gastro-enteritis outbreak among Nordic patients with psoriasis in a health centre
      in Gran Canaria, Spain: a cohort study.
AB  - BACKGROUND: Between November 2 and 10, 2002 several patients with psoriasis and
      personnel staying in the health centre in Gran Canaria, Spain fell ill with
      diarrhoea, vomiting or both. Patient original came from Norway, Sweden and
      Finland. The patient group was scheduled to stay until 8 November. A new group of
      patients were due to arrive from 7 November. METHODS: A retrospective cohort
      study was conducted to assess the extent of the outbreak, to identify the source
      and mode of transmission and to prevent similar problems in the following group.
      RESULTS: Altogether 41% (48/116) of persons staying at the centre fell ill.
      Norovirus infection was suspected based on clinical presentations and the fact
      that no bacteria were identified. Kaplan criteria were met. Five persons in this
      outbreak were hospitalised and the mean duration of diarrhoea was 3 days. The
      consequences of the illness were more severe compared to many other norovirus
      outbreaks, possibly because many of the cases suffered from chronic diseases and
      were treated with drugs reported to affect the immunity (methotrexate or
      steroids). During the two first days of the outbreak, the attack rate was higher
      in residents who had consumed dried fruit (adjusted RR = 3.1; 95% CI: 1.4-7.1)
      and strawberry jam (adjusted RR = 1.9; 95% CI: 0.9-4.1) than those who did not.
      In the following days, no association was found. The investigation suggests two
      modes of transmission: a common source for those who fell ill during the two
      first days of the outbreak and thereafter mainly person to person transmission.
      This is supported by a lower risk associated with the two food items at the end
      of the outbreak. CONCLUSIONS: We believe that the food items were contaminated by
      foodhandlers who reported sick before the outbreak started. Control measures were
      successfully implemented; food buffets were banned, strict hygiene measures were
      implemented and sick personnel stayed at home >48 hours after last symptoms.

PMID- 15511299
TI  - Cross-species hybridisation of human and bovine orthologous genes on high density
      cDNA microarrays.
AB  - BACKGROUND: Cross-species gene-expression comparison is a powerful tool for the
      discovery of evolutionarily conserved mechanisms and pathways of expression
      control. The usefulness of cDNA microarrays in this context is that broad areas
      of homology are compared and hybridization probes are sufficiently large that
      small inter-species differences in nucleotide sequence would not affect the
      analytical results. This comparative genomics approach would allow a common set
      of genes within a specific developmental, metabolic, or disease-related gene
      pathway to be evaluated in experimental models of human diseases. The objective
      of this study was to investigate the feasibility and reproducibility of cross
      species analysis employing a human cDNA microarray as probe. RESULTS: As a proof
      of principle, total RNA derived from human and bovine fetal brains was used as a
      source of labelled targets for hybridisation onto a human cDNA microarray
      composed of 349 characterised genes. Each gene was spotted 20 times representing
      6,980 data points thus enabling highly reproducible spot quantification.
      Employing high stringency hybridisation and washing conditions, followed by data
      analysis, revealed slight differences in the expression levels and
      reproducibility of the signals between the two species. We also assigned each of
      the genes into three expression level categories- i.e. high, medium and low. The
      correlation co-efficient of cross hybridisation between the orthologous genes was
      0.94. Verification of the array data by semi-quantitative RT-PCR using common
      primer sequences enabled co-amplification of both human and bovine transcripts.
      Finally, we were able to assign gene names to previously uncharacterised bovine
      ESTs. CONCLUSIONS: Results of our study demonstrate the harnessing and
      utilisation power of comparative genomics and prove the feasibility of using
      human microarrays to facilitate the identification of co-expressed orthologous
      genes in common tissues derived from different species.

PMID- 15511301
TI  - Comparative study of matrix metalloproteinase expression between African American
      and Caucasian Women.
AB  - To date there are 26 human matrix metalloproteinases (MMPs) which are classified
      according to their substrate specificity and structural similarities. The four
      major subgroups of MMPs are gelatinases, interstitial collagenases, stromelysins,
      and membrane-type matrix metalloproteinases (MT-MMPs). This study investigates
      the expression of 26 MMPs, which have been shown to play a role in cancer
      metastasis. Breast tissues and cell lines derived from African American patients
      and Caucasian patients were assayed to demonstrate alterations in the
      transcription of genes primarily responsible for degrading the extracellular
      matrix (ECM). The expression levels of the extracellular matrix and adhesion
      molecules were analyzed using the gene array technology. Steady state levels of
      mRNAs were validated by RT-PCR analysis. Total RNA was isolated from tissue and
      cell lines and used in the RT-PCR assays. From this data, differential expression
      of MMPs between 6 breast cancer cell lines and 2 non-cancer breast cell lines was
      demonstrated. We have performed an in vitro comparison of MMP expression and
      established differences in 12 MMPs (3, 7, 8, 9, 11-15, 23B, 26, and 28)
      expression between African American and Caucasian breast cell lines. Thus,
      evidence indicates that altered expression of MMPs may play a role in the
      aggressive phenotype seen in African American women.

PMID- 15511302
TI  - Validity of the Clock Drawing Test in predicting reports of driving problems in
      the elderly.
AB  - BACKGROUND: This study examined the use of the Folstein Mini Mental Status Exam
      (MMSE) and the Clock Drawing Test (CDT) in predicting retrospective reports of
      driving problems among the elderly. The utility of existing scoring systems for
      the CDT was also examined. METHODS: Archival chart records of 325 patients of a
      geriatric outpatient clinic were reviewed, of which 162 had CDT results
      (including original clock drawings). T-test, correlation, and regression
      procedures were used to analyze the data. RESULTS: Both CDT and MMSE scores were
      significantly worse among non-drivers than individuals who were currently or
      recently driving. Among current or recent drivers, scores on both instruments
      correlated significantly with the total number of reported accidents or near
      misses, although the magnitude of the respective correlations was small. Only
      MMSE scores, however, significantly predicted whether or not any accidents or
      near misses were reported at all. Neither MMSE nor CDT scores predicted unique
      variance in the regressions. CONCLUSIONS: The overall results suggest that both
      the MMSE and CDT have limited utility as potential indicators of driving problems
      in the elderly. The demonstrated predictive power for these instruments appears
      to be redundant, such that both appear to assess general cognitive function
      versus more specific abilities. Furthermore, the lack of robust prediction
      suggests that neither are sufficient to serve as stand-alone instruments on which
      to solely base decisions of driving capacity. Rather, individuals who evidence
      impairment should be provided a more thorough and comprehensive assessment than
      can be obtained through screening tools.

PMID- 15511303
TI  - Statistical inference and Aristotle's Rhetoric.
AB  - Formal logic operates in a closed system where all the information relevant to
      any conclusion is present, whereas this is not the case when one reasons about
      events and states of the world. Pollard and Richardson drew attention to the fact
      that the reasoning behind statistical tests does not lead to logically
      justifiable conclusions. In this paper statistical inferences are defended not by
      logic but by the standards of everyday reasoning. Aristotle invented formal
      logic, but argued that people mostly get at the truth with the aid of enthymemes-
      incomplete syllogisms which include arguing from examples, analogies and signs.
      It is proposed that statistical tests work in the same way--in that they are
      based on examples, invoke the analogy of a model and use the size of the effect
      under test as a sign that the chance hypothesis is unlikely. Of existing theories
      of statistical inference only a weak version of Fisher's takes this into account.
      Aristotle anticipated Fisher by producing an argument of the form that there were
      too many cases in which an outcome went in a particular direction for that
      direction to be plausibly attributed to chance. We can therefore conclude that
      Aristotle would have approved of statistical inference and there is a good reason
      for calling this form of statistical inference classical.

PMID- 15511304
TI  - A multivariate projection-type analogue of the Wilcoxon-Mann-Whitney test.
AB  - The problem of comparing two independent groups based on mulitivariate data is
      considered. Many such methods have been proposed, but it is difficult to gain a
      perspective on the extent to which the groups differ. The basic strategy here is
      to determine a robust measure of location for each group, project the data onto
      the line connecting these measures of location, and then compare the groups based
      on the ordering of the projected points. In the univariate case the method uses
      the same measure of effect size employed by the Wilcoxon-Mann-Whitney test. Under
      general conditions, the projected points are dependent, causing difficulties when
      testing hypotheses. Two methods are found to be effective when trying to avoid
      Type I error probabilities above the nominal level. The relative merits of the
      two methods are discussed. The projected data provide not only a useful
      (numerical) measure of effect size, but also a graphical indication of the extent
      to which groups differ.

PMID- 15511305
TI  - Comparing measures of the 'typical' score across treatment groups.
AB  - Researchers can adopt one of many different measures of central tendency to
      examine the effect of a treatment variable across groups. These include least
      squares means, trimmed means, M-estimators and medians. In addition, some methods
      begin with a preliminary test to determine the shapes of distributions before
      adopting a particular estimator of the typical score. We compared a number of
      recently developed adaptive robust methods with respect to their ability to
      control Type I error and their sensitivity to detect differences between the
      groups when data were non-normal and heterogeneous, and the design was
      unbalanced. In particular, two new approaches to comparing the typical score
      across treatment groups, due to Babu, Padmanabhan, and Puri, were compared to two
      new methods presented by Wilcox and by Keselman, Wilcox, Othman, and Fradette.
      The procedures examined generally resulted in good Type I error control and
      therefore, on the basis of this critetion, it would be difficult to recommend one
      method over the other. However, the power results clearly favour one of the
      methods presented by Wilcox and Keselman; indeed, in the vast majority of the
      cases investigated, this most favoured approach had substantially larger power
      values than the other procedures, particularly when there were more than two
      treatment groups.

PMID- 15511306
TI  - On the correlation of a naturally and an artificially dichotomized variable.
AB  - A method is suggested for estimating the correlation of a naturally (X) and an
      artificially (Y) dichotomized variable. It is assumed that a normal random
      variable (L) underlies the artificially dichotomized variable. The proposed
      correlation coefficient recovers the product moment correlation coefficient
      between X and L from a fourfold table of X and Y. The suggested correlation
      coefficient nu is contrasted with the phi correlation and the biserial eta. The
      biserial eta was proposed by Karl Pearson and is conceptually related to the new
      correlation coefficient. However, in addition, Pearson's biserial eta invokes the
      assumption that the marginal distribution of L is normal, which contradicts its
      basic assumptions and thus does not recover the true correlation of L and X.
      Finally, an approximation is provided to simplify the calculation of nu and its
      standard error.

PMID- 15511307
TI  - Examining time-invariance in reliability in multi-wave, multi-indicator models: a
      covariance structure analysis approach accounting for indicator specificity.
AB  - A covariance structure analysis method for testing time-invariance in reliability
      in multiwave, multiple-indicator models in outlined. The approach accounts for
      observed variable specificity and permits, in addition, estimation of reliability
      in terms of 'pure' measurement error variance. The proposed procedure is
      developed within a confirmatory factor analysis framework and illustrated with
      data from a cognitive intervention study.

PMID- 15511308
TI  - Some results on extensions and modifications of the Theil-Sen regression
      estimator.
AB  - Many robust regression estimators have been proposed that have a high, finite
      sample breakdown point, roughly meaning that a large proportion of points must be
      altered to drive the value of an estimator to infinity. But despite this, many of
      them can be inordinately influenced by two properly placed outliers. With one
      predictor, an estimator that appears to correct this problem to a fair degree,
      and simultaneously maintain good efficiency when standard assumptions are met,
      consists of checking for outliers using a projection-type method, removing any
      that are found, and applying the Theil-Sen estimator to the data that remain.
      When dealing with multiple predictors, there are two generalizations of the Theil
      Sen estimator that might be used, but nothing is known about how their small
      sample properties compare. Also, there are no results on testing the hypothesis
      of zero slopes, and there is no information about the effect on efficiency when
      outliers are removed. In terms of hypothesis testing, using the more obvious
      percentile bootstrap method in conjunction with a slight modification of
      Mahalanobis distance was found to avoid Type I error probabilities above the
      nominal level, but in some situations the actual Type I error probabilities can
      be substantially smaller than intended when the sample size is small. An
      alternative method is found to be more satisfactory.

PMID- 15511309
TI  - Bradley-Terry-Luce models to incorporate within-pair order effects:
      representation and uniqueness theorems.
AB  - The paper presents different representation theorems for the Bradley-Terry-Luce
      (BTL) models of Beaver and Gokhale and of Davidson and Beaver. In particular,
      algorithms that can be used in constructing BTL scales are provided. The
      uniqueness theorems show that the Davidson-Beaver model should be preferred to
      the Beaver-Gokhale model since the multiplicative order effect parameter is
      uniquely determined whereas the additive effect parameter is merely a ratio
      scale. Finally, a relationship to the simple BTL model is established. Let p(a,
      b) denote the probability that a is chosen when (a, b) is presented in a fixed
      order. Then the probabilities p(a, b) satisfy the Beaver-Gokhale model if and
      only if the balanced probabilities pb(a, b) := (1/2)(p(a, b) + 1-p(b, a)) satisfy
      the simple BTL model.

PMID- 15511310
TI  - A generalized estimating equations approach to mixed-effects ordinal probit
      models.
AB  - Clustered ordinal responses, which are commonplace in behavioural and educational
      research, are often analysed using mixed-effects ordinal probit models.
      Likelihood-based inference for these models can be computationally burdensome,
      and may compromise the consistency of estimators if the model is misspecified. We
      propose an alternative inferential approach based on generalized estimating
      equations. We show that systems of estimating equations can be specified for
      mixed-effects ordinal probit models that avoid the potentially heavy
      computational demands of maximum likelihood estimation, and can also provide
      inferences that are robust with respect to some forms of model misspecification-
      particularly serial effects in longitudinal data.

PMID- 15511311
TI  - Convergence in mean square of factor predictors.
AB  - Sufficient conditions for mean square convergence of factor predictors in common
      factor analysis are given by Guttman, by Williams, and by Schneeweiss and Mathes.
      These conditions do not hold for confirmatory factor analysis or when an error
      variance equals zero (Heywood cases). Two sufficient conditions are given for the
      three basic factor predictors and a predictor from rotated principal components
      analysis to converge to the factors of the model for confirmatory factor
      analysis, including Heywood cases. For certain model specifications the
      conditions are necessary. The conditions are sufficient for the existence of a
      unique true factor. A geometric interpretation is given for factor indeterminacy
      and mean square convergence of best linear factor prediction.

PMID- 15511312
TI  - The use of item parcels in structural equation modelling: non-normal data and
      small sample sizes.
AB  - Maximum likelihood estimation in confirmatory factor analysis requires large
      sample sizes, normally distributed item responses, and reliable indicators of
      each latent construct, but these ideals are rarely met. We examine alternative
      strategies for dealing with non-normal data, particularly when the sample size is
      small. In two simulation studies, we systematically varied: the degree of non
      normality; the sample size from 50 to 1000; the way of indicator formation,
      comparing items versus parcels; the parcelling strategy, evaluating uniformly
      positively skews and kurtosis parcels versus those with counterbalancing skews
      and kurtosis; and the estimation procedure, contrasting maximum likelihood and
      asymptotically distribution-free methods. We evaluated the convergence behaviour
      of solutions, as well as the systematic bias and variability of parameter
      estimates, and goodness of fit.

PMID- 15511313
TI  - Asymptotic biases of the unrotated/rotated solutions in principal component
      analysis.
AB  - Asymptotic biases of the parameter estimates in principal component analysis with
      substantial misspecification are derived. The solutions for unstandardized and
      standardized observed variables are considered with and without orthogonal and
      oblique rotations. The distribution of observed variables can be non-normal as
      long as the finite fourth-order moments of the observed variables exist. When
      multivariate normality holds for the observed variables, substantial reduction of
      the amount of computation can be achieved. Numerical examples with simulations
      are given, with some discussion on the tendency of the biases to reduce the
      absolute values of parameter estimates.

PMID- 15511317
TI  - Patient and public involvement.

PMID- 15511318
TI  - Health services research, policy and practice in Australia and New Zealand: a
      coming of age.

PMID- 15511319
TI  - Health services research in Australia: an investigation of its current status.
AB  - OBJECTIVES: The objectives of this audit were to document the current status of
      health services research (HSR) in Australia in terms of inputs and outputs.
      Inputs were defined as the number of organised centres or groups undertaking HSR,
      the extent to which HSR was being developed and the funding available for HSR.
      Outputs were measured as the number of peer-reviewed papers. METHODS: Centres or
      groups were identified via the membership of the HSRAANZ and a web-based search.
      Information from annual reports and/or other published sources was used to
      determine the extent of capacity building and available funding. The tables of
      contents of 21 journals published over a 10-year period were searched for
      articles reporting Australian HSR. RESULTS: Eighteen groups were identified that
      undertook HSR as their predominant activity, while twelve were involved in HSR as
      a collaborative activity. No HSR-specific training (in terms of under- or
      postgraduate degrees) was identified, although more than 400 postgraduate
      students were being supervised in the university departments where HSR groups
      were situated. Between 1998 and 2001, more than 13 million Australian dollars was
      awarded for HSR, most of it by the National Health and Medical Research Council
      (NHMRC). Over the past 10 years, 482 articles about Australian health services
      have been published in the peer-reviewed journals audited. CONCLUSIONS: Although
      HSR is widespread in Australia, no specific training appears to be available to
      build capacity. Overall, HSR is not well-funded especially by organisations
      outside the NHMRC or Australian Research Council. Thus, it is not surprising that
      the output of Australian HSR, in terms of peer-reviewed articles, is slight.

PMID- 15511320
TI  - The influence of socio-economic and locational disadvantage on survival after a
      diagnosis of lung or breast cancer in Western Australia.
AB  - OBJECTIVE: The effects of demographic, locational and socio-economic
      disadvantage, and the influence of private health care on five-year mortality
      rates in patients with lung cancer or after breast cancer surgery in Western
      Australia were examined. METHODS: The Western Australian Record Linkage Project
      was used to extract all hospital morbidity, cancer and death records of all
      people with lung or breast cancer in Western Australia from 1982 to 1996.
      Mortality rate ratios after a diagnosis of lung cancer or breast cancer surgery
      were estimated using Cox regression. Two sets of analyses were carried out:
      demographically adjusted from 1982 to 1996; and demographically and disadvantage
      adjusted from 1992 to 1996. RESULTS: Overall, 87.7% of lung cancer and 17.8% of
      breast cancer patients were deceased by five years. Lung and breast cancer
      patients treated in rural hospitals had higher mortality rates (1992-1996:
      relative risk (RR) 1.24, 95% confidence interval (CI) 1.07-1.44, and RR 1.20, 95%
      CI 0.92-1.56, respectively; 1982-1996: RR 1.20, 95% CI 1.11-1.30, and RR 1.19,
      95% CI 1.06-1.33, respectively), whereas location of residence had little effect.
      Lung and breast cancer patients treated in private hospitals had lower mortality
      (1992-1996: RR 0.85, 95% CI 0.76-0.95, and RR 0.90, 95% CI 0.77-1.05,
      respectively; 1982-1996: RR 0.91, 95% CI 0.84-0.97, and RR 0.92, 95% CI 0.85
      0.99, respectively), although insurance status was not a factor. Women with
      breast cancer had significantly worse survival in the more socio-economically
      disadvantaged groups (1992-1996: RR 1.41 to 1.26; 1982-1996: RR 1.45 to 1.29).
      CONCLUSIONS: Survival was poorer in patients treated in the public hospital
      system, but the possession of private health insurance was not predictive of
      better outcomes. People treated in rural hospitals had worse survival, whereas
      location of residence was not an independent factor. Women in more socio
      economically advantaged groups who underwent breast cancer surgery had improved
      survival.

PMID- 15511321
TI  - Comparison of private for-profit with private community-governed not-for-profit
      primary care services in New Zealand.
AB  - OBJECTIVE: To compare the characteristics of patients, their disease patterns,
      and the investigation and referral patterns in private community-governed not-for
      profit and private for-profit primary care practices in New Zealand. METHODS:
      Observational study using a representative survey of visits to general
      practitioners in New Zealand. Practices were categorised according to their
      ownership: private for-profit or private community-governed not-for-profit.
      Patient socio-demographic characteristics, treated prevalence and other
      characteristics of presenting problems, morbidity burden, numbers of
      investigations and referral patterns were compared. RESULTS: Compared with for
      profit practices, community-governed not-for-profit practices served a younger,
      largely non-European population, nearly three-quarters of whom had a means-tested
      benefit card (community services card), 10.5% of whom were not fluent in English,
      and the majority of whom lived in the 20% of areas ranked as the most deprived
      (by the NZDep2001 index of socio-economic deprivation). Patients visiting not-for
      profit practices were diagnosed with more problems, including higher rates of
      asthma, diabetes and skin infections, but lower rates of chest infections. The
      duration of visits was also significantly longer. No differences were observed in
      the average number of laboratory tests ordered. The odds of specialist referral
      were higher in for-profit patients when confounding variables were controlled
      for. CONCLUSIONS: Community-governed not-for-profit practices in New Zealand
      serve a poor, largely non-European population who present with somewhat different
      rates of various problems compared with patients at for-profit practices. The
      study highlights for communities, policy-makers and purchasers the importance of
      community-governed not-for-profit practices in meeting the needs of low-income
      and minority population groups.

PMID- 15511322
TI  - Did the invisible hand rock the cradle? An investigation of children's
      hospitalisations in New Zealand.
AB  - OBJECTIVES: To test the hypothesis that the overall growth in children's
      hospitalisations since the instigation of New Zealand's economic and social
      reforms in 1984 reflects an increase in morbidity caused by socio-economic
      factors such as poverty, unemployment, household overcrowding and the cost of
      primary care. METHODS: All publicly funded hospitalisations amongst children aged
      1-14 years, for the years 1988/89 to 2002/03, were categorised as either
      avoidable or unavoidable based on primary discharge diagnosis. Trends in
      avoidable and unavoidable hospitalisation rates over time and for various
      demographic and socio-economic groups were analysed. RESULTS: Growth in avoidable
      and unavoidable hospitalisations amongst children was similar over the period,
      with unavoidable hospitalisations growing slightly faster. Growth in avoidable
      hospitalisations was greatest for children who live in the least deprived areas
      and lowest for children who live in the most deprived areas. Making primary care
      substantially free for children aged less than six years did not appear to slow
      the growth in avoidable hospitalisations. CONCLUSIONS: Trends in avoidable and
      unavoidable hospitalisations over time are not consistent with the hypothesis
      being tested. The available evidence does not support a link between morbidity
      attributable to socio-economic factors and growth in children's hospitalisations.
      Given the lack of other evidence for deterioration in overall child health, the
      available evidence does not support a link between economic and social reforms in
      New Zealand and a decline in children's health status.

PMID- 15511323
TI  - The social capital:health relationship in two disadvantaged neighbourhoods.
AB  - OBJECTIVES: Research into the social determinants of health inequalities is
      increasingly focusing on macro-level forces affecting individuals and
      communities. The concept of social capital has been at the centre of this
      research as a potential explanatory framework for understanding these
      inequalities. The aim of this study was to identify the components that define
      social capital and its relationship to self-reported health in two neighbourhoods
      known to be disadvantaged in south-western Sydney. METHODS: This study uses data
      from cross-sectional household (door-knock) surveys originally developed as
      evaluation tools for neighbourhood based interventions. Secondary analyses
      including factor analysis and multiple regression analysis were used to provide
      empirical evidence of the components defining social capital and how these, as a
      concept, were associated with self-reported health. RESULTS: The study revealed
      six common social capital components in each sample and an additional component
      in one neighbourhood. These included neighbourhood attachment, support networks,
      feelings of trust and reciprocity, local engagement, personal attachment to the
      area, feelings about safety and proactivity in the social context. The social
      capital model incorporating demographic and socio-economic characteristics
      explained 23.4% of health variance in one neighbourhood, and 19.3% in the other.
      Examining the social capital:health relationship revealed that with the exception
      of feelings of trust and reciprocity, no other social capital component made
      significant contributions to explaining health variance and that macro-level
      factors such as housing conditions and employment opportunities emerged as key
      explanatory factors. CONCLUSION: If interventions are to use social capital as a
      way of addressing health inequalities, these need to look closely at the role of
      trust for improving health outcomes of deprived populations as well as ensuring
      access to resources and infrastructure.

PMID- 15511324
TI  - Indigenous participation in the 'new' New Zealand health structure.
AB  - OBJECTIVES: This paper presents preliminary evaluative findings from research on
      key areas of concern to Maori and forms part of a wider project on the 2001
      health system reforms in New Zealand. The paper reports on the development and
      implementation of the Maori Health Strategy, representation in decision making at
      governance level in District Health Boards, the inclusion of the Treaty of
      Waitangi in legislation and workforce issues. METHODS: Key informant interviews
      with 35 Maori and non-Maori respondents, in addition to data from five case study
      districts, were thematically analysed to gain an understanding of views on the
      health system reforms to date. RESULTS: The development of a Maori Health
      Strategy and the mandatory inclusion of Maori in governance and consultation
      processes have had a positive effect on Maori participation in the public health
      sector. Whereas previously Maori participation was concentrated in health service
      provision, the inclusion of specific provisions in the New Zealand Public Health
      and Disability Act 2000 has resulted in greater Maori inclusion in governance,
      planning and decision-making roles. However, there are concerns over strategy
      implementation, sustainability and workforce development. CONCLUSIONS: Overall,
      the findings at this stage indicate that there is support for the post-2000
      model. Maori and non-Maori alike have identified positive features of the model
      that could go some way towards contributing to improved Maori health. However
      challenges still remain.

PMID- 15511325
TI  - Equity of access to elective surgery: reflections from NZ clinicians.
AB  - OBJECTIVES: To explore factors potentially influencing equitable access to
      elective surgery in New Zealand by describing clinicians' perceptions of equity
      and the factors they consider when prioritising patients for elective surgery.
      METHODS: A qualitative study in selected New Zealand localities. A purposive
      sample of 49 general practitioners, specialists and registrars were interviewed.
      Data were analysed thematically. RESULTS: General practitioners described unequal
      opportunities for patients to access primary and secondary care and, in
      particular, private sector elective surgery. They felt that socio-economically
      disadvantaged patients were less able to advocate for themselves and were more
      vulnerable to being lost to the elective surgical booking system as well as being
      less able to access private care. Both GPs and secondary care clinicians
      described situations where they would personally advocate for individual patients
      to improve their access. Advocacy was related to clinicians' perceptions of the
      'value' that patients would receive from the surgery and patients' needs for
      public sector funding. CONCLUSIONS: The structure of the health system
      contributes to inequities in access to elective care in New Zealand. Subjective
      decision making by clinicians has the potential to advantage or disadvantage
      patients through the weighting clinicians place on socio-demographic factors when
      making rationing decisions. Review of the potential structural barriers to
      equitable access, further public debate and guidance for clinicians on the
      relative importance of socio-demographic factors in deciding access to rationed
      services are required for allocation of services to be fair.

PMID- 15511326
TI  - Variation in specialist fees: evidence from New Zealand insurance claims.
AB  - OBJECTIVES: To examine the parity between specialties in reimbursements for
      surgical procedures in a private, fee-for-service setting and to ascertain
      whether differences exist after accounting for factors suggested by a Resource
      Based Relative Value Scale (RBRVS). METHODS: A routinely updated database
      covering several private insurers (n = 8294 procedures from 1997 to 2002) was
      used to examine differences in overall and hourly reimbursement. Multiple
      regression analysis was used to control for factors that might be responsible for
      differences in payment (location, year, sex of patient and the associated
      anaesthetist fee). The resulting regression residuals were compared between
      specialties. RESULTS: Large differences between specialties in reimbursements
      were found in the overall amount paid. For most specialties, these differences
      were explained by factors such as time for procedure, location, complexity of
      procedure and sex of patients. However, hourly reimbursements for
      ophthalmologists were substantially higher (more than 50% above general surgery
      overall and 72% higher on an hourly basis). Some other smaller differences in
      overall and hourly reimbursement were also found. CONCLUSIONS: These results
      indicate that specialist fees vary significantly but many of the differences are
      explainable by factors incorporated into the RBRVS. However, significant
      variation remains for some specialties, most notably ophthalmology. Explanations
      for the results are discussed, including the possibility that political factors
      may influence the setting of specialist fees. This raises questions concerning
      the fairness of reimbursements and resulting solidarity within the medical
      profession.

PMID- 15511327
TI  - Specialist clinics in remote Australian Aboriginal communities: where rock art
      meets rocket science.
AB  - People in remote Aboriginal communities in the Northern Territory have greater
      morbidity and mortality than other Australians, but face considerable barriers
      when accessing hospital-based specialist services. The Specialist Outreach
      Service, which began in 1997, was a novel policy initiative to improve access by
      providing a regular multidisciplinary visiting specialist services to remote
      communities. It led to two interesting juxtapositions: that of 'state of the art'
      specialist services alongside under-resourced primary care in remote and
      relatively traditional Aboriginal communities; and that of attempts to develop an
      evidence base for the effectiveness of outreach, while meeting the short-term
      evaluative requirements of policy-makers. In this essay, first we describe the
      development of the service in the Northern Territory and its initial process
      evaluation. Through a Cochrane systematic review we then summarise the published
      research on the effectiveness of specialist outreach in improving access to
      tertiary and hospital-based care. Finally we describe the findings of an
      observational population-based study of the use of specialist services and the
      impact of outreach to three remote communities over 11 years. Specialist outreach
      improves access to specialist care and may lessen the demand for both outpatient
      and inpatient hospital care. Specialist outreach is, however, dependent on well
      functioning primary care. According to the way in which outreach is conducted and
      the service is organised, it can either support primary care or it can hinder
      primary care and, as a result, reduce its own effectiveness.

PMID- 15511328
TI  - Pricing of general practice in Australia: some recent proposals to reform
      Medicare.
AB  - In the Australian Medicare system, general practitioners (GPs) are paid on a fee
      for-service basis. A practitioner can choose to bill the government directly
      (termed bulk billing) and receive 85% of a regulated fee as full payment. Bulk
      billed consultations are free to the patient. However, GPs are free to charge
      above the regulated fee. The patient can then claim a rebate from the government
      but only the equivalent of 85% of the regulated Medicare fee. Such copayments for
      GP consultations cannot be covered by private health insurance. In the ten years
      following the introduction of Medicare in 1984, the bulk billing rate for GP
      consultations steadily increased to 84%. Since then the rate has fallen to below
      68%. In April 2003 the Minister for Health announced a reform package under the
      title A Fairer Medicare which aimed, among other things, to increase the
      availability of bulk billing for some patients. A key feature of the proposal
      involved changes to the way that GPs are reimbursed. Following political
      opposition that would have prevented it passing both houses of the federal
      parliament, a revised version, MedicarePlus, was released in November 2003. This
      paper describes the factors influencing a GP's choice to bulk bill and examines
      the two proposals, in this context.

PMID- 15511330
TI  - Monochorionic triplets after single embryo transfer.
AB  - A 40-year-old patient underwent intracytoplasmic sperm injection and assisted
      hatching, and a single embryo was transferred. Ultrasonography demonstrated a
      single gestational sac containing monochorionic tri-amniotic pregnancy. Several
      factors that have been implicated in the aetiology of monozygotic triple
      pregnancies after IVF appear to be present in this case. To avoid multiple
      pregnancies after IVF, it is time to have definite predictive factors for the
      occurrence of monozygotic multiple pregnancies as well as transferring only a
      single embryo.

PMID- 15511332
TI  - A moral case study for discussion: designer babies and tissue typing.
AB  - The morality of designer babies is presented in a new light designed to stimulate
      discussion and responses. The article ends on a query requiring immediate
      answers.

PMID- 15511333
TI  - Evaluation of a pen device for self-administration of recombinant human FSH in
      clomiphene citrate-resistant anovulatory women undergoing ovulation induction.
AB  - This open-label multicentre study evaluated ease of use, safety, and efficacy of
      a pen device for self-administration of recombinant follicle-stimulating hormone
      (rFSH) in 43 subjects undergoing ovulation induction. Follitropin beta was
      administered subcutaneously with the Follistim Pen within 3 days of onset of
      menses. A 75 IU starting dose could be increased by 25 or 50 IU on days 8 and 15
      if no ovarian response was observed. Human chorionic gonadotrophin (HCG; 10,000
      IU) was administered when one follicle > or =18 mm or two to three follicles > or
      =15 mm were observed. Subjects received standardized instruction for the pen
      device and subject comprehension was recorded as subjects practised and prepared
      injections. Ease of use was also evaluated by questionnaire. Forty-four subjects
      enrolled; 43 were treated with rFSH and 41 were treated with HCG. The
      comprehension questionnaire revealed that during the mock injection, 100% of
      subjects properly loaded the cartridge into the pen device, while 95% selected
      the correct dose and 100% self-injected the medication prescribed. During the
      second actual injection, 100% of subjects comprehended these pen-related steps.
      The ease-of-use questionnaire showed that 100% of the subjects rated the overall
      experience of self-administering with the pen as 'very good' to 'good'. Mean
      duration and total amount of follitropin beta were 11.4 +/- 4.2 days and 1070.3
      +/- 580.3 IU respectively. Ovulation rate was 95%. Biochemical and ongoing
      pregnancy rates per attempt were 34.9 and 30.2% respectively. Three subjects
      experienced serious adverse events [asthma; ovarian hyperstimulation syndrome
      (OHSS) and pain; OHSS]. In conclusion, the pen device provides an easy, safe, and
      effective way for women to self-administer follitropin beta during ovarian
      stimulation.

PMID- 15511336
TI  - Ovulation induction in women with polycystic ovary syndrome: randomized trial of
      clomiphene citrate versus low-dose recombinant FSH as first line therapy.
AB  - This single centre randomized controlled trial was undertaken to compare the
      efficacy and safety of clomiphene citrate and low-dose recombinant FSH as first
      line pharmacological therapy for anovulatory infertility associated with
      polycystic ovary syndrome (PCOS). Seventy-six infertile patients with PCOS were
      randomized to receive clomiphene citrate (50-150 mg/day for 5 days) (clomiphene
      citrate group, n = 38) or recombinant human FSH (FSH group, n = 38) in a chronic,
      low-dose, step-up protocol (daily starting dose 75 IU) for up to three
      consecutive cycles. Ovarian response was monitored by transvaginal
      ultrasonography and human chorionic gonadotrophin (HCG) was given to trigger
      ovulation in all cycles with appropriate follicular development. The primary
      outcome measure was cumulative pregnancy after undergoing up to three treatment
      cycles. Secondary outcomes were cycle cancellation rate, ovulation rate per
      cycle, cumulative ovulation rate, pregnancy rate per cycle, incidence of OHSS,
      cumulative live birth rate, and multiple birth rate. One hundred and four
      clomiphene citrate cycles and 91 FSH cycles were evaluable. The relative risk and
      its 95% confidence interval were 1.17 (0.97-1.46) for HCG cycles with ovulation,
      1.78 (0.92-3.54) for the pregnancy rate per woman, and 1.83 (0.79-4.40) for live
      births per woman in favour of FSH. The cumulative pregnancy rate after three
      treatment cycles was 43% with FSH and 24% with clomiphene citrate (P = 0.06). By
      logistic regression analysis, the factors predicting ovulation included female
      age, serum androstenedione and use of FSH. Predictors of pregnancy were duration
      of infertility and use of FSH. This randomized controlled trial suggests that low
      dose recombinant FSH may be an effective alternative to clomiphene citrate in
      first-line treatment for anovulatory PCOS patients. Thus, further studies,
      possibly multi-centre, in order to avoid problems with patient recruitment, are
      warranted to confirm these results.

PMID- 15511338
TI  - Collagen IV-mediated signalling is involved in progenitor Leydig cell
      proliferation.
AB  - In rats, during postnatal Leydig cell development, the progenitor Leydig cells
      (PLC) proliferate actively during days 14-21 of postnatal life. Luteinizing
      hormone (LH) is known to stimulate Leydig cell proliferation and oestradiol
      17beta inhibits this process. In order to identify the molecules involved in
      Leydig cell proliferation, differentially expressed genes in proliferating and
      non-proliferating PLC isolated from vehicle and oestradiol 17beta-treated rats
      respectively, were analysed by differential display reverse transcription
      polymerase chain reaction (DD-RT-PCR). Results revealed that the expression of
      collagen IV alpha4 (Col IV alpha4), a subunit of extracellular matrix (ECM)
      protein collagen IV, was down regulated in PLC isolated from oestradiol 17beta
      treated rats. Studies on stage specific expression of Col IV alpha4 during Leydig
      cell development revealed that this transcript is abundantly expressed at the
      stage where Leydig cell proliferation is maximal and the expression of this
      transcript decreased during differentiation of Leydig cells, which is associated
      with loss of proliferation. These observations suggest that Col IV alpha4 is
      important for PLC proliferation. Stimulation of PLC proliferation in vitro in the
      presence collagen IV provides additional support for the conclusion that collagen
      IV-mediated signalling is involved in PLC proliferation. Further studies revealed
      that active forms of focal adhesion kinase (FAK) and mitogen activated protein
      kinase 1/2 (MAPK 1/2), the intracellular signalling molecules that are known to
      mediate ECM protein signalling are present only in proliferating forms of Leydig
      cells and are absent in non-proliferating Leydig cells. These results suggest
      that collagen IV-mediated signalling is involved in PLC proliferation.

PMID- 15511340
TI  - Efficacy of IVF using frozen donor semen in cases of previously failed DI cycles
      compared with tubal infertility: a cohort study.
AB  - A cohort follow-up study was designed to compare the efficacy of IVF using frozen
      donor semen (IVF-D) following previously failed DI cycles (unexplained female
      infertility) and direct IVF-D treatment because of tubal infertility (control
      group). The cohort comprised 189 couples initiating IVF-D after previously failed
      DI cycles (n = 126) or directly (n = 63). Couples were followed until completion
      (success or drop-out for personal or medical reasons). Live births and drop-out
      were expressed both as rate per cycle and crude cumulative rate. Characteristics
      of IVF-D cycles were similar between the two groups. Moreover, overall outcome
      was also similar in terms of crude cumulative live birth rate (54.0 versus 57.1%
      for failed DI cycles and tubal infertility groups respectively). This is the
      first report on crude cumulative live birth rate based on a cohort follow-up
      study in unexplained previously failed DI cycles and tubal infertility.
      Previously failed DI cycles did not impair the chances of achieving a successful
      pregnancy using IVF-D in this series. Slight oocyte dysfunction, which might
      underlie the failure of DI cycles, might be overcome using IVF-D.

PMID- 15511341
TI  - Impact of oxygen concentration on embryonic development of mouse zygotes.
AB  - The aim of the present study was to examine the effect of culture under 5 and 20%
      oxygen on the development, differentiation and viability of zygotes and in-vivo
      produced embryos at the 2-cell and 8-cell stages of development. First, zygotes
      collected in a common pool were cultured in 20% O2 for 0, 23, 46 and 95 h.
      Zygotes and in-vivo-produced embryos at the 2-cell and 8-cell stages of
      development were then cultured in 5 or 20% O2. The proportion of embryos reaching
      the compaction and blastocyst stages of development did not differ between groups
      regardless of the period of time embryos were cultured in 20% O2 or the stage at
      beginning of culture. Duration of culture under 20% O2 had a significant effect
      on total number of blastocyst cells. A stage-specific effect was observed on
      total and trophectoderm cell numbers in blastocysts resulting from the culture of
      zygotes and in-vivo-produced embryos under 20% O2. ICM and percent ICM
      development was significantly decreased by culture in 20% O2 at all stages
      examined. Oxygen concentration had no effect on implantation rate and fetal
      weights upon embryo transfer. However, transfer of zygotes grown to the
      blastocyst stage in 20% O2 resulted in a dramatic decrease in fetal development
      per blastocyst and fetal development per implantation. These results demonstrate
      that culture of F1 mouse zygotes in 20% O2 compromises the developmental
      potential of resultant blastocysts, which appear to be normal on morphological
      assessment.

PMID- 15511342
TI  - Mitochondrial DNA turnover occurs during preimplantation development and can be
      modulated by environmental factors.
AB  - There is increasing evidence in humans that abnormal mitochondrial DNA (mtDNA) is
      associated with common degenerative disorders of the twenty-first century. MtDNA
      is exclusively female in origin and abnormalities in mtDNA can either be
      inherited, or generated de novo by adverse environmental factors that disturb
      mitochondrial DNA synthesis or destabilize mtDNA. The preimplantation period of
      development in mammals was thought to be relatively immune from environmentally
      induced changes to mtDNA, since no replication of mtDNA was thought to occur at
      this stage. This study demonstrates that there is a very short period of mtDNA
      synthesis immediately after fertilization, which can be affected by environmental
      stress. Adverse culture conditions during this phase of development could
      therefore alter the mitochondrial genome, with possible long-term consequences
      for the health of the offspring. The findings have relevance for all assisted
      reproduction programmes and for the rapidly emerging field of stem cell
      technologies.

PMID- 15511344
TI  - The Preimplantation Genetic Diagnosis International Society (PGDIS): Guidelines
      for good practice in PGD.

PMID- 15511343
TI  - Outcome of laser-assisted polar body biopsy and aneuploidy testing.
AB  - Polar body biopsy and subsequent fluorescence in-situ hybridization (FISH)
      analysis allows detection of maternally derived chromosomal aneuploidies in human
      oocytes during IVF treatment. The development of a diode laser technique for the
      partial opening of the zona pellucida has stimulated the use of this technique to
      assist polar body biopsy. Laser-assisted polar body biopsy was performed in 140
      IVF cycles from patients of advanced maternal age (> or =35 years). A total of
      921 oocytes were treated by a laser for partial zona opening and polar body
      removal. FISH was performed for chromosomes 13, 16, 18, 21 and 22 and results
      were available for 903 oocytes (98%). In all, 443 oocytes (49.1%) were euploid
      and of these, 293 were fertilized. A total of 214 embryos were transferred in 120
      embryo transfer cycles (1.78 per embryo transfer) resulting in 27 clinical
      pregnancies (22.5% per embryo transfer) with an implantation rate of 15.4%.
      Subsequently, five women aborted (18.5%) and 24 healthy children were born from
      the remaining 22 pregnancies, which gives a take home baby rate of 18.3% per
      transfer cycle. It is concluded that polar body biopsy using a diode laser system
      is as efficient as standard polar body biopsy using zona drilling.

PMID- 15511345
TI  - Increased implantation and pregnancy rates obtained by placing the tip of the
      transfer catheter in the central area of the endometrial cavity.
AB  - The influence of endometrial cavity length (ECL) on implantation and pregnancy
      rates after 400 embryo transfers was studied prospectively in a population with
      the indication of IVF/intracytoplasmic sperm injection (ICSI). The tip of the
      transfer catheter was placed above or below the half point of the ECL in a
      randomized manner. Two analyses were performed: (i) absolute position (AP);
      embryo transfers were divided into three groups according to the distance between
      the end of the fundal endometrial surface and the catheter tip (DTC - distance
      tip catheter): AP1 (n = 212), 10-15 mm; AP2 (n = 158), 16-20 mm; and AP3 (n =
      30), > or =21 mm. (ii) relative position (RP)--embryo transfers were divided into
      four groups according to their RP [RP = (DTC/ECL) x 100]: RP1 (n = 23), < or
      =40%; RP2 (n = 177), 41-50%; RP3 (n = 117), 51-60%; and RP4 (n = 83), > or =61%.
      Analysis based on relative distance revealed significantly higher implantation
      and pregnancy rates (P < 0.05) in more central areas of the ECL. However,
      analysis based on absolute position did not reveal any difference. In conclusion,
      the present results demonstrated that implantation and pregnancy rates are
      influenced by the site of embryo transfer, with better results being obtained
      when the catheter tip is positioned close to the middle area of the endometrial
      cavity. In this respect, previous analysis of the ECL is the fundamental step in
      establishing the ideal site for embryo transfers.

PMID- 15511346
TI  - Partial hydatidiform mole following the transfer of single frozen-thawed embryo
      subsequent to ICSI.
AB  - Hydatiform mole is a gestational trophoblastic disease characterized by the
      dominance of dispermic fertilization. Micromanipulation techniques in assisted
      reproduction technologies have enabled direct evaluation of the zygotes and the
      formation of pronuclei in the zygote. Intracytoplasmic sperm injection (ICSI) of
      oocytes ensures that only a single spermatozoon enters the ooplasma. This study
      reports a case of partial hydatiform mole following the transfer of day 3 frozen
      thawed embryo. ICSI was used as the assisted fertilization method because there
      was male factor infertility due to severe oligoasthenoteratozoospermia. Possible
      predisposing factors for partial hydatidiform mole after ICSI are also discussed.

PMID- 15511347
TI  - Case report: laparoscopic treatment of a ruptured interstitial pregnancy.
AB  - Interstitial pregnancy is a rare but life-threatening condition. A case of a 28
      year-old woman with a partially ruptured interstitial pregnancy treated with
      operative laparoscopy is presented. A laparoscopic cornual resection and a left
      salpingectomy were performed uneventfully. Serum beta-human chorionic
      gonadotrophin concentrations were measured serially at weekly intervals until
      resolved on day 20 postoperatively. It seems, therefore, that laparoscopic
      treatment is still an effective option for management even in ruptured
      interstitial pregnancy, preserving the anatomical integrity of the uterus and
      future fertility, and that rupture of interstitial ectopic pregnancy is not a
      contra-indication for laparoscopy.

PMID- 15511349
TI  - Drug intervention in early pregnancy after assisted reproductive technology.
AB  - Implantation in humans is a complex, closely regulated, highly selective and
      relatively poorly understood process. Humans have the highest rate of miscarriage
      in mammals and various pharmacological manipulations have been used to minimize
      pregnancy losses in both spontaneous pregnancies and pregnancies resulting from
      assisted reproduction technology. The widespread application of protocols using
      numerous drugs in assisted reproduction treatment has led to an increasing number
      of pregnancies exposed to these drugs. The vast majority of these protocols have
      been based on data from a few observational and often retrospective clinical
      studies. This paper reviews the recent literature on drug interventions in early
      pregnancy after assisted reproduction treatment. It is concluded that there are
      still numerous issues about the safety of most drugs for both the women and their
      fetus. In many cases, the benefits are theoretical and the possible long-term
      side-effects are untested. There is an urgent need for more epidemiological
      studies and randomized controlled trials to explore the use, efficacy and side
      effects of both old and new drugs in early pregnancy after assisted reproduction
      treatment.

PMID- 15511350
TI  - Chemiluminescence technique for measuring reactive oxygen species.
AB  - Accurate assessment of reactive oxygen species (ROS) concentrations may help in
      the diagnosis of infertility. The chemiluminescence technique, which uses a
      luminometer to measure ROS, is a common method of assessment. A better
      understanding of the chemiluminescence technique will allow its proper
      application in reproductive medicine. A wide range of luminometers are available
      in the market, and laboratories should select the instruments that suit their
      individual needs.

PMID- 15511351
TI  - Inside the tube and closer to nature?

PMID- 15511352
TI  - [Spirometry in primary care. An unavoidable necessity].

PMID- 15511353
TI  - [Influence of physician and physician list characteristics on influenza
      vaccination rates in older people in a health care area in the community of
      Valencia, Spain].
AB  - OBJECTIVE: To identify the characteristics of physicians and the patients on
      their list related with rates of influenza vaccination in older people, and to
      quantify influenza vaccination coverage in this population group. DESIGN:
      Observational, cross-sectional, multicenter population-based study with primary
      data. PARTICIPANTS: All health centers in the health care area that used
      computerized registries of influenza vaccinations. Vaccination records were
      analyzed for 73 physicians who had been at their present post for at least 2
      years prior to the study, and for 19 457 older people who were vaccinated during
      the 2001-2002 vaccination campaign. SETTING: Primary health care area number 19.
      MAIN MEASURES: Physician's age and sex, whether the physician was certified as a
      specialist in family and community medicine, teaching accreditation, permanent or
      temporary post, length of time in present post, years of professional practice,
      type of health center administration, total number of patients in the physician's
      list, population and percentage of the population >65 years old in the
      physician's list, influenza vaccination rate referred to the total number of
      patients on the physician's list. The criterion evaluated was the influenza
      vaccination rate in older people. Descriptive analysis, bivariate analysis and
      multivariate analysis were used. A P value < .05 was considered statistically
      significant, and 95% confidence intervals were calculated. RESULTS: The overall
      influenza vaccination rate in older people (>65 years) was 50.9%, with
      considerable variability between physicians (from 18% to 77%). Vaccination rates
      were lowest in physicians who had been in their current post for longer (P=.001),
      with larger patient lists (P=.03), with more older people in their list (P=.000),
      and with larger proportions of older people in their list (P=.001). Lower rates
      of vaccination in older people were also associated with lower proportions of all
      patients on the list being vaccinated (P=.000). No significant associations were
      found for any of the other variables. After multivariate analysis only the
      percentage of older people on the physician's list remained significantly
      associated with vaccination rate. CONCLUSIONS: Influenza vaccination rates for
      older people were low and similar to rates reported earlier for this region of
      Spain. The percentage of older people in the list was the only explanatory
      variable in the model, and was inversely proportional to vaccination coverage.

PMID- 15511354
TI  - [Vaccination coverage in adults and health professionals: an unresolved issue in
      primary care].

PMID- 15511355
TI  - [Analysis of disturbances in carbohydrate metabolism in the adult population of
      Yecla (Murcia, Spain)].
AB  - OBJECTIVE: To determine the prevalence of impaired fasting glucose (IFG or GBA),
      impaired glucose tolerance (IGT) and type 2 diabetes mellitus (DM2) in the adult
      population of Yecla. RESEARCH, DESIGN, AND METHODS: We performed a population
      based cross-sectional study (on Primary Care Field) with stratified and random
      sampling (393) from 17 500 residents in Yecla with sanitary card and aged > or
      =30 years. We studied 286 subjects (107 declining to participate) and 261 of them
      (125 men and 136 women) underwent an oral glucose tolerance test (OGTT). MAIN
      MEASUREMENTS: World Health Organization (WHO-99) and American Diabetes
      Association (ADA-97) criteria were used for diagnosis of unknown DM2, GBA and
      IGT. Socio-demographic and anthropometric variables were measured. Plasma lipid,
      glycosylated haemoglobin (HbA1C), microalbuminuria and insulin levels also were
      measured. Insulin resistance was evaluated by the HOMA method. RESULTS: According
      ADA-97 criteria the prevalence of DM2 and GBA was 2.65 (CI+/-1.95) and 4.3% (+/
      2.5) respectively. Underwent an OGTT, the age-adjusted prevalence of DM2, IGT and
      GBA (using the Spanish population of July 02) was 6.7 (95%CI, 3,7-9,7); 13.2
      (95%CI, 9.1-17.3) and 0.2% (95%CI, 0-1.8) respectively. The known DM2 was 5,9%
      (95%CI, 3.8-8) and the global prevalence of DM2 was 12.6% (95%CI, 9.6-15.6). The
      diabetes was associated with overweight, overage and higher insulin, HbA1C and
      insulin resistance levels. CONCLUSIONS: There is a high prevalence of DM2 in
      Yecla (known/unknown 0.87/1). The ADA97 criteria only detected 53% of the unknown
      DM2. The 78% of normoglycemics subjects had overweight or upper-body fat
      distribution and diabetics people had higher BMI (Body Mass Index), Hypertension,
      insulinemia, HbA1C and insulin resistance levels than normoglycemics and IGT
      subjects.

PMID- 15511356
TI  - [Cross-cultural adaptation of a questionnaire for measuring the quality of life
      of patients taking oral anticoagulants].
AB  - OBJECTIVE: To adapt to Spanish culture and language a questionnaire developed to
      evaluate the quality of life of patients taking oral anticoagulation treatment
      (OAT) and to measure its validity. DESIGN: A descriptive observation study to
      validate an instrument to measure health-related quality of life. SETTING:
      Primary and specialist care. PARTICIPANTS: 225 patients, all the patients at our
      centre who were on OAT and a consecutive sample of patients on OAT from the
      referral hospital's haemotology service. MAIN MEASUREMENTS: Direct translation,
      back-translation, and pilot study. Factor analysis and item-dimension grouping,
      internal consistency analysis and analysis of the item-total correlation of the
      definitive version of the questionnaire in Spanish. RESULTS: Mean age was 65
      (SD=13 years); 51% were women; 45.8% were monitored in PC. Validity study: factor
      analysis extracted 5 factors that explained 41.62% of total variance value and
      obtained a grouping different from the original; Cronbach's alpha was .82 overall
      and ran from .56 to .74 in the various dimensions; and item-total correlation
      analysis had statistically significant values, except for question 29.
      CONCLUSIONS: After adaptation to Spanish culture and language of a questionnaire
      developed to evaluate the quality of life of patients taking OAT, it was found to
      be a useful instrument, valid for use in our milieu.

PMID- 15511357
TI  - [Factors of risk of bacterial vaginosis].
AB  - OBJECTIVES: To recognise factors in the host that might condition the appearance
      of the bacterial vaginosis (BV) syndrome, whether gynae-obstetrical factors,
      habits of sexual conduct, hygiene, or other factors. DESIGN: Cross-sectional,
      observational study. SETTING: The study was conducted from January 2002 to June
      2003 in the Primary Care Dr. Jose Castro Villagrana Community Health Centre at
      Tlalpan, Mexico City. PARTICIPANTS: 968 patients with an active sexual life who
      had not taken antibiotics for at least 15 days before the study and who were not
      menstruating at the moment of taking a swab, 859 of whom had a diagnosis of
      cervico-vaginitis and 109 had no symptoms. MAIN MEASUREMENTS: Confidential
      questionnaire and a cervical-vaginal culture. The Amsel criteria were used to
      make the diagnosis of bacterial vaginosis. RESULTS: There was 32.9% prevalence of
      BV. There was a statistically significant association with factors such as age,
      start of active sexual life, the number of sexual relations per week, the number
      of sexual partners, and pregnancy. CONCLUSIONS: Bacterial vaginosis is the main
      cause of infectious processes in the vagina. Its appearance appears to be linked
      to factors involving sexual transmission. Interventions to reduce its prevalence
      and complications are recommended.

PMID- 15511358
TI  - [Chronic obstructive pulmonary disease].

PMID- 15511359
TI  - [Domiciliary assistance dental programs: a current demand].
AB  - INTRODUCTION: The growing demand of dental treatment by institutionalised and
      community-dwelling older adults has made necessary to develop and to evaluate
      domiciliary dental care programmes. OBJECTIVE: Delivering and economic evaluation
      of comprehensive oral health care treatment to older adults living at home or in
      geriatric centres, with problems of transportation. PROGRAM: A domiciliary dental
      care program in a nursing home and in a group of people receiving domiciliary
      care has been develop. During a 10 and 5 month period and working with 210 and 47
      patients respectively, a dentist and hygienist treated the basic dental needs
      with portable instruments. DISCUSSION: In spite of the advantages of those
      programmes, they have a lot of problems such as the economic costs (25,000 Euros
      in the nursing home and 16,700 in their own house), the dental treatment
      limitations and the few patients you can visit in one day. The development of
      domiciliary dental care treatment programmes suppose high economics cost that we
      must pay attention.

PMID- 15511360
TI  - [Anticoagulants for patients with chronic auricular fibrillation: when are they
      indicated?].

PMID- 15511361
TI  - [Guillain-Barre syndrome after immunization with hepatitis A and typhoid
      vaccines].

PMID- 15511362
TI  - [The prevalence of obesity in the population of the city of Huelva].

PMID- 15511363
TI  - [Study of the demand for emergency treatment in pediatric primary care].

PMID- 15511364
TI  - [Is there an association between quality of health care levels and the filling of
      consult forms?].

PMID- 15511365
TI  - [Navigating on the Internet: quality stamps and the semantic web may be a way to
      find the glittering gold].

PMID- 15511366
TI  - [Reflections on the reflections of V. Grenzner on "Family medicine and waiting
      lists"].

PMID- 15511367
TI  - [Helicobacter pylori resistance to metronidazole and clarythromicin: descriptive
      analysis 1997-2000].
AB  - BACKGROUND AND OBJECTIVE: We aimed to assess the resistance of H. pylori to
      clarithromycin and metronidazole, in patients with and without previous
      eradication treatment, in a geographic area from the north of Spain. We also
      analyzed the evolution of resistance rates and its relationships with annual
      antibiotic consumption. PATIENTS AND METHOD: Retrospective study including all
      patients with H. pylori infection and positive culture from January 1997 to
      December 2000. Minimal inhibitory concentrations (MIC) determined by the E test
      were used to report the clarithromycin (MIC > 2 mg/l) and metronidazole (MIC > 32
      mg/l) resistance. RESULTS: A total of 537 clinical H. pylori isolates from
      patients without (n = 389) and with previous eradication treatment (n = 148) were
      studied. H. pylori resistance to clarithromycin and metronidazole was found in
      8.7% (95% CI, 6.1-12) and 13.8% (95% CI, 10.4-17.3) patients without previous
      eradication treatment and in 39.2% (95% CI, 31.3-47.1) and 37.8% (95% CI, 30
      45.7) patients with previous eradication treatment (p < 0.001), respectively.
      Clarithromycin resistance remained stable (1997: 9.7%; 1998: 5.7%; 1999: 11.8%;
      2000: 6.2%) whereas metronidazole resistance decreased over the 4 years study
      period (1997: 38.7%; 1998: 15.1%; 1999: 9%; 2000: 6.9%). We did not observe any
      clear relationship between resistance's evolution and antibiotic annual
      consumption. CONCLUSIONS: In our geographic area, primary resistance rates for
      clarithromycin remained stable whereas resistance for metronidazole decreased
      over the 4 years period.

PMID- 15511368
TI  - [Meningococcal disease in Catalonia, Spain (1990-1997)].
AB  - BACKGROUND AND OBJECTIVE: We aimed to study the behavior of meningococcal disease
      in Catalonia during the period 1990-1997, identifying the possible epidemic
      periods. MATERIAL AND METHOD: All cases reported to the notifiable disease system
      which fulfilled the criteria of confirmed or suspected cases during this period
      were analyzed. RESULTS: The global incidence rate was 4.8/100,000. The incidence
      rate for serogroup B was 1.9/100,000 and for serogroup C 0.8/100,000. The disease
      incidence tended to diminish slightly during the study period, with a constant
      annual growth of 0.11/100,000. The increased incidence of serogroup C cases in
      1996-1997 was associated with an increased incidence in the 10-19 years age
      group. CONCLUSIONS: Globally, in the 1990-1997 period, the disease incidence
      tended to diminish slightly. During the last two years, an increased incidence
      was observed, mostly due to the increase in the number of serogroup C cases. This
      fact was associated with a change in the age pattern of cases, which increased in
      the 10-19 years age group, as observed in other countries and coinciding with
      epidemic periods or greater meningococcal activity.

PMID- 15511369
TI  - [Time trends in prevalence of symptoms of allergic rhinitis in 13-14 year-old
      schoolchildren in 8 areas of Spain between 1993-1994 and 2001-2002 according to
      the International Study of Asthma and Allergies in Childhood (ISAAC)].
AB  - BACKGROUND AND OBJECTIVE: Our goal was to estimate the time trends in the
      prevalence of symptoms of allergic rhinitis (AR) and its geographic variations.
      POPULATION AND METHOD: During 2001-2002, the phase 3 of ISAAC study was carried
      out, and a comparison with the phase 1 (1993-1994) was done. This cross sectional
      study included 30,046 schoolchildren 13-14 years-old from 9 centers (Asturias,
      Barcelona, Bilbao, Cartagena, Castellon, Madrid, Pamplona, Valencia, and
      Valladolid). A questionnaire about rhinitis symptoms self-administered to
      schoolchildren was used at schools and institutes with a participation rate of
      100% to 75.8%. RESULTS: A divergent time trend of AR prevalence symptoms was
      observed with a decrease in Barcelona and Bilbao, a stabilization in Cartagena,
      Pamplona, and Valencia, and an increase in Castellon; Madrid and Valladolid;
      however, there was an overall increase in nasal allergy. The prevalence of
      rhinoconjunctivitis in the past year (Prevalence Ratio [PR] = 1,13; 95%
      Confidence Interval [CI], 1.07-1.19) and nasal allergy ever (PR = 1.22; 95% CI,
      1.15-1.30) increased after adjusting for gender, center and season change. The
      prevalence of rhinoconjunctivitis and nasal allergy varied according to centres,
      Madrid, Asturias, Cartagena and Bilbao exhibiting the higher prevalence. Taken as
      a whole, these data indicate a middle prevalence of AR when compared with other
      countries following an ISAAC methodology. CONCLUSIONS: Two patterns of time trend
      of prevalence of symptoms of AR were observed. The investigation of risk factors
      at local level could be important in order to undertake preventive measures.

PMID- 15511370
TI  - [Prevalence of exposure to environmental tobacco smoke in a urban population].
AB  - BACKGROUND AND OBJECTIVE: We decided to assess the overall prevalence of exposure
      to environmental tobacco smoke (ETS) both in general and according to the
      settings of exposure (home, workplace and leisure time). SUBJECTS AND METHOD: We
      analyzed cross-sectional data of ETS exposure in 1,059 non-smokers included in
      the Cornella Health Interview Survey Follow-up (CHIS-FU) study. We calculated the
      crude and age-standardized prevalence of ETS exposure in general and in the
      different settings. RESULTS: 69.5% (confidence interval [CI] 95%, 64.5%-74.4%) of
      men and 62.9% (CI 95%, 58.1%-67.6%) of women of the sample studied were exposed
      to ETS. We observed a decreasing trend of ETS exposure by age in both sexes. The
      age-standardized prevalence rates of ETS exposure according to the environment
      and sex were: 25.9% (95% CI, 21.8%-30.1%) at home, 55.1% (95% CI, 50.8%-59.4%)
      during leisure time and 34.0% (95% CI, 23.5%-45.6%) in the workplace in men, and
      34.1% (95% CI, 29.8%-38.5%), 44.3% (95% CI, 40.5%-48.2%) and 30.1% (95% CI, 18.9%
      41.3%), respectively, in women. CONCLUSION: In this study, more than half of non
      smokers were exposed to ETS.

PMID- 15511371
TI  - [Utility of a omega 3 fatty acids oral enhanced formula in biochemical parameters
      of head and neck cancer patients].
AB  - BACKGROUND AND OBJECTIVE: To investigate the influence of a arginine and omega3
      fatty acids enhanced supplement in nutritional variables in postsurgical
      ambulatory patients with head and neck tumors. PATIENTS AND METHOD: A population
      of 18 ambulatory postsurgical patients with oral and laryngeal cancer was
      studied. At hospital discharge, postsurgical head and neck cancer patients were
      asked to consume two units per day of a specially designed omega3 fatty acid
      enhanced supplement for a twelve week period. RESULTS: Eighteen patients were
      enrolled in the study. The mean age was 62.5 (11.4) years (1 females/17 males).
      Duration of supplementation was 90.5 (22) days. Significant increases of serum
      protein levels and lymphocites were detected. PCR levels decreased after
      supplementation (71.96 [21.7] md/dl vs 25.9 [11.1] mg/dl; p < 0.05). No
      differences were detected in weight and other anthropometric parameters. A
      positive correlation between omega3/omega6 ratio and kg of fat mass (r = 0.59; p
      < 0.05) and midarm circumference (r = 0.62; p < 0.05) were detected. When the
      population was divided in two groups, group I (ratio omega3/omega6 < 0.51) and
      group II (ratio omega3/omega6 > 0.51), group II showed higher fat mass than group
      I (17.32 [5.3] kg vs 13.8 [5.1] kg; p < 0.05). CONCLUSIONS: This immuno-enhanced
      formula could improve serum protein levels and PCR in ambulatory postoperative
      head and neck cancer patients. An increase in fat mass was detected in patients
      with a high omega3/omega6 intake of polyunsaturated fatty acids.

PMID- 15511372
TI  - [Public health decisions and their consequences].

PMID- 15511373
TI  - [Passive smoking exposure: a little-known risk].

PMID- 15511374
TI  - [Acute pericarditis].

PMID- 15511375
TI  - [A 70 years-old woman with low-grade fever, malaise and pain in left heel].

PMID- 15511376
TI  - [Hyponatremia and syndrome of inappropriate secretion of antidiuretic hormone
      induced by selective serotonin reuptake inhibitors: review of spontaneous
      reports].

PMID- 15511377
TI  - [The epidemiology of asymptomatic pulmonary embolism in cancer patients].

PMID- 15511378
TI  - [Antipsychotic drugs and pregnancy].

PMID- 15511379
TI  - [Allocation of health resources for treatments based on cost-effectiveness].

PMID- 15511381
TI  - [Secondary amyloidosis induced by hydatid cyst].

PMID- 15511384
TI  - [Oral antithrombins and the future of antithrombotic therapy].
AB  - The coagulation cascade leads, via thrombin activation, to the formation of
      fibrin (from its precursor fibrinogen) and platelet thrombus. Several drugs are
      able to interfere with some of the enzymatic factors involved in thrombin
      activation, but thrombin inhibitors (heparin, hirudin and hirulog [bivalirudin])
      are of particular interest because they disrupt the coagulation cascade by acting
      upon one of its final steps. Among the thrombin inhibitors, oral antithrombins
      (ximelagatran) appear to hold great promise for the control of thrombogenicity in
      a number of clinical contexts. Oral antithrombins do not require the
      participation of cofactors to exert their action, and in contrast to thrombin
      inhibitors administered parenterally, they bind specifically to the active site
      of thrombin without interfering with other portions of the molecule. Their
      specificity makes these drugs safe and obviates the need to monitor
      coagulability. Moreover, they show a low rate of interaction with other drugs or
      with foods, and the response to fixed doses is predictable. A number of clinical
      studies have investigated antithrombins for prophylaxis prior to orthopedic
      surgery, in the prevention of cerebrovascular accidents associated with atrial
      fibrillation, and in the control of coronary artery disease. These studies have
      shown that antithrombins are superior to other habitually used treatment options.
      Surprisingly, their use in long-term studies has not been associated with an
      increased rate of bleeding events. Their interesting molecular characteristics
      and considerable therapeutic efficacy and safety suggest that oral antithrombins
      will in the near future become a valuable therapeutic option.

PMID- 15511385
TI  - [Myocardial reperfusion injury].
AB  - Myocardial reperfusion injury is defined as the adverse effects that ensue upon
      restoration of the circulation, which allows blood and nutrients to reach cells
      previously subjected to ischemia. Restoration of blood flow can be accompanied by
      the release of oxygen free radicals, the appearance of intracellular calcium
      overload, and alterations in cell metabolism -all situations that can give rise
      to functional or structural myocardial injury. Clinical signs of injury may
      appear after circulation is restored or after the use of extracorporeal
      circulation during heart surgery, and are manifested as stunned or hibernating
      myocardium after acute coronary syndromes, as the no-reflow phenomenon
      (microvascular injury) after blood flow is restored during angioplasty or after
      <<reperfusion arrhythmia>>, and especially after surgical revascularization. This
      review examines the pathophysiological substrates, clinical manifestations and
      current approaches to treatment for each of these entities.

PMID- 15511386
TI  - [Hypertrophic cardiomyopathy. Genetic basis and clinical implications].
AB  - Thanks to advances in molecular biology during the last decade, the etiology of
      hypertrophic cardiomyopathy has been elucidated. Although more than 150 causal
      mutations of 9 genes that encode contractile proteins have been identified, many
      of the pathogenetic mechanisms remain unclear. In this review we discuss the
      current state of knowledge of the functional effects of some mutations,
      particularly two of the most lethal beta-myosin mutations -Arg403Gln and
      Arg723Gly (Barcelona mutation)- and their contributions to the pathogenesis of
      hypertrophy, sudden death and ischemia. Their potential roles in diagnostic and
      therapeutic strategies are emphasized.

PMID- 15511387
TI  - [Congenital heart defects in the adult: towards nonsurgical interventionism].
AB  - The classical treatment for congenital heart defects in adult patients has been
      surgical correction. Since the publication of Rashkind and Gruntzig's studies,
      interventional cardiology approaches have been developed to treat congenital and
      acquired heart defects. We discuss the current applications of this form of
      treatment and communicate our experience with percutaneous transcatheter
      procedures in adult patients for pulmonary valve stenosis, aortic valve stenosis,
      native coarctation, postsurgical coarctation, peripheral pulmonary artery
      stenosis, atrial septal defect, ventricular septal defect, ductus arteriosus and
      embolization therapy. We conclude that interventional treatment in adults with
      congenital heart defects is safe and feasible, that the indications for this
      approach to treatment are increasing, that it can be undertaken in patients of
      any age including high-risk patients, and that as with all interventional
      procedures, the learning curve must be successfully surmounted.

PMID- 15511388
TI  - [Mitral valve repair today].
AB  - Valve reconstruction, whenever technically feasible, is currently the treatment
      of choice for mitral valve regurgitation. Preoperative transesophageal
      echocardiography discloses the precise location and extent of these lesions,
      making it possible for the surgeon to determine the repairability of the valve
      and to devise a roadmap for the most appropriate surgical maneuvers. Today, the
      aim of surgery should not be limited to abolishing regurgitation, but should also
      comprise restoration of the normal valve geometry in order to ensure durability
      of the repair. This geometric redress involves a) leaflet enlargement or
      reduction, b) replacement of all ruptured, elongated or attenuated chords with
      Goretex sutures, and c) annuloplasty with a flexible, complete ring that prevents
      distension even in the intertrigonal area, maintains the saddle shape of the
      annulus and reduces the dilated anteroposterior diameter of the annulus. These
      techniques have made repair rates approaching 100% possible in patients with
      degenerative valve diseases. For functional ischemic regurgitation, treatment
      currently consists of reduction annuloplasty with a small complete ring performed
      at the time of revascularization. However, despite the improvements seen in these
      patients, late recurrence of insufficiency occurs in about 30% of them. Recent
      evidence that the mechanism of recurrence is the apical and lateral displacement
      of the papillary muscles suggests that in addition to annuloplasty, surgical
      approximation of the papillary muscles may be necessary.

PMID- 15511389
TI  - [Multiresistant bacteria, nosocomially or community acquired?].

PMID- 15511390
TI  - [Fecal colonization by extended-spectrum beta-lactamase-producing Klebsiella
      pneumoniae in a neonatal intensive care unit].
AB  - BACKGROUND: Fecal colonization by multiresistant bacteria can be a source of
      nosocomial infections. The aim of this work was to study fecal colonization by
      Klebsiella pneumoniae in neonatal intensive care unit (NICU) patients and
      investigate the resistance profiles of the strains. METHODS: From May to October
      2001, 11 stool specimens were collected from each patient hospitalized in the
      NICU during this period (425 specimens). Antimicrobial susceptibility was
      determined in K. pneumoniae isolates, and 30 strains resistant to third
      generation cephalosporins were tested by polymerase chain reaction (PCR) to
      detect the blaCTX-M-2 gene. RESULTS: K. pneumoniae grew in the 66% of the
      samples. Extended-spectrum b-lactamases (ESBL) were detected in 82.5% of these
      strains (ESBL-K. pneumoniae), 54.3% of all the strains studied. Among the
      neonates colonized by ESBL-K. pneumoniae (56% of patients), significant
      differences in colonization rates were observed according to gestational age, but
      not according to the mode of delivery or sex. ESBL-K. pneumoniae strains showed a
      high frequency of gentamicin resistance (97.3%) and amikacin resistance (71.4%).
      Nevertheless, they were all susceptible to cefoxitin and imipenem, and more than
      90% were also susceptible to ciprofloxacin and piperacillin-tazobactam. In all
      the cefotaxime-resistant strains, an amplicon consistent with a CTX-M-type beta 
      lactamase was found by PCR. CONCLUSION: A high percentage of NICU patients were
      colonized with ESBL-K. pneumoniae strains belonging to the CTX-M family, with
      elevated rates of aminoglycoside resistance. Gestational age was the only
      variable associated with significant differences in colonization rates.

PMID- 15511391
TI  - [Seroprevalence of antibodies against Treponema pallidum, Toxoplasma gondii,
      rubella virus, hepatitis B and C virus, and HIV in pregnant women].
AB  - INTRODUCTION: The prevalence of antibodies against Treponema pallidum, Toxoplasma
      gondii, rubella virus, hepatitis B virus (HBV), hepatitis C virus (HCV) and human
      immunodeficiency virus (HIV) was investigated in pregnant women. METHODS: With
      the use of several serological methods in samples from women who had their first
      obstetric visit in 2001, we studied the prevalence of serum antibodies against T.
      pallidum, T. gondii, rubella virus, HBV and HCV in 2,929 pregnant women, and anti
      HIV antibodies in the 1,349 women agreeing to this test. RESULTS: Antibodies
      against T. pallidum were not detected in any case. HBsAg was found in 11 patients
      (0.4%), six of whom (54.5%) were not aware of their condition. The presence of
      anti-rubella antibodies was almost universal (99.95%). In the total population,
      18.8% of patients had anti-T. gondii antibodies; only one had a serological
      profile suggesting acute toxoplasmosis. Among the 1,349 women studied, anti-HIV
      antibodies were detected in two intravenous drug abusers who were aware of their
      condition. Anti-HCV antibodies were found in 0.4% of the series, and 36.4% of the
      HCV-positive patients had no knowledge of their condition. CONCLUSIONS: Active
      infection by T. pallidum in pregnant women in Spain is currently exceptional. The
      level of immunization against rubella virus is excellent. Seropositivity to T.
      gondii is lower than rates reported in earlier studies. The prevalence of HBsAg
      and anti-HCV antibodies is around 0.4%, and seropositive status is often
      discovered in routine serological studies performed during pregnancy. HIV
      seropositivity is low, and the pregnant women included in this study were aware
      of their condition.

PMID- 15511393
TI  - [Amoebic liver abscess: observations in seven patients].
AB  - INTRODUCTION: The epidemiological and clinical characteristics of patients with
      amoebic liver abscess are described. METHODS: Laboratory, clinical, and
      epidemiological records of all patients with amoebic liver abscess diagnosed from
      1991 to 2002 at Hospital Universitario Son Dureta (Palma de Mallorca, Spain), a
      980-bed referral hospital in the Balearic Islands, were retrospectively reviewed.
      RESULTS: Seven patients were diagnosed with amoebic liver abscesses and all were
      residing in Mallorca. Two patients had developed the disease after travelling to
      endemic areas (India and Thailand), and another, from Ecuador, had been diagnosed
      four months after coming to Spain from his country of origin. In the remaining
      four patients, no apparent link with endemic areas was observed, nor was travel
      out of Spain recorded. Therefore, these cases were thought to have originated in
      Spain, though this circumstance could not be conclusively proven. Two of the
      seven patients had human inmunodeficiency virus (HIV) infection. CONCLUSIONS: An
      amoebic etiology should be considered in the differential diagnosis of liver
      abscess in our area, even in the absence of a clear related epidemiological
      history.

PMID- 15511392
TI  - [Surveillance of antimicrobial resistance: VIRA study 2004].
AB  - INTRODUCTION: The objective of the study was to know the current situation of the
      antimicrobial sensitivity patterns of the main multi-resistant bacteria and to
      analyze any possible changes with respect to the VIRA study carried out in 2001.
      METHODS: The 40 participating hospitals sent a total of 1,425 microorganisms
      isolated in February 2004, distributed as follows: penicillin-resistant
      Streptococcus pneumoniae (139), methicillin-resistant Staphylococcus aureus
      (289), clinically significant coagulase-negative staphylococci (158), ampicillin
      resistant Enterococcus faecium (89) and Enterococcus faecalis (2), ampicillin
      resistant Haemophilus influenzae (85), ciprofloxacin-resistant Escherichia coli
      (346), Pseudomonas aeruginosa (187), and Acinetobacter baumannii (130). The
      hospitals provided epidemiological data on these microorganisms. Sensitivity was
      determined by the broth microdilution method. RESULTS: The number of highly
      penicillin-resistant pneumococci fell significantly (p < 0.0001) compared with
      the previous study (from 59.8% to 30.2%). Global methicillin-resistance in S.
      aureus was 31.2%, which represents a significant increase (p < 0.001) compared
      with the year 2001 (24.8%). 11.3% of the E. coli strains were extended-spectrum
      beta -lactamase-producers and came from 24 hospitals. One P. aeruginosa isolate
      gave a positive result in the E-test MBL assay, suggesting the presence of
      metallo-beta -lactamases. The strains of imipenem-resistant A. baumannii
      presented cross-resistance with several antibiotics. CONCLUSION: These results
      show how the multi-resistant bacteria included in the study represent a growing
      problem in our hospitals. This emphasizes the importance of resistance
      surveillance systems and the correct use of antimicrobial agents.

PMID- 15511395
TI  - [Advances in the diagnosis and treatment of the infection by the hepatitis B
      virus].
AB  - Infection by the hepatitis B virus (HBV) is a significant cause of morbidity and
      mortality, mainly due to evolvement to cirrhosis and hepatocellular carcinoma.
      The prevalence and genotypic distribution of HBV infection has marked geographic
      differences. HBV infection is a very dynamic process, with a phase of immune
      tolerance and high viral replication, followed by HBeAg clearance, not always
      accompanied by complete suppression of HBV replication. The latter situation
      corresponds to negative HBeAg hepatitis, which represents a group relatively
      resistant to therapy. The three approved drugs for the treatment of HBV infection
      (interferon alpha, lamivudine and adefovir) have limited efficacy. Relapses are
      more common with lamivudine and adefovir, requiring often long-term treatment.
      While the selection of lamivudine resistance mutations is frequent, adefovir has
      a high genetic barrier. HIV infection negatively impacts on HBV disease,
      requiring these coinfected patients strategies aimed to manage both viruses.

PMID- 15511394
TI  - [Liver transplantation in patients with HIV infection: a reality in 2004].
AB  - According to current estimates, there are 60,000 to 80,000 HIV and HCV coinfected
      individuals in Spain, and 5,000 to 10,000 HIV and HBV coinfected individuals.
      Among these patients, 10% to 15% have liver cirrhosis. Thus, end-stage liver
      disease is one of the major causes of death in our country. Liver transplantation
      is the only therapeutic option for these patients. Accumulated experience in
      North America and Europe in the last five years indicates that three-year
      survival in HIV-positive liver transplant recipients is similar to that of HIV
      negative recipients. The selection criteria for HIV transplant candidates
      includes the following: no history of opportunistic infections, CD4 lymphocyte
      count higher than 100 cells/mm3, and HIV viral load suppressible with
      antiretroviral treatment. In Spain, where the majority of patients are former
      drug abusers, complete abstinence from heroin or cocaine use during two years is
      also required, with the possibility of the patient being in a methadone program.
      To date 26 hepatic transplants have been performed in the same number of
      patients, with only two deaths (7%) after a median follow-up of eight months (1
      28). The main problems in the post-transplantation period in all the series has
      been recurrent HCV infection, which is the principle cause of post
      transplantation mortality, and pharmacokinetic and pharmacodynamic interactions
      between the antiretroviral and immunosuppressive agents. There is little
      experience with pegylated interferon and ribavirin treatment in this population.

PMID- 15511396
TI  - [Nodular lesions of the posterior foot in a renal transplant patient].

PMID- 15511397
TI  - [Helminthiasis in a 71-year-old man, an infrequent condition in our setting].

PMID- 15511398
TI  - [Vertical transmission of HCV infection by HIV-negative mothers].

PMID- 15511399
TI  - [Endocarditis due to the Neisseria elongata subspecies nitroreducens].

PMID- 15511401
TI  - [Systemic lupus erythematosus therapy. Antimalarials in inflammatory diseases].

PMID- 15511402
TI  - [Pharmacoeconomic analysis of patients with acute exacerbation of chronic
      bronchitis treated with telithromycin or cefuroxime-axetil].
AB  - INTRODUCTION: A pharmacoeconomic analysis was done to compare the efficiency of
      two treatments in the acute exacerbation of chronic bronchitis: telithromycin and
      cefuroxime-axetil. METHODS: Restrospective analysis, modeled through a decision
      tree. The effectiveness of the treatments was estimated through a randomized and
      double-blind clinical trial in which 800 mg/day (5 days) of telithromycin were
      compared with 1,000 mg/day (10 days) of cefuroxime-axetil in patients with acute
      exacerbation of chronic bronchitis (140 and 142 patients, respectively).
      Resources use was estimated from clinical trial and from Spanish data, and the
      unit costs through a health costs dabatase. The model was validated by a panel of
      Spanish clinical experts. RESULTS: Since the clinical trial was designed to
      demonstrate equivalence, there were no significant differences of effectiveness
      among both treatments (with a rate of clinical cure of 86.4% and 83.1%,
      respectively) which means that an analysis of costs minimization was done. In the
      average case, the average cost of the disease by patient was 174.83 Euros with
      telithromycin and 194.68 Euros with cefuroxime-axetil (a difference of 19.85
      Euros). The results were maintained in the analysis of sensitivity, with
      favorable differences for telithromycin that ranged between 18.04 Euros and 22.25
      Euros. CONCLUSIONS: With telithromycin up to 22 Euros by patient with acute
      exacerbation of chronic bronchitis could be saved, in comparison with cefuroxime
      axetil.

PMID- 15511403
TI  - [Variables associated with functional recovery and post-discharge
      institutionalization of elderly cared in an average stay geriatric unit].
AB  - BASIS: To describe the evolution and results of the rehabilitation of elderly
      disabled cared in an average stay geriatric unit, and to define the factors
      associated with functional improvement and post-discharge institutionalization.
      PATIENTS AND METHOD: Observational longitudinal study in 459 patients with
      functional disability consecutively hospitalized between May 2000 and December
      2001. Basal variables collected included the clinical, functional, mental, and
      sociodemographic manifestations previous to the admission. The favorable
      functional response (defined as a functional gain during the admission of > or =
      20 points in the Barthel index) and the post-discharge institutionalization were
      regarded the main result variables. RESULTS: The average age of patients was
      80.56 (SD: +/- 7.45) years, 64.9% were women and 81% came from acute hospital
      units; the main cause of disability was stroke (48.5%) followed by orthopedic
      pathology (26.2%) and immobility for different causes (23.5%). 72.5% of patients
      get functional improvement and 16.4% were institutionalized after the discharge.
      The main independent risk factors for poor functional response found in the
      multivariate analysis were a scoring in Pfeiffer's cognitive test of 5-7 points
      (OR: 0.42; 95% CI: 0,22-0.78) and > or = 8 (OR: 0.29; 95% CI: 0.12-0.71), and a
      scoring in Barthel's index < 60 prior to the deterioration (OR: 0.36; 95% CI:
      0.14-0.93). Independent risk factors for institutionalization after the discharge
      were age (OR: 1.06; 95% CI: 1.01-1.12), and a scoring in the Gijon's
      sociofamiliar scale > or = 9 (OR: 6.83; 95% CI: 1.91-24.47). A functional
      disability after the discharge in the Barthel's index < 40 also was independently
      associated to post-discharge institutionalization (OR: 3,07; 95% CI: 1.04-10.06).
      CONCLUSIONS: Most of elderly with recent disability benefit functionally from
      care in specific hospital geriatric units. Moderate or severe cognitive
      deterioration after hospitalization is associated to lower recovery probability.
      Very advanced age, higher social precariousness and severe disability after
      discharge are associated with higher risk of institutionalization.

PMID- 15511404
TI  - [Prognostic value of antibodies anti-Chlamydia pneumoniae in ischemic heart
      disease].
AB  - INTRODUCTION AND OBJECTIVES: Coronary artery disease has been related to
      infection by Chlamydia pneumoniae even only in a few studies the association
      between presence of antibodies to this microorganism and the prognosis of
      patients with ischemic heart disease has been assessed. The objective of our
      study was to assess the impact of positivity of anti-Chlamydia pneumoniae
      antibodies in the morbidity and mortality associated to ischemic heart disease.
      METHODS: 249 patients with ischemic cardiopathy were evaluated (97 with
      myocardial infarction, 83 with unstable angina and 69 with stable angina),
      recluted along 1 year and with 3-year follow-up. IgG anti-Chlamydia pneumoniae
      antibodies were measured with microimmunofluorescence. The cut off point
      considered for positive serology was set in 1/64. RESULTS: In the group of 97
      patients with acute myocardial infarction, 43% showed positive titers of IgG
      antibody to C. pneumoniae. We observed a statistically significant association (p
      = 0.007) between positive serology and higher survival of acute myocardial
      infarction patients. A logistic regression was carried out with mortality, age,
      and serology as variables; age was the only variable that explained mortality (p
      = 0.0012), and the serology lost its statistical meaning. In the groups of 83
      patients with unstable angina and of 69 patients with stable angina, 42% and 58%,
      respectively, showed positive serology for C. pneumoniae. We did not find a
      statistically significant association in both groups between positive serology to
      C. pneumoniae and the prognostic factors related to morbidity and mortality
      (rehospitalization and mortality). CONCLUSIONS: The presence of IgG antibodies to
      C. pneumoniae is not a marker of morbidity and mortality in our population of
      patients with ischemic heart disease.

PMID- 15511405
TI  - [Intolerance to hydroxychloroquine marketed in Spain (Dolquine) in patients with
      autoimmune conditions].
AB  - BASIS: A significant proportion of our patients has described to have problems
      from tolerance to Dolquine, a new presentation of hydroxychloroquine recently
      marketed in Spain, compared to Plaquenil. The objective was to know the
      tolerability and the adverse effects of this new presentation. PATIENTS AND
      METHOD: A cross-sectional multicenter study on 133 patients treated with Dolquine
      was conducted. RESULTS: Of the 133 patients (87% women; average age [AA]: 32.9
      [15.4] years) who received Dolquine during an average period of 6.7 (1.4) months,
      32 patients (24%) described to have more problems with this drug in comparison
      with other antimalarial. The adverse effects experienced were: bitter taste
      (62.4%), difficulty in swallowing the tablet (13.5%), dyspepsia (9.8%), nausea
      (7.5%), vomiting (1.5%), pruritus (1.5%), diarrhea (0.7%), and instability
      feeling (0.7%). The presence of gastrointestinal adverse effects was not related
      to the consumption of gastroerosive drugs, gastric protectors, or a high number
      of drugs. The attrition rate was 9.8%. Conclusions. Dolquine induces lower
      tolerance and more gastrointestinal adverse effects than Plaquenil, pointing out
      its bitter taste and the difficulty in swallowing it. Despite this higher
      intolerance there was not an increase in the attition rate from the antimalarial
      treatment in comparison to other series.

PMID- 15511406
TI  - [The role of angiotensin-converting enzyme inhibitors (ACEI) in patients with
      cardiovascular risk].

PMID- 15511407
TI  - [The role of imaging diagnosis in biliary ileus].

PMID- 15511408
TI  - [Modulation of renin-angiotensin system for vascular protection in hypertensive
      patients and in patients with diabetic nephropathy].
AB  - Angiotensin II intervenes in the genesis of arterial hypertension and in the
      organic damage associated to arterial hypertension and to diabetes mellitus.
      Because of its proinflammatory effects, angiotensin II participates in the
      process of atherogenesis. Hemodynamic mechanisms and several citokines whose
      production is promoted by angiotensin II participate in left ventricular
      hypertrophy associated to arterial hypertension. Angiotensin II also contributes
      to renal damage secondary to diabetes mellitus by its actions in the
      intraglomerular hemodynamics and by its glomerular and interstitial fibrogenic
      effects. The intervention on the renin-angiotensin system should be part of
      therapy of patients with high cardiovascular risk with hypertensive disease
      and/or diabetes mellitus.

PMID- 15511409
TI  - [Short-term hemiparesis].

PMID- 15511410
TI  - [Extensive panniculitis in a 64-year-old woman].

PMID- 15511411
TI  - [Central cyanosis in a young woman].

PMID- 15511412
TI  - [Hyperhomocysteinemia and multiple arterial thrombosis in a young patient with
      mutation of methylentetrahydrofolate reductase C677T].

PMID- 15511413
TI  - [Consultation on diagnostic and therapeutic decisions in Internal Medicine].

PMID- 15511414
TI  - [High output heart failure and pulmonary acute edema as presentation of
      thyrotoxicosis secondary to toxic multinodular goiter].

PMID- 15511415
TI  - [Patients advice consultation versus diagnostic and therapeutic advice
      consultation. Different ways for the same efficiency].

PMID- 15511416
TI  - Survival after simultaneous left ventricular free wall, papillary muscle, and
      ventricular septal rupture.
AB  - Cardiac rupture is a catastrophic complication of acute myocardial infarction.
      The three potential sites of rupture are the left ventricular free wall,
      interventricular septum, and papillary muscle. Without rapid surgical correction,
      each of these complications typically leads to cardiogenic shock, multiorgan
      failure, and death. Postmortem analysis has identified a small number of cases in
      which myocardial infarction led to rupture at more than one of these sites;
      however, there are no reports of survival from such an event. We report a case
      involving rupture at all three sites in the same patient, emphasizing the
      importance of transesophageal echocardiography and surgical management.

PMID- 15511417
TI  - Unrecognized left ventricular thrombus during reoperative coronary artery bypass
      grafting.
AB  - Left ventricular thrombus after myocardial infarction is relatively common but
      rarely threatening enough to warrant surgical removal at the time of coronary
      revascularization. The rare cases of ventricular thrombectomy described in the
      literature involve a pedunculated thrombus. We describe an urgent coronary
      revascularization procedure in a patient who had unrecognized left ventricular
      thrombus. The large clot was detected by transesophageal echocardiography after
      decannulation in a hemodynamically unstable patient. The thrombus was removed
      after placing the patient back on cardiopulmonary bypass emergently. He recovered
      and was discharged with no neurologic sequelae. Aggressive removal of clot using
      cardiopulmonary bypass is warranted even for the critically ill patient.

PMID- 15511418
TI  - Surgical management of complications of percutaneous coronary rotational
      atherectomy interventions.
AB  - Percutaneous coronary interventions have progressed from angioplasty and
      intracoronary stents to the more aggressive rotational atherectomy devices. These
      technically complex procedures are typically performed on the more diseased
      anatomy, which causes the likelihood of complications to be more common. In this
      report, we present our experience with three unusual complications and their
      surgical management.

PMID- 15511419
TI  - Pacemaker lead thrombosis treated with atrial thrombectomy and biventricular
      pacemaker and defibrillator insertion.
AB  - Right atrial thrombosis and pulmonary embolism are infrequent complications of
      pacemaker insertion. We report a patient with a large mobile thrombus on an
      endocardial DDD pacing lead and probable pulmonary embolism. We believe that this
      is the first case of pacemaker lead thrombosis in which treatment included
      insertion of an epicardial biventricular pacemaker and an implantable
      cardioverter-defibrillator.

PMID- 15511420
TI  - Treatment of iatrogenic injury of membranous trachea with intercostal muscle
      flap.
AB  - Iatrogenic injuries of the membranous trachea are rare but potentially lethal,
      and most commonly require surgical treatment. Such injuries occur
      intraoperatively during specific thoracic surgery procedures or are associated
      with endotracheal anesthesia. Special technical difficulties in managing them
      surgically are encountered when lacerations are in proximity to the rigid rings
      of the trachea because of the lack of membranous tissue distal to the tear. We
      describe our technique used in a patient with such an iatrogenic tracheal injury
      during resection of invasive lung carcinoma.

PMID- 15511421
TI  - Residency training for the future, not the past.

PMID- 15511422
TI  - Clopidogrel and postoperative bleeding.

PMID- 15511423
TI  - Are there enough jobs in cardiothoracic surgery? The thoracic surgery residents
      association job placement survey for finishing residents.
AB  - BACKGROUND: Applications to cardiothoracic surgery training programs have
      declined. Anecdotal evidence suggests limited job availability for residents
      completing cardiothoracic training, which may contribute to this decline. This
      survey sought to document the experience of current, graduating residents.
      METHODS: In June 2003, the Thoracic Surgery Residents Association surveyed
      residents completing accredited cardiothoracic training or additional
      subspecialization, utilizing a web-based survey hosted by CTSNet. Resident
      participation was voluntary and anonymous. RESULTS: Of the estimated 140
      graduates, 89 responded. The majority were male (91.0%, n = 81), married (80.0%,
      n = 71), and had children (61.0%, n = 54). Average age was 36.2 years old, and
      mean educational debt was less than 50K dollars. Of the 89 respondents, 77
      initially sought jobs and 12 sought additional training. For residents seeking
      jobs, 19.5% (n = 15) received no offers and 13 of these ultimately pursued
      additional training. Acquired jobs were in private (53.0%, n = 34) or academic
      practice (47.0%, n = 30), with 73.4% (n = 47) involving general thoracic surgery.
      Most would again choose cardiothoracic surgery as a career (75.5%, n = 67), and
      62.0% (n = 55) would again submit the same match list. However, 87.0% (n = 77)
      believed that the number of trainees should be decreased, 81.0% (n = 72) believed
      that reimbursement for cardiothoracic surgery is inadequate, and 77.5% (n = 69)
      believed that excessively low reimbursement will result in restricted access or
      decreased quality for patients. CONCLUSIONS: Most cardiothoracic residents were
      successful in finding employment after training. A substantial percentage,
      however, pursued additional training due to lack of job opportunities. Although
      most finishing residents were satisfied with training and career choice,
      significant concerns exist regarding job opportunities and compensation. These
      conditions may lead to difficulty in recruitment to the specialty.

PMID- 15511424
TI  - EuroSCORE predicts intensive care unit stay and costs of open heart surgery.
AB  - BACKGROUND: This study aimed to determine whether the preoperative risk
      stratification model EuroSCORE predicts the different components of resource
      utilization in open heart surgery. METHODS: Data for all adult patients
      undergoing heart surgery at the University Hospital of Lund, Sweden, between 1999
      and 2002 were prospectively collected. Costs were calculated for the surgery and
      intensive care and ward stay for each patient (excluding transplant cases and
      patients who died intraoperatively). Regression analysis was applied to evaluate
      the correlation between EuroSCORE and costs. The predictive accuracy for
      prolonged postoperative intensive care unit (ICU) stay was assessed by the Hosmer
      Lemeshow goodness-of-fit test. The discriminatory power was evaluated by
      calculating the areas under receiver operating characteristics curves. RESULTS:
      The study included 3,404 patients. The mean cost for the surgery was 7,300
      dollars, in the ICU 3,746 dollars, and in the ward 3,500 dollars. Total cost was
      significantly correlated with EuroSCORE, with a correlation coefficient of 0.47
      (p < 0.0001); the correlation coefficient was 0.31 for the surgery cost, 0.46 for
      the ICU cost, and 0.11 for the ward cost. The Hosmer-Lemeshow p value for
      EuroSCORE prediction of more than 2 days' stay in the ICU was 0.40, indicating
      good accuracy. The area under the receiver operating characteristics curve was
      0.78. The probability of an ICU stay exceeding 2 days was more than 50% at a
      EuroSCORE of 14 or more. CONCLUSIONS: In this single-institution study, the
      additive EuroSCORE algorithm could be used to predict ICU cost and also an ICU
      stay of more than 2 days after open heart surgery.

PMID- 15511425
TI  - Invited commentary.

PMID- 15511426
TI  - Does clopidogrel increase blood loss following coronary artery bypass surgery?
AB  - BACKGROUND: Clopidogrel (Plavix) is a potent inhibitor of platelet aggregation
      used concomitantly with percutaneous coronary interventions and in patients with
      acute coronary syndromes. Its favorable effects on preventing thrombus formation
      may have deleterious effects on hemostasis in patients undergoing coronary
      surgery. METHODS: Data were collected prospectively on 312 consecutive urgent or
      emergent coronary artery bypass patients from July 1999 through April 2001 at a
      tertiary care center. Patients were stratified into three groups: clopidogrel
      within 4 days of operation (n = 41), clopidogrel continued until 5 to 8 days
      before operation (n = 39), and clopidogrel discontinued more than 8 days before
      operation or were never taking clopidogrel (n = 232). RESULTS: Preoperative and
      intraoperative characteristics were similar among all groups. Mediastinal and
      pericardial chest tube losses in the first 24 hours were 1,044 +/- 750 mL in the
      clopidogrel within 4 days group, 528 +/- 250 mL in the clopidogrel 5 to 8 days
      group, and 573 +/- 329 mL in the clopidogrel more than 8 days group (p < 0.01).
      The mean total blood product transfusions were 12.2 +/- 15.4 U, 1.2 +/- 2.0 U,
      and 2.6 +/- 5.7 U, respectively (p < 0.001). Reoperation for bleeding was noted
      in 14.6%, 2.6%, and 1.7%, respectively (p = 0.002). The median hospital lengths
      of stay for the three groups were 9 days, 7 days, and 7 days, respectively (p =
      0.018). There were no statistically significant differences in mortality rate,
      myocardial infarction, stroke, mediastinitis, or postoperative renal failure
      among the groups. Multivariable analysis revealed that clopidogrel within 0 to 4
      days of operation was an independent predictor of transfusion requirements (OR
      4.22, 95% confidence interval [CI] 2.07, 9.34, p = 0.001), intensive care unit
      (ICU) length of stay (OR 3.14, 95% CI 1.40, 7.04, p = 0.006), and total hospital
      length of stay (coefficient 7.65, se 2.41, p = 0.002). CONCLUSIONS: Clopidogrel
      within 4 days of coronary bypass surgery is associated with increased blood
      losses and reoperation for bleeding and, according to multivariable models, is an
      independent risk factor for increased transfusion requirements and prolonged ICU
      and hospital length of stay.

PMID- 15511427
TI  - Allogenic blood transfusion does not predispose to infection after cardiac
      surgery.
AB  - BACKGROUND: Many retrospective studies report increased postoperative infection
      after allogenic blood transfusion. To investigate this phenomenon, we
      prospectively studied 232 patients undergoing cardiac surgery. METHODS: Patients
      were screened daily for evidence of culture positive infections. Wounds were
      examined daily and defined on the ASEPSIS score. Chest radiographs and white cell
      counts and differentials were recorded on days 1, 2, and 4. The use of blood
      products was monitored blindly and independently. Patients were grouped according
      to transfusion status and compared using chi2 or Fisher's test. Logistic
      regression analyses were performed to identify predictors of transfusion and
      infection. RESULTS: Of 232 patients, 116 (50%) received blood product
      transfusion. Patients receiving blood had lower preoperative hemoglobin, were
      older, with a greater proportion of urgent/emergency or revision surgery, and
      were higher risk. Despite this, there were no differences in the frequency of
      chest infection (20% versus 15%, p = 0.38), urinary infection (3.5% versus 5.3%,
      p = 0 0.75), wound infection (3.5% versus 8.0%, p = 0.16), or overall infection
      (28% versus 30%, p = 0.89) comparing the transfused versus untransfused groups.
      There was no evidence to suggest that administration of blood products was
      associated with infection (odds ratio 0.92, p = 0.77). CONCLUSIONS: The
      administration of blood per se did not lead to increased postoperative infection.
      Clinicians should reconsider withholding blood transfusion in patients solely
      owing to concerns of predisposition to infection.

PMID- 15511428
TI  - Identifying patients at risk of intraoperative and postoperative transfusion in
      isolated CABG: toward selective conservation strategies.
AB  - BACKGROUND: Allogeneic blood product use during cardiac operation is often
      reported to exceed 40% despite published guidelines and costly blood conservation
      strategies. We developed a predictive model, based on eight preoperative risk
      factors, of allogeneic blood product transfusion rates in patients undergoing a
      cardiac procedure. METHODS: All 3,046 consecutive, isolated coronary artery
      bypass graft (CABG) procedures at a university hospital from 1995 to 1998 were
      included. A logistic regression model was created to identify independent
      predictors of allogeneic blood product transfusion. This model was validated
      using a prospective patient sample. RESULTS: Overall use of allogeneic blood
      products was 23% with a crude operative mortality of 2.1%. In isolated, elective,
      first-time CABG cases, 16.9% received allogeneic blood products. Independent
      predictors of blood product usage in CABG patients were preoperative hemoglobin
      12.0 or less, emergent operation, renal failure, female sex, age 70 years or
      older, left ventricular ejection fraction 0.40 or less, redo procedure, and low
      body surface area. Prospective validation of this model on 2,117 consecutive
      isolated CABG patients demonstrated an observed-to-expected allogeneic blood
      product transfusion rate ratio of 1.06. CONCLUSIONS: This internally validated
      logistic regression risk model is a sensitive and specific predictor of
      allogeneic blood product use in patients undergoing isolated CABG. Utilization of
      this model allows for preoperative risk stratification and may allow for more
      rational resource allocation of costly blood conservation strategies and blood
      bank resources.

PMID- 15511429
TI  - Invited commentary.

PMID- 15511430
TI  - Aortic atheroma burden and cognitive dysfunction after coronary artery bypass
      graft surgery.
AB  - BACKGROUND: Neurocognitive dysfunction (NCD) after coronary artery bypass graft
      (CABG) surgery is a common problem. Atherosclerotic disease of the aorta is a
      known risk factor for stroke after cardiac surgery, but its relationship to NCD
      is unclear. This study investigates the relationship between aortic
      atherosclerotic disease and NCD after CABG. PATIENTS AND METHODS: Patients
      undergoing primary elective CABG were enrolled in an ongoing investigation of NCD
      after CABG. Intraoperative transesophageal echocardiography (TEE) of the thoracic
      aorta was performed and analyzed off-line to quantify atheroma burden.
      Neurocognitive evaluation was performed, both preoperatively and at 6 weeks after
      surgery. Multivariable linear regression (controlling for age, years of
      education, and base line cognitive index) was used to determine the relationship
      between NCD and atheroma burden in the ascending, arch, and descending aorta.
      RESULTS: One hundred sixty-two patients who had a complete neurocognitive
      evaluation and adequate TEE images were studied. No significant relationship was
      found between NCD and atheroma burden in the ascending (p = 0.22), arch (p =
      0.89) or descending aorta (p = 0.64). CONCLUSIONS: Although the etiology of NCD
      is likely multifactorial, our results suggest that aortic atherosclerosis may not
      be the primary factor in the pathogenesis of post-CABG cognitive changes.

PMID- 15511431
TI  - Invited commentary.

PMID- 15511432
TI  - The impact of aortic manipulation on neurologic outcomes after coronary artery
      bypass surgery: a risk-adjusted study.
AB  - BACKGROUND: Cerebral embolization of atherosclerotic plaque debris caused by
      aortic manipulation during conventional coronary artery bypass grafting (CABG) is
      a major mechanism of postoperative cerebrovascular accidents (CVA). Off-pump CABG
      (OPCABG) reduces stroke rates by minimizing aortic manipulation. Consequently,
      the effect of different levels of aortic manipulation on neurologic outcomes
      after CABG surgery was examined. METHODS: From January 1998 to June 2002, 7,272
      patients underwent isolated CABG surgery through three levels of aortic
      manipulation: full plus tangential (side-biting) aortic clamp application (on
      pump surgery; n = 4,269), only tangential aortic clamp application (OPCABG
      surgery; n = 2,527) or an "aortic no-touch" technique (OPCABG surgery; n = 476).
      A risk-adjusted logistic regression analysis was performed to establish the
      likelihood of postoperative stroke with each technique. Preoperative risk factors
      for stroke from the literature, and those found significant in a univariable
      model were used. RESULTS: A significant association for postoperative stroke
      correspondingly increasing with the extent of aortic manipulation was
      demonstrated by the univariable analysis (CVA incidence respectively increasing
      from 0.8% to 1.6% to a maximum of 2.2%, p < 0.01). In the logistic regression
      model, patients who had a full and a tangential aortic clamp applied were 1.8
      times more likely to have a stroke versus those without any aortic manipulation
      (95% confidence interval: 1.15 to 2.74, p < 0.01) and 1.7 times more likely to
      develop a postoperative stroke than those with only a tangential aortic clamp
      applied (95% confidence interval: 1.11 to 2.48, p < 0.01). CONCLUSIONS: Aortic
      manipulation during CABG is a contributing mechanism for postoperative stroke.
      The incidence of postoperative stroke increases with increased levels of aortic
      manipulation.

PMID- 15511433
TI  - Particle separation using ultrasound can radically reduce embolic load to brain
      after cardiac surgery.
AB  - BACKGROUND: Microembolism during cardiopulmonary bypass has been suggested as
      being the predominant cause of neurocognitive disorders after cardiac surgery.
      Shed blood, normally retransfused into the patient during cardiopulmonary bypass,
      is a major source of lipid microemboli in the brain capillaries. A newly
      developed technique based on acoustic standing-wave separation of particles in
      fluid in microchannels, with the capacity to remove lipid particles in blood, is
      presented. METHODS: A separator consisting of eight parallel, high-fidelity
      microfabricated channels was actuated with an ultrasound field to create a
      standing wave. Three different concentrations of lipid particles (diameter, 0.3
      microm) were added to blood samples with increasing hematocrits and introduced
      into the separator channels to separate lipid particles and erythrocytes.
      RESULTS: The mean separation rates for lipid particles were 81.9% +/- 7.6% and
      for erythrocytes 79.8% +/- 9.9%, and both were related to the hematocrit level of
      the incoming blood sample. The procedure was atraumatic and did not cause
      hemolysis. CONCLUSIONS: Particle separation by means of an acoustic standing-wave
      technique can be used for atraumatic and effective removal of lipid particles
      from blood, with the possible clinical implication of reducing neurocognitive
      complications after cardiopulmonary bypass.

PMID- 15511434
TI  - Invited commentary.

PMID- 15511435
TI  - Improving outcomes in coronary surgery: the impact of echo-directed aortic
      cannulation and perioperative hemodynamic management in 500 patients.
AB  - BACKGROUND: Stroke and death continue to occur perioperatively associated with on
      pump and off-pump coronary artery bypass grafting surgery (CABG) procedures. We
      report on a prospectively implemented multifaceted strategy to improve short-term
      outcomes associated with on-pump CABG. METHODS: Five hundred consecutive patients
      from a single teaching institution undergoing standardized on-pump nonreoperative
      CABG between June 1996 and July 2003 were entered into the New York State Cardiac
      Surgery database, a verified comprehensive clinical registry. Risk factors and
      outcomes were analyzed and compared with the statewide New York State CABG
      registry. All patients underwent intraoperative transesophageal echocardiography
      to guide distal aortic cannulation and high flow-high pressure cardiopulmonary
      bypass perfusion, arterial filtration, centrifugal pump perfusion, and membrane
      oxygenation. Intraoperative and early postoperative blood pressures were
      continuously targeted to match the patient's preoperative range. RESULTS: The
      mean patient age was 63.5 years, 335 (67%) were male, and 320 (64%) were deemed
      to be of elective surgical priority. The mean ejection fraction was 0.434, with
      255 (51%) having sustained a prior myocardial infarction. The mean
      cardiopulmonary bypass time was 95 minutes with an ischemic time of 51 minutes to
      accomplish a mean of 3.19 grafts/patient. The predicted group mortality was
      2.28%, which was greater than the simultaneously measured 1.98% New York
      statewide CABG mortality during the same period for comparable patients (p <
      0.05). There was no in-hospital or 30-day mortality nor were there any
      perioperative strokes in this group (p < 0.05). The mean postoperative hospital
      length of stay was 3.61 days with a 5.1% 30-day readmission rate. CONCLUSIONS: A
      standardized approach to CABG using echocardiographic guided aortic cannulation
      and perioperative hemodynamic management reduces perioperative stroke and death
      associated with on-pump coronary surgery.

PMID- 15511436
TI  - Invited commentary.

PMID- 15511437
TI  - Role of intraoperative transesophageal echocardiography in patients having
      coronary artery bypass graft surgery.
AB  - BACKGROUND: Previous studies have shown that intraoperative transesophageal
      echocardiography provides important preoperative and postoperative information in
      various cardiac and noncardiac surgeries that may alter patient management and
      outcome. The role of intraoperative transesophageal echocardiography in patients
      in whom isolated coronary artery bypass graft surgery is anticipated has been
      reported only in small selected groups. This study was designed to prospectively
      evaluate the role of intraoperative transesophageal echocardiography in a large,
      nonselected group of patients undergoing primarily coronary artery bypass graft
      surgery. METHODS: From January 2001 to December 2003, 474 consecutive patients
      (76% men, 24% women) aged 30 to 89 years (mean age of 70 +/- 10 years) who were
      undergoing coronary artery bypass graft surgery had prebypass and postbypass
      intraoperative transesophageal echocardiography. New findings and alterations in
      the surgical plan were documented prospectively. RESULTS: New prebypass findings
      were found in 10% of patients, and the surgical plan was altered in 3.4% of
      patients. New postbypass findings were found in 3.2% of patients, altering the
      surgical plan in 2% of patients. CONCLUSIONS: This large consecutive,
      nonselected, prospective study reveals the significant impact of intraoperative
      transesophageal echocardiography in patients having coronary artery bypass graft
      surgery as a primary procedure. New findings (prebypass and postbypass) were
      found in 13% of patients overall, and the surgical plan was altered in 5.5% of
      patients. This study supports the use of intraoperative transesophageal
      echocardiography in patients undergoing primarily coronary artery bypass graft
      surgery.

PMID- 15511438
TI  - Total arterial off-pump coronary surgery: time to change our habits?
AB  - BACKGROUND: This was a single-institutional study about total arterial myocardial
      off-pump coronary artery bypass grafting (OPCAB) surgery. METHODS: We studied 569
      multivessel coronary artery bypass patients who underwent total arterial OPCAB
      (42.7% of total OPCAB and 42.4% of total coronary artery bypass grafting
      operations) between June 2000 and June 2003. Risk profile was moderate to high,
      with a mean logistic EuroSCORE of 6.2 +/- 5.1. Univariate and multivariate
      analysis were used to find determinants of in-hospital death, neurologic events,
      and cardiac-related events at follow-up. Overall survival was determined by the
      Kaplan-Meier method. Linearized complication rates at follow-up are reported.
      RESULTS: In-hospital mortality was 2.3%. At univariate analysis, significant
      determinants of in-hospital mortality were age, logistic EuroSCORE greater than
      15, diabetes, extracardiac arteriopathy, New York Heart Association class IV,
      ejection fraction less than 30%, and intraaortic balloon pump. At multivariate
      analysis, extracardiac arteriopathy and New York Heart Association class IV were
      the independent predictors for in-hospital mortality. Neurologic events were
      1.1%. At univariate analysis, significant determinants of neurologic events were
      age, logistic EuroSCORE greater than 15, and extracardiac arteriopathy. At
      multivariate analysis no independent factor for neurologic events was found.
      Survival at 36 months was 95.6% +/- 0.9%, and freedom from cardiac-related events
      at follow-up was 91.6% +/- 1.7%. Linearized rates of cardiac-related events
      during follow-up were as follows: recurrence of angina, 1.1% +/- 0.3%/y;
      myocardial infarction, 0.6% +/- 0.2%/y; congestive heart failure, 1.2% +/-
      0.3%/y; graft occlusion, 0.4% +/- 0.2%/y; and re-coronary artery bypass grafting,
      0.2% +/- 0.1%/y. CONCLUSIONS: Total arterial OPCAB has a safe outcome in terms of
      mortality and neurologic events and has a low linearized rate of cardiac-related
      events at follow-up, even for patients with a moderate- to high-risk profile.

PMID- 15511439
TI  - Off-pump awake coronary revascularization using bilateral internal thoracic
      arteries.
AB  - BACKGROUND: A new technique has been developed that permits complete arterial
      revascularization of the lateral and/or inferior wall of the heart using in situ
      bilateral internal thoracic artery grafts in awake patients. This technique,
      without cardiopulmonary bypass and mechanical ventilation, creates the least
      invasive revascularization method for the lateral and/or posterior wall of the
      heart yet described. METHODS: In 7 patients double or triple vessel coronary
      artery bypass grafting was performed without general anesthesia. A high thoracic
      epidural anesthesia was started one hour before surgery. Bilateral internal
      thoracic arteries were harvested and all anastomoses were performed with the off
      pump technique by standard median sternotomy. Circumflex, or the right coronary
      artery, were anastomosed with bilateral internal thoracic arteries using a heart
      positioner. Six patients received double bypass grafting and one patient received
      triple bypass grafts (bilateral internal thoracic arteries and one radial
      artery). RESULTS: All patients remained awake throughout the whole procedure.
      There was no perioperative myocardial infarction or mortality. Pneumothorax was
      observed in three patients, but it was repaired in two. Only one patient
      completed the procedure with unilateral pneumothorax. There were no hemodynamic
      and pulmonary problems during lateral or posterior wall revascularization. Two
      patients required unexpected coronary endarterectomy during circumflex and right
      coronary artery anastomoses. CONCLUSIONS: Complete arterial revascularization by
      median sternotomy using in situ bilateral internal thoracic artery grafts without
      general anesthesia is a feasible and safe procedure for multivessel disease. This
      approach gives a chance for awake revascularization of the right and/or
      circumflex coronary artery.

PMID- 15511440
TI  - Invited commentary.

PMID- 15511441
TI  - On-pump versus off-pump coronary artery bypass grafting in diabetic patients: a
      propensity score analysis.
AB  - BACKGROUND: Diabetic patients are recognized as being at high risk for adverse
      outcomes after coronary artery bypass grafting. We evaluated our outcomes in
      diabetic patients to compare the effect of off-pump with on-pump coronary
      revascularization. METHODS: Between April 1997 and September 2002, 951
      consecutive diabetic patients underwent isolated coronary artery bypass grafting.
      A total of 186 (19.6%) of these patients had off-pump coronary procedures.
      Multivariate logistic regression was used to assess the effect of off-pump
      coronary procedures on adverse in-hospital outcomes, while adjusting for patient
      and disease characteristics by constructing a propensity score from core patient
      characteristics. The propensity score was the probability of receiving off-pump
      coronary operation, with a C-statistic of 0.81, and was included along with the
      comparison variable in a multivariable analysis of outcome. All analysis was
      performed retrospectively. RESULTS: Off-pump patients were more likely to be
      obese (p = 0.032), have left main stem stenosis (p = 0.034), and have undergone
      prior cardiac operation (p = 0.027). The off-pump group had fewer patients with
      three-vessel disease compared with the on-pump group. After risk adjusting with
      propensity score, off-pump patients had a significantly lower incidence of stroke
      (adjusted odds ratio 0.15; p = 0.039) and renal failure (adjusted odds ratio
      0.38; p = 0.036). Off-pump patients also required less blood transfusion (p <
      0.001) and had shorter lengths of stay (p < 0.001). CONCLUSIONS: Off-pump
      coronary operation in diabetic patients significantly reduced postoperative
      morbidity and length of stay compared with on-pump coronary operation, although
      no in-hospital survival difference was noted between the two groups.

PMID- 15511442
TI  - Surgical reconstruction of the left main coronary artery: fresh autologous
      pericardium or saphenous vein patch.
AB  - BACKGROUND: Isolated stenosis of the left main coronary artery is usually treated
      by coronary bypass surgery. However, this approach restores a less physiologic
      perfusion of the myocardium that leads to occlusion of the left main coronary
      artery, and restores only a retrograde perfusion of a rather extensive myocardial
      area. Coronary ostial plasty has been described as an alternative surgical
      technique in isolated ostial left main coronary artery stenosis without
      calcification. We review our experience with 15 patients. METHODS: After placing
      the patient on cardiopulmonary bypass and aortic cross clamping, the main
      pulmonary trunk was retracted laterally. The left main coronary artery was
      approached anteriorly through a curved aortotomy. Reconstruction was performed
      using fresh pericardial patch or saphenous vein that was tailored as a patch.
      RESULTS: There were no early mortality or perioperative myocardial infarctions.
      During mean follow-up of 55 +/- 39 months, no patients had any cardiac events or
      required repeated coronary intervention. All patients underwent follow-up
      transesophageal echocardiography, which demonstrated a wide open left main
      coronary artery (range 3 to 8 mm), normal flow pattern by pulsed-wave Doppler,
      and no aneurysmal dilatation or calcification of the onlay patch. Coronary
      angiography and intravascular ultrasound were performed in 2 patients because of
      nonspecific chest discomfort. In both cases, the left main coronary artery was
      found to be wide open, and there were no signs of patch calcification.
      CONCLUSIONS: Surgical reconstruction of the left main coronary artery is safe and
      effective for the treatment of selected cases of isolated left main stenosis. The
      use of autologous pericardium appears to be as safe as saphenous vein patch.
      Neither method was associated with postoperative aneurysmal dilatation or
      calcification.

PMID- 15511443
TI  - Histopathology and morphometry of radial artery conduits: basic study and
      clinical application.
AB  - BACKGROUND: The purpose of this study was to determine the pathohistology,
      morphometry, and risk factors for the development of intimal hyperplasia,
      calcification, and arteriosclerosis in the radial artery and to compare the
      morphometry of the distal and proximal radial arteries. METHODS: A total of 190
      proximal and distal radial artery specimens obtained from patients who underwent
      myocardial revascularization were exposed to histopathologic and morphometric
      analysis. The severity of disease was evaluated on the basis of the percentage of
      luminal narrowing, intimal thickness index, and intima-to-media ratio. RESULTS:
      Sixty-two proximal (32.6%) and 22 distal (11.5%) radial artery segments were
      indicated as histologically normal. Morphometric analysis (Z test) revealed a
      lesser degree of intimal hyperplasia and luminal narrowing in the proximal
      segments compared with the distal segments (p < 0.001). The incidence of intimal
      hyperplasia, medial calcification, and arteriosclerosis in the distal radial
      arteries was 76.3%, 6.3%, and 5.78%, respectively. Using multivariate logistic
      regression, we have identified three significant predictors for intimal
      hyperplasia. Expressed as an odds ratio with a 95% confidence interval, these
      included (i) age greater than 50 years (1.052; 1.000-1.106, p = 0.052), (ii)
      smoking (14.073; 5.293-37.414, p = 0.000), and (iii) hypertension (2.777; 1.171
      6.583, p = 0.020). Factors associated with an increased likelihood of medial
      calcification and arteriosclerosis included a history of smoking, diabetes,
      hypercholesterolemia, peripheral arterial disease, and chronic renal failure (p <
      0.05). CONCLUSIONS: The great majority of radial artery conduits indicate
      preexisting intimal hyperplasia mostly affecting the distal portion. Therefore in
      cases of longer diseased segments of radial arteries, the discarded segments
      should be the distal end. Care should be taken when selecting radial artery as a
      conduit in myocardial revascularization, particularly in elderly males,
      diabetics, smokers, hypertensive patients, and in those with associated
      peripheral vascular disease.

PMID- 15511444
TI  - Invited commentary.

PMID- 15511445
TI  - Latent infective endocarditis: epidemiology and clinical characteristics of
      patients with unsuspected endocarditis detected after elective valve replacement.
AB  - BACKGROUND: The diagnosis of infective endocarditis is usually made on the basis
      of clinical and laboratory criteria and may be confirmed by histologic
      examination or culture of excised valves. We tried to determine the incidence and
      significance of inflammatory changes in valves excised during operations for
      reasons other than infective endocarditis. METHODS: The charts and histopathology
      of all patients undergoing valve replacement during a 10-year period (1993-2002)
      were reviewed. A total of 868 patients underwent a total of 970 valve
      replacements during this period, of whom 11 patients (1.3%) were for
      endocarditis, with the remaining 857 (98.7%) for other indications. All excised
      valves were cultured and examined histologically for the presence of inflammatory
      infiltrates, vegetations, and microorganisms. RESULTS: In 8 of 857 patients
      (0.9%), the histologic examination unexpectedly demonstrated an infiltrate
      suggestive of endocarditis. Blood and valve cultures, and serologic tests for
      Mycoplasma, Chlamydia, Legionella, Q fever, Brucella, Rickettsiae, VDRL, and
      Bartonella were negative in all but 1 patient, who was found to have Q fever. All
      received a prolonged course of antibiotics. Six patients had an uneventful
      recovery; 1 had intramyocardial abscesses and expired during cardiac reoperation;
      and 1 had recurrent fever and dehiscence of the aortic and mitral valve
      prostheses and after two cardiac reoperations remains in severe heart failure.
      CONCLUSIONS: The presence of an unexpected inflammatory infiltrate in heart
      valves excised for reasons other than endocarditis may occur in 0.9% of such
      operations; these infiltrates could indicate presence of endocarditis. A
      microbial origin should be sought, and patients should receive empiric antibiotic
      treatment for endocarditis.

PMID- 15511446
TI  - Descending thoracic aortic rupture: role of endovascular stent-grafting.
AB  - BACKGROUND: The mortality of patients with descending thoracic aortic rupture who
      are treated by conventional surgery is high. Our current strategy for the
      management of descending thoracic aortic rupture is to treat seriously ill
      patients with endovascular stent-grafting using handmade grafts, and to treat
      other patients with traditional open repair. The aim of this study was to assess
      the early results of our strategy. METHODS: Twenty-nine consecutive patients with
      descending thoracic aortic rupture were referred to Sapporo Medical University
      Hospital from June 2001 to January 2004. Eighteen of these 29 patients were
      selected for endovascular stent-grafting because of polytrauma (n = 7),
      comorbidities (n = 6), advanced age (n = 2), past history of left thoracotomy (n
      = 2), and patient's preference (n = 1). The remaining 11 patients underwent
      traditional graft replacement of the diseased aorta. Their outcomes and follow-up
      data were collected and analyzed retrospectively. RESULTS: The in-hospital
      mortality rate was 14% (4/29). The mortality rate for surgical patients and stent
      grafting patients was 9% (1/11) and 17% (3/18), respectively. The survival rate
      of patients at 2 years was 63% +/- 10%. In the follow-up period, 2 of the 18
      patients who underwent endovascular stent-grafting required open repair, and 1
      patient underwent a redo endovascular stent-grafting procedure because of stent
      failure. One of these 3 patients died of an intraoperative retrograde type A
      aortic dissection. CONCLUSIONS: The early results of endovascular stent-grafting
      for the treatment of high-risk patients with descending thoracic aortic rupture
      are promising. Early results of open repair can also be improved by the selection
      of stabilized patients. However, the requirement of reintervention indicates that
      detailed follow-up examinations in patients who have undergone endovascular stent
      grafting with handmade stent-grafts should be performed.

PMID- 15511447
TI  - Severity of intraoperative tricuspid regurgitation predicts poor late survival
      following cardiac transplantation.
AB  - BACKGROUND: This study evaluates the significance of tricuspid regurgitation (TR)
      on long-term survival as detected by intraoperative transesophageal
      echocardiography at the time of orthotopic heart transplantation. Although
      significant (2+ to 4+) TR after orthotopic heart transplantation is rare, its
      influence on long-term survival is unknown, warranting further investigation.
      METHODS: Between January 1992 and July 2001, 181 consecutive patients underwent
      orthotopic heart transplantation. Tricuspid regurgitation was graded by
      intraoperative transesophageal echocardiography after final separation from
      cardiopulmonary bypass in 130 of 181 patients (72%). RESULTS: Although 80%
      (104/130) of patients had either no (0, n = 77) or trace (1+, n = 27) TR, 9%
      (12/130 patients) had mild (2+), 10% (13/130 patients) had moderate (3+), and
      0.8% (1/130 patients) had severe (4+) TR. The severity correlated strongly with
      the presence of right ventricular dysfunction (p < 0.001). In a multivariate
      regression model, gender mismatch (p = 0.002) and right ventricular dysfunction
      (p < 0.001) were independent predictors for equal to or greater than mild (2+ to
      4+) TR (p = 0.015). Although the degree of recipient pulmonary vascular
      resistance did not influence the grade (p = 0.600), higher pulmonary vascular
      resistance tended to increase the severity of TR in the setting of prolonged
      donor ischemic times (p = 0.054). Proportional hazards regression analysis
      demonstrated significantly decreased survival for patients with mild or greater
      (2+ to 4+) TR detected by transesophageal echocardiography at the time of
      transplantation (p < 0.001) and RV dysfunction (p = 0.023). CONCLUSIONS: Even
      mild (> or = 2+) TR identified by transesophageal echocardiography at the time of
      orthotopic heart transplant predicts poor late survival, suggesting a possible
      role for concomitant tricuspid valve repair at the time of transplant. Whether or
      not tricuspid valve repair will improve long-term survival is unknown.

PMID- 15511448
TI  - Invited commentary.

PMID- 15511449
TI  - Extracorporeal membrane oxygenation is superior to right ventricular assist
      device for acute right ventricular failure after heart transplantation.
AB  - BACKGROUND: Acute right ventricular failure after heart transplantation is a life
      threatening condition, and sometimes the use of mechanical circulatory support is
      inevitable. The aim of this retrospective study was to investigate the
      effectiveness of two different mechanical circulatory support systems for this
      indication. METHODS: From 1984 to 2003, 28 heart transplant recipients exhibited
      right ventricular failure resistant to drug therapy. Right ventricular assist
      device (n = 15) or extracorporeal membrane oxygenation (n = 13) was implanted to
      support the failing heart. RESULTS: Overall in-hospital survival was 43%. In the
      right ventricular assist device group, only 2 patients (13%) could be weaned from
      mechanical circulatory support compared with 10 patients (77%) in the
      extracorporeal membrane oxygenation group (p = 0.001). Retransplantation was
      necessary in 6 patients in the right ventricular assist device group and in 1
      patient in the extracorporeal membrane oxygenation group (p = 0.049). There was
      no difference in patient survival between groups, but graft survival was
      significantly better in the extracorporeal membrane oxygenation group (p =
      0.005). CONCLUSIONS: In view of these results, extracorporeal membrane
      oxygenation seems to be the better option as mechanical circulatory support for
      right ventricular failure in heart transplantation.

PMID- 15511450
TI  - Glucose-insulin-potassium in cardiac surgery: a meta-analysis.
AB  - BACKGROUND: Glucose-insulin-potassium therapy (GIK) has been suggested to reduce
      mortality and improve postoperative recovery after cardiac surgery. We performed
      a meta-analysis of all randomized studies using GIK in cardiac surgery. METHODS:
      A systematic Medline search for all GIK studies in cardiac surgery was carried
      out. Randomized studies investigating the recovery of contractile function as a
      primary endpoint were included in the meta-analysis. RESULTS: Thirty-five GIK
      trials were identified. Twenty-four studies were excluded because of lack of
      randomization, supplementary administration of other substances, or due to other
      primary endpoints. Eleven studies were included with a total of 468 patients who
      underwent either coronary artery bypass grafting or heart valve replacement. Six
      studies noted a significant improvement in postoperative recovery. One study
      demonstrated no effect. In four studies, no comparable statistical analysis was
      available. GIK patients required similar or lesser doses of catecholamines. From
      the available data we estimated a weighted mean of relative improvement in
      postoperative recovery of cardiac index for GIK patients versus controls of
      11.4%. Five of 11 studies reported the incidence of postoperative atrial
      fibrillation (AF). AF occurred in 23% (20/86) in GIK versus 42% (36/86) in
      control patients (p = 0.009). CONCLUSIONS: The findings indicate that GIK may
      considerably improve postoperative recovery of contractile function and reduce
      the incidence of atrial arrhythmias after cardiac surgery. However, several
      factors limit the power of this analysis and large, randomized multicenter trials
      are needed to fully assess the efficacy of GIK after cardiac surgery.

PMID- 15511451
TI  - Invited commentary.

PMID- 15511452
TI  - Sternal preservation: a better way to treat most sternal wound complications
      after cardiac surgery.
AB  - BACKGROUND: Postcardiotomy sternal wound complications remain challenging. The
      prevailing approach for deep sternal wound infection of debridement and flap
      coverage without osseous closure makes subsequent reoperation difficult. METHODS:
      An analysis of all patients undergoing cardiac surgery at a single institution
      between 1986 and 2001 was conducted. Prospective data collection and chart review
      were used to compare different treatment strategies for sternal complications.
      RESULTS: Of 5337 patients, 122 had sternal wound complications (2.2%) comprising
      15 (0.3%) uninfected dehiscences (El Oakley class 1), 45 (0.8%) superficial
      infections (El Oakley class 2A), and 62 (1.1%) deep sternal wound infections (El
      Oakley class 2B). Thirty-two patients with deep sternal infection were treated by
      debridement, rewiring, and delayed primary closure. There were initial treatment
      failures in 6 patients (18.8%) and ultimate failures in 2 patients (6.3%), both
      of whom died. One of these patients had previously received external beam
      radiation after a radical mastectomy for breast cancer. Median length of stay was
      32 days and median time to wound healing was 85 days. Twenty-five patients were
      managed by muscle flap coverage without sternal reclosure. There were 6 initial
      treatment failures (24%) but no ultimate failures or deaths (p = NS). Median
      length of stay was 31 days and median infection time was 161 days. CONCLUSIONS:
      In patients with postcardiotomy deep sternal wound infection without previous
      chest radiation, debridement, rewiring, and delayed skin closure is effective. It
      offers a shorter healing time and probably makes late cardiac reoperation safer.
      We propose an algorithm for the management of poststernotomy complications.

PMID- 15511453
TI  - A prospective multicenter trial of bipolar radiofrequency ablation for atrial
      fibrillation: early results.
AB  - BACKGROUND: The Cox-Maze III remains the gold standard for the surgical treatment
      of atrial fibrillation. However, the "cut-and-sew" technique is time consuming
      and technically challenging. The pulmonary veins are the source of ectopy in the
      majority of patients with atrial fibrillation. The safety and efficacy of bipolar
      radiofrequency to electrically isolate the pulmonary veins was evaluated in a
      prospective multi-center trial. METHODS: Beginning in January 2002, 30 patients
      at three medical centers underwent pulmonary vein isolation using bipolar
      radiofrequency and were followed for 6 months. Twenty-four of the patients also
      underwent a modified Cox-Maze III. Electrical isolation of the pulmonary veins
      was confirmed with intraoperative pacing. Pulmonary vein patency was assessed by
      magnetic resonance imaging or three-dimensional computed tomography in 15
      patients at 1 month. RESULTS: Mean age was 60.9 +/- 11.7 years. Nineteen patients
      had paroxysmal atrial fibrillation. All pulmonary veins were isolated in every
      patient. The left pulmonary veins underwent 3.0 +/- 1.4 applications for a total
      of 26.4 +/- 10.5 seconds. The right pulmonary veins underwent 2.8 +/- 1.1
      applications for a total of 26.3 +/- 12.6 seconds. There was no operative
      mortality. At 1 month, imaging revealed no evidence of pulmonary vein stenosis.
      At 6 months, 96% of patients were in normal sinus rhythm. CONCLUSIONS: The use of
      bipolar radiofrequency for electrical isolation of pulmonary veins and to replace
      other Cox-Maze III incisions is safe and effective at controlling atrial
      fibrillation. This emerging technology may shorten and simplify the surgical
      management of atrial fibrillation.

PMID- 15511454
TI  - Successful performance of Cox-Maze procedure on beating heart using bipolar
      radiofrequency ablation: a feasibility study in animals.
AB  - BACKGROUND: The Cox-Maze procedure is the gold standard for the surgical
      treatment of atrial fibrillation with proven long-term efficacy. However, its
      application has been limited by its complexity and significant morbidity. The
      purpose of this study was to test the feasibility and safety of performing the
      Cox-Maze procedure using bipolar radiofrequency ablation on the beating heart
      without cardiopulmonary bypass. METHODS: After median sternotomy, 6 Hanford mini
      pigs underwent a modified Cox-Maze procedure using bipolar radiofrequency energy.
      The animals survived for 30 days. Atrial function, coronary artery, pulmonary
      vein anatomy, and valve function were assessed by magnetic resonance imaging. At
      reoperation, pacing documented electrical isolation of the pulmonary veins.
      Induction of atrial fibrillation was attempted by burst pacing with cholinergic
      stimulation. Histologic assessment was performed after sacrifice. RESULTS: There
      were no perioperative mortalities or neurologic events. At 30 days, atrial
      fibrillation was unable to be induced, and pulmonary vein isolation was confirmed
      by pacing. Magnetic resonance imaging assessment revealed no coronary artery or
      pulmonary vein stenoses. Although atrial ejection fraction decreased slightly
      from 0.344 +/- 0.0114 to 0.300 +/- 0.055 (p = 0.18), atrial contractility was
      preserved in every animal. Histologic assessment showed all lesions to be
      transmural, and there were no significant stenoses of the coronary vessels or
      injuries to the valves. CONCLUSIONS: Virtually all of the lesions of the Cox-Maze
      procedure can be performed without cardiopulmonary bypass using bipolar
      radiofrequency energy. There were no late stenoses of the pulmonary veins.
      Clinical trials of this new technology on the beating heart are warranted.

PMID- 15511455
TI  - Ventricular resynchronization by multisite pacing improves myocardial performance
      in the postoperative single-ventricle patient.
AB  - BACKGROUND: Ventricular resynchronization with multisite pacing in heart failure
      patients results in acute improvement of myocardial performance, but the
      mechanism is unknown. Our goals were to determine whether multisite pacing
      results in acute improvement of myocardial performance in postoperative single
      ventricle patients, and to elucidate the mechanism by assessing the
      synchronization of regional ventricular contraction during multisite pacing using
      real-time three-dimensional echocardiographic imaging. METHODS: Multisite pacing
      studies were performed in 26 single-ventricle patients (mean age, 28 months;
      range, 7 days to 11 years) undergoing some form of single-ventricle palliation
      (stage I Norwood, 4; aortopulmonary shunt, 1; cavopulmonary shunt, 9; Fontan, 8;
      Fontan revision, 3; valve replacement, 1). Electrocardiogram, blood pressure,
      mixed-venous oxygen saturation, and three-dimensional echocardiograms (n = 10)
      were recorded at baseline and during multisite pacing. Data were analyzed to
      obtain regional volume-time curves for 16 three-dimensional segments of the
      systemic ventricle. An index of asynchrony was calculated at baseline and during
      pacing as the standard deviation of all segmental volume-time curves from onset
      to end of ejection. RESULTS: With multisite pacing performed at a median
      postoperative day 2 (range, 0 to 9), QRS duration decreased in 24 of 26 patients
      (93.9 +/- 17.5 versus 71.7 +/- 10.8 ms; p < 0.001); systolic blood pressure
      increased in 25 of 26 patients (86.3 +/- 20.0 versus 93.8 +/- 20.2 mm Hg; p <
      0.001); cardiac index increased in 21 of 22 patients (3.2 +/- 0.8 versus 3.7 +/-
      1.0 L x min(-1) x m(-2); p < 0.001); and the index of asynchrony improved in 8 of
      10 patients (10.3 +/- 4.8 versus 6.0 +/- 1.4; p < 0.04). CONCLUSIONS: Multisite
      pacing improves cardiac performance after single-ventricle palliation. Real-time
      three-dimensional echocardiography demonstrated that multisite pacing improved
      the synchrony of ventricular contraction.

PMID- 15511456
TI  - Postpericardiotomy syndrome after permanent pacemaker implantation in children
      and young adults.
AB  - BACKGROUND: Postpericardiotomy syndrome (PPS) occurs in 10% to 50% of pediatric
      patients after cardiac surgery. The incidence and outcome of PPS after permanent
      pacemaker implantation in children is not described. METHODS: A retrospective
      analysis was performed of all pediatric patients who underwent isolated placement
      of a pacemaker between January 1984 and December 2002. Patients who underwent
      congenital heart surgery at the time of pacemaker implantation were excluded. PPS
      was diagnosed on the basis of clinical symptoms with echocardiographic
      confirmation of a pericardial effusion. RESULTS: Four hundred and forty-three
      pacemakers (237 epicardial, 206 transvenous) were implanted in 370 patients
      (median age 10 years, range 2 months to 24 years). Eight (2%) episodes of PPS (6
      epicardial, 2 transvenous) occurred in 7 patients. The median time from
      implantation to PPS was 12.5 days (range 8 to 22 days). Six (75%) episodes
      followed primary pacemaker implantation, two occurred after subsequent lead
      revision. Three patients were initially treated with medical therapy (1
      nonsteroidal agents, 2 steroids), and 1 required subsequent pericardiocentesis.
      Five patients underwent initial pericardiocentesis followed by medication. One
      patient had echocardiographic recurrence of a pericardial effusion 3 weeks after
      a nonsteroidal taper, with resolution after nonsteroidal agents were reinitiated.
      One patient required a pericardial window for a persistent effusion. No pacemaker
      was explanted. CONCLUSIONS: PPS occurred in 2% of children undergoing isolated
      pacemaker implantation of both epicardial and transvenous systems. PPS is usually
      managed successfully with medical therapy. Patients with medical treatment
      failure were successfully treated with pericardiocentesis or the surgical
      creation of a pericardial window.

PMID- 15511457
TI  - Improving outcomes in functional single ventricle and total anomalous pulmonary
      venous connection.
AB  - BACKGROUND: We have previously reported that the outcome of infants with
      functional single ventricle and total anomalous pulmonary venous connection is
      poor relative to that of other single ventricle patients. Younger age at initial
      operation and obstructed total anomalous pulmonary venous connection were found
      to be risk factors for mortality. A review of our recent experience was
      undertaken to determine whether results in these patients are improving. METHODS:
      Medical records of 18 patients admitted after 1997 were reviewed (group B) and
      compared with the previous group of 73 patients admitted between 1984 and 1997
      (group A). Data were analyzed using a Cox proportional hazards model. RESULTS:
      Median age at first operation was the same for both groups. The incidence of
      obstructed total anomalous pulmonary venous connection was not significantly
      different between groups (29% versus 33%, p = 0.70). Early survival is
      significantly improved for group B compared with group A (p = 0.015). Only group
      and younger age at initial operation were found to be risk factors for mortality.
      In the current group, 5 patients have undergone superior cavopulmonary connection
      with one death, 3 have undergone Fontan completion with no deaths, and heart or
      heart-lung transplantation was performed in 5 patients with two deaths.
      CONCLUSIONS: Early survival in patients with single ventricle and total anomalous
      pulmonary venous connection has improved significantly in recent years, but
      intermediate survival is still approximately 50%. Selective management using
      staged reconstructive surgery and transplantation may result in improved
      survival. Further study may identify risk factors for mortality and improve
      selection of appropriate patients for each therapy.

PMID- 15511458
TI  - Associated factors and trends in outcomes of interrupted aortic arch.
AB  - BACKGROUND: Interrupted aortic arch (IAA) continues to be associated with
      important mortality, both before and immediately after repair, with ongoing
      morbidity during follow-up. We sought to determine trends in presentation,
      management, outcomes and associated factors. METHODS: We reviewed all consecutive
      patients (n = 119) presenting from 1975 to 1999, and data were collected
      regarding demographics, anatomy, management and outcomes. RESULTS: Significant
      trends over time for patients born in three consecutive periods (1975 to 1984,
      1985 to 1993, and 1994 to 1999) demonstrated a smaller proportion of patients
      with presentation with circulatory collapse (65%, 51%, and 25%, respectively),
      greater use of prostaglandins (72%, 90%, 100%), fewer deaths without IAA repair
      (49%, 15%, 13%) and greater use of one-stage repair (68%, 75%, 100%). Independent
      risk factors for death without IAA repair (p < 0.001) included absence of
      ventricular septal defect, and the presence of noncardiac anomaly, complex
      cardiac anomaly, episode of acidosis and earlier birth cohort. Overall survival
      after repair was 50% at age 1 month, 35% at 1 year, and 34% at 5 years. Early and
      constant-hazard phases were noted, with incremental risk factors for early phase
      mortality being cyanosis at presentation, presence of truncus arteriosus or
      aortic stenosis, an episode of circulatory collapse before repair, earlier date
      of repair, and lower weight at repair. Greatest survival occurred in those
      patients with uncomplicated IAA who had repair since 1993 (5 year survival, 83%).
      Freedom from reintervention for arch obstruction was 60% at 5 years. CONCLUSIONS:
      While improving, outcomes of IAA remain of concern, especially in patients with
      associated lesions.

PMID- 15511459
TI  - Pediatric cardiac transplantation in children with high panel reactive antibody.
AB  - BACKGROUND: Elevated panel reactive antibody (PRA) may be considered a risk
      factor precluding pediatric orthotopic heart transplantation. We retrospectively
      reviewed our management strategy and outcome data for children undergoing heart
      transplantation with high PRA (> 10%). METHODS: Sixty consecutive children
      (median age = 130.5 days) underwent heart transplantation. Diagnoses included
      hypoplastic left heart syndrome (HLHS) (30 patients), cardiomyopathy (18
      patients), and postoperative complex congenital heart disease (CCHD) (12
      patients). Standard induction immunosuppressive therapy included pulse steroids,
      gamma globulin, and polyclonal rabbit antithymocyte globulin. Initial
      immunosuppression is a calcinurin inhibitor and an antiproliferative agent. Eight
      children exhibited elevated PRA (group P). Fifty-two exhibited nonelevated PRA
      (group N). Immunosuppression was modified in group P as follows: preoperative
      intravenous immunoglobulin G (IVIG) and/or cyclophosphamide or mycophenolate
      mofetil and preoperative and postoperative exchange transfusions or
      plasmapheresis. In group P, cyclophosphamide was the initial antiproliferative
      agent. RESULTS: Group P = 4 HLHS patients (all status post [s/p] prior cardiac
      surgery) and 4 postoperative CCHD patients. Group N = 26 HLHS patients (4
      patients s/p prior cardiac surgery), 18 cardiomyopathy patients, and 8
      postoperative CCHD patients. Group P patients were older and weighed more than
      group N patients. Waiting time for donor heart, cardiac ischemic time, and length
      of hospital stay were similar in both groups. Thirty-day mortality for group P
      was 25% and for group N it was 7.9% (p = 0.178). Overall mortality for group P
      was 50% and for group N it was 15.4% (p = 0.043). CONCLUSIONS: Although heart
      transplantation can offer children with end-stage heart failure and elevated PRA
      their only chance of survival, these patients remain high risk despite aggressive
      immunosuppression.

PMID- 15511460
TI  - Basal metabolic state of hearts of patients with congenital heart disease: the
      effects of cyanosis, age, and pathology.
AB  - BACKGROUND: Experimental models have established numerous myocardial metabolic
      changes with chronic hypoxia and maturation. We conducted this study to
      specifically look at the effects of cyanosis, age, and pathology upon the basal
      metabolic state of the immature human heart. METHODS: One hundred and eighty-one
      pediatric patients (37 cyanotic, 144 acyanotic) undergoing open heart surgery
      were recruited. A myocardial biopsy was collected before ischemia and analyzed
      for adenine nucleotides, purines, and lactate. The effect of cyanosis was
      estimated by an analysis of age-matched pairs of children with either ventricular
      septal defects or tetralogy of Fallot, and by multiple regression modeling. The
      effects of age and pathology were estimated in acyanotic children also by
      multiple regression modeling (adjustments were made for baseline differences).
      RESULTS: The only effect of cyanosis was for lactate where the paired t test, and
      unadjusted and adjusted regression analyses were all consistent (ranging from
      1.33 to 1.48 times higher in cyanotic than acyanotic children). The
      concentrations of adenosine triphosphate (ATP), adenosine diphosphate (ADP), and
      adenosine monophosphate (AMP) declined with age, whereas the ATP/ADP ratio
      increased; these associations remained significant even in the adjusted
      regression analysis. None of the effects of acyanotic pathology were highly
      significant (p < 0.01), implying that few important metabolic differences were
      attributable to pathology. CONCLUSIONS: Cyanosis and age are important factors
      that determine the basal metabolic state of the pediatric heart. Cyanotic
      patients have higher myocardial lactate concentrations, whereas young age is
      associated with lower ATP/ADP ratios and higher adenine nucleotide levels.

PMID- 15511461
TI  - Open heart surgery for small children without homologous blood transfusion by
      using remote pump head system.
AB  - BACKGROUND: To avoid excessive hemodilution, the transfusion of a large amount of
      homologous blood may be required in open heart surgery for small children, which
      in turn, can cause a significant immunologic response. METHODS: Cardiopulmonary
      bypass systems with remote pump heads were used for patients weighing 5 kg or
      less that were undergoing ventricular septal defect repair. The procedures took
      place from January 1997 to August 2002. The surgery was started with bloodless
      prime in 122 out of 158 (77.2%) consecutive patients. Exclusion criteria were a
      predicted hematocrit after the initiation of bypass of less than 15%, respiratory
      failure or heart failure (or both), and pulmonary vascular obstructive disease.
      RESULTS: The mean age and body weight were 3.8 +/- 1.8 months and 4.3 +/- 0.5 kg,
      respectively. The priming volume was 181.0 +/- 32.5 (minimum: 130) mL. The
      hematocrit after cardiopulmonary bypass was initiated was 16.7% +/- 2.3%. Six
      patients required subsequent blood transfusion owing to postoperative
      complications that resulted in compromised hematopoiesis. In the rest, the
      hematocrit before discharge was 30.6% +/- 3.0%. Renal and liver function tests
      were maintained within the normal range. Patients were extubated at 5.6 +/- 2.8
      hours after operation with proper oxygenation. Neurodevelopment was apparently
      normal. The Japanese psychomotor developmental scale assessment was given to
      patients without chromosomal abnormality between the ages of 1 and 3 years; the
      resulting score was 102.2 +/- 15.4 (mean = 100 for normal population).
      CONCLUSIONS: Open heart surgery was achieved without blood transfusion in the
      selected group of small children. The use of remote pump heads reduced the
      overall need for blood transfusions and possibly inflammatory reactions.

PMID- 15511462
TI  - Venovenous extracorporeal membrane oxygenation for cyanotic congenital heart
      disease.
AB  - BACKGROUND: Severe, refractory hypoxemia complicating uncorrected cyanotic
      congenital heart disease is a potentially lethal condition, even when urgent
      surgical intervention is undertaken. When a viral pneumonia initiates hypoxemia,
      the likelihood of a satisfactory outcome is further reduced. We examined our
      policy of venovenous extracorporeal membrane oxygenation support through the
      hypoxic event and performing delayed surgery, if required, to separate from
      extracorporeal membrane oxygenation. METHODS: A single institution, retrospective
      review of an Institutional Review Board approved database was undertaken. Over a
      6-year period, 18 instances were identified for 17 patients who became acutely
      hypoxemic from either inadequate pulmonary blood flow (8 instances) or a viral
      pneumonia (10 instances) complicating their cyanotic heart disease. Demographics,
      duration of venovenous extracorporeal membrane oxygenation and outcomes are
      reported. RESULTS: The length of venovenous extracorporeal membrane oxygenation
      ranged from 13.5 to 362.5 hours (mean 130 +/- 121 hours). During 10 supports,
      operations were performed to facilitate weaning from support. In 7 patients,
      extracorporeal support was weaned during this surgery. Follow-up was obtained in
      all patients over a period ranging from 4 months to 7 years (mean 39.0 +/- 23.0
      months). There were two late deaths due to sepsis 1.4 and 2.5 months after
      extracorporeal support. CONCLUSIONS: Venovenous extracorporeal membrane
      oxygenation allows time for the recovery of acute hypoxic insult and resolution
      of some viral pneumonia processes. Palliative surgical procedures may be safely
      undertaken during extracorporeal support. Viral pneumonia is a risk for prolonged
      support. Venovenous extracorporeal membrane oxygenation is useful in these high
      risk patients.

PMID- 15511463
TI  - Bronchioloalveolar carcinoma of the lung 3 centimeters or less in diameter: a
      prognostic assessment.
AB  - BACKGROUND: Bronchioloalveolar carcinoma (BAC) of the lung is a subtype of
      adenocarcinoma for which the incidence is actually rising, but the histologic
      definition of BAC has been recently changed by the revised World Health
      Organization (WHO) classification in 1999. The clinical features of patients with
      BAC diagnosed according to the recently revised WHO classification have not yet
      been clarified. In this retrospective study, we investigated the pattern of
      recurrence and survival outcome for patients with resected BAC by pathology
      review, compared with those in patients who had adenocarcinoma other than BAC.
      METHODS: From 1985 through 2002, 108 patients underwent surgical resection for
      pulmonary adenocarcinoma 3 cm or less in diameter at the University of Yamanashi,
      Japan. All of the resected specimens of these 108 patients were pathologically
      reviewed again to confirm the diagnosis as BAC or adenocarcinoma other than BAC.
      The tumor was defined as BAC when the adenocarcinoma lesion had a pure
      bronchioloalveolar growth pattern and no evidence of stromal, vascular, or
      pleural invasion according to the WHO classification (third edition). RESULTS:
      Twenty-five patients (23%) had a diagnosis of BAC, and 83 (77%) had a diagnosis
      of other adenocarcinoma. There was a female predominance among both patients with
      BAC and those with other adenocarcinoma. Lymph node involvement was seen for 30
      lesions (36%) of adenocarcinoma other than BAC, but not for any BAC lesions. The
      median duration of follow-up after surgery was 5.1 years. There was no recurrence
      in the postoperative course in patients with BAC for a 5-year disease-free
      survival rate of 100%, whereas the 5-year disease-free survival rate for other
      adenocarcinoma was 63.5%. CONCLUSIONS: The patients with resected BAC, which is
      defined as a noninvasive adenocarcinoma by the revised WHO classification, had an
      excellent prognosis. However, these results may depend on a strictly accurate
      pathology diagnosis as BAC. Limited resection might be curative in patients with
      focal BAC based on evidence of pathologic noninvasive features.

PMID- 15511464
TI  - SCCRO expression correlates with invasive progression in bronchioloalveolar
      carcinoma.
AB  - BACKGROUND: Overexpression of squamous cell carcinoma-related oncogene (SCCRO) is
      associated with invasive progression and poor outcomes in non-small cell lung
      cancer. We assessed the role of SCCRO as a tumor marker in bronchioloalveolar
      carcinoma (BAC), a subtype of adenocarcinoma exhibiting evidence of histologic
      tumor progression. We hypothesized that SCCRO expression would correlate with
      invasive tumor phenotypes and worse survival in BAC. METHODS: We classified 150
      tumors as pure BAC, BAC with focal invasion, or adenocarcinoma with BAC features.
      A tissue microarray was constructed from areas of benign lung, BAC, and invasive
      adenocarcinoma in these tumors. Squamous cell carcinoma-related oncogene
      expression was graded by immunohistochemistry from 0 to 3 (absent, low, moderate,
      or high), with positive SCCRO phenotype defined as grade 3. Squamous cell
      carcinoma-related oncogene specificity was determined by Wilcoxon rank test and
      area under the receiver-operator curve, survival by the Kaplan-Meier method, and
      correlation with prognostic factors by log-rank test. RESULTS: Of the 86.0% (129
      of 150) of specimens suitable for analysis, positive SCCRO phenotype was seen in
      16.3% (21 of 129) and was 100.0% specific for tumor versus benign tissue (area
      under receiver-operator curve, 0.92). Positive SCCRO phenotype was greater in
      tumors with increasing degrees of invasive histologic type (7.0% pure BAC, 13.6%
      BAC with focal invasion, and 28.6% adenocarcinoma with BAC features; p = 0.02).
      Low-level SCCRO expression was present in 83.9% (99 of 118) of benign tissues and
      correlated with tobacco use and poor survival (p = 0.05). CONCLUSIONS: Squamous
      cell carcinoma-related oncogene is a marker of invasive tumor progression in BAC.
      Low-level expression in adjacent benign lung predicts worse survival, and may
      represent field cancerization or host-tumor effects.

PMID- 15511465
TI  - Personal experience in surgical management of pulmonary pleomorphic carcinoma.
AB  - BACKGROUND: Pleomorphic carcinoma is a rare epithelial malignant tumor. Pulmonary
      pleomorphic carcinoma was introduced by the 1999 World Health Organization
      classification as a new peculiar type of lung carcinoma showing concurrent
      malignant epithelial and sarcomatoid spindle cell elements. Few reports describe
      its clinical behavior. My colleagues and I report a series of patients surgically
      treated for pulmonary pleomorphic carcinoma to describe our experience with this
      malignant neoplasm. METHODS: Twenty cases of pleomorphic pulmonary carcinoma were
      collected and studied clinicopathologically. All patients underwent surgical
      resection. The cases were as follows: 6 stage I, 12 stage II, and 2 stage IIIA.
      Histologic diagnosis was established by using light microscopic examination and
      immunohistochemistry. Survival rates were calculated with the Kaplan-Meier
      method. RESULTS: We postoperatively diagnosed 20 cases of pleomorphic carcinoma:
      14 cases were exclusively spindle and giant-cell carcinomas, 2 cases were spindle
      and giant-cell carcinoma combined with adenocarcinoma, 2 were combined with
      squamous cell carcinoma, and 2 were combined with large cell carcinoma. At last
      follow-up, 4 patients were still alive; they were postoperative T1 N0 and T2 N0.
      The remaining 16 patients died from early distant metastases. The median duration
      of disease-free survival was 5 months. The median duration of overall survival
      was 8 months. CONCLUSIONS: The prognosis of patients with pleomorphic carcinoma
      was poor, despite surgery and adjuvant chemotherapy, because of early relapse of
      disease. Nodal involvement was a determinant prognostic variable, because
      advanced stages were related to worse prognosis. In case of preoperatively proven
      pulmonary pleomorphic carcinoma, surgery should be recommended to N0 patients.

PMID- 15511466
TI  - Arterial invasion predicts early mortality in stage I non-small cell lung cancer.
AB  - BACKGROUND: A retrospective study was performed to evaluate the association
      between arterial invasion and survival in patients with stage I non-small cell
      lung cancer. METHODS: One hundred patients were identified who had undergone
      complete anatomic resection as definitive treatment for stage I non-small cell
      lung cancer. The tumors were reviewed for the presence or absence of arterial
      invasion. Five-year survival data were obtained for all patients. RESULTS: The
      100 patients had an overall 5-year survival of 61%. There were 64 stage IA
      patients with a 62% 5-year survival and 36 stage IB patients with a 58% 5-year
      survival. The 39 patients identified with arterial invasion had a 38% 5-year
      survival compared with a 73% 5-year survival in the 61 patients without arterial
      invasion (p < 0.001), with an unadjusted hazard ratio of 3.5 (p < 0.001).
      Multivariate analysis by stage IA versus IB and by size greater or less than 2 cm
      demonstrated hazard ratios of 3.5 and 4.0, respectively (p < 0.001). This
      difference was independent of demographic characteristics, tumor type, or grade.
      Subgroup analysis revealed a hazard ratio of 5.8 in patients with stage IA non
      small cell lung cancer (p < 0.001) and 19.8 in patients with tumors < or = 2 cm
      (p = 0.006). CONCLUSIONS: Arterial invasion is present in a substantial
      percentage of patients with stage I non-small cell lung cancer and is adversely
      associated with survival.

PMID- 15511467
TI  - Invited commentary.

PMID- 15511468
TI  - Frozen section diagnoses of small pulmonary nodules: accuracy and clinical
      implications.
AB  - BACKGROUND: Pulmonary nodules are frequently first diagnosed by frozen section,
      immediately followed by lobectomy or other procedures. The frozen section
      diagnosis of pulmonary nodules can be difficult, as inflammatory and fibrotic
      lesions can be confused for malignancy, creating intraoperative dilemmas for
      pathologists and thoracic surgeons. METHODS: We reviewed our experience at Cedars
      Sinai Medical Center with the frozen section diagnoses of 183 consecutive
      pulmonary nodules smaller than 1.5 cm in diameter and calculated the sensitivity,
      specificity, and predictive values of this diagnostic procedure. RESULTS: One
      hundred and seventy four nodules were correctly classified by frozen section as
      neoplastic or nonneoplastic, six lesions were diagnosed equivocally, and two
      neoplasms were missed owing to sampling errors. The equivocal frozen section
      diagnoses included two bronchioloalveolar carcinomas (BAC) interpreted as
      "atypical hyperplasia, favor BAC," two BAC diagnosed as "alveolar hyperplasia,"
      and two carcinoid tumors labeled as "atypical carcinoma" and "spindle cell
      lesion, carcinoid versus sclerosing hemangioma," respectively. The sensitivities
      for a diagnosis of neoplasia were 86.9% and 94.1% for nodules smaller than 1.1 cm
      in diameter and measuring 1.1 to 1.5 cm, respectively. The diagnostic accuracy of
      frozen sections was significantly better in nodules larger than 1.0 cm in
      diameter (p = 0.05). There were no false-positive diagnoses of malignancy,
      resulting in 100% specificity. CONCLUSIONS: Intraoperative consultation with
      frozen section is a sensitive and specific procedure for the diagnosis of
      malignancy from small pulmonary nodules. The distinction between BAC and atypical
      adenomatous hyperplasia, and of small peripheral carcinoid tumors from other
      lesions, can be difficult by frozen section. Thoracic surgeons need to become
      aware of these problems and develop appropriate therapeutic strategies.

PMID- 15511469
TI  - Invited commentary.

PMID- 15511470
TI  - Feasibility and results of awake thoracoscopic resection of solitary pulmonary
      nodules.
AB  - BACKGROUND: General anesthesia with single-lung ventilation is considered
      mandatory for thoracoscopic pulmonary resection. We assessed in a randomized
      study the feasibility and results of awake thoracoscopic resection of solitary
      pulmonary nodules. METHODS: Between March 2001 and February 2003, 60 patients
      were randomized into two 30-patients arms: a general anesthesia arm entailing
      double-lumen intubation and thoracic epidural anesthesia (control group); and an
      awake arm entailing sole thoracic epidural anesthesia at T4-T5 (awake group).
      Anesthesia time; operative time; global operating room time; patient satisfaction
      with the anesthesia and technical feasibility scored into 4 grades (from 1 = poor
      to 4 = excellent); visual analog pain score (VAS), nursing care (number of
      patient calls per day), 24 hours changes in arterial oxygenation (DeltaPaO2), and
      hospital stay were assessed. RESULTS: There was no mortality. There was no
      difference in technical feasibility between the groups although 2 patients in the
      awake group required conversion to thoracotomy due to severe adhesions. Other 2
      patients in each group required conversion due to unexpected lung cancer
      requiring lobectomy. Comparisons of awake versus control group results showed
      that in the awake group, anesthesia satisfaction score was greater (4 vs 3, p =
      0.04), whereas DeltaPaO2 (-3 mm Hg vs -6.5 mm Hg, p = 0.002); nursing care (2.5
      calls per day vs 4 calls per day, p = 0.0001), and hospital stay (2 days vs 3
      days, p = 0.02) were significantly reduced. CONCLUSIONS: In our study, awake
      thoracoscopic resection of solitary pulmonary nodules proved safely feasible. It
      resulted in better patient satisfaction, less nursing care and shorter in
      hospital stay than procedures performed under general anesthesia.

PMID- 15511471
TI  - Intrapleural hyperthermic perfusion with chemotherapy increases apoptosis in
      malignant pleuritis.
AB  - BACKGROUND: Previously, we reported on the effectiveness of intrapleural
      hyperthermic perfusion with chemotherapy, a new treatment we developed for
      patients with malignant pleuritis. The present study analyzes the mechanism of
      the effectiveness of this therapy by examining the induction ratio of apoptosis
      among tumor cells following the perfusion treatment. METHODS: This study included
      11 consecutive patients with primary pulmonary adenocarcinoma and accompanying
      pleural seedlings and pleural effusions containing tumor cells but without
      distant metastasis. All patients underwent surgical resection of the primary
      lesion and then received sequential perfusion treatment. Tumor cells collected
      from the effusion both before and again at 24 hours following the perfusion
      treatment were subsequently examined using an immunocytochemical stain to
      determine apoptosis among tumor cells. The percentage of positively stained cells
      was expressed as the apoptotic index. We compared the survival rate of these 11
      patients with the survival rate of a second group of 11 patients with malignant
      pleuritis who underwent surgical resection of the primary lesion but who did not
      receive the perfusion treatment (control group). RESULTS: The ratio of
      spontaneous apoptosis of untreated tumor cells was 2.8% +/- 2.0%. Following the
      perfusion, apoptosis among tumor cells was 25.2% +/- 4.6%, clearly a significant
      increase. While the median survival time for patients receiving the perfusion
      treatment was 20 months, the median survival time for the control group was 6
      months. CONCLUSIONS: In patients with malignant pleuritis, intrapleural
      hyperthermic perfusion with chemotherapy induced potent apoptosis of tumor cells
      in the pleural cavity and also improved the survival rate of these patients as
      compared with patients who did not receive the perfusion treatment.

PMID- 15511472
TI  - Invited commentary.

PMID- 15511473
TI  - Pleural biopsy: a reliable method for determining the diagnosis but not subtype
      in mesothelioma.
AB  - BACKGROUND: Survival after tri-modality therapy with extrapleural pneumonectomy
      (EPP) and postoperative chemoradiotherapy is longer for patients with epithelial
      MPM versus mixed or sarcomatoid subtypes, leading some to decline aggressive
      therapy for patients with nonepithelial histology. However, pathologic diagnosis
      of malignant pleural mesothelioma (MPM) and subclassification into one of the
      three histologic subtypes (epithelial, mixed, sarcomatoid) can be challenging.
      Pleural biopsy has been proposed as the diagnostic gold standard. We investigated
      the accuracy of open pleural biopsy for diagnosis and subtype identification in
      MPM. METHODS: Patients with suspected MPM routinely undergo open pleural biopsy
      to establish diagnosis. Those diagnosed definitively by pleural biopsy or
      cytology are offered pleurectomy or EPP dependent on stage and cardiorespiratory
      status. We reviewed medical records for all patients undergoing EPP at our
      institution, comparing tissue and subtype diagnosis at initial diagnostic biopsy
      versus definitive resection. RESULTS: Between 1988 and 2000, 305 of 332
      consecutive patients undergoing EPP had MPM. One patient diagnosed with MPM at
      pleural biopsy was misclassified. Subtype analysis at pleural biopsy proved
      correct in 80% (226/282). Most patients (174/192) with epithelial subtype at
      final diagnosis were diagnosed correctly at pleural biopsy. However, 44% (45/103)
      with pathologic diagnosis of nonepithelial subtype at resection were initially
      misdiagnosed with the epithelial subtype. The sensitivity of pleural biopsy for
      epithelial MPM was 97% with a specificity of 56%. CONCLUSIONS: Open pleural
      biopsy is accurate and should be considered the gold standard diagnostic method
      for MPM. It is less sensitive for determining histologic subclass, particularly
      with nonepithelial subtypes.

PMID- 15511474
TI  - Endoscopic mucosal resection as a staging technique to determine the depth of
      invasion of esophageal adenocarcinoma.
AB  - BACKGROUND: Endoscopic ablation and vagal-sparing esophagectomy offer the
      potential for reduced morbidity in patients with high-grade dysplasia or early
      esophageal adenocarcinoma, but neither includes a lymphadenectomy. Although
      adequate for intramucosal tumors, both are potentially inadequate for patients
      with submucosal tumor invasion given the high prevalence of nodal metastases with
      these lesions. Currently there is no test including endoscopic ultrasound that
      can accurately determine whether a small tumor is confined to the mucosa or has
      penetrated into the submucosa. The aim of this study was to compare the
      pathologic depth of invasion by endoscopic mucosal resection with findings and
      outcome after surgical resection to assess the accuracy and reliability of
      endoscopic mucosal resection for staging early esophageal adenocarcinoma.
      METHODS: From 2001 to 2003, 7 patients presented with small, endoscopically
      visible adenocarcinomas. All underwent endoscopic mucosal resection followed by
      surgical resection. RESULTS: Analysis of the resected specimens confirmed that
      the endoscopic mucosal resection had accurately determined the depth of tumor
      invasion in all patients, and had completely excised the lesion in all but 1
      patient (86%). Lymph node dissection was included as part of the resection in 2
      patients with submucosal invasion by endoscopic mucosal resection, and a vagal
      sparing esophagectomy was used in the 5 patients with only intramucosal tumors.
      All patients are alive and disease-free at a median follow-up of 7 months.
      CONCLUSIONS: Endoscopic mucosal resection accurately determines the depth of
      tumor invasion, and should be used as a staging procedure in patients with early
      esophageal cancer when therapies that do not include a lymphadenectomy are
      considered.

PMID- 15511475
TI  - Induction therapy does not increase surgical morbidity after esophagectomy for
      cancer.
AB  - BACKGROUND: A complete pathological response after induction therapy for
      esophageal cancer offers survival benefits, but induction therapy may increase
      the risk of postoperative complications and mortality. METHODS: We performed a
      retrospective review of consecutive patients who underwent esophagectomy for
      esophageal cancer to identify preoperative predictors of complications and assess
      the possible influence of induction therapy on surgical outcomes. RESULTS:
      Between 1988 and 2003, 170 esophagectomies were performed on our service; 95
      (55.9%) underwent surgery alone and 75 (44.1%) received preoperative
      chemotherapy, 35 of whom also had preoperative radiation therapy. Based on
      multivariable regression analyses, independent covariates for complication
      categories included performance status (pulmonary, cardiovascular, total
      complications, and death), age (cardiovascular and other complications), and
      FEV(1)% (pulmonary complications). Whether patients received induction therapy
      was unrelated to the incidence of postoperative complications. CONCLUSIONS: We
      found no evidence that induction therapy adversely influences the incidence of
      postoperative morbidity or mortality after esophagectomy for cancer.

PMID- 15511476
TI  - ERBB2 amplifications in esophageal adenocarcinoma.
AB  - BACKGROUND: ERBB2 (v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, Her
      2-neu) gene amplification and overexpression has been reported in several types
      of cancer. The purpose of this study was to (1) determine the frequency of ERBB2
      amplification (in comparison to other proto-oncogenes) in tumors from patients
      with esophageal adenocarcinoma, (2) characterize structural details of an ERBB2
      amplicon in the esophageal adenocarcinoma cell line OE19 (contains a 100-fold
      ERBB2 amplification), and (3) test whether growth of the OE19 cell line is
      sensitive to the ERBB2 inhibitor trastuzumab (Herceptin; Genetech, Inc, San
      Francisco, CA). METHODS: First, we determined the frequency, by Southern blotting
      techniques, of amplification of ERBB2 and 13 other proto-oncogenes in a panel of
      25 esophageal adenocarcinoma tumors. Then, in a second panel of 10 tumor
      specimens, expression levels of the ERBB2 gene and of several other genes that
      flank ERBB2 on chromosome 17 were determined by microarray analysis. Next we
      characterized the ERBB2 amplicon in the esophageal adenocarcinoma cell line OE19
      using cytogenetic methods and a Rec-A protein assisted restriction endonuclease
      mapping technique. Finally, an in vitro growth inhibition assay was used to
      measure the sensitivity of OE19 and OE33 cells to treatment with trastuzumab
      (humanized antibody to ERBB2). RESULTS: ERBB2 was the most frequently amplified
      proto-oncogene among 25 esophageal adenocarcinoma tumors tested (greater than 10
      fold amplification in 3 of 25 (12%) tumors tested). The OE19 cell line contains a
      100-fold amplification of the ERBB2 gene, and highly expresses its messenger
      ribonucleic acid. Transcripts from genes that flank ERBB2 including GRB7, a
      protein linked to metastasis in esophageal cancer, also showed high levels of
      expression. In OE19 cells, the ERBB2 amplicon was localized to a homogeneously
      staining region of chromosome 14. Southern blots from the Rec-A protein assisted
      restriction endonuclease cleavage mapping experiments in OE19 showed a strong
      band of 210 kilobases in size, demonstrating that the main amplicon was a tandem
      repeat. In the in vitro growth inhibition assay, trastuzumab inhibited the OE19
      and OE33 cells growth by 49% and 20%, respectively, at a saturating concentration
      of 20 microg/mL. CONCLUSIONS: ERBB2 is the most frequently amplified proto
      oncogene in esophageal adenocarcinoma among the genes that we tested. In the OE19
      esophageal adenocarcinoma cell line, the ERBB2 amplicon is translocated onto
      chromosome 14, is amplified 100-fold at the deoxyribonucleic acid level, and is
      highly overexpressed at the messenger ribonucleic acid level. Finally, the growth
      of this cell line was inhibited by incubation with trastuzumab. These results
      demonstrate that a substantial number of esophageal adenocarcinomas have
      amplified copies of the ERBB2 gene, and that they may be responsive to ERBB2
      targeted therapies such as trastuzumab.

PMID- 15511477
TI  - Long-term results of thoracoscopic sympathectomy for hyperhidrosis.
AB  - BACKGROUND: Thoracoscopic sympathectomy is now the reference treatment for severe
      palmar hyperhidrosis, but this is offset by the occurrence of compensatory
      sweating. It has been studied in this series to improve the indications and
      information given to patients. METHODS: A retrospective review of 124 patients
      who were previously afflicted with bilateral thoracoscopic sympathectomy 6 years
      earlier was conducted. Patients were interviewed by postal questionnaire
      regarding the results and side effects. RESULTS: The series consisted of 89
      females (72%) and 35 males and the mean age was 28 years. The main indication was
      palmo-plantar hyperhidrosis (34%). The mean operating time was 36 minutes and
      there were no intraoperative complications. Postoperative pneumothorax occurred
      in 9 patients and 3 patients required a chest drain. The hospital stay was 36
      hours for 87.6% of the patients. Postoperative pain occurred in 78% of the
      patients. Neurologic complications (Horner syndrome, radial paralysis, and
      dysesthesia of the arm) occurred in 3 patients and disappeared after 2-6 months.
      Two patients required single-side reoperation because of failure with the first
      intervention. Eighty-nine replies to questionnaires were received (72%). The
      results for hands were favorable in 98% and in 63% for axillae. Compensatory
      sweating occurred in 87% of the patients (serious in 36% and incapacitating in
      6%). Despite this 90% of the patients were satisfied or very satisfied.
      CONCLUSIONS: This study confirms that thoracoscopic sympathectomy is a suitable
      method of treatment for severe palmar hyperhidrosis but emphasizes the need to
      offer the patient more informative information, especially regarding compensatory
      sweating which seems inescapable.

PMID- 15511478
TI  - Autologous peripheral blood stem cell transplantation for myocardial
      regeneration: a novel strategy for cell collection and surgical injection.
AB  - PURPOSE: Bone-marrow and peripheral blood-derived stem cells can be used as
      stimulators of myogenesis and angiogenesis. We describe an original technique for
      collection and surgical intramyocardial injection of peripheral blood-derived
      stem cells. DESCRIPTION: Stem cells are mobilized from the bone marrow by means
      of subcutaneous administration of Lenogastrim (Granocyte 34 [Aventis Pharma,
      Milan, Italy]) for 4 days. Then the day before the operation the peripheral blood
      derived stem cells are collected by means of apheresis and processed in order to
      obtain the CD 133+ cells. Cells are injected into the myocardium in a beating
      heart in order to induce angiogenesis locally or myogenesis, or both. When
      necessary, off-pump coronary artery bypass grafting is previously accomplished.
      EVALUATION: Thus far we have investigated 4 patients (3 patients who have
      received off-pump peripheral blood stem cell injection and coronary bypass
      grafting through median sternotomies, and 1 patient who underwent cell transplant
      alone through a minimally-invasive transdiaphragmatic approach). No complications
      were noted at a mean of 4 months after surgery. CONCLUSIONS: This novel method of
      peripheral bone marrow stem cell collection and intramyocardial injection seems
      to be safe, feasible, and reproducible. However, there is need of further
      evidence to definitely assess safety issues and clinical results.

PMID- 15511479
TI  - Invited commentary.

PMID- 15511480
TI  - New intraluminal coronary shunt tube for off-pump coronary artery bypass
      grafting.
AB  - PURPOSE: In cooperation with JMS Co., Ltd. (Hiroshima, Japan), we have developed
      a new intraluminal coronary shunt tube to allow easier, safer, and more accurate
      off-pump coronary artery bypass grafting (OPCABG). DESCRIPTION: Between September
      2000 and July 2002, the new shunt tube was used in 100 consecutive patients
      undergoing OPCABG. Patient characteristics, experimental data, and clinical
      results for our new shunt tube are provided. EVALUATION: Our new coronary shunt
      tube was easily implanted in nearly all (97.2%) target vessels during
      reconstructions. All 100 cases were performed completely during off-pump
      operation. Early postoperative coronary angiography was performed in all 100
      cases, demonstrating excellent patency in arterial grafts (99.5%) and venous
      grafts (96.2%). The shunt tube displayed good flow rates under experimental
      conditions according to diameter, and effectively prevented ischemia during
      coronary arterial reconstructions in all cases. No target vessels were injured on
      insertion or removal of shunt tubes. Neither perioperative complications nor
      hospital deaths were encountered. CONCLUSIONS: This new shunt tube improves the
      safety, accuracy, and ease of OPCABG surgery.

PMID- 15511481
TI  - Invited commentary.

PMID- 15511482
TI  - Intercontinental LVAS patient transport.
AB  - Mechanical circulatory support is currently indicated for patients with cardiac
      insufficiency as a bridge to transplantation or as a bridge to recovery. These
      systems continue to evolve and improve, and many patients (after they are
      stabilized) are now able to be discharged from the hospital. This article reports
      our experience with the intercontinental transportation of a patient while being
      supported with a Novacor left ventricular assist system (WorldHeart Corp, Ottawa,
      Canada). While in Japan, the Canadian patient suffered a myocardial infarction
      and despite coronary artery bypass grafting, the patient remained in a low
      cardiac output state. After implantation of the left ventricular assist system in
      Japan, the patient was stabilized and transported by a commercial airline to
      Canada where he underwent successful heart transplantation.

PMID- 15511483
TI  - Heart transplantation in a patient with a left ventricular assist device and
      methicillin-resistant Staphylococcus aureus infection.
AB  - We report a patient who underwent implantation of a DeBakey left-ventricular
      assist device and developed a methicillin-resistant Staphylococcus aureus drive
      line infection on postoperative day 304. The patient was forwarded to urgent
      heart transplantation with a successful outcome.

PMID- 15511484
TI  - Regurgitation of the native aortic valve caused by thrombus formation after
      heterotopic heart transplantation.
AB  - A 61-year-old man, who had undergone heterotopic heart transplantation, had
      severe regurgitation through his native aortic valve develop 16 years later,
      which caused severe heart failure. At operation the regurgitation was found to be
      due to development of an organized thrombus in the sinuses of Valsalva tethering
      aortic leaflets. The management of this previously undescribed complication of
      heterotopic heart transplantation and the implications for other groups of
      patients (such as those receiving treatment with a left ventricular assist
      device) are discussed.

PMID- 15511485
TI  - Giant left ventricular pseudoaneurysm after mitral valve replacement and
      myocardial infarction.
AB  - Left ventricular pseudoaneurysm is a rare but serious complication of mitral
      valve replacement or myocardial infarction. Prompt surgical correction is
      mandatory in cases of a large left ventricular pseudoaneurysm. A 70-year-old man
      had a giant left ventricular pseudoaneurysm after myocardial infarction and
      mitral valve replacement. The orifice of the pseudoaneurysm was closed with an e
      polytetrafluoroethylene patch and the pseudoaneurysmal wall was almost resected.

PMID- 15511486
TI  - Mitral valve replacement in a patient with a collapsed lung and a giant abscess.
AB  - Mitral valve replacement was performed on a 75-year-old man with a history of
      pulmonary tuberculosis. Computed tomography showed a collapsed left lung and
      counterclockwise rotation of the heart due to a hard abscess. Surgery was
      performed through a median sternotomy, and extensive pericardial suspension was
      useful for obtaining an adequate view. Despite poor pulmonary function, the
      patient was extubated on the day of surgery and had an uneventful postoperative
      course. Cardiac surgery can be performed in patients with a single functional
      lung if their preoperative respiratory function is good enough to have daily life
      without dyspnea.

PMID- 15511487
TI  - Aortopulmonary fistula due to perforation of the aortic wall of a freestyle
      stentless valve.
AB  - Aortopulmonary fistula occurring as a result of a rupture of the aortic wall of a
      stentless valve has not been previously reported. A 71-year-old woman suffered
      aortopulmonary fistula 15 months after replacement of the aortic root with a
      Freestyle stentless valve (Medtronic, Inc, Minneapolis, MN) and Dacron graft
      extension to replace the aortic valve and the ascending aorta to the aortic arch.
      We describe the successful repair of the fistula and simultaneous mitral valve
      replacement. The cause of deterioration of the aortic wall of the stentless
      valve, which gradually developed and ruptured, may have been primarily structural
      injury at the previous operation, with additional insult from the surgical
      adhesive used.

PMID- 15511488
TI  - Surgery for anomalous origin of the right coronary artery from the left aortic
      sinus.
AB  - This case report illustrates the presentation, diagnosis, and surgical management
      of an anomalous origin of the right coronary artery from the left coronary sinus
      in a young adult in whom the right coronary artery was reimplanted directly onto
      the aorta, rather than bypassed, as is typically done.

PMID- 15511489
TI  - Severe stenosis of anastomoses by using the symmetry aortic connector system.
AB  - The St. Jude Medical Symmetry Aortic Connector System was developed to create the
      proximal vein graft anastomoses in coronary artery bypass grafting. We describe
      three symptomatic patients with severe stenosis of the proximal anastomosis
      several months after using the Symmetry aortic connector system. Intravascular
      ultrasound study showed anastomotic neointimal hyperplasia.

PMID- 15511490
TI  - Giant pseudoaneurysm from Vieussens' arterial ring.
AB  - A giant coronary pseudoaneurysm of uncertain cause, arising from Vieussens'
      arterial ring, was preoperatively diagnosed in an oligosymptomatic female
      patient. Successful off-pump surgical excision without additional bypass grafting
      was performed. Difficulties in diagnostic algorithm, as well as possible cause
      and extremely rare localization were discussed.

PMID- 15511491
TI  - Prandial atrial fibrillation: off-pump pulmonary vein isolation with hiatal
      hernia repair.
AB  - Frequent palpitations with eating developed in a 62-year-old man with a history
      of typical gastroesophageal reflux successfully treated by Nissen fundoplication
      5 years previously. A Holter monitor demonstrated paroxysmal atrial fibrillation
      associated with eating. Barium swallow showed a slipped Nissen fundoplication
      with herniation into the chest. Under a single anesthetic, the patient had median
      sternotomy and off-pump pulmonary vein isolation with a bipolar radiofrequency
      clamp and transabdominal redo-Nissen fundoplication. A 24-hour Holter monitor
      performed 6 weeks after operation demonstrated a normal sinus rhythm with no
      atrial fibrillation. Barium swallow demonstrated an intact infradiaphragmatic
      repair.

PMID- 15511492
TI  - Use of saphenous vein graft in axillary artery cannulation.
AB  - Axillary artery cannulation for cardiopulmonary bypass is becoming increasingly
      used for surgery of aortic dissections for reoperations and extensively diseased
      ascending aortas. This can be achieved either directly or with a graft. We
      describe a case with a repair of chronic type A dissection in which axillary
      cannulation was achieved by placing the arterial cannula into a saphenous vein
      graft that had been anastomosed end-to-side to the axillary artery. This provides
      a natural, inexpensive, readily available, and more hemostatic alternative to the
      use of prosthetic grafts.

PMID- 15511493
TI  - A case of pulmonary artery sling associated with long-segment funnel trachea and
      bronchus suis.
AB  - An infant with pulmonary sling syndrome associated with an abnormal branching of
      the trachea, bronchus suis, complicated by long segment intrathoracic tracheal
      stenosis (ie, "funnel trachea") and concomitant tracheomalacia underwent
      reoperation at 5 months of age. We review the anatomy of this rare entity and
      describe the surgical technique to avoid the residual stenosis.

PMID- 15511494
TI  - Alveolar adenoma.
AB  - Alveolar adenoma of the lung is a rare benign neoplasm with proliferation of
      alveolar epithelium and septal mesenchyme. This unusual neoplasm presents as a
      solitary mass on chest roentgenograms, especially in older, asymptomatic
      patients. We report a case of this unusual neoplasm and describe the histologic
      and radiographic features of this tumor, which should be included in the
      differential diagnosis of a solitary pulmonary mass.

PMID- 15511495
TI  - Video-assisted thoracoscopic wedge resection for pulmonary sequestration.
AB  - A 60-year-old woman underwent a video-assisted thoracoscopic wedge resection of
      intralobar pulmonary sequestration instead of a lobotomy because the lesion was
      localized in the right basal segment. Preoperative 3-dimensional computed
      tomography was useful for identifying an aberrant artery arising from the
      thoracic aorta and distributing to the lesion. A successful outcome more than 4
      years after the surgery indicates that a wedge resection under video-assisted
      thoracoscopy may prove to be a therapeutic option for localized pulmonary
      sequestration.

PMID- 15511496
TI  - Cavernoscopic removal of a fungus ball for pulmonary complex aspergilloma.
AB  - Lobectomy of the lung for aspergilloma is not always appropriate in elderly
      patients because of the high surgical risk. A 78-year-old male diagnosed with
      complex aspergilloma was referred to our hospital for recurrent hemoptysis.
      Because he refused lobectomy, we conducted a cavernoscopic removal of the fungus
      ball. The site of the skin incision was carefully designed preoperatively. After
      achieving access, the fungus ball was removed piece by piece under endoscopic
      view. Intraoperative blood loss equaled 30 mL. At 5 months postoperative follow
      up, the patient had no evidence of recurrence. This procedure may be useful in
      some patients with complex aspergilloma.

PMID- 15511497
TI  - Congenital membranous obstruction of the inferior vena cava.

PMID- 15511498
TI  - Intrathoracic giant lipoma.

PMID- 15511500
TI  - Konno procedure using atrioventricular groove patch plasty after arterial switch
      operation.
AB  - A patient with transposition of the great arteries accompanied by Shaher type 9
      coronary anatomy experienced the development of progressive neoaortic valvular
      regurgitation with a small annulus, supravalvular stenosis, and neopulmonary
      valvular and supravalvular stenoses 15 years after an arterial switch operation.
      To implant a prosthetic valve clinically adequate in size, the Konno procedure
      was necessary. However, the right coronary anatomy precluded the original Konno
      procedure. My colleagues and I accomplished neoaortic anterior annular
      enlargement in this case by using atrioventricular groove patch plasty without
      jeopardizing the right coronary artery, and this resulted in a satisfactory
      outcome.

PMID- 15511499
TI  - Partial translocation for repair of left ventricular rupture after mitral valve
      replacement.
AB  - A new partial translocation technique to repair left ventricular rupture after
      mitral valve replacement and reimplant a mitral prosthesis is described. We
      repaired a tear from the interior by using mattress stitches buttressed with
      strips of Dacron felt, constructed a new annulus with a crescent-shaped piece of
      bovine pericardium on the left atrial wall above the repaired mitral annulus, and
      implanted a new prosthesis by using the newly constructed mitral annulus. We
      consider avoidance of mechanical stress by the prosthesis on the repaired site
      crucial to a successful outcome, and this new method is useful.

PMID- 15511501
TI  - Systematic traction techniques in minimal-access pediatric cardiac surgery.
AB  - Minimal-access pediatric cardiac surgery is now common in the treatment of simple
      congenital heart defects. However, methods of securing a good, unobstructed view
      for surgery and the difficulties of working in a deep, narrow field jeopardize
      safety in surgical procedures, especially for less experienced surgeons have been
      described. Our systematic, step-by-step traction techniques on the skin, the
      pericardium, the right atrial appendage, the aortic root, both venae cavae, and
      the free wall of the right ventricular outflow, using a mechanical retractor and
      traction sutures, facilitate surgical field exposure and the achievement of
      safety. As described below, our procedures are simple, allow direct inspection,
      and assist those working toward technical mastery.

PMID- 15511502
TI  - Video-assisted thoracic surgery upper lobe trisegmentectomy for early-stage left
      apical lung cancer.
AB  - Resection of the left upper lobe with preservation of the lingula is the anatomic
      equivalent of a right upper lobectomy with preservation of the right middle lobe.
      Therefore, our standard operation for a small apical tumor in the left upper lobe
      has been an apical trisegmentectomy. The purpose of this article is to review our
      experience with the procedure by video-assisted thoracic surgery (VATS) and to
      describe the operative technique for a VATS apical trisegmentectomy. Eleven
      patients underwent the procedure with no deaths, low morbidity, and good initial
      disease-free survival. A VATS apical trisegmentectomy seems to be a feasible and
      reasonable treatment for small stage I lung cancers at the apex of the left upper
      lobe.

PMID- 15511503
TI  - Hybrid coronary revascularization in the era of drug-eluting stents.
AB  - Left internal mammary artery to left anterior descending coronary artery bypass
      grafting integrated with percutaneous coronary angioplasty (hybrid procedure)
      offers multivessel revascularization with minimal morbidity in high-risk
      patients. This is caused in part by the avoidance of cardiopulmonary bypass
      related morbidity and manipulation of the aorta coupled with minimally invasive
      techniques. Hybrid revascularization is currently reserved for particularly high
      risk patients or those with favorable anatomic variants however, largely because
      of the emergence of off-pump coronary artery bypass grafting, which permits more
      complete multivessel revascularization, with low morbidity in high-risk groups.
      The wider introduction of hybrid revascularization is limited chiefly by the high
      number of repeat interventions compared with off-pump coronary artery bypass
      grafting, which occurs because of the target vessel failure rate of percutaneous
      coronary intervention. Other demerits are the costs and logistic problems
      associated with performing two procedures with differing periprocedural
      management protocols. Recently, drug-eluting stents have reduced the need for
      repeat intervention after percutaneous coronary intervention, and this has raised
      the possibility that the results of hybrid revascularization may now equal or
      even better those of off-pump coronary artery bypass grafting. Although
      undoubtedly effective at reducing in-stent restenosis, drug-eluting stents will
      not address the issues of incomplete revascularization or the logistic problems
      associated with hybrid. Uncertainty regarding the long-term effectiveness of drug
      eluting stents in many patients, as well as their high cost when compared with
      those of off-pump coronary artery bypass grafting surgery, also militates against
      the wider introduction of hybrid revascularization.

PMID- 15511504
TI  - Cardiac surgery risk models: a position article.
AB  - Differences in medical outcomes may result from disease severity, treatment
      effectiveness, or chance. Because most outcome studies are observational rather
      than randomized, risk adjustment is necessary to account for case mix. This has
      usually been accomplished through the use of standard logistic regression models,
      although Bayesian models, hierarchical linear models, and machine-learning
      techniques such as neural networks have also been used. Many factors are
      essential to insuring the accuracy and usefulness of such models, including
      selection of an appropriate clinical database, inclusion of critical core
      variables, precise definitions for predictor variables and endpoints, proper
      model development, validation, and audit. Risk models may be used to assess the
      impact of specific predictors on outcome, to aid in patient counseling and
      treatment selection, to profile provider quality, and to serve as the basis of
      continuous quality improvement activities.

PMID- 15511506
TI  - Graft occlusion after deployment of the aortic connector symmetry system: is
      anticoagulation a necessity?

PMID- 15511507
TI  - Repair of Barlow's mitral valve: to do or not to do.

PMID- 15511509
TI  - Acute renal injury and lowest hematocrit during cardiopulmonary bypass: not only
      a matter of cellular hypoxemia.

PMID- 15511513
TI  - Protection of a surgeon from dangerous needlesticks.

PMID- 15511514
TI  - Double-flap technique for repair of anomalous origin of right pulmonary artery
      from ascending aorta.

PMID- 15511515
TI  - Concomitant carotid endarterectomy and off-pump coronary revascularization.

PMID- 15511516
TI  - Pitfalls in the measurement of serum VEGF in children with congenital heart
      disease.

PMID- 15511519
TI  - Successful repair of tetralogy of Fallot with aortic valvular stenosis.

PMID- 15511520
TI  - Should lobectomy ever be the first choice for patients with small pulmonary
      lesions?

PMID- 15511522
TI  - The diagnostic approach to mediastinal masses.

PMID- 15511523
TI  - RecA-like motor ATPases--lessons from structures.
AB  - A large class of ATPases contains a RecA-like structural domain and uses the
      energy of nucleotide binding and hydrolysis to perform mechanical work, for
      example, to move polypeptides or nucleic acids. These ATPases include helicases,
      ABC transporters, clamp loaders, and proteases. The functional units of the
      ATPases contain different numbers of RecA-like domains, but the nucleotide is
      always bound at the interface between two adjacent RecA-like folds and the two
      domains move relative to one another during the ATPase cycle. The structures
      determined for different RecA-like motor ATPases begin to reveal how they move
      macromolecules.

PMID- 15511524
TI  - Molecular interference of Cd(2+) with Photosystem II.
AB  - Many heavy metals inhibit electron transfer reactions in Photosystem II (PSII).
      Cd(2+) is known to exchange, with high affinity in a slow reaction, for the
      Ca(2+) cofactor in the Ca/Mn cluster that constitutes the oxygen-evolving center.
      This results in inhibition of photosynthetic oxygen evolution. There are also
      indications that Cd(2+) binds to other sites in PSII, potentially to proton
      channels in analogy to heavy metal binding in photosynthetic reaction centers
      from purple bacteria. In search for the effects of Cd(2+)-binding to those sites,
      we have studied how Cd(2+) affects electron transfer reactions in PSII after
      short incubation times and in sites, which interact with Cd(2+) with low
      affinity. Overall electron transfer and partial electron transfer were studied by
      a combination of EPR spectroscopy of individual redox components, flash-induced
      variable fluorescence and steady state oxygen evolution measurements. Several
      effects of Cd(2+) were observed: (i) the amplitude of the flash-induced variable
      fluorescence was lost indicating that electron transfer from Y(Z) to P(680)(+)
      was inhibited; (ii) Q(A)(-) to Q(B) electron transfer was slowed down; (iii) the
      S(2) state multiline EPR signal was not observable; (iv) steady state oxygen
      evolution was inhibited in both a high-affinity and a low-affinity site; (v) the
      spectral shape of the EPR signal from Q(A)(-)Fe(2+) was modified but its
      amplitude was not sensitive to the presence of Cd(2+). In addition, the presence
      of both Ca(2+) and DCMU abolished Cd(2+)-induced effects partially and in
      different sites. The number of sites for Cd(2+) binding and the possible nature
      of these sites are discussed.

PMID- 15511525
TI  - Respiratory terminal oxidases in the facultative chemoheterotrophic and
      dinitrogen fixing cyanobacterium Anabaena variabilis strain ATCC 29413:
      characterization of the cox2 locus.
AB  - Upon nitrogen step-down, some filamentous cyanobacteria differentiate
      heterocysts, cells specialized for dinitrogen fixation, a highly oxygen sensitive
      process. Aerobic respiration is one of the mechanisms responsible for a
      microaerobic environment in heterocysts and respiratory terminal oxidases are the
      key enzymes of the respiratory chains. We used Anabaena variabilis strain ATCC
      29413, because it is one of the few heterocyst-forming facultatively
      chemoheterotrophic cyanobacteria amenable to genetic manipulation. Using PCR with
      degenerate primers, we found four gene loci for respiratory terminal oxidases,
      three of which code for putative cytochrome c oxidases and one whose genes are
      homologous to cytochrome bd-type quinol oxidases. One cytochrome c oxidase, Cox2,
      was the only enzyme whose expression, tested by RT-PCR, was evidently up
      regulated in diazotrophy, and therefore cloned, sequenced, and characterized. Up
      regulation of Cox2 was corroborated by Northern and primer extension analyses.
      Strains were constructed lacking Cox1 (a previously characterized cytochrome c
      oxidase), Cox2, or both, which all grew diazotrophically. In vitro cytochrome c
      oxidase and respiratory activities were determined in all strains, allowing for
      the first time to estimate the relative contributions to total respiration of the
      different respiratory electron transport branches under different external
      conditions. Especially adding fructose to the growth medium led to a dramatic
      enhancement of in vitro cytochrome c oxidation and in vivo respiratory activity
      without significantly influencing gene expression.

PMID- 15511526
TI  - Effect of deuterium oxide on contraction characteristics and ATPase activity in
      glycerinated single rabbit skeletal muscle fibers.
AB  - We studied the effect of deuterium oxide (D(2)O) on contraction characteristics
      and ATPase activity of single glycerinated muscle fibers of rabbit psoas. D(2)O
      increased the maximum isometric force P(0) by about 20%, while the force versus
      stiffness relation did not change appreciably. The maximum shortening velocity
      under zero load V(max) did not change appreciably in D(2)O, so that the force
      velocity (P-V) curve was scaled depending on the value of P(0). The Mg-ATPase
      activity of the fibers during generation of steady isometric force P(0) was
      reduced by about 50% in D(2)O. Based on the Huxley contraction model, these
      results can be accounted for in terms of D(2)O-induced changes in the rate
      constants f(1) and g(1) for making and breaking actin-myosin linkages in the
      isometric condition, in such a way that f(1)/(f(1)+g(1)) increases by about 20%,
      while (f(1)+g(1)) remains unchanged. The D(2)O effect at the molecular level is
      discussed in connection with biochemical studies on actomyosin ATPase.

PMID- 15511527
TI  - In vitro and in vivo studies of F(0)F(1)ATP synthase regulation by inhibitor
      protein IF(1) in goat heart.
AB  - A method has been developed to allow the level of F(0)F(1)ATP synthase capacity
      and the quantity of IF(1) bound to this enzyme be measured in single biopsy
      samples of goat heart. ATP synthase capacity was determined from the maximal
      mitochondrial ATP hydrolysis rate and IF(1) content was determined by detergent
      extraction followed by blue native gel electrophoresis, two-dimensional SDS-PAGE
      and immunoblotting with anti-IF(1) antibodies. Anaesthetized open-chest goats
      were subjected to ischemic preconditioning and/or sudden increases of coronary
      blood flow (CBF) (reactive hyperemia). When hyperemia was induced before ischemic
      preconditioning, a steep increase in synthase capacity, followed by a deep
      decrease, was observed. In contrast, hyperemia did not affect synthase capacity
      when applied after ischemic preconditioning. Similar effects could be produced in
      vitro by treatment of heart biopsy samples with anoxia (down-regulation of the
      ATP synthase) or high-salt or high-pH buffers (up-regulation). We show that both
      in vitro and in vivo the same close inverse correlation exists between enzyme
      activity and IF(1) content, demonstrating that under all conditions tested the
      only significant modulator of the enzyme activity was IF(1). In addition, both in
      vivo and in vitro, 1.3-1.4 mol of IF(1) was predicted to fully inactivate 1 mol
      of synthase, thus excluding the existence of significant numbers of non
      inhibitory binding sites for IF(1) in the F(0) sector.

PMID- 15511528
TI  - Plastocyanin redox kinetics in spinach chloroplasts: evidence for disequilibrium
      in the high potential chain.
AB  - Reduction kinetics of cytochrome f, plastocyanin (PC) and P(700) ('high-potential
      chain') in thylakoids from spinach were followed after pre-oxidation by a
      saturating light pulse. We describe a novel approach to follow PC redox kinetics
      from deconvolution of 810-860 nm absorption changes. The equilibration between
      the redox-components was analyzed by plotting the redox state of cytochrome f and
      PC against that of P(700). In thylakoids with (1) diminished electron transport
      rate (adjusted with a cytochrome bf inhibitor) or (2) de-stacked grana,
      cytochrome f and PC relaxed close to their thermodynamic equilibriums with
      P(700). In stacked thylakoids with non-inhibited electron transport, the
      equilibration plots were complex and non-hyperbolic, suggesting that during fast
      electron flux, the 'high-potential chain' does not homogeneously equilibrate
      throughout the membrane. Apparent equilibrium constants <5 were calculated, which
      are below the thermodynamic equilibrium known for the 'high potential chain'. The
      disequilibrium found in stacked thylakoids with high electron fluxes is explained
      by restricted long-range PC diffusion. We develop a model assuming that about 30%
      of Photosystem I mainly located in grana end-membranes and margins rapidly
      equilibrate with cytochrome f via short-distance transluminal PC diffusion, while
      long-range lateral PC migration between grana cores and distant stroma lamellae
      is restricted. Implications for the electron flux control are discussed.

PMID- 15511529
TI  - Cross-linking of transmembrane helices in proton-translocating nicotinamide
      nucleotide transhydrogenase from Escherichia coli: implications for the structure
      and function of the membrane domain.
AB  - Proton-pumping nicotinamide nucleotide transhydrogenase from Escherichia coli
      contains an alpha and a beta subunit of 54 and 49 kDa, respectively, and is made
      up of three domains. Domain I (dI) and III (dIII) are hydrophilic and contain the
      NAD(H)- and NADP(H)-binding sites, respectively, whereas the hydrophobic domain
      II (dII) contains 13 transmembrane alpha-helices and harbours the proton channel.
      Using a cysteine-free transhydrogenase, the organization of dII and helix-helix
      distances were investigated by the introduction of one or two cysteines in helix
      helix loops on the periplasmic side. Mutants were subsequently cross-linked in
      the absence and presence of diamide and the bifunctional maleimide cross-linker o
      PDM (6 A), and visualized by SDS-PAGE. In the alpha(2)beta(2) tetramer, alphabeta
      cross-links were obtained with the alphaG476C-betaS2C, alphaG476C-betaT54C and
      alphaG476C-betaS183C double mutants. Significant alphaalpha cross-links were
      obtained with the alphaG476C single mutant in the loop connecting helix 3 and 4,
      whereas betabeta cross-links were obtained with the betaS2C, betaT54C and
      betaS183C single mutants in the beginning of helix 6, the loop between helix 7
      and 8 and the loop connecting helix 11 and 12, respectively. In a model based on
      13 mutants, the interface between the alpha and beta subunits in the dimer is
      lined along an axis formed by helices 3 and 4 from the alpha subunit and helices
      6, 7 and 8 from the beta subunit. In addition, helices 2 and 4 in the alpha
      subunit together with helices 6 and 12 in the beta subunit interact with their
      counterparts in the alpha(2)beta(2) tetramer. Each beta subunit in the
      alpha(2)beta(2) tetramer was concluded to contain a proton channel composed of
      the highly conserved helices 9, 10, 13 and 14.

PMID- 15511530
TI  - Kinetics and ion specificity of Na(+)/Ca(2+) exchange mediated by the
      reconstituted beef heart mitochondrial Na(+)/Ca(2+) antiporter.
AB  - The Na(+)/Ca(2+) antiporter was purified from beef heart mitochondria and
      reconstituted into liposomes containing fluorescent probes selective for Na(+) or
      Ca(2+). Na(+)/Ca(2+) exchange was strongly inhibited at alkaline pH, a property
      that is relevant to rapid Ca(2+) oscillations in mitochondria. The effect of pH
      was mediated entirely via an effect on the K(m) for Ca(2+). When present on the
      same side as Ca(2+), K(+) activated exchange by lowering the K(m) for Ca(2+) from
      2 to 0.9 microM. The K(m) for Na(+) was 8 mM. In the absence of Ca(2+), the
      exchanger catalyzed high rates of Na(+)/Li(+) and Na(+)/K(+) exchange. Diltiazem
      and tetraphenylphosphonium cation inhibited both Na(+)/Ca(2+) and Na(+)/K(+)
      exchange with IC(50) values of 10 and 0.6 microM, respectively. The V(max) for
      Na(+)/Ca(2+) exchange was increased about fourfold by bovine serum albumin, an
      effect that may reflect unmasking of an autoregulatory domain in the carrier
      protein.

PMID- 15511531
TI  - The stoichiometry of the chloroplast ATP synthase oligomer III in Chlamydomonas
      reinhardtii is not affected by the metabolic state.
AB  - The chloroplast H(+)-ATP synthase is a key component for the energy supply of
      higher plants and green algae. An oligomer of identical protein subunits III is
      responsible for the conversion of an electrochemical proton gradient into
      rotational motion. It is highly controversial if the oligomer III stoichiometry
      is affected by the metabolic state of any organism. Here, the intact oligomer III
      of the ATP synthase from Chlamydomonas reinhardtii has been isolated for the
      first time. Due to the importance of the subunit III stoichiometry for energy
      conversion, a gradient gel system was established to distinguish oligomers with
      different stoichiometries. With this methodology, a possible alterability of the
      stoichiometry in respect to the metabolic state of the cells was examined.
      Several growth parameters, i.e., light intensity, pH value, carbon source, and
      CO(2) concentration, were varied to determine their effects on the stoichiometry.
      Contrary to previous suggestions for E. coli, the oligomer III of the chloroplast
      H(+)-ATP synthase always consists of a constant number of monomers over a wide
      range of metabolic states. Furthermore, mass spectrometry indicates that subunit
      III from C. reinhardtii is not modified posttranslationally. Data suggest a
      subunit III stoichiometry of the algae ATP synthase divergent from higher plants.

PMID- 15511532
TI  - Dissipation of excess energy triggered by blue light in cyanobacteria with CP43'
      (isiA).
AB  - The chlorophyll-protein CP43' (isiA gene) induced by stress conditions in
      cyanobacteria is shown to serve as an antenna for Photosystem II (PSII), in
      addition to its known role as an antenna for Photosystem I (PSI). At high light
      intensity, this antenna is converted to an efficient trap for chlorophyll
      excitations that protects system II from photo-inhibition. In contrast to the
      'energy-dependent non-photochemical quenching' (NPQ) in chloroplasts, this
      photoprotective energy dissipation in cyanobacteria is triggered by blue light.
      The induction is proportional to light intensity. Induction and decay of the
      quenching exhibit the same large temperature-dependence.

PMID- 15511533
TI  - Coexistence of enzootic nasal adenocarcinoma and jaagsiekte retrovirus infection
      in sheep.
AB  - Ten sheep naturally affected with enzootic nasal adenocarcinoma (ENA), a disease
      associated with ovine enzootic nasal tumour virus (ENTV-1), were found also to be
      infected with jaagsiekte sheep retrovirus (JSRV), the causal agent of ovine
      pulmonary adenocarcinoma (OPA). Only one of the sheep showed OPA lung lesions.
      The animals belonged to 10 flocks located in a geographical area in which OPA is
      frequently seen. ENTV-1 was found in all the ENA tumours but only occasionally in
      extra-tumoral sites, confirming the results of a previous study. In contrast,
      JSRV had a disseminated tissue distribution, similar to that previously reported
      for animals infected with JSRV. However, the occurrence of JSRV in lymphoid
      tissues was clearly greater than in sheep infected with JSRV but with no lesions
      of ENA. The data suggested a synergistic relationship between ENTV-1 and JSRV,
      resulting in increased proliferation of JSRV.

PMID- 15511534
TI  - Versican and hyaluronan expression in canine colonic adenomas and carcinomas:
      relation to malignancy and depth of tumour invasion.
AB  - Changes in the production and structure of glycosaminoglycans and proteoglycans
      have been reported in many neoplastic tissues, and versican and hyaluronan
      (extracellular matrix components) are frequently increased in tumours and promote
      tumour progression. The distribution of chondroitin sulphate, versican and
      hyaluronan in normal canine colonic wall (n=10), and normal colonic lymph nodes
      (n=10), colonic adenomas (n=22), colonic adenocarcinomas (n=28), colonic
      undifferentiated carcinomas (n=7), and colonic lymph node metastases (n=8), was
      examined, with antibodies against chondroitin sulphate and versican, and a
      specific biotinylated probe for hyaluronan. The epithelial cells of the normal
      colonic mucosa were negative for all three substances, whereas the stromal tissue
      and lamina propria were moderately positive for chondroitin sulphate and
      hyaluronan, and weakly positive for versican. Chondroitin sulphate expression was
      increased in adenomas and carcinomas. However, there was no significant
      correlation between grade of tumour and degree of chondroitin sulphate
      expression. Versican expression was increased in the peritumoral stroma of
      adenocarcinomas and reduced in adenomas. A significant correlation was observed
      between grade of tumour and degree of versican expression. In 13 adenocarcinomas
      and undifferentiated carcinomas with invasion into all layers of the colorectum,
      the intensity of stromal versican expression was significantly related to the
      depth of invasion; the intensity was increased in the stroma of tumour islands in
      deep layers of the colonic wall. Unlike versican expression, hyaluronan
      expression was increased in the stromal tissue of both adenomas and carcinomas.
      However, the degree of stromal hyaluronan expression was unrelated to tumour
      grade and depth of tumour invasion. Hyaluronan was also expressed in the membrane
      and in the cytoplasm of tumour cells in 3/22 (14%) adenomas, 18/28 (64%)
      adenocarcinomas and 2/7 (29%) undifferentiated carcinomas. These results suggest
      that altered levels of both versican and hyaluronan in canine colonic tumours
      affect tumour progression.

PMID- 15511535
TI  - Distribution of vascular amyloid in scrapie-affected sheep with different
      genotypes.
AB  - Vascular amyloidosis in the brain is a pathological feature of ovine scrapie. Its
      occurrence varies between sheep, but whether this variation reflects differences
      in the host or the infecting scrapie strain (or both) is not clear. To
      investigate whether amyloidosis, like vacuolation and PrPsc distribution, is
      associated with genotype, the brains from 131 sheep representing a range of
      genotypes commonly associated with scrapie were examined histologically and
      immunohistochemically. Vascular amyloidosis was absent in 66 sheep, 59 of which
      were of the ARQ/ARQ genotype and seven the ARQ/AHQ genotype. In contrast, it was
      found in four of 39 ARQ/VRQ sheep (10.2%) and in 10 of 26 VRQ/VRQ sheep (38.4%).
      The distribution of amyloid was highly variable, but the most severely affected
      areas were the lateral geniculate nuclei (five cases) and the ventral thalamic
      nuclei (four cases). No amyloidosis was found in the medulla or in the basal
      nuclei. From this preliminary study it was concluded that amyloidosis is
      relatively rare in sheep with scrapie. Moreover, its occurrence appeared to
      depend on the presence of at least one valine at codon 136.

PMID- 15511536
TI  - Encephalomalacic lesions in pigs dually infected with porcine reproductive and
      respiratory syndrome virus and pseudorabies virus.
AB  - Four pigs (group 1) were infected with an aerosol containing porcine reproductive
      and respiratory syndrome virus (PRRSV) followed 7 days later by pseudorabies
      virus (PRV). Three further pigs (group 2) received PRRSV alone, two (group 3)
      received PRV alone, and two (group 4) remained as uninfected controls. Despite
      the admittedly small numbers of animals, the experiment appeared to throw light
      on aspects of synergy. Thus, the group 1 pigs showed severe neurological signs
      characterized by ataxia and muscular tremors. Total cell numbers in the
      bronchoalveolar lavage fluid were increased in all PRRSV-infected pigs, and PRRSV
      antigen was detected in the alveolar macrophages. Total cell numbers in the
      cerebrospinal fluid of group 1 pigs were considerably greater than those
      demonstrated in group 3, but no PRV antigen was found. Pigs of groups 1 and 2
      showed pulmonary lesions, characterized by interstitial pneumonia and PRRSV
      antigen immunolabelling. Non-suppurative encephalitis was found in five of the
      six pigs of groups 1 and 3. In particular, one group 1 animal had severe
      necrotizing encephalitis with intranuclear inclusion bodies and associated
      immunolabelling of PRV antigen. The other three group 1 pigs had prominent
      malacic lesions, with macrophages. These neuropathological findings strongly
      suggested that PRRSV infection in pigs enhances the severity of brain lesions
      caused PRV.

PMID- 15511537
TI  - Immunohistochemical detection of the expression of pro-inflammatory cytokines by
      ovine pulmonary macrophages.
AB  - The aim of this study was to determine the expression of three proinflammatory
      cytokines by pulmonary macrophages of sheep in paraffin wax-embedded tissue.
      Samples of lung from seven healthy sheep were fixed by immersion in either 10%
      neutral buffered formalin, acetic formalin, paraformaldehyde-lysine-periodate or
      Bouin's solution and processed for structural and immunohistochemical studies.
      The expression of interleukin (IL)-1alpha, IL-6 and tumour necrosis factor (TNF)
      alpha by pulmonary intravascular macrophages (PIMs) and alveolar macrophages
      (AMs) was detected by the avidin-biotin-peroxidase (ABC) technique. Bouin's
      solution proved to be the most suitable fixative and Tween 20 the most effective
      pretreatment for increasing permeability. Constitutive expression of IL-1alpha,
      IL-6 and TNF-alpha by both macrophage populations was detected. The number of
      PIMs expressing IL-1alpha (the predominant cytokine in ovine lung) was higher
      than that of AMs, while the expression of IL-6 was greater in AMs. No differences
      between PIMS and AMs were found in respect of TNF-alpha expression. The
      evaluation of cytokine expression represents a valuable tool for studying the
      pathogenesis of disease in the ovine lung.

PMID- 15511538
TI  - Determinants of early foot-and-mouth disease virus dynamics in pigs.
AB  - This paper provides a quantitative description of the early infectious process in
      pigs experimentally infected with foot-and-mouth disease virus (FMDV), obtained
      by dose-dependent, time course studies of viral load in serum. Pigs were
      inoculated by the intravenous or intradermal/subcutaneous route with FMDV and
      housed together in groups or individually. The effects of dose, inoculation route
      and exposure intensity on the replication of FMDV in vivo and the development of
      disease were studied. It was shown that the higher the dose, the shorter was the
      time to the start of active viraemia and to the onset of clinical signs. Exposure
      intensity and housing conditions influenced the viral dynamics of FMDV.
      Increasing the exposure intensity, by increasing the number of infected pigs
      housed together, had the effect of synchronizing the infection and reducing the
      variance in the start of active viraemia. Increasing the number of pigs housed
      together also increased the interaction between the pigs and the activity of
      individual pigs, which had the effect of shortening the time to the onset of
      clinical signs such as vesicle formation. Intradermal inoculation was more
      effective than intravenous inoculation for transmitting FMDV to pigs, resulting
      in shorter times to the start of active viraemia and in higher clinical scores.

PMID- 15511539
TI  - Use of automated real-time reverse transcription-polymerase chain reaction (RT
      PCR) to monitor experimental swine vesicular disease virus infection in pigs.
AB  - Automated real-time RT-PCR was evaluated as a diagnostic tool for swine vesicular
      disease virus (SVDV) infection on a range of samples (vesicular epithelium,
      serum, nasal swabs, faeces) from four inoculated and three in-contact pigs over a
      period of 28 days. Traditional diagnostic procedures (virus isolation, and ELISAs
      for antigen and antibody) were used in parallel. Each inoculated pig developed a
      significant viraemia and clinical disease, and excreted virus, which was
      transmitted to the in-contact animals. The latter, however, developed only a
      short-lived, low-level viraemia and no clinical disease. The RT-PCR and virus
      isolation were generally comparable in detecting SVDV in the serum and nasal
      swabs from inoculated and in-contact pigs up to day 6 after infection; it was
      possible, however, to isolate virus for a longer period from the faeces of a few
      pigs. This suggested that further optimization of the template extraction method
      was required to counteract the effects of RT-PCR inhibitors in faeces. It was
      concluded that the automated real-time RT-PCR is a useful diagnostic method for
      SVD in clinically or subclinically affected pigs and contributed to the study of
      the pathogenesis of SVD in the pigs.

PMID- 15511540
TI  - Early innate and longer-term adaptive cutaneous immunoinflammatory responses
      during primary infestation with the sheep scab mite, Psoroptes ovis.
AB  - Clinical observation has indicated that Psoroptes ovis mites provoke cutaneous
      inflammation within hours of experimental infestation, but the nature of this
      reaction has not been described. After infestation of naive sheep with ovigerous
      P. ovis mites, significant influxes of eosinophils (P<0.004) and neutrophils
      (P<0.001) were detected within 24 h. A significant (P<0.001) increase in mast
      cell numbers was observed by 96 h post-infestation. In addition, marked
      degenerative and proliferative epidermal lesions were evident 24 and 96 h,
      respectively, after infestation. The influence of the later, adaptive response on
      the cellular infiltrate at the advancing margin of the lesion and the original
      site of infestation was also monitored. Mast cell numbers were greatest at 21
      days while recruitment of eosinophils and neutrophils was maximal 63 days after
      infestation. Lesional severity was particularly pronounced from 42 to 63 days
      after infestation, but significant resolution had occurred by 84 days.
      Pathological changes at the advancing margin of the lesion were more severe than
      at the initial site of infestation, and this was reflected by the numbers of
      mites present. These data suggest that P. ovis elicits an early innate cutaneous
      response that is subsequently augmented by the development of an adaptive immune
      response, the intensity of which corresponds to the local population density of
      mites.

PMID- 15511541
TI  - Predictive modelling of post-onset xenoma growth during microsporidial gill
      disease (Loma salmonae) of salmonids.
AB  - Loma salmonae, an obligate intracellular microsporidian parasite, is the causal
      agent of microsporidial gill disease of salmon (MGDS), characterized by the
      production, growth and eventual rupture of spore-filled xenomas. MGDS in farmed
      chinook salmon remains occult until xenoma rupture, at which time the infected
      fish respond with intense branchitis and high rates of mortality. The present
      study showed that in experimentally infected fish the rate of change of xenoma
      diameter could be modelled through regression analysis, particularly through the
      period of 4-9 weeks post-infection, yielding the predictive equation: xenoma
      diameter=-42.9 microns +15.3 microns x (number of weeks post-infection). This
      provides a tool for diagnosticians to predict the time to xenoma rupture and
      hence to the initiation of the clinical phase of MGDS.

PMID- 15511542
TI  - Primary intra-axial leiomyosarcoma with obstructive hydrocephalus in a young dog.
AB  - A female Chihuahua dog aged 2 months had a 3-week history of progressive
      neurological signs (abnormal behaviour, disorientation, left-sided circling, and
      incessant whimpering). Necropsy revealed a primary leiomyosarcoma in the midline
      of the posterior thalamus with secondary obstructive hydrocephalus of the lateral
      ventricles. Grossly, an infiltrative, grey-white tumour had partly invaded the
      third ventricle. Histologically, the tumour formed hypercellular, interlacing
      bundles of neoplastic spindle cells with blunt-ended nuclei. Neoplastic cells
      were strongly immunoreactive for vimentin and both muscle-specific and alpha
      smooth muscle actin; MIB-1 immunoreactivity indicated a proliferative index of up
      to 5%. Leiomyosarcoma should be included in the differential diagnosis for
      primary brain tumours and hydrocephalus in young dogs.

PMID- 15511543
TI  - Primary diffuse tracheobronchial amyloidosis in a dog.
AB  - Primary diffuse tracheobronchial amyloidosis was diagnosed at necropsy in an
      intact male Akita dog aged 11 years, a non-productive chronic cough having been
      the only related clinical sign. Histologically, eosinophilic hyalinized deposits
      were found as a band in the lamina propria underneath the epithelium of the
      trachea and bronchi. When stained with Congo red, apple-green birefringence was
      observed in the deposits viewed with polarized light. The amyloid did not lose
      sensitivity to Congo red staining after incubation with potassium permanganate,
      indicating that it was of the AL (amyloid light chain) type. Ultrastructural
      features of the amyloid included a typical fibrillar meshwork with individual
      fibrils measuring 9.5 to 10.5 nm in diameter. This is the first report of primary
      diffuse tracheobronchial amyloidosis in the dog.

PMID- 15511544
TI  - Sexing of murine and bovine embryos by developmental arrest induced by high-titer
      H-Y antisera.
AB  - Murine and bovine embryos at the late morula stage were cultured in medium
      containing high-titer rat H-Y antisera. After 12h of incubation, embryos blocked
      at the late morulae stage were classified as males and those at the blastocyst
      stage were classified as females. Sexing of murine embryos by PCR and
      cytogenetics revealed that 83% of the embryos classified as males and 82% of
      those classified as females had their sex correctly predicted (P < 0.05). Bovine
      embryos were transferred to recipient females. Pregnancy rates were 71.4% (10/14)
      for embryos classified as males and 68.8% (11/16) for embryos classified as
      females. The sex was correctly predicted for 80% (8/10) of the embryos classified
      as males and for 81.8% (9/11) of those classified as females (overall accuracy,
      80.9%, P < 0.05). Therefore, the induction of developmental arrest by high-titer
      male-specific antisera was an efficient strategy for non-invasive embryo sexing.
      The procedure was straightforward and has considerable commercial potential for
      sexing bovine embryos.

PMID- 15511545
TI  - Comparison of four synchronization protocols for fixed-time bovine embryo
      transfer in Bos indicus x Bos taurus recipients.
AB  - The objective was to evaluate the effects of 400 IU of eCG given on Days 5 or 8
      of an estrus synchronization protocol with progesterone-releasing intravaginal
      devices (PRID) and estradiol benzoate (EB), in recipients for fixed-time embryo
      transfer. A secondary objective was to determine the effects of injectable
      progesterone (given concurrent with EB treatment). Three-hundred-and-four
      crossbred Bos taurus x Bos indicus beef heifers were randomly assigned to one of
      four treatment groups (2 x 2 factorial design). At unknown stages of the estrous
      cycle (Day 0), all heifers received a progesterone-releasing intravaginal device
      (PRID), plus 2mg of EB i.m., with or without a concurrent treatment of 50mg of
      progesterone i.m. Heifers were further subdivided to receive 0.15 mg of d
      cloprostenol (PGF) i.m. and 400 IU of eCG i.m. on Days 5 or 8. In all heifers,
      intravaginal devices were removed on Day 8 and 1mg of EB was given i.m. on Day 9
      (Day 10 was arbitrarily considered the day of estrus). On Day 17, all heifers
      with >1 CL or a single CL with a diameter > or =18 mm (based on ultrasonographic
      examination), received an in vitro produced (IVP) embryo by non-surgical
      transfer. On Day 17, there was an effect of day of eCG administration on the
      number of CL (1.35 +/- 0.08 versus 1.13 +/- 0.04, for Day 5 versus Day 8,
      respectively; P = 0.02) and (in a subset of 154 heifers) mean (+/-S.E.M.) plasma
      progesterone concentrations (2.41 +/- 0.26 versus 1.74 +/- 0.19 ng/mL; P = 0.03).
      Although the proportion of recipients transferred/treated and
      pregnant/transferred did not differ among groups, the proportion of recipients
      pregnant/treated tended (P = 0.1) to be higher in heifers treated with eCG on Day
      5 versus Day 8 (47.0% versus 40.7%, respectively). Progesterone treatment had no
      significant effect. In conclusion, treatment with eCG (and D-cloprostenol) on Day
      5 significantly increased the number of CL and plasma progesterone concentrations
      and tended to increase pregnancy rates, although progesterone treatment had no
      significant effect.

PMID- 15511546
TI  - Effects of oxygen tension on the development and quality of porcine in vitro
      fertilized embryos.
AB  - The present study was conducted to examine the effect of oxygen tension during in
      vitro culture (IVC) of porcine oocytes/embryos on their development and quality
      using two different culture systems. Porcine cumulus oocyte complexes (COCs) were
      matured (IVM) and fertilized (IVF) in vitro, and subsequently cultured for 6 days
      in a simple and economical portable incubator or a standard CO(2) incubator.
      While the same temperature (38.5 degrees C) and CO(2) concentration (5%) were
      used in the both systems, the portable incubator was operated in a negative air
      pressure (- 300 mmHg) to create an O(2) level at 8-10% (low O(2) concentration),
      or in a positive air pressure (high O(2) concentration). To compare the two
      culture systems, IVM and IVF of COCs and subsequent IVC of in vitro produced
      (IVP) embryos were carried out in the portable incubator with a low O(2)
      concentration (Group I) or in the standard incubator with a high O(2)
      concentration (Group II). To assess the effect of O(2) concentration on IVC of
      IVP embryos, some oocytes that had been cultured in the standard incubator for
      IVM and IVF were subsequently cultured in the portable incubator with a low O(2)
      concentration (Group III) or a high O(2) concentration (Group IV). The occurrence
      of DNA fragmentation in the blastocysts produced under different culture
      conditions was examined by TUNEL staining to assess embryo quality. The rates of
      oocytes that reached MII and were penetrated by spermatozoa following IVF did not
      differ between the two incubation systems. In contrast, the proportions of
      development to blastocysts and the mean cell number of blastocysts in Group I
      were higher than those in Group II and Group IV. The index of DNA-fragmented
      nucleus in the blastocysts of Group I was significantly lower than that in the
      blastocysts of Group II. Therefore, low oxygen tension during IVM, IVF and IVC
      enhanced the subsequent development of IVP embryos to the blastocyst stage and
      improved their quality.

PMID- 15511547
TI  - Origin of bovine follicular fluid and its effect during in vitro maturation on
      the developmental competence of bovine oocytes.
AB  - Protein supplementation during in vitro maturation can profoundly affect both the
      rate and overall efficiency of the maturation procedure. The present study was
      conducted to assess the ability of different concentrations (1, 5, and 10%) of
      bovine follicular fluid (bFF) to support in vitro maturation of oocytes and
      subsequent developmental capacity. The bFF was derived either from competent
      follicles ( > 8 mm) obtained by transvaginal recovery following superovulation or
      from a pool of small follicles (2-5 mm) from abbatoir-derived ovaries. Bovine
      oocytes were cultured for 24 h in synthetic oviduct fluid medium (m-SOF)
      supplemented with polyvinylpyrrolidone. Following fertilization and embryo
      culture, more oocytes (P < 0.05) reached the blastocyst stage when oocytes were
      cultured with 5% bFF from competent follicles (41 +/- 3.7%) compared with bFF
      derived from small follicles (16 +/- 2.9%). Estradiol and recombinant human
      follicle stimulating hormone added to the competent bFF during maturation acted
      in synergy to increase blastocyst production rate (P < 0.05); this blastocyst
      production rate (57 +/- 1.2%) was higher than those obtained with the addition of
      these two hormones to bFF derived from small follicles (26 +/- 2.9%). The quality
      of blastocysts obtained was reflected by inner cell mass (51.30 +/- 3.5 and 25.50
      +/- 3.7) and trophectoderm cell numbers (99.72 +/- 2.5 and 94.80 +/- 4.7) for bFF
      from competent and small follicles, respectively. In conclusion, follicular fluid
      originating from competent follicles increased the developmental competence of
      abbatoir-derived oocytes.

PMID- 15511548
TI  - A Bayesian approach to prediction of stallion daily sperm output.
AB  - In equine breeding, the number of spermatozoa ejaculated is considered an
      important factor in fertility. Methods for predicting the number of spermatozoa
      have been derived from semen collection procedures. A once-daily collection
      period for 10 days is a standard recommendation to predict long-term daily sperm
      output (DSO). The first objective of this study was to determine the precision or
      repeatability of these DSO predictions. Semen was collected and evaluated daily
      during four periods for 10 days, for 15 different stallions. The analytical
      methods utilized hierarchal Bayesian modeling as implemented by Gibbs Sampling.
      The overall population model showed an initial decline in total sperm number of
      1.54 billion spermatozoa per day until the observed mean change point of 4.71
      days, at which time mean DSO was estimated at 5.28 billion spermatozoa per day.
      The hierarchal model showed standard deviations in DSO within-stallion of 0.67
      billion spermatozoa per day and among-stallion of 1.86 billion spermatozoa per
      day. The study's second objective was to determine how testicular size affected
      DSO models. When the model was extended to include testicular size, the optimal
      prediction of DSO was that DSO = 0.79 + 0.018 x testicular size (in milliliters).
      Testicular size explained 36.5% of the among-stallion standard deviation in DSO,
      but was not significantly related to the mean number of collection-days required
      to reach DSO.

PMID- 15511549
TI  - Increasing feed intake in late gestation does not affect plasma progesterone
      concentration in the sow.
AB  - Rate of decline in plasma progesterone concentration may influence the success of
      lactogenesis in the sow. The aim of this experiment was to investigate whether
      progesterone concentration and rate of decline of progesterone in the
      periparturient sow could be manipulated by changing her feeding level. Forty-two
      sows received either 1.15 or 2 times maintenance energy daily from day 100 of
      gestation up until and including the day of farrowing. Blood samples were taken
      on days 98 (pre-treatment baseline) and 109 of gestation, during farrowing, 6h
      after farrowing and at 09:00 h for the 3 days following farrowing. Plasma
      progesterone concentration was determined and progesterone half-life was
      calculated for each sow. High intake feeding had no effect on plasma progesterone
      concentration at any time of sampling. Progesterone half-life averaged 41.2 +/-
      3.81 h and did not differ between treatments. There was no relationship between
      progesterone concentration, or half-life, and litter weight gain, although there
      was a weak correlation between decline in progesterone in the first 6h after
      birth and piglet growth rate from birth to 6 days of age (R(2) = 0.109, P <
      0.05). It was concluded that increasing feed intake in late gestation cannot be
      used to increase progesterone clearance rate and hasten the onset of lactogenesis
      in sows.

PMID- 15511550
TI  - Chemical activation of buffalo (Bubalus bubalis) oocytes by different methods:
      effects of aging on post-parthenogenetic development.
AB  - The possibility of artificially inducing activation of MII buffalo oocytes may
      allow us to evaluate indirectly the quality of oocytes after in vitro maturation.
      The aim of this work was to compare buffalo embryo development after IVF and
      after chemical activation by two different agents. A further goal was to evaluate
      the effects of aging of oocytes on post-parthenogenetic and post-fertilization
      development. In Experiment 1 cumulus-oocyte complexes (COCs) were recovered from
      abattoir-derived ovaries and matured in vitro. After IVM the COCs were either
      fertilized in vitro (positive control) or activated with ethanol and ionomycin,
      both followed by immediate exposure to 6-diethylaminopurine (6-DMAP) for 4 h. In
      vitro culture (IVC) was carried out up to the blastocyst stage. In Experiment 2
      COCs were matured in vitro for 18, 21, 24, 27 and 30 h before activation was
      triggered with ethanol, followed by 6-DMAP. In Experiment 3 COCs were fertilized
      in vitro at 18, 21, 24, 27 and 30 h post-maturation. Ethanol activation gave
      better results than the IVF control group, with higher cleavage rate (71.4 +/-
      7.8 versus 55.8 +/- 5.8, respectively; P < 0.05) and a higher proportion of
      oocytes developing into morulae-blastocysts (32.6 +/- 6.5 versus 22.9 +/- 7.5,
      respectively; P < 0.05). Within the activation groups, ethanol supported the
      highest development in terms of cleavage (71.4 +/- 7.8 versus 59.4 +/- 10.7; P <
      0.05) and morulae-blastocysts rate (32.6 +/- 6.5 versus 25.7 +/- 8.3; n.s.). It
      was also demonstrated that aging negatively affects post-parthenogenetic and post
      fertilization development.

PMID- 15511551
TI  - Effects of in vitro storage time and semen-extender on membrane quality of boar
      sperm assessed by flow cytometry.
AB  - The Norwegian AI company Norsvin has used the short-term semen-extender BTS to
      extend and store boar semen since the late 1980s. Fertility results have been
      consistent when extended semen has been used for AI within 3 days after
      collection, however, from a production and economic point of view it is
      preferable that semen stored for up to 5 days can be used. The aim of this study
      was to compare membrane quality of sperm stored in BTS for 3 days with sperm
      stored in the long-term semen-extenders Androstar, Mulberry III and X-cell for 5
      days. Using a split-sample design, plasma membrane- and acrosome-integrity were
      assessed flow cytometrically by use of Yo-Pro-1 and PNA-FITC, and fluidity and
      phospholipid asymmetry of the membrane were assessed by use of MC540 and Annexin
      V-FITC. Due to observed sperm fragmentation in Androstar after Day 1, the data
      for Androstar were excluded from the analyses. After 5 days of storage, the
      membrane quality of X-cell-stored sperm was not statistically different from that
      of sperm stored in BTS for 3 days, while membrane quality of sperm stored in
      Mulberry III was statistically better on Day 5 compared to BTS on Day 3. In
      conclusion, Mulberry III and X-cell preserve sperm quality, as well as that of
      BTS on Day 3, for up to 5 days after collection.

PMID- 15511552
TI  - Recovery, morphological quality, and in vitro maturation of follicular oocytes
      from bitches with pyometra.
AB  - The objective of this study was to collect oocytes from ovaries of bitches with
      pyometra and to characterize the quality of the oocytes recovered. In 10 of 12
      cases of pyometra, follicles with a diameter of 500 microm to 1mm were observed
      in the ovaries. A total of 710 oocytes were collected from 10 bitches by
      puncturing individual follicles after slicing the ovarian tissues. Oocyte
      recovery was successful from a bitch with severe clinical signs of pyometra. Of
      the oocytes collected, 53.5% were surrounded by > or =2 layers of cumulus cells,
      and 55.0% of these cumulus-oocyte complexes (COCs) had a darkly pigmented ooplasm
      >110 microm in diameter (large-dark COCs). The number of large-dark COCs per
      bitch varied from 1 to 72. A germinal vesicle with fine filaments of chromatin
      (Type A) was observed in 51.8% (range 21.1-100%) of the oocytes of large-dark
      COCs. Out of 50 oocytes cultured for 72 h, 6.0% developed to Metaphase II. In
      conclusion, there were many follicles with a diameter of 500 microm to 1mm in
      ovaries of bitches with pyometra, and many oocytes recovered from these follicles
      underwent meiotic maturation in vitro. The number of oocytes and COCs, and the
      morphological quality of the germinal vesicles varied among individual bitches.

PMID- 15511553
TI  - In vitro maturation of porcine oocytes using a defined medium and developmental
      capacity after intracytoplasmic sperm injection.
AB  - To establish a defined in vitro maturation culture system for porcine oocytes, we
      examined the effects of adding cysteine (Cys) and epidermal growth factor (EGF)
      to the maturation medium. Furthermore, to evaluate cytoplasmic maturation, we
      investigated GSH concentrations and embryo development after intracytoplasmic
      sperm injection (ICSI). The basic media for IVM were modified TCM199 containing
      10% newborn calf serum (NBCS) or 0.1% polyvinyl alcohol (PVA), supplemented with
      amino acids. Adding EGF (10 ng/ml) or EGF + Cys (0.57 mM) to the defined medium
      (0.1% PVA + amino acids) increased (P < 0.05) the rate of nuclear maturation
      relative to the defined medium (without these additives). After ICSI, oocytes
      matured in a medium supplemented with NBCS, Cys and EGF had a higher (P < 0.05)
      rate of pronuclear formation rate than oocytes matured in the defined IVM medium.
      Although there was no significant difference in cleavage rates between NBCS- and
      PVA-containing media supplemented with both Cys and EGF, the rate of blastocyst
      development was lower (P < 0.05) in the defined medium than in the NBCS
      containing medium. Intracellular GSH concentrations of oocytes matured in the
      NBCS- and PVA-containing media supplemented with both Cys and EGF were higher (P
      < 0.05) than in oocytes matured in PVA alone or in oocytes before maturation.
      Adding Cys and EGF to a defined medium for porcine IVM improved rates of nuclear
      maturation and cleaved oocytes following ICSI, probably due to increased GSH
      concentrations. Also, embryos derived from oocytes matured in the defined medium
      (with the addition of Cys and EGF) developed into blastocysts after ICSI.

PMID- 15511554
TI  - Fecal steroid analysis for monitoring reproduction in the sun bear (Helarctos
      malayanus).
AB  - Fecal steroid analyses were conducted on captive (n = 10) and free-ranging (n =
      2) sun bears (Helarctos malayanus) in order to establish a noninvasive technique
      for monitoring endocrine profiles during the estrous cycle and pregnancy.
      Secondly, the effect of the contraceptive porcine zona pellucida protein (PZP) on
      reproductive function was studied. Finally, we investigated whether the sun bear,
      naturally living in the aseasonal tropical forests of Southeast Asia, is a
      seasonal breeder. Fecal samples were collected over periods of 7-48 months in
      captive untreated (n = 8) and PZP-treated (n = 2) female sun bears. In addition
      samples were collected over a period of 12 months from radio-collared free
      ranging females (n = 2) in their natural habitat in Indonesian Borneo. Androgens,
      precursors of estrogens, were found to be reliable indicators of the follicular
      phase, whereas estrogens were found unsuitable. Pregnanediol assay was found to
      be a reliable indicator of luteal function. Results indicate that sun bears are
      polyestrous, nonseasonal breeders. Interestrus intervals in nonpregnant animals
      (n = 2), which were monitored for 27 months, were between 140 and 216 days.
      Luteal phases (89.6 +/- 3.7 days; n = 9) were preceded by androgen peaks of 15.2
      +/- 1.0 days (n = 10). Hormonal profiles of two females treated with PZP
      indicated missing ovarian activity in one, and persistent follicular and luteal
      activity in another animal. However, extended periods of missing ovarian, and
      persistent follicular and luteal activity were also observed in other sun bears
      studied.

PMID- 15511555
TI  - Oxidation states of uranium in depleted uranium particles from Kuwait.
AB  - The oxidation states of uranium in depleted uranium (DU) particles were
      determined by synchrotron radiation based mu-XANES, applied to individual
      particles isolated from selected samples collected at different sites in Kuwait.
      Based on scanning electron microscopy with X-ray microanalysis prior to mu-XANES,
      DU particles ranging from submicrons to several hundred micrometers were
      observed. The median particle size depended on sources and sampling sites; small
      sized particles (median 13 microm) were identified in swipes taken from the
      inside of DU penetrators holes in tanks and in sandy soil collected below DU
      penetrators, while larger particles (median 44 microm) were associated with fire
      in a DU ammunition storage facility. Furthermore, the (236)U/(235)U ratios
      obtained from accelerator mass spectrometry demonstrated that uranium in the DU
      particles originated from reprocessed fuel (about 10(-2) in DU from the
      ammunition facility, about 10(-3) for DU in swipes). Compared to well-defined
      standards, all investigated DU particles were oxidized. Uranium particles
      collected from swipes were characterized as UO(2), U(3)O(8) or a mixture of these
      oxidized forms, similar to that observed in DU affected areas in Kosovo. Uranium
      particles formed during fire in the DU ammunition facility were, however, present
      as oxidation state +5 and +6, with XANES spectra similar to solid uranyl
      standards. Environmental or health impact assessments for areas affected by DU
      munitions should therefore take into account the presence of respiratory UO(2),
      U(3)O(8) and even UO(3) particles, their corresponding weathering rates and the
      subsequent mobilisation of U from oxidized DU particles.

PMID- 15511556
TI  - Radon concentration in soil gas around local disjunctive tectonic zones in the
      Krakow area.
AB  - The purpose of this study was to investigate radon in the vicinity of geologic
      fault zones within the Krakow region of Poland, and to determine the influence of
      such formations on enhanced radon concentrations in soil. Radon ((222)Rn and
      (220)Rn) concentration measurements in soil gas (using ionization chamber
      AlphaGUARD PQ2000 PRO and diffusion chambers with CR-39 detectors), as well as
      radioactive natural isotopes of radium, thorium and potassium in soil samples
      (using gamma ray spectrometry with NaI(Tl) and HPGe detectors), were performed.
      Site selection was based on a geological map of Krakow. Geophysical methods
      (ground penetrating radar and shallow acoustic seismic) were applied to recognize
      the geological structure of the area and to locate the predicted courses of
      faults. Elevated levels of radon and thoron in soil gas were found in the study
      area when compared with those observed in an earlier survey covering Krakow
      agglomeration. For (222)Rn, the arithmetic mean of registered concentration
      values was 39 kBq/m(3) (median: 35.5 kBq/m(3)). For (220)Rn, the arithmetic mean
      was 10.8 kBq/m(3) and median 11.8 kBq/m(3).

PMID- 15511557
TI  - The removal of uranium from mining waste water using algal/microbial biomass.
AB  - We describe a three step process for the removal of uranium (U) from dilute waste
      waters. Step one involves the sequestration of U on, in, and around aquatic
      plants such as algae. Cell wall ligands efficiently remove U(VI) from waste
      water. Growing algae continuously renew the cellular surface area. Step 2 is the
      removal of U-algal particulates from the water column to the sediments. Step 3
      involves reducing U(VI) to U(IV) and transforming the ions into stable
      precipitates in the sediments. The algal cells provide organic carbon and other
      nutrients to heterotrophic microbial consortia to maintain the low E(H), within
      which the U is transformed. Among the microorganisms, algae are of predominant
      interest for the ecological engineer because of their ability to sequester U and
      because some algae can live under many extreme environments, often in abundance.
      Algae grow in a wide spectrum of water qualities, from alkaline environments
      (Chara, Nitella) to acidic mine drainage waste waters (Mougeotia, Ulothrix). If
      they could be induced to grow in waste waters, they would provide a simple, long
      term means to remove U and other radionuclides from U mining effluents. This
      paper reviews the literature on algal and microbial adsorption, reduction, and
      transformation of U in waste streams, wetlands, lakes and oceans.

PMID- 15511558
TI  - Spatial and time variations of radon-222 concentration in the atmosphere of a
      dead-end horizontal tunnel.
AB  - The concentration of radon-222 has been monitored since 1995 in the atmosphere of
      a 2 m transverse dimension, 128 m long, dead-end horizontal tunnel located in the
      French Alps, at an altitude of 1600 m. Most of the time, the radon concentration
      is stable, with an average value ranging from 200 Bq m(-3) near the entrance to
      about 1000 Bq m(-3) in the most confined section, with an equilibrium factor
      between radon and its short-lived decay products varying from 0.61 to 0.78.
      However, radon bursts are repeatedly observed, with amplitudes reaching up to 36
      x 10(3) Bq m(-3) and durations varying from one to several weeks, with similar
      spatial variations along the tunnel as the background concentration. These
      spatial variations are qualitatively interpreted in terms of natural ventilation.
      Comparing the radon background concentration with the measured radon exhalation
      flux at the wall yields an estimate of 8+/-2 x 10(-6) s(-1) (0.03+/-0.007 h(-1))
      for the ventilation rate. The hypothesis that the bursts could be due to
      transient changes in ventilation can be ruled out. Thus, the bursts are the
      results of transient increased radon exhalation at the walls, that could be due
      to meteorological effects or possibly combined hydrological and mechanical
      forcing associated with the water level variations of the nearby Roselend
      reservoir lake. Such studies are of interest for radiation protection in poorly
      ventilated underground settings, and, ultimately, for a better understanding of
      radon exhalation associated with tectonic or volcanic processes.

PMID- 15511559
TI  - Size-fractionated thorium isotopes (228Th, 230Th, 232Th) in surface waters in the
      Jiulong River estuary, China.
AB  - Thorium isotopes (228Th, 230Th, 232Th and 234Th) are useful tracers for studying
      particle dynamics and trace element scavenging in marine environments. In this
      study, surface waters were collected along a salinity gradient from the Jiulong
      River estuary, China, for determination of activity concentrations of 228Th,
      230Th and 232Th in different size fractions, namely, the >53 microm, 10-53
      microm, 2-10 microm, 0.4-2 microm, 10 kDa-0.4 microm and the <10 kDa fractions.
      Our results indicated that the activity concentrations of 228Th, 230Th and 232Th
      in the Jiulong River estuarine waters were significantly higher than most of the
      previously reported values in coastal and oceanic seawaters, suggesting a higher
      lithogenic U and Th contribution from the Jiulong River Basin. When normalized to
      the particulate mass concentration, the activity concentrations of the three
      thorium isotopes decreased with increasing particle size, demonstrating the
      important role of surface areas of particles in controlling the scavenging of
      thorium from the water column. The partitioning of three thorium isotopes showed
      a common characteristic, i.e., the >53 microm fraction had the least share (0
      1%), while the 10-53 microm fraction had the largest share of Th isotopes. The
      average value of the 230Th/232Th activity ratio (230Th/232Th)(A.R.) increased
      from 0.8 in the >53 microm fraction to 3.7 in the 10 kDa-0.4 microm fraction,
      indicating that the radiogenic Th isotopes are preferentially scavenged by the
      small size particles. (230Th/232Th)(A.R.) in the <10 kDa and 10 kDa-0.4 microm
      fractions were similar, however, suggesting a similar chemical composition and/or
      equilibrium partitioning between the low molecular weight and colloidal Th. It
      was very interesting to note that the geochemical behaviors of the three Th
      isotopes were different from each other. Dissolved 228Th had the highest
      concentration in the mid-salinity region, showing a non-conservative behavior
      with additional input. In contrast, dissolved 232Th showed a concave profile,
      indicating a net removal of 232Th during the mixing of fresh water with seawater.
      The behavior of Th isotopes in the <10 kDa fraction followed those in the
      dissolved phases. The difference in geochemical behaviors among three Th isotopes
      was ascribed to their different sources in the estuary.

PMID- 15511560
TI  - A new general dynamic model predicting radionuclide concentrations and fluxes in
      coastal areas from readily accessible driving variables.
AB  - This paper presents a general, process-based dynamic model for coastal areas for
      radionuclides (metals, organics and nutrients) from both single pulse fallout and
      continuous deposition. The model gives radionuclide concentrations in water
      (total, dissolved and particulate phases and concentrations in sediments and
      fish) for entire defined coastal areas. The model gives monthly variations. It
      accounts for inflow from tributaries, direct fallout to the coastal area,
      internal fluxes (sedimentation, resuspension, diffusion, burial, mixing and
      biouptake and retention in fish) and fluxes to and from the sea outside the
      defined coastal area and/or adjacent coastal areas. The fluxes of water and
      substances between the sea and the coastal area are differentiated into three
      categories of coast types: (i) areas where the water exchange is regulated by
      tidal effects; (ii) open coastal areas where the water exchange is regulated by
      coastal currents; and (iii) semi-enclosed archipelago coasts. The coastal model
      gives the fluxes to and from the following four abiotic compartments: surface
      water, deep water, ET areas (i.e., areas where fine sediment erosion and
      transport processes dominate the bottom dynamic conditions and resuspension
      appears) and A-areas (i.e., areas of continuous fine sediment accumulation).
      Criteria to define the boundaries for the given coastal area towards the sea, and
      to define whether a coastal area is open or closed are given in operational
      terms. The model is simple to apply since all driving variables may be readily
      accessed from maps and standard monitoring programs. The driving variables are:
      latitude, catchment area, mean annual precipitation, fallout and month of fallout
      and parameters expressing coastal size and form as determined from, e.g.,
      digitized bathymetric maps using a GIS program. Selected results: the predictions
      of radionuclide concentrations in water and fish largely depend on two factors,
      the concentration in the sea outside the given coastal area and/or adjacent
      coastal areas and the ecological half-life of the radionuclide in the sea.
      Uncertainties in these factors generally dominate all other uncertainties, e.g.,
      concerning the surface water retention time, the settling velocity of the
      particulate fraction, the distribution coefficient regulating the fluxes in
      dissolved and particulate phases, the catchment area influences and the factors
      regulating biouptake and excretion of the radionuclide in fish. This means that
      the conditions in the sea are of paramount importance for the conditions in the
      coastal area, even for relatively enclosed coastal areas. This coastal model may
      be regarded as a tool for testing working hypotheses on the relative roles of
      different processes in different coastal areas. Such information is essential for
      getting realistic expectations of various remedial measures, such as coastal
      dredging discussed in this work.

PMID- 15511561
TI  - Comment on "Radon-222 signatures of natural ventilation regimes in an underground
      quarry [Journal of Environmental Radioactivity 71 (2004) 17-32; 72 (2004) 369
      370]".

PMID- 15511562
TI  - Comparative assessment of natural radioactivity in fallout samples from Patras
      and Megalopolis, Greece.
AB  - Bulk deposition samples were collected simultaneously from two Greek cities,
      Patras and Megalopolis, with different emission sources of natural radioactivity,
      on a monthly basis, during a whole year. Gross beta-activity and 238U- and 232Th
      activities were determined in a total of 95 samples of deposited dust. The
      results were statistically analyzed in order to determine the natural
      radioactivity levels and their variations in the above cities. No significant
      difference was found in deposited dust amount between the two cities, while the
      values of gross beta-, 238U- and 232Th-activities were about 3, 71 and 4 times
      higher in Megalopolis than in Patras, respectively. This was attributed to the
      operation of lignite power plants A and B in the vicinity of the city of
      Megalopolis, while natural radioactivity concentrations in Patras' fallout
      samples were of natural sources.

PMID- 15511563
TI  - Radiocaesium soil-to-wood transfer in commercial willow short rotation coppice on
      contaminated farm land.
AB  - The feasibility of willow short rotation coppice (SRC) for energy production as a
      revaluation tool for severely radiocaesium-contaminated land was studied. The
      effects of crop age, clone and soil type on the radiocaesium levels in the wood
      were assessed following sampling in 14 existing willow SRC fields, planted on
      radiocaesium-contaminated land in Sweden following Chernobyl deposition. There
      was only one plot where willow stands of different maturity (R6S2 and R5S4: R,
      root age and S, shoot age) and clone (Rapp and L78183 both of age category R5S4)
      were sampled and no significant differences were found. The soils differed among
      others in clay fraction (3-34%), radiocaesium interception potential (515-6884
      meq kg(-1)), soil solution K (0.09-0.95 mM), exchangeable K (0.58-5.77 meq kg(
      1)) and cation exchange capacity (31-250 meq kg(-1)). The soil-to-wood transfer
      factor (TF) of radiocaesium differed significantly between soil types. The TF
      recorded was generally small (0.00086-0.016 kg kg(-1)), except for willows
      established on sandy soil (0.19-0.46 kg kg(-1)). Apart from the weak yet
      significant exponential correlation between the Cs-TF and the solid/liquid
      distribution coefficient (R2 = 0.54) or the radiocaesium interception potential,
      RIP (R2 = 0.66), no single significant correlations between soil characteristics
      and TF were found. The wood-soil solution 137Cs concentration factor (CF) was
      significantly related to the potassium concentration in the soil solution. A
      different relation was, however, found between the sandy Trodje soils (CF =
      1078.8 x m(K)(-1.83), R2 = 0.99) and the other soils (CF = 35.75 x m(K)(-0.61),
      R2 =0.61). Differences in the ageing rate of radiocaesium in the soil
      (hypothesised fraction of bioavailable caesium subjected to fast ageing for
      Trodje soils only 1% compared to other soils), exchangeable soil K (0.8-1.8 meq
      kg(-1) for Trodje soils and 1.5-5.8 meq kg(-1) for the other soils) and the
      ammonium concentration in the soil solution (0.09-0.31 mM NH4+ for the Trodje
      soils compared to 0.003-0.11 mM NH4+ for the other soils) are put forward as
      potential factors explaining the higher CF and TF observed for the Trodje soils.
      Though from the dataset available it was not possible to unequivocally predict
      the Cs-soil-to-wood-transfer, the generally low TFs observed point to the
      particular suitability for establishment of SRC on radiocaesium-contaminated
      land.

PMID- 15511564
TI  - A simple model for describing the concentration of 212Pb in the atmosphere.
AB  - The implementation of the Comprehensive Test Ban Treaty is resulting in the
      construction of a world-wide system of 80 monitoring stations that will be able
      to detect air-borne radioactivity, not only from atomic bombs but also from other
      anthropogenic and natural sources. A prototype monitoring station has been
      operating since April 1996 in Vancouver, BC, Canada. This station provides daily
      reports of natural radioactivity, including 7Be and decay products of 220Rn
      (thoron). Data for 212Pb concentrations have been analyzed over a 6-month period.
      The concentration is reduced by rainfall, high wind velocity, and low
      temperatures and it also depends on the wind direction, but atmospheric
      inversions appeared to have little impact. We present a relatively simple model,
      which is easy to use and which offers predictive powers that can be applied to
      other similar environmental situations.

PMID- 15511565
TI  - Mesoscale modelling of radioactive contamination formation in Ukraine caused by
      the Chernobyl accident.
AB  - This work is devoted to the reconstruction of time-dependent radioactive
      contamination fields in the territory of Ukraine in the initial period of the
      Chernobyl accident using the model of atmospheric transport LEDI (Lagrangian
      Eulerian DIffusion model). The modelling results were compared with available
      137Cs air and ground contamination measurement data. The 137Cs atmospheric
      transport over the territory of Ukraine was simulated during the first 12 days
      after the accident (from 26 April to 7 May 1986) using real aerological
      information and rain measurement network data. The detailed scenario of the
      release from the accidental unit of the Chernobyl nuclear plant has been built
      (including time-dependent radioactivity release intensity and time-varied height
      of the release). The calculations have enabled to explain the main features of
      spatial and temporal variations of radioactive contamination fields over the
      territory of Ukraine on the regional scale, including the formation of the major
      large-scale spots of radioactive contamination caused by dry and wet deposition.

PMID- 15511566
TI  - Prompt detection of alpha particles from 210Po: another clue to the origin of
      rock varnish?
AB  - Alpha particles have been measured coming from the surfaces of rocks covered with
      dark red-brown rock varnish, as well as rocks that appear to have little, if any,
      varnish. A pronounced peak at 5.3 MeV indicates the presence of 210Po, a short
      lived natural-radioactive element. Surface activities for 33 samples range from
      0.008 Bq/cm2 to 0.065 Bq/cm2. It is estimated that this nuclide is concentrated
      10(11) times in these paper-thin coatings above its concentration in ground-level
      air. Gamma rays from the decay of 137Cs, a product of testing nuclear weapons
      some 50 years ago, were also detected. Analysis of samples of varnish stripped
      from the rock revealed traces of 239,240Pu and 238Pu. The presence of all of
      these isotopes strongly supports the theory that varnish films derive their
      building blocks from the atmosphere and, with time, all rocks in arid
      environments will become coated.

PMID- 15511567
TI  - Retention and phytoavailability of radioniobium in soils.
AB  - Radioniobium is present in long-lived nuclear waste as a result of the activation
      of zirconium pellets associated with the nuclear fuel. The behaviour of niobium
      (Nb) in the environment and especially its fate in the soil-plant system has not
      been thoroughly investigated so far. In safety assessment of French long-lived
      nuclear waste disposal, data concerning the mobility and the bioavailability of
      Nb in soils are needed as well as general trends of its fate in the specific
      environment around the site of French underground research laboratory. Therefore,
      we investigated the mobility of 95Nb in three different soils typical of the area
      of north-eastern France and its uptake by two plants, rye grass (Lolium perenne
      L.) and winter wheat (Triticum aestivum L.). Soil:solution distribution of 95Nb
      was observed in 1:10 batch experiments with deionized water for a 3-day period.
      Results showed that K(d) values were high (in the order of 10(3) L kg(-1)) and
      were still significantly increasing after 3 days. A mathematical model, fitted to
      describe the decrease of the radioactivity after 3 days, is proposed to calculate
      sorption ratios--SR--(rather than K(d) values as equilibrium was not reached)
      over longer periods. Soil-to-plant concentration ratios (CR) were measured in
      shoots and roots of the two plants after cultivation on two soils spiked with
      (95)Nb (406kBqkg(-1)). Soil-to-root dry weight CR were high (0.30-1.52) and could
      probably be due to efficient uptake into the roots. However, no transfer of Nb to
      plant shoots was detected in any of the soils. Nb is thus a rather immobile
      element in soils and its transfer to plants seems limited to underground parts.
      It would therefore tend to accumulate in surface horizons of soils in case of
      long-term continuous surface release.

PMID- 15511568
TI  - Cosmogenic 7Be deposition in North Wales: 7Be concentrations in sheep faeces in
      relation to altitude and precipitation.
AB  - Beryllium-7 (7Be) is a cosmogenic radionuclide with a half-life of 53.3 days
      produced mostly in the stratosphere by cosmic ray spallation of nitrogen and
      oxygen and entering the lower troposphere by atmospheric circulation processes.
      Most of the nuclide is removed by rainout during precipitation, so given that
      rainfall generally increases with altitude, it was considered probable that 7Be
      deposition would also be greater at higher altitudes. The aim of this study was
      to determine if there is any relationship between 7Be concentrations, altitude
      and precipitation by measuring 7Be activity within sheep faeces. An area of North
      Wales and Northwest England was selected for study, extending from the Dee
      Estuary at sea level to Snowdon at 1065 m. The results obtained showed a
      significant increase in 7Be activity with increasing altitude and precipitation
      consistent with predictions based on the existing literature.

PMID- 15511569
TI  - Thermal reactive hazards of HMX with contaminants.
AB  - In the past, many unexpected runaway accidents occurred in manufacturing
      processes, involving volatile chemical and explosive storage and transportation.
      Incompatible product reactions of high explosives must be carefully considered
      using loss prevention strategies for thermal hazards risk analysis. High
      explosive reactions vary via environmental changes, contact materials, or process
      situations, such as onset temperature and shifts in reaction type when high
      explosives are in contact with contaminants. Therefore, the manufacture and
      handling of high explosives require the utmost in safety and loss prevention. HMX
      (cyclotetramethyene tetranitramine) is one kind of high explosive widely used
      around the world which is stable with high detonation strength properties. In
      this study, the influences of contaminants on HMX are investigated. The studied
      contaminants include ferrous chloride tetrahydrate, ferric chloride hexahydrate,
      acetone solution, acetic acid, and nitric acid. DSC thermal curves and
      incompatible reaction kinetic evaluations were preformed using iron, chlorine and
      acid. Organic acetone solution has lesser effects on HMX. Hopefully, this study
      will lead to improved thermal hazards risk analysis and reduce accidents.

PMID- 15511570
TI  - Social and political amplification of technological hazards. The case of the
      PEPCON explosion.
AB  - Using an industrial explosion in Henderson, Nevada, as a case study, this paper
      examines three main issues: the efficacy of a technological hazard event in
      amplifying otherwise latent issues, the extent to which the hazard event can
      serve as a focusing event for substantive local and state policy initiatives, and
      the effect of fragmentation of political authority in managing technological
      hazards. The findings indicate that the explosion amplified several public safety
      issues and galvanized the public into pressing for major policy initiatives.
      However, notwithstanding the amplification of several otherwise latent issues,
      and the flurry of activities by the state and local governments, the hazard event
      did not seem to be an effective focusing event or trigger mechanism for
      substantive state and local policy initiatives. In addition, the study provides
      evidence of the need for a stronger nexus between political authority, land-use
      planning and technological hazard management.

PMID- 15511571
TI  - Monitoring of toxicity and intermediates of C.I. Direct Black 38 azo dye through
      decolorization in an anaerobic/aerobic sequential reactor system.
AB  - An Upflow Anaerobic Sludge Blanket Reactor/Continuous Stirred Tank Reactor was
      used sequentially to decolorize and mineralize C.I. Direct Black 38 azo dye (3200
      mg/L) in a synthetic wastewater containing glucose as co-substrate. At the steady
      state conditions color was effectively removed under anaerobic condition, while
      the total aromatic amines and organic fraction could be mainly reduced under
      aerobic conditions. NO(3)(-)--N, COD, BOD(5,) aromatic amine, HPLC and GC
      analyses showed that Direct Black 38 could be chiefly mineralized by the
      sequential system. The toxicity levels were determined using three different test
      organism (ATA-anaerobic toxicity, respiration/inhibition and Daphnia magna tests)
      through the continuous operation of anaerobic/aerobic sequential system treating
      Direct Black 38 dye containing synthetic wastewater. Feed and anaerobic effluent
      had greater toxicity than the aerobic effluent after mineralization of dye.

PMID- 15511572
TI  - Retention of fluoride ions from aqueous solution using porous hydroxyapatite.
      Structure and conduction properties.
AB  - Synthetic porous calcium hydroxyapatite (noted p-HAp) treated with different
      fluoride concentrations at room temperature in the presence of carbonate, sodium
      chloride and phosphate-rich media was investigated. The fluoridation rate of the
      porous calcium hydroxyapatite was 89% using 1 mol/L [F(-)] solution compared with
      30% for crystalline hydroxyapatite (c-HAp). The high specific surface area of p
      HAp (235 m(2)g(-1)) compared with c-HAp sample (47 m(2)g(-1)) has an important
      effect on the removal of fluoride ions from aqueous solution, when p-HAp was
      treated with high fluoride concentration to produce calcium fluorohydroxyapatite
      materials. Fluoride adsorption on porous hydroxyapatites (p-HAp) modified their
      structural and conduction properties.

PMID- 15511573
TI  - Removal of copper (II) by manganese-coated sand in a liquid fluidized-bed
      reactor.
AB  - This study was performed in a fluidized-bed reactor (FBR) filled with manganese
      coated sand (MCS) to treat copper-contaminated wastewater. The adsorption
      characteristics of MCS, the adsorption equilibrium of MCS, and the copper removal
      capacity by MCS in FBR were investigated. In terms of the adsorption
      characteristics of MCS, the surface of MCS was evaluated using a scanning
      electron microscope (SEM). Energy dispersive analysis (EDS) of X-rays indicated
      the composition of MCS, and the quantity of manganese on MCS was determined by
      means of acid digestion analysis. The experimental results indicated that copper
      was removed by both sorption (ion exchange and adsorption) and coprecipitation on
      the surface of MCS in FBR. Copper removal efficiency was highly dependent on the
      pH and increased with increasing pH from pH 2 to 8. After the copper adsorption
      by MCS, the pH in solution was decreased. When the MCS concentration was greater
      than 10 g/l, the copper adsorptivities obtained by FBR were almost the same as
      that from the shaker and when the MCS concentration reached 40 g/l, the copper
      adsorptivity in FBR was greater than that from the shaker. The adsorption sites
      of MCS could be used efficiently by the FBR. A Langmuir adsorption isotherm
      equation fit the measured adsorption data from the batch equilibrium adsorption
      test better than the Freundlich adsorption isotherm equation did. In addition,
      the adsorption rate increased when the influent wastewater was aerated.

PMID- 15511574
TI  - Formation of polychlorinated dibenzo-p-dioxins and dibenzofurans on secondary
      combustor/boiler ash from a rotary kiln burning hazardous waste.
AB  - Ash from the secondary combustor/boiler of a rotary kiln burning hazardous
      chemical waste was tested in the laboratory for its potential to form
      polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F). The ash contained
      only a small quantity of "native" PCDD/F, i.e., formed on the ash in the
      facility. However, it produced a considerable amount of these compounds when
      heated in 10% O(2)/N(2) under "de novo" conditions, i.e., with residual carbon
      (present on the ash as result of incomplete combustion) as the only organic
      material. The ash yielded PCDD/F for up to 90 min; gave PCDD/F yields
      proportional to the amount of ash used in the reaction bed; and displayed an
      optimum temperature range for formation (397-548 degrees C) higher than seen for
      most municipal solid waste (MSW) fly ashes. The role of copper and iron as
      catalytic material on the ash is discussed.

PMID- 15511575
TI  - Reduction of metal leaching in brown coal fly ash using geopolymers.
AB  - Current regulations classify fly ash as a prescribed waste and prohibit its
      disposal in regular landfill. Treatment of the fly ash can reduce the leach rate
      of metals, and allow it to be disposed in less prescribed landfill. A geopolymer
      matrix was investigated as a potential stabilisation method for brown coal fly
      ash. Precipitator fly ash was obtained from electrostatic precipitators and
      leached fly ash was collected from ash disposal ponds, and leaching tests were
      conducted on both types of geopolymer stabilised fly ashes. The ratio of fly ash
      to geopolymer was varied to determine the effects of different compositions on
      leaching rates. Fourteen metals and heavy metals were targeted during the
      leaching tests and the results indicate that a geopolymer is effective at
      reducing the leach rates of many metals from the fly ash, such as calcium,
      arsenic, selenium, strontium and barium. The major element leachate
      concentrations obtained from leached fly ash were in general lower than that of
      precipitator fly ash. Conversely, heavy metal leachate concentrations were lower
      in precipitator fly ash than leached pond fly ash. The maximum addition of fly
      ash to this geopolymer was found to be 60wt% for fly ash obtained from the
      electrostatic precipitators and 70wt% for fly ash obtained from ash disposal
      ponds. The formation of geopolymer in the presence of fly ash was studied using
      29Si MAS-NMR and showed that a geopolymer matrix was formed. X-ray diffraction
      (XRD) analysis and scanning electron microscopy (SEM) imaging showed the
      interaction of the fly ash with the geopolymer, which was related to the leachate
      data and also the maximum percentage fly ash addition.

PMID- 15511576
TI  - Separation of H(2)SO(4) + CuSO(4) mixture by diffusion dialysis.
AB  - Diffusion dialysis of aqueous solution of H(2)SO(4) + CuSO(4) has been
      investigated in a two-compartment cell with an anion-exchange membrane Neosepta
      AFN. The experiments have proved that sulfuric acid permeates well through the
      membrane used, while cupric sulfate is efficiently rejected. This operation is
      very effective at high acid concentrations and low concentrations of cupric
      sulfate. Furthermore, it has been found that even at the highest concentration of
      CuSO(4), the rejection coefficient is higher than 0.965. The flux of CuSO(4)
      calculated from the time dependences of the CuSO(4) concentration is negatively
      influenced by increasing acid concentration.

PMID- 15511577
TI  - Leaching of CCA-treated wood: implications for waste disposal.
AB  - Leaching of arsenic, chromium, and copper from chromated copper arsenate (CCA)
      treated wood poses possible environmental risk when disposed. Samples of un
      weathered CCA-treated wood were tested using a variety of the US regulatory
      leaching procedures, including the toxicity characteristic leaching procedure
      (TCLP), synthetic precipitation leaching procedure (SPLP), extraction procedure
      toxicity method (EPTOX), waste extraction test (WET), multiple extraction
      procedure (MEP), and modifications of these procedures which utilized actual MSW
      landfill leachates, a construction and demolition (C and D) debris leachate, and
      a concrete enhanced leachate. Additional experiments were conducted to assess
      factors affecting leaching, such as particle size, pH, and leaching contact time.
      Results from the regulatory leaching tests provided similar results with the
      exception of the WET, which extracted greater quantities of metals. Experiments
      conducted using actual MSW leachate, C and D debris leachate, and concrete
      enhanced leachate provided results that were within the same order of magnitude
      as results obtained from TCLP, SPLP, and EPTOX. Eleven of 13 samples of CCA
      treated dimensional lumber exceeded the US EPA's toxicity characteristic (TC)
      threshold for arsenic (5 mg/L). If un-weathered arsenic-treated wood were not
      otherwise excluded from the definition of hazardous waste, it frequently would
      require management as such. When extracted with simulated rainwater (SPLP), 9 of
      the 13 samples leached arsenic at concentrations above 5 mg/L. Metal leachability
      tended to increase with decreasing particle size and at pH extremes. All three
      metals leached above the drinking water standards thus possibly posing a
      potential risk to groundwater. Arsenic is a major concern from a disposal point
      of view with respect to ground water quality.

PMID- 15511578
TI  - An overview of recycling and treatment of scrap computers.
AB  - In order to recover valuable materials and to minimize the adverse effects of
      hazardous materials contained in scrap computers, a dismantling practice is
      commonly adopted to treat scrap computers. By using the dismantling process, both
      useful and hazardous materials can be manually separated and retrieved. On the
      basis of the properties of the retrieved materials, they can be sent to
      appropriate facilities for further recycling or treatment. Among the retrieved
      materials, the treatment of hazardous materials from cathode ray tubes (CRT) and
      printed circuit boards with integrated circuits have drawn considerable
      attention, thus implying that the proper treatment of such materials can greatly
      assure the successful recycling of scrap computers. For this reason, this study
      reviews the available technologies which can be applied to treat and recycle
      cathode ray tube components and printed circuit boards with integrated circuits.
      Actual recycling data from a scrap computer recycling plant located in Taiwan are
      also introduced. The data show that this recycling plant can recover 94.75 wt. %
      and 45.99 wt. % of useful materials from the main machines (i.e., CPU, power
      supplier, fan, IC boards, DVD drive, CD drive, hard disk, soft disk, shell
      casing, etc.) and monitors of scrap computers, respectively.

PMID- 15511579
TI  - Lead leachability in stabilized/solidified soil samples evaluated with different
      leaching tests.
AB  - Leaching tests and model calculations were performed to investigate the
      immobilization mechanisms of Pb and compare different leaching protocols.
      Stabilization/solidification (S/S) treatments reduced Pb concentrations in the
      toxicity characteristic leaching procedure (TCLP) leachate from 5.9 mg/L for
      untreated soil to less than 0.7 mg/L. The results of eight different leaching
      protocols show that: (1) the main factor controlling the Pb concentration in the
      leachate is the final pH; (2) the final pH is a function of the leachant acidity;
      and (3) for a given final pH, the type of leachant has a relatively minor effect
      on leachability. The diffuse layer adsorption model, aqueous and precipitation
      reactions were employed in the MINTEQA2 program to describe the Pb leaching
      behavior. Both leaching tests and model simulations indicate that the Pb leaching
      behavior can be divided into three stages based on the leachate pH: a high
      alkalinity leaching stage at pH > 12, where Pb formed soluble hydroxide anion
      complexes and leached out; a neutral to alkaline immobilization stage in the pH
      range of 6-12, which was characterized by low Pb leachability caused by
      adsorption and precipitation; and an acid leaching stage with pH < 6, where the
      acid neutralizing capacity (ANC) of the S/S materials was totally consumed and
      therefore free Pb-ion leached out.

PMID- 15511580
TI  - Extraction of phenol from wastewater by N-octanoylpyrrolidine.
AB  - In this paper a new type of phenol extractant, N-octanoylpyrrolidine (OPOD), was
      synthesized. The behavior of phenol of wastewater extraction by N
      octanoylpyrrolidine (OPOD) in kerosene was studied and the dependence of the
      extraction distribution ratios on the concentrations of extractant, phenol,
      acidity and temperature was investigated. The experimental results proved that
      OPOD could extract phenol effectively. The mechanism of the extraction of phenol
      by OPOD was studied in detail.

PMID- 15511581
TI  - Evaluation and optimization of chromium removal from tannery effluent by
      microemulsion in the Morris extractor.
AB  - In this research a surfactant derived from a vegetable oil (coconut oil) was used
      to remove chromium from a tannery effluent. In the extraction process, a Morris
      extractor was used. Important variables used in assessing the optimization of the
      process included agitation speed, solvent rate and total flow rate. The
      experiments were conducted using a 2(3) factorial design. According to the
      response from the experimental design, the effects of each variable were
      calculated and the interactions between them determined. Response surface
      methodology was employed to study the effects of the studied variables. The
      optimum operational conditions were: agitation speed, 428 rpm; solvent rate,
      0.37; total flow rate, 2.0 l h(-1). After extraction process, a re-extraction
      study was accomplished and the obtained results showed that chromium could be
      removed from the microemulsion phase by hydrochloric and sulphuric acidic
      solutions, what allows its reuse in the leather manufacturing process.

PMID- 15511582
TI  - The effect of surfactants on the distribution of organic compounds in the soil
      solid/water system.
AB  - The efficiency of soil remediation by surfactant washing was evaluated via the
      measured distribution coefficients of a number of nonpolar compounds in several
      soil-water mixtures. The studied compounds (contaminants) are BTEX (benzene,
      toluene, ethylbenzene, and p-xylene) and three chlorinated pesticides (lindane,
      alpha-BHC, and heptachlor epoxide), which span several orders of magnitude in
      water solubility (S(w)). A peat, and two natural soils were used that comprise a
      wide range in soil organic matter (SOM) content. The surfactants tested included
      cationic, anionic and nonionic types, with concentrations up to five to six times
      the critical micelle concentration (CMC). The K(d)(*)/K(d), values were used to
      evaluate the remediation efficiency under various operation conditions. For
      relatively water soluble BTEX compounds, the surfactant adsorption on the soil
      surface is the deciding factor on contaminant desorption from soil. For the less
      soluble pesticides, surfactant micelles in solution influence the contaminant
      desorption more. The contaminants partitioning to SOM or adsorbed surfactants
      lowers the desorption efficiency. Anionic surfactants are found to be a better
      choice on soil remediation because they do not form admicelle on soil surface
      that enhances the SOM content. Cationic surfactant, which adsorb onto soil
      surfaces, leads to poor remediation efficiency. An improper selection of
      surfactant would result in inefficiency in soil remediation by surfactant
      washing.

PMID- 15511583
TI  - Removal of phosphate from aqueous solution with blast furnace slag.
AB  - Blast furnace slag was used to remove phosphate from aqueous solutions. The
      influence of pH, temperature, agitation rate, and blast furnace slag dosage on
      phosphate removal was investigated by conducting a series of batch adsorption
      experiments. In addition, the yield and mechanisms of phosphate removal were
      explained on the basis of the results of X-ray spectroscopy, measurements of zeta
      potential of particles, specific surface area, and images of scanning electron
      microscopy (SEM) of the particles before and after adsorption. The specific
      surface area of the blast furnace slag was 0.4m(2)g(-1). The removal of phosphate
      predominantly has taken place by a precipitation mechanism and weak physical
      interactions between the surface of adsorbent and the metallic salts of
      phosphate. In this study, phosphate removal in excess of 99% was obtained, and it
      was concluded that blast furnace slag is an efficient adsorbent for the removal
      of phosphate from solution.

PMID- 15511584
TI  - Hazardous ions uptake behavior of thermally activated steel-making slag.
AB  - This study concerns the utilization of waste steel-making slag, a by-product that
      contains mainly CaO, Fe(2)O(3) and SiO(2). The as-received slag was ground and
      thermally activated by temperature treatment from 110 to 1000 degrees C for 24 h.
      Although the as-received slag was amorphous, it became partially crystallized
      during grinding. These crystalline phases were larnite and iron oxide but other
      crystalline phases also appeared in addition to larnite after calcination. The
      uptake of Ni(2+), PO(4)(3-) and NH(4)(+) by the samples was investigated from
      solutions with initial concentrations of 10 mmol/l. The sample calcined at 800
      degrees C showed the highest Ni(2+) uptake (4.85 mmol/g) whereas the highest
      simultaneous uptake of PO(4)(3-) (2.75 mmol/g) and NH(4)(+) (0.25 mmol/g) was
      achieved by calcining the material at 700 degrees C. The principal mechanism of
      Ni(2+) uptake is thought to involve replacement of Ca(2+) by Ni(2+). The
      mechanism of PO(4)(3-) uptake is mainly by formation of calcium phosphate while
      that of NH(4)(+) involves sorption by the porous silica surface of the samples.

PMID- 15511585
TI  - High temperature removal of hydrogen sulfide using an N-150 sorbent.
AB  - In this study, an N-150 sorbent was used as a high temperature desulfurization
      sorbent for the removal of hydrogen sulfide from coal gas in a fixed bed reactor.
      The results indicate that the N-150 sorbent could be used for H(2)S removal in
      the tested temperature ranges. Regeneration test also reveals that utilization of
      the N-150 sorbent maintains up to 85% compared to the fresh sorbent. No
      significant degeneration occurs on the N-150 sorbent. In addition, various
      concentrations of H(2)S, H(2) and CO were also considered in the performance test
      of the N-150 sorbent. Except for H(2)S, H(2) and CO act the important roles in
      the high temperature desulfurization. By increasing the H(2) concentration, the
      sulfur capacity of the sorbent decreases and an adverse result is observed in the
      case of increasing CO concentration. This can be explained via water-shift
      reaction. On the basis of the instrument analysis, X-ray powder diffraction
      determination and SEM images with EDS spectrum characterization, residual sulfur
      is found in the regenerated N-150 sorbent and this sulfur species is sulfate
      which resulted by incomplete regeneration. The sulfate formation and sintering
      effect are major reasons to cause activity loss in the sulfidation/regeneration
      cycles.

PMID- 15511586
TI  - Evaluation of trickle-bed air biofilter performance for MEK removal.
AB  - A lab-scale trickle-bed air biofilter (TBAB) was operated to evaluate the removal
      of methyl ethyl ketone (MEK) from waste gas. Three biomass control strategies
      were investigated, namely, backwashing and two non-use periods (starvation and
      stagnant). Five volumetric loading rates from 0.70 to 7.04 kg COD/m(3)day were
      employed. Backwashing once a week removed the excess biomass and obtained long
      term, stable performance over 99% removal efficiency for loading rates less than
      5.63 kg COD/m(3)day. The two non-use periods could also sustain 99% removal
      efficiency and could be employed as another means of biomass control for loading
      rates up to 3.52 kg COD/m(3)day. The non-use periods did not delay the recovery
      when the loading rate did not exceed 3.52 kg COD/m(3)day. The pseudo-first-order
      removal rate constant decreased with increase in volumetric loading rate. The
      effect of non-use periods on removal rate showed apparent transition from
      positive to negative with the increase in loading rate.

PMID- 15511587
TI  - Photodegradation of Reactive Black 5, Direct Red 28 and Direct Yellow 12 using
      UV, UV/H(2)O(2) and UV/H(2)O(2)/Fe(2+): a comparative study.
AB  - The photodegradation of three commercially available dyestuffs (C.I. Reactive
      Black 5, C.I. RB5, C.I. Direct Yellow 12, C.I. DY12, and C.I. Direct Red 28, C.I.
      DR28) by UV, UV/H(2)O(2) and UV/H(2)O(2)/Fe(II) processes was investigated in a
      laboratory-scale batch photoreactor equipped with an 16W immersed-type low
      pressure mercury vapour lamp. The experimental results were assessed in terms of
      absorbance and total organic carbon (TOC) reduction. The initial concentration
      was kept constant at 100 mg l(-1) for all dyes. Initial results showed that,
      color removal efficiencies by UV or H(2)O(2) alone were negligible for all dyes.
      Almost complete disappearance of C.I. RB5 (99%) and DY12 (98%) in UV/H(2)O(2)
      process was possible to achieve after 60 min of irradiation. The maximum color
      removal efficiency of C.I. DR28 after 60 min of irradiation, however, was only
      40% and reached a maximum value of 70% after 120 min of irradiation.
      Corresponding mineralization efficiencies were 50, 55 and 7-12%, respectively.
      The addition of Fe(II) to the system, so-called the photo-Fenton process, greatly
      enhanced the color removal, the efficiencies being 98, 88 and 85% for C.I. RB5,
      C.I. DY12 and C.I. DR28 only after 5 min of irradiation. Corresponding
      mineralization efficiencies were 98% for 45 min irradiation, 100% for 60 min
      irradiation and 98% for 90 min irradiation, respectively. However, marginal
      benefit was less significant in the higher range of both H(2)O(2) and Fe(II).
      Furthermore, decreases in both decolorization and mineralization were observed at
      higher concentrations of oxidant and catalyst due to the scavenging effect of
      excess H(2)O(2) and OH radicals. The degradation of all dyes was found to follow
      first-order reaction kinetics.

PMID- 15511588
TI  - Dye adsorption by calcium chloride treated beech sawdust in batch and fixed-bed
      systems.
AB  - Batch and column kinetics of methylene blue and red basic 22 adsorption on
      CaCl(2) treated beech sawdust was investigated, using untreated beech sawdust as
      control, in order to explore its potential use as a low-cost adsorbent for
      wastewater dye removal. The adsorption capacity, estimated according to
      Freundlich's model, and the adsorption capacity coefficient values, determined
      using the Bohart and Adams' bed depth service model indicate that CaCl(2)
      treatment enhanced the adsorption properties of the original material.

PMID- 15511589
TI  - Decolorization of orange II by catalytic oxidation using iron (III)
      phthalocyanine-tetrasulfonic acid.
AB  - Orange II, C.I. Acid Orange 7 (AO7), is oxidatively decolorized via catalytic
      oxidation by iron(III) phthalocyanine-tetrasulfonic acid (Fe(III)-PcTS) as a
      biomimetic catalyst and KHSO(5) as an oxygen donor. The nature of the
      decolorization of AO7 was investigated in the catalyst concentration range of 10
      50 microM, in which the initial concentration of AO7 was 417 mg l(-1). A 99.6%
      decolorization was observed at [KHSO(5)] = 2.5 mM and [Fe(III)-PcTS] = 20 microM
      after a 3-h reaction period. However, the fact that only 4.9% of the TOC was
      removed indicated that the conversion to CO(2) was incomplete. The results of a
      total organic nitrogen analysis of the reaction mixture showed that the nitrogen
      in the azo chain was mainly converted to N(2) gas. In addition, 38.6% of the AO7
      was converted to 1,2-dihydroxynaphthalene, and 21.4% to p-phenolsulfonic acid.
      These results indicate that the degradation via this catalytic system involves
      the conversion of AO7 to phenolic compounds, followed by N(2) production. In
      addition, a Microtox test showed that toxicity of the solution increased as a
      result of AO7 oxidation using this catalytic system.

PMID- 15511590
TI  - Capability of coupled CdSe/TiO(2) for photocatalytic degradation of 4
      chlorophenol.
AB  - The photocatalytic process using TiO(2) and coupled semiconductor in the
      photodegradation reaction of 4-chlorophenol (4-CP) was investigated. Nanosized
      titanium dioxide powder was synthesized via the sol-gel procedure and modified
      via the coupled photocatalysts. The microstructural and chemical properties of
      TiO(2) and coupled CdSe/TiO(2) were also examined. For CdSe/TiO(2) samples, the
      specific surface area was 7.0 m(2)/g and the deposition proportion of CdSe was
      approximately 27.6%. In the photocatalysis results, higher photodegradation
      efficiency of 4-CP was observed at higher pH values. In the UV 254 nm system, the
      degradation efficiency of 4-CP and TOC with sol-gel produced TiO(2) (TiO(2)(SG))
      powder was higher than with commercial TiO(2)(RdH) powder. For the coupled
      semiconductor system (CdSe/TiO(2)), the apparent first-order rate constants were
      1.35 x 10(-2), 4.33 x 10(-2), 2.0 x 10(-3) and 1.9 x 10(-3)min(-1) at the
      conditions of pH 7 (254 nm), pH 11 (254nm), pH 7 (365 nm), and pH 11 (365 nm).
      The disappearance of 4-CP under CdSe/TiO(2)(RdH) photoreaction at pH 7 and 365 nm
      condition is better than that of TiO(2)(RdH) system, with 30% versus 22% 4-CP
      reduction in 180 min. In the same condition, CdSe/TiO(2)(RdH) provided more
      photomineralization efficiency than that of TiO(2)(RdH) in terms of TOC
      reduction. Both 4-CP and TOC reduction were significant for systems illuminated
      at 254 nm. Considering the direct photolysis effect at 254 nm where 4-CP
      reduction is near 100% and TOC removal is nil, CdSe/TiO(2)(RdH) exhibits a 50%
      photomineralization efficiency and a nearly four times faster reaction rate than
      the single TiO(2)(RdH) semiconductor.

PMID- 15511591
TI  - Photodegradation of polychlorinated dibenzo-p-dioxins: comparison of
      photocatalysts.
AB  - 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin (1,2,3,6,7,8-HxCDD) and octachlorodibenzo
      p-dioxin (OCDD) were photocatalytically degraded using immobilized TiO(2), ZnO
      and SnO(2) films under ultraviolet (UV) with the wavelength between 300 and 450
      nm. The specific surface areas of TiO(2), ZnO and SnO(2) powders were calculated
      as 54.2, 4.6 and 4.8 m(2)/g, and the band gap energies were determined to be
      3.17, 2.92 and 4.13 eV, respectively. The light source used had wavelengths
      between 300 and 450 nm, and the main wavelength was approximately 365 nm; hence,
      the smaller quantum efficiency of SnO(2) with wider band gap due to poor
      utilization of the UV light was expected. X-ray diffraction (XRD) revealed that
      sintered photocatalysts at 400 degrees C did not alter their characteristics. The
      first-order rate constants of OCDD in UV/TiO(2), UV/ZnO and UV/SnO(2) were 5.30,
      0.74 and 0.28 h(-1), respectively; those of 1,2,3,6,7,8-HxCDD in UV/ZnO and
      UV/SnO(2) were 3.28 and 3.19 h(-1), respectively. As expected, photodegradation
      rates declined as the number of chlorine atoms increased. Due to the low dosage
      (50 ng) of target compounds used, the amounts of Cl(-) and total organic carbon
      were too small for quantification. No 2,3,7,8-substituted congeners was
      identified during the photodegradation, and the UV/photocatalyst treatment might
      offer an effective treatment for PCDDs.

PMID- 15511592
TI  - Fundamentals, present and future perspectives of electrocoagulation.
AB  - Electrocoagulation is an electrochemical wastewater treatment technology that is
      currently experiencing both increased popularity and considerable technical
      improvements. There has been relatively little effort to better understand the
      fundamental mechanisms of the processes, particularly those that could provide
      design parameters to optimize the performances of this relatively simple and
      inexpensive technique. In a research programme to delineate the mechanisms of the
      fundamental processes involved in, the authors have realized that the technology
      has been insufficiently reviewed with emphasis on the fundamentals and their
      relationship to the performance of this technology. This paper presents an in
      depth discussion and consideration of the factors that need to be addressed for
      optimum performance of this technology. Recent improvements of this technique and
      the theoretical model studies are also reviewed.

PMID- 15511593
TI  - Advances in encapsulation technologies for the management of mercury-contaminated
      hazardous wastes.
AB  - Although industrial and commercial uses of mercury have been curtailed in recent
      times, there is a demonstrated need for the development of reliable hazardous
      waste management techniques because of historic operations that have led to
      significant contamination and ongoing hazardous waste generation. This study was
      performed to evaluate whether the U.S. EPA could propose treatment and disposal
      alternatives to the current land disposal restriction (LDR) treatment standards
      for mercury. The focus of this article is on the current state of encapsulation
      technologies that can be used to immobilize elemental mercury, mercury
      contaminated debris, and other mercury-contaminated wastes, soils, sediments, or
      sludges. The range of encapsulation materials used in bench-scale, pilot-scale,
      and full-scale applications for mercury-contaminated wastes are summarized.
      Several studies have been completed regarding the application of sulfur polymer
      stabilization/solidification, chemically bonded phosphate ceramic encapsulation,
      and polyethylene encapsulation. Other materials reported in the literature as
      under development for encapsulation use include asphalt, polyester resins,
      synthetic elastomers, polysiloxane, sol-gels, Dolocrete, and carbon/cement
      mixtures. The primary objective of these encapsulation methods is to physically
      immobilize the wastes to prevent contact with leaching agents such as water.
      However, when used for mercury-contaminated wastes, several of these methods
      require a pretreatment or stabilization step to chemically fix mercury into a
      highly insoluble form prior to encapsulation. Performance data is summarized from
      the testing and evaluation of various encapsulated, mercury-contaminated wastes.
      Future technology development and research needs are also discussed.

PMID- 15511594
TI  - Adsorption effect of aqueous bichlorobiphenyls onto UV-illuminated titanium
      dioxide.
AB  - Bichlorobiphenyls were adsorbed onto TiO(2) (Degussa P25) in batch equilibrium
      experiments. The results demonstrated that a triple-layer model (TLM) surface
      complex formation model described the adsorption of chlorobiphenyls onto the
      surface of the TiO(2) solid. The surface complex configuration and the adsorption
      reaction may have followed the equation derived from the TLM, involving the loss
      of a proton during the adsorption process. This dependence indicates that the
      oxidation reaction between surface-adsorbed substrates and photogenerated
      oxidants dominates. Both sorbed and dissolved components contribute to the
      observed degradation rate, that is, the 4,4'-CBP degradation rates might be
      stated as linear functions of the sorbed and dissolved concentrations. The
      contribution of the concentration of solution phase in degradation pathways is
      not negligible.

PMID- 15511595
TI  - Adsorption of zinc on bed sediment of River Hindon: adsorption models and
      kinetics.
AB  - The paper presents a study of zinc adsorption using the experimental data on bed
      sediments of River Hindon in western Uttar Pradesh (India). The effect of various
      operating variables, viz., initial concentration, solution pH, sediment dose,
      contact time, and particle size, have been studied. The optimum contact time
      needed to reach equilibrium was of the order of 60 min and was independent of
      initial concentration of zinc ions. The extent of adsorption increased with an
      increase of pH. Furthermore the adsorption of zinc increases with increasing
      adsorbent doses and decreases with the adsorbent particle size. The content of
      iron, manganese and organic matter in various fraction of sediment decreases with
      increasing particle size indicating the possibility of the two geochemical phases
      to act as the active support material for the adsorption of zinc ions. The
      adsorption data follows both Langmuir and Freundlich adsorption models. Isotherms
      were used to determine thermodynamic parameters, viz., free energy change,
      enthalpy change and entropy change. The negative values of free energy change
      indicate spontaneous nature of the adsorption while positive values of enthalpy
      change suggest the endothermic nature of the adsorption of zinc on bed sediment
      of the River Hindon. The positive values of entropy change indicate randomness at
      the solid/solution interface.

PMID- 15511596
TI  - Comment on "Sorption of basic dyes from aqueous solution by activated sludge" [J.
      Hazard. Mater. 108 (2004) 183-188].

PMID- 15511597
TI  - Stress hormones and human memory function across the lifespan.
AB  - In this paper, we summarize the data obtained in our laboratory showing the
      effects of glucocorticoids on human cognitive function in older adults, young
      adults and children. We first present data obtained in the aged human population
      which showed that long-term exposure to high endogenous levels of glucocorticoids
      is associated with both memory impairments and a 14% smaller volume of the
      hippocampus. We then report on studies showing that in older adults with moderate
      levels of glucocorticoids, memory performance can be acutely modulated by
      pharmacological manipulations of glucocorticoids. In young adults, we present
      data obtained in our laboratory showing that cognitive processing sustained by
      the frontal lobes is also sensitive to acute increases of glucocorticoids. We
      also summarize studies showing that just as in older adults, memory performance
      in young adults can be acutely modulated by pharmacological manipulations of
      glucocorticoids. We then present a study in which we showed a differential
      involvement of adrenergic and glucocorticoid hormones for short- and long-term
      memory of neutral and emotional information. In the last section of the paper, we
      present data obtained in a population of young children and teenagers from low
      and high socioeconomic status (SES), where we showed that children from low SES
      present significantly higher levels of basal cortisol when compared to children
      from high SES. We then present new data obtained in this population showing that
      children and teenagers from low and high SES do not process the plausibility of
      positive and negative attributes in the same way. Children from low SES tended to
      process positive and negative attributes on a more negative note than children
      from high SES, and this type of processing was significantly related to basal
      cortisol at age 10, 12 and 14. Altogether, the results of these studies show that
      both bottom-up (effects of glucocorticoids on cognitive function), and top-down
      (effects of cognitive processing on glucocorticoid secretion) effects exist in
      the human population.

PMID- 15511598
TI  - Circulating ghrelin is decreased in non-obese and obese women with binge eating
      disorder as well as in obese non-binge eating women, but not in patients with
      bulimia nervosa.
AB  - Ghrelin is a peripheral gastric peptide involved in the regulation of eating
      behavior and energy homeostasis. While changes in ghrelin plasma levels have been
      found in anorexia nervosa, bulimia nervosa (BN) and obesity, no study has
      assessed circulating ghrelin in binge eating disorder (BED). Therefore, we
      measured plasma levels of this peptide in women with BED as compared to women
      with BN, obesity and healthy controls. One hundred and eighty-two drug-free women
      (56 bulimics, 13 non-obese and 34 obese BED subjects, 28 obese non-binge eating
      women and 51 non-obese healthy women) underwent psychopathological and
      nutritional assessments and blood sample collection for glucose and ghrelin
      assays in the morning. As compared to non-obese healthy women, both non-obese and
      obese BED women as well as obese non-binge eating women had significantly
      increased values of body weight, body mass index and body fat mass. Moreover,
      plasma ghrelin concentrations were significantly decreased in both non-obese
      (P<0.01) and obese (P<0.0001) BED women as well as in obese non-binge eating
      women (P<0.001) but not in women with BN. No significant correlations emerged
      between plasma ghrelin values and the frequency of binge/vomiting in BN subjects
      or the frequency of bingeing in BED individuals. The reduction of plasma ghrelin
      in non-obese and obese binge eaters as well as in obese non-binge eaters may
      represent a secondary change aiming to counteract their positive energy
      imbalance.

PMID- 15511599
TI  - Chronic estrogenic drug treatment increases preproenkephalin mRNA levels in the
      rat striatum and nucleus accumbens.
AB  - Estrogens modulate the expression of preproenkephalin (PPE) in the hypothalamus
      but little is known for other brain regions. The present study investigated the
      effect of hormonal withdrawal and replacement therapy on PPE expression in the
      striatum, nucleus accumbens and cortex. Ovariectomized Sprague-Dawley rats were
      treated for 2 weeks with estradiol, a specific ligand for estrogen receptor alpha
      (ERalpha), 4,4',4''-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT) and
      estrogen receptor beta (ERbeta) 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN), or
      the selective estrogen receptor modulators (SERMs) tamoxifen and raloxifene.
      Brain PPE mRNA levels, measured by in situ hybridization, were high in the
      striatum and nucleus accumbens compared to the low expression in the cortex.
      Ovariectomy decreased uterine weights compared to intact uterus, which was
      corrected by estradiol and PPT. Tamoxifen and raloxifene partially stimulated
      uterine weights while DPN left it unchanged. In the anterior, median and
      posterior striatum and in the core and shell of the nucleus accumbens,
      ovariectomy decreased PPE mRNA levels compared to intact rats, this was corrected
      by estradiol treatment except for the posterior striatum. PPT, DPN, tamoxifen and
      raloxifene reproduced the estradiol effect. In the prefrontal and cingulate
      cortices, neither ovariectomy nor treatments changed PPE mRNA levels. These
      results show for the first time that estradiol increases PPE mRNA in the striatum
      and nucleus accumbens. This effect is observed also with estrogen receptor
      agonists for the ERalpha and ERbeta as well as with SERMs.

PMID- 15511600
TI  - State and trait affect as predictors of salivary cortisol in healthy adults.
AB  - We measured affect in 334 healthy adults on each of 7 days over a 3-week period.
      On the last day, salivary cortisol was assessed 14 times yielding scores for
      total concentration, morning rise amplitude, and slope of the time function.
      Trait negative affect (NA) was associated with higher total cortisol
      concentrations and greater morning rise in men. Cortisol levels for men low in
      trait positive affect (PA) did not decrease in the afternoon, resulting in a
      relatively high, flat rhythm. In contrast, women high in trait PA had low morning
      cortisol resulting in a low flat rhythm. State (person-centered) NA was not
      associated with same-day cortisol measures. State PA was associated with
      decreased total cortisol concentration in women. These are the first results
      showing associations between cortisol and trait PA. Differences in rhythmicity
      found here are noteworthy given the possible role of cortisol dysregulation in
      disease incidence, morbidity, mortality, and severity.

PMID- 15511601
TI  - Tamoxifen fails to affect central serotonergic tone but increases indices of
      anxiety in female rhesus macaques.
AB  - The selective estrogen receptor modulator (SERM), tamoxifen, effectively slows
      the progression of estrogen-positive breast cancer and aids in the prevention of
      cancer in at-risk women. Tamoxifen is well characterized with regards to its
      effects on breast cancer, but its effects on other estrogen-related systems,
      particularly neural circuits regulating brain function and mood, are poorly
      understood. Using ovariectomized rhesus monkeys, we examined the effects of
      tamoxifen, with and without estrogen replacement therapy (ERT), on social
      behavior and central serotonin (5HT) systems thought to influence these
      behaviors. Relative to placebo treatments, estrogen treatment increased
      serotonergic tone, based on response in prolactin and cortisol to fenfluramine, a
      5HT releasing agent. Tamoxifen neither blocked nor enhanced this effect,
      indicating it to be neither an antagonist nor an agonist on serotonergic
      activity. In contrast, CSF measures of the 5HT metabolite, 5HIAA, were not
      significantly affected by treatment. Tamoxifen-treated animals showed increases
      in measures of anxiety, compared with ERT-treated animals, suggesting that this
      SERM may be anxiogenic. Co-treatment with estrogen attenuated the anxiogenic
      properties of tamoxifen. These data show that tamoxifen administration increased
      anxiety levels, but the affect was not associated with differences in central
      levels of the serotonin tone.

PMID- 15511602
TI  - Reproductive events modify the effects of estrogen replacement therapy on
      cognition in healthy postmenopausal women.
AB  - The question of whether estrogen replacement therapy (ERT) is beneficial to
      cognitive functioning in postmenopausal women has become controversial in the
      past several years. Early studies suggested that ERT improved cognitive
      functioning and decreased the risk of Alzheimer's disease, but recent studies
      have failed to find any benefit. However, studies have varied in terms of the age
      of participants, the estrogen preparation used, whether progesterone is
      administered concurrently, and the study design. The present study used a
      randomized, placebo-controlled design and a transdermal estrogen preparation
      composed of 17-beta estradiol. A neuropsychological battery was administered at
      baseline and after completion of the 10-week trial, and test scores were grouped
      into four composite scores using psychometric techniques. Baseline to follow-up
      change was analyzed using multiple regression techniques. Results indicate that
      while little overall beneficial effect of estrogen was found, years since
      menopause was significantly related to change in executive functioning in the
      estrogen but not the placebo group, such that more recently postmenopausal women
      demonstrated greater positive change than older women. Body mass index, a gross
      estimate of circulating estrogen, was significantly positively related to change
      in attentional and psychomotor processes regardless of treatment group, and to a
      weaker extent, verbal memory, but only in the estrogen-treated group. These
      results suggest that reproductive events and levels of endogenous estrogen are
      related to the clinical response to ERT, but larger studies with longer follow-up
      periods are needed to determine the strength of these effects.

PMID- 15511603
TI  - Glucocorticoid receptor polymorphisms and post-traumatic stress disorder.
AB  - Post-traumatic stress disorder (PTSD) is reported in some studies to be
      associated with increased glucocorticoid (GC) sensitivity. Two common
      glucocorticoid receptor (GR) polymorphisms (N363S and BclI) appear to contribute
      to the population variance in GC sensitivity. There is some evidence that there
      may be a genetic predisposition to PTSD. Hence we studied 118 Vietnam war
      veterans with PTSD for (i) GR polymorphisms, particularly the N363S and the BclI
      polymorphisms which are thought to be GC sensitising, and (ii) two measures of GC
      sensitivity, the low-dose 0.25 mg dexamethasone suppression test (LD-DST) and the
      dermal vasoconstrictor assay (DVVA). The DST and GR polymorphisms were also
      performed in 42 combat exposed Vietnam war veterans without PTSD. Basal plasma
      cortisol levels were not significantly different in PTSD (399.5+/-19.2 nmol/L,
      N=75) and controls (348.6+/-23.0 nmol/L, N=33) and the LD-DST resulted in similar
      cortisol suppression in both groups (45.6+/-3.2 vs. 40.8+/-4.1%). The cortisol
      suppression in PTSD patients does not correlate with Clinician Administered PTSD
      Scores (CAPS), however there was a significant association between the BclI GG
      genotype and low basal cortisol levels in PTSD (P=0.048). The response to the
      DVVA was similar to controls (945+/-122, N=106 vs. 730+/-236, N=28, P=0.42). PTSD
      patients with the GG genotype, however, tended to be more responsive to DVVA and
      in this group the DVVA correlated with higher CAPS scores. The only exon 2 GR
      polymorphisms detected were the R23K and N363S. Heterozygosity for the N363S
      variant in PTSD, at 5.1% was not more prevalent than in other population studies
      of the N363S polymorphism in Caucasians (6.0-14.8%). The GG genotype of the BclI
      polymorphism found to be associated with increased GC sensitivity in many studies
      showed a tendency towards increased response with DVVA and correlated with higher
      CAPS scores. In conclusion, the N363S and BclI GR polymorphisms were not more
      frequent in PTSD patients than controls and reported population frequencies. Our
      PTSD group did not display GC hypersensitivity, as measured by the LD-DST and
      DVVA. In a subset of PTSD patients with the BclI GG genotype, CAPS scores and
      basal cortisol levels were negatively correlated.

PMID- 15511604
TI  - Osteoporosis and biomaterial osteointegration.
AB  - Biomaterial osteointegration depends not only on the properties of the implanted
      material but also on the characteristics and regenerative capability of the host
      bone. For this reason, researchers involved in biomaterial evaluation now place
      great importance on the various pathologies often present in orthopaedic patients
      which can negatively affect the success of surgical implants. Osteoporosis is
      undoubtedly one of the most frequently encountered of such diseases. Models
      reproducing the osteoporotic condition can be useful to understand the influence
      of the pathology on cell behaviour, bone regeneration and osteointegration
      processes, thus increasing our basic knowledge and allowing the development of
      surgical techniques and implant biomaterials more suitable for use in the
      surgical treatment of fractures in osteoporotic patients. The present paper is a
      literature review and, after a short description of how the presence of
      osteoporosis could influence bone regenerative processes, the results of the main
      studies on biomaterial biocompatibility and osteointegration both in vitro and in
      vivo in the presence of osteoporotic condition are reported. Both cell cultures
      and animal models are able to demonstrate the different response of bone to
      biomaterials by comparing healthy and pathological conditions. The use of
      pathological bone-derived cells and pathological animals is therefore recommended
      to test candidate orthopaedic materials.

PMID- 15511605
TI  - Different diagnostic techniques for the assessment of cortical bone on
      osteoporotic animals.
AB  - The aim of this study was to assess the capability of ultrasonography and
      densitometry to predict the mechanical competence of cortical bone in healthy and
      osteopenic rats, respectively. Thirty 10-month-old Sprague-Dawley retired breeder
      female rats were used and randomized into three groups of 10 animals each. A
      group underwent bilateral ovariectomy by dorsal approach (Ovx), another group
      underwent a simulated ovariectomy (Sham-Ovx), and the last group served as a sham
      aged control group (Control). Sixteen weeks after surgery, the animals were
      euthanized and the femurs of each rat excised for ultrasonographic and
      densitometric measurements, and mechanical analyses. The Ovx Group had a
      significantly decreased amplitude dependent speed of sound (AD-SoS-about 7-8%)
      when compared to the other groups (p<0.0005). For Ovx animals compared with Sham
      Ovx and Control rats, significant decreases in densitometric data were observed
      (6-13%), as well as significant decreases in femoral Max. Load (about 18%) and
      flexural rigidity (about 30%). The best correlation (R2=0.55, p<0.0005) found was
      between SoS and femoral shaft bone mineral density (SBMD). The regression
      coefficient R2 increased when power-law fits were used, particularly from 0.34
      (p<0.001) to 0.36 (p<0.0005) in the correlation between SoS and Max. Load and
      from 0.21 (p<0.05) to 0.25 (p<0.01) in the correlation between SBMD and Max.
      Load. The ability of QUS or DXA to accurately predict the actual mechanical
      characteristics of bone, and in particular bone elasticity, remained relatively
      poor and the improvement of the power-law model did not describe exhaustively the
      relationships between the variables tested. The DXA and QUS capability to
      discriminate between ovariectomized and non-ovariectomized rats did not improve
      when tested together.

PMID- 15511606
TI  - Glucocorticoid-induced osteoporosis.
AB  - Glucocorticoids are important drugs in the treatment of variety diseases, but
      long-term period use can lead to various adverse effects, including osteoporosis.
      Glucocorticoid-induced osteoporosis is mainly caused by inhibition of
      osteoblastic bone formation, which results not only in decreased bone mineral
      density, but reduction of bone strength by trabecular thinning in bone
      microstructures. The evidence suggests that daily oral glucocorticoid doses
      higher than 5 mg prednisolone or equivalent increase the risk of fracture within
      3-6 months after the start of therapy. High-dose inhaled glucocorticoids may also
      increase fracture risk. The diagnostic procedures are similar to those for
      primary osteoporosis, but the diagnostic threshold for bone mineral density needs
      to be higher than that for primary osteoporosis. Treatment with vitamin D,
      calcitonin, sex hormone replacement, and bisphosphonates has been shown to be
      effective, and bisphosphonates have been demonstrated to be the most valuable
      drugs for glucocorticoid-induced osteoporosis. There are several lines of
      evidence indicating that they are effective in preventing and treating low bone
      mineral density and in reducing fracture risk.

PMID- 15511607
TI  - Osteopenia and osteoporosis in HIV+ patients, untreated or receiving HAART.
AB  - In the last few years there are increasing evidences suggesting that osteopenia
      and osteoporosis are frequent among HIV positive patients. It is still not clear
      if the bone demineralization is a direct consequence of viral infection or of the
      antiretroviral drugs. Studies to date therefore give conflicting results. We
      performed a study to evaluate the prevalence of osteopenia and osteoporosis in
      HIV positive patients, either untreated or receiving antiretroviral therapy, to
      asses the frequency of these conditions and the role of antiretroviral drugs.

PMID- 15511608
TI  - Reverse genetics studies of attenuation of the ca A/AA/6/60 influenza virus: the
      role of the matrix gene.
AB  - The matrix (M) gene of influenza virus has been implicated in the attenuation
      phenotype of the cold adapted (ca) A/AA/6/60 vaccine. Previous studies have
      evaluated the ca M from A/AA/6/60 in different wild type (wt) virus backgrounds
      with varying results. In experiments described here, the ca M gene was
      transfected into the background of its own wt A/AA/6/60 to eliminate the
      possibility of confounding gene constellation effects. Comparison of the sequence
      of the wt and the ca A/AA/6/60 revealed one substitution in the nucleotide
      sequence of M. The molecular techniques of reverse genetics were used to rescue
      the ca M gene into the virulent wt A/AA/6/60 virus. The selection system used to
      identify the desired transfectant virus was amantadine resistance, which was
      introduced into the M2 gene using mutagenesis. The ca A/AA/6/60, the wt
      A/AA/6/60, a virus which contained wt M and was wt in the remaining seven genes
      and amantadine resistant (wt/969), a virus which contained the ca M but wt in the
      other seven genes (ca/969) were all evaluated in mice determine the effect of the
      ca M. The ca/969 virus was not attenuated in the mouse model when compared to the
      wt/969 virus, indicating that the ca A/AA/6/60 M does not independently
      contribute to the attenuation phenotype attributed to the ca A/AA/6/60 vaccine
      virus.

PMID- 15511609
TI  - Blood oxidative stress status in patients with macrophagic myofasciitis.
AB  - The study aimed at determining the presence of an oxidative stress in patients
      with macrophagic myofasciitis (MMF), a new inflammatory myopathy with suspected
      toxic etiology related to aluminium hydroxide-containing vaccines. A total of 30
      MMF patients (nine males, 21 females; aged 42+/-14 years), whose diagnosis was
      confirmed by deltoid biopsy, have been included and compared to 38 sex- and age
      matched healthy control subjects (10 males, 28 females; aged 43+/-8 years). The
      blood oxidative stress status has been evaluated by assaying six parameters:
      plasma lipid peroxidation products (thiobarbituric acid-reactive substances:
      TBARS) and antioxidant defense systems: plasma vitamin E and glutathione
      peroxidase (GSH-Px) activity, erythrocyte GSH-Px and Cu,Zn-superoxide dismutase
      (SOD) activities. Plasma selenium was also determined as a trace element
      essential to the activity of GSH-Px. Statistical significance was evaluated by
      the Mann-Whitney test. Plasma GSH-Px activity, selenium and vitamin E
      concentration were significantly lower in MMF group than in controls (P=0.004,
      P=0.003 and P=0.009, respectively), with a positive correlation in MMF patients
      between plasma GSH-Px activity and selenium concentration (rho=0.0001). The other
      parameters of oxidative stress did not significantly differ between both groups.
      A macrophage activation could occur in MMF, consequently to chronic stimulation
      by aluminium-containing vaccines, and could participate to the lower values of
      selenium and vitamin E observed in comparison with controls. Nevertheless, since
      no deficiency in these elements has been observed, no supplementation is to be
      considered.

PMID- 15511610
TI  - In vitro reversal MDR of human carcinoma cell line by an antisense
      oligodeoxynucleotide-doxorubicin conjugate.
AB  - A conjugate of antisense oligodeoxynucleotide (AS ODN) covalently linked with
      deoxorubicin (DOX) was synthesized. Its properties and antitumour activity in
      human carcinoma DOX resistant cells (KB-A-1) were investigated in vitro. The
      results showed that the conjugate was strongly stable both in Dulbecco's
      Phosphate-Buffered Saline (PBS) and in culture medium. The intracellular
      concentration of the conjugate was higher than that of the AS DON by HPLC
      analysis. The conjugate showed potent dose-dependent inhibition to the growth of
      KB-A-1 cells. Chemosensitivity of KB-A-1 cells to DOX was also investigated in
      vitro. When the cells were first exposed to the conjugate (0.5 microM) and then
      exposed to DOX for 24 h, the IC50 value of DOX decreased from 21.5 to 2.2 microM.
      In contrast, when treated with the mixture of the same concentration of the AS
      ODN with equivalent DOX, the IC50 value of DOX was 16.8 microM. Intracellular DOX
      concentration was detected in KB-A-1 treatment with the conjugate in vitro by
      HPLC. The results showed that the intracellular DOX concentration was 6.4-fold
      increased in KB-A-1 cells treated with the conjugate compared to treatment with
      DOX alone. In contrast, 1.8-fold increasing was observed when treated with the AS
      ODN. Western blot analysis showed a significantly decrease in the amount of P
      glycoprotein in KB-A-1 cells. These results suggest that the conjugate is
      effective in reversing multidrug resistance. Certainly, further studies are
      conducting to explore the antitumour effect of the conjugate in vivo.

PMID- 15511611
TI  - Modulation of the primary and the secondary antibody response by tobacco smoke
      condensates.
AB  - Cigarette smoke condensate administered to C57BL/6 mice led to a decrease in the
      primary antibody response to OVA (hen egg albumin) antigen. Selenium (Se)
      supplementation allowed to relieve significantly this inhibition. Moreover, even
      being not supplemented with Se, a preparation was found devoid of inhibitory
      effects. Furthermore, the presence of Se-supplemented tobacco smoke condensate at
      the time of antigen priming, contributed to an enhanced secondary antibody
      response.

PMID- 15511613
TI  - Current and future commitment to hematology research.
AB  - This article provides an overview of the National Heart Lung and Blood
      Institute's (NHLBI) current and future commitment to hematology research. The
      paper comprises nine sections: (1) a brief history of how NHLBI incorporated
      blood research in its mission; (2) a summary of the traditional areas of research
      interest for blood diseases and resources; (3) a description of how NHLBI has
      assured and continues to assure a safe blood supply; (4) the current and future
      plans for transfusion medicine and cellular therapy research; (5) research
      support for hemoglobinopathies and red cell disorders; (6) research support for
      thrombosis and hemostatic disorders; (7) current and future research of
      hematopoietic stem cell biology, and aplastic and preneoplastic conditions; (8)
      future training for hematologists, and (9) a concluding summary.

PMID- 15511614
TI  - Health-related quality of life assessment in hematologic disease.
AB  - Evaluating health-related quality of life (HRQL) for children who have benign
      hematologic disorders can: (1) aid in the evaluation of different therapies and
      emerging new technologies; (2) serve as an invaluable source of anticipatory
      guidance, for current and future patients; and (3) serve an important evaluative
      function of clinical services or programs to identify potential areas in which
      additional services, supports, or interventions are needed. The past 20 years
      have been marked by the dramatic growth in the field of HRQL research, although
      much of the progress in conceptualization, instrument development, and refinement
      has occurred in adults. Pediatric health services researchers and their clinical
      colleagues have had to grapple with the methodologic challenges in evaluating
      HRQL in children. This article includes a discussion of instrumentation,
      respondent selection, and study design consideration in the evaluation of HRQL in
      children who have benign hematologic disorders.

PMID- 15511615
TI  - Recent advances in the management of the child who has hemophilia.
AB  - This article discusses recent advances in the management of the child who has
      hemophilia.

PMID- 15511616
TI  - Diagnosis and treatment of von Willebrand disease.
AB  - Von Willebrand disease (VWD) is the most common bleeding disorder; it is believed
      to occur in approximately 1% to 2% of the population. Mucocutaneous and surgical
      hemorrhage in affected individuals is caused by quantitative and qualitative
      defects in von Willebrand factor (VWF), a large, multimeric protein that supports
      platelet adhesion and aggregation in the initiation of hemostasis at the time of
      vascular injury and functions as a carrier protein for factor VIII in the
      circulation. Advances in cellular and molecular biology have led to improved
      understanding of the pathophysiology of the disorder and development of a
      classification scheme that is based on quantitative and qualitative defects.
      Effective treatment is dependent on an accurate diagnosis using specific assays
      of VWF that define the various defects.

PMID- 15511617
TI  - The pros and cons of drug therapy for immune thrombocytopenic purpura in
      children.
AB  - This article discusses the pros and cons of drug therapy for immune
      thrombocytopenic purpura in children.

PMID- 15511618
TI  - Thrombosis during infancy and childhood: what we know and what we do not know.
AB  - Despite underlying illnesses, children have a greater chance to survive and are
      expected to live 6 to 8 decades following an episode of venous or arterial
      thrombosis. The disproportionate benefits of preventing thrombosis and its
      sequelae in pediatric patients are evident. Therefore, it is necessary to develop
      appropriate strategies for diagnosis and management of thromboembolic events in
      children and to understand their acute and long-term effects. There still are
      many unanswered questions and clinical trials are being designed to help study
      these important issues.

PMID- 15511619
TI  - Risk factors and prediction of outcomes in children and adolescents who have
      sickle cell anemia.
AB  - This article discusses risk factors and prediction in children and adolescents
      who have sickle cell anemia.

PMID- 15511620
TI  - Iron chelation therapy in sickle-cell disease and other transfusion-dependent
      anemias.
AB  - Regular red cell transfusion therapy may be life-saving or may reduce
      complications substantially in several hematological disorders. The inevitable
      consequence of repeated transfusions is iron loading, which, if untreated, leads
      to organ failure and death. Chelation therapy with deferoxamine is the standard
      of care for patients who have transfusional iron overload. The necessity to
      administer this drug parenterally limits compliance; this has prompted the search
      for a safe and effective orally-administered chelator. Deferiprone, the first
      extensively studied orally active chelator, is now licensed for use in Europe for
      patients who are unable to use deferoxamine effectively or safely. ICL670, a
      newer oral chelator, is being tested in large clinical trials. Combined
      therapies, potentially including transfusional methods to reduce iron loading
      with parenteral and oral chelators, may improve compliance and efficacy in some
      patients who are transfused chronically.

PMID- 15511621
TI  - Iron homeostasis and inherited iron overload disorders: an overview.
AB  - Iron is an ubiquitous metal of vital importance to the normal physiologic
      processes of many organisms. Recent discoveries of mutations in genes that lead
      to inherited iron overload diseases have advanced the understanding of iron
      homeostasis in humans. This article provides an overview of the human iron cycle,
      regulation of iron homeostasis, how perturbations in this homeostasis lead to
      iron overload disease in adults and children, and strategies for diagnosis of
      inherited iron overload.

PMID- 15511622
TI  - Hematologic problems in immigrants from Southeast Asia.
AB  - An increasing number of Southeast Asian immigrants have come to North America.
      Physicians who care for this population should be aware of the high prevalence of
      hematologic disorders and develop an approach to their diagnosis and management.
      Malaria and the hematologic sequelae, glucose-6-phophate dehydrogenase
      deficiency, the thalassemia syndromes, Southeast Asian ovalocytosis, visceral
      leishmaniasis, HIV infection, and iron-deficiency anemia, all of which may
      pertain to these patients, are reviewed in this article.

PMID- 15511623
TI  - Trends in diagnosis and management of iron deficiency during infancy and early
      childhood.
AB  - Iron deficiency remains a public health challenge. The neurocognitive deficits
      that are associated with iron deficiency are most worrisome. Moreover, iron
      deficiency-associated elevated blood lead levels magnify the problem.
      Pediatricians must strive to prevent iron deficiency.

PMID- 15511624
TI  - Update on childhood neutropenia: molecular and clinical advances.
AB  - Congenital and inherited disorders are important differential diagnoses of
      neutropenia, particularly in neonates and children, although acquired causes are
      more common. This article focuses on recent advances in understanding the
      cellular and molecular defects in inherited neutropenias as well as issues that
      are related to clinical presentation, diagnosis, and complications.

PMID- 15511625
TI  - Identification and characterisation of a novel KCNQ1 mutation in a family with
      Romano-Ward syndrome.
AB  - Romano-Ward syndrome (RWS), the autosomal dominant form of the congenital long QT
      syndrome, is characterised by prolongation of the cardiac repolarisation process
      associated with ventricular tachyarrhythmias of the torsades de pointes type.
      Genetic studies have identified mutations in six ion channel genes, KCNQ1, KCNH2,
      SCN5A, KCNE1 and KCNE2 and the accessory protein Ankyrin-B gene, to be
      responsible for this disorder. Single-strand conformation polymorphism (SSCP)
      analysis and subsequent DNA sequence analysis have identified a KCNQ1 mutation in
      a family that were clinically conspicuous due to several syncopes and prolonged
      QTc intervals in the ECG. The mutant subunit was expressed and functionally
      characterised in the Xenopus oocyte expression system. A novel heterozygous
      missense mutation with a C to T transition at the first position of codon 343
      (CCA) of the KCNQ1 gene was identified in three concerned family members (QTc
      intervals: 500, 510 and 530 ms, respectively). As a result, proline 343 localised
      within the highly conserved transmembrane segment S6 of the KCNQ1 channel is
      replaced by a serine. Co-expression of mutant (KCNQ1-P343S) and wild-type (KCNQ1)
      cRNA in Xenopus oocytes produced potassium currents reduced by approximately 92%,
      while IKs reconstitution experiments with a combination of KCNQ1 mutant, wild
      type and KCNE1 subunits yielded currents reduced by approximately 60%. A novel
      mutation (P343S) identified in the KCNQ1 subunit gene of three members of a RWS
      family showed a dominant-negative effect on native IKs currents leading to
      prolongation of the heart repolarisation and possibly increases the risk of
      malign arrhythmias with sudden cardiac death.

PMID- 15511626
TI  - Anti-amyloidogenic activity of tannic acid and its activity to destabilize
      Alzheimer's beta-amyloid fibrils in vitro.
AB  - Inhibition of the accumulation of amyloid beta-peptide (Abeta) and the formation
      of beta-amyloid fibrils (fAbeta) from Abeta, as well as the destabilization of
      preformed fAbeta in the CNS would be attractive therapeutic targets for the
      treatment of Alzheimer's disease (AD). We previously reported that
      nordihydroguaiaretic acid (NDGA) and wine-related polyphenols inhibit fAbeta
      formation from Abeta(1-40) and Abeta(1-42) as well as destabilizing preformed
      fAbeta(1-40) and fAbeta(1-42) dose-dependently in vitro. Using fluorescence
      spectroscopic analysis with thioflavin T and electron microscopic studies, we
      examined the effects of polymeric polyphenol, tannic acid (TA) on the formation,
      extension, and destabilization of fAbeta(1-40) and fAbeta(1-42) at pH 7.5 at 37
      degrees C in vitro. We next compared the anti-amyloidogenic activities of TA with
      myricetin, rifampicin, tetracycline, and NDGA. TA dose-dependently inhibited
      fAbeta formation from Abeta(1-40) and Abeta(1-42), as well as their extension.
      Moreover, it dose-dependently destabilized preformed fAbetas. The effective
      concentrations (EC50) of TA for the formation, extension and destabilization of
      fAbetas were in the order of 0-0.1 microM. Although the mechanism by which TA
      inhibits fAbeta formation from Abeta as well as destabilizes preformed fAbeta in
      vitro is still unclear, it could be a key molecule for the development of
      therapeutics for AD.

PMID- 15511627
TI  - Significantly increased fractions of transformed to total alpha2-macroglobulin
      concentrations in plasma from patients with multiple sclerosis.
AB  - We examined the proteinase inhibitor alpha2-macroglobulin (alpha2M) in plasma
      from patients with multiple sclerosis (MS); a neurological disease of the central
      nervous system. The plasma concentrations of native and transformed alpha2M were
      measured in 90 patients with clinically definite MS, 73 with relapsing-remitting
      and 17 with secondary progressive MS, and 132 healthy individuals. Significantly
      lower concentrations of native alpha2M and significantly higher concentrations of
      transformed alpha2M were found in MS patients. A significant correlation between
      the concentrations of native and transformed alpha2M was found. The fraction of
      transformed to total alpha2M in the MS patients was 36% higher than in the
      healthy individuals. The results suggest an important involvement of alpha2M in
      regulation of increased proteolytic activity occurring in MS disease.

PMID- 15511628
TI  - Restoration of copper metabolism and rescue of hepatic abnormalities in LEC rats,
      an animal model of Wilson disease, by expression of human ATP7B gene.
AB  - Hepatic abnormalities in Long-Evans Cinnamon (LEC) rats, an animal model of
      Wilson disease (WD), were restored by the expression of the human ATP7B cDNA
      under the control of CAG promoter. Expression of ATP7B transcript and protein in
      the liver of the transgenic rats resulted in the restoration of biosynthesis of
      holoceruloplasmin and biliary copper excretion. Meanwhile, transgenic rats showed
      striking improvements in their hepatic abnormalities, i.e., rescue from fulminant
      hepatitis, late onset of hepatic cholangiofibrosis, suppression of hepatocellular
      carcinoma and much improved survival rates. Moreover, dramatic decreases were
      noted both in the levels of hepatic copper and iron in transgenic rats before the
      occurrence of hepatitis. These results indicated that the human ATP7B product
      compensated for the deficiency of the endogenous rattus protein and did function
      in intrahepatic copper transport by secreting copper into the plasma via
      incorporation into ceruloplasmin and by the excretion of copper into the bile,
      and that ATP7B is critical to hepatic dysfunctions in WD. This first successful
      transgenic rescue has important implications for the gene therapy of WD.

PMID- 15511629
TI  - Deamidation and cross-linking of gliadin peptides by transglutaminases and the
      relation to celiac disease.
AB  - Activation of small intestinal gluten-reactive CD4+ T cells is a critical event
      in celiac disease. Such cells predominantly recognise gluten peptides in which
      specific glutamines are deamidated. Deamidation may be catalysed by intestinal
      tissue transglutaminase (TG2), a protein which is also the main autoantigen in
      celiac disease. Our aim was to study how the two main catalytic activities of
      transglutaminase--deamidation and transamidation (cross-linking) of an
      immunodominant gliadin epitope--are influenced by the presence of acceptor amines
      in the intestinal mucosa, and thereby contribute to further elucidation of the
      pathogenetic mechanisms in celiac disease. We prepared monoclonal antibodies,
      reacting specifically with the non-deamidated epitope QPFPQPQLPYPQPQ-amide and/or
      the deamidated epitope QPFPQPELPYPQPQ-amide. A solid phase immunoassay combined
      with gel filtration chromatography was used to analyse deamidation and cross
      linking of these peptides to proteins. Our results show that QPFPQPQLPYPQPQ-amide
      was deamidated when incubated with purified TG2, with fresh mucosal sheets and
      with mucosal homogenates. Of other transglutaminases tested, only
      Streptoverticillium transglutaminase was able to generate the deamidated epitope.
      A fraction of the non-deamidated epitope was cross-linked to proteins, including
      TG2. The results suggest that intestinal TG2 is responsible for generation of the
      active deamidated epitope. As the epitope often occurs in a repeat structure, the
      result may be cross-linking of a deamidated, i.e., activated cell epitope.
      Alternatively, the deamidation may occur by reversal of the cross-linking
      reaction. The results provide a basis for the suggestion that binding of a
      peptide to a protein, in connection to its modification to a T cell epitope,
      might be a general explanation for the role of TG2 in celiac disease and a
      possible mechanism for the generation of autoantigens.

PMID- 15511630
TI  - Effects of chronic renal failure on caveolin-1, guanylate cyclase and AKT protein
      expression.
AB  - Chronic renal failure (CRF) has been documented to cause oxidative stress and
      alter nitric oxide (NO) metabolism. However, the effect of CRF on proteins
      related to NO bioactivity has not been investigated. The present study was
      designed to test the hypothesis that CRF would induce changes in caveolin-1 (Cav
      1), soluble guanylate cyclase (sGC) and Akt, three proteins important in
      regulating NO synthase (NOS) functionality. Male Sprague-Dawley rats were
      randomized to CRF via 5/6 nephrectomy or sham-operated control groups. After 6
      weeks, body weight, blood pressure, creatinine clearance, plasma creatinine,
      urinary cyclic guanosine monophosphate (cGMP) and immunodetectable levels of Cav
      1, sGC and Akt were determined in the renal, aorta, heart and liver tissues from
      both groups. CRF resulted in marked decreases in body weight and creatinine
      clearance, and elevation of blood pressure and plasma creatinine. An apparent
      upregulation of sGC protein abundance in renal tissue was noted, with no change
      in aorta, heart and liver. This was accompanied by a reduction in urinary cGMP
      levels, indicative of sGC dysfunction. Cav-1 protein abundance was increased in
      aortic, liver and renal tissues. In contrast, CRF depressed Akt abundance in
      aorta, heart and liver tissues. These data document that CRF is characterized by
      alteration in the abundance of proteins regulating NO function in hepatic,
      vascular, cardiac and renal tissues, and a decrease in cGMP, which contributes to
      hypertension and changes in NO bioactivity previously noted in this model.

PMID- 15511631
TI  - A high proportion of polymorphisms in the promoters of brain expressed genes
      influences transcriptional activity.
AB  - There is increasing interest in the possibility that polymorphisms affecting gene
      expression are responsible for a significant proportion of heritable human
      phenotypic variation, including human disease. We have sought to determine if
      polymorphisms in the promoters of brain expressed genes are commonly functional.
      We screened for polymorphism 56 genes previously reported to be differentially
      expressed in the brains of schizophrenics [Y. Hakak, J.R. Walker, C. Li, W.H.
      Wong, K.L. Davis, J.D. Buxbaum, V. Haroutunian, A.A. Fienberg, Genome-wide
      expression analysis reveals dysregulation of myelination-related genes in chronic
      schizophrenia. Proc. Natl. Acad. Sci. 98 (2001) 4746-4751.]. We found 60 variants
      distributed across 31 of the genes. A total of 77 haplotypes representing 28
      different putative promoters were analyzed in a reporter gene assay in two cell
      lines. Of a total of 54 sequence variants represented in the haplotypes, 12 (or
      around 22%) were functional according to a highly conservative definition. These
      were found in the promoters of eight genes: NPY, PCSK1, NEFL, KIAA0513, LMO4,
      HSPA1B, TF and MDH1. We therefore estimate that around 20-25% of promoter
      polymorphisms in brain expressed genes are functional, and this is likely to be
      an underestimate. Our data therefore provide for the first time empirical
      evidence that promoter element polymorphisms, at least in brain expressed genes,
      should be afforded a high priority for molecular genetic studies.

PMID- 15511632
TI  - Transgenic mouse expressing human mutant alpha-galactosidase A in an endogenous
      enzyme deficient background: a biochemical animal model for studying active-site
      specific chaperone therapy for Fabry disease.
AB  - Fabry disease is an inborn error of glycosphingolipid metabolism caused by the
      deficiency of lysosomal alpha-galactosidase A (alpha-Gal A). We have established
      transgenic mice that exclusively express human mutant alpha-Gal A (R301Q) in an
      alpha-Gal A knock-out background (TgM/KO mice). This serves as a biochemical
      model to study and evaluate active-site specific chaperone (ASSC) therapy for
      Fabry disease, which is specific for those missense mutations that cause
      misfolding of alpha-Gal A. The alpha-Gal A activities in the heart, kidney,
      spleen, and liver of homozygous TgM/KO mice were 52.6, 9.9, 29.6 and 44.4 unit/mg
      protein, respectively, corresponding to 16.4-, 0.8-, 0.6- and 1.4-fold of the
      endogenous enzyme activities in the same tissues of non-transgenic mice with a
      similar genetic background. Oral administration of 1-deoxygalactonojirimycin
      (DGJ), a competitive inhibitor of alpha-Gal A and an effective ASSC for Fabry
      disease, at 0.05 mM in the drinking water of the mice for 2 weeks resulted in
      13.8-, 3.3-, 3.9-, and 2.6-fold increases in enzyme activities in the heart,
      kidney, spleen and liver, respectively. No accumulation of globotriaosylceramide,
      a natural substrate of alpha-Gal A, could be detected in the heart of TgM/KO mice
      after DGJ treatment, indicating that degradation of the glycolipid in the heart
      was not inhibited by DGJ at that dosage. The alpha-Gal A activity in homozygous
      or heterozygous fibroblasts established from TgM/KO mice (TMK cells) was
      approximately 39 and 20 unit/mg protein, respectively. These TgM/KO mice and TMK
      cells are useful tools for studying the mechanism of ASSC therapy, and for
      screening ASSCs for Fabry disease.

PMID- 15511633
TI  - The oxidants hypochlorite and hydrogen peroxide induce distinct patterns of acute
      lung injury.
AB  - Oxidative stress due to activated neutrophils, macrophages and endothelial cells
      plays a crucial role in acute lung injury. This study compares the effects of the
      nonradical oxidants hypochlorite (HOCl) and hydrogen peroxide (H2O2) on pulmonary
      artery pressure [PAPtorr], capillary filtration coefficient (Kf,c), tissue lipid
      peroxidation (LPO) and reduced glutathione (GSH) depletion. HOCl, H2O2 (1000 nmol
      min(-1)) or buffer (control) is infused into isolated rabbit lungs. PAP, K(f,c)
      and lung weight were measured. Experiments were terminated after 105 min or when
      fluid retention exceeded 50 g. Lung tissue was analyzed for LPO products and GSH.
      The oxidants induced comparable maximum effects. However, the patterns of lung
      injury were distinct: H2O2 infusion evoked an early biphasic pressure response
      (DeltaPAPmax 2.8+/-0.22/4.2+/-0.37 after 5.7+/-1.4/39+/-4.0 min) and a sixfold
      increase in Kf,c after 90 min. HOCl application caused a late pressure response
      (DeltaPAPmax 7.6+/-1.7 after 50.6+/-3.7 min) and a sevenfold increase in Kf,c
      after 60 min. H2O2-induced effects were attenuated by desferal. This may suggest
      an involvement of transition metal catalysed hydroxyl radical formation.
      Different oxidants induced distinct patterns of changes in PAP and Kf,c , which
      are accompanied by a comparable accumulation of LPO products and by a distinct
      degree of GSH depletion.

PMID- 15511634
TI  - Effects of adrenomedullin on aldosterone-induced cell proliferation in rat
      cardiac fibroblasts.
AB  - Aldosterone induces cardiac remodeling in cardiovascular diseases by stimulating
      the proliferation, production and secretion of collagen in fibroblasts. It also
      stimulates vascular smooth muscle cells to produce and secrete adrenomedullin
      (ADM), which has a cytoprotective effect against cardiovascular damage. We
      examined the effect of aldosterone on ADM production and secretion in rat cardiac
      fibroblasts, and the effect of ADM on aldosterone-stimulated fibroblast
      proliferation to observe the interaction between endogenous ADM and aldosterone.
      We detected ADM produced and secreted from cultured cardiac fibroblasts and the
      intracellular cAMP level by radioimmunoassay; evaluated cell proliferation by the
      level of [3H]-thymine incorporation; measured preproADM gene expression by
      reverse transcriptase polymerase chain reaction (RT-PCR); and monitored
      extracellular signal related kinase (ERK) activity by the phosphorylation of
      myelin basic protein in the presence of [gamma-32P] ATP. Our results showed that
      aldosterone-stimulated secretion of ADM and its mRNA expression were
      concentration-dependent, which could be inhibited by the specific antagonist of
      mineralocorticoid receptor, spironolactone. In contrast, ADM inhibited
      aldosterone-induced fibroblast proliferation and ERK activity. Treatment with
      ADM24-50 (a new antagonist of specific ADM receptors) and calcitonin gene-related
      peptide (CGRP)8-37 (the antagonist of CGRP receptor type 1), to attenuate the
      action of endogenous ADM, reinforced the aldosterone-induced proliferation and
      inhibited the intracellular cAMP production stimulated by aldosterone. Thiorphan,
      an inhibitor of ADM degradation, inhibited the [3H]-thymine incorporation and
      reinforced the intracellular cAMP level induced by aldosterone. We reach the
      conclusion that aldosterone stimulates rat cardiac fibroblasts to produce and
      secrete ADM, which in turn regulates the proliferation-induced effects of
      aldosterone in these cells.

PMID- 15511635
TI  - Methylthioadenosine phosphorylase gene expression is impaired in human liver
      cirrhosis and hepatocarcinoma.
AB  - Methylthioadenosine phosphorylase (MTAP) is a key enzyme in the methionine and
      adenine salvage pathways. In mammals, the liver plays a central role in
      methionine metabolism, and this essential function is lost in the progression
      from liver cirrhosis to hepatocarcinoma. Deficient MTAP gene expression has been
      recognized in many transformed cell lines and tissues. In the present work, we
      have studied the expression of MTAP in human and experimental liver cirrhosis and
      hepatocarcinoma. We observe that MTAP gene expression is significantly reduced in
      human hepatocarcinoma tissues and cell lines. Interestingly, MTAP gene expression
      was also impaired in the liver of CCl4-cirrhotic rats and cirrhotic patients. We
      provide evidence indicating that epigenetic mechanisms, involving DNA methylation
      and histone deacetylation, may play a role in the silencing of MTAP gene
      expression in hepatocarcinoma. Given the recently proposed tumor suppressor
      activity of MTAP, our observations can be relevant to the elucidation of the
      molecular mechanisms of multistep hepatocarcinogenesis.

PMID- 15511636
TI  - The homeodomain-containing transcription factor X-nkx-5.1 inhibits expression of
      the homeobox gene Xanf-1 during the Xenopus laevis forebrain development.
AB  - Expression of the homeobox gene Xanf-1 starts within the presumptive forebrain
      primordium of the Xenopus embryo at the midgastrula stage and is inhibited by the
      late neurula. Such stage-specific inhibition is essential for the normal
      development as the experimental prolongation of the Xanf-1 expression elicits
      severe brain abnormalities. To identify transcriptional regulators that are
      responsible for the Xanf-1 inhibition, we have used the yeast one-hybrid system
      and identified a novel Xenopus homeobox gene X-nkx-5.1 that belongs to a family
      of Nkx-5.1 transcription factors. In terms of gene expression, X-nkx-5.1 shares
      many common features with its orthologs in other species, including expression in
      the embryonic brain and in the ciliated cells of the otic and lateral line
      placodes. However, we have also observed several features specific for X-nkx-5.1,
      such as expression in precursors of the epidermal ciliated cells that may
      indicate a possible common evolutionary origin of all ciliated cells derived from
      the embryonic ectoderm. Another specific feature is that the X-nkx-5.1 expression
      in the anterior neural plate starts early, within the area overlapping the Xanf-1
      expression territory at the midneurula stage, and it correlates with the
      beginning of the Xanf-1 inhibition. Using various loss and gain-of-function
      techniques, including microinjections of antisense morpholino oligonucleotides
      and mRNA encoding for the X-nkx-5.1 and its dominant repressor and activator
      versions, we have shown that X-nkx-5.1 can indeed play a role of stage-specific
      inhibitor of Xanf-1 in the anterior neural plate during the Xenopus development.

PMID- 15511637
TI  - Mouse Nkd1, a Wnt antagonist, exhibits oscillatory gene expression in the PSM
      under the control of Notch signaling.
AB  - During vertebrate embryogenesis, the formation of reiterated structures along the
      body axis is dependent upon the generation of the somite by segmentation of the
      presomitic mesoderm (PSM). Notch signaling plays a crucial role in both the
      generation and regulation of the molecular clock that provides the spatial
      information for PSM cells to form somites. In a screen for novel genes involved
      in somitogenesis, we identified a gene encoding a Wnt antagonist, Nkd1, which is
      transcribed in an oscillatory manner, and may represent a new member of the
      molecular clock constituents. The transcription of nkd1 is extremely
      downregulated in the PSM of vestigial tail (vt/vt), a hypomorphic mutant of
      Wnt3a, whereas nkd1 oscillations have a similar phase to lunatic fringe (L-fng)
      transcription and they are arrested in Hes7 (a negative regulator of Notch
      signaling) deficient embryos. These results suggest that the transcription of
      nkd1 requires Wnt3a, and that its oscillation patterns depend upon the function
      of Hes7. Wnt signaling has been postulated to be upstream of Notch signaling but
      we demonstrate in this study that a Wnt-signal-related gene may also be regulated
      by Notch signaling. Collectively, our data suggest that the reciprocal
      interaction of Notch and Wnt signals, and of their respective negative feedback
      loops, function to organize the segmentation clock required for somitogenesis.

PMID- 15511638
TI  - SNS: Adhesive properties, localization requirements and ectodomain dependence in
      S2 cells and embryonic myoblasts.
AB  - The body wall muscles in the Drosophila larva arise from interactions between
      Duf/Kirre and Irregular chiasm C-roughest (IrreC-rst)-expressing founder
      myoblasts and sticks-and-stones (SNS)-expressing fusion competent myoblasts in
      the embryo. Herein, we demonstrate that SNS mediates heterotypic adhesion of S2
      cells with Duf/Kirre and IrreC-rst-expressing S2 cells, and colocalizes with
      these proteins at points of cell contact. These properties are independent of
      their transmembrane and cytoplasmic domains, and are observed quite readily with
      GPI-anchored forms of the ectodomains. Heterotypic interactions between Duf/Kirre
      and SNS-expressing S2 cells occur more rapidly and to a greater extent than
      homotypic interactions with other Duf/Kirre-expressing cells. In addition,
      Duf/Kirre and SNS are present in an immunoprecipitable complex from S2 cells. In
      the embryo, Duf/Kirre and SNS are present at points of contact between founder
      and fusion competent cells. Moreover, SNS clustering on the cell surface is
      dependent on Duf/Kirre and/or IrreC-rst. Finally, although the cytoplasmic and
      transmembrane domains of SNS are expendable for interactions in culture, they are
      essential for fusion of embryonic myoblasts.

PMID- 15511639
TI  - MAE, a dual regulator of the EGFR signaling pathway, is a target of the Ets
      transcription factors PNT and YAN.
AB  - Ets transcription factors play crucial roles in regulating diverse cellular
      processes including cell proliferation, differentiation and survival. Coordinated
      regulation of the Drosophila Ets transcription factors YAN and POINTED is
      required for eliciting appropriate responses to Receptor Tyrosine Kinase (RTK)
      signaling. YAN, a transcriptional repressor, and POINTED, a transcriptional
      activator, compete for regulatory regions of common target genes, with the
      ultimate outcome likely influenced by context-specific interactions with binding
      partners such as MAE. Previous work in cultured cells has led us to propose that
      MAE attenuates the transcriptional activity of both YAN and POINTED, although its
      effects on POINTED remain controversial. Here we describe a new layer of
      complexity to this regulatory hierarchy whereby mae expression is itself directly
      regulated by the opposing action of YAN and POINTED. In addition, we report that
      MAE can antagonize POINTED function during eye development; a finding that
      suggests MAE operates as a dual positive and negative regulator of RTK-mediated
      signaling in vivo. Together our results lead us to propose that a combination of
      protein-protein and transcriptional interactions between MAE, YAN and POINTED
      establishes a complex regulatory circuit that ensures that both down-regulation
      and activation of the RTK pathway occur appropriately according to specific
      developmental context.

PMID- 15511640
TI  - RLIP mediates downstream signalling from RalB to the actin cytoskeleton during
      Xenopus early development.
AB  - The Ras protein activates at least three different pathways during early
      development. Two of them regulate mesodermal gene expression and the third is
      thought to participate in the control of actin cytoskeleton dynamics via the Ral
      protein. From a yeast two-hybrid screen of a Xenopus maternal cDNA library, we
      identified the Xenopus orthologue of the Ral interacting protein (RLIP, RIP1 or
      RalBP1), a putative effector of small G protein Ral. Previously, we observed that
      a constitutively activated form of Ral GTPase (XralB G23V) induced bleaching of
      the animal hemisphere and disruption of the cortical actin cytoskeleton. To
      demonstrate that RLIP is the effector of RalB in early development, we show that
      the artificial targeting of RLIP to the membrane induces a similar phenotype to
      that of activated RalB. We show that overexpression of the Ral binding domain
      (RalBD) of XRLIP, which binds to the effector site of Ral, acts in competition
      with the endogenous effector of Ral and protects against the destructive effect
      of XralB G23V on the actin cytoskeleton. In contrast, the XRLIP has a synergistic
      effect on the activated form of XralB, which is dependent on the RalBD of RLIP.
      We provide evidence for the involvement of RLIP by way of its RalBD on the
      dynamics of the actin cytoskeleton and propose that signalling from Ral to RLIP
      is required for gastrulation.

PMID- 15511641
TI  - Cullin-3 regulates pattern formation, external sensory organ development and cell
      survival during Drosophila development.
AB  - Ubiquitin-mediated proteolysis regulates the steady-state abundance of proteins
      and controls cellular homoeostasis by abrupt elimination of key effector
      proteins. A multienzyme system targets proteins for destruction through the
      covalent attachment of a multiubiquitin chain. The specificity and timing of
      protein ubiquitination is controlled by ubiquitin ligases, such as the Skp1
      Cullin-F box protein complex. Cullins are major components of SCF complexes, and
      have been implicated in degradation of key regulatory molecules including Cyclin
      E, beta-catenin and Cubitus interruptus. Here, we describe the genetic
      identification and molecular characterisation of the Drosophila Cullin-3
      homologue. Perturbation of Cullin-3 function has pleiotropic effects during
      development, including defects in external sensory organ development, pattern
      formation and cell growth and survival. Loss or overexpression of Cullin-3 causes
      an increase or decrease, respectively, in external sensory organ formation,
      implicating Cullin-3 function in regulating the commitment of cells to the neural
      fate. We also find that Cullin-3 function modulates Hedgehog signalling by
      regulating the stability of full-length Cubitus interruptus (Ci155). Loss of
      Cullin-3 function in eye discs but not other imaginal discs promotes cell
      autonomous accumulation of Ci155. Conversely, overexpression of Cullin-3 results
      in a cell-autonomous stabilisation of Ci155 in wing, haltere and leg, but not
      eye, imaginal discs suggesting tissue-specific regulation of Cullin-3 function.
      The diverse nature of Cullin-3 phenotypes highlights the importance of targeted
      proteolysis during Drosophila development.

PMID- 15511642
TI  - A role for nucleoprotein Zap3 in the reduction of telomerase activity during
      embryonic stem cell differentiation.
AB  - Telomerase, the enzyme which maintains the ends of linear chromosomes in
      eukaryotic cells is found in murine embryonic stem cells; however, its activity
      is downregulated during in vitro differentiation. Previous work has indicated
      that this is due to the transcriptional downregulation of murine reverse
      transcriptase unit (mTert) of telomerase. To investigate the factors that cause
      the transcriptional repression of mTert we defined a 300 bp region which is
      essential for its transcription and performed site directed mutagenesis and
      electrophoretic mobility shift assays. This analysis indicated that Sp1, Sp3 and
      c-Myc bind to the GC-boxes and E-boxes, respectively, within the promoter and
      help activate the transcription of mTert gene. We also identified a novel binding
      sequence, found repeated within the mTert core region, which when mutated caused
      increased mTert expression. Yeast one hybrid screening combined with
      electrophoretic mobility shift assays indicated that the nuclear protein Zap3
      binds to this site and its overexpression leads to the downregulation of mTert
      during differentiation. This suggests that regulation of mTert transcription is a
      complex process which depends on a quantitative balance between transcription
      factors that cause activation or repression of this gene. Overexpression of Zap3
      in murine embryonic stem cells results in reduction in telomerase activity and
      telomere length as well as reduced proliferative capacity and limited ability to
      contribute to the development of haematopoietic cells upon differentiation.

PMID- 15511643
TI  - A role for wingless in an early pupal cell death event that contributes to
      patterning the Drosophila eye.
AB  - Programmed cell death (PCD) is utilized in a wide variety of tissues to refine
      structure in developing tissues and organs. However, little is understood about
      the mechanisms that, within a developing epithelium, combine signals to
      selectively remove some cells while sparing essential neighbors. One popular
      system for studying this question is the developing Drosophila pupal retina,
      where excess interommatidial support cells are removed to refine the patterned
      ommatidial array. In this paper, we present data indicating that PCD occurs
      earlier within the pupal retina than previously demonstrated. As with later PCD,
      this death is dependent on Notch activity. Surprisingly, altering Drosophila
      Epidermal Growth Factor Receptor or Ras pathway activity had no effect on this
      death. Instead, our evidence indicates a role for Wingless signaling to provoke
      this cell death. Together, these signals regulate an intermediate step in the
      selective removal of unneeded interommatidial cells that is necessary for a
      precise retinal pattern.

PMID- 15511644
TI  - The jing and ras1 pathways are functionally related during CNS midline and
      tracheal development.
AB  - The Drosophila jing gene encodes a zinc finger protein required for the
      differentiation and survival of embryonic CNS midline and tracheal cells. We show
      that there is a functional relationship between jing and the Egfr pathway in the
      developing CNS midline and trachea. jing function is required for Egfr pathway
      gene expression and MAPK activity in both the CNS midline and trachea. jing over
      expression effects phenocopy those of the Egfr pathway and require Egfr pathway
      function. Activation of the Egfr pathway in loss-of-function jing mutants
      partially rescues midline cell loss. Egfr pathway genes and jing show dominant
      genetic interactions in the trachea and CNS midline. Together, these results show
      that jing regulates signal transduction in developing midline and tracheal cells.

PMID- 15511645
TI  - Interaction between the nature of the information and the cognitive requirement
      of the task in problem solving in mice.
AB  - The Morris water maze and the radial-arm maze are two of the most frequently
      employed behavioral tasks used to assess spatial memory in rodents. In this
      study, we describe two new behavioral tasks in a radial-arm water maze enabling
      to combine the advantages of the Morris water maze and the radial-arm maze. In
      both tasks, spatial and nonspatial learning was assessed and the only task
      parameter that varied was the nature of the information available which was
      either spatial (various distal extra-maze cues) or nonspatial (visual intra-maze
      patterns). In experiment 1, 129T2/Sv mice were able to learn three successive
      pairwise discriminations [(1) A+/B-, (2) B+/C-, (3) C+/A-] with the same
      efficiency in both modalities (i.e. spatial and nonspatial modalities). Probe
      trials at the end of each of these discriminations revealed particular features
      of this transverse-patterning-like procedure. In experiment 2, another group of
      129T2/Sv mice was submitted to a delayed matching-to-sample working memory task.
      Mice were able to learn the task and were then able to show resistance to
      temporal interference as long as 60 min in the spatial modality but they failed
      to acquire the task in the nonspatial modality. The fact that the nonspatial
      information was exactly the same in both experiments highlights the existence of
      an interaction between the cognitive requirements of the task and the nature of
      the information.

PMID- 15511646
TI  - Factors influencing audiovisual fission and fusion illusions.
AB  - Information processing in auditory and visual modalities interacts in many
      circumstances. Spatially and temporally coincident acoustic and visual
      information are often bound together to form multisensory percepts [B.E. Stein,
      M.A. Meredith, The Merging of the Senses, A Bradford Book, Cambridge, MA, (1993),
      211 pp.; Psychol. Bull. 88 (1980) 638]. Shams et al. recently reported a
      multisensory fission illusion where a single flash is perceived as two flashes
      when two rapid tone beeps are presented concurrently [Nature 408 (2000) 788;
      Cogn. Brain Res. 14 (2002) 147]. The absence of a fusion illusion, where two
      flashes would fuse to one when accompanied by one beep, indicated a perceptual
      rather than cognitive nature of the illusion. Here we report both fusion and
      fission illusions using stimuli very similar to those used by Shams et al. By
      instructing subjects to count beeps rather than flashes and decreasing the sound
      intensity to near threshold, we also created a corresponding visually induced
      auditory illusion. We discuss our results in light of four hypotheses of
      multisensory integration, each advocating a condition for modality dominance.
      According to the discontinuity hypothesis [Cogn. Brain Res. 14 (2002) 147], the
      modality in which stimulation is discontinuous dominates. The modality
      appropriateness hypothesis [Psychol. Bull. 88 (1980) 638] states that the
      modality more appropriate for the task at hand dominates. The information
      reliability hypothesis [J.-L. Schwartz, J. Robert-Ribes, P. Escudier, Ten years
      after Summerfield: a taxonomy of models for audio-visual fusion in speech
      perception. In: R. Campbell (Ed.), Hearing by Eye: The Psychology of Lipreading,
      Lawrence Earlbaum Associates, Hove, UK, (1998), pp. 3-51] claims that the
      modality providing more reliable information dominates. In strong forms, none of
      these three hypotheses applies to our data. We re-state the hypotheses in weak
      forms so that discontinuity, modality appropriateness and information reliability
      are factors which increase a modality's tendency to dominate. All these factors
      are important in explaining our data. Finally, we interpret the effect of
      instructions in light of the directed attention hypothesis which states that the
      attended modality is dominant [Psychol. Bull. 88 (1980) 638].

PMID- 15511647
TI  - The cortical representation of foveal stimuli: evidence from quadrantanopia and
      TMS-induced suppression.
AB  - To address the extent to which the visual foveal representation is split, we
      examined a 29-year-old patient with a lower right quadrantanopia following
      surgical removal of the left occipital cortex above the calcarine sulcus and
      compared her performance with subjects receiving transcranial magnetic
      stimulation (TMS) over the occipital lobes. In a letter/digit classification
      task, the patient responded accurately to targets presented in the upper visual
      field, for all horizontal eccentricities. In the lower visual field, she failed
      to discriminate letters from digits when targets were presented in the right, but
      not the left visual field (RVF and LVF, respectively). This pattern was also true
      for the foveal targets, with poor performance to foveal-RVF (0.5 degrees to the
      right of fixation) but not foveal-LVF (0.5 degrees to the left of fixation)
      targets. Similar patterns of normal performance to LVF but not RVF or foveal-RVF
      targets were observed in a group of nine normal observers when TMS was applied
      over their left occipital cortex. Complementary impairments to LVF and foveal-LVF
      target classification were induced with TMS over the right occipital cortex.
      Thus, we have induced an hemianopic pattern in normal observers contralateral to
      the magnetically stimulated hemisphere. This correspondence between real and TMS
      induced visual field defects is further evidence, in neurologically intact
      subjects, that the cortical representation of the fovea is split between the two
      hemispheres along the vertical meridian.

PMID- 15511649
TI  - Sound lateralization in Parkinson's disease.
AB  - The symptoms primarily associated with Parkinson's disease (PD) are of a motor
      and cognitive nature, but sensory deficits may also be involved. Previous studies
      have reported disturbed spatial perception in visual and tactile tasks. We have
      investigated whether PD patients show deficits in auditory spatial perception.
      For this purpose, we employed a simple task involving left/right judgments about
      dichotic stimuli presented with various interaural time differences (ITD). The
      acuity of sound lateralization was significantly reduced in PD: the just
      noticeable difference (JND) in interaural time seen in PD patients was about
      twice that seen for age-matched healthy controls. We propose that this deficit
      may be related to a potential role of the basal ganglia in spatial hearing
      functions, as has been suggested by neurophysiological and neuroanatomical
      studies on animals.

PMID- 15511648
TI  - Texture segmentation and visual search for pop-out targets. An ERP study.
AB  - "Parallel" visual search and effortless texture segmentation were believed to
      rely on similar mechanisms until Wolfe [Vis. Res. 32 (1992) 757] demonstrated
      that efficient visual search and effortless texture segmentation are not always
      the same thing. In a recent study, Meinecke and Donk [Perception 31 (2002) 591]
      varied display size in a pop-out task and found that, albeit stimulus elements
      and the task remained the same, different set sizes led to different processing
      modes. These findings indicate that it may suffice to vary set size in an
      otherwise unchanged pop-out task to initiate different processing which may be
      similar to the processing in efficient visual search and in effortless texture
      segmentation. In four experiments, we further investigated this issue by
      presenting stimulus arrays of different set sizes while recording event-related
      brain potentials (ERPs). We found that when display size was increased, detection
      performance first decreased slightly before it then increased. ERP effects were
      observed for the posterior N2 (N2p), the N2pc and the P3 component. All three
      components showed variations with set size; N2p differential amplitude effects
      were confined to large set sizes, whereas an N2pc was obtained for a broader set
      size range except for very small set sizes and the largest set size (121
      elements). We interpret both the non-monotonic relationship between set size and
      response data and the variations of ERP components with set size as evidence in
      favor of different processing occurring for stimulus arrays with small and large
      set sizes.

PMID- 15511650
TI  - Orderly cortical representation of vowel categories presented by multiple
      exemplars.
AB  - This study aimed at determining how the human brain automatically processes
      phoneme categories irrespective of the large acoustic inter-speaker variability.
      Subjects were presented with 450 different speech stimuli, equally distributed
      across the [a], [i], and [u] vowel categories, and each uttered by a different
      male speaker. A 306-channel magnetoencephalogram (MEG) was used to record N1m,
      the magnetic counterpart of the N1 component of the auditory event-related
      potential (ERP). The N1m amplitude and source locations differed between vowel
      categories. We also found that the spectrum dissimilarities were reproduced in
      the cortical representations of the large set of the phonemes used in this study:
      vowels with similar spectral envelopes had closer cortical representations than
      those whose spectral differences were the largest. Our data further extend the
      notion of differential cortical representations in response to vowel categories,
      previously demonstrated by using only one or a few tokens representing each
      category.

PMID- 15511651
TI  - Changes in emotional tone and instrumental timbre are reflected by the mismatch
      negativity.
AB  - The present study examined whether or not the brain is capable to preattentively
      discriminate tones differing in emotional expression or instrumental timbre. In
      two event-related potential (ERP) experiments single tones (600 ms) were
      presented which had been rated as happy or sad in a pretest. In experiment 1, 12
      non-musicians passively listened to tone series comprising a frequent (standard)
      single musical tone played by a violin in a certain pitch and with a certain
      emotional connotation (happy or sad). Among these standard tones deviant tones
      differing in emotional valence, either in instrumental timbre or in pitch were
      presented. All deviants generated mismatch negativity (MMN) responses. The MMN
      scalp topography was similar for all of the three deviants but latency was
      shorter for pitch deviants than for the other two conditions. The topography of
      the mismatch responses was indistinguishable. In a second experiment, subjects
      actively detected the deviant tones by button press. All detected deviants
      generated P3b waves at parietal leads. These results indicate that the brain is
      not only able to use simple physical differences such as pitch for rapid
      preattentive categorization but can also perform similar operations on the basis
      of more complex differences between tones of the same pitch such as instrumental
      timbre and the subtle timbral differences associated with different emotional
      expression. This rapid categorization may serve as a basis for the further fine
      grained analysis of musical (and other) sounds with regard to their emotional
      content.

PMID- 15511652
TI  - Developmental dyslexia: ERP correlates of anomalous phonological processing
      during spoken word recognition.
AB  - Ample evidence suggests that developmental dyslexia results from a phonological
      deficit that may not be reducible to a low-level auditory deficit. Yet, on-line
      phonological processing (in)capacities in dyslexics remain virtually unexplored,
      as studies have typically focused on either meta-phonological awareness tasks or,
      at the other extreme, basic perceptual tasks. The present study investigates
      event-related potential (ERP) correlates of implicit phonological processing
      during the recognition of spoken words in dyslexic and normally reading children
      (7-10 years). We examined general ERP morphology and alliteration priming effects
      on ERP measures in an auditory lexical decision task. Primes were words
      (Experiment 1) and non-words (Experiment 2). Alliteration priming effects
      suggested a distinct pattern of normal versus anomalous aspects of spoken word
      processing in dyslexic children. Whereas dyslexics showed deviant priming effects
      in earlier time windows encompassing the N1 and N2, later N400 priming effects
      were comparable to those of normal readers. The same pattern of results was also
      present in group comparisons of general ERP morphology. These findings suggest
      that dyslexics have selective processing anomalies at an earlier
      phonetic/phonological level, while processing at a later phonological/lexical
      level proceeds normally. In particular, our results indicate an anomalous
      contribution of phonological (word onset) information to the processing of spoken
      words, which may be related to time-course aspects of phonetic/phonological
      processing.

PMID- 15511653
TI  - The influence of working memory load on phase specific patterns of cortical
      activity.
AB  - This study investigated patterns of cortical activity associated with the
      temporally separated encoding, maintenance and retrieval phases of a working
      memory (WM) task. Eighteen healthy subjects completed a variable load version of
      the Sternberg Item Recognition Task. Brain regions showing activity on average
      across load were determined for each task phase. In addition, brain regions
      showing activity that increased linearly with load were determined for encoding
      and retrieval. Although previous fMRI studies have used event-related designs to
      isolate phase specific activity, this study differed in that design and analysis
      methods were optimized to ensure low multicollinearity between the conditions of
      interest: the duration of the intermediate phase (maintenance) was varied and
      load was selectively modeled for the encoding and retrieval phases. The brain
      areas showing activity on average across load for each phase combine to encompass
      regions identified in previous studies that have not attempted to separate phase
      specific activity. Encoding is associated with extensive load dependent activity,
      with the most robust activity in bilateral occipital and posterior parietal
      regions. Retrieval is associated with more selective load dependent activity,
      primarily in the anterior supplementary motor region and the right posterior
      cerebellum. The analysis strategies employed in this study could be used to
      further delineate the phases of WM that are most severely compromised in clinical
      populations with WM disturbances.

PMID- 15511654
TI  - Face repetition effects in direct and indirect tasks: an event-related brain
      potentials study.
AB  - We investigated immediate repetition effects on event-related potentials (ERPs)
      during direct and indirect tasks for sequentially presented face pairs. The first
      face (F1) was presented masked or unmasked, and at different stimulus onset
      asynchronies (SOAs, 67 vs. 1000 ms) preceding the second face (F2). Experiment I
      (indirect task) required a semantic classification of F2, with F1 identity being
      irrelevant. Experiment II (direct task) used the same stimulus sequence but
      required a physical identity matching of F1 and F2. Whereas no masked repetition
      effects in behaviour or ERPs were seen, such effects were clearly shown for
      unmasked F1 faces. For short SOAs, an early-onset ( approximately 100 ms)
      occipital repetition effect, an inferior temporal N250r (200-300 ms) and a
      central-parietal N400 modulation (300-500 ms) were seen in both tasks, whereas a
      parietal P600 effect (500-800 ms) was only present in the indirect task. For long
      SOAs, the early occipital effect disappeared, suggesting that it reflects a fast
      decaying iconic memory trace. Clear task differences were seen for N250r, N400,
      and P600 modulations: P600 was larger for the indirect task, and may be a
      correlate of semantic analysis required by this task. By contrast, N250r and N400
      were larger for the direct task, suggesting that these components are sensitive
      to task relevance and/or attentional focus to F1, and thus do not reflect purely
      automatic facilitation in processing. This suggests an influence of strategic
      processing on the activation of both perceptual representations of faces and
      semantic representations of people.

PMID- 15511655
TI  - Neural foundations of emerging route knowledge in complex spatial environments.
AB  - Behavioral evidence suggests that spatial knowledge derived from ground-level
      navigation can consist of both route and survey knowledge. Neuroimaging and
      lesion studies aiming to identify the neural structures responsible for
      topographical learning in humans have yielded partially inconsistent results,
      probably due to the lack of an effective behavioral parameter allowing for a
      reliable distinction between different representations. Therefore, we employed a
      novel virtual reality environment that provides accuracy and reaction time
      measures precisely indicating the emergence of route vs. survey knowledge.
      Functional magnetic resonance imaging (fMRI) was used to localize brain regions
      involved in the acquisition of pure route knowledge in the form of associations
      between consecutive landmark views and the direction of intermediate movements.
      Participants were scanned during repeated encoding of the complex environment
      from a first-person, ground-level perspective. Behavioral data revealed emerging
      route knowledge in 11 out of 14 subjects. Overall comparisons between encoding
      and control conditions identified activation in medial frontal gyrus,
      retrosplenial cortex and posterior inferior parietal cortex. Most importantly,
      only posterior inferior parietal regions showed increasing activation across
      sessions, thus paralleling behavioral measures of route expertise. Given the
      established role of the posterior parietal cortex in spatial processing, this
      area is thought to provide the pivotal spatial link between two landmarks
      encountered in immediate temporal succession.

PMID- 15511656
TI  - Digit representation is more than just hand waving.
AB  - Lip-reading and interpreting hand gestures help provide nonverbal information
      that aids speech comprehension in noisy environments and places emphasis on
      certain key utterances. In this fMRI study, we examined if viewing the similar
      semantic information presented by either finger movements or lip movements was
      processed by common or discrete brain regions. Subjects viewed videos of a hand
      conveying number information via finger movements and a face whose lip movements
      conveyed the same numerical information. Control stimuli consisted of meaningless
      finger and lip movements. Lip-reading numbers activated left posterior superior
      temporal sulcus (STS), while identifying numbers presented by fingers activated
      the intraparietal region (IPR) bilaterally. Conjunction analysis highlighted
      common activation in right IPR to numbers presented via fingers and lips. Our
      data indicate that left hemisphere decodes human movements conveying semantic
      information, although the specific brain region that is engaged may depend on the
      body part that is moving.

PMID- 15511657
TI  - Effects of handedness and gender on macro- and microstructure of the corpus
      callosum and its subregions: a combined high-resolution and diffusion-tensor MRI
      study.
AB  - The corpus callosum (CC) represents the major commissural tract connecting the
      two cerebral hemispheres and is supposed to play crucial integrative role in
      functional hemispheric specialization. The present study examined whether
      interindividual variations in macro- and microstructure of the human CC are
      associated with handedness and gender. Therefore, a combined diffusion-tensor
      (DTI) and high-resolution morphological MRI study was performed on 34 right- and
      33 left-handed subjects of both sexes. The mid-sagittal surface areas and
      quantitative measures of molecular diffusion (relative anisotropy, mean
      diffusion) of the total CC and its subregions (genu, truncus, posterior third)
      were determined. Analysis revealed a larger total callosal area in right- as
      compared to left-handed subjects and in males as compared to females. Throughout
      all callosal subregions, anisotropy was found to be increased in left-handed as
      well as in male subjects, while the mean diffusion was diminished only in left
      handers. For the posterior third of the CC, a significant negative correlation
      (r=-0.34) between anisotropy and area was detected in right-handed subjects.
      Summarized, significant alterations in the molecular diffusion and in the size of
      the CC with respect to gender and handedness were revealed in the present study.
      These findings can be interpreted as handedness- and gender-related differences
      in macro- and microstructure of the callosal pathways. It was demonstrated that
      the inspection of the callosal microstructure using DTI yields empirical evidence
      on interhemispheric connectivity that goes well beyond the information revealed
      by anatomical measurements alone. Thus, DTI has proven to be a useful additional
      method in cognitive neuroscience.

PMID- 15511658
TI  - Allergy and hypersensitivity: from genes to phenotype.

PMID- 15511659
TI  - Positionally cloned susceptibility genes in allergy and asthma.
AB  - After several years of research to find asthma-susceptibility genes using genome
      wide linkage scans and refined genetic mapping methods, four highly interesting
      candidate genes have recently been reported. Each of these genes represents a
      different functional class, and might point to a new pathway in the pathogenesis
      of asthma. Current research is focusing on confirming the genetic associations in
      diverse populations and understanding the biochemical functions of the proteins.
      These second-generation candidate genes for asthma susceptibility will stimulate
      much research, and might also enable the testing of multigenic models with
      sufficiently large sample sets.

PMID- 15511660
TI  - Regulatory CD4+ T cells and the control of autoimmune disease.
AB  - The immune system is a delicately balanced network of interacting cells. In
      recent years, the concept of immune regulation/suppression has been firmly
      established, and both natural and induced regulatory cells play vital roles in
      protection from autoimmune disease. Recent work has revealed the diverse nature
      of regulatory CD4+ T (Treg) cells and the molecules involved in their function.
      Innate and adaptive responses to infection are able to override the suppressive
      properties of such regulatory cells, whereas several reports point to
      deficiencies in regulatory cell function in autoimmune disease. Protocols have
      been developed that allow the expansion of Treg cells in vitro and their antigen
      specific induction in vivo. A full understanding of Treg differentiation and
      function will facilitate the development of improved strategies for prevention
      and treatment of autoimmune diseases.

PMID- 15511661
TI  - The interplay of dendritic cells, Th2 cells and regulatory T cells in asthma.
AB  - Dendritic cells are essential for Th2 differentiation of naive CD4+ T cells in
      response to aeroallergens, and in recent years it has been well established that
      these cells play a pivotal role in the initiation phase of allergic asthma.
      Dendritic cells are also crucial for maintaining eosinophilic airway inflammation
      by controlling the recruitment and activation of primed Th2 cells in the lung. A
      picture is emerging wherein the balance of pathogenic Th2 cells and regulatory T
      cells is tuned by dendritic cells not only at the initiation but also at the
      effector stage of the allergic immune response.

PMID- 15511662
TI  - Regulation and role of transforming growth factor-beta in immune tolerance
      induction and inflammation.
AB  - Transforming growth factor-beta (TGF-beta) is known to mediate pleiotropic
      functions both inside and outside the immune system. Recent progress in this
      field underlines the role of TGF-beta in regulatory T (Treg) cells, where it
      participates in both suppression and differentiation. In addition, recent
      information highlights the role of TGF-beta in repair responses that lead to
      matrix deposition and tissue remodelling. Many chronic inflammatory diseases,
      such as asthma, profit from the suppression of specific immune responses by TGF
      beta; however, TGF-beta-mediated tissue remodelling can be a serious complication
      in such diseases.

PMID- 15511663
TI  - Apoptosis in tissue inflammation and allergic disease.
AB  - Genetic predisposition and environmental instructions tune thresholds for the
      activation, effector functions and lifespan of T cells, other inflammatory cells
      and resident tissue cells. Defects in apoptosis and peripheral tolerance in T
      cells define different allergic phenotypes. In individuals with atopic allergic
      disease, activated allergen-specific T cells expressing high levels of IFN-gamma
      predominantly undergo apoptosis in the circulation, skewing the immune response
      to surviving T helper type 2 (Th2) cells. In affected tissues, these cells switch
      on effector cytokines and induce the activation and apoptosis of epithelial
      cells. In individuals with non-atopic monoallergic disease, by contrast, a
      disturbed balance towards allergen-specific Th2 cells instead of T regulatory
      type 1 (Tr1) cells characterizes the T cell response.

PMID- 15511664
TI  - Chemoattractants and their receptors in homeostasis and inflammation.
AB  - The study of leukocyte migration continues to provide new insights into the
      regulation of lymphocyte priming in secondary lymphoid organs and effector
      responses in inflamed tissues. Chemoattractant receptors have always been viewed
      as facilitators of cell movement into a tissue. This whole concept must now be
      revised with the discovery of sphingosine 1 phosphate receptors, which control
      cell exit from lymphoid tissues. The chemoattractants that regulate lymphoid
      tissue homing are usually different to those that regulate leukocyte recruitment
      to inflamed tissues. There is evidence, however, of inflammatory pathways of
      leukocyte recruitment in lymph nodes and, conversely of constitutive pathways in
      peripheral tissues. Finally, antagonists (or agonists) of chemoattractant
      receptors and their signalling pathways represent the most attractive strategy
      for the treatment of a wide range of inflammatory diseases, including allergy.

PMID- 15511665
TI  - Cellular mechanisms of T cell mediated drug hypersensitivity.
AB  - Noncovalent drug presentation leads to the activation of drug-specific T cells.
      In some patients with hypersensitivity, such a response occurs within hours even
      upon the first exposure to the drug. Thus, the reaction to the drug might not be
      due to a classical, primary response, but rather mediated by existing,
      preactivated T cells that are cross specific for the drug, and have an additional
      (peptide) specificity as well.

PMID- 15511666
TI  - Autoimmunity: The genes and phenotypes of autoimmunity.

PMID- 15511667
TI  - Regulating self-tolerance by deregulating gene expression.
AB  - Intrathymic expression of peripheral auto-antigens, termed promiscuous gene
      expression, extends the scope of central T-cell tolerance to peripheral organs
      and proves essential for the induction and maintenance of self-tolerance. The
      purification of antigen-presenting cells has been instrumental in identifying
      promiscuous gene expression as an inherent property of medullary epithelial
      cells. The pool of promiscuously expressed genes might encompass up to 10% of the
      whole genome. The remarkable diversity of this gene pool implies a complex mode
      of regulation, which cannot be solely explained by the action of a single factor,
      such as the transcriptional autoimmune regulator AIRE. Co-localization of
      promiscuously expressed genes in clusters also suggests epigenetic mechanisms
      (e.g. DNA methylation) to account for this unorthodox gene expression pattern.
      The identification of the molecular components controlling the expression of
      tissue-restricted genes in the thymus promises to add valuable new insights into
      the complex genetic regulation underlying most autoimmune diseases.

PMID- 15511668
TI  - Aire: an update.
AB  - Aire (autoimmune regulator), the gene responsible for the clinical disorder
      autoimmune polyendocrinopathy syndrome type I, has recently been identified as an
      important mediator of central tolerance. Aire upregulates the transcription of
      certain organ-specific self-antigens in medullary thymic epithelial cells, and
      has a role in the negative selection of organ-specific thymocytes. However, the
      molecular mechanisms by which Aire functions in these processes are still not
      well understood. Structural characteristics and biochemical data suggest that
      Aire might have a direct role in nuclear transcription and that it can function
      as an ubiquitin ligase. Although these molecular details await further
      characterization, the association of Aire with the prevention of autoimmunity
      highlights the importance of thymic mechanisms in the maintenance of tolerance.

PMID- 15511669
TI  - Post-translational modifications of self antigens: implications for autoimmunity.
AB  - Alterations in amino acid sequence can generate neo-epitopes from self proteins,
      causing autoaggressive immune attack. There is a range of possible post
      translational modifications (PTMs) of mammalian proteins that can allow immune
      recognition of neo-self epitopes. These effects can vary from overt increase in
      affinity of MHC or T-cell receptor binding, to more subtle effects on the
      activity of proteolytic enzymes involved in antigen processing. Furthermore,
      intriguing insights into how the complex interactions between inflammation,
      enzyme activity and protein modification can direct self recognition are
      beginning to be unearthed.

PMID- 15511670
TI  - Initiation of autoimmunity.
AB  - It has recently become clear that several factors must coincide for the
      initiation of autoimmunity. At minimum, these involve a genetic predisposition,
      naive lymphocytes that can react with autoantigens and a precipitating event that
      leads to T and/or B cell activation. Inter-individual variations in these factors
      probably explain the significant complexity associated with autoimmune diseases;
      however, quantitative issues are also important because clinical disease will
      manifest only if a sufficient amount of cellular material has been destroyed.
      Therefore, the presence of autoreactive lymphocytes does not always signify
      disease; rather, the kinetics of their generation, their resulting numbers and
      the regulation of their activation and effector functions (destructive versus
      regulatory) will determine the ultimate outcome and make the difference between
      subclinical autoimmunity and disease.

PMID- 15511671
TI  - Regulatory T cells and transcription factors: gatekeepers in allergic
      inflammation.
AB  - Antigen-provoked polarization of CD4+ T cells along the Th1 pathway is often
      associated with autoimmune and chronic inflammatory diseases, whereas extreme
      skewing of the response toward a Th2 phenotype has been linked to atopy and
      allergic diseases. Intense interest in the underlying molecular mechanisms that
      control polarization has revealed a contingent of regulatory transcription
      factors, which not only help to define these pathways but also suggest potential
      sites for interventional tactics. Moreover, the recent identification of
      transcription factors specifically associated with CD4(+)CD25+ regulatory T-cells
      provides new clues regarding manipulation of this population in pursuit of
      directed immune regulation. Continued unraveling of the pathways underlying the
      development of deleterious immune responses and their control will guide new
      avenues of investigation and intervention.

PMID- 15511672
TI  - Homeostasis and T cell regulation.
AB  - Homeostatic regulation of cell numbers is an important principle in biology.
      Mechanisms that function to maintain or re-establish homeostasis in the immune
      system include interactions among antigen-presenting cells, regulatory T cells
      and cytokines. The vital role that homeostatic regulation plays in maintaining a
      functionally intact immune system is illustrated by the perturbation of the
      peripheral T cell repertoire that occurs after lymphopenic incidents, which
      frequently provoke either exacerbated immune or autoimmune responses. Recent
      studies show that transient states of lymphopenia occur in viral infections and
      in the neonatal state and might be involved in the development of autoimmune
      diseases. On the positive side, lymphopenia-provoked T cell expansion might
      enhance weak immune responses and thereby aid the rejection of tumours or the
      elimination of parasites.

PMID- 15511673
TI  - Emerging approaches for the therapy of autoimmune and chronic inflammatory
      disease.
AB  - Progress in defining protein and gene signatures that characterize autoimmune
      mediated inflammatory diseases has uncovered a large number of potential
      therapeutic targets. Preclinical data from rodent models can be generated
      rapidly, as can data from the genetic crosses of gene-deficient mice on
      autoimmune-susceptible backgrounds. But humans are not the same as mice, and
      however robust preclinical data might appear, therapeutic intervention in
      patients with autoimmune disease remains the definitive experiment. Several
      studies published in the past year have tested paradigms of autoimmune disease in
      clinical trials. Recent therapeutic approaches for targeting B-cell subsets and
      co-stimulatory pathways are described here in detail. It is our belief that the
      future of immunotherapy in the clinic will depend to some extent upon the
      availability of biomarkers for defining biological signatures of immune function
      in vivo.

PMID- 15511674
TI  - New insights into disease pathogenesis from mouse lupus genetics.
AB  - Full manifestation of mouse lupus, similar to the human disease in its severe
      form, is characterized by elevated antinuclear autoantibody levels and the
      development of kidney disease. Considerable evidence supports a genetic basis for
      lupus. The functional dissection of susceptibility loci in multigenic mouse
      models of lupus has provided insight into the immune abnormalities associated
      with autoantibody production and other processes critical for inflammation and
      damage in the kidney. The elucidation of models with single-gene manipulations
      has also identified immune mechanisms in the pathway to lupus. Recent advances
      have challenged previously accepted truths and new layers of complexity have
      become apparent.

PMID- 15511675
TI  - Genetics of human systemic lupus erythematosus: the emerging picture.
AB  - Systemic lupus erythematosus (SLE) is a systemic autoimmune inflammatory disease
      with partially understood etiology, which can affect virtually any organ. Despite
      suggestions to the contrary, SLE is proving to be a reliable phenotype for
      genetic studies. Similar to many other autoimmune diseases, SLE demonstrates a
      complex pattern of inheritance that is consistent with the involvement of
      multiple susceptibility genes as well as environmental risk factors. During the
      past several years, some new candidate genes have been implicated in induction of
      SLE through association studies, and multiple susceptibility regions have been
      detected through genome-wide linkage studies. Many of the susceptibility effects
      have been confirmed by independent studies.

PMID- 15511676
TI  - The emerging role of interferon in human systemic lupus erythematosus.
AB  - Recent studies of patients with systemic lupus erythematosus, together with data
      from lupus-prone mice, suggest that inappropriate activation of type I interferon
      might have a role in disease pathogenesis. Serum levels of IFN-alpha are elevated
      in SLE patients, and gene expression profiling of peripheral blood cells shows
      that most lupus cases demonstrate an upregulation of IFN-responsive genes. Of
      interest, the IFN gene 'signature' correlates with more severe disease. The
      available data support a model whereby chromatin-containing immune complexes
      circulating in the blood of lupus patients stimulate leukocytes to produce IFN,
      which perpetuates disease. These emerging insights into the connection between
      IFN and lupus provide a host of new diagnostic and therapeutic opportunities.

PMID- 15511677
TI  - The scope of receptor editing and its association with autoimmunity.
AB  - Random assembly of antibody variable (V), diversity (D) and joining (J) gene
      segments creates a vast repertoire of antigen receptors, including autoreactive
      ones. Three ways that are known to reduce autoreactivity in the B-cell
      compartment include clonal deletion, functional inactivation and receptor
      editing, a mechanism involving a change in antigen receptor specificity through
      continued V(D)J recombination. New data suggest that editing can efficiently
      eliminate autoreactivity, yet, in an autoimmune context, secondary antibody gene
      rearrangements might also contribute to autoimmunity.

PMID- 15511680
TI  - Overview of Japanese experience-controlled and uncontrolled trials.
AB  - Zonisamide is a new type of benzisoxazole derivative, first marketed in Japan in
      1989. This study analyzed: (1) the drug's efficacy by seizure and epilepsy type
      in a total of 1008 patients treated during the development of zonisamide in
      Japan; (2) the effectiveness of zonisamide for 726 newly-diagnosed patients
      treated with zonisamide postmarketing; and (3) 50 patients with generalized
      epilepsies and epileptic syndromes (idiopathic generalized epilepsies,
      symptomatic generalized epilepsies, Lennox-Gastaut syndrome, Doose syndrome, and
      West syndrome), and 19 patients with undetermined epilepsies and specific
      syndromes (refractory grand mal in childhood, severe myoclonic epilepsy in
      infancy, other undetermined epilepsy, familial essential myoclonic epilepsy, and
      mitochondrial encephalomyopathy with ragged-red fibers). Analysis of study
      results showed that among all patients treated, zonisamide was highly effective
      for the treatment of idiopathic generalized epilepsy, temporal lobe epilepsy, and
      other partial epilepsies. The compound was also effective for other symptomatic
      generalized epilepsies. In 50 patients with generalized epilepsies, and 19 with
      undetermined epilepsies and specific syndromes, seizure frequency was reduced by
      >50% with monotherapy or two-drug therapy with zonisamide. Zonisamide was
      effective not only for partial epilepsies and generalized epilepsies but also for
      undetermined epilepsies and specific syndromes such as myoclonus epilepsy.

PMID- 15511682
TI  - Zonisamide monotherapy with once-daily dosing in children with cryptogenic
      localization-related epilepsies: clinical effects and pharmacokinetic studies.
AB  - Clinical effects and pharmacokinetics of once-a-day pediatric zonisamide (ZNS)
      monotherapy were investigated in 72 children (range, 3 months to 15 years; mean
      age, 8 years and 3 months) with cryptogenic localization-related epilepsies with
      simple, complex, or secondarily generalized partial seizures; none had prior
      epilepsy treatment. ZNS was initiated at 2mg/kg; daily dosage was doubled at
      weekly intervals to achieve maintenance dosage (8.0 mg/kg; mean, 7.97 +/- 0.55
      mg/kg). Blood samples determined trough and peak plasma levels; levels were 27.0
      +/- 9.4 microg/ml and 33.8 +/- 10.8 microg/ml, respectively, with ratios as small
      as 1.28 +/- 0.15. Plasma level to dose ratios increased with age; peak-to-trough
      ratios were not age variable. Seizures were not controlled in 23 of 72 patients;
      low trough plasma levels (approximately 15 microg/ml) were observed.
      Drowsiness/short attention span in five patients instigated a dosage decrease
      (peak plasma levels >40 microg/ml). During treatment (6-43 months; mean, 27.2
      months), seizure control occurred in 57 of 72 patients (79.2%), including eight
      refractory patients. In 12 patients with uncontrolled seizures and high ZNS
      levels, carbamazepine (CBZ) was added (BID; mean total dose, 15.1 +/- 3.0 mg/kg)
      to ZNS (QD; mean dose, 11.1 +/- 2.5 mg/kg); drug interactions were examined.

PMID- 15511683
TI  - Review of zonisamide development in Japan.
AB  - Zonisamide is a benzisoxazole-based compound first synthesized in the early 1970s
      by the research laboratories of Dainippon Pharmaceutical Company in Osaka, Japan.
      Identified as an anticonvulsant during exploratory research, zonisamide has since
      been characterized as having broad-spectrum antiepilepsy and neuroprotective
      effects. Early clinical studies in Japan demonstrated that zonisamide has a long
      elimination half-life and is well tolerated; Phase II and III clinical trials
      established the drug's efficacy and safety for the treatment of partial and
      generalized seizures. In 1989, zonisamide was approved and marketed in Japan
      under the trade name of Excegran. Data from postmarketing surveillance studies
      and clinical observations over 10 years of use have continued to support
      zonisamide's efficacy and safety, identified its usefulness as monotherapy, and
      characterized its effectiveness for various seizure types and epilepsy syndromes.

PMID- 15511685
TI  - Effects of zonisamide monotherapy in children with epilepsy.
AB  - This study examined the efficacy and safety of zonisamide as monotherapy in
      pediatric patients with epilepsy. Seventy-seven children with epilepsy (ages 8
      months-15 years) were treated with zonisamide. Nine patients were withdrawn early
      because of side effects; these patients were included in side effect but not
      efficacy analyses. Zonisamide dosages were initiated at approximately 2 mg/kg per
      day and adjusted for each patient individually to a maximum of 12 mg/kg per day.
      Among 44 patients with cryptogenic/symptomatic partial epilepsy, 36 (82%) became
      seizure free; 4 (9%) had a > or =50% reduction in seizure frequency; and 4 (9%)
      had no change in seizures with zonisamide treatment. Of 11 patients with
      cryptogenic/symptomatic generalized epilepsy, 10 (91%) became seizure free, and 1
      experienced no change with zonisamide treatment. Similarly, 4 patients (100%)
      with idiopathic partial epilepsy, and 8 of 9 patients (89%) with idiopathic
      generalized epilepsy became seizure free with zonisamide treatment; in the last
      group, 1 experienced no change. Thirty patients (39%) reported side effects,
      including somnolence (11.7%), decreased spontaneity (7.8%), anorexia (6.5%), and
      rash (6.5%). Thus, zonisamide is effective for partial seizures with or without
      secondarily generalized seizures in children and should be considered a broad
      spectrum antiepilepsy agent.

PMID- 15511687
TI  - Clinical efficacy of zonisamide in childhood epilepsy after long-term treatment:
      a postmarketing, multi-institutional survey.
AB  - Postmarketing data about the effectiveness of zonisamide in childhood epilepsy
      was collected from 759 children with various forms of epilepsy (ages 3 months-15
      years) to compare the long-term efficacy of zonisamide in the treatment of
      epilepsy in intellectually normal versus intellectually disabled children. The
      follow-up period was 6 months-3 years; 291 children (245 intellectually normal,
      46 intellectually disabled) received zonisamide as monotherapy. The remaining
      patients received additional antiepilepsy drugs (AEDs); mean numbers of
      additional AEDs were 1.6 and 2.9 for intellectually normal and intellectually
      disabled groups, respectively. Effectiveness could not be evaluated in 30 of the
      759 patients because of very rare or irregular seizure frequency. In the 729
      patients evaluated, 78% of intellectually normal patients and 43% of
      intellectually disabled patients showed > or =50% reduction in the number of
      seizures (P < 0.001). Improvement rates seen in the intellectually normal group
      were almost the same for patients with generalized (82%) and partial (77%)
      epilepsies, whereas in the intellectually disabled group, the improvement rate
      was higher for partial (50%) than generalized (36%) epilepsies (P < 0.01). These
      results are consistent with the known phenomenon that intellectually disabled
      children are likely to have more intractable seizures than children with normal
      intelligence.

PMID- 15511689
TI  - Efficacy of zonisamide: our experience.
AB  - The current overview of zonisamide use and effectiveness is based on both a long
      term prospective postmarketing survey and current zonisamide use at the Saitama
      Medical College, Department of Neuropsychiatry. Survey data, which were collected
      from individual physicians and 23 survey groups throughout Japan, assessed the
      effectiveness of zonisamide in 1631 patients. Zonisamide was highly effective for
      treating partial seizures, with 70% of patients reporting improvement. More than
      half of patients with generalized seizures (58%) and half of patients with
      myoclonic and atypical absence seizures showed improvement with zonisamide
      treatment. Among the different epileptic syndromes, zonisamide was highly
      effective in treating generalized idiopathic epilepsy (> or =78% improvement) and
      partial epilepsy (> or =58% improvement). However, only 28% of patients with West
      syndrome or Lennox-Gastaut syndrome showed improvement. Among 60 outpatients
      treated with zonisamide at our facility as of October 1998, most had partial
      seizures or generalized seizures subsequent to partial seizures. The majority of
      patients received zonisamide in combination with other antiepilepsy drugs.
      Patients receiving zonisamide monotherapy showed greater improvement than did
      patients receiving polytherapy. We conclude that zonisamide is highly effective
      for partial seizures and generalized seizures, and that there appears to be no
      decrease in efficacy with long-term use.

PMID- 15511691
TI  - Zonisamide: chemistry, mechanism of action, and pharmacokinetics.
AB  - Zonisamide is a synthetic 1,2-benzisoxazole-3-methanesulfonamide with
      anticonvulsant properties. The sulfamoyl group on zonisamide was expected to
      suppress seizures in a manner similar to another sulfonamide analogue,
      acetazolamide, through inhibition of carbonic anhydrase. However, this does not
      appear to be the primary mechanism of action since zonisamide requires much
      higher doses than acetazolamide to achieve equivalent titration in vivo. Studies
      with cultured neurons indicate that zonisamide blocks repetitive firing of
      voltage-sensitive sodium channels and reduces voltage-sensitive T-type calcium
      currents without affecting L-type calcium currents. Its dual mechanism of action
      may explain its efficacy in patients resistant to other antiepileptic drugs
      (AEDs). Zonisamide has a pharmacokinetic profile favorable for clinical use. It
      is rapidly and completely absorbed and has a long half-life (63-69h in healthy
      volunteers) which allows twice-daily, or even once-daily, dosing. Zonisamide is
      not highly bound to plasma proteins. Consequently, it does not affect protein
      binding of other highly protein-bound AEDs. Furthermore, zonisamide does not
      induce its own metabolism and does not induce liver enzymes. However, since
      zonisamide is metabolized by cytochrome P450, liver enzyme-inducing AEDs will
      increase zonisamide clearance, and dosage adjustments may be necessary when it is
      used in combination with certain AEDs.

PMID- 15511692
TI  - Safety of zonisamide therapy: prospective follow-up survey.
AB  - Zonisamide safety was evaluated based on a postmarketing surveillance study of
      patients treated for 1-3 years. Nine hundred twenty-eight children and 584 adults
      (ages 1 month to 79 years), including 372 newly-diagnosed patients, received
      zonisamide for partial and generalized epilepsies. Of the intractable patients,
      1008 received zonisamide in combination with other antiepileptic drugs (AED), and
      52 successfully transitioned to zonisamide monotherapy. A total of 1089 adverse
      events occurred in 476 (31.5%) of 1512 patients. Incidence of adverse effects was
      significantly lower among patients receiving zonisamide monotherapy than in those
      receiving polytherapy: 21% (18.9% of children, 29.4% of adults) versus 35.6%
      (30.4% of children, 41.7% of adults), respectively. The total incidence of
      adverse effects was lower for children (26.2%) than for adults (39.9%). Most
      common adverse events included mental/psychiatric symptoms (19.4%),
      gastrointestinal symptoms (8.7%), and neurological symptoms (5.8%). Effects that
      seemed unique to zonisamide were impairment of mental function, motivation or
      volition, and hypohidrosis. Urinary calculi were detected in only two patients
      (0.13%). Teratogenicity was evaluated in six patients. Two patients on zonisamide
      monotherapy and three on polytherapy delivered normal children. One of four
      patients on polytherapy conceived a fetus with a skull defect with cerebral and
      cerebellar dysgenesis.

PMID- 15511694
TI  - Zonisamide overview of the United States experience.

PMID- 15511695
TI  - Review of United States and European clinical trials of zonisamide in the
      treatment of refractory partial-onset seizures.
AB  - Zonisamide is an antiepilepsy drug (AED) with both sodium and calcium channel
      blocking properties. This dual mechanism may predict efficacy in some refractory
      patients, and a broad spectrum of action against different seizure types.
      Zonisamide has been commercially available in Japan since 1989, and became
      available in the United States for treatment of adults over the age of 12 with
      partial-onset seizures in March 2000. Several multicenter clinical trials have
      been conducted in the United States over the past 15 years. These have included
      three double-blind, placebo-controlled trials as well as long-term open-label
      studies. Zonisamide was characterized in these studies as a safe and effective
      adjunctive treatment for partial-onset seizures. Zonisamide has not yet been
      studied in the United States as an initial monotherapy, but in one long-term
      study, some patients were able to discontinue other AEDs and successfully
      transition to monotherapy. The most frequently reported adverse events were
      somnolence, dizziness, and anorexia. Current United States labeling states that
      12 patients with epilepsy receiving zonisamide had symptomatic kidney stones;
      however, after more than a dozen years of zonisamide use in Japan, the incidence
      of kidney stones associated with zonisamide remains low.

PMID- 15511696
TI  - Zonisamide clinical trials: European experience.
AB  - European clinical trials of zonisamide as adjunctive therapy for refractory
      partial seizures included a 12-week double-blind, placebo-controlled study and a
      15-month open-label extension study. In the double-blind study, patients (n =
      144) were randomized to placebo or zonisamide (400 mg QD) after baseline
      evaluation. Patients completing the double-bind study (n = 115) continued on open
      label zonisamide for up to 18 months. Median percent reduction in partial
      seizures from baseline was significantly greater in zonisamide-treated patients
      compared to those receiving placebo (31.6% versus 3.3%, respectively; P = 0.008).
      Additionally, more zonisamide-treated patients achieved > or = 50% reduction in
      seizure frequency relative to baseline than did placebo patients (30.4% versus
      14.7%, respectively; P = 0.03). The extension study showed that zonisamide
      efficacy was maintained or improved over time. Patient and physician assessments
      favored zonisamide over placebo in terms of patient improvement with treatment.
      Median zonisamide maintenance dosage was 400mg/day, and the average therapeutic
      blood level was 16.9 microg/mL. Both studies showed that zonisamide was well
      tolerated; adverse events were generally mild to moderate and most frequently
      included fatigue, dizziness, somnolence, and anorexia. Collectively, these
      findings corroborate those of US and Asian clinical trials, which also show that
      zonisamide is safe and effective for adjunctive therapy of partial seizures.

PMID- 15511698
TI  - Melatonin, sleep, and circadian rhythms: rationale for development of specific
      melatonin agonists.
AB  - Circadian rhythm sleep disorders (CRSDs), whether chronic or transient, affect a
      broad range of individuals, including many elderly, those with severe visual
      impairments, shift workers, and jet travelers moving rapidly across many time
      zones. In addition, various forms of insomnia affect another large sector of the
      population. A feature common among CRSDs and some forms of insomnia is
      sensitivity to the hormone melatonin, which is secreted by the pineal gland.
      Accumulating evidence suggests that melatonin may regulate the circadian clock
      located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Although the
      light-dark cycle is the primary signal that entrains the circadian clock to
      environmental cycles, exogenous melatonin has been shown to entrain the clock in
      individuals with no light perception and free-running circadian rhythms.
      Furthermore, studies have reported beneficial effects of melatonin for treatment
      of certain insomnias. Together, these studies suggest that melatonin may be
      useful for treating some insomnias and CRSDs. In these contexts, use of melatonin
      as a supplement has been popular in the United States. Unfortunately, the
      therapeutic potential of melatonin has been difficult to realize in clinical
      trials, possibly owing to non-specific actions of the agent and its unfavorable
      pharmacokinetic properties when administered orally. In an attempt to take
      advantage of the therapeutic opportunities available through the brain's
      melatonin system, researchers have developed several melatonin agonists with
      improved properties in comparison to melatonin. Some of these agents are now in
      clinical trials for treatment of insomnia or CRSDs.

PMID- 15511699
TI  - Automated EEG-sleep analyses and neonatal neurointensive care.
AB  - Clinical applications of neonatal EEG-sleep studies can improve neurointensive
      care for preterm and fullterm infants. Behavioral and physiologic assessments of
      neonatal sleep by nursing and physician personnel can result in more
      developmentally appropriate state regulation for infants, particularly for those
      who require medical care for many weeks to months in the intensive care unit.
      Secondly, prediction of altered expressions of EEG-sleep patterns for those
      children at higher risk for neurological sequelae can anticipate the need for
      aggressive interventional strategies. The application of digital analyses of
      specific cerebral and noncerebral physiologic measures for long-term monitoring
      periods can utilize efficient and novel strategies of automated EEG and sleep
      state identification which can also assist in daily medical care and prediction
      of neurodevelopmental outcome.

PMID- 15511700
TI  - Wrist actigraphy in estimation of sleep and wake in intellectually disabled
      subjects with motor handicaps.
AB  - BACKGROUND AND PURPOSE: We studied the applicability of wrist actigraphy to sleep
      wake estimation in patients with motor handicaps. PATIENTS AND METHODS:
      Concomitant polysomnographic and actigraphic recordings (16-24 h) were compared
      in three groups: normally moving subjects with normal sleep (n=10), sleep
      disordered subjects without motor handicaps (n=13) and sleep-disordered patients
      with different motor disabilities (n=16). The motor abilities of the subjects
      were determined by clinical evaluation using a grading scale from 0 to 10. Their
      actual daily activity was calculated from the recordings as average activity
      scores. RESULTS: In the healthy subjects, the mean difference between actigraphic
      and polysomnographic total sleep estimation was negligible (-1 min), while in
      both sleep-disordered groups, sleep was highly overestimated by actigraphy. There
      was a significant correlation between the motor ability score and the discrepancy
      between actigraphy and polysomnography, but individual data points were highly
      scattered. A more consistent correlation was found between the average activity
      score/min in actigrams and the discrepancy of actigraphic with polysomnographic
      total sleep estimation (Spearman's r=-0.58, P=0.0001, n=39). When the recordings
      with very low average activity score were rejected from the analyses (two
      patients without and six with motor handicaps), the overestimation of sleep by
      actigraphy was reduced but it still remained in both sleep-disordered groups. The
      mean differences of total sleep between actigraphy and polysomnography were 72
      and 121 min and the rank order correlation coefficients 0.80 and 0.71 in patients
      without and with motor handicaps, respectively. The median discrepancy in total
      sleep estimation was 6% in both sleep-disordered groups. CONCLUSIONS: In subjects
      with rudimentary motor abilities, a standard actigraphy can produce a signal,
      which is related to the amount of sleep scored in polysomnograms. The sleep
      parameters obtained by the two methods are not equal, however. The inspection of
      actigrams is more reliable than the clinical scaling of motor abilities in
      predicting the applicability of wrist actigraphy.

PMID- 15511701
TI  - Sleep disturbances, pain and analgesia in adults hospitalized for burn injuries.
AB  - BACKGROUND AND PURPOSE: Sleep disturbances are frequently reported in
      hospitalized patients. We have recently shown significant daily relationships
      between poor sleep and acute burn pain during the first week of hospitalization,
      where poor sleep leads to reports of higher pain intensity and in return, greater
      pain affects quality of sleep. This prospective study was designed to objectively
      evaluate sleep disturbances in hospitalized burn patients and further evaluate
      their relationships with pain intensity and administered medication. PATIENTS AND
      METHODS: Sixteen non-ventilated burn patients wore an actigraph (Ambulatory
      Monitoring, Inc.) during hospitalization (N of 24-h observations 164). Sleep
      measures included duration and fragmentation (# of awakenings, mean duration of
      awakenings, mean duration of sleep episodes (MDAW)). Pain intensity was assessed
      at rest (nighttime, morning, during the day) and following therapeutic procedures
      known to be painful (e.g. dressing changes). RESULTS: Although sleep duration was
      extremely variable, patients slept an average of 5.5 h a night with numerous
      awakenings. During the day, patients often took naps, bringing their total sleep
      time (TST) to 8 h. Regression analyses showed significant temporal relationships
      between sleep, pain and analgesic medication such that a night of poor sleep was
      followed by a significantly more painful day and higher analgesic intake.
      Further, high levels of pain and analgesic medication during the day were both
      significant predictors of poor sleep on the following night. CONCLUSIONS: These
      results obtained with objective measures support previous findings that
      subjective sleep quality following burn injuries is poor, and strengthen the
      evidence of a relationship between sleep and sensitivity to pain. Nonetheless,
      further analyses are necessary to determine and dissociate the effects of pain
      intensity and analgesic medication on sleep.

PMID- 15511702
TI  - Correlation between rating scales and sleep laboratory measurements in restless
      legs syndrome.
AB  - OBJECTIVES: The aim of this study was to test the external validity of the
      International Restless Legs Scale (IRLS) by assessment of the correlation between
      IRLS scores and objective measures of severity such as polysomnography (PSG) and
      Suggested Immobilization Test (SIT). DESIGNS: Correlation analysis between rating
      scales for RLS (IRLS and Johns Hopkins RLS Scale--JHRLSS) and sleep laboratory
      measurements in untreated RLS patients. METHODS: The study included 30 untreated
      patients diagnosed with RLS according to the criteria of the International RLS
      Study Group. Diagnostic procedures included physical exam, laboratory analysis,
      PSG and a nocturnal SIT. Statistical analysis was performed by means of
      Spearman's correlations and Kruskal-Wallis test. RESULTS: IRLS correlated
      significantly with Periodic Leg Movement of Sleep-index (PLMS), and PLMS-arousal
      index during PSG as well as with Periodic Leg Movement of Wakefulness (PLMW)
      during SIT (SIT-PLMW) (all r=0.4; p<0.01). There was no correlation between IRLS
      and the number of PLMW in PSG (PSG-PLMW) or any other sleep variable during PSG.
      Nor was any correlation found between IRLS scores and ferritin, age, duration of
      illness or any other clinical variables. CONCLUSIONS: This study represents the
      first demonstration of a correlation between IRLS and objective parameters of
      motor dysfunction such as PLMS-index or SIT. This finding is particularly
      relevant for the design of future clinical trials. Furthermore, the association
      between PLMS and SIT-PLMW supports the view that both PLMS and PLMW might share a
      common mechanism.

PMID- 15511703
TI  - A general automatic method for the analysis of NREM sleep microstructure.
AB  - OBJECTIVE: To define a unified method for the automatic recognition and
      quantitative description of EEG phasic events of sleep microstructure occurring
      during NREM sleep, particularly arousals, phase A subtypes of cyclic alternating
      pattern and spindles. METHODS: The NREM sleep EEG of 10 normal young subjects was
      examined in order to recognize formal phasic events of sleep microstructure. The
      following 'formal' events (i.e. events defined exclusively on the basis of
      automatic analysis criteria) were classified: arousals, A1-phases (A-phases not
      including arousals) and A2- and A3-phases (A-phases including arousals). Spindle
      bursts, corresponding to visually recognized spindles, were also formally
      defined. The identification of these events was carried out following a three
      step procedure: (1) computation of band-related descriptors derived from the EEG
      signal, (2) introduction of suitable thresholds and (3) application of simple
      logical principles, i.e. an exclusion principle and an overlapping principle.
      RESULTS: Formal A-phases, arousals and spindle bursts showed spectral
      characteristics which were consistent with visual inspection. The value of the
      parameter Correctness for the recognition of the A-phases was 83.5%. In
      particular, the different physiological distribution of the A-phases in Stage 2
      preceding slow wave sleep with respect to Stage 2 preceding REM sleep was
      confirmed. CONCLUSIONS: The proposed method provides a unified quantitative
      approach to the study of sleep microstructure. Visually defined events can be
      reliably identified by means of automatic recognition.

PMID- 15511704
TI  - An alternative measure of sleep fragmentation in clinical practice: the sleep
      fragmentation index.
AB  - BACKGROUND AND PURPOSE: Micro-arousals (MA) are commonly considered as sleep
      components reflecting sleep fragmentation. However, their elucidation is time
      consuming, with considerable inter-observer variability. The aim of our study was
      to investigate the usefulness of a sleep fragmentation index (SFI) to detect
      sleep disruption in a large sample of patients. PATIENTS AND METHODS: Five
      hundred ninety-eight polysomnographic studies made in controls and patients were
      examined. The SFI was calculated as the total number of awakenings and sleep
      stage shifts divided by total sleep time. RESULTS: In the whole group a
      significant correlation was found between the SFI and the MA index (MAI)
      (P<0.001) with good agreement across a wide range of values. When patients were
      stratified according to final diagnosis a significant relation was noted for
      patients with insomnia (P<0.001), parasomnia (P<0.001), circadian schedule
      disorders (P<0.001) and sleep related breathing disorders (P< 0.001). Lower
      values were found in controls (P<0.01) and in patients with periodic limb
      movement disorder and/or restless legs syndrome (P<0.05). In 111 patients having
      two consecutive recording nights, a good reproducibility was present with no
      differences between nights (P=ns) and with significant correlation (P<0.001).
      CONCLUSIONS: The SFI seems to be an accurate, reproducible and easy method to
      detect sleep fragmentation in patients with sleep disorders. Further studies are
      needed to validate the usefulness of this tool in clinical practice.

PMID- 15511705
TI  - Idiopathic edema is associated with obstructive sleep apnea in women.
AB  - BACKGROUND AND PURPOSE: This study was undertaken to clarify whether idiopathic
      edema is a marker for obstructive sleep apnea (OSA), independent of level of
      obesity, in patients with normal left ventricular function. PATIENTS AND METHODS:
      Seventy-eight ambulatory, obese, adults, 44 with bilateral, pitting pre-tibial
      edema, and 34 without edema, from an inner city family practice and a suburban
      family practice enrolled from July 1995 until March 2003. Edematous subjects, but
      not non-edematous subjects, underwent echocardiography, urinalysis, and blood
      test evaluations to ensure that cardiac, renal, hepatic, and thyroid functions
      were normal. All subjects underwent spirometry, pulse oximetry on room air, and
      polysomnography evaluations. RESULTS: Compared to the non-edematous subjects, the
      edematous subjects were more obese (body mass index=47.0+/-9.3 versus 36.5+/-4.6
      kg/m2, P=0.002), had more severe OSA (apnea-hypopnea index (AHI)=34.1+/-27.7
      versus 17.0+/-19.4, P=0.002), and had lower oxygen saturations (96.2+/-2.0 versus
      97.1+/-1.5%, P=0.05). Using an AHI > or = 15 as the criteria for diagnosing OSA,
      there was an association between edema and OSA in women (P=0.02) but not men.
      CONCLUSIONS: In subjects with normal left ventricular function, idiopathic edema
      is associated with OSA in women.

PMID- 15511706
TI  - Effect of nasal continuous positive airway pressure on edema in patients with
      obstructive sleep apnea.
AB  - BACKGROUND AND PURPOSE: Previous research has identified an association between
      idiopathic edema and obstructive sleep apnea (OSA) in women, but a causal
      relationship between OSA and edema has not been established. This study was
      undertaken to determine whether nasal continuous positive airway pressure (CPAP)
      lessens edema in patients with idiopathic edema and OSA. PATIENTS AND METHODS:
      This was a case-series study that enrolled eight ambulatory, obese, adults with
      bilateral, pitting pre-tibial edema and OSA from an inner city family practice
      and a suburban family practice from July 1995 until March 2003. Enrollees
      underwent subjective and physical examination assessment of changes in edema
      after initiation of nasal CPAP. RESULTS: All but one of the subjects had severe
      OSA. The edema was typically 1+ to 2+, and the duration of the edema ranged from
      6 months to more than 20 years. Seven of the eight subjects experienced a
      reduction in the amount of edema following nasal CPAP (P=0.04). CONCLUSIONS: In
      subjects with OSA and idiopathic edema, nasal CPAP reduces the amount of edema.
      If valid, these results indicate that OSA can cause edema.

PMID- 15511707
TI  - Hippocampal area metabolites relate to severity and cognitive function in
      obstructive sleep apnea.
AB  - BACKGROUND AND PURPOSE: Obstructive sleep apnea (OSA) is associated with
      intermittent hypoxia and cognitive decrements. As the hippocampus is particularly
      susceptible to hypoxia, we hypothesized that it may show biochemical
      abnormalities, and they may relate to apnea severity. PATIENTS AND METHODS: Eight
      males with OSA and five age-matched controls underwent neurocognitive testing
      before and after polysomnography and proton magnetic resonance spectra were
      obtained from the left hippocampal area of all subjects. RESULTS: In the left
      hippocampal area, N-acetyl-containing/creatine-containing compounds was
      significantly increased in OSA (P=0.04). Inspection of these compounds with
      respect to the water resonance indicated that this was most likely due to a
      decrease in creatine-containing compounds rather than any change in N-acetyl
      containing compounds. Lower levels of hippocampal creatine-containing compounds
      were correlated with worse OSA severity and neurocognitive performance.
      CONCLUSIONS: We suggest the changes in creatine levels in the hippocampal area
      represent adjustments to brain bioenergetics, similar to those seen in ischemic
      preconditioning, and may reflect the different susceptibility of these tissues to
      hypoxic damage in OSA.

PMID- 15511708
TI  - Do periodic leg movements influence patients' perception of sleep quality?
AB  - BACKGROUND AND PURPOSE: Periodic leg movements in sleep (PLMS) are a common
      finding in various sleep disorders. Whether PLMS are an epiphenomenon or are
      causally related to the presence of sleep-wake disturbances is still being
      debated. We investigated the relationship of the occurrence of PLMS to patients'
      perception of sleep quality during a night of polysomnography in various sleep
      disorders. METHODS: The retrospective evaluation included PLMS recordings over
      two nights of 78 consecutive patients diagnosed with a restless legs syndrome,
      primary insomnia or insomnia associated with a psychiatric disorder. The
      subjects' perception of sleep during the polysomnography night was assessed by
      the subscale 'sleep quality' of the validated self-rating sleep questionnaire SFA
      (SFA-SQ). RESULTS: SFA-SQ scores correlated with the PLMS index (number of PLMS
      per hour of sleep) only in patients with restless legs syndrome during the first
      of the two nights investigated (r=-0.464, P<0.01). PLMS appear to have a low
      impact on the subjects' perception of sleep quality. The correlation of
      subjective sleep quality to PLMS index in the first of the two investigated
      nights in RLS patients may reflect an adaptation effect. CONCLUSION: The results
      of our study favor the hypothesis that PLMS most likely are not the primary cause
      of sleep disturbances in these patient groups.

PMID- 15511709
TI  - Easy listening to sleep recordings: tools and examples.
AB  - BACKGROUND AND PURPOSE: To specify a simple conversion of neurophysiological
      signals contained in sleep recordings into standard audio files and to illustrate
      how our cerebral audio processor can then detect specific signal characteristics.
      METHODS: A software package (freely accessible from the Internet) has been
      developed that converts signals from standard EDF (or EDF+) format to standard
      audio (WAV) format, a process usually called audification. The software has been
      applied to sleep EEG, EOG and ECG. The software is easy to apply. RESULTS: A wide
      range of audified signals is described, stressing the analogy with familiar
      sounds. Audio properties of EEG in different sleep stages, EOG, ECG and
      respiration signals are discussed. Auditive presentation of the signals invokes
      brain processes that differ essentially from the commonly applied visual
      interpretation, including physiological frequency analysis. CONCLUSIONS: Such
      auditive interpretation may complement the visual one. The widespread use of EDF+
      and multimedia computers makes such audification simple and straightforward.

PMID- 15511710
TI  - Obstructive lingual thyroid causing sleep apnea: a case report and review of the
      literature.
AB  - Lingual thyroid has been reported to cause obstructive sleep apnea (OSA) only
      once in the literature. We present a case of a 49-year-old nonobese female with a
      2-year history of progressive snoring, apneas, snort arousals, and daytime
      somnolence associated with the sensation of an 'enlarging tongue'. She was found
      to have severe OSA caused by a large lingual thyroid. While positive airway
      pressure therapy was not successful, surgical resection of the thyroid was
      curative. OSA caused by lingual thyroid and other oropharyngeal/parapharyngeal
      tumors are discussed. A careful oropharyngeal examination is important in
      evaluating patients with complaints of OSA.

PMID- 15511711
TI  - Effects of zolpidem and temazepam on driving ability.

PMID- 15511713
TI  - Alcohol, IgE and allergy.
AB  - Alcoholic drinks are involved in a variety of hypersensitivity reactions. These
      include flushing syndrome, anaphylactoid reactions (urticaria/angioedema and even
      shock), as well as the triggering of asthma, food allergy or exercise-induced
      anaphylaxis in susceptible subjects. In addition, there is increasing evidence
      that alcohol intake may play a role as a promoter of the development of
      immunoglobulin-E (IgE)-mediated hypersensitivity to different allergens. It seems
      clear that alcohol intake (alcohol abuse and even moderate alcohol consumption)
      is associated with increased total serum IgE levels. Similarly, alcohol intake
      may be associated with allergic (IgE-mediated) sensitization to environmental
      allergens. The clinical significance of these facts is probably moderate. The
      mechanisms by which alcohol can influence IgE responses are not entirely known,
      but further developments in this area could increase the understanding of both
      allergic diseases and alcohol-induced alterations in the immune system.

PMID- 15511714
TI  - Neuroendocrine pathways of addictive behaviour.
AB  - Alcohol intake is known to modulate plasma concentrations of neuroendocrine
      peptides. However, recent results suggest that the endocrine system may not only
      respond passively to alcohol intake but that, vice versa, it also actively
      modulates alcohol intake behaviour. The most coherent body of data concerns the
      hypothalamo-pituitary-adrenocortical (HPA) axis, with low corticotrophin
      releasing hormone (CRH) being associated with more intense craving and increased
      probability of relapse after acute detoxification. Leptin, beta-endorphin and
      atrial natriuretic peptide (ANP), which indirectly regulate the HPA system, also
      may modulate the intensity of craving or the intensity of the alcohol withdrawal
      syndrome. Although most of the currently available data demonstrate association
      rather than causality between neuroendocrine changes and alcohol-related
      behaviours, they do provide testable hypotheses and open up perspectives of
      treating alcohol dependence via manipulation of the neuroendocrine axis.

PMID- 15511715
TI  - Leptin is associated with craving in females with alcoholism.
AB  - The appetite and weight regulating peptide leptin was associated recently with
      alcohol craving during withdrawal. Nevertheless, correlations were only
      significant with craving displayed on the visual analogue scale for maximum
      craving during the previous week (VAS), and not if assessed with the highly
      validated Obsessive Compulsive Drinking Scale (OCDS). The objective of the
      following study, therefore, is to elucidate further the associations between the
      leptin system and craving concepts during alcohol withdrawal. A sufficiently
      large sample size should allow multiple statistical subgroup and confounder
      analyses. We prospectively investigated 102 chronic alcoholic inpatients (23
      females, 79 males) during withdrawal on days 0 (admission), 1, 2 and days 7-10.
      In addition to the statistical analysis of the total sample, females and males
      were to be analysed separately. For detecting associations between leptin levels
      and craving scores multiple regression analysis was performed. Plasma leptin
      levels were determined, and craving for ethanol was assessed by both the OCDS and
      the VAS. Leptin plasma levels significantly increased during alcohol withdrawal
      compared to day 0, while all craving scores decreased. Body mass corrected leptin
      plasma levels predicted craving on day 0 in the OCDS total score (R=0.55, F=7.91,
      df=1.19, p<0.05) and in the OCDS obsessive subscore (R=0.57, F>=8.48, df=1.19,
      p<0.05) in females. Neither in males nor in the total population did multiple
      regression analysis reveal any significant results. Leptin levels seem to change
      during inpatient alcohol withdrawal. In a multivariate model, correlations
      between leptin levels and the highly validated craving scores of the OCDS can
      only be assumed in females. Hence, gender differences have to be taken into
      account when searching for neurobiological models of alcohol craving.

PMID- 15511716
TI  - The dopamine D2 receptor C32806T polymorphism (DRD2 Taq1A RFLP) exhibits no
      association with smoking behaviour in a healthy UK population.
AB  - A single nucleotide polymorphism (SNP) in the Taq1A site near the DRD2 gene has
      been associated in several studies with smoking behaviour. We genotyped 732
      current smokers (241 low, one to nine cigarettes a day, 250 mid, 10-19
      cigarettes, 241 high, 20+cigarettes) and 243 never-smokers at this site
      (C32806T), to test for effects on smoking initiation and amount of tobacco
      consumed. No significant association between minor allele frequency and smoking
      status was detected. Multiple regression analysis including DRD2 genotype, sex,
      age and alcohol consumption as predictors showed that level of cigarette
      consumption was associated with sex (p=0.003) and age (p=0.002) but not with
      alcohol consumption (p=0.25) or DRD2 genotype (p=0.76).

PMID- 15511717
TI  - Zyban for smoking cessation in a general practice setting: the response to an
      invitation to make a quit attempt.
AB  - The objective of this study was to assess the feasibility and success of Zyban as
      part of a moderately supported smoking cessation programme within UK general
      practice. Treatment was offered to 479 moderately dependent smokers (smoking 15
      or more cigarettes per day) who had never used Zyban, and who had taken part in a
      previous NRT trial (the PATCH study). Main outcome measures were point prevalence
      and continuous abstinence from smoking at 6 and at 12 months. Two hundred and
      forty were excluded because of medical reasons or prescribing contraindication.
      Of the remainder (n=239) only 54 (23%) made an active quit attempt. Thirty
      percent (16/54) were abstinent at six months, and 22% (12/54) at 12 months
      (biochemically validated point prevalence rates). Age, socio-economic status,
      nicotine dependence, and genetic profile appeared to have little impact on
      success rates, but male quit-attempters were significantly more successful than
      female (40% vs. 10% at 12 months, p<0.05). In conclusion, a real-world smoking
      cessation programme using Zyban with moderate support within a general practice
      setting may achieve satisfactory quit rates without widening existing disparities
      in cessation.

PMID- 15511718
TI  - Relation of genotypes of alcohol metabolizing enzymes and mortality of liver
      diseases in patients with alcohol dependence.
AB  - The aim of this study was to investigate the relationship between alcohol
      metabolizing enzyme genotypes and mortality risk of liver diseases among patients
      with alcohol dependence. A total of 130 male patients with a DSM-III-R diagnosis
      of alcohol dependence (mean age 40+/-10 years) were recruited consecutively to
      the study from 1994 to 1995. Blood biochemistry and hepatitis B viral surface
      antigen (HBsAg) were measured. The genotypes of ADH2, ADH3 and ALDH2 were
      determined by polymerase chain reaction and restriction fragment-length
      polymorphism. The mortality cases were identified by matching data files of the
      death certification system of the National Department of Health issued from 1994
      to 2001. Mortality analysis revealed that 58 of 130 cases (45%) died during the
      follow-up period. Among them, 21 cases died of liver diseases. Mortality was not
      higher in HBsAg positive than in negative subjects. The genotypes of alcohol
      metabolizing enzymes are not associated with the mortality risk of liver
      diseases. The small sample size was a limitation of this study. How functional
      genetic polymorphism of the alcohol metabolizing enzymes causes liver damage is
      still not clear. Continuous study of this topic is necessary.

PMID- 15511719
TI  - Gender difference in the pancreatic trypsinogen response to ethanol withdrawal in
      rat pups.
AB  - This study was designed to examine the effects of ethanol withdrawal on offspring
      rats that consumed ethanol during gestation and lactation, in order to examine
      whether there was an improvement in pancreatic trypsinogen and lipase activities
      at 2 months postpartum with respect to offspring that fed on ethanol until death.
      A second purpose for our study was to determine if a folic acid supplement during
      gestation and lactation was sufficient or insufficient to reverse the negative
      effects of ethanol consumption. Both genders were used with the aim of
      investigating any differential pancreatic behaviour. The animals were randomized
      into five groups: the control group (CG) received water and a basic rat diet
      during pregnancy, lactation and growth; the ethanol group (EG) was fed an ethanol
      diet during pregnancy, the suckling period and growth until death; the ethanol
      water group's (E+WG) ethanol was eliminated after lactation; The ethanol-folic
      acid group (E+FG) received a folic acid supplemented diet during pregnancy and
      the suckling period and in the ethanol+folic acid group (E+FG+FG) this
      supplementation continued during growth. Our results showed that ethanol
      administration or ethanol withdrawal did not significantly alter lipase activity
      in the pancreas. Ethanol administration decreased trypsinogen levels in the
      pancreas of males and females. However, in males, as opposed to females, the
      withdrawal of ethanol did not recover the values of pancreatic trypsinogen
      content, nor did a folic acid supplementation significantly alter the parameters
      we studied. Our treatment produced no effect on lipase levels. There was a gender
      related difference in pancreatic trypsinogen content, the implication being that
      in future all results on exocrine pancreas function in male and female animals
      should be analysed separately.

PMID- 15511720
TI  - Cardiorespiratory function in stable methadone maintenance treatment (MMT)
      patients.
AB  - Patients in methadone maintenance programmes (MMT) often smoke tobacco and
      cannabis and many have ongoing illicit drug use. There is therefore potential for
      these patients to have abnormal cardiorespiratory function; however, few studies
      address this in stable MMT patients. We assessed resting cardiorespiratory
      function on 50 stable MMT patients (25 males, 25 females). Forty-six MMT patients
      were current tobacco smokers, 19 were current cannabis users and none were
      currently using opioids other than prescribed methadone. We defined abnormalities
      of respiratory function as those results outside the 95% confidence interval of
      reference values for normal subjects adjusted for age, weight, height and sex.
      Thirty-one (62%) MMT patients had reduced carbon monoxide transfer factor
      (D(L)CO); 17 (34%) had elevated single breath alveolar volume (V(A)) and 43 (86%)
      had a reduced D(L)CO/V(A) ratio. Six patients (12%) had reduced FEV1; one (2%)
      had reduced FVC; and nine (18%) had an obstructive ventilatory defect. Ten (20%)
      patients had PaCO2 higher than 45 mmHg and 14 (28%) had alveolar to arterial
      oxygen gradient (A-aPO2) higher than 15 mmHg. CXR, Echocardiography and ECG
      showed no significant abnormalities. We conclude that stable MMT patients have
      abnormalities of resting respiratory function which may be due to ongoing tobacco
      cigarette and current or past cannabis smoking.

PMID- 15511721
TI  - Seasonal variation in suicides and in deaths by unintentional illicit acute drug
      intoxications.
AB  - In order to assess whether substance-abusing people show a higher risk of dying
      from unintentional acute intoxication in specific periods of the year, and
      whether this unevenly distributed risk is subject to the same seasonal influences
      observed in suicide cases, we studied a total of 15,792 drug-related deaths
      (males=14,259; females=1533) and 20,332 deaths by suicide (males=15,571;
      females=4761), ascertained in Italy among 15-44-year-old people from 1984 to
      2000. Distribution of deaths by month was studied with circular statistic
      techniques, based on the maximization of mean vector length method and the
      Rayleigh test. The monthly distribution of deaths over the study period followed
      an uneven trend that clearly differed, however, between the two time-series
      characterizing suicides and drug-related deaths. A clear seasonal variation was
      found for suicides in both genders, recurring on a significant circannual cycle.
      No circannual cycle was observed in the monthly distribution of drug-related
      deaths, which seem to be influenced by non-casual oscillations following a thrice
      yearly cycle, linked to a significantly more evident 6-month recurrence. Some
      periods of the year, however, are clearly and consistently linked to an enhanced
      risk of dying by unintentional, acute intoxication by illicit drugs.

PMID- 15511722
TI  - Strain-specific responses of inbred mice to ethanol following food shortage.
AB  - Specific inbred mouse strains such as C57BL/6J and DBA/2J show differences in
      consumption of and reaction on drugs of abuse. For example, C57BL/6J mice
      voluntarily consume greater amounts of ethanol than DBA/2J mice. Recently, it
      could be shown that a short environmental experience--12 days of food shortage
      followed by a recovery period--has a strong impact on strain-specific reactions
      to amphetamine. The purpose of the present study was to examine whether food
      shortage experience has an effect on ethanol responses. The effect of a period of
      12 days food restriction which resulted in a weight loss of 20% body weight and
      which was followed by a complete recovery period was studied on ethanol self
      administration and ethanol-induced locomotor activity in C57BL/6Ico and DBA/2Ico
      inbred mouse strains. The experience of food shortage led to a higher ethanol
      intake and preference in C57BL/6Ico mice compared to control animals without food
      shortage experience. In contrast DBA/2Ico showed no difference in ethanol intake
      or preference following this experience. The effect of ethanol onto locomotor
      activity of both mice strains was affected only in the case of DBA/2Ico mice,
      where food shortage experience resulted in a significantly higher ethanol-induced
      locomotor activity. The present data show that in inbred mouse strains
      environmental experiences can have a strong impact onto the effects of ethanol.
      In conclusion, in the field of preclinical alcohol research gene x environment
      interactions in specific inbred mouse strains can contribute strongly to the
      outcome of studies and more specifically food shortage can profoundly affect the
      outcome of alcohol studies in mice.

PMID- 15511725
TI  - Recruitment and retention of an online sample for an HIV prevention intervention
      targeting men who have sex with men: the Smart Sex Quest Project.
AB  - There is an increasing interest in developing interventions for HIV and STD
      prevention that can be delivered on the Internet. However, we know little about
      what it takes to identify, recruit and retain participants in interventions so
      that we can test their efficacy and effectiveness. Objectives for this
      investigation were to evaluate rates of recruitment and retention in an Internet
      based randomized controlled trial (RCT) to increase sexually transmitted disease
      (STD) prevention among men who have sex with men (MSM). The Smart Sex Quest study
      was a RCT conducted online. Eligible participants were MSM, at least 18 years old
      and US residents. After completing a baseline risk assessment, participants were
      exposed to tailored or control messages and asked to return to the site at three
      months for a follow-up interview. From January 2002 through June 2003, 3,625
      persons logged on as potential study participants; of these, 563 were not
      eligible, while 1,286 left the site without filling out a baseline survey.
      Complete baseline data were available for 1,776 participants, all of whom were
      eligible to complete a follow-up. Complete follow-up data were available for 270
      (15.2%) participants. While the Internet is a valuable tool for conducting
      research, conducting this longitudinal research online was severely affected by a
      loss to follow-up, and analyzing outcome data was hampered by significant
      differences between those who did and did not complete the study. Alternate ways
      to recruit for and evaluate online trials must be considered.

PMID- 15511726
TI  - Reflecting on the experience of interviewing online: perspectives from the
      Internet and HIV study in London.
AB  - This paper considers some of the strengths and weaknesses of conducting
      synchronous online interviews for qualitative research. It is based on a study
      among gay/bisexual men that used both qualitative and quantitative methods to
      explore the association between seeking sex through the Internet and HIV
      transmission risk. Between June 2002 and January 2004, 128 gay/bisexual men
      living in London were interviewed one-to-one by the first author (MD) about their
      experience of using the Internet to find sexual partners and negotiating condom
      use for anal sex. Thirty-five men were interviewed online, while 93 were
      interviewed face-to-face (i.e. offline). This paper draws on MD's experience of
      conducting these interviews--both online and face-to-face. Synchronous online
      interviews have the advantage of being cheap, convenient and attractive to people
      who do not like face-to-face interviews. However, some of the social conventions
      and technical limitations of computer-mediated-communication can introduce
      ambiguity into the online dialogue. To minimize this ambiguity, both interviewer
      and interviewee have to edit their online interaction. One of the distinctive
      features of the online interview is that it emerges as a form of textual
      performance. This raises fundamental questions about the suitability of the
      synchronous online interview for exploring sensitive topics such as risky sexual
      behaviour.

PMID- 15511727
TI  - The Internet as recruitment tool for HIV studies: viable strategy for reaching at
      risk Hispanic MSM in Miami?
AB  - Although use of the Internet as a vehicle for HIV/STI research is increasing, its
      viability to recruit at-risk populations such as Hispanic men who have sex with
      men (HMSM) to participate in community-based HIV studies is in its infancy. We
      report on the first 171 participants enrolled in an ongoing study exploring use
      of the Internet to recruit Hispanic men who have sex with men (HMSM) living in
      Miami-Dade County, Florida to participate in community-based studies. We report
      our initial success with chat-room recruitment and describe the sexual and drug
      use practices of the initial set of participants who were recruited through the
      Internet. In addition, we describe the formative work conducted to develop the
      Internet recruitment procedures we are testing. In two months, we spent 211 hours
      recruiting in chat-rooms and engaged 735 chatters. One hundred and seventy-six
      men came to our community sites; 172 (98%) were eligible and completed an audio
      computer-assisted self-interview. In the previous six months, 94.7% of
      participants had anal sex; 48.9% did not use condoms for anal sex or used them
      inconsistently; and 48.5% had used club drugs. Six-month use rates for individual
      drugs were: poppers (31.6%), cocaine (15.8%), ecstasy (14%) and crystal
      methamphetamines (11.7%). Use of club drugs was significantly associated with
      unprotected insertive and unprotected receptive anal sex. These initial findings
      point to the Internet's potential as a tool for recruiting at-risk Hispanic MSM
      for community studies.

PMID- 15511728
TI  - Internet-based site-specific interventions for syphilis prevention among gay and
      bisexual men.
AB  - Recent increases in syphilis in gay men in urban areas in the US and Europe have
      been associated with men meeting new sex partners on the Internet in chat-rooms
      and at websites that facilitate partner meeting. In response to the syphilis
      epidemic in San Francisco, the San Francisco Department of Public Health
      partnered with a community-based organization, Internet Sexuality Information
      Services, Inc., to develop, implement and evaluate a broad range of innovative
      Internet-based prevention interventions including the creation of a website,
      individual online outreach, banner advertisements, chats, an educational site,
      message boards, warnings and an online syphilis testing program. This paper
      documents the varied success of these interventions with process measures and
      calls for greater emphasis on impact measures in the evaluation of these types of
      intervention.

PMID- 15511729
TI  - The Internet Alert Project: spreading the word about high-risk sexual activities
      advertised on the Internet.
AB  - The Internet is an emerging venue for facilitating high-risk sexual behavior; in
      particular, use of the Internet to seek out sex partners has been shown to be
      associated with high-risk sexual behaviors, such as an increase in number of
      sexual partners and an increase in anal sex, which can increase the risk of
      contracting and transmitting sexually transmitted diseases (STDs) including HIV.
      In an effort to assist health departments around the country, the Internet Alert
      Project was developed to provide Centers for Disease Control and Prevention (CDC)
      project officers and field staff with information about Internet-advertised, high
      risk sexual activities in areas that do not have access to sexually explicit
      material on the Internet. An evaluation was conducted to determine the utility of
      the Internet Alert Project, its effect on knowledge and awareness of recipients
      and on public health efforts. Results of the evaluation show the alerts are a
      useful and valuable tool. The alerts have helped to increase knowledge about
      sexually-related uses of the Internet and have also driven public health efforts
      in the field. The results also indicate the need for project areas to access
      information found on the Internet in order to keep up with the ever-changing
      behaviors of at-risk populations.

PMID- 15511730
TI  - Talking about STD/HIV prevention: a look at communication online.
AB  - Little is known about the quality and usability of online health information.
      This analysis evaluated STD prevention websites' content quality and usability.
      Thirty-six sites were analyzed to determine their adherence to established sexual
      health guidelines and their accessibility, usability, credibility and currency.
      The objective of this study was to determine what communication skills are
      available to teenagers through STD prevention websites. Only two (6%) addressed
      safe sex negotiation; seven (19%) addressed basic communication skills; and
      slightly more than half (53%) addressed at least one sexual decision-making
      message. Most sites displayed consistent template design and two-thirds had
      working hyperlinks. But few (19%) of the sites offered a site map, while only one
      third (36%) provided an internal search engine. These results indicate that
      health educators need to include tips on how to negotiate safe sex and improve
      interactive design features when creating STD websites for teenagers.

PMID- 15511731
TI  - Use of gay Internet sites and views about online health promotion among men who
      have sex with men.
AB  - In May-June 2002, 4,974 men who have sex with men (MSM), average age 31 years,
      completed a self-administered questionnaire online accessed through two popular
      gay Internet sites in the UK (gaydar and gay.com UK). Most men were white (95%),
      employed (83%), lived in the UK (91%) and self-identified as gay (85%). Nearly
      half (46%) had not been tested for HIV, while 6% said they were HIV-positive. One
      third (31%) reported high-risk sexual behaviour in the previous three months,
      i.e. unprotected anal intercourse with a partner of unknown or discordant HIV
      status. Nearly all the men (82%) had looked for a sexual partner on the Internet
      and three-quarters had been doing so for more than a year. Almost half the men
      (47%) said they preferred to meet men through the Internet rather than in bars or
      other 'offline' venues. Although nearly 40% of men said the most important reason
      for using these Internet sites was to find sexual partners, a further 17% said
      they primarily used them to have contact with other men, 16% because they were
      bored, 12% for entertainment, 4% because they were lonely and 3% because they
      were addicted to it. The majority of men in this survey had favourable attitudes
      towards online health promotion. Most men thought that Internet sites should
      allow health workers into chat-rooms (75%); would click on a banner to find out
      about sexual health (78%); and said if they met a health worker in a chat-room
      they would find out what they had to say (84%). In multivariate analysis, being
      HIV-positive, older age and high-risk sexual behaviour were all independently
      associated with an increased frequency of using the Internet to look for sex
      (p<0.05). The Internet has emerged as an important meeting place for men who have
      sex with men. As online HIV prevention initiatives are developed it will be
      important to monitor the extent to which the favourable attitudes seen here are
      reflected in preventive behaviours.

PMID- 15511732
TI  - Beliefs about cybersex and Internet-mediated sex of Latino men who have Internet
      sex with men: relationships with sexual practices in cybersex and in real life.
AB  - Cybersex (engaging in sexual self-stimulation while online with another person)
      and meeting partners for sex are commonly reported among men who have Internet
      sex with men (MISM). We studied 1,026 Latino MISM in the US and constructed a
      scale to measure beliefs about cybersex. Respondents were recruited to an online
      Internet study and compensated for their effort. Factor analysis indicated that
      there were three dimensions: (1) liking cybersex: perceived anonymity and safety
      of cybersex; (2) potential for greater IRL interaction in seeking partners on the
      Internet; and (3) a dimension of negative beliefs about Internet contacts which
      was not psychometrically stable. Safety referred to physical and HIV-related
      safety. We formed two scales to describe the first two dimensions. Respondents
      who were high on the 'liking cybersex: perceived anonymity and safety' scale were
      more likely than low scorers to use chat-rooms and webcams. They were also more
      likely than low scorers to have had cybersex and phone sex before meeting. Those
      who were high on the 'IRL interaction' scale were more likely than low scorers to
      use e-mail, bulletin boards and paid websites. However, there was significantly
      less disclosure about HIV status and discussion about safer sex by those higher
      on the 'IRL interaction scale', and when sex in real life did occur, those higher
      on the 'IRL interaction' scale were more likely to have receptive oral or anal
      sex, whereas those high on the 'liking cybersex: perceived anonymity/safety'
      scale were less likely to have insertive sex or be drunk/high. MISM scoring high
      on the 'IRL interaction' scale were significantly more likely than low scorers to
      prefer to meet partners on the Internet. We discuss the implications of the
      Internet for MSM and for sexual IRL interactions in the Internet age.

PMID- 15511733
TI  - The process of seeking sex partners online and implications for STD/HIV
      prevention.
AB  - Research has shown that online sex-seeking among men who have sex with men (MSM)
      is related to elevated risk for sexually transmitted diseases (STDs), including
      HIV infection; however, the process of seeking sex online is not well understood.
      It is important to understand the process of seeking sex partners in order to
      determine the best method for reaching MSM at high risk for infection. We report
      on baseline data from the Smart Sex Quest, an Internet-based STD prevention
      intervention targeting MSM (n = 1,776, 79% white, mean age = 33 years). Results
      indicate that older, white, college-educated men solicited sex partners on AOL,
      whereas Gay.com was a more frequent choice among younger men. Yahoo was named as
      a solicitation site more frequently by those with no college education, as were
      'bareback' websites devoted to facilitating anal sex without the use of condoms.
      Following online solicitation, men tended to meet in public restrooms (86%),
      partners' homes (74%) and their own home (57%). Though results are limited by the
      self-selected nature of the sample, the data have important implications for
      online outreach, study recruitment and intervention.

PMID- 15511734
TI  - The use of the Internet by gay and bisexual male escorts: sex workers as sex
      educators.
AB  - While prior studies have targeted street-based male sex workers as potential
      vectors of disease transmission, the number of men who work independently through
      Internet chat-rooms and other online endeavors has steadily increased. It is
      likely that these men differ substantially from their street-based counterparts
      in terms of sexual risk behaviors with their clients. The purpose of this study
      was to explore the ways in which the Internet has impacted the work of male
      escorts and their sexual practices with clients. Semi-structured qualitative
      interviews and quantitative surveys were administered to 46 such men. Less than
      half the men reported unprotected anal sex with clients. The qualitative data
      lend support to this finding, in that the majority talked about refusing any
      unsafe sex with clients, and many reported taking the extra step of educating
      their clients about the dangers of risky sex. Some of the escorts described the
      methods used to incorporate safer sex practices into sessions with their clients.
      Internet-based male escorts can play an important role as potential sex educators
      on the front lines of the fight against HIV and other sexually transmitted
      infections.

PMID- 15511735
TI  - Substance use and high-risk sex among men who have sex with men: a national
      online study in the USA.
AB  - This paper describes drug and sexual risk behaviors during a six-month period in
      2001 of 2,916 gay and bisexual men who were recruited online. Bivariate and
      multivariate analyses examined correlates of unprotected anal intercourse (UAI).
      Drug and alcohol use were also examined by US region. UAI was associated with
      using alcohol or drugs, including poppers, crystal methamphetamine, cocaine,
      marijuana and Viagra before or during sex. Meeting sex partners both online and
      offline and having multiple sex partners were also predictive of UAI. Significant
      regional differences were seen in the prevalence of drug use and alcohol use.
      Findings are discussed in relation to the need to integrate messages about the
      relationship between drug use and sexual behavior into HIV prevention programs.

PMID- 15511736
TI  - Are the Health of the Nation Outcome Scales (HoNOS) useful for measuring outcomes
      in older people's mental health services?
AB  - The Health of the Nation Outcome Scales (HoNOS) were developed to provide a
      single index in order to enable the government target 'to improve significantly
      the health and social functioning of mentally ill people' to be quantified. They
      were intended to be applicable to all adults (including older people), across a
      wide range of settings so that services in different localities could be compared
      and changes both within individuals and within services could be measured. In
      1999 the HoNOS65+ was launched with a modified glossary for older people. The
      HoNOS has been formally adopted as the preferred outcome measure for adults of
      working age. There has been no such formal adoption of the HoNOS65+, or any other
      outcome measure, for mental health services for older people. This review
      summarises how the HoNOS was originally developed and validated. Studies with
      older people, which have used both the original definitions and those developed
      for the HoNOS65+ are reviewed focusing on data on the reliability and validity of
      the HoNOS and HoNOS65+ with older people. Finally the question of whether the
      HoNOS or HoNOS65+ is suitable as an outcome measure in routine clinical practice
      in services for older people is addressed.

PMID- 15511737
TI  - Screening post-stroke depression in Chinese older adults using the hospital
      anxiety and depression scale.
AB  - Little is known about the performance of the Hospital Anxiety and Depression
      Scale (HADS) in screening post-stroke depression (PSD) in Chinese older adult
      patients. One hundred Chinese geriatric patients with first-ever stroke,
      consecutively admitted to a rehabilitation facility, were assessed by
      occupational therapists using the depression subscale of the HADS. Psychiatric
      diagnoses, which served as the benchmark for judging the usefulness of HADS in
      screening PSD, were made using the Structured Clinical Interview for DSM-III-R
      (SCID-DSM-III-R) supplemented by all available clinical information. The optimal
      cut-off point of HADS was 6/7. The sensitivity, specificity, positive and
      negative predictive value of the HADS, and the area under the receiver operating
      characteristic curve, were 88%, 53%, 0.28, 0.96 and 0.75, respectively. The HADS
      does not appear to be a useful tool in screening for PSD in Chinese older adults.

PMID- 15511738
TI  - Detection of depression and anxiety disorders by home care nurses.
AB  - Several studies have reported that psychiatric disorders, mainly depression and
      anxiety disorders, were masked and undiagnosed among older adults, particularly
      frail elderly. This phenomenon could have a significant impact on elderly quality
      of life. In this study, we assessed the utility of three measures for detecting
      mental health disorders among frail elderly receiving home care services: (1) the
      PRIME-MD; (2) a standard psychological distress measure (PDI-29), and (3) the
      health care case manager'sa priori judgment on the subject's mental health
      status. Results obtained by home care nurses were compared to those obtained by
      clinical psychologists using a structured diagnostic interview (SCID for DSM-IV).
      The study was conducted in two community health service centres. During the
      study's period, all patients in the health care workers' caseload without
      cognitive impairment and not reporting significant stressful life events during
      the six-week period preceding the interview (n = 315) were asked to participate
      in the study. Results showed that 42.9% of the volunteers that agreed to meet a
      psychologist at home (n = 177) had a current SCID-IV diagnosis. The specificity
      of the PRIME-MD test performed by nurses was 83.8% and its sensitivity was 41.7%.
      The correct classification rate was 66.7%. Results indicated that the PDI-29
      items showed better performance characteristics than the PRIME-MD in identifying
      current cases. The specificity of the PDI-29 was 59.0% and its sensitivity was
      73.6%. These results lead us to the conclusion that the PRIME-MD, previously
      proposed by Spitzer, R.L., Williams, J.B., Kroenke, K., Linzer, M., DeGruy, F.V.
      3rd, Hahn, S.R., et al. (1994, Utility of a new procedure for diagnosing mental
      disorders in primary care. The PRIME-MD 1000 study. Journal of the American
      Medical Association, 272 (22), 1749-1756.) to help physicians in primary care
      clinics, could be less appropriate than the PDI-29 when used by home care nurses
      in identifying undiagnosed mental health disorders in frail older adults living
      at home. Moreover, this study showed that the health care case manager'sa priori
      judgment on the care receiver's mental health status is not sufficient in
      identifying frail elderly mental health services needs. A two-stage screening
      procedure is proposed to help home care nurses.

PMID- 15511739
TI  - Religiosity and the expansion of caregiver stress.
AB  - We present a stress process framework as a model for understanding how
      religiosity may influence the expansion of stress. Survey data from informal
      caregivers to a spouse with Alzheimer's disease or a related dementia (n = 200)
      were analyzed to observe the relationships among three variables: (1) care
      related stress, (2) religiosity, and (3) depression. This sample, which has a
      mean age of 73 years, demonstrates high rates of self-described religiosity,
      church attendance and frequency of prayer. Using these criteria, women and
      racial/ethnic minority caregivers are the most religious. In a series of
      multivariate analyses, we found strong evidence to suggest that there is an
      expansion of care-related stressors leading to depression in this sample.
      Religiosity, as measured here, appears to be largely unrelated to stress and
      stress expansion. We found no evidence to suggest that it moderates stress
      expansion. However, these data do suggest that one stressor--feelings of role
      overload--is correlated with greater levels of self-perceived religiosity, which
      among caregivers who have health problems of their own is associated with greater
      depressive symptomatology. Thus, for a sub-sample of these caregivers, we find
      weak evidence of a mediation effect wherein one subjective, non-organizational
      dimension of religiosity is a conduit of the harmful effects of stress (rather
      than a suppressor). Results and data limitations are discussed in relation to
      better assessing the role of religiosity and spirituality in the experience of
      the stress process.

PMID- 15511740
TI  - Rural practitioners' experiences in dementia diagnosis and treatment.
AB  - When diagnosis of dementia occurs earlier in the disease process, more time is
      available for treatment aimed at maintaining patient function and delaying
      decline, and for family education about the disease and its management. Primary
      care providers often, however, face challenges in making timely diagnoses.
      Nineteen practitioners in mostly rural areas of a mid-western state were
      interviewed about their experiences in diagnosis and treatment, to develop a more
      comprehensive understanding of barriers encountered by providers in non
      metropolitan areas. Participants estimated that the time from symptom onset to
      diagnosis ranged from several months to one year, largely dependant upon family
      recognition. Limitations in access to consultants and limited or non-existent
      community support and education resources were major impediments to diagnosis and
      treatment, respectively. Like their colleagues in more urban communities, denial
      among family members, or families who were absent or uncooperative, created
      additional challenges for providers in making and communicating diagnoses and in
      supporting home-based or institutional care. Conversely, supportive and motivated
      families played a central role in positive patient care experiences. Participants
      agreed that support and education services were important for family caregivers,
      but generally had few resources to offer families, which constrained their
      ability to provide optimal care. Identifying challenges faced by rural
      practitioners is essential to planning appropriate interventions for consultative
      support and educational outreach.

PMID- 15511741
TI  - Life-long intellectual activities mediate the predictive effect of early
      education on cognitive impairment in centenarians: a retrospective study.
AB  - The purpose of this study was to examine the hypothesis of whether early
      education and/or maintaining intellectual activities over the life-course have
      the power to protect against cognitive impairment even in extremely old adults.
      Ninety centenarians from the population-based Heidelberg Centenarian Study were
      assessed with a modified version of the Mini Mental State Exam (MMSE). Data about
      education, occupational status, and life-long intellectual activities in four
      selected domains were obtained. Results demonstrated that 52% of the sample
      showed mild-to-severe cognitive impairment. Analyzing the influence of early
      education, occupational status, and intellectual activities on cognitive status
      we applied several (logistic) regression analyses. Results revealed independent,
      significant and strong influence of both formal school education and intellectual
      activities on the cognitive status in very late life, even after controlling for
      occupational status. However, about one fourth of the effect of early education
      on cognitive status was exerted indirectly via the assessed intellectual
      activities. In summary, the present study provides first evidence for the
      conclusion that even with regard to cognitive performance in very old age, both
      early education and life-long intellectual activities seem to be of importance.

PMID- 15511742
TI  - Associations of caregiver stressors and uplifts with subjective well-being and
      depressive mood: a meta-analytic comparison.
AB  - The present meta-analytic study gives a systematic review of research on
      depression and the subjective well-being of caregivers. We integrate results from
      60 studies on informal caregivers' subjective well-being (e.g., positive affect,
      life-satisfaction) and contrast them with the result of studies on caregiver
      depression. Analyses were based on a two-factor model of subjective well-being
      that distinguishes between positive and negative dimensions of well-being (e.g.,
      happiness and depression). The strongest effects were domain-specific: uplifts of
      caregiving were associated with subjective well-being and caregiving stressors
      were associated with depression. In addition, weaker effects that crossed domains
      were present: uplifts were weakly associated with depressive symptoms. In
      addition, lower levels of caregivers' subjective well-being were weakly related
      to care receivers' physical and cognitive impairments, as well as behaviour
      problems, but not to the amount of caregiving. Type of care recipients' illness
      and the measure of well-being moderated, in part, the association between
      stressors/uplifts and subjective well-being.

PMID- 15511744
TI  - Supported living in residential homes for the elderly: impact on patients and
      elder care workers.
AB  - To enable older people with severe and persistent mental illness to live in the
      community, the Dutch mental health sector has developed a program for supported
      living in residential homes for the elderly. It provides for the permanent
      stationing of mental health workers (MHWs) in elder care facilities to support
      both the resident patients and the elder care staff. The authors examined
      associations between the number of MHW staff and the degree to which (1) patients
      were integrated into the community and (2) elder care workers had developed
      effective working alliances with their patients. Participants included 110
      patients participating in 18 supported living programs in the Netherlands.
      Community integration was assessed in face-to-face interviews with the patients
      about their perceived influence over daily life, involvement in social
      activities, and social network size. The quality of the worker-patient
      relationship was assessed using the Dutch Working Alliance Questionnaire for
      Community Care, completed by the elder care worker primarily responsible for each
      patient. After differentiation of the MHW staff into medically trained and nurse
      trained professionals, associations with outcome measures were found only for the
      nurse-trained staff. The more hours of nurse-trained staff capacity per patient,
      the more influence perceived by the patients, and the more directiveness shown by
      the elder care workers in their contacts with patients. The impact of supported
      living programs in residential homes for the elderly appears to be determined in
      part by the caseloads of the on-site MHWs.

PMID- 15511743
TI  - Measurement of leisure time satisfaction in family caregivers.
AB  - Caregiving is known to limit participation in a variety of roles. Leisure roles
      are increasingly recognized as important for the well-being of older adults.
      Little is known, however, about the impact of caregiving on leisure activities,
      and existing measures are of limited utility in caregiving research. We developed
      the Leisure Time Satisfaction (LTS) measure to allow further study of the impact
      of caregiving on caregivers' leisure time satisfaction, the role of leisure in
      understanding the caregiving process, and whether caregiving interventions
      improve leisure time satisfaction. The six-item LTS measure shows excellent
      psychometric properties, including internal consistency, a single factor
      structure, and convergent validity. Psychometric features are robust across
      diverse groups of caregivers, including subgroups varying by race/ethnicity and
      relationship to the care recipient. The LTS measure appears to be a promising
      tool for inclusion in caregiving research.

PMID- 15511747
TI  - Shifts in the philosophical foundations of psychiatry since Jaspers: implications
      for psychopathology and psychotherapy.
AB  - Jaspers' AllgemeinePsychopathologie, the General Psychopathology, published in
      1923, had a profound influence on the development of psychiatry. Central to it
      was the attempt to give the new psychiatry a philosophical foundation, the key
      element in which was the dichotomy between meaningful and causal connections.
      This dichotomy was superimposed on the earlier mind-body distinction, and both
      converged on the conclusion that mind and meaning were problematic from the point
      of view of science. The inevitable splits came to a head in the 1960's, with
      attacks on the one side by the other: medical psychiatry was attacked for
      systematically stripping madness of its meaning and hence dehumanising it, while
      psychoanalysis, the champion of meaning, was rounded upon for being unscientific.
      At the same time however there was emerging a new paradigm that effectively
      deconstructed the problematic, namely, the cognitive or information-processing
      paradigm. This paradigm has made it possible to construct a unified bio-psycho
      social science of psychopathology. In psychotherapy, the shift has been away from
      the view that meaning is non-causal, a matter only of existential significance or
      of hermeneutic interpretation, towards the working assumption that it is
      crucially involved in aetiology, as in the new cognitive behaviour therapy
      paradigm.

PMID- 15511748
TI  - Merleau-Ponty's body-subject and psychiatry.
AB  - The paper aims to shed philosophical light on the ways in which we can make sense
      of human behaviour, using some aspects of the thoughts of Maurice Merleau-Ponty
      (1908-1961). The concept of 'intentionality' is introduced as a mark of human
      action, and a traditional philosophical distinction between the causal
      explanation of movements and the 'empathetic' understanding of intentional
      actions is examined. It is argued that this distinction creates difficulties for
      the explanation of mental disorder. Merleau-Ponty's concept of the 'body-subject'
      is argued to be a way of overcoming these difficulties, by proposing a form of
      non-eliminativist materialism. Mental disorder is to be seen as a deviant way of
      'being-in-the-world', which can be 'understood', but only with difficulty, and
      where the deviance requires in addition a causal explanation, either in
      neurophysiological terms or in terms of early development. It is concluded that
      this offers a way of combining a humanistic approach to psychiatric disorder with
      full recognition of the role of physical treatments.

PMID- 15511749
TI  - The conceptual framework for the investigation of emotions.
AB  - The experimental study of the emotions as pursued by LeDoux and Damasio is argued
      to be flawed as a consequence of the inadequate conceptual framework inherited
      from the work of William James. This paper clarifies the conceptual structures
      necessary for any discussion of the emotions. Emotions are distinguished from
      appetites and other non-emotional feelings, as well as from agitations and moods.
      Emotional perturbations are distinguished from emotional attitudes and motives.
      The causes of an emotion are differentiated from the objects of an emotion, and
      the objects of an emotion are distinguished into formal and material ones. The
      links between emotions and reasons for the emotion, for associated beliefs and
      for action are explored, as well as the connection between emotion and care or
      concern, and between emotion and fantasy. The behavioural criteria for the
      ascription of an emotion are clarified. In the light of this conceptual network,
      Damasio's theory of the emotions is subjected to critical scrutiny and found
      wanting.

PMID- 15511750
TI  - Doing without deliberation: automatism, automaticity, and moral accountability.
AB  - Actions performed in a state of automatism are not subject to moral evaluation,
      while automatic actions often are. Is the asymmetry between automatistic and
      automatic actions justified? In order to answer this question we need a model of
      moral accountability that does justice to our intuitions about a range of modes
      of agency, both pathological and non-pathological. Our aim in this paper is to
      lay the groundwork for the development of such a model.

PMID- 15511751
TI  - Wittgenstein and the limits of empathic understanding in psychopathology.
AB  - The aim of this paper is three-fold. Firstly, to briefly set out how strategic
      choices made about theorising about intentionality or content have actions at a
      distance for accounting for delusion. Secondly, to investigate how successfully a
      general difficulty facing a broadly interpretative approach to delusions might be
      eased by the application of any of three Wittgensteinian interpretative tools.
      Thirdly, to draw a general moral about how the later Wittgenstein gives more
      reason to be pessimistic than optimistic about the prospects of a philosophical
      psychopathology aimed at empathic understanding of delusions.

PMID- 15511752
TI  - Understanding the clinical concept of delusion: from an estranged to an engaged
      epistemology.
AB  - Delusion is relatively easy to diagnose but near impossible to define. This paper
      (I) uses the method of 'philosophical fieldwork' to show that standard approaches
      use definitions that are both over- and under-inclusive. It argues furthermore
      that such approaches typically presuppose what is here dubbed an 'estranged'
      epistemology. This epistemology supposes that our understanding of the world
      occurs outside of, and consequent on, our experience of it. Instead of this an
      alternative 'engaged' epistemology is set out. This alternative sees experience
      itself as the vehicle of our most fundamental comprehending engagement with the
      world. (II) This, it is argued, makes better sense both of our contact with
      reality and of the failure of this contact in delusion. (III) The implications of
      this alternative theorisation for the cognitive psychology of delusion are
      discussed.

PMID- 15511754
TI  - Review of Propess--a controlled release dinoprostone (prostaglandin E2 ) pessary.

PMID- 15511753
TI  - Reconceiving delusion.
AB  - Delusions are critical components in a number of mental disorders, schizophrenia
      foremost. What are they? The standard view is that they are a type of belief--a
      pathological belief. Unfortunately, the standard view does not consistently
      correspond to clinical practice, where the term 'delusion' often applies to non
      beliefs. We review the case for saying that non-beliefs can count as delusions.
      We argue that delusions are complexes of higher and lower order attitudes. They
      constitute a distinctive type of failure of self-knowledge and self-management.
      We describe the relevant type. One of the conceptual implications of our view is
      that beliefs need not be central to delusions.

PMID- 15511755
TI  - Lichen sclerosus.
AB  - Lichen sclerosus is commonly seen in middle-aged and elderly women but it affects
      both sexes, can occur at any age and anywhere on the body and has been reported
      in most races. Its aetiology is uncertain but there is an increased incidence of
      auto-immune antibodies in lichen sclerosus and an association with auto-immune
      disease such as vitiligo, thyroid disease and alopecia areata. Lichen sclerosus
      has been observed in different generations of a family but no consistent genetic
      pattern has emerged. Lichen sclerosus typically affects the anogenital region and
      presents with an intractable 'burning' pruritus. Extragenital lesions do not
      itch. Oral lesions occur in lichen sclerosus and may resemble lichen planus.
      Lichen sclerosus exhibits the isomorphic or Koebner phenomenon. The literature
      supports the view that lichen sclerosus is not a precancerous lesion but there is
      a significant association with vulval squamous cell carcinoma. Patients with
      inactive, treated lichen sclerosus should be reviewed annually. The treatment of
      choice of uncomplicated genital lichen sclerosus is a topical steroid of a potent
      or super-potent category. In males, circumcision may be indicated if topical
      measures are unsuccessful. In women, surgery is considered predominantly for
      cancer confirmed by tissue examination.

PMID- 15511756
TI  - The efficacy of phenytoin in eclampsia.
AB  - Although the Eclampsia Trial Collaborative Group reported that magnesium sulphate
      was more effective in preventing recurrent convulsions in eclampsia than
      phenytoin, confirmatory evidence that phenytoin is not useful as a prophylactic
      anticonvulsant agent in eclampsia is necessary. This prospective descriptive
      study enrolled 68 women with eclampsia. Recurrence of seizures occurred in 18
      (26.5%) patients following phenytoin therapy. In 16 patients, the seizure
      recurrence occurred between the loading dose and first maintenance dose at 6
      hours. There was no statistical difference in the clinical characteristics of
      those who had seizure recurrence compared with those that did not. Seizure
      recurrence following phenytoin therapy in eclampsia is unacceptably high. These
      results suggest that phenytoin is not effective as a prophylactic anticonvulsant
      in eclampsia. No conclusions about its effectiveness compared with alternative
      prophylactic anticonvulsants can be made from this descriptive study.

PMID- 15511757
TI  - Predictive value of amniotic fluid and fetal blood cultures in pregnancy outcome
      in preterm prelabour rupture of membranes.
AB  - We carried out a comprehensive prospective study of 26 pregnancies complicated by
      preterm rupture of the membranes. Microbiological assessment included cultures
      for aerobic and anaerobic bacteria, Mycoplasmas, Chlamydia, Trichomonas and fungi
      from: high vaginal and cervical swabs, maternal blood and urine, amniotic fluid
      and fetal blood on admission and finally, placenta and umbilical cord = after
      delivery. The group with positive cultures (n 16), was compared with the group
      with negative cultures = (n 10) in terms of gestational age at labour, latent
      phase after membrane rupture and fetal and neonatal morbidity and mortality. All
      patients with positive cultures delivered before 32 weeks and their neonates had
      evidence of infection. Three intrauterine deaths occurred in this group and 12/13
      (86%) of the live neonates were admitted to the neonatal intensive care unit. The
      10 (38%) patients of the group with negative cultures delivered after 32 weeks,
      had no perinatal deaths, and only two were admitted to neonatal intensive care.
      The median latent phase differed between these two groups (4.5 vs. 53.5 days, P
      0.01), as did the median gestational age at labour (28 vs. 36 4 weeks, P 0.01). A
      positive amniotic fluid or fetal blood culture in the clinical setting of preterm
      rupture of the membranes indicates labour onset within a few days. Intrauterine
      infection with fetal sepsis is accompanied by high neonatal infectious morbidity
      (100%) and mortality (30%).

PMID- 15511758
TI  - Congenital anomalies among infants of diabetic mothers: a study of 466 cases at
      King Fahd Hospital of the University, Al-Khobar.
AB  - The purpose of the study was to determine the incidence of congenital anomalies
      among infants of diabetic mothers and compare this with the normal obstetric
      population in our hospital. Among 17 463 patients delivered at the King Fahd
      Hospital of the University, Al-Khobar, Saudi Arabia between January 1987 and
      December 1992 there were 466 diabetic mothers who delivered 466 singleton births.
      The incidence of diabetes was 2.6%. Among those 466 diabetic patients there were
      132 with clinical diabetes which was present before pregnancy and which required
      insulin treatment during pregnancy and 334 with gestational diabetes. There were
      14 lethal congenital anomalies among the infants of diabetic mothers (3%)
      compared with 69 anomalies in general obstetric population (0.4%). The difference
      = was very highly significant P = 0.001. Ten anomalies were responsible for 10
      stillbirths and the other four anomalies resulted in four neonatal deaths. The
      most common anomalies were those of the central nervous system and multiple fetal
      anomalies, followed by cardiovascular system, renal and chromosomal anomalies.
      All those anomalies occurred in the infants whose mothers had clinical diabetes.

PMID- 15511759
TI  - 'Near-miss' obstetric enquiry.
AB  - A near-miss maternal mortality enquiry was performed at University College
      Obstetric Hospital, London, by reviewing retrospectively all 30 obstetric
      admissions to the intensive care unit (ITU) over a two-year period. The obstetric
      admission rate to ITU was 0.5 (95% CI 0.32-0.67%), or one per 200 women
      delivered. Haemorrhage and severe pre-eclampsia were the two commonest causes of
      admission. Sub-standard care was identified in 52% of cases. Blood loss was often
      massive ( 2000 ml), underestimated and required large volume transfusions (mean
      transfusion 6.4 units, range 1-24). Although there are problems with definitions,
      ascertainment and validity, 'near-miss' review is feasible. It is worthwhile for
      every hospital to carry out its own 'near-miss' enquiry using appropriate local
      criteria to identify potential areas for improvements. 'Near-misses' are more
      prevalent than deaths and are dominated by conditions that are amenable to
      treatment. They may be even more sensitive to improvement or deterioration in
      obstetric services than mortality data.

PMID- 15511760
TI  - A randomised placebo controlled trial of loop diuretics in moderate/severe pre
      eclampsia, following delivery.
AB  - Nineteen patients with pre-eclampsia were randomised to receive 40 mg of
      frusemide or placebo by mouth daily for 7 days in the first post-partum week.
      Outcome measures included mean and maximum blood pressure, the need for
      additional antihypertensive treatment during that period and mean length of
      hospital stay. There were no statistically significant differences in outcome
      between the treatment and placebo groups although there was a trend to more rapid
      lowering of blood pressure following delivery in those receiving frusemide.

PMID- 15511761
TI  - The prediction of pregnancy outcome by haemoglobin measurement before 20 weeks'
      gestation.
AB  - Maternal haemoglobin levels were measured before 21 weeks' gestation in a
      prospective study of 1276 singleton pregnancies. Reference ranges were
      constructed and then applied to a further cohort of 1227 singleton pregnancies to
      determine the ability of haemoglobin level before 21 weeks' gestation to predict
      pregnancy outcome. Haemoglobin level decreased significantly with advancing
      gestational age from 6 to 21 weeks (P < 0.05). Low haemoglobin level was
      associated with a decreased risk of pregnancy-induced hypertension (adjusted odds
      ratio 0.51, 95% CI 0.35-0.74). High haemoglobin level was positively correlated
      with subsequent pregnancy-induced hypertension (P = 0.002) with values > 95th
      percentile for gestational age having positive and negative predictive values of
      33% and 94% respectively. Haemoglobin values (either high or low) were not
      predictive of proteinuric pre-eclampsia, preterm prelabour rupture of the
      membranes, preterm birth, low birth weight or the need for neonatal resuscitation
      of admission to the special care baby unit. The finding of a high maternal
      haemoglobin before 21 weeks' gestation is not sufficiently predictive of
      pregnancyinduced hypertension to be of clinical use, but the ability of a low
      level to predict favourable outcome may be of use in a scoring system designed to
      identify women suitable for midwifery-based care.

PMID- 15511762
TI  - The prophylactic use of diclofenac (Voltarol) suppositories in perineal pain
      after episiotomy. A random allocation double-blind study.
AB  - One hundred and ten patients who had episiotomies to aid normal vaginal delivery
      without epidural analgesia were = allocated at random to receive either
      diclofenac (n = 56) or = placebo (n = 54) suppositories. Pain after episiotomy
      was assessed at 24 and 48 hours using a combination of a visual analogue scale, a
      modified pain score and a review of additional analgesia required. All patients
      in both groups were allowed routine hospital analgesia on request. Our data
      suggests that very few patients suffered severe pain, even in the placebo group.
      However, the prophylactic use of diclofenac suppositories significantly reduced
      perineal pain in the first 24 hours, although the difference was less marked by
      48 hours. Overall additional analgesia requirement was correspondingly less in
      the diclofenac group.

PMID- 15511763
TI  - Multiple births in Nigerian Igbo women: incidence and outcomes.
AB  - The rate of multiple births varies amongst races and ethnic groups. This study
      shows that the incidence of multiple births among the Nigerian Igbo women is one
      in 35.5 or 28.2 per 1000 births. A significant difference in Apgar scores at 1
      minute between the first and second twins suggests a greater risk for the second
      twin following the delivery of the first twin. Significantly lower Apgar scores
      and higher perinatal mortality rate in the twins compared with the singleton
      controls also indicate greater hazard for the multiple births in general.
      Successful management of multiple pregnancy can occur following early diagnosis
      and confirmation of fetal presentations, adequate antepartum fetal surveillance
      and prompt management of pregnancy complications; appropriate referrals to
      specialised centres when indicated; and prompt decisions as to timing and mode of
      delivery.

PMID- 15511764
TI  - The management of cervical incompetence with protruded membranes into the vagina
      by vaginal irrigation with granulocyte elastase inhibitor: ulinastatin and PVP
      iodine solution.
AB  - In an attempt to prevent preterm premature rupture of the membranes (PPROM) and
      to prolong the duration of pregnancy in patients with a dilated cervix and with
      the membranes protruding into the vagina, the combination therapy of irrigation
      with a solution containing granulocyte elastase inhibitor (ulinastatin) and PVP
      iodine onto the membranes, as well as the use of antibiotics and tocolytic
      agents, was tested. Ten patients with protruding membranes were treated by this
      combination therapy and five patients were instructed to have strict bedrest
      without any medication. In the non-treated group, all patients were delivered
      within 2 days of admission and all babies had a poor prognosis. In the treated
      group, the pregnancy was prolonged by between 3 and 108 days (mean values 33.6
      days). Only two out of 10 patients had PPROM. In cases with protruding membranes,
      this combination therapy seemed to be useful in preventing rupture and so
      prolonging the pregnancy and increasing the survival rate of the infants.

PMID- 15511765
TI  - Emergency cervical circlage for cervical incompetence.
AB  - Twelve patients had emergency cervical circlage for inevitable middle trimester
      abortion due to cervical incompetence. The mean gestation was 23 weeks (range 15
      28 weeks). The median cervical dilatation was 3 cm. In three patients, the
      cervical dilatation was more than 5 cm. The median prolongation of pregnancy was
      3.3 weeks (range 4 days to 10 weeks). Eight of the 14 babies survived. All babies
      that survived were more than 1000 g. Based on our experience, we advocate an
      active approach to inevitable middle trimester abortions due to cervical
      incompetence.

PMID- 15511766
TI  - Twinning in women under the age of 20 years.
AB  - A review of twin pregnancies in women under 20 years of age at conception showed
      a ratio of dizygotic twins to monozygotic twins of 3:2. This is at variance with
      the ratio previously noted in other age groups.

PMID- 15511767
TI  - Three successive pregnancies in a patient with Takayasu's arteritis.
AB  - Takayasu's arteritis is a rare non-specific obliterative panarteritis of unknown
      origin that occurs predominantly in young Asian and Oriental females of
      childbearing age and has been encountered in the UK. With the exception of a few
      large series from the Far East, much of the information on Takayasu's arteritis
      in pregnancy comes from isolated case reports with no long term follow-up after
      pregnancy. We report a patient with this condition who had three pregnancies
      during a 4-year follow-up period with no serious complications.

PMID- 15511768
TI  - Placental abruption following induction of labour with prostaglandin gel.

PMID- 15511769
TI  - Massive secondary postpartum haemorrhage from rupture of thrombosed uterine
      artery following lower segment caesarean section.

PMID- 15511770
TI  - First trimester traumatic tetraplegia-management of pregnancy and delivery.

PMID- 15511771
TI  - Generalised convulsion as the first clinical sign of a brain tumour during
      pregnancy.

PMID- 15511772
TI  - Combined intrauterine and abdominal pregnancy.

PMID- 15511773
TI  - Diabetes insipidus, a rare complication of HELLP syndrome. Report of local
      experience and review of the literature.

PMID- 15511774
TI  - May-Hegglin anomaly in pregnancy.

PMID- 15511775
TI  - Obstetric fistulae: a retrospective study of 1210 cases at the Addis Ababa
      Fistula Hospital.
AB  - The results of surgery in new patients presenting with a vesico-vaginal fistula
      are presented to relate the outcome to age, parity and aetiology of the fistula.
      Of the 1435 patients admitted to the hospital from January 1991 to December 1992,
      1210 had had no previous attempt to repair the fistula and are included in the
      study. The data were collected from the patients records and a specially designed
      admission and treatment form. Of the 1210 cases analysed, the fistula was caused
      by obstructed labour in 96% (1160), and in the majority of these, labour was
      obstructed for more than 3 days. Half of the patients (598) were aged between 13
      and 20 years on admission to hospital. Fifty-five per cent (649) developed a
      fistula during their first delivery and in 93% the fetal outcome was a still
      birth. Of the operated 1210 cases, 1120 (92.6%) were successfully repaired. Five
      hundred and thirty patients were divorced by their husbands following development
      of the fistula. Illiteracy as common among the patients. Improvements in
      maternity services, development of communication networks and eradication of
      illiteracy are essential for the prevention of obstetric fistula. The role of
      reconstructive vaginal fistula surgery and the further training in this field is
      also emphasised.

PMID- 15511776
TI  - Hysterectomy following failed endometrial resection.
AB  - Of the first 500 women in Oxford to undergo transcervical resection of the
      endometrium, 101 (20%) have subsequently undergone hysterectomy. This study was
      undertaken to assess the reasons for failure of endometrial resection. An audit
      of the case notes of the 101 women requiring hysterectomy was performed. Data
      collection included the patient's age, weight, parity, reasons for endometrial
      resection, details of the endometrial resection, reasons for hysterectomy,
      hysterectomy findings and uterine histology. Six (6%) hysterectomies were
      performed as emergency operations during endometrial resection, 33 (33%) were
      performed for persistent menorrhagia, 39 (39%) for recurrent menorrhagia and in
      18 women (18%) for pelvic pain. The duration of success following endometrial
      resection ranged from 0 to 21 months. Hysterectomy was significantly more common
      in older women under 40 years of age, in the presence of an enlarged fibroid
      uterus, when complications at endometrial resection had occurred and in women
      operated on by relatively inexperienced surgeons. Endometrium ws present in 96%
      of hysterectomy specimens. Uterine malignancy that had not been diagnosed at
      transcervical resection of the endometrium was present at hysterectomy in two
      women. Hysterectomy should be considered in preference to endometrial resection
      for treatment of menorrhagia in women who are less than 40 years old and in the
      presence of large intramural fibroids.

PMID- 15511777
TI  - Preliminary trial of photic stimulation for premenstrual syndrome.
AB  - In an open study 17 women with confirmed, severe and long-standing premenstrual
      syndrome used photic stimulation with a flickering red light, every day for up to
      four menstrual cycles. At the end of treatment prospectively recorded median
      luteal symptom scores were reduced by 76% (95% confidence interval 54-93, P <
      0.001), with clinically and statistically significant reductions for depression,
      anxiety, affective lability, irritability, poor concentration, fatigue, food
      cravings, bloating and breast pain. Twelve of the 17 patients (71%) no longer had
      the premenstrual syndrome. One patient failed to improve. One patient withdrew
      because of worsening premenstrual depression, but photic stimulation was
      otherwise well tolerated. The improvement is greater than that reported for
      relaxation or in open studies of fluoxetine, and much more than historical
      placebo rates. Photic stimulation may be a useful treatment for the premenstrual
      syndrome, and by its suggested action on circadian rhythms may have wider
      therapeutic applications.

PMID- 15511778
TI  - Types of ovarian tumours seen in Benin-City, Nigeria.
AB  - There were 243 histologically proven ovarian tumours seen at the University of
      Benin Teaching Hospital, Benin-City, from 1973 to 1987. Out of these 198 (81%)
      were benign, with dermoid cyst (31%) being the commonest benign ovarian tumour.
      Granulosa cell tumours was the commonest malignant ovarian tumour seen (20% of
      malignant cases).

PMID- 15511779
TI  - A prospective study of the correlation between genital pathogens and morbidity
      following diathermy loop excision of the transformation zone.
AB  - A prospective study of 48 women was carried out to estimate the incidence of
      common genital pathogens in women referred to colposcopy clinic requiring
      diathermy loop excision and to compare patient morbidity in the subgroups with
      and without genital pathogens. Of the 43 women included in the analysis, genital
      pathogens were present in 24 cases (56%) and absent in 19 (44%) of the 24
      positive cases, 19 (79%) women had pathogen(s) on the cervical swab, 24 (100%)
      had pathogen(s) on the high vaginal swab and 15 (63%) had both a positive
      cervical and high vaginal swab (HVS). The most frequently isolated groups of
      organisms were mixed anaerobes, alone (four HVS and four cervical) or in
      combination with Gardnerella vaginalis (four HVS and three cervical) or coliforms
      (two HVS and two cervical). The mean duration of bleeding and vaginal discharge
      in the two study groups was not statistically significant (t value 1.97, P 0.05;
      and t value 0.48, P 0.5, respectively). However, the mean duration of bleeding
      graded by the patient as being moderate to severe was significantly different in
      the two groups (t value 3.18 P 0.01). Fifty-six per cent of the women in the
      study had confirmed genital pathogens, predominantly anaerobes, and the prolonged
      moderate-to-severe bleeding in this group suggests a potential role for
      prophylactic bacteriocides, although the study size was unable to implicate a
      single pathogen.

PMID- 15511780
TI  - Dual detection of human herpesvirus-6 and human papillomavirus type 16 and 18 in
      cervical carcinoma.
AB  - Introduction It is widely accepted that certain 'high risk' human papillomavirus
      (HPV) genotypes, particularly HPV 16 and 18 are aetiological agents in the
      development of neoplasia of the uterine cervix. The long latent period between
      initial HPV infection and emergence of carcinoma suggests that HPV alone is
      insufficient for malignant transformation and additional factors are required for
      the progression of HPV infected cells to a neoplastic phenotype. Cells with
      integrated HPV express viral E6 and E7 oncoproteins which are crucial for
      immortalisation of epithelial cells via their action on host p53 protein. It is
      therefore of particular interest to elucidate the molecular mechanisms that alter
      the expression of E6/E7 proteins during HPV-associated tumorigenesis. Recently,
      human herpesvirus-6 (HHV-6) has been shown to infect a HPV-immortalised cervical
      epithelial cell line and transactivate HPV 18 promoters, upregulating gene
      expression of E6 and E7 HPV oncoproteins (Chen et al., 1994; DiPaolo et al.,
      1994). HHV-6, first isolated from peripheral blood mononuclear cells of patients
      with AIDS and lymphoproliferative disorders, is the causative agent of exanthem
      subitum, heterophile-negative infectious mononucleosis and other febrile
      illnesses. HHV-6 has recently been detected in oral carcinomas (Yadav et al.,
      1994). HHV-6 also contains DNA sequences which can transform epithelial cells in
      culture.

PMID- 15511781
TI  - Giant myometrial cyst.

PMID- 15511782
TI  - Gardnerella vaginalis causing tubo-ovarian abscess.

PMID- 15511783
TI  - Isolated vulval oedema as a feature of Crohn's disease.

PMID- 15511784
TI  - Uterus-like mass of the ovary.

PMID- 15511785
TI  - Pure epidermoid cysts of the ovary.

PMID- 15511786
TI  - Two different types of human papillomavirus in a patient with carcinomas of the
      vulva and cervix.

PMID- 15511787
TI  - Neuroendocrine (Merkel cell) carcinoma of the vulva.

PMID- 15511788
TI  - Ataxia as a presentation of ovarian carcinoma.

PMID- 15511789
TI  - Reconstructive surgery in advanced cervical cancer.

PMID- 15511790
TI  - Large vaginal leiomyomas excised by abdomino-vaginal approach.

PMID- 15511791
TI  - Uterine vein thrombosis: an unusual variant of pelvic vein thrombophlebitis.

PMID- 15511792
TI  - Use of mifepristone in second trimester termination of pregnancy in a patient
      with anomalous reproductive tract anatomy.

PMID- 15511793
TI  - Atypical polypoid adenomyoma of the uterus.

PMID- 15511794
TI  - Laparoscopic management of ectopic pregnancies.

PMID- 15511796
TI  - Gynaecological tuberculosis since 1951.
AB  - A study has been made of 711 patients with proved gynaecological tuberculosis
      investigated between 1 January 1951 and 31 December 1994. The main presenting
      symptoms in order of frequency were infertility, pelvic pain, excessive menstrual
      loss and amenorrhoea. The average age at first attendance was 31 years, only 16%
      of married women had been pregnant and palpable adnexal masses were found in 47%.
      Eight drug programmes were used, the best results being obtained with
      streptomycin, para-aminosalicyclic (PAS) acid and isoniazid or with rifampicin,
      ethambutol and isoniazid. Toxic drug reactions occurred in 114 patients, the
      drugs responsible in the majority being streptomycin and PAS. Where drug
      treatment failed, surgery under further drug cover was employed in 85 patients,
      with no deaths and no fistulae. After treatment, there were 95 pregnancies in 57
      patients. In recent years there has been a rise in the incidence of tuberculosis
      in general in the Western world. Many factors play a part in this, by far the
      most important being the spread of AIDS.

PMID- 15511797
TI  - Fetal magnetoencephalographic mapping in normal and pre-eclamptic pregnancies.
AB  - This study investigates the fetal brain activity in normal and pre-eclamptic
      pregnancies. Measurements were performed by means of a superconducting quantum
      interference device (SQUID) in an electrically shielded room of low magnetic
      noise. The study was prospective. Ten pregnant women with pre-eclampsia and 11
      healthy gravidae were included. All were preterm at 28 to 37 weeks' gestation.
      Biomagnetic signals (waveforms), recorded from the fetal brains in the
      frequencies 2-7 Hz, were expressed in terms of magnetic power spectral
      amplitudes: these were low in almost all normal pregnancies, and high in most
      pregnancies complicated with pre-eclampsia. The pictorial representation of the
      results in the form of iso-spectral amplitude (ISO-SA) mapping showed two
      different patterns: (a) iso-contour lines 'organised' in dense concentration
      zones (pre-eclamptic pattern), (b) iso-contour lines at random distribution
      without dense concentration zones (normal pattern). Biomagnetic measurements of
      fetal brain activity is a promising screening procedure for assessing the
      cerebral function, especially at high risk pregnancies.

PMID- 15511798
TI  - Establishing an external cephalic version clinic: outcome of the first year.
AB  - The effect of introducing an external cephalic version (ECV) clinic was evaluated
      after 12 months. The practical procedure of establishing the clinic, its protocol
      and the technique of ECV is described. All women had singleton pregnancies of at
      least 36 weeks gestation. There were 61 'primary' attempts at ECV, and one repeat
      attempt. The operator performing the majority of the ECVs had a 56% success rate,
      whilst the overall rate for the clinic was 53%. There was minimal fetal and
      maternal morbidity. Success according to placental site, parity, gestation and
      type of breech as well as the mode of delivery and neonatal outcome of all
      patients on whom ECV was attempted is presented. There was a significant decrease
      in the total number of breech deliveries, mainly through a 60% reduction in
      emergency caesarean section. The cost effectiveness of the clinic and the use of
      tocolytics is discussed.

PMID- 15511799
TI  - Lipid peroxidation in eclampsia.
AB  - In order to investigate the extent of lipid peroxidation in hypertensive
      disorders of pregnancy, a case-control study was designed. Eight eclamptic women
      were matched with women with severe pre-eclampsia (n = 8) and healthy pregnant
      controls (n = 8). Lipid peroxidation was measured by the malondialdehyde
      thiobarbituric acid reactive assay (MDA-TBAR) and expressed as nmol/ml. Both
      severe pre-eclampsia and eclampsia groups had significantly higher MDA-TBAR
      levels than healthy pregnant women. Eclamptic women before delivery had highest
      MDA-TBAR levels which decreased after delivery.

PMID- 15511800
TI  - Reflex decalcifying algodystrophy of the hip in pregnancy (so-called transient
      osteoporosis). Review of the literature and four case reports.
AB  - Transient algodystrophy of the hip in pregnancy is a relatively rare condition,
      still unknown to many and easily overlooked. Diagnosis is important because of
      the related difficulties in natural delivery and the risk of fracture. Four
      unilateral cases are presented (two right and two left), characterised by pain,
      limping, limitation of the hip motion and demineralisation of the head and neck
      of the femur. Treatment was by rest and protected weight-bearing. Three were
      delivered by caesarean section. In one patient a fracture of the neck of the
      femur occurred a few weeks before delivery, requiring surgery. In all four cases
      the outcome was benign. Like algodystrophy occurring in adults of either sex the
      aetiology is unknown. In pregnant women the association with the right occiput
      anterior position of the fetus (documented in one patient where the affected hip
      was the right) suggests the possible involvement of one of the autonomic pelvic
      plexuses (right or left) in the unilateral cases.

PMID- 15511801
TI  - Vaginal delivery after one caesarean section in Nigerian women.
AB  - A total of 120 Nigerian women at term pregnancy with one previous caesarean
      delivery were studied between June 1988 and May 1993. Elective caesarean section
      was performed in 3 (2.5%). Vaginal delivery was achieved in 101 (86.5%) of those
      allowed a trial of labour. Intrapartum caesarean section was done in 16 (13.7%)
      cases. Rupture of the uterus occurred in 3 cases (2.6%) with perinatal loss of 2
      babies. There was no maternal mortality. There was no significant correlation
      between vaginal delivery and birth weight, gestational age or initial indication
      for the primary caesarean section. It is concluded that trial of labour is safe
      after a previous caesarean section in selected patients.

PMID- 15511802
TI  - The effect of a depressed economy on the utilisation of maternal health services:
      the Nigerian experience II.
AB  - This study follows an earlier one on the effect of the depressed Nigerian economy
      on the utilisation of maternal health services. Since then, there has been an
      observed and continued deterioration in maternal health service utilisation. The
      present study compares service utilisation within three time periods: pre
      Structural Adjustment Programme (SAP) period of 1980-84; 1985-89 and 1990-94,
      revealing a continued decline in antenatal bookings, obstetric admissions and
      hospital deliveries with figures well below the pre-SAP levels. Maternal and
      perinatal morbidity have maintained a disproportionate upward trend.
      Specifically, perinatal mortality, obstructed labour and anaemia increased by two
      , three- and six-fold respectively in the decade between the pre-SAP period and
      1990-94 time period. Maternal mortality ratio of 9.3 per 1000 births is a 1.5
      increase over pre-SAP level. The findings indicate a continuation over unsafe
      reproductive life among Nigerian women with bleak prospects into the 21st century
      and call for urgent change in government policy.

PMID- 15511803
TI  - The effects of smoking on labour after uncomplicated pregnancy: a comparison
      between the progress and outcome of labour in 400 smokers and 400 matched non
      smokers.
AB  - A comparison was made between the progress of labour and its outcome after an
      uncomplicated pregnancy, in 400 smokers and 400 non-smokers. Strict selection
      criteria were applied to eliminate, as far as possible, the variables which might
      have influenced labour in both groups and to ensure that the two groups of women
      were matched. The duration of labour was longer in smokers, who also had a higher
      incidence of caesarean sections. Smokers had a higher incidence of retained
      placenta and postpartum haemorrhage. The neonates of smokers had a higher
      incidence of problems in the immediate post-delivery period.

PMID- 15511805
TI  - Antenatal care and delivery of a patient with spinal muscular atrophy complicated
      with severe.

PMID- 15511804
TI  - Hereditary angioneurotic oedema in pregnancy coincidentally associated with
      herpes gestationis.

PMID- 15511806
TI  - Cortical blindness due to pregnancy-induced hypertension in the presence of a
      normal magnetic.

PMID- 15511807
TI  - Long-term follow up after a severe haemorrhage within a prolactin-producing
      pituitary adenoma.

PMID- 15511808
TI  - Caecal volvulus and malrotation of the bowel complicating the third trimester of
      pregnancy.

PMID- 15511809
TI  - Placenta percreta presenting as a uterine tumour and persistent vaginal bleeding
      in the first.

PMID- 15511810
TI  - Neuroleptic malignant syndrome in hyperemesis gravidarum.

PMID- 15511811
TI  - Breastfeeding and placental abruption.

PMID- 15511812
TI  - Varicella pneumonia complicating pregnancy.

PMID- 15511813
TI  - High dose low-molecular-weight heparin (enoxaparin) for the treatment of
      recurrent thromboembolism in pregnancy.

PMID- 15511814
TI  - Therapeutic amniodrainage in chorioangioma.

PMID- 15511815
TI  - Bacterial vaginosis and lower genital tract infections in women attending out
      patient clinics at a tertiary institution serving a developing community.
AB  - The prevalence of bacterial vaginosis and other lower genital tract infections
      were determined in women from a developing community. Patients were recruited
      from four out-patient clinics of a large urban tertiary referral hospital serving
      the indigent Black population of KwaZulu/Natal, South Africa. A total of 208
      women attending the sexually transmitted diseases (STD) (n = 51), colposcopy (n
      =50), family planning (n = 52) and antenatal (n = 55) clinics were investigated.
      Endocervical and vaginal specimens were collected for microbiological
      investigation of recognised sexually transmitted pathogens. Estimation of vaginal
      pH, amine test and wet smear microscopy were performed at the bedside. Peripheral
      venous blood was obtained for serological tests for syphilis, hepatitis B surface
      antigen and antibody to the human immunodeficiency virus (HIV). Vaginal
      infections were detected in a total of 50% (104) of women, endocervical
      infections alone in 9% (18) and concurrent vagino-endocervical infections in 20%
      (41). Bacterial vaginosis (BV) was diagnosed in 35% (73) and its prevalence
      amongst different clinic populations ranged from 25% to 41% with no significant
      differences between any groups. Trichomoniasis was detected significantly more
      often in women attending the STD and antenatal clinics. Endocervical infections
      were found mainly in women attending the STD clinic, though the prevalence of
      Chlamydia trachomatis amongst the other clinic attenders ranged from 13% to 20%.
      Micro-organisms such as Gardnerella vaginalis, Mycoplasma hominis, anaerobes and
      curved Gram-negative rods were found in significantly higher number of women with
      BV. This study confirms the high prevalence of vaginal, endocervical and mixed
      vagino-endocervical infections in women from developing communities. The high
      prevalence of bacterial vaginosis as a single infection and its association with
      other recognised sexually transmitted pathogens in a large proportion of women,
      is of significance since such infections not only predispose to ascending upper
      genital tract infections but are also associated with complications in pregnancy
      such as premature rupture of membranes, preterm labour and endometritis.

PMID- 15511816
TI  - Semiquantitative analysis of human papillomavirus DNA in cervical intraepithelial
      neoplasia by a differential polymerase chain reaction.
AB  - A differential polymerase chain reaction (PCR), which takes account of both the
      human papillomavirus (HPV) type and the amount of viral DNA, was applied to 100
      cervical intraepithelial neoplasias (CIN) in order to improve the
      characterisation of the lesions. One hundred women with cytological smears
      suggestive of CIN I-III and a colposcopically guided punch biopsy were studied.
      DNA was phenol-extracted and a consensus PCR with L1 primers and a type-specific
      PCR for HPV-16 and-18 E6 were performed in parallel. The different sensitivity of
      the PCR methods allowed a semiquantitative analysis of viral DNA. HPV analysis
      was possible in all 100 very small cervical punch biopsies. Of the lesions 79%
      were HPVpositive. The percentage of HPV-16-positive lesions increased
      significantly (P < 0.001) with the degree of severity of CIN (CIN I: 46%, CIN II:
      63%, CIN III: 85%). The percentage of CIN with a high viral load increased also
      with the grade of CIN (CIN I: 8%, CIN II: 33%, CIN III: 44%). Cytologically
      positive lesions (Pap IIID or IVa) had significantly more frequently (p < 0.02) a
      high viral load: 39% vs. 10% of cytologically false negative lesions. In
      conclusion, type-specific PCR had a very high sensitivity in the detection of HPV
      DNA also in cytologically false negative CIN. The addition of the less sensitive
      consensusPCR allowed a semiquantitative analysis of the viral copy number. The
      higher amount of viral DNA in cytologically positive lesions, which may
      correspond to a higher rate of proliferation, reflects a possible role of the
      viral load in the progression of CIN. In clinical practice, differential HPVPCR
      could help to improve the management of CIN.

PMID- 15511817
TI  - Reversal of sterilisation vs. IVF: a cost-benefit analysis.
AB  - A consecutive series of 132 cases of reversal of sterilisation carried out in a
      teaching hospital in England between 1982 and 1995 was analysed. Follow-up data
      was obtained on 112 patients. The overall cumulative conception rate was 47% at
      12 months and 55% at 24 months. Among the 71 pregnancies there were seven
      miscarriages (9%) and 11 ectopic pregnancies (15%). Factors affecting the outcome
      of surgery were examined. The pregnancy rate achieved with microsurgical
      techniques was significantly higher than the conventional (macrosurgical)
      techniques (61% v. 40%, P = 0.05). The method of sterilisation also has a
      significant impact on the outcome; Filshie clips 69%; Fallope ring 46%; Pomeroy
      technique 31% (P < 0.05). Age, associated infertility factors and the interval
      between sterilisation and reversal operation did not appear to have a significant
      impact on the outcome. When compared with IVF, reversal of sterilisation is
      associated with a higher ectopic rate, lower multiple pregnancy rate and a lower
      miscarriage rate. We conclude that reversal of sterilisation carries a higher
      overall success rate than IVF and is more cost effective when the method of
      sterilisation is by the clip or ring and when the reversal operation is carried
      out with microsurgical techniques.

PMID- 15511818
TI  - Laparoscopic assisted vaginal hysterectomy in obese women.
AB  - Twenty-two consecutive patients weighing 100 kg or more and requiring
      hysterectomy were treated by laparoscopic assisted vaginal hysterectomy. The mean
      patient weight was 105.2 kg. In 21 patients, the indication for hysterectomy was
      menorrhagia (9 of these had uterine fibroids) and one patient had microinvasive
      carcinoma of the cervix. Mean operating time was 1 hr. 53 mins; and mean hospital
      stay was 4.5 days. One patient (4.5%) had intraoperative injury to the interior
      epigastric vessels. One patient who had anterior colporrhaphy at the same time
      suffered transient urinary retention which resolved after one week. There were no
      major or long term complications. Our experience suggests that laparoscopic
      assisted vaginal hysterectomy is a feasible and safe option in obese patients.
      The low complication rate may be due, in part, to improved access through the use
      of this approach.

PMID- 15511819
TI  - Are follicle stimulating hormone measurements predictive of ovarian response to
      hyperstimulation with human menopausal gonadotrophin?
AB  - Previous studies have suggested that elevated serum follicle stimulating hormone
      (FSH) concentrations are associated with a poor ovarian response to
      hyperstimulation with human menopausal gonadotrophin (HMG) in in vitro
      fertilisation (IVF) programmes. We have used the day 2 serum FSH concentration to
      determine the dose of HMG administered in women under 40 years. If the FSH
      concentration was below 9 IU/l, a constant dose of 150 IU HMG were administered;
      if above 9 IU/l a constant dose of 300 IU HMG was used. Women over the age of 40
      years were given 300 IU HMG regardless of their serum FSH concentration. This
      retrospective study was undertaken to assess whether this approach was beneficial
      for the younger women and also whether the FSH concentration was predictive of
      outcome in older women. The study included all women < 40 years (n = 143) and >
      40 years (n = 32) having their first IVF treatment cycle during 1994. In the
      younger women, there was no difference in the number of cancelled treatment
      cycles (9.7% vs. 7.5%); the number of follicles present (9.6 vs. 8.2); serum
      oestradiol concentration (6971 pmol/l vs. 6686 pmol/l); number of eggs collected
      (7.9 vs. 5.7); number of embryos created (3.7 vs. 3.6); and pregnancy rate (13.5%
      vs. 15%) between women with normal (n = 103) or elevated (n =40) FSH
      concentrations. By using the serum FSH concentration to select women in whom a
      poor response was expected, and administering a higher dose of HMG, a similar
      ovarian response was produced and the pregnancy rate was similar to those in
      women with normal FSH concentrations. Women over 40 years with elevated serum FSH
      concentrations (n = 17) had a significantly (P < 0.05) higher cancellation rate
      (17.6% vs. 0%) and fewer number of eggs collected (6.9 vs. 2.5) than the group
      with normal FSH concentrations (n = 15). One woman conceived in each group. These
      findings confirmed previous studies showing that the serum FSH is predictive of
      ovarian response. This study confirmed the value of measuring the day 2 serum FSH
      concentration as a predictor of response; and it provides a scientific approach
      to determine the dose of HMG administered for IVF stimulation. A satisfactory
      response to induction of ovulation will be achieved using 150 IU HMG in women
      with FSH < 9 IU/l but if the FSH is raised i.e. above 9 IU/l, 300 IU is required
      to achieve a similar response.

PMID- 15511820
TI  - Percutaneous management of lymphocoeles following pelvic lymphadenectomy for
      cervical carcinoma.
AB  - Eighteen patients with 26 pelvic lymphocoeles following radical hysterectomy
      underwent percutaneous therapeutic intervention with either needle aspiration, or
      catheter drainage. In eight patients a percutaneous needle aspiration under
      sonographic control was performed. Five out of eight patients were successfully
      managed with needle aspiration, three of them requiring repetitive aspirations.
      Thirteen patients, with a total of 21 lymphocoeles underwent catheter drainage.
      Seventeen of the 21 lymphocoeles completely resolved. Redrainage was performed in
      four cases and it was successful in two of them. The duration of the catheter
      drainage was 8 to 34 days. Nine of the lymphocoeles were infected at initial
      drainage. Two patients underwent surgery because of increased volume of output.
      Percutaneous drainage is a safe and effective method and should be considered as
      the initial treatment for all patients with postoperative lymphocoeles.

PMID- 15511821
TI  - Menarcheal age of school girls in the city of Jeddah, Saudia Arabia.
AB  - In 1995 a survey was conducted in four schools in the city of Jeddah to determine
      the age of menarche in this population. Nine hundred and twenty-nine girls were
      studied. The mean age at menarche was 15.1 years, and this was later than most
      other Arabic countries and most Western countries, Social class was found to
      influence age at menarche, but the differences in relation to family size did not
      reach statistical significance. The reason for differences between population is
      discussed.

PMID- 15511822
TI  - Selenium and recurrent miscarriage.

PMID- 15511824
TI  - Combined intrauterine and broad ligament ectopic pregnancy.

PMID- 15511823
TI  - Treatment of menorrhagia by transcervical laser ablation of the endometrium.

PMID- 15511825
TI  - Recurrent tubal pregnancy in a woman with endometriosis and unprotected coitus.

PMID- 15511826
TI  - Vault prolapse repair by suspension to Cooper's ligament.

PMID- 15511827
TI  - Gonadotrophin-resistant ovary syndrome (Savage syndrome).

PMID- 15511828
TI  - Chronic uterovaginal prolapse: preoperative treatment.

PMID- 15511829
TI  - Blood loss at emergency caesarean section.

PMID- 15511834
TI  - Thromboelastography in abruptio placentae.
AB  - The purpose of this study was to document thromboelastographic (TEG) changes in
      abruptio placentae and to compare these results with that of conventional tests
      used to monitor coagulation. This was a prospective study of 30 patients with
      abruptio placentae. All coagulation investigations including the TEG were
      performed on admission, immediately following delivery, and after periods of 4
      hours and 24 hours. Results showed that standard coagulation tests detected
      coagulation abnormalities except the platelet count returned to normal limits
      within 24 hours of delivery. There was strong correlation between fibrinogen
      levels and the TEG parameters, ma and k time (r=0.8). There was moderate
      correlation between platelet count and ma (r=0.6). In conclusion, minor
      abnormalities in the clotting profile are clinically unimportant. The TEG does
      not detect such minor abnormalities because of its inherent ability to test the
      coagulation cascade as a whole. Major abnormalities are clinically relevant and
      the TEG detect 75% of them. Further, the TEG establishes the diagnosis of
      hypercoagulability an early sign of disseminated intravascular coagulation.
      Although standard laboratory tests are still necessary to detect coagulation
      abnormalities on admission, the TEG is a useful test in large obstetric units
      where laboratory results are not immediately available for the purposes of
      monitoring and treating ongoing coagulation defects.

PMID- 15511835
TI  - A study of alpha-human atrial natriuretic peptide in normal pregnancy and in pre
      eclampsia.
AB  - The object of this study was to compare plasma levels of alpha-human atrial
      natriuretic peptide (ANP) in patients with pre-eclampsia, normal pregnant women,
      and healthy non-pregnant women. This was an observational study carried out at
      Llandough Hospital, Cardiff, Wales on 85 age-matched women divided into three
      groups (30 patients with pre-eclampsia, 30 healthy pregnant women in the third
      trimester and 25 healthy non-pregnant women). Plasma ANP concentration was
      measured between 14.00 and 16.00 hours, in the recumbent position using pre
      extraction radioimmunoassay. The following measurements were also performed:
      blood urea, serum creatinine, serum uric acid and serum sodium in all study
      subjects and 24-hour urinary protein in pregnant women. All women were eating a
      normal diet. It was shown that plasma ANP levels were significantly higher in
      healthy pregnant women in the third trimester of pregnancy than in non-pregnant
      women (18.12 +/- 7.36 vs. 13.68 +/- 6.41 pmol/l, P < 0.05). This difference was
      also observed in pre-eclamptic women (17.6 +/- 12.06 pmol/l vs. 13.68 +/- 6.41
      pmol/l, P < 0.05) but the plasma hormone levels were not significantly different
      from healthy pregnant women. In all pregnant women, plasma ANP level was related
      to the gestational age and birth weight as shown by the regression coefficient (+
      0.39,-0.26 respectively, P < 0.05). In pre-eclamptic patients, there was no
      relationship between the severity of hypertension, assessed by the level of
      systolic and diastolic blood pressure, serum uric acid level and amount of
      proteinuria, and log (plasma) ANP levels. There was a significant negative
      correlation between serum sodium level and log (plasma) ANP level in all pregnant
      subjects (r=- 0.51, P < 0.05). Compared with non-pregnant women, plasma ANP
      levels are increased during the third trimester of normal pregnancy and in
      pregnancies complicated by pre-eclampsia. A relationship between ANP and pre
      eclampsia seems unlikely but ANP is probably involved in the regulation of sodium
      and water balance in normal pregnancy and in pre-eclampsia.

PMID- 15511836
TI  - Does closure of the peritoneum during caesarean section influence postoperative
      morbidity and subsequent bladder adhesion formation?
AB  - The charts of 100 patients who underwent a second lower segment caesarean section
      were reviewed. In 50 patients both the parietal and visceral peritoneum had been
      closed during the first and second caesarean sections and in the remaining 50
      patients, it had been left open. The incidence of adhesions was found to be 28%
      in the closed group (n=50), compared with only 14% in the open group (n=50).
      Operative time was prolonged by closing the peritoneum, an average of 52.2
      minutes in the closed group compared with 44.1 minutes in the open group, P <
      0.05. The incidence of urinary tract infection, endometritis, wound infection and
      respiratory tract infection in the postoperative period was similar in both
      groups. We conclude that closure of the peritoneum at caesarean section is
      unnecessary and may in fact promote adhesion formation and so the simpler
      technique of leaving it open should be adopted.

PMID- 15511837
TI  - Born before arrival (BBA) in Trinidad-a seven year case-control study.
AB  - A retrospective case-control study was made of 326 babies born before arrival
      (BBA) at hospital, in a Caribbean developing country. Each baby born before
      arrival was matched with hospital-delivered controls within the same week of
      delivery. Control group 1 (n=302) was matched by maternal age and parity and
      control group 2 (n=262) by gestational age and fetal birth weight. BBA occurred
      significantly more often in Afro-Caribbean when compared with those of Indo
      Caribbean origin and was more common in grand multiparous women, those who had
      poor antenatal care and those who had a similar previous event. Perinatal
      mortality was more common than in the control groups. Unlike other studies, young
      maternal age and marital status were not significant contributing factors. These
      findings suggest that clinical features exist for identification of women at high
      risk for BBA which can therefore assist in its prevention and attendant serious
      consequences.

PMID- 15511838
TI  - Retained placenta and associated risk factors.
AB  - In a retrospective study, the factors that might influence the retention of
      placenta such as age, parity, antenatal abnormalities, labour onset and duration,
      history of uterine surgery and previous retained placenta, were studied in 146
      patients with retained placenta. Three hundred women who were delivered vaginally
      without retained placenta were similarly evaluated under the same conditions. The
      results showed (in descending order of significance), history of retained
      placenta, previous uterine surgery, preterm delivery, age above 35 years,
      placental weight less than 601 g, pethidine use in labour, labour induction and
      parity of more than five to be associated with retained placenta. The existence
      of some or all these risk factors in a pregnant woman should alert the
      obstetrician about the possibility of retained placenta in labour.

PMID- 15511839
TI  - The factors associated with effective folic acid prophylaxis in the peri
      conceptional period in women attending an ante-natal clinic.
AB  - The aim of this study was to examine whether folic acid supplements had been
      taken and dietary folate intake increased in 662 pregnant women attending the
      antenatal clinic at St Mary's Hospital, Portsmouth. An assessment was also made
      of the factors that influenced correct compliance with the recommendations of the
      Expert Advisory Group on folic acid. Thirty-seven percent (245/662) women had
      taken folic acid supplements and 26.4% (175/ 662) increased their dietary folate
      before or during early pregnancy. The majority of women who commenced folic acid
      supplements after conception did so after the neural tube had closed (220/247).
      Women were more likely to have adhered to the Expert Advisory Group's
      recommendations if the pregnancy was planned, the woman was primiparous, there
      was no past or family history of neural tube defect and the patient had the
      correct existing knowledge of folic acid prophylaxis. The relevance of these
      findings to the current Health Education Authority's folic awareness campaign is
      discussed.

PMID- 15511840
TI  - Compliance with the peri-conceptional folic acid supplementation guidelines.
AB  - This audit of peri-conceptional folic acid use in early pregnancy demonstrates
      inadequacies in both awareness of and compliance with the Department of Health
      guidelines. If the benefits of folic acid are to be fulfilled then additional
      efforts to improve public awareness are required.

PMID- 15511842
TI  - Breech delivery at term: do the perinatal results justify a trial of labour?
AB  - This is a retrospective study conducted at Princess Badee'a Teaching Hospital in
      North Jordan to compare neonatal loss and morbidity in term singleton breech
      infants delivered either vaginally or by caesarean section. In this study, all
      singleton term breech presentation at 37 completed weeks' gestation were
      reviewed. Three hundred and eight singleton term babies, presenting by the breech
      were studied. Intrapartum deaths, neonatal deaths and Apgar scores in vaginal and
      caesarean delivery were compared. After exclusion of infants with lethal
      congenital malformations and antenatal stillbirths, the incidence of intrapartum
      and neonatal deaths associated with vaginal births was 3.5% compared with 1.3% in
      infants born abdominally. The number of low Apgar scores were similar in both
      groups. We concluded that caesarean section for term singleton breech
      presentation is associated with good neonatal outcome and this may influence the
      decision of obstetricians about the mode of delivery.

PMID- 15511841
TI  - Platelet reactivity is increased in mild gestational diabetes compared with
      normal pregnancy.
AB  - The purpose of this study was to measure blood platelet aggregation in pregnant
      women with gestational diabetes and its correlation with normal pregnancies. The
      study group included 10 women with diabetes of pregnancy and a group of 10
      healthy pregnant women. We used the method of adenosine diphosphate (ADP)
      platelet stimulation with three different ADP solutions. The mean platelet
      aggregation and time in seconds was measured in each patient with the three
      different solutions. The analysis of our results showed that platelet activity
      was statistically increased (P < 0.001) in the group of diabetics compared with
      the group of normal pregnancies. Our conclusion is that platelet activity in
      patients with gestational diabetes appears to be enhanced, probably as a result
      of a disturbance in the equilibrium between prostacyclin and thromboxane.

PMID- 15511843
TI  - Outcome of twin pregnancies in Maiduguri, Nigeria.
AB  - In a retrospective study of twin births in the University of Maiduguri Teaching
      Hospital from January 1982 to December 1990, there was an incidence of twins of
      1/76 with a perinatal mortality rate of 118/1000. The major risk factors were
      shown to be preterm delivery and low birth weight, absence of antenatal care,
      failure to diagnose before the onset of labour, birth asphyxia, retained second
      twin and malpresentation.

PMID- 15511844
TI  - Passive cigarette smoking in pregnancy.

PMID- 15511845
TI  - Does methadone affect pregnancy outcome?

PMID- 15511846
TI  - Measurement of amniotic fluid volumes using echo-planar imaging.

PMID- 15511847
TI  - Cardiac output monitoring during vaginal delivery.

PMID- 15511848
TI  - Postpartum exploration of the genital tract under general anaesthesia reviewed.

PMID- 15511850
TI  - Severe intrauterine growth retardation due to taut triple knots of the umbilical
      cord.

PMID- 15511849
TI  - The clinical significance of reduced amniotic fluid index in post-term pregnancy
      a retrospective study.

PMID- 15511851
TI  - Addison's disease in pregnancy presenting as hyperemesis gravidarum.

PMID- 15511852
TI  - Ultrasound findings in placenta percreta.

PMID- 15511853
TI  - Novel treatment of extensive thrombo-embolic disease in pregnancy with a
      temporary vena cava filter.

PMID- 15511854
TI  - Vasa praevia: fatal fetal exsanguination.

PMID- 15511855
TI  - Acute fatty liver of pregnancy.

PMID- 15511857
TI  - Late postnatal pre-eclampsia.

PMID- 15511856
TI  - A successful pregnancy in renal disease.

PMID- 15511858
TI  - The determination of phospholipase A2 enzyme activity in the vaginal secretions
      of pregnant and non-pregnant women with bacterial vaginosis-and in culture
      exudates of its causative organisms.
AB  - Bacterial vaginosis (BV) is presently being cited as a probable cause of
      premature labour, where it is thought that an abnormal excess of phospholipase A2
      enzyme (PLA2 ), generated by infecting organisms, prematurely liberates
      prostaglandins, which trigger-off the labour process. PLA levels of pregnant and
      non-pregnant women, with and without BV infection were compared. The in vitro
      concentrations of PLA2 in broth cultures of infecting organisms were also
      measured. Mean PLA2 level in non-infected pregnant women was 777 units per mg but
      was raised to 1226 U/mg in those with BV ( P= <0.001). Mean level in non-infected
      normal women was 21 U/mg, but was raised to 97 U/mg in those having BV ( P=
      <0.001). PLA2 concentrations in broth cultures of the causative organisms showed
      that most Bacteroides strains produced the enzyme, having a mean concentration of
      95 U/mg, but that it was generated by only 34% of Gardnerella vaginalis strains,
      their mean concentration being 32 U/mg.

PMID- 15511859
TI  - Reversal of female sterilisation experience in a district general hospital.
AB  - Forty-five women who had microsurgical reversal of tubal sterilisation in New
      Cross Hospital Wolverhampton, between January 1986 and December 1992, were
      analysed to determine the success rate and the influencing factors. These women
      were followed-up until September 1994. More than 80% of the women were sterilised
      before the age of 30, and more than 80% sought reversal because of change of
      relationship. The overall pregnancy rate was 57.8% (intrauterine 51.1%, ectopic
      6.7%). There were 17 (37.8%) live births. Intrauterine pregnancy rate was 100%
      (6/6) for the reversal of previous Filshie clip sterilisation, 50% (17/34) for
      previous Falope ring application and 0% (0/5) for previous Pomeroy method (P <
      0.001). Analysis according to the site of anastomosis showed that the isthmic
      isthmic anastomosis had an intrauterine pregnancy rate of 87.5% (7/8), isthmic
      ampullary: 48.4% (15/31) and ampullary-ampullary: 16.7% (1/6), (P < 0.02).
      Sterilisation-reversal interval had no significant influence on the intrauterine
      pregnancy rate.

PMID- 15511860
TI  - Human endometrial nuclear estrogen receptors among Norplant implant users.
AB  - Twenty-four parous women were included in this study. Sixteen cases were using
      the Norplant implant contraceptive system for more than 6 months (Group A) while
      eight cases served as matched controls in the secretory phase (Group B). Norplant
      implant users belonged to one of two equal subgroups according to whether they
      experienced regular menstrual bleeding (Subgroup A1) or prolonged episodes of
      amenorrhoea (Subgroup A2). Endometrial samples were processed for nuclear
      oestrogen receptor assay and for evaluation of the receptor's binding affinity to
      oestrogen. The results showed marked reduction in endometrial nuclear oestrogen
      receptors in Norplant users compared with controls as the majority of users had
      undetectable receptor levels. This down-regulation effect was significantly more
      pronounced among women with prolonged episodes of amenorrhoea. The affinity
      section of the study revealed no significant differences between groups or
      subgroups probably due to the small number of subjects with detectable receptor
      concentrations for comparison. These data may help in the understanding of
      contraceptive mechanisms and menstrual associated problems, and in the
      development of therapeutic measures.

PMID- 15511861
TI  - Endometriosis of the abdominal wall: a clinical-pathologic contribution.

PMID- 15511862
TI  - Retropubic colposuspension in the treatment of stress urinary incontinence:
      result of a long-term follow-up.

PMID- 15511863
TI  - Atypical polypoid adenomyoma of the uterus: clinical and histological findings of
      three postmenopausal cases.

PMID- 15511864
TI  - A case of myomectomy complicated by disseminated intravascular coagulation.

PMID- 15511866
TI  - An unusual complication of laparoscopic salpingostomy for ectopic pregnancy.

PMID- 15511865
TI  - Papillary metaplasia and decidualisation of the endometrium in a woman receiving
      tamoxifen and megoestrol acetate.

PMID- 15511867
TI  - Primary abdominal ectopic pregnancy.

PMID- 15511868
TI  - Testicular feminisation syndrome with persistent fallopian tubes and full length
      vagina.

PMID- 15511869
TI  - Aggressive angiomyxoma of the vulva.

PMID- 15511870
TI  - Grand multiparity-is it an obstetric problem?

PMID- 15511873
TI  - A random controlled trial of two different vacuum extractor pumps: new foot pump
      and electric pump.
AB  - Worldwide the vacuum extractor is the instrument used most commonly for assisted
      vaginal delivery. Many institutions use electric pumps in preference to the
      original hand pump, considered by some to be inefficient (requiring an
      assistant). A new foot pump has been developed. In a controlled comparison with a
      standard electric pump, no differences in efficiency were found.

PMID- 15511874
TI  - Characteristics and outcome of deliveries by forceps after failed ventouse.
AB  - With the increasing use of the ventouse, it is becoming common for deliveries to
      be completed by the application of forceps. We present 48 cases delivered by
      forceps after a failed ventouse and compare these with 63 cases delivered by
      forceps only. There was significantly higher incidence of caesarean sections and
      cephalhaematoma in the group where forceps delivery was attempted after a failed
      ventouse compared to those delivered with forceps only.

PMID- 15511875
TI  - Maternal opiate use: pregnancy outcome in patients managed by a multidisciplinary
      approach.
AB  - The outcome of 39 pregnancies in 35 pregnant opiate users is reported. These
      women were managed by a multidisciplinary team resulting in 36 live births, one
      stillbirth. one spontaneous miscarriage and one induced abortion. The majority of
      patients were stabilised on methadone before the third trimester. The women were
      characterised by a high prevalence of previous obstetric and medical problems,
      43.6% of the women were single and 87.2% unemployed The mean (SD) gestational age
      was 38.2 +/- 2.3 weeks, mean (SD) birth weight was 2980 +/- 543 g. There were
      eight cases of preterm deliveries, all occurred beyond 32 weeks' gestation. One
      preterm and two term babies had a birth weight below the 10th centile. Thirty-two
      (86.5%) women had a normal vaginal delivery, seven (10.8%) had caesarean section
      and one (2.7%) had forceps delivery. Comprehensive antenatal care in conjunction
      with methadone maintenance appears to result in a pregnancy outcome comparable
      with a general obstetric population.

PMID- 15511876
TI  - Fetal/neonatal alloimmune thrombocytopenia: a continuing challenge.
AB  - Fetal/neonatal alloimmune thrombocytopenia is the platelet counterpart of the red
      cell disorder, haemolytic disease of the fetus and newborn. Unlike Rhesus
      pregnancies, first pregnancy is commonly affected. It is a progressive disease
      and can cause severe fetal damage, late fetal and neonatal loss and severe
      handicap. No screening programme is currently available and the diagnosis is
      often delayed. Testing for platelet antibodies in those mothers whose babies are
      thrombocytopaenic is necessary for early detection of this condition.

PMID- 15511877
TI  - Agreement between different frequencies of measurements in ambulatory blood
      pressure monitoring.
AB  - The purpose of this study was to determine the degree of agreement among
      different frequencies of blood pressure measurements (FoM) in 24-hour ambulatory
      blood pressure monitoring (ABPM) in their ability to obtain useful clinical
      information. ABPM records were obtained with a Del Mar IV Avionics device from 49
      hospitalised preeclamptic women with a FoM of 7 per hour (high-FoM). With these
      records, we simulated two sets of data as if measurements had been recorded at a
      rate of 1 measurement per hour (low-FoM) and of 2 per hour (medium-FoM).
      Diastolic blood pressure > 89 mmHg defined hypertension and > 109 mmHg, severe
      hypertension The median and 25th and 75th centiles for the differences in
      hypertensive rate detected (expressed as percentage points) between lowFoM vs.
      high-FoM was 0.00 (- 3.4-3.00) and between medium-FoM vs. high-FoM,- 1.04 (- 3.7
      1.5). The agreement in the detection of severely affected patients was 85% (CI
      95%: 74-96) between low-FoM and high-FoM and 87% (CI 95%: 77-98), between medium
      FoM and high-FoM. Average blood pressure was similar in the three FoMs studied at
      day-time and night-time. We did not find any strong argument to perform ABPM at a
      high-FoM. Lower FoM are more comfortable for the patient and could reduce
      equipment deterioration, while providing equivalent information to that supplied
      by high-FoM.

PMID- 15511878
TI  - Serum concentrations of iodine, thyroxine (T4), triiodothyronine (T3),
      thyrotropin (TSH) and insulin-like growth factor 1 (IGF-1) during the last
      trimester of pregnancy, during labour, and in early puerperium of women with
      normal pregnancy or with intrauterine growth retardation (IUGR).
AB  - In women with intrauterine growth retardation (IUGR), insulin-like growth factor
      1 (IGF-1) concentrations tended to reduce during the last trimester of pregnancy.
      Parameters of thyroid function in maternal serum were not distinctly influenced
      by IUGR, except for high concentrations of iodine. Triiodothyronine (T3)
      concentrations in cord blood of normal pregnancies was significantly lower than
      maternal concentrations, but was relatively high when the fetus was growth
      retarded. The results are discussed in connection with changes of thyroid
      function and changes of IGF-1 during pregnancy.

PMID- 15511879
TI  - Maternal deaths in teenage mothers.
AB  - In developing countries such as Zambia, teenage pregnancy is common and
      dangerous. In this study, out of 677 teenage mothers 33 died. The causes of this
      alarming mortality are documented and show the influence of sepsis, obstructed
      labour and uterine rupture. Malaria was an important associated cause. Only a
      major education programme with discouragement of pregnancy in young girls is
      likely to influence this distressing problem.

PMID- 15511880
TI  - Survey of the deliveries of immigrant women from developing countries in the 2nd
      Institute of Gynaecology and Obstetrics, University of Rome, 'La Sapienza',
      Italy.
AB  - Five hundred and forty-four immigrant women, admitted from 1983 to 1993 to the
      2nd Institute of Obstetrics and Gynaecology of Rome University, were enrolled in
      the study. Africa and East Europe were the most common places of birth. Seventy
      five per cent of women gave birth spontaneously, and a caesarean section was
      performed in 22.2%. The frequency of spontaneous delivery and caesarean section
      was about the same among Italian and immigrant women.

PMID- 15511881
TI  - Transabdominal cervicoisthmic cerclage: the Riyadh Armed Forces Hospital
      experience.
AB  - Between 1985 and 1996, 17 transabdominal cervicoisthmic cerclage procedures were
      performed and followed up through 28 pregnancies at Riyadh Armed Forces Hospital,
      Riyadh, Kingdom of Saudi Arabia. Fourteen procedures were carried out during
      pregnancy and three preconceptionally. Twenty-four pregnancies continued beyond
      36 weeks of gestation and three were premature deliveries. The material used was
      an infant feeding tube size 6 and the knot was tied posteriorly. The sole
      miscarriage was at 6 weeks' gestation. All deliveries were by caesarean section.
      Fetal survival was 92%. In conclusion, abdominal cerclage is an effective and
      safe operation which helped the pattern of pregnancy wastage to be restored to
      normal in selected patients.

PMID- 15511882
TI  - Emergency autologous blood transfusion in the management of ruptured ectopic
      pregnancy.
AB  - Thirty-three cases of ruptured ectopic pregnancies treated by emergency
      autologous blood transfusion were compared with 85 cases treated by homologous
      blood. The postoperative outcome was satisfactory and the duration of hospital
      stay was similar in both groups. However, the quantity of blood transfused in
      those who received autologous blood was significantly higher than in those
      transfused with homologous blood ( P 0.02). Because of this experience we
      advocate greater use of intra-operative blood salvage and autotransfusion, even
      when banked homologous blood is available, in the management of ruptured ectopic
      pregnancy.

PMID- 15511883
TI  - Successful removal of large ovarian cysts using endoscopic techniques in the
      second trimester of pregnancy.

PMID- 15511884
TI  - A challenging diagnosis.

PMID- 15511885
TI  - Breast cancer in pregnancy.

PMID- 15511886
TI  - Wolff-Parkinson-White syndrome in the puerperium.

PMID- 15511888
TI  - Locked twins: a successful outcome after applying the Zavanelli manoeuvre.

PMID- 15511887
TI  - Wernicke's encephalopathy as a complication of hyperemesis gravidarum.

PMID- 15511889
TI  - Fetal limb arterial occlusion in diabetic pregnancy.

PMID- 15511890
TI  - Four spontaneous intrauterine pregnancies following right and left
      salpingectomies for ectopic pregnancies.

PMID- 15511891
TI  - Torsion of an epiploic appendage presenting as adnexal torsion in pregnancy.

PMID- 15511892
TI  - Acute megakaryoblastic leukaemia in pregnancy presenting as relapse of chronic
      idiopathic thrombocytopenic purpura.

PMID- 15511893
TI  - Management of kyphoscoliosis and respiratory failure in ventilatory dependent
      pregnancy.

PMID- 15511895
TI  - Inevitable myomectomy in pregnancy.

PMID- 15511894
TI  - Cabergoline treatment for a large macroprolactinoma throughout pregnancy.

PMID- 15511896
TI  - Vaginoplasty by inverted perineal and labia minora flaps-a retrospective study.
AB  - Absence of the vagina occurs most frequently in the Rokitansky-Kuster-Mayer (RKM)
      syndrome. Since Kuster has reviewed the literature in 1910 many techniques have
      been described to create a neovagina. We describe a technique in which both a
      part of the labia minora and of the perineal skin are used as flaps to cover the
      neovagina and report on the long-term outcome in a series of 16 patients with RKM
      syndrome treated with this technique. No intra-operative or immediate
      postoperative complications were recorded. The average depth of the neovagina was
      8 cm, at the end of the operation and 1 year later. After 3 months the neovagina
      was completely lined with vaginal epithelium. In six out of 16 patients scar
      formation and polypoid formation was observed at the apex of the neovagina. This
      could be successfully handled by excision and coagulation in all six cases. Ten
      patients reported a satisfactory sexual life. The technique is simple and easy to
      perform. The anatomical result and sexual gratification was outstanding in two
      thirds of the patients. We conclude that flaps derived from the genital region
      offer the most physiological tissue for construction of a neovagina.

PMID- 15511897
TI  - Anaerobic (bacterial) vaginosis and premalignant disease of the cervix.
AB  - Nitrosamines are carcinogenic substances found in cigarette smoke, and it is
      known that female smokers have an increased risk of cervical carcinoma and
      premalignant change. Nitrosamines may also be formed due to the combination of
      amines and nitrites in an acidic medium. This study has shown a statistically
      significant association between anaerobic vaginosis which produce amines and
      cervical intraepithelial neoplasia 2 and 3. In addition nitrate reducing
      organisms are found in the acidic lower genital tract in a significant number of
      cases. It is therefore theoretically possible that nitrosamines may be an
      important agent in the development of premalignant disease of the cervix.

PMID- 15511898
TI  - A critical evaluation of follow-up of women treated for endometrial
      adenocarcinoma.
AB  - A retrospective review of all women diagnosed with endometrial adenocarcinoma
      over a 5-year period was performed. One hundred and eleven women had not
      defaulted from follow-up and were thought to be disease-free following primary
      treatment. Seventeen (15.3%) of this group of women developed recurrent disease;
      four of these being detected in asymptomatic patients at routine follow-up
      visits. Women with asymptomatic recurrences had a significantly better survival
      than those presenting with symptoms (25% vs. 8%, P = 0.048). On the basis of
      previous findings, a limited hospital surveillance protocol was applied
      retrospectively to these patients with an estimated financial saving of over 2500
      per annum. However, as one asymptomatic recurrence was detected by vault cytology
      during the 2 years after primary treatment, it may be worthwhile continuing to
      perform vault cytology during this period.

PMID- 15511899
TI  - Role of chromosome heteromorphism in early recurrent miscarriages in the Middle
      East.
AB  - To identify the role of chromosome polymorphism in miscarriages, an analysis was
      carried out on 774 couples; 391 of them with two or more miscarriages and 383
      serving as control. All couples were taken from two separate ethnic groups
      residing in the United Arab Emirates (UAE): 199 cases and 194 controls came from
      the indigenous population who are UAE nationals (Arabs) whilst 192 cases and 189
      controls came from the Asian expatriate population residing in the UAE (Asians).
      Out of 391 cases, six Arab and three Asian couples were excluded because at least
      one partner had a chromosomal aberration. From the control group four Arab and
      four Asians were excluded for similar reasons. The remaining 757 couples were
      analysed to detect the presence of chromosomal heteromorphism in one or both
      partners. The results suggest that chromosomal heteromorphism was significantly
      increased in the Arab study population (P < 0.05). Two heteromorphisms, 9qh and
      inversion (9)(p11q13) seem to be marginally related to recurrent miscarriages and
      only in the Arab study population. No differences were found in the distribution
      of chromosomal heteromorphism in couples analysed in relation to the number of
      miscarriages (two or more).

PMID- 15511900
TI  - Patient-based evaluation of a colposcopy information leaflet.
AB  - A questionnaire survey of new patients attending the colposcopy clinic of a
      teaching hospital was carried out. The intention was to evaluate the information
      leaflet routinely sent to women who have been referred for colposcopy because of
      abnormal cervical smear results and use the findings to propose changes that will
      make the leaflet more suitable, effective and patient-friendly. The majority of
      the respondents received (90%), read (90%) and understood most or all (96%) of
      the information leaflet. Patients who received the leaflet performed better in
      the knowledge quiz than those who did not (P < 0.0001). Of the 111 patients who
      received and read the leaflet 50 (45%) found it reassuring or very reassuring and
      58 (52%) thought it made them less anxious. On the contrary 20 (18%) patients
      found the leaflet worrying or very worrying and 33 (30%) thought it made them
      more anxious. Overall, 91 (82%) patients found the leaflet helpful or very
      helpful and 99 (89%) were satisfied with the information provided. The commonest
      difficulties with the leaflet identified by patients concerned the use of
      abbreviations and technical terms. We found the leaflet to be a useful method of
      providing information for patients before colposcopy. Whilst the leaflet appeared
      to have a major impact on patients' knowledge about abnormal smears and
      colposcopy, its effect in reducing anxiety was less pronounced.

PMID- 15511901
TI  - Transvaginal ultrasound measurement of endometrial thickness and endometrial
      pipelle sampling as an alternative diagnostic procedure to hysteroscopy and
      dilatation and curettage in the management of post-menopausal bleeding.
AB  - In order to evaluate pipelle endometrial sampling combined with ultrasound
      measurement of endometrial thickness as an initial diagnostic procedure in the
      assessment of endometrial pathology in patients presenting with postmenopausal
      bleeding, 50 consecutive patients were studied prospectively. In each patient
      measurement of endometrial thickness and pipelle endometrial biopsy were
      performed as an out-patient procedure before hysteroscopy and dilatation and
      curettage (D&C). The diagnostic sensitivity with pipelle endometrial sampling
      alone in detecting endometrial pathology was 25% with a specificity of 100%. The
      measurement of endometrial thickness had a sensitivity of 62% with a specificity
      of 87.8%. Pipelle sampling combined with endometrial thickness increased the
      sensitivity to 87.5% with a specificity of 87.8%. Therefore, we suggest that
      pipelle sampling combined with sonographic measurement of endometrial thickness
      is an acceptable, less invasive alternative to hysteroscopy and D&C as a first
      line investigation in the management of post-menopausal bleeding.

PMID- 15511902
TI  - Atypical presentation of primary fallopian tube carcinoma.

PMID- 15511903
TI  - Failure of conservative treatment with methotrexate for interstitial pregnancy
      despite progressive decrease of serial serum betaHCG.

PMID- 15511904
TI  - Pelvic calcification-fibroid or rectal foreign body?

PMID- 15511905
TI  - Malignant transformation within a dermoid cyst.

PMID- 15511906
TI  - Vaginal leiomyoma.

PMID- 15511907
TI  - Microglandular hyperplasia of the cervix mimicking trophoblastic proliferation.

PMID- 15511908
TI  - Management of refractory pre-menstrual syndrome using subcutaneous oestradiol
      implants and levonorgestrel intrauterine systems.

PMID- 15511909
TI  - Retroperitoneal tumour presenting as ovarian cyst.

PMID- 15511910
TI  - A comparison of cryocauterisation, laser vaporisation and large loop excision of
      the transformation zone for the treatment of cervical intraepithelial neoplasia.

PMID- 15511911
TI  - Royal College of Physicians of Edinburgh/Royal College of Obstetricians and
      Gynaecologists: consensus conference on anti-D prophylaxis. 7 & 8 April 1997.

PMID- 15511914
TI  - Stillbirth and caesarean section.
AB  - In one health region between 1991 and 1996, 105 (11%) of all stillbirths were
      delivered by caesarean section. Forty-eight (46%) were unexpected at the time of
      birth, two of whom were macerated. Most of the macerated stillbirths were one of
      a multiple pregnancy, while 22 of the fresh stillbirths were delivered by
      caesarean section prior to the onset of labour. Twenty-one caesarean sections
      were performed because of failed attempts to induce labour, or at the request of
      the mother. The unexpectedly high rate of stillbirths delivered by caesarean
      section could be reduced by improved methods and understanding of antenatal and
      intrapartum fetal monitoring and techniques for inducing labour.

PMID- 15511915
TI  - Is surgical intervention in acute cholecystitis in pregnancy justified?
AB  - Over a three-year period 49 cases were admitted to our hospital with an acute
      abdomen in pregnancy due to cholecystitis. In this article we compare surgical
      treatment with medical treatment and consider the aetiology of the high
      prevalence. Out of the 49 cases admitted, 15 cases (31%) had emergency
      cholecystectomy within the first week and 34 cases (69%) were treated
      conservatively of whom 24 relapsed many times and had to be readmitted to the
      hospital (mean number of admissions was 4 +/- 1.4 and the mean hospital stay was
      8 +/- 2.3 days) and of the remaining 10 on conservative management, three had
      emergency cholecystectomy and seven reached term safely. The maternal morbidity
      is significantly less in the surgically treated group (P < 0.0001) but the
      perinatal outcome failed to show any significant difference. The frequency of
      acute cholecystitis in pregnancy (0.33%) is high in comparison with other
      studies. Although tocolytics were used in 13 cases they did not improve the fetal
      outcome significantly and had maternal and fetal side effects. In conclusion
      early surgical intervention is recommended and the use of tocolytics did not
      improve the perinatal outcome.

PMID- 15511916
TI  - Audit of infective morbidity following caesarean section at a district general
      hospital.
AB  - This paper sets out to audit infectious morbidity before and after introduction
      of a policy of antibiotic prophylaxis following emergency and elective caesarean
      section in a district general hospital in Scotland with approximately 3800
      deliveries a year. In the first 'loop of audit', case notes of 200 consecutive
      patients managed during 1992 were studied. Audit loop was completed by studying
      224 patients prospectively in 1993-94 following the introduction of new
      guidelines, which required the intraoperative administration of a single dose of
      intravenous antibiotic, following delivery of the baby. A significantly greater
      proportion of women received prophylactic antibiotics in 1993 compared with 1992
      (81% vs. 14%; Diff= 67%; 95% CI 60%, 74%). The incidence of infection related
      morbidity was significantly reduced after routine antibiotic prophylaxis (28,5%
      vs. 16%; Diff= 12.5%, 95% CI=(4.60%,20.4%). The incidence of wound infection was
      halved in 1993 (9% vs. 17.5% in 1992). None of the patients in 1993 had a serious
      postoperative infection. Postnatal stay was significantly shorter in 1993
      compared with 1992 (P < 0.0001). Although the target of adherence to the
      guidelines of 90% coverage was not met, this audit demonstrates the benefits of
      antibiotic prophylaxis for emergency and elective caesarean sections. Further
      reduction in morbidity may be obtained by strictly implementing the guidelines,
      and also by considering the use of multiple doses of antibiotics.

PMID- 15511917
TI  - Interleukin 1beta in serum of women with preterm uterine contractions.
AB  - Preterm delivery is a major obstetric and public health problem, accounting for
      50-70% of all perinatal deaths. An enzyme-linked immunoassay (ELISA) test was
      used to determine serum interleukin 1b (IL-1b) levels in 32 women with preterm
      contractions compared with 26 women in term labour and 11 normal preterm pregnant
      women. Women with preterm contractions (with or without treatment) had
      significantly lower mean serum levels of IL-1b (23.5 pgr/ml) compared with women
      in term labour (218 +/- 57 pgr/ml), but similar levels to pregnant women not in
      labour at the same weeks of gestation.

PMID- 15511918
TI  - Factors associated with rapid labour in nulliparae.
AB  - The objective of this study was to assess the factors which may influence rapid
      labour in nulliparae. This is a cohort study of 991 consecutive nulliparae who
      were admitted in spontaneous labour with a singleton pregnancy and cephalic
      presentation. The setting was the National Maternity Hospital, Dublin where
      active management of labour is applied to all nulliparae fitting the above
      criteria. Rapid labour of 2 hours or less occurred in 82 patients (8.3%).
      Dilatation of 2 cm of the cervix on admission in labour, gestation of less than
      37 weeks, and diminishing birthweight, were more common in rapid labours compared
      with other labours. Women in rapid labour were not surprisingly less likely to
      require oxytocin augmentation, or to need operative vaginal delivery or Caesarean
      section, receive epidural anaesthesia, or attend antenatal classes, compared with
      other women in labour. Rapid labour was not influenced by the finding that the
      membranes were already ruptured before admission, the time spent at home with
      contractions, or social background. Women with rapid labour were more likely to
      arrive in hospital within 4 hours compared with other women in labour. Rapid
      labour depends on the efficiency of uterine action which is reflected by the
      dilatation of the cervix on admission.

PMID- 15511919
TI  - Elevated serum melatonin levels during human late pregnancy and labour.
AB  - Melatonin (MLT) shows an influence on gonadal steroid genesis, and has soporific
      effects. Serum MLT levels were examined during late pregnancy and 4 days after
      delivery in 25 women. Circulating levels of melatonin were analysed as integrated
      values (areas under the curve [AUC]) over 24 hours, 5 to 2 days before and 4 days
      after delivery. Antepartum AUCs were significantly increased compared with
      postpartum AUCs. Additionally, MLT levels were measured every 2 hours in a
      subgroup of 11 women during spontaneous labour between 08.00 and 12.00 h at a
      time when physiological serum MLT levels were low. Increased MLT levels were
      determined and compared to MLT levels measured in a previous evaluation of the
      antepartum AUCs. Elevated serum MLT levels during late-pregnancy and labour may
      influence the concentration of receptors of gonadal steroids in the gravid uterus
      at term and the psychic perception of painful uterine contractions during labour.

PMID- 15511920
TI  - A prospective evaluation of the value of intrapartum biophysical and Doppler
      parameters in identifying the potentially compromised fetus.
AB  - This study was designed to evaluate the use of the biophysical profile and
      umbilical arterial Doppler in early labour in identifying the potentially
      compromised fetus. Two hundred and forty-two women attending the labour suite in
      early labour were studied. One hundred and fifty-one were in spontaneous labour
      and the remaining 91 had labour induced. All women had intrapartum biophysical
      profile assessment and umbilical arterial Doppler performed. Umbilical arterial
      Doppler and fetal movements were variously identified as being independently and
      significantly associated with adverse perinatal outcomes. Positive predictive
      values for adverse outcomes were however poor. Umbilical arterial Doppler used
      individually or in combination with clinical risk, gave no advantage over the use
      of clinically assigned risk alone in identifying fetuses at risk of subsequent
      adverse outcome. The assignment of clinical risk on admission in labour remains
      the most predictive 'test' for identifying the fetus at risk of subsequent
      adverse outcome. The routine addition of intrapartum biophysical parameters and
      umbilical arterial Doppler as methods of assessment is not justified.

PMID- 15511921
TI  - Transport in vitro fertilisation: three years experience at a district general
      hospital.
AB  - Transport in vitro fertilisation (IVF) is an important development in assisted
      conception. We report our experience of transport IVF treatment from May 1993 to
      April 1996 at Arrowe Park Fertility Centre. A total of 74 patients were treated
      during this period. The main indications of treatment were tubal damage,
      unexplained infertility of more than 3 years duration, polycystic ovarian disease
      and endometriosis. Total number of simulated ovarian cycles were 101. Thirteen
      cycles were abandoned. Eighty-eight transport IVF cycles led to 29 pregnancies,
      giving a live birth rate and on-going pregnancy rate per patient of 31% and per
      cycle rate of 23%. There was one case of severe ovarian hyperstimulation
      syndrome. Of the 74 patients, 70 (95%) patients preferred to have treatment at
      the local hospital. Transport IVF is an effective, efficient and economic way of
      providing assisted conception at district general hospital. The success rate and
      safety of transport IVF are comparable with conventional IVF treatment.

PMID- 15511922
TI  - An appraisal of the appropriateness of the indications for hysterectomy.
AB  - Over a five-year period, 197 hysterectomies were performed at King Khalid
      University Hospital (KKUH). Indications for the procedures vary from menstrual
      disorders and symptomatic fibroids to ovarian malignancy. The most common
      indication was found to be menorrhagia. Among multiple pre-operative indications,
      only the first listed major indication for hysterectomy was chosen. There were
      145 abdominal and 52 vaginal hysterectomies and all were elective gynaecological
      procedures, majority of which were performed on women in their fourth and fifth
      decades of life. Verification of pre-operative diagnosis, when correlated with
      pathological findings, showed that some of the indications for the procedure
      deserve a more critical reappraisal. Since hysterectomy carries substantial
      economic and medical consequences, indications for undertaking the procedure
      deserve more careful scrutiny given the surgical and nonsurgical options that are
      currently available. There may be a need, therefore, to assess the
      appropriateness or otherwise of the use of hysterectomy in many of the patients
      in future.

PMID- 15511923
TI  - Female urethral diverticula.
AB  - Most urethral diverticula should be diagnosed on clinical grounds alone, but
      investigations may be used to confirm the diagnosis in difficult cases, delineate
      the extent of the disease and investigate other entities such as stress
      incontinence. A high index of suspicion is required when assessing women with
      lower urinary tract symptoms to ensure that cases of urethral diverticulum are
      not missed. The cases presented demonstrate that greater awareness of the signs
      and symptoms of this not uncommon disease may facilitate early diagnosis. Our
      cases also show that surgical treatment is effective and worthwhile.

PMID- 15511924
TI  - Community-based post-operative follow-up visit after major surgery for benign
      gynaecological conditions: a prospective study.
AB  - The time from surgery to discharge after major procedures for benign
      gynaecological conditions continues to fall. This small prospective study was
      undertaken to assess the postoperative problems encountered by patients after
      gynaecological surgery for a variety of benign disorders, and the potential of
      the 6-week surgical follow-up to be performed by the patient's family doctor
      rather than the hospital. The patients' and doctors' satisfaction with such care
      was determined. The study showed that follow-up in the community was acceptable
      to both patient and doctor. When problems arose after discharge most patients (
      50%) contacted their family doctor. At the 6-week visit few had physical
      problems, though most (58-100% depending on the Group) felt that a 6-week follow
      up was required. Six-week postoperative follow-up by the family doctor is
      acceptable, and could permit more effective use of hospital specialists, though
      would increase the workload of family doctors.

PMID- 15511925
TI  - A study to evaluate Chlamydia screening in colposcopy clinics.
AB  - A preliminary study of 329 colposcopy patients was conducted to investigate the
      prevalence of endocervical chlamydial infection using the VIDAS Chlamydia Enzyme
      Immune Assay (EIA) and Chlamydia Immune Fluorescent Antigen (IFA) collection
      kits. The overall antigen positive rates of five of the 329 (1.5%) in the study
      group compared exactly with the four out of the 260 (1.5%) in the gynaecological
      outpatient controls. Women in the age group 16-20 years had the highest Chlamydia
      detection rates (7%) followed by those aged 21-30 years (2.3%). Four of the 119
      (3.4%) single women in the study group were Chlamydia antigen positive compared
      with one of the 210 (0.5%) married women (P < 0.005). Among the controls, three
      of the 65 (4.6%) single and one of the 195 (0.5%) married women were positive. In
      both the study and control populations, Chlamydia antigen was more prevalent
      among younger women and non-contraceptive users. Routine screening in colposcopy
      patients may not be cost effective, but a policy of selective screening in young
      single women aged 20 years or less should be considered. Larger sample studies
      using the more specific and sensitive DNA amplification techniques would have
      probably yielded higher detection rates and are recommended.

PMID- 15511926
TI  - Use of an experimental model of chlamydial salpingitis in mice for the evaluation
      of activity of antibiotics and anti-inflammatory drugs on fertility.
AB  - An experimental animal model has been used to study the separate and combined use
      of antibiotics and anti-inflammatories in the treatment of salpingitis. The
      addition of an anti-inflammatory did not seem to help preserve fertility.

PMID- 15511927
TI  - A full term primary ovarian pregnancy.

PMID- 15511928
TI  - Subcutaneous emphysema and pneumomediastinum complicating a normal pregnancy.

PMID- 15511930
TI  - Postpartum urinary retention presenting with signs of deep venous thrombosis.

PMID- 15511929
TI  - Small bowel volvulus and pregnancy.

PMID- 15511931
TI  - Fetal abnormality associated with maternal acute lymphoblastic leukaemia.

PMID- 15511932
TI  - Massive haemorrhage due to placenta praevia accreta: a useful role for
      vasopressin.

PMID- 15511934
TI  - Antenatal care and delivery of a patient with a ventriculo-peritoneal shunt.

PMID- 15511933
TI  - Uterine rupture in labour following surgical termination of pregnancy.

PMID- 15511935
TI  - Vasovagal syncope: an unusual cause of postpartum collapse.

PMID- 15511936
TI  - Isolated congenital pulmonary lymphangiectasis in a dizygotic twin pregnancy.

PMID- 15511937
TI  - Bilateral Sertoli cell tumours presenting as a third primary malignancy.

PMID- 15511938
TI  - Spontaneous haemoperitoneum caused by subserous fibroid.

PMID- 15511939
TI  - Pancreatic pseudocyst: a rare cause of a pelvic mass.

PMID- 15511940
TI  - Intractable vaginal discharge in a schoolgirl.

PMID- 15511941
TI  - Primary ovarian pregnancy associated with mature cystic teratoma.

PMID- 15511942
TI  - Haematometra secondary to endometrial resection mimicking ureteric colic.

PMID- 15511943
TI  - Recurrent atypical polypoid adenomyoma in association with ovarian carcinoma-a
      cautionary tale.

PMID- 15511944
TI  - Leiomyoma of the ovary.

PMID- 15511945
TI  - Female adnexal tumour of probable Wolffian origin.

PMID- 15511948
TI  - Physiology and pathophysiology of lung development.
AB  - Over the past few years, there has been a considerable improvement in our
      understanding of the normal development of the fetal lung and its regulation.
      These advances have occurred mostly through increased knowledge of molecular
      biological mechanisms of growth and differentiation. These advances have also
      resulted in an improvement in our comprehension of the pathological basis of
      various pulmonary diseases. As a result of this new and improved knowledge, new
      and innovative therapeutic modalities are being introduced into clinical
      practice. The introduction of surfactant therapy into the clinical setting was
      one such milestone in neonatal respiratory management. Pulmonary surfactant is
      responsible for stabilising alveoli during normal respiration, thereby preventing
      atelectasis or alveolar flooding. Disease processes which result in an
      insufficiency in surfactant, such as respiratory distress syndrome (RDS) or
      congenital diaphragmatic hernia (CDH), generally carry a very high mortality
      rate. Exogenous surfactant administration reduces both the mortality and
      morbidity associated with RDS and its sequelae, and its efficacy in the treatment
      of CDH is now being evaluated clinically. Moreover, laboratory studies suggest
      that surfactant therapy may be used in combination with other treatments, such as
      tracheal occlusion to promote lung growth in CDH, in order to achieve a maximal
      effect in these complex, multifactorial lung diseases.

PMID- 15511949
TI  - Screening for proteinuria in hypertensive disorders of pregnancy.
AB  - One hundred and fifty patients were recruited to assess the reliability of a
      random urinary dipstick for protein compared with 24 hour urine analysis and to
      determine if a shorter interval of collection is reliable in screening for
      proteinuria in hypertensive disorders of pregnancy. These patients were
      instructed in the collection technique of a 24 hour urine sample. Aliquots were
      taken to represent 6 and 12 hour collections. The mean gestational age was 30
      weeks and the mean diastolic blood pressure 95 mmHg. Of the patients, 84 had
      proteinuria and 66 had no proteinuria on random urinary dipstick analysis. The
      random urinary dipstick showed a sensitivity of 84%, and a specificity of 61%.
      The urinary dipstick of the hour 6 sample showed a sensitivity of 84.5%, and a
      specificity of 90.1%. Urine analysis of the 6 hour sample showed a sensitivity of
      87.9% and a specificity of 80.4%. Analysis of the 12 hour sample yielded an
      accuracy of approximately 83%. The random urinary dipstick is unreliable in
      screening for proteinuria in hypertensive disorders of pregnancy. A 6 hour
      collection is much more accurate.

PMID- 15511950
TI  - Peripartum ovarian masses.
AB  - The presentation and management of ovarian tumours complicating pregnancy may
      have altered with changes in obstetric practice and developments in diagnostic
      imaging and pathology. A retrospective review of the presentation, management,
      pathological findings and pregnancy outcome of all women whose pregnancies were
      complicated by an ovarian tumour was undertaken. We found 84 cases where ovarian
      masses complicated pregnancy. Thirteen presented in association with an ectopic
      pregnancy. Forty-seven cases were asymptomatic and 29 of these were discovered
      incidentally at caesarean section despite the routine use of ultrasound. Twenty
      two cases were symptomatic, presenting with mass, pain or bleeding. Aspiration
      cytology was helpful in only 53% while histology allowed definitive diagnosis for
      all tumours. Benign cystic teratoma was the most common tumour found. There was
      one tumour of borderline malignancy in this series. Examination of the ovaries at
      the time of caesarean section should be a routine practice since the majority of
      asymptomatic ovarian masses were discovered incidentally and not antenatally,
      having been missed at the time of routine ultrasound. Although differentiation of
      functional from neoplastic lesions can be difficult, most lesions are benign and
      selective conservative management may be considered.

PMID- 15511951
TI  - Hypoglycaemia: a major biochemical complication in eclampsia- its risk factors
      and prognostic value.
AB  - In this two year prospective study, random blood glucose levels were determined
      in 52 eclamptic patients and 38 controls, at the University of Maiduguri Teaching
      Hospital and Specialist Hospitals in Maiduguri, Nigeria. Eclamptic mothers had
      lower glucose levels (mean value = 3.5 mmol/l) than controls (mean value = 6.8
      mmol/l) (P < 0.001). Nineteen eclamptics (36.5%) had hypoglycaemic glucose levels
      (mean value = 2.3 mmol/l). These values returned to normal following intravenous
      administration of dextrose. Risk factors for hypoglycaemia identified in these
      mothers included lack of antenatal care, unsupervised labour at home, labour
      lasting more than 14 hours, obstructed labour, maternal hyperpyrexia, convulsions
      four or more times, deranged liver function especially HELLP syndrome (syndrome
      of haemolysis, elevated liver enzymes and low platelet count), poor energy supply
      in labour, low socio-economic class status and anaemia. A scoring panel derived
      from these risk factors was tested on a separate group of 48 eclamptics and this
      was found to be 96% sensitive. Infusion of 50% dextrose reversed coma in seven of
      eight comatose eclamptics and corrected fetal heart rate irregularities in 13 of
      15 hypoglycaemic eclamptics. Seven of nine patients who suffered from
      posteclamptic psychosis had hypoglycaemic glucose levels. Three mothers with
      hypoglycaemia and HELLP syndrome died after developing hyperglycaemia following
      infusions of 50% and 10% dextrose. Hypoglycaemia should be considered a major
      biochemical complication of eclampsia. Its risk should be identified and its
      treatment be considered in the protocol of the management of eclamptics.

PMID- 15511952
TI  - Gestational diabetes and fetal macrosomia in a multi-ethnic population.
AB  - We set out to examine maternal and neonatal factors surrounding increased
      birthweight in a multi-ethnic population having an increased prevalence of
      diabetes mellitus. Additionally, to document the difference (if any) for such
      neonates in rates of obstetrical operative intervention at delivery where a
      specific diagnosis of maternal gestational diabetes mellitus had been made. This
      was an observational study of unselected mothers giving birth to a neonate of
      4000 g or more. Data for this population concerning the results of antenatal
      screening and diagnostic testing for gestational diabetes mellitus were available
      as a subset of a larger independent and ongoing database. Odds ratios were used
      to compare group attributes subset on ethnic, diabetic screening and diabetic
      diagnostic status. Two ethnic groups showed an increased odds ratio for increased
      birthweight. A diagnosis of diabetes was associated with a twofold increase in
      caesarean section rate, and a significant increase in median birthweight when
      compared with screen positive/ diagnostic negative mothers. A total of 70.4% of
      mothers were overweight or obese while neonatal ponderal index showed a
      dependence on birthweight ( r2 = 0.17). We conclude that ethnic status is an
      important factor in assessing fetal size, as is maternal body mass index. A
      diagnosis of diabetes mellitus confers an increased risk of operative
      intervention at delivery. Our approach to the use of birthweight data requires re
      assessment.

PMID- 15511953
TI  - Maternal height and prior vaginal delivery as predictive factors in trial of
      labour after one caesarean section.
AB  - A retrospective study of 304 booked parturients with one previous lower segment
      caesarean section for non-recurrent indications was carried out with regards to
      factors predicting successful trial of vaginal delivery. The height of the
      parturients, as well as a history of a previous vaginal delivery appeared to be
      predictive factors of success. Seventy per cent of the parturients succeeded in
      delivering vaginally. The mean fetal birthweight was 3362 g for women with
      vaginal delivery, while the mean maternal height was 1.58 m. Of those who needed
      a repeat caesarean section, surgical intervention in 46.15% of the patients was
      indicated by poor cervicometric progress, which might have been appropriately
      addressed by oxytocin augmentation and careful monitoring in labour. Regarding
      prior vaginal delivery, only 31.1% of parturients with a negative history, but
      63.15% with a positive history, had a successful trial. Three cases of ruptured
      uterus were all the result of unacceptable delay in carrying out an abdominal
      delivery when it was clearly indicated. A large prospective study into this
      aspect of obstetric care will probably define additive effects of these two
      definite factors.

PMID- 15511954
TI  - Hepatitis C virus antibodies in pregnant Lebanese women.

PMID- 15511955
TI  - Twenty-five years of the obstetric flying squad in London: time to be grounded?

PMID- 15511956
TI  - The association of squamous cell carcinoma of the vulva and lichen sclerosus:
      implications for management and follow up.
AB  - All cases of biopsy proven squamous cell carcinoma (SCC) of the vulva and of
      lichen sclerosus (LS) presenting to a district general hospital between 1984 and
      1993 were studied. Twenty-eight cases of squamous cell carcinoma of the vulva
      were identified from histological specimens. Histological evidence of LS was
      found in 28.5% and clinical LS in 57%. There was poor correlation between
      clinical and histological findings when SCC arose on a background of LS. A second
      study of all cases of histological LS over the same period showed the incidence
      of SCC in vulval LS to be 7%.

PMID- 15511957
TI  - Sex cord-stromal tumours of the ovary- a 25 year review.
AB  - We present a retrospective study of granulosa cell tumours and thecomas
      encountered in one hospital between 1970 and 1995. There were 17 granulosa cell
      tumours and 17 thecomas. The size of the granulosa cell tumours varied from 3 cm
      to 30 cm in diameter, and no correlation was found between size and evidence of
      invasion. There was also no correlation between either mitotic counts or
      histological pattern and evidence of invasion. Evidence of oestrogen production
      was found in 12/17 granulosa cell tumours (two with endometrial carcinoma and 10
      with endometrial hyperplasia) and in 9/17 of the thecomas (two with endometrial
      carcinoma and seven with endometrial hyperplasia). Thecomas are regarded as
      benign tumours, but granulosa cell tumours are characterised by a long natural
      history with a significant capacity to recur years after an apparent clinical
      cure. It is therefore important that patients with these tumours are followed up
      indefinitely.

PMID- 15511958
TI  - Ovarian function after hysterectomy in an Irish hospital population.
AB  - A group of 52 women following hysterectomy with conservation of one or both
      ovaries was compared with an age-matched control group attending with menstrual
      irregularity/menorrhagia, in terms of proportions of women with postmenopausal
      endocrine profiles, and climacteric symptoms. The mean age for the groups was 42
      years, and the mean interval between hysterectomy and the time of the study was
      3.5 years. Endocrine levels were postmenopausal in six study and two control
      patients, and this difference was not significant. Vasomotor symptoms were a
      complaint of 28 (54%) of the study group and 18 (35%) of the control group, while
      30 (58%) and 18 (35%) respectively had at least two other non-specific symptoms.
      In the absence of prospective studies elucidating the effect of hysterectomy on
      ovarian function, endocrine profiles should be performed in hysterectomised women
      complaining of symptoms.

PMID- 15511959
TI  - The effects of somatostatin in the polycystic ovary syndrome.
AB  - Eighteen obese women (body mass index 30 +/- 6.1 kg/m2) with hyperinsulinaemia
      and with the polycystic ovary syndrome took octreotide at the dose of 100 mug
      s.c. The effect of the drug was assessed on plasma levels of gonadotropins
      luteinising hormone (LH), follicle stimulating hormone (FSH), of insulin, insulin
      like growth factor-1 (IGF-1), androstenedione, testosterone,
      dehydroepiandrosterone sulphate (DHEAS), sex hormone binding globulin (SHBG) and
      insulin-like growth factor-binding protein-3 (IGFBP-3). Octreotide significantly
      reduced LH (31.8%), insulin (52%), IGF-1 (14%), androstenedione (22.6%) and
      testosterone (20%) and increased IGFBP-3 (25%).

PMID- 15511960
TI  - Efficacy of combined ethinyloestradiol (0.035 mg) and cyproterone acetate (2 mg)
      in acne and hirsutism in women with polycystic ovary syndrome.
AB  - The effects of an oral contraceptive containing ethinyloestradiol and cyproterone
      acetate on acne and hirsutism were studied in 82 women with polycystic ovary
      syndrome. The contraceptive was administered for 48 consecutive cycles. Hormone
      and ultrasound evaluations were carried out at baseline and after 48 treatment
      cycles. Acne and hirsutism were evaluated after 18, 24, 36 and 48 treatment
      cycles. Acne resolved in all patients within 24 treatment cycles. Mild and
      moderate hirsutism resolved within 48 treatment cycles. Severe hirsutism
      persisted although it changed to mild or moderate in most of the affected women.

PMID- 15511961
TI  - The Norplant experience at the University Hospital of the West Indies.
AB  - Sixty-eight patients had Norplant inserted between May 1992 and November 1993 as
      part of a pre-introductory study. The main side effect was weight change which
      occurred in 85.3% (58 patients); weight loss occurred in 25.0% (17 patients, one
      patient voiced a complaint) and weight gain occurred in 60.3% (41 patients, 10 of
      whom voiced a complaint). Menstrual problems were the next most frequent side
      effect occurring in 70.4% (48 patients); spotting occurring in 22% (15 patients,
      none of whom complained) and heavy bleeding in 7.3% (five patients, all of whom
      complained). Amenorrhoea occurred in 41.1% (28 patients). Other complaints were
      minor. No pregnancies have been recorded to date. There were no procedural
      complications and all patients were satisfied with the cosmetic appearance. To
      date there have been 36 removals, the majority for menstrual complications.
      Norplant is a safe, effective means of 'reversible sterilisation' which should be
      utilised in family planning programmes throughout the country.

PMID- 15511963
TI  - Thermal balloon endometrial ablation in the treatment of menorrhagia.

PMID- 15511962
TI  - Treatment of Gardnerella vaginalis infection.
AB  - This review of the antibiotic sensitivity pattern of Gardnerella vaginalis
      culture isolates shows that the drugs found sensitive to G. vaginalis cultures
      include the new antimicrobial agents- ciprofloxacin, cefuroxine and ceftazidine,
      and some older antibiotics- ceftriaxone, cloxacillin, erythromycin,
      chloramphenicol and metranidazole. Streptomycin and augmentin showed intermediate
      sensitivity while penicillin, ampicillin, tetracycline and gentamycin exhibited
      resistance to G. vaginalis isolates. Metronidazole is currently the first-line
      drug of choice for the treatment of G. vaginalis and its related infections
      because of its effectiveness not just against G. vaginalis but also against
      anaerobes. It can be administered orally, parenterally and intravaginally as gel
      or sponge. The advantages and drawbacks to the use of these G. vaginalis -
      sensitive drugs, and the place of alternative drugs in the management of G.
      vaginalis - associated infections are discussed.

PMID- 15511964
TI  - Failure of tibolone to control hypoestrogenic symptoms in premenopausal women
      undergoing hysterectomy and bilateral salpingoophorectomy.

PMID- 15511965
TI  - A comparison of hospital stay after laparoscopically assisted, abdominal and
      vaginal hysterectomy.

PMID- 15511966
TI  - Massive midgut volvulus during pregnancy.

PMID- 15511967
TI  - Fatal neonatal subdural haemorrhage following normal vaginal delivery.

PMID- 15511968
TI  - Puerperal ovarian vein thrombosis in a triplet pregnancy complicated by a single
      intrauterine death.

PMID- 15511969
TI  - Pregnancy in a woman with Friedreich's ataxia.

PMID- 15511970
TI  - Idiopathic acute pancreatitis in pregnancy.

PMID- 15511971
TI  - Transfusion with thawed Rh -- D blood of a newborn suffering from haemolytic
      disease due to anti-Rh 17.

PMID- 15511972
TI  - Retroperitoneal leiomyoma presenting after hormone replacement therapy.

PMID- 15511973
TI  - Intrinsic progestogenic effect of tamoxifen on the postmenopausal endometrium.

PMID- 15511974
TI  - A case of concurrent endometrial carcinoma, fallopian tube carcinoma and a benign
      right ovarian serous cystadenoma with tamoxifen therapy.

PMID- 15511975
TI  - Pneumatosis coli: a rare cause of pelvic pain.

PMID- 15511976
TI  - Advanced squamous cell carcinoma developing in a mature cystic teratoma (dermoid)
      of the ovary in a young woman: a diagnostic and therapeutic challenge.

PMID- 15511977
TI  - Torrential rectal haemorrhage in women with genital cancer.

PMID- 15511978
TI  - Emergency cervical cerclage for cervical incompetence.

PMID- 15511981
TI  - British Maternal and Fetal Medicine Society Third Annual Conference. 2 and 3
      April 1998.

PMID- 15511991
TI  - What is really happening to home births?

PMID- 15511992
TI  - The response of the dietary anti-oxidants vitamin E and vitamin C to oxidative
      stress in pre-eclampsia.
AB  - The relationship of oxidants and anti-oxidants in preeclampsia with reference to
      the dietary anti-oxidants vitamin C and vitamin E was investigated. Three groups
      of patients were studied in the third trimester of pregnancy: normotensives ( n =
      32), mild pre-eclamptics ( n = 15) and severe pre-eclamptics ( n = 31) with a
      group of healthy non-pregnant women ( n = 18) serving as a control. Total anti
      oxidant concentration, the concentrations of vitamin C, vitamin E, superoxide
      dismutase, uric acid and the concentration of total oxidant activity, as
      reflected by lipid peroxides, were measured in plasma or red blood cells. Total
      anti-oxidants and vitamin C concentrations were significantly lower in pre
      eclamptic patients than in pregnant controls (P < 0.05), with the concentrations
      in the pregnant controls being significantly lower than in the non-pregnant
      controls (P < 0.05). There was no significant difference in vitamin E
      concentration for all four groups. Superoxide dismutase activity was
      significantly lower in the normal pregnancy group. Lipid peroxides were
      significantly increased in the three pregnant groups (P < 0.05) with no
      differences noted between these groups. The relationship of oxidants to anti
      oxidants in pregnancy and pre-eclampsia is dependent on many factors but balance
      appears to be upset in pre-eclampsia. The reduction in anti-oxidant
      concentrations in pre-eclampsia suggests either a primary deficit or consumption
      of the anti-oxidants measured. Of the dietary anti-oxidants studied, vitamin C
      was most affected in pre-eclampsia.

PMID- 15511993
TI  - The effect of maternal exercise on uterine artery velocimetry waveforms.
AB  - One hundred and two subjects in the second half of pregnancy were subject to an
      acute exercise test lasting 5 minutes on an upright bicycle ergometer. The
      pulsatility index (using Doppler ultrasound) of the right uterine artery was
      analysed before exercise and at 2, 4, 6, 8, 10, 12, 16, 20, 24 and 30 minutes
      after exercise. The mean exercise intensity achieved was 67.2% of sub-maximal
      exercise (range 51-90%). At 2 minutes post-exercise, the mean uterine artery
      pulsatility index was increased from the baseline value, reaching a maximum of
      0.64 at 8 minutes (baseline 0.583). After 8 minutes there was a gradual decrease
      in the pulsatility index, and at 24 and 30 minutes the values were significantly
      lower (P < 0.001 and P < 0.001 respectively). Smokers had significantly higher
      pulsatility index values than non-smokers (P < 0.004). Primigravidae also had
      lower resistance indices compared with multigravidae (P < 0.001). We conclude
      that exercise in the second half of pregnancy appears to cause a transient
      increase in the maternal uterine artery pulsatility index. We also believe that
      at this level of exercise intensity there was no evidence of harmful effects on
      maternal uterine blood flow.

PMID- 15511994
TI  - Blunt-tipped versus sharp-tipped needles: wound morbidity.
AB  - Blunt-tipped needles have previously been shown to reduce needle-stick injury but
      the issue of morbidity had not been addressed. As awareness of the need for
      universal precautions heightens, concerns have been raised about any possible
      morbidity brought about by their use. We present the results of a randomised,
      controlled study which investigated wound morbidity following caesarean section.
      Of the 204 women randomised to closure with sharp or blunt-tipped needles, none
      developed anything other than superficial infection and there were no significant
      differences between the two groups. We conclude that the use of blunt-tipped
      needles does not cause an increase in wound morbidity.

PMID- 15511995
TI  - Vaginal delivery after two or more previous caesarean sections: is trial of
      labour contraindicated?
AB  - A retrospective study was conducted involving 308 patients with previous
      caesarean sections and current singleton pregnancy. All the women delivered at
      the University Teaching Hospital Zaria, after having been in established labour.
      The aim was to determine any significant maternal and fetal risk attributable to
      labour in patients with more than one previous caesarean which may mitigate
      against a trial of vaginal delivery. The study analysis involved a group of
      patients with one previous caesarean section compared with those with more than
      one (multiple) caesarean section who delivered vaginally or abdominally after
      having been in established labour. The results showed that there was no
      significant difference in maternal and perinatal mortality rates and perinatal
      morbidity rates between the two groups. The patients with multiple caesarean
      sections who failed to deliver vaginally had increased rates of postoperative
      pyrexia (18.7%), anaemia (23.4%) and blood transfusion (35.3%). The study showed
      that the risk of fatal outcome related to labour in patients with multiple
      caesarean sections was low and could be eliminated by careful patient selection
      and close intrapartum care. A positive review of policy towards a trial of
      vaginal delivery in multiple caesarean sections is therefore advocated in view of
      the advances in patient management in contemporary obstetric care. The gains in
      terms of patient compliance towards hospital care and supervised delivery will be
      considerable. A multicentre, prospective case-controlled trial will clearly
      define the risks attributable to this policy change.

PMID- 15511996
TI  - Epidural analgesia for low risk labour determines the rate of instrumental
      deliveries but not that of caesarean sections.
AB  - We analysed retrospectively the link between the incidence of epidural analgesia
      and the frequency distribution of instrumental delivery, caesarean section,
      labour induction and parity in a selected group of women with a low risk labour
      profile in all (85) obstetric units in Flanders (Northern Belgium). A group of
      104 932 women with presumed low risk labour profile was subjected to analysis.
      The main outcome measures were the incidence of obstetric intervention in each
      obstetric unit in relation to the extent of their use of epidural analgesia.
      There was a wide variation in the rate of epidural analgesia (3-75%), labour
      induction 'for convenience' (4-48%) and instrumental delivery (4-50%) among the
      Flemish obstetric units. The incidence of instrumental delivery in a given unit
      was greatly influenced by the rate of epidural analgesia and labour induction for
      convenience (P < 0.001). However, the incidence of caesarean section in a given
      unit was not determined by either the rates of epidural, labour induction,
      attempted instrumental delivery or the size of the unit.

PMID- 15511997
TI  - Effect of mode of delivery on perinatal results in singleton breech presentation
      weighing >/= 1500 g.
AB  - The object of this retrospective study was to evaluate the mode of delivery and
      perinatal outcome of singleton fetuses with breech presentation weighing >/= 1500
      g. Consecutive cases of all singleton pregnancies at the Princess Badeea Teaching
      Hospital in North Jordan in the years 1994 and 1995 were compared for crude and
      corrected perinatal mortality and effect of mode of delivery by weight after
      correction for non-preventable causes. There were no differences in the 1 and 5
      minutes Apgar scores and corrected perinatal mortality between those delivered
      vaginally and abdominally. It is concluded that poor perinatal outcome are
      primarily related to factors other than breech presentation. The mode of delivery
      for infants weighing >/= 1500 g does not influence neonatal outcome and therefore
      caesarean section for breech presentation in this group is not justified.

PMID- 15511998
TI  - A clinical study to evaluate the usefulness of the MAST test in diagnosing pre
      labour rupture of membranes.
AB  - An open study was performed to evaluate the efficiency of insulin-like growth
      factor binding protein-1 as a marker for the detection of pre-labour rupture of
      membranes and to assess whether it aided the subsequent clinical management. One
      hundred women between 24 and 42 weeks' gestation with a history suggestive of pre
      labour rupture of membranes were studied. There were 11 false positive and no
      false negative results and the sensitivity and specificity were 100% and 89%
      respectively. The presence of infection, blood or semen did not interfere with
      the accuracy of the results.

PMID- 15511999
TI  - Obstetric deaths in Trinidad.
AB  - We determined the causal pathways of pregnancy-related deaths over a 16-year
      period. Pregnancy-induced hypertension was the chief contributor to our high
      maternal mortality rate of 36.9 per 100 000 births. Anaesthetic-related deaths
      were due to a combination of Mendelson's syndrome and faulty intubation
      technique. An improvement in the health-management system to identify high-risk
      mothers who need intensive emergency care and the availability of experienced
      personnel for obstetric anaesthesia appear to be indispensable requirements for
      reducing and minimising adverse maternal outcome in Trinidad.

PMID- 15512000
TI  - Pregnancy outcome in the elderly primigravidae.
AB  - We assessed the effect of advancing maternal age ( 35 years) on the outcome of
      pregnancy in first births among 50 elderly primigravidae compared with a control
      group of 50 younger primigravidae (20-29 years) at the University College
      Hospital Ibadan from 1 January 1988 to 31 December 1992. Most of the elderly
      primigravidae were professionals and the majority of them (68%) had involuntary
      infertility. Frequent hospital admissions, preterm delivery, low birth weights
      and very high caesarean section rates were the major problems highlighted in the
      elderly primigravidae, while anaemia was more frequent in the younger
      primigravidae. Unnecessary caesarean sections on the excuse of 'precious' baby in
      the elderly primigravidae should be discouraged bearing in mind its medico-social
      implications. It is concluded that although the elderly primigravidae may have
      higher rates of complications of pregnancy, delivery and neonatal deaths their
      overall risk of referral to special care baby unit is not appreciably increased.

PMID- 15512001
TI  - The localisation of copper/zinc superoxide dismutase in human normal term
      placenta by an immunofluorescence technique.
AB  - The antioxidant enzyme copper and zinc containing superoxide dismutase (Cu/Zn
      SOD) was localised in normal human term placenta to the syncytial trophoblast,
      using an immunofluorescence technique. Possible physiological roles of Cu/Zn SOD
      in the human placenta are discussed.

PMID- 15512002
TI  - Mode of delivery and perinatal results of the breech first twin.
AB  - To evaluate the safety of vaginal delivery for breech first twin we reviewed
      retrospectively and compared the perinatal outcome of breech first twin: 42
      delivered vaginally and 87 delivered abdominally. Vaginal delivery was allowed
      under the same criteria for singleton breech presentation. Both groups had
      similar maternal and neonatal characteristics. Intergroup differences in
      perinatal outcome, as measured by Apgar score, and mortality cases, were not
      significant. Our results showed that vaginal delivery is a safe mode of delivery
      and this route is not associated with higher mortality and morbidity.

PMID- 15512003
TI  - A follow-up of repair of ruptured uterus in Ethiopia.
AB  - The uterus was conserved and repaired in 238 of 245 mothers admitted with
      ruptured uterus to a rural hospital in Ethiopia between 1991 and 1995. The
      patients have been followed for intervals varying from 6 years and 3 months to 1
      year and 11 months since treatment of their rupture. One hundred and eleven
      mothers have given birth to 117 healthy babies. All mothers are well. Repair of
      uterine rupture is medically safe and culturally acceptable to the population
      served, provided the mothers are willing to spend the latter months of subsequent
      pregnancies in the maternity waiting area.

PMID- 15512004
TI  - The Pipelle endometrial suction curette: how useful is it in clinical practice?
AB  - The Pipelle endometrial sampler is gaining popularity as an alternative to formal
      dilatation and curettage (D&C). This study demonstrates that the Pipelle reduces
      the number of D&Cs required to assess the endometrium by 65%. This has
      significant benefits in terms of patient safety and cost. If an inadequate sample
      is obtained, which occurs most commonly in the postmenopausal patient, there may
      be a temptation to ascribe this to the presence of an atrophic endometrium. This
      study, however, finds a significant chance of an underlying carcinoma in these
      cases. Thus whereas the Pipelle sampler has clinical usefulness when a sample
      sufficient for histological analysis is obtained, an equivocal result must lead
      to further investigation.

PMID- 15512005
TI  - A single transurethral Macroplastique injection as primary treatment for stress
      incontinence in women.
AB  - The clinical records of 102 women were analysed to estimate the success rate of a
      single transurethral Macroplastique (Uroplasty BV, Netherlands) injection for the
      treatment of stress incontinence. We then compared the results of those who had
      had the injection as primary treatment (71/102) with those women who had
      undergone previous failed incontinence surgery (31/102). The overall success rate
      was 68% following a single injection of Macroplastique at a mean follow-up period
      of 3.2 months; the success rate was obtained by including all patients who were
      either cured or markedly improved requiring no further intervention. The success
      rate of those who had had previous surgery was 71% and for the primary treatment
      group it was 66%. This difference was not statistically significant. These
      results suggest a potential role of Macroplastique transurethral injection as
      primary treatment for genuine stress incontinence in women.

PMID- 15512006
TI  - The modified rectus fascial sling for the treatment of genuine stress
      incontinence.
AB  - We aimed to assess the results of the modified rectus fascial sling for the
      treatment of genuine stress incontinence (GSI), using an observational study of
      patients at a South Wales Teaching Hospital. Seventy-three patients with proven
      GSI underwent a modified rectus fascial sling. Thirty-seven also had a
      significant urge component to their symptoms though only two had demonstrable
      detrusor instability. Fifty-one had undergone previous incontinence surgery. All
      had pre-operative videourodynamics and 50 agreed to follow up urodynamics. Of
      these who had undergone previous surgery 48 (94%) were subjectively dry, though
      four (8%) still demonstrated GSI on videourodynamics. There were no failures in
      the previously unoperated group. Three require long-term intermittent self
      catheterisation and three others catheterise occasionally. Overall, 29 patients
      (78%) were improved or cured of their urge component but three were worse, with
      urge incontinence. From our data, it seems that the modified rectus fascial sling
      is superior to standard techniques for GSI especially in patients who have
      undergone previous surgery. However loosely the sling is placed, a small but
      significant group are obstructed by the procedure, and may require self
      catheterisation.

PMID- 15512007
TI  - A study of the prevalence of hydrogen peroxide generating Lactobacilli in
      bacterial vaginosis: the determination of H2O2 concentrations generated, in vitro
      , by isolated strains and the levels found in vaginal secretions of women with
      and without infection.
AB  - The concentration of hydrogen peroxide in the vaginal secretions of normal women
      were compared with levels found in women infected with bacterial vaginosis (BV).
      The mean concentration found in 90 normal samples was 0.171 microg per ml,
      whereas in women with BV, the mean level was 0.04 microg per ml (P < 0.001). In
      vitro culture experiments using TMB agar showed that in normal women, 75% of
      Lactobacillus strains produced H2O2 and 25% did not, whereas in women 'infected'
      with BV. 14% of the isolates produced H2O2 and 86% did not (P < 0.001).
      Quantitative culture tests showed that both anaerobic and facultative strains of
      Lactobacilli isolated from normal women generated significantly higher levels of
      H2O2 than strains cultured from women with BV. Anaerobic strains isolated from
      normal women produced a mean level of 6.8 microg per ml, compared with the mean
      level of 1.4 microg per ml from women with BV. Facultative strains from normal
      women produced mean levels of 18.3 microg per ml compared with 2.4 microg per ml
      produced by strains from BV-infected women, which had been incubated under the
      same conditions (P < 0.001). There results indicate that Lactobacilli which
      produce H2O2 probably have a significant role in protecting the vaginal ecosystem
      from BV infection.

PMID- 15512008
TI  - Why do women volunteer to participate in clinical studies?
AB  - The purpose of this study was to determine why young women volunteer to
      participate in clinical studies. Questionnaires were sent to 126 healthy fertile
      women, who during 1 year had undertaken contraceptive pill trials in the
      Reproductive Medicine Unit, of the University Hospital of South Manchester. An
      85% response rate was obtained. Most of these women worked, were married and had
      children. Study recruitment was most effective by 'word of mouth', posters within
      the hospital not attracting many volunteers. They volunteered to take part
      because of the perceived financial gain from 'reasonable expenses' payable. Only
      11.2% expressed a desire to assist in medical research or have their own health
      checked. The sex of the study investigator was not crucial to their
      participation; 94.4% were willing to participate in future pill trials.
      Therefore, when planning a clinical study requiring healthy volunteers,
      reasonable expenses are an essential compensation to aid the recruitment process.

PMID- 15512009
TI  - Elective hysterectomy at Ilorin, Nigeria-4 year review.
AB  - This study reviews all cases of hysterectomy performed at the University of
      Ilorin Teaching Hospital, Ilorin over a 4-year period between 1 April 1984 and 31
      March 1988. There were 155 elective hysterectomies out of 1828 elective major
      gynaecological procedures with a prevalence rate of 8.5%. An analysis of 128 case
      notes available for review revealed that 100 (78%) of the patients had total
      abdominal hysterectomy (TAH) while the remaining 28 (22%) had vaginal
      hysterectomy (VH). Uterine fibroids were the leading indication for TAH while all
      the VH were for utero-vaginal prolapse. In spite of routine use of prophylactic
      antibiotics, febrile morbidity and wound sepsis were among the leading
      complications. Unnecessary blood transfusions were frequent. Mortality rate in
      elective hysterectomy was 0.78%.

PMID- 15512010
TI  - The use of hormone assays and transvaginal ultrasound measurement of endometrial
      thickness in the management of recurrent postmenopausal bleeding.
AB  - In patients presenting with postmenopausal bleeding, once an initial hysteroscopy
      and curettage has excluded uterine pathology there is no need to repeat the
      procedure unless there are very strong grounds for suspecting an occult
      carcinoma. By carefully tracking oestrogen levels subsequently, it is possible to
      predict if and when recurrent episodes of bleeding will occur. A transvaginal
      ultrasound measured endometrial thickness of less than 5 mm provides additional
      reassurance that there is no sinister underlying pathology.

PMID- 15512011
TI  - Intravenous immune globulins in Guillain-Barre syndrome in pregnancy.

PMID- 15512012
TI  - Entrapped after-coming head at caesarean breech delivery.

PMID- 15512013
TI  - Removal of cervical suture to stop preterm labour.

PMID- 15512014
TI  - Postpartum superior sagittal sinus thrombosis.

PMID- 15512015
TI  - Severe hyperlipidaemia in pregnancy related to the use of low-molecular-weight
      heparin-enoxaparin sodium (clexane).

PMID- 15512016
TI  - Recurrent Potter's syndrome in a consanguineous marriage.

PMID- 15512017
TI  - Diagnosis and treatment of ruptured splenic artery aneurysm in pregnancy.

PMID- 15512018
TI  - Spontaneous iliac artery dissection in a healthy postpartum woman.

PMID- 15512019
TI  - Dyspareunia due to osteochondroma of the pubic ramus.

PMID- 15512020
TI  - Ovarian hilus cell tumours.

PMID- 15512021
TI  - Use of temporary filters in the vena cava.

PMID- 15512022
TI  - Annual meeting of the Northern Obstetrical and Gynaecological Society,
      Postgraduate Centre, Raigmore Hospital, Inverness, 9 May 1997.

PMID- 15512025
TI  - Cerebral pathology in the pre-term infant and associated peripartum metabolic
      acidosis.
AB  - In a prospective study of 217 infants who were delivered before 37 weeks'
      gestation and in whom serial cranial ultrasound scans were performed to identify
      cerebral pathology, multivariate analysis, including a wide range of peripartum
      and neonatal variables, demonstrated that metabolic acidosis present at delivery
      and persisting during the early neonatal period was associated with the
      development of cerebral pathology in these infants. These findings support the
      hypothesis that the condition at birth of the preterm infant as assessed by
      acid/base balance, which reflects events occurring during labour and delivery, is
      an important factor in the subsequent development of cerebral pathology. In
      addition, the data support the view that obstetric policies aimed at avoiding
      metabolic acidosis at birth are likely to be of benefit to the pre-term infant.

PMID- 15512026
TI  - The influence of maternal request on the elective caesarean section rate.
AB  - At a time when there is much criticism of increasing caesarean section rates, as
      well as an increased emphasis on involving the patient in decisions regarding her
      care, we decided to assess the effect of maternal request on the elective
      caesarean section rate. The study was a prospective patient interview and case
      note review, set at a District General Hospital in Watford, Hertfordshire over a
      1-year period. Eligible patients included all women undergoing elective caesarean
      section, with the main outcome measure being the number of elective caesarean
      sections performed without obstetric contraindication to vaginal delivery. Out of
      3025 deliveries, 570 (18.8%) were delivered by caesarean section, 276 (9.1%)
      electively and 293 (9.7%) as an emergency procedure. Of the elective procedures
      (18.2% of the total number of operations), 38% were performed because of maternal
      request. We conclude that maternal request is a significant factor in the rise in
      caesarean section rate.

PMID- 15512027
TI  - What is the value of hospitalisation in antepartum haemorrhage of uncertain
      origin?
AB  - This retrospective analysis was designed to determine the need for
      hospitalisation in cases of antepartum haemorrhage of uncertain origin (AUO). All
      the cases of AUO that presented at the Chelsea and Westminster Hospital from
      February 1993 to December 1995 were analysed. AUO accounted for 72% of cases of
      antepartum, haemorrhage Hospitalisation of the cases of AUO conferred no benefit
      in terms of gestation at delivery, birth weight centile, 5 minutes Apgar score
      and recurrent haemorrhage. Also, the duration of stay in hospital was not
      significantly related to the gestation at delivery ( r = 0.084, P > 0.05), the
      birth weight centile ( r = 0.032, P > 0.05) or the Apgar score at 5 minutes ( r =
      0.062, P > 0.05). We conclude that it is not necessary to hospitalise women with
      AUO in the absence of heavy or repeated bleeding, evidence of fetal or maternal
      compromise on any suggestion of the onset of labour.

PMID- 15512028
TI  - Prevention of hypertensive disorders of pregnancy.
AB  - A prospective randomised clinical trial comprising 510 pregnant patients was
      performed to determine whether supplementation with calcium, low-dose aspirin or
      a combination of calcium and low-dose aspirin can lower the incidence of
      hypertension in pregnancy. Greatest benefits were obtained with calcium.
      Perinatal mortality was lowest in the aspirin group.

PMID- 15512029
TI  - Breech presentation after 34 weeks-a meta-analysis of corrected perinatal
      mortality/morbidity according to the method of delivery.
AB  - We conducted a meta-analysis of the mortality and morbidity of the breech
      presentation according to the method of delivery. Using the term 'breech', we
      used the Medline data base to search the English and French-language literature
      from 1978 to July 1995. Twenty-two studies (7239 deliveries) were found and
      analysed. The meta-analysis concerning perinatal mortality did not reveal a
      significant increased risk, when vaginal deliveries were compared with those
      delivered by a caesarean section (odds ratio: 1.90; confidence interval: 0.59
      8.22) or when vaginal deliveries were compared with those done by planned
      caesarean section (odds ratio: 4.95; confidence interval: 0.44-80.06). The
      neonatal morbidity showed an increased risk with vaginal delivery. It is
      concluded that the practice of resorting to caesarean section for every breech
      presentation at term does not seem defensible.

PMID- 15512030
TI  - Is the second-born twin at high risk?
AB  - We set out to compare the outcome of the second born twin with that of the first
      twin to determine if any differences could be improved. We reviewed
      retrospectively twin deliveries from 15 April 1994 to 14 April 1996. We excluded
      from analysis twins weighing < 500 g, where either twin had lethal malformation,
      and where either twin was dead before the onset of labour. After these exclusions
      246 twin pairs remained in the study. We compared perinatal mortality, and 5
      minutes Apgar scores for both twins. Perinatal mortality was similar for both
      twins as was the 5 minutes Apgar scores. Twins < 1500 g appear at special risk.
      The mode of delivery has no influence on the perinatal outcome of both twins. It
      is concluded that the second born twin may not be at increased risk of
      complications compared with the first born twin. Caesarean delivery will not
      improve this outcome.

PMID- 15512031
TI  - Great grand multiparity: is it a risk?
AB  - We wished to compare antenatal and intrapartum complications among women
      delivering for the 10th or subsequent time and to compare them with women of
      lower parity (para 2-5). The records of 154 women of great grand parity (para >/=
      10) were reviewed and compared with 308 women (para 2-5) delivered during the
      same period. Antepartum as well as intrapartum complications were compared. All
      the women delivered between 16 April 1994 and 15 January 1995. Great grand
      multiparous women were, not surprisingly, older. The incidence of diabetes
      millitus, chronic hypertension, preterm labour are similar to those with low
      parity while they have higher incidence of pre-eclampsia (7.1% vs. 2.6%) and
      intrauterine fetal death (5.2 vs. 1.3%) P < 0.04. There were no differences in
      the incidence of placental abruption, placenta previa, malpresentation and
      postpartum haemorrhage between the two groups. Great grand multipara had a higher
      incidence of macrosomia (7% vs. 2%) and operative delivery (20.6% vs. 11.4%) P <
      0.02. Great grand multiparous woman are at some increased risk of having severe
      pre-eclampsia, intrauterine fetal death macrosomia and subsequently operative
      delivery with its associated risk of maternal mortality and morbidity.

PMID- 15512032
TI  - Maternal mortality in Maiduguri, Nigeria.
AB  - Maternal mortality is an index of the standard of antenatal care in a given
      environment. In developed countries the level of antenatal care has risen to an
      extent that maternal mortality has virtually disappeared (Nylander and Adekunle,
      1990). This is in sharp contrast with the situation in developing countries like
      Nigeria where maternal mortality is still deplorably high. According to the World
      Health Organization, only 29-36% of deliveries in Africa are attended to by
      trained health personnel (World Health Organization, 1985). Therefore the
      mortality rates reported from most developing countries may be just the tip of
      the iceberg. Another disturbing dimension to the problem of maternal deaths in
      developing countries is the fact that most of the deaths are due to causes that
      can be prevented by the provision of essential obstetric care. Nearly a decade
      after the launching of the international safe motherhood initiative the tragedy
      of maternal deaths remains unmitigated in most developing countries such as
      Nigeria. The purpose of this study is to evaluate the causes of maternal deaths
      in two tertiary level hospitals in Maiduguri, north-eastern Nigeria and to
      identify ways of reversing the trend.

PMID- 15512033
TI  - The influence of medroxyprogesterone acetate on the effects of transdermal
      oestradiol replacement therapy on plasma lipids.
AB  - A prospective study was carried out on 82 healthy menopausal women to determine
      whether or not there is an attenuation of the cardioprotective effects of
      continuous transdermal oestradiol on plasma lipid and lipoprotein concentrations
      with the use of sequential oral medroxyprogesterone acetate. Group 1 comprised 51
      hysterectomised women on transdermal oestradiol (50 microg daily). Group 2
      included 31 women with an intact uterus on oestradiol (50 microg daily) and
      medroxyprogesterone acetate (10 mg daily for the first 12 days of each calendar
      month). Women maintained on 50 microg throughout 6 months (group 1: n = 29; group
      2: n = 20) were reviewed for changes in plasma lipids and lipoproteins at the end
      of 6 months (group 1), and in the combined phase of treatment in the seventh
      month (group 2). In group 1, there was a reduction in the concentrations of total
      cholesterol (- 6.3%, P = 0.004) and LDL-cholesterol (- 6.1%, P = 0.05). In group
      2, there were no significant changes in total cholesterol (- 4.8%, P = 0.23) and
      LDL-cholesterol (- 5.8%, P = 0.30). HDL-cholesterol levels did not change
      significantly with unopposed oestradiol (+ 3.8%, P = 0.30), or with additional
      medroxyprogesterone acetate (0%, P = 0.94). Serum triglyceride concentrations
      decreased significantly in both the groups (- 14.3%, P = 0.001, and- 12.8%, P =
      0.006, respectively). There were no statistically significant differences in the
      changes in the respective plasma lipid parameters on comparing the two treatment
      groups (P > 0.4 for all comparisons, Student's t -tests). The plasma lipid and
      lipoprotein profile encountered at the end of 6 months, was also generally
      maintained in 24 women (group 1: n = 13; group 2: n = 11) who completed 1 year of
      the study. Transdermal oestradiol may be of particular clinical benefit for women
      with hypertriglyceridaemia. Medroxyprogesterone acetate did not exert a
      significantly adverse influence on plasma lipid and lipoprotein concentrations.

PMID- 15512034
TI  - Amielle vaginal trainers-a patient evaluation.
AB  - Ten consecutive patients presenting to a gynaecology clinic with a principal
      diagnosis of secondary vaginismus and superficial dyspareunia were given a set of
      Amielle vaginal trainers and instructed in their use. They were subsequently sent
      a questionnaire asking for their evaluation of the efficacy of the trainers. Nine
      patients (90%) reported a substantial improvement or complete cure of their
      symptoms. All patients who used the vaginal trainers gave favourable reports on
      the physical characteristics of the product. Amielle vaginal trainers seem both
      effective in the treatment of vaginismus and superficial dyspareunia and
      aesthetically acceptable to majority of patients.

PMID- 15512035
TI  - Evaluation of a one-stop clinic for the rapid assessment of post-menopausal
      bleeding.
AB  - In this study, we evaluated the management of postmenopausal bleeding at our one
      stop clinic where the first line investigations were a transvaginal ultrasound
      scan and a pipelle endometrial biopsy. The records of 212 women seen in this
      clinic in 1994 were reviewed. One hundred and forty-four women (67.9%) were
      evaluated and reassured in one visit. The mean waiting period following referral
      to the clinic by the general practitioner was 36 days (range 6-157 days), and
      only 45 women (21%) required a hysteroscopy. The commonest diagnosis made was
      endometrial atrophy or no significant endometrial pathology (130 women (61.3%).
      Endometrial cancer was diagnosed in 12 women (5.6%), and one case of previously
      unsuspected ovarian cancer was detected. Our findings show that most women with
      post-menopausal bleeding can be assessed in one visit, and hysteroscopy is not
      always necessary in the initial assessment of this complaint.

PMID- 15512036
TI  - Knowledge and use of emergency contraception amongst Nigerian undergraduates.
AB  - Randomly selected Nigerian female undergraduates were surveyed to determine their
      knowledge and use of emergency contraception. The majority of the students were
      nullipara (96%) and single (92%). Although awareness of the existence of
      emergency contraception was high (84%), only 31% of the respondents were
      correctly aware of the time limit for using emergency contraception. There is
      need to educate all women including the general population about emergency
      contraception and the correct timing of its use.

PMID- 15512037
TI  - Determinants of utilisation of cervical cancer screening facility in a low socio
      economic setting in Nigeria.
AB  - A prospective randomised structured questionnaire survey of 254 women in the low
      socio-economic class attending the general outpatient clinic at the University
      College Hospital (UCH), Ibadan revealed a high level of ignorance concerning
      cervical cancer prevention programmes. Only 3.5% of subjects have heard of a
      Papanicolaou smear and only 1.2% have had the test prior to this study. Peers
      (36%) were the most common source of information on cervical smears. The majority
      (84.6%) of the women were willing to be screened, however only 5.1% of those
      willing (4.3% of the women studied) actually reported for the test. Twenty-two
      percent (219) had high knowledge about cervical smears while moderate and poor
      knowledge were demonstrated in 33% respectively. Eleven per cent had no knowledge
      whatever. No significant association was found between the knowledge score on
      Papanicolaou smear and other variables. The cost of the test appeared to have
      prevented many of the women from having the test. It is recommended that more
      efforts need to be put into health education of women stressing the importance of
      the test and its availability.

PMID- 15512038
TI  - Pregnancy trends after abortion.
AB  - A series of women who aborted their pregnancies at King Khalid University
      Hospital (KKUH), Riyadh, Saudi Arabia, over a period of 12 months (1 January 1992
      to 3 December 1992), were followed up for 6-48 months afterwards to examine their
      pregnancy trends. Descriptive statistics for data presentation with Kaplan-Meier
      survivorship function estimates time from abortion to the next pregnancy and Cox
      proportional hazard regression analysis were used to identify prognostic factors.
      Eighty-one per cent of the women achieved pregnancy over a 4-year follow-up. The
      median time to pregnancy was 7.6 months, with a 95% confidence interval of 6.4
      10.0 months. Age and nationality were found to be significant prognostic factors
      related to time to achieve a pregnancy. Furthermore, the outcome of the
      subsequent pregnancy was found to be statistically related to the number of
      previous abortions. There is a high chance of fertility after an abortion, with
      75.2% of these occurring within the first 12 months of the post-abortion follow
      up period and dwindling to only 4.1% by the end of 36 months. Using multivariate
      regression analysis, only age seemed to be an important determinant factor.

PMID- 15512039
TI  - Laparoscopic and microbiological features of acute salpingitis in developing
      countries.
AB  - One hundred and twenty-four out of 198 consecutive women who underwent diagnostic
      lasparoscopy for clinical symptoms and signs of acute salpingitis at the
      University College Hospital, Ibadan, Nigeria had acute salpingitis. These were
      slightly younger than those without acute salpingitis, otherwise there were no
      differences in the sociodemographic characteristics of the two groups. Urinary
      and gastrointestinal symptoms, abnormal vaginal discharge, fever (> 38 degrees C)
      and sexually transmitted organisms were significantly more in women with acute
      salpingitis. Ninety-five per cent of the Neisseria gonorrhoea cultured were of
      the PPNG strain. Pelvic adhesions were present in 69.4% of the women with acute
      salpingitis. Forty-one per cent of the women had tubal occlusion. It was
      concluded that laparoscopy rather than clinical findings alone would determine
      the severity of acute salpingitis. This should be performed along with culture of
      genital discharges and peritoneal fluid for optimum management. The use of a
      single dose broad spectrum antibiotics active against both PPNG and non-PPNG
      strains, and chlamydial infections is advocated for treatment in developing
      countries.

PMID- 15512040
TI  - Management of ectopic pregnancy by laparotomy and subsequent fertility.

PMID- 15512041
TI  - Unilateral ovarian diathermy prior to successful in vitro fertilisation: a
      strategy to prevent recurrence of ovarian hyperstimulation syndrome?

PMID- 15512042
TI  - Active management of acute hyperlipidaemic pancreatitis in pregnancy.

PMID- 15512043
TI  - Haemorrhage from umbilical cord varices-an unusual cause of abnormal
      cardiotocography.

PMID- 15512044
TI  - Protein S deficiency and factor V Leiden gene in pregnancy.

PMID- 15512045
TI  - Acquired postpartum factor VIII deficiency: a cause of severe postpartum
      complications.

PMID- 15512046
TI  - Protein C deficiency and stroke in pregnancy.

PMID- 15512047
TI  - Rupture of the uterus with misoprostol (prostaglandin El) used for induction of
      labour.

PMID- 15512048
TI  - Toxic shock syndrome following minor surgery in pregnancy resulting in premature
      labour and subsequent neonatal death.

PMID- 15512049
TI  - Fever in a pregnant woman with common variable immunodeficiency.

PMID- 15512050
TI  - Early presentation and spontaneous resolution of hydrops fetalis, secondary to
      parvovirus B19 infection.

PMID- 15512052
TI  - An unusual cause of right iliac fossa pain for the gynaecologist: benign
      fallopian tube teratoma.

PMID- 15512051
TI  - Vitamin B12 deficiency and IVF.

PMID- 15512053
TI  - Intestinal-ovarian fistula associated with endometriosis.

PMID- 15512054
TI  - Complete response of persistent trophoblastic disease to methotrexate following
      laparoscopic linear salpingostomy.

PMID- 15512055
TI  - Female adnexal tumour of probable Wolffian origin.

PMID- 15512056
TI  - Chronic non-puerperal inversion of the uterus.

PMID- 15512057
TI  - Unilateral autoamputation of the fallopian tube.

PMID- 15512058
TI  - Splenic aneurysm rupture mimicking a pulmonary embolism.

PMID- 15512059
TI  - Anaerobic vaginosis and premalignant disease of the cervix.

PMID- 15512061
TI  - The 1995 pill scare and its aftermath: lessons learnt.

PMID- 15512062
TI  - Risk factors for preeclampsia-eclampsia among Zimbabwean women: recurrence risk
      and familial tendency towards hypertension.
AB  - We sought to estimate the risk of recurrence of preeclampsia-eclampsia among
      Zimbabwean women. Additionally, we sought to assess the extent to which family
      history of pregnancy-induced or chronic hypertension was predicative of the risk
      of developing preeclampsia-eclampsia. This hospital based case-control study was
      conducted at Harare Maternity Hospital, Harare Zimbabwe during the period June
      1995 to April 1996. Study participants were 200 women with preeclampsia or
      eclampsia and 200 normotensive pregnant women serving as controls. Logistic
      regression procedures were used to estimate odds ratios (ORs) and 95% confidence
      intervals (CIs). Among multiparous women, a history of any pregnancy-induced
      hypertension was associated with a 10.5-fold increase in risk of preeclampsia
      eclampsia in a subsequent pregnancy (95% CI 4.7-23.5). Women who reported that
      their mother or sisters experienced pregnancy-induced hypertension were found to
      be at an increased risk of preeclampsia-eclampsia (OR = 2.3 and 2.6,
      respectively). A 2.3-fold excess risk of preeclampsia-eclampsia was associated
      with paturients' maternal history of chronic hypertension (95% CI 1.3-3.6). The
      corresponding relative risk of preeclampsia-eclampsia for women reporting to have
      a sister with chronic hypertension was 2.6 (95% CI 1.2-5.3). Zimbabwean women,
      like North American and European women, are at increased risk for the recurrence
      of preeclampsia-eclampsia. Findings from our study and those of others suggest a
      possible genetic component involved in the multifactorial aetiology of
      preeclampsia-eclampsia. The information provided here should be useful to
      clinicians involved in the management of patients with a prior history or family
      history of hypertension.

PMID- 15512063
TI  - Management of meconium-stained neonates.
AB  - We examined the use of a new scoring system for the meconium-stained infant,
      which was designed to help the neonatologist decide on the appropriate
      therapeutic approach in the delivery room. Eighty meconium-stained infants were
      scored for: presence of fetal distress; meconium quality; performance of
      nasopharyngeal suctioning before the first breath and clinical condition in the
      first minute of life. Management consisted of gentle oropharyngeal suctioning or
      intubation and tracheal suctioning. Clinical outcome was compared with that of
      100 meconium-stained infants born a year earlier. All babies in the control group
      underwent laryngoscopy and 30% were subsequently intubated. Universal
      laryngoscopy was not performed in the study group, and only 22.5% of these
      infants were intubated. The clinical outcome of the studied babies was identical
      to that of the newborns treated by the standard procedure. The use of the
      meconium intubation score eliminated the need for universal delivery room
      laryngoscopy for meconium-stained infants and significantly reduced the number of
      intubations performed.

PMID- 15512064
TI  - Perinatal factors influencing survival in extremely low-birthweight infants.
AB  - The majority of deaths in normally formed infants occur in extremely low birth
      weight infants (< 1000 g). Survival rates for these infants have improved greatly
      but still vary from centre to centre and accurate local outcome figures are
      important for counselling parents and upholding standards of care. In the Rotunda
      Hospital, Dublin, over the 6 year period from 1 January 1990 to 31 December 1995,
      there were 34 474 deliveries over 500 g birthweight. One hundred and twenty-six
      of these were normally formed infants between 500 g and 999 g. Our objective was
      to analyse the factors influencing survival in these extremely low birthweight
      (ELBW) infants. Overall survival in the group was 63%. The most significant
      factors influencing survival to 28 days were gestation and birthweight. Survival
      increased from 33% at 24 weeks to 100% at 28 weeks' gestation and from 29% at 500
      599 g to 87% at 900-999 g birthweight. Having controlled for gestational age,
      none of the following variables had a significant effect on survival: year of
      birth; gender; multiple pregnancy; 1-minute Apgar score; maternal age; parity;
      use of antenatal steroids; a history of antepartum haemorrhage, pre-eclamptic
      toxaemia or prolonged rupture of membranes. A 5-min Apgar score > 5 increased the
      chance of survival by 3.97 (95% CI: 1.46- 10). Both mode of delivery and
      incidence of chorioamnionitis had an influence on survival which varied according
      to the gestational age. A larger cohort of survivors would illustrate the effect
      of these variables more clearly.

PMID- 15512065
TI  - A population study of face and brow presentation.
AB  - This was a retrospective review of the experience of face and brow presentation
      deliveries in South Glamorgan between 1990 and 1996. The incidence of face and
      brow presentation was 1 in 994 and 1 in 755 deliveries respectively (no cases of
      cranial vault anomalies in this series). There was a higher incidence of
      prematurity and very low birthweight among infants delivered by face presentation
      and higher incidence of postmaturity among those delivered by brow when compared
      with the vertex population in the same period. Over half of malpresentations were
      diagnosed in the second stage. Most fetuses presenting by the brow were delivered
      by caesarean section and 56% of fetuses presenting by face presentation achieved
      a vaginal delivery. The reported incidence of these forms of deflexed cephalic
      attitudes has gradually changed over the last century especially over the past
      decade when the incidence of face is no longer more common than brow
      presentation.

PMID- 15512066
TI  - Intravaginal naproxen in preterm labour: a preliminary study.
AB  - In a preliminary study, the possibility that local inhibition of postaglandin
      formation may inhibit preterm labour was examined. An intravaginal cyclo
      oxygenase inhibitor, naproxen sodium, 500 mg was used in cases of preterm labour.
      The gestational ages of the patients were between 27 and 34 weeks, and they
      included a triplet pregnancy unresponsive to beta-sympathomimetic therapy.
      Treatment with intravaginal naproxen sodium was associated with prolongation of
      pregnancy for more than 6 days in five out of seven patients. No untoward fetal
      or maternal side-effects were detected.

PMID- 15512067
TI  - Scleroderma in pregnancy.
AB  - The case records of four patients with scleroderma who booked for care between
      1989 and 1994 at the Birmingham Women's Hospital (formerly the Birmingham
      Maternity Hospital), a tertiary care obstetric unit, were studied
      retrospectively. The aim of the study was to look at infertility, early and late
      pregnancy losses, fetal growth retardation and maternal complications in these
      four women afflicted with this rare condition. Two patients gave a history of
      infertility. There were two growth retarded fetuses and one intrauterine fetal
      death. Worsening Raynaud's phenomenon occurred in three patients. Another patient
      developed massive haematemesis due to an oesophageal tear resulting from
      intractable vomiting. Scleroderma may adversely affect pregnancy: obstetrical
      complications are common and require close monitoring.

PMID- 15512068
TI  - Second trimester fetal abnormality scans: do women know the reasons why they are
      done?
AB  - A 10 point questionnaire was given to 239 women attending for second trimester
      fetal abnormality ultrasound scans to explore their level of knowledge about the
      nature, purpose and limitations of the procedure. Questions were included about
      the conditions which could or could not be diagnosed, and about the accuracy and
      sensitivity of the procedure. Demographic data was also recorded. Two hundred and
      thirty-five forms were correctly completed. The percentage of women returning
      correct answers ranged from 58.8% to 100% and response rate was correlated with
      years of full time education in some questions. The results suggest that patients
      perceive the scan as a chance to see their baby and that many do not fully
      appreciate either the purpose or the limitations of fetal anomaly scanning. This
      may complicate the post-test counselling required if an abnormality is detected.

PMID- 15512069
TI  - The threat of type IV Ehlers-Danlos syndrome on maternal well-being during
      pregnancy: early delivery may make the difference.
AB  - We describe a successful management of a pregnancy in a woman with type IV Ehlers
      Danlos syndrome that included an elective caesarean section and tubal ligation at
      32 weeks' gestation. We identified 26 women (including ours) who had been
      pregnant with well-documented characteristics of type IV Ehlers-Danlos syndrome
      in the literature. These 26 women had 50 pregnancies. Ten (38.5%) died during
      pregnancy or in the immediate postpartum period. The maternal mortality rate per
      pregnancy in type IV Ehlers-Danlos syndrome was therefore calculated to be 20.0%.
      Pregnancy, continuing pregnancy, or subsequent pregnancy are all contraindicated
      in patients with type IV Ehlers-Danlos syndrome. Termination of pregnancy before
      16 weeks' gestation should be strongly advised. If the patient proceeds with
      pregnancy, restriction of physical activity at the beginning of third trimester,
      frequent evaluation of the patient, and an elective caesarean delivery at 32
      weeks' gestation after an appropriate antenatal steroid therapy should be
      advised.

PMID- 15512070
TI  - Vesico-vaginal and recto-vaginal fistulae.
AB  - In a series of 1138 patients with vesico-vaginal and/or recto-vaginal fistulae,
      the main cause in the developing world was obstructed labour, and in the
      developed world was surgery and/or malignancy. Most repairs were performed by a
      vaginal approach; there was dedicated nursing care; 85% were cured at the first
      attempt. In the developing world, prevention will require improved access to good
      obstetric care.

PMID- 15512071
TI  - The prevalence of continuing chronic pelvic pain following a negative
      laparoscopy.
AB  - This is a retrospective study to assess the prevalence of continuing symptoms in
      women following a negative laparoscopy for chronic pelvic pain. The case-notes of
      347 laparoscopies were reviewed. Of the 189 laparoscopies in which the indication
      for the procedure was chronic pelvic pain, 67 were found to be negative. This
      group of patients were each sent a questionnaire asking about continuing
      symptoms. The results of the questionnaire show that 48% of patients remain
      dissatisfied with their clinical care, 53% continue to require regular analgesics
      for their pain, 43% feel that their quality of life had been affected in a major
      way and 30% admit to feeling depressed in a major way due to their symptoms. This
      data would suggest that despite a negative laparoscopy for chronic pelvic pain, a
      significant percentage of patients would benefit from continuing medical input in
      order to help deal with their symptoms.

PMID- 15512072
TI  - Menstrual, psychosexual, psychological and somatic sequelae following postpartum
      sterilisation.
AB  - This study was designed to investigate the menstrual, psychosexual, psychological
      and somatic sequelae in a group of women who may be more prone to express regret
      following sterilisation. They were at a younger age, and all underwent postpartum
      sterilisation. The follow-up was conducted by a questionnaire between 6 months
      and 5 years following the procedure. Data were available from 242 patients with
      76.8% before age 30, and 23.2% age 30 or older. Of all the patients, 21.9%
      regretted their choice of sterilisation. About one-third had various menstrual
      cycle disturbances. In general, patients rated their sex life more enjoyable in
      many aspects. The two most common psychological symptoms were irritability,
      nervousness and depression. The common somatic symptoms were pelvic/ abdominal
      pain, backache and tiredness. A complete assessment of the patient's
      postoperative condition, including menstrual cycle history, sexual history,
      psychological and somatic complaints if any, is warranted during presterilisation
      counselling in addition to a routine informed consent. This is especially
      important for those patients who are known to be more prone to express regret
      following the procedure.

PMID- 15512073
TI  - Prolactin as a tumour marker in cancer of the cervix.
AB  - The aim of this study was to determine the possible usefulness of prolactin as a
      tumour marker in cancer of the cervix. Serum prolactin levels were measured using
      an enzyme linked immunosorbent assay in 105 women divided into malignant, pre
      malignant and control groups. Elevated levels of prolactin were found in 42.9% of
      patients with malignant disease, 22.9% of controls and 14.2% of individuals with
      premalignant disease. The differences were not statistically significant.
      Although prolactin levels were found to be elevated in some patients with
      malignant disease of the cervix, further studies are needed to establish whether
      this is of clinical significance.

PMID- 15512074
TI  - Effect of hysterectomy on ovarian blood supply and function.
AB  - Ovarian blood supply and function were assessed before and after hysterectomy in
      43 patients and 30 healthy subjects (control group). Before the hysterectomy,
      transvaginal colour Doppler resistance index values of ovarian artery and
      hormonal levels were measured. Five days and 6 months after operation, all these
      measurements were repeated and compared with those of a control group. The sole
      hormone whose serum level decreased on the 5th postoperative day was oestradiol.
      Serum levels of all the other hormones remained unchanged 5 days and 6 months
      after the surgical operations. We also did not find any statistically significant
      difference between the preoperative, the postoperative and the control group
      resistance index of the ovarian arteries. We propose that the decision whether to
      preserve or remove the ovaries must be based on assessment of their functional
      status. Advantages and disadvantages of leaving ovaries intact should be
      carefully evaluated and the most useful approach applied to each patient on an
      individual basis.

PMID- 15512075
TI  - Total versus subtotal hysterectomy: a survey of current views and practice among
      British gynaecologists.
AB  - This paper reports the results of a postal questionnaire, with a response rate of
      61 per cent. It is clear from the results that subtotal hysterectomy is an
      unpopular operation in the United Kingdom. Although a majority of consultants
      felt that subtotal hysterectomy was less likely to affect urinary, bowel and
      sexual function, this did not seem to affect decision making. Seventy-eight per
      cent of female gynaecologists would prefer a total hysterectomy for themselves
      rather than a subtotal procedure.

PMID- 15512076
TI  - The significance of Psammoma bodies in gynaecological smears and aspirates: how
      should such cases be managed?

PMID- 15512077
TI  - Prophylactic antibacterials at the time of loop diathermy excision: current
      practice in the United Kingdom.

PMID- 15512078
TI  - The diagnostic accuracy of the Pipelle endometrial sampler in the presence of
      endometrial polyps.

PMID- 15512079
TI  - Clinical and laparoscopy diagnosis of acute pelvic inflammatory disease in
      Nigeria.

PMID- 15512080
TI  - Exteriorisation, ligation and replacement of the umbilical cord in the management
      of early onset severe twin-twin transfusion syndrome.

PMID- 15512081
TI  - Annular detachment of the cervix uteri-the forgotten entity.

PMID- 15512082
TI  - Sonographic diagnosis of a unilateral tubal twin pregnancy with documented fetal
      heart activity.

PMID- 15512083
TI  - Spontaneous vaginal delivery of monoamniotic twin pregnancy despite extensive
      cord entanglement.

PMID- 15512084
TI  - Reducible inguinal swelling presenting during pregnancy-not always a hernia.

PMID- 15512085
TI  - Pregnancy with congenital adrenal hyperplasia.

PMID- 15512086
TI  - Successful perinatal outcome after 5 weeks reversed umbilical artery blood flow.

PMID- 15512087
TI  - Spontaneous vaginal vault rupture and evisceration 3 years post abdominal
      hysterectomy.

PMID- 15512088
TI  - Migrating clips: a myth or a reality?

PMID- 15512089
TI  - Displacement of the Copper-T 200 intrauterine device into the sigmoid colon.

PMID- 15512090
TI  - Occult ovarian carcinoma presenting as cerebral metastases.

PMID- 15512091
TI  - Myxoma of the ovary.

PMID- 15512093
TI  - Atypical vulval leiomyoma-a diagnostic challenge.

PMID- 15512092
TI  - Presacral dermoid cyst-an unusual presentation.

PMID- 15512094
TI  - Detached pelvic leiomyoma of uncertain origin.

PMID- 15512095
TI  - Incidental uterine amyloidosis in a 91-year-old presenting with procidentia.

PMID- 15512097
TI  - Current perspectives on drug treatment for preterm labour.

PMID- 15512098
TI  - Use of steroids, tocolytics and antibiotics in the management of preterm labour
      in Wales.
AB  - The management of preterm labour (PTL) remains contentious. Many regimes are used
      for the management of this common condition and in utero transfer of pregnant
      women to another unit is not unusual in British practice. Medical staff in the
      accepting unit may have little or no experience with one or more drug regimes
      used in this condition which used in isolation and in combination with others may
      have disastrous consequences for the mother. We have assessed the variation in
      practice for the management of preterm labour in all consultant-led obstetric
      units in Wales using a postal questionnaire. The percentage of units with written
      guidelines for the management of PTL was 40%. All units used corticosteroids
      although the regimes used varied. Fourteen of the 15 units used tocolytics.
      Ritodrine and nifedipine were the most frequently used tocolytics but there was
      much variation in practice. Only seven (46.7%) units used antibiotics and five of
      these were randomising women in PTL to the ORACLE study. Postal surveys may not
      reflect accurately what actually happens in clinical practice. These data
      demonstrate that there is no common policy for the management of PTL even in a
      relatively small region such as Wales. We would suggest that the development of a
      regional policy for the management of preterm labour would be a significant step
      forward in the management of this controversial, but important cause of neonatal
      morbidity and mortality.

PMID- 15512099
TI  - Ventouse: use, cup placement and success.
AB  - Sixty ventouse deliveries were analysed prospectively with specific attention
      paid to cup placement and its influence on successful or failed delivery. There
      was an 18.3% failure rate and 21.7% of all ventouse deliveries attempted had the
      cup inaccurately positioned. Cup placement was significantly more likely to be
      inaccurate when there was malposition of the fetal head. Significantly more
      tractions were needed when the cup was incorrectly positioned, but although there
      was a trend toward more failed attempts with the ventouse when the cup was
      inaccurately placed (23% vs 17%), this was not significant.

PMID- 15512100
TI  - Randomised trial of artemether versus artemether and mefloquine for the treatment
      of chloroquine/sufadoxine-pyrimethamine-resistant falciparum malaria during
      pregnancy.
AB  - The efficacy of artemether and artemether followed by mefloquine was evaluated in
      45 pregnant women with drug resistant Plasmodium falciparum malaria during the
      second and third trimesters. There was prompt clinical response to both treatment
      regimens. The parasite and fever clearance times and the cure rate were similar
      in both groups. Except for the correlation between initial parasite density and
      fever clearance time in the artemether-mefloquine group, there was no correlation
      between initial parasite density and parasite or fever clearance times in the two
      groups. Similarly, there was no correlation between parasite and fever clearance.
      Both treatment regimens were well tolerated. All newborn babies of the
      participating women were normal at birth. Physical and neurodevelopmental
      assessment of the newborn babies followed up for a period varying between 6 and
      36 months were within normal limits. Artemether alone or with mefloquine are
      effective and do not produce undue deleterious effects in pregnant patients with
      drug-resistant falciparum malaria during the second and third trimesters.

PMID- 15512101
TI  - Vaginal delivery following caesarean section-the use of oxytocin and
      prostaglandins.
AB  - Five hundred and twenty women with one previous caesarean section underwent a
      trial of labour in our department during the past five years. They were divided
      into three groups-those receiving oxytocin, those receiving prostaglandins, and
      those unstimulated who had spontaneous labour. The obstetric outcomes were
      compared. Rates of vaginal delivery in the three groups were 65%, 67% and 72%,
      respectively. No mother died and there were no cases of complete uterine rupture.
      Our results confirm similar reports that vaginal delivery after a previous
      caesarean section can be safely achieved in about two-thirds of patients. Serious
      complications are minimal when the use of oxytocin and prostaglandins is
      carefully monitored.

PMID- 15512102
TI  - Measurement of Cu/Zn SOD in placenta, cultured cells, various fetal tissues,
      decidua and semen by ELISA.
AB  - The concentration of copper/zinc-containing superoxide dismutase (Cu/Zn SOD) was
      measured in placental villous tissues (8-20 weeks' gestation), decidual tissues,
      cultured cells from chorionic villi and amniotic fluid cells, various fetal
      tissues (8-11 weeks' gestation), spermatozoa, seminal plasma and ovarian
      follicular fluid using a sensitive enzyme-linked immunosorbent assay (ELISA). The
      isoenzyme was expressed in all samples expect ovarian follicular fluid. Cu/Zn SOD
      was also detected in hydatidiform mole and choriocarcinoma. In placental villous
      tissues the concentration of the enzyme increased with gestation between 8 and 20
      weeks of pregnancy (n = 69, r = 0.34, P < 0.005).

PMID- 15512103
TI  - Twin pregnancy and perinatal deaths.
AB  - This is a retrospective study with the aim of revisiting twin pregnancy-a common
      obstetric problem-to determine if there are reductions in the incidence of very
      low birth weight babies, delivery problems and perinatal deaths. Three hundred
      and eight consecutive twin gestations were delivered at the hospital and an
      incidence of 21.3 per 1000 births. Preterm delivery and low birth weight babies
      accounted for 36.2% and 60.9% respectively. Breech extraction had the highest
      perinatal mortality (157.9 per 1000 births). Perinatal mortality was
      significantly high 341 per 1000 births in preterm delivery (less than 34 weeks'
      gestation). There was 50% mortality in very low birth weight category. The
      perinatal mortality of 102 per 1000 births in this study was threefold that of
      the overall hospital perinatal mortality (36 per 1000 births). Twin pregnancy,
      thus still represent a major obstetric and perinatal challenge. Provision of
      intensive multidisciplinary antenatal and intrapartum care and improvement of
      women's status would improve outcome.

PMID- 15512104
TI  - Outcome of twin deliveries at the University Teaching Hospital, Yaounde, Cameroon
      a 15-year experience.
AB  - From 1982 to 1996, a total of 16 181 deliveries was registered at the obstetric
      unit of the Yaounde University, Cameroon, out of which 291 were twins (1.8%). For
      the latter, the average gestational age was 37 +/- 2.9 weeks. In 45.0% of cases
      both fetuses presented cephalic, in 42.6% one presented cephalic and the other
      breech, while both fetuses presented as breech in 9.9% of cases. The frequency of
      the combination cephalic-transverse was 0.05%. Spontaneous delivery of both
      babies was observed in 90.2% of the patients, while in 9.7% delivery of both
      babies was by caesarian section. The caesarian section rate for a retained second
      twin was 1%. The perinatal mortality rate was 65 per 1000 (38 deaths in the first
      week of life), out of which the fetal loss was 4.4% for the first twin compared
      with 7.9% for the second. The perinatal mortality for the second twin was
      significantly associated with the type of fetal presentation at the time of
      delivery, as well as the time gap between the delivery of the twins. Sixteen
      deaths were observed amongst second twins after podalic presentation out of a
      total of 23 deaths recorded in the group. In addition, the mortality rate among
      second twins born more than 20 minutes after expulsion of the first was four
      times higher than in those delivered within 20 minutes time interval (16.0%5
      versus 4.3%). The main cause of twin deaths in our study was found to be
      prematurity which complicated 30 cases of the registered deaths (78.9%).

PMID- 15512106
TI  - An audit of the antenatal administration of steroids in women at risk of preterm
      delivery.

PMID- 15512105
TI  - What are the maternal implications of a classical caesarean section?
AB  - Sixty-two caesarean sections involving a vertical upper uterine segment incision
      were performed at the Coombe Women's Hospital between January 1983 and December
      1995. A detailed chart review was performed. There were no maternal deaths. The
      maternal outcome was complicated by infection in 49% of cases, and haemorrhage in
      19% requiring hysterectomy in two cases. In 15 subsequent pregnancies scar
      rupture occurred in one case and scar separation in two cases. The perinatal
      mortality was 200/ 1000; no perinatal death was directly related to the surgery.
      The operation is associated with a high incidence of maternal morbidity. It also
      has implications for subsequent deliveries. We recommend that every effort should
      be made to evaluate critically the need for a caesarean section in the first
      place and where possible to use a lower uterine segment transverse incision. The
      patient should be informed of the additional morbidity and long-term risks
      associated with a vertical incision.

PMID- 15512107
TI  - Emergency caesarean section in term nulliparas.

PMID- 15512108
TI  - Puerperal uterine inversion: analysis of three cases managed by repositioning,
      and literature review.

PMID- 15512109
TI  - Granulosa cell tumours of the ovary express inhibin but not CA125.

PMID- 15512110
TI  - An analysis of ectopic pregnancies following in vitro fertilisation treatment in
      a 10-year period.
AB  - Of clinical pregnancies in our in vitro fertilisation (IVF) programme, 5.4% were
      ectopic and 0.85% of clinical pregnancies (15% of ectopic pregnancies) were
      heterotopic. Ectopic pregnancies were more common after IVF/embryotransfer (ET)
      than frozen embryotransfer (FET). Although there was a suggestion that tubal
      factors were more common in those with ectopic pregnancies, the difference did
      not reach statistical significance. No relationship existed with regard to the
      ovarian stimulation regimen, the dosage/ duration of human menopausal
      gonadotrophin used, the details of embryo transfer and number of embryos
      transferred. Patients who develop ectopic pregnancies after IVF can be counselled
      that they have a good chance of achieving a normal pregnancy with subsequent
      attempts.

PMID- 15512111
TI  - Colpopexy: a modification of Shaw's technique.
AB  - The efficacy of colpopexy using an autograft is assessed. The method was used in
      patients with post-hysterectomy vaginal vault prolapse and/or suffering from
      uterine prolapse complicated by ovarian pathology. Thirty-five patients were
      subjected to a modified operative procedure based on Shaw's original method and
      completed with a posterior colporrhaphy. All patients are now free of urinary
      and/or pelvic symptoms with a functional vagina, after a 48 to 60 months post
      operative follow-up. Pelvic cellulitis was observed in two patients and low
      abdominal pain in three others for a period of 1 month.

PMID- 15512112
TI  - Urinary tract fistulas following gynaecological surgery.
AB  - Urinary tract fistulas are a relatively uncommon but important complication of
      gynaecological surgery. Between 1980 and 1995 we identified 17 patients who
      developed a urinary tract fistula after gynaecological surgery. Seven of the
      patients had surgery performed for neoplastic disease but none of these patients
      received adjuvant radiotherapy before the formation of the fistula. There were 12
      vesicovaginal fistulas and five ureteric fistulas. Four of the vesicovaginal
      fistulas were repaired by the vaginal approach and five vesicovaginal fistulas
      were repaired by the abdominal route. Three vesicovaginal fistulas were treated
      by catheterisation alone. Two of the 17 patients took medicolegal action. Early
      recognition and repair of urinary tract fistulas is recommended. Repair of
      vesicovaginal fistulas by the vaginal approach is advised. The litigious nature
      of this distressing condition is lessened when early primary closure is
      successful.

PMID- 15512113
TI  - Local anaesthesia for large loop excision of the cervical transformation zone:
      has prilocaine/felypressin less side effects than lignocaine/adrenaline?

PMID- 15512114
TI  - Hysterectomy for moderately enlarged uterus: abdominal versus vaginal
      hysterectomy.

PMID- 15512115
TI  - Plasmapheresis in the management of HELLP syndrome.

PMID- 15512116
TI  - Severe secondary postpartum haemorrhage successfully managed by vaginal
      myomectomy.

PMID- 15512117
TI  - Extra-cranial frontal teratoma-case report and recommendation for treatment.

PMID- 15512118
TI  - Spontaneous uterine rupture at 15 weeks of gestation due to placenta percreta.

PMID- 15512119
TI  - Delivery through an undiagnosed major placenta praevia: good outcome for mother
      and baby.

PMID- 15512120
TI  - Acute fetal anaemia: a case of feto-maternal transfusion.

PMID- 15512121
TI  - Cervico-vaginal cyst following knife cone biopsy of the cervix.

PMID- 15512122
TI  - Unusual presentation of ovarian tumour of borderline malignancy.

PMID- 15512123
TI  - Successful management of intractable menorrhagia with a levonorgestrel-releasing
      intrauterine device, in a woman with a bicornuate uterus.

PMID- 15512124
TI  - Rupture of a rudimentary uterine horn at 19 weeks' gestation.

PMID- 15512125
TI  - Puerperal primary pneumococcal peritonitis.

PMID- 15512126
TI  - Deep vein thrombosis secondary to compression by uterine leiomyoma.

PMID- 15512127
TI  - Limitations associated with the use of the pipelle sampler.

PMID- 15512130
TI  - The pathophysiology, prevention and management of the ovarian hyperstimulation
      syndrome.

PMID- 15512131
TI  - The impact of nitric oxide on gynaecology.

PMID- 15512132
TI  - Cerebral magnetic resonance imaging in eclampsia: a series of 12 cases.
AB  - The object of this study was to assess the ability of magnetic resonance imaging
      (MRI) to detect the cerebral abnormalities associated with eclampsia and
      therefore to establish its place in our management of the condition. This study
      was of particular relevance to our institution because eclampsia is common in our
      patient population. This was a prospective study in which 13 patients with an
      initial diagnosis of eclampsia received MRI brain scans. Of 12 patients with a
      final diagnosis of eclampsia, seven (58.3%) showed the typical MRI changes of
      eclampsia, namely cerebral hyperintensities representing focal areas of oedema.
      In five patients (41.6%) the scans were normal. The rate of abnormality detection
      was surprisingly low. We conclude that the reason for this was the time delay in
      obtaining the scans. The cerebral changes in eclampsia can be rapidly reversible.
      Future studies must aim to perform MRI within 48 hours of seizure activity. MRI
      is more sensitive than computed tomography scanning but has no practical
      advantages over computed tomography except where the diagnosis is in doubt.

PMID- 15512133
TI  - Ruptured uterus in Kaduna, Nigeria: a six-year review.
AB  - A six year review in a Nigerian University Teaching Hospital revealed that the
      incidence of ruptured uterus is 1 per 137 deliveries. The mean age of patients
      was 30.5 years. Ruptured uterus occurred in younger women with a scarred uterus
      compared with the unscarred group. The incidence of ruptured uterus was highest
      in women who were para 5 and above. Cephalopelvic disproportion was the most
      important obstetric factor associated with rupture (63.4%). Abdominal tenderness
      (46.3%), vaginal bleeding (31.7%) and pallor (31.7%) were the commonest clinical
      features at presentation. Shock (22%) was commonest in the unscarred group.
      Repair with tubal sterilisation was the commonest method of treatment. Diarrhoea
      was the commonest postoperative complication (39%). Maternal and perinatal
      mortality rates were 22% and 88% respectively. Improving the emergency capability
      of the hospital and more efforts at educating our women and reducing poverty will
      go a long way towards reducing the incidence and adverse clinical outcome of
      ruptured uterus.

PMID- 15512134
TI  - Outcome of ruptured uterus at University Teaching Hospital Aleppo, Syria.
AB  - A 10-year review of ruptured gravid uterus at the University Teaching Hospital,
      Aleppo, Syria showed an incidence of one ruptured uterus in 565 deliveries. This
      is an average figure compared with published studies but is still high compared
      with developed countries. Sixty-four per cent of the cases of ruptured uterus had
      no antenatal care. It is no surprise therefore that maternal and fetal mortality
      was highest amongst the unbooked labouring women. In survivors the morbidity was
      also higher. Ruptured uterus is therefore a major cause of maternal and perinatal
      mortality and morbidity in Syria. The overall hospital maternal and perinatal
      mortalities for the period under review were 4.3% and 2.6% respectively. The main
      risk factor identified is scarring from previous caesarean sections. Other risk
      factors are discussed.

PMID- 15512135
TI  - Rupture of the uterus in labour: a review of 14 cases in a general hospital.
AB  - This study aimed to identify the risk factors and clinical presentations
      associated with rupture of the uterus in labour and to determine material and
      fetal outcomes. Rupture of the uterus is a potentially devastating complication
      of childbirth and remains one of the major causes of maternal and perinatal
      mortality and morbidity.

PMID- 15512136
TI  - Commentary: Ruptured uterus.

PMID- 15512137
TI  - Primary and repeat caesarean sections: comparison of indications.
AB  - In this retrospective study, we describe and compare the clinical indications of
      primary and repeat caesarean sections. We review caesarean deliveries at the
      Princess Badeea Teaching Hospital in North Jordan performed between 1 January and
      26 November 1995 (n=740). The indication for the procedure was extracted based on
      the surgeon's operative reports. The hospital caesarean rate during the study
      period was 8.8%; 22.7% of these were repeat procedures (n=168). Elective
      caesarean delivery was the leading cause of repeat sections, followed by
      dystocia, others, breech and fetal distress. In contrast, breech presentation,
      dystocia and fetal distress were the leading indications for primary caesarean
      section. Ninetynine patients (59%) undergoing repeat caesarean had absolute or
      relative contraindication to trial of labour. The majority of primary caesarean
      are clinically indicated. Caesarean section rates can be lowered if we address
      the repeat elective procedures.

PMID- 15512138
TI  - 'Expert' analysis of menstrual and ultrasound data in pregnancy--gestational
      dating.
AB  - The expected date of delivery (EDD) using a precise ultrasound day rule was
      compared with the scan EDD alone in 219 singleton pregnant women who were certain
      of their last menstrual period, and booked in the obstetric department of a
      district general hospital. The system compared the ultrasound biometric
      measurement with the normal range of a published chart of fetal size and, using
      the day rule concept, the final EDD selected by an 'expert' computer system.
      Statistical analysis using similar methods as in other published studies showed
      that the 'expert' system correlated with the actual date of the onset of
      spontaneous labour at least as well as scan dates alone. Menstrual data should
      not be rejected in favour of ultrasonic biometry in all cases and a computer
      system using a precise day rule should be a valuable addition to computerised
      maternity databases and ultrasound machines.

PMID- 15512139
TI  - Experience with selective external cephalic version at term in Saudi Arabia: a
      three year review.
AB  - Thirty-six patients were selected for external cephalic version at term in an
      attempt to reduce the number of caesarean sections performed for breech
      presentation. All had the option of elective caesarean section on account of a
      big fetus or small maternal pelvis. Our results showed that 20 fetuses out of 24
      (83.3%) who had a successful external cephalic version went on to vaginal
      delivery.

PMID- 15512140
TI  - What is the normal heart rate of a term fetus?
AB  - There is controversy about the value of continuous versus intermittent
      auscultation of the fetal heart during labour, but there is no agreement on what
      constitutes normal heart rate of a term fetus. There are variations between the
      definitions adopted by different countries, and even within a single country. We
      propose 110-160 beats per minute for clinical use.

PMID- 15512141
TI  - Comparison of the intrapartum analysis of Doppler blood flow velocity waveform of
      the umbilical artery and fetal heart rate tracing for the prediction of perinatal
      outcome.
AB  - This study was performed to determine the value of umbilical artery Doppler flow
      velocity waveform (FVW) analysis and fetal heart rate (FHR) tracing in the course
      of labour for predicting poor perinatal outcome. The randomised, controlled and
      prospective study was carried out on 99 singleton term pregnant women in labour
      at the Zeynep Kamil Women and Children's Hospital, Istanbul. All patients were
      evaluated by both methods during the intrapartum period. Blood gases and pH of
      umbilical venous blood and 1 and 5 minute Apgar scores of the newborn infants
      were determined immediately after delivery. For the prediction of poor perinatal
      outcome, the sensitivity, specificity, negative predictive value and positive
      predictive value of FHR were 72.0%, 85.1%, 60.1% and 90.0%, respectively. FHR was
      pathological in all four cases with a neonatal death, whereas only two had
      pathological Doppler FVW. We conclude that FHR is a more sensitive method than
      umbilical artery Doppler FVW analysis (72.0% versus 36.0%) in the prediction of
      poor perinatal outcome during the intrapartum period. A combination of the two
      tests increases the specificity of the prediction of poor perinatal outcome from
      89.2% and 85.1% to 94.9%. High negative predictive values of both tests should
      reassure the clinician when the test results are normal.

PMID- 15512142
TI  - Low values on 50 gram glucose challenge test or oral 100 gram glucose tolerance
      test are associated with good perinatal outcome.
AB  - We set out to reevaluate the hypothesis that high normal (negative) results of 50
      g oral glucose challenge test or high normal glucose level on 100 g oral glucose
      tolerance test are associated with complications of pregnancy and delivery. This
      was a prospective study involving 735 nondiabetic women. The first group (n=352)
      was made up of pregnant women with normal 50 g oral glucose challenge test
      without previous history of diabetes mellitus or gestational diabetes. The second
      group (n=383) was made up of pregnant women without previous history of diabetes
      mellitus or gestational diabetes with an abnormal 50 g oral glucose challenge
      test and with normal 100 g oral glucose tolerance test and not more than one
      previous delivery. In nondiabetic women, we demonstrated a positive correlation
      between high normal 50 g glucose challenge test values and the incidence of
      preeclampsia, caesarean section rate, macrosomia, neonatal hyperlipidaemia and
      minor congenital abnormalities. We failed to confirm any relationship to any
      pregnancy complication in pregnant women with 2-hour glucose levels in the range
      6.7-9.1 mmol/l on the 100 g oral glucose tolerance test. We have demonstrated a
      positive relationship between the incidence of premature rupture of membranes and
      1-hour glucose level, caesarean section rate and maternal 1-hour glucose level or
      1-hour glucose level minus fasting glucose level of 4.2 mmol/l, instrumental
      delivery rate and maternal 3-hour glucose level, incidence of neonatal macrosomia
      and 1-hour glucose level, and incidence of neonatal hyperlipidaemia and at least
      one high but normal glucose level on the 100 g oral glucose tolerance test. With
      regard to pregnancy and delivery complications there were no significant
      difference if the high normal value is on the 50 g glucose challenge test or on
      the 100 g oral glucose tolerance test. It is concluded that one high normal 100 g
      oral glucose tolerance test or high normal 50 g glucose challenge test are
      associated with adverse pregnancy and delivery outcome. Nondiabetic women with 50
      g glucose challenge test value of 6.1 mmol/l and/or 100 g oral glucose tolerance
      test values of 5 mmol/l have a favourable pregnancy and delivery outcome.

PMID- 15512143
TI  - Maternal plasma glycaemia and fetal outcome in north-eastern Nigeria.
AB  - This paper aims to assess the influence of maternal glycaemia and other clinical
      indices on the birthweight of babies born to Nigerian women resident in
      Maiduguri. Eighty-four pregnant women (aged, 25.7 0.5 years, mean SE) in the
      third trimester of pregnancy were recruited for the studies. Blood pressure,
      weight and height were measured while other social variables were obtained by
      questionnaire. Fasting and 2-hour blood samples, after 75 g oral glucose load,
      were collected for plasma glucose measurements. None of the women was a known
      diabetic while 3.6% were known hypertensives. The mean SE fasting (4.2 0.11
      mmol/l) and 2-hour (5.8 0.19 mmol/l) plasma glucose concentrations and the
      systolic (111 1.20 mmHg) and diastolic (72 0.96 mmHg) blood pressures were normal
      by WHO criteria. Incidence of macrosomic babies was nil. The birthweight of the
      babies was not significantly related to either the fasting plasma glucose (r=
      0.11, P 0.05) or 2-hour postprandial glucose concentrations (r=-0.09, P 0.05),
      but was significantly related to the maternal pre-pregnancy bodyweight (r=0.30, P
      0.05) and body mass index (BMI) (r=0.31, P 0.05). It is concluded that Nigerian
      women resident in Maiduguri maintain a normal glucose tolerance during the third
      trimester of pregnancy. Pre-pregnancy body weight and BMI, and not plasma
      glycaemia, would seem more important factors associated with the birthweight of
      babies born in this Nigerian population.

PMID- 15512144
TI  - A comparison of an intravaginal controlled release prostaglandin E2 (10 mg) for
      cervical ripening and initiation of labour versus prostaglandin E2 vaginal tablet
      (3 mg).

PMID- 15512145
TI  - Women's experiences of having a colposcopic examination: self-reported
      satisfaction with care, perceived needs and consequences.
AB  - This study was conducted in seven gynaecological clinics in New South Wales
      (NSW), Australia. The study aimed to assess the level of satisfaction with care,
      unmet needs and consequences following the procedure reported by women having a
      colposcopic examination. Of the 161 eligible women attending colposcopy clinics
      who were approached to take part, 156 (97%) gave written consent to participate
      and 138 (86%) completed interviews. Consenting women were telephoned within 1
      week of their clinic visit to complete a computer-assisted telephone interview
      (CATI). The survey addressed a number of issues relating to the care they
      received during their colposcopic examination: satisfaction with care,
      satisfaction with the waiting time to have a colposcopy, preferences for provider
      gender, information and health care needs while waiting for the colposcopy,
      information and health care needs during the colposcopy, short-term physical
      consequences and shortterm psychosocial consequences of the procedure. Results
      indicate that satisfaction with care among women ranged from 69% to 96%. The
      highest expressed needs while waiting for the colposcopy were for information
      about risks of cancer (91%), reasons for needing a colposcopy (86%), and the
      colposcopy procedure (86%). Women reported that outcomes such as anxiety and
      disinterest in sex had further worsened or not been improved following the
      colposcopy. The results indicate that interventions to address specific concerns
      would need to be designed, implemented and evaluated.

PMID- 15512146
TI  - Patient satisfaction with daycase laparoscopy.
AB  - A prospective audit was performed on all patients preselected for daycase surgery
      over a 3-month period. The aim of the study was to evaluate patient acceptability
      and satisfaction with laparoscopy performed as a daycase procedure. Patients
      completed standard questionnaires before operation and at 4 weeks after surgery.
      Questions included satisfaction with daycase surgery, subjective pain experience,
      time taken to resume normal activities, adequacy of analgesia and necessity to
      call general practioners. Analysis of results revealed that 69% of patients were
      satisfied with day surgery laparoscopy. However there were highly significant
      differences (P less than 0.001) between resumption of normal activity, pain
      experienced and length of stay between patients satisfied and dissatisfied with
      daycase surgery. This study suggests that guidelines for daycase procedures may
      be overambitious as 31% of patients already pre-selected, were dissatisfied with
      daycase surgery.

PMID- 15512147
TI  - An evaluation of transvaginal ultrasound-guided aspiration of simple adnexal
      cysts.
AB  - We carried out this clinical study to evaluate the benefits the risks of
      transvaginal ultrasound-guided aspiration in a group of patients. The study group
      consisted of 22 premenapausal women who were detected as having benign adnexal
      cysts, based on ultrasound appearances. Before the procedure, all patients were
      evaluated thoroughly by pelvic examination, transvaginal ultrasound and serum
      measurements of CA-125. Oestradiol CA-125, follicle stimulating hormone,
      luteinising hormone and progesterone were analysed in aspirated cystic fluids as
      well as cytological evaluation. It was concluded that measurements of follicle
      stimulating hormone, luteinising hormone, oestradiol and progesterone
      concentrations in cystic fluid had no prognostic significance. But CA-125 levels
      over 55 iu/ml were likely to predict the recurrence of the cysts. Cytological
      examination of the aspirated cystic fluids revealed that 21 cysts were benign
      functional cysts, but one was serous cystadenoma. We observed recurrence
      following aspiration in five patients (22.7%) who were followed for 6 months.
      Patients with simple ovarian cysts will benefit from transvaginal ultrasound
      guided aspiration by being saved from surgery and its related complications.
      However, its use should be limited to those masses that appear to be completely
      cystic with well-defined borders, because of the risk of the intra-abdominal
      spillage of the contents of complicated cysts.

PMID- 15512148
TI  - Do blunt tipped needles reduce the risk of glove puncture and needlestick injury
      in the suture of episiotomy and perineal repair?

PMID- 15512149
TI  - Successful second pregnancy following transcervical endometrial resection.

PMID- 15512150
TI  - Not all that fits in pregnancy is eclampsia: a lesson.

PMID- 15512151
TI  - Sonographic diagnosis of subacute puerperal uterine inversion.

PMID- 15512152
TI  - Polyhydramnios: an association with congenital myotonic dystrophy.

PMID- 15512153
TI  - Hodgkin's disease in pregnancy.

PMID- 15512154
TI  - Vesico-cutaneous fistula with a valvular stone--an unusual complication following
      gauze-hammock sling operation.

PMID- 15512155
TI  - A case of spontaneous umbilical endometriosis.

PMID- 15512156
TI  - Intravenous leiomyomatosis of the uterus: a GnRH agonist utilisation before
      surgery.

PMID- 15512157
TI  - Prolapsed ovarian cyst through cervical stump: a rare complication of a subtotal
      hysterectomy.

PMID- 15512158
TI  - Possible persistent trophoblastic activity after partial salpingectomy for
      ectopic pregnancy.

PMID- 15512159
TI  - Laparoscopic management of a rudimentary uterine horn pregnancy.

PMID- 15512161
TI  - Dyskaryotic glandular cells on a cervical smear warrant a thorough investigation
      for a site.

PMID- 15512160
TI  - Wandering calcified teratoma.

PMID- 15512162
TI  - Minimal compliance with the Department of Health (DoH) guidelines for folic acid
      prophylaxis to prevent neural tube defects.

PMID- 15512165
TI  - Thyroid disorders and pregnancy.
AB  - During pregnancy physiologic changes in thyroid function occur which should not
      be misinterpreted as pathological. Thyroid disorders may complicate pregnancy and
      need thorough investigation and treatment in order to ensure a favourable
      pregnancy outcome. The incidence of hyperthyroidism in pregnant women has been
      reported to be approximately 0.2%. The leading cause is Graves' disease.
      Treatment of hyperthyroidism includes antithyroid drugs or surgery to avoid
      adverse effects on the neonate such as prematurity, intrauterine growth
      retardation and fetal or neonatal thyrotoxicosis. Use of radioactive iodine is
      contraindicated. Hypothyroidism during pregnancy is associated with gestational
      hypertension and low birth weight. Women on thyroid replacement therapy before
      pregnancy may require an increase in dosage during pregnancy. Pregnant women with
      chronic autoimmune thyroiditis have a higher incidence of spontaneous
      miscarriage. Nodular disease demands meticulous investigation to rule out a toxic
      adenoma or malignancy. Surgery in the case of cancer can be postponed under
      certain circumstances. Within one year following delivery, about 5-10% of women
      may exhibit postpartum autoimmune thyroid dysfunction, which may result in
      hypothyroidism.

PMID- 15512166
TI  - Vaginal melanoma: a current review.
AB  - Vaginal melanoma is rare, accounting for less than 3% of primary vaginal tumours.
      It principally affects postmenopausal women, however no risk factors have been
      identified. Patients frequently present with vaginal bleeding, but the tumour is
      locally advanced at presentation. Surgery is only the potential cure. The
      relative merits of radical surgery-vaginectomy and iliac or inguinal
      lymphadenectomy-versus wide local excision with prompt treatment of recurrences
      remains uncertain. High dose external radiotherapy and regional chemotherapy
      trials have been encouraging, although there is no definite survival advantage.
      Patients should be offered excisional therapy with the opportunity to participate
      in trials of adjuvant therapy. Prognosis is poor with a five-year survival of 5
      21%. Effective screening measures are required enabling earlier diagnosis.

PMID- 15512167
TI  - Does the attending obstetrician influence the mode of delivery in the 'standard'
      nullipara?
AB  - We have investigated whether the attending obstetrician has an influence on the
      mode of operative delivery by examining practices of obstetricians working at a
      district general hospital in the United Kingdom over 3 years. Nulliparous women (
      n = 1410) with a singleton, cephalic and term fetus who had an operative delivery
      were studied. The most senior obstetrician present at 89% of these deliveries was
      one of the 12 registrars training in the unit. The proportion of women delivered
      by each mode of vaginal or abdominal operative delivery by each registrar was
      compared. In nine of these registrars the proportion of women they delivered by
      at least one mode differed significantly from the others. Caesarean section after
      an unsuccessful attempt at operative vaginal delivery showed the largest
      variation and caesarean section before the second stage of labour showed the
      least, with vaginal operative delivery modes and caesarean section in the second
      stage without a trial of vaginal delivery intermediate between the two. The
      method can be used to provide a 'profile' of the preferences exercised by
      individual operators.

PMID- 15512168
TI  - Efficacy of chloroquine plus chlorpheniramine in chloroquine-resistant falciparum
      malaria during pregnancy in Nigerian women: a preliminary study.
AB  - The efficacy of chloroquine plus chlorpheniramine, a histamine H receptor
      antagonist, which reverses chloroquine 1 insensitivity in Plasmodium falciparum
      in vitro and in vivo , was evaluated in 30 pregnant women with recrudescent
      chloroquine-resistant Plasmodium falciparum malaria. All patients had at least
      one or more treatment failures with one or more courses of chloroquine or
      pyrimethamine-sulphadoxine. There was a prompt response to treatment with
      parasitaemia and fever clearing in all patients within 48 and 96 hours
      respectively of commencement of therapy with the combination. The cure rate on
      day 14 was 77%. Parasitaemia recurred in seven patients after day 14 and was
      successfully treated with oral mefloquine. The combination was well tolerated;
      pruritus and drowsiness were the only noticeable adverse effects. The progress of
      pregnancy and its outcome were not adversely affected by treatment with the
      combination. When fully developed, the combination of chloroquine plus
      chlorpheniramine may be an alternative in the treatment of chloroquine-resistant
      malaria during pregnancy in Nigerian women.

PMID- 15512169
TI  - Knowledge, attitude, and practices related to hepatitis B virus infection among
      Nigerian obstetricians and midwives.
AB  - Obstetricians and midwives are exposed to the blood, vaginal secretions and
      amniotic fluid of their patients during vaginal examinations, deliveries,
      intracavity procedures and resuscitation of the newborn. They are therefore at
      risk of hepatitis B virus (HBV) infection that is endemic in developing
      countries. We studied the knowledge, attitude, and practices of obstetricians and
      midwives in four teaching hospitals in Southwestern Nigeria with respect to HBV
      infection. A self-administered questionnaire was used to elicit information about
      their demographic characteristics, knowledge about, and immunisation against HBV
      and the use of barrier methods. There were 83 respondents with a mean age of 34.9
      years, 45 were midwives while 38 were obstetricians. The former had practised for
      a range of 2-26 years while the latter had practised for 1-16 years. In a test of
      knowledge about HBV infection, obstetricians had a mean score of 2.4 while
      midwives scored 1.8 marks out of five. Only 18.1% had received HBV immunisation
      and 8.4% always screen their patients for HBV antigens; 33.7% always use barrier
      methods with the commonest reason for non-use being non-availability. The
      difference in knowledge between obstetricians and midwives was statistically
      significant. In conclusion, we make recommendations about reducing the risk of
      occupationally acquired HBV infection in the labour ward.

PMID- 15512170
TI  - Emergency peripartum hysterectomy.
AB  - A total of 54 166 mothers delivered at the Riyadh Armed Forces Hospital between
      1990 and 1997, including 6119 (11.3%) caesarean sections. Emergency peripartum
      hysterectomy for obstetric haemorrhage was carried out in 16 cases (0.3/1000
      deliveries). The operation followed major degrees of placenta praevia in 12 (75%)
      cases and atonic postpartum haemorrhage in four (25%). All patients required
      blood transfusion. There was one neonatal death and no maternal deaths. Although
      the operation was straightforward, bladder injury occurred in five (31%) cases
      which was repaired with no residual damage. Placenta accreta was confirmed
      histologically in 12 (75%) patients. In conclusion, all obstetricians should be
      aware of the strong association between a scarred uterus, placenta praevia and
      placenta accreta which can be very adherent and difficult to remove causing
      bleeding and necessitating hysterectomy. The operation should be performed by an
      experienced obstetrician before the patient's condition is extreme.

PMID- 15512171
TI  - Labour ward activity and the lunar cycle.
AB  - To refute the commonly held belief by the general public that the lunar cycle
      affects labour, we studied 10 027 deliveries over an 18-month period in a large
      maternity unit in Ireland. There was no increase in the total number of
      deliveries during the times of a full moon compared with other times. The
      caesarean section, instrumental vaginal delivery, and pre-term delivery rate
      remained unchanged over the times of a full moon. We conclude that the lunar
      cycle has no influence on labour ward activity.

PMID- 15512172
TI  - Neonatal morbidity associated with disproportionate intrauterine growth
      retardation at term.
AB  - We set out to compare neonatal morbidity between disproportionate intrauterine
      growth retarded newborn infants and proportionate retarded ones at term, based on
      ponderal index. This is a prospective study of 185 single pregnancies with
      evidence of intrauterine growth retardation at term. Sixty three cases (34%) were
      disproportionate and 122 (66%) proportionate in terms of ponderal index. All were
      born in the University Hospital 'Principe de Asturias' of Alcala de Henares,
      Madrid, Spain. Proportionate or disproportionate intrauterine growth retardation
      diagnosis was established using the ponderal index (weight/length3). The
      following outcomes of neonatal morbidity were investigated: (1) perinatal
      asphyxia (meconium-stained amniotic fluid, abnormal fetal heart rates, newborn
      acidosis or low Apgar score 7 at 5 minutes) and/or (2) early neonatal medical
      complications. Disproportionate intrauterine growth retardated newborn infants
      presented higher rates of perinatal asphyxia (54% vs. 32%, P 0.01), with higher
      abnormal fetal heart rates (37% vs. 15%, P 0.01), higher frequency of arterial pH
      7.20 (31% vs. 16%, P 0.05); and also higher rates of early neonatal medical
      complications (40% vs. 11%, P 0.001), mainly hypoglycaemia (25% vs. 4%, P 0.01).
      Morbidity among disproportionate intrauterine growth retardated Aconates is
      significantly higher compared with proportionate ones, demonstrating the
      heterogeneity of the intrauterine growth retardation population. Proportionate
      and disproportionate intrauterine growth retardation should be diagnosed as early
      as possible, since the majority of the morbidity is intimately related to this
      difference.

PMID- 15512173
TI  - Surgical management of herniated lumbar disc in pregnancy.

PMID- 15512175
TI  - Evidence of growth restriction in unexplained stillbirths.

PMID- 15512174
TI  - Comparison of four different antibiotics as prophylaxis in caesarean section.

PMID- 15512176
TI  - Pre-eclampsia and chromosomal anomalies.

PMID- 15512177
TI  - A double-blind randomised study comparing danazol and medroxyprogesterone acetate
      in the management of menorrhagia.
AB  - A randomised study was undertaken comparing danazol 200 mg daily and
      medroxyprogesterone acetate 10 mg daily from days 16 to 25 in the management of
      menorrhagia. Twenty-three women were recruited to the study over a 12-month
      period. Eighteen subjects were suitable for analysis. Three months' therapy was
      given and patients were observed for a 3-month period following discontinuation
      of therapy. Menstrual blood loss was estimated during initial patient assessment
      and then during each of the 6 months of the study. In the danazol group mean
      blood loss at all treatment phase months was significantly decreased from
      baseline. In contrast, blood loss was not reduced significantly in any study
      month when compared with baseline in the medroxyprogesterone acetate group.
      During the post-treatment phase the mean blood loss in the danazol group
      increased to above normal levels but remained significantly lower than baseline,
      and there was a significant reduction in menstrual blood loss in the
      medroxyprogesterone acetate group.

PMID- 15512178
TI  - Gynaecological and microbiological findings in women attending for a general
      health check-up.
AB  - Two hundred apparently healthy sexually active women, 17-34 years of age, who had
      presented for a general health check-up at the Clinic of Dermatology and
      Venereology, Medical University, Plovdiv, Bulgaria, were asked about genital
      symptoms, sexual behaviour, contraceptive use and smoking habits, and examined
      for signs of genital infections. They were searched for genital chlamydial
      infection, gonorrhoea, trichomoniasis, bacterial vaginosis (BV) and vulvovaginal
      candidosis, syphilis and HIV. Polymerase chain reaction (PCR) was used for
      detection of Chlamydia trachomatis and Neisseria gonorrhoeae in urine samples and
      the results were compared with direct immunofluorescence (DFA) and enzyme
      immunoassays (EIA) for C. trachomatis in urethral, cervical and urine samples. In
      56 (28%) women, an STD and/or an STD-related condition were diagnosed. The
      prevalence of genital chlamydial infection, trichomoniasis, BV and vulvovaginal
      candidosis was 4.5%, 0.5%, 17.5% and 7.5% respectively. On direct questioning 39
      (19.5%) women reported symptoms suggestive of an infection, while 58 (29%) had
      signs that may have been caused by genital infection. In urine the PCR tests
      detected more (3.5%) chlamydia-positive women than the DFA (2.5%) and EIA tests
      (1.5%). The urine PCR test was as sensitive as the DFA when testing cervical
      samples. The chlamydia-positive women and women with BV were less likely to have
      a steady partner than the controls. No woman had syphilis or HIV infection. The
      women with BV were more frequent users of an intrauterine device and were more
      likely to smoke heavily compared with other women. STDs and STD-related
      conditions are common among adult women who consider themselves gynaecologically
      healthy. Screening for genital infections among women in reproductive age
      attending for health check-up could improve women's reproductive health.

PMID- 15512179
TI  - 'Don't be fooled by the patient's make-up'!
AB  - One hundred and eighty-seven patients undergoing gynaecological surgery in two
      different international centres were reviewed daily by 'blinded' interviewers.
      They were analysed for the presence of nausea, vomiting, eating, mobilisation,
      general well-being and use of make-up. On starting to wear make-up their
      statement of well-being improved significantly but 1 in 3 patients in London
      complained of nausea, one in four still had a urinary catheter in place, required
      intramuscular analgesia or intravenous access, one in eight were unable to
      tolerate food, and one in 10 patients were pyrexial. Although wearing make-up was
      associated with improved well-being their was no correlation with their clinical
      condition.

PMID- 15512180
TI  - Adenomyosis following endometrial resection--a retrospective study.
AB  - The aim of this study was to evaluate the presence of adenomyosis in women
      following endometrial resection who subsequently undergo hysterectomy. Out of 227
      women who underwent endometrial resection 9.3% (21) subsequently had a
      hysterectomy. Of these, 28.5% were shown to have adenomyosis on histological
      examination compared with a case control group incidence of 7.5%.

PMID- 15512181
TI  - A new approach in the management of lower Mullerian atresia.
AB  - Over the past 20 years we have encountered 13 cases of lower genital tract
      atresia or obstruction. There were eight cases due to a high transverse vaginal
      septum. These were dealt with by standard surgical reconstruction. One later
      recurred and required hysterectomy. Five patients presented with cervical
      atresia. These were successfully treated by a new abdomino/vaginal approach. All
      menstruated normally after the procedure and one became pregnant and delivered a
      normal baby by caesarean section at term. None of the cases had recurrent
      obstruction and none required hysterectomy.

PMID- 15512182
TI  - Features of uterine fibroids treated by abdominal myomectomy at Nnewi, Nigeria.
AB  - Seventy-two women with symptomatic uterine fibroids were treated by abdominal
      myomectomy from January 1994 to December 1996. Important features were a mean age
      of 32.3 years (range 25-49 years) and parity of 0 to 6; 83% ( n = 60) were
      nulliparous and 68% ( n = 49) were unmarried. The average estimated blood loss
      was 480 ml with 1.6 g/dl mean haemoglobin drop and 15.3% required blood
      transfusion. Complications were mild and infrequent; 7% ( n = 5) had mild wound
      infection and 16.7% ( n 12) had a febrile complication. The average hospital stay
      was 8.1 days. There was no mortality. In this study, symptomatic uterine fibroids
      requiring abdominal myomectomy predominantly affected young women who were mainly
      unmarried and nulliparous. Although the the operation was safe and well
      tolerated, preoperative GnRH(a) is recommended to reduce fibroid size and need
      for blood transfusion.

PMID- 15512183
TI  - Bacterial vaginosis and cervical intraepithelial neoplasia--cause or coincidence?
AB  - Evidence regarding a causal relationship between bacterial vaginosis and cervical
      intraepithelial neoplasia has so far been incomplete and conflicting. To
      determine whether bacterial vaginosis is associated with cervical intraepithelial
      neoplasia a retrospective study was conducted at the Genitourinary Medicine
      Clinic at Southlands Hospital, Shoreham-by-Sea, UK. Three hundred patients who
      presented to the clinic with a first diagnosis of genital warts in the absence of
      other sexually transmitted diseases were recruited. Results of cervical cytology
      and where abnormal, histology on colposcopically directed punch biopsies were
      collected. Bacterial vaginosis was diagnosed by the detection of clue cells on
      Gram-staining of a high vaginal swab, positive amine test, vaginal pH above 4.5
      and the presence of characteristic vaginal discharge. Odds ratio showed an
      increased prevalence of cervical intraepithelial neoplasia associated with
      bacterial vaginosis. The results suggest that a prospective cross sectional study
      should be performed to formally test the hypothesis that bacterial vaginosis
      predisposes to cervical intraepithelial neoplasia.

PMID- 15512184
TI  - Bioavailability of oestradiol from the Alora (0.1 mg/day) oestradiol matrix
      transdermal delivery system compared with Estraderm (0.1 mg/day).
AB  - This open-label, randomised, two-way crossover study compared the steady-state
      bioavailability of oestradiol administered by way of a new oestradiol matrix
      transdermal delivery system (Alora 0.1 mg/day) with that of Estraderm (0.1
      mg/day) in 24 subjects. Serum oestradiol, oestrone and oestrone sulphate
      concentrations were determined by measurement of blood samples. Mean SD pre
      dosing, nonadjusted oestradiol levels for Alora (71.9 27.0 pg/ml) were
      substantially higher than those for Estraderm (26.7 9.7 pg/ml), while peak
      oestradiol concentrations were comparable. Consequently, fluctuations in steady
      state levels were substantially smaller for Alora than for Estraderm; the
      fluctuation index values (?[C- C ])/ max min C ) were significantly lower for
      Alora (0.97 0.23) than av for Estraderm (1.68 0.45). Oestradiol levels remained
      constant over the dosing interval with Alora but decreased significantly after 48
      hours with Estraderm. The bioavailability of oestradiol with Alora was 127 56%
      that of Estraderm. Oestrone and oestrone sulphate data showed the same
      qualitative and quantitative differences between the two systems. Both systems
      were well tolerated. In summary, Alora delivered more oestradiol to the systemic
      circulation with greater consistency and over a longer time than did Estraderm.

PMID- 15512185
TI  - Headless spermatozoa in fertile men.
AB  - Headless or unucleated spermatozoa were evaluated in semen specimens of 52
      fertile men in order to investigate the frequency and the percentage of this
      morphological abnormality and to estimate the probable correlation of the
      abnormality with other semen parameters, since there are no available data. The
      only sperm parameter which correlated with the number of headless spermatozoa was
      the number of micro round-headed spermatozoa (r= + 0.4432, P<0.001). It is
      concluded that the high frequency of headless or unucleated spermatozoa in the
      semen specimens of fertile men, albeit in low percentage, does not seem to have
      any biological significance. Moreover headless and round-headed spermatozoa could
      be the outcome of the same pathogenetic mechanism.

PMID- 15512186
TI  - Prolapse of pedunculated submucous myoma after insertion of a levonorgestrel
      intrauterine system: two cautionary tales.

PMID- 15512187
TI  - Genital tract metastasis from breast carcinoma.

PMID- 15512188
TI  - Primary thrombocythaemia in pregnancy.

PMID- 15512189
TI  - Torsion of the gravid uterus: an unusual cause of transverse fetal lie.

PMID- 15512190
TI  - Cardiotocography in umbilical cord entanglement.

PMID- 15512191
TI  - Innocuous recurrent vaginal bleeding during pregnancy in a patient with uterus
      didelphys.

PMID- 15512192
TI  - Granulosa cell tumour presenting as an isolated hydrothorax and grossly raised
      CA125.

PMID- 15512193
TI  - Vulvar cancer in pregnancy.

PMID- 15512194
TI  - Endometrial cancer disguised as vulval cancer.

PMID- 15512195
TI  - A pelvic retroperitoneal schwannoma as an adnexal mass.

PMID- 15512196
TI  - Sub-total colectomy for perforated toxic megacolon in pregnancy.

PMID- 15512197
TI  - A case report of a laparoscopically treated cornual pregnancy as a result of
      spontaneous conception after prior salpingectomy for tubal pregnancy.

PMID- 15512198
TI  - Diagnosis and treatment of ruptured splenic artery aneurysm in pregnancy.

PMID- 15512211
TI  - One hundred years of maternity care: the Register of Bagthorpe Workhouse Lying-in
      Hospital 1897-1906.

PMID- 15512212
TI  - Antenatal screening by history taking--a missed opportunity.
AB  - In order to determine how effectively obstetricians and midwives identify and
      manage women at increased risk of fetal abnormality a case note review was
      undertaken. Two district general hospitals in each of two health regions and
      their tertiary referral centres making seven hospitals in all were studied. Women
      booked for antenatal care over a one-year period were included (19 895) which was
      estimated to be 75% of the total. Significant numbers of women at high risk
      because of age, past obstetric, medical or family history were not offered
      appropriate tests such as detailed scanning, carrier status testing,
      amniocentesis or chorion villus sampling. Asian women were less likely to be
      offered screening compared with Caucasians. Women at low risk were subjected to
      inappropriate tests such as amniocentesis. Ultrasound departments were rarely
      informed that a woman had had a previous baby with a structural abnormality. In
      conclusion the quality of booking histories was poor allowing important
      information about past medical, family or obstetric history to be overlooked.
      Maternity units should use carefully structured forms taking when booking
      histories and all staff must have regular training on risk factors.

PMID- 15512213
TI  - Screening for Down's syndrome: experience of two district general hospitals
      having different screening strategies.
AB  - The aim of this retrospective study is to determine the rate of reduction in the
      number of Down's syndrome babies delivered in two hospitals having different
      screening strategies. The total number of Down's syndrome babies during the study
      period was 0.6/1000 births at Birch Hill Hospital and 1.9/1000 births at Oldham
      Hospital. Antenatal diagnosis of Down's syndrome was made in 1/4 of women (25%)
      at Birch Hill and 7/19 of women (37%) in Oldham. The reduction rate of Down's
      syndrome was similar in both hospitals (25 and 26%). This retrospective analysis
      and comparison between two neighbouring units, highlights the fact that there is
      little standardisation of screening policies and screening programmes have not
      resulted in a substantial reduction in Down's syndrome babies.

PMID- 15512214
TI  - Selective use of maternal serum testing.
AB  - Maternal serum testing is used to screen for both trisomy 21 (T21) and structural
      fetal abnormalities such as neural tube defects (NTDs). Second line diagnostic
      testing for T21 is usually by amniocentesis but for NTDs it is simply a detailed
      scan. It is possible that a proportion of women unnecessarily reject both parts
      of the screening test because they would not wish to undergo invasive testing and
      yet would accept a detailed ultrasound scan. This is particularly important in
      maternity units, such as ours, which cannot yet offer detailed fetal anomaly
      scans routinely. A retrospective case-note review of 231 consecutive new bookings
      over a 4-month period identified 61 women who chose initially not to have serum
      measurement of AFP/hCG (double test). Of the 61 women, 23 had rejected serum
      testing because they would not agree to amniocentesis and 29 because they would
      not agree to termination of pregnancy. All 61 women were offered serum screening
      for structural anomalies alone and 21 (34%) then chose to have AFP measurement.
      Maternal serum screening is not a single test and clinicians working in units
      with a limited antenatal ultrasound service should consider offering AFP
      measurement alone to women who decline comprehensive testing.

PMID- 15512215
TI  - The 'Folic Acid Campaign': has the message got through? A questionnaire study.
AB  - There is now clear evidence that folic acid reduces the risk of neural tube
      defects. In February 1996 the Health Education Authority launched a publicity
      campaign to inform women of the benefits of periconceptual folic acid. We have
      surveyed 1000 women to assess the compliance of pregnant women with the
      Department of Health's recommendations about taking folic acid. Of the women, 761
      (76%) said they knew about the benefits of folic acid but only 433 (43%) of them
      took it before pregnancy. Of the 567 women who did not take folic acid before
      conception, 227 had not planned their pregnancy and 239 did not know about the
      benefits. Of the 644 women who planned their pregnancy and knew about the
      benefits of folic acid before conception 211 still did not take folic acid pre
      pregnancy. These findings have important implications for public policy and
      health professionals if the incidence of neural tube defect is to be reduced
      further.

PMID- 15512216
TI  - Eclampsia: a continuing obstetric catastrophe the experience in Ile-Ife, Nigeria.
AB  - All cases of eclampsia over a 15-year period in Ile-Ife University Teaching
      Hospital, Nigeria, were reviewed in order to highlight the problems associated
      with this condition. The incidence was 0.76% of the total deliveries and showing
      increasing trend during the period of study. Nulliparas, mainly teenagers and
      young adults, who were of lower socioeconomic group and who lacked antenatal
      supervision constituted the majority of cases. Many patients presented following
      numerous convulsions. Diazepam in combination with hydralazine were the most
      commonly used drugs. The associated maternal and perinatal mortality and
      morbidity were unacceptably high. Suggestions as to how the incidence might be
      reduced are included.

PMID- 15512217
TI  - Decision-caesarean delivery interval in a Nigerian university hospital:
      implications for maternal morbidity and mortality.
AB  - This is a 5-month prospective study to determine the decision emergency caesarean
      delivery interval in a Nigerian tertiary hospital, the factors responsible for
      the delays and the consequent maternal and perinatal complications. One hundred
      and thirty-four emergency caesarean deliveries were analysed and the main
      indications were failure to progress/ prolonged labour (35.4%), previous
      caesarean-section/failed trial of scar (27.9%), cephalopelvic disproportion
      (26.8%), fetal distress (19.5%), pre-eclampsia/eclampsia (15.3%) and obstructed
      labour/ruptured uterus (14.7%). The mean decision-caesarean delivery interval was
      4.4 +/- 4.2 (SD) hours (range 0.5-26 hours), median 3.2 hours and mode 2 hours.
      Bottlenecks within the maternity unit were responsible for delays in 31.7% of
      cases. Unavailability of paediatrician (19.6%), non-availability of anaesthetic
      coverage (13.6%), unreadiness of the operation theatre (11.9%) and seeking second
      opinion (6.4%) were other major causes of delay. There were 15 perinatal deaths,
      five of whom were directly linked to the delays i.e. a perinatal mortality rate
      of 3.7%. Four maternal deaths were directly attributable to delay, a maternal
      mortality rate of 3%. Other direct consequences of the delays were severe
      haemorrhage (10.3%), uterine rupture (2.3%) and disseminated intravascular
      coagulopathy (1.5%). Suggestions on how to minimise delays in emergency services
      and overall improvement in quality assurance control are discussed.

PMID- 15512218
TI  - Early oral intake after caesarean section performed under general anaesthesia.
AB  - This study assesses the outcome and benefits of initiation of oral intake 4 hours
      after caesarean section done under general anaesthesia. After uncomplicated
      sections, 207 healthy women were alternately assigned either to start oral intake
      4 hours after operation, with concurrent stoppage of infusions (n = 106) or to
      receive 'standard'postoperative care (n = 101). Early oral intake was not
      associated with increase in gastrointestinal morbidity. Compared with the control
      group the early intake group had a shorter mean time to first flatus and to first
      bowel evacuation; initiated breast feeding earlier; ambulated more and were more
      satisfied. Both groups had similar urine output in the first 24 hours. The
      nurse's work load decreased when they looked after the early intake group. It is
      concluded that post-caesarean mothers could be adequately hydrated orally after
      discontinuing infusions in the early postoperative period without apparent harm
      and with benefit.

PMID- 15512219
TI  - Umbilical cord blood gas analysis in augmented labour.
AB  - Labour augmentation with oxytocin may produce an excessive increase in frequency,
      duration or strength in uterine contractions which may result in fetal stress.
      Umbilical cord acid-base assessment provides an objective parameter in evaluating
      the neonatal condition immediately after delivery. We evaluated the neonatal
      condition in 235 deliveries where oxytocin was used for labour augmentation. The
      umbilical cord blood acid-base status was correlated with intrapartum
      cardiotocographic findings and Apgar scores. In two cases we noted umbilical
      artery pH <7.05 but the BDecF was not higher than 11 mmol/l and the 5-minute
      Apgar score was 8 in all cases. Our results indicate that the use of oxytocin for
      labour augmentation had no adverse effects on neonatal condition.

PMID- 15512220
TI  - Vulvar vestibulitis syndrome: a descriptive study and assessment of response to
      local steroid and topical clindamycin treatment.
AB  - Seventy-six women with insertional dyspareunia and clinical features of vulvar
      vestibulitis syndrome (VVS) were followed prospectively. The mean age was 26.4
      years and the mean duration of symptoms prior to attending the department was 2.7
      years. Twenty-nine per cent of women were considered by other clinicians to have
      no physical cause for their symptoms and had been initially referred for
      psychosexual counselling. Most women (53/76) had small, localised areas of
      intoital erythema and tenderness and 15 women revealed, in addition, erythema
      extending on to the posterior fourchette. Eight women had more extensive
      introital erythema associated with a distal vaginitis, some of whom exhibited
      microscopic features suggestive of a desquamative vaginitis in addition to VVS.
      Approximately 20% of women with localised areas of introital erythema and
      tenderness responded to a topical potent steroid or to intralesional injection of
      triamcinolone. Further controlled, long-term follow-up studies using objective
      methods of clinical assessment are urgently needed.

PMID- 15512221
TI  - Practice and perceptions of female genital mutilation among Nigerian Igbo women.
AB  - Genital mutilation occurred in 296 (48.5%) of 610 pregnant Nigerian Igbo women
      attending antenatal clinics. The incidence was especially high in association
      with high maternal age, high parity and low social class. Female genital
      mutilation (FGM) class 1 occurred in 75 (25.3%) cases while FGM class 2 occurred
      in 221 (74.7%). There was no cases of FGM class 3 (infibulation). The majority,
      322 (52.8%) of the women were positively aware of their true genital mutilation
      status, but 288 (47.2%) showed negative response being either unaware of their
      true genital mutilation status or had become confused. Female genital mutilation
      was no longer practised in the locality of 337 (55.3%) of the women, was
      occasionally practised in that of 55 (9.0%) and was still fully practised in that
      of 88 (14.4%) of the respondents. Most of the women, 324 (53.1%) had no knowledge
      of any advantages of female genital mutilation. However, 157 (25.7%) believed
      that it discourages infidelity while 56 (9.2%) believed that it facilitated
      delivery. Similarly, 336 (55.1%) of the women were not aware of any risks of
      female genital mutilation, although 164 (26.9%) believed that it would cause
      difficult labour. Eighty (13.1%) of the respondents would advocate FGM for their
      daughters, out of which 34 (42.5%) cited cultural reasons. Four hundred and sixty
      six women (76.4%) would not wish their daughters to be circumcised. The
      eradication of female genital mutilation must involve the identification of
      issues sustaining the practice in different localities and subsequent action
      supported either by logical persuasion following aggressive health education and
      by legislation.

PMID- 15512222
TI  - Male factors and socioeconomic indicators correlate with the risk of spontaneous
      abortion.
AB  - No less than 10% of clinically recognised pregnancies end as spontaneous
      abortions and the recurrence risk is high. Due to lack of data and appropriate
      study design only little is known about preventable causes of miscarriage. The
      aim of this study was to estimate the effect of paternal and environmental
      factors by studying reproductive histories in population based cohorts. We based
      the study upon two cohorts. The 'abortion cohort' consisted of 55 259 women who
      had a hospitalised spontaneous abortion in Denmark between 1980 and 1992 and who
      had a subsequent non-terminated pregnancy. The 'birth cohort'was based upon a 5%
      random sample of all women who in the same time period gave birth and
      subsequently had a non-terminated pregnancy (11 269 women). Data on change of
      partner, residence, mother's social status or occupation between the two
      pregnancies were linked to these two cohorts using the personal identification
      numbers and information stored in several population registers. Change of partner
      reduced the recurrence risk of spontaneous abortion substantially (OR = 0.59; 95
      CI 0.52-0.67), but also changes in social status or job reduced the recurrence
      risk significantly. Changing the municipality of residence to a low risk area
      (based upon the geographical distribution of spontaneous abortions) reduced the
      risk of spontaneous abortion in both cohorts. A paternal effect on the recurrence
      risk of spontaneous abortion cannot be ruled out but environmental factors also
      play a role.

PMID- 15512223
TI  - Miscarriage: preparing SHOs for their role in hospital care.
AB  - Miscarriage is viewed in the health care system as a minor physical event in
      contrast to the major personal and emotional significance it can have for many
      women. SHOs have an important role in caring for miscarrying women for which they
      receive little preparation. Drawing on the findings from a larger study of
      pregnancy loss this article discusses the issues for SHOs in caring for women who
      miscarry. There is tension between the demands of the health care system, the
      SHO's attitudes and skills and the needs of many women. It is suggested that SHOs
      would be helped when they take up a gynaecological post by the provision of
      information about women's needs. Broadly based discussion should include topics
      such as the system of care, explaining the cause of a miscarriage, disposal
      policy and talking about the remains of the pregnancy.

PMID- 15512224
TI  - The effect of prostanoid precursors and inhibitors on platelet angiotensin II
      binding.
AB  - Pregnancy-induced hypertension is characterised by an imbalance of arachidonic
      acid metabolites: Prostacyclin (PGI2) is vasodilatory and a potent inhibitor of
      platelet reactivity. Thromboxane (TXA2) induces vasoconstriction and platelet
      aggregation. Previous intervention studies have been aimed at increasing
      vasodilatation and decreasing platelet aggregation using low dose aspirin or
      dietary manipulation of prostaglandins. The aim of this study was to investigate
      the value of combining low dose aspirin with dietary fatty acid supplementation
      and its effects on platelet angiotensin II binding in non-pregnant women. Sixty
      non-pregnant, healthy female volunteers were recruited and randomly allocated to
      one of six treatment regimens which included aspirin taken alone and in
      combination with fish oil or evening primrose oil. A control group took no
      treatment. Platelet AII binding was determined before and after treatment for 1
      month. There was no change in platelet angiotensin II binding after 1 month in
      the control group or in those who received evening primrose oil or fish oil
      alone. A significant decrease in binding was found in those who took aspirin in
      combination with fish oil (P = 0.03). An increase in binding was seen in those
      who took aspirin only, although this was not statistically significant (P =
      0.14). A decrease was found in those who took aspirin in combination with evening
      primrose oil but again this was not statistically significant (P = 0.07). This
      study found that the combined effect of low-dose aspirin and fish oil causes a
      significant decrease in platelet angiotensin II binding not caused by either
      compound taken alone. Given that angiotensin II exerts its effect in part by
      direct interaction with vascular AII receptors, (platelets being used as 'models'
      of vascular myocytes), and that pre-eclampsia is associated with major
      pathophysiological changes in prostanoid metabolism, these pilot data provide a
      basis for further investigation.

PMID- 15512225
TI  - Do women referred for colposcopy receive adequate information from the primary
      care team?
AB  - The objective of this study was to assess whether women had been counselled by
      their primary health care team and whether or not they had received any
      information about colposcopy. We also asked where the best information had been
      obtained. The setting was the colposcopy clinic of a large district general
      hospital, the design of which was a cross-sectional audit using a questionnaire.
      The subjects were 100 women attending the colposcopy clinic. The results show
      that 63% of women were seen by their primary health care team before the
      colposcopy visit and that counselling was associated with knowledge about
      colposcopy (P = 0.017). However, 43% of women felt that they knew nothing about
      colposcopy whilst 19% of women thought that the information they had obtained was
      not useful. We conclude that there is scope for improving the quality, timing and
      provision of information for women undergoing colposcopy.

PMID- 15512226
TI  - Cervical cancer--a neglected health tragedy.
AB  - This is a review of the problems of cervical cancer in Nigeria, typified by data
      from a tertiary hospital over a 9-year period. Of 146 cases of cervical cancer
      studied, 79% presented in advanced stages, peak age incidence was between 40 and
      70 years, mean 54.5 +/- 12.4 (SD) years. Squamous cell carcinoma was predominant
      (97% of cases). Presentation was typical: mainly abnormal vaginal bleeding,
      vaginal discharge and postmenopausal bleeding. Low socioeconomic status (90%) and
      high parity (83%) were prominent features. Treatment and outcome were poor
      because of late presentation, lack of radiotherapy facilities and inadequate
      surgical procedures. Comparison with previous Nigerian studies reveal a continued
      lack of improvement over the years as regards preventative strategies and
      adequate treatment facilities. Suggestions on cervical cancer control measures
      for developing countries like Nigeria are given.

PMID- 15512227
TI  - Pulmonary metastases from cervical cancer in Sri Lanka.
AB  - Cervical cancer is the second commonest malignancy in Sri Lankan women. The
      records of 2075 patients treated for cervical cancer from 1989 to 1993 were
      reviewed. Thirty-eight patients (1.8%) developed pulmonary lesions consistent
      with metastases. The median age at the time of presentation with metastases was
      49.8 (range 24-73) years. Ten patients (26.3%) had pulmonary metastases at
      presentation. Twenty-eight (73.7%) developed metastases during follow-up. By the
      end of 2 years 27 (96.4%) of these patients had developed pulmonary metastases.
      The median time from diagnosis of cervical cancer to the detection of pulmonary
      metastases was 9 months. The commonest histological cell type was the large cell
      non-keratinising squamous carcinoma. Nine (23.7%) of these patients were
      asymptomatic. Two patients had lung metastases on initial staging chest X-ray
      while the other seven were detected during routine 3-monthly surveillance chest X
      rays as follow up of primary treatment. This emphasises the importance of
      incorporating routine surveillance chest X-ray as part of the regular follow up.
      All patients with pulmonary metastases had abnormal shadows in chest X-rays.
      Nodular lesions were the commonest radiological findings. Local disease was
      controlled in 17 (55.3%) of the patients who developed metastases during follow
      up, while 11 (28.9%) had active disease. There were 24 patients with spread to
      other sites at the time of diagnosis of pulmonary metastases. The discovery of
      effective chemotherapy agents is anticipated.

PMID- 15512228
TI  - A multivariate approach in statistical analysis for perinatal research: Cox
      regression analysis.

PMID- 15512229
TI  - Myotonic dystrophy in pregnancy.

PMID- 15512230
TI  - HELLP syndrome at 21 weeks' gestation in association with trisomy 13.

PMID- 15512231
TI  - Postpartum ovarian vein thrombosis with massive inferior vena cava thrombus
      formation.

PMID- 15512232
TI  - Klippel-Trenaunay-Weber syndrome in pregnancy and at delivery.

PMID- 15512233
TI  - Triplet pregnancy with complete hydatidiform mole coexisting with two fetuses.

PMID- 15512234
TI  - A twin pregnancy in a uterus didelphys.

PMID- 15512235
TI  - Incarcerated retroverted uterus--a non recurring complication of pregnancy.

PMID- 15512236
TI  - Sciatic nerve tumour masquerading as pregnancy related back pain.

PMID- 15512237
TI  - In situ squamous cell carcinoma of the endometrium associated with long-term
      intrauterine device (Dalkon Shield) usage.

PMID- 15512238
TI  - Uterine sarcoma: an unusual metastatic site.

PMID- 15512239
TI  - Plasma cell vaginitis--a new clinical entity?

PMID- 15512240
TI  - Sarcoma botryoides in a seven year old: successful chemotherapeutic management.

PMID- 15512241
TI  - Double vulva.

PMID- 15512242
TI  - A dilated cervical crypt as a cause of uterine enlargement.

PMID- 15512243
TI  - The use of methotrexate in ectopic pregnancy with fetal cardiac activity.

PMID- 15512244
TI  - Persisting menorrhagia after successful thyroxine replacement in a hypothyroid
      patient.

PMID- 15512247
TI  - Management of fetal alloimmune thrombocytopenia-a less invasive option?
AB  - Fetal alloimmune thrombocytopenia (FAITP) is a condition associated with
      significant infant morbidity and mortality. We report on the West of Scotland
      experience of 30 pregnancies complicated by FAITP over a 17-year period (1982
      98). Management options included serial cordocentesis together with platelet
      transfusion, and maternal intravenous gammaglobulin (IVIgG) therapy. Of those
      pregnancies managed by serial cordocentesis all had poor outcomes. Weekly IVIgG
      was administered to the remaining pregnancies, all of which had a good outcome
      although four infants were thrombocytopenic at birth. None of these cases had
      previously been complicated by intracranial haemorrhage. In the milder end of the
      spectrum of FAITP we would suggest that IVIgG is an alternative treatment option.

PMID- 15512248
TI  - Laparoscopic evidence of upper genital schistosomiasis.
AB  - This prospective study aimed at estimating the proportion of upper genital
      schistosomiasis in patients submitted to video-assisted laparoscopy and to
      describe carefully the bilharzial lesions seen at laparoscopy. Four hundred and
      thirty-four patients submitted to videolaparoscopy were included in this study.
      The pelvis was carefully explored for evidence of recent or old upper genital
      tract chronic inflammation. Suspicious areas like nodules, masses, vascular
      lesions, adhesions, pathologic tubes or ovarian cysts were biopsied. Positive
      cases of schistosomiasis were submitted to a thorough immunological evaluation.
      Diagnostic laparoscopy was carried out in 185 cases while the remaining patients
      required operative intervention. Biopsy was taken from 128 cases (29.8%) which
      revealed schistosomiasis in four cases only (0.9%) who demonstrated high titre of
      antibodies against Schistosoma haematobium . Despite being a rare disease, upper
      genital schistosomiasis should be considered as a possible cause in all cases of
      adhesions, tubal, peritoneal or ovarian lesions, if the patient comes from an
      endemic area.

PMID- 15512249
TI  - Fetal magnetoencephalogram recordings and Fourier spectral analysis.
AB  - This study investigates the fetal brain activity in normal and pre-eclamptic
      pregnancies. Measurements were performed by means of a Superconducting Quantum
      Interference Device (SQUID) in an electrically shielded room of low magnetic
      noise. The study was prospective. Eleven pregnant women with pre-eclampsia and 21
      normal pregnancies were included. All were at 37-40 weeks of pregnancy.
      Biomagnetic signals (waveforms), recorded from the fetal brains in the frequency
      range of 2-7 Hz, were expressed in terms of magnetic power spectral amplitudes.
      These were low (mean, 376.67; SD, 28.66) in almost all normal pregnancies, and
      high (mean, 554.91; SD, 149.56) in most pregnancies complicated with
      preeclampsia. These findings were of statistical significance (Student's t -test,
      P < 0.005). Biomagnetic measurements of fetal brain activity is a promising
      screening procedure for assessing the cerebral function, especially in high risk
      pregnancies.

PMID- 15512250
TI  - The incidence of maternal dental treatment during pregnancy.
AB  - A questionnaire was given to women who had delivered a live baby to assess their
      knowledge and uptake of dental treatment during their recent pregnancy of the 496
      women surveyed, 95% knew that dental treatment was free on the National Health
      Service for 1 year after that pregnancy. Despite a high level of knowledge in
      this area, 64% underwent a dental check-up during pregnancy and of those women
      who had a check-up 27% had dental restorations placed in their teeth during that
      pregnancy. Only 26% of women were advised to see a dentist by a health
      professional. The exact incidence of dental treatment during pregnancy is not
      known, however, if our area is typical of the United Kingdom, large numbers of
      women are undergoing dental treatment during pregnancy and the contribution that
      this makes to maternal and fetal health should be studied.

PMID- 15512251
TI  - Shoulder dystocia: room for improvement?
AB  - A questionnaire was completed by 166 midwives and obstetric junior doctors to
      assess their knowledge of the management of shoulder dystocia and to establish
      whether mandatory teaching and updating is required. Ninety-six participants
      (58%) claimed they were confident in the management of shoulder dystocia.
      However, only six (4%) respondents gained full marks on the scoring system
      devised to assess their knowledge. Furthermore 36 (22%) of those surveyed
      suggested rotation of the shoulders to the anterior-posterior position to
      alleviate the dystocia and 32 (19%) proposed pulling the head hard. Although
      there are limitations in assessing competence by the use of a questionnaire, the
      results of this survey suggest that there is considerable room for improvement.
      We suggest that a shoulder dystocia drill is introduced to all labour wards in
      the United Kingdom so that birth attendants can develop and memorize a sequence
      of procedures to use when confronted with this life-threatening emergency.

PMID- 15512252
TI  - Increased rate of small-for-gestational-age neonates in pre-eclamptic women with
      preterm deliveries.
AB  - We sought to determine whether hypertensive pregnancies can be considered a
      distinct subgroup of premature births. All women in our centre who had had
      singleton preterm spontaneous deliveries over an 8-year period were divided into
      hypertensive and normotensive groups and compared for maternal characteristics
      and neonatal outcome. Of the 4175 eligible women, 9.8% (n = 410) had pre
      eclampsia. These patients had higher rates of small-for-gestational-age neonates
      (19%, 78/410), abruptio placenta (7.8%, 32/410) and caesarean section rate
      (52.7%, 216/410) than the normotensive women (4.3%, 158/3765; 4.6%, 172/3765; and
      19.6%, 739/3765, P < 0.001, respectively. The rate of preterm premature rupture
      of membranes was significantly lower in the hypertensive than in the normotensive
      group (5.9% vs. 17%, respectively; P < 0.001). We concluded that hypertensive
      women who deliver prematurely belong to a subgroup with particular
      characteristics. The increased rate of small-for-gestational-age neonates in pre
      eclamptic women suggests that reduced uteroplacental perfusion may cause fetal
      growth impairment before the onset of the hypertensive disorder.

PMID- 15512253
TI  - Caesarean myomectomy--a safe procedure. A retrospective case controlled study.
AB  - Sixteen women, with uterine fibroids in pregnancy, who were treated by caesarean
      myomectomy, were compared retrospectively with 16 women, without uterine fibroids
      who had caesarean section during the same period. Myomectomy was performed at
      caesarean section after delivery of the baby and the placenta, with the
      administration of intravenous oxytocin. The fibroid defects were occluded with
      continuous interlocking and fixed sutures. Routine caesarean section was
      performed on the subjects in the control group. The comparative efficacy of the
      procedure was measured by comparing pre- and post-operative haemoglobin levels,
      measured blood loss, need for blood transfusion, post-operative febrile morbidity
      and length of hospital stay in both groups. Caesarean myomectomy resulted in a
      mean blood loss of 495 ml (range 200-1000 ml) compared with 355 ml (range 150-900
      ml) in the control group (P =0.907). The caesarean myomectomy group had a mean
      fall in haemoglobin level of 1.7 g/dl compared with a fall of 1.4 g/dl in the
      control group. There were no significant differences between the groups in the
      need for blood transfusion, post-operative febrile morbidity or length of
      hospital stay. The results indicate that caesarean myomectomy is safe and offers
      no significant increased risk to the patient over caesarean section alone. This
      is beneficial to the health sector by the avoidance of an interval myomectomy
      hence justifying the cost effectiveness of the procedure.

PMID- 15512254
TI  - Delaying planned caesarean delivery until 39 completed weeks of gestation: the
      experience of a district general hospital.
AB  - In recent times, it has become clear that delaying elective caesarean delivery
      until 39 completed weeks of pregnancy decreases neonatal respiratory morbidity.
      It is uncertain if such a policy would result in a higher emergency caesarean
      section rate and possible increased maternal morbidity. This retrospective review
      of the first year of adopting such a policy, involving 258 planned elective
      caesarean deliveries, showed that there was no significant increase in emergency
      caesarean section rate (P > 0.10). Those who had to be delivered by emergency
      caesarean section had the same benefit of having epidural/spinal anaesthetic for
      their delivery, and no major complication when compared with those who had
      elective caesarean delivery as planned. There is no evidence that delaying
      elective caesarean delivery until 39 completed weeks of gestation results in
      adverse maternal outcome.

PMID- 15512255
TI  - The role of forceps in modern obstetrics.
AB  - The objective of this study was to assess the safety and devise criteria to
      minimise complications following forceps deliveries. A prospective analytical
      study was performed on 644 consecutive forceps deliveries in a Sri Lankan
      provincial hospital. The incidence of maternal and fetal complications was
      analysed. The incidence of both cervical and third degree perineal tears was
      commoner in face-to-pubis deliveries. When the number of traction efforts
      required to complete the delivery is more than three the incidence of third
      degree perineal tears and postpartum haemorrhage became significantly commoner.
      There were six cases of ruptured uterus and all were in multiparous patients
      following mid-cavity forceps deliveries. The maternal and fetal morbidity
      following rotational forceps deliveries was no different from non-rotational
      forceps deliveries. In addition to the standard criteria of head being fully
      engaged in the pelvis, cervix being fully dilated, the station of the head below
      the level of the ischeal spines and bladder being empty before attempting forceps
      delivery, we also recommend that the baby should be delivered occipito-anterior
      and the number of traction efforts used to be kept at three or less to minimise
      the maternal trauma.

PMID- 15512256
TI  - Diagnosis of ruptured fetal membranes in pregnancy with the use of urograffin.
AB  - The objective of our study was to assess the value of intraamniotic injection of
      urograffin in the diagnosis of premature rupture of membranes (PROM). Intra
      amniotic injection of urograffin with the concomitant insertion of a vaginal
      tampon was performed in 30 consecutive patients who were admitted because of
      suspected PROM and the presence of a heavy bloody vaginal secretion. The vaginal
      tampons were X-rayed for the presence of radio-opacity. In 23 patients, traces of
      urograffin were found in the vaginal tampons by X-ray. No fetal or maternal
      complications were observed during delivery and puerperium. We suggest the use of
      intraamniotic injection of urograffin for the diagnosis of PROM in cases where
      heavy bloody vaginal discharge is present.

PMID- 15512257
TI  - Transvaginal and transabdominal ultrasound for the diagnosis of placenta praevia.
AB  - This randomised prospective study was designed to evaluate the use of
      transvaginal (TVS) and transabdominal (TAS) ultrasound in the diagnosis of
      placenta praevia and its effect on length of stay in hospital. One hundred and
      thirty patients with antepartum haemorrhage (APH) and/or malpresentation with a
      suspicion of placenta praevia were referred to the scanning department of
      Aberdeen Maternity Hospital and Princess Badee'a Teaching Hospital from July 1993
      to December 1996. Fifty-eight patients had an ultrasound because of antepartum
      haemorrhage and 72 had a malpresentation and/or unstable lie. All examinations
      were performed by the same authors. Placenta praevia was diagnosed in 13 (22.4%)
      out of 58 cases presenting with APH and in five (7%) out of 72 cases presenting
      with malpresentation. There was a high false positive rate in the detection rate
      of placenta praevia using TAS (23%) compared with TVS (11.5%) which is higher
      than other reported figures (2-6%). The mean length of stay in hospital of the
      group in whom the results were released was 9.2 days compared with those not
      released where it was 15.7 days. The difference was significant (P <0.05). This
      study suggests that the traditional transabdominal approach to the diagnosis of
      placenta praevia can be improved upon. TVS is a safe method and with improved
      accuracy over TAS can reduce the length of stay in hospital.

PMID- 15512258
TI  - Abdomino-pelvic packing to control severe haemorrhage following caesarean
      hysterectomy.
AB  - Surgically uncontrollable peri-operative obstetric haemorrhage associated with
      coagulopathy, developed in five women who were managed by emergency caesarean
      hysterectomy. All women had a morbidly adherent anterior placenta praevia and a
      previous lower segment caesarean section scar. Conventional medical and surgical
      therapy to control bleeding from pelvic and abdominal raw surfaces were
      unsuccessful. Abdomino-pelvic packing was performed with 10-12 dry laparotomy
      pads applied firmly over bleeding sites. The abdomen was closed after observation
      of the cessation of bleeding for 5-10 minutes. Following correction of
      coagulation and haemodynamic disorders relaparotomy for pack removal was
      performed 34-48 hours later. One patient developed small bowel obstruction on the
      5th post-operative day, however, there was no long term gynaecological morbidity
      in any of the cases. Abdomino-pelvic packing achieved complete haemostasis in all
      of the five women which we believe may have been impossible using alternative
      measures.

PMID- 15512259
TI  - A comparison between ultrasound and clinical methods for predicting fetal weight.
AB  - Fetal weight prediction by different methods were compared. Those methods were
      ultrasound fetal weight estimations using Campbell, Warsof and Hadlock equations,
      and clinical subjective estimation by experienced obstetricians, as well as
      clinical objective studies (Zayed's equation). We evaluated 523 Jordanian
      (Arabic) patients in labour. Our results shows that ultrasound equation provides
      the highest accuracy in predicting fetal weight. In this study Hadlock's equation
      was more precise than the other equations. There is still a place for clinical
      fetal weight estimation, especially if objection methods are used.

PMID- 15512260
TI  - Idiopathic hypoparathyroidism-two successful pregnancies despite uncontrolled
      hypocalcaemia.

PMID- 15512261
TI  - Laparoscopic assisted vaginal hysterectomy--190 cases: complications and
      training.
AB  - Laparoscopic assisted vaginal hysterectomy continues to gain popularity worldwide
      without evidence from any controlled trials of its superiority over existing
      techniques. There is some concern over complication rates particularly damage to
      the urinary tract and haemorrhage. The Royal College of Obstetricians and
      Gynaecologists has compiled a register of preceptors for advanced laparoscopic
      surgery, however there is nothing to prevent a surgeon without adequate training
      or experience from embarking upon any form of minimal access surgery. This series
      consists of 190 cases performed by one surgeon in a District General Hospital
      over the past five years. The mean operating time was 87 minutes and the mean
      hospital stay 2.7 days. There were nine failures. The incidence of late urinary
      tract damage was 1.6% and haemorrhage requiring transfusion 3.7%. Both the
      complication and failure rate fell slowly with experience, implying that the
      surgical learning period is significantly longer than with conventional surgery.
      With better selection it is felt that these figures can be further improved.

PMID- 15512262
TI  - Audit of the views of gynaecological cancer patients regarding follow-up.
AB  - The purpose of this study was to audit patients opinions on routine follow-up and
      discharge from the gynaecology clinic. The setting was the gynaecology clinic of
      a large district general hospital and the design was a cross-sectional audit
      analysis using a written questionnaire. The subjects were 103 women attending the
      gynaecological out patients for review following previous treatment for various
      gynaecological cancers. Ninety patients took part in the study, of these 36 (40%)
      wished for 'free access', 29 (32%) wished for routine hospital follow-up, and 25
      (28%) wished for discharge but with follow-up by their general practitioner.
      There were no statistically significant differences in choices between cancer
      groups. The choice of 'free access'seemed to be an important choice for women. We
      conclude that routine hospital follow-up of women treated for gynaecological
      cancer is not the desire of the majority and it appears the women may have
      different inherent psychological characteristics.

PMID- 15512263
TI  - A comparative study of the assessment of cervical intraepithelial neoplasia in
      women having large loop excision of the transformation zone.
AB  - Findings on Papanicolaou (Pap) smear and colposcopically directed punch biopsy
      show discrepancies when compared with findings on loop excision specimens and
      this situation creates management problems. We performed a comparative assessment
      of cervical intraepithelial neoplasia (CIN) in 100 consecutive women who had
      large loop excision of the transformation zone (LLETZ) with a view to developing
      a local protocol that would be safe, avoid delay and minimise over-treatment.
      Agreement between Pap smear and LLETZ was 62% with 21% overcall and 17% undercall
      at Pap smear; there was no significant correlation (Spearman's rank correlation
      coefficient 0.17 P > 0.05). The agreement between punch biopsy and LLETZ was 61%
      with 25% overcall and 15% undercall at punch biopsy; there was a slight agreement
      over chance (kappa=0.20) and there was a weak but significant correlation
      (Spearman's rank correlation coefficient=0.26; P = 0.047). Colposcopic impression
      of 'highly abnormal'lesions agreed with high grade lesions on LLETZ in 83% of
      cases. The problem of undercall suggests that defaulters with apparent low grade
      dyskaryosis need to be pursued to colposcopy as vigorously as defaulters with
      high grade dyskaryosis. The lack of significant correlation between cervical
      cytology and LLETZ finding suggests that the smear-to-colposcopy waiting interval
      should not be strictly based on the degree of dyskaryosis.

PMID- 15512264
TI  - Self-reported cervical screening practices and beliefs of women from urban, rural
      and remote regions.
AB  - This survey aimed to explore women's perceptions of a number of issues relating
      to the availability and utilisation of cervical cancer screening services in the
      rural, remote and urban regions of New South Wales (NSW) Australia. The survey
      involved urban, rural and remote regions of NSW determined by the definition of
      the Department of Community Services and Health. This was a cross-sectional
      telephone survey. Of the 339 eligible urban households, 265 (78%) completed
      interviews; of the 286 eligible rural households, 238 (83%) completed interviews;
      of the 285 eligible remote households, 230 (81%) completed interviews. Telephone
      contact was made with randomly selected households in each region. Women in the
      households were asked to complete a computer-assisted telephone interview. The
      survey addressed a number of issues relating to cervical screening: cervical
      cancer risk status; provider of Pap smear service; distance travelled to have a
      Pap smear; perceived barriers and facilitators to cervical screening. There was
      no statistically significant difference in the proportions of women from urban
      (74%), rural (76%), and remote (71%) regions who reported having a Pap smear in
      the 2 years preceding the survey. General practitioners provided the majority
      (more than 70%) of tests irrespective of region. Compared with women from urban
      areas, women from rural and remote areas were almost twice as likely to have had
      their last Pap smear from a male general practitioner. A greater proportion of
      women from remote regions had to travel for 60 minutes or more to access
      providers of Pap smear services. Few differences in the top three reported
      barriers to, and facilitators for screening were evident between regions and
      between those women who had and had not been adequately screened. Issues of
      distance, isolation and access to alternative service providers are a concern to
      women in rural and remote regions and should be considered by those involved in
      the implementation of cervical cancer screening services.

PMID- 15512265
TI  - Self-assessment of morbidity following radical hysterectomy for cervical cancer.
AB  - The aim of this study was to assess the magnitude of the morbidity following
      radical surgery for early stage cervical cancer. We performed a retrospective
      survey of all women who had undergone a radical hysterectomy and lymphadenectomy
      between the months of July 1995 and December 1996 inclusive at either the Royal
      Marsden or St George's Hospital (n =38), using a detailed questionnaire on
      bladder, ano-rectal and sexual function, both before and after treatment. Sixteen
      women (44.4%) received adjuvant radiotherapy. The mean interval between surgery
      and inquiry was 16.4% months (range 8-25 months). The mean age at the time of
      surgery was 40.5 years. Thirty-six out of 38 women contacted responded (94.7%).
      Overall 33 women (91.7%) reported new bladder, ano-rectal or sexual symptoms.
      Complaints of urinary incontinence, particularly of urge incontinence, and of
      voiding difficulties increased significantly after surgery (P <0.05). However,
      only 5.3% of women had sought treatment. Tenesmus increased significantly (P
      <0.05), while increases in diarrhoea and faecal incontinence were not
      statistically significant (P =0.051). Although 12.9% of women stated an
      improvement in their sex lives, 54.8% thought that their sex life was worse after
      treatment, and 12.9% of women had ceased sexual activity altogether. Of women of
      childbearing age 53.8% felt adversely affected by their loss of fertility.
      Bladder, ano-rectal and sexual symptoms are very common following radical
      hysterectomy for cervical cancer, with adverse effect on quality of life, and
      persist into the second year after treatment.

PMID- 15512266
TI  - Effects of hormone replacement therapy on serum lipids and phospholipids in
      postmenopausal women.
AB  - Hormone replacement therapy (HRT) has been shown to reduce the risk of
      cardiovascular disease and the beneficial effects may be mediated in part by
      favourable changes in plasma lipid levels. Evidence exists concerning the effect
      of combined oestrogen and progestogen on lipids, nevertheless no such evidence
      can be found on the phospholipid profile, which is important the lipid metabolic
      pathways. In the present study, involving the serum lipids and lipoproteins, we
      observed an increase in the concentration of total cholesterol (P < 0.001), HDL-C
      (P < 0.001), HDL-C (P < 0.001), 2 HDL-C (P < 0.001) and a decrease in the ratio
      LDL-C/ 3 HDL-C (P < 0.001) in the subjects of Group B (oestrogen plus
      progestogens) compared with controls (baseline). Also, we found an increased in
      triglycerides (P < 0.01) and ApoA-1 (P < 0.01) concentrations in the subjects of
      Group A (oestrogen alone) compared with controls (baseline). With regard to the
      phospholipids, the main changes observed in their concentrations were: an
      increase in phosphatidyl choline (P < 0.001) and a decrease in phosphatidyl
      serine (P < 0.01) for both groups compared with controls. Also, a decrease in
      phosphatidylinositol (P < 0.01) in Group B compared with controls (baseline). The
      significance of these results are discussed.

PMID- 15512267
TI  - Repeat oestradiol implants: features of dependence?

PMID- 15512268
TI  - Intrauterine pregnancy complicated by placenta accreta after previous
      transcervical resection of endometrium.

PMID- 15512269
TI  - Fetal subaponeurotic haemorrhage following maternal trauma.

PMID- 15512270
TI  - Warfarin anticoagulation in pregnancy complicated by antiphospholipid antibody
      syndrome and heparin allergy.

PMID- 15512271
TI  - Massive secondary postpartum haemorrhage three weeks after caesarean section.

PMID- 15512272
TI  - Massive intraperitoneal haematoma following caesarean hysterectomy treated by
      aspiration.

PMID- 15512273
TI  - The use of intrapartum fetal pulse oximetry in the presence of fetal cardiac
      arrhythmia due to a cardiac tumour.

PMID- 15512274
TI  - Surviving twins delivered at 29 weeks' gestation following abortion of one
      triplet at 15 weeks and rescue cervical cerclage.

PMID- 15512275
TI  - Congenital rhabdomyosarcoma of maxillo-facial region associated with
      polyhydramnios.

PMID- 15512276
TI  - Hirschsprung's disease: an unusual presentation in pregnancy.

PMID- 15512277
TI  - Vulvovaginitis secondary to examination with latex rubber gloves.

PMID- 15512278
TI  - Cystodistension for detrusor instability--how much distension?

PMID- 15512279
TI  - High-grade endometrial stromal sarcoma (HG-ESS) in an adolescent girl with benign
      mediastinal Schwannoma.

PMID- 15512281
TI  - Recurrent haemoperitoneum of ovarian origin complicating anticoagulant therapy.

PMID- 15512280
TI  - A case of endometrial stromal cell tumour with ovarian sex-cord-like
      differentiation.

PMID- 15512282
TI  - Massive corpus luteum haemorrhage--still a complication of anticoagulant therapy
      despite recent less intense regimens.

PMID- 15512285
TI  - Postgraduate journal club as a means of promoting evidence-based obstetrics and
      gynaecology.
AB  - We assessed the feasibility of a new educational programme to teach critical
      appraisal of the medical literature to postgraduate trainees. The new programme
      used a journal club format where selection of topics and articles was driven by
      clinical problems arising in day-to-day practice. Papers were appraised
      critically according to validated guidelines using computer software for
      appraisal, electronic storage and retrieval. Over the initial 4-month period the
      journal club produced 17 critically appraised topics, two of which were published
      in peer-reviewed journals. During the study, trainees' reading time improved from
      a median of 2.0 hours (range 1-5 hours) to 3.5 hours (range 2-8 hours) (P =
      0.026) and their knowledge scores improved from a mean of 50.8 (SD 4.0) to 62.9
      (SD 4.3) (P = 0.003). We conclude that a journal club supported by electronic
      means of critical appraisal and dissemination of appraised information can be
      used to encourage the practice of evidence-based medicine.

PMID- 15512286
TI  - An open trial comparing isradipine with hydralazine and methyl dopa in the
      treatment of patients with severe pre-eclampsia.
AB  - Placental blood flow is decreased in pre-eclampsia and is worsened by decreasing
      blood pressure. Hydralazine, which causes vasodilatation, does not affect
      placental bed vessels. Calcium channel blockers (like isradipine) are
      vasodilators that do affect placental bed vessels and should improve blood flow
      even while decreasing blood pressure. The aim of the study was to determine if
      isradipine (parenteral and oral) was better than parenteral hydralazine and oral
      methyl dopa in severe pre-eclampsia in achieving better control of blood
      pressure. The study was a prospective randomised trial performed at The
      University Hospital of the West Indies. The sample consisted of 39 women with
      severe pre-eclampsia. Variables examined consisted of blood pressure before and
      after treatment, the increment in gestational age at delivery related to
      treatment, fetal Apgar score and birth weight. There were no significant
      differences in any of these variables between the two groups. Isradipine was as
      effective as hydralazine in reducing maternal blood pressure and in prolonging
      pregnancy.

PMID- 15512287
TI  - Perinatal litigation in Scotland 1980-1995: its incidence, rate and nature.
AB  - Many claims about an increase in the incidence of perinatal litigation have been
      made, despite a lack of comprehensive data which might confirm this. A large
      scale study into litigation throughout Scotland from 1980 to 1995 revealed an
      initial sharp rise in the number of claims, but a fall in the overall number of
      claims made in 1994 and 1995; a similar picture was noted in a limited cross
      border examination of English files. Not every area has experienced a reduction
      in incidence, and the rate of litigation (measured in deliveries per legal claim)
      varied hugely over time and between areas. A wide variety of head of claim was
      noted. Twenty-one percent of Scottish claims concerned cerebral palsy; of closed
      claims only 15% were successful, but a large proportion are still on-going. While
      the 'litigation crisis' is difficult to verify from these data, costs appear to
      be rising.

PMID- 15512288
TI  - Interprofessional and peer criticism: a side-effect of litigation?
AB  - Claims about a rising litigation rate, particularly in obstetrics, have allegedly
      fuelled fears of worsening relationships between obstetricians and midwives.
      Interviews with a number of practitioners, and others concerned with medical
      litigation, provided differing views about these assertions. While the fear of
      litigation is one element, it is probable that other often personal-factors may
      play a part. The overall tone of the interviews, however, suggested a significant
      degree of tension between obstetric and midwifery practitioners. The changing
      role of the midwife in contemporary maternity care also brings fresh challenges
      in developing healthy inter-professional relationships. At a time when litigation
      is believed to be ever-increasing, the existence of poor work relationships in
      this multi-disciplinary field may be critical.

PMID- 15512289
TI  - Pregnant women of 35 years of age or more: maternal serum markers or
      amniocentesis?
AB  - The aim of this prospective study was to compare triple test screening (alpha
      fetoprotein, beta-chorionic gonadotrophin and unconjugated oestriol) with
      amniocentesis in the detection of fetuses with Down's syndrome in women of 35
      years of age or more. Between 1992 and 1996, maternal serum markers were
      evaluated in 1406 women who had amniocentesis for prenatal diagnosis of
      chromosomal abnormalities related to a maternal age of 35 or more years. Sixteen
      fetuses with Down's syndrome were identified in the whole group by amniocentesis
      and karyotyping. The group with negative triple test screening consisted of 919
      pregnancies and included two fetuses with trisomy-21 (false negatives). With
      triple test screening in the age group over 35, there was a detection rate of
      87.5% for cut-off points ranging from 1:200 up to 1:350, with corresponding false
      positive rates ranging between 23% and 34%. In our population, if we had
      practiced the policy of offering amniocentesis only to women screening positive
      for the ages of 35 and 36 and to all pregnant women of 37 or more, we would have
      carried out 30% less amniocenteses. In this group of 1406 women, 33 abnormal
      karyotypes were detected with amniocentesis (16 Down's syndrome included) and
      equal number of elective abortions were carried out. Nevertheless, 19 healthy
      fetuses and neonates were lost after amniocentesis. Considering the high
      detection rates that can be achieved with triple test screening, the existing
      procedure related risk of amniocentesis (0.5-1.0%), and the facts that conception
      in women over 35 years of age is usually more difficult and the background loss
      usually higher than in younger women, we believe that in the future women over 35
      should be offered a choice between non-invasive and invasive procedures after
      being thoroughly informed.

PMID- 15512290
TI  - The outcome of five years' implementation of maternal serum screening for Down's
      syndrome comparing actual age risks and mode of delivery.
AB  - In this paper 13 613 triple test results from the period 1992- 1997 were
      analysed. The probability of receiving a high risk result for Down's syndrome
      from a serum screen, related to the patient's age, was calculated. The modes of
      delivery of the patients receiving a high risk result were also compared with the
      rest of the population. The probability of receiving a high risk result increased
      from 1.2% at 25 years of age to 43.9% at 40 years of age. There was a decrease in
      the likelihood of having operative intervention at delivery amongst the high risk
      group but this did not reach statistical significance. This highlights the need
      for accurate information in risk and probability when counselling a patient
      undergoing serum screening. Patient's anxiety relating to mode of delivery may
      also be alleviated by knowing they have no greater risk of operative delivery.

PMID- 15512291
TI  - Meconium-stained amniotic fluid in term pregnancies-a clinical view.
AB  - The objective of this study was to explore details of the clinical relationship
      between meconium-stained amniotic fluid (MSAF) in labour, abnormal fetal heart
      pattern and meconium aspiration (MA). This was a prospective study carried out in
      Princess Badeea Teaching hospital during a 6-month period from March to September
      1997. During the study period 344 (8.5%) of the deliveries had MSAF (344 women).
      Continuous fetal heart monitoring was routinely used and 36 women with MSAF
      (10.5%) needed to be delivered by caesarean section because of fetal distress
      (diagnosed by abnormal fetal heart pattern) in early labour, compared with 0.95%
      in those with clear amniotic fluid (CAF), (P <0.00001). Many infants in the MSAF
      group had a low Apgar score and required ventilation at birth. Nineteen infants
      (5.5%) developed MA, three of whom (15.8%) died. We conclude that there is an
      association between MSAF, abnormal fetal heart pattern in labour and a low Apgar
      score and that it should be considered a high risk situation. MA a problem that
      occurs with particulate meconium was significantly related to abnormal fetal
      heart pattern and longer length of labour.

PMID- 15512292
TI  - Predictive value of transvaginal ultrasonography for determining the response to
      tocolytic therapy in cases with preterm labour.
AB  - This study was performed prospectively on 144 randomly selected women carrying
      singleton uncomplicated pregnancies of 20 to 36 gestational weeks and 60 women
      with preterm labour matched for gestational age to determine the predictive value
      of transvaginal cervical measurements for evaluation of the response to tocolytic
      therapy. Cervical length and width and width of the cervical canal were measured
      and funnelling of internal os of the cervical canal was evaluated by transvaginal
      ultrasonography in each case. These measurements did not reveal any change
      depending on the gestational age in the control group. The mean values for
      cervical length and width, and width of cervical canal were 45.05+/-6.52 mm,
      38.75+/-4.11 mm, 7.01+/-2.76 mm, respectively. Mean cervical length+/-standard
      deviations of the control group were used as cut-off values for the prediction of
      preterm delivery in the preterm labour group. When the cut-off value of the
      cervical length was accepted as 38.53 mm (-1 SD of the control group), the
      sensitivity, specificity, positive and negative predictive values for prediction
      of preterm delivery were 80.9%, 72.2%, 87.2%, 61.9%, respectively; whereas when
      this cut-off value was used in combination with the funnelling of the internal
      cervical os, the sensitivity and negative predictive value decreased to 40.5% and
      41.9%, respectively; but the positive predictive value and specificity became
      100.0% and 100.0%, respectively.

PMID- 15512293
TI  - A pilot study of the use of a low oxalate diet in the treatment of vulval
      vestibulitis.
AB  - Thirty-one women with vulval vestibulitis were evaluated for evidence of abnormal
      dietary oxalate intake and a wide range of dietary intakes was recorded. No woman
      was found to have abnormal urinary excretion. Sixteen women agreed to undertake a
      low oxalate diet and there was an apparent response in six (37%).

PMID- 15512294
TI  - The joint vulval clinic: a review of the first three years.
AB  - This aim of this study was to undertake a retrospective analysis of the notes of
      all new patients who attended the joint vulval clinic between 1994 and 1997. One
      hundred and forty-five patients were seen, and data analysed for 133 (92%). The
      study identified the range of diagnoses seen; treatment modalities undertaken;
      and enabled comparisons to be made between our findings and those of other
      workers.

PMID- 15512295
TI  - Towards the modern management of ectopic pregnancy: a complete audit cycle of
      practice in a London teaching hospital.
AB  - We carried out a complete audit cycle of the management of ectopic pregnancy at a
      London teaching hospital over 2 years. Case notes of women presenting to St
      George's Hospital, London in 1995 with ectopic pregnancy were examined and
      management was assessed. The targets were low rates of rupture, high rates of
      sonographic diagnosis of ectopic pregnancy, acceptable rates of tubal
      conservation and laparoscopic surgery. We also considered levels of training of
      junior doctors in laparoscopic surgery for ectopic pregnancy and the acceptable
      duration of hospital stay for patients. Recommendations were made, the standards
      were modified, and the audit repeated for the year 1996. A substantial
      improvement in the quality of care of women with ectopic pregnancy was achieved.
      The main improvement was in the ultrasonographic diagnosis of ectopic pregnancy.
      There was also a reduction in ectopic pregnancies which were ruptured, possibly
      due to earlier diagnosis. The percentage of cases treated laparoscopically
      remained stable. More junior doctors performed laparoscopic surgery for the
      condition. Finally, we confirmed that laparoscopic management of ectopic
      pregnancy significantly reduces duration of hospital stay, conferring advantages
      to both patient and hospital.

PMID- 15512296
TI  - The use of non-linear analysis for differentiating the biomagnetic activity in
      ovarian lesions.
AB  - In this study we investigated the biomagnetic activity measured with the
      superconducting quantum interference device (SQUID) in benign and malignant
      ovarian lesions using non-linear analysis. We used a single channel
      biomagnetometer SQUID in order to measure the magnetic field emitted from benign
      and malignant ovarian lesions. We can differentiate such biomagnetic activities
      using non-linear analysis. Using the application of non-linear analysis in the
      ovarian lesions together with the use of dimensional calculations we have
      observed a clear saturation value for the dimension of malignant ovarian lesions
      and non-saturation for benign ovarian lesions. The biomagnetic measurements with
      the SQUID and the application of non-linear analysis in benign and malignant
      ovarian lesions, is a promising procedure in assessing and differentiating
      ovarian tumours.

PMID- 15512297
TI  - Urinary leakage during coitus in women.
AB  - During a 4-year period from 1993 to 1997, a total of 2153 women were referred to
      our urogynaecology clinic complaining of urinary incontinence. Of these women,
      228 (10.6%) admitted to coital incontinence. Only 22 of these 228 women
      complained of this symptom without direct questioning. Urine loss occurred during
      penetration in 158 women, during orgasm in 45 women and during both in 25 women.
      Comparison of these groups showed few other differences in their presenting
      symptoms, examination findings, urodynamic data or diagnosis. Genuine stress
      incontinence was present in 79.8% of women with urinary leakage during
      penetration, in 93.2% with leak on orgasm and in 92.0% who leaked on both.
      Detrusor instability was uncommon. In most women who complain of urinary leakage
      during sexual intercourse, the underlying pathophysiological mechanism is
      urethral sphincter incompetence. Compared with women presenting with urinary
      incontinence in the absence of coital incontinence, women with coital leakage had
      a higher incidence of stress and urge incontinence, and a significantly greater
      incidence of anterior vaginal wall prolapse and demonstrable stress incontinence
      on examination.

PMID- 15512298
TI  - Burch colposuspension for the treatment of coital urinary leakage secondary to
      genuine stress incontinence.
AB  - The efficacy of Burch colposuspension in treating the symptom of coital urinary
      leakage in women with genuine stress incontinence has to date never been
      reported. Women who presented to our clinic with regular coital urinary leakage
      and urodynamically proven genuine stress incontinence between 1993 and 1997, and
      who proceeded to a Burch colposuspension procedure, were reviewed to determine
      the outcome of surgery. Fifty-five women were identified (mean age 46.1 years)
      with a mean follow-up interval after surgery of 18 months (range 3-42 months).
      All 55 women had symptoms of stress, urge and coital incontinence preoperatively.
      Following colposuspension, the subjective cure rates for stress and urge
      incontinence were 84% and 85%, respectively. Of 52 women that were sexually
      active after surgery, 81% described no further coital incontinence. The success
      or failure of surgery was not influenced by whether leakage occurred with
      penetration or orgasm preoperatively.

PMID- 15512299
TI  - Jakoscope-an alternative method for minimal access surgery. Early experience in
      hysterectomies.
AB  - Minimal access surgery is now a required technique in gynaecology. This paper
      reports on the first 15 hysterectomies performed through a new in gynaecology
      abdominal wall retractor-the Jakoscope. The abdominal incision was reduced to 4-6
      cm in length. Operation time of 126 minutes (average) is longer than that
      observed in hysterectomies using a conventional incision. With more experience
      with the Jakoscope operation time is lessened associated with less abdominal
      pain, better postoperative recovery, shorter wound healing time and excellent
      cosmetic results. The hospital stay is lessened (from 10 to 3 days) and
      consequently the cost is decreasing.

PMID- 15512300
TI  - Knowledge and attitude to cervical cancer screening among women in Maiduguri,
      Nigeria.
AB  - Five hundred women were studied to determine their knowledge of cervical cancer.
      Less than 10% of the women were aware of the disease or its symptoms. Even fewer
      were aware of cytological screening, the good results obtained in the
      premalignant stage and early invasive stages of the disease. Simple explanation
      showed a good recall at 4-6 weeks. At that time women would accept screening and
      understood its importance. This study shows clearly that education must precede a
      screening programme if it is to succeed.

PMID- 15512301
TI  - Ovarian marsupialisation for polycystic ovarian disease: reality or fiction?

PMID- 15512302
TI  - The pyramidalis muscle.

PMID- 15512303
TI  - Compliance with hormone replacement therapy after prophylactic oophorectomy.

PMID- 15512304
TI  - Cushing's syndrome in pregnancy due to an adrenocorticotropin secreting islet
      cell tumour.

PMID- 15512305
TI  - Pregnancy outcome in a woman with spina bifida and a ventriculo-peritoneal shunt.

PMID- 15512306
TI  - Detailed description of a pregnancy associated with severe chronic fatigue
      syndrome.

PMID- 15512307
TI  - Hereditary elliptocytosis complicating pregnancy.

PMID- 15512308
TI  - Failure to diagnose monoamniotic twin pregnancy by ultrasound but with fortunate
      outcome.

PMID- 15512309
TI  - An unusual case of antepartum haemorrhage.

PMID- 15512310
TI  - Delayed development of laboratory features of HELLP syndrome.

PMID- 15512311
TI  - Optimal fetal outcome despite persistent sinusoidal pattern after external
      cephalic version.

PMID- 15512312
TI  - Spontaneous rupture of a 13 week gravid scarred uterus.

PMID- 15512313
TI  - Twin pregnancy involving complete hydatidiform mole.

PMID- 15512314
TI  - Paget's disease of the vulva with underlying in situ and invasive classical
      lobular breast carcinoma.

PMID- 15512315
TI  - Mucocele of the appendix masquerading as an ovarian mass.

PMID- 15512316
TI  - Caution is required in interpreting high levels of Ca 125 in patients with a
      pelvic mass.

PMID- 15512317
TI  - Medical termination of interstitial ectopic pregnancy using methotrexate and
      mifipristone.

PMID- 15512318
TI  - Primary choriocarcinoma of the ovary with coexisting dysgerminoma of the
      contralateral ovary.

PMID- 15512319
TI  - Transvaginal ovarian cystectomy.

PMID- 15512320
TI  - Tubal ectopic pregnancy-cause of acute abdomen following hysterectomy.

PMID- 15512321
TI  - Septicaemic shock: an unusual presentation of cervical carcinoma.

PMID- 15512322
TI  - Torsion of a hydrosalpinx in an 18-year-old virgin.

PMID- 15512323
TI  - Intestinal obstruction following colposuspension.

PMID- 15512326
TI  - What do maternity statistics tell us about induction of labour?
AB  - The National Maternity Statistics (Department of Health, 1997) show that labour
      is induced in one out of every five pregnancies carried to viability in England.
      Induced labours are associated with higher rates of further intervention such as
      instrumental delivery and caesarean section, and with economic costs resulting
      from longer stay in hospital. Women who are offered induction of labour, whether
      for medical or social reasons, should be advised of the risks of further
      intervention. Information about induction of labour should be given routinely
      during antenatal care since one in five women will have this experience. Care
      providers need to be more aware of the economics of induced labour, a factor
      which has not been taken into account in the longstanding debate on the merits of
      induction of labour for post-term pregnancy.

PMID- 15512327
TI  - The obstetric and neonatal performance of teenage mothers in an Australian
      community.
AB  - A cohort of 7191 single births in Liverpool Hospital, New South Wales was studied
      to examine whether an association between young age and adverse obstetric and
      neonatal outcomes can be supported, and what factors if any could be related to
      poor outcomes. Women were classified into four groups according to their
      confinement age, under the age of 18 years, between 18 and 19 years, between 20
      and 34 years and 35 years or over. Teenage mothers in this community, especially
      under the age of 18 years, were very much disadvantaged in terms of socioeconomic
      status. The overall obstetric performance of teenage mothers was comparable with
      that of adult mothers. The neonatal outcomes were found to be poor in some
      aspects. However, the reasons for the adverse neonatal outcomes among teenagers
      are not due to the young age itself, but other contributing factors, such as
      maternal smoking, parity, and unmarried status.

PMID- 15512328
TI  - Induced abortion and duration of third stage labour in a subsequent pregnancy.
AB  - We set out to evaluate the impact of first trimester induced abortion on the
      duration of third stage labour and related complications in a subsequent
      pregnancy. The study was conducted in Shanghai city at 15 general hospitals (or
      maternity and infant health institutes) from November 1993 to March 1998. We
      identified all nulliparae who came for antenatal care within the first 63 days of
      pregnancy (2953); the women were divided into two cohorts according to their
      previous history of first trimester induced abortion. After enrollment, the women
      were interviewed five times from recruitment until 42 days after delivery. We
      included in the study all 1363 women who had a singleton vaginal live birth. Of
      these women, 703 were primigravida (non-exposed), 534 had had one previous first
      trimester induced abortion, and 126 women had had two or more first trimester
      induced abortions. The duration of third stage labour in minutes was longer in
      women with one or more previous induced abortions (mean=7.32 minutes) compared
      with primigravid women (mean=6.79 minutes). Prolonged third stage labour (>30
      minutes) following one or more induced abortions was seen for 3.4% versus 1.0% in
      primigravid women. After adjusting for a number of potential confounders, women
      with one or more previous first trimester induced abortions had an odds ratio of
      prolonged third stage labour of 2.59 (95%C.I.=1.06-6.37) compared with
      primigravida, especially after an interpregnancy interval of more than 6 months
      (OR=3.24, 95%C.I.=1.29-8.13). The odds ratio of prolonged third stage labour was
      3.14 (95%C.I.=1.22-8.09) if gestational age at the time of the induced abortion
      exceeded 49 days. Women with a first trimester induced abortion had no
      significantly increased risk of postpartum haemorrhage or retained placenta. It
      was concluded that a history of one or more first trimester induced abortions was
      related to an increased risk of prolonged third stage labour in the following
      pregnancy, particularly if the induced abortion was performed after 49 days of
      gestation.

PMID- 15512329
TI  - Retained placenta: a cause of reproductive morbidity in Nigeria.
AB  - This study analysed the reproductive morbidity associated with 91 cases of
      retained placenta at the Obafemi Awolowo University Hospital in Nigeria. The
      incidence of retained placenta in the hospital was 1.4% of all deliveries. Over
      42% of the patients were admitted in haemorrhagic shock; 56.5% were anaemic,
      10.6% severely; 17% had puerperal sepsis while 67% of the women received blood
      transfusions. There was one maternal death (1%). Unbooked patients (74%)
      constituted the largest proportion of cases while inappropriate management of the
      third stage of labour featured in many of the patients. Retained placenta was
      treated with manual removal in 90% of cases. Properly supervised delivery is an
      important component in efforts to reduce the incidence of morbidity associated
      with retained placenta in Nigeria.

PMID- 15512330
TI  - Murphy's Law and the pregnant medical doctor: is pregnancy outcome worse?
AB  - The 'Murphy's Law' concept that doctors have a higher incidence of adverse
      pregnancy outcome is often quoted anecdotally but has never been scientifically
      tested. A group of medical doctors (n =52) were prospectively matched closely
      with a group of non-doctors (n =52) and pregnancy outcome was recorded. There
      were no differences noted in pregnancy outcome between the two groups. Whilst a
      much larger number of doctors is probably required to show a statistically
      significant difference, this first small study shows no clinically relevant
      difference between the two groups. The perception of Murphy's Law and the
      pregnant medical doctor would appear to be a myth.

PMID- 15512331
TI  - Appendectomy in pregnancy: the experience of a university hospital.
AB  - The files of pregnant patients who underwent appendectomy at our hospital over
      the period 1977-96 were studied retrospectively. Forty-six patients were operated
      upon amongst 52 108 deliveries over this period. Of those 27 had uncomplicated
      acute appendicitis and six had one of the complications of acute appendicitis (a
      prevalence of 0.063%). Thirteen had normal appendices (71.7% accuracy). Obstetric
      complications occurred in four patients, with three fetal losses (6.5%). Those
      with complicated appendicitis had significantly delayed presentation, in-hospital
      delay and prolonged postoperative stay. Recently we used diagnostic laparoscopy
      in two patients for diagnosis and to perform appendectomy in one. In conclusion,
      the incidence of acute appendicitis in pregnancy seems to be the same over the
      period of gestation and the diagnostic accuracy seems to be related both to the
      late presentation by the patient and to physician delay. Maternal morbidity and
      fetal loss are mostly limited to those with complicated appendicitis.

PMID- 15512332
TI  - The chaos theory for differentiating fetal biomagnetic brain activity in normal
      and pre-eclamptic pregnancies.
AB  - In this study we investigated the fetal biomagnetic brain activity obtained in
      normal and pre-eclamptic pregnancies using a non-linear analysis. Measurements
      were performed using a single channel biomagnetometer superconducting quantum
      interference device (SQUID) in an electrically shielded room of low magnetic
      noise. Using the application of non-linear analysis and dimensionality
      calculations we have observed a clear saturation for the dimension of the fetal
      biomagnetic brain activity from pre-eclamptic pregnancies and no saturation for
      fetal brain activity in normal pregnancies. Thus, the biomagnetic measurements
      with the SQUID and the application of non-linear analysis, is a promising
      procedure in assessing and differentiating fetal biomagnetic brain activity in
      normal and pre-eclamptic pregnancies.

PMID- 15512333
TI  - Immediate and delayed complications of epidural analgesia in labour and delivery.
AB  - A prospective controlled, longitudinal study investigated the immediate and
      delayed complications of epidural analgesia in labour. One hundred and twenty-two
      parturients were studied: 81 had epidurals in labour and 41 had other forms of
      analgesia. Each parturient was studied over a period of 6 weeks. Epidural
      analgesia in labour and delivery is generally safe. Although the epidural group
      recorded more complications, they tended to be minor ones such as backache,
      headaches, shoulder and neck pain. Epidural blocks have an added advantage of
      being helpful in complicated labours like breech presentations, multiple
      pregnancies, pre-eclampsia, in situations where caesarean section is anticipated
      and in manual removal of the placenta.

PMID- 15512334
TI  - Second trimester maternal serum biochemical screening for Down's syndrome:
      experience of a single obstetric unit.
AB  - The objective of this study was to assess the effects of mid-trimester
      biochemical screening on the prenatal diagnosis of Down's syndrome. All patients
      booked for antenatal care at the Royal Free Hospital are offered a double marker
      biochemical screening test (alpha-fetoprotein and free beta human chorionic
      gonadotrophin). The results of double marker screening tests and the notes of all
      cases of trisomy 21 from 1 April 1993 to 31 March 1995 were reviewed. Of the 6170
      women booked in the antenatal clinic during this 2-year period 4427 (71.8%) took
      up the offer of biochemical screening. Four hundred and twenty-nine (9.7% of
      those screened) were reported positive and 293 karyotypes were performed in this
      group (68.3% uptake) and 253 karyotypes were also performed for other
      indications. Thirteen of 21 affected pregnancies had biochemical screening. The
      detection rate of biochemical screening in women aged <37 years was 0% (0/2) with
      a 8.4% false positive rate. In women aged 37 years the detection rate was 100%
      (11/11) with a false positive rate of 23%. The overall detection rate for Down's
      syndrome was 84.6% and the false positive rate was 9.5%. In conclusion,
      biochemical screening successfully targeted affected pregnancies in women aged 37
      years and was useful in reducing the fetal karyotyping rate. However, it was
      disappointing in the prenatal diagnosis of trisomy 21 in women <37 years old.

PMID- 15512335
TI  - The outcome of pregnancy associated with amphetamine use.
AB  - Thirty cases of pregnancy associated with maternal amphetamine use were studied
      retrospectively fifteen out of the 30 women used amphetamines alone and the other
      15 used other drugs in addition to amphetamines. Women who simultaneously used
      opiates were excluded from this analysis. Women were cared for in a
      multidisciplinary setting and all delivered in one hospital. With support all
      women were encouraged to discontinue drug use. There were 2 perinatal deaths, 1
      from each group (amphetamines alone or amphetamines plus others). The mean birth
      weight were 2878 and 2959 grams respectively and gestational age 38.23 and 37.47
      weeks respectively. If the whole group was divided into women who ceased
      amphetamine use and continued use in pregnancy, there was no marked difference
      between outcome in these 2 subgroups, however, the 2 perinatal deaths both
      occurred in women who continued amphetamine use. The risk of prematurity was
      28.6% and low birth weight 25%, rates which were not reduced by an alteration in
      drug use.

PMID- 15512336
TI  - The effect of maternal exercise on fetal heart rate.
AB  - One hundred and ninety-three women with uncomplicated pregnancies and 44 with
      high-risk pregnancies participated in a 5-minute exercise stress test on a
      bicycle ergometer. All women were in the third trimester of pregnancy.
      Measurements of fetal heart rate were made at intervals of 2, 4, 6, 8, 10, 12,
      16, 20, 25 and 30 minutes. Fetal heart rate was then compared in terms of
      maternal age, parity, consumption of cigarettes, exercise intensity, history of
      activity, cardiotocography score, maternal heart rate at rest, maternal heart
      rate after exercise, fetal sex and birth weight. In low-risk pregnancies an
      increase in fetal heart rate from 143 (124-171) beats per minute (bpm) to 148
      (116-191) bpm was noted after exercise while, in the high-risk pregnancy group, a
      transient decrease from 148 (115-170) bpm to 141 (70-180) bpm was observed. There
      were also 10 cases of significant bradycardia in the high-risk pregnancy group.
      We conclude that the effect of maternal exercise on fetal heart rate is dependent
      on many variables. A fetal bradycardia following exercise is more likely to occur
      in high-risk pregnancies. The use of fetal heart rate variation with exercise
      could be a useful prognostic factor in pregnancy.

PMID- 15512337
TI  - Umbilical artery flow velocity waveforms following maternal exercise.
AB  - The effect of acute exercise on pregnant women in the last trimester of pregnancy
      and the changes in fetal umbilical artery flow velocity waveforms were studied.
      One hundred and forty-three healthy pregnant women underwent an acute exercise
      test. The exercise was performed on an upright bicycle ergometer for 5 minutes,
      followed by 30 minutes of recovery. The baseline control values of umbilical
      artery velocity waveforms were compared with those after exercise. The mean
      exercise intensity achieved was 67.4% (55-90%) of submaximal exercise. Maternal
      heart rate rose significantly from a mean of 89 (68-120) beats per minute at rest
      to a mean of 144 (116-200) beats per minute after exercise (P<0.001). Maternal
      blood pressure rose significantly after exercise from a mean systolic of 112 (80
      150) mmHg to a mean of 147 (120-200) mmHg (P<0.001), and from a mean diastolic of
      67 (40-85) mmHg to a mean of 84 (70-100) mm Hg (P<0.001). The mean fetal
      umbilical pulsatility index (PI) was shown to decrease significantly following
      exercise at 2 and 4 minutes of recovery. It is concluded that (1) an acute
      exercise test of this intensity causes a significant decrease in PI index after 2
      and 4 minutes of recovery; (2) an exercise intensity between 55 and 75% causes a
      decrease in the PI after exercise while exercise of 76-90% of submaximal exercise
      causes a rebound increase after an initial decrease at 2 minutes; (3) it may be
      possible to use this pattern of exercise as an exercise test to differentiate
      between low- and high-risk pregnancies. Studies on high-risk pregnancies are
      being prepared for publication.

PMID- 15512339
TI  - Is cotton-based toilet tissue less irritant to the healing perineum than paper
      products?

PMID- 15512338
TI  - Fetal magnetocardiogram recordings and Fourier spectral analysis.
AB  - Power spectral analysis of fetal magnetocardiogram (FMCG) data was evaluated in
      64 pregnancies, using the non-invasive one channel superconducting quantum
      interference device (DC-SQUID), in order to investigate the power spectral
      amplitude distribution in the frequency range between 2 and 3 Hz. In all cases
      with normal and uncomplicated pregnancies, the data from the fetal heart and
      specifically the QRS complexes, were identifiable and unaffected by any maternal
      cardiac activity and furthermore the power spectral amplitudes, which varied
      between 120 and 350 fT/Hz, were directly related to gestational age.

PMID- 15512340
TI  - The value of leucocyte stix results in predicting bacteriuria and urinary tract
      infection after gynaecological surgery.
AB  - This prospective study was carried out on 454 women to determine the value of a
      leucocyte dipstick test in predicting significant bacteriuria and symptomatic
      postoperative urinary tract infection after routine gynaecological surgery. Urine
      was cultured and tested for leucocytes with a dipstick test (Nephur test,
      Boehringer) at catheter removal and 2 days later. Among the 454 patients, 16.3%
      developed urinary tract infection and 53.3% had significant bacteriuria at least
      once. Among 898 urine specimens, taken from asymptomatic patients, 41.6% were
      stix-positive and 58.4% stix-negative. The predictive value of a positive stix
      result was 59.6% for a positive culture and 27.5% for urinary tract infection. It
      is concluded that, the predictive value of a positive stix for postoperative
      significant bacteriuria or urinary tract infection is too low to be of practical
      use. However, the predictive value of a negative test was high, and few patients
      developed symptomatic urinary tract infection when the leucostix was negative.

PMID- 15512341
TI  - Genetic aetiology of reproductive failures.
AB  - The percentage of couples who have problems with reproduction is growing in
      industrialised nations. Clear genetic aetiology of reproductive failures can be
      discovered in at least one-sixth of them. All these couples should undergo a
      comprehensive genetic examination including karyotyping of both partners. Results
      were obtained over a period of 12 years (1985-97) when studying couples with
      reproductive failures by taking their detailed family histories and by
      cytogenetic analysis of their karyotypes. The study subjects were 410 couples
      (i.e. 820 persons) with different types of reproductive failure from Prague and
      its surroundings. In 3.16%, one member had an aberration of autosomes and, in
      4.38%, one member had an aberration of sex chromosomes. Of these 7.3% had,
      besides infertility and/or repeated spontaneous abortions, the birth of a child
      with a polygenic congenital malformation. A detailed genetic investigation of
      couples with reproductive failures should not be neglected when trying to find
      the best treatment.

PMID- 15512342
TI  - Human immunodeficiency virus antibody in patients with cancer of the uterine
      cervix undergoing radiotherapy: clinical stages, histological grade and outcome
      of radiotherapy.
AB  - One hundred and twenty consecutive patients with cancer of the uterine cervix
      were screened for human immunodeficiency virus (HIV) seropositivity before and
      after radiotherapy. The severity of the disease in terms of clinical staging and
      histological grading of HIV seropositive women was compared with that of
      seronegative women. The result showed a prevalence rate of 4.2% for HIV
      seropositivity which was similar to the rate quoted for the general populace in
      Nigeria. The HIV seropositive women presented with more severe disease state than
      the HIV seronegative women. The mean duration of remission was significantly
      shorter in the HIV seropositive women following radiotherapy (18.36+/3.96 vs.
      24.24+/-6.3 months). It was concluded that HIV infection increases the severity
      and progression of cancer of the cervix in Nigerians. Radiotherapy has no effect
      on the patients' seropositivity and possibly no effect on the virus. A more
      aggressive treatment of carcinoma of the cervix and closer follow-up of HIV
      seropositive patients following treatment are necessary.

PMID- 15512343
TI  - Genital tract infections and the specialist gynaecologist: a survey of
      perception, diagnosis and treatment.
AB  - The study was designed to investigate the attitude of gynaecologists to the
      management of genital tract infections in the North West Region of England. A
      postal questionnaire was sent to all members and fellows of The Royal College of
      Obstetricians and Gynaecologists with addresses in the region. A response rate of
      71% was achieved. Of these 67% were male and more than 97% had been in the
      speciality for more than 5 years. Only 90.5% routinely obtain swabs from the
      posterior fornix; none from the pharynx. Forty-two per cent thought there might
      be a role for the genitourinary physician in the management of genital tract
      infections. Nineteen per cent engaged in consort tracing and only 22.6% carried
      out tests of cure before discharging the patients. Fifty-one per cent thought
      there could be grounds for litigation for not carrying out contact tracing and
      27.4% agreed that not doing tests of cure may be regarded as negligence. This
      study revealed that there is a need for adequate training of gynaecologists with
      regards to the facilities available within the National Health Service.

PMID- 15512344
TI  - Is involvement of the surgical margins of large loop excision of the cervical
      transformation zone specimens for cervical intraepithelial neoplasia III a risk
      factor for persistent cervical intraepithelial neoplasia?
AB  - We aimed to test the hypothesis that patients with cervical intraepithelial
      neoplasia (CIN) III treated by large loop excision of the cervical transformation
      zone (LLETZ) are more likely to suffer recurrence of cervical abnormalities if
      the CIN reaches the margins of the index specimen. Three hundred and forty-five
      women treated by LLETZ in 1991, and 1992, and in whom the histological diagnosis
      was CIN III, were studied. The reports were reviewed and the cases were
      categorised as completely excised, incompletely excised, or undetermined.
      Cytological follow-up, or in some cases histological follow-up in the same year
      and in each of the 5 following years was tabulated. Follow-up data were recorded
      from the same and also surrounding institutions. The chi-squared test was used to
      compare the differences in recurrence rates between the three groups at the
      various points in time. A small advantage was demonstrated for those cases where
      excision was complete. This was statistically significant in the third following
      year (P=0.022). The resection margin status of LLETZ specimens for CIN III has
      only a minor effect on the likelihood of recurrence. Nevertheless, recording the
      status may be important in case of unexpected invasion. The relative reassurance
      the information will provide when the lesion has been excised may also be seen as
      worthwhile.

PMID- 15512345
TI  - Sexual attitudes and their relation to cervical intraepithelial neoplasia in
      Maiduguri, Nigeria.
AB  - Five hundred randomly selected sexually active women attending antenatal,
      postnatal, family planning and gynaecological clinics in the Department of
      Obstetrics and Gynaecology, University of Maiduguri Teaching Hospital, had
      questionnaires administered on their sexual attitudes/ behaviour and their
      'pap'smears taken for cytological assessment. The aim was to identify any
      significant association between sexual attitudes/behaviour and cervical
      intraepithelial neoplasia (CIN) for the purpose of targeting the population most
      at risk. Ninety-one women had varying degrees of CIN, a prevalence rate of 18.2%.
      However, multiple sexual partners was the only factor incriminated to
      significantly increase the risk of occurrence of CIN. Targeting women with
      multiple sexual partners may help in directing limited screening resources to
      those more likely to be positive.

PMID- 15512346
TI  - The role of GnRH analogue therapy in the management of proximal fallopian tube
      occlusion.
AB  - Ten infertile women were diagnosed as having bilateral or unilateral proximal
      tubal occlusion in the presence of minimal to mild endometriosis. They were
      treated with GnRH analogue for 3 months. The aim was to assess the usefulness of
      therapy in reversing the tubal block. Diagnosis was based on
      hysterosalpingography, laparoscopy and hysteroscopy. At completion of therapy
      tubal patency was confirmed by hysterosalpingography. Three patients had
      bilateral cornual block whereas seven had unilateral. All patients had achieved
      bilateral tubal patency immediately following therapy. Four women achieved
      pregnancy during a follow-up of 3-20 months. Our results show that if early
      endometriosis causes proximal tubal occlusion (without fibrosis) GnRH analogues
      may be considered as the first line of treatment.

PMID- 15512347
TI  - Infarction of a placental chorioangioma mimicking placental abruption.

PMID- 15512348
TI  - A duplication of the descending colon presenting in pregnancy.

PMID- 15512349
TI  - Maternal survival following an unusual suicide attempt in pregnancy.

PMID- 15512350
TI  - Laryngeal atresia-a cause of hydrops fetalis.

PMID- 15512351
TI  - Prolonged fetal tachycardia-an unusual complication of external cephalic version.

PMID- 15512352
TI  - Tuberous sclerosis in a Chinese baby presented with a pleural effusion and
      cardiac tumour during prenatal period.

PMID- 15512353
TI  - A successful pregnancy in a transport in vitro fertilisation case using randomly
      selected testicular immotile sperm and intracytoplasmic sperm injection.

PMID- 15512354
TI  - Conservative surgical management of an intramyometrial ectopic pregnancy.

PMID- 15512355
TI  - Menorrhagia due to endometrial stromal sarcoma.

PMID- 15512356
TI  - Sporadic Perrault syndrome.

PMID- 15512357
TI  - Combined laparoscopic and hysteroscopic guided removal of an interstitial
      pregnancy.

PMID- 15512358
TI  - Pedunculated uterine leiomyoma causing acute urinary stress incontinence.

PMID- 15512359
TI  - Vulvar cancer in pregnancy.

PMID- 15512361
TI  - FIGO Committee for the Ethical Aspects of Human Reproduction and Women's Health
      Committee Statement on Ethical Guidelines (Cairo, March 1998).

PMID- 15512363
TI  - The value of phytoestrogens as a possible therapeutic option in postmenopausal
      women with coronary heart disease.
AB  - Large epidemiological studies have proved that the risk of coronary heart disease
      in postmenopausal women can be decreased by oestrogen replacement therapy. The
      effect is triggered by metabolic processes in the liver (decrease of LDL
      cholesterol, increase of HDL-cholesterol) as well as by direct impact on the
      arterial wall (anti-oxidation, relaxation, anti-proliferation). The therapeutical
      usage of oestrogens is limited by an increased incidence of breast and
      endometrial cancer. Cyclic application of progestogens virtually eliminates the
      risk. Unfortunately, progestogens may antagonise the atheroprotective effect of
      oestrogens. Structurally modified oestrogens as well as selective oestrogen
      receptor modulators were investigated in clinical trials. They might provide the
      desired atheroprotective effects of oestrogen without negative side effects on
      the mammary gland or the endometrium. In this respect isoflavones also known as
      phytoestrogens, were analysed. They are widespread and occur naturally in many
      plants, especially in soy products. Cell culture and animal experiments as well
      as clinical studies revealed that phytoestrogens such as genistein and daidzein
      act atheroprotectively in the same way as oestrogen. Effects on the mammary gland
      or the endometrium could not be detected, but positive side effects on the bone
      metabolism and the decrease of certain types of cancer could be observed. In
      total, the therapeutical application of phytoestrogens in postmenopausal women
      seems to be of real and great benefit. We conclude that in women the risk of
      death from coronary heart disease increases after the onset of menopause.
      Recently discovered properties of phyto-oestrogens seem to be of great benefit as
      they do not seem to have any side effects on the mammary gland and the
      endometrium which are limiting factors for oestrogen replacement therapy.

PMID- 15512364
TI  - Failed instrumental delivery: how safe is the use of a second instrument?
AB  - An audit of failed instrumental deliveries was undertaken to assess the incidence
      of complications and the adequacy of documentation. When one instrument has
      failed to effect delivery, the use of a second instrument could in most cases be
      used to complete the delivery without harm to the mother or baby. However in a
      small but significant number of cases there are severe maternal or perinatal
      complications, and these could be the subject of litigation. This could be
      avoided by adequate pre-application assessment, standard conduct of instrumental
      delivery and full documentation. Inadequate documentation could be overcome by
      the use of a pro forma. Selective use of plastic and metal cups could reduce the
      incidence of failed attempts.

PMID- 15512365
TI  - Has pelvimetry a role in current obstetric practice?
AB  - Radiological pelvimetry is still requested in some centres before planned vaginal
      delivery for breech presentation or following a previous caesarean section. In a
      retrospective review of the utilisation of pelvimetry in 167 cases in our
      department, 103 (62%) and 64 (38%) had pelvimetry in the postnatal and antenatal
      periods respectively. Antero-posterior inlet and outlet diameters were inadequate
      in 19.2% and 16.2% respectively. Of those who had postnatal pelvimetry, only 36
      (35%) returned to our unit for further confinement and the caesarean section rate
      in this group was 75%. The main indications for antenatal pelvimetry were breech
      presentation (28), previous caesarean section (23) and anticipated cephalopelvic
      disproportion (13). The caesarean section rates in these groups were 82%, 70% and
      45% respectively. However, the emergency caesarean section rate in the breech
      presentation group was 28%. Nine patients (32%) of those who had breech
      presentation and delivered by elective caesarean section had normal pelvic
      measurements. Pelvimetry should only be performed if its results will influence
      the mode of delivery. Pelvimetry may be useful in selecting fetuses with breech
      presentation for vaginal delivery or elective caesarean section. However it would
      increase the likelihood of caesarean section in cephalic presentation.

PMID- 15512366
TI  - Does sexual intercourse at term influence the onset of labour? A survey of
      attitudes of patients and their partners.
AB  - It is not known if sexual intercourse at term influences the onset of labour, but
      there are several theoretical reasons why it may. Performing a definitive study
      to address this issue would pose practical and ethical difficulties. This study
      therefore sought to assess whether the scientific answer to this issue is of
      importance to pregnant women and their partners. Women and their partners
      attending antenatal clinics were asked to complete a questionnaire. Eighty-six
      per cent of women and 93% of men questioned wished to know if sexual intercourse
      did influence the onset of labour. If sexual intercourse did influence the onset
      of labour then a large proportion of those questioned indicated that it would
      have an effect on sexual activity at term. This study indicates that well
      designed studies should be performed to assess whether sexual intercourse at term
      is implicated in the onset of labour.

PMID- 15512367
TI  - The effect of maternal exercise on umbilical artery velocimetry waveforms in
      intrauterine growth retardation.
AB  - Eighteen pregnant women affected with fetal growth retardation in the last
      trimester were exercised. The mean maternal heart rate increased significantly
      from 140 beats per minute (bpm) (120-188 bpm) at rest to 172 bpm (163- 178 bpm)
      after exercise. The mean exercise intensity was 65% (56-85%) of submaximal
      exercise. Maternal systolic blood pressure rose significantly from a mean of 116
      mmHg (100-140 mmHg) to 159 mmHg (120-190 mmHg) and the diastolic blood pressure
      rose significantly from a mean of 72 mmHg (55-110 mmHg) to 90 mmHg (80-110 mmHg).
      The umbilical artery pulsatility index (PI), after an initial decrease, showed a
      12% rise at 8, 16 and 30 minutes of recovery. Patients who smoked had a
      significantly higher umbilical artery PI before and after exercise. Less active
      Patients had a higher PI before and after exercise than active ones. Infants
      weighing 1.9-2.5 kg at birth had a higher PI than those weighing 2.6-3.3 kg. Male
      fetuses had a significantly higher PI than female fetuses.

PMID- 15512368
TI  - Obstetric hazards of maternal obesity.
AB  - To test the hypothesis that obesity represents a risk factor in pregnancy, we
      conducted a prospective case-control study to determine whether or not there was
      any divergence in the obstetric outcome among 132 obese women from that in a
      control group of 136 non-obese patients. Obese mothers had an increased incidence
      of pregnancy-induced hypertension and gestational diabetes but there was no
      significant difference in the duration of pregnancy or in the frequency of low
      Apgar score at 1 minute. The favourable fetal outcome in obese parturients
      reflects an increased awareness of the possible medical and obstetric
      complications and an early recourse to abdominal delivery.

PMID- 15512369
TI  - Colorectal cancer associated with pregnancy in Kaduna.
AB  - The incidence of colorectal cancer associated with pregnancy is low. Only 2-6% of
      all females suffering from colorectal cancer are within the child bearing age
      (i.e. under 40 years). This paper describes the experience at the Ahmadu Belle
      University Teaching Hospital, Kaduna, Nigeria, from 1 January 1975 to 31 December
      1997. Twenty-five cases of colorectal cancer associated with pregnancy were seen
      and treated; 15 cases in which colorectal cancer occurred de novo in pregnant
      patients; and 10 cases in which pregnancy(ies) occurred in patients with a
      previous diagnosis of colorectal cancer. Treatment of the cancer, future
      pregnancies and their management, and the question of possible prophylactic
      oophorectomy in selected patients are discussed.

PMID- 15512370
TI  - Application of artificial neural networks for detection of abnormal fetal heart
      rate pattern: a comparison with conventional algorithms.
AB  - Cardiotocography signals were sampled during labour in 53 patients. A recurrent
      artificial neural network with hidden layer feedback was trained and performance
      was compared with that of several conventional systems. Correct and false
      positive rates of all systems tested were calculated. To ensure that the
      performance of neural networks was not just caused by using different cut-off
      levels, the threshold used for conventional methods were also adapted and
      optimised. The correct positives rate of neural networks was between 0.72 and
      0.9, and the false positive rate between 0.2 and 0.4. Before optimising,
      conventional algorithms produced a very low correct positive (0.02-0.5) and a low
      false positive rate (0.0-0.08). After adjusting the parameters, the tested neural
      networks still performed better than optimised conventional systems.

PMID- 15512371
TI  - Obstetrics and perinatal outcome of pregnancies after the age of 45.
AB  - We set out to describe the maternal and perinatal outcome of pregnancies in women
      >/= 45 years old at the time of delivery. A retrospective review of hospital
      deliveries after 28 weeks of pregnancy was performed at the Princess Badeea
      Teaching Hospital (PBTH) in North Jordan for patients delivered between 1 April
      1994 and 31 December 1997. During the study period, there were 114 women aged >/=
      45 years at delivery at the PBTH. The incidence was 3.3 per 1000 births. The
      median maternal age was 45 years. The majority of women (81.6%) were 45-46 years
      old. Maternal ages were 45 (n =64), 46 (n =29), 47 (n =9), 48 (n =8), 49 (n =2)
      and 50 (n =2) years. Median gravidity was 10, median parity was seven. Forty-four
      (38.6%) patients had obstetric complications. The most frequent complication was
      diabetes mellitus (9.6%), followed by hypertension (4.4%). Caesarean section was
      performed in 32.5%. There were nine stillbirths and four early neonatal deaths,
      the perinatal mortality rate was 114/1000 births. We conclude that women >/= 45
      years old at delivery have high perinatal mortality rate and we also noted a
      higher incidence of placental abruption, placenta praevia and caesarean delivery,
      compared with a younger group of women.

PMID- 15512372
TI  - Fecundity in the modern city: a comparison of couples attending antenatal clinics
      in Manchester (UK) and Melbourne (Australia).
AB  - To determine the characteristics of couples with resolved subfecundity and to
      compare these findings in two geographically distant centres, a self-reporting
      questionnaire was completed by a sample of women attending six antenatal clinics
      in Greater Manchester, UK and five antenatal clinics in Melbourne, Australia. A
      total of 2158 pregnant women, 1106 from Manchester and 1052 from Melbourne
      participated in the study. The prevalence of subfecundity (proportion of women
      who failed to conceive current pregnancy within 12 months of unprotected
      intercourse) and demographic and medical factors potentially related to
      subfecundity were measured. The samples from the two cities had similar medical
      characteristics, but several socioeconomic and cultural differences were
      detected. Characteristics which independently correlated with decreased fecundity
      were increasing parental age, previous pregnancy, previous miscarriage, maternal
      smoking before conception and low socioeconomic status. Increased body mass index
      was also a significant, independent predictor of decreased fecundity, but in the
      Melbourne sample only. Subfecundity was found to be influenced by a combination
      of parental and socioeconomic factors as well as previous pregnancy. The factors
      identified were similar in two modern industrial societies in very different
      geographical locations, only their relative importance differing between
      Australia and the UK.

PMID- 15512373
TI  - Microwave endometrial ablation for menorrhagia.
AB  - Sixteen women requesting surgical treatment of menorrhagia were recruited for a
      study on microwave endometrial ablation. The mean age at treatment was 41.4 years
      and all patients had completed their family and were pre-menopausal. Average
      treatment time was 2 minutes 6 seconds. All patients reported a reduction in
      their menstrual loss and 87.5% were satisfied with their treatment after 1 year
      follow-up. One patient required overnight admission for analgesia while 15
      patients were treated on a day case basis using light general anaesthesia. Sixty
      seven per cent of patients reported a reduction in dysmenorrhoea scores at 1
      year, two patients reported no change in symptoms and one patient reported a
      modest increase. One patient had a hysterectomy 10 months after treatment despite
      being amenorrhoeic. The indication for hysterectomy was pelvic pain (which was
      present before endometrial ablation). There were few minor complications but no
      uterine perforation or emergency hysterectomies.

PMID- 15512375
TI  - A 5-year follow up of mildly dyskaryotic smears, comparing colposcopy with
      expectant management.
AB  - The purpose of this study was to see if the National Health Service Cervical
      Screening Programme's guidelines were appropriate when they recommended that
      mildly dyskaryotic smears were repeated before referral for colposcopy. We
      identified all those with a mildly dyskaryotic smear, and followed them over 5
      years, to compare those that had colposcopy and those that did not. In total, 269
      women were followed and 35% of these only had the one mild smear. Of those whose
      smear returned to normal after the initial mild smear, 84% remained normal over
      the 5-year period. Of those whose smear did not return to normal, i.e. those that
      required a colposcopy, 74% returned to normal after the colposcopy.

PMID- 15512374
TI  - Should women with genital condyloma acuminata have routine diagnostic colposcopy
      in addition to cervical smear screening?
AB  - We aimed to evaluate the difference in the pick up rate of high grade cervical
      abnormalities using both primary colposcopy and cervical smear compared with
      cervical cytology screen only on women with genital warts. We also wished to
      establish whether this group was at high risk of sexually transmittable
      infections (STIs) and whether there is a correlation between those with high
      grade CIN and other STIs. This was a retrospective analysis based in the
      Department of Genito-Urinary Medicine, Dundee Teaching Hospitals Trust, Dundee,
      UK. We studied all women (n =117) attending the Department with genital warts
      between January 1995 and March 1997 who were screened by both cervical cytology
      and colposcopy High grade cervical abnormalities (CIN II-CIN III) were diagnosed
      in 10 patients (8.5.%) using cervical screening only and in 41 patients (35%)
      (CIN II-III) when primary colposcopy and histopathology were undertaken. Of 117
      women screened for sexual transmittable infection there were 53 with a positive
      diagnosis (48%). Of the 53 positive there were 17 women (30%) with high grade
      CIN. We conclude that women with genital warts are a high risk group, both in
      terms of having high grade cervical abnormalities and sexually transmittable
      infection. The result suggests that, when practicable primary colposcopy should
      be performed as a routine screening tool, on this group of patients over and
      above cervical cytology screening. All patients with genital warts should be
      referred to genitourinary medicine for STI screening.

PMID- 15512376
TI  - A prospective study of asymptomatic Chlamydia trachomatis in Barbadian women.
AB  - A prospective study to determine the prevalence of asymptomatic female genital
      tract Chlamydia trachomatis infection was performed on 167 women at the Queen
      Elizabeth Hospital, Barbados, West Indies and at a private clinic. The ELISA
      (Microtrak, chlamydia EIA, Syva, CA) method was used to detect Chlamydia
      trachomatis antigen. Nineteen (11.4% 95% CI 6.5-16.3) women were found positive.
      The efficacy of a single 1 gram dose of azithromycin given orally to 18 patients
      was tested after 4 weeks. One patient who was pregnant was given 500 mg
      erythromycin four times daily orally for 1 week. Only six patients (including the
      pregnant patient) reported for follow up. All six repeat swabs were negative for
      C. trachomatis antigen. The prevalence of 11.4% asymptomatic chlamydial infection
      in endocervical swabs in Barbadian women is in agreement with a previous study
      which reported a prevalence of 18.4% +/7.8%. Patient compliance was assured,
      using a single dose of azithromycin. It was found to be as effective as
      doxycyline and ciprofloxacin as reported by other workers.

PMID- 15512377
TI  - Topical antiseptic agent after large loop excision of the transformation zone:
      results of a randomised controlled trial.
AB  - One hundred patients undergoing large loop excision of the transformation zone
      (LLETZ) were randomised to receive postoperative local treatment with sultrin
      (sulphathiazole 3.42%, sulphacetamide 2.86%, sulphabenzamide 3.7%) pessaries: one
      pessary twice daily for 5 days, or no treatment. Outcome measures included
      duration and severity of vaginal bleeding, discharge, pelvic pain, need for oral
      antibiotic therapy and unplanned hospital admission. There was no significant
      difference in the severity of symptoms in the treatment and control groups for
      bleeding, discharge or pain, averaged over the study period. Postoperative
      morbidity following LLETZ was frequent but mild. Use of prophylactic antiseptic
      agents is not recommended.

PMID- 15512378
TI  - Patient satisfaction in gynaecological outpatient clinic attendances.
AB  - A questionnaire was used to assess patients' perception of and satisfaction with
      gynaecology outpatient appointment date and waiting times at gynaecology
      outpatient clinics. While 95% were satisfied with the overall service, 19%
      expressed dissatisfaction with waiting times for first appointment and 26% with
      the waiting time at the clinic. These findings are discussed in the light of the
      recommendations of the Patient's Charter and with respect to reorganising
      outpatient gynaecology services to improve efficiency.

PMID- 15512379
TI  - The efficiency of hysterosalpingo-contrastsonography (HyCoSy) in the evaluation
      of tubal patency.
AB  - Radiological hysterosalpingography (R-HSG) and laparoscopic hydrotubation are
      widely used for the evaluation of tubal patency in infertile patients. Both
      methods have advantages and disadvantages that limit their use. In this study,
      the efficiency of a new method (HyCoSy) in the diagnosis of tubal patency was
      evaluated by comparing it with the traditional methods (R-HSG and laparoscopic
      hydrotubation). In a total of 47 infertile patients HyCoSy was performed in the
      evaluation of tubal patency, between November 1996 and May 1997 at Akdeniz
      University, Department of Obstetrics and Gynaecology. In 18 of 47 patients, the
      traditional methods were also performed and the results were compared with
      HyCoSy. In this study laparoscopic hydrotubation was accepted as the 'gold
      standard'. In 36 fallopian tubes of 18 patients the clinical concordance of
      HyCoSy and laparoscopic hydrotubation was 86%, R-HSG and laparoscopic
      hydrotubation was 77%. In this study it was shown that in the evaluation of tubal
      patency the new method; HyCoSy is statistically comparable with the traditional
      methods. HyCoSy has the advantage of being easily repeatable compared with R-HSG
      and this may reduce false-positive results. Furthermore HyCoSy is a welltolerated
      and easily applicable method compared with R-HSG.

PMID- 15512380
TI  - The expression of the proliferation marker Ki-67 and oestrogen and progesterone
      receptors in the proximal and distal fallopian tube.
AB  - Significant epithelial proliferation is identified more frequently in the
      fallopian tube in patients with ovarian tumours than in control patients. More
      extensive sampling of the fallopian tube is also associated with a more frequent
      identification of epithelial proliferation. We compared cellular proliferation at
      either end of the fallopian tube as detected with an antiserum to the Ki-67
      protein. Variations in oestrogen and progesterone receptor proteins were also
      examined. Proliferative activity as expressed by the Ki-67 protein, and oestrogen
      receptor expression was greater in the proximal fallopian tube and progesterone
      receptor expression was greater in the distal fallopian tube. Only the difference
      in progesterone receptor expression was statistically significant (P =0.0431).
      This study indicates that variations in Ki-67, oestrogen and progesterone
      receptor protein expression occur at different sites in the fallopian tube. This
      should be taken into account when planning studies of epithelial cell
      proliferation in the fallopian tube in the future.

PMID- 15512381
TI  - The cost of a hysterectomy in a UK hospital.
AB  - Vaginal hysterectomy has been demonstrated to be the cheapest route to perform a
      hysterectomy but no detailed costing has been performed in the United Kingdom. In
      this study the costs incurred by a UK teaching hospital for 30 women aged between
      40 and 50 years of age undergoing either abdominal (AH), laparoscopically
      assisted vaginal hysterectomy (LH) were compared with vaginal hysterectomy (VH).
      VH was significantly the cheapest procedure (993.00 Pounds, 95th Cl 883.20 Pounds
      to 1124.80 Pounds) and there was a tendency for LH (1148.00 Pounds, 95th Cl
      1006.80 Pounds to 1289.20 Pounds) to be less expensive than AH (1340.00 Pounds,
      95th CI 1080.80 Pounds to 1595.20 Pounds); this difference may be reversed if
      disposable laparoscopic instruments were to be used for LH. Our study agrees with
      data from other countries showing that VH is the cheapest type of hysterectomy.
      With the added benefits of shorter hospital stay, convalescence and return to
      work, effort should be directed towards increasing the proportion of
      hysterectomies performed vaginally in the UK.

PMID- 15512382
TI  - Histological types of ovarian tumours as seen in an African teaching hospital in
      north-eastern Nigeria.
AB  - During the period January 1989 to December 1997, there were 116 histological
      proven ovarian neoplasms seen in the University of Maiduguri Teaching Hospital,
      Maiduguri. Ninety-two (79.3%) patients had benign tumours while the remaining
      20.7% had ovarian cancer. Epithelial tumour were the commonest histological type
      (40.7%) followed by germ cell tumours. Benign cystic teratoma (25.0%) was the
      commonest benign tumour while the commonest malignant tumour was serous
      cystadenocarcinoma (7.7%).

PMID- 15512383
TI  - Sudden maternal death in pregnancy complicated by anorexia nervosa.

PMID- 15512384
TI  - Chronic hypokalaemia in pregnancy secondary to hyperemesis gravidarum.

PMID- 15512385
TI  - Grossly elevated placental derived alkaline phosphatase in pregnancy as a marker
      for uteroplacental vascular disease.

PMID- 15512386
TI  - Fetal fibronectin and placental abruption.

PMID- 15512387
TI  - C-1 esterase inhibitor prophylaxis for delivery in hereditary angioedema.

PMID- 15512389
TI  - Familial Mediterranean fever in a pregnant woman.

PMID- 15512388
TI  - Placenta praevia percreta with bladder infiltration.

PMID- 15512390
TI  - Vaginal delivery after abdominal wall replacement by Marlex mesh.

PMID- 15512391
TI  - Hydrostatic replacement of acute inversion of the uterus can cause acute
      pulmonary oedema by intrauterine fluid intravasation.

PMID- 15512392
TI  - Bilateral Mullerian duct remnants. A scanning electron microscope study in a case
      of complete androgen insensitivity syndrome.

PMID- 15512393
TI  - A cervical ectopic pregnancy, diagnosed at 17 weeks' gestation.

PMID- 15512394
TI  - Three steps management of irreducible complete procidentia complicated by vesical
      calculi.

PMID- 15512395
TI  - Endometrial adenocarcinoma: an unusual presentation with acute urinary retention
      secondary to haematocolpos.

PMID- 15512396
TI  - Sarcoma botyroides-an unusual case of a cervical polyp.

PMID- 15512397
TI  - Clear cell adenocarcinoma of the peritoneum associated with clear cell
      adenocarcinoma arising in an endometrial polyp.

PMID- 15512398
TI  - Adenoid cystic carcinoma of Bartholin's gland: two cases.

PMID- 15512399
TI  - Primary ovarian mixed type carcinoid tumour.

PMID- 15512400
TI  - Transvaginal ultrasonography for placenta site.

PMID- 15512402
TI  - Vulval pain syndrome study day, Derby, 5 March 1999.

PMID- 15512404
TI  - Screening for gestational diabetes in the United Kingdom: a national survey.
AB  - To determine the attitudes of British obstetricians to screening for gestational
      diabetes a postal questionnaire survey was undertaken. A questionnaire was sent
      to a single obstetrician in each of 255 obstetric hospitals identified in the
      United Kingdom. Of the 189 (75%) units that replied, only 42.3% had a protocol
      for screening for gestational diabetes. Routine antenatal screening was performed
      by urinalysis and blood glucose tests in 89.4% and 32.8% of units respectively.
      Clinical risk factors were used as an indication for routine blood glucose
      testing in 91.5% units. Following a positive screening test 54.5% of units
      performed a 75 g oral glucose tolerance test (GTT) and of these 64% relied on the
      World Health Organisation diagnostic criteria to interpret the result. There
      currently appears to be widespread variation in the practice of screening for
      gestational diabetes in the United Kingdom.

PMID- 15512405
TI  - Emergency obstetric hysterectomy - an increasing incidence.
AB  - Ten women underwent obstetric hysterectomy at St George's Hospital, London
      between 1992 and 1998, with an apparent seven-fold increase in incidence in
      recent years. All hysterectomies were performed as emergency procedures, with
      massive postpartum haemorrhage being the major indication for operation in nine
      cases. Abnormal placentation was the single commonest cause, seven cases being
      associated with previous caesarean section. There were no maternal or fetal
      mortalities, but major surgical complications, including urinary tract and
      vascular injury occurred in one case. In view of the increasing risk of obstetric
      hysterectomy following previous caesarean section, high risk cases associated
      with abnormal placentation may be identified using ultrasound, allowing
      appropriate pre-operative counselling regarding the risk of peripartum
      hysterectomy.

PMID- 15512406
TI  - Placental praevia and accreta: an analysis of two-years' experience.
AB  - This retrospective review of the case records was designed to determine the
      relationship between previous caesarean section and subsequent development of
      placenta praevia and placenta praevia with accreta. All women delivered with the
      diagnosis of placenta praevia at Princess Badeea Teaching Hospital from 1 January
      1995 to 31 December 1996 were analysed. There were 18 651 deliveries in the study
      period. Sixty-five had placenta praevia, 21 of whom had a history of previous
      caesarean. The incidence of placenta praevia was significantly increased in those
      with a previous caesarean section (1.87%) compared with those with an unscarred
      uterus (0.25%) (P<0.0001). The risk increased as the number of previous caesarean
      sections increased. We also conclude that there is a high association between
      anterior placenta praevia, placenta accreta and previous caesarean section. This
      was enhanced with the increasing number of previous caesarean sections.

PMID- 15512407
TI  - Twin pregnancies: incidence and outcome - Riyadh Armed Forces Hospital
      experience.
AB  - A retrospective study of twin births at the Armed Forces Hospital, Riyadh, from
      January 1987 to December 1996 was carried out. There were 62 739 deliveries and
      598 sets of twins. The incidence of twins was one in 105 maternities. The
      perinatal mortality rate was 46 per 1000 births compared with 12.3 per thousand
      for singletons. Premature delivery (<34 weeks) and very low birth weight infants
      (<1500 g) accounted for 12.5% and 8.7% of the twin deliveries respectively, but
      contributed to 60% and 63.6% of the total deaths respectively. Nineteen (3.2%)
      patients received no antenatal care, however, they contributed to 16.2% of the
      total deaths. This report represents our experience at the Armed Forces Hospital,
      Riyadh, Saudi Arabia on the management of twin pregnancies during a period of 10
      years.

PMID- 15512408
TI  - Marfan syndrome and pregnancy - a district hospital perspective.
AB  - Marfan syndrome is an uncommon condition in pregnancy. Few district hospital
      obstetricians except those who work in areas with Marfan family clusters have
      experience in managing patients with this condition. Modern medical and surgical
      treatments have resulted in improved longevity and quality of life for many with
      this condition. For these reasons, there is an increased likelihood that more
      obstetricians may in the future have to manage a pregnant Marfan patient even
      though their involvement may only be in the early stages of her pregnancy. It is
      important that every district hospital obstetrician is aware of the implications
      of the condition in pregnancy and has a clear idea of the principles of
      management. This paper is based on experience gained from working in a district
      hospital in an area with a cluster of Marfan families and review of the relevant
      medical literature. The main risk is aortic dissection. Aortic root measurements
      and family history help to identify those at greatest risk.

PMID- 15512409
TI  - Prospective study of external cephalic version in Glasgow: patient selection,
      outcome and factors associated with outcome.
AB  - Data were collected prospectively on all 67 women who underwent an attempt at
      external cephalic version (ECV) over 1 year in the four Glasgow maternity
      hospitals. Ultrasonography was used in all women. However, tocolytics were used
      in only two (6%) nulliparous women despite published evidence of their efficacy.
      Only 25 (37%) women undergoing ECV had a free presenting part which is known to
      be associated with success. Seventeen (25%) women were less than 37 weeks
      pregnant despite spontaneous version being common at this stage. ECV was
      successful in only 26 (39%) women and only 18 (27%) had a vaginal cephalic
      delivery. These results compare unfavourably with published results of around two
      thirds for both end-points. Although publication bias is likely, patient
      selection, under-usage of tocolytics and lack of experience may also be factors.
      Consideration should be given to a reduced number of operators who can maximise
      their throughput and expertise.

PMID- 15512410
TI  - Operative vaginal delivery rates in the United Kingdom.
AB  - Operative vaginal delivery with the vacuum extractor or forceps is integral to
      the practice of obstetrics worldwide. The rates at which obstetricians in
      different countries intervene vary enormously. The wide range of operative
      vaginal delivery rates reported in the United Kingdom has been noted as a cause
      for concern. At a Royal College of Obstetricians and Gynaecologists consultants'
      conference, the participants of a discussion group were surveyed regarding their
      'actual' and perceived 'optimal' operative vaginal delivery rate. The 'actual'
      operative vaginal delivery rate was 10.5% and the perceived 'optimal' was 8.7%.
      Given that there are approximately 600 000 births per annum in the UK, if the
      optimal delivery rate was achieved over 10 000 operative vaginal deliveries could
      be avoided, with significant reductions in maternal morbidity. Reductions could
      be achieved by examining practice at a number of points in the care pathway.
      Individual units should examine their practice to establish whether their
      guidelines and continuing education programmes reflect current knowledge of best
      practice.

PMID- 15512411
TI  - Maternal serum screening for Down syndrome in women aged 40 years and over.
AB  - Two hundred and thirty-nine women aged 40 years were booked for delivery at
      Kettering General Hospital from 1992 to 1997. Six women were not eligible for the
      triple test (TT) as they booked too late. Eighty-eight women declined TT. The
      reasons were; fear and anxiety about the risk of miscarriage associated with
      amniocentesis if the test result were a high risk (70.5%), worries about the
      false negative result associated with the TT (20.5%) and reluctance to terminate
      the pregnancies if the fetus were abnormal (9%). One hundred and forty-five women
      (62.2%) elected for TT of whom 91 (62.8%) had received a high risk results. Of
      the women who received a high-risk result 61/91 (67%) had an amniocentesis. The
      study provides an accurate probability of receiving a high risk TT screening in
      women aged 40 years and highlights the need for a more sensitive screening test
      or a less invasive diagnostic test for the detection of Down syndrome.

PMID- 15512412
TI  - Substance abuse in an Irish antenatal population.
AB  - Substance abuse is prevalent in Ireland. The potential sequelae for abuser and
      carer are many. In pregnancy there are further problems. We assessed the
      prevalence of substance abuse in our antenatal population using an anonymous
      questionnaire and urine toxicology screening. We examined 522 women and 18 (3.4%)
      had positive urine toxicology. The anonymous questionnaire failed to identify all
      of these women. No typical patient profile emerged when the demographic features
      were studied. We believe that our study has underestimated the true prevalence of
      substance abuse in our antenatal population and many factors may have contributed
      to this. Substance abuse in pregnancy remains a difficult problem to quantify and
      for the future the main focus of attention must be on education and prevention.

PMID- 15512413
TI  - Is fetal gender significant in the perinatal outcome of pregnancies complicated
      by placental abruption?
AB  - Seventy cases of placental abruption were studied. These occurred in 12,800
      deliveries, an incidence of 4.8 per 1000. There were more female infants (34-56%)
      compared with males (27-44%). Sixteen infants were stillborn and one baby died in
      the neonatal period. Thirteen of the perinatal deaths occurred in male infants.
      We speculate that a higher metabolic rate in male infants may account for this
      sex difference.

PMID- 15512414
TI  - Early pregnancy assessment; a role for the gynaecology nurse-practitioner.
AB  - Recent improvements in the investigation of bleeding and pain in early pregnancy
      has led to simplified clinical guidelines. These in turn have created the
      opportunity for nurse-led early pregnancy assessment. We arranged for a
      gynaecology nurse-practitioner with experience to undergo additional training in
      early pregnancy care. She then took over the daily running of the Early pregnancy
      assessment centre (EPAC). A review of 200 consecutive cases showed that the nurse
      followed the guidelines extremely closely in terms of categorisation of patients,
      referral to the medical team for further investigation and selection of women who
      required anti-Rh(D) immunoglobulin. In addition, in the first 6 months of the
      clinic no cases of ectopic pregnancy were overlooked by the nurse-practitioner.
      Sixty-one per cent of the women attending the clinic did not need to see a
      doctor.

PMID- 15512415
TI  - Comparative maternal lactate-pyruvate ratios in singleton and twin pregnancies
      and in babies delivered at term.
AB  - The lactate-pyruvate (L/P) ratio was used for assessment of anaerobic metabolism,
      hypoxia or oxygen debt in uterine contractile muscle during labour and
      immediately after parturition. The mean blood lactate level was significantly
      higher in mothers with twin pregnancies (P<0.001) than in singleton pregnancies
      at term. L/P ratios were markedly elevated in established labour both in mothers
      of singleton as well as in mothers of twin pregnancies and were also higher in
      cord blood of the twins than those of singleton babies (P<0.001). The twins
      delivered second had higher L/P ratios (P<0.05) than the leading twins.

PMID- 15512416
TI  - Obstetric pubic symphysis arthropathy: a study of nine cases.
AB  - Nine Nigerian women who were either pregnant or recently delivered presented with
      a symptom complex comprising severe pain or tenderness over the symphysis pubis
      with ambulatory difficulty. Radiography and ultrasonography were used as
      complements to confirm diagnosis, and management was non-operative. Seven of the
      nine women recovered completely, but two died from presumed pulmonary embolism.
      There is no evidence that pelvic radiography influences diagnosis or management.
      We suggest routine thromboprophylaxis in the management of the entity and use of
      obstetric pubic symphysis arthropathy as a specific, descriptive and all
      encompassing nomenclature.

PMID- 15512417
TI  - Trial of self-administered antenatal care: maternal symphysis fundal height
      measurements.

PMID- 15512418
TI  - Childhood sexuality and child sexual abuse in southwest Nigeria.
AB  - There is paucity of information and research on childhood sexuality and child
      sexual abuse in Nigeria. This low level of information may not be unconnected
      with the fact that generally discussions on sexual matters still remain a taboo
      in our culture. It is almost abominable to discuss sex with children. There is
      need for a radical departure from this position in view of the fact that at least
      5% of the respondents in this study admitted having had sex between 6 and 10
      years of age and 81 respondents (2.1%) were sexually abused in childhood. The
      urgent need for more research and a multidisciplinary problem resolution approach
      to childhood sexuality and child sexual abuse is stressed.

PMID- 15512419
TI  - The modified Aldridge fascial sling (cruciate bladder sling) for genuine stress
      incontinence: a review of 50 patients.
AB  - We set out to assess the success rate and complications of the modified Aldridge
      sling for genuine stress incontinence (GSI). This was a retrospective study
      involving 50 women with urodynamically proven GSI who underwent the above
      procedure at a tertiary referral teaching hospital in Birmingham. The subjective
      cure rate at 2 years was 94%. Failures were apparent by 1 year and there were no
      recurrences by 2 years. Age, weight, parity and previous incontinence surgery did
      not make a statistical difference to the success rate. Postoperative retention
      and bacteriuria were the commonest complications. We conclude that the modified
      Aldridge sling procedure should be considered as an alternative to
      colposuspension in cases in which vaginal mobility is limited. Preoperative
      urodynamics is essential. The subjective cure rate at 2 years of 94% is
      respectable, especially when 26.8% of the patients had had at least two
      unsuccessful incontinence operations.

PMID- 15512420
TI  - Female genital mutilation - postcircumcision vulval complications in Nigerians.
AB  - Female genital mutilation is a cultural practice that can adversely affect the
      health of women. Vulval complications of female circumcision in 39 patients
      managed at the University College Hospital, Ibadan, Nigeria over a period of 10
      years were reviewed. The complications were: labial adhesions of varying degrees
      (51.3%) and clitoral retention cysts (48.7%). However, both types of
      complications occurred concurrently in two (5.1%) patients. All patients were
      treated surgically with good outcome. The only immediate complication of
      treatment was secondary haemorrhage in one patient with clitoral cyst.
      Regrettably, one patient with labial adhesion required a repeat surgical
      procedure 2 months later. The histological examination of all the retention cysts
      revealed epidermal inclusion cysts. Emphasising the reproductive health
      implications of female genital mutilation may prove an effective strategy towards
      eradication of the practice.

PMID- 15512421
TI  - Ectopic pregnancy - laparoscopic management in a district general hospital.
AB  - A 2-year retrospective study was carried out in a district general hospital to
      review the outcome of laparoscopic management versus laparotomy for the
      management of ectopic pregnancy. Outcome measures included operating time,
      postoperative analgesia requirements, complications, length of hospital stay, the
      post-ectopic intrauterine pregnancy rates and the recurrent ectopic pregnancy
      rates over an observational period of 16 months. Forty-nine consecutive women
      were seen. Twenty-six were managed laparoscopically and 23 were managed by
      laparotomy. There was no significant difference between the operating times and
      complications but the laparoscopy group had significantly fewer doses of opiate
      analgesia (P<0.05), shorter length of stay (P<0.05), and significantly higher
      post-ectopic intrauterine pregnancy rates (P<0.05) compared with the laparotomy
      group. Laparoscopic management of ectopic pregnancy is a viable alternative to
      conventional laparotomy in district general hospitals.

PMID- 15512422
TI  - The management of pre-invasive cervical lesions using cryotherapy in Yaounde,
      Cameroon.
AB  - Cervical cancer is the commonest gynaecological malignancy in developing
      countries. The pre-invasive lesion often starts more than a decade before it
      becomes overt cancer. In this study most patients were in their third or fourth
      decade of life and had been pregnant at least once. Cryotherapy has been shown in
      this study to be an effective method of treating pre-invasive lesions. The cure
      rate after 1 year follow-up following single treatment was 93.1%. Follow-up
      visits are important and can improve the results to near perfection if patients
      are properly selected for such conservative management. The complication rate of
      cryotherapy is low and mainly involves excessive mucoid discharge which lasts for
      a few weeks. It is our opinion that the technique be popularised in developing
      countries, as a cost-effective method for the management of pre-invasive lesions.

PMID- 15512423
TI  - Malignant mixed mesodermal tumour of the ovary: clinicopathological features.
AB  - Malignant mixed mesodermal tumours of the ovary have been described together with
      a literature review. The characteristic histological pictures of the various
      representative tissue elements have been demonstrated and patients
      characteristics analysed in detail. This confirms the classical features of this
      group of advanced ovarian malignancy that highlight the aggressive nature of the
      tumour associated with poor survival. Although generally they are managed in the
      same line as epithelial ovarian carcinomas the appropriate treatment has yet to
      be established. Because of their rarity they also illustrate the potential
      problems of instituting prospective randomised controlled trials.

PMID- 15512424
TI  - Complications of unopposed oestrogen following radical surgery for endometriosis.
AB  - Four cases are presented here of patients who had total abdominal hysterectomy
      and bilateral salpingooophorectomy for severe endometriosis. All were eventually
      placed on unopposed oestrogen replacement therapy, two immediately and the other
      two after a few months. All subsequently developed recurrence of their
      endometriosis whilst on oestrogen therapy, one developing an endometroid
      carcinoma. All required surgery and three were placed on continuous
      oestrogen/progestogen preparation or alternatively tibolone (which has
      oestrogenic, progestogenic and androgenic properties) postoperatively. No further
      recurrence of their disease occurred. The literature was reviewed regarding
      oestrogen therapy for women who have had bilateral oophorectomy. There were
      various suggestions as to management but no report on using continuous oestrogen/
      progestogen or tibolone. We suggest this as a logical form of replacement therapy
      for patients who have bilateraloophorectomy for severe endometriosis, as
      unopposed oestrogen therapy can cause recurrence.

PMID- 15512425
TI  - Not just a cervical ectropion. Three case reports of diethylstilbestrol (DES)
      exposed women presenting with vaginal discharge and cervical ectropion.
AB  - Typical changes in the cervix are described in three women following in utero
      exposure to diethylstilbestrol. It is important that these changes are recognised
      on colposcopy and appropriate follow-up colposcopy arranged. In the absence or
      cervical intraepithelial neoplasia, local destructive therapy is not indicated as
      this may be associated with cervical stenosis.

PMID- 15512426
TI  - Blood transfusions in gynaecology.

PMID- 15512427
TI  - Maternal common variable immunodeficiency and pregnancy.

PMID- 15512428
TI  - The use of magnetic resonance cholangiopancreatography in the management of
      biliary tract disease in pregnancy.

PMID- 15512429
TI  - Caesarean section scar dehiscence following vaginal delivery.

PMID- 15512430
TI  - Prenatal ultrasound diagnosis of a large epignathus.

PMID- 15512431
TI  - Pregnancy during postoperative management of virilising arrhenoblastoma.

PMID- 15512432
TI  - Symphysiotomy in shoulder dystocia.

PMID- 15512433
TI  - Multiple fetal anomalies: an extreme case of amniotic band syndrome.

PMID- 15512434
TI  - Face presentation caused by a short umbilical cord round the fetal neck.

PMID- 15512435
TI  - Potentially dangerous complication of an ineffective shelf pessary.

PMID- 15512436
TI  - Laparoscopically managed bilateral benign ovarian cysts in an 85-year-old woman.

PMID- 15512437
TI  - Primary malignant lymphoma of the uterine cervix: difficulties in diagnosis.

PMID- 15512438
TI  - Primary malignant melanoma of the cervix uteri.

PMID- 15512439
TI  - Primary carcinoma of the peritoneum masquerading as ovarian malignancy.

PMID- 15512440
TI  - Bilateral primary ovarian leiomyoma: a rare cause of ovarian tumour in a young
      woman.

PMID- 15512441
TI  - Advanced heterotopic pregnancy.

PMID- 15512442
TI  - Placental site trophoblastic tumouran unusual cause of intermenstrual bleeding.
      Management and 1 year of follow up.

PMID- 15512444
TI  - Endometrial stromal sarcoma.

PMID- 15512443
TI  - Vaginal carcinoma presenting as a surgical emergency.

PMID- 15512450
TI  - Paget's disease of the vulva.

PMID- 15512452
TI  - Critical appraisal workshops to promote evidence-based healthcare.
AB  - We evaluated the effect of literature appraisal workshops on participants views,
      attitudes and knowledge about evidence-based medicine in the West Midlands region
      in 1998. The performance of 55 practitioners was evaluated, before and after
      attending the workshop. After attending the workshop, participants paid more
      attention to the study design (81% vs. 98%, P=0.02), they did not find research
      evidence confusing (35% vs. 52%, P=0.05), and they felt more confident in
      assessing research evidence (26% vs. 59%, P=0.0001). Their mean knowledge scores
      improved from 47.3 (SD12.2) to 57.9 (SD 9.0) ( P=0.0001). Our critical appraisal
      skills workshops improved attitudes and knowledge needed for the provision of
      evidence-supported healthcare. Such workshops should be incorporated in
      postgraduate obstetrics and gynaecology training programmes.

PMID- 15512454
TI  - Outcome of pregnancy following renal transplantation.
AB  - Fertility is restored following renal transplantation, and the potential for
      motherhood can be realised. This retrospective study reviews the outcome of 53
      pregnancies, in 24 patients, between 1988 and 1995. All patients underwent
      transplant surgery, and received antenatal care at a single centre. The mean age
      at first conception was 27.6 years, and graft function, as assessed by serum
      creatinine at the time of antenatal booking, was good. Patients were referred
      early, seen regularly, and had both obstetrician and nephrologist involved in
      management. The main maternal complication was hypertension, affecting 50% of
      patients. Seven patients had a worsening of pre-existing hypertension, whilst
      four patients developed hypertension for the first time during pregnancy. Graft
      function was, for the most part, well maintained. Four patients required delivery
      because of declining renal function, two of these went on to develop frank
      rejection, necessitating a return to dialysis within 3 months of delivery. These
      figures however are not higher than have been reported in the non-pregnant
      population. The overall pregnancy loss was 26%. There were a total of 39 live
      births. Premature birth was higher than that of the general population, with 57%
      of infants in the study delivering before 37 weeks' gestation (average 34 weeks'
      gestation) Of the 39 infants born alive 27% were growth retarded. Congenital
      abnormalities were, reassuringly, no higher than that in the general population,
      despite the need to take immunosuppressive drugs. Delivery was by caesarean
      section in 64% of cases, which may reflect a high degree of clinical caution in
      this group of patients. The study concludes that, whilst risks are recognised,
      for both the mother and infant, with a careful, multidisciplinary approach, the
      outcome is generally good.

PMID- 15512456
TI  - The effect of maternal exercise on umbilical artery blood flow in pregnancy
      induced hypertension.
AB  - Seventeen in-patients with pregnancy-induced hypertension (PIH) in the last
      trimester of pregnancy underwent an exercise stress test. The mean exercise
      intensity achieved was 66% (55-77%) of submaximal exercise. The mean maternal
      heart rate rose significantly from a mean of 89 beats per minute (64-110 bpm) to
      a mean of 144 bpm (120-168 bpm) after exercise. The mean systolic blood pressure
      rose significantly from a mean of 149 mmHg (130-170 mmHg) to a mean of 171 mmHg
      (150-190 mmHg). The diastolic blood pressure rose from a mean of 102 mmHg (100
      110 mmHg) to a mean of 106 mmHg (100-115 mmHg). In patients with systolic blood
      pressure of 180-190 mmHg, their fetuses had significantly higher
      systolic/diastolic (S/D) ratios before and after exercise than those with blood
      pressure of 150-170 mmHg. The PI showed sharp fluctuations but the changes were
      not significant. The mean S/D and the PI decreased at 2, 4, 6 and 8 minutes of
      recovery from baseline values at rest. Subsequently it rose significantly to peak
      at 20 minutes of recovery. No evidence of ill effect from the exercise test was
      noted on any of the mothers or their fetuses. All pregnancies resulted in a good
      outcome.

PMID- 15512458
TI  - Obstetric outcome in women over the age of 40 years.
AB  - This is a retrospective review of 109 deliveries during a 5-year period in women
      aged 40 years or over and the results were compared with other studies in
      literature. The incidence was 1%. There was no increase in complications of
      pregnancy though there was an increased caesarean section rate and perinatal
      mortality rate. It is imperative that all mature pregnant women are managed as a
      high risk group but we should be mindful of the need to justify intervention in
      the same way as in the younger age group.

PMID- 15512459
TI  - Women with placenta praevia and antepartum haemorrhage have a worse outcome than
      those who do not bleed before delivery.
AB  - We set out to assess the maternal and neonatal outcomes of women with placenta
      praevia and antepartum haemorrhage (APH) between 1991 and 1997, compared with
      woman with a diagnosed placenta praevia who did not bleed. The demographic data,
      maternal and perinatal outcomes of 159 women with antepartum haemorrhage were
      compared with 93 women without antepartum haemorrhage in a retrospective study.
      Women with antepartum haemorrhage had the diagnosis of placenta praevia confirmed
      at an earlier gestation. More women with antepartum haemorrhage received
      antenatal steroids and tocolytic agents, and had emergency caesarean sections.
      The majority of women with bleeding had an emergency caesarean section for
      antepartum haemorrhage and more delivered early because of fetal distress. There
      were more preterm deliveries in women with antepartum haemorrhage. The mean birth
      weight was 2.69 kg in the women with antepartum haemorrhage and 3.06 kg in those
      without. More infants in the bleeding group had a low Apgar score at the first
      minute, respiratory distress syndrome, and admission to special baby care and
      neonatal intensive care unit. It is concluded that there is an increased risk of
      premature delivery in women with antepartum haemorrhage and placenta praevia.
      Aggressive management, tocolysis and cervical cerclage should be explored further
      to improve the perinatal outcome. Women without antepartum haemorrhage can be
      managed on an outpatient basis.

PMID- 15512461
TI  - Socioeconomic barriers to safe motherhood among booked patients in rural Nigerian
      communities.
AB  - This study examines the socioeconomic barriers to safe motherhood in booked
      patients in the Ife-Ijesha health administrative zone, Nigeria. During the period
      of study (January 1998 to December 1998), 161 booked patients of Ife State
      Hospital, Ile-Ife and Wesley Guild Hospital, Ilesha presented with an avoidable
      obstetric emergency, Seventeen (10.6%) presented during the antenatal period,
      while 89 (55.3%) and 55 (34.2%) presented in labour and postpartum respectively.
      The patients presented with obstetric complications such as obstructed labour
      (24.2%), postpartum haemorrhage (21.1%), puerperal sepsis (24.2%), imminent
      eclampsia and eclampsia (15.5%), retained second twin (9.3%). Three maternal
      deaths occurred (MMR 1467/100 000 births) and the perinatal mortality rate was
      290/1000 total births. The adduced reasons for late presentation included,
      financial constrains (85.1%), poor access to hospital/transportation difficulties
      (33.5%), objection to hospital admission by relatives (23.0%), aversion to
      caesarean section (21.7%) and attitude to hospital staff (8.1%). The patients
      were of the opinion that reducing the economic burden associated with hospital
      fee, provision of transportation, encouraged family support and reduction of
      operation rate would lead to reduction in late presentation.

PMID- 15512462
TI  - Headache following parturition.
AB  - The incidence of headache following childbirth in 226 Nigerian women is 24.3%
      (n=55) or one in four births. Headache was more prevalent among women aged
      between 21 and 30 years (n=44); those of social class 3-5 (n=50); and also
      increased incidence with increasing parity, although these relationships did not
      reach significance. There is a highly significant association between the
      incidence of postparturition headache and evidence of stress (P=0.004), but not
      with a history of migraine (p=0.102). A highly significant association also
      exists between the incidence of postparturition headache and anaemia (Hb value
      less than 10 g/dl (68%), (p=0.004). Headache started on the day of delivery in
      the majority of cases (36.4%; n=20) although the median number of days of onset
      after delivery was 2 days. Post-natal headache may be associated with some
      underlying sociomedical factors which may be influenced by the fall in pregnancy
      hormones following parturition.

PMID- 15512464
TI  - Aetiology and management of the secondary brow.
AB  - The finding that a brow presenting within the pelvic cavity in the mento-anterior
      position during the second stage of labour could be easily and safely delivered
      by means of Kielland's forceps rotation and extraction led to a search for the
      cause of this rare phenomenon since normally brows are associated with non
      engagement of the head. A personal series of six cases, collected over 39 years,
      were studied. Particular attention was paid to pelvic size and shape with
      detailed X-ray pelvimetry being obtained in the puerperium from the latter three
      patients. In all cases the pelvises were found to be commodious and, in the three
      where X-ray pelvimetries were taken, they were found to be anthropoid in shape,
      which is known to favour the occipito-posterior position. Past and subsequent
      pregnancies conducted by the author were in every instance associated with an
      occipito-posterior position, and a mechanism of labour for secondary brow
      presentations until impasse occurred was suggested. It was concluded that the
      condition only occurred when the pelvis was roomy and anthropoid in shape, and,
      for those experienced in their use, Kielland's forceps rotation and extraction
      was preferable to caesarean section. Furthermore, aficionados of the ventouse
      were warned to avoid attempting delivery with that instrument for such would be
      doomed to failure.

PMID- 15512465
TI  - Caesarean morbidity and mortality at Maiduguri, Nigeria.
AB  - A total of 2456 deliveries took place at the University of Maiduguri Teaching
      Hospital, Maiduguri, between January 1995 and December 1996 inclusive. Two
      hundred and five women were delivered by caesarean giving a caesarean section
      rate of 8.3%. One hundred and ninety-eight (96.6%) case records were retrieved
      for analysis. Eighty-eight patients (44.4%) had one or more intra- and/or
      postoperative complications. Sepsis was the commonest complication involving 62
      (70.4%) women. All were cases of emergency caesarean section. The incidence of
      other complications were anaemia, 59 (67%); hemorrhage, 38 (43.2%); and wound
      dehiscence, 11 (12.5%). There were two maternal deaths (2.3%) due to an
      anaesthetic accident and septicaemia respectively. The factors resulting in
      complications of the caesarean deliveries were prolonged obstructed labour,
      prolonged rupture of fetal membranes, previous caesarean sections, antepartum
      haemorrhage and severe pre-eclampsia and eclampsia. A review of the use of
      prophylactic antibiotics in selected cases, early recourse to operation in cases
      with cephalo-pelvic disproportion, and the acquisition of trained anaesthetists
      are advocated.

PMID- 15512467
TI  - Risk of spontaneous abortion following induced abortion is only increased with
      short interpregnancy interval.
AB  - We set out to study the risk of spontaneous abortion following a first trimester
      induced abortion as a function of the interpregnancy interval between two
      pregnancies. The cohort study is based on the following databases: Danish
      national registries: the Medical Birth Registry (MBR), the Hospital Discharge
      Registry (HDR), and the induced Abortion Registry (IAR). All primigravid women in
      the time period from 1980 to 1982 were identified in the MBR, the HDR and the
      IAR. A total of 15 727 women who terminated the pregnancy with a first trimester
      induced abortion were selected as the induced abortion cohort, and 46 026 women
      who did not terminate the pregnancy with an induced abortion constituted the
      control cohort. By register linkage all subsequent pregnancies which were not
      terminated by induced abortion were identified from 1980 to 1994. Only women who
      had a non-terminated pregnancy following the index pregnancy were selected. Women
      whose first pregnancy was terminated following a first trimester induced abortion
      had a risk of spontaneous abortion of 11.0% vs. 9.4% in the control cohort. This
      relative difference of 1.17 was not statistically significant in logistic
      regression analyses. An increased risk was only found for women who had an
      interpregnancy interval of less than 3 months (OR=4.06, 95% C.I.=1.98-8.31). The
      abortion method, vacuum aspiration with dilatation or evacuation with dilatation
      did not modify this elevated risk. Overall the study did not show an increased
      risk of spontaneous abortion following one or more induced abortions, except for
      women with a short interpregnancy interval between an induced abortion and a
      subsequent pregnancy. We recommend women who have a first trimester induced
      abortion be advised to wait at least 3-6 months before trying to become pregnant
      again.

PMID- 15512468
TI  - Pattern of morbidity and mortality following illegal termination of pregnancy at
      Nnewi, Nigeria.
AB  - Seventeen women were treated for complications of illegal termination of
      pregnancy over a 2-year period, January 1996 to December 1997. Important
      characteristics of the women include a mean age of 21 years (mode 18 years) and
      being unmarried (100%, n=17), nulliparous (94%, n=16) and unemployed (76%, n=13).
      There was a tendency towards late termination as 50% of women had a termination
      after 13 weeks. Serious complications were cervical laceration, pelvic
      abscess/peritonitis, ruptured uterus, transection of the sigmoid colon and
      ileal/jejunal lacerations. The mortality rate was 6% (n=1). Most of the
      terminations were performed through instrumental cervical dilatation without
      prior medical or hydrophilic treatment. This study shows that illegal abortions
      are still commonly performed in Nigeria with an unacceptably high incidence of
      morbidity and mortality. Modernisation of abortion laws, wider contraceptive
      usage, adoption of modern methods of termination of pregnancy (RU 486 and
      prostaglandin E(1) analogues) and prophylactic antibiotics are recommended in
      order to reduce the problems of unsafe abortion in Nigeria and other developing
      countries.

PMID- 15512469
TI  - Sacrospinous colpopexy at vaginal hysterectomy: method, results and follow up in
      75 patients.
AB  - This study reviews our experience with sacrospinous colpopexy done at the time of
      vaginal hysterectomy over a period of 3 years, and discusses the indications,
      outcome and safety of the technique. Between January 1996 and December 1998, 75
      patients had sacrospinous colpopexy at the time of vaginal hysterectomy. The mean
      age of patients was 57.1 years. Simultaneous bilateral vaginal oophorectomy was
      done in 36 patients, anterior colporrhaphy in 56, and posterior colporrhaphy in
      24. All patients underwent perineorrhaphy. Dissection and obliteration of the
      enterocoele sac was performed whenever encountered. Patients were seen at 2, 6
      and 12 months following surgery and then yearly thereafter. The mean operative
      time was 85 minutes, mean uterine weight was 101 grams and mean blood loss was
      137 ml. The mean follow-up period was 15 months. The vaginal vault remained well
      supported in 96.7%, with recurrent cystocoele in six patients (9.8%), recurrent
      rectocoele in 1.3%, and shortvagina in 3.3%. At 1-year follow up, 28% of those
      who were sexually active prior to surgery reported an improvement in sexual
      function. When dealing with uterovaginal prolapse, sacrospinous colpopexy
      performed at the time of vaginal hysterectomy is an effective treatment option
      for vaginal vault support.

PMID- 15512470
TI  - Are the immediate complications of conisation with the large loop similar to
      those with the knife?
AB  - One hundred patients underwent conisation with large loop excision of the
      transformation zone. The overall immediate complication rate was 6%. There were
      no preoperative complications. Three patients were treated with antibiotics for
      infection and three patients had a secondary haemorrhage. No patient required a
      blood transfusion or cervical suturing and no patient returned to the operating
      theatre.

PMID- 15512471
TI  - Can a single serum CA125 assay predict the outcome of threatened abortion?
AB  - Earlier work suggested that high levels of CA125 could be detected in the sera of
      women with threatened abortion. In this study, we used CA125 as a method of
      anticipating outcome in cases of threatened abortion and compared the results
      with ultrasonic findings. Three groups of patients were studied.(1) 57 women who
      threatened to abort, but whose pregnancy continued.(2) 43 women with a threatened
      abortion, who subsequently aborted, and (3) 50 normal women who had no bleeding
      in early pregnancy. There was a highly significant increase in serum CA125 in
      women who aborted compared with the other two groups (P<0.001). The results
      compared well with conventional ultrasound and serum CA125 may be developed as a
      cheap, sensitive and specific predictor of outcome in cases of threatened
      abortion.

PMID- 15512472
TI  - Fertility regulatory methods and development of complications after evacuation of
      complete hydatidiform mole.
AB  - In a prospective, simple randomised study, we evaluated the relative efficacy of
      hormonal (oral contraceptive pill) and non-hormonal (intrauterine contraceptive
      device) methods of contraception as fertility regulatory agents in patients with
      complete hydatidiform moles and assessed the development of complications and
      sequelae if any, following their use. Fifty-six patients each on oral
      contraceptive pills (OCP) and intrauterine contraceptive device (IUCD) were
      recruited into the study. Ten patients, six on OCP and four on IUCD discontinued
      for varying reasons. Five patients (two on OCP, and three on IUCD) developed a
      gestational trophoblastic tumour and were admitted for chemotherapy. There was no
      complication attributable to any of the methods.

PMID- 15512473
TI  - Outcome following subtotal hysterectomy.
AB  - Approximately 20% of women in the United Kingdom have a hysterectomy by the age
      of 60 years for various reasons, usually a total hysterectomy. This modern
      hysterectomy was introduced in order to prevent the occurrence of cervical stump
      carcinoma. The incidence of cervical stump carcinoma is low and with the advent
      of Papanicolaou smears have been negligible. Many gynecologists and patients
      worldwide have questioned the routine removal of the benign cervix, as the
      argument for conserving the cervix is less disturbance to bladder, bowel and
      sexual function. This study was undertaken to review the long-term outcome after
      subtotal hysterectomy.

PMID- 15512474
TI  - Current trends in management of ectopic pregnancy in the United Kingdom.
AB  - The potential advantages of laparoscopic management of ectopic pregnancy include
      lower morbidity, faster return to work, and less impact on reproductive health.
      This study aimed to investigate the current management of ectopic pregnancy in
      the United Kingdom. Thirty-five per cent of ectopic pregnancies are currently
      managed laparoscopically. Units that tended to operate laparoscopically were more
      likely to attempt to preserve the fallopian tube at surgery. Ninety per cent of
      units in the UK feel that they potentially could manage ectopic pregnancies
      laparoscopically but in practice only 60% managed any of the last three ectopic
      pregnancies by this technique.

PMID- 15512475
TI  - Effects of Seprafilm (sodium hyaluranate-based bioresorbable), Sepracoat (0.4%
      hyaluronic acid), and Ringer's lactate on the prevention of postsurgical adhesion
      formation in rat models.
AB  - Forty adult female rats were randomly divided into four groups. Before the
      standard surgical procedure which consisted of creating a lesion with a lancet
      over the right uterine horn. Group I received no medication. Ringer's lactate
      (RL) solution was applied intraperitoneally to Group II at the end of the
      surgery. Sepracoat solution was applied intraperitoneally to Group III at the
      onset of the surgery. Group IV randomly received Seprafilm wrapped over the
      entire right uterine horn. Re-laparotomy was performed 3 weeks later to evaluate
      the adhesions. The mean adhesion scores were (mean+/-SD) 2.90+/-0.18, 1.00+/
      0.36, 0.50+/-0.17 and 0.40+/-0.16 in Groups I, II, III, IV, respectively. The
      postsurgical adhesions were significantly less in the groups treated with
      Seprafilm and Sepracoat.

PMID- 15512476
TI  - Anxiety and outpatient hysteroscopy.

PMID- 15512477
TI  - Modified technique of transabdominal cerclage in cervical pregnancy.

PMID- 15512479
TI  - Congenital antithrombin III deficiency in pregnancy treated with low-molecular
      weight heparin.

PMID- 15512478
TI  - Sleep apnoea syndrome in pregnancy without fetal compromise.

PMID- 15512480
TI  - Juvenile fibroadenoma during pregnancy.

PMID- 15512481
TI  - Triplets delivered vaginally.

PMID- 15512482
TI  - Axial rotation of the non-gravid uterus through 1080 degrees (3 x 360 degrees ).

PMID- 15512483
TI  - Pregnancy following endometrial ablation.

PMID- 15512484
TI  - Placental chorioangioma as a cause of maternal hydrops syndrome.

PMID- 15512485
TI  - Umbilical cord thrombosis-a cause of intrauterine demise?

PMID- 15512486
TI  - Prenatal ultrasound diagnosis of isolated conotruncal anomalies.

PMID- 15512487
TI  - Prune belly syndrome co-existing with the VACTERL-complex in a background of
      antenatal ingestion of traditional concoction.

PMID- 15512488
TI  - Laparoscopic removal of an ectopic uterus in a patient with Mayer-Rokitansky
      Kuster-Hauser syndrome.

PMID- 15512489
TI  - Rokitansky-Kuster-Hauser syndrome associated with chromosomal abnormality and
      fibroid arising from the rudimentary uterine horn.

PMID- 15512490
TI  - Trichoepithelioma of the vulva.

PMID- 15512491
TI  - Recurrent ovarian cancer invading small bowel and presenting with melaena.

PMID- 15512492
TI  - Uterine leiomyomata causing tubal occlusion.

PMID- 15512494
TI  - Annual meeting of the Northern Obstetrical and Gynaecological Society, Conference
      Hall, Victoria Hospital, Kirkcaldy, Scotland, 28 May 1999.

PMID- 15512493
TI  - Vulvar cancer in pregnancy.

PMID- 15512496
TI  - Audit standards in ectopic pregnancy.
AB  - Due to a combination of increasing public awareness and improved diagnostic
      techniques, women now present to the clinician early in pregnancy. The majority
      of women with an ectopic pregnancy are haemodynamically stable. This enables the
      gynaecologist to consider several management options, such as expectant, medical
      or laparoscopic surgical treatment rather than just the conventional open
      surgical approach. This review article examines current literature on the
      management of ectopic pregnancy and proposes audit standards to be used in the
      diagnosis and optimal treatment of ectopic pregnancy. It is hoped that this would
      then enable meaningful audit and review of current clinical practice, leading to
      improved patient outcome.

PMID- 15512497
TI  - Endometrial resection and subsequent pregnancy.

PMID- 15512498
TI  - Re-evaluation of plasma creatinine concentration in normal pregnancy.
AB  - Renal function improves during pregnancy, a well-known clinical manifestation of
      this being a fall in plasma creatinine concentration. However, there are no
      secure data upon which to determine the extent to which creatinine concentration
      changes during pregnancy. A well-defined reference range is important for the
      correct interpretation of results, but to date one has not been published. This
      study uses a large cohort of women experiencing normal pregnancy, modern
      laboratory technique and robust statistical analysis to construct a cross
      sectional reference interval. This study shows that the upper limit of normal for
      creatinine in pregnancy is higher than previously suggested, although still much
      lower than outside pregnancy. Values for the upper limit of normal can be taken
      as 85 micromol/l, 80 micromol/l and 90 micromol/l in the first, second and third
      trimesters of pregnancy respectively. This information is important for the
      clinical assessment of a result from a pregnant woman, particularly in conditions
      such as pre-eclampsia where abnormalities of renal function may occur.

PMID- 15512499
TI  - The experience with prostaglandin E2 vaginal tablets for induction of labour in
      grand and great grand multiparae. A two year review in Saudi Arabia.
AB  - In an attempt to review our experience with prostaglandin E2 vaginal tablets in
      induction of labour in grandmultiparae (parity 5-9) and great grandmultiparae
      (parity > 9) a retrospective study was carried out at King Faisal Military
      Hospital in Saudi Arabia over a 2-year period. An evaluation of our protocol for
      induction of labour using prostaglandin in these groups of patients was also
      made. The patients included 271 grandmultiparae and 63 great grandmultiparae.
      There were no serious side effects in our series referable to the prostaglandin
      induction. There were no significant differences in the two groups regarding the
      mean total dose of prostaglandin used, mean length of second stage of labour,
      mean birth weight and admission to the neonatal intensive care unit (P > 0.05).
      However, the need for syntocinon augmentation was more in the great
      grandmultiparae (29% vs. 19%) but this was not significant statistically (P =
      0.64). The caesarean section rate was higher in the great grandmultiparae (14%
      vs.10%) but not statistically significant (P = 0.19). None of the babies in the
      study group had an Apgar score less than 7 at 5 minutes. This study has shown
      that it may be safe to use prostaglandin E2 vaginal tablets for induction of
      labour in grandmultiparae and great grandmultiparae in our environment although
      the sample size may not be large enough to draw definite conclusions. Our
      protocol of stepwise increase in prostaglandin dose did not increase maternal or
      fetal morbidity but might actually have reduced the number of caesarean sections
      performed and therefore maternal mortality associated with caesarean section in
      the grandmultiparae. A multicentre prospective trial is eagerly awaited.

PMID- 15512500
TI  - The value of serum fructosamine in comparison with oral glucose tolerance test
      (OGTT) as a screening test for detection of gestational diabetes mellitus.
AB  - The objective of this study was to evaluate the effectiveness of a single assay
      of serum fructosamine as a screening test for gestational diabetes in comparison
      with the oral glucose tolerance test. A cross-sectional descriptive study was
      performed on 210 pregnant women attending antenatal clinics at Colombo South
      Teaching Hospital. A 75 g oral glucose tolerance test and serum fructosamine
      assay in the fasting state and 2 hours after ingestion of oral glucose was
      performed. The statistical significance of fructosamine values were assessed by
      Student's t-test and the reliability of the test was assessed by calculating the
      sensitivity and specificity. There was no significant difference in serum
      fructosamine levels when measured fasting and 2 hours after ingestion of 75 grams
      of glucose. In comparison with 75 g glucose tolerance test single assay of serum
      fructosamine gave a sensitivity of 87.5% and a specificity of 94.5% with regard
      to detection of gestational diabetes mellitus. Therefore a single assay serum
      fructosamine test at any time of the day can be recommended as a screening test
      for detection of gestational diabetes mellitus.

PMID- 15512501
TI  - The effect of superstition on the day of discharge from maternity units in
      Northern Ireland: "a Saturday flit is a short sit".
AB  - The impetus for evidence-based practice arose from the science of maternity and
      childcare. Yet this has to coexist with patient preferences which are often based
      on a belief system far removed from science. This paper shows how a superstition,
      which suggests that moving on a Saturday is unlucky, affects a large proportion
      of discharges from maternity units in Northern Ireland. This is a descriptive
      study of the 77 018 patients admitted to maternity units in Northern Ireland
      between 1994/95 and 1996/97. Overall 3819 (35.7%) fewer patients than expected
      were discharged on Saturday and 2445 (23.2%) and 1834 (17.4%) more than expected
      were discharged on Friday and Sunday respectively. This means that at least 8097
      patients were probably affected by the superstition. In an evidence-based world
      patient preferences are still evident.

PMID- 15512502
TI  - Stillbirths in Qatar: a review of 83 cases.
AB  - To evaluate the aetiology, diagnostic procedures and current management of
      stillbirths in Qatar, 83 stillbirths with a birth weight of more than 500 g were
      studied. The validity of the cause of death was classified as certain, probable
      and unexplained. Frequency and descriptive statistics were used. The stillbirth
      rate was 8.15 per 1000. The cause of death was certain in 29%, probable in 62%
      and remained entirely unexplained in 9% of the cases. The major factors that
      might be the causes of fetal death were intrauterine growth retardation (23%),
      abruptio placentae (16.3%), congenital anomalies (13.3%), gestational diabetes
      (9.6%) and hydrops fetalis (7.2%). The cause of death was found unavoidable in 24
      cases (29%). The autopsy rate was terribly low (1/80) and far away from the
      recommended rate of 75%. The introduction of a stillbirth programme, that
      includes post-mortem autopsy, in any maternity hospital, is considered crucial to
      reach a specific diagnosis for almost all stillbirths and to prevent fetal death
      in future pregnancies. However, if the patient or her family refused autopsy, a
      combination of patience and learned communication can pave the way to their
      understanding and acceptance of the procedure. Postmortem magnetic resonance
      imaging may be used as alternative to autopsy if it is refused.

PMID- 15512503
TI  - Undiagnosed breech in Zaria, Nigeria.
AB  - There is no certainty about the best way of dealing with a breech presentation
      first diagnosed in labour. In our unit, the decision to allow a trial of vaginal
      delivery rested on the clinical assessment of the size of the baby and the
      maternal pelvis, and the progress of labour. We compared the outcome of 32 cases
      where a breech presentation was first diagnosed in labour with 65 women where the
      malpresentation was diagnosed antenatally where a full assessment including
      ultrasound and radiological pelvimetry could be made. There was no significant
      difference in the mode of delivery and fetal outcome. We continue to favour
      careful case selection for vaginal delivery even where the breech is first
      diagnosed in labour.

PMID- 15512504
TI  - Obstructed labour - a preventable entity.
AB  - We present a clinical study of 204 cases of obstructed labour admitted over a
      period of 5 years between 1991-92 and 1996-97 in a rural institute in central
      India. They constituted 1.9% of births. Seventy-one per cent of the cases were
      from the rural area (similar to the overall patient population in this hospital),
      31.4% women were primigravidae. Of the subjects, 64.7% were between 20 and 29
      years. Malpresentation was the cause in 53.2%, followed by cephalopelvic
      disproportion, in 41.1%. Intraoperative incomplete rupture was detected in 5.9%
      cases. The commonest maternal morbidity was intraoperative extension of uterine
      incision at the time of caesarean section, mostly lateral (14.0%). Of the women,
      12.5% had intrapartum or postpartum sepsis. The perinatal mortality was 160/1000.
      There was no maternal mortality. Timely diagnosis of malpresentation, pelvic
      contraction and use of a partogram at all levels could have prevented obstructed
      labour. In these unfortunate situations, judicious selection of subjects for
      caesarean section is appropriate, avoiding heroic vaginal procedures even with a
      dead baby. Infection devitalises tissues and attempts at vaginal delivery may be
      dangerous.

PMID- 15512505
TI  - Uterine rupture as seen in the University of Calabar Teaching Hospital, Nigeria:
      a five-year review.
AB  - Eighty-five cases of uterine rupture were seen and managed in the University of
      Calabar Teaching Hospital, Nigeria, within a 5-year period from 1986 to 1990. The
      total number of deliveries during the period was 10 247 giving an incidence of
      0.83% uterine rupture or 1 in 121 deliveries. About 82% of the cases occurred
      within the age range of 20-30 years. The highest incidence of uterine rupture was
      seen in Para 5 and four cases of uterine rupture occurred in primigravida.
      Abdominal tenderness was the commonest clinical feature in this series. Anterior
      uterine rupture occurred in almost 60% of the cases managed. Rupture of the
      unscarred uterus was seen in 58.5% of the cases with the majority being due to
      cephalopelvic disproportion. Four cases of traumatic rupture were identified; one
      of which was due to road traffic accident. Repair of uterine rupture with
      sterilisation following active resuscitation was the commonest surgical procedure
      employed and was not associated with any maternal mortality. Associated maternal
      and perinatal mortalities were 9.8% and 85.4% respectively and hypovolaemic shock
      was the major cause of maternal death.

PMID- 15512506
TI  - Is breastfeeding during pregnancy harmful?

PMID- 15512507
TI  - Tension-free vaginal tape (TVT) - a new surgical procedure for female stress
      incontinence.
AB  - A new, minimally invasive procedure for female stress incontinence has recently
      been developed in which a prolene tape is placed without tension under mid
      urethra, usually using local anaesthesia and mild sedation. Post-operative
      catheterisation is not employed. Forty-two women with urodynamically verified
      severe urinary stress incontinence were operated on in 1996 and 1997. They
      underwent subjective and objective follow-up in 1998 with mean follow-up time 16
      months, range 6-27 months. The procedure was well tolerated. All patients except
      four (90.2%) were discharged within 24 hours. Subjectively, 85.4% were cured and
      a further 9.8% had slight incontinence only and used no protection. Objectively,
      80.5% were cured and 12.2% were >90% improved. There were no cases of long term
      voiding problems, recurrent urinary tract infections, de novo urge incontinence,
      or sling rejections. With medium term follow-up this procedure appears to have
      good results and few complications.

PMID- 15512508
TI  - Contraceptive intentions of women seeking induced abortion in the city of Jos,
      Nigeria.
AB  - This is a prospective study involving 120 women who requested abortion for an
      unplanned and unwanted pregnancy. We sought to determine their contraceptive
      intentions and use. The characteristics of these women revealed that the majority
      were young, single schoolgirls with 68.5% of them being nulliparous. Over 90% had
      had their first sexual experience before the age of 20 years. Although, 113 (94%)
      were aware of the availability of contraceptive services only 70 (62%) of these
      had ever used a method and the majority of the contraceptive methods selected
      were ineffective. Although 97 (80.8%) had a positive intention towards post
      abortion family planning, only 18 (18.5%) eventually agreed and were offered a
      method after the termination of pregnancy. The study revealed a high risk group
      of unplanned and unwanted pregnancy in Jos but low contraceptive use despite the
      high positive intentions expressed by this cohort of patients. Effective post
      abortion contraception counselling should be incorporated into family planning in
      Nigeria in order that clients who express positive intentions to the use of
      family planning actually use the method thereby reducing the incidence of
      repeated induced abortions and its social and medical consequences.

PMID- 15512509
TI  - Quality of information on female sterilisation on the Internet.
AB  - The Internet has a great potential to provide useful as well as useless or
      misleading information. To assess the quality of information available on-line on
      female sterilisation, we performed a search of the Internet using seven search
      engines. We set out to assess the first 10 sites found by each of the most
      frequently used search engines. Our search revealed 12 relevant Web sites, none
      of which complied with all of the criteria for quality. Our assessment focused on
      credibility and content of each Web site. Credibility was assessed by source
      which was described in nine Web sites, currency in five sites and review process
      in none. We assessed the content by hierarchy and accuracy of evidence which was
      fulfilled by five sites and one site respectively. This makes it difficult for a
      lay person to assess which Web sites provide accurate and useful information and
      which do not.

PMID- 15512510
TI  - Hysterosalpingocontrastsonography in clinical practice.
AB  - The aim of this study was to review the indication, source of referral and
      findings at hysterosalpingocontrastsonography (HyCoSy) of the first 100 patients
      referred for this new service in the gynaecological outpatients department of the
      Coombe Women's Hospital, Dublin. Of the first 100 women referred for HyCoSy, the
      indication for referral was investigation of infertility in 72%, recurrent
      miscarriage in 22% and other reasons in 6%. Sixty-four women were referred from
      general gynaecological clinics, 29 from the specialised infertility clinic and
      seven women were referred from other hospitals. The procedure was completed in
      97% of cases and tubal patency successfully assessed in 95%. Saline
      hysterosonography was performed in 96 cases. Tubal assessment with Echovistt
      showed bilateral tubal patency in 73%, bilateral occlusion in 10% and unilateral
      patency in 12%. All women were discharged within 30 minutes of the procedure. We
      concluded that hysterosalpingocontrastsonography is an easily introduced,
      successful outpatient technique, which is well tolerated by women and provides
      clinically relevant information in women with infertility or recurrent
      miscarriage.

PMID- 15512511
TI  - The value of gonadotrophin releasing hormone analogue in an intrauterine
      insemination (IUI) programme.
AB  - Gonadotrophin releasing hormone analogue (GnRHa) is widely used in in-vitro
      fertilisation programmes and has no doubt led to a significant improvement in the
      pregnancy rate as well as cycle planning. However, its use in intrauterine
      insemination (IUI) programmes remains controversial. This is a retrospective
      review of patients who received IUI treatment at our assisted conception unit,
      during a 12-month period from August 1997 to July 1998. Fifty-two patients
      underwent a total of 85 cycles. Six cycles were abandoned, five due to excessive
      response and one for continuous bleeding. They all received Nafarelin nasal spray
      from day 2 until ovulatory HCG was administered. Metrodin injection was given
      from day 3. There were 18 clinical pregnancies. Seventy-nine cycles were
      completed giving a pregnancy rate of 22.8% per completed cycle. There were five
      (27.8%) multiple pregnancies. The use of GnRHa in our programme enabled us to
      achieve a good cycle control as well as flexibility in the timing of insemination
      such that weekend work was avoided. We conclude that the use of GnRHa facilitates
      the efficiency of an IUI programme.

PMID- 15512512
TI  - Burch colposuspension: a 10 to 12 years follow up.
AB  - Burch colposuspension is considered to be the gold standard for the surgical
      treatment of genuine stress incontinence in women. Short-term cure rates are as
      high as 90%. (Jarvis, 1994). The long-term (10 or more years) cure rate of 62% in
      this study confirms the time dependent decline in efficacy.

PMID- 15512513
TI  - Tolerability and reasons for discontinuation of Norplant in an inner city
      population.
AB  - We carried out a retrospective analysis of the continuation rates of 142 Norplant
      acceptors. Follow-up data was available on 110. We assessed the relative impact
      of side effects on discontinuation. No serious complications (immediate or late)
      were observed during the 3-year study period and no pregnancies occurred. The 3
      year continuation rate was 88%. The commonest reported side effect was cycle
      disruption (64% of users). However this only accounted for 31% of
      discontinuations. This we attribute to thorough counselling about menstrual
      disruption. On the other hand androgenic side effects accounted for 12% of
      discontinuations but were experienced by 10% of users-perhaps because some users
      did not expect them. We conclude that Norplant is highly acceptable when offered
      with specialist counselling and support. Non-bleeding side effects accounted for
      relatively higher discontinuations and may need to be emphasised in counselling.
      A dedicated service enhanced acceptability.

PMID- 15512514
TI  - Patient satisfaction with the care provided at a gynaecology oncology clinic.

PMID- 15512515
TI  - On the shoulders of giants.

PMID- 15512516
TI  - Primary hyperparathyroidism in pregnancy.

PMID- 15512517
TI  - Folate deficiency in pregnancy presenting as acute megaloblastic crisis.

PMID- 15512519
TI  - Post morterm caesarean section - intervention not indecision.

PMID- 15512518
TI  - Amniotic fluid embolus following feticide - a cautionary tale.

PMID- 15512520
TI  - "Transient HELLP syndrome" followed by massive ascites.

PMID- 15512521
TI  - Severe postpartum HELLP syndrome.

PMID- 15512522
TI  - Hypercalcaemia due to metastatic melanoma during pregnancy.

PMID- 15512523
TI  - Co-existence of spontaneous rupture of uterine artery and placental abruption.

PMID- 15512524
TI  - Hip fracture during labour due to transient osteoporosis of the hip in pregnancy.

PMID- 15512525
TI  - Cardiac arrest in an obese hypertensive patient with multiple pregnancy.

PMID- 15512526
TI  - A bizarre history in a woman requesting repeat termination of pregnancy.

PMID- 15512527
TI  - Unsuspected metastatic rectal cancer presented as an abnormal cervical smear.

PMID- 15512528
TI  - Primary tubal adenocarcinoma.

PMID- 15512529
TI  - Asynchronous ovarian torsion in a patient with McCune-Albright syndrome.

PMID- 15512530
TI  - Glial polyp: an unusual cause of post-coital bleeding.

PMID- 15512531
TI  - Elevated CA125 levels in association with endometriosis.

PMID- 15512532
TI  - An unusual case of uterus didelphis resulting in misdiagnosis of tubal occlusion.

PMID- 15512533
TI  - Cyclical mucosal ulceration.

PMID- 15512534
TI  - Patient satisfaction with a ring pessary.

PMID- 15512539
TI  - The caesarean section epidemic.

PMID- 15512540
TI  - Reduced fetal movements and maternal medication - new pregnancy risk factors for
      neurodevelopmental disability in childhood.
AB  - A case-control study was undertaken of 471 children on the Nottingham Special
      Needs Register (SNR) who were born in one of the two maternity units in the city
      between 1987 and 1993 (inclusive). Controls were selected as the next infant born
      at the same hospital following each index case. The aim of the study was to
      identify risk factors on the Nottingham Obstetric Database for a baby
      subsequently appearing on the SNR. Disability was analysed by both ICD-9 coding
      and functional assessment. Factors which independently and significantly
      predicted a child's likelihood of being on the SNR were breech presentation
      (adjusted odds ratio (OR) = 4.0), congenital abnormality (OR=4.9), intrapartum
      fetal distress (OR=1.7), fetal growth restriction (OR=2.0), socioeconomic
      deprivation (OR=1.8), prematurity (OR=2.2), reduced fetal movements (OR=2.5) and
      medication in pregnancy (OR=10.4). To our knowledge the last two factors have not
      previously been reported as risk predictors for neurodevelopmental disability.

PMID- 15512541
TI  - Variations in oxytocin regimes in Scottish labour wards in 1998.
AB  - Oxytocin (Syntocinon, Sandoz Pharmaceuticals) is a commonly used drug in the
      modern management of labour. A recently published British survey found that 38%
      of low risk primigravid labours were augmented, most commonly by intravenous
      syntocinon. Unfortunately the misuse of syntocinon can lead to potentially
      serious problems for the fetus and mother. Despite the frequency of usage there
      appears to be no consensus as to the optimal dose and mode of administration.
      This paper explores the extent of this variation among Scottish obstetric units,
      the reasons for any variation in its use and makes some suggestions as to the way
      forward based on the current literature.

PMID- 15512542
TI  - One year survey of maternal mortality associated with eclampsia in Dhaka Medical
      College Hospital.
AB  - Data was collected prospectively from 763 eclamptic patients hospitalised at
      Dhaka Medical College Hospital. Comparisons were made between the patients that
      died and survivors based on determinants already known to be important. The cause
      of death was taken from the clinical history. The 'Case fatality rate' was 14.7%.
      The principle mortality risk factors were age, parity, number of convulsions and
      time between onset of convulsions and admission to hospital. Less than 10% in
      both groups had received antenatal care. The hospital mortality rate was
      significantly higher than that found in the Collaborative Eclampsia Study. Urgent
      interventions are required to increase public awareness of the need for antenatal
      care, to raise the level of understanding and improve attitudes and practice in
      relation to eclampsia.

PMID- 15512543
TI  - Pregnancy complicated by maternal cardiac disease: a review of 274 patients.
AB  - The outcome of 274 viable pregnancies in 229 patients with cardiac disease that
      delivered at the King Fahad Hospital, Al-Khobar, Saudi Arabia, between 1982 and
      1998 was reviewed. The incidence was 0.6% of deliveries. Rheumatic heart disease
      complicated 208 (75.9%) pregnancies, congenital heart lesion in 49 (17.9%) and
      the remaining 17 (6.2%) pregnancies were a miscellaneous group that included
      supraventricular tachycardia, ectopic beats, ischaemic heart disease and
      cardiomyopathies. The NYHA grading was between 1-2 in 243 (88.7%) pregnancies
      antenatally. Thirty-one patients developed heart failure, most commonly in the
      antenatal period, 29 of whom were of Grade 1-2. One mother in the series died
      from heart failure following a cesarean section. She had had a mitral valvotomy
      before pregnancy and was categorised as Grade 2, antenatally. The perinatal
      mortality rate was 14.6/1000 deliveries in the study group. Prophylactic
      antibiotics were given to all the patients an hour before delivery. There were
      two instances of bacterial endocarditis in the series.

PMID- 15512544
TI  - The rise in obstetric intervention with maternal age: a continuous phenomenon.
AB  - Population-based data from the Cardiff Births Survey has been used to examine the
      trends in obstetric intervention with increasing maternal age. As maternal age
      increases, spontaneous vaginal delivery rates fall, instrumental delivery rates,
      elective and emergency caesarean section, induction of labour and epidural rates
      rise. Induction of labour and epidural in labour are both associated with
      decreased spontaneous vaginal delivery rates and an increase in instrumental
      delivery rates and emergency caesarean section.

PMID- 15512546
TI  - Perinatal mortality in retained second twin.
AB  - Retention of the second twin is diagnosed if the twin is still undelivered 30
      minutes after the birth of the first baby and this condition constitutes an
      obstetric emergency often associated with a poor outcome. We report the causes of
      retention and the perinatal mortality rate in 30 retained second twins in a
      series of 128 sets of twin births recorded in Mansa General Hospital (Zambia)
      from 1 August 1993 to 31 July 1995. The study focused only on 125 available case
      notes. The incidence of twin birth is 4% of deliveries and 24% second twins were
      retained. The main causes of retention were uterine inertia (90%),
      malpresentation (60%) and home delivery of the first twin (23%). The perinatal
      mortality rate was higher in retained second twins (47%) than in those delivered
      normally (13%). The main factors associated with perinatal deaths were very low
      Apgar score (100%), cephalic presentation (64%) and very low birth weight (29%).
      Only good antenatal and intrapartum care can help reduce the incidence and poor
      outcome due to the retained second twin.

PMID- 15512545
TI  - Polymorphisms in glycoprotein (GP) lb alpha are not associated with adverse
      outcomes in primigravidae.
AB  - The platelet glycoprotein lb-IX complex is critical in platelet adhesion under
      conditions of high shear stress. Three genetic polymorphisms in the GPlbalpha
      subunit have been variably associated with thrombotic disorders. Women with
      serious obstetrical complications have an increased incidence of polymorphisms in
      other coagulation factors predisposing them alpha to thrombosis. Three GPlb
      variants were genotyped in 271 women in an Irish primigravid population, 258 with
      recorded outcomes, and in 22 patients with recurrent thrombosis and 15 patients
      with recurrent fetal loss. These were: the 13 amino acid variable number of
      tandem repeats (VNTR A/B/C/D), the Thr145Met antigen (HPA2) and a variant in the
      'Kozak' sequence 5 bases upstream of the methionine initiation codon (T-5C). The
      VNTR B and HPA2b (145Met) alleles were strongly associated with each other, as
      found in previous analyses of Caucasian populations (estimated haplotype
      frequency 5%). The Kozak rarer C variant was found at an allele frequency of
      9.1%, and appeared completely associated with the commonest haplotype of the
      other markers (VNTR/C, 145Thr). GPlb alpha genotype did not have any marked
      influence on pregnancy outcome. The Kozak/C variant was not significantly
      elevated in the 15 primigravidae patients who miscarried compared with 233 normal
      outcomes (OR=2.09, CI=0.7-6.4), neither was the 145Met variant (P =0.38). The
      Kozak/C variant was not elevated in the six primigravidae patients who developed
      pre-eclampsia (OR=0.84, CI=0.1-7.3). Comparison of the 271 primigravidae with 15
      recurrent fetal loss patients showed no association between Kozak/C and recurrent
      fetal loss (OR=0.65, CI=0.1-3.0), nor with the 145Met variant (OR=0.62, CI=0.1
      4.9). Combining miscarriage cases, recurrent thrombosis cases, pre-eclampsia, and
      intrauterine growth retardation outcome groups together, there is still no
      significant genotypic difference compared with normal outcome (OR=0.90, CI=0.4
      1.9). Genetic variants of GPlbalpha are unlikely to contribute to adverse events
      associated with thrombosis in a primigravidae population.

PMID- 15512547
TI  - Pregnancy outcomes in urban black South African women aged 35 years and older.
AB  - We measured maternal and fetal outcomes for black South African women of age 35
      years and above, compared with younger controls. The study was carried out at the
      Chris Hani Baragwanath Maternity Hospital and the Soweto Community Health
      Centres, that provide maternity services for urban black pregnant women. This was
      a retrospective pregnancy cohort, comparing pregnant women aged 35 and above with
      a control group aged 20-29 years. Early pregnancy losses (<20 weeks) were
      excluded. There were 1047 women in each arm of the study. Frequencies of
      hypertension (22.8%), gestational diabetes (0.9%), and prelabour rupture of the
      membranes (6.9%) were significantly higher for older women. Perinatal mortality
      rates (42/1000 vs. 33/1000) did not differ significantly. Antepartum admission,
      induction of labour, caesarean section and neonatal admission were required more
      frequently in older women. We conclude that pregnancy at age 35 years and above
      is often difficult and expensive, requiring hospital based interventions to
      maintain a low perinatal mortality rate.

PMID- 15512548
TI  - Low back pain, smoking and employment during pregnancy and after delivery - a 3
      month follow-up study.
AB  - Low back pain (LBP.), smoking and employment was studied among 111 consecutive
      women admitted to a maternity ward over a 6-week period, 40 were primiparas and
      71 multiparas. LBP was defined as any pain in the low back, irrespective of the
      specific cause of the pain. Two specially constructed questionnaires were
      utilised. The first was a, 14-item questionnaire which all participants answered
      before leaving the maternity ward. It included questions on employment and
      smoking and self-rating Visual Analogue Scales used for rating LBP. LBP was rated
      during the pregnancy and 3 days after delivery. The second questionnaire was used
      in a 90-day follow-up interview. The mean age of participants was 28 years. The
      prevalence of LBP during pregnancy was 58.5% among the 111 participants. Of the
      111, 75% continued to have LBP postpartum and at the 90-day post-delivery follow
      up, 54% of those with LBP during pregnancy were still experiencing LBP. Previous
      births and birth weight were not found to correlate positively with LBP. LBP
      during pregnancy did not affect the length of employment during pregnancy.
      Smokers had LBP more frequently during pregnancy and also after (P <0.002). It is
      concluded that smoking does seem to contribute to LBP during and after pregnancy.
      Birth weight does not affect LBP and LBP does not affect the length of employment
      during pregnancy.

PMID- 15512549
TI  - Review of shoulder dystocia at the Birmingham Women's Hospital.
AB  - A retrospective audit was performed of all deliveries between 1 January 1991 and
      31 December 1995 at the Birmingham Women's Hospital, the main University Teaching
      Hospital in the West Midlands. This was performed by using the computer database
      of all hospital deliveries, at the Women's Hospital during the above-mentioned
      period, by entering a CCL code for shoulder dystocia. During that period of time
      there were 28 932 deliveries with a mean caesarean section rate of 16.7%. One
      hundred and fifty-four cases were identified, of which 134 case notes were
      available for review. The incidence of shoulder dystocia was 0.53%. Audit was
      performed of pre-pregnancy, antepartum and intrapartum risk factors, the severity
      of shoulder dystocia, the category of person delivering the baby, fetal outcome
      at birth and subsequent pregnancy outcome in cases of those with subsequent
      pregnancies. Overall, the majority of cases of shoulder dystocia were mild, and
      dealt with by midwives (101 cases 74%). No severe cases were encountered, however
      three out of eight moderate cases delivered by obstetricians had evidence of
      fetal trauma (one Erbs palsy and two limb fractures). Twenty women had a
      pregnancy after the pregnancy complicated by shoulder dystocia. Of these, 18
      women delivered vaginally and there were two cases (10%) of repeat shoulder
      dystocia.

PMID- 15512550
TI  - How effective was the Health Education Authority's folic acid campaign?
AB  - The Health Education Authority's campaign, encouraging the use of
      periconceptional folic acid in the prevention of neural tube defects, started in
      February 1996 and is ongoing. Its effectiveness was assessed using a
      questionnaire, answered by patients not exposed to the campaign and by those that
      were. The study population was comprised of 337 women in approximately their 20th
      week of pregnancy, attending antenatal clinic for a routine fetal anatomy
      ultrasound scan. Data were collected on aspects of folate awareness, intake and
      sources of advice, before and after the campaign's start. Significant increases
      in preconceptional and total folate consumption, awareness of folate's benefits,
      and GP prescription were seen as the study went on. Unplanned pregnancy prevented
      compliance with periconceptional folate guidelines. We conclude that whilst the
      promotional campaign seemed to work in York, fortification of foodstuffs may need
      to be used to increase folate consumption in those with unplanned pregnancy.

PMID- 15512551
TI  - A Sitz bath does not improve wound healing after elective episiotomy.

PMID- 15512553
TI  - Reproductive outcome after abdominal myomectomy.
AB  - This is a retrospective study to evaluate the reproductive outcome after
      abdominal myomectomy. Seventy myomectomies were performed at the Jordan
      University Hospital over a 10-year period. Fifty-five percent of these patients
      were infertile at the time of surgery. The most common indication for the
      myomectomy was a combination of infertility and menorrhagia (34.2%). A successful
      pregnancy was recorded in 53.8% of those who attempted pregnancy after the
      operation.

PMID- 15512552
TI  - Management of women who are circumcised especially during pregnancy and
      childbirth.

PMID- 15512554
TI  - Emergency contraception: survey of knowledge, attitudes and practice of health
      care professionals in Ibadan, Nigeria.
AB  - This survey was conducted to determine the knowledge, and prescribing attitudes
      of emergency contraception among healthcare professionals in Ibadan, Nigeria. A
      questionnaire was administered to 735 health care professionals in selected
      healthcare facilities in Ibadan. These facilities were randomly selected as part
      of an ongoing programme designed to introduce emergency contraceptive pills
      (ECPs) as a clinic based method of family planning in service delivery outlets in
      the city. The response rate was 87.5%, comprising nurses (59.3%) and physicians
      (25.0%). Others were pharmacists, social workers and administrators. The results
      revealed that healthcare professionals' knowledge of various methods that can be
      used emergency contraception is very low. Less than half (35.1%) of the
      respondents were aware that combined oestrogen/progestin or progestin-only pills
      can be used as emergency contraception. Similarly, only 26.7% and 13.3% of the
      respondents were aware that intrauterine contraceptive devices and mifepristone
      respectively could be used as emergency contraception. While only 16.3% of the
      respondents had ever prescribed the combined pills as emergency contraception,
      10.9% and 8.2% had prescribed progestin-only pills and intrauterine contraceptive
      devices for this purpose in the past. Circumstances under which emergency
      contraception could be used vary among the respondents but 71.4% and 64.4% were
      of the opinion that condom breakage and sexual assault would be appropriate
      indications for its use. Two main sources, hospitals (68.4%) and pharmacies
      (8.8%) were identified by participants. It is apparent that one of the major
      barriers to frequent use of emergency contraception in Ibadan is the lack of
      awareness of its use by healthcare professionals. Therefore, there is an urgent
      need to educate these practitioners and include emergency contraception in the
      family planning curriculum of nursing and medical schools.

PMID- 15512555
TI  - Microinvasive cervical carcinoma: a retrospective study of cases presenting to
      the Oxford Colposcopy Unit between 1989 and 1996.
AB  - This a retrospective analysis of 65 cases of microinvasive disease and 5-8 years
      of follow-up (mean 6.2 years), evaluating the effectiveness of cytology and
      colposcopy in the diagnosis of microinvasive disease and the role of conservative
      surgery in its management. Cervical cytology reports indicated disease more
      severe than CIN III in 23% of cases. A further 7% at colposcopy were thought to
      have possible invasive disease despite no indication from the smear report, this
      impression correlated with increasing depth of invasion (>1.40 mm).

PMID- 15512556
TI  - Laparoscopic methotrexate treatment of ectopic pregnancy: feasibility, efficacy,
      safety and intrauterine pregnancy rates.
AB  - We set out to investigate efficacy, methotrexate (MTX) plasma concentrations, and
      toxicity following a single injection of MTX into the gestational site in the
      treatment of ectopic pregnancy. This was a non-randomised, non-blinded
      prospective clinical trial. Eighteen women with unruptured tubal pregnancies and
      in stable haemodynamic condition were studied. MTX 1 mg/kg was injected into the
      ectopic pregnancy guided by laparoscopy. Serum betahCG levels were estimated
      before MTX treatment and on days 1, 4 and 13. In 14 patients plasma MTX was
      determined 1 h and 6 h after the injection. We found an adequate decline in
      betahCG was achieved in 17 (94%) patients, and tubal surgery avoided in 15 (83%).
      At 6 hours following drug administration, mean plasma MTX concentration (0.36+/
      0.21 microM) was only 12% of mean peak level (3.1+/-1.0 microM). Six (39%)
      demonstrated slightly elevated, but completely reversible liver enzymes. None
      reported any subjective adverse effects. At the 4-7 year follow-up nine of 12
      (75%) women had delivered healthy babies. It is concluded that intratubal
      injection of 1 mg/kg MTX appears to be an effective and safe treatment of ectopic
      pregnancy.

PMID- 15512557
TI  - Gynaecology on the Net: evaluation of the information on hysterectomy contained
      in health-related web sites.
AB  - The popularity of the Internet is expanding rapidly and the number of patients
      accessing health-related web sites before a clinical consultation is increasing
      every day. Using popular Internet search engines we retrieved 26 health-related
      web sites containing patient information on hysterectomy. The web sites underwent
      a general evaluation on the base of principles of conduct suggested in the
      literature. The accuracy of the information was then compared with the one
      provided in the information leaflet produced by the Royal College of
      Obstetricians and Gynaecologists. There were only a few cases identified of
      misleading contents and, in general, the information was found to be accurate but
      rarely comprehensive. Poor adherence to some basic principles of conduct was also
      noticed.

PMID- 15512558
TI  - Vaginismus: results of treatment with botulin toxin.
AB  - In view of the long-term therapy necessary to cure vaginismus and specially
      persistent cases, we considered using botulin toxin (BT) injections for the
      treatment of such cases. Eight women (mean age 26.6 +/- 1.2 years) with
      vaginismus were treated with BT. Another five women with vaginismus, matching the
      eight patients in age, acted as controls. The patients in the study group were
      injected with BT (25 IU diluted in 1 ml saline) into each of the two
      bulbospongiosus muscles. Control patients were injected with saline. Mean follow
      up was 10.2 +/- 3.3 months. All the patients injected with BT improved. The
      couples could achieve satisfactory intromission. No patient was in need of re
      injection and there was no recurrence during the follow-up period. Control
      subjects did not improve with the saline injection into the bulbospongiosus
      muscle. In conclusion, BT injection effected cure in all of the vaginismus
      patients with no complications or recurrence. The technique is simple, easy, cost
      effective, not time-consuming and can be achieved on an outpatient basis.

PMID- 15512559
TI  - Vaginal dilator therapy-an outpatient gynaecological option in the management of
      dyspareunia.
AB  - The management of 18 women complaining of superficial dyspareunia is reviewed.
      Primary treatment consisted of self-vaginal dilatation using graduated glass
      dilators on an outpatient basis. All patients were given verbal explanation and
      written instructions. Treatment was considered successful with dilator therapy in
      14 (77.8%) women. Three (16.7%) women required additional therapy in the form of
      surgery or psychotherapy. We conclude that in selected cases, self-vaginal
      dilator usage on an outpatient basis is effective primary therapy for superficial
      dyspareunia.

PMID- 15512560
TI  - Does conventional HRT protect from urogenital atrophy? A prospective study.
AB  - Urogenital atrophy is a poorly defined entity. This prospective study looked at
      the effect of conventional HRT on urogenital atrophy. One hundred and sixty-three
      women were studied in a 12-month period. The incidence of urinary symptoms and
      clinical evidence of urogenital atrophy was found to be similar in both the 'HRT
      group' and the 'no HRT group'. This can be explained by the new oestrogen
      receptor theory. Conventional HRT does not seem to protect women from urogenital
      atrophy and receptor specific oestrogen therapy may be required to address the
      problem of urogenital atrophy and postmenopausal urinary symptoms.

PMID- 15512561
TI  - Pre-operative counselling-the patients' views.

PMID- 15512562
TI  - Struma ovarii presenting as hyperemesis gravidarum in pregnancy.

PMID- 15512563
TI  - Central serous retinopathy and severe preeclampsia.

PMID- 15512564
TI  - Antero-symphysial abscess formation after symphysial disruption in pregnancy.

PMID- 15512565
TI  - Hyperreactio luteinalis associated with normal singleton pregnancy.

PMID- 15512566
TI  - Acute haemorrhagic cystitis in pregnancy.

PMID- 15512567
TI  - Twin papyraceous fetuses in a triplet pregnancy.

PMID- 15512568
TI  - A rare twin pregnancy: a normal fetus and a complete hydatidiform mole.

PMID- 15512569
TI  - Hysterectomy in a woman with factor XI deficiency.

PMID- 15512570
TI  - Late ovarian metastases of a cutaneous malignant melanoma.

PMID- 15512571
TI  - A mesenteric recurrence of a granulosa cell tumour 35 years after first
      presentation.

PMID- 15512572
TI  - Uterus didelphys associated with left renal agenesis presenting as a pelvic
      kidney with contralateral ureteric obstruction.

PMID- 15512573
TI  - Retroperitoneal haematoma arising from vaginal myomectomy.

PMID- 15512574
TI  - An ectopic pregnancy in a previous caesarean section scar: treatment with
      systemic methotrexate and uterine artery embolisation.

PMID- 15512575
TI  - Carcinoma of the cervix presenting with post-defecation vaginal bleeding.

PMID- 15512576
TI  - Segmental resection of isthmic ectopic pregnancy with GIA: expensive spielerei or
      treatment of choice?

PMID- 15512577
TI  - Endometrioma in surgical scars.

PMID- 15512578
TI  - Shoulder dystocia: room for improvement?

PMID- 15512581
TI  - John William Ballantyne 1861-1923.

PMID- 15512582
TI  - Fetal fibronectin as a predictor of preterm birth.
AB  - Preterm delivery remains the leading cause of perinatal mortality and occurs in
      approximately 7-9% of pregnancies. The main problem for the obstetrician is the
      inability to detect women at risk from this complication. The presence of fetal
      fibronectin (fFN) in cervicovaginal secretions has been proposed as a specific
      predictor of preterm delivery. Immunohistochemical studies suggest that fFN is
      present in the extracellular matrix of the decidua basalis next to the
      intervillus space. It has been studied intensively in symptomatic patients and
      has a positive predictive value of 43-79%. It has also a negative predictive
      value of 99.7% for birth within 7 days and 93% for delivery before 37 weeks.
      Similarly, in high-risk asymptomatic women, it has been proved a useful screening
      tool for the prediction of preterm delivery, yielding a sensitivity of 43-92%, a
      specificity of 52-93%, a positive predictive value of 43-85% and a negative
      predictive value of 86-99%. In low-risk asymptomatic women, fFN has a sensitivity
      of 63-73%, a specificity of 80-98%, a positive predictive value of 13-36% and a
      negative predictive value of 95-97%. In women presenting with preterm
      contractions, a negative test may make one withhold potentially dangerous
      tocolytic therapy. In asymptomatic women this test can identify patients who have
      a very high risk for early delivery. Women identified as being high-risk can be
      offered steroid injections in order to improve lung maturity in preterm babies.
      Additionally, they can be counselled about the signs and symptoms of preterm
      labour, so that they can seek medical advice before labour is actually
      established. However, extensive research is still needed, as no clear benefit in
      preventing preterm birth using this test, has been shown so far.

PMID- 15512583
TI  - Medical risk factors in perinatal mortality in Kuwait: a case-controlled study
      from Al-Jahra district.
AB  - This study is the first of its kind in Kuwait. It evaluates various risk factors
      associated with perinatal mortality (PNM) in the Al-Jahra district hospital
      during the period January 1995-December 1997. Risks associated with PNM were age
      above 30, parity above 8, history of abortion or perinatal death, lack of
      antenatal care, presence of chronic maternal disease, hydramnios, antepartum
      haemorrhage, breech presentation and low Apgar scores. The effect of the
      appropriate preventative programmes involving highlighting women at risk of
      perinatal mortality and probable intervention are discussed.

PMID- 15512584
TI  - Risk factors for and perinatal mortality of abruptio placentae in patients
      hospitalised for early onset severe pre-eclampsia - a case controlled study.
AB  - We set out to determine which patients admitted for expectant management of early
      onset severe pre-eclampsia develop abruptio placentae and to compare the
      perinatal mortality rate of patients who developed abruptio placentae with those
      who did not have this complication. This was a case controlled study, using
      gestational age at delivery to select a control group for 69 patients who
      developed abruptio placentae. The only significant difference on admission was
      the higher uric acid levels in patients who developed abruptio placentae. Mean
      admission to delivery intervals were 11.9 and 8.8 days for the control and
      abruption groups respectively (P = 0.0083). Fifty-eight per cent of the babies in
      the abruptio placentae group developed late decelerations, as determined by fetal
      heart rate monitoring compared with 32% in the control group. Lactate
      dehydrogenase levels before delivery were significantly higher in the abruption
      group, but it only became elevated shortly before delivery and in the minority of
      cases. There were two intrauterine and four neonatal deaths in the abruption
      group and two neonatal deaths in the control group. Late decelerations detected
      by frequent fetal heart rate monitoring in patients with early onset severe pre
      eclampsia is the only early warning of abruptio placentae.

PMID- 15512586
TI  - Early teenage obstetrics at Waikato Hospital.
AB  - New Zealand has the second highest published teenage pregnancy rate in the world.
      Different papers have shown adverse obstetric outcome for teenage mothers. The
      aim of this study was to compare the obstetric parameters, such as birth weight,
      gestation at birth, Apgar scores, breech delivery, caesarean sections,
      instrumental deliveries, incidences of birth defects, twins, and gestational
      hypertension/pre-eclampsia of early teenage mothers with the rest of the
      population. The data were obtained from the perinatal information management
      system (PIMS) at Waikato Hospital for the period 1994 to 1996. The data were
      statistically analysed. There were 306 women in the early teenage group (17 years
      and younger) and 206 randomly selected women in the control group who were 18
      years or older. In the early teen group more than 92% of women were primiparous,
      whereas in the control group most women were multiparous. The analyses detected
      no differences in the two groups in the parameters studied except increased
      incidence of ventouse delivery in the early teenage group (P = 0.004). This was
      surprising because, older and parous women are supposed to have better outcomes.
      Hence there was no evidence from this study of any of obstetric risk factors
      associated with early teenage pregnancy. Also, race did not affect the means of
      birth weights, gestational age at birth and Apgar scores. Adjustment for race and
      parity differences did not change the conclusions apart from making the
      difference in incidence of ventouse delivery less significant (P = 0.067 when
      adjusted for parity differences).

PMID- 15512585
TI  - Long-term implications of caesarean section.
AB  - Previous reports have linked caesarean section with subsequent reduced fertility,
      increased rates of miscarriage/ectopic, time delay to next baby and lower fetal
      weight. However, most reports studied women delivering before 1980. The aim of
      this study was to assess whether these findings still apply. Five hundred and
      seventy-six primiparous women delivered by caesarean section during 1992-93 and
      576 controls were identified and followed for five years. No difference was
      observed for the time (months) to next pregnancy/delivery, proportion suffering
      miscarriage or ectopic or the number of subsequent children (P > 0.05, Mann
      Whitney U/chi-squared). Subgroup analysis by indication for caesarean section
      yielded similar results. Subsequent babies in the caesarean section group were
      statistically smaller and delivered earlier (median 3.4 kg/39 weeks, P <0.01,
      Mann-Whitney U) compared with the control group (median 3.5 kg/40 weeks). These
      differences are probably due to an increased rate of elective caesarean section
      in the caesarean section group. This study has largely refuted the findings of
      previous publications. Women delivered by caesarean section in the 1990s can be
      reassured that future fertility and miscarriage/ectopic risk will not be
      affected.

PMID- 15512587
TI  - Audit of anti-D immunoglobulin administration to pregnant Rhesus D negative women
      following sensitising events.
AB  - We performed a retrospective audit of 99 Rhesus D (RhD) negative women to
      discover if anti-D immunoglobulin (anti-D) prophylaxis was given in accordance
      with guidelines from the National Blood Transfusion Service Immunoglobulin
      Working Party (1991). It was found that all patients received appropriate
      management postpartum. However, more than half of the antepartum sensitising
      events beyond 20 weeks' gestation were not managed according to the guidelines.
      Only one patient was sensitised during the studied pregnancy and no sensitising
      events were recorded in her case. This supports the introduction of a policy of
      routine anti-D prophylaxis in the third trimester.

PMID- 15512588
TI  - Management of women who are Rhesus D negative in Northern Ireland.
AB  - In 1998, all 15 maternity hospitals in Northern Ireland participated in a
      retrospective survey of the management of pregnant women who were Rhesus D (RhD)
      negative. This area of clinical practice was chosen for study in the knowledge
      that a policy of routine antenatal prophylaxis had been proposed at the RCP/RCOG
      Consensus Conference, and that a change in current clinical practice was likely
      to follow. It was therefore felt prudent to survey critically current practice in
      order to collect baseline data before the introduction of new guidelines. Data
      were analysed on 3274 RhD negative women. The findings from this study show that
      current management of women who are RhD negative is suboptimal. In particular,
      there is poor adherence to the guidelines relating to the management of
      potentially sensitising events in pregnancy. Testing to assess the size of a feto
      maternal bleed was often omitted, and it was therefore impossible to ascertain
      whether an appropriate dose of anti-D immunoglobulin had been administered.
      Recent publications have also identified this as an area of concern. Trauma
      during pregnancy was often not managed appropriately, as a potentially
      sensitising event. Better compliance with the current guidelines was noted when
      management after delivery was considered. The reasons for this apparent
      inconsistency should be addressed. New guidelines, recommending the use of
      routine antenatal prophylaxis to all women who are RhD negative, have recently
      been published. Providers of antenatal care will need to address this issue
      within the context of their own practice environment. In doing so they should be
      mindful of current deficits in guideline compliance which may need to be
      remedied, to avoid building new practices upon fragile foundations.

PMID- 15512589
TI  - Unexpected rapid rise of maternal serum anti-D levels during pregnancy.
AB  - Two cases are described where hydrops faetalis developed as a result of very
      sudden and unexpected rises in serum anti-D levels. In both cases intravascular
      intrauterine transfusion was employed and a favourable outcome obtained. These
      cases show that continued vigilance is required even when anti-D levels are low.
      Weak antibody titres may be detected using enzyme-treated red cells, and failure
      to use this more sensitive technique meant that in one of the cases the initial
      weak antibody was not detected. There is currently a debate about the use of this
      more sensitive test in view of the increased work involved.

PMID- 15512590
TI  - An audit of trial of labour after previous caesarean section.
AB  - The first aim of the study was to assess the success rate of vaginal delivery
      after a trial of labour in women with history of caesarean delivery. The second,
      was to analyse the management used and suggest recommendations that might improve
      the outcome. The caesarean section rate in Tameside hospital, in the period of
      1995 and 1996, was (11%), 20% of which were repeat caesarean sections Fifty-one
      per cent of those with a history of previous caesarean section were allowed a
      trial of labour. The success rate of vaginal delivery in cases allowed trial of
      labour was 70%. But, if we include the 49% of cases who had elective repeat
      caesarean section in the calculation, the success rate for vaginal delivery would
      drop to 36%. More than one previous caesarean section was the main indication for
      elective repeat caesarean section. The second most common indication was
      cephalopelvic disproportion based on X-ray pelvimetry. Other indications included
      pregnancy-induced hypertension, breech presentation and maternal request. The
      main indication for repeat emergency caesarean section was fetal distress. Other
      causes included failure to progress, cephalo-pelvic disproportion, tender scar,
      ante-partum haemorhage and one case of ruptured uterus.

PMID- 15512591
TI  - Fetal growth and sex related to placenta praevia.
AB  - A retrospective study investigating all cases given a diagnosis of placenta
      praevia at the Birmingham Women's Hospital Trust, January 1993 to June 1997, was
      undertaken to investigate any neonatal sex or weight differences compared with
      the general singleton pregnancies. Mothers with placenta praevia were at
      increased risk of preterm delivery, fetal malpresentation and having a caesarean
      section as the mode of delivery. No differences were found in the fetal sex ratio
      or incidence of small for gestational age (SGA) infants and indeed male infants
      overall were larger for dates in the placenta praevia group when compared with
      their gestational equivalents in the control population. Although ultrasound
      assessment of pregnancies complicated by placenta praevia may be useful in
      checking the resolution of the condition by 'placental migration', there is no
      indication for its use in monitoring growth restriction.

PMID- 15512592
TI  - The value of ultrasound measurements in the Cameroonian child.
AB  - In this study we set out to establish the important ultrasonic measurement in
      Cameroonian foetuses and to compare the values with those obtained in European
      and North American patients. As we had anticipated, significant differences
      emerged. The values for biparietal diameter (B.P.D.) were substantially below
      those of Europeans, the difference widening with increasing gestational age until
      term. The femoral length was higher than European standards in the first and
      third trimester, but lower in the second trimester. The abdominal transverse
      diameter measurements were similar to those in European studies. We emphasise the
      importance of establishing local standards of ultrasonic growth patterns. Using
      European data may prove misleading.

PMID- 15512593
TI  - The effect of mode of delivery on neonatal outcome of twins with birthweight
      under 1500 grams.
AB  - The purpose of this retrospective study was to evaluate the mode of delivery on
      neonatal outcome of twins weighing <1500 grams. We reviewed the effect of birth
      order, presentation, and method of delivery on neonatal outcome in twin gestation
      under 1500 grams at Princess Badeea' Teaching Hospital in North Jordan over the 6
      years from 1994 to 1999. During the study period, there were 51 475 deliveries of
      which 695 were twin. One hundred and eight (108) sets of twins weighing <1500
      grams were included in the study (15.5%), of which 41 were in vertex-vertex
      presentation, 40 in vertex-nonvertex, and 27 with first twin in nonvertex
      presentation. The second twin was characterised by a higher incidence of
      respiratory distress syndrome (82% vs. 70%; P = 0.02), more neonatal mortality
      (23% vs. 17.6%), and lower Apgar scores at 1 and 5 minutes. Cesarean delivery for
      vertex-vertex presentation did not improve the neonatal outcome. Rather, the
      incidence of RDS was significantly greater in this group delivered by caesarean
      section (65.6% vs. 42%; P = 0.012). For nonvertex presentation, those delivered
      by caesarean section had a lower incidence of neonatal mortality. We conclude
      that there was no advantage in caesarean delivery after multivariate analysis to
      correct for differences in birthweight between the groups. The differences in the
      neonatal outcome of nonvertex twin presentation was accounted for by the
      differences in birthweight, rather than in mode of delivery.

PMID- 15512594
TI  - Caesarean section for the second twin after vaginal delivery of first.
AB  - Although caesarean section of a second twin after vaginal birth of the first twin
      is rare, it nevertheless has clinical importance as an acute emergency situation
      with high perinatal morbidity and mortality. We therefore found it appropriate to
      describe the obstetric management of such cases, including an overview of the
      literature and our own data. According to reports in the literature, 113
      deliveries of second twins (3.4%) were carried out by section in 3342 twin
      births. At our department in Tubingen there were 497 twin births (1.9%) in 26 095
      births. Of these the second twin was delivered by section in 11 cases (2.2%).
      This represents a statistical frequency of 0.04% of all births. As shown by case
      histories and our own study, the indications for abdominal delivery of the second
      twin were predominantly the prolapse of the umbilical cord or of small parts due
      to transverse or breech presentation, with simultaneous retraction of the cervix.
      Of our 11 births with emergency section, one child died postpartum. Because of
      above-mentioned risks the twin delivery must always be performed in a fully
      equipped facility, including facilities for intensive neonatal care.

PMID- 15512595
TI  - Practice observed: is speculum examination on admission a necessary procedure in
      the management of all cases of antepartum haemorrhage?
AB  - The objective of the study was to determine the justification or otherwise of
      admission speculum examination in women presenting with antepartum haemorrhage
      and the outcome/ benefits of the practice on women with antepartum haemorrhage
      presenting to the delivery suite of a UK teaching hospital. Factors studied
      included gestational age at presentation, associated factors with the bleeding,
      grade of medical/ midwifery staff performing the admission speculum examination,
      findings on speculum examination and ultrasound scan and the overall pregnancy
      outcome. Of the 564 (4.9%) women who presented with antepartum haemorrhage; 521
      had an admission speculum examination; 94.4% of these were by senior house
      officers (SHOs). The findings were a normal cervix (69%) and ectopy (21.3%). Of
      the women, 14.4% had recurrent bleeding and 8.5% went into preterm labour. The
      complications of the pregnancies, timing of delivery and management were
      independent of speculum examination. Admission speculum examination did not
      influence the management of pregnancies and the complications thereafter. These
      results suggest that such an intrusive procedure may not be justifiable in women
      presenting with antepartum haemorrhage.

PMID- 15512596
TI  - A review of the treatment failures following cervical intraepithelial neoplasia
      grade III treated by large loop excision of the transformation zone.
AB  - The records of 208 women were reviewed to quantify the long-term treatment
      failures of large loop excision of the transformation zone (LLETZ) in the
      treatment of cervical intraepithelial neoplasia (CIN) grade III. The rate of
      dyskariotic smears fell from 8% at 6 months to 2.3% at 48 months. The excision
      was considered incomplete in 84 cases (40.3%) of which 40 had endocervical
      margins involved. Thirty-five per cent of women with incomplete excision of CIN
      at the endocervical margin and 9% with complete excision had a dyskariotic smear
      within 4 years following LLETZ. These findings were statistically significant (P
      = 0.003 and 0.02 respectively). However, 5% only of women in the former group had
      cytological treatment failure at 6 months. There was no significant association
      between age and incidence of treatment failure. Further data are required to
      determine the risk of recurrence beyond 4 years before recommendations could be
      made about the duration of annual screening.

PMID- 15512597
TI  - The abnormal glandular smear: cytologic prediction, colposcopic correlation and
      clinical management.
AB  - We reviewed recent cytological reporting of abnormal glandular cells on cervical
      smears in order to assess the predictive value of these reports and the
      contribution of colposcopy in the assessment of these abnormalities. The study
      consisted of a 5-year retrospective review of the clinical management of 80 women
      with abnormal glandular cells on a cervical smear, with clinical and
      histopathological data available for review in the interval 1992-1996. There were
      two groups of women: (i) those referred with gynaecological symptoms and (ii)
      those with screen detected abnormalities who were asymptomatic and significantly
      younger than the first group. The predictive value of a glandular smear for
      malignancy was 42.5% and for premalignancy 28.8%. The most common lesions
      detected were cervical intraepithelial neoplasia (CIN) (13), endometrial cancer
      (13), cervical adenocarcinoma (10) and cervical intraepithelial glandular
      neoplasia (CIGN) (8). Four cases of endometrial carcinoma presented through
      screening. In the remainder a variety of benign conditions were identified as
      responsible for the abnormal smear. Failure to find an explanation for the
      abnormal smear only occurred in 8.8%. In developing a protocol for abnormal
      glandular smears, our observations indicate that: (a) those with abnormal
      bleeding require endometrial sampling; (b) for those with screen detected
      abnormality, colposcopy is valuable as it is a sensitive predictor of early
      invasion and can predict glandular abnormality; (c)diseases of the entire genital
      tract, non-gynaecological viscera and metastatic cancer can generate cytological
      abnormality; (d) screen detected borderline abnormality in endocervical cells is
      associated with CIN III.

PMID- 15512598
TI  - What are the factors associated with the follow-up preferences of women in long
      term remission from gynaecological cancer?
AB  - We set out to examine factors associated with follow up preferences of women
      attending routine hospital follow up after treatment for early stage
      gynaecological cancer. This was a retrospective cohort study, using hospital
      records and questionnaire data, and was based in North Staffordshire, UK. Fifty
      four women, who had undergone successful treatment for early stage gynaecological
      cancer and currently attending routine hospital follow up appointments, were
      studied. Follow-up preferences were established using a specially designed
      questionnaire. A questionnaire package containing psychological and demographic
      measures was used. Clinical details including site and stage of disease,
      treatment and follow-up type were obtained from medical records. There were no
      significant demographic or clinical differences between the women with preference
      for hospital follow-up and those women with a preference for discharge. Women
      with a preference for follow-up were found to have significantly higher anxiety
      (as measured by the MAC anxiety scale). These results were not found for the
      other anxiety scales (STAI and HADS). Three predictor variables (MAC anxiety,
      Education and Car ownership) were found to predict significantly group
      membership. It is not possible to predict follow-up needs using demographic,
      clinical or psychological factors. Follow-up needs are achieved through effective
      medical communication. The role of the specialist nurse is implicated. A larger
      scale study is necessary to elaborate this preliminary research.

PMID- 15512599
TI  - The value of interstitial thermotherapy as an adjunct to the treatment of uterine
      cervical leiomyomas.
AB  - Although cervical leiomyomas are rare, nevertheless, the proximity of the ureter
      and especially the uterine artery makes removal particularly hazardous. Six
      cervical leiomyomas were treated by interstitial thermotherapy to coagulate the
      entering blood vessels prior to excision. In no case was the ureter damaged and
      in none was there a problem with haemorrhage. This form of ancillary treatment
      is, therefore, commended.

PMID- 15512600
TI  - The outcome of pelvic examinations in women 40-60 years of age with lower urinary
      tract symptoms.
AB  - We set out to assess the outcome of pelvic examination in women 40-60 years of
      age with one or more lower urinary tract symptoms. This was an ongoing
      longitudinal cohort study set in one rural and one urban county in Denmark. One
      hundred and ninety-six women with one or more lower urinary tract symptoms
      occurring at least weekly were selected at random. Ages ranged from 40 to 60
      years. Pelvic findings involving genital prolapse, signs of vaginal atrophy, and
      pelvic mass as well as a history of hormonal status and estrogen deficiency
      symptoms were documented and assessed. One hundred and six women (54.1%) were
      recruited. First degree cystocele, rectocele, and uterine prolapse occurred in 24
      (22.6%), seven (6.6%), and six (5.7%), women respectively. No significant
      association between first-degree genital prolapse and subtypes of lower urinary
      tract symptoms (LUTS) was observed. The number of women with second or third
      degree cystocele, rectocele, and uterine prolapse was three (2.8%), two (1.9%),
      and two (1.9%), respectively. The positive predictive vaginal findings in each
      subtype of LUTS indicating an oestrogen deficiency were in the interval 72.0-
      90.0 while the negative predictive vaginal findings were in the interval 24.7
      27.6%, respectively. In six women (5.7%) a leiomyoma was observed. In one woman
      the size of the uterus exceeded the size of a 12-week pregnancy. Genital prolapse
      more than first degree and pelvic masses were infrequent findings among women
      with LUTS. Signs of vaginal atrophy associated poorly with a history of hormonal
      depletion and symptoms indicating oestrogen deficiency. However even an
      infrequent pathologic finding is significant. Therefore we still recommend pelvic
      examinations in all women with LUTS.

PMID- 15512601
TI  - Fertility after abdominal myomectomy.
AB  - This study aimed to evaluate the morbidity and pregnancy outcome of myomectomy in
      infertile women with uterine fibroids. This was a cross-sectional study. Records
      were reviewed for 100 consecutive women in the Rotunda Hospital who underwent
      myomectomy in the years 1995-1996. A questionnaire regarding subsequent fertility
      was sent. The study was carried out in the infertility unit at the Rotunda
      Hospital, Dublin, Ireland. Seventy-five women responded. Multiple myomectomy was
      performed in 52 (70%). Mean fibroid size was 6.8 cm (range 2-14.5 cm). Nine women
      (12%) developed complications; five had menstrual problems, two had wound
      discomfort and two had abdominal discomfort. Twenty-five women (33%) became
      pregnant. Seven (28%) were IVF pregnancies. Overall six (24%) miscarried. In 19
      of 25, pregnancy occurred where fibroids were the only identifiable cause of
      infertility. We conclude that abdominal myomectomy is associated with a
      favourable outcome in infertile women particularly if no other confounding
      variable is present.

PMID- 15512603
TI  - Acute puerperal uterine inversion: a report of five cases.

PMID- 15512604
TI  - Persistent hyperemesis gravidarum and Helicobacter pylori.

PMID- 15512602
TI  - Hysterectomy-the patient's view: a survey of outcomes of hysterectomy in a
      district general hospital.
AB  - Debate continues on the preferred method of hysterectomy, usually focusing on
      economic implications and details such as length of inpatient stay and time to
      return to work. However, little published data exists on patients' level of
      satisfaction with hysterectomy. We performed a retrospective survey of patients'
      views after different methods of hysterectomy. Patients were asked about
      discharge timing after operation, success or failure in relieving their symptoms,
      the presence of any new symptoms, and overall satisfaction. Six hundred and fifty
      three patients were identified. The questionnaire response rate was 82.5%. As
      noted by other authors there was a difference in the rate of return to normal
      activity, depending on the method of hysterectomy. Significantly a proportion of
      patients felt discharge was too early. There was no difference in overall
      satisfaction rates or in the incidence of new problems between methods. Overall,
      patients were highly satisfied with the outcome after hysterectomy with no method
      being superior.

PMID- 15512605
TI  - Teratoma or a twin? An unusual presentation of epignathus.

PMID- 15512606
TI  - A massive retroperitoneal cyst in pregnancy.

PMID- 15512607
TI  - Maternal goitre enlarging during labour as an indication for assisted vaginal
      delivery.

PMID- 15512608
TI  - Myocardial infarction in a woman with hypertrophic cardiomyopathy treated with
      beta-mimetics for premature labour.

PMID- 15512609
TI  - Rare skeletal injuries following true shoulder dystocia.

PMID- 15512611
TI  - A case of placenta increta presenting in the first trimester.

PMID- 15512610
TI  - Ischaemia of right colon complicating midtrimester pregnancy.

PMID- 15512612
TI  - An eclamptic episode in a low risk multiparous woman.

PMID- 15512613
TI  - Severe epithelial dysplasia of the fallopian tube: a potential source of
      malignancy arising from an often ignored organ.

PMID- 15512614
TI  - Recurrent high grade cervical intraepithelial neoplasia in a patient with
      cyclical neutropaenia: an analysis of HPV status.

PMID- 15512615
TI  - Incrustation of the thread of an intrauterine contraceptive device.

PMID- 15512616
TI  - Intravenous leiomyomatosis.

PMID- 15512617
TI  - A left inferior vena cava associated with pelvic vein malformations: a major
      pitfall of pelvic surgery.

PMID- 15512619
TI  - Coexistent extraovarian and bilateral ovarian dermoid cysts: a case presenting as
      an acute abdomen.

PMID- 15512618
TI  - An unusual mixed tumour of the uterine cervix.

PMID- 15512620
TI  - Postpartum spontaneous rupture of a benign cystic teratoma.

PMID- 15512623
TI  - Emergency obstetric hysterectomy-an increasing incidence.

PMID- 15512625
TI  - Management of diabetic pregnancies in the United Kingdom.
AB  - The aim of this postal questionnaire survey was to identify facilities currently
      available for the care of pregnant diabetic women in the United Kingdom and
      determine how closely these reflect the standards recommended by The St Vincent
      Declaration Action Programme. A questionnaire was sent to a physician and an
      obstetrician in each of the 255 obstetric hospitals in the UK. Two hundred and
      forty-five (96.1%) hospitals replied, with most of these managing 20 or less
      insulin dependent diabetics per year. Of the hospitals, 58.4%, had a special
      combined diabetic antenatal clinic; 86.6% of the units had a single physician
      responsible for diabetic care, whilst more than one obstetrician was involved in
      50.6% of the units. Prepregnancy counselling was provided in 87.4% of the
      hospitals. Home blood glucose monitoring was used in 97.9% of the units. Ideal
      mean pre- and postprandial blood glucose concentrations were 6.0 mmol/1 (SD 0.82)
      and 7.9 mmol/l (SD 0.91), respectively. Ultrasound was routinely used to assess
      fetal growth in 98.7% of the units. The mean gestational age for elective
      caesarean section was 38.2 weeks (SD 0.55), compared with 39.0 weeks (SD 0.35)
      for planned vaginal delivery. During labour, 98% of the units used a dextrose and
      insulin infusion, but only 53.7% of the units maintained an intrapartum maternal
      blood glucose of between 4 and 6 mmol/l. We conclude that there is widespread
      variation in the management of the pregnant diabetic patient, and much practice
      is suboptimal. Many of the recommendations of the St Vincent Declaration are not
      being met by current UK practice.

PMID- 15512626
TI  - Obstetricians' compliance with CDC guidelines on maternal screening and
      intrapartum prophylaxis for group B streptococcus.
AB  - How obstetricians' opinions regarding universal screening of pregnant woman for
      group B streptococcus and their attitude regarding chemoprophylaxis vary from the
      Centres for Disease Control (CDC) guidelines were studied, and the physician
      characteristics that predict divergent opinions were determined. Five hundred and
      eighty-two obstetricians in the Flanders region of Belgium were contacted by a
      postal survey. Ordinal logistic regression was used to assess obstetricians'
      characteristics that predict divergence. Only 44% agreed with routine prenatal
      screening for group B streptococcus of whom 72% would screen at 35 weeks.
      Intrapartum prophylaxis would be done on the basis of risk factors alone in 38%.
      Multivariate analysis revealed significant provincial differences (best in
      Antwerp, worst in West-Flanders) and increasing age was associated with
      decreasing compliance. It is concluded that a minority of the obstetricians
      believes in routine prenatal screening and one-third would give prophylaxis on
      the basis of risk factors alone. Obstetrician's age and province of practice
      predict divergent opinions.

PMID- 15512627
TI  - Is there a need for special antenatal clinic for women with a medical disorder?
AB  - A two year review of clinical practice in a medical antenatal clinic was
      performed. Forty-six per cent of the patients were diabetics and the other 54%
      were a mixture of endocrine, cardiac, vascular and other medical disorders. The
      referral rate was 1.5% of total deliveries during the time period and the
      perinatal mortality rate was 27/1000. The preterm delivery rate was 20%. The
      feasibility of this kind of clinic in a single hospital is discussed.

PMID- 15512628
TI  - Antioxidant levels in the cord blood of term fetus.
AB  - The aim of this study was to compare the differences in the total antioxidant
      levels in the cord blood after a normal vaginal delivery and after an elective
      caesarean section. This was a prospective study approved by the Wirral Hospital
      ethical research committee. The study was carried out in a district general
      hospital. We investigated 96 healthy pregnant women who had normal antenatal
      period with singleton pregnancies between 37 and 42 completed weeks of gestation.
      Sixty-five women had a spontaneous normal vaginal delivery and 31 underwent
      elective caesarean section. Umbilical cord blood was obtained immediately after
      delivery. Antioxidants such as glutathione peroxidase (GPX) and superoxide
      dismutase (SOD) were measured and compared between the normal vaginal delivery
      and elective ceasarean sections. The mean values for GPx in umbilical cord
      arterial blood (95; 86-103, n=74) was found to be significantly higher (P=0.0133)
      than that found in umbilical cord venous blood (84; 80-88, n=95). The arterial
      SOD values were found to be significantly higher (P=0.0337) in infants who had
      been delivered by caesarean section (1188; 1065-1311, n=22) than by vaginal
      delivery (1021;958-1083, n=39). The differences in the levels of GPX between the
      arterial and venous systems is not well documented but may be due to differences
      in the level of selenium, hydroperoxides or glutathione. In addition, why infants
      delivered by ceasarian section have a higher level of arterial SOD than those
      delivered by vaginal delivery remains unclear, but it may be a reflection of a
      relatively low level in infants subjected to the stress of labour.

PMID- 15512629
TI  - Pre-eclampsia - a problem of primipaternity not primigravidity?
AB  - Recent reports suggest that the incidence of pre-eclampsia may be associated with
      a change in paternity and the duration of cohabitation. In this study, we
      undertook to confirm the association between the duration of cohabitation and pre
      eclampsia by performing a case-control study. There was no significant difference
      between women with pre-eclampsia and their controls in respect to the duration of
      cohabitation.

PMID- 15512630
TI  - Antenatal detection of abnormal liver function tests - a marker for poor
      perinatal outcome.
AB  - The purpose of this study was to examine (a) the incidence of liver disease
      diagnosed in our antenatal population, (b) the diagnostic value of initial
      symptoms and liver function tests (LFTs), (c) the adequacy of investigation and
      management of the liver disorder and (d) the obstetric and neonatal outcome in
      this group of patients. Women with abnormal LFTs that delivered at our hospital
      over a 2-year period were identified from computerised hospital records and data
      was obtained from chart review. Forty-six out of a total of 13 181 (0.35%) women
      had liver disease diagnosed in pregnancy: Diagnoses included intrahepatic
      cholestasis of pregnancy (13), pre-eclampsia and the HELLP syndrome (eight),
      acute fatty liver of pregnancy (three), hyperemesis gravidarum (one), hepatitis C
      (13), B (four) and hepatitis A (one), cholelithiasis (two) and hepatitis of
      unknown aetiology (one). Symptoms at presentation were more predictive of the
      final diagnosis than the initial LFT profile. Investigation of the liver disorder
      was incomplete in 50% of cases. One mother required intensive care for 6 weeks
      postpartum and three others had significant postpartum haemorrhage. There was one
      neonatal death and 24 neonates were admitted to the special care baby unit.
      Eighteen women attended for their postnatal check up at 6 weeks. Eight of these
      women were referred to a hepatologist. Detection of liver disease in pregnancy
      identifies a group at risk of poor neonatal and maternal outcome. Structured
      guidelines should be implemented in obstetric units to facilitate appropriate
      investigation, treatment and referral patterns for these women.

PMID- 15512631
TI  - Prevalence and determinants of caesarean section in a teaching hospital of
      Pakistan.
AB  - A retrospective analysis of 10 863 caesarean sections was carried out at a
      teaching hospital in Pakistan to examine the factors responsible for the high
      caesarean section rate. The caesarean section rate (CSR) during the study period
      (1985-1996) was 24.1/100 births and 78% of the caesareans were emergency
      procedures. The caesarean section rate was significantly higher among
      primigravida (27.26%) compared with 22.31% in multipara (P<0.01). Even for each
      indication, the frequency of caesarean section was higher among prinigravida
      (P<0.05). The three leading indications were dystocia (6.32%), repeat section
      (5.8%) and fetal distress (3.5%). Specific socio-demographic and child bearing
      patterns of our women, flaws in antenatal surveillance, ineffective working of
      the referral chain and departmental polices regarding management of cases with
      dystocia, Previous, abdominal delivery and fetal distress seem to be the major
      underlying causes of the high CSR.

PMID- 15512632
TI  - Placenta praevia and scarred uterus - an obstetrician's dilemma.
AB  - Three cases are presented here of patients who had placenta praevia following a
      previous caesarean section. All three patients had placenta accreta and developed
      severe postpartum haemorrhage necessitating total abdominal hysterectomy. We
      highlight the importance of being aware of the probability of severe haemorrhage
      due to placenta accreta in patients with placenta praevia following a previous
      caesarean operation.

PMID- 15512633
TI  - Levels and risk factors of operative deliveries in four health facilities in
      Kisumu District, Kenya.
AB  - A prospective study was conducted in Kisumu district, a region characterised by a
      high incidence of maternal and infant mortality, to determine the levels and
      prevalence of maternal and perinatal complications and suggest ways to make
      maternal and child health programmes in the area more effective and practical.
      Four health facilities (two health centres and two hospitals) were selected to
      act as sentinel centres with two each representing urban and rural clusters. From
      these sentinel facilities, all the obstetric related cases were recorded between
      January and July 1997 and the outcome of the pregnancy was recorded. Some details
      about the respondents' socioeconomic, demographic, biomedical and environment
      characteristics were also recorded. A total of 1455 cases were recorded out of
      which 59% experienced obstetric-related complications whereas 41% had no
      noticeable complication. Of those with complications, 18% had a caesarean section
      and 6% had a ventouse delivery. Cross-tabulations and multivariate analysis have
      been conducted to identify the major risk factors for both caesarean and vacuum
      deliveries in the study area. Among other things, the study reveals that unbooked
      operative deliveries are common. Most women who undergo such deliveries are from
      poor socio-economic background, teenagers, single mothers and rural residents who
      may have past obstetric complications. Any meaningful policy measures aimed at
      managing and reducing incidence of surgical obstetric deliveries should seek to
      identify and address all these risk factors.

PMID- 15512634
TI  - Outcome of twin pregnancies in North Jordan.
AB  - In a retrospective study we examined the outcome of twins delivered at Princess
      Badee'a Teaching Hospital from 1 January 1996 to 30 June 1999. The incidence of
      twin pregnancy was 1/86 with a gross perinatal mortality rate of 178 per 1000.
      Breech presentation was associated with the highest perinatal mortality rate (278
      per 1000). One hundred and eighty-four out of the 386 twin pregnancies were
      preterm with the highest perinatal mortality rate (184 per 1000). The neonatal
      Mortality rate fell with increasing birthweight from 532 per 1000 at 1500 g to 16
      per 1000 at 2500 g. Our results showed that the risk factors were mainly
      prematurity, low birthweight, pregnancy-induced hypertension, lack of proper
      antenatal care, birth asphyxia, and malpresentation.

PMID- 15512635
TI  - Conservative management of ovarian cysts in pregnancy during third trimester and
      intrapartum.
AB  - We treated two patients with large ovarian cysts in pregnancy conservatively. In
      both cases, aspiration of the cysts under ultrasound guidance allowed successful
      vaginal delivery. In one case, the cyst fluid reaccumulated, and required further
      aspiration in labour. In both cases, benign ovarian cysts were removed
      laparoscopically at a later date. Various strategies for dealing with ovarian
      cysts in pregnancy are discussed.

PMID- 15512636
TI  - Vaginal malignancies in childhood and adolescence.
AB  - Throughout the years 1978-1998, 13 patients, 9 months to 16 years of age, were
      treated for vaginal malignancy at the Medical City Hospital, Baghdad, Iraq. The
      majority were found to have an embryonal sarcoma, an endodermal sinus tumour or a
      clear cell adenocarcinoma. Most were treated by genital resection combined with
      triple cytotoxic therapy. We have eight survivors for more than 3 years following
      surgery. This study also illustrates the potential curability of these tumours
      with preservation of urinary function.

PMID- 15512637
TI  - Differential efficacy of gonadotropin-releasing hormone (GnRH) agonist treatment
      on pedunculated and degenerated myomas: a retrospective study of 630 women.
AB  - This study was designed to compare the anatomical location of myomas (submucous,
      intramural, subserous, or cervical), whether pedunculated or non-pedunculated if
      degenerated or undegenerated and relating these findings to myoma volume
      reduction in women treated with gonadotropin-releasing hormone agonist (GnRHa).
      Our retrospective study group included 630 patients with symptoms attributed to
      fibroids. They were treated with a single GnRH agonist for 20 weeks and the size
      of the myoma was monitored by magnetic resonance imaging and/or ultrasonographic
      scan. During a 20 week-treatment, submucous, intramural, or subserous fibroids
      showed an overall reduction of 63% (P<0.01) with little variation between these
      types. No reduction in size was seen in cases of pedunculated, degenerated, or
      cervical myomas. These data suggest that GnRH agonist therapy might be used
      primarily for non-pedunculated and undegenerated myomas.

PMID- 15512638
TI  - Sexual behaviour and negotiation of the male condom by female students of the
      University of Ibadan, Nigeria.
AB  - This study explored the sexual behaviour of unmarried female students of the
      University of Ibadan, Nigeria, and assessed the extent to which those who were
      sexually active negotiated and used the male condom. Four focus group discussions
      were conducted followed by a survey of 354 students. The results show that the
      mean age of the students was 22.5 years 55.1% had had sexual intercourse; the
      mean age at first intercourse was 16.5 years. The number of lifetime sexual
      partners ranged from 1 to 20 with a mean of 3.4; 75% of those who had had sex
      reported ever using condom; 16.9% and 39% used it during their first and last
      sexual episodes respectively; only 34.3% used it consistently. Seventy-three per
      cent had ever negotiated condom use with a partner, but only 41% did so during
      their last sexual encounter. A significant association was found between condom
      negotiation and number of sexual partners: Students with fewer life time partners
      (3.2) had less frequently negotiated condom use than those with more partners
      (4.3) (P<0.05). Condom negotiators also scored significantly higher (4.6) on a 6
      point AIDS Knowledge Score than those who had never done so (4.0) (P<0.05). About
      a quarter (26.7%) had ever bought a condom, while 38.5% had ever carried it. We
      conclude that although many female students had sometimes used a condom only a
      few used it consistently and are therefore at risk of the unintended outcomes of
      unprotected sex. We propose appropriate interventions to address the problem.

PMID- 15512639
TI  - An audit of conservative surgery for endometriosis in a district general hospital
      1995-1998.
AB  - As conservative surgery for endometriosis is a relatively new introduction to our
      hospital we felt it would be of value to audit our results and compare these with
      results from published series. We sent postal questionnaires to 104 patients who
      had undergone surgery over the past 3 years to assess their response to
      treatment. We combined this with an additional questionnaire to patients who had
      a Laparoscopic uterine nerve ablation (LUNA) procedure. We received replies from
      81% of the patients with 81% having symptom improvement following their
      operation. Eighty-seven per cent of patients who had LUNA returned the
      questionnaire with 64% having some symptom improvement following surgery. On the
      basis of our results we will continue to offer conservative surgery for
      endometriosis as the best primary treatment but have some reservations about the
      addition of LUNA in patients with endometriosis.

PMID- 15512640
TI  - Transcervical resection of endometrium: patient satisfaction survey at a district
      general hospital.
AB  - A postal survey of transcervical endometrial resection in a series of 370
      consecutive patients, treated at Ipswich District General Hospital between 1991
      and 1997, is presented. All patients had total transcervical endometrial
      resection (TCER) procedures. Of our patients,258 (69.7%) reported a significant
      improvement in menstruation. Of the patients, 113 (21.9%) became amenorrhoeic. In
      all, 81 (21.9%) hysterectomies were performed. On direct questioning, 262 (70.8%)
      answered that they were satisfied with the outcome. It is concluded that our
      postal survey consolidates the previous findings that transcervical endometrial
      resection is a safe and effective operation with a high satisfaction rate even at
      a district general hospital setting. It should compliment medical treatments and
      hysterectomy in the management of women with menorrhagia.

PMID- 15512641
TI  - The prevalence and practice of female genital mutilation in Nnewi, Nigeria: the
      impact of female education.
AB  - Three hundred and twenty-five consecutive live female deliveries at Nnamdi
      Azikiwe University Teaching Hospital, Nnewi were followed up for 9 months for
      evidence of any genital mutilation. Their mothers were examined for genital
      mutilation and a questionnaire based on face-to-face interview of the mothers was
      also administered. There was no genital mutilation observed among the 200 female
      babies whose mothers completed the 9 months follow up, The prevalence of genital
      mutilation among the mothers was 48%. The prevalence of female genital mutilation
      among the mothers increased with age. The circumcision index C.I. was zero and
      3.0 at 16-20 years and 31-35 years age groups, respectively. Also the prevalence
      decreased with increasing level of education. The circumcision index was 1.0 for
      mothers at primary level education and least 0.33 at tertiary level of education.
      There was no relationship with parity. None of the mothers was willing to allow
      genital mutilation to be performed on her baby but 36% applied local treatment to
      the clitoris especially powder (28%). Dystocia was the commonest complication in
      the mothers and the knowledge about female genital mutilation was acquired
      informally from fellow women. Female education is paramount in the campaign and
      advocacy against female genital mutilation.

PMID- 15512642
TI  - Vaginal excision of cervical stump.
AB  - If the cervix, left behind at subtotal hysterectomy, requires removal, the
      vaginal route is probably the safest, and least traumatic. Abdominal dissection
      is often difficult and a laparoscopic approach is hazardous as the anatomical
      landmarks are not clear. Five cases are described, to illustrate the surgical
      technique. As there is an increase in subtotal hysterectomy in some centres,
      removal of the residual cervix may be required more frequently.

PMID- 15512643
TI  - Perceptions and attitudes of Nigerian women about the menopause.
AB  - The attitudes of women to the menopause are strongly influenced by social,
      cultural and economic settings in which they live and may also reflect the
      differences in modes of treatment for or perception of its symptoms. The object
      of this study was to determine the perception and attitude of post-menopausal
      Nigerian women to the menopause. We interviewed 676 women who had experienced at
      least 24 months of amenorrhoea using a structured questionnaire. Menopause was
      considered a normal physiological manifestation of the ageing process by 95.56%
      of the respondents while 2.66% believed it was a disease condition. The majority
      of the women had a positive attitude to the menopause and indicated that it did
      not affect their relationships with their spouses or children. For most of the
      women (71.13%), sexual life ended with menopause. None of the women was on
      hormone replacement therapy but among those sexually active, reduced
      libido/frequency and vaginal dryness were reported by 24.59%. The most commonly
      reported advantage of menopause was freedom from cyclical bleeding. We conclude
      that although Nigerian post-menopausal women have a positive disposition towards
      menopause, they may have a significant reproductive health burden which has been
      tolerated for so long. It is important to determine the influence of
      sociocultural belief on sexuality after menopause and also evaluate the benefits
      of hormone replacement therapy in our environment.

PMID- 15512644
TI  - Constipation, faecal incontinence and urinary symptoms in women awaiting
      hysterectomy.

PMID- 15512645
TI  - Imaging and torsion of ovarian tumours.

PMID- 15512646
TI  - Guillain-Barre disease in pregnancy treated with intravenous immunoglobulin.

PMID- 15512647
TI  - Purpura fulminans in the early postnatal period in a woman with protein C
      deficiency.

PMID- 15512648
TI  - Medical management of second trimester fetal death complicated by a complete
      placenta praevia.

PMID- 15512650
TI  - Maternal ketoacidosis complicating acute starvation in pregnancy.

PMID- 15512651
TI  - Transient isolated fetal ascites and intravenous ritodrine therapy: a possible
      association.

PMID- 15512649
TI  - Marfan's syndrome and myasthenia gravis in pregnancy.

PMID- 15512652
TI  - Review of the diagnosis and transmission of thanatophoric dysplasia and report of
      a familial case with three affected siblings.

PMID- 15512653
TI  - Spontaneous antepartum uterine artery rupture.

PMID- 15512654
TI  - An advanced primary ovarian pregnancy.

PMID- 15512655
TI  - Tuberculosis, the great mimic again? A report of two cases of pelvic tuberculosis
      initially suspected to be advanced ovarian carcinoma.

PMID- 15512656
TI  - A fatal methotrexate-treated case of ectopic pregnancy with genital tuberculosis.

PMID- 15512657
TI  - A true hermaphrodite case with 46, XY/46, XX karyotype.

PMID- 15512658
TI  - Catamenial pneumothorax.

PMID- 15512659
TI  - Pelvic actinomycosis mimicking frozen pelvis: report of an unusual case.

PMID- 15512660
TI  - Benign cystic peritoneal mesothelioma.

PMID- 15512661
TI  - Localised endometrial cancer presenting with massive ascites.

PMID- 15512662
TI  - Management of placenta praevia.

PMID- 15512666
TI  - Interstitial cystitis.

PMID- 15512667
TI  - Risks for obstetricians - a review of the current issues and literature.

PMID- 15512668
TI  - Shoulder dystocia.

PMID- 15512669
TI  - Improving the standards of care for women having caesarean sections.
AB  - Improvement in the uptake of prophylactic antibiotics at caesarean section was
      chosen as a priority at the 1994 ASQUAM (Achieving Sustainable Quality in
      Maternity) meeting. The interventions used were guidelines, cyclical audit of
      cases and a patient-specific reminder stamp in the notes. A more detailed
      qualitative assessment of standards of communication and outcome was undertaken
      on a smaller cohort of women. Data on antibiotic prophylaxis were obtained from
      an audit record completed for every caesarean section undertaken at North
      Staffordshire Hospital from 1996 to 1998. Information on morbidity following
      caesarean section and on counselling was obtained from a review of the case
      records of a consecutive series of 75 caesarean sections and from a telephone
      call. In the baseline audit, 75% of women had received antibiotics; this
      increased to 92% in the remainder of 1996, 95% in 1997 and 98% in 1998. Fifty
      eight of the 75 women were contactable by telephone (77%); of these 16 (28%) had
      a 'wound infection', 12 of which developed after discharge from hospital. Only 25
      women (43%) remembered being counselled about the caesarean section. It is
      possible to achieve significant improvements in the quality of care for women
      having caesarean sections through the use of local guidelines, cyclical audit and
      reminder stamps. However, this audit, with community follow-up, raises questions
      about the adequacy of single dose prophylaxis. It also suggests the need for
      improved compliance with RCOG communication following caesarean section
      guidelines.

PMID- 15512670
TI  - Maternal and neonatal seroprevalence of human immunodeficiency virus antibodies
      in Benin City, Nigeria.
AB  - The prevalence of human immunodeficiency virus antibodies in mothers and their
      neonates was determined through unlinked anonymous HIV testing at delivery. Two
      hundred and forty-six apparently healthy volunteer anonymous parturients at the
      University of Benin Teaching Hospital, Nigeria, and their neonates were recruited
      for the study. Blood samples were collected from the mothers and cord blood from
      their neonates at delivery. The blood samples were coded and assayed for HIV
      antibodies using ImmunoComb HIV 1 and 2 bispot test and ImmunoComb II HIV-1 and 2
      CombFirm, both from PBS Orgenics, France. The results for maternal and neonatal
      blood sample pairs were matched. The maternal seroprevalence for HIV antibodies
      was 2.4% (6/246) while only two infants had HIV antibodies. The mother-to-child
      transmission of HIV antibodies was 33.3%. The study highlights the increasing HIV
      infection among pregnant women in this hospital. The risk of vertical
      transmission is therefore high. Universal antenatal HIV testing with an opt-out
      system is suggested. The need for our maternity centres and special care baby
      units to establish management protocols and anti-retroviral therapy for HIV
      infected women and their neonates is recommended.

PMID- 15512671
TI  - Trends in obstetric care in the United Kingdom.
AB  - This is a comparative study of the annual statistical returns to the Royal
      College of Obstetricians and Gynaecologists for 1993, 1994 and 1997/8. Over the
      study period there has been a decrease in normal vaginal deliveries of the order
      of 3% which is mirrored by a similar increase in caesarean section rates.
      Induction of labour rates have remained relatively constant 22.22%, 22.96% and
      24.79% for 1993, 1994 and 1997/8, respectively. The overall instrumental delivery
      rate has changed little but there is an increasing preference for vacuum
      extraction over forceps. Analysis of the figures for each country (England,
      Scotland, Wales and Northern Ireland) show broadly similar trends.

PMID- 15512672
TI  - Urinary output during induced labour in normotensive women: a prospective pilot
      study.
AB  - All fluid intake and urine output were monitored and measured in 103 consecutive
      women with normal blood pressure and without a history of pre-existing renal
      disease during induced labour for various indications. Epidural analgesia was
      administered in all these women and labour was augmented with oxytocin infusion.
      All urine specimens passed were tested for specific gravity. The temperature of
      the labour rooms was between 25 and 27 degrees C. Analysed results (from 50
      women) shows that at a mean fluid intake of 75 ml/hour (standard deviation (SD)
      21.84), oliguria (urine output <30 ml/hour) occurred in 42 (84%) of the women.
      There was a positive correlation between fluid intake and urinary output
      (r(2)=0.8515, P<0.0001). Urinary specific gravity was high (>1010) in all the
      specimens throughout the study. This study suggests that oliguria may be a common
      component of labour managed in this manner and its interpretation in pre
      eclamptics in labour may be viewed in this context. Oliguria may therefore be a
      poor indicator of renal function or worsening pre-eclampsia during labour and its
      management needs to be limited to the severe and persistent variety to avoid
      renal complications. We believe from this study that relevant urine and blood
      biochemistry are better correlates of renal function in labour.

PMID- 15512673
TI  - Maternal and perinatal outcome with drug abuse in pregnancy.
AB  - This study was undertaken to evaluate the maternal and neonatal outcome in women
      abusing drugs. A retrospective case-control study was conducted on 35 drug
      abusers who delivered between January 1994 and August 1997 at Birch Hill
      Hospital, Rochdale. Heroin was the most commonly used drug. The major antenatal
      complications were anaemia (37%). IUGR (25.7%), prematurity (14.2%) and abruptio
      placenta (8.5%). Neonatal outcome with regard to birth weight, head circumference
      and body length did not show any significant difference between the study and
      control group. There was one stillbirth, giving a perinatal mortality rate of
      28.5/1000 total births.

PMID- 15512674
TI  - Measurements of anterior fontanelle during the fetal period.
AB  - In this study, we aimed to determine the development of the anterior fontanelle
      during the fetal period by morphometric measurements. One hundred and five (49
      males, 56 females) human fetuses were obtained from Isparta Maternity and
      Pediatric Hospital. The gestational age ranged from 11 to 40 weeks. In all cases,
      head circumference, head length and biparietal diameter were recorded. The
      anterior fontanelle, transverse and longitudinal diameters were measured, and the
      mean anterior fontanelle size and the anterior fontanelle area were calculated. A
      significant positive correlation was found between the gestational age and all
      parameters. During the fetal period, the anterior fontanelle area gradually
      increased with head circumference. There was a sharp increase in third trimester
      in the area anterior fontanelle. In the present study, there was no significant
      difference between sexes regarding the all parameters measured or calculated. The
      mean anterior fontanelle size was larger than that recorded in previous studies
      for both sexes. As presented in our study, the dimensions of the anterior
      fontanelle for each gestational age will be useful in the understanding of
      development and anatomical variation. It may also be useful in the diagnosis of
      cranial maldevelopment.

PMID- 15512675
TI  - The effect of maternal exercise on umbilical artery blood flow in insulin
      dependent diabetics.
AB  - Nine insulin-dependent diabetic women underwent a moderate exercise test. The
      mean exercise intensity achieved was 65% (50-80%) of submaximal exercise. The
      maternal heart rate rose significantly after exercise from a mean of 85 b.p.m.
      (60-109 b.p.m.) to a mean of 140 b.p.m. (112-168 b.p.m.). Maternal systolic blood
      pressure rose significantly from a mean of 115 mmHg (90-130 mmHg) to a mean of
      157 mmHg (145-180 mmHg). The diastolic blood pressure also rose, but
      insignificantly, from a mean of 71 mmHg (65-90) mmHg to a mean of 85 mmHg (80-90)
      mmHg after exercise. The mean umbilical pulsatility index (PI) showed significant
      decrease at 2 and 6 minutes of recovery from exercise and subsequently showed a
      significant rise after 20 minutes. This rise continued even after a full 30
      minutes of recovery from exercise.

PMID- 15512676
TI  - Efficacy of haptoglobin administration in the early postoperative course of
      patients with a diagnosis of HELLP syndrome.

PMID- 15512677
TI  - Burst abdomen following caesarean section: a preventable surgical complication.

PMID- 15512678
TI  - Is osteitis pubis associated with the use of bone anchors in urinary continence
      operations?
AB  - We studied 130 patients who underwent either a vaginal needle suspension
      procedure or a pubofascial sling procedure with Mitek titanium bone anchors to
      determine the association of osteitis pubis with bone anchoring in these
      procedures. Fifteen patients complained of postoperative suprapubic pain; five
      cases were due to wound infections and another five were associated with tying
      the suspension sutures too tightly. We suggest the use of the term 'periostitis
      pubis' to describe the remaining five patients who suffered suprapubic pain. We
      found no radiological evidence of osteitis pubis in any patients.

PMID- 15512679
TI  - Induced abortion: a four-year experience at a University Gynaecological Clinic in
      Greece.
AB  - The aim of this study was to estimate the percentage of women who asked for
      pregnancy termination as an alternative to using family planning. The reasons
      given for requesting termination were documented and evaluated. During a 4-year
      period, 663 women came to the Family Planning Department. Four hundred and ninety
      one (77.6%) were pregnant, in the first trimester of pregnancy and requesting an
      induced abortion. Consultation and counselling resulted in a 25% decrease in the
      number who finally had their pregnancies terminated. The low socio-economic
      status of most of the women and the negative attitude of our society towards an
      unmarried mother remain the main reasons for a high rate of therapeutic abortion.

PMID- 15512680
TI  - Laparoscopic surgical management of ectopic pregnancy: a district general
      hospital experience.
AB  - This is an audit of laparoscopic management of ectopic pregnancy in a District
      General Hospital (DGH), using a retrospective casenote review. The study was
      conducted at New Cross Hospital, Wolverhampton, a large DGH. We recorded the
      duration of operation, postoperative opiate requirement, length of hospital stay,
      operative and postoperative complications. Case notes of patients with surgically
      treated ectopic pregnancies between January 1996 and June 1998 (n=106) were
      reviewed and grouped into three categories: (1) immediate laparotomy, (2)
      laparoscopy followed by laparotomy, and (3) laparoscopic management. Comparisons
      were made between the three groups. The incidence of ectopic pregnancy was 1-91
      live births. The mean age of the patients was 29.9 years (range 14-41). Seven
      (6.6%) patients were haemodynamically unstable and underwent immediate
      laparotomy, 66 (62%) patients had laparoscopic management while 33 (31%) patients
      had laparotomy following preliminary laparoscopy. Mean operative time in the
      laparoscopic management group was 61.9 minutes. The mean +/- 2 SD was 61.9+/-37.4
      (range 27-107) with a mean length of hospital stay of 1.9 days (range 1-4),
      compared with 49.9 minutes (+/-SD 16.5 (range 35-98) and 3.9 days (range 2-8),
      respectively, in the laparotomy following preliminary laparoscopy group. Only one
      patient in the laparoscopic management group required opiate analgesia 24 hours
      postoperatively compared with all the patients in the immediate laparotomy group
      and seven patients (21%) in laparotomy following the preliminary laparoscopy
      group. Complications in the laparoscopic management group included wound
      infection and a persistent ectopic. One patient in the laparotomy group required
      subtotal hysterectomy for persistent bleeding from cornual ectopic, while
      complications in the laparotomy following the laparoscopy group consisted of
      minor wound infection and a case of deep venous thrombosis (DVT). Laparoscopic
      management of ectopic pregnancy is safe and can be carried out successfully in a
      DGH setting with clear advantages, including shorter hospital stay and reduced
      postoperative opiate requirement.

PMID- 15512681
TI  - Advanced cervical carcinoma in Ibadan, Nigeria: an appraisal of radiation
      therapy.
AB  - This is a retrospective study of 500 patients with advanced cervical cancer (FIGO
      Stages IIB, III and IVA) who were seen and managed at the University College
      Hospital Ibadan between 1988 and 1992. External pelvic radiation therapy plus
      intractivary radioactive caesium brachytherapy was mainstay of treatment.
      Complete response to therapy was recorded in 68% of patients with stage IIB, 57%
      in stage III and 41.2% of patients in stage IVA. In patients with stage IIB, the
      local tumour control was 65%, in stage III patients 54% and in patients with
      stage IV 41%. The cumulative rates of survival at 5 years (for all the patients
      with stage IIB, III and IVa) were 41.5%. The cumulative rates for disease-free
      survival at 5 years was 25.5%. Radiotherapy as the sole treatment modality in the
      management of advanced cervical cancer in Ibadan has yielded poor results as
      revealed in this study. There is an urgent need to evolve a new treatment policy
      with the aim of improving the response rate and survival in this group of
      patients.

PMID- 15512682
TI  - Does leaning forward improve micturition?

PMID- 15512683
TI  - Treatment of menorrhagia with the levonorgestrel intrauterine system: can we
      learn from our failures?

PMID- 15512684
TI  - Extralobar pulmonary sequestration with contralateral pleural effusion.

PMID- 15512685
TI  - Vesicovaginal fistula occurring 48 hours after insertion of a ring pessary.

PMID- 15512686
TI  - The value of GnRHa in an IUI treatment programme.

PMID- 15512716
TI  - Guidelines on nutrition.

PMID- 15512717
TI  - Stillbirth: a review.
AB  - Stillbirth occurs in nearly 1% of all births in the USA, and is one of the most
      common but least studied adverse pregnancy outcomes. The many risk factors for
      and causes of stillbirth are presented. Over the past several decades, the rate
      of stillbirth has been substantially reduced, with the reduction most apparent in
      those stillbirths previously occurring at term and/or in labor. Reductions have
      occurred because of reductions in risk factors (i.e. prevention of Rh disease and
      better control of diabetes), better antepartum monitoring of those with risk
      factors followed by early delivery for those fetuses found to be at risk (i.e.
      growth restriction, maternal pre-eclampsia), better intrapartum fetal monitoring,
      increases in Cesarean section for those at risk, and early detection of
      congenital anomalies followed by termination prior to the time that these early
      fetal deaths are classified as stillbirths. Finally, the value of using fetal
      autopsy and placental examination to determine the cause of death accurately,
      both for research purposes and for patient counseling in future pregnancies, is
      explored.

PMID- 15512718
TI  - The progression of disease stage in twin-twin transfusion syndrome.
AB  - OBJECTIVE: To estimate the frequency of progression or regression of disease
      stage in pregnancies complicated by twin-twin transfusion syndrome (TTTS) managed
      with non-placental laser techniques. METHODS: A cohort of TTTS pregnancies within
      the sole perinatal center for the state of Western Australia was examined. All
      cases of prenatally identified TTTS from 1992 to 2002 were staged at diagnosis
      (retrospectively prior to 2000, prospectively since). Amnioreduction and
      septostomy were the principal therapies used. Features associated with
      progression, regression or stability were identified. RESULTS: During the study
      period, 71 cases of TTTS were managed. Amnioreduction was performed in 73.2%,
      with no difference in the median number of procedures by stage (p = 0.178). In
      21.1% of cases, TTTS resolved completely with persistent normalization of
      amniotic fluid volumes after amnioreduction (median number of procedures: 2).
      Disease resolution was associated with pregnancy prolongation, greater
      gestational age at delivery (36 weeks vs. 28.4 weeks, p < 0.001) and increased
      perinatal survival (100% vs. 42.6%, p < 0.001) compared with stage progression.
      Logistic regression analysis predicted that the probability of both infants
      surviving was 80% if the pregnancy remained at Stage I or II throughout, compared
      with a probability of 50% if it reached Stage III or more at 26 weeks, and only
      25% if the disease reached Stage III or more at 16 weeks' gestation. CONCLUSION:
      Pregnancy outcome for TTTS managed with amnioreduction techniques is correlated
      with stage at diagnosis and the subsequent disease evolution. However, the
      progression of stage in TTTS is unpredictable and the likelihood of spontaneous
      fetal demise was not different between stages.

PMID- 15512719
TI  - Frequency of nursing, physician and hospital interventions in women at risk for
      preterm delivery.
AB  - OBJECTIVE: To determine the frequency of nursing intervention, physician
      treatment and hospital evaluation for women receiving outpatient management
      services for preterm labor. METHODS: Outpatient services included: patient
      education; daily and as-needed nursing assessment of monitored uterine activity
      (MUA) and patient symptoms; treatment compliance; and physician notification for
      values exceeding established limits. We analyzed service data from women with
      singleton gestations at 20.0-34.9 weeks. RESULTS: Overall, 307 249 days of data
      from 10 660 women were reviewed, and 634 983 hours of MUA was assessed. On 53 665
      (17.5%) of monitored days, patients exhibited increased MUA and/or symptoms of
      preterm labor with nursing intervention and reassessment. Physician
      notification/intervention was required 7316 (13.6%) times, and hospital admission
      was needed for 3163 (43.2%) of these patients. In the hospital 1400 (44.3%)
      patients received tocolysis. The mean ( +/- standard deviation) length of
      hospital stay was 3.2 +/- 7.2 days, and 428 (13.5%) of women remained
      hospitalized until delivery, with 324 (10.2%) delivering within 48 h. CONCLUSION:
      In this population of women receiving outpatient preterm-labor management
      services, 95.1% of excessive MUA or patient-reported symptoms of preterm labor
      were managed on an outpatient basis. Outpatient management allowed for
      appropriate identification and triage of women requiring hospital admission.

PMID- 15512720
TI  - Prevalence of hepatitis B and C in the maternity department of a Greek district
      hospital.
AB  - OBJECTIVE: To define the prevalence of infection with hepatitis B virus (HBV) and
      hepatitis C virus (HBC), and the modifications observed during the last 8 years,
      amongst parturients who gave birth in our department. DESIGN: This was a
      retrospective study. PATIENTS: The 5497 parturients who gave birth in our
      department between October 1994 and September 2002. RESULTS: On average, 3.87%
      (213) of the pregnant women tested positive for hepatitis B surface antigen;
      2.90% amongst pregnant Greek women and 4.67% amongst pregnant immigrant women.
      Among all pregnant women, 0.80% (44) tested positive for antibodies against HCV;
      0.16% amongst Greek women and 1.33% amongst immigrant women. CONCLUSIONS: HBV
      prevalence in pregnant women did not seem to be affected by the increase of
      immigrants in our obstetric population over the course of time. HCV prevalence in
      the pregnant women, however, did seem to follow the increase of immigrants in our
      obstetric population. Economic and security issues unfortunately deprive some
      neonates, born to mothers with HBV infection, from the use of hepatitis B
      immunoglobulin.

PMID- 15512721
TI  - Acceleration of fetal maturation by oxytocin-produced uterine contraction in
      pregnancies complicated with gestational diabetes mellitus: a preliminary report.
AB  - BACKGROUND: Prevention of the permanent sequelae of fetal hyperinsulinemia,
      namely hypertension and obesity, in infants born to mothers with gestational
      diabetes mellitus (GDM) has remained unresolved. Efforts to reduce fetal
      macrosomia by attempting to maintain blood sugar within a certain range have
      certainly failed. We have tried to eliminate fetal macrosomia by accelerating
      fetal maturation and delivery before the 36th week. METHODS: Acceleration of
      fetal maturation was achieved by endogenous release of thyrotropin-releasing
      hormone brought about by periodic fluctuations in fetal oxygenation resulting
      from oxytocin-produced uterine contractions. Fifteen patients with GDM at 33-35
      weeks, six of whom had previously given birth to a macrosomic fetus, agreed to
      participate in the study. Oxytocin was given for 6 h per day to produce regular
      contractions. In 13 patients it was given for 5 days, and in two patients for 7
      days to reach a lecithin/sphingomyelin (L/S) ratio indicative of fetal maturity.
      RESULTS: Eleven patients delivered vaginally after induction of labor and four
      delivered by Cesarean section. The mean Apgar score at 5 min was 9.13, and the
      mean birth weight was 2917 g (range 2100-3400 g). No newborn had respiratory
      difficulties, although four had short episodes of tachypnea. All were cared for
      in the regular nursery and all were discharged home with their mothers.
      CONCLUSION: Acceleration of fetal maturation, and delivery between 34 and 36
      weeks, appears to be a promising means to reduce or even eliminate the permanent
      sequelae of fetal hyperinsulinemia in pregnancies complicated by GDM.

PMID- 15512722
TI  - Labor course and delivery in epidural analgesia: a case-control study.
AB  - BACKGROUND: We aimed to establish if epidural analgesia is associated with a
      higher incidence of operative vaginal delivery, longer duration of labor and more
      frequent use of oxytocin than labor without analgesia. METHODS: We analyzed a
      cohort of 207 women with no risk factors who delivered with epidural analgesia in
      the labor unit of Spedali Civili, Brescia, Italy, during 2001. Length of the
      first and second stage of labor, mode of delivery, neonatal cord blood pH,
      neonatal Apgar score and neonatal outcomes were evaluated. RESULTS: Epidural
      analgesia was performed on request in 6%: in this group (group A) there were 141
      (68%) nulliparae and 66 (32%) pluriparae; mean ( +/- standard deviation)
      gestational age at delivery was 39.4 +/- 1.3 weeks (range: 34.1-41.5 weeks). In
      this group, 184 (89%) had vaginal delivery and 23 (11%) delivered by Cesarean
      section. Among controls (group B), 368 (89%) had a vaginal delivery and 46 (11%)
      delivered by Cesarean section; vacuum extraction was used in 18 deliveries (9%)
      in group A and in 13 deliveries (3%) in group B. The duration of the second stage
      of spontaneous labor in the nulliparae of group A was significantly longer than
      in group B. No statistically significant differences were found between mean
      umbilical artery pH values of groups A and B. CONCLUSION: Our results confirm
      that epidural analgesia does not affect the rate of Cesarean delivery, while
      increasing the use of oxytocin augmentation, the duration of the second stage of
      labor and the rate of instrumental vaginal delivery.

PMID- 15512723
TI  - The effects of veno-venous extracorporeal membrane oxygenation on hypoxic fetal
      lambs.
AB  - OBJECTIVE: The purpose of this study was to determine the applicability of veno
      venous extracorporeal membrane oxygenation (V-V ECMO) to support fetal
      oxygenation in utero. METHODS: An ECMO system with a centrifugal pump was applied
      to ten chronically instrumented fetal lambs, at 126 or 127 days of gestation.
      Blood was obtained through a double-lumen catheter inserted into the right
      atrium. After oxygenation, the blood was returned through a single-lumen catheter
      into either the carotid artery (veno-arterial; V-A ECMO) or the right atrium (V-V
      ECMO). After fetal hypoxia had been experimentally produced, V-A ECMO or V-V ECMO
      was instituted to maintain fetal oxygenation. We compared fetal blood gases with
      both routes of ECMO. RESULTS: Oxygen partial pressure (pO(2)) in the fetal
      cranial carotid artery decreased to 12.9 +/- 0.6 mmHg after reducing the fraction
      inspiratory oxygen of the mother. After instituting V-A ECMO, pO(2) was found to
      be 23.5 +/- 2.6 mmHg; after instituting V-V ECMO, pO(2) was found to be 20.3 +/-
      1.9 mmHg. Thus, fetal acidosis increased under both procedures. Fetal heart rate
      and blood pressure were not altered significantly during the experiments.
      CONCLUSIONS: This study indicates that V-V ECMO could more effectively and less
      traumatically maintain oxygenation in hypoxic fetal lambs.

PMID- 15512724
TI  - Pulmonary function after surfactant lung lavage followed by surfactant
      administration in infants with severe meconium aspiration syndrome.
AB  - OBJECTIVE: The effect of surfactant lung lavage (SLL) on pulmonary function was
      examined in neonates with severe form of meconium aspiration syndrome (MAS) (mean
      +/- standard deviation: birth weight, 3178.1 +/- 237.6 g; gestational age, 37.7
      +/- 1.8 weeks). METHODS: The infants were on mechanical ventilation and were
      subjected to SLL with Survanta. Dynamic compliance (Cdyn), airway resistance
      (Raw) and mean airway pressure (MAP) were obtained with use of the
      pneumotachometric method. Measurements of Cdyn, Raw, MAP and time constant (Tc)
      were compared in the study and control groups and between the groups before SLL
      and 24 and 48 h after SLL. RESULTS: A significant increase in Cdyn (from 1.06 +/-
      0.23 to 2.12 +/- 0.99 (ml/cmH(2)O)/kg) (p < 0.05) and a drop in both Raw (from
      264.7 +/- 41.5 to 146.6 +/- 39.4 (cmH(2)O/l)/s) and MAP (from 12.4 +/- 3.6 to 5.4
      +/- 2.1 cmH(2)O) were observed 48 hours after SLL. CONCLUSIONS: These data
      suggest that SLL is associated with a rapid and significant improvement in
      pulmonary mechanics, together with an improvement in oxygenation, in newborns
      with severe MAS. We found that the beneficial effects of SLL on pulmonary
      mechanics persisted for at least 48 h after introduction of the procedure.

PMID- 15512725
TI  - Neonatal hypopituitarism presenting with poor feeding, hypoglycemia and prolonged
      unconjugated hyperbilirubinemia.
AB  - The association between neonatal hypopituitarism and unconjugated
      hyperbilirubinemia has rarely been documented. We report a female infant who
      presented with persistent poor feeding, episodic borderline hypoglycemia and
      prolonged unconjugated hyperbilirubinemia; investigation revealed
      hypopituitarism. The diagnosis of hypopituitarism should therefore be considered
      in neonates presenting with prolonged unconjugated hyperbilirubinemia.

PMID- 15512726
TI  - Uterine artery Doppler and mid-trimester maternal plasma homocysteine in
      subsequent pre-eclampsia.
AB  - OBJECTIVE: To investigate whether mid-trimester maternal plasma homocysteine
      concentration is elevated in women who develop pre-eclampsia and in those women
      identified at high risk by abnormal uterine artery Doppler examination. METHODS:
      This was a multicenter study involving healthy women undergoing screening for pre
      eclampsia by uterine artery Doppler velocimetry at 22-24 weeks' gestation.
      Abnormal uterine artery blood flow was defined as a mean pulsatility index (PI)
      above the 95th centile (1.6). Controls (mean PI < 1.6) were matched for
      gestational age and date of blood sample collection. Maternal plasma homocysteine
      concentration was measured retrospectively using a chemiluminescent immunoassay.
      RESULTS: In total, 683 women were recruited. Maternal plasma homocysteine
      concentration did not vary with gestation. Maternal plasma homocysteine
      concentration in women who subsequently developed pre-eclampsia (n = 80, 12%) was
      not significantly different from women with uncomplicated pregnancies (n = 536,
      78%) (median 5.1, range 2.7-14.1 micromol/l vs. median 5.5, range 1.9-27.9
      micromol/l, p = 0.44). There were no significant differences in the maternal
      plasma homocysteine concentration in women with abnormal uterine artery Doppler
      findings (n = 275) compared with controls (n = 408), (median 5.6, range 2.6-17.7
      micromol/l vs. median 5.4, range 1.9-27.9 micromol/l, p = 0.13). CONCLUSION: Mid
      trimester maternal plasma homocysteine concentration is not elevated in women who
      developed pre-eclampsia even in those at high risk defined by abnormal uterine
      artery Doppler velocimetry.

PMID- 15512727
TI  - Megacystis-microcolon-intestinal hypoperistalsis syndrome: a case report.
AB  - Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a rare
      congenital disorder characterized by a dilated, non-obstructive urinary bladder
      and hypoperistalsis of the gastrointestinal tract, which is considered lethal.
      About 90 patients have been reported, predominantly female. We present the case
      of a female newborn with MMIHS in whom antenatal ultrasound was suggestive for
      the diagnosis, which was confirmed after delivery. Diagnostic features by
      antenatal ultrasound are described.

PMID- 15512755
TI  - Lumped parameter and feedback control models of the auto-regulatory response in
      the Circle of Willis.
AB  - The Circle of Willis (CoW) is a ring-like structure of blood vessels found
      beneath the hypothalamus at the base of the brain. Its main function is to
      distribute oxygen-rich arterial blood to the cerebral mass. A 1-dimensional model
      of the CoW has been created to simulate a series of possible clinical scenarios
      such as occlusions in afferent arteries, absent or string-like circulus vessels,
      or arterial infarctions. The model captures cerebral haemodynamic auto-regulation
      by using a proportional-integral-derivative (PID) controller to modify efferent
      resistances and maintain optimal efferent flowrates for a given circle geometry
      and afferent blood pressure. Results match limited clinical data and results
      obtained in prior studies to within 6%. In addition, a set of boundary conditions
      and geometry is presented for which the auto-regulated system cannot provide the
      necessary efferent flowrates and perfusion, representing a condition with
      increased risk of stroke and highlighting the importance of modelling the
      haemodynamics of the CoW. The system model created is computationally simple so
      it can be used to identify at-risk cerebral arterial geometries and conditions
      prior to surgery or other clinical procedures.

PMID- 15512756
TI  - Bone remodelling of a proximal femur with the thrust plate prosthesis: an in
      vitro case.
AB  - The key to the development of a successful implant is an understanding of the
      effect of bone remodelling on its long-term fixation. In this study, clinically
      observed patterns of bone remodelling have been compared with computer-based
      predictions for one particular design of prosthesis, the Thrust Plate Prosthesis
      (Centerpulse Orthopedics, Winterthur, Switzerland). Three-dimensional finite
      element models were created using geometrical and bone density data obtained from
      CT scanning. Results from the bone remodelling simulation indicated that varying
      the relative rate of bone deposition/resorption and the interfacial conditions
      between the bone and the implant could produce the trend towards the two
      clinically observed patterns of remodelling.

PMID- 15512757
TI  - Validation of a fluid-structure interaction model of a heart valve using the
      dynamic mesh method in fluent.
AB  - Simulations of coupled problems such as fluid-structure interaction (FSI) are
      becoming more and more important for engineering purposes. This is particularly
      true when modeling the aortic valve, where the FSI between the blood and the
      valve determines the valve movement and the valvular hemodynamics. Nevertheless
      only a few studies are focusing on the opening and closing behavior during the
      ejection phase (systole). In this paper, we present the validation of a FSI model
      using the dynamic mesh method of Fluent for the two-dimensional (2D) simulation
      of mechanical heart valves during the ejection phase of the cardiac cycle. The
      FSI model is successfully validated by comparing simulation results to
      experimental data obtained from in vitro studies using a CCD camera.

PMID- 15512758
TI  - Congruency effects on load bearing in diarthrodial joints.
AB  - Modelling load bearing in diarthrodial joints is challenging, due to the
      complexity of the materials, the boundary and interface conditions and the
      geometry. The articulating surfaces are covered with cartilage layers that are
      filled with a fluid that plays a major role in load bearing [Mow, V.C., Holmes,
      M.H., Lai, W.M. (1984) "Survey article: fluid transport and mechanical properties
      of articular cartilage: a review", Journal of Biomechanics 17(5), 377-394].
      Researchers have tended to approximate joint geometry using axisymmetry
      [Donzelli, P.S., Spilker, R.L., Ateshian, G.A., Mow, V.C. (1999) "Contact
      analysis of biphasic transversely isotropic cartilage layers and correlations
      with tissue failure", Journal of Biomechanics 32, 1037-1047], often with a
      rounded upper articulating surface, creating a form of Hertz problem [Donzelli,
      P.S., Spilker, R.L., Ateshian, G.A., Mow, V.C. (1999) "Contact analysis of
      biphasic transversely isotropic cartilage layers and correlations with tissue
      failure", Journal of Biomechanics 32, 1037-1047]. However, diarthrodial joints
      (shoulder, hip and knee) are equipped with peripheral structures (glenoid labrum,
      acetabular labrum and meniscus, respectively) that tend to deepen the joint
      contact and thus cause initial contact to be established at the periphery of the
      joint rather than "centrally". The surface geometries are purposefully
      incongruent, and the incongruency has a significant effect on the stresses,
      pressures and pressure gradients inside the tissue. The models show the
      importance of the peripheral structures and the incongruency from a load-bearing
      perspective. Joint shapes must provide a compromise between demands for load
      bearing, lubrication and the supply of nutrients to the chondrocytes of the
      cartilage and cells of the peripheral structures. Retention and repair of the
      functionality of these peripheral structures should be a prime consideration in
      any surgical treatment of an injured joint.

PMID- 15512759
TI  - A 3D generic inverse dynamic method using wrench notation and quaternion algebra.
AB  - In the literature, conventional 3D inverse dynamic models are limited in three
      aspects related to inverse dynamic notation, body segment parameters and
      kinematic formalism. First, conventional notation yields separate computations of
      the forces and moments with successive coordinate system transformations.
      Secondly, the way conventional body segment parameters are defined is based on
      the assumption that the inertia tensor is principal and the centre of mass is
      located between the proximal and distal ends. Thirdly, the conventional kinematic
      formalism uses Euler or Cardanic angles that are sequence-dependent and suffer
      from singularities. In order to overcome these limitations, this paper presents a
      new generic method for inverse dynamics. This generic method is based on wrench
      notation for inverse dynamics, a general definition of body segment parameters
      and quaternion algebra for the kinematic formalism.

PMID- 15512760
TI  - The effects of changing bone and muscle size on limb inertial properties and limb
      dynamics: a computer simulation.
AB  - The magnitude and distribution of bone and muscle mass within limbs affect limb
      inertial properties, maximum movement speed and the energy required to maintain
      submaximal movements. Musculoskeletal modeling and movement simulations were used
      to determine how changes in bone and muscle cross-sectional area (and thus mass)
      affect human thigh and shank inertial properties, the maximum speed of unloaded
      single-leg cycling and the energy required to sustain submaximal single-leg
      cycling. Depending on initial conditions, shank moments of inertia increased 61
      72 kg cm2 per kg added bone and 72-100 kg cm2 per kg added muscle. Thigh moments
      of inertia increased 46-63 kg cm2 per kg bone and 180-225 kg cm2 per kg muscle.
      Maximum unloaded cycling velocity increased with increased muscle mass
      (approximately 2.2-2.9 rpm/kg muscle), but decreased with increased cortical bone
      mass (approximately 2.0-2.8 rpm/kg bone). The internal work associated with
      unloaded submaximal cycling increased with increased muscle mass (approximately
      0.42-0.48 J/kg muscle) and bone mass (approximately 0.18-0.22 J/kg bone).

PMID- 15512761
TI  - Microwave thermotherapy of prostatic enlargement--analysis of radiometric
      thermometry using a hybrid bio-heat equation.
AB  - The radiometric temperature measurement included in a commercial device for
      transurethral microwave thermotherapy (TUMT) of the prostate was investigated
      utilizing both phantom experiments and computer simulations. Two finite element
      (FE) models were developed. One is in part based on the experimental results, and
      serves as a complement to the experiments, while the other describes a perfused
      tissue situation for which the hybrid bio-heat equation was used to model the
      thermal effects of blood perfusion. The aim of the study was to investigate how
      the radiometric thermometer is affected by the temperature close to the antenna,
      and to analyze the relation between blood perfusion, temperature distribution and
      radiometric temperature measurement. It was found that the radiometric
      temperature was affected to a greater extent by the temperature very close to the
      antenna, in contrast to what has been expected in previous studies. The blood
      perfusion was found to mainly affect the temperature distribution outside the
      maximum temperature (located 2-3 mm outside the cooled catheter). Thus, the
      relation between the radiometric temperature and the temperature in the treated
      area is relatively weak.

PMID- 15512762
TI  - Changes in the fabric and compliance tensors of cancellous bone due to trabecular
      surface remodeling, predicted by a digital image-based model.
AB  - Fabric and compliance tensors of a cube of cancellous bone with a complicated
      three-dimensional trabecular structure were obtained for trabecular surface
      remodeling by using a digital image-based model combined with a large-scale
      finite element method. Using mean intercept length and a homogenization method,
      the fabric and compliance tensors were determined for the trabecular structure
      obtained in the computer remodeling simulation. The tensorial quantities obtained
      indicated that anisotropic structural changes occur in cancellous bone adapting
      to the compressive loading condition. There were good correlations between the
      fabric tensor, bone volume fraction, and compliance tensor in the remodeling
      process. The result demonstrates that changes in the structural and mechanical
      properties of cancellous bone are essentially anisotropic and should be expressed
      by tensorial quantities.

PMID- 15512763
TI  - A finite element model of the human buttocks for prediction of seat pressure
      distributions.
AB  - Seating comfort is becoming increasingly important for the automotive industry.
      Car manufacturers use seating comfort to distinguish their products from those of
      competitors. However, the development and design of a new, more comfortable seat
      is time consuming and costly. The introduction of computer models of human and
      seat will accelerate this process. The contact interaction between human and seat
      is an important factor in the comfort sensation of subjects. This paper presents
      a finite element (FE) model of the human buttocks, able to predict the pressure
      distribution between human and seating surface by its detailed and realistic
      geometric description. A validation study based on volunteer experiments shows
      reasonable correlation in pressure distributions between the buttocks model and
      the volunteers. Both for simulations on a rigid and a soft cushion, the model
      predicts realistic seat pressure distributions. A parameter study shows that a
      pressure distribution at the interface between human and seat strongly depends on
      variations in human flesh and seat cushion properties.

PMID- 15512764
TI  - A new computational efficient approach for trabecular bone analysis using beam
      models generated with skeletonized graph technique.
AB  - Micro-finite element (FE) analysis is a well established technique for the
      evaluation of the elastic properties of trabecular bone, but is limited in its
      application due to the large number of elements that it requires to represent the
      complex internal structure of the bone. In this paper, we present an alternative
      FE approach that makes use of a recently developed 3D-Line Skeleton Graph
      Analysis (LSGA) technique to represent the complex internal structure of
      trabecular bone as a network of simple straight beam elements in which the beams
      are assigned geometrical properties of the trabeculae that they represent. Since
      an enormous reduction of cputime can be obtained with this beam modeling
      approach, ranging from approximately 1,200 to 3,600 for the problems investigated
      here, we think that the FE modeling technique that we introduced could
      potentially constitute an interesting alternative for the evaluation of the
      elastic mechanical properties of trabecular bone.

PMID- 15512765
TI  - Evaluation of parallel decomposition methods for biomechanical optimizations.
AB  - As the complexity of musculoskeletal models continues to increase, so will the
      computational demands of biomechanical optimizations. For this reason, parallel
      biomechanical optimizations are becoming more common. Most implementations
      parallelize the optimizer. In this study, an alternate approach is investigated
      that parallelizes the analysis function (i.e., a kinematic or dynamic simulation)
      called repeatedly by the optimizer to calculate the cost function and
      constraints. To evaluate this approach, a system identification problem involving
      a kinematic ankle joint model was solved using a gradient-based optimizer and
      three parallel decomposition methods: gradient calculation decomposition,
      analysis function decomposition, or both methods combined. For a given number of
      processors, analysis function decomposition exhibited the best performance
      despite the highest communication and synchronization overhead, while gradient
      calculation decomposition demonstrated the worst performance due to the fact that
      the necessary line searches were not performed in parallel. These findings
      suggest that the method of parallelization most commonly used for biomechanical
      optimizations may not be the most efficient, depending on the optimization
      algorithm used. In many applications, the best computational strategy may be to
      focus on parallelizing the analysis function.

PMID- 15512766
TI  - Failure of total hip arthroplasties. Numerical modeling of debris formation
      through plastic strains.
AB  - The life span of a total hip prosthesis is one of the main points on which the
      long-term success of arthroplasties depends. It is, by now, widely recognized
      that hip arthroplasty failure is mainly due to the aseptic loosening resulting
      from the presence of wear debris forming at the contact interface between the
      femoral head and the cup of the acetabulum. The size of these particles varies
      from a few micrometers to some tens of micrometers or more. The main aim of this
      study was therefore to investigate the formation of debris in the microscopic
      size range. For this purpose, a numerical study was carried out on various
      mechanisms leading to plastic deformations, which can lead to damage and wear in
      material. Numerical analyses were performed with a laboratory software program
      LMGC90, on the evolution of the plastic strains involved in various wear
      mechanisms on the microscopic scale.

PMID- 15512767
TI  - Analysis of mineral deposition in turkey tendons and self-assembled collagen
      fibers using mechanical techniques.
AB  - During limb movement and locomotion, animals store elastic energy in the tendons
      of the feet, legs, and other limbs. In the turkey, much of the force generated by
      the gastrocnemius muscle during locomotion is stored as elastic energy through
      deformation of the tendon. During growth and development, the leg tendons in some
      avians, including turkeys, mineralize and result in an increase in tensile
      strength and modulus. The purpose of our study was to evaluate the effects of
      mineralization on elastic energy storage and transmission in turkey tendons.
      Elastic and viscous stress-strain curves and elastic energy storage behavior were
      used to compare the behavior of mineralized turkey gastrocnemius tendons and
      mineralized self-assembled type I collagen fibers. Based on analysis of these two
      systems, we concluded that a simple mineralized fibrillar collagenous substrate
      can mimic the behavior of a more complex fibrillar collagenous substrate such as
      mineralized turkey tendon; however, the exact mechanism of mineralization may be
      different between the two substrates. Changes in mechanical properties of turkey
      tendon were consistent with a model in which mineralization appears to increase
      the effective collagen fibril length by efficiently transferring stress between
      neighboring collagen fibrils. Mineralization in self-assembled collagen fibers
      increased elastic energy storage less efficiently as compared with turkey tendon
      suggesting that the noncollagenous components of mineralizing tissue may act to
      promote collagen fibril to collagen fibril interactions.

PMID- 15512768
TI  - Regulation of gelatinases expression by cytokines, endotoxin, and pharmacological
      agents in the human osteoarthritic knee.
AB  - We examined the amount of gelatinases (matrix metalloproteinase-2 and -9 [MMP-2
      and MMP-9] in a series of chondral, meniscal, and synovial cultures of early
      osteoarthritis (OA) after treatment with or without catabolic cytokines. These
      included interleukin-1alpha (IL-1alpha) and tumor necrosis factor-alpha (TNF
      alpha), lipopolysaccharide (LPS), and pharmacological agents, including
      plasmin/serine proteinase antagonist aprotinin, protein synthesis inhibitor
      cycloheximide, and protein kinase C (PKC) inhibitors staurosporine, H7, and
      Go6976 for investigation of their effects on MMP-2 and -9 production in OA.
      Gelatin zymography revealed that IL-alpha, TNF-alpha, and LPS could elevate MMP-2
      secretion in all tissue cultures and also increase MMP-9 production in all
      synovial and some meniscal cultures. In contrast, aprotinin, cycloheximide,
      staurosporine, H7, and Go6976 could suppress MMP-2 secretion in all tissue
      cultures and also decrease MMP-9 production in all synovial and some meniscal
      cultures. Our data indicate that catabolic cytokines and LPS may promote tissue
      destruction and disintegration of extracellular matrix in early OA. Agents that
      target on the PKC pathway, plasmin/serine proteinase or protein synthesis for MMP
      2 and -9 in early OA may inhibit the production of MMPs. These findings might
      contribute to the design of more efficacious therapies.

PMID- 15512769
TI  - Oncothanin, a peptide from the alpha3 chain of type IV collagen, modifies
      endothelial cell function and inhibits angiogenesis.
AB  - Previous studies from our group and the group of the Department of Biochemistry
      at the University of Rheims, France [corrected] have shown that basement membrane
      (BM) collagen from anterior lens capsule type IV collagen (ALC-COL IV) and
      peptides from the noncollagenous domain (NC1) of the alpha3(IV) [corrected]
      chain, corresponding to residues 185-203 and 179-208, inhibit tumor cell
      proliferation, specifically through the interaction of the -SNS- tripeptide
      (residues 189-191) with the CD47/alphavbeta3 integrin receptor complex. Data
      presented here demonstrate that the alpha3(IV)185-203 and the alpha3(IV)179-208
      peptides, from here forward [corrected] designated as oncothanin, regulate
      endothelial cell (EC) proliferation, adhesion, and motility which [corrected]
      ultimately influence angiogenesis. The data also indicate that oncothanin, when
      used as a chemoattractant, greatly enhanced EC chemotaxis. In contrast,
      pretreatment of EC with oncothanin inhibited chemotaxis toward several different
      chemoattractants. When oncothanin was used as a substrate, it enhanced EC
      adhesion that was inhibited when pretreated with same. Analysis of angiogenesis
      by EC differentiation (tube formation), aortic ring microvessel formation
      [corrected] and the chorioallantoic membrane assay, [corrected] demonstrate that
      oncothanin, but not the control medium or peptides, inhibits angiogenesis. In the
      EC differentiation assay, oncothanin completely inhibited tube formation at 25
      microg/ml, whereas peptides with comparable sequences, that lacked [corrected]
      the -SNS- sequence, from ALC-COL IV NC1 domains alpha1 and alpha2 chains failed
      to inhibit tube formation. The data support the hypothesis that ALC-COL IV and
      oncothanin inhibit angiogenesis by modulation of EC function.

PMID- 15512770
TI  - Expression of transcription factor Sox9 in rat L6 myoblastic cells.
AB  - Muscle-derived cells can differentiate into chondrogenic cells. In our present
      study, we investigated the pattern of expression of Sox9, a transcription factor
      known to play a key role in chondrogenesis, in a rat myoblastic cell line, L6. In
      addition, we evaluated expression of type II collagen and myogenic regulatory
      markers by reverse-transcript polymerase chain reaction. We also investigated the
      effect of transforming growth factor (TGF)-beta3, which is known to induce
      chondrogenesis, on Sox9 mRNA expression. On the first day of culture, we observed
      a high expression of Sox9. However, on the seventh day of culture, there was a
      decline in the level of Sox9 and type II collagen mRNAs and an increased
      expression of Myf5 and myogenin mRNAs. Sox9 mRNA expression was increased after
      stimulation of TGF-beta3 at 2, 6, and 24 hr. Cartilage nodules were observed in
      L6 cells treated with TGF-beta3 and dexamethasone. These results indicated that
      L6 myoblasts originally possess the capacity to differentiate into chondrogenic
      cells, but that capacity is lost as the cells differentiate toward the myogenic
      lineage. In addition, TGF-beta3 may modulate Sox9 mRNA expression in L6 cells and
      retain the capacity to differentiate into chondrogenic lineage.

PMID- 15512771
TI  - Cyclic loading can denature type II collagen in articular cartilage.
AB  - We sought to explain previously reported associations between osteoarthritis,
      cartilage collagen denaturation, and repetitive mechanical loading. Eighty
      specimens of cartilage-on-bone were obtained from bovine patella grooves. After
      soaking in protease inhibitors, specimens were subjected to 3,600 cycles of
      compressive loading by means of a flat indenter. Loaded cartilage was supported
      by adjacent cartilage and subchondral bone. Peak stress ranged between 3.5 MPa
      and 14 MPa. Collagen denaturation was assessed by an inhibition ELISA assay using
      the col2-3/4 m antibody. Results showed that denaturation increased with loading
      severity, from 2% in control (unloaded) cartilage to 7.5% at 14 MPa (p < .0003).
      Collagen and glycosaminoglycan content of cartilage were unchanged after loading.
      Denaturation was largely unaffected by the absence of protease inhibitors or when
      chondrocytes were killed by repeated freeze-thaw cycles prior to loading. We
      conclude that vigorous cyclic mechanical loading causes an immediate dose-related
      increase in collagen denaturation in bovine articular cartilage.

PMID- 15512772
TI  - Cathepsins B and L increased during response of periodontal ligament cells to
      mechanical stress in vitro.
AB  - Cathepsin is a typical and well-characterized lysosomal cysteine protease that,
      under pathological conditions, is involved in tissue destruction. A recent
      immunocytochemical study demonstrated that cathepsins B (CAB) and L (CAL) were
      localized in the periodontal ligament (PDL) of the rat molar, and they were
      expressed in compressed sites during experimental tooth movement. Further, we
      demonstrated previously that the levels of CAB and CAL in gingival crevicular
      fluid increased during orthodontic tooth movement. Therefore, CAB and CAL may
      play important roles in the process of collagen degradation during orthodontic
      tooth movement, and our in vitro study examined the secretion of CAB and CAL in
      PDL cells following mechanical stress. PDL cells were subjected to 0.5, 1.0, 2.0,
      or 3.0 g/cm2 of compression force or an increase in surface area by tension force
      of 0.28%, 0.95%, 1.72%, or 2.50% for 24 hr. For detection of CAB and CAL in
      conditioned medium, commercially available ELISA kits were used. We found
      compression and tension significantly increased the secretions of both CAB and
      CAL in PDL cells, which were exhibited in a time- and force magnitude-dependent
      manner. The compression-stimulated secretion of CAB was increased approximately 3
      fold and that of CAL 4-fold, as compared with the control. Further, tension
      stimulated secretion of CAB was increased by 1.5-fold and that of CAL 2-fold
      compared with the control. When analyzed using a semiquantitative polymerase
      chain reaction assay, CAB and CAL mRNA were increased in response to both
      compression and tension forces. These findings demonstrated that mechanical
      stress (compression and tension forces) causes an increase in secretion of CAB
      and CAL in PDL cells in vitro.

PMID- 15512773
TI  - Stiffness of the healing medial collateral ligament of the mouse.
AB  - The knee joints of mice can serve as a model for studying knee ligament
      properties. The goal of our study was to measure the structural stiffness of the
      medial collateral ligament (MCL) of the murine knee. A tensile test was developed
      for this purpose. First 84 femur-MCL-tibia complexes of 11-week-old C57Black6
      mice were tested. Of four groups (n = 14 per group) the right MCL was ruptured.
      The mice were sacrificed at 1.5, 3, 6, and 9 weeks after the operation. The other
      two groups served as controls at 0 and 9 weeks after the operation. Absolute
      values of the structural stiffness of the healed MCLs at 1.5 weeks were initially
      significantly lower than their unoperated controls, but were not different from
      normal values at three, six, and nine weeks of healing. The structural stiffness
      of the unoperated controls increased by 11% at 20 weeks compared to 11 weeks of
      age.

PMID- 15512775
TI  - Tumour angiogenesis, vascular biology and enhanced drug delivery.
AB  - It is now common knowledge that for a solid tumour to become life-threatening
      clinically, an adequate blood supply to the neoplasm has to be established.
      Although neovascularisation via angiogenesis leads to a subsequent rapid growth
      of the tumour mass, it provides the most reliable route by which neoplastic cells
      may be reached by cytotoxics. In addition, for a majority of tumours, the
      lesion's vasculature is more permeable and tortuous than that of the surrounding
      healthy host tissue. Such deviation potentiates selective delivery of drugs to be
      achieved. This review examines, from various viewpoints, the area of tumour
      angiogenesis and vascularisation, currently one of the most fertile and active
      fields of cancer research.

PMID- 15512776
TI  - Liposomes modified with cyclic RGD peptide for tumor targeting.
AB  - Cyclic RGD peptide anchored sterically stabilized liposomes (RGD-SL) were
      investigated for selective and preferential presentation of carrier contents at
      angiogenic endothelial cells overexpressing alphavbeta3 integrins on and around
      tumor tissue and thus for assessing their targetabilty. Liposomes were prepared
      using distearoylphosphatidylcholine (DSPC), cholesterol and
      distearoylphosphatidylethanolamine-polyethyleneglycol-RGD peptide conjugate (DSPE
      PEG-RGD) in a molar ratio 56:39:5. The control RAD peptide anchored sterically
      stabilized liposomes (RAD-SL) and liposome with 5 mol% PEG (SL) without peptide
      conjugate which had similar lipid composition were used for comparison. The
      average size of all liposome preparations prepared was approximately 105 nm and
      maximum drug entrapment was 10.5+/- 1.1%. In vitro endothelial cell binding of
      liposomes exhibited 7-fold higher binding of RGD-SL to HUVEC in comparison to the
      SL and RAD-SL. Spontaneous lung metastasis and angiogenesis assays show that RGD
      peptide anchored liposomes are significantly (p<0.01) effective in the prevention
      of lung metastasis and angiogenesis compared to free 5-FU, SL and RAD-SL. In
      therapeutic experiments, 5-FU, SL, RGD-SL and RAD-SL were administered
      intravenously on day 4 at the dose of 10 mg 5-FU/kg body weight to B16F10 tumor
      bearing BALB/c mice resulting in effective regression of tumors compared with
      free 5-FU, SL and RAD-SL. Results indicate that cyclic RGD peptide anchored
      sterically stabilized liposomes bearing 5-FU are significantly (p<0.01) active
      against primary tumor and metastasis than the non-targeted sterically stabilized
      liposomes and free drug. Thus cyclic RGD peptide anchored sterically stabilized
      liposomes hold potential of targeted cancer chemotherapeutics.

PMID- 15512777
TI  - Interaction of nucleoside analogues with nucleoside transporters in rat brain
      endothelial cells.
AB  - A number of nucleoside analogues, consisting of antiviral compounds and agents
      designed as adenosine A1 receptor agonists, were examined for nucleoside
      transporter affinity using an in vitro model of the blood-brain barrier (BBB),
      the rat brain endothelial cell line, RBE4. Structure-activity relationships (SAR)
      were also performed to identify the key structural requirements for transporter
      recognition and the suitability of these systems for carrier-mediated strategies
      to deliver therapeutics across the BBB. Adenosine receptor agonists did not show
      transport affinity for concentrative nucleoside carriers, but exhibited affinity
      for equilibrative systems (Ki=10.8-97.9 microM) within the range of Kms for
      natural substrates. However, none of the antiviral compounds tested in this study
      showed affinity for either class of nucleoside transporter. SAR studies suggest
      that the hydroxyl group located at the 3'-position of the ribose moiety is an
      essential requirement for transporter recognition. This may explain the inability
      of nucleoside derived anti-viral compounds to use these systems despite the
      significant structural homology with naturally occurring nucleosides. Sites have
      also been identified which accommodate structural additions with retention of
      carrier affinity, suggesting that compounds which fail to penetrate the BBB could
      be attached to these sites for carrier-mediated delivery using a prodrug
      strategy.

PMID- 15512778
TI  - Enhanced delivery of octreotide to the brain via transnasal iontophoretic
      administration.
AB  - Transnasal drug delivery affords an opportunity to circumvent the blood-brain
      barrier and gain direct access to the brain. To date, this approach has used a
      relatively passive process relying on drug instillation high into the nasal
      cavity, formulation and gravity for drug delivery. The present study examined the
      use of an applied electrical field (transnasal iontophoresis or electrotransport)
      to actively drive a charged peptide, octreotide, into the rabbit brain. A simply
      designed electrode containing a reservoir of octreotide was placed deep into the
      nasal cavity on both sides. A return electrode was applied to the back of the
      head and a current strength of 3.0 mA was applied for 60 min. In control rabbits,
      electrodes were placed into the nasal cavity, but no current was applied (passive
      delivery). Additional control animals were given a bolus intra-arterial injection
      of octreotide. At the conclusion of drug delivery, animals were sacrificed and
      samples of brain, spinal cord, cerebrospinal fluid (CSF) and plasma were taken
      for measurement of octreotide levels by radioimmunoassay (RIA). In a second
      experiment, rabbits were exsanguinated prior to drug delivery to measure the
      ability of iontophoresis to transport octreotide into the brain in the absence of
      blood or CSF circulation. In both experiments, transnasal iontophoresis resulted
      in significantly elevated levels of octreotide in the brain, although results
      varied considerably due to electrode and tissue damage related to problems with
      electrode insertion into the rabbit's nasal cavity. Octreotide was present in
      samples extending from the olfactory bulb to the cerebellum with 2- to 13-fold
      increases in active compared to control/passive animals. High and sustained
      levels of octreotide were also present in the blood following transnasal
      delivery, but there were negligible amounts of octreotide in the brain following
      systemic administration indicating that the blood was not a significant route for
      drug redistribution. The results demonstrate that transnasal electrotransport is
      a unique, minimally invasive approach for enhancing drug delivery to the brain.

PMID- 15512779
TI  - Chitosan-DNA nanoparticles: effect on DNA integrity, bacterial transformation and
      transfection efficiency.
AB  - While somatic gene therapy has the potential to treat many genetic disorders,
      recent clinical trials suggest that an efficient and safe delivery vehicle for
      successful gene therapy is lacking. The current study examines the influence of
      two different preparation (the solvent evaporation method and the complex
      coacervation method) methods on the encapsulation of a model plasmid with
      chitosan. The ability of different molecular weights of chitosan to form
      nanoparticles with a plasmid, and particulated polymers to stabilize a plasmid in
      a supercoiled form, were examined by agarose gel electrophoresis. Protection of
      encapsulated pDNA offered by these nanoparticles from nuclease attack was
      confirmed by assessing degradation in the presence of DNase I, and the
      transformation of the plasmids with incubated nanoparticles were examined by beta
      galactosidase assay. Model pDNA existed as a mixture of both supercoiled (84.2%)
      and open circular (15.8%) forms. Our results demonstrated that supercoiled forms
      decreased while open circular forms and fragmented linear forms increased during
      the preparation of formulations. F1 formulation prepared by the complex
      coacervation method protected the supercoiled form of pDNA effectively. There
      weren't any significant changes in nanoparticle size and zeta potential values at
      pH 5.5 for a period of 3 months, but differences in particle sizes were observed
      after lyophilization with a cryoprotective agent. The efficiency of nanoparticles
      mediated transformation to Escherichia coli cells was significantly higher than
      naked DNA or poly-L-lysine (PLL)-DNA polycation complexes. The transfection
      studies were performed in COS-7 cells. A 3-fold increase in gene expression was
      produced by nanoparticles as compared to the same amount of naked plasmid DNA
      (pDNA). These observations suggest that formulations with high molecular weight
      (HMW) chitosan can be an effective non-viral method of gene vector in animal
      studies.

PMID- 15512780
TI  - Starch microparticles as oral vaccine adjuvant: antigen-dependent uptake in mouse
      intestinal mucosa.
AB  - An oral vaccine formulation comprised of starch microparticles with conjugated
      antigens is being developed. In this report we have examined the uptake of such
      microparticles by the intestinal mucosa and examined whether the conjugated
      antigen can influence the uptake. Two model antigens were used: recombinant
      cholera toxin B subunit (rCTB), which is known to bind to the ubiquitous GM1
      receptor, and human serum albumin (HSA) which is not known to have any specific
      binding properties. The uptake was studied in mouse ligated intestinal loops into
      which the microparticles were injected. The intestinal loops were excised, fixed
      in ice-cold 95% ethanol. Entire specimens were mounted, exposed to fluorescence
      labeled reagents staining the cytoskeleton, the particles and/or M cells and
      examined in a confocal laser-scanning microscope. A qualitative difference in the
      uptake of the rCTB- and HSA-conjugated microparticles was seen. The rCTB
      conjugated microparticles were found both in villi and in the follicles of the
      Peyer's patches. HSA-conjugated microparticles could only be detected in the
      follicles of the Peyer's patches and not in villi. The rCTB conjugated to the
      microparticles did not lose its ability to bind the GM1-receptor, as shown with a
      GM1-ELISA, and the uptake of rCTB-conjugated microparticles in villi is most
      probably facilitated by the rCTB binding to the GM1-receptor. The qualitative
      difference in uptake could be of importance for the development of an immune
      response as the cytokine and chemokine microenvironment during antigen
      presentation will decide the differentiation of the immune response induced.

PMID- 15512781
TI  - Norfloxacin-poly(L-lysine citramide imide) conjugates and structure-dependence of
      the drug release.
AB  - Norfloxacin (Nflx), an antibiotic which is active against some intracellular
      bacteria, was coupled to a polymeric carrier, namely poly(L-lysine citramide) via
      a lysine or an ethylcarbamate spacer to obtain a macromolecular prodrug. The
      carrier, which derived from the two metabolites citric acid and L-lysine, is
      known to be biocompatible and slowly degradable under slight acidic conditions.
      Conjugates were characterised by UV, 1H and 13C NMR and SEC. The presence of
      Norfloxacin and the lysine type spacer caused chain aggregation, due to a
      probable physical cure. The release of Norfloxacin from these prodrugs and from a
      prodrug where Norfloxacin is bound to the carrier backbone without spacer arm was
      investigated comparatively in vitro. Conjugation via a carbamate-type linkage
      appeared as a method to achieve the release of Norfloxacin from a PLCA-type
      conjugate at neutral.

PMID- 15512785
TI  - Anti-insulin receptor autoantibodies are not required for type 2 diabetes
      pathogenesis in NZL/Lt mice, a New Zealand obese (NZO)-derived mouse strain.
AB  - The New Zealand obese (NZO) mouse strain shares with the related New Zealand
      black (NZB) strain a number of immunophenotypic traits. Among these is a high
      proportion of B-1 B lymphocytes, a subset associated with autoantibody
      production. Approximately 50% of NZO/HlLt males develop a chronic insulin
      resistant type 2 diabetes syndrome associated with 2 unusual features: the
      presence of B lymphocyte-enriched peri-insular infiltrates and the development of
      anti-insulin receptor autoantibodies (AIRAs). To establish the potential
      pathogenic contributions of B lymphocytes and AIRAs in this model, a disrupted
      immunoglobulin heavy chain gene (Igh-6) congenic on the NZB/BlJ background was
      backcrossed 4 generations into the NZO/HlLt background and was then intercrossed
      to produce mice that initially segregated for wild-type versus the mutant Igh-6
      allele and thus permitted comparison of syndrome development. A new flow
      cytometric assay (AIRA binding to transfected Chinese hamster ovary cells stably
      expressing mouse insulin receptor) showed IgM and IgG subclass AIRAs in serum
      from Igh-6 intact males, but not in Igh-6null male serum. However, the absence of
      B lymphocytes and antibodies distinguishing mutant from wild-type males failed to
      significantly affect diabetes-free survival. The Igh-6null males gained weight
      less rapidly than wild-type males, probably accounting for a retardation, but not
      prevention, of hyperglycemia. Thus, AIRA and the B-lymphocyte component of the
      peri-insulitis in chronic diabetics were not essential either to development of
      insulin resistance or to eventual pancreatic beta cell failure and loss. A new
      substrain, designated NZL, was generated by inbreeding Igh-6 wild-type
      segregants. Currently at the F10 generation, NZL mice exhibit the same juvenile
      onset obesity as NZO/HlLt males, but develop type 2 diabetes at a higher
      frequency (> 80%). Also, unlike NZO/HlLt mice that are difficult to breed, the
      NZL/Lt strain breeds well and thus offers clear advantages to obesity/diabetes
      researchers.

PMID- 15512786
TI  - Sensory nerve innervation of epineurial arterioles of the sciatic nerve
      containing calcitonin gene-related peptide: effect of streptozotocin-induced
      diabetes.
AB  - The authors have determined that epineurial arterioles of the sciatic nerve are
      innervated by nonadrenergic, noncholinergic nerves that contribute to the
      regulation of vasodilation. Using immunohistochemistry, the authors determined
      that nerves innervating epineurial arterioles contain the neuropeptide calcitonin
      gene-related peptide (CGRP). Using streptozotocin-induced diabetic rats, the
      authors demonstrated that CGRP content in sensory nerves innervating epineurial
      arterioles and vasodilation in response to exogenous CGRP was decreased. In
      summary, epineurial arterioles of the sciatic nerve are innervated by sensory
      nerves containing the neuropeptide CGRP. The diabetes-like condition induced by
      streptozotocin reduces the content of CGRP in these nerves and exogenous CGRP
      mediated vasodilation. CGRP is likely an important regulator of vascular tone and
      compromising its function could contribute to nerve ischemia and diabetic
      neuropathy.

PMID- 15512787
TI  - Effect of alpha-lipoic acid on lipid profile in rats fed a high-fructose diet.
AB  - This study investigated the effect of administration of alpha-lipoic acid (LA) on
      lipid metabolism in high fructose-fed insulin-resistant rats. High-fructose
      feeding (60 g/100 g diet) to normal rats resulted in a significant increase in
      the concentrations of cholesterol, triglycerides (TGs), free fatty acids (FFAs),
      and phospholipids in plasma, liver, kidney, and skeletal muscle. Reduced
      activities of lipoprotein lipase (LPL) and lecithin cholesterol acyl transferase
      (LCAT) and increased activity of the lipogenic enzyme hydroxymethylglutaryl
      coenzyme A (HMG-CoA) reductase were observed in plasma and liver. High-density
      lipoprotein cholesterol (HDL-C) was significantly lowered and very low-density
      lipoprotein cholesterol (VLDL-C) and low-density lipoprotein cholesterol (LDL-C)
      were significantly elevated. Treatment with LA (35 mg/kg body weight
      intraperitoneal) reduced the effects of fructose. The rats showed near-normal
      levels of lipid components on plasma and tissues. Activities of key enzymes of
      lipid metabolism were also restored to normal values. Cholesterol distribution in
      the plasma lipoproteins was normalized, resulting in a favorable lipid profile.
      This study demonstrates that LA can alter lipid metabolism in fructose-fed
      insulin-resistant rats and may have implications in the treatment of insulin
      resistance.

PMID- 15512788
TI  - Gene combination transfer to block autoimmune damage in transplanted islets of
      Langerhans.
AB  - Islet transplantation therapy would be applicable to a wider range of diabetic
      patients if donor islet acceptance and protection were possible without systemic
      immunosuppression of the recipient. To this aim, gene transfer to isolated donor
      islets ex vivo is one method that has shown promise. This study examines the
      combined effect of selected immunomodulatory and anti-inflammatory genes known to
      extend the functional viability of pancreatic islet grafts in an autoimmune
      system. These genes, indoleamine 2,3-dioxygenase (IDO), manganese superoxide
      dismutase (MnSOD), and interleukin (IL)-1 receptor antagonist protein (IRAP),
      were transferred to isolated NOD donor islets ex vivo then transplanted to
      NODscid recipients and evaluated in vivo after diabetogenic T-cell challenge. The
      length of time the recipient remained euglycemic was used to measure the ability
      of the transgenes to protect the graft from autoimmune destruction. Although the
      results of these cotransfections gave little evidence of a synergistic
      relationship, they were useful to show that gene combinations can be used to more
      efficiently protect islet grafts from diabetogenic T cells.

PMID- 15512789
TI  - Noninvasive orthogonal polarization spectral imaging as applied to microvascular
      studies in mice.
AB  - In vivo observations of the mouse microcirculation can hardly be performed due to
      technical difficulties, limiting the knowledge that could be obtained from gene
      manipulated mice models. The aim of the present study was to check the
      applicability of a novel optical system, the orthogonal polarization spectral
      technology, to study the mouse microcirculation. In anaesthetized mice, the
      spinotrapezius muscle microcirculation was observed in situ. The diameter of
      precapillary arterioles was measured before and after a pharmacological or
      hormonal stimulation. High-contrast images of the muscle microcirculation were
      obtained and significant vasodilatation of arterioles was observed after topical
      applications of acetylcholine, sodium nitroprusside, and insulin. As compared to
      conventional techniques, orthogonal polarization spectral imaging makes it
      possible to assess and study microvascular beds in mice, which were inaccessible
      until now, allowing the use of gene manipulated mice to investigate, for example,
      the mechanisms involved in the development of diabetic microangiopathy.

PMID- 15512790
TI  - Improved experimental procedures for achieving efficient germ line transmission
      of nonobese diabetic (NOD)-derived embryonic stem cells.
AB  - The manipulation of a specific gene in NOD mice, the best animal model for
      insulin-dependent diabetes mellitus (IDDM), must allow for the precise
      characterization of the functional involvement of its encoded molecule in the
      pathogenesis of the disease. Although this has been attempted by the cross
      breeding of NOD mice with many gene knockout mice originally created on the 129
      or C57BL/6 strain background, the interpretation of the resulting phenotype(s)
      has often been confusing due to the possibility of a known or unknown disease
      susceptibility locus (e.g., Idd locus) cosegregating with the targeted gene from
      the diabetes-resistant strain. Therefore, it is important to generate mutant mice
      on a pure NOD background by using NOD-derived embryonic stem (ES) cells. By using
      the NOD ES cell line established by Nagafuchi and colleagues in 1999 (FEBS Lett.,
      455, 101-104), the authors reexamined various conditions in the context of cell
      culture, DNA transfection, and blastocyst injection, and achieved a markedly
      improved transmission efficiency of these NOD ES cells into the mouse germ line.
      These modifications will enable gene targeting on a "pure" NOD background with
      high efficiency, and contribute to clarifying the physiological roles of a
      variety of genes in the disease course of IDDM.

PMID- 15512791
TI  - Effect of high glucose concentration on collagen synthesis and cholesterol level
      in the phenotypic modulation of aortic cultured smooth muscle cells of sand rat
      (Psammomys obesus).
AB  - To simulate diabetic conditions, the effects of high glucose concentration on
      collagen synthesis and cholesterol level in cultured aortic smooth muscle cells
      of Psammomys were investigated. For collagen biosynthesis, smooth muscle cells
      (SMCs) were incubated in synthetic proliferative phase and in postconfluent phase
      with 3H-proline. Cellular cholesterol was determined by enzymatic method. Under
      high glucose concentration, the results showed morphological modifications
      characterized by morphometric cellular, nuclear, and nucleolar changes. In
      biochemical studies, the authors observed an increase of free and esterified
      cellular cholesterol as well as of total proteins, collagen biosynthesis, and
      alpha1 (I+III) and alpha2 (I) chains of collagen contained in the SMCs and in the
      extracellular matrix. These results showed the sensitivity of Psammomys aortic
      SMCs to high glucose concentration and would constitute an interesting cellular
      model to study atherosclerosis pathogeny in experimental diabetes.

PMID- 15512792
TI  - Commentary: DNA base excision repair defects in human pathologies.
AB  - DNA base excision repair (BER) is the main pathway for repair of endogenous
      damage in human cells. It was expected that a number of degenerative diseases
      could derive from BER defects. On the contrary, the link between BER defects and
      human pathology is elusive and the literature is full of conflicting results. The
      fact that most studies have investigated DNA variations but not their functional
      consequences has probably contributed to this confusing picture. From a
      functional point of view, it is likely that gross BER defects are simply not
      compatible with life and only limited reductions can be observed. Notwithstanding
      those limits, the pathological consequences of partial BER defects might be
      widespread and significant at the population level. This starts to emerge in
      particular for colorectal and lung cancer.

PMID- 15512793
TI  - Peroxyl-oxidized erythrocyte membrane band 3 protein with anion transport
      capacity is degraded by membrane-bound proteinase.
AB  - Human red blood cells anion exchange protein (band 3) exposed to peroxyl radicals
      produced by thermolysis of 2,2'-azo-bis(2-amidinopropane) (AAPH) is degraded by
      proteinases that prevent accumulation of oxidatively damaged proteins. To assess
      whether this degradation affects anion transport capacity we used the anionic
      fluorescent probe 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-y) amino] ethanosulfonate
      (NBD-taurine). A decrease of band 3 function was observed after exposure to
      peroxyl radicals. In the presence of proteinase inhibitors the decrement of anion
      transport through band 3 was smaller indicating that removal achieved by
      proteinases includes oxidized band 3 which still retain transport ability.
      Proteinases recognize band 3 aggregates produced by peroxyl radicals as was
      evaluated by immunoblotting. It is concluded that decrease of band 3 transport
      capacity may result from a direct protein oxidation and from its degradation by
      proteinases and that band 3 aggregates removal may prevent macrophage recognition
      of the senescent condition which would lead to cell disposal.

PMID- 15512794
TI  - Spinnokinetic analyses of blood disposition and biliary excretion of nitric oxide
      (NO)-Fe(II)-N-(dithiocarboxy)sarcosine complex in rats: BCM-ESR and BEM-ESR
      studies.
AB  - Nitric oxide (NO) is well known to have a wide variety of biological and
      physiological functions in animals. On the basis of the fact that Fe(II)
      dithiocarbamates react with NO, a Fe(II)-N-(dithiocarboxy)sarcosine complex
      (Fe(II)-DTCS) was proposed as a trapping agent for endogenous NO. However,
      quantitative pharmacokinetic investigation for NO-Fe(II)-dithiocarbamate
      complexes in experimental animals has been quite limited. This paper describes
      the results on the quantitative pharmacokinetic features of a NO-Fe(II)-N-DTCS in
      both the blood and bile of rats following intravenous (i.v.) administration of
      the complex. For this purpose, we applied two in vivo methods, i.e. (1) in vivo
      blood circulation monitoring-electron spin resonance (BCM-ESR) which previously
      developed, and (2) in vivo biliary excretion monitoring-electron spin resonance
      (BEM-ESR). We monitored real-time ESR signals due to nitrosyl-iron species in the
      circulating blood and bile flow. The ESR signal due to NO-Fe(II)-DTCS was stable
      in biological systems such as the fresh blood and bile. In in vivo BCM- and BEM
      ESR, the pharmacokinetic parameters were calculated on the basis of the two
      compartment and hepatobiliary transport models. The studies also revealed that
      the compound is widely distributed in the peripheral organs and partially
      excreted into the bile. We named a kinetic method to follow spin concentrations
      as spinnokinetics and this method will be useful for detecting and quantifying
      the endogenously generated NO in Fe(II)-DTCS administered animals.

PMID- 15512795
TI  - Hypericin and photodynamic treatment do not interfere with transport of vitamin C
      during respiratory burst.
AB  - Hypericin is a photosensitizing pigment found in St. John's wort (Hypericum
      perforatum) displaying a high toxicity towards certain tumors. The fact that some
      non-tumor cells, especially monocytes and granulocytes, are resistant to its
      photocytotoxic effects, posed the question whether this insensitivity is due to
      their ability to accumulate vitamin C, an antioxidant which alleviates the
      deleterious work of free radicals. HL-60 promyelocytic tumor cells can be
      differentiated to neutrophilic granulocytes by treatment with dimethylsulfoxide
      and were used as cell model. In the differentiated cells, treatment with phorbol
      esters (PMA) stimulates vitamin C (ascorbate) transport. The uptake rates were
      unaltered by hypericin at concentrations below 1 microM and irradiation with
      visible light at a light dose of 6 J/cm2. Inhibition by higher concentrations of
      hypericin was most probably due to a combination of photocytotoxic properties of
      the dye and oxygen radicals generated during respiratory burst. Superoxide
      production by NADPH oxidase followed by reduction of ferricytochrome c was
      inhibited by hypericin. The degree of inhibition was dependent on the
      concentration of hypericin and light intensity: IC50-values were 1.7 and 0.7
      microM under light doses of 3.6 and 10.8 J/cm2, respectively. Oxidative stress,
      monitored with 2',7'-dichlorofluorescein (DCF) was only slightly decreased by
      ascorbate even at higher concentrations of hypericin. In contrast to its effect
      on the ferricytochrome c-reduction, irradiation had no significant influence on
      DCF-fluorescence. However, the viability of the cells was strongly decreased
      after photosensitization and no significant improvement was obtained by
      ascorbate. Results from this work indicate that ascorbate transport per se is not
      altered during photodynamic therapy and vitamin C does not interfere with
      hypericin-induced photodamage of cellular targets.

PMID- 15512796
TI  - R-lipoic acid inhibits mammalian pyruvate dehydrogenase kinase.
AB  - The four pyruvate dehydrogenase kinase (PDK) and two pyruvate dehydrogenase
      phosphatase (PDP) isoenzymes that are present in mammalian tissues regulate
      activity of the pyruvate dehydrogenase complex (PDC) by
      phosphorylation/dephosphorylation of its pyruvate dehydrogenase (E1) component.
      The effect of lipoic acids on the activity of PDKs and PDPs was investigated in
      purified proteins system. R-lipoic acid, S-lipoic acid and R-dihydrolipoic acid
      did not significantly affect activities of PDPs and at the same time inhibited
      PDKs to different extents (PDK1>PDK4 approximately PDK2>PDK3 for R-LA). Since
      lipoic acids inhibited PDKs activity both when reconstituted in PDC and in the
      presence of E1 alone, dissociation of PDK from the lipoyl domains of
      dihydrolipoamide acetyltransferase in the presence of lipoic acids is not a
      likely explanation for inhibition. The activity of PDK1 towards phosphorylation
      sites 1, 2 and 3 of E1 was decreased to the same extent in the presence of R
      lipoic acid, thus excluding protection of the E1 active site by lipoic acid from
      phosphorylation. R-lipoic acid inhibited autophosphorylation of PDK2 indicating
      that it exerted its effect on PDKs directly. Inhibition of PDK1 by R-lipoic acid
      was not altered by ADP but was decreased in the presence of pyruvate which itself
      inhibits PDKs. An inhibitory effect of lipoic acid on PDKs would result in less
      phosphorylation of E1 and hence increased PDC activity. This finding provides a
      possible mechanism for a glucose (and lactate) lowering effect of R-lipoic acid
      in diabetic subjects.

PMID- 15512797
TI  - Effects of hemodialysis, dialyser type and iron infusion on oxidative stress in
      uremic patients.
AB  - Uremic patients undergoing hemodialysis (HD) are considered to face an elevated
      risk for atherosclerosis and cancer. This has been attributed in part to an
      increased oxidative stress. In this pilot study, oxidative cell damage in blood
      of HD-patients was compared to those of controls: total DNA damage (basic and
      specific oxidative DNA damage), modulation of glutathione levels (total and
      oxidized glutathione) and of lipid peroxidation were monitored via the Comet
      assay (with and without FPG), a kinetic photometric assay and HPLC quantification
      of plasma malondialdehyde (MDA), respectively. In some samples, leukocytes were
      analysed for malondialdehyde-deoxyguanosine-adducts (M1dG) with an immunoslot
      blot technique. HD-patients (n=21) showed a significant increase of total DNA
      damage (p<10(-12)), compared to controls (n=12). In a subset of patients and
      controls, GSSG levels and M1dG, however, only increased slightly, while tGSH and
      MDA levels did not differ. The influence of different low flux HD-membranes was
      tested in a pilot study with nine patients consecutively dialysed on three
      membrane types for four weeks each. In addition to the individual disposition of
      the patient, the dialyser membrane had a significant impact on oxidative stress.
      Total DNA damage was found to be almost identical for polysulfone and vitamin E
      coated cellulosic membranes, whereas a slight, but significant increase was
      observed with cellulose-diacetate (p<0.001). In patients receiving iron infusion
      during HD, MDA-formation (n=11) and total DNA damage (n=10) were additionally
      increased (p<0.005). Our results show an increased oxidative damage in HD
      patients, compared to healthy volunteers. Significant influences were found for
      the dialyser membrane type and iron infusion.

PMID- 15512798
TI  - Interference of plasmatic reduced glutathione and hemolysis on glutathione
      disulfide levels in human blood.
AB  - The blood reduced glutathione (GSH)/GSH disulfide (GSSG) ratio is an index of the
      oxidant/antioxidant balance of the whole body. Nevertheless, data indicating GSH
      and GSSG physiological levels are still widely divergent, especially those on
      GSSG, probably due to its low concentration. Standardization in methodological
      protocols and sample manipulation could help to minimize these discrepancies.
      Therefore, we have investigated how plasma reduced GSH, which is rapidly oxidized
      after blood withdrawal, could alter the blood GSSG measurement if the sample is
      not suitably processed. We have observed that an increase in plasma GSH
      concentration, due to red blood cell hemolysis, is responsible for a significant
      overestimation of blood GSSG level. Our results show that, before performing
      blood GSSG determination, thiols have to be rapidly blocked, to avoid possible
      pitfalls in GSSG measurement, in particular when hemolysis is present.

PMID- 15512799
TI  - Quinone-enhanced ascorbate reduction of nitric oxide: role of quinone redox
      potential.
AB  - The quinones 1,4-naphthoquinone (NQ), methyl-1,4-naphthoquinone (MNQ), trimethyl
      1,4-benzoquinone (TMQ) and 2,3-dimethoxy-5-methyl-1,4-benzoquinone (UQ-0) enhance
      the rate of nitric oxide (NO) reduction by ascorbate in nitrogen-saturated
      phosphate buffer (pH 7.4). The observed rate constants for this reaction were
      determined to be 16+/-2,215+/-6,290+/-14 and 462+/-18 M-1 s-1, for MNQ, TMQ, NQ
      and UQ-0, respectively. These rate constants increase with an increase in quinone
      one-electron redox potential at neutral pH, E1(7). Since NO production is
      enhanced under hypoxia and under certain pathological conditions, the
      observations obtained in this work are very relevant to such conditions.

PMID- 15512800
TI  - Phosphate increases mitochondrial reactive oxygen species release.
AB  - The effects of inorganic phosphate (Pi), the main intracellular membrane
      permeable anion capable of altering mitochondrial pH gradients (Delta pH), were
      measured on mitochondrial H2O2 release. As expected, Pi decreased Delta pH and
      increased the electric membrane potential (Delta Psi). Mitochondrial H2O2 release
      was stimulated by Pi and also by its structural analogue arsenate. However,
      acetate, another membrane-permeable anion, did not stimulate mitochondrial H2O2
      release. The stimulatory effect promoted by Pi was prevented by CCCP, which
      decreases transport of Pi across the inner mitochondrial membrane, indicating
      that Pi must be in the mitochondrial matrix to stimulate H2O2 release. In
      conclusion, we found that Pi and arsenate stimulate mitochondrial reactive oxygen
      release, an effect that may contribute towards oxidative stress under conditions
      such as ischemia/reperfusion, in which high-energy phosphate bonds are
      hydrolyzed.

PMID- 15512801
TI  - Overexpression of manganese superoxide dismutase promotes the survival of
      prostate cancer cells exposed to hyperthermia.
AB  - It has been hypothesized that exposure of cells to hyperthermia results in an
      increased flux of reactive oxygen species (ROS), primarily superoxide anion
      radicals, and that increasing antioxidant enzyme levels will result in protection
      of cells from the toxicity of these ROS. In this study, the prostate cancer cell
      line, PC-3, and its manganese superoxide dismutase (MnSOD)-overexpressing clones
      were subjected to hyperthermia (43 degrees C, 1 h). Increased expression of MnSOD
      increased the mitochondrial membrane potential (MMP). Hyperthermic exposure of PC
      3 cells resulted in increased ROS production, as determined by aconitase
      inactivation, lipid peroxidation, and H2O2 formation with a reduction in cell
      survival. In contrast, PC-3 cells overexpressing MnSOD had less ROS production,
      less lipid peroxidation, and greater cell survival compared to PC-3 Wt cells.
      Since MnSOD removes superoxide, these results suggest that superoxide free
      radical or its reaction products are responsible for part of the cytotoxicity
      associated with hyperthermia and that MnSOD can reduce cellular injury and
      thereby enhance heat tolerance.

PMID- 15512802
TI  - Secretion of ferritin by iron-laden macrophages and influence of lipoproteins.
AB  - Increasing evidence supports a role of cellular iron in the initiation and
      development of atherosclerosis. We and others reported earlier that iron-laden
      macrophages are associated with LDL oxidation, angiogenesis, nitric oxide
      production and apoptosis in atherosclerotic processes. Here we have further
      studied perturbed iron metabolism in macrophages, their interaction with
      lipoproteins and the origin of iron accumulation in human atheroma. In both early
      and advanced human atheroma lesions, hemoglobin and ferritin accumulation
      correlated with the macrophage-rich areas. Iron uptake into macrophages, via
      transferrin receptors or scavenger receptor-mediated erythrophagocytosis,
      increased cellular iron and accelerated ferritin synthesis at both mRNA and
      protein levels. The binding activity of iron regulatory proteins was enhanced by
      desferrioxamine (DFO) and decreased by hemin and iron compounds. Iron-laden
      macrophages exocytosed both iron and ferritin into the culture medium. Exposure
      to oxidized low-density lipoprotein (oxLDL, >or=50 microg/mL) resulted in <20%
      apoptosis of iron-laden human macrophages, but cells remained impermeable after a
      24 h period and an increased excretion of ferritin could be observed by
      immunostaining techniques. Exposure to high-density lipoprotein (HDL)
      significantly decreased ferritin excretion from these cells. We conclude: (i)
      erythrophagocytosis and hemoglobin catabolism by macrophages contribute to
      ferritin accumulation in human atherosclerotic lesions and; (ii) iron uptake into
      macrophages leads to increased synthesis and secretion of ferritin; (iii)
      oxidized LDL and HDL have different effects on these processes.

PMID- 15512805
TI  - Signalling pathways activated by all-trans-retinoic acid in acute promyelocytic
      leukemia cells.
AB  - Acute promyelocytic leukemia is a form of acute myelogenous leukemia,
      characterized by the t(15;17) chromososmal translocation and the presence of the
      abnormal PML-RARalpha fusion protein. All-trans-retinoic acid is a potent agent
      for the treatment of this fatal subtype of AML, and is particularly effective
      when combined with cytotoxic chemotherapy. The important biological activities of
      all-trans-retinoic acid in vitro and in vivo have provoked extensive studies over
      the years, aimed to define the mechanisms by which it induces its antileukemic
      effects. It is now well established that all-trans-retinoic acid when
      administered at pharmacological doses can reverse the dominant-negative effects
      that the PML-RARalpha oncoprotein exhibits on the functions of the wild type PML
      and RARalpha proteins. All-trans-retinoic acid induces gene transcription via
      retinoic acid responsive elements (RARE) that are present in the promoters of
      retinoid-responsive genes that ultimately result in the production of protein
      products that regulate leukemic cell differentiation and induce cell-cycle
      arrest. There is now accumulating evidence that additional signalling pathways
      are activated during all-trans-retinoic acid-treatment of cells, involving Stat
      proteins, tyrosine kinases and mitogen-activated protein (Map) kinases. This
      review summarizes the current knowledge on the signalling cascades activated by
      all-trans-retinoic acid in APL cells. The clinical implications and potential
      translational applications from the accumulating knowledge in the field are also
      discussed.

PMID- 15512806
TI  - Clinical activity of farnesyl transferase inhibitors in hematologic malignancies:
      possible mechanisms of action.
AB  - Farnesyl transferase inhibitors (FTIs) are a novel class of anti-cancer agents
      that competitively inhibit farnesyl protein transferase (FTase). Initially
      developed to inhibit the prenylation necessary for Ras activation, their
      mechanism of action seems to be more complex, involving other proteins unrelated
      to Ras. FTIs have been developed and tested across a wide range of human cancers.
      At least 3 agents within this family have been investigated in hematologic
      malignancies. These are tipifarnib (R115777, Zarnestra), lonafarnib (SCH66336,
      Sarasar), both of which are orally administered, and BMS-214662, which is given
      intravenously. Preliminary results from clinical trials demonstrate enzyme target
      inhibition, a favorable toxicity profile and promising efficacy. Ongoing studies
      will better determine their mechanism of action and the role of combination with
      other agents, defining their place in the therapeutic arsenal of hematologic
      disorders.

PMID- 15512807
TI  - Clonal cytogenetic abnormalities in Philadelphia chromosome negative cells in
      chronic myeloid leukemia patients treated with imatinib.
AB  - Treatment of chronic myeloid leukemia (CML) with imatinib (Gleevec) induces a
      much higher rate of partial and complete cytogenetic responses (CCR) than
      interferon-alpha (IFN)-based therapies. Conventional wisdom suggests that
      elimination of the Philadelphia (Ph)- positive cells will lead to re
      establishment of normal Ph-negative hematopoiesis. Surprisingly, karyotypic
      abnormalities were detected in the chromosome negative cells of some patients
      with cytogenetic response to imatinib. In some cases, this was associated with a
      myelodysplastic syndrome (MDS). While clonal evolution in Ph-positive cells is
      considered part of the progression of CML, clonal evolution in Ph-negative cells
      had been observed only rarely in a small number of patients treated with IFN or
      bone marrow transplantation, raising the question whether the phenomenon may be
      causally linked to imatinib therapy. In this manuscript, we will review the
      currently available data, suggest possible causes and discuss potential
      implications for patient management. We are fully aware that a systematic study
      of a larger patient cohort will be required to conclusively address these issues.

PMID- 15512808
TI  - PECAM-1, apoptosis and CD34+ precursors.
AB  - Apoptosis is a physiological process that controls tissue homeostasis, in
      combination with survival signals delivered by distinct receptors that bind
      hormones, growth factors or extracellular matrix components. The extrinsic
      pathway of apoptosis is due to the triggering of death receptors and the
      activation of the caspase cascade; the intrinsic pathway is due to withdrawal of
      growth factors and mainly related to mitochondrial metabolism. The choice between
      survival or apoptosis, which is the result of such different integrated
      environmental signals, is crucial for the maintainance of bone marrow reservoir
      of hematopoietic precursors (HPC). CD34+ HPC can receive multiple survival
      signals during homing and maturation, due to different interactions with adhesion
      molecules expressed on endothelial and bone marrow stromal cells, proteins of the
      extracellular matrix and chemokines or growth factors. Among them, the signal
      delivered via platelet endothelial cell adhesion molecule-1 (PECAM-1) seems to
      contribute to the resistance of this cell population to starvation, and it is
      related to the maintainance of mitochondrial metabolism. Indeed, this molecule,
      originally described as an adhesion receptor belonging to the immunoglobulin
      superfamily, capable of homophilic and heterophilic interactions, turned out to
      be a signalling molecule, containing an immunoreceptor tyrosine-based inhibitory
      motifs (ITIM) within its cytoplasmic domain. In particular, it has been shown
      that PECAM-1 binds to different kinases and phosphatases, including the
      phosphatidylinositide-3-kinase that phosphorylates Akt, which, in turn can
      upregulate transcription and function of antiapoptotic proteins, such as Bcl-2
      and Bcl-x or A1, responsible for the rescue from mitochondrial apoptosis. The
      possible role of PECAM-1 engagement in the prevention of starvation-induced
      apoptosis of HPC precursors and in the maintainance of their survival is
      discussed.

PMID- 15512810
TI  - Comparison of two functional flow cytometric assays to assess P-gp activity in
      acute leukemia.
AB  - One of the possible causes of treatment failure in acute leukemia is the
      emergence of multidrug resistance caused by P-glycoprotein (P-gp) overexpression.
      We compared a flow cytometric assay using JC-1 with a technique using rhodamine
      123 (rho123) to evaluate the P-gp function in acute leukemia. Samples from 50
      acute leukemia patients were analyzed by both functional assays. The P-gp
      expression was assessed by an immunological flow cytometric test and the
      association between the P-gp status and the clinical outcome was evaluated. Of
      all samples, 28% showed a reversible JC-1 efflux and 36% scored positive for the
      rho123 assay. In two cases, the leukemic blasts showed a reversible JC-1 efflux
      whereas they were negative for rho123. These patients had blast cells with a very
      low P-gp activity. Six samples scored positive for the rho123 assay but were
      negative for the JC-1 test. Five of these samples did not express P-glycoprotein
      and were considered false positive. We found a strong correlation between the JC
      1 and the rho123 test (R(s)=0.59, p<0.0001) and the JC-1 and the immunological
      assay (R(s)=0.29, P=0.05). There was also an association between the JC-1 status
      and the clinical outcome of adult patients (chi2=6.30, P=0.04). In conclusion, we
      recommend the JC-1 assay to study the P-gp activity in acute leukemia because it
      is more specific and less labor intensive than conventional functional flow
      cytometric tests using rhodamine 123. In addition, the JC-1 assay can be used to
      identify adult patients with an increased risk for adverse clinical outcome.

PMID- 15512809
TI  - Oral valacyclovir as prophylaxis against herpes simplex virus reactivation during
      high dose chemotherapy for leukemia.
AB  - Reactivation of herpes simplex virus is a common event in patients undergoing
      dose-intensive remission induction or consolidation chemotherapy of acute
      leukemia, for which either intravenous or oral acyclovir provides effective
      prophylaxis. This drug's short serum half-life and low oral bioavailability make
      frequent dosing necessary, however, and we therefore sought to determine if the
      pro-drug valacyclovir, which has improved bioavailability, could be successfully
      substituted for this indication. Eighty-one patients with leukemia were
      randomized to receive either 500 mg or 1,000 mg of valacyclovir orally every 8 h
      and followed clinically, as well as with serial surveillance cultures. Over a
      total of 1,979 days on study between the groups, and 380 throat cultures, no
      documented episodes of herpes simplex reactivation were noted. Valacyclovir was
      tolerated well with no evident drug-related toxicities. We conclude that
      valacyclovir at either of the two doses studied can be safely substituted for
      oral or intravenous acyclovir, and that it provides effective prophylaxis against
      reactivation of herpes simplex virus in this patient population.

PMID- 15512811
TI  - Survivin expression in acute leukemias and myelodysplastic syndromes.
AB  - We analyzed by immunocytochemistry the expression of survivin in bone marrow
      cells from 36 acute myeloid leukemia (AML) cases, from 98 patients with
      myelodysplastic syndrome (MDS), and from 41 non hemopathic subjects. Our aim was
      to evaluate whether abnormalites in survivin expression were associated with
      peculiar laboratory and clinical findings, altered apoptosis levels or altered
      proliferative rate. In normal samples survivin was never detectable. It was
      detected in almost all AML and MDS cases. In AML and in MDS with more than 5%
      bone marrow blasts survivin levels higher than in RA and RARS were observed
      (P=0.04). In MDS a tendential inverse correlation between survivin and TUNEL
      positivity was identified (P=0.08), whereas survivin expression was independent
      of the proliferative rate. Survivin levels did not predict disease progression in
      MDS; among AML patients treated with intensive polichemotherapy, survivin
      expression was significantly higher in resistant cases (P=0.01). Our findings
      confirm the high incidence of survivin expression in AML. Its abnormal expression
      also in MDS may play a role in promoting aberrantly increased cell viability and
      contribute to the altered homeostatic balance between cell growth and cell death.

PMID- 15512812
TI  - Fludarabine in comparison to alkylator-based regimen as induction therapy for
      chronic lymphocytic leukemia: a systematic review and meta-analysis.
AB  - The superiority of Fludarabine over conventional therapy as primary induction
      therapy for patients with chronic lymphocytic leukemia (CLL) has been shown in
      several studies but no studies have yet reported a pooled estimate of the
      treatment effect. We performed a systematic review of evidence from 5 randomized
      controlled trials involving approximately 1300 patients with CLL, comparing
      Fludarabine with several alkylator-based combination regimens in the primary
      treatment of CLL. Complete response rate was significantly higher for Fludarabine
      compared to alkylator-based chemotherapy (RR 1.87, 95% CI 1.10-3.19, P=0.02),
      while overall response, though superior, did not reach statistical significance
      (RR 1.22, 95% CI=0.88-1.69, P=0.24). Overall survival was similar for Fludarabine
      and alkylator-based therapy (the pooled log hazard ratio of death, HR=-0.05, 95%
      CI=-0.36-0.26, P=0.75). Infection rate was significantly higher (RR 1.58, 95%
      CI=1.10-2.27, P=0.01), but there was no significant difference in the incidence
      of thrombocytopenia, neutropenia and anemia. Therefore, this meta-analysis
      supports the findings that Fludarabine as an induction agent for patients with
      CLL yields a better clinical response with acceptable toxicity when compared with
      alkylator-based combination therapy, but without a survival benefit by 5-6 years
      of follow up.

PMID- 15512813
TI  - Interferon alpha 2b as maintenance therapy improves outcome in follicular
      lymphoma.
AB  - The role of interferon alpha as maintenance therapy in follicular lymphoma (FL)
      remains unsolved. We started a controlled clinical trial to assess if interferon
      alpha 2b could improve outcome, measured with event free survival (EFS) and
      overall survival (OS) in patients with FL in complete remission after
      chemotherapy based anthracyclines and adjuvant radiotherapy to sites of initial
      bulky disease. Three hundred and eighty four patients in complete response after
      6 cycles of CEOP-Bleo (cyclophosphamide, epirubicin, vincristine, prednisone and
      bleomycin, at standard doses), and adjuvant radiotherapy when necessary, were
      randomized to received Interferon alpha 2b, three times a week for 1 year or no
      treatment (control group). Median follow up was 9.8 years (range 7.0-15 years);
      actuarial curves showed that EFS was 64% (95% confidence interval (CI) 56-71%) in
      patients treated with interferon that was statistically significant to patients
      in the control group: 35% (95% CI: 28-43%) (p<.01). OS was also statistically
      significant: 81% in patients treated with interferon (95% CI: 74-93%) and 57%
      (95% CI: 50-63%) in the control group (p<.001). Toxicity was mild, all patients
      received the planned dose of interferon on time. The use of aggressive
      chemotherapy and maintenance therapy with interferon alpha 2b in follicular
      lymphoma improved outcome; more than 60% of patients remain alive free of disease
      at longer follow-up.

PMID- 15512814
TI  - High dose chemotherapy with thiotepa, mitoxantrone and carboplatin (TMJ) followed
      by autologous stem cell support in 100 consecutive lymphoma patients in a single
      centre: analysis of efficacy, toxicity and prognostic factors.
AB  - High dose chemotherapy with autologous stem cell transplant is often used in
      patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) who either
      do not respond to, or relapse after conventional chemotherapy. There is no
      consensus on the "ideal" pretransplant conditioning regimen. In this study, we
      analyzed the results of 100 consecutive patients with HD and NHL who met our
      eligibility criteria and underwent autologous stem cell transplant at New York
      Medical College and Zalmen A. Arlin Cancer Institute. All patients received high
      dose chemotherapy with thiotepa, mitoxantrone and carboplatin (TMJ). One hundred
      patients, 37 with HD and 63 with NHL underwent autologous stem cell transplant
      using TMJ as a conditioning regimen. All patients with HD had chemo-sensitive
      relapse while 50 patients with NHL had chemo-sensitive relapse and 13 patients
      had first complete remission. The source of stem cells was bone marrow (18
      patients), peripheral blood (50 patients) and both bone marrow and peripheral
      blood (32 patients). With a median follow up of 91 months (range 23-147 months),
      the median survival of patients with HD and NHL who underwent autologous stem
      cell transplant is 107 months and the 5 years disease free survival is 43%.
      Median survival of patients with HD and NHL is 87 and 107 months respectively.
      There were 4 transplant related deaths. Median survival of patients who had
      sensitive relapse at the time of transplant is 87 months while median survival
      has not been reached for patients who had first complete remission at the time of
      transplant. Multivariate analysis identified age>35 years (P=0.02) as a predictor
      for poor survival for the whole group as well as for patients with NHL (P=0.04).
      TMJ is a safe and effective regimen when used as a part of autologous stem cell
      transplant for patients with HD and NHL.

PMID- 15512815
TI  - Histology impacts the outcome of peripheral T-cell lymphomas after high dose
      chemotherapy and stem cell transplant.
AB  - The role of high dose chemotherapy (HDC) and stem cell transplant (SCT) in
      peripheral T-cell lymphoma (PTCL) was studied in 28 patients, from 1988 to 2002.
      The aim was to determine if subsets recognized by the REAL/WHO classification
      have different prognoses. Outcome was compared to 86 patients with diffuse large
      B-cell lymphoma (DLBCL) transplanted during 1986-2000. The 3-year overall
      survival (OS) and event free survival (EFS) were 69% and 50%. Patients with
      anaplastic large cell lymphoma (ALCL) had a better 3-year OS compared to those
      with non-ALCL histology (86% vs. 47%, P=0.0122). Anaplastic lymphoma kinase (ALK)
      positive ALCL patients had a superior EFS compared to ALK-negative ALCL (100%
      vs. 0; P=0.0228). Patients with cutaneous ALCL (ALK-negative) relapsed, but had
      an indolent course after SCT. Low International Prognostic Index score at relapse
      predicted for a better 3-year OS (85% vs. 34%, P=0.0238). When compared to DLBCL,
      patients with ALCL had a superior OS (86% vs. 36%, P=0.0034) and patients with
      non-ALCL had a comparable OS. ALCL histology confers better survival compared to
      non-ALCL and DLBCL histologies. ALK-positive ALCL is associated with the best EFS
      after relapse with HDC and SCT. The timing of SCT for non-ALCL histology remains
      to be determined.

PMID- 15512816
TI  - A pilot trial of rituximab and alemtuzumab combination therapy in patients with
      relapsed and/or refractory chronic lymphocytic leukemia (CLL).
AB  - The treatment of patients with chronic lymphocytic leukemia (CLL) who fail purine
      analogues is sub optimal. CLL lymphocytes express two antigens, namely CD 20 and
      CD 52, for which monoclonal antibodies are readily available. Rituximab is a
      chimeric monoclonal antibody targeted against CD 20, which has some activity in
      refractory CLL, with primary effect on nodal disease. Alemtuzumab is a humanized
      anti-CD 52 antibody that is approved for the treatment of CLL in patients who
      fail alkylating agents and purine analogues. Alemtuzumab has better activity in
      the peripheral blood and the bone marrow compared to nodal disease. We
      investigated whether combining both antibodies is safe in refractory CLL. Both
      antibodies were given to a total of 12 patients divided into 3 cohorts with
      escalating alemtuzumab doses (3 mg, 10 mg, and 30 mg). The combination was proven
      to be safe, not toxic, feasible, and active. One patient attained PR by NCI
      criteria while all other patients had stable disease lasting a median of 101.5
      days. All patients normalized their peripheral lymphocytosis within a median of
      23.5 days. No treatment-related mortality was identified. No CMV reactivation
      occurred. Additional studies are needed to investigate the clinical significance
      of such a combination in this patient population, and whether this combination
      can be administered safely with systemic chemotherapy. These studies are
      currently underway.

PMID- 15512817
TI  - Treatment of relapsed/refractory multiple myeloma with thalidomide-based
      regimens: identification of prognostic factors.
AB  - We evaluated the predictive value of several parameters, including the
      International Staging System (ISS) for myeloma, in patients with advanced disease
      treated with thalidomide-based regimens (TBR). We analyzed 119 patients, from 3
      phase II studies. Patients with pretreatment beta2 microglobulin<3.5 mg/l and
      albumin 3.5 g/dl were scored ISS stage 1, patients with beta2 microglobulin<3.5
      mg/l and albumin<3.5 g/dl or beta2 microglobulin 3.5-5.5 mg/l regardless of
      albumin levels were scored ISS stage 2, patients with beta2 microglobulin>5.5
      mg/l ISS stage 3. ISS stage was 1, 2 and 3 in 45, 32 and 23% of patients
      respectively. Seventy-four patients (62%) achieved at least partial response.
      Median progression-free and overall survival were 8 months and 19.5 months
      respectively. ISS stage, serum LDH and performance status were independent
      predictive factors for survival. Based on these 3 variables a scoring system was
      developed with survival times of 38.1, 28.8 and 5.8 months for scores 0, 1 and 2
      respectively. The ISS staging system was highly predictive for overall survival
      of patients with advanced myeloma treated with TBR. With the addition of
      performance status and serum LDH, a simple scoring system was developed which may
      help select patients likely to benefit from TBR.

PMID- 15512818
TI  - C-kit receptor (CD117) expression on plasma cells in monoclonal gammopathies.
AB  - The surface expression of CD117 antigen (c-kit) on plasma cells from 158 multiple
      myeloma (MM), 12 plasma cell leukemia (PCL), 7 MGUS, 7 IgM lymphoplasmacytic
      lymphoma patients and 10 healthy subjects has been analyzed by flow cytometry
      using triple staining with the monoclonal antibodies CD138, CD117 and CD38. The
      antigen expression intensity was calculated as relative fluorescence intensity
      (RFI) and for direct quantitative analysis the QuantiBRITE test (Becton
      Dickinson) was applied. Antibody bounding capacity (ABC) was calculated using
      QuantiCALC software. CD117 antigen was present in 49/158 MM, 5/12 PCL and 5/7
      MGUS patients. The RFI values ranged from 0.2 to 20.2 in particular MM patients
      (mean: 11.0+/-5.3; median 11.5) while the number of CD117 binding sites (ABC) on
      MM plasma cells ranged from 637 to 6217 (mean: 3029+/-1568; median 2946)
      (r=0.8328). In responsive to chemotherapy c-kit positive MM patients the
      percentage of CD117+ plasma cells in the bone marrow decreased significantly
      while in c-kit negative MM patients the percentage of CD117+ cells in bone marrow
      did not change and remained in the normal limits. When comparing the clinical and
      biological disease characteristics (monoclonal protein isotype, albumin, beta2
      microglobulin, lactate dehydrogenase, stage of disease, response to chemotherapy,
      survival time) of c-kit positive and c-kit negative cases, no significant
      differences were found. In CD117 positive PCL cases expression of CD117 was
      detected in bone marrow plasma cells as well as in peripheral blood plasma cells.
      Normal plasma cells and those in IgM lymphoplasmacytic lymphoma did not show
      reactivity for the CD117 antigen. We conclude that it may be rationale to
      consider usefulness of therapy with tyrosine kinase inhibitors in the management
      of c-kit positive plasma cell proliferations. In one third of MM and PCL patients
      c-kit antigen could be considered as a "tumor associated marker" and together
      with CD38 and CD138 it may be of value for the identification of the malignant
      clone in minimal residual disease as it was first suggested by Spanish authors.

PMID- 15512819
TI  - Marked elevation of soluble fas ligand and cytokine secretion after splenectomy
      in aggressive natural killer cell leukemia/lymphoma.
AB  - We report a case of Epstein-Barr virus-associated aggressive natural killer cell
      leukemia/lymphoma with giant splenomegaly in which splenectomy resulted in
      progression of apoptosis and hemophagocytosis. The serum level of ferritin,
      triglycerides, interferon-gamma (IFN-gamma), interleukin 10 (IL-10), and soluble
      Fas ligand (sFasL) increased markedly, and liver damage progressed after
      splenectomy. The number of apoptotic cells in peripheral blood smears increased
      following splenectomy. In the present case, splenectomy caused disruption of the
      cytokine network, resulting in apoptosis of blood cells and hepatocytes, as well
      as phagocytosis.

PMID- 15512820
TI  - Aleukemic mast cell leukemia with abnormal immunophenotype and c-kit mutation
      D816V.
AB  - Mastocytosis comprises a heterogeneous group of disorders characterized by
      proliferation and accumulation of mast cells in 1 or more organ systems. Mast
      cell leukemia (MCL) is an extremely rare subtype of mastocytosis in which a
      leukemic spread of mast cells and a rapid progression of disease is seen. In
      typical cases, mast cells are found in the peripheral blood. However, an
      aleukemic variant of MCL (formerly termed malignant mastocytosis) has also been
      described. We here report a case of aleukemic MCL with abnormal immunophenotype
      of mast cells and the classical c-kit point mutation Asp-816-Val (=D816V). The 75
      year-old male patient had a short history of weight loss and lymphadenopathy.
      There were no urticaria pigmentosa-like skin lesions. The bone marrow was
      diffusely infiltrated with atypical mast cells that comprised more than 80% of
      all nucleated cells on a bone marrow smears. As assessed by immunohistochemistry,
      neoplastic mast cells expressed tryptase, chymase, CD2, CD25, CD68, and the KIT
      protein (CD117). Mutation analysis revealed the c-kit mutation D816V. Since
      circulating mast cells could not be detected in the peripheral blood, the
      diagnosis of aleukemic MCL was established in accordance to the updated WHO
      consensus classification. This case further supports the notion that the
      pathogenesis (c-kit mutation D816V) in MCL is closely related to that found in
      indolent mast cell disorders. However, additional (but yet unknown) molecular
      (genetic) defects have to be considered to explain the extremely heterogenous
      clinical course in these patients.

PMID- 15512821
TI  - A gene homologous to human endogenous retrovirus overexpressed in childhood acute
      lymphoblastic leukemia.
AB  - To clarify the mechanism of progression and acquired drug resistance of leukemia,
      we searched for an overexpressed gene in drug-resistant leukemia cells and
      identified an approximately 5-kb transcript by using the subtraction method. The
      nucleotide sequence of the gene was highly homologous to those of human
      endogenous retrovirus (HERV) transcripts. Reverse transcriptase-polymerase chain
      reaction (RT-PCR) revealed that the gene was overexpressed in cells from 6
      childhood acute lymphoblastic leukemia patients (60%) but not in bone marrow
      cells at remission. Peripheral blood mononuclear cells from normal controls
      (n=11) and bone marrow cells from non-leukemia patients (n=13) did not express
      the gene. These findings indicate that the gene may play a role in leukemogenesis
      and may be a novel leukemia marker. Further studies on the functional role of the
      gene are needed.

PMID- 15512822
TI  - Fludarabine-induced apoptosis in CD19+/CD5+B-CLL cells is a direct and nurse-like
      cell independent effect.
AB  - B-cell chronic lymphocytic leukemia (B-CLL) is a hematological malignancy
      characterized by the accumulation of mature CD5+ B lymphocytes with a defective
      apoptosis. A subset of blood monocyte-derived adherent cells generated in vitro
      protects B-CLL cells from apoptosis playing a role as nurse-like cells (NLCs).
      Fludarabine (9-beta-D-arabinofuranosyl-2-fluoroadenine; F-ara-A) is an adenine
      nucleoside analog used to treat B-CLL. To gain insight into the mechanisms
      implicated in the antitumoral effect of fludarabine in B-CLL cells, we performed
      cross-cultures with B-CLL cells and NLCs treated and untreated with fludarabine.
      Our results showed that fludarabine blocked the development of NLCs and induced
      apoptosis in these cells when they were present in culture. Moreover, CD19+/CD5+B
      CLL cells treated with fludarabine underwent apoptosis and this event was not
      related with the presence of NLCs whether treated or not with fludarabine. In
      conclusion, apoptosis induced by fludarabine in CD19+/CD5+B-CLL cells was due to
      a direct effect on these cells and not due to its effect in the NLCs.

PMID- 15512823
TI  - Expression of interleukin-11 receptor in CD38-positive cells from patients with
      multiple myeloma.
AB  - Interleukin-11, a cytokine with multiple biological activities, has been shown to
      stimulate the proliferation and to support the long-term growth of human myeloma
      cell lines. Despite this, no expression of the interleukin-11alpha receptor has
      so far been demonstrated in myeloma cells. We have investigated the expression of
      interleukin-11alpha receptor and interleukin-11 at the level of mRNA and protein
      product in bone marrow mononuclear cells isolated from patients with multiple
      myeloma using reverse-transcriptase polymerase chain reaction and flow cytometry.
      The mRNA for interleukin-11alpha receptor and/or the corresponding protein were
      identified in 9 of 15 patients with multiple myeloma. In contrast, the
      interleukin-11 was not detected in any of the patients examined.

PMID- 15512824
TI  - Fatal intra-alveolar hemorrhage after rituximab in a patient with non-Hodgkin
      lymphoma.
AB  - A 65-year-old male developed progressive dry cough and digital clubbing after
      starting rituximab-CHOP chemotherapy for non-Hodgkin lymphoma. A lung biopsy
      showed loose non-necrotic granulomas in a background of mild fibrosis and rare
      eosinophils, compatible with a drug-induced hypersensitivity pneumonia.
      Associated manifestations of this hypersensitivity reaction were a high
      eosinophil count, elevated serum levels of immunoglobulin E, and a skin rash
      consistent with pigmented purpuric dermatitis (Schamberg disease).
      Corticosteroids were marginally efficacious in treating this reaction. Few
      similar reactions have since been described, 2 of them ultimately fatal, but none
      was associated with pulmonary hemorrhage. A 2.5:1 ratio between the interstitial
      alveolar T4/T8 lymphocytes in our case is similar to the findings in methotrexate
      induced pneumonitis and farmer lung disease. This report documents the serologic
      and immunohistologic findings associated with a pulmonary interstitial reaction
      to rituximab. A review of the pertinent literature is provided. The possible
      pathogenetic mechanisms, including the role of cytokines, cytotoxic T-lymphocytes
      and CD 20 positive T-cells in relation to the administration of rituximab are
      discussed.

PMID- 15512825
TI  - Follicular non-Hodgkin's lymphoma with refractory paraneoplastic pemphigus: case
      report with review of novel treatment modalities.
AB  - In this paper a patient with a non-Hodgkin's lymphoma (NHL) and paraneoplastic
      pemphigus (PNP) is described. PNP is a very rare, painful mucocutaneous
      intraepithelial blistering disease associated with occult or confirmed
      malignancy. Patients with PNP show severe, progressive mucocutaneous disease with
      a high mortality rate, because of drug-induced infectious complications. The
      patients sometimes benefit from high doses of oral corticosteroids. However,
      pulse therapy with high doses of prednisolone (or dexamethasone) in combination
      with other immunosuppressants induces variable and inconstant results.
      Intravenous immunoglobulin (IVIg) has been applied in different cases of PNP with
      encouraging results. Plasmapheresis or plasma exchange (PE) in combination with
      corticosteroids and/or cyclophosphamide or azathioprine showed similar rapid and
      beneficial results in association with decreasing auto-antibody levels in this
      group of refractory pemphigus. Another interesting therapeutic option is
      rituximab, a chimeric monoclonal antibody directed against the CD20 antigen,
      which is found on the surface of normal and malignant B-lymphocytes.
      Administration of rituximab for patients with PNP in combination with follicular
      NHL is not always successful regarding oral lesions as we report in this case. PE
      leading to prompt depletion of autoreactive antibodies combined with
      immunosuppressants or synchronisation of PE with IVIg seems the best treatment
      modality for this refractory group, but the therapeutic value and appropriate
      timing of rituximab obviously deserve further evaluation in patients with low
      grade NHL and PNP.

PMID- 15512826
TI  - Autoimmune hemolytic anemia with myelodysplastic features followed by bilateral
      adrenal non-hodgkin lymphoma: a case report and review of the literature.
AB  - Primary adrenal lymphoma is a rare entity characterized mainly by bilateral
      involvement, presenting predominantly diffuse large B-cell histology, adrenal
      insufficiency and poor prognosis. Approximately 85 cases have been described in
      the literature. We report here a case of a 77-year-old man who presented with
      autoimmune hemolytic anemia (AIHA), which preceded the diagnosis of lymphoma by
      more than 2 years. An ultrasound guided biopsy revealed diffuse, large B-cell,
      lymphoma; subsequent staging revealed no other disease site, and the patient was
      considered to have primary adrenal lymphoma. The patient had adrenal
      insufficiency at diagnosis. He received hormonal replacement and chemotherapy,
      but he succumbed to his disease because of sepsis and multi-organ failure a few
      days post diagnosis. To our knowledge, this is the first case in the literature
      in which AIHA preceded bilateral adrenal lymphoma. We also provide a summary of
      the current data for the clinical features, diagnosis and treatment of primary
      adrenal lymphoma.

PMID- 15512827
TI  - Huge biatrial primary cardiac B-cell lymphoma resulting in bilateral
      atrioventricular valve obstruction.
AB  - We report the case of a 48-year-old man with a clinical syndrome caused by both
      pulmonary and systemic venous congestion. Echocardiography indicated a huge tumor
      occupying both dilated atria almost completely, seeming to invade from the atrial
      septum. A test for HIV was negative. Our primary diagnosis was a biatrial myxoma.
      Urgent surgery was performed disclosing large cell B-cell primary cardiac
      lymphoma. The patient died 8 days later. Primary cardiac lymphoma is extremely
      rare in immunocompetent patients. Its rarity and heterogenous clinical
      presentation make diagnosis difficult. As tissue characterization is still beyond
      the capabilities of currently available echocardiography, a combination of
      examinations are indicated, when the clinical condition is relatively stable, in
      order to reach the exact diagnosis.

PMID- 15512828
TI  - Viral load of human herpesvirus 8 (HHV-8) in the circulatory blood cells
      correlates with clinical progression in a patient with HHV-8-associated solid
      lymphoma with aids-associated Kaposi's sarcoma.
AB  - We encountered a case of a rapidly progressive HHV-8-associated solid lymphoma
      with AIDS-associated Kaposi's sarcoma (KS). HHV-8 DNA load in whole blood cells
      was analyzed quantitatively by real-time PCR using amplification of the HHV-8
      encoded ORF26 gene. Ours is the first observation that the rapid increase in the
      HHV-8 viral load (from 1.9x10(4) copies/microg to 1.6x10(6) copies/microg in 40
      days) in conjunction with low CD4+ cell counts was accompanied by an accelerated
      clinical disease progression. The results indicate that the quantity of
      circulating HHV-8 is measurable with real-time PCR and can provide clinically
      useful information.

PMID- 15512829
TI  - Severe hepatitis and complete molecular response caused by imatinib mesylate:
      possible association of its serum concentration with clinical outcomes.
AB  - A 40-year-old female with chronic myelogeneous leukemia (CML) in the chronic
      phase was treated with imatinib mesylate (STI571) because of interferon
      resistance. She achieved complete cytogenetic response but not complete molecular
      response 3 months after STI571 administration. Six months later, she developed
      severe liver damage without evidence of actively infectious hepatitis A, B, C, G,
      E, TT virus, Epstein-Barr virus or cytomegalovirus. A significant serum level of
      STI571 (107 ng/ml) was detected, although she had not taken the drug for 6 days.
      Liver biopsy demonstrated massive hepatic necrosis, consistent with drug-induced
      hepatitis. She achieved complete molecular response, although she did not take
      STI571 for 47 days after the development of hepatitis. These results suggest that
      both hepatitis and molecular response were associated with the serum STI571
      concentration.

PMID- 15512830
TI  - Combination treatment of rituximab and imatinib mesylate for simultaneous relapse
      of MALT lymphoma and a gastrointestinal stromal tumor.
AB  - A clinical case of patient with a simultaneous gastrointestinal stromal tumors
      (GIST) and MALT lymphoma in relapse is presented. Simultaneous treatment with
      imatinib mesylate and rituximab was given, yielded response for both tumors and
      was well tolerated.

PMID- 15512831
TI  - Gamma/delta T-cell lymphoma as a recurrent complication after transplantation.
AB  - We present a case of gamma-delta (gammadelta) T-cell lymphoma as a recurrent
      event in a pediatric liver transplant recipient. Liver transplantation was
      performed during infancy in an 18-month-old black girl because of cryptogenic
      cirrhosis. The patient received immunosuppression with cyclosporine and
      prednisone. Five years after transplantation, the patient was found to have a
      gammadelta T-cell lymphoma located in retroperitoneal nodes. She received
      chemotherapy and did well, remaining disease-free for 6 years. She remained only
      on prednisone for prevention of graft rejection, but was noted to have a non
      tender skin nodule that upon biopsy proved to be again a gammadelta T-cell
      lymphoma. However, comparison of tissue from both tumors revealed that the second
      occurrence of this malignancy was a de novo event, differing from the first by
      immunophenotypic and immunohistochemical characteristics, and TCR rearrangement.
      The patient continues to do well, without evidence of disease recurrence, after
      being treated again with chemotherapy. A summary of the literature is presented
      and comparison of our case is made.

PMID- 15512832
TI  - Teaching cases from the Royal Marsden and St Mary's Hospitals case 28: a patient
      with acute leukemia with rare leukemic cells of unusual morphology.

PMID- 15512833
TI  - Reduced dose imatinib mesylate therapy for chronic myeloid leukemia.

PMID- 15512835
TI  - Seasonal variability in behavioral despair in female rats.
AB  - Separate groups of female Wistar rats were tested every three months over a year
      to assess the extent of seasonal variability in the behavioral despair model of
      depression consisting of 2 swim tests separated by 24 h. There was a significant
      seasonal variability in the duration of immobility in the swim tests; duration of
      immobility was shorter in August and November than in February and May. These
      findings suggest reduced immobility and susceptibility to behavioral despair in
      summer and fall compared to winter and spring.

PMID- 15512836
TI  - Behavioral and neurochemical effects of the intrahippocampal co-injection of beta
      amyloid protein 1-40 and ibotenic acid in rats.
AB  - The authors investigated the effects of bilateral intrahippocampal co-injection
      of Abeta1-40 (4 microg for each side) with ibotenic acid (Ibo, 2 microg for each
      side) on rats' performance in the open field behavior, Y-maze, and passive
      avoidance task, and also examined some neurochemical changes in hippocampus two
      weeks after the co-injection. The results showed that the co-injection of Abeta1
      40 with Ibo induced a decrease in exploratory activity and a significant decline
      in learning-memory ability of the tested rats (p < .01). The neurochemistry
      changes induced by the co-injection included a significant decreased in membrane
      fluidity of hippocampal mitochondria (p < .01), a significant decrease in the
      activity of SOD (p < .01), and a remarkable increase in the content of MDA (p <
      .01). These results suggest that the co-injection of Abeta1-40 with Ibo may
      induce an increase of hippocampal damage by peroxidation, and a serious learning
      and memory impairment of the rats. The results also suggest that the co-injection
      of Abeta1-40 with Ibo may provide a useful animal model for Alzheimer's disease
      (AD) research.

PMID- 15512837
TI  - Handedness and bilateral femoral bone densities in men and women.
AB  - To examine the relation of hand preference to bilateral femoral bone mineral
      density (BMD), the right and left total and regional (neck, trochanter,
      intertrochanteric, and Ward's triangle) proximal femur BMDs (g/cm2) were measured
      using dual-energy X-ray absorbtiometry (DEXA) in 32 right- and 26 left-handed
      university students. The mean total BMD of the total right-handers and the mean
      trochanteric BMD of the right- handed males were greater in the left femur than
      the right femur. Contrarily, the total left-handers had higher mean
      intertrochanteric BMD in the right side than in the left side. There were
      negative correlations between R-L BMD differences and Geschwind scores of total,
      male, and female subjects. The results suggest that femur-BMD may be related to
      hand preference.

PMID- 15512838
TI  - No effect of skin anesthesia on pain intensity ratings associated with
      elicitation of the H-reflex in the soleus muscle.
AB  - This experiment evaluated the effect of a topical anesthetic on the intensity of
      pain experienced in response to elicitation of the H-reflex in the soleus muscle.
      Ten college-aged males provided ratings of pain intensity in response to
      elicitation of the H-reflex before and after topical application of skin
      anesthetic (5g EMLA) or placebo cream at the site of electrical stimulation in
      the popliteal fossa. The results indicated that (1) pain was experienced in
      association with the elicitation of both the H-wave and M-wave components of the
      H-reflex, and the skin anesthetic did not impact the pain intensity ratings; and
      (2) the skin anesthetic did not impact the amplitude of the H-wave, M-wave, and
      H/M Ratio recorded in the soleus muscle. The authors conclude that elicitation of
      the H-reflex in the soleus muscle results in low intensity pain, and the pain
      appears to be caused by activation of subcutaneous nociceptive afferent fibers of
      the tibial nerve.

PMID- 15512839
TI  - A mild acute compression induces neurapraxia in rat sciatic nerve.
AB  - The pressure that induces neurapraxia in rat remains unrevealed. To determine the
      appropriate force to induce neurapraxia, two types of clips were applied to the
      sciatic nerve and were evaluated with functional, electrophysiological, and
      histological examinations. With a compression of 60 g/mm2, walking track analysis
      showed complete sciatic nerve paralysis one day postoperatively, but became
      normal in 14 days. Electrophysiologically, complete conduction block occurred one
      day post operatively, whereas the motor conduction velocity (MCV) below the
      compression site remained normal. Histologically, only limited signs of Wallerian
      degeneration were seen. The model in this study exhibited the features of
      neurapraxia.

PMID- 15512840
TI  - Unilateral compression neuropathy of the hypoglossal nerve due to head suspension
      orthosis in mitochondriopathy.
AB  - An 85-year-old woman with multisystem mitochondriopathy experienced tension
      headache, cervical pain, torque head-posture, and vertigo since 1980 for which
      she was continuously wearing a head-suspension-orthosis- since 1990. Since 1996
      she developed severe left-sided weakness and wasting of the tongue. Needle-EMG of
      the left genioglossus muscle revealed abnormal spontaneous activity and reduced
      interference-pattern. No morphological alterations in the anatomical course of
      the hypoglossal nerve were found. Severe, unilateral weakness and wasting of the
      tongue was interpreted due to chronic compression of the hypoglossal nerve by
      long-standing use of a head-suspension-orthosis for cervical pain from cervical
      muscle weakness and resulting spinal degeneration.

PMID- 15512841
TI  - Hypersexuality and dysexecutive syndrome after a thalamic infarct.
AB  - Hypersexuality can result from insults to several neuroanatomical structures that
      regulate sexual behavior. A case is presented of an adult male with a thalamic
      infarct resulting in a paramedian thalamic syndrome, consisting of
      hypersomnolence, confabulatory anterograde amnesia (including reduplicative
      paramnesia), vertical gaze deficits, and hypophonic speech. A dysexecutive
      syndrome also manifested, consisting of social disinhibition, apathy,
      witzelsucht, motor inhibition deficits, and environmental dependence.
      Hypersexuality uncharacteristic of his premorbid behavior was evident in
      instances of exhibitionism, public masturbation, and verbal sexual obscenities.
      In contrast to the few previous reports of hypersexuality following thalamic
      infarct, this case neither involved mania nor hemichorea. The relevance of the
      mediodorsal thalamic nucleus in limbic and prefrontal circuits is discussed.

PMID- 15512842
TI  - Effects of estradiol on cognition evaluated with p300 in in vitro fertilization
      patients.
AB  - The authors planned to show the effect of high-level estrogen on cognitive
      functions, using P300 in the in-vitro fertilization (IVF) population. Eighteen
      IVF patients (mean age 31.39 +/- 5.01) without any detectable cognitive disorder
      were enrolled in this study. The authors measured N100, P200, N200, P300
      latencies and amplitudes at Cz and Fz recordings during the lowest and highest
      blood estradiol levels. P300 amplitudes were significantly reduced during the
      highest level of estradiol compared to the lowest level both at Fz and Cz
      recordings. The other subcomponents of P300 were not significantly influenced by
      blood estradiol levels. The results revealed a decline in the ability of task
      relevance and state of arousal when the estradiol level was the highest in the
      IVF patients.

PMID- 15512843
TI  - The effect of stimulated microglia conditioned media on BDNF gene expression of
      striatal astrocytes: quantification by real-time PCR.
AB  - It is well accepted that there is mutual relation between glia-glia and glia
      neuron in the central nervous system. In the present study, the authors aimed to
      evaluate the effect of microglia conditioned medium (MCM) on brain derived
      neurotrophic factor (BDNF) gene expression of astrocytes by quantitative real
      time polymerase chain reaction (PCR). Real-time PCR is one of the most recent
      techniques for determination of gene expression. It is the first choice when
      sensitivity, specifity and cost effectiveness are concerned. The authors present,
      for the first time, the settings of real-time PCR for quantification of BDNF gene
      expression of rat strital astrocytes. Astrocytes that cultured- from the striatum
      were incubated with conditioned medium of either Zymosan A stiumulated or
      unstimulated microglia which were cultured from striatum and cortex of the rat
      pups. Our results have shown that incubation with stimulated striatal MCM induced
      BDNF gene expression of striatal astrocytes (1.33 fold) when compared to
      astrocytes treated with regular medium or unstimulated striatal MCM. We have also
      seen the similar effect with cortical MCM implying that effect of MCM does not
      change with regionally different microglia.

PMID- 15512844
TI  - BacMam recombinant baculoviruses in G protein-coupled receptor drug discovery.
AB  - With completion of the sequencing of the human and mouse genomes, the primary
      sequences of close to 400 non-olfactory G protein-coupled receptors (GPCRs) have
      been determined. There are intensive efforts within the pharmaceutical industry
      to discover and develop new therapeutic agents acting via GPCRs. In addition,
      there is a concerted effort to identify potential new drug targets from the
      remaining 150+orphan GPCRs through the identification of their ligands. Access to
      functionally expressed recombinant receptors underpins both of these key drug
      discovery activities. Typically, GPCR drug discovery screening activities are
      carried out using mammalian cell lines stably expressing the target of interest.
      The influx of new receptor sequences originating from genomic sequencing efforts
      has caused a shift toward wider applications of transient rather than stable
      expression systems, especially in support of assays for orphan receptor ligand
      screening. Recombinant baculoviruses in which the polyhedrin promoter has been
      replaced with a mammalian promoter, termed BacMam viruses, were originally
      designed as potential new gene therapy delivery vehicles. This same technology
      offers numerous advantages as a transient expression system in the assay of
      membrane-expressed drug targets, including GPCRs. Data presented show that BacMam
      can be used rapidly to generate robust and pharmacologically authentic GPCR
      assays in several formats, with the potential to transform drug discovery
      screening processes for this gene family.

PMID- 15512845
TI  - Bulk is a determinant of oxymetazoline affinity for the alpha1A-adrenergic
      receptor.
AB  - The alpha1A-adrenergic receptor (AR) has a higher affinity for several agonists
      and antagonists compared to alpha1B or alpha1D ARs. Mutagenesis studies were used
      to determine residues potentially responsible for this subtype selectivity.
      Oxymetazoline has a 50-fold lower affinity for alpha1D ARs compared to alpha1A
      ARs and also displayed a significant loss of affinity for an alpha1A Leu-290 to
      Phe mutant. It was concluded that steric interactions between the alpha1D ARs Phe
      360 and the bulkytert-butyl group of oxymetazoline partially accounts for this
      lower affinity. Thus, the alpha1A AR binding pocket may more easily accommodate
      bulk at the paraposition of the phenyl ring than the alpha1D AR.

PMID- 15512846
TI  - Heterologous expression of G protein-coupled receptors in U-2 OS osteosarcoma
      cells.
AB  - Recombinant baculoviruses, in which the insect cell-specific polyhedrin promoter
      has been replaced with a mammalian cell-active expression cassette (BacMam
      viruses), are efficient gene delivery vehicles for many mammalian cell types.
      BacMam viruses have been generated for expression of G protein-coupled receptors
      (GPCRs) and used to establish Ca2+mobilization assays in HEK-293 human embryonic
      kidney cells and U-2 OS human osteosarcoma cells. U-2 OS cells are highly
      susceptible to BacMam-based gene delivery and lack many of the endogenous
      receptors present on HEK-293 and other mammalian cell lines typically used for
      heterologous expression of GPCRs. U-2 OS cells were found to have a null
      background for muscarine, ADP, ATP, UTP, UDP, and lysophosphatidic acid (LPA).
      Consequently, U-2 OS cells transduced with BacMam constructs encoding the
      muscarinic acetylcholine receptors (M1, M2, M3, M4, and M5subtypes), the P2Y
      receptors (P2Y1, P2Y2), or the LPA receptors (EDG-2, EDG-7) were used for the
      establishment of whole-cell Ca2+mobilization assays, assays that cannot readily
      be established in HEK-293 cells. U-2 OS cells were susceptible to simultaneous
      expression of multiple genes delivered by BacMam vectors. In U-2 OS cells the
      functional expression of the Gi-coupled M2and M4receptors was dependent on co
      expression of the receptor and a G protein chimera, both of which were delivered
      to the cells via BacMam viruses. The use of U-2 OS cells and BacMam-based gene
      delivery has facilitated development of whole-cell-based GPCR functional assays,
      especially for P2Y, muscarininc acetylcholine, and LPA receptors.

PMID- 15512847
TI  - Polyclonal antibody effects on the human cardiac 5-HT4(e) receptors depend upon
      the expression system.
AB  - The initial objective of this work was to examine the effects of an antibody
      (Anti-G21V) directed against the second extracellular loop of human heart 5-HT4
      receptors expressed in Chinese hamster ovary (CHO) cells. The antibody anti-G21V
      had no effect upon either basal cAMP-or 5-HT-evoked increases in cAMP in CHO
      cells, whereas it had shown an agonist-like effect in COS-7 cells. Analysis of
      agonist fractions of h5-HT4(e) receptors in CHO and COS-7 cells revealed that
      equilibrium constant could underlie the different responses of the receptor
      toward the anti-G21V antibody. Therefore, different expression systems could give
      rise to functional differences in 5-HT4 receptor behavior.

PMID- 15512848
TI  - Inactivation-deficient human skeletal muscle Na+ channels (hNav1.4-L443C/A444W)
      in stably transfected HEK-293 cells.
AB  - After transient transfection of an hNav1.4-L443C/A444W mutant clone, HEK-293
      cells exhibited large inactivation-deficient Na+currents. We subsequently
      established a stable cell line expressing robust inactivation-deficient
      Na+currents. Persistent late Na+currents were far more sensitive to block by
      class 1 anti-arrhythmic flecainide, mexiletine, propafenone, and amiodarone at 10
      microM than peak Na+currents. Such results support a hypothesis that persistent
      late Na+currents are in vivo targets for class 1 anti-arrhythmic drugs at their
      therapeutic plasma concentrations. Stably transfected HEK-293 cells expressing
      robust inactivation-deficient Na+currents will likely be suitable for screening
      novel drugs that target persistent late Na+currents selectively.

PMID- 15512849
TI  - Neuropeptide hormones and stress.

PMID- 15512850
TI  - Vasopressinergic regulation of the hypothalamic pituitary adrenal axis and stress
      adaptation.
AB  - Vasopressin (VP) stimulates pituitary ACTH secretion through interaction with
      receptors of the V1b subtype (V1bR, V3R), located in the plasma membrane of the
      pituitary corticotroph, mainly by potentiating the stimulatory effects of
      corticotropin releasing hormone (CRH). Chronic stress paradigms associated with
      corticotroph hyperresponsiveness lead to preferential expression of hypothalamic
      VP over CRH and upregulation of pituitary V1bR, suggesting an important role for
      VP during adaptation of the hypothalamic-pituitary-adrenal (HPA) axis to stress.
      Vasopressinergic regulation of ACTH secretion depends on the number of V1bRs as
      well as coupling of the receptor to phospholipase C (PLC) in the pituitary.
      Regulation of V1bR gene transcription may involve a number of regulatory elements
      in the promoter region, of which a GAGA box was shown to be essential. Although
      V1bR gene transcription is necessary to maintain V1bR mRNA levels, the lack of
      correlation between VP binding and V1bR mRNA suggests that regulation of mRNA
      translation is a major regulatory step of the number of V1bRs. V1bR translation
      appears to be under tonic inhibition by upstream minicistrons and positive
      regulation through protein kinase C (PKC) activation of an internal ribosome
      entry site (IRES) in the 5' untranslated region (5'UTR) of the mRNA. The data
      provide mechanisms by which regulation of hypothalamic VP and pituitary V1bR
      content contribute to controlling HPA axis activity during chronic stress.

PMID- 15512851
TI  - Vasopressin response to osmotic and hemodynamic stress: neurotransmitter
      involvement.
AB  - Osmotic and hemodynamic stress are the two primary regulators of vasopressin (VP)
      release from the posterior pituitary. The pathways providing information about
      plasma osmolality and blood pressure or blood volume are distinct and utilize
      different chemical neurotransmitters. Osmotic regulation of VP release is
      dependent upon afferents from the lamina terminalis region. Glutamate is an
      important transmitter in this system and angiotensinergic afferents from this
      region to the VP neurons modulate responses to osmotic challenges. Hemodynamic
      information is transmitted to the VP neurons via multisynaptic pathways from the
      brainstem with the A1 catecholamine neurons of the ventrolateral medulla
      providing the final link for information about decreases in blood pressure and
      volume. Several neurotransmitters and neuropeptides are expressed in the A1
      neurons including norepinephrine (NE), ATP, neuropeptide Y, and substance P. The
      impact of co-release of these agents on VP release is reviewed and the potential
      physiological significance is discussed.

PMID- 15512852
TI  - The activity of the hypothalamo-neurohypophysial system in response to acute
      stressor exposure: neuroendocrine and electrophysiological observations.
AB  - The present mini review focuses on stress-induced alterations of the electrical
      and secretory activity of vasopressin (AVP) and oxytocin (OXT) neurones
      originating within the supraoptic nucleus (SON) and constituting the hypothalamo
      neurohypophysial system (HNS) in the male rat. Previously, it was thought that
      SON neurones are predominantly activated by osmotic and reproductive stimuli.
      However, recent findings also suggest a selective activation of AVP and/or OXT
      neurones in response to specific stressors. Inhibitory amino acids seem to
      participate at the level of the SON in the control of HNS activity during stress.
      Taurine, probably of glial origin, selectively inhibits the secretory activity of
      AVP neurones. In contrast, GABA, probably of neuronal origin, interferes with the
      release of OXT both from axon terminals into blood and from somata/dendrites into
      the extracellular fluid of the SON. Depending upon whether a defined stressor
      triggers taurine and/or GABA release within the SON the secretion of AVP and/or
      OXT from HNS neurones will be inhibited. These observations shed new light on the
      neurone-neurone and glial-neurone interactions that ensure an appropriate
      neuroendocrine stress response.

PMID- 15512853
TI  - Cellular mechanisms underlying neuronal excitability during morphine withdrawal
      in physical dependence: lessons from the magnocellular oxytocin system.
AB  - Opiates are used clinically as analgesics, but their euphoric actions can lead to
      continued use and to dependence and addiction. While there are many factors
      involved in drug abuse, avoidance of stressful withdrawal symptoms is a key
      feature of addiction and its treatment. Fundamental to this is the need to
      understand the cellular processes that induce dependence and lead to the
      withdrawal syndrome. Many neurones in the brain express opioid receptors but only
      a few types of neurone develop dependence during chronic morphine exposure. The
      physiology of opiate-dependent cells is altered such that they require the
      continued presence of the drug to function normally and this is revealed, in
      cells that are inhibited by initial acute exposure to opiate, by a rebound
      hyperexcitation upon opiate withdrawal. Hypothalamic oxytocin neurones robustly
      develop morphine dependence and provide an exceptional opportunity to probe the
      cellular mechanisms underlying morphine dependence and withdrawal excitation.
      Although expression of morphine withdrawal excitation by oxytocin cells requires
      afferent inputs, the underlying mechanisms appear to reside within the oxytocin
      neurones themselves and probably involve changes in the intrinsic membrane
      properties of these neurones.

PMID- 15512854
TI  - Fos expression in CRF-containing neurons in the rat paraventricular nucleus after
      central administration of neuromedin U.
AB  - We examined the effects of centrally administered neuromedin U (NMU) on
      corticotrophin-releasing factor (CRF)-containing neurons in the hypothalamic
      paraventricular nucleus (PVN) of rats, using double immunohistochemistry for CRF
      and Fos. Almost all CRF-containing neurons in the parvocellular divisions of the
      PVN expressed Fos-like immunoreactivity 90 min after intracerebroventricular
      administration of NMU (3 nmol/rat). This results suggest the possibility that
      central NMU may be involved in stress-induced activation of CRF-containing
      neurons in the PVN.

PMID- 15512855
TI  - The influence of 17beta-oestradiol on corticotrophin-releasing hormone induced
      suppression of luteinising hormone pulses and the role of CRH in hypoglycaemic
      stress-induced suppression of pulsatile LH secretion in the female rat.
AB  - Corticotrophin-releasing hormone (CRH) released during stress has been implicated
      in the disruption of the reproductive neuroendocrine axis, and 17beta-oestradiol
      (E2) has been shown to enhance stress-induced suppression of pulsatile
      gonadotrophin-releasing hormone (GnRH) and luteinising hormone (LH) release. The
      aims of the present study were to examine the role of CRH in hypoglycaemic stress
      induced suppression of LH pulses, and to investigate the influence of E2 on the
      inhibitory effect of CRH on pulsatile LH secretion in the female rat. Suppression
      of LH pulses by insulin-induced hypoglycaemic (IIH) stress was completely
      prevented by intracerebroventricular (icv) administration of a CRH antagonist.
      Central administration of CRH (5 microg) resulted in an interruption of LH pulses
      in E2 treated animals, but had little or no effect in the absence of this gonadal
      steroid. These results provide evidence of a pivotal role for CRH in mediating
      the suppressive effect of IIH stress on pulsatile LH secretion in the female rat,
      and highlight a sensitising role for E2 in CRH-induced suppression of LH pulses.

PMID- 15512856
TI  - Effects of soy lecithin phosphatidic acid and phosphatidylserine complex (PAS) on
      the endocrine and psychological responses to mental stress.
AB  - Phosphatidylserine, derived from cow brains, has been shown previously to dampen
      the ACTH and cortisol response to physical stress. Further research investigated
      the influence of soy lecithin phosphatidylserine supplementation on mood and
      heart rate when faced with an acute stressor. In this study, we investigated the
      effects of soy lecithin phosphatidic acid and phosphatidylserine complex (PAS)
      supplementation on pituitary adrenal reactivity (ACTH, cortisol) and on the
      psychological response (Spielberger State Anxiety Inventory stress subscale) to a
      mental and emotional stressor. Four groups of 20 subjects were treated for three
      weeks with daily dosages of either 400 mg PAS, 600 mg PAS, 800 mg PAS, or placebo
      before exposure to the Trier Social Stress Test (TSST). Treatment with 400 mg PAS
      resulted in a pronounced blunting of both serum ACTH and cortisol, and salivary
      cortisol responses to the TSST, but did not affect heart rate. The effect was not
      seen with larger doses of PAS. With regard to the psychological response, 400 mg
      PAS seemed to exert a specific positive effect on emotional responses to the
      TSST. While the placebo group showed the expected increase in distress after the
      test, the group treated with 400 mg PAS showed decreased distress. These data
      provide initial evidence for a selective stress dampening effect of PAS on the
      pituitary-adrenal axis, suggesting the potential of PAS in the treatment of
      stress related disorders.

PMID- 15512857
TI  - 11Beta-hydroxysteroid dehydrogenase type 1 activity in medial vestibular nucleus
      and cerebellum after unilateral vestibular deafferentation in the rat.
AB  - In the early stages of vestibular compensation (VC) (the behavioural recovery
      that follows unilateral vestibular deafferentation), neurons in the medial
      vestibular nucleus (MVN) on the lesioned side develop a sustained up-regulation
      of their intrinsic excitability. This plasticity is dependent on the activation
      of glucocorticoid receptors, which presumably occurs during the acute stress
      response that accompanies the vestibular deafferentation symptoms. Recent studies
      have established that the access of glucocorticoids to their intracellular
      receptors in brain is potently modulated by 11beta-hydroxysteroid dehydrogenase
      type 1 (11beta-HSD1), which catalyses the generation of active glucocorticoids
      from their inert 11-keto forms. In this study, we investigated the presence of
      11beta-HSD1 bioactivity, and possible changes in activity in the early stage
      after vestibular deafferentation, in the cerebellar nodulus and uvula, the
      flocculus/paraflocculus (F/PF) complex and the MVN of the rat. 11beta-HSD1
      activity was found in each of these brain areas, with especially high levels of
      activity in the F/PF complex. No differences were found in the level of 11beta
      HSD1 activity in these brain areas between control rats, sham-operated rats and
      rats that underwent VC for 4 h after unilateral vestibular deafferentation. These
      findings demonstrate 11beta-HSD1 bioactivity in the MVN and vestibulocerebellum,
      but exclude the possibility that changes in 11beta-HSD1 activity occur in the
      early period after deafferentation, over the time when changes in MVN neuronal
      properties take place.

PMID- 15512858
TI  - Hemispheric asymmetry in stress processing in rat prefrontal cortex and the role
      of mesocortical dopamine.
AB  - The prefrontal cortex (PFC) is known to play an important role not only in the
      regulation of emotion, but in the integration of affective states with
      appropriate modulation of autonomic and neuroendocrine stress regulatory systems.
      The present review highlights findings in the rat which helps to elucidate the
      complex nature of prefrontal involvement in emotion and stress regulation. The
      medial PFC is particularly important in this regard and while dorsomedial regions
      appear to play a suppressive role in such regulation, the ventromedial
      (particularly infralimbic) region appears to activate behavioral, neuroendocrine
      and sympathetic autonomic systems in response to stressful situations. This may
      be especially true of spontaneous stress-related behavior or physiological
      responses to relatively acute stressors. The role of the medial PFC is somewhat
      more complex in conditions involving learned adjustments to stressful situations,
      such as the extinction of conditioned fear responses, but it is clear that the
      medial PFC is important in incorporating stressful experience for future adaptive
      behavior. It is also suggested that mesocortical dopamine plays an important
      adaptive role in this region by preventing excessive behavioral and physiological
      stress reactivity. The rat brain shows substantial hemispheric specialization in
      many respects, and while the right PFC is normally dominant in the activation of
      stress-related systems, the left may play a role in countering this activation
      through processes of interhemispheric inhibition. This proposed basic template
      for the lateralization of stress regulatory systems is suggested to be associated
      with efficient stress and emotional self-regulation, and also to be shaped by
      both early postnatal experience and gender differences.

PMID- 15512861
TI  - Randomized control trials in ALS: lessons learned.

PMID- 15512863
TI  - High throughput drug screening.

PMID- 15512862
TI  - Molecular targets for neuroprotection.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal paralytic neurodegenerative
      disorder. Experimental models of ALS such as the transgenic rodents expressing
      mutant superoxide dimutase-1 are playing a pivotal role in our understanding of
      ALS pathogenesis, and in our testing of new therapeutic interventions aimed at
      protecting against neurodegeneration. Apoptosis has emerged as a significant
      pathogenic factor in several neurodegenerative diseases, including ALS.
      Constructed of multiple interacting molecules, the apoptosis machinery offers a
      host of attractive targets for pharmacological and genetic interventions to be
      tested in experimental models of ALS. Information generated by these pre-clinical
      studies holds the promise to provide sound scientific basis for the development
      of effective neuroprotective therapies for ALS.

PMID- 15512864
TI  - Preclinical studies: how much can we rely on?

PMID- 15512865
TI  - ALS lessons learned from other neurological diseases. Parkinson's disease.

PMID- 15512866
TI  - ALS lessons learned from other neurological diseases. Stroke.

PMID- 15512867
TI  - ALS lessons learned from other neurological diseases. Neuro-oncology.

PMID- 15512868
TI  - Regulatory issues in ALS clinical trials.

PMID- 15512869
TI  - Randomized controlled trials.

PMID- 15512870
TI  - ALS issues in clinical trials. Statistical issues.

PMID- 15512871
TI  - Data Safety Monitoring Board (DSMB).

PMID- 15512872
TI  - ALS issues in clinical trials. Missing data.

PMID- 15512873
TI  - ALS trial design: expectation and reality.

PMID- 15512874
TI  - An efficient multi-stage, single-arm Phase II futility design for ALS.

PMID- 15512875
TI  - Improving efficiency of ALS clinical trials using lead-in designs.
AB  - We describe designs for clinical trials in ALS including two that are more
      efficient than the standard two-arm, parallel design. The more efficient designs
      incorporate a lead-in period followed by a randomized intervention (drug or
      placebo) period. Efficacy of the more efficient designs is based on measuring,
      within each patient, the difference in slope while on the new treatment compared
      to the lead-in period. We demonstrate, with sample size calculations, that the
      lead-in designs are considerably more efficient than the standard two-arm,
      parallel design. Sample sizes can be reduced by 44% for a 12-month study using
      ALSFRS rate of decline as a primary endpoint for a two-arm trial with 4 months
      lead-in compared to a parallel design. A sample size reduction of 70% can be
      realized with variable lead-in compared to a parallel design.

PMID- 15512876
TI  - Design using historical controls.

PMID- 15512877
TI  - Baseline disease characteristics.

PMID- 15512878
TI  - Disease-modifying drug therapies.

PMID- 15512879
TI  - Disease-modifying interventions.

PMID- 15512880
TI  - ALS endpoints. Survival.

PMID- 15512881
TI  - Maximum voluntary isometric contraction (MVIC).

PMID- 15512882
TI  - Assessment of strength measurements.

PMID- 15512883
TI  - ALSFRS-R.
AB  - The ALSFRS-R is an attractive primary outcome measure in clinical trials of ALS
      because it is validated, easy to administer, minimizes dropout, reduces cost, and
      correlates with survival. Unlike the other standard outcome measures currently
      employed, the ALSFRS-R is also a measure of global function.

PMID- 15512884
TI  - AALSS.

PMID- 15512885
TI  - Measuring pseudobulbar affect in ALS.

PMID- 15512886
TI  - Use of surrogate markers.

PMID- 15512887
TI  - ALS surrogate markers. MUNE.
AB  - Over the last decade, motor unit number estimation (MUNE) methods have been
      applied with increasing frequency to the study of amyotrophic lateral sclerosis.
      MUNE is the ideal tool for the assessment of diseases in which the primary defect
      is motor unit loss, as it enables quantitation and tracking of motor unit numbers
      while simultaneously gauging countervailing collateral reinervation. These
      properties make it particularly useful for assessing the effects of both
      neuroprotective therapies and therapies designed to enhance collateral
      reinervation, not only in animal models but also in the living patient. Previous
      studies have supplied important natural history information, confirming an
      average 50% loss of motor units for every six months of disease progression, and
      newer pathophysiological investigations are providing unique insight into motor
      unit behavior in the face of progressive anterior horn cell death. More recent
      efforts have incorporated MUNE into ongoing, multi-center clinical trials as a
      putative early biomarker, with encouraging results. As MUNE methods continue to
      be refined and disseminated, they are proving to be useful and unique tools for
      the study of motor neuron disease.

PMID- 15512888
TI  - The Neurophysiological Index in ALS.
AB  - The Neurophysiological Index (NI) consists of a mathematical derivation of three
      standardised neurophysiological measurements. Since these measurements are part
      of routine practice in any clinical neurophysiology laboratory, calculation of
      the NI is within the capability of any laboratory. The NI is derived from the
      CMAP, the DML and the F-wave frequency (CMAP amplitude/DML) x F frequency %),
      representing aspects of the effects of denervation and reinnervation, of
      degeneration of the terminal part of the motor axons, and of the excitability of
      anterior horn cells. We have shown that this simple index is reproducible in
      consecutive studies of normal subjects and of patients with ALS (intra-rater
      reliability), and is sensitive to change. In ALS, the NI differentiates rapidly
      and slowly progressive disease at least as sensitively as other measures in
      common use, including the ALS-FRS. We propose that the NI could be used as a
      sensitive measure of change during the course of ALS and its treatment. In
      combination with relevant measures of clinical benefit, such as ALS-FRS and a QoL
      measure, this could simplify trial design and allow more rapid determination of
      the efficacy of putative new therapies in clinical trials.

PMID- 15512889
TI  - ALS surrogate markers. MRS.
AB  - Magnetic resonance spectroscopy (MRS) allows the quantitative assessment of
      neuronal integrity in vivo based on the resonance intensity of N-acetylaspartate
      (NAA). A simple approach to quantitation that is commonly used is to quantify the
      resonance intensity of NAA with respect to creatine (Cr). In patients with ALS,
      NAA/Cr density is decreased in areas of the brain that contribute significantly
      to the corticospinal tract. Since MRS is non-invasive, it can be easily used to
      monitor the evolution of regional changes in NAA/Cr over time. The changes in
      NAA/Cr over a period of months are small, however, and challenge the precision of
      the method.

PMID- 15512890
TI  - ALS combination treatment. Drug cocktails.

PMID- 15512891
TI  - Sociology of collaborative research groups.

PMID- 15512892
TI  - Western ALS Study Group.

PMID- 15512893
TI  - North East ALS Study Group.

PMID- 15512894
TI  - Great Lakes ALS Study Group.

PMID- 15512895
TI  - The National Registry of Veterans with Amyotrophic Lateral Sclerosis: Department
      of Veterans Affairs Cooperative Studies Program (CSP) #500a.
AB  - In response to concern about the development of ALS among veterans of the U.S.
      armed forces, particularly Gulf War veterans, the Department of Veterans Affairs
      established a national registry of veterans with ALS. This Registry will identify
      living veterans with ALS, track the progression of their disease, and serve as a
      vehicle to facilitate study of epidemiological risk factors for ALS in a military
      context. The Registry will also function as a means of communication with the
      enrolled patients about basic and clinical ALS-specific research. Executive and
      scientific research committees guide the activity of the registry.

PMID- 15512896
TI  - European ALS Consortium.

PMID- 15512897
TI  - Future national study group in ALS.

PMID- 15512898
TI  - Patient orientated research and clinical trials.
AB  - The time is now ripe for the ALS community in the United States to set up a
      national ALS Study Group. NIH and other granting agencies should fund a program
      to set up and run the ALS Study Group for five years renewable. This program
      should result in a competitive request for applications. The benefits likely to
      derive from a national ALS Study Group would include cheaper and more cost
      effective clinical therapeutic trials, the development of better techniques for
      pilot trials, an increased number of potential new drugs brought from bench to
      bedside for ALS trials, increased research on biological and surrogate markers of
      disease, and increased physician-initiated research.

PMID- 15512899
TI  - Summing up: An action plan for ALS research.

PMID- 15512900
TI  - Breaking the news: a survey of ALS patients and their caregivers.
AB  - Breaking the news of the diagnosis of amyotrophic lateral sclerosis (ALS) is a
      formidable task. To evaluate the process from the perspective of patients and
      caregivers, we surveyed 94 patient-caregiver pairs, as well as 50 unpaired
      patients and 19 unpaired caregivers. We asked respondents to evaluate the
      physician who first broke the news of the diagnosis based on the time spent
      discussing the diagnosis, and six attributes of effective communication of bad
      news derived from the SPIKES protocol (setting, perception, invitation,
      knowledge, empathy, strategy). Fifty-six percent of patients rated the way the
      physician who broke the news as average (30.7), below average (8.6) or poor
      (16.4). Forty-eight percent of caregivers rated the physician as poor (14.4),
      below average (4.8) or average (28.8). Better performance on all attributes of
      effective communication as well as greater time spent discussing the diagnosis
      was correlated with higher patient/caregiver satisfaction. Our results suggest
      that there is room for improvement in breaking the news of the diagnosis of ALS.
      Greater adherence to certain attributes of effective communication of bad news
      may improve the way physicians perform this difficult task.

PMID- 15512901
TI  - Corticospinal tract degeneration and possible pathogenesis in ALS evaluated by MR
      diffusion tensor imaging.
AB  - BACKGROUND: MR diffusion tensor imaging (DTI) appears to be a powerful method to
      investigate the neuronal and axonal fibre distribution in the human brain.
      Changes in diffusion characteristics of water molecules in the white matter can
      be estimated as the apparent diffusion coefficient (ADC) and the fractional
      anisotropy index (FA). OBJECTIVES: To characterize DTI changes at three different
      levels in the corticospinal tract (CST) (corona radiata, internal capsule and
      pons) in order to elucidate if pathogenesis of ALS is due to an anterograde or
      retrograde axonal degeneration. METHODS: We studied eight ALS patients with
      clinical signs of upper motor neuron involvement. The patients were compared with
      11 healthy age-matched controls. RESULTS: ADC was significantly increased in the
      CST in ALS patients at the level of the internal capsule and also increased in
      the pons, but without statistical significance. ADC was unchanged at the level of
      the corona radiata. FA was significantly reduced at the lowest level (pons), only
      tended to be reduced in the internal capsule, but was also unchanged in the
      corona radiata. CONCLUSIONS: Segmentation of the CST into three regions supports
      the hypothesis of a 'dying back' mechanism in ALS and suggests that ADC is a more
      sensitive measure than FA to detect pathological changes in ALS.

PMID- 15512902
TI  - Reduced NAA in motor and non-motor brain regions in amyotrophic lateral
      sclerosis: a cross-sectional and longitudinal study.
AB  - OBJECTIVES: After replication of previous findings we aimed to: 1) determine if
      previously reported (1)H MRSI differences between ALS patients and control
      subjects are limited to the motor cortex; and 2) determine the longitudinal
      metabolic changes corresponding to varying levels of diagnostic certainty.
      METHODS: Twenty-one patients with possible/suspected ALS, 24 patients with
      probable/definite ALS and 17 control subjects underwent multislice (1)H MRSI co
      registered with tissue-segmented MRI to obtain concentrations of the brain
      metabolites N-acetylaspartate (NAA), creatine, and choline in the left and right
      motor cortex and in gray matter and white matter of non-motor regions in the
      brain. RESULTS: In the more affected hemisphere, reductions in the ratios,
      NAA/Cho and NAA/Cre+Cho were observed both within (12.6% and 9.5% respectively)
      and outside (9.2% and 7.3% respectively) the motor cortex in probable/definite
      ALS. However, these reductions were significantly greater within the motor cortex
      (P<0.05 for NAA/Cho and P<0.005 for NAA/Cre+Cho). Longitudinal changes in NAA
      were observed at three months within the motor cortex of both possible/suspected
      ALS patients (P<0.005) and at nine months outside the motor cortex of
      probable/definite patients (P<0.005). However, there was no clear pattern of
      progressive change over time. CONCLUSIONS: NAA ratios are reduced in the motor
      cortex and outside the motor cortex in ALS, suggesting widespread neuronal
      injury. Longitudinal changes of NAA are not reliable, suggesting that NAA may not
      be a useful surrogate marker for treatment trials.

PMID- 15512903
TI  - Oropharyngeal dysphagia in amyotrophic lateral sclerosis: neurological and
      dysphagia specific rating scales.
AB  - BACKGROUND: Oropharyngeal dysphagia is highly prevalent in amyotrophic lateral
      sclerosis (ALS). Patients with dysphagia and weight loss are frequently offered
      gastrostomy. Although the neurological basis of dysphagia in ALS is complex,
      there are currently no specifically validated scales for dysphagia in ALS, and
      the reliability of existing generic scales has not been assessed. METHODS: We
      undertook a prospective study of 25 patients who fulfilled the criteria for
      definite or probable ALS. We examined the reliability of the Dysphagia Outcome
      Severity Scale (DOSS) and the Aspiration-Penetration Rating Scale (APRS) and the
      correlation between these scales and the Norris ALS Scale and ALS Functional
      Rating Scale-R (ALS FRS-R). RESULTS: Using the Pearson Product-Moment
      Correlation, an expected high linear association between the two disease specific
      neurological scales was demonstrated. Both dysphagia scales were found to be
      reliable. Interrelationship evaluation showed a low association between Norris
      and ALS FRS-R scores and DOSS and APRS. However, examination found specific
      subsections to be significantly correlated, particularly the Norris bulbar
      sections (NBS) and the DOSS. CONCLUSIONS: Generic dysphagia scales are reliable
      indicators of dysphagia in ALS. The bulbar components of the ALS specific scales
      is sensitive to dysphagia. The bulbar section of the Norris scale can be utilised
      as an independent and reliable indicator of the severity of dysphagia in ALS. In
      the absence of availability of detailed swallowing assessment using
      videofluoroscopy, these scales, i.e., the Norris and to a lesser degree the ALS
      FRS-R bulbar sections, are adequate to diagnose and follow clinically significant
      dysphagia in ALS, and can be used as an indicator for dysphagia treatment
      initiation.

PMID- 15512904
TI  - Mirror movements and ipsilateral motor evoked potentials in ALS.
AB  - It can be difficult to detect upper motor neuron (UMN) involvement in early
      amyotrophic lateral sclerosis (ALS). The present study tested the usefulness of
      mirror movements (MMs), i.e., contralateral coactivation of hand muscles, as a
      UMN sign in ALS. Thirty-seven patients with possible, probable or definite ALS
      and 19 patients with suspected ALS without clinical signs of UMN involvement, 21
      disease controls and 15 healthy volunteers were included. MMs were studied
      clinically, electromyographically and by transcranial magnetic stimulation (TMS),
      looking for ipsilateral motor evoked potentials (IMEPs). MMs were observed
      clinically in 15 ALS patients (27%) and electromyographically in 28 (50%). IMEPs
      in the abductor pollicis brevis muscle following TMS were recorded in 34 (61%) of
      all ALS patients and in nine (47%) out of 19 patients with suspected ALS, but not
      in healthy controls. Central motor conduction times were prolonged in 15 ALS
      patients (27%). It is concluded that MMs, especially if studied by EMG and TMS
      (IMEPs) can essentially improve detection of UMN involvement, especially in early
      stages of ALS.

PMID- 15512905
TI  - Temporal gene expression patterns in G93A/SOD1 mouse.
AB  - Amyotrophic lateral sclerosis (ALS) is a generally fatal degenerative disorder of
      motor neurons that has no known cure. Many pathological processes have been
      implicated. However, the early, initiating events in the disease are poorly
      understood. We performed multivariate analyses of gene expression of 21 selected
      genes from categories including glutamate neurotoxicity, oxidative stress,
      neuroinflammation, aberrant metal ion regulation, apoptosis, and abnormal
      microglial function on G93A SOD1 mice. These animals develop symptoms of motor
      neuron dysfunction at about 12 weeks of age, and die at age 18 to 20 weeks. We
      analyzed animals at both presymptomatic and symptomatic stages. Differential
      regulation of several genes involved in neuroinflammation, including TNF-alpha,
      IL- RA, CD86, CD200R and Groalpha, was observed in presymptomatic mice, aged 6-9
      weeks, while expression of genes representative of other processes was not
      altered until the animals reached symptomatic stages. Analysis of expression of
      inflammatory genes and microglia related genes together also revealed a highly
      significant change in mutant mice relative to wildtype at 6-9 weeks. These
      changes were due to the presence of the mutant gene, and not simply to
      overexpression of a SOD1 gene. These findings are discussed in relation to
      possible roles of microglia function in the development of ALS.

PMID- 15512906
TI  - (-)-Deprenyl alleviates the degenerative changes induced in the neonatal rat
      spinal cord by CSF from amyotrophic lateral sclerosis patients.
AB  - Previous studies from our laboratory suggest the presence of toxic factor(s) in
      the cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis
      (ALS) which induces degenerative changes in the spinal cord neurons. The present
      work was carried out to investigate the role of (-)-deprenyl in attenuating these
      degenerative changes. CSF samples from ALS and non-ALS neurological patients were
      injected into the spinal subarachnoid space of 3-day-old rat pups, followed by a
      single dose (0.01 mg/kg body weight) of (-)-deprenyl, administered 24 h after CSF
      injection. After a further period of 24 h, the rats were sacrificed and the
      spinal cord sections were stained with antibodies against phosphorylated
      neurofilament (NF, SMI-31 antibody) and glial fibrillary acidic protein (GFAP).
      Activity of lactate dehydrogenase (LDH) was also measured. (-)-Deprenyl injection
      resulted in a significant (61%) decrease in the number of SMI-31 stained neuronal
      soma in the ventral horn of the spinal cord of ALS CSF exposed rats. This was
      accompanied by a reduction in the astrocytes immunoreactive for GFAP. There was
      also a significant (35%) decrease in the LDH activity following (-)-deprenyl
      treatment. These results suggest that (-)-deprenyl may confer neuroprotection
      against the toxic factor(s) present in ALS CSF.

PMID- 15512907
TI  - Selective vulnerability in amyotrophic lateral sclerosis: no evidence for a
      contribution of annexins, a family of calcium binding proteins.
AB  - Clinically, amyotrophic lateral sclerosis (ALS) usually presents as a pure motor
      system disorder, whereas oculomotor and sphincter muscle control of the anus and
      the bladder appear to be spared. Previously, a lacking expression of calcium
      binding proteins (CBPs) was demonstrated in vulnerable motor neurons in contrast
      to spared neuronal populations, e.g., the motor neurons of the cranial nerve III
      (NO) and the Onufrowicz nucleus (ON), suggesting a potential role of CBPs in the
      selective motoneuronal vulnerability in ALS. The annexins comprise a multigene
      family of CBPs, constituting a significant amount of total cellular protein and
      presumably involved in calcium-homeostasis and intracellular calcium-regulated
      pathways. We immunohistochemically investigated the expression patterns of
      annexins A1, A2, A4, A5, A6, and A7 in spinal cord and midbrain tissues from 24
      ALS patients and 5 age-matched controls to test the hypothesis that annexins also
      contribute to the selective vulnerability in ALS. There was no difference in the
      expression patterns of ALS cases and normal controls. Annexin A1 was expressed in
      ependymal cells and motor neurons. Annexin A2 could be detected in ependymal and
      endothelial cells and motor neurons. Annexins A4 and A5 were found in both
      ependymal and glial cells, whereas annexin A6 was strongly expressed in motor
      neurons. Annexin A7 was totally absent from central nervous system tissue. A
      contribution of annexins to the selective vulnerability in ALS could not be
      derived from our results.

PMID- 15512908
TI  - Motor neuron disease and optic neuropathy after acute exposure to a methanol
      containing solvent mixture.
AB  - A 34-years-old floor-layer developed optic neuropathy and motor neuron disease
      after being accidentally exposed to a solvent mixture containing methanol and
      other substances. Optic neuropathy is a complication of methanol poisoning, but
      the onset of a motor neuron disorder resembling amyotrophic lateral sclerosis
      after the exposure to these substances has not been previously described. The
      temporal onset of the clinical symptoms, biological plausibility, young age of
      the patient and absence of neurological disorders in the family history raises
      suspicion of a possible causative relationship.

PMID- 15512909
TI  - Stem cell transplants for heavily transfused patients with severe aplastic
      anemia: a promising new strategy.

PMID- 15512910
TI  - An APC for every occasion: induction and expansion of human Ag-specific CD4 and
      CD8 T cells using cellular and non-cellular APC.
AB  - APC are used extensively to induce and expand Ag-specific T cells as well as to
      test their specificity and function. In the treatment of malignant and infectious
      diseases, APC are used to stimulate and expand Ag-specific T cells for adoptive
      transfer, or used directly in vivo to present Ag. The choice of APC to use
      depends on the particular application and on practical considerations, which
      include ease of production, availability, reproducibility and (for clinical use)
      established safety. The diversity of APC in use partly reflects the fact that no
      single technique of Ag presentation is ideal. For the clinician and laboratory
      worker alike the field can seem illogical and confusing. In this review we
      outline the functional requirements of APC for the induction of T cells, classify
      the APC in common use and describe their laboratory and clinical applications.

PMID- 15512911
TI  - Radiotherapy-based conditioning is effective immunosuppression for patients
      undergoing transplantation with T-cell depleted stem cell grafts for severe
      aplasia.
AB  - BACKGROUND: We studied the outcome of individuals with aplastic anemia
      conditioned with a radiation-containing regimen followed by an infusion of stem
      cell grafts that had been depleted of lymphocytes with CAMPATH-1H (antiCD52;
      humanised). METHODS: The conditioning regime consisted of fractionated (f) TBI 8
      Gy followed by f total nodal irradiation (TNI) 6 Gy. In addition, patients
      received CY 60 mg/kg on 2 consecutive days. Cytokine-mobilized peripheral blood
      grafts from HLA-identical siblings were T-cell depleted with CAMPATH-1H 'in the
      bag'. CsA was commenced on day -1 and continued until day +90. RESULTS: Seventeen
      heavily transfused patients with aplastic anemia, median age 18 years (range 14
      56 years), were studied. The median time from diagnosis to transplantation was
      172 days (range 34-443 days). The median CD34(+) cell number infused was 3.47 x
      10(6)/kg (range 1.03-18.4 x 10(6)/kg). All patients engrafted. Recovery was fast
      and patients reached 0.5 x 10(9)/L polymorphs by median day 11 (range 9-17 days).
      Toxicity from the conditioning included grade 4 hematologic toxicity in all
      patients. Another major toxicity was gastrointestinal mucosal damage, which
      exceeded grade 2 in two instances. One patient developed thrombotic
      thrombocytopenic purpura, which responded to substitution of CsA with tacrolimus
      and plasmapheresis. Another patient, who had normal blood counts, died of
      infection on day 241. Chimerism studies at 6 months post-transplantation
      confirmed the donor origin of hematopoiesis in all seven patients tested. None of
      the patients developed acute or chronic GvHD. There was no delayed graft failure
      and 94% of patients had survived disease free at a median of 1303.5 days (range
      216-2615 days) from graft infusion. DISCUSSION: In this cohort of multiply
      transfused patients, the radiation-containing schedules described in this study
      led to universal engraftment with limited toxicity despite T-cell depletion. No
      patient developed GvHD or late graft failure. Lower doses of radiation-containing
      conditioning should be explored further.

PMID- 15512912
TI  - Comparison of total nucleated cell measurements of UC blood samples using two
      hematology analyzers.
AB  - BACKGROUND: The total nucleated cell (TNC) content of umbilical cord blood (UCB)
      units currently serves as the most important measure for determining suitability
      for transplantation. Hence it is important that TNC measurements are performed in
      an accurate manner. TNC content is evaluated routinely by hematology analyzers
      (HA) as WBC counts. The objective of the study was to compare TNC content
      utilizing two different HA, one utilizing an impedance channel and optical
      channel, and the other using only an optical channel. METHODS: The HA utilized in
      this study used two different modes of operation for lysis, regular mode (RM) and
      extended lysis mode (ELM). Cell-Dyn 3200 (CD3.2) utilizes optical technology for
      WBC measurements, involving WBC optical count (WOC) and nuclear optical count
      (NOC), whereas the Cell-Dyn 3700 (CD3.7) utilizes both the impedance (WIC) and
      optical technology (WOC) for WBC measurements. TNC content was determined with 17
      identical samples using CD3.2 in one laboratory and CD3.7 in the other
      laboratory. Cord blood samples processed to concentrate nucleated cells by either
      of the laboratories were sent by overnight courier and assays were performed on
      the same day by both laboratories. RESULTS: For CD3.7, the WOC values were
      consistently lower than the WIC using the regular mode, but showed no significant
      differences (P>0.05). The WIC and WOC values were comparable on using the ELM and
      RM. For CD3.2, WOC values using RM and NOC values using ELM showed no significant
      differences (P>0.05), even though the WOC measurement was lower than the NOC
      values for most samples. The best comparison of TNC measurement between the two
      HA could be achieved by comparing CD3.7-WIC with CD3.2-NOC values. The results
      were equivalent (P>0.05) and 12 of 17 samples had equal to or less than 10%
      difference (mean 9.5%). DISCUSSION: TNC measurements of UCB samples were
      essentially identical using the WIC channel of the Cell-Dyn 3700 and the NOC
      channel of the Cell-Dyn 3200.

PMID- 15512913
TI  - Role of beta(1)-integrins and their associated tetraspanin molecules in
      fibronectin-enhanced megakaryopoiesis.
AB  - BACKGROUND: We have shown previously that fibronectin (FN) together with
      megakaryocyte (Mk) growth and development factor (MGDF) enhanced generation of Mk
      progenitors determined by colony-forming unit (CFU)-Mk assay. MGDF can activate
      beta(1)-integrins on progenitor cells and increase binding to FN. We studied the
      role of beta(1)-integrin-tetraspanin complexes by which FN may enhance
      megakaryopoiesis. METHODS: Cord blood CD34(+) cells were cultured for up to 8
      days in serum-free medium containing IL-3, IL-6 and SCF with or without MGDF in
      the presence or absence of FN. Immunofluorescence flow cytometry was used to
      monitor changes in beta(1)-integrin-tetraspanin complexes. CFU-Mk assay was used
      to assess Mk commitment. RESULTS: The cocktail of cytokines irrespective of the
      presence of MGDF altered the percentage expression of beta(1)-integrins CD49d and
      CD49e on CD34(+) cells. CD49d expression fell initially (98% to 15%) and then
      rose to 75%, whereas CD49e progressively increased over the 8 days of culture,
      from 5.4% to 22%. However, with the addition of FN, similar changes in the
      expression of beta(1)-integrins were observed but the expression was maintained
      at a higher level. MGDF and FN increased expression of tetraspanin molecules,
      CD63 and CD151, as well as their co-expression with the beta(1)-integrins on both
      the CD34(+) and CD34(-) cells (e.g. and increase from 0% to 80% co-expression of
      CD49d and CD151 on CD34(+)). Blocking of beta(1)-integrins or the tetraspanin
      CD151 with the respective MAb reduced Mk progenitor generation in a stromal cell
      model. DISCUSSION: FN enhanced Mk progenitor generation through modulation of
      beta(1)-integrin-tetraspanin complexes, such as CD151/CD49d.

PMID- 15512914
TI  - Mesenchymal stem/progenitor cells developed in cultures from UC blood.
AB  - Background Whether umbilical cord blood (UCB) serves as a source of mesenchymal
      stem/progenitor cells (MSPC) is controversial. MSPC are the best candidates for
      cellular therapy of orthopedic skeletal tissues. In order to explore the
      possibility of UCB as a useful source of MSPC, we identified, expanded in
      culture, and characterized MSPC from UCB harvests on a large scale. Methods
      Mononuclear cells isolated from UCB harvests (n=411) were cultured in media
      supplemented with 10% FBS. MSPC-like cells cultured from each UCB harvest were
      expanded ex vivo by successive subcultivation. UCB harvests with a more than 1000
      fold expanding capacity (n=9) were examined for surface Ag phenotypes and in
      vitro differentiation potentials into osteogenic, chondrogenic and adipogenic
      lineages. Results Ninety-five out of a total of 411 UCB units (23.1%) generated
      MSPC-like cells during cultivation. Nine UCB units (2.2%) yielded MSPC with more
      than 1000-fold expansion capacity. These cells positively expressed MSPC-related
      Ag, but did not express myeloid, histocompatibility or endothelial Ag. These
      cells also possessed multiple capacities for osteogenic, chondrogenic and
      adipogenic differentiation. Discussion Although the incidence of UCB harvests
      producing MSPC in culture was low, some of them showed a more than 1000-fold
      expanding capacity, which is enough in cell numbers to be an allogeneic source
      for cellular therapy. Our results may encourage the use of UCB as an attractive
      target for allogeneic cellular therapeutic options in tissue engineering.

PMID- 15512915
TI  - Activated platelets rapidly up-regulate CD40L expression and can effectively
      mature and activate autologous ex vivo differentiated DC.
AB  - Background DC are a promising immunotherapeutic for treatment of
      infectious/malignant disease. For clinical trials, immature DC generated from
      precursor cells such as monocytes, using serum-free media containing GM-CSF and
      IL-4, can be matured with specific cytokines/factors. CD40 ligand (CD40L) plays
      an important role in DC activation/maturation but is not available for clinical
      applications. These studies evaluated the feasibility of using activated
      platelets with elevated CD40L surface expression to stimulate autologous DC
      maturation. Methods Pilot and clinical scale studies were executed using
      magnetic/centrifugal separation. Monocyte precursors were differentiated to
      immature DC with GM-CSF and IL-4 and the ability of activated autologous
      platelets to mature these cells was evaluated on the basis of phenotype and
      function. Results In small-scale studies, DC cultures stimulated with activated
      autologous platelets (CD40L-AP), tumor necrosis factor-alpha (TNF-alpha) or
      soluble CD40L (sCD40L) up-regulated expression of phenotype markers indicative of
      activation and maturation. CD86 expression was significantly enhanced (P<0.05) by
      stimulation with either CD40L-AP (75.5+/-14.5%) or sCD40L (80.5%+/-5.3%) compared
      with immature DC (55.2+/-14.8%), as were CD80 and CD83. Similarly, in large-scale
      studies using Isolex 300I to enrich for monocytes and platelets for DC
      generation/maturation on a clinical scale, stimulation with CD40L-AP increased
      CD86 and CD80 expression as well as the ability to stimulate allogeneic
      lymphocytes compared with control cultures. Discussion These results demonstrate
      that thrombin-activated platelets express CD40L and are effective at inducing
      matured DC with potent immunogenic activity. Furthermore, these studies
      demonstrate the feasibility of this approach for clinical immunotherapeutic
      interventions.

PMID- 15512917
TI  - Real-time process/quality control for HPC processing.
AB  - BACKGROUND: JACIE Standards (FACT Standards in the USA) have been implemented in
      Europe since 1999. An on-site accreditation inspection took place at our center
      in January 2004. The purpose of this work was to develop a real-time
      process/quality control system meeting the JACIE Standards for HPC release.
      METHODS: Data from 194 HPC processing procedures for autologous transplantation
      performed over a 5-year period were analyzed. The results of different processing
      methods applied at our facility were compared: (1) cryopreservation without
      washing cells (n=50), (2) washing cells (n=87), (3) cell-density separation
      (n=12) and (4) positive CD34 selection (n=45). RESULTS: Four critical control
      points were set for the validation of HPC processing: (a) number of lost CD34(+)
      cells during processing, (b) contamination, (c) viability of the cells after
      thawing and (d) ability to reconstitute hematopoiesis after transplantation. On
      the basis of statistical analysis, ranges of acceptable values were defined for
      each critical control point and for each processing method. Those acceptable
      values were used for cell release and real-time quality control. DISCUSSION: This
      study describes a model for the validation of HPC processing and for a real-time
      process/quality control system for HPC release. Optimization of processing
      techniques, standardization of methods and comparison between facilities will
      open the way towards external quality controls and quality improvement.

PMID- 15512916
TI  - Impaired PBPC collection in patients with myeloma after high-dose melphalan.
AB  - BACKGROUND: Tandem stem cell transplantation is an important treatment option for
      patients with myeloma and some additional tumors. In an attempt to reduce the
      contamination of the stem cell graft with tumor cells, patients with myeloma who
      entered complete remission after the first transplant underwent a second episode
      of mobilization to obtain progenitor cells for the second transplant. METHODS:
      Twenty-two patients with myeloma participated in the study. The first
      mobilization utilized CY, etoposide and filgrastim. The second mobilization used
      the same regimen, but seven patients received only filgrastim. The interval
      between the two collection periods was 6 months (median; range 4-9 months). The
      preparative regimen for the first transplant consisted of melphalan 200 mg/m(2).
      RESULTS: The number of total white cells collected during the two collection
      episodes was similar: 10.8+/-1.6 x 10(8)/kg white cells vs. 11.8+/-1.7 x 10(8)/kg
      white cells (P=0.63). The collected CD34(+) cell dose was much larger during the
      first collection: 45.2+/-8.4 x 10(6)/kg vs. 6.9+/-2.7 x 10(6)/kg (P<0.001).
      Similarly, the collected colony-forming unit (CFU)-GM dose was much larger during
      the first collection: 295.4+/-59.3 x 10(4)/kg vs. 67.3+/-21.6x10(4)/kg (P<0.001).
      While the CD34(+) cells collected during the two collection episodes correlated
      significantly (r=0.55, P<0.01); the first dose was a median of 14.9-fold larger.
      DISCUSSION: No laboratory parameter was able reliably to predict the results of
      the second collection. A second mobilization/collection episode as part of a
      tandem transplant approach carries a considerable risk of failing to obtain
      sufficient progenitor cells.

PMID- 15512918
TI  - Expansion of human CMV-specific cytotoxic T lymphocytes to a clinical scale: a
      simple culture system using tetrameric HLA-peptide complexes.
AB  - BACKGROUND: Recipients of allogeneic stem cell transplants (SCT) are at risk of
      human CMV infection during their immunocompromised period. The increasing number
      of reports of CMV isolates resistant to ganciclovir after transplantation has led
      us to attempt to develop alternative strategies for preventing or treating CMV
      infection. This study describes a system for generating sufficient numbers of CMV
      specific cytotoxic T lymphocytes (CTL) for adoptive immunotherapy after SCT.
      METHODS: CMV-specific CTL were isolated from a single blood draw of a CMV
      seropositive donor using PE-labeled HLA-A*0201/pp65(495-503) tetramers and anti
      PE magnetic beads. A mixture of a tetramer-positive population and CD4(+) T
      lymphocytes was expanded to sufficient numbers for clinical application with IL-2
      and immobilized anti-CD3 stimulation. RESULT: Starting from 50 mL of blood, we
      generated >10(7)/m(2) tetramer-positive CTL within 2 weeks. Flow cytometric
      analysis of expanded lymphocytes showed that purity of CMV peptide-specific CTL
      was >75%. Upon stimulation of HLA-A*0201-restricted CMV peptide, expanded CD8 T
      lymphocytes produced intracellular IFN-gamma. Purified CTL exhibited cytotoxic
      activity against CMV peptide-pulsed T2 cells and CMV-infected HLA-A*0201-positive
      fibroblasts, but not against HLA mismatched or uninfected target cells.
      Alloreactivity could be excluded in MLC. DISCUSSION: This simple, rapid culture
      system can be useful for adoptive immunotherapy after allogeneic SCT. We are now
      trying to adapt our laboratory scale study to a clinical scale study under good
      manufacturing practices (GMP) conditions.

PMID- 15512919
TI  - Intraoperative isolation and processing of BM-derived stem cells.
AB  - To improve tissue regeneration of ischemic myocardium, autologous bone marrow
      derived stem cells have been injected intramyocardially in five patients
      undergoing coronary artery bypass grafting and transmyocardial laser
      revascularization. An innovative method for the intraoperative isolation of
      CD133(+)-stem cells in less than 3 hours has been established. After induction of
      general anesthesia, approx. 60-240 ml of bone marrow were harvested from the
      posterior iliac crest and processed in the operating room under GMP conditions
      using the automated cell selection device Clini-MACS. Following standard CABG
      surgery, LASER channels were shot in predefined areas within the hibernating
      myocardium. Subsequently, autologous CD133(+)-stem cells (1.9-9.7 x 10(6) cells;
      purity up to 97%) were injected in a predefined pattern around the laser
      channels. Through the intraoperative isolation of CD133(+)-cells, this effective
      treatment of ischemic myocardium can be applied to patients scheduled both for
      elective and for emergency revascularisation procedures.

PMID- 15512921
TI  - Editorial statement: disclosure of funding sources and financial interests by
      authors.

PMID- 15512922
TI  - Predictive validity of global deficit scores in detecting neuropsychological
      impairment in HIV infection.
AB  - The current study explored the predictive validity of the Global Deficit Score
      (GDS) approach in summarizing neuropsychological (NP) test results, and
      specifically in detecting HIV-associated cognitive impairment. A comprehensive NP
      test battery was administered to 88 HIV+ subjects and 61 healthy HIV- controls
      comparable for age, education, and ethnicity. Demographically corrected test data
      were converted to a GDS, which simulates clinicians' ratings by quantifying the
      number and degree of impaired performances throughout the test battery while
      attaching relatively less significance to superior performances and/or those
      within normal limits. Our results indicated that the GDS approach effectively
      discriminated HIV+ and normal control groups, and accurately classified HIV+
      individuals with NP impairment based on the "gold standard" clinical rating
      approach. Consistent with previous studies using different subject samples and
      different NP test batteries, the GDS cutpoint of >or=0.50 yielded optimal balance
      between sensitivity and specificity in classifying NP impairment, thus supporting
      the generalizability of the method. Moreover, the ability of the GDS to predict
      NP impairment across several cutpoints was quite strong, with positive predictive
      power values ranging from 0.71 to 1.00. These findings support the validity of
      the GDS as a clinically useful way of summarizing results on NP testing.

PMID- 15512923
TI  - Enhancing power while controlling family-wise error: an illustration of the
      issues using electrocortical studies.
AB  - This study examined the relative family-wise error (FWE) rate and statistical
      power of multivariate permutation tests (MPTs), Bonferroni-adjusted alpha, and
      uncorrected-alpha tests of significance for bivariate associations. Although
      there are many previous applications of MPTs, this is the first to apply it to
      testing bivariate associations. Electrocortical studies were selected as an
      example class because the sample sizes that are typical of electrocortical
      studies published in 2001 and 2002 are small and their multiple significance
      tests are typically nonindependent. Because Bonferroni adjustments assume
      independent predictors, we expected that MPTs would be more powerful than the
      Bonferroni adjustment. Results support the following conclusions: (a) failure to
      control for multiple significance testing results in unacceptable FWE rates, (b)
      the FWE rate for the MPTs approximated the alpha set for the analyses, and (c)
      the statistical power advantage that MPTs provide over Bonferroni adjustments is
      important when using small sample sizes such as those that are typical of recent
      electrocortical studies.

PMID- 15512924
TI  - Dual-task performance in early stage dementia: differential effects for
      automatized and effortful processing.
AB  - Attentional functions of individuals with early stage Alzheimer's disease (AD)
      and normal older adults (NC) were studied using a concurrent-task paradigm.
      Fourteen patients (5 men, 9 women) and 14 age- and sex-matched normal adults
      engaged in speeded unimanual tapping and speaking tasks during single- and dual
      task trials. Speaking tasks were either relatively automatized (Speech
      Repetition) or relatively effortful (Speech Fluency). As single-task tapping
      rates were slower for the AD participants than for the NC participants, a
      proportional decrement score was used as an index of interference in the dual
      task conditions. Interference during concurrent-task performance was greater when
      the cognitive task was effortful for both the NC and the AD groups. Although AD
      patients suffered higher levels of interference than NC participants while
      performing the effortful speech task, the two groups showed equivalent small
      changes in tapping speed while combining the automatized speaking and tapping
      tasks. Results suggest that a general-purpose attentional processing resource
      declines in the early stages of AD but dual-task performance is well-maintained
      when the component tasks are relatively automatized.

PMID- 15512925
TI  - Preservation of reasoning in primary progressive aphasia: further differentiation
      from Alzheimer's disease and the behavioral presentation of frontotemporal
      dementia.
AB  - Primary Progressive Aphasia (PPA) is a clinical dementia syndrome characterized
      by the gradual dissolution of language without impairment of other cognitive
      domains for at least the first 2 years of illness (M.-M. Mesulam, 1982, 2001). It
      is difficult to demonstrate the integrity of nonlanguage domains in PPA because
      most neuropsychological tests of memory, reasoning, and attention require
      language competence for their performance. In the present study, reasoning and
      cognitive flexibility were tested nonverbally in patients with PPA using a
      modified ten-item version of the Visual Verbal Test (Feldman & Drasgow, 1959).
      This test measures the ability to detect similarities among objects and to sort a
      single set of objects according to two different principles. The performance of
      PPA patients (n = 20) was compared with that of patients with dementia of the
      Alzheimer type (AD) (n = 20), patients with the comportmental/executive
      dysfunction variant of frontotemporal dementia (FTD) (n = 16), and cognitively
      intact controls (n = 20). Patients with PPA and controls performed similarly,
      detecting commonalities among objects and shifting from one sorting principle to
      another. In contrast, both AD and FTD subjects were significantly impaired on
      both measures. These results provide evidence of preserved reasoning in PPA,
      further differentiating this syndrome from other behaviorally focal dementia
      syndromes.

PMID- 15512926
TI  - Functional brain asymmetries during visuomotor tracking.
AB  - This study examined brain asymmetries elicited during visuomotor tracking. Thirty
      two healthy participants performed a fixed gaze, dynamic, pinch force, visuomotor
      tracking task during a functional magnetic resonance imaging study. The dynamic
      task required the subject to press a rubber bulb with the thumb to trace a cosine
      square wave varying in force amplitude from 0-500 cN and having a frequency of
      1.5 Hz. Response hand order and direction of the stimulus presentation (right-to
      left or left-to-right) were permuted across participants. Two forms of functional
      cerebral asymmetry were observed, hemispheric specialization and homologous
      lateralized response. The superior portion of the right middle frontal gyrus and
      the left supplementary motor area appeared specialized for VM tracking regardless
      of response hand used or stimulus movement direction. Lateralized effects
      appeared in the primary sensorimotor hand area, putamen, parietal
      operculum/posterior insula, dentate nucleus of the cerebellum, precuneus, and
      middle occipital gyrus. These lateralized areas of activation surfaced when
      either response hand or direction of stimulus movement was manipulated. The VM
      task used in this study activated asymmetrical neural activity in the vertically
      organized skelotomotor system and in sensory systems involving visual attention
      or proprioception.

PMID- 15512927
TI  - Medically unexplained symptoms and neuropsychological assessment.
AB  - Several illnesses expressed somatically that do not have clearly demonstrated
      pathophysiological origin and that are associated with neuropsychological
      complaints are reviewed. Among them are nonepileptic seizures, fibromyalgia,
      chronic fatigue syndrome, Persian Gulf War unexplained illnesses, toxic mold and
      sick building syndrome, and silicone breast implant disease. Some of these
      illnesses may be associated with objective cognitive abnormalities, but it is not
      likely that these abnormalities are caused by traditionally defined neurological
      disease. Instead, the cognitive abnormalities may be caused by a complex
      interaction between biological and psychological factors. Nonepileptic seizures
      serve as an excellent model of medically unexplained symptoms. Although
      nonepileptic seizures clearly are associated with objective cognitive
      abnormalities, they are not of neurological origin. There is evidence that severe
      stressors and PTSD are associated with immune system problems, neurochemical
      changes, and various diseases; these data blur the distinctions between
      psychological and organic etiologies. Diagnostic problems are intensified by the
      fact that many patients are poor historians. Patients are prone to omit history
      of severe stressors and psychiatric problems, and the inability to talk about
      stressors increases the likelihood of suffering from physiological forms of
      stress.

PMID- 15512928
TI  - The relationship of behavioral inhibition to executive functions in young adults.
AB  - Barkley's hybrid model of executive functions (EFs) predicts that individuals
      with deficient inhibitory control should show impairment of EFs. Thirty-eight
      nonreferred young adults were administered tests of EFs and four laboratory
      measures of inhibitory control: Stop Signal (SS), Go No-Go, Competing Motor
      Program (CMP), and Stroop Color-Word tests. Behavioral ratings of impulsivity
      were collected using the Barratt Impulsivity Scale-11 (BIS-11). CMP and SS
      accounted for a significant proportion of variance in measures of EFs beyond that
      accounted for by IQ. Additionally, increased impulsivity, as measured by the BIS
      11, was associated with poorer performance on some tests of EFs. These findings
      provide partial support for Barkley's theory in that effective executive
      functioning is associated with sufficient inhibitory control.

PMID- 15512929
TI  - Explicit and objective scoring criteria for the taylor complex figure test.
AB  - The Rey and Taylor figures are two constructional and visual memory tests used
      interchangeably. The purpose of this study was to develop a scoring system for
      the Taylor figure based on the explicit guidelines established by Meyers and
      Meyers (1995) for the Rey figure. Younger (n = 97; mean age = 21 years) and older
      (n = 61; mean age = 72 years) participants' performance on the Taylor figure was
      scored according to the proposed scoring system and the original scoring system
      devised by Taylor (1989). Both scoring systems yielded comparable scores on the
      Taylor figure as well as comparable patterns of validity and good interrater
      reliabilities (0.85-0.98). Although the present system does not further improve
      scoring reliability, it renders both tests similar in methodology and simplifies
      training to evaluate the two figures. The present study also reveals the
      limitations of the use of the Taylor and the Rey in test-retest situations but
      suggests that administering the Taylor first would improve the comparability of
      the two figures in a test-retest situation.

PMID- 15512930
TI  - Exaggeration index for an expanded version of the auditory verbal learning test:
      robustness to coaching.
AB  - Recent research suggests that effort detection measures based on patterns of
      neuropsychological performance may be more robust to coaching than traditional
      effort detection measures. In the present study, we evaluated the Exaggeration
      Index for an extended version of the Auditory Verbal Learning Test (EI-AVLTX), a
      recently developed effort detection instrument based on patterns of performance
      on the AVLT using a simulated malingering paradigm. In two independent samples,
      the EI-AVLTX was1 found to be relatively sensitive and specific to malingering,
      and robust to the effects of a warning about malingering detection.

PMID- 15512931
TI  - Aging, recall and recognition: a study on the sensitivity of the University of
      Southern California Repeatable Episodic Memory Test (USC-REMT).
AB  - This study examines the sensitivity of the University of Southern California
      Repeatable Episodic Memory Test (USC-REMT) to the effects of aging in a sample of
      112 men and women from 18 to 93 years old. Two new recognition measures, yes-no
      and forced-choice, were developed to supplement the original USC-REMT which
      measured only free-recall. Free-recall, yes-no recognition and forced-choice
      recognition were sensitive to age effects, with free-recall being the most
      sensitive. The seven recall and recognition lists can be used interchangeably.
      The data indicate that the USC-REMT is worthy of consideration when there is a
      need for a brief, screening tool of various memory functions, particularly when
      there is interest in memory changes over time and repeated assessments.

PMID- 15512932
TI  - Frontal lobe damage and tests of executive processing: a meta-analysis of the
      category test, stroop test, and trail-making test.
AB  - The Category Test, Trails B, and the interference task of the Stroop Test are
      among the most commonly administered measures of frontal lobe functioning and are
      thought to tap different cognitive functions mediated by these brain regions. Two
      meta-analyses were conducted on these tests to determine their sensitivity to
      frontal and lateralized frontal brain damage. Study 1 compared participants with
      frontal lobe damage to those with damage to posterior brain regions, whereas
      Study 2 compared participants with left and right frontal lobe damage. For each
      study, effect sizes based on performance differences between the above groups
      were calculated for the Category Test, Trail-Making Test Parts A and B, and the
      Stroop Test, including Word, Color, and Color-Word subtests. In Study 1
      significant differences between groups were found for Trails A and all Stroop
      tasks, but in Study 2 the only difference between left and right frontal
      participants was on the Stroop Color-Word task. Potential reasons why Trails A
      and the Stroop Test are sensitive to frontal lobe damage are discussed, such as
      novelty and processing speed, as are clinical implications of these findings. The
      challenges of research on assessment of frontal lobe functioning are discussed
      and new developments in this area are highlighted.

PMID- 15512934
TI  - A new look at the WMS-III: new research to guide clinical practice.
AB  - The Wechsler Memory Scale, Third Edition (WMS-III) was published in 1997 and
      marked an ambitious and substantial revision of the traditional memory scale.
      Since publication, however, clinical experience has led many practitioners to
      raise questions about the validity and clinical utility of the new subtests and
      new index scores. The impetus of this special issue was to address some of the
      questions with which clinicians have been struggling. The articles contained in
      this special issue present new empirical research on the WMS-III, and several
      include new methods and scoring techniques that go beyond what has been published
      in the WAIS-III-WMS-III Technical Manual (The Psychological Corporation, 1997,
      2002). It is hoped that the new scores and techniques will prove useful in
      clinical practice and that this research will benefit future revisions of the
      Wechsler Memory Scale.

PMID- 15512935
TI  - Parsing the recognition memory components of the WMS-III face memory subtest:
      normative data and clinical findings in dementia groups.
AB  - The WMS-III face memory subtest was developed as a quick, reliable, measure of
      non-verbal recognition memory. While the face memory subtest has demonstrated
      clinical sensitivity, the test has been criticized for low correlation with other
      WMS-III visual memory subtests and for failing to differentiate performance
      between clinical groups. One possible reason for these findings may be due to the
      impact of response bias associated with recognition memory tests. Four studies
      were conducted to evaluate the utility of applying signal detection measures to
      the face memory subtests. The first two studies used the WMS-III standardization
      data set to determine age and education effects and to present normative and
      reliability data for hits, false positives, discriminability and response bias.
      The third study tested the hypothesis that using response components and signal
      detection measures would enhance the correlation between face memory and the
      other WMS-III visual memory subtests. The fourth study compared performance of
      patients with Alzheimer's disease, Huntington's disease, Korsakoff's syndrome and
      demographically matched controls on the new face memory scores. The new measures
      did not have higher correlation with other WMS-III visual memory measures than
      the standard scoring of the test. Analysis of the clinical samples indicated that
      the discriminability index best differentiated patients from controls. The
      response components, particularly delayed false positives, differentiated
      performance among the clinical groups. Normative and reliability data are
      presented.

PMID- 15512936
TI  - Validation of the WMS-III Facial Memory subtest with the Graduate Hospital Facial
      Memory Test in a sample of right and left anterior temporal lobectomy patients.
AB  - A number of studies have shown visuospatial memory deficits following anterior
      temporal lobectomy (ATL) in the right, nondominant temporal lobe (RATL). The
      current study examines 26 patients with intractable temporal lobe epilepsy who
      underwent ATL in either the right (RATL, n = 16) or left temporal lobe (LATL, n =
      10) on two tests of facial memory abilities, the Wechsler Memory Scale-III (WMS
      III) Faces subtest and the Graduate Hospital Facial Memory Test (FMT). Repeated
      measures ANOVA on the FMT indicated a significant main effect of side of surgery.
      The RATL group performed significantly below the LATL group overall. Both groups
      showed a slight, but non-significant, improvement in performance from pre- to
      postsurgery on the FMT immediate memory, likely due to practice effects. Repeated
      measures ANOVA on the WMS-III Faces subtest revealed a significant interaction of
      group (RATL vs. LATL) by delay (immediate vs. delayed). Overall, the LATL group
      showed an improvement in recognition scores from immediate to delayed memory,
      whereas the RATL group performed similarly at both immediate and delayed testing.
      No effects of surgery were noted on the WMS-III. Following initial data analysis
      the WMS-III Faces I and II data were re-scored using the scoring suggested by
      Holdnack and Delis (2003), earlier in this issue. Repeated measures ANOVA
      revealed a trend toward significance in the three-way interaction of group (RATL
      vs. LATL) x time of testing (pre- versus postop) x delay (immediate vs. delayed
      memory). On the Faces I subtest, both the RATL and LATL groups showed a decline
      from preoperative to postoperative testing. However, on Faces II the LATL group
      showed an increase in performance from preoperative to postoperative testing,
      while the RALT group showed a decline in performance from preoperative to
      postoperative testing. While the FMT appears to be superior to the WMS-III Faces
      subtest in identifying deficits in facial memory prior to and following RATL, the
      application of the scoring methodology presented by Holdnack and Delis earlier in
      this issue does serve to increase the clinical utility of the WMS-III Faces
      subtest in this population.

PMID- 15512937
TI  - Replacement of the Faces subtest by Visual Reproductions within Wechsler Memory
      Scale-Third Edition (WMS-III) visual memory indexes: implications for discrepancy
      analysis.
AB  - Within discrepancy analysis differences between scores are examined for
      abnormality. Although larger differences are generally associated with rising
      impairment probabilities, the relationship between discrepancy size and
      abnormality varies across score pairs in relation to the correlation between the
      contrasted scores in normal subjects. Examinee ability level also affects the
      size of discrepancies observed normally. Wechsler Memory Scale-Third Edition (WMS
      III) visual index scores correlate only modestly with other Wechsler Adult
      Intelligence Scale-Third Edition (WAIS-III) and WMS-III index scores;
      consequently, differences between these scores and others have to be very large
      before they become unusual, especially for subjects of higher intelligence. The
      substitution of the Faces subtest by Visual Reproductions within visual memory
      indexes formed by the combination of WMS-III visual subtests (creating immediate
      recall, delayed recall, and combined immediate and delayed index scores) results
      in higher correlation coefficients, and a decline in the discrepancy size
      required to surpass base rate thresholds for probable impairment. This gain
      appears not to occur at the cost of a diminished sensitivity to diverse
      pathologies. New WMS-III discrepancy base rate data are supplied to complement
      those currently available to clinicians.

PMID- 15512938
TI  - The family pictures test as a measure of impaired feature binding in
      schizophrenia.
AB  - We investigated the use of the Family Pictures test from the Wechsler Memory
      Scale III as a measure of the ability to bind the multiple features of a complex
      visual scene in a study group of 77 patients with schizophrenia and 44 healthy
      controls. Patients demonstrated impaired recall of all scene features as well as
      a reduction in the number of features recalled for each remembered character.
      Secondary analyses using patients and controls matched for character recall also
      showed reduced feature binding in the patient group. Such feature binding
      deficits likely implicate hippocampal dysfunction, consistent with neuroimaging
      evidence of structural and functional compromise of the medial temporal lobe in
      schizophrenia.

PMID- 15512939
TI  - Qualitative analysis of WMS-III Logical Memory and Visual Reproduction in
      temporal lobe epilepsy.
AB  - Clinical observation of performance on the Logical Memory (LM) and Visual
      Reproduction (VR) subtests from the WMS-III has revealed some variability in
      retention rates across stories and figures. This paper examined the degree to
      which this variability occurs in lateralized temporal lobe epilepsy (TLE) in
      comparison to a matched group from the WMS-III standardization sample, and
      explored whether analysis of qualitative aspects of LM and VR performance yield
      additional lateralizing information in TLE. Analysis of LM and VR scaled scores
      revealed differences between the TLE groups for LM, but not VR scores. All
      subjects benefited from repetition of LM Story B, with greater improvement in
      story retention in the Left versus Right TLE group. Variability in VR recall
      across figures was seen in all groups, with a bimodal distribution of retention
      rates for each figure and a sizable percentage of each group completely
      forgetting two or more figures. These results suggest that more careful analysis
      of individual LM story performance may be useful in some patients with TLE,
      whereas variability in VR retention across figures is common and should not be
      over interpreted.

PMID- 15512940
TI  - Age-associated memory impairment of Logical Memory and Visual Reproduction.
AB  - The standardization sample from the WMS-III (weighted N = 1250) (The
      Psychological Corporation, 1997; Tulsky & Ledbetter, 2000), which varied in age
      from 16 to 89, was used to determine whether storage of verbal and spatial
      information was affected by normal aging. A previous study with the same sample
      using an analysis of variance approach showed that the age-associated
      deterioration for Logical Memory (LM) and Visual Reproduction (VR) delayed recall
      and recognition were comparable and largely explained by poor immediate recall.
      This led to the conclusion that age-associated memory impairment was due
      primarily to encoding deficits. However, that study did not control for the age
      associated deterioration in immediate recall in order to ensure that the small
      age-associated effects for delayed recall and recognition were not confounded by
      the fact that the elderly had less to remember on the delayed recall and
      recognition trials. The current study used covariance analysis to statistically
      adjust the dependent measures, LM and VR delayed recall and recognition, based on
      immediate recall scores. These analyses showed that the age-associated changes in
      these measures were statistically significant, but the effect sizes were very
      small. Partial eta(2) for the main effect of age for LM was 0.06 with weak effect
      sizes for the interaction of recall type and age (0.02). The partial eta(2) for
      the main effect of age for VR was 0.09, and the interaction of recall type and
      age (0.04). This pattern of findings shows that after adjustment for immediate
      recall, LM and VR recall and recognition demonstrated comparable, slight declines
      with age suggesting that normal aging produced minimal changes in the ability to
      store new information when age-associated changes in initial encoding and
      retrieval were statistically controlled.

PMID- 15512941
TI  - Memory span on the Wechsler Scales.
AB  - This study had two goals. One was to assess whether the WMS-III Spatial Span
      subtest operates as a visual analogue of Digit Span while the second was to
      determine whether backward span is a more sensitive measure of working memory
      than the forward span condition. Analyses based on the WAIS-III-WMS-III
      standardization and clinical group data revealed some important distinctions
      between Digit and Spatial Span. The two tasks exhibited differences in patterns
      of performance on the forward versus backward conditions, in their relationships
      with age, and in their methodology. Moreover, the backward conditions of both
      Digit and Spatial Span did not appear more affected by risk factors such as aging
      or pathology than the forward scores. This runs contrary to the widespread notion
      that backward span provides differential sensitivity regarding working memory
      processing.

PMID- 15512942
TI  - Is speed of processing or working memory the primary information processing
      deficit in multiple sclerosis?
AB  - OBJECTIVE: To examine whether processing speed or working memory is the primary
      information processing deficit in persons with MS. DESIGN: Case-control study.
      SETTING: Hospital-based specialty clinic. PARTICIPANTS: 215 adults with
      clinically definite MS. MAIN OUTCOME MEASURE: Mean demographically corrected T
      scores, prevalence rates of impairment and relative risk of impaired Processing
      Speed and Working Memory Index Scores from the WAIS-WMS III. RESULTS: Deficits in
      Processing Speed were much more common than Working Memory in all comparisons.
      This was observed for both relapsing remitting (RRMS) and secondary progressive
      MS (SPMS) subjects, but accentuated in the latter group. CONCLUSIONS: Results
      strongly suggest that the primary information processing deficit in persons with
      MS is in speed of processing.

PMID- 15512943
TI  - Development of a new Delayed Memory Index for the WMS-III.
AB  - This paper presents the Delayed Memory Index (DMI) as an alternative to the
      General Memory Index (GMI) of the Weschler Memory Scale-Third Edition (WMS-III).
      The WMS-III Immediate Memory Index (IMI) and the GMI are not parallel in
      structure, making a direct comparison between these index scores (i.e., immediate
      vs. delayed memory variables) difficult. The IMI is composed of the sum of scaled
      scores of four subtests (Logical Memory I, Verbal Paired Associates I, Faces I,
      and Family Pictures I) while the GMI is composed of the sum of scaled scores of
      five subtests (Logical Memory II, Verbal Paired Associates II, Faces II, Family
      Pictures II and Auditory Recognition Delayed). Inclusion of Auditory Recognition
      Delayed in the GMI is also problematic as it is highly skewed and limited by
      extreme ceiling effects (see Tulsky, Chiaravalloti, Palmer, & Chelune, 2003). To
      remedy these problems, we present a new index score that does not include
      auditory recognition, the Delayed Memory Index. Normative tables for the new
      Delayed Memory Index based on the inclusion of the Faces subtest, or
      alternatively the Visual Reproduction subtest, are presented, and initial
      estimates of their psychometric properties are described.

PMID- 15512945
TI  - Correlation of retinal function with retinal histopathology following ischemia
      reperfusion in rat eyes.
AB  - PURPOSE: To investigate the relationship between retinal function and
      histopathology following retinal ischemia-reperfusion in rats. METHODS: Retinal
      ischemia was induced in 27 Sprague-Dawley rats by raising the intraocular
      pressure for 60- or 90-minutes. Two weeks after the retinal ischemia-reperfusion,
      ganzfeld stimuli of different luminances (maximum 0.51 log cd-s/m2) were used to
      elicit full-field ERGs from the right (experimental) and left (control) eyes. The
      amplitudes of the scotopic b-waves were measured, and intensity-response curves
      were plotted. The b-wave amplitudes at the initial peak (VbIP), the dip
      (Vb(dip)), and the maximum stimulus intensity (Vb(max)) were measured. The
      animals were sacrificed after the ERG recordings to determine the surviving
      retinal cells in the inner nuclear layer (INL). RESULTS: The log values of the
      VbIP, Vb(dip) and Vb(max) were linearly correlated with the number of surviving
      cells in the INL (r = 0.928, 0.905, and 0.913 for VbIP, Vb(dip) and Vb(max),
      respectively; p < 0.0001 for each). The slope of the regression line for the
      Vb(dip) was significantly steeper than that for the VbIP and Vb(max) (p < 0.005).
      The regression line for the Vb(dip) reached undetectable level of the b-wave (<1
      microV) even though approximately 25% of the cells still remained in the INL.
      CONCLUSIONS: The amplitude of the scotopic b-wave is a sensitive index of the
      surviving INL cells. However, if one selects the stimulus intensity at the dip,
      the functional loss would be exaggerated in spite of the presence of cells in the
      INL.

PMID- 15512944
TI  - Microarray analysis identified differentially expressed genes in keratocytes from
      keratoconus patients.
AB  - PURPOSE: To identify differentially expressed genes in human keratoconus
      keratocyte by cDNA microarray. METHODS: Normal and keratoconic cornea were
      cultured for keratocytes. RNA was extracted. cDNA probe labeled with fluorescence
      dye was made from Poly A+ RNA, hybridized with microarray slide, containing 164
      human apoptosis genes. Signal intensity was measured. Expression ratio between
      keratoconus and normal was determined using ImaGene Ver.3.0. Identified genes
      were further evaluated by RT-PCR and real-time PCR. RESULTS: Five over-expressed
      and four under-expressed genes were identified. Of these, differential expression
      of tumor necrosis factor alpha-induced protein 6 (TNFAIP6), human insulin-like
      growth factor binding protein 5 (IGFBP5), and IGFBP3 were verified and confirmed
      by RT-PCR. Real-time PCR showed TNFAIP6 increased by 3.3 folds, while IGFBP5,
      IGFBP3 decreased by 14 and 11 folds respectively. CONCLUSIONS: The identified
      genes could be important and deserve further investigation. Significant
      differential expression of TNFAIP6, IGFBP5, and IGFBP3 may indicate an important
      role of these genes in the mechanism underlying stromal thinning.

PMID- 15512946
TI  - Effect of hydrostatic pressure gradients and Na2EDTA on permeability of human
      Schlemm's canal cell monolayers.
AB  - PURPOSE: Elevated intraocular pressure in those with glaucoma appears to be a
      function of increased resistance to movement of aqueous humor through the
      conventional outflow pathway. The majority of resistance in both normal and
      glaucomatous eyes is generated in the region between the juxtacanalicular
      trabecular meshwork and the inner wall of Schlemm's canal. To accommodate
      transient elevations in pressure, we hypothesize that conventional outflow
      increases rapidly due to changes in complexity of intercellular junctions between
      cells of the inner wall of Schlemm's canal. METHODS: To test this hypothesis we
      examined specifically the effects of hydrostatic pressure gradients and the
      calcium chelator, Na2EDTA, on permeability of cultured human Schlemm's canal cell
      monolayers in isolation. Human Schlemm's Canal cells were isolated, cultured and
      then seeded onto permeable supports and maintained in culture to allow
      intercellular junctions to mature. With a minimum net transendothelial electrical
      resistance of 10 Ohm cm2, cells were placed into an Ussing-type chamber and
      hydraulic conductivity was calculated from pressure and flow measurements that
      were continuously recorded. Simultaneously, transendothelial electrical
      resistance was measured manually at fixed intervals. In parallel experiments,
      cell margins were monitored in real time by videomicroscopy. RESULTS: During the
      baseline measurement period when cells were exposed to pressure but not Na2EDTA,
      hydraulic conductivity was constant but transendothelial electrical resistance
      decreased continuously at rate of 0.24 Ohm cm2/minute. After Na2EDTA treatment,
      no significant change in transendothelial electrical resistance was measured
      while, hydraulic conductivity of Schlemm's Canal monolayers increased
      significantly by 125%; corresponding to noticeable intercellular separations.
      Restoration of cell-cell contact was observed by videomicroscopy 30 minutes
      following washout of Na2EDTA and functionally after 2 hours. CONCLUSIONS:
      Responses of Schlemm's Canal cells to pressure and calcium chelators in vitro are
      consistent with a role for calcium sensitive junctions in outflow resistance in
      vivo.

PMID- 15512947
TI  - Iron chelation abrogates excessive formation of hydroxyl radicals and lipid
      peroxidation products in monocytes of patients with Eales' disease: direct
      evidence using electron spin resonance spectroscopy.
AB  - PURPOSE: Eales' disease (ED) is an idiopathic retinal vasculitis condition, which
      affects the retina of young adult males. Retinal changes include perivasculitis,
      non-perfusion and neovascularization. Disruption of blood-retinal barrier (BRB)
      is the common feature in intra-ocular inflammatory diseases. Disruption of BRB
      results in vascular hyper permeability and infiltration of circulating leukocytes
      into the retinal parenchyma. Monocyte (MC) activation results in oxidant thrust
      and subsequent tissue damage. This has been reported in various intra-ocular
      inflammatory diseases such as uveitis and Behcet's disease. However, there are no
      such reports available in ED. Hence in the present study we have investigated the
      role of MC activation and hydroxyl radicals (OH) production and its possible
      involvement in promoting the development of retinal vasculitis in patients with
      ED. METHODS: Twelve patients with ED and twelve healthy volunteers were recruited
      for the study. MC was separated from their peripheral blood. MC from patients
      with ED and control subjects was stimulated with phorbol-12-myristate-acetate
      (PMA) and OH generated was analyzed using an electron spin resonance spectrometer
      (ESR). Superoxide dismutase (SOD), thiobarbituric acid reactive substances
      (TBARS), and iron content was determined in MC to assess the oxidant thrust and
      antioxidant defense. RESULTS: OH generation was elevated in MC from patients with
      ED, which coincided with diminished SOD activity and elevated levels of iron and
      TBARS, when compared with healthy control subjects. OH generation was abrogated
      when MC from ED were co-incubated with PMA and iron chelators such as
      diethylenetriaminepentacetic acid (DTPA) and desferrioxamine. Iron chelation also
      inhibited TBARS accumulation restored SOD activity in MC of patients with ED.
      CONCLUSIONS: For the first time we have demonstrated the production of OH
      generation in MC of patients with ED using ESR. Further we have shown the
      beneficial effect of iron chelation in mitigating free radical mediated changes
      in cellular metabolism. Based on our findings, we provide further evidence for
      the role of oxidant thrust in promoting retinal tissue damage in patients with
      ED.

PMID- 15512948
TI  - HLA expression in choroidal melanomas: correlation with clinicopathological
      features.
AB  - PURPOSE: In this retrospective study, we analyzed the relevance of human
      leukocyte antigen (HLA) expression to clinical behavior of uveal melanoma and
      correlated it with conventional light microscopic parameters. METHODS: HLA class
      I antigen and Beta 2 microglobulin expression were analyzed in 45 primary
      choroidal melanoma lesions by immunoperoxidase staining with monoclonal
      antibodies to HLA class I antigen and beta 2 microglobulin and correlated with
      the known clinicopathological parameters. Immunoanalysis was done by a semi
      quantitative method. The tumors were divided into 3 groups. Group A: Tumors with
      no extrascleral extension/no liver metastases, group B: tumors with only
      extrascleral extension and group C: tumors with liver metastases. For statistical
      analysis we analyzed the negative, weak (heterogeneous) and the positive
      expression of HLA and beta 2 microglobulin with known clinicopathological
      parameters. RESULTS: In-group A (n = 35) tumors with no extrascleral extension
      and no liver metastases HLA class I antigen and beta 2 microglobulin are negative
      (absent staining) in 30 choroidal melanomas. In-group B (n = 4) they are weak
      (heterogeneous) in 3 tumors. In-group C (n = 6) all the 6 tumors have a positive
      (bright staining) immunoexpression. No statistical significance was obtained when
      HLA and beta 2 microglobulin immunoreactivity was compared against largest tumor
      diameter (LTD), tumor infiltrating lymphocytes (TIL), mitosis and nuclear grade.
      The difference of HLA class I and beta 2-microglobulin imunoreactivity among the
      various cell types spindle, mixed and epithelioid was statistically significant
      (p = 0.003), (p = 0.004). The difference in immunoreactivity between tumors with
      no liver metastases and tumors with liver metastases was statistically
      significant (p < 0.001). CONCLUSIONS: HLA class I antigen and beta 2
      microglobulin are negative in melanomas with no extrascleral extension and liver
      metastases and weak in melanomas with extrascleral extension and are positive in
      melanomas with liver metastases. HLA expression is independent of the
      conventional markers in uveal melanoma.

PMID- 15512949
TI  - Tear chymase in vernal keratoconjunctivitis.
AB  - PURPOSE: To determine the levels of mast cell chymase and tryptase activity in
      the tears of patients with vernal keratoconjunctivitis (VKC). METHODS: Subjects
      were 38 VKC patients and 18 healthy controls whose chymase and tryptase activity
      in tears was measured by enzyme assay. VKC severity was quantified based on the
      following clinical signs: papillary hypertrophy, conjunctival hyperemia, edema,
      punctate keratitis, Trantas dots, and mucus production. Of the 38 VKC patients,
      the degree of disease severity was mild in 13, moderate in 18, and severe in 7.
      RESULTS: Mean chymase activity and standard deviation in tears was 0.23+/-0.07mU
      in mild VKC, 0.68+/-0.22mU in moderate VKC, 1.91+/-0.71 mU in severe VKC, and
      0.11+/-0.05 mU in healthy controls. The increase in all VKC stages was
      statistically significant compared to that in healthy control. The degree of
      chymase activity in tears correlated significantly with VKC severity (r = 0.9245,
      p < 0.001). High tryptase activity was also detected in the tears of VKC
      patients, although increased tryptase activity in tears did not correlate with
      disease severity (r = 0.1999). CONCLUSIONS: Chymase activity in tears may thus be
      a sensitive marker for determining the severity of VKC.

PMID- 15512950
TI  - Mouse model of post-surgical breakdown of the blood-retinal barrier.
AB  - PURPOSE: Post-surgical macular edema is an important clinical problem resulting
      from breakdown of the blood-retinal barrier (BRB) after surgery. This study was
      designed to develop a mouse model of post-surgical BRB breakdown. METHODS: Two 25
      gauge needles, one for infusion and one for aspiration, were inserted through the
      limbus and into the lens of one eye of adult male C57BL/6 mice. The anterior
      portion of the lens was aspirated and the fellow eye was untreated. At several
      time points after surgery, the integrity of the BRB was assessed quantitatively,
      using [3H]mannitol as a tracer, or qualitatively, using immunohistochemical
      staining for albumin. RESULTS: Eyes with partial lens extraction had a
      significant increase in retinal vascular leakage one day after surgery, which
      persisted two and three days after surgery, but by five days, was not
      significantly different from controls. Immunohistochemical staining for albumin
      demonstrated that the breech in the barrier was sufficient to allow passage of a
      60kDa protein into the retina, and was localized predominantly to retinal
      vessels. CONCLUSIONS: Partial lens extraction in mice results in BRB breakdown
      (primarily the inner BRB) that is highly reproducible in the severity of leakage
      and its time course. This provides a valuable tool for investigation of the
      molecular pathogenesis and new treatment approaches for post-surgical breakdown
      of the BRB.

PMID- 15512951
TI  - CD200 maintains microglial potential to migrate in adult human retinal explant
      model.
AB  - PURPOSE: Retinal microglia (MG) migrate in response to injury, degeneration and
      inflammation dependent upon both soluble and cognate signals they receive.
      Previously we found that lipopolysaccharide/interferon-gamma (LPS/IFNgamma)
      stimulation induces a paradoxical IL-10 mediated suppression of MG migration from
      retinal explants. Given the high expression of neuronal CD200, which can induce
      down regulation of CD200 receptor-positive MG activation and neuronal fractalkine
      expression potentially stimulating MG migration, we wished to further examine
      their respective roles in the maintenance of MG activation and migration.
      METHODS: A human retinal explant model of MG migration was used. CD200 receptor
      and fractalkine receptor stimulation was achieved by addition to explants of
      CD200:Fc fusion protein and recombinant cytokine respectively, with or without
      LPS-IFNgamma stimulation that is known to suppress migration. Cell migration and
      cell activation (iNOS expression) was counted and assessed by numbers of CD45+
      cells by immunofluorescence and standardised flow cytometric bead array analysis
      was performed for cytokine production. RESULTS: Retinal explants expressed
      fractalkine and CX3CR1 immunohistochemically and by PCR. Addition of Fractalkine
      and not CD200:Fc induced MG migration from retinal explants. However LPS/IFNgamma
      induced suppression of MG migration could only be restored in the presence of
      CD200:Fc, whilst MG remained iNOS-negative and generated IL-10. CONCLUSIONS:
      Microglial responses are tightly governed within retina. Although MG do not
      classically activate following LPS/IFNgamma stimulation, their migration is
      sustained via CD200R stimulation maintaining their potential to migrate in
      response to injury.

PMID- 15512952
TI  - Pre-clinical investigation of the efficacy of an artificial tear solution
      containing hydroxypropyl-guar as a gelling agent.
AB  - PURPOSE: Pre-clinical studies of a new artificial tear product (Systane
      Lubricating Eye Drops Alcon Laboratories, Inc., Fort Worth, TX) containing the
      novel gelling agent hydroxypropyl-guar (HP-guar) and two demulcents, polyethylene
      glycol 400 (PEG) and propylene glycol (PG) were conducted to determine the
      ability of the product to protect ocular surface epithelial cells from
      desiccation in vivo and in vitro, and to promote recovery of the damaged corneal
      epithelial barrier in vivo. Other leading artificial tear products were also
      evaluated as comparators to determine the relative effectiveness of different
      polymer systems. METHODS: Damage due to desiccation was assessed by measuring
      corneal uptake of methylene blue compared to untreated corneas. Corneas of
      anesthetized rabbits were treated with the new artificial tear product and
      subjected to desiccation by holding the eyelids open for 2 hours with a speculum.
      Control eyes were subjected to desiccation without application of a tear
      formulation. To measure recovery of the corneal epithelium from damage, corneas
      of anethesthetized rabbits were exposed to 0.01% benzalkonium chloride (BAC) for
      5 minutes to increase epithelial permeability. The corneas were exposed to the
      new artificial tear for 1.5 hours followed by measurement of uptake of 5,6
      carboxyfluorescein (CF). In the desiccation and CF uptake experiments, the new
      tear product was also compared to a tear product formulation without HP-guar and
      to a commercially available artificial tear containing carboxymethyl cellulose
      (CMC) and Purite. In a third set of experiments, immortalized human corneal
      epithelial cells and Chang conjunctival cells in culture were exposed to the
      PEG/PG/HP-guar tear product, the control formulation without HP-guar, a tear
      formulation preserved with BAC, or the artificial tear containing CMC/Purite for
      15min. The tear formulation was removed and the cells were exposed to desiccating
      conditions in a laboratory safety hood for 10 or 30min. Cell viability was
      determined using the MTT assay. RESULTS: The in vivo desiccation model, showed
      that the new tear product, Systane, offered complete protection of the cornea
      from desiccation (methylene blue uptake not different than naive control).
      Following exposure to 0.01% BAC, the new artificial tear product also provided an
      environment in which the corneal epithelium recovered completely from damage (CF
      uptake not different than normal, untreated cornea). This level of protection was
      not observed when corneas were treated with other formulations. Results from the
      in vitro desiccation procedure indicated that viability of corneal epithelial and
      Chang cells treated with the PEG/PG/HP-guar product was significantly greater
      than viability of cells treated with the tear product without HP-guar or the tear
      products containing BAC or CMC/Purite. CONCLUSIONS: The tear product containing
      HP-guar, PEG 400 and propylene glycol satisfies several pre-clinical criteria for
      an appropriate artificial tear formulation. It gives long-term desiccation
      protection of the intact cornea and also epithelial cells in culture and has no
      apparent deleterious affects on cells. It also provides conditions in which a
      damaged corneal epithelium can recover normal barrier function. The combination
      of ingredients in the formulation appears to provide an effective mucomimetic
      artificial tear product. These pre-clinical data suggest that the product will be
      effective in providing superior relief for the dry eye sufferer.

PMID- 15512953
TI  - Rapid and sensitive diagnosis of adenoviral keratoconjunctivitis by loop-mediated
      isothermal amplification (LAMP) method.
AB  - PURPOSE: To develop a new method to detect and type adenoviruses directly from
      conjunctival scrapings using loop-mediated isothermal amplification (LAMP) with
      adenovirus (ad) type specific primer. METHODS: Using primers specific for the
      gene of ad1, ad3, ad4, ad8, ad19 and ad37, heat denatured adenovirus DNA was
      amplified by the LAMP and polymerase chain reaction (PCR). Alkaline lysed
      adenovirus prototype and conjunctival scrapings were also used directly as
      templates. RESULTS: Type specific primers amplified ad genes of the corresponding
      ad prototype specifically. The specific amplification was observed in both heat
      denatured and alkaline lysed samples. The amplified product was first detected
      within 45 min. Ad genotypes of clinical samples determined by the LAMP method
      were almost identical to those determined using the PCR-sequencing method.
      CONCLUSIONS: LAMP based isothermal amplification of adenovirus genome for
      detection and typing of adenoviruses is faster than PCR based methods. This new
      method will be useful for rapid diagnosis and typing of adenoviral
      conjunctivitis.

PMID- 15512955
TI  - Ocular and neuronal cell apoptosis during HSV-1 infection: a review.
AB  - HSV-1 may activate or suppress the apoptotic pathway in various cells. This
      review will discuss this apparent dichotomy and place particular emphasis on the
      different strategies HSV-1 uses to block or suppress the apoptotic pathway in
      various cell lines and tissues.

PMID- 15512956
TI  - AIDS-related cytomegalovirus retinitis: lessons from the laboratory.

PMID- 15512957
TI  - Virulence genes in herpes simplex virus type 1 corneal infection.

PMID- 15512958
TI  - Acetylsalicylic acid reduces viral shedding induced by thermal stress.
AB  - PURPOSE: To investigate the effect of acetylsalicylic acid on ocular shedding of
      herpes simplex virus type 1 (HSV-1). MATERIALS AND METHODS: Mice that were latent
      for the McKrae strain of HSV-1 were treated with acetylsalicylic acid, a
      nonspecific inhibitor of cyclooxygenases, either prophylactically or at the time
      of heat stress-induced viral reactivation. The effect of the drug on viral
      shedding in the tear film, infectious virus in the cornea and trigeminal
      ganglion, and viral DNA in the cornea and trigeminal ganglion was determined.
      RESULTS: Acetylsalicylic acid inhibited heat stress-induced shedding of virus in
      the tears and reduced the numbers of corneal and trigeminal ganglion homogenates
      containing virus. Intraperitoneal therapeutic and oral prophylactic plus
      therapeutic treatments were similar in their ability to inhibit reactivation.
      CONCLUSIONS: The results indicate that a cyclooxygenase inhibitor such as
      acetylsalicylic acid can reduce recurrent viral infection in mice. These findings
      may implicate prostaglandins as agents in the viral reactivation process and
      suggest that therapy to suppress viral reactivation using nontoxic inhibitors of
      prostaglandin synthesis may be effective in humans.

PMID- 15512959
TI  - Mechanism of ganciclovir uptake by rabbit retina and human retinal pigmented
      epithelium cell line ARPE-19.
AB  - PURPOSE: The objective of this study was to elucidate the mechanism of
      ganciclovir uptake by the rabbit retina and the human retinal pigmented
      epithelium cell line ARPE-19. MATERIALS AND METHODS: [(3)H]Adenine,
      [(3)H]adenosine, [(3)H]thymidine, and [(3)H]ganciclovir were used to elucidate
      the mechanism of ganciclovir uptake by the ARPE-19 cell line and the isolated
      rabbit retinal tissue. Uptake studies using ARPE-19 cell line and isolated rabbit
      retina were carried out at 37 degrees C and 25 degrees C, respectively, for 5
      min. RESULTS: Uptake of [(3)H]adenine by ARPE-19 cells decreased by 95% in the
      presence of unlabeled adenine. Other nucleobases such as guanine, thymine, and
      uracil and the nucleosides adenosine, guanosine, thymidine, uridine, and inosine
      also reduced uptake of [(3)H]adenine by the ARPE-19 cells. Although
      [(3)H]adenosine and [(3)H]thymidine uptake was inhibited by nucleosides,
      nucleobases did not demonstrate any inhibitory effect, indicating that
      nucleosides can only bind to the nucleobase transporter but are not translocated
      by it. Uptake of the nucleosides and nucleobases by the ARPE-19 cells was sodium
      and pH independent. [(3)H]adenosine and [(3)H]thymidine uptake by the ARPE-19
      cells was inhibited by nanomolar quantities of nitrobenzylthioinosine. Uptake of
      [(3)H]adenine by the isolated rabbit retina was drastically reduced in the
      presence of unlabeled adenine. Unlabeled thymidine and guanosine, and removal of
      sodium from the uptake medium, inhibited uptake of [(3)H]thymidine by the rabbit
      retina. Nucleosides, nucleobases, and unlabeled ganciclovir did not exhibit any
      inhibitory effect on [(3)H]ganciclovir uptake by the isolated rabbit retina or
      ARPE-19 cells. CONCLUSIONS: Our results indicate that although the rabbit retina
      and the ARPE-19 cell line express nucleoside and nucleobase transporters,
      translocation of ganciclovir does not involve any carrier-mediated transport
      process. Rather, ganciclovir uptake by the rabbit retina and ARPE-19 cells is
      governed primarily by passive diffusion.

PMID- 15512960
TI  - Effect of acyclovir on thermal stress-induced herpesvirus reactivation.
AB  - PURPOSE: Acyclovir has been shown to be effective in preventing recurrent herpes
      simplex virus lesions of the genitalia and oral labia. The purpose of the current
      study was to determine the effect of acyclovir on the appearance of infectious
      virus in the peripheral nervous system and in an end organ, the eye. MATERIALS
      AND METHODS: Mice latent for the McKrae strain of herpes simplex virus type 1
      were given 3.5 mg/ml acyclovir in their drinking water. Control animals received
      water without drug. Acyclovir treatment was continued for 4 successive days. On
      the third day, the mice were subjected to a brief period of hyperthermic stress
      to induce viral reactivation. Twenty-four hours after stress induction, swabs of
      the ocular surface and homogenates of the cornea and trigeminal ganglia were
      analyzed for the presence of infectious herpes simplex virus type 1 and viral
      DNA. RESULTS: Acyclovir treatment significantly decreased the frequency of
      infectious virus in the ocular tear film and the cornea but not in the trigeminal
      ganglion. The corneal homogenates of acyclovir-treated animals contained smaller
      amounts of viral DNA compared with untreated controls, whereas the amounts of
      viral DNA in the trigeminal ganglia of acyclovir-treated and untreated animals
      were similar. CONCLUSIONS: These results suggest that oral administration of
      acyclovir, at least at the dose used in this study, is effective in modestly
      reducing viral replication in peripheral tissues such as the eye but is not
      effective in inhibiting viral reactivation and viral DNA synthesis in the
      peripheral nervous system in mice subjected to induction of reactivation by
      hyperthermic stress.

PMID- 15512961
TI  - Involvement of CD8+ T-cells in exacerbation of corneal scarring in mice.
AB  - PURPOSE: To determine the specific immune responses involved in the exacerbation
      of corneal scarring induced by HSV-1 in gK vaccinated mice. MATERIALS AND
      METHODS: BALB/c mice were vaccinated with HSV-1 glycoprotein K (gK) and ocularly
      challenged with HSV-1. Infiltration into the cornea of T cells and macrophages
      was monitored by immunocytochemistry, and the effect of depletion of CD4+ T
      cells, CD8+ T-cells, or macrophages on corneal scarring was determined. RESULTS:
      Following ocular challenge, CD4+ and CD8+ T-cells and macrophages were more
      abundant in the corneas of gK-vaccinated mice than in the corneas of mock
      vaccinated mice. Depletion of CD8+ T-cells, but not of CD4+ T-cells or
      macrophages, reduced the severity of corneal scarring in gK-vaccinated mice.
      CONCLUSIONS: We have shown that gK vaccination causes an overall increase in T
      cells and macrophages in the cornea after ocular HSV-1 challenge. The
      immunopathology induced by gK vaccination appears to be related to CD8+ T-cell
      activity, as depletion of these cells, but not other immune cells, reduced
      corneal scarring.

PMID- 15512962
TI  - Amino acid prodrugs of acyclovir as possible antiviral agents against ocular HSV
      1 infections: interactions with the neutral and cationic amino acid transporter
      on the corneal epithelium.
AB  - PURPOSE: The aim of this study was to explore the feasibility of improvement of
      ocular bioavailability of the antiviral agent acyclovir by designing amino acid
      prodrugs targeted to the amino acid transporters on the rabbit cornea. MATERIALS
      AND METHODS: Transcorneal flux of two water-soluble amino acid ester prodrugs of
      acyclovir (ACV), gamma-glutamate-ACV (EACV) and L-tyrosine-ACV (YACV), was
      studied across freshly excised rabbit cornea. Chemical and enzymatic hydrolysis
      studies of the two prodrugs were also conducted. RESULTS: EACV inhibited the
      uptake of [(3)H]L-Arg in rabbit primary corneal epithelial cells (rPCECs). The
      compound also exhibited longer half-life (t(1/2)) in cornea in comparison to
      YACV. Transcorneal flux of EACV was observed to be concentration-, energy-, and
      sodium-dependent and independent of pH within the range studied. EACV transport
      was inhibited by neutral and cationic amino acids, L-ornithine (specific for
      cationic amino acids), and BCH (2-aminobicyclo-[2,2,1]-heptane-2-carboxylic-acid)
      (specific inhibitor for L-type system and B(0,+) system). On the other hand, YACV
      was not recognized by this amino acid transporter as it failed to inhibit the
      uptake of [(3)H]Arg, and also its transport across cornea was not inhibited by
      arginine. YACV and EACV exhibited excellent antiviral activity against HSV-1 and
      2 and Varicella-Zoster Virus (VZV) in comparison to ACV. CONCLUSIONS: Analyses of
      the inhibition pattern of EACV transport suggests the involvement of a single
      transport system; namely, B(0,+). Design of amino acid prodrugs seems to be an
      attractive strategy to enhance the solubility of the otherwise poorly aqueous
      soluble compounds and also to afford a targeted and possibly enhanced delivery of
      the active drug.

PMID- 15512963
TI  - Evaluation of the antitumor effects of Herpes simplex virus lacking
      ribonucleotide reductase in a murine retinoblastoma model.
AB  - PURPOSE: To determine if an attenuated herpes simplex virus (HSV) lacking the
      large subunit of ribonucleotide reductase has antitumor effects in a transgenic
      mouse model of retinoblastoma (LHbetaTAg). METHODS: LHbetaTAg mice were injected
      ocularly with 1 x 10(6) pfu of the hrR3 virus and tumor sizes were measured 3
      weeks later. Replication of the virus in the eye and cultured murine
      retinoblastoma cells was tested by titration. Distribution of the virus in tumor
      was measured by X-gal staining. RESULTS: Intraocular injection of mice with hrR3
      (n = 24) did not result in a significant reduction in tumor size compared to
      uninjected (n = 24) or PBS injected controls (n = 16). Neither the hrR3, nor the
      HSV RE6 mutant, which was previously shown to have antitumor effects in vivo,
      replicated in cultured murine tumor cells in vitro, compared to wild-type HSV.
      The hrR3 virus also did not replicate significantly in tumor cells in vivo,
      compared to normal eye tissue. CONCLUSIONS: These results suggest that mutant HSV
      lacking ribonucleotide reductase do not display oncolytic activity in the
      LHbetaTAg mouse and that this model may not be suitable for studying viral
      oncolysis as a therapy for retinoblastoma.

PMID- 15512964
TI  - Susceptibility to murine cytomegalovirus retinitis during progression of MAIDS:
      correlation with intraocular levels of tumor necrosis factor-alpha and interferon
      gamma.
AB  - PURPOSE: To correlate tumor necrosis factor-alpha (TNF-alpha) and interferon
      gamma (IFN-gamma) synthesis with histopathologic disease and virus replication
      within murine cytomegalovirus (MCMV)-infected eyes during progression of murine
      acquired immunodeficiency syndrome (MAIDS). MATERIALS AND METHODS: Groups of
      normal mice and mice with MAIDS of 2-weeks (MAIDS-2), 4-weeks (MAIDS-4), and 12
      weeks (MAIDS-12) duration were infected uniocularly with MCMV by subretinal MCMV
      injection. MCMV-inoculated eyes from all mice were subjected to histopathologic
      analysis, quantitative plaque assay, or cytometric bead array analysis for
      quantification of TNF-alpha and IFN-gamma. RESULTS: Whereas MCMV-inoculated eyes
      of normal, MAIDS-2, and MAIDS-4 mice were resistant to MCMV retinitis, all MCMV
      inoculated eyes of MAIDS-12 mice developed retinitis. Surprisingly, MCMV
      inoculated eyes of MAIDS-4 mice without retinitis harbored high amounts of
      infectious virus at a level equivalent to that of MCMV-inoculated eyes of MAIDS
      12 mice that developed retinitis. Intraocular TNF-alpha levels were consistently
      approximately 50% greater in MCMV-inoculated eyes of MAIDS-12 mice when compared
      with TNF-alpha levels of normal, MAIDS-2, and MAIDS-4 mice. In contrast,
      intraocular INF-gamma levels within MCMV-inoculated eyes progressively declined
      as animals became susceptible to retinitis. CONCLUSIONS: An inverse relationship
      exists between TNF-alpha and INF-gamma production within MCMV-inoculated eyes
      during MAIDS evolution that is characterized by an increase in intraocular TNF
      alpha levels and a concomitant decrease in intraocular INF-gamma levels.
      Susceptibility of MCMV-inoculated eyes to virus replication and development of
      necrotizing retinitis are independent events with susceptibility to MCMV
      replication preceding susceptibility to MCMV retinitis by several weeks. Time of
      Th1/Th2 shift in cytokine profile appears to be a crucial event in the
      pathogenesis of MAIDS-related MCMV retinitis.

PMID- 15512965
TI  - Glycoprotein C of herpes simplex virus type 1 is required to cause keratitis at
      low infectious doses in intact rabbit corneas.
AB  - PURPOSE: To determine whether the herpes simplex virus type 1 (HSV-1) viral
      glycoprotein C (gC) plays a role in induction of keratitis in unscarified and
      scarified rabbit eyes. MATERIALS AND METHODS: A gC deletion mutant (DeltagC) was
      constructed and then rescued back to wild type (wt) for use as a control.
      Following ocular infection with each virus in rabbit eyes, with or without prior
      corneal scarification, keratitis was compared. RESULTS: At low infection doses of
      2 x 10(3) and 2 x 10(4) plaque-forming units (PFU)/eye, in unscarified cornea,
      DeltagC produced significantly less keratitis than did wt virus (p = 0.007 and
      0.03, respectively). In contrast, the keratitis induced by DeltagC was similar to
      that induced by the wt virus (p > 0.60) in scarified cornea. At high infection
      dose (2 x 10(5) PFU/eye), keratitis induced by DeltagC was similar in scarified
      and unscarified cornea, and the severity of disease was similar to that seen in
      scarified eyes at the low-dose DeltagC infections. Interestingly, although
      DeltagC induced keratitis with or without corneal scarification at high infection
      doses, the severity of disease was significantly less than that induced by wt
      infection. At all infection doses, keratitis induced by wt infection was similar
      in scarified and unscarified eyes. CONCLUSIONS: These results suggest that (1) at
      low infection doses, in unscarified corneas, gC is required for HSV-1 induced
      keratitis; (2) corneal scarification prior to infection can circumvent the need
      for gC at low doses, but (3) at higher doses, gC is required for wild-type levels
      of keratitis even in scarified cornea.

PMID- 15512966
TI  - Temporal expression of herpes simplex virus type 1 mRNA in murine retina.
AB  - PURPOSE: During maturation of herpes simplex virus type 1 (HSV) in infected
      murine retinal F strain ganglion cells, new viral components are axonally
      transported in two phases. The viral envelope protein (gD) appears 48 hr before
      the capsid protein (VP5). Our hypothesis was that delayed appearance of VP5 mRNA
      in the infected eye causes the delayed expression of the VP5 protein in the axon.
      METHODS: HSV was injected into the ocular posterior chamber. Three to 24 hr
      later, the mice were euthanized, and the posterior eye was isolated. RNA was
      extracted, DNAase-treated, and used for amplification by reverse transcription
      polymerase chain reaction (RT-PCR) using primers specific to gD, VP5 and a
      tegument protein VP22. RESULTS: VP22 and gD mRNAs are expressed 6 hr and VP5 mRNA
      is first detected 9 hr after infection. CONCLUSIONS: The results establish that
      delayed transcription does not play a significant role in the 48-hr delay in VP5
      appearance in the retinal axons.

PMID- 15512967
TI  - Feasibility of an antiviral clinical trial requiring cross-country shipment of
      conjunctival adenovirus cultures and recovery of infectious virus.
AB  - PURPOSE: Accurate and timely laboratory diagnosis of adenovirus from conjunctival
      cultures is essential to ensure appropriate enrollment, and detection of residual
      infectious virus is essential to evaluate antiviral efficacy in any multicenter
      national clinical trial. As part of a feasibility study, we investigated those
      variables that might affect the successful recovery of infectious adenovirus from
      patient conjunctival cultures after cross-country shipment. MATERIALS AND
      METHODS: Simulated adenovirus conjunctival cultures were prepared in viral
      transport media to evaluate the effect of four variables (adenovirus serotype,
      initial concentration, initial storage temperature [-20 degrees C, 0 degrees C,
      20 degrees C], and preshipment storage times [1-5 days]) on the recovery of
      infectious adenovirus by a central laboratory in St. Paul, MN, following air
      shipment from Pittsburgh, PA. Upon arrival, the internal temperatures of the
      containers were recorded, and the samples were cultured on A549 cells using
      standard tube and/or shell vial culture. RESULTS: Overall, adenovirus was
      recovered in 352/354 (99.4%) of the samples when the initial titer was greater
      than 1.0 PFU/ml. Adenovirus serotype, initial storage temperature, and
      preshipment storage times had no adverse effect on virus recovery. CONCLUSIONS:
      Simulated conjunctival samples could successfully be shipped cross-country at
      ambient temperatures to a commercial laboratory for adenovirus isolation by
      culture. Having demonstrated feasibility, a clinical trial was subsequently
      carried out that confirmed the ease of shipment and recovery of infectious
      adenovirus from conjunctival cultures.

PMID- 15512968
TI  - Herpesvirus infection of ICAM-1-deficient mice.
AB  - PURPOSE: To determine the effect of ICAM-1 deficiency on viral infection of the
      cornea. MATERIALS AND METHODS: Wild-type and intercellular adhesion molecule 1
      (ICAM-1)-deficient mice were infected with the RE strain of herpes simplex virus
      type 1 (HSV-1). Corneal swabs and trigeminal ganglia were obtained and analyzed
      for infectious virus. Corneas and trigeminal ganglia were evaluated for signs of
      inflammation by immunohistochemical staining and for interferon-gamma (IFN-gamma)
      producing cells by enzyme-linked immunospot assay (ELISPOT). Serum anti-HSV-1
      antibody titers were determined by enzyme-linked immunosorbent assay (ELISA).
      RESULTS: Viral titers in corneal swabs from the wild-type and ICAM-1-deficient
      mice were not significantly different during the 21-day study. Infectious virus
      was present in the trigeminal ganglia of wild-type and ICAM-1-deficient mice
      through day 6 after infection. Serum anti-HSV-1 antibody titers were
      significantly higher in wild-type mice 6 days after infection, compared with ICAM
      1-deficient mice; by day 8 and thereafter, however, antibody titers were not
      significantly different. Production of interferon gamma was greater in trigeminal
      ganglion cells from wild-type mice stimulated with interleukin 12 and interleukin
      18 on days 4, 6, and 8 after infection compared with cells from ICAM-1-deficient
      mice. Histopathologic analysis of corneal and ganglion sections from wild-type
      and ICAM-1-deficient mice showed no significant differences in the time-course of
      appearance or the intensity of the inflammatory infiltrate. Immunohistochemical
      staining for CD3(+) T-lymphocytes and CD11b(+) neutrophils and macrophages
      demonstrated equivalent numbers of these cells in the corneas and trigeminal
      ganglia of wild-type and ICAM-1-deficient mice. CONCLUSIONS: The results of these
      experiments indicate that ICAM-1 deficiency has only a modest effect on viral
      infection of the cornea and the development of an acquired immune response.

PMID- 15512969
TI  - Diagnosis of herpes simplex virus-1 keratitis: comparison of Giemsa stain,
      immunofluorescence assay and polymerase chain reaction.
AB  - PURPOSE: To evaluate three different diagnostic tests against the gold standard
      of viral isolation, in the diagnosis of HSV-1 keratitis. METHODS: Corneal
      scrapings from 170 patients with clinically suspected HSV keratitis were tested
      by; 1) Giemsa staining procedure for the presence of multinucleated giant cells
      and lymphocytes, 2) immunofluorescence assay for HSV-1 antigen, 3) polymerase
      chain reaction (PCR) for HSV-1 DNA and 4) virus isolation by shell vial culture
      in SIRC (Rabbit corneal epithelial cell line). The results of the former three
      tests were compared among 14 cases that were culture positive and 156 cases that
      were culture negative for HSV-1. RESULTS: The sensitivity of PCR was 100%, while
      IFA and Giemsa had sensitivities of 85.7% and 57.1% respectively. The specificity
      of PCR, IFA and Giemsa were found to be 67.9%, 85.3% and 85.9% respectively.
      CONCLUSIONS: In the present study, a combination of PCR and immunofluorescence
      assay appears to be the most suitable choice of tests for diagnosis of HSV-1
      keratitis, while detection of MNGC by Giemsa staining procedure may give us a
      presumptive diagnosis of suspected viral infection.

PMID- 15512970
TI  - Efficacy of antiviral agents in feline herpetic keratitis: results of an in vitro
      study.
AB  - PURPOSE: To determine, by a plaque reduction assay, the in vitro efficacy of
      novel antiviral agents in the treatment of feline herpes virus 1 (FHV-1)
      keratitis in the domestic cat (Felis felis). MATERIALS AND METHODS: A standard
      plaque reduction assay was performed using a laboratory strain of FHV-1 and
      embryo-derived feline kidney cells to determine the in vitro efficacy of the
      antiviral drugs penciclovir (PCV), bromovinyldeoxyuridine (BVdU), and (S)-9-(3
      hydroxy-2-phosphonylmethoxypropyl) adenine (HPMPA) and to compare these with the
      drugs acyclovir (ACV) and trifluorothymidine (TFT). Efficacy was assessed by
      determining the dose of drug at which 50% plaque reduction was noted (ED(50)).
      RESULTS: HPMPA was found to have greatest antiviral activity (ED(50) 0.07
      microg/ml). ACV was least active (ED(50) 24 microg/ml), while TFT was active with
      an ED(50) of 5.7 microg/ml. PCV and BVdU had intermediate activity (ED(50) 1.6
      and 1.7 microg/ml, respectively). CONCLUSIONS: This study suggests that the
      efficacy of HPMPA, BVdU, and penciclovir in cats with herpesviral keratitis
      should be determined in vivo as their efficacy in vitro was substantially greater
      than that of acyclovir, already shown to have demonstrable but limited clinical
      antiviral activity.

PMID- 15512971
TI  - What is the role of the precautionary principle in the philosophy of medicine and
      bioethics?

PMID- 15512972
TI  - Toward understanding aspects of the precautionary principle.
AB  - The idea of a precautionary principle (or precautionary principles) is beginning
      to come to the wider attention of the environmental community, governmental
      agencies, regulatory agencies, and the regulated community. Different
      precautionary principles have not been specified in detail, and, of course, this
      is difficult to do. Yet some specification must be done in order to understand it
      better and, if it is to be used for specific action-guidance, to implement it.
      Moreover, it is important to understand more about the principle, its background
      assumptions and its comparison with other principles to which we might subscribe.
      This paper explores aspects of the PP and its background assumptions and
      presuppositions, comparing them with those for risk assessment and other
      statements of the PP. It also briefly indicates how it resembles legal principles
      in addressing problems of uncertainty. Finally, it recapitulates two possible
      versions of the PP and suggests an application of it for an emerging threat to
      the environment and public health. This review suggests the PP has plausible
      applications and is not the radical principle some have suggested.

PMID- 15512973
TI  - The precautionary principle and medical decision making.
AB  - The precautionary principle is a useful strategy for decision-making when
      physicians and patients lack evidence relating to the potential outcomes
      associated with various choices. According to a version of the principle defended
      here, one should take reasonable measures to avoid threats that are serious and
      plausible. The reasonableness of a response to a threat depends on several
      factors, including benefit vs. harm, realism, proportionality, and consistency.
      Since a concept of reasonableness plays an essential role in applying the
      precautionary principle, this principle gives physicians and patients a decision
      making strategy that encourages the careful weighing and balancing of different
      values that one finds in humanistic approaches to clinical reasoning. Properly
      understood, the principle presents a worthwhile alternative to approaches to
      clinical reasoning that apply expected utility theory to decision problems.

PMID- 15512974
TI  - The precautionary principle: a dialectical reconsideration.
AB  - This essay examines an overlooked element of the precautionary principle: a
      prudent assessment of the long-range or remote catastrophes possibly associated
      with technological development must include the catastrophes that may take place
      because of the absence of such technologies. In short, this brief essay attempts
      to turn the precautionary principle on its head by arguing that, (1) if the long
      term survival of any life form is precarious, and if the survival of the current
      human population is particularly precarious, especially given contemporary urban
      population densities, and (2) if technological innovation and progress are
      necessary in order rapidly to adapt humans to meet environmental threats that
      would otherwise be catastrophic on a large scale (e.g., pandemics of highly
      lethal diseases), then (3) the development of biomedical technologies in many
      forms, but in particular including human germ-line genetic engineering, may be
      required by the precautionary principle, given the prospect of the obliteration
      of humans in the absence of such enhanced biotechnology. The precautionary
      principle thus properly understood requires an ethos that should generally
      support technological innovation, at least in particular areas of biotechnology.

PMID- 15512975
TI  - Precaution, prevention, and public health ethics.
AB  - The precautionary principle brings a special challenge to the practice of
      evidence-based public health decision-making, suggesting changes in the
      interpretative methods of public health used to identify causes of disease. In
      this paper, precautionary changes to these methods are examined: including
      discounting contrary evidence, reducing the number of causal criteria, weakening
      the rules of evidence assigned to the criteria, and altering thresholds for
      statistical significance. All such changes reflect the precautionary goal of
      earlier primary preventive intervention, i.e. acting on insufficient evidence,
      the least amount, or minimum level, of evidence for causation. Evaluating the
      impact of these changes will be difficult without a careful study of how well the
      current methods of causal inference work, their theoretical foundations, and the
      ethical implications of their applications. That research program will be most
      productive if it is jointly developed by public health professionals trained in
      the ethics and philosophy and by bioethicists and philosophers trained in the
      theories, methods, and practice of public health.

PMID- 15512976
TI  - The precautionary principle and the regulation of U.S. food and drug safety.
AB  - This article probes the advisability of regulating U.S. food and drug safety
      according to the precautionary principle. To do so, a precautionary regulatory
      regime is formulated on the basis of the beliefs that motivate most proponents of
      this initiative. That hypothetical regime is critically analyzed on the basis of
      an actual instantiation of a similarly stylized initiative. It will be argued
      that the precautionary principle entails regulatory constraints that are apt to
      violate basis tenets of political legitimacy. The modifications that would change
      this finding would also change precautionary regulation to the point that it
      would be indistinguishable from orthodox safety protocols. It is concluded on the
      basis of its impoverished content that the precautionary principle should not be
      taken seriously as a formal approach to the regulation of U.S. food and drug
      safety.

PMID- 15512977
TI  - Minimal risk as an international ethical standard in research.
AB  - Classifying research proposals by risk of harm is fundamental to the approval
      process and the most pivotal risk category in most regulations is that of
      "minimal risk." If studies have no more than a minimal risk, for example, a
      nearly worldwide consensus exists that review boards may sometimes: (1) expedite
      review, (2) waive or modify some or all elements of informed consent, or (3)
      enroll vulnerable subjects including healthy children, incapacitated persons and
      prisoners even if studies do not hold out direct benefits to them. The moral and
      social purposes behind this threshold are discussed along with relevant views
      from the National Commission, NBAC, NHRPAC, Grimes v. Kennedy Krieger Institute,
      The Nuremberg Code, and The WMA's Declaration of Helsinki. Representative
      policies from Australia, Canada, South Africa, the U.S., and CIOMS are reviewed
      revealing different understandings of this sorting threshold. Six of nine
      frequently cited interpretations of "minimal risk" are untenable. The "absolute"
      interpretation of the "routine examination" standard is defended as best.

PMID- 15512978
TI  - Sarcoidosis and scleritis.

PMID- 15512979
TI  - Clinical mini-review: systemic lupus erythematosus and the eye.
AB  - Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease, the
      exact etiology of which is unknown. It is characterized by the production of
      pathological autoantibodies which adhere to cellular surfaces or form immune
      complexes which deposit in tissue, leading to end-organ damage via inflammatory
      mechanisms including complement activation. SLE may manifest itself in any organ
      system. In the eye, keratoconjunctivitis sicca is the most common finding. Other
      ophthalmic sites of involvement include the cornea, conjunctiva, episclera,
      sclera, uveal tract, retina, vasculature, optic nerve, and orbit. Therapy varies
      based on the disease manifestation and severity.

PMID- 15512980
TI  - Antigen-presenting cells are targets of regulatory T cells similar to those that
      mediate anterior chamber-associated immune deviation.
AB  - PURPOSE: To identify the means by which in-vitro-generated regulatory T cells,
      similar to those in anterior chamber-associated immune deviation (ACAID),
      suppress antigen-specific T-cell responses. METHODS: T regulators (T regs),
      generated by stimulating ovalbumin (OVA)-specific Tcr transgenic DO11.10 T cells
      with OVA-pulsed, TGF-beta2-treated peritoneal exudates cells (PEC), or their
      supernatants were added to OVA-pulsed PEC that were used to activate DO11.10 T
      cells in vitro or to suppress OVA-specific delayed hypersensitivity (DH)
      induction in vivo. RESULTS: OVA-pulsed PECs exposed in vitro to TGF-beta
      producing T regs or their supernatants failed to activate DO11.10 T cells in
      vitro, and suppressed DH in mice immunized with OVA plus adjuvant. CONCLUSION: T
      cells exposed to TGF-beta2-pretreated, antigen-pulsed PECs secrete soluble
      factors, including active TGF-beta that regulate OVA-specific responses by
      forcing antigen-presenting cells to promote deviant T-cell activation in vitro
      and in vivo.

PMID- 15512981
TI  - Blocking CD200-CD200 receptor axis augments NOS-2 expression and aggravates
      experimental autoimmune uveoretinitis in Lewis rats.
AB  - PURPOSE: Tissue expression of CD200 generates inhibitory or down-regulatory
      signals to macrophages and microglia within CNS and retina. Our interests were to
      investigate whether blocking CD200 receptor (CD200R) signalling in vivo results
      in macrophage activation and thus aggravation of EAU in Lewis rats. METHODS:
      Retinal extract-immunised Lewis rats were treated day 3 and 5 post-immunisation
      with CD200R mAb or normal mouse serum. Phenotypic analysis of the leucocyte
      infiltrate and disease severity was clinically and histogically examined.
      RESULTS: Rats administered with CD200R mAb developed earlier onset of EAU and
      more severe disease. Blocking CD200R increased retinal neuronal CD200 expression
      and, although disease severity was increased concomitant with an increase in NOS
      2 expression, retinal macrophage numbers were not increased. CONCLUSIONS:
      Contemporaneous with data from CD200KO mice, these results support the notion
      that CD200-CD200R signalling suppresses macrophage activation. Exacerbation of
      EAU in both CD200KO mice and Lewis rats when CD200-CD200R interaction is blocked
      suggests that this could be an avenue for therapeutic intervention.

PMID- 15512982
TI  - Nm23 expression in retinoblastoma.
AB  - PURPOSE: Nm23 is a metastasis-suppressor protein. Decreased nm23 protein
      contributes to aggressiveness in many tumors. Nm23 immunoreactivity was studied
      in retinoblastoma and correlated with differentiation and invasiveness. METHODS:
      Immunohistochemistry was performed on 73 formalin-fixed, paraffin-embedded
      specimens of retinoblastoma. Western blot was conducted to confirm the
      immunohistochemical study. Prognostic features such as differentiation, invasion
      of choroid, optic nerve, and orbit, and metastasis were analyzed. RESULTS:
      Intense nm23 immunoreactivity was seen in 61% of the retinoblastomas with no
      invasion and faint nm23 immunoreactivity was seen in 85% of the retinoblastomas
      with invasion (p < 0.001). Poorly differentiated retinoblastoma showed decreased
      nm23 immunoreactivity compared to well-differentiated retinoblastomas (p = 0.02).
      An inverse correlation was observed between invasion of choroid, optic nerve,
      orbit, and metastasis, and nm23 immunoreactivity. Western blot assays of fresh
      tumor extracts confirmed the immunohistochemical findings. CONCLUSIONS: Decreased
      nm23 immunoreactivity was seen in poorly differentiated retinoblastomas and in
      retinoblastomas with invasiveness. These findings may lay the groundwork for
      further studies to better understand the molecular mechanisms and provide a more
      accurate prediction of invasion and metastasis of retinoblastoma.

PMID- 15512983
TI  - Multiple sclerosis-associated uveitis.
AB  - BACKGROUND/AIMS: To describe the clinical characteristics and course of 16
      patients with uveitis associated with multiple sclerosis (MS). METHODS: The
      records of 1254 patients with uveitis were reviewed. Sixteen of these patients
      had MS. The history, review of systems, ocular findings, and clinical test
      results of each of these 16 subjects were analyzed. The mean follow-up time was
      38 months. RESULTS: Most patients with MS-associated uveitis were white females
      between 20 and 50 years of age. The diagnosis of MS preceded the onset of uveitis
      in 56%, followed it in 25%, and was made concurrently in 19% of the cases. In
      94%, the uveitis was bilateral. Pars planitis was the most frequent form of
      uveitis in our study population (81%); concomitant anterior chamber inflammation
      was common and was granulomatous in nature 56% of the time. Forty-one percent of
      the eyes with MS-associated uveitis had 20/30 or better initial visual acuity.
      Among these treated patients, significant loss of visual acuity was uncommon.
      CONCLUSIONS: MS-associated uveitis should be suspected in white female patients
      with bilateral uveitis, especially if pars planitis is present. These patients
      often retain useful vision for many years if treated.

PMID- 15512984
TI  - Scleritis associated with sarcoidosis.
AB  - PURPOSE: To review scleritis cases associated with sarcoidosis and to evaluate
      clinical features, medical treatment, and clinical course. METHODS: Two cases of
      diffuse anterior scleritis and a nodular scleritis case associated with systemic
      sarcoidosis were evaluated. Scleritis was the first manifestation of sarcoidosis
      in two of the patients and the diagnosis of sarcoidosis was confirmed with a
      conjunctival biopsy. The third patient had the diagnosis of systemic sarcoidosis
      when she developed scleritis. RESULTS: Based on the clinical and histological
      appearance, two patients presented with bilateral diffuse anterior scleritis and
      the third patient with an anterior nodular scleritis. One patient already had the
      diagnosis of systemic sarcoidosis at presentation, while ocular findings led to
      the diagnosis in the other two cases. Conjunctiva or skin biopsies revealed
      features compatible with the diagnosis of sarcoidosis. Scleritis attacks recurred
      in two patients. All patients responded well to systemic corticosteroid
      (prednisone) therapy. CONCLUSIONS: Scleritis associated with sarcoidosis has
      rarely been described and it may be the presenting sign of systemic sarcoidosis.

PMID- 15512985
TI  - Posterior scleritis in Cogan's syndrome.
AB  - PURPOSE: To describe an unusual case of atypical Cogan's syndrome with features
      of posterior scleritis. METHODS: Interventional case report. RESULTS: A 53-year
      old man presented with bilateral posterior scleritis, along with sensorineural
      hearing loss and systemic vasculitis. Systemic corticosteroid therapy was started
      with resolution of ophthalmic findings and improvement of vestibuloauditory
      symptoms. CONCLUSIONS: In the setting of atypical Cogan's syndrome, ophthalmic
      manifestations may be the first sign of disease.

PMID- 15512986
TI  - Panuveitis associated with multiple sclerosis complicated by cerebral venous
      thrombosis.
AB  - PURPOSE: To report cerebral venous thrombosis as a complication of intravenous
      corticosteroid treatment in a patient with multiple sclerosis. METHOD: A case
      report. A 44-year-old woman with a previous diagnosis of multiple sclerosis
      presented with panuveitis and retinal perivasculitis. Intravenous pulse
      corticosteroid therapy was given for three days. RESULTS: The panuveitis and
      retinal periphlebitis began to resolve within one week; however, ten days after
      the last corticosteroid dose, the patient was hospitalized with the diagnosis of
      cerebral venous thrombosis. CONCLUSION: Although intravenous corticosteroid
      treatment for uveitis associated with multiple sclerosis can be very helpful, the
      patient should be monitored closely for systemic side effects.

PMID- 15512987
TI  - Journal watch.

PMID- 15512988
TI  - Quality of life in glaucoma patients: regression analysis and correlation with
      possible modifiers.
AB  - PURPOSE: To verify the quality of life in a Brazilian glaucoma population and the
      influence of possible modifiers (e.g., visual acuity, visual field impairment).
      METHODS: Forty-five consecutive patients from CEROF - Federal University of
      Goias, Brazil were included prospectively in the study. The quality of life was
      assessed using the Portuguese version of the VFQ. Possible modifiers were
      evaluated, initially separately with the Spearman's Correlation and then together
      in a regression model. RESULTS: The mean age was 59.6 +/- 12.4 years. The mean
      quality of life score was 79 +/- 15 (range 45-100). Age (r = -0.402, p = 0.006),
      visual acuity in the better eye (r = -0.497, p = 0.001) and in the worse eye (r =
      -0.608, p < 0.001), Hodapp-Parrish-Anderson visual field grading scale in the
      better (r = -0.353, p = 0.01) and worse eye (r = -0.387, p = 0.009), visual field
      Mean Deviation (MD) in the better (r = 0.355, p = 0.01) and worse eye (r = 0.320,
      p = 0.04) and ability to perform a visual field test in both eyes (r = -0.397, p
      = 0.007) were significantly correlated with the quality of life scores. However,
      only age (younger, better quality of life, p = 0.008) and visual acuity in the
      better eye (direct relation, p = 0.04) were significant in the regression model
      (r = 0.633, r(2) = 0.401). CONCLUSIONS: The VFQ may be a useful tool to assess
      the quality of life in glaucoma patients. The preliminary results indicate that
      age and visual acuity in the better eye are the main factors related to the
      quality of life in these patients.

PMID- 15512989
TI  - Five-year incidence of cataract in older persons with diabetes and pre-diabetes.
AB  - PURPOSE: To investigate longitudinal associations between diabetes and the 5-year
      incidence of cataract and cataract surgery. (A population-based, cohort study of
      2335 persons with baseline ages 49 years or older resident in the Blue Mountains
      region, west of Sydney, Australia). METHODS: Baseline information on diabetes
      history was collected during an interviewer-administered questionnaire. Impaired
      Fasting Glucose (IFG) was defined as venous plasma glucose between 6.0 and 7.0
      mmol/L and newly diagnosed diabetes as plasma glucose >7.0 mmol/L, using fasting
      blood glucose measurements taken at baseline. Retroillumination lens photographs
      from the baseline and 5-year follow-up examinations were graded for presence of
      cortical, posterior subcapsular (PSC) and nuclear cataract. RESULTS: We found a 2
      fold higher 5-year incidence of cortical cataract in participants with IFG,
      multivariate adjusted odds ratio (OR) 2.2, 95% confidence interval (CI) 1.1-4.1.
      Incident PSC cataract was more frequent among persons with diabetes, but this
      association was statistically significant only for those with newly diagnosed
      diabetes, multivariate adjusted OR 4.5 (CI 1.5-13.0). There were no statistically
      significant associations found between incident nuclear cataract or cataract
      surgery and either diabetes or IFG. CONCLUSIONS: These epidemiological data
      suggest that IFG, a pre-diabetic condition, may be a risk factor for the
      development of cortical cataract.

PMID- 15512990
TI  - Economic antecedents of temporal variation in the incidence of ocular trauma.
AB  - PURPOSE: To test the reciprocal risk hypothesis that the monthly number of
      unemployed persons in Alabama predicts: 1) the odds that a worker will suffer an
      ocular injury; and 2) the incidence of ocular injuries at home. METHODS: Data
      from the United States Eye Injury Registry and from the Bureau of Labor
      Statistics are analyzed with time series methods to test the hypotheses. RESULTS:
      As implied by the reciprocal risk hypothesis, the monthly odds of a worker
      reporting a job-related ocular injury decrease as the number of unemployed
      persons increases. The incidence of ocular injuries in the home, however,
      increases when the number of unemployed persons increases. CONCLUSIONS:
      Consistent with theory and earlier research, the incidence of ocular injuries
      appears related to the performance of the economy. Unlike earlier research,
      however, we find a reciprocal risk between injuries at work and home. The
      findings suggest that public health efforts to prevent injuries could be made
      more effective by strategically shifting the focus from home to work and vice
      versa depending on changes in the local economy.

PMID- 15512991
TI  - Coverage of cataract surgery per person and per eye: review of a community-based
      blindness survey in Oman.
AB  - BACKGROUND AND OBJECTIVE: The data from a national survey of blindness and common
      eye diseases in Oman in 1996 were reviewed. The objective was to compare the
      calculation of cataract surgery services coverage on a per eye and per person
      basis. The advantages and limitations of both methods of program management are
      evaluated. METHODS AND MATERIALS: The information on cataract status, visual
      status and past history/evidence of cataract surgery was collected for 11,415
      Omani subjects. The coverage of existing cataract services was calculated per eye
      and per person. The rates by gender, age groups, regional groups and type of
      cataract were also compared. RESULTS: The cataract surgery services could address
      more than 60% of the reported persons with blinding cataract (vision less than
      3/60) and more than half of the eyes with blinding cataract. The services could
      cover more than one-fourth of the persons with cataract (with any grade of vision
      defect) and less than one-fourth of the eyes with cataract. If the coverage of
      cataract services for blinding cataract is calculated using persons as the
      denominator, it is nearly 10% higher than that calculated using eyes as the
      denominator. CONCLUSIONS: The two methods of calculating the coverage of cataract
      services give different results and both are useful for monitoring ophthalmic
      services. A national program should implement a system for reporting the visual
      and cataract status of the fellow eye so that coverage rates could be calculated
      by person and by eye and the impact of the cataract services in relation to time,
      place, gender and resources could be reviewed.

PMID- 15512992
TI  - Socioeconomic conditions as determining factors in the prevalence of systemic and
      ocular toxoplasmosis in Northeastern Brazil.
AB  - OBJECTIVE: To determine the prevalence of systemic and ocular toxoplasmosis among
      1024 students in the city of Natal, Northeastern Brazil, and correlate it with
      demographic, socioeconomic and epidemiological risk factors. METHODS: The study
      population was randomly selected, asked to fill out a questionnaire, provide a
      blood sample for IgG and IgM (MEIA) serology and a hemogram, and undergo an eye
      examination. RESULTS: The seroprevalence for IgG was 46% (95% CI = 42.9-49.2%)
      and that for IgM was 1.4% (95% CI = 0.8-2.4%). The prevalence of ocular lesions
      was 1.15% (95% CI = 0.6-2.0%). In the univariate analyses, confirmed by
      multivariate analysis, the socioeconomic conditions were determinants in the
      prevalence of systemic and ocular toxoplasmosis (mother's schooling = literacy/OR
      = 2.9 and p < 0.001). CONCLUSIONS: The prevalence of systemic toxoplasmosis,
      although high, was lower than that found in studies performed in the South and
      Southeast of Brazil, and the incidence of ocular lesions was totally different,
      being lower by a factor varying from 5 to 17. Although important epidemiological
      variables, such as owning a cat, drinking unfiltered water or having had contact
      with lakes or rivers, were found to be correlated with toxoplasmosis in the
      preliminary analysis, they lost their influence when included in the logistic
      model. However, further studies must be undertaken to identify the reasons for
      these findings, including the determination of the strains of Toxoplasma gondii
      encountered in different regions of the country and the sources of the water
      utilized by these populations.

PMID- 15512993
TI  - Comparison of Nd : YAG capsulotomy rates following phacoemulsification with
      implantation of PMMA, silicone, or acrylic intra-ocular lenses in four European
      countries.
AB  - PURPOSE: The aim of this study was to compare the incidence of Nd : YAG laser
      capsulotomy after cataract surgery according to the type of intra-ocular lens
      material (PMMA, silicone, hydrophilic acrylic, hydrophobic acrylic) implanted in
      four European countries (France, Italy, Germany, Spain). DESIGN: A retrospective
      record review. PARTICIPANTS: A review of 1525 patients (first operated eye), aged
      50 to 80 years, operated on for cataract in 1996 or 1997 in 16 surgical centers
      (4 per country). METHODS: The study employed a retrospective cohort design.
      Charts were reviewed to collect information during at least a three-year period
      following cataract surgery to identify patients who underwent Nd : YAG laser
      capsulotomy postoperatively. MAIN OUTCOME MEASURES: Data on the type of intra
      ocular lens implanted was extracted from the patient notes, as was the date and
      outcome of the Nd : YAG laser intervention. Kaplan-Meier survival curve analysis
      with the time to Nd : YAG laser was performed on the data. RESULTS A total of
      1525 patients (first operated eye) were available for the study (n = 294 for
      hydrophilic acrylic, n = 384 for PMMA, n = 421 for hydrophobic acrylic, n = 426
      for silicone). There was a highly statistically significant difference between
      the IOL groups for the incidence of posterior capsule opacification (p < 0.001)
      and for Nd : YAG laser treatment (p < 0.001). The mean delay of Nd : YAG laser
      treatment from the date of cataract operation was 2.48 years (+/-1.70, ranging
      from 0 to 5.88 years). The rate of Nd : YAG laser capsulotomy over the follow-up
      period was lowest in the hydrophobic acrylic group (7.1%), followed by silicone
      (16.2%), PMMA (19.3%) and hydrophilic acrylic (31.1%), respectively. CONCLUSIONS:
      A low incidence of posterior capsular opacification (PCO) and Nd : YAG laser
      treatment was detected in hydrophobic acrylic IOLs in comparison to three other
      types of IOLs implanted in a large cohort of persons with age-related cataract.
      Choice of IOL type may reduce the need for Nd : YAG laser treatment, although
      further research on the reasons for this is needed.

PMID- 15512994
TI  - Color vision testing.
AB  - The science of color vision testing has evolved since its inception in the late
      1700s. Since then, the rudimentary technique of comparing color names has been
      replaced by more sophisticated methods. Commonly used tests in clinical practice
      today include isochromatic plates, arrangement tests, anomaloscopes, and lantern
      tests. Each category has unique attributes that make it suitable for a particular
      clinical situation. The clinician should be aware of the requirements for
      administering and grading each test type. Factors such as the quality of the
      illuminant and the size of the field of view are important elements in setting up
      a proper color vision laboratory. Currently, no treatment exists for congenital
      color vision defects. However, studies show that diagnosis of these defects early
      in life may help children adjust better to tasks at school and may help adults
      understand their limitations at work. Acquired color vision defects are often
      used as markers of ocular pathology in the clinical setting. Different color
      vision tests are appropriate for diagnosing the different categories of defects.
      Sometimes, a battery of tests may be appropriate. This paper is a review of the
      current knowledge in the field of color vision testing.

PMID- 15512995
TI  - Are Duane syndrome and infantile esotropia allelic?
AB  - PURPOSE: To evaluate the clinical overlap of families with Duane syndrome and
      infantile esotropia to determine whether the identification of genes for Duane
      syndrome may explain some cases of infantile esotropia. METHODS: Three separate
      groups of patients were evaluated. 1) Families with features of infantile
      esotropia were identified through the Strabismus Inheritance Study Tasmania
      (SIST). Clinical details of participants and their families were reviewed for any
      cases of Duane syndrome. 2) Cases of Duane syndrome were identified through the
      clinical diagnostic database at the Royal Children's Hospital, Melbourne, and
      private ophthalmology clinics in Melbourne and Tasmania. Previous medical notes
      were reviewed and family history of strabismus noted. All affected individuals
      were invited for re-examination in cases where a positive family history of
      strabismus was reported; siblings, parents, and other family members, where
      appropriate, were invited to be examined for signs of Duane syndrome or infantile
      esotropia. 3) Cases of mosaic trisomy 8, which has been associated with Duane
      syndrome and infantile esotropia, were reviewed for signs of strabismus. RESULTS:
      A total of 133 families from the SIST were reviewed, but no 'pure' families of
      Duane syndrome were identified. Two families with infantile esotropia had several
      members affected with Duane syndrome. Of the 40 index cases with Duane syndrome
      whose families agreed to be involved in the study, 21 had a family history of
      ocular motility disorders, but only two of these families had multiple cases of
      Duane syndrome. From 24 cases with mosaic trisomy 8, one individual case had
      Duane syndrome and another had mild congenital cataracts and infantile esotropia.
      CONCLUSIONS: There is clinical overlap in families with Duane syndrome and
      infantile esotropia. We confirmed the previous association of mosaic trisomy 8
      with both Duane syndrome and infantile esotropia. These data suggest that the two
      conditions may be allelic and may be due to a gene on chromosome 8.

PMID- 15512996
TI  - Ontogenetic development of visual acuity over the first three postnatal years.

PMID- 15512997
TI  - A missense mutation in GUCY2D acts as a genetic modifier in RPE65-related Leber
      Congenital Amaurosis.
AB  - Leber congenital amaurosis (LCA) is a clinically and genetically heterogeneous
      severe retinal dystrophy presenting in infancy. To explain the phenotypical
      variability observed in two affected siblings of a consanguineous pedigree
      diagnosed with LCA and establish a genotype-phenotype correlation, we screened
      GUCY2D, RPE65, CRX, AIPL1, and RPGRIP1 for mutations. The more severely affected
      sibling carried a heterozygous missense mutation in the GUCY2D gene (Ile539Val),
      which did not segregate with the disease phenotype. Subsequently, a homozygous
      nonsense mutation (Glu102STOP) in the RPE65 gene was identified in both affected
      siblings, thus identifying the causative gene. This data provides evidence for
      the presence of genetic modulation in LCA. It appears that the heterozygous
      GUCY2D mutation further disrupts the already compromised photoreceptor function
      resulting in more severe retinal dysfunction in the older sibling. We suggest
      that the unusual phenotypic variability in these two siblings with LCA is caused
      by the modifying effect of a heterozygous GUCY2D mutation observed against the
      disease background of a homozygous RPE65 mutation.

PMID- 15512998
TI  - Association of EFEMP1 with malattia leventinese and age-related macular
      degeneration: a mini-review.
AB  - Malattia leventinese (ML) or Doyne honeycomb retinal dystrophy (DHRD) was the
      first clinically and histopathologically described Mendelian maculopathy. The
      gene responsible for ML/DHRD, EFEMPI (fibulin-3/SI-5/FBNL) encodes a member of
      the fibulin family, a newly recognized family of extracellular matrix proteins.
      EFEMPImutations have not been found in age-related macular degeneration (AMD)
      patients despite the close phenotypic similarities between ML/DHRD and AMD. This
      non-correlating genotype/phenotype relationship between inherited and age-related
      conditions is typical for common age-related diseases. Biochemical pathways
      delineated in other diseases indicate that the gene associated with the inherited
      condition is nonetheless critical in age-related forms. This review summarizes
      current knowledge relating to ML/DHRD and EFEMPI,with discussion of why EFEMPI
      mutations are absent in AMD and how EFEMPI may be involved in the pathogenesis of
      ML/DHRD and AMD.

PMID- 15512999
TI  - Oculodentodigital dysplasia: study of ophthalmological and clinical
      manifestations in three boys with probably autosomal recessive inheritance.
AB  - Oculodentodigital dysplasia (ODDD) is a rare inherited disorder affecting the
      development of the face, eyes, teeth, and limbs. The majority of cases of ODDD
      are inherited as an autosomal dominant condition. There are few reports of
      probable autosomal recessive transmission. Affected patients exhibit a
      distinctive physiognomy with a narrow nose, hypoplastic alae nasi, and anteverted
      nostrils, bilateral microphthalmos, and microcornea. Sometimes iris anomalies and
      secondary glaucoma are present. There are malformations of the distal extremities
      such as syndactyly. In addition, there are defects in the dental enamel with
      hypoplasia and yellow discoloration of the teeth. Less common features include
      hypotrichosis, intracranial calcifications, and conductive deafness secondary to
      recurrent otitis media. We describe three brothers with ODDD. Their parents are
      first cousins and present no features of ODDD. These data are in favor of
      autosomal recessive inheritance and suggest genetic heterogeneity for this
      entity.

PMID- 15513001
TI  - Anterior ischemic optic neuropathy following off-pump cardiac bypass surgery.
AB  - Anterior ischemic optic neuropathy (AION) is a well-described cause of visual
      loss in patients who have undergone cardiac surgery with cardiopulmonary bypass.
      The etiology of AION following cardiac surgery with cardiopulmonary bypass is
      believed to be multifactorial. Microembolisation and pump-related platelet
      dysfunction have been considered risk factors for the development of AION
      following cardiac surgery with cardiopulmonary bypass. Currently, 10-15% of
      cardiac procedures are performed without cardiopulmonary bypass to reduce
      morbidity. To the best of our knowledge, this is the second report of a patient
      who underwent off-pump cardiac surgery and developed an AION postoperatively. The
      patient's potential risk factors were severe anemia, new onset of atrial
      fibrillation with rapid ventricular rate, hypotension postoperatively, a small
      optic disc, uncontrolled diabetes mellitus and a past medical history of
      hypertension and coronary artery disease.

PMID- 15513002
TI  - Amiodarone optic neuropathy--review.
AB  - The antiarrhythmic agent, amiodarone (Cordone), Pacerone), has been reported to
      cause optic neuropathy. However, the clinical manifestations are similar to non
      arteritic anterior ischemic optic neuropathy (AION), which makes diagnosing
      amiodarone optic neuropathy difficult. There is controversy whether or not
      amiodarone optic neuropathy actually exists as a distinct entity. The clinical
      manifestations and the proposed pathophysiology of amiodarone optic neuropathy
      are discussed.

PMID- 15513003
TI  - Optic neuritis in adults and children.
AB  - Most ophthalmologists will encounter optic neuritis in the course of their
      practice. The disease behaves very differently in children versus adults. The
      ONTT and CHAMPS trials have given us important data regarding prognosis and
      management in adults, including probability of developing MS. Optic neuritis in
      children, while less common, must be considered in the differential diagnosis of
      subacute visual loss, especially in children with bilateral impairment. Secondary
      causes of optic neuritis are more common in children and an investigation should
      be performed to assess for associated disease states. In both populations, the
      ophthalmologist will play a central role in the diagnosis, treatment, and
      management of these patients, whether it is an isolated case of optic neuritis or
      the initial presentation of a long-term struggle with MS. With the advent of
      immunomodulating therapy to minimize both the subsequent incidence and severity
      of MS, early diagnosis and appropriate management by the ophthalmologist has
      become even more critical.

PMID- 15513004
TI  - Recent developments in idiopathic intracranial hypertension (IIH).
AB  - Idiopathic intracranial hypertension is a disease with a predilection for young
      obese women. The most common symptoms are headache, transient visual obscuration
      and pulsatile tinnitus. The only focal neurologic finding is false-localizing 6th
      cranial nerve palsy. Papilledema is usually present and this can lead to optic
      atrophy with progressive permanent visual loss. The earliest visual loss is
      constriction of peripheral visual field, usually starting with the inferior nasal
      quadrant. Numerous theories have been entertained as to the pathogenesis but this
      still remains an open controversy. The most prevalent current theories involve
      increased resistance to cerebrospinal fluid reabsorption at the arachnoid
      granulations, either from intrinsic disease in the granulations or secondary to
      elevated pressure in the dural venous sinuses into which the cerebrospinal fluid
      is absorbed across the granulations. The syndrome of idiopathic intracranial
      hypertension was long ago recognized as a complication of recurrent otitis media
      with resultant thrombosis of the transverse and sigmoid dural venous sinuses.
      Cases secondary to dural venous sinus thrombosis are seldom encountered today
      because the incidence of chronic otitis is much less than in the past. The
      prevalent concept has been that the idiopathic cases in obese young women were
      not associated with pathology in the dural venous sinuses. A recent study using
      ATECO MR venography, which the authors claim to be more reliable than even
      conventional catheter venography, has demonstrated stenosis of the transverse and
      sigmoid dural venous sinuses distinguishes cases of idiopathic intracranial
      hypertension from controls with a high degree of sensitivity and specificity. The
      authors believe the stenosis is secondary to intracranial hypertension but that
      it may further aggravate the hypertension when it occurs.

PMID- 15513005
TI  - The evaluation of eye pain with a normal ocular exam.
AB  - Eye pain with or without associated head or face pain is a common complaint to
      the ophthalmologist. The ocular exam may reveal the etiology (e.g., corneal
      disease, angle closure glaucoma) but typically the exam is normal. This paper
      reviews the evaluation and management of eye pain with a "normal" ocular exam,
      including: 1) subtle findings on ocular exam; 2) transient findings on exam, and
      3) no abnormal ocular findings. Ophthalmologists should be aware of the various
      etiologies for eye pain and the specific and distinctive features that make the
      diagnosis.

PMID- 15513006
TI  - Treatment of headache with botulinum toxin administration.
AB  - Botulinum toxin has been increasingly applied to the treatment of a wide variety
      of neurological disorders. Its application to headache disorders, and
      specifically those classified as migraine or tension-type, followed the
      observation of its effectiveness in decreasing pain. Studies that have primarily
      used botulinum toxin type A, but with varying dose regimens and sites of
      administration, have since observed its beneficial effects and in those subjects,
      headaches have lessened in their frequency or severity. However, questions that
      have primarily concerned dose and sites of administration have since arisen and
      clear guidelines for botulinum toxin use in headache disorders have yet to be
      developed.

PMID- 15513007
TI  - Bilateral occipital-parietal hemorrhagic infarctions following chiropractic
      cervical manipulation.
AB  - A 26-year-old woman presented with acute headache and hand-motion vision in both
      eyes. One day prior to presentation she went to her chiropractor for cervical
      manipulation. The patient had received 20 chiropractic manipulations over the
      previous two years. CT scan and MRI showed bilateral, symmetric occipital
      parietal hemorrhagic infarctions. Angiography revealed severe focal stenosis in
      the distal vertebral arteries bilaterally at the superior C1 level possibly
      representing dissections. There was also a pseudoaneurysm of the left vertebral
      artery at the C1 level. Risk factors included chiropractic manipulation, recent
      fever, and therapies for polycystic ovarian disease. The patient showed slow,
      steady improvement in her vision. Twenty days following admission, vision was
      20/20 OU. The improvement in her vision most likely reflects the reduction in
      swelling and absorption of blood at the site of the strokes.

PMID- 15513008
TI  - Migraine with and without headache.
AB  - Transient visual and neurological episodes are relatively common and can occur
      for the first time in middle and old age. In many cases these transient events
      are migraine auras. An aura is a transient, stereotypical, visual or neurological
      episode usually lasting 4 to 60 minutes in duration. Migraine is usually, but not
      always, associated with headache and can be accompanied by systemic and autonomic
      symptoms. Diagnosis is dependent on International Headache Society criteria. The
      pathophysiology is believed to involve neurovascular mechanisms. There is a
      hereditary component to migraine. When migraine auras occur in the absence of
      headache they are termed acephalgic migraines. Late onset migraine accompaniment
      is an acephalgic migraine that presents in middle-aged and older adults. It is
      usually benign. Migraines can be mimicked by other more serious conditions. Most
      patients with a stable migraine pattern and normal neurological evaluation do not
      require further testing. Some patients with atypical presentation, older age, or
      suspected secondary causes need further investigation.

PMID- 15513009
TI  - Topical phenylephrine may result in worsening of visual loss when used to dilate
      pupils in patients with vaso-occlusive disease of the optic nerve.
AB  - Four patients (age range 54-82, 1F 3M) diagnosed with non-arteritic ischemic
      optic neuropathy experienced acute worsening of visual function after
      instillation of phenylephrine for dilated funduscopic examination. They
      experienced decreased visual function immediately or shortly after administration
      of topical mydriatic drops given in preparation for funduscopy. In all cases one
      drop each of 2.5% phenylephrine and 0.5-1% tropicamide was used. Three patients
      had classical risk factors such as hypertension, diabetes, and had a
      contralateral "disc-at-risk". The female and youngest patient had ischemic optic
      neuropathy presumed secondary to lupus erythematosus. The time from acute visual
      loss to presentation to neuro-ophthalmic care ranged from 1-6 days. The time of
      onset of the decline in visual function varied from 45 minutes (patient with
      lupus) to 12 hours after instillation of mydriatic drops. Visual acuity at
      diagnosis ranged from 20/40-20/400. Phenylephrine is a mydriatic with
      vasoconstrictive properties, which may be absorbed through the cornea, thus
      yielding non-negligible intraocular concentrations. Vasoconstriction of the
      watershed posterior ciliary capillary beds may result in further precipitating
      infarction of already compromised circulatory territories in edematous optic
      nerves. Because phenylephrine is a known vasoconstrictor in vivo and in vitro, it
      is more likely to cause deleterious vasoconstriction and an acute decline in
      visual function in patients with acute ischemic optic neuropathy than
      tropicamide. The routine practice of using phenylephrine to prepare patients for
      funduscopic assessment should be re-examined, particularly in patients with
      ischemic optic neuropathy.

PMID- 15513010
TI  - Optic nerve head drusen.
AB  - Optic disc drusen are congenital and developmental anomalies of the optic nerve
      head seen commonly in clinical practice, often as an incidental ophthalmologic
      finding during routine exams. Optic disc drusen are a form of calcific
      degeneration in some of the axons of the optic nerve. Visual acuity is often not
      affected but the visual fields of these patients can be abnormal and deteriorate
      over time. Optic disc drusen are familial and are not uncommon. They are thought
      to be the result of pathology at the level of the optic nerve head itself. The
      diagnosis can be made with clinical findings combined with B scan ultrasound and
      computed tomography. In addition, newer modalities using optic nerve head
      tomography are proving to be very useful. Since children as well as adults are
      affected, it is important to consider optic nerve head drusen in the differential
      diagnosis of papilledema or optic nerve swelling.

PMID- 15513011
TI  - Thyroid eye disease.
AB  - Thyroid eye disease remains one of the most common orbital abnormalities
      encountered by ophthalmologists. While the maintenance of thyroid function
      remains of paramount importance to the patient's health, the appearance of the
      orbit, including the eyelid position and position of the globe, proptosis,
      remains of paramount importance to the patient. Following stabilization of the
      condition of the globe in the patient with thyroid eye disease, attention is then
      focused on the rehabilitation of the thyroid orbit. The etiology, diagnosis, and
      management of thyroid eye disease are discussed.

PMID- 15513012
TI  - Diabetic macular edema: classification, medical and laser therapy.
AB  - PURPOSE: to propose and describe a new classification of diabetic macular edema
      (DME) based on its etiopathogenetic features and to present efficacy and safety
      data on medical and laser treatments currently used and under investigation.
      METHODS: available literature on DME has been reviewed and information provided
      by contact lens biomicroscopy, fluorescein angiography and optical coherence
      tomomography has been combined; published data from trials and reports
      investigating effectiveness of medical and laser treatments were also analyzed.
      RESULTS: DME was classified according to its main etiopathogenetic components:
      prevalently retinovascular, tractional and with taut attached posterior hyaloid,
      each of them having peculiar aspects on fundus, angiographic and tomographic
      examination. Focal laser treatment remains the only effective intervention, as
      shown by a large randomized controlled trial, but new less-invasive
      photocoagulation strategies (i.e., light laser photocoagulation and subthreshold
      micropulse diode laser) as well as pharmacological approaches (i.e.,
      antioxidants, PKC inhibitors, aldose-reductase and AGE inhibitors, VEGF
      inhibitors, intravitreal triamcinolone) are emerging. CONCLUSIONS: based on our
      review a classification of DME was developed that may prove useful in making the
      appropriate treatment decision; the new laser and pharmacological treatments
      currently investigated are promising and need to be confirmed by large,
      controlled clinical trials.

PMID- 15513014
TI  - Lax eyelid syndrome or 'progeria' of eyelid tissues.
AB  - PURPOSE: The lax eyelid syndrome was described by Van den Bosch and Lemij as an
      uncommon disorder seen in non-obese elderly people and characterised by chronic
      ocular surface irritation symptoms and a "floppy upper eyelid". The authors
      present some new features of the lax eyelid syndrome. METHODS: The authors report
      five patients, belonging to a younger age group, who presented with premature
      laxity of all the eyelid tissues. This caused medial and lateral canthal dystopia
      and eyelid malposition including ptosis, entropion and ectropion. Initial
      surgical correction was often followed by recurrence after some time.
      CONCLUSIONS: The authors highlight the differences between lax eyelid syndrome,
      cutis laxa, floppy eyelid syndrome and the blepharochalasis syndrome and suggest
      that lax eyelid syndrome can be thought of as "progeria" or premature ageing of
      the eyelid tissues to distinguish it clearly from these other conditions.

PMID- 15513015
TI  - Thrombosed orbital varix -- a correlation between imaging studies and
      histopathology.
AB  - A thrombosed varix in the orbit is comparatively rare. Clinical examination alone
      is often inadequate for diagnosis. Radio-logical examination, such as a computed
      tomography (CT) scan of the orbit, is extremely important. Histopathological
      examination (HPE) after excision biopsy can confirm the diagnosis. The present
      authors describe a case of proptosis in the left eye of a 45-year-old man. CT
      scan and HPE supported the diagnosis of a thrombosed orbital varix. This paper
      discusses the use of radiological investigations to supplement a clinical
      suspicion and make the diagnosis. This entity needs to be included in the
      differential diagnosis of proptosis and requires a coordinated approach for
      establishment of the diagnosis.

PMID- 15513016
TI  - Canaliculitis: the incidence of long-term epiphora following canaliculotomy.
AB  - PURPOSE: To review the long-term outcome following surgical treatment for
      canaliculitis. METHODS: All cases of canaliculitis treated surgically from
      January 1995 to December 2001 were identified from theatre records. Case notes
      were reviewed retrospectively looking specifically for delay in diagnosis
      (defined as two or more visits prior to diagnosis), culture results and outcome
      following surgical treatment. Telephonic questionnaires were used to assess the
      incidence of post-treatment epiphora. Symptomatic patients were offered clinic
      appointments for further assessment and management. RESULTS: Fifteen eyes of 15
      patients were identified, 13 were females and 2 males. Mean age was 69.6 years
      (range 45-87 years). One patient had both upper and lower canaliculitis. The
      remaining 14 (93.3%) had lower canaliculitis. Diagnosis was delayed in 7 of the
      15 patients (46.6%). Culture results were positive in 66.6% with Staphylocococcus
      spp. being the most common isolate (26.6%). Actinomyces was isolated in only 2 of
      the 15 cases (13.3%). Conservative treatment had been tried in 5 cases (33.3%).
      All patients had resolution of symptoms following canaliculotomy. Epiphora was
      identified in four of the treated eyes on telephonic questionnaires. Of these,
      three eyes had preexisting lacrimal pathology. Average follow-up was 26 months
      (range 6-83 months). CONCLUSION: Canaliculotomy is safe and efficacious in the
      treatment of lacrimal canaliculitis with no demonstrable risk of posttreatment
      epiphora.

PMID- 15513017
TI  - Upper lid loading with gold weights in paralytic lagophthalmos: a modified
      technique to maximize the long-term functional and cosmetic success.
AB  - PURPOSE: To describe a modified fixation technique to improve the long-term
      functional and cosmetic success of upper lid loading with gold weights. METHOD: A
      retrospective single surgeon study of combined upper pre-tarsal and direct
      levator fixation of the gold weight. The minimum follow-up period was 12 months.
      RESULTS: Gold weights were implanted with the modified technique into 29
      patients. The gold weight was removed in two cases due to infection and in one
      case due to ptosis. There was no loss of function over the follow-up period and
      the cosmetic outcome was good or very good in all cases. The follow-up ranged
      from 12 to 84 months with a mean of 40 months. CONCLUSIONS: Combined upper pre
      tarsal fixation and direct levator fixation is effective in maximizing both the
      long-term functional and cosmetic success of upper lid loading with gold weights
      in paralytic lagophthalmos.

PMID- 15513019
TI  - Lower eyelid dermatochalasis with massive postural herniation of orbital fat.
AB  - A severe degree of the aging process in the eyelid and orbital soft tissue
      complex can lead to extreme weakness or even dehiscence of the supporting fascia
      and other surrounding soft tissue, rarely leading to free mobility of the orbital
      fat pads and hence postural herniation into the eyelids as seen in this unusual
      case.

PMID- 15513018
TI  - Cavernous hemangioma of the orbit: analysis of 214 cases.
AB  - The records of all patients with orbital cavernous hemangioma managed at
      Zhongshan Ophthalmic Center, Sun Yat-sen University from Jan. 1, 1986 to Dec. 31,
      2000 (n = 214) were reviewed retrospectively. Among them, 126 patients were
      female and 88 were male. The mean age was 39.4 years, ranging from 5.0 to 68.0
      years. The left orbit was affected in 127 cases and the right one in 87 cases. No
      case showed bilateral involvement. A painless, gradually progressive proptosis
      and visual disturbance were the main clinical signs. Ninety-three percent of the
      patients (199/214) could be accurately diagnosed preoperatively based on
      echography and CT/MRI. The tumors were removed successfully by standard lateral
      orbitotomy in 35% (75/214) and by anterior orbitotomy in 65% (139/214). Anterior
      orbitotomy has become an important surgical procedure in the treatment of orbital
      cavernous hemangioma with excellent effect.

PMID- 15513020
TI  - Ocular presentation of sphenoid mucocele.
AB  - A sphenoid mucocele often presents late due to its deep-seated anatomical site.
      It has a varied presentation, due to its close relationship to the cavernous
      sinus and the base of the skull. It can present initially to the ophthalmologist
      with ocular complaints. In the present paper, the authors present two cases of
      sphenoid mucocele, one with an isolated third and one with an isolated sixth
      cranial nerve palsy.

PMID- 15513021
TI  - Endoscopic approach to orbitofrontal cholesterol granuloma.
AB  - A 54-year-old man presented with an orbitofrontal cholesterol granuloma arising
      in the left frontal bone and abutting the dura. The lesion was successfully
      removed with an anterior orbitotomy via a superior lid crease incision. A 70
      degree rigid endoscope was used to visualize removal of the granuloma from the
      inner surface of frontal bone and the dura. The patient made an uncomplicated
      recovery and there was no recurrence at two years follow-up. A combined anterior
      orbital and endoscopic approach may be an alternative to either frontal
      craniotomy or lateral orbitotomy in selected cases of orbitofrontal cholesterol
      granuloma.

PMID- 15513022
TI  - A report of canine tooth syndrome.
AB  - The authors describe the case of a 5-year-old girl traumatized from a dog bite to
      the superior aspect of the orbit in the right eye. The dog's canine tooth
      penetrated deep into the posterior orbit and severed the attachment of the
      superior oblique muscle from the globe posterior to the trochlea. The management
      and clinical course of the patient are described and photographs documenting the
      initial ocular damage and postoperative course are provided. In addition, the
      entity known as 'canine tooth syndrome' is reviewed.

PMID- 15513023
TI  - Isolated neurofibroma of the orbit with extensive myxoid changes: a
      clinicopathologic study including MRI and electron microscopic findings.
AB  - Isolated orbital neurofibroma (INO) without systemic neurofibromatosis is rare.
      Previous reports including MRI with elaboration of the ultrastructural features
      of the cellular and extracellular components in INO do not exist. A 44-year-old
      male presented with painless, slowly progressive proptosis (6 mm) and downward
      displacement (3 mm) of the left eye of two years duration. MRI revealed a
      suprabulbar mass hypointense to fat, isointense to brain on T1-weighted images
      with small hyperintense areas following contrast enhancement. T2-weighted images
      showed a predominantly hyperintense mass with a few hypointense islands. The
      lesion was excised using an anterior superior transseptal orbitotomy.
      Histopathologically, large areas of a paucicellular myxoid stroma containing
      mucopolysaccharides made up approximately three-quarters of the mass. Focal
      hypercellular areas showed marked collagen deposition. Blood vessels were
      distributed at the periphery of the lesion and in association with nodules of
      nerve sheath cells. Ultrastructurally, perineural and fibroblast-like cells were
      loosely arranged in a myxoid stroma. Schwann cells were embedded in a dense
      collagenous matrix. Variable differentiation of Schwann cells, perineural cells
      and fibroblast-like cells associated with a more solid (collagenous) or loose
      (myxoid) extracellular matrix may determine the characteristic, though not
      specific, MRI features in isolated neurofibromas of the orbit.

PMID- 15513026
TI  - Handedness and eye-dominance: a meta-analysis of their relationship.
AB  - About one in ten people is left-handed and one in three is left-eyed. The extent
      of the association of handedness and eyedness is unclear, as some eyedness
      measures are potentially contaminated by measures of handedness. A meta-analysis
      of hand-eye concordance in 54,087 subjects from 54 populations, found that
      concordance was 2.69 x greater in questionnaire rather than performance studies,
      1.95 x greater in studies using unimanual monocular performance measures, and
      6.29 x greater in studies using non-sighting measures of eye-dominance. In the
      remaining studies, which seemed to show no evidence of bias, the odds-ratio for
      hand-eye concordance was 2.53 x; in a population with 9.25% left-handedness and
      36.53% left-eyedness, 34.43% of right-handers and 57.14% of left-handers are left
      eyed. This pattern of hand-eye association poses problems for genetic models of
      cerebral lateralisation, which must invoke pleiotropic alleles at a single locus
      or epistatic interactions between multiple loci. There was no evidence that the
      incidence of eyedness, or the association between eyedness and handedness,
      differed between the sexes.

PMID- 15513024
TI  - Upper and lower eyelid reconstruction for severe disfiguring necrobiotic
      xanthogranuloma.
AB  - BACKGROUND: Necrobiotic xanthogranuloma is a rare disease featuring generalized
      xanthomatous inflammatory skin lesions associated with paraproteinemia and
      possible lymphoproliferative diseases. Eyelid involvement can be unilateral or
      bilateral and ranges from minor xanthelasma-like lesions to severe ulcerative
      disease with consecutive keratitis and scleritis. CASE REPORT: The authors report
      the case of a 67-year-old woman with extensive necrobiotic xanthogranuloma
      involving the eyelids, head and neck, anterior chest, and both upper and lower
      extremities. Periorbital involvement caused severe upper and lower lid ectropium
      with chronic conjunctival inflammation and unilateral exposure keratitis. During
      a persistent period of low disease activity, granulomatous lesions and scars were
      widely excised, lids partially shortened and large full-thickness skin grafts
      applied. Uninvolved parts of the upper arms had to serve as donor sites, as other
      possible donor sites were not available. After successful reconstruction of the
      left side and no local recurrence of the disease, the right side was corrected in
      the same way. Full eyelid closure was achieved and skin grafts healed without
      complications. No recurrence of the disease appeared at the sites of operation,
      despite continuous new lesions elsewhere. CONCLUSION: Severe cicatricial eyelid
      deformation caused by necrobiotic xanthogranuloma can be treated with success by
      excision and free skin grafting. The mechanisms of recurrence at excision sites
      described by others remain unclear, but at least during phases of low activity,
      the described treatment is safe and recurrence is not to be expected.

PMID- 15513027
TI  - Attempts to switch the writing hand: relationships to age and side of hand
      preference.
AB  - The recent suggestion that left-handedness is a mortality risk factor has
      prompted extensive media attention and has renewed research interest in
      generational differences in hand preference incidence and training. It is argued
      that differential generational training effects (the modification hypothesis),
      rather than decreased survival fitness (the elimination hypothesis), account for
      the lower numbers of individuals classified as left-handers in contemporary
      samples over the age of 60 years. A total of 633 individuals (aged 13-83 years)
      were queried about attempts to switch hand preference. Forty-one (6.5%) described
      efforts to shift preference in the rightward direction; of these, 21 (3.3%)
      reported attempted rightward writing hand shifts. The percentage of older adult
      left-handers, who reported right shifts in writing, was greater than the
      percentage of younger left-handers who described such attempts. Comparisons
      between the group reporting right shifts and those reporting no shift experiences
      suggested that the age-related decrease in leftward preference was specific to a
      decrease in the incidence of left-hand writing among older adults.

PMID- 15513028
TI  - Howzat?! Why is there an over-representation of left-handed bowlers in
      professional cricket in the UK?
AB  - An analysis of the bowling action of professional cricketers in the UK for four
      seasons between 1981 and 1991 shows there to be a significant association between
      handedness and bowling style (seam or spin bowling). Furthermore, there is a
      significantly higher number of left-handed spin bowlers than would be predicted
      from the general population, but not left-handed seam bowlers. As the technical
      differences between left- and right-handed orthodox spin bowlers are much greater
      than those between left- and right-handed seam bowlers, these data are consistent
      with the view that the over-representation of left-handed bowlers reported by
      Wood and Aggleton (1989) is due to strategic rather than neuropsychological
      factors.

PMID- 15513029
TI  - On the magnitude of laterality effects and sex differences in functional
      lateralities.
AB  - In the last 20 years, the hypothesis that men and women differ in functional
      lateralities has been used to account for sex-related differences in verbal and
      spatial skills. However, this hypothesis has not been clearly supported, with
      some reviewers confirming it (McGlone, 1980 for example), and others rejecting it
      (Fairweather, 1982 for example). The purpose of the present study was to provide
      a definite test of this hypothesis and to estimate the magnitude of overall
      laterality effects by means of a meta-analytic procedure. A total of 396
      significance levels from a variety of studies on functional asymmetries utilising
      auditory, visual, or tactile presentation of verbal or nonverbal stimuli were
      sampled. Results showed that laterality effects tend to be large and significant
      but that they are heterogeneous in the visual modality. Homogeneity was generally
      achieved by a partition of the studies in terms of the specific task used. The
      results also showed sex differences to be significant in two modalities (visual
      and auditory). The data indicated the presence of sex differences in favour of
      men in functional asymmetries. However, it appears that the findings are not
      resistant to the file drawer problem. The results are discussed with regard to
      their implications for explanations of individual differences in cognitive
      abilities. The relation between functional lateralities and anatomical
      asymmetries is also discussed.

PMID- 15513031
TI  - Temporal processing asymmetries between the cerebral hemispheres: evidence and
      implications.
AB  - This paper reviews a large body of research which has investigated the capacities
      of the cerebral hemispheres to process temporal information. This research
      includes clinical, non-clinical, and electrophysiological experimentation. On the
      whole, the research supports the notion of a left hemisphere advantage for
      temporal resolution. The existence of such an asymmetry demonstrates that
      cerebral lateralisation is not limited to the higher-order functions such as
      language. The capacity for the resolution of fine temporal events appears to play
      an important role in other left hemisphere functions which require a rapid
      sequential processor. The functions that are facilitated by such a processor
      include verbal, textual, and fine movement skills. The co-development of these
      functions with an efficient temporal processor can be accounted for with
      reference to a number of evolutionary scenarios. Physiological evidence favours a
      temporal processing mechanism located within the left temporal cortex. The
      function of this mechanism may be described in terms of intermittency or
      travelling moment models of temporal processing. The travelling moment model
      provides the most plausible account of the asymmetry.

PMID- 15513032
TI  - Handedness as a predictor of increased risk of knee, elbow, or shoulder injury,
      fractures and broken bones.
AB  - Several recent studies suggest that left-handers have higher susceptibility to
      accidental injury. Two studies investigated the suggested link between
      sinistrality and accidental injury by assessing the prevalence of joint problems,
      bone breaks, and fractures, which may be the sequelae of such mishaps. Study 1
      used retrospective responses on medical history checklists completed by 1064
      males on active duty with the United States Air Force. It found that left-handers
      were at significantly higher risk for knee problems (RR = 2.74), elbow and
      shoulder problems (RR = 3.03), and also swollen and painful joints (RR = 1.87),
      although there was no difference in the incidence of broken bones. Study 2 used
      an expanded handedness scale and retrospective reports of both bone breaks and
      fractures in a predominantly university sample of 1716 (975 women, 741 men) with
      median age of 20 years, and demonstrated that non-right-handers were at greater
      risk for bone breaks and fractures (RR = 1.24). As joint problems, as well as
      bone breaks and fractures, are often the aftermath of accidents that result in
      falls or collisions with unyielding objects, the fact that left-handers are more
      likely to suffer from these problems is consistent with the suggestion that
      sinistrals are more susceptible to accident-related injuries.

PMID- 15513033
TI  - Direction and reliability of head tilt in humans.
AB  - It has been proposed that asymmetry in the inner ear underlies various
      manifestations of brain-behaviour asymmetry in the human. Specifically, Previc
      (1991) argued that an otolith imbalance manifests itself in an asymmetrical head
      posture, and later (1994) suggested that head tilt may be consonant with other
      measures of human laterality. The present study tested the reliability of head
      tilt across days and assessed its relationship with handedness, footedness, and
      eyedness. As in Previc's earlier studies, a majority of our subjects tilted
      rightward. Head tilt proved to be highly stable across days but was not
      correlated with the other laterality measures. These findings suggest that head
      tilt may reflect an underlying asymmetric substrate that appears not to be
      directly related to other measures of cerebral hemispheric dominance.

PMID- 15513034
TI  - Rotational bias in mosquitofish (Gambusia holbrooki): the role of laterality and
      sun-compass navigation.
AB  - Spontaneous rotational preferences in swimming of mosquitofish (Gambusia
      holbrooki) were investigated. Females, but not males, swam in circular tanks
      preferentially anticlockwise in the afternoon but not in the morning. Females'
      rotational preferences appeared to be related to a sun-compass orientation
      mechanism, as they disappeared under diffuse lighting conditions and when using
      naive females (i.e. using individuals never exposed to sunlight). Under repeated
      testing, however, the bias produced by the sun-compass mechanism tended to
      disappear, but females still showed rotational preferences that became stable and
      consistent at the individual level. Males too showed consistent individual
      rotational preferences under repeated testing. It is concluded that rotational
      bias in mosquitofish is due to two independent phenomena: a sun-compass
      navigation mechanism, which is related to the intensity of predation, and a
      behavioural lateralisation at the individual level, which is likely to reflect
      neural asymmetries in motor or sensory systems.

PMID- 15513035
TI  - Left-handedness and age: comparing writing/ drawing and other manual activities.
AB  - The percentage of individuals who use the left hand for writing/drawing, brushing
      teeth, and throwing a ball was compared in 3229 subjects ranging in age from 8 to
      96 years. The "elimination" versus "modification" hypotheses were tested as
      explanations of prior observations that there are fewer left-handers among the
      elderly. These hypotheses predict different numbers of left-handed elderly
      individuals when measured by activities not influenced by social pressure. The
      results suggest that there are age-related patterns among different measures of
      left-handedness. However, a significant decline in left-handedness among the
      elderly was also found when measured by less culturally determined activities.

PMID- 15513036
TI  - Dermatoglyphic asymmetry is related to perceptual asymmetry and to
      interhemispheric transmission.
AB  - The numbers of ridges on the fingertips is asymmetrical between hands and is also
      sexually dimorphic. Most people have more ridges on the right hand (rightward
      dermatoglyphic asymmetry; R >) and men typically have more ridges than women. The
      direction of dermatoglyphic asymmetry has been shown to be related to patterns of
      cognitive abilities in men and women and to perceptual asymmetry in homosexual
      men. W e assessed presumptively heterosexual, right-handed men and women who had
      either R > (n = 35) or L > (n = 30) ridge count, on: (1) dichotic listening to
      words; (2) two tachistoscopic tasks sampling visual field asymmetries (dot
      location and letter identification); and (3) a tachistoscopic task designed to
      examine interhemispheric transmission. L > subjects had a smaller right-ear
      advantage than R > subjects, but this was accounted for by an increased incidence
      of an atypical left-ear advantage in the L > group. Visual field asymmetries were
      also smaller in the L > group but the asymmetry measures did not reach
      significance, with the exception of an increased incidence of an atypical field
      advantage (left) for letter recognition only. On the interhemispheric transfer
      task, L > subjects performed relatively faster on tasks requiring
      interhemispheric comparisons than did R > subjects. These findings confirm an
      association between the direction of dermatoglyphic asymmetry and aspects of
      brain organisation.

PMID- 15513037
TI  - Foot laterality in children, adolescents, and adults.
AB  - This investigation reviewed 14 studies describing the trichotomous distribution
      of foot preference behaviour spanning early childhood to adult years. Findings
      suggest that a substantially greater percentage of children are mixed-footed in
      comparison to older individuals. A significant shift towards right-sidedness
      appears to occur sometime during late childhood, after which, behaviour remains
      relatively stable. The incidence of left-footedness is similar across the
      lifespan. In comparison to handedness, substantially more (about twice as many)
      young children are mixed-footed compared to mixed-handed. A similar pattern is
      noted during adolescence and adulthood, but the differences are smaller. Values
      for leftsidedness (upper and lower limbs) are comparable across the lifespan. Of
      the existing theoretical models, Annett's Right-shift hypothesis with additional
      propositions related to environmental influences (Collins, 1977; Porac, 1993;
      Provins, 1992) provides partial explanation for the findings.

PMID- 15513038
TI  - Hand and foot preference in young and older adults: a comment on Gabbard and
      Iteya.

PMID- 15513039
TI  - Auditory lateralisation: shifts in ear use during attachment in the domestic
      chick.
AB  - Chicks were imprinted to the sound of a cluck, by differing durations of exposure
      in the dark on the first day of life. At test, when the chicks were placed
      centrally in an arena lit only by infra-red, those receiving two or three hours
      of exposure turned their right ear towards a source of clucks, just before
      approach to the source, but used their left ear instead after five or six hours
      exposure; after four hours there was no clear bias. This shift was not due to
      differences in age nor in time of day, but was a direct consequence of
      lengthening prior exposure. As learning about (and/or attaching to) the cluck
      progresses, there thus appears to be a shift from predominant use of the left
      hemisphere in listening and responding to the cluck. There is other evidence that
      the left hemisphere may be particularly involved in the chick in initial
      selection of important cues, while the right hemisphere elaborates relatively
      unselected records.

PMID- 15513040
TI  - Differences in hemispheric asymmetry between dyslexic and normal children on a
      lateralised lexical decision task.
AB  - The present experiment was conducted in order to further investigate the
      relationship between deficits in left hemisphere processing and phonetic decoding
      in dyslexic children. We administered a lateralised lexical decision task that
      manipulated wordness, length, and word regularity of grapheme-phoneme conversion.
      Right-handed male dyslexic children and normal control children were presented
      with words and pronounceable nonwords. Although there were no overall differences
      in hemispheric asymmetry between the groups, they did differ in laterality
      effects in accuracy when responding to nonwords and to phonetically regular
      words, with the normal children showing the right visual field advantage/
      sensitivity (left hemisphere dominance/sensitivity), while the dyslexics failed
      to show any visual field advantage or sensitivity for these stimuli. Further,
      group differences were observed in left but not right hemisphere functioning. The
      results suggest that deficits in left hemisphere processing are apparent only
      when the dyslexics are attempting to utilise the rules of phonics. Support for
      the use of this paradigm for use with dyslexic children is also discussed.

PMID- 15513043
TI  - Accuracy of college students' reports of parental handedness.
AB  - College students' reports of their parents' handedness were compared with data
      provided by the parents themselves. The students' reports of their parents'
      writing hand were highly accurate, the reports of their parents' general
      handedness somewhat less so. For the latter measure, the students were asked,
      ''What is your mother's (father's) handedness?'' and were given the choice
      ''left'',''either'', ''right'',and ''don't know''. Their answers were then
      compared with the investigators' classification based on the parents' answers to
      a 10-item hand-use questionnaire. For this measure, the accuracy of the students'
      reports was also found to be related to the students' own handedness.

PMID- 15513044
TI  - Visual field asymmetries in schematic persistence.
AB  - A modified partial-report technique was used as a tool to study hemispheric
      asymmetries in schematic persistence. Two types of stimuli were presented: (1)
      verbal stimuli consisting of function words and nonsense words, and (2) pictures
      of faces and nonfaces. The stimulus items were arranged bilaterally in a circular
      array around the fixation point and the participants' task was to decide whether
      the probed item was a correct or distorted version of each stimulus type. Delay
      time between stimulus set and marker ranged from 0 ms to 360 ms. Calculating a
      sensitivity measure of accuracy, distinctive visual field differences emerged
      which depended on the nature of the stimuli; that is, a left field advantage for
      facial stimuli and a right field advantage for lexical stimuli. In addition,
      performance decreased linearly as delay time between probe and marker increased.
      The present results indicate that on a level of schematic persistence perceptual
      hemispheric asymmetries are already strongly present.

PMID- 15513045
TI  - Interhemispheric cooperation of left- and right-handers in mental calculation
      tasks.
AB  - Relations between handedness and interhemispheric processing in cognitive tasks
      were examined. Thirty six right-handers and thirty left-handers (familial and
      nonfamilial left-handers) were asked to add two numbers which were presented
      tachistoscopically. Two numbers were displayed either to one visual field, or one
      to the left and one to the right visual field simultaneously. In Experiment 1,
      the numbers were displayed in Arabic numerals, and in Experiment 2 one of the
      numbers was displayed in Kanji and one in Arabic numerals. The results of
      Experiment 1 showed a bilateral advantage, however no subject group difference
      was shown in the performance of the three (left unilateral, right unilateral, and
      bilateral) presentation conditions. Though familial left-handers showed a weaker
      tendency to different patterns than right and non-familial left-handers, the
      results of Experiment 2 were largely similar to those of Experiment 1. These
      findings suggest that interhemispheric processing may not differ between left-
      and right-handers.

PMID- 15513046
TI  - A model for human situs determination.
AB  - Alterations of human laterality range from situs reversal or consensus isometry
      to isolated anomalies of the cardiac, respiratory, gastrointestinal, skeletal,
      and central nervous systems. A mechanism for human situs determination has been
      derived from the general model of Brown and Wolpert (1990) , with steps involving
      A-P axis, D-V axis, midline, global situs, and local situs specification.
      Comparison with Drosophila segmentation is supported by maternal transmission of
      certain human situs defects and mutation of appropriate Drosophila gene
      homologues in the human Waardenburg and Greig syndromes. Anteroposterior
      gradients in expression of vertebrate homeotic genes may relate to a proposed
      hierarchy of regional laterality decisions. Early alterations in A-P or D-V axis
      polarity would produce situs reversal in 100 of individuals, as observed in pure
      situs inversus, homozygous inv mice or manipulated Xenopus embryos. Later
      alterations would permit random right-left decisions and account for heterotaxy
      in 50 of affected individuals, as observed in poly asplenia or homozygous iv
      mice. Randomisation of brain asymmetry could explain why situs but not brain
      laterality may be reversed in humans, with forebrain situs reversal or isometry
      leading to brain anomalies. Homologues of Drosophila genes regulating axis
      polarity, heart and gut development are attractive candidates in human laterality
      disorders, but none is uniquely localised to the 6q14-q21 or9q32-q34, 7q22, 10q21
      22, 11q13 or 11q25, 12q13, 13qter, or Xq24-q27.1 chromosome regions highlighted
      by heterotaxic patients or mutant mice.

PMID- 15513048
TI  - Commentary. Left and right in classical Greece and Italy.

PMID- 15513049
TI  - Ocular dominance: some family data.
AB  - The most popular aspect of ocular dominance is sighting dominance or eye
      preference (eyedness). It refers to the preferential tendency of individuals
      looking through a telescope, microscope, or keyhole, or sighting along a gun.
      There is little work on the relative contribution of genetic factors to ocular
      dominance, so it is useful to review the available data from the literature and
      to present some new data. Eyedness was examined in a sample of 292 biologically
      related parent-offspring triads and 36 sibling pairs. The incidence of right
      eyedness amounted to 66.1%. There was a predominance of right-eyed male subjects
      over right-eyed female subjects. Analysis of the family study showed a
      significant correlation between parents and children. The frequency of left
      eyedness increased continuously with the number of left-eyed parents. These
      results imply that a genetic influence may operate to affect the direction of eye
      preference, although the data do not fit any straightforward recessive or
      dominant Mendelian model. It is possible that they are compatible with the type
      of model invoking fluctuating asymmetry which has been used to explain the
      inheritance of other aspects of laterality.

PMID- 15513050
TI  - Examining the stabilising characteristics of footedness.
AB  - The stabilising characteristics of footedness within the contexts of unilateral
      and bilateral preference and performance were examined. Predictions from Previc's
      (1991) theory of prenatal determination of functional asymmetry suggest a
      reliance on the left side of the body for stabilisation regardless of context. To
      test the hypothesis, right- and left-footers (as assessed bilaterally) were
      examined for preference and performance using a one-leg static balance task on a
      force plate in simple and complex conditions. Results indicated that preference
      for stabilisation in the bilateral context was independent of limb choice in the
      unilateral context. That is, the majority of individuals switched limbs for
      stabilisation in the unilateral context (most favoured the right side). These
      findings lead to the conclusion that foot preference may be dependent in part on
      the context of the task and not bound exclusively to neurodevelopmental origins.

PMID- 15513051
TI  - Occupation and dichotic listening performance.
AB  - A previous study has shown that dichotic listening performance was related to
      occupation (Govier & Bobby, 1994). That experiment used subjects drawn from a
      variety of professional occupations. The experiment described here tested the
      dichotic performance of male and female subjects in a single professional
      setting; medicine. Male and female doctors and male and female nurses were tested
      on a dichotic listening task. The results indicated that pattern of dichotic
      performance was more closely associated with occupation than biological sex, and
      were interpreted as supporting the view that both occupational choice and
      dichotic-listening asymmetries depend on biologically determined aspects of brain
      organisation.

PMID- 15513052
TI  - Sex differences in matching circles and arcs: a preliminary EEG investigation.
AB  - Alpha wave (8-12 Hz) activity was monitored over the four lobes of the left and
      right cerebral hemispheres while 12 male and 12 female participants mentally
      manipulated circles and arcs to determine size matches. Four task conditions were
      tested, each designed to tap into the visual encoding, image generation, mental
      rotation, and comparison/decision subcomponents comprising this task. Males were
      more accurate than females in making such matches, and in all conditions they
      exhibited a significant alpha power reduction asymmetry, with the right frontal
      lobe being more active than the left frontal lobe. Females showed a pattern of
      activation that was bilaterally distributed, primarily to the frontal and
      temporal regions. These findings suggest a difference in the functional
      organisation of the male and female brain which may contribute to the reported
      sex difference in the performance of some spatial tasks.

PMID- 15513053
TI  - Pawedness and motor asymmetries in toads.
AB  - Pawedness was investigated in three species of toads, Bufo bufo , Bufo viridis ,
      and Bufo marinus. Samples from natural populations were collected in two
      successive years and tested during attempts to remove a strip of paper stuck onto
      the snout ( Bufo bufo and Bufo viridis ) or during attempts to remove an elastic
      balloon wrapped around the head ( Bufo bufo ). A preferential right forelimb use
      at the population level was observed in Bufo bufo in both tests, whereas no clear
      pawedness was observed in Bufo viridis. Bufo marinus also showed no laterality in
      the paper-strip test, but it appeared to be strongly lateralised in another test
      that investigated which side the toad rotated when turned on its back underwater.
      Preferentially turning to the toad's left side as part of a righting response,
      Bufo marinus released the left forelimb first, using the right forelimb to
      control the roll to the upright position, and push to the surface. These results
      suggest that preferential limb use has a long evolutionary history, which dates
      back to early tetrapods.

PMID- 15513054
TI  - Posture and reaching in tufted capuchins (Cebus apella).
AB  - This research investigated the effects of posture on lateral bias for food
      reaching in tufted capuchin monkeys ( Cebus apella ) by comparing hand
      preferences for quadrupedal and bipedal reaching. Several findings of this
      investigation warrant discussion. First, we found a population-level bias towards
      use of the right hand for bipedal reaching but not for quadrupedal reaching.
      Second, adults exhibited a greater right-hand preference for bipedal reaching
      than did immatures. Third, subjects showed a greater right-hand preference, and a
      greater strength of preference independent of direction, for bipedal reaching
      than for quadrupedal reaching. Fourth, we found a significant positive relation
      between the direction of hand preference for quadrupedal and bipedal reaching. We
      believe that capuchins provide an alternative primate model to chimpanzees for
      the evolution of human bipedalism and right-handedness. One implication of this
      model is that right-handedness emerged in hominids prior to extensive expansion
      of brain size and elaboration of material culture.

PMID- 15513056
TI  - Commentary. Fractionating handedness in mental retardation: what is the role of
      the cerebellum?

PMID- 15513057
TI  - Do anomalies of handedness exist in children with Fragile-X syndrome?
AB  - Hand preference and skill were assessed in 27 children with Fragile-X syndrome,
      30 children with Down's Syndrome, and 29 normal developing children. Three
      separate and specific anomalies of handedness that have been reported in other
      learning-disordered groups were examined: increased incidence of left-handedness;
      ambiguous or inconsistent handedness; and preference-skill discordance. The
      results revealed no difference between the subject groups in the distribution of
      left-handedness or ambiguous handedness. The main differences was the percentage
      of children who were discordant for hand preference and hand skill. In the
      Fragile-X group 37% preferred to use their right hand but demonstrated no overall
      difference in skilled performance between the hands. In contrast, only 13% of
      children with Down's Syndrome and 17% of normal controls showed this pattern of
      hand discordance. The results are discussed in the context of past research that
      has shown a similar dissociation of preference and skill in children with autism.

PMID- 15513058
TI  - Do unilateral lesions of the developing brain have side-specific psychiatric
      consequences in childhood?
AB  - This study used a large epidemiological sample of children with lateralised brain
      lesions to establish whether damage to the developing human brain has side
      specific psychiatric consequences. Parents and teachers completed behaviour
      questionnaires on 429 hemiplegic children and teenagers, with a subsample of 149
      hemiplegic children also being assessed by parent and child interviews. Although
      childhood hemiplegia was accompanied by a high rate of psychopathology, children
      with right- and left-sided hemiplegias did not differ significantly on any
      dimensional or categorical measure of psychopathology. This absence of laterality
      effects, perhaps reflecting the developing brain's neuroplasticity, casts doubt
      on theories linking particular types of child or adult psychopathology to side
      specific damage to the developing brain.

PMID- 15513059
TI  - Unimanual and bimanual simultaneous fingertapping in schoolchildren:
      developmental aspects and hand preference-related asymmetries.
AB  - Computerised analysis of finger tapping was performed in 233 normal 5- to 12-year
      old children whose hand preference was assessed with six demonstration actions.
      Performance with both hands became more rapid with age when tapping unimanually
      or simultaneously in phase with two hands as quickly as possible. There were no
      differences between the sexes. Performance with both hands also acquired more
      tapping regularity with age during unimanual tapping, whereas only the left hand
      did so during bimanual tapping. There was no age effect on the dexterity (speed)
      difference between unimanually tapping hands, nor on the relative time lag and
      the degree of synchrony between the hands in bimanual tapping. The degree of
      synchrony, however, becomes more stable in older children. The more righthanded
      children are, the faster the right hand is in unimanual tapping, and the more the
      right hand is ahead of the left hand during bimanual tapping. However, there is a
      right shift for both of these variables which makes them poor predictors of hand
      preference. These results suggest that there is a strong bias towards the right
      hand in complete righthanders as well as--to a lesser extent--in all others,
      which might be connected to the leading role of the left hemisphere for the
      performance aspects of hand motor function under study.

PMID- 15513060
TI  - Handedness scale: how many and which items?
AB  - A stepwise analysis of the Cronbach Alpha Coefficient (CAC) was performed on five
      large samples of adults and young children, in order to choose the ''minimum''
      set of items of a handedness scale which gives the maximum reliability. In
      adults, a handedness scale with 12 items has nearly the same or even a better CAC
      than other scales with more items; so, a choice of 10 to 12 items seems to be
      adequate. For children, a scale with eight items seems to be quite reliable but
      it is not impossible that a scale including more items would lead to a slight
      increase of CAC. The controversial usefulness of a precise assessment of the
      ''general handedness factor'' (the first principal component) generated by
      handedness questionnaires and its J-shaped distribution in the general population
      are discussed.

PMID- 15513061
TI  - Lateral biases in aesthetic preferences: pictorial dimensions and neural
      mechanisms.
AB  - Observers often prefer one orientation of a stimulus over its mirror image; these
      lateral biases are assumed to reflect aspects of the observer's neural
      organisation. However, the precise dimensions of pictorial organisation that
      influence these preferences, as well as the underlying neural mechanisms, are not
      clear. The present experiments addressed these issues by employing a stimulus set
      allowing for a factorial combination of three dimensions of pictorial
      organisation: Weight, Interest, and Directionality. Experiments 1 and 2 found
      that subjects exhibited robust and consistent preferences for stimuli with left
      to-right directionality, especially for stimuli with left-biased interest; right
      biased interest eliminated the preference for left-to-right directionality. The
      dimension of weight had little effect. Inter-task correlations from Experiment 3
      suggested that this preference for left-to-right directionality (i) reflects a
      stable, underlying directional bias in perceptuo-motor processing, and (ii) is
      not related to individual differences in hemispheric activation.

PMID- 15513062
TI  - Hemispheric specialisation in animals and humans: introduction.

PMID- 15513063
TI  - Left and right hemisphere memory traces: their formation and fate. Evidence from
      events during memory formation in the chick.
AB  - In the domestic chick, different versions of a particular learning experience are
      elaborated by right and left hemispheres (left: selection of cues allowing
      selection of appropriate response; right: elaboration of relatively complete and
      unselected record). During memory formation, further processing of the traces is
      associated with a series of brief points of trace reactivation, which recur with
      differing periodicity in association with the two hemispheres (16 min: left; 25
      min: right). As a result there is a series of near coincidences, which allow
      interaction between the two traces. The first, at 48-50 min, is associated with
      such marked changes in what is available to recall that it has been identified as
      the onset of long-term memory. The period is shown here to begin with a left
      hemisphere event, which overlaps with a right hemisphere event, beginning at 50
      min, in a way that helps to explain why the interaction that occurs at this time
      is predominantly one in which the left hemisphere accesses right hemisphere
      material. It is argued that the main change during hemispheric interaction is the
      establishment of linkages between different trace ''fragments''.

PMID- 15513064
TI  - Early experiential effects on laterality: research on chicks has relevance to
      other species.
AB  - The influence of early experience on the development of lateralisation of
      hemispheric function was further investigated, using the chick as a model. A
      range of functions are lateralised in the chick and these correlate with
      asymmetry in the organisation of the visual projections. Chicks using the right
      eye and, therefore, primarily the left hemisphere are able to switch from pecking
      randomly at grain and pebbles to pecking mainly at grain, whereas those using the
      left eye and primarily the right hemisphere continue to peck at random. Exposure
      to light during the last days of incubation establishes this lateralisation in
      males, as a consequence of the embryo being oriented in the egg so that the left
      eye only is occluded. Males incubated in the dark peck at random when using
      either the right or left eye. Irrespective of light experience, females perform
      the same as dark-incubated males: they are not influenced by light exposure.
      Monocular performance of the pebble-grain task is compared to binocular
      performance, and the sensitive period for the influence of light is delineated.
      The interactive effects of sex hormone levels on the differentiation of
      lateralisation are discussed and also the relevance of the results to other
      species, including humans.

PMID- 15513065
TI  - The effects of early environment on the development of functional laterality in
      Morris maze performance.
AB  - The current study examined the contribution of early postnatal experience to the
      functional lateralisation of spatial ability in the male rat. Litters were
      handled (H) or non-handled (NH) during the first 20 days of life, and three males
      from each litter were tested in the Morris water maze in adulthood. Two subjects
      from each litter were monocularly tested, one with the right eye patched and the
      other with the left eye patched. A third subject in each litter was tested with
      both eyes open. Handling interacted with Eye Patch for time and distance
      measures. Performance of Right- and Left-Patched rats was equivalent for the NH
      group, but the H subjects tested with the Right Patch outperformed H subjects
      with the Left Patch. These results confirm studies that found spatial navigation
      performance to be lateralised to the right hemisphere in male rats. The data
      indicate that functional asymmetry of spatial navigation behaviour in the adult
      male rat is sensitive to environmental influences during early development.

PMID- 15513066
TI  - Hemispheric lateralisation and global precedence effects in the processing of
      visual stimuli by humans and baboons (Papio papio).
AB  - This paper examines the effect of global precedence (GPE: Navon, 1977) and its
      lateralisation from a comparative perspective. Using a divided field matching-to
      sample task with compound stimuli, Experiment 1 demonstrated consistent patterns
      of lateralisation in humans and baboons, corresponding to a right-hemisphere
      advantage for global processing and a left- but nonsignificant advantage for
      local processing. Species differences emerged in terms of GPE; humans showed a
      global precedence effect, and baboons were better for local than for global
      matching. In Experiment 2, a visual search task was used to assess the origin of
      species differences in terms of GPE. Humans processed the global structure of the
      forms pre-attentively, whereas baboons used an attentional search strategy. From
      this finding, it is argued that lateralisation in Experiment 1 was rooted in
      early perceptual mechanisms. So far, consistent patterns of lateralisation for
      global/local processing have been found in baboons, chimpanzees, and humans,
      suggesting that this phenomenon has a long evolutionary history.

PMID- 15513067
TI  - Manual exploratory procedures and asymmetries for a haptic search task: a
      comparison between capuchins (Cebus apella) and humans.
AB  - Left-hand preferences in monkeys (capuchins, macaques) for haptic discriminations
      have been taken to indicate that the right hemisphere is more involved than the
      left hemisphere in solving these tasks. We confirmed this left-hand bias in a
      group of 21 capuchins haptically searching for sunflower seeds located in
      crevices in 12 different objects (Lacreuse & Fragaszy, 1996). In an attempt to
      specify the relations of the left-hand bias to hand performance and hemispheric
      lateralisation, we analysed the manual exploratory procedures used by the
      subjects when exploring the objects, and compared them to those of humans
      confronted with the same task. All the hand-movement patterns displayed by humans
      were also observed in capuchins, but humans performed exhaustive explorations,
      whereas capuchins restricted their haptic investigations to limited portions of
      the objects. Both species adopted several ''exploratory procedures'' to
      investigate particular objects. Although capuchins showed a left-hand preference
      to perform the task, finer analyses of haptic exploratory procedures revealed no
      difference in the way the left and right hands explored the objects, nor in the
      efficiency with which each hand solved the task. Nor was any measurable
      difference in manual exploratory procedure and efficiency found in humans. The
      discussion emphasises the need to complement measures of manual preference with
      finer indices of hemispheric lateralisation, for a better understanding of
      functional asymmetries in primates.

PMID- 15513068
TI  - Manual specialisation and tool use in captive chimpanzees (Pan troglodytes): the
      effect of unimanual and bimanual strategies on hand preference.
AB  - Hand preference for tool use was assessed in a sample of captive chimpanzees (Pan
      troglodytes). Whether the subjects solved the tool task using either a unimanual
      or coordinated bimanual strategy was manipulated in the chimpanzees. No
      population-level hand preference was found for tool use when unimanual strategies
      were used by the chimpanzees. However, a population-level right-hand bias was
      found when coordinated bimanual actions were required of the chimpanzees. A
      significant correlation was found in hand use for the two hand preference testing
      conditions. Neither sex nor rearing was found to significantly affect the
      direction or strength in hand preference. These results may explain discrepancies
      in hand preference reported in captive and wild chimpanzees with regard to tool
      use and other manual activities.

PMID- 15513069
TI  - Origins and functions of laterality: interactions of motoric systems.
AB  - To evaluate lateral motoric bias in response systems at different levels of the
      neuraxis and assess the extent of interaction between these levels in the small
      eared bushbaby (Otolemur garnettii), 27 animals were tested for lateral bias in
      hand use and whole-body turn bias in two postural conditions. Subjects retrieved
      mealworms quadrupedally by reaching downwards into glass jars and bipedally by
      reaching upwards to baited straws. Eye bias was assessed separately. Behaviours
      were scored from videotape. Two subgroups were identified: SHIFTERS changed hand
      preference with posture and had correlations of hand/eye bias in quadrupedal
      posture and of hand/turn bias, with more bimanual reaching, in bipedal posture;
      NONSHIFTERS were consistent in hand preference and more strongly lateralised in
      reach and turn than SHIFTERS. Subgroups did not differ in reach efficiency.
      Results are interpreted to support the value of the analysis of motoric levels
      and their interactions in the study of the evolution of laterality. Assuming
      natural selection for coordinated and targeted behaviours to be the source of
      lateralisation, several proposals in support of a motoric theory of laterality
      origins and functions are advanced.

PMID- 15513070
TI  - Eye preference patterns among left-handed adults.
AB  - The sidedness congruency of limb (hand and foot) and eye preference was studied
      in a sample of 387 adults, ranging in age from 18-94 years. The sample contained
      approximately equal numbers of right- and left-handers. Results revealed that
      both right- and left-handers displayed a percentage incidence of congruency with
      eye preference that was greater than chance. In addition, the incidence of hand
      eye congruency was higher among older adults. The odds of the occurrence of left
      eye preference were increased in the presence of either left hand or left foot
      preference in all of the age groups studied. The present findings are consistent
      with the results of a recent meta-analysis on the relationship between hand and
      eye preference conducted by Bourassa, McManus, and Bryden (1996); these results
      are also consistent with the idea of a common mechanism underlying limb and eye
      lateral preferences.

PMID- 15513071
TI  - On the genetics and measurement of human handedness.
AB  - Lateral preferences in humans and other primates may be a key to many important
      issues in biology and psychology. There is strong evidence that the
      representation of language functions in the cerebral cortex is different in left
      handed (LH) people than in right-handed (RH) people, and an understanding of
      handedness may lead to valuable clues as to how the brain becomes organised in
      the way that it does. Although there are clearly cultural effects that influence
      manual activities, there is nevertheless evidence that human handedness and other
      lateralities are at least in part genetically determined: compared with two RH
      parents, one RH and one LH parent are 2-3 times more likely to have an LH child,
      and two LH parents are 3-4 times more likely to have an LH child. Thus, one might
      wish to investigate the genetics of laterality with the goal of understanding the
      biological mechanisms that lead to the preferential use of one hand (or eye or
      foot). One may also see links between human handedness and footedness and the
      motor asymmetries found in many nonhuman primate species, and perhaps in lower
      mammals as well. From this perspective, one might see the study of human
      laterality as relevant to evolutionary biology. Investigators of both human and
      nonhuman asymmetries have to grapple with such difficult measurement issues as
      the relations between preference and performance, and the influences of postural
      and task demands, and have much to offer each other in the quest for the nature
      of laterality. Our recent work seems to indicate that the various sensory and
      motor lateralities may be related, in humans, but not in a simple way. In future
      work, the challenge will be to identify the relations between the various
      laterality ''profiles'' and patterns of functional cerebral organisation.

PMID- 15513072
TI  - Effects of facial identity, facial expression, and subject's sex on laterality in
      monkeys.
AB  - Previously we showed that rhesus monkeys processed discriminations of monkey
      faces significantly better with the right hemisphere of the brain than with the
      left. The overall effects of the type of discrimination, i.e. facial identity or
      expression, and the sex of the subject on laterality are examined here for seven
      phases of this series of experiments. Both types of discrimination produced a
      right hemispheric advantage, with slightly greater laterality for expression, but
      generally the laterality did not differ significantly for the two types. Female
      monkeys demonstrated more consistent and significant right hemispheric laterality
      than did males. Furthermore, female monkeys tended to be more lateralised for
      discriminations of expression, whereas males were about equally lateralised for
      both types. Thus, in these experiments the overall right hemispheric advantage
      for facial discriminations in monkeys reflects the contribution of the female
      subjects, especially when discriminating expression, more than that of the males.

PMID- 15513073
TI  - Backward priming and postlexical processing in the right hemisphere.
AB  - Postlexical processing in the intact cerebral hemispheres was studied using a
      divided visual field method. Asymmetrically associated prime-target pairs were
      presented in forward (PRIEST-MAN) and backward (MAN-PRIEST) directions in a
      binary lexical decision task. The primes were presented either centrally or
      laterally, and the targets laterally. The priming effects in the backward
      conditions were assumed to reflect postlexical semantic processing. The analyses
      of response times revealed that, in the left visual field, backward priming was
      equal in both prime conditions, but forward priming was observed for the central
      primes only. In the right visual field, forward priming was similar in both prime
      conditions, whereas backward priming was restricted to the central prime
      condition. The analyses of errors showed an LVF advantage in backward priming and
      a trend towards an RVF advantage in forward priming in central prime conditions.
      The results suggest that the right hemisphere is capable of postlexical semantic
      processing, but may lack an expectancy-based mechanism underlying forward
      priming.

PMID- 15513074
TI  - Footedness is a better predictor of language lateralisation than handedness.
AB  - A tremendous amount of experimental work has attempted to identify a reliable
      behavioural predictor of language lateralisation. Preferred handedness has
      probably received the most attention, but there are some recent reports that
      preferred footedness may serve as a more reliable predictor. The present study
      sought to test this claim by selectively recruiting 32 participants such that the
      factors of handedness, footedness, and gender were completely crossed. Language
      lateralisation was assessed with the Fused Dichotic Words Test (FDWT), and
      lateral preference for both handedness and footedness was assessed using self
      report questionnaires. Ear advantage on the dichotic task varied significantly
      with preferred foot ( P <.001) but not with preferred hand ( P = .196). This
      result is problematic for evolutionary theories of cerebral lateralisation that
      claim left-hemispheric language is related to fine manual motor skill and
      sequencing. Language lateralisation may be more closely related to asymmetrical
      control of whole-body finely sequenced movements.

PMID- 15513075
TI  - Inter-limb coupling in coordinated bimanual movement: attention and asymmetries.
AB  - Inter-limb coupling, a phenomenon whereby each of the upper limbs tends to take
      on characteristics of the intended movement of the other, represents a limitation
      on the ability to perform asymmetrical bimanual movements. Two experiments each
      employing 16 dextral and 16 sinistral normal subjects are reported. In the first
      experiment evidence of inter-limb coupling was observed during a continuous
      bimanual rotary task. This coupling appeared to be asymmetrical, with the
      nonpreferred hand contributing more to coupling than the preferred hand,
      especially in dextrals. In the second experiment asymmetries in inter-limb
      coupling were found to be modified by the conscious direction of attention to one
      or other hand. This suggests that the often reported strong inter-limb asymmetry
      associated with dextrality, and the weaker assymetry associated with
      sinistrality, may be partly due to an underlying inter-limb attentional asymmetry
      in the former, and a relative lack of attentional asymmetry in the latter.

PMID- 15513076
TI  - Description and validation of a flexible and broadly usable handedness
      questionnaire.
AB  - Empirical evidence is provided which shows that handedness questionnaires should:
      (a) comprise items that cover skilled and unskilled activities; (b) be
      sufficiently long to capture a ''mass effect'' of variability in lateral
      preferences over a range of items; and (c) allow graded answer options for
      individual items rather than forced left/right choices. When using questionnaires
      that meet these criteria, it is possible to establish significant correlations
      between hand preference and performance even within a group of right-handers. In
      addition, such questionnaires are flexible enough to accommodate a great variety
      of handedness classification schemes.

PMID- 15513077
TI  - Early studies of eye dominances.
AB  - Early accounts of eye dominances are considered. An index of sighting dominance
      (eye closure) was described by Aristotle, and Porta (1593) introduced an
      alignment test for it. Porta also described rivalry dominance, and asserted that
      it favoured the right eye. Acuity dominance, on the other hand, was assigned to
      the left eye by Borelli (1673). These views are placed in the context of
      prevailing theories of binocular vision.

PMID- 15513078
TI  - Eye preferences in common marmosets (Callithrix jacchus): influence of age,
      stimulus, and hand preference.
AB  - Eye preferences of the common marmoset ( Callithrix jacchus ) were examined,
      taking into account age, arousal, and hand preference. Monocular eye use for
      looking through a small hole at a stimulus was recorded. Of 21 marmosets, 20
      displayed right-eye preferences for viewing a piece of familiar food. In subjects
      tested at 3-8, 12, 15-18, and 22 months, eye preferences were consistent across
      age. A group bias, indicative of right-eyedness, was also found for viewing other
      stimuli. The stimuli included a watch, mirror, model of a beetle, and the
      experimenter's hand. However, when the marmosets viewed a threatening stimulus, a
      model resembling two rearing snakes, they displayed increased arousal (indicated
      by longer duration between monocular viewing events and increased incidence of
      aroused vocalisations) and the eye preferences shifted away from a preference for
      the right eye to either no preference or a left-eye preference. No relationship
      between eye preference and hand preference for holding food was found. Therefore,
      we suggest that eye preferences may reflect hemispheric specialisations for
      perceptual processing, according to the emotional valence of the stimulus.

PMID- 15513079
TI  - Speech lateralisation in callosal agenesis assessed by the dichotic fused words
      test.
AB  - Child patients with left-hemisphere damage (n = 2), with total callosal agenesis
      (n = 2), and with partial callosal agenesis or hypotrophy (n = 3) were submitted
      to dichotic verbal stimulation by the Fused Words Test. The controls were nine
      normal children, right-, left-, and mixed-handed. As expected, the left-injured
      patients presented a massive advantage of the ear contralateral to the intact
      hemisphere. Among the controls the right-handers showed a significant right-ear
      prevalence, whereas left-and mixed-handers exhibited rather inconsistent
      earasymmetries. The major finding of this study is the striking difference in
      perceptual asymmetry between partial and total acallosals. Based on the notion
      that the dichotic verbal asymmetry is an effect of the underlying functional
      asymmetry for language, these findings are interpreted as an indication that
      development of the unilateral speech control is influenced by the presence,
      during ontogenesis, of callosal connections.

PMID- 15513080
TI  - The effect of right and left hemispheric lesions on effortful and automatic
      memory tasks.
AB  - The effect of lateralised cerebral damage on two memory tasks-free recall of
      words and memory of their temporal order-was investigated under intentional,
      incidental, and ''true incidental'' learning conditions. Ten Right Brain Damaged
      patients (RBD), 10 Left Brain Damaged patients (LBD), as well as 15 age-matched
      and 15 younger control individuals, participated in this study. It was
      hypothesised that effortful and automatic memory processes involve predominantly
      the left and right cerebral hemispheres, respectively. Automaticity was defined
      either by the learning conditions (i.e. incidental-automatic and intentional
      effortful) or by the type of task (i.e. temporal-order-automatic and free-recall
      effortful) regardless of the learning conditions. In the free recall task the RBD
      group outperformed the LBD group under all learning conditions. In the temporal
      order task, the RBD group performed worse than normal controls under all learning
      conditions while the LBD group performed more poorly than matched controls in the
      intentional and incidental but not in the ''true incidental'' learning condition.
      The results are discussed in terms of the relationship between effortful and
      automatic memory processes and cerebral lateralisation.

PMID- 15513081
TI  - Handedness as a marker for drug hypersensitivity.
AB  - Several causal observations and a few recent studies suggest that left-handers
      may have greater reactivity to various drugs. A sample of 747 adults was surveyed
      to determine if they had had signs of hypersensitivity to commonly prescribed
      pharmaceutical drugs. Left-handers were significantly more likely to experience
      constipation, dizziness, and skin rashes, and were nearly three times more likely
      to experience other, miscellaneous, negative drug reactions. In addition left
      handers were nearly twice as likely to have experienced situations where their
      physician felt it necessary to reduce drug dosages because of unwanted side
      effects of medication. A second experiment using 840 adults indicated that a
      potential confound that would result if left-handers simply used more medical
      drugs in general, which would then give them more occasions on which reactions
      could occur, does not explain these results. Mechanisms that might account for
      these differences in drug sensitivity include differences in brain morphology,
      birth stress related neuropathy, and differences in immune system responses, all
      of which have been found to differ as a function of handedness.

PMID- 15513082
TI  - Haptic memory and handedness in 2-month-old infants.
AB  - This study examined the robustness of infant haptic memory, asymmetry between
      hands, and sex differences in haptic memory in infancy. A total of 96 2-month-old
      infants (half males, half females) were habituated haptically to an object with
      their right and their left hand, out of the field of view. Haptic memory was then
      tested under three conditions: after haptic interference, after a 30-second
      delay, or after no delay. The results show that haptic habituation occurred for
      both hands. The girls needed more time to habituate with their left hand than
      with their right hand, and they habituated more slowly than the boys did.
      Discrimination was also found in both hands and in both sexes. Haptic delayed
      recognition memory was only found in young boys mainly after a short delay and
      under certain conditions after interference. In young girls, recognition memory
      was found after interference only with the left hand. This result seemed to
      depend on the information processing speed. Thus, for memory performance, a sex
      difference was clearly observed. Moreover, the infants' left hand retained better
      information on object shape than did the right hand for both the sexes.
      Asymmetries in infancy are discussed in connection with the difference in brain
      maturation rate.

PMID- 15513084
TI  - Schizophrenia risk and handedness: a mixed picture.
AB  - Numerous previous studies have reported on handedness differences among
      schizophrenics, as well as in normal subjects who are high in ''schizotypal''
      traits, and hence putatively at risk for schizophrenia. Results have varied, but
      there is evidence of a shift away from dextrality, especially consistent among
      schizotypal individuals. Using both a conventional three-category and Annett's
      seven-category classification of handedness, we re-examined the question in 681
      general population subjects assessed for schizotypy. The three-category analysis
      confirmed previous findings of increased schizotypy in mixed-handers. However,
      the more fine-grained analysis showed that, although mild degrees of mixed
      handedness were indeed associated with increased schizotypy, this trend was
      reversed in the most mixed-handed subjects whose schizotypy scores did not differ
      significantly from right-handers. Independently of our work, this subgroup of
      mixed-handers are also reported to show superior intellectual function,
      especially on some spatial tasks. We concluded that previous studies of
      schizophrenia and schizotypy have failed to distinguish different reasons for
      shifts from dextrality. It is argued that the latter's association with
      schizophrenia might come about through exogenous, neurodevelopmental, influences,
      whereas some-possibly genetically basedforms of mixed handedness could reflect a
      variety of cerebral organisation that protects against, rather than enhances, the
      risk for mental disorder.

PMID- 15513085
TI  - Handedness in mental retardation.
AB  - Mentally retarded and age-matched normal controls with no history of parental
      sinistrality were examined for their handedness with the Waterloo Handedness
      Questionnaire (Singh & Bryden, 1994). Normal controls showed a clear rightward
      bias, with the effect being significantly higher for skilled as compared to
      unskilled hand items. Mentally retarded subjects showed mixed handedness with a
      nonsignificant difference in performance between skilled and unskilled hand
      items.

PMID- 15513086
TI  - Relation between language lateralisation and spatial ability in gay and straight
      women and men.
AB  - Delineating the relationship between language lateralisation and spatial ability
      remains an elusive goal. To explore the association of sexual orientation to the
      language lateralisation/spatial ability relationship, heterosexual (HT) women, HT
      men, lesbians, and gay men (20 per group) completed a divided-visual-field
      lexical-decision task to assess relative degrees of language lateralisation, as
      well as a Water Level Task (WLT) and two Mental Rotation (MR) Tasks designed to
      assess spatial ability. A significant cross-sex shift was revealed in the
      language lateralisation of gay men. Further, language lateralisation positively
      correlated with MR ability in HT men and tended to positively correlate with
      spatial perception in HT women. No significant associations were revealed in
      homosexual subjects. Different patterns of functional hemispheric asymmetry in
      homosexual and heterosexual individuals are discussed in relation to early
      neurobiological factors influencing the development of sexual orientation.

PMID- 15513087
TI  - Seasonal trends in the birth of sinistrals.
AB  - This study examined the proposition that hand preference may change with season
      of birth in a group of 523 students born in southern Australia. Hand preference
      and performance measures revealed a higher incidence of sinistrality or weak
      dextrality for individuals born in winter and autumn compared to summer and
      spring. These seasonal effects tended to be more pronounced for females compared
      to males. Similar seasonal patterns have been observed in the northern
      hemisphere. Previous research has accounted for seasonal changes in hand
      preference in terms of changes in the frequency of viral infections. It is
      proposed that seasonal variations in hand preference can also be accounted for by
      seasonal variations in hormone levels. Higher levels of testosterone in spring
      compared to autumn have been reported in females. Exposure to higher levels of
      testosterone during the first trimester of foetal development is thought to
      promote the development of the right hemisphere. Individuals born in winter would
      have been exposed to the high testosterone levels associated with spring during
      the first critical trimester of foetal brain development. The lack of seasonal
      effect observed for males may be related to endocrinological differences between
      the male and female foetus.

PMID- 15513088
TI  - Quantifying hand preference using a behavioural continuum.
AB  - Bishop, Ross, Daniels, and Bright (1996) proposed a novel approach to quantifying
      hand preference (QHP) using a single behavioural measure. The extent to which
      individuals used their dominant hand to reach across the midline to pick up cards
      discriminated subgroups of right-handers, similarly categorised by their scores
      on the Edinburgh Handedness Inventory. This study aimed to investigate whether
      (1) the QHP approach was able to differentiate subgroups within the left-handed
      as well as right-handed populations, (2) left-handers behave like mirror-image
      right-handers, and (3) if interacting with the environment in extrapersonal space
      is influenced by the level of fine motor skill demanded by the task. Results
      support the use of the QHP to discriminate subgroups of both left- and right
      handers, particularly when the task demands very fine motor skill or very little.
      Left-handers behaved as mirror-images of the right-handers except when performing
      the unskilled motor task in which they showed greater readiness to use the
      nonpreferred hand. These results suggest that interaction with the environment in
      extrapersonal space may be a key factor contributing to manual dominance and that
      the lateralisation of fine motor skill interacts with this attentional bias.

PMID- 15513089
TI  - Teat preference for suckling in common marmosets: relationship to side of being
      carried and hand preference.
AB  - Mother-infant interaction in common marmosets ( Callithrix jacchus jacchus ) was
      scored for the first 60 days post parturition. Teat preference was compared to
      hand preference for picking up and holding food over the same ages and at 18
      months. All infants, except one, exhibited strong preferences for one of the
      mother's teats. Preference for a teat was maintained when twins suckled
      separately as well as together. Infants suckled separately for a mean 42% of the
      time of all suckling bouts being observed. There was a significant correlation
      between teat preference and the side of being carried by the mother. This
      correlation was maintained despite the fact that the father also carried the
      infants. There was no significant relationship between teat preference and hand
      preference from 0 to 2 months or later life.

PMID- 15513090
TI  - Visual determinants of the leftward cradling bias: a preliminary report.
AB  - A dominant leftward cradling bias is typically found in women in non-feeding
      interactions with infants. The present study investigated Manning and
      Chamberlain's (1991) claim that the perception of an infant, or doll, in the left
      visual field was critical for the establishment of this cradling preference. A
      leftward bias, of similar magnitude to that shown in previous studies, was shown
      in a sample of undergraduate female students when their left eye was not
      occluded, and in imagery. Unexpectedly, the cradling bias was not significantly
      affected by left eye occlusion. Paradoxically, a group of males, who showed no
      clear lateral bias, were strongly affected by eye occlusion. A strong leftward
      cradling bias was also found in the blind. These data do not support the
      suggestion (Manning & Chamberlain, 1991) that visual information is a primary
      determinant of the leftward cradling bias.

PMID- 15513091
TI  - Left-footedness in peacocks: an emperor's tale.

PMID- 15513092
TI  - Footedness in peacocks: is the dominant foot the one raised first in climbing,
      and what, in any case, does the emperor's tale really mean?

PMID- 15513093
TI  - A reaching test reveals weak hand preference in specific language impairment and
      developmental co-ordination disorder.
AB  - A reaching test for quantifying hand preference (QHP task) was given to 7- to 11-
      year-old children with specific language impairment (SLI) or developmental
      coordination disorder (DCD). The performance of these clinical children was
      compared to both an age-matched and younger control group. The four groups did
      not differ in terms of preferred writing hand or preference on a handedness
      questionnaire. The QHP measure discriminated the clinical and younger control
      groups from the age-matched controls, but not from each other. Right-handed
      children with SLI, DCD, and the younger controls reached predominantly with the
      right hand to spatial positions located to the right of their body's midline and
      with the left hand to positions situated to its left. Right-handers in the age
      matched control group showed a significantly greater tendency to use their right
      hand to reach to all spatial positions. The increased tendency of the children
      with SLI to use the non-preferred hand was particularly striking because it was
      seen both in those with and without recognised motor difficulties. The QHP task
      appears to be a sensitive, but non-specific, indicator of developmental
      disorders.

PMID- 15513094
TI  - Something sinistral going on? Asymmetry in arm movement frequency.
AB  - In a test of the hypothesis that the dominant arm would be more active than the
      nondominant arm, 70 young adults (including 34 left-handers) wore instrumented
      motion recorders on both wrists for 48 hours. Participants' left arms made
      approximately 80 more movements per hour than did their right arms, which was
      unexpected. This mean difference reflected a generalised leftward shift in the
      distribution of the frequency of arm movements. Two-thirds of the individuals in
      the sample were characterised by a sinistral bias in arm movement frequencies.
      Degree of sinistral bias in arm movement frequency was unrelated to hand
      preference as measured by the Waterloo Inventory. Implications of this new
      asymmetry are discussed.

PMID- 15513095
TI  - Handedness, footedness, and language laterality: evidence from Wada testing.
AB  - A total of 37 candidates for temporal lobe resection for epilepsy completed the
      Lateral Dominance Examination, a self-report instrument that measures hand and
      foot preference. Questionnaire results were compared with speech dominance, which
      had been determined by Intracarotid Sodium Amytal Procedure. Footedness was as
      good as handedness as a predictor of language laterality.

PMID- 15513096
TI  - A crossover interaction between sex, sexual orientation, and handedness.
AB  - The distribution of handedness scores was analysed in 1414 heterosexual,
      bisexual, and homosexual men and women. Hand preference was assessed by a
      questionnaire that distinguishes consistently right-handed from partially or
      completely left-handed individuals, and sexual orientation was measured by the
      Kinsey scales. As expected from population-based studies, heterosexual men were,
      on average, more left-handed than heterosexual women. By contrast, gay men were
      more right-handed than lesbians or heterosexual men, and lesbians were more left
      handed than gay men or heterosexual women. This crossover interaction suggests
      that a common variable influences sex, sexual orientation, and hand preference.

PMID- 15513097
TI  - Hemispheric asymmetry for word naming: effects of frequency and regularity of
      pronunciation.
AB  - Observers named visually presented words as quickly as possible when the words
      were presented to the centre of a viewing screen (Experiments 1, 5, and 6) or
      were flashed to either the left visual field/right hemisphere (LVF/RH) or right
      visual field/left hemisphere (RVF/LH) on each trial (Experiments, 2, 3, and 4).
      Words varied in frequency of occurrence in the language and in regularity of
      pronunciation. On lateralised trials, there was a RVF/LH advantage for both error
      rate and reaction time, with this hemispheric asymmetry for word naming being
      independent of both frequency and regularity. The RVF/LH advantage was also
      independent of whether the letters within a word were arranged horizontally or
      vertically. Error rates and reaction times were lower for high-than for low
      frequency words and lower for words with a regular pronunciation than for
      exception words. In addition, on centre trials the effects of regularity were
      larger for low-frequency words than for high-frequency words. However, when words
      were presented in the visual periphery, the effects of regularity were of the
      same magnitude for high-and low-frequency words. In view of the theoretical
      importance of the Frequency by Regularity interaction, this latter result
      suggests that word processing is qualitatively different in the visual periphery
      than in the centre of vision; indicating that perceptual asymmetries in a typical
      visual half-field experiment may be limited in what they can tell us about the
      relative contributions of the two hemispheres to processing words in the centre
      of vision.

PMID- 15513100
TI  - Speculations about the nature and inheritance of biological asymmetries.

PMID- 15513101
TI  - The relation between hand preference and hand performance: what you get depends
      on what you measure.
AB  - In the present investigation, we addressed the relation between manual preference
      and performance. A total of 52 right-handers and 48 left-handers were tested for
      manual proficiency and preferences using a range of tasks. Self-professed right
      and left-handers showed greater preference for, and superior performance with,
      the preferred hand. Left-handers use their nonpreferred hand more often and in
      some instances are more skilled with it than right-handers. There was a subgroup
      of persons with mixed handedness, who identified themselves as left-handed, wrote
      with the left hand, and were more skilled with the left hand on dot-filling, but
      who were otherwise right-handed. Overall, the data indicated that a complete
      description of handedness will only be provided by careful consideration of the
      nature of the preference and performance measures one uses.

PMID- 15513102
TI  - Spatial task demands affect the extent of manual asymmetries.
AB  - The degree of hand preference and the magnitude of hand differences in
      performance are thought to relate to skill level. The purpose of the experiments
      discussed here was to examine the effect of skill as reflected in the spatial
      precision demands of a movement, on the extent of manual asymmetries. Experiment
      1 utilised the Annett pegboard, and manipulated spatial precision by varying peg
      diameter. The second experiment utilised the Grooved pegboard, and manipulated
      spatial precision by altering the size of the target hole. Analyses revealed that
      movement time increased as a function of the increased spatial precision demands.
      Although the preferred hand was always faster, the magnitude of this advantage
      was only affected in Experiment 2, in which the manipulation of spatial precision
      was maximal. The implications of these findings for the skill interpretation of
      handedness are discussed.

PMID- 15513103
TI  - Sex and hemispheric differences for rapid auditory processing in normal adults.
AB  - Previous research suggests that left hemisphere specialisation for processing
      speech may specifically depend on rate-specific parameters, with rapidly
      successive or faster changing acoustic stimuli (e.g. stop consonant-vowel
      syllables) processed preferentially by the left hemisphere. The current study
      further investigates the involvement of the left hemisphere in processing rapidly
      changing auditory information, and examines the effects of sex on the
      organisation of this function. Twenty subjects participated in an auditory
      discrimination task involving the target identification of a two-tone sequence
      presented to one ear, paired with white noise to the contralateral ear. Analyses
      demonstrated a right ear advantage for males only at the shorter interstimulus
      interval durations (mean = 20 msec) whereas no ear advantage was observed for
      women. These results suggest that the male brain is more lateralised for the
      processing of rapidly presented auditory tones, specifically at shorter stimulus
      durations.

PMID- 15513104
TI  - Sex differences in material-specific cognitive functions related to language
      dominance: an intracarotid amobarbital study in left temporal lobe epilepsy.
AB  - Population-based studies of material-specific cognitive functions yield evidence
      of sex differences: women are superior on verbal tasks whereas men are superior
      on figural and visuo-spatial tasks. Although there is still no direct evidence,
      these sex differences have been assumed to be related to a different cerebral
      organisation of language and nonlanguage functions, i.e. language in women is
      suggested to be more bilaterally organised than in men. We investigated this
      issue with respect to verbal/nonverbal memory functions in 42 men and 43 women
      with left temporal lobe epilepsies who all underwent intracarotid amobarbital
      testing for language dominance. The results indicate that atypical language
      dominance is not significantly more frequent in women than in men (44% vs 33%).
      Atypical dominance was related to an onset of epilepsy before puberty and
      appeared to be a consequence of the left hemisphere pathology rather than being
      naturally predisposed. Furthermore, women indeed showed the expected advantage
      with respect to verbal memory, and men showed an advantage in figural memory.
      With consideration of language dominance, however, the sex difference in verbal
      memory was observed particularly with atypical dominance, whereas the sex
      difference in figural memory was observed with left dominance.

PMID- 15513105
TI  - Left hand preferences in capuchins (Cebus apella): role of spatial demands in
      manual activity.
AB  - Sixteen capuchins (Cebus apella) participated in four tasks that differed in
      their exploration demands and availability of visual cues. The two explorative
      tasks required the monkeys to discover sunflower seeds hidden in crevices in
      objects of various shapes, with vision (Haptic-Visual task) or without vision
      (Haptic task). Two other tasks required the capuchins to grasp sunflower seeds
      directly on a flat support, with vision (Visual reaching) or without vision
      (Tactual reaching). The presence or absence of exploration demands had a
      significant effect on the direction of hand preferences. The group displayed
      greater left hand preferences for the Haptic and Haptic-Visual tasks than for the
      two reaching tasks. The strength of manual preferences did not differ
      significantly among the four tasks. These findings suggest that the manipulo
      spatial demands of a task are of particular importance for the expression of left
      hand bias in a population of capuchins. It is argued that left hand preferences
      for the haptic tasks may reflect a right hemisphere specialisation to integrate
      the spatial and motor components of action.

PMID- 15513106
TI  - Manual laterality in anvil use: wild chimpanzees cracking Strychnos fruits.
AB  - Wild chimpanzees (Pan troglodytes schweinfurthii) at Gombe National Park,
      Tanzania, smash open the hard-shelled fruits of Strychnos spp. on anvils of stone
      or woody vegetation. In this food-processing task, most of the apes show
      exclusive use of one hand or the other, that is, strong individual hand
      preferences. Such extreme laterality of manual functioning corresponds to Level 3
      on a five-level descriptive model of lateralisation that appears to reflect the
      increasingly skillful demands of object manipulation. There is precise congruence
      in laterality between anvil use and another subsistence task involving elementary
      technology-termite fishing-in almost all cases.

PMID- 15513107
TI  - Footedness in binocular and monocular chicks.
AB  - The first foot used during bouts of ground scratching in 16-day-old chicks
      searching for food in the floor of an arena covered with sawdust was recorded in
      animals with normal binocular vision and in animals with an eye temporarily
      occluded by an eye-patch. Binocular chicks showed a significant right foot bias,
      whereas monocular chicks tended to use the foot contralateral to the eye in use.
      Data for monocular chicks thus suggest that the activated hemisphere
      (contralateral to the eye in use) is the one that takes control of posture,
      leaving to the other hemisphere reflex-like responses associated with ground
      scratching or body wiping. It is argued that footedness in chicks might have
      arisen from the limb that is used to maintain postural and positional control,
      rather than from the limb that is used during motor activities.

PMID- 15513108
TI  - Orthographic and phonological facilitation from unattended words: evidence for
      bilateral processing.
AB  - This study investigated hemisphere differences in sensitivity to orthographic and
      phonological similarity using a task that did not require deliberate
      metalinguistic comparisons between words. Two experiments investigated the
      influence of an unattended distractor item on the pronunciation of target words
      in the right visual field (RVF) and left visual field (LVF) in neurologically
      intact persons. Word and pseudoword distractors that were both orthographically
      and phonologically similar to the target word produced equivalent facilitation
      across visual fields (Exp. 1). When orthographic and phonological influences were
      separated in Exp. 2, each dimension produced reliable facilitation, and to the
      same extent in each visual field. These results, and others in the literature,
      are difficult to reconcile with the view that the intact right hemisphere is
      completely unable to access phonology from print. If subsequent research confirms
      these findings, it would suggest that passive activation of phonology in reading
      can be dissociated from articulatory mechanisms, and that left hemisphere
      superiority in some phonological judgements may depend more on the availability
      of articulatory rehearsal than on privileged access to phonological codes.

PMID- 15513109
TI  - Task and stimulus demands influence letter-case-specific priming in the right
      cerebral hemisphere.
AB  - A greater tendency to complete single-completion word stems (e.g. "BEY") to form
      previously read whole words (e.g. "BEYOND") was found when test stems were
      presented in the same letter case as their previously encoded words, compared
      with the different letter case, but only when stems were presented directly to
      the right hemisphere (i.e. in the left visual field) and not when they were
      presented directly to the left hemisphere (i.e. in the right visual field). This
      finding with single-completion stems was robust (i.e. observed for both lowercase
      and uppercase stems) when the initial encoding task was perceptually demanding,
      but it was test-case dependent (i.e. observed for uppercase but not lowercase
      stems) when the initial encoding task was not perceptually demanding. Results and
      theory help to explain why letter-case-specific priming in right-hemisphere test
      presentations is typically test-case dependent when priming is measured using
      perceptual identification at test, but is consistently robust when priming is
      measured using multiple-completion word stems (e.g."BEA") at test. Demands from
      both the stimuli and tasks affect the relative contributions of abstract and
      specific subsystems to the processing of visual forms.

PMID- 15513110
TI  - Hemisphere differences in accessing lexical knowledge of Chinese characters.
AB  - The lateralisation of lexical knowledge of Chinese characters is investigated in
      this study. Three experiments were conducted in which stimuli were presented
      unilaterally to a visual field for recognition tests. The orthographic similarity
      of two alternative items for choice in Experiment 1 was manipulated, and the
      results showed an LVF advantage effect for legal characters in the visually
      similar condition and a more prominent LVF than RVF character-superiority effect.
      The phonological similarity of two alternative items for choice was manipulated
      in Experiment 2. The results showed a prominent RVF advantage effect and a
      significant phonological similarity effect in the RVF. In Experiment 3, the
      semantic similarity was manipulated, and the semantic similarity effect was
      observed in the RVF. These results suggest hemisphere asymmetries in accessing
      lexical knowledge of Chinese characters.

PMID- 15513111
TI  - Eye dominance in families predicted by the right shift theory.
AB  - The proportions of nonright-eyed children in families with 0, 1, or 2 nonright
      eyed parents resemble those for nonright-handed children in the families of
      nonrighthanded parents. Both sets of proportions are consistent with the Annett
      right shift genetic model of human asymmetry. The suggestion that findings for
      eyedness in families are incompatible with genetic theories of handedness (Reiss
      & Reiss, 1997) is correct for the McManus theory but false for the Annett theory.

PMID- 15513112
TI  - Eye-dominance, writing hand, and throwing hand.
AB  - Handedness and eye-dominance are undoubtedly associated statistically, although a
      previous meta-analysis has found that the precise relationship is difficult to
      explain, with about 35% of right-handers and 57% of left-handers being left eye
      dominant. Of particular difficulty to genetic or other models is that the
      proportions are distributed asymmetrically around 50%. The present study asked
      whether this complicated pattern of association occurred because, following
      Peters, it is necessary to divide right-and left-handers into consistent handers
      (who write and throw with the same hand) and inconsistent handers (who write and
      throw with opposite hands). In an analysis of 10,635 subjects from questionnaire
      studies, 28.8% of left-handers and 1.6% of right-handers by writing were
      inconsistent for throwing. Our results also showed that writing hand and throwing
      hand both relate independently to eyedness, that throwing hand is somewhat more
      strongly associated with eyedness, and that the awkward asymmetry around 50% is
      now removed, 24.2% of consistent right-handers being left eye dominant compared
      with 72.3% of consistent left-handers, and 55.4% of inconsistent right-handers
      compared with 47.0% of inconsistent left-handers. We conclude that eyedness is
      phenotypically secondary to writing and throwing handedness. In our discussion we
      note that eyedness runs in families, we present new data suggesting that writing
      hand and throwing hand are co-inherited, and we argue that further data are now
      required to model properly the associations of writing hand, throwing hand, and
      eyedness, as well as probably also footedness and language dominance.

PMID- 15513113
TI  - Of geminates and gemellology.

PMID- 15513114
TI  - Twinning and embryonic left-right asymmetry.

PMID- 15513115
TI  - Symmetry and asymmetry in the development of inner organs in parabiotic twins of
      amphibians (Urodela).
AB  - Newt embryos of different developmental stages were combined to parabiotic twins
      in different positions. The exterior appearance and the symmetry relations,
      particularly of the internal organs (intestinal tract, heart, nuclei habenulae,
      and vitelline vein) were studied. Experimentally caused organ inversions allowed
      conclusions with respect to organ asymmetry and unilateral dominance. There was
      no direct correlation between appearance and symmetry of the exterior and the
      internal organs. All internal organs showed a continuous transition between
      normal and ideally inverse situs. The concordance of the organ situs differs
      greatly. The "left-hand side" or "right-hand side" dominance is not uniform. It
      depends on the type of fusion, i.e. the relative position of the parabiotic
      twins, and is often specific for a given organ. In some cases a non-genetic
      "symmetrisation factor" appears to be strongly active, depending on the fusion
      type and resulting in a dominant transindividual organ mirror image symmetry in
      the parabiotic twins. The older twin generally dominates the processes of
      determination and induction. The "symmetrisation factor" also acts on members of
      different families, i.e. genetically completely heterogeneous parabiotic twins.
      The development of organ asymmetry appears to be a process with several phases.

PMID- 15513116
TI  - Handedness in the NAS/NRC twin study.
AB  - In 1985, a hand preference survey was completed by 973 dizygotic and 1158
      monozygotic male twin pairs, all veterans of World War II. This is the largest
      single twin study of handedness on record. As in state-of-the-art animal
      research, the laterality criterion was sensitive to both direction and
      consistency (degree, strong or weak) of handedness. Significant pairwise
      concordance was shown for the total group, and for consistency and directional
      factors separately. However, no zygosity differences were demonstrated.

PMID- 15513117
TI  - Handedness in twins: a meta-analysis.
AB  - In the largest meta-analysis of twins and singletons conducted to date we have
      found a higher incidence of left-handedness in twins compared to singletons. Our
      analysis revealed no difference in the frequency of left-handedness among
      monozygotic versus dizygotic twins. However, identical twins were more likely to
      be concordant for hand preference than non-identical twins, which is consistent
      with a genetic model of handedness. Prior analyses have not revealed these
      findings consistently, and this has led to a number of conflicting models of
      handedness.

PMID- 15513118
TI  - Laterality of hand, foot, eye, and ear in twins.
AB  - Information on handedness, footedness, eyedness, and earedness was collected from
      33 monozygotic (MZ) twin pairs and 67 dizygotic (DZ) twin pairs. The incidence of
      nonright-sidedness in the twins is not higher than that reported in the
      literature for singletons. Similar results are found for the other lateralities.
      The results of assessing handedness with preference tests do not differ from
      those carried out with performance tests. There are no differences in incidence
      of nonright-sidedness between MZ and DZ twins. The concordance of lateralities is
      similar in MZ and DZ twins. The proportions of Right-Right, Right-Nonright, and
      Nonright-Nonright pairs in both groups of twins show a binomial distribution. The
      present results do not confirm a genetic hypothesis of determination of sidedness
      in humans and are comparable with the results obtained by other twin studies.

PMID- 15513119
TI  - A twin study of individual differences in perceptual asymmetry.
AB  - Individual differences in perceptual asymmetry have been associated with
      individual differences in cognitive abilities, personality characteristics, and
      psychiatric symptoms, for which between-person variation appears to be
      genetically influenced. Perceptual asymmetry scores are also associated with
      direction of handedness, for which between-person variation does not appear to be
      genetically influenced. To assess whether between-person variation of perceptual
      asymmetry scores is genetically influenced, we examined asymmetry on a freevision
      task of face processing, the Chimeric Faces Task (CFT), in a sample of 31
      monozygotic (MZ) and 20 same-sex dizygotic (DZ) twin pairs. MZ and DZ within twin
      pair resemblances were compared to assess genetic and familial influences on
      asymmetric hemispheric function. We found that twins within a pair were no more
      likely to resemble each other than were unrelated individuals. The results
      suggest that the between-person variation in CFT perceptual asymmetry is not
      influenced by genes or shared environment.

PMID- 15513120
TI  - Hemisphere specialisation and categorical spatial relations representations.
AB  - Hemisphere specialisation in two- and three-dimensional categorical spatial
      relations tasks was investigated using normal adult subjects. In Experiment 1,
      subjects were asked to indicate the rightmost (or leftmost) card in stimuli
      consisting of three overlapping cards as quickly and as accurately as possible.
      The results showed no significant visual field difference in either response
      times or error rates. In Experiment 2, stimuli identical to those of Experiment 1
      were used and subjects were asked to indicate the card most to the front or the
      one most to the back. The error rates showed a strong tendency towards a left
      visual field advantage in accuracy while no visual field difference was shown in
      response times. Based on these findings, relations between the hemisphere
      specialisation and categorical spatial relations encoding subsystems in Kosslyn's
      (1987) model of visual information processing are discussed.

PMID- 15513121
TI  - Midline-crossing inhibition: an indicator of developmental delay.
AB  - In normal development midline crossing integration is usually attained by eight
      or nine years of age. The inability to attain this developmental milestone is
      called midline crossing inhibition (MCI). A new method to detect MCI was used to
      examine the presence of MCI in a group of subjects with mental retardation.
      Seventeen subjects with mental retardation and an equal number of non-disabled
      peers participated in the study. Choice response time measurements consisting of
      reaction time and movement time were the dependent variables. These variables
      were recorded when subjects executed ipsilateral, midline and contralateral
      movements with each leg. Analysis of data revealed for both dependent variables
      significant differences between the two groups of subjects. Only the group with
      mental retardation exhibited contralateral times that were significantly slower
      than ipsilateral times. Midline crossing inhibition was evident with these
      developmentally delayed subjects. This new method shows promise for assessing
      developmental and neurological anomalies.

PMID- 15513122
TI  - Quantitative assessment of five behavioural laterality measures: distributions of
      scores and intercorrelations among right-handers.
AB  - Five behavioural laterality measures (degree of right-handedness, ear dominance,
      ocular dominance, line bisection performance, and lateral preference as assessed
      by preferred direction of conjugate lateral eye movements) were analysed in 1171
      right-handers by merging data from 15 different samples. All laterality aspects
      were assessed quantitatively by using well controlled performance measures
      instead of questionnaires. The distributions and intercorrelations of the
      measures as well as their test-retest reliabilities were examined. Results show
      moderately high reliabilities for all measures, and clearly demonstrate
      considerable variability among dextrals in the direction and magnitude of the
      obtained behavioural laterality measures. Most importantly, independence of the
      different measures questions some common assumptions in laterality research. It
      seems unlikely, for instance, that handedness and other aspects of laterality may
      be a product of one single underlying mechanism of brain lateralisation.

PMID- 15513123
TI  - Handedness effects on playing a reversed or normal keyboard.
AB  - A group of left-handers, approaching the piano for the first time, showed better
      performance in playing a reversed keyboard (where the pitch decreased from left
      to right) than a normal keyboard. By testing a separate group of "experienced"
      left-handers, it was also found that this observed preference that naive left
      handers had for the reversed keyboard can disappear with a few years of practice
      on a normal keyboard. The initial preference for the reversed keyboard shown by
      left-handers appeared to be specific for this handedness group, as groups of
      right-handers, regardless of their level of experience with the piano, performed
      better with the regular keyboard. Finally, based on these results it was
      hypothesised that left-handers would encounter considerable frustration in
      learning the "right-handed" piano. However, an informal demographic study of
      piano students enrolling at a school of music did not reveal a substantially low
      prevalence of left-handed pianists.

PMID- 15513124
TI  - Incremental improvement of dichotic left ear accuracy and toe gnosis between 9
      and 10 years of age: implications for maturation of a portion of the corpus
      callosum and of the sense of self.
AB  - Analyses of the data from 212 boys and girls, aged 7-14 years, demonstrated a
      relatively abrupt and permanent decrease in the numbers of errors for dichotic
      (left ear) word listening and for toe gnosis after the ninth year. This pattern
      was not observed for right ear errors, finger gnosis, or indices of finger and
      foot agility. The results are compatible with the hypothesis that the final
      differentiation of the paracentral lobules and adjacent corpus callosum by the
      most distal portions of the Anterior Cerebral Artery occurs around 9 or 10 years
      of age. Implications for the development of the sense of self, enhanced
      apprehension, and "the sense of a presence" are discussed.

PMID- 15513126
TI  - Hemispheric asymmetries in activation and integration of categorical information.
AB  - Hemispheric asymmetries in activation and integration of semantic information
      were studied in the normal brain. In Experiment 1, categorically related primes
      and targets (HAND-NOSE) were presented to the left visual field (LVF) or to the
      right visual field (RVF) in a primed lexical decision task. The ratio of nonword
      targets in relation to all unrelated targets in the stimulus lists was
      manipulated. It was assumed that at the low nonword ratio the priming effects
      would primarily tap automatic semantic processing. At the higher ratio, priming
      would be generated predominantly by postlexical meaning integration or semantic
      matching. The results revealed automatic priming in the RVF/left hemisphere and
      postlexical priming in the LVF/right hemisphere. Experiment 2 measured automatic
      categorical activation with the lower nonword ratio and by presenting primes at
      the centre of the field. Bilateral priming was observed. It is suggested that the
      left hemisphere automatically activates categorically related word meanings in
      both hemispheres. The right hemisphere contributes by maintaining the meanings
      active and by retrospectively integrating them to the context.

PMID- 15513127
TI  - Inferring the nature of semantic processes by varying priming procedure: a reply
      to Koivisto and Laine.

PMID- 15513128
TI  - What is right and what is left in semantic processing: a reply to Chiarello.

PMID- 15513129
TI  - Semantic category and rhyming processing in the left and right cerebral
      hemisphere.
AB  - In this study, the question of hemispheric abilities in processing explicit
      semantic and phonological information was addressed by measuring response
      latencies and performances in two judgement tasks. In the semantic task, word
      pairs were sequentially presented to the left or right visual field and subjects
      were asked to judge whether these words were categorically related or not. In the
      phonological task, the same subjects were asked to decide whether pairs of
      orthographically dissimilar words rhymed or not. Statistical analysis showed that
      reaction times (RT) were significantly shorter in both tasks when words were
      presented to the right visual field. Furthermore, in the semantic task, faster
      responses were observed in both visual fields when the words were related than
      when they were unrelated. This response facilitation tended to be stronger when
      words were presented to the left visual field. This result is in accordance with
      other results obtained by lexical decision studies showing that priming in the
      right hemisphere is due to controlled processing. By contrast, RT differences
      between rhyming and non-rhyming word pairs in the phonological task did not reach
      significance. This supports previous findings showing that phonological
      facilitation cannot occur when orthographic and phonological indices are in
      conflict.

PMID- 15513130
TI  - Somatoperceptual asymmetry for cognitive stimuli: support from experimental and
      clinical observations.
AB  - Two studies, one experimental with intact-brain subjects (Study I), and one
      clinical with left or right hemisphere-damaged and non-neurological general
      medical patients (Study II), were conducted to examine somatolateral asymmetry in
      the recognition of verbal (letter) and visuospatial (nonsense shapes) stimuli.
      Blindfolded subjects were required to explore two stimuli dichhaptically, and
      were instructed to haptically identify the target stimulus in a set of test
      stimuli. The findings of Study I indicated that fewer trials were required to
      recognise nonsense shapes when they were presented to the left hand, whereas
      fewer trials were required for letters when they were presented to the right
      hand. The findings of Study II indicated that performance of the hand ipsilateral
      to the damaged left hemisphere was better for nonsense shapes than for letters,
      and performance of the hand ipsilateral to the damaged right hemisphere was
      better for letters than for nonsense shapes.

PMID- 15513131
TI  - Foot preference changes through adulthood.
AB  - Developmental observations in foot laterality suggest increasing right-footedness
      from early childhood to young adult years, with few reports on behaviour beyond
      this time frame. This investigation confirmed recent suggestions by Porac (1996)
      of a continuation of this trend into middle and older adulthood, along with
      significant decreases in mixed-and left-foot preferences. Trends towards
      increasing right-footedness are linked to hemispheric heterochrony (right
      hemisphere ageing) and the right-sided world phenomenon.

PMID- 15513132
TI  - Serum levels of female sex hormones in left-handed and right-handed menopausal
      women.
AB  - The study covered 25 left-handed and 27 right-handed clinically healthy females
      aged between 47 and 55 years during normal menopause. It was carried out in the
      third year from the beginning of amenorrhoea. The levels of the follicle
      stimulating hormone, luteinising hormone, proclactin, estradiol, and progesterone
      were determined by means of enzyme-immunological methods with IMX (Abbott, USA)
      and Serozyme I (Biochem Immunosystem Diagnostica, USA) apparatuses. It was
      established that in left-handed women the serum concentrations both of the
      follicle-stimulating hormone and luteinising hormone were significantly higher (P
      <.001), and those of prolactin, estradiol, and progesterone much lower (P <.001),
      as compared to the right-handed women.

PMID- 15513133
TI  - Individual differences in cognitive performance due to right hemisphere arousal.
AB  - The purpose of this study was to investigate the relationship between individual
      differences in cognition and asymmetric patterns of cortical arousal in normal
      right-handed adults. Leftward asymmetry on a chimeric faces task was correlated
      with the ability to recognise faces and facial expression, and certain aspects of
      social skill. The correlation with face and emotional expression recognition was
      significant only for subjects who reported using a non-verbal strategy. These
      results further support the role of the right hemisphere in various aspects of
      social cognition, but also point to the need to consider individual differences
      in strategies employed during task performance.

PMID- 15513135
TI  - Developmental instability and right shift theory hypotheses concerning correlates
      of familial sinistrality: negative findings.
AB  - Both the right shift (Annett, 1985) and developmental instability (Yeo &
      Gangestad, 1993) theories of handedness predict that familial sinistrality (FS)
      should relate to hand skill asymmetries (HSA) on peg-moving tasks. Annett also
      hypothesises that both HSA and a procedure she derived for classifying
      individuals according to the pattern of their hand preferences for different
      manual activities can index the genotypes posited in her theory, i.e. she
      believes these variables are highly correlated. These hypotheses were tested in a
      sample of 280 dextral college students. Results failed to support the finding of
      Gangestad and Yeo (1994) that subjects showing greater hand skill asymmetry
      deviations from typical asymmetry had a greater probability of having a left
      handed parent. There was also no support for Annett's finding that greater
      dextrality, as defined by her hand preference classification system, was
      negatively associated with familial sinistrality. Additionally, the relationship
      between HSA and Annett's hand preference classes was found to be exceedingly
      weak, contrary to Annett's theorising. These and other failures to find highly
      replicable differences between FS- and FS+ dextrals cast doubt on the validity of
      genetic or partial-genetic theories of handedness that posit a ''penetrance'' of
      a recessive non-dextrality-favouring gene that causes presumed dextral
      heterozygotic persons to differ from presumed homozygotic dominant persons in
      cognitive or manual skills.

PMID- 15513136
TI  - Family size, miscarriage-proneness, and handedness: tests of hypotheses of the
      developmental instability theory of handedness.
AB  - The handedness theory of Yeo and Gangestad (1993) posits that moderate right
      handedness is the modal manifestation of genetic handedness and that
      ''developmental instability'' produces deviations from modal handedness. It is
      also suggested (1) that sinistral parents may produce fewer offspring than do
      dextral parents; and (2) that sinistral mothers may be more prone to miscarriages
      than are dextral mothers. In line with these hypotheses, Gangestad et al. (1996)
      reported that a human leukocyte antigen (B8) was related to both left-handedness
      and to reduced offspring number in their study. They also found that left
      handedness was related to the human leukocyte antigen DR3, and Yeo and Gangestad
      (1998) noted that this antigen has been found by Christiansen et al. (1996) to be
      associated with an increased risk of spontaneous abortion in women. We assessed
      the first hypothesis through a study of the family sizes of 2083 families with
      two right-handed parents and 502 families having one or more left-handed parents;
      we assessed the second hypothesis from miscarriage history data supplied by 300
      dextral and 52 sinistral mothers. Results supported the developmental instability
      theory with respect to the hypothesis regarding family size, but not with respect
      to the hypothesis regarding miscarriage-proneness.

PMID- 15513137
TI  - The 2nd:4th digit ratio and asymmetry of hand performance in Jamaican children.
AB  - Testosterone, particularly prenatal testosterone, has been implicated in the
      aetiology of many extragenital sexually dimorphic traits. It is difficult to test
      directly for the effect of prenatal testosterone in humans. However, Manning,
      Scutt, Wilson, and Lewis-Jones (1998b) have recently shown that the ratio of the
      length of the 2nd and 4th digits (2D:4D) in right hands negatively predicts
      testosterone levels in men. As digit ratios are fixed in utero it may be that the
      2D:4D ratio is associated with many prenatally determined sexually dimorphic
      traits. We tested this for one case by examining the relationship between
      lateralised hand performance (LHP), as measured by an Annett peg board, and 2D:4D
      ratio in rural Jamaican children. 2D:4D ratio was measured from photocopies and X
      rays of hands. A low 2D:4D ratio in the right hand of boys and girls
      (photocopies) and the right hand of boys only (X rays) was associated with a
      reduction in rightward performance asymmetry. In both samples the difference in
      2D:4D ratio between the hands (2D:4D left hand-2D:4D right hand) showed the
      strongest relationship with LHP i.e. high ratio in the left and low in the right
      correlated with a tendency towards a fast performance with the left hand. It is
      suggested that the 2D:4D ratio may be associated with the expression of other
      sexually dimorphic behavioural traits.

PMID- 15513138
TI  - Post-lesion lateralisation shifts in a computational model of single-word
      reading.
AB  - The mechanisms underlying lateralisation of language are incompletely understood.
      Existing data is inconclusive, for example, in determining which underlying
      asymmetries in hemispheric anatomy/physiology lead to lateralisation, the precise
      role of interhemispheric connections in this process, and exactly how and why
      lateralisation can shift following focal brain damage. Although these issues will
      ultimately be settled by experimentation, it is likely that computational
      modelling can be used to suggest, focus, and even interpret such empirical work.
      We have recently studied the emergence of lateralisation in an artificial neural
      network model having paired cerebral hemispheric regions, as the model learned to
      generate the correct pronunciation for simple words. In this paper we extend this
      previous work by examining the immediate and longer-term changes in
      lateralisation that occur following simulated acute hemispheric lesions. Among
      other things, the results demonstrate that the extent to which the non-lesioned
      model hemispheric region contributes to recovery is a function of lesion size,
      prelesion lateralisation, and assumptions about the excitatory/inhibitory
      influences of the corpus callosum. The relevance of these results to the
      currently controversial suggestion that language lateralisation shifts following
      focal damage to language areas, and that the unlesioned hemisphere contributes to
      recovery from stroke-induced aphasia in adults, is discussed.

PMID- 15513139
TI  - Stages of functional processing and the bihemispheric recognition of Japanese
      Kana script.
AB  - Two experiments were carried out in order to examine the effects of functional
      steps on the benefits of interhemispheric integration. The purpose of Experiment
      1 was to investigate the validity of the Banich (1995a) model, where the benefits
      of interhemispheric processing increase as the task involves more functional
      steps. The 16 right-handed subjects were given two types of Hiragana-Katakana
      script matching tasks. One was the Name Identity (NI) task, and the other was the
      vowel matching (VM) task, which involved more functional steps compared to the NI
      task. The VM task required subjects to make a decision whether or not a pair of
      Katakana-Hiragana scripts had a common vowel. In both tasks, a pair of Kana
      scripts (Katakana-Hiragana scripts) was tachistoscopically presented in the
      unilateral visual fields or the bilateral visual fields, where each letter was
      presented in each visual field. A bilateral visual fields advantage (BFA) was
      found in both tasks, and the size of this did not differ between the tasks,
      suggesting that these findings did not support the Banich model. The purpose of
      Experiment 2 was to examine the effects of imbalanced processing load between the
      hemispheres on the benefits of interhemispheric integration. In order to
      manipulate the balance of processing load across the hemispheres, the revised
      vowel matching (r-VM) task was developed by amending the VM task. The r-VM task
      was the same as the VM task in Experiment 1, except that a script that has only
      vowel sound was presented as a counterpart of a pair of Kana scripts. The 24
      right-handed subjects were given the r-VM and NI tasks. The results showed that
      although a BFA showed up in the NI task, it did not in the r-VM task. These
      results suggested that the balance of processing load between hemispheres would
      have an influence on the bilateral hemispheric processing.

PMID- 15513140
TI  - Characteristics of the bimanual deficit using grip strength.
AB  - Grip strength was used to evaluate bimanual functioning and the bimanual deficit
      as a measure of the relationship between the hands and the hemispheres.
      Participants were 174 right-handed individuals. Experiment 1 measured maximal,
      unimanual, and bimanual grips. There were two bimanual, simultaneous grip
      conditions: (1) symmetrical (hands perform the same grip) and (2) asymmetrical
      (different grips for each hand). Decrements were equivalent for preferred and
      nonpreferred hands and were similar for males and females. Experiment 2 consisted
      of three variations of the bimanual, asymmetrical grip condition used in
      Experiment 1. Emphasis was imposed on a single hand via a performance criterion
      and feedback. Results indicated that emphasis imposed on either hand produced a
      strength increment compared to that hand's baseline, but did not affect the
      concurrently performing hand. Results suggest that the bimanual coordination is
      governed at a non-lateralised or inter-hemispheric level for both males and
      females.

PMID- 15513142
TI  - Handedness in past human populations: skeletal markers.
AB  - Although it is generally believed that right-handedness has predominated in all
      human populations since at least the appearance of Homo sapiens sapiens, the
      evidence has rarely been studied in its entirety. This paper contains a review of
      the principal skeletal indicators of handedness (cranial and post-cranial), and
      an introduction to their use to estimate the prevalence of left and right
      handedness in the past. The role of such reviews is to enable us to assess the
      testability of genetic models of human handedness and of its evolution, using
      anthropological and archaeological data.

PMID- 15513143
TI  - Hand skill and hand preference in blind and sighted children.
AB  - Congenitally blind and sighted blindfold children between the ages of 6 and 15
      years were compared with each other for hand preferences and hand ability. All
      the children performed a 20-item hand preference test and every child performed
      three hand ability tasks: a sorting task, a finger dexterity task, and the
      Minnesota rate of manipulation task, each separately with the left and the right
      hand. Results indicated no differences between the hand preferences of the two
      groups. The sighted children were faster than the blind children on some of the
      hand ability tasks. There were no differences between the left and right hands
      for any of the tasks for either group. Results indicate an equipotentiality
      between the hands and suggest the possibility of training both hands during
      development on tasks that require tactile ability.

PMID- 15513144
TI  - Lateralisation of perceptual processing of pro- and anti-social emotions
      displayed in chimeric faces.
AB  - Previous studies using a restricted range of split field chimeric faces suggest
      that the processing of facial emotional expressions is a highly lateralised
      phenomenon. Two theories have emerged with regard to the role the two cerebral
      hemispheres play in this processing. The "right hemisphere" hypothesis (e.g.
      Borod, Koff, Lorch, & Nicholas, 1988) suggests that the right hemisphere plays a
      prominent role in the processing of both positive and negative facial
      expressions. In contrast, the "valence hypothesis" (e.g. Reuter-Lorenz &
      Davidson, 1981) proposes that, while the right hemisphere plays the major role in
      processing negative emotions, the left hemisphere has a special role for positive
      emotions. Using all six of the human "universal facial expressions" (Ekman
      &Friesen, 1971) we present evidence that, superimposed onto a left visual field
      advantage (right hemisphere specialisation) for emotional processing, there is a
      "left shift" (right visual field advantage) for pro- as opposed to anti-social
      expression. We propose that facial expressions that are likely to be related to
      approach for communicative purposes initiate a greater degree of left hemisphere
      involvement. As a consequence, we suggest that for future laterality studies, the
      six universal emotional expressions should be reconsidered using a pro- to anti
      social dimension rather than positive and negative groupings.

PMID- 15513145
TI  - Hemispheric and facial asymmetry: gender differences.
AB  - Facial asymmetry (facedness) of female and male college students was
      investigated. Comparisons of facedness were made between 45 female and 45 male
      Dartmouth undergraduates. Facedness was defined in terms of the relative sizes
      (in square centimetres) of the two hemifaces. Data were derived from measurements
      of two-dimensional frontal photographs of the subjects. Reliable differences in
      facedness were found between the two groups. The females on average were found to
      be right faced, the males left faced. This difference was interpreted in terms of
      the contralateral control (below the eyes) of the two sides of the face by the
      two hemispheres, and the known differences in cognitive processing by the two
      hemispheres (left hemisphere-verbal; right hemisphere-visuospatial) in females
      and males. The observed difference in facial asymmetry between the two sexes is
      attributed to differential muscular development of the two sides of the face as
      related to the factors just noted. Suggestions are made for further research on
      facedness, particularly in relation to different age groups.

PMID- 15513146
TI  - Self-face identification is increased with left hand responses.
AB  - Evidence suggests that autobiographical memory, self-related semantic category
      judgements, and self-identification tasks may be lateralised, with preferential
      activity in the right anterior temporal and prefrontal cortex. To test this
      hypothesis, participants (N=10) were presented with morphed images of themselves
      (self) combined with a famous face. A further set of images was generated in
      which the face of one of the participant's co-workers (familiar) was combined
      with a famous face. When compared to morphed images composed of a familiar face,
      the participants identified images less often as being famous if the images were
      composed of self, but only when responding with their left hands. This greater
      "self-effect" found in left-hand responses may imply that when the right
      hemisphere is preferentially active, participants have a tendency to refer images
      to self. These data provide further support for a preferential role of the right
      hemisphere in processing self-related material.

PMID- 15513147
TI  - Population lateralisation and social behaviour: a study with 16 species of fish.
AB  - We investigated turning responses in 16 species of fish faced with a vertical-bar
      barrier through which a learned dummy predator was visible. Ten of these species
      showed a consistent lateral bias to turn preferentially to the right or to the
      left. Species belonging to the same family showed similar directions of lateral
      biases. We performed an independent test of shoaling tendency and found that all
      gregarious species showed population lateralisation, whereas only 40% of the non
      gregarious species did so. The results provide some support to the Rogers (1989)
      hypothesis that population lateralisation might have been developed in relation
      to the need to maintain coordination among individuals in behaviours associated
      with social life.

PMID- 15513149
TI  - Language laterality in English/Welsh bilinguals: language-acquisitional and
      language-specific factors in the development of lateralisation.
AB  - In order to test the hypothesis that monolinguals differ from bilinguals in their
      pattern of language lateralisation and to examine the relative merits of language
      acquisitional versus language-specific factors, two experiments involving divided
      screen presentation of two languages were conducted using Welsh/English speaking
      participants. In the first experiment 80 monolingual teenagers were compared to
      80 bilingual teenagers on a tachistoscopic "visual half-field" test of Welsh and
      English nouns and verbs. ANOVA revealed a greater left hemisphere advantage for
      Welsh-English bilinguals as compared to English monolinguals. Thus, in contrast
      to previous studies, in our bilinguals there was evidence of greater left
      hemisphere involvement in the processing of language. In the second experiment,
      four separate groups of 40 teenagers, varying in the age and manner of
      acquisition of their languages, were compared on the same test of Welsh and
      English words. These groups can be viewed as graded from the early to late
      bilinguals. ANOVA revealed a greater left hemisphere advantage when processing
      Welsh as compared to English words for all four groups. However no significant
      difference was observed between the four groups in respect of laterality for
      Welsh and English, indicating an equally greater left hemisphere bias for all
      four groups when processing Welsh words. We discuss these results in terms of a
      language-specific effect and suggest the specific orthography of the Welsh
      language (for individually presented nouns and verbs) promotes a left hemisphere
      advantage over and above language-acquisitional factors.

PMID- 15513150
TI  - Comparative lateralisation patterns in the language area of human, chimpanzee,
      and rhesus monkey brains.
AB  - Lateralised architectural differences in radial cell column structure were
      detected in the planum temporale of humans but were not found in homologous
      regions of ape or monkey brains. This study used a new computer imaging method to
      quantify the architecture of thousands of cortical minicolumns. A study of Lamina
      III in the left hemisphere of human brains revealed a wider separation between
      cell columns and more non-neuronal (empty) space within cell columns compared to
      the right hemisphere. This asymmetry was absent in the chimpanzee brains and
      weakly reversed in the rhesus monkey brains. The results imply an evolution
      towards more clearly defined columnar structures in the left hemisphere of human
      brains compared to those of monkeys.

PMID- 15513151
TI  - The dynamics of two different tests of laterality in rats.
AB  - Female rats were tested for behavioural laterality in a T-maze (TM) and a
      "handling by the tail" (TH) test, and vaginal smears were taken every day. The
      two tests did not correlate. There was a population bias of left choices in TH,
      but in TM most of the animals were ambilateral. Statistical analysis showed that
      animal learning in successive trials influenced their lateral choice, but it was
      similar in both tests. The difference in lateral bias in rats in the two tests
      depended mostly on differences in internal laterality. Rats in proestrus had a
      left-side bias in TM. There was no dependency between direction of lateral choice
      in TH and estrus cycle.

PMID- 15513152
TI  - Organisation of left and right hand movement in a prehension task: a longitudinal
      study from 20 to 32 weeks.
AB  - The organisation of reaching movements was studied longitudinally (every two
      weeks) in infants aged from 20 to 32 weeks, in order to detect possible
      differences between the two hands. An object was presented on a table, at a
      reachable distance, and four trials were retained. Analysis of left and right
      hand movements was performed, frame-by-frame, on video images obtained from two
      cameras. Three body points were considered: the elbow, the wrist, and the major
      finger for drawing the profile of the movement. Three parameters were considered:
      movement time (MT), straightness, and number of changes in direction. Data show
      that the right hand MT is always shorter than the left hand MT. Moreover, the
      right hand is also continuously more directly oriented towards the object and
      makes fewer corrective changes than the left hand. These data show that a
      different organisation of movement of the left and the right hand exists early in
      infancy.

PMID- 15513153
TI  - Dichotically presented emotionally intoned words produce laterality differences
      as a function of localisation task.
AB  - Two-syllable words (burden; furrow; mantle; ration) each spoken in happy, angry,
      sad, and neutral tones of voice were dichotically paired. For each presented word
      pair, subjects were asked to localise ("left"; "right") or reject the presence of
      one pre-specified word on one block of trials and one pre-specified emotional
      tone on a second trial block. Right ear advantages (REAs) indicated by a superior
      hit rate averaging 9.6% were found for all words. Left ear advantages (LEAs)
      averaging 15.2% were obtained for emotional intonation, with additional evidence
      of differences between emotion categories. Results are discussed in terms of
      complementary hemispheric roles for linguistic and prosodic analysis.

PMID- 15513155
TI  - Lateral inversions and introversion in Ingres.
AB  - The famous French nineteenth-century painter Jean-Auguste-Dominique Ingres
      (17801867) produced in the course of his career several left to right inversions
      of his own figural compositions. Because according to the narrative imagery
      conventions of directional viewing both the original and the reversed scenes
      should be looked at from left to right, the mirror-like reversion results in a
      dramatic alteration of the scenes' meaning. Considering that the literary topics
      that Ingres chose for his pictures often had an affective meaning for him, the
      lateral inversions may have been motivated by a subconscious wish to exorcise
      traumatic memories.

PMID- 15513156
TI  - The leftward cradling bias and hemispheric asymmetry for speech prosody.
AB  - Most women prefer to cradle an infant to the left side. It has been suggested
      that this bias is due to the specialisation of the right hemisphere for emotion,
      but investigations of visual asymmetries found no empirical support for this
      proposal. In a recent article, Sieratzki and Woll (1996) suggested that more
      emphasis should be placed on the auditory, rather than the visual, modality.
      Using a dichotic listening procedure we investigated whether ear preference for
      the perception of emotion in speech was related to the lateral cradling bias.
      Although the findings of both a leftward lateral cradling bias and a left ear
      emotion perception advantage were replicated, we found no association between the
      two variables--and thus fail to support the recent suggestions of a possible
      cause for the lateral cradling bias.

PMID- 15513157
TI  - Cerebral asymmetry of emotion and its relationship to olfaction in infancy.
AB  - To examine the relationship between emotional development and laterality, smells
      differing in affective valence (predetermined by adults) were presented to 10
      neonates. Each infant was presented with two positive and two negative food
      related odorants, each paired with a neutral stimulus. Each pair was presented
      twice, once with the odorant to the right nostril and once to the left nostril.
      These eight trials were repeated in two blocks. In addition, control trials,
      where a puff of air was administered to both nostrils, were included. Head
      turning from midline position to presentation of the odorants as videotaped while
      the infant slept. Direction of initial head turn served as the dependent measure.
      A significant interaction with Smell x Nostril x Direction was found. Post hoc
      analyses revealed that significant effects occurred only for the positive smells.
      When the positive smells were presented to the left hemisphere, neonates made
      significantly more head turns towards the smell. This raises the possibility that
      approach behaviours may develop earlier than withdrawal behaviours.

PMID- 15513158
TI  - Evidence from sentence priming for an atypical language organisation in the brain
      of dyslexic males.
AB  - The present study used an experimental paradigm that combined sentence priming,
      lexical decision, and visual hemifield stimulation to investigate the
      relationship between dyslexia and linguistic processing by the two hemispheres.
      It was predicted that left hemisphere (LH) superiority for word recognition in a
      constraining versus a neutral sentence context would be reduced, or even reversed
      in dyslexic as compared to normal participants. Because both dyslexia and LH
      superiority for language processing are considered to be more prevalent for males
      than for females, it was further expected that this decrease, or reversal, in LH
      superiority for word recognition in a sentence context would be more pronounced
      for males with dyslexia than for females with dyslexia. A total of 88 children,
      half of whom were females, participated in the study: 44 children were diagnosed
      as dyslexic and 44 were normal readers. The results generally confirmed the
      hypothesis and provided strong support for a reversal in hemispheric asymmetry in
      males with dyslexia. Implications for sentence processing of the excessive
      involvement of the right hemisphere (RH) in the dyslexia of males are discussed
      and the lexical-decision-sentence-priming paradigm is recommended as a promising
      means of exploring the issues related to these implications.

PMID- 15513159
TI  - Spatial relations and object processes in two cerebral hemispheres: a validation
      of a sequential matching paradigm for the study of laterality.
AB  - Kosslyn (1987) proposed that categorical spatial relations (i.e., above/below)
      would be processed more effectively in the left hemisphere, whereas coordinate or
      metric relations would be processed more effectively in the right hemisphere. To
      examine his hypothesis, a sequential matching task adopted by Laeng and Peters
      (1995) was administered. In this task, a sample stimulus was presented in the
      central visual field and it was followed by a match stimulus presented briefly in
      the left or right visual field. In Experiment 1, the participants' task was a
      same different discrimination about spatial relations. Participants responded
      faster to categorical changes in the right visual field presentation. This result
      was consistent with Kosslyn's hypothesis. In Experiment 2, participants were
      asked to make same different judgements about objects (either a digit or a
      natural line drawing) irrespective of spatial location. They responded faster to
      digit (i.e., verbal) changes in the right visual field. This result was
      compatible with the classical notion that verbal materials would be processed
      more effectively in the left hemisphere. This evidence suggests that the matching
      paradigm of the present study is useful for investigating cerebral lateralisation
      not only for spatial relations but also for object processes.

PMID- 15513160
TI  - An examination of the hypothesis that left-handers die earlier: the Canadian
      Study of Health and Aging.
AB  - The present paper is a prospective examination, using data from the Canadian
      Study of Health and Aging (CSHA-1 and CSHA-2), of the hypothesis that self
      reported left-handers die earlier than right-handers. Persons over age 65
      receiving a clinical evaluation in 1991 (n = 2786) as part of CSHA-1 were
      recontacted in 19956. At baseline, the sample showed a trend for the expected
      cross-generational decline in nonright-handedness with increasing age (3.2% of
      those aged 6574 reported being left-handers while 2.1% were left-handers in the
      85+ age group). At follow-up, there were no significant differences in mortality
      between self-reported right-handers (52.6% died), left-handers (56.8%), and
      ambidexters (46.6%). The Odds Ratio was 1.18 (95% confidence interval 0.721.93)
      for left- compared to right-handers. There was no evidence that being left-handed
      increased the risk of death in this sample of elderly Canadians.

PMID- 15513161
TI  - Handedness in Colombia: some associated conditions.
AB  - As part of a national neuroepidemiological study a population-based sample of
      6941 subjects, 10 years of age or older, was selected in five different regions
      in Colombia (South America). Overall, 91.65% of the participants (90.6%) of the
      males; 92.7% of the females) considered themselves as right-handers. Handedness
      was significantly correlated with education in men but not in women. Handedness
      was not associated with age. Prevalence of history of loss of consciousness,
      tremors, difficulties with speech, and traumatic head injury was observed to be
      higher in non-handers than in right-handers. This finding was particularly
      evident in men. Implications of current results are analysed.

PMID- 15513162
TI  - Intercorrelations among tests of lateralisation in the BALB/c mouse.
AB  - In order to examine the reliability of lateralised behaviours, BALB/c mice were
      tested in three different situations: the Collins paw preference test (PPT), the
      rotatory swimming test (RST), and the T maze test (TMT). The results showed a
      significant correlation between the scores of lateralisation in the PPT and the
      RST, but a lack of lateralisation in the TMT. Considering the tasks involved in
      these tests, these results appear to support the hypothesis of close links
      between lateralised behaviours, emotional processes, and neural pathways.

PMID- 15513163
TI  - Cerebral asymmetries in the level of attention required for word recognition.
AB  - Words presented to the right visual field (RVF) are recognised more readily than
      those presented to the left visual field (LVF). This RVF advantage could reflect:
      (a) the direct connection between the RVF and left hemisphere, (b) an attentional
      bias directed towards the RVF, or (c) an attentional advantage, where the left
      hemisphere is able to recognise words using less attention than the right
      hemisphere. The attentional bias and advantage models were tested in 20 dextral
      adults during a divided visual field word-naming task. Spatial attention was
      manipulated with valid, invalid, or neutral central cues. Error and reaction time
      measures revealed a RVF advantage for word recognition. If the attentional bias
      model is correct, the RVF advantage should have been attenuated for valid and
      invalid cues compared to neutral cues. Instead of this, an interaction emerged
      whereby the cueing effect was stronger for words in the LVF than the RVF. This
      interaction has been reported previously in studies using peripheral spatial
      cues. The interaction suggests that the RVF requires less attention to process
      words than the LVF. This left hemisphere attentional advantage may reflect
      asymmetries between the hemispheres in their word processing styles.

PMID- 15513164
TI  - Right hemisphere contributions to the comprehension of low-imagery words.
AB  - A priming experiment, with normal university students as subjects, was used to
      investigate whether the right cerebral hemisphere contributes to the
      comprehension of low-imagery words. Each hemisphere's access to semantic
      representations of low-imagery words was gauged by comparing responses to low
      imagery targets preceded by associated low-imagery primes (e.g., BELIEF-IDEAL)
      with responses to the same targets when they were preceded by unrelated primes
      (e.g., FATE-IDEAL). All primes and targets were independently projected to the
      left or right visual fields (LVF or RVF), and temporally separated by a stimulus
      onset asynchrony of 250 ms. There was a clear RVF advantage in response speed and
      accuracy measures, confirming the left hemisphere's advantage in processing low
      imagery words. Nonetheless, the priming effects provided evidence that the right
      hemisphere contributes to the comprehension of low-imagery words, as primes
      projected to the RVF equally facilitated responses to associated targets
      subsequently appearing in either visual field. In contrast, primes directed to
      the LVF did not facilitate responses to associated targets projected to the LVF
      or RVF. The results suggest that low-imagery words projected to the left
      hemisphere activated low-imagery associates in both hemispheres to an equivalent
      degree, whereas low-imagery primes directed to the right hemisphere failed to
      activate low-imagery associates in either hemisphere. Like Kounios and Holcomb's
      (1994) study of event-related response potentials evoked by abstract and concrete
      words, the findings indicate that while the left hemisphere is the primary
      processor of low-imagery/abstract words, the right hemisphere plays a subsidiary
      role in the comprehension of these words.

PMID- 15513165
TI  - Moderating effect of ear preference on personality in the prediction of sales
      performance.
AB  - This study examined the relationship between ear preference, personality, and
      performance ratings on 203 telesales staff. Social desirability scores were a
      significant predictor of two relatively independent sets of supervisor ratings
      (actual performance and developmental potential) in interaction with ear
      preference. It was found that the social desirability scale was a significant
      positive predictor for staff preferring a right ear headset, but a negative
      predictor for staff preferring a left ear headset. These results were interpreted
      in terms of different strategies used to achieve successful sales.

PMID- 15513166
TI  - Can I twist your arm? The influence of target orientation on the magnitude of the
      right-hand advantage.
AB  - Controversy exists concerning whether handedness is a unidimensional trait or a
      multidimensional trait. However, researchers espousing the view that handedness
      is multidimensional are in disagreement regarding what the dimensions are that
      underlie handedness. Healey, Liederman, and Geschwind (1986) have provided some
      evidence that the type of musculature utilised (i.e., proximal versus distal) may
      be an underlying factor in determining handedness. The present research attempted
      to test this notion by examining the effects of target orientation on the
      relative performance of the two hands, using a peg-moving task. Target
      orientation was examined by utilising key-shaped pegs that fit securely into key
      shaped holes. The results showed that the presence of target orientation
      increased the preferred-hand advantage. It is considered that this increased
      advantage for the right hand may be due to the hemispheric control of proximal
      versus distal musculature suggested by Geschwind and Galaburda (1985).

PMID- 15513167
TI  - Genes for left-handedness: how to search for the needle in the haystack?
AB  - Although several genes that determine left-right asymmetry for structural
      syndromes such as situs inversus have been characterised in recent years (Supp,
      Witte, Potter, & Brueckner, 1997), there has been little progress in determining
      which genes or loci predispose to left-right handedness in humans. Linkage
      analysis has been used widely for the localisation of genes followed by their
      positional cloning. The complex genetics of handedness is one of the greatest
      problems for standard linkage analysis. Several genetic models have been proposed
      for the inheritance of handedness in humans. On the basis of these models, left
      handedness can be considered a common single gene trait with a high gene
      frequency and a non-mendelian inheritance pattern. We report here a possible
      strategy, using these genetic models, that can be applied for the identification
      for genes determining handedness in humans.

PMID- 15513168
TI  - Cerebral volumetric asymmetries in non-human primates: a magnetic resonance
      imaging study.
AB  - Magnetic resonance images (MRI) were collected in a sample of 23 apes, 14 Old
      World monkeys, and 8 New World monkeys. The total area or volume of the anterior
      and posterior cerebral regions of each hemisphere of the brain was measured. The
      results indicated that a rightward frontal and leftward occipital pattern of
      asymmetry was present at a population level in the great ape sample. Population
      level cerebral asymmetries were not revealed in the sample of New or Old World
      monkeys. The total area or volume of the planum temporale, which was localised
      only in the great apes, was also measured in both hemispheres. A leftward planum
      temporale asymmetry was evident at the population level in the great apes. It was
      hypothesised that the rightward frontal and leftward occipital asymmetries would
      correlate with leftward planum temporale asymmetries. This hypothesis was based
      on the assumption that, similar to development of the human brain, the nonhuman
      primate brain ''torques'' during development due to a growth gradient which
      progresses anterior to posterior, ventral to dorsal, and right to left. The
      results of this study confirmed the predicted relationship between cerebral
      volume and the planum temporale asymmetries. This supports the hypothesis that
      the great ape brain may develop in a ''torquing'' manner, producing similar
      anatomical asymmetries as reported in humans.

PMID- 15513169
TI  - Testosterone and grasp-reflex differences in human neonates.
AB  - According to the Geschwind-Behan-Galaburda (GBG) hypothesis, prenatal
      testosterone (T) causes a slowing in the development of the left brain with a
      consequent compensatory growth in the right brain, creating a reverse
      organisation of the cerebral lateralisation. That is, left- and right-handedness
      might be associated with high and low prenatal T levels, respectively. To test
      this hypothesis, the relations of T levels (umbilical cord blood) to grasp-reflex
      strengths were studied in human neonates. Handedness was assessed by measuring
      the grasp-reflex strengths from the right and left hands in 10 trials from each
      hand alternatively. There were two handedness groups: right-handers (R-L
      significantly greater than zero) and left-handers (significantly smaller than
      zero). Contrary to the GBG model, the mean free T concentration was found to be
      significantly higher in right-handers than left-handers for males and females.
      There was no significant difference in the total T levels between right- and left
      handers. Free T concentrations positively correlated with RL grasp-reflex
      strengths, i.e. right-handedness increased as T increased, and left-handedness
      increased as T decreased. Contrary to these positive correlations, T negatively
      correlated with the grasp-reflex strengths from the right and left hands. These
      results partly supported the GBG hypothesis for this spinal-motor-asymmetry
      model. Total T did not significantly correlate with grasp-reflex strengths. The
      results suggest that prenatal T may at least play a role in prenatal
      determination of spinal motor lateralisation, with a possible consequent upward
      regulation of cerebral lateralisation.

PMID- 15513170
TI  - Canonical views of faces and the cerebral hemispheres.
AB  - Evidence is given for a special, canonical, status of one specific view in the
      identification of familiar faces. In the first experiment, subjects identified by
      name the fully frontal or profile poses of briefly familiarised individuals less
      efficiently than an intermediate pose. In addition, in a matching experiment
      using faces seen in different poses, it was found that one specific intermediate
      pose (corresponding to 22.5 degrees of angle from the full frontal view) was
      matched more efficiently in the right visual field (RVF) than in the left visual
      field (LVF). This finding supports the hypothesis of a superiority of the left
      hemisphere (LH) over the right hemisphere (RH) in processing a familiar face's
      canonical view. The other tested "noncanonical" views (i.e., full frontal, 45
      degrees, and profile) of these same familiar faces were better matched in the LVF
      (i.e., the RH); especially at low levels of familiarity. We conclude that, for
      each familiar face, a viewer-centred representation of the canonical (22.5
      degrees ) view is stored in the LH's memory system, whereas multiple views of
      familiar faces are stored in a memory system of the RH. With increasing levels of
      familiarity other views are increasingly more efficiently encoded by the LH, and
      in fact for facial self-recognition the full-front view is superior to any of the
      other tested views. These findings taken together suggest that complementary
      lateralised memory subsystems in the two cerebral hemispheres store different
      sets, only partially overlapping, of view-centred face representations.

PMID- 15513171
TI  - Functional asymmetry in the human face: perception of health in the left and
      right sides of the face.
AB  - The expression of health on the human face, like beauty or emotions, is an
      important biological display. Previous findings of left-right functional
      asymmetry in facial attractiveness and the linkage of attractiveness and health
      in evolutionary biology notions have prompted the present study. A total of 38
      pairs of left-left and right-right facial composites were viewed by 24 subjects
      on a computer screen, and the task was to decide which member of the pair looked
      healthier or there was no difference. The results revealed a significant
      interaction between face side and sex of face. Right-right composites of women's
      faces were judged significantly healthier than left-left, whereas in men's faces,
      no significant left-right difference emerged. As these results parallel previous
      findings of attractiveness in the identical set of faces, we propose that
      evolutionary biology notions linking the appearance of health and of
      attractiveness apply to the human face as well.

PMID- 15513172
TI  - Right-sided asymmetry in sensitivity to tickle.
AB  - A standard tickle apparatus was used to apply stimuli to the soles of left and
      right feet of subjects. Subject ratings of the strength of the tickle sensation
      felt after each stimulus revealed that the right foot was significantly more
      sensitive than the left. This effect was independent of both hand and foot
      preference. The results are discussed in relation to other findings on
      lateralisation, and it is suggested that they are consistent with evidence that
      the left hemisphere is more involved in positive emotions.

PMID- 15513173
TI  - Lateral and sex differences in manual gesture during conversation.
AB  - To examine whether sex differences in cerebral lateralisation for speech can be
      observed through lateral differences in manual gesturing during natural
      conversation, 100 individuals (50 male and 50 female) were observed following a
      procedure similar to that described by Kimura (1973a,b). For males, there was a
      significant increase in the number of gestures made with the right hand during
      speech. When males were listening, there was a significant increase in the number
      of gestures made with the left hand. This result was not observed in the females
      studied, who did not demonstrate significant manual asymmetries in gesturing
      during either speech or listening. This result is consistent with claims that
      there is a sex difference in hemispheric specialisation wherein males are more
      functionally lateralised than females.

PMID- 15513174
TI  - Inferring handedness from lithic evidence.
AB  - Until recently research into the origins of human handedness has been hampered by
      the lack of valid techniques for inferring handedness in pre-modern populations.
      A method developed by Toth for inferring handedness from lithic evidence, based
      on orientation of the cortex on lithic flakes, has produced promising results.
      However, this method is limited in applicability and has a variable signal to
      noise ratio. The authors describe a separate method, based on the orientation of
      the cone of percussion in lithic flakes, for inferring handedness from the lithic
      evidence. This method complements the cortex method. Some preliminary
      experimental evidence is presented which indicates that handedness can be
      inferred from lithic evidence using the cone of percussion method. Suggestions
      for further research are made.

PMID- 15513175
TI  - Hand preferences in sign-learning students with autistic disorder.
AB  - The purpose of the study was fourfold: (a) to document the hand preferences of
      nonspeaking individuals with autism as they produced signs and nonsign actions;
      (b) to find out if sign-language proficiency in such individuals is associated
      with directionality or consistency of signing hand preference; (c) to explore the
      link between hand preference for signing and standardised measures of cognitive
      and motor development; (d) to compare the hand preferences (sign and nonsign
      actions) of such individuals to sign-learning children with normal cognitive
      functioning. In this study, the hand preferences of 14 nonspeaking students with
      autistic disorder were determined from videotape records of their sign production
      and nonsign actions. In their sign production, four students strongly favoured
      their right hands, four had a distinct left-hand preference, and six did not
      significantly favour either hand. There was little evidence linking sign-language
      proficiency, cognitive maturity, or motor development to strongly lateralised
      signing or handedness in general in these students. Compared with the hand
      preferences of the children in the two comparison groups, the autistic students
      were markedly less lateralised with respect to signing, but not nonsign actions.

PMID- 15513176
TI  - Hand preference in Italian students.
AB  - Italian undergraduates (N = 2326) were administered the Italian revised version
      of Edinburgh Handedness Inventory (Salmaso & Longoni, 1985). Left-handedness was
      documented in relation to sex, university faculty, geographic origin and
      handedness pressure. A greater proportion (7.9%) of left-handedness was found
      compared to previous works on Italian samples. Additional results indicated a
      difference in left-handedness incidence among Southern, Central and Northern
      Italian regions. Results are discussed in terms of social and cultural influence.

PMID- 15513177
TI  - Brain asymmetry for language in dyslexic children.
AB  - Studies of brain asymmetry in dyslexia have yielded mixed results both with
      respect to patterns of asymmetry and their cognitive correlates. This paper
      assessed language lateralisation inferred from dichotic listening with forced
      attention in a clinical group of young dyslexic subjects. As a whole the dyslexic
      group showed a deviant asymmetry pattern compared to a control group. Subdivision
      into two subgroups by receptive language abilities yielded differential patterns
      within the dyslexia group. Both subgroups exhibited a weaker response pattern to
      right ear stimuli than the control group. In addition, the subgroup with no
      language impairment showed bilateral language representation, whereas the
      subgroup with impaired receptive language abilities showed reversed dominance
      patterns.

PMID- 15513178
TI  - Lateral preference patterns as possible correlates of successfully switched left
      hand writing: data and a theory.
AB  - Left-handers often have had to contend with pressure to switch their preferred
      writing hand and shift attempt reports are common, especially among older adult
      left-handers. Three groups of left-handers can be defined by combining two
      variables, writing hand side and the report of a rightward hand preference shift
      attempt. The three groups are, first, right hand writers who report a rightward
      shift (successfully shifted left-handers); second, left hand writers who report a
      rightward shift attempt (unsuccessfully shifted left-handers); and, finally, left
      hand writers who do not report a rightward shift attempt. The underlying
      mechanisms that determine the success or failure of a handwriting shift attempt
      remain unclear. The present study examined the history of attempts to switch the
      preferred writing hand in a sample of 1277 adults aged 65 to 100 years of age.
      Older adults are well suited to participate in such a study because pressure to
      switch hand preference was especially severe for those who grew up in the early
      part of the 20th century; reports of rightward shift attempts are more common in
      this age group than among younger adults. Our results suggest that the three
      groups of left-handers, distinguished by the presence or absence of a shift
      history report and writing hand side, can also be distinguished from each other
      on the basis of their overall lateral preference profiles (the sides of hand,
      foot, eye, and ear preferences). Left hand writers, with and without reports of a
      rightward shift history, showed stronger left side lateralisation patterns when
      compared to right hand writers who reported a rightward switch (the successfully
      shifted left-handers).

PMID- 15513179
TI  - Reliability and magnitude of visual laterality effects: the influence of
      attention.
AB  - Two studies investigated the test-retest reliability of laterality effects in
      visual tasks. In each of the studies, 160 right-handed participants were tested.
      In Experiment 1, a lexical decision task was used under four testing conditions:
      no control of attention, fixation control, bilateral presentation with endogenous
      cue, and bilateral presentation with exogenous cue. In Experiment 2, the same
      four conditions were used in a letter-matching task in which participants had to
      indicate whether two letters in a different case had the same name. Results
      showed a significant right visual field advantage in the first testing session.
      However, this advantage was eliminated in the second session, suggesting that
      attention was not fully controlled by any of the procedures. In addition, the
      reliability of laterality effects was greater when control of attention was
      applied. The discussion focuses on the importance of controlling attention when
      assessing laterality by means of a visual task. Alternative explanations of the
      present findings are also considered.

PMID- 15513180
TI  - Hemispheric asymmetry in the induction of false memories.
AB  - The purpose of this study was to investigate hemispheric asymmetry in verbal
      memory by using a false recognition paradigm and a standard list learning
      paradigm, which can induce high false recognition for semantically related
      distractors. The experiment showed that the LH could discriminate the targets
      from the related distractors more accurately than the RH. This result was
      attributed to the hemispheric difference in the hit rate rather than in false
      recognition. The results of the present study suggest that the model of RH coarse
      semantic coding and LH fine semantic coding is applicable not only to language
      processing but also to verbal memory.

PMID- 15513181
TI  - A kinematic analysis of hand selection in a reaching task.
AB  - A group of left- and right-handers was tested on a task requiring them to reach
      out and pick up an object with either the left or the right hand. We varied the
      eccentricity of the target object (a small glass) and the required accuracy
      level, by filling the glass with liquid. We recorded (a) frequency of left or
      right hand use, (b) hand preference using a handedness questionnaire, and (c) the
      trajectories of the reaches using a movement registration system. It was found
      that the stronger the hand preference, the further in contralateral space the
      shift occurred between left and right hand use. Not only did the transition point
      corresponding to the shift between the two hands correlate with the point where
      their deceleration times were equal, but these locations closely coincided. These
      findings suggest that people are highly skilled perceivers of their own action
      capabilities, and that they are able to select the action mode that is most
      suited to perform a given task. We argue that laterality should be understood in
      terms of asymmetries in action modes.

PMID- 15513182
TI  - A paradox in the laterality of melody processing.
AB  - Melody lateralisation has been examined extensively, using well known behavioural
      techniques--dichotic/monaural listening and dual tasks. The literature using
      these techniques has produced paradoxical results for the lateralisation of
      melody processing particularly with non-musicians. Research using the
      dichotic/monaural listening paradigm suggests right hemisphere processing for non
      musicians while the dual task paradigm has suggested a left hemisphere dominance.
      The current study utilises both monaural listening and dual task techniques
      within trials. The results replicated the paradox in the literature. The
      dichotic/monaural listening melody measure (d') suggest right hemisphere
      processing of melodies for both musicians and non-musicians. In contrast, the
      dual task measure suggests left hemisphere processing for the non-musicians and
      bilateral processing for the musicians. Both measures were collected from the
      same stimulus presentations and are therefore paradoxical particularly for the
      non-musicians. Irrespective of which task participants are primarily attending,
      both laterality measures should produce internally consistent patterns if they
      are measuring the same aspects of melody processing. Although the paradox for the
      musicians may be resolved by postulating an attentional bias towards the tapping
      task, no such explanation is possible for the non-musicians. In light of the
      paradoxical findings produced by these two measures, their utility for providing
      unambiguous information about lateralisation of mental processing is
      questionable.

PMID- 15513184
TI  - Preferential limb use in relation to epicoracoid overlap in the shoulder girdle
      of toads.
AB  - We studied left-right asymmetry in forelimb and hindlimb use in green toads (Bufo
      viridis) and fire-bellied toads (Bombina bombina) and investigated its possible
      relationship to the asymmetric structure of the shoulder girdle (epicoracoid
      overlap) in the latter species. To estimate forelimb use preference we used a
      modified ''snout-wiping test'' (Bisazza et al., 1997) and to estimate hindlimb
      use preference we used the ''righting response test'' (Robins et al., 1998). The
      position of epicoracoids in living animals was determined as proposed earlier
      (Borkhvardt & Malashichev, 1997). We also examined behavioural laterality in B.
      viridis to check whether B. viridis is a left-handed species, as it was not clear
      from the previous study. Our results showed that B. viridis predominantly used
      the left forelimb and left hindlimb in experimental situations at both the
      population and individual levels. The same tests were applied to fire-bellied
      toads, B. bombina, with right or left epicoracoids in the top (dorsal) position.
      We found that (1) B. bombina is mostly a symmetric species, sometimes using both
      hands or feet simultaneously; (2) it is ambidextrous in hand and foot use with
      non-significant left side preference at the population level; (3) there is a
      positive and significant concordance between the position of epicoracoids and the
      forelimb preference in B. bombina. Animals with the right epicoracoid in the
      dorsal position (R. top = L. superficial) prefer to use the right forelimb in the
      ''snout-wiping test'' and L. top animals predominantly use their left forelimb.

PMID- 15513185
TI  - Gestural communication in chimpanzees (Pan troglodytes): the influence of
      experimenter position on gesture type and hand preference.
AB  - This study examined the influence of experimenter position on hand use in
      gestural communication in a sample of 127 captive chimpanzees. Hand use in
      gestural communication was recorded while an experimenter was positioned either
      left, right, or directly in front of the subject. The type of gesture was also
      recorded as either a food beg or whole hand point. Both hand use and gesture were
      consistent across experimenter positions. Overall, a significant population-level
      right hand bias was found, particularly for food beg gestures. These results are
      consistent with previous findings in chimpanzees and suggest that lateralisation
      in gestural communication is left hemisphere dominant.

PMID- 15513186
TI  - Mean mortality among Brazilian left- and right-handers: modification or selective
      elimination?
AB  - Many surveys report a higher incidence of left-handedness in younger than in
      older cohorts, and explanations for this phenomenon have centred around two rival
      hypotheses. The modification hypothesis attributes this trend to secular
      differences in the social tolerance of left-handed preferences, whereas the
      elimination hypothesis contends that left-handers have a shorter life-span than
      right-handers do, and hence are infrequent in the population above age 70. In
      order to evaluate these two hypotheses, data were collected on 513 decedents from
      kin informants. There were 465 right- and 48 left-handed decedents, including 18
      switched sinistrals. Females lived significantly longer than males, and there was
      a nonsignficant survival advantage for left-handers. Switched left-handers were
      disproportionately represented among older compared to younger decedents,
      indicating an historical reduction of sanctions against left-handed writing.
      These results contradict the survival advantage for right-handers reported by
      Coren and Halpern (1991), providing evidence more favourable to a cultural
      conditioning explanation, rather than one emphasising selective mortality.

PMID- 15513187
TI  - Fluctuating asymmetry and the human brain.
AB  - Adaptive development requires the organism to resist genetic and environmental
      stresses that disrupt the genetic plan for growth, a buffering capacity termed
      developmental stability. Developmental instability is revealed by fluctuating
      asymmetry (FA), which has been demonstrated in many species to reflect phenotypic
      and genetic quality. We report (1) that a measure of developmental instability
      based on body FA predicts deviation from typical brain asymmetry, (2) that a
      combined measure of atypical brain asymmetry and body FA correlated negatively
      with the area of the corpus callosum, especially the portion connecting the left
      and right planum temporale, and (3) that this combined measure also predicted
      atypical asymmetry of the size of the somatosensory representation of the two
      hands, as determined from magnetic source imaging.

PMID- 15513188
TI  - Hemispheric specialisation, spatial activity experience, and sex differences on
      tests of mental rotation ability.
AB  - A sex difference in mental rotation ability is well established. Among the
      explanations offered for this difference are that males are more frequently right
      hemisphere specialised for spatial processing and that they receive more spatial
      processing experience because of the sex stereotyping of activities involving
      spatial ability that exists in Western societies. Several studies have shown that
      males do report more spatial activity experiences on the Spatial Activity
      Questionnaire of Newcombe, Bandura, and Taylor (1983) and that such experience
      does correlate with performances on tests of mental rotation. However, two prior
      lateralised tachistoscopic studies failed to show right hemisphere superiority
      for spatial task performance or that it was positively associated with better
      performances on the Vandenberg Mental Rotation Test. The tachistoscopic tasks
      used in these studies can be criticised on methodological grounds. The present
      study employed a new tachistoscopic task that showed that males were
      significantly more right hemisphere specialised (left visual-field superior) for
      the tachistoscopic task than females. Magnitudes of right hemisphere
      specialisation on the tachistoscopic task were positively and significantly
      related to mental rotation ability. Spatial activity experiences were also more
      common in males. Covariance and partial correlation analyses indicated that the
      sex difference in spatial ability was primarily due to sex differences in right
      hemisphere specialisation for mental rotation, while sex differences in spatial
      activity experiences were only secondarily involved.

PMID- 15513189
TI  - Ambidexterity and magical ideation.
AB  - In a sample of 250 healthy undergraduate students, scores on a scale of magical
      ideation rose to a peak at the point of ambilaterality on a scale of hand
      preference, and fell away with increasing right- or left-handedness. This effect
      mirrors that reported by Crow, Crow, Done, and Leask (1998) who found a dip in
      academic abilities at the point of ambilaterality, or what they call ''the point
      of hemispheric indecision''. We relate these findings to genetic theories of
      laterality in which one allele (RS+) codes for left-cerebral dominance while the
      other (RS-) leaves laterality to chance. RS-- homozygotes may be susceptible to a
      lack of dominance, resulting in a disposition to magical ideation and an
      increased risk of schizophrenia, but also enhanced creativity and lateral
      thinking.

PMID- 15513190
TI  - Hemispheric interaction and consciousness: degree of handedness predicts the
      intensity of a sensory illusion.
AB  - It has been suggested that the two cerebral hemispheres play different roles in
      the maintenance and updating of an individual's beliefs. In particular it has
      been suggested that the left hemisphere (LH) forms consistent beliefs, whereas
      the right hemisphere (RH) monitors for inconsistencies or anomalies in reference
      to these beliefs. If some threshold of inconsistencies is detected, the role of
      the RH is to update the LH's belief system accordingly. Handedness may reflect
      the degree to which the two hemispheres exchange information such that the more
      strongly handed an individual is, the less interhemispheric communication may
      take place, thus attenuating this updating process. Two studies were carried out
      that confronted participants with conflicting, anomalous sensory information by
      tapping on both the participant's real hand and a fake hand in synchrony. One
      conclusion would be to update the LH belief system to include the fake hand as
      their own and consciously experience the taps as coming from the fake hand. It
      was predicted that this experience would vary with handedness such that the more
      strongly handed a participant was, the less they would experience the sensory
      illusion. Study 1 supported this, with more strongly handed participants
      reporting lesser degrees of the illusion. A second study replicated this effect
      and included a variable that measured the time it took for a participant to
      experience the illusion. A non-significant trend was present such that more
      strongly handed participants were slower to experience the illusion. Last,
      although the illusion was felt equally in both the left and right hand
      conditions, correlations between handedness and the illusion were only present in
      the left hand condition. A model of how interhemispheric interaction may function
      in maintaining beliefs and consciousness is presented.

PMID- 15513191
TI  - Brain metabolic differences as a function of hemisphere, writing hand preference,
      and gender.
AB  - A total of 35 university-educated normal men (24 right handwriters and 11 left
      handwriters) and 36 age- and education-matched women (25 right handwriters and 11
      left handwriters) underwent a proton magnetic resonance spectroscopy examination
      in seven 8 cm(3) voxels including the right and left frontal lobe tips, the right
      and left mid-temporal lobes, the right and left thalami, and the hypothalamus.
      Dependent measures were N-acetylaspartate (NAA), choline-containing compounds
      (Cho) and creatine/phosphocreatine (Cr) metabolite peak area ratios relative to
      total H(2)O. As expected, thalamic grey matter contained higher NAA ratios than
      telencephalic voxels (containing white and grey matter) (p < .001). The thalamic
      Cr/ H(2)O ratio was higher on the right, but the opposite asymmetry was observed
      for the temporal lobe (p < .05). Women had a higher left frontal NAA/ H(2)O ratio
      than men, but men had a higher hypothalamic NAA/ H(2)O ratio than women. Right
      handers had a higher temporal lobe NAA/H(2)O ratio than left-handers,
      particularly in the left hemisphere. In addition, several significant 2- and 3
      way interactions between writing hand preference, gender, and hemisphere were
      observed, but only in the frontal lobe.

PMID- 15513192
TI  - Measuring handedness: a validation study of Bishop's reaching card test.
AB  - The aim of the study was the validation of Bishop's reaching card test (Bishop et
      al., 1996) in a French population. Annett's peg-moving test (1985) and the Purdue
      pegboard (Tiffin, 1948) were also used to assess manual performance. Subgroups of
      left- and right-handers were established according to manual preference as
      measured by Annett's questionnaire (1985). A sample of 260 adults was tested,
      including 158 self-professed right-handers, 77 self-professed left-handers, and
      25 self-professed ambidextrous people. The three manual performance tests and the
      questionnaire presented good metric qualities (homogeneity, test-retest
      reliability). However the constitution of subgroups of laterality (in particular
      left-handers) as a function of manual preference could not be validated by
      classic tasks, or by Bishop's test, which is supposed to combine features of both
      preference and performance. Moreover the link between performance and preference
      was weak. Both evaluations should be used to produce a complete pattern of
      laterality for each participant.

PMID- 15513193
TI  - Manual asymmetries in tool-use: implications for apraxia.
AB  - Previous examinations of manual performance asymmetries have utilised relatively
      simple movements such as goal-directed aiming and rapid finger-tapping. In the
      present research, three-dimensional kinematic analyses were employed to examine
      manual asymmetries in the production of transitive limb gestures. Transitive limb
      gestures involve the use of tools and/or objects and are complex movements used
      in the evaluation of limb apraxia. Ten healthy right hand dominant participants
      produced two transitive limb gestures in response to verbal command both with
      (tool-use) and without (pantomime) the appropriate tool. Analyses revealed a
      dominant (right) hand advantage, although the magnitude of this advantage was
      influenced by movement context (pantomime vs tool-use). This study provides the
      first evidence that manual asymmetries are elicited during the production of
      transitive limb gestures, and mandates that future kinematic analyses of limb
      apraxia consider the impact of pre-morbid manual asymmetries when contrasting the
      performance of left and right hemisphere damaged patients.

PMID- 15513194
TI  - Leading-limb preferences in marmosets (Callithrix jacchus): walking, leaping and
      landing.
AB  - The leading-limb preferences of 17 common marmosets (Callithrix jacchus) when
      they initiated and terminated locomotion were determined from video recordings of
      the subjects walking on, leaping off, and landing on a plexiglas platform. In a
      majority of sequences, 11 of 17 subjects landed with the right hand and foot
      contacting the plexiglas substrate before the left hand and foot. Of the 17
      subjects, 8 initiated leaping with the right side of the body, whereas only 3
      subjects significantly preferred to initiate leaping with the left hand and foot.
      Leading-limb preferences displayed during landing were positively correlated with
      those displayed for leaping and walking, although only two subjects displayed
      significant leading-limb preferences when walking. By contrast, hand preferences
      for initiating and terminating locomotion were not related to hand preferences
      for food holding; 16 of 17 marmosets displayed strong and significant hand
      preferences for food holding, even though many did not show leading-limb
      preferences for walking, leaping, or landing. These data seem to suggest that the
      right arm is stronger in marmosets. The right arm is used initially to decelerate
      the body and absorb the impact of contact with the landing substrate. The
      tendency for the right arm to be stronger is balanced by a tendency for the left
      leg to be stronger (providing the force needed for leaping).

PMID- 15513195
TI  - Lateralisation of predator avoidance responses in three species of toads.
AB  - Lateralisation of responses to presentation of a simulated predator was
      investigated in three species of toads: two European species (the common toad,
      Bufo bufo, and the green toad, Bufo viridis) and one species introduced to
      Australia from South America, the cane toad Bufo marinus . First a simulated
      snake was presented moving rapidly towards the toad in the frontal field of
      vision and the toad's escape responses, including jumps to the right and to the
      left, were recorded. No significant bias in left or right side jumping was
      apparent in this test. Next the simulated snake was presented in the left or
      right lateral field of vision in random order. Escape and defensive responses
      were elicited more strongly, in all three species, when the stimulus was on the
      toad's left side compared to its right side. Reaction times scored in the
      experiments with B. marinus, alone, did not differ from left to right. There
      were, however, species differences in the types of escape responses with respect
      to the laterality: B. viridis and B. marinus showed similar patterns of more
      sideways jumps with left presentation and more frontal jumps with right
      presentation. Sideways jumps were not lateralised in B. bufo, but this species
      showed more frontal jumps when the presentation was on the left side. These
      findings suggest that the selective involvement of structures located in the
      right side of the brain (left monocular visual field) in emotional responses
      (particularly fear responses) could be a phylogenetic ancient trait.

PMID- 15513198
TI  - Asymmetries in amphibians: a review of morphology and behaviour.
AB  - Morphological and behavioural asymmetries in amphibians are reviewed. Among the
      characteristics considered are: (1) the asymmetry of the shoulder girdle
      (epicoracoid overlap); (2) the distribution of the left and right variants of its
      structure in amphibian populations; (3) asymmetry in the position of the
      spiracle(s); (4) asymmetric order of forelimb emergence from opercular chambers
      in tadpoles; and (5) preferential forelimb use in adult amphibians. I show that
      there are no direct cause-and-effect relationships between these characteristics,
      which would explain their development. Other asymmetries, such as asymmetry of
      the visceral organs, turning behaviour of tadpoles, asymmetries in the length and
      weights of the long bones, and some neuromorphological traits, also show few
      examples of relationships. However, the simultaneous absence of many asymmetries
      in some amphibians and their presence in others suggests a common cause, which
      affects all of these asymmetries indirectly, presumably very early in
      ontogenesis.

PMID- 15513199
TI  - Lateralised brain function in anurans: comparison to lateralisation in other
      vertebrates.
AB  - In recent years researchers have begun to investigate lateralisation of behaviour
      in amphibians. Given the mounting evidence of lateralisation in birds and
      mammals, and even reptiles, over the past two or more decades, it is not
      surprising that amphibians have attracted attention in this context. In
      particular, the evidence for lateralisation in fish has provided a strong basis
      for this research. This paper summarises the currently available information on
      lateralisation in anuran amphibians and discusses it in comparison to
      lateralisation in other vertebrate species, beginning with examples of motor
      lateralisation and then discussing functional asymmetries that occur between the
      left and right sides of the brain. The latter are manifested as side biases in
      responding to different stimuli or, in a number of non-amphibian species,
      revealed by monocular testing. Most of the examples discussed refer to
      lateralisation present at the level of the forebrain hemispheres, and so
      represent hemispheric specialisation. Lateralisation usually refers to examples
      in which there is a population bias for the majority of individuals in a
      population to be lateralised in the same direction. In other words, there is a
      significant skew in the frequency distribution. Such population biases in
      lateralisation are now known to be widespread among the vertebrates and, as
      shown, there are some surprisingly similar patterns of lateralisation in those
      species of fish, amphibians, reptiles, birds, and mammals that have been studied
      so far. It is also noted that, despite their ubiquity in vertebrates, far from
      all forms of lateralisation develop solely, or even largely, according to genetic
      determinants. In fact, the clear and powerful influences of environmental
      stimulation on development of some kinds of lateralisation in birds provide a
      basis for similar investigations in anurans.

PMID- 15513200
TI  - Assessing and interpreting lateralised behaviours in anuran larvae.
AB  - We review here what is known about lateralised behaviours in tadpoles, focusing
      on turning biases and methods for testing them. Two testing protocols have been
      used that are specific for explosive turns which are likely to be Mauthner cell
      mediated. They involve recording the turns made by tadpoles: (1) upon descent
      after they take a breath of air, and (2) after they are mechanically startled.
      Turning bias has also been explored for tadpoles: (3) in a T-maze, (4) as they
      exit a tube into a larger arena, and (5) as they turn away from a barrier or
      object brought towards their snout. Slower turns observed under the last three
      protocols may not be regulated by the same neuromotor pathways as the faster
      turns elicited in the first two protocols. Turning biases do not occur in
      tadpoles of all species. In species where turning biases have been observed
      during explosive turns, the biases are typically towards the left side. The
      majority of tadpoles have a single asymmetric left-sided spiracle, yet
      lateralised behaviours in these tadpoles do not appear to be obligatorily linked
      to this morphological asymmetry. Tadpole turning biases are usually of the order
      of 60-90% towards the preferred side and are rarely absolute for individuals, and
      never for populations. Turning biases, when present, usually appear shortly after
      hatching and disappear before metamorphosis. Turning biases that appear during
      metamorphosis may depend on appendicular rather than axial muscle, and thus are
      fundamentally different behaviours; i.e., involving different neuromuscular
      components. Lateralised behaviours may occur in anurans before they reach the
      free-living larval stage. This could include bias in the side towards which a
      frog embryo coils its tail within the egg case, or the side towards which a newly
      hatched tadpole leans when lying on the bottom How lateralised behaviours of
      anurans that change with ontogeny relate to each other is not known Although it
      has been suggested that turning biases are absent in the more archaic frog genera
      only two 'archaic' genera have been examined Xenopus and Bombina and the data are
      too few to discern any clear phylogenetic patterns Lastly we present a model
      suggesting why tadpoles might have turning biases in situations where maximum
      speed is paramount This model assumes that the fastest neuromotor programs will
      be 'hardwired' in the central nervous system The model predicts that the amount
      of morphological asymmetry in the Mauthner neurons will be directly proportional
      to the amount of turning bias seen in tadpoles.

PMID- 15513201
TI  - Limb preference and skeletal asymmetry in the cane toad, Bufo marinus (Anura:
      Bufonidae).
AB  - Two forms of skeletal asymmetry were identified in a population of cane toads,
      Bufo marinus, an exotic species in Australia. Fluctuating asymmetry characterised
      the lengths and weights of the long bones of the forelimbs and hindlimbs.
      Directional asymmetry was observed in the structure of the pectoral girdle of the
      toads, with the right epicoracoid positioned ventral to the left epicoracoid in
      88% of the skeletons examined. Morphological data from a cohort of individuals
      were correlated with limb preferences determined from 10 consecutive trials in
      which the toads were inverted and briefly submerged in water while bilaterally
      clasping the experimenter's fingers. The toad's left forelimb was released first
      to enable the right forelimb to exert force against the experimenter's fingers
      and so control righting the body of the toad in 90% of trials. Asymmetries in the
      long bones of the forelimbs and pectoral girdles of the toads did not correlate
      significantly with the strength of preference for the right forelimb, although
      asymmetry of the weight of the tibiafibulae did correlate significantly with
      percent right forelimb preference. Age, or nutritional status, was a factor in
      the right forelimb preference: the preference for the use of the right forelimb
      was strongest in toads possessing longer and heavier long bones of both the
      forelimbs and hindlimbs. These results provide insight into the interaction
      between skeletal development and lateralised motor behaviour in an anuran
      species.

PMID- 15513202
TI  - Behavioural and morphological asymmetries in hindlimbs of Hoplodactylus
      duvaucelii (Lacertilia: Gekkonomorpha: Gekkota: Diplodactylinae).
AB  - This study reports an association of behavioural and morphological directional
      asymmetries at the level of individual lizards. I counted all subdigital lamellae
      (scales) under the toes of 57 Hoplodactylus duvaucelii on North Brother Island,
      New Zealand. Geckos released first from the substrate the hindlimb that had fewer
      subdigital lamellae than the other hindlimb. Analyses of data from the literature
      show that in geckos, clinging ability increases with the number of subdigital
      lamellae, especially after variation in body mass is accounted for. Assuming that
      grasping (an active process) and clinging (a passive process) abilities are
      correlated, the association of behavioural and morphological asymmetry among
      individuals could be interpreted in functional terms: geckos lift first from the
      substrate the hindlimb that has the lowest ability to stick to the substrate.

PMID- 15513203
TI  - Display lateralisation in the courtship behaviour of the alpine newt (Triturus
      alpestris).
AB  - Among urodelan amphibians, European newts of the genus Triturus have evolved a
      complex sequence of displays to the effect of stimulating the female to actively
      pick up the spermatophore deposited by the male. Courtship is varied, with plenty
      of potential for asymmetric uses of tails and of asymmetric turns. The analysis
      of the temporal structure of the behavioural sequences showed that both males and
      females significantly utilise the same side during a single courtship sequence.
      Moreover, if an individual prefers to exhibit one side during its lateral
      displays, then the duration of its displays on that side is longer than the
      duration of its displays on the other side. The only significantly contralateral
      display is creep-on. Less than 50% of the alpine newts show a significant left-
      or right-side preference and no lateral bias at population level was found. At
      the population level, male Triturus vulgaris showed a marked bias towards left
      turning after spermatophore deposition, in spite of the existence of both "left
      turning" and "right-turning" individuals in the population (Green, 1997). The
      presence of population biases may be adaptive if it can influence the sensory
      processes and the motor responses involved in social interactions. In fact,
      Triturus vulgaris is characterised by a more complex courtship sequence than T.
      alpestris and by complex male-male interference mechanisms, but no selective
      advantages were shown for either left- or right-turning males (Green, 1997).

PMID- 15513204
TI  - Determinants of handedness in twins.
AB  - It is well established that the distribution of the combinations of handedness
      (LL, LR, and RR) in twin pairs is roughly binomial regardless of zygosity or sex.
      This fact has challenged current genetic models of handedness. We show here that:
      (a) there must be at least one environmental determinant of handedness; and (b)
      the binomial distribution does not in itself invalidate genetic models of
      handedness. In singletons, left-handedness is strongly associated with low birth
      weight. In twins, this association is weaker (apparently as a consequence of a
      stronger association with birth order--i.e., with being first-born--within the
      pair). We speculate that the hazards associated with being first-born in twin
      pairs (e.g., trauma) are more closely associated with left-handedness than are
      the hazards associated with being second-born (e.g., hypoxia).

PMID- 15513205
TI  - Does "callosal relay" explain ear advantage in dichotic monitoring?
AB  - Pairs of consonant-vowel (CV) syllables were dichotically presented to a large
      sample of healthy subjects (n = 263) who were instructed to monitor for the
      presence of a target CV (/ta/) which could occur in either ear. The subjects
      responded by pressing a response button, allowing the recording of reaction times
      (RTs) and number of correct responses. The investigated sample comprised
      consistent right-handers (CRH), consistent left-handers (CLH), and mixed-handers
      (MH). It was found that right-ear targets were detected more frequently and
      faster than left-ear targets, both in CRH and MH subjects. CLH subjects, on the
      other hand, responded faster to targets presented to the left ear but there was
      no ear advantage in terms of the correct responses. The RT data were used to
      examine whether they are compatible with the callosal relay model of language
      lateralisation. It was found that the predictions made by the callosal relay
      model were supported by the RT data for all groups.

PMID- 15513206
TI  - Hand preference and hand skill in families with schizophrenia.
AB  - Direction and degree of handedness in humans are variable between individuals and
      thought to be in part inherited. Several studies have shown an increase in non
      right handedness among patients with schizophrenia, and some have included
      unaffected relatives. The present study was designed to determine whether reduced
      right handedness is more frequent among individuals with schizophrenia as
      compared with their well relatives and whether it clusters within families having
      multiple ill members. A total of 259 families comprising 418 individuals
      diagnosed with schizophrenia or schizoaffective disorder, 54 individuals with
      other psychoses, 145 family members with depression and other minor diagnoses,
      and 288 unaffected individuals were included. Hand preference was assessed by the
      Annett Scale and right relative to left hand skill measured using the Tapley
      Bryden test. For all assessments of hand preference and hand skill, females were
      significantly more lateralised towards the right than males. Those individuals
      with schizophrenia or schizoaffective disorder had significantly less right hand
      preference than their unaffected relatives when measured as a quantitative index
      of items from the Annett Scale (p = .019), but not categorically (right, left or
      mixed). In contrast, there was no difference in hand skill between diagnostic
      groups. Hand preference was significantly correlated among male-male affected
      sibling pairs (p = .01) and similar results were found for hand skill among the
      total group of affected pairs (p = .001). Although these results only partially
      support a relationship between handedness and schizophrenia, they nevertheless
      draw attention to sex differences in hand preference and the familial aspects of
      hand preference in this disorder. More direct approaches to the genetics of
      cerebral dominance and psychosis are required.

PMID- 15513207
TI  - Hemispheric asymmetries in global-local perception: effects of individual
      differences in neuroticism.
AB  - This study examined the impact of neuroticism on hemispheric specialisation and
      interhemispheric processing using a lateralised global-local perception task. A
      total of 43 individuals completed the laterality task as well as a standardised
      personality questionnaire, and were divided by a median split into low and high
      neuroticism groups. Results revealed that left hemisphere specialisation for
      local-level processing was absent for high neurotic individuals, although the
      groups were similar in asymmetries for global-level processing. Regression
      analyses confirmed that neuroticism was inversely correlated with the magnitude
      of left-hemisphere advantage for local-level processing but not associated with
      the asymmetry for global processing. Interhemispheric processing did not differ
      as a function of neuroticism. Results implicate the left temporoparietal region
      in neuroticism, which may in turn have implications for understanding
      neuropsychological links between neurotic personality traits and risk for
      psychopathology.

PMID- 15513208
TI  - Left cradling and left ear advantage for emotional speech: listen to the other
      side too.
AB  - In a recent issue of this journal, Turnbull and Bryson (2001) examined a possible
      relation between left ear (right hemisphere) advantage for perception of
      emotional speech and the universal preference of mothers to cradle infants on the
      left side, referring to a hypothesis that we had previously suggested (Sieratzki
      & Woll, 1996). Although they concluded that their data do not support our theory,
      reanalysis does suggest a connection between the hemispheric asymmetry for speech
      prosody and the leftward cradling bias.

PMID- 15513209
TI  - The leftward cradling bias and audition: cross-modal confusion? A response to
      Sieratzki, Roy, and Woll.

PMID- 15513210
TI  - Handedness is associated with immune functioning and behavioural reactivity in
      rhesus macaques.
AB  - In the present study we examined the relationship among handedness, immune
      functioning, and behavioural reactivity in rhesus macaques. We used the absolute
      number of CD4+ (T-helper) and CD8+ (T-suppressor) cells as dependent measures of
      immune functioning. We derived reactivity profiles from behavioural responses to
      a threat, and hand preference profiles from a quadrupedal food-reaching test. The
      results indicate positive correlations between the frequency of right versus left
      hand reaches and the absolute number of CD4+ cells, and between the frequency of
      right versus left hand reaches and the degree of human-directed aggression in
      response to an invasive threat. Immune measures were not associated with the
      strength of hand preference. These results are consistent with and extend
      previous findings obtained with rodents to nonhuman primates and provide further
      support for the view that behavioural lateralisation is associated with immune
      functioning and behavioural reactivity.

PMID- 15513211
TI  - Ground scratching and preferred leg use in domestic chicks: changes in motor
      control in the first two weeks post-hatching.
AB  - Lateralisation of a variety of visual functions: food discrimination, fear
      response, copulation, and performance of topographical and other tasks, such as
      olfactory and auditory functions, have been described in the domestic chick,
      Gallus gallus domesticus. A bias to left hemisphere control on day 8 and to the
      right on day 11 has also been demonstrated in the domestic chick. In this study
      we show that motor control as to foot preference in initiating a scratching bout
      and a tape-removing task is lateralised in both adults and chicks. There was a
      preference for the right leg to initiate a bout of ground scratching in both male
      and female adult birds. Second, foot preference is also affected by the changes
      in shifts of bias on day 8 and day 11. The right leg preference in initiating a
      ground scratching bout observed on day 5 is reversed to a left leg preference on
      day 8. This then reverts to the right leg preference after day 11. Hence it is
      postulated that the hemisphere that is not activated due to the bias of age
      controls the first leg to be used in initiating routine movements such as ground
      scratching. For the tape-removing task the right leg was used to remove a tape
      adhered to the beak of the chick for the trained group on day 8; but there was no
      preference in the naive group. Similarly, on day 11 a left foot bias was observed
      for the trained group and right foot bias for the naive group. To remove a tape
      the activated hemisphere on days of bias is used; whereas in a novel situation
      the foot use is reversed. Thus, footedness is affected by age, type of task, and
      changing hemispheric dominance.

PMID- 15513212
TI  - No go on neutrals? An interhemispheric account of semantic category priming.
AB  - In a divided-visual-field priming paradigm, participants made manual lexical
      decisions performing either go no-go responses, or yes-no responses, to related
      prime-target word pairs that were nonassociated, category members (DEER-PONY).
      Half of each response group received unrelated (ATTIC-PONY) baselines and half
      received neutral (BLANK-PONY) baselines. In the go no-go response, small but
      reliable priming was obtained in both target visual fields and there was a
      reliable slowing of response time in the right visual field/left hemisphere for
      participants receiving the neutral baseline. In the yes-no response, greater
      priming was obtained from a neutral baseline, as compared to an unrelated
      baseline. We show that under appropriate conditions priming for these stimuli
      occurs in both visual fields. We also report that cross-visual-field advantages
      emerged as cognitive task load increased across combinations of baseline and
      response variables. We conclude that task load may be as important a factor in
      priming asymmetries as SOA or type of semantic relationship.

PMID- 15513213
TI  - Reliability and magnitude of visual laterality effects: further examination of
      the endogenous cueing procedure.
AB  - The present study tests the hypothesis that laterality effects with bilateral
      displays would be larger and more reliable when lexically matched stimulus pairs
      are used rather than unmatched pairs. A total of 40 right-handed participants
      completed a lexical decision task using matched stimulus pairs in a bilateral
      display. These data were added to a previously collected set of data with 40
      right-handed participants in which unmatched stimulus pairs were used. Results
      showed that the expected right visual field advantage (RVFA) was significant in
      words but not in non-words. In addition, a significant practice effect was found
      to be larger for matched than unmatched stimulus pairs. The predicted interaction
      between stimulus type, stimulus pairing, and visual field was not significant;
      contrary to the initial hypothesis, the RVFA was larger (though not significantly
      so) for unmatched displays than for matched ones. Finally, the laterality effect
      was found to be more reliable with unmatched than matched pairs in non-words,
      whereas no difference was found in words. The discussion emphasises the
      advantages of unmatched stimulus pairs and the conditions under which the
      bilateral effect is likely to emerge.

PMID- 15513214
TI  - The effects of reading-writing direction on the asymmetry of space perception and
      directional tendencies: a comparison between French and Tunisian children.
AB  - We compared the influence of reading and writing habits on the asymmetry of space
      perception and the directional tendencies of French and Tunisian right-handers,
      aged 5, 7, and 9 years. By comparing two groups of children who use the opposite
      direction for writing (from left to right for French, from right to left for
      Arabic), before and after being taught to read in school, we evaluated the impact
      of writing direction on these asymmetries. A bisection task, a circle-drawing
      task, and a dot-filling task were used to assess spatial asymmetries and
      directional tendencies. On the bisection task, a group difference emerged at 9
      years, with the French children bisecting the line to the left of the true
      centre, and the Tunisian children showing no bias. On the circle-drawing task,
      there was a group difference from 7 years on, as the French children, but not the
      Tunisian children, used increasing counterclockwise movements. Finally, on the
      dot-filling task performed with the right hand, the French children filled in
      significantly more dots when going from left to right from 7 years on, whereas
      Tunisian children filled in more dots when going from right to left. These
      results show the impact of basic tendencies in younger children (ipsilateral bias
      in line bisection, clockwise direction in circle drawing, outward tendency for
      horizontal displacement in dot filling), as well as the impact of writing
      direction on spatial asymmetries after learning to read. The results are also
      discussed in reference to the differences between the two languages, the
      closeness of the French direction of writing to spontaneous neural-based
      tendencies, and the influence of learning French at age 8 for the Tunisian
      children.

PMID- 15513215
TI  - Reduction of lateral asymmetries in dribbling: the role of bilateral practice.
AB  - The influence of bilateral practice on the modification of well-established
      lateral asymmetries of performance was investigated in overlearned motor skills
      related to soccer in 12- to 14-year-old adolescent players. The participants had
      extensive practice before entering the experiment and were trained 2 hours per
      day, five times per week, during a period of 4 months. In the training, the
      participants were assigned to one of two groups: practice with emphasis on the
      preferred leg (PL), or practice with emphasis on the nonpreferred leg (NpL).
      Lateral asymmetries of performance were assessed before and after training on
      three motor tasks: kicking for force, kicking for accuracy, and speed of
      dribbling. The analysis of the results indicated a consistent asymmetry of
      performance throughout the tests, favouring the preferred leg. The asymmetry of
      performance was maintained at a constant level across the tests for the kicking
      tasks in both experimental groups. For speed of dribbling, however, the index of
      lateral asymmetry was reduced from the pre- to the post-test in the NpL group
      only, which was due to a higher rate of improvement with the nonpreferred leg
      after the experimental training. These results are indicative of the role played
      by bilateral practice in modifying lateral asymmetries of performance established
      as a consequence of previous unilateral training.

PMID- 15513216
TI  - Visual lateralisation in quails (Coturnix coturnix).
AB  - Two-week-old quails (Coturnix coturnix) were trained to discriminate food grains
      scattered randomly on a background of small pebbles of similar size adhering to
      the floor and differing from the grains in texture and hue ("pebble floor task").
      Quails tested binocularly or with only their right eye in use showed less pecking
      to the pebbles and more pecking to the grains than quails tested with only their
      left eye in use. Adult quails in contrast did not show lateralisation. These
      findings add to previous evidence for visual lateralisation in birds in the
      pebble floor task suggesting that neural structures fed by the right eye, mainly
      located to the left hemisphere, are better suited to rapid visual categorisation
      of food objects. Like other galliformes species such as the domestic chick
      (Gallus gallus), but unlike non-galliformes species such as the pigeon,
      behavioural lateralisation in the pebble floor task may be associated with
      transitory anatomical asymmetries in the thalamofugal visual pathway.

PMID- 15513217
TI  - The development of motor asymmetries in 1-month-old infants who were prenatally
      exposed to cocaine.
AB  - The development of motor asymmetries was assessed in 20 infants who were
      prenatally exposed to cocaine and 23 comparison infants. Asymmetries in stepping,
      grasping, and head orientation were assessed at 1 month of age. As expected based
      on the findings of previous research with high-risk infants, infants who were
      prenatally exposed to cocaine performed a grasping task with their right hand for
      significantly shorter durations than comparison infants and were less likely to
      show a dominant hand preference than comparison infants. Comparison infants were
      also more likely to display a side bias for head orientation and stepping than
      infants who were prenatally exposed to cocaine. These findings suggest that
      prenatal exposure to cocaine may alter the typical developmental trajectory of
      functional asymmetries and may have important implications for long-term
      developmental outcomes.

PMID- 15513219
TI  - What to do about your child's handedness? Advice from five eighteenth-century
      authors, and some questions for today.
AB  - On the question "What to do about your child's handedness?", parents have never
      lacked for advice. Over more than two millennia, however, their advisors have
      rarely spoken with one voice. Instead, they have disagreed on virtually
      everything, including the desirability of handedness, its origins in nature or
      nurture, and especially the acceptability and treatment of left-handedness. After
      briefly describing such disagreements from classical times, this article presents
      and analyses new examples from the works of five authors in the eighteenth
      century, three from England ("An Eminent Physician", William Cadogan, and John
      Hill) and two from France (Nicholas Andry and Jean-Jacques Rousseau). It then
      presents similar examples from more recent authors, and it concludes by asking
      what advice about handedness the current generation of laterality researchers
      would be prepared to offer.

PMID- 15513220
TI  - Multiprocess lateralisation in dyslexia.
AB  - Previous studies of behavioural asymmetries in dyslexia have emphasised verbal
      measures, and have not generally supported differences in functional asymmetry
      between dyslexic and normal readers. Here a multiprocess approach is taken,
      employing a sample of adult dyslexic readers. An unusual pattern of
      lateralisation is found for bargraph recognition, a visual spatial quantitative
      task. Unlike the right hemisphere pattern found in normal readers, dyslexic
      readers appear to perform spatial quantitative processing in the left hemisphere.
      These results are consistent with parietal lobe dysfunction in reading
      disability, and more specifically with an angular gyrus dysfunction as suggested
      by recent MRI and PET results. Possible causes are discussed for this right-to
      left shift in function, in the face of a left-to-right shift in brain tissue
      reported in the literature.

PMID- 15513221
TI  - Left-handedness is correlated with CSF monoamine metabolite and plasma cortisol
      concentrations, and with impaired sociality, in free-ranging adult male rhesus
      macaques (Macaca mulatta).
AB  - In this research we examined biological and behavioural correlates of handedness
      in free-ranging adult male rhesus macaques (Macaca mulatta). Specifically, we
      examined relationships between handedness and cerebrospinal fluid (CSF)
      concentrations of the monoamine metabolites 5-hydroxyindoleacetic acid (5-HIAA),
      homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG), plasma
      concentrations of the hormones cortisol and adrenocorticotropin (ACTH), and
      multiple indices of social behaviour, including occurrences of proximity to other
      animals, grooming, submission, and aggression. We determined handedness through
      systematic observation of animals reaching for food in their unrestricted home
      environment. The frequency of right- versus left-hand use was significantly
      positively correlated with CSF 5-HIAA, CSF MHPG, and plasma cortisol
      concentrations, and with social proximity and the frequency and duration of bouts
      in which animals received grooming. The frequency of right- versus left-hand use
      was significantly negatively correlated with the frequency of submissive
      behaviour, and with the frequency and intensity of bouts in which animals
      received aggression. We conclude that handedness is associated with an array of
      biological and behavioural processes in free-ranging adult male rhesus macaques
      and that left-handedness may be used to identify individuals at increased risk
      for impaired functioning of the serotonin, norepinephrine, and hypothalamic
      pituitary-adrenal systems, and for social isolation and susceptibility to violent
      attack.

PMID- 15513222
TI  - Orthographic and phonological priming in the two cerebral hemispheres.
AB  - The patterns of activation invoked in the two cerebral hemispheres by written
      words may be different. Two lexical decision experiments investigated several
      aspects of such activation patterns. Experiment 1 tested phonological and
      orthographic priming in the hemispheres, manipulating two levels of phonological
      and two levels of orthographic similarity. Orthographic priming in the left
      visual field (LVF) was significantly larger than in the right visual field (RVF).
      In Experiment 2, primes were phonologically identical to the targets (homophones)
      but differed in their orthographic similarity. For LVF targets, only orthographic
      priming was significant, whereas for RVF targets, the phonological primes were
      effective regardless of their orthographic similarity. The results imply that
      orthographic activation, though maintained by both hemispheres, is more
      characteristic of right hemisphere word recognition processes, whereas
      phonological priming is more characteristic of left hemisphere processes.

PMID- 15513223
TI  - Relationship between facial asymmetry and judging trustworthiness in faces.
AB  - Nonverbal facial signals provide valuable information for successful social
      interactions. Previous findings showed left-right facial asymmetry in
      attractiveness, smiling, and health in faces, and here we investigated the
      asymmetrical status of trustworthiness. Pairs of left-left and right-right faces
      from 38 photographs were viewed by participants who judged which member of the
      pair looked the most trustworthy. The results were compared to attractiveness and
      smiling judgements (Zaidel, Chen, & German, 1995). We found that trustworthiness
      was more related to attractiveness than to smiling in the women's faces, but no
      significant asymmetry for trustworthiness was found; in the men's faces,
      trustworthiness was neither related to attractiveness nor to smiling, nor was
      there a significant asymmetry. Taken together, trustworthiness as a facial
      display is complex; even when it appears to confirm the "halo effect", its
      expression is not strongly left-right asymmetrical in contrast to attractiveness
      or smiling.

PMID- 15513224
TI  - Do the French and the English differ for hand skill asymmetry? Handedness
      subgroups in the sample of Doyen and Carlier (2002) and in English schools and
      universities.
AB  - Doyen and Carlier (2002) reported peg-moving performance in a sample of French
      adults classified in the hand preference subgroups of Annett (1970, 1985). The
      findings were said to differ from those for English samples. This paper describes
      new analyses of English data, drawn from schools and universities. Comparison of
      the school and university samples showed that relationships between hand skill
      asymmetry and subgroup handedness were reliable, but also revealed a new finding.
      Asymmetries were stronger in the school than university samples at all levels of
      hand preference. The French findings resembled those for the English university
      sample for all measures and for all subgroups except right-handed writers with
      strong left tendencies. The performance of the latter in the French sample was
      like that of left-handers rather than right-handers. An explanation might be that
      some members of this group were left-handers who had been forced to use the right
      hand for writing.

PMID- 15513225
TI  - The left human speech-processing cortex is thinner but longer than the right.
AB  - We present histological data from 21 post-mortem, adult human cases that indicate
      the neocortex on the left planum temporale (secondary auditory cortex) is thinner
      but longer than that on the right side. The volumes of the left and right regions
      are approximately equal. Thus, the left planum temporale cortex is long and thin
      and the right short and thick. The present data fit excellently with previous
      studies of the volume, surface area, cytoarchitectonics, and neuronal structures
      of these areas. From these studies we suggest that the hemispheric differences
      arise from a so-called "balloon model" of cortical development. In this the
      cortex is extended and stretched by white matter growth. The stretching is
      greater on the left side, leaving greater distances between neuronal columns and
      more tangentially (to the pial surface) oriented dendrites on that side. This
      difference in fine structure can result in more independent activity of
      individual columns on the left, and could be an anatomical factor in the usual
      dominance of the left hemisphere for speech perception (Seldon, 1982, 1985).

PMID- 15513226
TI  - Adaptations of writing posture in response to task demands for left- and right
      handers.
AB  - Handedness and writing posture are visible manifestations of differences between
      left- and right-handers. Although an inverted posture is witnessed in both
      groups, there is a much higher proportion of left-handers who invert. This study
      is framed within the adaptation hypothesis of writing posture, which states that
      invertedness in left-handers develops in response to the demands of cursive
      writing. Participants (N = 57) comprising left-handed inverters, left-handed
      standard writers, and right-handed standard writers engaged in tasks that
      required them to form letters and pen strokes at extreme angles. In addition
      participants were questioned about attempts to change writing posture. We
      hypothesised that letter angle controls posture in both left- and right-handers
      and that inverted posture would be a target of intervention. The results of the
      study showed some support for these hypotheses in that left- and right-handers
      adapted their posture in response to the constraints placed upon them and
      inverters reported more intervention.

PMID- 15513227
TI  - Age-related changes in hemispheric asymmetry depend on sex.
AB  - A total of 92 participants, 50 younger (mean age 26.3 years) and 42 older (mean
      age 63.8 years), were tested for visual-field asymmetries. On a word-matching
      task, a right-visual-field (RVF) advantage increased with age, consistent with
      the theory that right-hemispheric function shows relatively greater decline with
      age than left-hemispheric function. On a figural-comparison task, a left-visual
      field (LVF) advantage was marginally decreased with age in the men, but
      significantly increased in the women, probably because age-related changes in
      hormonal levels are more pronounced in women. This increase in LVF advantage is
      contrary to both the HAROLD theory that hemispheric asymmetry declines with age,
      and the theory of relative right-hemispheric decline.

PMID- 15513229
TI  - Manual skill, hand skill asymmetry, and cognitive performances in young children.
AB  - A total of 1022 children aged 3 to 6 years were examined in their preschools and
      27% of them were followed up for 2 years. A computerised version of the peg
      moving task was used repeatedly to assess hand skill of the dominant and the
      nondominant hand. Cognitive performance was repeatedly evaluated by tasks
      involving speech, vocabulary, phonological memory, and visual-spatial skills.
      Results showed that: (i) age, sex, and handedness effects on hand skill asymmetry
      generally confirmed previous reports, especially by Annett (2002); (ii) visual
      spatial and vocabulary tasks were significantly related to hand skill but speech
      and phonological memory tasks were not, and the role of the dominant and
      nondominant hand were similar; (iii) overall, manual laterality indexes were only
      weakly associated to some cognitive abilities; (iv) early manual skill was more
      strongly associated to cognitive tasks than later manual skill. These results fit
      the assumption of a significant role of early manual behaviour in aspects of
      cognitive development not relying exclusively on phonology, and raise questions
      about cognitive development and rehabilitation of children with early occurring
      manual deficiencies.

PMID- 15513230
TI  - Hand preference and risk of injury among the Northern Finland birth cohort at the
      age of 30.
AB  - The aim of this study is to examine two hypotheses. The first hypothesis proposes
      that left-handers have a higher injury risk than right-handers. The second
      hypothesis assumes that ambidextrous people have an elevated risk of injury
      compared with both right- and left-handers. The subjects of this study, 4107 men
      and 4461 women, were all born in northern Finland with expected dates for birth
      in 1966. They filled out a questionnaire at the age of 31. In the questionnaire,
      7.9% of the men and 6.1% of the women reported themselves to be left-handers, and
      1.7% of the men and 0.6% of the women to be ambidextrous. In addition, 71% of the
      subjects reported having been involved in at least one injury during their
      lifetime. There was no significant difference in injury involvement between left-
      and right-handers or ambidextrous people. The right-handers reported even more
      injuries in several injury types than did the left-handers. However, men using
      both hands equally had slightly elevated risk of traffic and home injury, whereas
      ambidextrous women had slightly elevated risk of work injury compared with right
      handers.

PMID- 15513231
TI  - Handedness, measures of hemispheric asymmetry, and lateralised lexical decision.
AB  - The goals of the present study were to evaluate the differences between measures
      of lateralisation in the human brain derived from a dichotic listening (DL) task
      and from a task involving identification of visually presented consonant-vowel
      consonant (CVC) nonwords, and to correlate these lateralisation indices with
      performance on a lexical decision task involving visually presented words and
      nonwords. Visual stimuli were presented either in a central position, or to the
      left or right of fixation. Left-handed and right-handed participants completed
      each of the three tasks. Lateralisation indices were derived from performance on
      the DL and CVC tasks, and latency and accuracy measures of lexical decision
      performance were obtained for targets presented centrally and parafoveally.
      Lateralisation indices for left-handed and right-handed participants differed
      significantly for both tasks, and the two lateralisation indices had different
      pattern of correlation with lexical decision performance for left- and right
      handers. For left-handers, lateralisation indices derived from the (visual) CVC
      task were correlated with lexical decision response latency for targets in
      central and left visual field. For right-handers, lateralisation indices derived
      from the (auditory) DL task were correlated with lexical decision response
      latency for targets in central and right visual field. A possible explanation for
      this finding is that the two laterality measures reflect specialisation for
      different types of linguistic processing in the human brain.

PMID- 15513235
TI  - Asymmetries in activation and arousal may contribute to lateralised effects of
      habituation and contingency learning during a repetitive choice reaction time
      task.
AB  - This study presents experimental data that suggest possible hemispheric
      asymmetries in contingency learning and habituation following irrelevant or
      warning stimuli during a discrimination reaction time task. A total of 68 college
      students participated in a letter-categorisation task (presumably engaging the
      left hemisphere more than the right hemisphere) and a visuospatial task
      (presumably engaging the right hemisphere more than the left hemisphere), both of
      which involved making a decision based on two consecutive stimuli. Without prior
      knowledge, one group received warning signals contingent with the reaction
      stimuli, while the other group was exposed to erratic and irrelevant signals
      throughout the tasks. Analysis of the data showed that a warning signal improved
      contingency learning in the letter-categorisation, but not in the visuospatial
      task, while an irrelevant signal led to habituation in the visuospatial, but not
      in the letter-categorisation task. These results are explained in terms of
      hemispheric asymmetries in arousal and activation, as originally suggested by
      Tucker and Williamson (1984).

PMID- 15513236
TI  - Leading limb preference during brachiation in the gibbon family member, Hylobates
      syndactylus (siamangs): a study of the effects of singing on lateralisation.
AB  - Individual-level lateralisations are common among vertebrates, however population
      level preferences are usually reserved for specific tasks. In humans, handedness
      is thought to be related to the hemispheric processing of specific aspects of
      language, including speech. Although nonhuman primates do not possess speech,
      gibbons are known to produce elaborate vocal displays often referred to as song.
      To investigate the evolutionary effects of singing on hand preference, this study
      examined leading limb preference during brachiation in the large-bodied,
      melodious gibbon, Hylobates syndactylus (siamangs). A total of 13 male and 12
      female siamangs were observed in captive and semi-captive settings for leading
      limb preference during vocal and nonvocal behaviour. No significant results were
      found for the effect of vocalisation at the group level, although individual
      level data indicated a trend towards a right shift in the vocal condition,
      especially for females, where 8 out of 12 demonstrated a greater reliance on a
      right leading limb during the vocal versus nonvocal conditions. Males were not
      found to possess significant preferences in either the vocal or nonvocal
      conditions alone, however when condition data were combined, the number of
      individual males lateralised was significantly greater than predicted by chance.
      These findings support individual, but not population-level, effects for
      vocalisation on leading limb preference in siamangs, and emphasise the importance
      of testing for sex difference in handedness and lateralisation research.

PMID- 15513237
TI  - Left- and right-handed children's drawing performance: is there any difference?
AB  - The aim of the present study was to investigate the effect of hand preference on
      children's drawing development. An equal number of left- and right-handed
      children (N = 182), aged 7 to 12 years were asked to complete four different
      drawing tasks. During the drawing process, directionality of horizontal,
      vertical, and circular strokes as well as sequencing was recorded. Each drawing
      was scored according to the developmental stage to which is corresponded. It was
      found that drawing performance improved with age, irrespectively of hand
      preference and sex. In other words, left- and right-handers' drawing performance
      across the four tasks was not found to differ significantly. The only consistent
      difference between the two groups involved was in the production of horizontal
      lines. The results are discussed in terms of implications for questions about the
      lack of differences in left- and right-handed children's drawing performance.

PMID- 15513238
TI  - Towards an improved measure of the Edinburgh Handedness Inventory: a one-factor
      congeneric measurement model using confirmatory factor analysis.
AB  - The Edinburgh Handedness Inventory was administered to a sample of 203 mentally
      well adults drawn from the Western Australian Family Study of Schizophrenia (90
      men and 113 woman). Confirmatory factor analysis demonstrated that seven out of
      ten original items of the Edinburgh Handedness Inventory were sufficient to
      provide an internally consistent and valid measure of hand preference. Exclusion
      of three problematic items led to a more refined measurement of the latent
      construct of handedness. The rationale for exclusion was: (1) redundancy stemming
      from collinearity between writing and drawing, and (2) an unacceptably large
      measurement error associated with two of the items (use of broom and opening a
      box-lid). The results suggest that this revision of the Edinburgh Handedness
      Inventory enhances its measurement properties.

PMID- 15513239
TI  - Context effects in pseudo-neglect measured with a free vision Landmark task.
AB  - Previous studies have shown that neglect patients exhibit a crossover effect on
      free vision line-bisection tasks; they place the cross mark too far right for
      long lines, but too far left for short lines. This is partially determined by the
      relative line length within a block of testing. The purpose of the present study
      was to determine whether the crossover that has been observed in normal
      participants might also be due to the context in which the line is presented. All
      participants were tested on the free vision Landmark task, in which they were
      shown a line that had been correctly bisected, and asked whether the cross mark
      appeared to be too far to the left or too far to the right. In Study 1 half of
      the participants were exposed only to short lines (1-8 cm) and half were exposed
      only to long lines (8-28 cm). Unlike the results for neglect patients,
      performance appeared to be influenced only by the actual length of the line, not
      the relative length. In Study 2 the background on which the lines were presented
      was manipulated. For half of the trials the line appeared on the standard US
      legal-sized paper. For the other half the width of the background was doubled.
      Unexpectedly, no crossover occurred for the wide field width. The results of
      Study 1 suggest that normal participants may be less influenced by context than
      neglect patients. The results of Study 2 suggest that the crossover effect may be
      influenced by some type of interaction between the line itself and the background
      on which it is presented.

PMID- 15513240
TI  - Interhemispheric interaction and beliefs on our origin: degree of handedness
      predicts beliefs in creationism versus evolution.
AB  - It has been suggested that strongly handed individuals have attenuated systems
      for updating beliefs compared to mixed handers (Niebauer, Aselage, & Schutte,
      2002). The current research extended this theory to individual differences in
      updating beliefs concerning our origins. Although the theory of evolution has
      gained overwhelming success in the sciences, a significant percentage of the
      population believes in biblical creationist accounts of human origins that are
      inconsistent with accepted, contemporary scientific views. If strongly handed
      individuals possess attenuated systems for updating beliefs, they might be more
      likely to believe in creationism. In two studies, strongly handed participants
      were more likely to believe in creationism while mixed-handed participants were
      more likely to believe in evolution. A model of how interhemispheric interaction
      functions in maintaining and updating beliefs is discussed. Specifically, mixed
      handedness seems to be associated with a lower threshold for updating beliefs.

PMID- 15513241
TI  - Are there lexicons?
AB  - Many models of the processing of printed or spoken words or objects or faces
      propose that systems of local representations of the forms of such stimuli-
      lexicons--exist. This is denied by partisans of the distributed-representation
      connectionist approach to cognitive modelling. An experimental paradigm of key
      theoretical importance here is lexical decision and its analogue in the domain of
      objects, object decision. How does each theoretical camp account for our ability
      to perform these two tasks? The localists say that the tasks are done by matching
      or failing to match a stimulus to a local representation in a lexicon. Advocates
      of distributed representations often do not seek to explain these two tasks;
      however, when they do, they propose that patterns of activation evoked in a
      semantic system can be used to discriminate between words and nonwords, or
      between real objects and false objects. Therefore the distributed-representation
      account of lexical and object decision tasks predicts that performance on these
      tasks can never be normal in patients with an impaired semantic system, nor in
      patients who cannot access semantics normally from the stimulus domain being
      tested. However, numerous such patients have been reported in the literature,
      indicating that semantic access is not needed for normal performance on these
      tasks. Such results support the localist form of modelling rather than the
      distributed-representation approach.

PMID- 15513242
TI  - Effects of unilateral distractors: a comparison of eye movement and key press
      responses.
AB  - We compared the effects of a unilateral distractor on the latencies of voluntary
      eye movements and key press responses in order to elucidate some of the
      differences between these two types of response with respect to processing
      distractors. On each trial, participants indicated the colour of a central patch
      by making a left or a right response. The colour of the distractor either matched
      the target colour or matched the colour associated with the incorrect response.
      Similarly, the side of the distractor corresponded to the side of either the
      correct or the incorrect response. The results showed that side congruency
      exerted a main effect only on eye movement responses, but colour congruency
      affected eye movement and key press responses similarly. Moreover, when we made
      the target more distinct from the distractor, only distractors that appeared on
      the same side as the response elicited a colour congruency effect, for both
      response modalities. We propose that (1) the appearance of the distractor
      activates oculomotor cells, which facilitate a subsequent eye movement with the
      same direction vector, (2) the distinctiveness of the target determines whether
      colour and side congruency interact, and (3) spatial codes mediate the
      interaction between colour and side congruency that occurs when the target is
      sufficiently distinct from the distractor.

PMID- 15513243
TI  - Nonword repetition in lexical decision: support for two opposing processes.
AB  - We tested and confirmed the hypothesis that the prior presentation of nonwords in
      lexical decision is the net result of two opposing processes: (1) a relatively
      fast inhibitory process based on global familiarity; and (2) a relatively slow
      facilitatory process based on the retrieval of specific episodic information. In
      three studies, we manipulated speed-stress to influence the balance between the
      two processes. Experiment 1 showed item-specific improvement for repeated
      nonwords in a standard "respond-when-ready" lexical decision task. Experiment 2
      used a 400-ms deadline procedure and showed performance for nonwords to be
      unaffected by up to four prior presentations. In Experiment 3 we used a signal-to
      respond procedure with variable time intervals and found negative repetition
      priming for repeated nonwords. These results can be accounted for by dual-process
      models of lexical decision.

PMID- 15513244
TI  - Priming for new associations in animacy decision: evidence for context
      dependency.
AB  - In four experiments we investigated the context-dependent nature of semantic
      memory by looking at priming effects in animacy decision for newly formed
      associations. The first experiment investigated whether the priming effect
      depended on the nature of the prior relation between the word pairs. The results
      showed no such effect, replicating earlier findings. Experiments 2, 3, and 4
      investigated the role of context overlap between study and test. In Experiment 2
      priming for new associations was found only for word pairs that had been
      presented in the animacy decision task during study. Experiment 3 showed that in
      order to obtain priming effects for new associations these associations have to
      be studied in a study task that is aimed at unitized processing of the word pair
      at a semantic level. Experiment 4 showed that processing the pairs as separate
      words at an orthographic level cancelled the priming effect. The results are
      explained by assuming that priming results from the overlap of features that are
      activated during both study and test.

PMID- 15513245
TI  - Abstractionist versus exemplar-based theories of visual word priming: a
      subsystems resolution.
AB  - Three experiments addressed abstractionist versus exemplar-based theories of the
      visual representations underlying word priming. Participants first read centrally
      presented whole words (each displayed in all lowercase or in all uppercase
      letters), and then they completed laterally presented word stems (each displayed
      in all lowercase or in all uppercase letters). Word stem completion priming was
      letter-case specific (greater for same-case primed items than for different-case
      primed items) when stems were presented directly to the right cerebral hemisphere
      but not when stems were presented directly to the left cerebral hemisphere. This
      interaction was not influenced by the typicality of the test stems, but it was
      observed only for stems composed of letters with visually dissimilar lowercase
      and uppercase structures (e.g., bea/BEA) and not for stems composed of letters
      with visually similar lowercase and uppercase structures (e.g., sco/SCO). In
      contrast, cued recall was letter-case specific when similar-case or dissimilar
      case stems were presented directly to the right hemisphere. Results do not
      support strongly abstractionist or exemplar-based theories. Instead, they suggest
      a resolution to these differing perspectives: Relatively independent neural
      subsystems operate in parallel to underlie abstract-category and specific
      exemplar priming of word forms.

PMID- 15513246
TI  - Feedforward and feedback consistency effects for high- and low-frequency words in
      lexical decision and naming.
AB  - In three experiments, we examined feedforward and feedback consistency effects in
      word recognition. Feedforward consistency is the degree to which a word's
      pronunciation is consistent with that of similarly spelled words, and feedback
      consistency refers to whether there is more than one way to spell a
      pronunciation. Previously, Stone, Vanhoy, and Van Orden (1997) reported
      feedforward and feedback consistency effects for low-frequency words in a lexical
      decision task. We investigated the effect of feedforward and feedback consistency
      for both high- and low-frequency words in lexical decision and naming. In both
      tasks, we found that feedforward and feedback inconsistent words were processed
      more slowly than consistent words, regardless of word frequency. These findings
      indicate that both types of consistency are involved in visual word recognition.

PMID- 15513247
TI  - The difference between generating counter examples and using them during
      reasoning.
AB  - The aim of this article is to provide insight into the types of long-term
      knowledge that are used for solving causal conditional inferences. Two taxonomies
      were constructed to map the types of counter example. The available counter
      examples are traditionally probed via a counter example generation task. We
      observed that there are some significant differences in the types of counter
      example retrieved in the reasoning task versus the generation task. The
      generation task can be used for predicting answers that sprout from a reasoning
      process that takes counter example into account, but some participants use a
      different reasoning process in which the available semantic information is not
      used as contrasting evidence. Nonetheless, we found that the results of the
      generation task validly predicted the proportion of inferences accepted as well
      as the number of counter examples used during reasoning.

PMID- 15513248
TI  - Irrelevant sound disrupts speech production: exploring the relationship between
      short-term memory and experimentally induced slips of the tongue.
AB  - To explore the relationship between short-term memory and speech production, we
      developed a speech error induction technique. The technique, which was adapted
      from a Japanese word game, exposed participants to an auditory distractor word
      immediately before the utterance of a target word. In Experiment 1, the
      distractor words that were phonologically similar to the target word led to a
      greater number of errors in speaking the target than did the dissimilar
      distractor words. Furthermore, the speech error scores were significantly
      correlated with memory span scores. In Experiment 2, memory span scores were
      again correlated with the rate of the speech errors that were induced from the
      task-irrelevant speech sounds. Experiment 3 showed a strong irrelevant-sound
      effect in the serial recall of nonwords. The magnitude of the irrelevant-sound
      effects was not affected by phonological similarity between the to-be-remembered
      nonwords and the irrelevant-sound materials. Analysis of recall errors in
      Experiment 3 also suggested that there were no essential differences in recall
      error patterns between the dissimilar and similar irrelevant-sound conditions. We
      proposed two different underlying mechanisms in immediate memory, one operating
      via the phonological short-term memory store and the other via the processes
      underpinning speech production.

PMID- 15513250
TI  - Object-based processes in the planning of goal-directed hand movements.
AB  - Theories in motor control suggest that the parameters specified during the
      planning of goal-directed hand movements to a visual target are defined in
      spatial parameters like direction and amplitude. Recent findings in the visual
      attention literature, however, argue widely for early object-based selection
      processes. The present experiments were designed to examine the contributions of
      object-based and space-based selection processes to the preparation time of goal
      directed pointing movements. Therefore, a cue was presented at a specific
      location. The question addressed was whether the initiation of responses to
      uncued target stimuli could benefit from being either within the same object
      (object based) or presented at the same direction (space based). Experiment 1
      replicated earlier findings of object-based benefits for non-goal-directed
      responses. Experiment 2 confirmed earlier findings of space-based benefits for
      goal-directed hand pointing movements. In Experiments 3 and 4, space-based and
      object-based manipulations were combined while requiring goal-directed hand
      pointing movements. The results clearly favour the notion that the selection
      processes for goal-directed pointing movements are primarily object based.
      Implications for theories on selective attention and action planning are
      discussed.

PMID- 15513251
TI  - Mental model construction in linear reasoning: evidence for the construction of
      initial annotated models.
AB  - According to the mental model theory, reasoners build an initial model
      representing the information given in the premises. In the context of relational
      reasoning, the question arises as to which kind of representation is used to cope
      with indeterminate or multimodel problems. The present article presents an array
      of possible answers arising from the initial construction of complete explicit
      models, partial explicit models, partial implicit models, a single "isomeric"
      model, or a single annotated model. Predictions generated from these views are
      tested in two experiments that vary the problem structure and the number of
      models consistent with the premises. Analyses of the premise processing times,
      answering times and accuracy show that the annotated model yields the best fit of
      the data. Implications of these findings for the mental model theory as developed
      for relational reasoning are discussed.

PMID- 15513252
TI  - How long do the advantages of learning to read a transparent orthography last? An
      investigation of the reading skills and reading impairment of Welsh children at
      10 years of age.
AB  - Spencer and Hanley (2003) showed that Welsh-speaking children aged between 5 and
      7 years who were learning to read Welsh (a transparent orthography) performed
      significantly better at reading both real words and nonwords than did English
      speaking children living in Wales who were learning to read English (a deep
      orthography). In this study, the reading skills of these children were reexamined
      three years later, during their sixth year of formal reading instruction. The
      children learning to read English continued to perform poorly at reading low- and
      medium-frequency irregular words but no differences were observed in reading
      regular words or nonwords. These findings emphasize how long it takes to acquire
      a large sight vocabulary in English, but indicated that the reading skills of the
      majority of the English-speaking children had caught up with those of their Welsh
      speaking counterparts. However, the poorest 25% of the English readers continued
      to perform much worse than the lowest performing 25% of Welsh readers on both
      words and nonwords. An underachieving tail of this kind was not observed in the
      reading performance of the Welsh-speaking group. Overall, these findings suggest
      that in the long term the detrimental effects of an opaque orthography are most
      damaging to the poorest readers.

PMID- 15513253
TI  - The spatial distribution of attention in perceptual latency priming.
AB  - The spatial distribution of visual attention is a yet unresolved question. One of
      the main topics is whether attention is distributed in a graded fashion around an
      attended location (e.g., Downing, 1988; Zimba & Hughes, 1987). The present
      experiments explore whether, and on which conditions, gradients of attention
      arise and contribute to perceptual facilitation. A masked or unmasked prime
      precedes one of two targets whose temporal order has to be judged. The prime
      captures attention, which shortens the perceptual latency of the primed target
      (perceptual latency priming; Scharlau & Neumann, 2003a; Shore, Spence, & Klein,
      2001). No strong evidence for an attentional gradient was found. (1) Accuracy of
      temporal order judgements was independent of the distance between the two targets
      that were judged. That is, facilitation of the second target by the first target
      was spatially invariant. (2) With targets of short duration, facilitation was
      independent of prime-target distance. (3) With targets of long duration,
      gradients were found: Facilitation declined continuously with distance. Thus,
      long duration of stimuli may be a sufficient precondition for an attentional
      gradient. A control experiment showed that object-based attention contributes
      only marginally to perceptual latency priming.

PMID- 15513254
TI  - Working memory and syllogistic reasoning.
AB  - The purpose of this study was to examine the relation between working memory span
      and syllogistic reasoning performance. In addition, performance for the reasoning
      task was compared to predictions made by mental model theory and the probability
      heuristics model. According to mental model theory, syllogisms that require the
      use of more mental models are more difficult. According to the probability
      heuristics model difficulty is related to the number of probabilistic heuristics
      that must be applied, or (for invalid syllogisms) inconsistencies between the
      derived and correct conclusion. The predictions of these theories were examined
      across two experiments. In general, people with larger working memory capacities
      reasoned better. Also, the responses made by people with larger capacities were
      more likely to correspond to the predictions made by both mental model theory and
      the probability heuristics model. Relations between working memory span and
      performance were also consistent with both theories.

PMID- 15513255
TI  - Deconstructing the Tower of London: alternative moves and conflict resolution as
      predictors of task performance.
AB  - Despite widespread use the cognitive demands of the five-disc Tower of London
      (TOL) are unknown. Research suggests that conflict moves (those that are
      essential to the solution but do not place a disc in its final position) are a
      key aspect of performance. These were examined in three studies via a
      verification paradigm, in which normal participants were asked to decide whether
      a demonstrated move was correct. Experiment 1 showed that individual move
      latencies increase with the number of intermediate moves until the disc is placed
      in its goal position (resolution). Post hoc tests suggested that the number of
      alternative moves and moves to resolve a disc were independent predictors of
      performance. Experiment 2 successfully manipulated these factors in an
      experimental design. Experiment 3 showed that they remain determinants of
      performance as familiarity increased. Overall, errors on the task were
      significantly correlated with spatial memory. The implications of these findings
      for the use of the TOLin cognitive psychology and as an assessment tool are
      discussed.

PMID- 15513256
TI  - Capacity and contextual constraints on product activation: evidence from task
      irrelevant fact retrieval.
AB  - Three experiments tested the limiting conditions of multiplication facts
      retrieval in a number-matching task (LeFevre, Bisanz, & Mrkonjic, 1988). By
      presenting two digits as cue and by requiring participants to decide whether a
      subsequent numerical target had been present in the pair, we found interference
      when the target coincided with the product of the cue digits. This was evidence
      for obligatory activation of multiplication facts. Also, we showed that
      multiplication facts retrieval occurred even in the absence of any arithmetic
      context (i.e., a multiplication sign between the cue digits) and did not require
      processing resources (i.e., the process met the capacity criterion of
      automaticity; Jonides, 1981), whereas manipulation of the spatial relation
      between the two operands (cue digits) negatively affected retrieval. The present
      work appears to be unique in the context of previous similar studies on mental
      calculation, which invariably adopted an arithmetic task as the primary demand.
      We identify this difference as the reason for the failure of all previous studies
      in revealing independence of multiplication facts from attentional resources.
      Furthermore, we suggest the application of a contextual definition of
      automaticity to this kind of retrieval, given the fact that it might depend both
      on association strength and on contextual setting variables.

PMID- 15513257
TI  - Failure of a landmark to restrict spatial learning based on the shape of the
      environment.
AB  - Rats were required to find a submerged platform in the corner of a swimming pool
      with a distinctive shape. A landmark near the platform did not interfere with the
      control acquired by the pool's shape over searching for the platform. This
      outcome was observed with an overshadowing and a blocking design. A comparison of
      the ease with which the landmark and the pool's shape gained control over
      searching for the platform indicates that the failure of overshadowing and
      blocking was not a consequence of the landmark being less salient than the shape
      of the pool. The results are not readily explained by theories of associative
      learning, but they are consistent with the claim that learning about the shape of
      the environment takes place in a dedicated module, which excludes information
      about the significance of individual landmarks.

PMID- 15513258
TI  - Asymmetry of generalization decrement in causal learning.
AB  - Two experiments required volunteers to learn which of various "planes" caused
      high levels of pollution. Novel test items were then rated as causes of
      pollution. Items created by adding novel features were rated at the same level as
      that of the original training items but items created by removing features
      received reduced ratings. This asymmetry of generalization decrement was not
      predicted by a well-known configural model of stimulus representation (Pearce,
      1987, 1994) but was predicted by a recently proposed model of stimulus
      representation, the replaced-elements model (Brandon, Vogel, & Wagner, 2000).

PMID- 15513259
TI  - Retrospective revaluation effects in the conditioned suppression procedure.
AB  - In four experiments using the conditioned suppression procedure, rats received
      initial reinforced training with two compound stimuli, AX and BY, each compound
      consisting of one auditory and one visual element. After a second phase of
      training consisting of nonreinforced presentations of A, the suppression governed
      by X and Y was tested. In Experiment 1 X evoked slightly less suppression than Y
      (a mediated extinction effect). This outcome was obtained when the auditory cues
      served as X and Y(Experiment 1a), when the visual cues served as X and
      Y(Experiment 1b), and when the number of nonreinforced presentations of A was
      increased (Experiment 1c) from 18 to 216. In Experiment 2, however, in which the
      initial training was given with serial compounds (i.e., A --> X and B --> Y) X
      evoked more suppression than Y (a recovery-from-overshadowing effect). It was
      argued that extinction of A engages two learning processes, one increasing the
      effective associative strength of its associate (X) and one reducing it, and that
      the balance between these two depends on the specific conditions of training.

PMID- 15513260
TI  - Backward blocking in honeybees.
AB  - Three experiments with foraging honeybees were designed to study the effect of
      experience with A on responding to B after AB+ training. In the first experiment,
      responding to B was the same whether the AB+ training was preceded or followed by
      A+ training. In the second experiment, responding to B after AB+ training was
      less in animals that also had A+ training than in control animals that were
      equally often reinforced in the absence of A; whether the A+ training preceded,
      was concurrent with, or followed the AB+ training made no difference. In the
      third experiment, responding to B after AB+ training was less when the AB+
      training was followed by A+C- training than when it was followed by C+/A-
      training. These results, like those of some recent vertebrate experiments, take
      us beyond the traditional explanation of blocking in terms of impaired
      conditioning of B on AB+ trials and support the suggestion that the mechanism,
      still poorly understood, may nevertheless be a relatively simple one.

PMID- 15513261
TI  - Outcome additivity, elemental processing and blocking in human causality
      judgements.
AB  - Informing participants in a causal judgement task that outcomes are additive can
      increase blocking effects (Experiment 1). Outcome additivity information
      emphasizes the fact that the outcome following a compound is the sum of the
      effects of its elements. We suggest that the effect of providing outcome
      additivity information is to encourage elemental processing and thereby enhance
      blocking. Experiment 2 showed that blocking could be enhanced by factors
      encouraging elemental processing, and Experiment 3 demonstrated that blocking was
      reduced by manipulating the visual presentation of cues to encourage configural
      processing. While these experiments do not rule out the role of inference in
      causal judgement tasks, the results are most parsimoniously explained by
      associative accounts that allow flexibility in the encoding of compound cues.

PMID- 15513263
TI  - No association of the dopamine D4 receptor (DRD4) and -521 C/T promoter
      polymorphisms with infant attachment disorganization.
AB  - In a first molecular genetic study Lakatos and colleagues found an association
      between attachment disorganization and the dopamine D4 receptor (DRD4) gene
      polymorphism, in particular in the presence of the -521 T allele in the promoter
      region of the DRD4 gene. Replication of their study in a sample of 132 infants
      did not confirm the role of the DRD4 7+ -allele and the -521C/T promoter gene in
      disorganized attachment. Although our sample was larger, and contained more
      children with CT or TT alleles, which enhanced the probability of finding the
      DRD4 and C/T interaction, the association was not found. Even when we combined
      our sample with the Lakatos sample, the interaction effect of the DRD4 and -521
      C/T polymorphisms on disorganized attachment was absent.

PMID- 15513265
TI  - Naive observers' perceptions of family drawings by 7-year-olds with disorganized
      attachment histories.
AB  - Previous research has succeeded in distinguishing among drawings made by children
      with histories of organized attachment relationships (secure, avoidant, and
      resistant); however, drawings of children with histories of disorganized
      attachment have yet to be systematically investigated. The purpose of this study
      was to determine whether naive observers would respond differentially to family
      drawings of 7-year-olds who were classified in infancy as disorganized vs.
      organized. Seventy-three undergraduate students from one university and 78 from a
      second viewed 50 family drawings of 7-year-olds (25 by children with organized
      infant attachment and 25 by children with disorganized infant attachment).
      Participants were asked to (1) circle the emotion that best described their
      reaction to the drawings and (2) rate the drawings on 6 bipolar scales. Drawings
      from children classified as disorganized in infancy evoked positive emotion
      labels less often and negative emotion labels more often than those children
      classified as organized. Furthermore, drawings from children classified as
      disorganized in infancy received higher ratings on scales for disorganization,
      carelessness, family chaos, bizarreness, uneasiness, and dysfunction. These data
      indicate that naive observers are relatively successful in distinguishing
      selected features of drawings by children with histories of disorganized vs.
      organized attachment.

PMID- 15513266
TI  - An investigation into the possible overlap between PTSD and unresolved responses
      following stillbirth: an absence of linkage with only unresolved status
      predicting infant disorganization.
AB  - It has been suggested that the characteristic lapses in thinking and reasoning of
      the unresolved/disorganized (U) state of mind following traumatic loss involve
      psychological mechanisms similar to those found in PTSD and that a fuller
      understanding of these mechanisms may help explain the disruptions in parental
      caretaking behaviour that lead to disorganized infant attachment. This paper
      investigates whether PTSD, assessed in 60 mothers in the pregnancy after
      stillbirth, predicts infant disorganized (D) attachment in next-born children,
      and whether there was any association between U and PTSD. We report that in this
      population there was no significant correspondence between U and PTSD scores or
      caseness and no association between maternal PTSD and infant D. We discuss
      possible interpretations of these findings.

PMID- 15513268
TI  - An attachment-based treatment of maltreated children and young people.
AB  - Repetitive, intrafamilial abuse and neglect leads to a complex array of
      deficiencies and symptoms that reflect both the traumatic effects of maltreatment
      on children as well as the effects of their failing to develop a coherent pattern
      of attachment behaviours toward their caregivers. This article will attempt to
      describe principles of a psychological treatment for maltreated children and
      young people who have been placed in foster care and adoptive homes. This
      treatment, based on attachment theory, provides dyadic interventions that aim to
      be transforming and integrative. The co-regulation of affect and the co
      construction of meaning are central to the treatment process, just as they are
      central features in attachment security.

PMID- 15513269
TI  - Reflections on 'an attachment-based treatment of maltreated children and young
      people'.
AB  - This paper considers the work of a skilled clinician (see this volume) who uses
      attachment theory but also his own vast body of experience. Many of the ideas
      will be of considerable help particularly to those working with children in
      substitute families. Caution is needed, however, as this work often involves the
      uncovering of unexpected abuse experiences which can provoke intense reactions.
      Training and supervision would seem essential.

PMID- 15513270
TI  - Adult attachment style and interpersonal distance.
AB  - We tested for an association between adults' attachment style and their
      regulation of interpersonal physical distance. In Study 1, the stop-distance
      paradigm was used to derive measures reflecting tolerance of and reactiveness to
      spatial-intrusion. As predicted, university students who were classified as
      avoidantly attached (by a 3-category attachment style measure) were less tolerant
      of close interpersonal physical proximity than were securely attached
      individuals. Further, they were more reactive to spatial-intrusion by a male (but
      not a female) adult. In Study 2, we measured the distance that participants chose
      to sit from an interviewer. Participants' ratings on a 4-category measure were
      used to classify them into an attachment style and to derive measures of positive
      self model and positive other model. Results revealed that fearfully avoidant
      adults were distinguished by their choice of far interpersonal distances. Across
      subjects, the measure of positive self model made a unique contribution to choice
      of interpersonal distance, but the measure of positive other model did not. In
      summary, the data provide evidence of an association between adults' comfort with
      interpersonal emotional closeness (attachment style) and their comfort with and
      regulation of interpersonal physical closeness.

PMID- 15513271
TI  - Associations between parental and child attachment representations.
AB  - In the present article on intergenerational transmission of attachment
      representations, we use mothers' and fathers' Adult Attachment Interview
      classifications to predict a 3-year-old's responses to the Attachment Story
      Completion Task (ASCT). We present a Q-sort coding procedure for the ASCT, which
      was developed for children as young as three. The Q-sort yields scores on four
      attachment dimensions (security, deactivation, hyperactivation, and
      disorganization). One-way ANOVAs revealed significant mother-child associations
      for each dimension, although results for the hyperactivation and disorganization
      dimensions were significant only according to contrast tests. Conversely, no
      father-child association was found, regardless of the dimension considered.
      Findings are discussed in terms of the respective part played by each parent in
      their children's emotional development.

PMID- 15513272
TI  - Social information processing in middle childhood: relations to infant-mother
      attachment.
AB  - This longitudinal study was designed to examine the links between infant-mother
      attachment and social information processing in middle childhood. The Strange
      Situation was used to assess infant-mother attachment at 12 months and a revised
      and adapted Hebrew version of the Social Information Processing Interview (Dodge
      & Price, 1994) was used to measure social information processing in middle
      childhood (at 7.5 years). Findings revealed that with regard to both peer-group
      relationships and mother-child relationships, secure children demonstrated more
      competent social information processing than insecure-ambivalent children in one
      out of four social information processing stages. The major characteristic
      distinguishing secure from insecure-ambivalent children's social information
      processing was their level of expectations from others: secure children expected
      others to be emotionally and instrumentally available to them (but in the case of
      peers--only if their own behavior was socially acceptable), whereas ambivalent
      children did not expect others to be available to them in both peer-group and
      mother-child circumstances.

PMID- 15513273
TI  - The dangers of reporting spurious regression to the mean.

PMID- 15513274
TI  - Confirmatory factor analysis of the Test of Performance Strategies (TOPS) among
      adolescent athletes.
AB  - The aim of the present study was to examine the factorial validity of the Test of
      Performance Strategies (TOPS; Thomas et al., 1999) among adolescent athletes
      using confirmatory factor analysis. The TOPS was designed to assess eight
      psychological strategies used in competition (i.e. activation, automaticity,
      emotional control, goal-setting, imagery, negative thinking, relaxation and self
      talk,) and eight used in practice (the same strategies except negative thinking
      is replaced by attentional control). National-level athletes (n = 584) completed
      the 64-item TOPS during training camps. Fit indices provided partial support for
      the overall measurement model for the competition items (robust comparative fit
      index = 0.92, Tucker-Lewis index = 0.88, root mean square error of approximation
      = 0.05) but minimal support for the training items (robust comparative fit index
      = 0.86, Tucker-Lewis index = 0.81, root mean square error of approximation =
      0.06). For the competition items, the automaticity, goal-setting, relaxation and
      self-talk scales showed good fit, whereas the activation, emotional control,
      imagery and negative thinking scales did not. For the practice items, the
      attentional control, emotional control, goal-setting, imagery and self-talk
      scales showed good fit, whereas the activation, automaticity and relaxation
      scales did not. Overall, it appears that the factorial validity of the TOPS for
      use with adolescents is questionable at present and further development is
      required.

PMID- 15513275
TI  - Knowledge and perceptions of sport psychology within English soccer.
AB  - The aim of the present study was to examine knowledge and perceptions of applied
      sport psychology within English soccer. National coaches (n = 8), youth academy
      directors (n = 21) and academy coaches (n = 27) were surveyed using questionnaire
      and interview methods. Questionnaire results revealed a lack of knowledge of
      sport psychology that appeared to underpin some of the most significant barriers
      to entry for sport psychologists. These included lack of clarity concerning the
      services of a sport psychologist, problems fitting in and players' negative
      perceptions of sport psychology. Overall, however, lack of finance was the
      highest rated barrier. Six barrier dimensions emerged from the interview data:
      negative perceptions of psychology, lack of sport psychology knowledge,
      integrating with players and coaching staff, role and service clarity, practical
      constraints, and perceived value of sport psychology. These findings were broadly
      compatible with the survey data, with finance emerging as a major barrier and
      misconceptions of sport psychology being common. Our conclusions are discussed in
      relation to the practical implications of the study for both applied research and
      the provision of sport psychology services within English soccer.

PMID- 15513276
TI  - Protection against muscle damage in competitive sports players: the effect of the
      immunomodulator AM3.
AB  - Strenuous physical exercise of the limb muscles commonly results in damage,
      especially when that exercise is intense, prolonged and includes eccentric
      contractions. Many factors contribute to exercise-induced muscle injury and the
      mechanism is likely to differ with the type of exercise. Competitive sports
      players are highly susceptible to this type of injury. AM3 is an orally
      administered immunomodulator that reduces the synthesis of proinflammatory
      cytokines and normalizes defective cellular immune fractions. The ability of AM3
      to prevent chronic muscle injury following strenuous exercise characterized by
      eccentric muscle contraction was evaluated in a double-blind and randomized pilot
      study. Fourteen professional male volleyball players from the First Division of
      the Spanish Volleyball League volunteered to take part. The participants were
      randomized to receive either placebo (n=7) or AM3 (n=7). The physical
      characteristics (mean+/-s) of the placebo group were as follows: age 25.7+/-2.1
      years, body mass 87.2+/-4.1 kg, height 1.89+/-0.07 m, maximal oxygen uptake
      65.3+/-4.2 ml.kg(-1).min(-1). Those of the AM3 group were as follows: age 26.1+/
      1.9 years, body mass 85.8+/-6.1 kg, height 1.91+/-0.07 m, maximal oxygen uptake
      64.6+/-4.5 ml.kg(-1).min(-1). All participants were evaluated for biochemical
      indices of muscle damage, including concentrations of aspartate aminotransferase,
      alanine aminotransferase, alkaline phosphatase, creatine kinase (CK) and its MB
      fraction (CK-MB), myoglobin, lactate dehydrogenase, urea, creatinine and gamma
      glutamyltranspeptidase, both before and 30 days after treatment (over the peak of
      the competitive season). In the placebo group, competitive exercise (i.e.
      volleyball) was accompanied by significant increases in creatine kinase (494+/-51
      to 560+/-53 IU.l(-1), P < 0.05) and myoglobin (76.8+/-2.9 to 83.9+/-3.1 microg.l(
      1), P < 0.05); aspartate aminotransferase (30.8+/-3.0 to 31.1+/-2.9 IU.l(-1)) and
      lactate dehydrogenase (380+/-31 to 376+/-29 IU.l(-1)) were relatively unchanged
      after the 30 days maximum effort. AM3 not only inhibited these changes, it led to
      a decrease from baseline serum concentrations of creatine kinase (503+/-49 to
      316+/-37 IU.l(-1), P < 0.05) and myoglobin (80.1+/-3.2 to 44.1+/-2.6 IU.l(-1), P
      < 0.05), as well as aspartate aminotransferase (31.1+/-3.3 to 26.1+/-2.7 IU.l(
      1), P < 0.05) and lactate dehydrogenase (368+/-34 to 310+/-3 IU.l(-1), P < 0.05).
      The concentration of CK-MB was also significantly decreased from baseline with
      AM3 treatment (11.6+/-1.2 to 5.0+/-0.7 IU.l(-1), P < 0.05), but not with placebo
      (11.4+/-1.1 to 10.8+/-1.4 IU.l(-1)). In conclusion, the use of immunomodulators,
      such as AM3, by elite sportspersons during competition significantly reduces
      serum concentrations of proteins associated with muscle damage.

PMID- 15513277
TI  - Comparison of the men's and the women's pole vault at the 2000 Sydney Olympic
      Games.
AB  - The aim of this study was to identify differences between elite male and female
      pole vaulters in terms of their mechanical energy and angular momentum. The
      vaulter's total mechanical energy and angular momentum were calculated from the
      three-dimensional kinematic data of the pole vault finals at the Sydney 2000
      Olympic Games. The development of total, kinetic and potential energy showed
      similar characteristics for men and women. The initial energy of the vault, the
      energy at maximum pole bend position and the final energy were significantly
      higher for male athletes (P <0.05), while the energy gain produced by the
      athletes during the vault showed no significant differences (male vaulters 5.88
      +/- 1.02 J.kg(-1), female vaulters 5.74 +/- 1.63 J.kg(-1)). Time-related
      parameters relating to pole bending and recoiling also showed no significant
      differences (P <0.05). In contrast to the male vaulters, the female vaulters did
      not show a free upward flight phase. The angular momentum was significantly
      higher for the female vaulters during the initial pole bend and during the bar
      clearance (P <0.05). We conclude that the pole vaulting technique of female elite
      athletes is not a projection of the technique of male elite vaulters at a lower
      jump height, but rather a different way of jumping and interacting with the
      elastic pole. The current technique of elite female pole vaulters still has
      potential for further improvement.

PMID- 15513278
TI  - Time-motion analysis of elite field hockey, with special reference to repeated
      sprint activity.
AB  - Limited information exists about the movement patterns of field-hockey players,
      especially during elite competition. Time-motion analysis was used to document
      the movement patterns during an international field-hockey game. In addition, the
      movement patterns of repeated-sprint activity were investigated, as repeated
      sprint ability is considered to be an important fitness component of team-sport
      performance. Fourteen members of the Australian men's field-hockey team (age 26+/
      3 years, body mass 76.7+/-5.6 kg, VO2max 57.9+/-3.6 ml.kg(-1).min(-1); mean+/-s)
      were filmed during an international game and their movement patterns were
      analysed. The majority of the total player game time was spent in the low
      intensity motions of walking, jogging and standing (46.5+/-8.1, 40.5+/-7.0 and
      7.4+/-0.9%, respectively). In comparison, the proportions of time spent in
      striding and sprinting were 4.1+/-1.1 and 1.5+/-0.6%, respectively. Our criteria
      for 'repeated-sprint' activity (defined as a minimum of three sprints, with mean
      recovery duration between sprints of less than 21 s) was met on 17 occasions
      during the game (total for all players), with a mean 4+/-1 sprints per bout. On
      average, 95% of the recovery during the repeated-sprint bouts was of an active
      nature. In summary, the results suggest that the motion activities of an elite
      field-hockey competition are similar to those of elite soccer, rugby and
      Australian Rules football. In addition, the investigation of repeated-sprint
      activity during competition has provided additional information about the unique
      physiological demands of elite field-hockey performance.

PMID- 15513279
TI  - The creatine content of Creatine Serum and the change in the plasma concentration
      with ingestion of a single dose.
AB  - Three samples of Creatine Serum ATP Advantage from Muscle Marketing USA, Inc.
      were assayed for creatine by two different techniques by four independent
      laboratories, and for creatinine by two different techniques by two laboratories.
      A further sample was assayed for phosphorylcreatine. Dry weight and total
      nitrogen were also analysed. Six male volunteers ingested in random order, over 3
      weeks: (A) water; (B) 2.5 g creatine monohydrate (Cr.H2O) in solution; and (C) 5
      ml Creatine Serum (reportedly containing an equivalent amount of Cr.H2O). Blood
      samples were collected before and up to 8 h after each treatment and plasma was
      analysed for creatine and creatinine. Eight-hour urine samples were analysed for
      creatine. Ingestion of 2.5 g creatine monohydrate in solution resulted in a
      significant increase in plasma creatine (from 59.1+/-11.8 micromol.l(-1) to
      245.3+/-74.6 microM micromol.l(-1); mean+/-s) and urinary creatine excretion. No
      increase in plasma or urinary creatine or creatinine was found on ingestion of
      Creatine Serum or water. Analysis showed 5 ml of Creatine Serum to contain <10 mg
      Cr.H2O and approximately 90 mg creatinine. Phosphorylcreatine was not detectable
      and only a trace amount of phosphorous was present. Total nitrogen analysis ruled
      out significant amounts of other forms of creatine. We conclude that the trace
      amounts of creatine in the product would be too little to affect the muscle
      content even with multiple dosing.

PMID- 15513280
TI  - Concentric left ventricular morphology in aerobically trained kayak canoeists.
AB  - The aim of the present study was to test the hypothesis that upper body
      aerobically trained athletes (kayak canoeists) would have greater left
      ventricular wall thickness, but similar left ventricular diastolic chamber
      dimensions, compared with recreationally active and sedentary men. Ultrasound
      echocardiography was used to determine cardiac structure and function in highly
      trained kayak canoeists (n = 10), moderately active (n = 10) and sedentary men (n
      = 10). The septal and posterior left ventricular walls were approximately 0.2 cm
      thicker in kayak canoeists (P < 0.05), and left ventricular mass was 51% and 32%
      greater (P < 0.05) in canoeists than in the sedentary and moderately trained
      participants, respectively. There were no differences in left ventricular chamber
      dimension, suggesting that the kayak canoeists had a concentric pattern of left
      ventricular adaptation to aerobic upper body training. Scaling the data to body
      composition indices had no effect on the outcome of the statistical analysis.
      There were no differences in resting Doppler left ventricular diastolic or
      systolic function among the groups. Ejection fraction was lower in the kayak
      canoeists, but the magnitude of the difference was within the normal variability
      for this measurement. Thus aerobically upper body trained athletes demonstrated a
      concentric pattern of cardiac enlargement, but resting left ventricle function
      was not different between athletes, moderately active and sedentary individuals.

PMID- 15513281
TI  - Influence of a stressing constraint on stiffness and damping functions of a ski
      simulator's platform motion.
AB  - The aim of this study was to assess the effect of stress on a previously acquired
      motor coordination. Following a longitudinal learning experiment, four
      participants performed oscillations on a ski simulator, either in normal or
      stressful conditions. The results showed that the amplitude of the oscillations
      decreased under stress, but no significant effect was seen regarding
      coordination, suggesting the strong resistance to stress of overlearned
      behaviour. Nevertheless, for one participant, a transient regression towards a
      former stage of learning was observed. This result was consistent with the
      regression hypothesis formulated by Fuchs (1962).

PMID- 15513282
TI  - Effects of physical activities that induce moderate external loading on bone
      metabolism in male athletes.
AB  - Sports characterized by little or moderate weight bearing or impact have a low
      osteogenic effect. However, the action of such sports on bone turnover remains
      unclear. The objective of this study was to determine the effect on bone
      remodelling of physical activities that induce moderate external loading on the
      skeleton. Thirty-eight male athletes aged 18-39 years (cyclists, n = 11;
      swimmers, n = 13; triathletes, n = 14) and 10 age-matched sedentary controls aged
      22-35 years participated in the study. The study combined measurement of bone
      mineral density by dual-energy X-ray absorptiometry and bone turnover assessment
      from specific biochemical markers: serum bone-specific alkaline phosphatase,
      osteocalcin, urinary type I collagen C-telopeptide and calcium. Compared with the
      controls and swimmers, adjusted bone mineral density was higher (P < 0.05) in
      triathletes at the total proximal femur and lower limbs. No differences in bone
      mineral density were found between cyclists, swimmers and controls. Compared with
      controls, osteocalcin was higher (P < 0.05) in triathletes and swimmers and
      urinary type I collagen C-telopeptide was higher in swimmers only. Serum bone
      specific alkaline phosphatase was lower (P < 0.05) in cyclists than in all other
      groups. In conclusion, an osteogenic effect was found only in triathletes, mainly
      at bone sites under high mechanical stress. Bone turnover differed in athletes
      compared with controls, suggesting that bone turnover may be sport-practice
      dependent. Despite some encouraging observations, it was not possible to show
      that changes in the bone remodelling process were sport-discipline dependent.

PMID- 15513283
TI  - Height, frailty, and the standard of living: modelling the effects of diet and
      disease on declining mortality and increasing height.
AB  - Explanations of historical trends in both mortality and human height differ over
      the relative contributions of better nutrition and reduced exposure to disease.
      This paper explores theoretical models in which interactions between diet and
      disease determine both mortality and height. One model assumes that adult height
      is directly related to frailty, the relative risk of dying. The second model
      links frailty to differences between attained and potential height. Diet plays a
      small role in the transition to low mortality in the first model. The second
      model assigns a large role to diet in historical mortality trends, but implies
      that mortality will be unrelated to height in the future.

PMID- 15513284
TI  - China's missing children: the 2000 census underreporting surprise.
AB  - We compare the age and sex structure of China's 2000 population census to an
      estimate of that structure derived from a projection from the 1990 census. Based
      on China's own official estimates of demographic change, our intercensal analysis
      indicates a shortfall in enumeration of more than a quarter of all children under
      age 5 and an eighth of those between 5 and 9, a total of nearly 37 million
      children missing in the 2000 census. We show that the shortfall is primarily due
      to underreporting of children in the census. Sex differences in child
      underreporting were fairly minor. Child underreporting in China is not
      unprecedented, but child underreporting rates in 2000 were about triple those of
      previous censuses. We attribute the increase primarily to policy changes
      beginning in the early 1990s that held officials at all jurisdictional levels
      personally responsible for enforcing birth quotas.

PMID- 15513285
TI  - Long-term effects of childbearing on mortality: evidence from pre-industrial
      Sweden.
AB  - This paper presents an analysis of the impact of childbearing history on later
      life mortality for ever-married men and women using historical micro-level data
      of high quality for southern Sweden. The analysis uses a Cox proportional hazards
      model, estimating the effects on old-age mortality of number of births and timing
      of first and last births. By studying the effects of previous childbearing on
      mortality by sex and social status, we also gain important insights into the
      mechanisms relating childbearing to mortality in old age. The results show that
      number of children ever born had a statistically significant negative impact on
      longevity after age 50 for females but not for males. Analysis by social group
      shows that only landless women experienced higher mortality from having more
      children, which seems to indicate that the main explanations are to be found in
      social or economic conditions specific to females, rather than in the strictly
      biological or physiological effects of childbearing.

PMID- 15513286
TI  - The peculiar pattern of mortality of Jews in Moscow, 1993-95.
AB  - Russian Jews, particularly men, have a large mortality advantage compared with
      the general Russian population. We consider possible explanations for this
      advantage using data on 445,000 deaths in Moscow, 1993-95. Log-linear analysis of
      the distribution of deaths by sex, age, ethnic group, and cause of death reveals
      a relatively high concentration of endogenous causes and a relatively low
      concentration of exogenous and behaviourally induced causes among Jews. There is
      also a significant concentration of deaths from breast cancer among Jewish women.
      Mortality estimates using the 1994 micro-census population as the denominator
      reveal an 11-year Russian-Jewish gap in the life expectancy of males at age 20,
      but only a 2-year life-expectancy gap for women. Only 40 per cent of the Russian
      Jewish difference for men, but the entire difference for women, can be eliminated
      by adjustment for educational differences between the two ethnic groups.
      Similarities with other Jewish populations and possible explanations are
      discussed.

PMID- 15513287
TI  - Estimating the stability of census-based racial/ethnic classifications: the case
      of Brazil.
AB  - This study presents a method of estimating the degree to which people change
      their racial/ethnic identity from one census enumeration to another. The
      technique is applied to the classification of skin colour in Brazil (white,
      black, brown, yellow). For the period 1950-80, the findings show a deficit of 38
      per cent in the black category and a gain of 34 per cent in the brown category,
      suggesting that a large proportion of individuals who declared themselves black
      in 1950 reclassified themselves as brown in 1980. Estimates for 1980-90, adjusted
      for the effects of international migration, reveal a similar pattern, although
      the magnitude of colour reclassification may have declined somewhat during the
      1980s. Procedures to determine the stability of racial/ethnic identity produce
      data useful to recent policy initiatives that rely on demographic censuses to
      measure changes in the status of minority groups in less developed countries.

PMID- 15513288
TI  - Maternal resources, proximity of services, and curative care of boys and girls in
      Minya, Egypt 1995-97.
AB  - Despite declines in the risk of dying among children in Egypt, girls' excess
      mortality in early childhood persists. Using data from a representative sample of
      children in Minya, Egypt, I assess whether maternal resources, marital household
      structure, and proximity of services influence disparities by sex in curative
      care. The results show that boys visit any source of care marginally more often
      than girls. Among children who receive care, boys more often receive private
      care. Higher maternal education has no effect on the relative odds of private
      care, whereas maternal residence with marital relatives reduces the odds that
      girls receive private care. Having a public clinic in the neighbourhood, at which
      private services may be offered, increases girls' odds of receiving private care.
      Higher and more equitable levels of care-seeking at public and private services
      of higher quality may reduce differences in the survival of boys and girls in a
      highly sex-stratified setting.

PMID- 15513289
TI  - Popular perceptions of emerging influences on mortality and longevity in
      Bangladesh and West Bengal.
AB  - Relatively little is known about how environmental and pathological threats to
      human survival and longevity are perceived by the public. In this study in rural
      Bangladesh and West Bengal, India, which used individual interviews and focus
      group discussions to investigate the changing costs of and motivations for
      reproduction, respondents were questioned about their perceptions of changes in
      mortality. The findings show that, while child mortality levels are perceived to
      have fallen dramatically in recent times, the health and survival prospects of
      the middle aged and the elderly are seen to have been better in the past. The
      perceived decline in adult health is attributed to environmental deterioration
      and lifestyle changes accompanying modernization. This paper explores people's
      reasons for this unexpected worldview. References to pesticides and chemical
      fertilizers as causes of death abound in their explanations and are seen to be
      associated with unhealthy agricultural practices and impiety.

PMID- 15513292
TI  - Postmenopausal hormone therapy before and after the women's health initiative
      study: what consequences?
AB  - This review focuses on the question of whether the Women's Health Initiative
      (WHI) was a test of primary versus secondary cardiovascular benefits of
      postmenopausal hormone therapy. Evidence is presented to support the conclusion
      that the WHI was a secondary intervention trial and that primary cardiovascular
      benefits of hormone therapy are rational, likely, but not yet proven. The review
      makes clear that hormone therapy is not a 'cardiovascular drug' for the treatment
      of coronary heart disease; but rather that the public health debate is whether
      hormone therapy, used for the treatment of menopausal symptoms, provides any
      cardiovascular benefits that might offset its risk.

PMID- 15513293
TI  - Prolactin and the prolactin receptor: new targets of an old hormone.
AB  - Prolactin (PRL) is one of a family of related hormones including growth hormone
      (GH) and placental lactogen (PL) that are hypothesized to have arisen from a
      common ancestral gene about 500 million years ago. Over 300 different functions
      of PRL have been reported, highlighting the importance of this pituitary hormone.
      PRL is also synthesized by a number of extra-pituitary tissues including the
      mammary gland and the uterus. Most of PRL's actions are mediated by the
      unmodified 23 kDa peptide, however, PRL may be modified post-translation, thereby
      altering its biological effects. PRL exerts these effects by binding to its
      receptor, a member of the class I cytokine receptor super-family. This activates
      a number of signaling pathways resulting in the transcription of genes necessary
      for the tissue specific changes induced by PRL. Mouse knockout models of the
      major forms of the PRL receptor have confirmed the importance of PRLs role in
      reproduction. Further knockout models have provided insight into the importance
      of PRL signaling intermediates and the advent of transcript profiling has allowed
      the elucidation of a number of PRL target genes.

PMID- 15513294
TI  - Insulin resistance in patients with polycystic ovary syndrome.
AB  - With a prevalence of 5%-10% the polycystic ovary syndrome (PCOS) is an
      exceptionally common disorder of premenopausal women. According to prospective
      studies, women with PCOS present abnormal glucose tolerance and diabetes mellitus
      in 31%-35% and 7.5%-10%, respectively. PCOS patients have a higher prevalence of
      cardiovascular risk factors such as hypertension, type 2 diabetes and
      dyslipidaemia. The rate of spontaneous abortions as well as the risk to develop
      gestational or type 2 diabetes is increased in PCOS. Therefore, PCOS is not only
      a reproductive problem but a complex endocrine disease with important health
      implications. The role of the glucose metabolism in PCOS, the health consequences
      and possible interventions are reviewed in this article.

PMID- 15513295
TI  - The contribution of hibernation to heart failure.
AB  - For many years the functional sequelae of chronic coronary artery disease (CAD)
      were considered irreversible. Evidence accrued over the past three decades proves
      that this concept is not necessarily true. Non-randomised studies demonstrated
      that coronary revascularisation (CR) confers symptomatic and prognostic benefits
      to patients with CAD and heart failure. Based on available studies, one can
      assume that the beneficial effect of CR in heart failure derives primarily from
      recovery of contractile function in 'hibernating myocardium' (HM), i.e.,
      chronically dysfunctional, but viable, myocardium subtended by stenosed coronary
      arteries which recovers after CR. Cardiac imaging with echocardiography, single
      photon and positron emission tomography (PET) and magnetic resonance allows the
      identification of HM. These techniques have comparable predictive values in
      patients with moderate left ventricular impairment. PET studies have shown that
      resting myocardial blood flow is preserved in most cases of HM while its main
      feature is a severe impairment of coronary flow reserve. Thus, the
      pathophysiology of HM is more complex than initially postulated. Recent evidence
      that repetitive ischaemia in patients can be cumulative and lead to more severe
      and prolonged stunning, lends further support to the hypothesis that, at least
      initially, stunning and HM are two facets of the same coin.

PMID- 15513296
TI  - Heart rate variability estimates of autonomic tone: relationship to mapping
      pathological and procedural stress responses in coronary disease.
AB  - Many lines of experimental evidence suggest the interplay of the autonomic
      nervous system and a variety of mediators of vascular atheroma and ultimately
      vascular occlusion. In vivo study in human volunteers and patients is hampered by
      the lack of a reliable and sensitive marker of prevailing autonomic tone able to
      reflect the appropriate dynamic change in nervous activity. Currently, the modern
      standard for definition of autonomic tone is based on a variety of analyses of R
      R interval variability from the surface ECG. In this review, we consider whether
      heart rate variability techniques are sensitive enough to define relevant
      clinical interactions between neural tone and other mediators of vascular
      occlusion--specifically, mechanical pressure, thrombotic and hormonal factors-
      which are relevant to atherosclerotic vascular disease.

PMID- 15513297
TI  - The molecular genetics of migraine.
AB  - Within the past decade it has been possible to identify susceptibility gene loci
      that predispose to migraine using genetic markers distributed across the human
      genome. Five new loci with significant linkage to common types of migraine-
      migraine with or without aura--have been identified on four different chromosomes
      using a genome-wide screen approach. So far, only the locus on 4q has been
      replicated but no specific, disease-causing mutations have been described in
      these common forms of migraine. The best genetic evidence providing molecular
      insight into migraine still comes from the mutations detected in a rare Mendelian
      form of migraine with aura--familial hemiplegic migraine (FHM). In 50%-70% of FHM
      families, mutations in the calcium channel gene CACNA1A in chromosome 19p13 have
      been identified. In some families, mutations in the ATP1A2 gene encoding the
      alpha2 subunit of the Na+, K+-ATPase are associated with FHM, linked to 1q23.
      Here we discuss the current knowledge of the heritability of migraine and rare
      migraine variants as models for understanding the pathophysiology of common
      migraine and animal models that might contribute to understanding common forms of
      migraine.

PMID- 15513298
TI  - Fatality of myocardial infarction in relation to the coronary anatomy: role of
      culprit lesion location.
AB  - OBJECTIVE: We set out to study the effect of the location of the culprit coronary
      lesion on myocardial infarction (MI) fatality by combining data from MI survivors
      in the coronary care unit (CCU) and autopsied patients with pre-hospital fatal
      MI. DESIGN: We studied two simultaneous series of men under 70 years with fatal
      pre-hospital MI (n = 36) and men admitted for acute ST-elevation-MI (n = 92). The
      culprit lesion was identified by the presence of thrombus at autopsy and by
      coronary angiography in patients admitted to the CCU. RESULTS: The culprit lesion
      was located in the right coronary artery (RCA) in 22 (61%) of 36 men with fatal
      MI compared to 30 (33%) of 92 men with non-fatal MI (P = 0.01). Seventy-three
      percent of fatal RCA occlusions were proximal as opposed to only 30% of non-fatal
      RCA occlusions (P < 0.001). Forty-four percent of all fatal MI were due to
      proximal RCA occlusion as opposed to only 10% of non-fatal MI (P < 0.005).
      CONCLUSIONS: Proximal RCA occlusions were very often found among men with fatal
      pre-hospital MI, whereas left-sided coronary occlusions were significantly more
      frequent in hospital-admitted survivors of MI. Left-sided coronary occlusions may
      be associated with a more favourable pre-hospital phase of acute MI compared to
      proximal RCA occlusions.

PMID- 15513299
TI  - The enterohepatic nuclear receptors are major regulators of the enterohepatic
      circulation of bile salts.
AB  - Recent studies have established that bile salts are signaling molecules, besides
      their classic function in dietary lipid absorption and cholesterol metabolism.
      Bile salts signal by activating mitogen-activated protein kinase (MAPK) pathways
      and nuclear receptors like farnesoid X receptor-alpha (FXRalpha). FXRalpha
      activation increases the expression of direct FXRalpha target genes involved in
      bile salt transport and detoxification, and decreases expression of indirect
      FXRalpha target genes involved in bile salt biosynthesis and uptake. These
      actions prevent toxic accumulation of bile salts in the enterohepatic organs. A
      network of interactions with other nuclear receptors and MAPK pathways may
      protect the liver against pathological elevation of bile salts and cholestasis.
      Therefore treatment of cholestasis might benefit from the development of FXRalpha
      agonists.

PMID- 15513300
TI  - Clinical and biological importance of cytogenetic abnormalities in childhood and
      adult acute lymphoblastic leukemia.
AB  - Among the approximately 7,000 cytogenetically abnormal childhood and adult B- and
      T-lineage acute lymphoblastic leukemias (ALL) published to date, numerous
      recurring chromosomal aberrations and abnormality patterns have been identified,
      and it has been clearly shown that the cytogenetic features often correlate
      closely with specific morphologic, immunophenotypic, and clinical parameters.
      Thus, karyotypic investigations are now routinely performed for diagnostic and
      prognostic purposes in ALL, with the chromosomal abnormalities/cytogenetic
      patterns playing a major role for proper risk assessment and choice of treatment.
      At the same time, the cytogenetic analyses have resulted in the identification of
      more than 70 different genes, located at the breakpoints of ALL-associated
      structural chromosomal abnormalities, that are causally implicated in the
      leukemogenic process. Hence, the genetic studies have also improved our
      understanding of the mechanisms of leukemogenesis. However, the almost staggering
      amount of cytogenetic information presently available has made it increasingly
      difficult to obtain a general overview of the clinical and biological importance
      of karyotypic patterns in ALL. Here, we summarize and review the cytogenetic
      features of childhood and adult ALL, with emphasis on their molecular genetic
      consequences and their clinical impact.

PMID- 15513301
TI  - Xenotransplantation and risks of zoonotic infections.
AB  - The shortage of human organs and tissues for transplantation and the advances in
      immunology of rejection and in genetic engineering have renewed interest in
      xenotransplantation--the transplantation of animal organs, tissues or cells to
      humans. Clinical trials have involved the use of non-human primate, porcine, and
      bovine cells/tissues/organs. In recent years, research has focused mainly on pigs
      as donors (especially, pigs genetically engineered to carry some human genes).
      One of the major concerns in xenotransplantation is the risk of transmission of
      animal pathogens, particularly viruses, to recipients and the possible adaptation
      of such pathogens for human-to-human transmission. Porcine endogenous
      retroviruses (PERVs) have been of special concern because of their ability to
      infect human cells and because, at present, they cannot be removed from the
      source animal's genome. To date, retrospective studies of humans exposed to live
      porcine cells/tissues have not found evidence of infection with PERV but more
      extensive research is needed. This article reviews infectious disease risks
      associated with xenotransplantation, some measures for minimizing that risk, and
      microbiological diagnostic methods that may be used in the follow-up of
      xenotransplant recipients.

PMID- 15513302
TI  - Cardiac cachexia.
AB  - Chronic heart failure (CHF) remains an important and increasing public health
      care problem. It is a complex syndrome affecting many body systems. Body wasting
      (i.e., cardiac cachexia) has long been recognised as a serious complication of
      CHF. Cardiac cachexia is associated with poor prognosis, independently of
      functional disease severity, age, and measures of exercise capacity and cardiac
      function. Patients with cardiac cachexia suffer from a general loss of fat
      tissue, lean tissue, and bone tissue. Cachectic CHF patients are weaker and
      fatigue earlier, which is due to both reduced skeletal muscle mass and impaired
      muscle quality. The pathophysiologic alterations leading to cardiac cachexia
      remain unclear, but there is increasing evidence that metabolic, neurohormonal
      and immune abnormalities may play an important role. Cachectic CHF patients show
      raised plasma levels of epinephrine, norepinephrine, and cortisol, and they show
      high plasma renin activity and increased plasma aldosterone level. Several
      studies have also shown that cardiac cachexia is linked to raised plasma levels
      of tumour necrosis factor alpha and other inflammatory cytokines. The degree of
      body wasting is strongly correlated with neurohormonal and immune abnormalities.
      The available evidence suggests that cardiac cachexia is a multifactorial
      neuroendocrine and metabolic disorder with a poor prognosis. A complex imbalance
      of different body systems may cause the development of body wasting.

PMID- 15513303
TI  - Hypoxia-inducible factors and hypoxic cell death in tumour physiology.
AB  - Hypoxic up-regulation of hypoxia-inducible factors (HIFs) during tumourigenesis
      presents an interesting paradox with respect to their role in tumour growth.
      Hypoxia-inducible factor 1 (HIF-1) plays a key role in the adaptive response to
      hypoxia, trans-activating many genes whose protein products are involved in
      pathways of angiogenesis, glucose metabolism and cell proliferation, thus
      facilitating tumour progression. However, it is also emerging that up-regulation
      of HIF-1 trans-activates anti-proliferative and pro-apoptotic genes (such as
      BNIP3, NIX and IGFBP3). This makes it unclear as to whether HIF-1 up-regulation
      provides a selective advantage or disadvantage to neoplastic progression under
      hypoxia. In addition, vagaries in the hypoxic microenvironment of the tumour such
      as pH changes, presence of reactive oxygen species and energy availability in the
      form of adenosine triphosphate (ATP), appear to influence the function of HIF-1
      and up-regulated pathways and affect susceptibility to undergo hypoxic cell
      death. It is apparent that hypoxic cancer cells must be able to select against
      HIF-1 mediated cell death signals in order to survive and progress towards
      malignancy. Hypoxia-induced HIF-1 may in itself serve to select for increased
      malignancy by exerting pressure in the form of anti-proliferative signals that
      must be escaped. Understanding the mechanisms by which HIF-1 induces cell death
      and the manner in which the tumour cell can overcome such signals, is critical
      for our understanding of cancer progression and the development of effective
      therapeutics.

PMID- 15513304
TI  - Development of gene-specific double-stranded RNA drugs.
AB  - A relatively recent entrant into molecular biology--double-stranded RNA (dsRNA)-
      as a class exhibits a unique set of properties: relative stability, affinity for
      specific proteins and enzymes, ability to activate the interferon pathway and
      finally, RNA interference (RNAi). In RNAi, unique double-stranded short
      interfering RNA molecules (siRNA) destroy the corresponding target RNA with
      exquisite potency and selectivity, thus causing post-transcriptional gene
      silencing (PTGS). An understanding of the design of gene-specific dsRNA and
      development of techniques to deliver dsRNA in the cell and in live animals has
      heralded a new age of gene therapy without gene knockout. This review first
      summarizes the biological synthesis, metabolism and effect of the dsRNA with
      special emphasis on siRNA and RNAi. This is followed by the clinical,
      pharmacological and pharmaceutical prospects of the development of the dsRNA as a
      drug. It is clear that the dsRNA holds an enormous promise in the treatment of a
      large number of metabolic and infectious diseases including but not limited to
      cancer, macular degeneration, diabetic retinopathy, Alzheimer's and other neural
      disorders, autoimmune diseases, and all viral infections including AIDS (acquired
      immune deficiency syndrome), hepatitis and respiratory syncytial virus (RSV).

PMID- 15513305
TI  - Platelet morphology and plasma indices of platelet activation in essential
      hypertension: effects of amlodipine-based antihypertensive therapy.
AB  - BACKGROUND AND AIM: Platelet abnormalities have been described in hypertension,
      especially in the presence of target organ damage. Our aim was to study the
      differences in morphology and indices of platelet activation in treatment-naive
      patients with essential hypertension as compared to normotensive controls and
      secondly, to study the effects of amlodipine-based antihypertensive therapy on
      these indices. METHODS: We recruited 42 previously untreated, newly diagnosed
      hypertensive patients (25 men; mean age 53 years) for the cross-sectional study,
      where data were compared with those from 30 normotensive controls (20 men; mean
      age 57 years). Of the 42 untreated hypertensive patients who were recruited, 27
      patients successfully completed, the six-month treatment phase with amlodipine
      based antihypertensive therapy. Platelet morphology (volume and mass) was
      quantified, and plasma markers of platelet activation (betaTG and sPsel) measured
      in citrated plasma. The mass of P-selectin in each platelet (pPsel) was
      determined by lysing a fixed number of platelets and then determining the levels
      of P-selectin in the lysate. RESULTS: Hypertensive patients had significantly
      higher platelet volume (P = 0.01) and mass (P = 0.003), plasma betaTG and sPsel,
      and pPsel levels (all P < 0.001) compared to the controls. After a mean treatment
      time of 6 months, there was a decrease in platelet volume (P < 0.001) and mass (P
      = 0.02), with lower pPsel, sPsel and BTG levels (all P < 0.001) compared to the
      untreated state. CONCLUSION: Treatment of uncomplicated essential hypertension
      using amlodipine-based anti-hypertensive therapy results in a reversal of the
      platelet morphology abnormalities and indices of platelet activation. This may
      contribute to a reduction in thrombosis-related complications seen in those whose
      blood pressure lowering is effective.

PMID- 15513306
TI  - Endothelin in coronary artery disease.

PMID- 15513307
TI  - Cell transplantation for myocardial regeneration: hype or reality?

PMID- 15513317
TI  - Abnormal alkaline phosphatase isoenzymes detected in the serum of elderly
      patients.
AB  - Alkaline phosphatase (ALP) isoenzyme analysis of 101,832 serum samples was
      performed by electrophoresis using cellulose acetate membrane, and abnormal bands
      at the alpha(1) and alpha(2) globulin positions were detected in 23 samples. The
      physicochemical properties of these abnormal ALP isoenzyme fractions were
      examined. In brief, the abnormal fractions were heat-sensitive and inhibited by L
      phenylalanine, and neither sialic acid in their polysaccharide chains nor the
      glycosyl-phosphatidylinositol anchor was detected by the enzyme treatment. The
      physicochemical properties of abnormal ALP isoenzyme fractions detected in
      Patients 1 - 22 were similar to those of the adult small intestine type. However,
      the molecular weight of the adult small intestine type abnormal fractions was
      smaller than that of the normal fractions. These adult small intestine type
      abnormal bands at the alpha(1)- to alpha(2)-globulin positions, which were
      identified in the serum of Patients 1 - 22, were detected in elderly patients.
      Most of them had various basal diseases such as renal insufficiency, fracture,
      interstitial pneumonia, and chronic pancreatitis. Some of them had severe
      diseases such as rectal cancer, descending colon cancer, and septic shock. In
      Patient 23, the polysaccharide chain had sialic acid and was heat sensitive
      physicochemical properties that were similar to those of the Kasahara ALP
      variant.

PMID- 15513310
TI  - Isovolumetric relaxation time of the right ventricle assessed by tissue Doppler
      imaging.
AB  - OBJECTIVES: The isovolumetric relaxation time of the right ventricle (RV-IVRT)
      can be assessed using a method based on ECG and pulsed wave Doppler (PW).
      Recently pulsed wave Doppler tissue imaging (PW-DTI) has been introduced in the
      assessment. DESIGN: RV-IVRT obtained by the two methods was compared in 20
      consecutive patients as was the time from the R wave on the ECG to the onset of
      tricuspid flow (R-T), to the closure of the pulmonic valve (R-P), to the onset of
      early diastolic motion of the tricuspid annulus tissue (R-E) and to the end of
      the systolic motion (R-S). RESULTS: RV-IVRT obtained by the PW method was
      significantly (p < 0.001) shorter than RV-IVRT obtained by PW-DTI. R-S had
      significantly (p < 0.001) shorter duration than R-P, while there was no
      significant difference between R-E and R-T. CONCLUSIONS: The methods are not
      measuring the same interval. Only the PW method measures RV-IVRT according to the
      usual definition. Different reference values have to be used if the methods are
      used in the assessment of RV diastolic function.

PMID- 15513308
TI  - In northern Sweden myocardial infarction morbidity and case fatality are lowest
      in rural areas.
AB  - OBJECTIVES: Previous studies have shown differences in the main cardiovascular
      risk factors between communities of different sizes in northern Sweden, with
      serum cholesterol levels, systolic blood pressure and body mass index being
      higher, but with fewer smokers in the smallest communities. We wanted to see if
      there also were differences in the morbidity and 28-day case fatality in acute
      myocardial infarction (AMI) between communities of different sizes in this area.
      DESIGN: The Northern Sweden MONICA Project database of AMI was examined for the
      years 1985-1999 for age-adjusted morbidity and 28-day case fatality for each sex
      in relation to the size of the community where each case lived. RESULTS: The age
      standardized morbidity and 28-day case fatality were the lowest in the smallest
      communities where the risk factor burden previously was shown to be highest, and
      the highest in intermediate size communities. CONCLUSIONS: Other factors than
      conventional biomedical risk factors seem to either confer protection in the
      smallest communities or increase the AMI risk in larger communities.

PMID- 15513309
TI  - Evaluation of ST-segment changes during and after maximal exercise tests in one-,
      two- and three-vessel coronary artery disease.
AB  - OBJECTIVE: To relate ECG and heart rate (HR) variables during and after exercise
      testing with the presence of one-, two- or three-vessel disease defined by
      angiography. DESIGN: Seventy-three male patients with stable angina pectoris and
      angiographically verified coronary artery disease underwent a maximal exercise
      test. From 12-lead ECG recordings and computer averaging ST-amplitude and HR data
      were measured in consecutive 10-s intervals. RESULTS: In univariate analysis,
      patients with three-vessel disease had lower maximal exercise capacity, a shorter
      time to >1 mm ST-depression, more often a clockwise ST/HR recovery loop, more
      frequently a post-exercise downward ST-segment slope, and a greater ST-deficit at
      3.5 min after exercise than patients with one-vessel disease. In multivariate
      analysis, time to >1 mm ST-depression discriminated between patients with three-
      and one-vessel disease. In patients with an intermediate time to >1 mm ST
      depression a clockwise ST/HR recovery loop and/or a downsloping ST-segment in the
      post-exercise period were significantly more prevalent in severe vessel disease.
      CONCLUSION: Patients with three-vessel disease had a significantly shorter time
      to >1 mm ST-depression during exercise and more often an abnormal post-exercise
      ST/HR reaction than those with one-vessel disease.

PMID- 15513315
TI  - The benefits of continuous ultrafiltration in pediatric cardiac surgery.
AB  - BACKGROUND: Systemic inflammatory response and capillary leak syndrome, caused by
      extracorporeal circulation, have negative effects on the function of vital organs
      during the postoperative period. Modified ultrafiltration (MUF) has been
      developed as an alternative method to reduce the detrimental effects of
      cardiopulmonary bypass. The aim of this prospective, randomized study is to
      analyze the effects of MUF in a pediatric population undergoing congenital
      cardiac surgery. METHODS: Twenty-seven patients who underwent open-heart surgery
      at our institution were included in this prospective study. They were randomized
      into two groups as follows: Group I (n=14) of conventional ultrafiltration during
      bypass and Group II (n=13) receiving both conventional and modified
      ultrafiltration during and after the cessation of the bypass, respectively. The
      amount of prime volume, postoperative chest drain loss, transfusion requirements,
      hemodynamical parameters, duration of mechanical ventilatory support, and length
      of intensive care unit stay were compared between the two groups. During the
      postoperative period, the concentrations of hematological, biochemical and
      inflammatory parameters were also compared by analyzing the blood samples
      obtained at various time points. RESULTS: MUF resulted in a significant increase
      in hemoglobin, hematocrit and platelet levels, and significantly reduced the
      amount of chest tube output and transfused blood and blood products. MUF also
      shortened the duration of postoperative mechanical ventilatory support, length of
      the intensive care unit stay and improved postoperative hemodynamical parameters.
      During the early postoperative hours, IL-8 is significantly reduced in patients
      undergoing MUF, however, the concentrations of IL-8 were similar in both groups
      at the end of 24 h. CONCLUSIONS: MUF decreases the duration of mechanical
      ventilatory support, the length of intensive care unit stay, the need for blood
      transfusion and improves postoperative hemodynamics. It is associated with
      increased levels of hemoglobin, hematocrit and platelets. We can conclude that
      MUF attenuates the inflammatory response by decreasing the levels of inflammatory
      mediators.

PMID- 15513311
TI  - Cause of death during 13 years after coronary artery bypass grafting with
      emphasis on cardiac death.
AB  - OBJECTIVE: To describe the cause of death in the long term after coronary artery
      bypass grafting (CABG) with particular emphasis on cardiac death. PATIENTS AND
      SETTING: All the patients in western Sweden without simultaneous valve surgery
      and without previous CABG who underwent CABG in 1988-1991 in Goteborg, Sweden.
      DESIGN: Prospective, observational study for 10.6-13.6 years (i.e. until the end
      of 2001). Various factors contributing to death were described, with the emphasis
      on cardiac death. RESULTS: In all, 2000 patients were included in the survey. The
      all-cause mortality rate was 39%. Fifty-eight per cent of all deaths were judged
      as cardiac deaths. The most frequent cause of death was heart failure (65% among
      patients who died within 30 days after CABG and 36% among those who died >30 days
      after CABG). The second most common cause of death was myocardial infarction (56
      and 29%, respectively), followed by cancer (0 and 24%, respectively), stroke (21
      and 18%, respectively) and infection (8 and 11%, respectively). CONCLUSION: The
      factors most commonly contributing to death in the long term after CABG were, in
      order of frequency, heart failure, myocardial infarction, cancer, stroke and
      infection.

PMID- 15513319
TI  - How good are clinical chemistry laboratories at analysing ethylene glycol?
AB  - The results of an external proficiency test of clinical chemistry laboratories in
      Sweden when the target analyte was ethylene glycol (EG) are presented. Specimens
      of plasma were spiked with EG (10% w/v) to give assigned concentrations ranging
      from 5 to 50 mmol/L. Over a period of 6 years, two control specimens of plasma
      were sent for analysis on 21 occasions to between 14 and 20 participating
      laboratories as a declared proficiency trial. The analytical precision between
      and within laboratories was determined by spiking the plasma specimens with the
      same concentration of EG so that the results reported back could be considered a
      duplicate determination. On one occasion propylene glycol (PG) was substituted
      for EG without informing the participants. The standard deviation (SD) within
      laboratories expressed as the coefficient of variation (CV) was 4.5% compared
      with 11.4% between laboratories. Results reported by laboratories using gas
      chromatography (GC) were in good agreement with those when an enzymatic method
      was used. The between-laboratory SD increased with concentration of EG in the
      specimen and at a mean concentration of 18 mmol/L, the pooled SD was 4.11 mmol/L
      (CV = 23%). Four laboratories reported finding EG in plasma when PG was the diol
      present; three laboratories used an enzymatic method and one used GC. Clinical
      laboratories that provide a toxicology service should regularly participate in
      external quality assurance schemes that include low-molecular-weight alcohols
      such as EG. Efforts should be made to standardize the analytical methods used for
      toxicological analysis.

PMID- 15513322
TI  - Thiol metabolism in preterm infants during the first week of life.
AB  - BACKGROUND: Oxidative stress is implicated in the pathogenesis of several
      complications of prematurity. The glutathione cycle is one of the most important
      intracellular antioxidant systems. The synthesis of glutathione may not be
      adequate in preterm neonates because of the low levels of cysteine available. The
      aim of this study was to evaluate cysteine and glutathione metabolism during the
      first week of life in preterm infants. METHODS: Plasma and erythrocyte thiol
      concentrations were measured in 78 preterm infants with a birthweight of 500-1500
      g, and erythrocyte glutamate-cysteine ligase (GCL), glutathione peroxidase (GPx),
      glutathione reductase (GR), glutathione S-transferases (GST) and glucose 6
      phosphatedehydrogenase (G6PDH) in 26 infants with a birthweight of 1000-1500 g.
      RESULTS: The mean (SD) plasma glutathione concentration increased from day 0 to
      day 1 (14.9 (7.1) vs. 27.7 (11.9) micromol/L, p < 0.001), and then decreased. The
      plasma cysteine concentration changed in the opposite direction (172 (59) vs. 129
      (42) micromol/L, p < 0.01). In infants with respiratory distress syndrome (RDS)
      the mean plasma glutathione concentration, but not cysteine, was lower on day 0
      compared with infants without RDS (11.7 (5.2) vs. 21.4 (5.6) micromol/L, p <
      0.01). Erythrocyte glutathione concentration decreased during the first week of
      life, whereas erythrocyte cysteine concentration increased significantly from day
      3 to day 7 (p < 0.01). Erythrocyte cysteine and glutathione concentrations had a
      positive correlation. The GCL and GR activities did not change, but GST and G6PDH
      activities decreased during the first week (p < 0.01). GPx activity decreased
      until day 3 (p < 0.01) and was higher on day 0 and day 1 in infants with RDS.
      CONCLUSIONS: Very low birthweight infants have an initial increase in plasma
      glutathione and initial decrease in plasma cysteine level during the first week
      of life, and also a positive correlation between erythrocyte cysteine and
      glutathione levels.

PMID- 15513314
TI  - Disastrous physiological effects of saline on the cell membrane demonstrated in
      cardiac cells.
AB  - OBJECTIVE: Saline is not an ideal storage solution. It has a low pH, no buffering
      capacity, and lacks other ions and nutrients. The objective was to explore the
      effects of storing cardiac muscle in saline. DESIGN: Guinea pig papillary muscles
      and ventricular myocytes were exposed to saline. The effects on action potential,
      membrane current, contraction and cell shortening were recorded in vitro at 35-37
      degrees C. RESULTS: Saline caused transient hyperpolarization of the resting
      potential (-140 mV), prolonged duration of the action potential, and increased
      contraction amplitude, which was later reversed. The membrane resting potential
      depolarized after a few minutes to about -15 mV and the preparations became
      unexcitable. The depolarized preparations remained slightly contracted. Upon
      reperfusion both papillary muscles and cells became unstable and spontaneously
      active. Storing myocytes in saline for only 2 h resulted in excessive cell death.
      CONCLUSION: Saline is disastrous for the function of the heart muscle and leads
      to depolarization, sustained contraction and unexcitable tissue. Saline should
      not be used as a storage medium, even for short periods of time.

PMID- 15513313
TI  - Cardioprotection afforded by ischemic preconditioning interferes with chronic
      beta-blocker treatment.
AB  - OBJECTIVES: The efficacy of ischemic preconditioning of the heart has remained
      controversial. We investigated whether chronic treatment with beta-blockers
      affects the ischemic preconditioning in the isolated rat heart model. DESIGN:
      Wistar rats were treated with propranolol (50 mg/kg/day, p.o.) (PRL), with
      nipradilol (10 mg/kg/day, p.o.) (NPL), or with vehicle, for 4 weeks. Isolated rat
      hearts were divided into global ischemia hearts (GI, PRL and NPL, each n=6) and
      ischemic preconditioned hearts (IP, PRL+IP and NPL+IP, each n=6). RESULTS:
      Significant differences in left ventricular pressure were observed between the
      PRL and PRL+IP, and between the NPL and NPL+IP groups. In the NPL group,
      significant amelioration and preservation of left ventricular peak pressure,
      coronary flow, reduction of infarct size, and NOx preservation were observed.
      Lipid peroxidation in the NPL group was significantly reduced before and after
      global ischemia compared to the GI group. CONCLUSIONS: The effect of ischemic
      preconditioning was abolished in the hearts of rats following oral treatment of
      propranolol or nipradilol. However, the administration of nipradilol protected
      the ischemic and reperfused myocardium, partly due to the prevention of lipid
      peroxide formation.

PMID- 15513312
TI  - Isoflurane produces only minor preconditioning in coronary artery bypass
      grafting.
AB  - OBJECTIVE: To investigate whether administration of isoflurane prior to
      cardiopulmonary bypass (CPB) could partly account for the observed protection of
      the myocardial function and to decrease myocardial injury in patients undergoing
      coronary artery bypass grafting (CABG). METHODS: Thirty-four patients with stable
      angina who were scheduled for isolated elective CABG operations were randomized
      into the control group or isoflurane (ISO) group. In the ISO group, isoflurane
      was inhaled for 5 min followed by another 5-min washout period before commencing
      CPB. The control group did not receive isoflurane. Hemodynamic data and
      biochemical markers of myocardial injury were measured perioperatively. RESULTS:
      There were no adverse effects related to isoflurane. Cardiac index (CI) increased
      postoperatively as compared with the baseline. In the ISO group, there was a
      tendency for a greater increase of CI than that in the control group (p = 0.054,
      ANOVA for repeated measurements). At 1 h after CPB, the change of CI was much
      higher in the ISO group than that in the controls (p = 0.001). Both the creatine
      kinase cardiac isoenzyme (CK-MB) and troponin I (TnI) reached peak value at 6 h
      after CPB. Isoflurane patients released slightly less CK-MB than the controls
      postoperatively, but the difference was not significant (p = 0.16, ANOVA for
      repeated measurements). The release of TnI was similar in both groups (p = 0.65,
      ANOVA for repeated measurements). CONCLUSIONS: Administration of isoflurane prior
      to commencing CPB may bring an improvement in early hemodynamic performance after
      CABG operations.

PMID- 15513316
TI  - Tumor necrosis factor gene polymorphisms and inflammatory response in coronary
      artery bypass grafting patients.
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha), a key factor in the
      inflammatory cascade, has been implicated in coronary artery disease. Two
      biallelic polymorphisms in the TNF gene locus (TNFA at position -308 and TNFB at
      +252) may influence TNF-alpha production. Individuals with the rare TNFA2 allele
      or TNFB2 homozygosity have augmented TNF-alpha production. We investigated the
      genotypes associated with increased TNF-alpha production in coronary artery
      bypass grafting (CABG) patients and if these genotypes influence the magnitude of
      the postoperative inflammatory response. METHODS: TNF gene polymorphisms were
      analyzed by multiplex fluorescent solid-phase minisequencing in 86 CABG patients.
      Plasma concentrations of TNF-alpha, IL-6 and C3a and C-reactive protein (CRP)
      were analyzed before and after surgery in 45 of the patients and compared with
      genetically high and low TNF-alpha producers. RESULTS: Thirty percent of the
      patients carried the TNFA2 allele and 45% were TNFB2 homozygous. The allelic
      frequencies were TNFA1/TNFA2 = 0.84/0.16 and TNFB1/TNFB2 = 0.32/0.68. Pre- and
      postoperative levels of TNF-alpha, IL-6, C3a and CRP did not differ significantly
      between genetically high and low TNF-alpha producers. CONCLUSIONS: The frequency
      of high TNF-alpha producing genotypes in a CABG population was comparable to that
      previously reported from normal populations. Furthermore, we found no evidence
      that the investigated TNF-alpha gene polymorphisms influence postoperative
      inflammatory response after uncomplicated coronary surgery.

PMID- 15513318
TI  - Neuroendocrine testing in community patients with heart disease: plasma N
      terminal proatrial natriuretic peptide predicts morbidity and mortality stronger
      than catecholamines and heart rate variability.
AB  - BACKGROUND: Patients with heart disease are at risk of developing congestive
      heart failure (CHF). Neurohormonal activation may make an important contribution.
      AIM: In stable heart patients from primary care, to examine neuroendocrine
      markers of cardiac performance for the association to cardiac dysfunction,
      morbidity and mortality. METHODS: Plasma N-terminal atrial natriuretic peptide (N
      ANP), catecholamines, 24-h ECG and blood pressure, serum urea and creatinine,
      echocardiography, chest X-ray and physical examination were performed. Death was
      recorded during 5 to 7 years of follow-up. RESULTS: The study included 56
      patients. Mean age was 71 years, 54% were men, 43% had clinical signs of CHF, 39
      + 52 + 9% were in NYHA I + II + III, 34% had echocardiographic cardiac
      dysfunction, and 18 died during follow-up. N-ANP was related to all subtypes of
      cardiac dysfunction (p < 0.05). Catecholamines and premature ventricular captures
      (PVC) were related to valvular and systolic dysfunction, but heart rate
      variability and dipping blood pressure were not (p > 0.05). On multivariate
      analyses only, N-ANP and PVC were associated with clinical signs of CHF,
      echocardiographic cardiac dysfunction, and mortality (p < 0.05). CONCLUSIONS:
      Plasma N-ANP was stronger than catecholamines and variables of 24-h monitoring
      (blood pressure and electrocardiogram) in predicting morbidity and mortality,
      thereby supporting the use of cardiac natriuretic peptides (i.e. N-ANP, BNP, or N
      BNP) as the most valuable biomarker in community patients at risk of CHF.

PMID- 15513324
TI  - Serum cardiac troponin T in patients hospitalized with heart failure is
      associated with left ventricular hypertrophy and systolic dysfunction.
AB  - BACKGROUND: Cardiac troponin T (cTnT) is a highly sensitive and specific marker
      of acute myocardial infarction. Serum cTnT is also slightly elevated in patients
      with severe heart failure and is associated with left ventricular hypertrophy
      (LVH) in patients treated with haemodialysis. In this study serum cTnT
      concentrations and echocardiographic findings were investigated in heart failure
      patients without acute coronary syndrome. cTnT was also compared with other
      cardiac markers and plasma levels of brain natriuretic peptide (BNP). METHODS:
      Twenty-six patients hospitalized with heart failure were included in the study.
      Echocardiographic measurements and blood sampling were carried out 12-36 h after
      admission. Serum cTnT (3rd generation assay), cardiac troponin I (cTnI), creatine
      kinase MB (CKMB) and CK were measured. Plasma BNP was analysed using the
      Shionoria assay. LVH was defined as left ventricular mass index (LVMI) > 125 g/m
      for males and > 110 g/m for females. Left ventricular systolic function was
      estimated from the mitral annulus motion (AV-mean LV). RESULTS: Median cTnT was
      0.012 (< 0.010-0.032) microg/L. Sixty-two percent of the patients (16 of 26) had
      elevated serum cTnT >or= 0.010 micro/L. cTnT was positively correlated with CKMB
      (rho = 0.40, p = 0.04) and BNP (rho = 0.43, p = 0.03), but not with cTnI and CK.
      A negative correlation was found between cTnT and AV-mean LV (rho = -0.58, p =
      0.007), and there was a positive correlation between cTnT and LVMI (rho = 0.44, p
      = 0.03). No other analyte was correlated to LVMI. CONCLUSIONS: Serum cTnT but not
      cTnI was associated with left ventricular dysfunction and LVH in patients
      hospitalized with heart failure. This explains why cTnT tends to be slightly
      elevated in patients with heart failure without symptoms of acute myocardial
      ischaemia.

PMID- 15513320
TI  - Elevated plasma beta-endorphin/beta-lipotropin concentration following a radius
      fracture.
AB  - Plasma beta-endorphin/beta-lipotropin concentration was assessed soon after a
      fracture. Blood samples from 14 patients with radius fractures were obtained from
      both arms soon after admission to the hospital (mean 245 min) after the accident.
      Follow-up samples were taken after healing of the fractures. Higher plasma beta
      endorphin/beta-lipotropin concentrations were found in blood samples taken soon
      after a fracture in both arms compared with the concentrations after healing of
      the fracture. At admission, mean beta-endorphin/beta-lipotropin concentrations in
      the fractured and the contralateral arms were 12.7 pmol/L and 13.2 pmol/L, and
      after recovery 11.1 pmol/L and 11.5 pmol/L (p = 0.012 and p = 0.041),
      respectively. The pain decreased according to the visual analogue scale (VAS) (0
      10) from 4.64 at admission to 0.58 after healing (p < 0.001). In conclusion, this
      study showed that beta-endorphin/beta-lipotropin concentrations are increased in
      both arms following a radius fracture compared to the level after the fracture
      has healed.

PMID- 15513321
TI  - Characterization of blood vessels in bone marrow from patients with chronic
      myeloid leukemia and polycythemia vera.
AB  - Angiogenesis is a feature of hematological malignancies which may provide
      prognostic information. However, there is, as yet, no established marker for
      leukemia-associated vessels in bone marrow. In this study, immunohistochemical
      stainings for von Willebrand factor (vWf), CD34, Tie-2, angiomodulin, glycodelin,
      cycloxygenase-2 (Cox-2) and endoglin were compared in order to identify the bone
      marrow vasculature. Chronic myeloid leukemia (CML), a disease displaying intense
      angiogenesis, and polycythemia vera (PV), a disease with a low microvascular
      density (MVD), were studied, as well as normal bone marrow. Only vWf, CD34 and
      Tie-2 stained the bone marrow endothelium. Although more vessels were stained for
      vWf than for CD34, there was no evidence that vWf stained more disease-associated
      vessels. In double staining, Tie-2 co-localized with CD34, but vessels staining
      only for Tie-2 were also found. However, the number of Tie-2-positive vessels did
      not correlate to either the MVD or the disease. Angiomodulin, glycodelin, Cox-2
      and endoglin did not stain vessel-like structures. In conclusion, estimating the
      MVD by means of CD34 staining appears to be the most reliable method, but none of
      the tested molecules qualified as a specific marker for leukemia-associated
      vessels in the bone marrow.

PMID- 15513323
TI  - Circulating concentrations of hemostatic factors and two "steroid sensitive
      proteins" during oral hormone replacement therapy in women with coronary heart
      disease.
AB  - OBJECTIVE: To study a possible use of sex hormone-binding globulin (SHBG) and
      corticosteroid-binding globulin (CBG) as markers for changes in hemostatic
      factors during oral postmenopausal hormone replacement therapy (HRT). METHODS:
      Twenty-eight postmenopausal women were treated with oral conjugated equine
      estrogens+oral medroxyprogesterone acetate (CEE + MPA, n = 15) or with placebo (n
      = 13). Serum SHBG, CBG, testosterone, cortisol and plasma coagulation factors,
      coagulation inhibitors and markers of coagulation activation were measured before
      and after 6 and 12 months of treatment. RESULTS: Pretreatment plasminogen
      activator inhibitor 1 (PAI-1) levels correlated negatively to SHBG and
      antithrombin III (AT III) negatively to total and free cortisol. In the CEE + MPA
      group, CBG, SHBG and Factor VII increased, and PAI-1, AT III and free
      testosterone decreased during treatment. No significant changes were found in
      plasma von Willebrand factor antigen, thrombin-antithrombin complex, fibrin D
      dimer and fibrinogen. A significant, negative correlation was found between
      changes in SHBG and PAI-1. No changes were found in the placebo group.
      CONCLUSION: The only correlation found between changes in "steroid sensitive"
      proteins and hemostatic factors was between increased SHBG and a possibly
      beneficial effect of estrogens, i.e. decreased PAI-1 values. SHBG or CBG could
      not be used as predictors of increased cardiovascular risk during postmenopausal
      oral HRT.

PMID- 15513326
TI  - Reliability of PSA circulating cells as markers of metastatic prostate cancer.

PMID- 15513325
TI  - Highly sensitive determination of C-reactive protein on the Innotrac Aio!
      immunoanalyzer.
AB  - C-reactive protein (CRP) is a widely recognized indicator of inflammation.
      Prospective studies have shown that CRP can be used to predict the risk of future
      cardiovascular events in apparently healthy subjects. Clinical and laboratory
      studies have also shown that inflammation has an important role in the
      inititation, progression and destabilization of atheromas, which makes high
      sensitivity CRP determinations valuable in cardiovascular risk assessment.
      Innotrac Aio! is a fully automated random-access immunoanalyzer using a unique
      all-in-one (Aio!) dry reagent concept and time-resolved fluorometric detection.
      In this study, the analytic performance of the Innotrac Aio! ultrasensitive CRP
      assay (usCRP) was evaluated. The analytical detection limit was 0.003 mg/L, the
      limit of quantification was <or= 0.03 mg/L and the carry-over result was within
      acceptable limits. Within-assay CVs obtained in lithium-heparin plasma at five
      concentrations ranged within 3.2 and 24.9%. Inter-assay precision using lithium
      heparin plasma pools and commercial controls was 6.2-8.6% at concentrations of
      0.17-33.3 mg/L. The inter-assay precision at a concentration of 0.04 mg/L using
      the serum pool was 67%. Regression analysis between Aio! usCRP and Cobas Integra
      CRP latex (Roche Diagnostics) using lithium-heparin plasma samples yielded the
      following results: correlation coefficient 0.983, slope 1.17 (< 50 mg/L) and
      correlation coefficient 0.974, slope 1.137 (< 10 mg/L). The correlation
      coefficient between Integra and Aio! usCRP assays using serum samples was 0.979
      and the slope 1.106. Regresssion analysis between Aio! usCRP and Hitachi CRP
      (Latex) HS using serum samples revealed the following results: correlation
      coefficient 0.942, slope 0.879 (< 20 mg/L) and correlation coefficient 0.973,
      slope 0.983 (< 10 mg/L). EDTA whole blood samples correlated well with the
      corresponding plasma samples. Innotrac Aio! usCRP assay was found to be linear in
      the CRP concentration range of 0.09-62 mg/L. In the first quartile (0-25th
      percentile), 2nd quartile (25th-50th percentile), 3rd quartile (50th-75th
      percentile) and 4th quartile (75th-100th percentile), the mean CRP values were
      0.16 mg/L, 0.52 mg/L, 1.24 mg/L and 4.39 mg/L, respectively.

PMID- 15513327
TI  - Management issues in dyspepsia: current consensus and controversies.

PMID- 15513328
TI  - Hypergastrinaemia induced by partial corpectomy results in development of
      enterochromaffin-like cell carcinoma in male Japanese cotton rats.
AB  - BACKGROUND: Among inbred female cotton rats (Sigmodon hispidus) 25%-50% of the
      animals develop spontaneous gastric carcinomas, whereas males have an incidence
      of less than 1%. The carcinomas are enterochromaffin-like (ECL)-cell derived.
      Animals with gastric carcinomas also have hypergastrinaemia and gastric
      hypoacidity, but the mechanism behind the hypoacidity is unknown. Carcinomas have
      been found in all female cotton rats with spontaneous hypergastrinaemia lasting
      more than 4 months, and a gastrin receptor antagonist prevents the development of
      carcinoma. The purpose of the present study was to investigate whether induced
      hypergastrinaemia in male cotton rats would also result in carcinomas. METHODS:
      Hypergastrinaemia was induced by partial corpectomy of male cotton rats, aiming
      at removal of 80%-90% of the corpus. A control group was sham-operated. RESULTS:
      All partially corpectomized animals developed persistent hypergastrinaemia. Six
      months after the operation, 9 out of 13 partially corpectomized animals developed
      gastric cancer. In the dysplastic mucosa surrounding the tumours there was an
      increase in chromogranin A immunoreactive cells, where numerous cells also were
      stained using the Sevier-Munger technique. Tumour tissue also contained cells
      that were chromogranin A positive and stained by Sevier-Munger. CONCLUSIONS: ECL
      cell carcinomas can be induced in male cotton rats by partial corpectomy. This
      supports a previous statement that spontaneous carcinomas in female cotton rats
      are caused by gastric hypoacidity and hypergastrinaemia. In hypergastrinaemic
      animals, ECL-cell carcinomas develop independently of gender within a relatively
      short period of time, and cotton rats therefore represent an interesting model
      for studying gastric carcinogenesis.

PMID- 15513330
TI  - Drink tests in functional dyspepsia: which drink is best?
AB  - BACKGROUND: Drinking capacity is often reduced in functional dyspepsia. Drink
      tests may therefore have diagnostic potential. A simple drink test in combination
      with ultrasonography was applied in this study, the aim being to find the best
      drink for this test. METHODS: On separate days, 10 patients with functional
      dyspepsia (FD) and 10 healthy controls (C) drank three different test meals
      (Nutridrink 150 kcal/100 mL, meat soup 4 kcal/100 mL and water) at a rate of 100
      mL/min until maximal drinking capacity. Intragastric volume at maximal drinking
      capacity was determined using 3-dimensional ultrasonography. RESULTS: Drinking
      capacity (P < 0.05) and intragastric volume (P < 0.01) were significantly lower
      in patients than in the controls with the meat soup meal, but not with Nutridrink
      or water. Gastric emptying distinguished significantly (P < 0.05) between
      patients and controls only with Nutridrink. Gastric emptying of Nutridrink was
      significantly correlated to the rate by which nausea was induced (P = 0.02),
      while gastric emptying of meat soup was significantly negatively correlated to
      the rate by which fullness was induced (P < 0.05). Receiver operating
      characteristic (ROC) analysis indicated that optimal discrimination between
      patients and controls was obtained by the combined test results of symptoms per
      intragastric volume using meat soup as the test meal. CONCLUSION: For the non
      invasive diagnosis of functional dyspepsia by a rapid drink test in combination
      with ultrasonography, a meat soup meal is preferable compared to Nutridrink or
      water.

PMID- 15513333
TI  - Increasing prevalence of coeliac disease in Swedish children: influence of
      feeding recommendations, serological screening and small intestinal biopsy
      activity.
AB  - BACKGROUND: The prevalence of coeliac disease (CD) in Swedish children has
      attracted considerable interest over the past few decades, and especially the
      influence of feeding habits on the increased incidence. A national study has
      reported a trend towards a decrease in incidence after a change in infant feeding
      recommendations was introduced in 1996. The aim of this study was to evaluate, in
      a geographically defined area, the change in incidence with time and the
      influence of the introduction of antibody analysis. METHODS: Cases of suspected
      paediatric CD between 1980 and 2003 were studied for prevalence, biopsy findings
      and antibody analyses. RESULTS: A total of 2029 children were investigated by
      small intestinal biopsy, yielding 554 CD cases. The area initially showed the
      same trend as the national study, but the annual incidence rate is now increasing
      again. Median age at diagnosis has increased significantly since 1997 from less
      than 2 years of age to above 5 years. Cumulative incidence at 2 years of age is
      much higher for the birth cohorts 1983-96 than 1980-82 or 1997-2001. Diagnostic
      accuracy was significantly higher after the introduction of antigliadin (AGA)
      analysis, and especially after antiendomysium (EMA) analysis. CONCLUSIONS: The
      incidence rate of CD in small children in our region has varied widely over the
      24-year period observed. Feeding practice and methods of investigation have
      changed during this period. The annual incidence rate for the total child
      population in 2003 was almost equal to the peak value observed in 1994. There
      were no conclusive results on whether antibody analysis had an influence on
      diagnostic activity, but this seems to have increased diagnostic accuracy.

PMID- 15513329
TI  - Biological in vitro effects of fibrin glue: fibroblast proliferation, expression
      and binding of growth factors.
AB  - BACKGROUND: Fibrin glue is used in the endoscopic therapy of bleeding
      ulcerations. Accelerated closure of ulcers has been documented for this treatment
      in comparison with other injection techniques; the biological reason, however,
      remains unclear. METHODS: In an in vitro model the effects of fibrin glue on the
      expression and secretion of growth factors by gastric epithelial (AGS, KATO III)
      and mesenchymal cells (fibroblasts) as well as their proliferative response and
      their interaction were compared with those of other matrices. RESULTS: Native
      fibrin glue does not release vascular endothelial growth factor (VEGF) but is
      able to bind this growth factor in biologically relevant concentrations of 152.6
      pg/mL. The addition of fibrin glue to a collagen type I matrix led to an
      increased proliferation rate of gastric wall fibroblasts. The transcription of
      VEGF and platelet-derived growth factor (PDGF) mRNA was significantly increased
      in epithelial cells. Co-culture of fibroblasts grown on fibrin glue containing
      matrix and epithelial cells resulted in an increased secretion of VEGF by both
      cell lines. CONCLUSIONS: Fibrin glue leads to increased proliferation of
      fibroblasts and local accumulation of VEGF. These findings might at least partly
      explain the accelerated closure of bleeding ulcers treated by fibrin glue
      injection.

PMID- 15513334
TI  - Crohn disease of the small bowel proximal to the terminal ileum: detection by MR
      enteroclysis.
AB  - BACKGROUND: Although Crohn disease (CD) can affect the entire alimentary tract,
      the proportion of patients with small-bowel inflammation proximal to the terminal
      ileum is still unclear. Magnetic resonance imaging (MRI) combined with small
      bowel enteroclysis can detect inflammatory lesions of the small bowel. Hence, we
      applied MR-enteroclysis to assess the percentage of patients with small-bowel
      inflammation proximal to the terminal ileum among patients with CD and abdominal
      pain. METHODS: Twenty-five consecutive patients with low, active CD of the colon
      and/or terminal ileum and episodes of abdominal pain were examined by both MR
      enteroclysis and conventional enteroclysis. The findings of MR-enteroclysis were
      compared with endoscopic and histological results in the terminal ileum and
      conventional enteroclysis in the small bowel proximal to the terminal ileum.
      RESULTS: In 13 of the 25 patients, inflammation of the small bowel proximal to
      the terminal ileum was shown by MR-enteroclysis, whereas in only 4 of the 25
      patients, signs of inflammation of the small bowel proximal to the terminal ileum
      were shown by conventional enteroclysis, all of which were demonstrated by MR
      enteroclysis. MR-enteroclysis confirmed the findings in 22 of 25 patients in whom
      endoscopy and histology had shown inflammation (16 of 18) or no inflammation (6
      of 7) of the terminal ileum. CONCLUSION: In symptomatic patients with CD even of
      low activity, inflammation of the small bowel proximal to the terminal ileum is
      frequent.

PMID- 15513332
TI  - Effect of a gluten-free diet on plasma nitric oxide products in coeliac disease.
AB  - BACKGROUND: Inducible nitric oxide synthase is expressed in the small intestine
      of patients with coeliac disease. This produces increased plasma concentration of
      nitric oxide end products (NOx), most marked in those ingesting gluten. The time
      course of change in NOx with a gluten-free diet (GFD) and its correlation with
      histology and coeliac serology were studied. METHODS: Fasting plasma NOx was
      determined by the Greiss reaction in 20 coeliac patients at diagnosis and 2, 4
      and 6 months after commencing a GFD. Endomysial and gliadin antibodies were
      checked at the same time. Duodenal biopsies were taken at diagnosis and at 6
      months, and then graded according to the Marsh classification. RESULTS: Plasma
      NOx fell rapidly following the introduction of a GFD (mean before GFD 95.8 microM
      to 61.5 microM at 2 months), and further still by 6 months (mean = 37.0 microM).
      Reductions at 2 and 6 months were statistically significant compared with
      baseline (P < 0.01 and P < 0.005, respectively: Wilcoxon signed ranks test).
      Plasma NOx was correlated with histological grade initially (P = 0.03: Kruskal
      Wallis) but not after 6 months on a GFD (P = 0.24). Coeliac serology correlated
      poorly with histology. CONCLUSIONS: Plasma NOx falls rapidly following GFD in
      coeliac disease and is related to histological grade initially. However, values
      vary widely between individuals, which may limit its use as a clinical tool.

PMID- 15513331
TI  - Recurrent abdominal pain in children revisited: irritable bowel syndrome and
      psychosomatic aspects. A prospective study.
AB  - BACKGROUND: Since Apley, more than 40 years ago, concluded that less than 10% of
      cases with recurrent abdominal pain (RAP) are of organic origin, medical
      technology has improved, the knowledge has expanded and new methods of
      investigation have been developed. The lack of organic findings in many children
      with RAP has led to the conclusion that psychological factors are important.
      METHODS: Forty-four children with RAP underwent an investigation programme to
      find organic abnormalities that might explain the symptoms. Current criteria for
      irritable bowel syndrome (IBS) in children were used to find out what proportion
      fulfilled these criteria, irrespective of the organic findings on clinical
      investigation. A standardized questionnaire, the CBCL (Child Behaviour
      Checklist), was used to evaluate emotional and behavioural disturbances in
      children referred for RAP. RESULTS: Thirteen out of 26 (50%) children with no
      signs of organic disease fulfilled the IBS criteria as opposed to 7 out of 18
      (39%) children in the group with organic findings (P = 0.68). The total score for
      the CBCL was in the normal range for 32 out of 36 of the children. CONCLUSIONS:
      We found a high proportion of children fulfilling the IBS criteria in both
      groups, thus organic abnormalities have to be excluded before making the IBS
      diagnosis. The results of the CBCL forms did not show any difference between
      children with organic versus those with non-organic abnormalities, both groups
      within the normal range.

PMID- 15513336
TI  - Clinical significance of elevated serum chromogranin A levels.
AB  - BACKGROUND: Chromogranin A (CgA) has been shown to be a useful marker in the
      diagnosis of neuroendocrine (NE) tumours. The clinical significance of CgA has
      been studied mostly in patients with known NE tumours. The diagnosis was
      evaluated in 153 consecutive patients in whom CgA was measured in a given time
      interval. METHODS: CgA in serum was measured by radioimmunoassay.
      Immunohistochemistry with an antibody against CgA was performed in tumours from
      patients with adenocarcinoma and elevated CgA levels using a conventional method
      and the more sensitive tyramide signal amplification (TSA) technique. RESULTS:
      Elevated serum CgA levels were found in 44 patients; 19 had NE tumours and 6 had
      tumours classified as adenocarcinomas. With the TSA technique, a high proportion
      of CgA-positive cells were disclosed in five of the adenocarcinoma patients.
      Patients with atrophic gastritis (no. 2) and patients treated with inhibitors of
      gastric acid secretion (no. 6) also had elevated levels of CgA. A modest increase
      in CgA levels was observed in 2 patients with renal impairment, and in 9 patients
      without any obvious cause. CONCLUSION: The current study confirms that serum CgA
      is a sensitive marker for the detection of NE neoplasia. Elevated levels found in
      patients with adenocarcinoma may indicate NE differentiation in the tumour. CgA
      is a useful tool in the monitoring of enterochromaffin-like (ECL) hyperplasia
      secondary to treatment with acid secretion inhibitors or atrophic gastritis.

PMID- 15513342
TI  - Capsule endoscopy: role of bowel preparation in successful visualization.
AB  - BACKGROUND: Lesions of the small bowel that cannot be detected by other
      techniques can be indentified by capsule endoscopy. Good preparation before any
      endoscopic procedure is the most important factor for patient safety, quality of
      care and cost effectiveness. This should also apply to capsule endoscopy. The aim
      of this study was to evaluate the quality and efficacy of preparation with oral
      sodium phosphate for capsule endoscopy. METHODS: A retrospective cohort study
      design was used. The study sample consisted of 32 consecutive patients scheduled
      for capsule endoscopy in two periods; the first 10 patients were prepared with
      overnight fasting only, and the next 22 with oral sodium phosphate. An
      experienced endoscopist and gastroenterology nurse, who were blinded to the
      method used, graded the quality of preparation. RESULTS: Small-bowel cleansing
      was significantly better in patients given sodium phosphate. Five patients (50%)
      received a poor preparation rating in the first period compared with only 1
      (4.5%) of the 22 patients given oral sodium phosphate (P = 0.01). Intraluminal
      fluid was noted in 9 patients (90%) in the first group after a mean of 53 +/- 60
      min, and in 17 patients (77%) in the second group after a mean of 158 +/- 71 min
      (P < 0.001). The proportion of non-ideal preparation was significantly higher in
      group 1 than in group 2, significant visualization disturbances being more
      prevalent in the first period. CONCLUSIONS: Bowel preparation with sodium
      phosphate before capsule endoscopy offers better visualization than overnight
      fasting alone and induces fewer disturbances by intraluminal turbid fluid.

PMID- 15513335
TI  - Fatigue in patients with primary sclerosing cholangitis.
AB  - BACKGROUND: The occurrence of fatigue in primary sclerosing cholangitis (PSC),
      its impact on quality of life and the role of concomitant inflammatory bowel
      disease (IBD) and coexisting irritable bowel syndrome (IBS) is unexplored.
      METHODS: Ninety-three patients with PSC, associated with IBD in 80% of cases and
      77 patients with IBD alone, were enrolled in the study. The patients completed
      the following questionnaires: the Fatigue Impact Scale (FIS), the Psychological
      General Well-Being Index (PGWB), the Gastrointestinal Symptom Rating Scale
      (GSRS), the Beck Depression Inventory (BDI) and diagnostic criteria for IBS.
      Questionnaire data were related to liver tests and the latest liver biopsy in the
      PSC patients. Two sex- and age matched controls from the general population (GP)
      were assigned to each PSC patient and these controls completed the FIS and the
      BDI. RESULTS: Total fatigue score did not differ significantly between patients
      with PSC and IBD alone. Median total fatigue score among GP subjects was 39 (13
      72), which was higher than in PSC (19 (6-52) (P = 0.02)) and in IBD patients (19
      (5-35) (P < 0.0001)). PGWB and GSRS scores did not differ between patients with
      PSC and IBD alone. Depression and general health (PGWB) were independent
      predictors for total fatigue score in PSC. No correlation was observed between
      fatigue in PSC and the severity of the liver disease. CONCLUSIONS: Fatigue in
      patients with PSC is related to depression but not to the severity of the liver
      disease. Both the PSC and IBD patients had lower total fatigue scores than
      subjects from the general population. This argues against fatigue as a specific
      symptom of PSC and IBD patients.

PMID- 15513337
TI  - Effect of treatment with the Molecular Adsorbents Recirculating System on
      arterial amino acid levels and cerebral amino acid metabolism in patients with
      hepatic encephalopathy.
AB  - BACKGROUND: Liver failure is associated with low concentrations of branched-chain
      amino acids and high concentrations of most other amino acids. In this study the
      effect of treatment with the Molecular Adsorbents Recirculating System (MARS) on
      arterial amino acid levels and cerebral amino acid metabolism was examined in
      patients with severe hepatic encephalopathy. METHODS: The study included seven
      patients with hepatic encephalopathy from fulminant hepatic failure (FHF) and
      five patients with hepatic encephalopathy from acute-on-chronic liver failure
      (AoCLF). Cerebral blood flow and cerebral arteriovenous differences in amino
      acids were measured before and after 6 h of treatment with MARS. RESULTS: During
      MARS treatment, the total arterial amino acid concentration decreased by 20% from
      8.92 +/- 7.79 mmol/L to 7.16 +/- 5.64 mmol/L (P < 0.05). The concentration
      decreased in all amino acids with the exception of the branched-chain amino
      acids. Fischer's ratio of branched-chain to aromatic amino acids increased from
      0.73 +/- 0.47 to 0.91 +/- 0.54 (P < 0.05). A net cerebral efflux of amino acids
      in patients with FHF (8.94 +/- 8.34 micromol/100 g/min) as well as AoCLF (7.35 +/
      24.97 micromol/100 g/min) was not affected by the MARS treatment. MARS had no
      effect on the cerebral metabolic rate of any single amino acid in either group.
      CONCLUSIONS: MARS treatment tends to normalize the arterial amino acid
      concentrations in patients with hepatic encephalopathy. Even though the overall
      reduction in plasma amino acids and improvement in amino acid dysbalance may well
      be beneficial, it was not accompanied by any immediate improvement in cerebral
      amino acid metabolism in patients with FHF or AoCLF.

PMID- 15513339
TI  - Somatosensory changes in the referred pain area in patients with acute
      cholecystitis before and after treatment with laparoscopic or open
      cholecystectomy.
AB  - BACKGROUND: Visceral pain can lead to hypersensitivity in the referred pain area.
      In patients with chronic visceral pain this somatic hypersensitivity can persist
      for years. As 25%-40% of patients continue to have symptoms after
      cholecystectomy, whereof no explanation for pain can be offered in up to 30%, it
      could be hypothesized that altered sensory characteristics induced by acute
      cholecystitis could persist in some patients and thus be responsible for
      postcholecystectomy pain. The aim of this study was to investigate the
      somatosensory sensitivity in the referred pain area in patients with acute
      cholecystitis before and after cholecystectomy. METHODS: Patients with acute
      cholecystitis were studied before (n = 30) and after (n = 18) treatment.
      Sensitivity to pinprick, heat, cold, pressure and single and repeated electrical
      stimulation was studied in the referred pain area and in the control area on the
      contralateral side of the abdomen. RESULTS: Significant hypersensitivity in the
      referred pain area was detected in patients with acute cholecystitis. The somatic
      sensitivity was normalized after cholecystectomy. CONCLUSIONS: Acute
      cholecystitis leads to hypersensitivity in the referred pain area. Persistent
      hypersensitivity, as earlier reported after chronic visceral pain, was not seen
      aftiser cholecystectomy, indicating that this mechanism may not play a major role
      in patients with postcholecystectomy pain syndrome. The possible role in patients
      operated on for chronic gallstone pain has still to be investigated.

PMID- 15513340
TI  - Covered transjugular intrahepatic portosystemic stents maintain lower portal
      pressure and require fewer reinterventions than uncovered stents.
AB  - BACKGROUND: The purpose of this study was to evaluate the patency, functional and
      haemodynamic results of expanded-polytetrafluoroethylene (ePTFE)-covered
      transjugular intrahepatic portosystemic shunts in patients with liver cirrhosis.
      METHODS: Thirteen patients with an ePTFE-covered transjugular intrahepatic
      portosystemic shunt stent (TIPSS) were prospectively evaluated at 6 and 12 months
      and compared with matched controls with mesh-wire uncovered TIPSS. RESULTS: At 6
      months, ePTFE-TIPSS showed a significantly lower porto-caval pressure gradient
      (PCPG) (9 (3-21) mmHg, P = 0.006), a lower rate of dysfunction (8% versus 54%, P
      = 0.03) and required fewer reinterventions (2 versus 13, P = 0.02); similar
      results were obtained after 12 months. This resulted in a reduction in the median
      cost for angiographic surveillance in the covered TIPSS group at 6 and 12 months
      (36% and 56% compared to the uncovered TIPSS group, P = 0.002), but total
      procedure-related costs were higher with the ePTFE-TIPSS (6 months: 3730 (3245
      6759) versus 1850 (1466-5479) euro/patient; 12 months: 3945 (3460-6759) versus
      2295 (1728-5694) euro/patient) due to the higher initial cost of the ePTFE
      covered TIPSS. CONCLUSIONS: The insertion of ePTFE-covered TIPSS results in
      better maintenance of lowered portal pressure and fewer reinterventions in
      patients with liver cirrhosis. There is strong evidence that the use of ePTFE
      TIPSS does not require regular surveillance to maintain primary patency, which
      may then improve cost-effectiveness.

PMID- 15513338
TI  - Extensive homology between the major immunodominant mitochondrial antigen in
      primary biliary cirrhosis and Helicobacter pylori does not lead to immunological
      cross-reactivity.
AB  - BACKGROUND: Primary biliary cirrhosis (PBC) is an immune-mediated chronic
      cholestatic disease characterized by the presence of antibodies directed
      predominantly against the E2 subunit of the pyruvate dehydrogenase complex (PDC
      E2). What provokes tolerance breakdown in PBC remains to be established, though
      there is evidence to indicate that microbes may induce anti-mitochondrial
      antibodies (AMA) through a mechanism of molecular mimicry. METHODS: Having found
      that urease beta (UREB)(22-36) antigen of Helicobacter pylori (HELPY) shares
      extensive (87%) similarity with PDC-E2(212-226), the major mitochondrial
      autoepitope, it was hypothesized that this would also lead to cross-reactivity.
      The UREB/PDC-E2 mimics were thus constructed and tested by ELISA in 112 PBC
      patients and 114 controls. RESULTS: Reactivity to PDC-E2(212-226) was found in
      104 patients but to UREB(22-36) in only 2. In these two patients, the double
      reactivity was not cross-reactive. The lack of surface antibody accessibility to
      UREB(22-36), as demonstrated through three-dimensional model prediction analysis,
      may explain this unexpected finding. There was some speculation on whether HELPY
      UREB(22-36) might act as a cross-reactive CD4 T-cell epitope. All seven PBC
      patients, tested in a standard proliferation assay against PDC-E2(212-226), gave
      a positive response. All seven were unresponsive to HELPY UREB(22-36). The
      pattern of reactivity to HELPY antigens by immunoblot was similar between anti
      PDC-E2-positive and negative PBC cases, as well as between PBC patients and
      controls. CONCLUSION: Contrary to common belief, extensive sequence homology
      (molecular mimicry) between self and microbe does not necessarily result in cross
      reactivity. It is therefore likely that, when present, cross-reactivity between
      self and microbes is of biological importance.

PMID- 15513341
TI  - Contractile response of femoral arteries in pigs with acute liver failure.
AB  - BACKGROUND: Acute liver failure (ALF) is characterized haemodynamically by a
      progressive hyperdynamic circulation. The pathophysiological mechanism is
      unknown, but impaired contractility of vascular smooth muscle may play an
      important role. The aim of this study was to evaluate the vascular response to
      stimulation with norepinephrine and angiotensin II in endothelium-denuded femoral
      artery rings. METHODS: Norwegian Landrace pigs weighing 27.1 +/- 0.5 kg (mean +/-
      sx (standard error of the mean)) were used. ALF was induced by performing a
      portacaval shunt followed by ligation of the hepatic arteries (n = 6). Sham
      operated animals served as controls (n = 5). Cumulative isometric concentration
      contraction curves were obtained after in vitro stimulation of the femoral artery
      rings with either angiotensin II (10(-13) - 10(-5) mol/L) or norepinephrine (10(
      13) - 10(-3) mol/L). RESULTS: Pigs suffering from ALF developed a hyperdynamic
      circulation with an increased cardiac index (P = 0.017) and decreased systemic
      vascular resistance index (P = 0.015). Studies of the hind leg revealed a
      decreased vascular resistance index and increased blood flow compared to sham
      operated controls (P = 0.003 and P = 0.01, respectively). Angiotensin II caused a
      concentration-dependent contraction of the arterial segments, with no significant
      differences in vascular responses between the two groups. Maximum force generated
      did not differ (55 +/- 7 versus 56 +/- 7 mN, P = 0.95). Furthermore, there were
      no differences for norepinephrine in the cumulative concentration-response curves
      and the maximum contractile force was not significantly different (87 +/- 8
      versus 93 +/- 16 mN, P = 0.55). CONCLUSIONS: This study documents for the first
      time that there are no signs of endothelium-independent peripheral vascular
      hyporesponsiveness to angiotensin II and norepinephrine in pigs with ALF.

PMID- 15513344
TI  - A novel breath test for the non-invasive assessment of small intestinal mucosal
      injury following methotrexate administration in the rat.

PMID- 15513343
TI  - Which types of stent, uncovered or covered, should be used in gastric outlet
      obstructions?
AB  - BACKGROUND: Self-expandable metallic stents (SEMS) have been widely used in
      inoperable malignant gastric outlet obstructions, but stent obstructions caused
      by tumor ingrowth and migration are a major problem of SEMS. The aims of this
      study were to assess the rate of stent restenosis, to identify lesion
      characteristics related to early restenosis by tumor ingrowth, and, in
      particular, to find suitable patient groups for uncovered or covered stents at
      first implantation. METHODS: Forty-nine patients were reviewed: stomach cancer in
      34 patients, primary duodenal cancer in 3 patients, pancreatic cancer in 5
      patients, and common bile duct cancer in 7 patients. In principle, uncovered
      stents were initially placed at the time when obstruction symptoms occurred and
      the endoscope would not pass through. Stent obstruction due to tumor ingrowth
      within 4 weeks after the first stent implantation was regarded as early stent
      restenosis. RESULTS: Technical success was seen in 49/49 patients (100%).
      Migration did not occur. Stent obstructions caused by tumor overgrowth were found
      in 2/49 patients (4.1%) after 1 month. Stent obstructions caused by tumor
      ingrowth occurred in 14/49 patients (28.5%), and 7 of them (14.3%) were found to
      have early restenosis. The only statistically significant factor for early
      restenosis was stenosis site, and early restenosis was more frequent in the
      postoperative anastomosis site in the current study; a) 2/18 antropyloric
      obstructions (11.1%), b) 1/15 pyloric and duodenal bulb obstructions (6.7%), c)
      0/10 duodenal second portion obstructions (0%), and d) 4/6 postoperative
      anastomosis site obstructions (66.7) (P < 0.05, 95% CI 0.003-0.005). CONCLUSIONS:
      Uncovered stents are technically feasible and effective for most malignant
      gastric outlet obstructions. However, because of frequent early restenosis among
      patients with postoperative anastomosis site obstructions, the placement of
      covered or simultaneous dual stents to prevent early restenosis should be
      considered when stenting postoperative anastomosis site obstructions.

PMID- 15513352
TI  - Diverticulitis: a new high-risk group for colorectal cancer?

PMID- 15513347
TI  - Budd-Chiari and inferior caval vein syndromes due to membranous obstruction of
      the liver veins: successful treatment with angioplasty and transcaval
      transjugular intrahepatic porto-systemic shunt.
AB  - The case is presented of a 25-year-old Caucasian patient with Budd-Chiari
      syndrome due to membranous obstruction of the liver veins and inferior caval vein
      syndrome as a result of secondary hyperplasia of the caudate lobe of the liver,
      obstructing the caval vein. Diagnosis was established by intravascular pressure
      measurements, ultrasound examinations and caval and liver vein angiograms.
      Treatment consisting of stent placement in the outlet of a hepatic vein and
      subsequent transjugular intrahepatic porto-systemic shunt (TIPS) insertion via
      the caval vein was successful. After 34 months of follow-up the stents remain
      open and the patient is symptom free. This successful combination of stent
      placement and TIPS has not been described before. The case report is followed by
      a review of the literature on the use of angioplasty in short hepatic vein
      stenosis and TIPS in Budd-Chiari syndrome. It is concluded that angioplasty and
      TIPS are safe and efficient procedures to reduce liver engorgement and
      complications of portal hypertension in selected patients with Budd-Chiari
      syndrome.

PMID- 15513346
TI  - Recurrent omphalitis in adults.
AB  - Recurrent omphalitis is seen more frequently in children, but clinicians world
      wide are occasionally challenged by cases of recurrent omphalitis in adults.
      Apart from folliculitis and infections associated with pilonidal cysts and
      piercing of the umbilical area, the clinician should consider the possibility of
      infected remnants of the allantois or the omphalomesenteric (vitelline) duct in
      adult patients with recurrent omphalitis. Imaging tests such as ultrasound and
      computed tomography scan frequently help to identify the exact cause of recurrent
      omphalitis. The combined surgical and medical management usually leads to cure of
      the problem.

PMID- 15513350
TI  - Lactose malabsorption and IBS.

PMID- 15513349
TI  - Colorectal cancer screening.

PMID- 15513355
TI  - Reliability of the [13C]-acetate breath test in the measurement of gastric
      emptying of ethanol solutions: a methodological study.
AB  - BACKGROUND: The [13C]-acetate breath test is a clinically well-established test
      for measuring gastric emptying of liquids and correlates significantly with
      scintigraphy. However, no studies have been undertaken to examine the
      relationship between gastric emptying measured by the [13C]-acetate breath test
      and ultrasonography. Furthermore, it is not known how ethanol may affect gastric
      emptying as measured by the [13C]-acetate breath test. This is particularly
      important because of the additional steps of absorption, metabolism and
      exhalation of the tracer involved in the [13C]-acetate breath test compared to
      the simple measurement of gastric emptying by ultrasonography. The aim of the
      present study was to examine the relationship between the gastric half emptying
      times measured by the [13C]-acetate breath test and by ultrasonography and to
      determine the effect of ethanol on the comparability between both methods.
      METHODS: On separate days, 10 healthy, fasted randomly selected subjects received
      the following solutions by gastric tube: 500 mL water, 4% and 10% (v/v) ethanol,
      5.5% and 11.4 % (w/v) glucose. Gastric half emptying times of the test solutions
      were simultaneously determined using the [13C]-acetate breath test and
      ultrasonography of the fundus and the antrum. RESULTS: The gastric emptying rates
      determined by ultrasonography of the fundus correlated significantly with the
      results obtained using the [13C]-acetate breath test for all test solutions (r =
      0.64-0.92, P < 0.05 for all), whereas ultrasonography of the antrum correlated
      significantly with the breath test only when water (r = 0.94, P = 0.001) was
      used. The difference between the mean half-emptying times obtained using the
      [13C]-acetate breath test and ultrasonography of the fundus was 55 +/- 1.8 min.
      This difference was significantly longer when 4% and 10% (v/v) ethanol solutions
      were given (61.2 +/- 3.3 and 71.2 +/- 2.9 min) compared to water (P < 0.05).
      CONCLUSIONS: A good correlation was found between gastric emptying as measured by
      the [13C]-acetate breath test and ultrasonography of the fundus. Measurements
      that were obtained using the [13C]-acetate breath test demonstrate a longer
      gastric half emptying time compared with those obtained using ultrasonography.
      This difference is even more marked when ethanol solutions are used. Presumably,
      this is because ethanol affects the absorption and/or the hepatic metabolism of
      the tracer. The [13C]-acetate breath test is therefore not a reliable gastric
      emptying test for comparison of different solutions, especially when ethanol
      containing liquids are used.

PMID- 15513345
TI  - Normalization of faecal calprotectin: a predictor of mucosal healing in patients
      with inflammatory bowel disease.

PMID- 15513356
TI  - Peptide YY release after colectomy in slow transit constipation.
AB  - BACKGROUND: The gut hormone peptide YY is abundant in the colonic mucosa.
      Circulating PYY inhibits gastrointestinal motility and decreases food intake. The
      aim was to determine whether colectomy decreases PYY release in patients with
      slow transit constipation. METHODS: Plasma PYY concentrations were measured in 10
      patients with slow transit constipation before and 3-24 months after total
      abdominal colectomy with ileorectal anastomosis, and in 8 healthy controls. A
      liquid meal was infused intraduodenally to stimulate PYY release. RESULTS:
      Postprandial PYY significantly (P < 0.05) increased from a basal value of 15.6 +/
      1.8 pM to a peak of 71.2 +/- 11.6 pM after colectomy. Basal and postprandial
      plasma PYY concentrations were not significantly different from the results
      before surgery. Fasting, but not postprandial, plasma peptide YY after colectomy
      was significantly higher than that in healthy volunteers, 10.9 +/- 0.9 pM.
      CONCLUSION: Despite removal of a major source of PYY-secreting cells, colectomy
      with ileorectal anastomosis does not induce major impairment of PYY release in
      slow transit constipation.

PMID- 15513354
TI  - Reduced relapse rate in duodenal ulcer disease leads to normalization of
      psychological distress: twelve-year follow-up.
AB  - BACKGROUND: The aim of this study was to elucidate the relationship between
      duodenal ulcer (DU) disease and psychological symptoms. METHODS: Sixty-four
      Helicobacter pylori-positive patients with frequently relapsing DUs (patient
      group 1) were compared with 78 control subjects without dyspepsia, starting 2
      years before and ending 10 years after eradication of H. pylori. Seven non
      relapsing and untreated patients (patient group 2) were also followed-up.
      RESULTS: The relapse rate was reduced from 100% per year in the two years before
      anti-H. pylori treatment to 0.3% per year after treatment in patient group 1. The
      reinfection rate was 0.7% per year. Anxiety and neuroticism were high at
      inclusion, but had normalized at the 10-year follow-up in relapse-free patients.
      There was no increase of gastro-oesophageal reflux symptoms during the 10 years
      after H. pylori eradication. CONCLUSIONS: Normalization of anxiety and
      neuroticism following cure of DU disease supports the view that the increased
      anxiety and neuroticism are consequences, and not causes, of the disease.

PMID- 15513353
TI  - Gastric acid secretion of normal Japanese subjects in relation to Helicobacter
      pylori infection, aging, and gender.
AB  - BACKGROUND: In Japan, where the incidence of gastric cancer is high, Helicobacter
      pylori infection could affect gastric acid secretion differently from that in
      Western countries. The aim of this study was to investigate the relationship
      between H. pylori infection, acid secretion, aging, and gender in normal Japanese
      subjects. METHODS: The study comprised 193 Japanese subjects who had undergone
      routine endoscopy. Gastrin-stimulated acid output was performed during the
      routine endoscopic examination using the endoscopic method of gastric acid
      secretory testing (EGT: endoscopic gastrin test), which has been reported
      previously. H. pylori status was determined by histology, rapid urease test, and
      serology. RESULTS: Mean EGT values were 3.9 +/- 1.5 mEq/10 min in H. pylori
      negative men, 1.6 +/- 2.5 in H. pylori-positive men, 2.2 +/- 0.9 in H. pylori
      negative women, and 1.5 +/- 1.2 in H. pylori-positive women. Although acid
      secretion was lower in H. pylori-positive subjects compared with H. pylori
      negative subjects in both men and women, the decrease was more marked in men with
      H. pylori infection. Multiple linear regression analysis showed that aging is
      positively associated with gastric acid secretion in the H. pylori-negative
      subjects, whereas a negative association was found between them in the H. pylori
      positive subjects. CONCLUSIONS: In Japanese subjects, aging affects gastric acid
      secretion differently depending on the status of H. pylori infection. H. pylori
      infection showed a stronger inhibitory effect on the acid secretion in men than
      in women. This gender-related difference in the susceptibility of acid secretion
      to H. pylori infection may explain the higher rates of gastric cancer in men in
      Japan.

PMID- 15513358
TI  - Phosphatidylcholine and lysophosphatidylcholine in intestinal mucus of ulcerative
      colitis patients. A quantitative approach by nanoElectrospray-tandem mass
      spectrometry.
AB  - BACKGROUND: A defective mucus composition represents a key pathogenetic factor
      for intestinal injury. Phosphatidylcholine (PC) is an essential component
      contributing to formation of a hydrophobic mucus layer. For evaluation of PC in
      the pathogenesis of inflammatory bowel disease, the concentration and composition
      of PC in the rectal mucus of patients with ulcerative colitis was determined.
      Electrospray ionization (ESI) tandem mass spectrometry (MS/MS) allows
      quantification of PC species and enables analysis of crude extracts. METHODS:
      Lipid extracts of material obtained by light scrapings of the intestinal lumen
      were analysed quantitatively by nanoESI MS/MS with synthetic internal PC and
      lysophosphatidylcholine (LPC) standards. PC and LPC species from rectoscopically
      acquired mucus aliquots of patients with ulcerative colitis were compared to
      Crohn disease and control subjects. RESULTS: Patients with inactive ulcerative
      colitis showed significantly less PC and LPC (median 346 [IQR: 230-405] pmol
      total PC/mg dry weight) in rectal mucus compared to Crohn disease (median 126
      [IQR: 465-1941] pmol total PC/mg dry weight) and control subjects (median 1285
      [IQR: 850-1639] pmol total PC/mg dry weight) (P < 0.05). The molecular species of
      PC and LPC were not significantly different between the groups. The most abundant
      species were PC 16:0/18:1; PC 16:0/18:2; PC 18:0/18:1; PC 18:0/18:2; LPC 16:0;
      and LPC 18:0. CONCLUSION: NanoESI MS/MS is a suitable tool for analysing and
      quantifying small amounts of PC in human mucus. Patients with ulcerative colitis
      have significant less PC in their intestinal mucus despite a comparable PC
      molecular species composition pattern. This suggests that a low amount of
      protective mucus PC is a characteristic feature in ulcerative colitis and
      explains an increased susceptibility to luminal contents.

PMID- 15513357
TI  - Atopic manifestations are more common in patients with Crohn disease than in the
      general population.
AB  - BACKGROUND: The role of TNF-alpha in Crohn disease is now well established and
      anti-TNF-alpha is frequently used as a second- or third-line treatment. Tumor
      necrosis factor-alpha (TNF-alpha) is traditionally associated with macrophages
      but has recently also been found in mast cells of the ileal wall in patients with
      Crohn disease. As it is well known that mast cells and TNF-alpha play important
      roles in atopic manifestations like asthma, allergic rhinitis; and eczema the aim
      of this study was to investigate whether these are seen more commonly in Crohn
      patients than in the general population. METHODS: Patients with Crohn disease (n
      = 308), aged 18-50 years, living in the Linkoping region in southeast Sweden,
      were asked to answer a questionnaire regarding the presence of any kind of atopic
      manifestations. The questionnaire was also sent to 930 controls collected from
      the Southeastern Region Population Registry. The controls were matched according
      to age, sex, and place of residence. RESULTS: The response rate among the Crohn
      patients was 91% (280/308) and among controls 84% (779/930). Eczema was a
      significantly more frequent manifestation, being almost twice as common in Crohn
      patients (27%) as in the general population (16%). Adjustment by logistic
      regression for place of residence, gender, age and coexistence of any other
      atopic manifestation did not change the odds ratios significantly. CONCLUSION:
      Atopic manifestations as a group, and eczema as a single manifestation, are
      significantly more frequent in Crohn patients than in the general population.

PMID- 15513364
TI  - Abdominal pain and patient overall and cosmetic satisfaction one year after
      cholecystectomy: outcome of a randomized trial comparing laparoscopic and
      minilaparotomy cholecystectomy.
AB  - BACKGROUND: Previous studies with long-term follow-up after cholecystectomy have
      shown that residual abdominal symptoms are common. Laparoscopic cholecystectomy
      (LC) and minilaparotomy cholecystectomy (MC) can both give a smoother, early
      postoperative course than conventional open cholecystectomy (OC). The present
      study concerns abdominal pain and patient overall and cosmetic satisfaction one
      year after LC and MC. METHODS: In a prospective, single-blind study, 724 patients
      were randomly allocated to LC or MC. Patients completed questionnaires including
      items concerning abdominal pain before and one year after surgery and overall and
      cosmetic satisfaction one year after surgery. RESULTS: There was no difference in
      reduction of abdominal pain between LC and MC patients. For four different
      aspects of abdominal pain, 31%, 24%, 30% and 16% of patients operated with LC
      reported residual abdominal pain one year after surgery. The corresponding
      figures for MC were 28%, 20%, 27% and 18% (P values 0.55, 0.32, 0.55 and 0.63,
      respectively). According to questionnaire answers, there was no significant
      difference in the cosmetic result and overall patient satisfaction between LC and
      MC patients. CONCLUSIONS: There are no differences between laparoscopic and
      minilaparotomy cholecystectomy in long-term outcome regarding abdominal pain and
      patient overall and cosmetic satisfaction. A large proportion of patients have
      abdominal pain one year after cholecystectomy. Future studies should include
      preoperative assessment and indications for cholecystectomy.

PMID- 15513362
TI  - Ultrasound imaging of flow patterns in liver metastases from colorectal cancer.
AB  - BACKGROUND: The ability of colour Doppler, power Doppler and echo-enhanced
      Doppler imaging to detect the blood flow in liver metastases from colorectal
      cancer was investigated. An evaluation was then made to determine whether the
      flow pattern could be used as an indication of disease elsewhere. METHODS: Forty
      two patients with hepatic metastases from colorectal cancer were examined, 8 of
      whom had local recurrence of their colorectal cancer. Seventy-seven liver
      metastases were evaluated with colour Doppler and power Doppler, and the presence
      or absence of a Doppler signal in the halo or centre was noted. Forty-three of
      these metastases were further examined after contrast media echo-enhancement.
      RESULTS: Signals from the peripheral halo were detected by colour Doppler imaging
      in 34% of the metastases, and in 77% by power Doppler (P < 0.001). Use of
      contrast media enhanced the power Doppler detection rate to 98% (P < 0.005).
      Central signals were detected by power Doppler in 12 patients, 8 (66%) of whom
      also had local recurrence. Thirty patients had neither local recurrence nor
      central signals, as detected by power Doppler (P < 0.001). CONCLUSION: The
      results indicate that the halo in liver metastases corresponds to the vascular
      flow. There seems to be an association between metastases showing a central power
      Doppler flow and local tumour recurrence.

PMID- 15513360
TI  - Mutational activation of the RAS-RAF-MAPK and the Wnt pathway in small intestinal
      adenocarcinomas.
AB  - BACKGROUND: Adenocarcinomas of the small and the large intestine share risk
      factors and morphological features but both tumor types seem to follow different
      genetic pathways. The aim of this study on small intestinal carcinomas was to
      analyze alternative mechanisms of activation of pathways that are typically
      affected in colorectal cancer. METHODS: Twenty-one sporadic carcinomas were
      investigated for mutations in KRAS, BRAF, the beta-catenin gene CTNNB1, and the
      mutational cluster region of APC. Immunohistochemical analysis was performed with
      a monoclonal antibody for beta-catenin, the transcriptionally active downstream
      component of wnt signaling. RESULTS: Oncogene mutations were found in 13 (62%)
      small intestinal adenocarcinomas. Twelve tumors displayed a KRAS mutation, and a
      novel BRAF mutation at codon 603/604 was seen in one carcinoma without KRAS
      mutation. One tumor harbored a CTNNB1 mutation consisting of an insertion of 247
      nucleotides deriving from chromosome 9. APC mutations were identified in 2
      tumors. Immunohistochemistry demonstrated nuclear accumulation of beta-catenin in
      5 carcinomas. These carcinomas included the tumor with a CTNNB1 mutation but not
      those with APC mutations. CONCLUSIONS: Our data show frequent activation of the
      RAS-RAF-MAPK pathway through mutations of either KRAS or, infrequently, BRAF.
      Activation of the wnt pathway through accumulation of beta-catenin may have a
      role in a subset of small intestinal adenocarcinomas but in contrast to
      colorectal carcinoma, accumulation of beta-catenin is generally not caused by
      inactivating APC or activating CTNNB1 mutations.

PMID- 15513367
TI  - Stool protein analysis by two-dimensional gel electrophoresis and mass
      spectrometry.

PMID- 15513369
TI  - Successful laserlithotripsy in Bouveret's syndrome using a new frequency doubled
      doublepulse Nd:YAG laser (FREDDY).
AB  - Gastric outlet obstruction as a result of gallstone (Bouveret syndrome) is a rare
      but serious complication of cholelithiasis. In many cases, surgery has been
      conducted for treatment. In recent years, minimal invasive treatment modalities
      (e.g. shockwave lithotripsy) have been shown to be effective in some of those
      patients. Laserlithotripsy has so far been described in two cases with a
      Rhodamine-6G dye laser. We present the case of a 90-year-old woman with duodenal
      obstruction due to a huge gallstone. The patient was referred to our hospital
      because attempts at endoscopic extraction and extracorporeal shockwave
      lithotripsy had failed. The man was treated successfully in just one session with
      a new cost-efficient frequency doubled doublepulse Nd:YAG laser (FREDDY) using a
      total of 5726 laser pulses (120 mJ pulse energy, 10 Hz pulse repetition rate) and
      recovered rapidly. Laserlithotripsy can be considered an effective non-invasive
      therapeutic alternative to surgical treatment in Bouveret's syndrome, especially
      in old or high-risk patients.

PMID- 15513361
TI  - Circulating level of hepatocyte growth factor as a useful tumor marker in
      patients with early-stage gastric carcinoma.
AB  - BACKGROUND: Although conventional tumor markers including carcinoembryonic
      antigen (CEA) and carbohydrate antigen (CA19-9) have been used in gastric cancer
      patients, clinically useful markers of early gastric cancer have not been
      identified. The present study was designed to clarify the clinical significance
      of the circulating level of hepatocyte growth factor (HGF) as a tumor marker,
      especially in early-stage gastric cancer patients. METHODS: Preoperative serum
      HGF levels were measured with an enzyme-linked immunosorbent assay in 30 early
      stage and 42 advanced-stage gastric cancer patients. RESULTS: The mean value of
      serum HGF in 72 patients was significantly higher than that in the normal
      subjects. There was a significant increase in serum HGF levels in both advanced
      stage and early-stage patients compared with normal subjects. The positivity
      rates of HGF in early disease cases were higher than those of CEA and CA19-9. The
      serum HGF level was significantly higher in patients with vessel invasion than in
      those without invasion. In smaller early gastric cancers, serum HGF elevation was
      associated with lymphatic invasion. CONCLUSIONS: The serum HGF level may be a
      clinically significant tumor marker in patients with early-stage, as well as
      advanced-stage, gastric cancer. HGF elevation in early-stage patients may help us
      to predict the risk of lymph node metastasis of early gastric tumors, even of
      smaller tumor size. HGF may be a useful indicator for appropriate lymphadenectomy
      in early gastric cancer.

PMID- 15513371
TI  - A further comment.

PMID- 15513363
TI  - Prognostic relevance of 20q13 gains in sporadic colorectal cancers: a FISH
      analysis.
AB  - BACKGROUND: Amplification of 20q13 is a frequent chromosomal alteration in solid
      tumors and harbors a number of putative oncogenes (CAS/CSE1-L, NABC1, or
      Aurora2). Amplifications on 20q13 have been identified as an independent
      prognostic marker indicating worse survival in breast and ovarian cancer.
      However, little is known about the prognostic significance of 20q13 gains in
      sporadic colorectal cancers. The aim of this study was to correlate 20q13 gains
      in sporadic colorectal cancers with other known prognostic factors, tumor
      progression, and overall survival. METHODS: Nuclei were extracted from 146
      paraffin-embedded colorectal cancers of different UICC stages and used for
      fluorescence in situ hybridization (FISH) with a directly labeled probe for
      20q13.2 (VYSIS). Signals were counted in 120 nuclei per sample. 20q13 was
      considered gained when > or =40% of the nuclei showed 3 or more FISH signals.
      Statistical correlations were tested with log-rank tests and Kaplan-Meier
      survival curves. RESULTS: Signal numbers for 20q13.2 were gained in 78 cases
      (53%). Cases with gains on 20q13.2 showed worse outcome than cases without: the
      gain of 20q13.2 was an independent prognostic marker for overall survival
      (P=0.006) as well as tumor progression (P=0.012) in univariate and multivariate
      analyses. Gains on 20q13.2 did not correlate with tumor stage. However, there was
      a significant association between 20q13.2 gains and tumor location in the left
      sided colon and an inverse correlation between histologic grade and 20q13.2
      gains. CONCLUSION: These data indicate that gains on 20q13.2 correlate with
      faster tumor progression and worse patient survival independent from tumor size
      and lymph node involvement. Therefore, alterations on 20q13 are an important
      biological event in colorectal tumor progression with independent prognostic
      relevance.

PMID- 15513375
TI  - In response to Drs. Leon and Roy.

PMID- 15513365
TI  - Low-level hepatitis C viremia and humoral immune response to NS4 in chronic
      hepatitis B virus-hepatitis C virus coinfection.
AB  - BACKGROUND: There is a limited amount of published data on the interference of
      hepatitis B virus (HBV) on hepatitis C virus (HCV). The aim of this study was to
      investigate the effect of concurrent HBV infection on serum titers of HCV RNA and
      HCV antibody profiles in chronic HCV infection. METHODS: The clinical and
      virological profiles (serum titers of HCV RNA, HCV genotypes and antibody
      profiles) of 25 patients with chronic HBV-HCV coinfection were compared with
      those of 25 age- and sex-matched patients with HCV infection alone. RESULTS:
      Among the 25 patients with HBV-HCV coinfection, only 3 were found hepatitis Be
      antigen (HBeAg) and HBV DNA positive by hybridization assays, and the other 11
      were found HBV DNA positive by polymerase chain reaction. Genotype 1b was
      dominant in both HBV-HCV coinfection and HCV infection alone (64% versus 84%, P >
      0.1). Patients with HBV-HCV coinfection had significantly lower alanine
      aminotransferase (ALAT) levels and inflammatory scores but higher fibrosis scores
      than those with HCV infection alone. Serum titers of HCV RNA were significantly
      lower in HBV-HCV coinfection than in HCV infection alone. The frequency and
      relative intensity of antibody response to core, E2/NS1, NS3, and NS5 showed no
      significant difference between the two groups, but antibody response to NS4 was
      diminished significantly in HBV-HCV coinfection. CONCLUSIONS: In HBV-HCV
      coinfection, serum levels of HBV DNA are usually low or undetectable. Concurrent
      HBV infection, however, could interfere with HCV replication and suppress
      antibody response to NS4. The biological significance of selective inhibition of
      humoral immune response to NS4 in HBV-HCV coinfection should be further studied.

PMID- 15513368
TI  - A new index for resection of Meckel diverticula in children.

PMID- 15513372
TI  - A comment. Ferrous fumarate deteriorated plasma antioxidant status in patients
      with Crohn disease.

PMID- 15513359
TI  - Association between sigmoid diverticulitis and left-sided colon cancer: a nested,
      population-based, case control study.
AB  - BACKGROUND: An increased risk of left-sided colon cancer in patients with
      diverticular disease of the sigmoid colon has been reported. The aim of this
      study was to investigate to what extent patients with diverticulitis of the
      sigmoid colon differ in long-term risk of colon cancer compared to patients with
      diverticulosis of the colon without any clinical signs of diverticulitis.
      METHODS: A total of 7159 patients (2478 M, 4681 F) discharged with a diagnosis of
      diverticulosis or diverticulitis in 1965-83 in the Uppsala Health Care Region
      were followed-up with the Swedish Cancer Registry. Sixty-four cases with colon
      cancer were identified and compared with 123 controls without cancer matched for
      sex, age and year of first discharge. Based on information from the patients'
      charts, an independent observer blinded to the outcome assigned a clinical
      diagnosis of diverticulitis or not diverticulitis to cases and controls. RESULTS:
      In patients classified as having sigmoid diverticulitis there was an increased
      risk of left-sided colon cancer compared with patients with diverticulosis
      without any clinical signs of diverticulitis (odds ratio = 4.2, 95% CI 1.3-13.0)
      which remained after mutually adjusting for several clinical parameters in a
      multivariate conditional logistic regression analysis. CONCLUSION: The results of
      the study indicate a causal association between sigmoid diverticulitis and a long
      term increased risk of left-sided colon cancer.

PMID- 15513376
TI  - Screening for colorectal cancer in Europe.

PMID- 15513366
TI  - Rightward shift of colorectal cancer in Italy during the past three decades.

PMID- 15513373
TI  - CD7 and CD103 as markers for the clinical enumeration of small-bowel
      intraepithelial lymphocytes.

PMID- 15513370
TI  - Neuroendocrine differentiation of periodic-acid Schiff and Alcian blue-negative
      signet-ring cell-like cells and tubular adenocarcinoma cells within a gastric
      cancer.
AB  - A case of a Borrmann type 2 advanced gastric cancer with endocrine
      differentiation is described. Histologically, the cancer was either composed of
      cells arranged in a tubular pattern or formed solid nests of various sizes. The
      tubular pattern was composed of a moderately differentiated tubular
      adenocarcinoma. The histology showed partial carcinoid tumor-like features.
      Cancer cells inside solid nests had a signet-ring cell-like appearance. Periodic
      acid Schiff (PAS) staining was positive in the cytoplasm of a few of the cells
      found in the tubular pattern and in the mucus in some lumens and on the apical
      surface of cells in some lumens, but PAS did not stain cancer cells in the solid
      nests. Neither cancer cells nor mucus in the lumens were stained with alcian
      blue. All cancer cells were strongly positive for Grimelius silver stain, and
      most of the cancer cells stained positively for chromogranin A. Electron
      microscopic examination showed electron dense neuroendocrine granules in the
      cytoplasm of cancer cells. Cancer cells were stained positively for
      pancytokeratin, cytokeratin 8/18 and carcinoembryonic antigen. Muc 1 mucin
      glycoprotein staining was positive along the cell surfaces of cancer cells, but
      Muc 2, 5AC and 6 stainings were negative, although Muc 3 stained positively in
      the cytoplasm of a few cancer cells. The present case is a gastric tubular
      adenocarcinoma with Muc 1-positive, neutral- and acid mucin-negative signet-ring
      cell-like cells, which is associated with neuroendocrine differentiation.

PMID- 15513374
TI  - A response to Farup and Bytzer. Tegaserod Nordic trial.

PMID- 15513377
TI  - The G.U.T. of gut.

PMID- 15513387
TI  - Vitamins A and D but not E and K decreased the cell number in human pancreatic
      cancer cell lines.
AB  - BACKGROUND: The four fat-soluble vitamins A, D, E and K have been tested in
      experimental and human studies to assess their influence on the growth of cancer
      cells of different origins. Receptors for vitamin A and D have been detected on
      pancreatic cancer cells, and analogues of these reduced the cell number in vitro.
      The aim of the present study was to evaluate the effect of fat-soluble vitamins
      on the growth of pancreatic cancer cells. METHODS: The seven cell lines used were
      established from patients operated on for pancreatic adenocarcinoma. The effect
      of incubation with the vitamin A analogues all-trans-retinoic acid
      (atRA;tretinoin) and 9-cis-retinoic acid (9-cis-RA), the synthetic vitamin D
      analogue EB 1089, vitamin E succinate and K on the cell number was examined by
      the XTT method. RESULTS: The vitamin A and D analogues decreased the pancreatic
      cancer cell number when high concentrations of 10 - 10 M were administered. A
      combination of retinoids and the vitamin D analogue EB 1089 did not enhance the
      effect. Vitamin E succinate inhibited cell growth to a small extent (maximal 26%)
      in 3 out of 7 cell lines, whereas vitamin K increased the pancreatic cancer cell
      number in 3 out of 7 cell lines. CONCLUSION: High concentrations of vitamin A and
      D analogues decreased the cell number in pancreatic cancer cell lines. Vitamin E
      succinate and K did not have this effect. In the treatment of pancreatic cancer,
      further exploration of vitamin D analogues could be fruitful.

PMID- 15513383
TI  - Real-time PCR of host DNA in feces to study differential exfoliation of
      colonocytes between rats and humans.
AB  - BACKGROUND: Colonic mucosa has a high turnover rate. At the end of their
      lifespan, colonocytes become senescent and die. Histological studies indicate
      that senescent colonocytes are shed (exfoliated) into the fecal stream in rats,
      but phagocytosed by mucosal macrophages in humans. We study whether
      quantification of host DNA in feces can be used as a non-invasive marker for this
      differential disposal of colonocytes. METHODS: Selective primers and probes for
      the rat and human beta-globin genes were designed and used in real-time PCR
      reactions. RESULTS: Host DNA was quantitatively extracted and detected in fecal
      samples of both species. Feces of rats fed a humanized diet contained
      approximately 100 microg rat DNA per g freeze-dried feces. In human feces,
      however, only 5 out of 12 samples contained detectable, though very low (less
      than 0.35 microg/g), levels of host DNA. This about 300-fold difference could not
      be attributed to differences in DNase activities in the fecal stream. CONCLUSION:
      Our results indicate that there is considerable luminal shedding of senescent
      colonocytes in rats, whereas mucosal phagocytosis is the main route of colonocyte
      disposal in humans. Thus, real-time PCR of host DNA in feces can be applied as a
      non-invasive method for studying the differential exfoliation of colonocytes.

PMID- 15513382
TI  - Randomized study of biennial screening with a faecal occult blood test: results
      after nine screening rounds.
AB  - BACKGROUND: Two large true population studies in Europe have shown a significant
      reduction in mortality from colorectal cancer (CRC) by screening with a faecal
      occult blood test. In one trial conducted in Funen County, 61,933 individuals
      (aged 45-75 years) were randomly allocated either to a control group or to
      receive a biennial Hemoccult-II test. METHODS: These individuals were followed
      from 1985 to 2002 and 9 screening rounds were performed. RESULTS: First screening
      was accepted by 67% (20,672). Positivity rates varied between 0.8% and 3.8%, and
      the cumulative proportion of the test group having colonoscopy was 5.3%. Screen
      detected CRC was early (Dukes' A) in 36% compared to 11% among controls.
      Incidence of CRC was unchanged, but mortality was reduced by 11%. This figure
      increased to 43% in persons participating in all 9 rounds. No more than 8,558
      were screened at the 9th round. Patients with CRC detected between screenings had
      better survival than controls. Death rates from causes other than CRC among
      participants never became higher than among controls. CONCLUSION: The lesser
      reduction in mortality from CRC of 11% compared to 18% after 5 screening rounds
      may be explained by the decrease in the number screened. Efficacy in those
      screened supports the introduction of countrywide screening in Denmark, but it
      must be ascertained that acceptability, proportion of early CRC and logistics all
      reach the same standard as in the randomized trial.

PMID- 15513379
TI  - Does Helicobacter pylori infection explain all socio-economic differences in
      peptic ulcer incidence? Genetic and psychosocial markers for incident peptic
      ulcer disease in a large cohort of Danish adults.
AB  - BACKGROUND: Peptic ulcer epidemiology has changed considerably within the past
      century. The aim of this study was to assess the 11-year cumulative incidence of
      peptic ulcer disease and examine the relationship between ulcer incidence and
      psychosocial and genetic factors. METHODS: A random sample of 2416 Danish adults
      with no history of peptic ulcer disease residing in Copenhagen County, Denmark,
      attended a population-based prospective cohort study in 1983 and 1994. All
      participants reported whether they had had an ulcer diagnosed within the
      observation period. Information on socio-economic factors, family history of
      peptic ulcer disease (PUD) and lifestyle practices was obtained from a
      questionnaire. Lewis blood group antigens were assessed from blood samples and
      Helicobacter pylori infection status was determined with an in-house IgG ELISA.
      RESULTS: The overall 11-year cumulative incidence proportion of PUD was 2.9% (95%
      CI (2.2; 3.6)), i.e. 1.6% (95% CI (1.1; 2.1)) for duodenal ulcer, and 1.3% (95%
      CI (0.8; 1.7)) for gastric ulcer. Poor socio-economic status increased the risk
      of PUD independently of H. pylori infection (odds ratio 2.7, 95% CI (1.1; 6.1))
      and accounted for 17% of all ulcer cases. High physical activity at work
      increased the risk of PUD in people infected with H. pylori (odds ratio 2.6, 95%
      CI (0.8; 8.0)). Family history of PUD or Lewis blood group antigens did not
      relate to ulcer incidence. CONCLUSIONS: Poor socio-economic status is an
      important risk factor for PUD that exerts its effect independently of H. pylori
      infection. Strenuous work may increase the risk of PUD in people with H. pylori
      infection. Genetic factors do not influence the risk of PUD in Danish adults.

PMID- 15513381
TI  - Clinical characteristics of collagenous and lymphocytic colitis.
AB  - BACKGROUND: Microscopic colitides (MC), collagenous colitis (CC) and lymphocytic
      colitis (LC) share clinical features, but their mutual relationship is unclear,
      and clinical comparative studies are rare. We aimed to examine the clinical
      features in CC and LC by focusing on concomitant diseases. METHODS: Patients with
      MC (30 with CC, 54 with LC) were identified in the pathology databases and by
      reviewing biopsies. Controls included 84 age- and sex-matched persons. The
      clinical data collected from patient records were prospectively completed by
      interviews. RESULTS: The female:male ratio was 2:1 in CC and 5.75:1 in LC. Mean
      age at diagnosis was 53 in CC and 55.4 years in LC. There were no differences in
      the pattern of symptoms. Concomitant autoimmune diseases were more common in CC
      (53.3%) than in LC (25.9%; P = 0.017). Celiac disease was common in both CC (20%)
      and LC (14.8%). Bronchial asthma was associated with LC (25.9%), but not with CC
      (6.7%; P = 0.042). Colon diverticulosis was rare in MC (16%) compared with the
      controls (39%; P = 0.001). Hypolactasia was common in MC (45%; 76% in CC, 54% in
      LC) compared to its prevalence in the Finnish general population (17%).
      CONCLUSIONS: CC and LC are largely similar clinically, but the differences in the
      occurrence of autoimmune conditions and bronchial asthma suggest that they differ
      in immunopathogenesis. MC is associated with reduced lactose tolerance and shows
      a negative association with diverticular disease, possibly related to the small
      intestinal pathology and abnormal stool consistency.

PMID- 15513384
TI  - Long-term prognosis of patients with alcoholic liver cirrhosis: a 15-year follow
      up study of 100 Norwegian patients admitted to one unit.
AB  - BACKGROUND: Most follow-up studies in patients with alcoholic liver cirrhosis
      have been for a 5-year period or less. The aim of this study was to assess the
      long-term mortality and causes of death among patients with alcoholic liver
      cirrhosis and to identify predictors of mortality. METHODS: One hundred patients
      with alcoholic liver cirrhosis, consecutively admitted to one medical department,
      were included in the study from May 1984 until December 1988. All patients had a
      history of alcohol abuse of at least 100 g ethanol daily for several years. The
      study comprised 65 men and 35 women with a median age of 58 years (range 34-82).
      Percutaneous liver biopsies and/or autopsies were obtained on 89 patients. Sixty
      seven had ascites at admission and 34% had bleeding oesophageal varices. All
      patients were followed prospectively until death or until October 2000. RESULTS:
      During the follow-up period 90% of the patients died, 68 of whom (76 %) had been
      autopsied. The cumulative actuarial mortality after 1, 3, 6 and 12 months was
      18%, 28%, 36% and 49%, respectively and after 5, 10 and 15 years 71%, 84% and
      90%, respectively. None of the patients underwent liver transplantation during
      the study. The causes of death were bleeding, liver failure or a combination of
      these two conditions in 52 of 90 patients (58%), while 9 (11%) died of
      hepatocellular carcinoma 0.5 to 73 months after inclusion in the study. Using the
      Cox regression analysis, age, alcohol abuse and alkaline phosphatase were
      independent and significant predictors of mortality, but Child-Pugh class was
      not. CONCLUSIONS: The mortality in a group of patients with advanced alcoholic
      cirrhosis was extremely high with 5 and 15 years' mortality in 71% and 90%,
      respectively. Independent predictors of a poor prognosis were high age,
      continuous alcohol consumption of more than 10 g ethanol per day and high levels
      of alkaline phosphatase.

PMID- 15513385
TI  - High prevalence of metabolic complications in patients with non-alcoholic fatty
      liver disease.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is considered to be the
      liver component of the metabolic syndrome and is frequently associated with
      obesity, dyslipidemia and type II diabetes mellitus (NIDDM). We aimed to
      determine the development of liver function tests (LFTs) and metabolic
      complications in patients previously diagnosed with NAFLD. METHODS: One-hundred
      and-two patients with NAFLD diagnosed in the period 1994-2001 were identified.
      Eighty were brought in for new investigations, including LFTs, blood pressure,
      BMI, lipid profile, blood glucose and insulin. Original liver biopsy was re
      evaluated. RESULTS: Sixty-two patients (77%) were males (median age 46 years;
      mean follow-up time 2.8 +/- 1.2 years). Fifty-four patients (68%) were light to
      moderately overweight with body mass index (BMI) 25-30 kg/m. Mean BMI (28.2) was
      the same at diagnosis and at follow-up (28.3). At the new examination, 18
      patients (23%) had developed diabetes mellitus type II (n = 6) or had impaired
      fasting glucose (IFG) (n = 12), compared to only 2 patients at diagnosis.
      Hyperinsulinemia was observed in 19 patients (24%). Dyslipidemia, with elevated
      triglycerides and/or hypercholesterolemia, was now present in 65 patients (81%).
      Twenty-two patients (27%) had hypertension compared to 9 (11%) at diagnosis.
      Liver biopsy was performed in 24%, and 89% of those fulfilled the criteria for
      NASH. However, mild inflammation and fibrosis was observed, grade 1-2 (n = 17),
      stage I-II (n = 13) and none had cirrhosis. CONCLUSION: A significant proportion
      of patients with both clinical and histological diagnosis of NAFLD develop
      metabolic problems soon after diagnosis. These patients should be screened
      regularly for metabolic disorders.

PMID- 15513389
TI  - Incidence, management and recurrence rate of acute pancreatitis.
AB  - BACKGROUND: Acute pancreatitis is a common condition that is still associated
      with substantial morbidity and mortality rates. Management, outcome and
      recurrence rate in acute pancreatitis in a clinical setting using a conservative
      management approach are described. METHODS: A total of 1376 consecutive cases
      representing 2211 hospitalizations due to acute pancreatitis treated at the Dept.
      of Surgery, Lund University Hospital, Lund, were reviewed retrospectively.
      Management, outcome and recurrence rate were recorded. RESULTS: Incidence,
      including recurrences, was 300 per million per year; 21% of patients had
      recurrent (> or =2) attacks. In relapsing disease, two-thirds of patients had the
      first attack within 3 months. Mortality decreased over the period studied, but
      overall it was 4.2%; mortality in relapsing attacks was 2.5%, related to multiple
      organ dysfunction (MODS) in 67% and occurring within the first week in 36%.
      CONCLUSIONS: Despite a conservative approach in the management of acute
      pancreatitis, mortality is still substantial, frequently occurs early after
      admission, is associated with MODS and is also seen in relapsing disease. Early
      cholecystectomy and bile duct clearance could decrease recurrent attacks of
      biliary pancreatitis.

PMID- 15513390
TI  - The compact Erlangen Active Simulator for Interventional Endoscopy: a prospective
      comparison in structured team-training courses on "endoscopic hemostasis" for
      doctors and nurses to the "Endo-Trainer" model.
AB  - BACKGROUND: In 1997 Hochberger and Neumann presented the "Erlangen Biosimulation
      Model" (commercialized as the "Erlangen Endo-Trainer") at various national and
      international meetings. The new compactEASIE is a simplified version of the
      original "Biosimulation Model" (Endo-Trainer) and is specially designed for easy
      handling. CompactEASIE is reduced in its features, focusing exclusively on
      flexible endoscopy training. The acceptance of training in endoscopic hemostasis
      is accepted by workshop participants, as evaluated by a questionnaire on both
      models. METHODS: Eleven structured courses on endoscopic hemostasis for doctors
      and nurses organized by the same endoscopists from 3/1998 to 5/1999 were
      evaluated using one of both models. The questionnaires were filled in by 207/291
      trainees (71%). The Endo-Trainer was used in 4 (n = 103) and the compactEASIE in
      7 courses (n = 104). Both simulators were equipped with identical types of
      specially prepared pig-organ packages consisting of esophagus, stomach and
      duodenum, including artificial sewn-in vessels, polyps and varices. Blood
      perfusion was done with a roller pump connected to the sewn-in vessels and blood
      surrogate. All workshops were identical concerning the course structure: a 30-min
      theoretical introduction on ulcer bleeding was followed by 2 h of practical
      training in injection techniques and hemoclip application. The second part of
      variceal therapy consisted of a 30-min theoretical introduction prior to 2 h of
      practical training on sclerotherapy, band ligation and cyanoacrylate application.
      Finally, a questionnaire on the trainees' pre-experience and their rating of the
      different workshop sections was handed out to each participant. RESULTS: Previous
      endoscopic experience was comparable in both groups. The training in both
      simulators was highly accepted by the trainees (compactEASIE 95% excellent and
      good versus EASIE (Endo-Trainer) 97%) and did not show any significant difference
      (P = 0.493). Even in the assessment of the single techniques, no statistical
      difference was observed. Furthermore, the assessments of the closeness to reality
      and the endoscopic environment in both simulators were identical. CONCLUSIONS:
      Both simulators (Endo-Trainer, compactEASIE) are excellent educational tools for
      interventional endoscopy with a high level of acceptance. The easy-to-handle,
      "lightweight" compactEASIE is a significant, progress tool for the future.

PMID- 15513380
TI  - Endogenous heparin-like activity detected by anti-Xa assay in infected cirrhotic
      and non-cirrhotic patients.
AB  - BACKGROUND: Bacterial infections have been proposed as a trigger for portal
      hypertensive bleeding in cirrhotic patients. Endogenous low molecular weight
      heparinoids have been previously detected in vitro by heparinase-modified
      thromboelastography, but it is not known what type of heparinoids they are. The
      aim of this study was to assay anti-Xa concentrations to detect heparin activity
      in infected cirrhotics in vivo. METHODS: We evaluated 30 cirrhotic patients (15
      with bacterial infection, 15 not infected) and 9 non-cirrhotic patients with
      bacterial infection. The anti-Xa assay was performed at the start of infection in
      all patients and after resolution of infection in 8 cirrhotics (5 to 10 days
      after starting antibiotics); thromboelastography (native and heparinase I
      modified TEG) was performed in a subgroup of 11 cirrhotic patients with
      infection, 8 cirrhotics without infection and 8 non-cirrhotics with infection.
      RESULTS: Anti-Xa activity was detected in 9 of the 15 infected cirrhotics (60%)
      and only in 1 of 15 non-infected cirrhotics (6.7%) (P < 0.01). In the infected
      cirrhotic patients, a heparinase effect was shown in the heparinase I-modified
      TEG: k time (P < 0.01), alpha-angle (P < 0.01) and r time (P = 0.05), with no
      effect in the non-infected cirrhotics. Four of 9 (44%) infected non-cirrhotics
      were positive with the anti-Xa assay. CONCLUSION: In cirrhotic patients,
      bacterial infections modify haemostasis by producing endogenous heparin-like
      substances which can inhibit the activated clotting factor X (factor Xa). In
      infected non-cirrhotics, anti-Xa activity can also be found.

PMID- 15513391
TI  - Clinical characterization of patients with idiopathic chronic pancreatitis and
      SPINK1 Mutations.

PMID- 15513388
TI  - CCK-B receptor antagonist YF476 inhibits pancreatic enzyme secretion at a
      duodenal level in pigs.
AB  - BACKGROUND: To evaluate the mechanisms by which cholecystokinin (CCK) regulates
      the exocrine pancreas, the role and location of CCK receptors in the pig were
      investigated using the CCK-B receptor antagonist YF476 and different
      administration routes of CCK. METHODS: In 11 anaesthetized pigs, catheters were
      surgically implanted in the pancreatic duct for juice collection, and in the
      gastric arteries and jugular vein, so that infusions of CCK-33 could be directed
      to the duodenal/gastric, duodenal/pancreatic or general circulations,
      respectively. Experiments were performed under control conditions, and after
      pretreatment by gavage feeding with YF476, using either a single, low dose of 0.3
      micromol kg, which would block the CCK-B receptors, or a 1000 times higher dose
      (300 micromol kg), which would also block the CCK-A receptors. RESULTS: The
      increase in the pancreatic output of protein and the enzymes trypsin and amylase
      observed after the infusion of CCK-33 at 13 pmol kg to the duodenum/stomach or
      duodenum/pancreas was inhibited by pretreatment with YF476 at both dosages. In
      contrast, the increase in protein and enzyme output after the infusion of a
      supraphysiological dose of CCK-33 (130 pmol kg) to the general circulation was
      not affected by pretreatment with low dosage YF476, whereas high dosage YF476
      completely inhibited the stimulated secretion. CONCLUSIONS: These data indicate
      that CCK-33 given locally to the duodenum in doses raising CCK to physiological
      plasma levels stimulates the pancreatic enzyme secretion via duodenal CCK-B
      receptors. Supra-physiological doses of CCK-33 to the general circulation
      appeared to affect the pancreatic enzyme secretion via CCK-A receptors located
      elsewhere than in the pancreatic and duodenal tissue.

PMID- 15513393
TI  - Should we exclude individuals from endoscopy based exclusively on the absence of
      alarm symptoms?

PMID- 15513394
TI  - Outcome of Listeria monocytogenes prosthetic valve endocarditis: as bad as it
      looks?
AB  - In 1998 we presented 1 successfully treated case of Listeria monocytogenes
      prosthetic valve endocarditis and made a review of all the cases that had been
      published to date. We carry out an up-to-date review through Pub-Med of every
      case of Listeria monocytogenes prosthetic valve endocarditis; mortality rate is
      calculated and data from several clinical and therapeutical variables are
      collected; Fisher's exact test is used to identify those variables significantly
      associated with mortality. Four out of 23 patients died in hospital (17%); among
      all the variables included, only peripheral embolism (p=0.024), onset on a
      mechanical prosthesis (p=0.035) and having used only 1 antibiotic instead of a
      combination of drugs (p=0.026) were independently associated with mortality.
      Although the overall number of cases is too low to draw definite conclusions
      (n=23), mortality rate is lower than previously believed. Some variables that
      have traditionally been associated with a poor prognosis for endocarditides are
      not for the case of Listeria monocytogenes on valvular prostheses. It seems
      prudent to treat affected patients with a combination of ampicillin -- or
      vancomycin, if there is a history of beta-lactam allergy and ampicillin
      desensitization is not possible -- plus an aminoglycoside.

PMID- 15513392
TI  - Jejunal diverticulosis: a potentially dangerous entity.
AB  - Although jejunal diverticulosis is a rare entity and usually asymptomatic, it may
      cause chronic symptoms and acute complications. Because of the rarity of the
      entity, diagnosis is often delayed, resulting in unnecessary morbidity and
      mortality. The purpose of this study was to draw attention to jejunal diverticula
      and their complications. The medical records of 8 consecutive patients with
      complications due to small-bowel diverticula treated at our department during the
      past 4 years were reviewed. All diverticula were located in the jejunum. Seven
      patients had acute complications, 3 patients had an intra-abdominal abscess, 2
      had free perforation with diffuse peritonitis, 1 had a bowel occlusion and 1
      patient had concomitant bleeding and occlusion. One patient presented with
      chronic symptoms. A preoperative diagnosis of jejunal diverticula, before
      explorative laparotomy, was not reached in any of the 7 patients with acute
      symptoms. In the patient with chronic symptoms, multiple jejunal diverticula
      complicated by a jejuno-colic fistula and foreign body were found at laparotomy.
      On patient died of multiorgan failure. Small-bowel diverticulosis is a rare
      entity, but it should not be regarded as a clinically insignificant finding. It
      may be difficult to make a preoperative diagnosis. Patients with incidentally
      detected proximal jejunal diverticula, at imaging studies or at laparotomy,
      warrant close observation and awareness that the diverticula may cause serious
      complications.

PMID- 15513378
TI  - Interleukin-8 expression in the esophageal mucosa of patients with
      gastroesophageal reflux disease.
AB  - BACKGROUND: It has been reported that inflammatory cell infiltration can be
      detected in patients with endoscopically negative gastroesophageal reflux disease
      (GERD) as well as those with erosive reflux esophagitis. In this study, we
      examined the expression of mRNA for interleukin (IL)-8, a potent chemokine for
      neutrophils, in the esophageal mucosa of patients with GERD and compared the
      results with their endoscopic findings and symptoms. METHODS: Biopsy samples were
      obtained from 80 patients. Endoscopic diagnosis was performed according to the
      Los Angeles classification. Patients with typical symptoms such as heartburn
      despite normal endoscopic findings were classified as the non-erosive GERD group.
      Total cellular RNA was extracted from the biopsy samples and IL-8 mRNA was
      quantified by real-time polymerase chain reaction (PCR). Localization of IL-8
      protein in the esophageal mucosa was done by immunostaining. RESULTS: Expression
      of IL-8 mRNA was correlated with the endoscopic grade of esophagitis or with
      inflammatory cell infiltration, but not with the symptoms of the patients.
      Expression of IL-8 mRNA was also detected in all patients with non-erosive GERD.
      The level of IL-8 expression in non-erosive GERD was low compared with that in
      erosive GERD, but was higher than that in normal controls. IL-8 immunostaining
      was found in the basal layers of the esophageal mucosa. Administration of
      lansoprazole, a proton-pump inhibitor, decreased both IL-8 mRNA and protein
      levels in the esophageal mucosa. CONCLUSION: These results suggest that IL-8 in
      the esophageal mucosa may be involved in the pathogenesis of esophageal
      inflammation, including non-erosive GERD.

PMID- 15513398
TI  - The burden of infection with herpes simplex virus type 1 and type 2:
      seroprevalence study in Estonia.
AB  - Information on age- and gender-specific prevalence of herpes simplex virus (HSV)
      types 1 and 2 infections is crucial to guide genital herpes control strategies.
      Such data are not available from the newly independent Eastern European
      countries. We present of study of the age- and gender-specific prevalence of HSV
      1 and HSV-2 in low risk populations in Estonia. Serum samples from 1016 children,
      794 first trimester antenatal women, and 1036 blood donors (462M, 574F) were
      tested for HSV IgG antibodies by type-specific HSV-1 and HSV-2 assays. High
      seroprevalence rates of HSV-1 among children, pregnant women and (non-paid) blood
      donors were found. HSV-2 infection was not detected among boys. Gender
      differences in HSV-2 seroprevalence rates among people of reproductive age were
      observed: higher rates were recorded among pregnant women (23%) and female blood
      donors (21%), compared to 11% among male blood donors. HSV-1 seroprevalence was
      high in adults. HSV-2 seroprevalence was higher among females than males and
      increased substantially with age. HSV-2 prevalence in these non-high risk
      populations was relatively high, and may indicate a risk for an impending
      sexually- and STI- driven HIV epidemic.

PMID- 15513395
TI  - High versus standard dose vancomycin for osteomyelitis.
AB  - It is important to identify the optimal dosage and best method of infusion of
      parenteral vancomycin to be used over a several week period for the treatment of
      osteomyelitis. A retrospective study was undertaken to compare a high dose
      vancomycin treatment (HD: 40 mg/kg/d) with a standard dose treatment (SD: 20
      mg/kg/d), and also to compare the modality of infusion using either intermittent
      vancomycin infusion (IVI) or continuous vancomycin infusion (CVI). 89 patients
      with Gram-positive cocci osteomyelitis requiring vancomycin treatment were
      followed, and the outcome and therapeutic safety were compared. There were
      significantly more adverse drug reactions (acute renal failure) in the IVI
      subgroup (HD-IVI vs SD-IVI, p-value 0.007). No cases of renal failure were found
      in the HD-CVI subgroup. The best outcome was found in the subgroup of patients
      who received HD-CVI (HD-CVI vs SD-IVI, overall log rank p-value 0.02). HD-CVI
      treatment appears to provide an improved outcome with fewer adverse drug
      reactions.

PMID- 15513397
TI  - Use of ligase chain reaction for the rapid diagnosis of lymph node tuberculosis.
AB  - Ligase chain reaction amplification (LCx Abbott Laboratories) was used to detect
      the presence of M. tuberculosis in 101 adenopathy specimens obtained from 98
      patients. A total of 30 cases of lymph node tuberculosis were diagnosed, and the
      data were compared with results obtained using conventional techniques. The
      sensitivity of auramine staining and culture were 50.0% and 66.7%, respectively.
      The sensitivity, specificity, positive predictive value and negative predictive
      value of the LCx assay were 80.0, 98.6, 96.0, and 92.1% respectively. The results
      confirm the reliability of ligase chain reaction amplification for the detection
      of lymph node tuberculosis.

PMID- 15513399
TI  - Pivmecillinam and adverse birth and neonatal outcomes: a population-based cohort
      study.
AB  - A previous study unexpectedly showed an increased, statistically imprecise, risk
      of low Apgar score in children of women redeeming prescriptions for pivmecillinam
      in late pregnancy. To improve statistical precision we extended the previous
      dataset with data for 5 more y, and in addition added more neonatal outcomes. We
      thus examined the risk of adverse birth and neonatal outcomes among pregnant
      users of pivmecillinam based on population-based registries in North Jutland
      County, Denmark. We included 63,659 women with a live birth, or stillbirth after
      the 28th week of gestation. 2031 had redeemed prescriptions for pivmecillinam any
      time during pregnancy, 559 in the first trimester and 371 within 28 d before
      delivery. Adjusted odds ratios were: birth defects 0.83 (95% confidence interval
      (95% CI) 0.53-1.32) for exposure during first trimester, preterm delivery 0.96
      (95% CI 0.79-1.18) and low birth weight 0.79 (95% CI 0.52-1.20) for exposure any
      time during pregnancy, and stillbirth 1.19 (95% CI 0.30-4.80), low Apgar score
      1.17 (95% CI 0.37-3.66), hypoglycaemia 1.03 (95% CI 0.53-2.00), and respiratory
      distress syndrome 0.79 (95% CI 0.38-1.68) for exposure within 28 d before
      delivery. Use of pivmecillinam during pregnancy did not appear to increase the
      risk of adverse birth and neonatal outcomes; however, statistical precision is
      still low.

PMID- 15513386
TI  - Targeted inhibition of gene expression of pancreatitis-associated proteins
      exacerbates the severity of acute pancreatitis in rats.
AB  - BACKGROUND: Pancreatitis-associated protein (PAP) is a secretory protein not
      normally expressed in healthy pancreas but highly induced during acute
      pancreatitis. While PAP has been shown to be anti-bacterial and anti-apoptotic in
      vitro, its definitive biological function in vivo is not clear. METHODS: To
      elucidate the function of PAP, antisense oligodeoxyribonucleotides (AS-PAP)
      targeting all three isoforms of PAP were administered via intrapancreatic
      injections (5 mg kg day, 2 days) to rats prior to induction of pancreatitis.
      RESULTS: Severity of pancreatitis and cytokine gene expression in peripheral
      blood mononuclear cells (PBMC) were evaluated. Administration of AS-PAP, but not
      the scrambled oligodeoxyribonucleotide (SC-PAP) control, reduced pancreatitis
      induced PAP expression by 55.2 +/- 6.4%, 44.0 +/- 8.9%, and 38.9 +/- 10.7% for
      PAP isoforms I, II, and III, respectively, compared to saline-treated controls (P
      < 0.05 for all). Inhibition of PAP expression significantly worsened
      pancreatitis: serum amylase activity, pancreas wet weight (reflecting edema), and
      serum C-reactive protein levels all increased in AS-PAP-treated animals compared
      to SC-PAP-treated controls (by 3.5-, 1.7-, and 1.7-fold, respectively; P < 0.05
      for all). Histopathologic evaluation of pancreas revealed worsened edema,
      elevated leukocyte infiltration, and fat necrosis after AS-PAP treatment. Gene
      expressions of IL-1 microm and IL-4 were significantly higher in PBMC isolated
      from AS-PAP-treated rats compared to SC-PAP controls. CONCLUSION: This is the
      first in vivo evidence indicating that PAP mediates significant protection
      against pancreatic injury. Our data suggest that PAP may exert its protective
      function by suppressing local pancreatic as well as systemic inflammation during
      acute pancreatitis.

PMID- 15513402
TI  - Fluoroquinolone antibiotics in a hospital sewage line; occurrence, distribution
      and impact on bacterial resistance.
AB  - In hospital sewage lines, human faecal bacteria are exposed to antibiotics,
      posing a risk for selection of antibiotic resistant microorganisms. We
      constructed a system for continuous sampling in a hospital sewage line that
      allowed us to study longitudinal establishment of bacteria, concentrations of
      antibiotics, and selection of bacterial resistance in waste water, sediment and
      biofilm. The focus in this study was on fluoroquinolones, a widely used group of
      antibiotics with increasing resistance problems. We found low levels of
      ciprofloxacin and ofloxacin in waste water but high concentrations in sediment.
      Despite the high levels of fluoroquinolones bound to sediment, we did not find
      any development of resistance against fluoroquinolones in Enterobacteriacae spp.
      and faecal enterococci isolated from sediment.

PMID- 15513401
TI  - Clinical deterioration in community acquired infections associated with
      lymphocyte upsurge in immunocompetent hosts.
AB  - Clinical deterioration during the course of community-acquired infections can
      occur as a result of an exaggerated immune response of the host towards the
      inciting pathogens, leading to immune-mediated tissue damage. Whether a surge in
      the peripheral lymphocyte count can be used as a surrogate marker indicating the
      onset of immunopathological tissue damage is not known. In this study, we report
      the clinical presentations and outcomes of a cohort of immunocompetent patients
      with non-tuberculous community acquired infections who experienced clinical
      deterioration during hospital stay (n=85). 12 (14.1%) patients had a surge in
      lymphocyte count preceding their clinical deteriorations, and their diagnoses
      included viral pneumonitis , viral encephalitis , scrub typhus , leptospirosis ,
      brucellosis , and dengue haemorrhagic fever . The clinical manifestations during
      deterioration ranged from interstitial pneumonitis , airway obstruction , CNS
      disturbances , and systemic capillary leak syndrome , all of which were thought
      to represent immunopathological tissue damages. When compared with patients
      without lymphocyte surge, these patients were more likely to be infected with
      fastidious/viral pathogens (0 vs 12; p<0.05), in addition to having lower mean
      baseline lymphocyte counts (403+/-181 vs 1143+/-686 cells/microl; p<0.05). We
      postulate that the peripheral lymphocyte count may be a useful surrogate marker
      indicating the presence of immunopathological damage during clinical
      deterioration in certain infectious diseases.

PMID- 15513400
TI  - Low effectiveness of highly active antiretroviral therapy and high mortality in
      the Greenland HIV-infected population.
AB  - Greenland is a high-income country with free access to human immunodeficiency
      virus (HIV) care, including highly active antiretroviral therapy (HAART). We
      aimed to examine the HIV prevalence, age and gender distribution, and the
      effectiveness of HAART on CD4 positive cell count, viral load (VL), and mortality
      in the Greenland HIV-infected population. In this population-based cohort study
      we collected demographic, clinical and biochemical data on all HIV-infected
      patients followed in health clinics since 1995. For each case, we identified 100
      age- and gender-matched population controls. The HIV cohort included 103 patients
      of whom 91% were Inuit; 81% were infected heterosexually. Only 40% of the
      patients had a VL <400 copies/ml at 48 weeks after starting HAART, and patients
      on HAART had a substantial excess relative mortality compared with the general
      population (mortality rate ratio [MRR]: 10.6; 95% confidence interval [CI]: 6.9
      16.4). After the introduction of HAART, the mortality decreased (MRR: 2.5; 95% CI
      0.9-6.8), but remained high with a mortality rate of 62 per 1000 person-years
      (py) (95% CI 29-129). Our findings underline the difficulties of implementing
      successful HIV treatment even with unlimited economic resources and free access
      to health care.

PMID- 15513403
TI  - Severe pneumococcal meningitis heralding a deep hypogammaglobulinaemia related to
      common variable immunodeficiency, at the age of 27 years.
AB  - Common variable immunodeficiency with an associated broad immunoglobulin (0.7%)
      deficit affecting all subclasses, was revealed in a 27-y-old previously healthy
      female, upon development of a severe pneumococcal meningitis. We report the third
      case of purulent meningitis complicating this primary immunodeficiency, and the
      second due to Streptococcus pneumoniae. Clinicians should maintain an elevated
      suspicion for congenital immunodeficiency, especially when observing adult
      patients with a negligible prior history.

PMID- 15513404
TI  - Aspergillosis of the maxillary sinus: review and case report.
AB  - A case of non-invasive aspergillosis affecting the maxillary sinus is presented.
      Reference is made to its possible aetiology (spores introduced to the antrum at
      the time of a root canal overfilling with a zinc oxide paste). A review is
      presented and the management of the case is described.

PMID- 15513408
TI  - Falciparum malaria transmitted by a thick blood smear negative kidney donor.
AB  - This report describes a case of P. falciparum transmission by a recent-immigrant
      renal donor. The donor tested negative upon microscopy of a thick blood smear.
      The diagnosis was made after analysis of a Quantified Buffy Coat. In our opinion,
      a renal donor from a malaria endemic country should be pre-treated with
      antimalarials.

PMID- 15513396
TI  - Repetitive measurements of Chlamydia pneumoniae DNA in peripheral blood
      mononuclear cells in healthy control subjects and dialysis patients: a
      prospective study.
AB  - Infection with Chlamydia pneumoniae has been suggested to play a role in the
      development and maintenance of atherosclerosis. However, the course of C.
      pneumoniae infection is not clarified. Thus, both the persistence of C.
      pneumoniae DNA in blood and the tendency to recurrence have not been studied. We
      determined the prevalence of C. pneumoniae DNA in the white cells of the
      peripheral blood in 98 dialysis patients and in 52 healthy subjects. Blood
      samples were collected approximately 6 times from each subject during a period of
      1 y with an interval of approximately 2 months and analysed with a polymerase
      chain reaction. C. pneumoniae DNA was detectable in 47 out of 150 subjects at
      least once during a y. Reinfection was a rare phenomenon and the presence of C.
      pneumoniae DNA in blood was of less than 2 months' duration in almost all
      patients. There was a significant association between the presence of C.
      pneumoniae DNA during 1 y and the presence of atherosclerosis in the legs of
      dialysis patients (OR=3.50, p=0.03). Additionally, a significant association was
      found between the presence of C. pneumoniae DNA and an abnormal electrocardiogram
      (ECG) (OR=3.16, p=0.01). These findings may support the hypothesis of an
      association between infection with C. pneumoniae and the presence or development
      of atherosclerosis.

PMID- 15513405
TI  - Granulicatella (Abiotrophia) adiacens infection associated with a total knee
      arthroplasty.
AB  - We describe the first case of prosthetic joint associated infection due to
      Granulicatella adiacens (formerly Abiotrophia adiacens). Diagnosis was made by
      broad spectrum PCR, and later by culture. Diagnosis and treatment of this
      microorganism is difficult. Two y after revision and antibiotic treatment,
      infection was under control but not cured.

PMID- 15513410
TI  - Fatal transplacental infection with non-typhoidal Salmonella.
AB  - We report a case of transplacentally acquired neonatal sepsis with non-typhoid
      Salmonella. The infant's mother, a 36-y-old woman, presented with fever and
      malaise in the 25th week of gestation. Because of a pathological cardiotocogram,
      Caesarean section was performed a few h following admission. The premature infant
      had clinical signs of sepsis with multiorgan failure and died 4 d later despite
      intensive medical care. Maternal blood cultures and swab cultures taken from
      within the uterine cavity and from cutaneous and mucosal surfaces of the infant
      grew Salmonella virchow. This case and the few sporadic reports in the literature
      indicate that septicaemia due to non-typhoidal Salmonella spp. during pregnancy
      is highly lethal to the foetus or newborn, whereas prognosis for the mother
      apparently is excellent.

PMID- 15513409
TI  - Impact of prolonged treatment with trimethoprim-sulfamethoxazole on the human gut
      flora.
AB  - The case of a mentally ill man inadvertently treated with trimethoprim
      sulfamethoxazole (TMP-SMX) for 2 y is presented. Quantitative stool cultures
      revealed a substantially suppressed Gram-negative aerobic flora, while
      Enterococcus spp. and anaerobes were not affected. Yeasts were moderately
      increased. TMP-SMX represents an attractive antimicrobial for immunocompromized
      patients who need the integrity of their intestinal anaerobic flora for
      colonization resistance.

PMID- 15513406
TI  - A case of Legionnaires' disease with extensive concurrent deep vein thrombosis.
AB  - A previously healthy 37-y-old male presented with community-acquired pneumonia
      and extensive upper limb deep vein thrombosis. The diagnosis of Legionella
      pneumonia was made based on a positive direct immunofluorescence of the bronchial
      wash. An extensive investigation for hypercoagulable states was negative. The
      possible association between Legionella infection and deep vein thrombosis is
      highlighted.

PMID- 15513412
TI  - Acute hypersensitivity reaction to enfuvurtide upon re-challenge.

PMID- 15513411
TI  - Port-A catheter-associated Nocardia bacteremia detected by gallium inflammation
      scan: a case report and literature review.
AB  - Central venous catheter-associated Nocardia bacteremia is rarely reported. We
      present the case of a 48-y-old male with a history of advanced T-cell lymphoma
      who suffered from recurrent fever and persistent Gram-positive bacillus
      bacteremia. Port-A catheter-associated Nocardia bacteremia was diagnosed on the
      basis of the clinical response to removal of the catheter and the finding of
      increased gallium uptake, along with the Port-A catheter presented in the gallium
      inflammation scan.

PMID- 15513413
TI  - Is antimicrobial multiresistance to antibiotics in Cambodian HIV-positive
      children related to prior antiretroviral or tuberculosis chemotherapy?

PMID- 15513407
TI  - Successful treatment of pulmonary mucormycosis in an allogenic bone-marrow
      transplant recipient with combined medical and surgical therapy.
AB  - Mucormycosis is a rare, but severe, complication in allogenic bone-marrow
      recipients with a mortality rate of about 80%. Moreover, its incidence appears to
      have increased within the last decade. We report a case of pulmonary and nasal
      mucormycosis in a 55-y-old patient, which occurred 1 y after BMT. Treatment
      combining 4 months of amphotericin B, early surgical resection of infected tissue
      and discontinuation of immunosuppressive treatment allowed the cure of this mould
      infection.

PMID- 15513415
TI  - Consistency of DIAGNOdent instruments for clinical assessment of fissure caries.
AB  - DIAGNOdent (KaVo, Biberach, Germany) has shown high diagnostic accuracy and intra
      operator agreement for caries detection, both in vitro and in vivo. The aims of
      this study were to compare DIAGNOdent with visual examination (VI) and bitewing
      radiographs (BW) for clinical assessment of occlusal fissures, and to evaluate
      inter-device consistency of clinical recording using four different DIAGNOdent
      instruments; secondly, to correlate DIAGNOdent readings with microbial culture of
      the measured site. The subjects were young adults, the material comprising 34
      occlusal fissures, scheduled for restorative treatment at the Dental School
      Clinic of the University of Iceland. Two examiners conducted visual and
      radiographic assessments. One examiner measured each site with four DIAGNOdent
      instruments in random order. The fissure was then opened and lesion depth was
      classified on a 4-point scale. Bacterial samples were taken from the fissure
      before and after opening. Intra-operator agreement was high (r = 0.85-0.98).
      Inter-device correlation for the four DIAGNOdent instruments was significant in
      all cases (r = 0.81-0.92). However, a common cut-off point could not be
      determined. There was weak but significant correlation between DIAGNOdent
      readings and all three classes of lesion depth. Level of infection showed very
      weak correlation with the DIAGNOdent readings. It was concluded that DIAGNOdent
      is more reliable in detecting dentinal caries if a proper cut-off point is used
      than in indicating actual lesion depth. Readings from the different instruments
      were not directly comparable, however, owing to the lack of a common cut-off
      point.

PMID- 15513414
TI  - Patients referred to a specialist clinic because of suspected temporomandibular
      disorders: a survey of 3194 patients in respect of diagnoses, treatments, and
      treatment outcome.
AB  - The aims were to study the patient population at a temporomandibular disorders
      (TMD) specialist clinic over time, and to try to find variables of importance for
      treatment outcome. The material consisted of 3194 consecutive patients who were
      referred to the clinic and underwent a clinical examination during the period
      1995-2002. A number of patient and treatment-related variables that had been
      collected in an electronic database were analyzed retrospectively. The age and
      sex distribution of the present patient material was in line with several
      previous investigations of TMD patients. The mean age of both men and women was
      42 years, and there was a large preponderance of women. A vast majority of the
      patients responded positively, and in few visits, on traditional conservative
      treatment methods. In line with previous studies, no strong predictors for
      treatment outcome were found. However, the diagnoses of disk displacement without
      reduction, arthritis in TMJs, and myalgia in masticatory muscles were predictors
      for a significant improvement, while the diagnosis orofacial pain of unspecified
      origin predicted a poorer prognosis.

PMID- 15513428
TI  - Corneal triple procedure.
AB  - Corneal diseases subject to keratoplasty are often combined with a certain degree
      of cataract. Therefore, appropriate strategies for the management of cataract are
      mandatory. One strategy is a sequential procedure performing cataract surgery
      after keratoplasty. Though this procedure enables us to estimate IOL power
      accurately, there are several drawbacks including multiple procedures, slow
      visual rehabilitation and endothelial damage during cataract surgery. On the
      other hand, triple procedure, consisting of penetrating keratoplasty,
      extracapsular lens extraction and IOL implantation, has several advantages, such
      as single procedure, rapid visual rehabilitation and no additional endothelial
      trauma. How-ever, open sky procedure may be accompanied by uncontrollable
      vitreous pressure followed by posterior capsule rupture and difficulty of IOL
      implantation, while the worst outcome may be expulsive hemorrhage. Combined core
      vitrectomy preceding corneal trephination is contrived to solve this problem.
      This procedure is simply performed from a single sclerotomy 3.5-4.01 mm posterior
      to the corneal limbus with a vitreous cutter under the external pressure to the
      eye, and vitreous pressure is sufficiently lowered to allow the following
      procedures to be done very safely. Another problem with triple procedure is the
      calculation of IOL power. This problem is caused by unpredictable keratometer
      readings after keratoplasty. Several methods for calculating IOL power in triple
      procedure are also discussed.

PMID- 15513420
TI  - Associations between social and general health factors and symptoms related to
      temporomandibular disorders and bruxism in a population of 50-year-old subjects.
AB  - The aim of this epidemiological study was to examine associations between
      temporomandibular (TMD)-related problems and variables from three domains: (1)
      socio-economic attributes, (2) general health and health-related lifestyle, and
      (3) dental attitudes and behaviors. The overall response rate to a questionnaire
      mailed to the total population of 50-year-old subjects in two Swedish counties
      (8,888 individuals) was 71%. Among the 53 questions in the questionnaire, those
      related to social, general health, and health-related factors were used as
      independent variables in logistic regression models. Three TMD-related symptoms
      and reported bruxism were used as dependent variables. Impaired general health
      was the strongest risk factor for reported TMD symptoms. Along with female gender
      and dissatisfaction with dental care, impaired general health was significantly
      associated with all three TMD symptoms. A few more factors were associated with
      pain from the TMJ only. In comparison, reported bruxism showed more significant
      associations with the independent variables. In addition to the variables
      associated with TMD symptoms, being single, college/university education, and
      daily tobacco use were also significantly correlated with bruxism. Besides female
      gender, impaired general health, dissatisfaction with dental care, and a few
      social and health-related factors demonstrated significant associations with TMD
      symptoms and reported bruxism.

PMID- 15513419
TI  - Caries-preventive effect of sodium fluoride mouthrinses: a systematic review of
      controlled clinical trials.
AB  - The Swedish Council on Technology Assessment in Health Care launched a project
      group in 1999 to systematically review and evaluate the existing literature on
      different caries-preventive methods. The aim of this article was to report the
      findings concerning the caries-preventive effect of fluoride mouthrinses (FMRs)
      in various age groups, with special reference to background fluorides. A
      systematic search in electronic databases for literature published between 1966
      and August 2003 was conducted with the inclusion criteria of a randomized or
      controlled clinical trial, at least 2 years' follow-up, and caries increment in
      the permanent dentition (DeltaDMFS/T) as endpoint. Out of 174 articles originally
      identified, 62 met the inclusion criteria. These studies were assessed
      independently by at least two reviewers and scored A-C according to predetermined
      criteria for methodology and performance. The measure of effect was the prevented
      fraction (PF) expressed as percent. The level of evidence was based on 25
      articles. The results revealed limited evidence (evidence level 3) for the caries
      preventive effect (PF 29%) of daily or weekly sodium fluoride rinses compared
      with placebo in permanent teeth of schoolchildren and adolescents with no
      additional fluoride exposure and for a caries-preventive effect on root caries in
      older adults. Inconclusive evidence (evidence level 4) was found regarding the
      effect of FMRs in schoolchildren and adolescents exposed to additional fluoride
      sources such as daily use of fluoride toothpaste. No firm support for the use of
      FMRs was disclosed in a small number of studies designed for patients at caries
      risk. Furthermore, no association between the frequency of the rinses and
      prevented fraction or saved surfaces per year was found. In conclusion, this
      systematic review suggests that sodium fluoride mouthrinses may have an anti
      caries effect in children with limited background of fluoride exposure, while its
      additional effect in children with daily use of fluoride toothpaste could be
      questioned. The need for further clinical trials to elucidate the effect of FMRs
      in risk patients and older adults is emphasized.

PMID- 15513417
TI  - Dental fear and oral health and family characteristics of Finnish children.
AB  - OBJECTIVES: Our aim was to describe the occurrence of dental fear among Finnish
      children of different ages and to ascertain how oral health and family
      characteristics are associated with dental fear. METHODS: The subject groups were
      aged 3, 6, 9, 12, and 15 years in two middle-sized cities, and the 1474
      participants were distributed over fairly equal samples of each age. A
      questionnaire given to each child to be filled out at home enquired about social
      background, oral hygiene habits, diet, and dental fear. Oral health status was
      examined clinically and radiographically by two calibrated dentists. Multiple
      logistic regression analyses were performed for each age group in order to study
      the associations between dental fear and selected factors. RESULTS: Dental fear
      was higher among 12- and 15-year-old children than among the younger ones. Pain,
      drilling, and local anesthesia were reported to be the most frightening aspects.
      Excluding the 12-year-olds, children whose family members reported dental fear
      were more likely to report dental fear than children whose family members did not
      report dental fear. Six- and 12-year-olds who had experienced caries were more
      likely to report dental fear than were caries-free children. Among 6-year-olds,
      father's education modified the effect of a child's caries experience on child
      dental fear. Frequent intake of sugary items and a limit on eating candies to
      only one day per week were associated with higher dental fear. CONCLUSIONS: Fear
      of dental treatment is still fairly common among Finnish children, and the
      factors associated with it differ with the age of the child.

PMID- 15513427
TI  - Introduction.

PMID- 15513416
TI  - Some characteristics of 50/55-year-old individuals with various experience of
      destructive periodontal disease: a cross-sectional study.
AB  - OBJECTIVE: To analyze the association between subject characteristics and degree
      of destructive periodontal disease in a randomly selected sample of 50/55-year
      old individuals. METHODS: A randomized and geographically stratified (urban/rural
      districts) subject sample composed of dentate 50-year-old (n = 190) and 55-year
      old individuals (n = 359) from the county of Varmland, Sweden were examined. Data
      were collected through full mouth clinical and radiographic examinations and by
      the use of questionnaires. Based on the cumulative distribution of the
      individuals with respect to mean probing attachment loss (PAL), subgroups of
      subjects with the lowest (L20%) and highest (H20%) experience of PAL were
      identified. Similar classifications were made for never-smokers and current
      smokers. Correlation analyses and forward stepwise logistic regression models
      were performed. RESULTS: The subgroup with the most extensive PAL loss (H20%)
      included a significantly higher proportion of (i) males (60 vs 33%), (ii)
      subjects with low educational level (65 vs 41%), (iii) smokers (49 vs 15%), and
      had (iv) less favorable lifestyle characteristics than the subgroup with minimal
      experience of PAL loss (L20%). The same pattern of differences was observed when
      the analysis was restricted to never-smokers, with the addition of a
      significantly lower proportion of subjects living in urban areas (40 vs 69%) in
      the H20% compared to the L20% subgroup. The stepwise logistic regression analysis
      revealed that number of teeth and smoking habits were significant factors in the
      identification of individuals in the L20% subgroup. For the H20% subgroup, number
      of teeth, gender, number of cigarettes/day and lifestyle index were significant
      explanatory variables. CONCLUSION: Number of remaining teeth and smoking habits
      were identified as the main discriminating factors for classification of subjects
      with regard to degree of destructive periodontal disease.

PMID- 15513418
TI  - Intra-oral pattern of tooth and periodontal bone loss between the age of 50 and
      60 years. A longitudinal prospective study.
AB  - OBJECTIVE: In a 10-year prospective study we analyzed (i) the intra-oral pattern
      of and (ii) potential risk factors for tooth and periodontal bone loss in 50-year
      old individuals. METHODS: A randomized subject sample of 50-year-old inhabitants
      in the County of Varmland, Sweden, was examined at baseline and after 10 years.
      Data from full-mouth clinical and radiographic examinations and questionnaire
      surveys of 309 (72%) of the individuals who were dentate at baseline were
      available for analysis. Non-parametric tests and binary logistic multiple
      regression models were used for statistical analysis of the data. RESULTS: 4.1%
      of the 7,101 teeth present at baseline, distributed among 39% of the subjects,
      were lost during the 10-year interval. The incidence of tooth loss was highest
      among mandibular molars (7.5%) and lowest among canines (1.8%). The relative risk
      (RR) for tooth loss for endodontically compromised teeth was 4.1 and for
      furcation-involved molars 2.4-6.5, depending on tooth position. Logistic
      regression analysis identified baseline alveolar bone level (ABL), endodontic
      conditions, CPITN score (Community Periodontal Index of Treatment Needs), tooth
      position, caries, and educational level as risk factors for tooth loss. The
      overall mean 10-year ABL change was -0.54 mm (S.E. 0.01). On a tooth level the
      ABL change varied between -0.35 mm (mandibular molars) and -0.79 mm (mandibular
      incisors). Smokers experienced a greater (20-131% depending on tooth type) mean
      bone loss than non-smokers. The logistic regression model revealed that tooth
      position, smoking, and probing pocket depth > or =4 mm were risk factors for bone
      loss of >1 mm. No pertinent differences were observed with respect to risk
      factors for ABL change in the subgroup of non-smokers compared to the results of
      the analysis based on the entire subject sample. CONCLUSION: Tooth loss was more
      common in the molar than in the anterior tooth regions, while periodontal bone
      loss had a random distribution in the dentition. The predominant risk factors
      identified with regard to further radiographic bone loss were "probing pocket
      depth > or =6 mm" and "smoking".

PMID- 15513434
TI  - Results of epiretinal membrane removal combined with PEA and IOL.
AB  - We examined 558 eyes from 538 surgical cases of idiopathic epiretinal membrane
      with respect to the effectiveness of the triple surgery that involves concomitant
      intraocular lens surgery, the most appropriate timing for the evaluation of
      postoperative visual acuity, and the relationship between the pre- and
      postoperative visual acuity. From the viewpoint of the timing of the intraocular
      lens surgery, we classified our patients into 4 groups: (1) a phakic eye group;
      (2) a two-step surgery group; (3) a triple surgery group; and (4) an intraocular
      lens group. The visual acuity evaluation was performed in 22 eyes from the phakic
      eye group based on the patient's age being 45 years or younger, in all 326 eyes
      from the triple surgery group, and in all 86 eyes from the two-step surgery
      group. We excluded the intraocular lens group from the visual acuity evaluation.
      The timing of the visual acuity evaluation was one year after the surgery for the
      phakic eye and triple surgery groups, and one year after the intraocular lens
      surgery for the two-step surgery group. The postoperative visual acuity was
      correlated with the patient's age. When a patient was less than 55 years of age,
      the postoperative visual acuity correlated positively with age. In contrast, when
      a patient was 55 years of age or older, it correlated inversely with age. The
      postoperative visual acuity was significantly correlated with the preoperative
      visual acuity, and it was possible to predict the postoperative visual acuity
      based on a regression equation. The preoperative visual acuity necessary for a
      postoperative visual acuity of 20/20 or more was 20/20 for patients under 40
      years old, 20/40 for 40-59 years, 20/32 for 60-79 years, and 20/20 for 80 years
      and older.

PMID- 15513421
TI  - Effects of sagittal split ramus osteotomy on temporomandibular disorders in
      seventy-two patients.
AB  - Preoperative and postoperative temporomandibular disorders (TMDs) were observed
      in 72 patients before surgical-orthodontic treatment and about 2 years after
      bilateral sagittal split osteotomy. Prevalence and degree of TMD were assessed
      using the modified clinical dysfunction index of Helkimo. A total of 49 women and
      23 men (mean age 32 years) were included in the study. To find out which patients
      benefit most from the treatment, the sample was classified into subgroups-
      myogenous, arthrogenous, or both components of TMD. The prevalence of clicking
      and headache decreased significantly with the treatment, while the incidence of
      crepitation increased. In general, severity of the dysfunction was greatly
      reduced. Furthermore, multiple regression analysis showed that patients with
      excessive overjet and previous occlusal splint therapy benefit most from
      orthognathic treatment. In addition, patients with signs of mainly myogenous
      origin got more relief from their dysfunction than patients with mainly
      arthrogenous components of TMD. The results suggest that in patients with severe
      maxillomandibular discrepancy surgical-orthodontic therapy is a good choice of
      treatment for reducing myogenous TMD pain and discomfort.

PMID- 15513430
TI  - Combined surgery with deep lamellar keratoplasty.
AB  - The opportunity to perform two or more ophthalmic operations simultaneously has
      increased in recent years. In keratoplasty too, the simultaneous operation
      consisting of cataract extraction and IOL insertion (triple procedure) has become
      common. Penetrating keratoplasty (PKP) and planned extracapsular cataract
      extraction (PECCE) or vitrectomy is today often done simultaneously. However,
      phacoemulsification and aspiration (PEA) or 3 ports vitrectomy has to be
      performed on patients with corneal opacity due to some corneal diseases. In such
      cases, we performed the PEA or vitrectomy coupled with deep lamellar keratoplasty
      (DLK), successfully applied to closed eye surgery with corneal opacity.
      Simultaneous surgery using DLK, free of postoperative endothelial type of
      rejection, and PEA, enabling cataract extraction by a small incision, is a
      surgical technique making use of the advantage of the two types of operation. We
      performed the DLK + PEA + IOL on 17 cases. In the other hand, simultaneous
      surgery consisting of DLK and vitrectomy may be taken into consideration. The use
      of DLK will make it possible to perform surgery on urgent vitreoretinal diseases
      with corneal opacity and cataract. We performed the DLK + 3 ports vitrectomy on 3
      cases. The current study describes the advantages and disadvantages of these
      types of operation.

PMID- 15513429
TI  - Pars plana vitrectomy combined with penetrating keratoplasty.
AB  - Pars plana vitrectomy combined with keratoplasty using a temporary
      keratoprosthesis is a surgical procedure used in patients with vitreoretinal
      disorders complicated by severe corneal opacification. Temporary keratoprostheses
      include the Landers type and Eckardt type. Use of the Eckardt temporary
      keratoprosthesis is superior because of a wider optical diameter and easier
      visualization of the peripheral fundus. However, one problem with this procedure
      is that many patients develop postoperative rejection and loss of transparency of
      the corneal graft. To maintain good transparency of the corneal graft after
      surgery, vitrectomy must be minimally invasive and postoperative anti
      inflammation must be ensured.

PMID- 15513431
TI  - Advantage of combined procedure in vitreous surgery.
AB  - Lens preservation facilitates the progression of nuclear cataracts after vitreous
      surgery among patients over 45 years old, and postoperative nuclear cataracts
      frequently necessitate intraocular lens surgery. Once the lens is removed, the
      fundus from the posterior pole to the ciliary process becomes recognizable and
      surgically reachable, thus making total vitreous removal possible. The complete
      removal of the incarcerated vitreous to the scleral wound prevents postoperative
      vitreous base tears, and anterior hyaloidal fibrovascular proliferation.
      Simultaneous vitreous surgery plus intraocular lens surgery (triple surgery) will
      prevent these complications before they arise. Triple surgery for patients over
      45 years of age is reasonable even if they have amplitude of accommodation, and
      is an effective surgical strategy in that it improves both the result of the
      vitreous surgery and the patient's quality of life.

PMID- 15513433
TI  - Results of macular hole surgery combined with PEA and IOL.
AB  - We evaluated the factors affecting closure and postoperative visual acuity, as
      well as complications among idiopathic macular hole surgery cases comprising 631
      eyes in 576 patients. Almost all the surgeries were combined with simultaneous
      intraocular lens surgery (triple surgery). In some cases, the standard method was
      accompanied by internal limiting membrane peeling around the macular hole or
      abrasion of retinal pigment epithelium at the base of the macular holes. We found
      that male gender and short eye axial length were associated with closure and
      postoperative visual acuity. Although the frequency of peripheral retinal tears
      during surgery was high, the frequency of postoperative retinal detachment was
      less than 2%. The reopening frequency was about 5% among all cases, and was
      highest among eyes that underwent the abrasion method. There were no other
      significant complications. Internal limiting membrane peeling is effective for
      treatment of cases with unfavorable preoperative conditions. However, the
      standard method is sufficiently effective for cases with favorable preoperative
      conditions. Further analysis is required to evaluate postoperative visual
      function by methods other than visual acuity. Further study of internal limiting
      membrane peeling, as a treatment alternative, is also required.

PMID- 15513432
TI  - Combined procedures in glaucoma surgery.

PMID- 15513435
TI  - Surgically-induced astigmatism following single-site phacotrabeculectomy,
      phacotrabeculotomy and advanced non-penetrating phacotrabeculectomy.
AB  - We study surgically-induced astigmatism following three kinds of glaucoma
      surgeries combined with cataract surgery with 6 months of follow-up. The mean
      surgically-induced astigmatism at 6 months postoperatively was 1.92 +/- 1.87
      diopters in phacotrabeculectomy (n = 45), 0.72 +/- 0.40 diopters in advanced non
      penetrating phacotrabeculectomy (n = 40) and 0.76 +/- 0.47 diopters in
      phacotrabeculotomy (n = 49), which appeared to be stabilized by 3 months. Each
      group revealed a tendency of "with the wound" induced astigmatism.
      Phacotrabeculectomy could induce greater surgically-induced astigmatism than
      advanced non-penetrating phacotrabeculectomy and phacotrabeculotomy.

PMID- 15513436
TI  - Trabeculotomy combined with phacoemulsification and implantation of intraocular
      lens for primary open-angle glaucoma.
AB  - Retrospective study examined the surgical effects of lowering intraocular
      pressure of trabeculotomy combined with phacoemulsification and implantation of
      an intraocular lens. Included in the retrospective study were 96 eyes of 64
      patients with primary open-angle glaucoma. Preoperative mean IOP was 25.6 mmHg.
      At final examination, the IOP was well-controlled at 21 mmHg or lower without
      medications in 32 of 96 eyes. In another 62 eyes, the IOP was well-controlled
      with antiglaucoma medications. The postoperative IOPs were in the high teens
      after surgery. The life table analysis using Kaplan-Meier methods showed that the
      success probability after phacoemulsification and implantation of intraocular
      lens, combined with trabeculotomy (PIT)-I and PIT-II, were 93.9% and 82.6% at 4
      years, respectively. Postoperative visual acuity improved by more than two lines
      in 79 of the 96 eyes. In no case was the visual acuity decreased by more than two
      lines. Deterioration of the visual field was found in 4 eyes. There were no
      complications such as shallow anterior chamber, choroidal detachment, malignant
      glaucoma, hypotonic maculopathy, and endophthalmitis. This triple procedure
      should be performed in the early stages of glaucoma. Trabeculotomy is thought to
      relieve the resistance to aqueous outflow by mechanical cleavage of the
      trabecular meshwork and the inner layer of Schlemm's canal. This technique leads
      to aqueous outflow the from the opening of the internal trabecular meshwork to
      the collector channel. For this reason trabeculotomy was developed by a number of
      surgeons. Recently, however, trabeculotomy has not been selected for those
      patients with advanced stages of primary open-angle glaucoma because of the
      disadvantages such as transient intraocular pressure (IOP) elevation several days
      after surgery and somewhat higher levels (18 mmHg) of postoperative intraocular
      pressure (Fig. 1). To avoid the IOP spike (transient IOP elevation) after
      trabeculotomy, we reported previously that the new technique of trabeculotomy
      combined with outer sclerectomy was a useful surgical option. The results of our
      previous study indicated that the postoprative intraocular pressure levels after
      combined trabeculotomy and outer sclerectomy were significantly lower than that
      of trabeculotomy alone. On the other hand, trabeculotomy with mitomycin C is
      currently the standard filtration procedure for glaucoma. This technique, however
      causes severe postoperative complication such as hypotonic maculopathy, bleb
      leakage and late bleb infection. The major advantages of trabeculotomy preclude
      these severe complications resulting from creating progressive filtration of
      aqueous humor from the anterior chamber to the subconjunctival space. The recent
      advance of small-incision phacoemulsification procedure prompted
      phacoemulsification and implantation of intraocular lens and trabeculotomy. The
      theoretical advantages of smaller scleral, conjunctival incision, reduced stimuli
      to wound healing, and inflammation, could improve long-term IOP control in
      patients with glaucoma. Therefore several reports have been published on the
      surgical outcomes of combined trabeculotomy and modern phacoemulsification. These
      reports suggested that the combined trabeculotomy and a small-incision with
      intraocular lens implantation is effective in controlling IOP in patients with
      glaucoma.

PMID- 15513437
TI  - Trabeculectomy combined with phacoemulsification and intraocular lens
      implantation.
AB  - It has recently become popular to use mitomycin C (MMC) with trabeculectomy. MMC
      helps to maintain effective filtration and long-term intraocular pressure (IOP)
      control, while the use of laser suture lysis has improved the safety of this
      procedure. We evaluated the outcome of trabeculectomy alone and of trabeculectomy
      plus phacoemulsification (PEA) and intraocular lens (IOL) implantation, each
      supplemented with MMC. The mean preoperative IOP for the trabeculectomy alone
      group was 22.4 +/- 3.2 mmHg(bleb+), 25.3 +/- 2.6 mmHg(bleb-), and that of the
      combined surgery group was 22.4 +/- 2.8 mmHg(bleb+), 21.0 +/- 3.5 mmHg(bleb-).
      Mean postoperative IOP for the two groups were 13.3 +/- 2.7 mmHg(bleb+), 17.1 +/-
      4.4 mmHg(bleb-) and 11.9 +/- 2.7 mmHg(bleb+), 16.4 +/- 3.4 mmHg(bleb-),
      respectively. After 4.5 years, the success probability for postoperative IOP
      control was 38%(bleb+), 3%(bleb-) in the trabeculectomy alone group and
      53%(bleb+), 10%(bleb-) in the combined surgery group (<or=12 mmHg) and
      65%(bleb+), 3%(bleb-) and 75%(bleb+), 10%(bleb-) (<or=14 mmHg)(Kaplan-Meier
      survival rate). With early complications, the frequency of shallow anterior
      chamber and choroidal detachment were significantly fewer in the combined surgery
      group. The combined surgery of PEA, IOL implantation and trabeculectomy is an
      effective procedure that offers visual rehabilitation, fewer early complications
      and good IOP control in patients with advanced, medically uncontrolled glaucoma
      and cataract.

PMID- 15513439
TI  - Verteporfin therapy for choroidal neovascularization: from concept to proof of
      efficacy.

PMID- 15513438
TI  - Advanced nonpenetrating trabeculectomy (advanced NPT) and combined surgery of
      advanced NPT and phacoemulsification and intraocular lens implantation.
AB  - We have devised a new glaucoma surgery combining deep sclerectomy with
      nonpenetrating trabeculectomy (NPT); we call this surgery advanced NPT. We
      evaluated intraocular pressure (IOP) control, postoperative complication and
      visual acuity after combined advanced NPT and phacoemulsification and intraocular
      lens implantation (combined surgery), and advanced NPT alone. The mean
      preoperative IOP for the trabeculectomy only group was 22.4 +/- 6.3 mmHg(bleb+),
      23.0 +/- 4.9 mmHg(bleb-), and that of the combined surgery group was 18.1 +/- 4.5
      mmHg(bleb+), 18.5 +/- 2.6 mmHg(bleb-). Mean postoperative IOP for the two groups
      were 13.0 +/- 2.3 mmHg(bleb+), 15.0 +/- 1.5 mmHg(bleb-) and 12.9 +/- 2.7
      mmHg(bleb+), 13.3 +/- 2.4 mmHg(bleb-), respectively. After 15 months, the success
      probability for postoperative IOP control were 63%(bleb+), 23%(bleb-) in the
      advanced NPT only group (<or=12 mmHg), and 60% in the advanced NPT only group,
      70% in the combined surgery group (<or=14 mmHg) (Kaplan-Meier survival rate). In
      early complication, there were significantly fewer cases of shallow anterior
      chamber, hypertension, hypotension and anterior chamber inflamation in both
      groups than that of trabeculectomy. Nd:YAG goniopuncture was performed for
      purposes of better IOP control; preferred performance being within a month after
      surgery. Regarding visual acuity after either advanced NPT alone or combined
      surgery, an earlier recovery can be expected than with trabeculectomy. Advanced
      NPT and combined procedure is a reliable technique for glaucoma and cataract
      surgery.

PMID- 15513441
TI  - Photodynamic therapy with verteporfin: a new treatment in ophthalmology.
AB  - Photodynamic therapy (PDT) with verteporfin is a new treatment modality in
      ophthalmology that has previously shown its effectiveness in treatment of a
      variety of neoplastic pathologies. In this therapeutic approach, the
      photosensitizer verteporfin is activated by non-thermal laser light to obtain
      closure of neovascular structures. Preclinical and clinical studies have
      indicated that PDT is a safe, selective, and effective treatment for choroidal
      neovascularization in age-related macular degeneration. No significant damage to
      the neurosensory retina was found, which explains why PDT does not cause loss of
      visual acuity and may be used in a larger population than laser photocoagulation.
      This review summarizes the mechanisms of action of PDT, and the results of
      preclinical and clinical studies in ophthalmology.

PMID- 15513445
TI  - Photodynamic therapy with verteporfin following transpupillary thermotherapy for
      CNV evolving from an initially occult to a predominantly classic form, in
      patients with AMD.
AB  - The purpose of this paper is to evaluate photodynamic therapy (PDT) in the
      management of choroidal neovascularization (CNV) due to age-related macular
      degeneration (AMD) that converted from occult CNV to classic CNV after treatment
      with transpupillary thermotherapy (TTT). One hundred and fifty-four eyes of 130
      patients with symptomatic occult CNV were treated between June 2000 and August
      2001. We have analyzed data from patients treated with PDT because of a
      conversion from occult to classic CNV after TTT. The results were that twenty
      four of 154 eyes developed a predominantly classic CNV; 20 eyes of 19 consecutive
      patients were treated with PDT with verteporfin. The mean follow-up period was 10
      months. The mean delay for retreatment with TTT was 3 months; 3 eyes initially
      presented a pure occult CNV, 15 a minimally classic CNV, 1 an occult CNV with
      pigment epithelial detachment, and 1 a large macular subretinal hemorrhage with a
      subfoveal focal hot spot. The average classic component within a lesion before
      TTT was 20%. Recurrence of classic CNV was noted in the first 3 months for 14
      eyes. Visual acuity improved in 5 eyes by >/=2 lines, and in 2 eyes by 1 line; 4
      of 20 eyes had stabilized visual acuity; 7 eyes had a visual acuity decline of
      >/=2 lines; 2 eyes lost 1 line. All patients had reduction of metamorphopsia and
      reduction of exudation; 14 eyes had a little subretinal fibrosis and some
      partially atrophic areas; 6 eyes had slightly increased leakage in the late phase
      of the angiogram. In conclusion, association of TTT and PDT appears to be safe
      and may help practitioners to manage some difficult cases. This study seems to
      confirm the great efficacy of PDT in CNV with recent activity.

PMID- 15513440
TI  - Photodynamic therapy of age-related macular degeneration: History and principles.
AB  - We briefly review the history and principles of photodynamic therapy (PDT),
      especially as it is applied to choroidal neovascularization (CNV) in age-related
      macular degeneration (AMD). After a brief general history of PDT, we discuss the
      relationship between the physicochemical structure and photodynamic activity of
      the second-generation photosensitizers, such as those in current clinical use. We
      then discuss the basic photophysics of photosensitizer molecules, and describe
      the initial chemical reactions induced by activated sensitizers. We outline a
      novel method for screening photosensitizers to be used in treating CNV, as well
      as the complex biomolecular pathways modulated by PDT-induced oxidative stress
      and the vascular effects of PDT in solid tumors. The paper closes with a
      discussion of how all this information might be used to improve the selectivity
      and efficacy of clinically useful photosensitizers.

PMID- 15513446
TI  - Combining photodynamic therapy and feeder vessel photocoagulation: a pilot study.
AB  - Patients receiving photodynamic therapy (PDT) with verteporfin (Visudyne,
      Novartis AG), a new treatment for subfoveal choroidal neovascularization (CNV)
      secondary to age-related macular degeneration (AMD) and pathologic myopia, should
      be scheduled for follow-up every 12 weeks (+/-2 weeks) after the initial
      treatment. However, important data from clinical practice and from small series
      studies suggest that this period between treatment may be too long for some
      patients. In this pilot study we explore the safety and the possibility of
      improving the extent and duration of PDT benefit using feeder vessel treatment
      (FVT). This study suggests that the combination of verteporfin therapy and FVT is
      a safe procedure; it also suggests a possibility for prolonging the effect of
      verteporfin therapy.

PMID- 15513448
TI  - Treatment of optic neuropathy, has its time come?

PMID- 15513444
TI  - Cost of care for patients with age-related macular degeneration in Switzerland
      and cost-effectiveness of treatment with verteporfin therapy.
AB  - The cost-effectiveness of photodynamic therapy with verteporfin in the treatment
      of patients with predominantly classic subfoveal choroidal neovascularization
      secondary to age-related macular degeneration was investigated by a Markov Model
      over a time horizon of three years in Switzerland. This model describes patients
      moving between three levels of visual acuity (e.g., good vision, impaired vision,
      highly impaired vision) and death in terms of transition probabilities.
      Transition probabilities as well as effectiveness values were derived from a
      randomized, controlled, double-masked clinical trial. Effectiveness for
      verteporfin therapy and for placebo was calculated in terms of vision years:
      1.068 and 0.494, respectively. Cost per level of visual acuity was assessed in
      ascending order by expert panels from a societal perspective. Cost strongly
      increased parallel with vision loss on a patient-per-year basis from 4683 CHF at
      good vision to 8443 CHF at impaired vision, and was highest with 15231 CHF at
      highly impaired vision. The model-calculated cost per visionyear were 14907 CHF
      for patients in the verteporfin therapy group, versus 21047 CHF for patients in
      the placebo group. The incremental cost per vision-year additionally saved
      through verteporfin therapy was 9624 CHF. The study demonstrated that greater
      effectiveness of verteporfin therapy versus placebo compensated for the cost of
      the therapy so that verteporfin therapy was clearly costeffective. Therefore, for
      the indicated patients with AMD that causes severe vision loss, verteporfin
      therapy can be recommended as the therapy of choice, on both clinical and
      economic grounds.

PMID- 15513442
TI  - Verteporfin therapy for subfoveal choroidal neovascularization in age-related
      macular degeneration: from clinical trials to clinical practice.
AB  - People with choroidal neovascularization (CNV) due to age-related macular
      degeneration (AMD) are at high risk of central vision loss. Until verteporfin
      therapy became available, there was no safe and effective treatment for a large
      majority of these people. The phase III clinical trials of verteporfin therapy
      showed that treatment could safely reduce the risk of vision loss in the majority
      of patients presenting with either predominantly classic CNV or with occult with
      no classic CNV, and in selected patients with minimally classic CNV. The decision
      to treat patients with subfoveal CNV due to AMD using verteporfin therapy,
      requires an understanding of the outcomes of these clinical trials and of
      published guidelines. This review presents the key findings of the trials and
      outlines the factors that should be considered in clinical practice when deciding
      whether verteporfin therapy is indicated.

PMID- 15513443
TI  - Development of verteporfin therapy: a collaboration between pharmaceutical
      companies, device manufacturers and clinical investigators.
AB  - The potential for photodynamic therapy to provide new treatment options for
      patients with choroidal neovascularization has been of interest to
      ophthalmologists for many years. Verteporfin (Visudyne, Novartis AG) is the first
      photodynamic drug to receive regulatory approval for use in ophthalmology. The
      development of verteporfin therapy was more complex than that of many other drugs
      because of the need to develop both the light-activated drug and the laser system
      used to activate it. This article provides an overview of the development of
      verteporfin therapy, focussing on the contributions of the pharmaceutical
      companies, device manufacturers, and investigators who were involved in the
      program.

PMID- 15513450
TI  - Infectious optic neuropathy.
AB  - A wide variety of infectious agents are known to cause optic neuropathy. This
      article will consider the bacteria, spirochetes, fungi, and viruses that most
      commonly affect the optic nerve. Clinical presentation is variable, but some
      pathogens often produce a characteristic funduscopic pattern. Diagnosis is
      usually made on the basis of clinical suspicion and serologic testing. Polymerase
      chain reaction is also increasingly utilized. Most infectious agents can be
      effectively treated but visual recovery is highly variable.

PMID- 15513451
TI  - Dysthyroid optic neuropathy (DON).
AB  - Dysthyroid Optic Neuropathy (DON) affects a small percentage of patients with
      Graves disease, but, when it occurs, it can cause significant and permanent loss
      of vision. DON is treatable if recognized early. Systemic steroids can be
      effective, but may cause side affects. Orbital injection of steroids may play a
      role in selected patients. Orbital radiation has a more permanent effect and has
      gained wide acceptance as a relatively non-invasive method of reversing DON.
      Surgery to decompress crowded orbits has been used for years and continues to be
      a viable approach for those patients with optic neuropathy, especially when there
      is significant proptosis. Optic nerve decompression can also be achieved through
      a transethmoidal approach.

PMID- 15513455
TI  - Treatment of ischemic optic neuropathy.
AB  - Ischemic damage of the optic nerve has no proven effective treatment. While
      ischemia related to vasculitis (arteritic) is treated with systemic
      corticosteroids, the primary goal is to prevent further damage, either in the
      affected or fellow eye. Thrombolytic or anticoagulation supplementive therapy may
      be considerations for the future. In the more common idiopathic (nonarteritic)
      form (NAION), multiple attempts at therapy, including systemic corticosteroids,
      anticoagulants and antiplatelet agents, diphenylhydantoin, hyperbaric oxygen, and
      optic nerve sheath decompression have been unsuccessful. The use of levodopa has
      been proposed but is unproven. Megadose intravenous corticosteroid therapy has
      not been studied in a systematic way. Neuroprotective strategies are under
      intense investigation for optic neuropathies including NAION, and clinical trials
      in humans are in progress. Optic nerve regeneration studies are ongoing in
      animals. Prophylaxis in NAION is unproven.

PMID- 15513452
TI  - Treatment of tumors involving the optic nerves and chiasm.
AB  - An approach toward treatment of tumors involving the optic apparatus is
      presented. When tumors cause mass effect, microsurgical excision or debulking is
      generally recommended. Radiosurgery has been controversial yet advances in
      imaging and high speed computer planning allow treatment of lesions involving the
      optic apparatus with low morbidity. Microsurgical and radiosurgical approaches to
      tumors involving the globe, orbit, suprasellar region and third ventricle are
      discussed. Gamma Knife radiosurgery for choroidal melanomas spares orbital
      excenteration. We have used a marginal dose of 2025 Gy for choroidal melanomas
      and generally limit the optic nerves and chiasm to less than 10 Gy in other
      cases. The effective dose for cavernous hemangiomas remains unclear, however we
      have had success with marginal doses in the range of 1620Gy. Lower doses may
      prove successful yet better spare vision in cases where vision is useful. Our
      combined microsurgical and radiosurgical approach to tumors involving the
      apparatus has had an excellent rate of sparing vision, a low overall morbidity
      and excellent success.

PMID- 15513453
TI  - Metabolic optic neuropathies.
AB  - Metabolic optic neuropathies form a rubric of disease characterized by
      bilaterally symmetrical visual impairment with loss of central visual acuity,
      dyschromatopsia, centrocecal visual field defects, temporal optic disc atrophy,
      and specific loss of the nerve fiber layer in the papillomacular bundle. The
      three subcategories of metabolic optic neuropathies are heredodegenerative (such
      as Leber's hereditary optic neuropathy), nutritional deficiencies (such as
      vitamins B12 or folic acid), or toxicities (such as ethambutol or cyanide). It's
      interesting to note that the first of these three is a congenital cause of
      mitochondrial impairment, whereas the latter two are acquired injuries to
      mitochondria. Hence, most if not all causes of metabolic optic neuropathies are,
      in fact, related to mitochondrial impairment. At the present time there is no
      effective treatment for heredodegenerative optic neuropathy. Nutritional
      deficiency metabolic optic neuropathies are treated by giving supplements of the
      appropriate nutrient or vitamin, whereas toxic metabolic optic neuropathies are
      treated by removing or preventing exposure to the toxin in question.

PMID- 15513449
TI  - Treatment of acute demyelinating optic neuritis.
AB  - Patients with typical acute monosymptomatic demyelinating optic neuritis should
      receive gadolinium-enhanced magnetic resonance imaging (MRI) of the brain and
      orbits to determine if they are at high risk for the subsequent development of
      clinically definite multiple sclerosis (CDMS). The presence of >or=2 white matter
      lesions (>or=3 mm in diameter, at least 1 lesion periventricular or ovoid)
      indicates high risk for CDMS; the following treatment should be considered for
      such patients: 1. Intravenous methylprednisolone sodium succinate (1 gram IV/day
      for 3 days) followed by oral prednisone (1 mg/kg/day for 11 days) with 4-day
      taper (20 mg on day 1, 10 mg on days 2 and 4); 2. Interferon beta 1-a (Avonex
      30microg intramuscularly [IM] weekly, or Rebif 22 microg subcutaneously [SQ]
      weekly). These two drugs have been shown to reduce the short-term risk of CDMS in
      high risk monosymptomatic patients. In monosymptomatic patients with <2 white
      matter lesions, and in patients for whom CDMS has been established, IV
      methylprednisolone treatment followed by oral prednisone should be considered on
      an individual basis. Treatment in these patients may hasten visual recovery, but
      does not affect long-term visual outcome. Oral prednisone alone, without prior
      treatment with IV methylprednisolone, may increase the risk for recurrent optic
      neuritis and should be avoided.

PMID- 15513454
TI  - Treatment of Leber's hereditary optic neuropathy: theory to practice.
AB  - Dramatic advances in our understanding of the molecular genetic basis of Leber's
      hereditary optic neuropathy (LHON) have revolutionized our ability to diagnose
      and prognosticate this disease. Unfortunately no corresponding advances in the
      treatment of LHON have emerged. Glaucoma is a prevalent form of optic neuropathy
      that has been studied extensively. Lessons learned from treatment of LHON and
      glaucoma may have important implications for both diseases. LHON presents
      formidable challenges to the design and conduct of clinical trials. The acutely
      symptomatic LHON patient with monocular vision loss provides a unique clinical
      situation in which to test an agent during a critical therapeutic window.
      Advances in neuroprotection, apoptosis, and neurodegenerative diseases may
      provide important clues for potential therapeutic agents for LHON. Antioxidants
      and agents that interfere with the critical steps of mitochondrial-dependent,
      oxidative stress-induced apoptosis are candidates for future LHON therapy. A
      variety of neuroprotective agents, under active investigation in other diseases,
      may be useful in LHON therapy. Effective pharmacotherapy will complement the
      current management approach that has changed little in the 130 years since LHON
      was originally described.

PMID- 15513461
TI  - Laser surgery for angle closure glaucoma.
AB  - The angle closure glaucomas are defined by iridotrabecular contact, trabecular
      dysfunction, and elevated intraocular pressure (IOP). Laser iridotomy
      successfully eliminates the relative pupillary block component of the angle
      closure process, regardless of whether the underlying angle closure is related
      primarily to pupillary block or another mechanism. For those eyes with angle
      closure originating at an anatomic level posterior to the iris, such as plateau
      iris, lens-induced angle closure, or posterior segment processes, argon laser
      peripheral iridoplasty is often useful to further open the angle. The purpose of
      this article is to review the indications and techniques for laser iridotomy and
      laser iridoplasty in clinical practice.

PMID- 15513458
TI  - Gonioscopy in primary angle closure glaucoma.
AB  - Primary angle closure is a condition characterized by obstruction to aqueous
      humor outflow by the peripheral iris, and results in changes in the iridocorneal
      angle that are visible through gonioscopic examination. Gonioscopy in these eyes,
      however, can be difficult. This chapter discusses techniques that might help in
      the examination. These include beginning the examination with the inferior angle,
      methods to help in looking over the iris, cycloplegia, locating the corneal
      wedge, indentation, van Herick estimation, examining the other eye, and topical
      glycerin. Finally, there is a discussion about the pathology associated with the
      closed angle, with emphasis on the appearance of iris bombe, plateau iris, and
      the distinction between iris processes and peripheral anterior synechiae.

PMID- 15513457
TI  - The epidemiology of primary angle closure and associated glaucomatous optic
      neuropathy.
AB  - Angle closure glaucoma is emerging as a leading cause of blindness in the densely
      populated countries of Asia. It has a greater propensity to cause bilateral
      blindness than either primary open-angle glaucoma or secondary glaucoma. An
      estimated 9.4 million people in China aged 40 years and older have glaucomatous
      optic neuropathy. Approximately 5.2 million people (55%) would be blind in at
      least one eye. Around 1.7 million (18.1%) would be blind in both eyes. it is
      likely that PACG is responsible for the vast majority (91%) of bilateral glaucoma
      blindness in China. The number of Chinese people with an "occludable" drainage
      angle is in the region of 28.2 million, and of these 9.1 million have significant
      angle closure. There is a growing emphasis on a revised method of classifying the
      disease, which reserves the term "glaucoma" for cases with glaucomatous optic
      neuropathy. The term primary angle closure (PAC) is used in cases with a closed
      angle and peripheral anterior synechiae or raised intraocular pressure. Risk
      factors for PAC include older age, female gender, Chinese ethnicity, all of which
      are associated with anatomical risk factors of central and/or peripherally
      shallow anterior chambers (usually associated with a thicker, anteriorly
      positioned lens), and a shorter axial length of the globe.

PMID- 15513459
TI  - Angle closure: classification, concepts, and the role of ultrasound biomicroscopy
      in diagnosis and treatment.
AB  - The angle closure glaucomas are a diverse group of disorders characterized by
      mechanical blockage of the trabecular meshwork by the peripheral iris leading to
      elevated intraocular pressure and glaucoma. Understanding the pathophysiologic
      mechanisms underlying these disorders is essential for both diagnosis and
      management. This review covers the anatomy, etiology, classification, and therapy
      of the various angle closure glaucomas and the role that ultrasound biomicroscopy
      has played in helping us understand these diseases.

PMID- 15513460
TI  - Medical management of angle closure glaucoma.
AB  - Management of angle closure glaucoma requires an understanding of the underlying
      pathophysiologic mechanisms. Treatment is aimed at eliminating pupillary block
      and other causes of angle closure, re-opening the angle, and preventing further
      damage to the optic nerve by lowering intraocular pressure. Medical therapy plays
      an important role in the successful management of this condition. This article
      describes commonly used pharmacologic agents, as well as newer classes of drugs
      such as topical carbonic anhydrase inhibitors, prostaglandin analogues and
      selective alpha2- adrenergic agonists. Use of these drugs in several clinically
      distinct angle closure syndromes and modes of presentation are discussed.

PMID- 15513462
TI  - Incisional surgery for angle closure glaucoma.
AB  - Angle closure glaucoma remains a major challenge for ophthalmologists. The three
      main challenges in the treatment of angle closure glaucoma are, firstly, to
      achieve rapid reduction of intraocular pressure in acute angle closure glaucoma,
      secondly, to prevent progression to chronic angle closure glaucoma, and thirdly,
      to manage established chronic angle closure glaucoma. Incisional surgery for
      angle closure glaucoma is typically required when laser surgery and/or medical
      therapy fail to control the intraocular pressure or control progressive synechial
      closure. The role for surgical iridectomy and emergency trabeculectomy in the
      modern management of acute angle closure glaucoma is diminishing. Trabeculectomy,
      goniosynechialysis, cyclodestructive procedures, and glaucoma implant are
      effective surgical options for chronic angle closure glaucoma, but none of them
      have been shown to be more effective than the others with proper comparative
      clinical trials. Trabeculectomy and goniosynechialysis are often combined with
      cataract extraction, which appears to offer additional pressure-control benefits
      to patients with chronic angle closure glaucoma.

PMID- 15513468
TI  - Retinal complications of phakic intraocular lenses.
AB  - High myopia has always been a challenge for refractive correction. Current laser
      surgical techniques, however, fall short of correcting high refractive errors due
      to lack of predictability, regression, corneal ectasia, and introduction of high
      order optical aberration. Phakic intraocular lenses (IOL) have been proposed as
      an effective refractive surgical procedure for the correction of severe myopia,
      but, despite recent advances in implant material technology and design, their
      concept is still under clinical investigation. Most of the concern regarding the
      complications of phakic IOLs focuses on the anterior segment of the eye. This
      review examines the posterior segment complications associated with phakic IOL
      implantation, evaluates possible pathogenetic mechanisms and discusses posterior
      segment complications, prevention and management.

PMID- 15513469
TI  - Cataract surgery and diabetic retinopathy.
AB  - Diabetes is a risk factor for the development of cataracts. Studies have shown an
      increased risk of ocular complications in diabetics after cataract surgery, but
      modern surgical techniques have minimized them, leading to an overall good visual
      outcome. Macular edema before surgery is the most common condition that limits
      post-operative visual recovery. Thus, pre-operative laser treatment is needed.
      Photocoagulation of preproliferative or early proliferative diabetic retinopathy
      is also advisable, due to the increased risk of iris neovascularization or
      retinopathy progression after surgery.

PMID- 15513470
TI  - Current management strategies of acute post-operative endophthalmitis.
AB  - The current management of acute post-operative endophthalmitis relies on
      microbial confirmation, intravitreal antibiotics, and vitrectomy. The
      endophthalmitis vitrectomy study (EVS) demonstrated that systemic antibiotics are
      not necessary in post-cataract/secondary intraocular lens (IOL) acute bacterial
      endophthalmitis, and that vitrectomy could be required only for eyes with
      presenting vision of light perception. Since the publication of the EVS newer
      tests are available for microbial confirmation, and many new and effective
      antibiotics are discovered for systemic therapy. We have studied large numbers of
      patients with endophthalmitis over several years. Perhaps our experience
      represents the endophthalmitis status in the developing countries. The article is
      a synthesis of recent publications in the world literature. Finally the authors
      have suggested a management strategy for acute post-cataract acute bacterial
      endophthalmitis.

PMID- 15513471
TI  - Pars plana vitrectomy for refractory diabetic macular edema.
AB  - OBJECTIVE: The aim of this study is to describe the results of pars plana
      vitrectomy (PPV) for refractory diabetic macular edema (DME). METHODS: Review of
      the relevant peer-reviewed scientific literature identified using Medline. MAIN
      OUTCOME MEASURES: The anatomical and functional outcome of surgery. RESULTS:
      Vitrectomy with or without internal limiting membrane (ILM) peeling can be
      beneficial for the treatment of DME that is resistant to laser photocoagulation
      or sub-Tenon's steroid injection. Visual improvement has been reported in
      approximately 40-90% of patients, with approximately 85-100% experiencing either
      improvement or stabilization of vision. Retinal edema decreases or resolves in
      approximately 70-100% of patients. Complications range in severity with
      approximately 5-20% of patients developing peripheral retinal breaks,
      approximately 1-2% developing retinal detachment, approximately 2% developing
      macular hole, and approximately 10-60% developing cataract. Severe complications
      such as rubeosis iridis and the fibrinoid syndrome have also been reported.
      CONCLUSION: Pars plana vitrectomy can be an effective treatment for diabetic
      macular edema refractory to laser therapy and/or sub-Tenon's capsule steroid
      injection.

PMID- 15513472
TI  - Use of viscodissection and silicone oil in vitrectomy for severe diabetic
      retinopathy.
AB  - Improvement in surgical techniques has led to improved anatomic and functional
      success rates following surgery for severe complications of proliferative
      diabetic retinopathy (PDR). We compared the anatomic and functional outcomes of
      surgery in a non-randomized, consecutive case series of patients with severe PDR.
      We found that viscodissection using Healon provides outcomes comparable to
      conventional pick and scissors dissection. We also found that adjunctive use of
      silicone oil can salvage selected cases with particularly severe manifestations
      of PDR (e.g., the fibrinoid syndrome). With proper selection of patients and
      techniques, the anatomic success rate can exceed 80% even in the most severe
      cases. The goal of this paper is to show the applicability of using
      viscodissection and silicone oil infusion during vitrectomy in eyes with severe
      PDR.

PMID- 15513474
TI  - Combined pars plana vitrectomy and lens management in complex vitreoretinal
      disease.
AB  - Concurrent cataract and vitreoretinal disorders are relatively common.
      Additionally, a considerable number of phakic eyes develop visually significant
      cataract following pars plana vitrectomy. The ophthalmic literature is replete
      with reports of a combined procedure consisting of simultaneous cataract
      extraction, intraocular lens implantation, and pars plana vitrectomy to treat a
      wide range of vitreoretinal disorders and co-existing cataracts. Historical
      concerns of increased risk of complications with the combined procedure have been
      shown not to be clinically significant. The combined procedure offers the
      advantages of a single procedure, including faster recovery time and cost
      effectiveness. Earlier reports of the combined procedure describe pars plana
      lensectomy and extracapsular cataract extraction as techniques for cataract
      extraction. Currently, phacoemulsification with implantation of a foldable
      posterior intraocular lens implantation has become the preferred technique of
      cataract removal. With advances in instrumentation and surgical techniques, the
      combined procedure offers a safe and effective way to manage concurrent cataract
      and complex vitreoretinal disease.

PMID- 15513473
TI  - Visual outcomes of silicone oil versus gas tamponade for macular hole surgery.
AB  - PURPOSE: To determine the effectiveness of silicone oil versus gas tamponade to
      treat macular holes. METHODS: A retrospective review of patients who underwent
      macular hole repair with either silicone oil or gas tamponade. RESULTS: Data
      collected from 66 eyes from a retina only practice (Retina and Vitreous of Texas)
      were reviewed to assess visual outcomes of surgery with silicone oil versus 14%
      C3F8 gas tamponade. 21 eyes were non-randomized to silicone oil tamponade and 45
      eyes underwent gas tamponade. The average overall follow-up time was 11.8 months.
      Stage 2 holes constituted 9% of the holes; stage 3 and 4 made up 75%; recurrent
      holes were 11%; and 5% were traumatic holes. Of the macular holes not treated
      previously, 81.3% (13 of 16) were sealed successfully with silicone oil tamponade
      while 83.7% (36 of 43) of the gas-treated eyes were sealed. The overall primary
      closure rate was 83.1% (49 of 59). The pre-operative decimal visual acuity was
      0.104 (20/192) for the silicone oil group and 0.193 (20/104) for the gas-treated
      group. The post-operative decimal visual acuity at 1 year was 0.208 (20/96) for
      the silicone oil group and 0.453 (20/44) for the gas-treated group. The reopening
      rate for the silicone oil group was 14% (3 of 21) and 9% (4 of 45) for the gas
      treated group. The need for cataract surgery post macular hole repair was 36% (4
      of 11 phakic patients) for the silicone oil group and 61% (17 of 28 phakic
      patients) for the gas-treated group. CONCLUSIONS: With short-term follow-up
      silicone oil tamponade and gas tamponade are both successful in anatomic closure
      of macular holes. In eyes with macular holes surgically repaired with gas
      tamponade significant improvements in visual acuity are seen more frequently than
      eyes treated with silicone oil tamponade. Toxicity of silicone oil to the retinal
      pigment epithelium and/or photoreceptors may play a role in these results.

PMID- 15513475
TI  - Surgical treatments of central retinal vein occlusion.
AB  - Central retinal vein occlusion is a common retinal disease with usually severe
      complications. At present no safe treatment exists promoting the recovery of lost
      vision. Several surgical approaches to modify the natural course of the disease
      have been proposed in recent years. These options include laser-induced
      chorioretinal venous anastomosis, the injection of tissue plasminogen activator
      into a retinal vein, optic nerve decompression, and vitrectomy for macular edema.
      Even though all the proposed treatments have not yet been supported by randomized
      clinical trials, these techniques can be considered as innovative in an area
      where no effective treatment is available. Larger clinical trials are required to
      assess both the effectiveness and complication rate of surgical treatments
      designed to reverse the natural evolution of central retinal vein occlusion.

PMID- 15513476
TI  - Subthreshold and micropulse diode laser photocoagulation.
AB  - Retinal laser photocoagulation is a proven, effective treatment for various
      retinal disorders. Common clinical protocols use intra-operatively visible
      endpoints that cause iatrogenic chorioretinal damage. For this reason, laser
      therapy is normally limited to levels of disease severity for which the benefit
      to-risk ratio justifies its application. The use of 810 nm diode lasers in the
      MicroPulse mode offers the surgeon the possibility to minimize iatrogenic retinal
      damage. A less destructive laser therapy with a more favorable benefit-to-risk
      ratio could justify treatment earlier in the course of the disease, allowing for
      stabilization or improvement of less compromised visual functions.

PMID- 15513480
TI  - Image-guided surgical simulation--a proven improvement.

PMID- 15513477
TI  - Hyperhomocysteinemia in central retinal vein occlusion in young adults.
AB  - PURPOSE: Several investigators have tried to assess the role of
      hyperhomocysteinemia and the 677C-T mutation in the methylenetetrahydrofolate
      reductase (MTHFR) gene as risk factors in retinal vein occlusion with contrasting
      results. Aim of the study is to investigate the correlation between increased
      homocysteine plasma level and the homozygosity for the 677C-T mutation in the
      gene MTHFR in patients aged under 50 years affected by central retinal vein
      occlusion (CRVO). METHODS: Through a prospective, case-control study, 31 patients
      under 50 years of age and diagnosed with CRVO were compared with two control
      groups. The first control group (GROUP I) included 31 subjects matched for age,
      sex, laboratory tests and the main risk factors for atherosclerosis. The second
      control group (GROUP II) consisted of 31 volunteers matched only for age and sex.
      RESULTS: The mean homocysteine plasma level was 10.60 micromol/l in patients,
      10.39 micromol/l in GROUP I and 9.34 micromol/l in GROUP II. There was no
      statistically significant difference between mean homocysteine plasma level in
      cases and in GROUP I. Mean homocysteine plasma level was lower in GROUP II than
      in patients, and the difference was statistically significant. Homozygosity for
      the 677C-T mutation in the MTHFR was found in four patients (12.9%), in five
      controls in GROUP I (16.1%) and in four controls in GROUP II (12.9%). CONCLUSION:
      Our results support first of all the hypothesis that the homocysteine plasma
      level is not a primary and independent risk factor for central retinal vein
      occlusion, but is more likely a marker of atherosclerosis and the consequence of
      other well-established risk factors. Second, the importance of the design of the
      study is highlighted, since the obtained results differed on the basis of the
      considered control group. This feature could contribute to explain the
      contradictory results previously reported in the literature.

PMID- 15513481
TI  - Ligamentous reconstruction around the elbow using triceps tendon.
AB  - Posttraumatic instability of the elbow joint can be osseous or ligamentous.
      Ligamentous instability can be in valgus or in posterolateral rotatory direction.
      Rupture of both the lateral and medial collateral ligament of the elbow can be
      seen as an isolated injury, or it can be part of a more complex injury such as a
      dislocation. Persistent insufficiency of the lateral collateral ligament of the
      elbow results in posterolateral rotatory instability. Insufficiency of the medial
      collateral ligament, the anterior part in particular, results in valgus
      instability. Persistent symptoms after nonoperative treatment are an indication
      for reconstruction. In the past, ligamentous reconstruction at both the lateral
      and medial side was performed using palmaris tendon graft through bony drill
      holes. In this article I describe a new technique using ipsilateral triceps
      tendon, fixed in drill holes using bioabsorbable interference screws. This
      technique allows simplified graft tensioning and improved graft fixation, and
      avoids the risk of fracturing of the bony tunnels. An accelerated rehabilitation
      protocol can be applied. The final result depends on proper isometric
      reconstruction, associated lesions or degeneration of the elbow joint and
      adequate after-treatment. Taking these factors into account, the technique
      described shows promising short-term results.

PMID- 15513482
TI  - Operating time and survival of primary total hip replacements: an analysis of
      31,745 primary cemented and uncemented total hip replacements from local
      hospitals reported to the Norwegian Arthroplasty Register 1987-2001.
AB  - BACKGROUND: Some studies have found a significant decrease in operating time as a
      result of standardizing programs for hip surgery. To study the influence of
      operating time (skin to skin) on survival of total hip replacements, we
      investigated the operating time in local hospitals in Norway. We have found no
      other large published series of THRs investigating operating time and revision.
      PATIENTS AND METHODS: The study was based on 31,745 primary THRs reported to the
      Norwegian Arthroplasty Register from 47 local hospitals during 1987-2001.
      Operating time was divided into 7 categories, and for each category separate
      Kaplan-Meier curves and adjusted failure rate ratios were calculated. RESULTS:
      The mean operating time for all local hospitals in Norway was 96 (68-130) min.
      Increasing operating volume from less than 10 THRs/hospital/year to more than 200
      THRs/hospital/year was associated with a 25-min decrease in mean operating time
      in cemented THRs and a 35-min decrease in the case of uncemented THRs. With the
      operating time category of 71-90 min as reference category, cemented THRs that
      lasted more than 150 min had a two-fold increased (95% CI: 1.6-2.6) revision
      rate. For uncemented implants, the revision rate was 1.3 times higher (95% CI:
      0.8-2.2). Cemented implants with operating time under 51 min and over 90 min were
      associated with an increased risk of revision due to aseptic loosening. Cemented
      implants with operating time over 150 min were associated with an increased risk
      of revision due to infection. INTERPRETATION: Hospitals with long operating times
      should consider the potential benefit of reducing these times, as this may lead
      to lower revision rates and increased operating volumes. Shorter operation times
      could be achieved by standardization programs, but one should bear in mind that
      for cemented implants very short operating times also increased revision risk due
      to aseptic loosening.

PMID- 15513483
TI  - Hip revision using the Exeter stem, impacted morselized allograft bone and
      cement: a consecutive 5-year radiostereometric and radiographic study in 15 hips.
AB  - BACKGROUND: Impaction grafting in hip revision surgery is widely used but studies
      with mid- and long-term follow-up are scarce. PATIENTS, METHODS AND RESULTS: A 5
      year radiostereometric (RSA) follow-up of 15 hip revisions with the Exeter stem,
      morselized impacted allograft bone and cement revealed that 3 stems had not
      migrated between 2 and 5 years after revision, 11 stems had migrated to a minor
      degree in at least 1 direction, and 1 stem was loose according to RSA but without
      any radiographic signs of loosening or pain. The pain score was comparable to
      primary arthroplasties. INTERPRETATION: From a 5-year perspective, first-time hip
      revisions for aseptic loosening with impacted morselized allograft bone and
      cement appear to yield good clinical results, although stem migration continues
      to a minor degree 2 years after revision.

PMID- 15513484
TI  - Contamination of primary total hip replacements in standard and ultra-clean
      operating theaters detected by the polymerase chain reaction.
AB  - BACKGROUND: Many organisms that are responsible for low-grade infection after
      total hip replacement (THR) are not recognized by routine culture. PATIENTS AND
      METHODS: We examined wound contamination during primary total hip replacement
      performed in standard and ultra-clean operating theaters. 20 THRs were performed
      in each type of theater. Paired tissue specimens taken at the beginning and end
      of surgery were analyzed by bacterial culture and for the presence of bacterial
      DNA by the polymerase chain reaction (PCR). In total, 160 specimens (80 for
      culture, 80 for PCR) from 40 THRs were tested. RESULTS: In standard theaters,
      none of the 20 specimens taken at the start of surgery were positive by culture,
      but 3 were positive by PCR (15%). Of the 20 specimens taken at the end of
      surgery, 2 were positive by enriched culture and 9 were positive by PCR. All
      specimens positive by culture were also positive by PCR. In ultra-clean theaters,
      none of the 20 specimens taken at the start of surgery were positive by culture,
      but 2 were positive by PCR. Of the 20 specimens taken at the end of surgery, none
      were positive by culture, but 6 were positive by PCR. All specimens that were
      positive by culture were positive by PCR. INTERPRETATION: Wound contamination of
      primary THR occurs frequently in both standard and ultra-clean operating theaters
      and contamination is greater at the end of surgery than at the beginning
      (p=0.04). In this small series, we found no differences in wound contamination
      between standard and ultra-clean theaters (p=0.1).

PMID- 15513485
TI  - Neutrophils are active in total joint implant loosening.
AB  - BACKGROUND: Polymorphonuclear neutrophils (PMN) are the first cells to take part
      in the local foreign body reaction in aseptic loosening of endoprostheses. The
      aim of this study was to evaluate the systemic host reaction to total joint
      replacement by measuring the production of nitric oxide by neutrophils before and
      after total joint replacement. PATIENTS AND METHOD: Blood samples were collected
      from 33 patients (27 hips and 6 knees) before surgery, and 2 weeks, 2 months and
      2.5-3 years after surgery. The levels of nitric oxide produced by PMN were
      measured by the method described by Markert et al. (1994). RESULTS: Patients
      reporting pain in the region of the implant 3 years after surgery, and also
      patients with radiographic signs of loosening, had higher production of NO in the
      early period and 3 years after the implantation than those with good clinical
      results. INTERPRETATION: We propose that elevated levels of nitric oxide
      production by PMNs may serve as a marker of total joint prosthesis loosening.

PMID- 15513486
TI  - The cause of subchondral bone cysts in osteoarthrosis: a finite element analysis.
AB  - BACKGROUND: The etiology of subchondral bone cysts in arthrotic joints is
      unclear. MATERIALS AND METHODS: We used two-dimensional finite element analysis
      to evaluate the hypothesis that subchondral bone cysts in the osteoarthrotic hip
      joint may be the result of microfractures caused by localized cartilage defects
      or a thinned layer of cartilage. We evaluated the equivalent bone stress (von
      Mises (VM) stress) in the cancellous bone as an indicator of potential
      microfractures and further development of cystic lesions. RESULTS: Cartilage
      defects induced stress peaks in the subchondral bone. This peak stress
      distribution corresponded to the clinical observation of development of
      acetabular and femoral subchondral cysts in a "kissing" position. A femoral
      subchondral bone cyst induced a stress peak at the corresponding acetabular site,
      whereas subchondral acetabular cysts did not increase stress in the femoral head.
      Acetabular cysts showed an increased level of stress at the lateral and medial
      border of the lesion which was much higher than the stress levels in the femoral
      head, indicating a tendency to faster growth. INTERPRETATION: Our study supports
      the theory that stress-induced bone resorption may cause development of
      subchondral bone cysts in osteoarthrosis.

PMID- 15513487
TI  - Efficacy of vacuum bone cement mixing systems in reducing methylmethacrylate fume
      exposure: comparison of 7 different mixing devices and handmixing.
AB  - BACKGROUND: Polymethylmethacrylate (PMMA) bone cements are mainly used for
      implant fixation in joint replacement surgery. During cement preparation for
      application, all staff in the operating theatre are exposed to methylmethacrylate
      (MMA) fumes, which are known to have toxic side effects. METHODS AND RESULTS: In
      this study we found that vacuum mixing of bone cement with 7 commercially
      available mixing devices significantly reduced the emission of MMA vapors in the
      breathing zone when compared with classic hand mixing in an open bowl. Gas
      chromatography appears to be more sensitive for detection of MMA fumes than Photo
      Inonization Detection. INTERPRETATION: According to present knowledge, even
      repeated mixing of PMMA bone cement during a normal working day does not seem to
      constitute an increased health risk, particularly if vacuum mixing is
      implemented.

PMID- 15513488
TI  - Do we really need to routinely crossmatch blood before primary total knee or hip
      arthroplasty?
AB  - BACKGROUND: A maximum surgical blood ordering schedule may lead to wastage of
      valuable resources due to over-ordering of blood and/or under-utilisation. We
      audited the results of a group-and-save (GS) policy for primary hip (THR) and
      knee (TKR) arthroplasty to evaluate its safety and practicality. PATIENTS AND
      METHODS: We conducted a retrospective review of consecutive patients attending
      for THR (177) or TKR (137) over a period of 8 months (phase 1). Following
      introduction of a limited GS policy, 205 THR and 147 TKR were reviewed
      prospectively over a corresponding period of 8 months (phase 2). Corresponding
      THR and TKR groups in each phase were comparable with respect to age, gender,
      length of stay, operating surgeon, pre- and lowest postoperative hemoglobin,
      reason for and timing of transfusion. Quantities (units) of blood requested pre-
      and postoperatively, transfused and returned to the blood bank, were recorded.
      RESULTS: 77 and 62% of all blood requested for THR and TKR, respectively, in
      phase 1 was not used. 58 and 21% of patients undergoing THR and TKR,
      respectively, in phase 2 underwent preoperative GS, with 92% and 100% of all
      blood requested being used for transfusion. Overall, the quantity of blood
      returned was reduced by 25% for the THR group. Transfusion rates fell by 9% and
      5% for the TKR and THR groups, respectively. We found no adverse events
      associated with blood from a GS sample. Cost savings of 37 800 euro were
      calculated estimated for the study period (phase 2). INTERPRETATION: For routine
      primary THR/TKR, GS policy is a safe procedure. Reduction in non-utilisation of
      blood has economic and cost-saving implications for limited healthcare resources.
      Having subsequently introduced a group-and-save policy for all patients
      undergoing routine THR/TKR, considerable savings have been identified after only
      2 months.

PMID- 15513489
TI  - Robotic total knee arthroplasty: the accuracy of CT-based component placement.
AB  - BACKGROUND: Accurate alignment of the components in total knee arthroplasty is
      important. By use of postoperative CT controls, we studied the ability of a
      robotic effector to accurately place and align total knee arthroplasty (TKA)
      components according to a purely CT-based preoperative plan. PATIENTS AND
      METHODS: Robotic TKA was performed in 13 patients (6 men) with primary
      gonarthrosis. Locator screws were placed into femur and tibia under spinal
      anesthesia. A CT-scan including the femoral head, knee and ankle was performed.
      In the preoperative planning software, virtual components were positioned into
      the CT volume. In a second operation, the robot milled femur and tibia with a
      high-speed milling tool according to the preoperative plan. On the 10th day, CT
      controls were performed following the same protocol as preoperatively. RESULTS:
      The mean deviation of the postoperative from the preoperatively planned
      mechanical axis was 0.2 degrees (95% CI: -0.1 degrees to 0.5 degrees ). The
      accuracy of angular component placement in frontal, sagittal and transverse
      planes was within +/-1.2 degrees , and the accuracy of linear component placement
      in mediolateral, dorsoventral and caudocranial directions was within +/-1.1 mm.
      INTERPRETATION: Robotic TKA allows placement of components with unparalleled
      accuracy, but further development is mandatory to integrate soft-tissue balancing
      into the procedure and make it faster, easier and cheaper.

PMID- 15513490
TI  - Pain in arthroscopic knee surgery under local anesthesia.
AB  - BACKGROUND: We evaluated pain during arthroscopic knee surgery performed under
      local anesthesia, with respect to various types of lesions and specific
      procedures used. PATIENTS AND METHODS: Arthroscopic surgery was performed on 63
      joints (61 patients), with a median age of 49 years. We asked the patients to
      describe the pain experienced at each step of the procedure, and to compare the
      level of pain experienced at the time of injection and during the operation,
      using a visual analog scale (VAS). RESULTS: Pain experienced at the time of
      injection of the local anesthetic was more severe than the pain experienced
      during the surgical procedure. Local anesthesia provided good pain control during
      partial resection of the meniscus, chondroplasty, and removal of free bodies.
      Patients sometimes experienced more pain during treatment of the suprapatellar
      pouch, including the plica and the anterior cruciate ligament. INTERPRETATION:
      Injection of the local anesthetic was usually the most painful phase of the
      entire procedure. Patients were generally satisfied with the pain control.

PMID- 15513491
TI  - A miniature and mobile intermittent pneumatic compression device for the
      prevention of deep-vein thrombosis after joint replacement.
AB  - The WizAir-DVT is a miniature, lightweight (690 g), battery-operated and mobile
      intermittent pneumatic compression device (ICD), which enables continuous
      intraoperative use and immediate patient mobilization postoperatively. We
      compared its efficacy with a commonly used ICD, the Kendall SCD. Peak femoral
      vein flow velocity was measured in 20 apparently healthy volunteers at rest and
      with each device: we found no significant differences between them. A second
      prospective, randomized, clinical trial was used to compare the efficiency of the
      device in preventing deep venous thrombosis (DVT) after joint replacement in 50
      patients (n=25/group). None developed DVT. Doppler ultrasonography revealed no
      significant differences. The WizAir-DVT antithrombotic compression device is as
      safe and effective as the Kendall SCD.

PMID- 15513492
TI  - Greater frequency of distraction accelerates bone formation in open-wedge
      proximal tibial osteotomy with hemicallotasis.
AB  - BACKGROUND: In chickens, increased distraction frequency stimulates bone
      formation in distraction osteogenesis. PATIENTS AND METHODS: We investigated the
      effect of two different distraction frequencies on bone formation in the
      distracted portion, and on the time of removal of the fixator, in open-wedge
      osteotomies of the proximal tibia with hemicallotasis (HCO). The study included
      20 consecutive patients (20 knees) who underwent HCO for medial osteoarthrosis of
      the knee. 10 knees were distracted at a rate of 0.25 mm four times a day (the 4
      step group); and the other 10 knees were distracted at a rate of 0.125 mm eight
      times a day (the 8-step group). RESULTS: There were no significant differences in
      the preoperative FTAs or the correction angles between the two groups. At all
      intervals until 6 weeks after the completion of distraction, bone mineral density
      in the distraction gap was significantly higher in the 8-step group than in the 4
      step group. The average time in external fixation was 78 (SD 5) days in the 8
      step group as compared to 89 (SD 6) days in the 4-step group, a significantly
      shorter time. INTERPRETATION: Our findings indicate that an increase in the
      distraction frequency in HCO provides better bone formation, resulting in a
      shorter external fixation period.

PMID- 15513493
TI  - Positive pivot shift after ACL reconstruction predicts later osteoarthrosis: 63
      patients followed 5-9 years after surgery.
AB  - BACKGROUND: Rupture of the anterior cruciate ligament (ACL) may cause
      osteoarthrosis (OA) and functional impairment. We wanted to find out whether the
      degree of knee stability obtained after ACL reconstruction correlates with
      radiographic and clinical outcome. PATIENTS AND METHODS: We examined 63 patients
      2 and 5-9 years after anterior cruciate ligament (ACL) reconstruction. Knee
      stability was assessed 2 years after surgery by recording AP laxity using
      radiostereometric technique (RSA) and by performing the pivot shift test.
      Degeneration of the knee joint was evaluated with bone scintigraphy, and
      radiographically. Functional outcome was assessed with Lysholm score, Tegner
      activity scale and with the one-leg hop test. RESULTS: Radiographic signs of
      osteoarthrosis at the most recent follow-up (5-9 years) did not correlate with
      knee stability. Patients with positive pivot shift test 2 years after surgery
      showed increased scintigraphic activity of the subchondral bone at the most
      recent follow-up, and inferior subjective functional outcome 2 years after
      surgery. Knees having had meniscus resections had more often OA. Radiographical
      signs of OA were associated with higher scintigraphic uptake in the operated knee
      relative to the contralateral knee. INTERPRETATION: The ability to obliterate the
      pivoting by ACL reconstruction appears to be more important than normalizing the
      AP laxity in order to prevent later OA.

PMID- 15513494
TI  - Periprosthetic tibial bone mineral density changes after total knee arthroplasty:
      one-year follow-up study of 69 patients.
AB  - BACKGROUND: The critical structure supporting the prosthetic components in total
      knee arthroplasty (TKA) is tibial trabecular bone. The quality of tibial bone can
      be evaluated by bone mineral density (BMD) measurements. PATIENTS AND METHODS: We
      prospectively measured changes in BMD in the proximal tibia after cemented TKA in
      osteoarthrotic knees. 69 patients were scanned by dual-energy X-ray
      absorptiometry (DXA) within a week after surgery, and after 3, 6 and 12 months.
      RESULTS: At baseline, the medial region of interest (ROI) BMD was higher in the
      varus knees than in the valgus aligned knees (p=0.02). The medial metaphyseal ROI
      showed a decrease in BMD during the follow-up in preoperatively varus knee joints
      (p<0.001). In preoperatively valgus knees, there was a slight increase in medial
      compartment BMD which was not significant (p=0.2). Alignment correction in both
      groups showed bone remodeling giving similar medial and lateral BMD values,
      suggesting that the bone became equally strong in both compartments of the
      metaphysis. There was no association between increasing American Knee Society
      (AKS) scores and bone remodeling. INTERPRETATION: We suggest that this remodeling
      is caused by postoperative changes in tibial loading. Our results support the
      clinical importance of recreating proper valgus alignment of the knee joint in
      the TKA operation, thus possibly providing better conditions for longevity of the
      tibial component.

PMID- 15513495
TI  - Increased flexion and reduced hospital stay with continuous intraarticular
      morphine and ropivacaine after primary total knee replacement: open intervention
      study of efficacy and safety in 154 patients.
AB  - BACKGROUND: A single injection of bupivacaine after wound closure reduces the
      need for analgesics and increases flexion after total knee replacement (TKR). We
      have therefore studied the effect of continuous injection of morphine and
      ropivacaine after TKR on range of movement and length of hospital stay. PATIENTS
      AND METHODS: In an open intervention study, we assigned 154 consecutive patients
      who had primary unilateral TKR for osteoarthrosis. The intervention was
      continuous intraarticular injection of morphine 20 mg/mL, 0.5 mL plus ropivacaine
      2 mg/mL, 100 mL; bolus 20 mL and 2 mL/hour from 24 to 72 hours postoperatively.
      Group 1 (10 women and 8 men) received standard postoperative analgesics and group
      2 (11 women and 7 men) also received continuous intraarticular morphine and
      ropivacaine as described above. Group 3 (14 women and 4 men) received double this
      dose (4 mL/hour) from 24 to 72 hours postoperatively. To assess the safety of the
      intraarticular treatment, an additional group of 100 consecutive patients was
      followed (group 4). RESULTS: At discharge, flexion was 70 degrees (60-100) in
      group 1, 100 degrees (70-115) in group 2 and 110 degrees (90-130) in group 3.
      Hospital stay was reduced from 9 (7-11) days in group 1, to 7 (5-10) days in
      groups 2 and 3. Number of days elapsed until the patient was walking with
      crutches was reduced from 5 (3-8) to 4 (3-6) and 3 (3-9), respectively. In the
      intervention groups, the need for analgesics was reduced during the hospital
      stay. Deep infection was registered in 1 patient. INTERPRETATION: Continuous
      intraarticular morphine and ropivacaine reduce pain and enhance rehabilitation
      after total knee replacement. Before advocating this as a standard procedure,
      further large-scale randomized studies will be needed to assess the safety of
      this regimen.

PMID- 15513496
TI  - Laser-induced thermal stress and the heat shock response in neural cells.
AB  - BACKGROUND: The Ho: YAG laser is used extensively in orthopedic surgery. It
      offers a minimally invasive method of ablating tissue with precision. Previous
      studies have explored the effects of laser use on temperature during experimental
      foraminoplasty. To date, there has been limited work on the effects of thermal
      stress on cells in this context. Material and methods Cells were exposed either
      to heated medium or the Ho: YAG laser in the high-power mode. Heated medium was
      used as a stressor by (I) exposing groups of cells to a constant temperature of
      45 degrees C for varying lengths of time: 5, 10, 15 and 20 min, and (II) exposing
      cells for a fixed length of time (5 min) to varying temperatures: 45 degrees C,
      55 degrees C, 65 degrees C with a control treated at 37 degrees C. A third group
      was subjected to direct laser treatment. The effects of the treatments were
      assessed using trypan blue staining as a measure of viability and
      immunocytochemistry was used to measure changes in heat shock protein (HSP)
      expression. RESULTS: There was a negative correlation between cell viability and
      HSP expression, and between cell viability and the severity of the treatment.
      INTERPRETATION: Our findings suggest a possible role for the Ho: YAG laser in
      spinal foraminoplasty based on the high level of cell viability in the treatment
      regimen that most closely mirrored the clinical application of the laser.

PMID- 15513497
TI  - Bone grafting the scaphoid nonunion: a systematic review of 147 publications
      including 5,246 cases of scaphoid nonunion.
AB  - In order to elucidate the history of scaphoid nonunion and to evaluate whether or
      not the problem has been solved, we have reviewed the literature from 1928 to
      2003 for union rates, postoperative immobilization periods and complications of
      the different scaphoid bone grafting procedures. The outcomes of 5 246 scaphoid
      nonunions were evaluated in three treatment groups. In the first group involving
      nonvascularized bone grafting without internal fixation, we found a union rate of
      80% (95% CI: 78-82) after an average immobilization period of 15 weeks. In the
      second group involving nonvascularized bone grafting with internal fixation, the
      figures were 84% (CI: 82-85) and 7 weeks, respectively. In the last group
      involving vascularized bone grafting with or without internal fixation, the
      figures were 91% (CI: 87-94) and 10 weeks, respectively. We found no prospective
      randomized studies comparing different operative treatments of scaphoid nonunion.
      We conclude that there still is a need for improvement in the treatment of
      scaphoid nonunion.

PMID- 15513498
TI  - Selective botulinum toxin injection in the treatment of recurrent deformity
      following surgical correction of club foot: a preliminary report of 3 children.
AB  - Management of a child with club foot deformity that recurs after an apparently
      successful posteromedial soft tissue release remains a challenge. Revision
      surgery is often attempted, but this carries a high risk of significant scarring
      or neurovascular complications. We have treated 3 children (3 feet) with relapsed
      club foot and fixed deformities, using Botulinum toxin A (BTX-A) injection into
      muscle groups clinically thought to be responsible for recurrent deformity,
      followed by moulded plaster casts. Two cases have maintained a good foot position
      with an minimum follow-up of 18 months, and one other is also doing well having
      had a tibialis anterior tendon transfer as well as the BTX-A therapy. In our
      limited experience, targeted BTX-A injection with plaster casting has been safe,
      and may obviate the need for major revision surgery in a proportion of cases with
      recurrent club foot deformity following previous posteromedial soft tissue
      release.

PMID- 15513499
TI  - Revision shoulder arthroplasty with morselized bone allograft--a case report.

PMID- 15513503
TI  - Nitric oxide induces apoptosis of the hair cells of cochlea.
AB  - OBJECTIVE: Nitric oxide (NO) has a toxic effect on neuronal cells related to
      glutamate receptors. NO released from post-synaptic cells with glutamate
      receptors can induce nearby cell death. In this experiment, we examined the
      effect of NO on cochlear hair cells. METHODS: Two concentrations, 0.5 and 0.1
      molar concentration (MC) of 1-hydroxy-2-oxo-3-(3-aminopropyl)-3-isopropyl-1
      triazene (NOC-5), which is a NO donor, were placed on the round window of the
      guinea pig cochlea and its morphological changes were investigated at 12, 28, 72
      h after the treatment. RESULTS: By the trypan blue dye extrusion method, the cell
      death was recognized in the outer hair cells at the percentage 0, 36.0+/-6.6,
      4.9+/-1.2% at 12, 28, 72 h after treatment respectively in the group 0.5 MC NOC
      5, but no inner hair cell death was recognized. In the group of 0.1 MC NOC-5 and
      control any cell death was not detected. Transmission electron microscopy
      revealed this cell death was characteristic of apoptosis. CONCLUSION: The
      findings that apoptosis was induced in the outer hair cells of the organ of Corti
      by NO suggests the possibility that the cochlea is affected when extra NO release
      occurs there, leading to cochlear dysfunction.

PMID- 15513504
TI  - Probable function of Boettcher cells based on results of morphological study:
      localization of nitric oxide synthase.
AB  - Boettcher cells lie on the basilar membrane beneath Claudius cells. The cells are
      considered supporting cells for the organ of Corti, and present only in the lower
      turn of the cochlea, which responds to high-frequency sound. Boettcher cells
      interdigitate with each other, and project microvilli into the intercellular
      space. Their structural specialization suggests that Boettcher cells may play a
      significant role in the function of the cochlea. Nitric oxide synthase (NOS) has
      previously been detected in substructures of the cochlea. In the cochlea, it is
      believed that nitric oxide plays an important role in neurotransmission, blood
      flow regulation, and induction of cytotoxicity under pathological conditions.
      Findings concerning detection of NOS on Boettcher cells are rare. We demonstrated
      here the localization of NOS on Boettcher cells of the rat by
      immunohistochemistry using polyclonal antibody to NOS. On observation with the
      light microscope using DAB staining, positive immunostaining to NOS was observed
      in Boettcher cells. In immunoelectron micrographs, NOS was detected abundantly in
      the cytoplasm of the interdigitations. This suggests that the interdigitations
      may play significant roles by using NOS. It follows from this that the nitric
      oxide (NO) on Boettcher cells may influences neighboring Boettcher cells. The
      ultrastructure of Boettcher cells suggests that they may be active cells, which
      perform both secretory and absorptive functions.

PMID- 15513505
TI  - Further examination of infants referred from newborn hearing screening.
AB  - OBJECTIVES: Universal newborn hearing screening (UNHS) is considered beneficial
      and is accepted worldwide. However, some problems remain, and administrative
      systematization has yet to be established in many countries. This study assessed
      the hearing screening of referred newborn infants and discusses the problems that
      remain. MATERIALS AND METHODS: Over the two years from July 2001 to June 2003, 98
      ears of 49 infants were judged as a "referral" from a newborn hearing screening
      program, and were subsequently referred to our hospital for further examination
      using conventional ABR and other audiological tests. The methodology used for
      hearing screening varied between practitioners and hospitals that utilized both
      different recording apparatus for AABR and/or automated DPOAEs and independent
      protocols. RESULTS: Conventional ABR identified 21 infants with bilateral normal
      hearing, 12 with unilateral hearing loss, and 16 with bilateral hearing loss, and
      a total correspondence rate of 40.8% (20 out of 49 infants). In a comparative
      analysis, 26 ears out of 98 (26.5%) were determined as false-positive, seven out
      of 98 as false-negative (7.1%), and there was a total correspondence rate of
      66.3% (65 out of 98 ears). Five of the seven false-negative cases who were
      referred with unilateral hearing loss exhibited moderate to profound bilateral
      hearing loss (moderate; one infant, severe to profound; four infants). Of the 16
      infants with bilateral hearing loss, nine with more than moderate loss had
      hearing aids fitted at our hospital or related educational institution before
      most were six months old. CONCLUSIONS: Our results suggest the accuracy of
      newborn hearing screening remains an issue, but may be improved by an experienced
      examiner and better protocols including a two-stage process and altered timing of
      screening. Other ongoing health care programs need to monitor for signs of
      hearing loss even in the "passed" infants because of possible false-negatives and
      delayed-onset hearing loss. Improvement is needed in both the intervention
      systems and diagnostic follow-up of hospitals. Early public support is also
      required for infants with either severe to profound or moderate hearing loss.
      From the viewpoint of test conditions and puerperal parental psychological
      problems, it is considered that the timing of screening needs further discussion.
      Here it is suggested that screening should be performed within the first three
      months of infant's life but not be limited to before hospital discharge, and
      incorporated into the routine health care program for one-month-old infants
      without reducing efficiency.

PMID- 15513506
TI  - Changes in input/output function of distortion product otoacoustic emissions
      during the glycerol test in Meniere's disease.
AB  - OBJECTIVE: To investigate the manner of change in the input/output (I/O) function
      of distortion product otoacoustic emissions (DPOAEs) during the glycerol test in
      patients with Meniere's disease. MATERIAL AND METHODS: The DPOAE I/O functions at
      three F2 frequencies of 1001, 1501, and 2002 Hz were measured before and after
      the glycerol test following pure-tone audiometry for 16 ears of 16 patients with
      unilateral Meniere's disease. Changes in DPOAE I/O function during the glycerol
      test were analyzed using maximum level of DPOAEs (max. DP level) and the
      detection threshold of DPOAEs (DP threshold) in the I/O function as parameters.
      RESULTS: Significant changes in I/O function during the glycerol test were
      observed for at least one of three F2 frequencies in all 8 ears and 6 of 8 ears
      with and without positive test results, respectively, regardless of change in
      pure-tone thresholds at 1000 and 2000 Hz. A total of 12 ears exhibited two
      findings of significant change in parameters indicating improvement of cochlear
      function, increase in max. DP level and lowering of DP threshold, and 2 ears
      exhibited decrease in max. DP level, a finding indicative of deterioration of
      cochlear function. Neither of the two parameters exhibited significant change
      simultaneously, except in one I/O function. Moreover, there appeared to be no
      clear relationship between the parameter exhibiting significant change and F2
      frequencies or changes in pure-tone threshold. CONCLUSION: Subtle changes in
      cochlear function during the glycerol test can be detected with higher
      sensitivity by measurement of the DPOAE I/O function than by conventional
      audiometry. However, multiple parameters should be used in analysis of change in
      the I/O function since it is difficult to predict how the I/O function will
      change prior to the glycerol test. Furthermore, the high sensitivity of DPOAEs in
      detecting change in cochlear function may provide useful information on inner ear
      status in Meniere's disease.

PMID- 15513507
TI  - Temporal resolution and speech recognition ability of patients with retrocochlear
      auditory dysfunction.
AB  - OBJECTIVE: To study the effect of temporal resolution measured by gap detection
      tasks on the speech recognition ability of patients with retrocochlear auditory
      dysfunction. MATERIAL AND METHODS: The gap detection thresholds (GDTs) for
      dichotic stimuli were measured for 23 patients with retrocochlear auditory
      dysfunction confirmed by abnormal auditory brainstem responses the relationship
      between GDTs and maximum speech recognition scores (max. SRSs) in quiet was
      examined. In gap detection testing, narrow-band noises of the five center
      frequencies of 0.25, 0.5, 1.0, 2.0, 4.0 kHz were used as leading and trailing
      markers. Each of these two marker sounds was presented to the opposite ear at 20
      dBSL with various gap durations between them. RESULTS: Abnormal GDTs were
      observed at one or more test frequencies in 17 of 23 patients. In 12 patients,
      abnormal GDTs were found at four or five test frequencies. These 12 patients
      included 4 patients with poor max. SRS less than 30%. However, no tendency was
      found for max. SRSs to be poorer as abnormal GDTs were observed for more test
      frequencies. CONCLUSION: Temporal resolution measured by gap detection for
      dichotic stimuli was frequently reduced in patients with retrocochlear auditory
      dysfunction, and this reduction appeared to spread over a wide frequency range
      when speech recognition had markedly deteriorated. However, it also appeared that
      reduced temporal resolution for dichotic stimuli might not necessarily imply poor
      speech recognition in quiet.

PMID- 15513508
TI  - Positional and positioning nystagmus in healthy subjects under
      videonystagmoscopy.
AB  - OBJECTIVE: The eye-focused video camera as sensitive to infrared light is very
      useful for detecting nystagmus with open eyes in the dark. The existence of
      physiological nystagmus has been reported. We investigated how frequently
      physiological positional and positioning nystagmus is seen in healthy individuals
      under infrared video goggles. MATERIALS AND METHODS: Eighty-nine healthy
      individuals were examined in this study. Positional and positioning nystagmus was
      examined with infrared video goggles. RESULTS: Positional nystagmus could be
      detected in 65 of the 89 subjects under infrared video goggles. The majority of
      nystagmus was horizontal nystagmus, and vertical nystagmus was also seen in four
      subjects. Nystagmus was most frequently recognized in right or left shoulder down
      position. Positioning nystagmus was detected in 40 subjects. CONCLUSIONS:
      Positional and positioning nystagmus frequently exist in healthy subjects. This
      finding means that the existence of physiological nystagmus must be considered
      when diagnosing dizzy patients using this equipment.

PMID- 15513509
TI  - Application of modified transmastoid approach methods to congenital atresia of
      the external ear canal with middle ear infection.
AB  - OBJECTIVE: To present our surgical technique for congenital atresia of the
      external ear canal with middle ear infection. METHODS: A modified transmastoid
      approach to congenital atresia of the external ear canal with middle ear
      infection was applied. Our method is to visualize the landmarks of the mastoid
      cavity such as the antrum, sinodural angle and digastric ridge by the canal-open
      method to avoid facial nerve injury and then prepare a relatively large external
      ear canal with reconstruction of the posterior wall of the external ear canal.
      RESULTS AND CONCLUSION: This method is suitable not only for treating congenital
      atresia of the external ear canal with middle ear infection, but also for
      avoiding facial nerve injury and postoperative complications such as re-stenosis
      of the new ear canal and postoperative middle ear infection.

PMID- 15513510
TI  - Fibrous dysplasia of the temporal bone with cholesteatoma.
AB  - Fibrous dysplasia is an uncommon benign bone disorder of unknown origin. It
      rarely affects the temporal bone. We report a case of fibrous dysplasia of the
      temporal bone with cholesteatoma in the external auditory canal, the first
      complaint of which was left otorrhea. Fibrous dysplasia invaded the external ear
      canal, stenosis of which causes a cholesteatoma. Mastoidectomy, tympanoplasty,
      and meatoplasty were performed. We discuss the characteristics of this condition,
      its differential diagnosis and its treatment.

PMID- 15513511
TI  - A pedigree with Pendred syndrome: case report and discussion on hereditary
      hearing loss.
AB  - After presenting the case of a Japanese pedigree with Pendred syndrome we discuss
      whether congenital hearing loss such as Pendred syndrome can be avoided.

PMID- 15513512
TI  - Magnetic resonance imaging for diagnosis of congenital anosmia.
AB  - Magnetic Resonance Imaging (MRI) was performed on 9 patients who lacked a sense
      of smell since birth. Seven of them, including two patients with Kallmann
      syndrome, exhibited abnormality of the olfactory bulb, olfactory tract, olfactory
      sulcus, or rectus gyrus, with some variation among patients in type and degree of
      abnormality. The other two patients exhibited normal olfactory pathway
      morphology, and for them the possibility of acquired sensorineural anosmia could
      not be ruled out. MRI is useful for determining whether patients with congenital
      anosmia have olfactory pathway anomalies. Many patients with congenital anosmia
      and hypoplasty or aplasty of the olfactory pathway nevertheless had no gonadal or
      endocrinological disorders.

PMID- 15513513
TI  - Concurrent chemoradiotherapy with pirarubicin and 5-fluorouracil for resectable
      oral and maxillary carcinoma.
AB  - OBJECTIVE: We present the response rate and adverse effects of our regimen of
      concurrent chemoradiotherapy with pirarubicin (THP) and 5-fluorouracil (5-FU) for
      oral and maxillary carcinoma. PATIENTS AND METHODS: Fifteen patients with oral
      (10 cases) or maxillary (5 cases) squamous cell carcinoma who underwent our
      concurrent chemoradiotherapy with the combination of intraarterial pirarubicin,
      intravenous continuous 5-fluorouracil, and radiation between March 2001 and
      February 2003 in our department were entered in this study. THP (5 mg/day) was
      infused into the lingual or maxillary artery one hour before radiation on days 1
      5 and 8-12, while intravenous 5-FU (150 mg/m2/day) was instilled continuously on
      days 1-5, 8-12, 15-19, and 22-26 in accordance with the radiation schedule (2
      Gy/day). Consequently, total doses of THP, 5-FU, and radiation were 50 mg, 3000
      mg/m2 and 40 Gy, respectively. After the treatment series, response rate and
      adverse effects were evaluated. RESULTS: Response rate achieved 100% (12 cases
      exhibited a complete response and the remaining 3 a partial response). Notably,
      all 10 patients with oral carcinoma exhibited complete response. The main adverse
      effects were leucopenia (6/15) and mucositis (6/15), both of which were
      acceptable. CONCLUSIONS: This concurrent chemoradiotherapy is very useful for
      oral and maxillary carcinoma as a preoperative modality with remarkably high
      response rate and acceptable adverse events.

PMID- 15513514
TI  - Accelerated hyperfractionated irradiation with concomitant boost for stage II
      laryngeal cancer and locally advanced head and neck cancer.
AB  - OBJECTIVE: This study was conducted to evaluate the efficacy and feasibility of
      our accelerated hyperfractionation with concomitant boost for stage II laryngeal
      cancer and stages III-IVb locally advanced head and neck cancer. PATIENTS AND
      METHODS: From January 2000 to October 2001, eight patients with AJCC 1998 stage
      II laryngeal cancer and 11 patients with AJCC 1998 stages III-IVb locally
      advanced head and neck cancer underwent accelerated hyperfractionated radiation
      therapy. For the stage II laryngeal cancer, radiation was delivered at a 2.0 Gy
      fraction a day, 5 fractions per week for the first 3 weeks, then 2 fractions (1.8
      and 1.2 Gy) a day, 5 times a week for 2.5 weeks, with total dose of 69 Gy. For
      stages III-IVb head and neck cancer, radiation was given at a 1.8 Gy fraction a
      day, 5 fractions per week for 6 weeks and a boost was added up to 70.5 Gy with
      1.5 Gy as a second daily fraction during the last 2.2 weeks. Among the patients,
      16 (84%) received concomitant chemotherapy, mainly with low-dose carboplatin.
      Acute toxicity based on RTOG criteria and tumor response at 1 month post
      treatment were estimated as initial effects. RESULTS: The overall response rate
      was 100% in patients with stage II laryngeal cancer and 91% in patients with
      stages III and IVb head and neck cancer. The incidence of grade 3 or worse acute
      effects was 47%. Eighteen patients (95%) completed radiation therapy without
      interruption related to acute side effects, while one had prolongation of the
      treatment for more than 1 week because of neutropenia. CONCLUSIONS: Our results
      demonstrated that accelerated hyperfractionation, mostly combined with
      concomitant chemotherapy, had a good overall response rate with acceptable
      toxicity in stage II laryngeal cancers and stages III-IVb head and neck tumors.

PMID- 15513515
TI  - A possible case of Werner syndrome presenting with multiple cancers.
AB  - The treatment of a man with six metachronous primary cancers is described. The
      primary lesions were in the soft palate, both edges of the tongue, the hard
      palate, the esophagus, and the right ureter. Pathologically, all of the first
      five tumors in the head and neck and esophagus were proven to be squamous cell
      carcinoma with various grades of differentiation, and the last one was
      transitional cell carcinoma. The cancers were found in the early clinical stage,
      and were completely controlled one by one except for the ureteral tumor under
      treatment. His characteristic medical history and physical findings, i.e.
      bilateral cataracts, short stature, baldness, diabetes mellitus, high-pitched
      voice, and multiple malignancies, met the clinical criteria for possible Werner
      syndrome, a genetic premature aging disorder, though the possibility of phenocopy
      of this syndrome has not been ruled out. We have followed him carefully because
      he might be vulnerable to malignant tumor formation.

PMID- 15513516
TI  - A case of fatal respiratory failure after surgery for advanced supraglottic
      laryngeal carcinoma.
AB  - Pulmonary lymphangitic carcinomatosis (PLC) is an uncommon type of pulmonary
      metastasis from laryngeal carcinoma. We encountered a case of fatal respiratory
      failure after surgery for supraglottic laryngeal carcinoma with multiple cervical
      lymph node metastases. On day 25 postoperatively, the patient suddenly developed
      fever and noted slowly progressive difficulty in breathing. Laboratory data,
      radiological findings, and the clinical course of this patient were strongly
      suggestive of PLC. The patient refused fiberoptic bronchoscopy and glucocorticoid
      therapy, leading to rapid deterioration due to increasing respiratory distress,
      and died of respiratory failure on postoperative day 32. PLC should be considered
      a possible presentation of pulmonary metastasis associated with head and neck
      carcinoma. Chest CT may be needed to detect subclinical PLC, especially in cases
      of advanced head and neck carcinomas.

PMID- 15513517
TI  - The syndrome of inappropriate antidiuretic hormone secretion associated with
      chemotherapy for hypopharyngeal cancer.
AB  - The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is
      characterized by hyponatremia and the plasma hypoosmolality induced by water
      retention attributable to persistent antidiuretic hormone (ADH) release. It has
      been reported that SIADH may occur due to various factors in patients with
      malignant tumor. We report a case of hypopharyngeal cancer complicated by SIADH
      following chemotherapy. A 72-year-old woman with hypopharyngeal cancer was
      treated by oral administration of S-1 and intravenous administration of low-dose
      cisplatin following radiation therapy. General fatigue and coma occurred during
      the third course of this chemotherapy, using S-1 and low-dose cisplatin. We
      believed that she had SIADH because of the results of examinations including
      hyponatremia, serum hypoosmolality and increasing serum ADH level. We treated her
      by fluid restriction and intravenous administration of hypertonic saline and
      furosemide, and she recovered. Unfortunately, her hypopharyngeal cancer gradually
      progressed and she died of acute pneumonia three months later.

PMID- 15513518
TI  - A case of simultaneous primary carcinomas of the tongue.
AB  - Reports of multiple primary cancers are increasing, but simultaneous primary
      cancers are not frequently reported especially originated in the same organ. We
      encountered a 71-year-old female who had two simultaneous carcinomas at both
      edges of the tongue. Histologically, the carcinoma of the right edge was a well
      differentiated squamous cell carcinoma, while that on the left edge was a
      moderately-differentiated squamous cell carcinoma. No other tumors were detected
      on other examinations, including gallium-67 scintigraphy, CT scan of the chest,
      upper gastrointestinal fiberscopy and so on. She underwent surgical treatment
      without other induction treatments such as radiotherapy and chemotherapy. Her
      postoperative radiotherapy and chemotherapy were also uneventful because of her
      age. Fourteen-month follow-up revealed neither recurrence nor metastasis.

PMID- 15513519
TI  - A case of cervical paraganglioma: usefulness of FDG PET imaging and a possibility
      of rare origination.
AB  - Cervical paragangliomas are rare tumors derived from neural crest cells. Anatomic
      imaging techniques rely upon the characteristic spatial relations and the high
      vascularity of this tumor. Results of computed tomography (CT), magnetic
      resonance imaging (MRI), and arteriography initially led us to the preoperative
      diagnosis of cervical paraganglioma. In our case, 2-[18F]-fluoro-2-deoxy-D
      glucose positron emission tomography (FDG PET), a type of functional imaging, was
      also carried out and demonstrated abnormally increased tracer uptake; this
      approach was thus successful for visualizing paraganglioma. FDG PET imaging may
      be useful in the detection of benign paraganglioma. On surgical exploration of
      the neck, the tumor was found to arise from the vagus nerve, whereas the
      hypoglossal nerve was encompassed by the tumor in its upper portion. The
      intraoperative findings suggested the possibility that the tumor had arisen from
      the hypoglossal nerve.

PMID- 15513521
TI  - Extranasopharyngeal angiofibroma: etiology, incidence and management.
AB  - OBJECTIVE: Angiofibromas in the head and neck area usually arise in the
      nasopharynx (NA) in adolescent males. They may also occur outside the nasopharynx
      (ENA) and can therefore be misdiagnosed. An ill-advised biopsy may result in
      brisk bleeding. This study was undertaken to evaluate the incidence and clinical
      features of ENA. MATERIAL AND METHODS: A review of the international literature
      was performed. RESULTS: A total of 65 patients with ENAs from 16 different
      countries were reported in the literature. Two patients had a congenital lesion,
      the oldest being 78 years old. A total of 48 patients were male (73%). The
      maxilla was the most commonly affected site (24.6%), with the ethmoid, nasal
      cavity or septum and other sites being involved less frequently. Symptoms arose
      in 40 patients within 6 months. Among a wide variety of symptoms, epistaxis with
      or without nasal obstruction was reported for 18 patients. Brisk bleeding
      resulting from a total of 23 biopsies occurred in 13 patients, and required blood
      transfusion in 11. Death was reported for two patients as a result of acute
      respiratory compromise and endocranial extension. CONCLUSION: ENAs are extremely
      rare compared to NAs and have to be acknowledged as a different entity. In
      comparison to patients with NAs, as female adults are affected, the lesion is
      diagnosed earlier and is less vascularized and the patients are older. Surgical
      resection is sufficient treatment due to a tendency for local and less aggressive
      growth.

PMID- 15513522
TI  - Effect of 17 beta-estradiol on diastrophic dysplasia sulfate transporter activity
      in otosclerotic bone cell cultures and SaOS-2 cells.
AB  - OBJECTIVE: Diastrophic dysplasia sulfate transporter (DTDST) is involved in the
      regulation of bone turnover, and its activity in otosclerosis has been shown to
      be abnormally high. Taking into account the role of estrogens in the progression
      of otosclerosis, the possible effect of estrogens on DTDST was investigated in
      otosclerotic bone cell cultures and in SaOS-2, a human osteoblastic cell line.
      MATERIAL AND METHODS: Primary bone cell cultures of stapes and external auditory
      canal (EAC) bone were obtained from 33 patients with otosclerosis and 18 control
      patients undergoing cerebellopontine angle tumor surgery. These cultures were
      assessed in parallel with SaOS-2 cells. Estrogen receptors (ERs) were detected
      using reverse transcriptase polymerase chain reaction. DTDST activity was
      assessed by sulfate uptake at baseline and after 24 h of incubation with 17 beta
      estradiol at concentrations ranging from 10(-12) to 10(-6) M. RESULTS: Stapes and
      EAC cultures predominantly expressed mRNA of ER alpha, while ER beta expression
      was predominant in SaOS-2 cells. In stapes and EAC cultures no modification of
      DTDST activity was observed with 10(-8) M 17 beta-estradiol. In SaOS-2 cells,
      DTDST activity was inhibited by 17 beta-estradiol (93.5+/-9.21 vs 83.6+/-8.83
      pmol/mg protein/5 min, n=29; mean of differences=10.0+/-3.22, paired t-test,
      p<0.01). CONCLUSION: DTDST activity is regulated by estrogens in SaOS-2 cells,
      but not in primary cell cultures from stapes and EAC. This difference in the
      regulation mechanisms may be related to the type of estrogen receptor expressed.

PMID- 15513523
TI  - Effect of salicylate on electrically evoked otoacoustic emissions elicited in the
      first and third turns of the guinea pig cochlea.
AB  - OBJECTIVE: Electrically evoked otoacoustic emissions (EEOAEs) are sounds emitted
      in the ear canal when an alternating current is delivered to the cochlea.
      Salicylate, which causes reversible hearing loss, decreases both the
      electromotility of the outer hair cells (OHCs) and the EEOAE output. The
      frequency response of EEOAEs is known to depend on the location of the
      stimulating electrode. Using electrodes placed in the first or third turn of the
      cochlea, we measured EEOAEs before and after salicylate administration in order
      to clarify the frequency range of EEOAEs from which exact information can be
      acquired. MATERIAL AND METHODS: A sinusoidal electrical signal (160 microA root
      mean-square) at frequencies ranging from 500 Hz to 16 kHz was delivered to the
      first or third turn of the scala tympani of the guinea pig cochlea in order to
      determine EEOAEs. The EEOAE outputs were measured before and every 5 min after
      administration of salicylate (500 mg/kg) for 60 min. The threshold of the
      compound action potential (CAP) was measured before and 60 min after salicylate
      administration. RESULTS: CAP thresholds were reduced at frequencies ranging from
      2 to 12 kHz after salicylate administration. The maximum EEOAE output recorded
      with the first-turn electrode was obtained at 12 kHz with a gentle slope of low
      cutoff, whereas the frequency response of the EEOAE recorded with the third-turn
      electrode demonstrated a steep dip at 2 kHz. CONCLUSION: EEOAE reduction after
      salicylate administration was restricted to frequencies close to that of the
      characteristic frequency (CF) of the electrode position. This was probably
      related to the fact that the EEOAE is the sum of waves from the CF of the
      electrode position and the stimulus frequency. In terms of studying the
      electromotility of OHCs, useful information obtained from EEOAEs is restricted to
      the narrow frequency band close to the CF of the electrode location.

PMID- 15513524
TI  - Endocochlear potential and endolymphatic K+ changes induced by gap junction
      blockers.
AB  - OBJECTIVE: To examine the effects of gap junction blockers on the endocochlear
      potential (EP) and endolymphatic potassium concentration ([K(+)](e)). MATERIAL
      AND METHODS: The EP and [K(+)](e) were monitored using double-barreled ion
      selective microelectrodes in the second turn of the guinea pig cochlea during
      perilymphatic perfusion. RESULTS: When the perilymphatic scalae of the cochlea
      were perfused with artificial perilymph containing 10 mM n-heptanol the EP was
      decreased by -8.8+/-1.4 mV (n=10), and this was accompanied by a decline in the
      [K(+)](e) of -6.7+/-2.1 mM (n=6). Perilymphatic application of 10 mM hexanol also
      produced declines in both the EP and [K(+)](e). In control studies, perilymphatic
      perfusion with 10 mM ethanol showed no remarkable changes in either the EP or
      [K(+)](e). Anoxia during perfusion with heptanol resulted in the generation of a
      negative EP, similar to the situation in controls. CONCLUSIONS: A decline in the
      EP together with a lowering of [K(+)](e) induced by long-chain n-alkanols, which
      act as gap junction blockers, may be explained by an interruption in potassium
      ion transport related to a gap junction dysfunction.

PMID- 15513525
TI  - Distribution of Fos-like immunoreactivity in the auditory pathway evoked by
      bipolar electrical brainstem stimulation.
AB  - OBJECTIVE: The auditory brainstem implant (ABI) represents a new modality for the
      treatment of patients deafened as a result of complete excision of a bilateral
      VIIIth nerve tumor. However, little work has been done on the effect of the ABI
      on the mammalian auditory pathway. The aim of this study was to demonstrate the
      effect of the ABI using Fos-like immunoreactivity. MATERIAL AND METHODS: A
      bipolar electrode was implanted in the dorsal cochlear nucleus of bilaterally
      deafened Sprague-Dawley rats, and electrical stimulation was presented at an
      intensity four times that of threshold. RESULTS: Fos-like immunoreactivity was
      induced in the neurons of various auditory brainstem nuclei and observed in the
      low-to-middle frequency area. In the ipsilateral dorsal cochlear nucleus,
      ipsilateral posterior ventral cochlear nucleus and bilateral inferior colliculus,
      Fos-like immunoreactive neurons were observed as a distinct banding pattern.
      CONCLUSIONS: This study showed that Fos-like immunoreactivity was observed in the
      restricted area of the primary brainstem auditory pathway with the appropriate
      tonotopicity. These results indicate that the ABI can provide auditory
      information suitable for speech recognition.

PMID- 15513526
TI  - Gastroesophageal reflux and sequelae of chronic tubotympanal disorders in
      children.
AB  - OBJECTIVE: To compare sequelae of chronic tubotympanal disorders in children with
      and without gastroesophageal reflux (GER). MATERIAL AND METHODS: In 32 patients
      with chronic tubotympanal disorders GER was studied by means of 24-h continuous
      esophageal pH monitoring. After a period of 2-6 years (mean 4 years) sequelae of
      the tubotympanal disorders were examined, together with the clinical status of
      the ears and hearing status. The criteria for classification into mild, moderate
      and severe sequelae were based on the clinical status of the ear. Hearing was
      determined using tonal audiograms. Conductive hearing loss was classified as
      either slight (< or = 35 dB hearing loss in speech frequencies) or severe (>35 dB
      hearing loss in speech frequencies). RESULTS: In the group of 16 patients (mean
      age 6.1 years) with GER, sequelae were observed in 29 ears (mild, n=11; moderate,
      n=5; severe, n=13). Hearing impairment was determined in 20 ears (mild, n=8;
      severe, n=12). In the group of 16 patients (mean age 7.1 years) without GER,
      sequelae were observed in 17 ears (mild, n=11; moderate, n=1; severe, n=5).
      Hearing impairment was determined in 10 ears (mild, n=6; severe, n=4).
      CONCLUSION: The total number of ears with sequelae and the total number of ears
      with conductive hearing impairment were significantly higher in patients with
      GER.

PMID- 15513527
TI  - Imaging of the patulous Eustachian tube: high-resolution CT evaluation with
      multiplanar reconstruction technique.
AB  - OBJECTIVE: To evaluate the 3D anatomy of the ET and its surrounding tissues in
      cases with or without patulous Eustachian tube (ET) using CT with the multiplanar
      reconstruction (MPR) technique. MATERIAL AND METHODS: Twenty patients with a
      patulous ET and 25 without middle ear problems were investigated. After
      performing a temporal bone CT examination, MPR images of the ET were
      reconstructed and measurements were made. RESULTS: The ET lumen and its
      surrounding tissues were clearly identified. In the patulous ET group, the ET
      lumen was open throughout the cartilaginous portion and the volume of the low
      density area was smaller in size than in the controls. In unilateral patulous ET
      patients, the anatomical features were found to be similar on both sides, in
      spite of the fact that the non-involved side did not show symptoms associated
      with a patulous ET. CONCLUSION: For the first time, we were able to obtain clear
      reconstructed images of the patulous ET and its surrounding structure and to
      study its anatomical features. This method is useful for obtaining a better
      understanding of the ET and ET-related diseases such as patulous ET.

PMID- 15513528
TI  - Micronucleus frequency in acquired middle ear cholesteatoma.
AB  - OBJECTIVE: To determine the micronucleus (MN) frequency of acquired cholesteatoma
      tissue using an MN assay. MATERIAL AND METHODS: Eighteen patients were diagnosed
      as having chronic otitis media with acquired cholesteatoma and were divided into
      primary and secondary acquired cholesteatoma groups. Cholesteatoma tissue and
      normal tissue specimens from the external ear canal skin were taken from the
      patients during surgical operations. MN frequencies of cholesteatoma and control
      samples were determined according to standard criteria. RESULTS: The MN
      frequencies of the cholesteatoma and control tissues were 0.54%+/-0.31% and
      0.24%+/-0.11%, respectively (p<0.01). MN frequencies for the primary and
      secondary acquired cholesteatoma groups were 0.63%+/-0.36% and 0.46%+/-0.26%,
      respectively (p>0.05). MN frequencies in cholesteatoma patients without and with
      complications were 0.42%+/-0.19% and 0.85%+/-0.37%, respectively (p<0.05).
      CONCLUSION: MN frequencies were found to be increased in cholesteatoma tissues
      when compared with external ear canal skin. The MN frequency in five cases with
      complications was higher than in cases without complications. These results
      indicate that there could be associations between MN frequency and acquired
      cholesteatoma and between MN frequency and complications.

PMID- 15513529
TI  - Effect of acute inner ear pressure changes on low-level distortion product
      otoacoustic emissions in the guinea pig.
AB  - OBJECTIVE: To determine a relation between acute inner ear pressure changes and
      cochlear function as measured by low-level 2f(1)-f(2) distortion product
      otoacoustic emissions (DPOAEs). MATERIAL AND METHODS: During and after a change
      in inner ear pressure induced by injection or aspiration of perilymph, the 2f(1)
      f(2) DPOAE at 4.5 kHz generated by low-level primaries was recorded in the guinea
      pig. RESULTS: Large changes in overall inner ear pressure produced only small
      changes in the 2f(1)-f(2) amplitude and phase. During injection of 0.5 microl of
      artificial perilymph into the scala tympani over a 10-s period, the mean inner
      ear pressure increased by approximately 500 Pa, with an accompanying mean
      increase in the 2f(1)-f(2) amplitude of 0.7 dB. During aspiration of 0.5 microl
      of perilymph over a 10-s period, the mean inner ear pressure decreased by
      approximately 700 Pa, with an accompanying mean decrease in the 2f(1)-f(2)
      amplitude of 0.9 dB. Changes in DPOAE amplitude followed inner ear pressure
      changes with a delay of 1-2 s. The magnitude and sign of the amplitude changes
      can (partly) be explained by a change in oval window stiffness. No explanation
      was found for the measured delay. CONCLUSION: Clinically, these experiments can
      be of value in gaining insight into the pathophysiological mechanisms of
      pathological pressure changes as seen in Meniere's disease and perilymphatic
      fistulae.

PMID- 15513530
TI  - Dynamic posturography in humans imagining a fixed spatial reference.
AB  - OBJECTIVE: To investigate the effect of imagining a fixed spatial reference on
      balance control. MATERIAL AND METHODS: Twenty-one healthy subjects were asked to
      remain as stable as possible while standing on a sway-referenced platform
      (NeuroCom Equitest posturography system). Subjects were instructed to keep their
      eyes open in the dark and to either look far into the distance without fixating
      on any particular point in space or to direct their gaze towards a remembered
      earth-fixed target (25-cm distant). Room lights were switched off immediately
      before each 20-s sway recording. Postural stability measures included equilibrium
      scores and root-mean-square sway amplitudes in the anterior-posterior plane.
      RESULTS: Postural sway was not influenced by the instruction to gaze towards a
      remembered target. CONCLUSION: Imagining a fixed spatial reference does not
      influence postural control, at least during sway-referenced dynamic
      posturography.

PMID- 15513531
TI  - Habituation to galvanic vestibular stimulation.
AB  - OBJECTIVE: To examine the response decline that occurs upon repetitive galvanic
      vestibular stimulation (GVS) and hampers long-term clinical evaluations. MATERIAL
      AND METHODS: This was a prospective experimental study conducted in a tertiary
      referral centre. In a previous study we developed a standardized procedure for
      reproducible quantification of galvanic-induced body sway (GBS). The most
      reproducible responses were found using a continuous 1-cosinusoidal stimulus (0.5
      Hz; 2 mA) preceded by a pre-habituating stimulus. This binaural prestimulation
      reduced the short-term (<5 min) response decline to a non-significant level. The
      response decline without prestimulation was interpreted as habituation to the
      galvanic stimulation. In the present study we evaluated possible long-term
      habituation to GVS, which may hamper longitudinal clinical evaluations. Possible
      long-term habituation using the short-term habituating prestimulus concept was
      studied by quantifying GBS in 40 subjects at 5 consecutive time points. Subjects
      were subdivided into four equal groups who were tested with four different time
      intervals between the five measurements, ranging from 1 day to 2 weeks. RESULTS:
      The absolute test results did not vary with the time interval (p=0.217; repeated
      measurement test). Irrespective of the time interval between the tests,
      habituation occurred after the first stimulation and remained stable at all
      consecutive measurements. GVS habituation did not depend on either the degree of
      daily life activity (moderate practice of sport) or on gender. CONCLUSION: The
      current protocol, using a prehabituating binaural stimulus, showed that
      reproducible assessment of the GVS over a time course of days to weeks was
      possible starting from the second test.

PMID- 15513532
TI  - Otologic consequences of blast exposure: a Finnish case study of a shopping mall
      bomb explosion.
AB  - OBJECTIVE: On 11 October, 2002, in the Myyrmanni shopping mall, Vantaa city,
      Finland, an explosion by a suicide bomber killed 7 people and injured at least
      160,44 of whom had ear trauma. We investigated the acute and subacute otologic
      consequences of the explosion. MATERIAL AND METHODS: Otologic examination of the
      29 patients treated for ear trauma at the ENT clinic of the University Hospital
      of Helsinki was performed during the first month after the explosion, and a
      questionnaire was completed regarding subjective aural symptoms. Symptoms
      occurring directly after the explosion and for up to 1 month afterwards were
      assessed. RESULTS: Of the 29 patients, 66% had tinnitus as the initial symptom,
      55% hearing loss, 41% pain in the ears and 28% sound distortion. Tinnitus and
      hearing loss in combination were experienced by 12 patients (41%). Eight patients
      who had been situated<10 m from the center of the explosion had a rupture of the
      tympanic membrane. This supported the initial evaluation by the authorities that
      the bomb had consisted of approximately 3 kg ammonium nitrate, equivalent to
      approximately 0.5 kg of trinitrotoluene. It was estimated that some kind of ear
      injury was likely for individuals situated<70 m from the center of the explosion.
      CONCLUSIONS: People often think that tinnitus and hearing impairment are
      naturally occurring phenomena after blast exposure, and if their symptoms resolve
      they do not seek medical advice. However, some of them may have substantial
      hearing impairment, particularly at high frequencies. Otologic consultation, or
      at least an audiometric screening test to exclude hearing impairment, should be
      performed regardless of symptoms, on the basis of exposure data only. Some
      symptoms, such as tinnitus and hearing loss, may be permanent consequences of a
      blast injury and their effect on quality of life may be substantial.

PMID- 15513533
TI  - Extracellular signal-regulated kinase is involved in tumor necrosis factor-alpha
      induced MUC5AC gene expression in cultured human nasal polyp epithelial cells.
AB  - OBJECTIVES: Mucus secretion and inflammatory cytokines are increased in cases of
      chronic sinusitis with polyp. In this study we initially investigated the
      localization of MUC5AC protein in human nasal polyps. We then examined whether
      tumor necrosis factor-alpha (TNF-alpha) induces MUC5AC gene expression and
      whether extracellular signal-regulated kinase (ERK) plays a role in TNF-alpha
      induced MUC5AC gene expression in cultured human nasal polyp epithelial cells.
      Finally, we investigated whether MUC5AC and activated ERK are co-expressed in
      goblet cells. MATERIAL AND METHODS: Human nasal polyp epithelial cells were
      isolated and subcultured. Passage-2 polyp epithelial cells were treated with 10
      ng/ml TNF-alpha. ERK involvement was determined by Western blotting and MUC5AC
      gene expression by reverse transcriptase polymerase chain reaction. An ERK kinase
      assay and an inhibitor study using PD98059 were also performed.
      Immunohistochemical staining using polyclonal MUC5AC antibody and a phospho
      specific ERK antibody was done in nasal polyps. RESULTS: MUC5AC was found to be
      expressed in the majority of goblet cells in human nasal polyp epithelium. TNF
      alpha induced MUC5AC gene expression, and ERK activation was found to be
      essential for TNF-alpha-induced MUC5AC gene expression in cultured human nasal
      polyp epithelial cells. In addition, both MUC5AC and activated ERK were co
      expressed in goblet cells of human nasal polyp epithelium. CONCLUSIONS: TNF-alpha
      induces MUC5AC gene expression via ERK in cultured human nasal polyp epithelial
      cells.

PMID- 15513534
TI  - Suppression of matrix metalloproteinase production from nasal fibroblasts by
      fluticasone propionate in vitro.
AB  - OBJECTIVE: To examine the influence of fluticasone propionate (FP) on matrix
      metalloproteinase (MMP) production from nasal polyp fibroblasts in vitro.
      MATERIAL AND METHODS: Fibroblasts derived from five nasal polyps were stimulated
      with tumor necrosis factor (TNF)-alpha in the presence of various concentrations
      of FP. The influence of FP on MMP production was assessed by examining the levels
      of MMP-2 and -9 in culture supernatants using ELISA. We also examined the
      influence of FP on MMP mRNA expression using reverse transcriptase polymerase
      chain reaction. RESULTS: The addition of FP caused significant suppression of MMP
      2 and -9 production from nasal polyp fibroblasts in response to TNF-alpha
      stimulation. MMP mRNA expression was also suppressed by the addition of FP to
      cell cultures. The minimum concentration of the agent required to cause
      suppression was 10(-5) M. CONCLUSION: These results suggest that the inhibitory
      action of FP on tissue remodeling may underlie the clinical efficacy of
      corticosteroids in nasal polyposis.

PMID- 15513535
TI  - Palatal implants: a new method for the treatment of snoring.
AB  - OBJECTIVE: To evaluate the safety, feasibility and effectiveness of a treatment
      for snoring using permanent palatal implants. MATERIAL AND METHODS: This was a
      prospective, non-randomized study involving 35 healthy patients (26 males, 9
      females) referred for treatment of habitual snoring. A baseline medical
      examination, an evaluation of snoring-related subjective symptoms and an
      overnight sleep analysis were performed. Three PET implants were placed in the
      palate of each patient using a new delivery device under local anaesthesia. The
      patients were followed by means of office visits at 2-3, 14, 30 and 90 days
      postoperatively, at which discomfort, pain, adverse events and changes in snoring
      related parameters were recorded. RESULTS: The average time required for the
      procedure was 8 min; 23% of the patients required no postoperative analgesia; the
      average consumption of analgesic was 125 mg of diclofenac and the average
      duration of analgesia was 1.5 days after the procedure. No bleeding, haematoma or
      infection were observed. Two of the implants were extruded; both of these
      patients experienced a satisfactory reduction in snoring intensity and no
      replacements were necessary. The mean reduction in snoring intensity was 51%,
      with the visual analogue scale score evaluated by the bed partner falling from
      7.3 to 3.6 (p<0.001). The Epworth Sleepiness Score dropped from 9.3 to 4.6
      (p<0.001). In total, 86% of the bed partners and 89% of the patients recommended
      the procedure. CONCLUSION: The new palatal implant system is safe and is
      associated with low morbidity. It is a fast, simple and effective treatment for
      snoring.

PMID- 15513536
TI  - Laser resection of T1a glottic carcinomas: results and postoperative voice
      quality.
AB  - OBJECTIVES: To calculate recurrence, mortality and complication rates and
      evaluate postoperative voice quality after laser resection of T(1a) glottic
      carcinoma. MATERIAL AND METHODS: Since 1995 we have treated 118 patients with a
      T(1a) glottic carcinoma with laser surgery. In order to evaluate postoperative
      voice quality, patients who were alive and free of recurrence were sent the Voice
      Handicap Index (VHI) questionnaire containing 30 questions concerning how their
      voice affects their daily life physically, emotionally and socially. RESULTS:
      Twelve patients (10%) had a local recurrence and received further treatment,
      either a second laser treatment, radiotherapy or a total laryngectomy. One
      patient (0.84%) died due to the laryngeal cancer. Ninety-nine patients were sent
      the VHI questionnaire and 94 of the completed questionnaires were included in the
      study and analyzed. The mean total score was 13.2, with mean subscores of 6.5
      (physical), 4.1 (functional) and 2.5 (emotional). CONCLUSIONS: The results
      indicate that these patients as a group do not consider that their voice has a
      negative impact on their daily life. Good surgical technique is essential to
      obtain a good functional result. The laser strength should be kept low and the
      surgical margins small in order to minimize scarring and vocal cord stiffness.

PMID- 15513537
TI  - Does unnecessary elective neck treatment affect the prognosis of N0 laryngeal
      cancer patients?
AB  - OBJECTIVE: Among detractors of elective neck (N0) treatments, most suggest that
      lymphadenectomy removes a barrier to the spread of disease with deleterious
      immunologic consequences. To test this hypothesis we performed a retrospective
      comparison of the survival results of N0 laryngeal cancer patients who received
      unnecessary elective neck treatments (N0-) and those of N0 patients subjected to
      close and regular follow-up. MATERIAL AND METHODS: A retrospective chart review
      of 749 N0 laryngeal cancer patients treated at the Institute of Otolaryngology
      Head and Neck Surgery, University of Florence between January 1980 and January
      1993 was performed. Of these, 245 (33%) received elective neck dissection (ED),
      while the remaining 504 (67%) N0 patients were subjected to close and regular
      follow-up (wait-and-see policy; WS). RESULTS: Of the 245 ED patients, 43 (17.5%)
      showed an occult neck disease, while of the 504 WS subjects, 83 (17%) developed
      neck metastases during follow-up. Moreover, 15 ED patients subsequently
      experienced a contralateral occult failure despite a unilateral negative neck
      specimen (N0-). Thus, ultimately 187 ED (164 of whom were treated unilaterally
      and 23 bilaterally) and 421 WS patients were used for survival analysis. No
      differences in terms of postoperative complications, local or distant failure or
      disease-free or overall actuarial survival were found between the two groups
      analyzed. CONCLUSIONS: These data indicate that unilateral or bilateral removal
      of cervical lymphatics in the absence of histologically proven lymph node
      metastases does not negatively affect the prognosis of N0 laryngeal cancer
      patients who were overtreated to the neck.

PMID- 15513538
TI  - Comparison of two stapes prostheses (titanium and fluoroplastic-platinum piston):
      a theoretical point of view.

PMID- 15513539
TI  - Cancer of the larynx in children and adolescents: a neoplastic lesion with a
      different etiology.

PMID- 15513540
TI  - Laryngeal paraganglioma: an updated critical review.
AB  - Laryngeal paragangliomas are rare submucosal lesions that arise from paraganglion
      cells located in the false vocal fold and subglottic larynx. To date, 76
      recognized cases have been reported in the world literature. Symptoms arise when
      the lesions become large enough to impair function. Supraglottic paragangliomas
      cause hoarseness and deglutition disorders, whereas subglottic tumors become
      symptomatic when they obstruct the airway. Evaluation of these tumors includes
      obtaining a complete history. Familial paragangliomas and hypertension should be
      sought but are rarely, if ever, associated with laryngeal paragangliomas. MRI can
      detect these lesions and permit characterization of the vascularity of the
      lesion. Adding 111In pentetreotide scanning can distinguish neuroendocrine tumors
      from other submucosal laryngeal lesions, making the preoperative diagnosis
      clearer and obviating the need for biopsy. The biggest dilemma regarding
      laryngeal paragangliomas is making the correct pathologic distinction between
      paraganglioma, typical carcinoid, atypical carcinoid and medullary thyroid
      cancer. Immunohistochemical markers, supplementing standard histopathologic
      evaluation, can distinguish paragangliomas from the aforementioned tumors. This
      distinction is critical as the prognosis for treated paragangliomas is excellent
      compared to that for other neuroendocrine neoplasms. Almost all alleged malignant
      paragangliomas of the larynx are in reality atypical carcinoid tumors that have
      been misdiagnosed. Treatment should always comprise excision. Thyrotomy has the
      best chance of achieving a sustained cure without damaging phonation or
      deglutition. Laser excision has been used successfully but there is no great
      experience with this modality. Surgery is preferable to radiation for
      paragangliomas in all locations but especially so in the larynx, due to issues
      such as swelling, airway protection and destruction of cartilage. With increased
      clinical suspicion and the use of modern imaging techniques, laryngeal
      paragangliomas should be routinely diagnosed and treated without loss of
      laryngeal functions.

PMID- 15513541
TI  - Intracochlear perfusion of pneumolysin, a pneumococcal protein, rapidly abolishes
      auditory potentials in the Guinea pig cochlea.
AB  - OBJECTIVE: Bacterial meningitis and chronic suppurative otitis media caused by
      Streptococcus pneumoniae are associated with considerable otological morbidity.
      Specifically, sensorineural hearing loss is a permanent sequela in a third of
      those who contract pneumococcal meningitis. Pneumolysin, a pneumococcal protein,
      has been implicated as one of the main virulence/cytotoxic factors. Its
      pathogenicity is intimately dependent on an ability to form transmembrane pores
      on binding with cholesterol in target tissues. MATERIAL AND METHODS: We perfused
      wild-type pneumolysin, at a number of different concentrations, into the guinea
      pig cochlea and used electrocochleography to characterize the effects of this
      cytolytic exotoxin in the organ of Corti. RESULTS: Intracochlear perfusion of
      pneumolysin (10 microg/50 microl) reduced the compound action potential of the
      auditory nerve within seconds. The cochlear microphonics (f1=8 kHz, f2=9.68 kHz)
      and their distortion product (2f1-f2) were also reduced, albeit in a slightly
      less dramatic fashion. At lower concentrations (1 microg/50 microl), a selective
      and earlier effect on inner hair cells was observed. CONCLUSIONS: These results
      clearly show that significant ototoxicity ensues when sensory cells of the organ
      of Corti are exposed to pneumolysin (and complete cochlear death when the
      concentration is high enough). Toxicity is dose-dependent and appears to be site
      sensitive. This may have implications for any possible future protective
      strategies against pneumococcal disease in the ear.

PMID- 15513542
TI  - Acute otitis media caused by drug-resistant bacteria: correlation with antibiotic
      treatment.
AB  - OBJECTIVE: Although acute otitis media (AOM) is the commonest infectious disease
      of childhood, the emergence of drug-resistant bacteria has dramatically changed
      its clinical outcome. Here, we report the trend of AOM due to drug-resistant
      Staphylococcus pneumoniae (DRSP) and beta-lactamase-negative ampicillin-resistant
      Haemophilus influenzae (BLNAR), and the relation between antibiotics used for the
      management of AOM and the isolation of bacterial pathogens. MATERIAL AND METHODS:
      Bacterial isolation and susceptibility tests were performed on specimens from
      children with AOM. Clinical information, including antibiotic treatment within
      the previous 30 days, was analyzed. RESULTS: DRSP was detected in 59.3% of
      Pneumococci isolates and BLNAR in 26.0% of H. influenzae isolates. As expected,
      the incidence of AOM caused by such drug-resistant bacteria has been increasing
      year on year, and 32% of cases have been treated with inappropriate antibiotics.
      In contrast, 32% of cases of AOM caused by DRSP and 50% caused by BLNAR were
      given antibiotics with high susceptibility to drug-resistant bacteria.
      CONCLUSION: In order to ensure the most appropriate use of antibiotics,
      clinicians should consider performing tympanocentesis or myringotomy, with
      subsequent submission of the middle ear fluid for susceptibility testing.
      Furthermore, these results suggest that, as well as the selection of antibiotics,
      the dosage and period of dosing should also be considered in the management of
      AOM. In addition, other factors, in particular horizontal transmission from other
      infants in day care or nursery school, may affect the rapid spread of such drug
      resistant bacteria.

PMID- 15513543
TI  - Galvanic-induced body sway in vestibular schwannoma patients: evidence for
      stimulation of the central vestibular system.
AB  - OBJECTIVE: To investigate the various possible sites of excitation by galvanic
      stimulation by comparing the galvanic-induced body sway (GBS) in vestibular
      schwannoma (VS) patients with that in healthy subjects. MATERIAL AND METHODS:
      This was a prospective experimental study conducted in a tertiary referral
      centre. In a previous study we developed a standardized procedure for
      reproducible quantification of GBS using a monaural continuous 1-cosinusoidal
      stimulus (0.5 Hz; 2 mA). In this study, 23 VS patients were tested before and 12
      VS patients were also tested after surgical intervention (extirpation of tumour
      with concomitant vestibular neurectomy) and the results were compared with those
      obtained in 47 healthy subjects. RESULTS: There were no significant differences
      in mean total GBS gain between VS patients and healthy subjects (p>0.05) before
      surgical intervention. After vestibular neurectomy a significant difference in
      the mean total GBS gain was observed, but GBS was still present after surgery.
      CONCLUSION: These results prove that galvanic vestibular stimulation excites the
      central vestibular system even when conduction via the vestibular nerve is
      hampered.

PMID- 15513544
TI  - Eliciting constant and prominent waves n34-p44 of vestibular-evoked myogenic
      potentials.
AB  - OBJECTIVE: The serial peaks of vestibular-evoked myogenic potentials (VEMPs) have
      been labeled p13, n23, n34 and p44 according to their latency. Waves p13-n23 have
      been shown to be of saccular origin, whereas the origin of waves n34-p44 is still
      unknown. In order to improve the clinical applicability of waves n34-p44, we
      examine the use of different patterns of acoustic stimuli to evoke constant and
      prominent VEMPs, especially waves n34-p44. MATERIAL AND METHODS: In this
      prospective study 27 healthy volunteers (54 ears) underwent VEMP tests. Three
      kinds of click intensity (85, 95 and 105 dB nHL) were presented in a random order
      to evoke 85-VEMP, 95-VEMP and 105-VEMP, respectively. The response rate, latency
      of each peak, peak-to-peak interval and amplitude of waves p13-n23 and n34-p44
      were measured and analyzed. RESULTS: The response rates of waves p13-n23 in 85
      VEMP, 95-VEMP and 105-VEMP were 26% (14/54), 89% (48/54) and 98% (53/54),
      respectively. Significant differences in the response rate existed between 85
      VEMP and both 95-VEMP and 105-VEMP (p<0.01), whereas there was a non-significant
      difference between 95-VEMP and 105-VEMP (p>0.05). In contrast, the response rates
      for eliciting waves n34-p44 were 19% (10/54), 63% (34/54) and 89% (48/54), using
      85, 95 and 105 dB acoustic stimuli, respectively. A significantly higher response
      rate for waves n34-p44 occurred when the intensity of the stimuli increased
      (p<0.01). Although neither latencies nor interval exhibited a significant
      difference between 95-VEMP and 105-VEMP, the amplitude of 105-VEMP was
      significantly greater than that of 95-VEMP for both waves p13-n23 and n34-p44.
      CONCLUSION: An acoustic stimulus intensity of 105 dB nHL is required to reliably
      elicit waves n34-p44 in subjects with normal hearing.

PMID- 15513545
TI  - Preoperative imaging protocol for cochlear implant candidates.
AB  - OBJECTIVE: To formulate and test a CT imaging protocol for preoperative scanning
      of the temporal bone in cochlear implant candidates. MATERIAL AND METHODS: A
      human head was scanned in three CT planes: axial, axiopetrosal and
      semilongitudinal. Multiplanar reformats (MPRs), based on axial slices, were
      created and compared with the corresponding images obtained by direct scanning in
      the respective planes. All scans were analyzed on a viewing workstation. RESULTS:
      The axial plane image allowed for an overview of the temporal bone. The width of
      the facial recess and the cochlear nerve canal could be studied on combined axial
      and axiopetrosal images. Cochlear patency could be evaluated using combined axial
      and semilongitudinal images. Axiopetrosal and semilongitudinal MPRs were able to
      replace the images obtained by direct scanning in the respective planes.
      CONCLUSION: The combination of the axial CT plane image and MPRs was found to be
      sufficient for preoperative analysis of the temporal bone morphology.

PMID- 15513546
TI  - Cochlear implantation in patients with a history of chronic otitis media.
AB  - OBJECTIVE: To propose management options for cochlear implantation in chronic
      otitis media based on our experiences. MATERIAL AND METHODS: A retrospective
      review of 418 cochlear implantations performed by the 2 senior authors between
      November 1988 and February 2004 was conducted. Nine patients who had chronic
      otitis media in the ear to be implanted were included. Of these, three showed
      active inflammation at presentation; the other six cases had undergone previous
      tympanomastoidectomy surgery and did not show active inflammation at
      presentation. RESULTS: Five patients with active inflammation or without an
      adequate soft tissue layer in the mastoid bowl underwent a two-stage procedure.
      Four cases who showed inactive inflammation and had an adequate tissue layer to
      protect the electrode array underwent a single-stage technique, although two of
      them showed dry tympanic membrane perforation. No local or intracranial
      inflammation recurred. The electrode was exposed in the mastoid bowl in one case,
      who was managed with revisional mastoid obliteration with soft tissue.
      CONCLUSION: Complete eradication of inflammation and the securing of a strong
      protective soft tissue layer over the electrode are prerequisites for cochlear
      implantation in ears with chronic otitis media.

PMID- 15513547
TI  - Comparison of the implantability of electronic hearing devices in a virtual
      reality planning environment and in human temporal bones.
AB  - OBJECTIVE: To develop a procedure using a virtual reality (VR) environment that
      permitted us to simulate the preoperative fitting of an electronic implantable
      hearing device (IHD) and assess its implantability. MATERIAL AND METHODS: This
      was an experimental, prospective study based on VR simulations involving the pre-
      and postoperative comparison of the implantability of an IHD. The preoperative
      possibility of implanting an IHD in a VR environment was compared with the
      postoperative implantability of the device in the temporal bones of human
      cadavers and patients. Study groups were analyzed according to the criteria "VR
      implantation" and "real surgery" using contingency tables. RESULTS: A computer
      simulation method based on CT images was developed for the preoperative planning
      of the implantation. The VR simulation proved feasible in all cases (15 temporal
      bones and 24 patients). There was no significant difference between the process
      of implanting the IHD in patients or in the VR environment. These results
      indicate that VR-based test fittings of an IHD allow prediction of the
      implantability of an IHD prior to actual surgery. CONCLUSION: We have described
      the development of a novel VR procedure for predicting the implantability of
      hearing devices in otoneurosurgical applications. The VR procedure can be applied
      universally and may also be used for other parts of the body.

PMID- 15513548
TI  - Vertical canal function in normal subjects and patients with benign paroxysmal
      positional vertigo.
AB  - OBJECTIVES: To assess the dynamics of the vertical semicircular canal (VSCC)
      ocular reflex in normal subjects and then to compare their gain in VSCC-ocular
      reflex with that of patients with benign paroxysmal positional vertigo (BPPV).
      MATERIAL AND METHODS: Subjects were sinusoidally rotated around the earth
      vertical axis with their head tilted 60 degrees backward and turned 45 degrees to
      the right or left side from the sagittal plane at frequencies of 0.1, 0.3, 0.5,
      0.7 and 1.0 Hz with a maximum angular velocity of 50 degrees/s. Head rotation to
      the right side on the right anterior semicircular canal (SCC)-left posterior SCC
      plane or to the left side on the left anterior SCC-right posterior SCC plane
      stimulated the pair of VSCCs. Eye movements were recorded on a video imaging
      system with an infrared charge-coupled device camera, using our new technique for
      analyzing the rotation vector of eye movements in three dimensions. RESULTS: The
      mean gains in left posterior SCC-ocular reflex in normal subjects ranged from
      0.44 at 0.1 Hz to 0.79 at 1.0 Hz, while the mean gains in right anterior SCC
      ocular reflex ranged from 0.45 at 0.1 Hz to 0.73 at 1.0 Hz. The mean gains in
      right posterior SCC-ocular reflex in normal subjects ranged from 0.53 at 0.1 Hz
      to 0.89 at 1.0 Hz, while the mean gains in left anterior SCC-ocular reflex ranged
      from 0.53 at 0.1 Hz to 0.88 at 1.0 Hz. Thus, the gains in VSCC-ocular reflex did
      not differ among the four VSCCs in normal subjects. Similarly, vestibulo-ocular
      reflex (VOR) gains of the four VSCCs in patients with right- or left-sided BPPV
      were almost the same at all frequencies compared to those of normal subjects.
      CONCLUSION: In patients with BPPV, gains in VOR in the four VSCCs were not
      changed in comparison with those of normal subjects. It is suggested that the
      mass of free-floating otoconial debris associated with canalolithiasis was too
      small compared to that of the endolymph to change the canal dynamics.

PMID- 15513549
TI  - Effect of glucocorticoid on upregulation of histamine H1 receptor mRNA in nasal
      mucosa of rats sensitized by exposure to toluene diisocyanate.
AB  - OBJECTIVE: Histamine is a major chemical mediator in the development of nasal
      allergy, which is characterized by nasal hypersensitivity. In this study, we used
      rats sensitized by exposure to toluene diisocyanate (TDI) as an animal model of
      nasal hypersensitivity and examined changes in expression of histamine H1
      receptor (H1R) in the nasal mucosa. The effect of glucocorticoid on upregulation
      of H1R in nasal mucosa induced by TDI was also examined. MATERIAL AND METHODS: In
      rats sensitized by exposure to TDI, nasal allergy-like behavior was scored during
      a 10-min period after TDI provocation. The expression of H1R in the nasal mucosa
      was determined by means of a real-time quantitative reverse transcriptase
      polymerase chain reaction and a [3H]mepyramine binding assay. RESULTS: In TDI
      sensitized rats, nasal allergy-like behavior, such as sneezing and watery
      rhinorrhea, was induced after intranasal application of TDI and nasal
      hypersensitivity to histamine was significantly increased. The level of H1R mRNA
      expression and the specific binding of [3H]mepyramine in the nasal mucosa were
      significantly increased after intranasal application of TDI in TDI-sensitized
      rats. Pretreatment with dexamethasone significantly reduced both nasal allergy
      like behavior and the upregulation of H1R induced by TDI in the rats. CONCLUSION:
      As shown in TDI-sensitized rats, our findings suggest that the upregulation of
      H1R in the nasal mucosa is one of the mechanisms responsible for nasal
      hypersensitivity behavior and nasal hypersensitivity to histamine and that the
      therapeutic effects of dexamethasone are, in part, due to its inhibitory action
      on the upregulation of H1R.

PMID- 15513550
TI  - A daily nasal spray with saline prevents symptoms of rhinitis.
AB  - OBJECTIVE: To ascertain whether a daily nasal spray with physiological saline
      could prevent symptoms of common cold in a population of otherwise healthy
      adults. MATERIAL AND METHODS: This was study involving 10 weeks of daily use of a
      nasal saline spray and 10 weeks of only recording symptoms. Young adults eligible
      for military service at an army barrack in Boden, Sweden were invited to
      participate in the study and 108 healthy conscripts aged approximately 20 years
      agreed to do so. Data were recorded by the participants in a diary at home. In
      the diary the participants noted symptoms such as rhinitis, blocked nose, cough,
      fever and sore throat (pharyngeal pain). They also recorded inability to perform
      their duties due to the symptoms, and any medication or antibiotics necessitated
      by upper respiratory tract infection. RESULTS: A total of 69 subjects completed
      the 20-week diary period. For 60 of them, compliance during the spray period
      exceeded 60% and their data were used in the statistical calculations. During the
      spray period the number of days with nasal secretion and/or blocked nose (mean
      6.4 days) was significantly (p=0.027) lower than that during the observation
      period (mean 11 days). Furthermore, the participants had a mean of 0.7 episodes
      of upper respiratory tract infection during the spray period, compared with 1.0
      episodes during the observation period (p=0.05). CONCLUSION: A daily nasal spray
      with saline can prevent nasal symptoms of common cold in a population of
      otherwise healthy adults.

PMID- 15513551
TI  - Screening of olfactory function using the Biolfa olfactory test: investigations
      in patients with dysosmia.
AB  - OBJECTIVE: To present a statistical evaluation of a new olfactory test, Biolfa.
      MATERIAL AND METHODS: The olfactory test was carried out in individuals with
      normal olfactory function (n=67; 31 males; mean age 27.4 years) and in patients
      with mild, moderate or severe hyposmia (n=155; 61 males; mean age 54.6 years).
      The main diagnoses of the hyposmic patients were upper respiratory tract
      infection (32%), nasal polyposis (24%), head trauma (8%), idiopathic (8%), old
      age (5%) and chronic rhinitis (5%). In the first part of the test, olfactory
      thresholds were measured for three different substances (eugenol, aldehyde C14
      and phenyl ethyl alcohol). The second part comprised an odor identification test
      for determining olfactory function for a large panel of common odors of Southern
      European countries. RESULTS: Mean olfactory thresholds were determined for
      subjects with normal olfaction and hyposmic patients; there was a statistically
      significant relationship between olfactory thresholds and degree of olfaction
      (mild to moderate hyposmia versus severe hyposmia). For the odor identification
      test, a global score was determined to allow the differentiation of normosmic
      subjects from patients with mild, moderate or severe hyposmia. The principles of
      decision theory (i.e. analysis of the receiver operating characteristic curve)
      were applied to the problem of evaluating the ability of Biolfa to distinguish
      subnormal subjects from hyposmic subjects. CONCLUSION: This study provides a
      basis for the routine clinical use of Biolfa.

PMID- 15513552
TI  - Correspondence between three olfactory tests and suprathreshold odor intensity
      ratings.
AB  - OBJECTIVES: The capability of three olfactory tests (European Test of Olfactory
      Capabilities, Sniffin' Sticks and Cross-Cultural Smell Identification Test) to
      similarly classify subjects as normosmics, hyposmics and anosmics as well as the
      relation between test performance and suprathreshold ortho- and retronasal odor
      intensity ratings were examined. MATERIAL AND METHODS: A total of 48 subjects
      (age range 15-84 years; mean age 49.5 years) completed the 3 olfactory tests,
      rated aqueous solutions of vanilla (0-0.31%) and lemon aroma (0-0.17%) for odor
      and flavor intensity and filled in a background questionnaire. Ten subjects had
      case histories indicating anosmia, with the remainder having subjectively normal
      olfaction. RESULTS: The test results were highly correlated and differentiated
      anosmic, hyposmic and normosmic subjects. At an individual level, some
      discrepancy was seen in the olfactory diagnoses given by the three tests. In
      principal component analysis, olfactory measurements were loaded on three
      components: (i) odor detection, discrimination and identification; (ii)
      suprathreshold intensity ratings; and (iii) threshold for n-butanol. Advanced age
      was related to impaired olfactory performance. CONCLUSIONS: Although the three
      olfactory tests diagnosed the individuals slightly differently, all were
      considered to be valid for clinical evaluation of olfactory capabilities. The
      tests separated anosmics and normosmics highly significantly, and permitted an
      assessment of hyposmia. The suprathreshold odor intensity ratings reflected a
      different dimension of olfaction than the three olfactory tests.

PMID- 15513553
TI  - Targeting of a head and neck squamous cell carcinoma xenograft model using the
      chimeric monoclonal antibody U36 radioiodinated with a closo-dodecaborate
      containing linker.
AB  - OBJECTIVE: High rates of local recurrence and distant metastases following
      surgery of high-grade head and neck squamous cell carcinoma (HNSCC) necessitate
      the use of adjuvant systemic treatment. Radioimmunotargeting might be a possible
      treatment modality in this case. The nuclear properties of 131I make it a
      suitable isotope for treatment of minimal residual disease and small metastases,
      but the conventional radioiodine label has poor cellular retention and its
      radiocatabolites accumulate in the thyroid. We attempted to overcome these
      problems by using closo-dodecaborate derivatives for attachment of radioiodine.
      MATERIAL AND METHODS: We investigated the feasibility of targeting an SCC25 HNSCC
      xenograft in vivo using a benzylisothiocyanate derivative of closo-dodecaborate
      (DABI) as radioiodine linker and the chimeric anti-CD44v6 antibody U36. 125I was
      used in biodistribution studies. RESULTS: The use of DABI enabled tumor targeting
      and decreased the radioactivity uptake of the thyroid. CONCLUSION: Tumor
      localization of DABI-labeled U36 was similar to its para-iodobenzoate-labeled
      counterpart, presumably due to the strong dependence of targeting efficiency on
      tumor size.

PMID- 15513554
TI  - Patient contact with healthcare professionals after elective tonsillectomy.
AB  - OBJECTIVE: To assess the amount and causes of patient contact with healthcare
      professionals after elective tonsillectomy. MATERIAL AND METHODS: This was a
      prospective study. All consecutive patients undergoing elective tonsillectomy or
      adenotonsillectomy in 1997 received a questionnaire concerning the post-discharge
      period. RESULTS: A total of 276 patients (93.6%) answered questions regarding
      post-discharge contact. After their discharge, 43.8% of patients contacted
      healthcare professionals. Pain was the leading indication for telephone contact,
      and hemorrhage for visits in person. Information given over the telephone was
      sufficient in 49.5% of cases. Telephone contact was followed by a visit in person
      in the case of hemorrhage in 88.9% of patients and in the case of pain in 34.1%.
      Contact was made most frequently in the older age groups. CONCLUSIONS: Although
      the patients repeatedly received both written and oral information, nearly half
      of them still contacted healthcare professionals during the recovery period.
      Frequent post-tonsillectomy contact should be taken into account when the
      financial and personnel resources of day surgery units are evaluated. In order to
      reduce the amount of post-tonsillectomy contact with healthcare professionals,
      careful attention must be paid to the quality of patient counseling prior to
      discharge.

PMID- 15513555
TI  - Ganglion cells in the posterior cricoarytenoid muscle of the rat following
      experimental denervation.
AB  - OBJECTIVE: To investigate morphological changes of the i.m. ganglion cells in the
      posterior cricoarytenoid (PCA) muscle of the rat following denervation of the
      recurrent laryngeal nerve. MATERIAL AND METHODS: The recurrent laryngeal nerve on
      the left side of the rat was resected. Three weeks after transection, the PCA
      muscle was removed for morphological study using light and electron microscopy.
      RESULTS: No morphological changes were found in the i.m. ganglion cells in the
      PCA muscle, even though the myelinated nerve fibers were destroyed and had
      disappeared in ramified i.m. bundles. Around the cell body, numerous non
      myelinated nerve fibers were found; these contained a large number of clear,
      spherical synaptic vesicles approximately 50 nm in diameter and several dense
      cored vesicles approximately 100 nm in diameter. In contrast, neuromuscular
      junctions in most muscle fibers with partially disoriented and/or disintegrated
      myofibrils showed degenerative figures. In some instances, however, multiple
      nerve terminals were detected in contact with the postsynaptic membrane. Like the
      varicose swellings of non-myelinated nerve fibers around the ganglion cell body,
      these nerve terminals contained, in addition to clear synaptic vesicles (50 nm in
      diameter), several dense-cored vesicles (100 nm in diameter). CONCLUSION: We
      suggest that i.m. ganglion cells in the rat PCA muscle may supply postganglionic
      nerve fibers to the denervated neuromuscular junctions after transection of the
      nerve.

PMID- 15513556
TI  - Distribution of lymph nodes in the neck in cases of tuberculous cervical
      lymphadenitis.
AB  - OBJECTIVE: To investigate the distribution of lymph nodes in the neck during the
      process of development of tuberculous cervical lymphadenitis (TCL) in patients
      attending an outpatient clinic over a 1-year period. MATERIAL AND METHODS: This
      was a prospective, cross-sectional, observational study which included 100 cases
      of histopathologically confirmed TCL of >6 weeks duration. RESULTS: Lymph nodes
      in the posterior triangle (PT) were found to be commonest (51%), followed by
      those in the upper deep cervical (UDC; 48%) and submandibular (SM; 36%) regions.
      The supra-clavicular (SC; 3%), submental (Sment; 4%) and lower deep cervical
      (LDC; 9%) regions were found to be the least frequently affected. Uni- and
      bilateral disease were observed in 83% and 17% of patients, respectively. A
      single group of lymph nodes was involved in 68% of patients, 2 groups in 29% and
      >2 groups in 13% of patients. CONCLUSIONS: These results indicate that if
      unilateral, painless, enlarged and mated lymph nodes are found in either the PT
      or the UDC or SM areas, lymphadenitis of tuberculous origin should be suspected
      rather than lymphadenitis of any other etiology.

PMID- 15513557
TI  - Vascular malformation (so-called hemangioma) of Scarpa's ganglion.
AB  - Vascular malformations of the cerebello-pontine angle (CPA) arising from the
      capillary plexus surrounding Scarpa's ganglion are rare tumors. We report a case
      of so-called "hemangioma" of the CPA which was operated on via a trans
      labyrinthine approach based on a preoperative diagnosis of vestibular schwannoma.
      Although there are some differences between these tumors in terms of the
      clinical, biological and especially MRI findings, surgery is usually performed
      based on an assumption of vestibular schwannoma. Surgery is the treatment of
      choice for these lesions as early intervention ensures better postoperative
      facial function. It is important to make the differential diagnosis if
      conservative management of vestibular schwannoma is adopted.

PMID- 15513558
TI  - Management and follow-up of localized Wegener's granulomatosis: a review of five
      cases.
AB  - OBJECTIVE: To evaluate the complications, efficacy of surgical treatment and
      outcome in patients with the localized form of Wegener's granulomatosis (WG).
      MATERIALS AND METHODS: We reviewed a series of 5 patients (3 males, 2 females;
      age range 22-67 years; mean age 44.6 years) with WG in the upper and lower
      respiratory tracts. RESULTS: Aural, nasal and ocular complications were common in
      our patients. All patients responded to standard immunosuppressive treatment, and
      all surgical treatments had a favorable outcome in the remission stage. Although
      there was no life-threatening disease activity during the course of treatment,
      minor relapses occurred in three patients. CONCLUSIONS: Patients with localized
      WG may have a better outcome than those with systemic WG, but complications due
      to the disease or medication must be actively managed. Reconstructive surgery for
      patients with WG is safe and effective during the remission stage.

PMID- 15513559
TI  - Effect of tonsillectomy in patients with pustulosis palmaris et plantaris.

PMID- 15513562
TI  - The world's children--the children's world. The Rosen von Rosenstein award.
AB  - I feel very honoured to have been selected for the Nils Rosen von Rosenstein
      award. My thanks are due to the Swedish Paediatric Society.

PMID- 15513563
TI  - Tobacco--enemy of public health from conception to grave.
AB  - Parental smoking and the pregnant mother or infant exposure to environmental
      tobacco smoke (ETS) is connected with extraordinarily adverse health consequences
      for the foetus and child. This morbidity and even mortality is preventable.
      CONCLUSION: From the perspective of the foetus and the child, every measure
      should be taken to promote smoking cessation by their parents and prevent
      exposure to ETS.

PMID- 15513564
TI  - Behavioural outcome of regulatory problems in infancy.
AB  - Infant regulatory problems at 3 mo of age and later hyperkinetic problems in
      childhood were evaluated in a prospective longitudinal study. CONCLUSION: There
      was a less favourable long-term behavioural outcome in children with multiple
      regulatory problems. However, family adversity clearly outweighed infant
      regulatory problems as a predictor of hyperkinetic symptoms.

PMID- 15513565
TI  - Caring for the health and medical and emotional needs of children of migrants and
      asylum seekers.
AB  - Political turmoil, military conflicts and other international sociological
      upheavals are causing significant immigration of large numbers of people,
      including infants and children, in Europe. Many of these young migrants are
      refugees. These youngsters have significant health needs, and medical conditions
      (such as infectious diseases) and mental health problems due to their previous
      stressful situations and the difficulties that they often experience while
      settling, even temporarily, into their new environments. Government authorities
      must screen for transmissible diseases and ensure that vaccine-preventable
      infections are adequately covered. Paediatricians must give the best possible
      care for these children and act as their advocates. This can be enhanced by
      collaborating with national and international paediatric societies and with
      international non-government agencies. This problem is not confined to Europe;
      world-wide, it occurs on a massive scale and causes huge burdens for poorer
      countries that have serious difficulties in coping with the extra financial,
      personnel and infrastructure needs imposed by massive, uncontrolled migration of
      populations that are often unhealthy and inadequately nourished. However, this
      should not be used as a pretext to deny safe refuge to children and their
      families who need it. CONCLUSION: Massive movements of infant and child
      immigrants and refugees across European borders over recent years have brought
      challenges to paediatricians because of the needs for the health and medical and
      mental health care of these young people. Paediatricians have an important role
      in their care and by acting, wherever possible, as their advocates. This is a
      massive problem, world-wide, in which paediatricians can have a potentially
      significant positive impact.

PMID- 15513566
TI  - Gastrointestinal manifestations in Henoch-Schonlein purpura: a review of 261
      patients.
AB  - AIM: Henoch-Schonlein purpura is an IgA-mediated autoimmune vasculitis of
      children. It often presents with symptoms including purpuric rash, abdominal
      pain, renal involvement or arthritis. Abdominal pain is a frequent symptom in
      children with HSP and raises the suspicion of intussusception or perforation. We
      sought to evaluate abdominal pain via stool occult blood and image studies.
      METHODS: A retrospective study of 261 patients diagnosed with Henoch-Schonlein
      purpura from December 1991 to December 2001 was conducted. Image studies,
      including abdominal echo, abdominal CT and panendoscopy, were performed for
      patients who suffered from abdominal pain. RESULTS: Of the 261 patients, 151
      (58%) had abdominal pain, and 46 (17.6%) suffered either overt gastrointestinal
      bleeding or had positive stool occult blood. Seven patients had gross bloody
      stools. One acute intussusception and one bowel perforation were noted. One
      patient suffered from hypovolemic shock due to massive gastrointestinal bleeding.
      When stool occult blood was 3+ or 4+, the incidence of a positive image finding
      was high. CONCLUSION: We found that stool occult blood and image studies may be
      necessary regarding severe gastrointestinal involvement. Ultrasonography is an
      important tool when intussusception or bowel perforation is suspected. Monitoring
      the vital signs is important, especially in patients with massive
      gastrointestinal bleeding.

PMID- 15513567
TI  - High prevalence of cagA and vacA seropositivity in asymptomatic Bangladeshi
      children with Helicobacter pylori infection.
AB  - AIM: To evaluate the prevalence of antibodies against two major markers of
      virulence of Helicobacter pylori--cytotoxin-associated gene A (cagA) and the
      vacuolating cytotoxin gene (vacA)--among children in a peri-urban community of
      Bangladesh, and to evaluate Western blot (WB) assay for detection of H. pylori
      infection diagnosed by 13C urea breath test (UBT) in such children. METHODS: One
      hundred and eighty-two children aged 18-60 mo, of the peri-urban community of
      Dhaka, were screened for H. pylori infection using UBT, and the serum samples
      were analysed for antibody against cagA and vacA by Western blot. RESULTS: The
      overall prevalence of H. pylori infection by 13C-urea breath test was 80%. The
      seroprevalence of cagA with or without vacA, vacA with and without cagA, and both
      cagA and vacA were 82%, 82% and 81%, respectively. Among children with a positive
      UBT, 95% were seropositive for both cagA and vacA, indicating that the products
      of these genes are frequently co-expressed in H. pylori infection in this
      community. The sensitivity, specificity, positive and negative predictive value
      of the Western blot test for H. pylori infections, compared to UBT, were 94%,
      68%, 92% and 76%, respectively. CONCLUSION: Compared to UBT, Western blot test is
      reliable for the detection of H. pylori infection. The high seroprevalence of
      cagA- and vacA-positive virulent H. pylori strains in an asymptomatic paediatric
      population indicate that such strains are common in this population and may cause
      characteristic H. pylori infection in Bangladesh.

PMID- 15513568
TI  - Vitamin A for acute respiratory infection in developing countries: a meta
      analysis.
AB  - AIM: To determine the efficacy of intervention with high-dose vitamin A as an
      adjunct to standard treatment on outcome in acute lower respiratory tract
      infection in children in developing countries. METHODS: A systematic review of
      double-blinded, randomized, controlled intervention studies of high-dose vitamin
      A or placebo in children aged between 1 mo and 6 y presenting with acute non
      measles lower respiratory tract infection. RESULTS: Five studies fulfilling the
      criteria were identified and included a total of 2177 children (1067
      intervention, 1110 control). The main outcome measures were time to normalization
      of fever, respiratory rate and oxygen dependence, time to discharge, and
      mortality. On meta-analysis, there were no significant differences in any of the
      recovery measures or mortality between the intervention and control groups.
      Pooled results for recovery times are given showing difference in days to
      recovery days and 95% confidence intervals. Positive summary measures indicate
      faster recovery in the vitamin A group and negative in the placebo: fever: 0.03 (
      0.10 to 0.17); oxygen requirement: -0.08 (-0.31 to 0.16); raised respiratory
      rate: -0.09 (-0.38 to 0.19); hospital stay: -0.06 (-0.52 to 0.40). Mortality was
      below 2% in both groups, with a non-significantly higher risk in the intervention
      group (odds ratio 1.16, 95% CI: 0.61-2.21). CONCLUSION: There is no evidence from
      this meta-analysis that intervention with high-dose vitamin A improves recovery
      from pneumonia in children in developing countries aged from 1 mo to 6 y.

PMID- 15513569
TI  - Randomized controlled trial of intrapleural streptokinase in empyema thoracis in
      children.
AB  - AIM: To compare intrapleural streptokinase and placebo in paediatric empyema.
      METHODS: Children with empyema greater than stage 5 received intrapleural
      streptokinase (n = 19) or normal saline (n = 21) along with intercostal drainage.
      Clinical and serial sonographic outcomes were compared. RESULTS: Although there
      was no difference in clinical and sonographic outcome, none of the children with
      stage 7 empyema (multi-loculated empyema) who received streptokinase developed
      pleural thickening 30 d later. CONCLUSION: There is no short-term clinical
      benefit of intrapleural streptokinase in paediatric empyema; this therapy may be
      reserved for those with stage 7 empyema to prevent pleural thickening in the long
      term.

PMID- 15513570
TI  - Endogenous glucose production and lipolysis in anorexia nervosa--a study using
      stable isotope-labelled compounds.
AB  - Glucose production and lipolysis were investigated in teenage girls with anorexia
      nervosa using glucose and glycerol labelled with stable isotopes. The production
      of energy substrates were also maintained in the very underweight patients who
      showed higher relative rates of substrate mobilization compared to those who had
      gained some weight. CONCLUSION: The investigation shows that glucose production,
      necessary to provide fuel for the central nervous system, is also maintained in
      starving patients with anorexia nervosa.

PMID- 15513571
TI  - Weight requirements for return of menstruations in teenage girls with eating
      disorders, weight loss and secondary amenorrhoea.
AB  - AIM: To investigate the weight requirements for return of menstruation in teenage
      girls with eating disorders (ED), weight loss and secondary amenorrhoea. METHODS:
      Growth charts from the school health services and measurements of weight and
      stature at assessment and during follow-up were obtained for 127 girls with ED,
      secondary amenorrhoea and subsequent return of menstruation. Measurements were
      used to estimate weight and body mass index (BMI) before puberty, at menarche, at
      the highest weight prior to the onset of the ED, at the last menstruation
      preceding amenorrhoea, at the lowest weight during treatment, and at return of
      menstruation. RESULTS: Before onset of the ED, the girls were taller, heavier and
      less lean than the population average as evidenced by standard deviation scores
      (SDS) for weight, height and BMI above zero. Weight loss started from an average
      weight of 58.9 +/- 9.8 kg (mean +/- SD), a last menstruation occurred at 51.5 +/-
      6.9 kg, the lowest weight during treatment was 45.6 +/- 7.0 kg and menstruation
      returned at 52.9 +/- 6.0 kg. Return of menstruation occurred within a wide weight
      range. However, if weight at return of menstruation was expressed in SDS, it
      could be predicted by a linear regression on weight SDS at loss of menstruation
      (r2 = 0.76; p < 0.001). CONCLUSIONS: The weight level required for return of
      menstruation is highly individual but can be predicted by the weight at which
      menstruations cease. In the treatment of ED, there is a need for such individual
      weight targets--a target based on the population weight for height and/or age may
      be too generalized and too low.

PMID- 15513572
TI  - Final height after combined growth hormone and GnRH analogue treatment in adopted
      girls with early puberty.
AB  - BACKGROUND: Girls adopted from developing countries often have early or
      precocious puberty, requiring treatment with gonadotrophin-releasing hormone
      (GnRH) analogues. During such treatment, decreased growth velocity is frequent.
      AIM: To study whether the addition of growth hormone (GH) to GnRH analogue
      treatment improves final height in girls with early or precocious puberty.
      METHODS: Forty-six girls with early or precocious puberty (age < or =9.5 y)
      adopted from developing countries were randomized for treatment for 2-4 y with
      GnRH analogue, or with a combination of GH and GnRH analogue. RESULTS: During
      treatment, the mean growth velocity in the GH/GnRH analogue group was
      significantly higher compared to the control group. Combined GH/GnRH analogue
      treatment resulted in a higher final height: 158.9 cm compared to 155.8 cm in the
      GnRH analogue-treated group. Three out of 24 girls (13%) in the combined group
      and nine of the 22 girls (41%) treated with GnRH analogue alone attained a final
      height below -2 standard deviation scores (SDS). CONCLUSION: The difference
      between the two groups is statistically significant, and possibly of clinical
      importance. A future challenge is to identify a subgroup with clinically
      significant advantage of GH addition to GnRH analogue treatment. Being very short
      on arrival in Sweden and being short and young at start of treatment are possible
      indicators.

PMID- 15513573
TI  - Are regulatory problems in infancy precursors of later hyperkinetic symptoms?
AB  - AIM: To examine whether regulatory problems in infancy predict later hyperkinetic
      symptoms in childhood and pre-adolescence. METHODS: In a prospective longitudinal
      study of 319 children at risk of later developmental problems and
      psychopathology, hyperkinetic behaviour problems were assessed at the ages of 2,
      4.5, 8 and 11 y by means of a standardized parent interview. Infant regulatory
      problems at the age of 3 mo were determined from multiple sources of information.
      An observational procedure was used to assess the quality of mother-infant
      interaction. RESULTS: At the age of 3 mo, 17% of the infants (n = 55; 27 boys, 28
      girls) suffered from multiple regulatory problems. Compared to a control group (n
      = 264), these children presented more hyperkinetic symptoms throughout childhood.
      Negativity in the mother-infant interaction and early family adversity each
      contributed to later hyperkinetic symptoms. When controlling for family
      adversity, the association between infant multiple regulatory problems and later
      hyperkinetic problems was rendered insignificant. CONCLUSIONS: These findings
      suggest that multiple regulatory problems may not be a key variable for later
      hyperkinetic problems. The impact of early family adversity factors clearly
      outweighed that of infant psychopathology on later behaviour disorder.

PMID- 15513574
TI  - Appropriate prophylaxis with restrictive palivizumab regimen in preterm children
      in Sweden.
AB  - AIM: Palivizumab (Synagis) was registered in Sweden in 1999 for prophylaxis
      against respiratory syncytial virus (RSV) in premature infants. The high costs
      and the limited knowledge of the efficacy of this substance have led to debate
      about how and when it should be used. National guidelines for the use of
      palivizumab in Sweden were constructed in the year 2000. The aim of this study
      was to evaluate the guidelines. METHODS: A nation-wide prospective study was
      conducted during the two RSV seasons of the years 2000-2002. The paediatric
      departments in Sweden reported the use of palivizumab, the indication for its
      use, and the number of infants born preterm before 36 wk of gestation and less
      than 2 y old who were admitted to hospital for RSV infection. RESULTS: During the
      two seasons, 218 (3.8%) children who were born before 36 wk of gestation, and 97
      (5.4%) who were born before 33 wk, were hospitalized because of RSV infection.
      Five children were treated with mechanical ventilation. No death caused by RSV
      was reported. A total of 390 children were treated with palivizumab, and 16
      (4.1%) of those who received prophylactic treatment were admitted to hospital
      with RSV infection. CONCLUSION: We consider the comparatively restrictive Swedish
      recommendations to be safe and recommend that palivizumab should also be used
      very restrictively in the future. In our opinion, palivizumab in preterm children
      could be recommended only for those with chronic lung disease younger than 1 y of
      age, and with active treatment for their disease.

PMID- 15513575
TI  - Milk consumption during pregnancy and infant birthweight.
AB  - AIM: To examine the risk of low birthweight (<2500 g, LBW), intrauterine growth
      retardation (IUGR) and preterm birth (gestational age <37 wk) in relation to milk
      intake. METHODS: Observational study in southeast Sweden. Questionnaires were
      used to collect data on milk consumption during pregnancy and infant birthweight
      from mother-infant pairs during a 2-y period as part of the ABIS (All Babies in
      Southeast Sweden) study. Data on IUGR were obtained through the Swedish medical
      birth registry. RESULTS: Adjusting for confounders, low milk intake during
      pregnancy was associated with an increased risk of IUGR (p = 0.019; n = 12880).
      LBW (p = 0.191) and preterm birth (p = 0.921) were not associated with milk
      intake during pregnancy. CONCLUSION: This study indicates that low milk intake in
      the pregnant mother may be associated with IUGR of the newborn. We cannot exclude
      the possibility that the correlation found between milk consumption and
      intrauterine growth may be due to undetected confounders. Hence, further research
      is needed to evaluate the relationship between low milk intake, birthweight and
      risk of IUGR.

PMID- 15513576
TI  - Effects of maternal cigarette smoking and cocaine use in pregnancy on fetal
      response to vibroacoustic stimulation and habituation.
AB  - BACKGROUND: Cigarette smoking and cocaine use in pregnancy are common in the US
      and both are risk factors for sudden infant death syndrome (SIDS). Although the
      cause of SIDS is not known, one postulated mechanism involves abnormalities of
      arousal and arousal regulation. Cigarette smoking and cocaine use may cause
      deficits of arousal. Many believe arousal deficits occur prenatally. AIMS: The
      aim of this study was to assess the effects of cigarette smoke and cocaine
      exposure during pregnancy on measures of fetal arousal and arousal competency: 1)
      the fetal response to vibroacoustic stimulation (VAS) and 2) habituation to VAS.
      HYPOTHESIS: Maternal cigarette smoking and cocaine use in pregnancy are
      associated with altered arousal and arousal regulation in the fetus. METHODS:
      Three groups of mother-fetal dyads were enrolled: 1) cigarette smokers (n = 54),
      2) cocaine users (n = 30), and 3) controls (n = 60). One hundred eight fetuses
      were tested at 29-31 wk gestation, 119 at 32-35 wk, and 118 at 36+ wk. The fetal
      response to VAS was assessed using real-time ultrasound and a paradigm of arousal
      responsiveness. Responders were tested with repeated VAS to assess habituation.
      Also, the quality of fetal reactivity to repeated stimuli was assessed as a
      measure of arousal and arousal regulation competence (Behavioral Reactivity
      Scale). RESULTS: The control group had a larger proportion of fetuses who were
      too active to initiate testing ("too active to test") (p = 0.013); the proportion
      of fetuses too active to test decreased with increasing gestational age. The
      majority of the fetuses who could be tested responded to the initial VAS, and
      there were no group differences. The proportion of fetuses that habituated and
      the rate of habituation did not differ between the groups. Behavioral reactivity
      did not differ between groups. CONCLUSIONS: The original hypotheses were not
      confirmed. However, the chosen assessment paradigms may have lacked sensitivity.
      The proportion of fetuses that were "too active to test" decreased with
      gestational age. The control group had a larger proportion of fetuses that were
      "too active to test" compared with the exposure groups. We speculate that these
      findings indicate that prenatal exposure to these neuroteratogens may have
      produced an acceleration of the behavioral response to vibroacoustic stimulation.

PMID- 15513577
TI  - The value of Bilicheck as a screening tool for neonatal jaundice in term and near
      term babies.
AB  - AIMS: To determine the accuracy of Bilicheck in assessing serum bilirubin. To
      evaluate the effectiveness of Bilicheck as a screening device in a population of
      jaundiced term and near-term babies. METHODS: Prospective evaluation of paired
      Bilicheck measurements and serum bilirubin in 300 babies. RESULTS: There was a
      strong correlation between Bilicheck and serum bilirubin. The mean difference
      between Bilicheck and serum bilirubin was -10.7 micromol/l, but the 95% limits of
      agreement were wide at -80 micromol/l to +60 micromol/l. Bilicheck identified
      significant jaundice (serum bilirubin above 250 micromol/l) with a sensitivity
      (95% confidence interval) of 91% (88% to 94%) and specificity of 66% (60% to
      71%). The area under the receiver operator characteristic curve was 0.85. There
      were five false negatives, all of whom had a serum bilirubin below 300
      micromol/l. If Bilicheck had been used as a screening device, there would have
      been a 55% decrease in blood samples taken in these babies. CONCLUSION: Bilicheck
      cannot be used to measure serum bilirubin in term and near-term babies with
      jaundice, but is an effective screening method, which can be used to safely
      reduce the number of blood tests in these babies.

PMID- 15513578
TI  - Assessment of jaundice in preterm neonates: comparison between clinical
      assessment, two transcutaneous bilirubinometers and serum bilirubin values.
AB  - AIM: 1) To compare the clinical assessment of craniocaudal progression of
      jaundice and two transcutaneous bilirubinometers with serum bilirubin values in
      preterm neonates; 2) to identify factors affecting the difference between non
      invasive bilirubin estimation and serum bilirubin. METHODS: Serum bilirubin was
      clinically estimated in healthy preterm newborn infants (34 to 36.9 gestational
      weeks) independently by a primary investigator and by nurses, and subsequently
      compared with separate measures of two transcutaneous bilirubinometers. RESULTS:
      A total of 107 measurements were performed on 69 infants. Minolta JM-102 showed
      the best performance, with ROC area under the curve of 0.96, followed by
      BiliCheck over the sternum (0.89) and over the forehead (0.88), clinical
      assessment by nurses (0.73) and by a physician (0.70). Serum bilirubin >190
      micromol/l can be detected with 95% sensitivity with Minolta JM-102 > or =19
      units, with BiliCheck > or =145 micromol/l over the sternum and > or =165
      micromol/l over the forehead and with jaundice progression to the trunk or
      further (Kramer zone > or =2). Gestational age affects all non-invasive methods
      in the estimation of serum bilirubin, whereas skin colour affects both BiliCheck
      and clinical assessment. Ambient light affects only clinical assessment.
      CONCLUSION: Minolta JM-102 showed the best performance, closely followed by
      BiliCheck, with clinical assessment performing far worse than either
      transcutaneous method. None of the three methods are recommended as complete
      substitutes for serum bilirubin values in jaundiced preterm infants.

PMID- 15513580
TI  - How do paediatricians communicate with children and parents?
AB  - AIM: The outpatient clinic visit is the major focus of the hospital medical
      process for most paediatricians, children and parents. The importance of children
      as active participants in this interaction has been recognized. Our study aims
      are to describe and assess the components of doctor-parent-child communication in
      the outpatient setting. METHODS: Fifty-one medical paediatric clinic
      consultations were recorded on audio cassette, and communication was analysed
      according to quantitative methods. Questionnaires assessed parents' and
      children's perceptions. RESULTS: Doctors contributed most to the conversation
      (61%), children only 4%. Behaviour: Doctors' communication was 84% instrumental
      (e.g. asking questions, giving information or instructions), 13% affective
      behaviour (expressing concerns and worries) and 3% social (small talk). Parents'
      communication included giving information (83%), seeking information (13%) and
      social (4%). The child asked less information (3%) and had more social
      conversation (19%). CONTROL: Doctors dominated in turn taking (52%). Children
      took 9% of all turns. Perception: There was no correlation between parents' and
      children's perception and the informative or affective behaviour of the doctor.
      CONCLUSION: Communication is mainly instrumental. Doctors tend to direct the
      interview. Children's contribution is small. The participation of children needs
      to be encouraged as part of a patient-centred approach.

PMID- 15513579
TI  - Concentrations of IL-10 in preterm human milk and in milk from mothers of infants
      with necrotizing enterocolitis.
AB  - BACKGROUND: Despite the protective effects of human milk against necrotizing
      enterocolitis, the incidence is highest in the extremely premature infant, and
      only minimally decreased with feeding human milk. This suggests that certain
      protective agents may be lower in milk from mothers delivering extremely
      premature infants. The anti-inflammatory cytokine IL-10 was one possibility. AIM:
      We hypothesized that low concentrations of IL-10 in preterm milk contribute to
      the development of necrotizing enterocolitis in extremely premature infants.
      METHODS: IL-10 in human milk collected at weeks 1, 2, and 4 postpartum was
      measured by ELISA in mothers of infants born extremely premature at 23-27 wk
      gestation (group EP), premature at 32-36 wk gestation (group P), and term at 38
      42 wk gestation (group T). Single milk samples were collected from a separate
      group of mothers whose infants developed necrotizing enterocolitis. RESULTS:
      There were no significant differences in concentrations of milk IL-10 among
      groups EP, P, or T. Concentrations of IL-10 declined as lactation progressed (p <
      0.001). IL-10 in milk was frequently undetected in all groups, but even more so
      in the milk of the group of women whose infants had necrotizing enterocolitis
      (86%) than in groups EP (40%) and P (27%) (p < 0.01). CONCLUSION: IL-10 was
      present in preterm milk from most women, and the concentrations in preterm and
      term milk were not significantly different. A paucity of IL-10 in human milk was
      found in certain mothers in each group, especially in those whose infants
      developed necrotizing enterocolitis.

PMID- 15513581
TI  - Cognitive and neuropsychological functioning in transnationally adopted juvenile
      delinquents.
AB  - AIM: To evaluate cognitive and neuropsychological abilities of adopted delinquent
      adolescents in institutional care. METHODS: Transnationally adopted adolescents
      admitted to institutional care (n = 20) and non-delinquent controls who were also
      transnationally adopted (n = 21) were compared concerning the Wechsler
      Intelligence Scale for Children and Adults (WISC and WAIS), the Wisconsin Card
      Sorting Test (WCST) and the Tower of London test (TOL). The adoptive parents
      answered questions about the adoption, early childhood and family circumstances
      by a questionnaire sent by mail. RESULTS: The adopted delinquents had a
      significantly lower IQ and significantly lower results on several other
      measurements in the WISC/WAIS compared to the controls even after adjustment for
      age of arrival in the adoptive home. Both groups of adoptees scored low in the
      WISC/WAIS subscale of arithmetics when compared to the population mean. The TOL
      test showed that the delinquents were slower and made more errors than the
      controls. CONCLUSION: The delinquent adoptees scored significantly lower on many
      variables in the WISC/WAIS. Both delinquent and non-delinquent adoptees had some
      difficulties with arithmetic. The weak performances in arithmetics might point to
      some weaknesses in the neuropsychological domain. These results probably have
      complex explanatory causes and need to be further evaluated.

PMID- 15513582
TI  - The relationship between maternal smoking and breastfeeding duration after
      adjustment for maternal infant feeding intention.
AB  - AIM: To investigate whether maternal smoking remains associated with decreased
      breastfeeding duration after adjustment for the mother's infant feeding
      intention. METHOD: Pregnant women resident within Avon, UK, expected to give
      birth between 1 April 1991 and 31 December 1992 were recruited in a longitudinal
      cohort study. Main outcome measures included maternal infant feeding intention at
      32 wk of pregnancy: intention for the first week, intention for the rest of the
      first month and intention in months 2 to 4. Maternal smoking was defined as any
      smoking reported at any time during pregnancy. Data on initiation and duration of
      breastfeeding were based on the questionnaire at 6 mo postpartum, supplemented by
      data from the 15-mo questionnaire if necessary. RESULTS: Women who smoked during
      pregnancy had an adjusted odds ratio of 1.5 (95% CI: 1.3-1.7) of not
      breastfeeding at 6 mo compared to non-smokers (adjusting for maternal age,
      education and intention). Survival analysis of duration of breastfeeding in the
      first 6 mo postpartum found that women who intended to breastfeed for less than 1
      mo were 78% more likely to stop at any given time than women planning to
      breastfeed for at least 4 mo, while smokers were 17% more likely to stop
      breastfeeding than non-smokers. CONCLUSION: Although women who smoke are less
      likely to breastfeed their infants than are non-smoking women, it appears that
      this is largely due to lower motivation to breastfeed rather than a physiological
      effect of smoking on their milk supply.

PMID- 15513583
TI  - Time trend of childhood type 1 diabetes incidence in Lithuania and Sweden, 1983
      2000.
AB  - AIM: To compare the time trend of childhood type 1 diabetes over an 18-y period
      in Lithuania and Sweden--countries with different incidence levels and different
      socio-economic conditions. METHODS: Percent average incidence change per year
      between 1983 and 2000, based on 8031 Swedish and 1100 Lithuanian cases in the age
      group 0-14 y, was calculated using Poisson regression. RESULTS: Average age- and
      sex-standardized incidence/100 000/y was 28.9 (95% CI: 28.2-29.5) in Sweden and
      7.5 (95% CI: 7.1-8.0) in Lithuania. Between 1983 and 2000, the average increase
      per year was 2.2% in Sweden (95% CI: 1.7-2.6) and 2.3% in Lithuania (95% CI: 1.1
      3.5), but the latter trend depended on an increase during the last few years of
      the period, and only for girls. In Sweden, incidence increased significantly in
      all age groups, but more so in the younger groups (3.0%, 2.2% and 1.7% per year
      in 0-4, 5-9 and 10-14-y age groups, respectively), while in Lithuania a
      significant increase was found only in the 10-14-y age group (3.0%). In Sweden, a
      trend towards a younger age at diagnosis was indicated for both boys and girls
      when comparing 1983-1991 and 1992-2000, whereas in Lithuania, the changes in age
      distribution over time were small, with an opposite tendency for boys.
      CONCLUSION: Incidence variability over time differed considerably in the two
      countries in the region of the Baltic Sea, suggesting a complex effect of
      environmental risk factors, some of which may be associated with wealth and socio
      economic conditions.

PMID- 15513584
TI  - Parent-completed developmental screening in a Norwegian population sample: a
      comparison with US normative data.
AB  - AIM: To compare normative data of a Norwegian translation of the Ages and Stages
      Questionnaires with original US normative data. METHODS: Norwegian-born mothers
      randomly selected from the population register completed Norwegian translations
      of the Ages and Stages Questionnaires, a series of 19 age-specific child
      development screening questionnaires each made up of 30 items in five domains:
      Communication, Gross Motor, Fine Motor, Problem Solving, and Personal-Social.
      Domain score group differences with original US normative data on 10 age-specific
      questionnaires (for ages 4, 8, 12, 16, 20, 24, 30, 36, 48, and 60 mo) were
      investigated. The Norwegian data consisted of 1341 children, varying between 82
      and 176 per age interval. RESULTS: On the whole, parents' reports of their
      children's development were very similar in the two data sets. Only five out of
      50 mean comparisons revealed a mean difference either greater than a Cohen's d of
      0.5 or greater than the smallest increment on a domain score. The variation in
      scores tended to be somewhat smaller in the Norwegian sample. CONCLUSION: It
      seems reasonable to expect that domain scores on the Ages and Stages
      Questionnaires may be interpreted in the same way in Norway and the United
      States, and these results may also generalize to other Western settings. These
      findings from a true random sample also increase the confidence in the original
      normative data.

PMID- 15513585
TI  - Knowledge of and attitude towards circumcision of adult Korean males by age.
AB  - AIM: Circumcision is widely practised in Korea, but little is known regarding the
      public's attitude towards circumcision. This study was designed to evaluate the
      knowledge and the general opinion of Korean adult males towards circumcision.
      METHODS: Fifteen hundred self-completion questionnaires were distributed to adult
      males in five decadal age groups ranging from 10 to 59 y old. Questions
      concerning opinions regarding the necessity, reasons, potential benefits and
      disadvantages of circumcision, as well as the role of peer pressure upon the
      decision to circumcise were included. Completed questionnaires were collected and
      analysed statistically. RESULTS: The achieved response rate was 62.7%. 73.1%
      believed that circumcision is necessary, while 7.1% believed it is not necessary.
      The principal reason for circumcision was to improve penile hygiene (77.9%).
      68.7% did not prefer neonatal circumcision regardless of the respondent's age.
      The major reason was fear of pain (36.9%). Peer pressure was one of the most
      influential factors when deciding upon circumcision: 60.8% believed that they
      might be ridiculed by their peer group unless circumcised, and the younger the
      age of the respondent, the more frequently this opinion was held (p < 0.05).
      62.7% thought that circumcision would prevent genital tract infection of the
      sexual partner. Respondents with older age tended to emphasize improved sexual
      potency (p < 0.05). CONCLUSIONS: This study indicates that common beliefs of
      adult males about circumcision in Korea are relatively homogeneous. Tailored
      education about circumcision is needed.

PMID- 15513586
TI  - Migrant children--a challenge for European paediatricians.
AB  - Each year, tens of thousands of children seek asylum in Europe. Irregular
      immigration, family reunification programmes and labour migrants contribute
      additional large populations to the migrant scene in Europe. Paediatricians
      struggle to find solutions to their needs of health and medical care within
      different societal and political contexts on a common platform of children's
      rights and medical ethics. CONCLUSIONS: Migrant children have important health
      and protection needs. Paediatricians can improve the health and well-being of
      migrant children by assuring access to paediatric healthcare regardless of the
      child's legal status. Paediatricians can play an important role in advocating for
      migrant children in their local community, through concerted activities of
      national paediatric societies, and through the international paediatric
      community. National paediatric societies need to put migrant children high on
      their agenda in discussions with policy and decision makers. Initiatives are
      needed to create platforms within the international paediatric community where
      practical strategies to the multitude of issues touched upon by migrant children
      can be exchanged and international advocacy organized.

PMID- 15513587
TI  - Continuous measurement of cerebral blood volume and oxygenation during rewarming
      of neonates.
AB  - AIM: To investigate the effect of rewarming in preterm infants presenting with
      hypothermia at admission. METHODS: The tissue oxygenation index (TOI), changes in
      cerebral blood volume (DeltaCBV) and changes in intravascular oxygenation
      (DeltaHbD) were measured in eight preterm infants, presenting with a temperature
      less than 35 degrees C at admission. RESULTS: A significant increase in HbD and
      TOI was seen in four patients (group A), while a significant increase in CBV and
      a decrease in HbD was seen in four other patients (group B). Retrospective
      analysis showed that group A had important signs of peripartal asphyxia.
      CONCLUSION: While infants with peripartal asphyxia showed an important increase
      in oxygenation during rewarming, no significant changes were seen in the non
      asphyxiated infants.

PMID- 15513588
TI  - Antipsychotic medication and marked hyperprolactinaemia: iatros or true
      prolactinoma?
AB  - AIM: To demonstrate that hyperprolactinaemia and/or prolactinoma occur in
      association with antipsychotic medication use. METHODS: Three case studies of
      patients with markedly elevated serum prolactin level (>132 microg/l); either
      antipsychotic medication induced or as a consequence of a prolactinoma.
      CONCLUSION: The management and investigation of children with markedly elevated
      serum prolactin levels remains poorly defined. In our case series, two patients
      were found to have prolactinomas. We suggest that paediatric patients with serum
      prolactin level above 50 microg/l in males and 70 microg/l in females, regardless
      of any antipsychotic medication use, receive magnetic resonance imaging to
      exclude prolactinoma.

PMID- 15513589
TI  - A case of Kawasaki disease associated with syndrome of inappropriate secretion of
      antidiuretic hormone.
AB  - Kawasaki disease (KD) is an acute vasculitis of unknown aetiology with varied
      clinical manifestations. Although coronary arteritis is common in the course of
      KD, central nervous system involvement is rare. We report a case of KD in an
      infant who developed convulsions and apnoea during his illness associated with
      syndrome of inappropriate secretion of antidiuretic hormone (SIADH). CONCLUSION:
      The possibility of severe hyponatraemia should be anticipated in children with
      KD. Infants with KD are at risk of SIADH and should be monitored closely for its
      development.

PMID- 15513590
TI  - Congenital rubella with bilateral cataract detected at 5 weeks.

PMID- 15513594
TI  - Prefabrication of bone by vascular induction: an experimental study in rabbits.
AB  - The various methods of prefabricating flaps include vascular induction through
      staged transfer; pretransfer delay, expansion, and grafting; the use of
      alloplastic materials; and tissue bioengineering. In this experimental study,
      vascular induction was used to provide an axial vascular pedicle to randomly
      nourished tissue. Twenty-six New Zealand rabbits, ages and weights ranging
      between 6 months-1 year and 1.5-3.5 kg, respectively, were used. The sex
      difference was not considered. The deep inferior epigastric artery and vein were
      used to carry blood and were placed into a segment of femur to prefabricate the
      bone. Four weeks later, the viability of the segment of bone prefabricated by new
      axial pedicle was shown by scintigraphic study, and the new axial pedicle was
      ready for free transfer.

PMID- 15513595
TI  - Anatomical study of subcutaneous adipofascial tissue: a concept of the protective
      adipofascial system (PAFS) and lubricant adipofascial system (LAFS).
AB  - The subcutaneous adipofascial tissue over the entire body was radiographically
      and macroscopically investigated in 20 fresh and embalmed cadavers. The
      subcutaneous adipofascial tissue was made up of two adipofascial layers. Because
      the superficial layer forms a solid structure and is thought to protect against
      external forces, the adipofascial system formed by the solid structure was named
      the "protective adipofascial system (PAFS)". Because the deep layer forms a
      mobile layer and is thought to lubricate musculoskeletal movement, the
      adipofascial system formed by the mobile structure was named "lubricant
      adipofascial system (LAFS)". By classifying subcutaneous adipofascial tissue by
      its functional characteristics, we found we could understand the subcutaneous
      adipofascial structure over the entire body well.

PMID- 15513596
TI  - Inadequate blood supply persists in keloids.
AB  - We have previously shown that the adenosine triphosphate (ATP) content of keloids
      remains high for a long time. In keloids, anaerobic glycolysis may be related to
      the production of ATP. In this study, we counted the vessels in keloids,
      hypertrophic and atrophic scars in a defined area, and measured the cross
      sectional areas of their internal lumens immunohistopathologically and the
      lactate concentrations. The mean number in a defined area was smallest in keloids
      as was the mean internal area of vessels. The lactate content of keloids was 39.4
      (13.5) mmol/g of protein, of red scars 23.8 (7.5), of pink scars 23.8 (7.6), and
      of white scars 13.3 (7.3). These results indicate that ATP may be produced by
      anaerobic glycolysis in keloids, and that the decreased and narrowed vessels may
      reduce oxygen perfusion. The blood supply to keloids is inadequate, and this
      persists.

PMID- 15513597
TI  - Facial reanimation by transplantation of a microneurovascular muscle: long-term
      follow-up.
AB  - The two-stage operation for reanimation of long-standing facial paralysis by
      cross-facial nerve grafting and later free microneurovascular muscle transfer has
      been the treatment of choice for nearly 25 years. However, the functional outcome
      may be unpredictable. We therefore need to know more about the factors that
      influence the final result. We have recorded the long-term results of
      microneurovascular surgery in facial paralysis, and evaluated which factors
      influenced the functional outcome. Twenty-seven of 40 patients aged 7 to 65 years
      (mean 40) operated on at Helsinki University Hospital between 1986 and 2000 were
      available for interview and video recording. The gracilis, latissimus dorsi, and
      serratus anterior muscles were used for microneurovascular transfer in 11, 10,
      and 6 cases, respectively. The outcome of microneurovascular muscle transfer was
      graded on House's scale 1 to 6. The mean follow-up period was 8.5 years (range 2
      to 15). Sixteen patients (59%) displayed only mild or moderate dysfunction
      (grades 2 to 3) after reconstruction. In 8 patients (30%) dysfunction was graded
      as moderately severe, and in 3 (11%) as severe. There was a correlation between
      final functional outcome and the follow-up time after microneurovascular facial
      reanimation. The longer the follow-up time after muscle transplantation the
      poorer the functional result (p = 0.003). Twenty-one patients (78%) considered
      that their quality of life was better or much better after facial reanimation.
      Patients' satisfaction correlated with a good functional result.

PMID- 15513598
TI  - Maxillary distraction in patients with cleft deformity using a rigid external
      distraction device: a pilot study on the distraction ratio of the maxilla to the
      device.
AB  - We examined the ratio between actual maxillary distraction and the distraction of
      the rigid external distraction device (Rigid external distraction (RED) system)
      used for maxillary distraction in patients with a cleft deformity. Twelve
      patients were examined. The amount of maxillary advancement was measured on
      lateral cephalograms and divided by the activation amount on the RED system. The
      value obtained was represented as the distraction ratio of the maxilla to the
      system. The mean ratio in 10 patients with complete cleft lip, palate, and
      alveolus (complete cleft) was 0.24. However, the ratios in two patients with
      cleft lip and alveolus or soft cleft palate (incomplete cleft) were considerably
      higher than the mean ratios in patients with complete cleft. When the maxilla is
      distracted in patients with complete cleft using the RED system, the amount of
      activation on the system needs to be about four times the amount of planned
      maxillary distraction. However, the distraction ratio may be affected by the type
      of cleft.

PMID- 15513599
TI  - Reconstruction of a defect after harvesting a radial forearm flap using a narrow
      pedicled paraumbilical perforator-based subdermal vascular network (super-thin)
      flap.
AB  - The radial forearm flap is one of the most reliable flaps, but it has serious
      cosmetic donor site morbidity. We therefore reconstruct the defect after
      harvesting a radial forearm flap using a narrow pedicled paraumbilical perforator
      based subdermal vascular network (super-thin) flap to overcome this problem.

PMID- 15513600
TI  - Reconstruction of soft tissue after complicated calcaneal fractures.
AB  - A total of 35 flap reconstructions were done to cover exposed calcaneal bones in
      31 patients. All patients had calcaneal fractures, 19 of which were primarily
      open. Soft tissue reconstruction for the closed fractures was indicated by a
      postoperative wound complication. A microvascular flap was used for
      reconstruction in 21 operations (gracilis, n = 11; anterolateral thigh, n = 5;
      rectus abdominis, n = 3; and latissimus dorsi, n = 2). A suralis neurocutaneous
      flap was used in eight, local muscle flaps in three, and local skin flaps in
      three cases. The mean follow-up time was 14 months (range 3 months-4 years). One
      suralis flap failed and was replaced by a latissimus dorsi flap. Necrosis of the
      edges that required revision affected three flaps. Deep infection developed in
      two patients and delayed wound healing in another four. During the follow-up the
      soft tissues healed in all patients and there were no signs of calcaneal
      osteitis. Flaps were considered too bulky in five patients. Soft tissues heal
      most rapidly with microvascular flaps. In the long term, gracilis muscle covered
      with free skin grafts gives a good contour to the foot. The suralis flap is
      reliable and gives a good final aesthetic outcome. Local muscles can be
      transposed for reconstruction in small defects.

PMID- 15513601
TI  - Surgical treatment of ulcers caused by extravasation of cytotoxic drugs.
AB  - Despite preventive measures, the extravasation of cytotoxic drugs still occurs in
      0.6% to 6% of cases. The aetiology is thought to be that tissue necrosis develops
      into a chronic ulcer, which causes problems if the harmful action of the drug is
      not blocked. From 1988-2002 at the Department of Plastic Surgery of Rome
      University "La Sapienza", 240 patients presented with extravasation of cytotoxic
      drugs; all had been treated with an original conservative protocol first
      described in 1994, based on the repeated local infiltration of a large quantity
      of saline solution (90-540 ml) into the area of extravasation. We considered only
      cases with actively necrotic lesions. Eleven of the 240 patients (5%) had ulcers
      ranging from small ulcers to extensive areas of tissue necrosis. Of the 11
      patients, eight had already had ulcers, while the remaining three were those in
      whom our conservative protocol had not prevented necrosis. They were all operated
      on and given grafts, local flaps, reverse radial flaps, and free flaps.

PMID- 15513602
TI  - Experience with the AO Pi-plate for displaced intra-articular fractures of the
      distal radius.
AB  - We have used open reduction and internal fixation (ORIF) with the AO pi-plate in
      32 displaced, intra-articular fractures of the distal radius. The indication was
      a displaced intra-articular fracture with a step-off of more than 1 mm and a gap
      between fragments of more than 3 mm, judged from the primary computed tomograms
      (CT). All fractures were classified as AO type C3. Twenty-nine patients were
      followed-up after a mean of 23 (9-46) months. The dorsal tilt, the radial length,
      the radial inclination, the articular step-off, and the intra-articular gap
      between fragments were substantially improved postoperatively. All the patients
      had excellent or good extra-articular and intra-articular alignment. Two patients
      had reduced extension power of the first finger. Seventeen patients had
      Disability of the arm, shoulder, and hand (DASH) scores of less than 10 points,
      five had scores between 11 and 20, three between 21 and 30, three between 31 and
      40, and one patient had a score of 65 points. Complications occurred in two
      patients: one had a painful amputation neuroma of the superficial radial nerve,
      and one developed adhesions of the flexor tendons of the second and third fingers
      because the screws were too long and had penetrated the tendon sheaths. We
      conclude that the AO pi-plate is an excellent option for the most comminuted
      fractures of the distal radius.

PMID- 15513603
TI  - Injuries to children's hands caused by the engine belts of agricultural machines:
      classification and treatment.
AB  - Injuries to children's hands with farm machinery, particularly tractors, are
      common in rural areas. We present 58 cases of hand injuries in children aged from
      3 to 7 (mean 4.5), caused by the engine belts of agricultural vehicles, who were
      referred from the cities in Central Anatolia. The injury patterns among patients
      were similar. The injury generally starts from the middle phalanx of the third
      finger, crosses the proximal phalanx of the fourth finger and ends in the
      hypothenar region. The patients were categorised into five groups and treatment
      planned accordingly. The most commonly involved digit was the third finger and
      the thumb the least. Surgical treatment depended on the severity of the injury
      and included primary closure of the lacerations, tendon repair, fixation of
      fractures, grafting, and local flaps. Results of these injuries are generally
      poor, so prevention is more important.

PMID- 15513604
TI  - Use of a combined pedicled toe fillet flap.
AB  - We report the use of a double toe fillet flap combined with reconstruction of the
      joint capsule of the metatarsal proximal phalanx (MP) in a diabetic patient with
      a chronic persistent deep plantar ulcer and an avulsed third MP joint. Not only
      was the soft tissue defect dealt with, but also the stability of the MP joint was
      increased by the vascularised extensor tendon provided by the pedicled toe fillet
      flap.

PMID- 15513605
TI  - Resurfacing of the donor defect with a second toe plantar flag flap after free
      first toe pulp flap.
AB  - A second toe plantar flap was attached to the donor site after a free first toe
      pulp flap. Twenty-two days postoperatively, the wound had almost healed. Although
      the whole defect is impossible to cover with this flap, partial resurfacing will
      reduce the healing time and morbidity from recurrent ulceration.

PMID- 15513606
TI  - Accessory extensor pollicis longus.
AB  - Phylogenetically the accessory extensor pollicis longus in man seems to find its
      origin in the deep extensor layer, and this has largely been described in
      primates. I describe a case and present a comprehensive review of other
      publications on the subject.

PMID- 15513607
TI  - Fibroma of a tendon sheath at the wrist: a rare cause of compression of the
      median nerve.
AB  - We report a case of fibroma of a tendon sheath, a rare benign tumour, which
      presented as a painless swelling at the wrist and caused symptoms of median nerve
      compression. We have also reviewed similar cases.

PMID- 15513608
TI  - Osseous destruction and rupture of the extensor tendon caused by sarcoidosis of
      the finger.
AB  - We describe a woman with osseous destruction and rupture of the extensor tendon
      as a result of sarcoidosis in the left third finger with no evidence of systemic
      involvement. The tendon was repaired and she was successfully treated with
      prednisone.

PMID- 15513610
TI  - Post-traumatic stress disorder: the chameleon of psychiatry.
AB  - Post-traumatic stress disorder (PTSD) has been included in the DSM category of
      psychiatric diagnoses since 1980, classified as an anxiety disorder. Since that
      time, its definition has undergone considerable change and today many physicians
      are not aware of its current diagnostic criteria or the clinical significance of
      its high degree of comorbidity with other psychiatric and somatic conditions.
      PTSD can appear in different forms, and its many manifestations often identified
      and dealt with, while the underlying pathological trauma and psychological damage
      continues unrecognized and untreated, resulting in negative consequences for the
      patient and society. The extent of the problem is considerable in North America
      but prevalence studies in Europe are practically non-existent amongst the general
      population, with the subsequent result being that the degree and severity of the
      problem in Europe remains unknown. This article briefly looks at the history and
      metamorphosis of PTSD and discusses its present niche in relation to primary
      healthcare.

PMID- 15513611
TI  - Traumatic experiences and dissociative symptoms among Swedish adolescents. A
      pilot study using Dis-Q-Sweden.
AB  - The aim of this study was to explore the occurrence of dissociative symptoms in
      relation to reported traumatic experiences among adolescents. A normative sample
      of 216 adolescents and a clinical sample of 30 cases with a history of
      traumatization were given the Swedish translation of Dissociation Questionnaire,
      DIS-Q. The results showed that 8.8% of the adolescents reported scores above the
      cut-off score of 2.5 on the Dis-Q-Sweden, with a female-male ratio of 2.6:1. In
      the normative sample, 53 (24.5%) of the adolescents reported one or more trauma
      experiences. The adolescents who self-reported trauma experiences in the
      normative sample scored higher on the total Dis-Q-Sweden scores and on three of
      the four subscales compared to the adolescents with no such experiences. The
      clinical group exhibited significantly higher Dis-Q-Sweden scores than the
      normative sample on every scale, with 60% above the cut-off score. The study
      confirms the results from earlier studies that adolescents with a history of
      trauma exhibit more dissociative symptoms in this study according to Dis-Q
      Sweden. The impact of trauma qualities and background factors on the development
      of dissociative symptoms need to be studied further.

PMID- 15513612
TI  - Comparison of hospital-treated personality disorders and personality disorders in
      a general population sample.
AB  - The distribution of personality disorders (PDs) was explored in hospital-treated
      subjects and in a population subsample. This study forms a part of the Northern
      Finland 1966 Birth Cohort study. Hospital case records of psychiatric treatment
      periods of all cohort members (n=11,017) were reviewed and re-checked against DSM
      III-R criteria. A subsample of the cohort members living in Oulu (n=1609) were
      invited to a two-stage psychiatric field survey with Structured Clinical
      Interview for DSM-III-R (SCID) as a diagnostic method. The most common PDs in
      hospital-treated sample were cluster B PDs (erratic). In the population
      subsample, cluster C PDs (anxious) formed the majority.

PMID- 15513613
TI  - Violence and threats of violence within psychiatric care--a comparison of staff
      and patient experience of the same incident.
AB  - This study compared staff members' and psychotic patients' experiences of one and
      the same violent incident. The staff exposed to the violence completed the Staff
      Observation Aggression Scale (SOAS). The patients who had exhibited the violent
      behaviour were interviewed prior to discharge from the ward. When comparing the
      SOAS data with the patient interviews, it was found that the staff members were
      able to identify less than 50% of the provocations that the patient experienced.
      According to the patient interviews, giving the patient medication was far more
      often experienced as a provocation, resulting in violence, than the staff
      perceived. Knowledge about how to interpret the patients' body language and other
      signals, and how patients perceive the staff's behaviour, must be understood for
      an efficient prevention of violence in psychiatric care.

PMID- 15513614
TI  - The prevalence of dyslexia and AD/HD in a sample of forensic psychiatric rapists.
AB  - The prevalence of dyslexia and attention deficit/hyperactivity disorder (AD/HD)
      (DSM-IV) is markedly increased among those who are sentenced for criminal
      offences. The aim of the study was to identify developmental disabilities,
      dyslexia and AD/HD among severely disturbed men in forensic psychiatric care, and
      to study the co-occurrence of such disabilities, with the objective to discuss
      the importance of the diagnoses in forensic psychiatry. The participants were 10
      males who had committed rape on adult women, and included two murder-rapists, one
      of which had murdered more than one victim (i.e. a serial murderer). All had been
      assigned to special long-term forensic psychiatric care, based predominantly on a
      psychodynamic ground. In order to be identified as having dyslexia, a
      participant's performance on at least three out of four tests of academic skills
      had to be markedly below the expected level (more than two stanine steps), given
      the participant's non-verbal intellectual capacity and considering the length of
      his education. AD/HD was investigated by studying the participants' forensic
      psychiatric files and by a clinical interview. Seven of the 10 participants met
      the DSM-IV criteria for dyslexia, and six of them met the DSM-IV criteria for
      AD/HD. Four participants had AD/HD and dyslexia, three had AD/HD but no dyslexia,
      and two had dyslexia but no AD/HD. Only one participant had neither dyslexia nor
      AD/HD. The participants with dyslexia performed well in tests assessing non
      verbal reasoning, visuo-spatial capacity and visual memory. Although the
      generalization of the results from 10 rapists is severely limited, the results
      indicate the importance of assessing dyslexia as well as AD/HD in people who are
      admitted for forensic psychiatric assessment. The lack of correct diagnoses may
      negatively influence the choice of appropriate forensic psychiatric care. Early
      assessment of those disorders might have a positive influence on the
      psychological development and socialization process in people with dyslexia
      and/or AD/HD.

PMID- 15513615
TI  - Changes in mental well-being during Minnesota treatment.
AB  - The present study assessed mental well-being daily in 28 alcohol-dependent
      patients who underwent 28 days of Minnesota inpatient treatment. The Swedish Mood
      Adjective Check List (sMACL) with six bipolar dimensions was used for daily self
      reports. At start of treatment, patients had lower levels in four dimensions of
      mental well-being compared to those of a norm group. Moreover, patients showed
      significant improvements in all levels of mental well-being during treatment, and
      at the end of treatment patients had values within the normal range, except for
      one dimension (activation/deactivation), in which the levels were significantly
      higher. The findings may suggest a beneficial effect of this type of treatment on
      mental well-being, although findings may also reflect a mere effect of adjustment
      to treatment or the social situation.

PMID- 15513616
TI  - Suicide-preventive activities in psychiatric care: evaluation of an educational
      programme in suicide prevention.
AB  - To promote implementation of suicide-preventive activities, the Swedish National
      Centre for Suicide Research and Prevention of Mental Ill-Health (NASP) introduced
      a 200-h academic, postgraduate educational programme (based on the training-of
      trainers model) in suicide prevention. This programme was provided at Karolinska
      Institute, Stockholm, for key persons in psychiatric care. Twenty-nine key
      persons from 11 psychiatric intervention clinics in Stockholm County attended the
      first course. Preconditions for implementing suicide-preventive activities were
      assessed by means of semi-structured interviews with all course participants
      still working in the intervention clinics (n=10). In all but one of these 10
      clinics, a wide range of suicide-preventive activities had been implemented as a
      result of the NASP course. Activities varied in scope, but the key persons seemed
      to have succeeded in pinpointing the key elements in suicide prevention - the
      need for specific knowledge about the suicidal process and for well-defined
      suicide-preventive routines. However, organizational factors and staff turnover
      were obstacles to maintaining and making the activities routine. There is a need
      to strengthen the course participants' formal roles as implementers and encourage
      the clinical management in their continuous implementation of suicide-preventive
      activities.

PMID- 15513617
TI  - The influence of childhood sexual abuse factors on women's health.
AB  - A history of childhood sexual abuse has been shown to be common among adult
      women, 15-30% in prevalence studies. The childhood sexual abuse variables taken
      into account are commonly age of onset, duration, abuse forms and relationship
      between the child and the perpetrator. Within the Department of Psychiatry at
      Lund University Hospital, 45 women with experiences of childhood sexual abuse
      were offered a 2-year long trauma-focused group therapy. Half of the women had
      been sexually abused during childhood in pre-school ages and half by a
      perpetrator who was the biological father. Two-thirds had been abused for more
      than 5 years and half through penetration. There was a statistical significance
      between age of onset (0-6 years) and psychiatric symptoms including eight of nine
      subscales, according to results from use of the questionnaire Symptom Check List
      (SCL-90). According to the same questionnaire, there also was a statistical
      significance between the perpetrator (male relative) and the subscale
      interpersonal sensitivity. According to the Interview Schedule of Social
      Interaction, there was a statistical significance between the abuse form
      penetration and the social integration in the subscale availability of
      attachment. Thirty-five women (78%) had not told anyone about the sexual abuse
      when it happened, and the most common reason for this was fear of not being
      believed.

PMID- 15513618
TI  - Psychiatric occupational therapy service--quality assurance.
AB  - During the last few decades, quality assurance has been a central issue in the
      societies, both in, for example the industrial area and in healthcare. It is a
      tool to measure the outcomes of product or service provided. A review of the
      literature during the last 17 years with respect to quality assurance work in
      psychiatric occupational therapy indicates that few articles have been published
      in the area and that their scientific quality is questionable. The studies show
      many methodological shortcomings, which result in difficulty drawing any
      conclusion from the studies. The number of publications is also decreasing.
      Furthermore, a survey to investigate quality assurance work in psychiatric
      occupational therapy service shows that the occupational therapists do not work
      with quality assurance methods to a great extent. The methods they use most are
      interviews with patients and patient questionnaire. Both these methods require
      documentation in order to offer the patient a suitable service. Quality assurance
      work will be difficult to implement if no documentation is available.
      Documentation is central to communicating with other professions and with the
      client. This study points out that occupational therapists need to improve
      practice as well as research concerning quality assurance in order to ensure that
      they offer the patient a high-quality service.

PMID- 15513647
TI  - Sickness absence: causes, consequences, and physicians' sickness certification
      practice. A systematic literature review by the Swedish Council on Technology
      Assessment in Health Care (SBU).

PMID- 15513650
TI  - Swedish Council on Technology Assessment in Health Care (SBU). Chapter 1. Aim,
      background, key concepts, regulations, and current statistics.

PMID- 15513651
TI  - Swedish Council on Technology Assessment in Health Care (SBU). Chapter 2. Methods
      used for the systematic literature search and for the review of relevance,
      quality, and evidence of studies.
AB  - Published scientific studies on the topics of sick leave, disability pension, and
      sick-listing practices were searched for, reviewed, and compiled for this report.
      The approach used reflects in many ways the criteria for systematic literature
      reviews in health care often associated with the Cochrane Collaboration. The area
      addressed by the literature review - sick leave - requires, however, some
      specific review criteria (see below).

PMID- 15513652
TI  - Swedish Council on Technology Assessment in Health Care (SBU). Chapter 3. Causes
      of sickness absence: research approaches and explanatory models.
AB  - Research on sickness absence, emanating from different theoretical perspectives
      and questions, is carried out within several different scientific disciplines.
      Studies are often based on explanatory models addressing the causes of sickness
      absence. Here, a brief summary of the various approaches and explanatory models
      used in sickness-absence research is presented. Also explanatory models for
      changes over time in sickness absence are briefly discussed.

PMID- 15513653
TI  - Swedish Council on Technology Assessment in Health Care (SBU). Chapter 4.
      Methodological aspects in sickness-absence research.
AB  - Several methodological aspects concerning research on sickness absence and
      disability pension are noteworthy, including: empirical research is being
      conducted within many different disciplines using various study designs; progress
      in theory development has been slow and weak; several outcome measures are used;
      terminology varies widely; and comparative research is difficult to conduct since
      insurance systems differ over time and among nations and employers.

PMID- 15513654
TI  - Swedish Council on Technology Assessment in Health Care (SBU). Chapter 5. Risk
      factors for sick leave - general studies.
AB  - Extensive information is available from official statistics and descriptive
      studies on the association between different socio-demographic background factors
      and sickness absence. This information addresses age, gender, place of residence,
      and socio-economic status. However, few studies have thoroughly analysed these
      background factors, and rigorous scientific evidence on the causal relationship
      between these factors and sick leave is lacking. Regarding the family, we found
      no scientific evidence that marital status or children living at home were
      associated with sickness absence. However, we found limited scientific evidence
      for an effect of divorce. Regarding work-related factors, we found limited
      scientific evidence for an effect of physically stressful work, and moderate
      scientific evidence for low psychological control over the work situation. We
      found limited scientific evidence for a correlation in time between unemployment
      and sickness absence, but insufficient scientific evidence for the causes of the
      association. There was moderate scientific evidence that the amount of sickness
      absence is influenced by the design of the social insurance system, but
      insufficient evidence on the magnitude of change required to influence the level
      of sickness absence. Essentially the same results apply to disability pension,
      although the number of studies is small. However, we found moderate scientific
      evidence for the effects of socio-economic status, which could be explained
      partly by childhood experiences.

PMID- 15513655
TI  - Swedish Council on Technology Assessment in Health Care (SBU). Chapter 6.
      Sickness absence due to back and neck disorders.
AB  - The scientific evidence on the causes for sick leave attributed to back and neck
      disorders was reviewed. Categories were established for acute, recurring, and
      chronic problems based on the duration of the sick leave period. Forty-eight
      articles were found to be relevant, whereof two were of high quality and 26 were
      of medium or low quality. Quality was assessed exclusively in relation to the aim
      of this systematic review. The results reveal limited published research on
      causes for sick leave from back and neck disorders. The generalisability of the
      findings is also limited since most of the subjects were men and employees in
      manufacturing industries. Women, white-collar workers, employees in the public
      sector (care, social services, schools, etc) were underrepresented in the
      studies. Hence, these groups and areas should be studied further to verify
      conclusions and enhance knowledge about the causes for sick leave from back and
      neck disorders. The following factors were found to have consistent, but limited,
      support as regards their influence on the risk for sick leave due to back and
      neck disorders: (a) heavy physical workload, bent or twisted working position,
      and low work satisfaction increases the risk for short-term and long-term sick
      leave; (b) specific back diagnoses and previous sick leave due to back disorders
      increases the risk for short-term and long-term sick leave; (c) female gender,
      smoking, exposure to vibration, and deficient social support were not found to
      significantly increase the risk for short-term and long-term sick leave; (d) self
      reported pain and functional impairments were associated with a high risk for
      long-term sick leave; (e) longer employment periods reduced the risk for short
      term sick leave; (f) perceived demands at work did not influence short-term sick
      leave; (g) female gender and higher age increases the risk for disability
      pension.

PMID- 15513656
TI  - Swedish Council on Technology Assessment in Health Care (SBU). Chapter 7.
      Sickness absence and psychiatric disorders.
AB  - There is limited scientific evidence that women have a higher frequency and
      incidence of sickness absence due to psychiatric diagnoses. Because of
      conflicting findings, there is insufficient evidence on gender differences in the
      duration of sickness absence. Because of conflicting findings, there is also
      insufficient evidence on the association between age and sickness absence with
      psychiatric diagnoses. There is insufficient evidence on the association of
      sickness absence due to psychiatric diagnoses with work-related factors, factors
      related to family and social networks outside of the job, and psychosocial
      factors in childhood and adolescence since none of the individual factors were
      investigated in more than a single study. The results were conflicting
      (insufficient evidence) in five studies that investigated whether individuals
      with psychiatric disorders were at greater risk for sickness absence and
      disability pension, irrespective of the diagnosis on the sickness certificate.
      The four studies that used alcohol diagnoses to identify alcohol problems found
      increased sickness absence irrespective of the diagnosis on the certificate
      (expressed as more sick-leave days or an increased risk for prolonged sickness
      absence in individuals with alcohol problems). Furthermore, two of the studies
      found an increased risk for disability pension in women diagnosed with alcohol
      problems. There is insufficient evidence because of too few studies. The results
      are conflicting with regard to the association between high alcohol consumption
      and sickness absence, irrespective of the diagnosis on the certificate
      (insufficient evidence).

PMID- 15513657
TI  - Swedish Council on Technology Assessment in Health Care (SBU). Chapter 8. Sick
      leave due to coronary artery disease or stroke.
AB  - The assessment of the literature on sick-leave with cardiovascular diseases
      include only studies with sufficient scientific quality. These studies describe
      sick leave following stroke, myocardial infarction, coronary artery bypass
      grafting (CABG), or percutaneous coronary intervention (PCI). We found limited
      scientific evidence for the following results: After stroke, more than half of
      the patients of working age returned to work (RTW) during the first year
      following onset (higher rate for the younger patients). The consequences of brain
      damage, e.g. impaired ADL ability or cognitive capacity, play an important role
      in this respect. Also after myocardial infarction most patients RTW. PCI is a
      milder coronary artery intervention than CABG and RTW is more rapid. However, in
      the long run there are no differences in sick leave. People at higher ages or
      with physically demanding jobs return to work to a lesser degree. An
      international comparison shows that the duration of sick leave due to these
      conditions in Sweden is longer than in other countries although there is no
      scientific evidence to support this practice. It appears that the interest in
      research on sick leave in patients with cardiovascular diseases has waned in
      recent years. Developments in acute cardiological care should inspire renewed
      scientific involvement in this area of research.

PMID- 15513658
TI  - Swedish Council on Technology Assessment in Health Care (SBU). Chapter 9.
      Consequences of being on sick leave.
AB  - The possible consequences of sick leave can be measured at different levels in
      society. This chapter focuses on the consequences from the perspective of the
      sick-listed individual. Sick leave may have both positive and negative
      consequences for the individual, e.g. regarding disease, health, working life,
      social life, lifestyle, and emotional aspects. Some of these factors have been
      investigated in different studies. However, scientific evidence is insufficient
      since there are too few studies on the consequences of sickness absence and
      disability pension. The lack of relevant studies is the most striking observation
      from the review of studies on the consequences of being sick listed.

PMID- 15513659
TI  - Swedish Council on Technology Assessment in Health Care (SBU). Chapter 10.
      Sickness presence.
AB  - The term "sickness presence" is used to describe situations where the ability to
      work is impaired due to disease, but yet the person goes to work. A problem is
      that the term "sickness presence" implies that being present at work is something
      exceptional if a person is sick. Most people diagnosed with a disease or disorder
      do, however, go to work and are not sick listed. Furthermore, the term "sickness
      presence" is rather diffuse, and it would be beneficial if one or several more
      specific terms could be used. The current body of scientific literature does not
      provide sufficient evidence to draw conclusions on the consequences of sickness
      presence.

PMID- 15513660
TI  - Swedish Council on Technology Assessment in Health Care (SBU). Chapter 11.
      Physicians' sick-listing practices.
AB  - Physicians' sick-listing practices have been studied to a very limited extent.
      There is limited scientific evidence that physicians perceive sick-listing duties
      to be difficult and problematic, regarding both the medical and the insurance
      related aspects. There is limited scientific evidence also that quality is often
      deficient in the sickness certificates issued by physicians. This may affect case
      management at the local insurance office. There is insufficient scientific
      evidence to explain the differences in physicians' sick-listing patterns. The
      effects on patients are also insufficiently studied.

PMID- 15513661
TI  - Swedish Council on Technology Assessment in Health Care (SBU). Chapter 12. Future
      need for research.
AB  - Despite the extensive consequences of sickness absence, scientific research is
      both surprisingly scarce and theoretically and conceptually underdeveloped. There
      are few longitudinal studies, and even fewer intervention studies. The medical
      aspects in sickness insurance are seldom addressed, effects of factors at
      different structural levels are not considered,and the consequences of sick leave
      have barely been studied. Furthermore, little is known about the employer's role
      and the layperson's perspectives. Gender and ethnicity factors should be
      considered further. The concept of work ability needs to be defined,
      problematized, and operationalized. However, it is not only more, but mainly it
      is studies of better quality that are needed, e.g. longitudinal studies,
      international comparative studies, and randomised controlled trials. This would
      require multidisciplinary research groups, long-term research environments,
      international commitment, opportunities for good professional development within
      the field, and reliable basic data, including sick-listing diagnoses.

PMID- 15513663
TI  - More and better research needed on sickness absence.

PMID- 15513664
TI  - A Swedish cost-effectiveness analysis of community-based Chlamydia trachomatis
      PCR testing of postal urine specimens obtained at home.
AB  - AIMS: A study was undertaken to assess the cost-effectiveness of identifying and
      treating asymptomatic carriers of Chlamydia trachomatis when using community
      based testing of urine specimens obtained at home and mailed to a central
      laboratory. METHODS: A total of 100 males and 100 females aged 20-24 living in
      Umea were randomly sampled from the population registry. A societal cost
      effective analysis was carried out, based on screening and medical care costs in
      Sweden. RESULTS: With a participation rate of 55% (45% males and 65% females),
      the female screening became cost-saving as the C. trachomatis prevalence exceeded
      5.1%, and the male screening became cost-saving with over 12.3% prevalence.
      CONCLUSION: Postal screening for C. trachomatis in an asymptomatic young
      population can be cost-effective only at prevalences higher than at present.

PMID- 15513665
TI  - Is calcaneal stiffness more sensitive to physical activity than forearm bone
      mineral density? A population-based study of persons aged 20-79 years.
AB  - AIMS: The aim of this study was to investigate the associations between forearm
      bone mineral density (BMD), calcaneal stiffness, and physical activity levels in
      a normal population using different non-invasive methods. METHODS: The
      participants were invited to undergo bone measurements using single photon
      absorptiometry of the forearm and quantitative ultrasound (QUS) of the calcaneal
      bone, and also to complete a questionnaire. Physical activity levels were
      designated low, moderate, and high in the question on leisure-time activity.
      RESULTS: There were 956 participants included in the present study. Forearm BMD
      in the eighth age decade was 0.40 g/cm2 (95% CI 0.33-0.46 g/cm2) lower than in
      the third decade among women and 0.28 g/cm2 (95% CI 0.18-0.37 g/cm2) lower among
      men. The differences in calcaneal stiffness between the same age decades were
      22.4 (95% CI 17.5-27.4) among women and 15.8 (95% CI 8.0-23.5) among men. The
      correlation between forearm BMD and calcaneal stiffness was 0.58 (95% CI 0.52
      0.64) in women and 0.34 (95% CI 0.25-0.42) in men. Reported moderate and high
      leisure-time activity levels in both genders were associated with higher
      calcaneal stiffness but not with forearm BMD. CONCLUSIONS: The QUS may be used to
      measure the effect of present physical activity levels on calcaneal bone at the
      population level. Further longitudinal studies are warranted in order to
      determine the most appropriate non-invasive method in population-based studies.

PMID- 15513666
TI  - Variations in the risk of disability pension in Norway 1970-99. A gender-specific
      age-period-cohort analysis.
AB  - AIMS: A study was undertaken to investigate whether cohort or period effects
      could explain the varying and generally increasing incidence of disability
      pension in Norway between 1970 and 1999. METHODS: The study used data from a
      complete national register of new disability cases in Norway, including all cases
      of disability pension in the 16-60 age group categorized according to age and
      gender for each year from 1970 to 1999. The population at risk was defined for
      each year from census data and number of individuals already receiving disability
      pension. Data were organized in five-year age groups, five-year time periods and
      corresponding overlapping nine-year birth cohorts. Age- and gender-specific rates
      were displayed graphically for periods and cohorts. Separate Poisson regression
      models were fitted for age periods and age cohorts. Finally a combined age,
      period, and cohort model was applied. RESULTS: The overall incidence was
      7.4/1,000 non-disabled persons per year for women and 6.0/1,000 for men. For
      women 52.1% of the cases were in the 51-60 age group, whereas the corresponding
      figure for men was 57.6%. Statistical analysis showed an increasing trend for
      both genders, more pronounced for women than men. All time periods deviated
      significantly from the trend, either upwards or downwards. Age-cohort models
      showed less variation, but recent cohorts had higher than expected rates,
      especially for men. CONCLUSIONS: Further studies should investigate why Norwegian
      women were more affected by the period effects than men. An increasing incidence
      of disability pension among recent cohorts is a major challenge for the Norwegian
      welfare system.

PMID- 15513667
TI  - Parasuicide in a low-income country: results from three-year hospital
      surveillance in Nicaragua.
AB  - AIMS: A study was undertaken to assess the incidence of parasuicide in Nicaragua,
      to identify groups at risk, and to describe the characteristics of parasuicides,
      such as methods used and seasonal and diurnal patterns. METHOD: All hospital
      admitted parasuicide cases in the area of Leon, Nicaragua, were assessed over a
      three-year period using standardized instruments. RESULTS: Two hundred and thirty
      three parasuicide cases were identified in the catchment area giving a
      parasuicide rate of 66.3/100,000 inhabitants per year based on the population 10
      years and older. Corresponding figure for 15 years and older was 71.3. A majority
      were females (68.8%), who were significantly younger than the males (mean 20.8
      years vs. mean 24.6 years). The highest rates were found in the age group 15-19
      years with a female rate three times higher than the male rate (302.9 vs. 98.9).
      Pesticides, a highly lethal substance, were used as method in 19.1% of the
      attempts. Consistent seasonal variation with peaks in May-June and September
      October were found over the years. Among parasuicide cases, 46.5% had been in
      contact with the healthcare system within 6 months before attempting suicide.
      CONCLUSIONS: Parasuicides represent a significant health problem among young
      people in Nicaragua. Preventive efforts should be directed especially towards the
      life situation for young girls, limitation of availability of suicide means,
      increased awareness in schools concerning suicidal problems, as well as improved
      management of patients with mental health problems within primary healthcare.

PMID- 15513668
TI  - Activities of daily living decrease similarly in hospital-treated patients with a
      hip fracture or a vertebral fracture: a one-year prospective study in 151
      patients.
AB  - AIMS: A hip fracture is commonly regarded as the most devastating fragility
      fracture, as regards both morbidity and mortality, while a vertebral fracture is
      usually regarded as having lower general morbidity. The purpose of this study was
      to investigate whether hospitalized patients with a hip or a vertebral fracture
      experience similar functional deterioration following the fracture as regards
      activity of daily living (ADL) and experienced quality of life (QOL). METHODS:
      Eighty-seven women and 22 men, mean age 81 (range 66-96), with a hip fracture and
      34 women and 8 men, mean age 81 (range 68-92), with a vertebral fracture were
      followed up for 12 months. ADL before fracture and at 4 and 12 months after the
      fracture were evaluated as well as QOL at 4 and 12 months after the fracture, by
      questionnaires. RESULTS: A hip and a vertebral fracture in community dwellers
      within the same age range confers a similar decrease in ADL during the four
      months following the fracture. No restoration was seen in ADL or total QOL during
      the year following the fracture. Patients with a vertebral fracture had a lower
      QOL than patients with a hip fracture 4 and 12 months after the fracture.
      CONCLUSION: The need for external community assistance for patients with a
      vertebral fracture that forces them to have hospital treatment may be similar to
      the need following a hip fracture.

PMID- 15513669
TI  - Adolescent alcohol use, psychological health, and social integration.
AB  - AIM: Alcohol use and intoxication are highly prevalent among adolescents and may
      be an important element of the socialization process in the teenage years.
      Significant short- and long-term health consequences seem evident. The aim of
      this study was to investigate the relationship between alcohol consumption and
      several aspects of psychological health and social integration in adolescents.
      METHODS: The study is based on data from a 1997 cross-sectional survey of 828
      Norwegian tertiary school students in Forde (91% of all students). Three hundred
      and eighty (46%) were female. The majority of students were aged 20 or younger,
      with 64% aged 15-17. Four groups were defined according to frequency of alcohol
      intoxication. Emotional health and social integration in the four groups are
      reported as means and the differences from the reference groups (with 95%
      confidence limits) were estimated. Control of confounding and interaction was
      performed. RESULTS: The study reveals that alcohol intoxication is an established
      element of mid-teenage behaviour for both sexes. It was found that depressive
      complaints and psychosomatic problems increased with increasing frequency of
      intoxication. Alcohol use is not only associated with improving friendship
      quantity but also with an improved quality of friendships. Heavy consumers report
      greater problems with relations with school and with their parents, especially in
      early adolescence. CONCLUSIONS: Though adolescents with moderate and heavy
      alcohol consumption are more sociable with friends, abstainers and light drinkers
      appear emotionally healthier. They succeed to a greater extent in a wide variety
      of social arenas, particularly in comparison with heavy consumers.

PMID- 15513670
TI  - Bridges, pathways and valleys: labour market position and risk of hospitalization
      in a Swedish sample aged 55-63.
AB  - BACKGROUND: The combination of population ageing and increasingly early labour
      market exit (LME) throughout Europe has made older age a key issue in social
      policy and research. There is increasing awareness that older people are a
      heterogeneous group in which health inequalities persist. However, the effects of
      different types of LME on health have received relatively little attention.
      Existing studies reach different conclusions. This might be due to several
      reasons: different types of LME are rarely explored in conjuncture; studies often
      lack objective assessments of health and frequently rely on small populations.
      This paper aims to test the relative effects of different LME on the risk of
      hospitalization compared with those who remained in paid employment. METHODS:
      Using Government register data on pooled cross-section samples of Swedish workers
      aged 55-63 years (n=7,024) the authors have compared the likelihood of
      hospitalization for three types of LME - disability pension (fortidpension),
      unemployment, and early retirement - with those who continue working. RESULTS:
      Controlling for previous hospitalization, sex, age, social class, and health at
      work a significant increased risk of hospitalization was found following LME for
      the unemployed (OR=1.98). CONCLUSION: Early LME is a varied process with mixed
      effects on health, and hence is of possible importance for policy, which,
      therefore, requires more attention. Programmes to help older unemployed workers
      back into work will have positive health effects for individuals and reduce
      welfare costs of hospitalization.

PMID- 15513671
TI  - Mortality from external causes in Lithuania: looking for critical points in time
      and place.
AB  - AIM: A study was undertaken to analyse trends in mortality from major external
      causes of death, and to detect urban/rural differences by cut points over the
      period of socioeconomic transition. METHODS: Information on deaths from major
      external causes (traffic accidents, suicides, and homicides) for the 1990-2000
      period was obtained from Lithuanian Department of Statistics. Mortality rates
      were age standardized, using the European standard, and analysed, according to
      (urban/rural) residence and sex. The Jointpoint analysis was used to identify the
      best-fitting points, wherever a statistically significant change in mortality
      occurred. RESULTS: The most critical point for external causes of mortality
      during the period of transition was the year 1994, when an increasing mortality
      trend reversed to a decreasing one. Mortality from suicides primarily caused
      these positive changes. Changes in mortality from traffic accidents were not
      significantly associated with the period under analysis. Numerous less favourable
      trends in rural areas, including suicide rates, traffic accidents, and homicides,
      are likely to stratify urban/rural health outcomes in the future. CONCLUSION:
      Despite a recent decline, mortality from external causes remains at an extremely
      high level in Lithuania. Future progress requires sustained improvements in
      prevention, and serious attention to external causes of death in health policy
      development.

PMID- 15513672
TI  - Social determinants for infant mortality in the Nordic countries, 1980-2001.
AB  - AIM: Social equity in health is an important goal of public health policies in
      the Nordic countries. Infant mortality is often used as an indicator of the
      health of societies, and has decreased substantially in the Nordic welfare states
      over the past 20 years. To identify social patterns in infant mortality in this
      context the authors set out to review the existing epidemiological literature on
      associations between social indicators and infant mortality in Denmark, Finland,
      Norway, and Sweden during the period 1980-2000. METHODS: Nordic epidemiological
      studies in the databases ISI Web of Science, PubMed, and OVID, published between
      1980 and 2000 focusing on social indicators of infant, neonatal, and postneonatal
      mortality, were identified. The selected keywords on social indicators were:
      education, income, occupation, social factors, socioeconomic status, social
      position, and social class. RESULTS: Social inequality in infant mortality was
      reported from Denmark, Finland, Norway, and Sweden, and it was found that these
      increased during the study period. Post-neonatal mortality showed a stronger
      association with social indicators than neonatal mortality. Some studies showed
      that neonatal mortality was associated with social indicators in a non-linear
      fashion, with high rates of mortality in both the lowest and highest social
      strata. The pattern differed, however, between countries with Finland and Sweden
      showing consistently less social inequalities than Denmark and Norway. While the
      increased inequality shown in most studies was an increase in relative risk, a
      single study from Denmark demonstrated an absolute increase in infant mortality
      among children born to less educated women. CONCLUSIONS: Social inequalities in
      infant mortality are observed in all four countries, irrespective of social
      indicators used in the studies. It is, however, difficult to draw inferences from
      the comparisons between countries, since different measures of social position
      and different inclusion criteria are used in the studies. Nordic collaborative
      analyses of social gradients in infant death are needed, taking advantage of the
      population-covering registers in longitudinal designs, to explore the mechanisms
      behind the social patterns in infant mortality.

PMID- 15513673
TI  - Indigenous health in the Arctic: an overview of the circumpolar Inuit population.
AB  - The health of the Inuit has undergone substantial changes over the past five
      centuries, as a result of social, cultural, and economic changes brought about by
      interactions with Europeans. This process was accelerated considerably in the
      second half of the twentieth century. The incidence of infectious diseases has
      declined considerably but is still high compared with Western societies. Chronic
      diseases such as diabetes and cardiovascular disease are on the increase, while
      accidents, suicides, violence, and substance abuse are of major importance for
      the pattern of ill health in most Inuit communities. Lifestyle changes, social
      change, and changes in society and the environment are major determinants of
      health among the Inuit.

PMID- 15513674
TI  - Humour seen from a public health perspective.
AB  - Humour is to be regarded as a salutogenic factor. As with other such factors
      there are reasons to believe that humour is a part of the individual's
      personality with the possibility of being strengthened by influences from the
      family, school, and workplace. The use of humour in population-based health
      promotive intervention strategies is a field lacking evidence-based knowledge.

PMID- 15513675
TI  - Accelerated atherosclerosis in inflammatory rheumatic diseases.
AB  - Over recent years it has become clear that patients with inflammatory rheumatic
      diseases are at increased risk of developing atherosclerosis. The exact causes
      for this are probably related in part to a general adverse effect of inflammation
      on atherogenesis, and in part to immune mechanisms specific to individual
      rheumatic diseases. This review discusses proposed mechanisms of accelerated
      atherosclerosis, including abnormal lipid and lipoprotein profiles, oxidative
      stress, enhanced apoptosis, thrombophilia, immune complexes, and increased
      mononuclear cell infiltration of atherosclerotic lesions, and local generation of
      cytokines.

PMID- 15513676
TI  - Risk assessment for coronary heart disease in rheumatoid arthritis and
      osteoarthritis.
AB  - BACKGROUND: The risk of coronary heart disease (CHD) is increased in rheumatoid
      arthritis (RA). The reasons for this remain unknown, but traditional risk factors
      for CHD identified in the general population may be important contributors.
      OBJECTIVE: To assess comparatively the prevalence of traditional CHD risk factors
      and the absolute 10-year CHD risk in patients with RA or osteoarthritis (OA)
      without known cardiovascular co-morbidity. METHODS: Consecutive Caucasian
      hospital outpatients with RA (n = 150) or OA (n = 100) aged 40-75 years were
      assessed for known cardiovascular co-morbidity, age, sex, smoking status,
      presence of diabetes mellitus (DM), height, weight, systolic blood pressure (BP),
      total cholesterol (TC) and HDL cholesterol. Absolute 10-year CHD risk for each
      individual was calculated using the Joint British Societies CHD risk calculator.
      RESULTS: Prevalence and distribution of known cardiovascular co-morbid conditions
      were similar in RA (56/150, 37%) and OA (34/100, 34%). The resulting subgroups of
      patients without known co-morbidity (RA: n = 94; OA: n = 66) were not
      significantly different for age, sex, DM, smoking, systolic BP or TC: HDL
      cholesterol ratio. There was no significant difference in the absolute 10-year
      CHD risk between RA and OA (15.6+/-11.0 versus 14.8+/-9.3, p = 0.63). However, a
      significant proportion of patients without known cardiovascular disease in both
      the RA and OA subgroups had a 10-year CHD risk above the 15% or 30% risk levels,
      indicating the need for possible or definite intervention respectively. Over 80%
      of RA patients had at least 1 CHD risk factor that could be modified. CONCLUSION:
      Absolute 10-year CHD risk was not different between RA and OA patients in this
      study. Substantial numbers of RA and OA patients have potentially modifiable CHD
      risk factors present. We suggest that CHD risk should be assessed and modifiable
      risk factors addressed in the routine rheumatology clinic setting.

PMID- 15513677
TI  - Aetiological factors of importance for the development of rheumatoid arthritis.
AB  - OBJECTIVE: To evaluate exposure to external factors associated with risk or
      prevention of rheumatoid arthritis (RA). METHODS: Two hundred and ninety-three
      incident cases of RA and 1346 population-based referents were included in a case
      referent study, in which previous exposure experiences were collected through a
      postal questionnaire. RESULTS: An inverse association between RA and additional
      schooling after compulsory school was seen for men. Current smoking was
      associated with significantly increased risks of RA for men and women [odds ratio
      (OR) 2.9, 95% confidence interval (CI) 1.4-6.4, and OR 1.8, 95% CI 1.1-2.9,
      respectively], as was previous smoking for men (OR 2.3, 95% CI 1.2-4.4). There
      were also indications of relationships between previous use of a private well and
      RA in both men and women. CONCLUSION: Several previously published associations
      have been reproduced in the present study, which also generates some new
      hypotheses that suggest further research.

PMID- 15513678
TI  - Quantitative assessment of periarticular osteopenia in patients with early
      rheumatoid arthritis: a preliminary report.
AB  - BACKGROUND: Involvement of the metacarpophalangeal (MP) joints is one of the
      major problems in patients with rheumatoid arthritis (RA). Although several data
      about the cumulative influence of steroid intake on bone are available, the
      course of demineralisation in RA has not been described by quantitative methods
      until now. PATIENTS AND METHODS: Computed tomography (CT) sections of 96 MP
      joints in 12 RA patients and of 32 MP joints in four age-matched healthy controls
      were investigated. Patients were classified according to Steinbrocker.
      Densitometric evaluation of subchondral bone density was performed by CT
      osteoabsorptiometry (CT-OAM). Quantitative CT-OAM was used to evaluate
      mineralisation of the articular surfaces in MP joints. RESULTS: In the distal
      articular surface of MP joints, the number of density maxima was reduced from 3
      to 2.1+/-0.3, 1.9+/-0.5 and 1.3+/-0.3 in RA patients with early, mild to
      moderate, and severe disease, respectively. Means of calcium concentrations were
      633.4+/-35. 3 mg Ca2+/mL, 518.9+/-56.2 mg Ca2+/mL, 497.7+/-23.8 mg Ca2+/mL and
      455.1+/-28.6 mg Ca2+/mL for controls and RA patients with early, mild to
      moderate, and severe RA, respectively. Mineralisation of the distal articular
      surface was significantly reduced in all groups of RA patients [probability (p) =
      0.005]. Regarding the number of density maxima, no differences were detected in
      the proximal articular surface of normal and RA fingers. However, mineralisation
      of the proximal articular surface was significantly reduced in all groups of RA
      patients (p = 0.004). Means of calcium concentrations of the proximal articular
      surface were 494.1+/-48.5 mg Ca2+/mL, 413.0+/-16.2 mg Ca2+/mL, 406.0+/-51.4 mg
      Ca2+/mL, 390,4+/-41.1 mg Ca2+/mL for controls and RA patients with early, mild to
      moderate, and severe RA, respectively. CONCLUSION: Patients with early and
      untreated RA show loss of mineralisation and altered morphology of the MP joints
      of the hand, even before corticosteroid therapy. CT-OAM provides evidence for an
      early alteration of functional anatomy in MP joints.

PMID- 15513679
TI  - Factors affecting clinical and therapeutic outcomes of patients with juvenile
      rheumatoid arthritis.
AB  - OBJECTIVE: To investigate clinical features, medications, and therapeutic
      responses of juvenile rheumatoid arthritis (JRA) among Taiwanese children.
      METHODS: A retrospective chart review was conducted among all children newly
      diagnosed with JRA at the National Taiwan University Hospital between 1996 and
      2001. RESULTS: Forty boys and 30 girls were enrolled in the study. The mean
      follow-up was 45 months. Oligoarticular onset was the most common type. A bimodal
      distribution of age at onset was observed, with peaks at 4 and 10 years. All
      patients received non-steroidal anti-inflammatory drugs (NSAIDs); 27 (39%)
      received corticosteroids, and 44 (63%) had second-line drugs during the first
      course of treatment. Forty-three patients (69%) achieved clinical remission after
      a mean of 14.8 months of medication, and 19 (31%) were drug-dependent. The major
      factors related to the failure of first remission were human leukocyte antigen
      B27 (HLA-B27), high C-reactive protein (CRP) level, and thrombocytosis at
      diagnosis. CONCLUSION: There are different phenotypic features among Taiwanese
      children with JRA. Factors related to the failure of first remission were HLA
      B27, high CRP level, and thrombocytosis at diagnosis.

PMID- 15513680
TI  - The effect of HLA-DR antigens on the susceptibility to, and clinical expression
      of psoriatic arthritis.
AB  - OBJECTIVE: To analyse the relative role of HLA-DR antigens in the susceptibility
      to, and clinical expression of psoriatic arthritis (PsA). PATIENTS AND METHODS: A
      retrospective cohort study of 120 patients with PsA who were assessed according
      to a standard protocol. Patients were classified in accordance with the
      predominant pattern observed in the last 5 years of disease evolution:
      polyarthritis (n = 33), oligoarthritis (n = 45), and spondylitis (n = 42). HLA-Cw
      gene typing was done by the polymerase chain reaction (PCR) sequence-specific
      oligonucleotide probes (PCR-SSOP) method, while HLA-DR and B27 typing were
      performed by serological methods. The distribution of HLA-DR and Cw antigens was
      also analysed in 50 patients with psoriasis alone. One hundred and seventy
      subjects from our general population served as controls. RESULTS: No definite
      association was found between HLA-DR alleles and the risk of psoriasis or PsA.
      HLA-DR4 was found to be under-represented in arthritic patients [probability (p)
      = 0.03]. HLA-DR7 showed association with oligoarthritis [odds ratio (OR) 6, 95%
      confidence interval (CI): 2-16, corrected probability (Pc) = 0.01], whereas HLA
      DR8 appeared to be related to the risk of polyarthritis (OR 9.5, 95% CI: 2-42, Pc
      = 0.02). HLA-Cw*0602 conferred risk for psoriasis (Pc < 0.00001), but not for
      PsA. As expected, HLA-B27 appeared to be over-represented in patients with
      spondylitis (p = 0.03). CONCLUSIONS: This is the first report that associates HLA
      DR8 with psoriatic polyarthritis. Although HLA-DR antigens have a marginal role
      in PsA or psoriasis susceptibility, they may be relevant to the modulation of the
      clinical expression of PsA. These HLA data add support to the classification of
      PsA into three disease subsets.

PMID- 15513681
TI  - Therapeutic efficacy and safety of multiple intravenous infusions of infliximab
      in refractory ankylosing spondylitis patients with axial involvement.
AB  - OBJECTIVE: To evaluate the clinical response and safety profile of infliximab in
      refractory ankylosing spondylitis patients. METHODS: Patients with active
      ankylosing spondylitis, despite methotrexate therapy, were included in an open
      label, single-centre study. Patients were given 3-5 mg/kg infliximab infusions at
      Weeks 0, 2, 6, and q8 etc up to Week 30, together with methotrexate at the dosage
      taken prior to study inclusion, and were followed-up for a 34-week period.
      RESULTS: Nine patients with mean age 43 years and mean disease duration 7 years,
      diagnosed with pure axial ankylosing spondylitis were included. Erythrocyte
      sedimentation rate (ESR), C-reactive protein (CRP), duration of morning
      stiffness, physician's global assessment of disease activity (PhGADA), visual
      analogue scale (VAS) pain, enthesis index, occiput-to-wall test, Bath Ankylosing
      Spondylitis Disease Activity Index (BASDAI), and Bath Ankylosing Spondylitis
      Functional Index (BASFI) significantly improved by Week 6. No adverse events
      related with the drug were recorded during the 34-week follow-up period.
      CONCLUSION: Efficacy results are similar to those previously published. No
      adverse events were seen during therapy, and antinuclear antibody profiles were
      negative. The association of methotrexate with infliximab can improve the safety
      profile.

PMID- 15513682
TI  - Heel fat pad involvement in rheumatoid arthritis and in spondyloarthropathies: an
      ultrasonographic study.
AB  - BACKGROUND: Heel fat pad inflammation and degeneration have been frequently
      proved to cause talalgia. Painful heel fat pad is often confused with plantar
      fasciitis, and only magnetic resonance imaging (MRI) or ultrasonography (US) can
      differentiate these conditions. Scanty data are available about heel fat pad
      involvement in the course of chronic polyarthritis. OBJECTIVE: To investigate
      with US the heel fat pad involvement in patients with rheumatoid arthritis (RA)
      and spondyloarthropathies (SpA); to describe and compare the clinical and
      sonographic features of this lesion in the two groups. METHODS: The heels of 181
      consecutive outpatients with RA and 160 with SpA were studied by US and
      radiography. A control group of 60 healthy subjects was examined by US. RESULTS:
      Two different patterns of involvement of the heel fat pad were observed. The
      inflammatory-oedematous pattern was more frequent in patients with RA (6.6%) than
      in those with SpA (1.8%), and was associated with talalgia--even if it was not
      associated with plantar fasciitis or enthesophyte (bony spur). The degenerative
      atrophic pattern was less frequent (1.1% in RA, 1.9% in SpA), and was associated
      with plantar fasciitis and subcalcaneal enthesophyte. CONCLUSIONS: The
      inflammatory-oedematous lesion of the heel fat-pad is relatively frequent in RA
      and causes subcalcaneal pain. Degenerative-atrophic changes of the heel fat pad
      can be observed in RA and SpA, and seem to be associated with chronic
      abnormalities of the plantar fascia and of its enthesis.

PMID- 15513683
TI  - MRI abnormalities of sacroiliac joints in early spondylarthropathy: a 1-year
      follow-up study.
AB  - OBJECTIVE: To describe changes in chronic and acute magnetic resonance imaging
      (MRI) abnormalities of the sacroiliac joints (SIJs) in early spondylarthropathy
      (SpA), and to associate these findings with computed tomography (CT), X-ray, and
      clinical findings during a 1-year follow-up. METHODS: Thirty-four patients, 20
      males and 14 females, median age 27 years, with inflammatory low back pain
      (median 23 months) were included. MRI, CT, and X-ray, as well as clinical and
      laboratory tests were performed. After a follow-up period of 1 year (median 377
      days) the examinations were repeated, and the findings were correlated. RESULTS:
      MRI and CT changes resulting from SIJ destruction increased significantly during
      follow-up, and the two modalities were significantly correlated. For the MRI
      findings of inflammatory activity, only bone marrow oedema decreased
      significantly. An increase in the Schober test was the only clinical examination
      that changed significantly. CONCLUSION: In early SpA, MRI can detect significant
      inflammatory and destructive changes of the SIJs over a 1-year follow-up period,
      in spite of minimal changes in the clinical parameters. The MRI changes in
      inflammatory activity are not detectable by CT and X-ray examinations. Thus, MRI
      may be a sensitive method, without known risks, for early diagnosis and for
      following disease progression in SpA.

PMID- 15513684
TI  - Intravenous cyclophosphamide for lupus nephritis in Thai children.
AB  - OBJECTIVE: To evaluate the efficacy of a 36-month course of intravenous
      cyclophosphamide therapy for severe lupus nephritis in Thai children between
      October 1993 and December 2000. METHODS: Intravenous cyclophosphamide combined
      with oral prednisolone was given for 36 months to patients with systemic lupus
      erythematosus (SLE) who had severe renal involvement. Serum creatinine (Cr),
      creatinine clearance (CCr), urinary protein, C3, and complete blood count (CBC)
      were measured each visit for intravenous cyclophosphamide. Repeated measures
      ANOVA and Kaplan-Meier survival analysis were used. RESULTS: Of 21 patients
      enrolled in the study, three died and two were lost to follow-up, leaving 16
      patients who completed therapy (13 females and three males) with age at diagnosis
      12.1+/-2.3 years (range 7.2-20.6 years). The follow-up period was 6.3+/-2.3 years
      (range 3.3-13.8 years). Fourteen patients had lupus nephritis WHO classification
      class IV and two had lupus nephritis WHO classification class II. Hypertension
      was detected in ten patients. Lowess smoothing curves and repeated measures ANOVA
      indicated no significant change in Cr and CCr [probability (p) > 0.05)], but
      significantly increased C3 and haemoglobin and significantly decreased urinary
      protein and white blood cell count (p < 0.001). Five patients had six episodes of
      acute renal failure; one died, renal function returned to normal in two patients,
      two continued to chronic renal failure, and one died of chronic renal failure.
      The 5-year survival and renal survival were 86.5% and 87.5% (95% CI 55.8-96.5%
      and 58.6-96.7%), respectively. CONCLUSION: Intravenous cyclophosphamide in severe
      lupus nephritis in Thai children showed a satisfactory outcome with minimal
      complications. Further follow-up is needed.

PMID- 15513685
TI  - Long-term follow-up study of pulmonary findings in patients with primary
      Sjogren's syndrome.
AB  - BACKGROUND: In a previous study pulmonary hyperinflation was observed frequently
      in patients with primary Sjogren's syndrome (pSS) and elevated serum beta-2
      microglobulin (beta2m) concentrations were associated with hyperinflation.
      OBJECTIVE: To evaluate the significance of baseline serum beta2m concentration
      and to identify other possible risk factors for pulmonary involvement in long
      term follow-up of patients with pSS. METHODS: Nineteen pSS patients whose
      pulmonary function tests (PFTs) had been previously studied were reexamined after
      a median follow-up of 10 years. Pulmonary symptoms were recorded, chest
      radiograph, and high-resolution computed tomography (HRCT) were evaluated and
      methacholine provocation and PFTs including flow-volume spirometry, body
      plethysmography, and diffusing capacity performed. RESULTS: Baseline serum beta2m
      concentrations correlated inversely with follow-up total lung capacity (TLC),
      vital capacity (VC), and diffusing capacity (DL), and positively with residual
      volume (RV), all expressed as percentage of predicted values. Diminished airways
      resistance (Raw) and, correspondingly, elevated specific conductance (SGaw) were
      frequent findings in pSS patients at follow-up, indirectly implying stiffness of
      the lungs and a restrictive decrease in lung volumes. Baseline serum protein
      concentration was higher and IgG concentration tended to be higher in pSS
      patients who at follow-up had elevated SGaw compared with others. Interstitial
      changes in HRCT were found more frequently in patients with elevated SGaw than in
      those without. CONCLUSION: Our results suggest that subtle restrictive changes in
      pulmonary function are more prone to develop in the long term in pSS patients
      with elevated serum beta2m concentration and other signs of immunological
      activity at baseline.

PMID- 15513686
TI  - A novel murine model of orthopaedic wear-debris associated osteolysis.
AB  - OBJECTIVE: To develop a mouse model of bone resorption to quantitatively evaluate
      wear-debris induced osteolysis. METHODS: Air pouches were established on the back
      of BALB/c mice, followed by the surgical introduction of a section of femur or
      calvaria from a syngeneic mouse donor. One group of bone-implanted pouches was
      stimulated with ultra-high molecular weight polyethylene (UHMWPE) debris, and the
      remaining bone-implanted pouches received saline alone as controls. The tissues
      were harvested at 2, 7, and 14 days after bone implantation for molecular and
      histological analyses. RESULTS: Marked inflammatory responses (thicker membrane
      and increased cellular infiltration) were observed in UHMWPE-stimulated pouches,
      compared with the saline control. Intensive tartrate-resistant acid phosphatase
      (TRAP) staining was identified in the UHMWPE-stimulated pouches, especially at
      the attachment site of inflammatory tissue with implanted bone, where active
      osteolysis occurred. Image analysis showed that the bone collagen loss was
      closely related to the amount of UHMWPE within the tissue, and was most prevalent
      at the contact site of bone with inflammatory tissue. UHMWPE stimulation also
      significantly increased the release of free calcium into the pouch fluids.
      CONCLUSION: This model demonstrates a sensitive, rapid, and reproducible method
      for studying wear-debris induced osteolysis seen in patients with aseptic
      loosening.

PMID- 15513687
TI  - Neuro-Behcet's disease--rapidly reversible with early diagnosis and treatment.
AB  - Behcet's disease is an idiopathic multi-systemic, inflammatory disorder that may
      affect major organs, including the central nervous system. It is a clinical
      diagnosis, and a history of recurrent oral and genital ulcers should be elicited,
      especially in cases of unexplained uveitis with atypical neurological symptoms.
      We describe the rapid neurological recovery and neuroimaging changes following
      high-dose systemic corticosteroids in a 44-year-old man with recurrent oral
      ulcers, panuveitis, and acute neuro-Behcet's, presenting with
      meningoencephalitis. Early diagnosis with the aid of appropriate neuroimaging and
      immunosuppressive therapy prevented long-term neurological complications.
      Appropriate neuroimaging can facilitate early diagnosis and treatment, and
      provide prognostic information on neuro-Behcet's.

PMID- 15513688
TI  - Behcet's disease in Moroccan children: a report of 12 cases.
AB  - We report 12 cases of Behcet's disease (BD) in children. The mean age of symptom
      onset was 12.4 years. Four patients (33.3%) had a past familial history of BD.
      Clinical manifestations were: oral aphtosis (n = 12), genital aphtosis (n = 9),
      ocular involvement (n = 9), neuro-Behcet (n = 6), venous thrombosis (n = 4),
      articular involvement (n = 3), and entero-Behcet (n = 1). All patients but one
      were initially treated with steroids; three cases with ocular involvement were
      treated with chlorambucil; and three other cases of neuro-Behcet were treated
      with cyclophosphamide. After a mean follow-up of 4 years, four patients with
      neurological involvement developed steroid-dependence with recurrence of
      symptoms. Four patients had optic atrophy with blindness.

PMID- 15513689
TI  - Assessment of total body potassium in healthy Italian men.
AB  - BACKGROUND: Whole-body (40)K counting is a valuable tool for assessing cellular
      changes in body composition with ageing. AIM: The objectives of this study were
      to assess total body potassium (TBK) and body cell mass (BCM) differences with
      age, and to compare TBK and BCM between individuals with a body mass index (BMI)
      < 25 kg m(-2) versus > 25 kg m(-2). SUBJECTS AND METHODS: Body composition of 840
      healthy Italian men, 18-70 years of age, was measured by whole-body counting of
      (40)K. BCM (kg) was calculated as 0.00833 x TBK (mmol). RESULTS: Body weight did
      not differ among groups. TBK, TBK/height, TBK/body weight, and BCM were
      significantly lower for the 51-70-year-old group compared with all other groups.
      The 51-70-year-old group with a BMI < 25 kg m(-2) had significantly lower TBK,
      TBK/height, and BCM than all other decades with a BMI < 25 kg m(-2); whereas
      TBK/body weight was significantly lower than the 18-30 and 31-40-year-old groups.
      The 51-70-year-old group with a BMI > 25 kg m(-2) had significantly lower TBK,
      TBK/height, TBK/body weight, and BCM than all other decades with a BMI > 25 kg m(
      2). CONCLUSION: TBK and BCM decrease significantly with ageing, which could
      result in decreased functional capacity in older adults.

PMID- 15513690
TI  - Short-term growth of premature infants treated with dexamethasone assessed by
      mini-knemometry.
AB  - AIM: The study aimed to measure the direct effect of dexamethasone (DEXA) on
      daily lower leg length per mini-knemometry of premature infants and to examine
      whether the administration of different doses is associated with alternations in
      growth. PATIENTS AND METHODS: We observed 20 premature children and had 276
      complete mini-knemometrical and weight measurements (13.8 measurements per single
      child) for analysis. The gestational age of the infants was 26.8 +/- 1.9 weeks;
      the mean birth weight was 973 +/- 336 g. All infants underwent daily measurements
      of lower leg length performed by mini-knemometry. We divided the 41 DEXA
      administrations into three subgroups. Group I included a cumulative dose of 0.75
      mg DEXA per kg bodyweight (BW), group II doses between 0.75 and 1.0 mg per kg BW
      and group III dosages above 1.0 mg per kg BW. RESULTS: We observed catch-up
      growth in group I within 24 h after stopping therapy. Groups II and III needed 48
      72 h to achieve a normal level in short-term growth. CONCLUSION: Lower doses
      seemed to have an equivalent effect without long-term effect on lower leg length.
      In higher doses (groups II and III) the growth was suppressed for more than 24 h.

PMID- 15513691
TI  - Risk factors for breast cancer in Pakistani women aged less than 45 years.
AB  - BACKGROUND: There has been an increase in the incidence of breast cancer in
      previously low-risk Asian countries. It is important to identify the risk factors
      for Asian women, as little information currently exists for this population. AIM:
      The objective of the study was to determine risk factors for breast cancer among
      Pakistani women. SUBJECTS AND METHODS: 498 cases younger than 45 years were
      interviewed from 1 July 1997 to 31 December 1998 at two major cancer hospitals.
      Age-matched population-based controls were selected from two cities and two
      villages to represent urban and rural areas. For the variables under study, cases
      and controls were compared by t-test. Conditional multiple logistic regression
      models were applied to the data set. RESULTS: Women with BMI >or= 30, with a
      family history of breast cancer and who were parous were at increased risk. Among
      parous women risk factors included BMI >or= 30, being in a consanguineous
      marriage, later age at menarche, later age at first full-term pregnancy, high
      parity and a history of abortion. CONCLUSION: The risk factors identified for
      Pakistani women below 45 years were similar to those observed in other studies.
      However, obesity in pre-menopausal women and late menarche were not protective
      and consanguinity was identified as a risk.

PMID- 15513692
TI  - Skeletal maturity and socio-economic status in Portuguese children and youths:
      the Madeira growth study.
AB  - BACKGROUND: Skeletal maturity is used to evaluate biological maturity status.
      Information about the association between socio-economic status (SES) and
      skeletal maturity is limited in Portugal. AIMS: The aim of this study is to
      document the skeletal maturity of youths in Madeira and to evaluate variation in
      maturity associated with SES. SUBJECTS AND METHODS: The study involved 507
      subjects (256 boys and 251 girls) from the Madeira Growth Study, a mixed
      longitudinal study of five cohorts (8, 10, 12, 14 and 16 years of age) followed
      at yearly intervals over 3 years (1996-1998). A total of 1493 observations were
      made. Skeletal age was estimated from radiographs of the hand and wrist using the
      Tanner-Whitehouse 2 method (TW2). Social class rankings were based on method.
      Five social rankings were subsequently grouped into three SES categories: high,
      average and low. RESULTS: Median for the radius, ulna and short finger bones (RUS
      scores) in the total sample of boys and girls increased curvilinearly across age
      whereas median for the 7 (without pisiform) carpal bones (Carpal scores)
      increased almost linearly. The 20-bone maturity scores demonstrated distinctive
      trends by gender: the medians for boys increased almost linearly while the
      medians for girls increased curvilinearly. SES differences were minimal. Only
      among children aged 10-11 years were high SES boys and girls advanced in skeletal
      maturity. Madeira adolescents were advanced in skeletal maturity compared with
      Belgian reference values. CONCLUSION: The data suggests population variation in
      TW2 estimates of skeletal maturation. Skeletal maturity was not related to SES in
      youths from Madeira.

PMID- 15513693
TI  - TW3 bone age: RUS/CB and gender differences of percentiles for score and score
      increments.
AB  - BACKGROUND: Longitudinal data on bone age progression is scarce. AIM: The study
      aimed to present reference values for Tanner-Whitehouse 3 (TW3) bone age score
      and score increments, and to provide means and standard deviations of appearance
      time for all TW3 stages. Gender differences and differences between radio ulna
      and short bones (RUS) and carpal bone (CB) scores were studied. SUBJECTS AND
      METHODS: Bone age data collected for ages 3 months to 20 years in 232 subjects
      during the First Zurich Longitudinal Study (1954-1976) were used. Smoothed
      empirical percentiles of TW3 RUS and CB scores for age, of score increments for
      age and of score increments for attained score are presented. Means and standard
      deviations of the appearance times are calculated by parametric censored
      regression. RESULTS: There are clear differences between the RUS and CB scores
      and between the genders. Boys are delayed with respect to girls, with different
      delays for RUS and CB. For RUS, differences in maturation reflect the known
      differences of physical growth, with a later and more intense peak in boys. For
      CB, there is little difference in timing and intensity. However, girls reach the
      final score about 2 years earlier than boys. The consistently earlier mean
      appearance times in girls indicate that skeletal maturation is, already in
      childhood, more rapid in girls than in boys. There are significant gender
      differences in the sequence of appearance. CONCLUSION: Reference values for TW3
      score and score increments and mean appearance times for stages add to existing
      knowledge and indicate important RUS/CB and gender differences, whose sources are
      largely unknown.

PMID- 15513695
TI  - Pubertal timing and educational careers: a longitudinal study.
AB  - BACKGROUND: Pubertal timing is related to several dimensions of adolescent
      development. No studies concern its associations with educational careers. AIM:
      To investigate whether pubertal timing predicts attained educational level and
      how school achievement, educational track and sociodemographic background in
      adolescence mediate this relationship. SUBJECTS AND METHODS: Survey data (1981,
      1983, 1985) from samples of 12-16-year-old Finns (n = 7674) were linked with the
      respondents' attained education in 1998 (ages 27-33). Ages of menarche and of
      first ejaculation were indicators of pubertal timing. RESULTS: Among boys who by
      age 16 had experienced early, average or late pubertal timing, 13%, 12%, and 6%
      reached upper tertiary educational level, respectively. Boys with early or
      average puberty often came from high social strata and selected educational
      tracks with good prospects. In girls, sociodemographic factors rather than
      pubertal timing predicted attained educational level. CONCLUSIONS: Early or
      average onset of puberty plays a role in dividing boys into educational tracks
      after compulsory schooling. Support should be given to boys, whose delayed
      pubertal development makes them immature to making appropriate educational
      decisions and to boys who may have experienced early puberty but fail to exploit
      educational opportunities available for them.

PMID- 15513694
TI  - Can greater muscularity in larger individuals resolve the 3/4 power-law
      controversy when modelling maximum oxygen uptake?
AB  - BACKGROUND: The power function relationship, MR = a.m(b), between metabolic rate
      (MR) and body mass m has been the source of much controversy amongst biologists
      for many years. Various studies have reported mass exponents (b) greater than the
      anticipated 'surface-area' exponent 0.67, often closer to 0.75 originally
      identified by Kleiber. AIM: The study aimed to provide a biological explanation
      for these 'inflated' exponents when modelling maximum oxygen uptake (max), based
      on the observations from this and previous studies that larger individuals
      develop disproportionately more muscle mass in the arms and legs. RESEARCH DESIGN
      AND SUBJECTS: A cross-sectional study of 119 professional soccer players from
      Croatia aged 18-34 was carried out. RESULTS: Here we confirm that the power
      function relationship between max and body mass of the professional soccer
      players results in an 'inflated' mass exponent of 0.75 (95% confidence interval
      from 0.56 to 0.93), but also the larger soccer players have disproportionately
      greater leg muscle girths. When the analysis was repeated incorporating the calf
      and thigh muscle girths rather than body mass as predictor variables, the
      analysis not only explained significantly more of the variance in max, but the
      sum of the exponents confirmed a surface-area law. CONCLUSIONS: These findings
      confirm the pitfalls of fitting body-mass power laws and suggest using muscle
      girth methodology as a more appropriate way to scale or normalize metabolic
      variables such as max for individuals of different body sizes.

PMID- 15513696
TI  - Association between somatotypes and blood pressure in an adult Chuvasha
      population.
AB  - BACKGROUND: The relationship between blood pressure (BP) and anthropometrical
      characteristics has been indeed examined extensively, but only a few studies have
      investigated any connection of somatotypes to BP. AIMS: to evaluate the
      association between BP and various anthropometrical characteristics, including
      components of somatotypes (using the methods of Heath and Carter and of
      Deriabin). SUBJECTS AND METHODS: The study sample comprised 783 males aged 18-89
      years and 720 females aged 18-90 years, all residents of the Chuvasha, Russian
      Federation. We used multiple regression, Pearson's and canonical correlation
      analyses. RESULTS: Significant correlations (r = 0.19-0.28, p < 0.05) were
      obtained between BP and anthropometric characteristics associated with body
      compositions and somatotypes. The most impressive were the canonical correlations
      between BP and somatotype components derived according to Heath and Carter
      (0.275), and according to Deriabin's (0.333) method. Different body types were
      highly significantly (P < 0.001) associated with systolic and diastolic BP.
      CONCLUSION: Individuals of robust physique (with high endomorphy and mesomorphy)
      showed high mean values of systolic and diastolic BP, whereas the smallest
      persons had the lowest BP values. These findings suggest the existence of common
      physiological paths in the development of body physique and blood pressure
      regulation and may possibly be indicative of the involvement of pleiotropic
      genetic and/or epigenetic mechanisms in this regulation.

PMID- 15513698
TI  - Age of onset of pubertal characteristics in boys aged 6-14 years of the Province
      of L'Aquila (Abruzzo, Italy).
AB  - BACKGROUND: Previous results on growth patterns of children from central-southern
      Italy (Abruzzo region) showed an increasing tendency to obesity and suggested
      that the secular trend was still in progress in this region. However, data on
      pubertal development was lacking. OBJECTIVE: The objective of the study was to
      provide population data on pubertal development in a sample of 535 boys aged 6-14
      years as a contribution to the ongoing debate on earlier onset of pubertal traits
      and on the slowing down of the secular trend. METHODS: A cross-sectional survey
      was used. Data for genital and pubic hair development (GD and PHD) were analysed
      by probit analysis. RESULTS: The boys start developing sexual characteristics at
      age 9: 13.3% had entered stage 2 of GD and 8.9% showed PHD. At 13 years of age,
      5% and 7.4% were still in stage 1 of GD and PHD, respectively, whereas almost one
      third had attained stage 5 for both sexual characteristics. The median age for
      attainment of stage 2 was 11.2 years for GD, 11.5 years for PHD and 11 years for
      one or both of them. CONCLUSIONS: These results are in line with those for
      several European and industrialized countries and do not show a significantly
      earlier onset of sexual maturation.

PMID- 15513697
TI  - Serum electrolyte, serum protein, serum fat and renal responses to a dietary
      sodium challenge: allostasis and allostatic load.
AB  - OBJECTIVE: The purpose of this study was to assess, in borderline hypertensive
      subjects, the homeostatic and allostatic responses of serum electrolytes,
      proteins, lipids, hematocrit and renal function to an extreme dietary sodium
      challenge, and to evaluate whether the responses in these clinical parameters
      were associated with a concomitant response in blood pressure. SUBJECTS AND
      METHODS: Data from middle-aged adults with a diagnosis of mild, uncomplicated
      borderline hypertension were collected at the end of 1-month randomized trials of
      low (24 +/- 13 mmol/day) and high (309 +/- 88 mmol/day) dietary sodium intake. A
      total of 48 subjects (38 men and 10 women) were examined. RESULTS: Serum sodium
      increased (p < 0.001), while all other serum electrolytes, except chloride,
      decreased (p < 0.01) from the low to high sodium diets. Serum proteins (p < 0.05)
      and hematocit (p < 0.001) also declined among subjects on a high sodium diet.
      However, creatinine clearance (an indicator of glomerular filtration) increased
      with sodium intake (p = 0.004). None of these biochemical or renal functional
      responses was associated with a change in blood pressure. CONCLUSION: There are
      modest yet significant changes in serum electrolytes associated with changes in
      dietary sodium intake, suggesting that these ions are under an allostatic control
      mechanism. Serum proteins also appear to function as allostatic compensatory
      mechanisms, offsetting the net effect of increased serum salinity. It is
      speculated that the adaptive allostatic renal response to a high sodium diet (an
      increase in GFR) may result in loss of the ability to appropriately vary renal
      filtration if that diet is chronically maintained.

PMID- 15513707
TI  - Collagenase predigestion on paraffin sections enhances collagen
      immunohistochemical detection without distorting tissue morphology.
AB  - Reliable immunohistochemical detection of collagen in formalin fixed, paraffin
      embedded tissues requires protease digestion. While these pan-proteases (pepsin,
      trypsin, protease K, etc.) enhance collagen detection, they also digest many
      other tissue proteins and produce poor cellular morphology and unrecognizable
      cellular structures. Balancing the conditions (protease type, concentration,
      incubation time and temperature) to digest some, but not all, proteins in a
      tissue section while optimizing collagen detection requires one to compromise
      improved collagen immunolabeling with adequate cellular morphology. Furthermore,
      optimal conditions for digesting tissue proteins to enhance collagen detection
      vary among tissue types and their fixation. Although brain is not typically
      subject to these deleterious consequences, structures such as epithelium,
      spermatids, stroma etc. and other tissues with complicated histology are
      profoundly affected. To resolve this technical dilemma, we discovered a novel use
      for collagenase to enhance collagen immunodetection without affecting the
      noncollagen proteins, thereby preserving tissue morphology. Collagenase, which is
      typically used in vitro for disassociation of cells, has never been used reliably
      on formalin fixed, paraffin embedded tissue sections. This new use of collagenase
      for immunohistochemistry promotes increased collagen immunolabeling, is easy to
      use, is versatile, and allows preservation of tissue structure that provides
      maximal and accurate histological information.

PMID- 15513708
TI  - Effects of dimethylsulfoxide on the ultrastructure of fixed cells.
AB  - It has been reported that the use of dimethylsulfoxide (DMSO) as a solvent for
      fixatives enhances preservation of cellular ultrastructure. By contrast, we have
      shown that DMSO alters the ultrastructural integrity of glutaraldehyde fixed
      cells. The cell membrane, nuclear envelope, endoplasmic reticulum, ribosomes,
      microtubules and intracytoplasmic organelles are most susceptible to the action
      of DMSO. We hypothesize that DMSO exerts intracellular alterations via its
      interaction with remnant interfacial water in fixed cells. DMSO-induced
      alterations of these and related cellular components may result in the formation
      of artefactual structures and networks. Thus, it appears that DMSO containing
      glutaraldehyde neither accelerates fixation nor enhances stabilization of
      cellular ultrastructure. For these reasons, addition of DMSO to fixatives is not
      recommended.

PMID- 15513709
TI  - Photochemistry of dyes and fluorochromes used in biology and medicine: some
      physicochemical background and current applications.
AB  - An overview of the basic principles of photochemistry is presented to facilitate
      discussion of fluorescence, quenching and quantum yields. These topics in turn
      provide the foundation for an account of fluorescence spectroscopy and its
      application to microscopy. A brief overview of light microscopy and the
      application of fluorescence microscopy is given. The influences of molecular
      features, such as aromatic character and substitution patterns, on color and
      fluorescence are described. The concept of color fading is considered with
      particular reference to its effect on microscopic preparations. A survey of
      representative fluorescent probes is provided, and their sensitivity,
      application, and limitations are described. The phototoxicity of fluorescent
      molecules is discussed using biomembranes and DNA as examples of targets of
      toxicity. Photodynamic therapy, a relatively new clinical application of
      phototoxicity, is described. Both anticancer and antimicrobial applications are
      noted, and an assessment is given of the current ideas on the ideal
      physicochemical properties of the sensitizing agents for such applications.

PMID- 15513710
TI  - Histochemical assay to detect class III ADH activity in situ in Arabidopsis
      seedlings.
AB  - Whole-mount detection methods are quick, inexpensive and offer the possibility of
      studying the temporal and spatial patterns of gene expression in a morphological
      context. These methods have been used widely to detect messenger RNAs and to
      measure enzymatic activity of reporter genes, such as beta-galactosidase or beta
      glucuronidase. Taking advantage of the fact that NADH generated during the
      oxidation of formaldehyde by class III alcohol dehydrogenase can reduce the
      compound nitroblue tetrazolium to form a blue precipitate, we have developed a
      new method to detect class III alcohol dehydrogenase activity in situ in whole
      Arabidopsis plants. This reaction has been used earlier for in situ
      electrophoresis detection and for histochemical analysis in animal tissue
      sections. With a few modifications, it can be used in whole Arabidopsis plants or
      excised plant tissues to allow a rapid analysis of class III ADH activity during
      development or in response to elicitors. The method might be extended to other
      dehydrogenases by using specific substrates.

PMID- 15513711
TI  - Observations of aspergillosis in the brains of turkey poults using different
      histopathological staining techniques.
AB  - Different staining methods were evaluated for studying aspergillosis of the
      central nervous system (CNS). The pathological changes and fungal elements in
      cerebrum and cerebellum of 17 turkey poults with aspergillosis were examined and
      described. Tissue sections were stained with hematoxylin-eosin (HE), Kluver
      Barrera's and Grocott's methods, and periodic acid-Schiff (PAS). Focal
      granulomatous reactions with central necrosis were observed in the HE stained
      slides. Fungal hyphae were easily demonstrated using Grocott's method and PAS.
      These two methods, however, were not suitable for describing detailed
      histopathological changes. The Kluver-Barrera method was used to demonstrate the
      neural tissue reaction. Neurons were found to be sensitive to aspergillosis, in
      contrast to glial cells that showed fewer pathological changes. The fungal
      elements were clearly visible with the Kluver-Barrera method, resulting in better
      information about the interactions of neural tissue, the inflammatory response,
      and the fungus. The use of the Kluver-Barrera method for this purpose has not
      been documented previously.

PMID- 15513713
TI  - The M'Fadyean reaction: a stain for anthrax bacilli.

PMID- 15513712
TI  - Detection of the protozoan Neospora caninum using in situ polymerase chain
      reaction.
AB  - A new method to detect the protozoan Neospora caninum using indirect in situ
      polymerase chain reaction (PCR) is described. In situ PCR combines the advantages
      of the extraordinarily high sensitivity and specificity of PCR and the in situ
      representation of immunohistochemical methods. We describe an indirect in situ
      PCR, whereby the amplified products were detected using a primed in situ (PRINS)
      reaction with hapten-labeled nucleotides and visualized using fluorochrome
      labeled antibodies. This technique was carried out in both infected cell cultures
      and formalin fixed, paraffin embedded tissues. Clear signals were obtained in the
      N. caninum positive samples using in situ PCR, whereas control slides with
      Toxoplasma gondii infected tissues always yielded negative results.

PMID- 15513714
TI  - Foot positioning instruction, initial vertical load position and lifting
      technique: effects on low back loading.
AB  - This study investigated the effects of initial load height and foot placement
      instruction in four lifting techniques: free, stoop (bending the back), squat
      (bending the knees) and a modified squat technique (bending the knees and
      rotating them outward). A 2D dynamic linked segment model was combined with an
      EMG assisted trunk muscle model to quantify kinematics and low back loading in 10
      subjects performing 19 different lifting movements, using 10.5 kg boxes without
      handles. When lifting from a 0.05 m height with the feet behind the box, squat
      lifting resulted in 19.9% (SD 8.7%) higher net moments (p < 0.001) and 17.0% (SD
      13.2%) higher compression forces (p < 0.01) than stoop lifting. This effect was
      reduced to 12.8% (SD 10.7%) for moments and a non-significant 7.4% (SD 16.0%) for
      compression forces when lifting with the feet beside the box and it disappeared
      when lifting from 0.5 m height. Differences between squat and stoop lifts, as
      well as the interaction with lifting height, could to a large extent be explained
      by changes in the horizontal L5/S1 intervertebral joint position relative to the
      load, the upper body acceleration, and lumbar flexion. Rotating the knees outward
      during squat lifts resulted in moments and compression forces that were smaller
      than in squat lifting but larger than in stoop lifting. Shear forces were small (
      < 300 N) at the L4/L5 joint and substantial (1100 - 1400 N) but unaffected by
      lifting technique at the L5/S1 joint. The present results show that the effects
      of lifting technique on low back loading depend on the task context.

PMID- 15513715
TI  - Towards understanding the workspace of human limbs.
AB  - Significant attention in recent years has been given towards obtaining a better
      understanding of human joint ranges, measurement, and functionality, especially
      in conjunction with commands issued by the central nervous system. Studies of
      those commands often include computer algorithms to describe path trajectories.
      These are typically in "open-form" with specific descriptions of motions, but not
      "closed form" mathematical solutions of the full range of possibilities. This
      paper proposes a rigorous "closed form" kinematic formulation to model human
      limbs, understand their workspace (also called the reach envelope), and delineate
      barriers therein where a path becomes difficult or impossible owing to physical
      constraints. The novel ability to visualize barriers in the workspace emphasizes
      the power of these closed form equations. Moreover, this formulation takes into
      account joint limits in terms of ranges of motion and identifies barriers therein
      where a person is required to attain a different posture. Examples include the
      workspaces of a typical forearm and a typical finger. The wrist's range of motion
      is used to illustrate the visualization of the progress in the functionality of a
      wrist undergoing rehabilitation.

PMID- 15513716
TI  - Standing at a kiosk: effects of key size and spacing on touch screen numeric
      keypad performance and user preference.
AB  - Touch screen input keys compete with other information for limited screen space.
      The present study estimated the smallest key size that would not degrade
      performance or user satisfaction. Twenty participants used finger touches to
      enter one, four or 10 digits in a numeric keypad displayed on a capacitive touch
      screen, while standing in front of a touch screen kiosk. Key size (10, 15, 20, 25
      mm square) and edge-to-edge key spacing (1, 3 mm) were factorially combined.
      Performance was evaluated with response time and errors, and user preferences
      were obtained. Spacing had no measurable effects. Entry times were longer and
      errors were higher for smaller key sizes, but no significant differences were
      found between key sizes of 20 and 25 mm. Participants also preferred 20 mm keys
      to smaller keys, and they were indifferent between 20 and 25 mm keys. Therefore,
      a key size of 20 mm was found to be sufficiently large for land-on key entry.

PMID- 15513717
TI  - Moisture accumulation in sleeping bags at - 7 degrees C and - 20 degrees C in
      relation to cover material and method of use.
AB  - Moisture accumulation in sleeping bags during extended periods of use is
      detrimental to thermal comfort of the sleeper, and in extreme cases may lead to
      sleep loss and hypothermia. As sub-zero temperatures were expected to affect
      vapour resistance of microporous membranes, the effect of using semipermeable and
      impermeable rain covers for sleeping bags on the accumulation of moisture in the
      bags during 6 days of use at - 7 degrees C and 5 days at - 20 degrees C were
      investigated. In addition, the routine of shaking off hoarfrost from the inside
      of the cover after the sleep period as a preventive measure for moisture
      accumulation was studied. Moisture accumulation (ranging from 92 to 800 grams)
      was found to be related to the vapour resistance of the materials used. The best
      semipermeable material gave the same moisture build-up as no cover at - 7 degrees
      C, though build-up increased substantially at - 20 degrees C. Shaking off the
      hoarfrost from the inside of the cover after each use was beneficial in
      preventing a high moisture build-up. It was concluded that semi-permeable cover
      materials reduce moisture accumulation in sleeping bags at moderate sub-zero
      temperatures, but in more extreme cold (- 20 degrees C) the benefits are reduced
      in comparison to routinely shaking frost from impermeable covers. Compared to
      fixed impermeable covers, the benefits of all semi-permeable covers are large.
      For long-term use without drying facilities, the differences observed do favour
      the semi-permeable covers above impermeable ones, even when regularly removing
      the hoarfrost from the inside in the latter.

PMID- 15513718
TI  - Predictors of whole-body vibration exposure experienced by highway transport
      truck operators.
AB  - Whole-body-vibration (WBV) exposure levels experienced by transport truck
      operators were investigated to determine whether operator's exposure exceeded the
      1997 International Standards Organization (ISO) 2631-1 WBV guidelines. A second
      purpose of the study was to determine which truck characteristics predicted the
      levels of WBV exposures experienced. The predictor variables selected based on
      previous literature and our transportation consultant group included road
      condition, truck type, driver experience, truck mileage and seat type. Tests were
      conducted on four major highways with 5 min random samples taken every 30 min of
      travel at speeds greater than or equal to 80 km/h (i.e. highway driving). Results
      indicated operators were not on average at increased risk of adverse health
      effects from daily exposures when compared to the ISO WBV guidelines. Significant
      regression models predicting the frequency-weighted RMS accelerations for the x
      (F((5,97)) = 8.63, p < 0.01), y (F((5,97)) = 7.74, p < 0.01), z (F((5,61)) =
      9.83, p < 0.01) axes and the vector sum of the orthogonal axes (F((5,61)) =
      13.89, p < 0.01) were observed. Road condition was a significant predictor (p <
      0.01) of the frequency-weighted RMS accelerations for all three axes and the
      vector sum of the axes, as was truck type (p < 0.01) for the z-axis and vector
      sum. Future research should explore the effects of seasonal driving, larger
      vehicle age differences, greater variety of seating and suspension systems and
      team driving situations.

PMID- 15513719
TI  - Apparent mass of small children: experimental measurements.
AB  - A test facility and protocol were developed for measuring the seated, vertical,
      whole-body vibration response of small children of less than 18 kg in mass over
      the frequency range from 1 to 45 Hz. The facility and protocol adhered to the
      human vibration testing guidelines of BS7085 and to current codes of ethics for
      research involving children. Additional procedures were also developed which are
      not currently defined in the guidelines, including the integral involvement of
      the parents and steps taken to maximize child happiness. Eight children were
      tested at amplitudes of 0.8 and 1.2 m/s(2) using band-limited, Gaussian, white
      noise acceleration signals defined over the frequency interval from 1 to 50 Hz.
      Driving point apparent mass modulus and phase curves were determined for all
      eight children at both test amplitudes. All results presented a single,
      principal, anti-resonance, and were similar to data reported for primates and for
      adult humans seated in an automotive posture which provided backrest support. The
      mean frequency of the apparent mass peak was 6.25 Hz for the small children, as
      compared to values between 6.5 - 8.5 Hz for small primates and values between 6.5
      - 8.6 Hz for adults seated with backrest support. The peak value of the mean,
      normalized, apparent mass was 1.54 for the children, which compares to values
      from 1.19 to 1.45 reported in the literature for small primates and 1.28 for
      adults seated with backrest support. ISO standard 5982, which specifies a mean,
      normalized, apparent mass modulus peak of 1.50 at a frequency of 4.0 Hz for
      adults seated without backrest support, provides significant differences.

PMID- 15513721
TI  - Augmentative and Alternative Communication (AAC) for adults with severe aphasia:
      where we stand and how we can go further.
AB  - PURPOSE: To review literature specific to the use of AAC with adults who have
      severe aphasia. METHOD: The authors reviewed studies involving AAC interventions
      for adults with severe aphasia. RESULTS: Published data support the use of aided
      and unaided AAC with adults with severe aphasia in controlled treatment contexts.
      Reported gains in communication typically have not generalized to everyday
      settings. CONCLUSIONS: The application of AAC with persons with severe aphasia
      must address factors potentially limiting treatment success outside of training
      environments.

PMID- 15513722
TI  - Evaluating parent use of functional communication training to replace and enhance
      prelinguistic behaviours in six children with developmental and physical
      disabilities.
AB  - PURPOSE: To evaluate parent use of functional communication training (FCT) to
      replace and enhance prelinguistic behaviours in six young children with
      developmental and physical disabilities. METHOD: Initially, the communicative
      functions of the children's prelinguistic behaviours were assessed by parent
      interviews. Three communication functions were identified for each child and
      intervention goals to replace or enhance the child's existing prelinguistic
      behaviours were developed in consultation with parents. After a baseline phase,
      parents received training on implementation of FCT. Intervention was staggered
      across the three communicative functions in a multiple-probe design. RESULTS:
      Intervention was associated with increases in the replacement communication
      behaviour. Treatment gains were generally maintained at the monthly follow-ups.
      CONCLUSION: The results suggest that parents can use FCT to enhance communication
      skills in children with developmental and physical disabilities.

PMID- 15513723
TI  - Conditional use of a request for assistance.
AB  - PURPOSE: To establish the conditional use of requests for assistance as an
      alternative to escape maintained challenging behaviour. METHOD: The study
      involved a 12-year-old boy with a behaviour disorder. Experiment 1 involved the
      implementation of a reversal design comparing the learner's performance during
      "easy" and "difficult" addition problems. Experiment 2 involved the
      implementation of a quasi-experimental design to establish the conditional use of
      requests for assistance. RESULTS: Conditional use of requests for assistance
      successfully competed with escape maintained challenging behaviour. CONCLUSIONS:
      Our results suggest that for a newly acquired response to be displayed
      conditionally, two events must occur. First, the individual must learn the skill
      that has been associated with requests for assistance. Secondly, the
      contingencies must be such that reinforcement value is greater for an independent
      response than for a response that involves a request for assistance.

PMID- 15513724
TI  - Communicative functioning in individuals with Angelman syndrome: a comparative
      study.
AB  - PURPOSE: To assess expressive communication in individuals with Angelman
      syndrome. METHOD: Communicative functioning of individuals with Angelman syndrome
      (AS) (n = 109) was compared with individuals with mixed etiologies (n = 117)
      using the Verbal Behaviour Assessment Scale (VerBAS). RESULTS: Within-group
      analyses of those with AS revealed that the communicative function of manding was
      significantly more developed than tacting and echoing, and that tacting was
      significantly more developed than echoing. Low mean total VerBAS-scores were
      found with individuals who had epilepsy and used anticonvulsant medication, and
      with those who had profound developmental disabilities. In the comparison group,
      the function of manding was significantly more developed than both tacting and
      echoing, while tacting did not differ from echoing. Between-groups analyses
      revealed that individuals with AS had significantly lower scores on tacting and
      echoing, but not on manding. CONCLUSION: The overall pattern of VerBAS scores for
      individuals with AS suggests a possible communicative phenotype.

PMID- 15513725
TI  - Facilitating communication in children with multiple disabilities: three case
      studies of girls with Rett syndrome.
AB  - PURPOSE: To investigate the effect of cueing on communicative responses of
      children with multiple disabilities in an educational setting. It was
      hypothesized that differences would exist in teacher interactional styles and the
      use of orienting cues would increase the communicative responses of the
      participants. METHOD: A naturalistic observation research method was employed in
      order to examine the interaction of three student-teacher dyads in three special
      schools. Three different activity types were videotaped from which interactions
      were coded and analysed. RESULTS: Multi-modal cueing facilitated communicative
      responses of children with Rett syndrome. However, increased communication
      opportunities provided by caregivers did not elicit increased responses from the
      girls. CONCLUSION: There is a difference in cueing by teachers in their
      interactions with children with multiple disabilities. Also, more frequent
      communicative interactions did not necessarily lead to increased student
      responses. It is suggested that amount and type of cueing may need to be
      considered to be effective in generating student responses. The small number of
      participants, however, means findings should be viewed cautiously and that more
      research is indicated.

PMID- 15513726
TI  - Effects of synthetic speech output in the learning of graphic symbols of varied
      iconicity.
AB  - PURPOSE: To examine the effects of additional auditory feedback from synthetic
      speech on the learning of high translucent symbols versus low translucent
      symbols. METHOD: Two adults with little or no functional speech and severe
      intellectual disabilities served as participants. A single-subject ABACA/ACABA
      design was used to study the relative effects of two treatments: symbol training
      in the presence and absence of synthetic speech output. RESULTS: The results
      clearly indicated that the two treatments, rather than extraneous variables were
      responsible for gains in the symbol learning. Both participants learned either
      more low translucent symbols or reached their maximum learning of low translucent
      symbols in the speech output condition. CONCLUSIONS: The results of this
      preliminary study replicate and extend the iconicity hypothesis to a new set of
      learning conditions involving speech output, and suggest that feedback from
      speech output may assist adults with profound intellectual disabilities in coding
      particularly those symbols whose association with their referent cannot be coded
      via their visual resemblance with the referent.

PMID- 15513727
TI  - Evaluating a computer system used as a microswitch for word utterances of persons
      with multiple disabilities.
AB  - PURPOSE: To assess the effectiveness of a computer system used as a microswitch
      for word utterances of two adults with multiple disabilities. The system combined
      a new control software programme with a commercially available speech recognition
      programme. METHOD: Nine word utterances were targeted for each participant. The
      participant's emission of those utterances triggered the occurrence of related
      (favourite) stimuli during the intervention and the post-intervention check.
      RESULTS: Intervention data showed that (1) the participants increased the
      frequencies of the target utterances and (2) the computer system recognized about
      80% of those utterances correctly, providing the participants with high levels of
      favourite stimulation. The post-intervention check showed comparable data with
      both participants. CONCLUSIONS: The computer system proved an adequate
      microswitch for word utterances. Based on this evidence, microswitch programmes
      could be extended beyond the use of conventional motor responses.

PMID- 15513728
TI  - Enabling a person with multiple disabilities and minimal motor behaviour to
      control environmental stimulation with chin movements.
AB  - PURPOSE: To assess whether a young man with multiple disabilities and minimal
      motor behaviour would learn to control environmental stimulation using chin
      movements and a mechanical microswitch. METHOD: The study was carried out
      according to an ABAB design in which A represented baseline and B intervention
      phases. The chin movements controlled the stimulation only during the
      intervention phases. A 2-month post-intervention check was conducted. RESULTS:
      The man increased the frequency of his chin movements, thus increasing the level
      of environmental stimulation, during the intervention phases. This performance
      was maintained at the post-intervention check. CONCLUSION: The use of chin
      movements is a practical strategy for enabling individuals with minimal motor
      movements to control environmental stimulation. Future research should examine
      whether similar types of movements may enable some individuals to control voice
      output communication devices.

PMID- 15513729
TI  - Effects of phonemic awareness instruction on the encoding skills of children with
      severe speech impairment.
AB  - PURPOSE: To examine the effects of phoneme-grapheme correspondence and phonemic
      awareness instruction on the encoding abilities of three pre-reading children
      with severe speech impairment (SSI). METHOD: Using a single subject multiple
      baseline design across behaviours and participants, children received phoneme
      grapheme awareness instruction followed by instruction in segmenting,
      manipulating, and encoding consonant-vowel-consonant (CVC) pseudowords. RESULTS:
      Generalization occurred to encoding of novel CVC pseudo- and real words for two
      of the three participants. CONCLUSIONS: Results suggest that phoneme-grapheme
      correspondence and phonemic awareness instruction is effective in developing
      encoding skills in children with SSI. Findings are consistent with those for
      other at-risk children.

PMID- 15513730
TI  - AAC and literacy.
AB  - PURPOSE: To review current research on the use of augmentative and alternative
      communication (AAC) for prompting literacy in children with special educational
      needs. METHOD: Research studies relevant to emergent literacy and AAC use are
      reviewed. Studies focused on acquisition of literacy across various populations
      of children with special needs are reviewed. RESULTS: Existing literature
      suggests that AAC may provide strategies and systems to compensate for
      impairments and disabilities of individuals with severe communication disorders.
      CONCLUSION: AAC may support literacy learning in children with special
      educational needs.

PMID- 15513731
TI  - Parent-child interaction: a comparison of parents' perceptions in three groups.
AB  - PURPOSE: To evaluate a children's version of the ICF that takes children's
      dependency on their parents and a developmental perspective into consideration.
      METHOD: This study explored how 91 parents perceived child participation in terms
      of parent/child immediate interaction, and desires for ideal interaction in
      relation to body impairments and activity limitations. Similarities and
      differences were investigated in three matched groups of families through
      questionnaires. Group 1 consisted of parents of children with profound multiple
      disabilities, Group 2 was developmentally matched and Group 3 was matched
      according to chronological age. RESULTS: The children with profound multiple
      disabilities expressed the same amount of emotions as the other groups, but they
      had difficulties expressing more complex emotions. Parents perceived the
      children's behaviour styles in a similar way in the three groups. There were
      significant differences in how the immediate interaction was perceived with
      parents to children of Group 1 perceiving difficulties in maintaining joint
      attention and directing attention. CONCLUSIONS: The results suggest that parental
      perceptions of the interaction with their children with profound multiple
      disabilities in the immediate setting to a certain extent are related to the body
      impairments of the children but not strongly to communicative skills /activity
      limitations. Thus, to focus communication intervention on participation and
      interaction, assessment and questions to parents have to be focused directly on
      these issues.

PMID- 15513732
TI  - Research directions in augmentative and alternative communication for preschool
      children.
AB  - PURPOSE: To review issues related to the use of augmentative systems with young
      children and present a case study of one child and family's experience with the
      System for Augmenting Language (SAL). METHOD: The case involved a preschool child
      with severe developmental delays who had little functional speech. Acquisition
      and use of graphic symbols on a speech-output communication device was studied in
      home and clinical settings. Language and communication behaviours of the child
      and his communication partners were observed and language assessment measures
      were collected. RESULTS: Child engagement state varied across the two settings
      with a stable profile seen in the therapy setting and a clear increase at home.
      Child communicative attempts increased following the introduction of the
      augmented system. Parents reported successful use of the SAL. CONCLUSION: SAL is
      a viable communication intervention approach for young children.

PMID- 15513733
TI  - Transferring AAC intervention to the home.
AB  - PURPOSE: To evaluate the acquisition of AAC skills during an initial clinical
      trial and assess subsequent transfer of the training to the home setting. METHOD:
      A 12-year-old male with autism was first seen in a clinical setting to establish
      the use of a voice-output communication device. After learning to use the device
      to request access to preferred objects in the clinical trial, the intervention
      was transferred to the home. Follow-up with the parent was conducted via e-mail
      and telephone. Videotapes were made of initial home-based sessions to enable
      evaluation of the participant's progress. RESULTS: The programme was successful
      in teaching the participant to use a portable AAC device to make requests during
      the clinical trial and then in two home-based activities. CONCLUSION: An initial
      clinical trial with follow-up support for parents may be an efficient method for
      beginning AAC intervention and transferring the training procedures to the home
      setting.

PMID- 15513734
TI  - Acquisition of graphic communication by a young girl without comprehension of
      spoken language.
AB  - PURPOSE: To describe a graphic-mode communication intervention involving a girl
      with intellectual impairment and autism who did not develop comprehension of
      spoken language. The aim was to teach graphic-mode vocabulary that reflected her
      interests, preferences, and the activities and routines of her daily life, by
      providing sufficient cues to the meanings of the graphic representations so that
      she would not need to comprehend spoken instructions. METHOD: An individual case
      study design was selected, including the use of written records, participant
      observation, and registration of the girl's graphic vocabulary and use of graphic
      signs and other communicative expressions. RESULTS: While the girl's
      comprehension (and hence use) of spoken language remained lacking over a 3-year
      period, she acquired an active use of over 80 photographs and pictograms.
      CONCLUSIONS: The girl was able to cope better with the cognitive and attentional
      requirements of graphic communication than those of spoken language and manual
      signs, which had been focused in earlier interventions. Her achievements
      demonstrate that it is possible for communication-impaired children to learn to
      use an augmentative and alternative communication system without speech
      comprehension, provided the intervention utilizes functional strategies and non
      language cues to the meaning of the graphic representations that are taught.

PMID- 15513735
TI  - Cell biology of virus entry: a review of the 4th International Frederick Meeting.

PMID- 15513736
TI  - Characterization of the caprine (Capra hircus) beta-2 integrin CD18-encoding cDNA
      and identification of mutations potentially responsible for the ruminant-specific
      virulence of Mannheimia haemolytica.
AB  - The leukocyte integrins play a critical role in a great number of cellular
      adhesive interactions during the immune response. We describe here the isolation
      and characterization of the caprine beta(2) (CD18) sub-unit, common to the
      leukocyte beta(2)-integrin family. The deduced 770-amino-acid sequence reveals a
      transmembrane protein with 80, 81, 83, 96 and 99% identity with its canine,
      murine, human, bovine and ovine homologues respectively. Analysis of CD18
      sequences emphasizes the functional importance of the beta(2) sub-unit I-like
      domain, and included metal ion-dependent adhesion site-like motif and confirms
      that of the cytoplasmic tail. Moreover, comparisons of ruminant versus non
      ruminant CD18 sequences allowed the identification of 16 potential mutation sites
      that could be held responsible for the unique virulence of Mannheimia haemolytica
      for ruminants. Mannheimiosis is known to be the major respiratory disease among
      ruminants, whereas it is not pathogenic for other mammals, an observation that
      has been attributed to a specific interaction between M. haemolytica leukotoxin
      and ruminants' CD18. Therefore, the data provided here offer the possibility to
      explore new avenues in studies based on the caprine model and provide key
      information for future studies aimed at elucidating the molecular mechanisms
      underlying the ruminant-specific virulence of M. haemolytica.

PMID- 15513737
TI  - Solution structure of the first and second transmembrane segments of the
      mitochondrial oxoglutarate carrier.
AB  - The structures of the first and the second transmembrane segment of the bovine
      mitochondrial oxoglutarate carrier (OGC) were studied by circular dichroism (CD)
      and nuclear magnetic resonance (NMR) spectroscopies. Peptides 21-46 and 78-108 of
      its primary sequence were synthesized and structurally characterized in membrane
      mimetic environments. CD data showed that at high concentrations of TFE (>50%)
      and SDS (>2%) both peptides assume alpha-helical structures, whereas in more
      hydrophilic environments only peptide 78-108 has a helical structure. (1)H-NMR
      spectra of the two peptides in TFE/water and SDS were fully assigned, and the
      secondary structures of the peptides were obtained from nuclear Overhauser
      effects, (3)J(alphaH-NH) coupling constants and alphaH chemical shifts. The three
      dimensional solution structures of the peptides in TFE/water were generated by
      distance geometry calculations. A well-defined alpha-helix was found in the
      region K24-V39 of peptide 21-46 and in the region A86-F106 of peptide 78-108. We
      cannot exclude that in intact OGC the extension of these helices is longer. The
      helix of peptide 21-46 is essentially hydrophobic, whereas that of peptide 78-108
      is predominantly hydrophilic.

PMID- 15513738
TI  - pH modulation of large conductance potassium channel from adrenal chromaffin
      granules.
AB  - We report here that large conductance K(+) selective channel in adrenal
      chromaffin granules is controlled by pH. We measured electrogenic influx of
      (86)Rb(+) into chromaffin granules prepared from bovine adrenal gland medulla.
      The (86)Rb(+) influx was inhibited by acidic pH. Purified chromaffin granule
      membranes were also fused with planar lipid bilayer. A potassium channel with
      conductance of 432+/-9 pS in symmetric 450 mM KCl was observed after
      reconstitution into lipid bilayer. The channel activity was unaffected by
      charybdotoxin, a blocker of the Ca(2+)-activated K(+) channel of large
      conductance. It was observed that acidification to pH 6.4 cis side of the
      membrane lowered the channel open probability and single channel conductance.
      Whereas only weak influence on the single channel current amplitude and open
      probability were observed upon lowering of the pH at the trans side. We conclude
      that a pH-sensitive large conductance potassium channel operates in the
      chromaffin granule membrane.

PMID- 15513739
TI  - On the mechanism of drug-induced acceleration of phospholipid translocation in
      the human erythrocyte membrane.
AB  - Small amphiphilic compounds (M(r)<200 Da) such as anaesthetics and hexane
      derivatives with different polar groups produced a concentration-dependent
      acceleration of the slow passive transbilayer movement of NBD-labelled
      phosphatidylcholine in the human erythrocyte membrane. Above a threshold
      concentration characteristic for each compound, the flip rate gradually increased
      at increasing concentrations in the medium. For compound concentrations required
      to produce a defined flip acceleration, corresponding membrane concentrations
      were estimated using reported octanol/water partition coefficients. The effective
      threshold membrane concentrations (50-150 mmol l(-1)) varied in the order:
      hexylamine>isoflurane=hexanoic acid>hexanol=chloroform>hexanethiol=1,1,2,2
      tetrachloroethane>chlorohexane. Apolar hexane, which mainly distributes in the
      apolar membrane core, was much less effective and supersaturating concentrations
      were required to enhance flip. Localization of the drug at the lipid-water
      interface seems to be required for flip acceleration. Such a localization may
      increase the lateral pressure in this region and the bilayer curvature stress
      with concomitant decrease of order and rigidity at the interface. This unspecific
      bilayer perturbation is proposed to enhance the probability of formation of
      hydrophobic defects in the bilayer, facilitating penetration of the polar head
      group of the phospholipid into the apolar membrane core.

PMID- 15513740
TI  - Purification and properties of the Escherichia coli nucleoside transporter NupG,
      a paradigm for a major facilitator transporter sub-family.
AB  - NupG from Escherichia coli is the archetype of a family of nucleoside
      transporters found in several eubacterial groups and has distant homologues in
      eukaryotes, including man. To facilitate investigation of its molecular
      mechanism, we developed methods for expressing an oligohistidine-tagged form of
      NupG both at high levels (>20% of the inner membrane protein) in E. coli and in
      Xenopus laevis oocytes. In E. coli recombinant NupG transported purine
      (adenosine) and pyrimidine (uridine) nucleosides with apparent K(m) values of
      approximately 20-30 microM and transport was energized primarily by the membrane
      potential component of the proton motive force. Competition experiments in E.
      coli and measurements of uptake in oocytes confirmed that NupG was a broad
      specificity transporter of purine and pyrimidine nucleosides. Importantly, using
      high-level expression in E. coli and magic-angle spinning cross-polarization
      solid-state nuclear magnetic resonance, we have for the first time been able
      directly to measure the binding of the permeant ([1'-(13)C]uridine) to the
      protein and to assess its relative mobility within the binding site, under non
      energized conditions. Purification of over-expressed NupG to near homogeneity by
      metal chelate affinity chromatography, with retention of transport function in
      reconstitution assays, was also achieved. Fourier transform infrared and circular
      dichroism spectroscopy provided further evidence that the purified protein
      retained its 3D conformation and was predominantly alpha-helical in nature,
      consistent with a proposed structure containing 12 transmembrane helices. These
      findings open the way to elucidating the molecular mechanism of transport in this
      key family of membrane transporters.

PMID- 15513741
TI  - BAEP dynamic estimation in case of endocochlear pathologies using a time delay
      correction method.
AB  - Extraction of Brainstem Auditory Evoked Potentials (BAEPs) from the
      electroencephalogram (EEG) is generally difficult when both BAEP and EEG are non
      stationary. In this paper we focus on the problem of BAEP non-stationarities, in
      particular those observed in some endocochlear pathologies assumed causing random
      delays of BAEPs due to an abnormal behaviour of the cochlea. The technique
      developed in this paper, called the Time Delay Correction (TDC) method, allows us
      to estimate the averaged BAEP by an optimal alignment of responses based on a
      correlation criterion. We demonstrate that the TDC method avoids wave smoothness,
      generally produced with the classical ensemble averaging method, especially in
      the case when the hypothesis of the time delay non-stationarity is verified. The
      TDC method is performed using simulated annealing (SA) algorithm, since the
      criterion to be optimized is nonlinear. Real signals recorded from pathological
      subjects are used to validate the model of non-stationarity.

PMID- 15513742
TI  - The relation between viable segments and left ventricular ejection fraction
      improvement.
AB  - For patients with coronary artery disease and left ventricular dysfunction who
      undergo revascularization, it is important to estimate the left ventricular
      ejection fraction (LVEF) improvement after revascularization, as this is a strong
      indicator of the long-term outcome. Identification of viable segments from
      echocardiography has been considered a predictive sign of LVEF improvement.
      However, a quantitative relation between segmental function recovery and global
      ejection fraction improvement has not been established. There is a clinical need
      to determine parameters that are predictive to LVEF improvement. A cylindrical
      left ventricular model is proposed to establish the relation between segmental
      myocardial function and LVEF based on a 12-segment echocardiograph model. Model
      results show that LVEF improvement is directly related to the contraction ratio
      in normal segments and a weighted sum of the number of viable segments that
      recover to normal or hypokinetic, which is equal to a weighted sum of the change
      in wall motion scores. This new combined parameter is a better predictor of the
      amount of LVEF improvement than the total number of viable segments or
      preoperative ejection fraction. The predictive value of the model was illustrated
      in a group of four patients with coronary artery disease who underwent
      revascularization.

PMID- 15513743
TI  - A portable hand-held device for quantifying and standardizing tremor assessment.
AB  - We describe the results of a hand-held device for quantifying tremor in the upper
      extremity. The specific aims of the study were to evaluate: (1) the reliability
      of the device to record tremor frequency and amplitude; (2) the relationship
      between observer ratings of tremor severity and spectral power derived from the
      instrument; (3) the effects of limb posture on tremor properties recorded by the
      instrument; and (4) whether scores from the instrument can discriminate types of
      tremor with sufficient accuracy to be of diagnostic value. Results from 242
      subjects with tremor showed significant effects of limb posture on tremor
      frequency detected by the device which could not be revealed using traditional
      observer severity ratings. Subjects with tremor associated with idiopathic
      Parkinson's disease were distinguished from patients with drug-induced
      parkinsonian tremor with 83% accuracy. These and other findings on instrument
      validity demonstrate that tremor assessment can be performed using standard
      quantitative procedures which overcome many of the limitations inherent in
      subjective observer ratings. The portability of this instrument, referred to as
      the Tremorometer, makes it a useful tool for multi-site collaborative studies in
      community settings.

PMID- 15513744
TI  - Sampling frequency of the RR interval time series for spectral analysis of heart
      rate variability.
AB  - Spectral analysis of heart rate variability (HRV) is an accepted method for
      assessment of cardiac autonomic function and its relationship to numerous
      disorders and diseases. Various non-parametric methods for HRV estimation have
      been developed and extensive literature on their respective properties is
      available. The RR interval time series can be seen as a series of non-uniformly
      spaced samples. To analyse the power spectra of this series using the discrete
      Fourier transform (DFT), we need to interpolate the series for obtaining
      uniformly spaced intervals. The selection of sampling period plays a critical
      role in obtaining the power spectra in terms of computational efficiency and
      accuracy. In this paper, we shall analyse the RR interval time series from
      selected subjects for different sampling frequencies to compare the error
      introduced in selected frequency-domain measures of HRV at a constant frequency
      resolution for a specific duration of electrocardiogram (ECG) data. It should be
      pointed out that, although many other error causes are possible in the frequency
      domain measures, our attention will be confined only to the performance
      comparison due to the different sampling frequencies. While the choice of RR
      interval sampling frequency (f(s)) is arbitrary, the sampling rate of RR interval
      series must be selected with due consideration to mean and minimum RR interval;
      f(s = )4 Hz was proposed for a majority of cases. This is an appropriate sampling
      rate for the study of autonomic regulation, since it enables us to compute
      reliable spectral estimates between dc and 1 Hz, which represents the frequency
      band within which the autonomic nervous system has significant response.
      Furthermore, resampled RR intervals are evenly spaced in time and are
      synchronized with the samples of the other physiologic signals, enabling cross
      spectral estimates with these signals.

PMID- 15513745
TI  - In vitro and in vivo properties of usnic acid encapsulated into PLGA
      microspheres.
AB  - Microparticles will probably play a promising role in the future of chemotherapy.
      These polymeric delivery systems are capable of maximizing the therapeutic
      activity while reducing side effects of anti-cancer agents. Usnic acid (UA) is a
      secondary metabolite produced by lichens, which exhibits an anti-tumour activity.
      In this study, PLGA-microspheres containing usnic acid from Cladonia substellata
      were prepared by the double emulsion method, with or without PEG as stabilizer.
      The morphology of the microspheres was examined by optical and scanning electron
      microscopy. The in vitro kinetic profile of usnic acid loaded-microspheres was
      carried out by dissolution testing. The usnic acid content was analysed by HPLC.
      The cytotoxicity of free and encapsulated usnic acid was evaluated against HEp-2
      cells using the MTT method. The anti-tumour assay was performed in mice against
      Sarcoma-180 tumour (UA 15 mg kg(-1) weight body/day) during 7 days. Animals were
      then sacrificed and tumour and organs were excised for histopathological
      analysis. Microspheres presented a smooth spherical surface with a mean diameter
      of 7.02 +/- 2.72 microm. The usnic acid encapsulation efficiency was
      approximately 100% (UA 10 mg 460 mg(-1) microspheres). A maximum release of 92%
      was achieved at the fifth day. The IC50 values for free and encapsulated usnic
      acid were 12 and 14 microg ml(-1), respectively. The encapsulation of usnic acid
      into microspheres promoted an increase of 21% in the tumour inhibition as
      compared with the free usnic acid treatment. In summary, usnic acid was
      efficiently encapsulated into PLGA-microspheres and the microencapsulation
      improved its anti-tumour activity.

PMID- 15513746
TI  - Glass encapsulation of flavours with chemically modified starch blends.
AB  - Carrier compositions based on blends of various octenylsuccinic acid anhydride
      (OSAN)-modified starches were utilized in the glass encapsulation of flavours by
      means of melt extrusion and spray drying. Dextrinized, acid and enzymatically
      hydrolysed OSAN starches were used in various combinations. Processing parameters
      were optimized for desirable physical chemical and functional properties of the
      encapsulating compositions. One key property in the optimization of the extrusion
      process was setting rate of the exiting melt into a glass. Glassy states of
      identical spray-dried and extruded compositions were characterized by MDSC for
      glass transition temperature(s), heat capacity change and enthalpy relaxation.
      Flavour retention, surface flavour, moisture, particle density and flavour
      particle size distribution were also measured and compared for the extruded and
      spray-dried compositions. In addition, elastic recovery and caking were evaluated
      for extruded compositions. The glass transition parameters were correlated
      directly or indirectly with most of the physical properties of encapsulating
      compositions, especially flavour retention, surface flavour and caking. In
      extruded compositions, two phases were revealed by the presence of two glass
      transitions, whereas spray-dried compositions showed only one broad glass
      transition.

PMID- 15513747
TI  - Effects of polymer, organic solvent and mixing strength on integrity of proteins
      and liposomes encapsulated in polymeric microspheres fabricated by the double
      emulsion process.
AB  - The double emulsion process has commonly been applied to encapsulate water
      soluble bioactive agents into polymeric microspheres. However, the integrity of
      many of these agents may be destroyed by the highly energetic procedures such as
      sonication that are routinely used to produce stable water-in-oil (w/o) emulsion.
      The aim of this research was to pursue the possibility of replacing the
      sonication by a mild emulsification procedure such as vortex mixing, with the use
      of certain materials to help to obtain stable w/o emulsion. The following
      materials were examined: poly(lactide-co-ethylene glycol) (PELA) as the polymer,
      ethyl acetate and acetone as the solvents, poly(vinyl alcohol) (PVA) and d-alpha
      tocopheryl polyethylene glycol 1000 succinate (Vitamin E TPGS) as the emulsifiers
      in w/o emulsion. The experimental results, with human serum albumin (HSA) as the
      encapsulated agent, showed that, when vortex mixing was used, these materials
      could significantly improve w/o emulsion stability and help to obtain
      satisfactory encapsulation effects, i.e. high encapsulation efficiency (EE) and
      low initial release burst. A delicate structure, i.e. liposomes, which is very
      sensitive to sonication, was then incorporated into microspheres by the 'modified
      double emulsion process'. It was found that the liposomes were intact and the
      encapsulation effects were good. Therefore, it can be concluded that the modified
      double emulsion process could be advantageous for the encapsulation of delicate
      substances.

PMID- 15513748
TI  - Preparation of hydrogel hollow particles for cell encapsulation by a method of
      polyester core degradation.
AB  - Implantation of encapsulated cells in particles of less than 1 mm (micro
      encapsulation) has been proposed as a cell synthesized bio-molecule delivery
      system. Encapsulation provides immuno-isolation, protecting foreign cells from
      host immune system while nutrients, oxygen and therapeutic products can diffuse
      freely across capsule walls. A new method is described for the synthesis of a new
      family of hollow microparticles for cell encapsulation. Unlike other micro
      encapsulation methods, encapsulation in those devices will take place after
      capsule synthesis, by micro-injection. The microcapsules were prepared by a three
      steps original procedure: first, synthesis of a core particle, followed by
      coating with a layer of epichlorohydrin cross-linked amylo-pectin gel and,
      finally, selective degradation of the core particle to create the cavity. Initial
      experiments make use of amylo-pectin cross-linked with trimetaphosphate as core
      particle material. However, selective degradation was difficult to achieve. In
      further essays, polyesters were used successfully for the preparation of core
      particles. Optimizations were carried out and the permeability and morphology of
      the hollow particles were investigated. The preliminary results show that the new
      method has the potential to become a standard procedure to obtain hydrogel hollow
      particles. Moreover, the permeability study seems to be in accordance with
      specifications for immuno-isolation.

PMID- 15513749
TI  - In vitro and in vivo evaluation of albumin-encapsulated primaquine diphosphate
      prepared by nebulization into heated oil.
AB  - Nebulization of an aqueous mixture of primaquine diphosphate and albumin into
      heated vegetable oil produces spherical particles with an average size of 6
      microm. The microparticles are relatively stabile in buffers of pH 7.2 and 4.5
      and completely degrade when exposed to proteolytic enzymes such as trypsin.
      Pharmacokinetic evaluation of the albumin-encapsulated primaquine diphosphate
      shows significantly higher levels in mouse liver tissue relative to free drug 2
      48 h post-IP administration. Higher AUC (2.8x), lower steady-state volume of
      distribution (10x) and slower half-life (2.5x) relative to an equivalent dose of
      free primaquine diphosphate suggest liver targeting and sustained release of the
      drug from the microparticles.

PMID- 15513750
TI  - Nifedipine encapsulated core-shell type nanoparticles based on poly(gamma-benzyl
      L-glutamate)/poly(ethylene glycol) diblock copolymers.
AB  - The diblock copolymers based on PBLG and PEO (GE) were synthesized and
      characterized. Nanoparticles showed spherical shape from the observations of TEM
      and approved core-shell structure. Drug contents were increased with use of
      higher initial drug concentration and higher Mw of GE. Nifedipine (NFD) release
      rate was slower in longer PBLG chain length and higher NFD contents than short
      PBLG chain length and lower drug contents of NFD due to the hydrophobic
      interaction between PBLG domain and NFD.

PMID- 15513753
TI  - Literature alerts.

PMID- 15513751
TI  - Slow-cooling protocols for microcapsule cryopreservation.
AB  - The relatively large size (300-400 microm) and fragile semi-permeable membrane of
      microcapsules makes them particularly prone to cryodamage. This study
      investigated slow-cooling protocols for the cryopreservation of microcapsules.
      Instead of a programmable freezing-machine, slow cooling was carried out directly
      within a -80 degrees C refrigerator. A range of increasing cryoprotectant (DMSO
      and EG) concentrations with slow cooling was investigated. The results showed
      that 2.8 M (20% v/v) DMSO and 2.7 M (15% v/v) EG were optimal for microcapsule
      cryopreservation, resulting in approximately 55-60% of the microcapsules
      remaining intact, with a relatively high post-thaw cell viability of 80-85%. Post
      thaw cell viability and microcapsule integrity were consistently higher at
      equivalent molarities of DMSO compared to EG. Hence, all subsequent studies
      utilized only DMSO. Post-thaw cell viability upon slow cooling with 2.8 M (20%
      v/v) DMSO was significantly improved in the presence of 0.25 M sucrose (> 95%),
      but there was no enhancement in microcapsule integrity. Neither post-thaw cell
      viability nor microcapsule integrity was improved with multi-step exposure and
      removal of sucrose, compared to a single-step protocol. There was also no
      improvement in either post-thaw cell viability or microcapsule integrity in the
      presence of 20% (w/v) Ficoll. Hence, the optimal condition for microcapsule
      cryopreservation by slow-cooling is with 2.8 M (20% v/v) DMSO and 0.25 M sucrose.

PMID- 15513756
TI  - Ca-alginate microspheres encapsulated in chitosan beads.
AB  - Chitosan beads (CBs) incorporating Ca-alginate microspheres (CAMs), containing a
      drug, were prepared as an oral sustained delivery system. Stable and monodisperse
      Ca-alginate microspheres loaded with drug were obtained by a membrane
      emulsification method. The Ca-alginate microspheres were encapsulated in chitosan
      beads by the ionotropic gelation method with a polyelectrolyte complex reaction
      between two oppositely charged polyions. The surface and internal characteristics
      of the beads were improved by ionic cross-linking in tripolyphosphate (TPP)
      solution adjusted to pH 5.0. The release experiments were performed using
      lidocaine.HCl (cationic drug) and sodium salicylate (anionic drug) as model
      drugs. Initial release of drugs depended on the degree of swelling. Ca-alginate
      microspheres encapsulated in chitosan beads were superior to both drug-loaded CBs
      and CAMs beads for sustained release because they had a three-layer composition;
      a calcium alginate core bounded by an inter-phasic chitosan-alginate membrane,
      which itself was surrounded by a layer of chitosan-TPP.

PMID- 15513757
TI  - Nanoparticle-coated microparticles: preparation and characterization.
AB  - The objective of the present work was to design and prepare new nanoparticle
      coated drug-loaded inorganic microparticles by spray-drying using diclofenac as
      drug model. Previous works presented the process to dry drug-loaded polymeric
      nanoparticles using silicon dioxide as adjuvant, otherwise in the present
      proposition the drug is associated with the silicon dioxide and unloaded
      polymeric nanocapsule or nanosphere suspensions were used as organic coating.
      Eudragit S100 was chosen because of its gastric resistance. The potential
      application of polymeric colloidal suspensions as nanocoating for microparticles
      were evaluated in terms of process yields, encapsulation efficiencies,
      morphologic analyses and in vitro drug release profiles in buffered media (pH
      1.2; 5.0 and 7.4). The results showed the technological feasibility of preparing
      controlled nanoparticle-coated drug-loaded inorganic microparticles. When the
      diclofenac was employed as a hydrophilic model, in this salt form, the powders
      prepared in two steps (core previously prepared) showed an adequate
      gastroresistance by the use of Eudragit S100. The use of diclofenac as a
      hydrophobic model (acid form) conducted to powders presenting good
      gastroresistance when the nanocapsules and triacetin were employed.

PMID- 15513758
TI  - Adsorption and recovery of Cu (II) with polysulphone microcapsules containing
      chitosan gel.
AB  - Polysulphone (PSF) microcapsules (PSF-CTS) containing chitosan gel with higher
      mechanical stability and anti-biodegradability were prepared using a novel
      surface coating method. The thickness and microstructures of the polysulphone
      coating layer were analysed by SEM. The experiments to examine the mechanical
      improvement of the encapsulated gel beads were carried out. The adsorption for
      Cu2+ and regeneration properties of unencapsulated and encapsulated gel beads
      were also tested. The results showed that the mechanical strength of the
      encapsulated gel beads was significantly enhanced. However, this improvement led
      to a decrease of the adsorption kinetics due to the increase of the mass transfer
      resistance. The potentially available methods are suggested to reduce mass
      transport resistance through the PSF coating layer.

PMID- 15513759
TI  - Release characteristics of a model plasmid DNA encapsulated in biodegradable
      poly(ethylene glycol fumarate)/acrylamide hydrogel microspheres.
AB  - Biodegradable hydrogel microspheres were synthesized by free radical suspension
      copolymerization of poly(ethylene glycol fumarate) macromer with bisacrylamide
      (PEGF/PAM). The acidic initiator ammonium persulphate in combination with the
      basic accelerator, N,N,N',N'-tetramethyethylenediamine, were used to form the
      PEGF/PAM hydrogel at a neutral pH. The equilibrium water content of the
      microspheres was greater than 90% w/w. A model double stranded plasmid DNA
      (dsDNA) coding for the enhanced green fluorescence protein (pEGFP) gene was
      encapsulated in the hydrogel and the effect of loading and water content before
      swelling on release kinetics was investigated. Fluorescent confocal microscopy
      demonstrated that the encapsulated dsDNA was in the biologically active double
      stranded configuration. The highest loading of 0.81 mg ml(-1) resulted in the
      best encapsulation efficiency of 95%. For that loading, 6% of the dsDNA was
      released in 25 days at a rate of 16 ng ml(-1). The highest water content of 70%
      resulted in the highest burst release of 27% and 14% of the dsDNA was released in
      25 days at a rate of 30 ng ml(-1). For elucidating the release mechanism, the
      network mesh size was compared with the radius of gyration (Rg) of the dsDNA
      plasmid. The mesh size was 7 nm, which was less than Rg of the dsDNA (31 nm) but
      greater than the chain diameter of 1.1 nm. Since the mesh size was less than Rg,
      the release mechanism was by reptation of the segments of dsDNA within the tube
      formed by the network chains between crosslinks. These results indicate that the
      hydrogel mesh size and the size of the plasmid control the release mechanism.

PMID- 15513760
TI  - Preparation of chitosan microspheres using membrane emulsification and its size
      modelling.
AB  - The chitosan microspheres were prepared by a membrane emulsification method with
      variations of the N2 gas pressure and the chitosan concentration. The pressure of
      N2 gas was varied within the range from 0.2 x 10(5) to 0.8 x 10(5) Pa at chitosan
      concentration 1.5 wt%. In addition, the concentration of chitosan was varied
      between 0.5 approximately 2.0 wt% at 0.4 x 10(5) Pa of N2 gas pressure. Using
      this method, it is possible to prepare stable emulsions with a very narrow
      droplet size distribution in comparison with conventional methods. The average
      size of the microspheres was dependent on the N2 gas pressure and the
      concentration, that is it was increased with the pressure and the concentration.
      The modelling of the size for the microspheres according to the concentration was
      carried out using Macleod's relation and Parkins & Brown equation. The former
      shows the relationship between density and surface tension and the latter
      demonstrates the correlation between the volume of the microspheres and the
      interfacial tension. The modelling results were in good agreement with the
      experimental data to predict the microspheres size with the variation of
      concentration.

PMID- 15513761
TI  - Encapsulation of insulin-cyclodextrin complex in PLGA microspheres: a new
      approach for prolonged pulmonary insulin delivery.
AB  - The insulin administration by pulmonary route has been investigated in the last
      years with good perspectives as alternative for parenteral administration.
      However, it has been reported that insulin absorption after pulmonary
      administration is limited by various factors. Moreover, in the related studies
      one daily injection of long-acting insulin was necessary for a correct glycemic
      control. To abolish the insulin injection, the present study aimed to develop a
      new formulation for prolonged pulmonary insulin delivery based on the
      encapsulation of an insulin:dimethyl-beta-cyclodextrin (INS:DM-beta-CD) complex
      into PLGA microspheres. The molar ratio of insulin/cyclodextrin in the complex
      was equal to 1:5. The particles were obtained by the w/o/w solvent evaporation
      method. The inner aqueous phase of the w/o/w multiple emulsion contained the
      INS:DM-beta-CD complex. The characteristics of the INS:DM-beta-CD complex
      obtained were assessed by 1H-NMR spectroscopy and Circular Dichroism study. The
      average diameter of the microspheres prepared, evaluated by laser diffractometry,
      was 2.53 +/- 1.8 microm and the percentage of insulin loading was 14.76 +/- 1.1.
      The hypoglycemic response after intratracheal administration (3.0 I.U. kg(-1)) of
      INS:DM-beta-CD complex-loaded microspheres to diabetic rats indicated an
      efficient and prolonged release of the hormone compared with others insulin
      formulations essayed.

PMID- 15513764
TI  - Literature alerts.

PMID- 15513762
TI  - New approaches to the visualization, quantification and explanation of acid
      induced water loss from Ca-alginate hydrogel beads.
AB  - The water loss of Ca-alginate hydrogels at pHs below 4.0 was visualized with
      1HNMR-imaging by covering a single alginate bead with cyclohexane-d12 in a
      specially equipped NMR-tube and adding propionic acid at defined concentrations.
      The exact amount of water expelled from the beads was calculated from their
      weight loss and correlated with the acid concentrations and pHs within the
      hydrogel matrix. The maximum water loss of 52% (w/w) occurred at pH 1.0, while
      only 5% (w/w) of the initial water content were lost at pH 3.6. The analysis of
      the water collected from several alginate beads for Ca2+ -ions and free
      polysaccharides led to the assumption that, due to the acid-induced protonation
      of the carboxyl functions, the ionotropic network is gradually converted to an
      alginic acid gel structured by H-bonds. This contradicts existing theories
      explaining the pH-induced water loss by a lower solubility of the alginate chains
      and decreased repulsion between protonated carboxyl functions, but explains
      previously reported pH-dependent alterations of mass transport and drug retention
      of Ca-alginate gels. Thus, the presented experiments enable a more precise and
      complete view of the acid-induced process within Ca-alginate hydrogels. The
      transfer to the characterization of other hydrogels is possible and should be
      advantageous, especially if a calibration of the NMR-measurement could be
      achieved.

PMID- 15513766
TI  - Editorial: putting a new face on paediatric rehabilitation.

PMID- 15513767
TI  - Interventions for post-traumatic stress disorder in children and adolescents.
AB  - Clinical features, epidemiology and aetiology of post-traumatic stress disorder
      (PTSD) are outlined. Treatment outcome studies involving children with PTSD who
      have survived traumatic accidents, natural disasters and child sexual abuse are
      reviewed. An evidence-based assessment and treatment protocol is outlined for
      children and adolescents with PTSD. Key components of effective treatment are
      psycho-education about trauma reactions, sustained exposure to trauma-related
      cues and memories until habituation occurs, coping skills training for children
      to help them manage anxiety and parent training to equip parents with the skills
      to help them facilitate their children's recovery.

PMID- 15513768
TI  - Horticultural therapy: the 'healing garden'and gardening in rehabilitation
      measures at Danderyd Hospital Rehabilitation Clinic, Sweden.
AB  - OBJECTIVES: Objectives were to review the literature on horticultural therapy and
      describe the Danderyd Hospital Horticultural Therapy Garden and its associated
      horticultural therapy programme. DESIGN: The literature review is based on the
      search words 'gardening', 'healing garden' and 'horticultural therapy'. The
      description is based on the second author's personal knowledge and popular
      scientific articles initiated by her. The material has been integrated with
      acknowledged occupational therapy literature. SETTING: The setting was the
      Danderyd Hospital Rehabilitation Clinic, Sweden, Horticultural Therapy Garden.
      PARTICIPANTS: Forty-six patients with brain damage participated in group
      horticultural therapy. RESULTS: Horticulture therapy included the following
      forms: imagining nature, viewing nature, visiting a hospital healing garden and,
      most important, actual gardening. It was expected to influence healing, alleviate
      stress, increase well-being and promote participation in social life and re
      employment for people with mental or physical illness. The Horticultural Therapy
      Garden was described regarding the design of the outdoor environment, adaptations
      of garden tools, cultivation methods and plant material. This therapy programme
      for mediating mental healing, recreation, social interaction, sensory
      stimulation, cognitive re-organization and training of sensory motor function is
      outlined and pre-vocational skills and the teaching of ergonomical body positions
      are assessed. CONCLUSION: This study gives a broad historic survey and a
      systematic description of horticultural therapy with emphasis on its use in
      rehabilitation following brain damage. Horticulture therapy mediates emotional,
      cognitive and/or sensory motor functional improvement, increased social
      participation, health, well-being and life satisfaction. However, the
      effectiveness, especially of the interacting and acting forms, needs
      investigation.

PMID- 15513769
TI  - Violence is not necessary to produce subdural and retinal haemorrhage: a reply to
      Punt et al.
AB  - In this article we reply to the recent critique by Punt et al. in Pediatric
      Rehabilitation. Our hypothesis about the pathogenesis of intracranial bleeding in
      infants has three important implications. First, in the case of an infant with a
      swollen brain, subdural and retinal haemorrhage but no objective evidence of
      trauma, the findings by themselves are not certain evidence of abuse; second,
      violence is not necessary to produce subdural and retinal haemorrhage; and
      lastly, non-traumatic events producing apnoea with a catastrophic rise in
      intracranial pressure could produce a clinical picture identical to that seen in
      trauma.

PMID- 15513770
TI  - International perspectives on paediatric rehabilitation--Australia.
AB  - The rehabilitation of children with physical and acquired cognitive disability in
      Australia is described using four illustrative scenarios: an innovative programme
      for children with acquired brain injury; spasticity management in children with
      Cerebral Palsy; the training of medical consultants in paediatric rehabilitation;
      and professional development improvements.

PMID- 15513787
TI  - HIV/AIDS: The prioritization of prevention.

PMID- 15513789
TI  - Seropositive individuals willingness to communicate, self-efficacy, and
      assertiveness prior to HIV infection.
AB  - The purpose of this study was to examine possible communication similarities
      between human immunodeficiency virus (HIV) positive and HIV negative individuals.
      Forty HIV positive heterosexuals, who were infected through heterosexual sex,
      completed an on-line questionnaire to assess their safer sexual communication,
      willingness to communicate, condom self-efficacy, and assertiveness prior to HIV
      infection. Results indicate that prior to infection, HIV positive heterosexuals
      reported having similar safer sexual communication behaviors to those not
      infected with the virus. Participants in this study reported high levels of
      willingness to engage in safer sex communication, but low levels of actual
      communication. Further, results reveal that participants who engaged more often
      in safer sex communication were more likely to use condoms. Additionally,
      participants reported high levels of condom self-efficacy and moderate levels of
      assertiveness; both variables positively correlated with condom use. Finally,
      participants reported that they believed they did not need to discuss using
      condoms because they were not at risk. Previous safer sexual communication
      research reveals HIV negative individuals reported engaging in the same behaviors
      and holding the same beliefs reported by seropositive individuals. Hence,
      discussion of the importance of safer sexual communication and the utility of
      personalization to increase the communication of HIV negative individuals is
      explored.

PMID- 15513788
TI  - National Immunization Information Hotline: Calls concerning adverse events, 1998
      2000.
AB  - Data from the National Immunization Information Hotline (NIIH) concerning vaccine
      adverse event inquiries were analyzed from 1998 to 2000 (total n = 23,841 [public
      n = 14,330; health care professionals n = 9,511]). Approximately 20% of calls
      from the public from 1998 to 2000 concerned vaccine adverse events. These calls
      increased 199.5% from 1998 (n = 422) to 1999 (n = 1,264), then declined 12.4%
      from 1999 to 2000 (n = 1,107). A Lexus Nexus search showed that the number of
      news stories mentioning vaccine safety showed a similar pattern. Women were more
      likely to call the NIIH concerning vaccine adverse events than men, and persons
      40-59 years old and persons 60 years old and over were less likely to call about
      vaccine adverse events than those 20-39 years. The parallel trends in news
      stories mentioning vaccine safety and calls to the NIIH concerning adverse events
      suggests that news stories may stimulate questions about vaccine safety.
      Understanding that news stories may elicit questions about vaccine adverse events
      and examining the characteristics of persons who ask vaccine adverse event
      questions may guide future informational interventions toward those most in need.

PMID- 15513790
TI  - Social imagery, tobacco independence, and the truthsm campaign.
AB  - OBJECTIVES: This study investigated relationships among exposure to the truthsm
      campaign, differences in social imagery about not smoking and related measures,
      and smoking behavior. We asked, "How does truthsm work? Through what
      psychological mechanisms does it affect smoking behavior?" We developed a
      framework to explain how receptivity to truthsm ads might influence youth
      cognitive states and subsequent effects on progression to established smoking.
      The main hypotheses were that social imagery about not smoking and related
      beliefs and attitudes about tobacco use mediate the relationship between truthsm
      exposure and smoking status. METHODS: The study was based on data from the Legacy
      Media Tracking Survey (LMTS), waves I-III, which were conducted at three time
      points from 1999 through 2001. A nationally representative sample of 20,058
      respondents aged 12-24 from the three time points was used in the analysis. We
      developed a structural equation model (SEM) based on constructs drawn from the
      LMTS. We investigated the model and tested our hypotheses about the psychological
      and behavioral effects of campaign exposure. RESULTS: We tested our constructs
      and model using a two-stage structural equation modeling approach. We first
      conducted a confirmatory factor analysis (CFA) to test the measurement model. Our
      model achieved satisfactory fit, and we conducted the SEM to test our hypotheses.
      We found that social imagery and perceived tobacco independence mediate the
      relationship between truthsm exposure and smoking status. We found meaningful
      differences between paths for segmented samples based on age, gender, and
      race/ethnicity subgroups and over time. CONCLUSIONS: The truthsm campaign
      operates through individuals'sense of tobacco independence and social imagery
      about not smoking. This study indicates that the campaign's strategy has worked
      as predicted and represents an effective model for social marketing to change
      youth risk behaviors. Future studies should further investigate subgroup
      differences in campaign reactions and utilize contextual information about the
      truthsm campaign's evolution to explain changes in reactions over time.

PMID- 15513791
TI  - The Health Information National Trends Survey (HINTS): development, design, and
      dissemination.
AB  - Little is known about access, sources, and trust of cancer-related information,
      or factors that facilitate or hinder communication on a population-wide basis.
      Through a careful developmental process involving extensive input from many
      individuals and organizations, the National Cancer Institute (NCI) developed the
      Health Information National Trends Survey (HINTS) to help fill this gap. This
      nationally representative telephone survey of 6,369 persons aged > or = 18 years
      among the general population was first conducted in 2002-2003, and will be
      repeated biennially depending on availability of funding. The purpose of creating
      a population survey to be repeated on a cyclical basis is to track trends in the
      public's rapidly changing use of new communication technologies while charting
      progress in meeting health communication goals in terms of the public's
      knowledge, attitudes, and behaviors. The HINTS survey instrument was built upon
      extant models of health communication and behavior change, taking into account
      the rapidly changing communication environment. Questions in the survey were
      drawn from an overall theoretical framework that juxtaposed the"push" aspects of
      traditional broadcast media against the"pull" aspects of new media. HINTS data
      will be made widely available for researchers and practitioners; it will help
      further research in health communication and health promotion and provide useful
      information for programs, policies, and practices in a variety of settings.

PMID- 15513792
TI  - Toward reducing youth exposure to tobacco messages: examining the breadth of
      brand and nonbrand communications.
AB  - Young people cannot escape prosmoking messages in today's society. From magazine
      advertisements to billboards to promotional products to storefronts, the
      pervasive landscape of tobacco-related communications is unavoidable. Despite
      increased restrictions on tobacco advertising and promotion in recent decades,
      including the 1998 Master Settlement Agreement (MSA), tobacco companies continue
      to employ an extensive array of marketing communications practices that can reach
      youth. Moreover, minors encounter tobacco messages not only from branded sources
      (those paid for by the tobacco firms), but also through nonbranded sources, such
      as smoking portrayals on television and in films and prosmoking websites. In this
      article, we critically examine the myriad and far-reaching tobacco messages that
      young people face. Although tobacco company marketing that can reach minors has
      undergone much research and public scrutiny, the combined impact of those
      messages along with nonbrand messages that positively portray smoking has
      received much less attention. Since all messages communicate, not just branded
      ones, it is important to examine the breadth of tobacco communications to which
      young people are exposed. We close by offering recommendations both for reducing
      youth exposure to protobacco communications and enhancing anti-youth-smoking
      efforts.

PMID- 15513798
TI  - Home alone: the experience of women with type 2 diabetes who are new to intensive
      control.
AB  - Using an inductive interpretive approach we examined the early experiences of
      women learning intensive self-management of type 2 diabetes. The women expressed
      feelings of being very much "home alone" during their initial self-management
      experience, in spite of having requisite knowledge and skills from completing a
      state-of-the-art multidisciplinary diabetes educational program. Invariably,
      engagement in the self-management process resulted in strong emotional responses,
      self-blame, and negative characterizations of self. Conditions associated with
      ways of being engaged in intensive self-management are described and provide
      practitioners with needed personal and contextual information to inform clinical
      care.

PMID- 15513799
TI  - Midlife women's narratives of living alone.
AB  - Women who live alone in the United States maintain connectedness in ways that are
      not fully understood. The purposes of this study were to (1) describe midlife
      women's definitions of themselves and how these are related to living alone; (2)
      identify the role of connections in relation to self; and (3) describe how self
      definition is related to well-being. Van Manen's interpretive phenomenology and
      Riessmann's method of narrative analysis were used to examine the role of
      connections and well-being. Living alone was a core component of self. Outside
      connections supported the women's well-being. Women's future concerns included
      disability and financial viability. Directions for further study include
      examining the concepts of mattering and belonging in relation to women's
      emotional health.

PMID- 15513800
TI  - Risk factors for coronary artery disease (CAD) in Lebanese-Armenian women.
AB  - Coronary artery disease (CAD) is the leading cause of death among women over 50
      years of age. Preventive measures through lifestyle modification and management
      of CAD risk factors have contributed to a decrease in mortality from heart
      disease. The purpose of this article is to assess risk factors for CAD among the
      population of Lebanese-Armenian women, so that appropriate intervention
      strategies for risk reduction could be planned and implemented. A descriptive
      study to explore risk factors for CAD was conducted in a convenience sample of 83
      women who attended a series of panel discussions about risk factors for CAD. Data
      collection was done using structured interviews and clinical/laboratory studies.
      Analysis of data was done using frequency distributions. The results indicated
      that a significant proportion of the sample manifested risk factors for CAD
      including age, menopausal status, hypertension, hypercholesterolemia, high levels
      of low-density lipoproteins (LDL), low levels of high-density lipoproteins (HDL),
      and being overweight. In addition, hypertension was associated positively with
      age, total cholesterol, LDL and triglyceride levels, lack of physical activity,
      propensity to anger, and family history of hypertension. The findings suggest the
      need for further research and health risk reduction programs.

PMID- 15513801
TI  - The meaning of health: perspectives of Anglo and Latino older women.
AB  - This qualitative study, utilizing the dimensional analysis approach, was
      conducted to generate a substantive theory about the description and meaning of
      functional health from the perspectives of older Anglo and Latino women. Through
      focus group interviews with older Anglo and Latino women and data analysis, the
      investigators learned that the women's perceptions of functional health were
      vastly different. As planners and providers, we usually are trained in a health
      culture that is predominantly based on White, middle-class values. This
      ethnocentrism can act as a barrier leading us to disregard the notion that
      concepts such as health are not universally perceived. Findings from this study
      may enable us to achieve a closer approximation of the real experiences of our
      clients and to sensitize us to different world views.

PMID- 15513805
TI  - Anger and violence.

PMID- 15513806
TI  - Muslim culture and female self-immolation: implications for global women's health
      research and practice.
AB  - Self-immolation among young Muslim women in parts of the Middle East and Central
      Asia increasingly is becoming a cause of death and disability. Very little is
      known about this phenomenon. Thus, in this article we (1) examine, from the
      perspective of Muslim culture, the phenomenon of self-immolation among young
      Islamic women in the Muslim countries of Central Asia and the Middle East; (2)
      describe current international activities regarding Islamic female self
      immolation; and (3) discuss the implications of Islamic female self-immolation
      for global women's heath research and practice.

PMID- 15513807
TI  - Restorative health: lessening the impact of previous abuse and violence in the
      lives of vulnerable girls.
AB  - "Restorative health" is the idea that those who have been denied access to the
      social determinants of health, particularly as young children, should have the
      right to restoration of healthy functioning. In interviewing a group of
      vulnerable young women, ranging in age from 15 to 22, we discovered how they
      experience the link between health and justice in their lives. Participants were
      living on the street, in extreme poverty, or both. Traumatic early childhood
      events continued to affect their ability to function healthy. We conclude and
      suggest that certain rights-based principles need to ground the development of
      interventions with this group.

PMID- 15513808
TI  - What's the use in getting mad? Anger and instrumentality in women's
      relationships.
AB  - In two studies, we examined women's anger expression and its instrumental
      function in relationships by addressing the following questions: What is the
      relationship between women's self-reports of instrumentality and their perceived
      styles of anger expression? In what ways and situations do women see their anger
      expression as instrumental or goal enhancing? In Study I, we expected that
      women's perceived styles of anger expression would be positively related to
      instrumentality, as measured with the Personal Attributes Questionnaire (PAQ;
      Spence, Helmreich, & Stapp, JSAS Catalog of Selected Documents in Psychology, 4,
      43, 1974). Although our hypothesis was not supported, a positive relationship did
      emerge between assertiveness and instrumentality, as predicted. In Study II, we
      conducted three focus group discussions to elucidate women's experiences of anger
      and to provide clarification for the results of Study I. We identified group
      themes related to when women experienced their anger expression as instrumental
      as well as when women perceived themselves as noninstrumental in anger-arousing
      situations. In their narratives, women explained how they make decisions about
      expressing their anger based on relationship concerns.

PMID- 15513809
TI  - Women behind bars: could neurobiological correlates of past physical and sexual
      abuse contribute to criminal behavior?
AB  - Trauma, especially physical and sexual abuse inflicted by others, is often part
      of the personal histories of female prison inmates. These traumatic events have
      also been associated with neuropsychiatric conditions commonly found in female
      inmate populations. The purpose of this article is to provide a review of the
      literature and research findings about physical and sexual abuse perpetrated
      against female prison inmates predating their crimes, the neurobiological
      correlates, and related factors that could have contributed to criminal
      behaviors. This information is critical for abuse and crime prevention and
      rehabilitation of female victims who have become criminal offenders.

PMID- 15513810
TI  - It's not because I'm fat: perceived overweight and anger avoidance in marriage.
AB  - Employed married Israeli women responded to questions about their perceived
      weight, their husbands' evaluation of their appearance, and their expression of
      anger in marriage. Our data, based on 125 questionnaires and five in-depth
      interviews, supports the possibility that women who perceive themselves as
      overweight, that is, "fail" to live up to the standards of female beauty in
      society, often suppress their anger and express it in limited areas. Our findings
      suggest that women who have not been able to resist the appearance-directed
      normative imperative in the constitution of their feminine self have to work
      harder to meet gender norms that require "emotion work" in the form of anger
      avoidance.

PMID- 15513811
TI  - Who me, angry? Patterns of anger diversion in women.
AB  - Researchers suggest that women's experience of anger is very complex and may not
      be accounted for by existing anger models. The current study was an attempt to
      clarify a model of women's anger proposed by Cox, Stabb, and Bruckner in Women's
      Anger: Clinical and Developmental Perspectives, 1999. Anger diversion focuses on
      women's attempts to bypass anger awareness, to use indirect means to cope with
      anger, or both. A sample of predominantly college and graduate student women (N =
      514) completed a vignette questionnaire assessing diversionary anger styles as
      well as instruments evaluating symptoms, anger behaviors, emotional expression,
      and tendencies to respond in socially desirable ways. The results of the study
      partially support Cox and colleagues' model, particularly in distinguishing
      between diverting anger and expressing anger assertively. We found that women who
      divert anger are more vulnerable to symptoms such as depression, anxiety, and
      somatization than are women who use an assertive approach to coping with anger.

PMID- 15513813
TI  - An analysis of the association between respiratory symptoms in subjects with
      asthma and daily air pollution in Spokane, Washington.
AB  - The association between respiratory symptoms and ambient levels of particulate
      matter (PM) air pollution has been the focus of several panel studies. The
      majority of studies focused only on PM10, were conducted for relatively short
      periods, reported peak flow data, and involved children with asthma. The goal of
      our study was to evaluate the effect of particulate matter of various size
      fractions (PM10, PM2.5, PM1.0, and PM coarse fraction) on respiratory symptoms in
      both adults and children with asthma monitored over many months. Daily diary data
      on respiratory symptoms and medication use were collected. Air pollution data
      were collected by the local air agency and Washington State University. Data were
      collected in Spokane, WA, a semiarid city with diverse sources of particulate
      matter, including motor vehicles, woodstoves, agricultural burning, resuspended
      road dust, and dust storms. Sixteen adults and nine children living in Spokane
      participated in the study. The majority of adult subjects participated for over 1
      yr and the children were studied for over 8 mo. In the children, we found a
      strong association between cough and PM10, PM2.5, PM coarse fraction, and PM1.0(p
      < .05). Sputum production and runny nose were associated with PM10and coarse
      fraction. However, no association was found between the presence of any
      respiratory symptom any PM metric in the adult subjects. These positive
      associations between various metrics of PM and respiratory symptoms in children
      suggest that children are more sensitive than adults to the effects of increased
      levels of PM air pollution or that the central site monitor was more
      representative for children who spend more time outdoors than adults. These
      findings also suggest that both larger and smaller particles can aggravate asthma
      symptoms.

PMID- 15513814
TI  - Does increased cigarette consumption nullify any reduction in lung cancer risk
      associated with low-tar filter cigarettes?
AB  - Epidemiological data suggest that smoking filter and lower tar cigarettes is
      associated with less lung cancer risk than is smoking plain and higher tar
      cigarettes. A recent National Cancer Institute monograph claimed these apparent
      benefits of lower delivery products may be illusory if relative risks are
      adjusted for daily consumption, and switching leads to "compensation" for reduced
      nicotine intake by increasing numbers of cigarettes smoked. To investigate this,
      we compared relative risks unadjusted and adjusted for daily cigarette
      consumption. Overall estimates of the filter/plain relative risk, using random
      effects meta-analysis, were 0.61 (95%confidence interval 0.54 to 0.70) for
      unadjusted data and 0.66 (0.58 to 0.76) for adjusted data. The lower tar/higher
      tar relative risk was estimated as 0.60 (0.45 to 0.81) for unadjusted data and
      0.73 (0.64 to 0.83) for adjusted data. The risk reductions were clearly seen
      regardless of gender, study location, period, or design, and when only studies
      providing both unadjusted and adjusted estimates were considered. Whether or not
      relative risk estimates are adjusted for cigarette consumption is not crucial to
      the conclusion of a clear advantage to filter cigarettes and tar reduction. Data
      on "compensation" for amount smoked were reviewed and any increase following
      switching to reduced-tar-yield cigarettes was shown to be quite small. Other
      biases in the epidemiology are also discussed, and we conclude that the apparent
      advantage to reduced-tar-delivery products is real and likely to be a marked
      underestimate of the reduction in lung cancer risk from lifetime smoking of low
      tar cigarettes.

PMID- 15513815
TI  - Adjuvant activity of ambient particulate matter in macrophage activity
      suppressed, N-acetylcysteine-treated, iNOS- and IL-4-deficient mice.
AB  - In previous studies, we have shown strong adjuvant activity for Ottawa dust (EHC
      93) after coexposure of the BALB/c mouse to EHC-93 and ovalbumin. Mice were
      intranasally sensitized at days 0 and 14 with 200 microg ovalbumin and 150 microg
      EHC-93, and challenged with ovalbumin at days 35, 38, and 41 with 200 microg
      ovalbumin. Mice were autopsied at day 42. This adjuvant activity was shown for
      the antibody response to ovalbumin (immunoglobulins E, G1, and G2a),
      histopathological lesions in the lung, cytokines, and the numbers of eosinophils
      in lung lavages. To study the mechanisms of this adjuvant activity, mice
      (BALB/cC.D2-Vil6) with natural-resistance-associated macrophage protein
      (Nramp1s), BALB/c mice pretreated with the antioxidant N-acetylcysteine (NAC),
      mice (B6.129P2-Nos2tmLau) deficient in inducible nitric oxide synthase (iNOS),
      and mice with interleukin-4 (IL-4) deficiency (BALB/cIl4< tm2Nnt) were coexposed
      to ovalbumin and EHC-93. Our studies have shown that the adjuvant activity
      induced after such coexposure does not change if the macrophage activation of the
      mice is disturbed or if the mice have been pretreated with N-acetylcysteine. In
      addition, the adjuvant activity does not develop through the pathway in which
      inducible nitric oxide synthase is involved. Because the histopathological
      lesions are statistically significant less in the IL-4 knockout strain in
      comparison with the wild type, we conclude that interleukin-4 might play an
      important role in the adjuvant activity caused by EHC-93.

PMID- 15513816
TI  - Tracheobronchial stenosis following sulfur mustard inhalation.
AB  - Sulfur mustard inhalation leads to different respiratory complications. In this
      article, we describe late stenotic effects of mustard gas inhalation on major
      airways. About 15 yr after exposure, suspect cases suffering from severe
      respiratory disorders underwent complete workup for central airway stenosis.
      Patients were evaluated with bronchoscopy and tracheal computerized tomography
      scan. The mean age of patients was 43+/-8 yr. The mean exposure time was 16+/-0.7
      yr. The mean time between injury and diagnosis of tracheobronchial stenosis was
      11.7+/-4.8 yr. Among the 33 referred cases with no other risk factor of stenosis,
      8 cases had significant stenosis in their major airways, confirmed by tracheal
      computerized tomography scan and bronchoscopy. We conclude that direct toxic
      effects of sulfur mustard can lead to tracheobronchial stenosis with different
      degrees of involvement ranging from diffuse tracheal stenosis to stenosis of the
      isolated left main bronchus or glottic and subglottic stenosis.

PMID- 15513817
TI  - Development and performance evaluation of a high-volume ultrafine particle
      concentrator for inhalation toxicological studies.
AB  - This article presents the development and performance evaluation of a high-volume
      ultrafine particle concentrator. The ultrafine particle concentrator consists of
      several units, including a size-selective inlet; a condensational growth unit; a
      series of two virtual impactors (concentrators); a thermal size restoration
      device; an air cooler; and a size-selective outlet. Ambient ultrafine particles
      are condensationally grown to supermicrometer sizes and then are concentrated by
      a factor of 40 to 50 using a two-stage virtual impactor. Subsequently, ultrafine
      particle size distribution is restored, using a thermal method. The Harvard
      ultrafine concentrated ambient particle system (HUCAPS) delivers 58 lpm of
      concentrated aerosol that can be used for in vivo or in vitro inhalation
      toxicological studies. Overall, pressure drop through the system is only 2.2 kPa,
      which is adequately low for inhalation toxicological exposure tests. The
      performance of this system was evaluated using single-component artificial
      aerosols with a variety of physicochemical properties as well as ambient air.
      These experiments showed that for an optimum supersaturation ratio of 3.0, all
      ultrafine particles grow and get concentrated by about the same enrichment
      factor, regardless of their composition and surface properties.

PMID- 15513822
TI  - Final report on the safety assessment of 6-Amino-m-Cresol, 6-Amino-o-Cresol, 4
      Amino-m-Cresol, 5-Amino-4-Chloro-o-Cresol, 5-Amino-6-Chloro-o-Cresol, and 4
      Chloro-2-Aminophenol.
AB  - Each of these ingredients function as hair colorants. 5-Amino-4-Chloro-o-Cresol
      and 5-Amino-6-Chloro-o-Cresol are identified as oxidative hair dyes, that is,
      they are combined with an oxidizing agent before being applied to the hair. 6
      Amino-m-Cresol, 6-Amino-o-Cresol, 4-Amino-m-Cresol, and 5-Amino-4-Chloro-o-Cresol
      are used in oxidative hair dyes, but it is not known if they are also used in
      nonoxidative (semipermanent) hair dyes. No toxicologically significant impurities
      are present with these two ingredients. To supplement the safety test data on
      these ingredients, available data on related ingredients (4-amino-2
      hydroxytoluene and p-,m-, and o-aminophenol) previously found safe as used by the
      Cosmetic Ingredient Review (CIR) Expert Panel were summarized. 5-Amino-4-Chloro-o
      Cresol and 5-Amino-6-Chloro-o-Cresol do not absorb significant ultraviolet
      radiation in the UVB region and none in the UVA region, although 4-Amino-m-Cresol
      had a symmetrical UV absorption peak at 300 nm. Percutaneous penetration of 5
      Amino-4-Chloro-o-Cresol and 5-Amino-6-Chloro-o-Cresol alone was significant, but
      when combined with oxidative developer, skin absorption was extremely low. Both
      of these dyes are excreted rapidly via the urine. Repeated exposure of animal
      skin to 5-Amino-4-Chloro-o-Cresol and 5-Amino-6-Chloro-o-Cresol failed to produce
      any cumulative irritation and single exposures up to 10%were not irritating to
      animal skin. 5-Amino-4-Chloro-o-Cresol and 5-Amino-6-Chloro-o-Cresol combined
      with oxidizer were not sensitizers in guinea pig maximization tests. Ocular
      irritation resulted from exposure of animals to undiluted 5-Amino-4-Chloro-o
      Cresol, but not to a 5%solution. Only minor irritation was observed with 5%5
      Amino-6-Chloro-o-Cresol. Subchronic toxicity testing in animals using 5-Amino-4
      Chloro-o-Cresol, 5-Amino-6-Chloro-o-Cresol, and 4-Amino-m-Cresol did not yield
      any adverse reactions. 6-Amino-m-Cresol and 4-Amino-m-Cresol were generally not
      mutagenic in in vitro and in vivo tests. Exposure to 5-Amino-4-Chloro-o-Cresol, 5
      Amino-6-Chloro-o-Cresol, 6-Amino-m-Cresol and 4-Amino-m-Cresol from cosmetics
      were several orders of magnitude below developmental toxicity no-observed-adverse
      effect levels (NOAELs). Although irritation data on several ingredients are
      absent, products containing these ingredients must include a caution statement
      and patch test instructions for determining whether the product causes skin
      irritation. The Expert Panel expects that following this procedure would identify
      individuals who would have an adverse reaction and allow them to avoid
      significant exposures. These compounds, when tested alone, are moderate skin
      sensitizers, but when combined with the developer, these ingredients are not
      sensitizers in animal tests. This information, coupled with the available animal
      test data, supports the safety of these ingredients in oxidative hair dyes. In
      the absence of systemic toxicity data, however, the available data are
      insufficient to support the safety of 6-Amino-o-Cresol and 4-Chloro-2-Aminophenol
      in semipermanent hair dyes. The types of data required for these two ingredients
      for this use include (1) physical and chemical properties, including the
      octanol/water partition coefficient; (2) impurities data, especially regarding
      the presence of m-cresol, other organic molecules, and heavy metals; (3) data
      demonstrating that the metabolism is similar to that of 4-amino-2-hydroxytoluene
      and/or p-,m-, and o-aminophenol, or 28-day dermal toxicity with histopathology,
      dermal reproductive toxicity data, and an in vitro genotoxicity study for 6-Amino
      o-Cresol and one genotoxicity study in a mammalian system; if positive, a 2-year
      dermal carcinogenicity study using National Toxicology Program methods may be
      needed.

PMID- 15513823
TI  - Final report of the amended safety assessment of PEG-5, -10, -16, -25, -30, and 
      40 soy sterol.
AB  - PEGs Soy Sterol are polyethylene glycol (PEG) derivatives of soybean oil sterols
      used in a variety of cosmetic formulations as surfactants and emulsifying agents,
      skin-conditioning agents, and cleansing and solubilizing agents. When the safety
      of these ingredients were first reviewed, the available data were insufficient to
      support safety. New data have since been received and the safety of these
      ingredients in cosmetics has been substantiated. Current concentration of use
      ranges from a low of 0.05% in makeup preparations to 2% in moisturizers and
      several other products. PEGs Soy Sterol are produced by the reaction of the soy
      sterol hydroxyl with ethylene oxide. In general, ethoxylated fatty acids can
      contain 1,4-dioxane as a byproduct of ethoxylation. The soy sterols include
      campesterol, stigmasterol, and beta-sitosterol. The distribution of sterols found
      in oils derived from common plants is similar, with beta-sitosterol comprising a
      major component. Impurities include sterol hydrocarbons and cholesterol (4% to
      6%) and triterpine alcohols, keto-steroids, and other steroid-like substances (4%
      to 6%). No pesticide residues were detected. PEGS: Because PEGs are an underlying
      structure in PEGs Soy Sterols, the previous assessment of PEGs was considered. It
      is generally recognized that the PEG monomer, ethylene glycol, and certain of its
      monoalkyl ethers are reproductive and developmental toxins. Given the methods of
      manufacture of PEGs Soy Sterol, there is no likelihood of ethylene glycol or its
      alkyl ethers being present. Also, the soybean oil sterol ethers in this
      ingredient are chemically different from the ethylene glycol alkyl ethers of
      concern. PEGs are not carcinogenic, although sensitization and nephrotoxicity
      were observed in burn patients treated with a PEG-based cream. No evidence of
      systemic toxicity or sensitization was found in studies with intact skin. Plant
      Phytosterols: Intestinal absorption of ingested plant phytosterols is on the
      order of 5%, with 95% of the material entering the colon. Absorbed plant
      phytosterols are transported to the blood. Although there are some data
      suggesting that sulfates of beta-sitosterol can act as abortifacients in rats and
      rabbits, other studies of well-characterized plant phytosterols and phytosterol
      esters demonstrated no effect in an estrogen-binding study, a recombinant yeast
      assay for estrogen or estrogen-like activity, or a juvenile rat uterotrophic
      assay for estrogen or estrogen-like activity. In a two-generation reproduction
      study using rats, plant phytosterol esters in the diet had no effect on any
      parameter of reproduction or fertility. Subcutaneous injections of beta
      sitosterol did reduce sperm concentrations and fertility in rats. Sitosterol
      inhibited tumor promoting activity of 12-O-tetradecanoylphorbol-13-acetate (TPA)
      in mice after initiation with 7,12-dimethylbenz[a]anthracene (DMBA), and reduced
      the tumors produced by N-methylnitrosourea in rats. Phytosterols were not
      genotoxic in several bacterial, mammalian, and in vitro assay systems.
      Phytosterols decreased epithelial cell proliferation in the colon of mice and
      rats, and were cytotoxic for human epidermoid carcinoma of the nasopharynx. PEGs
      Soy Sterols: The acute oral LD50 in rats of PEG-5-25 Soy Sterol was >10 g/kg. The
      acute dermal LD50 of a liquid eyeliner containing 2%PEG-5 Soy Sterol was >2 g/kg
      in rabbits. PEG-5-25 Soy Sterol was not a primary irritant in rabbits when
      applied undiluted. Undiluted PEG-5 Soy Sterol did not cause sensitization in
      guinea pigs. PEGs Soy Sterol did not produce ocular toxicity in rabbits. PEG-5
      Soy Sterol was negative in the Ames mutagenicity test, with or without metabolic
      activation. PEG-5 Soy Sterol, at concentrations up to 2%in formulation, did not
      cause dermal or ocular irritation, dermal sensitization, or photosensitization in
      clinical studies. Because of the possible presence of 1,4-dioxane reaction
      product and unreacted ethylene oxide residues, it was considered necessary to use
      appropriate procedures to remove these from PEGs Soy Sterol before blending them
      into cosmetic formulations. Based on the systemic toxicity and sensitization seen
      with PEGs applied to damaged skin, it was recommended that PEGs Soy Sterol should
      not be used in cosmetic products applied to damaged skin. Although no dermal
      absorption data were available, oral studies demonstrate that phytosterols and
      phytosterol esters are not significantly absorbed and do not result in
      significant systemic exposure. Some small amounts did appear in the ovaries,
      however. This raises a concern about the potential presence of free phytosterols
      and beta-Sitosterol, which could have antiestrogenic, antiprogestational,
      gonadotrophic, antigonadotrophic, and antiandrogenic effects in PEG sterols.
      These concerns are alleviated by the extensive data showing that well-defined
      phytosterols and phytosterol esters are not estrogenic and do not pose a hazard
      to reproduction. Likewise, the absence of impurities in plant phytosterols and
      phytosterol esters and extensive data demonstrating the absence of any
      genotoxicity in bacterial and mammalian systems mitigate against the possibility
      of any carcinogenic effect with those same well-characterized materials. The
      Cosmetic Ingredient Review (CIR) Expert Panel concluded that the PEGs Soy Sterol
      are safe as used in cosmetic products.

PMID- 15513824
TI  - Final report of the amended safety assessment of Dioscorea Villosa (Wild Yam)
      root extract.
AB  - Dioscorea Villosa (Wild Yam) Root Extract is an extract of the rhizomes of the
      wild yam, D. villosa. A manufacturing process was described in which cut up and
      ground rhizomes are combined with an eluant (e.g., oleyl alcohol), the plant
      material precipitated with addition of a miscible solvent, washed, and
      redissolved in the original eluant. The extract contains glycoside and steroidal
      saponins (< or =0.4%), diosgenin (< or =3.5%), alkaloids, tannins, phytosterols,
      and starch. Levels of heavy metals, 1,4-dioxane, chloroform, methylene chloride,
      trichloroethylene, and benzene are reported to be below limits of detection.
      Although only one use was reported to the U.S. Food and Drug Administration (in a
      body and hand preparation), industry reported uses in body and hand creams,
      lotions, powders, and sprays at a concentration of 0.00001% (equivalent to
      0.000002% plant solids), and in moisturizing creams, lotions, powders, and sprays
      at concentrations up to 15% (equivalent to 0.5% plant solids). Preparations
      fromD. villosaare used in herbal medicine for treatment of a variety of ailments
      and by the pharmaceutical industry in the preparation of steroids. Using
      Dioscorea Villosa (Wild Yam) Root Extract prepared via a specified process, it is
      possible to produce a stable extract with a narrow range of diosgenin content.
      The extract produced using this methodology was tested in acute and short-term
      toxicity tests, dermal irritation tests, a sensitization test, an ocular
      irritation test, a rat uterotropic assay, and genotoxicity tests. An acute oral
      toxicity test produced hypoactivity, piloerection, and dyspnea and a death in 1
      of 10 rats at 2 g/kg using the specified extract, but no toxicity in rats given
      0.5 g/kg. A dermal toxicity test using the specified extract demonstrated no
      acute toxicity in rats. Both a 7-day local tolerance test and a 28-day dermal
      toxicity test in rats produced no significant adverse effects at the maximum
      tested concentration of 10%. A single application of undiluted extract to the
      intact and abraded skin of rabbits produced sufficient irritation for the test
      material to be rated"irritant,"but a 10% dilution was not irritating. Undiluted
      extract was only mildly irritating to the conjuctiva of the rabbit eye;
      irritation in the iris and cornea was mild and transient. Undiluted extract was
      not irritating during the induction phase of a guinea pig sensitization study,
      nor did challenge with a 25% dilution elicit any sensitization. The specified
      extract at concentrations up to 500 mg/kg/day did not have any estrogenic
      activity in the juvenile rat uterotrophic assay. Genotoxicity assays in bacterial
      and mammalian systems were negative, except that Ames test strain TA 1537 was
      positive at one dose level using the plate incorporation method, but not using a
      preincubation method. Although the concentration at which the actual plant
      extract is used in cosmetic products is low, one of the primary safety concerns
      with this plant extract is the possible metabolic/endocrine activity, e.g.,
      estrogen-like or progesterone-like activity as a result of the presence of small
      amounts of plant phytosterols such as diosgenin. Extracts prepared as described
      in this safety assessment, with an upper limit of 3.5% diosgenin, did not have
      any estrogenic activity, demonstrating that it is possible to produce material
      that does not present this specific safety concern. Although extracts from
      pesticide-free plants were not considered genotoxic and it was the view of the
      Cosmetic Ingredient Review (CIR) Expert Panel that there do not appear to be any
      components that could be carcinogenic, pesticide residues could raise this issue.
      It was urged that manufacturers limit pesticide residues to the limit previously
      used for lanolin of not more than 40 ppm (with not more than 10 ppm for any one
      residue). Based on these data, it was concluded that Dioscorea Villosa (Wild Yam)
      Root Extract is safe as used in cosmetic formulations. This conclusion regarding
      safety, however, is valid only for extracts prepared in a manner that produces a
      similar chemical profile as that described in this report, particularly as
      regards diosgenin. Extracts not prepared in a manner that produces a similar
      chemical profile would be considered safe if they have a similar safety test
      profile.

PMID- 15513825
TI  - Final report of the amended safety assessment of Glyceryl Laurate, Glyceryl
      Laurate SE, Glyceryl Laurate/Oleate, Glyceryl Adipate, Glyceryl Alginate,
      Glyceryl Arachidate, Glyceryl Arachidonate, Glyceryl Behenate, Glyceryl Caprate,
      Glyceryl Caprylate, Glyceryl Caprylate/Caprate, Glyceryl
      Citrate/Lactate/Linoleate/Oleate, Glyceryl Cocoate, Glyceryl Collagenate,
      Glyceryl Erucate, Glyceryl Hydrogenated Rosinate, Glyceryl Hydrogenated Soyate,
      Glyceryl Hydroxystearate, Glyceryl Isopalmitate, Glyceryl Isostearate, Glyceryl
      Isostearate/Myristate, Glyceryl Isostearates, Glyceryl Lanolate, Glyceryl
      Linoleate, Glyceryl Linolenate, Glyceryl Montanate, Glyceryl Myristate, Glyceryl
      Isotridecanoate/Stearate/Adipate, Glyceryl Oleate SE, Glyceryl Oleate/Elaidate,
      Glyceryl Palmitate, Glyceryl Palmitate/Stearate, Glyceryl Palmitoleate, Glyceryl
      Pentadecanoate, Glyceryl Polyacrylate, Glyceryl Rosinate, Glyceryl Sesquioleate,
      Glyceryl/Sorbitol Oleate/Hydroxystearate, Glyceryl Stearate/Acetate, Glyceryl
      Stearate/Maleate, Glyceryl Tallowate, Glyceryl Thiopropionate, and Glyceryl
      Undecylenate.
AB  - The safety of 43 glyceryl monoesters listed as cosmetic ingredients was reviewed
      in a safety assessment completed in 2000. Additional safety test data pertaining
      to Glyceryl Rosinate and Glyceryl Hydrogenated Rosinate were received and served
      as the basis for this amended report. Glyceryl monoesters are used mostly as skin
      conditioning agents--emollients and/or surfactant--emulsifying agents in
      cosmetics. The following 20 glyceryl monoesters are currently reported to be used
      in cosmetics: Glyceryl Laurate, Glyceryl Alginate, Glyceryl Arachidonate,
      Glyceryl Behenate, Glyceryl Caprylate, Glyceryl Caprylate/Caprate, Glyceryl
      Cocoate, Glyceryl Erucate, Glyceryl Hydroxystearate, Glyceryl Isostearate,
      Glyceryl Lanolate, Glyceryl Linoleate, Glyceryl Linolenate, Glyceryl Myristate,
      Glyceryl Oleate/Elaidate, Glyceryl Palmitate, Glyceryl Polyacrylate, Glyceryl
      Rosinate, Glyceryl Stearate/Acetate, and Glyceryl Undecylenate. Concentration of
      use data received from the cosmetics industry in 1999 indicate that Glyceryl
      Monoesters are used at concentrations up to 12% in cosmetic products. Glyceryl
      Monoesters are not pure monoesters, but are mostly mixtures with mono-, di-, and
      tri-esters. The purity of commercial and conventional Monoglyceride (Glyceryl
      Monoester) is a minimum of 90%. Glyceryl Monoesters (monoglycerides) are
      metabolized to free fatty acids and glycerol, both of which are available for the
      resynthesis of triglycerides. Glyceryl Laurate enhanced the penetration of drugs
      through cadaverous skin and hairless rat skin in vitro and has been described as
      having a wide spectrum of antimicrobial activity. A low-grade irritant response
      was observed following inhalation of an aerosol containing 10% Glyceryl Laurate
      by test animals. Glyceryl monoesters have little acute or short-term toxicity in
      animals, and no toxicity was noted following chronic administration of a mixture
      consisting mostly of glyceryl di- and mono- esters. Glyceryl Laurate did have
      strong hemolytic activity in an in vitro assay using sheep erythrocytes. Glyceryl
      Laurate, Glyceryl Isostearate, or Glyceryl Citrate/Lactate/Linoleate/Oleate were
      not classified as ocular irritants in rabbits. Undiluted glyceryl monoesters may
      produce minor skin irritation, especially in abraded skin, but in general these
      ingredients are not irritating at concentrations used in cosmetics. Glyceryl
      monoesters are not sensitizers, except that Glyceryl Rosinate and Hydrogenated
      Glyceryl Rosinate may contain residual rosin, which can cause allergic reactions.
      These ingredients are not photosensitizers. Glyceryl
      Citrate/Lactate/Linoleate/Oleate was not mutagenic in the Ames test system.
      Glyceryl Laurate exhibited antitumor activity and Glyceryl Stearate was negative
      in a tumor promotion assay. At concentrations higher than used in cosmetics,
      Glyceryl Laurate did cause moderate erythema in human repeat-insult patch test
      (RIPT) studies, but the other glyceryl monoesters tested failed to produce any
      significant positive reactions. Glyceryl Rosinate was irritating to animal skin
      at 50%, but did not produce sensitization in clinical tests at concentrations up
      to 10% and covered with semioccluded patches. There is reported use of Glyceryl
      Rosinate at 12%in mascara, which is somewhat higher than the concentration in the
      clinical testing. It was reasoned that the available data do support the safety
      of this use because there would be minimal contact with the skin and no
      occlusion. The safety of Arachidonic Acid was not documented and substantiated
      for cosmetic product use in an earlier safety assessment and those same safety
      questions apply to Glyceryl Arachidonate. Based on these data, the Cosmetic
      Ingredient Review (CIR) Expert Panel found that these glyceryl monoesters are
      safe as cosmetic ingredients in the present practices of use and concentration:
      except that the available data are insufficient to support the safety of Glyceryl
      Arachidonate. Additional data needed to support the safety of Glyceryl
      Arachidonate include (1) dermal absorption data; and, based on the results of the
      absorption studies, there may be a need for (2) immunomodulatory data; (3)
      carcinogenicity and photocarcinogenicity data; and (4) human irritation,
      sensitization, and photosensitization data.

PMID- 15513828
TI  - Genetically modified foods: why the public frenzy? Role of mainstream news media.

PMID- 15513829
TI  - History of the Journal of the American College of Toxicology.
AB  - This companion article to the History of the American College of Toxicology also
      is written in celebration of the 25th Anniversary of the American College of
      Toxicology (ACT). It relates how the official journal of the College evolved from
      a privately owned publication, the Journal of Environmental Pathology and
      Toxicology (JEPT), into publications owned and managed by the College and its
      Board, for the first 17 years as the Journal of the American College of
      Toxicology (JACT) and currently as The International Journal of Toxicology (IJT).
      It relates how the first journal focused on toxicological studies, potential
      cancer causes and concerns associated with environmental contamination and
      chemical exposure safety issues. It tells how this journal was replaced by one
      more broadly based that addressed multiple industries and regulatory approaches,
      accepted previously unpublishable "no-effect" studies, so important in
      eliminating unwarranted animal use, and provided review articles, rather than
      only original research. It also described how the JACT evolved into an
      international journal finally recognized for its quality reviews and peer
      reviewed research. Each of the three journals that represented the College is
      described, as well as interesting events associated with their development and
      publication, including the activities and contributions of the first four editors
      in chief, Drs. Myron A. Mehlman, Mildred S. Christian, Robert M. Diener and
      Harihara Mehendale.

PMID- 15513830
TI  - History of the American College of Toxicology (ACT).
AB  - This manuscript is one of two written to celebrate the 25th Anniversary of the
      American College of Toxicology (ACT). This history of ACT describes its evolution
      from an entrepreneurial, risk taking model to a conservative business model,
      fully accepted in the scientific community. ACT started with a small group of
      scientists who were dissatisfied with the relatively narrow approach to full
      membership then taken by the Society of Toxicology (SOT). They were excited by
      new research and collaborative opportunities resulting from an enhanced public
      awareness of the impact of chemicals on the environment and emerging new
      methodologies to evaluate human risks of exposure to be chemicals and
      pharmaceuticals. These toxicologists, many of whom were from industry and
      government, rather than academia, were tired of being considered socond class
      citizens and envisioned more open and cross-disciplined approaches. They favored
      balanced input by academia, industry and government in the overall toxicologic
      evaluation and risk assessment process. The history of the founding and early
      development of ACT, as well as the College's growth and eventual acceptance into
      the scientific community, including its impact on the status quo during the
      Society's first 25 years, are told by its successive presidents.

PMID- 15513831
TI  - Bioavailability and risk assessment of orally ingested polycyclic aromatic
      hydrocarbons.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are a family of toxicants that are
      ubiquitous in the environment. These contaminants generate considerable interest,
      because some of them are highly carcinogenic in laboratory animals and have been
      implicated in breast, lung, and colon cancers in humans. These chemicals commonly
      enter the human body through inhalation of cigarette smoke or consumption of
      contaminated food. Of these two pathways, dietary intake of PAHs constitutes a
      major source of exposure in humans. Although many reviews and books on PAHs have
      been published, factors affecting the accumulation of PAHs in the diet, their
      absorption following ingestion, and strategies to assess risk from exposure to
      these hydrocarbons following ingestion have received much less attention. This
      review, therefore, focuses on concentrations of PAHs in widely consumed dietary
      ingredients along with gastrointestinal absorption rates in humans. Metabolism
      and bioavailability of PAHs in animal models and the processes, which influence
      the disposition of these chemicals, are discussed. The utilitarian value of
      structure and metabolism in predicting PAH toxicity and carcinogenesis is also
      emphasized. Finally, based on intake, disposition, and tumorigenesis data, the
      exposure risk to PAHs from diet, and contaminated soil is presented. This
      information is expected to provide a framework for refinements in risk assessment
      of PAHs from a multimedia exposure perspective.

PMID- 15513832
TI  - Contamination is a frequent confounding factor in toxicology studies with
      anthraquinone and related compounds.
AB  - Anthraquinone (AQ) (9,10-anthracenedione) is an important compound in commerce.
      Many structurally related AQ derivatives are medicinal natural plant products.
      Examples include 1-hydroxyanthraquinone (1-OH-AQ) and 2-hydroxyanthraquinone (2
      OH-AQ), which are also metabolites of AQ. Some commercial AQ is produced by the
      oxidation of anthracene (AQ-OX). In the recent past, the anthracene used was
      distilled from coal tar and different lots of derived AQ often contained
      polycyclic aromatic hydrocarbon contaminants, particularly 9-nitroanthracene (9
      NA). Many toxicology studies on AQ used contaminated anthracene-derived AQ-OX,
      including a National Toxicology Program (NTP) 2-year cancer bioassay that
      reported a weak to modest increase in tumors in the kidney and bladder of male
      and female F344/N rats and in the livers of male and female B6C3F1 mice. The AQ
      OX used in that bioassay was mutagenic and contained 9-NA and other contaminants.
      In contrast, purified AQ is not genotoxic. The purpose of this paper is to
      provide additional information to help iterpret the NTP cancer bioassay. This
      paper describes a quantitative analytical study of the NTP anthracene-derived AQ
      OX test material, and presents the results of mutagenicity studies with the 1-OH
      AQ and 2-OH-AQ metabolites and the primary contaminant 9-NA. Purified 1-OH-AQ and
      2-OH-AQ exhibited only weak mutagenic activity in selected strains of tester
      bacteria and required S9. Literature reports of potent mutagenic activity for 1
      OH-AQ and 2-OH-AQ in bacteria minus S9 are, once again, very likely the result of
      the presence of contaminants in the test samples. Weak activity and limited
      production of the 1-OH-AQ and 2-OH-AQ metabolites are possible reasons that AQ
      fails to exhibit activity in numerous genotoxicity assays. 9-NA was mutagenic in
      tester strains TA98 and TA100 minus S9. This pattern of activity is consistent
      with that seen with the contaminated AQ-OX used in the NTP bioassay. Analysis of
      all the mutagenicity and analytical data, however, indicates that the mutagenic
      contamination in the NTP bioassay probably resides with compounds in addition to
      9-NA. 9-NA exhibited potent mutagenic activity in the L5178Y mammalian cell
      mutagenicity assay in the presence of S9. The positive response was primarily
      associated with an increase in small colony mutants suggesting a predominance of
      a clastogenic mechanism. Quantitative mutagenicity and carcinogenicity potency
      estimates indicate that it is plausible that the contaminants alone in the NTP AQ
      OX bioassay could have been responsible for all of the observed carcinogenic
      activity. Although AQ-OX is no longer commercially used in the United States,
      many of the reported genotoxicity and carcinogenicity results in the literature
      for AQ and AQ derivative compounds must be viewed with caution.

PMID- 15513866
TI  - The microcirculation in severe malaria.
AB  - Severe malaria in humans and animals is initiated by interactions between malaria
      infected cells, host blood cells (including monocytes, T cells and platelets) and
      endothelial cells of the microcirculation. Adhesion to vascular cells, and
      possible vascular obstruction in severe human disease, involves interaction
      between host receptors and parasite-derived proteins, such as the variant antigen
      Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1). Our understanding
      of how different PfEMP1 variants may target infected erythrocytes to specific
      sites, such as the placenta, is rapidly increasing. However, in most instances
      downstream immune-mediated inflammatory processes appear more central than
      parasite accumulation to development of severe malaria. Using genetically
      manipulated animal models of severe malaria, key roles for CD8 T cells and
      mediators such as lymphotoxin in the pathogenesis of murine disease have been
      established. Experimental and human studies suggest vascular deposition of
      activated platelets may have a central role. Here, we review some recent advances
      in the understanding of severe malaria pathogenesis from human and animal
      studies, focusing on events at the level of the microcirculation, and highlight
      the role for activated host cells in initiating the pathology of the disease.

PMID- 15513867
TI  - Retinal endothelial angiogenic activity: effects of hypoxia and glial (Muller)
      cells.
AB  - OBJECTIVE: To explore the impact of retinal glial (Muller) cells on survival and
      neovascularization-related activities of cultured retinal endothelial cells under
      normoxic and hypoxic conditions. METHODS: Bovine retinal endothelial cells
      (BRECs) were cultured under normoxia or hypoxia (0.5% O2) either alone, together
      with the human Muller cell line MIO-M1, or in normoxia- or hypoxia-conditioned
      media of MIO-M1 cells. Cell number, proliferation, apoptotic cell death, and
      migration of BRECs were determined. RESULTS: Exposure of BRECs to hypoxia for 24
      h decreased the number of adherent cells and the proliferation rate, but
      increased apoptosis and cell migration. Increased apoptosis and decreased
      proliferation of the BRECs occurred also in the presence of conditioned media of
      MIO-M1 cells. Under normoxic conditions, co-culture with MIO-M1 cells resulted in
      increased proliferation, but decreased apoptosis and migration rates of BRECs.
      Under hypoxic conditions, the Muller cells released elevated amounts of VEGF but
      their presence decreased proliferation, apoptosis and the migration rates of
      BRECs. CONCLUSIONS: Hypoxia inhibits the proliferation of retinal endothelial
      cells. Muller cells release soluble mediators that enhance this hypoxia-mediated
      effect but, under certain conditions (i.e., in co-culture), may protect retinal
      endothelial cells from apoptosis, thus supporting their survival. Altogether the
      findings indicate that the key signal necessary to trigger retinal endothelial
      proliferation under hypoxia remains to be determined.

PMID- 15513868
TI  - Remote liver injury is attenuated by adenovirus-mediated gene transfer of heme
      oxygenase-1 during the systemic inflammatory response syndrome.
AB  - OBJECTIVES: Adenovirus-mediated gene therapy is being investigated with
      increasing success for future treatment of autoimmune diseases. However, the use
      of adenoviruses is still limited by inflammatory and immune responses in the
      target organ. Previous work by the authors' laboratory established that the
      adenovirus encoding inducible heme oxygenase (Ad-HO-1) does not elicit the acute
      hepatic inflammation normally caused by adenoviruses, inviting further
      investigation in models of severe inflammation. Concurrently, there is increasing
      evidence for an endogenous protective role for heme oxygenase (HO) in the liver
      during the systemic inflammatory response syndrome (SIRS). Building on our
      previous results, this study investigated the effect of Ad-HO-1 pretreatment on
      remote liver injury during normotensive SIRS, induced by bilateral hind limb
      ischemia and reperfusion. METHODS: Microvascular perfusion and hepatocyte death
      were quantified using established intravital videomicroscopy techniques.
      Hepatocellular injury and liver function were assessed using blood-borne
      indicators. RESULTS: Microvascular perfusion deficits and increased hepatocyte
      death occurred following limb ischemia and 3 h of reperfusion in vehicle
      pretreated animals; however, Ad-HO-1 pretreatment prevented these deficits. In
      contrast, the increase in serum alanine transaminase levels was unaffected by Ad
      HO-1 pretreatment. Serum bilirubin levels were increased during systemic
      inflammation, predominantly in the conjugated form; and, this increase was
      prevented by administration of Ad-HO-1. CONCLUSIONS: These data indicate that
      gene transfer of inducible HO is an effective method to protect the liver during
      SIRS, providing incentive for further investigation into gene therapy strategies
      exploiting this anti-inflammatory enzyme.

PMID- 15513869
TI  - Hypercholesterolemia promotes leukocyte-dependent platelet adhesion in murine
      postcapillary venules.
AB  - OBJECTIVE: Leukocyte-platelet aggregates form in blood during the development of
      cardiovascular diseases, including atherosclerosis. The study determined whether
      leukocytes contribute to the platelet adhesion induced by hypercholesterolemia in
      postcapillary venules. METHODS: Wild-type (WT) C57Bl/6 or CD18-deficient (CD18-/
      ) mice were placed on a normal (ND) or high-cholesterol (HC) diet for 2 weeks.
      Platelets isolated from ND, HC, or CD18-/- mice were fluorescently labeled with
      CFSE, and administered to either ND, HC, HC-CD18-/- or anti-neutrophil serum (HC
      ANS)-treated mice. Rhodamine 6G was administered to label and visualize
      leukocytes. Intravital fluorescence microscopy was used to quantify leukocyte and
      platelet adhesion in intestinal postcapillary venules. RESULTS: HC increased both
      leukocyte and platelet adhesion (relative to ND). Greater than 50% of adherent
      platelets in HC mice were bound to adherent leukocytes. When HC platelets were
      examined in HC-ANS-treated or HC-CD18-/- mice, leukocyte-dependent platelet
      adhesion was significantly attenuated. Conversely, when HC-CD18-/- platelets were
      observed in HC recipients both leukocyte-dependent and endothelium-dependent
      platelet adhesion was comparable to HC mice receiving WT platelets. CONCLUSIONS:
      The findings demonstrate that the pro-thrombogenic phenotype assumed in the
      microvasculature during hypercholesterolemia is largely attributed to leukocyte
      dependent platelet adhesion.

PMID- 15513870
TI  - In vivo properties of potassium channels in cerebral blood vessels during
      diabetes mellitus.
AB  - OBJECTIVE: While potassium (K+) channels are important in basal tone and
      dilatation of large and small cerebral vessels, the effect of diabetes mellitus
      on K+ channels remains unclear. The goal of this study was to identify the
      influence of diabetes on responses of cerebral vessels to inhibition/activation
      of K+ channels. METHODS: The authors measured in vivo responses of pial
      arterioles and the basilar artery to inhibition/activation of K+ channels in
      nondiabetic and diabetic rats using intravital microscopy. RESULTS: Pial
      arterioles from nondiabetic and diabetic rats constricted to barium chloride
      (BaCl2) and 4-aminopyridine (4-AP). However, the magnitude of vasoconstriction to
      BaCl2 was greater in nondiabetic than in diabetic rats. Tetraethylammonium (TEA)
      did not alter diameter of pial arterioles in nondiabetic or diabetic rats. In
      addition, dilatation of pial arterioles to KCl and NS-1619 was less in diabetic
      compared to nondiabetic rats. The basilar artery from nondiabetic and diabetic
      rats constricted in a similar manner to BaCl2 and 4-AP. In contrast,
      vasoconstriction to TEA was greater in diabetic than nondiabetic rats. Similar to
      that reported for pial arterioles, dilatation of the basilar artery to KCl and NS
      1619 was less in diabetic than nondiabetic rats. CONCLUSIONS: Inward-rectifier
      (Kir) and voltage-dependent (Kv), but not calcium-activated (Kca), K+ channels
      are active under basal conditions in pial arterioles, while Kir, Kv, and Kca are
      active under basal conditions in the basilar artery of nondiabetic and diabetic
      rats. In addition, activation of Kir and Kca channels produces less cerebral
      vasodilatation in diabetic compared to nondiabetic rats. These findings provide
      new and important information regarding the influence of diabetes on the role of
      K+ channels in the regulation of cerebral vascular diameter.

PMID- 15513871
TI  - Inhibitory effects of TSG-6 Link module on leukocyte-endothelial cell
      interactions in vitro and in vivo.
AB  - OBJECTIVE: The authors investigated whether the anti-inflammatory protein tumor
      necrosis factor (TNF)-stimulated gene-6 (TSG-6) and its Link module (Link_TSG6)
      could affect the complex multistep process of leukocyte/endothelial cell (EC)
      interaction. METHODS: Mouse mesenteries were inflamed with interleukin (IL)-1beta
      and the extent of leukocyte rolling, adhesion, and emigration was determined
      after 2 h. Link_TSG6 and a single-point mutant (termed K13E) were given
      intraperitoneally together with the cytokine. Human neutrophil chemotaxis and
      transmigration were determined in vitro in response to IL-8 and/or TNF-alpha. TSG
      6, Link_TSG6, and K13E were added to the leukocytes or the EC monolayers.
      RESULTS: Co-injection of Link_TSG6 with IL-1beta selectively inhibited cell flux,
      adhesion, and emigration as analyzed in mesenteric postcapillary venules. The
      fewer cells that rolled in the animals treated with Link_TSG6 displayed a
      velocity similar to that measured in vehicle-treated mice. In vitro, Link_TSG6
      did not affect neutrophil chemotaxis or EC activation but did inhibit neutrophil
      transmigration across EC monolayers. The latter effect was shared by full-length
      TSG-6 and observed equally in response to IL-8 or TNF-alpha. CONCLUSIONS: These
      data restrict the site of action for at least some of the anti-inflammatory
      effects ascribed to TSG-6/Link_TSG6 to the microenvironment of the extravasating
      leukocyte.

PMID- 15513872
TI  - Ethanol binging enhances hepatic microvascular responses to acetaminophen in
      mice.
AB  - OBJECTIVE: Chronic alcoholism has been considered to be a risk for acetaminophen
      (APAP) hepatotoxicity, but little is known about the effect of binge alcohol
      drinking on APAP-induced liver injury. The present study was conducted to examine
      the effect of ethanol binging on APAP-induced hepatic microcirculatory
      dysfunction. METHODS: Male C57Bl/6 mice received 3 weekly ethanol binges (4 g/kg
      every 12 h x 5 doses/ week) or water binges. At 12 h after the last gavage, APAP
      (300 mg/kg) was given by oral gavage. In one group of mice, gadolinium chloride
      (GdCl3, 10 mg/kg) was intraperitoneally administered 2 and 1 days before the
      start of each weekly ethanol binge. RESULTS: Ethanol binging enhanced APAP
      induced liver injury as indicated by ALT levels. Intravital microscopic study
      showed that APAP further increased the area occupied by infiltrated erythrocytes
      into the extrasinusoidal space as well as Kupffer cell phagocytic activity in
      ethanol-binged mice when compared with water-binged mice, while no significant
      differences in sinusoidal perfusion and leukocyte adhesion were observed. ALT
      levels after APAP were exacerbated in ethanol-binged mice treated with GdCl3, but
      APAP-induced hepatic microcirculatory dysfunction was not changed significantly.
      CONCLUSIONS: These results suggest that ethanol binging increases APAP-induced
      liver injury by exacerbating infiltration of the Disse space with blood cells.
      Kupffer cells exert a protective role in the liver against APAP intoxication
      following ethanol binging.

PMID- 15513891
TI  - Estimated exposure to phthalates in cosmetics and risk assessment.
AB  - Some phthalates such as di(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate
      (DBP) and their metabolites are suspected of producing teratogenic or endocrine
      disrupting effects. To predict possible human exposure to phthalates in
      cosmetics, the levels of DEHP, diethyl phthalate (DEP), DBP, and butylbenzyl
      phthalate (BBP) were determined by high-performance liquid chromatography (HPLC)
      in 102 branded hair sprays, perfumes, deodorants, and nail polishes. DBP was
      detected in 19 of the 21 nail polishes and in 11 of the 42 perfumes, and DEP was
      detected in 24 of the 42 perfumes and 2 of the 8 deodorants. Median exposure
      levels to phthalates in cosmetics by dermal absorption were estimated to be
      0.0006 g/kg body weight (bw)/d for DEHP, 0.6 g/kg bw/d for DEP, and 0.103 g/kg
      bw/d for DBP. Furthermore, if phthalates in cosmetics were assumed to be absorbed
      exclusively via 100% inhalation, the median daily exposure levels to phthalates
      in cosmetics were estimated to be 0.026 g/kg bw/d for DEHP, 81.471 g/kg bw/d for
      DEP, and 22.917 g/kg bw/d for DBP, which are far lower than the regulation levels
      set buy the Scientific Committee on Toxicity, Ecotoxicity, and the Environment
      (CSTEE) (37 g/kg bw/d, DEHP), Agency for Toxic Substances and Disease Registry
      (ATSDR) (7000 g/kg bw/d, DEP), and International Programme on Chemical Safety
      (IPCS) (66 g/kg bw/d, DBP), respectively. Based on these data, hazard indices
      (HI, daily exposure level/regulation level) were calculated to be 0.0007 for
      DEHP, 0.012 for DEP, and 0.347 for DBP. These data suggest that estimated
      exposure to-phthalates in the cosmetics mentioned are relatively small. However,
      total exposure levels from several sources may be greater and require further
      investigation.

PMID- 15513892
TI  - Determination of chromosome aberrations in workers in a petroleum refining
      factory.
AB  - Human exposure to benzene is derived occupationally from the petrochemical and
      petroleum refining industries. This study was performed to determine whether the
      frequencies of chromosome aberrations in workers exposed to low levels of benzene
      in a petroleum refining factory were elevated compared to an unexposed control
      group. The study population was comprised of 178 exposed workers and 36 unexposed
      workers. The frequencies of chromatid deletions and total chromosome aberrations
      in workers exposed to benzene were significantly higher compared to the unexposed
      control group. The frequency of total chromosome aberration was 4.20 per 500
      metaphase cells in the exposed workers, whereas the frequency was 2.24 per 500
      metaphase cells in the unexposed control group. The frequencies of total
      chromosome aberrations were significantly associated with benzene concentration
      after adjusting for confounding variables such as age, smoking status, and
      alcohol intake. The frequencies of chromosome aberrations were significantly
      increased in workers with low white blood cell counts (below 4000 cells/mm3)
      compared to those with high white blood cell counts (above 4000 cells/mm3). A
      reduced white blood cell count (below 4000/mm3) is suggestive of chronic exposure
      to benzene. In conclusion chronic benzene exposure and preclinical signs, such as
      reduced white blood cell counts, may be monitored by chromosome aberrations
      analysis.

PMID- 15513893
TI  - Modulation of murine macrophage function by methamphetamine.
AB  - The abuse of methamphetamine (MA) is an increasingly growing problem globally and
      produces serious side effects. In the present study, the immunomodulating effects
      of MA were examined on murine peritoneal macrophages after MA (5 mg/kg body
      weight) was administered daily orally for 2 wk. When purified macrophages were
      stimulated with lipopolysaccharide (LPS), the tumoricidal activity induced by LPS
      was significantly suppressed by MA. MA also inhibited poly I:C-induced antiviral
      activity in macrophages and decreased the number of peritoneal macrophages. FACS
      analysis showed that the expression of CD14 was markedly decreased by MA in LPS
      stimulated macrophages. The production of nitric oxide (NO) and tumor necrosis
      factor (TNF)-alpha: which are known to be major effector molecules in macrophage
      mediated cytotoxicity, was decreased by MA. MA produced a significant effect on
      phagocytosis and interleukin-1 (IL-1) and IL-6 at 14 d. In addition, the level of
      hydrogen peroxide (H2O2) was not altered by MA. Taken together, these data
      indicate that MA has a differential immunomodulating effect on macrophage
      secretory and cellular activities.

PMID- 15513894
TI  - 2-Hydroxyestradiol induces oxidative DNA damage and apoptosis in human mammary
      epithelial cells.
AB  - Catechol estrogens, the hydroxylated metabolites of 17beta-estradiol (E2), have
      been considered to be implicated in estrogen-induced carcinogenesis. 2
      Hydroxyestradiol (2-OHE2), a major oxidized metabolite of E2 formed
      preferentially by cytochrome P-450 1A1, reacts with DNA to form stable adducts
      and exerts genotoxicity. 2-OHE2 can be oxidized to quinone, which is accompanied
      by generation of reactive oxygen species (ROS). In the present study, 2-OHE2
      induced strand scission in phiX174 phage DNA and oxidative base modifications in
      calf thymus DNA in the presence of cupric ion. In cultured human mammary
      epithelial (MCF-10A) cells, 2-OHE2 treatment produced ROS accumulation, 8-oxo-7,8
      dihydroxy-2'-deoxyguanosine formation, cytotoxicity, and disruption of
      mitochondrial transmembrane potential, all of which were prevented by N
      acetylcysteine. These findings, taken together, suggest that 2-OHE2-induced
      oxidative DNA damage and apoptosis in MCF-10A cells might be mediated by ROS
      generated via the redox cycling of this catechol estrogen.

PMID- 15513895
TI  - Skf 525-A induces cocaine N-demethylase, ethoxyresorufin O-deethylase, and
      pentoxyresorufin O-dealkylase activities by induction of cytochrome p-450 2B in
      female B6C3F1 mice.
AB  - Studies demonstrated that cocaine-induced immunosuppression is mediated by
      metabolites of cocaine. Although SKF 525-A inhibited cocaine N-demethylation in
      liver S9 fractions isolated from female B6C3F1 mice, our study showed that
      pretreatment of mice with SKF 525-A potentiated cocaine-induced suppression of
      the antibody response to sheep red blood cells. An increase in formaldehyde
      generation was subsequently shown following incubation of cocaine with the S9
      fractions prepared from SKF 525-A-treated mice, indicating the possibility of
      cytochrome P-450 (CYP) induction. Therefore, the inductive effects of SKF 525-A
      on CYP enzyme activities and proteins were investigated in female B6C3F1 mice to
      elucidate the potentiation of cocaine-induced immunosuppression by SKF 525-A.
      When SKF 525-A was administered at 10, 20, or 40 mg/kg/d intraperitoneally for 7
      consecutive days, both ethoxyresorufin O-deethylase and pentoxyresorufin O
      dealkylase activities were induced dose-dependently. Furthermore, the induction
      of enzymatic activity was time dependent. Meanwhile, when the type of isozyme
      induced by SKF 525-A was analyzed by Western immunoblotting with monospecific
      anti-CYP 1A and anti-CYP 2B antibodies, only the CYP 2B appeared to be induced.
      From in vitro inhibition studies with monoclonal antibodies, it was confirmed
      that the induced activity of ethoxyresorufin O-deethylase by SKF 525-A was due to
      increased levels of CYP 2B proteins. Our present results provide an explanation
      for the potentiation of cocaine-induced immunosuppression by repeated exposure to
      SKF 525-A. Our results also indicate that ethoxyresorufin O-deethylase, a
      selective substrate for CYP 1A, may also be catalyzed by CYP 2B.

PMID- 15513896
TI  - Physiologically based pharmacokinetics of bisphenol A.
AB  - A physiologically based pharmacokinetic (PBPK) model consisting of vein, artery,
      lung, liver, spleen, kidneys, heart, testes, muscle, brain, adipose tissue,
      stomach, and small intestine was developed to predict the tissue distribution and
      blood pharmacokinetics of bisphenol A in rats and humans. To demonstrate the
      validity of the developed PBPK model, bisphenol A was administered to rats by
      multiple iv injections to steady state. The PBPK model predicted the steady-state
      levels of bisphenol A in blood and various tissues observed in rats after
      multiple iv injections. The PBPK model was further applied to predict blood and
      various tissue levels of bisphenol A in a 70 kg-human after single iv injection
      (5-mg dose) and multiple oral administrations to steady state (100-mg doses every
      24 h). The simulated steady-state human blood levels (0.9-1.6 ng/ml) were
      comparable to basal blood levels of bisphenol A reported in literature (1.49
      ng/ml). Furthermore, pharmacokinectic parameters of CL (116.6 L/h), Vss (141.8
      L), and t1/2 (76.8 min) predicted for humans were comparable to those previously
      predicted by simple allometric scaling. This PBPK model may provide insights into
      the tissue distribution characteristics as a result of human exposure to
      bisphenol A.

PMID- 15513897
TI  - Potent inhibition of recombinant human cytochrome p-450 1A1 by
      pentamethoxystilbene.
AB  - Previously it was reported that various hydroxystilbene compounds strongly
      inhibit human cytochrome P-450 1 enzymes and were postulated as candidate
      chemopreventive agents. In this study, the inhibitory potential of P-450 1 enzyme
      activities by 3,5,3,4,5-pentamethoxystilbene (PMS), a synthetic stilbene
      compound, was evaluated with the Escherichia coli (E. coil) membranes of
      recombinant human cytochrome P-450 1A1, 1A2, or 1B1 coexpressed with human NADPH
      P-450 reductase. PMS produced a significant inhibition of ethoxyresorufin O
      deethylation (EROD) activities with IC50 values of 0.14, 934, and 3.2 M for 1A1,
      1A2, and 1B1, respectively. PMS did not significantly inhibit EROD activities in
      human liver microsomes. To elucidate the mechanism of inhibition by PMS, kinetic
      studies were performed. Analysis of the mode of inhibition indicated a mixed-type
      inhibition of P-450 1A1. The inhibition of P-450 1A1-mediated EROD activity by
      PMS was not irreversible-mechanism based. The loss of EROD activity of P-450 1A1
      with PMS was blocked by trapping agents such as glutathione, N-acetylcysteine, or
      dithiothreitol. Moreover, PMS significantly suppressed P-450 1A1-mediated EROD
      activity and P-450 1A1 gene expression in HepG2 cells induced by 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD). Taken together, the results suggested that
      PMS is a potent and selective inhibitor of human P-450 1A1 and may be considered
      for use as a cancer chemopreventive agent in humans.

PMID- 15513898
TI  - Mechanism of antifertility in male rats treated with 3-monochloro-1,2-propanediol
      (3-MCPD).
AB  - 3-Monochloro-1,2-propanediol (3-MCPD) is a food contaminant that is often found
      in foods containing acid-hydrolyzed (AH) protein, like seasonings and savory food
      products. The purpose of the present study was to investigate the effects of 3
      MCPD on male fertility, sperm, and hormonal levels and its antifertility
      mechanism. In vivo male fertility testing was performed to observe the adverse
      effects of 3-MCPD on the functioning of the male reproductive system and
      pregnancy outcome. 3-MCPD (0.01-5 mg/kg) was administered daily by gavage to
      Sprague-Dawley (SD) male rats for 4 wk. At the end of the pretreatment period,
      male rats were mated overnight with untreated females. Males successfully
      inducing pregnancy were sacrificed to assess sperm parameters, reproductive organ
      histopathology, and spermatogenesis. The resulting pregnant females were
      sacrificed on 20 of gestation to evaluate pregnancy outcome. The paternal
      administration of 3-MCPD (5 mg/kg) was found to result in adverse effects on male
      fertility and pregnancy outcome without inducing remarkable histopathological
      changes in testes and epididymides. Additionally, 3-MCPD (5 mg/kg) significantly
      reduced sperm motility, copulation, fertility indices, and the number of live
      fetuses showed steep dose-response curves. 3-MCPD did not affect spermatogenesis
      or induce hormonal changes in the blood and testes of male rats. An in vitro
      hormone assay using primary isolated Leydig cells showed no significant changes
      in related hormone levels after 3-MCPD treatment. To evaluate the effects of 3
      MCPD on apoptotic induction and H+-ATPase levels in the testis and epididymis, 10
      or 100 mg/kg of 3-MCPD was administered by gavage to male rats and testes and
      epididymides were examined at 3, 6, 12, and 24 h later. Apoptosis was not
      detected in the testes of animals treated with 100 mg/kg 3-MCPD. However, the
      level of H+-ATPase in the cauda epididymis was reduced by 3-MCPD treatment. These
      results indicate that 3-MCPD induced a spermatotoxic effect, which was mediated
      by reduced H+-ATPase expression in the cauda epididymis, and suggest that an
      altered pH level in the cauda epididymis might lead to a disruption of sperm
      maturation and the acquisition of motility.

PMID- 15513899
TI  - Deprenyl, a therapeutic agent for Parkinson's disease, inhibits arsenic toxicity
      potentiated by GSH depletion via inhibition of JNK activation.
AB  - Previously, studies reported that depletion of cellular GSH by sulfur amino acid
      deprivation (SAAD) potentiated arsenic (As)-induced cytotoxicity through
      activation of mitogen-activated protein (MAP) kinases. Deprenyl (selegiline), a
      selective inhibitor of monoamine oxidase B that is responsible for oxidative
      metabolism of dopamine, has been used as a therapeutic agent for the treatment of
      Parkinson's disease. This study investigated (1) whether deprenyl inhibited As
      induced toxicity or As toxicity that was potentiated by glutathione (GSH)
      depletion and (2) whether deprenyl affected MAP kinase activation. Deprenyl
      protected H4IIE cells against the toxicity induced by As + SAAD in a
      concentration-dependent manner, but not by As alone. Activation of JNK by SAAD or
      As, but not that of p38 kinase or ERK1/2, was inhibited by treatment of cells
      with deprenyl. The cells that had been exposed to As or SAAD exhibited decreases
      in mitochondrial permeability to rhodamine 123, which was restored by deprenyl
      treatment or transfection with the plasmid encoding a dominant negative mutant of
      JNK [JNK1( )]. Transfection of H4IIE cells with the JNK1( ) plasmid, however,
      failed to protect cells against As toxicity. These results showed that deprenyl
      inhibits As toxicity potentiated by cellular GSH depletion, but not the toxicity
      induced by As alone. The cytoprotective effect of deprenyl may be mediated with
      restoration of mitochondrial function via its inhibition of JNK1.

PMID- 15513900
TI  - Phthalates inhibit tamoxifen-induced apoptosis in MCF-7 human breast cancer
      cells.
AB  - Environmental estrogens represent a class of compounds that can mimic the
      function or activity of the endogenous estrogen 17 -estradiol (E2). Phthalates
      including butyl benzyl phthalate (BBP), di(n-butyl) phthalate (DBP), and di(2
      ethylhexyl) phthalate (DEHP) are used as plasticizers, and also widely used in
      food wraps and cosmetic formulations. Phthalates have been shown to mimic
      estrogen and are capable of binding to the estrogen receptor (ER). It has been
      demonstrated that estrogen promotes drug resistance to tamoxifen (TAM) in breast
      cancer. In order to further evaluate the potential role of the phthalates as
      environmental estrogens, the effect of phthalates was investigated on TAM-induced
      apoptosis in MCF-7 human breast cancer cells. Our results show that phthalates,
      BBP (100 M), DBP (10 M), and DEHP (10 M), significantly increased cell
      proliferation in MCF-7, but not in MDA-MB-231 cells. In addition, BBP, DBP, and
      DEHP mimicked estrogen in the inhibition of TAM-induced apoptosis in MCF-7 cells.
      Our data suggest that the inhibitory effect of phthalates on TAM-induced
      apoptosis involves an increase in intracellular Bcl-2 to Bax ratio. Given that
      the phthalates are widely used in cosmetics mainly for women, our findings that
      revealed the promoting effect of BBP, DBP, and DEHP on chemotherapeutic drug
      resistance to TAM in breast cancer may be of biological relevance.

PMID- 15513901
TI  - Genotoxicity evaluation of Isaria sinclairii (ISE) extract.
AB  - The mutagenic potential Isaria sinclairii, a traditional Chinese medicine
      composed of the fruiting bodies of I. sinclairii and its parasitic host larva,
      was evaluated using short-term genotoxicity tests, namely, the Ames test,
      chromosome aberration (CA), and micronuclei (MN) tests. In a Salmonella
      typhimurium assay, I. sinclairii extract (ISE) did not produce any mutagenic
      response in the absence or presence of 59 mix with TA98, TA100, TA1535, and
      TA1537. In the chromosome aberration (CA) test, ISE induced no significant effect
      on Chinese hamster ovary (CHO) cells compared with control. In the MN test, no
      significant change in the occurrence of micronucleated polychromatic erythrocytes
      was observed in male ICR mice intraperitoneally administered ISE at doses of 15,
      150, or 1500 mg/kg. These results indicate that ISE has no mutagenic potential in
      these in vitro and in vivo systems.

PMID- 15513902
TI  - Neonatal exposure to di(n-butyl) phthalate (DBP) alters male reproductive-tract
      development.
AB  - The purpose of this study was to evaluate male reproductive-organ development in
      early postnatal male rats following neonatal exposure to di(n-butyl) phthalate
      (DBP) and identify a mechanism of action. Neonatal male rats were injected
      subcutaneously from d 5 to 14 after birth with corn oil (control) and DBP (5, 10,
      or 20 mg/animal). Animals were killed at postnatal day (PND) 31 and PND 42,
      respectively, and testes, epididymis, seminal vesicles, ventral prostate, levator
      ani plus bulbocavernosus muscles (LABC), and Cowper's glands were weighed. In
      addition, the expressions of androgen receptor (AR), estrogen receptors (ERs),
      and steroidogenic factor-1 (SF-1) were also examined in the testes. Total body
      weights gains were significantly reduced at PND 29-31, but gradually recovered on
      PND 42. However, DBP (20 mg/animal) significantly reduced the weights of testes
      and accessory sex organs (seminal vesicles, LABC, and Cowper's glands), but not
      of the epididymis. These adverse effects persisted through puberty at PND 42.
      Serum testosterone levels did not show any significant changes in the control and
      DBP treatment groups. Histomorphological examination showed mild diffuse Leydig
      cell hyperplasia in the interstitium of severely affected tubules on PND 31. Only
      a few multinuclear germ cells were observed. DBP (20 mg/animal) significantly
      decreased the expression of AR, whereas ER expression and SF-1 expression were
      increased in a dose-dependent manner on PND 31 in the rat testes. On PND 42, DBP
      (20 mg/animal) significantly inhibited ER expression in the testes, but not AR,
      ER, and SF-1. These results demonstrate that neonatal exposure to DBP produces
      permanent changes in the endocrine system and leads to abnormal male reproductive
      tract development until puberty. Thus our data suggest that DBP is likely to
      exert its antiandrogenic actions through disruption of AR or ER expression during
      the early neonatal stage.

PMID- 15513903
TI  - Cytochrome p-450-mediated differential oxidative modification of proteins:
      albumin, apolipoprotein E, and CYP2E1 as targets.
AB  - Although many studies established a role of cytochrome P-450s in metabolism of
      xenobiotics, few studies evaluating the ability of cytochrome P-450s to oxidize
      proteins have been reported. The ability of cytochrome P-450s to induce oxidative
      modification of albumin, apolipoprotein E, and CYP2E1 protein was investigated.
      Microsomal cytochrome P-450s induced production of reactive radical species,
      leading to differential modification of the proteins. Albumin remained
      unmodified, and CYP2E1 protein was degraded, whereas recombinant and endogenous
      apolipoprotein E was aggregated. The modification of apolipoprotein E was isoform
      independent. Cytochrome P-450 inhibitors or antioxidants inhibited the production
      of reactive radical species and protein modification. These results demonstrate
      that response of each protein to cytochrome P-450-mediated oxidative attack is
      different, and cytochrome P-450s can induce apolipoprotein E aggregation, a
      process that might be relevant to accumulation of altered protein in various
      abnormal conditions. In view of the ubiquitous expression of cytochrome P-450s,
      the present results may have important toxicological implications.

PMID- 15513904
TI  - Differential gene profiles in developing embryo and fetus after in utero exposure
      to ethanol.
AB  - Alcohol consumption during pregnancy results in morphological abnormalities in
      the fetuses of humans and experimental animals, and is referred to as fetal
      alcohol syndrome (FAS). However, the molecular mechanism underlying FAS has not
      been completely elucidated. The aim of the present study was to investigate the
      potential molecular mechanisms of ethanol-induced FAS in the developing embryo
      and fetus. cDNA microarray analysis was used to screen for altered gene profiles.
      Ethanol at a teratogenic dosage (3.8 g/kg, twice a day) was administered
      intraperitoneally to pregnant C57Bl/6J mice from gestation day (GD) 6 to 8.
      Morphologic observations showed excessive malformations of the craniofacial
      regions (reduction of the face, the absence of eyes, nose, jaw, and mandible,
      underdevelopment of vibrissae areas, cleft lip, and palate) in ethanol-exposed
      embryos (GD 10) and fetusus (GD 15). cDNA microarray analysis showed alterations
      in several gene profiles, including the "palate, lung, and nasal epithelium clone
      (plunc), "neurofilament, " and "pale ear. " Of these genes, the expressions of
      plunc were confirmed by reverse-transcription polymerase chain reaction (RT-PCR)
      and whole-mount in situ hybridization. The plunc was highly expressed in the
      craniofacial region, specifically in upper airways and nasopharyngeal epithelium.
      RT-PCR analysis revealed that normal plunc mRNA expression levels were present in
      GD 15 fetuses, but not in GD 10 embryos. Interestingly, ethanol significantly
      downregulated the plunc expression in GD 15 fetuses. Our results suggest that
      ethanol-induced FAS is due in part to the downregulation of plunc expression in
      the fetus, and this gene may be a candidate biological marker for FAS.

PMID- 15513905
TI  - Altered de novo sphingolipid biosynthesis is involved in the serum deprivation
      induced cell death in LLC-PK1 cells.
AB  - Fumonisin B1, a specific inhibitor of ceramide synthase, and ISPI (Myriocin), a
      serine palmitoyltransferase inhibitor, modulate the de novo sphingolipid
      biosynthesis pathway. This study was conducted to determine whether serum
      deprivation-induced cell death is regulated by de novo sphingolipid biosynthesis
      in pig kidney LLC-PK1 cells. Serum withdrawal from the culture medium produced
      cell death in LLC-PK1 cells. Fumonisin B1 at concentrations ranging from 5 M to
      30 M delayed until 48 h this cell death resulting from the absence of fetal
      bovine serum (FBS) in cell culture. Pretreatment of cultured cells with fumonisin
      B1 in the presence of serum for 24 h increased by approximately 70% this
      cytoprotective activity of fumonisin B1 against serum deprivation-induced cell
      death. Serum deprivation increased sphingolipid biosynthesis threefold compared
      to 5% serum-enriched culture. Fumonisin B1 at 5-30 M lowered the content of total
      complex sphingolipids to levels of 50% and 77% of the content in serum-enriched
      culture, although the concentration of intracellular free sphinganine was
      elevated. ISP1 alone at greater than 1 nM concentration reduced total complex
      sphingolipid content to values in LLC-PK1 cells grown in the presence of 5% FBS.
      The results suggest that the de novo complex sphingolipid biosynthesis modulated
      by either fumonisin B1 or ISP1 may regulate serum deprivation-induced cell death
      in LLC-PK1 cells.

PMID- 15513907
TI  - Ferruginous bodies: implications in the mechanism of fiber and particle toxicity.
AB  - Exposures to fibers and particles can be associated with several different lung
      injuries including bronchitis, bronchiolitis, pneumonitis, pleuritis, pulmonary
      alveolar proteinosis, pneumoconiosis, mesotheliomas, and lung cancers. The
      mechanism of biological effect exerted by fibers and particles has not been
      exactly defined. Exposures to all fibers and particles introduce a solid-liquid
      interface into the lower respiratory tract. These surfaces all have some
      concentration of oxygen-containing functional groups that demonstrate a capacity
      to coordinate iron. Radical generation is catalyzed by this metal resulting in a
      cascade of cell signaling, transcription factor activation, and mediator release.
      We propose that the ferruginous body (i.e., a fiber or particle with a coating of
      both protein and iron) provides direct evidence of a participation of iron in the
      biological effect of both fibers and particles. It is recommended that an
      identification of ferruginous bodies in the lung be regarded as support for a
      metal-catalyzed oxidative stress in the mechanism of cell and tissue injury.

PMID- 15513908
TI  - Brain inflammation and Alzheimer's-like pathology in individuals exposed to
      severe air pollution.
AB  - Air pollution is a complex mixture of gases (e.g., ozone), particulate matter,
      and organic compounds present in outdoor and indoor air. Dogs exposed to severe
      air pollution exhibit chronic inflammation and acceleration of Alzheimer's-like
      pathology, suggesting that the brain is adversely affected by pollutants. We
      investigated whether residency in cities with high levels of air pollution is
      associated with human brain inflammation. Expression of cyclooxygenase-2 (COX2),
      an inflammatory mediator, and accumulation of the 42-amino acid form of beta
      amyloid (Abeta42), a cause of neuronal dysfunction, were measured in autopsy
      brain tissues of cognitively and neurologically intact lifelong residents of
      cities having low (n:9) or high (n:10) levels of air pollution. Genomic DNA
      apurinic/apyrimidinic sites, nuclear factor-kappaB activation and apolipoprotein
      E genotype were also evaluated. Residents of cities with severe air pollution had
      significantly higher COX2 expression in frontal cortex and hippocampus and
      greater neuronal and astrocytic accumulation of Abeta42 compared to residents in
      low air pollution cities. Increased COX2 expression and Abeta42 accumulation were
      also observed in the olfactory bulb. These findings suggest that exposure to
      severe air pollution is associated with brain inflammation and Abeta42
      accumulation, two causes of neuronal dysfunction that precede the appearance of
      neuritic plaques and neurofibrillary tangles, hallmarks of Alzheimer's disease.

PMID- 15513909
TI  - Indole-3-acetic acid induces microencephaly in rat fetuses.
AB  - Indole-3-acetic acid (IAA), known as natural auxin, induces cleft palate in
      rodents. However, there has been no report about the neurodevelopmental toxicity
      of IAA in rats. In the present study, we found microencephaly in the fetuses from
      the rats exposed to IAA. The purpose of this work was to examine the effects of
      IAA administration in pregnant rats on neuroepithelial cells in the
      embryos/fetuses. IAA was administered at 500 and 1,000 mg/kg on gestation days
      (days) 12, 13, and 14, and then embryos/fetuses were harvested on days 14.5, 15,
      16, and 21. Cleft palate was induced at 1,000 mg/kg. The brain in treated groups
      exhibited reduction in the size and weight on day 21 in a dose-dependent manner.
      Histopathologically, apoptotic cells were observed mainly in the medial and
      dorsal layer of the neuroepithelium at 500 and 1,000 mg/kg on day 14.5. On day
      15, they were observed in the medial and dorsal layer of the neuroepithelium, and
      preplate at 1,000 mg/kg. On day 16, they existed in the dorsal layer of the
      neuroepithelium and intermediate zone in the embryos from 1 dam at 1,000 mg/kg.
      On day 21, an increase in cell proliferative activity was observed in the
      neuroepithelium at 500 and 1,000 mg/kg. The reduction of the cortical plate, the
      enlargement of the neuroepithelium and a slight increase in neuron density in the
      intermediate zone were observed at 1,000 mg/kg. These findings indicated IAA
      might induce the neuronal apoptosis in the S phase and lead to microencephaly.

PMID- 15513910
TI  - Progression of chronic hepatitis and preneoplasia in Helicobacter hepaticus
      infected A/JCr mice.
AB  - Helicobacter hepaticus infection induces sustained inflammation and carcinoma of
      the liver in A/JCr mice, and serves as a model of human cancers associated with
      viral hepatitis and H. pylorichronic gastritis. Here we describe the pathogenesis
      of premalignant disease in A/JCr mice infected with H. hepaticus. We inoculated
      dams intragestationally and/or pups postnatally, and evaluated offspring at 3, 6,
      or 12 months. Mice infected at or before 3 weeks of age, but not at 12 weeks,
      developed disease. Male mice were most affected, but expressed a bimodal pattern
      of susceptibility. Males exhibited lobular necrogranulomatous and interface
      (chronic active) hepatitis, while females usually developed intraportal (chronic
      persistent) hepatitis. Portal inflammation was slowly progressive, with tertiary
      lymphoid nodule development by 12 months. Hepatic bacterial load and
      preneoplastic lesions, including clear and tigroid cell foci of cellular
      alteration, were correlated with lobular hepatitis severity. No extrahepatic
      surrogate disease marker reliably predicted individual hepatitis grade. In
      conclusion, gender and bacterial exposure timing are key determinants of H.
      hepaticus disease outcomes. Intrahepatic inflammation is driven by local signals
      characterized by a vigorous but nonsterilizing immune response. Continued study
      of chronic hepatitis progression may reveal therapeutic targets to reduce the
      risk of hepatocellular carcinoma.

PMID- 15513911
TI  - Hepatic temporal gene expression profiling in Helicobacter hepaticus-infected
      A/JCr mice.
AB  - Helicobacter hepaticus infection of A/JCr mice is a model of infectious liver
      cancer. We monitored hepatic global gene expression profiles in H. hepaticus
      infected and control male A/JCr mice at 3 months, 6 months, and 1 year of age
      using an Affymetrix-based oligonucleotide microarray platform on the premise that
      a specific genetic expression signature at isolated time points would be
      indicative of disease status. Model based expression index comparisons generated
      by dChip yielded consistent profiles of differential gene expression for H.
      hepaticus infected male mice with progressive liver disease versus uninfected
      control mice within each age group. Linear discriminant analysis and principal
      component analysis allowed segregation of mice based on combined age and lesion
      status, or age alone. Up-regulation of putative tumor markers correlated with
      advancing hepatocellular dysplasia. Transcriptionally down-regulated genes in
      mice with liver lesions included those related to peroxisome proliferator, fatty
      acid, and steroid metabolism pathways. In conclusion, transcriptional profiling
      of hepatic genes documented gene expression signatures in the livers of H.
      hepaticus infected male A/JCr mice with chronic progressive hepatitis and
      preneoplastic liver lesions, complemented the histopathological diagnosis, and
      suggested molecular targets for the monitoring and intervention of disease
      progression prior to the onset of hepatocellular neoplasia.

PMID- 15513913
TI  - CcmD is involved in complex formation between CcmC and the heme chaperone CcmE
      during cytochrome c maturation.
AB  - CcmD is a small membrane protein involved in heme delivery to the heme chaperone
      CcmE during cytochrome c maturation. Here we show that it physically interacts
      with CcmE and CcmC, another essential component of the heme delivery system. We
      demonstrate the formation of a ternary complex consisting of CcmCDE. A deletion
      analysis of individual domains revealed that the central hydrophobic domain is
      essential for its function. Moreover, the C-terminal, cytoplasmic domain seems to
      require a net positive charge to be functional. Our topology analysis indicates
      that CcmD is an integral interfacial membrane protein with its N and C termini
      extruding into the cytoplasmic side of the membrane. Interactions of CcmD with
      either ferrochelatase, the last heme biosynthetic enzyme, or directly with heme
      were not detectable. We postulate a function for CcmD in protein-protein
      interaction or membrane protein assembly required for the heme delivery process.

PMID- 15513914
TI  - Temporins, small antimicrobial peptides with leishmanicidal activity.
AB  - Leishmaniasis encompasses a wide range of infections caused by the human
      parasitic protozoan species belonging to the Leishmania genus. It appears
      frequently as an opportunistic disease, especially in virus-infected
      immunodepressed people. Similarly to other pathogens, parasites became resistant
      to most of the first-line drugs. Therefore, there is an urgent need to develop
      antiparasitic agents with new modes of action. Gene-encoded antimicrobial
      peptides are promising candidates, but so far only a few of them have shown anti
      protozoa activities. Here we found that temporins A and B, 13-amino acid
      antimicrobial peptides secreted from the skin of the European red frog Rana
      temporaria, display anti-Leishmania activity at micromolar concentrations, with
      no cytolytic activity against human erythrocytes. To the best of our knowledge,
      temporins represent the shortest natural peptides having the highest
      leishmanicidal activity and the lowest number of positively charged amino acids
      (a single lysine/arginine) and maintain biological function in serum. Their
      lethal mechanism involves plasma membrane permeation based on the following data.
      (i) They induce a rapid collapse of the plasma membrane potential. (ii) They
      induce the influx of the vital dye SYTOX Green. (iii) They reduce intracellular
      ATP levels. (iv) They severely damage the membrane of the parasite, as shown by
      transmission electron microscopy. Besides giving us basic important information,
      the unique properties of temporins, as well as their membranolytic effect, which
      should make it difficult for the pathogen to develop resistance, suggest them as
      potential candidates for the future design of antiparasitic drugs with a new mode
      of action.

PMID- 15513912
TI  - Direct cell cycle regulation by the fibroblast growth factor receptor (FGFR)
      kinase through phosphorylation-dependent release of Cks1 from FGFR substrate 2.
AB  - Fibroblast growth factors (FGFs) are upstream activators of the mitogen-activated
      protein kinase pathway and mitogens in a wide variety of cells. However, whether
      the mitogen-activated protein kinase pathway solely accounts for the induction of
      cell cycle or antiapoptotic activity of the FGF receptor (FGFR) tyrosine kinase
      is not clear. Here we report that cell cycle inducer Cks1, which triggers
      ubiquitination and degradation of p27(Kip1), associates with the unphosphorylated
      form of FGFR substrate 2 (FRS2), an adaptor protein that is phosphorylated by
      FGFR kinases and recruits downstream signaling molecules. FGF-dependent
      activation of FGFR tyrosine kinases induces FRS2 phosphorylation, causes release
      of Cks1 from FRS2, and promotes degradation of p27(Kip1) in 3T3 cells. Since
      degradation of p27(Kip1) is a key regulatory step in activation of the cyclin E/A
      Cdk complex during the G(1)/S transition of the cell cycle, the results suggest a
      novel mitogenic pathway whereby FGF and other growth factors that activate FRS2
      directly activate cyclin-dependent kinases.

PMID- 15513915
TI  - Neurotrophin-dependent tyrosine phosphorylation of Ras guanine-releasing factor 1
      and associated neurite outgrowth is dependent on the HIKE domain of TrkA.
AB  - Ras guanine-releasing factor 1 (RasGrf1), a guanine nucleotide exchange factor
      for members of the Ras and Rho family of GTPases, is highly expressed in the
      brain. It is regulated by two separate mechanisms, calcium regulation through
      interaction with its calcium/calmodulin-binding IQ domain and serine and tyrosine
      phosphorylation. RasGrf1 is activated downstream of G-protein-coupled receptors
      and the non-receptor tyrosine kinases, Src and Ack1. Previously, we demonstrated
      a novel interaction between the intracellular domain of the nerve growth factor
      regulated TrkA receptor tyrosine kinase and an N-terminal fragment of RasGrf1. We
      now show that RasGrf1 is phosphorylated and interacts with TrkA, -B, and -C in co
      transfection studies. This interaction and phosphorylation of RasGrf1 is
      dependent on the HIKE domain of TrkA (a region shown to interact with pleckstrin
      homology domains) but not on any of the phosphotyrosine residues that act as
      docking sites for intracellular signaling molecules such as Shc and FRS-2. The
      PH1 domain alone of RasGrf1 is sufficient for phosphorylation by the TrkA
      receptor. A potential role for Trk activation of RasGrf1 is suggested through
      transfection studies in PC12 cells in which RasGrf1 significantly increases
      neurite outgrowth at low doses of neurotrophin stimulation. Notably, this neurite
      outgrowth is dependent on an intact HIKE domain, as nnr5-S10 cells expressing a
      TrkA HIKE domain mutant do not exhibit potentiated neurite outgrowth in the
      presence of RasGrf1. These studies identify RasGrf1 as a novel target of
      neurotrophin activation and suggest an additional pathway whereby neurotrophin
      stimulated neurite outgrowth may be regulated.

PMID- 15513916
TI  - Evidence that the plastid translocon Tic40 components possess modulating
      capabilities.
AB  - The transport of proteins into the plastid is a process that faces changing
      cellular needs such as the situation found in different plant organs or
      developing tissues. The plastid translocon must therefore be responsive to the
      changing cell environment to deliver efficiently different arrays of structurally
      diverse proteins. Although the Tic40-related envelope proteins appear to be
      translocon components designed to address the varying needs of protein
      translocation, details of their involvement remain elusive. This study was thus
      designed to combine plant-based experiments and yeast mitochondrion-based
      approaches for unveiling clues related to how the Tic40 components may behave
      during the protein translocation process. The main findings related to how Tic40
      proteins may work are: 1) natural fluctuations are apparent in developing
      tissues, in different organs of the same plant, and in different species; 2)
      transgenic Arabidopsis seedlings can tolerate functionally a wide range of
      variations in Tic40 levels, from partial suppression to excessive production; 3)
      the Tic40 proteins themselves exhibit configurational changes in their
      association with yeast mitochondria in response to different carbon sources; 4)
      the presence of Tic40 proteins in yeast mitochondria influences regulatory
      aspects of the mitochondrial translocon; and 5) the Tic40 proteins associate with
      mitochondrial translocon components involved in regulatory-like events. The
      combined data provide evidence that Tic40 proteins possess modulating
      capabilities.

PMID- 15513917
TI  - Parathyroid hormone uses multiple mechanisms to arrest the cell cycle progression
      of osteoblastic cells from G1 to S phase.
AB  - Parathyroid hormone (PTH) plays a major role in bone remodeling and has the
      ability to increase bone mass if administered daily. In vitro, PTH inhibits the
      growth of osteoblastic cell lines, arresting them in G(1) phase. Here, we
      demonstrate that PTH regulates the expression of at least three genes to achieve
      the following: inducing expression of MAPK phosphatase 1 (MKP-1) and p21(Cip1)
      and decreasing expression of cyclin D1 at both mRNA and protein levels. The
      induction of MKP-1 causes the dephosphorylation of extracellular signal-regulated
      kinase and therefore the decrease in cyclin D1. Overexpression of MKP-1 arrests
      UMR cells in G(1) phase. The mechanisms involved in PTH regulation of these genes
      were studied. Most importantly, PTH administration produces similar effects on
      expression of these genes in rat femoral metaphyseal primary spongiosa. Analyses
      of p21(Cip1) expression levels in bone indicate that repeated daily PTH
      injections make the osteoblast more sensitive to successive PTH treatments, and
      this might be an important feature for the anabolic functions of PTH. In summary,
      our data suggest that one mechanism for PTH to exert its anabolic effect is to
      arrest the cell cycle progression of the osteoblast and hence increase its
      differentiation.

PMID- 15513918
TI  - The role of Plasmodium falciparum food vacuole plasmepsins.
AB  - Plasmepsins (PMs) are thought to have an important function in hemoglobin
      degradation in the malarial parasite Plasmodium falciparum and have generated
      interest as antimalarial drug targets. Four paralogous plasmepsins reside in the
      food vacuole of P. falciparum. Targeted gene disruption by double crossover
      homologous recombination has been employed to study food vacuole plasmepsin
      function in cultured parasites. Parasite clones with deletions in each of the
      individual PM I, PM II, and HAP genes as well as clones with a double PM IV/PM I
      disruption have been generated. All of these clones lack the corresponding PMs,
      are viable, and appear morphologically normal. PM II and PM IV/I disruptions have
      longer doubling times than the 3D7 parental line in rich RPMI medium. This
      appears to be because of a decreased level of productive progeny rather than an
      increased cell cycle time. In amino acid-limited medium, all four knockouts
      exhibit slower growth than the parental strain. Compared with 3D7, knock-out
      clone sensitivity to aspartic and cysteine protease inhibitors is changed
      minimally. These results suggest substantial functional redundancy and have
      important implications for the design of antimalarial drugs. The slow growth
      phenotype may explain why P. falciparum has maintained four plasmepsin genes with
      overlapping functions.

PMID- 15513919
TI  - Trapping prion protein in the endoplasmic reticulum impairs PrPC maturation and
      prevents PrPSc accumulation.
AB  - The conversion of the normal cellular prion protein (PrP(C)) into the abnormal
      scrapie isoform (PrP(Sc)) is a key feature of prion diseases. The pathogenic
      mechanisms and the subcellular sites of the conversion are complex and not
      completely understood. In particular, little is known on the role of the early
      compartment of the secretory pathway in the processing of PrP(C) and in the
      pathogenesis of prion diseases. In order to interfere with the intracellular
      traffic of endogenous PrP(C) we have generated two anti-prion single chain
      antibody fragments (scFv) directed against different epitopes, each fragment
      tagged either with a secretory leader or with the ER retention signal KDEL. The
      stable expression of these constructs in PC12 cells allowed us to study their
      specific effects on the synthesis, maturation, and processing of endogenous
      PrP(C) and on PrP(Sc) formation. We found that ER-targeted anti-prion scFvs
      retain PrP(C) in the ER and inhibit its translocation to the cell surface.
      Retention in the ER strongly affects the maturation and glycosylation state of
      PrP(C), with the appearance of a new aberrant endo-H sensitive glycosylated
      species. Interestingly, ER-trapped PrP(C) acquires detergent insolubility and
      proteinase K resistance. Furthermore, we show that ER-targeted anti-prion
      antibodies prevent PrP(Sc) accumulation in nerve growth factor-differentiated
      PC12 cells, providing a new tool to study the molecular pathology of prion
      diseases.

PMID- 15513920
TI  - Early painful diabetic neuropathy is associated with differential changes in the
      expression and function of vanilloid receptor 1.
AB  - Diabetes mellitus is associated with one or more kinds of stimulus-evoked pain
      including hyperalgesia and allodynia. The mechanisms underlying painful diabetic
      neuropathy remain poorly understood. Previous studies demonstrate an important
      role of vanilloid receptor 1 (VR1) in inflammation and injury-induced pain. Here
      we investigated the function and expression of VR1 in dorsal root ganglion (DRG)
      neurons isolated from streptozotocin-induced diabetic rats between 4 and 8 weeks
      after onset of diabetes. DRG neurons from diabetic rats showed significant
      increases in capsaicin- and proton-activated inward currents. These evoked
      currents were completely blocked by the capsaicin antagonist capsazepine.
      Capsaicin-induced desensitization of VR1 was down-regulated, whereas VR1 re
      sensitization was up-regulated in DRG neurons from diabetic rats. The protein
      kinase C (PKC) activator phorbol 12-myristate 13-acetate blunted VR1
      desensitization, and this effect was reversible in the presence of the PKC
      inhibitor bisindolylmaleimide I. Compared with the controls, VR1 protein was
      decreased in DRG whole-cell homogenates from diabetic rats, but increased levels
      of VR1 protein were observed on plasma membranes. Of interest, the tetrameric
      form of VR1 increased significantly in DRGs from diabetic rats. Increased
      phosphorylation levels of VR1 were also observed in DRG neurons from diabetic
      rats. Colocalization studies demonstrated that VR1 expression was increased in
      large myelinated A-fiber DRG neurons, whereas it was decreased in small
      unmyelinated C-fiber neurons as a result of diabetes. These results suggest that
      painful diabetic neuropathy is associated with altered cell-specific expression
      of the VR1 receptor that is coupled to increased function through PKC-mediated
      phosphorylation, oligomerization, and targeted expression on the cell surface
      membrane.

PMID- 15513921
TI  - Amyloid fibril formation from sequences of a natural beta-structured fibrous
      protein, the adenovirus fiber.
AB  - Amyloid fibrils are fibrous beta-structures that derive from abnormal folding and
      assembly of peptides and proteins. Despite a wealth of structural studies on
      amyloids, the nature of the amyloid structure remains elusive; possible
      connections to natural, beta-structured fibrous motifs have been suggested. In
      this work we focus on understanding amyloid structure and formation from
      sequences of a natural, beta-structured fibrous protein. We show that short
      peptides (25 to 6 amino acids) corresponding to repetitive sequences from the
      adenovirus fiber shaft have an intrinsic capacity to form amyloid fibrils as
      judged by electron microscopy, Congo Red binding, infrared spectroscopy, and x
      ray fiber diffraction. In the presence of the globular C-terminal domain of the
      protein that acts as a trimerization motif, the shaft sequences adopt a triple
      stranded, beta-fibrous motif. We discuss the possible structure and arrangement
      of these sequences within the amyloid fibril, as compared with the one adopted
      within the native structure. A 6-amino acid peptide, corresponding to the last
      beta-strand of the shaft, was found to be sufficient to form amyloid fibrils.
      Structural analysis of these amyloid fibrils suggests that perpendicular stacking
      of beta-strand repeat units is an underlying common feature of amyloid formation.

PMID- 15513922
TI  - Cadmium inhibits the functions of eukaryotic MutS complexes.
AB  - Exposure of yeast cells to low concentrations of cadmium results in elevated
      mutation rates due to loss of mismatch repair (MMR), and cadmium inhibits MMR
      activity in extracts of human cells. Here we show that cadmium inhibits both Msh2
      Msh6- and Msh2-Msh3-dependent human MMR activity in vitro. This inhibition, which
      occurs at a step or steps preceding repair DNA synthesis, is observed for repair
      directed by either a 3' or a 5' nick. In an attempt to identify the protein
      target(s) of cadmium inhibition, we show that cadmium inhibition of MMR is not
      reversed by addition of zinc to the repair reaction, suggesting that the target
      is not a zinc metalloprotein. We then show that cadmium inhibits ATP hydrolysis
      by yeast Msh2-Msh6 but has no effect on ATPase hydrolysis by yeast Mlh1-Pms1.
      Steady state kinetic analysis with wild type Msh2-Msh6, and with heterodimers
      containing subunit-specific Glu to Ala replacements inferred to inactivate the
      ATPase activity of either Msh2 or Msh6, suggest that cadmium inhibits ATP
      hydrolysis by Msh6 but not Msh2. Cadmium also reduces DNA binding by Msh2-Msh6
      and more so for mismatched than matched duplexes. These data indicate that
      eukaryotic Msh2-Msh3 and Msh2-Msh6 complexes are targets for inhibition of MMR by
      cadmium, a human lung carcinogen that is ubiquitous in the environment.

PMID- 15513923
TI  - C-terminal sequences direct cyclin D1-CRM1 binding.
AB  - GSK-3beta-dependent phosphorylation of cyclin D1 at a conserved C-terminal
      residue, Thr-286, promotes CRM1-dependent cyclin D1 nuclear export. Herein, we
      have identified a short stretch of residues adjacent to Thr-286 that mediates
      CRM1 association and thus cyclin D1 nuclear export. We found that disruption of
      this hydrophobic patch, stretching from amino acids 290 to 295 within cyclin D1,
      results in constitutively nuclear cyclin D1-CDK4 complexes with an increased
      propensity to potentiate transformation of murine fibroblasts. Our data support a
      model wherein deregulation of cyclin D1 nuclear export might contribute to human
      neoplastic growth.

PMID- 15513924
TI  - Endothelin 1 induces beta 1Pix translocation and Cdc42 activation via protein
      kinase A-dependent pathway.
AB  - p21-activated kinase (Pak)-interacting exchange factor (Pix), a Rho family
      guanine nucleotide exchange factor (GEF), has been shown to co-localize with Pak
      and form activated Cdc42- and Rac1-driven focal complexes. In this study we have
      presented evidence that treatment of human mesangial cells (HMC) with endothelin
      1 (ET-1) and stimulation of adenylate cyclase with either forskolin or with the
      cAMP analog 8-Br-cAMP activated the GTP loading of Cdc42. Transient expression of
      constitutively active G alpha(s) also stimulated Cdc42. In addition,
      overexpression of beta(1)Pix enhanced ET-1-induced Cdc42 activation, whereas the
      expression of beta(1)Pix SH3m(W43K), which lacks the ability to bind Pak, and
      beta(1)PixDHm(L238R/L239S), which lacks GEF activity, decreased ET-1-induced
      Cdc42 activation. Furthermore, ET-1 stimulation induced beta(1)Pix translocation
      to focal complexes. Interestingly, pretreatment of HMC with protein kinase A
      (PKA) inhibitors blocked both Cdc42 activation and beta(1)Pix translocation
      induced by ET-1, indicating the involvement of the PKA pathway. Through site
      directed mutagenesis studies of consensus PKA phosphorylation sites and in vitro
      PKA kinase assay, we have shown that beta(1)Pix is phosphorylated by PKA. Using
      purified recombinant beta(1)Pix(wt) and beta(1)Pix mutants, we have identified
      Ser-516 and Thr-526 as the major phosphorylation sites by PKA.
      beta(1)Pix(S516A/T526A), in which both phosphorylation sites are replaced by
      alanine, blocks beta(1)Pix translocation and Cdc42 activation. Our results have
      provided evidence that stimulation of PKA pathway by ET-1 or cAMP analog results
      in beta(1)Pix phosphorylation, which in turn controls beta(1)Pix translocation to
      focal complexes and Cdc42 activation.

PMID- 15513925
TI  - Depletion of apolipoprotein N-acyltransferase causes mislocalization of outer
      membrane lipoproteins in Escherichia coli.
AB  - Lipoproteins in Gram-negative Enterobacteriaceae carry three fatty acids on the N
      terminal cysteine residue, two as a diacylglyceride and one through an N-linkage
      following signal peptide cleavage. Most lipoproteins are anchored in the outer
      membrane, facing the periplasm, but some lipoproteins remain in the plasma
      membrane, depending on the amino acid at position +2, immediately after the fatty
      acylated cysteine. In vitro, the last step in lipoprotein maturation, N-acylation
      of apolipoproteins by the plasma membrane apolipoprotein N-acyltransferase (Lnt),
      is necessary for efficient recognition of outer membrane lipoproteins by the Lol
      system, which transports them from the plasma to the outer membrane (Fukuda, A.,
      Matsuyama, S.-I., Hara, T., Nakayama, J., Nagasawa, H., and Tokuda, H. (2002) J.
      Biol. Chem. 277, 43512-43518). To study the role of Lnt in vivo, we constructed a
      conditional lnt mutant of Escherichia coli. The apo-form of peptidoglycan
      anchored major lipoprotein (Lpp) and two other outer membrane lipoproteins
      accumulated in the plasma membrane when lnt expression was reduced. We also found
      that Lnt is an essential protein in E. coli and that the lethality is partially
      because of the retention of apoLpp in the plasma membrane. Topology mapping of
      Lnt with beta-galactosidase and alkaline phosphatase fusions indicated the
      presence of six membrane-spanning segments. The lnt gene in a mutant of
      Salmonella enterica displaying thermosensitive Lnt activity (Gupta, S. D., Gan,
      K., Schmid, M. B., and Wu, H. C. (1993) J. Biol. Chem. 268, 16551-16556) was
      found to carry a mutation causing a single glutamate to lysine substitution at a
      highly conserved position in the last predicted periplasmic loop of the protein.

PMID- 15513926
TI  - Uncoupling of inhibitory and shuttling functions of rho GDP dissociation
      inhibitors.
AB  - Rho GDP dissociation inhibitors (rhoGDIs) are postulated to regulate the activity
      of small G proteins of the Rho family by a shuttling process involving the
      extraction of Rho from donor membranes, the formation of the inhibitory cytosolic
      Rho/rhoGDI complexes, and delivery of Rho to target membranes. However, the role
      of rhoGDIs in site-specific membrane targeting or extraction of Rho is still
      poorly understood. Here we investigated the molecular functions of two rhoGDIs,
      the specific rhoGDI-3 and the less specific but well studied rhoGDI-1, in HeLa
      cells using structure-based mutagenesis of the rhoGDI protein. We identified two
      sites in rhoGDI, which form conserved interactions with their Rho target, whose
      mutation results in the uncoupling of inhibitory and shuttling functions of
      rhoGDIs: D66GDI-3 (equivalent to D45GDI-1), a conserved residue in the helix-loop
      helixGDI/switch 1Rho interface, and D206GDI-3 (equivalent to D185GDI-1) in the
      beta-sandwichGDI/switch 2Rho interface. Mutations of both sites result in the
      loss of rhoGDI-3 or rhoGDI-1 inhibitory activity but not of their ability to form
      cytosolic complexes with RhoG or Cdc42 in vivo. Remarkably, the mutants were
      detected at Rho-induced membrane ruffles or protrusions where they co-localized
      with RhoG or Cdc42, likely identifying for the first time the site of extraction
      of a Rho protein by a rhoGDI in vivo. We propose that these mutations act by
      modifying the steady-state kinetics of the shuttling process regulated by
      rhoGDIs, such that transient steps at the cell membranes now become detectable.
      They should provide valuable tools for future investigations of the dynamics of
      membrane extraction or delivery of Rho proteins and their regulation by cellular
      partners.

PMID- 15513927
TI  - Conformational flexibility in crystal structures of human 11beta-hydroxysteroid
      dehydrogenase type I provide insights into glucocorticoid interconversion and
      enzyme regulation.
AB  - Human 11beta-hydroxysteroid dehydrogenase type I (11beta-HSD1) is an ER-localized
      membrane protein that catalyzes the interconversion of cortisone and cortisol. In
      adipose tissue, excessive cortisol production through 11beta-HSD1 activity has
      been implicated in the pathogenesis of type II diabetes and obesity. We report
      here biophysical, kinetic, mutagenesis, and structural data on two ternary
      complexes of 11beta-HSD1. The combined results reveal flexible active site
      interactions relevant to glucocorticoid recognition and demonstrate how four
      11beta-HSD1 C termini converge to form an as yet uncharacterized tetramerization
      motif. A C-terminal Pro-Cys motif is localized at the center of the tetramer and
      forms reversible enzyme disulfides that alter enzyme activity. Conformational
      flexibility at the tetramerization interface is coupled to structural changes at
      the enzyme active site suggesting how the central Pro-Cys motif may regulate
      enzyme activity. Together, the crystallographic and biophysical data provide a
      structural framework for understanding 11beta-HSD1 activities and will ultimately
      facilitate the development of specific inhibitors.

PMID- 15513928
TI  - A structural basis of Equisetum arvense ferredoxin isoform II producing an
      alternative electron transfer with ferredoxin-NADP+ reductase.
AB  - We have determined the crystal structure, at 1.2-A resolution, of Equisetum
      arvense ferredoxin isoform II (FdII), which lacks residues equivalent to Arg(39)
      and Glu(28) highly conserved among other ferredoxins (Fds). In other Fds these
      residues form an intramolecular salt bridge crucial for stabilization of the [2Fe
      2S] cluster, which is disrupted upon complex formation with Fd-NADP(+)
      oxidoreductase (FNR) to form two intermolecular salt bridges. The overall
      structure of FdII resembles the known backbone structures of E. arvense isoform I
      (FdI) and other plant-type Fds. Dramatically, in the FdII structure a unique,
      alternative salt bridge is formed between Arg(22) and Glu(58). This results in a
      different relative orientation of the alpha-helix formed by Leu(23)-Glu(29) and
      eliminates the possibility of forming three of the five intermolecular salt
      bridges identified on formation of a complex between maize FdI and maize FNR.
      Mutation of FdII, informed by structural differences with FdI, showed that the
      alternative salt bridge and the absence of an otherwise conserved Tyr residue are
      important for the alternative stabilization of the FdII [2Fe-2S] cluster. We also
      investigated FdI and FdII electron transfer to FNR on chloroplast thylakoid
      membranes. The K(m) and V(max) values of FdII are similar to those of FdI,
      contrary to previous measurements of the reverse reaction, from FNR to Fd. The
      affinity between reduced FdI and oxidized FNR is much greater than that between
      oxidized FdI and reduced FNR, whereas this is not the case with FdII. The pH
      dependence of electron transfer by FdI, FdII, and an FdII mutant with FdI
      features was measured and further indicated that the binding mode to FNR differs
      between FdI and FdII. Based on this evidence, we hypothesize that binding modes
      with other Fd-dependent reductases may also vary between FdI and FdII. The
      structural differences between FdI and FdII therefore result in functional
      differences that may influence partitioning of electrons into different redox
      metabolic pathways.

PMID- 15513929
TI  - Functional segregation within pars opercularis of the inferior frontal gyrus:
      evidence from fMRI studies of imitation and action observation.
AB  - Recent neuroimaging studies have suggested that the inferior frontal gyrus (IFG)
      is important for action observation and imitation. In order to further explore
      the role of IFG in action observation and imitation, we pooled data from seven
      functional magnetic resonance imaging studies involving observation and imitation
      of simple finger movements performed in our laboratory. For imitation we found
      two peaks of activation in the pars opercularis, one in its dorsal sector and the
      other in its ventral sector. The dorsal sector of the pars opercularis was also
      activated during action observation, whereas the ventral sector was not. In
      addition, the pars triangularis was activated during action observation but not
      during imitation. This large dataset suggests a functional parcellation of the
      IFG that we discuss in terms of human mirror areas and the computational motor
      control architecture of internal models.

PMID- 15513930
TI  - Superoxide generation from Kupffer cells contributes to hepatocarcinogenesis:
      studies on NADPH oxidase knockout mice.
AB  - We hypothesized that superoxide from Kupffer cells (KC) contributes to
      hepatocarcinogenesis. p47phox(-/-) mice, deficient in phagocyte NADPH oxidase and
      superoxide generation, received a single dose of the hepatocarcinogen
      diethylnitrosamine (DEN). The following hepatic effects were observed at time
      points between 30 min and 35 days. Liver damage after DEN was manifested by loss
      of body and liver mass and of liver DNA and by an increase in apoptosis, necrosis
      and signs of inflammation. These effects were massive in wild-type (wt) male
      mice, but only very mild in p47phox(-/-) mice. Regenerative DNA synthesis
      subsequent to liver damage was high in wt male mice, but weak in p47phox(-/-)
      mice. In females the apparent protection by p47phox(-/-) was less pronounced than
      in males. Therefore, further experiments were performed with males. In KC
      isolated from wt mice superoxide production was enhanced by DEN pretreatment in
      vivo. Also, in vitro addition of DEN to KC cultures induced superoxide release,
      similarly to lipopolysaccharide, a standard KC activator. Thus, DEN directly
      activates wt KC to produce superoxide. KC from p47phox(-/-) mice did not release
      superoxide. TNFalpha production by isolated KC was transiently depressed 0.5 h
      after DEN treatment in vivo, but recovered rapidly. In blood serum TNFalpha
      levels of wt mice were elevated for the initial 6 h. TNFalpha in KC cultures and
      in serum of p47phox(-/-) mice was reduced. DEN in vivo induced DNA damage
      ('comets') in hepatocytes. This damage was extensive in wt mice but much less in
      p47phox(-/-) mice. These studies suggest two conclusions: (i) superoxide
      generation by phagocytes during liver damage and inflammation aggravates
      genotoxic and cytotoxic effects in hepatocytes and may thus contribute to tumor
      initiation and promotion; (ii) DEN has a direct stimulatory effect on KC to
      release superoxide and TNFalpha.

PMID- 15513931
TI  - Oct4 expression in adult human stem cells: evidence in support of the stem cell
      theory of carcinogenesis.
AB  - The Oct3/4 gene, a POU family transcription factor, has been noted as being
      specifically expressed in embryonic stem cells and in tumor cells but not in
      cells of differentiated tissues. With the ability to isolate adult human stem
      cells it became possible to test for the expression of Oct3/4 gene in adult stem
      cells and to test the stem cell theory of carcinogenesis. Using antibodies and
      PCR primers we tested human breast, liver, pancreas, kidney, mesenchyme and
      gastric stem cells, the cancer cell lines HeLa and MCF-7 and human, dog and rat
      tumors for Oct4 expression. The results indicate that adult human stem cells,
      immortalized non-tumorigenic cells and tumor cells and cell lines, but not
      differentiated cells, express Oct4. Oct4 is expressed in a few cells found in the
      basal layer of human skin epidermis. The data demonstrate that adult stem cells
      maintain expression of Oct4, consistent with the stem cell hypothesis of
      carcinogenesis.

PMID- 15513932
TI  - Selenomethionine induces sustained ERK phosphorylation leading to cell-cycle
      arrest in human colon cancer cells.
AB  - Selenomethionine (SeMet) is being tested alone and in combination with other
      agents in cancer chemoprevention trials. However, the molecular targets and the
      signaling mechanism underlying the anticancer effect of this compound are not
      completely clear. Here, we provide evidence that SeMet can induce cell-growth
      arrest and that the growth inhibition is associated with S-G2/M cell-cycle
      arrest. Coincidentally with the cell-cycle arrest, we observed a striking
      increase in cyclin B as well as phosphorylation of the cyclin-dependent kinase
      Cdc2. Since activation of the mitogen-activated protein kinase (MAPK) cascade has
      been associated with cell-cycle arrest and growth inhibition, we evaluated the
      activation of extracellular signal-regulated kinase (ERK). We found that SeMet
      induced phosphorylation of the MAPK ERK in a dose-dependent manner. We also
      demonstrate phosphorylation of ribosomal S6 kinase (p90RSK) by SeMet.
      Additionally, we show phosphorylation of histone H3 in a concentration-dependent
      manner. Furthermore, the phosphorylation of p90RSK and histone H3 were both
      antagonized by the MEK inhibitor U0126, implying that SeMet-induced
      phosphorylation of p90RSK and histone H3 are at least in part ERK pathway
      dependent. Based on these results, we propose that SeMet induced growth arrest
      and phosphorylation of histone H3 are mediated by persistent ERK and p90RSK
      activation. These new data provide valuable insights into the biological effects
      of SeMet at clinically relevant concentrations.

PMID- 15513933
TI  - Vasopressin-stimulated CFTR Cl- currents are increased in the renal collecting
      duct cells of a mouse model of Liddle's syndrome.
AB  - Liddle's syndrome is a genetic form of hypertension linked to Na(+) retention
      caused by activating mutations in the COOH terminus of the beta or gamma subunit
      of the epithelial sodium channel (ENaC). In this study, we used the short-circuit
      current (I(sc)) method to investigate the effects of deamino-8-d-arginine
      vasopressin (dDAVP) on Na(+) and Cl(-) fluxes in primary cultures of cortical
      collecting ducts (CCDs) microdissected from the kidneys of mice with Liddle's
      syndrome carrying a stop codon mutation, corresponding to the beta-ENaC R(566)
      stop mutation (L) found in the original pedigree. Compared to wild-type (+/+) CCD
      cells, untreated L/+ and L/L CCD cells exhibited 2.7- and 4.2-fold increases,
      respectively, in amiloride-sensitive (Ams) I(sc), reflecting ENaC-dependent Na(+)
      absorption. Short-term incubation with dDAVP caused a rapid and significant
      increase (approximately 2-fold) in Ams I(sc) in +/+, but not in L/+ or L/L CCD
      cells. In sharp contrast, dDAVP induced a greater increase in 5-nitro-2-(3
      phenylpropamino)benzoate (NPPB)-inhibited apical Cl(-) currents in amiloride
      treated L/L and L/+ cells than in their +/+ counterparts. I(sc) recordings
      performed under apical ion substituted conditions revealed that the dDAVP
      stimulated apical secretion of Cl(-), which was absent in cultured CCDs lacking
      CFTR, was 1.8-fold greater in L/+ and 3.7-fold greater in L/L CCD cells than in
      their +/+ CCD counterparts. After the basal membrane had been permeabilized with
      nystatin and a basal-to-apical Cl(-) gradient had been imposed, dDAVP also
      stimulated larger Cl(-) currents across L/L and L/+ CCD layers than +/+ CCD
      layers. These findings demonstrate that vasopressin stimulates greater apical
      CFTR Cl(-) conductance in the renal CCD cells of mice with Liddle's syndrome than
      in wild-type mice. This effect could contribute to the enhanced NaCl reabsorption
      observed in the distal nephron of patients with Liddle's syndrome.

PMID- 15513934
TI  - Kainate receptors and rhythmic activity in neuronal networks: hippocampal gamma
      oscillations as a tool.
AB  - Rhythmic electrical activity is ubiquitous in neuronal networks of the brain and
      is implicated in a multitude of different processes. A prominent example in the
      healthy brain is electrical oscillations in the gamma-frequency band (20-80 Hz)
      in hippocampal and neocortical networks, which play an important role in
      learning, memory and cognition. An example in the pathological brain is
      electrographic seizures observed in certain types of epilepsy. Interestingly the
      activation of kainate receptors (KARs) plays an important role in synaptic
      physiology and plasticity, and can generate both gamma oscillations and
      electrographic seizures. Electrophysiological recordings of extracellular gamma
      oscillations and intracellular currents in a hippocampal slice combined with
      computer modelling can shed light on the expression loci of KAR subunits on
      single neurones and the distinct roles subunits play in rhythmic activity in the
      healthy and the pathological brain. Using this approach in wild-type (WT) and KAR
      knockout mice it has been shown that KAR subunits GluR5 and GluR6 have similar
      functions during gamma oscillations and epileptiform bursts and that small
      changes in the overall activity in the hippocampal area CA3 can tilt the balance
      between excitation and inhibition and cause the neuronal network to switch from
      gamma oscillations to epileptiform bursts.

PMID- 15513935
TI  - Capacitative calcium entry supports calcium oscillations in human embryonic
      kidney cells.
AB  - Treatment of human epithelial kidney (HEK293) cells with low concentrations of
      the muscarinic agonist methacholine results in the activation of complex and
      repetitive cycling of intracellular calcium ([Ca(2+)](i)), known as [Ca(2+)](i)
      oscillations. These oscillations occur with a frequency that depends on the
      concentration of methacholine, whereas the magnitude of the [Ca(2+)](i) spikes
      does not. The oscillations do not persist in the absence of extracellular Ca(2+),
      leading to the conclusion that entry of Ca(2+) across the plasma membrane plays a
      significant role in either their initiation or maintenance. However, treatment of
      cells with high concentrations of GdCl(3), a condition which limits the flux of
      calcium ions across the plasma membrane in both directions, allows sustained
      [Ca(2+)](i) oscillations to occur. This suggests that the mechanisms that both
      initiate and regenerate [Ca(2+)](i) oscillations are intrinsic to the
      intracellular milieu and do not require entry of extracellular Ca(2+). This would
      additionally suggest that, under normal conditions, the role of calcium entry is
      to sustain [Ca(2+)](i) oscillations. By utilizing relatively specific
      pharmacological manoeuvres we provide evidence that the Ca(2+) entry that
      supports Ca(2+) oscillations occurs through the store-operated or capacitative
      calcium entry pathway. However, by artificial introduction of a non-store
      operated pathway into the cells (TRPC3 channels), we find that other Ca(2+) entry
      mechanisms can influence oscillation frequency in addition to the store-operated
      channels.

PMID- 15513936
TI  - NR2 subunit-dependence of NMDA receptor channel block by external Mg2+.
AB  - The vital roles played by NMDA receptors in CNS physiology depend critically on
      powerful voltage-dependent channel block by external Mg(2+) (Mg(2+)(o)). NMDA
      receptor channel block by Mg(2+)(o) depends on receptor subunit composition:
      NR1/2A receptors (receptors composed of NR1 and NR2A subunits) and NR1/2B
      receptors are more strongly inhibited by Mg(2+)(o) than are NR1/2C or NR1/2D
      receptors. We investigated the effects of Mg(2+)(o) on single-channel and whole
      cell currents recorded from recombinant NR1/2D and NR1/2A receptors expressed in
      HEK293 and 293T cells. The main conclusions are as follows: (1) Voltage-dependent
      inhibition by Mg(2+)(o) of whole-cell NR1/2D receptor responses was at least 4
      fold weaker than inhibition of NR1/2A receptor responses at all voltages tested.
      (2) Channel block by Mg(2+)(o) reduced the duration of NR1/2D receptor single
      channel openings; this reduction was used to estimate the apparent blocking rate
      of Mg(2+)(o) (k(+,app)). The k(+,app) for NR1/2D receptors was similar to but
      moderately slower than the k(+,app) obtained from cortical NMDA receptors
      composed of NR1, NR2A and NR2B subunits at all voltages tested. (3) Mg(2+)(o)
      blocking events induced an additional component in the closed-duration
      distribution; this component was used to estimate the apparent unblocking rate of
      Mg(2+)(o) (k(-,app)). The k(-,app) for NR1/2D receptors was much faster than the
      k(-,app) for cortical receptors at all voltages tested. The voltage-dependence of
      the k(-,app) of NR1/2D and cortical receptors differed in a manner that suggested
      that Mg(2+)(o) may permeate NR1/2D receptors more easily than cortical receptors.
      (4) Mg(2+)(o) inhibits NR1/2D receptors less effectively than cortical receptors
      chiefly because Mg(2+)(o) unbinds much more rapidly from NR1/2D receptors.

PMID- 15513937
TI  - Relations between substrate affinities and charge equilibration rates in the rat
      GABA cotransporter GAT1.
AB  - The relations between apparent affinity for substrates and operating rates have
      been investigated by two-electrode voltage clamp in the GABA transporter rGAT1
      expressed in Xenopus oocytes. We have measured the transport current induced by
      the presence of GABA, as well as the charge equilibration rate in the absence of
      the neurotransmitter, in various experimental conditions known to affect the
      transporter characteristics. The apparent affinities for GABA and for Na(+) were
      also determined in the same conditions. Two pharmacological actions and three
      mutated isoforms have been examined. In all cases significant correlations were
      found between the charge equilibration rates and apparent affinities for both
      substrates. In particular in the transport process, the apparent affinity for
      GABA appears to be inversely related to the sum of the unidirectional charge
      equilibration rates (alpha+beta), while the Na(+) apparent affinity is directly
      related to their ratio (beta/alpha). Together these observations suggest a
      kinetic basis for GABA affinity with higher turnover rates resulting in lower
      affinity, and indicate that an efficient uptake requires a compromise between
      these two parameters.

PMID- 15513938
TI  - Gender-modulated endogenous baseline neuropeptide Y Y1-receptor activation in the
      hindlimb of Sprague-Dawley rats.
AB  - This study examined the effect of neuropeptide Y Y(1)-receptor blockade both
      alone, and in interaction with alpha(1)-adrenoceptor antagonism, on basal
      hindlimb vascular conductance in male and female Sprague-Dawley rats. Hindlimb
      vascular conductance was measured during infusion of BIBP3226 (Y(1)-receptor
      antagonist; 100 microg kg(-1)), prazosin (alpha(1)-receptor antagonist; 20 microg
      kg(-1)), and combined blockade. In males, vascular conductance increased 1.1 +/-
      0.3 microl min(-1) mmHg(-1) above baseline with BIBP3226, and 2.4 +/- 0.4 microl
      min(-1) mmHg(-1) above baseline with prazosin (both P < 0.05). The increase in
      vascular conductance during combined blockade (5.1 +/- 0.7 microl min(-1) mmHg(
      1)) was greater than the sum of the independent BIBP3226 and prazosin responses
      (P < 0.05). In females, basal hindlimb vascular conductance was unaffected by
      Y(1)-receptor blockade. However, alpha(1)-receptor blockade resulted in a 3.5 +/-
      0.6 microl min(-1) mmHg(-1) increase in vascular conductance above baseline,
      which was not different than the combined blockade condition. Males had greater
      skeletal muscle neuropeptide Y concentration (P < 0.05; ELISA) than females.
      Furthermore, compared with females, male skeletal muscle contained greater Y(1)
      receptor expression (P < 0.05; Western blot). It was concluded that, under
      baseline conditions, agonist and receptor-based mechanisms for Y(1)-receptor
      dependent control of vascular conductance in skeletal muscle was greater in male
      versus female rats.

PMID- 15513939
TI  - The influence of normal human ageing on automatic movements.
AB  - There is evidence that aged normal subjects have more difficulty in achieving
      automaticity than young subjects. The underlying central neural mechanism for
      this phenomenon is unclear. In the present study, functional magnetic resonance
      imaging (fMRI) was used to investigate the effect of normal ageing on
      automaticity. Aged healthy subjects were asked to practice self-initiated, self
      paced, memorized sequential finger movements with different complexity until they
      could perform the tasks automatically. Automaticity was evaluated by having
      subjects perform a secondary task simultaneously with the sequential movements.
      Although it took more time, most aged subjects eventually performed the tasks
      automatically at the same level as the young subjects. Functional MRI results
      showed that, for both groups, sequential movements activated similar brain
      regions before and after automaticity was achieved. No additional activity was
      observed in the automatic condition. While performing automatic movements, aged
      subjects had greater activity in the bilateral anterior lobe of cerebellum,
      premotor area, parietal cortex, left prefrontal cortex, anterior cingulate,
      caudate nucleus and thalamus, and recruited more areas, including the pre
      supplementary motor area and the bilateral posterior lobe of cerebellum, compared
      to young subjects. These results indicate that most healthy aged subjects can
      perform some complex motor tasks automatically. However, aged subjects appear to
      require more brain activity to perform automatically at the same level as young
      subjects. This appears to be the main reason why aged subjects have more
      difficulty in achieving automaticity.

PMID- 15513940
TI  - Comparison of forearm blood flow responses to incremental handgrip and cycle
      ergometer exercise: relative contribution of nitric oxide.
AB  - The contribution of endothelium-derived nitric oxide (NO) to exercise hyperaemia
      remains controversial. Disparate findings may, in part, be explained by different
      shear stress stimuli as a result of different types of exercise. We have directly
      compared forearm blood flow (FBF) responses to incremental handgrip and cycle
      ergometer exercise in 14 subjects (age +/-s.e.m.) using a novel software system
      which calculates conduit artery blood flow continuously across the cardiac cycle
      by synchronising automated edge-detection and wall tracking of high resolution B
      mode arterial ultrasound images and Doppler waveform envelope analysis.
      Monomethyl arginine (L-NMMA) was infused during repeat bouts of each incremental
      exercise test to assess the contribution of NO to hyperaemic responses. During
      handgrip, mean FBF increased with workload (P < 0.01) whereas FBF decreased at
      lower cycle workloads (P < 0.05), before increasing at 120 W (P < 0.001).
      Differences in these patterns of mean FBF response to different exercise
      modalities were due to the influence of retrograde diastolic flow during cycling,
      which had a relatively larger impact on mean flows at lower workloads. Retrograde
      diastolic flow was negligible during handgrip. Although mean FBF was lower in
      response to cycling than handgrip exercise, the impact of L-NMMA was significant
      during the cycle modality only (P < 0.05), possibly reflecting the importance of
      an oscillatory antegrade/retrograde flow pattern on shear stress-mediated release
      of NO from the endothelium. In conclusion, different types of exercise present
      different haemodynamic stimuli to the endothelium, which may result in
      differential effects of shear stress on the vasculature.

PMID- 15513941
TI  - Metabotropic glutamate receptors modulate feedback inhibition in a
      developmentally regulated manner in rat dentate gyrus.
AB  - We investigated group II metabotropic glutamate receptor (mGluR) modulation of
      glutamatergic input onto hilar-border interneurones and its regulation of
      feedback inhibition in the dentate gyrus. Selective activation of group II mGluRs
      with (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV) depressed mossy
      fibre (MF)-evoked excitatory drive to these interneurones with significantly
      greater depression in juvenile than adult rats. During 20 Hz MF stimulus trains,
      EPSCs became depressed. Depression during the early, but not later part of the
      train was significantly greater in juvenile than adult rats and was blocked by
      the mGluR antagonist (2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9
      yl) propanoic acid (LY341495). In dentate granule cells from juvenile rats
      polysynaptic feedback IPSCs, but not monosynaptic IPSCs, were strongly suppressed
      by DCG-IV. DCG-IV also suppressed feedback inhibition of perforant path-evoked
      population spikes. In contrast, in adult animals DCG-IV did not significantly
      depress feedback inhibition. During 20 Hz stimulus trains in juvenile animals the
      summation of polysynaptic, but not monosynaptic IPSCs was suppressed by
      synaptically activated group II mGluRs. Blockade of these mGluRs with LY341495
      significantly increased the area and duration of the summated IPSC, causing
      greater feedback inhibition of granule cell firing. In contrast, in adult animals
      LY341495 did not alter feedback inhibition following the stimulus train. These
      findings indicate that group II mGluRs modulate excitatory drive to interneurones
      in a developmentally regulated manner and thereby modulate feedback inhibition in
      the dentate gyrus.

PMID- 15513942
TI  - Low threshold calcium currents in rat cerebellar Purkinje cell dendritic spines
      are mediated by T-type calcium channels.
AB  - The functional role of low voltage activated (LVA) calcium channels in the
      cerebellar Purkinje cell dendritic tree is not completely understood. Since the
      localization of these channels will influence their possible roles in dendritic
      integration and induction of plasticity, we set out to characterize the LVA
      calcium current in Purkinje cell dendrites in acute cerebellar slices of young
      rats. Using a combination of electrophysiological recordings and two-photon laser
      scanning microscopy, we show that LVA calcium current recorded at the soma can be
      correlated with voltage-dependent calcium transients in Purkinje cell dendritic
      spines. Blocking sodium and potassium conductances allowed us to isolate and
      characterize a fast inactivating inward current activated positive to -55 mV.
      Activation and steady-state inactivation kinetics, voltage-dependent deactivation
      kinetics, and pharmacological experiments (using omega-agatoxin-IVA, mibefradil
      and nickel) show that this current is carried by T-type calcium channels.
      Furthermore, the LVA calcium transient observed in the dendritic spines of the
      Purkinje cell is well correlated with the current recorded at the soma,
      suggesting that T-type calcium channels are the main component of the LVA calcium
      input in spines. The fast rising phase of the calcium transient in spines and the
      absence of delay between the onset in the spine and the parent dendrite show that
      T-type calcium channels are present both in spines and dendrites of the Purkinje
      cell.

PMID- 15513944
TI  - 5-Hydroxydecanoate is metabolised in mitochondria and creates a rate-limiting
      bottleneck for beta-oxidation of fatty acids.
AB  - 5-Hydroxydecanoate (5-HD) blocks pharmacological and ischaemic preconditioning,
      and has been postulated to be a specific inhibitor of mitochondrial ATP-sensitive
      K(+) (K(ATP)) channels. However, recent work has shown that 5-HD is activated to
      5-hydroxydecanoyl-CoA (5-HD-CoA), which is a substrate for the first step of beta
      oxidation. We have now analysed the complete beta-oxidation of 5-HD-CoA using
      specially synthesised (and purified) substrates and enzymes, as well as isolated
      rat liver and heart mitochondria, and compared it with the metabolism of the
      physiological substrate decanoyl-CoA. At the second step of beta-oxidation,
      catalysed by enoyl-CoA hydratase, enzyme kinetics were similar using either
      decenoyl-CoA or 5-hydroxydecenoyl-CoA as substrate. The last two steps were
      investigated using l-3-hydroxyacyl-CoA dehydrogenase (HAD) coupled to 3-ketoacyl
      CoA thiolase. V(max) for the metabolite of 5-HD (3,5-dihydroxydecanoyl-CoA) was
      fivefold slower than for the corresponding metabolite of decanoate (l-3
      hydroxydecanoyl-CoA). The slower kinetics were not due to accumulation of d-3
      hydroxyoctanoyl-CoA since this enantiomer did not inhibit HAD. Molecular
      modelling of HAD complexed with 3,5-dihydroxydecanoyl-CoA suggested that the 5
      hydroxyl group could decrease HAD turnover rate by interacting with critical side
      chains. Consistent with the kinetic data, 5-hydroxydecanoyl-CoA alone acted as a
      weak substrate in isolated mitochondria, whereas addition of 100 mum 5-HD-CoA
      inhibited the metabolism of decanoyl-CoA or lauryl-carnitine. In conclusion, 5-HD
      is activated, transported into mitochondria and metabolised via beta-oxidation,
      albeit with rate-limiting kinetics at the penultimate step. This creates a
      bottleneck for beta-oxidation of fatty acids. The complex metabolic effects of 5
      HD invalidate the use of 5-HD as a blocker of mitochondrial K(ATP) channels in
      studies of preconditioning.

PMID- 15513943
TI  - Effects of gestational age and cortisol treatment on ovine fetal heart function
      in a novel biventricular Langendorff preparation.
AB  - Structural and functional maturation of a number of fetal organs and
      physiological systems occurs in the immediate period prior to term, in
      association with the prepartum increase in fetal plasma cortisol concentration.
      At present, little is known about how myocardial sensitivity to adrenergic and
      muscarinic cholinergic stimulation changes as the fetus approaches term, nor the
      role of the prepartum increase in plasma cortisol concentration in mediating
      these changes. This study used a novel Langendorff, biventricular, ovine fetal
      heart preparation to investigate the effects of advancing gestation and cortisol
      treatment on myocardial sensitivity to adrenergic (isoprenaline) and muscarinic
      cholinergic (carbachol) stimulation. It was hypothesized that cortisol infusion
      would fully mimic developmental changes in myocardial responsiveness to
      adrenergic and cholinergic stimulation. Sixteen Welsh Mountain sheep fetuses were
      surgically prepared under general anaesthesia with vascular catheters. At 125 +/-
      1 days gestational age (dGA; term, 145 dGA) fetuses were infused with saline
      vehicle (n= 7; Premature Control) or with cortisol (n= 4; 2-3 mg kg(-1) d(
      1)i.v.; Premature Cortisol) for 5 days. The Term Control group (n= 5) comprised
      fetuses that were surgically prepared at 130 dGA and infused with vehicle for 5
      days prior to delivery (n= 2), or that received no surgery (n= 3). Under terminal
      anaesthesia, Premature Control and Premature Cortisol fetuses were delivered at
      130 dGA and Term Control fetuses between 135 and 143 dGA. Following
      exsanguination under anaesthesia, fetal hearts were mounted in the Langendorff
      preparation, allowing measurement of left ventricular (LV) developed pressure and
      right ventricular (RV) developed pressure, heart rate (HR), coronary perfusion
      pressure and perfusate distribution to the myocardium. Cortisol infusion elevated
      fetal plasma cortisol concentrations to values similar to those measured close to
      term (45.0 +/- 7.1 ng ml(-1)). Advancing gestational age, but not cortisol
      treatment, enhanced fetal LV developed pressure, RV developed pressure and HR
      responses to carbachol (P < 0.05). Advancing gestational age, but not cortisol
      treatment, suppressed fetal LV developed pressure, RV developed pressure and HR
      responses to isoprenaline (P < 0.05). Maximum doses of either carbachol or
      isoprenaline had no effect on coronary perfusate distribution. Changes in
      myocardial responsiveness to adrenergic and muscarinic cholinergic stimulation
      with advancing gestation provide mechanisms that contribute to the maturation of
      the cardiovascular system as the ovine fetus approaches term. These changes in
      myocardial responsiveness are not solely dependent on preparturient elevations in
      fetal plasma cortisol concentration.

PMID- 15513945
TI  - Raised dietary n-6 polyunsaturated fatty acid intake increases 2-series
      prostaglandin production during labour in the ewe.
AB  - Preterm labour is the major cause of perinatal morbidity and mortality in humans.
      The incidence is around 10% and the causes are often unknown. Consumption of
      dietary n-6 polyunsaturated fatty acids (PUFAs) in western societies is
      increasing. These are metabolized to arachidonic acid, the precursor for 2-series
      prostaglandins (PGs), major signalling molecules during labour. This study
      investigated the effect of dietary supplementation with linoleic acid (LA, 18: 2,
      n-6) on parturition. Ewes were fed a control or LA-supplemented diet from 100
      days gestation. Labour was induced using a standardized glucocorticoid challenge
      (dexamethasone, Dex) to the fetus, starting on day 139. Electromyographic (EMG)
      activity and fetal and maternal circulating PG concentrations were monitored. One
      third of LA-fed ewes delivered early (pre-Dex) although basal uterine EMG
      activity preceding Dex was higher in control ewes (P < 0.05). A steep increase in
      EMG activity occurred 18-38 h after the start of Dex infusion. Twice basal EMG
      activity (defined as established labour) occurred on average 7 h earlier in the
      LA-supplemented ewes (P < 0.05). The basal concentrations of maternal and fetal
      PGFM and fetal PGE(2) were approximately doubled in LA-supplemented ewes before
      the start of Dex infusion (P < 0.01). The rise in fetal PGE(2) and maternal
      oestradiol concentrations post-Dex occurred earlier in the LA-supplemented ewes.
      All PG measurements remained significantly higher in the LA-supplemented ewes
      during labour onset. This study suggests that consumption of a high LA diet in
      late pregnancy can enhance placental PG production and may thus increase the risk
      of preterm labour.

PMID- 15513946
TI  - Pancreatic two P domain K+ channels TALK-1 and TALK-2 are activated by nitric
      oxide and reactive oxygen species.
AB  - This study firstly shows with in situ hybridization on human pancreas that TALK-1
      and TALK-2, two members of the 2P domain potassium channel (K(2P)) family, are
      highly and specifically expressed in the exocrine pancreas and absent in
      Langherans islets. On the contrary, expression of TASK-2 in mouse pancreas is
      found both in the exocrine pancreas and in the Langherans islets. This study also
      shows that TALK-1 and TALK-2 channels, expressed in Xenopus oocytes, are strongly
      and specifically activated by nitric oxide (obtained with a mixture of sodium
      nitroprussate (SNP) and dithiothreitol (DTT)), superoxide anion (obtained with
      xanthine and xanthine oxidase) and singlet oxygen (obtained upon photoactivation
      of rose bengal, and with chloramine T). Other nitric oxide and reactive oxygen
      species (NOS and ROS) donors, as well as reducing conditions were found to be
      ineffective on TALK-1, TALK-2 and TASK-2 (sin-1, angeli's salt, SNP alone, tBHP,
      H(2)O(2), and DTT). These results suggest that, in the exocrine pancreas,
      specific members of the NOS and ROS families could act as endogenous modulators
      of TALK channels with a role in normal secretion as well as in disease states
      such as acute pancreatitis and apoptosis.

PMID- 15513947
TI  - Increased corticospinal excitability after 5 Hz rTMS over the human supplementary
      motor area.
AB  - Transcranial magnetic stimulation (TMS) can produce effects not only at the site
      of stimulation but also at distant sites to which it projects. Here we examined
      the connection between supplementary motor area (SMA) and the hand area of the
      primary motor cortex (M1(Hand)) by testing whether prolonged repetitive TMS
      (rTMS) over the SMA can produce changes in excitability of the M1(Hand) after the
      end of the stimulus train. We evaluated motor-evoked potentials (MEPs) and the
      cortical silent period (CSP) evoked by a single-pulse TMS, short-interval
      intracortical inhibition (SICI) and intracortical facilitation (ICF) produced by
      a paired-pulse TMS, and forearm flexor H reflexes before and after 750 pulses of
      5 Hz rTMS over SMA at an intensity of 110% active motor threshold (AMT) for the
      first dorsal interosseous (FDI) muscle. The amplitude of MEPs recorded from the
      right FDI muscle at rest as well as during voluntary contraction increased for at
      least 10 min after the end of rTMS, although the duration of the CSP, SICI and
      ICF did not change. There was no effect on H reflexes in the flexor carpi
      radialis muscle, even though the amplitude of the MEP obtained from the same
      muscle increased after rTMS. The effects on MEPs depended on the intensity of
      rTMS and were spatially specific to the SMA proper. We suggest that 5 Hz rTMS
      over SMA can induce a short-lasting facilitation in excitability of the M1(Hand)
      compatible with the anatomical connections between SMA and the M1(Hand).

PMID- 15513949
TI  - Prenatal nicotine exposure increases the strength of GABA(A) receptor-mediated
      inhibition of respiratory rhythm in neonatal rats.
AB  - Infants born to mothers that smoke while pregnant have a relatively high
      incidence of central respiratory control abnormalities. Recent studies have shown
      that prenatal nicotine exposure increases GABA release and the frequency of
      GABAergic currents, leading to an up-regulation of GABA(A) receptors in central
      neurones. Activation of GABA(A) receptors inhibits ventilatory activity, with
      intense activation causing apnoea. These observations lead us to hypothesize that
      prenatal nicotine exposure alters GABAergic control of respiratory motor pattern
      in the early neonatal period. Osmotic minipumps were implanted in pregnant
      Sprague-Dawley rats on the fifth day of gestation, and filled with nicotine (6 mg
      kg(-1) day(-1), 2.5 microl h(-1)) or physiological saline (2.5 microl h(-1)).
      Brainstem-spinal cord preparations from 1- to 3-day-old neonates were studied
      under in vitro conditions. Electrical activity was recorded from the fourth
      cervical ventral root (C4 VR), which contains the axons of phrenic motoneurones.
      Bath application of GABA(A) receptor agonists muscimol (250 microM) or
      pentobarbital sodium (60 microM) to the brainstem led to consistent, reversible
      and significant reductions in C4 VR burst frequency. In saline-exposed animals,
      frequency (bursts min(-1)) fell from 6.8 +/- 0.4 to a nadir of 2.8 +/- 0.5 with
      muscimol, and from 6.5 +/- 0.3 to a nadir of 2.9 +/- 0.3 for pentobarbital; in
      nicotine-exposed animals, frequency fell from 6.3 +/- 0.4 to 1.0 +/- 0.4 with
      muscimol and from 6.4 +/- 0.2 to 1.7 +/- 0.4 with pentobarbital (P < 0.05 in all
      cases). The decrease in C4 VR frequency was significantly greater in nicotine
      exposed compared to saline-exposed preparations with both muscimol and
      pentobarbital (P < 0.001 for both). There were no changes in the amplitude of C4
      VR bursts under any condition. The GABA(A) receptor antagonist bicuculline
      methiodide (8 microM) did not change C4 VR frequency or amplitude in either
      group, although it was effective in reversing the effects of muscimol. These
      experiments demonstrate that prenatal nicotine exposure alters the GABAergic
      regulation of respiratory rhythm in a reduced preparation. The results may lead
      to a better understanding of the perturbed breathing pattern observed in neonates
      that are exposed to nicotine in utero.

PMID- 15513948
TI  - Differential effects of insulin and dietary amino acids on muscle protein
      synthesis in adult and old rats.
AB  - The potential roles of insulin and dietary amino acids in the regulation of
      skeletal muscle protein synthesis were examined in adult and old rats. Animals
      were fed over 1 h with either a 25% or a 0% amino acid/protein meal. In each
      nutritional condition, postprandial insulin secretion was either maintained or
      blocked with diazoxide injections. Protein synthesis in gastrocnemius and soleus
      muscles was assessed in vivo using the flooding dose method. Insulin suppression
      decreased protein synthesis in both muscles irrespective of the nutritional
      condition and age of the rats. Moreover, reduced insulinaemia was associated with
      4E-BP1 dephosphorylation, enhanced assembly of the 4E-BP1-eIF4E inactive complex
      and hypophosphorylation of eIF4E, p70S6k and protein kinase B, key intermediates
      in the regulation of translation initiation and protein synthesis. Old rats did
      not differ from adult rats. The lack of amino acids in the meal of insulin
      suppressed rats did not result in any additional decrease in protein synthesis.
      In the presence of insulin secretion, dietary amino acid suppression
      significantly decreased gastrocnemius protein synthesis in adult but not in old
      rats. Amino acid suppression was associated with reduced phosphorylation of 4E
      BP1 and p70S6k in adults. Along with protein synthesis, only the inhibition of
      p70S6k phosphorylation was abolished in old rats. We concluded that insulin is
      required for the regulation of muscle protein synthesis irrespective of age and
      that the effect of dietary amino acids is blunted in old rats.

PMID- 15513950
TI  - Effects of chronic portal hypertension on small heat-shock proteins in mesenteric
      arteries.
AB  - Previous studies have shown that impaired vasoconstrictor function in chronic
      portal hypertension is mediated via cAMP-dependent events. Recent data have
      implicated two small heat-shock proteins (HSP), namely HSP20 and HSP27, in the
      regulation of vascular tone. Phosphorylation of HSP20 is associated with
      vasorelaxation, whereas phosphorylation of HSP27 is associated with
      vasoconstriction. We hypothesized that alterations in the expression and/or
      phosphorylation of small HSPs may play a role in impaired vasoconstriction in
      portal hypertension. A rat model of prehepatic chronic portal hypertension was
      used. Studies were conducted in small mesenteric arteries isolated from normal
      and portal hypertensive rats. Protein levels of HSP20 and HSP27 were detected by
      Western blot analysis. Protein phosphorylation was analyzed by isoelectric
      focusing. HSP20 mRNA expression was determined by RT-PCR. To examine the role of
      cAMP in the regulation of small HSP phosphorylation and expression, we treated
      both normal and portal hypertensive vessels with a PKA inhibitor Rp-cAMPS. We
      found both an increased HSP20 phosphorylation and a decreased HPS20 protein level
      in portal hypertension, both of which were restored to normal by PKA inhibition.
      However, PKA did not change HSP20 mRNA expression. We conclude that decreased
      HSP20 protein level is mediated by cAMP-dependent pathway and that impaired
      vasoconstrictor function in portal hypertension may be partially explained by
      decreased expression of HSP20. We also suggest that the phosphorylation of HSP20
      by PKA may alter HSP20 turnover.

PMID- 15513951
TI  - Heat-stable enterotoxin of Escherichia coli stimulates a non-CFTR-mediated
      duodenal bicarbonate secretory pathway.
AB  - The cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is an
      important pathway for duodenal mucosal bicarbonate secretion. Duodenal biopsies
      from CF patients secrete bicarbonate in response to heat-stable enterotoxin from
      Escherichia coli (STa) but not cAMP. To explore the mechanism of STa-induced
      bicarbonate secretion in CF more fully, we examined the role of CFTR in STa
      stimulated duodenal bicarbonate secretion in mice. In vivo, the duodenum of CFTR
      (-/-) or control mice was perfused with forskolin (10(-4) M), STa (10(-7) M),
      uroguanylin (10(-7) M), 8-bromoguanosine 3',5'-cGMP (8-Br-cGMP) (10(-3) M),
      genistein (10(-6) M) plus STa, or herbimycin A (10(-6) M) plus STa. In vitro,
      duodenal mucosae were voltage-clamped in Ussing chambers, and bicarbonate
      secretion was measured by pH-stat. The effect of genistein, DIDS (10(-4) M), and
      chloride removal was also studied in vitro. Control, but not CF, mice produced a
      significant increase in duodenal bicarbonate secretion after perfusion with
      forskolin, uroguanylin, or 8-Br-cGMP. However, both control and CF animals
      responded to STa with significant increases in bicarbonate output. Genistein and
      herbimycin A abolished this response in CF mice but not in controls. In vitro,
      STa-stimulated bicarbonate secretion in CF tissues was inhibited by genistein,
      DIDS, and chloride-free conditions, whereas bicarbonate secretion persisted in
      control mice. In the CF duodenum, STa can stimulate bicarbonate secretion via
      tyrosine kinase activity resulting in apical Cl(-)/HCO(3)(-) exchange. Further
      studies elucidating the intracellular mechanisms responsible for such non-CFTR
      mediated bicarbonate secretion may lead to important therapies for CF.

PMID- 15513953
TI  - Dietary lipids modify the age-associated changes in intestinal uptake of fructose
      in rats.
AB  - Because reduced nutrient absorption may contribute to malnourishment in the
      elderly, age and diet modulate fructose uptake in mice, and alterations in
      fructose uptake may be paralleled by changes in the abundance of fructose
      transporters, the objectives of this study were to determine 1) the effects of
      aging on fructose absorption in rats, 2) the effect of feeding diets enriched
      with saturated fatty acids (SFA) vs. polyunsaturated fatty acids (PUFA), and 3)
      the mechanisms of these age-and diet-associated changes. Male Fischer 344 rats
      aged 1, 9, and 24 mo received isocaloric diets enriched with SFA or PUFA. The
      uptake of (14)C-labeled D-fructose was determined in vitro using the intestinal
      sheet method. Northern and Western blot analyses and immunohistochemistry were
      used to determine the abundance of sodium-independent glucose and fructose
      transporters (GLUT)2 and GLUT5. When expressed on the basis of mucosal surface
      area, jejunal fructose uptake was increased in 9 and 24 mo compared with 1-mo-old
      animals fed SFA. PUFA-fed animals demonstrated increased fructose uptake at 24 mo
      compared with younger animals. Ileal fructose uptake was increased with SFA vs.
      PUFA in 9-mo-old rats but was reduced with SFA in 1- and 24-mo-old rats.
      Variations in GLUT2 and GLUT5 abundance did not parallel changes in uptake. These
      results indicate that 1) age increases fructose uptake when expressed on the
      basis of mucosal surface area, 2) age influences the adaptive response to dietary
      lipid modifications, and 3) alterations in fructose uptake are not explained by
      variations in GLUT2 or GLUT5.

PMID- 15513952
TI  - Epinephrine induces tissue perfusion deficit in porcine endotoxin shock:
      evaluation by regional CO(2) content gradients and lactate-to-pyruvate ratios.
AB  - Epinephrine is widely used as a vasoconstrictor or inotrope in shock, although it
      may typically induce or augment lactic acidosis. Ongoing debate addresses the
      question of whether hyperlactatemia per se is a sign of tissue perfusion deficit
      or aerobic glycolysis. We wanted to test the hypothesis that epinephrine has
      selective detrimental effects on visceral perfusion and metabolism. We performed
      rigorous regional venous blood gas analyses as well as intraperitoneal
      microdialysis. We used a mathematical model to calculate regional arteriovenous
      CO(2) content gradients and estimated the magnitude of the Haldane effect in a
      porcine model of prolonged hypotensive shock induced by endotoxin infusion (mean
      arterial blood pressure < 60 mmHg). Subsequently, vasopressors (epinephrine or
      norepinephrine) were administered and adjusted to maintain systemic mean arterial
      pressure > 70 mmHg for 4 h. Epinephrine caused systemic hyperlactatemia and
      acidosis. Importantly, both systemic and regional venous lactate-to-pyruvate
      ratios increased. Epinephrine was associated with decreasing portal blood flow
      despite apparently maintained total splanchnic blood flow. Epinephrine increased
      gastric venous-to-arterial Pco(2) gradients and CO(2) content gradients with
      decreasing magnitude of the Haldane effect, and the regional gastric respiratory
      quotient remained higher after epinephrine as opposed to norepinephrine infusion.
      In addition, epinephrine induced intraperitoneal lactate and glycerol release. We
      did not observe these adverse hemodynamic or metabolic changes related to
      norepinephrine with the same arterial pressure goal. We conclude that high CO(2)
      content gradients with decreasing magnitude of the Haldane effect pinpoint the
      most pronounced perfusion deficiency to the gastric wall when epinephrine, as
      opposed to norepinephrine, is used in experimental endotoxin shock.

PMID- 15513954
TI  - Effects of yo-yo diet, caloric restriction, and olestra on tissue distribution of
      hexachlorobenzene.
AB  - Chlorinated hydrocarbons are lipophilic, toxic, and persistent in the environment
      and animal tissues. They enter the body in food and are stored in adipose tissue.
      Loss of body fat through caloric restriction mobilizes stored lipophilic
      xenobiotics and results in distribution to other tissues. We have studied the
      reversibility of this process in mice that followed a regimen of body weight
      cycling. Weight gain was followed by weight loss, a second gain, and a second
      loss ("yo-yo diet regimen"). We measured the distribution of orally gavaged
      [14C]hexachlorobenzene, which is sparingly metabolized. We found that weight
      cycling has different effects in different organs. Continued weight loss resulted
      in a threefold increase of 14C amount and concentration in the brain. After
      weight regain, 14C in the brain decreased but then increased again after a second
      weight loss. Weight loss resulted in an increase in the concentration of 14C in
      adipose tissue without changing the total amount in that tissue. Weight loss and
      regain resulted in an increase of 14C in the liver, which reflected an increase
      of fat in the liver. The regimen of weight gain and loss was repeated in mice
      gavaged with [14C]hexachlorobenzene, with one group receiving the nonabsorbable
      fat olestra in the diet. Combined dietary olestra and caloric restriction caused
      a 30-fold increase in the rate of excretion of 14C relative to an ad libitum diet
      or a reduced caloric diet alone. Distribution of 14C into the brain resulting
      from the restricted diet was reduced by 50% by dietary olestra.

PMID- 15513955
TI  - Impaired agonist-dependent myosin phosphorylation and decreased RhoA in rat
      portal hypertensive mesenteric vasculature.
AB  - The purpose of the present study was to examine the effects of portal
      hypertension on agonist-induced myosin phosphorylation and RhoA expression in
      vascular smooth muscle. A possible link to cAMP-dependent events was also
      examined. Portal hypertension was produced by stenosis of the portal vein. Vessel
      segments were treated with or without 50 microM of the PKA inhibitor Rp-cAMPS for
      30 min and subsequently stimulated with 10(-4) M phenylephrine. Myosin regulatory
      light-chain phosphorylation was detected by immunoblotting. Total RNA from first
      order mesenteric arteries and portal veins was isolated and amplified by RT-PCR
      using RhoA and GAPDH primers. RhoA protein expression was also measured in first
      order mesenteric arteries using Western blot analysis. Myosin phosphorylation in
      maximally stimulated first-order mesenteric arteries was significantly lower in
      portal hypertensive animals (19.9 +/- 2.86%) when compared with sham-operated
      control (43.8 +/- 3.53%). Inhibition of PKA selectively increased myosin
      phosphorylation to 34.7 +/- 4.18%. Rp-cAMPS did not affect the phosphorylation of
      the portal veins or superior mesenteric arteries. RhoA mRNA and membrane
      associated RhoA protein expression in portal hypertensive first-order mesenteric
      arteries were significantly lower when compared with controls. Acute inhibition
      of PKA had no effect on RhoA mRNA expression. However, it restored membrane
      associated RhoA protein expression in portal hypertensive vessels to control
      levels. The results suggest that reductions in membrane-associated RhoA
      expression, which appear to be regulated by cAMP-dependent events, lead to
      reduced myosin phosphorylation and may underlie the reduced vasoconstrictor
      effectiveness in the resistance vasculature of portal hypertensive intestine.

PMID- 15513956
TI  - Primary care and health system performance: adults' experiences in five
      countries.
AB  - This paper reports on a 2004 survey of primary care experiences among adults in
      Australia, Canada, New Zealand, the United Kingdom, and the United States. The
      survey finds shortfalls in delivery of safe, effective, timely, or patient
      centered care, with variations among countries. Delays in lab test results and
      test errors raise safety concerns. Failures to communicate, to engage patients,
      or to promote health are widespread. Aside from clinical preventive care, the
      United States performs poorly on most care dimensions in the study, with notable
      cost-related access concerns and short-term physician relationships. Contrasts
      across countries point to the potential to improve performance and to learn from
      international initiatives.

PMID- 15513957
TI  - The role of PBMs in implementing the Medicare prescription drug benefit.
AB  - In creating the Medicare prescription drug benefit and stipulating that it be
      managed by private-sector prescription drug insurance plans, Congress opened a
      huge business opportunity for pharmacy benefit managers (PBMs). Although hardly
      noticed by the general public, PBMs already administer prescription drug benefits
      for nearly everyone with employer coverage and for many Medicaid recipients. The
      new law contains requirements for Medicare drug plan sponsors that could
      challenge some PBMs--most notably, the requirement to assume insurance risk. This
      paper explores challenges to PBMs' business practices and provisions of the
      Medicare benefit that will require them to adapt their mode of operation.

PMID- 15513958
TI  - Nitric oxide contributes to right coronary vasodilation during systemic hypoxia.
AB  - As arterial partial pressure of O(2) (Pa(O(2))) is reduced during systemic
      hypoxia, right ventricular (RV) work and myocardial O(2) consumption (MVo(2))
      increase. Mechanisms responsible for maintaining RV O(2) demand/supply balance
      during hypoxia have not been delineated. To address this problem, right coronary
      (RC) blood flow and RV O(2) extraction were measured in nine conscious,
      instrumented dogs exposed to normobaric hypoxia. Catheters were implanted in the
      right ventricle for measuring pressure, in the ascending aorta for measuring
      arterial pressure and for sampling arterial blood, and in an RC vein. A flow
      transducer was placed around the RC artery. After recovery from surgery, dogs
      were exposed to hypoxia in a chamber ventilated with N(2), and blood samples and
      hemodynamic data were collected as chamber O(2) was reduced progressively to
      approximately 8%. After control measurements were made, the chamber was opened
      and the dog was allowed to recover. N(omega)-nitro-L-arginine (L-NNA) was then
      administered (35 mg/kg, via RV catheter) to inhibit nitric oxide (NO) production,
      and the hypoxia protocol was repeated. RC blood flow increased during hypoxia due
      to coronary vasodilation, because RC conductance increased from 0.65 +/- 0.05 to
      1.32 +/- 0.12 ml x min(-1) x 100 g(-1) x L-NNA blunted the hypoxia-induced
      increase in RC conductance. RV O(2) extraction remained constant at 64 +/- 4% as
      Pa(O(2)) was decreased, but after L-NNA, extraction increased to 70 +/- 3% during
      normoxia and then to 78 +/- 3% during hypoxia. RV MVo(2) increased during
      hypoxia, but after L-NNA, MVo(2) was lower at any respective Pa(O(2)). The
      relationship between heart rate times RV systolic pressure (rate-pressure
      product) and RV MVo(2) was not altered by l-NNA. To account for L-NNA-mediated
      decreases in RV MVo(2), O(2) demand/supply variables were plotted as functions of
      MVo(2). Slope of the conductance-MVo(2) relationship was depressed by L-NNA (P =
      0.03), whereas the slope of the extraction-MVo(2) relationship increased (P =
      0.003). In summary, increases in RV MVo(2) during hypoxia are met normally by
      increasing RC blood flow. When NO synthesis is blocked, the large RV O(2)
      extraction reserve is mobilized to maintain RV O(2) demand/supply balance. We
      conclude that NO contributes to RC vasodilation during systemic hypoxia.

PMID- 15513959
TI  - Experimental analysis of critical oxygen delivery.
AB  - Systemic variables were evaluated with respect to O(2) delivery to test the
      hypothesis that critical O(2) delivery and critical Hb can be estimated by
      multiple variables collected simultaneously. Rats were subjected to transfusion
      with either fresh or stored blood and then subjected to stepwise isovolemic
      hemodilution. Critical levels were measured by the dual-regression method from
      plots of systemic variables against O(2) delivery and Hb. Delivery was calculated
      from cardiac index and arterial O(2) content. We found that 1) after
      hemodilution, O(2) delivery changed in a nonlinear relationship with Hb; 2)
      critical delivery calculated using 30 different systemic variables was not
      statistically different from each other; 3) critical delivery and critical Hb
      were correlated but were not different between animals receiving fresh or stored
      blood; and 4) similar critical levels were found using a single variable from
      several animals and using several variables from the same subject. The best
      variables to estimate critical delivery were lactate, bicarbonate, base excess,
      O(2) extraction ratio, expired CO(2), pulse pressure, cardiac index, and systolic
      pressure. The data suggest that a multivariable analysis of critical delivery may
      help determine the physiological oxygenation boundary at the whole body level.
      This may assist in finding therapeutic triggers on an individual basis using
      systemic markers of the transition from aerobic to anaerobic metabolism.

PMID- 15513961
TI  - Regulatory response to washout of amniotic fluid in sheep.
AB  - To test the hypothesis that a substance present in the amniotic fluid could serve
      as a regulator of amniotic fluid volume, we drained and discarded amniotic fluid
      while replacing it with lactated Ringer solution that was isotonic to amniotic
      fluid. Seven ewes with singleton fetuses at 119 +/- 1 days of gestation (mean +/-
      SE) were instrumented with multiple indwelling catheters in the pedal artery,
      pedal vein, and amniotic cavity. During the exchange periods, an average of 3,019
      +/- 171 ml/day of lactated Ringer solution was infused into the amniotic cavity
      while an equal amount of amniotic fluid was pumped out and discarded. During the
      control period, amniotic fluid composition and volume were not altered. Exchange
      and control periods started with the same amniotic fluid volume, lasted 3 or 4
      days, and were randomized with regard to order. Amniotic fluid volume measured by
      vacuum drainage was 556 +/- 98 ml at the end of the control period and 986 +/-
      209 ml (P = 0.03) at the end of the exchange period. Fetal arterial blood gases,
      hemodynamic parameters and the osmolality gradient between fetal plasma and
      amniotic fluid were not altered by the exchange process. A linear relationship
      between the control amniotic fluid volume and the volume at the end of the
      exchange period (P = 0.003) suggests that the animals with larger control volumes
      responded to isovolumic dilution with a larger volume increase. We conclude that
      amniotic fluid may contain a substance that regulates amniotic volume.

PMID- 15513960
TI  - Dynamic model for ventricular junctional conductance during the cardiac action
      potential.
AB  - The ventricular action potential was applied to paired neonatal murine
      ventricular myocytes in the dual whole cell configuration. During peak action
      potential voltages >100 mV, junctional conductance (g(j)) declined by 50%. This
      transjunctional voltage (V(j))-dependent inactivation exhibited two time
      constants that became progressively faster with increasing V(j). G(j) returned to
      initial peak values during action potential repolarization and even exceeded peak
      g(j) values during the final 5% of repolarization. This facilitation of g(j) was
      observed <30 mV during linearly decreasing V(j) ramps. The same behavior was
      observed in ensemble averages of individual gap junction channels with unitary
      conductances of 100 pS or lower. Immunohistochemical fluorescent micrographs and
      immunoblots detect prominent amounts of connexin (Cx)43 and lesser amounts of
      Cx40 and Cx45 proteins in cultured ventricular myocytes. The time dependence of
      the g(j) curves and channel conductances are consistent with the properties of
      predominantly homomeric Cx43 gap junction channels. A mathematical model
      depicting two inactivation and two recovery phases accurately predicts the
      ventricular g(j) curves at different rates of stimulation and repolarization.
      Functional differences are apparent between ventricular myocytes and Cx43
      transfected N2a cell gap junctions that may result from posttranslational
      modification. These observations suggest that gap junctions may play a role in
      the development of conduction block and the genesis and propagation of triggered
      arrhythmias under conditions of slowed conduction (<10 cm/s).

PMID- 15513962
TI  - Evolution of a "falx lunatica" in demarcation of critically ischemic myocutaneous
      tissue.
AB  - Using intravital microscopy in a chronic in vivo mouse model, we studied the
      demarcation of myocutaneous flaps and evaluated microvascular determinants for
      tissue survival and necrosis. Chronic ischemia resulted in a transition zone,
      characterized by a red fringe and a distally adjacent white falx, which defined
      the demarcation by dividing the proximally normal from the distally necrotic
      tissue. Tissue survival in the red zone was determined by hyperemia, as indicated
      by recovery of the transiently reduced functional capillary density, and
      capillary remodeling, including dilation, hyperperfusion, and increased
      tortuosity. Angiogenesis and neovascularization were not observed over the 10-day
      observation period. The white rim distal to the red zone, appearing as "falx
      lunatica," showed a progressive decrease of functional capillary density similar
      to that of the necrotic distal area but without desiccation, and thus
      transparency, of the tissue. Development of the distinct zones of the critically
      ischemic tissue could be predicted by partial tissue oxygen tension (Pt(O(2)))
      analysis by the time of flap elevation. The falx lunatica evolved at a Pt(O(2))
      between 6.2 +/- 1.3 and 3.8 +/- 0.7 mmHg, whereas tissue necrosis developed at
      <3.8 +/- 0.7 mmHg. Histological analysis within the falx lunatica revealed
      interstitial edema formation and muscle fiber nuclear rarefaction but an absence
      of necrosis. We have thus demonstrated that ischemia-induced necrosis does not
      demarcate sharply from normal tissue but develops beside a fringe of tissue with
      capillary remodeling an adjacent falx lunatica that survives despite nutritive
      capillary perfusion failure, probably by direct oxygen diffusion.

PMID- 15513963
TI  - Measurement of myocardial mechanics in mice before and after infarction using
      multislice displacement-encoded MRI with 3D motion encoding.
AB  - Cardiac MRI is an accurate, noninvasive modality for assessing the structure and
      function of the murine heart. In addition to conventional imaging, MRI tissue
      tracking methods can quantify numerous aspects of myocardial mechanics, including
      intramyocardial displacement, strain, twist, and torsion. In the present study,
      we developed and applied a novel pulse sequence based on displacement-encoded
      imaging using stimulated echoes (DENSE) that achieves multislice coverage, high
      spatial resolution, and three-dimensional (3D) displacement encoding. With the
      use of this technique, myocardial mechanics of C57Bl/6 mice were measured at
      baseline and 1 day after experimental myocardial infarction. At baseline, the
      mean systolic transmural circumferential strain was -0.14 +/- 0.02 and the mean
      systolic radial strain was 0.30 +/- 0.05. Changes in circumferential and radial
      strains from the subepicardium to the subendocardium were detected at baseline (P
      < 0.05). One day after infarction, significantly reduced 3D displacements and
      strain were detected in infarcted and noninfarcted myocardium. Infarction also
      reduced normalized systolic torsion from its baseline value of 1.35 +/- 0.27
      degrees /mm (R = 0.99) to 0.07 +/- 0.54 degrees /mm (R = 0.96, P < 0.05). DENSE
      MRI can assess the 3D myocardial mechanics of the murine heart in <1 h of scan
      time at 4.7 T and may be applied to studies of myocardial mechanics in
      genetically engineered mice.

PMID- 15513964
TI  - Meal-related increases in vascular reactivity are impaired in older and diabetic
      adults: insights into roles of aging and insulin in vascular flow.
AB  - A fatty meal induces vasodilatation (of both resting and stimulated forearm flow)
      in healthy young adults, an effect most likely mediated by the vasodilator
      actions of insulin. We therefore hypothesized that an impaired meal-related
      vascular response might be an in vivo marker of vascular insulin resistance,
      related to the presence of diabetes and/or higher age. Postprandial vascular
      responses were assessed in three groups of subjects: 15 Type 2 diabetic subjects
      (age 58 +/- 8 yr), 15 age-, gender-, and body mass index (BMI)-matched older
      control subjects (age 57 +/- 9 yr), and 15 healthy young control subjects (age 33
      +/- 7 yr). Studies were carried out before and 3 and 6 h after a standardized
      high-fat meal (1,030 kcal, 61 g fat). Forearm microvascular flows were measured
      by strain gauge plethysmography and large-artery function by ultrasound. Resting
      blood flow and hyperemic area under curve (AUC) flow were not significantly
      different in diabetic subjects (resting 117 +/- 42% and AUC 134 +/- 46% of
      premeal values) compared with age-matched controls (resting 131 +/- 39% and AUC
      134 +/- 47%); however, the response in diabetic subjects was blunted compared
      with young controls (resting 171 +/- 67% and AUC 173 +/- 99% of premeal values; P
      = 0.02 and P = 0.18, respectively). On multiple regression analysis, we found
      that increasing age (but not BMI or diabetes) was significantly associated with
      impaired postprandial vascular responses (resting: r = -0.4, P = 0.002; AUC: r = 
      0.4, P = 0.006). Therefore, meal ingestion results in impaired vasodilator
      responses in older nondiabetic and diabetic adults, related to aging rather than
      insulin resistance.

PMID- 15513965
TI  - cTnT1, a cardiac troponin T isoform, decreases myofilament tension and affects
      the left ventricular pressure waveform.
AB  - Four isoforms of cardiac troponin T (cTnT), a protein essential for calcium
      dependent myocardial force development, are expressed in the human; they differ
      in charge and length. Their expression is regulated developmentally and is
      affected by disease states. Human cTnT (hcTnT) isoform effects have been examined
      in reconstituted myofilaments. In this study, we evaluated the modulatory effects
      of overexpressing one cTnT isoform on in vitro and in vivo myocardial function. A
      hcTnT isoform, hcTnT(1), expressed during development and in heart disease but
      not in the normal adult heart, was expressed in transgenic (TG) mice (1-30% of
      total cTnT). Maximal active tension measured in skinned myocardium decreased as a
      function of relative hcTnT(1) expression. The pCa at half-maximal force
      development, Hill coefficient, and rate of redevelopment of force did not change
      significantly with hcTnT(1) expression. In vivo maximum rates of rise and fall of
      left ventricular pressure decreased, and the half-time of isovolumic relaxation
      increased, with hcTnT(1) expression. Substituting total cTnT charge for hcTnT(1)
      expression resulted in similar conclusions. Morphometric analysis and electron
      microscopy revealed no differences between wild-type (non-TG) and TG myocardium.
      No differences in isoform expression of tropomyosin, myosin heavy chain,
      essential and regulatory myosin light chains (MLC), TnI, or in posttranslational
      modifications of mouse cTnT, cTnI, or regulatory MLC were observed. These results
      support the hypothesis that cTnT isoform amino-terminal differences affect
      myofilament function and suggest that hcTnT(1) expression levels present during
      human development and in human heart disease can affect in vivo ventricular
      function.

PMID- 15513966
TI  - MUC1 (CD227) interacts with lck tyrosine kinase in Jurkat lymphoma cells and
      normal T cells.
AB  - MUC1 (CD227) is a large transmembrane epithelial mucin glycoprotein, which is
      aberrantly overexpressed in most adenocarcinomas and is a target for immune
      therapy for epithelial tumors. Recently, MUC1 has been detected in a variety of
      hematopoietic cell malignancies including T and B cell lymphomas and myelomas;
      however, its function in these cells is not clearly defined. Using the Jurkat T
      cell lymphoma cell line and normal human T cells, we demonstrate that MUC1 is not
      only expressed in these cells but is also phosphorylated upon T cell receptor
      (TCR) ligation and associates with the Src-related T cell tyrosine kinase,
      p56lck. Upon TCR-mediated activation of Jurkat cells, MUC1 is found in the low
      density membrane fractions, where linker of T cell activation is contained.
      Abrogation of MUC1 expression in Jurkat cells by MUC1-specific small interfering
      RNA resulted in defects in TCR-mediated downstream signaling events associated
      with T cell activation. These include reduction in Ca2+ influx and extracellular
      signal-regulated kinase 1/2 phosphorylation, leading to a decrease in CD69
      expression, proliferation, and interleukin-2 production. These results suggest a
      regulatory role of MUC1 in modulating proximal signal transduction events through
      its interaction with proteins of the activation complex.

PMID- 15513967
TI  - Identification of a novel tumor necrosis factor alpha-responsive region in the
      NCF2 promoter.
AB  - The phagocyte reduced nicotinamide adenine dinucleotide phosphate oxidase is a
      multiprotein enzyme that catalyzes the production of microbicidal oxidants.
      Although oxidase assembly involves association of several membrane and cytosolic
      oxidase proteins, one of the cytosolic cofactors, p67phox, appears to play a more
      prominent role in final activation of the enzyme complex. Based on the importance
      of p67phox, we investigated transcriptional regulation of the p67phox gene
      [neutrophil cytosolic factor 2 (NCF2)] and demonstrated previously that activator
      protein-1 (AP-1) was essential for basal transcriptional activity. As p67phox can
      be up-regulated by tumor necrosis factor alpha (TNF-alpha), which activates AP-1,
      we hypothesized that TNF-alpha might regulate NCF2transcription via AP-1. In
      support of this hypothesis, we show here that NCF2 promoter-reporter constructs
      are up-regulated by TNF-alpha but only when AP-1 factors were coexpressed.
      Consistent with this observation, we also demonstrate that NCF2 mRNA and p67phox
      protein are up-regulated by TNF-alpha in various myeloid cell lines as well as in
      human monocytes. It was surprising that mutagenesis of the AP-1 site in NCF2
      promoter constructs did not eliminate TNF-alpha induction, suggesting additional
      elements were involved in this response and that AP-1 might play a more indirect
      role. Indeed, we used NCF2 promoter-deletion constructs to map a novel TNF-alpha
      responsive region (TRR) located between -56 and -16 bp upstream of the
      translational start site and demonstrated its importance in vivo using
      transcription factor decoy analysis. Furthermore, DNase footprinting verified
      specific binding of factor(s) to the TRR with AP-1 binding indirectly to this
      region. Thus, we have identified a novel NCF2 promoter/enhancer domain, which is
      essential for TNF-alpha-induced up-regulation of p67phox.

PMID- 15513968
TI  - Commentary: The child is the mother of the woman: Intergenerational associations
      in maternal anthropometry.

PMID- 15513969
TI  - Commentary: Difficulties in disentangling causes of social class inequities in
      musculoskeletal health.

PMID- 15513970
TI  - Irish injecting drug users and hepatitis C: the importance of the social context
      of injecting.
AB  - BACKGROUND: The incidence of hepatitis C (HCV) infection among injecting drug
      users (IDUs) in Dublin is particularly high by international standards. The most
      robust predictor of an IDU's HCV status is his or her total number of lifetime
      injecting episodes. It has been proposed that participation in specific unsafe
      injecting practices is the principal contributor to this accumulated risk. We
      sought to test this hypothesis. The relationship between social context of
      injecting and HCV status was also examined. METHODS: We conducted a cross
      sectional survey of IDUs recruited from treatment settings in Dublin.
      Participants had injected in the preceding six months and had not previously been
      tested for HCV. A structured interview was conducted. RESULTS: HCV testing was
      performed on 159 IDUs, and 61% were antibody positive. The three characteristics
      that were significant independent predictors of a positive test result were
      increased total number of lifetime injecting episodes, closer social
      relationships with other IDUs, and injecting in the home of other IDUs. Frequency
      of recipient syringe sharing (i.e. borrowing used syringes from other IDUs),
      backloading, and sharing of injecting paraphernalia were not independently
      associated with infection. CONCLUSIONS: We found that the robust association
      between HCV infection and number of lifetime injecting episodes was not explained
      by increased unsafe injecting practices. The socialized nature of heroin
      injecting in Dublin is contributing to the HCV epidemic in this population. Our
      findings suggest that accidental and unnoticed sharing of injecting equipment may
      be an important contributor to an IDU's increasing risk of infection over time.

PMID- 15513971
TI  - The influence of factors identified in adolescence and early adulthood on social
      class inequities of musculoskeletal disorders at age 30: a prospective population
      based cohort study.
AB  - BACKGROUND: Social class inequities have been observed for most measures of
      health. A greater understanding of the relative importance of different
      explanations is required. In this prospective population-based cohort study we
      explored the contribution of factors, ascertained at different stages between
      adolescence and early adulthood, to social class inequities in musculoskeletal
      disorders (MSD) at age 30. METHODS: We used data from 547 men and 497 women from
      a town in north Sweden who were baseline examined at age 16 and followed up to
      age 30. Using logistic regression models, we estimated the unadjusted odds ratios
      (OR) for MSD for blue-collar versus white-collar workers in men and women
      separately. We assessed the contribution of different factors identified between
      adolescence and early adulthood by comparing the unadjusted OR for social class
      differences with OR adjusted for these explanatory factors. RESULTS: We found
      significant class differences at age 30 with higher MSD among blue-collar workers
      (OR = 2.03 in men [95% CI: 1.42, 2.90] and 1.98 in women [95% CI: 1.29, 3.02]).
      After adjustment for explanatory factors, class differences decreased and were no
      longer significant, with OR of 1.20 in men (95% CI: 0.76, 1.95) and 1.18 in women
      (95% CI: 0.69, 2.03). School grades at age 16; being single and alcohol
      consumption at age 21; having children, restricted financial resources, physical
      activity, alcohol consumption, smoking, and working conditions at age 30 were
      important for men; parents' social class, school grade, smoking and physical
      activity at age 16; being single at age 21; and working conditions at age 30 were
      important for women. CONCLUSION: The accumulation of adverse behavioural and
      social circumstances from adolescence to early adulthood may be an explanation
      for the class differences in MSD at age 30. Interventions aimed at reducing
      health inequities need to consider exploratory factors identified at early and
      later stages in life, also including structural determinants of health.

PMID- 15513972
TI  - Serum and follicular resistin levels in women with polycystic ovarian syndrome
      during IVF-stimulated cycles.
AB  - BACKGROUND: Resistin is a hormone linking obesity and insulin resistance. The aim
      of this study was to compare resistin levels in serum or follicular fluid from
      women with polycystic ovarian syndrome (PCOS) and controls, both of whom were
      undergoing IVF. METHODS: We compared serum and follicular resistin levels in 21
      PCOS women and in 18 healthy, normal ovulation, age- and body mass index (BMI)
      matched non-PCOS women undergoing IVF. Correlations between serum or follicular
      fluid resistin levels and reproductive outcome were evaluated. RESULTS: There was
      no significant difference in either serum or follicular resistin levels between
      the control group and the PCOS group as a whole or those with insulin resistance
      [homeostasis model assessment of insulin resistance index applied to oral glucose
      tolerance test (HOMA(OGTT)) <4.7]. However, resistin levels in follicular fluid
      were unexpectedly significantly lower than serum levels (P<0.0001) in both the
      PCOS and control groups. No significant correlation was found between resistin
      levels and BMI, estradiol, LH, or fasting or 2 h glucose or insulin levels or
      between follicular resistin levels and fertilization rate, implantation rate,
      clinical pregnancy rate, or early miscarriage rate in PCOS. CONCLUSION: Resistin
      is unlikely to be a major determining factor in the growth and maturation of
      oocytes during IVF-stimulated cycles in PCOS.

PMID- 15513973
TI  - A successful pregnancy outcome using frozen testicular sperm from a chimeric
      infertile male with a 46, XX/46, XY karyotype: case report.
AB  - BACKGROUND: We report a very rare case of the successful delivery of a healthy
      infant fathered by an infertile chimera. METHODS: ICSI was performed using frozen
      sperm. The karyotypes of peripheral lymphocytes were examined with a G-banding
      stain. RESULTS: Chromosomal analysis prior to ICSI revealed a 46, XX [28]/46, XY
      [2] karyotype chimera. As an infant, the subject was diagnosed as a true
      hermaphrodite, and underwent a hysterectomy and oophorectomy. A small number of
      sperm were found in minced testicular tissue, and they were stored for ICSI.
      CONCLUSION: To the best of our knowledge, this is the first case report of a
      successful pregnancy and delivery of a healthy infant fathered by an infertile
      chimera (46, XX/46, XY) following ICSI using frozen testicular sperm.

PMID- 15513974
TI  - High frequency of gr/gr chromosome Y deletions in consecutive oligospermic ICSI
      candidates.
AB  - BACKGROUND: The Y chromosome gr/gr microdeletion eliminates two copies of the DAZ
      gene and several additional transcriptional units and has been associated as a
      risk factor for infertility. Our objective was to study the presence of the gr/gr
      deletion in ICSI candidates in our population and to determine whether the
      laboratory, clinical and ICSI outcome were different in the gr/gr deleted
      patients. METHODS: Two hundred and eighty-three ICSI candidates were studied.
      Semen analysis, serum FSH, LH, testosterone, inhibin B, karyotype and detection
      of sequence tagged sites in the Y chromosome were performed. RESULTS: gr/gr
      deletions were detected in 11 (5.07%) of 217 oligospermic and in one (1.52%) of
      66 azoospermic consecutive ICSI candidates, but in none of 232 controls
      (P=0.002). The fertility rate was not different in the four patients of the gr/gr
      deleted group treated by ICSI (64.38%; 47/73) as compared to average results at
      our center (65.49%; 2393/3654). CONCLUSIONS: gr/gr deletions are a risk factor
      for spermatogenic failure at our population, but the prognosis of the four
      patients of the gr/gr deleted group treated by ICSI is not different from that of
      other ICSI patients.

PMID- 15513975
TI  - Comparison of the effects of acarbose and metformin use on ovulation rates in
      clomiphene citrate-resistant polycystic ovary syndrome.
AB  - BACKGROUND: The aim of this study was to evaluate the effects of metformin and
      acarbose on insulin resistance, hormone profiles and ovulation rates in patients
      with clomiphene citrate-resistant polycystic ovary syndrome (PCOS). METHODS:
      Thirty clomiphene citrate-resistant patients were selected randomly and divided
      into two groups. Group I was treated with 100 mg/day clomiphene citrate and 300
      mg/day acarbose 100 mg/day orally, for 3 months. Group II was treated with
      clomiphene citrate 100 mg/day and metformin 1700 mg/day orally, for 3 months.
      Serum fasting insulin and glucose, FSH, LH, estradiol, progesterone, prolactin
      and total testosterone levels plus body mass index (BMI) were measured before and
      after treatment. Follicle growth was followed by transvaginal ultrasonography.
      RESULTS: LH:FSH ratio and total testosterone concentrations decreased (P<0.05)
      and ovulation rates increased in both groups. Reduction in weight and BMI was
      only significant in the acarbose group. CONCLUSIONS: Both treatment modalities
      were effective in the treatment of insulin resistance and improving ovulation
      rates. Increase in the number of eumenorrhoeic and normoinsulinaemic cases and
      decrease in the number of insulin-resistant cases were significant in both groups
      (P<0.05). Ovulation rate was greater in the metformin group in the second month
      of therapy (P<0.05). Acarbose was found to be a safe and effective agent that
      could be used in cases with clomiphene-resistant PCOS.

PMID- 15513976
TI  - Environmental PCB exposure and risk of endometriosis.
AB  - BACKGROUND: Hormonally active environmental agents have recently been associated
      with the development of endometriosis. METHODS: We undertook a study to assess
      the relationship between endometriosis, an estrogen-dependent gynaecological
      disease, and 62 individual polychlorinated biphenyl (PCBs) congeners. We enrolled
      84 eligible women aged 18-40 years undergoing laparoscopy for study, which
      included an interview and blood specimen (n=79; 94%). Thirty-two women had
      visually confirmed endometriosis at laparoscopy while 52 did not. Blood specimens
      were run in batches of 14 including four quality control samples for
      toxicological analysis. Each PCB congener was adjusted for recovery; batch
      specific reagent blanks were subtracted. All PCB concentrations were log
      transformed and expressed in ng/g serum first as a sum and then as tertiles by
      purported estrogenic or anti-estrogenic activity of PCB congeners. RESULTS: Using
      unconditional logistic regression analysis, a significantly elevated odds ratio
      (OR) was observed for women in the third tertile of anti-estrogenic PCBs [OR
      3.77; 95% confidence interval (CI) 1.12-12.68]. Risk remained elevated after
      controlling for gravidity, current cigarette smoking and serum lipids (OR 3.30;
      95% CI 0.87-12.46). CONCLUSIONS: These data suggest that anti-estrogenic PCBs may
      be associated with the development of endometriosis.

PMID- 15513977
TI  - The ATAC ('Arimidex', Tamoxifen, Alone or in Combination) adjuvant breast cancer
      trial: baseline endometrial sub-protocol data on the effectiveness of
      transvaginal ultrasonography and diagnostic hysteroscopy.
AB  - BACKGROUND: The 'Arimidex', Tamoxifen, Alone or in Combination (ATAC) trial is a
      randomized, double-blind trial comparing anastrozole ('Arimidex'), alone or in
      combination with tamoxifen, relative to tamoxifen alone as 5 year adjuvant
      treatment for post-menopausal women with early breast cancer. Since tamoxifen is
      associated with endometrial pathology, the ATAC endometrial sub-protocol was
      initiated to establish the background prevalence of intrauterine pathology, and
      to assess prospectively the incidence and nature of intrauterine changes
      following endocrine therapy. Another aim was to provide data from which advice
      could be generated on the best endometrium screening method for patients
      receiving tamoxifen. METHODS: Patients underwent endometrial assessments at entry
      to the sub-protocol. The baseline investigations comprised transvaginal
      ultrasound scanning (TVUS), a hysteroscopy and an endometrial biopsy. RESULTS: A
      total of 285 gynaecologically asymptomatic women from 31 centres in 10 countries
      entered the endometrial sub-protocol. The mean uterine volume was 47.7 cm3. The
      median endometrial thickness overall was 3 mm. Twenty-four histologically
      confirmed, pathological changes were observed. Twenty-three pathologies were
      confirmed by TVUS, and 21 were identified by hysteroscopy and confirmed by
      histopathology. Women with or without intrauterine pathology had median
      endometrial thickness of 5 and 3 mm respectively. CONCLUSIONS: The presence of
      pathology was associated with increased endometrial thickness. The relative
      sensitivity and specificity of hysteroscopy and endometrial thickness for the
      diagnosis of endometrial pathology was comparable to other studies. If screening
      of the endometrium prior to treatment is appropriate, this study supports the use
      of an endometrial thickness of 3 mm, as assessed by TVUS, as a threshold for
      needing further investigation. This study demonstrates that if the endometrial
      thickness is >3 mm, hysteroscopy and biopsy is the optimal method of detecting
      intrauterine pathology in women with breast cancer who are about to commence
      endocrine treatment.

PMID- 15513978
TI  - Cathine and norephedrine, both phenylpropanolamines, accelerate capacitation and
      then inhibit spontaneous acrosome loss.
AB  - BACKGROUND: Cathinone, released when Catha edulis leaves (khat) are chewed, has
      euphoric, stimulatory properties. It is metabolized to the phenylpropanolamines
      (PPAs) cathine and norephedrine. This study investigated whether PPAs affect
      mammalian sperm function, using primarily mouse, but also human, spermatozoa.
      METHODS: Uncapacitated sperm suspensions were treated with cathine, norephedrine,
      adrenaline and noradrenaline, then assessed using chlortetracycline (CTC)
      fluorescence. Cathine and adrenaline were also evaluated using in vitro
      fertilization. Capacitated suspensions were treated with PPAs+/-progesterone
      and+/-pertussis toxin. Finally, cAMP production was evaluated in uncapacitated
      and capacitated suspensions. RESULTS: In uncapacitated mouse spermatozoa,
      cathine, norephedrine, adrenaline and noradrenaline all significantly accelerated
      capacitation; uncapacitated human spermatozoa responded similarly to cathine.
      Consistent with these results, cathine- and adrenaline-treated suspensions were
      significantly more fertile than controls. In capacitated spermatozoa, both PPAs
      inhibited spontaneous acrosome reactions (ARs) but progesterone could over-ride
      this inhibition. Pertussis toxin abolished cathine's inhibition of ARs,
      suggesting G protein involvement. Finally, cathine and adrenaline significantly
      stimulated cAMP production in uncapacitated suspensions, but significantly
      inhibited it in capacitated suspensions. CONCLUSIONS: This is the first
      demonstration that PPAs can directly affect mammalian sperm function,
      accelerating capacitation and inhibiting spontaneous ARs. These responses
      correlated with initial stimulation and subsequent inhibition of cAMP production.
      Adrenaline/noradrenaline elicited similar responses, suggesting the presence of
      adrenergic receptors. Therefore, regulation of adenylyl cyclase/cAMP in a G
      protein-mediated fashion by PPAs may possibly involve adrenergic receptors. These
      results suggest that PPAs, at appropriate doses, might provide a novel approach
      to enhance natural fertility.

PMID- 15513979
TI  - The ovarian markers of the FSH insufficiency in functional hypothalamic
      amenorrhoea.
AB  - BACKGROUND: The purpose of this work was to revisit the gonadotrophin
      insufficiency of functional hypothalamic amenorrhoea (FHA) with the use of
      relevant ovarian markers. METHODS: Serum anti-Mullerian hormone (AMH), estradiol
      (E2), inhibin B, LH and FSH were immunoassayed in 31 women with FHA and in 30
      healthy women in early follicular phase. The ovarian antral follicle number (FN)
      was determined within two distinct diameter ranges (2-5 and 6-9 mm) by ultrasound
      in real time, the same day as the blood sampling. RESULTS: The 2-5 mm FN was
      similar between the two groups, while the 6-9 mm FN was significantly less in FHA
      than in controls, in relation with lower serum FSH levels (r=0.428; P<0.024).
      Nine (29%) FHA patients had a low serum basal FSH level (i.e. <4.5 IU/l, 5th
      percentile of control values). In the 22 (71%) patients with apparently normal
      FSH, the mean 6-9 mm FN was similar to controls. However, in this sub-group, the
      mean AMH serum level and the AMH:2-5 mm FN ratio were significantly higher and
      the mean inhibin B serum level was significantly lower than in controls. No
      significant relationship was found between the serum LH levels and the FN, AMH or
      inhibin B values. CONCLUSION: Only a minority of patients with FHA have a low
      serum basal FSH level, and we show that this is associated with fewer 6-9 mm
      follicles at the ovarian level. Despite a normal serum FSH level and 6-9 mm FN in
      the majority of patients with FHA, the functional follicle markers are abnormal.
      This suggests that the FSH action on the ovary is incomplete and is not properly
      reflected by its serum level nor by FN at ultrasound.

PMID- 15513980
TI  - Increased frequency of migraine among women with endometriosis.
AB  - BACKGROUND: Our aim is to assess the prevalence and characteristics of headache
      in patients with endometriosis compared with women without this disease. METHODS:
      One hundred and thirty-three women with histologically proven endometriosis and
      166 controls were interviewed by a neurologist experienced in headache diagnosis;
      the headache disorders were classified according to the 1988 International
      Headache Society criteria. RESULTS: The prevalence of migraine was significantly
      higher among women with endometriosis [n = 51, 38.3%; 95% confidence interval
      (CI) 30.1-47.2%] than in controls (n = 25, 15.1%; 95% CI 10.0-21.4%) (P < 0.001).
      Migraine with aura was observed in 18 women with endometriosis (13.5%) and in two
      controls (1.2%; P < 0.001). The age at migraine onset was significantly lower in
      women with endometriosis than in controls (16.4 versus 21.9 years; P = 0.001). No
      significant difference was observed in pain intensity and attack frequency
      between the two groups; a trend for women with endometriosis to have longer
      unmedicated attacks was observed. No significant correlation was observed between
      attack frequency, unmedicated headache duration, migraine intensity and the
      severity of endometriosis. CONCLUSION: Migraine is more frequent in women with
      endometriosis than in controls, although its presence and characteristics are not
      related to the severity of endometriosis.

PMID- 15513981
TI  - GnRH agonist stimulation of the pituitary-gonadal axis in children: age and sex
      differences in circulating inhibin-B and activin-A.
AB  - BACKGROUND: Inhibin-B decreases and activin increases FSH secretion in adults. We
      investigated whether an FSH-inhibin/activin feedback loop exists before or during
      puberty. METHODS: FSH secretion was stimulated with 10 microg/kg leuprolide
      acetate (GnRH agonist) in 18 girls, ages 1.0-13.2 years, and 11 boys, ages 8.9
      15.2 years, with variations in pubertal development, and in five normal 9- to 10
      year-old girls. Blood, obtained at 0, 0.5, 1, 2, 4, 8, 12, 16, 20 and 24 h after
      GnRH agonist, was analysed for LH, FSH, activin-A, inhibin-A, inhibin-B,
      follistatin 288 and estradiol/testosterone. RESULTS: FSH increased within 30 min
      of GnRH agonist administration with a peak greater in girls than boys (P=0.0006).
      Baseline inhibin-B was greater in boys than girls (P=0.01), while baseline
      activin-A concentrations were greater in girls. GnRH agonist-stimulated FSH
      increased inhibin-B in girls by 8 h and in boys by 20 h (P<0.05), but did not
      affect activin-A. Inhibin-B increases were seen only in girls older than 5 years.
      CONCLUSIONS: An inhibin-B-FSH feedback loop exists prior to the onset of puberty
      in girls older than 5 years. Sex differences in activin-A and inhibin-B
      concentrations may be responsible for sex differences in serum FSH
      concentrations.

PMID- 15513982
TI  - Impact of the sex of first child on the prognosis in secondary recurrent
      miscarriage.
AB  - BACKGROUND: The carriage of a male fetus often initiates maternal immunological
      reactions against male-specific minor histocompatibility (HY) antigens, which, in
      theory, could result in subsequent recurrent miscarriage (RM). METHODS:
      Information about subsequent pregnancy outcome was procured among 182 women with
      RM after a birth (secondary RM) referred since 1986 using questionnaires,
      telephone interviews and registers. RESULTS: Significantly more of the women had
      had a male first-born as compared with a female first-born (110 versus 72; P <
      0.02). By January 2002, 58% of those who had a male first-born had given birth to
      a second live infant compared with 76% of those who previously had had a female
      first-born (P = 0.01). Women in the former group had a significantly lower chance
      of having a second child than those in the latter (adjusted hazard ratio 0.59;
      95% confidence interval 0.41-0.86). The number of miscarriages after admission
      and the risk of secondary infertility were significantly greater in women with a
      male first-born than among those with a female first-born (P < 0.001 and P =
      0.02; respectively). CONCLUSIONS: A male first-born seems to be associated with a
      less favourable reproductive potential among women with secondary RM. Maternal
      immunization against HY antigens may be responsible for these findings.

PMID- 15513983
TI  - A constitutional complex chromosome rearrangement involving meiotic arrest in an
      azoospermic male: case report.
AB  - Complex chromosome rearrangements are rare aberrations that frequently lead to
      reproductive failure and that may hinder assisted reproduction. A 25-year-old
      azoospermic male was studied cytogenetically with synaptonemal complex analysis
      of spermatocytes from a testicular biopsy and fluorescence in situ hybridization
      (FISH) of lymphocytes. The spermatocytes showed a pentavalent plus a univalent
      chromosome. Cell death occurred mainly at advanced pachytene stages. The sex
      chromosomes were involved in the multiple, as shown by their typical axial
      excrescences. Two autosomal pairs, including an acrocentric chromosome (15), were
      also involved in the multiple. FISH allowed the definite identification of all
      the involved chromosomes. An inverted chromosome 12 is translocated with most of
      one long arm of chromosome 15, while the centromeric piece of this chromosome 15
      is translocated with Yqh, forming a small marker chromosome t(15;Y). The
      euchromatic part of the Y chromosome is joined to the remaining piece of
      chromosome 12, forming a neo-Y chromosome. The patient shows azoospermia and a
      normal phenotype. The disruption of spermatogenesis is hypothetically due to the
      extent of asynaptic segments and to sex-body association during pachytene. This
      CCR occurred 'de novo' during paternal spermatogenesis. Meiotic analysis and FISH
      are valuable diagnostic tools in these cases.

PMID- 15513984
TI  - Legal harmonization and reproductive tourism in Europe.
AB  - Legislation of ethical issues illustrates the uneasy mix of ethics and politics.
      Although the majority has the political right to express its moral views in the
      law, a number of important ethical values like autonomy, tolerance and respect
      for other people's opinions urge the majority to take the minorities' position
      into account. Ignoring pluralism in society will inevitably lead to reproductive
      tourism. Although European legislation and harmonization in the domain of
      medically assisted reproduction is presented as a partial solution to this
      phenomenon, it is argued that European legislation should be avoided as much as
      possible. Regulation of these private ethical matters should be left to the
      national parliaments. A soft or compromise legislation will keep reproductive
      travelling to a minimum. Reproductive tourism is a safety valve that reduces
      moral conflict and expresses minimal recognition of the others' moral autonomy.

PMID- 15513985
TI  - Identifying differentially expressed genes from microarray experiments via
      statistic synthesis.
AB  - MOTIVATION: A common objective of microarray experiments is the detection of
      differential gene expression between samples obtained under different conditions.
      The task of identifying differentially expressed genes consists of two aspects:
      ranking and selection. Numerous statistics have been proposed to rank genes in
      order of evidence for differential expression. However, no one statistic is
      universally optimal and there is seldom any basis or guidance that can direct
      toward a particular statistic of choice. RESULTS: Our new approach, which
      addresses both ranking and selection of differentially expressed genes,
      integrates differing statistics via a distance synthesis scheme. Using a set of
      (Affymetrix) spike-in datasets, in which differentially expressed genes are
      known, we demonstrate that our method compares favorably with the best individual
      statistics, while achieving robustness properties lacked by the individual
      statistics. We further evaluate performance on one other microarray study.

PMID- 15513986
TI  - Theoretical and practical advances in genome halving.
AB  - MOTIVATION: Duplication of an organism's entire genome is a rare but spectacular
      event, enabling the rapid emergence of multiple new gene functions. Over time,
      the parallel linkage of duplicated genes across chromosomes may be disrupted by
      reciprocal translocations, while the intra-chromosomal order of genes may be
      shuffled by inversions and transpositions. Some duplicate genes may evolve
      unrecognizably or be deleted. As a consequence, the only detectable signature of
      an ancient duplication event in a modern genome may be the presence of various
      chromosomal segments containing parallel paralogous genes, with each segment
      appearing exactly twice in the genome. The problem of reconstructing the linkage
      structure of an ancestral genome before duplication is known as genome halving
      with unordered chromosomes. RESULTS: In this paper, we derive a new upper bound
      on the genome halving distance that is tighter than the best known, and a new
      lower bound that is almost always tighter than the best known. We also define the
      notion of genome halving diameter, and obtain both upper and lower bounds for it.
      Our tighter bounds on genome halving distance yield a new algorithm for
      reconstructing an ancestral duplicated genome. We create a software package
      GenomeHalving based on this new algorithm and test it on the yeast genome,
      identifying a sequence of translocations for halving the yeast genome that is
      shorter than previously conjectured possible.

PMID- 15513987
TI  - GOChase: correcting errors from Gene Ontology-based annotations for gene
      products.
AB  - SUMMARY: The Gene Ontology (GO) is a controlled biological vocabulary that
      provides three structured networks of terms to describe biological processes,
      cellular components and molecular functions. Many databases of gene products are
      annotated using the GO vocabularies. We found that some GO-updating operations
      are not easily traceable by the current biological databases and GO browsers.
      Consequently, numerous annotation errors arise and are propagated throughout
      biological databases and GO-based high-level analyses. GOChase is a set of web
      based utilities to detect and correct the errors in GO-based annotations.

PMID- 15513988
TI  - Normalization of two-channel microarray experiments: a semiparametric approach.
AB  - MOTIVATION: An important underlying assumption of any experiment is that the
      experimental subjects are similar across levels of the treatment variable, so
      that changes in the response variable can be attributed to exposure to the
      treatment under study. This assumption is often not valid in the analysis of a
      microarray experiment due to systematic biases in the measured expression levels
      related to experimental factors such as spot location (often referred to as a
      print-tip effect), arrays, dyes, and various interactions of these effects. Thus,
      normalization is a critical initial step in the analysis of a microarray
      experiment, where the objective is to balance the individual signal intensity
      levels across the experimental factors, while maintaining the effect due to the
      treatment under investigation. RESULTS: Various normalization strategies have
      been developed including log-median centering, analysis of variance modeling, and
      local regression smoothing methods for removing linear and/or intensity-dependent
      systematic effects in two-channel microarray experiments. We describe a method
      that incorporates many of these into a single strategy, referred to as two
      channel fastlo, and is derived from a normalization procedure that was developed
      for single-channel arrays. The proposed normalization procedure is applied to a
      two-channel dose-response experiment.

PMID- 15513989
TI  - Predicting protein localization in budding yeast.
AB  - MOTIVATION: Most of the existing methods in predicting protein subcellular
      location were used to deal with the cases limited within the scope from two to
      five localizations, and only a few of them can be effectively extended to cover
      the cases of 12-14 localizations. This is because the more the locations involved
      are, the poorer the success rate would be. Besides, some proteins may occur in
      several different subcellular locations, i.e. bear the feature of 'multiplex
      locations'. So far there is no method that can be used to effectively treat the
      difficult multiplex location problem. The present study was initiated in an
      attempt to address (1) how to efficiently identify the localization of a query
      protein among many possible subcellular locations, and (2) how to deal with the
      case of multiplex locations. RESULTS: By hybridizing gene ontology, functional
      domain and pseudo amino acid composition approaches, a new method has been
      developed that can be used to predict subcellular localization of proteins with
      multiplex location feature. A global analysis of the proteins in budding yeast
      classified into 22 locations was performed by jack-knife cross-validation with
      the new method. The overall success identification rate thus obtained is 70%. In
      contrast to this, the corresponding rates obtained by some other existing methods
      were only 13-14%, indicating that the new method is very powerful and promising.
      Furthermore, predictions were made for the four proteins whose localizations
      could not be determined by experiments, as well as for the 236 proteins whose
      localizations in budding yeast were ambiguous according to experimental
      observations. However, according to our predicted results, many of these
      'ambiguous proteins' were found to have the same score and ranking for several
      different subcellular locations, implying that they may simultaneously exist, or
      move around, in these locations. This finding is intriguing because it reflects
      the dynamic feature of these proteins in a cell that may be associated with some
      special biological functions.

PMID- 15513990
TI  - Genetic algorithm optimization for pre-processing and variable selection of
      spectroscopic data.
AB  - MOTIVATION: The major difficulties relating to mathematical modelling of
      spectroscopic data are inconsistencies in spectral reproducibility and the black
      box nature of the modelling techniques. For the analysis of biological samples
      the first problem is due to biological, experimental and machine variability
      which can lead to sample size differences and unavoidable baseline shifts.
      Consequently, there is often a requirement for mathematical correction(s) to be
      made to the raw data if the best possible model is to be formed. The second
      problem prevents interpretation of the results since the variables that most
      contribute to the analysis are not easily revealed; as a result, the opportunity
      to obtain new knowledge from such data is lost. METHODS: We used genetic
      algorithms (GAs) to select spectral pre-processing steps for Fourier transform
      infrared (FT-IR) spectroscopic data. We demonstrate a novel approach for the
      selection of important discriminatory variables by GA from FT-IR spectra for
      multi-class identification by discriminant function analysis (DFA). RESULTS: The
      GA selects sensible pre-processing steps from a total of approximately 10(10)
      possible mathematical transformations. Application of these algorithms results in
      a 16% reduction in the model error when compared against the raw data model. GA
      DFA recovers six variables from the full set of 882 spectral variables against
      which a satisfactory DFA model can be formed; thus inferences can be made as to
      the biochemical differences that are reflected by these spectral bands.

PMID- 15513991
TI  - hp-DPI: Helicobacter pylori database of protein interactomes--embracing
      experimental and inferred interactions.
AB  - We implemented a statistical model into our protein interaction database for
      validation of two-hybrid assays of Helicobacter pylori, and prediction of
      putative protein interactions not yet discovered experimentally. To present the
      enormous amount of experimental and inferred protein interaction networking maps,
      the H.pylori Database of Protein Interactomes (hp-DPI) is developed with a
      succinct yet comprehensive visualization tool integrated with annotation from
      Genbank, GO, and KEGG. hp-DPI is first built with, but not limited to, H.pylori
      protein interactions and is expected to naturally include other organisms'
      protein interacting relationships in the future.

PMID- 15513992
TI  - DPRml: distributed phylogeny reconstruction by maximum likelihood.
AB  - MOTIVATION: In recent years there has been increased interest in producing large
      and accurate phylogenetic trees using statistical approaches. However for a large
      number of taxa, it is not feasible to construct large and accurate trees using
      only a single processor. A number of specialized parallel programs have been
      produced in an attempt to address the huge computational requirements of maximum
      likelihood. We express a number of concerns about the current set of parallel
      phylogenetic programs which are currently severely limiting the widespread
      availability and use of parallel computing in maximum likelihood-based
      phylogenetic analysis. RESULTS: We have identified the suitability of
      phylogenetic analysis to large-scale heterogeneous distributed computing. We have
      completed a distributed and fully cross-platform phylogenetic tree building
      program called distributed phylogeny reconstruction by maximum likelihood. It
      uses an already proven maximum likelihood-based tree building algorithm and a
      popular phylogenetic analysis library for all its likelihood calculations. It
      offers one of the most extensive sets of DNA substitution models currently
      available. We are the first, to our knowledge, to report the completion of a
      distributed phylogenetic tree building program that can achieve near-linear
      speedup while only using the idle clock cycles of machines. For those in an
      academic or corporate environment with hundreds of idle desktop machines, we have
      shown how distributed computing can deliver a 'free' ML supercomputer.

PMID- 15513993
TI  - Evolutionary optimization with data collocation for reverse engineering of
      biological networks.
AB  - MOTIVATION: Modern experimental biology is moving away from analyses of single
      elements to whole-organism measurements. Such measured time-course data contain a
      wealth of information about the structure and dynamic of the pathway or network.
      The dynamic modeling of the whole systems is formulated as a reverse problem that
      requires a well-suited mathematical model and a very efficient computational
      method to identify the model structure and parameters. Numerical integration for
      differential equations and finding global parameter values are still two major
      challenges in this field of the parameter estimation of nonlinear dynamic
      biological systems. RESULTS: We compare three techniques of parameter estimation
      for nonlinear dynamic biological systems. In the proposed scheme, the modified
      collocation method is applied to convert the differential equations to the system
      of algebraic equations. The observed time-course data are then substituted into
      the algebraic system equations to decouple system interactions in order to obtain
      the approximate model profiles. Hybrid differential evolution (HDE) with
      population size of five is able to find a global solution. The method is not only
      suited for parameter estimation but also can be applied for structure
      identification. The solution obtained by HDE is then used as the starting point
      for a local search method to yield the refined estimates.

PMID- 15513994
TI  - PDZBase: a protein-protein interaction database for PDZ-domains.
AB  - SUMMARY: PDZBase is a database that aims to contain all known PDZ-domain-mediated
      protein-protein interactions. Currently, PDZBase contains approximately 300 such
      interactions, which have been manually extracted from > 200 articles. The
      database can be queried through both sequence motif and keyword-based searches,
      and the sequences of interacting proteins can be visually inspected through
      alignments (for the comparison of several interactions), or as residue-based
      diagrams including schematic secondary structure information (for individual
      complexes).

PMID- 15513995
TI  - COBrA: a bio-ontology editor.
AB  - COBrA is a Java-based ontology editor for bio-ontologies that distinguishes
      itself from other editors by supporting the linking of concepts between two
      ontologies, and providing sophisticated analysis and verification functions. In
      addition to the Gene Ontology and Open Biology Ontologies formats, COBrA can
      import and export ontologies in the Semantic Web formats RDF, RDFS and OWL.

PMID- 15513996
TI  - Finding regulatory modules through large-scale gene-expression data analysis.
AB  - MOTIVATION: The use of gene microchips has enabled a rapid accumulation of gene
      expression data. One of the major challenges of analyzing this data is the
      diversity, in both size and signal strength, of the various modules in the gene
      regulatory networks of organisms. RESULTS: Based on the iterative signature
      algorithm [Bergmann,S., Ihmels,J. and Barkai,N. (2002) Phys. Rev. E 67, 031902],
      we present an algorithm-the progressive iterative signature algorithm (PISA)
      that, by sequentially eliminating modules, allows unsupervised identification of
      both large and small regulatory modules. We applied PISA to a large set of yeast
      gene-expression data, and, using the Gene Ontology database as a reference, found
      that the algorithm is much better able to identify regulatory modules than
      methods based on high-throughput transcription-factor binding experiments or on
      comparative genomics.

PMID- 15513997
TI  - Clustering of gene expression data using a local shape-based similarity measure.
AB  - MOTIVATION: Microarray technology enables the study of gene expression in large
      scale. The application of methods for data analysis then allows for grouping
      genes that show a similar expression profile and that are thus likely to be co
      regulated. A relationship among genes at the biological level often presents
      itself by locally similar and potentially time-shifted patterns in their
      expression profiles. RESULTS: Here, we propose a new method (CLARITY; Clustering
      with Local shApe-based similaRITY) for the analysis of microarray time course
      experiments that uses a local shape-based similarity measure based on Spearman
      rank correlation. This measure does not require a normalization of the expression
      data and is comparably robust towards noise. It is also able to detect similar
      and even time-shifted sub-profiles. To this end, we implemented an approach
      motivated by the BLAST algorithm for sequence alignment. We used CLARITY to
      cluster the times series of gene expression data during the mitotic cell cycle of
      the yeast Saccharomyces cerevisiae. The obtained clusters were related to the
      MIPS functional classification to assess their biological significance. We found
      that several clusters were significantly enriched with genes that share similar
      or related functions.

PMID- 15513998
TI  - Extracting relations between promoter sequences and their strengths from
      microarray data.
AB  - MOTIVATION: The relations between the promoter sequences and their strengths were
      extensively studied in the 1980s. Although these studies uncovered strong
      sequence-strength correlations, the cost of their elaborate experimental methods
      have been too high to be applied to a large number of promoters. On the contrary,
      a recent increase in the microarray data allows us to compare thousands of gene
      expressions with their DNA sequences. RESULTS: We studied the relations between
      the promoter sequences and their strengths using the Escherichia coli microarray
      data. We modeled those relations using a simple weight matrix, which was
      optimized with a novel support vector regression method. It was observed that
      several non-consensus bases in the '-35' and '-10' regions of promoter sequences
      act positively on the promoter strength and that certain consensus bases have a
      minor effect on the strength. We analyzed outliers for which the observed gene
      expressions deviate from the promoter strength predictions, and identified
      several genes with enhanced expressions due to multiple promoters and genes under
      strong regulation by transcription factors. Our method is applicable to other
      procaryotes for which both the promoter sequences and the microarray data are
      available.

PMID- 15513999
TI  - Comparison of computational methods for the identification of cell cycle
      regulated genes.
AB  - MOTIVATION: DNA microarrays have been used extensively to study the cell cycle
      transcription programme in a number of model organisms. The Saccharomyces
      cerevisiae data in particular have been subjected to a wide range of
      bioinformatics analysis methods, aimed at identifying the correct and complete
      set of periodically expressed genes. RESULTS: Here, we provide the first thorough
      benchmark of such methods, surprisingly revealing that most new and more
      mathematically advanced methods actually perform worse than the analysis
      published with the original microarray data sets. We show that this loss of
      accuracy specifically affects methods that only model the shape of the expression
      profile without taking into account the magnitude of regulation. We present a
      simple permutation-based method that performs better than most existing methods.

PMID- 15514000
TI  - A novel means of using gene clusters in a two-step empirical Bayes method for
      predicting classes of samples.
AB  - MOTIVATION: The classification of samples using gene expression profiles is an
      important application in areas such as cancer research and environmental health
      studies. However, the classification is usually based on a small number of
      samples, and each sample is a long vector of thousands of gene expression levels.
      An important issue in parametric modeling for so many gene expression levels is
      the control of the number of nuisance parameters in the model. Large models often
      lead to intensive or even intractable computation, while small models may be
      inadequate for complex data. METHODOLOGY: We propose a two-step empirical Bayes
      classification method as a solution to this issue. At the first step, we use the
      model-based cluster algorithm with a non-traditional purpose of assigning gene
      expression levels to form abundance groups. At the second step, by assuming the
      same variance for all the genes in the same group, we substantially reduce the
      number of nuisance parameters in our statistical model. RESULTS: The proposed
      model is more parsimonious, which leads to efficient computation under an
      empirical Bayes estimation procedure. We consider two real examples and simulate
      data using our method. Desired low classification error rates are obtained even
      when a large number of genes are pre-selected for class prediction.

PMID- 15514001
TI  - BACCardI--a tool for the validation of genomic assemblies, assisting genome
      finishing and intergenome comparison.
AB  - SUMMARY: We provide the graphical tool BACCardI for the construction of virtual
      clone maps from standard assembler output files or BLAST based sequence
      comparisons. This new tool has been applied to numerous genome projects to solve
      various problems including (a) validation of whole genome shotgun assemblies, (b)
      support for contig ordering in the finishing phase of a genome project, and (c)
      intergenome comparison between related strains when only one of the strains has
      been sequenced and a large insert library is available for the other. The
      BACCardI software can seamlessly interact with various sequence assembly
      packages. MOTIVATION: Genomic assemblies generated from sequence information need
      to be validated by independent methods such as physical maps. The time-consuming
      task of building physical maps can be circumvented by virtual clone maps derived
      from read pair information of large insert libraries.

PMID- 15514002
TI  - Relation between weight matrix and substitution matrix: motif search by
      similarity.
AB  - MOTIVATION: The discovery of patterns shared by several sequences that differ
      greatly is a basic task in sequence analysis, and still a challenge. Several
      methods have been developed for detecting patterns. Methods commonly used for
      motif search include the Gibbs sampler, Expectation-Maximization (EM) algorithm
      and some intuitive greedy approaches. One cannot guarantee the optimality of the
      result produced by the Gibbs sampler in a single run. The deterministic EM
      methods tend to get trapped by local optima. Solutions found by greedy approaches
      are rarely sufficiently good. RESULTS: A simple model describing a motif or a
      portion of local multiple sequence alignment is the weight matrix model, in which
      a motif is characterized with position-specific probabilities. Two substitution
      matrices are proposed to relate the sequence similarity with the weight matrix.
      Combining the substitution matrix and weight matrix, we examine three typical
      sets of protein sequences with increasing complexity. At a low score threshold
      for pair similarity, sliding windows are compared with a seed window to find the
      score sum, which provides a measure of statistical significance for multiple
      sequence comparison. Such a similarity analysis reveals many aspects of motifs.
      Blocks determined by similarity can be used to deduce a primary weight matrix or
      an improved substitution matrix. The algorithm successfully obtains the optimal
      solution for the test sets by just greedy iteration.

PMID- 15514003
TI  - Superior feature-set ranking for small samples using bolstered error estimation.
AB  - MOTIVATION: Ranking feature sets is a key issue for classification, for instance,
      phenotype classification based on gene expression. Since ranking is often based
      on error estimation, and error estimators suffer to differing degrees of
      imprecision in small-sample settings, it is important to choose a computationally
      feasible error estimator that yields good feature-set ranking. RESULTS: This
      paper examines the feature-ranking performance of several kinds of error
      estimators: resubstitution, cross-validation, bootstrap and bolstered error
      estimation. It does so for three classification rules: linear discriminant
      analysis, three-nearest-neighbor classification and classification trees. Two
      measures of performance are considered. One counts the number of the truly best
      feature sets appearing among the best feature sets discovered by the error
      estimator and the other computes the mean absolute error between the top ranks of
      the truly best feature sets and their ranks as given by the error estimator. Our
      results indicate that bolstering is superior to bootstrap, and bootstrap is
      better than cross-validation, for discovering top-performing feature sets for
      classification when using small samples. A key issue is that bolstered error
      estimation is tens of times faster than bootstrap, and faster than cross
      validation, and is therefore feasible for feature-set ranking when the number of
      feature sets is extremely large.

PMID- 15514004
TI  - Inference of S-system models of genetic networks using a cooperative
      coevolutionary algorithm.
AB  - MOTIVATION: To resolve the high-dimensionality of the genetic network inference
      problem in the S-system model, a problem decomposition strategy has been
      proposed. While this strategy certainly shows promise, it cannot provide a model
      readily applicable to the computational simulation of the genetic network when
      the given time-series data contain measurement noise. This is a significant
      limitation of the problem decomposition, given that our analysis and
      understanding of the genetic network depend on the computational simulation.
      RESULTS: We propose a new method for inferring S-system models of large-scale
      genetic networks. The proposed method is based on the problem decomposition
      strategy and a cooperative coevolutionary algorithm. As the subproblems divided
      by the problem decomposition strategy are solved simultaneously using the
      cooperative coevolutionary algorithm, the proposed method can be used to infer
      any S-system model ready for computational simulation. To verify the
      effectiveness of the proposed method, we apply it to two artificial genetic
      network inference problems. Finally, the proposed method is used to analyze the
      actual DNA microarray data.

PMID- 15514005
TI  - Transforming property of TEL-FGFR3 mediated through PI3-K in a T-cell lymphoma
      that subsequently progressed to AML.
AB  - We previously reported a novel fusion between TEL and FGFR3 in a patient with
      peripheral T-cell lymphoma with t(4; 12)(p16;p13). Disease in this patient
      subsequently progressed to acute myelogenous leukemia (AML) with the same
      translocation. Sequence analysis of TEL-FGFR3 fusion transcripts suggested that
      these diseases originated from the same multipotent stem cell. To determine the
      transforming property of TEL-FGFR3, we established transfectants of this chimeric
      fusion gene and investigated the major signal pathways of TEL-FGFR3-induced
      transformation using various signal transduction inhibitors including SU5402
      (fibroblast growth factor tyrosine kinase [FGFR TK] inhibitor). Our results
      indicated that (1) the expression of TEL-FGFR3 but not DeltaHLH-TEL-FGFR3
      resulted in efficient focus formation in NIH/3T3 cells and conferred interleukin
      3 independence to Ba/F3 cells by a constitutive tyrosine kinase activity probably
      through oligomerization by the HLH domain of TEL; (2) although effector proteins
      including classical mitogen-activated protein kinase (MAPK), p38 MAPK,
      phosphatidylinositol 3-kinase (PI3-K), mammalian target or rapamycin (mTOR),
      signal transducer and activator of transcription 3 (STAT-3) and STAT-5 were
      activated in TEL-FGFR3 transformants, the growth of the transformants was
      inhibited by SU5402 (concentration that inhibits 50% [IC5)]=5 microM) and the PI3
      K inhibitor, LY294002 (IC5)=10 microM) and wortmannin (IC50=5 microM), but not by
      U0126, SB203580, or rapamycin; and (3) injection of TEL-FGFR3 transformants
      induced lethal leukemia into syngeneic mice. Taken together, the leukemogenic
      potential of TEL-FGFR3 may be mediated in part through PI3-K.

PMID- 15514006
TI  - Combination of the histone deacetylase inhibitor LBH589 and the hsp90 inhibitor
      17-AAG is highly active against human CML-BC cells and AML cells with activating
      mutation of FLT-3.
AB  - Present studies show that LBH589, a novel cinnamic hydroxamic acid analog histone
      deacetylase inhibitor, induces acetylation of histone H3 and H4 and of heat shock
      protein 90 (hsp90), increases p21 levels, as well as induces cell-cycle G(1)
      phase accumulation and apoptosis of the human chronic myeloid leukemia blast
      crisis (CML-BC) K562 cells and acute leukemia MV4-11 cells with the activating
      length mutation of FLT-3. In MV4-11 cells, this was associated with marked
      attenuation of the protein levels of p-FLT-3, FLT-3, p-AKT, and p-ERK1/2. In K562
      cells, exposure to LBH589 attenuated Bcr-Abl, p-AKT, and p-ERK1/2. Treatment with
      LBH589 inhibited the DNA binding activity of signal transducers and activators of
      transcription 5 (STAT5) in both K562 and MV4-11 cells. The hsp90 inhibitor 17
      allyl-amino-demethoxy geldanamycin (17-AAG) also induced polyubiquitylation and
      proteasomal degradation of FLT-3 and Bcr-Abl by reducing their chaperone
      association with hsp90. Cotreatment with LBH589 and 17-AAG exerted synergistic
      apoptosis of MV4-11 and K562 cells. In the imatinib mesylate (IM)-refractory
      leukemia cells expressing Bcr-Abl with the T315I mutation, treatment with the
      combination attenuated the levels of the mutant Bcr-Abl and induced apoptosis.
      Finally, cotreatment with LBH589 and 17-AAG also induced more apoptosis of IM
      resistant primary CML-BC and acute myeloid leukemia (AML) cells (with activating
      mutation of FLT-3) than treatment with either agent alone.

PMID- 15514007
TI  - The transcriptional program of terminal granulocytic differentiation.
AB  - To characterize the transcriptional program that governs terminal granulocytic
      differentiation in vivo, we performed comprehensive microarray analyses of human
      bone marrow populations highly enriched in promyelocytes (PMs),
      myelocytes/metamyelocytes (MYs), and neutrophils (bm-PMNs). These analyses
      identified 11 310 genes involved in differentiation, of which 6700 were
      differentially regulated, including previously unidentified effector proteins and
      surface receptors of neutrophils. Differentiation of PMs toward MYs was
      accompanied by a marked decline of proliferative and general cellular activity as
      defined by down-regulation of E2 promoter binding factor (E2F) target genes;
      cyclin dependent kinases 2, 4, and 6; and various metabolic, proteasomal, and
      mitochondrial genes. Expression patterns of apoptosis genes indicated death
      control by the p53 pathway in PMs and by death receptor pathways in bm-PMNs.
      Effector proteins critical for host defense were expressed successively
      throughout granulocytic differentiation, whereas receptors and receptor ligands
      essential for the activation of the host defense program were terminally up
      regulated in bm-PMNs. The up-regulation of ligand-receptor pairs, which are
      defined inducers as well as target genes of nuclear factor-kappa B (NF-kappa B),
      suggests a constitutive activation of NF-kappa B in bm-PMNs by autocrine loops.
      Overall, these results define a granulocytic differentiation model governed by a
      highly coordinated fail-safe program, which promotes completion of
      differentiation before cells gain responsiveness toward activating stimuli that
      accompany infections.

PMID- 15514008
TI  - Cutaneous T-cell lymphoma: malignant proliferation of T-regulatory cells.
AB  - Studies in an in vitro model of cutaneous T-cell lymphoma (CTCL) demonstrated
      that CTCL cell proliferation is stimulated by direct contact with autologous,
      immature dendritic cells (DCs), suggesting that CD4(+) CTCL cell division is
      driven by antigens presented by DC major histocompatibility complex (MHC) class
      2. We now report that the T-cell receptor (TCR) of the CD4(+) CTCL cells is
      triggered after interaction with DCs loaded with apoptotic CTCL cells, as shown
      by reduced membrane expression of CD3 and the TCR, up-regulation of cytotoxic T
      lymphocyte antigen-4 (CTLA-4), and calcium mobilization. CTCL cells adopt a T
      regulatory (Treg) phenotype expressing CD25/CTLA-4 and FoxP3 and secreting
      interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta). Treg CTCL
      cells suppress normal T-cell antigen-driven secretion of IL-2 and interferon
      gamma (IFN-gamma). Blocking DC MHC class 2 expression or transport inhibited CTCL
      cell adoption of a Treg phenotype. Allogeneic CTCL cells or normal CD4 T cells
      served as sources of apoptotic material for CTCL cell conversion to a Treg
      phenotype. Conversion of CTCL cells to Treg cells may explain the anergic,
      immunosuppressive nature of the malignancy.

PMID- 15514009
TI  - The platelet glycoprotein Ib-von Willebrand factor interaction activates the
      collagen receptor alpha2beta1 to bind collagen: activation-dependent
      conformational change of the alpha2-I domain.
AB  - Integrin alpha2beta1 (glycoprotein [GP] Ia/IIa) is a major platelet receptor for
      collagen, containing its collagen-binding site within the alpha2 I domain.
      alpha2beta1 changes conformation upon platelet activation, increasing its
      affinity for collagen. We observed that 2 antibodies known to bind within the
      alpha2I domain, 12F1 and 6F1, bound preferentially to adenosine diphosphate (ADP)
      activated platelets. Interestingly, when whole blood was perfused over a surface
      coated with either 12F1 or 6F1, only 6F1 supported the adhesion of unstimulated
      platelets. To test whether the interaction of GP Ib with von Willebrand factor
      (VWF) directly activates alpha2beta1, we used 12F1 as a probe of integrin
      activation. We perfused blood over a surface coated with a mixture of VWF-A1
      domain (a GP Ib ligand) and 12F1 or VWF-A1 and mouse immunoglobulin G (IgG).
      Platelets rolled and did not attach stably on the A1/IgG surface, but they firmly
      bound and covered the A1/12F1 surface. We corroborated that 12F1 binds an active
      conformation of the I domain by showing that it binds with higher affinity to a
      gain-of-function mutant than to either wild-type I domain or a loss-of-function
      mutant. These results strongly suggest that the interaction of platelet GP Ib
      with VWF mediates the activation of alpha2beta1, increasing its affinity for
      collagen.

PMID- 15514010
TI  - Nonsteroidal anti-inflammatory drugs inhibit a Fyn-dependent pathway coupled to
      Rac and stress kinase activation in TCR signaling.
AB  - In addition to their anti-inflammatory properties, nonsteroidal anti-inflammatory
      drugs (NSAIDs) harbor immunosuppressive activities related to their capacity both
      to inhibit cyclooxygenases (COXs) and to act as peroxisome proliferator-activated
      receptor (PPAR) ligands. We have previously shown that the stress-activated
      kinase p38 is a selective target of NSAIDs in T cells. Here we have investigated
      the effect of NSAIDs on the signaling pathway triggered by the T-cell antigen
      receptor (TCR) and leading to stress kinase activation. The results show that
      nonselective and COX-1-selective NSAIDs also block activation of the stress
      kinase c-Jun N-terminal kinase (JNK) and that prostaglandin-E2 (PGE2) reverses
      this block and enhances TCR-dependent JNK activation. Analysis of the activation
      state of the components upstream of p38 and JNK showed that NSAIDs inhibit the
      serine-threonine kinase p21-activated protein kinase 1 (Pak1) and the small
      guanosine 5'-triphosphatase (GTPase) Rac, as well as the Rac-specific guanine
      nucleotide exchanger, Vav. Furthermore, activation of Fyn, which controls Vav
      phosphorylation, is inhibited by NSAIDs, whereas activation of lymphocyte
      specific protein tyrosine kinase (Lck) and of the Lck-dependent tyrosine kinase
      cascade is unaffected. Accordingly, constitutively active Fyn reverses the NSAID
      dependent stress kinase inhibition. The data identify COX-1 as an important early
      modulator of TCR signaling and highlight a TCR proximal pathway selectively
      coupling the TCR to stress kinase activation.

PMID- 15514011
TI  - Generation of CMV-specific T lymphocytes using protein-spanning pools of pp65
      derived overlapping pentadecapeptides for adoptive immunotherapy.
AB  - Cell-mediated immunity is essential for control of human cytomegalovirus (HCMV)
      infection. We used a pool of 138 synthetic overlapping pentadecapeptides
      overspanning the entire pp65 protein to generate polyclonal CMV-specific T-cell
      lines from 12 CMV-seropositive donors inheriting different HLA genotypes.
      Autologous monocyte-derived dendritic cells (DCs) pulsed with this complete pool
      consistently induced highly specific T cells that selectively recognized 1-3
      pentadecapeptides identified by secondary responses to a mapping grid of
      pentadecapeptide subpools with single overlaps. Responses against peptide-loaded
      targets sharing single HLA class I or II alleles identified the restricting HLA
      alleles. HLA-A*0201+ donors consistently responded to pentadecapeptides
      containing HLA-A*0201-binding epitope(aa495-503)NLVPMVATV. T-cell lines from
      other donors contained high frequencies of CD4 and/or CD8 T cells selectively
      reactive against peptides presented by other HLA alleles, including both known
      epitopes such as (aa341-350)QYDPVAALF (HLA-A*2402) as well as unreported epitopes
      such as (aa267-275)HERNGFTVL (HLA-B*4001 and B*4002) and (aa513-523)FFWDANDIYRI
      (HLA-DRB1*1301). These T cells consistently lysed CMV-infected target cells.
      Thus, this approach fosters expansion and selection of HLA-restricted CMV-pp65
      reactive T-cell lines of high specificity that also lyse CMV-infected targets,
      and from a functional and regulatory perspective, may have advantages for
      generating virus-specific T cells for adoptive immunotherapy.

PMID- 15514012
TI  - Human mesenchymal stem cells alter antigen-presenting cell maturation and induce
      T-cell unresponsiveness.
AB  - Infusion of either embryonic or mesenchymal stem cells prolongs the survival of
      organ transplants derived from stem cell donors and prevents graft-versus-host
      disease (GVHD). An in-depth mechanistic understanding of this tolerization
      phenomenon could lead to novel cell-based therapies for transplantation. Here we
      demonstrate that while human mesenchymal stem cells (hMSCs) can promote
      superantigen-induced activation of purified T cells, addition of antigen
      presenting cells (APCs; either monocytes or dendritic cells) to the cultures
      inhibits the T-cell responses. This contact- and dose-dependent inhibition is
      accompanied by secretion of large quantities of interleukin (IL)-10 and aberrant
      APC maturation, which can be partially overridden by the addition of factors that
      promote APC maturation (ie, lipopolysaccharide [LPS] or anti-CD40 monoclonal
      antibody [mAb]). Thus, our data support an immunoregulatory mechanism wherein
      hMSCs inhibit T cells indirectly by contact-dependent induction of regulatory
      APCs with T-cell-suppressive properties. Our data may reveal a physiologic
      phenomenon whereby the development of a distinct APC population is regulated by
      the tissue's cellular microenvironment.

PMID- 15514013
TI  - Normal hematopoiesis is maintained by activated bone marrow CD4+ T cells.
AB  - CD4(+) T cells produce hematopoietic-related cytokines and are essential for
      hematopoiesis stimulation during infection and hematologic recovery after bone
      marrow transplantation. However, it remains unclear if T cells are necessary to
      maintain normal hematopoiesis. We report here that, in T-cell-deficient mice,
      terminal differentiation of myeloid progenitors is defective, resulting in very
      low levels of granulocytes in the periphery. Hematopoiesis is restored after
      thymus graft or reconstitution with CD4(+) T cells but not CD8(+) T cells. Bone
      marrow CD4(+) T cells have an activated phenotype and produce cytokines,
      apparently, in the absence of exogenous stimulation. Transgenic mice carrying T
      cell receptor specific for an ovalbumin peptide presented in the context of a
      specific class II molecule (I-A(d)) (DO11.10 RAG(-/-)) show the same
      hematopoietic deficiency as athymic mice. Their bone marrow CD4(+) T cells are
      not activated, suggesting that hematopoiesis maintenance requires the presence of
      cognate antigen in order to activate bone marrow T-helper cells. In fact, priming
      of transgenic mice with ovalbumin restores normal hematopoiesis. The data show
      that the current concept of "normal hematopoiesis" does not reflect a basal bone
      marrow activity, but it is an antigen-induced state maintained by constant
      activation of bone marrow CD4(+) T cells.

PMID- 15514014
TI  - ZAP-70 directly enhances IgM signaling in chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) B cells that express unmutated immunoglobulin
      heavy-chain variable region genes (IgV(H)) generally express ZAP-70, in contrast
      to normal B cells or most CLL cases with mutated IgV(H). Following IgM ligation,
      ZAP-70+ CLL cells had significantly higher levels of phosphorylated p72(Syk),
      BLNK, and phospholipase-Cgamma (PLCgamma) and had greater[Ca2+]i flux than did
      ZAP-70-negative CLL cases, including unusual ZAP-70-negative cases with unmutated
      IgV(H). IgM ligation of ZAP-70-negative CLL B cells infected with an adenovirus
      vector encoding ZAP-70 induced significantly greater levels of phosphorylated
      p72(Syk), BLNK, and PLCgamma and had greater[Ca2+]i flux than did similarly
      stimulated, noninfected CLL cells or CLL cells infected with a control adenovirus
      vector. We conclude that expression of ZAP-70 in CLL allows for more effective
      IgM signaling in CLL B cells, a feature that could contribute to the relatively
      aggressive clinical behavior generally associated with CLL cells that express
      unmutated IgV(H).

PMID- 15514015
TI  - Single embryo transfer and IVF/ICSI outcome: a balanced appraisal.
AB  - This review considers the value of single embryo transfer (SET) to prevent
      multiple pregnancies (MP) after IVF/ICSI. The incidence of MP (twins and higher
      order pregnancies) after IVF/ICSI is much higher (approximately 30%) than after
      natural conception (approximately 1%). Approximately half of all the neonates are
      multiples. The obstetric, neonatal and long-term consequences for the health of
      these children are enormous and costs incurred extremely high. Judicious SET is
      the only method to decrease this epidemic of iatrogenic multiple gestations.
      Clinical trials have shown that programmes with >50% of SET maintain high overall
      ongoing pregnancy rates ( approximately 30% per started cycle) while reducing the
      MP rate to <10%. Experience with SET remains largely European although the need
      to reduce MP is accepted worldwide. An important issue is how to select patients
      suitable for SET and embryos with a high putative implantation potential. The
      typical patient suitable for SET is young (aged <36 years) and in her first or
      second IVF/ICSI trial. Embryo selection is performed using one or a combination
      of embryo characteristics. Available evidence suggests that, for the overall
      population, day 3 and day 5 selection yield similar results but better than
      zygote selection results. Prospective studies correlating embryo characteristics
      with documented implantation potential, utilizing databases of individual
      embryos, are needed. The application of SET should be supported by other
      measures: reimbursement of IVF/ICSI (earned back by reducing costs), optimized
      cryopreservation to augment cumulative pregnancy rates per oocyte harvest and a
      standardized format for reporting results. To make SET the standard of care in
      the appropriate target group, there is a need for more clinical studies, for
      intensive counselling of patients, and for an increased sense of responsibility
      in patients, health care providers and health insurers.

PMID- 15514016
TI  - Recent advances in the diagnosis and management of congenital adrenal hyperplasia
      due to 21-hydroxylase deficiency.
AB  - Congenital adrenal hyperplasias (CAH) are inherited defects of cortisol
      biosynthesis. More than 90% of CAH are caused by 21-hydroxylase deficiency (21
      OHD), found in 1:10 000 to 1:15 000 live births. Females with 'classical' 21-OHD,
      being exposed to excess androgens prenatally, are born with virilized external
      genitalia. Potentially lethal adrenal insufficiency is characteristic of two
      thirds to three-quarters of patients with the classical salt wasting (SW) form of
      21-OHD. Non-SW 21-OHD may be diagnosed on genital ambiguity in affected females,
      and/or later on the occurrence of androgen excess in both sexes. Non-classical 21
      OHD, detected in > or =1:100 of certain populations, may present as precocious
      pubarche in children or polycystic ovarian syndrome in young women. 21-OHD is
      caused by mutations in the CYP21 gene encoding the steroid 21-hydroxylase enzyme.
      More than 90% of these mutations result from intergenic recombination between
      CYP21 and the closely linked CYP21P pseudogene. The degree to which each mutation
      compromises enzymatic activity is strongly correlated with the clinical severity
      of the disorder. This close association between genotype and phenotype makes it
      possible to predict clinical outcome in affected subjects. The risk of SW and
      prenatal virilization can be estimated, and overtreatment can be avoided in
      mildly affected cases. Glucocorticoid and mineralocorticoid replacement therapies
      are the mainstays of treatment, but additional therapies are being developed. A
      first trimester prenatal diagnosis should be proposed in families in whom
      molecular studies have been performed previously. The state of heterozygotism can
      be predicted by hormonal testing and confirmed by molecular studies. Prenatal
      diagnosis by direct mutation detection in previously genotyped families permits
      prenatal treatment of affected females in order to avoid or minimize genital
      virilization. Neonatal screening by hormonal methods identifies affected children
      before SW crises develop, reducing mortality in this disorder.

PMID- 15514017
TI  - The introduction of QF-PCR in prenatal diagnosis of fetal aneuploidies: time for
      reconsideration.
AB  - Quantitative fluorescent polymerase chain reaction (QF-PCR) has recently entered
      the field of prenatal diagnosis to overcome the need to culture fetal cells,
      hence to allow rapid diagnosis of some selected chromosomal anomalies. We
      reviewed the studies on the accuracy of QF-PCR in detecting chromosomal anomalies
      at prenatal diagnosis. Overall, 22 504 samples have been analysed. The detection
      rate of aneuploidies of the selected chromosomes (13, 18 and 21, and X and Y) was
      98.6% (95% confidence interval 97.8-99.3). QF-PCR might play a major role and be
      considered a valid alternative to the full karyotype. Being less expensive, and
      almost entirely automated, more women could undergo invasive prenatal diagnosis
      without significant increase in health expenditure. By using QF-PCR as a stand
      alone test, the chances of non diagnosing the commonest, and the only chromosome
      anomalies which do increase in frequency with maternal age, are approximately one
      in 150 abnormal karyotypes, or one in 10-30 000 samples, based on the age
      distribution. These error rates might be deemed acceptable, although most
      structural chromosomal anomalies will be missed. At present, women are rarely
      informed about the full spectrum of the conditions which might be diagnosed via
      amniocentesis or chorionic villous sampling. Some of these anomalies might be
      acceptable, in view of their limited or uncertain clinical relevance, and
      decision analysis might, in the majority of cases, confine the full karyotype to
      selected women who have specific indications.

PMID- 15514018
TI  - Heterogeneity explains features of "anomalous" thermodynamics and statistics.
AB  - Phenomena characterized by power-law probability distributions abound in nature
      and the applied sciences. We show that many of these power laws are well
      described by the Student, or t, distribution, and we discuss the origin of this
      universality based on three examples (Brownian motion, Knudsen diffusion in rough
      pores, and bubbly multiphase flow). These case studies are representative for a
      large class of systems with heterogeneous features, examples of which can be
      found from Earth sciences to astrophysics, and even in the social sciences. We
      show that common forms of polydispersity, such as polydispersity arising
      naturally as a result of aggregation-fragmentation phenomena, typically lie at
      the basis of the observed scaling. We conclude that complicated arguments based
      on long-range correlations or nonergodicity are often incorrect or misleading in
      explaining many naturally observed power laws and, in particular, those described
      by the Student distribution.

PMID- 15514019
TI  - Loss of Runx3 function in leukocytes is associated with spontaneously developed
      colitis and gastric mucosal hyperplasia.
AB  - RUNX transcription factors are key regulators of lineage-specific gene expression
      and might be involved in autoimmune diseases. Runx3 plays a role during the
      development of sensory neurons and T cells and regulates transforming growth
      factor beta (TGF-beta) signaling in dendritic cells. Here, we report that at 4
      weeks of age, Runx3 knockout (KO) mice spontaneously develop inflammatory bowel
      disease (IBD) characterized by leukocyte infiltration, mucosal hyperplasia,
      formation of lymphoid clusters, and increased production of IgA. Additionally, at
      a considerably older age (8 months), the KO mice also develop progressive
      hyperplasia of the gastric mucosa associated with disturbed epithelial
      differentiation and cellular hyaline degeneration. Analysis of cytokines in the
      colonic mucosa of Runx3 KO mice revealed a mixed T helper 1/T helper 2 response.
      By using immunohistochemistry and RNA in situ hybridization, Runx3 expression in
      the gastrointestinal tract is detected in lymphoid and myeloid populations but
      not in the epithelium. The data indicate that loss of leukocytic cell-autonomous
      function of Runx3 results in IBD and gastric lesion in the KO mice. IBD in humans
      is viewed as a complex genetic disorder. Several susceptibility loci were
      identified on different human chromosomes including the chromosomal region 1p36
      where RUNX3 resides. It is thus tempting to speculate that mutations in RUNX3 may
      constitute an IBD risk factor in humans.

PMID- 15514020
TI  - Centromere-encoded RNAs are integral components of the maize kinetochore.
AB  - RNA is involved in a variety of chromatin modification events, ranging from large
      scale structural rearrangements to subtle local affects. Here, we extend the
      evidence for RNA-chromatin interactions to the centromere core. The data indicate
      that maize centromeric retrotransposons (CRMs) and satellite repeats (CentC) are
      not only transcribed, but that nearly half of the CRM and CentC RNA is tightly
      bound to centromeric histone H3 (CENH3), a key inner kinetochore protein. RNAs
      from another tandem repeat (180-bp knob sequence) or an abundant euchromatic
      retroelement (Opie) are undetectable within the same anti-CENH3 immune complexes.
      Both sense and antisense strands of CRM and CentC, but not small interfering RNAs
      homologous to either repeat, were found to coimmunoprecipitate with CENH3. The
      bulk of the immunoprecipitated RNA ranged in size from 40 to 200 nt. These data
      provide evidence for a pool of protected, single-stranded centromeric RNA within
      the centromere/kinetochore complex.

PMID- 15514021
TI  - Evidence that the cysteine-rich domain of Drosophila Frizzled family receptors is
      dispensable for transducing Wingless.
AB  - Members of the Frizzled family of serpentine transmembrane receptors are required
      to transduce Wingless/Int (Wnt) signals and contain in their N-terminal regions a
      conserved Wnt-binding cysteine-rich domain (CRD). Each CRD has specific
      affinities for particular Wnts, and it is generally believed that signal
      transduction depends on the strength of this interaction. Here, we report in vivo
      evidence that the CRD is dispensable for Frizzled family receptors to transduce
      Wingless (Wg), the primary Wnt signal in Drosophila. Thus, we infer that signal
      transduction does not require binding of Wg to the CRD, but instead depends on
      interactions between Wg and other portions of the receptor, or other proteins of
      the receptor complex.

PMID- 15514022
TI  - A locking mechanism preventing radical damage in the absence of substrate, as
      revealed by the x-ray structure of lysine 5,6-aminomutase.
AB  - Lysine 5,6-aminomutase is an adenosylcobalamin and pyridoxal-5'-phosphate
      dependent enzyme that catalyzes a 1,2 rearrangement of the terminal amino group
      of dl-lysine and of l-beta-lysine. We have solved the x-ray structure of a
      substrate-free form of lysine-5,6-aminomutase from Clostridium sticklandii. In
      this structure, a Rossmann domain covalently binds pyridoxal-5'-phosphate by
      means of lysine 144 and positions it into the putative active site of a
      neighboring triosephosphate isomerase barrel domain, while simultaneously
      positioning the other cofactor, adenosylcobalamin, approximately 25 A from the
      active site. In this mode of pyridoxal-5'-phosphate binding, the cofactor acts as
      an anchor, tethering the separate polypeptide chain of the Rossmann domain to the
      triosephosphate isomerase barrel domain. Upon substrate binding and
      transaldimination of the lysine-144 linkage, the Rossmann domain would be free to
      rotate and bring adenosylcobalamin, pyridoxal-5'-phosphate, and substrate into
      proximity. Thus, the structure embodies a locking mechanism to keep the
      adenosylcobalamin out of the active site and prevent radical generation in the
      absence of substrate.

PMID- 15514024
TI  - The stochastic piston problem.
AB  - We obtain analytical solutions for the perturbed shock paths induced by time
      varying random motions of a piston moving inside an adiabatic tube of constant
      area. The variance of the shock location grows quadratically with time for early
      times and switches to linear growth for longer times. The analytical results are
      confirmed by stochastic numerical simulations, and deviations for large random
      piston motions are established.

PMID- 15514023
TI  - Mitotic checkpoint function in the formation of gross chromosomal rearrangements
      in Saccharomyces cerevisiae.
AB  - The accumulation of gross chromosomal rearrangements (GCRs) is characteristic of
      cancer cells. Multiple pathways that prevent GCRs, including S-phase cell cycle
      checkpoints, homologous recombination, telomere maintenance, suppression of de
      novo telomere addition, chromatin assembly, and mismatch repair, have been
      identified in Saccharomyces cerevisiae. However, pathways that promote the
      formation of GCRs are not as well understood. Of these, the de novo telomere
      addition pathway and nonhomologous end-joining are the best characterized. Here,
      we demonstrate that defects in the mitotic checkpoint and the mitotic exit
      network can suppress GCRs in strains containing defects that increase the GCR
      rate. These data suggest that functional mitotic checkpoints can play a role in
      the formation of genome rearrangements.

PMID- 15514027
TI  - Phytolith assemblages in grasses native to central Argentina.
AB  - BACKGROUND AND AIMS: Phytolith reference collections are a prerequisite for
      accurate interpretation of soil phytolith assemblages aimed at reconstructing
      past vegetation. In this study a phytolith reference collection has been
      developed for several grasses native to central Argentina: Poa ligularis,
      Piptochaetium napostaense, Stipa clarazii, Stipa tenuis, Stipa tenuissima, Stipa
      eriostachya, Stipa ambigua, Stipa brachychaeta, Pappophorum subbulbosum,
      Digitaria californica, Bothriochloa edwardsiana and Aristida subulata. METHODS:
      For each species, phytoliths present in the leaf blades were classified into 47
      morphotypes, and their relative frequency determined by observing 300-400
      phytoliths per sample (n = 5). Data were analyzed by complete linkage cluster
      analysis, using the Morisita Index as measure of association. KEY RESULTS: The
      results showed differentiation among phytolith assemblages at species level or at
      plant functional type level. Cluster analysis separated C3 from C4 species and
      palatable from non-palatable species. CONCLUSIONS: This study highlights the
      possibility of reconstructing past vegetation in central Argentina grasslands
      through the analysis of soil phytolith assemblages.

PMID- 15514025
TI  - Computerized microfluidic cell culture using elastomeric channels and Braille
      displays.
AB  - Computer-controlled microfluidics would advance many types of cellular assays and
      microscale tissue engineering studies wherever spatiotemporal changes in fluidics
      need to be defined. However, this goal has been elusive because of the limited
      availability of integrated, programmable pumps and valves. This paper
      demonstrates how a refreshable Braille display, with its grid of 320 vertically
      moving pins, can power integrated pumps and valves through localized deformations
      of channel networks within elastic silicone rubber. The resulting computerized
      fluidic control is able to switch among: (i) rapid and efficient mixing between
      streams, (ii) multiple laminar flows with minimal mixing between streams, and
      (iii) segmented plug-flow of immiscible fluids within the same channel
      architecture. The same control method is used to precisely seed cells,
      compartmentalize them into distinct subpopulations through channel
      reconfiguration, and culture each cell subpopulation for up to 3 weeks under
      perfusion. These reliable microscale cell cultures showed gradients of cellular
      behavior from C2C12 myoblasts along channel lengths, as well as differences in
      cell density of undifferentiated myoblasts and differentiation patterns, both
      programmable through different flow rates of serum-containing media. This
      technology will allow future microscale tissue or cell studies to be more
      accessible, especially for high-throughput, complex, and long-term experiments.
      The microfluidic actuation method described is versatile and computer
      programmable, yet simple, well packaged, and portable enough for personal use.

PMID- 15514026
TI  - Curbing the U.S. carbon deficit.
AB  - The U.S. emitted approximately 1.58 petagrams (Pg) of fossil fuel carbon in 2001,
      approximately one-quarter of global CO(2) production. With climate change
      increasingly likely, strategies to reduce carbon emissions and stabilize climate
      are needed, including greater energy efficiency, renewable energy sources,
      geoengineering, decarbonization, and geological and biological sequestration. Two
      of the most commonly proposed biological strategies are restoring organic carbon
      in agricultural soils and using plantations to sequester carbon in soils and
      wood. Here, we compare scenarios of land-based sequestration to emissions
      reductions arising from increased fuel efficiency in transportation, targeting
      ways to reduce net U.S. emissions by 10% ( approximately 0.16 Pg of carbon per
      year). Based on mean sequestration rates, converting all U.S. croplands to no
      till agriculture or retiring them completely could sequester approximately 0.059
      Pg of carbon per year for several decades. Summary data across a range of
      plantations reveal an average rate of carbon storage an order of magnitude larger
      than in agricultural soils; in consequence, one-third of U.S. croplands or 44
      million hectares would be needed for plantations to reach the target of
      approximately 0.16 Pg of carbon per year. For fossil fuel reductions, cars and
      light trucks generated approximately 0.31 Pg of carbon in U.S. emissions in 2001.
      To reduce net emissions by 0.16 Pg of carbon per year, a doubling of fuel
      efficiency for cars and light trucks is needed, a change feasible with current
      technology. Issues of permanence, leakage, and economic potentials are discussed
      briefly, as is the recognition that such scenarios are only a first step in
      addressing total U.S. emissions.

PMID- 15514028
TI  - The role of the storage carbon of cotyledons in the establishment of seedlings of
      Hymenaea courbaril under different light conditions.
AB  - BACKGROUND AND AIMS: Hymenaea courbaril (Leguminosae-Caesalpinioideae) is a tree
      species with wide distribution through all of the Neotropics. It has large seeds
      (approx. 5 g) with non-photosynthetic storage cotyledons rich (40 %) in a cell
      wall polysaccharide (xyloglucan) as a carbon reserve. Because it is found in the
      understorey of tropical forests, it has been considered as a shade-tolerant, late
      secondary species. However, the physiological mechanisms involved in seedling
      establishment, especially regarding the interplay between storage and light
      intensity, are not understood. In this work, the ecophysiological role of this
      carbon cotyledon reserve (xyloglucan) is characterized, emphasizing its effects
      on seedling growth and development during the transition from heterotrophy to
      autotrophy under different light conditions. METHODS: Seedlings of H. courbaril
      were grown in environments with different light intensities, and with or without
      cotyledons detached before xyloglucan mobilization. Development, growth,
      photosynthesis and carbon partitioning (dry mass and [14C]sucrose) were analysed
      in each treatment. KEY RESULTS: The detachment of cotyledons was not important
      for seedling survival, but resulted in a strong restriction (50 % less) of shoot
      growth, which was the main sink for the cotyledon carbon reserves. Carbon
      restriction promoted an early maturation of the photosynthetic apparatus without
      changes in the net CO2 fixation per unit area. The reduced surface area of the
      first leaves in seedlings without cotyledons was evidence of limited growth and
      development of seedlings in low light conditions (22 micromol m(-2) s(-1) photon
      flux). CONCLUSIONS: There is an increase in the importance of storage xyloglucan
      in cotyledons for H. courbaril seedling development as light intensity decreases,
      confirming that this polymer plays a key role in the adaptation of this species
      to establish successfully in the shadowed understorey of the forest.

PMID- 15514029
TI  - Mouse corticotropin-releasing factor receptor type 2alpha gene: isolation,
      distribution, pharmacological characterization and regulation by stress and
      glucocorticoids.
AB  - Effects of the corticotropin-releasing factor (CRF) family of peptides are
      mediated through activation of two receptors, CRF receptor (CRFR) 1 and CRFR2.
      Based on the homology between known mammalian CRFR genes, we have isolated a cDNA
      encoding the mouse CRFR2alpha (mCRFR2alpha) ortholog from brain. The isolated
      cDNA encodes a 411-amino acid protein with high identity to the rat
      (approximately 97%) and human (approximately 93%) receptors. Central and
      peripheral expression of mCRFR2alpha, determined by RT-PCR followed by Southern
      hybridization, revealed that mCRFR2alpha is restricted mainly to brain
      structures, with highest levels in the hypothalamus and olfactory bulb. In situ
      hybridization showed mCRFR2alpha localization in discrete brain regions,
      including the lateral septum and the ventromedial hypothalamus, whereas
      mCRFR2beta is found only in the choroid plexus. Binding and signaling of CRF
      related ligands was studied using COS-M6 or HEK293T cells transiently transfected
      with mCRFR2alpha. Urocortins (Ucns) show different affinities for binding to
      mCRFR2alpha: Ucn 3 binds mCRFR2alpha with approximately 11-fold lower affinity
      than Ucn 2, which displays an affinity similar to Ucn 1 (approximately 1 nm).
      Cyclase activation, determined by intracellular cAMP accumulation and cAMP
      response element-luciferase activity, showed no differences between CRFR2alpha
      and CRFR2beta in response to stimulation by Ucn 1, Ucn 2, and Ucn 3.
      Interestingly, Ucn 3 was less efficacious than Ucn 1 or Ucn 2 in activating MAPK
      (ERK1/2-p44/p42) via CRFR2alpha, but all three Ucns showed equivalent efficacy
      for activating MAPK through mCRFR2beta. We found a significant reduction in
      hypothalamic mCRFR2alpha mRNA levels after acute and chronic restraint stress in
      mice. Hypothalamic mCRFR2alpha gene transcription in mice was inhibited by
      glucocorticoid administration and elevated by adrenalectomy. In addition, we
      demonstrated that the mCRFR2alpha gene is increased in the hypothalamus of the
      CRFR1-null compared with wild type mice. The predicted mCRFR2alpha promoter
      region was isolated and fused to a luciferase reporter gene and found to be
      decreased by glucocorticoids in a dose and time-dependent manner when transfected
      into CATH.a cells. Computer analysis revealed the presence of 23 putative half
      palindromic glucocorticoid response element sequences within 2.4 kb of the
      mCRFR2alpha 5' flanking region. Elucidation of the structure and processing of
      the mCRFR2 gene and examination of the mCRFR2alpha gene regulation in various
      conditions will enable better understanding of the involvement of this receptor
      in the central response to stress in normal and transgenic mice models.

PMID- 15514030
TI  - Global gene expression analysis of estrogen receptor transcription factor cross
      talk in breast cancer: identification of estrogen-induced/activator protein-1
      dependent genes.
AB  - There is a growing body of literature supporting estrogen's ability to affect
      gene expression through a nonclassical pathway, in which estrogen receptor (ER)
      modulates the activity of other transcription factors such as activator protein
      (AP)-1, specificity protein (Sp-1), or nuclear factor-kappaB (NFkappaB). We
      hypothesized that many estrogen-induced genes are dependent on AP-1 for their
      expression and that these genes can be identified using genomic strategies. Using
      cells expressing an inducible cJun dominant negative, we studied the estrogen
      induction of genes under conditions in which AP-1 was normal or blocked. We show
      that the expression of AP-1-dependent genes was inhibited by the cJun dominant
      negative and that AP-1 blockade does not affect mRNA ERalpha expression or
      estrogen induction of estrogen-responsive element activity. Using a microarray
      approach, we then identified 20 new estrogen-induced/AP-1-dependent genes. These
      estrogen-induced/AP-1-dependent genes contain a higher frequency of consensus AP
      1 sites in their promoters and have increased sensitivity to the AP-1 stimulant
      tetradecanoyl phorbol acetate when compared with estrogen-induced genes whose
      expression was not affected by AP-1 blockade. We also show estrogen and AP-1
      dependent recruitment of ER, steroid receptor coactivator-1, and p300 to the
      promoter of these genes by chromatin immunoprecipitation. These studies
      demonstrate that microarrays can be used in a reverse genetics approach to
      predict the functional promoter structure of large numbers of genes that are
      regulated by multiple transcription factors.

PMID- 15514031
TI  - Beta-catenin is involved in insulin-like growth factor 1-mediated transactivation
      of the androgen receptor.
AB  - The androgen-signaling pathway is important for the growth and progression of
      prostate cancer cells. IGF-I and other polypeptide growth factors have been shown
      to be capable of induction of androgen receptor (AR) activation in the absence
      of, or at low levels of, ligand. It has been shown that IGF-I increases the
      cellular level of beta-catenin, an AR coactivator. In this study, we performed
      several experiments to test whether beta-catenin is involved in IGF-I-induced AR
      mediated transcription. We demonstrate that IGF-I enhances the expression of
      endogenous prostate-specific antigen, an AR target gene, and elevates the level
      of cytoplasmic and nuclear beta-catenin in prostate cancer cells. Transfection of
      either wild-type or a constitutively active mutant of the IGF-I receptor augments
      AR-mediated transcription. An antisense construct of beta-catenin that decreases
      the cellular level of beta-catenin can reduce IGF-1 receptor-mediated enhancement
      of AR activity. Moreover, using a pulse-chase experiment, we showed that IGF-I
      enhances the stability of beta-catenin in prostate cancer cells. Our findings
      delineate a novel pathway for IGF-I in modulating androgen signaling through beta
      catenin.

PMID- 15514032
TI  - Androgen receptor (AR) NH2- and COOH-terminal interactions result in the
      differential influences on the AR-mediated transactivation and cell growth.
AB  - Early reports showed that androgen receptor (AR) NH2- and COOH-terminal (N-C)
      interaction was important for full AR function. However, the influence of these
      interactions on the AR in vivo effects remains unclear. Here we tested some AR
      associated peptides and coregulators to determine their influences on AR N-C
      interaction, AR transactivation, and AR coregulator function. The results showed
      that AR coactivators such as ARA70N, gelsolin, ARA54, and SRC-1 can enhance AR
      transactivation but showed differential influences on the N-C interaction. In
      contrast, AR corepressors ARA67 and Rad9 can suppress AR transactivation, with
      ARA67 enhancing and Rad9 suppressing AR N-C interaction. Furthermore, liganded AR
      C terminus-associated peptides can block AR N-C interaction, but only selective
      peptides can block AR transactivation and coregulator function. We found all the
      tested peptides can suppress prostate cancer LNCaP cell growth at different
      levels in the presence of 5alpha-dihydrotestosterone, but only the tested FXXLF
      containing peptides, not FXXMF-containing peptides, can suppress prostate cancer
      CWR22R cell growth. Together, these results suggest that the effects of AR N-C
      interactions may not always correlate with similar effects on AR-mediated
      transactivation and/or AR-mediated cell growth. Therefore, drugs designed by
      targeting AR N-C interaction as a therapeutic intervention for prostate cancer
      treatment may face unpredictable in vivo effects.

PMID- 15514034
TI  - The protein phosphatase calcineurin determines basal parathyroid hormone gene
      expression.
AB  - Calcium and phosphate regulate PTH mRNA stability through differences in binding
      of parathyroid (PT) proteins to a minimal 63-nucleotide (nt) cis-acting
      instability element in its 3'-untranslated region. One of these proteins is
      adenosine-uridine-rich binding factor (AUF1), whose levels are not regulated in
      PT extracts from rats fed the different diets. However, two-dimensional gels
      showed posttranslational modification of AUF1 that included phosphorylation.
      There is no PT cell line, but in HEK 293 cells the 63-nt element is recognized as
      an instability element, and RNA interference for AUF1 decreased human PTH
      secretion in cotransfection experiments. Stably transfected cells with a chimeric
      GH gene containing the PTH 63-nt cis-acting element were used to study the signal
      transduction pathway that regulates AUF1 modification and chimeric gene mRNA
      stability. Cyclosporine A, the calcineurin inhibitor, regulated AUF1
      posttranslationally, and this correlated with an increase in the stability of GH
      PTH 63-nt mRNA but not of the control GH mRNA. Mice with genetic deletion of the
      calcineurin Abeta gene had markedly increased PTH mRNA levels that were still
      regulated by low calcium and phosphorus diets. Therefore, calcineurin regulates
      AUF1 posttranslationally in vitro and PTH gene expression in vivo but still
      allows its physiological regulation by calcium and phosphate.

PMID- 15514033
TI  - Alterations in mitogen-activated protein kinase kinase and extracellular
      regulated kinase signaling in theca cells contribute to excessive androgen
      production in polycystic ovary syndrome.
AB  - We have investigated the involvement of the MAPK signaling pathway in increased
      androgen biosynthesis and CYP17 gene expression in women with polycystic ovary
      syndrome (PCOS). A comparison of MAPK kinase (MEK1/2) and ERK1/2 phosphorylation
      in propagated normal and PCOS theca cells, revealed that MEK1/2 phosphorylation
      was decreased more than 70%, and ERK1/2 phosphorylation was reduced 50% in PCOS
      cells as compared with normal cells. Infection with dominant-negative MEK1
      increased CYP17 mRNA and dehydroepiandrosterone (DHEA) abundance, whereas
      constitutively active MEK1 reduced DHEA production and CYP17 mRNA abundance.
      Similarly, the MEK inhibitor, PD98059, increased CYP17 mRNA accumulation and
      CYP17 promoter activity to levels observed in PCOS cells. Remarkably, in theca
      cells maintained in the complete absence of insulin, ERK1/2 phosphorylation was
      decreased in PCOS theca cells as compared with normal theca cells, and CYP17 mRNA
      and DHEA synthesis were increased in PCOS theca cells. These studies demonstrate
      that in PCOS cells reduced levels of activated MEK1/2 and ERK1/2 are correlated
      with increased androgen production, irrespective of the insulin concentration.
      These findings implicate alterations in the MAPK pathway in the pathogenesis of
      excessive ovarian androgen production in PCOS.

PMID- 15514035
TI  - The genome of bacteriophage T4: an archeological dig.

PMID- 15514037
TI  - Development of an expressed sequence tag (EST) resource for wheat (Triticum
      aestivum L.): EST generation, unigene analysis, probe selection and
      bioinformatics for a 16,000-locus bin-delineated map.
AB  - This report describes the rationale, approaches, organization, and resource
      development leading to a large-scale deletion bin map of the hexaploid (2n = 6x =
      42) wheat genome (Triticum aestivum L.). Accompanying reports in this issue
      detail results from chromosome bin-mapping of expressed sequence tags (ESTs)
      representing genes onto the seven homoeologous chromosome groups and a global
      analysis of the entire mapped wheat EST data set. Among the resources developed
      were the first extensive public wheat EST collection (113,220 ESTs). Described
      are protocols for sequencing, sequence processing, EST nomenclature, and the
      assembly of ESTs into contigs. These contigs plus singletons (unassembled ESTs)
      were used for selection of distinct sequence motif unigenes. Selected ESTs were
      rearrayed, validated by 5' and 3' sequencing, and amplified for probing a series
      of wheat aneuploid and deletion stocks. Images and data for all Southern
      hybridizations were deposited in databases and were used by the coordinators for
      each of the seven homoeologous chromosome groups to validate the mapping results.
      Results from this project have established the foundation for future developments
      in wheat genomics.

PMID- 15514038
TI  - Construction and evaluation of cDNA libraries for large-scale expressed sequence
      tag sequencing in wheat (Triticum aestivum L.).
AB  - A total of 37 original cDNA libraries and 9 derivative libraries enriched for
      rare sequences were produced from Chinese Spring wheat (Triticum aestivum L.),
      five other hexaploid wheat genotypes (Cheyenne, Brevor, TAM W101, BH1146, Butte
      86), tetraploid durum wheat (T. turgidum L.), diploid wheat (T. monococcum L.),
      and two other diploid members of the grass tribe Triticeae (Aegilops speltoides
      Tausch and Secale cereale L.). The emphasis in the choice of plant materials for
      library construction was reproductive development subjected to environmental
      factors that ultimately affect grain quality and yield, but roots and other
      tissues were also included. Partial cDNA expressed sequence tags (ESTs) were
      examined by various measures to assess the quality of these libraries. All ESTs
      were processed to remove cloning system sequences and contaminants and then
      assembled using CAP3. Following these processing steps, this assembly yielded
      101,107 sequences derived from 89,043 clones, which defined 16,740 contigs and
      33,213 singletons, a total of 49,953 "unigenes." Analysis of the distribution of
      these unigenes among the libraries led to the conclusion that the enrichment
      methods were effective in reducing the most abundant unigenes and to the
      observation that the most diverse libraries were from tissues exposed to
      environmental stresses including heat, drought, salinity, or low temperature.

PMID- 15514039
TI  - Chromosome bin map of expressed sequence tags in homoeologous group 1 of
      hexaploid wheat and homoeology with rice and Arabidopsis.
AB  - A total of 944 expressed sequence tags (ESTs) generated 2212 EST loci mapped to
      homoeologous group 1 chromosomes in hexaploid wheat (Triticum aestivum L.). EST
      deletion maps and the consensus map of group 1 chromosomes were constructed to
      show EST distribution. EST loci were unevenly distributed among chromosomes 1A,
      1B, and 1D with 660, 826, and 726, respectively. The number of EST loci was
      greater on the long arms than on the short arms for all three chromosomes. The
      distribution of ESTs along chromosome arms was nonrandom with EST clusters
      occurring in the distal regions of short arms and middle regions of long arms.
      Duplications of group 1 ESTs in other homoeologous groups occurred at a rate of
      35.5%. Seventy-five percent of wheat chromosome 1 ESTs had significant matches
      with rice sequences (E < or = e(-10)), where large regions of conservation
      occurred between wheat consensus chromosome 1 and rice chromosome 5 and between
      the proximal portion of the long arm of wheat consensus chromosome 1 and rice
      chromosome 10. Only 9.5% of group 1 ESTs showed significant matches to
      Arabidopsis genome sequences. The results presented are useful for gene mapping
      and evolutionary and comparative genomics of grasses.

PMID- 15514040
TI  - A 2600-locus chromosome bin map of wheat homoeologous group 2 reveals
      interstitial gene-rich islands and colinearity with rice.
AB  - The complex hexaploid wheat genome offers many challenges for genomics research.
      Expressed sequence tags facilitate the analysis of gene-coding regions and
      provide a rich source of molecular markers for mapping and comparison with model
      organisms. The objectives of this study were to construct a high-density EST
      chromosome bin map of wheat homoeologous group 2 chromosomes to determine the
      distribution of ESTs, construct a consensus map of group 2 ESTs, investigate
      synteny, examine patterns of duplication, and assess the colinearity with rice of
      ESTs assigned to the group 2 consensus bin map. A total of 2600 loci generated
      from 1110 ESTs were mapped to group 2 chromosomes by Southern hybridization onto
      wheat aneuploid chromosome and deletion stocks. A consensus map was constructed
      of 552 ESTs mapping to more than one group 2 chromosome. Regions of high gene
      density in distal bins and low gene density in proximal bins were found. Two
      interstitial gene-rich islands flanked by relatively gene-poor regions on both
      the short and long arms and having good synteny with rice were discovered. The
      map locations of two ESTs indicated the possible presence of a small pericentric
      inversion on chromosome 2B. Wheat chromosome group 2 was shown to share syntenous
      blocks with rice chromosomes 4 and 7.

PMID- 15514041
TI  - Group 3 chromosome bin maps of wheat and their relationship to rice chromosome 1.
AB  - The focus of this study was to analyze the content, distribution, and comparative
      genome relationships of 996 chromosome bin-mapped expressed sequence tags (ESTs)
      accounting for 2266 restriction fragments (loci) on the homoeologous group 3
      chromosomes of hexaploid wheat (Triticum aestivum L.). Of these loci, 634, 884,
      and 748 were mapped on chromosomes 3A, 3B, and 3D, respectively. The individual
      chromosome bin maps revealed bins with a high density of mapped ESTs in the
      distal region and bins of low density in the proximal region of the chromosome
      arms, with the exception of 3DS and 3DL. These distributions were more localized
      on the higher-resolution group 3 consensus map with intermediate regions of high
      mapped-EST density on both chromosome arms. Gene ontology (GO) classification of
      mapped ESTs was not significantly different for homoeologous group 3 chromosomes
      compared to the other groups. A combined analysis of the individual bin maps
      using 537 of the mapped ESTs revealed rearrangements between the group 3
      chromosomes. Approximately 232 (44%) of the consensus mapped ESTs matched
      sequences on rice chromosome 1 and revealed large- and small-scale differences in
      gene order. Of the group 3 mapped EST unigenes approximately 21 and 32% matched
      the Arabidopsis coding regions and proteins, respectively, but no chromosome
      level gene order conservation was detected.

PMID- 15514042
TI  - Analysis of expressed sequence tag loci on wheat chromosome group 4.
AB  - A total of 1918 loci, detected by the hybridization of 938 expressed sequence tag
      unigenes (ESTs) from 26 Triticeae cDNA libraries, were mapped to wheat (Triticum
      aestivum L.) homoeologous group 4 chromosomes using a set of deletion,
      ditelosomic, and nulli-tetrasomic lines. The 1918 EST loci were not distributed
      uniformly among the three group 4 chromosomes; 41, 28, and 31% mapped to
      chromosomes 4A, 4B, and 4D, respectively. This pattern is in contrast to the
      cumulative results of EST mapping in all homoeologous groups, as reported
      elsewhere, that found the highest proportion of loci mapped to the B genome.
      Sixty-five percent of these 1918 loci mapped to the long arms of homoeologous
      group 4 chromosomes, while 35% mapped to the short arms. The distal regions of
      chromosome arms showed higher numbers of loci than the proximal regions, with the
      exception of 4DL. This study confirmed the complex structure of chromosome 4A
      that contains two reciprocal translocations and two inversions, previously
      identified. An additional inversion in the centromeric region of 4A was revealed.
      A consensus map for homoeologous group 4 was developed from 119 ESTs unique to
      group 4. Forty-nine percent of these ESTs were found to be homoeologous to
      sequences on rice chromosome 3, 12% had matches with sequences on other rice
      chromosomes, and 39% had no matches with rice sequences at all. Limited homology
      (only 26 of the 119 consensus ESTs) was found between wheat ESTs on homoeologous
      group 4 and the Arabidopsis genome. Forty-two percent of the homoeologous group 4
      ESTs could be classified into functional categories on the basis of blastX
      searches against all protein databases.

PMID- 15514043
TI  - A 2500-locus bin map of wheat homoeologous group 5 provides insights on gene
      distribution and colinearity with rice.
AB  - We constructed high-density deletion bin maps of wheat chromosomes 5A, 5B, and
      5D, including 2338 loci mapped with 1052 EST probes and 217 previously mapped
      loci (total 2555 loci). This information was combined to construct a consensus
      chromosome bin map of group 5 including 24 bins. A relatively higher number of
      loci were mapped on chromosome 5B (38%) compared to 5A (34%) and 5D (28%).
      Differences in the levels of polymorphism among the three chromosomes were
      partially responsible for these differences. A higher number of duplicated loci
      was found on chromosome 5B (42%). Three times more loci were mapped on the long
      arms than on the short arms, and a significantly higher number of probes, loci,
      and duplicated loci were mapped on the distal halves than on the proximal halves
      of the chromosome arms. Good overall colinearity was observed among the three
      homoeologous group 5 chromosomes, except for the previously known 5AL/4AL
      translocation and a putative small pericentric inversion in chromosome 5A.
      Statistically significant colinearity was observed between low-copy-number ESTs
      from wheat homoeologous group 5 and rice chromosomes 12 (88 ESTs), 9 (72 ESTs),
      and 3 (84 ESTs).

PMID- 15514044
TI  - Deletion mapping of homoeologous group 6-specific wheat expressed sequence tags.
AB  - To localize wheat (Triticum aestivum L.) ESTs on chromosomes, 882 homoeologous
      group 6-specific ESTs were identified by physically mapping 7965 singletons from
      37 cDNA libraries on 146 chromosome, arm, and sub-arm aneuploid and deletion
      stocks. The 882 ESTs were physically mapped to 25 regions (bins) flanked by 23
      deletion breakpoints. Of the 5154 restriction fragments detected by 882 ESTs,
      2043 (loci) were localized to group 6 chromosomes and 806 were mapped on other
      chromosome groups. The number of loci mapped was greatest on chromosome 6B and
      least on 6D. The 264 ESTs that detected orthologous loci on all three homoeologs
      using one restriction enzyme were used to construct a consensus physical map. The
      physical distribution of ESTs was uneven on chromosomes with a tendency toward
      higher densities in the distal halves of chromosome arms. About 43% of the wheat
      group 6 ESTs identified rice homologs upon comparisons of genome sequences. Fifty
      eight percent of these ESTs were present on rice chromosome 2 and the remaining
      were on other rice chromosomes. Even within the group 6 bins, rice chromosomal
      blocks identified by 1-6 wheat ESTs were homologous to up to 11 rice chromosomes.
      These rice-block contigs were used to resolve the order of wheat ESTs within each
      bin.

PMID- 15514045
TI  - A chromosome bin map of 2148 expressed sequence tag loci of wheat homoeologous
      group 7.
AB  - The objectives of this study were to develop a high-density chromosome bin map of
      homoeologous group 7 in hexaploid wheat (Triticum aestivum L.), to identify gene
      distribution in these chromosomes, and to perform comparative studies of wheat
      with rice and barley. We mapped 2148 loci from 919 EST clones onto group 7
      chromosomes of wheat. In the majority of cases the numbers of loci were
      significantly lower in the centromeric regions and tended to increase in the
      distal regions. The level of duplicated loci in this group was 24% with most of
      these loci being localized toward the distal regions. One hundred nineteen EST
      probes that hybridized to three fragments and mapped to the three group 7
      chromosomes were designated landmark probes and were used to construct a
      consensus homoeologous group 7 map. An additional 49 probes that mapped to 7AS,
      7DS, and the ancestral translocated segment involving 7BS also were designated
      landmarks. Landmark probe orders and comparative maps of wheat, rice, and barley
      were produced on the basis of corresponding rice BAC/PAC and genetic markers that
      mapped on chromosomes 6 and 8 of rice. Identification of landmark ESTs and
      development of consensus maps may provide a framework of conserved coding regions
      predating the evolution of wheat genomes.

PMID- 15514046
TI  - A chromosome bin map of 16,000 expressed sequence tag loci and distribution of
      genes among the three genomes of polyploid wheat.
AB  - Because of the huge size of the common wheat (Triticum aestivum L., 2n = 6x = 42,
      AABBDD) genome of 17,300 Mb, sequencing and mapping of the expressed portion is a
      logical first step for gene discovery. Here we report mapping of 7104 expressed
      sequence tag (EST) unigenes by Southern hybridization into a chromosome bin map
      using a set of wheat aneuploids and deletion stocks. Each EST detected a mean of
      4.8 restriction fragments and 2.8 loci. More loci were mapped in the B genome
      (5774) than in the A (5173) or D (5146) genomes. The EST density was
      significantly higher for the D genome than for the A or B. In general, EST
      density increased relative to the physical distance from the centromere. The
      majority of EST-dense regions are in the distal parts of chromosomes. Most of the
      agronomically important genes are located in EST-dense regions. The chromosome
      bin map of ESTs is a unique resource for SNP analysis, comparative mapping,
      structural and functional analysis, and polyploid evolution, as well as providing
      a framework for constructing a sequence-ready, BAC-contig map of the wheat
      genome.

PMID- 15514047
TI  - ospC diversity in Borrelia burgdorferi: different hosts are different niches.
AB  - The outer surface protein C (ospC) locus of the Lyme disease bacterium, Borrelia
      burgdorferi, is at least an order of magnitude more variable than other genes in
      the species. This variation is classified into 22 ospC major groups, 15 of which
      are found in the northeastern United States. The frequency distributions of ospC
      within populations suggest that this locus is under balancing selection. In
      multiple-niche polymorphism, a type of balancing selection, diversity within a
      population can be maintained when the environment is heterogeneous and no one
      genotype has the highest fitness in all environments. Genetically different
      individuals within vertebrate species and different vertebrate species constitute
      diverse environments for B. burgdorferi. We examined four important host species
      of B. burgdorferi and found that the strains that infected each species had
      different sets of ospC major groups. We found no variation among conspecific
      hosts in the ospC major groups of their infecting strains. These results suggest
      multiple niches create balancing selection at the ospC locus.

PMID- 15514048
TI  - Enolase and glycolytic flux play a role in the regulation of the glucose permease
      gene RAG1 of Kluyveromyces lactis.
AB  - We isolated a mutant, rag17, which is impaired in glucose induction of expression
      of the major glucose transporter gene RAG1. The RAG17 gene encodes a protein 87%
      identical to S. cerevisiae enolases (Eno1 and Eno2). The Kleno null mutant showed
      no detectable enolase enzymatic activity and has severe growth defects on glucose
      and gluconeogenic carbon sources, indicating that K. lactis has a single enolase
      gene. In addition to RAG1, the transcription of several glycolytic genes was also
      strongly reduced in the DeltaKleno mutant. Moreover, the defect in RAG1
      expression was observed in other mutants of the glycolytic pathway (hexokinase
      and phosphoglycerate kinase). Therefore, it seems that the enolase and a
      functional glycolytic flux are necessary for induction of expression of the Rag1
      glucose permease in K. lactis.

PMID- 15514049
TI  - Lrg1p Is a Rho1 GTPase-activating protein required for efficient cell fusion in
      yeast.
AB  - To identify additional cell fusion genes in Saccharomyces cerevisiae, we
      performed a high-copy suppressor screen of fus2Delta. Higher dosage of three
      genes, BEM1, LRG1, and FUS1, partially suppressed the fus2Delta cell fusion
      defect. BEM1 and FUS1 were high-copy suppressors of many cell-fusion-defective
      mutations, whereas LRG1 suppressed only fus2Delta and rvs161Delta. Lrg1p contains
      a Rho-GAP homologous region. Complete deletion of LRG1, as well as deletion of
      the Rho-GAP coding region, caused decreased rates of cell fusion and diploid
      formation comparable to that of fus2Delta. Furthermore, lrg1Delta caused a more
      severe mating defect in combination with other cell fusion mutations. Consistent
      with an involvement in cell fusion, Lrg1p localized to the tip of the mating
      projection. Lrg1p-GAP domain strongly and specifically stimulated the GTPase
      activity of Rho1p, a regulator of beta(1-3)-glucan synthase in vitro. beta(1-3)
      glucan deposition was increased in lrg1Delta strains and mislocalized to the tip
      of the mating projection in fus2Delta strains. High-copy LRG1 suppressed the
      mislocalization of beta(1-3) glucan in fus2Delta strains. We conclude that Lrg1p
      is a Rho1p-GAP involved in cell fusion and speculate that it acts to locally
      inhibit cell wall synthesis to aid in the close apposition of the plasma
      membranes of mating cells.

PMID- 15514050
TI  - Mutations in SIN4 and RGR1 cause constitutive expression of MAL structural genes
      in Saccharomyces cerevisiae.
AB  - Transcription of the Saccharomyces MAL structural genes is induced 40-fold by
      maltose and requires the MAL-activator and maltose permease. To identify
      additional players involved in regulating MAL gene expression, we carried out a
      genetic selection for MAL constitutive mutants. Strain CMY4000 containing MAL1
      and integrated copies of MAL61promoter-HIS3 and MAL61promoter-lacZ reporter genes
      was used to select constitutive mutants. The 29 recessive mutants fall into at
      least three complementation groups. Group 1 and group 2 mutants exhibit
      pleiotropic phenotypes and represent alleles of Mediator component genes RGR1 and
      SIN4, respectively. The rgr1 and sin4 constitutive phenotype does not require
      either the MAL-activator or maltose permease, indicating that Mediator represses
      MAL basal expression. Further genetic analysis demonstrates that RGR1 and SIN4
      work in a common pathway and each component of the Mediator Sin4 module plays a
      distinct role in regulating MAL gene expression. Additionally, the Swi/Snf
      chromatin-remodeling complex is required for full induction, suggesting a role
      for chromatin remodeling in the regulation of MAL gene expression. A sin4Delta
      mutation is unable to suppress the defects in MAL gene expression resulting from
      loss of the Swi/Snf complex component Snf2p. The role of the Mediator in MAL gene
      regulation is discussed.

PMID- 15514052
TI  - Meiotic chromosome synapsis in yeast can occur without spo11-induced DNA double
      strand breaks.
AB  - Proper chromosome segregation and formation of viable gametes depend on synapsis
      and recombination between homologous chromosomes during meiosis. Previous reports
      have shown that the synaptic structures, the synaptonemal complexes (SCs), do not
      occur in yeast cells with the SPO11 gene removed. The Spo11 enzyme makes double
      strand breaks (DSBs) in the DNA and thereby initiates recombination. The view has
      thus developed that synapsis in yeast strictly depends on the initiation of
      recombination. Synapsis in some other species (Drosophila melanogaster and
      Caenorhabditis elegans) is independent of recombination events, and SCs are found
      in spo11 mutants. This difference between species led us to reexamine spo11
      deletion mutants of yeast. Using antibodies against Zip1, a SC component, we
      found that a small fraction (1%) of the spo11 null mutant cells can indeed form
      wild-type-like SCs. We further looked for synapsis in a spo11 mutant strain that
      accumulates pachytene cells (spo11Delta ndt80Delta), and found that the frequency
      of cells with apparently complete SC formation was 10%. Other phenotypic
      criteria, such as spore viability and homologous chromosome juxtaposition
      measured by FISH labeling of chromosomal markers, agree with several previous
      reports of the spo11 mutant. Our results demonstrate that although the Spo11
      induced DSBs obviously promote synapsis in yeast, the presence of Spo11 is not an
      absolute requirement for synapsis.

PMID- 15514051
TI  - A functional analysis reveals dependence on the anaphase-promoting complex for
      prolonged life span in yeast.
AB  - Defects in anaphase-promoting complex (APC) activity, which regulates mitotic
      progression and chromatin assembly, results in genomic instability, a hallmark of
      premature aging and cancer. We investigated whether APC-dependent genomic
      stability affects aging and life span in yeast. Utilizing replicative and
      chronological aging assays, the APC was shown to promote longevity. Multicopy
      expression of genes encoding Snf1p (MIG1) and PKA (PDE2) aging-pathway components
      suppressed apc5CA phenotypes, suggesting their involvement in APC-dependent
      longevity. While it is known that PKA inhibits APC activity and reduces life
      span, a link between the Snf1p-inhibited Mig1p transcriptional modulator and the
      APC is novel. Our mutant analysis supports a model in which Snf1p promotes
      extended life span by inhibiting the negative influence of Mig1p on the APC.
      Consistent with this, we found that increased MIG1 expression reduced replicative
      life span, whereas mig1Delta mutations suppressed the apc5CA chronological aging
      defect. Furthermore, Mig1p and Mig2p activate APC gene transcription,
      particularly on glycerol, and mig2Delta, but not mig1Delta, confers a prolonged
      replicative life span in both APC5 and acp5CA cells. However, glucose repression
      of APC genes was Mig1p and Mig2p independent, indicating the presence of an
      uncharacterized factor. Therefore, we propose that APC-dependent genomic
      stability is linked to prolonged longevity by the antagonistic regulation of the
      PKA and Snf1p pathways.

PMID- 15514053
TI  - Connection of propionyl-CoA metabolism to polyketide biosynthesis in Aspergillus
      nidulans.
AB  - Propionyl-CoA is an intermediate metabolite produced through a variety of
      pathways including thioesterification of propionate and catabolism of odd chain
      fatty acids and select amino acids. Previously, we found that disruption of the
      methylcitrate synthase gene, mcsA, which blocks propionyl-CoA utilization, as
      well as growth on propionate impaired production of several polyketides-molecules
      typically derived from acetyl-CoA and malonyl-CoA-including sterigmatocystin
      (ST), a potent carcinogen, and the conidiospore pigment. Here we describe three
      lines of evidence that demonstrate that excessive propionyl-CoA levels in the
      cell can inhibit polyketide synthesis. First, inactivation of a putative
      propionyl-CoA synthase, PcsA, which converts propionate to propionyl-CoA,
      restored polyketide production and reduced cellular propionyl-CoA content in a
      DeltamcsA background. Second, inactivation of the acetyl-CoA synthase, FacA,
      which is also involved in propionate utilization, restored polyketide production
      in the DeltamcsA background. Third, fungal growth on several compounds (e.g.,
      heptadecanoic acid, isoleucine, and methionine) whose catabolism includes the
      formation of propionyl-CoA, were found to inhibit ST and conidiospore pigment
      production. These results demonstrate that excessive propionyl-CoA levels in the
      cell can inhibit polyketide synthesis.

PMID- 15514055
TI  - Role of a nonselective de novo DNA methyltransferase in maternal inheritance of
      chloroplast genes in the green alga, Chlamydomonas reinhardtii.
AB  - In the green alga, Chlamydomonas, chloroplast DNA is maternally transmitted to
      the offspring. We previously hypothesized that the underlying molecular mechanism
      involves specific methylation of maternal gamete DNA before mating, protecting
      against degradation. To obtain direct evidence for this, we focused on a DNA
      methyltransferase, DMT1, which was previously shown to be localized in
      chloroplasts. The full-length DMT1 protein with a molecular mass of 150 kD was
      expressed in insect cells, and its catalytic activity was determined. In vitro
      assays using synthetic DNA indicated methylation of all cytosine residues, with
      no clear selectivity in terms of the neighboring nucleotides. Subsequently,
      transgenic paternal cells constitutively expressing DMT1 were constructed and
      direct methylation mapping assays of their DNA showed a clear nonselective
      methylation of chloroplast DNA. When transgenic paternal cells were crossed with
      wild-type maternal cells, the frequency of biparental and paternal offspring of
      chloroplasts increased up to 23% while between wild-type strains it was
      approximately 3%. The results indicate that DMT1 is a novel type of DNA
      methyltransferase with a nonselective cytosine methylation activity, and that
      chloroplast DNA methylation by DMT1 is one of factors influencing maternal
      inheritance of chloroplast genes.

PMID- 15514054
TI  - Genetic dissection of nutritional copper signaling in chlamydomonas distinguishes
      regulatory and target genes.
AB  - A genetic screen for Chlamydomonas reinhardtii mutants with copper-dependent
      growth or nonphotosynthetic phenotypes revealed three loci, COPPER RESPONSE
      REGULATOR 1 (CRR1), COPPER RESPONSE DEFECT 1 (CRD1), and COPPER RESPONSE DEFECT 2
      (CRD2), distinguished as regulatory or target genes on the basis of phenotype.
      CRR1 was shown previously to be required for transcriptional activation of target
      genes like CYC6, CPX1, and CRD1, encoding, respectively, cytochrome c(6) (which
      is a heme-containing substitute for copper-containing plastocyanin),
      coproporphyrinogen III oxidase, and Mg-protoporphyrin IX monomethylester cyclase.
      We show here that CRR1 is required also for normal accumulation of copper
      proteins like plastocyanin and ferroxidase in copper-replete medium and for
      apoplastocyanin degradation in copper-deficient medium, indicating that a single
      pathway controls nutritional copper homeostasis at multiple levels. CRR1 is
      linked to the SUPPRESSOR OF PCY1-AC208 13 (SOP13) locus, which corresponds to a
      gain-of-function mutation resulting in copper-independent expression of CYC6.
      CRR1 is required also for hypoxic growth, pointing to a physiologically
      meaningful regulatory connection between copper deficiency and hypoxia. The
      growth phenotype of crr1 strains results primarily from secondary iron deficiency
      owing to reduced ferroxidase abundance, suggesting a role for CRR1 in copper
      distribution to a multicopper ferroxidase involved in iron assimilation.
      Mutations at the CRD2 locus also result in copper-conditional iron deficiency,
      which is consistent with a function for CRD2 in a pathway for copper delivery to
      the ferroxidase. Taken together, the observations argue for a specialized copper
      deficiency adaptation for iron uptake in Chlamydomonas.

PMID- 15514056
TI  - Caenorhabditis elegans atx-2 promotes germline proliferation and the oocyte fate.
AB  - In the Caenorhabditis elegans germline, proliferation is induced by Notch-type
      signaling. Entry of germ cells into meiosis is triggered by activity of the GLD-1
      and GLD-2 pathways, which function redundantly to promote meiosis and/or inhibit
      proliferation. Activation of the germline Notch-type receptor, GLP-1, ultimately
      inhibits the activities of the GLD-1 and GLD-2 pathways. We previously identified
      several ego (enhancer of glp-1) genes that promote germline proliferation and
      interact genetically with the GLP-1 signaling pathway. Here, we show that atx-2
      is an ego gene. Our data suggest that ATX-2 is not a positive regulator of the
      GLP-1 signaling pathway and GLP-1 signaling is not the sole positive regulator of
      ATX-2 activity. Moreover, our data indicate that GLP-1 must have an additional
      function, which may be to repress activity of a third meiotic entry pathway that
      would work in parallel with the GLD-1 and GLD-2 pathways. In addition to its role
      in proliferation, ATX-2 acts downstream of FOG-2 to promote the female germline
      fate.

PMID- 15514057
TI  - Resistance to volatile anesthetics by mutations enhancing excitatory
      neurotransmitter release in Caenorhabditis elegans.
AB  - The molecular mechanisms whereby volatile general anesthetics (VAs) disrupt
      behavior remain undefined. In Caenorhabditis elegans mutations in the gene unc
      64, which encodes the presynaptic protein syntaxin 1A, produce large allele
      specific differences in VA sensitivity. UNC-64 syntaxin normally functions to
      mediate fusion of neurotransmitter vesicles with the presynaptic membrane. The
      precise role of syntaxin in the VA mechanism is as yet unclear, but a variety of
      results suggests that a protein interacting with syntaxin to regulate
      neurotransmitter release is essential for VA action in C. elegans. To identify
      additional proteins that function with syntaxin to control neurotransmitter
      release and VA action, we screened for suppressors of the phenotypes produced by
      unc-64 reduction of function. Loss-of-function mutations in slo-1, which encodes
      a Ca(2+)-activated K+ channel, and in unc-43, which encodes CaM-kinase II, and a
      gain-of-function mutation in egl-30, which encodes Gqalpha, were isolated as
      syntaxin suppressors. The slo-1 and egl-30 mutations conferred resistance to VAs,
      but unc-43 mutations did not. The effects of slo-1 and egl-30 on VA sensitivity
      can be explained by their actions upstream or parallel to syntaxin to increase
      the level of excitatory neurotransmitter release. These results strengthen the
      link between transmitter release and VA action.

PMID- 15514058
TI  - Thiamine pyrophosphate biosynthesis and transport in the nematode Caenorhabditis
      elegans.
AB  - Thiamine (vitamin B1) is required in the diet of animals, and thiamine deficiency
      leads to diseases such as beri-beri and the Wernicke-Korsakoff syndrome. Dietary
      thiamine (vitamin B1) consists mainly of thiamine pyrophosphate (TPP), which is
      transformed into thiamine by gastrointestinal phosphatases before absorption. It
      is believed that TPP itself cannot be transported across plasma membranes in
      significant amounts. We have identified a partial loss-of-function mutation in
      the Caenorhabditis elegans gene (tpk-1) that encodes thiamine pyrophosphokinase,
      which forms TPP from thiamine at the expense of ATP inside cells. The mutation
      slows physiological rhythms and the phenotype it produces can be rescued by TPP
      but not thiamine supplementation. tpk-1 functions cell nonautonomously, as the
      expression of wild-type tpk-1 in one tissue can rescue the function of other
      tissues that express only mutant tpk-1. These observations indicate that, in
      contrast to expectation from previous evidence, TPP can be transported across
      cell membranes. We also find that thiamine supplementation partially rescues the
      phenotype of partial loss-of-function mutants of the Na/K ATPase, providing
      genetic evidence that thiamine absorption, and/or redistribution from the
      absorbing cells, requires the full activity of this enzyme.

PMID- 15514059
TI  - Drosophila damaged DNA-binding protein 1 is an essential factor for development.
AB  - The damaged DNA-binding protein (DDB) complex, thought to recognize (6-4)
      photoproducts and other lesions in DNA, has been implicated to have a role in
      global genomic nucleotide excision repair (NER) and E2F-1-mediated transcription.
      The complex consists of a heterodimer of p127 (DDB1) and p48 (DDB2), the latter
      also being known as XPE. We reported previously that in Drosophila expression of
      the DDB1 (D-DDB1) gene is controlled by the DRE/DREF system, and external injury
      to DNA is not essential for D-DDB1 function. In the present study of the function
      of D-DDB1 in a multicellular system, we prepared transgenic flies, which were
      knocked down for the D-DDB1 gene due to RNA interference (RNAi), and performed
      immunocytochemistry to ascertain the distribution of D-DDB1 in the eye imaginal
      disc. It was found to be abundant in the anterior of the morphogenetic furrow
      (MF). Whole-body overexpression of dsRNA of D-DDB1 in Drosophila using a GAL4-UAS
      targeted expression system induced melanotic tumors and caused complete
      lethality. When limited to the eye imaginal disc, a severe rough eye phenotype
      resulted. Correspondingly, all of the D-DDB1 gene knocked-out flies also died. D
      DDB1 therefore appears to be an essential development-associated factor in a
      multicellular organism.

PMID- 15514060
TI  - Cyclin D does not provide essential Cdk4-independent functions in Drosophila.
AB  - The three mammalian D-type cyclins are thought to promote progression through the
      G1 phase of the cell cycle as regulatory subunits of cyclin-dependent kinase 4
      and 6. In addition, they have been proposed to control the activity of various
      transcription factors without a partner kinase. Here we describe phenotypic
      consequences of null mutations in Cyclin D, the single D-type cyclin gene in
      Drosophila. As previously observed with null mutations in the single Drosophila
      Cdk4 gene, these mutations do not primarily affect progression through the G1
      phase. Moreover, the apparently indistinguishable phenotypes of double (CycD and
      Cdk4) and single mutants (CycD or Cdk4) argue against major independent functions
      of Cyclin D and Cdk4. The reduced cellular and organismal growth rates observed
      in both mutants indicate that Cyclin D-Cdk4 acts as a growth driver.

PMID- 15514061
TI  - CREB binding protein functions during successive stages of eye development in
      Drosophila.
AB  - During the development of the compound eye of Drosophila several signaling
      pathways exert both positive and inhibitory influences upon an array of nuclear
      transcription factors to produce a near-perfect lattice of unit eyes or
      ommatidia. Individual cells within the eye are exposed to many extracellular
      signals, express multiple surface receptors, and make use of a large complement
      of cell-subtype-specific DNA-binding transcription factors. Despite this enormous
      complexity, each cell will make the correct developmental choice and adopt the
      appropriate cell fate. How this process is managed remains a poorly understood
      paradigm. Members of the CREB binding protein (CBP)/p300 family have been shown
      to influence development by (1) acting as bridging molecules between the basal
      transcriptional machinery and specific DNA-binding transcription factors, (2)
      physically interacting with terminal members of signaling cascades, (3) acting as
      transcriptional coactivators of downstream target genes, and (4) playing a key
      role in chromatin remodeling. In a screen for new genes involved in eye
      development we have identified the Drosophila homolog of CBP as a key player in
      both eye specification and cell fate determination. We have used a variety of
      approaches to define the role of CBP in eye development on a cell-by-cell basis.

PMID- 15514062
TI  - Mutations in the Drosophila condensin subunit dCAP-G: defining the role of
      condensin for chromosome condensation in mitosis and gene expression in
      interphase.
AB  - Chromosomes are dynamic structures that are reorganized during the cell cycle to
      optimize them for distinct functions. SMC and non-SMC condensin proteins
      associate into complexes that have been implicated in the process of chromosome
      condensation. The roles of the individual non-SMC subunits of the complex are
      poorly understood, and mutations in the CAP-G subunit have not been described in
      metazoans. Here we elucidate a role for dCAP-G in chromosome condensation and
      cohesion in Drosophila. We illustrate the requirement of dCAP-G for condensation
      during prophase and prometaphase; however, we find that alternate mechanisms
      ensure that replicated chromosomes are condensed prior to metaphase. In contrast,
      dCAP-G is essential for chromosome condensation in metaphase of single,
      unreplicated sister chromatids, suggesting that there is an interplay between
      replicated chromatids and the condensin complex. In the dcap-g mutants, defects
      in sister-chromatid separation are also observed. Chromatid arms fail to resolve
      in prophase and are unable to separate at anaphase, whereas sister centromeres
      show aberrant separation in metaphase and successfully move to spindle poles at
      anaphase. We also identified a role for dCAP-G during interphase in regulating
      heterochromatic gene expression.

PMID- 15514063
TI  - The gene Sex-lethal of the Sciaridae family (order Diptera, suborder Nematocera)
      and its phylogeny in dipteran insects.
AB  - This article reports the cloning and characterization of the gene homologous to
      Sex-lethal (Sxl) of Drosophila melanogaster from Sciara coprophila, Rhynchosciara
      americana, and Trichosia pubescens. This gene plays the key role in controlling
      sex determination and dosage compensation in D. melanogaster. The Sxl gene of the
      three species studied produces a single transcript encoding a single protein in
      both males and females. Comparison of the Sxl proteins of these Nematocera
      insects with those of the Brachycera showed their two RNA-binding domains (RBD)
      to be highly conserved, whereas significant variation was observed in both the N-
      and C-terminal domains. The great majority of nucleotide changes in the RBDs were
      synonymous, indicating that purifying selection is acting on them. In both sexes
      of the three Nematocera insects, the Sxl protein colocalized with transcription
      active regions dependent on RNA polymerase II but not on RNA polymerase I.
      Together, these results indicate that Sxl does not appear to play a
      discriminatory role in the control of sex determination and dosage compensation
      in nematocerans. Thus, in the phylogenetic lineage that gave rise to the
      drosophilids, evolution coopted for the Sxl gene, modified it, and converted it
      into the key gene controlling sex determination and dosage compensation. At the
      same time, however, certain properties of the recruited ancestral Sxl gene were
      beneficial, and these are maintained in the evolved Sxl gene, allowing it to
      exert its sex-determining and dose compensation functions in Drosophila.

PMID- 15514064
TI  - Single-locus latitudinal clines and their relationship to temperate adaptation in
      metabolic genes and derived alleles in Drosophila melanogaster.
AB  - We report a study in Drosophila melanogaster of latitudinal clines for 23 SNPs
      embedded in 13 genes (Pgi, Gapdh1, UGPase, Pglym78, Pglym87, Eno, Men, Gdh, Sod,
      Pgk, Mdh1, TreS, Treh) representing various metabolic enzymes. Our samples are
      from 10 populations spanning latitude from southern Florida to northern Vermont.
      Three new clines with latitude were detected. These are the amino acid
      polymorphisms in the NAD-dependent glutamate dehydrogenase (Gdh) and trehalase
      (Treh) genes, and a silent site polymorphism in the UDP-glucose pyrophosphorylase
      gene (UGPase). The result, when combined with the overall incidence and pattern
      of reports for six other genes (Adh, Gpdh, Pgm, G6pd, 6Pgd, Hex-C), presents a
      picture of latitudinal clines in metabolic genes prevalent around the branch
      point of competing pathways. For six of the seven amino acid polymorphisms
      showing significant latitudinal clines in North America, the derived allele is
      the one increasing with latitude, suggesting temperate adaptation. This is
      consistent with a model of an Afrotropical ancestral species adapting to
      temperate climates through selection favoring new mutations.

PMID- 15514065
TI  - Natural genetic variation caused by transposable elements in humans.
AB  - Transposons and transposon-like repetitive elements collectively occupy 44% of
      the human genome sequence. In an effort to measure the levels of genetic
      variation that are caused by human transposons, we have developed a new method to
      broadly detect transposon insertion polymorphisms of all kinds in humans. We
      began by identifying 606,093 insertion and deletion (indel) polymorphisms in the
      genomes of diverse humans. We then screened these polymorphisms to detect indels
      that were caused by de novo transposon insertions. Our method was highly
      efficient and led to the identification of 605 nonredundant transposon insertion
      polymorphisms in 36 diverse humans. We estimate that this represents 25-35% of
      approximately 2075 common transposon polymorphisms in human populations. Because
      we identified all transposon insertion polymorphisms with a single method, we
      could evaluate the relative levels of variation that were caused by each
      transposon class. The average human in our study was estimated to harbor 1283 Alu
      insertion polymorphisms, 180 L1 polymorphisms, 56 SVA polymorphisms, and 17
      polymorphisms related to other forms of mobilized DNA. Overall, our study
      provides significant steps toward (i) measuring the genetic variation that is
      caused by transposon insertions in humans and (ii) identifying the transposon
      copies that produce this variation.

PMID- 15514066
TI  - Mutation rate and predicted phenotypic target sizes in ethylnitrosourea-treated
      mice.
AB  - Chemical mutagenesis of the mouse is ongoing in several centers around the world,
      with varying estimates of mutation rate and number of sites mutable to phenotype.
      To address these questions, we sequenced approximately 9.6 Mb of DNA from G1
      progeny of ethylnitrosourea-treated mice in a large, broad-spectrum screen. We
      identified 10 mutations at eight unique sites, including six nonsynonymous coding
      substitutions. This calibrates the nucleotide mutation rate for two mutagenesis
      centers, implies significance criteria for positional cloning efforts, and
      provides working estimates of effective genetic target sizes for selected
      phenotypes.

PMID- 15514067
TI  - Epigenetic control of CACTA transposon mobility in Arabidopsis thaliana.
AB  - Epigenetic mutation, heritable developmental variation not based on a change in
      nucleotide sequence, is widely reported in plants. However, the developmental and
      evolutionary significance of such mutations remains enigmatic. On the basis of
      our studies of the endogenous Arabidopsis transposon CACTA, we propose that the
      inheritance of epigenetic gene silencing over generations can function as a
      transgenerational genome defense mechanism against deleterious movement of
      transposons. We previously reported that silent CACTA1 is mobilized by the DNA
      hypomethylation mutation ddm1 (decrease in DNA methylation). In this study, we
      report that CACTA activated by the ddm1 mutation remains mobile in the presence
      of the wild-type DDM1 gene, suggesting that de novo silencing is not efficient
      for the defense of the genome against CACTA movement. The defense depends on
      maintenance of transposon silencing over generations. In addition, we show that
      the activated CACTA1 element transposes throughout the genome in DDM1 plants, as
      reported previously for ddm1 backgrounds. Furthermore, the CACTA1 element
      integrated into both the ddm1-derived and the DDM1-derived chromosomal regions in
      the DDM1 wild-type plants, demonstrating that this class of transposons does not
      exhibit targeted integration into heterochromatin, despite its accumulation in
      the pericentromeric regions in natural populations. The possible contribution of
      natural selection as a mechanism for the accumulation of transposons and
      evolution of heterochromatin is discussed.

PMID- 15514068
TI  - Arabidopsis hapless mutations define essential gametophytic functions.
AB  - In flowering plants, the egg develops within a haploid embryo sac (female
      gametophyte) that is encased within the pistil. The haploid pollen grain (male
      gametophyte) extends a pollen tube that carries two sperm cells within its
      cytoplasm to the embryo sac. This feat requires rapid, precisely guided, and
      highly polarized growth through, between, and on the surface of the cells of the
      stigma, style, and ovary. Pollen tube migration depends on a series of long-range
      signals from diploid female cells as well as a short-range attractant emitted by
      the embryo sac that guides the final stage of tube growth. We developed a genetic
      screen in Arabidopsis thaliana that tags mutant pollen with a cell-autonomous
      marker carried on an insertion element. We found 32 haploid-disrupting (hapless)
      mutations that define genes required for pollen grain development, pollen tube
      growth in the stigma and style, or pollen tube growth and guidance in the ovary.
      We also identified genomic DNA flanking the insertion element for eleven hap
      mutants and showed that hap1 disrupts AtMago, a gene whose ortholog is important
      for Drosophila cell polarity.

PMID- 15514069
TI  - Interval mapping of quantitative trait loci for resistance to late blight
      [Phytophthora infestans (Mont.) de Bary], height and maturity in a tetraploid
      population of potato (Solanum tuberosum subsp. tuberosum).
AB  - Interval mapping of quantitative trait loci (QTL) for resistance to late blight,
      height, and maturity was performed on a tetraploid full-sib family of potato
      comprising 227 clones from a cross between a susceptible parent, 12601ab1, and a
      resistant cultivar, Stirling, which were of similar height and main crop
      maturity. Thirty-eight AFLP primer combinations provided 585 informative markers,
      and 23 SSRs proved useful for identifying linkage groups (LGs). A simplex QTL
      allele was found on LGV of Stirling close to marker STM3179, which was associated
      with early maturity, short plants, and susceptibility to blight and explained
      54.7, 26.5, 26.3, and 17.5% of the variation for maturity, height, tuber blight,
      and foliage blight. When the residuals from the regressions of foliage and tuber
      blight on maturity were analyzed, there was no significant effect of a QTL on
      LGV, but a duplex QTL allele for resistance was found on LGIV of Stirling, which
      explained 30.7 and 13.6% of the variation for foliage and tuber blight on an
      additive model. Partial dominance for resistance explained even more of the
      variation, up to 37.2% for foliage blight. A major gene for blight resistance in
      Stirling was also mapped to LGXI.

PMID- 15514070
TI  - Allelic diversification at the C (OsC1) locus of wild and cultivated rice:
      nucleotide changes associated with phenotypes.
AB  - Divergent phenotypes are often detected in domesticated plants despite the
      existence of invariant phenotypes in their wild forms. One such example in rice
      is the occurrence of varying degrees of apiculus coloration due to anthocyanin
      pigmentation, which was previously reported to be caused by a series of alleles
      at the C locus. The present study reveals, on the basis of comparison of its
      maps, that the C gene appears to be the rice homolog (OsC1) of maize C1, which
      belongs to the group of R2R3-Myb factors. Two different types of deletions
      causing a frameshift were detected in the third exon, and both of the deleted
      nucleotides corresponded to the positions of putative base-contacting residues,
      suggesting that the Indica and Japonica types carry loss-of-function mutations
      with independent origins. In addition, replacement substitutions were frequently
      detected in OsC1 of strains carrying the previously defined C alleles. Molecular
      population analysis revealed that 17 haplotypes were found in 39 wild and
      cultivated rices, and the haplotypes of most cultivated forms could be classified
      into one of three distinct groups, with few shared haplotypes among taxa,
      including Indica and Japonica types. The genealogy of the OsC1 gene suggests that
      allelic diversification causing phenotypic change might have resulted from
      mutations in the coding region rather than from recombination between preexisting
      alleles. The McDonald and Kreitman test revealed that the changes in amino acids
      might be associated with selective forces acting on the lineage of group A whose
      haplotypes were carried by most Asian cultivated forms. The results regarding a
      significant implication for genetic diversity in landraces of rice are also
      discussed.

PMID- 15514071
TI  - Fixation probability favors increased fecundity over reduced generation time.
AB  - The cornerstone of population genetics is a probabilistic understanding of the
      ultimate fate--survival or extinction--of rare mutations. If a mutation is
      beneficial, it enables its carrier to reproduce faster than native wild-type
      individuals. In classic derivations and in the considerable body of research that
      has followed, "faster" has been defined mathematically to mean "able to produce
      more surviving offspring per generation." Many organisms, however, may increase
      their reproductive rate by producing the same number of offspring in a shorter
      generation time: a mutant bacterium, for example, may complete the cell cycle and
      produce two offspring more quickly than the wild type. We find that the ultimate
      fixation probability of a mutation conferring a shorter generation time differs
      from that of a mutation conferring more offspring by a factor of 2 ln(2)-nearly
      40%. This predicts a reduction in the overall substitution rate for any mutation
      that decreases the generation time: fixation probability is biased toward
      increased offspring number.

PMID- 15514072
TI  - Multiple quantitative trait loci mapping with cofactors and application of
      alternative variants of the false discovery rate in an enlarged granddaughter
      design.
AB  - The experimental power of a granddaughter design to detect quantitative trait
      loci (QTL) in dairy cattle is often limited by the availability of progeny-tested
      sires, by the ignoring of already identified QTL in the statistical analysis, and
      by the application of stringent experimentwise significance levels. This study
      describes an experiment that addressed these points. A large granddaughter design
      was set up that included sires from two countries (Germany and France), resulting
      in almost 2000 sires. The animals were genotyped for markers on nine different
      chromosomes. The QTL analysis was done for six traits separately using a
      multimarker regression that included putative QTL on other chromosomes as
      cofactors in the model. Different variants of the false discovery rate (FDR) were
      applied. Two of them accounted for the proportion of truly null hypotheses, which
      were estimated to be 0.28 and 0.3, respectively, and were therefore tailored to
      the experiment. A total of 25 QTL could be mapped when cofactors were included in
      the model-7 more than without cofactors. Controlling the FDR at 0.05 revealed 31
      QTL for the two FDR methods that accounted for the proportion of truly null
      hypotheses. The relatively high power of this study can be attributed to the size
      of the experiment, to the QTL analysis with cofactors, and to the application of
      an appropriate FDR.

PMID- 15514073
TI  - Effect of two- and three-locus linkage disequilibrium on the power to detect
      marker/phenotype associations.
AB  - There has been much recent interest in describing the patterns of linkage
      disequilibrium (LD) along a chromosome. Most empirical studies that have examined
      this issue have concentrated on LD between collections of pairs of markers and
      have not considered the joint effect of a group of markers beyond these pairwise
      connections. Here, we examine many different patterns of LD defined by both
      pairwise and joint multilocus LD terms. The LD patterns we considered were chosen
      in part by examining those seen in real data. We examine how changes in these
      patterns affect the power to detect association when performing single-marker and
      haplotype-based case-control tests, including a novel haplotype test based on
      contrasting LD between affected and unaffected individuals. Through our studies
      we find that differences in power between single-marker tests and haplotype-based
      tests in general do not appear to be large. Where moderate to high levels of
      multilocus LD exist, haplotype tests tend to be more powerful. Single-marker
      tests tend to prevail when pairwise LD is high. For moderate pairwise values and
      weak multilocus LD, either testing strategy may come out ahead, although it is
      also quite likely that neither has much power.

PMID- 15514074
TI  - Accuracy and power of statistical methods for detecting adaptive evolution in
      protein coding sequences and for identifying positively selected sites.
AB  - The parsimony method of Suzuki and Gojobori (1999) and the maximum likelihood
      method developed from the work of Nielsen and Yang (1998) are two widely used
      methods for detecting positive selection in homologous protein coding sequences.
      Both methods consider an excess of nonsynonymous (replacement) substitutions as
      evidence for positive selection. Previously published simulation studies
      comparing the performance of the two methods show contradictory results. Here we
      conduct a more thorough simulation study to cover and extend the parameter space
      used in previous studies. We also reanalyzed an HLA data set that was previously
      proposed to cause problems when analyzed using the maximum likelihood method. Our
      new simulations and a reanalysis of the HLA data demonstrate that the maximum
      likelihood method has good power and accuracy in detecting positive selection
      over a wide range of parameter values. Previous studies reporting poor
      performance of the method appear to be due to numerical problems in the
      optimization algorithms and did not reflect the true performance of the method.
      The parsimony method has a very low rate of false positives but very little power
      for detecting positive selection or identifying positively selected sites.

PMID- 15514075
TI  - Analysis of the estimators of the average coefficient of dominance of deleterious
      mutations.
AB  - We investigate the sources of bias that affect the most commonly used methods of
      estimation of the average degree of dominance (h) of deleterious mutations,
      focusing on estimates from segregating populations. The main emphasis is on the
      effect of the finite size of the populations, but other sources of bias are also
      considered. Using diffusion approximations to the distribution of gene
      frequencies in finite populations as well as stochastic simulations, we assess
      the behavior of the estimators obtained from populations at mutation-selection
      drift balance under different mutational scenarios and compare averages of h for
      newly arisen and segregating mutations. Because of genetic drift, the inferences
      concerning newly arisen mutations based on the mutation-selection balance theory
      can have substantial upward bias depending upon the distribution of h. In
      addition, estimates usually refer to h weighted by the homozygous deleterious
      effect in different ways, so that inferences are complicated when these two
      variables are negatively correlated. Due to both sources of bias, the widely used
      regression of heterozygous on homozygous means underestimates the arithmetic mean
      of h for segregating mutations, in contrast to their repeatedly assumed equality
      in the literature. We conclude that none of the estimators from segregating
      populations provides, under general conditions, a useful tool to ascertain the
      properties of the degree of dominance, either for segregating or for newly arisen
      deleterious mutations. Direct estimates of the average h from mutation
      accumulation experiments are shown to suffer some bias caused by purging
      selection but, because they do not require assumptions on the causes maintaining
      segregating variation, they appear to give a more reliable average dominance for
      newly arisen mutations.

PMID- 15514076
TI  - The HKA test revisited: a maximum-likelihood-ratio test of the standard neutral
      model.
AB  - We present a maximum-likelihood-ratio test of the standard neutral model, using
      multilocus data on polymorphism within species and divergence between species.
      The model is based on the Hudson-Kreitman-Aguade (HKA) test, but allows for an
      explicit test of selection at individual loci in a multilocus framework. We use
      coalescent simulations to show that the likelihood-ratio test statistic is
      conservative, particularly when the assumption of no recombination is violated.
      Application of the method to polymorphism data from 18 loci from a population of
      Arabidopsis lyrata provides significant evidence for a balanced polymorphism at a
      candidate locus thought to be linked to the centromere. The method is also
      applied to polymorphism data in maize, providing support for the hypothesis of
      directional selection on genes in the starch pathway.

PMID- 15514077
TI  - Genes encoding vitamin-K epoxide reductase are present in Drosophila and
      trypanosomatid protists.
AB  - Vitamin-K epoxide reductase is encoded by the VKORC1 gene in mammals and other
      vertebrates, which also have a paralog, VKORC1L1. Single homologs are present in
      basal deuterostome and insect genomes, including Drosophila, and three
      trypanosomatid protists. VKOR is therefore an ancient gene/protein that can be
      studied in the Drosophila model system.

PMID- 15514078
TI  - A novel solution for the time-dependent probability of gene fixation or loss
      under natural selection.
AB  - Kimura proposed a solution for the time-dependent probability of fixation, or
      loss, of a gene under selection. Example calculations suggest the formulas are
      prone to numerical inaccuracies. An alternative solution is proposed; the
      correctness of the solution is confirmed by numerically solving the Kolmogorov
      backward equation and by simulation.

PMID- 15514079
TI  - Maximum likelihood vs. minimum distance: searching for hills in the plain.

PMID- 15514080
TI  - A workshop report on wheat genome sequencing: International Genome Research on
      Wheat Consortium.
AB  - Sponsored by the National Science Foundation and the U.S. Department of
      Agriculture, a wheat genome sequencing workshop was held November 10-11, 2003, in
      Washington, DC. It brought together 63 scientists of diverse research interests
      and institutions, including 45 from the United States and 18 from a dozen foreign
      countries (see list of participants at http://www.ksu.edu/igrow). The objectives
      of the workshop were to discuss the status of wheat genomics, obtain feedback
      from ongoing genome sequencing projects, and develop strategies for sequencing
      the wheat genome. The purpose of this report is to convey the information
      discussed at the workshop and provide the basis for an ongoing dialogue, bringing
      forth comments and suggestions from the genetics community.

PMID- 15514081
TI  - Novel actions of estrogen receptor-beta on anxiety-related behaviors.
AB  - Estrogens are reported to have both anxiogenic and anxiolytic properties. This
      dichotomous neurobiological response to estrogens may be mediated by the
      existence of two distinct estrogen receptor (ER) systems, ERalpha and ERbeta. In
      brain, ERalpha plays a critical role in regulating reproductive neuroendocrine
      function, whereas ERbeta may be more important in regulating nonreproductive
      functions. To determine whether estrogen's anxiolytic actions could be mediated
      by ERbeta, we examined anxiety-related behaviors after treatment with ER subtype
      selective agonists. Ovariectomized female rats, divided into four treatment
      groups, were injected with the selective ERbeta agonist diarylpropionitrile
      (DPN), the ERalpha-selective agonist propyl-pyrazole-triol (PPT), 17beta
      estradiol, or vehicle daily for 4d. After injections, behavior was monitored in
      the elevated plus maze or open field. Rats treated with DPN showed significantly
      decreased anxiety-related behaviors in both behavioral paradigms. In the elevated
      plus maze, DPN significantly increased the number of open arm entries and time
      spent on the open arms of the maze. Furthermore, DPN significantly reduced,
      whereas PPT increased, anxiogenic behaviors such as the number of fecal boli and
      time spent grooming. In the open field, DPN-treated females made more rears,
      interacted more with a novel object, and spent more time in the middle of the
      open field than did control or PPT-treated rats. To confirm that DPN's anxiolytic
      actions are ER mediated, the nonselective ER antagonist tamoxifen was
      administered alone or in combination with DPN. Tamoxifen blocked the previously
      identified anxiolytic actions of DPN. Taken together, these findings suggest that
      the anxiolytic properties of estrogens are ERbeta mediated.

PMID- 15514082
TI  - Estrogen activates mitogen-activated protein kinase in native, nontransfected CHO
      K1, COS-7, and RAT2 fibroblast cell lines.
AB  - CHO-K1, COS-7, and Rat2 fibroblast cell lines are generally believed to be devoid
      of estrogen receptors (ERs) and have been widely used to study the functions of
      ER-alpha and ER-beta after transfection of their cDNAs. Numerous studies have
      demonstrated that transfected ER-alpha or ER-beta mediates estradiol-induced
      activation of multiple signaling pathways, including the MAPK/ERK pathways. We
      report here for the first time that both 17alpha-estradiol and 17beta-estradiol
      elicit activation of MAPK/ERK in native, nontransfected CHO-K1, COS-7, and Rat2
      fibroblast cell lines. We further report that, contrary to the generally held
      belief, these cell lines are not unresponsive to estradiol in their native,
      nontransfected state, and that this estrogen responsiveness is associated with
      estrogen binding. Using multiple ER antibodies, we failed to find ER-alpha or ER
      beta isoforms or even ER-X. In view of these findings, researchers, using such
      cells as models to investigate mechanisms of estrogen action, must always take
      into account the existence of endogenous estrogen binding proteins other than ER
      alpha, ER-beta, or ER-X.

PMID- 15514083
TI  - Central infusion of agouti-related peptide suppresses pulsatile luteinizing
      hormone release in the ovariectomized rhesus monkey.
AB  - Agouti-related peptide (AGRP), an endogenous melanocortin receptor antagonist, is
      a powerful orexigenic peptide when infused centrally. AGRP and neuropeptide Y
      (NPY), another orexigenic peptide, are colocated within the same neurons in the
      arcuate nucleus. Both NPY and AGRP mRNA expression increases during food
      restriction, a condition that is known to suppress the GnRH pulse generator and
      reproductive function. Although NPY has been shown previously to suppress LH
      secretion in the ovariectomized monkey, data on AGRP are lacking. In this study,
      we examined the effect of AGRP infusion into the third ventricle on pulsatile LH
      release in five adult monkeys. The 8-h protocol included a 3-h intraventricular
      saline infusion to establish baseline pulsatile LH release, followed by a 5-h
      infusion of AGRP (83-132) [5 microg/h (n=1) or 10 microg/h (n=4)]. In separate
      experiments, each animal received an 8-h saline treatment as a control. Blood
      samples were collected every 15 min for LH measurements. Cortisol levels were
      measured every 45 min. AGRP infusion significantly decreased LH pulse frequency
      (from a baseline of 0.74 +/- 0.07 pulse/h to 0.36 +/- 0.12 during AGRP infusion;
      P <0.01) and mean LH concentrations (to 41.1 +/- 7.5% of baseline by h 5 of AGRP
      infusion; P < 0.001). LH pulse amplitude was not modified by AGRP treatment. AGRP
      infusion also significantly increased cortisol release, as previously reported.
      The data demonstrate that central administration of AGRP inhibits pulsatile LH
      release in the monkey and suggest that AGRP, like NPY, may mediate the effect of
      a negative energy balance on the reproductive system by suppressing the GnRH
      pulse generator.

PMID- 15514084
TI  - Influence of ovarian ornithine decarboxylase in folliculogenesis and
      luteinization.
AB  - LH plays a relevant role in folliculogenesis, ovulation, and luteinization.
      Although ornithine decarboxylase (ODC), a key enzyme in polyamine biosynthesis,
      is a target of LH in the ovary, the functional significance of ODC induction has
      remained elusive. Our study reveals that the blockade of the induction of ovarian
      ODC by means of the specific inhibitor alpha-difluoromethylornithine (DFMO)
      affects folliculogenesis and luteinization. In immature female mice, DFMO was
      found to inhibit ovarian growth, the formation of Graafian follicles, and the
      secretion of progesterone and estradiol. In adult cycling females, the
      administration of DFMO on the evening/night of proestrus markedly decreased
      plasma progesterone levels at diestrus, which was associated to the decrease in
      the expression of steroidogenic factor 1, cytochrome cholesterol side chain
      cleavage enzyme, and steroidogenic acute regulatory protein in the ovary and to a
      reduced vascularization of the corpora lutea. These effects were not reverted by
      the administration of gonadotropins or prolactin. ODC immunoreactivity was also
      stimulated by LH in theca and granulosa cells of antral follicles but not in
      preantral follicles. Overall, these experiments demonstrate that elevated ODC
      values found in the ovary of immature and adult mice play a relevant function in
      ovarian physiology and that ODC/polyamines must be considered as important
      mediators of some of the effects of LH on follicular development and
      luteinization.

PMID- 15514086
TI  - Testosterone replacement therapy induces spermatogenesis and partially restores
      fertility in luteinizing hormone receptor knockout mice.
AB  - Testosterone (T) is essential for spermatogenesis, fertility, and maintenance of
      the male phenotype. We analyzed in hypogonadal LH receptor knockout (LuRKO) male
      mice whether T treatment can restore their phenotype, spermatogenesis, and
      fertility. In LuRKO mice, spermatogenesis is arrested at round spermatids, adult
      type Leydig cells are absent, T production is dramatically decreased, the animals
      are cryptorchid, and their accessory sex organs are atrophic. T replacement
      therapy from 21 d of life for 60 or 120 d in LuRKO mice induced a male phenotype
      macroscopically indistinguishable from that of wild-type littermates as well as
      full spermatogenesis and testicular descent. Thus, the absence of LH-dependent
      prepubertal androgen priming is not necessary for subsequent maturation of the
      male phenotype. Conspicuously, some abnormalities remained in epididymal
      histology after T treatment despite normal expression of several epididymis
      specific genes in caput epididymis. The mice displayed normal mating behavior,
      although at lower frequency than wild-type controls. The spermatozoa were able to
      fertilize oocytes, but their impaired passage from epididymis to uterus was
      apparent. The mice remained subfertile, because only 9% of all breedings resulted
      in pregnancy, and only two of 13 mice (15%) were fertile. Moreover, inflammation
      in epididymides and prostate was found in many T-treated LuRKO mice, which
      probably impaired sperm transport and contributed to their high rate of
      subfertility. In conclusion, T replacement initiated prepubertally only partially
      restores the fertility of LuRKO mice, even though most features of the male
      phenotype recover. Full fertility may require higher and/or earlier postnatal T
      exposure or production of other Leydig cell factors lacking in this model.

PMID- 15514087
TI  - Pubertal and adult Leydig cell function in Mullerian inhibiting substance
      deficient mice.
AB  - Mullerian inhibiting substance (MIS) causes Mullerian duct regression during
      sexual differentiation and regulates postnatal Leydig cell development. MIS
      knockout (MIS-KO) mice with targeted deletions of MIS develop Leydig cell
      hyperplasia, but their circulating androgen concentrations are reportedly
      unaltered. We compared reproductive hormone profiles, androgen biosynthesis, and
      the expression of key steroidogenic and metabolic enzymes in MIS-KO and wild-type
      (WT) mice at puberty (36 d) and sexual maturity (60 d). In pubertal animals,
      basal testosterone and LH concentrations in plasma were lower in MIS-KO than WT
      mice, whereas human chorionic gonadotropin-stimulated testosterone concentrations
      were similar. In adults, basal LH, and both basal and human chorionic
      gonadotropin (hCG)-stimulated testosterone concentrations were similar. Purified
      Leydig cells from pubertal MIS-KO mice had lower testosterone but higher
      androstanediol and androstenedione production rates. In contrast, testosterone,
      androstanediol, and androstenedione production rates were all lower in adult MIS
      KO Leydig cells. Steroidogenic acute regulatory protein expression was lower in
      pubertal MIS-KO mice compared with WT, whereas 17beta-hydroxy-steroid
      dehydrogenase and 5alpha-reductase were greater, and P450c17 and P450scc were
      similar. The expression of steroidogenic acute regulatory protein and 17beta
      hydroxysteroid dehydrogenase was lower in adult MIS-KO mice, whereas that of
      5alpha-reductase, P450c17, and P450scc was similar. Collectively, these results
      suggest that in the absence of MIS, Leydig cells remain less differentiated,
      causing an altered intratesticular androgen milieu that may contribute to the
      infertility of MIS-KO mice. In immature mice, this deficit in steroidogenic
      capacity appears to be mediated by a direct loss of MIS action in Leydig cells as
      well as by indirect effects via the hypothalamic-pituitary-gonadal axis.

PMID- 15514085
TI  - Quantitative trait loci associated with elevated thyroid-stimulating hormone in
      the Wistar-Kyoto rat.
AB  - Thyroid hormones are essential for the regulation of developmental and
      physiological processes. The genetic factors underlying naturally occurring
      variability in mammalian thyroid function are, however, only partially
      understood. Genetic control of thyroid function can be studied with animal models
      such as the inbred Wistar-Kyoto (WKY) rat strain. Previous studies established
      that WKY rats have elevated TSH, slightly elevated total T3, and normal total T4
      levels compared with Wistar controls. The present study confirmed a persistent 24
      h elevation of TSH in WKY rats compared with the Fisher 344 (F344) rat, another
      inbred strain. Acute T3 challenge (25 microg/100 g body weight ip) suppressed
      serum TSH and T4 levels in both strains. Quantitative trait locus analysis of
      elevated TSH in a reciprocally bred WKY x F344 F2 population identified one
      highly significant locus on chromosome 6 (LOD=11.7, TSH-1) and one suggestive
      locus on chromosome 5 (LOD=2.3, TSH-2). The confidence interval of TSH-1 contains
      the TSH receptor and type 2 deiodinase genes, and TSH-2 contains the type 1
      deiodinase gene. The WKY alleles of each gene contain sequence alterations, but
      additional studies are indicated to identify the specific gene or genes
      responsible for altered regulation of the thyroid axis. These findings suggest
      that one or more genetic alterations within the TSH-1 locus significantly
      contribute to the altered thyroid function tests of the WKY rat.

PMID- 15514088
TI  - VPAC2-R mediates the lipolytic effects of pituitary adenylate cyclase-activating
      polypeptide/vasoactive intestinal polypeptide in primary rat adipocytes.
AB  - The neuropeptides pituitary adenylate cyclase-activating polypeptide (PACAP) and
      vasoactive intestinal polypeptide (VIP) are structurally and functionally
      related. Their actions have been shown to be mediated by three different receptor
      subtypes: PAC1-R, which has exclusive affinity for PACAP, and VPAC1-R and VPAC2
      R, which have equal affinity for PACAP and VIP. We recently showed that PACAP38
      induces lipolysis in rat adipocytes, and in the present study we examined whether
      VIP has similar effects and which of the three receptors mediates this PACAP/VIP
      action. We showed by RT-PCR that all three receptor subtypes are present in rat
      adipocytes. We demonstrated that VIP (1-100 nm), like PACAP38, stimulates
      lipolysis in isolated adipocytes, as determined by glycerol release. By a
      pharmacological approach, using antagonists and agonists specific for the
      receptor subtypes, we elucidated the mechanisms by which PACAP38 and VIP mediate
      their lipolytic effects. We found that antagonists of PAC1-R [PACAP(6-38)] and
      VPAC1-R (PG97-269) did not affect lipolysis induced by 0.1-100 nm PACAP38 or VIP,
      and that a VPAC1-R agonist [K15, R16, L27VIP(1-7)GRF(8-27)] did not affect
      lipolysis at 1-1000 nm. However, two different VPAC2-R agonists [Hexa-VIP(1-28)
      and Ro25-1553] clearly mimicked the lipolytic effect of PACAP38 and VIP. In
      addition, the VPAC2-R antagonist PG99-465 (100 nm) caused right-shifted dose
      response curves of PACAP38- and VIP-induced lipolysis. These results therefore
      provide evidence that all three PACAP/VIP receptor subtypes are expressed in
      primary rat adipocytes, but that the VPAC2-R subtype is responsible for mediating
      the lipolytic effects induced by PACAP38 and VIP.

PMID- 15514089
TI  - Suppressor of cytokine signaling-3 Provides a novel interface in the cross-talk
      between angiotensin II and insulin signaling systems.
AB  - Angiotensin II inhibits insulin-induced activation of phosphatidylinositol 3
      kinase through a mechanism, at least in part, dependent on serine phosphorylation
      of the insulin receptor and insulin receptor substrates (IRS)-1/2. Recent
      evidence shows that suppressor of cytokine signaling-3 (SOCS-3) is induced by
      insulin and angiotensin II and participates in the negative control of further
      stimulation of each of these signaling systems independently. In the present
      study, we evaluated the interaction of angiotensin II-induced SOCS-3 with the
      insulin signaling pathway in the heart of living rats. A single iv dose of
      angiotensin II promotes a significant increase of SOCS-3 in heart, an effect that
      lasts up to 180 min. Once induced, SOCS-3 interacts with the insulin receptor,
      JAK-2, IRS-1, and IRS-2. The inhibition of SOCS-3 expression by a phosphorthioate
      modified antisense oligonucleotide partially restores angiotensin II-induced
      inhibition of insulin-induced insulin receptor, IRS-1 and IRS-2 tyrosine
      phosphorylation, and IRS-1 and IRS-2 association with p85-phosphatidylinositol 3
      kinase and [Ser473] phosphorylation of Akt. Moreover, the inhibition of SOCS-3
      expression partially reverses angiotensin II-induced inhibition of insulin
      stimulated glucose transporter-4 translocation to the cell membrane. These
      results are reproduced in isolated cardiomyocytes. Thus, SOCS-3 participates, as
      a late event, in the negative cross-talk between angiotensin II and insulin,
      producing an inhibitory effect on insulin-induced glucose transporter-4
      translocation.

PMID- 15514090
TI  - Evidence that the amino-terminal composition of non-(1-84) parathyroid hormone
      fragments starts before position 19.
AB  - BACKGROUND: Non-(1-84) parathyroid hormone (PTH) fragments are large C-terminal
      fragments of PTH with a partially preserved N-terminal structure. They differ
      from other C-terminal PTH fragments, which do not have an N-terminal structure
      and do not react in intact PTH assays. We aimed to identify the minimal N
      terminal structure common to all non-(1-84) PTH fragments. METHODS: Sera obtained
      from six healthy individuals and six patients with primary hyperparathyroidism,
      and six serum pools from dialysis patients with different PTH concentrations were
      fractionated by HPLC and analyzed by four different PTH assays. Each assay was
      characterized by saturation analysis of its detection antibody and capacity to
      react with different PTH fragments. Human PTH(1-84) [hPTH(1-84)] calibrators were
      normalized to an in-house hPTH(1-84) calibrator. RESULTS: The cyclase-activating
      PTH (CA-PTH) assay had an early (1, 2,) epitope and reacted only with hPTH(1-84).
      The other assays had epitopes in region (13-34). Total and intact PTH assays had
      epitopes proximal to position 18 and reacted equally well with hPTH(1-84) and
      hPTH(7-84), and the Elecsys PTH assay had an epitope distal to position 19, being
      saturable by hPTH(18-48) and also reacting with [Tyr(34)]hPTH(19-84). The HPLC
      profiles obtained with these assays showed that non-(1-84) PTH fragments did not
      react in the CA-PTH assay, as expected. The amount of non-(1-84) PTH detected by
      the other three assays was similar when the assay results were normalized to a
      common calibrator. CONCLUSIONS: The results suggest that the amount of non-(1-84)
      PTH detected by epitopes proximal or distal to position 19 of the PTH structure
      is identical, indicating a common minimum structure starting before position 19.
      This in turn points to a probable high-affinity interaction with the C-PTH
      receptor, as observed previously with [Tyr(34)]hPTH(19-84) in various cell lines
      and in mouse osteocytes with PTH/PTHrP type I receptor ablation.

PMID- 15514091
TI  - Latex immunoturbidimetric assay for soluble fibrin complex.
AB  - BACKGROUND: Soluble fibrin complex (SFC), composed of fibrin monomer and
      fibrinogen derivatives, is known to exist in the circulating blood in patients
      with thrombosis. Its detection and quantification are useful for obtaining
      information about the condition and degree of intravascular coagulation in early
      stage thrombosis, but there is no rapid method to measure SFC in plasma for
      clinical use. METHODS: We obtained a monoclonal antibody that specifically reacts
      with SFC, with desAA-fibrin as the immunogen, and developed a rapid and sensitive
      latex immunoturbidimetric assay (LIA) using latex-immobilized anti-SFC monoclonal
      antibody. The assay system was based on the increase in turbidity induced by the
      reaction of the latex-immobilized anti-SFC monoclonal antibody with SFC in
      plasma, and the assay procedure was fully automated on a Hitachi 911 analyzer.
      RESULTS: The method had an analytical range of 3-300 mg/L. Intra- and interassay
      precision studies indicated that this system provided reproducible data (CVs
      <3.0% and <2.0%, respectively). The assay detection limit was <0.5 mg/L. There
      was no interference from bilirubin (up to 440 mg/L), hemoglobin (up to 9.6 g/L),
      Intralipid (up to 10%), D-dimer (up to 200 mg/L), and rheumatoid factor (up to
      470 000 IU/L). SFC concentrations in plasma from patients with thrombotic
      diseases [mean (SD), 48.9 (57.6) mg/L; n = 160) were significantly higher than
      those in plasma from healthy individuals [1.8 (2.1) mg/L; P <0.001; n = 304].
      CONCLUSION: In terms of linearity, precision, and sensitivity, the LIA, performed
      on a Hitachi 911 automated analyzer, may be useful for measurement of SFC in
      plasma.

PMID- 15514092
TI  - Three novel mutations in the apolipoprotein E gene in a sample of individuals
      with type 2 diabetes mellitus.
AB  - BACKGROUND: Apolipoprotein E (apoE) is found in association with triglyceride
      rich lipoproteins and is the ligand for the removal of these particles from the
      plasma. Genetic variations in exon 4 lead to three common gene variants: E2, E3,
      and E4. METHODS: We performed apoE genotyping in 765 individuals with type 2
      diabetes. RESULTS: We identified three new variant heteroduplex patterns.
      Sequencing of these variants revealed three novel mutations that were related to
      biochemical and clinical characteristics. One mutation produced a frameshift at
      amino acid position 166, which predicted termination of protein synthesis. This
      individual had a heteroduplex pattern and sequence of E3E3, which was associated
      with a change in the plasma isoelectric focusing pattern and a 70% lower plasma
      concentration of apoE compared with healthy individuals. The other mutations were
      both single base changes. A CGC>CAC change at amino acid position 150 predicted a
      substitution of Arg>His. This individual had a heteroduplex pattern and sequence
      of E2E2, which was not associated with major changes in plasma lipids or apoE
      concentration. The third individual had a CGC>CCC base change at amino acid
      position 114, which predicted an Arg>Pro change. This person had a heteroduplex
      pattern and sequence of E3E3, higher plasma total cholesterol, and moderately
      decreased plasma apoE. CONCLUSIONS: The frequency of new mutations in this sample
      (1 in 255) is higher than that of a healthy population (1 in 7900). Further
      screening for common apoE gene variants in individuals at risk for dyslipidemia
      may reveal abnormal heteroduplex patterns and uncover further mutations in this
      important lipid-regulating gene.

PMID- 15514093
TI  - Diagnosis of methylmalonic acidemia from dried blood spots by HPLC and
      intramolecular-excimer fluorescence derivatization.

PMID- 15514094
TI  - Sequencing of genomic DNA by combined amplification and cycle sequencing
      reaction.
AB  - BACKGROUND: Despite considerable advances, DNA sequencing has remained somewhat
      time-consuming and expensive, requiring three separate steps to generate
      sequencing products from a template: amplification of the target sequence;
      purification of the amplified product; and a sequencing reaction. Our aim was to
      develop a method to routinely combine PCR amplification and cycle sequencing into
      one single reaction, enabling direct sequencing of genomic DNA. METHODS: Combined
      amplification and sequencing reactions were set up with Big Dye sequencing
      reagents (Applied Biosystems) supplemented with variable amounts of forward and
      reverse primers, deoxynucleotide triphosphates (dNTPs), and input DNA. Reactions
      were thermal-cycled for 35 or 45 cycles. Products were analyzed by capillary
      electrophoresis to detect sequencing products. RESULTS: Reactions using two
      oligonucleotide primers at a ratio of 5:1 (500 nM primer 1 and 100 nM primer 2),
      125 microM supplemental dNTPs, and 35-45 thermal cycles optimally supported
      combined amplification and cycle sequencing reactions. Our results suggest that
      these reactions are dominated by PCR during early cycles and convert to cycle
      sequencing in later cycles. We used this technique for a variety of sequencing
      applications, including the identification of germline mutations/polymorphisms in
      the Factor V and BRCA2 genes, sequencing of tumor DNA to identify somatic
      mutations in the DPC4/SMADH4 and FLT3 genes, and sequencing of 16S ribosomal DNA
      for bacterial speciation. CONCLUSIONS: PCR amplification and cycle sequencing can
      be combined into a single reaction using the conditions described. This technique
      allows direct sequencing of genomic DNA, decreasing the cost and labor involved
      in gene sequencing.

PMID- 15514095
TI  - Establishment, value assignment, and characterization of new WHO reference
      reagents for six molecular forms of human chorionic gonadotropin.
AB  - BACKGROUND: The International Federation of Clinical Chemistry and Laboratory
      Medicine (IFCC) established a Working Group to investigate means of improving the
      comparability of immunoassays for human chorionic gonadotropin (hCG), which was
      selected as a prototype glycoprotein analyte. The Working Group identified
      development of unambiguous nomenclature and production of new highly purified
      International Reference Reagents calibrated in substance concentrations as its
      primary objectives. METHODS: Preparations of intact hCG, nicked hCG, hCG beta
      subunit, nicked hCG beta-subunit, hCG alpha-subunit, and hCG beta-core fragment
      were purified from a crude urinary hCG preparation, ampouled, lyophilized, and
      assigned values in substance concentrations (mol/L). Value assignment and
      accelerated degradation studies were carried out in accordance with WHO protocols
      for International Reference Reagents. RESULTS: The ampouled standards were
      assigned final values based on the recovery of immunoreactive material after
      reconstitution. The degradation studies showed that the standards were highly
      stable. CONCLUSIONS: The nomenclature of hCG-related molecules and immunoassays
      has been adopted by the IFCC, and the standards prepared and characterized by the
      Working Group have been formally adopted by the WHO as the First International
      Reference Reagents for six hCG-related molecules. These developments will enable
      better understanding of what assays for hCG measure and should ultimately help to
      improve the clinical application of these assays.

PMID- 15514096
TI  - Panel of genes transcriptionally up-regulated in squamous cell carcinoma of the
      cervix identified by representational difference analysis, confirmed by
      macroarray, and validated by real-time quantitative reverse transcription-PCR.
AB  - BACKGROUND: The Pap smear is currently the most widely used method of screening
      for squamous cell carcinoma of the cervix (SCCC). Because it is based on cell
      morphology, it is subject to variability in interpretation. Sensitive molecular
      markers capable of differentiating cancerous samples from noncancerous ones would
      be beneficial in this regard. METHODS: We performed representational difference
      analysis (RDA) using paired, noncancerous (normal) and cancerous (disease)
      tissues taken from the same specimen obtained from a single patient with a
      confirmed diagnosis of SCCC. Linearly amplified cDNA from normal and diseased
      tissues of the original patient and seven others were hybridized to DNA
      macroarrays containing the candidate gene transcript fragments. Real-time
      quantitative reverse transcription-PCR was used to validate the macroarray
      results. RESULTS: RDA identified a candidate pool of 65 transcript fragments up
      regulated in diseased tissue compared with normal tissue. Forty-one transcripts
      were found to be up-regulated in diseased compared with normal tissue in at least
      one half the patients by macroarray hybridization. Eleven of those genes were
      selected for real-time quantitative reverse transcription-PCR analysis, and all
      were confirmed as transcriptionally up-regulated in cancer compared with normal
      tissue in at least one half the patients. CONCLUSIONS: RDA using tissues from a
      single patient identified gene fragments confirmed to be transcriptionally up
      regulated in SCCC both in the original patient and in seven others. The confirmed
      genes have a variety of functions and also have the potential to serve as
      diagnostic or prognostic markers.

PMID- 15514097
TI  - Liquid chromatography-tandem mass spectrometry quantification of
      globotriaosylceramide in plasma for long-term monitoring of Fabry patients
      treated with enzyme replacement therapy.

PMID- 15514098
TI  - Impact of formaldehyde on the in vitro proportion of fetal DNA in maternal plasma
      and serum.

PMID- 15514099
TI  - Liver dysfunction and steatosis in familial hypobetalipoproteinemia.
AB  - A 32-year-old man presented with increases in serum alanine aminotransferase
      activity, iron concentration, and transferrin saturation, suggestive of hepatic
      dysfunction and iron overload. In addition, he had unusually low plasma
      concentrations of LDL-cholesterol and apolipoprotein (apo) B. Hepatic
      ultrasonography was consistent with fatty liver. On liver biopsy, marked
      steatosis and moderate to marked iron deposition were observed. The patient was
      found to carry the HFE C282Y and H63D mutations, which are associated with
      hereditary hemochromatosis, and the alpha(1)-antitrypsin PiZ variant. An
      immunoblot of plasma for apoB showed the presence of a truncated apoB species,
      indicative of familial hypobetalipoproteinemia. DNA sequence analysis revealed
      that the patient was heterozygous for the apoB-80.5 (c.11040T>G) mutation. This
      unique case shows an unusual combination of underlying disorders that could all
      be contributing to liver dysfunction and fatty liver.

PMID- 15514100
TI  - Plasma F2-isoprostanes and coronary artery calcification: the CARDIA Study.
AB  - BACKGROUND: Oxidation of lipids in lipoproteins and cells may initiate and
      enhance the early development of cardiovascular disease. METHOD AND RESULTS: We
      assayed F(2)-isoprostanes, oxidation products of arachidonic acid, by gas
      chromatography-mass spectrometry in a biracial cohort of 2850 young healthy adult
      men and women. Coronary artery calcification (CAC), a component of coronary
      artery atherosclerosis, was detectable in 10% of the cohort and appeared to be in
      its initial stages (Agatston scores <20 in 47% and <100 in 83% of CAC-positive
      participants). After adjusting for sex, clinical site, age, and race, the
      presence of any CAC was 24% more likely among those with high vs low
      concentrations of F(2)-isoprostanes [odds ratio (OR) = 1.24 per 92.2 pmol/L (32.7
      ng/L; 1 SD of F(2)-isoprostanes); 95% confidence interval (CI), 1.09-1.41]. The
      OR was only slightly attenuated [1.18 per 92.2 pmol/L (32.7 ng/L); CI, 1.02-1.38]
      after further adjustment for body mass index, smoking, serum lipids, C-reactive
      protein, antioxidant supplementation use, diabetes, and blood pressure. As a
      continuous variable, the Agatston score increased by 6.9% per 92.2 pmol/L (32.7
      ng/L) of F(2)-isoprostane concentration (P <0.01). Whereas CAC prevalence was
      lower in women than men, mean (SD), F(2)-isoprostanes were higher in women {190
      (108.9) pmol/L [67.4 (38.6) ng/L]} than in men {140.4 (55.6) pmol/L [49.8 (19.7)
      ng/L]}. Nevertheless, F(2)-isoprostanes were associated with an increased risk of
      CAC in both sexes. CONCLUSION: This association between increased concentrations
      of circulating F(2)-isoprostanes and CAC in young healthy adults supports the
      hypothesis that oxidative damage is involved in the early development of
      atherosclerosis.

PMID- 15514101
TI  - Laboratory assessment of oxygenation in methemoglobinemia.
AB  - BACKGROUND: This case conference reviews laboratory methods for assessing
      oxygenation status: arterial blood gases, pulse oximetry, and CO-oximetry.
      Caveats of these measurements are discussed in the context of two
      methemoglobinemia cases. CASES: Case 1 is a woman who presented with increased
      shortness of breath, productive cough, chest pain, nausea, fever, and cyanosis.
      CO-oximetry indicated a carboxyhemoglobin (COHb) fraction of 24.9%. She was
      unresponsive to O(2) therapy, and no source of carbon monoxide could be noted.
      Case 2 is a man who presented with syncope, chest tightness, and signs of
      cyanosis. His arterial blood was dark brown, and CO-oximetry showed a
      methemoglobin (MetHb) fraction of 23%. ISSUES: Oxygen saturation (So(2)) can be
      measured by three approaches that are often used interchangeably, although the
      measured systems are quite different. Pulse oximetry is a noninvasive,
      spectrophotometric method to determine arterial oxygen saturation (S(a)O(2)). CO
      oximetry is a more complex and reliable method that measures the concentration of
      hemoglobin derivatives in the blood from which various quantities such as
      hemoglobin derivative fractions, total hemoglobin, and saturation are calculated.
      Blood gas instruments calculate the estimated O(2) saturation from empirical
      equations using pH and Po(2) values. In most patients, the results from these
      methods will be virtually identical, but in cases of increased dyshemoglobin
      fractions, including methemoglobinemia, it is crucial that the distinctions and
      limitations of these methods be understood. CONCLUSIONS: So(2) calculated from pH
      and Po(2) should be interpreted with caution as the algorithms used assume normal
      O(2) affinity, normal 2,3-diphosphoglycerate concentrations, and no
      dyshemoglobins or hemoglobinopathies. CO-oximeter reports should include the
      dyshemoglobin fractions in addition to the oxyhemoglobin fraction. In cases of
      increased MetHb fraction, pulse oximeter values trend toward 85%, underestimating
      the actual oxygen saturation. Hemoglobin M variants may yield normal MetHb and
      increased COHb or sulfhemoglobin fractions measured by CO-oximetry.

PMID- 15514102
TI  - Inhalation of carbon monoxide prevents liver injury and inflammation following
      hind limb ischemia/reperfusion.
AB  - The induction of heme oxygenase (HO), the rate limiting enzyme in the conversion
      of heme into carbon monoxide (CO) and biliverdin, limits liver injury following
      remote trauma such as hind limb ischemia/reperfusion (I/R). Using intravital
      video microscopy, we tested the hypothesis that inhaled CO (250 ppm) would mimic
      HO-derived liver protection. Hind limb I/R significantly decreased sinusoidal
      diameter and volumetric flow, increased leukocyte accumulation within sinusoids,
      increased leukocyte rolling and adhesion within postsinusoidal venules, and
      significantly increased hepatocyte injury compared with naive animals. Inhalation
      of CO alone did not alter any microcirculatory or inflammatory parameters.
      Inhalation of CO following I/R restored volumetric flow, decreased stationary
      leukocytes within sinusoids, decreased leukocyte rolling and adhesion within
      postsinusoidal venules, and significantly reduced hepatocellular injury following
      hind limb I/R. HO inhibition did not alter microcirculatory parameters in naive
      mice, but did increase inflammation, as well as increase hepatocyte injury
      following hind limb I/R. Inhalation of CO during HO inhibition significantly
      reduced such microcirculatory deficits, hepatic inflammation, and injury in
      response to hind limb I/R. In conclusion, these results suggest that HO-derived
      hepatic protection is mediated by CO, and inhalation of low concentrations of CO
      may represent a novel therapeutic approach to prevent remote organ injury during
      systemic inflammatory response syndrome, or SIRS.

PMID- 15514103
TI  - Soluble tumor necrosis factor (TNF) receptor-1 induces apoptosis via reverse TNF
      signaling and autocrine transforming growth factor-beta1.
AB  - The pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) plays a
      central role in inflammatory disorders. Transmembrane TNF-alpha and its two
      receptors are cleaved by the proteinase TNF-alpha converting enzyme (TACE),
      resulting in appreciable serum levels of soluble TNF-alpha and soluble TNF-alpha
      receptors (sTNFR1 and -2). The only known functions of sTNFR1 are to antagonize
      and buffer circulating TNF-alpha. Here, we present evidence that sTNFR1 exerts
      immunoregulatory functions by induction of apoptosis in monocytes through reverse
      signaling via transmembrane TNF-alpha. sTNFR1-induced apoptosis is independent of
      death receptor pathways but depends on autocrine transforming growth factor (TGF)
      beta1 signaling through the mitogen-activated protein kinase p38alpha. This novel
      mechanism has implications for understanding the physiological role of sTNFR1 and
      for TNF-alpha-blocking therapies of autoimmune diseases.

PMID- 15514104
TI  - Oxidant stress and constrictor reactivity impair cerebral artery dilation in
      obese Zucker rats.
AB  - This study tested the hypothesis that evolution of the metabolic syndrome in
      obese Zucker rats (OZR) leads to impaired dilator reactivity of cerebral
      resistance arteries vs. responses determined in lean Zucker rats (LZR). Middle
      cerebral arteries (MCA) from 17-wk-old male LZR and OZR were isolated and
      cannulated with glass micropipettes. Vascular reactivity was assessed in response
      to challenge with ACh, sodium nitroprusside (SNP), reductions and elevations in
      Po2, 5-HT, and increased intralumenal pressure. Vessels were treated with the
      free radical scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (tempol) to
      assess the role of superoxide production in altering reactivity, and passive
      vascular wall mechanics was assessed in each vessel. Vascular superoxide
      production was assessed in isolated arteries using fluorescence microscopy.
      Vessel dilation to ACh and hypoxia was impaired in OZR vs. LZR, although
      responses to SNP were normal. Vessel constriction to 5-HT, elevated Po2, and
      elevated intralumenal pressure was enhanced in OZR vs. LZR. Fluorescence
      microscopy demonstrated an increased superoxide production in arteries of OZR vs.
      LZR, correctable by incubation with tempol. Although treatment of vessels from
      OZR with tempol improved dilation to ACh and hypoxia, constrictor responses to 5
      HT, elevated Po2, and pressure were not altered by tempol treatment. Indexes of
      vessel wall mechanics were comparable between groups. These results suggest that
      vasodilator reactivity of MCA of OZR in response to endothelium-dependent dilator
      stimuli is impaired vs. LZR and that this may represent a reduced bioavailability
      of signaling molecules due to oxidant scavenging. However, oxidative stress
      independent increases in myogenic tone and constrictor reactivity may contribute
      to blunted dilator responses of cerebral microvessels.

PMID- 15514105
TI  - Maternal protein restriction leads to hyperinsulinemia and reduced insulin
      signaling protein expression in 21-mo-old female rat offspring.
AB  - Human adult diseases such as cardiovascular disease, hypertension, and type 2
      diabetes have been epidemiologically linked to poor fetal growth and development.
      Male offspring of rat dams fed a low-protein (LP) diet during pregnancy and
      lactation develop diabetes with concomitant alterations in their insulin
      signaling mechanisms. Such associations have not been studied in female
      offspring. The aim of this study was to determine whether female LP offspring
      develop diabetes in later life. Control and LP female offspring groups were
      obtained from rat dams fed a control (20% protein) or an isocaloric (8% protein)
      diet, respectively, throughout pregnancy and lactation. Both groups were weaned
      and maintained on 20% normal laboratory chow until 21 mo of age when they
      underwent intravenous glucose tolerance testing (IVGTT). Fasting glucose was
      comparable between the two groups; however, LP fasting insulin was approximately
      twofold that of controls (P < 0.02). Glucose tolerance during IVGTT was
      comparable between the two groups; however, LP peak plasma insulin at 4 min was
      approximately threefold higher than in controls (P < 0.001). LP plasma insulin
      area under the curve was 1.9-fold higher than controls (P < 0.02). In Western
      blots, both muscle protein kinase C-zeta expression and p110beta-associated
      p85alpha in abdominal fat were reduced (P < 0.05) in LPs. Hyperinsulinemia in
      response to glucose challenge coupled with attenuation of certain insulin
      signaling molecules imply the development of insulin resistance in LP muscle and
      fat. These observations suggest that intrauterine protein restriction leads to
      insulin resistance in females in old age and, hence, an increased risk of type 2
      diabetes.

PMID- 15514106
TI  - Signaling for myocardial depression in hemorrhagic shock: roles of Toll-like
      receptor 4 and p55 TNF-alpha receptor.
AB  - Hemorrhagic shock causes myocardial contractile depression. Although this
      myocardial disorder is associated with increased expression of tumor necrosis
      factor-alpha (TNF-alpha), the role of TNF-alpha as a myocardial depressant factor
      in hemorrhagic shock remains to be determined. Moreover, it is unclear which TNF
      alpha receptor mediates the myocardial depressive effects of TNF-alpha. Toll-like
      receptor 4 (TLR4) regulates cellular expression of proinflammatory mediators
      following lipopolysaccharide stimulation and may be involved in the tissue
      inflammatory response to injury. The contribution of TLR4 signaling to tissue TNF
      alpha response to hemorrhagic shock and TLR4's role in myocardial depression
      during hemorrhagic shock are presently unknown. We examined the relationship of
      TNF-alpha production to myocardial depression in a mouse model of nonresuscitated
      hemorrhagic shock, assessed the influence of TLR4 mutation, resulting in
      defective signaling, on TNF-alpha production and myocardial depression, and
      determined the roles of TNF-alpha and TNF-alpha receptors in myocardial
      depression using a gene knockout (KO) approach. Hemorrhagic shock resulted in
      increased plasma and myocardial TNF-alpha (4.9- and 4.5-fold, respectively) at 30
      min and induced myocardial contractile depression at 4 h. TLR4 mutation abolished
      the TNF-alpha response and attenuated myocardial depression (left ventricular
      developed pressure of 43.0 +/- 6.2 mmHg in TLR4 mutant vs. 30.0 +/- 3.6 mmHg in
      wild type, P < 0.05). TNF-alpha KO also attenuated myocardial depression in
      hemorrhagic shock, and the p55 receptor KO, but not the p75 receptor KO, mimicked
      the effect of TNF-alpha KO. The results suggest that TLR4 plays a novel role in
      signaling to the TNF-alpha response during hemorrhagic shock and that TNF-alpha
      through the p55 receptor activates a pathway leading to myocardial depression.
      Thus TLR4 and the p55 TNF-alpha receptor represent therapeutic targets for
      preservation of cardiac mechanical function during hemorrhagic shock.

PMID- 15514107
TI  - Genomic profiling by DNA amplification of laser capture microdissected tissues
      and array CGH.
AB  - Comparative genomic hybridization by means of BAC microarrays (array CGH) allows
      high-resolution profiling of copy-number aberrations in tumor DNA. However,
      specific genetic lesions associated with small but clinically relevant tumor
      areas may pass undetected due to intra-tumor heterogeneity and/or the presence of
      contaminating normal cells. Here, we show that the combination of laser capture
      microdissection, phi29 DNA polymerase-mediated isothermal genomic DNA
      amplification, and array CGH allows genomic profiling of very limited numbers of
      cells. Moreover, by means of simple statistical models, we were able to bypass
      the exclusion of amplification distortions and variability prone areas, and to
      detect tumor-specific chromosomal gains and losses. We applied this new combined
      experimental and analytical approach to the genomic profiling of colorectal
      adenomatous polyps and demonstrated our ability to accurately detect single copy
      gains and losses affecting either whole chromosomes or small genomic regions from
      as little as 2 ng of DNA or 1000 microdissected cells.

PMID- 15514108
TI  - Hypervariable genes--experimental error or hidden dynamics.
AB  - In a homogeneous group of samples, not all genes of high variability stem from
      experimental errors in microarray experiments. These expression variations can be
      attributed to many factors including natural biological oscillations or metabolic
      processes. The behavior of these genes can tease out important clues about
      naturally occurring dynamic processes in the organism or experimental system
      under study. We developed a statistical procedure for the selection of genes with
      high variability denoted hypervariable (HV) genes. After the exclusion of low
      expressed genes and a stabilizing log-transformation, the majority of genes have
      comparable residual variability. Based on an F-test, HV genes are selected as
      having a statistically significant difference from the majority of variability
      stabilized genes measured by the 'reference group'. A novel F-test clustering
      technique, further noted as 'F-means clustering', groups HV genes with similar
      variability patterns, presumably from their participation in a common dynamic
      biological process. F-means clustering establishes, for the first time, groups of
      co-expressed HV genes and is illustrated with microarray data from patients with
      juvenile rheumatoid arthritis and healthy controls.

PMID- 15514109
TI  - High sensitivity EndoV mutation scanning through real-time ligase proofreading.
AB  - The ability to associate mutations in cancer genes with the disease and its
      subtypes is critical for understanding oncogenesis and identifying biomarkers for
      clinical diagnosis. A two-step mutation scanning method that sequentially used
      endonuclease V (EndoV) to nick at mismatches and DNA ligase to reseal incorrectly
      or nonspecifically nicked sites was previously developed in our laboratory.
      Herein we report an optimized single-step assay that enables ligase to proofread
      EndoV cleavage in real-time under a compromise between buffer conditions. Real
      time proofreading results in a dramatic reduction of background cleavage. A
      universal PCR strategy that employs both unlabeled gene-specific primers and
      labeled universal primers, allows for multiplexed gene amplification and
      precludes amplification of primer dimers. Internally labeled PCR primers
      eliminate EndoV cleavage at the 5' terminus, enabling high-throughput capillary
      electrophoresis readout. Furthermore, signal intensity is increased and artifacts
      are reduced by generating heteroduplexes containing only one of the two possible
      mismatches (e.g. either A/C or G/T). The single-step assay improves sensitivity
      to 1:50 and 1:100 (mutant:wild type) for unknown mutations in the p53 and K-ras
      genes, respectively, opening prospects as an early detection tool.

PMID- 15514111
TI  - Acinetobacter sp. ADP1: an ideal model organism for genetic analysis and genome
      engineering.
AB  - Acinetobacter sp. strain ADP1 is a naturally transformable gram-negative
      bacterium with simple culture requirements, a prototrophic metabolism and a
      compact genome of 3.7 Mb which has recently been sequenced. Wild-type ADP1 can be
      genetically manipulated by the direct addition of linear DNA constructs to log
      phase cultures. This makes it an ideal organism for the automation of complex
      strain construction. Here, we demonstrate the flexibility and versatility of ADP1
      as a genetic model through the construction of a broad variety of mutants. These
      include marked and unmarked insertions and deletions, complementary replacements,
      chromosomal expression tags and complex combinations thereof. In the process of
      these constructions, we demonstrate that ADP1 can effectively express a wide
      variety of foreign genes including antibiotic resistance cassettes, essential
      metabolic genes, negatively selectable catabolic genes and even intact operons
      from highly divergent bacteria. All of the described mutations were achieved by
      the same process of splicing PCR, direct transformation of growing cultures and
      plating on selective media. The simplicity of these tools make genetic analysis
      and engineering with Acinetobacter ADP1 accessible to laboratories with minimal
      microbial genetics expertise and very little equipment. They are also compatible
      with complete automation of genetic analysis and engineering protocols.

PMID- 15514110
TI  - Unique features revealed by the genome sequence of Acinetobacter sp. ADP1, a
      versatile and naturally transformation competent bacterium.
AB  - Acinetobacter sp. strain ADP1 is a nutritionally versatile soil bacterium closely
      related to representatives of the well-characterized Pseudomonas aeruginosa and
      Pseudomonas putida. Unlike these bacteria, the Acinetobacter ADP1 is highly
      competent for natural transformation which affords extraordinary convenience for
      genetic manipulation. The circular chromosome of the Acinetobacter ADP1,
      presented here, encodes 3325 predicted coding sequences, of which 60% have been
      classified based on sequence similarity to other documented proteins. The close
      evolutionary proximity of Acinetobacter and Pseudomonas species, as judged by the
      sequences of their 16S RNA genes and by the highest level of bidirectional best
      hits, contrasts with the extensive divergence in the GC content of their DNA (40
      versus 62%). The chromosomes also differ significantly in size, with the
      Acinetobacter ADP1 chromosome <60% of the length of the Pseudomonas counterparts.
      Genome analysis of the Acinetobacter ADP1 revealed genes for metabolic pathways
      involved in utilization of a large variety of compounds. Almost all of these
      genes, with orthologs that are scattered in other species, are located in five
      major 'islands of catabolic diversity', now an apparent 'archipelago of catabolic
      diversity', within one-quarter of the overall genome. Acinetobacter ADP1 displays
      many features of other aerobic soil bacteria with metabolism oriented toward the
      degradation of organic compounds found in their natural habitat. A distinguishing
      feature of this genome is the absence of a gene corresponding to pyruvate kinase,
      the enzyme that generally catalyzes the terminal step in conversion of
      carbohydrates to pyruvate for respiration by the citric acid cycle. This finding
      supports the view that the cycle itself is centrally geared to the catabolic
      capabilities of this exceptionally versatile organism.

PMID- 15514113
TI  - Imbalanced plasminogen system in lymphangioleiomyomatosis: potential role of
      serum response factor.
AB  - Pulmonary lymphangioleiomyomatosis (LAM) is characterized by abnormal smooth
      muscle-like cell (LAM cell) proliferation leading to tissue destruction. We
      previously demonstrated that serum response factor (SRF), a critical smooth
      muscle transcription factor, is highly expressed in LAM cells. Here we show that
      a high SRF level alters the plasminogen (Plg) system. Specifically,
      overexpression of SRF in human lung fibroblasts upregulated urokinase-type
      plasminogen activator (uPA) and its substrate Plg, whereas it downregulated
      plasminogen activator inhibitor (PAI)-1. Because uPA cleaves Plg into plasmin,
      which activates matrix metalloproteinases (MMP), the end result was an increase
      in MMP activity. To determine whether uPA, Plg, and PAI-1 were abnormally
      expressed in LAM in vivo, we immunostained 12 LAM cases. In all cases, the LAM
      lesions showed stronger immunoreaction for uPA and Plg than the surrounding
      normal lung parenchyma. On the contrary, PAI-1 was absent in LAM lesions, whereas
      it was ubiquitous in normal lung parenchyma. Microdissection-based reverse
      transcriptase/polymerase chain reaction further confirmed upregulation of uPA and
      Plg and downregulation of PAI-1 message in LAM. Altogether, our findings suggest
      that the high SRF level seen in LAM contributes to extracellular matrix
      degradation and progressive LAM cell infiltration of the lung.

PMID- 15514112
TI  - Oxetane modified, conformationally constrained, antisense
      oligodeoxyribonucleotides function efficiently as gene silencing molecules.
AB  - Incorporation of nucleosides with novel base-constraining oxetane (OXE)
      modifications [oxetane, 1-(1',3'-O-anhydro-beta-d-psicofuranosyl nucleosides)]
      into antisense (AS) oligodeoxyribonucleotides (ODNs) should greatly improve the
      gene silencing efficiency of these molecules. This is because OXE modified bases
      provide nuclease protection to the natural backbone ODNs, can impart T(m) values
      similar to those predicted for RNA-RNA hybrids, and not only permit but also
      accelerate RNase H mediated catalytic activity. We tested this assumption in
      living cells by directly comparing the ability of OXE and phosphorothioate (PS)
      ODNs to target c-myb gene expression. The ODNs were targeted to two different
      sites within the c-myb mRNA. One site was chosen arbitrarily. The other was a
      'rational' choice based on predicted hybridization accessibility after physical
      mapping with self-quenching reporter molecules (SQRM). The Myb mRNA and protein
      levels were equally diminished by OXE and PS ODNs, but the latter were delivered
      to cells with approximately six times greater efficiency, suggesting that OXE
      modified ODNs were more potent on a molar basis. The rationally targeted
      molecules demonstrated greater silencing efficiency than those directed to an
      arbitrarily chosen mRNA sequence. We conclude that rationally targeted, OXE
      modified ODNs, can function efficiently as gene silencing agents, and hypothesize
      that they will prove useful for therapeutic purposes.

PMID- 15514114
TI  - The consequences of insulin-like growth factors/receptors dysfunction in lung
      cancer.
AB  - The aim of this study was to investigate the consequences of insulin-like growth
      factors (IGF) and IGF receptor dysfunction in lung carcinomas. A correlation
      between increased expression (at mRNA and protein levels) for IGF-1 and IGF-1R
      and decreased apoptosis were found in large-cell carcinomas and adenocarcinomas.
      In 40% of informative adenocarcinomas expressing the highest values of IGF-2 and
      Ki-67 proteins, M6P/IGF-2R gene had LOH at one allele and a mutation in another
      allele. All four squamous cell carcinoma samples expressed LOH/mutation in the
      M6P/IGF-2R gene. The alphaIR3 strongly diminished proliferation and increased
      apoptosis in cultures established from squamous cell carcinomas overexpressing
      IGF-2 and IGF-1R. Telomerase activity was assessed in four squamous cell
      carcinomas. Cell treatment with IGF-1 increased telomerase activity. The opposite
      was observed when the cells were treated with alphaIR3, which inhibits the
      activity of IGF-1 receptors. Our findings suggest that disruption of the IGF/IGF
      receptors axis is involved in lung cancer formation.

PMID- 15514115
TI  - Nuclear pore complex structure and dynamics revealed by cryoelectron tomography.
AB  - Nuclear pore complexes (NPCs) are gateways for nucleocytoplasmic exchange. To
      analyze their structure in a close-to-life state, we studied transport-active,
      intact nuclei from Dictyostelium discoideum by means of cryoelectron tomography.
      Subvolumes of the tomograms containing individual NPCs were extracted in silico
      and subjected to three-dimensional classification and averaging, whereby distinct
      structural states were observed. The central plug/transporter (CP/T) was variable
      in volume and could occupy different positions along the nucleocytoplasmic axis,
      which supports the notion that it essentially represents cargo in transit.
      Changes in the position of the CP/T were accompanied by structural rearrangements
      in the NPC scaffold.

PMID- 15514117
TI  - Probing electronic transitions in individual carbon nanotubes by Rayleigh
      scattering.
AB  - Rayleigh scattering spectra were obtained from individual single-walled carbon
      nanotubes with the use of a laser-generated visible and near-infrared
      supercontinuum. This diagnostic method is noninvasive and general for nanoscale
      objects. The approach permits clear identification of excited states in arbitrary
      metallic and semiconducting nanotubes. We analyzed spectral lineshapes in
      relation to the role of excitonic effects and correlated the results with Raman
      scattering data on individual tubes. The nanotube structure remained the same
      over distances of tens of micrometers. Small nanotube bundles retained distinct
      Rayleigh spectroscopic signatures of their component nanotubes, thus allowing the
      probing of nanotube-nanotube interactions.

PMID- 15514116
TI  - Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing
      its internalization.
AB  - Hepcidin is a peptide hormone secreted by the liver in response to iron loading
      and inflammation. Decreased hepcidin leads to tissue iron overload, whereas
      hepcidin overproduction leads to hypoferremia and the anemia of inflammation.
      Ferroportin is an iron exporter present on the surface of absorptive enterocytes,
      macrophages, hepatocytes, and placental cells. Here we report that hepcidin bound
      to ferroportin in tissue culture cells. After binding, ferroportin was
      internalized and degraded, leading to decreased export of cellular iron. The
      posttranslational regulation of ferroportin by hepcidin may thus complete a
      homeostatic loop: Iron regulates the secretion of hepcidin, which in turn
      controls the concentration of ferroportin on the cell surface.

PMID- 15514118
TI  - Detection of methane in the atmosphere of Mars.
AB  - We report a detection of methane in the martian atmosphere by the Planetary
      Fourier Spectrometer onboard the Mars Express spacecraft. The global average
      methane mixing ratio is found to be 10 +/- 5 parts per billion by volume (ppbv).
      However, the mixing ratio varies between 0 and 30 ppbv over the planet. The
      source of methane could be either biogenic or nonbiogenic, including past or
      present subsurface microorganisms, hydrothermal activity, or cometary impacts.

PMID- 15514119
TI  - High-energy physics. Accident shuts down SLAC, spurs probe of safety rules.

PMID- 15514120
TI  - Paleoanthropology. New species of small human found in Indonesia.

PMID- 15514121
TI  - Medicine. A wily recruiter in the battle against toxic beta amyloid aggregation.

PMID- 15514123
TI  - Physics. Fundamental constants appear constant--at least recently.

PMID- 15514122
TI  - Neuroscience. Prozac treatment of newborn mice raises anxiety.

PMID- 15514124
TI  - Diabetes research. Broad-Novartis venture promises a no-strings, public gene
      database.

PMID- 15514125
TI  - Developmental biology. Worm's light-sensing proteins suggest eye's single origin.

PMID- 15514126
TI  - European Research Council. Only the details are devilish for new funding agency.

PMID- 15514128
TI  - Science of elections. Gambling with our votes?

PMID- 15514127
TI  - International treaties. United Nations tackles cloning question--again.

PMID- 15514130
TI  - Plant ecology. Measuring the significance of a scientist's touch.

PMID- 15514129
TI  - Science of elections. How strategists design the perfect candidate.

PMID- 15514131
TI  - Polar science. China takes bold steps into Antarctic's forbidding interior.

PMID- 15514132
TI  - Susan Herring profile. Getting inside your head.

PMID- 15514133
TI  - Thermoelectrics. Temperature rises for devices that turn heat into electricity.

PMID- 15514134
TI  - Budget cuts affecting natural history.

PMID- 15514135
TI  - Tuition costs and funding needy students.

PMID- 15514136
TI  - Controversies over tuition increases.

PMID- 15514137
TI  - Sensitive versus classified information.

PMID- 15514138
TI  - Selection for asymmetry.

PMID- 15514139
TI  - Microbial diversity in archived soils.

PMID- 15514140
TI  - Comment on "Transmembrane segments of syntaxin line the fusion pore of Ca2+
      triggered exocytosis".

PMID- 15514142
TI  - Climate policy. An effective approach to climate change.

PMID- 15514143
TI  - Geophysics. Changing views on Earth's deep mantle.

PMID- 15514144
TI  - Biochemistry. How active sites communicate in thiamine enzymes.

PMID- 15514145
TI  - Chemistry. Polymorphism in liquids.

PMID- 15514146
TI  - Physics. Ancient lessons for our future climate.

PMID- 15514147
TI  - Plant biology. Plant acupuncture: sticking PINs in the right places.

PMID- 15514148
TI  - Symmetry breaking and the evolution of development.
AB  - Because of its simplicity, the binary-switch nature of left-right asymmetry
      permits meaningful comparisons among many different organisms. Phylogenetic
      analyses of asymmetry variation, inheritance, and molecular mechanisms reveal
      unexpected insights into how development evolves. First, directional asymmetry,
      an evolutionary novelty, arose from nonheritable origins almost as often as from
      mutations, implying that genetic assimilation ("phenotype precedes genotype") is
      a common mode of evolution. Second, the molecular pathway directing hearts
      leftward-the nodal cascade-varies considerably among vertebrates (homology of
      form does not require homology of development) and was possibly co-opted from a
      preexisting asymmetrical chordate organ system. Finally, declining frequencies of
      spontaneous asymmetry reversal throughout vertebrate evolution suggest that heart
      development has become more canalized.

PMID- 15514149
TI  - Partner-specific odor recognition in an Antarctic seabird.
AB  - Among birds, the Procellariiform seabirds (petrels, albatrosses, and shearwaters)
      are prime candidates for using chemical cues for individual recognition. These
      birds have an excellent olfactory sense, and a variety of species nest in burrows
      that they can recognize by smell. However, the nature of the olfactory signature-
      the scent that makes one burrow smell more like home than another--has not been
      established for any species. Here, we explore the use of intraspecific chemical
      cues in burrow recognition and present evidence for partner-specific odor
      recognition in a bird.

PMID- 15514150
TI  - Critical-like phenomena associated with liquid-liquid transition in a molecular
      liquid.
AB  - Contrary to the conventional wisdom that there is only one unique liquid state
      for any material, recent evidence suggests that there can be more than two liquid
      states even for a single-component substance. The transition between these liquid
      states is called a liquid-liquid phase transition. We report the detailed
      experimental investigation on the kinetics of the continuous spinodal
      decomposition-type transformation of one liquid into another for triphenyl
      phosphite. From the analysis of the linear regime, we found that the correlation
      length, xi, of fluctuations of the relevant order parameter diverges as xi =
      xi(0)[(T(SD) - T)/T(SD)](-nu) (where xi(0) = 60 nm and nu = 0.5) while
      approaching the spinodal temperature, T(SD). This is an indication of a critical
      like anomaly associated with the liquid-liquid transition. We also revealed that
      the order parameter governing the liquid-liquid transition must be of a
      nonconserved nature.

PMID- 15514151
TI  - Macroscopic separation of dense fluid phase and liquid phase of phosphorus.
AB  - Structural transformation between a dense molecular fluid and a polymeric liquid
      of phosphorus that occurred at about 1 gigapascal and 1000 degrees C was
      investigated by in situ x-ray radiography. When the low-pressure fluid was
      compressed, dark and round objects appeared in the radiograph. X-ray diffraction
      measurements confirmed that these objects were the highpressure liquid. The drops
      grew and eventually filled the sample space. Decompressing caused the reverse
      process. The macroscopic phase separation supported the existence of a first
      order phase transition between two stable disordered phases besides the liquid
      gas transition. X-ray absorption measurements revealed that the change in density
      at the transition corresponds to about 40% of the density of the high-pressure
      liquid.

PMID- 15514152
TI  - Energetics of hydrogen bond network rearrangements in liquid water.
AB  - A strong temperature dependence of oxygen K-edge x-ray absorption fine structure
      features was observed for supercooled and normal liquid water droplets prepared
      from the breakup of a liquid microjet. Analysis of the data over the temperature
      range 251 to 288 kelvin (-22 degrees to +15 degrees C) yields a value of 1.5 +/-
      0.5 kilocalories per mole for the average thermal energy required to effect an
      observable rearrangement between the fully coordinated ("ice-like") and distorted
      ("broken-donor") local hydrogen-bonding configurations responsible for the pre
      edge and post-edge features, respectively. This energy equals the latent heat of
      melting of ice with hexagonal symmetry (ice Ih) and is consistent with the
      distribution of hydrogen bond strengths obtained for the "overstructured" ST2
      model of water.

PMID- 15514153
TI  - Probabilistic tomography maps chemical heterogeneities throughout the lower
      mantle.
AB  - We obtained likelihoods in the lower mantle for long-wavelength models of bulk
      sound and shear wave speed, density, and boundary topography, compatible with
      gravity constraints, from normal mode splitting functions and surface wave data.
      Taking into account the large uncertainties in Earth's thermodynamic reference
      state and the published range of mineral physics data, we converted the
      tomographic likelihoods into probability density functions for temperature,
      perovskite, and iron variations. Temperature and composition can be separated,
      showing that chemical variations contribute to the overall buoyancy and are
      dominant in the lower 1000 kilometers of the mantle.

PMID- 15514154
TI  - Runcaria, a middle devonian seed plant precursor.
AB  - The emergence of the seed habit in the Middle Paleozoic was a decisive
      evolutionary breakthrough. Today, seed plants are the most successful plant
      lineage, with more than 250,000 living species. We have identified a middle
      Givetian (385 million years ago) seed precursor from Belgium predating the
      earliest seeds by about 20 million years. Runcaria is a small, radially
      symmetrical, integumented megasporangium surrounded by a cupule. The
      megasporangium bears an unopened distal extension protruding above the multilobed
      integument. This extension is assumed to be involved in anemophilous pollination.
      Runcaria sheds new light on the sequence of character acquisition leading to the
      seed.

PMID- 15514155
TI  - The evolutionary origin of cooperators and defectors.
AB  - Coexistence of cooperators and defectors is common in nature, yet the
      evolutionary origin of such social diversification is unclear. Many models have
      been studied on the basis of the assumption that benefits of cooperative acts
      only accrue to others. Here, we analyze the continuous snowdrift game, in which
      cooperative investments are costly but yield benefits to others as well as to the
      cooperator. Adaptive dynamics of investment levels often result in evolutionary
      diversification from initially uniform populations to a stable state in which
      cooperators making large investments coexist with defectors who invest very
      little. Thus, when individuals benefit from their own actions, large asymmetries
      in cooperative investments can evolve.

PMID- 15514156
TI  - A PINOID-dependent binary switch in apical-basal PIN polar targeting directs
      auxin efflux.
AB  - Polar transport-dependent local accumulation of auxin provides positional cues
      for multiple plant patterning processes. This directional auxin flow depends on
      the polar subcellular localization of the PIN auxin efflux regulators.
      Overexpression of the PINOID protein kinase induces a basal-to-apical shift in
      PIN localization, resulting in the loss of auxin gradients and strong defects in
      embryo and seedling roots. Conversely, pid loss of function induces an apical-to
      basal shift in PIN1 polar targeting at the inflorescence apex, accompanied by
      defective organogenesis. Our results show that a PINOID-dependent binary switch
      controls PIN polarity and mediates changes in auxin flow to create local
      gradients for patterning processes.

PMID- 15514157
TI  - Harnessing chaperones to generate small-molecule inhibitors of amyloid beta
      aggregation.
AB  - Protein aggregation is involved in the pathogenesis of neurodegenerative diseases
      and hence is considered an attractive target for therapeutic intervention.
      However, protein-protein interactions are exceedingly difficult to inhibit. Small
      molecules lack sufficient steric bulk to prevent interactions between large
      peptide surfaces. To yield potent inhibitors of beta-amyloid (Abeta) aggregation,
      we synthesized small molecules that increase their steric bulk by binding to
      chaperones but also have a moiety available for interaction with Abeta. This
      strategy yields potent inhibitors of Abeta aggregation and could lead to
      therapeutics for Alzheimer's disease and other forms of neurodegeneration.

PMID- 15514158
TI  - Ciliary photoreceptors with a vertebrate-type opsin in an invertebrate brain.
AB  - For vision, insect and vertebrate eyes use rhabdomeric and ciliary photoreceptor
      cells, respectively. These cells show distinct architecture and transduce the
      light signal by different phototransductory cascades. In the marine rag-worm
      Platynereis, we find both cell types: rhabdomeric photoreceptor cells in the eyes
      and ciliary photoreceptor cells in the brain. The latter use a photopigment
      closely related to vertebrate rod and cone opsins. Comparative analysis indicates
      that both types of photoreceptors, with distinct opsins, coexisted in
      Urbilateria, the last common ancestor of insects and vertebrates, and sheds new
      light on vertebrate eye evolution.

PMID- 15514159
TI  - A molecular switch and proton wire synchronize the active sites in thiamine
      enzymes.
AB  - Thiamine diphosphate (ThDP) is used as a cofactor in many key metabolic enzymes.
      We present evidence that the ThDPs in the two active sites of the E1 (EC 1.2.4.1)
      component of the pyruvate dehydrogenase complex communicate over a distance of 20
      angstroms by reversibly shuttling a proton through an acidic tunnel in the
      protein. This "proton wire" permits the co-factors to serve reciprocally as
      general acid/base in catalysis and to switch the conformation of crucial active
      site peptide loops. This synchronizes the progression of chemical events and can
      account for the oligomeric organization, conformational asymmetry, and "ping
      pong" kinetic properties of E1 and other thiamine-dependent enzymes.

PMID- 15514160
TI  - Early-life blockade of the 5-HT transporter alters emotional behavior in adult
      mice.
AB  - Reduced serotonin transporter (5-HTT) expression is associated with abnormal
      affective and anxiety-like symptoms in humans and rodents, but the mechanism of
      this effect is unknown. Transient inhibition of 5-HTT during early development
      with fluoxetine, a commonly used serotonin selective reuptake inhibitor, produced
      abnormal emotional behaviors in adult mice. This effect mimicked the behavioral
      phenotype of mice genetically deficient in 5-HTT expression. These findings
      indicate a critical role of serotonin in the maturation of brain systems that
      modulate emotional function in the adult and suggest a developmental mechanism to
      explain how low-expressing 5-HTT promoter alleles increase vulnerability to
      psychiatric disorders.

PMID- 15514161
TI  - Protein kinase C overactivity impairs prefrontal cortical regulation of working
      memory.
AB  - The prefrontal cortex is a higher brain region that regulates thought, behavior,
      and emotion using representational knowledge, operations often referred to as
      working memory. We tested the influence of protein kinase C (PKC) intracellular
      signaling on prefrontal cortical cognitive function and showed that high levels
      of PKC activity in prefrontal cortex, as seen for example during stress exposure,
      markedly impair behavioral and electrophysiological measures of working memory.
      These data suggest that excessive PKC activation can disrupt prefrontal cortical
      regulation of behavior and thought, possibly contributing to signs of prefrontal
      cortical dysfunction such as distractibility, impaired judgment, impulsivity, and
      thought disorder.

PMID- 15514162
TI  - A centrosomal localization signal in cyclin E required for Cdk2-independent S
      phase entry.
AB  - Excess cyclin E-Cdk2 accelerates entry into S phase of the cell cycle and
      promotes polyploidy, which may contribute to genomic instability in cancer cells.
      We identified 20 amino acids in cyclin E as a centrosomal localization signal
      (CLS) essential for both centrosomal targeting and promoting DNA synthesis.
      Expressed wild-type, but not mutant, CLS peptides localized on the centrosome,
      prevented endogenous cyclin E and cyclin A from localizing to the centrosome, and
      inhibited DNA synthesis. Ectopic cyclin E localized to the centrosome and
      accelerated S phase entry even with mutations that abolish Cdk2 binding, but not
      with a mutation in the CLS. These results suggest that cyclin E has a modular
      centrosomal-targeting domain essential for promoting S phase entry in a Cdk2
      independent manner.

PMID- 15514163
TI  - Protein kinase D is a novel mediator of cardiac troponin I phosphorylation and
      regulates myofilament function.
AB  - Protein kinase D (PKD) is a serine kinase whose myocardial substrates are
      unknown. Yeast 2-hybrid screening of a human cardiac library, using the PKD
      catalytic domain as bait, identified cardiac troponin I (cTnI), myosin-binding
      protein C (cMyBP-C), and telethonin as PKD-interacting proteins. In vitro
      phosphorylation assays revealed PKD-mediated phosphorylation of cTnI, cMyBP-C,
      and telethonin, as well as myomesin. Peptide mass fingerprint analysis of cTnI by
      liquid chromatography-coupled mass spectrometry indicated PKD-mediated
      phosphorylation of a peptide containing Ser22 and Ser23, the protein kinase A
      (PKA) targets. Ser22 and Ser23 were replaced by Ala, either singly (Ser22Ala or
      Ser23Ala) or jointly (Ser22/23Ala), and the troponin complex reconstituted in
      vitro, using wild-type or mutated cTnI together with wild-type cardiac troponin C
      and troponin T. PKD-mediated cTnI phosphorylation was reduced in complexes
      containing Ser22Ala or Ser23Ala cTnI and completely abolished in the complex
      containing Ser22/23Ala cTnI, indicating that Ser22 and Ser23 are both targeted by
      PKD. Furthermore, troponin complex containing wild-type cTnI was phosphorylated
      with similar kinetics and stoichiometry (approximately 2 mol phosphate/mol cTnI)
      by both PKD and PKA. To determine the functional impact of PKD-mediated
      phosphorylation, Ca2+ sensitivity of tension development was studied in a rat
      skinned ventricular myocyte preparation. PKD-mediated phosphorylation did not
      affect maximal tension but produced a significant rightward shift of the tension
      pCa relationship, indicating reduced myofilament Ca2+ sensitivity. At submaximal
      Ca2+ activation, PKD-mediated phosphorylation also accelerated isometric
      crossbridge cycling kinetics. Our data suggest that PKD is a novel mediator of
      cTnI phosphorylation at the PKA sites and may contribute to the regulation of
      myofilament function.

PMID- 15514164
TI  - RNA-binding proteins heterogeneous nuclear ribonucleoprotein A1, E1, and K are
      involved in post-transcriptional control of collagen I and III synthesis.
AB  - Collagen types I and III, coded by COL1A1/COL1A2 and COL3A1 genes, are the major
      fibrillar collagens produced by fibroblasts, including cardiac fibroblasts of the
      adult heart. Characteristic for different cardiomyopathies is a remodeling
      process associated with an upregulation of collagen synthesis, which leads to
      fibrosis. We report identification of three mRNA-binding proteins, heterogeneous
      nuclear ribonucleoprote (hnRNP) A1, E1, and K, as positive effectors of collagen
      synthesis acting at the post-transcriptional level by interaction with the 3'
      untranslated regions (3'-UTRs) of COL1A1, 1A2, and 3A1 mRNAs. In vitro, binding
      experiments (electromobility shift assay and UV cross-linking) reveal significant
      differences in binding to CU- and AU-rich binding motifs. Reporter gene cell
      transfection experiments and RNA stability assays show that hnRNPs A1, E1, and K
      stimulate collagen expression by stabilizing mRNAs. Collagen synthesis is
      activated via the angiotensin II type 1 (AT1) receptor. We demonstrate that
      transforming growth factor-beta1, a major product of stimulated AT1 receptor,
      does not activate solely collagen synthesis but synergistically the synthesis of
      hnRNP A1, E1, and K as well. Thus, post-transcriptional control of collagen
      synthesis at the mRNA level may substantially be caused by alteration of the
      expression of RNA-binding proteins. The pathophysiological impact of this finding
      was demonstrated by screening the expression of hnRNP E1 and K in cardiovascular
      diseases. In the heart muscle of patients experiencing aortic stenosis, ischemic
      cardiomyopathy, or dilatative cardiomyopathy, a significant increase in the
      expression of hnRNP E1, A1, and K was found between 1.5- and 4.5-fold relative to
      controls.

PMID- 15514165
TI  - Blood pressure control goes nuclear.

PMID- 15514166
TI  - Cardiac regeneration: self-service at the pump.

PMID- 15514167
TI  - Chemokines in the pathogenesis of vascular disease.
AB  - Our increasing appreciation of the importance of inflammation in vascular disease
      has focused attention on the molecules that direct the migration of leukocytes
      from the blood stream to the vessel wall. In this review, we summarize roles of
      the chemokines, a family of small secreted proteins that selectively recruit
      monocytes, neutrophils, and lymphocytes to sites of vascular injury,
      inflammation, and developing atherosclerosis. Chemokines induce chemotaxis
      through the activation of G-protein-coupled receptors, and the receptors that a
      given leukocyte expresses determines the chemokines to which it will respond.
      Monocyte chemoattractant protein 1 (MCP-1), acting through its receptor CCR2,
      appears to play an early and important role in the recruitment of monocytes to
      atherosclerotic lesions and in the formation of intimal hyperplasia after
      arterial injury. Acute thrombosis is an often fatal complication of
      atherosclerotic plaque rupture, and recent evidence suggests that MCP-1
      contributes to thrombin generation and thrombus formation by generating tissue
      factor. Because of their critical roles in monocyte recruitment in vascular and
      nonvascular diseases, MCP-1 and CCR2 have become important therapeutic targets,
      and efforts are underway to develop potent and specific antagonists of these and
      related chemokines.

PMID- 15514168
TI  - Cyclin-dependent kinase-9: an RNAPII kinase at the nexus of cardiac growth and
      death cascades.
AB  - Over the past decade and a half, the paradigm has emerged of cardiac hypertrophy
      and ensuing heart failure as fundamentally a problem in signal transduction,
      impinging on the altered expression or function of gene-specific transcription
      factors and their partners, which then execute the hypertrophic phenotype.
      Strikingly, RNA polymerase II (RNAPII) is itself a substrate for two protein
      kinases-the cyclin-dependent kinases Cdk7 and Cdk9--that are activated by
      hypertrophic cues. Phosphorylation of RNAPII in the carboxyl terminal domain
      (CTD) of its largest subunit controls a number of critical steps subsequent to
      transcription initiation, among them enabling RNAPII to overcome its stalling in
      the promoter-proximal region and to engage in efficient transcription elongation.
      Here, we summarize our current understanding of the RNAPII-directed protein
      kinases in cardiac hypertrophy. Cdk9 activation is essential in tissue culture
      for myocyte enlargement and sufficient in transgenic mice for hypertrophy to
      occur and yet is unrelated to the "fetal" gene program that is typical of
      pathophysiological heart growth. Although this trophic effect of Cdk9 appears
      benign superficially, pathophysiological levels of Cdk9 activity render
      myocardium remarkably susceptible to apoptotic stress. Cdk9 interacts adversely
      with Gq-dependent pathways for hypertrophy, impairing the expression of numerous
      genes for mitochondrial proteins, and, in particular, suppressing master
      regulators of mitochondrial biogenesis and function, perioxisome proliferator
      activated receptor-gamma coactivator-1 (PGC-1), and nuclear respiratory factor-1
      (NRF-1). Given the dual transcriptional roles of Cdk9 in hypertrophic growth and
      mitochondrial dysfunction, we suggest the potential usefulness of Cdk9 as a
      target in heart failure drug discovery.

PMID- 15514169
TI  - Alcohol consumption and carotid artery structure in older French adults: the
      Three-City Study.
AB  - BACKGROUND AND PURPOSE: Several epidemiological studies have suggested a U-shaped
      association between alcohol consumption and cardiovascular risk. However, the
      modifications of vascular structure associated with alcohol consumption are
      largely unknown. METHODS: The study population sample comprised 6216 subjects
      (3780 women and 2436 men) aged 65 years or older who were recruited from 3 French
      cities (Bordeaux, Dijon, and Montpellier, which are located in the 3 principal
      wine-growing regions). Usual alcohol consumption was assessed by a standardized
      questionnaire. Carotid ultrasound examination included measurements (at sites
      free of plaques) of intima-media thickness (IMT) at the common carotid arteries
      (CCA), CCA-lumen diameter, and assessment of atherosclerotic plaques in the
      extracranial carotid arteries. RESULTS: Neither CCA-IMT nor carotid plaques were
      associated with alcohol consumption categories in the overall population. Weak
      and marginal positive associations were observed between categories of alcohol
      consumption and carotid plaques in men (P=0.02 for linear trend). CCA-lumen
      diameter was positively and independently associated with alcohol consumption in
      overall population and in men and in women. Similar results were found between
      alcohol consumption and carotid measurements in subjects free of cardiovascular
      disease (90.1% of the population). CONCLUSIONS: This very large population sample
      of French older adults shows no marked relationships of alcohol consumption with
      atherosclerosis. The positive association of alcohol intake with carotid arterial
      diameter may reflect the ability of alcohol to maintain adaptive enlargement to
      preserve lumen area.

PMID- 15514170
TI  - In-hospital initiation of secondary stroke prevention therapies yields high rates
      of adherence at follow-up.
AB  - BACKGROUND AND PURPOSE: The Stroke PROTECT (Preventing Recurrence Of
      Thromboembolic Events through Coordinated Treatment) program systematically
      implements, at the time of acute transient ischemic attack (TIA) or ischemic
      stroke admission, 8 medication/behavioral secondary prevention measures known to
      improve outcome in patients with cerebrovascular disease. The objective of this
      study was to determine if the high utilization rates previously demonstrated at
      hospital discharge were maintained at 90 days after discharge. METHODS: Data were
      prospectively collected on consecutively encountered ischemic stroke and TIA
      patients admitted to a university hospital stroke service beginning September 1,
      2002. PROTECT interventions were initiated before hospital discharge in all
      PROTECT-target (underlying stroke mechanism large vessel atherosclerosis or small
      vessel disease) and PROTECT-ACS (At-risk for Coronary Sequelae) patients.
      Adherence to program goals was assessed 3 months after discharge. RESULTS: During
      the period from September 2002 to August 2003, 144 individuals met criteria for
      PROTECT intervention. Of the 130 patients (90%) with available day 90 follow-up
      data, mean age was 72 (range, 37 to 95), and 63% were male. Adherence rates in
      patients without specific contraindications were 100% for antithrombotics, 99%
      for statins, 92% for angiotensin-converting enzyme inhibitors/angiotensin
      receptor blockers, and 80% for thiazides. Awareness of the importance of calling
      911 in response to stroke was 87%. Adherence to diet and exercise guidelines were
      78% and 70%, respectively. Of the 24 smokers, tobacco cessation was maintained in
      20 (83%). CONCLUSIONS: High rates of adherence to PROTECT therapies were
      maintained at 90 days after hospital discharge.

PMID- 15514171
TI  - MERCI 1: a phase 1 study of Mechanical Embolus Removal in Cerebral Ischemia.
AB  - BACKGROUND AND PURPOSE: To report the result of the Mechanical Embolus Removal in
      Cerebral Ischemia (MERCI) 1 study, a phase 1 trial to evaluate the safety and
      efficacy of mechanical embolectomy in the cerebral vasculature. METHODS: MERCI 1
      enrolled 30 patients in 7 US centers. Main inclusion criteria were: National
      Institutes of Health Stroke Scale score (NIHSS) > or =10; treatment performed
      within 8 hours from symptoms onset and contra-indication to intravenous
      thrombolysis; no large hypodensity on computed tomography; and occlusion of a
      major cerebral artery on the angiogram. Safety was defined by the absence of
      vascular injury or symptomatic intracranial hemorrhage. Efficacy was assessed by
      recanalization rate and clinical outcome at 1 month. Significant recovery was
      defined as 30-day modified Rankin of 0 to 2 in patients with baseline NIHSS 10 to
      20 and 30-day modified Rankin of 0 to 3 in patients with baseline NIHSS >20. The
      procedures were performed with the Merci Retrieval System, a system specially
      designed for intracranial embolectomy. RESULTS: Twenty-eight patients were
      treated. Median NIHSS was 22. Median time from onset to completion of treatment
      was 6 hours and 15 minutes. Successful recanalization with mechanical embolectomy
      only was achieved in 12 (43%) patients, and with additional intra-arterial tissue
      plasminogen activator in 18 (64%) patients. There was one procedure related
      technical complication, with no clinical consequence. Twelve asymptomatic and no
      symptomatic intracranial hemorrhages occurred. At 1 month, 9 of 8 revascularized
      patients and 0 of 10 nonrevascularized patients had achieved significant
      recovery. CONCLUSIONS: This phase 1 study shows that cerebral embolectomy with
      the Merci Retriever was safe and that successful recanalization could benefit a
      significant number of patients, even when performed in an extended 8-hour time
      window.

PMID- 15514172
TI  - Body mass index in mid-life is associated with a first stroke in men: a
      prospective population study over 28 years.
AB  - BACKGROUND AND PURPOSE: Data on the association between obesity and stroke are
      still limited. We examined the possible association between mid-life body mass
      index (BMI) and risk of stroke in the prospective Multifactor Primary Prevention
      Study in Goteborg, Sweden. METHODS: 7402 apparently healthy men aged 47 to 55 at
      baseline were followed-up over a 28-year period. Incidence of fatal and nonfatal
      stroke was recorded in a local stroke registry through the Swedish National
      Register on Cause of Death and the Swedish Hospital Discharge Registry. RESULTS:
      A total of 873 first strokes were recorded, including 495 ischemic, 144
      hemorrhagic, and 234 unspecified strokes. Compared with men with low normal
      weight (BMI, 20.0 to 22.49 kg/m2), men with BMI >30.0 kg/m2 had a multiple
      adjusted hazard ratio of 1.93 (95% CI, 1.44 to 2.58) for total stroke, 1.78 (95%
      CI, 1.22 to 2.60) for ischemic stroke, and 3.91 (95% CI, 2.10 to 7.27) for
      unspecified stroke. There was no significant association between BMI and
      hemorrhagic stroke. Adjustment for potential mediators, eg, hypertension,
      diabetes and serum cholesterol levels, attenuated but did not eliminate the risk.
      CONCLUSIONS: In this prospective population-based study of men, increased BMI in
      mid-life was associated with an increased risk for total, ischemic, and
      unspecified stroke, but not with hemorrhagic stroke. The result supports the role
      of mid-life BMI as a risk factor for stroke later in life and suggests a
      differentiated effect on stroke subtypes.

PMID- 15514173
TI  - Favorable early outcome of carotid artery stenting without protection devices.
AB  - BACKGROUND AND PURPOSE: Protection devices are increasingly used in carotid
      artery stenting. However, no randomized trial has been conducted to evaluate the
      efficacy of such devices, and arguments have also been formulated against their
      routine use. We set out to investigate the complication rates associated with
      carotid artery stenting performed without protection devices. Applicability of
      covered stents in the carotid system was also evaluated. METHODS: Between January
      2001 and July 2003, 245 consecutive patients (260 hemispheres) underwent carotid
      artery stenting. No protection devices were applied. Covered stents were
      implanted in 31 (12.1%) cases. The incidence of complications during the
      intervention and the subsequent 30-day follow-up period was recorded. RESULTS:
      The technical success rate was 98.8%. One postprocedural nonneurological death
      (0.4%) occurred. Neurological complications (inclusive of transient ischemic
      attacks) were observed in 14 cases (5.4%). The rate of major complications
      (death, major stroke, and myocardial infarction) was 1.6% among the symptomatic
      and 1.5% among the asymptomatic cases. The rate of minor strokes was 3.2% in the
      symptomatic and 1.5% in the asymptomatic group. Of the neurological
      complications, 64.3% occurred postprocedurally. No ipsilateral neurological
      complications were detected in the subgroup treated with covered stents.
      CONCLUSIONS: Carotid artery stenting without protection devices appears to be
      safe. Most of the neurological complications could not have been prevented with
      protection devices, because they occurred after the intervention. The application
      of covered stents may reduce the rate of embolization-related complications in
      the periprocedural period.

PMID- 15514174
TI  - Do normal D-dimer levels reliably exclude cerebral sinus thrombosis?
AB  - BACKGROUND AND PURPOSE: Cerebral sinus thrombosis (CST) needs to be considered in
      the differential diagnosis of all patients with acute headache. Early diagnosis
      is essential because early treatment may prevent morbidity and may even be life
      saving. Definite exclusion, however, needs advanced neuroradiologic diagnostics,
      which are not readily available in many hospitals. Because measurement of D
      dimers has been demonstrated to be helpful in excluding thromboembolic disease,
      our aim was to investigate whether D-dimers would be also sensitive enough to
      exclude CST. METHODS: We undertook a prospective multicenter study over a 2.5
      year period including all patients who came to the emergency departments with
      symptoms suggestive of CST. All patients were diagnosed either by magnetic
      resonance venography, spiral computed tomography scan venography, or intra
      arterial digital subtraction angiography. D-dimer levels were measured at
      admission and analyzed by the same method in all patients. RESULTS: A total of
      343 patients were included. CST was diagnosed in 35 patients, of whom 34 had D
      dimers above the cutoff value (>500 microg/L). From the 308 patients not having
      CST, D-dimers were elevated in 27. Sensitivity of D-dimers was 97.1%, with a
      negative predictive value of 99.6%. Specificity was 91.2%, with a positive
      predictive value of 55.7%. D-dimers were positively correlated with the extent of
      the thrombosis and negatively correlated with the duration of symptoms (Spearman
      rank correlation coefficients 0.76, -0.58, respectively). CONCLUSIONS: D-dimer
      measurement is useful in patients with suspected CST. Normal D-dimers make the
      presence of CST very unlikely.

PMID- 15514175
TI  - Microembolic signal predicts recurrent cerebral ischemic events in acute stroke
      patients with middle cerebral artery stenosis.
AB  - BACKGROUND AND PURPOSE: Cerebral embolism is a common cause of stroke.
      Microembolic signals (MES) detected by transcranial Doppler represent ongoing
      embolisms, but the lack of reliable data about its clinical relevance hinders its
      widespread use in clinical practice. METHODS: We prospectively monitored 114
      consecutive acute ischemic stroke patients with middle cerebral artery (MCA)
      stenosis for MES. The signals on digital audio tape were analyzed by an
      independent observer who was blinded to all other data. All patients were
      followed-up for the occurrence of recurrent stroke or transient ischemic attack
      (TIA) in the indexed MCA territory. RESULTS: MES was detected in 25 (22%)
      patients. The mean number of MES was 18 (range, 1 to 102). MES were more common
      in patients with severe stenosis (10/21, 48%) than in those with mild-moderate
      stenosis (4/26, 15%) (Pearson chi2 P=0.02). During follow-up for a mean of 13.6
      months (range, 1 to 32), 12 (12%) patients had further ischemic events (10
      strokes and 2 TIAs) in the affected MCA region during follow-up. Among these, 7
      (58%) had recurred within 1 month (1 recurred within 1 week, the other 6 patients
      had recurrences in week 3 or 4 after discharge), 3 within 6 months, 1 within 6 to
      12 months, and the remaining 1 recurred after 1 year. The presence of MES was the
      only predictor of a further ischemic stroke/TIA by Cox regression (adjusted odds
      ratio, 8.45; 95% CI, 1.69 to 42.22; P=0.01) even after controlling for age, sex,
      diabetes, hypertension, previous stroke, smoking, and acute treatment.
      CONCLUSIONS: In acute stroke patients with MCA stenosis, MES predicts further
      cerebral ischemia. This procedure should be considered as part of routine
      investigation and might identify a group of patients who are most likely to
      benefit from antithrombotic treatment.

PMID- 15514180
TI  - Statins in stroke prevention and carotid atherosclerosis: systematic review and
      up-to-date meta-analysis.
AB  - BACKGROUND AND PURPOSE: Previously published meta-analyses exploring the effect
      of statins on stroke incidence included 20,000 patients and found a 2% to 30%
      risk reduction. It is not clear whether this is attributable to low-density
      lipoprotein-cholesterol (LDL-C) reduction. Statin trials have now included
      >90,000 patients. We have determined the effect of statins and LDL-C reduction on
      stroke prevention. SUMMARY OF REVIEW: We performed a systematic review and meta
      analysis of all randomized trials testing statin drugs published before August
      2003. The trials were identified using a computerized PubMed search. We analyzed
      separately statin effect on incident strokes and on carotid intima-media
      thickness (IMT) according to LDL-C reduction. The relative risk reduction for
      stroke was 21% (odds ratio [OR], 0.79 [0.73 to 0.85]), with no heterogeneity
      between trials. Fatal strokes were reduced but not significantly: by 9% (OR, 0.91
      [0.76 to 1.10]). There was no increase in hemorrhagic strokes (OR, 0.90 [0.65 to
      1.22]). Statin size effect was closely associated with LDL-C reduction. Each 10%
      reduction in LDL-C was estimated to reduce the risk of all strokes by 15.6% (95%
      CI, 6.7 to 23.6) and carotid IMT by 0.73% per year (95% CI, 0.27 to 1.19).
      CONCLUSIONS: Statins may reduce the incidence of all strokes without any increase
      in hemorrhagic strokes, and this effect is mainly driven by the extent of between
      group LDL-C reduction. Carotid IMT progression also strongly correlated with LDL
      C reduction.

PMID- 15514182
TI  - Intravenous administration of a GPIIb/IIIa receptor antagonist extends the
      therapeutic window of intra-arterial tenecteplase-tissue plasminogen activator in
      a rat stroke model.
AB  - BACKGROUND AND PURPOSE: Occlusion of the middle cerebral artery triggers platelet
      accumulation at the site of occlusion and in downstream microvessels. The
      platelet-induced secondary thrombosis promotes the progressive development of
      ischemic brain damage and contributes to the resistance to thrombolysis and to
      the tight 3-hour therapeutic window. We tested the hypothesis that combination of
      intravenous (IV) administration of a GPIIb/IIIa receptor antagonist, 7E3 F(ab')2,
      with intra-arterial (IA) administration of tenecteplase-tissue plasminogen
      activator (TNK-tPA) increases the efficacy of thrombolysis and extends the
      therapeutic window of stroke. METHODS: Rats subjected to embolic stroke were
      treated with IV 7E3 F(ab')2 (6 mg/kg) in combination with IA or IV TNK-tPA (5
      mg/kg) at 4 and 6 hours after onset of stroke, respectively; IA TNK-tPA (5 mg/kg)
      alone at 6 hours after onset of stroke; or saline at 6 hours after onset of
      stroke. RESULTS: The combination of IV 7E3 F(ab')2 (4 hours) and IA TNK-tPA (6
      hours) significantly (P<0.05) reduced infarct volume and improved neurological
      functional deficits, which was associated with significant (P<0.05) reductions in
      the size of embolus at the origin of the occluded middle cerebral artery and in
      down-stream microvascular platelet and fibrin deposition, and enhanced
      microvascular patency compared with saline-treated rats. However, combination of
      IV 7E3 F(ab')2 (4 hours) and IV TNK-tPA (6 hours) or IA TNK-tPA (6 hours) alone
      failed to reduce infarct volume and improve neurological function compared with
      the saline-treated rats. No significant differences of the incidence of
      hemorrhage were detected among groups. CONCLUSIONS: These data suggest that the
      combination of IV 7E3 F(ab')2 (4 hours) and IA TNK-tPA (6 hours) extends the
      therapeutic window of thrombolysis to 6 hours after stroke.

PMID- 15514183
TI  - Effective prophylaxis for deep venous thrombosis after stroke: both low-dose
      anticoagulation and stockings for most cases.

PMID- 15514184
TI  - Effective prophylaxis for deep vein thrombosis after stroke: low-dose
      anticoagulation rather than stockings alone: against.

PMID- 15514185
TI  - Distribution and cross-sectional age-related increases of carotid artery intima
      media thickness in young adults: the Bogalusa Heart Study.
AB  - BACKGROUND AND PURPOSE: Reference values and age-related changes of carotid
      intima-media thickness (CIMT) have not been described in a community-based sample
      of young asymptomatic adults. CIMT measurements from the Bogalusa Heart Study, a
      study of the natural history of atherosclerosis in young adults and children,
      were used to characterize age-, race-, and sex-specific CIMT distributions and
      yearly rates of change. METHODS: Age-, sex-, and race-specific CIMT percentile
      values and cross-sectional changes with age were estimated using B-mode carotid
      ultrasound images from 519 young adults (mean age 32 years, 61% female, 29%
      black). Nomograms of CIMT percentiles between the ages of 25 and 40 years are
      provided in 5-year increments. RESULTS: CIMT was thickest in the carotid bulb and
      increased linearly with age, most rapidly in the bulb. With age, composite CIMT
      increased most slowly in white females and most rapidly in white males. Sample
      size estimates projected that 268 to 462 subjects are needed to detect CIMT
      changes > or =0.010 mm/year. CONCLUSIONS: These estimated CIMT distributions and
      percentiles can serve as reference values for assessment of subclinical
      atherosclerosis in young adults. The observed age-related differences in CIMT can
      be used to plan epidemiological and clinical trials investigating atherosclerosis
      and anti-atherosclerotic interventions.

PMID- 15514186
TI  - Multicenter randomized controlled trial of an outreach nursing support program
      for recently discharged stroke patients.
AB  - BACKGROUND AND PURPOSE: Many stroke patients and informal carers experience a
      decreased quality of life after discharge home and are dissatisfied with the care
      received. We assessed the effectiveness of an outreach nursing care program.
      METHODS: In a multicenter trial, 536 stroke patients were randomized at discharge
      to standard care (n=273) or standard care plus outreach care (n=263). The
      outreach care consisted of 3 telephone calls and 1 home visit within 5 months
      after discharge by 1 of 13 stroke nurses. Patients were masked for the trial
      objectives. Six months after discharge, they assessed the 2 primary outcomes:
      quality of life (Short Form 36 [SF-36]) and dissatisfaction with care. Secondary
      measures of outcome were disability, handicap, depression, anxiety, and use of
      health care services and secondary prevention drugs. Informal carers assessed
      strain, and social support. Analysis was by intention to treat. RESULTS: Twelve
      patients died before follow-up, 38 declined outcome assessment, and 486 completed
      the primary outcome assessments. Outreach care patients had better scores on the
      SF-36 domain "Role Emotional" than controls (mean difference 7.9 [95% confidence
      limit, 0.1 to 15.7]). No statistically significant differences were found on the
      other primary outcome measures. For secondary outcomes, no statistically
      significant differences were found, except that intervention patients used fewer
      rehabilitation services (relative risk, 0.66 [0.44 to 1.00]) and had lower
      anxiety scores (median difference 1 [0.19 to 2.79]). CONCLUSIONS: This outreach
      nursing stroke care was not effective in improving quality of life and
      dissatisfaction with care of recently discharged patients.

PMID- 15514187
TI  - Aspirin for stroke prevention taken in the evening?

PMID- 15514188
TI  - Surgery versus stenting: how medical device makers influence patient care.

PMID- 15514190
TI  - Which time-to-peak threshold best identifies penumbral flow? A comparison of
      perfusion-weighted magnetic resonance imaging and positron emission tomography in
      acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: In acute ischemic stroke, the hypoperfused but viable
      tissue is the main therapeutic target. In clinical routine, time-to-peak (TTP)
      maps are frequently used to estimate the hemodynamic compromise and to calculate
      the mismatch volume. We evaluated the accuracy of TTP maps to identify penumbral
      flow by comparison with positron emission tomography (PET). METHODS: Magnetic
      resonance imaging (MRI) and PET were performed in 11 patients with acute ischemic
      stroke (median 8 hours after stroke onset, 60 minutes between MRI and PET
      imaging). The volumes defined by increasing TTP thresholds (relative TTP delay of
      >2, >4, >6, >8, and >10 seconds) were compared with the volume of hypoperfusion
      (<20 mL/100 g per min) assessed by 15O-water PET. In a volumetric analysis, each
      threshold's sensitivity, specificity, and predictive values were calculated.
      RESULTS: The median hypoperfusion volume was 34.5 cm3. Low TTP thresholds
      included large parts of the hypoperfused but also large parts of normoperfused
      tissue (median sensitivity/specificity: 93%/60% for TTP >2) and vice versa
      (50%/91% for TTP >10). TTP >4 seconds best identifies hypoperfusion (84%/77%).
      The positive predictive values increased with the size of hypoperfusion.
      CONCLUSIONS: This first comparison of quantitative PET-CBF with TTP maps in acute
      ischemic human stroke indicates that the TTP threshold is crucial to reliably
      identify the tissue at risk; TTP >4 seconds best identifies penumbral flow; and
      TTP maps overestimate the extent of true hemodynamic compromise depending on the
      size of ischemia. Only if methodological restrictions are kept in mind, relative
      TTP maps are suitable to estimate the mismatch volume.

PMID- 15514191
TI  - Interaction between inducible nitric oxide synthase and poly(ADP-ribose)
      polymerase in focal ischemic brain injury.
AB  - BACKGROUND AND PURPOSE: Overactivation of the DNA repair enzyme poly(ADP-ribose)
      polymerase (PARP) contributes to ischemic brain injury. Because PARP upregulates
      proinflammatory genes, we investigated whether inducible nitric oxide synthase
      (iNOS), a gene involved in the deleterious effects of postischemic inflammation,
      participates in the mechanisms by which PARP activation contributes to cerebral
      ischemic injury. METHODS: The middle cerebral artery (MCA) was occluded in mice
      for 20 minutes using an intravascular filament, and injury volume was measured 72
      hours later in Nissl-stained brain sections. mRNA expression was assessed in the
      postischemic brain by the quantitative "real-time" polymerase chain reaction.
      RESULTS: The PARP inhibitor PJ34 reduced infarct volume and attenuated
      postischemic iNOS mRNA upregulation by 72%. To determine whether iNOS contributes
      to the toxicity of PARP, the iNOS inhibitor aminoguanidine was co-administered
      with PARP inhibitors. Unexpectedly, co-administration of PARP and iNOS
      inhibitors, or treatment of iNOS-null mice with PARP inhibitors, abrogated the
      protective effect afforded by iNOS or PARP inhibition alone. The loss of
      neuroprotection was associated with upregulation of the inflammatory genes iNOS,
      intercellular adhesion molecule-1, and gp91(phox). CONCLUSIONS: The results
      suggest that iNOS expression contributes to the deleterious effects exerted by
      PARP activation in cerebral ischemia. However, iNOS activity is required for the
      protective effect of PARP inhibition and, conversely, PARP activity must be
      present for iNOS inhibition to be effective. The findings unveil a previously
      unrecognized deleterious interaction between iNOS and PARP that is relevant to
      the development of combination therapies for ischemic stroke.

PMID- 15514192
TI  - Different effects of antihypertensive regimens based on fosinopril or
      hydrochlorothiazide with or without lipid lowering by pravastatin on progression
      of asymptomatic carotid atherosclerosis: principal results of PHYLLIS--a
      randomized double-blind trial.
AB  - BACKGROUND AND PURPOSE: The Plaque Hypertension Lipid-Lowering Italian Study
      (PHYLLIS) tested whether (1) the angiotensin-converting enzyme (ACE) inhibitor
      fosinopril (20 mg per day) was more effective on carotid atherosclerosis
      progression than the diuretic hydrochlorothiazide (25 mg per day), (2)
      pravastatin (40 mg per day) was more effective than placebo when added to either
      hydrochlorothiazide or fosinopril, and (3) there were additive effects of ACE
      inhibitor and lipid-lowering therapies. METHODS: A total of 508 hypertensive,
      hypercholesterolemic patients with asymptomatic carotid atherosclerosis were
      randomized to: (A) hydrochlorothiazide; (B) fosinopril; (C) hydrochlorothiazide
      plus pravastatin; and (D) fosinopril plus pravastatin, and followed up blindly
      for 2.6 years. B-Mode carotid scans were performed yearly by certified
      sonographers in 13 hospitals and read centrally. Corrections for drift were
      calculated from readings repeated at study end. Primary outcome was change in
      mean maximum intima-media thickness of far and near walls of common carotids and
      bifurcations bilaterally (CBM(max)). RESULTS: CBM(max) significantly progressed
      (0.010+/-0.004 mm per year; P=0.01) in group A (hydrochlorothiazide alone) but
      not in groups B, C, and D. CBM(max) changes in groups B, C, and D were
      significantly different from changes in group A. Changes in group A were
      concentrated at the bifurcations. "Clinic" and "ambulatory" blood pressure
      reductions were not significantly different between groups, but total and low
      density lipoprotein cholesterol decreased by approximately 1 mmol/L in groups C
      and D. CONCLUSIONS: Progression of carotid atherosclerosis occurred with
      hydrochlorothiazide but not with fosinopril. Progression could also be avoided by
      associating pravastatin with hydrochlorothiazide.

PMID- 15514193
TI  - Sex difference in the effect of time from symptoms to surgery on benefit from
      carotid endarterectomy for transient ischemic attack and nondisabling stroke.
AB  - BACKGROUND AND PURPOSE: Early studies showed that carotid endarterectomy (CEA)
      carried a high risk if performed within days after a large ischemic stroke.
      Therefore, many surgeons delay CEA for 4 to 6 weeks after any stroke. To
      determine the effect of delay to CEA on operative risk and benefit, we pooled
      data from the North American Symptomatic Carotid Endarterectomy Trial and the
      European Carotid Surgery Trial. METHODS: Risk of ipsilateral ischemic stroke in
      the medical group, operative risk of stroke and death, and overall benefit from
      surgery were determined in relation to the time from the last symptomatic event
      to randomization. Operative risk of stroke and death was also determined in
      relation to the time to surgery. Analyses were stratified by sex and type of
      presenting event. RESULTS: The 30-day perioperative risk of stroke and death was
      unrelated to the time since the last symptomatic event and was not increased in
      patients operated <2 weeks after nondisabling stroke. In contrast, the risk of
      ipsilateral ischemic stroke in the medical group fell rapidly with time since
      event (P<0.001), as did the absolute benefit from surgery (P=0.001). This decline
      in benefit with time was unrelated to the type of presenting event but was more
      pronounced in women than men (difference P<0.001). Benefit in women was confined
      to those randomized <2 weeks after their last event, irrespective of severity of
      stenosis. CONCLUSIONS: CEA can be performed safely within 2 weeks of nondisabling
      ischemic stroke. Benefit from endarterectomy declines rapidly with increasing
      delay, particularly in women.

PMID- 15514194
TI  - Anteromedian, central, and posterolateral infarcts of the thalamus: three variant
      types.
AB  - BACKGROUND AND PURPOSE: Thalamic infarcts have traditionally been classified into
      4 territories: anterior, paramedian, inferolateral, and posterior. The purpose of
      this study was to review this classical versus variant distribution in patients
      with thalamic stroke. METHODS: We reviewed all patients with a first clinical
      stroke included in the Lausanne Stroke Registry between 1990 and 2002. Among 71
      patients with an acute stroke isolated to the thalamus confirmed by MRI, we
      selected all patients with lesions outside the classical territories and studied
      their clinical, etiological, and radiological features. RESULTS: A total of 21
      patients (30% of all thalamic stroke patients) showed infarction outside the
      classical territories, allowing us to delineate 3 variant distributions: (1)
      Anteromedian territory (9 patients [13%]) involving anterior and paramedian
      territories, with predominantly cognitive impairment, including executive
      dysfunction, anterograde amnesia, and aphasia in left-sided or bilateral lesions.
      The most frequent stroke mechanism was cardiac embolism. (2) Central territory (4
      patients [6%]), with lesions on the central part of the thalamus, resulting in a
      variety of neurological and neuropsychological signs, reflecting the involvement
      of several adjacent structures. Microangiopathy was the most frequent etiology.
      (3) Posterolateral territory (8 patients [11%]), involving inferolateral and
      posterior territories, with hemihypesthesia as the most frequent manifestation,
      followed by hemiataxia, executive dysfunction, and aphasia in left-sided lesions.
      Artery-to-artery embolism and microangiopathy were the main stroke mechanisms.
      CONCLUSIONS: We describe 3 variant topographic patterns of thalamic infarction
      with distinct manifestations and etiologies. We postulate that these infarcts are
      the result of a variation in thalamic arterial supply or reflect borderzone
      ischemia.

PMID- 15514195
TI  - Elastin and calcium rather than collagen or lipid content are associated with
      echogenicity of human carotid plaques.
AB  - BACKGROUND AND PURPOSE: Echolucent carotid plaques have been associated with
      increased risk for stroke. Histological studies suggested that echolucent plaques
      are hemorrhage- and lipid-rich, whereas echogenic plaques are characterized by
      fibrosis and calcification. This is the first study to relate echogenicity to
      plaque composition analyzed biochemically. METHODS: Echogenicity of human carotid
      plaques was analyzed by standardized high-definition ultrasound and classified
      into echolucent, with gray-scale median (GSM) <32 and echogenic with GSM > or
      =32. The biochemical composition of the plaques was assessed by fast-performance
      liquid chromotography and high-performance thin-layer chromotography. RESULTS: As
      assessed biochemically (milligrams per gram [mg/g]), echolucent plaques contained
      less hydroxyapatite (43.8 [SD 41.2] mg/g versus 121.6 [SD 106.2] mg/g; P=0.018),
      more total elastin (1.7 [SD 0.4] mg/g versus 1.2 [SD 0.4] mg/g; P=0.008), and
      more intermediate-size elastin forms (1.2 [SD 0.3] mg/g versus 0.8 [SD 0.4] mg/g;
      P=0.018). There was no difference in collagen amount between echogenic and
      echolucent plaques, neither biochemically (15.3 [SD 3.7] mg/g versus 14.4 [SD
      3.4] mg/g) nor histologically (13.4 [SD 4.9] % versus 13.0 [SD 5.6] %).
      Cholesterol esters, unesterified cholesterol, and triglycerides were increased in
      plaques associated with symptoms (22.5 [SD 23.3] mg/g versus 13.3 [SD 3.2];
      P=0.04), but no differences were detected between echolucent and echogenic
      plaques (13.5 [SD 4.0] versus 20.2 [SD 21.5] mg/g). Similar results were obtained
      by Oil Red O staining (symptomatic 7.6 [SD 4.7] % versus asymptomatic 4.2 [SD
      3.6] %; P=0.03; echolucent 5.9 [SD 4.1] % versus echogenic 5.0 [SD 4.0] % of
      area). CONCLUSIONS: Echogenicity of carotid plaques is mainly determined by their
      elastin and calcium but not collagen or lipid content. In addition, echolucency
      is associated to higher elastin content.

PMID- 15514196
TI  - Internal carotid artery stenosis measurement: comparison of 3D computed
      rotational angiography and conventional digital subtraction angiography.
AB  - BACKGROUND AND PURPOSE: Clinical trials have shown that carotid endarterectomy
      reduces stroke risk in symptomatic individuals with severe internal carotid
      artery (ICA) stenosis. As a result of these trials, digital subtraction
      angiography (DSA) became a standard of reference for ICA stenosis diagnosis.
      Newer 3D techniques provide a larger number of views than DSA, which may
      influence the estimated degree of stenosis. We evaluate this possibility by
      directly comparing stenosis grades from 3D computed rotational angiography (CRA)
      and DSA. METHODS: As a prospective diagnostic study, we performed CRA and DSA on
      26 consecutive symptomatic patients. Only 1 angiographic procedure was performed
      on normal asymptomatic arteries, yielding 42 arteries for comparison. Four
      neuroradiologists graded the CRA maximum intensity projections (MIPs) and DSA
      images, according to the North American Symptomatic Carotid Endarterectomy Trial
      guidelines. CRA studies included a search for the narrowest view by evaluating 60
      MIPs generated at 3 degrees intervals and measurement of actual artery diameters.
      Artery diameters and stenosis grades were analyzed graphically; statistical
      significance was determined using a paired t test. RESULTS: The mean difference
      of 1.2% (CI, -18%, 21%) between CRA and DSA stenosis grades was not statistically
      significant (P=0.55). Agreement of the optimal CRA viewing angle was limited,
      with an interobserver variability of 24+/-13 degrees . The interobserver
      variability of DSA and CRA stenosis grades, 9.1% (CI, 0%, 21%) and 9.4% (CI, 0%,
      22%), respectively, was not significantly different (P=0.79). CONCLUSIONS: CRA
      provides stenosis grades equivalent to DSA, as well as absolute measurements,
      providing a comparison for newer 3D techniques.

PMID- 15514198
TI  - Predicting rtPA associated ICH in acute stroke.

PMID- 15514199
TI  - Editorial comment--Prime time for proactive blood glucose control?

PMID- 15514200
TI  - Magnitude and role of wall shear stress on cerebral aneurysm: computational fluid
      dynamic study of 20 middle cerebral artery aneurysms.
AB  - BACKGROUND AND PURPOSE: Wall shear stress (WSS) is one of the main pathogenic
      factors in the development of saccular cerebral aneurysms. The magnitude and
      distribution of the WSS in and around human middle cerebral artery (MCA)
      aneurysms were analyzed using the method of computed fluid dynamics (CFD).
      METHODS: Twenty mathematical models of MCA vessels with aneurysms were created by
      3-dimensional computed tomographic angiography. CFD calculations were performed
      by using our original finite-element solver with the assumption of Newtonian
      fluid property for blood and the rigid wall property for the vessel and the
      aneurysm. RESULTS: The maximum WSS in the calculated region tended to occur near
      the neck of the aneurysm, not in its tip or bleb. The magnitude of the maximum
      WSS was 14.39+/-6.21 N/m2, which was 4-times higher than the average WSS in the
      vessel region (3.64+/-1.25 N/m2). The average WSS of the aneurysm region (1.64+/
      1.16 N/m2) was significantly lower than that of the vessel region (P<0.05). The
      WSSs at the tip of ruptured aneurysms were markedly low. CONCLUSIONS: These
      results suggest that in contrast to the pathogenic effect of a high WSS in the
      initiating phase, a low WSS may facilitate the growing phase and may trigger the
      rupture of a cerebral aneurysm by causing degenerative changes in the aneurysm
      wall. The WSS of the aneurysm region may be of some help for the prediction of
      rupture.

PMID- 15514201
TI  - Quantitative trait locus mapping of genetic modifiers of metabolic syndrome and
      atherosclerosis in low-density lipoprotein receptor-deficient mice:
      identification of a locus for metabolic syndrome and increased atherosclerosis on
      chromosome 4.
AB  - OBJECTIVE: The purpose of this study was to examine genetic factors responsible
      for metabolic syndrome and atherosclerosis in a setting of low-density
      lipoprotein (LDL) receptor deficiency in a cross between C57BL/6J (B6) and
      PERA/Ei (PERA) inbred mouse strains. METHODS AND RESULTS: Comparison of metabolic
      phenotypes in B6 and PERA strains revealed the PERA genetic background to be
      dramatically more susceptible to hyperleptinemia, hyperglycemia,
      hypertriglyceridemia, elevated insulin levels, and body fat increase than the B6
      background. To facilitate genetic analysis, metabolic syndrome-related traits and
      atherosclerotic lesion area were measured in 167 [(PERAxB6.129S7
      Ldlr(tm1Her))xB6.129S7-Ldlr(tm1Her)]N2 male and female backcross mice that were
      homozygous for the Ldlr null allele. Quantitative trait locus analysis was
      performed using 153 polymorphic microsatellite markers spanning the genome. On
      chromosome 4, we identified a locus influencing plasma triglyceride, insulin, and
      leptin concentrations, body weight, and atherosclerosis. Several other genetic
      loci were identified with separate effects on plasma insulin, body weight, high
      density lipoprotein cholesterol, and atherosclerosis. CONCLUSIONS: The PERA
      strain is highly susceptible to the development of metabolic syndrome after
      feeding a Western-type diet. This susceptibility is due, in part, to a locus on
      murine chromosome 4 in which PERA alleles predispose to adiposity, increased
      insulin, and accelerated atherogenesis in the absence of marked hyperlipidemia.

PMID- 15514202
TI  - Low-density lipoprotein from apolipoprotein E-deficient mice induces macrophage
      lipid accumulation in a CD36 and scavenger receptor class A-dependent manner.
AB  - OBJECTIVE: To investigate the potential of circulating low-density lipoprotein
      (LDL), isolated from apolipoprotein E (apoE)-deficient mice (E-/-LDL) and from
      LDL receptor-deficient mice (Lr-/-LDL), to induce foam cell formation. METHODS
      AND RESULTS: Binding studies using COS-7 cells overexpressing CD36, J774 cells,
      and mouse peritoneal macrophages (MPMs) unexpectedly showed for the first time
      that E-/-LDL, which is enriched in cholesterol, is a high-affinity ligand for
      CD36 and exhibited greater macrophage uptake than Lr-/-LDL or normal LDL. Minimal
      copper-mediated oxidization of Lr-/-LDL or C57LDL in vitro resulted in increased
      ligand internalization, although cell uptake of these oxidized LDLs was lower
      than that of E-/-LDL, even at oxidation levels similar to that found in E-/-LDL.
      Treatment of MPMs with E-/-LDL and Lr-/-LDL (to a 2- to 3-fold lesser extent),
      but not normal LDL, resulted in significant cellular cholesteryl ester
      accumulation and foam cell formation. Experiments using MPMs lacking CD36,
      scavenger receptor class A (SR-A), or both, indicated a major contribution of
      CD36 ( approximately 50%), and to a lesser extent, SR-A (24% to 30%), to E-/-LDL
      uptake. CONCLUSIONS: Because of its increased state of oxidation and high
      cholesterol content, LDL in apoE-deficient mice acts in a proatherogenic manner,
      without requiring further modification in the vascular wall, to induce foam cell
      formation through its uptake by scavenger receptors.

PMID- 15514203
TI  - ATVB in focus: redox mechanisms in blood vessels.
AB  - Reactive oxygen species have been implicated in the pathogenesis of virtually
      every stage of vascular lesion formation, hypertension, and other vascular
      diseases. We are currently gaining insight into important sources of reactive
      oxygen species in the vessel wall, including the NADPH oxidases, xanthine
      oxidase, uncoupled nitric oxide synthase, and mitochondrial sources. Although
      various reactive oxygen species have pathological roles, some serve as important
      signaling molecules that modulate vascular tone, growth, and remodeling. In the
      next several months, a series of articles in Arteriosclerosis, Thrombosis, and
      Vascular Biology attempt to further elucidate how reactive oxygen species are
      produced by vascular cells and the roles of these in vascular homeostasis. This
      series promises to provide a valuable update on a wide variety of issues related
      to the biochemistry, molecular biology, and physiology of these important and
      fascinating molecules. Reactive oxygen species have been implicated in the
      pathogenesis of virtually every stage of vascular lesion formation, hypertension,
      and other vascular diseases. Upcoming series of articles in Arteriosclerosis,
      Thrombosis, and Vascular Biology help elucidate how reactive oxygen species are
      produced by vascular cells and their role in vascular homeostasis.

PMID- 15514204
TI  - Immunomodulation of atherosclerosis: implications for vaccine development.
AB  - A number of studies have shown activation of the immune system throughout various
      stages of atherosclerosis. Recent observations have suggested that activation of
      immune responses may promote atherosclerosis on one hand by inducing and
      perpetuating arterial inflammation, whereas on the other hand, selective
      activation of certain immune functions may inhibit atherosclerosis and arterial
      inflammation. These observations suggest the possibility that selective
      suppression of proatherogenic immune responses or selective activation of
      antiatherogenic immune responses may provide new approaches for atherosclerosis
      prevention and treatment. Several antigens activating immune responses affecting
      development of atherosclerosis have been identified. These immune responses may
      be modulated by presenting the antigens together with different types of
      adjuvants as well as through the route of administration. In this review, we
      summarize recent experimental studies using immunomodulatory approaches for
      treatment of atherosclerosis.

PMID- 15514205
TI  - Vascular injury induces expression of periostin: implications for vascular cell
      differentiation and migration.
AB  - OBJECTIVE: Periostin mRNA is among the most strongly upregulated transcripts in
      rat carotid arteries after balloon injury. The goal of the present study was to
      gain insight into the significance of periostin in the vasculature. METHODS AND
      RESULTS: Periostin expression after injury was localized to smooth muscle cells
      of the neointima and the adventitia. The expression of periostin in smooth muscle
      cells in vitro was not regulated by cytokines such as fibroblast growth factor-2
      (FGF-2). In contrast, stimulation of MC3T3-E1 osteoblastic cells, NIH3T3
      fibroblasts, or mesenchymal C3H10T1/2 cells with FGF-2 reduced periostin mRNA
      levels to <5% of controls, whereas conversely bone morphogenetic protein-2 (BMP
      2) increased periostin mRNA levels. Periostin expression was induced and
      maintained during retinoic acid-induced smooth muscle cell differentiation in
      A404 cells. In addition, overexpression of periostin in C3H10T1/2 cells caused an
      increase in cell migration that could be blocked with an anti-periostin antibody.
      CONCLUSIONS: Periostin expression is associated with smooth muscle cell
      differentiation in vitro and promotes cell migration. Unlike other mesenchymally
      derived cell lines, periostin expression is not regulated by FGF-2 in smooth
      muscle cells. This distinction may be useful in discriminating smooth muscle and
      fibroblast lineages.

PMID- 15514206
TI  - No association between plasma levels of plant sterols and atherosclerosis in mice
      and men.
AB  - OBJECTIVE: Sitosterolemia is characterized by elevated plasma levels of plant
      sterols, hypercholesterolemia and premature coronary heart disease (CHD). CHD
      develops in some subjects with sitosterolemia, despite having normal plasma
      cholesterol levels, suggesting that high circulating levels of plant sterols may
      be atherogenic. We tested whether elevated plasma levels of plant sterols
      (sitosterol and campesterol) were associated with atherosclerosis in genetically
      modified mice and in middle-aged men and women. METHODS AND RESULTS: Wild-type
      and hypercholesterolemic female mice with >20-fold higher plasma levels of plant
      sterols because of inactivation of the ATP-binding cassette (ABC) half
      transporters G5 and G8 (G5G8-/-mice) were fed chow or Western diets for 7 months.
      No significant differences in aortic lesion area were found when the
      sitosterolemic mice were compared with littermate controls. To determine whether
      plasma levels of plant sterols were associated with coronary atherosclerosis in
      humans, the relationship between plasma plant sterols and coronary calcium
      (detected by electron beam computer tomography) was examined in 2542 subjects
      aged 30 to 67 years. Plasma levels of cholesterol, but not sitosterol or
      campesterol, were significantly higher in subjects with coronary calcium.
      CONCLUSIONS: The results of this study do not support an association between
      elevated plasma levels of plant sterols and atherosclerosis.

PMID- 15514207
TI  - Effect of low dose atorvastatin versus diet-induced cholesterol lowering on
      atherosclerotic lesion progression and inflammation in apolipoprotein E*3-Leiden
      transgenic mice.
AB  - OBJECTIVE: To evaluate whether low-dose atorvastatin suppresses atherosclerotic
      lesion progression and inflammation in apolipoprotein E*3 (apoE*3)-Leiden mice
      beyond its cholesterol-lowering effect. METHODS AND RESULTS: ApoE*3-Leiden mice
      were fed a high-cholesterol (HC) diet until mild atherosclerotic lesions had
      formed. Subsequently, HC diet feeding was continued or mice received HC
      supplemented with 0.002% (w/w) atorvastatin (HC+A), resulting in 19% plasma
      cholesterol lowering, or mice received a low-cholesterol (LC) diet to establish a
      plasma cholesterol level similar to that achieved in the HC+A group. HC+A and LC
      diet reduced, significantly and to the same extent, lesion progression and
      complication in the aortic root, as assessed by measuring total atherosclerotic
      lesion area, lesion severity, and macrophage and smooth muscle cell area. In the
      aortic arch, HC+A but not LC blocked lesion progression. HC+A and LC reduced
      vascular inflammation (ie, expression of macrophage migration inhibitory factor ,
      plasminogen activator inhibitor- 1, matrix metalloproteinase-9), but HC+A
      additionally suppressed vascular cell adhesion molecule-1 expression and, in
      parallel, monocyte adhesion. In contrast, low-dose atorvastatin showed no
      antiinflammatory action toward hepatic inflammation markers (serum amyloid A, C
      reactive protein [CRP]) in apoE*3-Leiden mice and human CRP transgenic mice.
      CONCLUSIONS: Low-dose atorvastatin cholesterol-dependently reduces lesion
      progression in the aortic root but shows antiinflammatory vascular activity and
      tends to retard atherogenesis in the aortic arch beyond its cholesterol-lowering
      effect.

PMID- 15514208
TI  - Antiangiogenic activity of semisynthetic biotechnological heparins: low-molecular
      weight-sulfated Escherichia coli K5 polysaccharide derivatives as fibroblast
      growth factor antagonists.
AB  - OBJECTIVE: Low-molecular-weight heparin (LMWH) exerts antitumor activity in
      clinical trials. The K5 polysaccharide from Escherichia coli has the same
      structure as the heparin precursor. Chemical and enzymatic modifications of K5
      polysaccharide lead to the production of biotechnological heparin-like compounds.
      We investigated the fibroblast growth factor-2 (FGF2) antagonist and
      antiangiogenic activity of a series of LMW N,O-sulfated K5 derivatives. METHODS
      AND RESULTS: Surface plasmon resonance analysis showed that LMW-K5 derivatives
      bind FGF2, thus inhibiting its interaction with heparin immobilized to a BIAcore
      sensor chip. Interaction of FGF2 with tyrosine-kinase receptors (FGFRs), heparan
      sulfate proteoglycans (HSPGs), and alpha(v)beta3 integrin is required for
      biological response in endothelial cells. Similar to LMWH, LMW-K5 derivatives
      abrogate the formation of HSPG/FGF2/FGFR ternary complexes by preventing FGF2
      mediated attachment of FGFR1-overexpressing cells to HSPG-bearing cells and
      inhibit FGF2-mediated endothelial cell proliferation. However, LMW-K5
      derivatives, but not LMWH, also inhibit FGF2/alpha(v)beta3 integrin interaction
      and consequent FGF2-mediated endothelial cell sprouting in vitro and angiogenesis
      in vivo in the chick embryo chorioallantoic membrane. CONCLUSIONS: LMW N,O
      sulfated K5 derivatives affect both HSPG/FGF2/FGFR and FGF2/alpha(v)beta3
      interactions and are endowed with FGF2 antagonist and antiangiogenic activity.
      These compounds may provide the basis for the design of novel LMW heparin-like
      angiostatic compounds.

PMID- 15514209
TI  - Dimorphism in the P2Y1 ADP receptor gene is associated with increased platelet
      activation response to ADP.
AB  - OBJECTIVE: The platelet ADP receptors P2Y1 and P2Y12 play a pivotal role in
      platelet aggregation. There is marked interindividual variation in platelet
      response to ADP. We studied whether genetic variants in the P2Y1 or P2Y12 genes
      affect platelet response to ADP. METHODS AND RESULTS: The P2Y1 and P2Y12 genes
      were screened for polymorphisms. Associations between selected polymorphisms and
      the platelet response to ADP (0.1, 1.0, and 10 micromol/L), assessed by whole
      blood flow cytometric measurement of fibrinogen binding to activated glycoprotein
      IIb-IIIa, were then determined in 200 subjects. Five polymorphisms were found in
      the P2Y1 gene and 11 in the P2Y12 gene. All polymorphisms were silent. A P2Y1
      gene dimorphism, 1622AG, was associated with a significant (P=0.007) effect on
      platelet ADP response, with a greater response in carriers of the G allele
      (frequency 0.15). The effect was seen at all concentrations of ADP but greatest
      at 0.1 mumol/L ADP, where the response in GG homozygotes was on average 130%
      higher than that seen in AA homozygotes (P=0.006). CONCLUSIONS: A common genetic
      variant at the P2Y1 locus is associated with platelet reactivity to ADP. This
      genotype effect partly explains the interindividual variation in platelet
      response to ADP and may have clinical implications with regard to thrombotic
      risk.

PMID- 15514210
TI  - Statins inhibit synthesis of an oxysterol ligand for the liver x receptor in
      human macrophages with consequences for cholesterol flux.
AB  - OBJECTIVE: Cholesterol efflux from macrophages in the artery wall, a key
      cardioprotective mechanism, is largely coordinated by the nuclear oxysterol
      activated liver X receptor, LXRalpha. We investigated the effect of statins on
      LXR target gene expression and cholesterol efflux from human macrophages. METHODS
      AND RESULTS: In human macrophages (THP-1 cell line and primary cells), the
      archetypal statin, compactin, greatly reduced mRNA levels of 2 LXR target genes,
      ABCA1 and ABCG1 mRNA, as well as decreased cholesterol efflux. Commonly
      prescribed statins also downregulated LXR target gene expression in THP-1 cells.
      We provide several lines of evidence indicating that statins decrease expression
      of LXR target genes by inhibiting the synthesis of an oxysterol ligand for LXR,
      24(S),25-epoxycholesterol. When THP-1 cells were cholesterol-loaded via
      incubation with acetylated low-density lipoprotein, synthesis of 24(S),25
      epoxycholesterol was greatly reduced and the downregulatory effect of compactin
      on ABCA1 mRNA levels and cholesterol efflux was lost. CONCLUSIONS: Our results
      suggest that statins may downregulate cholesterol efflux from nonloaded human
      macrophages by inhibiting synthesis of an oxysterol ligand for LXR. Further work
      is needed to determine how relevant our observations are to arterial foam cells
      in vivo.

PMID- 15514211
TI  - Probucol inhibits ABCA1-mediated cellular lipid efflux.
AB  - OBJECTIVE: ATP-binding cassette transporter A1 (ABCA1) mediates the efflux of
      lipids from cells to lipid-poor apolipoproteins. In this article, we characterize
      the effect of probucol on cellular ABCA1-mediated lipid efflux. METHODS AND
      RESULTS: Probucol inhibited cholesterol efflux up to 80% in J774 macrophages
      expressing ABCA1. In Fu5AH hepatoma cells that contain scavenger receptor class
      B, type I, but not functional ABCA1, we observed no effect of probucol on
      cholesterol efflux. Probucol inhibited cholesterol efflux from normal human skin
      fibroblasts but not from fibroblasts from a Tangier patient. Fluorescent confocal
      microscopy and biotinylation assay demonstrated that in J774 cells probucol
      impaired the translocation of ABCA1 from intracellular compartments to the plasma
      membrane. Probucol also inhibited the formation of an ABCA1-linked cholesterol
      oxidase sensitive plasma membrane domain. Consistent with the inhibitory effect
      on ABCA1 translocation to the plasma membrane, probucol reduced cell surface
      specific [125I]-labeled apolipoprotein-AI binding. CONCLUSIONS: We conclude that
      probucol is an effective inhibitor of ABCA1-mediated cholesterol efflux without
      influencing scavenger receptor class B type I-mediated efflux. The inhibition of
      ABCA1 translocation to the plasma membrane may in part explain the reported in
      vivo high-density lipoprotein-lowering action of probucol.

PMID- 15514212
TI  - Granulocyte macrophage-colony stimulating factor increases the expression of
      histamine and histamine receptors in monocytes/macrophages in relation to
      arteriosclerosis.
AB  - OBJECTIVE: To study the effect of granulocyte macrophage-colony-stimulating
      factor (GM-CSF) on histamine metabolism in arteriosclerosis, the expression of
      histidine decarboxylase (HDC; histamine-producing enzyme), histamine receptors 1
      and 2 (HH1R and HH2R), and GM-CSF was investigated in human and mouse
      arteriosclerotic carotid arteries. Furthermore, the molecular mechanisms of GM
      CSF-induced HDC and HH1R expression in monocytic U937 cells were investigated.
      METHODS AND RESULTS: Immunohistochemistry showed that atherosclerotic human
      coronary and mouse ligated carotid arteries contained HDC-expressing macrophages.
      Gene expression of HDC, HH1R, HH2R, and GM-CSF was also detected in the lesions.
      In U937 cells, GM-CSF enhanced histamine secretion and gene expression of HDC and
      HH1R. A promoter assay showed that GM-CSF enhanced gene transcription of HDC and
      HH1R but not HH2R. CONCLUSIONS: The present results indicate that HDC and HHR are
      expressed in arteriosclerotic lesion, and that GM-CSF induces HDC and HH1R
      expression in monocytes. Locally produced histamine might participate in
      atherogenesis by affecting the expression of atherosclerosis-related genes in
      monocytes and smooth muscle cells. The presence of histamine-producing
      macrophages and gene expression of histamine receptors and GM-CSF was
      demonstrated in arteriosclerotic lesions. In monocytic U937 cells, GM-CSF
      upregulated the expression of histamine and HH1R. Coordinated expression of
      histamine and its receptors by GM-CSF would participate in atherogenesis by
      affecting monocytic and SMC gene expression.

PMID- 15514213
TI  - 2-chlorohexadecanal derived from hypochlorite-modified high-density lipoprotein
      associated plasmalogen is a natural inhibitor of endothelial nitric oxide
      biosynthesis.
AB  - OBJECTIVE: Myeloperoxidase, a heme enzyme that is present and active in human
      atherosclerotic lesions, provides a source for the generation of proinflammatory
      chlorinated reactants contributing to endothelial dysfunction. Modification of
      high-density lipoprotein (HDL) by hypochlorous acid/hypochlorite (HOCl/OCl-)
      [correction]-generated in vivo by the myeloperoxidase-hydrogen peroxide-chloride
      system of activated phagocytes-forms a proatherogenic lipoprotein particle that
      binds to and is internalized by endothelial cells. METHODS AND RESULTS: Here we
      show that HDL, modified with physiologically relevant HOCl concentrations,
      attenuates the expression and activity of vasculoprotective endothelial nitric
      oxide synthase. HOCl-HDL promotes dislocalization of endothelial nitric oxide
      synthase from the plasma membrane and perinuclear location of human umbilical
      venous endothelial cells. We could identify 2-chlorohexadecanal as the active
      component mediating this inhibitory activity. This chlorinated fatty aldehyde is
      formed during HOCl-mediated oxidative cleavage of HDL-associated plasmalogen.
      CONCLUSIONS: 2-Chlorohexadecanal, produced by the myeloperoxidase-hydrogen
      peroxide-chloride system of activated phagocytes may act as a mediator of
      vascular injury associated with ischemia-reperfusion injury, glomerulosclerosis,
      and atherosclerosis.

PMID- 15514214
TI  - Public health practice vs public health research: the role of the institutional
      review board.

PMID- 15514215
TI  - What can oral public health learn from Finland?

PMID- 15514217
TI  - HIV topical microbicides: the current development strategy is fully justified.

PMID- 15514216
TI  - Breastfeeding and asthma in adolescents.

PMID- 15514218
TI  - Environment and health: capacity building for the future.

PMID- 15514219
TI  - A role for public health history.

PMID- 15514220
TI  - Plumbism reinvented: childhood lead poisoning in France, 1985-1990.
AB  - Although the history of childhood lead poisoning started a century ago in the
      United States, the first French cases were identified in 1985. Instead of merely
      adopting knowledge accumulated for decades, the public health professionals and
      activists involved had to reestablish, against incredulity from medical
      authorities and resistance from policymakers, all the evidence: that children
      were the main group concerned; that cases were not isolated but part of an
      epidemic; that wall paint in old, dilapidated apartments was the source of
      contamination; and that poor housing conditions, and not cultural practices, were
      responsible for the high incidence in African families. This "reinvention"
      illustrates more general sociological phenomena: discontinuities in medical
      history, strength of culturalist prejudices toward immigrants, resistance to
      socioeconomic interpretations of disease, and struggles between different
      perspectives in public health. The history shows that public health is the
      product of intellectual and political struggles to impose visions of the world.

PMID- 15514221
TI  - The origins of primary health care and selective primary health care.
AB  - I present a historical study of the role played by the World Health Organization
      and UNICEF in the emergence and diffusion of the concept of primary health care
      during the late 1970s and early 1980s. I have analyzed these organizations'
      political context, their leaders, the methodologies and technologies associated
      with the primary health care perspective, and the debates on the meaning of
      primary health care. These debates led to the development of an alternative, more
      restricted approach, known as selective primary health care. My study examined
      library and archival sources; I cite examples from Latin America.

PMID- 15514222
TI  - Uncertain advances: a review of the final phases of the smallpox eradication
      program in India, 1960-1980.
AB  - In this article, I describe the complex nature of the final phases of the Indian
      smallpox eradication program. I examine the unfolding of policies at different
      levels of administration and the roles played by a wide range of national and
      international actors. A careful examination of unpublished official
      correspondence, on which this article is largely based, shows that the program's
      managers were divided and that this division determined the timing of the
      achievement of eradication. This material also reveals that Indian health workers
      and bureaucrats were far more capable of reshaping policies in specific
      localities, often in response to local infrastructural and political concerns,
      than has been acknowledged in the historiography.

PMID- 15514223
TI  - The Christian Medical Commission and the development of the World Health
      Organization's primary health care approach.
AB  - The primary health care approach was introduced to the World Health Organization
      (WHO) Executive Board in January 1975. In this article, I describe the changes
      that occurred within WHO leading up to the executive board meeting that made it
      possible for such a radical approach to health services to emerge when it did. I
      also describe the lesser-known developments that were taking place in the
      Christian Medical Commission at the same time, developments that greatly enhanced
      the case for primary health care within WHO and its subsequent support by
      nongovernmental organizations concerned with community health.

PMID- 15514224
TI  - The making and breaking of Yugoslavia and its impact on health.
AB  - The creation of nation-states in Europe has generally been assumed to be
      intrinsic to modernization and to be irreversible. The disintegration of
      Czechoslovakia, the Soviet Union, and Yugoslavia demonstrates that the process is
      not irreversible. I argue that in the case of Yugoslavia, (1) disintegration was
      caused by the interaction between domestic policies with regard to nationalities
      and integration into the global economy and (2) the impact of the disintegration
      of the federation on health care and public health systems has been profound.
      Improving and converging measures of mortality before the collapse gave way to
      increasing disparities afterward. The lesson is that processes of individual and
      social modernization do not result in improvements in health and well-being that
      are necessarily irreversible or shared equally.

PMID- 15514225
TI  - Kenneth Olden, master fencer.

PMID- 15514226
TI  - Human testing of pesticides: ethical and scientific considerations.
AB  - I reviewed ethical and scientific aspects of 6 human pesticide-dosing studies
      submitted to the Environmental Protection Agency (EPA) for consideration during
      the pesticide reregistration process. All had serious ethical or scientific
      deficiencies-or both-including unacceptable informed consent procedures,
      unmanaged financial conflicts of interest, inadequate statistical power,
      inappropriate test methods and endpoints, and distorted results. Given today's
      knowledge of the effects of pesticides, there is no assurance that any such study
      can be completely free of short-term risks, long-term risks, or both. Therefore,
      there is no basis for allowing pesticide studies to continue or for using them
      during the pesticide reregistration process. An EPA committee that is free from
      political and financial conflicts of interest should review this practice.

PMID- 15514228
TI  - The Global Alliance for Vaccines and Immunization: is it a new model for
      effective public-private cooperation in international public health?
AB  - The Global Alliance for Vaccines and Immunization (GAVI) has in many ways been
      remarkably successful in revitalizing the international coalition of institutions
      and organizations concerned with getting vaccines to the children of the poorest
      countries. Many have seen this high-profile venture in public-private cooperation
      as a model for other groups concerned with more effectively helping to solve
      health problems in the developing world. We examined major flaws in the GAVI and
      argue that in fact the alliance does not represent a new paradigm for
      international public health. However, the experience of the GAVI may suggest an
      alternative, and more effective, way to conceptualize future global initiatives.

PMID- 15514227
TI  - Occupational health research in developing countries: a partner for social
      justice.
AB  - Occupational health remains neglected in developing countries because of
      competing social, economic, and political challenges. Occupational health
      research in developing countries should recognize the social and political
      context of work relations, especially the fact that the majority of developing
      countries lack the political mechanisms to translate scientific findings into
      effective policies. Researchers in the developing world can achieve tangible
      progress in promoting occupational health only if they end their professional
      isolation and examine occupational health in the broader context of social
      justice and national development in alliance with researchers from other
      disciplines. An occupational health research paradigm in developing countries
      should focus less on the workplace and more on the worker in his or her social
      context.

PMID- 15514229
TI  - A global perspective on vaccine safety and public health: the Global Advisory
      Committee on Vaccine Safety.
AB  - Established in 1999, the Global Advisory Committee on Vaccine Safety advises the
      World Health Organization (WHO) on vaccine-related safety issues and enables WHO
      to respond promptly, efficiently, and with scientific rigor to issues of vaccine
      safety with potential global importance. The committee also assesses the
      implications of vaccine safety for practice worldwide and for WHO policies. We
      describe the principles on which the committee was established, its modus
      operandi, and the scope of the work undertaken, both present and future. We
      highlight its recent recommendations on major issues, including the purported
      link between the measles-mumps-rubella vaccine and autism and the safety of the
      mumps, influenza, yellow fever, BCG, and smallpox vaccines as well as that of
      thiomersal-containing vaccines.

PMID- 15514230
TI  - Research and development of new vaccines against infectious diseases.
AB  - Infectious diseases are responsible for approximately 25% of global mortality,
      especially in children aged younger than 5 years. Much of the burden of
      infectious diseases could be alleviated if appropriate mechanisms could be put in
      place to ensure access for all children to basic vaccines, regardless of
      geographical location or economic status. In addition, new safe and effective
      vaccines should be developed for a variety of infections against which no
      effective preventive intervention measure is either available or practical. The
      public, private, and philanthropic sectors need to join forces to ensure that
      these new or improved vaccines are fully developed and become accessible to the
      populations in need as quickly as possible.

PMID- 15514231
TI  - Prevalence of chronic diseases in adults exposed to arsenic-contaminated drinking
      water.
AB  - Inorganic arsenic is naturally occurring in groundwaters throughout the United
      States. This study investigated arsenic exposure and self-report of 9 chronic
      diseases. We received private well-water samples and questionnaires from 1185
      people who reported drinking their water for 20 or more years. Respondents with
      arsenic levels of 2 microg/L or greater were statistically more likely to report
      a history of depression, high blood pressure, circulatory problems, and bypass
      surgery than were respondents with arsenic concentrations less than 2 microg/L.

PMID- 15514232
TI  - Risk of hospitalization among firefighters: the National Health Interview Survey,
      1986-1994.
AB  - This study assessed the risk of hospitalization among firefighters. Data were
      derived from a nationally representative sample of 235 897 employed men from the
      National Health Interview Survey. Firefighters aged 30 to 39 years were at
      significantly increased risk for hospitalization relative to other employed men
      in the same age group (odds ratio = 1.93; 95% confidence interval=1.21, 3.09).
      Findings from this study and others support the call for longitudinal studies to
      monitor the health of this high-risk occupational group.

PMID- 15514233
TI  - Epidemiology of hospitalizations resulting from dog bites in California, 1991
      1998.
AB  - We used population-based hospital discharge data to describe hospitalizations
      resulting from dog bites in California from 1991 through 1998, when there were
      6676 such hospitalizations (average 835 per year; range 732 to 930), and the
      annual cumulative incidence for all ages was 2.6 per 100 000. Children had more
      than twice the risk of adults, and Asians had lower rates than Whites. Children
      aged 0 to 9 years were more likely to suffer wounds to the head and face.

PMID- 15514234
TI  - Environmental justice, cumulative environmental risk, and health among low- and
      middle-income children in upstate New York.
AB  - OBJECTIVES: We documented inequitable, cumulative environmental risk exposure and
      health between predominantly White low-income and middle-income children residing
      in rural areas in upstate New York. METHODS: Cross-sectional data for 216 third-
      through fifth-grade children included overnight urinary neuroendocrine levels,
      noise levels, residential crowding (people/room), and housing quality. RESULTS:
      After control for income, maternal education, family structure, age, and gender,
      cumulative environmental risk exposure (0-3) (risk >1 SD above the mean for each
      singular risk factor [0, 1]) was substantially greater for low-income children.
      Cumulative environmental risk was positively correlated with elevated overnight
      epinephrine, norepinephrine, and cortisol in the low-income sample but not in the
      middle-income sample. CONCLUSIONS: Cumulative environmental risk exposure among
      low-income families may contribute to bad health, beginning in early childhood.

PMID- 15514235
TI  - High-intensity targeted screening for elevated blood lead levels among children
      in 2 inner-city Chicago communities.
AB  - OBJECTIVES: We assessed the prevalence of elevated blood lead levels (> or = 10
      micrograms of lead per deciliter of blood), risk factors, and previous blood lead
      testing among children in 2 high-risk Chicago, Ill, communities. METHODS: Through
      high-intensity targeted screening, blood lead levels were tested and risks were
      assessed among a representative sample of children aged 1 to 5 years who were at
      risk for lead exposure. RESULTS: Of the 539 children who were tested, 27% had
      elevated blood lead levels, and 61% had never been tested previously. Elevated
      blood lead levels were associated with chipped exterior house paint. CONCLUSIONS:
      Most of the children who lived in these communities--where the prevalence for
      elevated blood lead levels among children was 12 times higher than the national
      prevalence--were not tested for lead poisoning. Our findings highlight the need
      for targeted community outreach that includes testing blood lead levels in
      accordance with the American Academy of Pediatrics' recommendations.

PMID- 15514236
TI  - Racial and ethnic differences in the seroprevalence of 6 infectious diseases in
      the United States: data from NHANES III, 1988-1994.
AB  - OBJECTIVES: We examined racial/ethnic differences in the seroprevalence of
      selected infectious agents in analyses stratified according to risk categories to
      identify patterns and to determine whether demographic, socioeconomic, and
      behavioral characteristics explain these differences. METHODS: We analyzed data
      from the third National Health and Nutrition Examination Survey, comparing
      differences among groups in regard to the prevalence of infection with hepatitis
      A, B, and C viruses, Toxoplasma gondii, Helicobacter pylori, and herpes simplex
      virus type 2. RESULTS: Racial/ethnic differences were greater among those in the
      low-risk category. In the case of most infectious agents, odds associated with
      race/ethnicity were almost 2 times greater in that category than in the high-risk
      category. CONCLUSIONS: Stratification and adjustment for socioeconomic factors
      reduced or eliminated racial/ethnic differences in the prevalence of infection in
      the high-risk but not the low-risk group, wherein race/ethnicity remained
      significant and might have been a surrogate for unmeasured risk factors.

PMID- 15514237
TI  - Effects of restaurant and bar smoking regulations on exposure to environmental
      tobacco smoke among Massachusetts adults.
AB  - OBJECTIVES: We examined the association of local restaurant and bar regulations
      with self-reported exposure to environmental tobacco smoke among adults. METHODS:
      Data were derived from a telephone survey involving a random sample of
      Massachusetts households. RESULTS: Compared with adults from towns with no
      restaurant smoking restrictions, those from towns with strong regulations had
      more than twice the odds of reporting nonexposure to environmental tobacco smoke
      (odds ratio [OR]=2.74; 95% confidence interval [CI]=1.97, 3.80), and those from
      towns with some restrictions had 1.62 times the odds of reporting nonexposure
      (OR=1.62; 95% CI=1.29, 2.02). Bar smoking bans had even greater effects on
      exposure. CONCLUSIONS: Strong local clean indoor air regulations were associated
      with lower levels of reported exposure to environmental tobacco smoke in
      restaurants and bars.

PMID- 15514238
TI  - Disparities in smoking cessation between African Americans and Whites: 1990-2000.
AB  - OBJECTIVES: We examined disparities in smoking cessation rates between African
      Americans and Whites from 1990 through 2000. METHODS: We performed an analysis of
      smoking cessation with data from the National Health Interview Surveys of 30660
      African Americans and 209828 Whites, 18 to 64 years old, with adjustment for
      covariates in multiple logistic regression models. RESULTS: Whites were
      significantly more likely than African Americans to be former smokers, and this
      disparity in the quit ratio persisted from 1990 through 2000. After adjustment
      for covariates, disparities were substantially reduced especially among women.
      Among former smokers, African Americans were significantly more likely than
      Whites to have quit successfully within the past 10 years. CONCLUSIONS:
      Statistical adjustment for covariates reduces African American-White disparities
      in quit ratios, and recent cessation patterns suggest possible future reductions
      in disparities.

PMID- 15514239
TI  - Cigarette smoking and exposure to environmental tobacco smoke in China: the
      international collaborative study of cardiovascular disease in Asia.
AB  - OBJECTIVES: We estimated the prevalence of cigarette smoking and the extent of
      environmental tobacco smoke exposure (ETS) in the general population in China.
      METHODS: A cross-sectional survey was conducted on a nationally representative
      sample of 15540 Chinese adults aged 35-74 years in 2000-2001. Information on
      cigarette smoking was obtained by trained interviewers using a standard
      questionnaire. RESULTS: The prevalence of current cigarette smoking was much
      higher among men (60.2%) than among women (6.9%). Among nonsmokers, 12.1% of men
      and 51.3% of women reported exposure to ETS at home, and 26.7% of men and 26.2%
      of women reported exposure to ETS in their workplaces. On the basis of our
      findings, 147358000 Chinese men and 15895000 Chinese women aged 35-74 years were
      current cigarette smokers, 8658000 men and 108402000 women were exposed to ETS at
      home, and 19072000 men and 55372000 women were exposed to ETS in their
      workplaces. CONCLUSIONS: The high prevalence of cigarette smoking and
      environmental tobacco smoke exposure in the Chinese population indicates an
      urgent need for smoking prevention and cessation efforts.

PMID- 15514240
TI  - Immigration and acculturation in relation to health and health-related risk
      factors among specific Asian subgroups in a health maintenance organization.
AB  - OBJECTIVES: We sought to determine how risk factors for disease vary among Asian
      subgroups. METHODS: Using data from a case-control study conducted at Northern
      California Kaiser Medical Centers (from 1996 to 2001), we compared prevalence of
      selected risk factors among Asian subgroups and evaluated the associations of
      these risk factors with sociodemographic factors. RESULTS: Chinese and Japanese
      patients had a lower body mass index (kg/m(2)) than did other Asians. In all
      subgroups, being born in the United States was associated with having a body mass
      index greater than 25 kg/m(2). Compared with other Asians, more Japanese and
      multiple-race Asians smoked, and more Filipino and multiple-race Asian smokers
      started smoking at 18 years or younger. Filipinos and multiple-race Asians also
      were more likely to report diabetes. CONCLUSIONS: These data support the
      importance of efforts to distinguish among Asian subgroups in public health
      practice and research.

PMID- 15514241
TI  - High-risk alcohol consumption and late-life alcohol use problems.
AB  - OBJECTIVES: We used several different guidelines for appropriate alcohol use to
      identify patterns of high-risk alcohol consumption among older women and men and
      examined associations between these patterns and late-life alcohol use problems.
      METHODS: A sample of 1291 older adults participated in a survey of alcohol
      consumption and alcohol use problems and was studied again 10 years later.
      RESULTS: Depending on the guideline, 23% to 50% of women and 29% to 45% of men
      engaged in potentially unsafe alcohol use patterns. The likelihood of risky
      alcohol use declined over the 10 years; however, the numbers of drinks consumed
      per week and per day were associated with alcohol use problems at both assessment
      intervals. CONCLUSION: Our findings imply that guidelines for alcohol consumption
      should be no more liberal for older men than for older women.

PMID- 15514242
TI  - State trends in uninsurance among individuals aged 18 to 64 years: United States,
      1992-2001.
AB  - OBJECTIVES: We analyzed state-specific uninsurance trends among US adults aged 18
      to 64 years. METHODS: We used logistic regression models to examine Behavioral
      Risk Factor Surveillance System data for uninsurance from 1992 to 2001 in 47
      states. RESULTS: Overall, uninsurance rates increased in 35 states and remained
      unchanged in 12 states. Increases were observed among people aged 30 to 49 years
      (in 34 states) and 50 to 64 years (in 24 states), and increases were also
      observed among individuals at middle and low income levels (in 39 states and 19
      states, respectively), individuals employed for wages (in 33 states), and the
      self-employed (in 18 states). CONCLUSIONS: Among adults aged 18-64, rates of
      uninsurance increased in most states from 1992 through 2001. Decreased
      availability of employer-sponsored health insurance, rising health care costs,
      and state fiscal crises are likely to worsen the growing uninsurance problem.

PMID- 15514243
TI  - Correlates of sex trading among drug-using men who have sex with men.
AB  - OBJECTIVES: We examined correlates of trading sex for money, drugs, and shelter,
      or food among drug-using men who have sex with men (MSM). METHODS: Audio computer
      assisted self-interviewing questionnaires were completed by 387 MSM. The
      association of predictors with sex trading was assessed with chi(2) tests and
      multiple logistic regression. RESULTS: Sex-trading prevalence was 62.5% (95%
      confidence interval=57.7%, 67.4%). Sex trading was associated with crack use,
      injection drug use, childhood maltreatment, non-gay self-identification, and
      homelessness (adjusted odds ratios=3.72, 2.28, 2.62, 2.21, and 1.88,
      respectively). CONCLUSIONS: Multiple risk factors are associated with sex trading
      among MSM. Interventions may need to address crack and injection drug use,
      homelessness, and childhood maltreatment and target non-gay-identified MSM who
      engage in sex trading.

PMID- 15514244
TI  - Effects of macroeconomic trends on social security spending due to sickness and
      disability.
AB  - OBJECTIVES: We analyzed the relationship between macroeconomic conditions,
      measured as unemployment rate and social security spending, from 4 social
      security schemes and total spending due to sickness and disability. METHODS: We
      obtained aggregated panel data from 13 Organization for Economic Cooperation and
      Development member countries for 1980-1996. We used regression analysis and fixed
      effect models to examine spending on sickness benefits, disability pensions,
      occupational-injury benefits, survivor's pensions, and total spending. RESULTS: A
      decline in unemployment increased sickness benefits spending and reduced
      disability pension spending. These effects reversed direction after 4 years of
      unemployment. Inclusion of mortality rate as an additional variable in the
      analysis did not affect the findings. CONCLUSIONS: Macroeconomic conditions
      influence some reimbursements from social security schemes but not total
      spending.

PMID- 15514245
TI  - Effects on alcohol use and anxiety of the September 11, 2001, attacks and chronic
      work stressors: a longitudinal cohort study.
AB  - OBJECTIVES: We hypothesized that chronic stressors associated with an everyday
      social role (work) would interact with a traumatic macrosocial stressor (the
      terrorist attacks of September 11, 2001) in predicting mental health status
      (during the fall of 2001). METHODS: We used mail surveys returned as part of wave
      3 of a workplace cohort study, both before and after September 11, 2001, to
      assess decision latitude, sexual harassment, generalized workplace abuse,
      psychological distress, and alcohol use. We also used regression analyses to
      assess the main effect of September 11 and interactions between September 11 and
      stressors, after control for baseline mental health. RESULTS: The main effect of
      September 11 on elevated alcohol use was significant for women but not for men.
      For women, work stressors significantly interacted with experiencing the events
      of September 11 to affect alcohol use and anxiety outcomes. CONCLUSIONS: Women
      experiencing chronic work stressors were most vulnerable to elevated
      psychological distress and alcohol use after September 11, 2001.

PMID- 15514246
TI  - Inhibition of TRPM2 function by PARP inhibitors protects cells from oxidative
      stress-induced death.
AB  - TRPM2 is a member of the transient receptor potential (TRP) protein superfamily
      of calcium-permeable, voltage-independent ion channels expressed in nonexcitable
      cells. Activation of TRPM2 by oxidative stress results in calcium influx and
      susceptibility to cell death, whereas inhibition of TRPM2 function enhances cell
      survival. In the present edition of this journal, Fonfria et al. demonstrate a
      role for poly(ADP ribose) polymerase (PARP) as a mediator between oxidative
      stress and TRPM2 activation. They present evidence that inhibition of either PARP
      or TRPM2 protects cells from plasma membrane damage and cell death. The
      therapeutic implications of this important observation are discussed.

PMID- 15514247
TI  - Do low-affinity states of beta-adrenoceptors have roles in physiology and
      medicine?
AB  - The pharmacology once ascribed to the 'beta4-adrenoceptor' is now believed to be
      that of a low-affinity state of the beta1-adrenoceptor. The beta2-adrenoceptor
      may also have a low-affinity state or site, while the beta3-adrenoceptor--the
      original low-affinity beta-adrenoceptor--can display more than one pharmacology.
      In this issue, Mallem et al. show that CGP-12177 relaxes thoracic aorta rings
      from normal rats by stimulating vascular smooth muscle low-affinity beta1
      adrenoceptors, apparently linked in part to Gi protein. By contrast, in rings
      from hypertensive rats, CGP-12177 acts mainly via endothelial beta3
      adrenoceptors. This work raises the possibility that low-affinity states of beta
      adrenoceptors have physiological roles, and suggests that they might be drug
      targets.

PMID- 15514248
TI  - The link between selenium and chemoprevention: a case for selenoproteins.
AB  - Selenium is effective in reducing cancer incidence in animal models, and
      epidemiologic data, as well as supplementation trials, have indicated that
      selenium is likely to be effective in humans. The mechanism by which selenium
      prevents cancer remains unknown. The mammalian genome encodes 25 selenoprotein
      genes, each containing one or more molecules of selenium in the form of the amino
      acid selenocysteine, translationally inserted into the growing peptide in
      response to the UGA codon. There is evidence that several of these proteins may
      be involved with the mechanism by which selenium provides its anticancer effects.
      Data are reviewed indicating that genetic variants of the cytosolic glutathione
      peroxidase are associated with increased cancer risk, and that loss of one of the
      copies of this same gene may be involved with malignant progression. Similarly,
      allelic differences in the gene for a second selenoprotein, Sep15, may be
      relevant to the protection provided by selenium, and allelic loss at this locus
      have been reported as well. These data, along with the differential expression
      patterns reported for other selenoproteins in tumor vs. normal tissues, support
      the role of selenoproteins in the chemoprotection by selenium.

PMID- 15514249
TI  - Protective effects of high dietary potassium: nutritional and metabolic aspects.
AB  - Potassium (K+) requirements have been largely overlooked because severe
      deficiencies are uncommon due to the ubiquity of this element in foods. However,
      a transition toward modern ("Westernized") diets has led to a substantial decline
      of K+ intake compared with traditional food habits, and a large fraction of the
      population might now have suboptimal K+ intake. A high K+ intake was demonstrated
      to have protective effects against several pathologic states affecting the
      cardiovascular system, kidneys, and bones. Additionally, fruits and vegetables
      contain K/organic anion salts (malate, citrate), which exert alkalinizing
      effects, through KHCO(3)(-) generation, which serves to neutralize fixed acidity
      in urine. Low-grade metabolic acidosis, when not properly controlled, may
      exacerbate various catabolic processes (bone Ca++ mobilization, proteolysis),
      especially in the elderly. Fruits and vegetables are therefore receiving great
      attention in a strategy to increase the nutritional value of meals while reducing
      energy density and intake. The need to ensure a 2.5- to 3.5-g daily K+ supply
      from fruits and vegetables represents a strong rationale for the "5-10 servings
      per day" recommendations.

PMID- 15514250
TI  - Esmond Emerson Snell (1914-2003).

PMID- 15514251
TI  - Soy and mammographic breast density: plausible hypothesis but limited evidence in
      humans.

PMID- 15514252
TI  - Triiodothyronine treatment attenuates the induction of hepatic glycine N
      methyltransferase by retinoic acid and elevates plasma homocysteine
      concentrations in rats.
AB  - Recent studies indicated that hormonal imbalances have a role in modulating the
      metabolism of methyl groups and homocysteine, interrelated pathways that when
      disrupted, are associated with a number of pathologies. Retinoic acid (RA) was
      shown to induce hepatic glycine N-methyltransferase (GNMT), a key regulatory
      protein in methyl group metabolism, and to reduce circulating homocysteine
      levels. Because thyroid status influences the hepatic folate-dependent one-carbon
      pool and retinoids can alter thyroid hormone levels, the aim of this study was to
      examine the interaction between retinoids and thyroid function. For hypothyroid
      studies, rats were administered 0.5 g/L propylthiouracil in the drinking water
      for 15 d, and RA [30 micromol/(kg . d)] for the final 5 d. For hyperthyroid
      studies, rats were treated with RA [30 micromol/(kg . d)] for 8 d and
      triiodothyronine [T(3); 50 microg/(100 g . d)] the last 4 d. T(3) treatment
      prevented the RA-mediated increase in GNMT activity. However, GNMT abundance
      remained elevated, indicating that GNMT regulation by T(3) in RA-treated rats may
      be, at least in part, at the post-translational level. In addition, T(3)
      treatment elevated plasma levels of homocysteine 177%, an elevation that was
      prevented by RA. T(3)-mediated hyperhomocysteinemia may be due to a 70% decrease
      in hepatic betaine-homocysteine S-methyltransferase, the enzyme that catalyzes
      folate-independent remethylation of homocysteine, whereas the RA-mediated
      stimulation of hepatic homocysteine remethylation by folate-dependent methionine
      synthase may contribute to lowering plasma homocysteine levels. These findings
      indicate that thyroid hormones, alone and in conjunction with RA, play an
      important role in the regulation of methyl group and homocysteine metabolism.

PMID- 15514253
TI  - Depressed prostanoid-induced contractility of the gut in spontaneously
      hypertensive rats (SHR) is not affected by the level of dietary fat.
AB  - Dietary saturated fat (SF) has adverse effects on cardiac and vascular smooth
      muscle (VSM) contractility. Furthermore, VSM of spontaneously hypertensive rats
      (SHR) is overreactive to various biological stimuli. The aim of this study was to
      investigate the effects of increasing dietary fat as lard on gut contractility in
      SHR. Control Wistar-Kyoto (WKY) rats and SHR (13 wk old) were fed for 12 wk a
      diet containing 3% sunflower oil [low fat (LF), 3% total fat] or diets
      supplemented with 7% lard [medium fat (MF), 10% total fat] or 27% lard [high fat
      (HF), 30% total fat]. For ileal and colonic tissues (WKY and SHR), there was a
      lower total phospholipid PUFA (n-6)/(n-3) ratio with increased dietary SF (P <
      0.003). For WKY, increasing SF led to lower levels of the major SCFA and lower
      total SCFA levels in cecal digesta (P < 0.01). This trend was evident in SHR but
      significant only for butyrate (P < 0.01). Contractility responses were unaltered
      in ileum. In colon, there was a change of sensitivity (50% effective
      concentration) to angiotensin II in WKY (P < 0.05) due to increased SF and a
      change of sensitivity to prostaglandin (PG)E(2) and carbachol in SHR (P < 0.05).
      When the 3 dietary groups were combined, there was lower sensitivity (P < 0.01)
      and lower maximal contraction (P < 0.05) in ileum and lower maximal contraction
      in colon of SHR in response to PGF(2alpha) (P < 0.05) and PGE(2) (P < 0.01)
      compared with WKY. Unlike (n-3) PUFA, dietary SF had little overall effect on gut
      contractility. However, this is the first report of a defect in PG responsiveness
      from gut tissue from hypertensive rats.

PMID- 15514254
TI  - Lipoic acid and ascorbic acid affect plasma free amino acids selectively in the
      teleost fish pacu (Piaractus mesopotamicus).
AB  - Most studies on the antioxidants, lipoic acid (LA) and ascorbic acid (AA),
      focused on species that, unlike teleost fish, are not scurvy-prone, and are able
      to synthesize AA. The antioxidant properties of LA may make it useful in
      aquaculture nutrition, but several effects must first be investigated, and we
      address here plasma free amino acids (FAA). In mammals, LA and AA in high doses
      were claimed to alter plasma FAA profile; to our knowledge, however, no data are
      available in fish. We therefore studied the effects of dietary LA and AA on
      plasma FAA in the South American teleost fish pacu, which is being used
      increasingly in aquaculture. LA treatment decreased concentrations of 18 of 23
      individual FAA; specifically, dispensable and total FAA were significantly
      affected. Ornithine was elevated (+26%) in LA-treated fish and significantly
      decreased ratios of plasma [Arg]/[Orn] and other individual [FAA]/[Orn] were
      observed. LA and AA both affected sulfur FAA concentrations. Plasma cystine
      levels were significantly increased in the LA-supplemented groups. AA had little
      effect on most amino acids, and no interaction with LA was detected. AA
      supplementation did, however, significantly lower taurine (-42%) and
      cystathionine (-31%) levels in plasma. No effect on the branched chain:aromatic
      amino acid ratios was observed. The data indicate that at the dietary level
      studied, LA and AA independently affect selected plasma FAA in pacu, and suggest
      that any use of LA in particular as a dietary supplement should take into account
      an altered plasma FAA profile.

PMID- 15514255
TI  - Synthesis and secretion of apoC-I and apoE during maturation of human SW872
      liposarcoma cells.
AB  - Little is known about the regulation of apolipoprotein (apo) C-I production by
      human adipocytes. The aim of the present study, therefore, was to investigate the
      effect of different tissue culture conditions on the synthesis and secretion of
      apoC-I and apoE in human SW872 liposarcoma cells. After 3-4 d in culture (0.5 x
      10(6) cells/well, DMEM/F-12 medium with 10% fetal calf serum), cells reached
      confluence and became growth arrested. The molar ratio of apoE:apoC-I in the cell
      was 8.9 +/- 0.6 and in the medium was 6.6 +/- 0.5. After 17 d in culture, SW872
      cells contained significantly more cholesterol (100%) and triglyceride (3-fold)
      and secreted more apoC-I [4 vs. 17 d: 0.11 +/- 0.01 vs. 0.23 +/- 0.01 pmol/(10(6)
      cells . 24 h), P < 0.001] and apoE [0.7 +/- 0.1 vs. 3.1 +/- 0.3 pmol/(10(6) cells
      . 24 h), P < 0.001]. Cellular apoC-I increased 7-fold and apoE increased 16-fold.
      Cell maturation was associated with significantly higher levels of apoE mRNA but
      not apoC-I mRNA. Increases in cell lipids, apoC-I, and apoE were not dependent on
      the presence of extracellular lipids because similar changes occurred in cells
      incubated with lipoprotein-deficient serum or in cells incubated without serum.
      Treatment (7 d) of cells during maturation with insulin (10 or 1000 nmol/L)
      significantly reduced the secretion of apoC-I and apoE. These results demonstrate
      that in maturing SW872 cells, cholesterol and triglyceride accumulation in the
      presence or absence of extracellular lipids, is associated with increased apoC-I
      and apoE production. Furthermore, apoC-I and apoE production are differentially
      regulated at the transcriptional level, and long-term treatment with insulin has
      an inhibitory rather than stimulatory effect on apoC-I and apoE production.

PMID- 15514256
TI  - Soy isoflavones affect sterol regulatory element binding proteins (SREBPs) and
      SREBP-regulated genes in HepG2 cells.
AB  - Soy intake reduces cholesterol levels. However, both the identity of the soy
      component or components that contribute to this reduction and the cellular
      mechanism producing this reduction are unknown. Soy consists of protein, lipids,
      fiber, and phytochemicals including isoflavones. We propose that the isoflavone
      component of soy mediates this effect, at least in part, by affecting cellular
      sterol homeostasis. We investigated the effects of an isoflavone-containing soy
      extract and the individual isoflavones on the maturation of the sterol regulatory
      element binding proteins (SREBP) and the expression of SRE-regulated genes
      controlling lipid metabolism. We found a corresponding increase in the mature
      form of SREBP-2 in both soy extract- and isoflavone-treated HepG2 cells, whereas
      there was no significant change in the levels of SREBP-1. 3-Hydroxy-3
      methylglutaryl coenzyme A (HMG CoA) reductase protein and HMG CoA synthase mRNA
      levels also increased. When HepG2 cells were transiently transfected with HMG CoA
      synthase and LDL receptor reporter plasmids there was an increase in expression
      in response to soy extract or isoflavone treatment from both of these promoters,
      but this induction was blunted in the presence of sterols (P < 0.05). The
      mechanism responsible for this effect may be via a statin-like inhibition of HMG
      CoA reductase enzyme activity or by enhanced SREBP processing via the SREBP
      cleavage activating protein. We hypothesize that maturation of SREBP and
      induction of SRE-regulated genes produce an increase in surface LDL receptor
      expression that increases the clearance of plasma cholesterol, thus decreasing
      plasma cholesterol levels.

PMID- 15514257
TI  - 1,25-dihydroxycholecalciferol inhibits apoptosis in C3H10T1/2 murine fibroblast
      cells through activation of nuclear factor kappaB.
AB  - 1,25-dihydroxycholecalciferol [1,25(OH)(2)D(3)] is important in the regulation of
      cell growth, differentiation, and apoptosis. Previous results from our laboratory
      demonstrate that 1,25(OH)(2)D(3) inhibits vitamin E succinate (VES) mediated
      apoptosis in untransformed C3H10T1/2 mouse fibroblast cells. The current work
      investigated cell survival signaling pathways that may be activated by
      1,25(OH)(2)D(3), leading to protection from apoptosis. Results showed that
      nuclear factor kappaB (NFkappaB) transcriptional activity was significantly
      increased 1.8-fold over vehicle controls by 1,25(OH)(2)D(3) after 4 h of
      treatment. Protein kinase B/AKT, a downstream effector of phosphoinositide 3
      kinase (PI3K), was activated 4-fold and 8-fold at 2 and 4 h, respectively, after
      treatment with 1,25(OH)(2)D(3). Pretreatment with two PI3K inhibitors, LY294002
      and wortmannin, abolished the activation of NFkappaB by 1,25(OH)(2)D(3),
      suggesting that this pathway is essential for NFkappaB transcriptional
      activation. Additionally, the use of a p-21 activated kinase (PAK1) inhibitory
      construct (PAK(R299)) demonstrated that PAK1 was also required for NFkappaB
      transcriptional activation by 1,25(OH)(2)D(3). Inhibition of NFkappaB activity
      with transfection of the NFkappaB inhibitory construct (IkappaB(Ala32)) abolished
      the protective effect of 1,25(OH)(2)D(3) on VES-mediated apoptosis. In summary,
      NFkappaB transcriptional activation was essential to 1,25(OH)(2)D(3) protection
      from VES-mediated apoptosis and 1,25(OH)(2)D(3) regulated NFkappaB activity
      through PI3K and PAK pathways.

PMID- 15514258
TI  - Alcohol-reduced plasma IGF-I levels and hepatic IGF-I expression can be partially
      restored by retinoic acid supplementation in rats.
AB  - Chronic and excessive ethanol intake in rats results in low levels of hepatic
      retinoic acid (RA) either by inhibiting the biosynthesis of RA or by enhancing
      its catabolism of RA. Chronic ethanol intake also decreases both hepatic
      expression of insulin-like growth factor-I (IGF-I) and plasma IGF-I concentration
      in rats. It is not known whether RA supplementation in alcohol-fed rats can
      restore plasma IGF-I concentrations and hepatic IGF-I expression. In the present
      study, we examined both plasma IGF-I level and hepatic IGF-I mRNA expression in
      alcohol-fed rats with or without RA (100 microg/kg body weight) supplementation
      for 6 mo. Hepatic IGF-I mRNA levels and plasma IGF-I concentration were decreased
      (84 and 29%, respectively) significantly in alcohol-fed rats compared with the
      control. In contrast, RA supplementation in ethanol-fed rats partially restored
      both hepatic IGF-I mRNA levels and plasma IGF-I concentration compared with rats
      fed ethanol alone. These data suggest that alcohol-impaired hepatic RA status
      contributes to the decreased plasma IGF-I level and hepatic IGF-I expression in
      alcoholics.

PMID- 15514259
TI  - Increased expression of specific intestinal amino acid and peptide transporter
      mRNA in rats fed by TPN is reversed by GLP-2.
AB  - Intestinal function depends on the presence of luminal nutrients and is altered
      during starvation and refeeding. Amino acids are essential for enterocytes, but
      the luminal supply is compromised with changes in dietary intake. To test the
      hypothesis that during periods of restricted luminal nutrient availability
      mucosal cells undergo adaptations aimed toward preserving amino acid supply, the
      expression of amino acid and peptide transporter mRNAs was quantified in rats
      with no oral intake, whose nutritional status was maintained with total
      parenteral nutrition (TPN). The role of the intestinotrophic hormone glucagon
      like peptide-2 (GLP-2) was investigated in the adaptive responses. Rats were
      administered TPN with or without exogenous GLP-2. Amino acid and peptide
      transporter mRNAs in small intestine mucosa were measured by semiquantitative RT
      PCR. Compared with orally fed rats, removal of luminal nutrition increased the
      expression of ASCT1, SAT2, and GLYT1 mRNAs in the duodenum and of ASCT2, EAAC1,
      NBAT, and PepT1 mRNAs in the ileum. CAT1, PAT1, and SN2 mRNA abundances were
      unaffected. GLP-2 reversed these effects. Three subgroups of transporters were
      identified by regional differences in response to TPN. This may reflect differing
      roles for substrates of transporters located apically and basally and along the
      proximal-distal axis of the intestine. The importance of maintaining amino acid
      supply for intestinal mucosal cells is illustrated.

PMID- 15514260
TI  - Hepatic genes altered in expression by food restriction are not influenced by the
      low plasma glucose level in young male GLUT4 transgenic mice.
AB  - Because food restriction (FR) has a profound effect on most tissues, it is
      plausible that the modulation of aging by FR occurs through cellular processes
      such as gene expression. The effect of FR in lowering plasma glucose levels has
      been demonstrated in mice, rats, and nonhuman primates. The consistency of this
      finding suggests that decreased plasma glucose may be an important consequence of
      FR. Indeed, lowering plasma glucose in the absence of FR would be expected to
      change the expression of some of the same genes as seen with FR. GLUT4 transgenic
      (TG) mice were particularly suited to this examination because they have low
      plasma glucose levels like FR mice. We investigated altered gene expression by FR
      and the effect of low plasma glucose levels caused by genetic manipulation by
      measuring mRNA expression in liver tissues of 4- to 6-mo-old mice with 2.5-4.5 mo
      of FR using microarrays and 4 groups: GLUT4 TG (C57BL/6 background) consumed food
      ad libitum (AL), GLUT4 TG FR, wild-type littermates AL, and wild-type littermates
      FR. The 3 statistical analysis methods commonly indicated that FR altered the
      expression of 1277 genes; however, none of these genes was altered by additional
      GLUT4 expression. In fact, the low plasma glucose level in GLUT4 TG mice did not
      affect gene expression. Some results were confirmed by real-time quantitative RT
      PCR. We conclude that a low plasma glucose level does not contribute to or
      coincide with the effect of FR on gene expression in the liver.

PMID- 15514261
TI  - Mice deficient in methylenetetrahydrofolate reductase exhibit tissue-specific
      distribution of folates.
AB  - Methylenetetrahydrofolate reductase (MTHFR) catalyzes the synthesis of 5
      methyltetrahydrofolate (5-methylTHF), which is used for homocysteine
      remethylation to methionine, the precursor of S-adenosylmethionine (SAM).
      Impairment of MTHFR will increase homocysteine levels and compromise SAM
      dependent methylation reactions. Mild MTHFR deficiency is common in many
      populations due to a polymorphism at bp 677. To assess how impaired MTHFR
      activity affects folate metabolism in various tissues in vivo, we used
      affinity/HPLC with electrochemical detection to analyze the distribution of
      folates in plasma, liver, and brain of Mthfr-deficient mice. The most pronounced
      difference in total folate was observed in plasma. In Mthfr -/- mice, plasma
      total folate levels were approximately 25% of those in wild-type (Mthfr +/+)
      mice. Only 40% of plasma folate in Mthfr -/- mice was comprised of 5-methylTHF,
      compared with at least 80% in the other 2 genotype groups. In liver and brain,
      there were no differences in total folate. However, the proportion of 5-methylTHF
      in both tissues was again markedly reduced in mice with the Mthfr -/- genotype.
      In this genotype group, 5-methylTHF is likely derived from the diet. Our study
      demonstrated reduced total circulatory folate and altered distribution of folate
      derivatives in liver and brain in Mthfr deficiency. Decreased methylfolates and
      increased nonmethylfolates would affect the flux of one-carbon units between
      methylation reactions and nucleotide synthesis. This altered flux has
      implications for several common disorders, including cancer and vascular disease.

PMID- 15514262
TI  - Inhibition of Hedgehog signaling protects adult mice from diet-induced weight
      gain.
AB  - Hedgehog (Hh) signaling plays an important role in embryonic development of many
      tissues, including the gastrointestinal tract. Sonic Hh-and Indian Hh-deficient
      mice die before or soon after birth, precluding further study of this signaling
      pathway in the mature intestine. Maternal transfer of inactivating monoclonal
      antibodies to Hh proteins (anti-Hh moAb) during late stages of embryogenesis or
      to early postnatal mice produced intestinal villous abnormalities, progressive
      runting, and severe malabsorption of dietary fat. In the present study, we sought
      to determine the effect of inhibiting Hh signaling on weight gain and lipid
      absorption in adult mice. Anti-Hh moAb was administered to adult Balb/c mice fed
      either a low-fat, nonpurified diet or a high-fat, semipurified diet, and to adult
      ob/ob mice fed the low-fat, nonpurified diet. Weight gain was significantly
      inhibited by anti-Hh moAb treatment in Balb/C mice fed the high-fat, but not the
      low-fat diet and in ob/ob mice. Further analysis of adult Balb/c mice fed the
      high-fat diet demonstrated that although total lipid absorption was normal, the
      rate of triglyceride absorption was significantly delayed in mice treated with
      anti-Hh moAb and they had significantly increased fecal FFA excretion. Hepatic
      steatosis, found in high-fat fed Balb/c mice treated with the control moAb, was
      abrogated by anti-Hh moAb administration. These findings point to a potential
      role for Hh signaling pathways in diet-induced abnormalities of lipid metabolism.

PMID- 15514263
TI  - Methionine synthase reductase 66A->G polymorphism is associated with increased
      plasma homocysteine concentration when combined with the homozygous
      methylenetetrahydrofolate reductase 677C->T variant.
AB  - Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase
      (MTRR) are important for homocysteine remethylation. This study was designed to
      determine the influence of genetic variants (MTHFR 677C-->T, MTHFR 1298A-->C, and
      MTRR 66A-->G), folate, and vitamin B-12 status on plasma homocysteine in women
      (20-30 y; n = 362). Plasma homocysteine was inversely (P < 0.0001) associated
      with serum folate and plasma vitamin B-12 regardless of genotype. Plasma
      homocysteine was higher (P < 0.05) for women with the MTHFR 677 TT/1298 AA
      genotype combination compared with the CC/AA, CC/AC, and CT/AA genotypes. Women
      with the MTHFR 677 TT/MTRR 66 AG genotype had higher (P < 0.05) plasma
      homocysteine than all other genotype combinations except the TT/AA and TT/GG
      genotypes. There were 5.4-, 4.3-, and 3.8-fold increases (P < 0.001) in risk for
      plasma homocysteine in the top 5, 10, and 20%, respectively, of the homocysteine
      distribution for subjects with the MTHFR 677 TT compared with the CC and CT
      genotypes. Predicted plasma homocysteine was inversely associated with serum
      folate (P = 0.003) and plasma vitamin B-12 (P = 0.002), with the degree of
      correlation dependent on MTHFR 677C-->T genotype. These data suggest that
      coexistence of the MTHFR 677 TT genotype with the MTRR 66A-->G polymorphism may
      exacerbate the effect of the MTHFR variant alone. The potential negative effect
      of combined polymorphisms of the MTHFR and MTRR genes on plasma homocysteine in
      at-risk population groups with low folate and/or vitamin B-12 status, such as
      women of reproductive potential, deserves further investigation.

PMID- 15514264
TI  - Dietary alpha-linolenic acid reduces inflammatory and lipid cardiovascular risk
      factors in hypercholesterolemic men and women.
AB  - Alpha-linolenic acid (ALA) reduces cardiovascular disease (CVD) risk, possibly by
      favorably changing vascular inflammation and endothelial dysfunction.
      Inflammatory markers and lipids and lipoproteins were assessed in
      hypercholesterolemic subjects (n = 23) fed 2 diets low in saturated fat and
      cholesterol, and high in PUFA varying in ALA (ALA Diet) and linoleic acid (LA
      Diet) compared with an average American diet (AAD). The ALA Diet provided 17%
      energy from PUFA (10.5% LA; 6.5% ALA); the LA Diet provided 16.4% energy from
      PUFA (12.6% LA; 3.6% ALA); and the AAD provided 8.7% energy from PUFA (7.7% LA;
      0.8% ALA). The ALA Diet decreased C-reactive protein (CRP, P < 0.01), whereas the
      LA Diet tended to decrease CRP (P = 0.08). Although the 2 high-PUFA diets
      similarly decreased intercellular cell adhesion molecule-1 vs. AAD (-19.1% by the
      ALA Diet, P < 0.01; -11.0% by the LA Diet, P < 0.01), the ALA Diet decreased
      vascular cell adhesion molecule-1 (VCAM-1, -15.6% vs. -3.1%, P < 0.01) and E
      selectin (-14.6% vs. -8.1%, P < 0.01) more than the LA Diet. Changes in CRP and
      VCAM-1 were inversely associated with changes in serum eicosapentaenoic acid
      (EPA) (r = -0.496, P = 0.016; r = -0.418, P = 0.047), or EPA plus
      docosapentaenoic acid (r = -0.409, P = 0.053; r = -0.357, P = 0.091) after
      subjects consumed the ALA Diet. The 2 high-PUFA diets decreased serum total
      cholesterol, LDL cholesterol and triglycerides similarly (P < 0.05); the ALA Diet
      decreased HDL cholesterol and apolipoprotein AI compared with the AAD (P < 0.05).
      ALA appears to decrease CVD risk by inhibiting vascular inflammation and
      endothelial activation beyond its lipid-lowering effects.

PMID- 15514265
TI  - Pinitol supplementation does not affect insulin-mediated glucose metabolism and
      muscle insulin receptor content and phosphorylation in older humans.
AB  - This study assessed the effect of oral pinitol supplementation on oral and
      intravenous glucose tolerances and on skeletal muscle insulin receptor content
      and phosphorylation in older people. Fifteen people (6 men, 9 women; age 66 +/- 8
      y; BMI 27.9 +/- 3.3 kg/m(2); hemoglobin A1c 5.39 +/- 0.46%, mean +/- SD)
      completed a 7-wk protocol. Subjects were randomly assigned to groups that during
      wk 2-7 consumed twice daily either a non-nutritive beverage (Placebo group, n =
      8) or the same beverage with 1000 mg pinitol dissolved into it (Pinitol group, n
      = 7, total dose = 2000 mg pinitol/d). Testing was done at wk 1 and wk 7. In the
      Pinitol group with supplementation, 24-h urinary pinitol excretion increased 17
      fold. The fasting concentrations of glucose, insulin, and C-peptide, and the 180
      min area under the curve for these compounds, in response to oral (75 g) and
      intravenous (300 mg/kg) glucose tolerance challenges, were unchanged from wk 1 to
      wk 7 and were not influenced by pinitol. Also, pinitol did not affect indices of
      hepatic and whole-body insulin sensitivity from the oral glucose tolerance test
      and indices of insulin sensitivity, acute insulin response to glucose, and
      glucose effectiveness from the intravenous glucose tolerance test, estimated
      using minimal modeling. Pinitol did not differentially affect total insulin
      receptor content and insulin receptor phosphotyrosine 1158 and insulin receptor
      phosphotyrosine 1162/1163 activation in vastus lateralis samples taken during an
      oral-glucose-induced hyperglycemic and hyperinsulinemic state. These data suggest
      that pinitol supplementation does not influence whole-body insulin-mediated
      glucose metabolism and muscle insulin receptor content and phosphorylation in
      nondiabetic, older people.

PMID- 15514266
TI  - Supplementation with aromatic amino acids improves leucine kinetics but not
      aromatic amino acid kinetics in infants with infection, severe malnutrition, and
      edema.
AB  - We investigated whether supplementation with an aromatic amino acid (AAA)
      cocktail consisting of 0.5 mmol each of phenylalanine, tryptophan, and tyrosine
      compared with isonitrogenous amounts of alanine (Ala) would improve measures of
      protein kinetics in 14 (8 with AAA, 6 Ala) children with edematous malnutrition
      (aged 6-24 mo) during the infected acute malnourished state. Supplementation
      started immediately after the baseline experiment, 2 d postadmission and
      continued to the end of the acute phase of treatment. The second
      (postsupplementation) experiment was done approximately 12 d postadmission. We
      measured leucine kinetics, phenylalanine and tyrosine fluxes, using an i.g. 8-h
      prime continuous infusion of (2)H(3)-leucine, and an i.v. 6-h prime continuous
      infusion of (13)C-leucine, (2)H(2)-tyrosine, and (2)H(5)-phenylalanine in the fed
      state. Leucine flux tended to be faster (P = 0.06) in the AAA group compared with
      Ala group after supplementation (mean difference +/- SEM): 22.6 +/- 10.9
      micromol/(kg . h). The rate of leucine appearance from protein breakdown [28.1 +/
      9.4 micromol/(kg . h)] and the nonoxidative disposal of leucine [i.e., leucine
      to protein synthesis; 35.4 +/- 12.9 micromol/(kg . h)] were faster (P < 0.02) in
      the AAA group than in the Ala group. There was no significant effect of
      supplementation on leucine splanchnic metabolism, phenylalanine, and tyrosine
      fluxes. These findings are consistent with the hypothesis that the blunting of
      the protein catabolic response to infection in children with edematous
      malnutrition syndrome is due to limited availability of aromatic amino acids.

PMID- 15514267
TI  - Protein source, quantity, and time of consumption determine the effect of
      proteins on short-term food intake in young men.
AB  - The objective of these 4 studies was to describe the effects of protein source,
      time of consumption, quantity, and composition of protein preloads on food intake
      in young men. Young men were fed isolates of whey, soy protein, or egg albumen in
      sweet and flavored beverages (400 mL) and provided a pizza meal 1-2 h later.
      Compared with the water control, preloads (45-50 g) of whey and soy protein, but
      not egg albumen, suppressed food intake at a pizza meal consumed 1 h later. Meal
      energy intake after egg albumen and soy, but not after control or whey
      treatments, was greater when the treatments were given in the late morning (1100
      h) compared with earlier (0830-0910 h). Suppression of food intake after whey
      protein, consumed as either the intact protein or as peptides, extended to 2 h.
      Altering the composition of the soy preload (50 g) by reducing the soy protein
      content to 25 g and by adding 25 g of either glucose or amylose led to a loss in
      suppression of food intake by the preload. Egg albumen, in contrast to whey and
      soy preloads, increased cumulative energy intake (sum of the energy content of
      the preload plus that in the test meal) relative to the control. We conclude that
      protein source, time of consumption, quantity, and composition are all factors
      determining the effect of protein preloads on short-term food intake in young
      men.

PMID- 15514268
TI  - human and bovine milk gangliosides differ in their fatty acid composition.
AB  - Gangliosides are considered bioactive components in human infant nutrition, and
      their fatty acid composition alters their biological effects. We used matrix
      assisted laser desorption/ionization time of flight (MALDI-TOF) MS and GLC to
      analyze the fatty acid composition of the predominant gangliosides, the
      monosialoganglioside GM(3) [sialic acid (Sia) alpha2-3 galactose (Gal) beta1-4
      glucose (Glc) beta1-1 ceramide] and the disialoganglioside GD(3) (Sia alpha2-8
      Sia alpha2-3 Gal beta1-4 Glc beta1-1 ceramide), in pooled human and bovine milk,
      the latter being a source for gangliosides in infant formula. Compared with whole
      milk lipids, both human and bovine milk gangliosides were selectively enriched
      with certain fatty acids, and the fatty acid composition of milk gangliosides in
      the 2 species was significantly different. The amount of long-chain fatty acids
      (> or =20 C atoms) was higher in bovine milk gangliosides (GM(3): 73.71 +/-
      3.39%; GD(3): 79.19 +/- 2.79%) than in human milk gangliosides (GM(3): 51.25 +/-
      0.65%; GD(3): 34.04 +/- 1.80%). Tricosanoic acid (23:0) dominated in bovine milk
      gangliosides (GM(3): 24.05 +/- 1.37%; GD(3): 26.66 +/- 1.24%), whereas it only
      played a minor role in human milk gangliosides (GM(3): 2.88 +/- 0.10%; GD(3):
      1.84 +/- 0.29%). We hypothesized that the differences in the fatty acid
      composition of milk gangliosides result in physiological distinctions between
      breast-fed and formula-fed infants and therefore are of importance for human
      infant nutrition.

PMID- 15514269
TI  - Consumption of high-pressurized vegetable soup increases plasma vitamin C and
      decreases oxidative stress and inflammatory biomarkers in healthy humans.
AB  - Current evidence supports a significant association between fruit and vegetable
      intake and health. In this study, we assessed the effect of consuming a vegetable
      soup "gazpacho" on vitamin C and biomarkers of oxidative stress and inflammation
      in a healthy human population. We also examined the association between vitamin C
      and F(2)-isoprostanes (8-epiPGF(2alpha)), uric acid (UA), prostaglandin E(2)
      (PGE(2)), monocyte chemotactic protein-1 (MCP-1), and the cytokines, tumor
      necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6.
      Gazpacho is a Mediterranean dish defined as a ready-to-use vegetable soup,
      containing approximately 80% crude vegetables rich in vitamin C. Subjects (6 men,
      6 women) enrolled in this study consumed 500 mL/d of gazpacho corresponding to an
      intake of 72 mg of vitamin C. On d 1, subjects consumed the gazpacho in one dose;
      from d 2 until the end of the study, d 14, 250 mL was consumed in the morning and
      250 mL in the afternoon. Blood was collected before drinking the soup (baseline)
      and on d 7 and 14. Baseline plasma vitamin C concentrations did not differ
      between men and women (P = 0.060). Compared with baseline, the vitamin C
      concentration was significantly higher on d 7 and 14 of the intervention in both
      men and women (P < 0.05). Baseline plasma levels of UA and F(2)-isoprostanes were
      higher (P < or = 0.002) in men than in women. The F(2)-isoprostanes decreased on
      d 14 in men and women (P < or = 0.041), and UA decreased in men (P = 0.028). The
      concentrations of vitamin C and 8-epiPGF(2alpha) were inversely correlated (r = 
      0.585, P = 0.0002). Plasma PGE(2) and MCP-1 concentrations decreased in men and
      women (P < or = 0.05) on d 14, but those of TNF-alpha, IL-1beta, and IL-6 did not
      change. Consumption of the vegetable soup decreases oxidative stress and
      biomarkers of inflammation, which indicates that the protective effect of
      vegetables may extend beyond their antioxidant capacity.

PMID- 15514270
TI  - Improvement of nutritional status as assessed by multifrequency BIA during 15
      weeks of refeeding in adolescent girls with anorexia nervosa.
AB  - In patients with anorexia nervosa (AN), an assessment of changes in body
      composition and nutritional status is crucial for adequate nutritional management
      during refeeding therapies. Phase-sensitive multifrequency bioelectrical
      impedance analysis (BIA) is an inexpensive and noninvasive technique with which
      to determine nutritional status and body composition. We investigated 21 female
      adolescents with AN (initial BMI 15.5 +/- 1.1 kg/m(2)) 4 times between wk 3 and
      15 of inpatient refeeding and 19 normal-weight, age-matched female controls. From
      wk 3 to 15, BMI, fat mass, body cell mass (BCM), total body water (TBW),
      intracellular water (ICW) but not extracellular mass (ECM), and extracellular
      water (ECW) increased significantly. Reactance (Xc), phase angle (PhA), and the
      ECM/BCM index as parameters of nutritional status improved significantly in
      patients and no longer differed from controls in wk 15, although the BMI of
      patients was significantly lower than those of controls. Changes in the ECM/BCM
      index were due to accretion of BCM, which was associated with an increase of ICW.
      Multifrequency phase-sensitive BIA seems to be a promising tool for the
      assessment of changes in nutritional status and body composition in patients with
      AN. An individually determined and controlled hyperenergetic diet as part of a
      multidimensional, interdisciplinary treatment program for eating disorders seems
      to quickly improve the nutritional status of AN patients.

PMID- 15514271
TI  - Na2EDTA enhances the absorption of iron and zinc from fortified rice flour in Sri
      Lankan children.
AB  - Rice flour was proposed as a vehicle for iron and zinc fortification in Sri
      Lanka. Although widely consumed, rice flour has not been evaluated as a fortified
      food, and the absorption of minerals including iron and zinc from this flour is
      unknown. Determination of the bioavailability of these nutrients is a critical
      step before commencing a fortification program. We randomly divided 53 Sri Lankan
      schoolchildren ages 6-10 y into 4 groups that consumed a local dish prepared with
      25 g of fortified rice flour labeled with one of the following: 1) (58)FeSO(4) 2)
      (58)FeSO(4) + Na(2)EDTA 3) (58)FeSO(4) + (67)ZnO or, 4) (58)FeSO(4) + Na(2)EDTA +
      (67)ZnO. The levels of iron and zinc were 60 mg/kg; the rice flour also contained
      folate at 2 mg/kg in each group. Na(2)EDTA was added at a Fe:Na(2)EDTA, 1:1 molar
      ratio. A total of 48 children completed the trial. Absorption of (58)Fe from a
      meal was significantly greater (P < 0.01) in the groups administered FeSO(4) +
      Na(2)EDTA (4.7 +/- 3.6%) than in those administered FeSO(4) without Na(2)EDTA
      (2.2 +/- 1.3%). Fractional absorption of zinc was 13.5 +/- 6.0% in the FeSO(4) +
      Na(2)EDTA group and 8.8 +/- 2.0% in the FeSO(4) group (P = 0.037). Although zinc
      absorption was low, our results demonstrated a benefit in using Na(2)EDTA to
      improve both iron and zinc absorption. We conclude that the fortification of rice
      flour is feasible, although additional strategies such as dephytinization or an
      increase in the level of iron and zinc fortification should be considered to
      obtain a higher proportion of the daily requirement of total absorbed iron and
      zinc.

PMID- 15514272
TI  - Low-dose daily iron supplementation for 12 months does not increase the
      prevalence of malarial infection or density of parasites in young Zanzibari
      children.
AB  - Conflicting evidence exists on the possible role of iron supplementation in the
      predisposition to malaria infection or the enhancement of its clinical severity.
      Where anemia prevalence is >40%, current guidelines are to provide low-dose daily
      iron to young children for up to 18 mo. Earlier studies used doses higher than
      the current guidelines, intermittent doses, or have supplemented for durations <
      or = 4 mo. We aimed to assess the effect of low-dose, long-term iron
      supplementation on malaria infection using a double-blind, placebo-controlled,
      randomized design, and to examine possible subgroup effects by season and child
      age. The study was conducted in Pemba Island, Zanzibar, where Plasmodium
      falciparum malaria has year-round high transmission. A community-based sample of
      614 children 4-71 mo old was randomly allocated to 10 mg/d iron or placebo for 12
      mo. Outcome measures were the prevalence and density of malaria infection, which
      was assessed by blood films at monthly intervals. At baseline, 94.4% were anemic
      (hemoglobin < 110 g/L), 48.1% were stunted (height-for-age Z-score less than -2)
      and >80% had malaria-positive blood films. No significant differences in
      malariometric indices were observed between children in the iron-supplemented and
      placebo groups. Parasite density was higher in certain months and in younger
      children, but iron supplementation was not associated with any malarial infection
      outcome in any season or age subgroup. We conclude that in this environment of
      high malaria transmission, daily oral low-dose supplementation of iron for 12 mo
      did not affect the prevalence of malaria infection or parasite density.

PMID- 15514273
TI  - Portal vein caffeine infusion enhances net hepatic glucose uptake during a
      glucose load in conscious dogs.
AB  - We determined whether intraportal caffeine infusion, at rates designed to create
      concentrations similar to that seen with normal dietary intake, would enhance net
      hepatic glucose uptake (NHGU) during a glucose load. Dogs (n = 15) were implanted
      with sampling and infusion catheters as well as flow probes >16 d before the
      studies. After a basal sampling period, dogs were administered a somatostatin
      infusion (0-150 min) as well as intraportal infusions of glucose [18 micromol/(kg
      . min)], basal glucagon [0.5 ng/(kg . min)], and insulin [8.3 pmol/(kg . min)] to
      establish mild hyperinsulinemia. Arterial glucose was clamped at 10 mmol/L with a
      peripheral glucose infusion. At 80 min, either saline (Control; n = 7) or
      caffeine [1.5 micromol/(kg . min); n = 8] was infused into the portal vein.
      Arterial insulin, glucagon, norepinephrine, and glucose did not differ between
      groups. In dogs infused with caffeine, NHGU was significantly higher than in
      controls [21.2 +/- 4.3 vs. 11.2 +/- 1.6 micromol/(kg . min)]. Caffeine increased
      net hepatic lactate output compared with controls [12.5 +/- 3.8 vs. 5.5 +/- 1.5
      micromol/(kg . min)]. These findings indicate that physiologic circulating levels
      of caffeine can enhance NHGU during a glucose load, and the added glucose
      consumed by the liver is in part converted to lactate.

PMID- 15514274
TI  - Decreased protein accretion in pigs with viral and bacterial pneumonia is
      associated with increased myostatin expression in muscle.
AB  - Chronic respiratory infections reduce growth in pigs but protein accretion (PA)
      during an ongoing multifactorial respiratory infection has not been determined,
      and the mechanisms underlying growth inhibition are largely unknown. The
      objectives of this study were to determine whether viral and bacterial pneumonia
      in young pigs decrease PA, increase serum IL-1beta and IL-6, and increase
      myostatin (MSTN) mRNA in biceps femoris and triceps muscles. Mycoplasma
      hyopneumoniae (Mh) or medium was given intratracheally at 4 wk of age, Porcine
      Reproductive and Respiratory Syndrome Virus (PRRSV) or medium was given
      intranasally at 6 wk of age, and pigs were killed 7 or 14 d after PRRSV
      inoculation for body composition analysis. PRRSV but not Mh induced a marked
      increase (P < 0.01) in IL-1beta, IL-6, and MSTN mRNA and a decrease (P < 0.01) in
      food intake, daily weight gain, PA, and lipid accretion. PRRSV also reduced (P <
      0.01) myofiber area in the biceps femoris. Food intake, weight gain, PA, and
      weight of biceps femoris and triceps muscles were negatively correlated (r = -0.4
      to -0.8, P < 0.05) with serum IL-1beta and IL-6 and with MSTN mRNA in muscle.
      These results suggest that the magnitude of increases in inflammatory cytokines
      during a respiratory infection may be predictive of decreases in PA and growth.
      They further suggest that during infection growth of skeletal muscle is limited
      in part by myostatin.

PMID- 15514275
TI  - Calcium and dairy products inhibit weight and fat regain during ad libitum
      consumption following energy restriction in Ap2-agouti transgenic mice.
AB  - We demonstrated previously that dietary calcium suppression of calcitriol reduces
      adipocyte Ca(2+), suppresses lipogenesis, and increases lipid utilization during
      energy restriction. Notably, dairy calcium sources exert markedly greater
      effects. To determine the effects of dietary calcium and dairy products on energy
      partitioning during subsequent refeeding, we induced obesity in aP2-agouti
      transgenic mice with a high-fat/high-sucrose diet, then restricted energy intake
      from a high-calcium (1.3%) diet for 6 wk to induce fat loss, and then provided
      free access to a low-calcium (0.4%) diet or to high-calcium (1.3%) diets that
      utilized either calcium-fortified foods or dairy products (milk or yogurt) for 6
      wk. Refeeding the low-calcium diet caused the regain of all weight and fat,
      whereas all high-calcium diets reduced fat gain by 55% (P < 0.01). All high
      calcium diets stimulated adipose tissue uncoupling protein (UCP)2 and skeletal
      muscle UCP3 expression (P < 0.001) and slightly increased core temperature (P =
      0.136), but only the dairy-based diets elicited a marked (>10-fold, P < 0.001)
      increase in skeletal muscle peroxisome proliferator-activated receptor-alpha
      expression. All 3 high-calcium diets produced significant increases in lipolysis,
      decreases in fatty acid synthase expression and activity, and reduced fat regain
      (P < 0.03), but the 2 dairy-containing high-calcium diets exerted significantly
      greater effects on regain (P < 0.01). Thus, high-Ca diets elicit a shift in
      energy partitioning and reduction of weight gain during refeeding, with dairy Ca
      sources exerting markedly greater effects.

PMID- 15514276
TI  - Iron deficiency negatively affects vertebrae and femurs of rats independently of
      energy intake and body weight.
AB  - The question of whether iron deficiency has direct adverse effects on vertebral
      trabecular bone and long bones was answered by this study. Four groups of female
      weanling rats were fed for 5 wk diets that were 1) control; 2) calcium
      restricted, 1.0 g Ca/kg diet; 3) iron deficient, <8 mg Fe/kg diet; or 4) control,
      pair-fed to the iron-deficient group. Whole body and femur DEXA analysis revealed
      that calcium-restricted and iron-deficient rats had lower bone mineral density
      (BMD) and content (BMC) than pair-fed and control rats. However, pair-fed rats
      also had decreased BMD and BMC compared to control rats. The third lumbar
      trabecular bone microarchitecture in both diet-restricted groups had decreased
      bone volume fraction (BV/TV) and trabecular number and thickness, a less
      favorable structural model index, and increased trabecular separation compared
      with the controls and the pair-fed groups as determined by microcomputer
      tomography. The control and pair-fed groups did not differ from one another,
      suggesting that iron deficiency and calcium restriction affected vertebrae
      independently of food intake and body weight. Finite element analysis revealed
      lower force to compress the vertebrae and lower stiffness but greater von Mises
      stress in calcium-restricted and iron-deficient groups compared to the control
      and pair-fed groups. Urinary deoxypyridinium crosslinks, serum osteocalcin, and
      cholcalciferol were increased in calcium-restricted rats compared to the other 3
      groups. Using micro-CT imaging technology, this study demonstrated
      microarchitectural pathology due to iron deficiency upon vertebral trabecular
      bone compared to the control and pair-fed rats, although not to the same extent
      as severe calcium restriction.

PMID- 15514277
TI  - Route of tracer administration does not affect ileal endogenous nitrogen recovery
      measured with the 15N-isotope dilution technique in pigs fed rapidly digestible
      diets.
AB  - The (15)N-isotope dilution technique ((15)N-IDT), with either pulse-dose oral
      administration or continuous i.v. administration of [(15)N]-l-leucine (carotid
      artery), both at 5 mg/(kg body weight . d), was used to measure ileal (postvalve
      T-cecum cannula) endogenous nitrogen recovery (ENR) in pigs (9 +/- 0.6 kg). Diets
      were cornstarch, enzyme-hydrolyzed casein with no (control) or high (4%) content
      of quebracho extract (Schinopsis spp.) rich in condensed tannins. Blood was
      sampled from a catheter in the external jugular vein. Mean plasma (15)N
      enrichment at d 8-10 was higher (P = 0.0009) after i.v. than after oral
      administration [0.0356 vs. 0.0379 atom% excess (APE)]. Plasma (15)N-enrichment
      for i.v. infused pigs was 0.01117 APE higher (P < 0.0001) and for orally dosed
      pigs 0.0081 APE lower (P < 0.0001) at 11 h postprandial compared with 1 h
      postprandial. Apparent ileal N digestibility was higher (P < 0.0001) for the
      control (85.5%) than for the quebracho diet (69.5%). ENR was calculated from the
      ratio of (15)N-enrichment of plasma and digesta. The ENR for the quebracho diet
      was approximately 300% higher than for the control diet (6.03 vs. 1.94 g/kg dry
      matter intake, P < 0.001). The real N digestibility (92.2 +/- 0.4%) was equal for
      both diets (P = 0.1030) and both tracer methods (P = 0.9730). We concluded that
      oral administration of [(15)N]leucine provides reasonable estimates of ENR in
      pigs fed semipurified diets with high or low content of tannins; however, one
      must be careful in extrapolating this conclusion to studies with other protein
      sources or feeding frequencies.

PMID- 15514278
TI  - Ileal endogenous nitrogen recovery is increased and its amino acid pattern is
      altered in pigs fed quebracho extract.
AB  - Ileal endogenous nitrogen recovery (ENR) in pigs (9 +/- 0.6 kg body weight) was
      estimated simultaneously using the (15)N-isotope dilution technique ((15)N-IDT)
      and the peptide alimentation ultrafiltration (UF) method. Diets were cornstarch,
      enzyme-hydrolyzed casein with no (control) or high (4%) content of quebracho
      extract (Schinopsis spp.) rich in condensed tannins. The amino acid (AA) pattern
      of the ENR was also determined. The ENR of pigs fed the quebracho diet was higher
      (P = 0.0001) than that of pigs fed the control diet [6.00 vs. 1.95 g/kg dry
      matter intake (DMI) for the (15)N-IDT and 5.18 vs. 1.49 g/kg DMI for the UF
      method, respectively]. With the (15)N-IDT, ENR values were 0.44-0.79 g/kg DMI
      (24%) higher (control P = 0.0032, quebracho P = 0.0002) than for the UF method.
      Apparent nitrogen digestibility depended on diet (69.0% quebracho vs. 86.0%
      control, P = 0.0001). Real nitrogen digestibility (RD-N) determined by the UF
      method was higher (P = 0.0001) for the control than for the quebracho diet (91.4
      vs. 88.2%). Corresponding values for the (15)N-IDT did not differ (P = 0.0569)
      between diets (92.8 vs. 91.4%). The (15)N-IDT gave higher values for RD-N of both
      diets (control P = 0.0030, quebracho P = 0.0002) compared with the UF method.
      Endogenous AA recoveries (g/kg DMI) were increased 300% (P = 0.0001) and the AA
      pattern of ENR was changed (P from 0.0001 to 0.7530 for different AA) by the
      quebracho diet. A constant AA-pattern of ENR cannot be assumed. Despite
      limitations of both techniques, the (15)N-IDT and the UF method gave similar
      results with respect to ENR.

PMID- 15514279
TI  - Ferulic acid is quickly absorbed from rat stomach as the free form and then
      conjugated mainly in liver.
AB  - Ferulic acid (FA) is one of the most abundant phenolic antioxidants in the human
      diet. Many studies have documented its beneficial properties. It is therefore
      essential to understand the absorption and metabolism of FA in detail. The
      purpose of this study was to confirm the hypothesis that FA is absorbed in rat
      stomach and metabolized mainly in the liver. We determined the recovery of FA and
      its metabolites (FA sulfate/glucuronides) in rat gastric contents, gastric
      mucosa, portal vein plasma, celiac arterial plasma, bile, and urine after 2.25
      micromol FA was administered in 0.5 mL physiological saline and incubated for 25
      min in situ in the stomach of rats. Within 25 min, 74 +/- 11% of the administered
      FA disappeared from the stomach; later, FA was recovered in both free and
      conjugated forms in plasma, bile, and urine. On the other hand, only free FA was
      detected in the gastric contents and mucosa; it was also detected in the portal
      vein plasma as 49 +/- 5% of the total FA (all forms of FA). However, the
      proportion of free FA in the celiac arterial plasma, bile, and urine decreased to
      5-8%. These results indicate that FA can be quickly absorbed from the rat
      stomach, and then is likely metabolized mainly in the liver. Such novel
      information would be helpful in the use of FA as a nutrient supplement. For
      example, oral administration of FA in capsule form or in a form bonded with sugar
      esters may provide a more appropriate concentration of FA in the circulation,
      which may improve its proposed efficacy in preventing chronic disease.

PMID- 15514280
TI  - A 2-year soy intervention in premenopausal women does not change mammographic
      densities.
AB  - Soy consumption may be related to lower breast cancer risk as assessed by breast
      density. The aims of this 2-y trial were to examine the effects of soy foods and
      lifetime soy intake on mammographic density. After 220 premenopausal women were
      randomly assigned to the intervention or control group, the former group consumed
      2 daily servings of soy foods equivalent to 50 mg of isoflavones and the latter
      consumed their regular diet. The respective dropout rates were 15.6 and 12.6%;
      adherence to the study regimen was high. We assessed lifetime soy intake with a
      questionnaire and measured breast density in screening mammograms obtained at
      baseline and at the end of the trial for 98 intervention and 103 control women
      using a computer-assisted method. None of the mammographic outcomes differed
      significantly by experimental group. The total area of the breast increased and
      the size of the dense areas decreased significantly over time in both groups.
      After 2 y, the mean percentage density had decreased by 2.8 and 4.1% in
      intervention and control women, respectively. Women who reported eating more soy
      during their lives had higher percentage densities than women whose diet included
      little soy; this difference was significant only in Caucasians. Lower soy intake
      during early life and higher soy intake during adulthood predicted a greater
      reduction in the percentage density during the study period. After 2 y of
      intervention, we observed no significant differences in mammographic densities by
      intervention status, but it appears that soy consumption throughout life may have
      some effect on breast density.

PMID- 15514281
TI  - Arachidonic acid in adipose tissue is associated with nonfatal acute myocardial
      infarction in the central valley of Costa Rica.
AB  - Arachidonic acid (AA), a precursor of prothrombotic eicosanoids, is potentially
      atherogenic, but epidemiologic data are scarce. We evaluated the hypothesis that
      increased AA in adipose tissue is associated with increased risk of nonfatal
      acute myocardial infarction (MI), and if so, whether this association is related
      to dietary or adipose tissue linoleic acid. We studied the association between AA
      and MI in 466 cases of a first nonfatal acute MI, matched on age, gender, and
      residence to 466 population controls. Fatty acids (FA) were assessed by GC in
      adipose tissue samples collected from all subjects. Odds ratios (OR) and 95% CI
      were calculated from multivariate conditional logistic regression models.
      Subjects in the highest quintile of adipose tissue AA (0.64% of total FA) had a
      higher risk of nonfatal acute MI than those in the lowest quintile (0.29% of
      total FA), after adjusting for potential confounders including (n-3) and trans
      FAs (OR = 1.94, 95% CI: 1.07, 3.53, P for trend = 0.026). Adipose tissue AA was
      not correlated with dietary AA (r = 0.07), linoleic acid (r = 0.04), or other
      dietary (n-6) FAs, or with adipose tissue linoleic acid (r = -0.07). These data
      suggest that the association between MI and adipose tissue AA is not related to
      dietary intake of (n-6) FAs including linoleic acid. Better understanding of the
      metabolic factors that increase AA in adipose tissue is urgently needed.

PMID- 15514282
TI  - Dietary intake of menaquinone is associated with a reduced risk of coronary heart
      disease: the Rotterdam Study.
AB  - Vitamin K-dependent proteins, including matrix Gla-protein, have been shown to
      inhibit vascular calcification. Activation of these proteins via carboxylation
      depends on the availability of vitamin K. We examined whether dietary intake of
      phylloquinone (vitamin K-1) and menaquinone (vitamin K-2) were related to aortic
      calcification and coronary heart disease (CHD) in the population-based Rotterdam
      Study. The analysis included 4807 subjects with dietary data and no history of
      myocardial infarction at baseline (1990-1993) who were followed until January 1,
      2000. The risk of incident CHD, all-cause mortality, and aortic atherosclerosis
      was studied in tertiles of energy-adjusted vitamin K intake after adjustment for
      age, gender, BMI, smoking, diabetes, education, and dietary factors. The relative
      risk (RR) of CHD mortality was reduced in the mid and upper tertiles of dietary
      menaquinone compared to the lower tertile [RR = 0.73 (95% CI: 0.45, 1.17) and
      0.43 (0.24, 0.77), respectively]. Intake of menaquinone was also inversely
      related to all-cause mortality [RR = 0.91 (0.75, 1.09) and 0.74 (0.59, 0.92),
      respectively] and severe aortic calcification [odds ratio of 0.71 (0.50, 1.00)
      and 0.48 (0.32, 0.71), respectively]. Phylloquinone intake was not related to any
      of the outcomes. These findings suggest that an adequate intake of menaquinone
      could be important for CHD prevention.

PMID- 15514283
TI  - Maternal nutritional status and the risk for orofacial cleft offspring in humans.
AB  - Periconceptional folate and folic acid intake prevents orofacial clefts (OFC) in
      the offspring. It has been suggested that other nutrients also play a role. We
      investigated the preconceptional intake of macronutrients (protein, fat,
      carbohydrate, fiber, and cholesterol), vitamins (vitamin A, retinol, beta
      carotene, ascorbic acid, and alpha-tocopherol), minerals (calcium, phosphorus,
      iron, magnesium, and zinc) and food groups in mothers of OFC children and
      controls. At approximately 14 mo after the index pregnancy, 206 mothers of a
      child with a nonsyndromic OFC and 203 control mothers completed a FFQ on current
      food intake and a general questionnaire. After exclusion of pregnant and
      lactating mothers, mothers who reported a change in diet compared with the
      preconceptional period, and those for whom periconceptional folic acid supplement
      use was unclear, 182 OFC mothers and 173 control mothers were evaluated.
      Macronutrient, vitamin, mineral, and food group intakes were compared. After
      adjustment for energy, quintiles of dietary nutrient intake and odds ratios with
      95% CI were calculated. The preconceptional intake of all macronutrients,
      vitamins, minerals, and food groups with the exception of milk (products),
      potatoes, pies/cookies were lower in OFC mothers than in controls. The energy
      adjusted intakes of vegetable protein, fiber, beta-carotene, ascorbic acid, alpha
      tocopherol, iron, and magnesium were significantly lower in cases compared with
      controls. Increasing intakes of vegetable protein, fiber, ascorbic acid, iron,
      and magnesium decreased OFC risk. In conclusion, a higher preconceptional intake
      of nutrients predominantly present in fruits and vegetables reduces the risk of
      offspring affected by OFC.

PMID- 15514284
TI  - Within- and between-person variation in nutrient intakes of Russian and U.S.
      children differs by sex and age.
AB  - Within- and between-person variation in nutrient intake has been characterized in
      different adult populations, but little is known of country, age, or sex
      differences among children. The objectives of this study were as follows: 1) to
      describe the mean intake, within- and between-individual CV and variance ratios
      of nutrient intake among children ages 9-18 y old in Russia and the United States
      in 1996; 2) to compare the age and sex-related differences in nutrient intake
      variance within and between countries; and 3) to hypothesize about the
      feasibility of using within-individual variance estimates from one nationally
      representative sample to adjust the usual intake distributions in another
      nationally representative sample. Mean intakes of all nutrients except magnesium
      were significantly higher among U.S. children (P < 0.001); within-person
      variation was higher among the U.S. children, possibly indicating greater access
      to a wide array of foods. Strong differentials existed in variance components by
      sex in both countries, although not in the same direction, and differed by age in
      U.S. girls. Ratios of within- to between-person variance in 8 of 11 nutrients
      were lower among Russian (range: 0.9-1.6) than U.S. children (range: 1.4-1.7),
      suggesting that day-to-day bias may not affect Russian dietary recalls as
      strongly as in the United States. Researchers are encouraged to use these
      estimates to conduct sensitivity analyses of usual intake distributions in their
      own data when multiple days of data collection are not feasible.

PMID- 15514285
TI  - Dietary isothiocyanates inhibit Caco-2 cell proliferation and induce G2/M phase
      cell cycle arrest, DNA damage, and G2/M checkpoint activation.
AB  - Benzyl isothiocyanate and phenethyl isothiocyanate, two aromatic phytochemicals
      present in substantial concentrations in edible vegetables of the genus Brassica,
      were investigated for their effects on Caco-2 cell proliferation. Benzyl and
      phenethyl isothiocyanate inhibited DNA synthesis, with 50% inhibitory
      concentrations of 5.1 and 2.4 micromol/L, respectively, and significantly
      increased the doubling times of Caco-2 cells from 32 h to 220 and 120 h,
      respectively. There was no adverse effect of either chemical on cell viability in
      the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, but
      benzyl isothiocyanate and phenethyl isothiocyanate both caused an accumulation of
      cells in the G(2)/M phase of the cell cycle, which was maintained for at least 48
      h in cells synchronized at prometaphase with nocodazole and subsequently treated
      with 10 micromol/L benzyl isothiocyanate or phenethyl isothiocyanate. Both benzyl
      and phenethyl isothiocyanate increased DNA strand breakage, increased
      phosphorylation of the G(2)/M checkpoint enforcer Chk2, and induced p21
      expression. These results suggest that the antiproliferative effects of benzyl
      and phenethyl isothiocyanates toward Caco-2 cells are due at least in part to the
      activation of the G(2)/M DNA damage checkpoint, and that sustained G(2)/M phase
      cell cycle arrest in response to benzyl and phenethyl isothiocyanates may be
      maintained through upregulation of p21. This study indicates that some dietary
      isothiocyanates may exert an antiproliferative effect through activation of the
      G(2)/M DNA damage checkpoint.

PMID- 15514286
TI  - Combined measurement of ferritin, soluble transferrin receptor, retinol binding
      protein, and C-reactive protein by an inexpensive, sensitive, and simple sandwich
      enzyme-linked immunosorbent assay technique.
AB  - The measurement of vitamin A (VA) and iron status is very important in the
      assessment of nutritional deficiencies. The objective of this research was to
      develop a sandwich ELISA technique for the simultaneous measurement of ferritin,
      soluble transferrin receptor, retinol binding protein, and C-reactive protein
      (CRP) as indicators for VA and iron status. The inclusion of CRP as marker of
      infection allows for more accurate interpretation of VA and iron status. This is
      accomplished in a 30-microL serum or plasma sample using an ELISA with different
      capture and detection antibodies and different dilutions of the sample.
      Commercially available clinical serum controls were used for calibration
      purposes. The developed assays were compared to commercially available
      traditional tests. Regression coefficients comparing both assays were better than
      0.84 (P < 0.001). Using a limited sample set, the sandwich ELISA assay produced
      very similar specificity and sensitivity compared to traditional methods when
      common cutoff values were applied. Intra- and interassay variability was between
      5 and 14% for all tests. The cost of the materials for all 5 measurements
      decreases to less than $1/sample if a large number of samples is analyzed. Due to
      the low cost, high throughput, and comparability to traditional tests, this
      procedure has several advantages for assessing VA and iron status in population
      surveys.

PMID- 15514287
TI  - Serum lithium concentration can be used to assess dietary compliance in adults.
AB  - With dietary intervention studies, it is important to ensure that subjects adhere
      to the test diet. Current methods to monitor adherence have substantial
      limitations. Therefore, a dose-response test curve was constructed to determine
      whether small differences in serum Li could be detected in response to ingestion
      of variable Li doses indicative of full or partial dietary compliance. During 3
      separate weeks, subjects consumed a test meal that included a single food
      containing Li citrate daily for 4 d. Doses of 250, 213, or 175 micromol Li were
      used each week to approximate compliance levels of 100, 85, and 70%. On d 4,
      blood samples were taken before and 1, 2, 3, 5, 7, 9, and 24 h after ingesting
      the test meal. Compared with the 100% dose, serum Li was significantly lower at
      all times after the 70% dose and at most times after the 85% dose. Data were
      analyzed to determine a cutoff value so that if a subject's serum Li was below
      that value, they would be declared noncompliant. The probability that a subject
      was declared to be noncompliant when in fact they were compliant was set to 0.05
      (specificity was set to 0.95) and the probability of noncompliance (sensitivity)
      was estimated. Test performance was best in the 3- to 9-h range, for which 90-95%
      of subjects "noncompliant" at the 70% dose were identified. Li can be used as a
      biomarker to determine dietary compliance. Measuring serum Li 3-9 h after the
      last dose provides the highest sensitivity and specificity for noncompliance at
      doses <70%.

PMID- 15514288
TI  - Vitamin D and the dual processes of intestinal calcium absorption.

PMID- 15514289
TI  - Free radicals: the pros and cons of antioxidants. Executive summary report.

PMID- 15514290
TI  - Supplements and tuning up metabolism.

PMID- 15514291
TI  - Mechanisms of pro- and antioxidation.

PMID- 15514293
TI  - Oxidative stress and human genetic variation.

PMID- 15514292
TI  - Iron, free radicals, and oxidative injury.

PMID- 15514294
TI  - Phytochemicals beyond antioxidation.

PMID- 15514295
TI  - Tumor-suppressing effects of antioxidants from tea.

PMID- 15514296
TI  - Antioxidants suppress apoptosis.

PMID- 15514297
TI  - Green tea polyphenols: antioxidative and prooxidative effects.

PMID- 15514298
TI  - Rationale for using high-dose multiple dietary antioxidants as an adjunct to
      radiation therapy and chemotherapy.

PMID- 15514299
TI  - Plasma antioxidant measurements.

PMID- 15514300
TI  - DNA oxidation products, antioxidant status, and cancer prevention.

PMID- 15514301
TI  - Use of biomarkers of oxidative stress in research studies.

PMID- 15514302
TI  - Manganese superoxide dismutase: genetic variation and regulation.

PMID- 15514303
TI  - Consumer perspectives about antioxidants.

PMID- 15514304
TI  - Antioxidant supplement use in cancer survivors and the general population.

PMID- 15514306
TI  - Assessment of antioxidant nutrient intake and status for epidemiologic research.

PMID- 15514305
TI  - Efficacy of dietary antioxidants to prevent oxidative damage and inhibit chronic
      disease.

PMID- 15514307
TI  - Cancer chemotherapy and antioxidants.

PMID- 15514308
TI  - Glutathione and ABC transporters as determinants of sensitivity to oxidative and
      nitrosative stress.

PMID- 15514309
TI  - Antioxidants and radiation therapy.

PMID- 15514310
TI  - Novel functional imaging for tissue oxygen concentration and redox status.

PMID- 15514311
TI  - Prostate cancer prevention.

PMID- 15514312
TI  - Redox-sensitive signaling factors and antioxidants: how tumor cells respond to
      ionizing radiation.

PMID- 15514317
TI  - What has evidence based medicine done for us?

PMID- 15514318
TI  - Evidence based policy making.

PMID- 15514319
TI  - Teaching evidence based medicine.

PMID- 15514320
TI  - Evidence based medicine has come a long way.

PMID- 15514321
TI  - The essence of EBM.

PMID- 15514323
TI  - AMA calls for inquiry into doctors' role in abuse of prisoners.

PMID- 15514324
TI  - Commission unveils shocking pictures for cigarette packs.

PMID- 15514325
TI  - Shortage of emergency doctors will take eight years to rectify.

PMID- 15514326
TI  - NICE guidance on epilepsy recommends specialist diagnosis.

PMID- 15514327
TI  - Doctors need not ventilate baby to prolong his life.

PMID- 15514328
TI  - Law is introduced in US Congress to give access to details of clinical trials.

PMID- 15514329
TI  - Doctor fabricated research while depressed.

PMID- 15514330
TI  - United Nations fails to agree on human cloning.

PMID- 15514332
TI  - BMA continues to oppose assisted suicide and euthanasia.

PMID- 15514339
TI  - Shortage of flu vaccine in US sparks political row.

PMID- 15514342
TI  - What's the evidence that NICE guidance has been implemented? Results from a
      national evaluation using time series analysis, audit of patients' notes, and
      interviews.
AB  - OBJECTIVES: To assess the extent and pattern of implementation of guidance issued
      by the National Institute for Clinical Excellence (NICE). DESIGN: Interrupted
      time series analysis, review of case notes, survey, and interviews. SETTING:
      Acute and primary care trusts in England and Wales. PARTICIPANTS: All primary
      care prescribing, hospital pharmacies; a random sample of 20 acute trusts, 17
      mental health trusts, and 21 primary care trusts; and senior clinicians and
      managers from five acute trusts. MAIN OUTCOME MEASURES: Rates of prescribing and
      use of procedures and medical devices relative to evidence based guidance.
      RESULTS: 6308 usable patient audit forms were returned. Implementation of NICE
      guidance varied by trust and by topic. Prescribing of some taxanes for cancer (P
      < 0.002) and orlistat for obesity (P < 0.001) significantly increased in line
      with guidance. Prescribing of drugs for Alzheimer's disease and prophylactic
      extraction of wisdom teeth showed trends consistent with, but not obviously a
      consequence of, the guidance. Prescribing practice often did not accord with the
      details of the guidance. No change was apparent in the use of hearing aids, hip
      prostheses, implantable cardioverter defibrillators, laparoscopic hernia repair,
      and laparoscopic colorectal cancer surgery after NICE guidance had been issued.
      CONCLUSIONS: Implementation of NICE guidance has been variable. Guidance seems
      more likely to be adopted when there is strong professional support, a stable and
      convincing evidence base, and no increased or unfunded costs, in organisations
      that have established good systems for tracking guidance implementation and where
      the professionals involved are not isolated. Guidance needs to be clear and
      reflect the clinical context.

PMID- 15514343
TI  - Is NICE delivering the goods?

PMID- 15514344
TI  - Collaborative quality improvement to promote evidence based surfactant for
      preterm infants: a cluster randomised trial.
AB  - OBJECTIVE: To test a multifaceted collaborative quality improvement intervention
      designed to promote evidence based surfactant treatment for preterm infants of 23
      29 weeks' gestation. DESIGN: Cluster randomised controlled trial. SETTING AND
      PARTICIPANTS: 114 neonatal intensive care units (which treated 6039 infants of 23
      29 weeks gestation born in 2001). MAIN OUTCOME MEASURES: Process of care
      measures: proportion of infants receiving first surfactant in the delivery room,
      proportion receiving first surfactant more than two hours after birth, and median
      time from birth to first dose of surfactant. Clinical outcomes: death before
      discharge home, and pneumothorax. INTERVENTION: Multifaceted collaborative
      quality improvement advice including audit and feedback, evidence reviews, an
      interactive training workshop, and ongoing faculty support via conference calls
      and email. RESULTS: Compared with those in control hospitals, infants in
      intervention hospitals were more likely to receive surfactant in the delivery
      room (adjusted odds ratio 5.38 (95% confidence interval 2.84 to 10.20)), were
      less likely to receive the first dose more than two hours after birth (adjusted
      odds ratio 0.35 (0.24 to 0.53)), and received the first dose of surfactant sooner
      after birth (median of 21 minutes v 78 minutes, P < 0.001). The intervention
      effect on timing of surfactant was larger for infants born in the participating
      hospitals than for infants transferred to a participating hospital after birth.
      There were no significant differences in mortality or pneumothorax. CONCLUSION: A
      multifaceted intervention including audit and feedback, evidence reviews, quality
      improvement training, and follow up support changed the behaviour of health
      professionals and promoted evidence based practice.

PMID- 15514345
TI  - Variation in use of video assisted thoracic surgery in the United Kingdom.

PMID- 15514346
TI  - Half full or half empty VATS?

PMID- 15514347
TI  - Evidence based guidelines or collectively constructed "mindlines?" Ethnographic
      study of knowledge management in primary care.
AB  - OBJECTIVE: To explore in depth how primary care clinicians (general practitioners
      and practice nurses) derive their individual and collective healthcare decisions.
      DESIGN: Ethnographic study using standard methods (non-participant observation,
      semistructured interviews, and documentary review) over two years to collect
      data, which were analysed thematically. SETTING: Two general practices, one in
      the south of England and the other in the north of England. PARTICIPANTS: Nine
      doctors, three nurses, one phlebotomist, and associated medical staff in one
      practice provided the initial data; the emerging model was checked for
      transferability with general practitioners in the second practice. RESULTS:
      Clinicians rarely accessed and used explicit evidence from research or other
      sources directly, but relied on "mindlines"--collectively reinforced,
      internalised, tacit guidelines. These were informed by brief reading but mainly
      by their own and their colleagues' experience, their interactions with each other
      and with opinion leaders, patients, and pharmaceutical representatives, and other
      sources of largely tacit knowledge. Mediated by organisational demands and
      constraints, mindlines were iteratively negotiated with a variety of key actors,
      often through a range of informal interactions in fluid "communities of
      practice," resulting in socially constructed "knowledge in practice."
      CONCLUSIONS: These findings highlight the potential advantage of exploiting
      existing formal and informal networking as a key to conveying evidence to
      clinicians.

PMID- 15514348
TI  - What is the evidence that postgraduate teaching in evidence based medicine
      changes anything? A systematic review.
AB  - OBJECTIVE: To evaluate the effects of standalone versus clinically integrated
      teaching in evidence based medicine on various outcomes in postgraduates. DESIGN:
      Systematic review of randomised and non-randomised controlled trials and before
      and after comparison studies. DATA SOURCES: Medline, Embase, ERIC, Cochrane
      Library, DARE, HTA database, Best Evidence, BEME, and SCI. STUDY SELECTION: 23
      studies: four randomised trials, seven non-randomised controlled studies, and 12
      before and after comparison studies. 18 studies (including two randomised trials)
      evaluated a standalone teaching method, and five studies (including two
      randomised trials) evaluated a clinically integrated teaching method. MAIN
      OUTCOME MEASURES: Knowledge, critical appraisal skills, attitudes, and behaviour.
      RESULTS: Standalone teaching improved knowledge but not skills, attitudes, or
      behaviour. Clinically integrated teaching improved knowledge, skills, attitudes,
      and behaviour. CONCLUSION: Teaching of evidence based medicine should be moved
      from classrooms to clinical practice to achieve improvements in substantial
      outcomes.

PMID- 15514349
TI  - Integrating evidence based medicine into routine clinical practice: seven years'
      experience at the Hospital for Tropical Diseases, London.
AB  - PROBLEM: Introduction and evaluation of evidence based medicine (EBM) into
      routine hospital practice. STRATEGY FOR CHANGE: Routine EBM meetings introduced
      in 1997. DESIGN: Review of outcomes of meetings from 1997 to 2004, focusing on
      their effect on clinical practice. SETTING: Referral centre for tropical and
      domestic infectious diseases. KEY MEASURE FOR IMPROVEMENT: Outcome of meetings,
      classified as resulting in a change in practice; confirmation or clarification of
      existing practice; identification of a need for more evidence; and outcome
      unclear. EFFECTS OF CHANGE: Examples include a change from inpatient to day case
      treatment of New World cutaneous leishmaniasis; development of guidelines on the
      treatment of coinfection with visceral leishmaniasis and HIV; and identification
      of the need for more data on the efficacy and toxicity of atovaquone-proguanil
      (Malarone) compared with quinine plus sulfadoxine-pyrimethamine (Fansidar) in the
      treatment of uncomplicated falciparum malaria, which resulted in a clinical trial
      being set up. LESSONS LEARNT: Incorporation of EBM meetings into our routine
      practice has resulted in treatment guidelines being more closely based on
      published evidence and improvements to care of patients. Written summaries of the
      meetings are important to facilitate change.

PMID- 15514350
TI  - The fool wonders, the wise (women) ask...about tropical diseases in their
      practice.

PMID- 15514351
TI  - How does evidence based guidance influence determinations of medical negligence?

PMID- 15514352
TI  - Evaluating the teaching of evidence based medicine: conceptual framework.

PMID- 15514353
TI  - A conceptual framework may be of limited value.

PMID- 15514354
TI  - "Evidence of me" in evidence based medicine?

PMID- 15514355
TI  - Putting evidence into practice: how middle and low income countries "get it
      together".

PMID- 15514357
TI  - Compulsory registration of clinical trials: publicly funded national register of
      trials would be best in the United Kingdom.

PMID- 15514356
TI  - Inappropriate use of randomised trials to evaluate complex phenomena: case study
      of vaginal breech delivery.

PMID- 15514358
TI  - Truth and evidence based medicine: spin is everything.

PMID- 15514359
TI  - General practitioners say that evidence based information is changing practice.

PMID- 15514360
TI  - Pressures are growing to publish clinical trials.

PMID- 15514361
TI  - Compulsory registration of clinical trials: under-reporting is not an option.

PMID- 15514362
TI  - Compulsory registration of clinical trials: maybe European research should be
      protected.

PMID- 15514363
TI  - Biopsy of potentially operable hepatic colorectal metastases is not useless but
      dangerous.

PMID- 15514364
TI  - Adenotonsillectomy in children with mild symptoms: watchful waiting is
      appropriate.

PMID- 15514365
TI  - Adenotonsillectomy in children with mild symptoms: watchful waiting may deny
      children opportunity for development.

PMID- 15514366
TI  - Email consultations in health care: patients need to be given a choice.

PMID- 15514367
TI  - Email consultations in health care: set your auto reply to "no".

PMID- 15514368
TI  - Transradial angiography may deleteriously affect patency of radial artery grafts.

PMID- 15514369
TI  - Quality of life of postmenopausal women in the Arimidex, Tamoxifen, Alone or in
      Combination (ATAC) Adjuvant Breast Cancer Trial.
AB  - PURPOSE: To determine the quality of life (QoL) of women participating in the
      Arimidex, Tamoxifen, Alone or in Combination (ATAC) Adjuvant Breast Cancer Trial
      during the first 2 years of treatment. PATIENTS AND METHODS: A total of 1,021
      women were enrolled onto the QoL subprotocol. All had completed primary treatment
      (surgery +/- radiotherapy +/- chemotherapy) and were to receive 5 years of
      adjuvant treatment with anastrozole (n = 335), tamoxifen (n = 347), or a
      combination (n = 339) of both. Patients completed the Functional Assessment of
      Cancer Therapy-Breast (FACT-B) plus endocrine subscale (ES) at baseline and 3, 6,
      12, 18, and 24 months, or until disease recurrence. The primary end point was the
      FACT-B Trial Outcome Index (TOI). The secondary end point was the ES total score.
      Analyses of individual endocrine symptoms were also explored. RESULTS:
      Questionnaire completion approximated 85% of assessments available for analysis.
      Overall QoL for all groups improved from baseline during the 2-year period. There
      were no significant differences in TOI or ES scores across treatment groups.
      Endocrine symptoms increased between baseline and 3 months for all groups and
      stabilized thereafter. There were some small differences in side effect profiles.
      Compared with patients receiving tamoxifen only, patients receiving anastrozole
      only reported significantly fewer cold sweats and vaginal discharge, yet more
      vaginal dryness, painful intercourse, and loss of sexual interest. CONCLUSION:
      Two years of treatment with anastrozole, tamoxifen, or the combination had a
      similar overall QoL impact, showing gradual improvement over time. Endocrine
      related symptoms for all three arms worsened initially and recovered partially
      during 2 years. The different symptoms experienced may assist in decision making
      about treatment and supportive care needs.

PMID- 15514370
TI  - Phase II study of fenretinide (NSC 374551) in adults with recurrent malignant
      gliomas: A North American Brain Tumor Consortium study.
AB  - PURPOSE: Fenretinide induces apoptosis in malignant gliomas in vitro. This two
      stage phase II trial was conducted to determine the efficacy of fenretinide in
      adults with recurrent malignant gliomas. PATIENTS AND METHODS: Twenty-two
      patients with anaplastic gliomas (AG) and 23 patients with glioblastoma (GBM)
      whose tumors had recurred after radiotherapy and no more than two chemotherapy
      regimens were enrolled. Fenretinide was given orally on days 1 to 7 and 22 to 28
      in 6-week cycles in doses of 600 or 900 mg/m(2) bid. RESULTS: Six of 21 (29%)
      patients in the AG arm and two of 23 (9%) patients in the GBM arm had stable
      disease at 6 months. One patient with AG treated at 900 mg/m(2) bid dosage had a
      partial radiologic response. Median progression-free survival (PFS) was 6 weeks
      for the AG arm and 6 weeks for the GBM arm. PFS at 6 months was 10% for the AG
      arm and 0% for the GBM arm. Grade 1 or 2 fatigue, dryness of skin, anemia, and
      hypoalbuminemia were the most frequent toxicities reported. The trial was closed
      after the first stage because of the inadequate activity at the fenretinide doses
      used. The first-administration mean plasma C(max) for fenretinide was 832 +/- 360
      ng/mL at the 600 mg/m(2) bid dosage and 1,213 +/- 261 ng/mL at the 900 mg/m(2)
      bid dosage. CONCLUSION: Fenretinide was inactive against recurrent malignant
      gliomas at the dosage used in this trial. However, additional studies using
      higher doses of the agent are warranted based on the tolerability of the agent
      and the potential for activity of a higher fenretinide dosage, as suggested in
      this trial.

PMID- 15514371
TI  - Dose escalation studies of cytarabine, daunorubicin, and etoposide with and
      without multidrug resistance modulation with PSC-833 in untreated adults with
      acute myeloid leukemia younger than 60 years: final induction results of Cancer
      and Leukemia Group B Study 9621.
AB  - PURPOSE: P-glycoprotein (Pgp) is strongly inhibited by PSC-833. A chemotherapy
      dose-escalation study was performed with PSC-833 in patients younger than 60
      years with untreated acute myeloid leukemia. Clinical rather than pharmacokinetic
      end points were used to develop two induction therapies containing drugs
      susceptible to Pgp-mediated efflux and associated with comparable toxicities at
      the maximum-tolerated doses. PATIENTS AND METHODS: A total of 410 patients were
      enrolled. Fifteen induction regimens containing variable doses of daunorubicin
      (DNR) and etoposide (ETOP) and fixed doses of cytarabine were evaluated with
      (ADEP) or without (ADE) a fixed dose of PSC-833. RESULTS: Doses selected for
      phase III testing were DNR 90 mg/m(2) and ETOP 100 mg/m(2) in ADE, and DNR and
      ETOP each 40 mg/m(2) in ADEP. Intolerable mucosal toxicity occurred at higher
      doses of ADEP. Although the design of this study precludes direct comparisons,
      there was an apparent advantage for receiving ADEP with respect to disease-free
      and overall survival in patients < or = 45 years old, despite the significantly
      lower doses of DNR and ETOP given in ADEP compared with ADE. CONCLUSION: A large
      clinical data set was used to develop induction regimens containing two drugs
      susceptible to Pgp-mediated efflux, with and without an inhibitor of Pgp
      function. The chosen doses have comparable antileukemia activity and toxicity,
      making them suitable for use in a phase III comparative study of induction
      chemotherapy for patients with acute myeloid leukemia younger than 60 years. That
      trial will also clarify whether patients < or = 45 years old are especially
      likely to benefit from Pgp inhibition during induction therapy.

PMID- 15514372
TI  - Why cancer patients enter randomized clinical trials: exploring the factors that
      influence their decision.
AB  - PURPOSE: Few interventions have been designed and tested to improve recruitment
      to clinical trials in oncology. The multiple factors influencing patients'
      decisions have made the prioritization of specific interventions challenging. The
      present study was undertaken to identify the independent predictors of a cancer
      patient's decision to enter a randomized clinical trial. METHODS: A list of
      factors from the medical literature was augmented with a series of focus groups
      involving cancer patients, physicians, and clinical research associates (CRAs). A
      series of questionnaires was developed with items based on these factors and were
      administered concurrently to 189 cancer patients, their physicians, and CRAs
      following the patient's decision regarding trial entry. Forward logistic
      regression modeling was performed using the items significantly correlated (by
      univariate analysis) with the decision to enter a clinical trial. RESULTS: A
      number of items were significantly correlated with the patient's decision. In the
      multivariate logistic regression model, the patient's perception of personal
      benefit was the most important, with an odds ratio (OR) of 3.08 (P < .05). CRA
      related items involving supportive aspects of the decision-making process were
      also important. These included whether the CRA helped with the decision (OR =
      1.71; P < .05), and whether the decision was hard for the patient to make (OR =
      0.52; P < .05). CONCLUSION: Strategies that better address the potential benefits
      of trial entry may result in improved accrual. Interventions or aids that focus
      on the supportive aspects of the decision-making process while respecting the
      need for information and patient autonomy may also lead to meaningful
      improvements in accrual.

PMID- 15514373
TI  - Randomized multicenter phase II trial of a biweekly regimen of fluorouracil and
      leucovorin (LV5FU2), LV5FU2 plus cisplatin, or LV5FU2 plus irinotecan in patients
      with previously untreated metastatic gastric cancer: a Federation Francophone de
      Cancerologie Digestive Group Study--FFCD 9803.
AB  - PURPOSE: To determine the efficacy and safety of a biweekly regimen of leucovorin
      (LV) plus fluorouracil (FU) alone or in combination with cisplatin or irinotecan
      in patients with previously untreated metastatic gastric adenocarcinoma and to
      select the best arm for a phase III study. PATIENTS AND METHODS: One hundred
      thirty-six patients (two were ineligible) were enrolled onto the randomized
      multicenter phase II trial. Patients received LV 200 mg/m(2) (2-hour infusion)
      followed by FU 400 mg/m(2) (bolus) and FU 600 mg/m(2) (22-hour continuous
      infusion) on days 1 and 2 every 14 days (LV5FU2; arm A), LV5FU2 plus cisplatin 50
      mg/m(2) (1-hour infusion) on day 1 or 2 (arm B), or LV5FU2 plus irinotecan 180
      mg/m(2) (2-hour infusion) on day 1 (arm C). RESULTS: The overall response rates,
      which were confirmed by an independent expert panel, were 13% (95% CI, 3.4% to
      23.3%), 27% (95% CI, 14.1% to 40.4%), and 40% (95% CI, 25.7% to 54.3%) for arms
      A, B, and C, respectively. Median progression-free survival and overall survival
      times were 3.2 months (95% CI, 1.8 to 4.6 months) and 6.8 months (95% CI, 2.6 to
      11.1 months) with LV5FU2, respectively; 4.9 months (95% CI, 3.5 to 6.3 months)
      and 9.5 months (95% CI, 6.9 to 12.2 months) with LV5FU2-cisplatin, respectively;
      and 6.9 months (95% CI, 5.5 to 8.3 months) and 11.3 months (95% CI, 9.3 to 13.3
      months) with LV5FU2-irinotecan, respectively. CONCLUSION: Of the three regimens
      tested, the combination of LV5FU2-irinotecan is the most promising and will be
      assessed in a phase III trial.

PMID- 15514374
TI  - Carboplatin/paclitaxel or carboplatin/vinorelbine followed by accelerated
      hyperfractionated conformal radiation therapy: report of a prospective phase I
      dose escalation trial from the Carolina Conformal Therapy Consortium.
AB  - PURPOSE: To prospectively determine the maximum-tolerated dose of accelerated
      hyperfractionated conformal radiotherapy (RT; 1.6 Gy bid) for unresectable
      locally advanced lung cancer (IIB to IIIA/B) following induction
      carboplatin/paclitaxel (C/T) or carboplatin/vinorelbine (C/N). METHODS: Induction
      chemotherapy, C/T or C/N, was followed by escalating doses of conformally-planned
      RT (73.6 to 86.4 Gy in 6.4-Gy increments). Concurrent boost methods delivered 1.6
      and 1.25 Gy bid to the gross and clinical target volumes, respectively. RESULTS:
      Between November 1997 and February 2002, 44 patients were enrolled (median age,
      59 years; 59% male; stage III, 98%; median tumor size, 4 cm). Thirty-nine
      patients completed induction chemotherapy: 19 had a partial response, seven
      progressed, 15 had no response, and three were not assessable. Chemotherapy
      associated toxicities were similar in the two chemotherapy groups. The incidence
      of grade > or = 3 RT-induced toxicity was 1/13, 2/14, and 4/12 at 73.6, 80, and
      86.4 Gy, respectively, thus defining the maximum tolerated dose at approximately
      80 Gy. Toxicities were in both lung and esophagus and were similar in the two
      chemotherapy arms. With a median followup of 34 months in the survivors, the
      actuarial 2-year survival was 47%, the median survival was 18 months. Fifteen
      patients had tumor relapse: 5 local failures in the high-dose volume, 2 regional
      failures outside of the high-dose volume, and 8 distant metastases. CONCLUSION:
      High-dose conformal twice-daily radiation therapy to approximately 80 Gy appears
      tolerable in well-selected patients with unresectable lung cancer following
      either C/T or C/N. Dose-limiting toxicities are mainly pulmonary and esophageal.

PMID- 15514375
TI  - Induction and concurrent chemotherapy with high-dose thoracic conformal radiation
      therapy in unresectable stage IIIA and IIIB non-small-cell lung cancer: a dose
      escalation phase I trial.
AB  - PURPOSE: Local control rates at conventional radiotherapy doses (60 to 66 Gy) are
      poor in stage III non-small-cell lung cancer (NSCLC). Dose escalation using three
      dimensional thoracic conformal radiation therapy (TCRT) is one strategy to
      improve local control and perhaps survival. PATIENTS AND METHODS: Stage III NSCLC
      patients with a good performance status (PS) were treated with induction
      chemotherapy (carboplatin area under the curve [AUC] 5, irinotecan 100 mg/m(2),
      and paclitaxel 175 mg/m(2) days 1 and 22) followed by concurrent chemotherapy
      (carboplatin AUC 2 and paclitaxel 45 mg/m(2) weekly for 7 to 8 weeks) beginning
      on day 43. Pre- and postchemotherapy computed tomography scans defined the
      initial clinical target volume (CTV(I)) and boost clinical target volume
      (CTV(B)), respectively. The CTV(I) received 40 to 50 Gy; the CTV(B) received
      escalating doses of TCRT from 78 Gy to 82, 86, and 90 Gy. The primary objective
      was to escalate the TCRT dose from 78 to 90 Gy or to the maximum-tolerated dose.
      RESULTS: Twenty-nine patients were enrolled (25 assessable patients; median age,
      59 years; 62% male; 45% stage IIIA; 38% PS 0; and 38% > or = 5% weight loss).
      Induction CIP was well tolerated (with filgrastim support) and active (partial
      response rate, 46.2%; stable disease, 53.8%; and early progression, 0%). The TCRT
      dose was escalated from 78 to 90 Gy without dose-limiting toxicity. The primary
      acute toxicity was esophagitis (16%, all grade 3). Late toxicity consisted of
      grade 2 esophageal stricture (n = 3), bronchial stenosis (n = 2), and fatal
      hemoptysis (n = 2). The overall response rate was 60%, with a median survival
      time and 1-year survival probability of 24 months and 0.73 (95% CI, 0.55 to
      0.89), respectively. CONCLUSION Escalation of the TCRT dose from 78 to 90 Gy in
      the context of induction and concurrent chemotherapy was accomplished safely in
      stage III NSCLC patients.

PMID- 15514376
TI  - Role of lung transplantation in the treatment of bronchogenic carcinomas for
      patients with end-stage pulmonary disease.
AB  - PURPOSE: To determine the role of lung transplantation in the treatment of
      patients presenting with bronchogenic carcinoma and end-stage lung disease.
      METHODS: An international survey was conducted to determine the outcome of
      patients with bronchogenic carcinoma in the explanted lung at the time of
      transplantation. A group of 69 patients was collected from 33 centers. RESULTS:
      Twenty-six patients underwent 29 lung transplantations for advanced multifocal
      bronchioloalveolar carcinoma (BAC) as the primary indication for transplantation,
      and 13 developed a recurrence, with an overall 5-year actuarial survival of 39%.
      Incidental bronchogenic carcinomas classified as stage I (n = 22), II (n = 12),
      and III (n = 2), or as incidental multifocal BAC (n = 7), were found in the
      explanted lung of the remaining 43 patients. The 5-year actuarial survival was
      51% in patients with stage I carcinomas, and was significantly better than for
      patients with stage II and III carcinomas (survival of 14%) or with incidental
      multifocal BAC (survival of 23%). Time from transplantation to recurrence and
      from recurrence to death was significantly longer in patients with multifocal BAC
      than in patients with other types of bronchogenic carcinoma. In addition, the
      site of recurrence was limited to the transplanted lung in 88% of the patients
      with multifocal BAC, whereas it was always widespread in patients with other
      types of bronchogenic carcinoma. CONCLUSION: This study demonstrates that long
      term survival can be achieved after lung transplantation in patients with stage I
      bronchogenic carcinoma or with advanced multifocal BAC.

PMID- 15514377
TI  - Accuracy of whole-body dual-modality fluorine-18-2-fluoro-2-deoxy-D-glucose
      positron emission tomography and computed tomography (FDG-PET/CT) for tumor
      staging in solid tumors: comparison with CT and PET.
AB  - PURPOSE: To assess the accuracy of positron emission tomography/computed
      tomography (PET/CT) when staging different malignant diseases. PATIENTS AND
      METHODS: This was a retrospective, blinded, investigator-initiated study of 260
      patients with various oncological diseases who underwent fluorine-18-2-fluoro-2
      deoxy-d-glucose PET/CT for tumor staging. CT images alone, PET images alone, PET
      + CT data viewed side by side, and fused PET/CT images were evaluated separately
      according to the tumor-node-metastasis system. One hundred forty patients with
      tumors not staged according to the tumor-node-metastasis system or a lack of
      reference standard were excluded from data analysis; 260 patients were included.
      Diagnostic accuracies were determined for each of the four image sets.
      Histopathology and a clinical follow-up of 311 (+/- 125) days served as standards
      of reference. RESULTS: PET/CT proved significantly more accurate in assessing
      tumor-node-metastasis system stage compared with CT alone, PET alone, and side-by
      side PET + CT (P < .0001). Of 260 patients, 218 (84%; 95% CI, 79% to 88%) were
      correctly staged with PET/CT, 197 (76%; 95% CI, 70% to 81%) with side-by-side PET
      + CT, 163 (63%; 95% CI, 57% to 69%) with CT alone, and 166 (64%; 95% CI, 58% to
      70%) with PET alone. Combined PET/CT had an impact on the treatment plan in 16,
      39, and 43 patients when compared with PET + CT, CT alone, and PET alone,
      respectively. CONCLUSION: Tumor staging with PET/CT is significantly more
      accurate than CT alone, PET alone, and side-by-side PET + CT. This diagnostic
      advantage translates into treatment plan changes in a substantial number of
      patients.

PMID- 15514378
TI  - Effect of pregnancy on survival in women with cutaneous malignant melanoma.
AB  - PURPOSE: An adverse influence of pregnancy on the risk of death in women with
      cutaneous melanoma was suggested historically by anecdotal reports. Previous
      studies included small numbers of women observed for short periods. METHODS:
      Using data from the Swedish National and Regional Registries, we performed a
      retrospective cohort study of all Swedish women who were diagnosed with cutaneous
      melanoma during their reproductive period, from January 1, 1958, to December 31,
      1999. The relationship between pregnancy status at the diagnosis of melanoma and
      overall survival was examined in multivariable proportional-hazards models.
      RESULTS: The cohort comprised 185 women (3.3%) diagnosed with melanoma during
      pregnancy and 5,348 (96.7%) women of the same childbearing age diagnosed with
      melanoma while not pregnant. There was no statistically significant difference in
      overall survival between pregnant and nonpregnant groups (log-rank chi(2)1[r] =
      0.84, P = .361). Pregnancy status at the time of diagnosis of melanoma was not
      related to survival in a multivariable Cox model in the 2,101 women (hazard ratio
      for death in the pregnant group was 1.08; 95% CI, 0.60 to 1.93). In the
      multivariable analysis, pregnancy status after diagnosis of melanoma was not a
      significant predictor of survival (hazard ratio for death in women who had
      pregnancy subsequent to the diagnosis of melanoma was 0.58; 95% CI, 0.32 to
      1.05). CONCLUSION: The survival of pregnant women with melanoma is not worse than
      the survival of nonpregnant women with melanoma. Pregnancy subsequent to the
      diagnosis of primary melanoma was not associated with an increased risk of death.

PMID- 15514379
TI  - Impact of ulceration in stages I to III cutaneous melanoma as staged by the
      American Joint Committee on Cancer Staging System: an analysis of the German
      Central Malignant Melanoma Registry.
AB  - PURPOSE: In 2001, the new American Joint Committee on Cancer classification of
      cutaneous melanoma (CM) introduced ulceration of the primary melanoma as a new
      key parameter being represented in respective subcategories of the tumor (T)
      classification. The present study was performed to validate the prognostic
      significance of ulceration in relation to T thickness and clinical stages of CM
      (stages I to III). PATIENTS AND METHODS: Patients (N = 15,158) with incident
      invasive primary nonmetastatic CM and follow-up data recorded between 1976 and
      2000 by the German Central Malignant Melanoma Registry were investigated using
      survival analysis to evaluate prognostic factors such as T thickness, level of
      invasion, body site, histologic subtype, ulceration, regression, age, and sex.
      RESULTS: Comparisons of survival probabilities according to the Kaplan-Meier
      method between ulcerated and nonulcerated CM were not statistically significant
      for subgroups with T thickness < or = 1 mm and more than 4.00 mm (P = .2601 and P
      = .0699, respectively) but were significant for T thickness of 1.01 to 2.00 mm
      and 2.01 to 4.00 mm (P < .0001 for both). This result was confirmed in the
      multivariate analysis. For stage III CM, the impact of ulceration on overall
      survival was statistically significant in the bivariate Cox model (P = .0111) but
      not in the multivariate Cox model (P = .0522). CONCLUSION: Whereas ulceration
      seems to have a negative impact on the prognosis of patients with stages T2 and
      T3, a potential influence for patients with stages T1 and T4 could not be
      established. If factors of the primary CM were to be taken into consideration to
      judge prognosis of stage III CM, T thickness but not ulceration should be the
      focus.

PMID- 15514380
TI  - Early deaths and treatment-related mortality in children undergoing therapy for
      acute myeloid leukemia: analysis of the multicenter clinical trials AML-BFM 93
      and AML-BFM 98.
AB  - PURPOSE: The rates of early death (ED) and treatment-related mortality (TRM) are
      unacceptably high in children undergoing intensive chemotherapy for acute myeloid
      leukemia (AML). Better strategies of supportive care might help to improve
      overall survival in these children. PATIENTS AND METHODS: In a retrospective
      study, we analyzed incidence, clinical features, and risk factors for lethal
      complications of 901 children enrolled onto the multicenter trials Acute Myeloid
      Leukemia-Berlin-Frankfurt-Muenster (AML-BFM) 93 and AML-BFM 98. RESULTS: One
      hundred four patients (11.5%) enrolled onto the clinical trials AML-BFM 93 and
      AML-BFM 98 died shortly after diagnosis or as a result of treatment-related
      complications. Thirty-two patients (3.5%) died before (six patients) or during
      (26 patients) the first 14 days of treatment, mainly as a result of bleeding or
      leukostasis. Low performance status, hyperleukocytosis, and French-American
      British type M5 were the main risk factors for a lethal event before day 15.
      After day 15, the predominant causes of death were complications caused by
      infections, particularly bacterial and fungal infections. The incidence of lethal
      infections was highest during induction therapy and decreased thereafter. When
      comparing both clinical trials, significantly fewer patients died within the
      first 6 weeks in AML-BFM 98 than in AML-BFM 93 (14 [3.5%] of 430 patients v 35
      [7.4%] of 471 patients; P = .01). CONCLUSION: To reduce the high incidence of ED
      and TRM in children with AML, early diagnosis and adequate treatment of
      complications are needed. Children with AML should be treated in specialized
      pediatric cancer centers only. Prophylactic and therapeutic regimens for better
      treatment management of bleeding disorders and infectious complications have to
      be assessed in future trials to ultimately improve overall survival in children
      with AML.

PMID- 15514381
TI  - Phase I and pharmacokinetic study of thalidomide with carboplatin in children
      with cancer.
AB  - PURPOSE: Tumor growth and metastasis is believed to depend on the tumor's ability
      to induce neovascularization. Recent studies have indicated that thalidomide
      inhibits angiogenesis. We performed a phase I and pharmacokinetic study of
      thalidomide with carboplatin in children with refractory solid tumors. PATIENTS
      AND METHODS: Carboplatin was administered as a single intravenous dose once every
      21 days at a target area under the concentration-time curve of 6 mg/mL.min.
      Thalidomide was administered daily by mouth. The initial dose level was 100
      mg/m(2)/d with intrapatient dose escalation to a maximum dose of 300 mg/m(2)/d.
      The next cohort of patients started at a dose of 300 mg/m(2)/d, with intrapatient
      dose escalation to a maximum dose of 500 mg/m(2)/d. Standard response and adverse
      event criteria were used. Serial blood samples for thalidomide pharmacokinetics
      studies were obtained after the first dose. RESULTS: Twenty-two patients received
      56 cycles of therapy. The maximum tolerated thalidomide dose was 400 mg/m(2)/d.
      The dose-limiting toxicity was somnolence. There were no objective responses.
      Thalidomide's apparent clearance was 55 +/- 16 mL/min/m(2) and the terminal half
      life was 5.9 +/- 2.8 hours. There was no evidence of dose-dependent
      pharmacokinetics in the narrow range studied. CONCLUSION: Thalidomide at a dose
      of 400 mg/m(2)/d can be safely administered to children with solid tumors in
      combination with carboplatin. Somnolence is the major toxicity. In addition, we
      have characterized the pharmacokinetic behavior of thalidomide in children. This
      study can serve as the basis for future investigation of thalidomide as an
      anticancer agent in children.

PMID- 15514382
TI  - Cancer consultation preparation package: changing patients but not physicians is
      not enough.
AB  - PURPOSE: This study evaluated a cancer consultation preparation package (CCPP)
      designed to facilitate patient involvement in the oncology consultation. PATIENTS
      AND METHODS: A total of 164 cancer patients (67% response rate) were randomly
      assigned to receive the CCPP or a control booklet at least 48 hours before their
      first oncology appointment. The CCPP included a question prompt sheet, booklets
      on clinical decision making and patient rights, and an introduction to the
      clinic. The control booklet contained only the introduction to the clinic.
      Physicians were blinded to which intervention patients received. Patients
      completed questionnaires immediately after the consultation and 1 month later.
      Consultations were audiotaped, transcribed verbatim, and coded. RESULTS: All but
      one patient read the information. Before the consultation, intervention patients
      were significantly more anxious than were controls (mean, 42 v 38; P = .04);
      however anxiety was equivalent at follow-up. The CCPP was reported as being
      significantly more useful to family members than the control booklet (P = .004).
      Patients receiving the intervention asked significantly more questions (11 v
      seven questions; P = .005), tended to interrupt the physician more (1.01 v 0.71
      interruptions; P = .08), and challenged information significantly more often
      (twice v once; P = .05). Patients receiving the CCPP were less likely to achieve
      their preferred decision making style (22%) than were controls (35%; P = .06).
      CONCLUSION: This CCPP influences patients' consultation behavior and does not
      increase anxiety in the long-term. However, this intervention, without physician
      endorsement, reduced the percentage of patients whose preferred involvement in
      decision making was achieved.

PMID- 15514383
TI  - Phase II study of activated charcoal to prevent irinotecan-induced diarrhea.
AB  - PURPOSE: The dose-limiting toxicity of irinotecan (CPT-11; Camptosar) is delayed
      onset diarrhea, with an incidence at the grade 3 to 4 level of 20% to 35%. SN38,
      its active moiety, is responsible by a direct effect on mucosal topoisomerase-I.
      The aim of this study was to assess whether activated charcoal (AC), possibly by
      adsorbing free lumenal SN38, can reduce irinotecan-induced diarrhea (CID) and
      optimize its dose-intensity. PATIENTS AND METHODS: Patients with advanced
      colorectal cancer receiving irinotecan 125 mg/m(2) intravenously once a week for
      4 weeks every 6 weeks were studied. In cycle 1, patients received irinotecan plus
      AC (5 mL aqueous Charcodote [1,000 mg AC] plus 25 mL water) given the evening
      before the irinotecan dose and then tid for 48 hours after the dose. In cycle 2,
      no AC was given. National Cancer Institute Common Toxicity Criteria diarrhea
      grade, irinotecan dose-intensity, and loperamide consumption were recorded
      prospectively in both cycles. RESULTS: Twenty-eight patients had completed cycle
      1 with AC; 24 subsequently completed cycle 2 without AC. Grade 3 to 4 diarrhea
      was 7.1% v 25%, and grade 0 diarrhea was 46.4% v 20.8% in cycles 1 and 2,
      respectively. Median percent planned dose delivered was 98% v 70% in cycles 1 and
      2, respectively. In cycles 1 and 2, respectively, 25% v 54% patients took more
      than 10 loperamide tablets. AC was well tolerated with excellent compliance.
      CONCLUSION: The administration of AC with irinotecan reduced the incidence of
      grade 3 to 4 diarrhea and antidiarrheal medication consumption and increased
      irinotecan dose-intensity. Prophylactic AC may have a role in reducing dose
      limiting CID and optimizing irinotecan therapy.

PMID- 15514384
TI  - Efficacy of coenzyme Q10 for improved tolerability of cancer treatments: a
      systematic review.
AB  - PURPOSE: The aim of this systematic review was to summarize and evaluate the
      evidence available for oral supplementation with coenzyme Q10 (CoQ10) to improve
      the tolerability of cancer treatments. MATERIALS AND METHODS: Searches for all
      published and unpublished controlled trials were carried out on seven databases.
      Manufacturers of CoQ10 were identified and contacted. Controlled clinical trials
      of monopreparations of CoQ10 administered orally to cancer patients were
      included. No language restrictions were imposed. Data were extracted
      independently by two authors according to predefined criteria. RESULTS: Six
      studies were included in the review, including three randomized clinical trials
      and three nonrandomized clinical trials. Patients in five of six studies received
      anthracyclines. The results suggested that CoQ10 provides some protection against
      cardiotoxicity or liver toxicity during cancer treatment. However, because of
      inadequate reporting and analysis, as well as questionable validity of outcome
      measures, the results are not conclusive. CONCLUSION: Suggestions that CoQ10
      might reduce the toxicity of cancer treatments have not been tested by rigorous
      trials. Further investigations are necessary to determine whether CoQ10 can
      improve the tolerability of cancer treatments.

PMID- 15514385
TI  - Fellow suffering.

PMID- 15514387
TI  - Iron supplement in cancer patients receiving erythropoietin.

PMID- 15514388
TI  - Myeloid growth factors should not be administered routinely after allogeneic
      hematopoietic stem-cell transplantation.

PMID- 15514390
TI  - Delayed-type hypersensitivity reaction with iscador M given in combination with
      cytotoxic chemotherapy.

PMID- 15514392
TI  - Diagnostic controversies in adult attention deficit hyperactivity disorder.
AB  - OBJECTIVE: While it is increasingly recognized that attention deficit
      hyperactivity disorder (ADHD) persists into adulthood, there is no consensus on
      diagnostic criteria for adult ADHD. In this article the authors describe and
      contrast competing approaches for diagnosis of adult ADHD used in clinical and
      research practice. METHOD: The authors review the Wender Utah criteria, DSM
      criteria, and laboratory assessment strategies for adult ADHD. Advantages and
      disadvantages of each approach are described, and recommendations are made as a
      basis for clinical assessment and future research. RESULTS: Both the Wender Utah
      criteria and DSM-based approaches identify significantly impaired ADHD adults
      with neurocognitive, biological, and treatment response patterns similar to
      pediatric ADHD patients. The Wender Utah criteria established the need for
      retrospective childhood diagnosis and recognize developmental differences in
      adult symptom expression. The Wender Utah criteria fail to identify patients with
      predominantly inattentive symptoms, exclude some patients with significant
      comorbid psychopathology, and diverge significantly from the DSM conception of
      ADHD. The DSM criteria have never been validated in adults, do not include
      developmentally appropriate symptoms and thresholds for adults, and fail to
      identify some significantly impaired adults who are likely to benefit from
      treatment. There are insufficient scientific data to justify use of laboratory
      assessment measures, including neuropsychological tests and brain imaging, in
      diagnosing adult ADHD. CONCLUSIONS: Adult ADHD remains a clinical diagnosis.
      Clinicians should be flexible in application of the current ADHD criteria to
      adults. Additional research is required to validate adult diagnostic criteria.

PMID- 15514393
TI  - Hippocampal volume and depression: a meta-analysis of MRI studies.
AB  - OBJECTIVE: Several studies have found reduced hippocampal volume in patients with
      unipolar depression, but discrepancies exist. The authors performed a systematic
      review and meta-analysis of volumetric studies of the hippocampus in patients
      with mood disorders. METHOD: Studies of hippocampal volume in unipolar and
      bipolar patients were identified. A meta-analysis of the 12 studies of unipolar
      depression fulfilling specific criteria was performed. The sample comprised 351
      patients and 279 healthy subjects. RESULTS: The studies were highly heterogeneous
      regarding age and gender distribution, age at onset of the disorder, average
      number of episodes, and responsiveness to treatment, but the pooled effect size
      of depression was significant in both hemispheres for the unipolar patients. The
      weighted average showed a reduction of hippocampal volume of 8% on the left side
      and 10% on the right side. The causes of the heterogeneity were analyzed, and a
      meta-regression showed that the total number of depressive episodes was
      significantly correlated to right but not left hippocampal volume reduction.
      CONCLUSIONS: Hippocampal volume is reduced in patients with unipolar depression,
      maybe as a consequence of repeated periods of major depressive disorder. Bipolar
      patients did not seem to show a reduction in hippocampal volume, but this has
      been much less investigated.

PMID- 15514394
TI  - Review of the validity and significance of cannabis withdrawal syndrome.
AB  - The authors review the literature examining the validity and significance of
      cannabis withdrawal syndrome. Findings from animal laboratory research are
      briefly reviewed, and human laboratory and clinical studies are surveyed in more
      detail. Converging evidence from basic laboratory and clinical studies indicates
      that a withdrawal syndrome reliably follows discontinuation of chronic heavy use
      of cannabis or tetrahydrocannabinol. Common symptoms are primarily emotional and
      behavioral, although appetite change, weight loss, and physical discomfort are
      also frequently reported. The onset and time course of these symptoms appear
      similar to those of other substance withdrawal syndromes. The magnitude and
      severity of these symptoms appear substantial, and these findings suggest that
      the syndrome has clinical importance. Diagnostic criteria for cannabis withdrawal
      syndrome are proposed.

PMID- 15514395
TI  - Prefrontal cortex, structural analysis: segmenting the prefrontal cortex.

PMID- 15514396
TI  - Autism in a 15-month-old child.

PMID- 15514397
TI  - Pliny Earle, M.D., 1809-1892.

PMID- 15514398
TI  - The effects of methylphenidate on neural systems of attention in attention
      deficit hyperactivity disorder.
AB  - OBJECTIVE: Recent studies have suggested that attention deficit hyperactivity
      disorder (ADHD) is associated with abnormalities in basal ganglia and prefrontal
      cortical functioning. However, these studies have primarily relied upon cognitive
      tasks that reflect impulse control rather than attentional mechanisms. METHOD:
      The authors used functional magnetic resonance imaging to investigate the neural
      correlates of selective and divided attention in a randomized, double-blind,
      placebo-controlled pharmacological challenge with methylphenidate in 15
      adolescents with ADHD (ages 14-17), eight adolescents with reading disorder (ages
      12-17), and four adolescents with both reading disorder and ADHD (ages 14-18) who
      were scanned during both a methylphenidate and a placebo session. Fourteen
      healthy comparison subjects (ages 12-20) who were not given methylphenidate
      served as the primary comparison group. RESULTS: During the divided attention
      task, unmedicated subjects with ADHD or reading disorder recruited the left
      ventral basal ganglia significantly less than the healthy comparison subjects.
      Methylphenidate led to an increase in activation in this region but had no effect
      on task performance. Subjects with ADHD also recruited the middle temporal gyrus
      significantly less than the comparison subjects, but methylphenidate did not have
      a direct effect on activation in this region. CONCLUSIONS: These results suggest
      that ADHD is associated with abnormal processing in attentional networks, with
      specific dysfunction in striatal circuitry. Methylphenidate may act to normalize
      activity within this network.

PMID- 15514399
TI  - Characteristics of depressed preschoolers with and without anhedonia: evidence
      for a melancholic depressive subtype in young children.
AB  - OBJECTIVE: This study investigated whether a melancholic subtype similar to that
      established in depressed adults can be identified in depressed preschool
      children. METHOD: A final group total of 156 preschool children between the ages
      of 3.0 and 5.6 years and their caregivers underwent a comprehensive psychiatric
      assessment that included a structured psychiatric interview modified for young
      children. The clinical characteristics of four study groups (N=156) were
      compared: depressed preschoolers with anhedonia, depressed preschoolers without
      anhedonia ("hedonic"), a psychiatric comparison group with DSM-IV attention
      deficit hyperactivity disorder and/or oppositional defiant disorder, and a
      healthy comparison group. RESULTS: Fifty-four depressed preschoolers were
      identified, and 57% of this depressed group was anhedonic, a symptom deemed to be
      highly developmentally and clinically significant when arising in the preschool
      period. The anhedonic depressed subgroup identified was characterized by greater
      depression severity, alterations in stress cortisol reactivity, increased family
      history of major depressive disorder, and increased frequency of psychomotor
      retardation as well as other melancholic symptoms, such as a lack of brightening
      in response to joyful events. CONCLUSIONS: The clinical characteristics of this
      depressed subgroup are consistent with those described in melancholic depressed
      adults and suggest that a melancholic depressed subtype can be manifest in
      children as young as age 3.

PMID- 15514400
TI  - Malnutrition at age 3 years and externalizing behavior problems at ages 8, 11,
      and 17 years.
AB  - OBJECTIVE: Poor nutrition is thought to predispose to externalizing behavior
      problems, but to date there appear to have been no prospective longitudinal
      studies testing this hypothesis. This study assessed whether 1) poor nutrition at
      age 3 years predisposes to antisocial behavior at ages 8, 11, and 17 years, 2)
      such relationships are independent of psychosocial adversity, and 3) IQ mediates
      the relationship between nutrition and externalizing behavior problems. METHOD:
      The participants were drawn from a birth cohort (N=1,795) in whom signs of
      malnutrition were assessed at age 3 years, cognitive measures were assessed at
      ages 3 and 11 years, and antisocial, aggressive, and hyperactive behavior was
      assessed at ages 8, 11, and 17 years. RESULTS: In relation to comparison subjects
      (N=1,206), the children with malnutrition signs at age 3 years (N=353) were more
      aggressive or hyperactive at age 8 years, had more externalizing problems at age
      11, and had greater conduct disorder and excessive motor activity at age 17. The
      results were independent of psychosocial adversity and were not moderated by
      gender. There was a dose-response relationship between degree of malnutrition and
      degree of externalizing behavior at ages 8 and 17. Low IQ mediated the link
      between malnutrition and externalizing behavior at ages 8 and 11. CONCLUSIONS:
      These results indicate that malnutrition predisposes to neurocognitive deficits,
      which in turn predispose to persistent externalizing behavior problems throughout
      childhood and adolescence. The findings suggest that reducing early malnutrition
      may help reduce later antisocial and aggressive behavior.

PMID- 15514401
TI  - Three-year predictive validity of DSM-IV attention deficit hyperactivity disorder
      in children diagnosed at 4-6 years of age.
AB  - OBJECTIVE: Predictive validity is a fundamental consideration in evaluating the
      DSM-IV diagnostic criteria for attention deficit hyperactivity disorder (ADHD),
      particularly for younger children. METHOD: The authors conducted four annual
      assessments of ADHD and functional impairment using multiple informants in 255
      probands and matched comparison children who were 4-6 years old in wave 1.
      RESULTS: Nearly all children who met full criteria for ADHD in wave 1 met full
      criteria for ADHD over the next 3 years and continued to display marked
      functional impairment relative to comparison children, even when intelligence, co
      occurring psychopathology, and demographic characteristics were controlled.
      CONCLUSIONS: These findings support the validity of the DSM-IV diagnosis of ADHD
      in younger children by demonstrating that the symptoms and associated impairment
      are likely to persist well into elementary school.

PMID- 15514402
TI  - Childhood videotaped social and neuromotor precursors of schizophrenia: a
      prospective investigation.
AB  - OBJECTIVE: The authors examined videotaped behaviors of children who developed
      schizophrenia as adults and of comparison subjects to disclose possible social
      and neuromotor deficits foreshadowing later development of schizophrenia. METHOD:
      In 1972, a sample of 265 11-13-year-old Danish children were filmed under
      standardized conditions while they were eating lunch. The examination was part of
      a larger study investigating early signs of schizophrenia spectrum disorders.
      Many of the subjects had a parent with schizophrenia, leaving them at high risk
      for developing a schizophrenia spectrum disorder. In 1991, adult psychiatric
      outcome data were obtained for 91.3% (N=242). This study systematically analyzed
      the videotapes to determine whether the children who developed schizophrenia as
      adults evidenced greater social and/or neuromotor deficits than children who did
      not develop a psychiatric disorder and children who developed other psychiatric
      disorders. RESULTS: The findings from this study suggest that the brief
      videotaped footage of children eating lunch was able to discriminate between the
      individuals who later developed schizophrenia and those who did not.
      Specifically, the preschizophrenia children evidenced differences on measures of
      sociability and general neuromotor functioning (among boys) from the children who
      developed other psychiatric disorders and the children who did not develop a
      psychiatric disorder. CONCLUSIONS: Social and neuromotor deficits specific to
      children who develop schizophrenia in adulthood provide further support for a
      neurodevelopmental hypothesis of schizophrenia.

PMID- 15514403
TI  - Altered interhemispheric connectivity in individuals with Tourette's disorder.
AB  - OBJECTIVE: The corpus callosum is the major commissure connecting the cerebral
      hemispheres. Prior evidence suggests involvement of the corpus callosum in the
      pathophysiology of Tourette's disorder. The authors assessed corpus callosum size
      and anatomical connectivity across the cerebral hemispheres in persons with
      Tourette's disorder. METHOD: The size of the corpus callosum was determined on
      the true midsagittal slices of reformatted, high-resolution magnetic resonance
      imaging scans and compared across groups in a cross-sectional case-control study
      of 158 subjects with Tourette's disorder and 121 healthy comparison subjects,
      ages 5-65 years. RESULTS: In the context of increasing midsagittal corpus
      callosum area from childhood to age 30 years, children with Tourette's disorder
      had smaller overall corpus callosum size, whereas adults with Tourette's disorder
      on average had larger corpus callosum size, yielding a prominent interaction of
      diagnosis with age. Corpus callosum size correlated positively with tic severity.
      Corpus callosum size also correlated inversely with dorsolateral prefrontal and
      orbitofrontal cortical volumes in both the subjects with Tourette's disorder and
      the comparison subjects, but the magnitudes of the correlations were
      significantly greater in the group with Tourette's disorder. The effects of
      medication and comorbid illnesses had no appreciable influence on the findings.
      CONCLUSIONS: Given prior evidence for the role of prefrontal hypertrophy in the
      regulation of tic symptoms, the current findings suggest that neural plasticity
      may contribute to smaller corpus callosum size in persons with Tourette's
      disorder, which thereby limits neuronal trafficking across the cerebral
      hemispheres and reduces input to cortical inhibitory interneurons within the
      prefrontal cortices. Reduced inhibitory input may in turn enhance prefrontal
      excitation, thus helping to control tics and possibly contributing to the
      cortical hyperexcitatibility reported previously in patients with Tourette's
      disorder.

PMID- 15514404
TI  - Hippocampus and amygdala volumes in parents of children with autistic disorder.
AB  - OBJECTIVE: Structural and functional abnormalities in the medial temporal lobe,
      particularly the hippocampus and amygdala, have been described in people with
      autism. The authors hypothesized that parents of children with a diagnosis of
      autistic disorder would show similar changes in these structures. METHOD:
      Magnetic resonance imaging scans were performed in 17 biological parents of
      children with a diagnosis of DSM-IV autistic disorder. The scans were compared
      with scans from 15 adults with autistic disorder and 17 age-matched comparison
      subjects with no personal or familial history of autism. The volumes of the
      hippocampus, amygdala, and total brain were measured in all participants.
      RESULTS: The volume of the left hippocampus was larger in both the parents of
      children with autistic disorder and the adults with autistic disorder, relative
      to the comparison subjects. The hippocampus was significantly larger in the
      adults with autistic disorder than in the parents of children with autistic
      disorder. The left amygdala was smaller in the adults with autistic disorder,
      relative to the other two groups. No differences in total brain volume were
      observed between the three groups. CONCLUSIONS: The finding of larger hippocampal
      volume in autism is suggestive of abnormal early neurodevelopmental processes but
      is partly consistent with only one prior study and contradicts the findings of
      several others. The finding of larger hippocampal volume for the parental group
      suggests a potential genetic basis for hippocampal abnormalities in autism.

PMID- 15514405
TI  - Research design features and patient characteristics associated with the outcome
      of antidepressant clinical trials.
AB  - OBJECTIVE: The authors examined which, if any, research design features and
      patient characteristics would significantly differ between successful and
      unsuccessful antidepressant trials. METHOD: Clinical trial data were reviewed for
      nine antidepressants approved by the Food and Drug Administration between 1985
      and 2000. From the antidepressant research programs on these medications, 52
      clinical trials were included in the study. The authors evaluated trial design
      features, patient characteristics, and difference in response between placebo and
      antidepressant. RESULTS: Nine trial design features and patient characteristics
      were present in the research programs for all nine of the antidepressants. The
      severity of depressive symptoms before patient randomization, the dosing schedule
      (flexible versus fixed), the number of treatment arms, and the percentage of
      female patients were significantly associated with the difference in response to
      antidepressant and placebo. The duration of the antidepressant trial, number of
      patients per treatment arm, number of sites, and mean age of the patients were
      similar in successful trials (with a greater antidepressant-placebo difference)
      and less successful trials (with a smaller antidepressant-placebo difference).
      CONCLUSIONS: These findings may help in the design of future antidepressant
      trials.

PMID- 15514406
TI  - Antidepressant pharmacotherapy in the treatment of depression in the very old: a
      randomized, placebo-controlled trial.
AB  - OBJECTIVE: This study determined the efficacy of antidepressant medication for
      the treatment of depression in the "old-old." METHOD: This randomized 8-week
      medication trial compared citalopram, 10-40 mg/day, to placebo in the treatment
      of patients 75 and older with unipolar depression. RESULTS: A total of 174
      patients who were 58% women with a mean age of 79.6 years (SD=4.4) and a mean
      baseline Hamilton Depression Rating Scale score of 24.3 (SD=4.1) were randomly
      assigned to treatment at 15 sites. There was a main effect for site but not for
      treatment condition. The remission rate, defined as a final Hamilton depression
      scale score <10, was 35% for the citalopram and 33% for the placebo groups.
      However, patients with severe depression (baseline Hamilton depression scale
      score >24) tended to have a higher remission rate with medication than with
      placebo (35% versus 19%). CONCLUSIONS: In the oldest group of community-dwelling
      patients to be studied to date, medication was not more effective than placebo
      for the treatment of depression. However, given the considerable psychosocial
      support received by all patients, the placebo condition represents more than the
      ingestion of an inactive pill. Across sites, there was considerable range in
      response to medication, 18% to 82%, and to placebo, 16% to 80%.

PMID- 15514407
TI  - Comparison of two-phase treatment with imipramine or fluvoxamine, both followed
      by lithium addition, in inpatients with major depressive disorder.
AB  - OBJECTIVE: This study was designed to compare the efficacy of two two-phase
      pharmacological treatment strategies for inpatients with DSM-IV major depressive
      disorder. METHOD: During phase I, patients participated in a double-blind study
      of the effects of imipramine versus fluvoxamine, with final evaluation of
      response 4 weeks after patients attained the target plasma level. In phase II,
      for patients without treatment response or with partial response in phase I,
      lithium was added to imipramine or fluvoxamine. Final evaluation of response was
      made 3 weeks after the patients attained the target plasma level of lithium (0.6
      1.0 mmol/liter). RESULTS: One hundred thirty-eight patients were enrolled in the
      study. At the end of phase I, remission, defined as a final Hamilton Depression
      Rating Scale score < or =7, was achieved by 16 (23%) of 70 imipramine-treated
      patients and 10 (15%) of 68 fluvoxamine-treated patients. At the end of phase II,
      41 (59%) of 70 imipramine-treated patients versus 27 (40%) of 68 fluvoxamine
      treated patients qualified for remission, a significant difference in favor of
      the imipramine strategy. Only a small minority of both groups received
      concomitant medication. In both phase I and phase II, the discontinuation rate
      was low (5% and 10%, respectively). CONCLUSIONS: Imipramine with subsequent
      lithium addition is superior to a similar strategy with fluvoxamine for treatment
      of severely depressed inpatients. Both strategies were well tolerated.

PMID- 15514408
TI  - Beta-arrestin-1 levels: reduced in leukocytes of patients with depression and
      elevated by antidepressants in rat brain.
AB  - OBJECTIVE: Beta-arrestins play a pivotal role in G protein-coupled receptor
      desensitization. beta-Arrestins interfere in G protein receptor interaction, thus
      leading to desensitization of G protein-mediated receptor signaling. G protein
      receptor signaling and its desensitization were previously implicated in the
      pathophysiology of mood disorders and in the mechanism of action of
      antidepressant and mood-stabilizing treatments. The present study aims at
      quantitatively evaluating beta-arrestin-1 levels in leukocytes of patients with
      major depression and the effect of antidepressants on beta-arrestin-1 levels in
      rat brain. METHOD: Beta-arrestin-1 measurements were carried out in cortical,
      hippocampal, and striatal brain regions of rats chronically intragastrically
      treated with either imipramine, desipramine, or fluvoxamine. Similar measurements
      were conducted in mononuclear leukocytes of 36 untreated patients with major
      depression and 32 healthy volunteer subjects. Beta-arrestin-1 levels were
      evaluated through immunoblot analyses using monoclonal antibodies to beta
      arrestin-1. RESULTS: Beta-arrestin-1 levels were significantly elevated by all
      three antidepressants in rat cortex and hippocampus, while in the striatum no
      alterations could be detected. This process became significant within 10 days and
      took 2-3 weeks to reach maximal increase. Mononuclear leukocytes of patients with
      depression showed significantly reduced immunoreactive quantities of beta
      arrestin-1. The reduction in beta-arrestin-1 levels was significantly correlated
      with the severity of depressive symptoms. CONCLUSIONS: The findings in the rat
      study suggest beta-arrestin-1 elevation as a biochemical mechanism for
      antidepressant-induced receptor down-regulation. The findings in human subjects
      support the implication of beta-arrestin-1 in the pathophysiology of mood
      disorders. Beta-arrestin-1 measurements in patients with depression may
      potentially serve as a biochemical marker for depression.

PMID- 15514409
TI  - Clinical outcome of ECT in patients with major depression and comorbid borderline
      personality disorder.
AB  - OBJECTIVE: Previous research suggests that the comorbidity of major depression
      with a personality disorder, especially borderline personality disorder, is
      associated with a poorer response to ECT. The authors compared the acute outcome
      of ECT in depressed patients with borderline personality disorder, with
      personality disorders other than borderline personality disorder, and with no
      personality disorder. METHOD: The study subjects were 139 patients with a primary
      diagnosis of unipolar major depression and scores of at least 20 on the 24-item
      Hamilton Depression Rating Scale. Patients were treated with suprathreshold right
      unilateral or bilateral ECT in a standardized manner and were assessed with the
      Hamilton depression scale within 3 days and 4-8 days after completing ECT.
      RESULTS: Compared to patients with personality disorders other than borderline
      personality disorder (N=42) and those with no personality disorder (N=77),
      patients with borderline personality disorder (N=20) had less symptomatic
      improvement assessed up to 8 days after ECT. Patients with personality disorders
      other than borderline personality disorder responded as well to ECT as those with
      no personality disorder. Borderline personality disorder patients were more
      likely to be female and to have medication-resistant depression than the patients
      in the two comparison groups; they were also younger. However, none of these
      differences accounted for the borderline personality disorder patients' poorer
      response to ECT. CONCLUSIONS: Patients with borderline personality disorder have
      a poorer acute response to ECT, but explanations for this finding remain elusive.

PMID- 15514410
TI  - A longitudinal study of hippocampal volume, cortisol levels, and cognition in
      older depressed subjects.
AB  - OBJECTIVE: This study determined whether cognitive impairments and structural
      brain changes in older depressed subjects, especially in the hippocampus, are
      related to hypercortisolemia. METHOD: Sixty-one depressed subjects over age 60
      who met DSM-IV criteria for major depression and 40 healthy comparison subjects
      underwent structural magnetic resonance imaging, neuropsychological testing,
      apolipoprotein E (APOE) genotyping, and salivary cortisol assessment (over 3
      days) with follow-up 6 months later. Hippocampal volume was measured by manual
      segmentation that was blind to diagnosis. Average area under the curve for
      salivary cortisol over the 3 days was calculated. Cognitive function was assessed
      by using a combined memory z score. RESULTS: Depressed subjects showed multiple
      impairments in attention, working memory, visual memory, verbal memory, new
      learning, and executive function in relation to comparison subjects. They had
      hypercortisolemia (53% increase in area under the curve) and a reduction in right
      hippocampal volume (6% decrease). Hippocampal volume reduction was not associated
      with increased cortisol levels but was significantly correlated with continuing
      memory deficits at 6 months. Persisting "mild cognitive impairment" was seen in
      20 (41%) of 49 subjects at 6 months and was associated with reduced hippocampal
      volume but not severity of depression, cortisol levels, or APOE genotype.
      CONCLUSIONS: Older depressed subjects have persisting cognitive impairments
      associated with hippocampal volume reduction, but the results do not support
      cortisol-mediated hippocampal neurotoxicity as the major etiological mechanism.
      Neuropathological studies are required to investigate the basis for hippocampal
      changes, while follow-up will determine whether hippocampal atrophy is a risk
      factor for cognitive decline.

PMID- 15514411
TI  - Localizing gray matter deficits in late-onset depression using computational
      cortical pattern matching methods.
AB  - OBJECTIVE: The authors used magnetic resonance imaging and an image analysis
      technique known as cortical pattern matching to map cortical gray matter deficits
      in elderly depressed patients with an illness onset after age 60 (late-onset
      depression). METHOD: Seventeen patients with late-onset depression (11 women and
      six men; mean age=75.24, SD=8.52) and 17 group-matched comparison subjects (11
      women and six men; mean age=73.88, SD=7.61) were included. Detailed spatial
      analyses of gray matter were conducted across the entire cortex by measuring
      local proportions of gray matter at thousands of homologous cortical surface
      locations in each subject, and these patterns were matched across subjects by
      using elastic transformations to align sulcal topography. To visualize regional
      changes, statistical differences were mapped at each cortical surface location in
      three dimensions. RESULTS: The late-onset depression group exhibited significant
      gray matter deficits in the right lateral temporal cortex and the right parietal
      cortex, where decreases were most pronounced in sensorimotor regions. The
      statistical maps also showed gray matter deficits in the same regions of the left
      hemisphere that approached significance after permutation testing. No significant
      group differences were detected in frontal cortices or any other anatomical
      region. CONCLUSIONS: Regionally specific decreases of gray matter occur in late
      onset depression, supporting the hypothesis that this subset of elderly patients
      with major depression presents with certain unique neuroanatomical abnormalities
      that may differ from patients with an earlier onset of illness.

PMID- 15514412
TI  - Extended nortriptyline and psychological treatment for cigarette smoking.
AB  - OBJECTIVE: Accepted treatments for cigarette smoking rarely achieve abstinence
      rates of >35% at 1 year. Low rates may reflect failure to provide extended and
      multifocal treatment for this complex and chronic addiction. Using a chronic
      disease model of smoking, the authors undertook a study to determine the effects
      of long-term antidepressant and psychological treatment. METHOD: One hundred
      sixty smokers of > or =10 cigarettes/day were randomly assigned to one of four
      treatment conditions in a two-by-two (nortriptyline versus placebo by brief
      versus extended treatment) design. All subjects received 8 weeks of a transdermal
      nicotine patch, five group counseling sessions, and active or placebo treatment.
      Interventions for subjects in brief treatment ended at this point. Subjects in
      extended treatment continued taking drug or placebo to week 52 and received an
      additional 9 monthly counseling sessions, with checkup telephone calls midway
      through each session. Subjects were assessed at baseline and weeks 12, 24, 36,
      and 52. The principal outcome variables were repeated abstinence at each
      assessment after the first over a 1-year period and a point prevalence of 7 days
      of abstinence. RESULTS: At week 52, point-prevalence abstinence rates with
      missing subjects imputed as smokers were 30% for placebo brief treatment, 42% for
      placebo extended treatment, 18% for active brief treatment, and 50% for active
      extended treatment. With missing subjects omitted, these rates were 32%, 57%,
      21%, and 56%, respectively. CONCLUSIONS: Comprehensive extended treatments that
      combine drug and psychological interventions can produce consistent abstinence
      rates that are substantially higher than those in the literature.

PMID- 15514413
TI  - Axis I comorbidity in patients with borderline personality disorder: 6-year
      follow-up and prediction of time to remission.
AB  - OBJECTIVE: The purpose of this study was to assess the prevalence of axis I
      disorders among patients with borderline personality disorder over 6 years of
      prospective follow-up. METHOD: A semistructured interview of demonstrated
      reliability was used to assess presence or absence of comorbid axis I disorders
      in 290 patients who met Revised Diagnostic Interview for Borderlines criteria and
      DSM-III-R criteria for borderline personality disorder and 72 patients who did
      not meet these criteria but did meet DSM-III-R criteria for another axis II
      disorder. Over 94% of surviving patients were reinterviewed about their axis I
      disorders at 2-year, 4-year, and 6-year follow-up periods. RESULTS: Although the
      patients with borderline personality disorder experienced declining rates of many
      axis I disorders over time, the rates of these disorders remained high,
      particularly the rates of mood and anxiety disorders. Patients whose borderline
      personality disorder remitted over time experienced substantial decline in all
      comorbid disorders assessed, but those whose borderline personality disorder did
      not remit over time reported stable rates of comorbid disorders. When the absence
      of comorbid axis I disorders was used to predict time to remission, the absence
      of substance use disorders was a far stronger predictor of remission from
      borderline personality disorder than was the absence of posttraumatic stress
      disorder, mood disorders, other anxiety disorders, or eating disorders,
      respectively. CONCLUSIONS: The results of this study suggest that axis I
      disorders are less common over time in patients with initially severe borderline
      personality disorder, particularly for patients whose borderline personality
      disorder remits over time. The findings also suggest that substance use disorders
      are most closely associated with the failure to achieve remission from borderline
      personality disorder.

PMID- 15514414
TI  - A pilot study of D-cycloserine in subjects with autistic disorder.
AB  - OBJECTIVE: The authors assessed the effects of D-cycloserine on the core symptom
      of social impairment in subjects with autism. METHOD: Following a 2-week, single
      blind placebo lead-in phase, drug-free subjects with autistic disorder were
      administered three different doses of D-cycloserine during each of three 2-week
      periods. Measures used for subject ratings included the Clinical Global
      Impression (CGI) scale and Aberrant Behavior Checklist. RESULTS: Significant
      improvement was found on the CGI and social withdrawal subscale of the Aberrant
      Behavior Checklist. d-Cycloserine was well tolerated at most of the doses used in
      this study. CONCLUSIONS: In this pilot study, D-cycloserine treatment resulted in
      significant improvement in social withdrawal. Further controlled studies of D
      cycloserine in autism appear warranted.

PMID- 15514415
TI  - Perception of complex sounds in autism: abnormal auditory cortical processing in
      children.
AB  - OBJECTIVE: The authors have previously described less activation of left speech
      related temporal areas in adults with autism when listening to speech-like sounds
      than in normal adults. Here, they investigated whether this abnormal cortical
      processing was also present in children with primary autism. METHOD: Regional
      cerebral blood flow was measured with positron emission tomography after
      premedication in 11 autistic children and six nonautistic mentally retarded
      children during rest and while they were listening to speech-like sounds.
      RESULTS: As with autistic adults, direct comparison between the two groups
      revealed significantly less activation in the autistic group localized in left
      speech-related areas. CONCLUSIONS: For the first time to their knowledge, an
      activation study was performed in children with autism and has confirmed previous
      results obtained in adults. The abnormal cortical auditory processing observed in
      both children and adults with autism could be involved in inadequate behavioral
      responses to sounds and in language impairments characteristic of autism.

PMID- 15514416
TI  - Serum lipid levels in patients with dissociative disorder.
AB  - OBJECTIVE: There may be an association between a low serum cholesterol level and
      dissociative disorders. METHOD: The subjects of the study were 16 patients with
      dissociative disorder and 16 normal comparison subjects (two men and 14 women in
      each group). Total cholesterol, triglyceride, high-density lipoprotein, low
      density lipoprotein, and very low density lipoprotein levels were compared.
      RESULTS: Patients with dissociative disorders had lower serum triglyceride, total
      cholesterol, low-density lipoprotein, and very low density lipoprotein levels
      than normal comparison subjects. CONCLUSIONS: Low serum lipid concentrations may
      be related to a high incidence of self-injurious behaviors and borderline
      features in patients with dissociative disorders.

PMID- 15514417
TI  - Cholesterol metabolism and suicidality in Smith-Lemli-Opitz syndrome carriers.
AB  - OBJECTIVE: The authors examined the relationship between cholesterol metabolism
      and suicidality in carriers of Smith-Lemli-Opitz syndrome and their families.
      This population has a partial deficiency in 7-dehydrocholesterol reductase
      (DHCR7), the enzyme that catalyzes the last step in cholesterol biosynthesis.
      METHOD: Suicidal behavior, depression, misuse of alcohol and drugs, and family
      history of psychopathology, including attempted or completed suicide, were
      assessed by structured interview in 51 carriers of Smith-Lemli-Opitz syndrome and
      54 matched comparison subjects. RESULTS: There were significantly more suicide
      attempters and completers among the biological relatives of Smith-Lemli-Opitz
      syndrome carriers than comparison subjects, but family history of psychopathology
      did not significantly differ between the groups. More suicide attempts were
      reported among Smith-Lemli-Opitz syndrome carriers than among the comparison
      subjects. CONCLUSIONS: These results, based on a unique study design, provide
      additional evidence supporting the relationship between cholesterol metabolism
      and suicidal behavior.

PMID- 15514418
TI  - Functional neuroimaging evidence for hyperarousal in insomnia.
AB  - OBJECTIVE: The authors investigated the neurobiological basis of poor sleep and
      daytime fatigue in insomnia. METHOD: [(18)F]Fluorodeoxyglucose positron emission
      tomography was used to assess regional cerebral glucose metabolism of seven
      patients with insomnia and 20 healthy subjects. RESULTS: Compared with healthy
      subjects, patients with insomnia showed greater global cerebral glucose
      metabolism during sleep and while awake, a smaller decline in relative metabolism
      from waking to sleep states in wake-promoting regions, and reduced relative
      metabolism in the prefrontal cortex while awake. CONCLUSIONS: Subjectively
      disturbed sleep in patients with insomnia is associated with greater brain
      metabolism. The inability to fall asleep may be related to a failure of arousal
      mechanisms to decline in activity from waking to sleep states. Further, daytime
      fatigue may reflect decreased activity in the prefrontal cortex resulting from
      inefficient sleep.

PMID- 15514419
TI  - Psychiatric morbidity among homicide offenders: a Swedish population study.
AB  - OBJECTIVE: The authors examined psychiatric diagnoses of all individuals
      convicted of homicide and attempted homicide in Sweden from 1988 to 2001
      (N=2,005). METHOD: High-quality national crime and hospital registers were linked
      to investigate standardized psychiatric diagnoses of homicide offenders. RESULTS:
      The presence or absence of psychiatric diagnoses was ascertained for 1,625 (81%)
      of the homicide offenders; 1,464 (90%) of these offenders had a psychiatric
      diagnosis. Twenty percent (N=409) of all 2,005 offenders had a psychotic illness,
      and 54% (N=589) of a subgroup of 1,091 offenders with information on secondary
      diagnoses had a personality disorder as a principal or secondary diagnosis. Only
      10% of the offenders for whom psychiatric diagnostic information was available
      had no diagnosis. CONCLUSIONS: Using a comprehensive method for identifying
      psychiatric illness in homicide offenders, the authors found higher rates of
      psychiatric morbidity than previous studies. Their findings underline the
      importance of psychiatric assessment in homicide offenders and suggest that
      treatment might have a preventive role.

PMID- 15514420
TI  - Carbamazepine and rebound mania.

PMID- 15514421
TI  - Riluzole augmentation for treatment-resistant depression.

PMID- 15514422
TI  - Catatonia in juvenile corrections.

PMID- 15514423
TI  - Vardenafil reversal of female anorgasmia.

PMID- 15514424
TI  - Overlap between alexithymia and Asperger's syndrome.

PMID- 15514425
TI  - Anorexia nervosa and gastrointestinal tumors.

PMID- 15514427
TI  - Terrorism and psychiatric disorders.

PMID- 15514428
TI  - Estradiol effects on the postmenopausal brain.

PMID- 15514429
TI  - Depression treatment during pregnancy.

PMID- 15514431
TI  - The hippocampus in schizophrenia.

PMID- 15514430
TI  - Pregnancy and antidepressant counseling.

PMID- 15514432
TI  - Functionalizing diagnostics.

PMID- 15514433
TI  - A mood stabilizer with risperidone or haloperidol for mania.

PMID- 15514434
TI  - Traffic accidents and Friday the 13th.

PMID- 15514435
TI  - A mood stabilizer with risperidone or haloperidol for mania.

PMID- 15514436
TI  - Comment on adult baby syndrome.

PMID- 15514437
TI  - Psychiatrists as expert witnesses.

PMID- 15514438
TI  - Determinants of sensitivity and specificity in spotted DNA microarrays with
      unmodified oligonucleotides.
AB  - DNA microarrays with unmodified oligonucleotides are a cost-effective alternative
      to cDNA microarrays. This study examined how purity, length, homology and GC
      content of the oligonucleotide probes influence the sensitivity and specificity
      of the method using cyanobacterial genes. Oligonucleotide purification by high
      pressure liquid chromatography was omitted without significant reduction in
      hybridization sensitivity. For two of three genes tested, a reduction in
      oligonucleotide length did not reduce hybridization sensitivity, and maximum
      sensitivity was achieved with probes that were 45 nt long. Oligonucleotide probes
      with <or=71% contiguous sequence identity to non-target DNA cross-hybridized with
      the sequences at a rate of < 8%. Cross-hybridization decreased as the GC content
      decreased from 65% to 55% or 35%. These results support the following criteria
      for selecting unmodified oligonucleotide probes that generate sensitive and
      specific microarrays: length of 45 nt, <or=71% identity to non-target sequences,
      and <or=55% GC content. In most of the bacterial species tested, oligonucleotide
      probes meeting these criteria were successfully designed for more than 95% of
      genes.

PMID- 15514439
TI  - Forchlorfenuron, a phenylurea cytokinin, disturbs septin organization in
      Saccharomyces cerevisiae.
AB  - Septins, which are involved in cytokinesis, have been identified in a variety of
      fungi and animal cells. For analysis of the function of septin, drugs targeting
      septin would be useful; however, no such drugs have been available hitherto. By
      serendipity, we found that forchlorfenuron (FCF, N-(2-chloro-4-pyridyl)-N
      phenylurea, 4PU300), a synthetic plant cytokinin, disturbed cytokinesis in
      Saccharomyces cerevisiae. Upon administration of FCF, septin structures at the
      bud neck became deformed and filament-like septin appeared outside of the neck.
      Under these conditions, the localization of actin was normal and Gin4, which is
      localized at the bud neck in a septin-dependent manner, was found to remain at
      the location of apparently normal septin at the bud neck, whereas it was not co
      localized to the deformed septin at the bud neck or to septin seen outside the
      bud neck. FCF administration immediately induced production of sporadic septin
      structures outside the bud neck, and these structures disappeared promptly upon
      removal of the drug. Taken together, these findings indicate that FCF maybe a
      promising drug for investigating the structure and function of septin.

PMID- 15514440
TI  - A defect in atToc159 of Arabidopsis thaliana causes severe defects in leaf
      development.
AB  - Plastid protein import 2 (ppi2), a mutant of Arabidopsis thaliana, lacks a
      homologue of a component of the translocon at the outer envelope membrane of
      chloroplasts (Toc), designated Toc159 of the pea. Toc159 is thought to be
      essential for the import of photosynthetic proteins into chloroplasts. In order
      to investigate the effect of protein import on the plant development, we examined
      the morphologies of the developing leaves and the shoot apical meristems (SAM) in
      the ppi2 plants. Our histological analysis revealed that the development of
      leaves is severely affected in ppi2, while the structure of SAM is normal.
      Abnormalities in leaves became obvious in the later stages of leaf development,
      resulting in the generation of mature leaves with fewer mesophyll cells and more
      intercellular spaces as compared with the wild type. Palisade and spongy tissues
      of the mature leaves were indistinguishable in ppi2. Replication of chloroplast
      DNA was also suggested to be impaired in ppi2. Our results suggest that protein
      import into chloroplasts is important for the normal development of leaves.

PMID- 15514441
TI  - Identification and molecular characterization of novel anther-specific genes in
      Oryza sativa L. by using cDNA microarray.
AB  - The complicated genetic pathway regulates the developmental programs of male
      reproductive organ, anther tissues. To understand these molecular mechanisms, we
      performed cDNA microarray analyses and in situ hybridization to monitor gene
      expression patterns during anther development in rice. Microarray analysis of
      4,304 cDNA clones revealed that the hybridization signal of 396 cDNA clones (271
      non-redundant groups) increased more than six-fold in every stage of the anthers
      compared with that of leaves. Cluster analysis with the expression data showed
      that 259 cDNA clones (156 non redundant groups) were specifically or
      predominantly expressed in anther tissues and were regulated by developmental
      stage-specific manners in the anther tissues. These co-regulated genes would be
      important for development of functional anther tissues. Furthermore, we selected
      several clones for RNA in situ hybridization analysis. From these analyses, we
      found several novel genes that show temporal and spatial expression patterns
      during anther development in addition to anther-specific genes reported so far.
      These results indicate that the genes identified in this experiment are
      controlled by different programs and are specialized in their developmental and
      cell types.

PMID- 15514442
TI  - Construction of a full-length cDNA library from young spikelets of hexaploid
      wheat and its characterization by large-scale sequencing of expressed sequence
      tags.
AB  - The polyploid nature of wheat is a key characteristic of the plant. Full-length
      complementary DNAs (cDNAs) provide essential information that can be used to
      annotate the genes and provide a functional analysis of these genes and their
      products. We constructed a full-length cDNA library derived from young spikelets
      of common wheat, and obtained 24056 expressed sequence tags (ESTs) from both ends
      of the cDNA clones. These ESTs were grouped into 3605 contigs using the phrap
      method, representing expressed loci from each of the three genomes. Using BLAST,
      3605 contigs were grouped into 1902 gene clusters, showing that loci of the three
      genomes are not always expressed. A homology search of these gene clusters
      against a wheat EST database (15964 gene clusters) and a rice full-length cDNA
      database (21447 gene clusters) revealed that a quarter of the wheat full-length
      cDNAs were novel. A protein database of Arabidopsis was used to examine the
      functional classification of these gene clusters. The GC-content in the 5 -UTR
      region of wheat cDNAs was compared to that of rice. Forty-three genes (3.5% of
      wheat cDNAs homologous to those of rice) possessed distinct GC-content in the 5 
      UTR region, suggesting different breeding behaviors of wheat and rice.

PMID- 15514443
TI  - Colonization of America by Drosophila subobscura: association between Odh gene
      haplotypes, lethal genes and chromosomal arrangements.
AB  - The colonization of America by Drosophila subobscura has been a unique exper
      iment in nature that has allowed us to explore the effects of evolution on a
      continental scale. To analyze this evolutionary event, nucleotide sequences of
      the Odh (Octanol dehydrogenase) gene were obtained for 43 lethal chromosomal
      lines from colonizing populations of North America and 5 from South America, in
      addition to 5 chromosomal lines from Europe with different viabilities and 2 from
      laboratory marker stocks. Since 10 different Odh haplotypes were found in
      America, the minimum number of colonizers would be 5 (or 3 mated females). Only
      one Odh haplotype was found in American O(5) inversions confirming that only one
      copy of this inversion was included among the sample of colonizers. The same Odh
      haplotypes were detected in association with the same chromosomal arrangements
      and with identical lethal genes in both North and South America indicating that
      exactly the same chromosome types reached both hemispheres. These observations
      indicate that the two continental colonizations are not independent. They are
      derived from the same colonization event. The population from which the
      colonization started should contain the O(5) inversion, a non-negligible
      frequency of the O(3+4+7) arrangement and all other arrangements found in
      America. So far the only populations that fulfill all these requirements are
      those from Greece, indicating that these populations can be considered good
      candidates as a starting point for an in depth analysis of the origin of the
      American colonization by D. subobscura.

PMID- 15514444
TI  - A PCR-based marker for targeting small rye segments in wheat background.
AB  - We attempted to develop a PCR-based marker that detects various segments of rye
      chromosome incorporated into wheat. We designed three sets of PCR primers based
      on the nucleotide sequence data of a rye repetitive sequence previously reported.
      One of the primer sets amplified a clear ca. 1.4 kb fragment in a rye cultivar
      but not in any form of wheat, diploid, tetraploid or hexaploid. We used this
      critical primer set for PCR of various wild species and cultivars of rye, an
      array of wheat plants carrying different rye chromosomes or small segments from
      different regions of rye chromosome 1R, and plants carrying parts of the rye B
      chromosome. The PCR amplified the 1.4 kb fragment in all the plant materials
      examined. We believe this PCR primer set will be useful as a universal PCR-based
      marker for the introgression of rye chromosome segments in the wheat genome.

PMID- 15514445
TI  - Construction of a bacterial artificial chromosome library from the inshore
      hagfish, Eptatretus burgeri: A resource for the analysis of the agnathan genome.
AB  - The jawless fish occupy an important phylogenetic position for understanding the
      evolution of body plans, the origin of adaptive immunity and genome evolution in
      chordates. We describe here the construction of a large-insert bacterial
      artificial chromosome (BAC) library from the inshore hagfish, Eptatretus burgeri.
      The BAC library contains 93,978 clones with an average insert size of 100 kb and
      is estimated to represent threefold genome-equivalent coverage. The library was
      organized in three-dimensional pools to facilitate screening by PCR. We have
      screened this library by PCR and isolated several BAC clones; the average number
      of positive clones was compatible with the estimated genome coverage of the
      library. This BAC library, constructed for the first time from the jawless fish,
      should serve as a useful resource for the scientific community.

PMID- 15514446
TI  - Thin is better!: ultrathin cryosection immunocytochemistry.
AB  - In immunofluorescence microscopy (IFM), the repression of out of focus
      fluorescence signal is crucial in order to obtain high-resolution images. One
      option to acquire high vertical resolution (z-axis resolution) is to produce
      optical sections with a confocal microscope. The z-axis resolution usually
      obtained with confocal microscopy of biological samples is about 500 nm. Another
      option is to produce very thin sections with a cryo-ultramicrotome (physical
      sections). The ultrathin cryosections we employ are about 100 nm in thickness:
      thus all of the fluorescence must come from within this 100 nm thickness. The use
      of ultrathin cryosections permits the acquisition of extremely high-quality
      images and minimizes the possibility for false localization in IFM (Fig. 1).
      Ultrathin cryosections can be applied to immunoelectron microscopy (IEM) as well
      as IFM (Fig. 2). We show new methods of ultrathin cryosection
      immunocytochemistry(1-3). Human full-term placentas were fixed with 4%
      paraformaldehyde, solidified with 10% gelatin, infiltrated with 2.3 M sucrose,
      and then frozen in liquid nitrogen. Ultrathin cryosections were cut with a cryo
      ultramicrotome and then transferred to glass cover slips for IFM or to nickel
      grids for IEM. Cryosections were incubated with mouse anti-p230, a trans-Golgi
      network marker, and subsequently incubated with Alexa 488-labeled goat anti-mouse
      IgG or with goat anti-mouse 5-nm colloidal gold particles. For visualization and
      preservation of ultrastructure of cryosections at the electron microscopic level,
      the sections on grids were postfixed with ferrocyanide-reduced osmium and then
      stained with uranyl acetate and lead citrate in polyvinyl alcohol(1). Ultrathin
      cryosection immunocytochemistry should be an important technique for functional
      genomics research, especially for the analysis of the in situ expression of
      target molecules(2,3).

PMID- 15514447
TI  - Diagnosis and treatment of recurrent miscarriage associated with immunologic
      disorders: Is paternal lymphocyte immunization a relic of the past?
AB  - Miscarriage is the most common complication of human pregnancy. Although the
      causes of recurrent miscarriage (RM) are various, immunologic aberrations between
      mother and fetus might be one of the causes of miscarriage. Immune responses fall
      into two categories: autoimmune and alloimmune. Currently, no appropriate
      diagnostic method has been established to identify alloimmune causes. We observed
      that NK cell activity in women with RM was higher than that in women without a
      history of miscarriage. Functional or quantitative analysis of NK cells could be
      used to identify alloimmune causes. Paternal lymphocyte immunization has been the
      most widely used treatment for alloimmune-mediated miscarriages. However, the
      latest Cochrane review by Scott reached the current conclusion that lymphocyte
      immunization therapy provided no significant beneficial effect over placebo in
      preventing further miscarriage. Approximately 70% of Japanese university
      hospitals are still performing paternal lymphocyte immunization. Is paternal
      lymphocyte immunization a relic of the past? Randomized controlled trials based
      on adequate patient selection in Japan should provide an answer to this question.

PMID- 15514448
TI  - Cross-cultural validation of the Japanese Functional Assessment of Cancer Therapy
      Anemia (FACT-An).
AB  - BACKGROUND: The Functional Assessment of Cancer Therapy-Anemia (FACT-An)
      questionnaire, which consists of a core questionnaire named the General Measure
      of the Functional Assessment of Cancer Therapy (FACT-G) and the Anemia additional
      concerns subscale, was developed in an English-speaking culture. The validation
      of the Japanese FACT-G was reported previously (Fumimoto et al., 2001), and, in
      this report, a cross-cultural validation for the subscale was performed. METHODS:
      The Japanese version was developed through an iterative forward-backward
      translation sequence used throughout the Functional Assessment of Chronic Illness
      Therapy (FACIT) Multilingual Translation Project. In evaluating psychometric
      performance, its construct validity was investigated by exploratory factor
      analyses, and confirmed by Cronbach's alpha coefficient. RESULTS: The FACT-An was
      given to 180 patients with lung cancer. Using the 20 items of the Anemia
      subscale, a factor analysis extracted four factors of fatigue, chest condition,
      activities and headache. When analyzed as two extracted factors, fatigue, chest
      condition and headache were combined to be a major factor, although the minor
      factor of activities still remained. Thirteen of the 20 items construct the
      Fatigue additional concerns subscale. Cronbach's alpha coefficients for the
      Fatigue subscale (0.93) and the Anemia subscale (0.88) confirmed that, although
      these subscales had items that focus on different aspects of anemia or fatigue,
      each subscale was unidimensional. Clinical validity was indicated by moderate
      values of Spearman's correlation coefficients between Eastern Cooperative
      Oncology Group performance status rating (ECOG PSR) and the Anemia subscale (
      0.50) or the Fatigue subscale (-0.48). CONCLUSION: Both the Fatigue subscale and
      the Anemia subscale are valid in Japan, indicating that FACT-An is an instrument
      that is applicable across cultures and particularly with a Japanese cancer
      population.

PMID- 15514449
TI  - Significance of preserving the posterior branch of the great auricular nerve in
      parotidectomy.
AB  - OBJECTIVE: Sensory disturbance due to excision of the great auricular nerve in
      patients who have undergone parotidectomy sometimes causes discomfort to the
      patients. In order to reduce the postoperative discomfort of the pinna, we tried
      to preserve the posterior branch of the great auricular nerve. METHODS: Forty
      patients with parotid tumor were included in this study. Twenty-one of these
      patients had pleomorphic adenoma, 16 had adenolymphoma and 3 had a low grade
      malignant tumor. Sensations of the pinna and the quality of life (QOL) after
      parotidectomy were evaluated using a 0-100 Visual Analogue Scale (VAS) assessed
      at 2 weeks, 1 month, 2 months, 3 months and 6 months after parotidectomy.
      RESULTS: The posterior branch of the great auricular nerve was preserved in 26
      out of 40 patients (65%). No difference was observed in the incidence of
      complications except sensory disturbance of the pinna with this surgical
      procedure as compared to the surgical technique where the great auricular nerve
      was excised. The VAS score for the sensation was significantly higher in the
      group of patients whose great auricular nerve was preserved at 2 months (35.0+/
      20.8 vs. 18.5+/-9.2), 3 months (64.4+/-18.3 vs. 26.4+/-13.8) and 6 months (66.9+/
      16.2 vs. 26.6+/-11.4) after parotidectomy. The VAS score for the QOL was also
      significantly higher in the group of patients whose great auricular nerve was
      preserved at 2 months (50.3+/-21.8 vs. 35.1+/-14.5), 3 months (69.5+/-27.5 vs.
      45.9+/-22.6) as well as 6 months (71.9+/-24.1 vs. 45.7+/-19.1) after
      parotidectomy. CONCLUSION: Preservation of the posterior branch of the great
      auricular nerve during parotidectomy is valuable in order to reduce the
      postoperative sensory disturbance of the pinna that follows conventional surgery.
      It further helps to improve the QOL of these patients after parotidectomy.

PMID- 15514450
TI  - Prenatal diagnosis of congenital heart disease: clinical experience and analysis.
AB  - Over a five-year period, we reviewed 19 fetuses who were prenatally diagnosed
      with congenital heart disease, including hemodynamically significant arrhythmias.
      Five of them had fetal tachyarrhythmias, and 14 had structural heart disease. The
      outcomes were: six intrauterine deaths, five neonatal deaths, and three infant
      surgeries. Six of the fetuses had chromosomal abnormalities, four had
      extracardiac anomalies, and two had hydrops fetalis. Of the 96 neonates with
      congenital heart disease found during the study period, the overall detection
      rate was 20%; 16% of the neonates with structural cardiac defects and 83% of the
      neonates with arrhythmias. Some of the complex cardiac defects with normal fetal
      four-chamber view were difficult to detect prenatally. During the course of the
      pregnancy, 37% of the fetuses with prenatally diagnosed congenital heart disease
      were found to have intrauterine growth retardation, and 26% were found to have an
      abnormal amniotic fluid volume. In view of our findings, a comprehensive
      screening system should be more frequently considered in order to improve both
      detection rate and perinatal management.

PMID- 15514451
TI  - Video-assisted thoracic surgery for pulmonary aspergilloma in patients with
      anorexia nervosa.
AB  - We report a case of pulmonary aspergilloma in a 27-year-old woman with anorexia
      nervosa who underwent a video-assisted thoracic surgery (VATS) lobectomy. On
      admission, she had lost 38% of her original weight but the laboratory data were
      normal. She had refused treatment for anorexia nervosa for nine years ago and may
      have been predisposed to opportunistic conditions. The aspergilloma was developed
      in a simple bulla formed in the course of healing of a lung abscess and a VATS
      lobectomy was safely and cosmetically performed. Wedge resection was difficult
      due to the size of the lesion. The residual lobes expanded very well and the
      postoperative course was uneventful. VATS is considered to be an efficient method
      in the treatment of pulmonary aspergilloma in patients with better lung function
      and localized pulmonary disease.

PMID- 15514452
TI  - Simple closure of a perforated duodenal diverticulum: "a case report".
AB  - Spontaneous perforation of a duodenal diverticulum is a rare but serious
      complication with significant mortality rates. Just over 100 cases have been
      reported in the world literature. One case of perforated duodenal diverticulum
      treated by simple closure is reported. An elderly female was admitted to our
      hospital with an acute abdomen. Computed tomography of the abdomen showed
      retroperitoneal air around the duodenum and right kidney. Laparotomy with a
      Kocher maneuver disclosed a perforated diverticulum in the second portion of the
      duodenum. Although diverticulectomy is the most common treatment, simple closure
      of the perforated duodenal diverticulum with drainage was performed to avoid
      injury to the distal common bile duct and ampulla of Vater, which were close to
      the diverticulum. The patient has fully recovered and has been asymptomatic with
      no signs of recurrence for 25 months.

PMID- 15514453
TI  - Post-cataract surgery endophthalmitis treated with core vitrectomy: a case
      report.
AB  - Postoperative endophthalmitis is one of the most serious complications after
      cataract surgery though its frequency may be low. We report a case with post
      cataract extraction bacterial endophthalmitis treated favorably by core
      vitrectomy through pars plana with anterior vitrectomy cutter (A-vit). The
      patient, a 72-year-old woman, presented with blurred vision 7 days after
      phacoemulsification and aspiration (PEA) and intraocular lens (IOL) implantation.
      Her initial visual acuity was counting fingers. As hypopyon and corneal edema
      progressed in a few hours, we decided to perform vitectomy. Firstly, we performed
      IOL explantation and anterior vitrectomy through the corneal stab incision with A
      vit attached to the phaco machine. The inflammation, however, appeared to be
      severe. Secondly we performed core vitrectomy with the same cutter as we used in
      the first operation through pars plana as well as intravitreal injection of
      vancomycin on the following day. The inflammation was gradually subsided and her
      corrected visual acuity was recovered to 30/20 at 7 months after the vitrectomy.
      The results is suggest that for cataract surgeons in the facilities that are not
      equipped with 3-port vitrectomy machine, post-cataract extraction bacterial
      endophthalmitis of the emergency stage can be successfully treated by core
      vitrectomy through pars plana as well as intravitreal injection of antibiotics
      with neither vitreous shaving at the vitreous base nor artificial posterior
      vitreous detachment.

PMID- 15514454
TI  - Analysis of antimicrobial drug resistance of Staphylococcus aureus strains by
      WHONET 5: microbiology laboratory database software.
AB  - OBJECTIVES: To analyze our hospital laboratory microbiological data by using
      WHONET 5-Microbiology laboratory database software-, and to acquire information
      about antimicrobial resistance of Staphylococcus aureus strains among every ward.
      MATERIALS AND METHODS: The database of Staphylococcus aureus strains had been
      brought to our hospital microbiology laboratory from every ward in our hospital
      from September 2001 till December 2002. Analysis was performed under the
      condition as one isolate per one patient. Starting of "resistance profile"
      analysis in WHONET 5 and analyzing the microbiological laboratory testing reports
      for every ward. We chose Oxacillin, Levofloxacin, Erythromycin and Gentamicin as
      the antimicrobials that need to be investigated for resistance. We evaluated the
      monthly transition of resistance ratios with regard to the specific wards that
      have the moving lines of inpatients in order to verify the hypothesis that
      resistant strains may be carried from ward to ward along the moving lines of
      inpatients. RESULTS: The data of 2,113 Staphylococcus aureus strains were
      accumulated and analyzed. Overall Oxacillin resistance ratio in our hospital was
      65.7%. The ward of the smallest Oxacillin resistance ratio was
      Pediatrics/Ophthalmology ward. The ratios of Oxacillin resistant were varied as
      from 67.9% to 96.7% regardless the categories of wards such as internal medicine
      or surgery. Multi-resistant MRSA strains were overwhelmingly dominant in the
      wards of surgery. The ratios of the Gentamicin sensitive strains that were
      resistant to Oxacillin were high over the every ward. The moving lines of
      inpatients existed between ICU/CCU ward and three rear wards. Two rear wards
      whose Oxacillin resistance changes were reflected to those of ICU/CCU, but one
      rear ward was not. CONCLUSION: Variation of resistant degree among wards were
      very obvious and large. We could survey the wards where patient-to-patient
      transmission of resistant organisms might occur along the moving lines of
      inpatients. WHONET 5 will be recognized as an analysis and surveillance tool for
      every infection control team to survey the suspicious wards.

PMID- 15514455
TI  - Early access to patients with life-threatening cardiovascular disease by an air
      ambulance service.
AB  - The purpose of this study was to determine whether use of an air ambulance
      service using a helicopter with a critical care physician and nurse on board
      (doctor helicopter service; DHS) could shorten the prehospital delay. We
      evaluated the initial treatment time and the transport time in 30 patients
      transported by DHS and 30 patients transported by ground ambulance service (GAS).
      The initial treatment time was significantly shorter in the DHS group (11.3+/-5.4
      min) than in the GAS group (29.5+/-15.3 min). But the transport time in the DHS
      group (26.1+/-8.6 min) was not different from that in the GAS group. The
      difference in the initial treatment time was remarkable for patients transported
      from distant areas (12.7+/-5.6 min for DHS, and 42.1+/-13.8 min for GAS) and DHS
      shortened the initial treatment time by 30 min compared with GAS. The transport
      time was shorter for DHS (30.5+/-9.9 min) than for GAS (42.1+/-13.8 min) for
      patients transported from distant areas, but it was not significantly different
      for patients transported from nearby areas (22.3+/-5.0 min for DHS, and 18.4+/
      2.4 min for GAS). In conclusion, DHS is important in the management of life
      threatening cardiovascular diseases, and has a significant impact when GAS cannot
      transport a patient to the hospital within 20 min.

PMID- 15514456
TI  - Regulation mechanism of selective atresia in porcine follicles: regulation of
      granulosa cell apoptosis during atresia.
AB  - More than 99% of follicles undergo a degenerative process known as "atresia", in
      mammalian ovaries, and only a few follicles ovulate during ovarian follicular
      development. We have investigated the molecular mechanism of selective follicular
      atresia in mammalian ovaries, and have reported that follicular selection
      dominantly depends on granulosa cell apoptosis. However, we have little knowledge
      of the molecular mechanisms that control apoptotic cell death in granulosa cells
      during follicle selection. To date, at least five cell death ligand-receptor
      systems [tumor necrosis factor (TNF)alpha and receptors, Fas (also called APO
      1/CD95) ligand and receptors, TNF-related apoptosis-inducing ligand (TRAIL; also
      called APO-2) and receptors, APO-3 ligand and receptors, and PFG-5 ligand and
      receptors] have been reported in granulosa cells of porcine ovaries. Some cell
      death ligand-receptor systems have "decoy" receptors, which act as inhibitors of
      cell death ligand-induced apoptosis in granulosa cells. Moreover, we showed that
      the porcine granulosa cell is a type II apoptotic cell, which has the
      mitochondrion-dependent apoptosis-signaling pathway. Briefly, the cell death
      receptor-mediated apoptosis signaling pathway in granulosa cells has been
      suggested to be as follows. (1) A cell death ligand binds to the extracellular
      domain of a cell death receptor, which contains an intracellular death domain
      (DD). (2) The intracellular DD of the cell death receptor interacts with the DD
      of the adaptor protein (Fas-associated death domain: FADD) through a homophilic
      DD interaction. (3) FADD activates an initiator caspase (procaspase-8; also
      called FLICE), which is a bipartite molecule, containing an N-terminal death
      effector domain (DED) and a C-terminal DD. (4) Procaspase-8 begins auto
      proteolytic cleavage and activation. (5) The auto-activated caspase-8 cleaves Bid
      protein. (6) The truncated Bid releases cytochrome c from mitochondrion. (7)
      Cytochrome c and ATP-dependent oligimerization of apoptotic protease-activating
      factor-1 (Apaf-1) allows recruitment of procaspase-9 into the apoptosome complex.
      Activation of procaspase-9 is mediated by means of a conformational change. (8)
      The activated caspase-9 cleaves downstream effector caspases (caspase-3). (9)
      Finally, apoptosis is induced. Recently, we found two intracellular inhibitor
      proteins [cellular FLICE-like inhibitory protein short form (cFLIPS) and long
      form (cFLIPL)], which were strongly expressed in granulosa cells, and they may
      act as anti-apoptotic/survival factors. Further in vivo and in vitro studies will
      elucidate the largely unknown molecular mechanisms, e. g. which cell death ligand
      receptor system is the dominant factor controlling the granulosa cell apoptosis
      of selective follicular atresia in mammalian ovaries. If we could elucidate the
      molecular mechanism of granulosa cell apoptosis (follicular selection), we could
      accurately diagnose the healthy ovulating follicles and precisely evaluate the
      oocyte quality. We hope that the mechanism will be clarified and lead to an
      integrated understanding of the regulation mechanism.

PMID- 15514457
TI  - Cathepsin gene expression in mouse placenta during the latter half of pregnancy.
AB  - Gene expressions and their interaction are complex and have not been definitely
      clarified in the placenta. To identify interactions of gene products previously
      not studied, we applied cDNA subtraction analyses to the placenta between days 12
      and 16, days 12 and 14, days 14 and 16 of pregnancy. Among subtracted cDNAs
      cathepsin M, Q and R in PECs were specifically identified on days 14 and 16
      pregnancy. All of these gene expressions exhibited a similar pattern to the mPL
      II gene expression determined by northern blot and RT-PCR analyses. By means of
      in situ hybridization, these mRNAs were localized in the basal and labyrinth
      zones of the placenta on day 16 of pregnancy. Double staining studies of
      cathepsin Q or cathepsin R mRNA by in situ hybridization followed by
      immunohistochemical staining of mPL-II in the same section revealed that signals
      for cathepsin Q and cathepsin R mRNAs were colocalized in mPL-II immunopositive
      trophoblast cells in the basal and labyrinth zones of the placenta on day 16 of
      pregnancy. Possible association of cathepsins with mPL-II may play important
      roles in placental functions during the latter half of pregnancy in mice.

PMID- 15514458
TI  - Comparative studies on lipid analysis and ultrastructure in porcine and southern
      minke whale (Balaenoptera bonaerensis) oocytes.
AB  - The present study was conducted to clarify the difference in the color of the
      cytoplasm in immature follicular oocytes from prepubertal and adult minke whales.
      The four lipid contents (triglyceride, total cholesterol, phospholipids and non
      esterified fatty acids) in vitrified immature oocytes from prepubertal and adult
      minke whales, and also in fresh and vitrified immature porcine oocytes, were
      measured. The lipid contents in vitrified-warmed minke whale oocytes were
      similarly high compared with those in vitrified-warmed porcine oocytes. In
      particular, the total cholesterol and phospholipid contents in the vitrified
      immature oocytes from prepubertal and adult minke whales were significantly
      (P<0.05) higher than those from prepubertal pigs. Furthermore, the distribution
      of lipid droplets in fresh and vitrified immature oocytes was observed in
      transmission electron microscopy. Lipid droplets in the prepubertal minke whale
      oocytes were distributed throughout the cytoplasm. In contrast, adult minke
      whales had larger lipid droplets which were distributed mainly in the central
      portion of the cytoplasm. The lipid droplets of immature oocytes from prepubertal
      pigs were larger than those in minke whale oocytes. These results indicated that
      the difference in the distribution of the cytoplasmic lipid droplets may result
      in the difference in the color tone of both prepubertal and adult whale oocyte
      cytoplasm.

PMID- 15514459
TI  - Factors required during preculture of rat oocytes soon after sperm penetration
      for promoting their further development in a chemically defined medium.
AB  - Blastocyst formation in a chemically defined medium (mR1ECM) of rat oocytes soon
      after sperm penetration is less frequent than in those undergoing male pronuclear
      formation. This inhibition is released by preculturing the oocytes for a few
      hours in modified Krebs-Ringer bicarbonate solution (mKRB). The present study
      examined the effects of phosphate (Pi), bovine serum albumin (BSA) and osmolarity
      during preculture of sperm penetrated rat oocytes on their development to
      blastocysts in mR1ECM in vitro. These are the major factors that differ between
      mR1ECM and mKRB. When oocytes collected at 0730-0800 h on the day following
      mating and freed from cumulus cells were precultured for 5 h in mKRB or Pi-free
      mKRB and then cultured for 127 h in mR1ECM, about 73-74% of oocytes developed to
      blastocysts. In both media, replacement of BSA with polyvinylalcohol (PVA) or
      osmolarity of 246 mOsM reduced blastocyst formation compared with media
      containing BSA or with osmolarity of 304 mOsM; blastocyst formation was greatly
      inhibited when oocytes were precultured in media with PVA and osmolarity of 246
      mOsM. On the other hand, when precultured in mR1ECM or mR1ECM with osmolarity of
      304 mOsM or BSA instead of PVA, fewer oocytes developed to blastocysts than those
      precultured in Pi-free mKRB and mR1ECM with osmolarity of 304 mOsM and BSA. These
      results indicate that both BSA and osmolarity, but not Pi, are essential factors
      during preculture of rat oocytes soon after sperm penetration for promoting their
      further development to blastocysts in a chemically defined medium.

PMID- 15514460
TI  - Bovine oocytes grown in serum-free medium acquire fertilization competence.
AB  - We previously found that bovine oocytes 90-99 microm in diameter in early antral
      follicles grew to nearly their final size in serum-free medium, with some of the
      oocytes acquiring the nuclear competence to reach the second metaphase. In the
      present study, we examined the competence of the fertilization and pre
      implantational development of the oocytes grown in serum-free medium. Bovine
      early antral follicles, 0.4-0.7 mm in diameter, were collected mechanically using
      fine forceps, embedded in collagen gels, and cultured in serum-free medium for 16
      days. Grown oocytes which were enclosed by granulosa cells and did not show
      disintegrated ooplasm were recovered as normal oocytes, were transferred to the
      maturation medium, and then inseminated with spermatozoa. Ten to 12 h after
      insemination, 28% (41/145) of the oocytes were penetrated by spermatozoa. Of the
      penetrated oocytes, 18 (12%) formed a female and a male pronuclei, and 10 (7%)
      had a female pronucleus and an enlarged sperm head. Among the abnormally
      penetrated oocytes (13/41), 10 were penetrated by multiple spermatozoa and 3 were
      penetrated by a spermatozoon at the first metaphase stage. Of the 106 inseminated
      oocytes grown under serum-free conditions, 8 oocytes had cleaved and developed to
      the 2-cell stage 48 h after insemination, and 3-4-cell embryos and 5-8-cell
      embryos were observed after 72-96 h. However, no embryo developed to the
      blastocyst stage within 8 days. These results indicate that bovine oocytes grown
      in serum-free medium can be fertilized, but acquire insufficient embryonic
      development competence under the employed culture conditions.

PMID- 15514461
TI  - Porcine (Sus scrofa) cellular FLICE-like inhibitory protein (cFLIP): molecular
      cloning and comparison with the human and murine cFLIP.
AB  - To reveal the molecular regulation mechanism of selective follicular atresia in
      porcine ovaries, we isolated the porcine cDNA encoding cellular FLICE-like
      inhibitory protein (cFLIP), which inhibits death receptor-mediated apoptosis
      signal transduction. Two alternative splicing isoforms of cFLIP, porcine cellular
      FLIP-short form (pcFLIPS, 642 bp and 214-aa) and -long form (pcFLIPL, 1446 bp and
      482-aa), were identified from a cDNA library prepared from follicular granulosa
      cells of pig ovaries. pcFLIPS and pcFLIPL indicated high identities with human
      and murine cFLIP, and both of them contain two tandem specific amino acid regions
      (death effector domain: DED) in their N-terminal, suggesting that pcFLIPS and
      pcFLIPL inhibit the death receptor-mediated apoptosis signal by binding to other
      pro-apoptotic factors mediated by DED. pcFLIPS contains a short C-terminal
      region, while pcFLIPL has a caspase-like domain in the C-terminal region. The
      reverse transcription-polymerase chain reaction analysis revealed that both
      pcFLIPS and pcFLIPL mRNAs were highly expressed in granulosa cells of healthy
      follicles, suggesting that these cFLIPs play important roles in the regulation
      mechanism of apoptosis in ovarian follicular granulosa cells. The present data
      will contribute to understanding of the physiological roles of cFLIPs in the
      apoptosis regulation in porcine tissues.

PMID- 15514462
TI  - Prominent expression of spinocerebellar ataxia type-1 (SCA1) gene encoding ataxin
      1 in LH-producing cells, LbetaT2.
AB  - The LH-producing cell line, LbetaT2, and non LH-producing cell line, alphaT3-1
      cells, established from a pituitary tumor, were employed for cDNA subtraction
      cloning to identify genes with expression unique to LH producing cells. Several
      cDNAs that code for known as well as for many unidentified clones were
      discovered. Most clones were the spinocerebellar ataxia type-1 (SCA1) gene
      encoding ataxin-1, the abnormality of which causes neurodegeneration and loss of
      cerebellar Purkinje cells. We examined whether the expression of SCA1 gene in
      LbetaT2 cells is related to hormone production. We also compared the expression
      of SCA1 with that in various other pituitary tumor derived cell lines, and
      confirmed the prominent expression of SCA1 in LbetaT2 cells. The effect of
      gonadal factor(s) for SCA1 gene expression was examined. The expression level in
      female rats was low and did not change during the estrus cycle, but increased
      significantly after ovariectomy and did not return to the normal level under low
      and high doses of estrogen. In the male pituitary SCA1 gene expression increased
      markedly after castration and was not decreased by estrogen or testosterone. The
      Ontogeny of SCA1 gene expression was investigated in porcine fetal and postnatal
      pituitaries and revealed biphasic and sexually dimorphic expression. Transient
      expression of SCA1 gene was observed at fetal day 50 and 65 in males and day 40
      in females, followed by a decline and increased expression before birth in both
      genders. Thus the expression of SCA1 gene is prominent in LH-producing cells and
      is not under direct control of gonadal factor(s) in both genders. In addition to
      the variable expression of SCA1 gene during the fetus period, the present results
      provide a novel aspect to the understanding of Boucher-Neuhauser syndrome (Ataxia
      Hypogonadism Choroidal Dystrophy).

PMID- 15514463
TI  - Expression of Prnp mRNA (prion protein gene) in mouse spermatogenic cells.
AB  - The Prnp (prion protein) gene, which encodes a soluble protein anchored to the
      cell surface by glycosylphosphatidylinositol (GPI), might be involved in cell-to
      cell interaction. The expression of Prnp is strongly observed not only in the
      brain, but also in non-neuronal tissues. In order to examine the Prnp expression
      sites in mouse testes, we carried out Northern blot and in situ hybridization
      analyses. By Northern blot analysis, two kinds of Prnp transcripts (major band of
      2.2 kb, and minor band of 1.1 kb) were detected in testes. The 2.2-kb transcript
      was observed in testes throughout the postnatal development, whereas the 1.1-kb
      transcript was observed in testes from 2 to 70 weeks old. In situ hybridization
      analysis showed that the positive signals for Prnp mRNAs were predominantly
      observed in spermatogenic cells, but not in somatic cells such as Sertoli cells,
      Leydig cells and peritubular myoid cells. The signals were observed moderately in
      spermatogonia, and strongly in spermatocytes and round spermatids, but not in
      elongate spermatids and spermatozoa. These results suggest that Prnp may be
      involved in germ cell differentiation during mammalian spermatogenesis.

PMID- 15514464
TI  - Synthesis, processing, and subcellular localization of mouse ADAM3 during
      spermatogenesis and epididymal sperm transport.
AB  - To elucidate synthesis, processing, and subcellular localization of mouse ADAM3
      (cyritestin) during spermatogenesis and epididymal sperm transport, we carried
      out immunoblotting and immunohistochemical analysis of testicular germ cells, and
      epididymal and vas deferens sperm, using affinity-purified anti-ADAM3 antibody.
      ADAM3 was initially synthesized as a 110-kDa precursor in round spermatids, and
      the precursor was then processed into a 42-kDa mature protein during the sperm
      transport into and/or once in the epididymis. The mature ADAM3 was localized on
      the anterior part of capacitated sperm heads and was rapidly removed from the
      head region during the calcium ionophore A23187-induced acrosome reaction. These
      results demonstrate that the mature form of ADAM3 is involved in the binding of
      sperm to the egg zona pellucida, not in the membrane fusion between sperm and
      egg.

PMID- 15514465
TI  - In vitro culture of mouse preantral follicles using membrane inserts and
      developmental competence of in vitro ovulated oocytes.
AB  - To develop a reliable follicle culture system, mouse preantral follicles 150-200
      microm in diameter were cultured individually for 5 or 6 days in membrane inserts
      or in droplets, and then induced to ovulate with hCG (Experiment 1). The nuclear
      maturation and developmental competence of the oocytes that ovulated from the
      follicles cultured in inserts were determined (Experiment 2). There was no
      significant difference between the two culture systems in the survival rate (83
      and 77%). However, follicles cultured in inserts showed a higher ovulation rate
      (63%) than those cultured in droplets (39%, P<0.05). About 80% of the oocytes
      that ovulated from the follicles cultured in inserts were at the metaphase II
      stage. After in vitro fertilization, 75 and 48% of in vitro ovulated oocytes
      cleaved and developed into blastocysts, respectively. These results demonstrate
      that the insert culture system is superior to the droplet culture system in terms
      of follicular growth and ovulation, and can be used to investigate the growth and
      ovulation of follicles in vitro.

PMID- 15514467
TI  - Cryopreservation of bovine somatic cell nuclear-transferred blastocysts: effect
      of developmental stage.
AB  - The effect of developmental stage on the survival of bovine somatic cell nuclear
      transferred blastocysts after freezing and thawing was evaluated. We also
      investigated how freezing affects nuclear-transferred (NT) embryos and in vitro
      fertilized (IVF) bovine embryos. Advanced-stage bovine NT blastocysts survived
      freezing better than early-stage NT blastocysts (86 vs 14%). The trend was
      similar with IVF embryos (87 vs 30%). At the stages tested, there was no
      significant difference in the survivability of NT and IVF embryos from advanced
      (86 vs 87%) or early-stage blastocysts (14 vs 30%). The average survival rate did
      not differ between NT and IVF bovine embryos (50 vs 51%). The higher survival
      rate of advanced-stage blastocysts compared to early-stage blastocysts in NT and
      IVF bovine embryos might be due to their higher cell number. In NT (128 +/- 25 vs
      53 +/- 20) and IVF (128 +/- 29 vs 75 +/- 22) groups, advanced-stage blastocysts
      contained a significantly higher total cell number than early-stage blastocysts.
      There was no difference in total cell number between advanced-stage NT and IVF
      blastocysts (128 +/- 25 vs 128 +/- 29), however, early-stage NT and IVF
      blastocysts (53 +/- 20 vs 75 +/- 22) differed significantly.

PMID- 15514466
TI  - Effect of replacement of pyruvate/lactate in culture medium with glucose on
      preimplantation development of porcine embryos in vitro.
AB  - The effect of glucose supplementation at different times in in vitro culture on
      the developmental competence of in vitro produced (IVP) porcine embryos was
      examined. In Experiment 1, when IVP embryos were cultured in modified NCSU-37
      supplemented with pyruvate and lactate (IVC-pyr/lac) for 0 h, 24 h, 48 h, 72 h,
      96 h, or 118 h and subsequently in modified NCSU-37 supplemented with glucose
      (IVC-glu) until Day 6 (Day 0=day of in vitro fertilization), the rates of
      blastocyst formation were significantly higher in embryos cultured in IVC-pyr/lac
      for 24 or 48 h (24.4% and 23.0%, respectively) than in embryos cultured in IVC
      pyr/lac for the whole culture period (14.5%). However, there were no significant
      differences between embryos obtained after the energy source replacement and
      embryos cultured in IVC-glu for the whole culture period on the rates (15.2%
      24.4%, and 16.8% respectively). Replacement of pyruvate/lactate with glucose at
      58 h of culture in Experiment 2 significantly enhanced the rate (31.3%) compared
      to those after replacement at 48 h, 53 h and 63 h of culture (20.6%, 20.8%, and
      21.1%, respectively). In conclusion, replacement of pyruvate/lactate with glucose
      as the energy substrate was optimal at 58 h of culture for the development of
      porcine embryos to the blastocyst stage.

PMID- 15514468
TI  - Evaluation of RNA interference in developing porcine granulosa cells using
      fluorescence reporter genes.
AB  - Gene silencing using small interfering RNA (siRNA) may be useful for functional
      analyses of unidentified genes expressed during cell differentiation. The present
      study was performed to evaluate RNA interference (RNAi) in porcine granulosa
      cells stimulated with bovine FSH, by using two fluorescence reporter genes: a
      plasmid encoding green fluorescent protein (GFP) and a plasmid encoding red
      fluorescent protein (RFP). The siRNA targeting GFP mRNA sequence (GFP-siRNA) with
      both plasmids was introduced into cultured cells by lipofection. GFP- and RFP
      expressing cells were observed under fluorescence microscopy and analyzed by flow
      cytometry. Strong fluorescence was observed after introduction of both plasmids
      into cells. The intensity of green fluorescence generated by GFP was greatly
      suppressed by introduction of GFP-siRNA, showing an approximate 70% decrease in
      the ratio of green to red fluorescence. Consequently, we concluded that gene
      silencing by siRNA can be used to analyze the functions of genes of interest
      during differentiation of porcine granulosa cells.

PMID- 15514469
TI  - GnRH as a cell proliferation regulator: mechanism of action and evolutionary
      implications.
AB  - Gonadotropin-releasing hormone (GnRH) is well known as the central regulator of
      the reproductive system through its stimulation of gonadotropin release from the
      pituitary. Studies on GnRH have demonstrated that GnRH has both stimulatory and
      inhibitory effects on cell proliferation depending on the cell type; however, the
      mechanisms of these effects remain to be elucidated. Against this background we
      used four human cell lines, TSU-Pr1, Jurkat, HHUA and DU145, and newly found that
      GnRH increased or decreased the colony-formation depending on the cell line.
      Moreover, we demonstrated that the stimulatory and inhibitory effects of GnRH
      exhibit distinct ligand selectivities. In order to investigate the molecular
      basis of these phenomena, analyses of the expression of human GnRH receptors were
      performed and, moreover, the effects of GnRH were analyzed under conditions in
      which human GnRH receptors were knocked down by the technique of RNA
      interference. Consequently, it was found that human type II GnRH receptor, which
      had been suspected of being nonfunctional because of alterations in its sequence,
      is involved in the effects of GnRH on cell proliferation. In this article, the
      influence of the autocrine activities of the cells is also reviewed, focusing on
      the characteristics of substances secreted from the four cell lines. Based on
      recent studies of GnRH and its receptors and our up-to-date findings, the
      evolutionary implications of GnRH action are discussed.

PMID- 15514470
TI  - The XX-XY sex-determination system in Oryzias luzonensis and O. mekongensis
      revealed by the sex ratio of the progeny of sex-reversed fish.
AB  - The sex-determining gene in Oryzias latipes and O. curvinotus has been proved to
      be DMY. Although O. curvinotus has the DMY gene on the Y chromosome which is
      homologous to the Y chromosome of O. latipes, the sex-determining mechanism of
      other Oryzias fishes has not been identified. In order to uncover the sex
      determining mechanism of O. luzonensis and O. mekongensis, which are most closely
      related species to O. latipes and O. curvinotus, we analyzed the sex ratio of the
      progeny of sex-reversed fish. We were able to obtain sex-reversed males by the
      administration of methyltestosterone, and found that these yielded all-female
      offspring in both species. These results indicate that O. luzonensis and O.
      mekongensis have the XX-XY sex-determination system.

PMID- 15514471
TI  - Elemental characterization of Daphnia resting eggs by X-ray analytical
      microscopy.
AB  - Resting eggs of Daphnia, a key crustacean zooplankton of freshwater food chains,
      can remain viable for more than a century. These eggs are able to withstand
      freezing and drying, and can survive the harsh environment of a predator's
      digestive system. Until recently little was known about the chemical composition,
      microanatomy, and physical properties of the resting eggs. The current study
      utilized a physical technique, the X-ray analytical microscope, to identify and
      localize component elements of the Daphnia resting egg. The analysis demonstrated
      that phosphorus, sulfur, potassium, and calcium were detected as elemental
      components of the resting egg, and detection intensities of the four elements
      differed according to the position of the eggs. Phosphorus and calcium were
      mostly detected in regions of the eggshell that surrounded the two embryos. In
      addition, sulfur was distributed throughout the eggshell whereas potassium was
      localized to the areas that corresponded to where the embryos were encased.
      Through the use of X-ray analytical microscopy, the current study identifies
      elemental characteristics in relationship to the structure of the Daphnia resting
      eggs.

PMID- 15514472
TI  - Behavior of pigment cells closely correlates the manner of gastrulation in sea
      urchin embryos.
AB  - To know whether behavior of pigment cells correlates the process of gastrulation
      or not, gastrulating embryos of several species of regular echinoids
      (Anthocidaris crassispina, Mespilia globulus and Toxopneustes pileolus) and
      irregular echinoids (Clypeaster japonicus and Astriclypeus manni) were examined.
      In M. globulus and A. crassispina, the archenteron elongated stepwise like in
      well-known sea urchins. In the embryos of both species, fluorescent pigment cells
      left the archenteron tip and migrated into the blastocoel during gastrulation. In
      T. pileolus, C. japonicus and A. manni, on the other hand, the archenteron
      elongated at a constant rate throughout gastrulation. In these species, no
      pigment cell was observed at the archenteron tip during invagination processes;
      pigment cells began to migrate in the ectoderm from the vegetal pole side toward
      the apical plate without entering the blastocoel. These results clearly indicate
      that the behavior of pigment cells closely correlated the manner of gastrulation.
      Further, it was examined whether the archenteron cells are rearranged during
      invagination, by comparing the number of cells observed on cross sections of the
      archenteron at the early and late gastrula stages. The rearrangement was not
      conspicuous in A. crassispina and M. globulus, in which archenteron elongated
      stepwise. In contrast, the archenteron cells were remarkably rearranged in C.
      japonicus, alothough the archenteron elongated continuously. Thus, neither the
      behavior of pigment cells nor the manner of gastrulation matches the current
      taxonomic classification of echinoids.

PMID- 15514473
TI  - Ovarian development and hemolymph vitellogenin levels in laboratory-maintained
      protandric shrimp, Pandalus hypsinotus: measurement by a newly developed time
      resolved fluoroimmunoassay (TR-FIA).
AB  - Most pandalid shrimps exhibit protandric hermaphroditism, and detailed
      information on ovarian development of pandalid species is important for a better
      understanding of vitellogenesis in crustacean species. In the present study, we
      characterized ovarian development under light and electron microscopy and
      examined the hemolymph vitellogenin levels in the coonstriped shrimp, Pandalus
      hypsinotus under laboratory conditions. To measure vitellogenin levels, a time
      resolved fluoroimmunoassay (TR-FIA) was developed after purification of vitellin
      and production of the anti-vitellin antiserum. The TR-FIA showed wide assay range
      (0.98-2000 ng/ml), high sensitivity (0.5 ng/ml), and low assay variability (0.9
      6.4% of intraassay coefficients, 1.4-5.1% for interassay coefficients). Female P.
      hypsinotus had non-vitellogenic ovaries in March after the eggs attached to the
      abdomen hatched, and started yolk accumulation in the ovaries during April
      October. During yolk accumulation, yolk globules appeared and increased in the
      ooplasm. After yolk accumulation, gonadosomatic index (GSI) reached 8.3-8.5 just
      before oviposition. Females spawned and were ovigerous during June-July of the
      next year. Hemolymph vitellogenin levels were low (0.006+/-0.008 mg/ml, mean+/
      SD) before the yolk accumulation, and became significantly higher (2.66 +/-0.93
      mg/ml) during yolk accumulation (GSI, 2-8). Just before oviposition, levels
      declined to low levels (0.040+/-0.012 mg/ml). Vitellogenin levels were
      significantly correlated to GSI during the yolk accumulation. The obtained
      results show that the process of vitellogenesis during the female phase of P.
      hypsinotus is similar to other crustacean species that do not change sex.

PMID- 15514474
TI  - Hormonal control of the orange coloration of diapause pupae in the swallowtail
      butterfly, Papilio xuthus L. (Lepidoptera: Papilionidae).
AB  - Diapause pupae of Papilio xuthus show color polymorphism, represented by diapause
      green, orange, and brownish-orange types that are each associated with specific
      pupation sites. We investigated the role of the site of pupation on the induction
      of the development of orange types (or brownish-orange types), and the endocrine
      mechanism underlying the control of color polymorphism in short-day pupae. All
      short-day larvae of the wandering stage developed into orange or brownish-orange
      type pupae when they were placed in rough-surfaced containers after gut-purge.
      Utilizing a pharate pupal ligation between the thorax and abdomen, the endocrine
      mechanism underlying the control of color polymorphism was shown to involve a
      head-thorax factor (Orange-Pupa-Inducing Factor: OPIF) that induced orange types
      in short-day pupae. OPIF was bioassayed using the ligated abdomens of short-day
      pharate pupae. OPIF was extractable with 2% NaCl solution from 5th-instar larval
      ganglia complexes following the mesothoracic complex (TG(2,3)-AG(1-7)), but it
      could not be extracted with either acetone or 80% ethanol solution. OPIF may not
      exist in the brains of day-0 pupae or in brain-subesophageal ganglion and
      prothoracic ganglion complexes of 5th-instar larvae. The short-day pharate pupae
      responded to OPIF in a dose-dependent manner.

PMID- 15514475
TI  - Molecular evidence of the existence of two sibling species within the
      echinothurioid echinoid Asthenosoma ijimai from Japanese waters.
AB  - The echinoid, Asthenosoma ijimai belonging to the order Echinothurioida from
      Japanese waters shows the geographical variation in morphological and ecological
      characters. The echinothurioid from Ryukyu Islands in southern Japan is cleary
      different from that of Sagami Bay and Suruga Bay in the middle part of Japan at
      non-molecular level. Their phylogenetic and taxonomic relationships were studied
      at the molecular level by allozyme analysis. The results demonstrated that the
      two echinothurioids from Ryukyu Islands and Sagami Bay do not share gene pools
      with each other, and they were fixed for different alleles at five genetic loci
      (Mdh, G6pd, Po, Alk-3 and Est-7) in a total of 23 enzyme genetic loci scored.
      This indicates no gene flow between the two echinothurioids, and is a molecular
      evidence for that they are reproductively isolated and genetically distinct
      species. The Nei's genetic distance (D=0.181) between the two were significantly
      higher than those between conspecific local populations, and comparable to those
      between closely related species in many other animals containing echinoderms. The
      present molecular data are well consistent with the non-molecular evidence from
      morphology, developmental biology and ecology. Putting these data together, we
      propose that the two echinothurioids should be classified as two sibling species
      of the genus Asthenosoma and would like to give the following scientific names:
      the echinothurioid species from Sagami Bay is Asthenosoma ijimai and that from
      Ryukyu Islands is A. ijimai R.

PMID- 15514476
TI  - Freshwater Rhabdocoela (Platyhelminthes) from ephemeral rock pools from Botswana,
      with the description of four new species and one new genus.
AB  - Four new species of freshwater rhabdocoel flatworms from ephemeral rock pools in
      southeastern Botswana are described and discussed. Two of them, Syringoplana
      kolasai n. gen. n. sp. and Mesostoma thamagai n. sp. belong to the Typhloplanidae
      Graff, 1905. The unique construction of the excretory system is the main
      characteristic of S. kolasai. M. thamagai can be separated from other Mesostoma
      Ehrenberg, 1837 species by the presence of a bundle of eosinophilic glands at the
      transition from oviduct to seminal receptacle. The other two taxa, Gieysztoria
      isoldeae n. sp. and G. faubeli n. sp. belong to the Dalyelliidae Graff, 1905. G.
      isoldeae is characterised by the presence of four separate hollow spines in the
      male atrium, which are connected to two accessory glandular organs. G. faubeli
      can be separated from other Gieysztoria Ruebush and Hayes, 1939 species by the
      detailed construction of the stylet. Apart from these two species the occurrence
      of an unidentified Microdalyellia Gieysztor, 1938 species is mentioned.

PMID- 15514477
TI  - Glycosphingolipids-sweets for botulinum neurotoxin.
AB  - A number of viruses, bacteria, and bacterial toxins can only act on cells that
      express the appropriate glycosphingolipids (GSLs) on the outer surface of their
      plasma membranes. An example of this dependency is provided by botulinum
      neurotoxin (BoNT) which is synthesized by Clostridium botulinum and inhibits
      neurotransmission at the neuromuscular junction by catalyzing hydrolysis of a
      SNARE protein, thereby inducing a flaccid paralysis. Haemagglutinin components of
      progenitor forms of BoNT mediate its adherence to glycosphingolipids (GSLs) on
      intestinal epithelial cells while the cellular activity of most isolated
      serotypes requires the presence of certain gangliosides, especially those of the
      Gg1b family. This review discusses available information about the identity and
      the roles of GSLs in the activity of BoNT. Observations that serotypes A-F of
      BoNT require gangliosides for optimum activity (serotype G apparently does not),
      permits the hypothesis that it should be possible to develop an antagonist of
      this interaction thereby inhibiting/reducing its effect.

PMID- 15514478
TI  - Glycosphingolipidoses: beyond the enzymatic defect.
AB  - The glycosphingolipid lysosomal storage diseases are a group of monogenic human
      disorders caused by the impaired catalytic activity of enzymes responsible for
      glycosphingolipid catabolism. Clinical presentation of the diseases is
      heterogeneous, with little obvious correlation between the kind of accumulating
      glycosphingolipid and disease progression or pathogenesis. In this review, we
      discuss clinical symptoms of this group of diseases, and attempt to link disease
      progression and pathology with the biochemical and cellular pathways that may be
      potentially altered in the diseases.

PMID- 15514479
TI  - Susceptibility of cerebellar granule neurons from GM2/GD2 synthase-null mice to
      apoptosis induced by glutamate excitotoxicity and elevated KCl: rescue by GM1 and
      LIGA20.
AB  - Our previous study showed an impaired regulation of Ca(2+) homeostasis in
      cultured cerebellar granule neurons (CGN) from neonatal mice lacking GM2, GD2 and
      all gangliotetraose gangliosides, due to disruption of the GM2/GD2 synthase
      (GalNAc-T) gene. In the presence of depolarizing concentration (55 mM) K(+),
      these cells showed persistent elevation of intracellular Ca(2+) ([Ca(2+)]( i ))
      leading to apoptosis and cell destruction. This was in contrast to CGN from
      normal littermates whose survival was enhanced by high K(+). In this study we
      demonstrate that glutamate has the same effect as K(+) on CGN from these
      ganglioside-deficient knockout (KO) mice and that apoptosis in both cases is
      averted by exogenous GM1. Even more effective rescue was obtained with LIGA20, a
      semi-synthetic derivative of GM1. LC(50) of glutamate in the KO cells was 3.1
      microM, compared to 46 microM in normal CGN. [Ca(2+)]( i ) measurement with fura
      2 revealed no difference in glutamate-stimulated Ca(2+) influx between the 2 cell
      types. However, reduction of [Ca(2+)]( i ) following application of Mg(2+) was
      significantly impaired in the mutant CGN. The rescuing effects of exogenous GM1
      and LIGA20 corresponded to their ability to restore Ca(2+) homeostasis. The
      greater potency of LIGA20 is attributed to its greater membrane permeability with
      resultant ability to insert into both plasma and nuclear membranes at low
      concentration (</=1 microM); GM1 at the same concentration was incorporated only
      into the plasma membrane and required much higher concentration to influence
      Ca(2+) homeostasis and CGN viability.

PMID- 15514480
TI  - Integration of glycosphingolipid metabolism and cell-fate decisions in cancer and
      stem cells: review and hypothesis.
AB  - The metabolism of glycosphingolipids is strictly regulated during the mitotic
      cell cycle. Before the G1-to-S transition, the ceramide and glucosylceramide
      concentration is elevated. Ceramide induces apoptosis synergistically with the
      pro-apoptotic protein prostate apoptosis response 4 (PAR-4) that may be
      asymmetrically inherited during cell division. Only one daughter cell dies
      shortly after mitosis, a mechanism we suggested to regulate the number of neural
      stem cells during embryonic development. The progeny cells, however, may protect
      themselves by converting ceramide to glucosylceramide and other
      glycosphingolipids. In particular, complex gangliosides have been found to
      sustain cell survival and differentiation. The cell cycle may thus be a turning
      point for (glyco)sphingolipid metabolism and explain rapid changes of the
      sphingolipid composition in cells that undergo mitotic cell-fate decisions. In
      the proposed model termed "Shiva cycle", progression through the cell cycle,
      differentiation, or apoptosis may rely on a delicate balance of
      (glyco)sphingolipid second messengers that modulate the retinoblastoma-dependent
      G1-to-S transition or caspase-dependent G1-to-apoptosis program. Ceramide-induced
      cell cycle delay at G0/G1 is either followed by ceramide-induced apoptosis or by
      conversion of ceramide to glucosylceramide, a proposed key regulatory rheostat
      that rescues cells from re-entry into a life/death decision at G1-to-S. We
      propose a mechanistic model for sphingolpid-induced protein scaffolds ("slip")
      that regulate cell-fate decisions and will discuss the biological consequences
      and pharmacological potential of manipulating the (glyco)sphingolipid-dependent
      cell fate program in cancer and stem cells.

PMID- 15514481
TI  - Proteoglycans in brain development.
AB  - Proteoglycans, as part of the extracellular or cell-surface milieu of most
      tissues and organ systems, play important roles in morphogenesis by modulating
      cell-matrix or cell-cell interactions, cell adhesiveness, or by binding and
      presenting growth and differentiation factors. Chondroitin sulfate proteoglycans
      which constitute the major population of proteoglycans in the central nervous
      system may influence formation of neuronal nuclei, establishment of boundaries
      for axonal growth and act as modulators of neuronal outgrowth during brain
      development, as well as during regeneration after injury. There is a paucity of
      information on the role of chondroitin sulfate proteoglycans in central nervous
      system organogenesis. In the chick embryo, aggrecan has a regionally specific and
      developmentally regulated expression profile during brain development. By
      Northern and Western blot analysis, aggrecan expression is first detected in
      chick brain on embryonic day 7 (E7), increases from E7 to E13, declines markedly
      after E16, and is not evident in hatchling brains. The time course and pattern of
      aggrecan expression observed in ventricular zone cells suggested that it might
      play a role in gliogenesis. We have analyzed the role of aggrecan during brain
      development using a aggrecan-deficient model, nanomelia. In nanomelic chicks,
      expression and levels of neurocan and brevican is not affected, indicating a non
      redundant role for these members of the aggrecan gene family. Our analysis of the
      aggrecan-deficient model found a severely altered phenotype which affects cell
      behavior in a neuronal culture paradigm and expression of astrocytic markers in
      vivo . Taken together our results suggest a function for aggrecan in the
      specification of a sub-set of glia precursors that might give rise to astrocytes
      in vivo.

PMID- 15514483
TI  - Characterization of chondroitin sulfate and dermatan sulfate proteoglycans of
      extracellular matrices of human umbilical cord blood vessels and Wharton's jelly.
AB  - The chondroitin sulfate/dermatan sulfate proteoglycans (CS/DSPGs) of the human
      umbilical cord vein, arteries and Wharton's jelly matrices were characterized and
      localized by immunohistochemical analysis. The CS/DSPGs were found to be decorins
      and biglycans with 43-48 kDa core proteins and are distributed throughout the
      umbilical cord. A truncated form of decorin having only the approximately 14 kDa
      NH(2)-terminal portion of the core protein was found exclusively in the vein. The
      proteoglycans, regardless of their locations, have two types of CS/DS chains, one
      with approximately 90% CS and approximately 10% DS and the other with
      approximately 65% CS and approximately 35% DS. The glycosaminoglycan (GAG) chains
      of the truncated decorin consist of approximately 53% CS and approximately 47%
      DS. Both decorin and biglycan including the truncated form of decorin could
      efficiently bind collagen I and fibronectin. The decorin and biglycan with
      approximately 10% DS and approximately 90% CS were loosely bound in the
      extracellular matrices, whereas those with approximately 35% DS bound strongly.
      Together, these data demonstrate that, the GAG chains with 35-47% DS but not
      those with 10% DS, interact strongly with the matrix. Our data also show that the
      GAG chain composition is a significant factor in binding of the decorin and
      biglycan to matrix proteins. The expression of decorin and biglycan with
      distinctively different CS/DS proportions implies specific biological functions
      for these PGs in the umbilical cord. The occurrence of the truncated form of
      decorin exclusively in the umbilical vein suggests a specific functional role.

PMID- 15514484
TI  - Chemo-enzymatic synthesis and structure-activity study of artificially N
      glycosylated eel calcitonin derivatives with a complex type oligosaccharide.
AB  - Starting from N-glycosylated eel calcitonin derivatives that contain an N-acetyl
      D-glucosamine residue specifically at the 3rd, 14th, 20th or 26th amino acid
      residue, corresponding glycopeptides with a complex-type oligosaccharide attached
      to the respective amino acid residue were synthesized by means of a
      transglycosylation reaction catalyzed by an endo-beta-N-acetylglucosaminidase
      from Mucor hiemalis . The use of a recombinant enzyme and an excess of a glycosyl
      donor led to a yield in excess of 60%. Calcitonin derivatives containing
      truncated oligosaccharides were also prepared via digestion of the complex-type N
      glycan with exoglycosidases. Using these N-glycosylated calcitonin derivatives,
      the effect of carbohydrate structure and glycosylation site on the three
      dimensional structure and the biological activity of the peptide were studied.
      The conformation of the peptide backbone did not change irrespective of the
      carbohydrate structure or the glycosylation site. However, hypocalcemic activity,
      calcitonin-receptor binding activity and the biodistribution of the derivatives
      were affected by the glycosylation and were dependent on both the carbohydrate
      structure and the glycosylation site. Although the larger oligosaccharides tended
      to hinder receptor binding, the biodistribution altered by N-glycosylation
      appeared to enhance the hypocalcemic activity in some cases, and the magnitude of
      the effect was dependent on the site of glycosylation.

PMID- 15514482
TI  - Comparing N-glycan processing in mammalian cell lines to native and engineered
      lepidopteran insect cell lines.
AB  - In the past decades, a large number of studies in mammalian cells have revealed
      that processing of glycoproteins is compartmentalized into several subcellular
      organelles that process N-glycans to generate complex-type oligosaccharides with
      terminal N -acetlyneuraminic acid. Recent studies also suggested that processing
      of N-glycans in insect cells appear to follow a similar initial pathway but
      diverge at subsequent processing steps. N-glycans from insect cell lines are not
      usually processed to terminally sialylated complex-type structures but are
      instead modified to paucimannosidic or oligomannose structures. These differences
      in processing between insect cells and mammalian cells are due to insufficient
      expression of multiple processing enzymes including glycosyltransferases
      responsible for generating complex-type structures and metabolic enzymes involved
      in generating appropriate sugar nucleotides. Recent genomics studies suggest that
      insects themselves may include many of these complex transferases and metabolic
      enzymes at certain developmental stages but expression is lost or limited in most
      lines derived for cell culture. In addition, insect cells include an N 
      acetylglucosaminidase that removes a terminal N -acetylglucosamine from the N
      glycan. The innermost N -acetylglucosamine residue attached to asparagine residue
      is also modified with alpha(1,3)-linked fucose, a potential allergenic epitope,
      in some insect cells. In spite of these limitations in N-glycosylation, insect
      cells have been widely used to express various recombinant proteins with the
      baculovirus expression vector system, taking advantage of their safety, ease of
      use, and high productivity. Recently, genetic engineering techniques have been
      applied successfully to insect cells in order to enable them to produce
      glycoproteins which include complex-type N-glycans. Modifications to insect N
      glycan processing include the expression of missing glycosyltransferases and
      inclusion of the metabolic enzymes responsible for generating the essential donor
      sugar nucleotide, CMP- N -acetylneuraminic acid, required for sialylation.
      Inhibition of N -acetylglucosaminidase has also been applied to alter N-glycan
      processing in insect cells. This review summarizes current knowledge on N-glycan
      processing in lepidopteran insect cell lines, and recent progress in
      glycoengineering lepidopteran insect cells to produce glycoproteins containing
      complex N-glycans.

PMID- 15514485
TI  - Community- and hospital-acquired pneumonia-the role of the hospitalist in
      improving outcomes and reducing resource utilization.

PMID- 15514486
TI  - Antibiotic-resistant pathogens-epidemiology and clinical relevance.

PMID- 15514487
TI  - Identifying strategies to improve outcomes and reduce costs-a role for the
      hospitalist.

PMID- 15514488
TI  - Recommendations for management of community- and hospital-acquired pneumonia-the
      hospitalist perspective.

PMID- 15514492
TI  - Community-acquired pneumonia-optimizing antibiotic usage.

PMID- 15514493
TI  - Hospital-acquired pneumonia-evolving knowledge.

PMID- 15514494
TI  - Treadmill versus shuttle walk tests of walking ability in intermittent
      claudication.
AB  - PURPOSE: To compare treadmill and shuttle walk tests for assessing functional
      capacity in patients with intermittent claudication, with respect to test-retest
      reliability, cardiovascular responses, and patient preferences. METHODS: Patients
      with stable intermittent claudication (N = 55, ages 52-85 yr, median age 68 yr)
      were recruited from the Sheffield Vascular Institute at the Northern General
      Hospital, Sheffield, UK. Each patient performed an incremental shuttle walk test,
      a constant-pace shuttle walk test, and a standardized treadmill test (3.2 km x h(
      1), 12% gradient), each on three occasions. The incremental shuttle walk began at
      3 km x h(-1) and increased by 0.5 km x h(-1) every minute, whereas the constant
      pace shuttle walk was performed at the fixed pace of 4 km x h(-1). Claudication
      distance (CD), maximum walking distance (MWD), heart rate (HR), and blood
      pressure were assessed in each testing session. The patients also completed a
      test preference questionnaire. RESULTS: CD and MWD for both shuttle walks were
      greater than the corresponding walking distances achieved in the treadmill test
      (P < 0.001). Average coefficients of variation for repeated incremental shuttle
      walk, constant-pace shuttle walk, and treadmill tests were 15.9%, 21.1%, and
      18.7%, respectively, for MWD, corresponding to average intraclass correlation
      coefficients of 0.87, 0.82, and 0.87. Treadmill walking evoked greater increases
      in HR and blood pressure (P < 0.001), and fewer patients expressed a preference
      for it (24 vs 43% for shuttle walking). CONCLUSION: These findings indicated that
      shuttle walk testing exhibits similar test-retest reliability as treadmill
      testing, but that it evoked a lower level of cardiovascular stress and is
      preferred to treadmill testing by a large proportion of patients.

PMID- 15514495
TI  - Immediate Achilles tendon response after strength training evaluated by MRI.
AB  - PURPOSE: To evaluate the tendon response after acute strength training in chronic
      Achilles tendinosis using magnetic resonance imaging (MRI). METHODS: Twenty-two
      patients (44 Achilles tendons, 15 males, 8 patients with bilateral symptoms) with
      a median age of 45 yr (range 28-57 yr) were included in the study. In all
      patients, both Achilles tendons were examined with MRI before and immediately
      after a standardized training program. The most painful side underwent 6 sets and
      15 repetitions of heavy-loaded eccentric training. The contralateral tendons
      underwent only concentric loading during the training program. The tendon volume
      and the intratendinous signal were evaluated and calculated by MRI using a seed
      growing technique. RESULTS: The immediate response of eccentric loading on the
      symptomatic tendons resulted in a 12% increase of the tendon volume, evident on
      T2-WI, from 7.8 +/- 2.0 to 8.8 +/- 2.7 cm3 (P < 0.001), and a 31% increase of the
      intratendinous signal evident on PD-WI, from 221 +/- 74 to 278 +/- 78 signal
      units (SU) (P < 0.001). The corresponding sequences on the contralateral
      concentrically loaded tendons showed an increase of 17% of tendon volume, from
      6.1 +/- 1.5 to 7.0 +/- 1.6 cm3 (P < 0.001), and an increase of 27% of the
      intratendinous signal, from 170 +/- 55 to 211 +/-57 SU (P < 0.001). There was no
      significant difference of the mean of the increased tendon volume and the
      intratendinous signal between the eccentrically heavily loaded symptomatic
      tendons and the concentrically loaded contralateral tendons. CONCLUSIONS: Both
      eccentric and concentric loading of the Achilles tendon resulted in increased
      total tendon volume and intratendinous signal. This increase may be explained by
      a higher water content and/or hyperemia in the Achilles tendon during and/or
      immediately after strength training of the gastrocnemius-soleus complex.

PMID- 15514496
TI  - Montelukast has no ergogenic effect on cycle ergometry in cold temperature.
AB  - PURPOSE: To examine the effects of a single 10-mg dose of ML on physical
      performance in EIB- and EIB+ athletes. METHODS: Twenty-four male college ice
      hockey players performed two 6-min maximal work accumulation bouts on an
      electronically braked cycle ergometer in subfreezing conditions (-2.5 +/- 0.4
      degrees C) 6-8 h after either ML or placebo (PL) to obtain total work accumulated
      (kJ); subjects were evaluated for EIB after each exercise trial. RESULTS: Eight
      (33%) subjects were identified as EIB+ (23.5 +/- 13.35% fall in FEV1); 16 were
      EIB- (1.8 +/- 3.03% fall in FEV1). ML provided an approximately 50% protection
      against postexercise fall in FEV1. No significant differences in kJ were found
      between PL and ML trials for pooled subjects (95.3 +/- 13.69 and 94.8 +/- 13.27
      kJ, respectively), EIB- subjects (99.6 +/- 13.26 and 99.0 +/- 11.81 kJ,
      respectively), or EIB+ subjects (86.8 +/- 10.67 and 86.5 +/- 12.72 kJ,
      respectively). Total work accumulated for EIB- subjects was significantly greater
      than for EIB+ subjects for both PL and ML (P < 0.05). CONCLUSION: A single 10-mg
      dose of ML had no ergogenic effect for EIB- and EIB+ subjects performing short
      duration high-intensity exercise in subfreezing temperature, supporting the use
      of ML as EIB prophylaxis during international sport competition.

PMID- 15514497
TI  - Acute on chronic subdural hematoma in a female boxer: a case report.
AB  - INTRODUCTION: Although the sport of female boxing has a long history, the
      activity's current popularity is unprecedented. As more women participate, we can
      expect them to experience many of the serious neurologic injuries observed in
      their male counterparts. We present the first reported subdural hematoma in a
      female secondary to boxing and critique management decisions made by the
      athlete's trainer/coach. CASE REPORT: A 24-yr-old right-handed female boxer
      developed headaches of increasing intensity, nausea, and emesis after being
      knocked down while sparring. She was allowed to continue training despite
      persistent symptoms and participated in a match 2 wk after the incident that was
      stopped due to intolerable headache. Computed tomography scan of the brain
      revealed a large heterogeneous subdural fluid collection over the left cerebral
      hemisphere, causing effacement of the adjacent sulci and a large left-to-right
      midline shift, consistent with an acute on chronic subdural hematoma. After
      surgical evacuation, the patient reported persistent memory, concentration, and
      language problems. Neuropsychological evaluation was performed and revealed
      deficits in confrontational naming, information retrieval, and concentration
      difficulty. DISCUSSION: Several factors may increase the female participants'
      risk for acute neurological injury. The activity's current popularity and high
      demand with fans results in rapid advancement of inexperienced fighters, which
      leads to dangerous mismatches. Intergender sparring is common, and return to
      competition guidelines utilized for male participants are often not adhered to.
      This report is timely in that female athletes are more often crossing into
      previously male dominated sports and should serve as a reminder that these
      participants are vulnerable to similar injuries. Previous safety guidelines
      should be utilized in this new population of participants.

PMID- 15514498
TI  - Reduced amount and disrupted temporal pattern of spontaneous exercise in diabetic
      rats.
AB  - INTRODUCTION/PURPOSE: The beneficial effects of exercise for subjects with
      diabetes or prediabetic states are well established. However, the converse, that
      is, the effect of diabetes on spontaneous exercise performance, is not as well
      defined. Mice with mdx muscular dystrophy not only reduce total spontaneous
      running distance, but also decrease the duration of periods during which they are
      active, suggesting a defect in endurance. Studies tested the hypothesis that Type
      I diabetes causes similar changes in spontaneous exercise performance. METHODS:
      Wistar rats received streptozotocin to produce a model of Type I diabetes or
      buffer alone, and had access to running wheels for the next 8 wk. RESULTS:
      Diabetic rats had elevated serum glucose levels (689 +/- 85 vs 270 +/- 21 mg x
      dL(-1), P = 0.0003) but normal serum bicarbonate levels. After 8 wk, diabetic
      rats were running for considerably lower distances than normal animals (daily
      distance 182 +/- 58 vs 4981 +/- 1373 m, P = 0.006). Furthermore, the average
      consecutive running time was much shorter in diabetic than normal rats (16 +/- 1
      vs 40 +/- 6 min, P = 0.004). Differences in running behavior between diabetic and
      normal mice were absent early after injection of streptozotocin, but were fully
      established by week 4 for both total distance and consecutive running times.
      CONCLUSION: Severe untreated Type I diabetes in rats reduces spontaneous exercise
      in a manner similar to that seen in mdx mouse muscular dystrophy, with reduced
      running distance and consecutive running times.

PMID- 15514499
TI  - Exercise attenuates diabetes-induced ultrastructural changes in rat cardiac
      tissue.
AB  - INTRODUCTION/PURPOSE: Exercise is an effective nonpharmacological treatment in
      the prevention of mortality and morbidity due to cardiovascular disease in Type I
      diabetes. This study sought to explore the effects of endurance exercise on the
      ultrastructural changes seen in diabetic cardiomyopathy. METHODS: Seven-week-old
      rats were divided into three groups consisting of sedentary nondiabetic control,
      sedentary diabetic, and exercised diabetic animals. Diabetes was induced using
      streptozotocin injection, and the exercised animals were run daily on a treadmill
      for 9 wk. Changes in heart ultrastructure were analyzed using transmission
      electron microscopy. RESULTS: Ultrastructural changes in the left ventricle
      produced by diabetes included changes in myofibrillar arrangements, disrupted
      mitochondria, and increased cytoplasmic area with an increase in lipid amounts
      and an increase in individual collagen fiber cross-sectional surface area. Also,
      an increase in heterochromatin lining the nuclear envelope and an increase in
      invaginations of the nuclear membrane were observed in cardiomyocytes from
      diabetic rats when compared with the nuclei from nondiabetic cells. Exercise was
      found to significantly attenuate the diabetes-induced changes in collagen
      fibrils, cytoplasmic area, and level of mitochondrial disruption. In contrast,
      exercise did not appear to significantly influence myofibril volume density,
      lipid accumulation, or nuclear deformities. CONCLUSION: These findings indicate
      that exercise restores specific ultrastructural characteristics of diabetic
      cardiomyopathy returning them toward nondiabetic phenotypes, particularly in the
      mitochondria and extracellular matrix proteins.

PMID- 15514500
TI  - Atrioventricular plane displacement in untrained and trained females.
AB  - PURPOSE: Female athletes often demonstrate changes in cardiac dimensions that are
      less prominent than in male athletes, and results from longitudinal studies are
      conflicting. The atrioventricular plane displacement (AVPD) in the heart is used
      as an index of left ventricular systolic function with the assumption that it is
      a more sensitive method for measuring myocardial contractility compared with left
      ventricular ejection fraction. The aim of the present study was to determine the
      effect of a short period of endurance training on cardiac dimensions in sedentary
      female subjects and to measure the AVPD at rest and during submaximal workload.
      METHODS: Twelve sedentary female subjects (21.9 +/- 1.3 yr, 168.8 +/- 3.5 cm,
      64.0 +/- 6.6 kg, and 42.6 +/- 2.9 mL x kg(-1) x min(-1) in maximal oxygen uptake)
      were examined with echocardiography before and after a period of interval
      training (varying from 2 to 5 min at 90-95% of maximal heart rate, 3 d x wk(-1),
      8 wk). RESULTS: Maximal oxygen uptake increased by 18% to 50.4 +/- 3.1 mL x kg(
      1) x min(-1) (P < 0.001). Left ventricular mass increased from 123.9 to 139.2 g
      (P = 0.007). There was a significant increase in posterior wall thickness but no
      change in cavity size. The AVPD did not change at rest but increased
      significantly from 15.6 to 17.6 mm (P < 0.001) during exercise at 85-90% of
      maximal heart rate. CONCLUSION: This study shows that a short period of aerobic
      endurance training induces changes in the female heart, both in cardiac
      dimensions at rest and in left ventricular systolic function at submaximal
      workload. AVPD during submaximal exercise discriminate well between the untrained
      and trained healthy heart.

PMID- 15514501
TI  - TLR4 is lower in resistance-trained older women and related to inflammatory
      cytokines.
AB  - INTRODUCTION/PURPOSE: Regular exercise may offset age-associated increases in
      inflammatory cytokines and reduce the risk of developing diseases with an
      inflammatory etiology by exerting "anti-inflammatory" effects. Toll-like receptor
      4 (TLR4) signaling stimulates inflammatory cytokine production, and may explain
      the "anti-inflammatory" effect attributed to regular exercise. Therefore, the
      purpose of the present study was to compare the effect of acute (3 sets, 9
      exercises, 10 repetitions at 80% of the 1-repetition maximum) and chronic
      resistance exercise on TLR4 and inflammatory cytokines. METHODS: Venous blood
      samples were collected from trained (TR, N = 10) and untrained (UT, N = 10) older
      (65-80 yr) postmenopausal women: before (PRE), immediately post (POST), and 2 h
      (2H), 6 h (6H), and 24 h (24H) after completion of exercise. Cell-surface
      expression of TLR4 (two-color immunofluorescent cytometry), LPS (25 microg x mL(
      1))-stimulated cytokine production (ELISA), plasma cytokines (ELISA), and mRNA
      expression of TLR4 and cytokines (RT-PCR) were determined for each sample.
      RESULTS: TR had 124% less cell-surface TLR4 expression than UT (P < 0.05). A
      significant time effect was found for LPS-stimulated IL-6, IL-1beta, and TNF
      alpha, where 6H was significantly greater than all other samples. No significant
      effects were found for plasma (IL-6 and TNF-alpha) or mRNA expression (IL-6, TNF
      alpha, and IL-1beta) of inflammatory cytokines. When subjects were grouped
      according to cell-surface TLR4 expression (HI and LO), LPS-stimulated TNF-alpha
      (302%), IL-1beta (209%), and IL-6 (167%) production was greater for HI than LO (P
      < 0.05). CONCLUSION: Regularly exercising older women expressed less cell-surface
      TLR4 but did not have lower plasma levels or produce less LPS-stimulated
      inflammatory cytokines at rest or in response to a single bout of resistance
      exercise. TLR4 changes may explain the "anti-inflammatory" effect that has
      recently been attributed to chronic (2x wk for previous 24 months) resistance
      exercise training.

PMID- 15514502
TI  - Temporal changes in tPA and PAI-1 after maximal exercise.
AB  - PURPOSE: Although fibrinolysis increases with acute exercise, it decreases
      rapidly during the postexercise period. Therefore, the time point at which blood
      samples are collected postexercise could affect reported tissue plasminogen
      activator (t-PA) and/or plasminogen activator inhibitor-1 (PAI-1) levels. The
      purpose of this study was to determine the time course of t-PA and PAI-1 changes
      after acute maximal exercise. METHODS: Eight healthy males performed a graded
      maximal exercise test on a treadmill. Venous blood samples were collected using
      an indwelling catheter before exercise and at 1, 2, 4, 6, 8, and 10 min
      postexercise. Mean differences in t-PA activity, t-PA antigen, and PAI-1 activity
      at each time point were assessed using a repeated measures ANOVA. Post hoc means
      comparisons were performed by contrasting the 1-min postexercise value against
      all other time points. RESULTS: Both t-PA activity and t-PA antigen significantly
      increased from pre- to postexercise (P < 0.05). t-PA activity did not change from
      1 to 2 min postexercise but decreased significantly at 4 min postexercise.
      Likewise, t-PA antigen remained elevated from 1 to 2 min postexercise but
      decreased at 4 min postexercise. PAI-1 decreased from pre- to postexercise but
      did not change during the 10-min postexercise period. CONCLUSION: To accurately
      evaluate the t-PA response to acute exercise, blood samples should be collected
      within 2 min after the cessation of exercise.

PMID- 15514503
TI  - Effect of FIO2 on oxidative stress during interval training at moderate altitude.
AB  - PURPOSE: To evaluate the effect of different fractions of inspired oxygen (FIO2)
      on oxidative stress during a high-intensity interval workout in trained endurance
      athletes residing at altitude. METHODS: Subjects (N = 19) were trained male
      cyclists who were residents of moderate altitude (1800-1900 m). Testing was
      conducted at 1860 m (PB 610-612 torr, PIO2 approximately 128 torr). Subjects
      performed three randomized, single-blind trials consisting of a standardized
      interval workout (6 x 100 kJ) while inspiring a medical-grade gas with FIO2 0.21
      (PIO2 approximately 128 torr), FIO2 0.26 (PIO2 approximately 159 torr), and FIO2
      0.60 (PIO2 approximately 366 torr). Serum lipid hydroperoxides (LOOH) and whole
      blood reduced glutathione (GSH) were measured 60 min preexercise and immediately
      postexercise, and analyzed using standard colorimetric assays. Urinary
      malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) were measured 24 h
      preexercise and 24 h postexercise, and analyzed via HPLC and ELISA, respectively.
      RESULTS: Compared with the control trial (FIO2 0.21), total time (min:s) for the
      100-kJ work interval was faster (5% in FIO2 0.26; 8% in FIO2 0.60 (P < 0.05)) and
      power output (W) was higher (5% in FIO2 0.26, 8% in FIO2 0.60 (P < 0.05)) in the
      supplemental oxygen trials. There was a significant pre- versus postexercise main
      effect (P < 0.05) for LOOH and GSH; however, there were no significant
      differences in LOOH or GSH between the FIO2 trials. MDA and 8-OHdG were
      unaffected by either the interval training session or FIO2. CONCLUSION:
      Supplemental oxygen used in conjunction with high-intensity interval training at
      altitude ("live high + train low via supplemental O2" (LH + TLO2)) results in a
      significant improvement in exercise performance without inducing additional free
      radical oxidative stress as reflected in hematological and urinary biomarkers.

PMID- 15514504
TI  - Effects of sodium bicarbonate on VO2 kinetics during heavy exercise.
AB  - PURPOSE: Sodium bicarbonate was used to investigate the effect of blood pH on VO2
      kinetics during heavy exercise. METHODS: On separate days, 10 active subjects
      performed two 6-min cycling bouts (208 +/- 12 W) at 25 W above their ventilatory
      threshold. Each subject ingested 0.3 g x kg(-1) of sodium bicarbonate with
      approximately 1 L of water or water alone 1 h before exercise. VO2 kinetics were
      examined by means of a three-component mono-exponential model. RESULTS:
      Bicarbonate ingestion caused a significant increase in the preexercise blood pH
      (7.512 +/- 0.009 vs 7.425 +/- 0.007; P < 0.001). In the bicarbonate trial, the
      time constant for the rapid component (27.9 +/- 3.5 s) was slower than the
      control trial (20.8 +/- 2.4 s; P = 0.017). The higher blood pH after bicarbonate
      ingestion would have diminished local blood flow and caused a leftward shift of
      the oxygen-hemoglobin dissociation curve both of which would slow oxygen delivery
      to working muscle. In addition, bicarbonate ingestion diminished the amplitude of
      the slow component 29% (463 +/- 43 vs 649 +/- 53 mL x min(-1); P = 0.040). The
      primary cause of the slow component during heavy exercise is fatigue of working
      fibers and an accompanying increase of motor unit recruitment. Elevated plasma
      bicarbonate concentration is reported to stimulate the efflux of H from muscle
      fibers and to increase intramuscular pH. CONCLUSIONS: The slower time constant
      during the rapid component suggested that oxygen delivery is a limiting factor of
      VO2 kinetics during the onset of heavy exercise. Also, these results imply that
      bicarbonate ingestion diminished fatigue in working fibers during the slow
      component.

PMID- 15514505
TI  - Eccentric cycle exercise: training application of specific circulatory
      adjustments.
AB  - PURPOSE: Despite identical oxygen uptake (VO2), enhanced heart rate (HR) and
      cardiac output (Q) responses have been reported in eccentric (ECC) versus
      concentric (CON) cycle exercise. The aim of this study was to describe the
      specific circulatory adjustments (HR and stroke volume (SV)) to incremental ECC
      cycle exercise in order to: 1) determine the HR values leading to identical VO2
      in ECC and CON cycling; and 2) estimate the interindividual variability of this
      HR correspondence between the two exercise modes, with emphasis upon
      rehabilitation and training purposes. METHODS: Eight healthy male subjects (age,
      28 +/- 2 yr) participated in this study. They performed CON and ECC cycle
      incremental exercises (power output increases of 50 W every 3 min). Breath-by
      breath gas exchange analysis and beat-by-beat thoracic impedancemetry were used
      to determine VO2 and Q, respectively. RESULTS: At the same metabolic power (VO2
      of 1.08 +/- 0.05 L x min(-1) in CON vs 1.04 +/- 0.06 L x min in ECC), SV was not
      different, but HR was 17% higher in ECC (P < 0.01), leading to a 27% enhanced Q
      (P < 0.01). Q and HR net adjustments (exercise minus resting values) in ECC
      versus CON muscle involvement demonstrated important interindividual variability
      with coefficients of variation amounting to 32% and 30%, respectively.
      CONCLUSION: In practice, if a given level of VO2 is to be reached, ECC HR has to
      be set above the CON one. Taking into account the interindividual variability of
      the circulatory adjustments in ECC versus CON muscle involvement, a precise HR
      correspondence can be established individually from the VO2/HR relationship
      obtained using ECC incremental testing, allowing prescription of accurate target
      HR for rehabilitation or training purposes.

PMID- 15514507
TI  - Mechanomyographic responses of the vastus medialis to isometric and eccentric
      muscle actions.
AB  - PURPOSE: The mechanomyographic (MMG) signal may be used to examine the motor
      control strategies used to modulate torque during various types of muscle
      actions. Therefore, the purpose of this study was to examine the MMG amplitude
      and mean power frequency (MPF) versus torque relationships during isometric and
      eccentric isokinetic muscle actions. METHODS: Eleven adults (mean age +/- SD =
      20.8 +/- 1.4 yr) volunteered to perform isometric and eccentric isokinetic leg
      extension muscle actions at 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100% of peak
      torque on a Cybex 6000 dynamometer. A piezoelectric crystal contact sensor was
      placed on the vastus medialis to detect the MMG signal. RESULTS: Polynomial
      regression analyses indicated that for the isometric muscle actions, the
      relationships for MMG amplitude (r2 = 0.984) and MPF (r2 = 0.989) versus torque
      were linear. For the eccentric isokinetic muscle actions, the relationships for
      MMG amplitude (r2 = 0.580) and MPF (r2 = 0.961) versus torque were also linear.
      CONCLUSION: The patterns for MMG amplitude and MPF may reflect the motor control
      strategies that modulate torque production for isometric and eccentric isokinetic
      muscle actions. Based on the results of this and previous studies, it appears
      that for the vastus medialis, torque is modulated in a similar manner for
      isometric, concentric, and eccentric isokinetic muscle actions. Specifically,
      these findings suggest that gradation of torque involves increases in recruitment
      and firing rate to 100% voluntary torque production.

PMID- 15514506
TI  - Effects of recovery modes after knee extensor muscles eccentric contractions.
AB  - PURPOSE: This study aimed to evaluate the benefit of using low-intensity running
      or electromyostimulation (EMS) to hasten the recovery process from eccentric
      contraction-induced injury. METHODS: Before and 30 min, 24 h, 48 h, and 96 h
      after a one-legged downhill run, electrical stimulations were applied to the
      femoral nerve of healthy volunteers. Superimposed twitches were delivered during
      isometric maximal voluntary contraction (MVC) to determine the voluntary
      activation level (%VA). For 4 d after the exercise, each subject performed either
      (i) 30 min of running at 50% VO2max, (ii) 30 min of low-frequency EMS on the
      lower limb extensor muscles, or (iii) passive recovery. RESULTS: Recovery time
      courses of the different variables did not differ significantly among the three
      experimental conditions. MVC decreased 30 min after the exercise and did not
      recover thereafter (P < 0.001). Percent VA was depressed after the exercise (P <
      0.05) but did not contribute to MVC decrement thereafter. Mechanical responses to
      80- and 20-Hz stimulation (P80 and P20, respectively) were significantly reduced
      over time (P < 0.01 and P < 0.001, respectively). Interestingly, MVC, P20, and
      P80 decrements were not statistically different (-9.6 +/- 14.5%, -13.2 +/- 14.2%,
      and -12.3 +/- 11.3%, respectively) at 48 h, and the P20.P80(-1) ratio showed
      complete recovery at this time. CONCLUSIONS: The different recovery modes had no
      significant effect on the recovery time course of contractile properties. The
      prolonged torque loss is mainly due to peripheral alterations. Our results
      suggest that an alteration of the excitation-contraction coupling might be
      involved during the first 2 d after the eccentric exercise. From 2 to 4 d, damage
      to force-generating structures could account for the remaining torque deficit.

PMID- 15514508
TI  - Physical activity and mortality across cardiovascular disease risk groups.
AB  - PURPOSE: Several cohort studies suggest that sedentary individuals have an
      increased risk of death compared with individuals who are physically active. Most
      of these studies have been conducted in highly selected patient populations who
      tend to be healthier and are from higher socioeconomic status (SES) groups. We
      examined the impact of a sedentary lifestyle on mortality by cardiovascular
      disease (CVD) risk group in a national sample of U.S. adults who represent a wide
      range of activity levels, health conditions, and SES groups. METHODS: Using data
      from the HRS, a nationally representative, observational study of 9824 U.S.
      adults aged 51-61 yr in 1992, we estimated the relative risk of death comparing
      sedentary individuals with those who are physically active by CVD risk group in a
      multivariate logistic regression model. RESULTS: Even after adjusting for
      confounders, regular moderate to vigorous physical activity was associated with
      substantially lower overall mortality (odds ratio (OR) = 0.62 (95% CI 0.44-0.86))
      compared with sedentary individuals. High CVD risk individuals (21% of the
      population) accounted for 64% of deaths attributable to a sedentary lifestyle.
      Those with high CVD risk had the most significant benefit from being active
      (regular moderate to vigorous exercisers OR = 0.55 (95% CI 0.31-0.97) and
      occasional or light exercisers OR 0.55 (95% CI 0.41-0.74)) compared with high CVD
      risk individuals who were sedentary. CONCLUSION: A sedentary lifestyle is
      associated with a higher risk of death in preretirement-aged U.S. adults.
      Individuals with high CVD risk appear to get the largest benefit from being
      physically active. Physical activity interventions targeting high CVD risk
      individuals should be a medical and public health priority.

PMID- 15514509
TI  - Adolescent correlates of adult physical activity: a 26-year follow-up.
AB  - PURPOSE: It is hypothesized that adolescent physical activity, fitness,
      anthropometric dimensions, fatness, biological maturity, and family
      characteristics contribute to the variation in physical activity at 40 yr of age,
      and that these associations vary with age. METHODS: Subjects were 166 males
      followed from 1969 to 1996, between the ages of 14 and 40 yr from the Leuven
      Longitudinal Study on Lifestyle, Fitness and Health. Sports participation,
      fitness, anthropometric dimensions, fatness, and biological maturity were
      observed during the growth period. Also, sociocultural characteristics of the
      family were examined. The work, leisure time, and sport activity index of the
      Baecke Questionnaire and activity counts of a triaxial accelerometer were used as
      outcome variables at 40 yr. RESULTS: When upper and lower activity groups
      (quintiles) at 40 yr were contrasted, moderate associations were found (R2c
      varied between 0.1419 and 0.3736). No or low associations were found with the
      leisure time index. Body dimensions, fitness scores, sports practice, and family
      characteristics contributed to the explained variance in work, sport index, and
      activity counts. Multiple correlations were low (R2 = 0.037-0.085) for the work
      and leisure time activities, and were somewhat higher (R2 = 0.06-0.156) for the
      sport index and the activity counts in the total sample. CONCLUSION: Adolescent
      somatic dimensions, fitness, sports participation, parental sociocultural
      characteristics, and sport participation contributed to a small-to-moderate
      extent to the contrast between high and low active adults.

PMID- 15514510
TI  - Tracking of physical activity from childhood to adulthood.
AB  - PURPOSE: To examine 1) relationships between adult PA at 35 yr and PA as a child,
      and 2) the influence of enhanced primary school physical education (physed+) and
      of parental PA upon the long-term tracking of PA in the offspring. METHODS: PA
      data from the 1970-1977 Trois-Rivieres Growth and Development Study, completed
      when the children were aged 10-12 yr, were compared with PA data collected on 166
      of the same subjects in 1996-1998, when aged 34.9 +/- 1.1 yr. The weekly duration
      of total PA, intense PA, light PA, organized PA, and total sedentary behaviors
      other than sleep as a child were each correlated with a questionnaire assessment
      of total weekly PA as an adult. RESULTS: Considering males and females jointly,
      adult PA showed a significant but weak association with childhood PA,
      correlations for total PA, intense PA, light organized PA, and nonorganized PA
      amounting to r = 0.20, 0.18, 0.12, and 0.19, respectively. In males (N = 79), the
      total time spent during childhood in organized PA was associated with adult PA (r
      = 0.26, P < 0.05), due to students who received physed+ (r = 0.34). In females,
      also, a higher PA frequency as an adult was significantly associated with
      physed+. There was no association of PA patterns between children and their
      parents. CONCLUSION: Our results suggest a positive impact of early required
      physical education upon adult PA but provide little evidence of an overall
      association between time spent in other categories of PA during childhood and PA
      as an adult.

PMID- 15514511
TI  - Passive force, angle, and stiffness changes after stretching of hamstring
      muscles.
AB  - Periodic or long-term stretching programs have demonstrated changes in joint
      range of motion. The suggested mechanisms for these increases in range of motion
      are changes in the tissue properties of the muscle and more recently stretch
      tolerance. However, few studies have examined changes in passive resistive forces
      and related these changes to increases in range of motion. PURPOSE: The purpose
      of this study was to investigate the influence of a 6-wk hamstring-stretching
      program on knee extension range of motion, passive resistive forces, and muscle
      stiffness. METHODS: A randomized control trial with repeated measures was
      undertaken with 43 school-age subjects. Hamstring extensibility was assessed by a
      passive knee extension test using a Kincom isokinetic dynamometer. The
      intervention group participated in a 6-wk hamstring-stretching program. Stretches
      were performed 5 d x wk(-1), once per day, held for 30 s, and for 3 repetitions.
      The control group did not stretch over the 6-wk intervention period. Measurements
      of hamstring extensibility were repeated at the end of the 6-wk intervention.
      RESULTS: After the intervention period, significant (P < 0.05) increases in knee
      extension range of motion, passive resistive force, and stiffness were observed
      in the experimental group. No significant differences were observed in the
      control group's findings for the same variables. CONCLUSIONS: The findings of
      this study are consistent with other literature that shows periodic stretching
      programs over a 6-wk time frame produce significant changes in knee extension
      range of motion. The finding of increased stiffness in the new range of motion,
      gained as a result of the stretching program, provides some evidence that
      structural changes had occurred in the stretched muscles.

PMID- 15514512
TI  - Model prediction of anterior cruciate ligament force during drop-landings.
AB  - PURPOSE: The aim of this study was to calculate and explain the pattern of force
      transmitted to the anterior cruciate ligament during soft-style drop-landings. We
      hypothesized that peak ACL loading is due to the anterior pull of the quadriceps
      on the tibia, as these muscles develop large eccentric forces upon impact.
      METHODS: A three-dimensional model of the body was used to simulate drop-landing.
      The simulation was performed by entering into the model muscle excitation
      patterns based on experimental EMG. The input excitation patterns were modified
      to create a performance response of the model that matched experimental data.
      Joint angles, ground reaction forces, and muscle forces obtained from the landing
      simulation were then applied to a model of the lower limb that incorporated a
      three-dimensional model of the knee. RESULTS: The model ACL was loaded only in
      the first 25% of the landing phase. Peak ACL force (approximately 0.4 BW)
      resulted from a complex interaction between the patellar tendon force, the
      compressive force acting at the tibiofemoral joint, and the force applied by the
      ground to the lower leg. The patellar tendon force and tibiofemoral contact force
      both applied significant anterior shear forces to the shank throughout the
      landing phase. These effects were modulated by another significant posterior
      shear force applied by the ground reaction, which served to limit the maximum
      force transmitted to the ACL. CONCLUSION: The pattern of ACL force in drop
      landing cannot be explained by the anterior pull of the quadriceps force alone.

PMID- 15514513
TI  - An isokinetic profile of trunk rotation strength in elite tennis players.
AB  - PURPOSE: The changes in stroke production in the modern game of tennis have
      increased the demands on trunk rotation in elite tennis players. Unlike the
      shoulder, where unilateral strength adaptations have been identified, no study to
      date has objectively quantified side to side rotational trunk strength in elite
      tennis players. METHODS: One hundred nine elite tennis players were tested using
      a Cybex isokinetic torso rotation unit at 60 and 120 degrees x s(-1) to measure
      left and right rotation while stabilized in a seated position. A repeated
      measures ANOVA was used with post hoc dependent t-tests where main effect
      differences were identified to determine side to side rotational differences.
      RESULTS: No significant difference in trunk rotation strength was measured in the
      elite male players. Peak torque to body weight ratios averaged 63.7 and 57.5% for
      forehand rotation (left rotation in right-handed player) and 64.4 and 59.2% for
      backhand rotation at 60 and 120 degrees x s(-1), respectively. In females,
      slightly greater (P < 0.001) backhand rotation strength (right rotation in a
      right-handed player) was measured at both testing speeds with peak torque to body
      weight ratios ranging between 47.7 and 45.1% for left rotation and 50.8 and 48.3%
      for right rotation at 60 and 120 degrees x s(-1), respectively. Left
      rotation/right rotation ratios ranged from 95 to 98% for males and from 94 to 96%
      for females. CONCLUSIONS: Elite-level male tennis players have symmetric trunk
      rotation strength. Elite female tennis players have slightly greater backhand
      rotation strength (by 4-8%) than forehand rotation. Conditioning programs for
      elite tennis players should include exercises to facilitate and develop bilateral
      trunk rotation.

PMID- 15514514
TI  - Heart rate monitoring as a measure of physical activity in children.
AB  - PURPOSE: Using a larger sample and broader range of activities than most previous
      investigations of HR monitoring, this study examined the need for individual
      calibration of the HR-VO2 prediction equation, the effect of including low
      intensity activities when establishing the HR-VO2 equation, comparisons of
      different methods for calculating HR-VO2 prediction equations for maximum energy
      expenditure (EE) variance, and the effect of these different methods when applied
      to free-living HR data. METHODS: Forty-three children ages 8 to 12 completed
      laboratory assessments of the relationship between HR and VO2. Different methods
      of estimating daily EE were applied to free-living HR data collected from 37 of
      these children. RESULTS: There was significant individual variation in the HR-VO2
      prediction equations. HR monitoring predicted VO2 during low-intensity
      activities, below most established cut points. Individual differences persisted
      during both high- and low-intensity activities. Although a HR-VO2 prediction
      equation generated from the group accounted for 85% of the variance in EE,
      significant improvements in prediction were achieved with individualized HR-VO2
      prediction equations that took into account low-intensity activity levels.
      CONCLUSION: Generic equations derived from group data may be suitable for some
      applications. However, for investigators requiring more precision, individual HR
      VO2 equations significantly improve prediction.

PMID- 15514515
TI  - Reliability and variability of running economy in elite distance runners.
AB  - PURPOSE: To establish the typical error (TE) associated with equipment, testing,
      and biological variation of a running economy (RE) test in 11 elite male distance
      runners (VO2max 70.3 +/- 7.3 mL x min(-1) x kg(-1)), and measure the between
      athlete variation of 70 highly trained runners (VO2max 69.7 +/- 6.0 mL x min(-1)
      x kg(-1)) to determine the magnitude of the smallest worthwhile change (SWC)
      required for RE. METHODS: Runners performed three 4-min bouts of submaximal
      treadmill running at speeds of 14, 16, and 18 km x h(-1) (0% grade), on two
      separate occasions within a 7-d period to determine reliability and once over a 3
      yr period to measure the SWC. During all RE tests O2 consumption (VO2),
      ventilation (VE), respiratory exchange ratio (RER), heart rate (HR), stride rate
      (SR), and concentration of blood lactate (Lac) were determined. RESULTS: The TE
      for the pooled data of three running speeds (14, 16, and 18 km x h(-1)) was 2.4%
      for VO2, 7.3% for VE, 27% for Lac, and ranged between 1 and 4% for RER, HR, and
      SR. CONCLUSIONS: The results demonstrate that although the magnitude of the TE
      for a submaximal treadmill running protocol of three 4-min work efforts is small
      (2.4-7.3%) for measures associated with cardiorespiratory parameters, it is three
      to fourfold higher for Lac. Given the small TE associated with RE, and a SWC of
      similar magnitude for this cohort of distance runners, the RE test is useful in
      detecting changes attributable to training interventions. Changes in RE greater
      than approximately 2.4% in this cohort of elite distance runners are likely to be
      "real" and "worthwhile," and not simply related to testing error and typical
      variation.

PMID- 15514516
TI  - Elbow flexion and extension strength relative to body or muscle size in children.
AB  - PURPOSE: The purpose of this study was to examine gender- and age-related
      differences in elbow flexion and extension strength in children, when linear size
      measurements and actual measurements of muscle size were used as explanatory
      variables in a multilevel model. METHODS: Thirty-seven children participated in a
      3-yr longitudinal study (18 boys and 19 girls). The average age +/- SD at the
      first test occasion was 13.0 +/- 0.3 yr. Stature, arm length, isokinetic
      concentric and isometric elbow extension and flexion torques, and MRI-determined
      elbow flexor and extensor muscle cross-sectional areas (CSAs) were assessed
      annually. Multilevel modeling was used to describe the relationship between the
      measured torques and body/muscle size variables, incorporating age, age by
      gender, and gender as additional explanatory variables. RESULTS: When muscle CSA
      was included in the static and dynamic torque multilevel models, gender
      differences in strength were nonsignificant. In contrast, use of stature or arm
      length alone, suggested gender differences in strength that could not be
      explained by differences in body size. All torque measures were best explained by
      inclusion of muscle CSA and a linear dimension in the models. Age also explained
      additional variance in torque, but the influence of age was action and muscle
      specific. CONCLUSION: Use of only linear dimensions rather than muscle CSA to
      account for differences in size may have clouded our understanding of strength
      development in children.

PMID- 15514517
TI  - American College of Sports Medicine Position Stand: physical activity and bone
      health.

PMID- 15514518
TI  - Physical activity programs and behavior counseling in older adult populations.
AB  - Physical activity offers one of the greatest opportunities for people to extend
      years of active independent life and reduce functional limitations. The purpose
      of this paper is to identify key practices for promoting physical activity in
      older adults, with a focus on older adults with chronic disease or low fitness
      and those with low levels of physical activity. Key practices identified in
      promotion activity in older adults include: 1) A multidimensional activity
      program that includes endurance, strength, balance, and flexibility training is
      optimal for health and functional benefits; 2) Principles of behavior change,
      including: social support, self-efficacy, active choices, health contracts,
      assurances of safety, and positive reinforcement enhance adherence; 3) Management
      of risk by beginning at low intensity but gradually increasing to moderate
      physical activity, which has a better risk-to-benefit ratio and should be the
      goal for older adults; 4) An emergency procedure plan is prudent for community
      based programs; and 5) Monitoring aerobic intensity is important for progression
      and for motivation. Selected content review of physical activity programming from
      major organizations and institutions are provided. Regular participation in
      physical activity is one of the most effective ways for older adults, including
      those with disabilities, to help prevent chronic disease, promote independence,
      and increase quality of life in old age.

PMID- 15514519
TI  - Mass participation event management for the team physician: a consensus
      statement.

PMID- 15514520
TI  - Decompressive laparotomy to treat intractable intracranial hypertension after
      traumatic brain injury.
AB  - INTRODUCTION: Increases in intra-abdominal pressure (IAP) can cause increases in
      intracranial pressure (ICP). Recently, we noticed that abdominal fascial release
      could be useful in treating intracranial hypertension (ICH) after traumatic brain
      injury (TBI). We added this as an option in our treatment of TBI. METHODS: In our
      institution, ICH is treated with an algorithm using osmolar therapy, CSF drainage
      and barbiturates. Patients with refractory ICH have routine measurement of IAP.
      If elevated, consideration is given to decompressive laparotomy. We
      retrospectively reviewed all patients admitted from January 2000 through July
      2003 who had abdominal decompression to treat refractory ICH. RESULTS: From 1/00
      to 7/03, 17 patients underwent decompressive laparotomy for intractable ICH.
      Thirteen male and 4 females all sustained blunt injury. All had failed maximal
      therapy including 14 who had had decompressive craniectomy. Mean ICP was 30 +/-
      8.1 mmHg (range 20-40 mmHg) before decompression. No patients had evidence of
      abdominal compartment syndrome (ACS). Before decompression mean IAP was 27.5 (+/-
      5.2) mmHg (range 21-35 mmHg). After abdominal decompression ICP dropped
      precipitously by at least 10 mmHg to a mean of 17.5 (+/- 3.2) mmHg (range 10-25
      mmHg). In 6 patients the decrease in ICP was transient. All died. The remaining
      11 had sustained decreases in ICP. All survived, made neurologic recovery and
      were discharged to a rehabilitation facility. CONCLUSION: Decompressive
      laparotomy can be a useful adjunct in the treatment of ICH failing maximal
      therapy following TBI. More work will need to be done to precise the exact
      indications for this therapy.

PMID- 15514521
TI  - Ten year experience of burn, trauma, and combined burn/trauma injuries comparing
      outcomes.
AB  - BACKGROUND: Percent total body surface area (TBSA) burn, inhalation injury (INH),
      and age all have been shown to be independent predictors of mortality in burn
      victims. Little is known regarding patients sustaining combined thermal and
      mechanical injuries in relation to either injury sustained in isolation or with
      regard to these variables. This descriptive study profiles the 10-year experience
      of a single American Burn Association/American College of Surgeons verified Level
      I trauma and burn center and the treatment of this patient population. METHODS: A
      retrospective review of all burn and trauma patients admitted between 1990 and
      2000. Patients were divided into three groups; Burn only (B), Trauma only (T),
      and combined Burn/Trauma (B/T). Groups were compared with respect to age, TBSA
      burn, length of stay (LOS), Injury Severity Score (ISS), INH and mortality. These
      groups were then compared with B, T and B/T patients from the National Burn
      Repository (NBR) and National Trauma Data Bank (NTDB). Student's t test and chi
      tests were performed, as well as multiple logistic regression to identify
      independent predictors of mortality. p <0.05 was considered significant. RESULTS:
      Through our trauma registry, 24,093 patients were identified (T=22,284, B=1717
      and B/T=92). When comparing B and T, there was no difference in age, LOS, ISS, or
      mortality to those patients in the NBR or NTDB. B/T patients showed significantly
      increased percentage with INH (B/T=44.5% versus 11%), increased LOS (B/T=18 days
      versus 13.7 B and 5.3 T) and increased mortality (B/T=28.3% versus 9.8% B and
      4.3% T). B/T were also significantly older (B/T=40.1 years versus 31.0 B and 35.1
      T). When these variables are compared with the NBR and the NTDB benchmarks,
      mortality (28.3% versus 11.6% NBR and 7.0% NTDB) and ISS (23 versus 11.7 NTDB)
      were significantly higher with no difference in age (40.1 versus 33.4 NTDB, 35.9
      NBR), LOS (18 days versus 23.3 NBR) or TBSA (20.8% versus 19.5% NBR). Multiple
      logistic regression comparing TBSA, age, ISS and INH of survivors versus non
      survivors identified only ISS as an independent predictor of mortality.
      CONCLUSION: B combined with T presents a rare injury pattern that has a
      synergistic effect on mortality. Physicians and caregivers should be aware of a 2
      3 fold increase in the incidence of INH in this population, and increased
      mortality despite similar TBSA burned when compared with patients with B as the
      sole mechanism; ISS appears to be an independent predictor of mortality in this
      combined injury pattern.

PMID- 15514522
TI  - Blood transfusion is associated with donor leukocyte microchimerism in trauma
      patients.
AB  - INTRODUCTION: Blood transfusion can result in survival of donor leukocyte
      subpopulations in the recipient. Persistence of donor leukocytes in the
      transfusion recipient is termed microchimerism. Microchimerism likely reflects
      engraftment of the recipient with donor hematopoietic stem cells and is very
      uncommon with transfusion for elective surgery, sickle cell anemia, thalassemia,
      and HIV. We have found, however, that microchimerism may be more common in trauma
      patients. OBJECTIVE: To determine how frequently transfusion after trauma is
      associated with microchimerism. METHODS: We prospectively enrolled 45 trauma
      patients who were transfused > or =2 units of PRBCs. We sampled blood before
      hospital discharge and determined microchimerism by polymerase chain reaction
      (PCR) analysis of specimens using quantitative allele-specific HLA DR assays to
      detect non-recipient alleles. Data are expressed as median with interquartile
      range. RESULTS: Patients had a median age of 38 (interquartile range 25, 58)
      years, ISS of 19 (13, 29), and mortality of 7%. Seventy-eight percent were men,
      and 84% had blunt trauma. Patients received a median of 6 (4, 16) (range 2, 87)
      units of PRBCs. Of the 45 patients, 24 (53%) had evidence of microchimerism.
      Compared with patients without evidence of microchimerism, these patients had no
      difference in mean age, gender, ISS, units of PRBCs transfused, time from
      transfusion to blood sampling, or proportion that underwent splenectomy. Twenty
      one of the 24 patients with microchimerism had only 1 or 2 non-recipient DR
      alleles identified by PCR. CONCLUSIONS: Transfusion after trauma is associated
      with over half of recipients having evidence of microchimerism. Age, sex, ISS,
      and splenectomy of the recipient and the number of transfused units did not
      correlate with microchimerism. Because the median time from transfusion to
      sampling for PCR analysis was not longer in the group without microchimerism, it
      is unlikely microchimerism is due merely to failure of the recipient to clear
      transfused donor leukocytes.

PMID- 15514523
TI  - Factor VIIa for correction of traumatic coagulopathy.
AB  - INTRODUCTION: Activated factor VIIa (FVIIa) was developed to treat hemophiliacs
      with high-titer antibodies to factor VIII. FVIIa initiates thrombin formation by
      binding with exposed tissue factor. Anecdotal reports have described the utility
      of FVIIa in correcting coagulopathy from trauma, but no large series exists. We
      present our experience with 81 coagulopathic trauma patients treated using FVIIa
      in years 2001-2003, compared with "control" patients matched from the trauma
      registry from the same time period. METHODS: Use of FVIIa was restricted to
      active hemorrhage with clinical coagulopathy. We recorded the cause of
      coagulopathy, dose of FVIIa administered, effect on clinical coagulation,
      pertinent laboratory values, length of stay, number and type of blood products
      administered, and patient outcome. For the same time period we also examined
      outcomes in coagulopathic patients who did not receive FVIIa. RESULTS: Causes of
      coagulopathy were diverse, and included acute traumatic hemorrhage (46 patients),
      traumatic brain injury (20), warfarin use (9), congenital Factor VII deficiency
      (2), and other acquired hematologic defects (4). Coagulopathy was reversed in
      61/81 cases (75%), with an associated reduction in PT from 19.6 to 10.8
      (p=0.000018). 34 patients (42%) survived to hospital discharge (20/46 traumatic
      hemorrhage, 5/20 TBI, 4/9 on warfarin, 2/2 factor deficient, 3/4 other). Patients
      died from irreversible shock, multiple organ system failure, or traumatic brain
      injury. FVIIa patients had a higher mortality than coagulopathic controls matched
      by specific anatomic injuries, admission lactate value, and predicted probability
      of survival. Only a group identified by all three characteristics had a similar
      mortality to the FVIIa cohort, but the number of patients that could be matched
      this way was too small to be meaningful. CONCLUSION: FVIIa therapy lead to an
      immediate reduction in coagulopathic hemorrhage in most cases, accompanied by a
      significant improvement in laboratory measures. Application of FVIIa as a therapy
      of last resort makes the identification of equivalent control patients difficult.
      Use of FVIIa should be considered for any patient with coagulopathic hemorrhage
      in which surgically-accessible bleeding has been controlled. Prospective trials
      of FVIIa in patients with traumatic coagulopathy are strongly indicated, and
      should focus on appropriate patient selection and the dose and timing of therapy.

PMID- 15514524
TI  - Transfusion-induced leukocyte IL-8 gene expression is avoided by the use of human
      polymerized hemoglobin.
AB  - BACKGROUND: Red blood cell (pRBC) transfusion is an independent risk factor for
      multiple organ failure (MOF); a maladaptive immuno-inflammatory response is
      implicated. Interleukin-8 (IL-8) is one putative mediator of this response. We
      previously observed that injured patients resuscitated with pRBCs have increased
      plasma IL-8 compared with those given human polymerized hemoglobin (PolyHb). To
      further elucidate the mechanisms responsible for this difference in IL-8, we
      devised an ex-vivo transfusion model. We hypothesize that pRBC transfusion
      induces increased IL-8 gene expression that is avoided by the use of PolyHb.
      METHODS: Human volunteer blood was incubated alone (RB) or with a major
      transfusion (50% exchange) of either post-storage leukoreduced O-pRBCs (RB +
      pRBC) or PolyHb (RB + PolyHb) for 30 minutes at 37 degrees C. Total leukocyte
      (TL) or polymorphonuclear leukocyte (PMN) total RNA was isolated and IL-8 mRNA
      quantified. Results are reported as amol IL-8 mRNA/microg total RNA +/- SEM.
      Stats: ANOVA with Bonferroni/Dunn post hoc analysis. RESULTS: Simulated
      transfusion of pRBCs increased TL IL-8 mRNA (RB=0.28 +/- 0.10 amol/microg total
      RNA, RB + pRBC=2.24 +/- 0.25 amol/microg total RNA, p <0.01), whereas PolyHb did
      not (B + PolyHb=0.82 +/- 0.30 amol/microg total RNA). PolyHb IL-8 mRNA was less
      than pRBC transfused (p <0.01). In PMNs, simulated transfusion of pRBCs increase
      IL-8 mRNA (RB=3.17 +/- 1.05 amol/microg total RNA, RB + pRBC=7.60 +/- 1.79
      amol/microg total RNA, p <0.01), whereas PolyHb did not (RB + PolyHb=4.53 +/-
      1.64 amol/microg total RNA). CONCLUSIONS: Stored pRBCs induces increased TL and
      PMN IL-8 gene expression, whereas human polymerized hemoglobin, in lieu or pRBCs,
      avoids this increase. These experimental results corroborate our previous
      clinical studies and further encourage the study of PolyHb as a resuscitation
      strategy to decrease postinjury MOF.

PMID- 15514525
TI  - A hemoglobin based oxygen carrier, bovine polymerized hemoglobin (HBOC-201)
      versus Hetastarch (HEX) in an uncontrolled liver injury hemorrhagic shock swine
      model with delayed evacuation.
AB  - BACKGROUND: As HBOC-201 improves outcome in animals with hemorrhagic shock (HS),
      we compared HBOC-201 and HEX (used by U.S. military special operations forces) in
      a swine model of delayed evacuation and uncontrolled HS. METHODS: Twenty-four
      Yucatan pigs underwent a grade III liver injury and were resuscitated with HBOC
      201, HEX, or no fluid (NON). Additional infusions were given for hypotension or
      tachycardia. After 4 hours, the liver was repaired; IV fluids and blood
      transfusions were administered. Pigs were monitored for 72 hours. RESULTS:
      Survival was 7/8, 1/8, and 1/8 in HBOC-201-, HEX-, and NON-resuscitated pigs,
      respectively. Compared with HEX, HBOC-201 pigs had higher systemic and pulmonary
      artery pressures and had comparable cardiac outputs, but were less tachycardic.
      Transcutaneous tissue oxygenation was restored more rapidly in HBOC-201 pigs,
      there was a trend to lower lactic acid, and base deficit was less. HBOC-201 pigs
      had lower fluid requirements, higher urine output, and lower blood loss than HEX
      pigs. CONCLUSIONS: Despite evidence of vasoactivity, HBOC-201 more effectively
      stabilized tissue oxygenation, reversed anaerobic metabolism, decreased bleeding,
      and increased survival in comparison with HEX. If confirmed in clinical trials,
      these data suggest that for the resuscitation of combat casualties with delayed
      evacuation and uncontrolled HS due to solid organ injury, HBOC-201 is a superior
      low-volume resuscitative fluid.

PMID- 15514526
TI  - Screening for abdominal injury prior to emergent extra-abdominal trauma surgery:
      a prospective study.
AB  - OBJECTIVE: To prospectively evaluate the necessity of abdominal screening with
      computed tomography (CT) in awake and alert blunt trauma patients that require
      emergent extra-abdominal trauma surgery. METHODS: All blunt trauma patients
      admitted to a Level I trauma center that required emergent extra-abdominal trauma
      surgery were entered in a prospective study during the period from April 2001 to
      June 2003. Awake and alert blunt trauma patients (Glasgow Coma Scale [GCS] score
      > or =14) with a normal abdominal physical examination requiring extra-abdominal
      emergent surgery were entered in the study. All patients entered were greater
      than 14 years of age, hemodynamically stable, and underwent further abdominal
      evaluation with CT scan following the decision for extra-abdominal surgical
      intervention. Emergent extra-abdominal trauma surgery occurred within 8 hours of
      emergency room admission. The results of all diagnostic studies, hemodynamic
      values, mechanism of injury indications for extra-abdominal surgical intervention
      and outcome were analyzed. RESULTS: One hundred sixty-two patients were entered
      in the study with average age of 32 years (range: 14-81). The most common
      mechanism of injury was motor vehicle crash (76%). One hundred forty-three (88%)
      patients presented with GCS scores of 15, and 19 (12%) patients presented with
      GCS scores of 14. The majority of extra-abdominal emergent surgical procedures
      were orthopedic (88%). Two (1.2%) intra-peritoneal injuries were diagnosed in the
      study population. One of the injuries was a stable Grade 1 splenic injury and the
      other was a small bowel mesenteric hematoma. Neither of the 2 abdominal missed
      injury required blood transfusion or surgical intervention. CONCLUSIONS: Before
      emergent extra-abdominal trauma surgery, abdominal evaluation with physical
      examination is sufficient to identify surgically significant abdominal injury in
      the awake and alert blunt trauma patient. Abdominal screening with computed
      tomography does not impact patient outcome.

PMID- 15514527
TI  - Use of presumptive antibiotics following tube thoracostomy for traumatic
      hemopneumothorax in the prevention of empyema and pneumonia--a multi-center
      trial.
AB  - OBJECTIVE: To determine whether presumptive antibiotics reduce the risk of
      empyema or pneumonia following tube thoracostomy for traumatic hemopneumothorax.
      METHODS: A prospective, randomized, double-blind trial was performed comparing
      the use of cefazolin for duration of tube thoracostomy placement (Group A) versus
      24 hours (Group B) versus placebo (Group C). RESULTS: A total of 224 patients
      received 229 tube thoracostomies. Logistic regression analysis revealed that
      duration of tube placement and thoracic acute injury score were predictive of
      empyema (p <0.05). Empyema tended to occur more frequently in patients with
      penetrating injuries (p=0.09). chi analysis showed pneumonia occurred
      significantly more frequently in blunt than penetrating injuries (p <0.05).
      Presumptive antibiotic use did not significantly effect the incidence of empyema
      or pneumonia, although no empyemas occurred in Group A. CONCLUSIONS: The
      incidence of empyema was low and the use of presumptive antibiotics did not
      appear to reduce the risk of empyema or pneumonia.

PMID- 15514528
TI  - Urgent airways after trauma: who gets pneumonia?
AB  - BACKGROUND: Several risk factors, including emergent intubation, severe head
      injury, shock, blunt trauma, and high severity of injury, have been identified as
      risk factors for the development of pneumonia after trauma. This study assesses
      the contribution of emergent intubation to the development of pneumonia after
      injury. METHODS: A retrospective review of all trauma patients requiring
      intubation or cricothyroidotomy in the Emergency Department (ED) or in the pre
      hospital area (field) over a 41/2 year period. RESULTS: 571 patients comprised
      the study population. Of these, 80% had airways established in the ED, while 20%
      were intubated in the field. Field intubation was associated with a lower Glasgow
      Coma Scale (GCS) score (p <0.0001) and more severe injury (p <0.0001),
      particularly to the chest and extremities.Twenty-five percent of the population
      developed pneumonia. Patients diagnosed with pneumonia were older (p=0.009), and
      had a higher ISS (p <0.0001), lower GCS score, (p <0.008), longer ICU and
      hospital length of stay (p < 0.0001). Injuries to the head, thorax and
      extremities were more common (p < 0.05) and more severe (p <0.05) in patients
      developing pneumonia. The incidence of pneumonia after field airway was
      significantly higher (35% versus 23%, p=0.048).Multiple logistic regression
      analysis identified field intubation, age, AIS-head, and AIS-extremity as
      independent risk factors for pneumonia. CONCLUSION: Pre-hospital but not ED
      intubation is an independent risk factor for the development of post-traumatic
      pneumonia. Other predictors include the severity of injury, specifically head and
      extremity injuries.

PMID- 15514529
TI  - Modified rapid deployment hemostat bandage terminates bleeding in coagulopathic
      patients with severe visceral injuries.
AB  - BACKGROUND: We recently reported that a new dressing, the Modified Rapid
      Deployment Hemostat (MRDH) controlled bleeding in hypothermic coagulopathic swine
      after traumatic liver avulsion. The purpose of this study was to evaluate the
      MRDH in coagulopathic trauma patients undergoing abbreviated laparotomy. METHODS:
      A prospective, observational clinical trial of the MRDH dressing was performed at
      our Level One Trauma Center in patients with high-grade visceral injuries with
      coagulopathy who failed conventional therapy and required packing. Attending
      surgeons graded the injury and the adequacy of hemostasis following application
      of the dressing. Patients were followed until discharge or death. RESULTS: Ten
      patients were enrolled: nine severe hepatic injuries, and one major abdominal
      vascular injury. All patients were hypothermic, acidotic, and clinically
      coagulopathic. Intraoperative hemostasis was immediately obtained after MRDH
      placement in all cases except one. There was one death. CONCLUSION: The Modified
      Rapid Deployment Hemostat terminates bleeding from severe visceral injuries in
      coagulopathic patients undergoing abbreviated laparotomy.

PMID- 15514530
TI  - Change in velocity and energy dissipation on impact in motor vehicle crashes as a
      function of the direction of crash: key factors in the production of thoracic
      aortic injuries, their pattern of associated injuries and patient survival. A
      Crash Injury Research Engineering Network (CIREN) study.
AB  - OBJECTIVE: To examine the effect of change in velocity (MV) and energy
      dissipation (IE) on impact, above and below the test levels for federal motor
      vehicle crash (MVC) safety standards, on the incidence of aortic injury (AI) and
      its mortality and associated injury patterns in frontal (F) and lateral (L) MVCs.
      Comparison of 80 AI and 796 non-AI patients of AIS=3. METHODS: Eight hundred
      seventy-six MVC adult drivers or front-seat passengers (552 F and 324 L)
      evaluated by 10 Level I CIREN study Trauma Centers together with vehicle and
      crash scene engineering reconstruction. Patient seatbelt and/or airbag use
      correlated with clinical or autopsy findings. RESULTS: In AI, 63% of cases were
      dead at the scene and only 16% survived to leave hospital. The relation between
      IE dissipated in the MVC and the DeltaV on impact was exponential as DeltaV
      increased, but the rise in IE for a given DeltaV was greater in LMVC than in FMVC
      (p <0.05). A more rapid rise in IE/DeltaV occurred above the mean DeltaV of 48 +/
      19.7 kph (30 mph) in FMVC and above the mean DeltaV of 36 +/- 16.2 kph (23 mph)
      in LMVC. As DeltaV increased above these means, 65% of 46 FMVC aortic injuries
      (AIs) and 64% of 34 LMVC AIs occurred. In AI patients there was evidence of
      focusing of the point of IE impact on the upper chest with a higher incidence of
      rib1-4 fractures than in non-AI (p <0.01) and more brain, heart, lung and spleen
      injuries (p <0.01) consequent to lower seatbelt use (p <0.01), but LMVC also had
      more pelvic fx (p <0.05). Airbags + seatbelts in FMVC and seatbelts in LMVC
      reduced mortality (p <0.05) Comparison of AI incidence in three successive 4-year
      vehicle model year periods showed a progressive decrease as new safety devices
      were introduced (p < 0.05). CONCLUSIONS: The implications for AI of the focused
      IE at the upper chest suggest a probable mechanism for MVC AI with the
      pressurized aortic arch acting as the long arm of a lever system with the fulcrum
      at the subclavian artery, producing maximum torsional strain at the short arm of
      the isthmus where 75% of the AIs occurred. AI mortality is also influenced by the
      associated injuries. To develop more effective safety systems to prevent AI, MVC
      safety testing with airbags and seatbelts should be carried out at DeltaVs of 1
      SD above means for FMVC and LMVC.

PMID- 15514531
TI  - The new car assessment program: does it predict the relative safety of vehicles
      in actual crashes?
AB  - BACKGROUND: Federal motor vehicle safety standards are based on crash test dummy
      analyses that estimate the relative risk of traumatic brain injury (TBI) and
      severe thoracic injury (STI) by quantifying head (Head Injury Criterion [HIC])
      and chest (Chest Gravity Score [CGS]) acceleration. The New Car Assessment
      Program (NCAP) combines these probabilities to yield the vehicle's five-star
      rating. The validity of the NCAP system as it relates to an actual motor vehicle
      crash (MVC) remains undetermined. We therefore sought to determine whether HIC
      and CGS accurately predict TBI and STI in actual crashes, and compared the NCAP
      five-star rating system to the rates of TBI and/or STI in actual MVCs. METHODS:
      We analyzed frontal crashes with restrained drivers from the 1994 to 1998
      National Automotive Sampling System. The relationship of HIC and CGS to the
      probabilities of TBI and STI derived from crash tests were respectively compared
      with the HIC-TBI and CGS-STI risk relationships observed in actual crashes while
      controlling for covariates. Receiver operating characteristic curves determined
      the sensitivity and specificity of HIC and CGS as predictors of TBI and STI,
      respectively. Estimates of the likelihood of TBI and/or STI (in actual MVCs) were
      compared with the expected probabilities of TBI and STI (determined by crash test
      analysis), as they relate to NCAP ratings. RESULTS: The crash tests overestimate
      TBI likelihood at HIC scores >800 and underestimate it at scores <500. STI
      likelihood is overestimated when CGS exceeds 40 g. Receiver operating
      characteristic curves demonstrated poor sensitivity and specificity of HIC and
      CGS in predicting injury. The actual MVC injury probability estimates did not
      vary between vehicles of different NCAP rating. CONCLUSION: HIC and CGS are poor
      predictors of TBI and STI in actual MVCs. The NCAP five-star rating system is
      unable to differentiate vehicles of varying crashworthiness in actual MVCs. More
      sensitive parameters need to be developed and incorporated into vehicle crash
      safety testing to provide consumers and automotive manufacturers with useful
      tools with which to measure vehicle safety.

PMID- 15514532
TI  - Pediatric trauma in southwestern Ontario: linking data with injury prevention
      initiatives.
AB  - BACKGROUND: Our objective was to provide an epidemiologic description of
      pediatric trauma in SW Ontario using multiple data sets. Injury prevention (IP)
      initiatives were linked with predominant injury mechanisms to determine whether
      IP programs were supported by data. METHODS: Descriptive analysis was undertaken
      for five pediatric age groups (<1 year, 1-4 years, 5-9 years, 10-14 years, 15-19
      years) using the Ontario Trauma Registry's Death Data Set, Comprehensive Data Set
      (Lead Trauma Hospitals [LTH] patients), and Minimal Data Set (hospital
      admissions), 1999-2000, for all pediatric patients residing in SW Ontario.
      National Ambulatory Care Reporting System (NACRS) data from the Children's
      Hospital of Western Ontario/London Health Sciences Centre were used to capture
      the Emergency Room (ER) injury data. Information on IP initiatives for children
      and youth was gathered through an Internet search, supplemented by a survey.
      RESULTS: Injury in SW Ontario resulted in 13,197 ER visits, 1,616 hospital
      admissions, 70 severe trauma (ISS > 12) cases treated at a LTH and 47 deaths to
      children and youth. More males than females were injured, with the sex
      differential more pronounced as age increased. Falls were the leading mechanism
      for ER visits (37%) and hospital admissions (26%). Recreational injuries
      represented approximately 30% of injuries to the 10-14 yr age group. As ISS
      increased, MVCs emerged as an important mechanism, representing 71% of LTH cases
      and 53% of pediatric injury deaths in SW Ontario. There were 61 pediatric IP
      programs identified in SW Ontario. Eighty-four percent of programs (51/61) were
      supported by data, and were related to one of the predominant injury mechanisms.
      CONCLUSIONS: Injury is a serious problem for children in SW Ontario. Data can be
      used to identify modifiable risk factors to develop and implement new IP
      initiatives with the goal of reducing childhood injury and death. There is a need
      to integrate and link IP programs in SW Ontario for full coverage of all injury
      mechanisms.

PMID- 15514533
TI  - Predictors of patients who will develop prolonged occult hypoperfusion following
      blunt trauma.
AB  - BACKGROUND: Prolonged occult hypoperfusion or POH (serum lactate >2.4 mmol/L
      persisting >12 hours from admission) represents a reversible risk factor for
      adverse outcomes following traumatic injury. We hypothesized that patients at
      increased risk for POH could be identified at the time of admission. METHODS:
      Prospective data from adult trauma admissions between January 1, 1998 and
      December 31, 2000 were analyzed. Potential risk factors for POH were determined
      by univariate analysis (p < or =0.10= significant). Significant factors were
      tested in a logistic regression model (LR) (p < or =0.05= significant). The
      predictive ability of the LR was tested by receiver operating curve (ROC)
      analysis (p < or =0.05= significant). RESULTS: Three hundred seventy-eight
      patients were analyzed, 129 with POH. Injury Severity Score (ISS), emergency
      department Glasgow Coma Scale score, hypotension, and the individual Abbreviated
      Injury Scale score (AIS) for Head (H), Abdominal/Pelvic Viscera (A) and
      Pelvis/Bony Extremity (P) were significantly associated with POH. LR demonstrated
      that ISS, A-AIS > or =3 and P-AIS > or =3 were independent predictors of POH (p
      <0.05). ROC analysis of the LR equation was statistically significant (Area=0.69,
      p <0.001). CONCLUSIONS: We identified factors at admission that placed patients
      at higher risk for developing POH. Select patients may benefit from rapid,
      aggressive monitoring and resuscitation, possibly preventing POH and its
      associated morbidity and mortality.

PMID- 15514534
TI  - Cardiac troponin I as a predictor of arrhythmia and ventricular dysfunction in
      trauma patients with myocardial contusion.
AB  - BACKGROUND: Myocardial contusion during blunt chest trauma is common and may lead
      to potentially fatal cardiac complications. Therefore, it is useful to identify a
      serum marker reflecting the myocardial damage that can predict risk for cardiac
      complications. In this study, the authors determined the strength of the
      association between cardiac troponin I (cTnI) levels and the risk of arrhythmia
      or the development of left ventricular dysfunction in a cohort of patients with
      blunt chest trauma. METHODS AND RESULTS: In 187 multiply injured patients with
      blunt chest trauma, serial measurements of cTnI, total creatine kinase (CK), and
      isoenzyme of creatine kinase with muscle and brain subunits (CK-MB) were combined
      with sequential electrocardigraphic and echocardiographic recordings. The results
      showed that 63 patients (34%) had myocardial contusion, as defined by positive
      cTnI levels, of which 47 (25%) were symptomatic and 16 (9%) showed no
      abnormalities. The remaining 124 patients (66%) displaying negative CTnI levels
      were asymptomatic during the entire study. Severity of arrhythmia correlated
      directly with increase in cTnI levels. The levels of cTnI in the symptomatic
      group remained elevated significantly longer than the levels in the asymptomatic
      group. The depression of left ventricular ejection fraction was inversely
      correlated with the increase in cTn levels. The patients whose cTnI levels were
      below 1.05 microg/L at admission and during the first 6 hours afterward showed no
      cardiac abnormalities throughout the entire study period CONCLUSIONS: Levels of
      cTnI below 1.05 microg/L in asymptomatic patients at admission and within the
      first 6 hours after admission rule out myocardial injury, whereas positive cTn
      levels above 1.05 microg/L mandate further cardiologic workup for the detection
      and management of myocardial injury. Furthermore, the dynamics and peak levels of
      pathologic cTnI levels allow estimation of arrhythmia risk and left ventricular
      dysfunction in trauma patients with myocardial contusion.

PMID- 15514535
TI  - Open-chest cardiopulmonary resuscitation after cardiac arrest in cases of blunt
      chest or abdominal trauma: a consecutive series of 38 cases.
AB  - BACKGROUND: According to the literature, the overall outcome in a patient
      population with chest or abdominal injury with initial cardiac arrest has to be
      rated as poor. In cases of penetrating injuries, open-chest cardiopulmonary
      resuscitation (CPR) has been recommended as a treatment option to improve the
      survival rate. The aim of this study was to prove equal outcome for patients with
      blunt chest or abdominal trauma. METHODS: During a 5-year period, a consecutive
      patient series admitted to an urban Level I trauma center was examined. Only
      patients with blunt trauma and witnessed cardiac arrest, who had a documented,
      uninterrupted closed-chest CPR (CCCPR) of less than 20 minutes were included in
      this study (n=38). Exclusion criteria were age over 70 years, penetrating
      injuries, CCCPR of more than 20 minutes, as well as nonprofessional bystander
      resuscitation. RESULTS: Four of 38 patients survived. In comparison with the
      group of nonsurvivors, both groups showed a similar age and gender ratio (mean
      age, 28, 32, respectively). The mean Injury Severity Scale was 54 (range, 42-66)
      in the survivor group and 66 (range, 29-75) in the nonsurvivor group,
      respectively. The time of CCCPR was on average 13 minutes (range, 11-15 minutes)
      for the survivors and 16 minutes (range, 1-20 minutes) for the nonsurvivors.
      CONCLUSION: Patients with blunt trunk trauma and cardiac arrest after hemorrhagic
      shock may benefit from open-chest CPR with the same probability as shown for
      patients with penetrating injuries. This is especially true if the procedure is
      started as soon as possible, but at the latest within 20 minutes after initial
      CCCPR.

PMID- 15514536
TI  - Life-altering outcomes after lower extremity injury sustained in motor vehicle
      crashes.
AB  - BACKGROUND: Lower extremity injuries (LEIs) sustained in vehicular crashes result
      in physical problems and unexpected psychosocial consequences. Their significance
      is diminished by low Abbreviated Injury Scale scores. METHODS: Drivers who
      sustained LEIs were identified as part of the Crash Injury Research and
      Engineering Network (CIREN) and interviewed during hospitalization, at 6 months,
      and at 1 year. All were occupants of newer vehicles with seatbelts and airbags.
      RESULTS: Sixty-five patients were followed for 1 year. Injuries included mild
      brain injury (43%), ankle/foot fractures (55%), and bilateral injuries (37%). One
      year post-injury, 46% reported limitations in walking and 22% with ankle/foot
      fractures were unable to return to work. Depression (39%), cognitive problems
      (32%), and post-traumatic stress disorder (18%) were significant in the mild
      brain injury group. CONCLUSIONS: Long-lasting physical and psychological burdens
      may impede recovery and alter the lifestyle of patients with LEI. These issues
      need to be addressed by trauma center personnel.

PMID- 15514537
TI  - Bilateral lower leg replantation versus prosthetic replacement: long-term outcome
      of amputation after an occupational railroad accident.
AB  - BACKGROUND: This retrospective study investigated three very similar cases of
      bilateral lower leg amputation. The aim was to determine which of two
      therapeutical procedures is associated with better long-term outcome:
      replantation or primary treatment of the stumps and subsequent prosthetic
      replacement. METHODS: Evaluation included clinical examination, gait analysis,
      and a workup of the psychosocial background. Health problems were documented
      using the Nottingham Health Profile. Follow-up assessments were performed 6, 7,
      and 18 years after the trauma. RESULTS: One patient underwent successful
      bilateral lower leg replantation and continued to work for the same employer. Two
      patients underwent prosthetic replacement. One became a social outcast confined
      to a wheelchair. The other patient had a good psychosocial background, similar to
      that of the patient who underwent replantation. He showed a better gait analysis
      on even ground than the replantation patient, but the findings were vice versa
      for uneven ground. CONCLUSIONS: The decision between replantation and prosthetic
      replacement after bilateral lower leg amputation is case related and cannot be
      generalized. Patients who have undergone these procedures require long-term
      psychological and physiotherapeutic care to achieve a good long-term surgical
      outcome.

PMID- 15514538
TI  - The use of a locked plate in the treatment of ununited femoral shaft fractures.
AB  - BACKGROUND: Sixteen patients with ununited fractures of the femur were treated by
      locked plate. There were 14 men and 2 women. The youngest patient was 18 years
      old and the oldest was 48 years (average, 32.9 years). Two fractures were
      infected and 14 were noninfected. METHODS: Time between injury and operation
      varied from 4 to 26 months (average, 8.2 months). A standard broad dynamic
      compression plate and AO washers and nuts were used to construct a locked plate.
      Follow-up ranged from 6 to 24 months. RESULTS: All fractures have healed after
      this operation; bone graft was not used in any of them. Time until healing ranged
      from 4 to 6 months (average, 4.9 months). Shortening after surgery ranged from 0
      to 5 cm (average, 1.8 cm). There was no metal failure or recurrence of infection.
      Two patients were readmitted 1 year after operation for metal removal, knee
      arthrolysis, and quadricepsplasty to improve the range of motion of the knee.
      CONCLUSION: Locked plate fixation is rigid enough for bone healing and to allow
      early postoperative mobilization, with good functional outcome.

PMID- 15514539
TI  - The sternal fracture: radiographic analysis of 200 fractures with special
      reference to concomitant injuries.
AB  - BACKGROUND: The assessment of the sternal fracture and concomitant injuries is
      discussed. METHODS: Two hundred sternal fractures were analyzed with respect to
      accident circumstances, fracture morphology and topography, and associated
      injuries. RESULTS: Traffic accidents were frequent; 89.2% of them were motor
      vehicle crashes of restrained passengers, 76.5% of fractures were localized in
      the corpus sterni, and 8.5% of the injuries resulted in fractures or complete
      disruptions of the synchondrosis manubriosternalis. Nondisplaced or slightly
      displaced fractures (75.5%) occurred more frequently compared with moderately and
      severely displaced fractures (24.5%). In 29.5% of the patients, concomitant
      thoracic injuries were diagnosed. Spinal fractures were evaluated in 13%. In
      displaced fractures of the corpus, thoracic and cardiac injuries were observed
      frequently. In fractures or disruptions of the synchondrosis manubriosternalis,
      concurrence of spinal fractures clearly increased. CONCLUSION: The observation of
      fracture morphology and topography, with reference to displacement, gives
      important information about the existence of serious concomitant injuries and can
      determine further diagnostic and therapeutic options in sternal fractures.

PMID- 15514540
TI  - Can external fixation maintain reduction after distal radius fractures?
AB  - BACKGROUND: The purpose of this study was to assess the effectiveness of external
      fixation and percutaneous pinning in maintaining distal radius fracture reduction
      over a 6-month period and to identify factors that might predict loss of fracture
      reduction. METHODS: Seventy cases had complete radiographic evaluation before
      surgery; at surgery; and at 6-week, 3-month, and 6-month follow-up. Radiographic
      parameters measured included volar tilt, dorsal displacement, radial inclination,
      radial height, radial shift, and ulnar variance. RESULTS: Dorsal tilt averaged
      17.5 degrees from neutral before surgery; this value was corrected to 0.9 degree
      at surgery, but then progressed to 4.2 degrees by the 6-month follow-up. At 6
      month follow-up, 49% of cases had lost more than 5 degrees of initially reduced
      volar tilt. However, none of these patients went from an acceptable initial
      reduction to an unacceptable reduction at 6 months. Initial deformity, patient
      age, use of bone graft, and duration of external fixation were not predictors of
      loss of reduction. CONCLUSION: Loss of reduction of volar tilt was seen for a
      period of up to 6 months after fixation, despite the use of pinning to hold the
      reduction. No specific predictor of loss of reduction was noted, although there
      was a trend toward loss of reduction in younger patients.

PMID- 15514541
TI  - Investigation of computed tomographic scan concurrent criterion validity in
      doubtful scaphoid fracture of the wrist.
AB  - BACKGROUND: Rapid diagnosis of scaphoid bone fracture in the wrist is important
      so that appropriate treatment can be started. If a fracture is clinically
      suspected without being visible on radiography, further investigation has to be
      conducted to reveal a fracture or to rule it out. The objective of this study was
      to investigate the validity of computed tomographic (CT) scanning and bone
      scintigraphy compared with the clinical fracture rate during follow-up of 1 year
      for examining patients with a suspected scaphoid fracture. METHODS: Bone
      scintigraphy and CT scanning were performed in 29 patients with persistent
      clinical suspicion of a scaphoid bone fracture 5 to 10 days after trauma.
      RESULTS: The sensitivity, specificity, and positive and negative predictive
      values of the CT scan were 100%. The sensitivity, specificity, and positive and
      negative predictive values of bone scintigraphy were 78%, 90%, 78%, and 90%,
      respectively. Seven patients showed a fracture on both CT scanning and bone
      scintigraphy. Eighteen patients showed no fracture on both CT scanning and bone
      scintigraphy. A false-positive bone scintigram showed up in two patients and a
      false-negative bone scintigram in another two patients. CONCLUSION: CT scanning
      is a rapid, simple, valid method for demonstrating or ruling out a scaphoid
      fracture and is superior to bone scintigraphy.

PMID- 15514542
TI  - Tracheostomy after anterior cervical spine fixation.
AB  - BACKGROUND: Patients with cervical spine injury may require both anterior
      cervical spine fusion and tracheostomy, particularly in the setting of associated
      cervical spinal cord injury (SCI). Despite the close proximity of the two
      surgical incisions, we postulated that tracheostomy could be safely performed
      after anterior spine fixation. In addition, we postulated that the severity of
      motor deficits in patients with cervical spine injury would correlate with the
      need for tracheostomy. METHODS: A retrospective review was undertaken of all
      adult trauma patients diagnosed with cervical spine fractures or cervical SCI
      admitted between June 1996 and June 2001 at our university Level I trauma center.
      Demographic data, severity of neurologic injury based on the classification of
      the American Spinal Injury Association (ASIA), complications, and use and type of
      tracheostomy were collected. In the subgroup of patients with unstable cervical
      spine injury that underwent anterior stabilization and tracheostomy, data
      regarding timing and technique of these procedures and wound outcomes were also
      collected. Categorical data were analyzed using chi analysis using Yates
      correction when appropriate, with p <0.05 considered significant. RESULTS: During
      this time period, 275 adult survivors were diagnosed with cervical spinal cord or
      bony injury. Forty-five percent of patients with SCI (27 of 60) and 14% of
      patients without SCI (30 of 215) underwent tracheostomy (p <0.001). Moreover, on
      the basis of the ASIA classification system, 76% of ASIA A and B patients, 38% of
      ASIA C patients, 23% of ASIA D patients, and 14% of ASIA E patients were treated
      with tracheostomy (p <0.001). In the subgroup that underwent both anterior spine
      fixation and tracheostomy (n=17), the median time interval from spine fixation to
      airway placement was 7 days (interquartile range, 6-10 days), with 71% of these
      tracheostomies performed percutaneously. No patient developed a wound infection
      or nonunion as a consequence of tracheostomy placement, and there were no deaths
      because of complications of either procedure. CONCLUSION: These data support the
      safety of tracheostomy insertion 6 to 10 days after anterior cervical spine
      fixation, particularly in the presence of cervical SCI. The presence of severe
      motor neurologic deficits was strongly associated with the use of tracheostomy in
      patients with cervical spine injury. Percutaneous tracheostomy, which is our
      technique of choice, may be advantageous in this setting by virtue of creating
      only a small wound. The optimal timing and use of tracheostomy in patients with
      cervical spine injury requires further study.

PMID- 15514543
TI  - Tracheostomy in thermally injured patients: does diagnosis-related group 483
      adequately estimate resource use and hospital costs?
AB  - BACKGROUND: This study compares burn and nonburn patients undergoing
      tracheostomy, all of whom were assigned to diagnosis-related group 483 to
      determine hospital reimbursement. METHODS: We reviewed the records of all
      inpatients admitted to our hospital from January 2000 through December 2001 who
      underwent tracheostomy and who were assigned to diagnosis-related group 483. In
      addition, we compared our burn patient data with that from three other burn
      centers and the National Burn Repository. RESULTS: We identified 357 inpatients
      who had tracheostomies during their hospitalization, only 12 of whom (3.4%) had
      acute burn injuries. The mean extent of burn in these patients was 43.4% total
      body surface area. The most frequent primary diagnoses for nonburn patients were
      injury and poisoning, and circulatory and respiratory disorders. Patients with
      burn injuries had 39.6 ventilator days, 40.7 intensive care unit days, and 49.2
      hospital days compared with 19.8, 17.4, and 29.5 days, respectively, for nonburn
      patients (p <0.0001). Demographic, resource, and financial data for burn patients
      treated at the three other burn centers and those reported to the National Burn
      Repository were not significantly different from burn patients treated at our
      hospital. Total costs and charges for the care of burn patients were $186,830 and
      $343,904, respectively, compared with $82,176 and $160,498 for the nonburn
      patients (p <0.0005). CONCLUSION: Burn patients requiring tracheostomies during
      their acute hospitalization consume significantly more resources than patients
      without burn injuries. More appropriate resource-based reimbursement for the care
      of these patients appears warranted.

PMID- 15514544
TI  - Reduced hepatic expression of glutathione s-transferases in burned mice.
AB  - BACKGROUND: Glutathione S-transferases (GSTs) contribute to liver homeostasis and
      are released into plasma after liver injury. This study investigates the hepatic
      expression of key GST enzyme subtypes after burn injury. METHODS: Mice were
      subjected to an 18% total body surface area burn. Expression of mGSTalpha3 and
      mGSTmu1 was analyzed by reverse-transcriptase polymerase chain reaction and
      Western blots on liver preparations from burned and control mice. GST catalytic
      activity was measured by conjugation assays. RESULTS: : In burned animals,
      mGSTalpha3 mRNA was only reduced at 1 day, whereas mGSTmu1 mRNA decreased at 1
      day and at 3 days after injury. Total mGSTmu protein levels decreased at the same
      time points, whereas total mGSTalpha protein levels did not change. Also, by 3
      days, total GST conjugation activity was reduced by 25% (p=0.05). CONCLUSION:
      Reduced expression of specific alpha and mu GST enzymes after burns correlates
      functionally with reduced GST activity. Altered GST expression may contribute to
      liver damage after systemic injury.

PMID- 15514545
TI  - Trauma recidivism in a large urban canadian population.
AB  - BACKGROUND: Prevention of trauma might be achieved by risk factor modification.
      Identification of such risk factors can be pursued by various means. Trauma
      recidivists may possess and highlight risk factors. Accordingly, trauma
      recidivists were analyzed as a method to elucidate trauma risk factors. METHODS:
      A retrospective analysis of 13,057 trauma patients in Toronto was conducted.
      Forty-two recidivists were identified, and their first admission was compared
      with a control group of 84 non-recidivists. RESULTS: The rate of trauma
      recidivism was 0.38% overall. Trauma recidivists were more likely to be from the
      inner city, male, homeless, suffering from chronic medical conditions. In
      addition, psychiatric conditions, an alcoholism history or any alcohol at the
      time of injury, intentionally injured, or engaged in criminal activity were also
      significantly more common in recidivists (p <0.05). CONCLUSION: Risk factors for
      major trauma can be identified by analyzing recidivists in a large urban Canadian
      population.

PMID- 15514546
TI  - Large animal-related abdominal injuries.
AB  - BACKGROUND: This study investigated injuries to the abdominal area of the body
      caused by large animals, as well as the management of this problem. METHODS: All
      the patients with large animal-related abdominal injuries over a 10-year period
      were identified retrospectively through the general surgery registrations.
      RESULTS: Overall, 113 patients were hospitalized after large animal encounters
      during the 10-year study period, 33 (30%) of which had large animal-related
      abdominal injuries. These patients comprised 10 women (30%) and 23 men (70%) with
      a mean age of 56 +/- 14 years. Of the 33 patients, 31 (93.9%) sustained blunt
      injuries and 2 (6.1%) experienced penetrating abdominal trauma. The mean Injury
      Severity Score was 12.7 +/- 4.0, and the mean Acute Physiology and Chronic Health
      Evaluation II (APACHE II) score was 10.6 +/- 3.2. The mean intensive care unit
      stay was 0.8 +/- 2.2 days, and the total hospital length of stay was 7.3 +/- 5.6
      days. Whereas 12 patients (36.4%) were managed nonoperatively, 21 patients
      (63.6%) required surgery. Laparotomy showed injuries to the jejunum in three
      patients (9.1%), to the ileum in 13 patients (39.4%), to the ileal mesenterium in
      1 patient (3%), to the liver in 4 patients (12.1%), and to the spleen in 2
      patients (6.1%). One patient died of myocardial infarction on the second day
      after admission. CONCLUSIONS: Large animal-related injuries to the abdominal area
      can be serious. Immediate transportation and early diagnosis of abdominal insults
      are important because of the frequencies of small bowel and mesenteric injuries,
      which are difficult to diagnose using currently available diagnostic tools.

PMID- 15514547
TI  - Pregnancy is not a useful tissue expander in patients with an open abdomen: a
      case report.

PMID- 15514548
TI  - The liver bag: report of a new technique for treating severe, exsanguinating
      hepatic injuries.

PMID- 15514549
TI  - Feasibility of laparoscopic splenectomy in stable blunt trauma: a case series.

PMID- 15514550
TI  - Right ventricular air embolism during radiographic evaluation of a pediatric
      patient for blunt vehicular trauma.

PMID- 15514551
TI  - Floating thrombus of the thoracic aorta: a rare consequence of blunt trauma.

PMID- 15514552
TI  - Recalcitrant soft tissue pin-tract infection: a delayed complication of pediatric
      femoral shaft fracture treated with external fixator.

PMID- 15514553
TI  - Clinical practice guideline: endpoints of resuscitation.

PMID- 15514554
TI  - Exclusion and bypass--a new approach to popliteal artery injuries.

PMID- 15514555
TI  - Non-ventilatory-based strategies in the management of acute respiratory distress
      syndrome.

PMID- 15514556
TI  - Hyperacute head injuries and the timing of computed tomography.

PMID- 15514557
TI  - Tension pneumothorax, achilles, and the turtle.

PMID- 15514559
TI  - Studies in otitis media: Children's Hospital of Pittsburgh-University of
      Pittsburgh progress report--2004.
AB  - OBJECTIVES/HYPOTHESIS: The present Progress Report has summarized the key otitis
      media clinical trials and laboratory studies conducted since 1969 by
      investigators at the Children's Hospital of Pittsburgh-University of Pittsburgh
      (Pittsburgh, PA). STUDY DESIGN: Review. METHODS: Included in the discussion are
      the following: 1) studies of the epidemiology and risk factors; 2) anatomy and
      pathology of the eustachian tube-middle ear from human temporal bone
      histopathological specimens; 3) physiology and pathophysiology of the eustachian
      tube-middle ear in humans and animal models; 4) pathogenesis; 5) otitis media in
      special populations (e.g., patients with cleft palate, Native Americans, patients
      with Down syndrome); 6) microbiology; 7) diagnosis; 8) outcomes of randomized
      clinical trials that evaluated efficacy of nonsurgical and surgical methods of
      treatment and prevention; 9) studies of certain complications and sequelae (e.g.,
      effect of middle-ear effusion on hearing, early child development, and the
      vestibular system; chronic suppurative otitis media). Also included are relevant
      summary tables and 256 references.

PMID- 15514560
TI  - Recurrent respiratory papillomatosis: a longitudinal study comparing severity
      associated with human papilloma viral types 6 and 11 and other risk factors in a
      large pediatric population.
AB  - OBJECTIVES/HYPOTHESIS: A database was developed for prospective, longitudinal
      study of recurrent respiratory papillomatosis (RRP) in a large population of
      pediatric patients. Data recorded for each patient included epidemiological
      factors, human papilloma virus (HPV) type, clinical course, staged severity of
      disease at each surgical intervention, and frequency of surgical intervention.
      The study hypothesizes that patients with HPV type 11 (HPV-11) and patients
      younger than 3 years of age at diagnosis are at risk for more aggressive and
      extensive disease. STUDY DESIGN: The 10-year prospective epidemiological study
      used disease staging for each patient with an original scoring system. Severity
      scores were updated at each surgical procedure. METHODS: Parents of children with
      RRP referred to the authors' hospital completed a detailed epidemiological
      questionnaire at the initial visit or at the first return visit after the study
      began. At the first endoscopic debridement after study enrollment, tissue was
      obtained and submitted for HPV typing using polymerase chain reaction techniques
      and in situ hybridization. Staging of disease severity was performed in real time
      at each endoscopic procedure using an RRP scoring system developed by one of the
      authors (B.J.W.). The frequency of endoscopic operative debridement was recorded
      for each patient. Information in the database was analyzed to identify
      statistically significant relationships between extent of disease and/or HPV
      type, patient age at diagnosis, and selected epidemiological factors. RESULTS:
      The study may represent the first longitudinal prospective analysis of a large
      pediatric RRP population. Fifty-eight of the 73 patients in the study underwent
      HPV typing. Patients infected with HPV-11 were significantly more likely to have
      higher severity scores, require more frequent surgical intervention, and require
      adjuvant therapy to control disease progression. In addition, patients with HPV
      11 RRP were significantly more likely to develop tracheal disease, to require
      tracheotomy, and to develop pulmonary disease. Patients receiving a diagnosis of
      RRP before 3 years of age had significantly higher severity scores, higher
      frequencies of surgical intervention, and greater likelihood of requiring
      adjuvant medical therapy. Patients with Medicaid insurance had significantly
      higher severity scores and required more frequent surgical debridement. Birth by
      cesarean section appeared to be a significant risk factor for more severe disease
      and necessity of more frequent surgical intervention. CONCLUSION: Statistical
      analysis of the relationships among epidemiological factors, HPV type, and
      clinical course revealed that patients with HPV-11 and patients younger than 3
      years of age at RRP diagnosis are prone to develop more aggressive disease as
      represented by higher severity scores at endoscopic debridement, more frequent
      operative debridement procedures per year, a greater requirement for adjuvant
      therapy, and greater likelihood of tracheal disease with tracheotomy.

PMID- 15514561
TI  - Targeting gastrin-releasing peptide receptors for cancer treatment.
AB  - Growth factor receptors play critical roles in cancer cell proliferation and
      progression. A number of such receptors have been targeted for cancer treatment
      by either a monoclonal antibody or a specifically designed small molecule to
      inhibit the receptor function. Bombesin/gastrin-releasing peptide receptors
      (BN/GRP-Rs) are expressed in a variety of cancer cells and have limited
      distribution in normal human tissue. Inhibition of BN/GRP-Rs has been shown to
      block small cell lung cancer growth in vitro. Early phase clinical trials
      targeting human GRP-R showed anti-cancer activity. This review will focus on the
      study of the distribution of BN/GRP-Rs in normal and malignant tissues, and
      various approaches to targeting BN-GRP-Rs for cancer diagnosis and treatment.

PMID- 15514562
TI  - Antitumor triptycene bisquinones induce a caspase-independent release of
      mitochondrial cytochrome c and a caspase-2-mediated activation of initiator
      caspase-8 and -9 in HL-60 cells by a mechanism which does not involve Fas
      signaling.
AB  - Synthetic triptycene analogs (TT code number) mimic the antitumor effects of
      daunorubicin (DAU) in vitro, but have the advantage of blocking nucleoside
      transport, inhibiting both DNA topoisomerase I and II activities, and retaining
      their efficacy in multidrug-resistant (MDR) tumor cells. Since TT bisquinones
      induce poly(ADP-ribose) polymerase-1 (PARP-1) cleavage at 6 h and
      internucleosomal DNA fragmentation at 24 h, which are, respectively, early and
      late markers of apoptosis, these antitumor drugs were tested for their ability to
      trigger the release of mitochondrial cytochrome c (Cyt c) and the caspase
      activation cascade in the HL-60 cell system. Based on their ability to reduce the
      viability of wild-type, drug-sensitive HL-60-S cells in the nanomolar range, six
      lead antitumor TT bisquinones have been identified so far: TT2, TT13, TT16, TT19,
      TT24 and TT26. In accord with the fact that effector caspase-3 is responsible for
      PARP-1 cleavage, 4 microM concentrations of DAU and these TT bisquinones all
      maximally induce caspase-3 activity at 6 h in HL-60-S cells, an effect which
      persists when the drugs are removed after a 1-h pulse treatment. Since caspase-3
      may be activated by initiator caspase-9 and -8, it is significant to show that
      such caspase activation cascade is induced by 4 microM DAU and TT bisquinones at
      6 h in HL-60-S cells. Although the relationship is not perfect, the ability of TT
      analogs to induce caspase-3, -8 and -9 activities may be linked to their quinone
      functionality and cytotoxicity. Interestingly, 4 microM concentrations of TT
      bisquinones retain their ability to induce caspase-3, -8 and -9 activities at 6 h
      in the MDR HL-60-RV cell line where 4 microM DAU becomes totally ineffective. The
      release of mitochondrial Cyt c is also detected within 6 h in HL-60-S cells
      treated with 4 microM DAU or TT bisquinones, a finding consistent with the fact
      that Cyt c is the apoptotic trigger that activates caspase-9. Caspase-2 and -8
      may both act upstream of mitochondria to promote Cyt c release, but caspase-2 is
      already maximally activated 6 h after 4 microM DAU or TT13 treatments, whereas
      DAU- or TT-induced caspase-8 and -9 activities peak at 9 h. Pre-treatments with
      15 microM of the caspase-2 inhibitor benzyloxycarbonyl (z)-Val-Asp-Val-Ala-Asp
      (VDVAD)-fluoromethyl ketone (fmk) totally block DAU- and TT13-induced caspase-2, 
      8 and -9 activities, whereas pre-treatments with 15 microM of the caspase-8
      inhibitor z-Ile-Glu-Thr-Asp (IETD)-fmk prevent DAU and TT13 from inducing caspase
      8 activities without affecting their caspase-2- and -9-inducing activities,
      suggesting that the induction of apical caspase-2 activity by these drugs may be
      a critical upstream event required for the activation of other downstream
      caspases, including caspase-9 and the mitochondrial amplification loop through
      caspase-8. However, the mechanisms by which DAU and TT13 induce the release of
      mitochondrial Cyt c appear to be caspase-independent since they are both
      insensitive to similar pre-treatments with 100 microM of these specific caspase-2
      and -8 inhibitors. Moreover, pre-treatments with 10 microg/ml of the antagonistic
      anti-Fas DX2 and ZB4 monoclonal antibodies (mAbs), and the neutralizing anti-Fas
      ligand (FasL) NOK-1 mAb are all unable to prevent DAU and TT13 from inducing Cyt
      c release and caspase-2, -8 and -9 activities, suggesting that the Fas-FasL
      signaling pathway is not involved in the mechanism by which these quinone
      antitumor drugs trigger apoptosis in HL-60 cells.

PMID- 15514563
TI  - Peptide-vector strategy bypasses P-glycoprotein efflux, and enhances brain
      transport and solubility of paclitaxel.
AB  - We present the results obtained with paclitaxel coupled to a peptide-vector SynB3
      (PAX-OSUC-SynB3), showing that this peptide-vector enhances the solubility of
      paclitaxel and its brain uptake in mice using the in situ brain perfusion model.
      We also show by the in situ brain perfusion in P-glycoprotein (P-gp)-deficient
      and wild-type mice that vectorized paclitaxel bypasses the P-gp present at the
      luminal side of the blood-brain barrier. The effect of the vectorized paclitaxel
      on various cancer cells was not significantly different from that of free
      paclitaxel. These results indicate that vectorization of paclitaxel may have
      significant potential for the treatment of brain tumors.

PMID- 15514564
TI  - Ligands of peroxisome proliferator-activated receptor gamma induce apoptosis in
      multiple myeloma.
AB  - The activation of proliferator-activated receptor gamma (PPAR-gamma) by its
      natural and synthetic ligands induces apoptosis in several tumor cell lines,
      including malignant B-lineage cells. We investigated whether treatment with
      pioglitazone (PGZ), rosiglitazone (RGZ) or 15-deoxy-Delta12,14-prostaglandin J2
      (15d-PGJ2) inhibited tumor cell growth in five human multiple myeloma cell lines
      (LP-1, U-266, RPMI-8226-S, OPM-2 and IM-9) and human bone marrow myeloma cells
      expressing PPAR-gamma protein. MTT assays revealed growth arrest induced by the
      natural activator of PPAR-gamma 15d-PGJ2 and a lower antiproliferative effect
      with thiazolidinediones (PGZ and RGZ) in a dose-dependent manner. Induction of
      apoptosis was indicated by Annexin-V staining. At a dose of 50 microM, 15d-PGJ2
      led to a high rate of apoptosis in all cell lines (60-92%). Furthermore,
      induction of apoptosis in sorted bone marrow plasma cells from myeloma patients
      was detected. Thiazolidinediones comprise anti-myeloma activity in vitro and
      should be explored further for the treatment of multiple myeloma.

PMID- 15514565
TI  - G2/M blockade by paclitaxel induces caveolin-1 expression in A549 lung cancer
      cells: caveolin-1 as a marker of cytotoxicity.
AB  - Caveolins are highly expressed in terminally differentiated cells, but this
      expression is down-regulated in various cancer cell lines. Exposure to low doses
      of paclitaxel (taxol) is sufficient to up-regulate caveolin-1, suggesting that a
      mild cytotoxic stress induces a response implying caveolin and caveolae. Here we
      show that this up-regulation is sustained even after the cessation of paclitaxel
      treatment. After exposure to a cytostatic dose of paclitaxel (50 nM), A549 lung
      cancer cells are blocked in the G2/M cell cycle phase. After removal of
      paclitaxel, cell death occurs, accompanied with an increase in caveolin
      expression, suggesting an effect of caveolin in this process. Three days post
      paclitaxel treatment, surviving A549 cells were passaged and only a half of them
      adhered to the culture dish. Adhering cells (still mainly in the G2/M cell cycle
      phase) were still unable to grow and progressively entered in an apoptotic state.
      This study suggests that effects of a low dose of paclitaxel were still present
      even 1 week after drug removal and that caveolin-1 is a good marker of
      cytotoxicity.

PMID- 15514566
TI  - Lack of contribution of dihydrofluorouracil and alpha-fluoro-beta-alanine to the
      cytotoxicity of 5'-deoxy-5-fluorouridine on human keratinocytes.
AB  - Capecitabine (Xeloda) is a very active oral fluoropyrimidine (colon and breast
      cancers) whose clinical use is complicated by the presence of hand-foot syndrome
      (HFS). This cutaneous toxicity is less frequently encountered with other oral
      fluoropyrimidines containing a dihydropyrimidine dehydrogenase (DPD) inhibitor.
      The HFS is thus attributed to the presence of the main 5-fluorouracil (5-FU)
      metabolites, dihydrofluorouracil (5-FUH2) and alpha-fluoro-beta-alanine (FBAL),
      but without strong pharmacological arguments. The aim of the present study was to
      closely examine this latter hypothesis. Capecitabine generates 5'
      deoxyflourouridine (5'-DFUR) which is transformed into 5-FU at the cellular
      target site through the intermediary of thymidine phosphorylase (TP). The
      cytotoxic effects (MTT test, 4-day exposure) of 5'-DFUR, 5-FU, 5-FUH2 and FBAL
      were tested against the spontaneously immortalized human keratinocyte cell line
      (HaCaT) and the human cancer colon cell line WiDr as a control. Mean IC50s on
      HaCaT and WiDr were, respectively, 1.3 and 10 microM for 5'-DFUR, 0.2 and 3.3
      microM for 5-FU, 13.4 and 560 microM for 5-FUH2, and greater than 650 and 6500
      microM for FBAL. The respective 5'-DFUR IC50s values were not different when
      cells were exposed to 5'-DFUR alone or in combination with 5-FU, 5-FUH2 and FBAL
      in both cell lines, the relative proportion of each drug reflecting known
      pharmacokinetic data for capecitabine (5'-DFUR 12.4%, 5-FUH2 6.4%, 5-FU 1.2% and
      FBAL 80%). This latter finding demonstrates the relative lack of significant
      cytotoxic activity of 5-FUH2 and FBAL on human keratinocytes. TP activity was
      particularly high in HaCaT cells and DPD activity was very low in both cell
      lines. These data strongly suggest that the presence of 5-FU metabolites does not
      play a major role in the HFS generated by capecitabine and that it can probably
      be attributed to particularly high TP activity in keratinocytes. This observation
      may have important clinical consequences such as a possible local pharmacological
      inhibition of TP for controlling HFS.

PMID- 15514567
TI  - Cytostatic and pro-apoptotic effects of a novel phenylacetate-dextran derivative
      (NaPaC) on breast cancer cells in interactions with endothelial cells.
AB  - We have tested a novel hybrid molecule made of carboxymethylbenzylamide dextran
      (CMDB) and sodium phenylacetate (NaPa) groups, called the CMDB-NaPa ester
      (NaPaC), on the proliferation of breast cancer and endothelial cells as well as
      paracrine effects between these two cell types. Our results showed that NaPaC
      inhibited the proliferation of MDA-MB-231 cells and MCF-7 cells in a dose
      dependent manner. NaPaC was 20-fold more active on highly invasive MDA-MB-231
      cells than the NaPa parental molecule. On MCF-7 cells, which present a less
      aggressive phenotype, NaPaC was only 3-fold more active than the NaPa parental
      molecule. Furthermore, NaPaC had only a slight effect on the proliferation of
      primary cultured endothelial cells (HUVEC). A cytostatic effect of NaPaC on tumor
      cells was observed with cells accumulating in G0/G1 phase after 96 h of
      treatment. In addition, NaPaC induced a strong apoptotic effect on the two breast
      cancer cell lines. Conditioned media (CM) from tumor cells inhibited HUVEC
      proliferation, and this effect was enhanced in the presence of NaPaC (6 mM) and
      NaPa (10 mM). In addition to this cytostatic effect, CM from tumor cells induced
      a HUVEC early apoptosis which was increased, mainly, in the presence of NaPa (15
      mM). Thus, this study shows that NaPaC is a more powerful anti-proliferative
      molecule than its parental NaPa molecule, with cytostatic and pro-apoptotic
      effects on MDA-MB-231 and MCF-7 tumor cells. Also, both molecules increased a pro
      apoptotic effect of tumor cells on HUVEC.

PMID- 15514568
TI  - The allylic 7-ketone at the steroidal skeleton is crucial for the antileukemic
      potency of chlorambucil's active metabolite steroidal esters.
AB  - We have investigated the role of the allylic 7-ketone in oxidized Delta5-steroids
      on antileukemic activity. We synthesized and studied a series of oxidized and non
      oxidized steroidal esters of p-N,N-bis(2-chloroethyl)aminophenylacetic acid
      (PHE), chlorambucil's active metabolite. In a comparative study of these 7-keto
      derivatives, on a molecular basis, regarding their ability to induce sister
      chromatid exchanges (SCEs) and to inhibit cell proliferation in normal human
      lymphocytes in vitro, the results with these 7-keto derivatives, on a molecular
      basis, correlated well with their antileukemic potency against leukemia P388- and
      L1210-bearing mice, which proved to be significantly increased compared to that
      of the non-oxidized derivatives. Our results indicate that the role of the
      steroidal skeleton it is not only for the transportation of the alkylating agent
      into the cell, but also contributes directly to the mechanism of antileukemic
      action, by an as-yet unknown way. The main conclusion from this study is that the
      existence of the allylic 7-keto group in the skeleton of the Delta5-steroidal
      esters impressively enhances their antileukemic activity, while the toxicity
      remains at clinically acceptable levels, suggesting that this structural
      modification should be further investigated.

PMID- 15514570
TI  - Guillain-Barre syndrome in a patient with metastatic colon cancer receiving
      oxaliplatin-based chemotherapy.
AB  - We report Guillain-Barre syndrome (GBS), developed in a patient with metastatic
      colon cancer, receiving oxaliplatin-based chemotherapy. The 53-year-old patient
      was treated with first-line chemotherapy consisting of oxaliplatin 45 mg/m2, 5
      fluorouracil 450 mg/m2 and folinic acid 200 mg/m2, all given on the same day in a
      weekly schedule. After 13 weeks of treatment and a cumulative oxaliplatin dose of
      585 mg/m2, the patient developed unsteadiness of gait, dysphagia, and weakness of
      both the upper and lower limbs, as well as impairment of all sensory modalities.
      Clinical examination, computed tomography and magnetic resonance imaging scans of
      the brain, blood tests, nerve conduction studies, and cerebrospinal fluid
      analysis confirmed the diagnosis of GBS. Intravenous immunoglobulin G was
      administered for 5 days and the patient recovered fully. Oxaliplatin can cause
      acute and delayed neurotoxicity, but this is the first report of GBS in a patient
      receiving oxaliplatin-based chemotherapy. Elevation of pro-inflammatory
      cytokines, such as tumor necrosis factor-alpha and interleukin-6, induced by
      oxaliplatin, may represent the relevant causal links involved in the cascade of
      events which have led to the immune-mediated demyelination in the peripheral
      nervous system in this patient.

PMID- 15514569
TI  - Activity of MDI-301, a novel synthetic retinoid, in xenografts.
AB  - The efficacy of MDI-301, a non-toxic novel synthetic retinoid, was found to be
      equivalent to the natural 9-cis-retinoic acid (RA) in vitro against estrogen
      dependent MCF7 and T47D breast cancer cell lines which express RA receptor (RAR)
      alpha. Both retinoids also showed similar efficacy against established PC-3
      prostate carcinoma xenografts. MCF7 tumor xenografts showed a reduction in tumor
      growth of 48% without systemic side-effects upon treatment with MDI-301 compared
      with MCF7 controls. Tumor xenografts derived from MDA-MB-231, an estrogen
      independent breast cancer cell line that expresses low levels of RARalpha, were
      unresponsive. This study demonstrates that MDI-301 is as efficacious as 9-cis-RA
      against cancer cells with RARalpha, with no signs of toxicity in vivo, making it
      a potential candidate for cancer therapy.

PMID- 15514571
TI  - Drug-eluting stents: from randomized trials to the real world.
AB  - Drug-eluting stents have been developed to prevent in-stent restenosis following
      percutaneous coronary revascularization. In a number of randomized trials,
      polymer-coated sirolimus- and paclitaxel-eluting stents have been proven to
      markedly reduce the incidence of angiographic restenosis and repeat
      revascularization when compared to bare metal stents. Effectiveness of sirolimus
      eluting stents in the prevention of restenosis has been confirmed in many subsets
      of patients and lesions not included in randomized trials, such as in-stent
      restenosis, chronic total occlusion, acute myocardial infarction, and others.
      Very promising data in the real world are emerging for utilization of paclitaxel
      eluting stents as well. Other drug-eluting stents gave less brilliant results or
      even true failures, whilst a number of new drugs and stent platforms are under
      clinical or preclinical evaluation. In this review we describe the main clinical
      trials on drug-eluting stents, and the most recent informations derived from
      observational studies and registries. Moreover, preliminary results on new drug
      eluting stents are summarized.

PMID- 15514572
TI  - Coronary bifurcation stenting. Current techniques, outcome and possible future
      developments.
AB  - Percutaneous treatment of coronary bifurcation lesions remained challenging in
      the stent era, with restenosis rates greater than 30% and no advantage from the
      routine use of kissing stents. Drug eluting stents (DES) have dramatically
      reduced the restenosis rates (RR) in the main vessel, but with conventional T
      stenting double digits figures are still reported for the side-branch because of
      poor ostial coverage. The techniques of kissing stenting able to provide full
      lesion coverage (Culotte, V-stenting, Crush) have the potential to improve these
      results but the development of dedicated DES is probably needed to obtain
      consistently high procedural and long-term success.

PMID- 15514573
TI  - Saphenous vein graft disease.
AB  - Saphenous vein graft (SVG) disease has been an obstinate problem facing the
      cardiologist since the early days of coronary artery bypass grafting (CABG)
      surgery. SVG disease follows temporally distinct phases of thrombosis, intimal
      hyperplasia and progressive atherosclerosis leading to recurrent ischemia which
      can be treated with repeat operation or percutaneous revascularization. However,
      repeat operation is associated with high mortality and morbidity. Also,
      percutaneous treatment of SVG disease is complicated by a high rate of procedural
      and long term complications due to the interrelated phenomena of distal
      embolization, slow flow or no reflow, periprocedure myocardial infarction, and
      subsequent restenosis. Long-term patency is poor in this patient population
      regardless of the treatment modality. Many pharmaceutical and device based
      approaches have been tested to avert these complications, but few, such as the
      use of distal protection devices, have shown benefit. The novel drug-eluting
      stents show promise in reducing the occurrence of restenosis and solving one of
      the problems associated with the percutaneous treatment of SVG disease. The
      pathogenesis and therapeutic options for SVG disease is reviewed in this article.

PMID- 15514574
TI  - Intravascular ultrasound assessment of coronary atherosclerosis and percutaneous
      interventions.
AB  - Intravascular ultrasound (IVUS) is a catheter-based technique which provides high
      resolution cross-sectional images of both, coronary lumen and vessel wall.
      Various scientific studies recently established IVUS as a valuable tool for the
      assessment of the natural history of coronary atherosclerosis and the effect of
      different pharmacological and non-pharmacological interventions on progression
      regression of atherosclerosis. Novel technical approaches that use IVUS
      radiofrequency data may provide further interesting information on vessel wall
      characteristics but require further validation. In addition, numerous trials
      applied IVUS to assess the short- and long-term outcome of different percutaneous
      coronary interventions, including the implantation of drug-eluting stents.
      Besides the importance of IVUS in the field of scientific trials, IVUS can be
      clinically helpful for the evaluation of angiographically ambiguous lesions,
      guidance of catheter-based interventions, and management of complications.
      Settings in which IVUS may be particular useful are: ostial and bifurcation
      lesions; the presence of diffuse atherosclerotic disease; severely calcified or
      very tight lesions; relatively small vessels; diabetic patients; and if multiple,
      long or novel stents are implanted. This article gives an overview on the value
      of IVUS for the assessment of coronary atherosclerosis and percutaneous coronary
      interventions. In this context, we reviewed a selection of recently published
      IVUS studies which provide interesting new information in this field.

PMID- 15514575
TI  - Non-interventional cardiac diagnostics: computed tomography, magnetic resonance
      and real-time three-dimensional echocardiography. Techniques and clinical
      applications.
AB  - New cardiovascular imaging modalities, including computed tomography (CT),
      magnetic resonance (MR) imaging and real-time three-dimensional echocardiography,
      have great potential for providing important and additional information
      concerning cardiac function and pathology. With significant and extremely fast
      technical improvements, non-invasive cardiac imaging has become a focal point in
      the diagnosis of cardiac disease. Thereby CT has been shown to allow the
      visualization of coronary arteries concerning calcifications, significant
      stenoses and coronary plaques, whereas MR imaging demonstrated its ability to
      evaluate cardiac morphology and function as well as perfusion imaging and
      viability assessment. As CT and MR, real-time three-dimensional echocardiography
      has increasingly progressed in the last years offering the potential for routine
      clinical application, e.g. in the evaluation of valve disease, the assessment of
      left ventricular thrombi or the guidance of intracardiac catheter placement. This
      article will provide a brief overview of each technique, possible clinical
      applications and their perspectives. Because both, CT and MR, have been
      successfully applied to visualize the coronary arteries, this article focuses on
      the abilities and limitations of CT and MR coronary artery imaging.

PMID- 15514576
TI  - The prevention of contrast-induced nephropathy in patients undergoing
      percutaneous coronary intervention.
AB  - Contrast-induced nephropathy (CIN) is a leading cause of morbidity and mortality
      in high-risk patients undergoing percutaneous coronary intervention (PCI) or
      other radiocontrast procedures. Approximately 25% of all patients selected for
      these procedures are at risk for its development. Patients who experience this
      complication have higher rates of mortality, longer hospital stays and poorer
      long-term outcomes. The occurrence of CIN is directly related to the number of co
      existing clinical risk factors. Among the many risk factors, preexisting renal
      impairment, advanced age, the presence of diabetes mellitus and both the volume
      and type of the contrast agent administered are among the most important. While
      the precise pathophysiological mechanisms responsible for this condition are
      complex and incompletely understood, experimental studies suggest that the
      pathogenesis involves a combination of renal ischemia and direct tubular
      epithelial cell toxicity. At the present time, adequate periprocedural hydration
      and the selection of low-osmolar and, more recently, iso-osmolar contrasts agents
      are the only available tools to the operator for reducing the risk of this
      complication. Several other modalities, such as the use of NaHCO3 and
      hemofiltration, also appear promising in preventing the development of this
      complication. This article reviews the epidemiology, pathophysiology, and
      consequences of CIN. It also reviews the risk factors for the development of CIN,
      as well as the history of the various modalities studied in its prevention.

PMID- 15514577
TI  - New and viable cells to replace lost and malfunctioning myocardial tissue.
AB  - The use of stem cells for cardiac repair is a promising opportunity for
      developing new treatment strategies as the applications are theoretically
      unlimited and lead to actual cardiac tissue regeneration. Human embryonic stem
      cells were only recently cloned and their capacity to differentiate into true
      cardiomyocytes makes them in principle an unlimited source of transplantable
      cells for cardiac repair, although practical and ethical constraints exist. Also,
      the study of embryonic stem cells and their differentiation into cardiomyocytes
      will bring forth new insights into the molecular processes involved in
      cardiomyocyte-development and -proliferation, which could lead to the development
      of other strategies to augment in vivo cardiomyocyte numbers. On the other hand,
      somatic stem cells are alternative cell sources that can be used for cell
      transplantation purposes. They do not evoke ethical issues and bear less ethical
      constraints. However, they also appear to be much more restricted in their
      differentiation potential than the embryonic stem cells. Here we discuss the use
      of both cell types, embryonic and somatic stem cells, in relation with their
      importance for the clarification of cardiomyocyte-development and their possible
      usefulness for clinical therapy.

PMID- 15514578
TI  - Vascular diagnosis laboratory. Workloads and indications.

PMID- 15514579
TI  - Chlamydia screening among sexually active young female enrollees of health plans-
      United States, 1999-2001.
AB  - Chlamydia trachomatis infection is the most commonly reported sexually
      transmitted disease (STD) in the United States, with the highest rates among
      adolescent females and young women. Approximately 5%-14% of routinely screened
      females aged 16-20 years and 3%-12% of women aged 20-24 years are infected with
      chlamydia. Because up to 70% of chlamydial infections in women are asymptomatic,
      routine screening and treatment of infected persons is essential to prevent
      pelvic inflammatory disease, infertility, ectopic pregnancy, and perinatal
      infections. Since the 1990s, CDC, the U.S. Preventive Services Task Force, and
      several clinical organizations have recommended routine screening for chlamydial
      infection for all sexually active women aged <26 years and for pregnant women of
      all ages. To evaluate rates of chlamydia screening among sexually active young
      females, CDC analyzed 1999-2001 data from the Health Plan Employer Data and
      Information Set (HEDIS) reported by commercial and Medicaid health insurance
      plans. This report summarizes the results of that analysis, which determined that
      screening rates were low despite slight increases in screening covered both by
      commercial and Medicaid plans during 1999-2001. Increased screening by health
      care providers and coverage of screening by health plans will be necessary to
      reduce substantially the burden of chlamydial infection in the United States.

PMID- 15514580
TI  - Lymphogranuloma venereum among men who have sex with men--Netherlands, 2003-2004.
AB  - Lymphogranuloma venereum (LGV) is a systemic, sexually transmitted disease (STD)
      caused by a variety of the bacterium Chlamydia trachomatis that rarely occurs in
      the United States and other industrialized countries; the prevalence of LGV is
      greatest in Africa, Southeast Asia, Central and South America, and Caribbean
      countries. However, in the Netherlands, which typically has fewer than five cases
      a year, as of September 2004, a total of 92 cases of LGV had been confirmed
      during the preceding 17 months among men who have sex with men (MSM). The first
      13 cases, diagnosed during April-November 2003, were reported by local health
      authorities in Rotterdam in December 2003. An alert was sent to the Early Warning
      and Reporting System of the European Union and to the European Surveillance of
      Sexually Transmitted Infections Network (ESSTI). In April 2004, a report was made
      to CDC, and state and local health departments were alerted. Of the 92 cases
      confirmed in the Netherlands, 30 occurred during 2003 and 62 during 2004. This
      report describes the ongoing investigation of the LGV outbreak. Health-care
      providers should be vigilant for LGV, especially among MSM exposed to persons
      from Europe, and prepared to diagnose the disease and provide appropriate
      treatment to patients and their exposed sex partners.

PMID- 15514581
TI  - Laboratory exposure to Burkholderia pseudomallei--Los Angeles, California, 2003.
AB  - On July 26, 2003, the Los Angeles County Department of Health Services (LACDHS)
      received a report that a local clinical laboratory had isolated from specimens
      Burkholderia pseudomallei, a category B biologic terrorism agent and the
      causative organism for melioidosis, which is endemic to certain tropical areas.
      Because laboratory workers had manipulated cultures of the organism, CDC was
      asked to assist in the subsequent investigation. This report summarizes the
      results of that investigation, which included assessment of laboratory exposures,
      postexposure chemoprophylaxis, and serologic testing of exposed laboratory
      workers. The findings underscore the need to reinforce proper laboratory
      practices and the potential benefits of chemoprophylaxis after laboratory
      exposures.

PMID- 15514582
TI  - Laboratory surveillance for wild and vaccine-derived polioviruses, January 2003
      June 2004.
AB  - In 1988, the World Health Assembly resolved to eradicate poliomyelitis globally
      by 2000. Progress toward achieving this goal has been reported from countries
      where polio is endemic, and three World Health Organization (WHO) regions
      (Americas, Europe, and Western Pacific) appear to be free of indigenous wild
      poliovirus (WPV) transmission. One key strategy for eradicating polio is
      establishing sensitive polio surveillance systems by investigating acute flaccid
      paralysis (AFP) cases. To ensure that specimens from persons with AFP undergo
      appropriate processing for viral isolation, WHO established a global polio
      laboratory network in 1988. This report updates previous publications, summarizes
      the laboratory network's performance, and describes the location and
      characterization of WPV and vaccine-derived poliovirus (VDPV) during January 2003
      June 2004.

PMID- 15514583
TI  - Update: influenza activity--United States and worldwide, May-October 2004.
AB  - May-October 2004, influenza A (H3N2) viruses circulated worldwide and were
      associated with mild-to-moderate levels of disease activity. Influenza A (H1N1)
      and B viruses were reported less frequently. In North America, isolates of
      influenza A (H3N2), A (H1N1), and B were identified sporadically. This report
      summarizes influenza activity in the United States and worldwide during May
      October 2004. Influenza activity in North America typically peaks during December
      March.

PMID- 15514584
TI  - West Nile virus activity--United States, October 20-26, 2004.
AB  - During October 20-26, a total of 80 cases of human West Nile virus (WNV) illness
      were reported from 16 states (Arizona, California, Florida, Iowa, Kentucky,
      Louisiana, Michigan, Mississippi, Missouri, Montana, Nebraska, New York, Ohio,
      South Dakota, Texas, and Utah).

PMID- 15514585
TI  - Increased levels of serum transferrin receptor and serum transferrin receptor/log
      ferritin ratios in men with prostate cancer and the implications for body-iron
      stores.
AB  - The serum transferrin receptor (sTfR) is a sensitive indicator of iron-deficiency
      erythropoiesis that is not affected by inflammation. Concentrations of this
      molecule are inversely correlated with body-iron stores, and increased body-iron
      stores are associated with an increased risk of cancer of the liver and lungs.
      However, an association between iron status as assessed on the basis of sTfR and
      prostate cancer has not been previously investigated. We measured sTfR and serum
      ferritin by means of an enzyme immunoassay in 27 men with newly diagnosed,
      untreated prostate cancer and in 72 controls. Our study population ranged in age
      from 38 to 78 years. The mean serum ferritin concentration in men with prostate
      cancer was 44.8% lower than that in men without this tumor ( P < .05). In
      contrast, the mean values of sTfR and sTfR/log serum ferritin were 32% and 60%
      higher, respectively, in men with prostate cancer than in those without this
      tumor ( P < .05). Differences between groups persisted after we took into account
      inflammation (alpha 1-acid glycoprotein > 1 g/L, C-reactive protein > 10 mg/L; P
      < .05). Among the entire study population and among men without inflammation, a
      higher percentage of subjects (29%-31%) than of controls (14%-22%) had sTfR
      values greater than 8 mg/L, suggestive of iron-deficiency erythropoiesis ( P <
      .05). The odds ratios for men with prostate cancer to have sTfR values of less
      than 2.9 mg/L (suggestive of increased body-iron stores) was 0, compared with
      1.745 to 3.65 for the same men to have sTfR values greater than 8 mg/L. sTfR was
      negatively correlated with log ferritin ( r = -.422, P < .05) but did not
      correlate with tissue inflammation, tumor stage, or acute-phase proteins. It
      appears that prostate cancer is not associated with increased body-iron stores.

PMID- 15514586
TI  - Effects of double blockade of CD28 and inducible-costimulator signaling on anti
      glomerular basement membrane glomerulonephritis.
AB  - Inducible costimulator (ICOS) is the third member of the CD28 superfamily,
      expressed on antigen-primed T-cells, enhancing Th2 differentiation. Anti
      glomerular basement membrane (anti-GBM) glomerulonephritis results from multiple
      effects generated by both Th1 and Th2 cells. To evaluate the contribution of
      these T-cells to the progression of anti-GBM glomerulonephritis, we investigated
      the effect of double blockade of CD28 and ICOS signaling. Anti-GBM
      glomerulonephritis was induced in C57BL/6 mice, a Th1-prone strain. CD28
      signaling was inhibited with the use of fusion proteins of cytolytic T-lymphocyte
      associated antigen-4 (CTLA4 immunoglobulin) and ICOS signaling by the monoclonal
      antibody (mAb) for ICOS. Blood and urine samples were collected 5 and 14 days
      after induction of anti-GBM glomerulonephritis. Mice were killed to facilitate
      histopathologic analyses at the same time. Anti-GBM glomerulonephritis was
      prevented from functionally deteriorating (eg, proteinuria or increasing serum
      creatinine) by CTLA4 immunoglobulin or anti-activation-inducible lymphocyte
      immunomodulatory molecule (AILIM) mAb as an anti-ICOS mAb. Nevertheless, double
      or single blockade of ICOS signaling showed a weaker inhibitory effect than
      single blockade of CD28 signaling in terms of the serum immunoglobulin level and
      histopathologic change. There is no synergistic effect between CTLA4
      immunoglobulin and anti-AILIM mAb when simultaneously administered in
      experimental anti-GBM glomerulonephritis. Double blockade of both CD28 signaling
      and ICOS signaling is effective for preventing functional deterioration in this
      model. However, CD28 single blockade is more effective than double blockade both
      serologically and histopathologically.

PMID- 15514587
TI  - Gene expression in giant-cell tumors.
AB  - Malignant transformation is thought to be associated with changes in the
      expression of a number of genes, and this alteration in gene expression is
      considered critical to the development of the malignant phenotype. In this study,
      gene expression in 8 samples of giant-cell tumor (GCT) of bone, as well as in
      bone at the site of osteoarthritis and in a variety of normal tissues, was
      determined at Gene Logic Inc (Gaithersburg, Md) with the use of Affymetrix
      GeneChip U_133 arrays containing approximately 40,000 genes/expressed sequence
      tags (ESTs). Gene-expression analysis was performed with the use of the Gene
      Logic GeneExpress Software System. Differences in gene expression between GCTs
      and bone were observed. In addition, genes expressed uniquely in GCTs among these
      and 519 samples from 20 other tissue types were identified. Some of the genes
      that were found to be overexpressed in GCTs, such as tartrate-resistant acid
      phosphatase and the lysosomal H + -transporting ATPase, are also expressed by
      osteoclasts. Osteoprotegrin ligand (OPGL) was also selectively overexpressed in
      GCTs. The genes found to be overexpressed in GCTs appear to reflect the genetic
      profile of osteoclast-lineage cells and also the genetic profile of an
      osteoclastogenic environment. The genes identified in this study may play a role
      in the pathogenesis of GCTs, confirm the likely importance of OPGL in GCT
      pathogenesis, and may indicate other possible targets to which antitumor therapy
      could be directed.

PMID- 15514588
TI  - Generation of a human leukocyte antigen-A24-restricted antitumor cell with the
      use of SART-1 peptide and dendritic cells in patients with malignant brain
      tumors.
AB  - Dendritic cells (DCs) can be the principal initiators of antigen-specific immune
      responses. In this study, we attempted to generate cytotoxic T-lymphocytes (CTLs)
      using DCs pulsed with SART-1(254) peptide. Peripheral-blood mononuclear cells
      (PBMCs) and tumor-infiltrating mononuclear cells (TIMCs) were obtained from 11
      patients with brain tumors expressing human leukocyte antigen (HLA)-A24. After
      stimulation with SART-1(254) peptide, CTLs showing over 15% were observed in one
      of 4 patients with gliomas and in 4 of 7 patients with metastatic brain tumors.
      Furthermore, exposure to DCs pulsed with SART-1(254) peptide increased the
      killing activity of these CTLs by 28.7% and 37.5%, respectively. We conclude that
      DCs pulsed with SART-1(254) peptide are effective in generating HLA-A24
      restricted antitumor cells.

PMID- 15514589
TI  - Fungal susceptibility to zinc deprivation.
AB  - Calprotectin is a neutrophil-derived antimicrobial protein that competes with
      microorganisms for zinc. The zinc-specific effect of calprotectin against Candida
      albicans appears to be related to this organism's marked susceptibility to
      deprivation of this metal. However, it is not known whether this susceptibility
      is particular to C albicans or whether it is a characteristic of pathogenic fungi
      in general. As a means of deciding between these 2 possibilities, we undertook
      the study reported here to compare the susceptibility to zinc deprivation of 6
      other pathogenic fungal species in addition to that of C albicans . We tested the
      effect of metals in reversing growth inhibition of the 7 fungi against abscess
      fluid supernatant (a source of calprotectin) and 3 chemical chelators. Data were
      expressed as the concentration of metal required to bring about 50% restoration
      of growth. Zinc was found to be much more potent than the other metals tested in
      reversing growth inhibition of all the organisms by human abscess fluid and all 3
      chemical chelators. Copper and manganese also had some effect. In some cases,
      chelator stability constants were higher for other metals than for zinc; in
      particular, although diethylenetriaminopentaacetic acid has a stability constant
      for iron almost 10(10) times greater than that for zinc, zinc was more effective
      than iron in reversing growth inhibition by this chelator against all of the
      organisms. These results suggest that marked susceptibility to zinc deprivation
      is a general characteristic of pathogenic fungi.

PMID- 15514590
TI  - Pathogenic molecular mechanisms in an animal model of fulminant hepatic failure:
      rabbit hemorrhagic viral disease.
AB  - In this study we sought to determine whether molecular mechanisms involved in the
      pathogenesis of fulminant hepatic failure are present in rabbits experimentally
      infected with rabbit hemorrhagic disease virus (RHDV). The activities of
      aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase,
      as well as bilirubin concentration, were found to be significantly increased 36
      hours after infection. Infected animals also demonstrated significant decreases
      in factor VII activity, in the Fischer index, and in the deterioration of
      prothrombin time. The concentration of reduced glutathione was significantly
      decreased 36 hours after infection, and we noted a marked increase in the ratio
      of oxidized to reduced glutathione. Infected animals showed progressive decreases
      in liver activity of the antioxidant enzyme superoxide dismutase. Expression of
      hepatocyte growth factor and c-met was found to be progressively reduced from 24
      hours after infection, during which time we detected no modification in messenger
      RNA (mRNA) levels of transforming growth factor (TGF)-alpha. TFG-beta 1 was
      overexpressed 24 and 36 hours after infection, and 36 hours after infection we
      detected a significant increase in TNF-alpha mRNA levels. Experimental RHDV
      infection also induced marked activation of nuclear factor-kappaB and a
      significant increase in inducible nitric oxide synthase mRNA levels from 24 hours
      after infection. Data obtained from this animal model support its usefulness in
      the investigation of potential novel therapeutical modalities aimed at
      neutralizing reactive oxygen species and hepatocyte growth inhibitors or
      enhancing hepatocyte responsiveness to mitogens.

PMID- 15514591
TI  - Emergency conversion to cardiopulmonary bypass during attempted off-pump
      revascularization results in increased morbidity and mortality.
AB  - OBJECTIVE: We sought to evaluate outcomes and predictors of emergency conversion
      to cardiopulmonary bypass during attempted off-pump coronary bypass surgery.
      METHODS: From January 1999 through July 2002, 1678 consecutive isolated coronary
      artery bypass operations were performed at Lenox Hill Hospital, with the
      intention to treat all patients with off-pump coronary bypass surgery. Fifty
      (2.97%) patients required urgent conversion to cardiopulmonary bypass. All the
      preoperative, intraoperative, and postoperative variables were collected and
      analyzed in accordance with the New York State Cardiac Surgery Reporting System.
      Multivariate regression analysis was performed to determine predictors for
      conversion. RESULTS: In-hospital mortality and major morbidity were significantly
      lower in the nonconverted group compared with the converted patients (mortality:
      1.47% [n = 24] vs 12% [n = 6], P = .001; stroke: 1.1% [n = 18] vs 6% [n = 3], P =
      .02; renal failure: 1.23% [n = 20] vs 6% [n = 3], P = .02; deep sternal wound
      infection: 1.54% [n = 25] vs 8% [n = 4], P = .009; respiratory failure: 3.75% [n
      = 61] vs 28% [n = 14], P < .0001; nonconverted vs converted patients,
      respectively). The annual incidence of conversion decreased during the study
      period. There was a significant reduction in the incidence of conversion after
      routine use of a cardiac positioning device to performing lateral and inferior
      wall grafts (4.2% [n = 27] vs 2.3% [n = 23], P = .04). None of the preoperative
      variables were independent predictors of conversion on multivariate regression
      analysis. CONCLUSIONS: Because emergency conversion to cardiopulmonary bypass
      during attempted off-pump coronary bypass surgery results in significantly higher
      morbidity and mortality, studies comparing off-pump coronary bypass surgery with
      conventional coronary artery surgery should include converted patients in the off
      pump group. In our experience, emergency conversion is an unpredictable event.
      The incidence of conversion decreases with increasing experience of surgeons in
      performing off-pump coronary surgery and use of a cardiac positioning device.

PMID- 15514592
TI  - Valve-sparing aortic root replacement in bicuspid aortic valves: a reasonable
      option?
AB  - OBJECTIVES: Aortic dilatation occurs in many patients with bicuspid aortic
      valves. We have added root replacement using the remodeling technique originally
      designed for tricuspid aortic valves to bicuspid aortic valve repair for
      treatment of the dilated root. We compared the results of remodeling in bicuspid
      aortic valves with those in tricuspid aortic valves. METHODS: From October 1995
      through January 2004, 60 patients underwent root remodeling for bicuspid aortic
      valves (group A), and 130 patients underwent root remodeling for tricuspid aortic
      valves (group B). Correction of cusp prolapse was more often performed in group A
      (group A, 50/60; group B, 47/130; P < .0001). Transthoracic echocardiography was
      performed at 1 week, 6 and 12 months, and every year thereafter. Cumulative
      follow-up was 527 patient-years (mean, 2.9 +/- 2 years). RESULTS: No patient died
      in group A. Hospital mortality in group B was 5% (5/100; 95% confidence
      interval,1.6%-11.3%) after elective operations and 10% (3/30; 95% confidence
      interval, 2.1%-26.5%) after emergency operations. Mean systolic gradients were
      identical at 1 year (group A, 4.8 +/- 2.1 mm Hg; group B, 4.0 +/- 2 mm Hg) and 5
      years (group A, 4.5 +/- 2.3 mm Hg; group B, 3.9 +/- 2.2 mm Hg). Freedom from
      aortic regurgitation of grade 2 or higher at 5 years was 96% in group A and 83%
      in group B ( P = .07), and freedom from reoperation at 5 years was 98% in group A
      and 98% in group B ( P = .73). CONCLUSIONS: Valve-sparing aortic replacement with
      root remodeling can be applied to aortic dilatation and a regurgitant bicuspid
      aortic valve. Hemodynamic function and valve stability of a repaired bicuspid
      aortic valve are comparable with those seen in cases of tricuspid anatomy.

PMID- 15514593
TI  - Single-stage repair of extensive thoracic aortic aneurysms: experience with the
      arch-first technique and bilateral anterior thoracotomy.
AB  - BACKGROUND: Staged procedures for extensive aneurysmal disease of the thoracic
      aorta are associated with a substantial cumulative mortality (>20%) that includes
      hospital mortality for the 2 procedures and death (often from aortic rupture) in
      the interval between the 2 procedures. We have used a single-stage technique for
      operative repair of most or all of the thoracic aorta. METHODS: Forty-six
      patients with extensive disease of the thoracic aorta were managed with a single
      stage procedure by using a bilateral anterior thoracotomy and transverse
      sternotomy, hypothermic circulatory arrest, and reperfusion of the aortic arch
      vessels first to minimize brain ischemia. Thirty-one patients with chronic,
      expanding type A aortic dissections had previous operations for acute type A
      dissection (n = 22), aortic valve repair or replacement (n = 4), coronary artery
      bypass grafting (n = 4), or no previous operation (n = 1). The remaining 15
      patients had degenerative aneurysms (n = 12) or chronic type B dissections with
      proximal extension (n = 3). The ascending aorta and aortic arch were replaced in
      all patients combined with resection of various lengths of descending aorta
      (proximal one third [n = 19], proximal two thirds to three quarters [n = 22], or
      all [n = 5]). Coronary artery bypass grafting, valve replacement, or both were
      performed concomitantly in 19 patients. RESULTS: Hospital mortality was 6.5% (3
      patients). Morbidity included reoperation for bleeding (17%), mechanical
      ventilation for more than 72 hours (42%), temporary tracheostomy (13%), and
      temporary renal dialysis (9%). No patient sustained a stroke. There have been 5
      late deaths (3, 18, 34, 51, and 79 months postoperatively) unrelated to the
      aortic disease. Four patients have undergone successful reoperation on the aorta
      (false aneurysm [n = 1], endocarditis [n = 1], and progression of disease [n =
      2]). Five-year survival was 75%. CONCLUSION: The single-stage, arch-first
      technique is a safe and suitable alternative to the 2-stage procedure for repair
      of extensive thoracic aortic disease.

PMID- 15514594
TI  - Should the ascending aorta be replaced more frequently in patients with bicuspid
      aortic valve disease?
AB  - OBJECTIVE: The optimal diameter at which replacement of the ascending aorta
      should be performed in patients with bicuspid aortic valve disease is not known.
      METHODS: We reviewed all patients with bicuspid aortic valves undergoing aortic
      valve replacement at our institution from 1979 through 1993 (n = 201). Patients
      undergoing concomitant replacement of the ascending aorta were excluded. RESULTS:
      Follow-up was obtained on 98% of patients and was 10.3 +/- 3.8 (mean +/- SD)
      years. The average patient age was 56 +/- 15 years, and 76% were male. The
      ascending aorta was normal (<4.0 cm) in 115 (57%) patients, mildly dilated (4.0
      4.4 cm) in 64 (32%) patients, and moderately dilated (4.5-4.9 cm) in 22 (11%)
      patients. All patients with bicuspid aortic valves with marked dilation (>5.0 cm)
      underwent replacement of the ascending aorta and were therefore excluded. Fifteen
      year survival was 67%. During follow-up, 44 patients required reoperation,
      predominantly for aortic valve prosthesis failure. Twenty-two patients had long
      term complications related to the ascending aorta: 18 required an operative
      procedure to replace the ascending aorta (for aortic aneurysm), 1 had aortic
      dissection, and 3 experienced sudden cardiac death. Fifteen-year freedom from
      ascending aorta-related complications was 86%, 81%, and 43% in patients with an
      aortic diameter of less than 4.0 cm, 4.0 to 4.4 cm, and 4.5 to 4.9 cm,
      respectively ( P < .001). CONCLUSIONS: Patients undergoing operations for
      bicuspid aortic valve disease should be considered for concomitant replacement of
      the ascending aorta if the diameter is 4.5 cm or greater.

PMID- 15514595
TI  - New approach to multiple ventricular septal defect closure with intraoperative
      echocardiography and double patches sandwiching the septum.
AB  - OBJECTIVE: This was an evaluation of a new approach to the management of multiple
      muscular ventricular septal defects. The defects were located with epicardial
      echocardiography, then transfixed with a guide wire inserted directly through the
      right ventricular free wall. They were closed with a custom-made multilayered
      double-patch device under cardioplegic arrest through a standard right atriotomy.
      METHODS: This was a retrospective study of 14 consecutive patients. RESULTS: The
      median age and body weight at repair were 40 days (range 1 week-8 years, 3
      months) and 4.1 kg (2.8-24 kg), respectively. Five patients (36%) had undergone
      at least one previous sternotomy; 11 patients (78%) had associated cardiac
      lesions. Closure of the multiple septal defects was successful in 12 patients
      (85%). Failure to localize all defects led to pulmonary artery banding in 2
      patients. One patient had the residual septal defect closed with a percutaneous
      device 6 months later, and in the second patient the residual defect was closed
      with a conventional approach 11 months afterward. Two patients had permanent
      pacemaker insertion. In 279 patient-months of follow-up, there was 1 cardiac
      arrest on day 1 and no early or late deaths; all children but one are free of
      cardiac medications, and no significant residual left-to-right shunts were
      demonstrated in any patient. CONCLUSION: The reported management of multiple
      ventricular septal defects has been successful in this series, even in neonates
      and infants with complex associated cardiac lesions. It appears safe, simple, and
      effective.

PMID- 15514596
TI  - Evidence of pulmonary vascular disease after heart transplantation for Fontan
      circulation failure.
AB  - OBJECTIVES: Elevated pulmonary vascular resistance may contribute to late Fontan
      circulation failure but is difficult to assess in such patients. Our aims were to
      assess outcomes of patients with failed Fontan circulation after heart
      transplantation and to determine whether elevated pulmonary vascular resistance
      might have contributed to the failure. METHODS: Fifteen patients (14 Fontan
      circulations, 1 Kawashima circulation) underwent transplantation. The most common
      indication was ventricular dysfunction (mean ventricular end-diastolic pressure
      12.5 mm Hg). Patients with early failures (n = 4) required transplantation less
      than 1 year after the Fontan operation. Those with late failures (n = 11)
      underwent transplantation at least 1 year after the Fontan operation. Mean age at
      transplantation was 11.6 years. Mean Fontan-transplantation interval was 7.4
      years. Mean pulmonary arterial pressure, transpulmonary gradient, and pulmonary
      vascular resistance before and after transplantation were assessed. Paired t
      tests of variable differences were used to compare variables. Survival was
      estimated by the Kaplan-Meier method. RESULTS: In-hospital mortality was 7%.
      There were 2 late events (1 death, 1 retransplantation) related to compliance or
      rejection issues. Graft survivals were 93%, 82%, and 82% at 3, 5, and 7 years,
      respectively. Posttransplantation pulmonary vascular resistance was elevated
      (>2.0 Wood units . m 2 ) in 11 of 14 survivors past initial hospitalization (mean
      3.3 +/- 1.7 Wood units . m 2 ). Only patients with early Fontan failures (3 of 4)
      had normal posttransplantation pulmonary vascular resistance. In paired
      comparisons, posttransplantation transpulmonary gradient was increased by a mean
      of 6.8 mm Hg ( P < .0001) relative to pretransplantation value. CONCLUSIONS:
      Outcomes after heart transplantation for failed Fontan circulation were good.
      Mild-to-moderate pulmonary vascular disease was evident after heart
      transplantation for late failure. Elevated pulmonary vascular resistance is a
      likely contributor to Fontan circulation failure.

PMID- 15514597
TI  - Outcomes of mitral valve replacement in children: a competing-risks analysis.
AB  - OBJECTIVE: We sought to define patient characteristics, outcomes, and associated
      factors after mitral valve replacement in children. METHODS: We included 104
      children undergoing at least one mitral valve replacement between 1980 and 2003
      and reviewed clinical records. Competing-risks methodology was used to determine
      time-related prevalence and associated risk factors after initial mitral valve
      replacement for death and repeat replacement. RESULTS: The underlying mitral
      valve disease was congenital in 83%, rheumatic in 13%, Marfan syndrome in 3%, and
      isolated endocarditis in 1%, with 64% having primarily regurgitation, 16% having
      stenosis, 20% having both, and 32% having undergone previous valvotomy,
      valvuloplasty, or repair. There were 137 valve replacements, with 26 patients
      having more than one. Valve prosthesis type was St Jude Medical in 37%, Bjork
      Shiley in 25%, Carbomedics in 20%, Ionescu-Shiley in 10%, and other types in 8%.
      Both early and late complications were common. Median age at the initial
      replacement was 5.9 years (range, birth to 19 years). Competing-risks analysis
      predicted 19% to have died at 15 years after initial replacement, with risk
      factors including noncongenital valve morphology, lower weight, and longer
      duration of cardiopulmonary bypass. A repeat replacement was predicted for 71%,
      with risk factors including the presence of multiple left-heart obstructive
      lesions and Ionescu-Shiley valve prosthesis. CONCLUSIONS: Mitral valve
      replacement might be necessary in children with extremely dysplastic valves and
      severe hemodynamic impairment or after failed repair. However, with the
      appropriate selection of the prosthetic valve and reduction of cardiopulmonary
      bypass time, surgeons might decrease mortality and increase prosthesis longevity.

PMID- 15514598
TI  - Left ventricular performance of pulmonary atresia with intact ventricular septum
      after right heart bypass surgery.
AB  - OBJECTIVE: The left ventricular performance in patients with pulmonary atresia
      with intact ventricular septum who were Fontan candidates before and after the
      bidirectional Glenn procedure and a staged total cavopulmonary connection was
      compared with that in patients with tricuspid atresia. METHODS: Contractility
      (end-systolic elastance), afterload (effective arterial elastance), and
      ventricular efficiency (ventriculoarterial coupling, arterial elastance/end
      systolic elastance ratio), and the ratio of stroke work and pressure-volume area
      were approximated on the basis of cardiac catheterization data before the
      bidirectional Glenn procedure, before and after staged total cavopulmonary
      connection, and approximately 1 year after the completion of total cavopulmonary
      connection in 20 patients with pulmonary atresia with intact ventricular septum
      and 21 patients with tricuspid atresia. RESULTS: The end-systolic elastance of
      the pulmonary atresia with intact ventricular septum group was significantly
      inferior to that of the tricuspid atresia group after bidirectional Glenn
      procedure and total cavopulmonary connection (1 year after total cavopulmonary
      connection 1.85 +/- 0.51 mm Hg . m 2 . mL -1 vs 2.84 +/- 0.96 mm Hg . m 2 . mL -1
      , P < .01). The arterial elastance was not different between groups throughout
      the assessment period and tended to increase in a stepwise fashion after
      bidirectional Glenn procedure and total cavopulmonary connection. The arterial
      elastance/end-systolic elastance ratio and ratio of stroke work and pressure
      volume area of the pulmonary atresia with intact ventricular septum group tended
      to worsen, whereas those of the tricuspid atresia group tended to improve. The
      difference reached statistical significance 1 year after total cavopulmonary
      connection (1.15 +/- 0.35 vs 0.82 +/- 0.23 and 64.2% +/- 6.7% vs 71.3% +/- 5.7%,
      respectively, P < .05 and P < .05, respectively). CONCLUSION: The contractility
      and ventricular efficiency of patients with pulmonary atresia with intact
      ventricular septum are inferior to those of patients with tricuspid atresia after
      bidirectional Glenn procedure and total cavopulmonary connection. A high-pressure
      residual right ventricle may impair the left ventricular performance of patients
      with pulmonary atresia with intact ventricular septum after bidirectional Glenn
      procedure and total cavopulmonary connection.

PMID- 15514599
TI  - Intraoperative and intermediate-term angiographic results of coronary artery
      bypass surgery with Symmetry proximal anastomotic device.
AB  - OBJECTIVE: The objective of this study was to investigate the patency in
      saphenous vein coronary bypass grafts in which the proximal anastomoses were
      performed with automatic connector devices or with a traditional suture
      technique. METHODS: Forty-six patients underwent coronary artery bypass grafting
      without cardiopulmonary bypass by using one thoracic graft and one or more
      saphenous vein grafts. Grafts were attached to the aorta with a Symmetry
      connector (St Jude Medical, Inc, St Paul, Minn) in 23 patients, and partial
      occlusion of the aorta and sutured anastomoses were used in 23 other patients.
      Grafts were studied intraoperatively with transit time flowmetry and angiography
      and revised if necessary. Angiography was repeated after 3 to 5 months. RESULTS:
      Intraoperative graft patency did not differ between the 2 groups. Follow-up
      angiography demonstrated excellent thoracic graft patency. Vein graft patency
      decreased to 50% in the Symmetry group, whereas it was 90% in the suture group (
      P = .01). Twenty-five percent of the Symmetry grafts had significant stenosis in
      the connector. CONCLUSION: Saphenous vein grafts anastomosed to aorta with the
      Symmetry proximal connector have low intermediate patency compared with those
      with traditionally sutured anastomoses. We do not recommend the routine use of
      this device in coronary artery bypass operations.

PMID- 15514601
TI  - Anastomotic complications after tracheal resection: prognostic factors and
      management.
AB  - OBJECTIVE: We sought to identify risk factors for anastomotic complications after
      tracheal resection and to describe the management of these patients. METHODS:
      This was a single-institution, retrospective review of 901 patients who underwent
      tracheal resection. RESULTS: The indications for tracheal resection were
      postintubation tracheal stenosis in 589 patients, tumor in 208, idiopathic
      laryngotracheal stenosis in 83, and tracheoesophageal fistula in 21. Anastomotic
      complications occurred in 81 patients (9%). Eleven patients (1%) died after
      operation, 6 of anastomotic complications and 5 of other causes (odds ratio 13.0,
      P = .0001 for risk of death after anastomotic complication). At the end of
      treatment, 853 patients (95%) had a good result, whereas 37 patients (4%) had an
      airway maintained by tracheostomy or T-tube. The treatments of patients with an
      anastomotic complication were as follows: multiple dilations (n = 2), temporary
      tracheostomy (n = 7), temporary T-tube (n = 16), permanent tracheostomy (n = 14),
      permanent T-tube (n = 20), and reoperation (n = 16). Stepwise multivariable
      analysis revealed the following predictors of anastomotic complications:
      reoperation (odds ratio 3.03, 95% confidence interval 1.69-5.43, P = .002),
      diabetes (odds ratio 3.32, 95% confidence interval 1.76-6.26, P = .002), lengthy
      (> or =4 cm) resections (odds ratio 2.01, 95% confidence interval 1.21-3.35, P =
      .007), laryngotracheal resection (odds ratio 1.80, 95% confidence interval 1.07
      3.01, P = .03), age 17 years or younger (odds ratio 2.26, 95% confidence interval
      1.09-4.68, P = .03), and need for tracheostomy before operation (odds ratio 1.79,
      95% confidence interval 1.03-3.14, P = .04). CONCLUSIONS: Tracheal resection is
      usually successful and has a low mortality. Anastomotic complications are
      uncommon, and important risk factors are reoperation, diabetes, lengthy
      resections, laryngotracheal resections, young age (pediatric patients), and the
      need for tracheostomy before operation.

PMID- 15514600
TI  - Superiority of early relative to late ischemic preconditioning in spinal cord
      protection after descending thoracic aortic occlusion.
AB  - OBJECTIVE: We previously showed that ischemic preconditioning significantly
      reduced spinal cord injury caused by 35-minute aortic occlusion. In this study we
      investigated the effect of ischemic preconditioning on spinal cord injury after
      45-minute aortic occlusion. METHODS: Thirty-two pigs were divided as follows:
      group 1 (n = 6) underwent sham operation, group 2 (n = 6) underwent 20 minutes of
      aortic occlusion, group 3 (n = 6) underwent 45 minutes of occlusion, group 4 (n =
      6) underwent 20 minutes of occlusion and 48 hours later underwent an additional
      45 minutes, and group 5 (n = 8) underwent 20 minutes of occlusion and 80 minutes
      later underwent an additional 45 minutes. Aortic occlusion was accomplished with
      two balloon occlusion catheters placed fluoroscopically after the origin of the
      left subclavian artery and at the aortic bifurcation. Neurologic evaluation was
      by Tarlov score. The lower thoracic and lumbar spinal cords were harvested at 120
      hours and examined histologically with hematoxylin-eosin staining. The number of
      neurons was counted, and the inflammation was scored (0-4). Statistical analysis
      was by Kruskal-Wallis and 1-way analysis of variance tests. RESULTS: Group 5
      (early ischemic preconditioning) had better Tarlov scores than group 3 ( P <
      .001) and group 4 (late ischemic preconditioning, P < .001). The histologic
      changes were proportional to the Tarlov scores, with the least histologic damage
      in the animals of group 5 relative to group 3 (number of neurons P < .001,
      inflammation P = .004) and group 4 (number of neurons P < .001, inflammation P =
      .006). CONCLUSION: Early ischemic preconditioning is superior to late ischemic
      preconditioning in reducing spinal cord injury caused by the extreme ischemia of
      45 minutes of descending thoracic aortic occlusion.

PMID- 15514602
TI  - Proteasome inhibition sensitizes non-small cell lung cancer to histone
      deacetylase inhibitor-induced apoptosis through the generation of reactive oxygen
      species.
AB  - OBJECTIVES: The histone deacetylase inhibitor suberoylanilide hydroxamic acid
      induces apoptosis in some malignancies through mitochondrial injury and
      generation of reactive oxygen species. Histone deacetylase inhibitors also
      activate the antiapoptotic transcription factor nuclear factor kappaB. We
      hypothesize that proteasome inhibition with bortezomib (Velcade; Millennium
      Pharmaceuticals, Inc, Cambridge, Mass)will inhibit nuclear factor kappaB
      activation, enhance suberoylanilide hydroxamic acid-induced mitochondrial injury,
      and sensitize non-small cell lung cancer cells to apoptosis. METHODS: Four
      tumorigenic non-small cell lung cancer cell lines were treated with nothing,
      suberoylanilide hydroxamic acid, bortezomib, or both drugs. Nuclear factor kappaB
      dependent transcription was determined by reporter gene assays and endogenous
      interleukin 8 transcription. Reactive oxygen species were quantified by using the
      fluorophore H 2 DCFDA. Cell viability was determined on the basis of clonogenic
      survival, and apoptosis was measured by quantifying caspase-3 activity and DNA
      fragmentation. Apoptosis and cell-survival assays were repeated in similarly
      treated cells incubated in the presence or absence of N-acetyl cysteine.
      Statistical significance was determined by means of analysis of variance.
      RESULTS: Suberoylanilide hydroxamic acid significantly enhanced interleukin 8 and
      nuclear factor kappaB-dependent reporter gene transcription, and these effects
      were inhibited by bortezomib ( P < or = .01). Combined treatment with
      suberoylanilide hydroxamic acid and bortezomib induced greater reactive oxygen
      species generation, more apoptosis ( P < or = .02), and more cell death ( P < or
      = .001) than either drug alone. N-acetyl cysteine diminished the induction of
      apoptosis and enhanced cell survival ( P < or = .04). CONCLUSIONS:
      Suberoylanilide hydroxamic acid and bortezomib synergistically induce reactive
      oxygen species generation in non-small cell lung cancer, and this plays a
      critical role in the induction of apoptosis after treatment. Combined treatment
      with suberoylanilide hydroxamic acid and bortezomib might be an effective
      treatment strategy for non-small cell lung cancer.

PMID- 15514603
TI  - Is coma an absolute contraindication for emergency central aortic operation?

PMID- 15514604
TI  - Surgical management of a giant left main coronary artery aneurysm.

PMID- 15514605
TI  - Valve-sparing root replacement for pulmonary autograft dissection late after the
      Ross operation.

PMID- 15514606
TI  - Metastatic left atrial synovial sarcoma mimicking a myxoma.

PMID- 15514607
TI  - Aortic valve repair for quadricuspid aortic valve associated with aortic
      regurgitation and ascending aortic aneurysm.

PMID- 15514608
TI  - Sarcoidosis of the aortic root.

PMID- 15514609
TI  - Failure of medical therapy for pulmonary "thromboembolic" disease: beware the
      unsuspected primary sarcoma of the pulmonary artery.

PMID- 15514610
TI  - Surgical repair of a leaking double postinfarction left ventricular
      pseudoaneurysm.

PMID- 15514611
TI  - Atrial septal mass: transesophageal echocardiographic assessment.

PMID- 15514612
TI  - Fatal right ventricular infarction caused by Bioglue coronary embolism.

PMID- 15514613
TI  - A technique for repair of mitral paravalvular leak.

PMID- 15514614
TI  - Surgical management of progression to type A dissection from an intramural
      hematoma previously treated with endovascular stent graft placement.

PMID- 15514615
TI  - Pressure criterion for placement of distal perfusion catheter to prevent limb
      ischemia during adult extracorporeal life support.

PMID- 15514616
TI  - A rare case of extralobar sequestration with hemoptysis.

PMID- 15514617
TI  - Tracheal obstruction from mediastinal arteriovenous malformation.

PMID- 15514618
TI  - Bronchotomy in the treatment of a low-grade bronchial mucoepidermoid carcinoma in
      a child.

PMID- 15514619
TI  - Endovascular coil embolization for acute management of traumatic pulmonary artery
      pseudoaneurysm.

PMID- 15514620
TI  - Giant superior mediastinal angioleiomyoma.

PMID- 15514621
TI  - Tracheobronchial amyloidosis: a surgical disease with long-term consequences.

PMID- 15514622
TI  - Beta-blocker prevented repeated pulmonary hypertension episodes after bilateral
      lung transplantation in a patient with primary pulmonary hypertension.

PMID- 15514623
TI  - Carpentier-Edwards Perimount valve and intraoperative structural failure.

PMID- 15514624
TI  - Moderate mitral regurgitation repair at the time of coronary bypass: when is it
      required?

PMID- 15514625
TI  - Guidelines for coronary revascularization revisited? A note of caution.

PMID- 15514626
TI  - Repair of the Ebstein anomaly.

PMID- 15514627
TI  - The difference is meaningful: anatomic coronary-coronary bypass or physiologic
      coronary-coronary bypass?

PMID- 15514628
TI  - Pleural effusion and off-pump Fontan procedure.

PMID- 15514629
TI  - Thymic neuroendocrine carcinoma (carcinoid): what if octreotide scanning is
      negative?

PMID- 15514630
TI  - Introduction. Quality of health care.

PMID- 15514631
TI  - NRMI and current treatment patterns for ST-elevation myocardial infarction.
AB  - The National Registry of Myocardial Infarction (NRMI) is one of the oldest and
      largest registries of acute myocardial infarction (AMI). Since 1990, 4 NRMI
      studies have been launched, one of which is ongoing (Table I). In all, 1600
      hospitals have participated and >2.2 million patients have been followed. This
      paper highlights some of our discoveries pertaining to ST-segment elevation and
      subsequent contributions to patient care.

PMID- 15514632
TI  - Care of non-ST-segment elevation patients: insights from the CRUSADE national
      quality improvement initiative.
AB  - Acute coronary syndromes (ACS), including non-ST-segment elevation (NSTE) ACS,
      represent a significant source of morbidity and mortality in the United States.
      To address this widespread, serious health problem, the American College of
      Cardiology and the American Heart Association (ACC/AHA) published guidelines for
      the treatment of NSTE ACS, which include unstable angina (UA) and NSTE myocardial
      infarction (NSTEMI). These ACC/AHA guidelines are intended to help physicians
      make appropriate decisions when diagnosing and treating patients with NSTE ACS.

PMID- 15514633
TI  - An international perspective on acute coronary syndrome care: insights from the
      Global Registry of Acute Coronary Events.
AB  - Management of acute coronary syndromes (ACS) involves a series of diagnostic and
      therapeutic decisions and can include a variety of invasive and noninvasive
      interventions. The potential risks and benefits of these interventions,
      especially in specific patient populations, remain uncertain. The purpose of the
      Global Registry of Acute Coronary Events (GRACE) is to gather data about the
      management and outcome of ACS in a robust, multinational population and to use
      these data to improve the care and management of patients with ACS.

PMID- 15514634
TI  - The American Heart Association Get With The Guidelines program.
AB  - Get With The Guidelines (GWTG) is a hospital-based quality improvement initiative
      created by the American Heart Association (AHA) and the American Stroke
      Association (ASA) to improve the care of patients with cardiac diseases and
      stroke. It supports the AHA mission to reduce death and disability due to
      cardiovascular diseases and stroke. It is evidence-based and founded on the
      American College of Cardiology/American Heart Association Guidelines for
      secondary prevention of cardiovascular diseases and is designed to help health
      care providers consistently treat patients in accordance with these accepted
      guidelines.

PMID- 15514635
TI  - Taking the ACC/AHA guidelines for care of Acute Myocardial Infarction to the
      bedside: the GAP projects in southeastern Michigan.

PMID- 15514636
TI  - Success stories: how hospitals are improving care.
AB  - What does it take to make changes in practice and sustain those changes over
      time? This paper describes 3 successful attempts to improve the quality of care
      at US hospitals participating in the CRUSADE (Can Rapid risk stratification of
      Unstable angina patients Suppress ADverse outcomes with Early implementation of
      the American College of Cardiology [ACC]/American Heart Association [AHA]
      Guidelines), the Guidelines Applied in Practice (GAP), and the Get With The
      Guidelines (GWTG) programs. Techniques that work at the local level and practical
      tips that can be adopted to develop quality improvement (QI) initiatives are
      highlighted.

PMID- 15514637
TI  - Should we link payment to quality?
AB  - The movement to improve the quality of medical care is accelerating as payers and
      patients demand greater accountability. Recently, the Center for Medicare and
      Medicaid Services (CMS) increased the quality assessment stakes even further with
      a proposal to link hospitals' reimbursement rates to their "performance" on
      specific quality-of-care indicators. While many clinicians would generally agree
      with the concept that providing better medical care should be rewarded, putting
      the idea into practice poses a challenge.

PMID- 15514638
TI  - A new small-bodied hominin from the Late Pleistocene of Flores, Indonesia.
AB  - Currently, it is widely accepted that only one hominin genus, Homo, was present
      in Pleistocene Asia, represented by two species, Homo erectus and Homo sapiens.
      Both species are characterized by greater brain size, increased body height and
      smaller teeth relative to Pliocene Australopithecus in Africa. Here we report the
      discovery, from the Late Pleistocene of Flores, Indonesia, of an adult hominin
      with stature and endocranial volume approximating 1 m and 380 cm3, respectively-
      equal to the smallest-known australopithecines. The combination of primitive and
      derived features assigns this hominin to a new species, Homo floresiensis. The
      most likely explanation for its existence on Flores is long-term isolation, with
      subsequent endemic dwarfing, of an ancestral H. erectus population. Importantly,
      H. floresiensis shows that the genus Homo is morphologically more varied and
      flexible in its adaptive responses than previously thought.

PMID- 15514639
TI  - Risky business.

PMID- 15514646
TI  - USDA encourages humane slaughter of animals.

PMID- 15514647
TI  - IACUC replacement parts: what are the requirements? No authority.

PMID- 15514648
TI  - IACUC replacement parts: what are the requirements?

PMID- 15514649
TI  - IACUC replacement parts: what are the requirements? Bad choices.

PMID- 15514650
TI  - IACUC replacement parts: what are the requirements? Inappropriate actions.

PMID- 15514651
TI  - Parenting in owl monkeys (Aotus spp.).

PMID- 15514653
TI  - Laboratory animal allergies: overview of causation and prevention.
AB  - In sensitized individuals, exposure to laboratory animal allergens can cause
      symptoms ranging in severity from annoying to life-threatening. The author
      presents an overview of the pathology of LAA and discusses a number of methods
      that can be used to limit exposure to these allergens.

PMID- 15514654
TI  - Moving on up: upgrading from an ABSL2 to ABSL3 facility.
AB  - Renewed interest in bioterrorism-related research has resulted in the need for
      more ABSL3/4 facilities. In some cases, money has been available to build new
      facilities, but more often institutions are faced with retrofitting existing
      facilities to meet the higher containment standards. The author discusses several
      factors that must be addressed before beginning this type of renovation project.

PMID- 15514655
TI  - Microbiological monitoring in individually ventilated cage systems.
AB  - Housing rodents in IVC racks has many advantages over conventional cages but also
      presents unique challenges related to health monitoring. The authors review the
      issues to consider in design of a sentinel program using IVC systems.

PMID- 15514656
TI  - Separated at birth.

PMID- 15514657
TI  - Genomic Control to the extreme.

PMID- 15514659
TI  - A note of caution on the Knockout Mouse Project.

PMID- 15514662
TI  - RNA interference on chromosomes.

PMID- 15514660
TI  - The Collaborative Cross, a community resource for the genetic analysis of complex
      traits.
AB  - The goal of the Complex Trait Consortium is to promote the development of
      resources that can be used to understand, treat and ultimately prevent pervasive
      human diseases. Existing and proposed mouse resources that are optimized to study
      the actions of isolated genetic loci on a fixed background are less effective for
      studying intact polygenic networks and interactions among genes, environments,
      pathogens and other factors. The Collaborative Cross will provide a common
      reference panel specifically designed for the integrative analysis of complex
      systems and will change the way we approach human health and disease.

PMID- 15514663
TI  - A new gene on the X involved in Fanconi anemia.

PMID- 15514664
TI  - From spindle checkpoint to cancer.

PMID- 15514665
TI  - Complementing complexity.

PMID- 15514666
TI  - Gangliosides help stabilize the brain.

PMID- 15514669
TI  - Lifespan and mitochondrial control of neurodegeneration.
AB  - We examine the allometric (comparative scaling) relationships between rates of
      neurodegeneration resulting from equivalent mutations in a diverse group of genes
      from five mammalian species with different maximum lifespan potentials. In both
      retina and brain, rates of neurodegeneration vary by as much as two orders of
      magnitude and are strongly correlated with maximum lifespan potential and rates
      of formation of mitochondrial reactive oxygen and nitrogen species (RONS). Cell
      death in these disorders is directly or indirectly regulated by the intrinsic
      mitochondrial cell death pathway. Mitochondria are the main source of RONS
      production and integrate cellular stress signals to coordinate the intrinsic
      pathway. We propose that these two functions are intimately related and that
      steady-state RONS-mediated signaling or damage to the mitochondrial stress
      integration machinery is the principal factor setting the probability of cell
      death in response to a diverse range of cellular stressors. This provides a new
      and unifying framework for investigating neurodegenerative disorders.

PMID- 15514674
TI  - TRAIL and thymocyte apoptosis: not so deadly?

PMID- 15514675
TI  - Loss of TRAIL-R does not affect thymic or intestinal tumor development in p53 and
      adenomatous polyposis coli mutant mice.

PMID- 15514676
TI  - Cytotoxic necrotizing factor 1 hinders skeletal muscle differentiation in vitro
      by perturbing the activation/deactivation balance of Rho GTPases.
AB  - The current knowledge assigns a crucial role to the Rho GTPases family (Rho, Rac,
      Cdc42) in the complex transductive pathway leading to skeletal muscle cell
      differentiation. Their exact function in myogenesis, however, remains largely
      undefined. The protein toxin CNF1 was herein employed as a tool to activate Rho,
      Rac and Cdc42 in the myogenic cell line C2C12. We demonstrated that CNF1 impaired
      myogenesis by affecting the muscle regulatory factors MyoD and myogenin and the
      structural protein MHC expressions. This was principally driven by Rac/Cdc42
      activation whereas Rho apparently controlled only the fusion process. More
      importantly, we proved that a controlled balance between Rho and Rac/Cdc42
      activation/deactivation state was crucial for the correct execution of the
      differentiation program, thus providing a novel view for the role of Rho GTPases
      in muscle cell differentiation. Also, the use of Rho hijacking toxins can
      represent a new strategy to pharmacologically influence the differentiative
      process.

PMID- 15514677
TI  - A cellular machine generating apoptosis-prone aneuploid cells.

PMID- 15514678
TI  - A Drosophila p38 orthologue is required for environmental stress responses.
AB  - The p38 mitogen-activated protein kinase (MAPK) cascade is an evolutionarily
      conserved signalling mechanism involved in processes as diverse as apoptosis,
      cell fate determination, immune function and stress response. Aberrant p38
      signalling has been implicated in many human diseases, including heart disease,
      cancer, arthritis and neurodegenerative diseases. To further understand the role
      of p38 in these processes, we generated a Drosophila strain that is null for the
      D-p38a gene. Mutants are homozygous viable and show no observable developmental
      defects. However, flies lacking D-p38a are susceptible to some environmental
      stresses, including heat shock, oxidative stress and starvation. These phenotypes
      only partially overlap those caused by mutations in D-MEKK1 and dTAK1, suggesting
      that the D-p38a gene is required to mediate some, but not all, of the functions
      ascribed to p38 signalling.

PMID- 15514679
TI  - Dynamic interactions of a transcription factor with DNA are accelerated by a
      chromatin remodeller.
AB  - Most components in the nucleus are in a state of dynamic equilibrium maintained
      by the rapid mobility of nuclear proteins within and between compartments.
      Mobility is believed to reflect transient binding, but the identity of the
      binding sites and the function of the transient interactions are a matter of
      debate. Furthermore, we know little about how these processes may be regulated.
      Here, we investigate the nature and regulation of transcription factor binding
      and mobility in the nucleus of yeast cells. Using the Ace1p transcriptional
      activator, we show that nonspecific DNA binding interactions seem to have a role
      in retarding Ace1p nuclear mobility. Surprisingly, we find that this binding is a
      regulated process using a chromatin remodeller to speed up Ace1p interactions at
      nonspecific DNA sites. Our results suggest that transcription factor mobility
      represents a diffusion-driven, rapid sampling of nonspecific DNA sites, and that
      chromatin remodellers accelerate this genomic search process.

PMID- 15514680
TI  - Induction of apoptosis and activation of NF-kappaB by CD95 require different
      signalling thresholds.
AB  - Mutations in the death domain of the death receptor CD95 (APO-1/Fas) cause
      lymphoproliferation and autoimmune disease in both lpr(cg) mice and in patients
      with autoimmune lymphoproliferative syndrome (ALPS) type Ia. By testing
      lymphocytes from ALPS type Ia patients, comparing heterozygous with homozygous
      lpr(cg) mice and coexpressing wild-type and mutant CD95 receptors, we demonstrate
      that induction of apoptosis requires two wild-type alleles of CD95. By contrast,
      nuclear factor-kappaB (NF-kappaB) can be fully activated in cells expressing both
      a mutant and a wild-type CD95 allele, suggesting different thresholds to activate
      the two signalling pathways. This was confirmed by testing lymphocytes from
      heterozygous lpr mice, which showed reduced sensitivity to CD95-mediated
      apoptosis but normal activation of NF-kappaB when compared with wild-type mice.
      Mutations in CD95 may eliminate the tumour-suppressive function of CD95, at the
      same time allowing induction of survival or proliferative pathways, which could
      contribute to the increased risk for lymphoma seen in ALPS type Ia patients.

PMID- 15514681
TI  - ZOMES III: the interface between signalling and proteolysis. Meeting on The COP9
      Signalosome, Proteasome and eIF3.

PMID- 15514684
TI  - In vitro efficacy of Fas ligand gene therapy for the treatment of bladder cancer.
AB  - Previous investigations have revealed that bladder cancer cells are generally
      resistant to Fas-mediated apoptosis by conventional Fas agonists. However, the
      ability of these cell lines to undergo Fas-mediated apoptosis may have been
      underappreciated. As a result, we investigated the in vitro efficacy of Fas
      ligand gene therapy for bladder cancer. Three human bladder cancer lines (T24,
      J82, and 5637) were treated with the conventional Fas agonist CH-11, a monoclonal
      antibody to the Fas receptor. Cells were also treated with a replication
      deficient adenovirus containing a modified murine Fas ligand gene fused to green
      fluorescent protein (GFP), AdGFPFasL. A virus containing the GFP gene alone was
      used to control for viral toxicity (AdGFP). Cell death was quantified using a
      tetrazolium-based (MTS) assay. Cells were also evaluated by Western blotting to
      evaluate poly (ADP-ribose) polymerase, caspase 8, and caspase 9 cleavage and by
      flow cytometry to determine the presence of coxsackie/adenovirus receptor (CAR).
      These studies confirmed bladder cancer resistance to cell death by the anti-Fas
      monoclonal antibody CH-11. This resistance was overcome with AdGFPFasL at a
      multiplicity of infection (MOI) of 1000 achieving over 80% cell death in all cell
      lines. Furthermore, greater than 80% cell death was evident in 5637 cells treated
      with low-dose AdGFPFasL (MOI=10). 5637 cells expressed significantly higher
      levels of surface CAR than J82 or T24 cells (P<.05). AdGFPFasL is cytotoxic to
      bladder cancer cells that would otherwise be considered Fas resistant, supporting
      its in vivo potential. Enhanced sensitivity to AdGFPFasL may be in part due to
      increased cell surface CAR levels.

PMID- 15514685
TI  - Tumor-specific intravenous gene delivery using oncolytic adenoviruses.
AB  - In this report, we describe a vector system that specifically delivers transgene
      products to tumors following intravenous (i.v.) administration. The Escherichia
      coli cytosine deaminase (CD) gene was placed in the E3B region of the tumor
      selective, replication-competent adenovirus ONYX-411, under the control of
      endogenous viral late gene regulatory elements. Thus, CD expression was directly
      coupled to the tumor-selective replication of the viral vector. In vitro, CD was
      expressed efficiently in various human cancer cell lines tested but not in
      cultured normal human cells, including human hepatocytes. Following i.v.
      administration into nude mice carrying human tumor xenografts, robust CD activity
      was detected only in tumors but not in liver or other normal tissues. Levels of
      CD activity in the tumors increased progressively following i.v. virus
      administration, correlating closely with virus replication in vivo. Subsequent
      administration of 5-fluorocytosine (5-FC) demonstrated a trend to improve the
      antitumor efficacy of these viruses in a mouse xenograft model, presumably due to
      the intratumoral conversion of 5-FC to the chemotherapeutic drug 5-fluorouracil.
      We show that the combination of a highly selective oncolytic virus, ONYX-411,
      with the strategic use of the viral E3B region for transgene insertion provides a
      powerful platform that allows for tumor-specific, persistent and robust transgene
      expression after i.v. administration. This technology provides an opportunity to
      enhance greatly both safety and efficacy of cancer gene therapy.

PMID- 15514686
TI  - "Doctor, I'm Putting on the Grail"

PMID- 15514687
TI  - Neuroleptic Malignant Syndrome: A Primary Care Perspective.
AB  - In recent years, there has been an increased use of neuroleptic agents in the
      primary care setting. Neuroleptic malignant syndrome (NMS) is a rare complication
      of neuroleptic therapy that can be missed if not suspected. This manuscript
      reviews the diagnosis and management of NMS in the primary care setting. There is
      a lack of prospective data, and most of the information is obtained from case
      series. Physicians need to have a high index of suspicion with regard to
      excluding NMS in patients taking neuroleptics and presenting with hyperthermia.

PMID- 15514688
TI  - A Somatoform Variant of Obsessive-Compulsive Disorder: A Case Report of OCD
      Presenting With Persistent Vomiting.
AB  - Acute nausea and vomiting are often self-limited or easily treated. Persistent
      vomiting, however, poses diagnostic and therapeutic challenges for the primary
      care physician. In addition to gastrointestinal, neurologic, and endocrine
      disorders, the differential diagnosis includes psychiatric illnesses, such as
      eating and factitious disorders. We present the case of a 52-year-old woman
      referred to the Tulane University Internal Medicine/Psychiatry clinic with
      persistent daily vomiting for 8 years despite repeated medical evaluations. The
      vomiting was of sufficient severity to require intensive care unit admission for
      hematemesis. A dually trained internal medicine-psychiatry house officer obtained
      further history and identified that the woman experienced an intrusive thought
      that urged her to vomit after each meal. Resisting the urge resulted in
      intolerable anxiety that was relieved only by vomiting. Obsessive-compulsive
      disorder (OCD) was diagnosed according to DSM-IV criteria. Initiation of
      escitalopram with titration to clinical response resulted in full symptom
      resolution and meaningful quality of life improvement. Pertinent literature was
      reviewed using 2 methods: (1) an English-language MEDLINE search (1966-February
      2004) using the search terms vomiting and (chronicor psychogenicor psychiatric),
      and obsessive-compulsive disorder and (primary care or treatment); and (2) a
      direct search of reference lists of pertinent journal articles. A review of
      psychiatric etiologies of vomiting and primary care aspects of OCD is presented.
      Primary care clinicians are strongly encouraged to consider psychiatric
      etiologies, including OCD, when common symptoms persist or present in atypical
      ways. Such disorders can be debilitating but also responsive to treatment.

PMID- 15514689
TI  - Retrospective Study of Olanzapine in Depressive and Anxious States in Primary
      Care.
AB  - CONTEXT: Bipolar spectrum and treatment-resistant unipolar mood disorders are
      increasingly identified in primary care settings. Olanzapine demonstrates
      efficacy in the treatment of acute mania and bipolar depression and in bipolar
      maintenance therapy. Olanzapine-fluoxetine combination therapy shows efficacy in
      treatment-resistant depression. OBJECTIVE: To examine the efficacy and
      tolerability profile of olanzapine in various difficult-to-treat depressive
      and/or anxious states in primary care outpatients. METHOD: A retrospective chart
      review was conducted for all identifiable patients prescribed olanzapine for mood
      disorders (DSM-IV) during a 3-year period (July 1998-July 2001), utilizing
      clinician and nurse recall, sampling of general continuity clinic records, and a
      hand search of mood disorder clinic records. MAIN AND SECONDARY OUTCOME MEASURES:
      Initial and final scores on the Global Assessment of Functioning (GAF) scale,
      duration of therapy, and adverse effects. RESULTS: Thirty-seven patients were
      identified as having received treatment with olanzapine; 3 were referred to the
      mental health specialty sector at the time of treatment initiation, and 2 were
      lost to follow-up. Of the 32 patients receiving ongoing treatment by primary care
      clinicians, most were female (N = 23; 72%) and all were white (100%). Most were
      diagnosed with a mental illness in the bipolar spectrum (N = 25; 78%) and
      demonstrated treatment resistance with antidepressants and/or mood stabilizers
      (mean number of previous psychotropic medications = 3.7). In the group completing
      therapy (24 patients [75%]; mean duration of treatment = 242 days), GAF scores
      demonstrated a clinically and statistically significant improvement (mean initial
      GAF score = 59 +/- 9; mean final GAF score = 76 +/- 11; p < .0001). Twenty (83%)
      of these 24 patients demonstrated sustained improvement in their GAF scores. In
      the group that discontinued therapy (8 patients [25%]; mean duration of treatment
      = 123 days), GAF scores also demonstrated a clinically and statistically
      significant improvement (mean initial GAF score = 51 +/- 15; mean final GAF score
      = 70 +/- 11; p < .0001). Six (75%) of these 8 patients demonstrated sustained
      improvement in their GAF scores. For all patients, observed adverse effects
      included weight gain (25 patients [86%]; mean = 3.63 kg), sedation (6 patients
      [19%]), and dry mouth (1 patient [3%]). CONCLUSION: Olanzapine shows promise as
      an effective pharmacotherapeutic agent for primary care patients with mood
      disorders that lie along the bipolar spectrum or that are resistant to treatment
      with antidepressant monotherapies, but is associated with mild-to-moderate weight
      gain.

PMID- 15514691
TI  - The Cuban American With Depression in Primary Care.

PMID- 15514692
TI  - All Stressed Out.

PMID- 15514690
TI  - Sleepiness Versus Sleeplessness: Shift Work and Sleep Disorders in the Primary
      Care Setting.
AB  - This Academic Highlights section of The Primary Care Companion to The Journal of
      Clinical Psychiatry presents the highlights of the teleconference series
      "Differential Diagnosis and Management of Excessive Sleepiness," held April 5, 7,
      and 22, 2004. The teleconference and this ACADEMIC HIGHLIGHTS were supported by
      an unrestricted educational grant from Cephalon, Inc. This report was prepared by
      Physicians Postgraduate Press, Inc.

PMID- 15514693
TI  - I've Been Reading.

PMID- 15514694
TI  - A Case of Rhabdomyolysis After Intravenous Heroin Use.

PMID- 15514696
TI  - Dr. Glick Replies.

PMID- 15514695
TI  - Management of Bipolar Disorder in Primary Care Versus Psychiatric Settings.

PMID- 15514697
TI  - National Athletic Trainers' Association Position Statement: Management of Sport
      Related Concussion.

PMID- 15514698
TI  - A method for rapidly screening functionality of actin mutants and tagged actins.
AB  - Recombinant production and biochemical analysis of actin mutants has been
      hampered by the fact that actin has an absolute requirement for the eukaryotic
      chaperone CCT to reach its native state. We therefore have developed a method to
      rapidly screen the folding capacity and functionality of actin variants, by
      combining in vitro expression of labelled actin with analysis on native gels,
      band shift assays or copolymerization tests. Additionally, we monitor, using
      immuno-fluorescence, incorporation of actin variants in cytoskeletal structures
      in transfected cells. We illustrate the method by two examples. In one we show
      that tagged versions of actin do not always behave native-like and in the other
      we study some of the molecular defects of three beta-actin mutants that have been
      associated with diseases.

PMID- 15514699
TI  - The Use of Antisense Oligonucleotides in Evaluating Survivin as a Therapeutic
      Target for Radiation Sensitization in Lung Cancer.
AB  - Elucidating the mechanism of over and under expression of proteins is critical in
      developing a better understanding of cancer. Multiple techniques are used to
      examine differential expression of proteins in cells and assess changes in
      protein expression in response to therapies such as radiation. Reduced expression
      can be caused by protein inactivation, mRNA instability, or reduced
      transcription. The following protocol was used to determine the mechanism for the
      reduced expression of an antiapoptotic factor, survivin, in normal tissues in
      response to radiation and the defect in cancer cells that prevents this
      reduction. We also examined ways to overcome survivin over expression in cancer
      cells in order to sensitize them to radiation. We will focus on the use of
      antisense oligonucleotides, cell cycle analysis, and luciferase reporter genes.

PMID- 15514700
TI  - Serial block-face scanning electron microscopy to reconstruct three-dimensional
      tissue nanostructure.
AB  - Three-dimensional (3D) structural information on many length scales is of central
      importance in biological research. Excellent methods exist to obtain structures
      of molecules at atomic, organelles at electron microscopic, and tissue at light
      microscopic resolution. A gap exists, however, when 3D tissue structure needs to
      be reconstructed over hundreds of micrometers with a resolution sufficient to
      follow the thinnest cellular processes and to identify small organelles such as
      synaptic vesicles. Such 3D data are, however, essential to understand cellular
      networks that, particularly in the nervous system, need to be completely
      reconstructed throughout a substantial spatial volume. Here we demonstrate that
      datasets meeting these requirements can be obtained by automated block-face
      imaging combined with serial sectioning inside the chamber of a scanning electron
      microscope. Backscattering contrast is used to visualize the heavy-metal staining
      of tissue prepared using techniques that are routine for transmission electron
      microscopy. Low-vacuum (20-60 Pa H(2)O) conditions prevent charging of the
      uncoated block face. The resolution is sufficient to trace even the thinnest
      axons and to identify synapses. Stacks of several hundred sections, 50-70 nm
      thick, have been obtained at a lateral position jitter of typically under 10 nm.
      This opens the possibility of automatically obtaining the electron-microscope
      level 3D datasets needed to completely reconstruct the connectivity of neuronal
      circuits.

PMID- 15514701
TI  - Vascular NAD(P)H oxidase as a novel therapeutic target in vascular disease.
AB  - Oxidative stress, involving elevated levels of reactive oxygen species such as
      superoxide and peroxynitrite, has been implicated in the pathogenesis of several,
      if not most, forms of cardiovascular disease. Recent studies using viral-mediated
      gene transfer of genes that redress oxidative stress in animal models of
      cardiovascular disease have suggested that targeting sources of superoxide would
      provide a novel therapeutic strategy in cardiovascular disease. Identification of
      a vascular form of the NAD(P)H oxidase as the major source of superoxide has
      resulted in a search for effective inhibitors. This review summarizes the
      developments in the area of vascular NAD(P)H oxidase as a novel therapeutic
      target in vascular disease.

PMID- 15514702
TI  - Interaction of BDNF/TrkB signaling with NMDA receptor in learning and memory.
AB  - Brain-derived neurotrophic factor (BDNF) and its receptor TrkB play important
      roles in learning and memory. Memory acquisition is associated with an increase
      in BDNF mRNA and TrkB activation in specific brain areas. Pharmacologic and
      genetic deprivation of BDNF or TrkB results in an impairment of memory.
      Activation of the mitogen-associated protein kinase and phosphatidylinositol 3
      kinase signaling pathways is involved in BDNF-dependent learning and memory. A
      frequent single nucleotide polymorphism in the targeting region of the human BDNF
      gene (val66met) is associated with poorer episodic memory and abnormal
      hippocampal neuronal function in humans. The interaction of BDNF/TrkB signaling
      with N-methyl-D-aspartate receptors is important for spatial learning and memory,
      and an Src-family tyrosine kinase Fyn may play a key role in this interaction by
      linking TrkB with NR2B.

PMID- 15514703
TI  - Biological effects of C1 inhibitor.
AB  - C1 inhibitor is a serine proteinase inhibitor (serpin) that regulates activation
      of both the complement and contact systems. Regulation of complement system
      activation takes place through inactivation of the classical pathway proteases,
      C1r and C1s, the lectin pathway protease, MASP2, and perhaps via inhibition of
      alternative pathway activation by reversible binding to C3b. Regulation of
      contact system activation takes place through inactivation of plasma kallikrein
      and coagulation factor XIIa. Deficiency of C1 inhibitor results in hereditary
      angioedema, which is characterized by recurrent episodes of localized angioedema
      of the skin, gastrointestinal mucosa or upper respiratory mucosa. A variety of
      clinical, in vitro and animal experiments indicate that the mediator of increased
      vascular permeability in hereditary angioedema is bradykinin. Animal models
      suggest that in addition to its utility in therapy of hereditary angioedema, C1
      inhibitor may prove useful in a variety of other diseases including septic shock,
      reperfusion injury, hyperacute transplant rejection, traumatic and hemorrhagic
      shock, and the increased vascular permeability associated with thermal injury,
      interleukin-2 therapy and cardiopulmonary bypass. The therapeutic effect in these
      disease models very likely results from a combination of complement system
      activation, contact system activation and perhaps from other activities of C1
      inhibitor. These other activities include a direct interaction with endotoxin,
      which may help to prevent endotoxic shock and an interaction with selectin
      molecules on endothelial cells, which may serve both to concentrate C1 inhibitor
      at sites of inflammation and to inhibit the transmigration of leukocytes across
      the endothelium.

PMID- 15514704
TI  - Oxidative stress and the JNK pathway as a potential therapeutic target for
      diabetes.
AB  - Oxidative stress is produced under diabetic conditions and is likely involved in
      progression of pancreatic beta-cell dysfunction found in diabetes. Possibly due
      to low levels of antioxidant enzyme expressions, beta-cells are vulnerable to
      oxidative stress. When beta-cell-derived cell lines or isolated rat islets were
      exposed to oxidative stress, insulin gene expression was markedly decreased.
      Furthermore, when diabetic C57BL/ KsJ-db/db mice were treated with antioxidants,
      glucose tolerance was ameliorated. Histological analyses of the pancreata
      revealed that the beta-cell mass is significantly larger in the mice treated with
      the antioxidants. The antioxidant treatment also preserved the amounts of insulin
      content and insulin mRNA. As a possible mechanism underlying the phenomena,
      expression of pancreatic and duodenal homeobox factor-1 (PDX-1), an important
      transcription factor for the insulin gene, was more clearly visible in the nuclei
      of islet cells after the antioxidant treatment. Furthermore, oxidative stress
      induces nucleocytoplasmic translocation of PDX-1 through activation of the c-Jun
      N-terminal kinase (JNK) pathway, which leads to suppression of insulin gene
      expression. Taken together, oxidative stress and consequent activation of the JNK
      pathway are involved in progression of beta-cell dysfunction found in diabetes,
      and thus are a therapeutic target for diabetes.

PMID- 15514705
TI  - Molecule of the month. Oleoyl estrone.

PMID- 15514706
TI  - Advances in the combination of radiation therapy and chemotherapy against cancer.
AB  - From June 5 through June 8, 2004, the American Society of Clinical Oncology held
      its 45th Annual Meeting in New Orleans, Louisiana, USA. The meeting was devoted
      to the presentation of advances in management of malignant diseases with a
      variety of therapeutic modalities. The meeting brings together investigators,
      clinicians, policy makers and professionals interested in the science and impact
      of novel treatments on cancerous disease. This report will examine the advances
      in combined modality approaches (i.e., the use of radiation therapy and
      chemotherapy) for the treatment of malignant disease. This review will summarize
      the advances reported in the use of chemoradiation for sarcomas and tumors of the
      genitourinary tract, brain, gastrointestinal tract, breast and lung.

PMID- 15514707
TI  - Advances in the understanding of diabetes mellitus.
AB  - The American Diabetic Association held its 64th Scientific Sessions on June 4-8,
      2004, in Orlando, Florida, USA. The meeting was devoted to developments in
      different areas of diabetes mellitus research: epidemiology; understanding of
      diabetic microvascular and macrovascular complications; various modes of
      treatment including complementary and alternative medicine; new targets in the
      treatment of the disease, including islet cell transplantation; and the approach
      to the concept of good quality of care.

PMID- 15514708
TI  - Effect of peptide Pro-Gly-Pro on stress-induced behavioral changes in rats.
AB  - Tripeptide PGP in a dose of 1 mg/kg had a correcting effect on behavioral
      disorders in rats induced by stress exposure (forced swimming). PGP prevented the
      increase in anxiety and decrease in orientation and exploratory activity. Our
      results suggest that the effect of this peptide is realized via central nervous
      structures involved in organism's response to stress factors.

PMID- 15514709
TI  - Relationship between protein deficiency in the ration of rats during early
      ontogeny and function of enzyme systems of digestive and non-digestive organs in
      adult life.
AB  - Low protein content in the ration of rat pups during transfer from mixed to
      definitive nutrition (days 21-30 of life) has a negative impact on digestive
      function of the small intestine and trophic and barrier functions of the large
      intestine, liver, and kidneys and increases (sucrase, glycyl-L-leucin
      dipeptidase) or decreases (alkaline phosphatase, aminopeptidase M, glycyl-L
      leucine dipeptidase) enzyme activities in these organs in 6-month-old rats.
      Protein deficiency during the early ontogeny modulates functioning of the enzyme
      systems in digestive and non-digestive organs in adult life, which can lead to
      the development of not only gastrointestinal, but other visceral diseases.

PMID- 15514710
TI  - Effect of acute hypoxia in pregnant females on contractile activity of lymphatic
      vessels in the offspring.
AB  - Delayed consequences of acute hypoxia were studied in 60-day-old rat pups. The
      animals were exposed to acute hypobaric hypoxia on day 10 of embryogenesis. The
      offspring of intact females served as the control. Reactivity of mesenteric
      lymphatic vessels to norepinephrine was studied by vital microscopy. The
      frequency and duration of lymphatic vessel contractions in males significantly
      increased compared to the control. In females the duration of norepinephrine
      induced lymphatic vessel contractions increased, while the frequency and
      amplitude of contractions and basal vascular tone did not differ from the
      control.

PMID- 15514711
TI  - Lipid peroxidation in the brain and liver of rats during acute stress and
      melatonin treatment.
AB  - We studied the effects of acute stress and exogenous melatonin in various doses
      on the intensity of lipid peroxidation in emotiogenic structures of the brain and
      liver of rats with different activity in the open field. Stress had no effect on
      the content of malonic dialdehyde in the hypothalamus, sensorimotor cortex, and
      liver of active and passive rats receiving physiological saline. The influence of
      melatonin on malonic dialdehyde content depended on the dose of this substance.
      The amount of malonic dialdehyde in brain structures (active and passive rats)
      and liver (active rats) increased after administration of exogenous melatonin in
      doses of 0.5 and 2 mg/kg, but decreased after treatment with the hormone in a
      dose of 1 mg/kg. Melatonin in various doses decreased malonic dialdehyde content
      in the liver of passive rats. The effects of melatonin are partly related to
      modulation of lipid peroxidation in central and peripheral tissues of the
      organism.

PMID- 15514712
TI  - Changes in hemodynamics and respiration in rats with different resistance to
      acute hypoxia.
AB  - Effects of acute hypoxia on hemodynamics and respiration were studied in acute
      experiments on narcotized rats. The animals were divided into groups
      characterized by high, low-, and medium- resistance to hypoxia by the time of
      respiration arrest during inhalation of gas mixture containing 3% O2. Hemodynamic
      parameters of highly resistant animals were higher than in low-resistant rats
      throughout the entire hypoxic period. The development of a rare (with prolonged
      inspiratory phase) respiratory rhythm in highly resistant rats is an adaptive
      reaction, which allows them longer tolerate hypoxia compared to low-resistant
      animals.

PMID- 15514713
TI  - Tissue homeostasis of the myocardium in newborn albino rats exposed to
      intrauterine hypoxia.
AB  - Somatometric indexes were modified in the offspring of rats exposed to hypobaric
      hypoxia. DNA synthesis and tissue mitotic index increased in 5-day-old male rats,
      but underwent less pronounced changes in females. Our results indicate that
      hypoxia modulates morphogenesis of the myocardium. We revealed sex differences in
      the reaction of newborn albino rats to intrauterine hypoxia.

PMID- 15514714
TI  - Antioxidant status of erythrocytes after acupuncture treatment.
AB  - A course of acupuncture therapy in patients with locomotor, peripheral nervous
      system, gynecological, and bronchopulmonary diseases led to complete or partial
      normalization of nonspecifically changed MDA content, catalase and glutathione
      peroxidase activities in erythrocytes. SOD activity increased after therapy and
      did not differ from the control. Acupuncture stabilized disordered LPO processes
      and improved the antioxidant status of erythrocytes.

PMID- 15514715
TI  - Algorithm for evaluation of crystal figures obtained after drying of mixed
      saliva.
AB  - Algorithm of qualitative description of crystallographic aggregations of mixed
      saliva was developed. The efficiency of this method for the diagnosis of
      gastrointestinal diseases was demonstrated.

PMID- 15514716
TI  - Protein peroxidation in the plasma of prenatally stressed rats.
AB  - We studied the effect of prenatal stress on protein peroxidation in the plasma of
      rats during postnatal ontogeny. Oxidative destruction of proteins in prenatally
      stressed rats differed from that in control animals. These differences were most
      pronounced in postnatal ontogeny, i.e. during the development and maturation of
      CNS.

PMID- 15514717
TI  - Increase in serum concentration of FAS ligand as a possible mechanism for
      antithyroid cytotoxicity during autoimmune thyroid diseases.
AB  - We studied the dependence of serum cytotoxic activity on the contents of soluble
      apoptosis receptor and its soluble ligand in patients with autoimmune thyroid
      diseases.

PMID- 15514718
TI  - Potassium assay in blastomere of two-cell mouse embryo after equilibration and
      washing from cryoprotector.
AB  - The need for effective methods of cryopreservation of early mammalian embryos
      necessitates the study of the mechanisms of blastomere adaptation to the
      equilibration procedure and subsequent washing from the cryoprotector. The
      osmotic effects during these procedures can cause electrolyte imbalance in
      embryonic cells. Intracellular potassium concentrations at the stage of two
      blastomere mouse embryo were studied by electron probe microanalysis.

PMID- 15514719
TI  - Antigenic differences between apo-B in native and circulating modified low
      density lipoproteins.
AB  - The state of apo-B in native and circulating modified low-density lipoproteins
      was studied by solid-phase enzyme immunoassay. We studied the interaction of
      these particles with monoclonal antibodies to apo-B of low-density lipoproteins.
      Native and circulating modified low-density lipoproteins had different affinity
      for the studied antigens. Our results illustrate conformational changes in apo-B
      of circulating modified low-density lipoproteins compared to native low-density
      lipoproteins. These changes probably contribute to increased accumulation of
      particles in vascular cells and their transformation into foam cells giving way
      to atherosclerotic vascular lesions.

PMID- 15514720
TI  - Relationship between H+ transfer through human erythrocyte membrane and
      temperature.
AB  - The parameters of thermal dependence of H+ transport into human erythrocytes in
      the presence of furosemide were measured. The relationship between these changes
      and function of band 3 protein of the erythrocyte membrane is discussed.

PMID- 15514721
TI  - Effect of hypothermia on kinetic characteristics of acetylcholine esterase in rat
      erythrocyte membranes.
AB  - We studied kinetic and thermodynamic characteristics of acetylcholine esterase in
      rat erythrocyte membrane after whole-body hypothermia (20 degrees C) of different
      duration. Hypothermia increased the degree of substrate inhibition for
      acetylcholine esterase, maximum rate, and Michaelis constant. The temperature
      dependence of acetylcholine esterase activity remained practically unchanged.

PMID- 15514723
TI  - Effect of dehydroepiandrosterone on avoidance behavior of adult male rats.
AB  - We studied the effect of repeated intraperitoneal treatment with
      dehydroepiandrosterone in doses of 0.1 and 0.7 mg/kg on conditioned-response
      activity and behavior of adult male rats. The effect of dehydroepiandrosterone on
      learning was estimated in conditioned active and passive avoidance response
      paradigms. Chronic administration of dehydroepiandrosterone in low and high doses
      had no effect on retention of conditioned passive avoidance response in adult
      male rats 24 h after learning. However, chronic administration of
      dehydroepiandrosterone in low dose impaired acquisition of the conditioned active
      avoidance response. It should be emphasized that chronic administration of
      dehydroepiandrosterone in high dose did not modulate acquisition and retention of
      this reaction.

PMID- 15514722
TI  - Cold adaptation modulates Ca2+ signaling in brown preadipocytes.
AB  - One-week cold exposure of mice led to a 2-fold increase in the density of alpha1
      adrenoceptors in brown adipose tissue. The density of alpha1-adrenoceptors
      returned to normal after adaptation to cold for 2 weeks. The reduced Ca2+
      signaling in stem cells of brown fat activated via beta-adrenoceptors and cAMP
      was transformed into the Ca2+-system induced by alpha1-adrenoceptors and similar
      to that in mature brown adipocytes.

PMID- 15514724
TI  - Cerebroprotective effect of combined treatment with pyrazidol and bemitil in
      craniocerebral trauma.
AB  - Monotherapy of consequences of craniocerebral trauma with pyrazidol (1 mg/kg)
      produced an anxiolytic effect in animals highly resistant to hypoxia and
      activating effect on low resistant animals. Treatment with bemitil in a dose of
      25 mg/kg produced a cerebroprotective effect and normalized individual behavioral
      characteristics, parameters of energy metabolism, and state of the antioxidant
      system in the brain of highly and low resistant rats. The effect of bemitil was
      most pronounced in highly resistant animals. During combined treatment, pyrazidol
      and bemitil had an additive effect in animals of both groups. They normalized
      behavioral reactions and prevented the development of metabolic disturbances in
      the brain.

PMID- 15514725
TI  - Extract of Rhodiola rosea radix reduces the level of C-reactive protein and
      creatinine kinase in the blood.
AB  - The effects of extracts of Rhodiola rosea radix on blood levels of inflammatory C
      reactive protein and creatinine kinase were studied in healthy untrained
      volunteers before and after exhausting exercise. Rhodiola rosea extract exhibited
      an antiinflammatory effect and protected muscle tissue during exercise.

PMID- 15514727
TI  - Efficiency of refracterin in patients with chronic cardiac insufficiency caused
      by coronary heart disease.
AB  - Composite preparation refracterin administered in a dose of 300 mg/day for 3 days
      in addition to routine therapy significantly improved the results of treatment of
      severe cardiac insufficiency of ischemic genesis compared to placebo. Improvement
      of clinical status of patients is determined by positive dynamics of systolic and
      diastolic functions of the left ventricle.

PMID- 15514726
TI  - Taban-Arshan: immunocorrector in atopic bronchial asthma.
AB  - Taban-Arshan extract decreased expression of T-lymphocyte activation markers,
      normalized T-cell-mediated immunity, and suppressed increased activity of natural
      killer receptors during culturing with lymphocytes of patients with atopic
      bronchial asthma. Taban-Arshan extract normalized activation processes in the B
      cell immunity and stimulated expression of receptors of activation-induced
      apoptosis.

PMID- 15514728
TI  - Immunomodulating characteristics of Cys-(Pro)3-Glu-Leu hexapeptide under
      different experimental conditions.
AB  - Cys-(Pro)3-Glu-Leu hexapeptide markedly stimulated activity of human natural
      killers during the cytotoxic test in the presence of autologous serum, but not
      fetal calf serum. This effect of hexapeptide on natural killer activity was
      physiological. Conditions are determined under which hexapeptide stimulates the
      cytotoxicity in a mode ensuring protection of the microenvironment from damage
      inflicted by own natural killer cytotoxic factors.

PMID- 15514729
TI  - Alternative splicing of interleukin-6 mRNA in mice.
AB  - Expression of mRNA for interleukin-6, interleukin-6Delta3, and interleukin
      6Delta5 was detected in placental tissue (second and third trimesters of
      pregnancy) and spleen of mice immunized with sheep erythrocytes in high dose. We
      hypothesize that translation of mRNA yields proteins capable of binding to
      individual subunits of the interleukin-6 receptor and possessing effector
      functions.

PMID- 15514730
TI  - Tartrate-resistant acid phosphatase as a marker of bone metastases in patients
      with breast cancer and prostate cancer.
AB  - Serum activity of tartrate-resistant acid phosphatase 5b (TRAP 5b) in patients
      with breast cancer and prostate cancer having bone metastases was much higher
      than in healthy donors and patients without skeletal injuries. TRAP 5b activity
      in patients with breast cancer and multiple bone metastases surpassed that in
      patients with single bone metastases. The mean activity of TRAP 5b and range of
      enzyme activity in women treated with bisphosphonates were significantly lower
      than in patients not receiving antiresorptive therapy. Diagnostic sensitivity and
      specificity of TRAP 5b as a marker of skeletal metastases in patients with breast
      cancer were 82 and 87%, respectively. In patients with prostate cancer these
      indexes were 71 and 83.4%, respectively. Detection of this marker in tumor
      patients holds much promise for early diagnostics of bone metastases, estimation
      of the severity of skeletal metastases, and monitoring of the efficiency of
      bisphosphonate therapy.

PMID- 15514731
TI  - Peptide correction of age-related hormonal dysfunction of the pancreas in
      monkeys.
AB  - We studied the effect of Epithalon on the function of pancreatic islets and
      regulation of blood glucose level in female rhesus monkeys of various ages.
      Epithalon corrected the age-related decrease in glucose tolerance and restored
      the dynamics of insulin level in response to glucose load.

PMID- 15514732
TI  - Effect of antibodies to nerve growth factor and serum albumin on the development
      and behavior of mice.
AB  - We studied physical development, behavioral characteristics, and learning
      capacity in the offspring of mice immunized with nerve growth factor and bovine
      serum albumin. High titer of antibodies to these factors in the blood of pregnant
      females determines high levels of these antibodies in the blood of their pups.
      These changes modulate physical development, behavior, and learning capacity of
      rat pups. The effects of these antibodies differed in the strength and
      directionality. Antibodies to nerve growth factor more markedly retarded physical
      development, reduced learning capacity, and considerably increased pain
      thresholds in animals.

PMID- 15514733
TI  - Pathomorphology and pathogenic role of myocardial bridges in sudden cardiac
      death.
AB  - Pathognomonic incidence of myocardial bridges during obstructive hypertrophic
      cardiomyopathy, hypertension, and ischemic heart disease was established.
      Myocardial bridges were predominantly found in the median segments of major
      coronary arteries with prevailence of bridge-like obstructions in the anterior
      interventricular branch of the left coronary artery. Typical changes in cardiac
      angioarchitectonics indicating pronounced inadequacy of coronary blood flow were
      determined depending on the segmentary directionality of bridge obstruction. The
      data attest to pronounced pathogenetic role of myocardial bridges in sudden
      cardiac death.

PMID- 15514734
TI  - Histochemical study of mast cells from the thymus of mice receiving ACTH1-24.
AB  - Synthetic ACTH1-24 analogue administered in a daily dose of 0.01 mg/kg decreased
      the number and size of mast cells and increased intracellular serotonin
      concentration. ACTH1-24 induced degranulation of young mast cells and release of
      undersulfated heparin. Correlation analysis showed that hormonal imbalance
      produced by ACTH1-24 was accompanied by redistribution of bioamines.

PMID- 15514735
TI  - Arteriovenous anastomoses of major crural vessels in humans.
AB  - Arteriovenous anastomoses of the major crural vessels were studied postmortem.
      The revealed anastomoses were examined by histological technique.

PMID- 15514737
TI  - Method of experimental constriction of renal artery for modeling of renovascular
      hypertension in rats.
AB  - We propose a method of constriction of the renal artery consisting in pulling of
      a loop of isolated artery into a thin plastic tube with calibrated inner
      diameter. This method can be used in experiments with constriction of other small
      blood vessels to diminish the local blood flow.

PMID- 15514736
TI  - Use of morphostructural reaction of blood serum for toxicological evaluation of
      drugs.
AB  - We proposed a simple and economic method for determination of general toxic
      effects of drugs consisting in evaluation of serum morphology by polarization
      light microscopy.

PMID- 15514738
TI  - Structural characteristics of cardiomyocytes in the right atrium of NISAG rats.
AB  - Electron microscopy and stereomorphometric analysis of hypertrophic
      cardiomyocytes in the right atrium of NISAG rats revealed signs of activation of
      biosynthetic processes: increased relative volume of euchromatin (compared to
      Wistar rats), high density of nuclear pores, presence of large numerous Golgi
      complexes, and well-developed endoplasmic reticulum. The numerical density of
      secretory granules in the cytoplasm of cardiomyocytes in NISAG rats significantly
      surpassed that in Wistar rats. However, these granules in NISAG rats were smaller
      than in Wistar rats. The presence of numerous secretory granules and increased
      ratio of forming and dissolving structures suggest that this pool is
      characterized by high turnover rate, i.e., intensive synthesis and rapid
      elimination (consumption) of natriuretic peptide. Hypertrophy and hyperactivity
      of endocrine function in atrial cardiomyocytes of NISAG rats can be considered as
      a compensatory reaction to hypertension.

PMID- 15514739
TI  - Applications of the parahydrogen phenomenon in inorganic chemistry.
AB  - The study of reaction mechanisms by NMR spectroscopy normally suffers from
      limitations in sensitivity that arise from the physical constraints of the
      detection method. An overview is presented of how chemical reactions can be
      studied using parahydrogen assisted NMR spectroscopy where detected signal
      strengths can exceed those normally seen by factors of over 28,000.

PMID- 15514740
TI  - Diazenide and hydrazide(2-) derivatives of the [Re(CO)3]+ core.
AB  - Reaction of [ReBr3(CO)3]2- with aryldiazonium salts gives the Re(iii) diazenide
      complexes [ReBr2(NNC6H4R-4)(CO)2]-. The attachment of a PhNHCS tethering group to
      pyridyl hydrazine generates a HYNIC related proligand which gives a stable
      chelated pyridyliumthiocarbazide(2-) derivative of the [Re(I)(CO)3]+ core.

PMID- 15514741
TI  - Macropolyhedral boron-containing cluster chemistry. Cluster assembly about a
      molybdenum centre. Formation of the 19-vertex [(CO)2MoB16H15C2Ph2]- anion.
AB  - Fusion of nine-vertex [1-Ph-nido-1-CB8H11] with [Mo(CH3CN)3(CO)3] in the presence
      of tetramethylnaphthalenediamine gives the nineteen-vertex macropolyhedral
      metallaborane anion [(CO)2MoB16H15C2Ph2]- with a molybdenum(VI) twelve-atom
      coordination sphere.

PMID- 15514742
TI  - Solution-stable trinuclear zinc(II) cluster from 4-methyl-2-N-(2
      pyridylmethylene)aminophenol (HPyrimol).
AB  - The reaction of zinc(II) acetate with 4-methyl-2-N-(2-pyridylmethyl)aminophenol
      (HPyramol) in methanol leads to a solution stable linear trinuclear zinc cluster
      with intramolecular ligand oxidation.

PMID- 15514743
TI  - Further insights on the high-low spin interconversion in nickel(II) tetramine
      complexes. Solvent and temperature effects.
AB  - The spin interconversion equilibrium involving the [Ni(II)(cyclam)]2+ complex has
      been investigated in a variety of polar solvents, at varying temperatures. The
      greater the donor tendencies of the solvent, the higher the endothermicity of the
      high-to-low-spin conversion. In particular, a positive linear relationship exists
      between DeltaHdegrees and Gutmann's Donor Number (DN). In the same way, higher
      donor tendencies of the solvent favour the occurrence of the Ni(II)-to-Ni(III)
      oxidation process and negative linear relationship has been found between the
      E1/2(Ni(III)/Ni(II)) and DN. General behaviour is related to the intensity of the
      metal-solvent axial bonds in the octahedrally elongated cyclam complexes (of both
      Ni(II) and Ni(III)).

PMID- 15514744
TI  - Determination of the mode and efficacy of the cross-linking of guar by borate
      using MAS 11B NMR of borate cross-linked guar in combination with solution 11B
      NMR of model systems.
AB  - The reaction product of boric acid and the polysaccharide guaran (the major
      component of guar gum) has been investigated by 11B NMR spectroscopy. By
      comparison with the 11B NMR of boric acid and phenylboronic acid complexes of 1,2
      diols (HOCMe2CMe2OH, cis-C6H10(OH)2, trans-C6H10(OH)2, o-C6H4(OH)2), 1,3-diols
      (neol-H2), monosaccharides (L-fucose, mannose and galactose) and disaccharides
      (cellobiose and sucrose) it is found that the guaran polymer is cross-linked via
      a borate complex of two 1,2-diols both forming chelate 5-membered ring cycles
      ([B5(2)]), this contrasts with previous proposals. Based upon steric constraints
      we propose that preferential cross-linking the guaran polymer occurs via the 3,4
      diols of the galactose side chain. The DeltaH and DeltaS for complexation of
      boric acid to cis- and trans-1,2-cyclohexanediol have been determined, from the
      temperature dependence of the appropriate equilibrium constants, and used in
      conjunction with ab initio calculations on model compounds, to understand prior
      conflicting proposals for guaran-boric acid interactions. 11B NMR derived pH
      dependent equilibrium constants and ab initio calculations have been used to
      understand the reasons for the inefficiency of boric acid to cross-link guaran
      (almost 2 borate ions per 3 monosaccharide repeat units are required for a
      viscous gel suitable as a fracturing fluid): the most reactive sites on the
      component saccharides (mannose and galactose) are precluded from reaction by the
      nature of the guar structure; the comparable acidity (pKa) of the remaining
      guaran alcohol substituents and the water solvent, results in a competition
      between cross-linking and borate formation; a significant fraction of the boric
      acid is ineffective in cross-linking guar due to the modest equilibrium (Keq). In
      contrast to prior work, we present evidence for the reaction of alcohols with
      boric acid, rather than the borate anion. Based upon the results obtained for
      phenylboronic acid, alternative cross-linking agents are proposed.

PMID- 15514745
TI  - Preparation and structural characterisation of terpy-cored dendrimers and
      dendriplexes.
AB  - 2,2':6',2''-Terpyridine (terpy) ligands and their iron(II) and cobalt(II)
      complexes bearing first and second generation Frechet-type dendritic wedges have
      been prepared and structurally characterised. The rotational freedom within the
      dendritic wedge results in a great diversity in conformational space. Structural
      studies are reported on first generation species and their metal complexes, and
      the variety of inter- and intramolecular interactions which dominate the
      conformation of the dendrimer and the packing of the molecules (ions) in the
      lattice are discussed.

PMID- 15514746
TI  - A case for linear agostic interactions: identification by DFT calculation in a
      complex of Ta containing a uniquely caged triphenylmethyl C-H hydrogen.
AB  - Reaction of one equivalent of tris(3,5-di-tert-butyl-2-hydroxy)methane with TaCl5
      in CH2Cl2 along with Et3N gave a solid which on prolonged crystallisation led to
      a small quantity of crystalline material. An X-ray crystal structure
      determination showed one crystal was [TaCl3[[OC6H2(CMe3)2-2,4]3CH]]-
      Et2NH2+.3C6H6.1.5H2O with the anion consisting of three chloro ligands and three
      phenoxides of the tripodal ligand about the tantalum centre. The triphenylmethyl
      group proton was located and refined and was found to be enclosed in a cage
      making contacts of 2.09(8), 2.09(8) and 1.89(12)A with the phenoxide ligand
      oxygens consistent with weak C-H bond hydrogen bonding. The hydrogen atom points
      at the tantalum atom at a distance of 2.14(11) A from it, the TaH-C angle is 166
      degrees and the C-H bond distance is 1.04(12) A. DFT calculations at the B3LYP
      level indicate that where a hydrogen atom is attached to the triphenylmethyl
      carbon on the inside of the cage, there is good agreement with the crystal
      structure. The C-H bond points directly at the tantalum centre and an NBO
      analysis indicates there is significant overlap of the triphenylmethyl C-H bond
      electron density in a linear sense with an "unfilled" metal d orbital. Based on
      the NBO analysis, the C-HTa overlap would appear to be an example of a linear
      agostic interaction under the definition of agostic bonding.

PMID- 15514747
TI  - Carbonyl analogues? Analysis of Fe-E (E=B, Al, Ga) bonding in cationic terminal
      diyl complexes by density functional theory.
AB  - A series of DFT calculations has been carried out with the aim of characterizing
      the metal-group 13 element interaction in the novel cationic borylene complex
      [(eta5-C2Me5)Fe(CO)2(BMes)]+ (1) and related species of the type [eta5
      C5R5)M(L)2(EX)]n+. In addition, comparisons have been made with charge neutral
      borylene complexes and with related group 14 based ligand systems (e.g. cationic
      metal carbonyls, carbenes and vinylidenes) for which models of bonding have
      previously been established. In this regard particular attention has been focused
      on the interpretation of (i) molecular orbital composition; (ii) bond
      dissociation energies (BDEs) and the ratio of ionic to covalent contributions
      (DeltaEelstat/DeltaEorb); and (iii) sigma and pi symmetry covalent contributions.
      The molecular orbital compositions for the prototype borylene complex 1 and for
      related cationic and neutral systems [e.g.[(eta5-C5H5)Fe(PMe3)2(BMes)]+ and (eta5
      C5H5)Mn(CO2(BMes)]] are consistent with the presence of bonding interactions
      between metal and borylene fragments of both sigma and pi symmetry. Furthermore,
      on the basis of BDEs, DeltaEorb values and sigma/pi covalent ratios, the bonding
      in cationic terminal borylene complexes such as 1 appears to have as much right
      to be termed a M=E double bond as does that in archetypal Fischer carbene and
      related complexes such as [(eta5-C5R5)Fe(CO)2(CCMe2)]+ and [(eta5
      C5R5)Fe(CO)2(CH2)]+.

PMID- 15514748
TI  - Isolation and characterization of iridium(III) and iridium(V) complexes of 2
      (arylazo)pyridine and studies of amine fusion reactions at the coordinated diazo
      ligand.
AB  - The reaction of IrCl3.3H2O with 2-(arylazo)pyridine (HL1) in boiling methanol has
      afforded [Ir(III)Cl2(L1)(HL1)](1) and [Ir(V)Cl4(HL1)]Cl (2). In complex , one of
      the two ligands [L1]- is orthometallated via coordination of an ortho-carbon of
      the aryl ring of [L1]- and one of the two azo nitrogens to form a five-membered
      chelate. X-Ray crystal structures of the two representative complexes, viz. 1a
      and 2a, have been solved. Notably, the Ir-N length (2.140(3) A)trans to the Ir-C
      bond in 1a is appreciably longer than the other three Ir-N lengths present in the
      same molecule. The N-N lengths in these two compounds lie close to that observed
      in the uncoordinated ligand. Thorough NMR studies were made to authenticate the
      carbon-bonded structure of compound 1a. In its 13C NMR spectrum, the resonance
      near delta 148 is assigned to the carbon bonded to the iridium metal center. UV
      visible spectra along with the redox properties of these complexes are reported.
      The iridium(V) complex, 2 showed a reversible response near 1.40 V, presumably
      due to the iridium(V)-iridium(VI) couple. Several reductive responses at cathodic
      potentials, due to ligand reductions, were also observed. Metal promoted aromatic
      ring amination reactions at the coordinated HL1 ligand in complexes 1 and 2 were
      investigated. The products were characterized using X-ray diffraction.

PMID- 15514750
TI  - Synthesis and magnetism of oxygen-bridged tetranuclear defect dicubane Co(II) and
      Ni(II) clusters.
AB  - Reaction of aqueous/ethanolic solutions of CoCl2.6H2O and nitrilotripropionic
      acid (H3ntp=N(CH2CH2COOH)3) in the presence of potassium hydroxide affords the
      hydroxy-bridged tetranuclear cluster [Co4mu3-OH)2(H2O)6(ntp)2].2H2O (1). The
      Ni(II) analogue [Ni4(mu3-OH)2(H2O)6(ntp)2].2H2O (2) can also be isolated using
      aqueous solutions and Ni(SO4).7H2O as metal salt. With small changes in reaction
      conditions the methoxy-bridged analogue, [Ni4(mu3-OMe)2(H2O)6(ntp)2](3), can also
      be isolated. In these tetramers the M(II) ions are oxygen-bridged and exhibit a
      defect dicubane-like core with two missing vertices. The magnetic properties have
      been studied for all three clusters and reveal competing antiferromagnetic and
      ferromagnetic interactions between the four Co(II) ions in 1 and ferromagnetic
      coupling between the four Ni(II) ions in 2 and 3. In all three compounds the
      individual clusters order antiferromagnetically at Neel temperatures below 1 K.

PMID- 15514749
TI  - Intramolecularly hydrogen-bonded versus copper(II) coordinated mono- and bis
      phenoxyl radicals.
AB  - Ligands bearing two salicylidene imine moieties substituted in ortho and para
      positions by tert-butyl groups have been electrochemically oxidized into mono-
      and bis-phenoxyl radicals. The process involves an intramolecular proton coupled
      to electron transfer and affords a radical in which the oxygen atom is hydrogen
      bonded to a protonated ammonium or iminium group. A weak intramolecular dipolar
      interaction exists between the two phenoxyl moieties in the bis-radical species.
      The copper(II) complexes of these ligands have been characterized and
      electrochemically oxidized. The mono-phenoxyl radical species are X-band EPR
      silent. The bis-phenoxyl radical species exhibits a (S= 3/2) ground state: it
      arises from a ferromagnetic exchange coupling between the two spins of the
      radicals and that of the copper(II) when the spacer is rigid enough; a flexible
      spacer such as ethylidene induces decomplexation of at least one phenoxyl group.
      Metal coordination is more efficient than hydrogen-bonding to enhance the
      chemical stability of the mono-phenoxyl radicals.

PMID- 15514751
TI  - Synthesis and characterization of tin containing polyhedral
      oligometallasilsesquioxanes (POMSS).
AB  - Tin silicate species have shown good catalytic activity in various oxidation
      reactions. In an attempt to mimic surface tin species, several tin containing
      silsesquioxanes have been synthesized. Incompletely condensed silsesquioxanes (c
      C5H9)7Si7O9(OH)3 and (c-C5H9)7Si7O9(OSiMe3)(OH)2 were reacted with common tin
      precursors, which afforded several silsesquioxane ligated tin compounds. Divalent
      stannasilsesquioxanes form dimers of the type [(c-C5H9)7Si7O11(OX)Sn]2(X=H,
      SiMe3) with three-coordinated tin centers. The three-coordinated tin(II) are
      hydrolytically unstable whereas the octahedrally surrounded tetravalent
      stannasilsesquioxanes [(c-C5H9)7Si7O11(OX)]Sn(acac)2(X=H, OSiMe3) are
      hydrolytically robust. An unprecedented anionic trimeric cluster, [[(c
      C5H9)7Si7O12Sn]3(mu2-OH)3(mu3-OH)]-[HNEt3]+, stabilized by bridging hydroxyl
      groups was formed when the product formed upon reacting (c-C5H9)7Si7O9(OH)3 with
      SnCl4 was slowly hydrolyzed. The stannasilsesquioxanes showed no catalytic
      activity in oxidation reactions.

PMID- 15514753
TI  - Palladacyclic complexes bearing CNN-type ligands as catalysts in the Heck
      reaction.
AB  - Preparations of novel unsymmetrical, tridentate nitrogen ligand precursors,
      PhN=C(CMe2)(NPh)C=N(CH2)2NMe2(1) and PhN=C(CMe2)(NPh)C=N(CH2)Py (2), are
      described. Treatment of 1 with 1 molar equiv. (COD)PdCl2 in the presence of NEt3
      or with 1 molar equiv. Pd(OAc)2 affords orthometallated palladium(II) complexes,
      [PhN=C(CMe2)(N-eta1-Ph)C=N(CH2)2NMe2]PdX (X=Cl (3); X=OAc (4)), respectively.
      Compound can be yielded via the reaction of with an excess of LiCl in methanol.
      Treatment of with 1 molar equiv. of (COD)PdCl2, Pd(OAc)2 or Pd(TFA)2 affords
      orthometallated palladium(II) complexes, [PhN=C(CMe2)(N-eta1-Ph)C=NCH2Py]PdX
      (X=Cl (5); X=OAc (6); X=TFA (7)), respectively. The crystal and molecular
      structures are reported for compounds 2, 3, 5 and 6. The application of these
      novel palladacyclic complexes to the Heck reaction with aryl halide substrates
      was examined.

PMID- 15514752
TI  - A mass spectrometric investigation of non-covalent interactions between ruthenium
      complexes and DNA.
AB  - Electrospray ionisation mass spectrometry was used to investigate reactions
      between six ruthenium compounds and three different non self-complementary duplex
      oligonucleotides containing 16 base pairs. Each of the compounds studied formed
      non-covalent complexes containing between one and five ruthenium molecules bound
      to DNA. Competition experiments involving duplex 16mers and pairs of ruthenium
      compounds were used to determine the order of relative binding affinities of the
      metal compounds. Other competition experiments involving ruthenium compounds, and
      the organic DNA binding agents daunomycin and distamycin, provided information
      about the sites and modes of DNA binding of the ruthenium compounds.

PMID- 15514754
TI  - Synthesis, structure and heterogeneous catalytic activities of Cu-containing
      polymeric compounds: anion effect and comparison of homogeneous vs. heterogeneous
      catalytic activity.
AB  - The structures of new polymeric compounds containing Cu(II) ions and btp (2,6
      bis(N'-1,2,4-triazolyl)pyridine) ligands have been determined. The btp ligands
      bridge Cu(II) ions to form double zigzag chains, [Cu(ClO4)2(btp)2] 3 with
      perchlorate anions, and form single zigzag chains, [Cu(btp)(H2O)4](SO4).2H2O 4
      with sulfate anions. The polymeric compound 3 was found to effectively catalyze
      the epoxide ring-opening reaction with methanol, while polymeric compound 4 was
      almost inactive with epoxides under the same conditions. The polymeric compound 3
      showed an efficient catalytic activity and regioselective reactivity in the ring
      opening of epoxides and allowed reuse without a significant loss of activity
      through three runs with epoxides.

PMID- 15514755
TI  - Copper(II) complexes of N-terminal protected tri- and tetra-peptides containing
      histidine residues.
AB  - Copper(II) complexes of peptides containing two or three histidyl residues (Ac
      HisGlyHis-OH, Ac-HisGlyHis-NHMe, Ac-HisHisGlyHis-OH and Ac-HisHisGlyHis-NHMe)
      have been studied by potentiometric, UV-Vis, EPR and CD spectroscopic
      measurements. The imidazole nitrogen atoms are described as the primary metal
      binding sites of all ligands resulting in the formation of various macrochelates
      in the pH range 4 to 7. The (Nim, N-, Nim)-co-ordinated [CuH-1L]0+ complexes were
      mainly detected in samples containing free carboxylates at the C-termini, whilst
      the [CuH-2L]-(0) complexes were the predominant species in slightly alkaline
      solution and their binding modes were described via 4N-co-ordination (Nim, N-, N
      , Nim) in (7,5,6)-membered fused chelate rings. Deprotonation and co-ordination
      of the third amide nitrogens were detected above pH approximately 9 in all cases.

PMID- 15514756
TI  - Reaction of BH4- with [Mo2Cp2(mu-SMe)n] species to give tetrahydroborato, hydrido
      or dimetallaborane compounds: control of product by ancillary ligands.
AB  - The reaction of mono- or dichloro-dimolybdenum(III) complexes [Mo2Cp2(mu-SMe)2(mu
      Cl)(mu-Y)] (Cp=eta5-C5H5; 1, Y=SMe; 2, Y=PPh2; 3, Y=Cl) with NaBH4 at room
      temperature gave in high yields tetrahydroborato (8), hydrido (9) or
      metallaborane (12) complexes depending on the ancillary ligands. The correct
      formulation of derivatives and has been unambigously determined by X-ray
      diffraction methods. That of the hydrido compound 9 has been established in
      solution by NMR analysis and confirmed by an X-ray study of the mu-azavinylidene
      derivative [Mo2Cp2(mu-SMe)2(mu-PPh2)(mu-N=CHMe)] (10) obtained from the insertion
      of acetonitrile into the Mo-H bond of 9. Reaction of NaBH4 with nitrile
      derivatives, [Mo2Cp2(mu-SMe)4-n(CH3CN)2n]n+(5, n=1; 6 n=2), afforded the
      tetrahydroborato compound 8, together with a mu-azavinylidene species [Mo2Cp2(mu
      SMe)3(mu-N=CHMe)](14), when n=1, and the metallaborane complex 12, together with
      a mixed borohydrato-azavinylidene derivative [Mo2Cp2(mu-SMe)2(mu-BH4)(mu-N=CHMe)]
      (13), when n=2. The molecular structures of these complexes have been confirmed
      by X-ray analysis. Preparations of some of the starting complexes (3 and 4) are
      also described, as are the molecular structures of the precursors [Mo2Cp2(mu
      SMe)2(mu-X)(mu-Y)] (1, X/Y=Cl/SMe; 2, X/Y=Cl/PPh2; 4, X/Y=SMe/PPh2).

PMID- 15514757
TI  - Synthesis, molecular structures, and chemistry of some new palladium(II) and
      platinum(II) complexes with pentafluorophenyl ligands.
AB  - A series of palladium(II) and platinum(II) complexes possessing pentafluorophenyl
      ligands of the general formula [M(L-L)(C6F5)Cl][space](M = Pd 3; L-L=tmeda
      (N,N,N',N',-tetramethylethylenediamine) a; 1,2-bis(2,6
      dimethylphenylimino)ethane) b; dmpe (1,2-bis(dimethylphosphino)ethane) c; dcpe
      (1,2-bis(dicyclohexylphosphino)ethane) d; Pt ; L-L=tmeda a; 1,2-bis[3,5
      bis(trifluoromethyl)phenylimino]-1,2-dimethylethane b; dmpe c; dcpe d) were
      readily synthesized from the dimer [M(C6F5)(tht)(mu-Cl)2] (M=Pd 1b, Pt 2b;
      tht=tetrahydrothiophene) and the corresponding bidentate ligand. In the case of
      palladium, the corresponding iodo analogues (6a-c) were readily synthesized in a
      one-pot reaction from [Pd2(dba)3], iodopentafluorobenzene, and the appropriate
      ligand. The platinum complexes 4c-d were then converted to the water complexes
      [Pt(L-L)(C6F5)(OH2)]OTf (L-L =dmpe 7a; dcpe 7b)via reaction with AgOTf in the
      presence of water. Attempts to convert the palladium complexes 3c-d to the
      corresponding water complexes resulted in the disproportionation of the
      intermediate water complex to form [Pd(L-L)(C6F5)2] (L-L=dmpe 8) or [Pd(L
      L)2][OTf]2(L-L=dcpe 9). Upon standing in solution for prolonged periods, complex
      7a undergoes an identical disproportionation reaction to the Pd analogues to form
      [Pt(L-L)(C6F5)2] (L-L=dmpe 10). Complexes 4c and 4d were converted to the
      corresponding hydrides (11b-c, respectively) using two different hydride sources:
      11a was formed by the reaction of with NaBH4 in refluxing THF, while 11b was
      synthesized in near quantitative yield using [Cp2ZrH2] in refluxing THF. Attempts
      to synthesize eta2-tetrafluorobenzyne complexes [Pt(L-L)(C6F4)] (L-L=dmpe, dcpe)
      from reaction of 11a-b with butyllithium were unsuccessful. The molecular
      structures of 3a,4a, 4c, 4d, 6b, 7a, 8, 11b and have been determined by X-ray
      crystallographic studies, and are discussed.

PMID- 15514758
TI  - The metalla-Pinner reaction between Pt(IV)-bound nitriles and alkylated oxamic
      and oximic forms of hydroxamic acids.
AB  - The nitrile ligands in the platinum(IV) complexes trans-[PtCl4(RCN)2] (R=Me, Et,
      CH2Ph) and cis/trans-[PtCl4(MeCN)(Me2SO)] are involved in a metalla-Pinner
      reaction with N-methylbenzohydroxamic acid (N-alkylated form of hydroxamic acid,
      hydroxamic form; F1), PhC(=O)N(Me)OH, to achieve the imino species
      [PtCl4[NH=C(R)ON(Me)C(=O)Ph]2 (1-3) and [PtCl4[NH=C(Me)ON(Me)C(=O)Ph](Me2SO)]
      (7), respectively. Treatment of trans-[PtCl4(RCN)2] (R=Me, Et) and cis/trans
      [PtCl4(MeCN)(Me2SO)] with the O-alkylated form of a hydroxamic acid (hydroximic
      form), i.e. methyl 2,4,6-trimethylbenzohydroximate, 2,4,6-(Me3C6H2)C(OMe)=NOH
      (F2A), allows the isolation of [PtCl4[NH=C(R)ON=C(OMe)(2,4,6-Me3C6H2)]2] (5, 6)
      and [PtCl4[NH=C(Me)ON=C(OMe)(2,4,6-Me3C6H2)](Me2SO)] (8), correspondingly. In
      accord with the latter reaction, the coupling of nitriles in trans-[PtCl4(EtCN)2]
      with methyl benzohydroximate, PhC(OMe)=NOH (F2B), gives
      [PtCl4[NH=C(Et)ON=C(OMe)Ph]2] (4). The addition proceeds faster with the
      hydroximic F2, rather than with the hydroxamic form F1. The complexes 1-8 were
      characterized by C, H, N elemental analyses, FAB+ mass-spectrometry, IR, 1H and
      13C[1H] NMR spectroscopies. The X-ray structure determinations have been
      performed for both hydroxamic and hydroximic complexes, i.e. 2 and 6, indicating
      that the imino ligands are mutually trans and they are in the E-configuration.

PMID- 15514759
TI  - Hydrogen-bond mediation of supramolecular aggregation in neutral bis-(C6F5)Pt
      complexes with aromatic H-bond donating ligands. A synthetic and structural
      study.
AB  - Six pentafluorophenylplatinum(II) complexes containing proton acceptor atoms (F)
      and pyridine-like aromatic ligands able to act as proton donors have been
      synthesized and characterized, with emphasis on the factors that mediate their
      supramolecular aggregation in the solid state--hydrogen bonds and pi-pi
      interactions. The crystal structure analyses of the mononuclear complexes cis
      [Pt(C6F5)2(napy)](1), cis-[Pt(C6F5)2(CH2napy)](3), cis-[Pt(C6F5)2(2-ammpy)](5),
      and cis-[Pt(C6F5)2(2-bipym)](6) reveal the influence of D-HPt and D-HF (D=C, N)
      hydrogen bonding on the organization of molecules into stacks, which can be
      further interconnected to generate channels. The prevalence of hydrogen bonding
      over pi-pi interactions between aromatic rings in establishing the nature of the
      observed supramolecular aggregation is demonstrated.

PMID- 15514760
TI  - Unprecedented single-pot synthesis of nitrile-derived ketoimino platinum(II)
      complexes by ring opening of Delta4-1,2,4-oxadiazolines.
AB  - [PtCl2(RCN)2] (1a R=CH2CO2Me, 1b R=CH2Cl) prepared upon EtCN replacement at
      [PtCl2(EtCN)2] by the appropriate organonitrile, react with a cyclic nitrone -O
      +N=CHCH2CH2C(Me)2, under mild conditions, to give, in an unprecedented single-pot
      synthesis involving spontaneous N-O bond cleavage, the ketoimino complexes trans
      [PtCl2[RC(=O)N=CN(H)C(Me)2-CH2CH2]2 (2a, 2b) with two (pyrrolidin-2-ylidene)amino
      ligands. The analogous 2c (R=Et) and 2d (R=Ph) are formed by treatment with H2,
      in the absence of any added catalyst, of the Delta4-1,2,4-oxadiazoline complexes
      trans-[PtCl2[N=C(R)ONC(Me)2CH2CH2CH]2] (3a R=Et, 3b R=Ph) derived from the [2 +
      3]-cycloaddition of the cyclic nitrone with the appropriate organonitrile complex
      of type 1. The compounds were characterized by elemental analyses, IR, 1H, (13C
      and 195Pt NMR spectroscopies, FAB mass spectrometry and X-ray structure analyses
      for 2a and 2d.

PMID- 15514761
TI  - Direct reaction of photogenerated diarylcarbenes at square-planar rhodium(I).
AB  - A series of carbene complexes RhCl(CR'2)(PR3)2(R=Ph, Tol, Me, R'= Ph and Tol)
      have been synthesised through direct reaction of photochemically generated free
      diarylcarbene with RhCl(CO)(PR3)2. This route to carbene complexes demonstrates
      the reactivity of simple diarylcarbenes towards transition metal complexes. The
      reactivity of some of these complexes towards H2, C2H4 and Et3SiH has been
      investigated.

PMID- 15514762
TI  - On, off and intermediate coordination of a bridgehead triarylamine donor in
      tripodal complexes: towards the tuning of coordinative bond distance.
AB  - A series of first row transition metal complexes of the tripodal ligand 2,2',2"
      nitrilotribenzoic acid H3L has been prepared and characterised by X-ray
      crystallography: Mononuclear [M(L)]- species [Cu(H2O)4]3[Cu(L)(H2O)]6.25H2O (2),
      [Co(H2O)6][Co(L)(H2O)].8H2O (4), [Zn(H2O)6][Zn(L)(H2O)].8H2O (5) and a neutral
      [M(L)] complex [Fe(III)2(L)(H2O)3].5H2O (8) are formed as well as dimeric [M(L)]2
      2- species (HNEt3)2[Cu(L)]2.2CH3CN (1), (HNEt3)3[Ni(L)]2(ClO4).H2O (3),
      (HNEt3)2[Fe(II)(L)]2.2CH3CN (6) and (HNEt3)2[Fe(III)2(L)2(mu-O)](7). The
      complexes display a unique variation in the M-N distance (2.09 A for Cu(II) to
      3.29 A for Fe(III)) to the bridgehead triphenylamine donor and are classified
      into compounds with "On","Off" and "Intermediate" N-coordination. The trigonal
      bipyramidal coordination polyhedron changes towards tetrahedral in the
      intermediate and octahedral in the Off-state. The M-N distance of individual
      complexes is reversibly tuned by external chemical input such as changes of metal
      ion oxidation state (Fe(II)/Fe(III)) or variation of the axial coligand as a
      consequence of solvent or pH variation. Possible reasons for the exceptional
      tolerance of the M-N bond to distance variations are discussed under
      consideration of gas phase DFT calculations of [Zn(L)]-.

PMID- 15514763
TI  - Nickel pivalate complexes: structural variations and magnetic susceptibility and
      inelastic neutron scattering studies.
AB  - The synthesis and structural characterisation of three small nickel(II) cages are
      reported, all stabilised by pivalate ligands. The magnetic properties of the
      cages have been studied by a combination of susceptibility measurements and
      inelastic neutron scattering. For a dinuclear cage, [Ni2(mu
      OH2)(O2CCMe3)4(HO2CCMe3)4] 1 the ground state is S=2, with a ferromagnetic
      exchange interaction between the Ni(II) centres of J=0.32 meV and D(S=2)=-0.09
      meV in the ground state. For a tetranuclear heterocubane cage, [Ni4(mu(3)
      OMe)4(O2CCMe3)4(MeOH)4] 2, two ferromagnetic exchange interactions are found and
      an S=4 ground state observed. While the zero-field splitting of this state cannot
      be determined unambigiously the most likely value is DS=4=-0.035 meV. For a
      tetranuclear nickel butterfly, [Ni4(mu3-OH)2(O2CCMe3)6(EtOH)6] 3, three exchange
      interactions are required, two anti-ferromagnetic and one weakly ferromagnetic;
      the resulting ground state is S=0. The data enable us to estimate the zero-field
      splitting of single Ni(II) ions involved in the cage as Di=+1.0 meV. Both and are
      therefore expected to be new single molecule magnets.

PMID- 15514764
TI  - Synthesis of new poly(propylenimine) dendrimers DAB-dendr
      [NH(O)COCH2CH2OC(O)C5H4Rh(NBD)](n) [n=4, 8, 16, 32, 64] functionalized with
      alkoxycarbonylcyclopentadienyl complexes of rhodium(I).
AB  - The reaction between [Rh[C5H4CO2(CH)2OH](NBD)] (1) and 1,1'-carbonyldiimidazole
      (CDI) leads to the new CO2-imidazole functionalized
      alkoxycarbonylcyclopentadienyl complex [Rh[C5H4CO2(CH2)2O2C-Im](NBD)] (2)
      (Im=imidazole). The latter was treated with five generations of
      poly(propylenimine) dendrimers DAB-dendr-(NH2)(n) [n=4, 8, 16, 32, 64]
      (DAB=diaminobutane) to accomplish the synthesis of the new organometallic
      dendritic macromolecules DAB-dendr-[NH(O)COCH2CH2OC(O)C5H4Rh(NBD)](n) [n=4 (4), 8
      (5), 16 (6), 32 (7), 64 (8)] based on flexible poly(propylenimine) dendrimer
      cores, built up to the fifth generation. Spectroscopic characterization of all
      the new compounds will be presented and discussed.

PMID- 15514765
TI  - A new pyridine-based 12-membered macrocycle functionalised with different
      fluorescent subunits; coordination chemistry towards Cu(II), Zn(II), Cd(II),
      Hg(II), and Pb(II).
AB  - The coordination chemistry of the new pyridine-based, N2S2-donating 12-membered
      macrocycle 2,8-dithia-5-aza-2,6-pyridinophane (L1) towards Cu(II), Zn(II),
      Cd(II), Hg(II), and Pb(II) has been investigated both in aqueous solution and in
      the solid state. The protonation constants for L1 and stability constants with
      the aforementioned metal ions have been determined potentiometrically and
      compared with those of ligand L2, which contains a N-aminopropyl side arm. The
      measured values show that Hg(II) in water has the highest affinity for both
      ligands followed by Cu(II), Cd(II), Pb(II), and Zn(II). For each metal ion
      considered, 1:1 complexes with L1 have also been isolated in the solid state,
      those of Cu(II) and Zn(II) having also been characterised by X-ray
      crystallography. In both complexes L1 adopts a folded conformation and the
      coordination environments around the two metal centres are very similar: four
      positions of a distorted octahedral coordination sphere are occupied by the donor
      atoms of the macrocyclic ligand, and the two mutually cis-positions unoccupied by
      L1 accommodate monodentate NO3- ligands. The macrocycle L1 has then been
      functionalised with different fluorogenic subunits. In particular, the N
      dansylamidopropyl (L3), N-(9-anthracenyl)methyl (L4), and N-(8-hydroxy-2
      quinolinyl)methyl (L5) pendant arm derivatives of L1 have been synthesised and
      their optical response to the above mentioned metal ions investigated in MeCN/H2O
      (4:1 v/v) solutions.

PMID- 15514766
TI  - Formation of heterotopic metallacalix[n]arenes (n=3, 4, 6) containing
      ethylenediaminepalladium(II) metal fragments and 4,7-phenanthroline and 2
      pyrimidinolate bridges. Synthesis, structure and host-guest chemistry.
AB  - A multicomponent reaction involving ethylenediaminepalladium(II), 2-pyrimidinol
      derivatives (L) [L=2-pyrimidinol (a); 4-methyl-2-pyrimidinol (b); 4,6-dimethyl-2
      pyrimidinol (c)] and 4,7-phenanthroline (4,7-phen) leads to the formation of
      heterotopic cyclic metallamacrocycles of the type [Pdn(en)n(mu-N,N'-L)m(mu-N,N'
      4,7-phen)n-m](2n-m)+ [n=3, m=1 (3); n=4, m=2 (4); n=6, m=4 (5)]. These species
      can be obtained by different reaction pathways, including: (i) reaction of
      ethylenediaminepalladium(ii), L and 4,7-phen building blocks and (ii) reaction of
      the homotopic species [Pd4(en)4(mu-N,N'-L)4]4+ (1) and [Pd3(en)3(mu-N,N'-4,7
      phen)3]6+ (2). The resulting heterotopic metallamacrocycles have been
      characterised by 1D and 2D 1H NMR spectroscopy. Additionally, species 3c and 4a
      have been studied by X-ray crystallography. The former one contains almost
      isosceles triangles of [Pd3(en)3(mu-N,N'-4,6-dimethyl-2-pyrimidinolate)(mu
      N,N[prime or minute]-4,7-phen)2]5+ formulation, exhibiting a pinched-cone
      conformation. 4a contains a tetranuclear parallelogram [Pd4(en)4(mu-N,N'-2
      pyrimidinolate)2(mu-N,N'-4,7-phenanthroline)2]6+, exhibiting a 1,3-alternate
      conformation. The host-guest properties of the here reported species have been
      studied, showing that they are able to interact with cationic as well as with
      anionic species.

PMID- 15514767
TI  - Exo-pi-bonding to an ortho-carborane hypercarbon atom: systematic icosahedral
      cage distortions reflected in the structures of the fluoro-, hydroxy- and amino
      carboranes, 1-X-2-Ph-1,2-C2B10H10 (X=F, OH or NH2) and related anions.
AB  - The structures of derivatives of phenyl-ortho-carborane bearing on the second
      cage hypercarbon atom a pi-donor substituent (F, OH, O-, NH2, NH- and CH2-) were
      investigated by NMR, X-ray crystallography and computational studies. The
      molecular structures of these compounds, notably their cage C1-C2 distances and
      the orientations of their pi-donor substituents (OH, NH2, NH- and CH2-) show
      remarkable and systematic variations with the degree of exo pi-bonding, which
      varies as expected with the pi-donor characteristics of the substituent.

PMID- 15514768
TI  - LZnX complexes of tripodal ligands with intramolecular RN-H hydrogen bonding
      groups: structural implications of a hydrogen bonding cavity, and of X/R in the
      hydrogen bonding geometry/strength.
AB  - Tripodal ligands N(CH2Py)3-n(CH2Py-6-NHR)n(R=H, n=1-3 L1-3, n=0 tpa; R=CH2tBu,
      n=1-3 L'1-3) are used to investigate the effect of different hydrogen bonding
      microenvironments on structural features of their LZnX complexes (X=Cl-, NO3-, OH
      ). The X-ray structures of [(L2)Zn(Cl)](BPh4)2.0.5(H2O.CH3CN),
      [(L3)Zn(Cl)](BPh4)3.CH3CN, [(L'1)Zn(Cl)](BPh4) 1', [(L'2)Zn(Cl)](BPh4)2'.CH3OH,
      and [(L'3)Zn(Cl)](BPh4)3' have been determined and exhibit trigonal bipyramidal
      geometries with intramolecular (internal) N-HCl-Zn hydrogen bonds. The structure
      of [(L'2)Zn(ONO2)]NO3 4'.H2O with two internal N-HO-Zn hydrogen bonds has also
      been determined. The axial Zn-Cl distance lengthens from 2.275 A in
      [(tpa)Zn(Cl)](BPh4) to 2.280-2.347 A in 1-3, 1'-3'. Notably, the average Zn-N(py)
      distance is also progressively lengthened from 2.069 A in [(tpa)Zn(Cl)](BPh4) to
      2.159 and 2.182 A in the triply hydrogen bonding cavity of 3 and 3',
      respectively. Lengthening of the Zn-Cl and Zn-N(py) bonds is accompanied by a
      progressive shortening of the trans Zn-N bond from 2.271 A in [(tpa)Zn(Cl)](BPh4)
      to 2.115 A in 3 (2.113 A in 3'). As a result of the triply hydrogen bonding
      microenvironment the Zn-Cl and Zn-N(py) distances of 3 are at the upper end of
      the range observed for axial Zn-Cl bonds, whereas the axial Zn-N distance is one
      of shortest among N4 ligands that induce a trigonal bipyramidal geometry. Despite
      the rigidity of these tripodal ligands, the geometry of the intramolecular RN-HX
      Zn hydrogen bonds (X=Cl-, OH-, NO3-) is strongly dependent on the nature of X,
      however, on average, similar for R=H, CH2tBu.

PMID- 15514769
TI  - Synthesis and characterization of [(diene)Rh[mu-OSi(OtBu)3]]2, a precursor to
      silica-bound rhodium.
AB  - Reaction of [(diene)RhCl]2 with 2 equiv of KOSi(OtBu)3 afforded [(diene)Rh[mu
      OSi(OtBu)3]]2, where diene=cod (1) and nbd (2). Multinuclear NMR studies reveal
      that 1 and 2 have a dimeric structure with bridging tris(tert-butoxy)siloxy
      ligands. These dimers are folded along the O...O axis. Complexes and reacted with
      PR3(R=Me, Ph) to give monomeric products, the formulae of which depend on the
      amount of PR3 added ((diene)Rh[OSi(OtBu)3](PR3) and Rh[OSi(OtBu)3](PMe3)3). The
      behavior of 1 towards water and methanol is discussed. Thermogravimetric analyses
      (TGAs) of 1 and 2 reveal rather sharp conversions to rhodium-containing
      materials. Thermolysis of 1 in toluene at 180 degrees C resulted in formation of
      a black precipitate, which contained rhodium nanoparticles with an average
      diameter of 22 nm, as determined by powder X-ray diffraction (PXRD), after
      calcination at 300 degrees C for 1 h.

PMID- 15514770
TI  - Oxygen and nitrogen Lewis base adducts of [UO2(OTf)2]. Crystal structures of
      polypyridine complexes with out-of-plane uranyl equatorial coordination.
AB  - Dissolution of [UO2(OTf)2](1) in anhydrous thf, dme or py led to the formation of
      the complexes [UO2(OTf)2(thf)3](2), [UO2(OTf)2(dme)](3) and [UO2(OTf)2(py)3](4),
      respectively. Compounds 2 and 4 are neutral monomers in the solid state as well
      as the chloride [UO2Cl2(py)3](5) which was prepared in a similar way as for from
      the dimer [[UO2Cl2(thf)2]2]. Addition of 4 equivalents of triphenylphosphine
      oxide (tppo) to 1 afforded, in pyridine, the dicationic species
      [UO2(tppo)4][OTf]2 (6). The bi- or terdentate nitrogen molecules 2,2'-bipy, phen
      or terpy reacted with 1 in acetonitrile or pyridine to give
      [UO2(OTf)2(bipy)2](7), [UO2(phen)3][OTf]2(8), [UO2(OTf)2(terpy)](9) and
      [UO2(terpy)2][OTf]2(10), respectively. The hydroxide compound
      [[UO2(OH)(terpy)]2][OTf]2(11) was obtained by hydrolysis in air of 1 in a mixture
      of acetonitrile and ethanol in the presence of terpyridine. The X-ray crystal
      structures of , and reveal a novel coordination geometry for the uranyl ion, the
      uranium atom being in a rhombohedral environment; the six coordinating ligands
      atoms of the [UO2]2+ ion are separated into two parallel and staggered
      equilateral triangles and the UO2 axis is perpendicular to these triangles,
      passing through their centre. The structures of the mono(terpy) complexes 9 and
      11 show the uranium atoms in a distorted pentagonal bipyramidal configuration
      with the nitrogen atom of the central pyridine ring of the terpy ligand
      significantly displaced from the equatorial plane.

PMID- 15514771
TI  - Synthesis, characterization and antioxidant activity of new copper(I) complexes
      of scorpionate and water soluble phosphane ligands.
AB  - New copper(I) complexes have been synthesised from the reaction of CuCl with
      potassium hydrotris(4-bromo-1H-pyrazol-1-yl)borate, KTp4Br or lithium bis(3,5
      dimethylpyrazol-1-yl)acetate, Li[L2CO2] ligands and 4- or 2
      (diphenylphosphane)benzoic acid or tris(m-sulfonatophenyl)posphine trisodium salt
      (TPPTS) coligands. The complexes obtained have been characterized by elemental
      analyses and FT-IR in the solid state, and by NMR (1H and 31P[1H]) and
      electrospray mass spectrometry (ESI-MS) in solution. Single crystal structural
      characterisation was undertaken for the [Cu[PPh2(4-C6H4COOH)](Tp4Br)] derivative,
      an interesting dimeric supramolecular assembly. A chemiluminescence study has
      demonstrated the superoxide scavenging activity of these new copper complexes.
      The Comet assay was used to evaluate the impairment of DNA in rat epithelial
      cells exposed to different reactive nitrogen species. In addition, the same
      complexes were included in this study to determine their efficacy as antioxidants
      in mitigating oxidative DNA damage. The parameter tail moment, used as an index
      of DNA damage, showed that the complex [Cu[PPh2(4-C6H4COOH)](Tp4Br)] remarkably
      inhibited DNA strand breaks induced by the different nitrogen oxide species. The
      other copper complexes under study showed a different ability to reduce tail
      moment values depending on the type of RNOS donor used.

PMID- 15514773
TI  - Active site structure and redox processes of cytochrome c oxidase immobilised in
      a novel biomimetic lipid membrane on an electrode.
AB  - Membrane-bound cytochrome c oxidase was attached to an electrode via a His-tag
      linker and studied by surface enhanced resonance Raman spectroscopy,
      demonstrating intact redox site structures and electron transfer between the
      electrode and the immobilized enzyme.

PMID- 15514772
TI  - From group 13-group 13 donor-acceptor bonds to triple-decker cations.
AB  - Donor-acceptor bonding between group 13 elements seems counter-intuitive because
      one normally thinks of e.g. boron and aluminium compounds as classical Lewis
      acids. Indeed, many such compounds have achieved industrial prominence in this
      regard. Recently, however, it has become possible to stabilize these and other
      group 13 elements in the +1 oxidation state as opposed to the archetypical +3
      oxidation state. Moreover, it turns out that in the +1 oxidation state these
      species are excellent donors--hence the formation of these unprecedented donor
      acceptor bonds. The discovery of such bonds has led, albeit indirectly, to the
      development of triple-decker main group cations. This aspect is also covered in
      the review.

PMID- 15514774
TI  - Preparation of aqueous gel beads coated by lipid bilayers.
AB  - Novel giant liposome microcapsules have been fabricated based on aqueous gel
      cores encapsulated with a lipid bilayer. The method involves templating of lipid
      stabilised water-in-oil emulsions after gelling the aqueous phase with a suitable
      hydrocolloid.

PMID- 15514775
TI  - Metallaborane reaction chemistry. A facile and reversible dioxygen capture by a B
      frame-supported bimetallic: structure of [(PMe2Ph)4(O2)Pt2B10H10].
AB  - [(PMe2Ph)4Pt2B10H10] reversibly takes up atmospheric dioxygen to give the
      fluxional 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.

PMID- 15514776
TI  - Synchronous, time resolved, diffuse reflectance FT-IR, energy dispersive EXAFS
      (EDE) and mass spectrometric investigation of the behaviour of Rh catalysts
      during NO reduction by CO.
AB  - Synchronous, time resolved, infra-red, XAFS, and mass spectroscopies are
      simultaneously applied in situ to the investigation of the dynamic behaviour of
      Rh/Al2O3 catalysts during NO reduction by CO; NO conversion, and its kinetic
      character are closely correlated to the conversion of Rh(I)(predominantly
      RhI(CO)2) to Rh(0).

PMID- 15514777
TI  - Non-interpenetrating honeycomb-like 2D [6,3] network built by a novel trigonal
      metalloligand.
AB  - The combination of a novel trigonal metalloligand and linear linker affords the
      large non-interpenetrating honeycomb-like 2D [6,3] network in spite of the large
      hexagon lattice dimension.

PMID- 15514778
TI  - Photochemical regulation of the activity of an endonuclease BamHI using an
      azobenzene moiety incorporated site-selectively into the dimer interface.
AB  - Endonuclease BamHI mutants having an azophenylalanine residue in the dimer
      interface (azoAla-BamHI) were synthesized; while the activity was almost
      suppressed using trans-azoAla-BamHI, the cis-isomer generated with
      photoirradiation recovered its intrinsic activity.

PMID- 15514779
TI  - Synthesis of long Poly(dG).Poly(dC) DNA using enzymatic reaction.
AB  - Non-defect Poly(dG).Poly(dC) of 500 bp (170 nm) has been synthesized by using
      enzymatic reactions and was characterized by its UV spectrum, showing that
      conjugated pi-electrons between base pairs are spread over the DNA molecule
      suggesting the absence of structural defects.

PMID- 15514780
TI  - Octahedral metal clusters as building units in a neutral layered honeycomb
      network, [Zn(en)]2[Nb6Cl12(CN)6].
AB  - A polymeric hybrid cluster-based compound with a double-layered honeycomb
      framework built of octahedral niobium cyanochloride clusters and [Zn(en)]2+ metal
      complexes was designed and synthesized at room temperature, and structurally
      characterized by single crystal X-ray diffraction.

PMID- 15514781
TI  - A simulation of key aspects of a primary process in natural photosynthesis by a
      Langmuir-Blodgett film assembly.
AB  - An advanced Langmuir-Blodgett (LB) assembly designed to replicate the three key
      aspects (antenna, reaction center, and quinone pool) of a primary process in
      natural photosynthesis was successfully fabricated by alternate deposition of a
      mixed monolayer of an artificial reaction center and an antenna pigment and a
      pure bilayer of a second donor.

PMID- 15514782
TI  - Cobalt-mediated cyclotrimerisation of bis-alkynes and cyanamides.
AB  - CpCo(CO)2-mediated cyclotrimerisation of bis-alkynes and cyanamides provides
      multisubstituted 2-aminopyridines, including macrocyclic products, such as 22
      (50% yield).

PMID- 15514783
TI  - Novel Mg2SiO4 structures.
AB  - We describe the formation of novel, leaf-like Mg2SiO4 structures, via iodine
      vapour transport of magnesium onto quartz substrates.

PMID- 15514784
TI  - [PtMe(iPr3P)2]+: a Pt(II) complex with an agostic interaction that undergoes C-H
      activation.
AB  - The T-shaped Pt(II) complex [PtMe(iPr3P)2][1-H-closo-CB11Me11], which is
      stabilised by an agostic interaction, undergoes acid-catalysed intramolecular C-H
      activation in the presence of THF to afford cyclometallated
      [Pt(THF)(iPr3P)(iPr2PCHMeCH2)][1-H-closo-CB11Me11].

PMID- 15514785
TI  - Multiple hydrogen bonds. Mass spectra of hydrogen bonded heterodimers. A
      comparison of ESI- and REMPI-ReTOF-MS.
AB  - Resonance enhanced multi-photon ionization-reflectron time of flight mass
      spectrometry is the analytical method of choice to observe hydrogen bonded
      supramolecules in the gas phase when protonation of basic centers competes with
      cluster formation.

PMID- 15514786
TI  - Biosynthesis of hydroxydiphenylacetylene by regiospecific monooxygenation.
AB  - Bacterial monooxygenase enzymes catalyze a regiospecific single-step
      hydroxylation of diphenylacetylene to yield meta- and para
      hydroxydiphenylacetylene.

PMID- 15514787
TI  - A synthesis of (+/-)-sparteine.
AB  - (+/-)-Sparteine has been synthesised with stereochemistry controlled in such a
      way as to make the route amenable to an efficient synthesis of either enantiomer.

PMID- 15514788
TI  - Substrate binding and the presence of ferredoxin affect the redox properties of
      the soluble plant Delta9-18:0-acyl carrier protein desaturase.
AB  - Substrate-free Delta9-18:0-acyl carrier protein desaturase (abbreviated to
      Des)[E.C. # 1.14.99.6] was 2-electron reduced with E'0=-0.03 +-0.01 V; the
      presence of spinach ferredoxin (SpFd) induces an additional 1-electron reduction
      wave at E'0=-0.21 +-0.02 V, which shifts by 0.106 V upon substrate binding.

PMID- 15514789
TI  - Enantio- and diastereocontrol in intermolecular cyclopropanation reaction of
      styrene catalyzed by dirhodium(II) complexes with bulky ortho-metalated aryl
      phosphines.
AB  - Enantiomerically pure dirhodium(II) complexes with ortho-metalated p-substituted
      aryl phosphines have been shown to be enantio- and diastereoselective in the
      cyclopropanation of styrene by ethyl diazoacetate. Enantioselectivities up to 91%
      and diastereoselectivities up to 90% are observed for ethyl cis-2
      phenylcyclopropanecarboxylate.

PMID- 15514790
TI  - Self-organisation in P-substituted guanidines leading to solution-state
      isomerisation.
AB  - Different isomeric forms of the amidine unit have been identified in
      Ph2P(E)C[NR'][NHR'] (E = S, Se; R' = iPr, Cy), using both solid- and solution
      state techniques.

PMID- 15514791
TI  - Intein-mediated purification of a recombinantly expressed peptide.
AB  - A 26 amino acid peptide has successfully been purified via recombinant expression
      as an intein fusion protein accompanied by cleavage without the need for any
      exogenous proteases or cofactors, thus offering a practical, inexpensive approach
      to produce isotopically labelled peptides.

PMID- 15514792
TI  - Facile fabrication and characterization of hierarchically porous calcium
      carbonate microspheres.
AB  - Higher-order porous calcite microspheres exhibiting high specific surface areas,
      unusual morphologies and textures were fabricated by a simple precipitation
      reaction of CaCO3 in the presence of PSMA as a crystal modifier.

PMID- 15514793
TI  - Development of highly active and selective novel Pd based acetoxylation catalysts
      and prevention of catalyst deactivation by Bi modification.
AB  - A first approach to successful prevention of catalyst deactivation while
      simultaneously achieving extremely high selectivity of benzyl acetate (> or =
      95%) at significantly high toluene conversion (> 70%) by gas phase acetoxylation
      over novel Pd-Sb-Bi/TiO2 catalysts.

PMID- 15514794
TI  - Assembly of a photoreactive coordination polymer containing rectangular grids.
AB  - We describe the synthesis, crystal structure and solid state reactivity of
      cadmium fumarate dihydrate, which is made up of planar H-bonded metal-organic
      layers and undergoes, upon irradiation, a topochemical [2 + 2] cycloaddition
      reaction.

PMID- 15514795
TI  - Oligo(fluorenyleneethynylenegermylene)s and their metallopolymers.
AB  - Oligo(fluorenyleneethynylenegermylene)s and their polyplatinynes are synthesized
      and photophysically characterized; inclusion of heavy germylene bridges greatly
      boosts the phosphorescence decay rate in metallopolymers.

PMID- 15514796
TI  - Isolation and characterisation of the mixed-metal alkyl amide [(TMEDA)Na(mu
      Bu)(mu-TMP)Mg(TMP)], an unexpected chelate-trapped intermediate in the formation
      of inverse crowns.
AB  - Only two-fold amination occurs when 3 molar equivalents of TMPH are offered to a
      1:1 BuNa-Bu2Mg mixture; adding TMEDA gives the mixed alkyl amide [(TMEDA)Na(mu
      Bu)(mu-TMP)Mg(TMP)], which itself affords the phenyl-bridged analogue when
      reacted with benzene.

PMID- 15514797
TI  - A simple visual assay based on small molecule hydrogels for detecting inhibitors
      of enzymes.
AB  - Here we report a simple approach to develop assays based on the hydrogelation of
      small molecules for quick detecting inhibitors of enzymes.

PMID- 15514798
TI  - Periodic mesoporous phenylenesilicas with ether or sulfide hinge groups--a new
      class of PMOs with ligand channels.
AB  - A new class of periodic mesoporous organosilicas (PMOs) with 4-phenyl ether and 4
      phenyl sulfide bridge-bonded silsesquioxanes integrated into the pore walls to
      create ligand channels have been synthesized using inorganic salt-assisted self
      assembly directed by a supramolecular polyoxyethylene (10) stearyl ether (Brij
      76) template.

PMID- 15514799
TI  - HfMoSb4, the first nonmetallic early transition metal antimonide.
AB  - HfMoSb4, isostructural with the isoelectronic NbSb2, exhibits nonmetallic
      properties, as predicted via electronic structure calculations made before the
      actual discovery of HfMoSb4.

PMID- 15514800
TI  - Dearomatising rearrangements of lithiated thiophenecarboxamides.
AB  - Thiophene-3-carboxamides bearing allyl or benzyl substituents at nitrogen undergo
      dearomatising cyclisation on treatment with LDA. Rearrangements transform the
      dearomatised products into pyrrolinones, azepinones or partially saturated
      azepinothiophenes.

PMID- 15514801
TI  - m-Terphenyl thiols: rigid and bulky molecules for the formation of bioactive self
      assembled monolayers on gold.
AB  - The m-terphenyl 4-mercaptomethyl-2,6-diphenylbenzoic acid (3), was prepared and
      shown to form omega-carboxyl terminated self-assembled monolayers (SAMs) on gold
      with high surface pKa(10.1 +/- 0.2) and low density favourable for the binding of
      biological macromolecules.

PMID- 15514802
TI  - Synthesis and unprecedented oxidation of a cationic Sb-analogue of an Arduengo's
      carbene.
AB  - 2-chloro-1,3,2-diazastibolenes react with Lewis acids either via Sb-Cl cleavage
      to yield stable Sb-analogues of an N-heterocyclic carbene, or via an
      unprecedented oxidative fragmentation to give a diazadiene-SbCl3 complex.

PMID- 15514803
TI  - Sensitivity increase in molecular recognition by decrease of the sensing particle
      size and by increase of the receptor binding site--a case with chemomechanical
      polymers.
AB  - For the first time it is shown that diminishing the particle size of a
      chemomechanical polymer leads to a dramatic sensitivity increase, with a large
      response triggered e.g. by action of external AMP; as illustrated with
      carbohydrate model complexes in solution, the necessary high binding affinity can
      be achieved by providing an excess of recognition units in one of the partners.

PMID- 15514804
TI  - Shape of CeO2 nanoparticles using simulated amorphisation and recrystallisation.
AB  - Evolutionary simulation has been used to generate full atomistic models for CeO2
      nanoparticles, which comprise [100]-truncated [111] octahedra in accord with
      experiments.

PMID- 15514805
TI  - A new series of sodium cobalt oxyhydrates.
AB  - We report a new series of sodium cobalt oxyhydrates that contains the same two
      dimensional building blocks as superconducting NaxCoO2.yH2O. The absence of
      superconductivity emphasises the importance of the CoO2 stacking arrangement on
      the resultant electronic properties.

PMID- 15514806
TI  - Direct conversion of iron stearate into magnetic Fe and Fe3C nanocrystals
      encapsulated in polyhedral graphite cages.
AB  - We report a direct salt-conversion approach for large-scale synthesis of carbon
      encapsulated magnetic Fe and Fe3C nanoparticles.

PMID- 15514807
TI  - Polysulfones: solid organic catalysts for the chemoselective cleavage of methyl
      substituted allyl ethers under neutral conditions.
AB  - The solid polysulfone made of SO2 and methylidenecyclopentane catalyzes the
      cleavage of methyl-substituted allyl ethers and liberates the corresponding
      alcohols.

PMID- 15514808
TI  - Structurally diverse Rh(I) and Mn(I) complexes derived from the new ambidentate
      indene ligand, (1-[iPr2P(S)]-2-[NMe2])C9H6.
AB  - A new indene-based ligand featuring pendant phosphine sulfide and amine donor
      fragments has been developed; Rh(I) coordinates to the neutral form of the ligand
      in a kappa2-[N,S] fashion, while the anionic form of the ligand binds Rh(I) and
      Mn(I) in kappa2-[C,S] and eta5 modes, respectively.

PMID- 15514809
TI  - BINOL catalyzed enantioselective addition of titanium phenylacetylide to aromatic
      ketones.
AB  - An enantioselective addition of titanium phenylacetylide to ketones, promoted by
      BINOL, is described; this new enantioselective protocol gives high enantiomeric
      excess (up to 90% ee) with aromatic ketones using a simple procedure without
      pyrophoric or expensive reagents.

PMID- 15514810
TI  - L-proline catalyzed asymmetric transfer aldol reaction between diacetone alcohol
      and aldehydes.
AB  - We demonstrate for the first time, L-proline as a chiral catalyst for transfer
      aldol reaction between aldehydes and diacetone alcohol.

PMID- 15514811
TI  - A facile synthesis of single-crystal mullite nanobelts.
AB  - Single-crystal mullite nanobelts were prepared by a simple sol-gel method using
      WO3 as a catalyst. The nanobelts are straight and uniform with a width of 200 nm
      and length of 3-4 microm.

PMID- 15514812
TI  - A new organic superconductor beta-(meso-DMBEDT-TTF)2PF6.
AB  - A newly synthesized donor meso-DMBEDT-TTF [DMBEDT-TTF = 2-(5,6-dihydro-1,3
      dithiolo[4,5-b][1,4]dithiin-2-ylidene)-5,6-dihydro-5,6-dimethyl-1,3-dithiolo[4,5
      b][1,4]dithiin] afforded a superconducting salt beta-(meso-DMBEDT-TTF)2PF6, with
      a transition temperature at 4.3 K (onset) under a hydrostatic pressure of 4.0
      kbar.

PMID- 15514813
TI  - Silicon-assisted propargylic transfer to aldehydes.
AB  - A new and efficient method of obtaining homopropargylic alcohols via
      homopropargylic transfer from the allenic alcohol to various aldehydes in the
      presence of Lewis acid catalysts is described; stereochemical studies have shown
      that this process is the first oxonium [3,3]-sigmatropic rearrangement of an
      allenic alcohol to a homopropargylic alcohol in the presence of aldehydes and
      Lewis acid.

PMID- 15514814
TI  - Bond energy, aromatic stabilization energy and strain in IPR fullerenes.
AB  - Various models applied to DFT structures and energies of 2-D and 3-D aromatic
      molecules shed new light on the effects of strain and aromaticity in these
      systems. The cyclic pi electron delocalisation does not stabilize the fullerene
      C60 formation; and 5-6 and 6-6 CC bonds have near-identical bond stretch
      potentials.

PMID- 15514815
TI  - Thin Pd membrane prepared on macroporous stainless steel tube filter by an in
      situ multi-dimensional plating mechanism.
AB  - The big surface pores of a porous stainless steel (PSS) tube filter with marked
      roughness were jammed with aluminium hydroxide gel by a combination of ultrasonic
      vibration and vacuum suction, then a thin dense Pd membrane (6 microm) was plated
      in-situ on this pre-jammed filter by a multi-dimensional plating mechanism; after
      recovering the substrate pores by high temperature treatment, higher H2 permeance
      and complete H2 selectivity were obtained.

PMID- 15514816
TI  - Stereospecific peptide folds. A rationally designed molecular bracelet.
AB  - A canonical planar beta-hairpin peptide, stereochemically reengineered into a
      semicircular bracelet type motif by L-to-D stereochemical inversion in two pairs
      of its cross-strand neighbor residues, displays protein like ordering including
      two-state behavior in H2O, which is unusual for a small peptide of this size.

PMID- 15514817
TI  - Synthesis and properties of rhenium tricarbonyl complex bearing N-fused
      tetraphenylporphyrin ligand.
AB  - An N-fused porphyrin rhenium complex was synthesized by the thermal reaction of
      an N-confused porphyrin with Re2(CO)10 and its structure was determined by X-ray
      crystallographic analysis.

PMID- 15514818
TI  - The first tandem double palladium-catalyzed aminations: synthesis of dipyrido[1,2
      a:3',2'-d]imidazole and its benzo- and aza-analogues.
AB  - A new strategy for the synthesis of the title compounds via a regio- and
      chemoselective one-pot inter- and intramolecular Buchwald-Hartwig amination of 2
      chloro-3-iodopyridine with aminoazines and -diazines is reported.

PMID- 15514819
TI  - Site-specific oxidative cleavage of DNA by metallosalen-DNA conjugates.
AB  - Ni-salen-DNA conjugates, prepared by template-directed synthesis, targeted
      oxidative adduct formation and strand scission at deoxyguanosine sites in
      complementary DNA strands of Watson-Crick duplexes.

PMID- 15514820
TI  - Construction of building-blocks for polyether synthesis using sequential
      catalytic ring-closing enyne and cross metathesis.
AB  - Highly functionalised six- and seven-membered cyclic ethers bearing a variety of
      side chains have been synthesised using ring-closing enyne metathesis and
      subsequent cross metathesis of the intermediate diene; one-pot enyne and cross
      metathesis has also been accomplished, allowing ring construction and side chain
      introduction to be performed in a single operation.

PMID- 15514821
TI  - Electrogeneration of a biotinylated poly(pyrrole-ruthenium(II)) film for the
      construction of photoelectrochemical immunosensor.
AB  - A biotinylated photosensitive polymer was electrogenerated from on a ruthenium
      complex bearing biotin and pyrrole groups; the resulting polypyrrolic film
      allowed the bioaffine immobilisation of avidin and biotinylated cholera toxin and
      the photoelectrochemical detection of the corresponding antibody.

PMID- 15514822
TI  - Novel formation and use of a Nicholas carbocation in the synthesis of highly
      substituted tetrahydrofurans.
AB  - The first formation of a Nicholas carbocation through cleavage of a carbon-carbon
      sigma bond has allowed the preparation of highly substituted tetrahydrofurans in
      a formal dipolar cycloaddition reaction.

PMID- 15514823
TI  - Structural defects cause TiO2-based photocatalysts to be active in visible light.
AB  - Oxidation of TiO or Ti2O3 led to the formation of TiO2 with activity in visible
      light much higher than when TiN was used as a precursor, pointing out the
      importance of oxygen defects/vacancies for extension of activity of TiO2 into the
      visible region.

PMID- 15514824
TI  - A new synthetic entry to phosphinophosphinidene complexes. Synthesis and
      structural characterisation of the first side-on bonded and the first terminally
      bonded phosphinophosphinidene zirconium complexes [mu-(1,2:2-eta
      tBu2P=P)[Zr(Cl)Cp2]2] and [[Zr(PPhMe2)Cp2](eta1)-P-PtBu2)].
AB  - The reactions of lithiated diphosphanes with transition metal chlorides
      constitute a new general entry to phosphinophosphinidene complexes: the reaction
      of Cp2ZrCl2(Cp = C5H5) with tBu2P-P(SiMe3)Li (molar ratio approximately 1:1)
      yields [mu-(1,2:2-eta-tBu2P=P)[Zr(Cl)Cp2]2]; the reaction of Cp2ZrCl2 with tBu2P
      P(SiMe3)Li (molar ratio approximately 1:2) and an excess of PPhMe2 in DME yields
      the first terminally bonded phosphinophosphinidene complex, [[Zr(PPhMe2)Cp2](eta1
      P-PtBu2)].

PMID- 15514825
TI  - Enhancement of alpha-oxygen formation and N2O decomposition on Fe/ZSM-5 catalysts
      by extraframework Al.
AB  - The concentration of alpha-oxygen which can oxidize methane to methanol and
      benzene to phenol at RT, increases linearly with the amount of introduced
      extraframework Al on Fe/ZSM-5 catalysts prepared by solid-state exchange of FeCl3
      and AlCl3 with H-ZSM-5.

PMID- 15514826
TI  - Intramolecular nucleophilic carbonyl trapping of alpha-ketenyl radicals by an
      amino group.
AB  - Free-radical carbonylation of omega-alkynylamines with tributyltin hydride gives
      a mixture of alpha-methylene lactams and alpha-stannylmethylene lactams.
      Nucleophilic addition of an internal amino group to the carbonyl group of alpha
      ketenyl radicals is proposed as the cyclization step. The subsequent unusual 1,4
      H shift from the resulting 1-hydroxyallyl radical, followed by elimination of the
      beta-tributyltin radical leads to the formation of alpha-methylene lactams.

PMID- 15514827
TI  - Synthesis of core-shell polyurethane-urea nanoparticles containing 4,4'
      methylenedi-p-phenyl diisocyanate and isophorone diisocyanate by self-assembled
      neutralization emulsification.
AB  - Polyurethane-urea nanoparticles containing 4,4'-methylenedi-p-phenyl diisocyanate
      and isophorone diisocyanate were synthesized by utilizing self-assembled
      neutralization emulsification and their particle morphology could be controlled.

PMID- 15514828
TI  - Novel C-C bond formation through addition of ammonium ylides to arylaldehydes: a
      facile approach to beta-aryl-beta-hydroxy alpha-amino acid frameworks.
AB  - Ammonium ylides generated in situ from [small alpha]-diazo esters and amines in
      the presence of catalytic Rh2(OAc)4, undergo an aldol-type reaction with
      aldehydes affording highly substituted amino acid frameworks in a convergent,
      three-component reaction.

PMID- 15514829
TI  - Aziridine sulfides and disulfides as catalysts for the enantioselective addition
      of diethylzinc to aldehydes.
AB  - Chiral aziridine sulfides and disulfides were synthesized from readily available
      and inexpensive R-cysteine by a Mitsunobu reaction; their application in the
      addition of diethylzinc to aldehydes provides secondary alcohols with up to 99%
      ee and S-configuration.

PMID- 15514830
TI  - Enhanced photoluminescence from poly(phenylene vinylene):dendrimer
      polyelectrolyte assemblies in solution.
AB  - Poly(2,5-methoxy-propyloxy sulfonate phenylene vinylene)(MPS-PPV) and DAB-Am-16,
      a generation 3.0 polypropylenimine hexadecamine dendrimer (DAB), are shown to
      form a tunable photoresponsive polyelectrolyte assembly in aqueous solution with
      an enhanced emission signal of up to 18-times that of MPS-PPV alone.

PMID- 15514831
TI  - Chiral discrimination within disordered adlayers on metal surfaces.
AB  - Using a novel non-linear optical technique enantiomeric excess within a
      translationally disordered overlayer on a metal surface has been monitored for
      the first time.

PMID- 15514832
TI  - Enantioselective synthesis of allenyl carbinols by the CBS reduction in
      nitroethane: dramatic solvent effect for reactivity and enantioselectivity.
AB  - Dramatic solvent effect of nitroethane was observed in the catalytic asymmetric
      reductions of allenyl ketones and alpha,beta-ynones using the oxazaborolidine
      cayalyst to yield the corresponding alcohols in high levels of
      enantioselectivity.

PMID- 15514833
TI  - Mesostructured SBA-3 silica containing Reichardt's dye as an optical ammonia
      sensor.
AB  - Mesostructured SBA-3 silica containing Reichardt's dye is shown to give a
      reversible optical response to gaseous ammonia, with a response time of a few
      seconds and an intensity proportional to the ammonia partial pressure, which are
      desirable properties for gas sensing.

PMID- 15514834
TI  - Molecular sieving platinum nanoparticle catalysts kinetically frozen in
      nanoporous carbon.
AB  - Highly active shape selective catalysts with excellent thermal stability are
      synthesized by entrapping well dispersed platinum nanoparticles in a polyfurfuryl
      alcohol derived nanoporous carbon matrix; these nanocomposites are excellent
      candidates for new catalytic applications including fuel cells, pharmaceutical
      synthesis and biomass conversion.

PMID- 15514835
TI  - Dual-functionalised ionic liquids: synthesis and characterisation of imidazolium
      salts with a nitrile-functionalised anion.
AB  - A series of 'dual-functionalised' ionic liquids, comprising imidazolium cations
      with various functionalities and the nitrile functionalised anion
      [CH3CH(BF3)CH2CN]- have been prepared; some exhibit very low viscosities-a highly
      valuable property in many applications.

PMID- 15514836
TI  - Diastereoselective conjugate reduction with samarium diiodide: asymmetric
      synthesis of methyl (2S,3R)-N-acetyl-2-amino-2,3-dideuterio-3-phenylpropionate.
AB  - A highly diastereoselective conjugate reduction using SmI2 and D2O has been
      demonstrated on a homochiral benzylidene diketopiperazine template, giving methyl
      (2S,3R)-N-acetyl-2-amino-2,3-dideuterio-3-phenylpropionate in 93% de and 90% ee
      after deprotection, hydrolysis and N-acetylation.

PMID- 15514838
TI  - A cascade enyne/ring closing metathesis approach to angularly fused
      dioxatriquinanes.
AB  - An expedient and first tandem enyne/ring closing metathesis approach on a sugar
      furanose template leading to a novel angularly fused dioxa-triquinane is
      described here.

PMID- 15514837
TI  - Stereoelective polymerization of D,L-lactide using N-heterocyclic carbene based
      compounds.
AB  - A new Zn alkoxide catalyst supported by an N-heterocyclic carbene rapidly
      polymerizes D,L-lactide (D,L-LA) to heterotactic enriched poly(lactide)(PLA),
      while the free carbene and analogs instead yield highly isotactic enriched PLA.

PMID- 15514839
TI  - Solvent-dependent aggregation of a water-soluble poly(fluorene) controls energy
      transfer to chromophore-labeled DNA.
AB  - The solvent-dependent aggregation properties of a water-soluble cationic
      poly(fluorene) were studied and used to control fluorescence resonance energy
      transfer to Texas Red-labeled DNA.

PMID- 15514840
TI  - Protein-resistant monolayers prepared by hydrosilylation of alpha-oligo(ethylene
      glycol)-omega-alkenes on hydrogen-terminated silicon (111) surfaces.
AB  - Atomically flat, homogeneous, and protein-resistant monolayers can be readily
      prepared on H-Si(111) surfaces by photo-induced hydrosilylation of alpha
      oligo(ethylene glycol)-omega-alkenes.

PMID- 15514841
TI  - Self-aggregated phosphorescent platinum(II) polymeric material from modified
      poly(4-vinylpyridine).
AB  - A solvochromic material made from incorporation of photoluminescent
      Pt(II)([formula: see text]) moieties into commercially available homopolymer
      poly(4-vinylpyridine) exhibits different emission energies, due to different
      degrees of self-aggregation in various solvents and as thin film upon exposure to
      vapour of different volatile organic compounds (VOC); self-aggregation enables
      intra- and intermolecular interactions arising from pi-stacking of the
      Pt([formula: see text]) moieties, which is affected by medium polarity.

PMID- 15514842
TI  - Modular synthesis of formamidines and their formation of stable organogels.
AB  - An improvement in the practical aspects of formamidine synthesis has resulted in
      the discovery of a class of compounds which produce organogels in protic
      solvents, presumably through intermolecular hydrogen bonding and pi-pi stacking
      interactions.

PMID- 15514844
TI  - Conus peptides--a rich pharmaceutical treasure.
AB  - Marine predatory cone snails (genus Conus) with over 500 species represent what
      is arguably the largest single genus of marine animals alive today. All Conus are
      venomous and utilize a complex mixture of Conus peptides to capture their preys
      and for other biological purposes. Each component of Conus peptides selectively
      targets a specific subtype of ion channels, neurotransmitter receptors or
      transporters. Owing to their diversity, more than 50,000 distinct active peptides
      are theoretically estimated in Conus venoms. These diversified toxins are
      generally categorized into several superfamilies and/or families based on their
      characteristic arrangements of cysteine residues and pharmacological actions.
      Some mechanisms underlying the remarkable diversity of Conus peptides have been
      postulated: the distinctive gene structure, gene duplication and/or allelic
      selection, genus speciation, and sophisticated expression pattern and post
      translational modification of these peptides. Due to their highly pharmacological
      potency and target selectivity, Conus peptides have attracted extensive attention
      with their potentials to be developed as new research tools in neuroscience field
      and as novel medications in clinic for pain, epilepsy and other neuropathic
      disorders. Several instructive lessons for our drug development could be also
      learnt from these neuropharmacological "expertises". Conus peptides comprise a
      rich resource for neuropharmacologists, and most of them await to be explored.

PMID- 15514845
TI  - Dynamics of primary events in the photocycle of excited bacteriorhodopsin.
AB  - Transient dynamic behavior of the excited bacteriorhodopsin (BR), which was
      isolated from the strain H. salinarum, was studied at excitation wavelength from
      585 to 639 nm. With the one-color femtosecond (fs) pump-probe technique, we
      revealed the primary events in BR's photocycle that took place in an ultrafast
      time scale. From the analysis of the decay components of the dynamical traces, it
      was evident that the isomerization of the retinal chromophore in BR and the
      intermediate J's formation occurred within 500 fs. BR exhibited pH-dependent
      dynamical behaviors. When the medium pH was between 5 and 9, the BR ultrafast
      dynamics has no obvious change. In contrast, the dynamical curves were obviously
      affected when the pH was out of that region.

PMID- 15514846
TI  - A mathematical model of baculovirus infection on insect cells at low multiplicity
      of infection.
AB  - The expression efficiency of the insect cells-baculovirus system used for
      insecticidal virus production and the expression of medically useful foreign
      genes is closely related with the dynamics of infection. The present studies
      develop a model of the dynamic process of insect cell infection with baculovirus
      at low multiplicity of infection (MOI), which is based on the multi-infection
      cycles of insect cell infection at low MOI described. A mathematical model for
      the amount of viruses released from primary infected cells and the amount of free
      viruses before secondary infected cells release viruses has been developed.
      Comparison of the simulation results with the experimental data confirms
      qualitatively that this model is highly reasonable before secondary infected
      cells release viruses. This model is considered as a base for further modeling
      the entire complicated infection process.

PMID- 15514847
TI  - Shock waves increase T-cell proliferation or IL-2 expression by activating p38
      MAP kinase.
AB  - Shock waves were elicited by transient pressure disturbances, which could be used
      to treat musculoskeletal disorders. In present studies, we investigated whether
      the low-density shock waves (LDSWs), which are able to damage plasma membrane
      without impairing the vimentin or other organelles, might augment T-cell
      proliferation as well as IL-2 expression, and if mitogen activated protein kinase
      p38 (p38 MAPK) might be an underlying mechanism through which the LDSWs enhanced
      T-cell function. We found that the LDSWs increased activation of p38 MAPK in
      Jurkat T cells. The LDSWs alone didn't result in the T-cell proliferation and IL
      2 expression. However, in combination with other stimuli, LDSWs could augment the
      T-cell proliferation and IL-2 expression. Inhibition of p38 MAPK using SB203580
      reduced the stimulatory effects of the LDSWs, which indicated that the LDSWs
      enhanced IL-2 expression through a mechanism that involved p38 MAPK activation.
      We concluded that the p38 MAPK activation played a key role in the regulation of
      T cells function by the LDSWs.

PMID- 15514848
TI  - Suppression of bcl-2 gene by RNA interference increases chemosensitivity to
      cisplatin in nasopharyngeal carcinoma cell line CNE1.
AB  - To explore the effect of suppressing BCL-2 expression using RNA interference
      (RNAi) technique in nasopharyngeal carcinoma cell line CNE1. CNE1 cell lines
      stably expressing shRNAs targeted bcl-2 and GL3 gene were established and gene
      expression inhibition was assessed by Western blotting analysis. The effect of
      suppressing bcl-2 by RNAi on cell growth was studied, the apoptosis induction and
      the sensitization of CNE1 cells to cisplatin were quantified by MTT assays and
      flow cytometry. The results showed that: stable transfection of CNE1 cells with
      vectors expressing shRNAs against bcl-2 decreased the expression of BCL-2
      protein; suppression of BCL-2 expression did not affect cell proliferation but
      could increase the chemosensitivity to cisplatin in CNE1 cells. This will help
      physicians to make some clinical trials of gene therapy on nasopharyngeal
      carcinoma by RNAi.

PMID- 15514849
TI  - Expression, purification and sublocalization of SARS-CoV nucleocapsid protein in
      insect cells.
AB  - The causative agent of severe acute respiratory syndrome (SARS) is a previously
      unidentified coronavirus, SARS-CoV. The nucleocapsid (N) protein of SARS-CoV is a
      major viral protein recognized by acute and early convalescent sera from SARS
      patients. To facilitate the studies on the function and structure of the N
      protein, this report describe the expression and purification of recombinant SARS
      CoV N protein using the baculovirus expression system. Recombinant hexa-histidine
      tagged N protein with a molecular mass of 47 kD was produced in insect cells.
      Recombinant N protein was purified to near homogeneity by Ni2+-NTA affinity
      chromatography. In addition, we examined the subcellular localization of the N
      protein by confocal microscopy in Trichoplusia ni BT1 Tn 5B1-4 cells infected
      with recombinant baculovirus. The N protein was found localized in the cytoplasm
      as well as in the nucleolus. The purified recombinant N protein can be used in
      further functional study of SARS-CoV.

PMID- 15514850
TI  - Intein-mediated rapid purification of recombinant human pituitary adenylate
      cyclase activating polypeptide.
AB  - In order to obtain the recombinant human PACAP efficiently by intein-mediated
      single column purification, a gene encoding human PACAP was synthesized and
      cloned into Escherichia coli expression vector pKYB. The recombinant vector pKY
      PAC was transferred into E. coli ER2566 cells and the target protein was over
      expressed as a fusion to the N-terminus of a self-cleavable affinity tag. After
      the PACAP-intein-CBD fusion protein was purified by chitin-affinity
      chromatography, the self-cleavage activity of the intein was induced by DTT and
      the rhPACAP was released from the chitin-bound intein tag. The activity of the
      rhPACAP to stimulate cyclic AMP accumulation was detected using the human
      pancreas carcinoma cells SW1990. Twenty-two milligrams of rhPACAP with the purity
      over 98% was obtained by single column purification from 1 liter of induced
      culture. The preliminary biological assay indicated that the rhPACAP, which has
      an extra Met at its N-terminus compared with the native human PACAP, had the
      similar activity of stimulating cAMP accumulation with the standard PACAP38 in
      the SW1990 cells. A new efficient production procedure of the active recombinant
      human PACAP was established.

PMID- 15514851
TI  - Inhibitory effect of TCCE on CCl4-induced overexpression of IL-6 in acute liver
      injury.
AB  - Terminalia catappa L. leaves have been shown to protect against acute liver
      injury produced by some hepatotoxicants, but the active components and mechanisms
      are not clear. This study was designed to characterize the protective effects of
      the chloroform fraction of the ethanol extract of T. catappa leaves (TCCE)
      against carbon tetrachloride (CCl4)-induced hepatotoxicity in mice, and analyze
      the changes in expression level of interleukin-6 (IL-6) in the process. It was
      found that TCCE pretreatment (10 or 30 mg/kg, ig) protected mice from CCl4
      toxicity, as evidenced by the reversed alterations in serum alanine
      aminotransferase (sALT) and serum aspartate aminotransferase (sAST) activities.
      Additionally liver tissues were subjected to RT-PCR, Western blot and
      immunohistochemistry to analyze changes in IL-6 expression. It was found that
      TCCE markedly suppressed the CCl4-induced over-transcription of IL-6 gene.
      Consistent with the result, the expression of IL-6 protein was also blocked by
      TCCE in CCl4-stimulated mice, especially in the area around central vein on liver
      tissue section. In conclusion, TCCE is effective in protecting mice from the
      hepatotoxicity produced by CCl4, and the mechanisms underlying its protective
      effects may be related to the inhibition on the overexpression of IL-6 mainly
      around terminal hepatic vein.

PMID- 15514852
TI  - Accumulation of pathogenesis-related type-5 like proteins in phytoplasma-infected
      garland chrysanthemum Chrysanthemum coronarium.
AB  - Soluble proteins extracted from leaves, apical shoots, axillary shoots, and stems
      of garland chrysanthemum plants infected by onion yellows phytoplasma were
      analyzed by two-dimensional gel electrophoresis. Computerized matching analysis
      revealed that at least six soluble proteins were accumulated specifically in
      phytoplasma-infected garland chrysanthemum. N-terminal amino acids sequences of
      these soluble proteins, determined by Edman degradation, shared high sequence
      similarities with those of pathogenesis-related type-5 (PR-5) proteins such as
      tobacco thaumatin-like protein. Accumulation of these six proteins was also found
      in garland chrysanthemum plants infected by other phytoplasmas. These results
      demonstrate that phytoplasmal infection induces the accumulation of PR-5 like
      proteins in garland chrysanthemum plants.

PMID- 15514853
TI  - Isolation and characterization of photosystem II of Porphyra yezoensis Ueda.
AB  - The thylakoid membranes were isolated and purified from gametophyte of Porphyra
      yezoensis Ueda (P. yezoensis) by sucrose density gradient ultracentrifugation.
      After P. yezoensis gametophyte thylakoid membranes were solubilized with SDS, the
      photosystem II (PSII) particles were isolated and purified. The activity of PSII
      particles was determined with DCIP (2,6-dichloroindophenol) photoreduction
      reaction. The composition of purified PSII particles was detected by SDS-PAGE. As
      a result, seven proteins including 55 kD protein, 47 kD protein, 43 kD protein,
      33 kD protein, 31 kD protein, 29 kD protein, and 18 kD protein were found.
      Compared with PSII particles of higher plants and other algae, they were
      identified as D1/D2 complex, CP47, CP43, 33 kD protein, D1, D2 and cyt c-550
      respectively. Besides, other three new proteins of 20 kD, 16 kD and 14 kD
      respectively were found. Among these extrinsic proteins, the 16 kD and 14 kD
      proteins had not been reported previously, and the 20 kD protein was found for
      the first time in multicellular red algae.

PMID- 15514854
TI  - [The protocol and design of etiological study.].
AB  - An accurate diagnosis and effective treatment are based on deep insight into the
      etiology of a disease. With the development of society, some diseases have been
      controlled successfully since their cause and mechanism are well understood, but
      a few more new diseases arose. It is necessary to study them by a proper design
      for establishing a correct diagnosis and effective therapy. The basic knowledge
      is rather important for clinicians. This paper introduces the commonly used
      protocol and design of etiological study with an example of the study on caries
      etiology.

PMID- 15514855
TI  - [The effect of premolar extractions on Bolton index.].
AB  - PURPOSE: The purpose of this study is to investigate the effect of premolar
      extractions on Bolton index. METHODS: 213 plaster casts were divided into Bolton
      big, normal and small groups according to Bolton normal value and one standard
      deviation. Bolton overall ratios and number of patients in each group were
      measured and compared between parameters before and after hypothetical premolar
      extractions. RESULTS: The Bolton overall ratios in each group were smaller after
      premolar extractions than those before extractions. Part of patients in the
      Bolton normal group and big group were changed into Bolton small group and normal
      group after premolar extractions, respectively. CONCLUSION: The Bolton overall
      ratios decreased after premolar extractions.

PMID- 15514856
TI  - [The effects of feeding methods on deciduous caries.].
AB  - PURPOSE: The goal of this study was to explore the relationship between feeding
      methods and deciduous caries. METHODS: An investigation on children's feeding
      methods, caries prevalence and dmft was made, using 260 cases which were provided
      with whole primary teeth. Chi-square test was used for statistical analysis on
      feeding methods and caries prevalence, and variance analysis was used on feeding
      methods and dmft. RESULTS: The results showed that the deciduous caries rate,
      mean dmft in breast feeding (BF) group were lower than those in mixed feeding
      (MF) group and artificial feeding (AF) group, there were significant differences
      between BF group and MF group,also between BF group and AF group. But there were
      no significant differences between MF group and AF group. CONCLUSION: It is
      concluded that proper breast feeding seems to be important for preventing
      deciduous caries.

PMID- 15514857
TI  - [The discrepancy between ICP and MCP caused by orthodontic treatment and its
      quantitative assessment to the effect of later orthodontic treatment.].
AB  - PURPOSE: To investigate the discrepancy between ICP and MCP caused by orthodontic
      treatment. to evaluate the treatment effect of the malocclusion with later
      orthodontic treatment. METHODS: Nineteen cases were selected and treated with
      preadjusted appliance and combination headgear appliance.Pre- and post- treatment
      celphalometric radiographs were analyzed. RESULTS: Discrepancy between ICP and
      MCP may be resulted from improper design and operation of orthodontists and poor
      cooperation of patients; By preadjusted appliance and combination headgear
      appliance,upper dental arch was moved distally; Molar relationship was changed
      into Class I by bodily movement; A harmonization between ICP and MCP was
      rehabilitated. CONCLUSIONS: The discrepancy between ICP and MCP should be minded;
      Preadjusted appliance and combination headgear appliance were effective in the
      correction of the discrepancy between ICP and MCP.

PMID- 15514858
TI  - [Electromyography study on complete bilateral cleft lip after reparation.].
AB  - PURPOSE: This study was undertaken to evaluate the motion effect of complete
      bilateral cleft lips objectively using electromyography. METHODS: 45 patients of
      complete bilateral cleft lips after operations several years which included 20
      patients repaired using orbicularis oris muscle restoring functional method and
      25 patients using straight line suture method were examined with electromyography
      (EMG) in prolabium, right and left lateral lips respectively. The most potential
      in every area of each patient at the maximal lip contraction position was
      measured and the values of two different method groups were subject to
      statistical analysis. RESULTS: The prolabium and lateral lips of both groups had
      no electric activity at posture position. At maximal contraction position, the
      mean potential of prolabium of orbicularis oris muscle restoring method group had
      no difference with the lateral lips. But the mean potential of prolabium of
      straight line suture method group was lower than that of the lateral lips
      significantly,also,it was lower than the potential of prolabium in the muscle
      functional reparation group. CONCLUSIONS: The reparation method of restoring
      orbicularis oris muscle to complete bilateral cleft lips was better than the
      straight line suture method in the motion effect. These findings suggest the
      superiority and necessity of functional muscle reparation for complete bilateral
      cleft lips.

PMID- 15514859
TI  - [Study of propofol target controlled infusion for blind tracheal intubation in
      anesthesia of oral and maxillofacial surgery.].
AB  - PURPOSE: To observe the clinical effects of propofol target controlled infusion
      for blind tracheal intubation in anesthesia of oral and maxillofacial surgery.
      METHODS: 80 cases with difficult airway of oral and maxillofacial surgery were
      divided into four groups. They were intubated by a new blind tracheal intubation
      technique.Before intubation,group 1,group 2,group 3 received fentanyl 4 microg/kg
      by intravenous infusion and propofol TCI 1.0 microg/ml,1.5 microg/ml,2.0
      microg/ml, respectively.Group 4 only received fentanyl 4 microg/kg. All patients
      underwent tracheal topical anesthesia.The effects of anesthesia in the four
      groups were observed and compared. RESULTS: Ramsay score in group 2 and group 3
      was obviously higher after administer propofol TCI (P<0.05).During intubation,
      group 2 and group 3 kept higher score than the other groups (P<0.05), MAP and HR
      changed smoothly and steadily in group 2 and group 3. But in group 1 and group 4,
      MAP and HR increased significantly (P<0.05). During intubation, RR decreased
      significantly in the four groups, but most serious in group 3 (P<0.05).There were
      no significant changes of SpO2, P(ET)CO2. After intubation, plasma PRL and plasma
      A II increased obviously in different degrees in the four groups,the increase in
      group 4 was higher than in group 3 (P<0.05). CONCLUSION: Propofol target
      controlled infusion is a good anesthesia method for blind tracheal intubation.It
      is safe and effective if target blood concentration controlled appropriately.

PMID- 15514860
TI  - [A cephalometric study of the craniofacial morphology in adult patients with
      unoperated cleft palate.].
AB  - PURPOSE: To evaluate the effects of cleft palate on the craniofacial morphology
      in adult patients with unoperated cleft palate by cephalometric analysis.
      METHODS: X-ray cephalometry was used for the study of craniofacial morphology
      carried out in 7 male and 8 female patients with unoperated cleft palate.
      Pointing measurements were done with the methods of Downs and Steiner. The data
      of the cephalometric measurements were compared with that of Guangxi native
      normal adults by t test. RESULTS: The unoperated cleft palate patient,s SNA,ANS
      Ptm(FH) and L1-MP were smaller or shorter than those of normal group while Po-NB
      was longer. There was significant difference between the two groups (P<0.05 or
      0.01). CONCLUSIONS: The deformities of adult patients with unoperated cleft
      palate were mainly considered to be that the anterior and posterior length of
      maxilla show hypoplastic while the vertical height of the maxilla the length of
      anterior cranial fossa and mandible was normal. But the retrusion of alveolar
      mandible led to chin protrusion.

PMID- 15514861
TI  - [Epidemic investigation on 3 to 6 years children's bruxism in Shanghai.].
AB  - PURPOSE: The present investigation analyzed the states of children bruxism in
      Shanghai, aiming for early diagnosis and early treatments. METHODS: The
      investigation was conducted through questionnaising 779 3-to-6-years-old
      children's parents. The data were processed using Chi square test. RESULTS:
      (1)The prevalence of children bruxism in Shanghai was about 38.4%; (2)151 males
      (40.6%) and 148 females (36.4%) had bruxism, which indicated no statistic
      difference in two genders(X2=1.47, P>0.05);(3)There seemed to exist hereditary
      difference between children with or without bruxism(X2=102.98, P<0.01).
      CONCLUSION: There is a high bruxism prevalence among children aged from 3 to 6
      years in Shanghai, which should be concerned about by the healthy care workers in
      order to make early diagnosis and treatment.

PMID- 15514862
TI  - [Microcosmic analysis of TCP/HA coating with micro-pores on titanium by IBAD
      method.].
AB  - PURPOSE: In order to improve the biocompatibility of dental implants, the
      physical structure and the chemical composites of tricalcium
      phosphate/hydroxyapatite(TCP/HA) coating on titanium were studied. METHODS:
      Coatings of TCP/HA and hydroxyapatite (HA) on titanium were formed by ion beam
      assisted deposition (IBAD) method. The scanning electron microscope (SEM) and
      atomic force microscope (AFM) were used to study the morphology of the coating
      surfaces. The chemical components and structure of the modified surfaces were
      characterized using energy dispersive X-ray analysis (EDX) and X-ray diffraction
      (XRD). RESULTS: The results showed that there were many micro-pores in the TCP/HA
      coating by SEM and AFM. The chemical components analysis showed that the Ca/P
      ratio of TCP/HA coating was lower than that of HA coating. The XRD showed that
      the TCP/HA coating was composed of TCP and HA. CONCLUSION: The results indicated
      that the TCP/HA coating with micro-pores was formed on titanium by IBAD method
      successfully. With higher binding strength between TCP/HA and titanium, this
      coating will be a potential coating material for dental implant, especially for
      the biological seal at the cervical level of the implant.

PMID- 15514863
TI  - [Guided reconstruction of soft tissue defects of the palate with n-HA/PA66
      plates: an experimental study in goats.].
AB  - PURPOSE: To evaluate the effect of n-HA/PA66 plate as a guided implant for the
      regeneration of the soft tissue defects in palatal region of goats. METHODS: 12
      goats were divided into experimental group and control group at random. 18.0 mm x
      14.0 mm soft tissue defect and 15.0 mm x 13.0 mm hard tissue defect were formed
      artificially in hard palate. n-HA/PA66 plates were implanted to the defect in the
      experimental group. The tissue regeneration in the defects was observed and the
      structure of regenerating tissue was analyzed by histology. RESULTS: The
      mucoperiosteal tissue in the experimental group regenerated along the n-HA/PA66
      plates and the mucoperiosteal defects were closed in 6 weeks. The soft and hard
      tissues were not closed up in control group in 6 weeks. CONCLUSION: n-HA/PA66
      plates can guide the regeneration of mucoperiosteal tissue to close the palatal
      defects.

PMID- 15514864
TI  - [Effect of fluorided etching fluid on the shear bond strength and the deposition
      on the surface of enamel.].
AB  - PURPOSE: The aim of this study was to find the best concentration of fluorided
      etching acid in the dental clinic which had both the best shear bond strength and
      the maximal anti-caries effect. METHODS: 84 extracted human premolars were
      divided into four groups of 21 teeth each. The enamel of each group was
      conditioned with 35% phosphoric acid containing 0%, 1.23%, 2%, 3% NaF. The shear
      bond strength was tested by bond strength machine and the enamel morphology was
      observed by scanning electron microscopy at once, 1 week, 4 weeks, 12 weeks, 24
      weeks after etching. The shear bond strength was statistically analyzed by
      SPSS10.0 software. RESULTS: The shear bond strength of the group whose acid
      containing 3% NaF was less than the others significantly (P<0.05); and there was
      no significant difference among the other groups (P>0.05). The amount of the
      deposition on the surface of enamel after etching was increased with the time
      after etching and the concentration of NaF increasing. CONCLUSIONS: 2% NaF added
      to 35% phosphoric acid has both the best bond strength and the best effect of
      preventing enamel from caries.

PMID- 15514865
TI  - [Analysis of p53 gene mutation in salivary adenoid cystic carcinoma.].
AB  - PURPOSE: The purpose of this study was to investigate the occurrence of p53 gene
      mutation in salivary adenoid cystic carcinoma, the correlation between the gene
      and prognostic significance. METHODS: A series of salivary adenoid cystic
      carcinoma were studied by polymerase chain reaction and single strand
      conformation polymorphism (PCR-SSCP) analysis to detect p53 mutation,
      respectively. RESULTS: The result showed that p53 gene mutations in exon 5-8 were
      detected in 65.8% (25/38) of the salivary adenoid cystic carcinoma. The p53 gene
      mutation was related to tumor distant metastasis and tumor recurrence (P<0.05)
      but not related to pathological types, clinical stages (P>0.05).There was a
      significant correlation between p53 gene mutation and postoperative survival .
      CONCLUSION: It is suggested that p53 gene mutations were very common in salivary
      adenoid cystic carcinoma, and might be useful in screening progress and
      evaluating prognosis of patients.

PMID- 15514866
TI  - [Relationship between the vertical loop structure and the mechanical
      properties.].
AB  - PURPOSE: The relationship between vertical loop structure and its mechanical
      properties was investigated in order to provide reference data for more proper
      use of vertical loop. METHODS: According to the acting manner in use, finite
      elements model of vertical loop was established and the finite elements software
      ANSYS was used to simulate the mechanical characteristics of the loops. The
      simulated data were summarized at the end. RESULTS: The force and moment
      decreased with the increase of arm length, height and arc radius of the loop. The
      ratios of force to moment (M/F) decreased with the increase of arm length, but
      increased with the increase of height and arm radius. When the interval between
      the vertical arms enlarged, the force and moment rose and the M/F did not vary
      significantly. CONCLUSION: To satisfy the requirement of individual patient, the
      structure of loop can be adjusted properly to output mediate force, moment and
      M/F value.

PMID- 15514867
TI  - [Effect of coronal preflaring on the instrumentation of curved premolar canals.].
AB  - PURPOSE: To study the effect of coronal preflaring on the instrumentation of
      curved premolar canals. METHODS: Sixty extracted premolars, with the degree of
      root canal curvature from fifteen to thirty-five, were divided into fifteen
      sections in curvature sequence. After that, four canals of each section were
      randomly distributed to four different instrumentational groups. Two groups were
      coronally preflared with Gates Glidden drills first. Then they were instrumented
      by stainless steel or nickel titanium K-files from 15# to 40# with sequential
      preparation to working length. The other two groups were prepared directly with
      the above-mentioned two instruments. The standard digital radiographs were taken
      to record the position of the tip of the different sizes of instruments. At last,
      the curvature degrees were measured and the apical transportation indexes (ATI)
      were determined under stereomicroscope. t test or rank test for paired data was
      used for statistical analysis. RESULTS: The curvature degree before and after
      instrumentation for each group was significantly different (P<0.01). The larger
      the files were, the greater the ATI became. The cases of root perforations in the
      stainless steel K-files group became fewer after coronal preflaring. The ATI of
      30# for stainless steel K-files were much less after coronal preflaring, and were
      not significantly different with the ATI for nickel titanium instruments
      (P>0.05). CONCLUSION: The effect of nickel titanium instruments was superior to
      that of stainless steel instruments by comparing the change of curvature degree
      and the ATI of preparing curved premolars root canals. Coronal preflaring should
      be performed first when the root canals were instrumented by stainless steel K
      files or nickel titanium instruments with sequential preparation technique.

PMID- 15514868
TI  - [Effect of irradiation power on the mechanical properties of laser-welded
      titanium joints.].
AB  - PURPOSE: To make an clinical implication for the use of laser welding pure
      titanium,this study investigate the effect of irradiation power on the mechanical
      properties of laser-welded joints. METHODS: The pure titanium tensile test and
      three-point bending test rods were laser-welded with different irradiation power.
      Then the tensile rods were tested for the ultimate tensile strength (UTS), and
      the bending rods for the ultimate bending strength (UBS). The tensile fracture
      surface was examined by scanning electron microscopy (SEM). Metallurgical
      analysis was also performed on polished longitudinal sectioned samples. RESULTS:
      A small portion of the central area in group 1.4 kW was not joined. ANOVA showed
      no significant difference of OTS and VBS between group 1.6 kW and group 1.8 kW at
      the 0.05 level. SEM examination and metallurgical analysis showed that there were
      defects such as pores and cracks in the welding zone; and as the irradiation
      power increased, there were more pores and cracks. CONCLUSION: The increase in
      laser irradiation power cannot increase melting depth significantly.

PMID- 15514869
TI  - [An experimental study on laser-welded dissimilar alloys in dentistry.].
AB  - PURPOSE: This study evaluated the mechanical properties and microstructure of the
      joints of laser-welded dissimilar alloys usually used in clinical nowadays.
      METHODS: The dissimilar alloys for Co-Cr alloy,Ni-Cr alloy and pure titanium were
      laser-welded. The joints were tested for the ultimate tensile strength (UTS) and
      the ultimate bending strength (UBS). The tensile fracture surfaces were examined
      by scanning electron microscopy (SEM). Metallurgical analysis was also performed
      on polished longitudinal sectioned samples. RESULTS: Laser-welded dissimilar
      alloys between Co-Cr and Ni-Cr alloy can yield satisfactory mechanical
      properties, and there was no significant difference of UTS and UBS between Co-Cr
      welding wire group and Ni-Cr welding wire group (P>0.05). The laser-welded joints
      for dissimilar metal of pure titanium and Co-Cr,pure titanium and Ni-Cr, showed
      more brittle characteristics and severe defects (pores and cracks). CONCLUSIONS:
      With Co-Cr or Ni-Cr welding wire, the laser-welded dissimilar alloys of Co-Cr
      alloy and Ni-Cr alloy can yield satisfactory joints. But pure titanium and Co-Cr
      alloy, pure titanium and Ni-Cr alloy cannot be directly melted together.

PMID- 15514870
TI  - [Effect of laser irradiation power on the mechanical properties of Co-Cr and Ni
      Cr laser-welded joints.].
AB  - PURPOSE: To investigate the effect of different irradiation power on the
      mechanical properties of laser-welded joints. METHODS: The standard tensile test
      and three-point bending test rods made from Co-Cr and Ni-Cr alloy were laser
      welded with different irradiation powers. Then the tensile rods were tested for
      the ultimate tensile strength (UTS), and the bending rods for the ultimate
      bending strength (UBS). The tensile fracture surface was examined by scanning
      electron microscopy (SEM). Metallurgical analysis and microhardness test were
      also performed on polished longitudinal sectioned samples. RESULTS: For Co-Cr
      alloy, greater irradiation power resulted in greater UTS, minor UBS. For Ni-Cr
      alloy, there was no significant difference of UTS and UBS between the four
      groups. SEM and metallurgical examination showed that the welded zone exhibited
      more gas pores and cracks as the irradiation power increased. Microhardness test
      showed that hardness increased toward the center of the welded zone and as the
      irradiation power increased, the range of hardness increased was expanded.
      CONCLUSION: The optimal laser irradiation power was the key to achieved superior
      mechanical properties joints.

PMID- 15514871
TI  - [Expression of cellular adhesion molecules and HLA-DR antigen on vascular
      endothelial cells in hemangiomas.].
AB  - PURPOSE: To investigate the expression and function of the adhesion molecules
      ICAM-3, CD34 and HLA-DR antigen on endothelial cells of hemangiomas in different
      stages. METHODS: SABC immunohistochemical technique was used to examine the
      expression of ICAM-3, CD34 and HLA-DR on vascular endothelial cells. Seventy-six
      specimens including 28 proliferating hemangiomas, 22 involuting hemangiomas, 18
      vascular deformity and 8 normal skin tissue were obtained from infants and
      children for the experiment. RESULTS: The results showed: (1) both ICAM-3 and
      CD34 had high expression in proliferating hemangiomas, but poor or even no
      expression in involuting hemangiomas. There was a significant difference
      (P<0.001) between the two phases. Both ICAM-3 and CD34 had almost no expression
      in vascular deformity and normal skin tissue, significantly different from
      hemangiomas (P<0.001).(2) HLA-DR expression was closely related to the high
      differentiation phase of vascular epithelial cells. In the proliferating phase,
      HLA-DR didn't express, while it expressed highly as endothelial cells were in
      well-matured involuting phase. These differences were significant (P<0.001).
      CONCLUSION: ICAM-3 and CD34 might play a role in the early stage of angiogenesis
      and take part in the pathological genesis and regression process of hemangiomas
      by regulating endothelial cells adhesion; HLA-DR might be related either to
      acquisition of a mature phenotype or to an activated state of the endothelial
      cells.

PMID- 15514872
TI  - [A review of correlation, regression and multiple factors analysis methods.].
AB  - In clinical research, the relationships between two factors or among multiple
      factors are frequently explored. Dependence and covariation are two kinds of
      relationships between two factors. Regression and correlation analysis are the
      appropriate methods in measuring and evaluating those factors. Multiple analysis
      methods are widely used in the studies of risk factors among diseases, data
      analyses of diagnostic tests, effects evaluation of a prevention and treatment,
      analyses of prognosis, etc. Multiple analysis methods could interpret the
      influences of each factor more specifically than single factor analysis, and
      provide more possibilities to improve the quality of a research. In this review,
      the fundamental principle and utilities on clinical research of several
      statistical methods are introduced in this paper, such as linear correlation,
      linear regression, rank regression, rank correlation, multiple linear regression
      and logistic regression. It intends to help the clinicians and researchers to
      select the appropriate statistical methods to collect and analyze the data.

PMID- 15514873
TI  - [The role of the mouthguard in preventing sports-related oral-facial and dental
      traumas.].
AB  - Sports play a significant role in all nations worldwide. More and more people
      involve in sports so that the incidence of the oral-facial and dental traumas
      with accidents ascends. The treatment cost is considerable, and the sporters'
      lives will be influenced by these traumas. This paper examines the status and the
      reasons of the oral-facial and dental traumas. It reviews not only the principle
      and the types of the mouthguard but also the evidence of the mouthguard in
      preventing sports-related traumas. Prevention is thought to be the key element in
      minimizing traumas that occur in sports, the using of mouthguard is considered
      essential.

PMID- 15514874
TI  - [Clinical observation of the height of the alveolar after bone grafting in cleft
      alveolar repair in various ages.].
AB  - PURPOSE: To evaluate the changes of transplanted bones after cancellous iliac
      bone grafting in cleft alveolar repair in various ages. METHODS: The patients
      were divided into A and B groups according to their canine eruption. The changes
      of alveolar height in grafting regions were examined by clinical follow up and
      radiographs after the cancellous iliac bone grafting in cleft alveolar repair.
      RESULTS: The bone grafting before the eruption of canines was more effective than
      that after eruption. The orthodontics after operation can increase the alveolar
      height. CONCLUSION: The alveolar height after the bone grafting in cleft alveolar
      repair increased with the eruption of canines.

PMID- 15514875
TI  - [Treatment effects of the maxillary protraction in correction of maxillary
      deficiency: a comparative study between RPE group and no RPE group.].
AB  - PURPOSE: To compare the clinical effects of rapid palatal expansions combined
      with maxillary protractions to that of maxillary protractions of the maxillary
      deficiency alone. METHODS: Twenty patients aging from 9 to 11 years were divided
      into two groups , each group had 10 patients. All patients were diagnosed as
      having deficient maxillas with anterior crossbite. Group A were treated with
      rapid palatal expansion before maxillary protraction.Group B were treated with
      maxillary protraction alone. Lateral cephalometric films were taken at the
      beginning and the end of the treatment, and analyzed with McNamara analysis (Co
      A,Co-Gn,ANS-Me) and traditional analysis. RESULTS: (1) After maxillary
      protraction,the maxilla and upper dentitions were protracted in both groups,the
      anterior crossbite had been corrected and obvious profile changes can be
      observed. (2) The mandible moved backward and downward in the RPE group and more
      obvious profile changes can be achieved compared with no RPE group. CONCLUSION:
      (1) It's an effective method to manage the maxillary deficiency with maxillary
      protraction in the mixed dentition. (2) Applying maxillary protraction combined
      with RPE is more adaptable to low angle cases.

PMID- 15514876
TI  - [Treatment of delayed complex malhealed jaw fractures in 32 patients.].
AB  - PURPOSE: Three methods were used to manage delayed complex malhealed jaw
      fractures in 32 patients. The indication for each method and final result was
      evaluated. METHODS: Three methods included conservative therapy, internal
      fixation and orthognathic surgery. In conservative therapy, intermaxillary
      fixation was obtained with dental arch splints. In internal fixation, ordinary
      operation was performed including open exposure of the fractured segments,
      anatomical reposition and rigid fixation with steel wire or titanium miniplates.
      In some patients, orthognathic surgery was carried out with intermaxillary
      ligation for 2 to 3 weeks postoperatively. RESULTS: All the wounds healed
      primarily without significant complications. The postoperative occlusion and
      appearance were satisfactory or fair. CONCLUSIONS: The selection of treatment
      methods should be based on the location, time, severity of the fracture and the
      patients' age, in order to achieve maximal recovery of mastication and
      appearance.

PMID- 15514877
TI  - [Dental implants in patients with Type 2 diabetes mellitus: a clinical study.].
AB  - PURPOSE: The oral rehabilitation by dental implants in patients with diabetes
      remains a controversial issue.The aim of this study was to investigate the
      clinical results of implantation in patients with Type 2 diabetes mellitus.
      METHODS: This study group consisted of 21 patients with Type 2 diabetes mellitus
      who received 52 implants. RESULTS: There were 5 failures.The success rate was
      90.4% with a follow up period of 12 to 37 months. CONCLUSIONS: The clinical
      outcome of dental implants in selected group of patients with well-controlled
      type 2 diabetes mellitus is satisfying and encouraging.Further investigations and
      clinical trials over a longer period of time are needed to determine the long
      term survival of implants in diverse of patients with diabetes mellitus.

PMID- 15514878
TI  - [An evaluation of the speech therapy methods for patients after pharyngoplasty.].
AB  - PURPOSE: Speech therapy was carried out for patients with speech disorders after
      pharyngoplasty, and the comparison of speech articulation before and after
      treatment, was done to evaluate the new method. METHODS: 82 patients with the
      varying age from 4 to 31 years were included in the current study. The patients'
      speeches including syllables, word, phrase and sentence were compared before and
      after treatment according to Chinese Speech Intelligibility Testing Form. The
      systematic speech training was carried out according to the compensatory
      articulation characteristics. The steps were as follows. Firstly, the function of
      velopharyngeal closure should be strengthened. Secondly, the patients were
      trained with an average duration of 3.83 months (range from 1.5-12 months)
      according to the following three sequences: One was from phoneme, syllables,
      phrase, sentence to short paragraph or dialogue, another was from anterior to
      posterior according to the speech position, and the other was from easy to
      difficult according to the articulation method, such as from aspirated syllables
      to non-aspirated syllables, from plosive, fricative to affricative. RESULTS:
      There were 71 patients with compensatory articulation characteristic of
      velopharyngeal incompetence, the speech articulation of patients with glottis
      plosive increased from preoperative 46.27% to postoperative 97.16% (P<0.001). The
      speech articulation of patients with pharynx fricative increased from
      preoperative 57.19% to postoperative 97.72% (P<0.001). There were 11 patients
      with compensatory articulation characteristic of velopharyngeal adequacy, and the
      speech articulation of 11 patients with palatalized and lateral misarticulation
      increased from preoperative 71.10% to postoperative 98.55% (P<0.001).
      CONCLUSIONS: The training of velopharyngeal closure should be emphasized on the
      patients with compensatory articulation resulting from velopharyngeal
      incompetence after pharyngoplasty, then the correct speech position and method
      was established. While to the patients with compensatory articulation without
      velopharyngeal incompetence after pharyngoplasty, the correct speech position and
      method could be directly established.

PMID- 15514879
TI  - [Comparison of the apical sealability of two canal obturation methods.].
AB  - PURPOSE: To compare the apical sealability of canal obturation with lateral
      condensation (LC) and combined LC with vertical condensation (hybrid
      condensation, HC). METHODS: 79 single canal extracted anterior teeth were
      instrumented with step-back technique and then randomly divided into three group.
      Group A was obturated only with LC; group B was obturated with HC. group C was as
      control group. All teeth were dyed in 1% india ink for 72 hours, then split into
      two parts longitudinally. The linear length of dye was measured as the result of
      microleakage. RESULTS: The linear length of microleakage between group A and
      group B had significant difference (P<0.01). The microleakage of HC was lower
      than LC. CONCLUSION: The vertical condensation to gutta-percha at crown third
      after canal obturation with LC could reduce the apical microleakage.

PMID- 15514880
TI  - [A comparison of the effect between Vitapex paste and antibiotic paste in
      apexification.].
AB  - PURPOSE: To study the effects of two root canal filling material in the
      apexification. METHODS: 172 juvenile permanent teeth,including 62 teeth with
      pulpitis, 32 teeth with necrotic pulp and 78 teeth with periapical periodontitis,
      were divided into two groups.The root canal was filled with Vitapex paste and
      antibiotic paste.Every patient was examined once three months.The treatment
      lasted 6-30 months.The outcome of treatment was investigated for three years
      following treatment. RESULTS: The effective rate in the group of Vitapex paste
      and antibiotic paste group were 86.0% and 91.9% (P>0.05).In periapical
      periodontitis group,the effective rate of antibiotic paste group was
      significantly higher than the other (P<0.05). CONCLUSION: Both Vitapex paste and
      antibiotics paste were good filling materials in apexification. Antibiotic paste
      was better than the other in periapical periodontitis group.

PMID- 15514881
TI  - [Analysis of conservative therapies for posterior teeth with longitudinal
      fractures.].
AB  - PURPOSE: To explore the ideal method for conservative therapies of posterior
      teeth with longitudinal fracture. METHODS: The records of 297 cases undergoing
      conservative treatment of posterior teeth with longitudinal fracture were
      analyzed regarding to the position, etiology and the time of treatment from
      fracture and the causes of failure. RESULTS: 258 cases were conserved effectively
      and 39 cases were extracted due to failure.16 cases had failure 1 week after
      treatment. All the patients were followed up for 2 to 10 years, and the rate of
      success was 86.87%. CONCLUSION: With fixed early and appropriate treatment, the
      teeth can be conserved effectively and exert good masticatory function .

PMID- 15514882
TI  - [Location and dilation of the second mesiobuccal canals in maxillary molars.].
AB  - PURPOSE: To Locate and dilate the second mesiobuccal canals(MB2) in clinical
      treatment and in extracted molars in maxillary molars. METHODS: 11 extracted
      maxillary molars were studied. MB2s were searched and dilate the canals were
      filled with gutta-percha and then x ray film were taken. 146 maxillary molars
      included 94 maxillary first molars and 52 maxillary second molars were attempted
      to locate and dilate for MB2.Then root canal treatment was carried out in molars
      and x ray film were taken. RESULTS: MB2 canal can be located in 60% and dilate
      50% of 10 extracted maxillary first molars. MB2 canal can be located in 44.68%
      and dilated in 29.78% of maxillary first molars. MB2 canal can be in located in
      11.53% and dilated in 7.69% of maxillary second molars. CONCLUSION: The
      occurrence of MB2 is high in maxillary first molars. Although there are many
      difficulties in location and dilate of MB2, attempt should be conducted to
      explore in order to increase rate incidence of root canal therapy.

PMID- 15514883
TI  - [Root canal therapy opportunity in replanted teeth due to injury.].
AB  - PURPOSE: To investigate the opportunity of different root canal therapies in
      replantation of tooth due to injury. METHODS: 49 cases with teeth luxation were
      randomly divided into three groups. In group A, the pulp was removed before
      replanted, and calcium hydroxide was filled in root canals and condensated
      routinely after half a year. In group B, the pulp was removed one week after
      being replanted. In group C, the pulp was removed until pulp disease. RESULTS:
      The effect of group A(81.25%) and B (94.44%) was better than group C (53.33%),
      P<0.05. And the effect of group A and B was similar. CONCLUSION: It's an ideal
      method to replant luxated tooth within 3 hours with removal of pulp tissue, root
      canal filling with calcium hydroxide one week after replantation of tooth and
      condensated routine root canal therapy after half a year.

PMID- 15514884
TI  - [Comparison of the clinical effects of three root canal treatments.].
AB  - PURPOSE: To compare the clinical effects of three root canal treatments. METHODS:
      The patients were randomly divided into A,B,C groups. Group A: profile
      preparation of the root canal, then the root canal was filled with maillefer
      thermafil. Group B: profile preparation of the root canal, iodoform cataplasm and
      gutta percha point was used to fill root canal. Group C: preparation of the root
      canal with stainless steel hand-operated root canal magnified instrument,
      iodoform cataplasm and gutta percha point was used to fill the root canal.
      RESULTS: Through X ray and clinical evaluation, the root canal therapy result in
      group A was superior to group B, group B was superior to group C. CONCLUSION: The
      work efficiency of preparative instrument of profile flexible nickel-titanium
      root canal is high. The successful rate of maillefer thermafil for results root
      canal therapy is superior to the other methods. Root canal preparation by profile
      can get satisfying effects.

PMID- 15514885
TI  - [Malignant ameloblastoma of the jaw: an analysis of 10 consecutive cases.].
AB  - PURPOSE: To investigate the clinical and radiographic manifestations of malignant
      ameloblastoma of the jaw and methods for treatment. METHODS: 10 consecutive cases
      of malignant ameloblastoma were treated in the Department of Oral and
      Maxillofacial Surgery, Ninth People's Hospital,Shanghai Second Medical University
      between 1991 and 2003. All the cases were proved to be malignant ameloblastoma by
      surgical pathology and followed up for 1 to 8 years. This paper reviewed the
      clinical manifestation, diagnosis and treatment of these 10 cases. RESULTS: Among
      the 10 cases of malignant ameloblastoma, 5 were female, 5 were male ,aged from 22
      to 60 years. 4 cases were located in the maxilla, and 6 cases in the mandible.All
      the patients underwent partial mandibulectomy or maxillectomy combined with
      modified radical neck dissection or supraomohyoid dissection with flap repair at
      the same time. The follow up outcomes were satisfactory both in appearance and
      function without recurrence. CONCLUSION: Malignant ameloblastoma is a kind of low
      degree malignant tumors. Diagnosis is made by pathology. Operation is the only
      radical method of therapy.

PMID- 15514886
TI  - [Clinical study of bioglass for repairing alveolar cleft.].
AB  - PURPOSE: To analyse the results of using Bioglass to repair alveolar cleft.
      METHODS: Thirty-nine cases with alveolar cleft were divided into two groups. In
      group A, autogenous iliac cancellous bone were transplanted into the cleft to
      repair alveolar defect in 25 cases, while artificial bone-Bioglass was used in
      group B of 14 cases. The results of two groups were compared with a follow up of
      12 months. RESULTS: New bone formation was perfect in grafted area and canines
      can emerge from the bone grafted areas observed from the X-ray films both in
      group A and group B. Statistical analysis showed no significant difference
      between group A and group B in the clinical success rate of alveolar cleft
      repair. However, there was significant difference between complete alveolar cleft
      and incomplete alveolar cleft in group A and group B. CONCLUSION: Bioglass can
      result in new bone formation and eruption of canines from the bone grafted areas.
      The application of Bioglass in repairing of alveolar cleft provides a new therapy
      for alveolar cleft patients.

PMID- 15514887
TI  - [Effect of static magnetic field on proliferation and cell cycle of osteoblast
      cell.].
AB  - Rat calvarias osteoblasts were cultured and put in the static magnetic field of 0
      Gs, 400 Gs, 620 Gs, 830 Gs and 1080 Gs for 24 h, 48 h and 72 h, respectively. MTT
      method was used for detecting osteoblast proliferation and flow cytometry for
      detecting cell cycle. When the magnetic exposure time extended to 48 h or 72 h,
      the corresponding OD value of osteoblast with magnetic treatment of 400 Gs or 620
      Gs increased obviously with significant difference as compared with 0 Gs group
      (P<0.05), but such proliferative effect was not shown in the 1080 Gs group
      (P>0.05). After magnetic exposure with intensity of 620 Gs, G0/G1 phase
      percentage decreased, but S phase and G2/M phase percentage was significantly
      higher as compared with control. Proliferation index (PI) increased as well and
      there was significant difference in contrast to control (P<0.05). Within a
      certain range of magnetic intensity, magnetic field enhances cell growth in a
      dose-dependent pattern. And static magnetic field can activate static G1 phase
      into S phase, increase DNA synthesis, and accelerate cell proliferation.

PMID- 15514888
TI  - [Successful tracheal intubation in a child with facial multi-clefts and difficult
      airway: case report.].
AB  - A male patient, aged 7 years, was intended to undergo plastic surgery under
      general anesthesia with tracheal intubation for his severe facial abnormities as
      a result of 5, 6, 7 combined facial clefts. Because of his severe facial
      abnormities and preoperative undetected bilateral antiadoncus, during the period
      of induction, dyspnoea and dysventilation took place, which were relieved by
      inserting a medium-sized oropharyngeal airway with difficulty; during
      euthyphoirally exploring his endolarynx with direct laryngoscope, laryngospasm
      occurred, which was relieved through inserting airway and pressurizing
      ventilation; repetitively attempted to blindly insert tracheal intubation through
      nostril, but failed. Finally, his intubation was achieved by blindly intubating
      through oral cavity under the assistance of direct laryngoscope.

PMID- 15514890
TI  - Chronic and recurrent otitis media: a genome scan for susceptibility loci.
AB  - Otitis media (OM) is the most common childhood disease. Almost all children
      experience at least one episode, but morbidity is greatest in children who
      experience chronic/recurrent OM (COME/ROM). There is mounting evidence that
      COME/ROM clusters in families and exhibits substantial heritability. Subjects who
      had tympanostomy tube surgery for COME/ROM (probands) and their families were
      recruited for the present study, and an ear examination was performed, without
      knowledge of the subject's history, to determine presence of OM sequelae. In
      addition, tympanometric testing was performed at three frequencies (226, 630 or
      710, and 1,400 Hz) to detect abnormal middle-ear mechanics, and hearing was
      screened at 20 dB for the speech frequencies. Of these families, 121 had at least
      two individuals who had received the diagnosis of COME/ROM (364 affected and
      genotyped individuals), of whom 238 affected and informative relative pairs were
      used for analyses. Single-point nonparametric linkage analysis provided evidence
      of linkage of COME/ROM to chromosome 10q at marker D10S212 (LOD 3.78; P=3.0 x 10(
      5)) and to chromosome 19q at marker D19S254 (LOD 2.61; P=5.3 x 10(-4)). Analyses
      conditional on support for linkage at chromosomes 10q and 19q resulted in a
      significant increase in LOD score support on chromosome 3p (between markers
      D3S4545 and D3S1259). These results suggest that risk of COME/ROM is determined
      by interactions between genes that reside in several candidate regions of the
      genome and are probably modulated by other environmental risk factors.

PMID- 15514889
TI  - Comparison of microsatellites versus single-nucleotide polymorphisms in a genome
      linkage screen for prostate cancer-susceptibility Loci.
AB  - Prostate cancer is one of the most common cancers among men and has long been
      recognized to occur in familial clusters. Brothers and sons of affected men have
      a 2-3-fold increased risk of developing prostate cancer. However, identification
      of genetic susceptibility loci for prostate cancer has been extremely difficult.
      Although the suggestion of linkage has been reported for many chromosomes, the
      most promising regions have been difficult to replicate. In this study, we
      compare genome linkage scans using microsatellites with those using single
      nucleotide polymorphisms (SNPs), performed in 467 men with prostate cancer from
      167 families. For the microsatellites, the ABI Prism Linkage Mapping Set version
      2, with 402 microsatellite markers, was used, and, for the SNPs, the Early Access
      Affymetrix Mapping 10K array was used. Our results show that the presence of
      linkage disequilibrium (LD) among SNPs can lead to inflated LOD scores, and this
      seems to be an artifact due to the assumption of linkage equilibrium that is
      required by the current genetic-linkage software. After excluding SNPs with high
      LD, we found a number of new LOD-score peaks with values of at least 2.0 that
      were not found by the microsatellite markers: chromosome 8, with a maximum model
      free LOD score of 2.2; chromosome 2, with a LOD score of 2.1; chromosome 6, with
      a LOD score of 4.2; and chromosome 12, with a LOD score of 3.9. The LOD scores
      for chromosomes 6 and 12 are difficult to interpret, because they occurred only
      at the extreme ends of the chromosomes. The greatest gain provided by the SNP
      markers was a large increase in the linkage information content, with an average
      information content of 61% for the SNPs, versus an average of 41% for the
      microsatellite markers. The strengths and weaknesses of microsatellite versus SNP
      markers are illustrated by the results of our genome linkage scans.

PMID- 15514891
TI  - Polymorphisms in the sclerosteosis/van Buchem disease gene (SOST) region are
      associated with bone-mineral density in elderly whites.
AB  - Osteoporosis has a strong genetic component, but the genes involved are poorly
      defined. We studied whether the sclerosteosis/van Buchem disease gene (SOST) is
      an osteoporosis-risk gene by examining its association with bone-mineral density
      (BMD). Mutations in SOST result in sclerosteosis, and alterations in the SOST
      gene expression may be causal in the closely related van Buchem disease. We used
      a set of eight polymorphisms from the SOST gene region to genotype 1,939 elderly
      men and women from a large population-based prospective-cohort study of Dutch
      whites. A 3-bp insertion (f=0.38) in the presumed SOST promoter region (SRP3) was
      associated with decreased BMD in women at the femoral neck (FN) (P=.05) and
      lumbar spine (LS) (P=.01), with evidence of an allele-dose effect in the oldest
      age group (P=.006). Similarly, a G variant (f=0.40) in the van Buchem deletion
      region (SRP9) was associated with increased BMD in men at the FN (P=.007) and LS
      (P=.02). In both cases, differences between extreme genotypes reached 0.2 SD. We
      observed no genotype effects on fracture risk, for the 234 osteoporotic fractures
      validated during 8.2 years of follow-up and for the 146 vertebral prevalent
      fractures analyzed. We did not find association between any of several frequent
      haplotypes across the SOST gene region and BMD. We did find evidence of additive
      effects of SRP3 with the COLIA1 Sp1 polymorphism but not with haplotypes of 3'
      polymorphisms in the vitamin-D receptor gene. The SOST-COLIA1 additive effect
      increased with age and reached 0.5 SD difference in BMD at LS in the oldest age
      group (P=.02). The molecular mechanism whereby these moderate SOST genotype
      effects are mediated remains to be elucidated, but it is likely to involve
      differences in regulation of SOST gene expression.

PMID- 15514892
TI  - A 77-kilobase region of chromosome 6p22.2 is associated with dyslexia in families
      from the United Kingdom and from the United States.
AB  - Several quantitative trait loci (QTLs) that influence developmental dyslexia
      (reading disability [RD]) have been mapped to chromosome regions by linkage
      analysis. The most consistently replicated area of linkage is on chromosome 6p23
      21.3. We used association analysis in 223 siblings from the United Kingdom to
      identify an underlying QTL on 6p22.2. Our association study implicates a 77-kb
      region spanning the gene TTRAP and the first four exons of the neighboring
      uncharacterized gene KIAA0319. The region of association is also directly
      upstream of a third gene, THEM2. We found evidence of these associations in a
      second sample of siblings from the United Kingdom, as well as in an independent
      sample of twin-based sibships from Colorado. One main RD risk haplotype that has
      a frequency of approximately 12% was found in both the U.K. and U.S. samples. The
      haplotype is not distinguished by any protein-coding polymorphisms, and,
      therefore, the functional variation may relate to gene expression. The QTL
      influences a broad range of reading-related cognitive abilities but has no
      significant impact on general cognitive performance in these samples. In
      addition, the QTL effect may be largely limited to the severe range of reading
      disability.

PMID- 15514893
TI  - Genetic inheritance of gene expression in human cell lines.
AB  - Combining genetic inheritance information, for both molecular profiles and
      complex traits, is a promising strategy not only for detecting quantitative trait
      loci (QTLs) for complex traits but for understanding which genes, pathways, and
      biological processes are also under the influence of a given QTL. As a primary
      step in determining the feasibility of such an approach in humans, we present the
      largest survey to date, to our knowledge, of the heritability of gene-expression
      traits in segregating human populations. In particular, we measured expression
      for 23,499 genes in lymphoblastoid cell lines for members of 15 Centre d'Etude du
      Polymorphisme Humain (CEPH) families. Of the total set of genes, 2,340 were found
      to be expressed, of which 31% had significant heritability when a false-discovery
      rate of 0.05 was used. QTLs were detected for 33 genes on the basis of at least
      one P value <.000005. Of these, 13 genes possessed a QTL within 5 Mb of their
      physical location. Hierarchical clustering was performed on the basis of both
      Pearson correlation of gene expression and genetic correlation. Both reflected
      biologically relevant activity taking place in the lymphoblastoid cell lines,
      with greater coherency represented in Kyoto Encyclopedia of Genes and Genomes
      database (KEGG) pathways than in Gene Ontology database pathways. However, more
      pathway coherence was observed in KEGG pathways when clustering was based on
      genetic correlation than when clustering was based on Pearson correlation. As
      more expression data in segregating populations are generated, viewing clusters
      or networks based on genetic correlation measures and shared QTLs will offer
      potentially novel insights into the relationship among genes that may underlie
      complex traits.

PMID- 15514894
TI  - [A study and follow-up of ten cases of benign enlargement of the subarachnoid
      spaces].
AB  - AIM: To present 10 cases with 'benign enlargement of the subarachnoid spaces' and
      its clinical and image evolution. PATIENTS AND METHODS: We study 10 patients, 7
      boys and 3 girls, because of macrocephaly. It was made a clinic and image follow
      up from the first year of age to their cure. In the series, there are two
      monozygotic twins. RESULTS: The patients had normal head circumference centile at
      birth, and it was 90 or higher at the age of 5 to 12 months, to keep stabilized,
      without decreasing, during the time of the study despite disappearing enlargement
      of the subarachnoid spaces. CT and especially magnetic resonance studies, showed
      the largest subarachnoid spaces and lateral ventricles between 5 and 12 months of
      age, and then, a slowly decrease to disappear in a period that was variable among
      the patients. A moderate enlargement was still found after 5 years of age in some
      cases. The clinic and image follow-up showed a parallel evolution since birth to
      5 years in the pair of homozygous twins. Both showed possible reflux of the
      cerebrospinal fluid from the subarachnoid spaces to the cerebral ventricles,
      appearing cyst of the septum pellucidum, possibly due to the increase of the
      intraventricular pressure. The cyst did not disappear and kept the same size
      despite disappearing the enlargement of the subdural spaces and the normalization
      of the ventricular size. Psychomotor evolution has been normal, although most of
      patients show discrete hypotonus and motor coordination problems, attention
      deficit and/or hyperactivity. CONCLUSION: Benign enlargement of the subarachnoid
      spaces has a spontaneous solution, but it can carried out in some cases more
      slowly than it is though. The disease seems hereditary and the most probable
      etiology is the difficulty in absorption of the cerebrospinal fluid during the
      first year of life or still longer. The picture, however, always has a
      spontaneous solution.

PMID- 15514895
TI  - [Oropharyngeal dysphagia in patients with multiple sclerosis].
AB  - AIMS: The aim of this study is to evaluate the prevalence of the clinical and
      videofluoroscopic (VDF) symptoms of oropharyngeal dysphagia in patients with
      multiple sclerosis, and to describe its therapeutic management. PATIENTS AND
      METHODS: We studied 23 patients suffering from multiple sclerosis to evaluate the
      characteristics of the disease, the VDF exploration of swallowing and therapeutic
      strategies. The VDF exploration enables us to define the VDF symptoms that assess
      the safety and efficiency of swallowing for the oral and pharyngeal phases. The
      therapeutic strategies include: changes in the characteristics of the diet,
      changes of posture and active manoeuvres. RESULTS: The patients studied presented
      a mean EDSS score 7.4 (4-9). There were alterations in swallowing efficiency
      and/or safety in more than 80% of the patients. In 52% there was some change in
      the swallowing safety. 40% of them were silent aspirators. All these patients
      were fed orally without any complications, in 78% the volume of the bolus has
      been modified and changes have taken place in the consistency (thickening for
      liquids); in 43%, moreover, postural strategies were employed and active
      manoeuvres (supraglottic swallow) were introduced in 13% in order to improve
      swallowing safety. CONCLUSIONS: There is a high prevalence of clinical and VDF
      symptoms of oropharyngeal dysphagia in patients with advanced multiple sclerosis.
      VDF enables us to diagnose the pathophysiological mechanism of aspiration and the
      existence of silent aspirators, and helps us to introduce specific therapeutic
      interventions for each patient, thereby achieving safe and efficient swallowing,
      while prolonging oral feeding.

PMID- 15514896
TI  - [The prevalence of symptoms of anxiety and depression in female migraine
      sufferers].
AB  - INTRODUCTION: The comorbidity migraine and mental disorder is high, specially,
      anxiety and depressive disorders. Aim. To establish the prevalence of anxiety and
      depressive symptoms in a clinical population of women who suffered from migraine.
      PATIENTS AND METHODS: We included women with migraine over 18 years old, no
      pregnant and without psychiatric history. We quantified anxiety and depressive
      symptom with Zung's self-reporting scales. RESULTS: A group of 110 women was
      studied, mean age was 34.4 years (SD 9.4); average scholarity was 9.1 years (SD
      4.5); 72.7% was married, and 46.9% was housewife. 68.2% suffered from migraine
      with aura and 31.6% migraine without aura. 70.0% presented anxiety and 52.7%
      depression clinically important. Average Zung' scores for anxiety was 53.9 (SD
      7.9) and for depression was 51.0 (SD 9.5). It was significant comorbidity
      migraine associated with anxiety and depression. CONCLUSIONS: The prevalence of
      anxiety and depression is high among women with migraine. It was independent of
      age, scholarity, marital status, occupation and sort of migraine. It is frequent
      comorbidity anxiety and depressive symptoms among women with migraine.

PMID- 15514897
TI  - [Dysautonomic seizures in patients admitted to an intensive care unit following
      severe traumatic brain injury].
AB  - AIM: To describe clinical and radiologic features of dysautonomic crisis after
      severe traumatic brain injury and its influence in the clinical situation six
      months later. PATIENTS AND METHODS: Retrospective, observatory study of seven
      patients after severe head injury, with dysautonomic crisis, admitted in the
      Critical Care Unit (CCU) during six months. No interventions. Its clinical
      features, its association with intracranial pressure and the treatment for
      Dysautonomic crisis they have received were extracted from the computed clinical
      report. We have evaluated his neurologic prognosis with the Jennet-Bond scale and
      his radiologic characteristics with the Gennarelly scale. RESULTS: Dysautonomic
      crisis began in the first week if the patients didn't received neuromuscular
      blocks drugs and they continued when the patients were discharged from the CCU in
      a young population with an initial Glasgow scale coma of 5 points. We didn't wait
      a special radiologic pattern. After the next six months, crisis were disappeared
      in 86% of patients and all patients reached a good neurologic level in the Jennet
      Bond scale. CONCLUSIONS: Dysautonomic crisis appeared early in young men after
      severe head injury. We didn't find a radiologic pattern that predisposes the
      dysautonomic crisis. They didn't interfere the recovering six months after head
      injury.

PMID- 15514898
TI  - [Does brain blood flow HMPAO SPECT withhold the vascular etiopathogenic theory of
      transient global amnesia?].
AB  - INTRODUCTION: Transient global amnesia (TGA) is a neurological disorder that
      consists in a sudden loss of anterograd memory and temporospatial disorientation
      during less than 24 hours. Several precipitating factors have been reported.
      Conventional neuroimaging scans usually are negative. Different etiopathogenic
      theories have been postulated but the vascular etiology is the most commonly
      accepted. CASE REPORTS: Three patients with a typical presentation of TGA are
      studied. In all of them two brain blood flow HMPAO SPECT were performed, within
      the first 48 hours from the onset and three months after as an evolutive control.
      The first patient showed a left temporal perfusion defect and temporoparietal
      hypoperfusion. The second showed frontotemporal hypoperfusion, temporal mesial
      defect and hypoperfusion in basal ganglia, all in the left side. The third
      patient showed thalamic hyperperfusion and cerebellum hypoperfusion, both in the
      left. In all of them, control SPECT normalized. CONCLUSION: Three etiopatogenic
      theories about TGA have been reported: epilepsy, migraine and blood flow
      impairment. In TGA neuroanatomic image and neurophysiologic studies usually do
      not show significative alterations. Conversely, functional studies as brain blood
      flow HMPAO SPECT, do show changes being the most common bilateral temporobasal
      hypoperfusion, although this is not the only pattern described. Causes of this
      variable behaviour remain unclear but can be related to different clinic
      expressions and, over all, to time of evolution from onset. The three cases in
      this study show three different perfusion patterns reported in TGA and all of
      them withhold the vascular etiopathogenic theory.

PMID- 15514899
TI  - [Hashimoto's encephalopathy associated with scleromyxedema: coincidental or the
      overlapping of two syndromes with a possible autoimmune origin?].
AB  - INTRODUCTION: The encephalopathies that may accompany Hashimoto's thyroiditis and
      scleromyxedema, both of which are diseases that probably have an autoimmune
      origin, are clinically similar. The presence of both Hashimoto's thyroiditis and
      scleromyxedema in a patient with encephalopathy led us to compare the clinical
      symptoms and the different possible mechanisms accounting for the pathology. CASE
      REPORT: We describe the case of a 54-year-old male who was admitted to hospital
      because of several occurrences of transient neurological focus that finally
      developed into a clinical picture of aphasia, acalculia and right homonymous
      hemianopsia. The patient had previously been diagnosed as suffering from
      scleromyxedema, which responded poorly to treatment, as well as IgG kappa
      paraproteinemia and, six months before admission to hospital, Hashimoto's
      thyroiditis. No abnormalities were found in the complementary tests, except for
      slightly high protein levels in the cerebrospinal fluid, a diffuse slowing of
      brain waves in the electroencephalogram and alterations due to thyroiditis and
      paraproteinemia. Neurological symptoms improved after a few days of corticoid
      therapy. CONCLUSIONS: The presentation of encephalopathy as a stroke and its
      excellent response to treatment with corticoids pointed to a case of Hashimoto's
      encephalopathy, although we cannot completely rule out the possibility of it
      being a dermato-neuro syndrome, which is associated to scleromyxedema. In this
      paper we review the different pathological mechanisms proposed for the two
      clinical entities, as well as the clinical features that are similar in both
      syndromes and which could be an indication of some common mechanism shared by
      them.

PMID- 15514900
TI  - [Clinical progress of neonatal non-ketotic hyperglycinemia under treatment].
AB  - INTRODUCTION: Non-ketotic hyperglycinemia is a congenital error in the breakdown
      of glycine. The most common type is the classical neonatal form, which begins at
      the age of a few days with symptoms of lethargy, hypotonia, myoclonia,
      convulsions, apneas and, frequently, ends in death. Survivors usually develop
      intractable epilepsy and mental retardation. There is no effective treatment for
      this condition, but trials have been carried out with a therapy that diminishes
      the levels of glycine, benzoate (BZ), and another that blocks the excitatory
      effect in N-methyl-D-aspartate receptors: dextromethorphan (DTM). CASE REPORT: We
      report on the progress of a classical neonatal case, which began at the age of a
      few hours with hypotonia and stupor, without myoclonias or seizures, but with a
      suppression wave trace on the electroencephalogram (EEG). Cerebrospinal fluid
      (CSF) showed glycine levels of 141 micromol/L (the normal level is 6.66 +/- 2.66
      micromol/L), with a CSF/plasma ratio of 0.19 (the normal ratio is < 0.02).
      Treatment was started on the thirteenth day with BZ and DTM, and alertness and
      eye fixation improved in just three days; at the same time the EEG readings
      become normal. The glycine level in plasma returned to normal at two months and
      that in CSF was considerably reduced, although with CSF/plasma levels that were
      still high. At present the patient is 4 years old, has never had convulsions, EEG
      results have always been normal, and continues with BZ, DTM, carnitine and diet.
      The patient has presented a high degree of hypermotoric behaviour, but is
      currently more attentive and more sociable, has been walking from the age of 35
      months and has a quotient in the different areas of development of 40-50.
      CONCLUSIONS: The clinical progress made by our patient could be said to be
      anything but negligible, and we therefore recommend that treatment should be
      started as early as possible after diagnosis.

PMID- 15514901
TI  - [Cerebral haemorrhage in Sneddon's syndrome: case report and literature review].
AB  - INTRODUCTION: Sneddon's syndrome is the association between livedo reticularis
      and stroke. Hemorrhagic strokes in Sneddon's syndrome are exceptional. CASE
      REPORT: A 39-year-old woman who had had a livedo reticularis for about 14 years
      attended the Emergency Unit complaining of sudden, severe headache and numbness
      and weakness in her left extremities. Physical examination revealed left
      supranuclear facial palsy and left crural hemiparesis and hemihypoalgesia.
      Cranial CT showed a right parieto-occipital lobar haemorrhage. Immunological
      studies, including antiphospholipid antibodies, were negative. A cerebral
      angiography showed anomalies in most distal branches of intracranial arteries.
      Biopsies of the skin and digital arteries yielded non conclusive results.
      CONCLUSION: The association between livedo reticularis and stroke, together with
      the angiographic findings led us to the diagnosis of Sneddon's syndrome. When
      comparing our case with similar ones, we must point out to its onset with a
      hemorrhagic stroke and to the lobar location of the bleeding.

PMID- 15514902
TI  - [Schilder's disease: two new cases and a review of the literature].
AB  - INTRODUCTION: Schilder's disease, or diffuse myelinoclastic sclerosis, is an
      infrequent disease that presents clinically as a pseudotumoural demyelinating
      lesion, which makes its diagnosis more complicated as it can be mistaken for a
      tumour or an abscess. CASE REPORTS: We examine the case of a male who was healthy
      up to the age of 8 years, when symptoms of a left hemiparesis appeared with a
      subacute onset and which were associated to symptoms of intracranial
      hypertension. A brain CAT scan showed a hypodense lesion in the right
      temporoparietal region, and the hypothesis of a tumoural lesion (astrocyte) was
      suggested. Treatment was started with dexamethasone and furosemide, and a
      complete regression of the symptoms and a considerable decrease in the cerebral
      lesion were observed. The second case is that of a female adolescent who, at the
      age of 11, developed a clinical picture of subacute onset of left hemiplegia. A
      brain CAT scan revealed hypodense lesions with ring-shaped contrast enhancement.
      In view of the histological diagnosis of an astrocyte, radiotherapy and
      corticotherapy are started. After two months' treatment, a sharp involution of
      the lesions was observed, which led to the acceptance of the diagnostic
      hypothesis of Schilder's disease. Both children presented recurrence of the
      lesions three years and nine months, in the first and second case respectively,
      after the first episode. Treatment with corticoid therapy was started and gave
      good clinical and radiological responses. CONCLUSIONS: In the presence of a
      neurological deficit with a subacute onset, associated to a brain image showing a
      'tumoural' lesion containing an important amount of oedema and little mass
      effect, diagnoses other than that of a brain tumour must be taken into account.
      It thus becomes possible to avoid invasive forms of treatment, such as surgical
      resection, which entail a number of sequelae.

PMID- 15514903
TI  - [Perspectives in the treatments of poisonings by organophosphorus insecticides
      and warfare nerve agents].
AB  - INTRODUCTION AND DEVELOPMENT: Organophosphorus compounds are worldwide employed
      as insecticides and are yearly responsible of several millions of poisonings. The
      chemical structure of most of the warfare nerve agents also corresponds with an
      organophosphorus compound. Organophosphorus insecticides and warfare nerve agents
      exert their main toxicological effects through inhibition of
      acetylcholinesterase. Current treatments of patients poisoned with
      organophosphorus compounds include atropine (in order to protect muscarinic
      receptors), oximes (in order to accelerate the reactivation of the inhibited
      acetylcholinesterase) and benzodiazepines (in order to avoid convulsions). The
      administration of phosphotriesterases (enzymes involved in the detoxication of
      organophosphorus compounds through hydrolysis) is a very effective treatment
      against poisonings by organophosphorus insecticides and warfare nerve agents.
      There are experimental preventive treatments based on the simultaneous
      administration of carbamates and certain antimuscarinic drugs, different from
      atropine, which notably improve the efficacy of the classical treatments applied
      after poisonings by warfare nerve agents. CONCLUSIONS: The treatments based in
      the administration of phosphotriesterases might be the response to the call of
      the World Health Organization for searching new treatments with capability to
      reduce the high mortality recorded in the cases of poisonings by organophosphorus
      compounds. These treatments can be applied in a preventive way without the
      intrinsic neurotoxicity associated to the preventive treatments based on
      carbamates and antimuscarinic drugs. Therefore, these treatments are specially
      interesting for people susceptible to suffer severe exposures, i.e. sprayers in
      the farms.

PMID- 15514904
TI  - [The biophysical foundations of the localisation of encephalogram generators in
      the brain. The application of a distribution-type model to the localisation of
      epileptic foci].
AB  - INTRODUCTION: The brain electrical activity measured as the EEG signal is a
      powerful tool for the understanding of normal and pathological brain function.
      The EEG presents a high temporal resolution but a low spatial resolution. The
      latter can be improved solving the so-called inverse problem, if some a priori
      physiological and anatomical information is included. DEVELOPMENT: The present
      review presents the biophysical bases that allows brain source localization in
      realistic head models, as well as the two basic source models used: dipolar
      models and distributed source models. Finally, an example of practical
      application for the localization of epileptic focus using the distributed
      solution EPIFOCUS will be presented.

PMID- 15514905
TI  - [Clinical techniques for use in neurological physical examinations. I. General
      organisation, cranial and peripheral spinal nerves].
AB  - AIMS: The purpose of this work is to focus on the main practical aspects of the
      techniques used for the physical examination of the nervous system and to present
      an approach for the practice of this study in adult patients. DEVELOPMENT: We
      recommend clinicians to carry out a brief but consistent and effective
      exploration in a systematic, flexible and orderly manner to check for alterations
      in the functioning of the nervous system. Should any anomalies be detected, then
      a more detailed and thorough neurological exploration must be performed
      selectively. The techniques and data from this examination are organised into
      five broad categories: mental status, cranial nerves, motor function, reflex
      function and sensory function. The practical aspects of the main techniques used
      in the physical exploration are reviewed and we also describe the technique to be
      employed for palpating the main peripheral nerves. CONCLUSIONS: The study offers
      a detailed description of the chief clinical techniques used in the physical
      exploration of the cranial nerves and for the palpation of the peripheral nerves;
      we also present an approach to performing the neurological examination.
      Furthermore, we highlight the importance of physically examining the nervous
      system in contemporary medicine and the need to continually perfect the way these
      techniques are performed in order to achieve an efficient clinical practice.

PMID- 15514906
TI  - [A century of barbiturates in neurology].
AB  - INTRODUCTION AND AIMS: Until the early 20th century, pharmacological treatments
      for neurological disorders were scarce and inefficient; only bromides stood out
      as sedating and antiepileptic agents. DEVELOPMENT: The introduction of
      barbiturates for clinical use in 1904 heralded the beginning of a new age in the
      pharmacological management of certain neurological pathologies. In this study, we
      analyse the historical process of the discovery and use of barbiturates in the
      field of neurology, from the moment it was started by von Baeyer in 1864, with
      the synthesis of malonylurea, up to the period of the decline of barbiturate
      therapy in the 1960s. In 1903, von Mering and Fischer discovered the hypnotic
      properties of barbital and later synthesised phenobarbital (1911). In the years
      that followed a number of barbiturates, such as butobarbital, amobarbital,
      secobarbital, pentobarbital, thiopental, and so on, were gradually incorporated
      into the therapeutic arsenal. During this period, the different therapeutic uses
      of barbiturates in neurology were analysed, from their traditional use as
      hypnotic agents (von Husen) to the discovery of the anticonvulsant properties of
      phenobarbital (Hauptmann) and its use in the treatment of epilepsy. CONCLUSIONS:
      The barbiturates were one of the first pharmacological tools that proved to be
      really effective in the management of some neurological disorders. Nevertheless,
      problems associated with their safety (dependence phenomena and deaths from
      overdoses), together with the introduction of numerous psychopharmacological
      agents in the 1950s, ended up eclipsing the use of barbiturates, except for a few
      very specific cases in which they are still indicated.

PMID- 15514907
TI  - [Pituitary abscess following the removal of a pituitary adenoma].

PMID- 15514909
TI  - [Reibergram for immunoglobulin E intrathecal synthesis evaluation].

PMID- 15514910
TI  - [Intracerebral hemorrhage associated with a nightmare. Case report].

PMID- 15514911
TI  - [Fever and brain haemorrhage: an angiographic diagnosis].

PMID- 15514912
TI  - [Malignant fibrous histiocytoma of the meninges].

PMID- 15514915
TI  - Pediatric melanoma.

PMID- 15514916
TI  - Osteonecrosis: a treatment related toxicity in childhood acute lymphoblastic
      leukemia (ALL)--experiences from trial ALL-BFM 95.
AB  - BACKGROUND: Osteonecrosis (ON) as a complication during treatment of acute
      lymphoblastic leukemia (ALL) has gained rising attention over the past decade.
      Corticosteroids, representing an essential element of antileukemic therapy, are
      known to induce ON, which in turn may cause significant morbidity. Due to
      spontaneous reporting of affected patients with ON, a group-wide evaluation was
      performed to determine incidence, risk factors, and morbidity for ON. PROCEDURE:
      Patients were identified via spontaneous reporting to the study center and via
      questionnaire, addressing all 64 participating centers. We retrospectively
      analyzed 1,951 patients below 18 years of age who were treated according to trial
      ALL-BFM 95 between 01.01.1996 and 30.06.2000. RESULTS: Thirty-one patients (14
      male, 17 female) affected by ON were identified. The overall 5-year cumulative
      incidence for ON is 1.8%. The incidence for patients <10 years is 0.2%, whereas
      for patients >/=10 years it is 8.9% (P = 0.00) and 16.7% (P = 0.003) for patients
      >/=15 years. The majority (n = 20) showed ON in two or more joints, and the
      joints most commonly affected were knees (14 patients, 24 affected knees) and
      hips (11 patients, 20 affected joints). Thirteen out of 31 patients had to
      undergo surgery in the course of their disease. CONCLUSIONS: Symptomatic ON is a
      rare event in patients treated with BFM-type chemotherapy with an overall 5-year
      cumulative incidence of 1.8%. The age group >/=10 years, and particularly
      adolescents >/=15 years have a significantly higher risk of developing ON.

PMID- 15514917
TI  - A comparison of self-reported satisfaction between adolescents treated in a
      "teenage" unit with those treated in adult or paediatric units.
AB  - BACKGROUND: Despite recommendations that adolescents should have in-patient
      management amongst their peers, there is little literature to support this. The
      study aim was to evaluate and contrast patient satisfaction for teenage cancer
      patients treated in two settings. The first is a split site unit (a paediatric
      ward and adult cancer centre in different locations within one city) and the
      second, a dedicated adolescent unit for patients aged 13-20. PROCEDURE: Eligible
      patients aged 13-20 years received treatment from September 1997 to June 2000 and
      totalled sixty-five adolescents. The patients were identified at both centres
      from departmental databases. Postal questionnaires (the Youth Satisfaction
      Questionnaire) were sent to those eligible. RESULTS: Patients receiving treatment
      in the teenage cancer unit (TCU) were not significantly more satisfied overall
      than those receiving treatment in adult or paediatric units. However, significant
      differences were noted in: recreational and relaxation facilities (P < 0.005, P <
      0.0002), studying space (P < 0.004), ward noise (P < 0.02), and company of the
      same age (P < 0.0001). The Grade Point Average (a score of all specific items)
      was higher in favour of the TCU (P < 0.03). Patients at both centres were
      dissatisfied with hospital food and menus offered. CONCLUSIONS: Adolescents with
      cancer are satisfied with the overall care they receive independent of whether it
      is a TCU or a split site unit. Teenagers are significantly more satisfied with
      environmental aspects of care in the TCU. More research is required to establish
      the correct provision for teenagers with cancer. This is the first study that
      contrasts satisfaction between different centres and thus adding to an
      understanding of the needs of teenagers with cancer.

PMID- 15514918
TI  - Neurofibromatosis type 1 and multiple primary malignancies.

PMID- 15514919
TI  - Relationship of tyrosine hydroxylase and serotonin immunoreactivity to
      sensorimotor circuitry in larval zebrafish.
AB  - Our previous study tracked the ontogeny of aminergic systems in zebrafish (Danio
      rerio). Here we use tyrosine hydroxylase (TH) and serotonin (5-hydroxytryptamine;
      5-HT) immunoreactivity, in conjunction with retrograde and genetic labeling
      techniques, to provide a more refined examination of the potential synaptic
      contacts of aminergic systems. Our focus was on different levels of the
      sensorimotor circuit for escape, from sensory inputs, through identified
      descending pathways, to motor output. We observed 5-HT reactivity in close
      proximity to the collaterals of the Rohon-Beard sensory neurons in spinal cord.
      In the brainstem we found TH and 5-HT reactivity closely apposed to the dendritic
      processes of the nucleus of the medial longitudinal fascicle (nMLF), in addition
      to the ventral dendrites of the Mauthner neuron and its serial homologs MiD2cm
      and MiD3cm. Only TH reactivity was observed near the lateral dendrites of the
      Mauthner cell. TH and 5-HT reactivity were also positioned near the outputs of
      reticulospinal cells in spinal cord. Finally, both TH and 5-HT reactivity were
      detected close to the dendritic processes of primary and secondary spinal motor
      neurons. We also confirmed, using dual TH and 5-HT staining and retrograde
      labeling, that the sources of spinal aminergic reactivity include the posterior
      tuberculum (dopamine) and inferior raphe region (5-HT). Our data indicate that
      aminergic systems may interact at all levels of the sensorimotor pathways
      involved in escape. The identification of some of these likely sites of aminergic
      action will allow for directed studies of their functional roles using the
      powerful combination of techniques available in zebrafish.

PMID- 15514920
TI  - Differential expression of synapsin in visual neurons of the locust Schistocerca
      gregaria.
AB  - In many taxa, photoreceptors and their second-order neurons operate with graded
      changes in membrane potential and can release neurotransmitter tonically. A
      common feature of such neurons in vertebrates is that they have not been found to
      contain synapsins, a family of proteins that indicate the presence of a reserve
      pool of synaptic vesicles at synaptic sites. Here, we provide a detailed analysis
      of synapsin-like immunoreactivity in the compound eye and ocellar photoreceptor
      cells of the locust Schistocerca gregaria and in some of the second-order
      neurons. By combining confocal laser scanning microscopy with electron
      microscopy, we found that photoreceptor cells of both the compound eye and the
      ocellus lacked synapsin-like immunostaining. In contrast, lamina monopolar cells
      and large ocellar L interneurons of the lateral ocellus were immunopositive to
      synapsin. We also identified the output synapses of the photoreceptors and of the
      L interneurons, and, whereas the photoreceptor synapses lacked immunolabeling,
      the outputs of the L interneurons were clearly labeled for synapsin. These
      findings suggest that the photoreceptors and the large second-order neurons of
      the locust differ in the chemical architecture of their synapses, and we propose
      that differences in the time course of neurotransmission are the reason for this.

PMID- 15514921
TI  - Differentiation and tropic/trophic effects of exogenous neural precursors in the
      adult spinal cord.
AB  - The fate of exogenous neural stem cells (NSCs) in the environment of the adult
      nervous system continues to be a matter of debate. In the present study, we
      report that cells of the murine NSC clone C17.2, when grafted into the lumbar
      segments of the spinal cord of adult rats, survive and undergo partial
      differentiation. C17.2 cells migrate avidly toward axonal tracts and nerve roots
      and differentiate into nonmyelinating ensheathing cells. Notably, C17.2 cells
      induce the de novo formation of host axon tracts aiming at graft innervation.
      Differentiation and inductive properties of C17.2 cells are independent of the
      presence of lesions in the spinal cord. The tropic/trophic interactions of C17.2
      NSCs with host axons, the avid C17.2 cell-host axon contacts, and the ensheathing
      properties of these cells are related to their complex molecular profile, which
      includes the expression of trophic cytokines and neurotrophins such as glial cell
      line-derived neurotrophic factor and brain-derived neurotrophic factor, glial
      growth factor receptors such as ErbB-2; and PASK, the mammalian homologue of the
      fray gene that is involved in axon ensheathment. These results show that NSCs
      might not only play a critical supportive role in repairing axonal injury in the
      adult spinal cord but also can be used as probes for exploring the molecular
      underpinnings of the regenerative potential of the mature nervous system after
      injury.

PMID- 15514923
TI  - RNA binding motif (RBM) proteins: a novel family of apoptosis modulators?
AB  - RBM5 is a known modulator of apoptosis, an RNA binding protein, and a putative
      tumor suppressor. Originally identified as LUCA-15, and subsequently as H37, it
      was designated "RBM" (for RNA Binding Motif) due to the presence of two RRM (RNA
      Recognition Motif) domains within the protein coding sequence. Recently, a number
      of proteins have been attributed with this same RBM designation, based on the
      presence of one or more RRM consensus sequences. One such protein, RBM3, was also
      recently found to have apoptotic modulatory capabilities. The high sequence
      homology at the amino acid level between RBM5, RBM6, and particularly, RBM10
      suggests that they, too, may play an important role in regulating apoptosis. It
      is the intent of this article to ammalgamate the data on the ten originally
      identified RBM proteins in order to question the existence of a novel family of
      RNA binding apoptosis regulators.

PMID- 15514924
TI  - Structural characterization and enantioseparation of the chiral compound
      praziquantel.
AB  - In this study, we aimed to characterize the chiral compound type of a leading
      antischistosomal drug, praziquantel. The optically pure praziquantel enantiomers
      were recovered from the racemic mixture by enantiomeric separation, which was
      performed on preparative scale chromatography by using a novel beta-cyclodextrin
      type chiral column. The thermodynamic properties of praziquantel were determined
      from differential scanning calorimetry and the physical properties were studied
      by examining Fourier transform infrared spectroscopy and X-ray powder
      diffraction. Based on the differential scanning calorimetry data, a melting point
      binary phase diagram was constructed. A ternary solubility phase diagram of
      praziquantel in methanol was also determined at the temperature of 0 degrees C.
      All the experimental results support the conclusion that praziquantel is a
      racemic compound. The characterization of physical properties of praziquantel and
      the phase diagram are crucial for understanding the rationality for the
      successful resolution of praziquantel and also provide the basis for designing
      the strategy of separation and recovery of pure enantiomer.

PMID- 15514925
TI  - Striking intrafamilial phenotypic variability and spastic paraplegia in the
      presence of similar homozygous expansions of the FRDA1 gene.
AB  - We report on a Friedreich's ataxia (FA) family with 3 affected siblings with
      markedly different phenotypic presentations, including one with spastic
      paraplegia. Molecular analysis showed midsize GAA repeat expansion sizes in all 3
      individuals. Gait spasticity in FA, although rare, has been described in a few
      patients who are compound heterozygotes for a point mutation, or who had GAA
      expansions of less than 200 repeats. The occurrence of spastic paraplegia in our
      family, in the presence of homozygous midsize GAA repeat expansions, is an
      unusual finding. Spasticity can be the main feature in both sporadic and familial
      patients with FA, either as an isolated finding, or in addition to other
      neurological abnormalities, and should be included as a rare feature in the
      clinical spectrum of FA. This family also demonstrates that in FA, marked
      intrafamilial phenotypic variability can arise in the presence of similar GAA
      expansion sizes. Therefore, in familial FA, the disease course in relatives
      therefore cannot be predicted solely from repeat length. Factors such as somatic
      mosaicism, repeat interruptions, modifying mutations and environmental factors
      must also be considered.

PMID- 15514926
TI  - Physical characterization of controlled release of paclitaxel from the TAXUS
      Express2 drug-eluting stent.
AB  - The polymer carrier technology in the TAXUS drug-eluting stent consists of a
      thermoplastic elastomer poly(styrene-b-isobutylene-b-styrene) (SIBS) with
      microphase-separated morphology resulting in optimal properties for a drug
      delivery stent coating. Comprehensive physical characterization of the stent
      coatings and cast film formulations showed that paclitaxel (PTx) exists primarily
      as discrete nanoparticles embedded in the SIBS matrix. Thermal and chemical
      analysis did not show any evidence of solubility of PTx in SIBS or of any
      molecular miscibility between PTx and SIBS. Atomic force microscope data images
      revealed for the first time three-dimensional stent coating surfaces at high
      spatial resolutions in air and in situ under phosphate-buffered saline as drug
      was released. PTx release involves the initial dissolution of drug particles from
      the PTx/SIBS coating surface. Morphological examination of the stent coatings in
      vitro supported an early burst release in most formulations because of surface
      PTx followed by a sustained slower release of PTx from the bulk coating. The in
      vitro PTx release kinetics were dependent on the formulation and correlated to
      the drug-to-polymer ratio. Atomic force microscopy analysis confirmed this
      correlation and further supported the concept of a matrix-based drug-release
      coating.

PMID- 15514927
TI  - Exchange transfusion with synthetic oxygen-carrying plasma protein "albumin-heme"
      into an acute anemia rat model after seventy-percent hemodilution.
AB  - Recombinant human serum albumin (rHSA) incorporating the synthetic heme "albumin
      heme" is an oxygen-carrying plasma protein that has the potential to be a red
      blood cell substitute. The physiological responses to a 30% exchange transfusion
      with two types of albumin-heme (rHSA-FecycP, rHSA-FepivP) solutions after 70%
      isovolemic hemodilution with 5 g/dL rHSA were investigated using anesthetized
      rats. The circulation parameters, blood parameters, renal cortical oxygen
      pressure (pO2), and muscle tissue pO2 were carefully monitored for 60 min after
      the injection. The declined mean arterial pressure and the mixed venous partial
      pO2 significantly recovered to 70.8 and 91.9% of the basal values by intravenous
      infusion of albumin-hemes, respectively. The lowered renal cortical pO2 also
      increased, indicating oxygen transport by this synthetic hemoprotein. The
      administration of albumin-heme into the acute anemia rat model after hemorrhage
      improved the circulatory volume and resuscitated the shock state. Both rHSA
      FecycP and rHSA-FepivP transported oxygen through the body.

PMID- 15514928
TI  - HLA-G gene activation in tumor cells involves cis-acting epigenetic changes.
AB  - The tissue distribution of HLA-G molecules is broader than originally reported in
      trophoblastic cells. On the basis of numerous studies, HLA-G is also expressed in
      malignant tumors and involved in tumor immune escape. The mechanisms of HLA-G
      gene regulation differ from those of classical HLA class I genes and involve
      epigenetic processes. Here, we provide additional evidence on the influence of
      DNA demethylation on HLA-G activation. We also analyze the 5' regulatory region
      of HLA-G in 2 cellular models, melanoma (FON, M8) and choriocarcinoma (JEG-3,
      JAR), either expressing HLA-G transcripts or not. The data strongly suggest that
      HLA-G is silenced as a result of CpG site hypermethylation within a 5' regulatory
      region encompassing 450 bp upstream of the start codon, whereas it is activated
      upon demethylation. This result correlates with the acetylation status of
      histones within this region and the putative locus control region located at -1.2
      kb. cis-acting epigenetic changes and the fact that demethylating agents activate
      HLA-G expression at least 5 days following treatment should be taken into account
      in epigenetic cancer therapies.

PMID- 15514929
TI  - Dorsal root ganglion neurons up-regulate the expression of laminin-associated
      integrins after peripheral but not central axotomy.
AB  - The favorable prognosis of regeneration in the peripheral nervous system after
      axonal lesions is generally regarded as dependent on the Schwann cell basal
      lamina. Laminins, a heterotrimeric group of basal lamina molecules, have been
      suggested to be among the factors playing this supportive role. For neurons to
      utilize laminin as a substrate for growth, an expression of laminin binding
      receptors, integrins, is necessary. In this study, we have examined the
      expression of laminin binding integrin subunits in dorsal root ganglion (DRG)
      neurons after transection to either their peripherally projecting axons, as in
      the sciatic nerve, followed by regeneration, or the centrally projecting axons in
      dorsal roots, followed by no or weak regenerative activity. In uninjured DRG,
      immunohistochemical staining revealed a few neurons expressing integrin subunit
      alpha6, whereas integrin subunits alpha7 and foremost beta1 were expressed in a
      majority of neurons. After an injury to the sciatic nerve, mRNAs encoding all
      three integrins were up-regulated in DRG neurons. By anterograde tracing,
      immunoreactivity for all studied integrins was also found in association with
      growing axons after a sciatic nerve crush lesion in vivo. In contrast, mRNA
      levels remained constant in DRG neurons after a dorsal root injury. Together with
      previous findings, this suggests that integrin subunits alpha6, alpha7, and beta1
      have an important role in the regenerative response following nerve injury and
      that the lack of regenerative capacity following dorsal root injury could in part
      be explained by the absence of response in integrin regulation.

PMID- 15514930
TI  - Urocortinergic neurons respond in a differentiated manner to various acute
      stressors in the Edinger-Westphal nucleus in the rat.
AB  - Corticotropin-releasing factor (CRF) was implicated as being a major contributor
      to the neurochemically mediated central regulation of stress response; however,
      an increasing body of evidence suggests that, besides CRF, other members of this
      neuropeptide family, such as urocortin (Ucn), may also play a role in modifying
      the efferent components of immune, endocrine, and behavioral responses to stress.
      Ucn's distribution in the rat brain has been demonstrated, with the most abundant
      Ucn-immunoreactive perikarya present in the Edinger-Westphal nucleus (E-WN).
      Acute pain and immobilization stresses recruit E-WN neurons, however, the
      activation pattern of E-WN Ucn neurons in response to various acute systemic and
      neurogenic challenges has not been compared in a single study. We therefore
      combined quantitative Fos imaging as a marker for neuronal activation with
      urocortin immunohistochemistry to visualize neurons induced by intravenous
      lipopolysaccharide (LPS; 100 microg/kg), ether inhalation, restraint,
      hyperosmotic (1.5 M NaCl i.p.), and hypotensive hemorrhage challenges. Neurons in
      the E-WN responded with the strongest Fos induction to LPS, but ether and
      restraint stress also resulted in massive Fos immunoreactivity 2 hours after
      stress. Unexpectedly, hyperosmotic and hypotensive hemorrhage stresses did not
      induce urocortinergic perikarya in this brain area 2 hours poststress. This
      challenge-specific recruitment of E-WN neurons was independent of stress-induced
      adrenal response. The biological significance and the stress-specific activation
      of E-WN urocortinergic neurons will be discussed.

PMID- 15514931
TI  - Experimental study of the connections of the telencephalon in the rainbow trout
      (Oncorhynchus mykiss). II: Dorsal area and preoptic region.
AB  - In this study and the accompanying article (Folgueira et al., 2004a), the
      fluorescent carbocyanine dye 1,1'-dioctadecyl 3,3,3',3'
      tetramethylindocarbocyanine perchlorate (DiI) was used in fixed tissue to
      comprehensively analyze the connections of the different regions of the
      telencephalic lobes and the preoptic region of the rainbow trout. Here, we
      analyze the connections of the dorsal area (D; pallium) of the telencephalon, and
      the preoptic region, as well as the telencephalic connections of several
      structures in the diencephalon and brainstem of juvenile trout. The dorsal plus
      dorsolateral pallial zone of D (Dd+Dl-d) receives afferents from contralateral
      Dd+Dl-d, the ventral area of the telencephalon, preoptic nucleus, suprachiasmatic
      nucleus, medial thalamus, preglomerular complex, anterior and lateral tuberal
      nuclei, posterior tuberal nucleus, posterior hypothalamic lobe, superior raphe
      nucleus, and the rhombencephalic central gray and reticular formation, and
      projects to the central zone of D (Dc), medial thalamus, and some caudomedial
      hypothalamic regions. The medial zone of D (Dm) maintains reciprocal connections
      with the preglomerular complex and also receives afferents from the preoptic
      nucleus, suprachiasmatic nucleus, anterior tuberal nucleus, preglomerular
      tertiary gustatory nucleus, posterior tubercle, superior raphe nucleus, locus
      coeruleus, and the rhombencephalic central gray, and reticular formation. Dc
      receives fibers mainly from Dd+Dl-d, preoptic nucleus, preglomerular complex, and
      torus semicircularis and projects to several extratelencephalic centers,
      including the paracommissural nucleus, optic tectum, torus semicircularis,
      thalamus, preglomerular complex, posterior tubercle nuclei, and inferior
      hypothalamic lobes. The posterior zone of D (Dp) is mainly connected with the
      olfactory bulbs, the ventral and supracommissural nuclei of the ventral area
      (subpallium), the preoptic nucleus, and the preglomerular complex and projects to
      wide hypothalamic and posterior tubercular regions. The preoptic nucleus projects
      to the olfactory bulb, to most regions of the telencephalic lobes, and to several
      diencephalic and brainstem structures. These results reveal complex and
      specialized connectional patterns in the rainbow trout dorsal telencephalon and
      preoptic region. Most of these connections have not been described previously in
      salmonids. These connections indicate that the salmonid telencephalon is involved
      in multisensorial processing and modulation of brain activity.

PMID- 15514932
TI  - Afferent projections to nucleus reuniens of the thalamus.
AB  - The nucleus reuniens (RE) is the largest of the midline nuclei of the thalamus
      and the major source of thalamic afferents to the hippocampus and parahippocampal
      structures. Nucleus reuniens has recently been shown to exert powerful excitatory
      actions on CA1 of the hippocampus. Few reports on any species have examined
      afferent projections to nucleus reuniens. By using the retrograde anatomical
      tracer Fluorogold, we examined patterns of afferent projections to RE in the rat.
      We showed that RE receives a diverse and widely distributed set of afferents
      projections. The main sources of input to nucleus reuniens were from the
      orbitomedial, insular, ectorhinal, perirhinal, and retrosplenial cortices;
      CA1/subiculum of hippocampus; claustrum, tania tecta, lateral septum, substantia
      innominata, and medial and lateral preoptic nuclei of the basal forebrain; medial
      nucleus of amygdala; paraventricular and lateral geniculate nuclei of the
      thalamus; zona incerta; anterior, ventromedial, lateral, posterior,
      supramammillary, and dorsal premammillary nuclei of the hypothalamus; and ventral
      tegmental area, periaqueductal gray, medial and posterior pretectal nuclei,
      superior colliculus, precommissural/commissural nuclei, nucleus of the posterior
      commissure, parabrachial nucleus, laterodorsal and pedunculopontine tegmental
      nuclei, nucleus incertus, and dorsal and median raphe nuclei of the brainstem.
      The present findings of widespread projections to RE, mainly from limbic/limbic
      associated structures, suggest that nucleus reuniens represents a critical relay
      in the transfer of limbic information (emotional/cognitive) from RE to its major
      targets, namely, to the hippocampus and orbitomedial prefrontal cortex. RE
      appears to be a major link in the two-way exchange of information between the
      hippocampus and the medial prefrontal cortex.

PMID- 15514933
TI  - Neurokinin B-producing projection neurons in the lateral stripe of the striatum
      and cell clusters of the accumbens nucleus in the rat.
AB  - Neurons producing preprotachykinin B (PPTB), the precursor of neurokinin B,
      constitute 5% of neurons in the dorsal striatum and project to the substantia
      innominata (SI) selectively. In the ventral striatum, PPTB-producing neurons are
      collected mainly in the lateral stripe of the striatum (LSS) and cell clusters of
      the accumbens nucleus (Acb). In the present study, we first examined the
      distribution of PPTB-immunoreactive neurons in rat ventral striatum and found
      that a large part of the PPTB-immunoreactive cell clusters was continuous to the
      LSS, but a smaller part was not. Thus, we divided the PPTB-immunoreactive cell
      clusters into the LSS-associated and non-LSS-associated ones. We next
      investigated the projection targets of the PPTB-producing ventral striatal
      neurons by combining immunofluorescence labeling and retrograde tracing. After
      injection of Fluoro-Gold into the basal component of the SI (SIb) and medial part
      of the interstitial nucleus of posterior limb of the anterior commissure, many
      PPTB-immunoreactive neurons were retrogradely labeled in the LSS-associated cell
      clusters and LSS, respectively. When the injection site included the ventral part
      of the sublenticular component of the SI(SIsl), retrogradely labeled neurons
      showed PPTB-immunoreactivity frequently in non-LSS-associated cell clusters.
      Furthermore, these PPTB-immunoreactive projections were confirmed by the double
      fluorescence method after anterograde tracer injection into the ventral striatum
      containing the cell clusters. Since the dorsalmost part of the SIsl is known to
      receive strong inputs from PPTB-producing dorsal striatal neurons, the present
      results indicate that PPTB-producing ventral striatal neurons project to basal
      forebrain target regions in parallel with dorsal striatal neurons without
      significant convergence.

PMID- 15514934
TI  - An experimental study of the connections of the telencephalon in the rainbow
      trout (Oncorhynchus mykiss). I: Olfactory bulb and ventral area.
AB  - The fluorescent carbocyanine dye 1,1'-dioctadecyl 3,3,3',3'
      tetramethylindocarbocyanine perchlorate (DiI) was used in fixed tissue to
      comprehensively analyze the connections of the olfactory bulbs and the different
      regions of the ventral (V) area of the telencephalic lobes (subpallium) of the
      rainbow trout. With this goal, DiI was applied to the different telencephalic
      nuclei and zones, as well as to the olfactory nerve, the olfactory bulb, the
      retina, and to several structures in the diencephalon and brainstem of juvenile
      trout. The olfactory bulbs maintain reciprocal connections with several regions
      of the telencephalon [ventral nucleus of V (Vv), supracommissural nucleus (Vs),
      posterior zone of D (Dp), preoptic nucleus], and also project to the diencephalon
      (posterior tuberal nucleus, posterior hypothalamic lobe). Vv receives afferents
      from Vs, the dorsal nucleus of V (Vd), the preoptic nucleus, and from several
      nuclei in the diencephalon and brainstem (suprachiasmatic nucleus, anterior and
      lateral tuberal nuclei, preglomerular complex, tertiary gustatory nucleus,
      posterior tubercle, inferior hypothalamic lobes, thalamus, torus semicircularis,
      secondary gustatory nucleus, locus coeruleus, superior raphe nucleus, central
      gray, and reticular formation), and projects to dorsal (pallial) regions and most
      of the nuclei afferent to Vv. The dorsal nucleus of V (Vd) and Vs mainly project
      to the dorsal area. In an accompanying article (Folgueira et al., 2004), we
      present the results of application of DiI to dorsal (pallial) telencephalic
      regions, as well as of several experiments of tracer application to
      extratelencephalic regions. The results presented here, together with those of
      the accompanying article, reveal a complex connectional pattern of the rainbow
      trout ventral telencephalon, most of these connections having not been described
      previously in salmonids.

PMID- 15514935
TI  - Local and global chemotopic organization: general features of the glomerular
      representations of aliphatic odorants differing in carbon number.
AB  - To determine whether there is a general strategy used by the olfactory system to
      represent odorants differing in carbon chain length, rats were exposed to
      homologous series of straight-chained, saturated aliphatic aldehydes, ethyl
      esters, acetates, ketones, primary alcohols, and secondary alcohols (32 odorants
      total). Neural activity across the entire glomerular layer of the olfactory bulb
      was mapped quantitatively by measuring uptake of [14C]2-deoxyglucose evoked by
      each odorant. Uptake was observed both in dorsal glomerular modules previously
      associated with the particular odorant functional groups and in more ventral and
      posterior modules. Aldehyde-evoked activity patterns were dominated by ventral
      modules that included the area receiving projections from octanal-responsive
      sensory neurons expressing the I7 odorant receptor. The dorsal area that has been
      the focus of optical imaging studies of aldehyde responses contained only minor
      activity. For all functional groups except for ketones, uptake within functional
      group-sensitive modules displayed local chemotopy, with longer odorants
      stimulating more ventral and rostral glomeruli. In more posterior regions,
      chemotopy was observed for all functional groups, again with uptake shifting
      ventrally and rostrally with increasing chain length. In addition to these local
      shifts in activity, correlations analysis of entire activity patterns revealed a
      global chemotopic organization for all odorant series, with each odorant evoking
      a pattern most similar to odorants possessing the same functional group but
      differing by only one carbon in length. Thus, global chemotopy and local modular
      chemotopy appear to be fundamental principles underlying the representation of
      odorants differing in carbon chain length.

PMID- 15514937
TI  - Conducting polymers grown in hydrogel scaffolds coated on neural prosthetic
      devices.
AB  - The conducting polymer polypyrrole (PPy) was electrochemically grown on hydrogel
      scaffolds deposited on the surface of microfabricated neural prosthetic devices.
      It is shown that the pyrrole monomer can be grown vertically through the hydrogel
      layer up to the surface without affecting the adjacent sites on the probes. The
      electrochemical properties of the conducting polymer-modified hydrogels were
      studied by impedance spectroscopy and cyclic voltammetry. It is also found that
      the conducting polymers could still be readily grown through the hydrogel after
      the microstructure is disrupted by freeze drying. Impedance measurements at the
      biologically important frequency of 1 kHz showed that the minimum impedance of
      this polymer-modified hydrogel was 7 kOmega. This is much lower than the minimum
      impedance of polypyrrole film ( approximately 100 kOmega).

PMID- 15514938
TI  - Structure formation in injectable poly(lactide-co-glycolide) depots. II. Nature
      of the gel.
AB  - The benzyl benzoate solutions of poly(D,L-lactide-co-glycolide), a random
      oriented synthesized copolymer with L/G ratio of 50:50, have been shown to form
      gels during aging and upon injection into buffer or water. The gelation
      properties influence drug release kinetics for these injectable, depot-forming
      solutions. In this article, we report on the mechanism of gelation. We find that
      only polymers that have a certain average block length of glycolide units form
      gels during aging as well as depots upon in vitro. Thus, gel formation is likely
      due to the formation of ordered solvated aggregates of blocky glycolide units.
      Rheometry, differential scanning calorimetry, and nuclear magnetic resonance were
      used to investigate the gelation kinetics and the polymer molecular parameters.
      Of all the polymers used, poly(lactide-co-glycolide)s with glycolide average
      block length <2.9 did not show any gelation behavior. The details of the gelation
      process are also solvent dependent.

PMID- 15514939
TI  - A novel high-specificity approach for colorectal neoplasia: Detection of K-ras2
      oncogene mutation in normal mucosa.
AB  - There is an important need for a high-specificity approach to colorectal cancer.
      Approximately 50% of colorectal tumors contain K-ras gene mutations, which occur
      as an early step in carcinogenesis. K-ras mutations were detectable not only in
      tumors but also in microscopically normal colorectal mucosa close to carcinomas
      in some patients with colorectal cancer. This is the first systematic analysis of
      K-ras mutations in normal colonic mucosa at multiple consistently-selected
      locations. A total of 480 normal colonic mucosal samples were obtained from 80
      subjects, including 65 patients with sporadic colorectal cancer and 15 controls
      in whom a colorectal neoplasm was ruled out endoscopically. Normal mucosal
      samples were obtained at multiple consistently-selected locations using biopsy
      forceps during colonoscopy. Mutant allele-specific amplification (MASA)-PCR was
      performed; this could detect a K-ras mutation in normal colonic mucosa even
      though it was only sparsely present. The K-ras mutation was found in
      histologically normal mucosa from colorectal cancer patients (20 of 65 cases; 41
      of 390 loci) by MASA-PCR, especially frequent (51%; 19 of 37 cases) when the
      tumor showed a K-ras mutation. In contrast, no mutation was found in normal
      mucosa from 15 controls (90 loci). K-ras mutation in normal mucosa showed a
      significant association with the presence of colorectal cancer (p = 0.008). The
      specificity of the MASA-PCR method for colorectal neoplasms was thus 100%. We
      conclude that detection of K-ras mutations in normal colonic mucosa might serve
      as a high-specificity approach to colorectal cancer.

PMID- 15514940
TI  - Impact of p53-based immunization on primary chemically-induced tumors.
AB  - In mice as well as humans, cytotoxic T lymphocytes (CTL) specific for wild-type
      sequence (wt) p53 peptides have been shown to react against a wide range of
      tumors, but not normal cells. As such, they are attractive candidates for
      developing broadly applicable cancer vaccines. Of particular interest is the
      potential of using p53-based vaccines in high-risk individuals to prevent cancer.
      Methylcholanthrene, an immunosuppressive polycyclic hydrocarbon carcinogen
      implicated as a causative agent in human cancers, has long been used to induce
      murine tumors with a high incidence of genetic alterations and sensitivity to wt
      p53-specific CTL. To analyze the potential of p53-based vaccines on primary
      tumors, we evaluated the efficacy of DNA and dendritic cell vaccines targeting wt
      p53 peptides given to methylcholanthrene-treated mice in the protection or
      therapy settings. The results indicate that the efficacy of these vaccines
      relative to reducing tumor incidence were severely compromised by vaccine-induced
      tumor escape. As compared to tumors induced in non-immunized mice, a higher
      incidence of epitope-loss tumors was detected in tumors from the immunized mice.
      The increase in tumor escape arose as a consequence of either increased
      frequencies of mutations within/flanking p53 epitope-coding regions or
      downregulation of expression of the major histocompatibility complex Class I
      molecules that present these epitopes for T cell recognition These findings are
      consistent with current views of immunoselection occurring in patients receiving
      tumor peptide-based immunotherapy, and impact on the design and implementation of
      p53-based vaccines, in particular, those aimed at treating individuals at high
      risk for developing cancer.

PMID- 15514941
TI  - In vivo echographic evidence of tumoral vascularization and microenvironment
      interactions in metastatic orthotopic human neuroblastoma xenografts.
AB  - Human neuroblastoma (NB) is the second most frequent solid tumor of childhood and
      represents a highly heterogeneous disease at clinical and biologic levels. Little
      progress has been made to improve the poor prognosis of patients with high-stage
      NB. Tumor progression and metastatic dissemination still represent major
      obstacles to the successful treatment of advanced stage disease. In order to
      develop and evaluate new, targeted, therapeutic strategies, fully defined and
      biologically relevant in vivo models of NB are strongly needed. We have developed
      an orthotopic model of metastatic human NB in the nude mouse, using 2 well
      characterized NB cell lines. Tumor growth, vascular properties and metastatic
      patterns were investigated using a sensitive and newly developed in vivo
      echographic technology in addition to immunohistochemistry and PCR analyses.
      Results show that implantation of low numbers of NB cells directly into the
      adrenal gland of nude mice resulted in rapid and homogeneous tumor growth without
      tumor morbidity. Nude mice were shown to rapidly develop highly vascularized
      adrenal tumors that selectively metastasized to the liver and bone marrow. In
      addition, the newly formed mouse vessels in orthotopic but not in heterotopic
      tumors, were found to express the highly angiogenic alphavbeta3 integrin marker,
      indicating the development of a truly malignant neovasculature in orthotopic
      conditions only. This observation confirms the impact of the regional
      microenvironment on tumor biology and suggests the existence of cross-talk with
      the tumor cells. In conclusion, such model faithfully reproduces the growth,
      vascular and metastatic patterns as observed in patients. It therefore represents
      a powerful and biologically relevant tool to improve our understanding of the
      biology of NB and to develop and assess new antiangiogenic and metastasis
      targeted therapies.

PMID- 15514942
TI  - Overexpression of human pituitary tumor transforming gene (hPTTG), is regulated
      by beta-catenin /TCF pathway in human esophageal squamous cell carcinoma.
AB  - Overexpression of human pituitary tumor transforming gene (PTTG) is wildly
      detected in many tumors, including esophageal cancer. Besides overexpression of
      PTTG in esophageal squamous cell carcinoma (ESCC) tissues and cells, we detected
      accumulation of cytoplasmic beta-catenin in ESCC. In our study, a putative TCF4
      binding element (TBE) was identified in PTTG promoter region. The activity of
      PTTG promoter containing the TBE was activated by S37Abeta-catenin and inhibited
      by dominant-negative TCF. Furthermore, the activation by S37Abeta-catenin was
      mostly abrogated among PTTG promoter region without the TBE or with a mutant one.
      By using biotin-streptavidin pull-down assay, we also found that the TBE among
      PTTG promoter bound to TCF-4 protein. Moreover, levels of PTTG mRNA and protein
      were increased by S37Abeta-catenin. Finally, it is noticeable that we detected a
      correlation between beta-catenin localization and PTTG expression in 69 primary
      ESCC (p<0.01). In brief, our study shows that overexpression of PTTG in ESCC is
      likely due to the activation of beta-catenin/WNT signaling. As a target gene of
      beta-catenin/TCF pathway, PTTG may play an important role in tumorigenesis of
      human ESCC.

PMID- 15514943
TI  - Birth size and subsequent risk for prostate cancer: a prospective population
      based study in Norway.
AB  - Studies on birth size characteristics and adult risk for prostate cancer have
      been few and inconclusive. We prospectively examined the association between
      birth size and risk for prostate cancer with particular emphasis on metastatic
      disease. A total of 19,681 singleton males born between 1920 and 1958, whose
      birth records were kept at St. Olav's University Hospital (Trondheim, Norway),
      were followed up for prostate cancer by linkage to the Norwegian Cancer Registry.
      A total of 159 cases of prostate cancer were diagnosed during follow-up; 33 had
      metastases at diagnosis. Overall, there was little evidence for any association
      between birth size and prostate cancer risk; however, there was a positive
      association for birth size and metastatic disease. Men in the highest quartile of
      birth length (> or =53 cm) had a relative risk of 2.5 (95% CI 1.0-6.3) compared
      to men in the lowest quartile (<51 cm). Further, men in the highest quartile of
      both birth weight and birth length had a relative risk of 3.8 (95% CI 1.2-12.0)
      for metastatic prostate cancer compared to men in the lowest category of both
      factors. These results support the hypothesis that factors that determine
      intrauterine growth could be important for aggressive forms of prostate cancer in
      adulthood.

PMID- 15514945
TI  - Identification of human papillomaviruses in tumors of the oral cavity in an
      Indian community.
AB  - Oral cancers and other squamous cell cancers of the head and neck are common
      cancers in India, primarily due to tobacco chewing/smoking and alcohol
      consumption. Recent reports indicate involvement of human papillomavirus (HPV),
      HPV 16, in a subset of squamous cell carcinoma of head and neck (SCCHN) cases. To
      investigate the types of HPVs present in 83 oral cancers and 19 other head and
      neck tumors, degenerate primers directed to consensus regions in the HPV L1 open
      reading frame (ORF) were employed to amplify genomic DNA from tumor and when
      available, the adjacent normal mucosa. PCR-amplified products were cloned and
      sequenced. Similar studies were done on exfoliated buccal cells of 102
      individuals visiting a dental hospital for dental complaints. HPV was detected in
      32 out of 102 patients (31%), in either the tumor or the adjacent normal mucosa,
      while 5% (5/102) of the comparative group were found to be HPV-positive. Sequence
      analysis revealed a number of cutaneous HPVs, predominantly HPV types of the
      genus Beta-Papillomavirus, in the oral cavity. Multiple HPV infections were also
      commonly observed in patients (14/102; 14%). HPV 16 and 18 were each detected in
      6 patients (6/102; 6%). Neither high-risk HPVs nor multiple infections were
      observed in the mouthwash samples of the comparative group. We report that the
      oral cavity harbors a variety of different HPVs. These viruses, in conjunction
      with the carcinogens present in tobacco could contribute to carcinogenesis.

PMID- 15514944
TI  - Constitutive activation of transcription factor AP-1 in cervical cancer and
      suppression of human papillomavirus (HPV) transcription and AP-1 activity in HeLa
      cells by curcumin.
AB  - The transcription factor AP-1 plays a central role in the transcriptional
      regulation of specific types of high-risk human papillomaviruses (HPVs) such as
      HPV16 and HPV18, which are etiologically associated with the development of
      cancer of the uterine cervix in women. In our study, we investigated the AP-1
      binding activity and the expression pattern of different members of the AP-1
      transcription factor family (c-Jun, JunB, JunD, c-Fos, FosB, Fra-1 and Fra-2) in
      different grades of cervical lesions starting from mild dysplasia to invasive
      cervical tumors, including normal control tissues, using specific antibodies
      raised against each of the AP-1 members. Results indicate that though AP-1 showed
      high binding activity and the majority of its members were highly expressed in
      tumor tissues, there is a distinct pattern of gradual increase of c-fos and a
      concomitant decrease of fra-1 expression that perfectly match the progression of
      cervical lesions. While c-fos is highly expressed in invasive cervical tumor, the
      expression of fra-1 becomes almost nil or absent, but the reverse is true in both
      controls and early precancerous lesions. These findings corroborate the results
      obtained in the cervical cancer cell line, HeLa. Interestingly, despite very low
      or absent AP-1 binding in normal as well as in premalignant lesions, AP-1
      transcription and its binding activity was found to be very high in malignant
      tissues showing a preferential heterodimerization of c-fos with JunB instead of
      its canonical dimerization partner c-jun. Both in vivo and in vitro studies
      demonstrate that the overexpression of c-fos and downregulation of fra-1
      expression as well as a change in the dimerization pattern of the AP-1 complex
      seem to play a crucial role during progression to malignancy. In a previous
      study, we demonstrated that a synthetic antioxidant, pyrrolidine dithiocarbamate
      (PDTC) can selectively downregulate HPV expression in human keratinocytes and
      cervical cancer cell lines. Since a redox regulatory pathway is involved in the
      expression of HPV that can be modulated by an antioxidant-induced reconstitution
      of the AP-1 transcription complex, we have used curcumin (diferuloylmethane), an
      active component of the perennial herb turmeric, which is a potent antioxidant
      and is well-known for its antiinflammatory and anticarcinogenic activity, to
      modulate the transcription of AP-1 and HPV. We demonstrate for the first time
      that curcumin can selectively downregulate HPV18 transcription as well as the AP
      1 binding activity in HeLa cells. Most interestingly, curcumin can reverse the
      expression dynamics of c-fos and fra-1 in this tumorigenic cell line, mimicking
      the expression pattern observed in normal controls or precancerous lesions.
      Observation of curcumin-mediated complete downregulation of AP-1 binding activity
      and reversal of c-fos/fra-1 transcription to a normal state in tumorigenic HeLa
      cells represents a novel mechanism that can control transcription of pathogenic
      HPVs during keratinocyte differentiation and progression of cervical cancer. Our
      study thus provides a basis for developing a novel therapeutic approach to
      control pathogenic HPV infection by using potent antioxidative agents, such as
      curcumin.

PMID- 15514946
TI  - GRP78 expression correlates with histologic differentiation and favorable
      prognosis in neuroblastic tumors.
AB  - Glucose-regulated protein 78 (GRP78), an endoplasmic reticulum protein, is
      essential for the differentiation of neuroblastoma cells and is selectively
      induced when the cells are undergoing apoptosis. These findings suggest that
      GRP78 may affect the tumor behavior of neuroblastoma. Our study evaluates the
      association of clinicopathologic factors and patient survival with the expression
      of GRP78 in patients with neuroblastoma. GRP78 expression in 68 neuroblastic
      tumors was investigated semiquantitatively by immunohistochemistry. GRP78 mRNA
      and protein levels in 7 tumor tissues were also quantified by real-time PCR and
      Western blot respectively and correlated well with the immunohistochemical
      results. Forty (58.8%) of the 68 neuroblastic tumors showed positive GRP78
      expression. The percentage of positive GRP78 immunostaining increased as the
      tumor histology became differentiated (p = 0.001). Furthermore, positive GRP78
      expression strongly correlated with early clinical stages (P = 0.002) but
      inversely correlated with MYCN amplification (p = 0.001). Kaplan-Meier analysis
      showed that patients with positive GRP78 expression did have better survival than
      those with negative expression (5-year survival rate, 72.9% and 23.4%
      respectively, p < 0.001). Multivariate analysis further showed that GRP78
      expression was an independent prognostic factor. Moreover, GRP78 expression
      predicted better survival in patients with either undifferentiated or
      differentiated histologies. GRP78 expression still had significant prognostic
      value when the analysis was restricted to tumors of advanced stages or without
      MYCN amplification. Thus, GRP78 can serve as a novel independent favorable
      prognostic factor for patients with neuroblastoma.

PMID- 15514954
TI  - Formation of hydroxyapatite/biopolymer biomaterials. I. Microporous composites
      from solidified emulsions.
AB  - Microporous materials of controlled pore size were prepared by means of a three
      step process involving in situ hydrochemical preparation of a hydroxyapatite
      sodium caseinate (HAp-Cas) composite material into a Cas-stabilized oil-in-water
      emulsion, subsequent concentration and drying of the composite-emulsion, and
      removal of the oil by means of supercritical carbon dioxide extraction. The
      resulting composite materials were found to contain micron-sized pores in the
      space previously occupied by the oil droplets. In order to elucidate the
      structure of the resulting porous product, its Cas-HAp composition was studied in
      the corresponding nonporous composite material. In nonporous samples, a protein
      assay by means of visible spectroscopy suggested equilibrium between the Cas that
      was trapped in the composite structure and the Cas that remained in solution
      after precipitation. This observation was confirmed by separate thermogravimetric
      analysis and Fourier transform IR spectroscopy measurements.

PMID- 15514955
TI  - Risk factors for cholelithiasis in pregnancy.
AB  - This study was designed to examine the relationships of demographics,
      anthropometrics, prenatal physical activity, serum cholesterol, and nutrient
      intakes to symptomatic cholelithiasis (gallstone) occurrence in 128 northern
      plains pregnant women. Data collected at 14 and 26 weeks of pregnancy and 4 weeks
      after delivery, indicated 25.8% of the Native American and 8.3% of the Caucasian
      pregnant women experienced symptoms of cholelithiasis. Body mass indices (BMIs)
      were significantly higher in the pregnant women who experienced cholelithiasis
      than in those who did not have cholelithiasis, and prenatal physical activity was
      significantly lower in those same women. History of gallbladder disease
      (beta=.73; p=.001), BMI (beta=.33; p=.01), and prenatal physical activity (beta=
      .20; p=.04) were predictive of increased occurrence of cholelithiasis during
      pregnancy.

PMID- 15514956
TI  - The temperament of pre-term, low birth weight infants and its potential
      biological substrates.
AB  - Temperament profiles of pre-term, low birth weight (LBW) infants were assessed at
      6 months of age using standardized norms from the Revised Infant Temperament
      Questionnaire (RITQ). The contributions of perinatal risk, ethnicity, and gender
      to various temperament dimensions were examined. The sample included 152 infants
      with a mean birth weight of 1687 g and a mean gestational age of 31 weeks. Eighty
      percent of the infants were classified as having temperaments that were difficult
      to manage. Irregularity of the infants' biorhythms, slowness in their ability to
      adapt to changes, and distractibility were the most problematic. Birth weight,
      gestational age, and gender were not associated with temperament. Perinatal
      morbidity was related to the temperament dimension of infant persistence, with
      implications for the infant's attention span and task performance. Euro American
      infants were rated as more persistent and less intense in emotional expression
      than were infants of other ethnic groups. Results suggest the need for a more
      direct assessment of the effects of neurobiological processes on development of
      temperament phenotypes and for measurement of temperament that is socioculturally
      appropriate.

PMID- 15514957
TI  - The reliability and validity of the Chinese version of the Trait Anxiety Scale
      for Children.
AB  - The availability of a valid and reliable tool that accurately measures and
      differentiates pre-operative anxiety level of children is crucial before any
      intervention can be appropriately planned, provided, and evaluated. The purposes
      of this study were to translate the original Trait Anxiety Scale for Children
      into Chinese and evaluate the psychometric properties of the newly translated
      scale for its utility in clinical practice and research. Five hundred and
      nineteen children from a primary school were recruited for this study. The
      instrument demonstrated adequate internal consistency reliability, and strong
      evidence of content and construct validity. Factor analysis confirmed the
      construct validity of the scale with a good fit between the factor structure of
      the scale and the observed data. Results suggest that the Chinese version of the
      Trait Anxiety Scale for Children can be used as a self-report assessment tool in
      measuring trait anxiety level of Chinese children ages 7-12 years.

PMID- 15514958
TI  - Coordination in nurses' listening activities and communication about patient
      nurse relationships.
AB  - The purpose of this analysis was to examine whether nurses' listening behavior,
      especially the coordination of their nonverbal involvement activities with those
      of their patients, communicates information about patient-nurse relationships.
      Participants were 126 college women who responded to a 30-item instrument
      measuring relational information that was communicated to them by nurses'
      behavior in videotaped segments of interactions between a patient/actress and 12
      nurses. Participants' responses to two consecutive interaction segments were
      selected for this analysis. The research team coded the patient's and nurses'
      listening activities, and they calculated coordination and activity rates for all
      interaction segments. Multiple regression analysis revealed that nurses' verbal
      listening activities, such as reflection, their nonverbal involvement activities,
      and their simultaneous coordination of nonverbal involvement activities with
      those of the patient predicted relational information dimensions of
      trust/receptivity, depth/similarity/affection, composure, and non-formality.
      Thus, nurses' listening behavior, including coordination, may contribute to
      communication about patient-nurse relationships.

PMID- 15514960
TI  - Intrauterine growth retardation in full-term newborn infants with birth weights
      greater than 2,500 g.
AB  - Intrauterine growth retardation (IUGR) is an overlooked problem in full-term
      infants with birth weights greater than 2,500 g. Birth weight less than the 10th
      percentile underestimates the presence of IUGR. The purpose of this study was to
      determine the prevalence of IUGR in full-term infants and to identify
      sociodemographic and maternal characteristics associated with IUGR. The Ohio
      Department of Health Vital Statistics database was used to obtain data related to
      sociodemographic and maternal characteristics. The fetal growth ratio (FGR) was
      used to determine the presence of IUGR. The sample consisted of 1,569 infants
      with normal ratios and 1,364 infants classified as IUGR. Infants with IUGR were
      more often male and African American or Asian American. Maternal characteristics
      associated with IUGR included history of smoking during pregnancy, lower pre
      pregnancy weight, lower weight gain during pregnancy, and inadequate prenatal
      care. IUGR is present in a significant number of full-term infants with birth
      weights greater than 2,500 g. The long-term effects of IUGR in these infants
      remain to be determined.

PMID- 15514961
TI  - Behavior problems in young children: an analysis of cross-informant agreements
      and disagreements.
AB  - This study examined (a) convergence between parents' and day care teachers'
      ratings of children's behavior problems, and (b) whether agreements and
      disagreements were associated with characteristics of the informant, context, or
      measures. Parents of 241, 2-4-year old children in day care centers serving low
      income families completed measures of child behavior problems, parenting style,
      stress, depression, and self-efficacy. Teachers completed a measure of classroom
      behavior problems. There was a low correlation between parents' and teachers'
      ratings of child behavior (r=.17), and few children (2.5%) received high behavior
      problem scores from both parents and teachers. Cross-informant agreement on high
      behavior problem children was related to characteristics of the informants and
      home context. Implications for identifying children at risk are discussed.

PMID- 15514962
TI  - Physical activity, self-efficacy, and perceived exertion among adolescents.
AB  - The relationship of self-efficacy, a sense of confidence in personal physical
      activity (PA) skills, to perceived exertion during activity was explored among
      168 African American and European American boys and girls between 9 and 17 years
      of age. Participants walked/ran on a treadmill at a speed equivalent to 60% of
      their peak VO2 for 20 minutes and provided ratings of exertion every 4 minutes.
      Pre-activity self-efficacy predicted perceived exertion for boys only. Girls were
      lower than boys in pre-activity self-efficacy and subsequently reported greater
      perceived exertion. For both genders, lower perceived exertion during PA resulted
      in higher post-activity self-efficacy. Uncomfortable perceptions of exertion
      during initial efforts to increase PA are likely to discourage future activity.
      Interventions that can lower perceptions of exertion may enhance self-efficacy
      and promote a sense of competence in PA skills.

PMID- 15514963
TI  - Audio-visual relaxation training for anxiety, sleep, and relaxation among Chinese
      adults with cardiac disease.
AB  - The long-term effect of an audio-visual relaxation training (RT) treatment
      involving deep breathing, exercise, muscle relaxation, guided imagery, and
      meditation was compared with routine nursing care for reducing anxiety, improving
      sleep, and promoting relaxation in Chinese adults with cardiac disease. This
      research was a quasi-experimental, two-group, pretest-posttest study. A
      convenience sample of 100 cardiology patients (41 treatment, 59 control) admitted
      to one large medical center hospital in the Republic of China (ROC) was studied
      for 1 year. The hypothesized relationships were supported. RT significantly (p
      <.05) improved anxiety, sleep, and relaxation in the treatment group as compared
      to the control group. It appears audio-visual RT might be a beneficial adjunctive
      therapy for adult cardiac patients. However, considerable further work using
      stronger research designs is needed to determine the most appropriate
      instructional methods and the factors that contribute to long-term consistent
      practice of RT with Chinese populations.

PMID- 15514964
TI  - Effects of subtoxic concentrations of benzoyl peroxide on cell lipid metabolism.
AB  - Benzoyl peroxide (BP), a tumor promoter, has been shown to cause free-radical
      induced lipid peroxidation and membrane damage at toxic concentrations. However,
      its effects on lipid metabolism at concentrations that were not overtly toxic
      have not been investigated. The purpose of the current study was to examine the
      effects of BP and its final degradation product, benzoic acid (BA), on lipid
      metabolism. Two cell lines, hamster cheek pouch (HCP) and human monocytes (THP
      1), were used to determine the effects of BP, BA, and BP combined with FeCl2 on
      cell lipid metabolism. Cells were exposed to BP and 14C acetate for 24 h, or
      cells with prelabeled lipids were harvested, and the lipids were extracted and
      separated with the use of thin-layer chromatography. Lipid metabolism of some
      neutral lipids such as triglycerides was altered for both cell types in response
      to BP. Also, cholesterol content was reduced in THP-1 cells and a phospholipid,
      phosphatidylethanolamine (PE), was reduced in HCP cells. The final degradation
      product of BP, BA, failed to elicit any response in lipid metabolism. Subtoxic
      concentrations of BP induced changes in neutral lipids such as triglycerides and
      cholesterol. The metabolism of major phospholipids except PE remained unchanged.
      The effects were related to BP and its degradation and varied with the cell type.

PMID- 15514965
TI  - Long-term persistence of clonally expanded T cells in patients with polymyositis.
AB  - Polymyositis is a CD8(+) T-cell-mediated disease. T-cell clonal expansions are
      observed at disease onset, but little is known about their persistence over time.
      Qualitative and quantitative spectratyping demonstrated that PM relapse features
      dramatically perturbed blood T-cell repertoires but is not associated with the
      emergence of new T-cell clones. It is striking that patients in remission also
      maintained all their T-cell repertoire abnormalities. The clonally expanded T
      cells displayed a memory phenotype, expressed intracellular perforin, and
      dramatically responded to IL-2, showing a potential to be reactivated upon
      appropriate conditions. These results indicate that persistent T-cell clonal
      expansion is an important feature of polymyositis.

PMID- 15514966
TI  - Release of nucleophosmin from the nucleus: Involvement in aloe-emodin-induced
      human lung non small carcinoma cell apoptosis.
AB  - Aloe-emodin (1,8-dihydroxy-3-(hydroxymethyl)-anthraquinone) is one of the active
      constituents from the root and rhizome of Rheum palmatum. Our previous study has
      demonstrated that aloe-emodin induced a significant change in the expression of
      lung cancer cell apoptosis-related proteins compared to those of control cells.
      However, the molecular mechanisms underlying the biological effects of aloe
      emodin still remain unknown. Based on these reasons, we were interested in the
      change of aloe-emodin-induced total protein expression by the proteomics
      technique during aloe-emodin-induced lung cancer cell apoptosis. Our study
      applied 2D electrophoresis to analyze the proteins involved in aloe-emodin
      induced apoptosis in H460 cells. We found that the release of nucleophosmin from
      the nucleus to the cytosol and the degradation of nucleophosmin were associated
      with aloe-emodin-induced H460 cell apoptosis. Our study also demonstrated that
      the gene expression of nucleophosmin remained unchanged after treatment with aloe
      emodin. The aloe-emodin-caused increase in the amount of proform and fragment of
      nucleophosmin in cytoplasm may be one of the important events for aloe-emodin
      induced H460 cell apoptosis.

PMID- 15514967
TI  - Do dietary lycopene and other carotenoids protect against prostate cancer?
AB  - To determine whether dietary intake of lycopene and other carotenoids has an
      etiological association with prostate cancer, a case-control study was conducted
      in Hangzhou, southeast China during 2001-2002. The cases were 130 incident
      patients with histologically confirmed adenocarcinoma of the prostate. The
      controls were 274 hospital inpatients without prostate cancer or any other
      malignant diseases. Information on usual food consumption, including vegetables
      and fruits, was collected by face-to-face interviews using a structured food
      frequency questionnaire. The risks of prostate cancer for the intake of
      carotenoids and selected vegetables and fruits rich in carotenoids were assessed
      using multivariate logistic regression, adjusting for age, locality, education,
      income, body mass index, marital status, number of children, family history of
      prostate cancer, tea drinking, total fat and caloric intake. The prostate cancer
      risk declined with increasing consumption of lycopene, alpha-carotene, beta
      carotene, beta-cryptoxanthin, lutein and zeaxanthin. Intake of tomatoes, pumpkin,
      spinach, watermelon and citrus fruits were also inversely associated with the
      prostate cancer risk. The adjusted odds ratios for the highest versus the lowest
      quartiles of intake were 0.18 (95% CI: 0.08-0.41) for lycopene, 0.43 (95% CI:
      0.21-0.85) for alpha-carotene, 0.34 (95% CI: 0.17-0.69) for beta-carotene, 0.15
      (95% CI: 0.06-0.34) for beta-cryptoxanthin and 0.02 (95% CI: 0.01-0.10) for
      lutein and zeaxanthin. The corresponding dose-response relationships were also
      significant, suggesting that vegetables and fruits rich in lycopene and other
      carotenoids may be protective against prostate cancer.

PMID- 15514968
TI  - In vitro EBV-infected subline of KMH2, derived from Hodgkin lymphoma, expresses
      only EBNA-1, while CD40 ligand and IL-4 induce LMP-1 but not EBNA-2.
AB  - In about 50% of classical Hodgkin lymphomas, the Hodgkin/Reed Sternberg (H/RS)
      cells carry Epstein-Barr virus (EBV). The viral gene expression in these cells is
      restricted to EBNA-1, EBERs, LMP-1 and LMP-2 (type II latency). The origin of
      H/RS cells was defined as crippled germinal center B cells that escaped
      apoptosis. In spite of numerous attempts, only few typical Hodgkin lymphoma (HL)
      lines have been established. This suggests that the cells require survival
      factors that they receive in the in vivo microenvironment. If EBV is expected to
      drive the cells for growth in culture, the absence of EBNA-2 may explain the
      incapacity of H/RS cells for in vitro proliferation. In EBV carrying B
      lymphocytes, functional EBNA-2 and LMP-1 proteins are required for in vitro
      growth. For analysis of the interaction between EBV and the H/RS cells, we
      infected the CD21-positive HL line KMH2 with the B958 and Akata viral strains.
      Only EBNA-1 expression was detected in a few cells in spite of the fact that all
      cells could be infected. Using a neomycin-resistance-tagged recombinant EBV
      strain (Akata-Neo) we established an EBV-positive subline that was carried on
      selective medium. In contrast to the type II EBV expression pattern of H/RS cells
      in vivo, the KMH2 EBV cells did not express LMP-1. The EBV expression pattern
      could be modified in this type I subline. LMP-1 could be induced by the histone
      deacetylase inhibitors TSA and n-butyrate, by 5-AzaC, a demethylating agent, and
      by phorbol ester. None of these treatments induced EBNA-2. Importantly, exposure
      to CD40 ligand and IL-4 induced LMP-1 without EBNA-2 expression and lytic
      replication. The KMH2 EBV cells expressed LMP-2A, but not LMP-2B mRNAs. This
      result is highly relevant for the type II expression pattern of H/RS cells in
      vivo, since these stimuli can be provided by the surrounding activated T
      lymphocytes.

PMID- 15514969
TI  - Women with polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and
      methionine synthase (MS) are less likely to have cervical intraepithelial
      neoplasia (CIN) 2 or 3.
AB  - The role of nutrient-related genetic susceptibility factors for pre-cancerous
      lesions is gaining attention. We conducted a study to examine associations
      between polymorphisms in folate pathway coenzymes (methylenetetrahydrofolate
      reductase [MTHFR] and methionine synthase [MS]) and cervical intraepithelial
      neoplasia (CIN) 2 or 3 in a population exposed to folic acid by the food
      fortification program in the United States. Status of MTHFR and MS and
      circulating concentrations of folate, vitamins B12, A, E, C and total carotene
      were ascertained in 170 Caucasian and 266 African-American women positive for
      high-risk human papilloma virus (HR-HPV). Polymorphism status was determined
      using polymerase chain reaction assays. Micronutrient concentrations were
      measured using radiobinding assays, high performance liquid chromatography or
      spectrophotometry. Presence/absence of CIN 2 or 3 was determined on the basis of
      histology results and the association with risk factors was examined using
      multivariable analyses. Eighty women had CIN 2 or 3 lesions and they were
      compared to 356 women who had CIN 1, ASCUS or normal cytology. We found that
      women polymorphic for MTHFR were less likely to have CIN 2 or 3 (odds ratio [OR]
      = 0.43, 95% confidence interval [CI] = 0.23-0.79). No associations were seen with
      MS polymorphism alone (OR = 0.72, 95% CI = 0.43-1.21); however, women polymorphic
      for both MTHFR and MS were less likely to have CIN 2 or 3 (OR = 0.21, 95% CI =
      0.08-0.62). We conclude that these polymorphisms in the folate metabolic pathway
      were associated with a lower likelihood of CIN 2 or 3 in a population exposed to
      adequate amounts of folate from exposure to food fortification with folic acid.

PMID- 15514970
TI  - Differential expression of cell adhesion genes: implications for drug resistance.
AB  - It is well known that tumors arising from tissues such as kidney, pancreas, liver
      and stomach are particularly refractory to treatment. Searching for new
      anticancer drugs using cells in culture has yielded some effective therapies, but
      these refractory tumors remain intractable. Studies that compare cells grown in
      suspension to similar cells grown attached to one another as aggregates have
      suggested that it is adhesion to the extracellular matrix of the basal membrane
      that confers resistance to apoptosis and, hence, resistance to cytotoxins. The
      genes whose expression correlates with poor survival might, therefore, act
      through such a matrix-to-cell suppression of apoptosis. Indeed, correlative
      mining of gene expression and patient survival databases suggests that poor
      survival in patients with metastatic cancer correlates highly with tumor
      expression of a common theme: the genes involved in cell adhesion and the
      cytoskeleton. If the proteins involved in tethering cells to the extracellular
      matrix are important in conferring drug resistance, it may be possible to improve
      chemotherapy by designing drugs that target these proteins.

PMID- 15514971
TI  - IL-1beta induces stabilization of IL-8 mRNA in malignant breast cancer cells via
      the 3' untranslated region: Involvement of divergent RNA-binding factors HuR,
      KSRP and TIAR.
AB  - IL-8 plays an integral role in promoting the malignant phenotype in breast
      cancer, and its production is directly influenced by inflammatory cytokines in
      the tumor microenvironment. Here, we show that activation of IL-1beta receptors
      on malignant HS578t and MDA-MB-231 breast cancer cells strongly induces IL-8
      expression and that RNA stabilization is persistently activated at least 12-24 hr
      after stimulation. SB 203580 and rapamycin reversed the RNA stabilization effect
      of IL-1beta in a dose-dependent manner, suggesting involvement of the p38/MAP
      kinase and mTOR pathways. A luciferase reporter assay indicated that the
      stabilization effect was dependent on cis elements in the 3'-untranslated region
      (UTR) of the IL-8 transcript. By UV cross-linking, we identified multiple
      cellular factors that interact with the IL-8 3'UTR, ranging 34-76 kDa.
      Immunoprecipitation analysis indicated that HuR, KSRP and TIAR bound to one or
      more loci in the 3'UTR. While the cross-linking patterns were similar,
      quantitative immunoprecipitation of native IL-8 RNA from IL-1beta-stimulated
      cytoplasmic extract revealed a 20-fold greater association of transcript with the
      stabilizing factor HuR vs. the destabilizing factor KSRP. In conclusion, IL-1beta
      is a potent cytokine stimulus for IL-8 RNA stabilization in breast cancer cells,
      possibly by enhanced binding of cytoplasmic HuR to the 3'UTR.

PMID- 15514972
TI  - Radiological and pulmonary function outcomes of children with SARS.
AB  - We examined the radiological and pulmonary function outcomes of children affected
      with severe acute respiratory syndrome (SARS) at 6 months from diagnosis. Twenty
      one female and 26 male Chinese patients (median age, 13.6 years; interquartile
      range, 9.9-16.0) were studied. In each subject, high-resolution computed
      tomography (HRCT) of the thorax and pulmonary function were assessed. All
      children were asymptomatic and had a normal clinical examination. Mild pulmonary
      abnormalities were detected on HRCT in 16 (34.0%) subjects, including residual
      ground-glass opacification (n = 5), air trapping (n = 8), and a combination of
      ground-glass changes and air trapping (n = 3). The need for oxygen
      supplementation (P = 0.02) and lymphopenia during the course of illness (P =
      0.012) were significant risk factors in predicting abnormal HRCT. There were no
      significant lung function differences between those with and without HRCT
      abnormalities. Despite complete clinical resolution, a considerable proportion of
      children affected with SARS had abnormal HRCT findings at 6 months. These
      abnormalities were more prevalent in those with severe disease. It is important
      that careful follow-up be carried out to assess the clinical significance and
      persistence of such abnormalities.

PMID- 15514973
TI  - Preoperative pulmonary hemodynamics determines changes in airway and tissue
      mechanics following surgical repair of congenital heart diseases.
AB  - To characterize the effect of changes in pulmonary hemodynamics on airway and
      tissue mechanics, forced oscillatory input impedance of the respiratory system
      (Zrs) was measured between 0.4-12 Hz in two groups of children undergoing
      surgical repair of congenital heart disease (CHD) immediately before sternotomy
      and after chest closure during short apneic intervals. Children with lesions
      associated with high pulmonary blood flow and/or pressure (septal defects; HP
      group, n = 12) and children with hypoperfused lungs (tetralogy of Fallot; LP
      group, n = 12) were included in the study. Airway resistance (Raw), and
      coefficients of respiratory tissue damping (G) and elastance (H), were estimated
      from Zrs by model-fitting. A postoperative reduction in pulmonary blood flow
      and/or pressure in the HP group resulted in an immediate decrease in Raw of 29 +/
      9 (SE)% (P < 0.05), whereas children in the LP group had increases in Raw (24 +/
      17%, no significance) after surgery. No significant change was observed in G in
      either the HP (6.4 +/- 13%) or LP (27 +/- 23%) group, while H increased in
      children of both the HP (23 +/- 8%, P < 0.05) and LP (36 +/- 7%, P < 0.01)
      groups. These results suggest that the preoperative pulmonary hemodynamic
      condition determines changes in airway mechanics: surgical repair of CHD leads to
      an improvement in airway function only in children with congested lungs. The
      adverse effects of surgery, mechanical ventilation, and/or cardiopulmonary bypass
      may be responsible for the increased stiffness of the respiratory system observed
      in both groups of children.

PMID- 15514975
TI  - Retrieving meaning after temporal lobe infarction: the role of the basal language
      area.
AB  - During speech comprehension the auditory association cortex in the superior
      temporal cortex is involved in perceptual analysis of the speech signal, whereas
      the basal language area in the inferior temporal cortex mediates access to word
      meaning. Disruption of the interaction between the superior and inferior temporal
      cortices is one factor that may determine recovery from aphasic stroke. We used
      positron emission tomography to investigate semantic processing within inferior
      temporal cortex in control subjects and after infarction involving the superior
      temporal cortex. In the control group, semantic decision making on clear speech
      activated both anterior fusiform gyri. Chronic aphasic patients were impaired at
      the task and demonstrated reduced activation within the left anterior fusiform
      gyrus. A similar pattern of impaired performance and reduced left anterior
      fusiform gyrus activation was observed when control subjects heard perceptually
      degraded speech. Performance in both groups predicted activity in the right
      anterior fusiform gyrus and the temporal poles, where accuracy linearly
      correlated with activity. These results demonstrate that the function of the
      basal language area is sensitive to changes in the quality of perceptual input.
      In addition, different profiles of response observed in each hemisphere suggest
      distinct contributions of both left and right inferior temporal cortices to the
      semantic processing of speech.

PMID- 15514976
TI  - Increased D1 dopamine receptor signaling in levodopa-induced dyskinesia.
AB  - Involuntary movements, or dyskinesia, represent a debilitating complication of
      levodopa therapy for Parkinson's disease. Although changes affecting D(1) and
      D(2) dopamine receptors have been studied in association with this condition, no
      causal relationship has yet been established. Taking advantage of a monkey brain
      bank constituted to study levodopa-induced dyskinesia, we report changes
      affecting D(1) and D(2) dopamine receptors within the striatum of normal,
      parkinsonian, nondyskinetic levodopa-treated parkinsonian, and dyskinetic
      levodopa-treated parkinsonian animals. Whereas D(1) receptor expression itself is
      not related to dyskinesia, D(1) sensitivity per D(1) receptor measured by D(1)
      agonist-induced [(35)S]GTPgammaS binding is linearly related to dyskinesia.
      Moreover, the striata of dyskinetic animals show higher levels of cyclin
      dependent kinase 5 (Cdk5) and of the dopamine- and cAMP-regulated phosphoprotein
      of 32kDa (DARPP-32). Our data suggest that levodopa-induced dyskinesia results
      from increased dopamine D(1) receptor-mediated transmission at the level of the
      direct pathway.

PMID- 15514977
TI  - Characterization of GalR1, GalR2, and GalR3 immunoreactivity in catecholaminergic
      nuclei of the mouse brain.
AB  - The distribution of immunoreactivity for the three identified neuropeptide
      galanin receptors, GalR1, GalR2, and GalR3, was determined in areas of the mouse
      brain involved in drug addiction, including the ventral tegmental area (VTA),
      substantia nigra (SN), nucleus accumbens (NA), and locus coeruleus (LC). All
      three galanin receptors are found in the VTA, SN, NA, and LC; however, GalR1
      protein is most highly represented in the VTA, NA, and SN, suggesting that GalR1
      may play a predominant role in galanin-mediated regulation of dopamine
      neurotransmission. GalR1 and GalR3 protein levels are high in the LC, suggesting
      that these isoforms may be important for galanin-mediated regulation of
      noradrenergic transmission during opiate withdrawal. Although the distribution of
      GalR1, GalR2, and GalR3 largely recapitulates the pattern of galanin binding
      throughout the brain, some discrepancies exist, suggesting that another galanin
      receptor(s) may be present in some brain areas. Overall, GalR1, GalR2, and GalR3
      are distributed widely throughout the brain, correlate with widespread galanin
      binding, and colocalize with tyrosine hydroxylase in catecholaminergic brain
      areas.

PMID- 15514978
TI  - Differentiation of the dopaminergic phenotype in the olfactory system of neonatal
      and adult mice.
AB  - Olfactory bulb (OB) interneurons are derived primarily postnatally from
      progenitors in the anterior subventricular zone (SVZa) and migrate to the OB in
      the rostral migratory stream (RMS). Progenitors differentiate into phenotypically
      diverse granule and periglomerular cells by as yet undefined mechanisms. To
      visualize spatiotemporal aspects of periglomerular dopamine (DA) neuron
      differentiation, two independently derived transgenic mouse lines were analyzed
      with a 9-kb tyrosine hydroxylase (TH) promoter to drive either a LacZ or an
      enhanced green fluorescent protein (EGFP) reporter gene. Both reporters showed
      similar neonatal expression that varied from low levels in RMS, to moderate in
      the superficial granule cell layer, to strong in relatively large cells, possibly
      external tufted cells, in the periglomerular region. TH mRNA and protein were not
      detected in the RMS but were colocalized with the transgenes in neonatal
      superficial granule and periglomerular cells. By comparison, TH protein in adults
      was further limited to periglomerular cells. To demonstrate that transcriptional
      regulation was the same for EGFP and TH, expression was shown to decline
      similarly in the OB ipsilateral to odor deprivation produced by adult unilateral
      naris closure. Of two genes previously hypothesized to regulate OB DA expression,
      only regulated expression of the orphan receptor Nurr1, but not the homeobox
      containing genes Dlx-1 and -2, was consistent with a role in regulation of the DA
      phenotype. These data demonstrate for the first time that DA phenotypic
      differentiation in neonates begins with low-level transcription in migrating
      progenitors in the RMS and culminates with activity-dependent protein expression
      in periglomerular cells innervated by olfactory receptor cells.

PMID- 15514979
TI  - Pax6 guides a relay of pioneer longitudinal axons in the embryonic mouse
      forebrain.
AB  - We have characterized a system of early neurons that establish the first two
      major longitudinal tracts in the embryonic mouse forebrain. Axon tracers and
      antibody labels were used to map the axon projections in the thalamus from
      embryonic days 9.0-12, revealing several distinct neuron populations that
      contributed to the first tracts. Each of the early axon populations first grew
      independently, pioneering a short segment of new tract. However, each axon
      population soon merged with other axons to form one of only two shared
      longitudinal tracts, both descending: the tract of the postoptic commissure
      (TPOC), and, in parallel, the stria medullaris. Thus, the forebrain longitudinal
      tracts are pioneered by a relay of axons, with distinct axon populations
      pioneering successive segments of these pathways. The extensive merging of tracts
      suggests that axon-axon interactions are a major guidance mechanism for
      longitudinal axons. Several axon populations express tyrosine hydroxylase,
      identifying the TPOC as a major pathway for forebrain dopaminergic projections.
      To start a genetic analysis of pioneer axon guidance, we have identified the
      transcription factor Pax6 as critical for tract formation. In Pax6 mutants, both
      longitudinal tracts failed to form due to errors by every population of early
      longitudinal axons. Taken together, these results have identified potentially
      important interactions between series of pioneer axons and the Pax6 gene as a
      general regulator of longitudinal tract formation in the forebrain.

PMID- 15514980
TI  - Acute demyelination disrupts the molecular organization of peripheral nervous
      system nodes.
AB  - Intraneurally injected lysolecithin causes both segmental and paranodal
      demyelination. In demyelinated internodes, axonal components of nodes fragment
      and disappear, glial and axonal paranodal and juxtaparanodal proteins no longer
      cluster, and axonal Kv1.1/Kv1.2 K+ channels move from the juxtaparanodal region
      to appose the remaining heminodes. In paranodal demyelination, a gap separates
      two distinct heminodes, each of which contains the molecular components of normal
      nodes; paranodal and juxtaparanodal proteins are properly localized. As in normal
      nodes, widened nodal regions contain little or no band 4.1B. Lysolecithin also
      causes "unwinding" of paranodes: The spiral of Schwann cell membrane moves away
      from the paranodes, but the glial and axonal components of septate-like junctions
      remain colocalized. Thus, acute demyelination has distinct effects on the
      molecular organization of the nodal, paranodal, and juxtaparanodal region,
      reflecting altered axon-Schwann cell interactions.

PMID- 15514981
TI  - Differential vulnerability of propriospinal tract neurons to spinal cord
      contusion injury.
AB  - The propriospinal system is important in mediating reflex control and in
      coordination during locomotion. Propriospinal neurons (PNs) present varied
      patterns of projections with ascending and/or descending fibers. Following spinal
      cord contusion injury (SCI) in the rat, certain supraspinal pathways, such as the
      corticospinal tract, appear to be completely abolished, whereas others, such as
      the rubrospinal and vestibuospinal tracts, are only partially damaged. The amount
      of damage to propriospinal axons following different severities of SCI is not
      fully known. In the present study retrograde and anterograde tracing techniques
      were used to assess the projection patterns of propriospinal neurons in order to
      determine how this system is affected following SCI. Our findings reveal that PNs
      have differential vulnerabilities to SCI. While short thoracic propriospinal
      axons are severely damaged after injury, 5-7% of long descending propriospinal
      tract (LDPT) projections survive following 50 and 12.5-mm weight drop contusion
      lesions, respectively, albeit with a reduced intensity of retrograde label. Even
      though the axons of short thoracic propriospinal cells are damaged, their cell
      bodies of origin remain intact 2 weeks after injury, indicating that they have
      not undergone postaxotomy retrograde cell death at this time point. Thus, short
      PNs may constitute a very attractive population of cells to study regenerative
      approaches, whereas LDPT neurons with spared axons could be targeted with
      therapeutic interventions, seeking to enhance recovery of function following
      incomplete lesions to the spinal cord.

PMID- 15514982
TI  - Organization of rat vibrissa motor cortex and adjacent areas according to
      cytoarchitectonics, microstimulation, and intracellular stimulation of identified
      cells.
AB  - The relationship between motor maps and cytoarchitectonic subdivisions in rat
      frontal cortex is not well understood. We use cytoarchitectonic analysis of
      microstimulation sites and intracellular stimulation of identified cells to
      develop a cell-based partitioning scheme of rat vibrissa motor cortex and
      adjacent areas. The results suggest that rat primary motor cortex (M1) is
      composed of three cytoarchitectonic areas, the agranular medial field (AGm), the
      agranular lateral field (AG1), and the cingulate area 1 (Cg1), each of which
      represents movements of different body parts. Vibrissa motor cortex corresponds
      entirely and for the most part exclusively to AGm. In area AG1 body/head
      movements can be evoked. In posterior area Cg1 periocular/eye movements and in
      anterior area Cg1 nose movements can be evoked. In all of these areas stimulation
      thresholds are very low, and together they form a complete representation of the
      rat's body surface. A strong myelinization and an expanded layer 5 characterize
      area AGm. We suggest that both the strong myelinization and the expanded layer 5
      of area AGm may represent cytoarchitectonic specializations related to control of
      high-speed whisking behavior.

PMID- 15514983
TI  - Cellular and subcellular distribution of spinophilin, a PP1 regulatory protein
      that bundles F-actin in dendritic spines.
AB  - Spinophilin is an actin binding protein that positions protein phosphatase 1 next
      to its substrates in dendritic spines. It contains a single PDZ domain and has
      the biochemical characteristics of a cytoskeletal scaffolding protein. Previous
      studies suggest that spinophilin is present in most spines, but the concentration
      of spinophilin varies from brain region to region in a manner that does not
      simply reflect differences in spine density. Here, we show that spinophilin is
      enriched in the great majority of dendritic spines in cerebral cortex,
      caudatoputamen, hippocampal formation, and cerebellum, irrespective of regional
      differences in spinophilin concentration. In addition, spinophilin is present
      postsynaptic to asymmetrical contacts on interneuronal dendritic shafts. We
      further show that, in hippocampus and ventral pallidum, spinophilin is
      occasionally present in dendritic shafts adjacent to gamma-aminobutyric acid
      containing contacts. Thus, the functional role of spinophilin may not be
      exclusively restricted to excitatory synapses and may be significant at a small
      fraction of inhibitory contacts. These data also suggest that the concentration
      of spinophilin per spine is variable and is likely regulated by local
      physiological factors and/or regional influences.

PMID- 15514984
TI  - A comprehensive picture of non-site specific oxidation of methionine residues by
      peroxides in protein pharmaceuticals.
AB  - In this article, a comprehensive picture of the oxidation of protein
      pharmaceuticals by peroxides is developed based on our earlier computational and
      experimental studies. We propose a new mechanism, the water-mediated mechanism,
      for the oxidation of methionine residues, and it has been shown to satisfy all
      available experimental data including new data reported here. Based on the water
      mediated mechanism, we found a structural property, average 2-shell water
      coordination number, that correlates well to the relative rates of oxidation of
      methionine groups. We used this to study the oxidation of granulocyte colony
      stimulating factor (G-CSF) and 1-34 human parathyroid hormone hPTH(1-34). We
      believe that this comprehensive picture should aid researchers in the
      pharmaceutical sciences to develop solvent formulations for therapeutic proteins
      in a more rational way.

PMID- 15514985
TI  - Application of ALOGPS to predict 1-octanol/water distribution coefficients, logP,
      and logD, of AstraZeneca in-house database.
AB  - The ALOGPS 2.1 was developed to predict 1-octanol/water partition coefficients,
      logP, and aqueous solubility of neutral compounds. An exclusive feature of this
      program is its ability to incorporate new user-provided data by means of self
      learning properties of Associative Neural Networks. Using this feature, it
      calculated a similar performance, RMSE = 0.7 and mean average error 0.5, for 2569
      neutral logP, and 8122 pH-dependent logD(7.4), distribution coefficients from the
      AstraZeneca "in-house" database. The high performance of the program for the
      logD(7.4) prediction looks surprising, because this property also depends on
      ionization constants pKa. Therefore, logD(7.4) is considered to be more difficult
      to predict than its neutral analog. We explain and illustrate this result and,
      moreover, discuss a possible application of the approach to calculate other
      pharmacokinetic and biological activities of chemicals important for drug
      development.

PMID- 15514986
TI  - Mechanism for benzyl alcohol-induced aggregation of recombinant human interleukin
      1 receptor antagonist in aqueous solution.
AB  - Benzyl alcohol, an antimicrobial preservative, accelerates aggregation and
      precipitation of recombinant human interleukin-1 receptor antagonist (rhIL-1ra)
      in aqueous solution. The loss of native monomer during incubation at 37 degrees C
      was determined by analysis of sample aliquots with size exclusion high
      performance liquid chromatography (SE-HPLC). Benzyl alcohol caused minor
      perturbation of the tertiary structure of the protein without changing its
      secondary structure, documenting that the preservative caused a minor shift in
      the protein molecular population toward partially unfolded species. Consistent
      with this conclusion, in the presence of benzyl alcohol the rate of H-D exchange
      was accelerated and the fluorescence of 1-anilinonaphthalene-8-sulfonic acid in
      the presence of rhIL1ra was increased. Benzyl alcohol did not alter the free
      energy of unfolding based on unfolding experiments in urea or guanidine HCl. With
      differential scanning calorimetry it was determined that benzyl alcohol reduced
      the apparent Tm of rhIL-1ra, but this effect occurred because the preservative
      lowered the temperature at which the protein aggregated during heating.
      Isothermal calorimetry documented that the interaction of benzyl alcohol with
      rhIL-1ra is relatively weak and hydrophobically driven. Thus, benzyl alcohol
      accelerates protein aggregation by binding to the protein and favoring an
      increase in the level of partially unfolded, aggregation-competent species.
      Sucrose partially inhibited benzyl alcohol-induced aggregation and tertiary
      structural change. Sucrose is preferentially excluded from the surface of the
      protein, favoring most compact native state species over expanded aggregation
      prone forms.

PMID- 15514987
TI  - Structural characterization of prazosin hydrochloride and prazosin free base.
AB  - The three-dimensional solid-state structures of prazosin hydrochloride,
      C19H22N5O4+.Cl- (A), and prazosin free base, C19H21N5O4 (B), have been determined
      by synchrotron X-ray powder diffraction. A and B crystallize in triclinic P-1 and
      monoclinic Cc space groups, respectively, with one structural unit per asymmetric
      part. In A and B, the prazosin molecule adopts different conformations, which do
      not correspond to those obtained by DFT optimizations of protonated and free
      prazosin.

PMID- 15514988
TI  - Differential expression of T-type calcium channels in P/Q-type calcium channel
      mutant mice with ataxia and absence epilepsy.
AB  - Mutations in P/Q-type calcium channels generate common phenotypes in mice and
      humans, which are characterized by ataxia, paroxysmal dyskinesia, and absence
      seizures. Subsequent functional changes of T-type calcium channels in thalamus
      are observed in P/Q-type calcium channel mutant mice and these changes play
      important roles in generation of absence seizures. However, the changes in T-type
      calcium channel function and/or expression in the cerebellum, which may be
      related to movement disorders, are still unknown. The leaner mouse exhibits
      severe ataxia, paroxysmal dyskinesia, and absence epilepsy due to a P/Q-type
      calcium channel mutation. We investigated changes in T-type calcium channel
      expression in the leaner mouse thalamus and cerebellum using quantitative real
      time polymerase chain reaction (qRT-PCR) and quantitative in situ hybridization
      histochemistry (ISHH). qRT-PCR analysis showed no change in T-type calcium
      channel alpha 1G subunit (Cav3.1) expression in the leaner thalamus, but a
      significant decrease in alpha 1G expression in the whole leaner mouse cerebellum.
      Interestingly, quantitative ISHH revealed differential changes in alpha 1G
      expression in the leaner cerebellum, where the granule cell layer showed
      decreased alpha 1G expression while Purkinje cells showed increased alpha 1G
      expression. To confirm these observations, the granule cell layer and the
      Purkinje cell layer were laser capture microdissected separately, then analyzed
      with qRT-PCR. Similar to the observation obtained by ISHH, the leaner granule
      cell layer showed decreased alpha 1G expression and the leaner Purkinje cell
      layer showed increased alpha 1G expression. These results suggest that
      differential expression of T-type calcium channels in the leaner cerebellum may
      be involved in the observed movement disorders.

PMID- 15514989
TI  - A two-phase growth strategy in cultured neuronal networks as reflected by the
      distribution of neurite branching angles.
AB  - Neurite outgrowth and branching patterns are instrumental in dictating the wiring
      diagram of developing neuronal networks. We study the self-organization of single
      cultured neurons into complex networks focusing on factors governing the
      branching of a neurite into its daughter branches. Neurite branching angles of
      insect ganglion neurons in vitro were comparatively measured in two neuronal
      categories: neurons in dense cultures that bifurcated under the presence of
      extrinsic (cellular environment) cues versus neurons in practical isolation that
      developed their neurites following predominantly intrinsic cues. Our experimental
      results were complemented by theoretical modeling and computer simulations. A
      preferred regime of branching angles was found in isolated neurons. A model based
      on biophysical constraints predicted a preferred bifurcation angle that was
      consistent with this range shown by our real neurons. In order to examine the
      origin of the preferred regime of angles we constructed simulations of neurite
      outgrowth in a developing network and compared the simulated developing neurons
      with our experimental results. We tested cost functions for neuronal growth that
      would be optimized at a specific regime of angles. Our results suggest two phases
      in the process of neuronal development. In the first, reflected by our isolated
      neurons, neurons are tuned to make first contact with a target cell as soon as
      possible, to minimize the time of growth. After contact is made, that is, after
      neuronal interconnections are formed, a second branching strategy is adopted,
      favoring higher efficiency in neurite length and volume. The two-phase
      development theory is discussed in relation to previous results.

PMID- 15514990
TI  - Asphyxiating tracheal bronchogenic cyst.
AB  - We report on a 7-month old infant with severe respiratory distress secondary to a
      paratracheal bronchogenic cyst. Respiratory relief was achieved by transtracheal
      puncture of the cyst. Surgical removal of the cyst was performed 1 week later
      because of radiological evidence of reaccumulation of fluid.

PMID- 15514991
TI  - Cyclic nucleotide phosphodiesterases and their role in immunomodulatory
      responses: advances in the development of specific phosphodiesterase inhibitors.
AB  - The activity of phosphodiesterases (PDEs) is associated with a wide variety of
      diseases and an intense effort toward the development of specific PDEs inhibitors
      has been generated for the last years. They are the enzymes responsible for the
      hydrolysis of intracellular cyclic adenosine and guanosine monophosphate, and
      their complexity, as well as their different functional role, makes these enzymes
      a very attractive therapeutic target. This review is focused on the role of PDEs
      played on immunomodulatory processes and the advance on the development of
      specific inhibitors, covering PDEs mainly related to the regulation of autoimmune
      processes, PDE4 and PDE7. The review also highlights the novel structural classes
      of PDE4 and PDE7 inhibitors, and the therapeutic potential that combined
      PDE4/PDE7 inhibitors offer as immunomodulatory agents.

PMID- 15514992
TI  - Neuroendocrine mechanism for tolerance to cerebral ischemia-reperfusion injury in
      male rats.
AB  - Testosterone has been shown to exacerbate cerebral ischemia-reperfusion injury,
      which suggests that the well-known stress-induced testosterone reduction could be
      a protective response. We hypothesized that stress-induced testosterone reduction
      contributes to ischemia tolerance in cerebral ischemia-reperfusion injury in male
      rats. In intact male rats, stress was induced by brief anesthesia at 6 h before
      transient middle cerebral artery occlusion (MCAO). Testosterone levels were
      significantly decreased 6 h after stress. Testosterone reduction was associated
      with a 50% reduction in cerebral lesion volume in the stressed animals. Further,
      the stress-induced cerebral ischemia tolerance was eliminated by testosterone
      replacement in castrated males. Immunohistochemical staining showed that androgen
      receptors were up-regulated after cerebral ischemia-reperfusion injury and
      partially colocalized with terminal deoxynucleotidyl transferase dUTP nick end
      labeling (TUNEL) positive cells in the parietal cortex and extensively
      colocalized in the caudate putamen. Heat shock protein 70 (Hsp70) and 90 (Hsp90)
      are involved in ischemia tolerance, and were not colocalized with TUNEL in the
      immunohistochemical staining, suggesting an antiapoptotic role of Hsp's. To
      determine the effect of testosterone on MCAO-induced Hsp70 and -90 expression, a
      testosterone replacement or withdrawal paradigm was used. Testosterone-replaced
      animals exhibited a decrease in Hsp expression, whereas testosterone withdrawal
      (mimicking the stress-induced testosterone suppression) normalized this deficit.
      In summary, stress-induced testosterone reduction contributes to ischemia
      tolerance in cerebral ischemia-reperfusion injury in males, which could be
      related to the loss of inhibition by testosterone of Hsp70 and -90 expression.

PMID- 15514993
TI  - Systematic screening and identification of antigens recognized by monoclonal
      antibodies raised against the developing lateral olfactory tract.
AB  - During development, olfactory bulb axons navigate a complex microenvironment
      composed of myriad molecules to construct a bundle called the lateral olfactory
      tract. The axons themselves also express thousands of different molecules. In the
      present study, we produced and characterized six monoclonal antibodies that label
      the lateral olfactory tract and its surroundings in a unique pattern. The
      labeling profiles suggested that the antigen molecules recognized by each
      antibody are heterogeneously distributed around the developing lateral olfactory
      tract. We developed an efficient screening method to identify the antigen
      molecules by combining expression of a cDNA library in COS-7 cells and the
      subsequent immunohistochemical staining of the cells. The systematic screening
      successfully identified specific cDNA clones for all of the monoclonal
      antibodies, which highly probably coded for the antigen molecules, and therefore
      unveiled the molecular nature of local components that embrace the developing
      lateral olfactory tract in mice.

PMID- 15514997
TI  - Expression of muscarinic acetylcholine receptors and choline acetyltransferase
      enzyme in cultured antennal sensory neurons and non-neural cells of the
      developing moth Manduca sexta.
AB  - Antennal sensory neurons of Manduca sexta emerge from epidermal cells that also
      give rise to sheath cells surrounding the peripheral parts of the neurons and to
      glial cells that enwrap the sensory axons in the antennal nerve. Reciprocal
      interactions between sensory neurons and glial cells are believed to aid in axon
      growth and guidance, but the exact nature of these interactions is not known. We
      investigated the possibility of cholinergic interactions in this process by
      locating muscarinic acetylcholine receptors (mAChRs) and choline
      acetyltransferase (ChAT) enzyme in cultured antennal sensory neurons and non
      neural cells. ChAT and mAChRs were present in the sensory neurons from the first
      day in culture. Therefore, the sensory neurons are probably cholinergic, as
      previously suggested, but they may also be controlled by ACh. In 7-day-old
      cultures a subgroup of small non-neural cells with processes expressed ChAT
      activity, and in 14-day-old cultures non-neural cells that formed lamellipodia
      and scaffoldlike structures on the culture substrate were labeled with ChAT
      antibody. mAChR activity was detected in similar non-neural cells but only in
      areas surrounding the nuclei. In addition, mAChRs were found in flat lamellipodia
      and filopodia forming cells that were present in 1-day-old cultures and grew in
      size during the 2 week investigation period. These findings suggest muscarinic
      cholinergic interactions between the neural and non-neural cells during the
      development of Manduca antenna.

PMID- 15514998
TI  - BDNF regulates primary dendrite formation in cortical neurons via the PI3-kinase
      and MAP kinase signaling pathways.
AB  - Neurotrophins are known to regulate dendritic development, but the mechanisms
      that mediate neurotrophin-dependent dendrite formation are largely unknown. Here
      we show that brain-derived neurotrophic factor (BDNF) induces the formation of
      primary dendrites in cortical neurons by a protein synthesis-independent
      mechanism. BDNF leads to the rapid activation of PI3-kinase, MAP kinase, and PLC
      gamma in cortical neurons, and pharmacological inhibition of PI3-kinase and MAP
      kinase in dissociated cell cultures and cortical slice cultures suppresses the
      ability of BDNF to induce dendrite formation. A constitutively active form of PI3
      kinase, but not MEK, is sufficient to induce primary dendrite formation in
      cortical neurons. These observations indicate that BDNF induces primary dendrite
      formation via activation of the PI3-kinase and MAP kinase pathways and provide
      insight into the mechanisms that mediate the morphological effects of
      neurotrophin signaling.

PMID- 15514999
TI  - Expression and function of two nicotinic subunits in insect neurons.
AB  - Nicotinic acetylcholine receptors (nAChRs) in insects are neuron-specific
      oligomeric proteins essential for the central transmission of sensory
      information. Little is known about their subunit composition because it is
      difficult to express functional insect nAChRs in heterologous systems. As an
      alternative approach we have examined the native expression of two subunits in
      neurons of the nicotinic-resistant, tobacco-feeding insect Manduca sexta. Both
      the alpha-subunit MARA1 and the beta-subunit MARB can be detected by in situ
      hybridization in the majority of cultured neurons with an overlapping, but not
      identical, distribution. Changes in intracellular Ca(2+) evoked by nicotinic
      stimulation are more strongly correlated to the expression of MARA1 than MARB and
      are independent of cell size. Unlike the previously reported critical role of
      MARA1 in mediating nicotinic Ca(2+) responses, down-regulation of MARB by RNA
      interference (RNAi) did not reduce the number of responding neurons or the size
      of evoked responses, suggesting that additional subunits remain to be identified
      in Manduca.

PMID- 15515000
TI  - Sex and species differences in neuromodulatory input to a premotor nucleus: a
      comparative study of substance P and communication behavior in weakly electric
      fish.
AB  - Many electric fish species modulate their electric organ discharges (EODs) to
      produce transient social signals that vary in number and structure. In
      Apteronotus leptorhynchus, males modulate their EOD more often than females,
      whereas in Apteronotus albifrons, males and females produce similar numbers of
      modulations. Sex differences in the number of EOD modulations in A. leptorhynchus
      are associated with sex differences in substance P in the diencephalic nucleus
      that controls transient EOD modulations, the CP/PPn. These sex differences in
      substance P have been hypothesized to regulate sex differences in the production
      of EOD modulations. To comparatively test this hypothesis, we examined substance
      P immunoreactivity in the CP/PPn of male and female A. leptorhynchus and A.
      albifrons. Because the number of EOD modulations is sexually monomorphic in A.
      albifrons, we predicted no sex difference in substance P in the CP/PPn of this
      species. Contrary to this prediction, male A. albifrons had significantly more
      substance P in the CP/PPn than females. This suggests that sex differences in
      substance P are not sufficient for controlling sex differences in the number of
      EOD modulations. Modulation structure (frequency excursion and/or duration),
      however, is also sexually dimorphic in A. leptorhynchus and is another possible
      behavioral correlate of the sexually dimorphic distribution of substance P. The
      present study found pronounced sex differences in the structure of EOD
      modulations in A. albifrons similar to those in A. leptorhynchus. Thus, sex
      differences in substance P may influence sex differences in the structure, rather
      than the number, of EOD modulations.

PMID- 15515001
TI  - Peripheral neuropathy in hepatitis-related mixed cryoglobulinemia:
      electrophysiologic follow-up study.
AB  - A retrospective study was performed on 27 patients with hepatitis C (HCV)-related
      mixed cryoglobulinemia (purpura, arthralgia, hepatitis, glomerulonephritis,
      peripheral neuropathy) to assess peripheral nerve involvement during follow-up of
      up to 8 years. All patients had the same degree of organ/system involvement
      initially and were clinically evaluated at least annually. All 27 patients
      received steroids; 15 also received recombinant interferon-alpha 2b (rIFN-alpha
      2b). At first examination, neurological signs and electrodiagnostic findings
      consistent with peripheral neuropathy were found in 20 (74%) and in 24 (88.8%)
      patients, respectively. Neurological evaluation and electrodiagnostic data at 3
      and 8 years revealed worsening of neuropathy, whereas the other manifestations of
      mixed cryoglobulinemia (MC) were stable. At the last examination, clinical and
      electrodiagnostic signs of neuropathy were found in 25 patients (92.5%),
      occurring in 1 of 3 patients with normal initial findings, and worsened in 8. A
      more severe neuropathy was observed in 3 (25%) of the patients treated with
      prednisone alone and in 6 (40%) of the patients additionally treated with rIFN
      alpha 2b. Our data confirm that in patients with HCV-related MC, peripheral nerve
      involvement is frequent, is progressive, and does not seem to benefit by addition
      of rIFN-alpha 2b to steroid treatment.

PMID- 15515002
TI  - Positional cloning and characterization of mouse mei8, a disrupted allelle of the
      meiotic cohesin Rec8.
AB  - A novel mutation, mei8, was isolated in a forward genetic screen for infertility
      mutations induced by chemical mutagenesis of ES cells. Homozygous mutant mice are
      sterile. Mutant females exhibit ovarian dysgenesis and lack ovarian follicles at
      reproductive maturity. Affected males have small testes due to arrest of
      spermatogenesis during meiotic prophase I. Genetic mapping and positional cloning
      of mei8 led to the identification of a mutation in Rec8, a homolog of the yeast
      meiosis-specific cohesin gene REC8. Analysis of meiosis in Rec8(mei8)/Rec8(mei8)
      spermatocytes showed that, while initiation of recombination and synapsis occurs,
      REC8 is required for the completion and/or maintenance of synapsis, cohesion of
      sister chromatids, and the formation of chiasmata, as it is in other organisms.
      However, unlike yeast and Caenorhabditis elegans, localization of REC8 on meiotic
      chromosomes is not required for the assembly of axial elements.

PMID- 15515004
TI  - Aversive stimulation of the inferior colliculus changes dopamine and serotonin
      extracellular levels in the frontal cortex: modulation by the basolateral nucleus
      of amygdala.
AB  - We have shown that stimulation of the neural substrates in the inferior
      colliculus (IC) causes a significant increase in the extracellular levels of
      dopamine (DA) in frontal cortex (FC). Also, it has been reported that the
      basolateral complex of the amygdala (BLA) serves as a filter for unconditioned
      and conditioned aversive information that ascend to higher structures from the
      brainstem. Linking these two kinds of information, this work examines whether
      inactivation of BLA interferes with the activation of cortical dopaminergic
      outputs produced by aversive stimulation of the IC. To this end, rats were
      implanted with an electrode in the IC for the determination of the threshold of
      escape responses. Each rat also bore a cannula implanted in the BLA for
      injections of lidocaine (10 microg/0.5 microL), muscimol (0.5 microg/0.5 microL),
      or its vehicle and a microdialysis probe in the FC for determination of the
      amount of DA and serotonin (5-HT). The data obtained show that IC electrical
      stimulation caused an increase in the DA release while it reduced the 5-HT
      release in the FC. BLA inactivation with both lidocaine or muscimol enhanced the
      aversiveness of the electrical stimulation of the IC and attenuated the increase
      in DA, while the reduction in 5-HT release in the FC remained unaffected. These
      findings suggest that ascending aversive information from IC on their way up to
      higher structures in the SNC courses with opposite modulation by DA/5-HT
      mechanisms in the FC. These processes are regulated by filters located in the
      BLA. It is proposed that the loss of these BLA regulatory mechanisms prevents the
      expression of these modulatory mechanisms in the FC that are adaptive responses
      in order to cope with unconditioned aversive stimulus triggered at the brainstem
      level.

PMID- 15515005
TI  - Internuclear synapse in the amygdala is not facilitated in fear conditioning.
AB  - The amygdala is essential for fear learning and memory. Synaptic transmission is
      enhanced in two pathways in the amygdala in fear conditioning. In this study we
      examined whether lateral (LA) to basolateral (BLA) amygdala synapses are
      potentiated and participate in intra-amygdala plasticity during the maintenance
      of fear memory. Our data showed that synaptic strength from the LA
      (ventrolateral) to the BLA (parvicellular) pathway was not increased after fear
      conditioning and suggests that this pathway does not integrate information
      relevant to the coding of memories in auditory fear learning.

PMID- 15515006
TI  - Fibrotic valvular heart disease is not related to chemical class but to
      biological function: 5-HT2B receptor activation plays crucial role.

PMID- 15515007
TI  - BDNF enhancement of postsynaptic NMDA receptors is blocked by ethanol.
AB  - The neurotrophin brain-derived neurotrophic factor (BDNF) modulates several
      distinct aspects of synaptic transmission. Physiological and biochemical evidence
      implicates the NMDA glutamate receptor as one of the targets for BDNF modulation.
      In the present studies, murine brain slices containing hippocampus and neocortex
      were used to study the effects of BDNF on excitatory neurotransmission. Acute
      exposure to BDNF rapidly and reversibly enhanced the magnitude of NMDA-mediated,
      but not AMPA receptor-mediated, synaptic currents, specifically enhancing the
      activity of NMDA receptors containing the NR2B subunit. This effect of BDNF was
      dependent on activation of trkB neurotrophin receptors because similar effects
      were not seen with the related neurotrophins NT-3 or NGF. Furthermore, activation
      of trkB receptors in the postsynaptic neuron was required, as BDNF-induced
      potentiation was blocked by postsynaptic injection of a trk tyrosine kinase
      inhibitor. Interestingly, the effect of BDNF was also completely blocked by
      pretreatment with ethanol, even at concentrations of ethanol that had minimal
      direct effects on NMDA-mediated responses. These results provide a potential
      mechanism for the proposed role for BDNF in activity-dependent synaptic
      plasticity and, potentially, learning and memory processes.

PMID- 15515008
TI  - Water vapor sorption of hot-melt extruded hydroxypropyl cellulose films: effect
      on physico-mechanical properties, release characteristics, and stability.
AB  - Hot-melt extrusion technology was used to prepare thin polymer films containing
      hydroxypropyl cellulose and clotrimazole (CT). Films containing hydroxypropyl
      celluloses of different molecular weight and the drug were investigated for
      moisture-sorption, mechanical properties, and release characteristics. Stability
      of the films was also studied at 25 degrees C/60% relative humidity (RH) and 40
      degrees C/75% RH for up to 3 months. To study the moisture-sorption of the hot
      melt extruded films, a rapid dynamic vapor sorption technique was used.
      Mechanical properties were evaluated using the Texture Analyzer. The molecular
      weight of the polymer had a significant effect on the mechanical and release
      characteristics of the films but did not influence the equilibrium moisture
      content in the films stored at RHs ranging from 0 to 90%. However, the time to
      reach equilibrium was longer for the higher molecular weight polymers. The drug
      release rate was dependent on the rate of erosion, which in turn depended on the
      molecular weight of the polymer. The films were stable at 25 degrees C/60% RH for
      up to 3 months with no significant degradation or recrystallization of CT.
      However, recrystallization of the drug was observed within the films stored in
      accelerated stability conditions at the end of 3 months in which only 92.9% (+/
      1.9) CT remained.

PMID- 15515009
TI  - Valvular heart disease and fibrotic reactions may be related to ergot dopamine
      agonists, but non-ergot agonists may also not be spared.

PMID- 15515010
TI  - Postnatal neurogenesis in the dentate gyrus of the guinea pig.
AB  - In all species examined, the dentate gyrus develops over an extended period that
      begins during gestation and continues up to adulthood. The aim of this study was
      to investigate the pattern of postnatal cell production in the dentate gyrus of
      the guinea pig, a rodent whose brain development has features more closely
      resembling the human condition than the most commonly used rodents (rat and
      mouse). Animals of different postnatal (P) ages received one or multiple
      injections of bromodeoxyuridine (BrdU), and the number of labeled cells in the
      dentate gyrus was counted after time intervals of 24 h or longer. The total
      granule cell number and the volume of the granule cell layer were evaluated in
      Nissl-stained brain sections from P1 and P30 animals. P1-P5 animals were treated
      with MK-801 to analyze the effect of NMDA receptor blockade on cell
      proliferation. Cell production occurred at a high rate (9,000-13,000 labeled
      cells 24 h after one injection) from P1 to P20, with a peak at 3-6 days of age,
      and then slowly declined from P20 to P30. The production of new cells continued
      in adult animals, although at a much-reduced rate (400 cells 24 h after one
      injection). About 20% of the labeled cells survived after a 17-day period and
      most (60%) of these cells had a neuronal phenotype. The total number of granule
      cells increased over the first postnatal month; in 30-day-old animals, it was 20%
      greater than in 1-day-old animals. Administration of MK-801 to P1-P5 animals
      caused an increase in cell proliferation restricted to the dorsal dentate gyrus.
      The present data show that, although the guinea pig dentate gyrus develops
      largely before birth, the production of new neurons continues at a high rate
      during the first postnatal month, leading to a considerable increase in cell
      number. This developmental pattern, resembling the human and nonhuman primate
      condition, may make the guinea pig a useful rodent model in developmental studies
      on dentate gyrus neurogenesis.

PMID- 15515011
TI  - Two- and three-dimensional QSAR of carrier-mediated transport of beta-lactam
      antibiotics in Caco-2 cells.
AB  - In this study, we investigated whether such a topological descriptor-based
      approach is suitable for predicting the carrier-mediated transport of 20 beta
      lactam antibiotics that are substrates of peptide transporters. To select the
      molecular descriptors that can effectively predict a targeted property in QSAR
      analysis, the genetic algorithm-combined partial least squares approach was used.
      The feasibility of the two-dimensional (2D)-QSAR approach was compared with that
      of comparative molecular field analysis (CoMFA). The logarithm of the uptake
      values of 20 beta-lactam antibiotics in Caco-2 cells obtained from the literature
      ranged from -1.15 to 1.09 (nmol/cm2/2 h). When preliminary leave-one-out cross
      validated partial least squares analyses implemented in the SYBYL/CoMFA program
      were conducted, the r2pred was 0.759 and the standard error of prediction (s) was
      0.373. However, the 2D-QSAR approach based on Molconn-Z descriptors gave a better
      predictability (r2pred = 0.923, s = 0.211), where 14 descriptors were selected
      and the optimal number of principal components was 4. Considering that the 2D
      topological descriptors are less computationally intensive and practically
      completely automated, the simple 2D-QSAR model is also of great importance in
      drug discovery settings.

PMID- 15515012
TI  - Molecular margin analysis predicts local recurrence after sublobar resection of
      lung cancer.
AB  - Sublobar resection for early-stage lung cancer has been used for patients who are
      not candidates for lobar resection. However, sublobar resection is associated
      with high local recurrence rates in the context of tumor-free parenchymal
      margins. The mechanism underlying this high recurrence rate is not well
      understood. We hypothesized that this elevated risk of local recurrence is due to
      undetected tumor cells present at parenchymal margins thought to be negative by
      conventional light microscopy. Thirteen of 44 patients who underwent sublobar
      resection for lung cancer were found to have a k-ras mutation at codon 12.1. A
      novel fluorescence-based assay for detection of rare copies of mutant DNA in a
      background of wild-type DNA, fluorescent gap ligase chain reaction, was used to
      quantitate the mutant/wild-type DNA in a range of 1 to 1/10,000 in histologically
      normal margins from these resections. Nine of 13 patients had at least one margin
      with the number of mutant cells over or equal to a threshold of 1/5,000, and of
      these, 6/9 (67%) recurred locally. None of the remaining 4 patients without
      mutant DNA in any surgical margin had evidence of recurrence. The higher rate of
      local recurrence associated with sublobar resection of lung cancer is likely due
      to the occult presence of tumor cells at resection margins. These occult tumor
      cells can be quantitated using a novel fluorescence-based assay and define a
      group of patients at high risk for local recurrence who are candidates for
      adjuvant therapy or more extensive resection. This methodology may be adaptable
      to a real-time format for intraoperative use.

PMID- 15515013
TI  - Involvement of the tumor necrosis factor (TNF)/TNF receptor system in leukemic
      cell apoptosis induced by histone deacetylase inhibitor depsipeptide (FK228).
AB  - Inhibition of histone deacetylase (HDAC) is a novel strategy for the treatment of
      leukemias via restoration of aberrantly silenced genes. In this study, we
      conducted a detailed analysis of anti-leukemic effects of an HDAC inhibitor
      (HDI), depsipeptide (FK228), using myeloid leukemia cell lines HL-60 and K562.
      DNA chip analysis revealed upregulation of TNF-alpha mRNA and a number of
      molecules involved in TNF-signaling such as TRAF-6, caspases-10, and -7 in
      depsipeptide-treated HL-60 cells, which prompted us to examine the involvement of
      the TNF/TNF receptor system in the anti-leukemic effects of the drug.
      Upregulation of TNF-alpha was induced by depsipeptide in HL-60 and K562 cells,
      which expressed type I TNF receptors (TNF-RI). Depsipeptide activated caspases-8
      and -10, which in turn cleave caspases-3 and -7, leading to apoptotic cell death
      in both cell lines. Anti-TNF-alpha neutralizing antibody and short interfering
      RNA (siRNA) against TNF-RI alleviated the activation of the caspase cascade and
      the induction of apoptosis, indicating the presence of an autocrine loop.
      Finally, we demonstrated that the enhanced production of TNF-alpha by
      depsipeptide was due to transcriptional activation of the TNF-alpha gene through
      hyperacetylation of histones H3 and H4 in its promoter region (-208 to +35).
      These results suggest that autocrine production of TNF-alpha plays a role in the
      cytotoxicity of depsipeptide against a subset of leukemias.

PMID- 15515014
TI  - Cell size-dependent and independent proliferation of rodent neuroblastoma x
      glioma cells.
AB  - For decades, the connection between cell size and division has been the subject
      of controversy. While in yeast, cell size checkpoints coordinate cellular growth
      with cell-cycle progression, it has been recently shown that large and small
      Schwann cells proliferate at the same rate (Conlon and Raff, 2003, J Biol 2:7).
      From this point of view, it is important to know whether normal and tumoral cells
      are similar. During continuous culture of NG108-15 neuroblastoma x glioma cells,
      the rate of proliferation, cell size, and external pH changed in parallel. At
      constant pH, the cell size-proliferation relationship followed a bell-shaped
      curve, so that proliferation was optimal within a cell volume window. In
      contrast, external acidification decreased proliferation independently of cell
      size. Using electrophysiological techniques, we showed that changes in cell size
      were dependent on both the uptake of nutrients and the passive influx of ions.
      Furthermore, an increase in cell size was associated with an increase in total
      proteins/cell. Another way to influence cell growth and proliferation is to alter
      the activity of the PI-3 kinase and target of rapamycin (TOR) signaling pathway.
      In NG108-15 cells, pharmacological inhibition of these proteins with LY 294002
      and rapamycin respectively decreased proliferation but did not modify cell size.
      In contrast, aphidicolin treated cells did not proliferate, but they continued to
      increase in size. Altogether these results indicate that the proliferation of
      NG108-15 cells is controlled by both cell size-dependent and independent
      mechanisms that include extracellular pH and PI-3 kinase activity.

PMID- 15515015
TI  - Differential carnitine/acylcarnitine translocase expression defines distinct
      metabolic signatures in skeletal muscle cells.
AB  - Import of acylcarnitine into mitochondrial matrix through carnitine/acylcarnitine
      translocase (CACT) is fundamental for lipid catabolism. To probe the effect of
      CACT down-expression on lipid metabolism in muscle, human myocytes were stably
      transfected with CACT-antisense construct. In presence of low concentration of
      palmitate, transfected cells showed decreased palmitate oxidation and acetyl
      carnitine content, increased palmitoyl-carnitine level, and reduced insulin
      dependent decrease of fatty acylcarnitine-to-fatty acyl-CoA ratio. The augmented
      palmitoyl-carnitine synthesis, also in the presence of insulin, could be related
      to an altered regulation of carnitine-palmitoyl-transferase 1 (CPT 1) by malonyl
      CoA, whose synthesis is dependent by the availability of cytosolic acetyl-groups.
      Indeed, all the described effects were completely overcome by CACT neo-expression
      by recombinant adenovirus vector or by addition of acetyl-carnitine to cultures.
      Acetyl-carnitine effect was related to an increase of malonyl-CoA and was
      abolished by down-expression, via antisense RNA strategy, of acetyl-CoA
      carboxylase-beta, the mitochondrial membrane enzyme involved in the direct CPT 1
      inhibition via malonyl-CoA synthesis. Thus, in our experimental model the
      modulation of CACT expression has consequences for CPT 1 activity, while the
      biologic effects of acetyl-carnitine are not associated with a generic supply of
      energy compounds but to the anaplerotic property of the molecule.

PMID- 15515016
TI  - Screening for family members of patients with nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma (NPC) is well known for its peculiarly skewed
      distribution with highest incidence in Southern Chinese population. Familial
      aggregation is evident, hence screening for early detection is offered by
      oncology centers in Hong Kong to first-degree relatives of patients with NPC.
      During the period 1994-2001, 929 family members were screened in our center. The
      screenees were advised to attend an annual examination that includes serological
      test against Epstein Barr Virus (EBV), physical examination to exclude cervical
      lymphadenopathy and cranial nerve palsy, and endoscopic examination of the
      nasopharyngeal region. Two different methods were used for the serology test:
      indirect immuno-fluorescent (IF) test for IgA against viral capsid antigen; and
      starting in 1997 enzyme-linked immunosorbent assay (ELIZA) against nuclear
      antigen and viral capsid antigen. Twelve cases of nasopharyngeal carcinoma were
      diagnosed, giving a detection rate of 5/1,155 (433/100,000) person-year for male
      and 7/1,404 (499/100,000) person-year for female participants observed. The
      corresponding average annual incidence in Hong Kong during this period was 24.1
      and 9.6 per 100,000, respectively. Forty-one percent of these detected cases had
      Stage I disease, whereas only 2% of patients referred to the department for
      primary treatment presented with such early disease. Six cases were detected at
      first visit, and all were EBV-positive. Another 78 screenees with positive
      serology at first visit were followed up for 204 person years, and thus far NPC
      was detected in 3 after an interval of 6-32 months. Of the 845 initially EBV
      negative screenees followed up for 2,337 person-years, NPC was detected in 3
      after an interval of 12-45 months. One showed sero-conversion at the time of
      diagnosis. We conclude that family members of known patients do show a
      substantially higher risk of developing NPC, and regular screening by current
      method improves the chance of early detection.

PMID- 15515017
TI  - Cervical cancer in the Netherlands 1989-1998: Decrease of squamous cell carcinoma
      in older women, increase of adenocarcinoma in younger women.
AB  - Cervical cancer is a preventable disease, occurring in relatively young women. In
      the Netherlands, population-based cervical screening aims at women aged 30-60
      years. We performed a population-based study of the incidence of invasive
      cervical cancer in the Netherlands to evaluate trends, with emphasis on age at
      time of diagnosis. Histologic diagnosis was retrieved from the Netherlands Cancer
      Registry for all women residing in the Netherlands with invasive cervical cancer
      between January 1, 1989, and December 31, 1998. In this 10-year period, the
      incidence rate of squamous cell carcinoma decreased significantly from
      7.1/100,000 to 6.1/100,000 (p < 0.001), with the greatest decrease in women aged
      60-74 (-5.5%). While the overall incidence rate of adenocarcinoma remained
      stable, it increased in women aged 15-29 (+15.8%) and in women aged 30-44
      (+2.5%), though the number of cases was small. For squamous cell carcinoma, the
      incidence of stage II at diagnosis decreased most (-2.7%). There was no change in
      stage at diagnosis for adenocarcinoma. Most cases of cervical cancer, 60.5%, were
      detected between ages 30 and 60 years, i.e., the Dutch screening age interval.
      Cervical cancer in women below age 30 contributed 5.0% to the total incidence,
      with 3.0% occurring between ages 27 and 29. Thus, screening for cervical cancer
      in the Netherlands is associated with a decrease in the incidence of squamous
      cell carcinoma and adenocarcinoma incidence appears to be increasing in younger
      women.

PMID- 15515018
TI  - Parathyroid adenoma and primary CNS tumors.
AB  - Hyperparathyroidism onset at a young age is one feature in multiple endocrine
      neoplasia (MEN) type 1 and MEN type 2A cancer syndromes. There are several case
      reports of MEN Type 1-associated central nervous system (CNS) tumors. To
      determine if there is an association between parathyroid adenomas and CNS tumors,
      we used Swedish registry data to identify all individuals operated on for
      parathyroid adenomas between 1958-99 (n = 12,468). Follow-up for the occurrence
      of CNS tumors in these individuals was through linkage with the Swedish Cancer
      Registry. There were 70 observed cases of a CNS tumor diagnosed after a
      parathyroid adenoma, to be compared to 35 expected (standard incidence ratio
      [SIR] = 2.0; 95% confidence interval [CI] = 1.5-2.5). This increased risk was
      independent of duration of follow-up and was confined to meningiomas (SIR = 2.4,
      95% CI = 1.7-3.4) and neurinomas (SIR = 3.4, 95% CI = 1.5-6.8). These results
      strongly indicate an association between these tumor forms that may be genetic,
      environmental (such as radiation) or a combination of both.

PMID- 15515019
TI  - Characterization of human PA2.26 antigen (T1alpha-2, podoplanin), a small
      membrane mucin induced in oral squamous cell carcinomas.
AB  - We report the full cDNA sequence encoding the human homologue of murine PA2.26
      (T1alpha-2, podoplanin), a small mucin-type transmembrane glycoprotein originally
      identified as a cell-surface antigen induced in keratinocytes during mouse skin
      carcinogenesis. The human PA2.26 gene is expressed as 2 transcripts of 0.9 and
      2.7 kb in several normal tissues, such as the placenta, skeletal muscle, heart
      and lung. Using a specific polyclonal antibody raised against a synthetic peptide
      of the protein ectodomain, PA2.26 was immunohistochemically detected in about 25%
      (15/61) of human early oral squamous cell carcinomas. PA2.26 distribution in the
      tumours was heterogeneous and often restricted to the invasive front. Double
      immunofluorescence and confocal microscopy analysis showed that PA2.26
      colocalized with the membrane cytoskeleton linker ezrin at the surface of tumour
      cells and that its presence in vivo was associated with downregulation of
      membrane E-cadherin protein expression. Ectopic expression of human PA2.26 in
      HeLa carcinoma cells and immortalized HaCaT keratinocytes promoted a
      redistribution of ezrin to the cell edges, the formation of cell-surface
      protrusions and reduced Ca(2+)-dependent cell-cell adhesiveness. These results
      point to PA2.26 as a novel biomarker for oral squamous cell carcinomas that might
      be involved in migration/invasion.

PMID- 15515020
TI  - Distribution of prospective glutamatergic, glycinergic, and GABAergic neurons in
      embryonic and larval zebrafish.
AB  - Zebrafish are an excellent model for studies of the functional organization of
      neuronal circuits, but little is known regarding the transmitter phenotypes of
      the neurons in their nervous system. We examined the distribution in spinal cord
      and hindbrain of neurons expressing markers of transmitter phenotype, including
      the vesicular glutamate transporter (VGLUT) genes for glutamatergic neurons, the
      neuronal glycine transporter (GLYT2) for glycinergic neurons, and glutamic acid
      decarboxylase (GAD65/67) for GABAergic neurons. All three markers were expressed
      in a large domain in the dorsal two-thirds of spinal cord, with additional, more
      ventral expression domains for VGLUT2 and GAD/GABA. In the large dorsal domain,
      dual in situ staining showed that GLYT2-positive cells were intermingled with
      VGLUT2 cells, with no dual-stained neurons. Many of the neurons in the dorsal
      expression domain that were positive for GABA markers at embryonic stages were
      also positive for GLYT2, suggesting that the cells might use both GABA and
      glycine, at least early in their development. The intermingling of neurons
      expressing inhibitory and excitatory markers in spinal cord contrasted markedly
      with the organization in hindbrain, where neurons expressing a particular marker
      were clustered together to form stripes that were visible running from rostral to
      caudal in horizontal sections and from dorsomedial to ventrolateral in cross
      sections. Dual labeling showed that the stripes of neurons labeled with one
      transmitter marker alternated with stripes of cells labeled for the other
      transmitter phenotypes. The differences in the distribution of excitatory and
      inhibitory neurons in spinal cord versus hindbrain may be tied to differences in
      their patterns of development and functional organization.

PMID- 15515021
TI  - Directing pluripotent cell differentiation using "diced RNA" in transient
      transfection.
AB  - Embryonic stem (ES) and embryonic carcinoma (EC) cells are pluripotent and have
      the capacity to differentiate into many cell types. The ability to direct their
      differentiation should have considerable practical applications. Here, we first
      report the use of diced short interfering RNAi against Oct4 in a transient
      approach, to direct differentiation of ES towards the trophectoderm lineage. We
      then apply this approach to downregulate Smad4 in mouse P19 EC cells. We have
      found that this leads to an increase in the levels of Pax6 (a neuroectoderm
      marker), reduction in the levels of Brachyury (a mesoderm marker), and a 3-fold
      increase in the number of betaIII tubulin-positive colonies when these cells were
      allowed to differentiate. This indicates a redirection of cell fate towards the
      neuroectoderm lineage. Thus, transient RNAi could provide a valuable tool to
      direct pluripotent cells along specific pathways of differentiation while
      circumventing permanent genetic changes.

PMID- 15515022
TI  - Ontogeny and innervation patterns of dopaminergic, noradrenergic, and
      serotonergic neurons in larval zebrafish.
AB  - We report the development of aminergic neurons from 0-10 days postfertilization
      (dpf) in zebrafish (Danio rerio). This study was prompted by the lack of
      information regarding patterns of spinal aminergic innervation at early stages,
      when the fish are accessible to optical, genetic, and electrophysiological
      approaches toward understanding neural circuit function. Our findings suggest
      that aminergic populations with descending processes are among the first to
      appear during development. Descending aminergic fibers, revealed by antibodies to
      tyrosine hydroxylase (TH) and serotonin (5-hydroxytryptamine; 5-HT), innervate
      primarily the ventral (TH, 5-HT), but also the dorsal (5-HT) aspects of the
      spinal cord by 4 dpf, with the extent of innervation not changing markedly up to
      10 dpf. By tracking the spatiotemporal expression of TH, 5-HT, and dopamine beta
      hydroxylase reactivity, we determined that these fibers likely originate from
      neurons in the posterior tuberculum (dopamine), the raphe region (5-HT) and,
      possibly, the locus coeruleus (noradrenaline). In addition, spinal neurons
      positive for 5-HT emerge between 1-2 dpf, with processes that appeared to descend
      along the ventrolateral cord for only 1-2 muscle segments. Their overall
      morphology distinguished these cells from previously described "VeMe"
      (ventromedial) interneurons, which are also located ventromedially, but have
      long, multisegmental descending processes. We confirmed the distinction between
      spinal serotonergic and VeMe interneurons using fish genetically labeled with
      green fluorescent protein. Our results suggest that the major aminergic systems
      described in adults are in place shortly after hatching, at a time when zebrafish
      are accessible to a battery of techniques to test neuronal function during
      behavior.

PMID- 15515023
TI  - Transgenic mice expressing a fluorescent in vivo label in a distinct
      subpopulation of neocortical layer 5 pyramidal cells.
AB  - The neuronal components of cortical circuits have been characterized on the basis
      of their morphological and functional properties, and further refined by
      correlation of marker proteins with particular cell types. This latter approach
      has been very fruitful for GABA-containing neurons, but comparable diagnostic
      markers for subpopulations of excitatory pyramidal cells have been more elusive.
      An emerging new approach consists of transgenic mice that express fluorescent
      proteins under the control of promoters that are active in specific cell types.
      Here, we analyzed a line of transgenic mice that carries a transgene consisting
      of regulatory sequences of the potassium channel Kv3.1 and enhanced yellow
      fluorescent protein (EYFP). In these mice, a set of neurons in neocortical layer
      5 expresses high levels of the transgenic marker protein. EYFP-expressing, and
      nonexpressing layer 5 cells were easily identified in living tissue under
      conditions suitable for patch-clamp electrophysiology. By using immunolabeling,
      retrograde Fast Blue labeling and electrophysiological recordings with biocytin
      injections, we identified the fluorescent neurons as a population of pyramidal
      cells with distinct morphological and electrophysiological properties when
      compared with nonfluorescent neighboring layer 5 pyramidal cells. The most
      prominent morphological difference between these two populations was a much
      smaller number of apical oblique dendrites in EYFP-positive as compared with the
      EYFP-negative cells. The most prominent electrophysiological feature was a steady
      spike frequency adaptation in EYFP-positive cells, whereas EYFP-negative cells
      responded to a depolarizing current injection with a closely spaced spike doublet
      followed by constant frequency firing. The in vivo labeled transgenic mice
      provide an experimental tool for further functional differentiation of these
      populations of layer 5 pyramidal cells.

PMID- 15515025
TI  - Neurotransmitter properties of spinal interneurons in embryonic and larval
      zebrafish.
AB  - Many classes of spinal interneurons in zebrafish have been described based on
      morphology, but their transmitter phenotypes are largely unknown. Here we combine
      back-filling or genetic labeling of spinal interneurons with in situ staining for
      markers of neurotransmitter phenotypes, including the vesicular glutamate
      transporter (VGLUT) genes for glutamatergic neurons, the neuronal glycine
      transporter (GLYT2) for glycinergic neurons, and glutamic acid decarboxylase
      (GAD) for GABAergic neurons. Neurons positive for VGLUT include the commissural
      CoPA, MCoD, UCoD, and some of the CoSA neurons. The CiD interneurons, which have
      ipsilateral descending axons, were also VGLUT-positive, as were the ventrally
      located VeMe interneurons, whose descending axonal trajectory has not been
      clearly revealed. Cells positive for GLYT2 include the commissural CoLAs as well
      as some of the CoBL and CoSA neurons. The CiA cells were the only GLYT2-positive
      cells with an ipsilateral axon. Cells staining for GAD included, most notably,
      the dorsal longitudinal ascending (DoLA) and KA interneurons. Our approach
      allowed us to define the likely transmitter phenotypes of most of the known
      classes of spinal interneurons. These data provide a foundation for understanding
      the functional organization of the spinal networks in zebrafish.

PMID- 15515027
TI  - Comment: a biological guide for electromagnetic safety: the stress response.
AB  - Questions of safety of electromagnetic (EM) fields should be based on relevant
      biological properties, i.e., specific cellular reactions to potentially harmful
      stimuli. The stress response is a well documented protective reaction of plant
      and animal cells to a variety of environmental threats, and it is stimulated by
      both extremely low frequency (ELF) and radio frequency (RF) EM fields. It
      involves activation of DNA to initiate synthesis of stress proteins. Thermal and
      non-thermal stimuli affect different segments of DNA and utilize different
      biochemical pathways. However, both ELF and RF stimulate the same non-thermal
      pathway. Since the same biochemical reactions are stimulated in different
      frequency ranges with very different specific absorption rates (SARs), SAR level
      is not a valid basis for safety standards. Studies of EM field interactions with
      DNA and with model systems provide insight into a plausible mechanism that can be
      effective in ELF and RF ranges.

PMID- 15515028
TI  - Electroporation of a lipid bilayer as a chemical reaction.
AB  - When a cell's transmembrane potential is increased from a physiological one to
      more than 370 mV, the transmembrane current increases more than hundredfold
      within a millisecond. This is due to the formation of conductive pores in the
      membrane. We construct a model in which we conceive of pore formation as a
      voltage sensitive chemical reaction. The model predicts the logarithm of the pore
      formation rate to increase proportionally to the square of the voltage. We
      measure currents through frog muscle cell membranes under 8 ms pulses of up to
      440 mV. The experimental data appear consistent with the model.

PMID- 15515029
TI  - Effects of weak 16 3/2 Hz magnetic fields on growth parameters of young sunflower
      and wheat seedlings.
AB  - Previous studies on effects of magnetic fields on plants focussed on the power
      frequencies (50-60 Hz), but in Austria and Germany electric railways are powered
      by a frequency of 16 2/3) Hz. In the present study, sunflower and wheat seedlings
      were exposed to 16 2/3 Hz sinusoidal 20 muT (rms) vertical magnetic fields. Seeds
      were germinated in a germination roll and grown for 12 days under continued
      exposure. Seven series with sunflower and six series with wheat were done over 2
      years. Sunflower seedlings exposed to experimental magnetic field showed small,
      but significant increases in total fresh weights, shoot fresh weights, and root
      fresh weights, whereas dry weights and germination rates remained unaffected.
      Experimentally treated wheat exhibited marginally (but significantly) higher root
      fresh and dry weights, total fresh weights, and higher germination rates.

PMID- 15515030
TI  - Transmembrane voltage induced on altered erythrocyte shapes exposed to RF fields.
AB  - In this article, the transmembrane voltage induced on erythrocyte, codocyte,
      ovalocyte and spherocyte cell models exposed to a linearly polarised
      electromagnetic plane wave of frequency 1800 MHz is calculated. For this purpose,
      a finite element (FE) numerical technique with adaptive meshing is used. The
      results show that the value of the induced voltage on the original erythrocyte
      shape is higher than the one observed on the rest of the altered cell geometries
      studied. The erythrocyte shape and the membrane electric permittivity are shown
      to play a fundamental role on the values of the induced transmembrane voltage.

PMID- 15515031
TI  - Dopaminagonists and fibrotic valvular heart disease: further considerations.

PMID- 15515032
TI  - Evaluation of genotoxic effect of low level 50 Hz magnetic fields on human blood
      cells using different cytogenetic assays.
AB  - The question whether extremely low frequency magnetic fields (ELFMFs) may
      contribute to mutagenesis or carcinogenesis is of current interest. In order to
      evaluate the possible genotoxic effects of ELFMFs, human blood cells from four
      donors were exposed in vitro for 48 h to 50 Hz, 1 mT uniform magnetic field
      generated by a Helmholtz coil system. Comet assay (SCGE), sister chromatid
      exchanges (SCE), chromosome aberrations (CAs), and micronucleus (MN) test were
      used to assess the DNA damage. ELF pretreated cells were also irradiated with 1
      Gy of X-ray to investigate the possible combined effect of ELFMFs and ionizing
      radiation. Furthermore, nuclear division index (NDI) and proliferation index
      (PRI) were evaluated. Results do not evidence any DNA damage induced by ELFMF
      exposure or any effect on cell proliferation. Data obtained from the combined
      exposure to ELFMFs and ionizing radiation do not suggest any synergistic or
      antagonistic effect.

PMID- 15515033
TI  - Magnetic resonances of ions in biological systems.
AB  - A magnetic field transduction mechanism based on an ion oscillator model is
      derived from an explicit quantum mechanical description. The governing equation
      prescribes how the electric dipole moment of an ion oscillating in a symmetric
      potential well evolves under the influence of an arbitrary magnetic field. The
      resulting equation is an analog of the Bloch equation, a well-studied model for
      magnetic resonances in atomic and molecular spectroscopy. The differential
      equation for this ion oscillator model is solved numerically for a few
      illustrative magnetic field exposures, showing when those resonances occur with
      single frequency, linearly polarized fields. Our formulation makes explicit the
      conditions that must be present for magnetic fields to produce observable
      biological effects under the ion oscillator model. The ion's potential well must
      have symmetry sufficient to produce a degenerate excited state, e.g., octahedral
      or trigonal bipyramid potentials. The impulse that excites the ion must be
      spatially correlated with the orientation of the detector that reads off the
      final state of the oscillator. The orientation between the static and oscillating
      magnetic fields that produces resonance is a complicated function of the field
      magnitudes and frequency. We suggest several classes of experiments that could
      critically test the validity of the model presented here.

PMID- 15515034
TI  - Large scale in vitro experiment system for 2 GHz exposure.
AB  - A beam formed radiofrequency (RF) exposure-incubator employing a horn antenna, a
      dielectric lens, and a culture case in an anechoic chamber is developed for large
      scale in vitro studies. The combination of an open type RF exposure source and a
      culture case through which RF is transmitted realizes a uniform electric field
      (+/-1.5 dB) in a 300 x 300 mm area that accommodates 49 35 mm diameter culture
      dishes. This large culture dish area enables simultaneous RF exposure of a large
      number of cells or various cell lines. The RF exposure source operates at 2142.5
      MHz corresponding to the middle frequency of the downlink band of the
      International Mobile Telecommunication 2000 (IMT-2000) cellular system. The
      dielectric lens, which has a gain of 7 dB, focuses RF energy in the direction of
      the culture case and provides a uniform electric field. The culture case is
      sealed and connected to the main unit for environmental control, located outside
      the anechoic chamber, via ducts. The temperature at the center of the tray, which
      contains the culture dishes in the culture room, is maintained at 37.0 +/- 0.2
      degrees C by air circulation. In addition, the appropriate CO2 density and
      humidity supplied to the culture case realizes stable long-term culture
      conditions. Specific absorption rate (SAR) dosimetry is performed using an
      electric field measurement technique and the Finite Difference Time Domain (FDTD)
      calculation method. The results indicate that the mean SAR of the culture fluid
      at the bottom of the 49 (7 x 7 array) culture dishes used in the in vitro
      experiments is 0.175 W/kg for an antenna input power of 1 W and the standard
      deviation of the SAR distribution is 59%. When only 25 culture dishes (5 x 5
      array) are evaluated, the mean SAR is 0.139 W/kg for the same antenna input power
      and the standard deviation of the SAR distribution is 47%. The proliferation of
      the H4 cell line in 72 h in a pair of RF exposure-incubators reveals that the
      culture conditions are equivalent to those of a common CO2 incubator.

PMID- 15515035
TI  - The effect of weak 50 Hz magnetic fields on the number of free oxygen radicals in
      rat lymphocytes in vitro.
AB  - The aim of the work was verification of the hypothesis that weak power frequency
      (50 Hz) magnetic fields (MF) affected the number of free oxygen radicals in
      living biological cells and that these changes could be qualitatively explained
      by the radical pair mechanism. The experiments were performed on rat lymphocytes.
      One-hour exposure to 50 Hz MF at 20, 40, or 200 microT flux densities was
      performed inside a pair of Helmholtz coils with axis along or crosswise to the
      Earth's static MF. Iron ions (FeCl2) were used as a stimulator of the oxidation
      processes. Oxygen radicals were measured by fluorimetry using a DCF-DA
      fluorescent probe. Only in the lymphocytes exposed at 40 microT MF directed along
      the Earth's static MF there was a decrease of fluorescence in relation to non
      exposed samples. Our observation seems to confirm the hypothesis that low level
      power frequency MF affects oxidative processes which occur in living biological
      cells and that this effect can be explained by the radical pair mechanism.

PMID- 15515036
TI  - In vitro exposure apparatus for ELF magnetic fields.
AB  - For in vitro studies on the effect of extremely low frequency (ELF) magnetic
      field exposures in different laboratories, a programmable, high precision
      exposure system enabling blinded exposures has been developed and fully
      characterized. It is based on two shielded 4 coil systems that fit inside a
      commercial incubator. The volume of uniform B field exposure with 1% field
      tolerance is 50% larger compared to a Merrit 4 coil system with the same coil
      volume. The uncertainties for the applied magnetic fields have been specified to
      be less than 4%. The computer controlled apparatus allows signal waveforms that
      are composed of several harmonics, blind protocols, monitoring of exposure and
      environmental conditions and the application of B fields up to 3.6 mT root-mean
      square amplitude. Sources of artifacts have been characterized: sham isolation
      >43 dB, parasitic incident E fields <1 V/m, no recognizable temperature
      differences in the media for exposure or sham state, and vibrations of the
      mechanically decoupled dish holder <0.1 m/s(2) (= 0.01 g), which is only twice
      the sham acceleration background level produced by the incubator and fan
      vibrations.

PMID- 15515037
TI  - No influence of 20 and 400 microT, 50 Hz magnetic field exposure on cognitive
      function in humans.
AB  - The aim of the present study was to investigate cognitive effects of a
      continuous, vertical extremely low frequency (ELF) magnetic field (MF) of 20 and
      400 microT 50 Hz in healthy young men during performance on cognitive tests.
      Thirty-two volunteers (20-30 years old, mean 22.6 +/- 2.2 years) participated in
      this double blind study. The test protocol consisted of a set of tests: divided
      attention, flexibility, memory updating, digit span, digit span with articulary
      suppression, and time perception. The total duration of the exposure was 65 min.
      Participants were assigned four sessions: three conditions in the helmet (sham
      exposure, 20 and 400 microT) and one condition out of the helmet (to control the
      expectancy effect). No effect of MF exposure was observed on performance.

PMID- 15515038
TI  - Extremely low frequency-modulated static magnetic fields to treat cancer: A pilot
      study on patients with advanced neoplasm to assess safety and acute toxicity.
AB  - Results of a toxicity pilot human study approved by the competent ethical
      Committee are reported. Eleven patients with heavily pre-treated advanced cancer
      were enrolled in a pilot study with different schedules of time exposure to
      static magnetic fields (MF), amplitude modulated by ELF. An area including the
      neck, thoracic and abdomen was MF exposed daily, 5 days/week for 4 weeks
      according to two different schedules: 20 min daily (4 patients) and 70 min daily
      (7 patients). ECOG performance status was 1 (2 patients), 2 (8 patients), 3 (1
      patient). Toxicity was assessed according to WHO criteria. ECG, Chest X-ray,
      physical examination, blood cell count and complete blood chemistry were
      performed before and at the end of the treatment. Aspartate aminotransferase
      (AST) and alanine aminotransferase (ALT) elevation (grade 2 toxicity) in 1
      patient and microscopic urinary abnormalities in 5 patients were the only
      negative effects observed. We conclude that MF can be safely administrated
      according to the MF exposure schedules.

PMID- 15515039
TI  - Effects of a 60 Hz magnetic field on photosynthetic CO2 uptake and early growth
      of radish seedlings.
AB  - Photosynthetic CO2 uptake rate and early growth parameters of radish Raphanus
      sativus L. seedlings exposed to an extremely low frequency magnetic field (ELF
      MF) were investigated. Radish seedlings were exposed to a 60 Hz, 50 microT(rms)
      (root mean square) sinusoidal magnetic field (MF) and a parallel 48 microT static
      MF for 6 or 15 d immediately after germination. Control seedlings were exposed to
      the ambient MF but not the ELF MF. The CO2 uptake rate of ELF MF exposed
      seedlings on day 5 and later was lower than that of the control seedlings. The
      dry weight and the cotyledon area of ELF MF exposed seedlings on day 6 and the
      fresh weight, the dry weight and the leaf area of ELF MF exposed seedlings on day
      15 were significantly lower than those of the control seedlings, respectively. In
      another experiment, radish seedlings were grown without ELF MF exposure for 14 d
      immediately after germination, and then exposed to the ELF MF for about 2 h, and
      the photosynthetic CO2 uptake rate was measured during the short-term ELF MF
      exposure. The CO2 uptake rate of the same seedlings was subsequently measured in
      the ambient MF (control) without the ELF MF. There was no difference in the CO2
      uptake rate of seedlings exposed to the ELF MF or the ambient MF. These results
      indicate that continuous exposure to 60 Hz, 50 microT(rms) sinusoidal MF with a
      parallel 48 microT static MF affects the early growth of radish seedlings, but
      the effect is not so severe that modification of photosynthetic CO2 uptake can
      observed during short-term MF exposure.

PMID- 15515040
TI  - Birds have dinosaur wings: The molecular evidence.
AB  - Within developmental biology, the digits of the wing of birds are considered on
      embryological grounds to be digits 2, 3 and 4. In contrast, within paleontology,
      wing digits are named 1, 2, 3 as a result of phylogenetic analysis of fossil taxa
      indicating that birds descended from theropod dinosaurs that had lost digits 4
      and 5. It has been argued that the development of the wing does not support the
      conclusion that birds are theropods, and that birds must have descended from
      ancestors that had lost digits 1 and 5. Here we use highly conserved gene
      expression patterns in the developing limbs of mouse and chicken, including the
      chicken talpid(2)mutant and polydactylous Silkie breed (Silkie mutant), to aid
      the assessment of digital identity in the wing. Digit 1 in developing limbs does
      not express Hoxd12, but expresses Hoxd13. All other digits express both Hoxd12and
      Hoxd13. We found this signature expression pattern identifies the anteriormost
      digit of the wing as digit 1, in accordance with the hypothesis these digits are
      1, 2 and 3, as in theropod dinosaurs. Our evidence contradicts the long-standing
      argument that the development of the wing does not support the hypothesis that
      birds are living dinosaurs.

PMID- 15515041
TI  - Paternal and maternal influences on the psychological well-being, substance
      abuse, and delinquency of Chinese adolescents experiencing economic disadvantage.
AB  - On two occasions separated by one year, Chinese adolescents with economic
      disadvantage in Hong Kong (N = 199) responded to instruments measuring perceived
      parental parenthood qualities (indexed by perceived parenting styles, support and
      help from parents, and conflict and relationship with the parents) and
      psychosocial adjustment (psychological well-being, substance abuse, and
      delinquency). Results showed that parental parenthood variables were concurrently
      associated with different measures of adolescent psychological well-being and
      problem behavior at Time 1 and Time 2. While paternal parenthood qualities at
      Time 1 predicted changes in existential well-being and delinquency in adolescent
      boys, but not in adolescent girls, at Time 2, maternal parenthood qualities at
      Time 1 predicted changes in the mental health and problem behavior in adolescent
      girls, but not in adolescent boys, at Time 2. There is no strong support for the
      thesis that adolescent adjustment influences perceived parental parenthood
      qualities over time. The present study suggests that the influences of fathers
      and mothers on the adjustment of Chinese adolescents experiencing economic
      disadvantage vary with the gender of adolescent children.

PMID- 15515042
TI  - Mucoepidermoid carcinoma of the parotid gland in a child previously treated for
      acute lymphoblastic leukemia.
AB  - Occurrence of second cancers is a major concern for the care of children cured of
      cancer. Children treated for acute lymphoblastic leukemia (ALL) have an increased
      risk for developing mucoepidermoid carcinomas (MEC) of the parotid gland. The
      latent period ranges from 5 to 16 years. A 3-year-old boy presented with pre-B
      ALL. Treatment included multidrug chemotherapy and prophylactic intrathecal
      injections of methotrexate and prednisolone. Low-grade MEC of the left parotid
      gland was diagnosed at the age of 7 years, only 1 year after completing
      treatment. Local lymph nodes were not metastatic, and course was favorable 8
      years after complete surgical excision. This case report is remarkable for the
      early diagnosis of second cancer, only 4 years after diagnosis of ALL, and its
      occurrence in parotid gland without previous head and neck irradiation. It
      highlights the need for concern about second cancers of the parotid gland in
      children treated for ALL.

PMID- 15515043
TI  - Treatment of pediatric febrile neutropenia in the era of vancomycin-resistant
      microbes.
AB  - PURPOSE: The increasing frequency of Gm(+) infections in febrile neutropenic (FN)
      patients has resulted in increased use of vancomycin (VN). Likely as a result, VN
      resistant Enterococcus (VRE) has become a significant concern in FN patients. We
      sought to understand how the emergence of VN resistant microbes has changed the
      antibiotic management of pediatric FN. METHODS: A questionnaire was distributed
      by e-mail to responsible investigators of the Children's Oncology Group. RESULTS:
      One hundred and thirty responses were analyzed. Forty-four percent initially used
      monotherapy, with 82% of those using ceftazidime. Twenty-seven used VN with
      another agent, generally ceftazidime. After the emergence of VRE and VN-resistant
      staphylococcus (VRS), monotherapy increased to 58%. Ceftazidime continued to be
      most frequently used. There was a 57% reduction in the use of VN with 88% of
      centers not currently using VN in their initial treatment of FN. Forty-seven
      percent of the centers that continue to use VN have VRE, while 90% that have
      discontinued its use have VRE/VRS. CONCLUSIONS: Ours is the first study to survey
      current practices in the treatment of pediatric FN and to document changes in
      practice patterns due to emerging antibiotic resistance patterns. We demonstrate
      increased use of monotherapy for FN, and a 57% decrease in the use of VN. Local
      considerations influence antibiotic choices with a significant difference in VRE
      prevalence between those centers that continue to use VN as compared to those
      that have discontinued it.

PMID- 15515044
TI  - Early molecular detection of central nervous system relapse in a child with
      systemic anaplastic large cell lymphoma: case report and review of the
      literature.
AB  - We report a case of anaplastic large cell lymphoma (ALCL) with central nervous
      system relapse in an 11-year-old boy. The relapse was suspected on morphologic
      examination of the cytospin preparations of the cerebrospinal fluid (CSF) with a
      WBC of 10 cells/microl. CSF relapse was confirmed using immunohistochemistry
      (IHC), fluorescence in situ hybridization (FISH), and reverse transcriptase
      polymerase chain reaction (RT-PCR) for abnormal ALK expression or gene structure.
      The patient developed large intracranial metastases, despite systemic, and
      intrathecal chemotherapy. This case demonstrates the feasibility of detecting
      ALCL in paucicellular CSF specimens and suggests that even low CSF involvement
      can herald massive parenchymal disease.

PMID- 15515045
TI  - Synthesis and HPLC enantioseparation of the cyclopropane analogue of valine
      (c3Val).
AB  - A new and efficient method is presented for the preparation of the N-Boc
      protected cyclopropane analogue of valine, 1-(N-tert-butoxycarbonyl)amino-2,2
      dimethylcyclopropanecarboxylic acid, both in racemic and enantiomerically pure
      forms. Cyclopropanation of the exocyclic double bond of 2-phenyl-4-isopropylidene
      5(4H)-oxazolone with diazomethane followed by elaboration of the heterocyclic
      moiety provided multigram quantities of the racemic target compound. Subsequent
      HPLC resolution of a racemic precursor on a noncommercial chiral stationary phase
      has given access to enantiomerically pure products. Almost 1.5 g of the first
      eluted enantiomer and 1.0 g of the second-eluted enantiomer have been isolated in
      optically pure form using a 150 x 20 mm ID column containing mixed 10
      undecenoate/3,5-dimethylphenylcarbamate of cellulose covalently bonded to
      allylsilica gel with a mixture of hexanes/tert-butyl methyl ether/ethyl acetate
      as the mobile phase.

PMID- 15515046
TI  - Application of lipases in kinetic resolution of racemates.
AB  - Lipases have been well established as valuable catalysts in organic synthesis.
      This review article focuses on some of the recent developments in the rapidly
      growing field of lipase-catalyzed kinetic resolution of racemates as a versatile
      method for the separation of enantiomers. The literature search dates back to the
      last five years and covers some comprehensive examples. The main emphasis is on
      the use of lipases in organic solvents.

PMID- 15515047
TI  - Kinetic resolution of ibuprofen catalyzed by Candida rugosa lipase in ionic
      liquids.
AB  - Candida rugosa lipase-catalyzed esterification of ibuprofen with 1-propanol was
      conducted in seven ionic liquids and the results were compared with those in
      isooctane. Although the enzyme showed comparable or higher activity in some ionic
      liquids compared to that in isooctane, only in the case of [BMIM]PF6 was the
      enantioselectivity (E = 24.1) almost twice that (E = 13.0) of isooctane. In
      another six ionic liquids the enzyme enantioselectivity was much poorer (E = 1.1
      6.4). At the same conversion of 30%, E of [BMIM]PF6 is more than triple that of
      isooctane. The lipase stability in [BMIM]PF6 was improved by 25% of that in
      isooctane. It was concluded that [BMIM]PF6 could be applied to substitute the
      conventional organic solvent (isooctane) in the esterification of ibuprofen.

PMID- 15515048
TI  - Neuroimmunoprotective effects of estrogen and derivatives in experimental
      autoimmune encephalomyelitis: therapeutic implications for multiple sclerosis.
AB  - The extensive literature and the work from our laboratory illustrate the large
      number of complex processes affected by estrogen that might contribute to the
      striking ability of 17beta-estradiol (E2) and its derivatives to inhibit clinical
      and histological signs of experimental autoimmune encephalomyelitis (EAE) in
      mice. These effects require sustained exposure to relatively low doses of
      exogenous hormone and offer better protection when initiated prior to induction
      of EAE. However, oral ethinyl estradiol (EE) and fluasterone, which lacks
      estrogenic side effects, could partially reverse clinical EAE when given after
      the onset of disease. The three main areas discussed in this review include E2
      mediated inhibition of encephalitogenic T cells, inhibition of cell migration
      into central nervous system tissue, and neuroprotective effects that promote axon
      and myelin survival. E2 effects on EAE were mediated through Esr1 (alpha receptor
      for E2) but not Esr2 (beta receptor for E2), as were its antiinflammatory and
      neuroprotective effects. A novel finding is that E2 up-regulated the expression
      of Foxp3 and CTLA-4 that contribute to the activity of CD4+CD25+ Treg cells. The
      protective effects of E2 in EAE suggest its use as therapy for MS, although the
      risk of cardiovascular disease may complicate treatment in postmenopausal women.
      This risk could be minimized by using subpregnancy levels of exogenous E2 that
      produced synergistic effects when used in combination another immunoregulatory
      therapy. Alternatively, one might envision using EE or fluasterone metabolites
      alone or in combination therapies in both male and female MS patients.

PMID- 15515049
TI  - Expression of urokinase plasminogen activator, its receptor and type-1 inhibitor
      in malignant and benign prostate tissue.
AB  - The plasminogen activation (PA) cascade participates in degradation of
      extracellular matrix during cancer invasion. We have studied the expression of
      urokinase-type plasminogen activator (uPA) mRNA, uPA receptor (uPAR) mRNA and
      immunoreactivity, and type-1 plasminogen activator inhibitor (PAI-1) mRNA and
      immunoreactivity in 16 prostate adenocarcinomas and 9 benign prostate
      hyperplasias. uPA mRNA and uPAR mRNA expression were found in 9 and 8 of the
      adenocarcinomas, respectively, and in 7 and 6 of the benign hyperplasias,
      respectively. In both malignant and benign lesions, expression of these 2 mRNAs
      was predominantly seen in cells identified as macrophages, which in most of the
      carcinomas (approximately 90%) were located in the interstitial tissue between
      the tumor cell islands, while in most of the benign hyperplasias they were
      located in the lumen of the glands and were in only a few cases (approximately
      30%) found in the interstitial tissue. uPAR immunoreactivity correlated with the
      mRNA expression and was, in addition, found in neutrophils. PAI-1 mRNA was
      detected in 13 of the 16 carcinomas and in 8 of the 9 benign hyperplasias,
      located in scattered fibroblast-like cells in both groups, in some vascular
      structures and in a few macrophages located in the interstitial tissue of both
      malignant and benign lesions. A similar expression pattern was found for PAI-1
      immunoreactivity. In 8 of the 16 carcinomas, all 3 components were present, and
      in several areas colocalization was observed in stromal cells in close proximity
      to cancer cell islands. No immunoreactivity and/or mRNA expression of uPA, uPAR
      or PAI-1 was observed in cancer cells or in other epithelial cells in any of the
      cases.

PMID- 15515050
TI  - Morphological abnormalities in the spermatozoa of fertile and infertile men.
AB  - The morphological analysis of the spermatozoa from fertile and infertile men was
      performed using light and electron microscopy to clarify the relationship between
      sperm morphology and fertility. Semen samples obtained from 22 partners of
      pregnant women were prepared according to the protocol standardized in an
      international collaborative study. Semen samples from 17 patients with
      asthenozoospermia or varicocele were collected in a hospital. Abnormalities in
      the spermatozoa were classified into three types for the tails, two for the
      midpieces, and six for the heads according to the criteria adapted from WHO
      guidelines (World Health Organization, 1999: WHO laboratory manual for the
      examination of human semen and semen-cervical mucus interaction (4th edition)).
      Approximately 14% of the spermatozoa from the fertile men had abnormal tails at
      the light microscopic level while approximately 44% had abnormal heads. Most
      types of abnormalities found in the spermatozoa from the asthenozoospermic and
      varicocele patients were encountered in those from the fertile men, although the
      semen from the fertile men contained a higher percentage of normal spermatozoa
      than that from the patients. These results were also confirmed at the
      ultrastructural level. Most abnormal cell types are encountered in semen from
      fertile men, although the incidence of abnormalities is low.

PMID- 15515051
TI  - Status of RNAs, localized in Xenopus laevis oocytes, in the frogs Rana pipiens
      and Eleutherodactylus coqui.
AB  - Early development in the frog model, Xenopus laevis, is governed by RNAs,
      localized to the vegetal cortex of the oocyte. These RNAs include Xdazl RNA,
      which is involved in primordial germ cell formation, and VegT RNA, which
      specifies the mesoderm and endoderm. In order to determine whether orthologues of
      these RNAs are localized and have similar functions in other frogs, we cloned
      RpDazl and RpVegT from Rana pipiens, a frog that is phylogenetically distant from
      X. laevis. RNAs from both genes are localized to the vegetal cortex of the R.
      pipiens oocyte, indicating that the vegetal localization is likely the basal
      state. The animal location of EcVegT RNA in Eleutherodactylus coqui that we found
      previously (Beckham et al., 2003) is then a derived state, probably due to the
      great increase in egg size required for direct development of this species. To
      answer the question of function, we injected RpVegT or EcVegT RNAs into X. laevis
      embryos, and assayed animal caps for gene expression. Both of these RNAs induced
      the expression of endodermal, mesodermal, and organizer genes, showing that the
      function of RpVegT and EcVegT as meso-endodermal determinants is conserved in
      frogs. The RNA localizations and the function of VegT orthologues in germ layer
      specification may be synapomorphies for anuran amphibians.

PMID- 15515052
TI  - Structural and molecular characterization of equine sperm-binding fibronectin-II
      module proteins.
AB  - Phospholipid-binding proteins in the male genital tract are characterized by
      differing numbers Fn-2 modules (B-domain) carrying N-terminal extensions (A
      domain) of variable length. In the stallion, three different proteins were
      identified, SP-1, SP-2, and EQ-12. SP-1 and SP-2 of the AA'BB'- and ABB'-type,
      respectively, are major proteins of the seminal plasma. Here we report the cDNA
      sequences of SP-1, and of a new member of the SP-2 family (SPnew) and the partial
      characterization of their iso- and glycoforms. The phosphorylcholine (PC)-binding
      ability of the long Fn-2 protein, EQ-12, with four tandemly arranged Fn-2 modules
      was determined by PC-affinity chromatography. Expression patterns of EQ-12, and
      the SP-proteins were studied by means of RT-PCR, Northern blot analysis and
      immunological approaches indicating differential expression along the male
      reproductive tract. The vast majority of the short SP-1 and SP-2 proteins are
      produced by the ampulla whereas EQ-12 originates from the epididymis. Indirect
      immunofluorescence microscopy of sperm isolated from different regions of the
      epididymis and Western blot analysis indicate that both, the long and the short
      Fn-2 proteins associate to the sperm surface during post-testicular maturation.
      Sperm binding of Fn-2 proteins at the post-acrosome and midpiece was at first
      detected in the corpus epididymis. Enhanced fluorescence intensity after
      ejaculation point to an increased number of molecules bound to the sperm surface.
      The function of these proteins is discussed in regard to their structure-function
      relationships.

PMID- 15515053
TI  - Simultaneous activation of PLA2 and PLC are required to promote acrosomal
      reaction stimulated by progesterone via G-proteins.
AB  - The acrosome reaction (AR) is a special exocytotic process promoted by signal
      transduction pathways studied in many laboratories. Progesterone (P4) is one of
      the trigger molecules proposed. Upon the binding of P4 to its receptor, several
      molecules could be activated, including G-proteins, phospholipase A(2) (PLA(2)),
      and phospholipase C (PLC). The role of these molecules was analyzed in this study
      using the Chlortetracycline (CTC) protocol to detect and quantify the AR.
      Incubation of capacitated sperm cells with GTPgammas (GTPgammas, a mimetic of G
      protein activation), arachidonic acid (AA, product of PLA(2) action), or phorbol
      ester (PMA, an activator of PLC) for 15 min increased the AR to a similar
      percentage as P4. Conversely, a decrease in the AR was detected when sperm cells
      were incubated with P4 after preincubation with: GDPbetaS (GDP, an inhibitor of G
      protein activation), ONO RS-82 (ONO, an inhibitor of PLA(2)), or neomycin (Neo,
      an inhibitor of PLC) for 15 min. To analyze the activation sequence of G
      proteins, PLA(2), and PLC combinations of these mimetic/inhibitors were used
      during successive incubation periods. Inhibition promoted by GDP, ONO, and Neo
      were overcome by 15-min incubation with GTPgammas, AA, or PMA, respectively. But
      GTPgammas or P4 did not reverse the inhibition due to incubation with Neo and
      ONO. Interestingly, this dual inhibition was reverted by another 15-min
      incubation with AA or PMA. Results presented here could indicate that the AR
      triggered by P4 is driven by activation of G-proteins, that in turn activate
      PLA(2) and PLC simultaneously, that finally promote acrosomal exocytosis.

PMID- 15515054
TI  - Detection and expression of hepatitis B virus X gene in one and two-cell embryos
      from golden hamster oocytes in vitro fertilized with human spermatozoa carrying
      HBV DNA.
AB  - The main objectives of this study were to introduce motile human sperm carrying
      Hepatitis B virus (HBV) DNA to golden hamster oocytes in a co-culture environment
      and to detect the replication and expression of the HBx gene in early embryonic
      cells. Zona-free hamster oocytes were inseminated with human sperm carrying
      pBR322-HBV DNA plasmid using the in vitro fertilization (IVF) technique. Both the
      one- and two-cell stages of early embryonic development were studied. PCR, RT
      PCR, and Dot hybridization were performed to observe the HBx gene and its
      expression in these stages. "Fluorescence in situ hybridization" (FISH) was
      carried out to confirm the integration of HBV into the pronucleus, nucleus, and
      the chromosomes of embryos. The results showed that we have the ability to obtain
      a fertilization rate of 80%. RT-PCR showed that the HBx gene could be expressed
      in both one- and two-cell stages of embryonic development. The data suggested the
      possibility of sperm as a vector for the vertical transmission of HBV DNA to the
      next generation.

PMID- 15515055
TI  - Oxygen-regulated expression of GLUT-1, GLUT-3, and VEGF in the mouse blastocyst.
AB  - The oxygen concentration used in the incubation atmosphere during embryo culture
      influences embryo development rates and embryo quality. In somatic cells, oxygen
      levels can influence the expression of a range of genes, including glucose
      transporters, glycolytic enzymes, and angiogenic growth factors. Many of these
      oxygen-regulated genes have important roles in embryonic development and
      metabolism. The aim of this study was to determine whether oxygen regulates gene
      expression in the preimplantation mouse blastocyst. Mouse embryos were cultured
      from the 1-cell to morula stage under 7% oxygen, followed by culture under 20, 7,
      or 2% oxygen to the blastocyst stage. Expression of glucose transporter (GLUT)-1,
      GLUT-3, and vascular endothelial growth factor (VEGF) in blastocysts was measured
      by real-time reverse transcription PCR. Development from morula to blastocyst was
      not altered by culture under different oxygen conditions. Expression of GLUT-1,
      GLUT-3, and vascular endothelial growth (VEGF) was increased by 2- to 4-fold in
      embryos cultured under 2% oxygen, when compared to embryos cultured under 20 or
      7% oxygen, and when compared to embryos developed in vivo (all P < 0.001). These
      results suggest that the preimplantation mouse embryo has the capacity to detect
      and respond to low oxygen availability with changes in expression of oxygen
      regulated genes.

PMID- 15515056
TI  - Expression of growth differentiation factor 9 (GDF9), bone morphogenetic protein
      15 (BMP15), and BMP receptors in the ovaries of goats.
AB  - The process of ovarian folliculogenesis is composed of proliferation and
      differentiation of the constitutive cells in developing follicles. In goats,
      relatively little information is available on the local factors that regulate
      this process. We studied the presence and distribution of growth differentiation
      factor 9 (GDF9), bone morphogenetic protein 15 (BMP15), and BMP receptors types 2
      (BMPR2), 1A (BMPR1A), and 1B (BMPR1B) in goat ovaries to find evidence for their
      possible roles in folliculogenesis. Ovaries of cyclic goats were collected and
      fixed in paraformaldehyde for immunohistochemical localization of GDF9 and BMP15
      proteins or used to collect follicles and luteal tissue to study the mRNA
      expression of GDF9, BMP15, and BMP receptors using reverse transcriptase
      polymerase chain reaction (RT-PCR). GDF9 and BMP15 proteins were found in oocytes
      of all types of follicles and granulosa cells of primary, secondary, and antral
      but not primordial follicles. The mRNAs for GDF9, BMP15, BMPR2, BMPR1A, and
      BMPR1B were detected in primordial, primary, and secondary follicles as well as
      in oocyte and granulosa cells of antral follicles. Transcripts for BMPR2, BMPR1A,
      BMPR1B, and GDF9, and GDF9 protein were furthermore found in corpora lutea. It is
      concluded that the mRNAs and proteins of GDF9 and BMP15 and the mRNAs of BMP
      receptors are expressed in goat ovarian follicles at all stages of their
      development, and that they form a complex intrafollicular regulatory system
      during folliculogenesis. Expression of all BMP receptor mRNAs and GDF9 mRNA and
      protein in luteal tissue additionally points to a role of GDF9 in corpus luteum
      function.

PMID- 15515057
TI  - Mouse epiblasts change responsiveness to BMP4 signal required for PGC formation
      through functions of extraembryonic ectoderm.
AB  - Mouse primordial germ cells (PGCs) are initially identified as a cluster of
      alkaline phosphatase (AP)-positive cells within the extraembryonic mesoderm near
      the posterior part of the primitive streak at embryonic day (E) 7.25. Clonal
      analysis of epiblast cells has revealed that the putative precursors of PGCs are
      localized in the proximal epiblast, and we demonstrated that the conditions
      required for PGC formation are induced in the proximal region of epiblasts by
      extraembryonic ectoderm. Bone morphogenetic protein (BMP) 4 and BMP8b, which
      belong to the transforming growth factor-beta (TGF-beta) superfamily, might
      generate induction signals from extraembryonic ectoderm. Smad1 and Smad5, which
      are intracellular signaling molecules for BMP4, might also play a critical role
      in stimulating epiblasts to form PGC. However, how pluripotential epiblasts
      temporally and spatially respond to BMP signals to form PGCs remains unclear. The
      present study examines changes of responsiveness to BMP4 for PGC formation in
      epiblasts and their molecular mechanisms. We initially examined the effect of
      recombinant human (rh) BMP4 upon cultured epiblasts at different developmental
      stages, and found that they acquire the ability to respond to BMP4 signals for
      PGC formation between E5.25 and E5.5. In addition, such competence was conferred
      upon epiblasts by the extraembryonic ectoderm. We also showed that the increased
      expression of Smad1 and the onset of Smad5 expression induced by extraembryonic
      ectoderm might be responsible for quick acquisition of this competence.
      Furthermore, we show that only proximal epiblast cells maintain responsiveness to
      BMP4 for PGC formation at E6.0, and that this is associated with the proximal
      epiblast-specific expression of Smad5. These results explain why only the
      proximal region of epiblasts can sustain the ability to form PGCs.

PMID- 15515058
TI  - Germinal vesicle breakdown is not fully dependent on MAPK activation in maturing
      oocytes of marine nemertean worms.
AB  - Previously, it has been shown that oocytes of marine nemertean worms resume
      meiosis and undergo germinal vesicle breakdown (GVBD) following treatment with
      either natural seawater (NSW), or the neurohormone serotonin (5-hydroxytryptamine
      or 5-HT). In this investigation of the nemerteans Cerebratulus lacteus and
      Cerebratulus sp., immunoblots and kinase assays were used to compare the roles of
      two regulatory kinases: mitogen-activated protein kinase (MAPK) and Cdc2/cyclin B
      (referred to as maturation promoting factor or MPF). Based on such analyses, an
      ERK (extracellular signal regulated kinase) type of MAPK was found to be
      activated concurrently with Cdc2/cyclin B during NSW- and 5-HT-induced
      maturation. MAPK activation occurred prior to GVBD and seemed to be controlled
      primarily by phosphorylation rather than de novo protein synthesis. Inhibition of
      MAPK signaling by U0126 was capable of delaying but not permanently blocking
      Cdc2/cyclin B activation and GVBD in 5-HT treated oocytes and subsets of NSW
      treated oocytes. Collectively such data indicated that GVBD is not fully
      dependent on MAPK activation, since Cdc2/cyclin B can apparently be activated by
      MAPK-independent mechanism(s) in maturing nemertean oocytes.

PMID- 15515059
TI  - C-kit receptor and its possible function in human spermatozoa.
AB  - The presence and role of the c-kit proto-oncogene protein was investigated in the
      mature sperm of the human. A polyclonal antibody against the c-kit peptide was
      used to perform immunohistochemical (IHC) staining, electron microscopy (EM)
      studies, and Western blot analysis. The acrosomal region of fresh sperm
      specifically stained with the antibody. No acrosomal staining or staining limited
      to the equatorial region was noted in the acrosome-reacted (AR) sperm. EM studies
      demonstrated immunogold label on the plasma membrane (PM) of the acrosome, and
      confirmed the lack of binding following the acrosome reaction. A 150 kDa band was
      detected by Western blot analysis. This protein was released from the sperm
      surface during sperm capacitation and the acrosome reaction. Antibody against the
      c-kit receptor significantly inhibited the acrosome reaction and increased sperm
      agglutination, but did not significantly inhibit sperm motility. These results
      suggest that the c-kit receptor protein is present in mature human sperm and is
      released during capacitation and/or the acrosome reaction. The assessment of the
      c-kit receptor may also be a useful assay for sperm function in male infertility.

PMID- 15515060
TI  - Timing of MAP kinase inactivation effects on emission of polar body in porcine
      oocytes activated by Ca2+ ionophore.
AB  - Artificial activation is required for successful intracytoplasmic sperm injection
      (ICSI) to induce haploidy pronuclear formation with extraction of second polar
      body. The present study showed that an additional treatment with Phorbol 12
      myristate 13-acetate (PMA) followed by Ca(2+) ionophore treatment improved the
      rate of pronuclear formation, however, these oocytes had more than two pronuclei
      because of the suppression of polar body emission. The cultivation with MEK
      inhibitor U0126 followed by Ca(2+) ionophore also increased the rate of
      pronuclear formation but suppressed the emission of second polar body. These
      results suggested that the decrease of MAP kinase activity at early stage of
      artificial activation, concomitantly with decreasing p34(cdc2) kinase activity,
      prevented the second polar body extraction. We investigated that the timing of
      MAP kinase inactivation affected the extraction of the polar body and pronuclear
      formation rate. The addition of PMA 8 hr after Ca(2+) ionophore treatment induced
      the delay of MAP kinase inactivation, which resulted in haploidy pronuclear
      formation with emission of polar body. These results demonstrated for the first
      time that the delay of MAP kinase inactivation induced by PMA improved pronuclear
      formation with the extraction of second polar body in porcine oocytes activated
      by Ca(2+) ionophore. This method can be available for successfully ICSI in low
      response species of oocyte activation to Ca(2+) ionophore including pig.

PMID- 15515061
TI  - Anti-apoptotic action of stem cell factor on oocytes in primordial follicles and
      its signal transduction.
AB  - Stem cell factor (SCF) is essential for the development of primordial follicles.
      One of its functions is to prevent oocytes from apoptosis. However, the
      underlying mechanism remains largely unknown. By using cultured ovaries that are
      rich in primordial follicles, the anti-apoptotic action of SCF and the potential
      signal transduction pathways were investigated. The apoptosis was evaluated by
      means of in situ 3'-end labeling. The expressions of proteins were analyzed with
      immunohistochemistry and Western blot. The data showed that SCF significantly
      prevented oocytes from apoptosis in the cultured organs. Addition of a specific
      pharmacological inhibitor of PI3K abolished the anti-apoptotic action of SCF
      while that of a MEK inhibitor did not. The phosphorylation of two mitogen
      activated protein kinases (MAPKs) (p42 and p44) and AKT, the respective
      substrates of MEK and PI3K, were enhanced by SCF treatment. Not surprisingly, the
      MAPK activation occurred only in theca cells. The expressions of apoptosis
      related gene products, the Bcl-2 family proteins, in response to SCF treatment
      were also investigated. While SCF up-regulated the expression of the anti
      apoptotic proteins Bcl-2 and Bcl-xL, it did the opposite to the pro-apoptotic
      factor Bax. The PI3K inhibitor reversed the regulation of SCF on Bcl-xL and Bax
      but not on Bcl-2. Therefore, it seemed that SCF initiated an anti-apoptotic
      signal starting from its membrane receptor c-kit to Bcl-2 family members through
      PI3K/AKT and other signaling cascades in the oocytes of primordial follicles.

PMID- 15515063
TI  - Nuclearity controlled cyanide-bridged bimetallic CrIII-MnII compounds: synthesis,
      crystal structures, magnetic properties and theoretical calculations.
AB  - The preparation, X-ray crystallography and magnetic investigation of the
      compounds PPh4[Cr(bipy)(CN)4].2 CH3CN.H2O (1) (mononuclear), [[Cr(bipy)(CN)4]2Mn
      (H2O)4].4H2O (2) (trinuclear), [[Cr(bipy)(CN)4]2Mn(H2O)2] (3) (chain) and
      [[Cr(bipy)(CN)4]2Mn(H2O)].H2O.CH3CN (4) (double chain) [bipy=2,2'-bipyridine;
      PPh4 (+)=tetraphenylphosphonium] are described herein. The [Cr(bipy)(CN)4]- unit
      act either as a monodentate (2) or bis-monodentate (3) ligand toward the
      manganese atom through one (2) or two (3) of its four cyanide groups. The
      manganese atom is six-coordinate with two (2) or four (3) cyanide nitrogens and
      four (2) or two (3) water molecules building a distorted octahedral environment.
      In 4, two chains of 3 are pillared through interchain Mn-N-C-Cr links which
      replace one of the two trans-coordinated water molecules at the manganese atom to
      afford a double chain structure where bis- and tris-monodenate coordination modes
      of [Cr(bipy)(CN)4]- coexist. The magnetic properties of 1-4 were investigated in
      the temperature range 1.9-300 K. A Curie law behaviour for a magnetically
      isolated spin quartet is observed for 1. A significant antiferromagnetic
      interaction between CrIII and MnII through the single cyanide bridge [J=-6.2 cm(
      1), the Hamiltonian being defined as H=-J(SCr1.SMn+SCr2.SMn] occurs in 2 leading
      to a low-lying spin doublet which is fully populated at T <5 K. A metamagnetic
      behaviour is observed for 3 and 4 [the values of the critical field Hc being ca.
      3000 (3) and 1500 Oe (4)] which is associated to the occurrence of weak
      interchain antiferromagnetic interactions between ferrimagnetic Cr2III MnII
      chains. The analysis of the exchange pathways in 2-4 through DFT type
      calculations together with the magnetic bevaviour simulation using the quantum
      Monte Carlo methodology provided a good understanding of their magnetic
      properties.

PMID- 15515062
TI  - TESSP-1: a novel serine protease gene expressed in the spermatogonia and
      spermatocytes of adult mouse testes.
AB  - A cDNA encoding a novel type of serine protease, designated testis-specific
      serine protease 1 (TESSP-1), was cloned using mRNA isolated from the adult mouse
      testis. The open reading frame of this cDNA codes for a protein of 322 amino
      acids, which includes a hydrophobic signal peptide of 18 amino acids and an N
      terminal activation peptide of 34 amino acids. The protein has an additional
      hydrophobic amino acid sequence at the C-terminus. Expression of the TESSP-1 gene
      was restricted to the testis. TESSP-1 mRNA expression initiated in the mouse
      testis at 2 weeks after birth, and its level increased steadily with sexual
      maturation of the animal. In situ hybridization analysis revealed that TESSP-1
      mRNA was expressed in type B spermatogonia and spermatocytes at stages between
      preleptotene and pachytene. The testis contained at least five distinct forms of
      TESSP-1 transcript, which presumably resulted from alternative splicing of the
      mRNA, but only one of these transcripts encodes a complete, functional enzyme.
      Expression experiments using COS-7 cells showed that TESSP-1 was synthesized as a
      glycoprotein with N-glycosylated carbohydrates. Tests also showed that the C
      terminal hydrophobic region of TESSP-1 was important upon its binding to the
      membrane by anchoring through glycosylphosphatidylinositol (GPI).

PMID- 15515064
TI  - High-throughput heterogeneous catalytic science.
AB  - High-throughput experimentation in heterogeneous catalysis has recently
      experienced nearly exponential growth. Initial qualitative screening has evolved
      into quantitative high-throughput experimentation, characterization, and
      analysis. This allows high-throughput catalysis now to rise above simple
      screening to the level of fundamental understanding of reaction mechanisms, which
      will lead on a faster path to the Holy Grail of catalysis: rational catalyst
      design.

PMID- 15515065
TI  - A modular approach to DNA-programmed self-assembly of macromolecular
      nanostructures.
AB  - DNA-programmed organic reactions are new and powerful tools for assembling
      chemical compounds into predetermined complex structures and a brief review of
      their use is given. This approach is particular efficient for the selection and
      covalent coupling of multiple components. DNA-templated synthesis is used for
      polymerization of PNA tetramers and for copying of the connectivity information
      in DNA. Direct DNA-programmed multicomponent coupling of custom designed organic
      modules is described. The macromolecular structures obtained are highly
      conjugated potentially conducting nanoscaffolds. Some future developments in this
      area are discussed.

PMID- 15515066
TI  - Supported ionic liquid catalysis.
AB  - Supported ionic liquid catalysis is a concept which combines the advantages of
      ionic liquids with those of heterogeneous support materials. The viability of
      this concept has been confirmed by several studies which have successfully
      confined various ionic phases to the surface of support materials and explored
      their potential catalytic applications. Although the majority of the evaluated
      supports were silica based, several studies focused on polymeric materials
      including membranes. The preparation of these materials was achieved by using two
      different immobilization approaches. The first approach involves the covalent
      attachment of ionic liquids to the support surface whereas the second simply
      deposits the ionic liquid phases containing catalytically active species on the
      surface of the support. Herein recent advances made in this area are described.

PMID- 15515067
TI  - A practical synthesis of (+)-biotin from L-cysteine.
AB  - Alpha-amino aldehyde 4, which is readily derived from L-cysteine through
      cyclization and elaboration of the carboxy group, was subjected to the Strecker
      reaction, which, via sodium bisulfite adduct 16, afforded alpha-amino nitrile 5
      with high diastereoselectivity (syn/anti=11:1) and in high yield. Amide 6,
      derived from 5, was converted to thiolactone 8, a key intermediate in the
      synthesis of (+)-biotin (1), by a novel S,N-carbonyl migration and cyclization
      reaction. The Fukuyama coupling reaction of 8 with the zinc reagent 21, which has
      an ester group, in the presence of a heterogeneous Pd/C catalyst allowed the
      efficient installation of the 4-carboxybutyl chain to provide 9. Compound 9 was
      hydrogenated and the protecting groups removed to furnish 1 in 10 steps and in 34
      % overall yield from L-cysteine.

PMID- 15515068
TI  - Kinetic study of phosphorylation-dependent complex formation between the kinase
      inducible domain (KID) of CREB and the KIX domain of CBP on a quartz crystal
      microbalance.
AB  - We report quantitative analysis of peptide-peptide interactions on a 27 MHz
      quartz crystal microbalance (QCM) in aqueous solution. The KID (kinase-inducible
      domain) of transcription factor CREB (cyclic AMP response element binding
      protein) is known to interact with the KIX domain of coactivator CBP (CREB
      binding protein), facilitated by phosphorylation at Ser-133 of the KID. The KIX
      domain peptide (86 aa) was immobilized on the QCM gold electrode surface by means
      of a poly(ethylene glycol) spacer. Binding of the KID peptide (46 aa) to the KIX
      peptide was detected by frequency decreases (mass increases) of the QCM. Both
      maximum binding amount (Deltammax) and association constants (Ka) obtained from
      the QCM measurements increased as a result of phosphorylation of Ser-133 of the
      KID peptide. The Ka values for KIX peptide to the phosphorylated (pKID) and
      unphosphorylated KID peptides were (93+/-2) x 10(3) and (5+/-1) x 10(3) M(-1),
      respectively. This difference was explained by the dissociation rate constant (k(
      1)) of the pKID being 20 times smaller than that of the KID, while association
      rate constants (k1) were independent of phosphorylation.

PMID- 15515069
TI  - Bulky monodentate phosphoramidites in palladium-catalyzed allylic alkylation
      reactions: aspects of regioselectivity and enantioselectivity.
AB  - A series of bulky monodentate phosphoramidite ligands, based on biphenol, BINOL
      and TADDOL backbones, have been employed in the Pd-catalysed allylic alkylation
      reaction. Reaction of disodium diethyl 2-methyl malonate with monosubstituted
      allylic substrates in the presence of palladium complexes of the phosphoramidite
      ligands proceeds smoothly at room temperature. The regioselectivities observed
      depend strongly on the leaving group and the geometry of the allylic starting
      compounds. Mono-coordination occurs when these ligands are ligated in
      [Pd(allyl)(X)] complexes (allyl=C3H5, 1-CH3C3H4, 1-C6H5C3H4, 1,3-(C6H5)2C3H3;
      X=Cl, OAc). The solid-state structure determined by X-ray diffraction of
      [Pd(C3H5)(1)(Cl)] reveals a non-symmetric coordination of the allyl moiety,
      caused by the stronger trans influence of the phosphoramidite ligand relative to
      X-. In all of these complexes, the syn,trans isomer is the major species present
      in solution. Because of fast isomerisation and high reactivity of the syn,cis
      complex, the major product formed upon alkylation is the linear product,
      especially for monosubstituted phenylallyl substrates in the presence of halide
      counterions. In the case of biphenol- and BINOL-based phosphoramidites, however,
      a strong memory effect is observed when 1-phenyl-2-propenyl acetate is employed
      as the substrate. In this case, nucleophilic attack competes effectively with the
      isomerisation of the transient cinnamylpalladium complexes. The asymmetric
      allylic alkylation of 1,3-diphenyl-2-propenyl acetate afforded the chiral product
      in up to 93 % ee. Substrates with smaller substituents gave lower
      enantioselectivities. The observed stereoselectivity is explained in terms of a
      preferential rotation mechanism, in which the product is formed by attack on one
      of the isomers of the intermediate [Pd[1,3-(C6H5)2C3H3](L)(OAc)] complex.

PMID- 15515070
TI  - Synthesis and characterization of nanocast silica NCS-1 with CMK-3 as a template.
AB  - Nanocast silica (NCS-1) was synthesized by a casting process by employing the
      mesoporous carbon CMK-3 (the replica of SBA-15) as a template, tetraethoxysilane
      (TEOS) as the silica source, and hydrochloric acid (HCl) as the catalyst. The
      ordered carbon template was removed by employing different methods, such as
      calcination, thermal treatment followed by calcination, and controlled
      combustion. According to XRD and TEM characterization, NCS-1 exhibits an ordered
      structure with hexagonal symmetry and retains the morphology of the original SBA
      15 used for the synthesis of CMK-3 over two replication steps on the nanometer
      scale. This demonstrates the well-connected porosity in CMK-3 type carbon, which
      can be used as a mold to synthesize mesostructured materials. The nitrogen
      adsorption isotherms generally show type IV shape, indicating mesoporous
      characteristics. The structure of NCS-1 is strongly influenced by variables of
      the nanocasting process, such as the loading amount of silica, hydrolysis
      temperature, and carbon removal methods. The surface area, pore size, and pore
      volume of NCS-1 can be tuned to a certain range by varying these parameters.

PMID- 15515071
TI  - cis/trans photoisomerization of secondary thiopeptide bonds.
AB  - The reversible cis/trans photoisomerization of secondary thiopeptide bonds has
      been systematically studied with UV-visible absorption, capillary
      electrophoresis, 1H NMR spectroscopy, and circular dichroism methods. It was
      found that the concentration of the cis conformers could be increased from less
      than 1 % in the thermal equilibrated solution to up to 20 % in the
      photostationary state. The rotational barriers of the thiopeptide bond and the pH
      dependence of the isomerization rates were also studied. The quantum yields of
      the trans-->cis and the cis-->trans processes were determined from photokinetic
      analysis.

PMID- 15515072
TI  - Microwave-assisted synthesis of metallic nanostructures in solution.
AB  - Microwave (MW) rapid heating has received considerable attention as a new
      promising method for the one-pot synthesis of metallic nanostructures in
      solutions. In this concept, advantageous application of this method has been
      demonstrated by using some typical examples for the preparation of Ag, Au, Pt,
      and AuPd nanostructures. Not only spherical nanoparticles, but also single
      crystalline polygonal plates, sheets, rods, wires, tubes, and dendrites were
      prepared within a few minutes under MW heating. Morphologies and sizes of
      nanostructures could be controlled by changing various experimental parameters,
      such as the concentration of metallic salt and surfactant polymer, the chain
      length of the surfactant polymer, the solvent, and the reaction temperature. In
      general, nanostructures with smaller sizes, narrower size distributions, and a
      higher degree of crystallization were obtained under MW heating than those in
      conventional oil-bath heating. The origin of these characteristic features under
      MW irradiation is discussed in terms of thermal and non-thermal effects under MW
      irradiation.

PMID- 15515073
TI  - Mass spectrometric investigation of noncovalent complexation between a
      tetratosylated resorcarene and alkyl ammonium ions.
AB  - Noncovalent complexation between tetratosylated tetraethyl resorcarene (1) and
      primary, secondary, and tertiary alkyl ammonium ions (mMe, dMe, tMe, mEt, dEt,
      tEt, dBu, and dHex) was studied by electrospray ionization Fourier transform ion
      cyclotron resonance (ESI-FTICR) mass spectrometry. Interactions of the
      noncovalent complexes were investigated by means of competition experiments,
      collision-induced dissociation (CID) experiments, ion-molecule reactions with
      tripropylamine and gas phase H/D-exchange reactions with deuteroammonia. Gas
      phase ion-molecule reactions gave especially valuable information about the
      structure and properties of the complexes. Resorcarene 1 formed relatively stable
      1:1 complexes with all aliphatic alkyl ammonium ions. Steric properties of the
      alkyl ammonium ions and proton affinities of the conjugate amines noticeably
      affected the complexation properties, indicating the importance of hydrogen
      bonding in these complexes. According to the competition experiments, the
      thermodynamically most stable host-guest complexes were formed with alkyl
      ammonium ions that were most substituted and had the longest alkyl chains. In CID
      experiments, release of an intact free guest ion or dissociation of the host was
      observed to depend on the proton affinity of the amine and the strength of the
      hydrogen bond that was formed. In ion-molecule reactions with tripropylamine, a
      guest exchange reaction occurred with all alkyl ammonium ion complexes with
      reaction rates mostly dependent on the steric properties of the original guest
      ion. In H/D-exchange reactions the N-H hydrogen atoms of the guest ion were
      exchanged with deuterium, whereas the resorcinol hydrogen atoms remained
      unchanged.

PMID- 15515074
TI  - Atmospheric pressure chemical vapor deposition: an alternative route to large
      scale MoS2 and WS2 inorganic fullerene-like nanostructures and nanoflowers.
AB  - Large-scale MoS2 and WS2 inorganic fullerene-like (IF) nanostructures (onionlike
      nanoparticles, nanotubes) and elegant three-dimensional nanoflowers (NF) have
      been selectively prepared through an atmospheric pressure chemical vapor
      deposition (APCVD) process with the reaction of chlorides and sulfur. The
      morphologies were controlled by adjusting the deposition position, the deposition
      temperature, and the flux of the carrier gas. All of the nanostructures have been
      characterized by X-ray powder diffraction (XRD), transmission electron microscopy
      (TEM), and scanning electron microscopy (SEM). A reaction mechanism is proposed
      based on the experimental results. The surface area of MoS2 IF nanoparticles and
      the field-emission effect of as-prepared WS2 nanoflowers is reported.

PMID- 15515075
TI  - Studies on stereoselective [2+2] cycloadditions between N,N-dialkylhydrazones and
      ketenes.
AB  - Staudinger-like cycloadditions between chiral, non-racemic N,N-dialkylhydrazones
      1 and functionalized ketenes constitute an efficient methodology for the
      stereoselective construction of the beta-lactam ring. The potential for fine
      tuning of the dialkylamino auxiliary structure, the availability of a high
      yielding deprotection method for the release of the free azetidinones, and the
      high thermal and chemical stability of hydrazones as N-dialkylamino imines are
      highlighted as the key elements for the success of the strategy. This last aspect
      is of particular importance concerning generality: even hydrazones from easily
      enolizable aldehydes or from formaldehyde reacted to afford the corresponding
      cycloadducts with high chemical and stereochemical yields. The syntheses of the
      beta-amino-alpha-hydroxyacids (2R,3S)-phenylisoserine (42) and (2R,3S)-norstatin
      (45) were accomplished as illustrative examples of the synthetic utility of this
      procedure. A model system for the cycloaddition of g series auxiliaries was
      studied by ab initio computational methods. The collected results support a two
      step mechanism through zwitterionic intermediates, and explain the observed
      absolute and relative stereochemistry in terms of the preferred outward
      cycloaddition to the Re face of the hydrazone.

PMID- 15515076
TI  - A kinetically stabilized ferrocenyl diphosphene: synthesis, structure,
      properties, and redox behavior.
AB  - A new, stable ferrocenyl diphosphene [Tbt-P==P-Fc] (1) (Tbt=2,4,6
      tris[bis(trimethylsilyl)methyl]phenyl, Fc = ferrocenyl) was synthesized by the
      dehydrochlorination reaction of the corresponding diphosphane, [Tbt-P(H)-P(Cl)
      Fc] (8), with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in good yield. Diphosphene
      1 is very stable in the solid state and also in solution. In the 31P NMR spectrum
      (C6D6), diphosphene 1 showed a low-fielded AB quartet at delta 501.7 and 479.5
      ppm with the coupling constant 1J(PP)=546 Hz, which is characteristic of an
      unsymmetrically substituted trans-diphosphene. The molecular structure of 1 was
      established by X-ray crystallographic analysis, which showed a trans-diphosphene
      with a C-P-P-C torsion angle of 177.86(17) degrees . The phosphorus-phosphorus
      bond length of 1 [2.0285(15) A] which is considerably shorter than the typical P
      P single-bond lengths (ca. 2.22-2.24 A) and within the range of reported P=P
      double-bond lengths (1.985-2.051 A) for diaryl diphosphenes, evidenced the P=P
      double-bond character of 1 in the solid state. In addition, the cyclic
      voltammograms of 1 showed reversible reduction and oxidation couples at -1.95 and
      +0.34 V versus SCE, respectively. The electrochemical results for 1 were
      reasonably supported by the DFT calculations, which suggested that the LUMO and
      HOMO orbitals should be mainly pi* orbital of the diphosphene moiety and d
      orbitals of the iron(II) atom, respectively.

PMID- 15515078
TI  - Recognition of remote mismatches by DNA polymerases.

PMID- 15515077
TI  - Oxidosqualene cyclase second-sphere residues profoundly influence the product
      profile.

PMID- 15515079
TI  - Structural modifications enable conserved peptides to fit into MHC molecules thus
      inducing protection against malaria.

PMID- 15515080
TI  - Site-specific multivalent carbohydrate labeling of quantum dots and magnetic
      beads.

PMID- 15515081
TI  - Common inhibition of both beta-glucosidases and beta-mannosidases by isofagomine
      lactam reflects different conformational itineraries for pyranoside hydrolysis.

PMID- 15515082
TI  - Chemistry meets biology: chemical approaches to the study of biology.

PMID- 15515084
TI  - Peroxidase activity of cationic metalloporphyrin-antibody complexes.
AB  - Peroxidase activity of a complex of water-soluble cationic metalloporphyrin with
      anti-cationic porphyrin antibody is reported. Antibody 12E11G, which was prepared
      by immunization with a conjugate of 5-(4-carboxyphenyl)-10,15,20-tris(4
      methylpyridyl)porphine iodide (3MPy1C), bound to tetramethylpyridylporphyrin iron
      complex (FeIII-TMPyP) with the dissociation constant of 2.6 x 10(-7) M. The
      complex of antibody 12E11G with FeIII-TMPyP catalyzed oxidation of pyrogallol,
      catechol, and guaiacol. A Lineweaver-Burk plot for the oxidation of pyrogallol
      catalyzed by the FeIII-TMPyP-antibody complex showed Km=8.6 mM and kcat=680 min(
      1). Under the same conditions, Km and kcat for horseradish peroxidase (HRP) were
      0.8 mM and 1750 min(-1), respectively. Although the binding interaction of the
      antibody to the substrates was one order lower than that of native HRP, the
      peroxidase activity of this system was in the same order of magnitude as that of
      HRP.

PMID- 15515085
TI  - Gaseous supramolecules of imidazolium ionic liquids: "magic" numbers and
      intrinsic strengths of hydrogen bonds.
AB  - Electrospray ionization mass spectrometry (ESI-MS) is found to gently and
      efficiently transfer small to large as well as singly to multiply charged [X+]n[A
      ]m supramolecules of imidazolium ion (X+) ionic liquids to the gas phase, and to
      reveal "magic numbers" for their most favored assemblies. Tandem mass
      spectrometric experiments (ESI-MS/MS) were then used to dissociate, via low
      energy collision activation, mixed and loosely bonded [A- - - -X- - - -A']- and
      [X- - - -A- - - -X']+ gaseous supramolecules, as well as their higher homologues,
      and to estimate and order via Cooks' kinetic method (CKM) and B3LYP/6-311G(d,p)
      calculations the intrinsic solvent-free magnitude of hydrogen bonds. For the five
      anions studied, the relative order of intrinsic hydrogen-bond strengths to the 1
      n-butyl-3-methylimidazolium ion [X1]+ is: CF3CO2- (zero) > BF4- (-3.1) > PF6- (
      10.0) > InCl4- (-16.4) and BPh4- (-17.6 kcal mol(-1)). The relative hydrogen-bond
      strength for InCl4- was measured via CKM whereas those for the other anions were
      calculated and used as CKM references. A good correlation coefficient (R=0.998)
      between fragment ion ratios and calculated hydrogen-bond strengths and an
      effective temperature (Teff) of 430 K demonstrate the CKM reliability for
      measuring hydrogen-bond strengths in gaseous ionic liquid supramolecules. Using
      CKM and Teff of 430 K, the intrinsic hydrogen-bond strengths of BF4- for the
      three cations investigated is: 1-n-butyl-3-methyl-imidazolium ion (0) > 1,3-di
      [(R)-3-methyl-2-butyl]-imidazolium ion (-2.4) > 1,3-di-[(R)-alpha-methylbenzyl]
      imidazolium ion (-3.0 kcal mol(-1)). As evidenced by "magic" numbers, greater
      stabilities are found for the [(X1)2(BF4)3]- and [(X1)5A4]+ supramolecules (A not
      equal InCl4-).

PMID- 15515087
TI  - Integrating input from multiple signals: the VirA/VirG two-component system of
      Agrobacterium tumefaciens.
AB  - Bacteria, fungi, and plants exploit histidine sensor kinase/response regulators
      to mobilize complex responses to inputs as diverse as environmental stimuli and
      hormonal regulation. More than 50 such two-component systems are found in many
      organisms, yet the mechanisms of signal perception, phosphotransfer regulation,
      and even the nature of the activating signals remain poorly defined. Here we
      resolve each phosphate transfer event in vivo for the Agrobacterium tumefaciens
      virulence two-component system VirA/VirG. The input signals for this system are
      known, and the complex autocatalytic regulation of the signaling components has
      been removed. Two separate and independent phosphotransfer events are resolved,
      an initial ATP-->sensorHis approximately PO(4)-->receiver approximately PO(4),
      that may be activated by xenognostic sugar/low pH, and a subsequent ATP-->His
      approximately PO(4)-->VirG approximately PO(4) that requires xenognostic phenol
      activation. The identification of these separate pathways places biochemical
      limits on the regulated steps in this two-component signal transduction module
      and further extends the model of how a single sensor is able to integrate
      multiple input stimuli.

PMID- 15515086
TI  - Cofactor-apoprotein hydrogen bonding in oxidized and fully reduced flavodoxin
      monitored by trans-hydrogen-bond scalar couplings.
AB  - Hydrogen bonding plays a key role in the tight binding of the FMN cofactor and
      the regulation of its redox properties in flavodoxins. Hydrogen bonding
      interactions can be directly observed in solution by multidimensional
      heteronuclear NMR spectroscopy through the scalar couplings between donor and
      acceptor nuclei. Here we report on the detection of intermolecular trans-hydrogen
      bond couplings ((h)J) between the flavin ring system and the backbone of
      Desulfovibrio vulgaris flavodoxin in the oxidized and the two-electron reduced
      states. For this purpose, experiments are adapted from pulse sequences previously
      applied to determining (h)J coupling constants in nucleic acid-base pairs and
      proteins. The resulting (h2)J(N,N), (h4)J(N,N), (h3)J(C,N), and (h1)J(H,N)
      couplings involve the (15)N(1), (13)C(2), and (15)N(3) nuclei of the pyrimidine
      moiety of FMN, whereas no such interactions are detectable for (13)C(4) and
      (15)N(5). Several long-range (15)N-(15)N, (13)C-(15)N, and (1)H-(15)N J-coupling
      constants within the flavin are obtained as "by-products". The magnitudes of both
      (h)J and regular J couplings are found to be dependent on the redox state. In
      general, good correlations between (h)J coupling constants and donor-group (1)H
      chemical shifts and also crystallographic donor-acceptor distances are observed.

PMID- 15515088
TI  - Analysis of platinum adducts with DNA nucleotides and nucleosides by capillary
      electrophoresis coupled to ESI-MS: indications of guanosine 5'-monophosphate O6
      N7 chelation.
AB  - DNA is the ultimate target of platinum-based anticancer therapy. Since the N7 of
      guanine is known to be the major binding site of cisplatin and its analogues,
      adduct formation with model nucleotides, especially 2'-deoxyguanosine 5'
      monophosphate (dGMP), has been studied in detail. During the last few years a
      coupled capillary eletrophoresis/electrospray-ionization mass spectrometry
      (CE/ESI-MS) method has been advantageously used in order to separate and identify
      platinum adducts with nucleotides in submillimolar concentrations in aqueous
      solutions. Beside the bisadduct, [Pt(NH(3))(2)(dNMP)(2)](2-) (NMP=2'
      deoxynucleoside 5'-monophosphate), and the well-known monochloro and monohydroxo
      adducts, [Pt(NH(3))(2)Cl(dNMP)](-) and [Pt(NH(3))(2)(dNMP)OH](-), respectively, a
      third kind of monoadduct species with a composition of [Pt(NH(3))(2)(dNMP)](-)
      can be separated by CE and detected through the m/z values measured with ESI-MS.
      Different experimental setups indicate the existence of an O(6)-N7 chelate,
      whereas the formation of N7-alphaPO(4) macrochelates or dinuclear species is
      unlikely. Additionally, offline MS experiments with 2'-deoxyguanosine (dG) and
      stabilization of the controversially discussed O(6)-N7 chelate by oxidation with
      hydrogen peroxide support the assumption of the existence of O(6)-N7 chelation.

PMID- 15515089
TI  - Triple-helix directed cleavage of double-stranded DNA by benzoquinoquinoxaline
      1,10-phenanthroline conjugates.
AB  - Oligonucleotide-directed triple-helix formation provides a rational means to
      interfere with genomic DNA targets and to direct modifications at specific sites.
      We have developed a new class of compounds that, at low concentrations,
      efficiently targets and damages double-stranded DNA specifically at the site
      where a triple-helical structure is formed. In these new compounds, a triple
      helix-specific intercalator-benzoquinoquinoxaline (BQQ)-was coupled to one of two
      isomeric 1,10-phenanthrolinecarboxaldehyde derivatives. 1,10-Phenanthroline
      derivatives are known to cleave DNA in the presence of copper ions. The obtained
      BQQ-1,10-phenanthroline (BQQ-OP) conjugates were compared with regard to their
      ability to cleave triple-helix DNA. Both conjugates displayed a sequence
      preference inside the triple-helical site, as judged from the more pronounced
      cleavage obtained at stretches of TAxT base triplets.

PMID- 15515090
TI  - Function of lanGT3, a glycosyltransferase gene involved in landomycin A
      biosynthesis.
AB  - The glycosyltransferase gene lanGT3, involved in the biosynthesis of the
      angucyclic antibiotic landomycin A, has been characterised by targeted gene
      deletion. A lanGT3 mutant was shown to produce landomycin E, which consists of a
      trisaccharide side chain attached to the polyketide moiety. Expression of lanGT3
      in the mutant restored landomycin A production. Our results indicate that LanGT3
      is responsible for the transfer of the fourth sugar during landomycin A
      biosynthesis.

PMID- 15515091
TI  - Entropically assisted carbohydrate recognition by a natural killer cell-surface
      receptor.

PMID- 15515092
TI  - The core structures of roseophilin and the prodigiosin alkaloids define a new
      class of protein tyrosine phosphatase inhibitors.

PMID- 15515093
TI  - An axial met ligand at a type 1 copper site is preferable for fast electron
      transfer.

PMID- 15515094
TI  - Palladium-catalyzed asymmetric allylic alkylation of ketone enolates.
AB  - Palladium-catalyzed asymmetric allylic alkylation of nonstabilized ketone
      enolates to generate quaternary centers has been achieved in excellent yield and
      enantioselectivity. Optimized conditions consist of performing the reaction in
      the presence of two equivalents of LDA as base, one equivalent of trimethytin
      chloride as a Lewis acid, 1,2-dimethoxyethane as the solvent, and a catalytic
      amount of a chiral palladium complex formed from pi-allyl palladium chloride
      dimer 3 and cyclohexyldiamine derived chiral ligand 4. Linearly substituted,
      acyclic 1,3-dialkyl substituted, and unsubstituted allylic carbonates function
      well as electrophiles. A variety of alpha-tetralones, cyclohexanones, and
      cyclopentanones can be employed as nucleophiles. The absolute configuration
      generated is consistent with the current model in which steric factors control
      stereofacial differentiation. The quaternary substituted products available by
      this method are versatile substrates for further elaboration.

PMID- 15515095
TI  - Systematic survey on the prevalence of genes coding for staphylococcal
      enterotoxins SElM, SElO, and SElN.
AB  - Staphylococcus aureus remains a leading cause of food-poisoning with substantial
      impact on public health. Using a multiplex polymerase chain reaction-DNA enzyme
      immunoassay (PCR-DEIA), we studied the presence of genes encoding staphylococcal
      enterotoxin-like (SEl) superantigens sem, sen, and seo, associated with the
      enterotoxin gene cluster (egc), in 429 clinical Staphylococcus aureus isolates.
      294 (68.5%) isolates tested positive for at least one of the three SEl genes. In
      contrast to the fixed gene combination seg/sei also located on egc, a substantial
      number of isolates (n = 108) were found to bear only one or two of the genes
      encoding SElM, SElN, and SElO. Regarding the origin of the S. aureus isolates, a
      significant difference (P = 0.022) was found for the possession of seo (61.2% of
      blood isolates versus 42.9% of nasal strains). Also sem (not significantly) was
      found more common in blood isolates (52.1% versus 40.5%). The survey of the newly
      described SEl genes sem-seo supports the concept that most clinical S. aureus
      isolates harbor subsets of pyrogenic toxin superantigens. The potential
      contribution of seo and sem to the pathogenic potential of S. aureus has to be
      further evaluated.

PMID- 15515098
TI  - Key players involved in bacterial disulfide-bond formation.

PMID- 15515099
TI  - Identification of the luciferin-luciferase system and quantification of
      coelenterazine by mass spectrometry in the deep-sea luminous ostracod Conchoecia
      pseudodiscophora.
AB  - The bioluminescence system of the ostracod Conchoecia pseudodiscophora, which is
      abundant in the Sea of Japan, has been characterized. The luminescence
      (lambda(max)=463 nm) is produced by a luciferin-luciferase reaction, and the
      luciferin has been identified as coelenterazine. Coelenterazine, coelenteramide,
      and coelenteramine from C. pseudodiscophora were quantified by LC-ESI-MS/MS
      analysis. The coelenterazine content was estimated to be approximately 230 pg per
      animal by using a calibration curve of synthetic coelenterazine. The reaction
      between homogenates of C. pseudodiscophora and synthetic coelenterazine showed
      luminescence activity; this suggests that a coelenterazine-type luciferase is
      present.

PMID- 15515100
TI  - Modified oligonucleotides containing lithocholic acid in their backbones: their
      enhanced cellular uptake and their mimicking of hairpin structures.
AB  - Their enhanced cell permeability and their ability to mimic DNA structures make
      modified oligodeoxyribonucleotides (ODNs) very important substances for
      increasing our understanding of cell biology and for therapeutic applications.
      Lithocholic acid is a hydrophobic secondary bile acid that is a substrate of
      nuclear Pregnane X receptor (PXR). We designed and synthesized novel lithocholic
      acid-based ODNs (L-ODNs) by using a new phosphoramidite derived from lithocholic
      acid. By comparing data obtained from circular-dichroism, melting-point, and
      theoretical studies, we believe that these L-ODNs adopt DNA hairpin structures.
      Furthermore, L-ODNs have enhanced cellular uptake properties with respect to
      regular ODNs. To demonstrate their enhanced cell permeabilities, we carried out
      cellular uptake experiments of L-ODNs in HeLa cells. By attaching fluorescein as
      a fluorescence label and using confocal microscopy, we observed that the
      permeability of L-ODNs is much higher than that of natural ODNs.

PMID- 15515101
TI  - Novel rhodium-catalyzed reaction of thiazolidine derivatives with carbodiimides.
AB  - A new, simple, and regioselective synthesis of thiazolidinimine derivatives based
      on the rhodium-catalyzed reaction of readily available thiazolidines with
      carbodiimides is described. This methodology provides direct access to a large
      variety of thiazolidinimine derivatives, possibly via a novel regiospecific
      insertion of carbodiimides into one of two ring carbon-nitrogen bonds, as well as
      a metal-catalyzed imine elimination process.

PMID- 15515102
TI  - On the role of PIII ligands in the conjugate addition of diorganozinc derivatives
      to enones.
AB  - A mechanistic study on the conjugate addition of diethylzinc to cyclohexenone
      catalyzed by various chiral PIII ligands, provides new insights into its
      mechanism. Complete in situ conversion of the catalytic amount of Cu(OTf)2 into
      CuI species by excess ZnEt2 is demonstrated by EPR spectroscopy. Experimental
      evidence is presented in favor of a critical ternary 1:1:1 complex between enone,
      Et2Zn and catalyst, supporting a rate-limiting reductive elimination or
      carbocupration from a preformed mixed Cu/Zn cluster carrying one- or two-ligand
      molecules. A crystal structure has been obtained for a CuIL2 complex, which shows
      catalytic turnover on addition of reagent and substrate. NMR spectroscopic
      analyses and VT experiments reveal that steric hindrance may prevent complexation
      of a second ligand molecule on the CuI cation, leading to extremely fast
      precatalysts based on CuX.L species.

PMID- 15515103
TI  - Selection of a pentameric host in the host-guest complexes [[[[P(mu-NtBu)]2(mu
      NH)]5].I]-[Li(thf)4]+ and [[[P(mu-NtBu)]2(mu-NH)]5].HBr.THF.
AB  - The structures of the host-guest complexes [[[[P(mu-NtBu)]2(mu-NH)]5]I]
      .[Li(thf)4]+ [2.I[Li(thf)4]] and [[[P(mu-NtBu)]2(mu-NH)]5].HBr.THF (2.HBr.THF)
      show that increased distortion of the framework of the pentameric macrocycle
      [[[P(mu-NtBu)]2(mu-NH)]5] (2) occurs with the larger halide ions. Theoretical
      studies show that the thermodynamic stabilities of the model host-guest anions
      [2.X]- (X=Cl, Br, I) are in the order Cl- approximately Br->I-, that is, the
      reverse of the templating trend observed experimentally. These studies support
      the view that the selection of the pentamer 2 over the tetramer [[[P(mu
      NtBu)]2(mu-NH)]4] (1) is kinetically controlled, a conclusion which is also
      consistent with the previous observation that the frameworks of 1 and 2 are not
      in dynamic equilibrium with each other.

PMID- 15515104
TI  - Theoretical study on the reactivities of stannylene and plumbylene and the origin
      of their activation barriers.
AB  - The potential energy surfaces corresponding to the reactions of heavy carbenes
      with various molecules were investigated by employing computations at the B3LYP
      and CCSD(T) levels of theory. To understand the origin of barrier heights and
      reactivities, the model system (CH3)2X+Y (X=C, Si, Ge, Sn, and Pb; Y=CH4, SiH4,
      GeH4, CH3OH, C2H6, C2H4, and C2H2) was chosen for the present study. All
      reactions involve initial formation of a precursor complex, followed by a high
      energy transition state, and then a final product. My theoretical investigations
      suggest that the heavier the X center, the larger the activation barrier, and the
      less exothermic (or the more endothermic) the chemical reaction. In particular,
      the computational results show that (CH3)2Sn does not insert readily into C-H, Si
      H, C-H, Ge-H, or C-C bonds. It is also unreactive towards C=C bonds, but is
      reactive towards C identical with C and O-H bonds. My theoretical findings are in
      good agreement with experimental observations. Furthermore, a configuration
      mixing model based on the work of Pross and Shaik is used to rationalize the
      computational results. It is demonstrated that the singlet-triplet splitting of a
      heavy carbene (CH3)2X plays a decisive role in determining its chemical
      reactivity. The results obtained allow a number of predictions to be made.

PMID- 15515105
TI  - Early impact of centralization of oesophageal cancer surgery services.
AB  - BACKGROUND: In response to national guidance, oesophageal surgery from four
      hospitals within Wessex was centralized to a single site, with a provision for
      surgeons to travel to the centre to operate if they wished. This study assessed
      the clinical impact of this change. METHODS: Data for patients who had
      oesophageal cancer surgery at the single site were collected prospectively for 1
      year from May 2002 and compared with the Wessex Oesophageal Cancer Audit (WOCA)
      data for the four hospitals from 1999 to 2000. RESULTS: Thirty-three patients
      underwent surgery on the single site compared with 40 patients from the four
      hospitals during the WOCA. Age, sex, co-morbidity, tumour site, and preoperative
      tumour and node stage were similar in the two groups. Six patients from the WOCA
      underwent 'open and close' laparotomy compared with none in the single-site group
      (P = 0.020). There were four anastomotic leaks in the WOCA group and two in the
      single-site group. Overall complication rates in those undergoing resection were
      similar in the two groups, but the in-hospital mortality rate was significantly
      higher in the WOCA group (five versus no patients; P = 0.022). Pathology
      reporting was incomplete in significantly more patients in the WOCA group (15
      versus three; P = 0.001). The mean node harvest was greater in the single-site
      group (30.5 versus 19). CONCLUSION: Centralization of oesophageal surgery
      resulted in better preoperative staging, a lower 30-day mortality rate and more
      complete pathological reporting.

PMID- 15515106
TI  - Presentation, treatment and outcome in patients with ampullary tumours.
AB  - BACKGROUND: Ampullary tumours are relatively rare, and few large single-centre
      reports provide information on their treatment and outcome. The aim of this study
      was to analyse outcome and determine predictors of survival for patients with
      ampullary tumours treated in a specialist centre. METHODS: Over an 11-year
      period, 561 patients were treated for periampullary tumours, 88 of whom had a
      histologically proven ampullary neoplasm. Prospectively gathered data were
      analysed to assess predictors of survival. RESULTS: The overall resection rate
      was 92 per cent; there were no postoperative deaths. Median survival was 45.8
      months for patients with resectable tumours and 8.0 months for those with
      irresectable disease (P < 0.001). On univariate analysis, age less than 70 years
      (P = 0.015) and a bilirubin level of 75 micromol/l or less (P = 0.012) favoured
      long-term survival. Among 70 patients who underwent cancer resection, factors
      associated with significantly worse long-term survival on univariate analysis
      included poorly differentiated tumour (P < 0.001), positive nodes (P < 0.001),
      perineural invasion (P = 0.001) and invasion of the pancreas (P = 0.018).
      Multivariate analysis identified positive nodes and bilirubin concentration as
      independent predictors of survival. CONCLUSION: An aggressive surgical approach
      to ampullary tumours is justified by the low proportion of benign lesions, the
      absence of postoperative mortality and improved long-term survival.

PMID- 15515108
TI  - Analysis of antioxidant compounds in sweet orange peel by HPLC-diode array
      detection-electrospray ionization mass spectrometry.
AB  - HPLC-diode array detection-electrospray ionization mass spectrometry was used to
      determine qualitatively and quantitatively the flavonoid content of several
      fractions and residues of extracts of Greek navel sweet orange peel (Citrus
      sinensis) from the region of southern Greece (Leonidi-Tripoli). The main groups
      of flavonoids found according to HPLC retention times, spectral data and
      literature references were polymethoxylated flavones, C-glycosylated flavones, O
      glycosylated flavones, O-glycosylated flavanones, flavonols and phenolic acids
      and their derivatives. The ethyl acetate fraction which has been shown in
      previous work to possess the best radical scavenging activity among the others
      was found to contain C-glycosylated flavones, polymethoxylated flavones, O
      glycosylated flavones, O-glycosylated flavanones, two phenolic acid derivatives
      and two unknown compounds, all in low concentrations. The group of C-glycosylated
      flavones was reported for the first time in the peel of Navel sweet orange. The C
      glycosylated flavones found according to their spectral characteristics and
      literature were 6-C-beta-glucosyldiosmin, 6,8-di-C-glucopyranosylapigenin, 6,8-di
      C-beta-glucosyldiosmin and two unknown. The results suggest that the ethyl
      acetate fraction of navel Citrus sinensis peel consists of significant
      antioxidant compounds and can be used as a food additive of natural origin or a
      pharmaceutical supplement using as a source of peel the byproducts of the orange
      juice industry.

PMID- 15515109
TI  - Quantitative structure-retention relationships for ionic and non-ionic compounds
      in biopartitioning micellar chromatography.
AB  - Quantitative structure-retention relationships, QSRRs, represent a powerful tool
      in chromatography. The objectives of QSRR studies are to predict the
      chromatographic retention behaviour of solutes based on their structural
      properties, to elucidate retention mechanisms, to optimize the separation of
      complex mixtures or to prepare experimental designs. In this paper, using the
      retention factors of 151 structurally unrelated solutes that cover a wide range
      of hydrophobicity, molecular size, hydrogen bonding properties and ionization
      degrees obtained in biopartitioning micellar chromatography (BMC) at different
      Brij35 micellar concentrations, several multivariate QSRR models are tested. It
      is demonstrated that the chromatographic retention of any molecule in BMC,
      independently of its family, can be adequately described by its hydrophobicity
      (expressed as log P) and its anionic and cationic total molar charge (expressed
      as alpha(A) and alpha(B)).

PMID- 15515110
TI  - Liquid chromatographic enantioseparation of aryl alpha-amino ketones on a crown
      ether-based chiral stationary phase.
AB  - A liquid chromatographic chiral stationary phase based on (3,3'-diphenyl-1,1'
      binaphthyl)-20-crown-6 covalently bonded to silica gel was applied in the
      resolution of aryl alpha-amino ketones including cathinone, the main psychoactive
      alkaloid found in the leaves of the khat plant. The resolution was excellent, the
      separation factors ranging between 1.72 and 8.58 and the resolution factors
      (R(S)) ranging between 2.60 and 11.10. The chromatographic resolution behaviour
      was dependent on the type and the content of organic and acidic modifiers and the
      ammonium acetate concentration in aqueous mobile phase and the column
      temperature.

PMID- 15515111
TI  - Survival of patients with periampullary carcinoma is predicted by lymph node 8a
      but not by lymph node 16b1 status.
AB  - BACKGROUND: The aim of this study was to assess the impact of metastatic disease
      in lymph nodes 8a and 16b1 (as defined by the Japanese Pancreas Society) on
      survival in patients with periampullary malignancy. METHODS: Patients undergoing
      resection for primary pancreatic ductal adenocarcinoma or intrapancreatic bile
      duct adenocarcinoma were identified from a prospective database (September 1997
      May 2003). RESULTS: Thirteen of 54 and ten of 44 evaluable patients had
      metastatic involvement of lymph nodes 8a and 16b1 respectively. Metastatic
      involvement of lymph node 8a was associated with a significantly shorter median
      survival (197 versus 470 days; P = 0.003) but metastatic involvement of lymph
      node 16b1 did not affect survival (457 versus 503 days; P = 0.185). Multivariate
      analysis showed lymph node 8a status to be the strongest predictor of outcome (P
      = 0.006). Median survival of those with metastatic lymph node 8a was not
      significantly different from that of 81 patients with overt metastatic
      periampullary cancer at the time of diagnosis (98 days; P = 0.072) CONCLUSION:
      Lymph node 8a was an independent prognostic factor in patients with periampullary
      malignancy, but lymph node 16b1 was not. Survival in those with metastatic lymph
      node 8a was not significantly different from that in patients with metastatic
      disease at presentation. Preoperative determination of lymph node 8a status may
      have important implications in selecting patients for treatment.

PMID- 15515112
TI  - Five-year follow-up of a randomized trial to assess pain and numbness after
      laparoscopic or open repair of groin hernia.
AB  - BACKGROUND: Claims that laparoscopic groin hernia repair is followed by less
      persisting pain and numbness than open mesh repair were tested by follow-up
      within a multicentre randomized clinical trial. METHODS: Participants in the UK
      Medical Research Council Laparoscopic Groin Hernia Trial were followed up by
      means of self-completed postal questionnaires from 2 to 5 years after trial
      entry. The principal measures were pain (groin and testicular) and numbness
      (groin and thigh). RESULTS: Seven hundred and fifty (80.8 per cent) of the
      original 928 participants returned at least one questionnaire between 2 and 5
      years; respondents were similar to the baseline randomized groups. Fewer
      respondents in the laparoscopic group had groin pain (absolute differences varied
      between 7.9 and 2.0 per cent, but were of marginal statistical significance);
      rates of testicular pain were similar in the two groups. Groin numbness was
      reported about half as commonly at all time points in the laparoscopic group (P <
      0.001); there were no significant differences in thigh numbness. CONCLUSION:
      Laparoscopic surgery was associated with less long-term numbness and probably
      less pain in the groin.

PMID- 15515113
TI  - Protective effects of melatonin against carbon tetrachloride hepatotoxicity in
      rats.
AB  - Melatonin is an indolamine, mainly secreted by the pineal gland into the blood of
      mammalian species. The potential for protective effects of melatonin on carbon
      tetrachloride (CCl(4))-induced acute liver injury in rats was investigated in
      this work. CCl(4) exerts its toxic effects by generation of free radicals; it was
      intragastrically administered to male Wistar rats (4 g kg(-1) body weight) at 20
      h before the animals were decapitated. Melatonin (15 mg kg(-1) body weight) was
      administered intraperitoneally three times: 30 min before and at 2 and 4 h after
      CCl(4) injection. Rats injected with CCl(4) alone showed significant lipid and
      hydropic dystrophy of the liver, massive necrosis of hepatocytes, marked
      increases in free and conjugated bilirubin levels, elevation of hepatic enzymes
      (alanine aminotransferase and aspartate aminotransferase) in plasma, as well as
      NO accumulation in liver and in blood. Melatonin administered at a
      pharmacological dose diminished the toxic effects of CCl(4). Thus it decreased
      both the structural and functional injury of hepatocytes and clearly exerted
      hepatoprotective effects. Melatonin administration also reduced CCl(4)-induced NO
      generation. These findings suggest that the effect of melatonin on CCl(4)-induced
      acute liver injury depends on the antioxidant action of melatonin.

PMID- 15515114
TI  - Characterization of the ultrastructure of gingival mast cells in alloxan-induced
      diabetic rats.
AB  - The morphological changes of gingival mast cells of alloxan-induced diabetic rats
      were studied by electron microscopy. The following observations were made. The
      cell nucleus and cytoplasm degenerated. The electron density of the granules in
      the cell cytoplasm clearly decreased. Some granules had dense irregular threads
      and the granules were surrounded by a thin vacuole. A ghost vacuole formed in
      some mast cells and disorganized materials accumulated in the cytoplasm. The mast
      cell nuclei were generally irregular and degenerating mast cells had pyknotic
      nuclei. General destruction of the cell membrane and granule shedding in some
      samples was noted and mitochondria with atypical cristae in the cytoplasm of the
      mast cells were seen. We conclude that the characteristics of the ultrastructure
      of gingival mast cells in diabetics are distinctive and should be used as
      criteria for pathogenesis of gingival inflammation.

PMID- 15515115
TI  - Myocardial gene transfer and long-term expression following intracoronary
      delivery of adeno-associated virus.
AB  - Adeno-associated viral vectors (AAV) can direct long-term gene expression in post
      mitotic cells. Previous studies have established that long-term cardiac gene
      transfer results from intramuscular injection into the heart. Cardiac gene
      transfer after direct intracoronary delivery of AAV in vivo, however, has been
      minimal in degree, and indirect intracoronary delivery, an approach used in an
      increasing number of studies, appears to be receiving more attention. To
      determine the utility of indirect intracoronary gene transfer of AAV, we used
      aortic and pulmonary artery cross clamping followed by proximal aortic injection
      of AAV encoding enhanced green fluorescent protein (AAV.EGFP) at 10(11) DNase
      resistant particles (drp; high-performance liquid chromatography (HPLC)-purified)
      per rat. Gene expression was quantified by fluorescent microscopy at four time
      points up to 1 year after vector delivery, revealing 20-32% transmural gene
      expression in the left ventricle at each time point. Histological analysis
      revealed little or no inflammatory response and levels of transgene expression
      were low in liver and undetectable in lung. In subsequent studies in pigs, direct
      intracoronary delivery into the left circumflex coronary artery of AAV.EGFP (2.64
      5.28 x 10(13) drp; HPLC-purified) resulted in gene expression in 3 of 4 pigs 8
      weeks following injection with no inflammatory response in the heart. PCR
      analysis confirmed AAV vector presence in the left circumflex perfusion bed.
      These data indicate that intracoronary delivery of AAV vector is associated with
      transgene expression in the heart, providing a means to obtain long-term
      expression of therapeutic genes.

PMID- 15515116
TI  - Uncertainty due to model choice in variant Creutzfeldt-Jakob disease projections.
AB  - For some statistical applications, uncertainty due to unverifiable assumptions
      can be much greater than that arising from the random variability that is
      quantified by conventional confidence intervals. The case of projecting possible
      maximum numbers of eventual deaths due to variant Creutzfeldt-Jakob disease in
      the United Kingdom provides an extreme example of this phenomenon. The need for
      parametric extrapolation of the incubation distribution, along with non
      identifiability of the number of infected persons, makes assumptions very
      influential. Several publications in leading science journals gave upper bounds
      that were 100-fold to 20 000-fold lower than projections from other plausible
      models given here that fit the data about as well. The crucial assumption for
      projections is how the risk of death increases with time since infection, and
      exponential growth is an obvious choice for pessimistic models. Parametric
      extrapolation from the generalized lambda, generalized F, or lognormal
      distributions produced upper bounds much lower than exponential extrapolation
      (i.e. assuming a Gompertz distribution, which fit the data up to early 2002 quite
      well). Had the publications considered such possibilities, they would have
      reached much weaker conclusions and been less suitable for leading general
      science journals. The scientific publication process may have inherent
      disincentives for thorough assessment of uncertainty.

PMID- 15515117
TI  - AdVEGF165 gene transfer increases survival in overdimensioned skin flaps.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is a key regulator of
      angiogenesis. VEGF A also plays an important role in wound healing of the skin by
      promoting angiogenesis and by stimulating blood vessel growth. Therefore we
      tested the hypothesis that flap survival could be increased by the preoperative
      injection of AdVEGF(165). METHODS: We studied the effect of AdVEGF(165) in an
      overdimensioned ischemic random-pattern-flap model in the rat (n = 50) with a
      length-to-width ratio of 4 : 1. VEGF cDNA was administered in two concentrations
      of 5 x 10(8) plaque-forming units (pfU) and 1 x 10(9) pfU using a recombinant
      adenoviral vector. Recombinant virus was injected subdermally 7, 3 or 0 days
      prior to flap harvest for the lower concentration and 7 days prior for the higher
      concentration. Flap survival and necrosis were observed at day 7, the day the
      animals were sacrificed. RESULTS: Adenoviral gene transfer with VEGF(165) 3 and 7
      days before flap harvest showed a significantly increased flap survival of 50%
      together with a significantly reduced necrosis (p < 0.01). Injection using a
      titer of 1 x 10(9) pfU 7 days prior to surgery increased flap survival even more,
      though failing to reach statistical significance compared to the lower
      concentration. VEGF protein concentration in the injected skin was significantly
      higher than in controls (p < 0.01). Flap perfusion was increased as well,
      demonstrated by indocyanine green (ICG) fluoroscopy (p < 0.001). CONCLUSIONS: Our
      results confirm the important role of VEGF(165) on angiogenesis in ischemic
      flaps. Indeed by injecting VEGF(165) at 3 to 7 days preoperatively in a
      concentration of 1 x 10(9) pfU our data show that length-to-width ratio for
      random-pattern-flaps could be increased from 2 : 1 to 3 : 1 and therefore may
      allow a wider range of applications of this simple flap technique.

PMID- 15515118
TI  - Immune responses following salivary gland administration of recombinant adeno
      associated virus serotype 2 vectors.
AB  - BACKGROUND: Gene transfer to salivary glands (SGs) can be accomplished in a
      minimally invasive manner, resulting in stable, long-term secretion of the
      transgene product. Therefore, SGs provide a novel target site for several
      potentially useful clinical gene therapeutics applications. Previous studies have
      indicated that intravenous, intramuscular and intranasal administration of
      recombinant adeno-associated virus serotype 2 (rAAV2) vectors induce host immune
      responses. There are no reported studies on immune responsiveness of rAAV2 vector
      administration to SGs. MATERIAL AND METHODS: Vectors were administered by
      retrograde infusion to the SGs of Balb/c mice in various combinations.
      Thereafter, transgene expression was determined, and evaluations of host innate
      and adaptive immune responsiveness performed over a 56-day period. RESULTS:
      Histological examination of SGs from vector-treated mice showed no significant
      changes in appearance from controls, including the frequency of activated
      macrophage detection. There were also no differences in salivary flow rates among
      experimental groups. In vitro stimulation of splenocytes from mice administered
      rAAV2 showed elevated interferon-gamma levels in culture media. Significant
      titers of neutralizing antibodies to rAAV2 were detected in serum of mice
      following rAAV2 vector administration. While SGs could be transduced with low
      doses of vector it was not possible to repeat the administration and detect
      transduction with the same serotype at low doses. However, repeat administration
      was possible with an alternative serotype (rAAV4). CONCLUSIONS: Following a
      single administration of rAAV2 vectors to SGs there is no significant innate
      immune response. However, rAAV2 vector administration to SGs results in both
      cellular and humoral immune responses. The latter may interfere with the efficacy
      of repeated rAAV2 vector administration.

PMID- 15515119
TI  - A history of research on yeasts 8: taxonomy.

PMID- 15515120
TI  - Double-stranded secondary structures on mRNA induce type I interferon (IFN
      alpha/beta) production and maturation of mRNA-transfected monocyte-derived
      dendritic cells.
AB  - BACKGROUND: The development of dendritic cell (DC)-based vaccines using antigen
      encoding mRNA requires identification of the critical parameters for efficient ex
      vivo loading of DCs. Exogenously delivered mRNA can induce DC activation, but the
      molecular mechanisms involved are unknown. The aim of the present study was to
      identify the means by which mRNA-dependent activation of DCs occurs. METHODS: In
      vitro transcribed mRNA molecules were delivered into porcine monocyte-derived DCs
      (MoDCs) using different non-viral gene transfer procedures. Using the green
      fluorescent protein (GFP) as reporter gene, as well as rhodamine-labeled RNA,
      intracellular delivery and transfection efficiency were assessed by confocal
      microscopy and flow cytometry. DC activation was monitored in terms of MHC class
      II and CD80/86 upregulation, as well as the production of type I interferon (IFN
      alpha/beta). RESULTS: mRNA-lipofected MoDCs produced type I IFN and upregulated
      MHC class II and CD80/86. Computational analysis of the mRNA molecules predicted
      highly ordered secondary structures forming double-stranded RNA (dsRNA). This
      dsRNA was also detectable by immunofluorescence in mRNA-lipofected cells, using
      antibody specific for dsRNA. Digestion of the mRNA prior to lipofection with a
      double-strand-specific RNase, but not a single-strand-specific RNase, abrogated
      DC activation. Impairment of protein kinase R (PKR) with 2-aminopurine also
      interfered with the activation. CONCLUSIONS: Double-stranded secondary structures
      on mRNA delivered by lipofection can activate MoDCs. This could have important
      implications for mRNA-based immunomodulation of DCs, DC-based immunotherapy, and
      formulation of RNA-based vaccines. In addition, this report describes the first
      in vitro steps towards development of a novel large animal model system to
      evaluate DC-based vaccines against infectious diseases.

PMID- 15515121
TI  - Effects of melatonin on 3-nitrotyrosine formation and energy charge ratio in
      guinea pig kidney in LPS-induced stress.
AB  - The aim of this study was to evaluate the effects of Escherichia coli-derived
      lipopolysaccharide on guinea pig kidney by measuring the energy charge ratio and
      3-nitrotyrosine levels. In addition the possible protective role of melatonin
      against lipopolysaccharide-mediated peroxynitrite formation and energy depletion
      of kidney was determined. Guinea pigs were either pretreated with melatonin or
      saline (for the control) followed by intraperitoneal administration of E. coli.
      Six hours after the administration of E. coli, guinea pig kidney ATP, ADP, AMP
      and 3-nitrotyrosine levels were measured by reverse-phase high performance liquid
      chromatography. There was a significant increase in the formation of 3
      nitrotyrosine and decrease in energy charge in the endotoxin-induced group.
      However melatonin administration prevented 3-nitrotyrosine formation while
      failing to prevent or restore changes in the energy charge ratio of the kidney.

PMID- 15515122
TI  - Maternal and fetal plasma adenosine deaminase, xanthine oxidase and
      malondialdehyde levels in pre-eclampsia.
AB  - The aim of this study was to evaluate maternal-fetal plasma adenosine deaminase,
      xanthine oxidase (ADA, XO) activity and malondialdehyde (MDA) levels and the
      relationship between them in pre-eclampsia. Maternal and umbilical cord whole
      blood samples were taken from 29 pre-eclamptic and 33 normal pregnants. The
      plasma ADA, XO activities as well as MDA levels were assayed by
      spectrophotometric methods. MDA levels and ADA, XO activities were found to be
      higher in maternal and fetal plasma in pre-eclamptics than in normal pregnancy.
      The differences were statistically significant between groups (p < 0.05).
      Increased maternal-fetal plasma XO and ADA activities, as a marker of
      immunological disorder, may be related to the pathogenesis of pre-eclampsia. In
      addition, increased MDA levels may be a reflection of increased oxidative stress
      in pre-eclamptics and their fetuses.

PMID- 15515123
TI  - Serum E-selectin and erythrocyte membrane Na+K+ ATPase levels in patients with
      rheumatoid arthritis.
AB  - We conducted this study to assess serum soluble E-selectin (sE-selectin) levels
      and erythrocyte membrane Na(+)K(+) ATPase activity in patients with rheumatoid
      arthritis (RA) and correlate the levels with disease activity. Levels of sE
      selectin were measured in the serum of 20 patients with RA and 20 control
      subjects by an enzyme-linked immunosorbant assay. Na(+)K(+) ATPase activity was
      determined by a colorimetric method in RA patients and healthy controls. There
      were no statistically significant differences between the two groups with respect
      to demographic data such as age and sex (p > 0.05). The serum levels of sE
      selectin, ESR and C-reactive protein (CRP) in RA patients were significantly
      higher than in healthy controls (p < 0.001). Erythrocyte membrane Na(+)K(+)
      ATPase activity was significantly lower in the RA group than in the control group
      (p < 0.001). Correlation analysis revealed significant positive correlations
      between soluble E-selectin and ESR (r = 0.457; p < 0.05) and CRP (r = 0.682; p <
      0.01) levels. There were statistically significant negative correlations between
      erythrocyte membrane Na(+)K(+) ATPase activity and ESR (r = -0.450; p < 0.05) and
      CRP (r = -0.446; p < 0.05) levels. Additionally, a significant negative
      correlations between sE-selectin and Na(+)K(+) ATPase activity was observed (r = 
      0.80; p < 0.001). These results show that decreases in erythrocyte membrane
      Na(+)K(+) ATPase activity and increases in sE-selectin are observed in RA, and
      that increased levels of sE-selectin may also reflect disease status or activity.

PMID- 15515124
TI  - Correlation of gastric mucosal damage with sialic acid profile in rats: effect of
      hydrochloric acid, pepsin and hypertonic saline.
AB  - Sialic acids occupy terminal positions on gastric mucus glycoprotein where they
      contribute to the high viscosity of mucin. Desialylation of mucus may lead to
      degradation of the mucus and eventually to the breakdown of the gastric mucus
      barrier. The effect of a variety of damaging agents (0.1 M HCl, 2 mg ml(-1)
      pepsin and 2 M NaCl) on sialic acid profile was determined in pylorus-ligated
      rats. The relationship between sialic acid, galactose, pyruvate and the extent of
      gastric mucosal damage were studied. Instillation of pepsin significantly
      increased total sialic acid, galactose and macroscopic mucosal lesions in the
      stomach. Instillation of 0.1 M HCl reduced the total sialic acid but this
      decrease was not significant. Acidity led to a significant increase in the amount
      of free sialic acid in the gastric instillates and the macroscopic lesions
      induced by acid was not significantly different from the control animals (0.15 M
      NaCl). 2 M NaCl induced the macroscopic lesions in the stomach and also free
      sialic acid in the instillates. Pepsin potentiates the action of 2 M NaCl. In all
      the agents examined with the exception of acid, it was observed that an increase
      in free sialic acid and galactose was accompanied by gastric mucosal erosion and
      elevation of pyruvate concentration. It is concluded that gastric acidity alone
      is not inherently damaging and that resistance of gastric mucosa to destructive
      agents may be dependent on the integrity of the sialic acids.

PMID- 15515125
TI  - Effect of HCV infection on THP-1 monocytoid cells.
AB  - Hepatitis C virus (HCV) is the main cause of hepatocellular carcinoma in
      industrialized countries. HCV-HIV-1 co-infection occurs frequently among users of
      illicit intravenous drugs, thereby increasing the severity of HIV disease and the
      evolution of chronic active hepatitis towards cirrhosis and hepatocellular
      carcinoma. The present work shows that THP-1 monocytoid cells are susceptible to
      HCV infection, of strain 1b, and that this strain can induce cellular
      modifications in this cell line. Infection of HCV was demonstrated by positivity
      for the E2 antigen within THP-1 cells and by indirect immunofluorescence;
      moreover, HCV-RNA was detected in supernatants of THP-1 cells from day 7 post
      inoculation. Cell shape and membrane surface antigens varied upon viral
      infection, which is also capable of inducing oxygen radicals. In particular we
      underline the relevant intracellular accumulation of ferritin that paralleled an
      increase of cell surface expression of the transferrin receptor. Evaluation of
      cellular events upon HCV infection in THP-1 cells may represent a useful tool
      with which to identify alteration in monocytes metabolism and to study
      therapeutic approaches for such alterations.

PMID- 15515126
TI  - Suicide gene therapy with an adenovirus expressing the fusion gene CD::UPRT in
      human glioblastomas: different sensitivities correlate with p53 status.
AB  - BACKGROUND: Several gene therapy strategies have been designed for cancer
      treatment. Intra-tumoral injection of adenoviruses expressing pro-drug-converting
      enzymes is one such strategy. Although the efficacy of these therapies was tested
      in animal models, little work has been devoted to the determination of critical
      variables for success. In this work, we aimed at better understanding variables
      that affect the cytosine deaminase::uracil phosphoribosyl transferase (CD::UPRT)
      based strategy in two human glioblastomas. METHODS: We have constructed two
      adenoviruses expressing either CD or the fusion protein CD::UPRT. We have tested
      their anti-tumor activity in combination with 5-fluorocytosine (5-FC) in the
      glioblastoma cell lines U87 and U251, which are p53-wt and p53-deficient,
      respectively. Anti-tumor activity has also been investigated in spheroid
      structures. RESULTS: The superiority of CD::UPRT over CD was confirmed in both
      glioblastoma cells. We found that the pro-drug concentration required for anti
      tumor activity was 9-fold higher in U251 than in U87, while multiplicity of
      infection (MOI) as low as 6 was sufficient to achieve 50% killing. Bystander
      activity was observed with as few as 2 and 6% transduced cells for U87 and U251,
      respectively. Differences in sensitivity between U87 and U251 were not due to
      differences in transduction, transgene expression, or intercellular transport,
      but were related to 5-FU sensitivity and p53 status. Also, it is noteworthy that,
      in contrast to U87, U251 spheroids barely responded to the treatment, whereas
      their monolayer counterparts were very sensitive. CONCLUSIONS: Our study has
      shown that p53 status is important for CD::UPRT/5-FC treatment. Moreover, this
      study demonstrated that the three-dimensional spheroid model is a more stringent
      in vitro model for suicide gene therapy evaluation than are monolayer cultures.

PMID- 15515127
TI  - Developing methods and strains for genetic studies in the Saccharomyces bayanus
      var. uvarum species.
AB  - For years, Saccharomyces cerevisiae has been used as a model organism to gain
      insight into complex biological processes. The study of closely related yeast
      species may be critical for understanding the molecular mechanism of evolution.
      Among those species, S. bayanus var. uvarum could be particularly pertinent
      because of the availability of its genome sequence. However, to date, in that
      species genetic studies are problematical due to the lack of standard strains
      collection and genetic methods. Here, we have developed heterothallic S. bayanus
      var. uvarum strains and obtained stable haploid strains. We further used UV
      induced mutation and gene disruption to create a collection of auxotrophic
      derivatives. Finally, we have elaborated or improved methods to cultivate cells,
      obtain zygotes and spores and to transform this species. All these tools can now
      be used by the scientific community to study the biology of this species.

PMID- 15515128
TI  - Comparison of three expression systems for heterologous xylanase production by S.
      cerevisiae in defined medium.
AB  - The influence of the auxotrophic deficiencies of the host strain and expression
      vector selection on the production of a heterologous protein was investigated.
      Heterologous xylanase production by two prototrophic S. cerevisiae transformants,
      containing either a plasmid-based, YEp-type expression system or an integrative,
      YIp-type expression system, were compared with production by an auxotrophic
      transformant, containing an identical YEp-type expression system, in batch and
      continuous cultivation, using a chemically defined medium. Heterologous xylanase
      production by the auxotrophic strains in defined medium was critically dependent
      on the availability of amino acids, as extracellular xylanase production
      increased dramatically when amino acids were over-consumed from the medium to the
      point of saturating the cell. Saturation with amino acids, indicated by an
      increased leakage of amino acids from the cell, was thus a prerequisite for high
      level of heterologous protein production by the auxotrophic strain. Maximal
      xylanase production levels by the auxotrophic strain corresponded to the levels
      obtained with a similar prototrophic strain during cultivation in defined medium
      without amino acids. Superfluous auxotrophic markers thus had a strong
      deleterious effect on heterologous protein production by recombinant yeasts, and
      the use of such strains should be limited to initial exploratory investigations.
      The increased copy number and foreign gene dosage of the YEp-based expression
      vector, stabilized by the ura3 fur1 autoselection system, significantly improved
      production levels of heterologous xylanase, compared to the YIp system, which is
      based on a single integration into the yeast genome. No evidence was found of the
      possible saturation of the host secretory capacity by multicopy overexpression.
      Stable production of heterologous xylanase at high levels by the prototrophic YEp
      based recombinant strain, compared to the YIp system, was demonstrated.

PMID- 15515129
TI  - The yeast rRNA biosynthesis factor Ebp2p is also required for efficient nuclear
      division.
AB  - Molecular genetic analysis of the yeast Ebp2 protein has revealed that it is an
      essential, nucleolar protein that functions in the rRNA biosynthesis pathway.
      Temperature-sensitive ebp2-1 mutants are defective in the processing of the 27 SA
      precursor rRNA, and the point substitutions that disrupt this activity cluster
      towards the central, more highly conserved region of the Ebp2 protein. We report
      here that other ebp2 mutants exhibit deficiencies associated with defects in
      chromosome segregation. Yeast cells bearing a 50 amino acid C-terminal truncation
      allele (ebp2 delta C50) display a slow-growth phenotype and exhibit an increased
      percentage of cells with the nucleus positioned at the bud neck. The ebp2-1 and
      ebp2 delta C50 alleles genetically complement each other, and ebp2 delta C50
      mutants exhibit nuclear division defects that are distinct from the rRNA
      biosynthesis-related phenotypes of ebp2-1 mutants. Cytological and FACS analysis
      of the ebp2 delta C50 deletion mutants indicate that the chromosome segregation
      related activities of the Ebp2 protein are monitored by Mad2p, a mitotic
      checkpoint protein. The finding that yeast Ebp2p functions in nuclear division is
      consistent with the growing body of evidence that supports the role that human
      EBP2 plays in chromosome segregation.

PMID- 15515130
TI  - Model-checking techniques for stratified case-control studies.
AB  - We present graphical and numerical methods for assessing the adequacy of the
      logistic regression model for stratified case-control data. The proposed methods
      are derived from the cumulative sum of residuals over the covariate or linear
      predictor. Under the assumed model, the cumulative residual process converges
      weakly to a zero-mean Gaussian process whose distribution can be approximated via
      Monte Carlo simulation. The observed cumulative residual pattern can then be
      compared both visually and analytically to a number of simulated realizations
      from the approximate null distribution. These comparisons enable one to examine
      the functional form of each covariate, the logistic link function as well as the
      overall model adequacy. Simulation studies demonstrate that the proposed methods
      perform well in practical settings. Illustration with an oesophageal cancer study
      is provided.

PMID- 15515131
TI  - Acute efficacy of a sublingual dose of nifedipine on uterine arterial blood flow:
      preliminary data in prematurely menopausal women.
AB  - OBJECTIVES: To determine whether the calcium blocker nifedipine alters Doppler
      velocimetry and impedance parameters in the uterine artery in prematurely
      menopausal women. METHODS: Uterine artery Doppler examinations were performed
      transvaginally in seventeen prematurely menopausal women without the use of
      calcium blocker (T0). Following a 10-mg sublingual dose of nifedipine patients
      were subsequently rescanned at successive time intervals (T25 = 25, T40 = 40, T60
      = 60 min). PI (normalized (NPI) for heart rate) and maximum, minimum and average
      velocities of the uterine artery were recorded and waveforms were qualitatively
      assessed using Goswamy and Steptoe's waveform classification. RESULTS:
      Quantitative analysis showed a significant decrease in NPI at T(25) in the right
      and left uterine arteries (T0: PI = 2.95 and 3.01; T25: PI = 1.52 and 1.52,
      respectively; P < 0.001) and until the end of the experiment. Minimum and average
      blood flow velocities increased strongly (P < 0.001) whereas the maximum
      velocities did not change significantly (P = 0.12). Qualitative analysis revealed
      more conspicuous results: eight subjects presented 'abnormal' spectra: one was
      type A (absence of protodiastole), three were type B (absence of telediastole)
      and four were type O (no diastolic blood flow); all of them recovered type C
      waveforms (normal spectrum) during the hour following nifedipine administration.
      CONCLUSIONS: Nifedipine induces a reversible decrease in NPI and an increase in
      blood flow velocities in the uterine artery in prematurely menopausal women.
      These results suggest that nifedipine is a potent uterine arterial vasodilator.

PMID- 15515132
TI  - On linear combinations of biomarkers to improve diagnostic accuracy.
AB  - We consider combining multiple biomarkers to improve diagnostic accuracy. Su and
      Liu derived the linear combinations that maximize the area under the receiver
      operating characteristic (ROC) curves. These linear combinations, however, may
      have unsatisfactory low sensitivity over a certain range of desired specificity.
      In this paper, we consider maximizing sensitivity over a range of specificity. We
      first present a simpler proof for Su and Liu's main theorem and further
      investigate some other optimal properties of their linear combinations. We then
      derive alternative linear combinations that have higher sensitivity over a range
      of high (or low) specificity. The methods are illustrated using data from a study
      evaluating biomarkers for coronary heart disease.

PMID- 15515133
TI  - Gene electro-transfer of an improved erythropoietin plasmid in mice and non-human
      primates.
AB  - BACKGROUND: Anemia due to impaired erythropoietin (EPO) production is associated
      with kidney failure. Recombinant proteins are commonly administered to alleviate
      the symptoms of this dysfunction, whereas gene therapy approaches envisaging the
      delivery of EPO genes have been tried in animal models in order to achieve stable
      and long-lasting EPO protein production. Naked DNA intramuscular injection is a
      safe approach for gene delivery; however, transduction levels show high inter
      individual variability in rodents and very poor efficiency in non-human primates.
      Transduction can be improved in several animal models by application of electric
      pulses after DNA injection. METHODS: We have designed a modified EPO gene version
      by changing the EPO leader sequence and optimizing the gene codon usage. This
      modified gene was electro-injected into mice, rabbits and cynomolgus monkeys to
      test for protein production and biological effect. CONCLUSIONS: The modified EPO
      gene yields higher levels of circulating transgene product and a more significant
      biological effect than the wild-type gene in all the species tested, thus showing
      great potential in clinically developable gene therapy approaches for EPO
      delivery.

PMID- 15515134
TI  - A permutation test for inference in logistic regression with small- and moderate
      sized data sets.
AB  - Inference based on large sample results can be highly inaccurate if applied to
      logistic regression with small data sets. Furthermore, maximum likelihood
      estimates for the regression parameters will on occasion not exist, and large
      sample results will be invalid. Exact conditional logistic regression is an
      alternative that can be used whether or not maximum likelihood estimates exist,
      but can be overly conservative. This approach also requires grouping the values
      of continuous variables corresponding to nuisance parameters, and inference can
      depend on how this is done. A simple permutation test of the hypothesis that a
      regression parameter is zero can overcome these limitations. The variable of
      interest is replaced by the residuals from a linear regression of it on all other
      independent variables. Logistic regressions are then done for permutations of
      these residuals, and a p-value is computed by comparing the resulting likelihood
      ratio statistics to the original observed value. Simulations of binary outcome
      data with two independent variables that have binary or lognormal distributions
      yield the following results: (a) in small data sets consisting of 20
      observations, type I error is well-controlled by the permutation test, but poorly
      controlled by the asymptotic likelihood ratio test; (b) in large data sets
      consisting of 1000 observations, performance of the permutation test appears
      equivalent to that of the asymptotic test; and (c) in small data sets, the p
      value for the permutation test is usually similar to the mid-p-value for exact
      conditional logistic regression.

PMID- 15515135
TI  - Lipid-mediated siRNA delivery down-regulates exogenous gene expression in the
      mouse brain at picomolar levels.
AB  - BACKGROUND: Efficient in vivo vectors are needed to exploit the enormous
      potential of RNA interference (RNAi). Such methods require optimisation for
      specific delivery routes, tissues and usages. We tested the capacity of different
      non-viral vectors and formulation methods for inhibition of exogenous
      (luciferase) gene expression when used to introduce small interfering RNA (siRNA)
      into the mouse brain in vivo. METHODS: Polyethylenimine (PEI)-based polyplexes
      and JetSI (a mixture of cationic lipids)-based lipoplexes were used to vectorise
      plasmid DNA encoding the firefly Photinus pyralis luciferase gene and picomolar
      amounts of siRNA directed against this gene. Two controls were used, DNA encoding
      an unrelated luciferase from Renilla reniformis and a mutated siRNA sequence.
      RESULTS: First, we found that linear PEI, although efficient for delivering
      nucleic acids to cells, did not permit development of siRNA activity within the
      dose range tested (<0.5 pmol). Second, various combinations of cationic lipids
      were tried and the best formulation was found to be a combination of JetSI with
      the fusogenic lipid dioleoylphosphatidylethanolamine (DOPE). Efficient inhibition
      of target, firefly luciferase was obtained with exceedingly low amounts of siRNA:
      78 +/- 6% inhibition at 24 h post-transfection with 0.2 pmol siRNA. This
      inhibition was dose-dependent and specific. No effect was seen on the control
      gene, co-transfected Renilla luciferase, and the control mutated siRNA sequence
      had no effect on the targeted firefly luciferase. CONCLUSIONS: We have optimised
      an efficient cationic lipoplex method for delivery of siRNA into the newborn
      mouse brain. Specific inhibition of exogenous target gene expression is obtained
      with picomolar amounts of siRNA.

PMID- 15515136
TI  - Characterization of a semi-replicative gene delivery system allowing propagation
      of complementary defective retroviral vectors.
AB  - BACKGROUND: Recently, several cancer gene therapy studies have shown that
      replication-competent retroviral vectors represent a major improvement over
      replication-defective ones in terms of transgene propagation efficiency. However,
      this positive effect is somewhat spoiled by the increased risk of dissemination
      and oncogenesis that replication-competent retroviral vectors entail. To enhance
      both their integral safety and their transgene capacity, we developed a semi
      replication-competent retroviral vector system. METHODS: The semi-replication
      competent retroviral vector system is based on two transcomplementing replication
      defective retroviral vectors termed gag-pol vector (GPv) and env vector (Ev).
      Vector propagation was monitored in vitro and in solid tumors in vivo, using
      different reporter transgenes for GPv and Ev. Systemic vector dissemination and
      leukemogenesis was assessed by direct intravenous vector injection and subsequent
      bone marrow transplantation, in MLV-sensitive mice. RESULTS: In vitro and in vivo
      the semi-replication-competent retroviral vectors propagate transgenes almost as
      efficiently as replication-competent ones. The semi-replication-competent
      retroviral vector system does not lead to detectable dissemination or
      leukemogenesis as does the replication-competent vector or the parental virus.
      Additionally, the vector duo allows co-propagation of different transgenes as
      well as mobilization of a third replication-defective vector. CONCLUSIONS: This
      study is an initial proof of principle for the use of complementary retroviral
      vectors to deliver and propagate transgenes in vitro and in solid tumors in vivo,
      but with reduced pathogenicity compared to its parental virus. In-between
      replication-defective and replication-competent retroviral vectors, this semi
      replicative system offers good grounds for its application in in vitro studies
      and allows envisioning its further development for cancer gene therapy.

PMID- 15515137
TI  - Regression methods for cost-effectiveness analysis with censored data.
AB  - A system of seemingly unrelated regression equations is proposed for prognostic
      factor adjustment and subgroup analysis when comparing two groups in a cost
      effectiveness analysis with censored data. Because of the induced dependent
      censoring on costs and quality-adjusted survival, inverse probability weighting
      is employed for parameter estimation. The method is illustrated with data from
      two recent examples using both survival time and quality-adjusted survival time
      as the measures of effectiveness.

PMID- 15515138
TI  - Bayesian tests of extra-Binomial variability.
AB  - A simple model for extra-Binomial variability is the Beta-Binomial. A
      complication in testing the Binomial against the Beta-Binomial alternative is
      that the Binomial lies on the boundary of the Beta-Binomial, which forces
      modifications to the usual asymptotic arguments. In this paper, we propose a
      Bayesian test using a pair of approximate Bayes factors, one for the case in
      which the maximum likelihood estimator (MLE) of the extra-Binomial variability is
      zero and one for the case in which it is positive. These approximate Bayes
      factors are easy to compute. We evaluate the operating characteristics of the
      Bayes factors and find them to be more powerful than the likelihood ratio test.
      We then apply the method to three data sets, including one in which the issue is
      whether a logistic regression intercept should be considered a random effect. In
      each case, our approximate Bayes factors are close to the exact Bayes factors,
      which may also be computed with additional effort.

PMID- 15515139
TI  - Transduction of satellite cells after prenatal intramuscular administration of
      lentiviral vectors.
AB  - BACKGROUND: We have previously reported long-term expression of lacZ in myocytes
      after in utero intramuscular injection of Mokola and Ebola pseudotyped lentiviral
      vectors. In further experiments, we have noted that these vectors also transduce
      small cells at the periphery of the muscle fibers that have the morphology of
      satellite cells, or muscle stem cells. In this study we performed experiments to
      further define the morphology and function of these cells. METHODS: Balb/c mice
      at 14-15 days gestation were injected intramuscularly with Ebola or Mokola
      pseudotyped lentiviral vectors carrying CMV-lacZ. Animals were harvested at
      various time points, muscles were stained with X-gal, and processed for electron
      microscopy (EM) and immunofluorescence. To determine whether transduced satellite
      cells were functionally capable of regenerating injured muscles, animals were
      injected with notexin in the same area 8 weeks after the in utero injection of
      viral vector. RESULTS: Transmission EM of transduced cells confirmed the
      ultrastructural appearance of satellite cells. Double immunofluorescence for beta
      galactosidase and satellite cell markers demonstrated co-localization of these
      markers in transduced cells. In the notexin-injured animals, small blue cells
      were seen at the areas of regeneration that co-localized beta-galactosidase with
      markers of regenerating satellite cells. Central nucleated blue fibers were seen
      at late time points, indicating regenerated muscle fibers arising from a
      transduced satellite cell. CONCLUSIONS: This study demonstrates transduction of
      muscle satellite cells following prenatal viral vector mediated gene transfer.
      These findings may have important implications for gene therapy strategies
      directed toward muscular dystrophy.

PMID- 15515140
TI  - Gene expression and immune response kinetics using electroporation-mediated DNA
      delivery to muscle.
AB  - BACKGROUND: Injection of DNA encoding exogenic proteins into muscle tissue
      combined with electroporation often results in a transient increase of the
      encoded protein concentration in the muscle and the blood. The reduction is
      normally due to an immune response against the exogenic protein but other factors
      may also be involved. How various electroporation parameters affect the
      concentration kinetics of syngenic and exogenic proteins is studied in relation
      to immune response and muscle damage after electroporation-mediated DNA transfer
      to muscle. METHODS: Electroporation was applied to mouse quadriceps and rat
      tibialis anterior muscles after injection of DNA encoding either secreted
      alkaline phosphatase (SEAP), beta-galactosidase (beta-gal), luciferase or a mouse
      IgG molecule. Protein concentrations in blood or muscle and antibody responses
      were measured for a period up to 3 months. Tissue inflammation and muscle cell
      damage were studied on muscle cross-sections and assessed by measuring the
      concentrations of creatine phosphokinase (CPK) in blood. RESULTS: Mice with the
      highest SEAP concentration in blood at day 7 also had the highest rate of
      decrease afterwards, the strongest antibody responses against SEAP and the
      highest acute levels of CPK in blood. DNA-transfected muscle fibers were
      significantly reduced in number from days 7 to 14. Mononuclear cells surrounded
      the reporter gene expressing muscle fibers, thus indicating a cellular immune
      response. When using DNA encoding a syngenic protein the protein concentration in
      blood was relatively stabile over a 3-month period, but showed different kinetics
      for various electroporation parameters. CONCLUSIONS: Our findings suggest that
      the optimal electroporation parameters for DNA vaccination may be different from
      the optimal parameters for long-term expression of genes encoding syngenic
      proteins.

PMID- 15515141
TI  - In vivo anti-tumour activity of recombinant MVM parvoviral vectors carrying the
      human interleukin-2 cDNA.
AB  - BACKGROUND: The natural oncotropism and oncotoxicity of vectors derived from the
      autonomous parvovirus, minute virus of mice (prototype strain) [MVM(p)], combined
      with the immunotherapeutic properties of cytokine transgenes, make them
      interesting candidates for cancer gene therapy. METHODS: The in vivo anti-tumour
      activity of a recombinant parvoviral vector, MVM-IL2, was evaluated in a
      syngeneic mouse melanoma model that is relatively resistant in vitro to the
      intrinsic cytotoxicity of wild-type MVM(p). RESULTS: In vitro infection of the
      K1735 melanoma cells prior to their injection resulted in loss of tumorigenicity
      in 70% of mice (7/10). Tumour-free mice were protected against a challenge with
      non-infected parental cells. In addition, MVM-IL2-infected tumour cells induced
      an anti-tumour activity on parental cells injected at a distant location. These
      non-infected tumour cells were injected either at the same time or 7 days before
      the injection of MVM-IL2-infected cells. In the latter setting, which mimics a
      therapeutic model for small tumours, 4/10 mice were still tumour-free after 4
      months. CONCLUSIONS: Our results show that (i) the MVM-IL2 parvoviral vector
      efficiently transduces tumour cells; and (ii) the low multiplicity of infection
      (MOI = 1) used in our experiments was sufficient to elicit an anti-tumour effect
      on distant cells, which supports further studies on this vector as a new tool for
      cancer gene therapy.

PMID- 15515142
TI  - The use of amino acids to enhance the aerosolisation of spray-dried powders for
      pulmonary gene therapy.
AB  - BACKGROUND: Pulmonary delivery of gene therapy offers the potential for the
      treatment of a range of lung conditions, including cystic fibrosis, asthma and
      lung cancer. Spray-drying may be used to prepare dry powders for inhalation;
      however, aerosolisation of such powders is limited, resulting in poor lung
      deposition and biological functionality. In this study, we examine the use of
      amino acids (arginine, aspartic acid, threonine, phenylalanine) to enhance the
      aerosolisation of spray-dried powders containing model non-viral gene vectors.
      METHODS: Lipid/polycation/pDNA (LPD) vectors, in the presence or absence of amino
      acids, were dispersed in lactose solutions, and spray-dried to produce
      appropriately sized dry powders. Scanning electron microscopy and laser
      diffraction were used to determine particle morphology and diameter,
      respectively. Gel electrophoresis was used to examine the influence of amino
      acids on the structural integrity of the LPD complex. In vitro cell (A549)
      transfection was used to determine the biological functionality of the dry
      powders, and the in vitro aerosolisation performance was assessed using a
      multistage liquid impinger (MSLI). RESULTS: Both gel electrophoresis and in vitro
      cell transfection indicated that certain amino acids (aspartic acid, threonine)
      can adversely affect the integrity and biological functionality of the LPD
      complex. All amino acids significantly increased the aerosolisation of the
      powder, with the arginine and phenylalanine powders showing optimal deposition in
      the lower stages of the MSLI. CONCLUSIONS: Amino acids can be used to enhance the
      aerosolisation of spray-dried powders for respiratory gene delivery, allowing the
      development of stable and viable formulations for pulmonary gene therapy.

PMID- 15515143
TI  - Glycogen storage in multiple muscles of old GSD-II mice can be rapidly cleared
      after a single intravenous injection with a modified adenoviral vector expressing
      hGAA.
AB  - BACKGROUND: Glycogen storage disease II (GSD-II) is an autosomal recessive
      lysosomal storage disease, due to acid-alpha-glucosidase (GAA) deficiency. The
      disease is characterized by massive glycogen accumulation in the cardiac and
      skeletal muscles. There is early onset (infantile, also known as Pompe disease)
      as well as late onset (juvenile and adult) forms of GSD-II. Few studies have been
      published to date that have explored the consequences of delivering a potential
      therapy to either late onset GSD-II subjects, and/or early onset patients with
      long-established muscle pathology. One recent report utilizing GAA-KO mice
      transgenically expressing human GAA (hGAA) suggested that long-established
      disease in both cardiac and skeletal muscle is likely to prove resistant to
      therapies. To investigate the potential for disease reversibility in old GSD-II
      mice, we studied their responsiveness to exogenous hGAA exposure via a gene
      therapy approach that we have previously shown to be efficacious in young GAA-KO
      mice. METHODS: An [E1-, polymerase-] adenoviral vector encoding hGAA was
      intravenously injected into two groups of aged GAA-KO mice; GAA expression and
      tissue glycogen reduction were evaluated. RESULTS: After vector injection, we
      found that extremely high amounts of hepatically secreted hGAA could be produced,
      and subsequently taken up by multiple muscle tissues in the old GAA-KO mice by 17
      days post-injection (dpi). As a result, all muscle groups tested in the old GAA
      KO mice showed significant glycogen reductions by 17 dpi, relative to that of age
      matched, but mock-injected GAA-KO mice. For example, glycogen reduction in heart
      was 84%, in quadriceps 46%, and in diaphragm 73%. Our data also showed that the
      uptake and the subsequent intracellular processing of virally expressed hGAA were
      not impaired in older muscles. CONCLUSIONS: Overall, the previously reported
      'resistance' of old GAA-KO muscles to exogenous hGAA replacement approaches can
      be rapidly overcome after a single intravenous injection with a modified
      adenoviral vector expressing hGAA.

PMID- 15515144
TI  - Adenovirus binding to cultured synoviocytes triggers signaling through MAPK
      pathways and induces expression of cyclooxygenase-2.
AB  - BACKGROUND: Recombinant adenovirus can be administered in vivo to achieve
      transduction of a number of cell types including human synoviocytes.
      Immunogenicity of adenoviruses has limited their utility as vectors for gene
      delivery; however, specific mechanisms underlying the acute inflammatory response
      to adenovirus are not well understood. Activation of a number of signal
      transduction pathways occurs rapidly upon adenovirus binding to cell-surface
      receptors. We investigated stimulated expression of mitogen-activated protein
      kinases (MAPKs), cyclooxygenase-2 (COX-2) and prostaglandin E(2) (PGE(2)) in
      human primary synovial fibroblasts to adenovirus expressing the E. coli beta
      galactosidase gene. METHODS: Cultured rheumatoid synoviocytes were exposed to
      transduction-competent Ad/RSVlacZ recombinant adenovirus or transduction
      incompetent (psoralen/UV-irradiated) Ad/RSVlacZ. The effects on COX-2 expression,
      PGE(2) levels and MAPK signaling in synoviocytes were assessed using a
      combination of reverse-transcription polymerase chain reaction amplification and
      immunoblotting. RESULTS: Adenovirus treatment of synoviocytes increased levels of
      COX-2 mRNA and protein as well as PGE(2). Psoralen-treated transcriptionally
      inactive adenovirus was equivalent to untreated adenovirus for early COX-2
      induction suggesting that viral genes were not required. Adenovirus treatment
      stimulated phosphorylation of ERK-1/-2, p38 MAPK, and JNK. Inhibition of the ERK
      and p38 MAPK pathways inhibited COX-2 expression and PGE(2) production.
      CONCLUSIONS: Taken together, these data demonstrate that a MAPK-dependent
      increase in COX-2 results in local prostaglandin production. These findings have
      clinical implications for use of adenovirus as vectors for in vivo gene delivery.

PMID- 15515145
TI  - Toroid formation in charge neutralized flexible or semi-flexible biopolymers:
      potential pathway for assembly of DNA carriers.
AB  - BACKGROUND: The theoretical state diagram for semi-flexible macromolecules such
      as DNA predicts that a tightly wound toroid can be a stable structure.
      Experimentally, toroids roughly 100 nm in diameter are routinely observed for DNA
      in the presence of multivalent cations at low DNA concentration. Theory also
      predicts toroids can form between non-DNA semi-flexible polymers and multivalent
      counterions. This phenomenon provides a means to co-package DNA with
      functionalized anionic polymers to create gene delivery systems. METHODS AND
      RESULTS: We show using electron microscopy that non-DNA polymers (polylysine,
      polyglutamic acid, and dextran sulfate) form toroids when mixed with multi- or
      polyvalent ions of opposite charge. The non-DNA toroids are similar in diameter
      to ones made with DNA. The results using dextran sulfate, a semi-flexible
      polymer, are explained by current theory. However, theory predicts that high
      flexibility in polypeptides should discourage their incorporation into stable
      toroids. To explain these latter observations we propose that charge
      neutralization facilitates secondary structure formation, which confers
      stiffness, thereby allowing stable toroids for the polypeptides studied. We
      measured the secondary structure of the toroid-forming polypeptides using
      circular dichroism (CD). The CD spectrum indicates the polypeptides undergo
      transitions from non-ordered structures (random coil) to ordered secondary
      structures (either alpha-helix or beta-sheet) upon charge neutralization which
      supports the hypothesis. The type of secondary structure is dependent on the type
      of multivalent counterion used to form the toroids. Formation of the polypeptide
      toroids confers resistance to heat denaturation of the resulting polypeptide
      secondary structure. The CD spectrum of DNA in a toroid also is changed from that
      of uncomplexed DNA, but all of the counterions used to form DNA toroids created
      structures with similar CD spectra in the DNA region (250-290 nm). CONCLUSIONS:
      The toroid structure obtained using DNA is observed in other semi-flexible non
      DNA polymers such as dextran sulfate, and also in flexible polymers such as
      polylysine and polyglutamic acid upon charge neutralization with multivalent
      counterions. In the flexible polymers we propose that this phenomenon is due to
      induction of secondary structure upon charge neutralization, which decreases
      polymer flexibility, i.e. increases polymer stiffness, to enable toroid
      formation. These results have significant implications for the co-assembly of non
      DNA anionic polymers with DNA to create nanoscopic gene carriers.

PMID- 15515146
TI  - Use of a murine secreted alkaline phosphatase as a non-immunogenic reporter gene
      in mice.
AB  - BACKGROUND: The development of any vector system as a gene delivery system
      requires its optimization in vitro and in vivo. Preliminary studies frequently
      involve the use of a reporter gene, which allows for the rapid and simple assay
      of vector function through monitoring expression levels of the reporter gene.
      However, evaluation of vector efficacy can be compromised by immune responses
      directed against immunogenic reporter proteins. METHODS: We have cloned a murine
      secreted alkaline phosphatase (mSEAP), and explored its use as a reporter gene in
      the context of an early region 1 (E1)-deleted adenovirus (Ad) vector. Studies
      involved characterization of gene expression in vitro and in vivo, and
      immunological responses after gene delivery to mice. RESULTS: In tissue culture,
      we show that mSEAP is easily measured quantitatively using a sensitive,
      commercially available chemiluminescent assay, or visualized directly using
      histological staining. The level of transgene expression from AdmSEAP was similar
      to that observed for an Ad vector encoding the human placental secreted alkaline
      phosphatase (hSEAP). After intravenous administration in mice, AdmSEAP continued
      to express at high levels for the duration of the experiment (1 month), whereas
      expression from AdhSEAP declined to background levels over the course of the
      experiment. Although cytotoxic T-lymphocytes were not detected against either the
      murine or human SEAP proteins in mice, antibodies were readily detected against
      the human protein. No antibodies were detected to mSEAP. CONCLUSIONS: Taken
      together, these data illustrate that mSEAP is a sensitive, non-immunogenic
      reporter gene for preclinical mouse studies.

PMID- 15515148
TI  - An efficient gene transfer method mediated by ultrasound and microbubbles into
      the kidney.
AB  - BACKGROUND: Safety issues are of paramount importance in clinical human gene
      therapy. From this point of view, it would be better to develop a novel non-viral
      efficient gene transfer method. Recently, it was reported that ultrasound
      exposure could induce cell membrane permeabilization and enhance gene expression.
      METHODS: In this study, we examined the potential of ultrasound for gene transfer
      into the kidney. First, we transfected rat left kidney with luciferase plasmid
      mixed with microbubbles, Optison, to optimize the conditions (duration of
      ultrasound and concentration of Optison). Then, 4, 7, 14 and 21 days after gene
      transfer, luciferase activity was measured. Next, localization of gene expression
      was assessed by measuring luciferase activity and green fluorescent protein (GFP)
      expression. Expression of GFP plasmid was examined under a fluorescence
      microscope at 4 and 14 days after gene transfer. Finally, to examine the side
      effects of this gene transfer method, biochemical assays for aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN)
      and creatinine (Cre) were performed. RESULTS: Optison and/or ultrasound
      significantly enhanced the efficiency of gene transfer and expression in the
      kidney. Especially, 70-80% of total glomeruli could be transfected. Also, a
      significant dose-dependent effect of Optison was observed as assessed by
      luciferase assay (Optison 25%: 12.5 x 10(5) relative light units (RLU)/g tissue;
      50%: 31.3 x 10(5) RLU/g tissue; 100%: 57.9 x 10(5) RLU/g tissue). GFP expression
      could be observed in glomeruli, tubules and interstitial area. Results of blood
      tests did not change significantly after gene transfer. CONCLUSIONS: Overall, an
      ultrasound-mediated gene transfer method with Optison enhanced the efficiency of
      gene transfer and expression in the rat kidney. This novel non-viral method may
      be useful for gene therapy for renal disease.

PMID- 15515150
TI  - Assessing surrogates as trial endpoints using mixed models.
AB  - Having a surrogate for a definitive endpoint in a clinical trial can sometimes be
      useful when it is impractical, invasive or very time consuming to obtain the
      definitive endpoint. This paper discusses methods for assessing whether the
      surrogate-endpoint results of a trial can be used in place of definitive-endpoint
      results. It is important when examining this trial-level surrogacy to include the
      possibility of trial-level effects and to distinguish whether the treatment arms
      are naturally ordered, e.g. A vs A+B rather than A vs B. Methods using mixed
      models of trial-level summaries are discussed and compared to fixed-effects
      models and to the possibility of using models of individual-level data. We give
      estimators for definitive-endpoint results of a trial that are predicted from the
      surrogate-endpoint results of the trial and a set of results from previous trials
      in which both the definitive and surrogate trial results were available.
      Graphical displays are also suggested. Two sets of trial results previously
      analysed for trial-level surrogacy are used as examples.

PMID- 15515149
TI  - Low-pH-sensitive poly(ethylene glycol) (PEG)-stabilized plasmid
      nanolipoparticles: effects of PEG chain length, lipid composition and assembly
      conditions on gene delivery.
AB  - BACKGROUND: We have studied the effects of the poly(ethylene glycol) (PEG) chain
      length and acyl chain composition on the pH-sensitivity of acid-labile PEG
      diorthoester (POD) lipids. The optimal conditions are described for preparation
      of DNA plasmid encapsulated POD nanolipoparticles (NLPs) which mediate high gene
      delivery activity in vitro with moderate cytotoxicity. METHODS AND RESULTS: A
      series of POD lipids with various PEG chain lengths (750, 2000, and 5000 Da) or
      acyl chains (distearoyl 18:0 or dioleoyl 18:1) were incorporated into DNA
      containing NLPs or model liposomes as a stealth and bioresponsive component. We
      investigated the collapse kinetics of the POD-stabilized liposomes when the PEG
      chain length was changed. We optimized a detergent dialysis method to encapsulate
      plasmid DNA into NLPs prepared from a mixture of the various POD lipids, cationic
      lipid and phosphatidylethanolamine lipid. A critical concentration (28 mM) of n
      octyl-beta-D-glucopyranoside (OG) enabled high encapsulation of DNA plasmid into
      100 nm particles with a neutral surface charge. The POD NLPs are stable at pH 8.5
      but rapidly collapse (approximately 10 min) into aggregates at pH 5.0. In the
      detergent solution there is a metastable DNA-lipid intermediate that evolves into
      a stable NLP if the detergent is removed shortly after adding DNA to the lipid
      detergent mixture. The rank order of transfection activity from NLPs containing
      PEG-lipid was POD 750 > POD 5000 = POD 2000 > non-pH-sensitive PEG-lipid. The
      particle size stability was in the reverse order. Binding of the NLPs to cells
      reached a maximum level by 12 hours. The POD NLPs had slightly less transfection
      activity but considerably lower cytotoxicity than the PEI-DNA polyplex.
      CONCLUSIONS: Of the PEG-orthoester lipids tested, POD 2000 is the better choice
      for the preparation of sterically stabilized NLPs with a small particle diameter,
      good stability, low cytotoxicity, and satisfactory transfection activity.

PMID- 15515151
TI  - More powerful two-sample tests for differences in repeated measures of adverse
      effects in psychiatric trials when only some patients may be at risk.
AB  - Common adverse effect measures in psychiatric trials are typically analysed with
      repeated measures ANOVA, despite having distributions which violate key
      assumptions of that method; moreover, some adverse effects may be concentrated in
      vulnerable subgroups of participants. For testing treatment differences in
      adverse effects, we propose use of Kendall's taub as a summary measure of within
      participant trends in adverse events, in conjunction with a weighted modification
      of a rank test proposed by Conover and Salsburg. Data on extrapyramidal side
      effects from a controlled clinical trial conducted in persons with treatment
      resistant schizophrenia was used to compare the proposed analysis to repeated
      measures ANOVA using mixed models and alternate tests for treatment differences
      in taub trend scores.

PMID- 15515152
TI  - Sense and sensitivity when correcting for observed exposures in randomized
      clinical trials.
AB  - Standard intent-to-treat analyses of randomized clinical trials can yield biased
      estimates of treatment efficacy and toxicity when not all patients comply with
      their assigned treatment. Flexible methods have been proposed which correct for
      this by modelling expected contrasts between an individual's observed outcome and
      his/her potential outcome in the absence of exposure. Because such comparisons
      often require untestable assumptions, a sensitivity analysis is warranted. We
      show how this can be performed in a meaningful and practically useful way.
      Following the approach of Molenberghs, Kenward and Goetghebeur in a missing data
      context, we evaluate the separate contributions of structural uninformativeness
      and sampling variation to uncertainty about the population parameters. This leads
      us to consider Honestly Estimated Ignorance Regions (HEIRs) and Estimated
      Uncertainty RegiOns (EUROs), respectively. We use the results to estimate the
      causal effect of observed exposure on successful blood pressure reduction in a
      randomized controlled clinical trial with partial non-compliance.

PMID- 15515153
TI  - Multiple testing procedures based on weighted Kaplan-Meier statistics for right
      censored survival data.
AB  - In clinical trials or drug development studies, researchers are often interested
      in identifying which treatments or dosages are more effective than the standard
      one. Recently, several multiple testing procedures based on weighted logrank
      tests have been proposed to compare several treatments with a control in a one
      way layout where survival data are subject to random right-censorship. However,
      weighted logrank tests are based on ranks, and these tests might not be sensitive
      to the magnitude of the difference in survival times against a specific
      alternative. Therefore, it is desirable to develop a more robust and powerful
      multiple testing procedure. This paper proposes multiple testing procedures based
      on two-sample weighted Kaplan-Meier statistics, each comparing an individual
      treatment with the control, to determine which treatments are more effective than
      the control. The comparative results from a simulation study are presented and
      the implementation of these methods to the prostate cancer clinical trial and the
      renal carcinoma tumour study are presented.

PMID- 15515154
TI  - Effect of vanillin on toxicant-induced mutation and mitotic recombination in
      proliferating somatic cells of Drosophila melanogaster.
AB  - Vanillin (VA; C8H8O3) is a flavoring agent that in previous studies has both
      increased and decreased the genotoxicity of chemical agents, depending on the
      nature of both the agent and the genetic event measured. The ability of VA to
      modulate the mutagenicity and recombinogenicity of three different monoalkylating
      agents, N-ethyl-N-nitrosourea (ENU), N-methyl-N-nitrosourea (MNU), and ethyl
      methanesulfonate (EMS), and the intercalating agent bleomycin (BLEO) was examined
      using the somatic mutation and recombination test (SMART) in Drosophila
      melanogaster. While neither the mutagenicity nor the recombinagenicity of ENU or
      MNU was modified by posttreatment with VA, EMS-induced genetic toxicity was
      enhanced by as much as 30%. This overall enhancement included a synergistic
      increase in mitotic recombination and a lesser decrease in mutation.
      Posttreatment with VA also produced an increase in the genotoxicity of BLEO,
      which was characterized by increases of 120% and 180% for 0.5% and 1% VA,
      respectively. This enhancement was restricted to an increase in recombinational
      events, since no alteration in BLEO-induced mutation was observed. The data
      suggest that the major VA-modulatory action on genotoxicity in D. melanogaster is
      related to its synergistic effects on somatic recombination, which has a greater
      consequence on overall genotoxicity than its antimutagenic effects. Since the
      SMART assay is specifically sensitive to mitotic crossing-over, our data suggest
      that VA promotes toxicant-induced homologous recombination, at least in the
      proliferative cells of Drosophila.

PMID- 15515155
TI  - Use of modified Northwick Park Neck Pain Questionnaire in patients with
      postirradiation neck disability: validation study.
AB  - BACKGROUND: No available measure exists for postirradiation neck disability.
      Adoption of the Chinese Northwick Park Neck Pain Questionnaire (NPQ) for patients
      with postirradiation neck disability was examined in this study. METHODS: Eight
      physiotherapists and five patients were invited to test the validity of the
      content. Forty-three patients with neck disability were recruited to evaluate
      test-retest reliability and internal consistency. The level of neck discomfort,
      range of neck motion and maximal isometric neck muscle strength, and SF-36 health
      score were measured for construct validity testing. RESULTS: The questionnaire
      had good content validity, a high degree of test-retest reliability, internal
      consistency (intraclass correlation coefficient [ICC], 0.94; Cronbach's alpha,
      0.88), and good construct validity. NPQ correlated significantly with most of the
      subscores of SF-36 (r(s), -0.43 to - 0.71) and numeric rating scale (r(s) =
      0.69). CONCLUSION: The modified Chinese NPQ was found to be reliable and valid
      for the evaluation of postirradiation neck disability.

PMID- 15515156
TI  - Surgeons' and nurses' use of e-mail communication with head and neck cancer
      patients.
AB  - BACKGROUND: "Telephone tag" for questions about postoperative symptoms and other
      concerns often engenders dissatisfaction. E-mail use may improve communication
      between patients and clinicians. This study aimed to describe surgeons' and
      nurses' use of E-mail with patients and their caregivers after head and neck
      cancer surgery. METHODS: We conducted a cross-sectional national survey of head
      and neck nurses and surgeons. RESULTS: Ninety-six percent of surgeon and 87% of
      nurse respondents used E-mail, but only 40% and 25%, respectively, used it with
      patients. More than 50% of both clinician groups that used E-mail with patients
      have done so for 2 to 5 years and began this practice at the request of patients.
      Surgeons not using E-mail with patients were twice as likely as nurses to cite
      privacy and liability issues, as well as time management and miscommunication
      concerns. CONCLUSIONS: Some clinicians use E-mail with patients, most often by
      patient request. Medicolegal and clinical ramifications require further study.

PMID- 15515157
TI  - TIMP1 and SERPIN-A overexpression and TFF3 and CRABP1 underexpression as
      biomarkers for papillary thyroid carcinoma.
AB  - BACKGROUND: No molecular pathways or specific genes are consistently associated
      with sporadic cases of papillary thyroid carcinoma (PTC), despite that it is the
      most common thyroid malignancy. Nodular goiter is an enlargement of the thyroid
      that is a compensatory response to a perturbation in normal thyroid homeostasis.
      It has been disputed in the literature that patients presenting with goiter have
      a higher incidence of PTC. The identification of molecular events that are common
      to both goiter and PTC could explain the overlap of these two disorders. METHODS:
      We used high-density oligonuleotide arrays to perform molecular profiling of PTC
      and nodular goiter with paired normal samples. RESULTS: Specifically, increased
      expression of SERPIN-A (proteinase inhibitor-alpha antitrypsin) and TIMP 1
      (tissue inhibitor of metalloproteinase 1) identified these as candidate molecular
      biomarkers for PTC. Decreases in the CRABP1 (cellular retinoic acid binding
      protein 1) and TFF3 (trefoil factor 3) expression levels identified these as
      candidate molecular biomarkers as well. The same analysis was performed to
      identify genes showing specific alterations in goiter tissues. CONCLUSIONS: This
      is the first report to our knowledge that compares the gene expression profiles
      of PTC and goiter. Our results suggest that PTC and goiter share very limited
      overlap in transcript expression.

PMID- 15515158
TI  - Induction chemotherapy with cisplatin and 5-fluorouracil followed by
      chemoradiotherapy or radiotherapy alone in the treatment of locoregionally
      advanced resectable cancers of the larynx and hypopharynx: results of single
      center study of 45 patients.
AB  - BACKGROUND: Induction chemotherapy with cisplatin and fluorouracil and
      radiotherapy is an effective alternative to surgery in patients with carcinoma of
      the larynx and hypopharynx who are treated for organ preservation. METHODS: We
      designed a protocol to evaluate the possibility of organ preservation in patients
      with advanced, resectable carcinoma of the larynx and hypopharynx. Forty-five
      eligible patients who were followed up between April 1999 and May 2001 were
      enrolled. Initially, these patients were treated with two cycles of induction
      chemotherapy consisting of cisplatin, 20 mg/m2/day on days 1 to 5, and 5
      fluorouracil, 600 mg/m2/day by continuous infusion on days 1 to 5. Patients who
      had a complete response to chemotherapy were treated with definitive
      radiotherapy; patients who had a partial response to chemotherapy were treated
      with chemoradiotherapy. Cisplatin, 35 mg/m2/week, was introduced throughout the
      duration of radiotherapy. Patients who had no response or progressive disease
      underwent surgery with postoperative radiotherapy. Patients with N2 or N3
      positive lymph nodes underwent neck dissection after the treatment. RESULTS: The
      mean age was 56.6 years (range, 34-75 years). The overall response rate to
      induction chemotherapy was 71.1%, with a 17.8% complete response rate and 53.3%
      partial response rate. With a median follow-up of 13.7 months, 23 (51.1%) of all
      patients and 63.3% of surviving patients have had a preservation of the larynx or
      hypopharynx and remain disease free. The most common toxicities were nausea and
      vomiting and mucositis. CONCLUSION: Organ preservation, with multimodality
      treatment, may be achievable in some of the patients with resectable, advanced
      larynx or hypopharynx cancers without apparent compromise of survival.

PMID- 15515159
TI  - Expression and significance of cancer testis antigens in primary mucosal melanoma
      of the head and neck.
AB  - BACKGROUND: Cancer testis antigens (CTAs) are T-cell-defined tumor-associated
      antigens encoded by the genes and gene families such as MAGE, NY-ESO-1, and
      others. Their expression in a wide variety of malignant neoplasms but absence in
      all normal adult tissue except testicular germ cells makes them attractive
      targets for immunotherapy of cancer. Primary mucosal melanomas of the head and
      neck (HNMM) are rare aggressive malignant tumors that are usually difficult to
      treat. CTAs may provide useful targets for therapy; however, their expression in
      HNMM is not known. METHODS: We analyzed 40 initial, 15 recurrent, and 15
      metastatic HNMM to nonmucosal locations from 64 patients (oral, n = 30;
      sinonasal, n = 34). Immunohistochemistry was performed on archival tissue with
      monoclonal antibodies 57B, CT7-33, and ES121 to the following CTAs: MAGE-A4, CT7
      (MAGE-C1), and NY-ESO-1, respectively. RESULTS: CT7, MAGE-A4, and NY-ESO-1
      expression was seen in 73%, 61%, and 24% of tumors, respectively, with 81% of the
      tumors expressing at least one of the CTAs. CT7 and MAGE-A4 were significantly
      more frequently expressed in tumors composed of epithelioid cells than spindle
      cells (p = .05). CTA expression did not correlate with disease progression,
      overall survival, and disease-specific survival. CONCLUSIONS: CT7, MAGEA4, and NY
      ESO-1 are frequently expressed in HNMM and may be potential targets for CTA-based
      immunotherapy. The expression does not seem to have prognostic significance.

PMID- 15515160
TI  - Fluorescence-based sensing system for copper using genetically engineered living
      yeast cells.
AB  - A whole cell-based optical sensing system for copper was developed based on
      Saccharomyces cerevisiae cells harboring plasmid pYEX-GFPuv. The basis of this
      system was the ability of the transcriptional activator protein Ace1 present in
      S. cerevisiae to control the expression of the reporter protein, GFPuv. When
      copper ions are present in the sample, the Ace1 protein activates the cup1
      promoter located upstream from the gfpuv gene in plasmid pYEX-GFPuv, thus
      inducing the production of GFPuv. The concentration of copper ions in the sample
      can then be related to the GFPuv expressed in the yeast. The amount of GFPuv
      produced in the system was determined by monitoring the fluorescence emitted at
      507 nm after excitation at 397 nm. This system can detect copper at
      concentrations as low as 5 x 10(-7) M, and is selective for copper over a variety
      of metal ions, with the exception of silver. The applicability of this sensing
      system to different analytical platforms and in real samples is demonstrated.

PMID- 15515161
TI  - Recovery in the fetal pancreatic islet following fetal administration of
      streptozotocin in the rat in vivo and in vitro.
AB  - In our previous study, after direct administration of streptozotocin (STZ; 400
      microg/g) to fetuses on day 19 of gestation, the B-cell volume in fetal
      pancreatic islets showed a marked decrease, but gradually recovered with electron
      microscopic confirmation of B-cell regeneration. However, STZ at this dose often
      caused fetal death. In this study, therefore, we determined whether B-cells are
      newly generated after treatment with STZ at a smaller dose in vivo and in vitro.
      For in vivo experiment, fetuses were administered STZ at 40 microg/g on day 19 of
      gestation. The B-cell volume in pancreatic islets decreased markedly 3 hr after
      the administration of STZ, but it began to increase after 6 hr. The fetal plasma
      insulin concentration decreased from 6 to 12 hr after the administration, but
      recovered after 48 hr. The cell division index in fetal pancreatic islets of the
      STZ-treated group began to be significantly larger after 6 hr. For in vitro
      experiment, fetal pancreases on day 18 of gestation were pretreated with 10 mM
      STZ for 6 hr and cultured for 98 hr. B-cells were completely destroyed with STZ
      treatment; however, as these pancreases were cultured in a medium free of STZ, B
      cells began to appear and insulin secretion was detected after 48 hr. After 72
      hr, the cell division index was significantly greater. These results suggest that
      the fetal pancreas treated with STZ has the ability to regenerate B-cells both in
      vivo and in vitro.

PMID- 15515162
TI  - Differential expression of estrogen receptors (ERalpha/ERbeta) in testis of
      mature and immature pigs.
AB  - High affinity estrogen receptors (ERs) mediate estrogen action in male
      reproductive tissues. The objective of the present study was the
      immunolocalization of estrogen receptor alpha and estrogen receptor beta in
      immature and mature testes of pig, a species in which the role of estrogens on
      gonadal function is scarcely known. Testes from 3 and 18 month-old pigs were
      investigated. Immunohistochemistry was performed on paraffin embedded-tissues
      using both mouse anti-human monoclonal IgG ERalpha and IgG ERbeta 1 isoform.
      Western blot analysis demonstrated antibody specificity. ERalpha staining was not
      observed in immature testes, but it was detected in spermatogonia, spermatocytes
      and in the most Leydig cells of mature testes. ERbeta immunoreactivity was
      observed in spermatogonia and Leydig cells of immature gonads, while it was
      clearly detected in spermatogonia and in spermatocytes of adult pig testes. The
      differential ERalpha/ERbeta expression in germ and somatic cells of the gonads
      suggest a role of estrogens in function and in development of pig testis.

PMID- 15515163
TI  - Use of the fertilized hen's egg in the evaluation of embryotoxicity of dental
      alloys.
AB  - In this study, embryotoxic effects of five commercially available dental alloys
      were investigated by using fertilized hens' eggs. One sample of each alloy was
      conditioned in one of the conditioning media, physiological saline (PS), 0.1 M
      phosphate-buffered saline (PBS, pH 7.4), and 0.1 M protein (3% bovine serum
      albumin, BSA) containing PBS (pH 6.8), respectively. The test solutions were
      injected into the fertilized hen's eggs via air sac at the beginning of the
      incubation. Various concentrations of a highly embryotoxic substance, AFB1, was
      also used as positive control test material. Mortality of the AFB1 treatment
      groups increased with increasing concentrations of AFB1 and the mortality values
      were significantly (p < 0.05) higher than those of the controls and eluent
      injected groups. The eluents of five commercially available dental alloys tested
      in the study did not have significant embryotoxic effects. Cu- and Pd-containing
      alloys displayed relatively high but statistically insignificant embryotoxic
      effects. Chick embryo might be used in determination of the embryotoxic effects
      of the dental alloys with its several advantages. Nevertheless, the test should
      be further standardized and new methods such as micronucleus test showing
      possible genotoxic effects of the materials should be used.

PMID- 15515164
TI  - Increased rate of chondrocyte aggregation in a wavy-walled bioreactor.
AB  - A novel wavy-walled bioreactor designed to enhance mixing at controlled shear
      stress levels was used to culture chondrocytes in suspension. Chondrocyte
      aggregation in suspensions mixed at 30, 50, and 80 rpm was characterized in the
      wavy-walled bioreactor and compared with that in conventional smooth-walled and
      baffled-walled spinner flask bioreactors. Aggregation was characterized in terms
      of the percentage of cells that aggregated over time, and aggregate size changes
      over time. The kinetics of chondrocyte aggregation observed in the bioreactors
      was composed of two phases: early aggregation between 0 and 2 h of culture, and
      late aggregation between 3 and 24 h of culture. At 50 rpm, the kinetics of early
      aggregation in the wavy-walled bioreactor was approximately 25% and 65% faster,
      respectively, than those in the smooth-walled and baffled-walled spinner flask
      bioreactors. During the late aggregation phase, the kinetics of aggregation in
      the wavy-walled bioreactor were approximately 45% and 65% faster, respectively,
      than in the smooth-walled and baffled-walled spinner flasks. The observed
      improved kinetics of chondrocyte aggregation was obtained at no cost to the cell
      survival rate. Results of computerized image analysis suggest that chondrocyte
      aggregation occurred initially by the formation of new aggregates via cell-cell
      interactions and later by the joining of small aggregates into larger cell
      clumps. Aggregates appeared to grow for only a couple of hours in culture before
      reaching a steady size, possibly determined by limitations imposed by the
      hydrodynamic environment. These results suggest that the novel geometry of the
      wavy-walled bioreactor generates a hydrodynamic environment distinct from those
      traditionally used to culture engineered cartilage. Such differences may be
      useful in studies aimed at distinguishing the effects of the hydrodynamic
      environment on tissue-engineered cartilage. Characterizing the wavy-walled
      bioreactor's hydrodynamic environment and its effects on cartilage cell/tissue
      culture can help establish direct relationships between hydrodynamic forces and
      engineered tissue properties.

PMID- 15515165
TI  - Theoretical and experimental analysis of analyte transport in a fiber-optic,
      protein C immuno-biosensor.
AB  - Protein C (PC) is an important anticoagulant in human blood plasma, and early
      diagnosis of PC deficiency is critical for preventing dangerous thromboembolic
      complications. A fiber-optic PC immuno-biosensor has been under development in
      our research group for real-time PC-deficiency diagnosis. The sensor has
      demonstrated a good sensitivity and specificity for quantifying PC in buffered
      solutions. However, for plasma samples, with a limited sample reaction time, the
      sensor produced only 30% of the signal intensity of PC in buffer. The high plasma
      viscosity (1.9 cP) was speculated as the major reason for signal intensity
      reduction. In this investigation, the sensing performance of the fiber-optic PC
      biosensor is systematically characterized in terms of physical and chemical
      properties of the sample media. Theoretical and experimental analyses indicate
      that the reduced diffusion rate of PC molecules in viscous samples caused the
      sensing system to be more mass-transfer-limited. Convective flow of
      sample/reagent solutions during immunoreactions can increase the rate of the
      analyte mass transport from the bulk solution to the sensor surface, with
      reaction kinetics changing from mass-transfer-limited to reaction-limited as flow
      velocity increases. It was shown that PC sensor performance was significantly
      improved for plasma samples with convection. The effect of the flow velocity and
      incubation times for samples and reagents on the sensor performance was also
      systematically analyzed to optimize the assay protocol for PC sensing. Currently,
      a 6-cm-long immuno-biosensor is capable of quantifying PC in plasma (1 mL) in the
      heterozygous PC deficiency range (0.5 to 2.5 microg/mL) within 5 minutes, at an
      average signal-to-noise ratio of 50.

PMID- 15515166
TI  - Murine leukemia virus clearance by flocculation and microfiltration.
AB  - Clearance of murine leukemia virus from CHO cell suspensions by flocculation and
      microfiltration was investigated. Murine leukemia virus is a retrovirus that is
      recommended by the U.S. Food and Drug Administration for validating clearance of
      retrovirus-like particles. Due to biosafety considerations, an amphotropic murine
      leukemia virus vector (A-MLV) that is incapable of self-replication was used.
      Further, A-MLV is incapable of infecting CHO cells, thus ensuring that infection
      of the CHO cells in the feed did not result in a reduced virus titer in the
      permeate. The virus vector contains the gene for the enhanced green fluorescent
      protein (EGFP) to facilitate assaying for infectious virus particles. The virus
      particles are 80-130 nm in size. The feed streams were flocculated using a
      cationic polyelectrolyte. Microfiltration was conducted using 0.1 and 0.65 microm
      pore size hollow fiber membranes. The level of virus clearance in the permeate
      was determined. For the 0.1 microm pore size membranes a 1,000-fold reduction in
      the virus titer in the permeate was observed for feed streams consisting of A
      MLV, A-MLV plus flocculant, A-MLV plus CHO cells, and A-MLV plus flocculant and
      CHO cells. While the flocculant had little effect on the level of virus clearance
      in the permeate for 0.1 microm pore size membranes, it did lead to higher
      permeate fluxes for the CHO cell feed streams. Virus clearance experiments
      conducted with 0.65 microm pore size membranes indicate little clearance of A-MLV
      from the permeate in the absence of flocculant. However, in the presence of
      flocculant the level of virus clearance in the permeate was similar to that
      observed for 0.1 microm pore size membranes. The results obtained here indicate
      that significant clearance of A-MLV is possible during tangential flow
      microfiltration. Addition of a flocculant is essential if the membrane pore size
      is greater than the diameter of the virus particles. Flocculation of the feed
      stream leads to an increase in the permeate flux.

PMID- 15515167
TI  - Kinetic analysis of RSK2 and Elk-1 interaction on the serum response element and
      implications for cellular engineering.
AB  - Immediate early gene activation upon mitogenic activation occurs through the
      serum response element (SRE), which makes the delineation of the upstream
      pathways a powerful means to engineer cellular responses. The malfunctioning of
      this system leads to a variety of disorders, ranging from neurological disorders
      such as Coffin-Lowry syndrome (RSK2 mutations) to cancer (c-fos mutations). We
      therefore investigated the SRE activation mechanism in a typical mammalian cell.
      Mitogenic signaling uses the mitogen-activated protein kinase (MAPK) module
      through increased binding of the ternary complex factor (TCF), such as Elk-1, to
      the promoter DNA (the SRE element) and subsequent transcriptional activation, as
      well as through activation of a histone kinase, such as the MAPK-activated
      protein kinase (MAPKAP-K) ribosomal S6 kinase (RSK2). This computational model
      uses the biochemical simulation environment GEPASI 3.30 to investigate three
      major models of interaction for Elk-1 and RSK2, and to study the effect of
      histone acetyl transferase (HAT) recruitment in each of these models on the local
      chromatin modifications in the presence and absence of MAPK activation. We show
      that the quickest response on the chromatin can be achieved in the presence of a
      preformed complex of RSK2, Elk-1 and HAT, with HAT being activated upon
      dissociation from the complex upon activation of the MAPK cascade. This study
      presents critical components in the pathway that can be targeted for engineering
      of specific inhibitors or activators of the system.

PMID- 15515168
TI  - Engineering Chinese hamster ovary cells to maximize effector function of produced
      antibodies using FUT8 siRNA.
AB  - We explored the possibility of converting established antibody-producing cells to
      cells producing high antibody-dependent cellular cytotoxicity (ADCC) antibodies.
      The conversion was made by constitutive expression of small interfering RNA
      (siRNA) against alpha1,6 fucosyltransferase (FUT8). We found two effective
      siRNAs, which reduce FUT8 mRNA expression to 20% when introduced into Chinese
      hamster ovary (CHO)/DG44 cells. Selection for Lens culinaris agglutinin (LCA)
      resistant clones after introduction of the FUT8 siRNA expression plasmids yields
      clones producing highly defucosylated (approximately 60%) antibody with over 100
      fold higher ADCC compared to antibody produced by the parental cells
      (approximately 10% defucosylated). Moreover, the selected clones remain stable,
      producing defucosylated antibody even in serum-free fed-batch culture. Our
      results demonstrate that constitutive FUT8 siRNA expression can control the
      oligosaccharide structure of recombinant antibody produced by CHO cells to yield
      antibodies with dramatically enhanced ADCC.

PMID- 15515169
TI  - Fluorescence and CD spectroscopic analysis of the alpha-chymotrypsin
      stabilization by the ionic liquid, 1-ethyl-3-methylimidazolium
      bis[(trifluoromethyl)sulfonyl]amide.
AB  - The stability of alpha-chymotrypsin in the ionic liquid, 1-ethyl-3-methyl
      imidizolium bis[(trifluoromethyl)sulfonyl]amide ([emim][NTf2]), was studied at 30
      and 50 degrees C and compared with the stability in other liquid media, such as
      water, 3 M sorbitol, and 1-propanol. The kinetic analysis of the enzyme stability
      pointed to the clear denaturative effect of 1-propanol, while both 3M sorbitol
      and [emim][NTf2] displayed a strong stabilizing power. For the first time, it is
      shown that enzyme stabilization by ionic liquids seems to be related to the
      associated structural changes of the protein that can be observed by differential
      scanning calorimetry (DSC) and fluorescence and circular dichroism (CD). The
      [emim][NTf2] enhanced both the melting temperature and heat capacity of the
      enzyme compared to the other media assayed. The fluorescence spectra clearly
      showed the ability of [emim][NTf2] to compact the native structural conformation
      of alpha-chymotrypsin, preventing the usual thermal unfolding which occurs in
      other media. Changes in the secondary structure of this beta/beta protein, as
      quantified by the CD spectra, pointed to the great enhancement (up 40% with
      respect to that in water) of beta-strands in the presence of the ionic liquid,
      which reflects its stabilization power.

PMID- 15515172
TI  - Comparison of gene expression changes induced in mouse and human cells treated
      with direct-acting mutagens.
AB  - Exposure to DNA-damaging agents can elicit a variety of stress-related responses
      that may alter the gene expression of numerous biological pathways. We used
      Affymetrix microarrays to detect gene expression changes in mouse lymphoma
      (L5178Y) and human lymphoblastoid (TK6) cells in response to methyl
      methanesulfonate (MMS; a prototypical alkylating agent) and bleomycin (a
      prototypical oxidative mutagen). Cells were treated for 4 hr, and RNA was
      isolated either at the end of the treatment or after a 20-hr recovery period. Two
      concentrations of each agent were used based on cytotoxicity levels and Tk mutant
      frequencies. Our microarray data analysis indicated that MMS and bleomycin gene
      expression responses were considerably different in mouse cells versus human
      cells. The results also suggested that more comprehensive cellular responses to
      MMS and bleomycin occurred in TK6 cells than in L5178Y cells. In contrast to
      L5178Y cells, the response of TK6 cells to MMS and bleomycin was characterized by
      the induction of p53-dependent genes that are involved in DNA repair, cell cycle
      regulation, and apoptosis. It appears that the induction of DNA damage by MMS in
      human TK6 cells mediated cytotoxicity and led to decreased cell survival. This
      may explain the greater sensitivity of TK6 cells to cytotoxic effects of MMS
      compared to L5178Y cells. Bleomycin exerted comparable cytotoxic effects in the
      two cell lines. Overall, these studies were unable to identify distinctive gene
      expression changes that differentiated bleomycin from MMS in either TK6 cells or
      mouse lymphoma cells.

PMID- 15515173
TI  - Septal columns in rodent barrel cortex: functional circuits for modulating
      whisking behavior.
AB  - In rodents, each mystacial whisker is represented in the granular layer of
      primary somatosensory (SI) cortex by a compact cluster of cells known as a
      barrel, and barrels are separated from each other by domains that are called
      septa. Vertical columns of neurons aligned with each barrel act as a functional
      assembly to process information from a "principal" whisker, but a functional role
      has not been identified for vertical columns of neurons that are aligned with the
      septa. To determine whether these septal columns provide the main source of
      projections to primary motor (MI) cortex, we placed retrograde tracers in MI
      cortex and analyzed the location of the retrogradely labeled neurons with respect
      to the septal and barrel compartments of SI barrel cortex. In cases in which SI
      barrel cortex was sectioned tangentially, retrogradely labeled neurons in the
      extragranular layers of SI were plotted and superimposed onto reconstructions of
      the layer IV barrel field. In each of these cases, most labeled neurons were
      located above or below the septal regions of layer IV. When SI barrel cortex was
      sectioned coronally, we observed multiple columns of labeled SI neurons that were
      vertically aligned with the septal zones of layer IV. These results indicate that
      columns of neurons that are vertically aligned with the septa, or septal columns,
      are functionally linked by virtue of their projections to MI cortex. We
      hypothesize that these septal columns represent an interconnected and
      functionally distinct circuit that transmits information to MI and other brain
      regions involved in motor control.

PMID- 15515174
TI  - Chondrocyte terminal differentiation, apoptosis, and type X collagen expression
      are downregulated by parathyroid hormone.
AB  - Parathyroid hormone (PTH) regulates calcium and phosphate homeostasis through the
      endocrine system. Parathyroid hormone-related peptide (PTHrP) is a heterogeneous
      polypeptide with sequence homology to PTH in its first 13 amino acid residues.
      Both bind and activate a common receptor, the type 1 PTH/PTHrP receptor (PTH1R).
      Activation of this G-protein-coupled receptor by PTHrP has been shown to regulate
      chondrogenesis in a manner that attenuates chondrocyte hypertrophy. Here, we
      report the dose-response (10(-7) to 10(-15) M) effects of PTH on chondrogenesis
      using an avian sternal organ culture model. PTH increased cartilaginous tissue
      length and downregulated the deposition of type X collagen and its mRNA
      expression. In addition, PTH increased chondrocyte cell diameter in
      prehypertrophic and proliferative regions while decreasing chondrocyte apoptosis
      in the hypertrophic zone. In conclusion, these experiments demonstrate that PTH
      regulates cartilage growth, chondrocytic apoptosis, deposition of type X collagen
      protein, and expression of type X collagen mRNA. Type X collagen mRNA expression
      was downregulated by PTH in this organ culture model, but cell size, another
      marker for terminal differentiation, increased.

PMID- 15515175
TI  - Expression of the vesicular glutamate transporters during development indicates
      the widespread corelease of multiple neurotransmitters.
AB  - Three closely related proteins transport glutamate into synaptic vesicles for
      release by exocytosis. Complementary patterns of expression in glutamatergic
      terminals have been reported for VGLUT1 and VGLUT2. VGLUT3 shows expression by
      many cells not considered to be glutamatergic. Here we describe the changes in
      VGLUT expression that occur during development. VGLUT1 expression increases
      gradually after birth and eventually predominates over the other isoforms in
      telencephalic regions. Expressed at high levels shortly after birth, VGLUT2
      declines with age in multiple regions, in the cerebellum by 14-fold. In contrast,
      Coexpression of the two isoforms occurs transiently during development as well as
      permanently in a restricted subset of glutamatergic terminals in the adult.
      VGLUT3 is transiently expressed at high levels by select neuronal populations,
      including terminals in the cerebellar nuclei, scattered neurons in the cortex,
      and progenitor-like cells, implicating exocytotic glutamate release in
      morphogenesis and development. VGLUT3 also colocalizes extensively during
      development with the neuronal vesicular monoamine transporter VMAT2, with the
      vesicular acetylcholine transporter VAChT, and with the vesicular gamma
      aminobutyric acid transporter VGAT. Such coexpression occurs particularly at some
      specific developmental stages and is restricted to certain sets of cells. In
      skeletal muscle, VGLUT3 localizes to granular organelles in the axon terminal as
      well as in the muscle sarcoplasm. The results suggest novel mechanisms and roles
      for regulated transmitter release.

PMID- 15515176
TI  - Projection and local interneurons in the sixth abdominal ganglion of the sand
      crab Emerita analoga (Hippidae).
AB  - Hippid crabs are adapted for life in the surf zone of exposed sandy beaches, and
      their tailfan differs from the tailfans of other crustaceans with respect to
      morphology and motor control and in having nonspiking stretch receptors (NSR). To
      investigate how these crabs' mechanosensory systems are adapted to this turbulent
      environment, I used axonal back-filling and intracellular recording with dye
      filled microelectrodes to describe afferent projections from the telson and
      morphologies and physiological responses of intersegmental and local neurons in
      abdominal ganglion 6 (A6) in Emerita analoga, then compared them with
      descriptions of corresponding neurons in A6 of crayfish. The density of afferent
      terminals and the proportion of projection neuron somata is lower in anterior A6
      of E. analoga than in crayfish, perhaps correlated with a reduction in
      hydrodynamic setae. Many interneurons responded to afferent nerve stimulation and
      displayed activity correlated with levels of A6 motor output. NSR stretch
      depolarizes unilateral local neurons and terminals of axons entering A6 from the
      connective and hyperpolarizes bilateral local and projection neurons. The timing
      and duration of this inhibition would suppress mechanosensory input from the
      telson during uropod beating (homologue of crayfish's nongiant tail-flipping).
      Suppression of reafference during uropod beating may have been pivotal for
      evolution of hippids' ability to move rapidly across the water-sand interface in
      the slosh zone of sandy beaches. Homologies between A6 neurons in E. analoga and
      crayfish, suggested by morphological and physiological similarities, indicate
      that the NSRs connect to a neuronal network regulating exteroceptive input that
      was inherited from their tail-flipping ancestors.

PMID- 15515178
TI  - Synaptic structural abnormalities in the Ts65Dn mouse model of Down Syndrome.
AB  - The Ts65Dn mouse is a genetic model for Down syndrome. Although this mouse shows
      abnormalities in cognitive function that implicate hippocampus as well as marked
      deficits in hippocampal long-term potentiation, the structure of the hippocampus
      has been little studied. We characterized synaptic structure in Ts65Dn and
      control (2N) mice, studying the hippocampus (fascia dentata, CA1) as well as the
      motor and somatosensory cortex, entorhinal cortex, and medial septum. Confocal
      microscopy was used to examine immunostained presynaptic boutons and to detail
      the structure of dendrites after Lucifer yellow microinjection. Both presynaptic
      and postsynaptic elements were significantly enlarged in Ts65Dn in all regions
      examined. The changes were detected at the youngest age examined (postnatal day
      21) and in adults. In studies detailing the changes in fascia dentata and motor
      cortex, the enlargement of spines affected the entire population, resulting in
      the presence of spines whose volume was greatly increased. Electron microscopy
      confirmed that boutons and spines were enlarged and demonstrated abnormalities in
      the internal membranes of both. In addition, spine density was decreased on the
      dendrites of dentate granule cells, and there was reorganization of inhibitory
      inputs, with a relative decrease in inputs to dendrite shafts and an increase in
      inputs to the necks of spines. Taken together, the findings document widespread
      abnormalities of synaptic structure that recapitulate important features seen in
      Down syndrome. They establish the Ts65Dn mouse as a model for abnormal synapse
      structure and function in Down syndrome and point to the importance of studies to
      elucidate the mechanisms responsible for synapse enlargement.

PMID- 15515179
TI  - Influence of porcine liver esterase on the color of dental resin composites by
      CIEDE2000 system.
AB  - The objectives of this study were to evaluate the changes in color and color
      coordinates of dental resin composites after immersion in porcine liver esterase
      (PLE, 400 mU/mL; a substitute for salivary hydrolase) with CIEDE2000 color
      system, and to compare those with CIELAB color system. Color of resin composites
      was measured after immersion in PBS (phosphate buffered saline; control) or PLE
      up to nine weeks. Color difference (delta E00) and changes in lightness (L'), red
      green parameter (a'), yellow-blue parameter (b'), and chroma (C') with CIEDE2000
      system were compared. Correlation in the changes of color with CIEDE2000 and
      CIELAB systems was determined. Delta E00 values after a 9-week immersion in PLE
      were 0.7-2.8, which were not higher than those in PBS except for a few cases.
      Changes in b' and C' values after a 9-week immersion in PLE were generally lower
      than those in PBS, and were in the range of -4.0 to -0.1 and -4.0 to -0.1,
      respectively. Therefore, the influence of porcine liver esterase on the changes
      of color and color coordinates was negligible with CIEDE2000 color system. There
      was a significant correlation between color differences (delta E00 vs deltaE*ab)
      with CIEDE2000 and CIELAB systems [correlation coefficient (r) = 0.95, p < 0.01].

PMID- 15515180
TI  - Thyroxine revisited.
AB  - The crystal structure of the common therapeutic agent, the pentahydrated sodium
      salt of L-thyroxine hormone (3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]
      L-alanine), has been determined and discussed in relation to the drug's
      stability. The stoichiometry and absolute configuration (-)-C(8)S-[C15H10I4NO4]
      .Na+.5H2O have been confirmed. The crystals are built of a three-dimensional
      supramolecular network with two symmetry-independent L-thyroxine anions, in two
      distinct conformations not previously reported, linked by strong NH-O hydrogen
      bonds into dimers. Two independent sodium cations are fivefold and sixfold
      coordinated. The cations and two independent water molecules not involved in
      coordinating the Na cations form sheets along the crystallographic (001) planes.
      The presence of differently coordinated cations and non-coordinating water
      molecules may be responsible for water transport and loss, for decay of the
      crystals, and subsequent low stability of the drug. Only a conglomerate could be
      obtained when racemic sodium thyroxine was crystallized from ethanol and methanol
      solutions by evaporation, which explains the equal penta-hydration of the sodium
      salts of enantiomorphic and racemic thyroxine, and the fact that there are no
      apparent differences in their stability.

PMID- 15515182
TI  - A genomic perspective of protein kinases in Plasmodium falciparum.
AB  - Protein kinases are central to regulation of cellular signaling in the
      eukaryotes. Well-conserved and lineage-specific protein kinases have previously
      been identified from various completely sequenced genomes of eukaryotes. The
      current work describes a genome-wide analysis for protein kinases encoded in the
      Plasmodium falciparum genome. Using a few different profile matching methods, we
      have identified 99 protein kinases or related proteins in the parasite genome. We
      have classified these kinases into subfamilies and analyzed them in the context
      of noncatalytic domains that occur in these catalytic kinase domain-containing
      proteins. Compared to most eukaryotic protein kinases, these sequences vary
      significantly in terms of their lengths, inserts in catalytic domains, and co
      occurring domains. Catalytic and noncatalytic domains contain long stretches of
      repeats of positively charged and other polar amino acids. Various components of
      the cell cycle, including 4 cyclin-dependent kinase (CDK) homologues, 2 cyclins,
      1 CDK regulatory subunit, and 1 kinase-associated phosphatase, are identified.
      Identification of putative mitogen-activated protein (MAP) Kinase and MAP Kinase
      Kinase of P. falciparum suggests a new paradigm in the highly conserved signaling
      pathway of eukaryotes. The calcium-dependent kinase family, well represented in
      P. falciparum, shows varying domain combinations with EF-hands and pleckstrin
      homology domains. The analysis reveals a new subfamily of protein kinases having
      limited sequence similarity with previously known subfamilies. A new
      transmembrane kinase with 6 membrane-spanning regions is identified. Putative
      apicoplast targeting sequences have been detected in some of these protein
      kinases, suggesting their export to the apicoplast.

PMID- 15515181
TI  - The impact of protein flexibility on protein-protein docking.
AB  - Accounting for protein flexibility in protein-protein docking algorithms is
      challenging, and most algorithms therefore treat proteins as rigid bodies or
      permit side-chain motion only. While the consequences are obvious when there are
      large conformational changes upon binding, the situation is less clear for the
      modest conformational changes that occur upon formation of most protein-protein
      complexes. We have therefore studied the impact of local protein flexibility on
      protein-protein association by means of rigid body and torsion angle dynamics
      simulation. The binding of barnase and barstar was chosen as a model system for
      this study, because the complexation of these 2 proteins is well-characterized
      experimentally, and the conformational changes accompanying binding are modest.
      On the side-chain level, we show that the orientation of particular residues at
      the interface (so-called hotspot residues) have a crucial influence on the way
      contacts are established during docking from short protein separations of
      approximately 5 A. However, side-chain torsion angle dynamics simulations did not
      result in satisfactory docking of the proteins when using the unbound protein
      structures. This can be explained by our observations that, on the backbone
      level, even small (2 A) local loop deformations affect the dynamics of contact
      formation upon docking. Complementary shape-based docking calculations confirm
      this result, which indicates that both side-chain and backbone levels of
      flexibility influence short-range protein-protein association and should be
      treated simultaneously for atomic-detail computational docking of proteins.

PMID- 15515183
TI  - Both helical propensity and side-chain hydrophobicity at a partially exposed site
      in alpha-helix contribute to the thermodynamic stability of ubiquitin.
AB  - Improving helical propensity of residues was proposed as one of the approaches to
      increase protein stability. Here the contribution of the helix propensity and
      hydrophobicity of residues at partially buried positions of alpha-helix to the
      stability of a model protein-ubiquitin- is explored. Thermodynamic stabilities of
      13 ubiquitin variants with substitutions at a partially buried helical residue
      were measured by differential scanning calorimetry. It was found that the dynamic
      range of stabilities for different amino acid residues at this partially buried
      position is 3 times larger than that expected based on helical propensity alone.
      Correlation analysis shows that both helical propensity and hydrophobicity are
      important in defining the relative stabilities of the studied ubiquitin variants.
      These results provide experimental evidence that partially buried positions are
      potentially useful sites for engineering proteins with enhanced thermostability.

PMID- 15515185
TI  - Telemedicine in the USA with focus on clinical applications and issues.
AB  - Telemedicine usually refers to the use of information-based technologies, such
      as, computer and communications systems, to provide healthcare across geographic
      distances. Although telemedicine has the potential to improve healthcare, the
      number of clinical applications is still small and constrained by custom,
      regulatory, reimbursement and technical issues. In this review paper, a short
      historical review of telemedicine is provided, followed by an overview of
      clinical telemedicine applications, including cardiology, dermatology, emergency
      medicine and trauma care, homecare, pathology, psychiatry, radiology and surgery.
      Current telemedicine issues in clinics and technological problems to be decided,
      improved, and challenged, are reviewed. This is followed by conclusions.

PMID- 15515184
TI  - DARPP-32-like immunoreactivity in AII amacrine cells of rat retina.
AB  - Previous studies demonstrated that the dopamine- and adenosine 3',5'
      monophosphate-regulated phosphatase inhibitor known as "DARPP-32" is present in
      rat, cat, monkey, and human retinas. We have followed up these studies by asking
      what specific cell subtypes contain DARPP-32. Using a polyclonal antibody
      directed against a peptide sequence of human DARPP-32, we immunostained adult rat
      retinas that were either transretinally sectioned or flat mounted and found DARPP
      32-like immunoreactivity in some cells of the amacrine cell layer across the
      entire retinal surface. We report here, based on the shape and spatial
      distribution of these cells, their staining by an anti-parvalbumin antibody, and
      their juxtaposition with processes containing tyrosine hydroxylase, that DARPP-32
      like immunoreactivity is present in AII amacrine cells of rat retina. These
      results suggest that the response of AII amacrine cells to dopamine is not
      mediated as simply as previously supposed.

PMID- 15515186
TI  - Antioxidant effects of sulfur-containing amino acids.
AB  - Sulfur is an essential element for the entire biological kingdom because of its
      incorporation into amino acids, proteins and other biomolecules. Sulfur atoms are
      also important in the iron-containing flavoenzymes. Unlike humans, plants can use
      inorganic sulfur to synthesize sulfur-containing amino acids. Therefore, plants
      are an important source of sulfur for humans. Sulfur-containing compounds are
      found in all body cells and are indispensable for life. Some of sulfur-containing
      antioxidant compounds are, cysteine, methionine, taurine, glutathione, lipoic
      acid, mercaptopropionylglycine, N-acetylcysteine, and the three major
      organosulfur compounds of garlic oil, diallylsulfide, diallyldisulfide and
      diallyltrisulfide. In a comparison of the structure-function relationship among
      these sulfur-containing antioxidant compounds, dihydrolipoic acid (the reduced
      form of LA) is the most effective antioxidant. Dihydrolipoic acid contains two
      sulfhydryl groups and can undergo further oxidation reaction to form lipoic acid.
      The antioxidative activities of sulfur-containing compounds follow a general
      trend, the more highly reduced forms are stronger antioxidants and the number of
      sulfur atoms determine, at least in part, their modulatory activites on the
      glutathione related antioxidant enzymes. In this article, the antioxidant effects
      and the antioxidative activities, of sulfur-containing amino acids, are reviewed.
      In addition, the general antioxidant effects and the structure-function
      relationship of some sulfur-containing compounds are also reviewed.

PMID- 15515187
TI  - Comparison of continuous epidural and intravenous analgesia for postoperative
      pain control in pediatric lower extremity surgery.
AB  - In recent years epidural anesthesia and analgesia techniques were used in
      pediatric surgery owing to the development of pediatric epidural catheter
      needles. And the need of postoperative pain control in pediatric patients is also
      increasing. We compared combined general-epidural anesthesia and analgesia
      technique with intravenous fentanyl analgesia after general anesthesia for
      postoperative analgesic effect and complications in these pediatric patients. We
      randomly allocated 91 pediatric patients undergoing lower extremities surgery
      into epidural lidocaine group (n=61) and IV fentanyl group (n=30). During the
      operation, end-tidal sevoflurane concentration (ET(sev)) was controlled to
      maintain the blood pressure and heart rate within 10% of preoperative value. At
      the postoperative period, Parent Visual Analog Scale (PVAS), Objective Pain Score
      (OPS) and the incidence of nausea/ vomiting were checked immediately, 6 hours and
      24 hours after the patient's arrival at general ward. ET(sev) was significantly
      low in epidural lidocaine group (p < 0.05). Compare to IV fentanyl group,
      epidural lidocaine group had significantly lower OPSs at 6 hours after arrival.
      Epidural lidocaine group had significantly lower PVASs immediately, 6 hrs and 24
      hours after arrival. There was no significant difference in the incidence of
      postoperative nausea and vomiting. A combined general-epidural anesthesia
      technique significantly reduces intraoperative end-tidal sevoflurane
      concentration compared to general anesthesia alone. And continuous patient
      controlled epidural analgesia reduces postoperative pain scores significantly
      more than continuous patient-controlled IV fentanyl analgesia without any serious
      complications in pediatric lower extremity surgery.

PMID- 15515188
TI  - Correlation between cognitive capacity screening examination and cognitive evoked
      potential in alcohol-dependent patients.
AB  - The aim of this study was to verify the significance of cognitive evoked
      potentials and the correlation between the auditory event-related potential and
      the Cognitive Capacity Screening Examination (CCSE) in alcohol dependent
      patients. The P300 studies using an auditory paradigm were performed on 25
      alcohol dependent patients, and then the results were compared with score of the
      CCSE. 1) The latencies of the P300 were significantly prolonged in the patient
      group compared with the control group, and the scores of CCSE were significantly
      reduced in the patient group compared with the control group (p < 0.05). 2) There
      were significant negative correlation between P300 latency and scores of the CCSE
      (p < 0.05, r= -0.774). 3) There were no significant correlation between P300
      latency and the total amount of ethanol ingestion (p > 0.05). 4) There was
      significant reliability in P300 latency study (alpha=0.9771). These findings
      suggest that the latency of P300 may be useful as a clinical electrodiagnostic
      measurement that can objectively reflect cognitive dysfunction in alcohol
      dependent patients, and it can be used as a quantitative analysis of cognitive
      dysfunction even for early asymptomatic alcohol dependent patients.

PMID- 15515189
TI  - Food sensitization in infants and young children with atopic dermatitis.
AB  - Atopic dermatitis (AD) is a chronic, relapsing, inflammatory skin disease.
      Children with AD tend to have a higher prevalence of food allergies. This study
      investigated the clinical significance of food sensitization in AD patients. A
      total of 266 AD patients participated in this study. The prevalence of food
      sensitization and clinically relevant sensitization were compared in the subjects
      according to their age and AD severity. Sera from all patients were analyzed for
      food-specific IgE levels using the Pharmacia CAP System FEIA. The serum specific
      IgE levels for egg, milk, peanut and soybean were measured. Patients were
      regarded as sensitized to the food if their food-specific IgE levels were above
      0.35 kUA/L. Also the food-specific IgE levels, the so-called diagnostic decision
      point, which is recommended as the clinically relevant level, for clinical food
      allergy, as suggested by Sampson et al, was used as an alternative method. From
      the measurement of food-specific IgE antibodies of the four foods, egg was the
      most highly sensitized and the main causative allergenic food in children with
      AD. The positive rates of specific IgE to the four major food allergens, and the
      prevalences of clinically relevant food sensitization, were higher for all foods
      tested in the group less than 1 year of age, and were significantly higher in
      moderate to severe AD compared to mild AD in infants and young children. In
      summary, presence of food specific IgE is prevalent in infants and young children
      with AD, and clinically relevant food sensitization is important in Korean
      infants and children with moderate to severe AD.

PMID- 15515190
TI  - Specially programmed respiratory muscle training for singers by using respiratory
      muscle training device (Ultrabreathe).
AB  - Respiratory muscle training is one of the major methods for enhancing the vocal
      function. Singers who must use their voice most frequently are well aware of the
      importance of respiration. However, most of them do not know precisely how to
      exercise their abdominal respiration. Using a respiratory training device,
      singers are expected to gain more efficiency in their vocal enhancement. The aim
      of the study was to examine the pulmonary function, the maximum inspiratory
      pressure (MIP) and the maximum expiratory pressure (MEP), and the maximum
      phonation time (MPT) in five female voice-majors students after undergoing
      specially programmed respiratory muscle training for 2 months. All the voice
      majors had an average of 4.8 years of formal classical voice training. A
      respiratory muscle training device (Ultrabreathe), Tangent health Care Inc.,
      England) was used to train the respiratory muscle. None of the pulmonary function
      test variables had changed after respiratory muscle training. However, the MIP,
      MEP, and MPT were significantly increased higher after the respiratory muscle
      training. This suggests that the specially programmed respiratory muscle training
      can improve the respiratory muscle strength and vocal function without increasing
      the pulmonary function.

PMID- 15515191
TI  - Mutations of the BRAF gene in papillary thyroid carcinoma in a Korean population.
AB  - The B-type Raf kinase (BRAF) protein is a serine/threonine kinase that has an
      important role in cellular proliferation, differentiation, and programmed cell
      death. The BRAF gene has been recently found to be mutated in human carcinomas,
      predominantly in malignant melanoma. The aim of this study was to investigate the
      frequency of the BRAF mutation in papillary thyroid carcinoma (PTC) of Koreans
      through direct DNA sequencing of the polymerase chain reaction (PCR)- amplified
      exon 15 with clinicopathological features. Seventy paraffin-embedded conventional
      papillary carcinomas in the thyroid gland were evaluated. The BRAF missense
      mutation at V599E was found in 58 of 70 PTCs (83%). The frequency of our series
      was much higher than the frequencies of other PTC series (36 - 69%). The
      frequency of nodal metastasis was also significantly higher in the BRAF mutation
      group (p= 0.048). These results suggest that the BRAF mutation is involved in the
      carcinogenesis in most conventional PTCs, especially those occurring in Koreans,
      and this is a potentially valuable marker for the evaluation of prognosis of
      patients with PTC. These findings support the specific inhibitors of BRAF being
      promising targets for the disease outcome.

PMID- 15515193
TI  - Multiple imputation technique applied to appropriateness ratings in cataract
      surgery.
AB  - Missing data such as appropriateness ratings in clinical research are a common
      problem and this often yields a biased result. This paper aims to introduce the
      multiple imputation method to handle missing data in clinical research and to
      suggest that the multiple imputation technique can give more accurate estimates
      than those of a complete-case analysis. The idea of multiple imputation is that
      each missing value is replaced with more than one plausible value. The
      appropriateness method was developed as a pragmatic solution to problem of trying
      to assess "appropriate" surgical and medical procedures for patients. Cataract
      surgery was selected as one of four procedures that were evaluated as a part of
      the Clinical Appropriateness Initiative. We created mild to high missing rates of
      10%, 30% and 50% and compared the performance of logistic regression in cataract
      surgery. We treated the coefficients in the original data as true parameters and
      compared them with the other results. In the mild missing rate (10%), the
      deviation from the true coefficients was quite small and ignorable. After
      removing the missing data, the complete-case analysis did not reveal any serious
      bias. However, as the missing rate increased, the bias was not ignorable and it
      distorted the result. This simulation study suggests that a multiple imputation
      technique can give more accurate estimates than those of a complete-case
      analysis, especially for moderate to high missing rates (30 - 50%). In addition,
      the multiple imputation technique yields better accuracy than a single imputation
      technique. Therefore, multiple imputation is useful and efficient for a situation
      in clinical research where there is large amounts of missing data.

PMID- 15515192
TI  - The effects of urokinase instillation therapy via percutaneous transthoracic
      catheter in loculated tuberculous pleural effusion: a randomized prospective
      study.
AB  - The purpose of this study was to propose that intrapleural urokinase (UK)
      instillation could reduce pleural thickening in the treatment of loculated
      tuberculous pleural effusion. Forty- three patients who were initially diagnosed
      as having loculated tuberculous pleural effusion were assigned at random to
      receive either the combined treatment of UK instillation including anti
      tuberculosis agents (UK group, 21 patients) or strictly the unaccompanied anti
      tuberculous agents (control group, 22 patients). The UK group received 100,000 IU
      of UK dissolved in 150 ml of normal saline daily, introduced into the pleural
      cavity via a pig-tail catheter. The control group was treated with anti
      tuberculous agents, excepting diagnostic thoracentesis. After the cessation of
      treatment, residual pleural thickening (RPT) was compared between the two groups.
      Clinical characteristics and pleural fluid biochemistry were also evaluated. The
      RPT (4.59 +/- 5.93 mm) of the UK group was significantly lower than that (18.6 +/
      26.37 mm) of the control group (p < 0.05). The interval of symptoms observed
      prior to treatment of patients with RPT > or = 10 mm (6.0 +/- 3.4 wks) was
      detected to be significantly longer than in those with RPT < 10 mm (2.1 +/- 1.2
      wks) in the control group (p < 0.05). However, there were no discernible
      differences were seen in the pleural fluid parameter in patients with RPT > or =
      10 mm, as compared to patients with RPT < 10 mm in the UK group. These results
      indicate that the treatment of loculated tuberculous pleural effusion with UK
      instillation via percutaneous transthoracic catheter can cause a successful
      reduction in pleural thickening.

PMID- 15515194
TI  - Association between job stress on heart rate variability and metabolic syndrome
      in shipyard male workers.
AB  - A growing body of literature has documented that job stress is associated with
      the development of cardiovascular disease. Nevertheless, the pathophysiological
      mechanism of this association remains unclear. The purpose of this study is to
      elucidate the relationship between job stress, heart rate variability, and
      metabolic syndrome. The study design was cross-sectional, and a total of 169
      industrial workers were recruited. A structured-questionnaire was used to assess
      the general characteristics and job characteristics (work demand, decision
      latitude). Heart rate variability (HRV) was recorded using SA-2000 (medi-core),
      and was assessed by time-domain and by frequency-domain analyses. Time domain
      analysis was performed using SDNN (Standard Deviation of normal to normal
      interval), and spectral analysis using low-frequency (LF), high-frequency (HF),
      and total frequency power. Metabolic syndrome was defined on the basis of risk
      factors being clustered when three or more of the following cardiovascular risk
      factors were included in the fifth quintile: glucose, systolic blood pressure,
      high-density lipoprotein cholesterol (bottom quintile), triglyceride, and waist
      hip ratio. The results showed that job characteristics were not associated with
      cardiovascular risk factors. Compared to the lower strain group (low
      strain+passive+active group), the high strain group had a less favorable
      cardiovascular risk profile with higher levels of blood pressure, glucose,
      homocysteine, and clotting factor, but the difference was not statistically
      significant. The SDNN of HRV was significantly lower in the high strain group
      than in the low strain group. The prevalence of metabolic syndrome in the lower
      strain group and high strain group was 13.2% and 23.8%, respectively. In the high
      strain group, the metabolic syndrome was significantly related to a decreased
      SDNN. However, we could not find a significant association in LF/HF ratio. This
      result suggests that decreased HRV found in the high-strain group are not a
      direct indicator of disease. However, it can induce cardiovascular abnormalities
      or dysfunctions related to the onset of heart disease among high risk groups.

PMID- 15515195
TI  - Treatment outcome of transcatheter arterial chemoinfusion according to anticancer
      agents and prognostic factors in patients with advanced hepatocellular carcinoma
      (TNM stage IVa).
AB  - Transcatheter arterial chemoinfusion (TACI) is the main treatment modality for
      advanced hepatocellular carcinoma (HCC). However, the therapeutic efficacy of
      TACI according to anti-cancer agents and prognostic factors for advanced HCC (TNM
      stage IVa) has not been previously clarified. A total of 127 patients with TNM
      stage IVa HCC were divided into intra-arterial Adriamycin (Group I) and intra
      arterial Cisplatin (Group II) infused groups, according to the anticancer agents
      that were used. We compared the therapeutic efficacy of TACI applied anticancer
      agents, and we also analyzed the prognostic factors which influenced the survival
      rates. Chi-square test, t- test, Cox's proportional hazard regression model, and
      Kaplan- Meier method were performed. The overall survival was significantly
      different (10.0 vs 5.7 months, respectively) and the results favored Group I. On
      univariate analysis, the significant prognostic factors included age, portal vein
      thrombosis (PVT), tumor size (diameter > 5 cm), type of tumor, the reduction rate
      (tumor size and alpha- fetoprotein) after 3 months of chemotherapy, serum albumin
      level, serum alkaline phosphatase level and total serum bilirubin levels at the
      time of diagnosis. After repeated chemotherapy, Group I showed better survival
      (14.0 vs 7.9 months). However, there was no statistical difference in the
      survival rate of the two groups for cases involving large tumors, PVT and diffuse
      type of HCC. Group I showed better survival than Group II. However, when the
      other prognostic factors were taken into consideration, there was no significant
      difference in the survival rate of the two groups, except for the cases with
      small or nodular HCC.

PMID- 15515196
TI  - Peritubular capillary C4d deposition in chronic allograft dysfunction.
AB  - Peritubular capillary (PTC) C4d staining represents a marker for acute humoral
      rejection, however, the impact of positive staining on chronic allograft
      dysfunction has received little attention. Ninety-three renal allograft biopsies
      from 93 patients were selected from a total of 174 renal allograft biopsies,
      which were obtained 6 months or more after transplantation (median: 89 months).
      Fresh frozen renal tissue was stained with monoclonal antibody against C4d.
      Sixteen of 93 biopsies showed C4d staining in PTC. C4d staining was positive in
      40% of acute rejection cases (n=15) and 21% of chronic rejection cases (n=24).
      When the samples were divided according to C4d positivity, the C4d (+) group had
      a higher proportion of acute rejection than the C4d (-) group. However, no
      significant difference was observed between the two groups in terms of the
      prevalence of chronic rejection. Degrees of histological injury including
      tubulitis, interstitial inflammation and interstitial fibrosis were not
      significantly different between C4d (+) and C4d (-) groups. However, the 2-year
      graft survival rate after biopsy was lower in the C4d (+) group than in the C4d (
      ) group (24.8% versus 59.0%, p=0.1255). C4d staining in PTC is associated with
      late acute rejection, but not with chronic rejection based on conventional
      morphologic criteria in patients with chronic allograft dysfunction.

PMID- 15515197
TI  - Clinical outcomes of tuberculosis in renal transplant recipients.
AB  - Tuberculosis (TB) is an important cause of morbidity and mortality in renal
      transplant recipients. Rifampin has a potent sterilizing activity, but it reduces
      the serum concentrations of the immunosuppressive agents. Moreover, the possible
      contribution made by mycobacterial infection to the incidence of graft rejection
      or renal dysfunction remains unclear. In this study, we investigated the
      recurrence of TB and graft survival duration according to rifampin usage, and we
      evaluated the factors that could influence the duration time until the recurrence
      of TB. Seventy-eight TB patients diagnosed after kidney transplantation were
      studied. Pulmonary TB was diagnosed in 26 of the 78 patients (33.3%), pleural TB
      in 23 (29.5%), combined pulmonary and pleural TB in 5 (6.4%), miliary TB in 19
      (24.4%), and intestinal TB in 2 patients. In the pulmonary (pulmonary TB and
      pleural TB) TB group, no differences in graft survival and the TB free duration
      period were observed between the rifampin usage subgroup and the non- rifampin
      usage subgroup. In the extrapulmonary TB group, no difference was found in mean
      graft survival time between the rifampin usage subgroup and the non-rifampin
      usage subgroup, but the rifampin usage subgroup showed that the TB had a tendency
      to recur later than for the non-rifampin usage subgroup (87 +/- 8 vs. 44 +/- 7
      months, respectively, p=0.30). The factor affecting the duration period until the
      recurrence of TB was the treatment duration (RR=0.761, p=0.030). This study
      suggests that rifampin does not affect graft survival in renal transplant
      recipients in whom immunosuppression is carefully monitored. Also, the study
      results indicate that rifampin may prevent a recurrence of extrapulmonary
      tuberculosis. Prolonged treatment appears to be appropriate for renal transplant
      recipients with TB.

PMID- 15515198
TI  - Proper cut-off value of free to total PSA ratio for detection of prostate cancer
      in Korean men.
AB  - To assess whether the free-to-total prostate specific antigen (PSA) ratio (F/T
      PSA ratio) would enhance prostate cancer detection in Korean men with serum total
      PSA levels between 4 and 20 ng/ml. METHODS: A total of 240 consecutive patients
      whose serum PSA levels were between 4 and 20 ng/ml were enrolled in this two-year
      study. All patients underwent ultrasound-guided transrectal biopsies of the
      prostate gland. The F/T PSA ratio was measured using the Roche immunoassay.
      RESULTS: Of the 240 patients, 202 (84%) had benign histologies, while 38 (16%)
      had prostate cancer. The two patient groups were well matched for age. The mean
      F/T PSA ratio showed a statistically significant difference between the two
      groups: in the benign histology group it was 0.14 (0.04 - 0.37), and 0.10 (0.08 -
      0.20) in the prostate cancer group (p < 0.05). Out of the 183 patients with a PSA
      level between 4-10 ng/ml, the mean F/T PSA ratios were 0.14 and 0.11 in the
      benign histology (n=158) and prostate cancer groups (n=25), respectively (p <
      0.05). From the 57 patients with a PSA level between 10 - 20 ng/ml, the mean F/T
      PSA ratios were 0.14 and 0.10 in the benign histology (n=44) and prostate cancer
      groups (n=13), respectively (p < 0.05). Overall, when the cut-off value of the
      F/T PSA ratio was 0.10, the sensitivity and specificity were 75.0% and 76.5%,
      while for the cut-off value of 0.15 they were 83.3% and 39.7% respectively.
      CONCLUSION: Our data demonstrated the usefulness of the free to total PSA ratio
      in distinguishing benign prostate disease and cancer disease, hence eliminating
      unnecessary biopsies. It is recommended that a cut-off value for the F/T PSA
      ratio of 0.10 be applied to Korean men which this is lower than the value used in
      Western countries.

PMID- 15515199
TI  - A randomized prospective study comparing new vaginal cone and FES-Biofeedback.
AB  - Several different methods of enhancing pelvic floor functions have been developed
      and modified. The aim of this study was to compare the efficacy of a new vaginal
      cone with conventional FES-Biofeedback therapy for female urinary incontinence,
      with respect to pelvic floor rehabilitation. One hundred and twenty patients, who
      required a non-surgical treatment for urinary incontinence, were divided randomly
      into two groups; (1) the Functional Electrical Stimulation (FES)- Biofeedback
      group (or BFB group) and (2) the new vaginal cone group (or cone group). For a
      period of six weeks, two training sessions each week were carried out on the BFB
      group. The new 150-gram dumbbell-shaped vaginal cone, made of fine ceramic
      material, was developed domestically. A therapist instructed patients in the cone
      group upon its use for pelvic floor exercise, and directed the exercise to be
      repeated at home daily; these patients had follow-up visits every week. Objective
      improvements were obvious in both groups. 88.3% and 91.6% of the cone and BFB
      groups showed an improvement after treatment, respectively. There was no
      significant difference in the improvement or dissatisfaction scores of the two
      groups. In conclusion, no significant differences in the therapeutic effects were
      observed between the FES- Biofeedback and the new vaginal cone groups.
      Considering improvements in the quality of life and objective symptoms, the
      therapeutic effects of the two techniques showed no significant differences. The
      new vaginal cone is relatively easy to use at home and aids in pelvic floor
      muscle exercises. Consequently, the new vaginal cone could be used as an
      alternative non-surgical treatment modality in female stress urinary
      incontinence.

PMID- 15515200
TI  - The role of estrogen receptor, progesterone receptor and p53 in development of
      stress urinary incontinence.
AB  - Recent studies have been reported the roles of the estrogen receptor (ER),
      progesterone receptor (PR) and p53 in the development of a pelvic organ prolapse
      (POP). The pathogenesis of stress urinary incontinence (SUI) is related to that
      of POP in the weakness of pelvic support. Therefore, this study was carried out
      to assess the relationship between ER, PR, p53 and the development of SUI, and to
      elucidate the biomolecular pathophysiology of SUI. The periurethral fascia was
      obtained from 6 menopausal patients diagnosed with SUI and 10 menopausal patients
      without SUI who visited the Department of Obstetrics and Gynecology, Severance
      Hospital, Seoul, Korea. The relative ER, PR and p53 protein levels in the
      periurethral fascia were obtained by western blot analysis and densitometry. A
      Mann-Whitney U test was used for statistical analysis (p < 0.05). The mean age
      (+/- SD) of the 16 patients was 59.0 +/- 5.5 years (range, 50-74 years). The mean
      body mass index was 25.2 +/- 2.7 kg/m2 (21.8 - 30.8) and the average number of
      vaginal deliveries was 2.8 +/- 1.9 (1.0 - 9.0). The ER level (0.33 +/- 0.17 vs.
      1.86 +/- 0.83, p= 0.02) and the p53 level (1.25 +/- 0.67 vs. 4.71 +/- 2.40, p=
      0.01) were lower in the experimental group. However, the PR level of the two
      groups were similar (0.64 +/- 0.13 vs. 0.48 +/- 0.33, p=0.56). The p53 and ER
      levels were significant lower in the study group. This suggests that p53 and ER
      might be important factors in the development of SUI. Further prospective studies
      about the association of ER, p53 and SUI will be needed to elucidate the
      molecular pathogenesis of SUI.

PMID- 15515201
TI  - Comparison of phenotypic characterization between "alginate bead" and "pellet"
      culture systems as chondrogenic differentiation models for human mesenchymal stem
      cells.
AB  - Chondrogenesis involves the recruitment of mesenchymal cells to differentiate
      into chondroblasts, and also the cells must synthesize a cartilage-specific
      extracellular matrix. There were two representative culture systems that promoted
      the chondrogenic differentiation of human mesenchymal stem cells. These systems
      were adaptations of the "pellet" culture system, which was originally described
      as a method for preventing the phenotypic modulation of chondrocytes, and the
      "alginate bead" culture system, which was used to maintain encapsulated cells at
      their differentiated phenotype over time, and also it was used to maintain the
      cells' proteoglycan synthesis at a rate similar to that of primary chondrocytes.
      We performed test on the differences of phenotypic characterization with the two
      methods of differentiating human mesenchymal stem cells into chondrocytes. The
      typical gene for articular cartilage, collagen type II, was more strongly
      expressed in the "alginate bead" system than in the "pellet" culture system, in
      addition, specific gene for hypertrophic cartilage, collagen type X, was more
      rapidly expressed in the "pellet" system than in "alginate bead" culture system.
      Therefore, the "alginate bead" culture system is a more phenotypical, practical
      and appropriate system to differentiate human mesenchymal stem cells into
      articular chondrocytes than the "pellet" culture system.

PMID- 15515202
TI  - Comparison of femoral geometry among cases with and without hip fractures.
AB  - Hip fractures have high morbidity and mortality rate for the people as a
      complication of osteoporosis and is generally seen in old age. It is known that
      femoral geometric measurements are important in the assessment of hip fracture
      risks. This study aimed to examine the association between hip geometry and hip
      fracture in post-menopausal elderly females. In the present study, 232 hip X-rays
      were taken from women with no hip fractures (Group 1) and 29 post-menopausal
      women with hip fractures (Group 2) after a minor trauma. After standard anterior
      posterior plain pelvic X-ray radiographs were obtained, various radiographic
      measurements were performed in all cases, including the hip axis length (HAL),
      femoral neck axis length (FAL), acetabular width (AW), femoral head width (HW),
      femoral neck width (FW), femoral shaft width (FSW), intertrochanteric width (TW),
      lateral and medial cortical thickness of the femoral shaft (LCT, SMCT), femoral
      neck cortical thickness (NMCT) and femoral neck-shaft angle (Q-angle). In group
      1, the mean age, weight and height were 62.5 +/- 7.4 years, 70.8 +/- 12.5 kg, and
      157.5 +/- 6.7 cm, respectively. In group 2, these values were 70.17 +/- 6.8
      years, 64.7 +/- 11.5 kg, and 158.3 +/- 2.7 cm, respectively. There were no
      statistically significant differences in the measurements of HAL, FAL, AW and HW
      between the two groups. In group 2, the mean FW value was significantly higher
      than in group 1 (p= 0.01). The mean values for FSW, TW, NMCT, SMCT, LCT were
      statistically lower in group 2 than those in group 1 (p= 0.01, p=0.038, p=0.001,
      p < 0.001, p < 0.001, respectively). Q-angle was also significantly higher in
      cases with hip fracture than in cases with no hip fracture (p=0.01). The values
      of FW, FSW, TW, NMCT, SMCT, LCT and Q-angle seem to be important parameters in
      the evaluation of hip fracture risks. However, further studies are needed to
      clarify this conclusion.

PMID- 15515203
TI  - Apoptotic change in response to magnesium therapy after moderate diffuse axonal
      injury in rats.
AB  - The biochemical factors related to moderation of secondary or delayed damage to
      the central nervous system (CNS) remain undefined. We have recently demonstrated
      that the weight- drop induced moderate diffuse axonal injury (mDAI) in rats
      causes a rapid decline in serum ionized magnesium (Mg(2+)) and a significant
      increase in the amount of serum ionized calcium (Ca(2+)) relative to Mg(2+)
      (Ca(2+)/ Mg(2+)). For three hours, serum Mg(2+) levels remained significantly
      depressed at 76% of preinjury values (p < 0.05), but total serum magnesium
      remained unchanged (tMg, p > 0.05). Head trauma resulted in a small decrease of
      Ca(2+) (about 10%), but a significant increase in the amount of Ca(2+)/Mg(2+)
      (mean value in control group: in injured group for 3 hours after trauma =4.65 +/-
      0.012 : 5.69 +/- 0.015, p < 0.05) was observed. In order to further investigate
      the relationship between Mg(2+) and brain injury, the effect of Mg(2+) treatment
      on posttraumatic histological changes (apoptotic changes) was examined following
      the weight-drop induced brain injury. At 30 min postinjury, animals treated with
      MgSO(4) (750 micromol/kg) showed significant improvements of apoptotic changes
      when compared to the control group (54.8 +/- 1.7, 51.5 +/- 3.2 at 12, 24 h in
      control group, 24.8 +/- 2.6, 20.5 +/- 1.4 at 12, 24 h in treated group, p <
      0.05). The early decline in serum Mg(2+) and the increase in the amount of
      Ca(2+)/Mg(2+) immediately following brain trauma uncovered by these findings
      suggest that they may be a critical factor in the development of irreversible
      tissue injury. If this proves to be the case, treatment with MgSO(4) may be
      effective in improving histological findings following experimental traumatic
      brain injury in rats.

PMID- 15515204
TI  - Fasting-induced down-regulation of NADPH-diaphorase in the magnocellular PVN of
      rats.
AB  - In this study, we examined if glucocorticoids are required for the fasting
      induced decrease of neuronal nitric oxide synthase (nNOS) in the magnocellular
      division of the paraventricular nucleus (PVN). Rats were adrenalectomized,
      subjected to 48 h of food deprivation with/without dexamethasone (5 mg/ kg, 4
      subcutaneous injections with 12 h intervals), and the brain slices were processed
      for NADPH-diaphorase (NADPH- d) staining, a histochemical marker for nNOS in
      neuronal cells. In food deprived adrenalectomized rats, but not in free fed
      intact rats, dexamethasone significantly decreased NADPH-d staining in the
      magnocellular PVN. We previously reported that food deprivation decreases nNOS in
      the magnocellular PVN of intact rats. Thus, the present results together with our
      previous report suggest that although glucocorticoids are required for fasting
      induced nNOS down-regulation in the magnocellular PVN, glucocorticoids may not be
      directly involved and some other molecular signals produced by food deprivation
      may play a pivotal role over glucocorticoid in the regulatory pathway for nNOS
      expression in this brain region.

PMID- 15515205
TI  - A systemic lupus erythematosus patient with protein losing enteropathy.
AB  - Protein-losing enteropathy (PLE) is a rare manifestation of systemic lupus
      erythematosus (SLE), and it is an uncommon cause of hypoalbuminemia without
      proteinuria. We describe a case of an 11 year-old girl who had diarrhea and
      periorbital edema as the initial symptoms of SLE. PLE was diagnosed by 24-hour
      stool alpha-1 antitrypsin clearance and (99m)Tc-human serum albumin scintigraphy.

PMID- 15515206
TI  - Identification of a dysferlin gene mutation in a Korean case with Miyoshi
      myopathy.
AB  - Recent genetic and immunohistochemical analyses have shown that Miyoshi myopathy
      (MM) is caused by a mutation in the DYSF gene, which induces dysfunction of
      dysferlin. The author described one patient showing characteristic MM phenotype
      with deficiency of dysferlin on immunohistochemistry. Direct DNA sequencing of
      whole exons of DYSF gene revealed one homozygous missense mutation (G1165C) on
      exon 12, which let to an amino acid substitution from the glutamic acid to
      glutamine at the 389 of the peptide sequence in this patient. This is the first
      reported case of MM confirmed by immunohistochemical and genetic analyses in
      Korea.

PMID- 15515207
TI  - Familial isolated noncompaction of the ventricular myocardium in asymptomatic
      phase.
AB  - Isolated noncompaction of the ventricular myocardium (INVM) is a rare
      cardiomyopathy resulting from a failure of normal endomyocardial embryogenesis
      and it has been categorized as a form of unclassified cardiomyopathy. The
      disorder is characterized by an excessively prominent trabecular meshwork with
      deep intertrabecular recesses. Although the disorder is sporadic, familial
      incidence may occur. Clinical symptoms and prognosis of INVM may differ markedly,
      and range from an asymptomatic course to a severe cardiac disability. The
      diagnostic method of choice for IVNM is echocardiography, which reveals multiple
      prominent trabeculations with deep intertrabecular spaces communicating with the
      left ventricular cavity in the middle and apical segments of the left ventricle.
      The authors report a case of INVM in a family in which three adult members (a
      brother and two sisters) were found to be affected by this disorder. They were
      all asymptomatic. The diagnosis of the disorder was made first in the 36-year-old
      brother by transthoracic echocardiography (TTE) and multidetector CT (MD CT),
      during the process of preoperative evaluation for surgical treatment of low back
      intervertebral herniated disc. TTE and MD CT showed similar and peculiar findings
      of INVM. Echocardiographic screening in all first-degree relatives of this
      patient, in order to identify asymptomatic patients, demonstrated INVM in two
      elder sisters.

PMID- 15515208
TI  - Subacute bacterial endocarditis associated with upper endoscopy.
AB  - Transient bacteremia associated with various endoscopic procedures is a well
      documented phenomenon. Clinically important bacteremias are very rarely seen,
      however, this malady has significant morbidity in susceptible patients with
      valvular heart disease, liver cirrhosis, malignancy and immune deficiency. This
      bacteremia is a complication that is generally observed secondary to upper
      endoscopy and other associated invasive procedures in at risk patients, and the
      more serious manifestations include spontaneous bacterial peritonitis, septic
      arthritis, meningitis, brain abscess and infective endocarditis. Infective
      endocarditis is an extremely rare complication of gastrointestinal endoscopy, and
      it has been convincingly documented in only seven cases. We report a case of
      native valve endocarditis due to Streptococcus intermedius in a patient with
      valvular heart disease as a consequence of routine upper endoscopy.

PMID- 15515209
TI  - Collagenous fibroma (desmoplastic fibroblastoma).
AB  - A Collagenous Fibroma (Desmoplastic Fibroblastoma) is a rare, benign, slowly
      growing, fibroblastic, soft tissue lesion. Here, the case of a 28-year-old woman,
      who presented with a 1-year history of a slowly growing painless mass in the
      right anterior aspect of her neck, is described. This type of tumor was first
      described by Evans in 1995, and named as a Desmoplastic fibroblastoma but was
      renamed, by Nielsen in 1996 as a Collagenous Fibroma. This type of tumor is
      frequently reported in men with a mean age at occurance of 50 years. Clinically,
      a Collagenous fibroma presents as a firm, well-circumscribed subcutaneous, or
      intramuscular, painless mass of long duration. They are mostly located in the
      neck and extremities. The tumors range in size from 1 to 20 cm and predominantly
      occurs within the subcutaneous tissue, but fascial and skeletal muscle
      involvement is common. The treatment of a Collagenous Fibroma is a total surgical
      excision. No tumor recurrence has been reported the literature during the follow
      up period and no tumor recurrence was observed in our case at the 1-year follow
      up.

PMID- 15515210
TI  - Renal involvement of chronic myelogenous leukemia presenting as a kidney tumor.
AB  - Renal involvement by leukemic cells is rare in chronic myelogenous leukemia
      (CML). Herein, this study reports a case of CML associated with renal involvement
      of leukemic cells, which occurred 1 and 1/2 years after the initial diagnosis.
      Abdomino-pelvic computed tomography revealed a 4.4 x 4.2 cm-sized, low-density
      solid mass having a thick wall from the mid to lower pole of the left kidney. A
      peripheral blood analysis revealed blastic transformation of CML. The biopsied
      renal parenchyme was diffusely infiltrated by sheets of immature myeloid cells,
      polymorphonuclear leukocytes, and occasional eosinophils. Most of the
      infiltrating cells were positive for anti-neutrophil elastase, but negative for
      lymphoid markers. Therefore, differential diagnosis of a kidney tumor during the
      course of CML, especially in the time of blastic transformation, should be
      performed.

PMID- 15515211
TI  - Congenital absence of inferior vena cava as a rare cause of pulmonary
      thromboembolism.
AB  - Interruption of the inferior vena cava (IVC) with azygos continuation is an
      uncommon vascular anomaly that results from aberrant development during
      embryogenesis. We report a rare case of this anomaly, presenting with massive
      pulmonary embolism. Subsequent evaluation with abdominal CT scan revealed the
      congenital absence of retrohepatic IVC. The patient was successfully treated with
      anticoagulation. When deep venous thrombosis (DVT) develops in patients with no
      apparent risk factors, the presence of congenital IVC anomalies should be
      considered.

PMID- 15515212
TI  - Santorinicele containing a pancreatic duct stone in a patient with incomplete
      pancreas divisum.
AB  - Santorinicele, a focal cystic dilatation of the distal duct of Santorini, has
      been suggested as a possible cause of the relative stenosis of the accessory
      papilla, is associated with complete pancreas divisum, which results in acute
      episodes of pancreatitis or pain. This report describes a case of a
      santorinicele, which was initially detected by upper gastrointestinal endoscopy
      as a polypoid mass, in a patient with recurrent abdominal pain. The mass was
      subsequently proved to be a santorinicele containing a pancreatic duct stone
      associated with incomplete pancreas divisum on endoscopic retrograde
      pancreatography. To the best of our knowledge this is believed to be the first
      description of a santorinicele associated with these characteristic findings.

PMID- 15515213
TI  - Coexistence of Darier's disease and acrokeratosis verruciformis of Hopf.
AB  - Darier's disease and acrokeratosis verruciformis are inherited with the same
      pattern and they share similar clinical properties. We present a patient with
      both Darier's disease and acrokeratosis verruciformis. The patient had had
      brownish and skin-colored papules, initially on her face and neck, since the age
      of 25. Similar lesions had gradually spread to various parts of her body and
      lastly the dorsal aspect of her feet. On dermatological examination, brownish and
      skin-colored, 2 to 5 mm, keratotic papules were observed on her face, neck, both
      axillae, inframammary regions, and dorsa of the hands and feet. The nail
      examination revealed "V" shaped notches and longitudinal ridges on the fingers of
      both hands. The biopsy taken from the neck showed typical findings for Darier's
      disease. The biopsy from the dorsa of the left foot revealed the distinctive
      structures of acrokeratosis verruciformis. In this article the clinical and
      histopathological findings of these diseases are reviewed based on our patient.

PMID- 15515214
TI  - Tissue transglutaminase autoantibodies in patients with IgM rheumatoid factors.
AB  - The recent identification of tissue transglutaminase (tTG) as the autoantigen for
      celiac disease-associated anti-endomysial antibodies (EMA) has allowed the use of
      rapid immunoassay to detect the presence of autoantibodies, anti-tTG, in the
      serum of patients. In this study, we examined the prevalence of IgG or IgA anti
      tTG in sera from patients with elevated levels of IgM rheumatoid factors, which
      are autoantibodies reactive with the Fc portion of IgG. We report here on four
      cases of anti-tTG positivity for patients with elevated IgM rheumatoid factor
      (RF) without evidence of celiac sprue. The study population consisted of 65
      patients (26 men, 39 women; mean age, 49 years; range 4 - 92 years) with elevated
      RF (>20 U/ml ), and 23 healthy subjects (12 men, 11 women; mean age, 46 years;
      range, 21 - 54 years). IgG and IgA anti- tTG levels were detected using a
      commercially available ELISA kit (Immuno-Biological Laboratories, Germany). Out
      of 65 patients, one (1.5%) and three (4.6%) patients were positive for IgG and
      IgA anti-tTG antibodies, respectively, and this was a higher frequency than
      occurred in healthy subjects (0/23). The clinical features of the four cases
      positive for IgG or IgA anti-tTG were as follows: The first case (female, 63 yrs)
      positive for IgA anti-tTG antibody suffered from rheumatoid arthritis, type II
      diabetes mellitus, iron deficiency anemia and gastric indigestion without
      symptoms of malabsorption. She denied any gluten sensitivity on her diet. Her
      esophagogastroduodenoscopic biopsy showed mucosal atrophy with no elongated
      crypts or infiltration of inflammatory cells in the lamina propria. The remaining
      three cases positive for anti-tTG antibodies had interstitial pneumonia, a
      herniated lumbar disc, and mild scoliosis, respectively. They all denied any
      malabsorption symptoms or gluten sensitivity. Jejunal biopsy could not be
      performed in all four cases.

PMID- 15515215
TI  - [Sentinel lymph node reevaluation].

PMID- 15515216
TI  - Pro/con clinical debate: steroids are a key component in the treatment of SARS.
      Con: No, steroids are not a key component of the treatment regimen for SARS.

PMID- 15515217
TI  - Fluid resuscitation in the intensive care unit.

PMID- 15515218
TI  - Fluid resuscitation in the intensive care unit.

PMID- 15515219
TI  - Fluid resuscitation in the intensive care unit.

PMID- 15515220
TI  - Fluid resuscitation in the intensive care unit.

PMID- 15515221
TI  - Arterial thrombosis in systemic lupus erythematosus.

PMID- 15515222
TI  - Drug therapy in Alzheimer's disease.

PMID- 15515223
TI  - Drug therapy in Alzheimer's disease.

PMID- 15515224
TI  - Sweet candy, bitter poison.

PMID- 15515225
TI  - Farm chore checkup.

PMID- 15515226
TI  - National meeting breaks the mold.

PMID- 15515227
TI  - Sister study launched nationwide.

PMID- 15515228
TI  - Should all coronary angiographies be accompanied by a renal arteriogram (and
      stent)? The argument against.

PMID- 15515229
TI  - End-of-life decisions: a failure to communicate.
AB  - Lustig relates the importance of knowledge in bioethics and effective
      communication between patient and caregivers in dealing with dilemmas involved
      with therapy and end-of-life choices. He claims that it is necessary that the
      medical school curricula should incorporate specific strategies for better
      clinical communication, which may reduce the number of dilemmas encountered by
      professionals.

PMID- 15515230
TI  - Separated after birth.
AB  - Bioethics has developed against a backdrop of increased concern for human and
      civil rights, including the rights of patients to decide about their own
      treatment. The recent case of Laleh and Ladan Bijani, the twenty-nine-year old
      Iranian conjoined twins who died in a Singapore hospital on Jul 8, after more
      than fifty hours of surgery aimed at separating them, highlights the tensions
      between respect for patient autonomy and professional medical judgment.

PMID- 15515231
TI  - Immortality.
AB  - In December, the President's Council on Bioethics released Beyond Therapy:
      Biotechnology and the Pursuit of Happiness. Here, Lustig discusses the six-part
      report that provides a balanced but critical assessment of actual and prospective
      developments in biotechnology and seeks to anchor its discussion in shared moral
      and metaphysical concerns--the nature of human nature, and the social and
      political implications of unfettered choices in altering the human prospect
      through biotechnology.

PMID- 15515232
TI  - Beyond a western bioethics?
AB  - Like theology and ethics generally, bioethics has increasingly developed a global
      consciousness. Controversies over AIDS research and access to affordable AIDS
      treatment have generated new awareness about the importance of international
      collaboration as well as the difficulty of achieving moral consensus across
      economic, political, and cultural divides. Advances in scientific and medical
      knowledge through initiatives such as the Human Genome Project invite new
      questions about the nature of health care as a common good. This budding global
      consciousness serves as a starting point for examining contemporary challenges to
      the secular, principle-based Western bioethics that has dominated national and
      international debate for three decades.

PMID- 15515233
TI  - Spider venom helps researchers elucidate role of acidosis in stroke.

PMID- 15515234
TI  - Good fats prevent dendritic damage in mouse model of AD.

PMID- 15515235
TI  - Utrophin therapy for Duchenne muscular dystrophy?

PMID- 15515236
TI  - Active HERV protein implicated in demyelination.

PMID- 15515237
TI  - How NSAIDs might prevent Alzheimer's disease.

PMID- 15515238
TI  - Astrocyte involvement in cerebral-blood-flow regulation.

PMID- 15515239
TI  - Absence of Cajal bands short changes Schwann cells.

PMID- 15515240
TI  - Preventable rabies deaths because of wrong vaccine.

PMID- 15515241
TI  - New therapy for medulloblastoma tested in mice.

PMID- 15515243
TI  - Recent publications in hematological oncology.

PMID- 15515242
TI  - Neuron death due to unfolded protein response in gangliosidosis.

PMID- 15515244
TI  - SARS patients and need for treatment.

PMID- 15515245
TI  - Occupational malaria following needlestick injury.

PMID- 15515246
TI  - Nosocomial transmission of dengue.

PMID- 15515248
TI  - Influenza among U.K. pilgrims to hajj, 2003.

PMID- 15515249
TI  - Streptomyces thermovulgaris bacteremia in Crohn's disease patient.

PMID- 15515250
TI  - Human West Nile virus, France.

PMID- 15515251
TI  - SARS in teaching hospital, Taiwan.

PMID- 15515252
TI  - Boiling and Bacillus spores.

PMID- 15515253
TI  - [Cervicofacial actinomycosis in 3 children].

PMID- 15515255
TI  - Flawed choices.

PMID- 15515259
TI  - Opening doors of perception. Creativity, learning and developing practice.
AB  - The notion of'intelligence and humane choice' is addressed in this article. The
      only way nursing can be influential in the world of healthcare is questioned by
      looking at a commitment to learning, development and research. The article aims
      to challenge issues about nurse education and explore ways in which the nursing
      profession can move debates about the values underpinning the preparation of
      undergraduate nurses.

PMID- 15515260
TI  - An ethical dilemma. Is it ever acceptable to lie to a patient?
AB  - Ethical decision-making, and the choice of whether or not to be truthful, is an
      important part of everybody's life. For nurses, decisions such as these are made
      every day and affect not just themselves, but also the lives of others. This
      article will examine the ethics of truth-telling from the point of view of a
      theatre nurse dealing with a seriously ill patient.

PMID- 15515261
TI  - The hazards of diathermy plume. Part 2. Producing quantified data.
AB  - Laser and electrocautery devices used during surgery produce smoky emissions that
      may contain vapours and particulate aerosols, which can have a chemical and
      biological impact on those exposed. A group of theatre staff and specialist
      nurses at Rotherham District General Hospital got together to draw up a risk
      assessment into the possible occupational exposure of theatre staff, with a view
      to eliminating or controlling these hazards as far as possible.

PMID- 15515262
TI  - The role of the link lecturer in the perioperative environment.
AB  - As a result of the demise of the two-tier system of clinical teacher and
      lecturer, all teachers were assigned to clinical areas in which they facilitate
      the development of an educational milieu to support student learning in practice.
      This article highlights the role of the link lecturer within the perioperative
      environment. It focuses on how this multi-faceted position can assist students to
      link theory and practice, and addresses key issues relating to mentorship,
      clinical credibility and educational audit.

PMID- 15515263
TI  - Job descriptions and job matching.
AB  - As the date for national roll-out and the implementation for Agenda for Change
      draws near, many of you will be involved in the job matching process. This is
      designed to measure your job against a national job profile, thus establishing
      which pay band you will be placed in and so determining your salary.

PMID- 15515264
TI  - Analytical methods for the determination of alkylphenolic surfactants and
      polybrominated diphenyl ethers in wastewaters and sewage sludges. II method
      development.
AB  - Analytical methods for the determination of two groups of compounds, the non
      polar alkyl phenols along with their more polar ethoxylates, and the hydrophobic
      polybrominated flame retardants in wastewater samples have been developed. The
      methods allow for determination of the analytes in both the aqueous and solid
      phases, which were separated by centrifugation and filtration. Extraction from
      the aqueous phase involved the use of SPE for the surfactants, however, liquid
      liquid extraction was found to be more efficient for the PBDE. Alkyl phenols and
      their ethoxylates were extracted from the solid phase by shaking with solvent and
      Soxhlet was used for extraction of PBDE. Sample cleanup was based on alumina
      columns for the PBDE and surfactants when extracted form solids. Quantification
      of surfactants utilised LC-MS with ESI in both positive and negative ionisation
      mode, and GC-MS (NCI) was used to determine the PBDE, with the exception of the
      deca congener, where a 10 m column installed on GC-ECD resulted in short run
      times and reduced thermal decomposition. Method recoveries for the surfactants
      were above 80%, and for PBDE 92.5% from the solid phase and 95+/-5% from the
      liquid phase.

PMID- 15515265
TI  - Adsorption of dyes using peat: equilibrium and kinetic studies.
AB  - In recent years, adsorption has been accepted as one of the most appropriate
      processes for decolorization of wastewaters. This paper presents experimental
      results on application of peat for removal of structurally diverse dyes (azo,
      oxazine, triphenylmethane, thiazine and others) with emphasis on relevant factors
      such as the adsorbate-adsorbent chemical properties and chemical interaction as
      well as adsorption conditions. The equilibrium experimental results were fitted
      to Langmuir and Freundlich isotherms to obtain the characteristic parameters of
      each model. According to the evaluation using the Langmuir equation, the maximum
      sorption capacity of basic dyes at 22 degrees C was 667 (mg g(-1)) for Basic Blue
      24, 526 (mg g(-1)) for Basic Green 4 and 714 (mg g(-1)) for Basic Violet 4. On
      the other hand for Acid Black 1 it was only 25 (mg g(-1)). Batch kinetics studies
      were undertaken and the data evaluated in compliance with chemical sorption
      mechanisms. For all of the systems studied the pseudo-second order model provided
      the best correlation of the kinetic experimental data. A film-pore double
      resistance diffusion model for mass transfer has also been used in this study to
      determine the effective diffusivity, Deff, for the adsorption of basic dyes in to
      peat.

PMID- 15515266
TI  - Quality of individual domestic greywater streams and its implication for on-site
      treatment and reuse possibilities.
AB  - A sampling campaign was conducted in order to characterise the quality and
      quantity of individual domestic greywater streams. Based on the results, various
      scenarios of inclusion and / or exclusion of different greywater streams were
      explored, and their implication for on-site greywater treatment and reuse options
      are discussed. Domestic greywater was found to contribute as much as 55-70% of
      the specific daily load of TSS and BOD, in municipal sewage. The kitchen sink was
      signalled out as a major contributor of VSS, CODt, and BODt with 58%, 42% and
      48%, of their total daily load respectively. The washing machine was established
      as a significant contributor of sodium, phosphate and CODt (40%, 37% and 22% of
      the total load). The dishwasher, although contributing only 5% of the flow, was
      found to be a significant contributor of phosphate and boron. The wash basin was
      found to be the least polluting appliance. As "demand" for greywater within the
      urban environment is lower than its "production", it is logical to recycle only
      the less polluted greywater streams. In order to explore the consequences of the
      above concept on discharge volume, pollutants loads and concentrations, 18
      scenarios were studied, in each at least one stream was excluded from the
      combined greywater stream. Exclusion of the joined stream of the kitchen sink
      plus the highly polluted streams of the washing machine (wash + 1st rinse) and
      dishwasher (pre-rinse + wash) significantly improved greywater quality, with the
      advantage of leaving enough greywater to be reused (65-70 l/c/d).

PMID- 15515267
TI  - Breakthrough curves and column design parameters for sorption of lead ions by
      natural zeolite.
AB  - Sorption of lead ions, by natural phillipsite (zeolite) has been studied in a
      laboratory-scale packed-bed column. Breakthrough curves were obtained under
      different operating conditions. Bed depth- service time (BDST) model was applied
      and parameters for column design were determined for lead ions at 5% breakthrough
      yielding BDST sorption capacity of 24.27-35.73 mg x g(-1), rate constant 2.80 x
      10(-4) - 4.16 x 10(-4) dm3 x mg(-1) x min(-1), critical bed depth 4.02-10.37 cm
      and sorbent exhaustion rate of 12-51.3 g zeolite per dm3 of treated solution over
      a flow-rate range of 14.15-36.80 cm x min(-1). Breakthrough times at C/Co = 0.05
      ranged from 5-100 min depending on flow rate and bed depth. External mass
      transfer is rate limiting in the initial stages of adsorption as indicated by
      agreement between Wolborska model and the experimental data in the low C/Co
      region of the breakthrough curve.

PMID- 15515268
TI  - A new tool for in situ measurements of the vertical distribution of magnetic
      susceptibility in soils as basis for mapping deposited dust.
AB  - In situ measurements of magnetic susceptibility of topsoils are commonly used for
      mapping the spatial distribution of atmospherically deposited ferrimagnetic
      particles. However, the surface measurements integrate signal from certain soil
      volume and, thus, it is not evident how deep is the magnetically enhanced layer,
      if there is such. This information is often required for detailed sampling.
      Furthermore, fast estimate of the significance of lithogenic contribution is
      needed for the proper interpretation of the surface data. This can be reliably
      done on the basis of vertical distribution of magnetic susceptibility of a soil
      column. Until now, there was practically no reliable, fast and sensitive enough
      tool to carry out these measurements in real time, directly in field. In this
      paper, we report on a new soil-profile kappameter SM400, which enables continuous
      real-time measurements, performed directly in the field. We describe its basic
      measurement principles. Performance parameters are discussed, showing that
      sensitivity is high enough to depict the soil layers with different
      susceptibility and a data density of 6 points per 1 mm of depth, which results in
      smooth curves of susceptibility, unlike field or laboratory probes used until
      now. Profiles acquired using different probes and instruments are compared in
      order to demonstrate advantages of the new approach.

PMID- 15515269
TI  - Lignor process for acidic rock drainage treatment.
AB  - The process using lignosulfonates for acidic rock drainage (ARD) treatment is
      referred to as the Lignor process. Lignosulfonates are waste by-products produced
      in the sulfite pulping process. The present study has shown lignosulfonates are
      able to protect lime from developing an external surface coating, and hence to
      favor its dissociation. Further, the addition of lignosulfonates to ARD solutions
      increased the dotting and settling rate of the formed sludge. The capability of
      lignosulfonates to form stable metal-lignin complexes makes them very useful in
      retaining metal ions and thus improving the long-term stability of the sludge
      against leaching. The Lignor process involves metal sorption with
      lignosulfonates, ARD neutralization by lime to about pH 7, pH adjustment with
      caustic soda to 9.4 - 9.6, air oxidation to lower the pH to a desired level, and
      addition of a minimum amount of FeCl3 for further removal of dissolved metals.
      The Lignor process removes all concerned metals (especially Al and Mn) from the
      ARD of the Britannia Mine (located at Britannia Beach, British Columbia, Canada)
      to a level lower than the limits of the B.C. Regulations. Compared with the high
      density sludge (HDS) process, the Lignor process has many advantages, such as
      considerable savings in lime consumption, greatly reduced sludge volume, and
      improved sludge stability.

PMID- 15515270
TI  - Comparison of different carbon sources for ground water denitrification.
AB  - This study presents a comparison of denitrification rates and denitrification
      stoichiometry when using different sources of carbon. Denitrification tests were
      carried out in test bottles containing water and soil samples acquired at a
      nitrate-contaminated site and supplemented with either sucrose, acetate or
      ethanol. The tests demonstrated nitrate removal in all carbon source supplemented
      bottles. The rate of denitrification and the required amount of a carbon source,
      however, depended on the choice of substrate. Ethanol and acetate were found to
      provide the highest denitrification rate, that of 1.4 - 1.6 mg-N l(-1) d(-1).
      Sucrose-supplemented bottles demonstrated a significantly slower denitrification
      rate, that of 0.6 - 0.9 mg-N l(-1) d(-1). In addition to slow denitrification
      rates, sucrose-supported denitrification required more carbon source.

PMID- 15515271
TI  - Wastewater sludge convective drying: influence of sludge origin.
AB  - This paper deals with thermal drying of wastewater sludges, whose management will
      become crucial in the forthcoming years. Sludges collected after mechanical
      dewatering in 5 different WWTPs are submitted to the same convective drying
      treatment in order to try finding some relations between the drying behaviours,
      the type of effluent and wastewater treatments. Results show dearly sludge drying
      remains a particularly complex operation because sludges may exhibit very
      different behaviours, both from kinetic and texture points of view. Initial
      moisture content and global composition are not sufficient to explain the
      different observed behaviours. It is too early to claim one or another type of
      water treatment has an influence on the drying behaviour. However, the drying
      rates can be classified in the inverse order of the organic content. Moreover for
      sludges at the same siccities, the harder the material (rheological properties),
      the higher the drying rate. Final textural properties can be related to the
      rheological properties and the internal diffusion limitations lowering the drying
      intensity.

PMID- 15515272
TI  - [Heavy metals in water of the Skikda Bay].
AB  - The region of Skikda is one of the most important industrial poles of Algeria.
      The aim of the study is a qualitative and quantitative evaluation of the
      pollution by heavy metals of the marine water of the bay. The pollutants
      investigated are lead, cadmium and mercury because of their toxicity. The study
      is concerned mainly with the spatiotemporal evolution of the pollution on the
      extent of the bay. Concentrations of heavy metals metals vary from 4 microg l(-1)
      to 55 microg l(-1) for lead, 1 microg l(-1) to 17 microg l(-1) for cadmium and
      0,1 to 1,1 microg l(-1) for mercury, which indicates a beginning of pollution of
      the site. Only small variation of the contents have been noted in a second
      investigation carried out one decade after the first one.

PMID- 15515273
TI  - Equilibrium, kinetic and mass transfer studies and column operations for the
      removal of arsenic(III) from aqueous solutions using acid treated spent bleaching
      earth.
AB  - In the present study, a new adsorbent was produced from spent bleaching earth by
      H2SO4 impregnation method. The sorption of arsenic(III) by acid treated spent
      bleaching earth was studied to examine the possibility of utilizing this material
      in water treatment systems. The effect of time, pH, initial concentration,
      temperature on the adsorption of arsenic(III) was studied. Maximum adsorption was
      found to occur at pH 9.0. The adsorption process followed the first order
      Lagergren equation. Mass transfer coefficients and rate constants of
      intraparticle diffusion were calculated. The experimental data points were fitted
      to the Langmuir equation in order to calculate the adsorption capacity (Q0) of
      the adsorbent and the value of Q0 was found to be 0.46 mmol g(-1). In order to
      understand the adsorption mechanism, Dubinin-Radushkevich (DR) isotherm was used.
      The magnitude of E calculated from DR equation was found to be 5.12 kJ mol(-1).
      The heat of adsorption (deltaH0 = -30367 J mol(-1)) implied that the adsorption
      was physical exothermic adsorption. The column studies were also carried out to
      simulate water treatment processes. The capacity values obtained in column
      studies were found to be greater than the capacity values obtained in batch
      studies. This result was explained by the difference between batch system and
      column system. The factors that affect the capacity values of column and batch
      systems were explained. The effect of other anions on the adsorption of
      arsenic(III) in the presence of NO3-, SO4(2-), Cl-, Br- was studied. The presence
      of these anions did not affect the adsorption of arsenic(III) significantly.

PMID- 15515274
TI  - Estimation of spilled hydrocarbon volume--the state-of-the-art.
AB  - With the increase in the environmental awareness and reorganization of the need
      for its protection, the study of soil and groundwater contamination and its
      remediation have become the focus of numerous researchers. Intentional and
      unintentional release of hydrocarbon into soil and subsurface pose a great threat
      to the biosphere environment. The quantification of spilled volume has primary
      importance for carrying out the remediation work and is considered a first step
      in the remediation hierarchy. Different investigators approached the problem from
      many viewpoints, and the resulting achievements are so extensive and scattered
      that it seems essential to inventory the completed works. This paper presents a
      systematic study of the available experimental and theoretical works. A complete
      picture of the present status of the problem is also provided. Issues that remain
      unresolved and obscure by the current day investigators are pointed out to
      facilitate future research directions and more comprehensive analyses of the
      quantification of spilled hydrocarbon volumes.

PMID- 15515275
TI  - Trihalomethane determination and removals from the main discharge channel of
      Konya City (Turkey).
AB  - Konya Main Discharge Channel is a very important environmental problem due to
      carrying the domestic waste water of Konya city centre as well as industrial
      waste water. Lowest flow rate of the channel was observed in October about 2
      10(4) m3d(-1). In this period, channel water is not only waste water but includes
      more rain water coming from Golyazi region. Discharge channel water can only
      reach to Tuz Lake for three months in a year. At other times of the year, water
      cannot reach the lake because of high evaporation, infiltration and usage of the
      water for irrigation. The land irrigated with the waste water tends to lose its
      productivity. In this study, water samples were collected and analysed from one
      hourly period for 2 days (24 x 2 = 48), daily period for 3 weeks (7 x 3 = 21) and
      monthly samples for a year (9 months). The samples were analysed as to whether
      these contained trihalomethanes or not, also results were compared with
      disinfection method that is used for drinking water, and samples were collected
      from ten different points on the channel. Pollution level of the channel water
      was controlled in accordance with the Turkish Water Pollution Control Law. In
      addition to trihalomethanes analysis, the effect of aeration on trihalomethanes
      was investigated. Collected samples (given above) were analysed for
      trihalomethanes compounds, and the relationship between disinfection type and
      dosage method on trihalomethanes formation was compared in this study.

PMID- 15515277
TI  - Reader comments on radiation-induced xerostomia.

PMID- 15515278
TI  - Advanced nursing certification to become role specific.

PMID- 15515279
TI  - Venous thromboembolism in patients with cancer. Part I. Survey of oncology
      nurses' attitudes and treatment practices for ambulatory settings.
AB  - Patients with cancer have a higher incidence of venous thromboembolism (VTE).
      Little information currently exists on VTE and the understanding and beliefs of
      oncology nurses. Therefore, the attitudes and treatment practices of ambulatory
      oncology nurses were surveyed to determine the current knowledge base of VTE in
      patients with cancer. Survey results are presented along with a thorough
      literature review of thromboembolism and the unique risk factors for this
      frequent complication in patients with cancer. The causes of VTE in this patient
      population often are multifactorial and include hypercoagulability, stasis, and
      vascular endothelial damage from procedures or the neoplastic process itself. In
      particular, chemotherapy administration can increase the risk of thrombosis
      considerably. New therapies, including thalidomide, require oncology nurses
      caring for these patients to have heightened awareness of the potential for
      thrombogenic complications. This is the first of two articles that address the
      problem of thromboembolism in patients with cancer, including the survey results.
      (See part II on page 465.) Oncology nurses are essential in the care of VTE in
      patients with cancer and can help with patient identification, treatment, and
      compliance for improved patient outcomes.

PMID- 15515280
TI  - Venous thromboembolism in patients with cancer. Part II. Current treatment
      strategies.
AB  - Patients with cancer have an increased risk of thromboembolism. This complication
      is connected to a variety of different factors and is influenced by the
      conditions described in Virchow's triad: stasis, vascular endothelial damage, and
      hypercoagulability. Once thromboembolism is diagnosed, treatment in patients with
      cancer usually involves anticoagulation with unfractionated or low-molecular
      weight heparin and progression to oral anticoagulant therapy. Duration of
      treatment is usually three to six months, with most patients receiving six months
      of anticoagulation. Patients with cancer may be at risk for recurrent thrombosis
      as well, despite optimal use of oral anticoagulant therapy, and some of these
      patients may require lifelong heparin therapy. This article describes the current
      treatment regimens to provide anticoagulation therapy to patients with cancer,
      including a discussion of the low-molecular-weight heparins and dosing
      parameters. Nursing interventions to help provide these treatments safely are
      discussed. Patients with cancer have a high rate of thromboembolism; oncology
      nurses should heighten their awareness of this important complication, treatment
      options, and appropriate nursing interventions.

PMID- 15515281
TI  - Bortezomib, a newly approved proteasome inhibitor for the treatment of multiple
      myeloma: nursing implications.
AB  - Multiple myeloma (MM), a malignancy of the plasma cells, accounts for an
      estimated 14% of all newly diagnosed hematologic malignancies. Advances in
      chemotherapy and stem cell transplantation have improved survival rates, but MM
      remains incurable. Bortezomib (Velcade, Millennium Pharmaceuticals, Inc.,
      Cambridge, MA), a first-in-class proteasome inhibitor, has been approved for
      patients with MM who have received at least two prior treatments and have
      demonstrated disease progression on the most recent one. During clinical trials,
      most side effects were manageable with standard interventions. The most common
      toxicities were asthenic conditions (fatigue, malaise, and weakness),
      gastrointestinal disturbances (nausea, vomiting, diarrhea, and constipation),
      thrombocytopenia, peripheral neuropathy, pyrexia, and anemia. Supportive
      therapies and strategies for side-effect management can prevent worsening of
      these symptoms, thereby avoiding dose reductions and treatment delays. Oncology
      nurses play a key role in ensuring the proper and safe administration of
      bortezomib and often are the first to identify the signs of side effects. Patient
      education about anticipated side effects and close monitoring of patients can
      lead to symptom management interventions that are essential to patient comfort
      and safety.

PMID- 15515282
TI  - Evaluation of an educational tool to enhance outcomes for patients with head and
      neck cancer.
AB  - Patients with head and neck cancer often present with locally advanced disease at
      the time of diagnosis. Treatment plans include aggressive radiation therapy,
      often with concurrent chemotherapy. This treatment causes significant toxicity
      resulting from normal tissue damage. Currently, no consensus or evidence-based
      practice guidelines exist regarding which type of oral care products are best to
      use. Nurses in one radiation oncology department initiated a performance
      improvement project to develop oral care guidelines and an educational-tool for
      patients.

PMID- 15515283
TI  - Concurrent therapies that protect against doxorubicin-induced cardiomyopathy.
AB  - Doxorubicin is a chemotherapeutic agent successfully used in the treatment of a
      wide range of cancers. However, with cumulative doses, doxorubicin also is known
      to have cardiotoxic effects, including cardiomyopathy and heart failure. Research
      is targeted at maximizing the antitumor effects of doxorubicin while attenuating
      the potential cardiotoxicity. Concurrent therapies under study are combinations
      of doxorubicin with drugs such as probucol, carvedilol (Coreg, GlaxoSmithKline,
      Research Triangle Park, NC), dexrazoxane (Zinecard, Pfizer, New York, NY), and
      antioxidant nutrients. As patient advocates, nurses must be aware of current
      research, treatment options, and evidence-based patient resources and be diligent
      in assessing and educating patients before, during, and after treatment with
      doxorubicin.

PMID- 15515285
TI  - Chemotherapy-induced nail changes: an unsightly nuisance.

PMID- 15515284
TI  - Managing breakthrough pain: a clinical review with three case studies using oral
      transmucosal fentanyl citrate.
AB  - Pain management begins with the use of appropriate assessment tools and includes
      planning, implementing, and evaluating a comprehensive treatment plan that
      addresses persistent and breakthrough pain. Persistent pain is present to some
      degree throughout the day and primarily is controlled with around-the-clock
      medication. However, it often is accompanied by episodes of short, intermittent
      pain, also known as breakthrough pain. From a clinical perspective, breakthrough
      pain is characterized as a transitory exacerbation of pain that occurs on a
      background of otherwise stable pain in a patient receiving chronic opioid
      therapy. Breakthrough pain typically is moderate to severe in intensity and can
      be triggered by various activities (incident pain), be entirely unpredictable
      (idiopathic pain), or occur toward the end of around-the-clock medication (end-of
      dose failure). Breakthrough pain occurs in as many as 86% of patients with cancer
      even when persistent pain is well controlled. Clinicians and patients should
      address persistent and breakthrough pain as distinct entities to accurately
      assess it and develop appropriate pain management plans. This article provides an
      overview of the clinical characteristics of persistent and breakthrough pain and,
      through the use of three case studies, illustrates practical strategies for
      managing breakthrough pain effectively.

PMID- 15515286
TI  - Clinical trials in cancer. Part I. Biomedical, complementary, and alternative
      medicine: finding active trials and results of closed trials.
AB  - Most cancer CAM clinical trials are treatment or supportive care trials in phase
      I, II, or III status. A recent search showed that, at present, a very limited
      number of retrievable pharmaceutical- or industry-sponsored cancer CAM clinical
      trials is listed in publicly accessible databases. Two databases, Center Watch
      and Trial Check, focus on industry, healthcare providers, and patient advocate
      groups and have fees or limited access. As more clinical trials are imported from
      NLM's Clinical Trials.gov to NCI's PDQ database, more cancer CAM trials will be
      accessible and free to the public. Published results from clinical trials are
      available in multiple locations and retrievable with advanced searching but
      remain of limited access to most of the public because of academic or hospital
      library subscription services. All cancer clinical trial results are not likely
      to be housed in one location (either via database or in print); thus, cancer CAM
      clinical trial results likely will not be either. Because PDQ currently is the
      central location for cancer CAM clinical trial listings in the United States, the
      database should be expanded to include published results that are retrievable by
      healthcare professionals and the lay public free of charge. In clinical and
      research roles, oncology nurses are compelled to keep abreast of advances in
      cancer care, especially in the realm of cancer clinical trials. Keeping abreast
      of results of cancer CAM clinical trials is vital for oncology nurses in patient
      education, advocacy, and advancement of evidence-based practice.

PMID- 15515287
TI  - Colorectal cancer screening: a review of the evidence.

PMID- 15515288
TI  - Hematopoietic stem cell transplantation.

PMID- 15515289
TI  - It's a guy thing--or is it?

PMID- 15515290
TI  - Preparing for prescriptive privileges: a standard for the psychiatric-mental
      health preceptorship.
AB  - TOPIC: Establishing a standard for preparation for prescriptive authority for
      advanced practice psychiatric nurses. PURPOSE: To outline a best practice
      standard for the clinical and prescriptive authority preceptorship. SOURCES:
      NACNS and NONPF competencies and practice guidelines. CONCLUSIONS: The authors
      recommend a clinical preceptorship with planned faculty monitoring, clinical
      logs, case studies, and group supervision to prepare the psychiatric-mental
      health advanced practice nurse to serve within the expanded prescribing role.

PMID- 15515291
TI  - EMDR: implications of the use of reprocessing therapy in nursing practice.
AB  - TOPIC: Eye movement desensitization and reprocessing (EMDR). PURPOSE: To examine
      the available evidence base for EMDR treatment in psychiatric nursing practice.
      SOURCES: Evidenced-based research findings, published case and anecdotal reports,
      and primary source documents on the development of the treatment method.
      CONCLUSIONS: EMDR use remains controversial. Although it is safe, little is known
      regarding the mechanism of action of any therapeutic effect; more rigorous
      empirical establishment of efficacy is needed.

PMID- 15515292
TI  - Incorporating individual spiritual beliefs in treatment of inpatient mental
      health consumers.
AB  - PURPOSE: To promote incorporation of spiritual beliefs into inpatient crisis
      psychiatric care. SOURCES: Published literature, Web resources. CONCLUSIONS:
      Individual spiritual resources appear helpful to the consumer in times of crisis.
      Further identification of ways to apply spirituality, as well as professional
      standards, is still needed.

PMID- 15515293
TI  - Walking: an important therapeutic tool.

PMID- 15515294
TI  - Memantine: a new approach to Alzheimer's disease.

PMID- 15515295
TI  - Bipolar II or unipolar depression: pharmacologic considerations.

PMID- 15515296
TI  - Competences of qualified nurses in assisting the physician specialist in
      anesthesia: actual state of affairs from a legal point of view.

PMID- 15515297
TI  - The professional image anticipated by anaesthesiologists.
AB  - The perspective of anaesthesiologists regarding their professional image in the
      eyes of colleagues and the public was assessed. A self-reporting questionnaire
      (Instrument for Stress-related Job Analysis) was completed by 125
      anaesthesiologists. Respondents' self-image and presumed image in the eyes of
      colleagues do not give a bright picture of the anaesthesiologist's role. The
      anticipated image showed significantly more anaesthesiologists who presumed low
      professional recognition by their colleagues from other specialties (P = 0.002)
      and the lay public (P = 0.015) than those who assumed high marks. Presumed
      colleague opinion correlated significantly with characteristics of job
      satisfaction including the possibility to co-determine sequence of operations (P
      = 0.006), recognition of suggestions and ideas (P = 0.007) and fellow support (P
      = 0.001). Regarding working conditions the possibility to actively control
      operational procedures also significantly correlated with colleague opinion (P =
      0.003). The authors conclude that the possibility to actively influence quality
      and pace of work on a par with surgical colleagues could help boost self-esteem
      and self-confidence in anaesthesiologists. Furthermore, positive image promotion
      in cooperating medical professions and the public could help focus more attention
      on the important contribution of anaesthesiology to modern medicine.

PMID- 15515298
TI  - Cerebral oximetry in patients undergoing carotid endarterectomy: preliminary
      results.
AB  - Carotid endarterectomy (CEA) is an appropriate treatment for carotid occlusive
      disease. The risk of stroke during CEA ranges from 1.1% to 7.5%. Shunting is
      usually advised when severe ischemia during cross-clamping of the internal
      carotid artery is suspected. Routine use of an intraluminal shunt may increase
      the perioperative stroke rate. Popular and well documented methods of neurologic
      monitoring for ischemia during general anesthesia are electroencephalography
      (EEG) and transcranial Doppler ultrasonography (TCD) of the middle cerebral
      artery. The purpose of this prospective study was to compare cerebral oximetry
      using near infrared spectrophotometry (NIRS) with EEG and TCD. Preliminary data
      on 14 patients scheduled for elective carotid endarterectomy were included and a
      literature search was performed to correlate the findings. No postoperative
      neurologic events occurred. During carotid clamping there was a significant
      decrease in regional oxygen saturation (rSO2) but there was only a weak
      correlation with the decrease in mean Doppler flow (R = 0.74; P = 0.02) and no
      correlation with EEG changes (R = 0.49; P = 0.18). A useful rSO2 cut-off value
      predictive for cerebral ischemia could not be defined.

PMID- 15515299
TI  - Coronary sinus venoarterial CO2 difference in different hemodynamic states.
AB  - Myocardial metabolic rate and coronary flow are closely related limiting thus the
      diagnostic value of coronary sinus saturation monitoring as an indicator of flow.
      Regional venoarterial CO2 gradient was found elevated during low flow in various
      clinical and experimental conditions, in animals and humans. This study was
      undertaken to examine the impact of the variations of cardiac mechanical work on
      veno-arterial CO2 content and partial pressure difference (deltaPCO2) of the
      coronary sinus blood. Twenty-seven patients of either sex (m/f = 21/6),
      undergoing coronary artery bypass grafting under extracorporeal circulation, were
      studied. Monitoring included a Swan-Ganz catheter and a coronary sinus line. The
      correct position of the late was verified by the waveform displayed in the
      monitor. Immediately after cannulae placement, a hemodynamic profile was obtained
      and simultaneous arterial and coronary sinus sampling for blood gas analysis was
      done in an ABL 720 (Radiometer Copenhagen) analyzer. A second collection of the
      same data was obtained five minutes later with the patients in a slight "head
      down" position. Conditions for exclusion was intersample variation of
      hemoglobin's concentration greater than 15% and sodium ion concentration
      difference greater than 10% of the greater value. Arteriovenous oxygen partial
      pressure difference (deltaP(a-cs)O2), veno-arterial carbon dioxide partial
      pressure difference (deltaP(cs-a)CO2), O2 & CO2 content difference and heart's
      respiratory quotient were calculated and correlated to cardiac output (CO) and
      the other hemodynamic parameters. Statistical analysis employed t-paired test and
      linear regression. No ischemia was detected during sampling. "Head-down" position
      had a significant impact to all hemodynamic parameters except heart rate. In both
      data rows, although CO ranged widely and altered significantly, coronary sinus
      oxygen saturation and arteriovenous O2 content difference were stable and showed
      insignificant correlations to all the hemodynamic parameters that were studied.
      Carbon dioxide content difference (coronary sinus-arterial) showed a trending of
      decrease with higher flow. DeltaP(cs-a)CO2 appeared stable and independent of
      flow. Finally, respiratory quotient decreased significantly from 0.91 +/- 0.4 to
      0.86 +/- 0.4 (mean +/- SD; p < 0.05). The heart's high basal oxygen consumption
      and the almost near hemoglobin's desaturation transcoronary extraction of oxygen
      limits the value of coronary sinus saturation monitoring as indicator of coronary
      flow. Heart's little extraction reserve is faced with coronary flow reserve. In
      the physiologic range and under the conditions of anesthesia, elevated CO2
      production is accompanied with increased coronary flow. Under these
      circumstances, deltaP(cs-a)CO2 appears stable and is not suitable for clinical
      decisions concerning heart's coronary flow.

PMID- 15515300
TI  - Anaphylaxis during anaesthesia: diagnosis and treatment.
AB  - Anaphylactic and anaphylactoid reactions during anaesthesia are rare, but
      potentially life-threatening allergic events. The worst manifestations are
      cardiovascular collapse, bronchospasm and laryngeal oedema. Anaphylactic and
      anaphylactoid reactions are clinically indistinguishable. The most incriminated
      agents are neuromuscular blocking drugs and latex. Treatment consists of instant
      interruption of contact with possible antigens, 100% oxygen, intubation,
      adrenaline and volume expansion. The incidence of cross-reactivity between
      neuromuscular blocking drugs is high. Further investigation of a suspected
      anaphylactic reaction is mandatory to find the responsible drug and to make
      future anaesthesia safe. Diagnosis is made with intraoperative tests (serum
      histamine and mast cell tryptase) and postoperative tests (skin tests and RASTs
      for specific IgE antibodies).

PMID- 15515301
TI  - Remifentanil for foetal immobilisation and maternal sedation during endoscopic
      treatment of twin-to-twin transfusion syndrome : a preliminary dose-finding
      study.
AB  - Twin to twin transfusion syndrome (TTTS) affects 10 to 15% of monochorionic twin
      pregnancies. Untreated, perinatal loss exceeds 80%, of which survivors have a
      great risk for long-term neurological disorders as psychomotor retardation or
      cerebral palsy. TTTS can be treated using foetoscopy and selective ablation of
      the twin-to-twin blood vessels under local or regional anaesthesia. However,
      local or regional anaesthesia does not always result in excellent maternal
      comfort, nor does it provide foetal immobilisation, necessary for optimal
      surgical conditions. Using a continuous infusion rate of remifentanil 0.1
      microg/kg/min, perfect foetal immobilisation and excellent maternal sedation was
      achieved. Only mild respiratory acidosis was observed as a result of mild
      respiratory depression. In no mother apnoe occurred. All haemodynamic parameters,
      both foetal and maternal, remained stable during the procedure. Maternal
      sedation, respiratory depression and foetal immobilisation were quickly
      reversible following cessation of the remifentanil infusion.

PMID- 15515302
TI  - Postoperative residual curarisation: complication or malpractice?
AB  - Neuromuscular blocking drugs are often used in anaesthesia; in some types of
      surgery, their continuous infusion is indicated to limit the otherwise high
      incidence of movement. A large amount of postoperative residual curarisation is
      found after a single bolus, but more especially when continuous infusions are
      used in healthy patients and even more so in those with organ dysfunction or
      undergoing special types of surgery. Therefore, one should always optimise the
      dose requirements over time using neuromuscular transmission monitoring. Such
      monitoring should also help the clinician to antagonise selectively the
      neuromuscular block at the end of surgery. One should probably avoid routine
      antagonisation, especially in certain subgroups of patients, until a selective
      and safe reversal agent has been developed. At present, then, the only objective
      and reliable guide to facilitating the decision for selective antagonisation is
      the neuromuscular transmission monitor. Recent data and editorials warning about
      postoperative residual curarisation after boluses and infusions of neuromuscular
      blocking drugs have made residual curarisation one of the most feared
      complications in anaesthesia. There may be a consequent issue of malpractice if
      neuromuscular transmission monitoring is not used and/or pharmacological
      antagonisation is not performed.

PMID- 15515303
TI  - Intrathecal use of ropivacaine: a review.
AB  - Spinal anesthesia is a very old and popular anesthetic technique, with a high
      success rate and a good safety profile. In order to further improve and
      understand safety issues as well as the clinical use of spinal anesthesia, new
      local anesthetics and analgesic additives are being investigated for different
      applications. As practice of medicine focuses increasingly on outpatient care,
      spinal anesthetics should provide short-acting and adequate anesthesia without
      compromising early ambulation and discharge from the day surgery unit. A review
      of the current literature suggests that ropivacaine could have potential in this
      area.

PMID- 15515304
TI  - What comes after Bill 25? The challenge for nursing management.

PMID- 15515305
TI  - [Celine Goulet and a passion for learning. Interview by Nataly Rainville].

PMID- 15515307
TI  - [Road security and aging: how to prevent accidents].

PMID- 15515306
TI  - [Nursing practice in family medicine groups and its interdisciplinary context].
AB  - Nursing practice in family medicine groups (FMGs) is a major issue in the
      implementation of this new healthcare organization model in Quebec. Using a
      constructivist qualitative research approach, a case study of a FMG in a region
      of Quebec looked at how the partners involved in the project defined nursing
      practice, and highlighted the similarities and differences in their views. The
      results of this study show that nursing practice as a concept is perceived in two
      different ways: independent practice, associated with the recognition of nurses'
      potential, and interdisciplinary collaborative practice. Nurses view nursing
      practice from a client-base approach, whereas doctors view it from the
      perspective of how services are organized. The study found that trust is the
      fundamental element that makes interdisciplinary collaboration possible.

PMID- 15515308
TI  - [A better humanization of care: real possibility or utopia?].

PMID- 15515309
TI  - [A new initiative for the education of researchers].

PMID- 15515310
TI  - [Bacterial resistance: the new cold war].

PMID- 15515311
TI  - [The nurse and antibiotic resistance].

PMID- 15515312
TI  - [Analgesia and sedation in critical care. Nurses lead the protocol].

PMID- 15515313
TI  - [Analysis of the causes of enucleations performed at the Department of
      Ophthalmology of the Medical University of Lodz].
AB  - PURPOSE: To gather and analyse the data about causes of enucleations, which were
      performed in the Department of Ophthalmology, Medical University of Lodz.
      MATERIAL AND METHODS: The data were based on case histories. The whole examined
      group consisted of 57 patients, who had an enucleation surgery done in the period
      from June 1999 to June 2003. The analyzed data included: clinical diagnosis,
      visual acuity, intraocular pressure, results of histopathology examination and
      results of diagnostic imaging examinations. RESULTS: The most frequent causes of
      enucleations were: intraocular tumors (fraction 0.51 of the whole group), painful
      blind eyes (fraction 0.33), endophthalmitis (fraction 0.12) and ocular traumas
      (fraction 0.04). CONCLUSIONS: Despite significant advances in ophthalmology in
      recent years, enucleation remains a method of treatment. The main indications for
      this type of surgery are: intraocular tumors, painful blind eyes, severe
      endophthalmitis and some cases of ocular trauma.

PMID- 15515314
TI  - [Morphological parameters of the optic disc in patients with primary open angle
      glaucoma and low myopia].
AB  - PURPOSE: To compare the morphological parameters of the optic disc in patients
      with low myopia and primary open angle glaucoma (POAG) and in patients with
      glaucoma without refractive errors. MATERIAL AND METHODS: 53 patients, aged 33-88
      (56.2 +/- 11.9) with POAG were qualified for our study. The group was divided
      into two: first group consisted of 14 patients--11 women and 3 men, aged 41-83
      (58.2 +/- 10.9) comprising 28 eye balls with low myopia (-0.5 Dsph to -3.5 Dsph)
      and POAG. The second group consisted of 38 patients: 24 women and 14 men, aged 33
      80 (51.0 +/- 13.4) comprising 71 eye balls including 43 emetropic eyes, 26 eyes
      with hyperopia (+0.5 Dsph to +3.0 Dsph) and 2 eyes with astigmatism. All patients
      demonstrated early changes in visual field 1-2 stage due to the Aulhom
      classification. The measurements of the morphological parameters of the optic
      disc were made with confocal scanning laser ophthalmoscopy using Heidelberg
      Retina Tomograph--HRT II with glaucoma software. We analyzed the following
      parameters: optic disc area, cup area, rim area, cup/disc ratio, linear c/d
      ratio, mean cup depth, maximum cup depth. The statistical analysis was made using
      Kolomogarow-Smirnow test. RESULTS: All analyzed parameters were higher in
      patients with low myopia and POAG than in patients with only POAG. The results in
      both groups were different but still no statistically significant. CONCLUSIONS:
      Low myopia has an influence on the optic disc morphology in patients with POAG.

PMID- 15515315
TI  - [Confocal laser scanning tomography (HRT) in diagnosis and monitoring
      glaucomatous optic nerve damage in primary open angle glaucoma].
AB  - PURPOSE: The aim of this study was to estimate HRT usefulness in quantitative
      evaluation of structural glaucomatous optic nerve head damage and in monitoring
      this atrophy in POAG patients and normal subjects, during 18-monthly follow up.
      MATERIAL AND METHODS: 130 eyes of 84 patients with primary open angle glaucoma,
      52 women (79 eyes) and 32 men (51 eyes) in age 45-70 (mean = 54.69 yrs) and 96
      eyes of 48 normal subjects, 33 women (66 eyes) and 15 men (30 eyes) in age 40-70
      (mean=51.90 yrs). The ONH-stereometric parameters were examined using confocal
      laser scanning tomography--HRT (version 2.01). RESULTS: All of ONH stereometric
      parameters (except: HVC) statistically significant distinguish glaucoma and
      normal eyes. The most marked of ONH-parameters are: C/D area ratio, CA, CSM, RA,
      RV, Mean cup depth, CV, Max cup depth, Mean RNFL thickness, RNFL-csa and DA.
      Statistically significant changes of all ONH stereometric parameters in primary
      open angle glaucoma were found during follow up (except: HVC, CV and CSM).
      CONCLUSIONS: HRT is precise method for ONH-parameters evaluation. All of ONH
      stereometric parameters (except HVC) are good markers of quantitative ONH
      glaucomatous damage. HRT is valuable and precise method of quantitative
      monitoring progression of glaucomatous neuropathy.

PMID- 15515316
TI  - [Effect of pentoxifylline on Doppler blood flow parameters in the central retinal
      artery and the short posterior ciliary arteries in adolescents with progressive
      myopia].
AB  - PURPOSE: To evaluate the effect of pentoxifylline on blood flow in the central
      retinal artery and the short posterior ciliary arteries in patients with
      progressive myopia. MATERIAL AND METHODS: 48 eyes of 24 healthy patients aged
      between 12 and 18 years (mean 15.1 years) with myopia from -5.0 to -12.75 Dsph
      (mean -7.56 Dsph), were examined using color Doppler ultrasonography. The
      examination was performed before and after 10 days of intravenous administration
      of 200 mg of pentoxifylline. The peak-systolic, end-diastolic flow velocities,
      pulsatility, resistance and systolic/diastolic ratios were measured. RESULTS: The
      use of pentoxifylline significantly increased PSV and EDV in the central retinal
      artery and in the short posterior ciliary arteries (p=0.0001) in patients with
      progressive myopia and in the same time decreased PI, RI and S/D (p=0.0001).
      There was no correlation between Doppler blood flow parameters and dioptres or
      axial length. CONCLUSIONS: pentoxifylline increases retinal and choroidal blood
      flow in young patients with progressive myopia.

PMID- 15515317
TI  - [The estimation of macular hole surgery results].
AB  - PURPOSE: The purpose of the study was to estimate the results of macular hole
      surgery. MATERIAL AND METHODS: The data contains 57 patients (61 eyes) with stage
      3 or 4 macular holes who underwent three port pars plana vitrectomy, ILM peeling
      and gas endotamponade. Patients were divided into two groups: I group relates to
      38 operations conducted without a dye, II group contains 23 eyes which underwent
      macular surgery with a dye--trypan blue. RESULTS: The anatomical success rate
      after one surgery was 80.7% (47 eyes) and 89.5% (53 eyes) after additional
      vitrectomy [79% (30 eyes) in group I and 100% (23 eyes) in group II]. The
      functional improvement was observed in 55.3% (21 eyes) in group I and 74% (17
      eyes) in group II. Complications after operations included: retinal detachment,
      the increase of intraocular pressure and lens opacifications increase.
      CONCLUSIONS: Pars plana vitrectomy with ILM peeling is a successfully surgery
      procedure for macular holes. Trypan blue increases the safety and precision of
      surgery and improves the postoperative results.

PMID- 15515318
TI  - [Partial coherent interferometry--an alternative method for intraocular lens
      power calculation performed by ultrasonography].
AB  - PURPOSE: To compare axial length estimated by means of Zeiss IOLMaster and A-scan
      ultrasonography and anticipate postoperative refraction after IOL implantation
      with refraction measured after operation. MATERIAL AND METHODS: 26 patients were
      analyzed. Measurement of axial length was performed by Zeiss IOLMaster and A-scan
      ultrasonography. Preoperative refraction was determined by both methods based on
      SRK/T calculation formula and 119.0 and 120.5 A-constant for IOL. Postoperative
      refraction was expressed as a spherical equivalent and was obtained by
      autokeratorefraktometry in the first day after cataract surgery. RESULTS: Mean
      axial length measured by IOLMaster was longer by 0.06 mm in compared to
      ultrasound estimation (p < 0.001). The correlation between pre-operative
      refraction values determined by IOLMaster and post-operative measurements was
      statistically significant (p = 0.03). CONCLUSIONS: Measurement of axial length
      performed by IOLMaster is longer than by ultrasonography. IOLMaster seems to be
      more reliable method than ultrasonography in intraocular artificial lens
      calculation in cataract surgery.

PMID- 15515319
TI  - [Endogenous uveitis during pregnancy--a report of 4 cases].
AB  - PURPOSE: To estimate the influence of pregnancy on the clinical course of
      endogenous uveitis. MATERIAL AND METHODS: Four pregnant women (6 eyes) aged 16-21
      yrs with uveitis of unknown etiology were observed. In two cases uveitis was
      bilateral while other two patients developed unilateral intraocular inflammation.
      At the time when the pregnancy was diagnosed systemic steroids were discontinued.
      Ophthalmic examination was performed every 1-2 months and then 3-8 months after
      delivery. RESULTS: In all cases, before pregnancy, the active stage of uveitis
      was observed; vitreous flare and vitreous cells were present in all cases (6
      eyes). Iritis was present in one patient (1 eye), inflammatory chorioretinal
      lesions in 2 cases (3 eyes), while retinal vasculitis was observed in one case (1
      eye). During pregnancy as well as within 3-8 months of follow-up after delivery,
      neither progression nor recurrences of uveitis were observed. In all patients
      gradual, total regression of intraocular inflammation with the improvement of
      visual acuity in 3 cases were noted. CONCLUSIONS: Our observations can suggest
      positive influence of pregnancy on uveitis activity.

PMID- 15515320
TI  - [Alport's syndrome--case report].
AB  - The history and clinical findings of 30-year man with Alport's syndrome are
      presented. The main features of Alport's syndrome are hereditary chronic
      nephritis leading to renal failure resulting in death and sensory-neural
      deafness. Ocular features include anterior lenticonus, macular and peripheral
      flecks resembling fundus albipunctatus. The etiology of this syndrome is unknown.
      It has been suggested that there may be a metabolic defect in the biosynthesis of
      collagen with changes in the glomerular basement membrane, cochlea and capsule of
      the lens. The retinal flecks may also be related to the different underlying
      glial cells, Mullers cells producing thick basement membrane. It is concluded
      that diagnosis of fundus albipunctatus should not be made in the absence of full
      renal investigation and audiometry.

PMID- 15515321
TI  - [Central serous choroidopathy in a 57 years old woman].
AB  - A 57 years old patient with unilateral decrease of vision with accompanying
      micropsia and metamorphopsia is presented. After ophthalmological examination,
      fluorescein angiography and ultrasound examination we diagnosed idiopathic
      central serous choroidopathy. After photocoagulation the improvement of visual
      acuity was achieved.

PMID- 15515322
TI  - [Mycotic lacrimal canaliculitis--cases report].
AB  - Mycotic lacrimal canaliculitis is a rare eye disease. Overuse of antibiotics and
      steroids in the treatment of eye infections is a very serious risk factor.
      Initial diagnosis of the mycotic infection may be difficult, thus infection may
      lasts for months. Chronic conjunctivitis, itching, burning sensations, poor
      response to the treatment may suggest a suspicion of the mycosis. In our paper we
      report two cases of the mycotic lacrimal canaliculitis, diagnosis and treatment.
      We could not culture fungal colonies, but we have found fungal structures in
      direct microscopic detection during the examination of deposits found in the
      canaliculi. In our opinion it is important to consider fungal infections during
      the treatment of chronic eye disorders.

PMID- 15515323
TI  - [Diagnostic problems of unilateral exophthalmos--case report].
AB  - This paper presents a case of a 54-year-old patient with unilateral exophthalmos.
      During the hospitalization basic laboratory investigations, USG, skull X-ray
      film, NMR of orbits were carried out. The patient was treated with systemic
      corticosteroids with good response. Inflammatory infiltration and venous stasis
      are considered to be the cause of exophthalmos. Granulomatous orbital
      inflammation was detected. The etiology of nonspecific orbital inflammation
      remains still unknown.

PMID- 15515324
TI  - [Localization and clinical characteristics of the ocular metastases of solid
      extraocular tumours].
AB  - Localization and clinical characteristics of the ocular metastases of solid
      tumours are presented. Choroid is the most common localization site of these
      metastases, however they may involve each ocular structure. In the most cases
      they are diagnosed in patients with earlier recognized cancer, but in 12-40% of
      the patients ocular metastasis is a first sign of the neoplasm. Therapy is
      focused to save the eye function or last but not least to improve patient's
      status.

PMID- 15515325
TI  - [Theoretical and clinical aspects of the use of prostaglandins in glaucoma
      therapy].
AB  - In the first part of the article the main information and recent research on the
      uveoscleral outflow pathway, including its morphology and physiology were
      presented. The structure of extracellular matrix of ciliary muscle and the
      changes of it, that are induced by prostaglandins, resulting in decreasing
      intraocular pressure were emphasized. In the second part biochemical
      characteristics of prostaglandin analogues, using nowadays were presented. Their
      efficacy in reducing intraocular pressure and safety profile were described.

PMID- 15515326
TI  - [Chosen etiopathogenetic factors in formation and development of retinopathy of
      prematurity (ROP)].
AB  - Retinopathy of prematurity remains a serious problem in newborns. Sometimes
      despite of better ophthalmologic control and knowledge of pathomechanism of ROP,
      there is no possibility to avoid blindness. Today attention is concentrated on
      searching in pathophysiology, immunology and other branches of medical sciences
      to explain the nature of disease. The aim of this article is to analyze some
      factors which play an important role in development of ROP.

PMID- 15515327
TI  - [Multifocal electroretinogram].
AB  - The paper presents current state of knowledge regarding multifocal
      electroretinography (mfERG). The theoretical basis of this technique, procedure,
      methods and examples of use in clinical diagnostics are presented.

PMID- 15515328
TI  - [Visual system involvement in selected zoonotic diseases. II. Trichinellosis].
AB  - Trichinellosis is the medical problem that is still actual in our country. The
      paper presents recent taxonomic data regarding Trichinella spp. as well as
      selected epidemiologic aspects. Pathomechanism of trichinellosis and the outline
      of clinical pathology are also discussed. The image of lesions involving organ of
      sight, diagnostic methods and treatment are described with details as well. The
      paper is highlighting the role of ophthalmologist in early diagnosis of
      trichinellosis.

PMID- 15515329
TI  - [Ophthalmic aspects in Celsus' work De medicina libri octo].
AB  - The article presents Aulus Cornelius Celsus (living in Roman Empire 15 BC - 50
      AD) and his famous work "De medicina libri octo", one of the main sources of
      knowledge on the ancient medicine. It briefly goes through the content of the
      medical treaties. A wider discussion of the following ophthalmic aspects,
      included in Book VI and Book VII, is provided: the anatomy of the eye, the
      description of ophthalmic diseases, methods of its preventive treatment and
      surgery. It is also mentioned that the work contains the first description of
      cataract surgery (couching method) in the medical literature. The article
      underlines the popularity enjoyed by Celsus' work in medieval Europe.

PMID- 15515331
TI  - Periodontal changes in patients undergoing radiotherapy.
AB  - BACKGROUND: The purpose of this study was to evaluate changes in the periodontium
      in patients who received head and neck radiation therapy. METHODS: Periodontal
      clinical parameters (probing depth, clinical attachment level, gingival
      recession, plaque index, and bleeding on probing) were assessed on 27 patients
      before and 6 to 8 months following radiation therapy in the head and neck area.
      RESULTS: The greatest changes occurred in clinical attachment level: overall,
      70.3% of the patients showed a loss, with 92% evincing loss in the mandible.
      Attachment loss was directly related to the field of radiation and was greater
      when the jaws were actually included in the irradiated area. CONCLUSION:
      Periodontal status should be evaluated prior to and following radiation therapy
      in the oral-maxillary-facial region to help ensure that periodontal health is
      maintained in oncology patients.

PMID- 15515332
TI  - A randomized clinical trial comparing enamel matrix derivative and membrane
      treatment of buccal class II furcation involvement in mandibular molars. Part II:
      secondary outcomes.
AB  - BACKGROUND: This multicenter, randomized trial compared enamel matrix derivative
      (EMD) with barrier membranes for the treatment of Class II mandibular furcations
      with regard to secondary outcomes. The influence of furcation morphology on the
      effectiveness of either treatment was also evaluated. METHODS: Forty-eight
      patients (age range 28 to 73 years; 22 females, 26 males) with buccal Class II
      furcation involvements in both contralateral lower first or second molars were
      included. After initial periodontal treatment, defects were randomized to either
      EMD or bioabsorbable guided tissue regeneration (GTR) barrier. Study design and
      the results for the primary parameter were previously described. Results of the
      following secondary outcome variables are reported here: changes of the hard
      tissue boundaries describing the anatomical situation of the furcation defect and
      changes in the following clinical parameters between baseline and 14 months:
      plaque, level of gingival margin, probing depth, bleeding on probing, attachment
      level, and bone sounding at five sites/tooth at the buccal side. Descriptive
      statistics were applied for changes in clinical parameters and measurements of
      hard tissue boundaries. The differences observed under treatment with EMD or
      membrane were analyzed by means of the Wilcoxon two-sample test. The difference
      between the effect of the EMD and membrane treatment was estimated by means of
      the Hodges-Lehmann estimator. RESULTS: Overall, similar healing results were
      observed for both treatments. However, there was slightly more recession in the
      mid-furcation site following membrane treatment (P = 0.04). Additionally,
      different treatment effects could be detected for the distances from the stent or
      cemento-enamel junction (CEJ) to the buccal bone crest, mid-distal root (Pstent =
      0.01; PCEJ = 0.07) and for the distance from the stent or CEJ to the buccal bone
      crest, mid-mesial root (Pstent = 0.01; PCEJ = 0.01). There was no measurable bone
      resorption in EMD sites, whereas a slight resorption occurred with membrane
      treatment. Furcation morphology at the time of surgery was not associated with
      clinical outcome, irrespective of the treatment. CONCLUSION: With regard to
      secondary outcome parameters, enamel matrix derivative treatment led to a similar
      regenerative result as the membrane procedure.

PMID- 15515333
TI  - Alendronate may protect against increased periodontitis-related bone loss in
      estrogen-deficient rats.
AB  - BACKGROUND: The aim of this study was to evaluate the impact of alendronate (ALD)
      and estrogen (EST) therapies and their withdrawal on bone loss in experimental
      periodontitis in ovariectomized rats. METHODS: Eighty-seven Wistar rats were
      divided into six groups: group 1 (N = 15): sham surgery; group 2 (N = 15):
      ovariectomy (OVX); group 3 (N = 15): OVX plus alendronate administration for 80
      days (AT); group 4 (N = 14): OVX plus alendronate administration for 40 days
      (AW); group 5 (N = 14): OVX plus 17beta estradiol administration for 80 days
      (ET); and group 6 (N = 14): OVX plus 17beta estradiol administration for 40 days
      (EW). Twenty-one days after ovariectomy or sham surgery, one mandibular molar was
      randomly assigned to receive a ligature, while the contralateral tooth was left
      unligated. Sixty days later, the animals were sacrificed and the specimens
      processed. RESULTS: OVX presented a direct impact on alveolar bone, regardless of
      plaque accumulation and significantly increased bone loss resulting from
      periodontitis (P < 0.05). The effect of OVX on unligated sites was significantly
      reduced by AT, AW, and ET (P < 0.05), but not by EW (P > 0.05). In addition,
      alendronate administration (AT/AW) significantly reduced the impact of OVX on
      periodontitis-related bone loss (P < 0.05), while estradiol did not (P > 0.05).
      CONCLUSION: Within the limits of this study, alendronate administration, but not
      estrogen replacement, may protect against the impact of estrogen deficiency on
      alveolar bone presenting a significant residual effect after its withdrawal.

PMID- 15515334
TI  - Gingival crevicular fluid levels of interleukin-1beta and glycemic control in
      patients with chronic periodontitis and type 2 diabetes.
AB  - BACKGROUND: Patients with diabetes have increased incidence and severity of
      periodontal disease not accounted for by differences in the subgingival microbial
      infection. Poor glycemic control has been consistently associated with
      periodontal disease severity. Also, recent evidence suggests that hyperglycemia
      may induce inflammatory cytokine production. Few studies, however, have examined
      local biochemical measures of periodontal inflammation in patients with type 2
      diabetes. The aim of this study was to determine whether glycemic control was
      related to gingival crevicular fluid (GCF) levels of interleukin-1beta (IL
      1beta). METHODS: GCF samples were collected from 45 patients with type 2 diabetes
      and untreated chronic periodontitis. Plaque index (PI), bleeding on probing
      (BOP), probing depth (PD), and attachment level (AL) were recorded at six sites
      per tooth. IL-1beta levels were determined from individual GCF samples by enzyme
      linked immunoabsorbent assay (ELISA). Individual site and mean patient values
      were calculated. Glycated hemoglobin (HbA1c) levels were measured from
      anticoagulated whole blood using an automated affinity chromatography system.
      Serum glucose was also determined. RESULTS: Clinical periodontal measures (PD,
      AL, BOP) and measures of glycemic control (HbA1c, random glucose) were
      significantly correlated with GCF IL-1beta. Patients with greater than 8% HbA1c
      had significantly higher mean GCF IL-1beta levels than patients with less than 8%
      HbA1c. In a multivariate model adjusting for age, gender, PD, AL, BOP, and PI,
      HbA1c and random glucose were independent predictors of high GCF IL-1beta.
      CONCLUSIONS: Poor glycemic control is associated with elevated GCF IL-1beta.
      These data are consistent with the hypothesis that hyperglycemia contributes to
      an heightened inflammatory response, and suggests a mechanism to account for the
      association between poor glycemic control and periodontal destruction.

PMID- 15515335
TI  - Relative proportions of T-cell subpopulations and cytokines that mediate and
      regulate the adaptive immune response in patients with aggressive periodontitis.
AB  - BACKGROUND: Both the virulence factors of periodontopathic bacteria and the
      immune response against them have been involved in tissue destruction observed in
      periodontal disease. Considering the regulatory role of cytokines produced by T
      cells, the purpose of this study was to compare the CD3+, CD4+, and CD8+
      subpopulations of T cells, and to characterize the mRNA of cytokines involved in
      the adaptive immune response in a group of healthy/gingivitis 1 (HI/G1)
      individuals and aggressive periodontitis (AgP) patients. METHODS: The percentages
      of T-cell subpopulations were analyzed in 10 gingival samples of HI/G1
      individuals and 10 gingival samples of AgP patients by immunohistochemistry. The
      presence of interleukin (IL)-2, interferon (IFN)-gamma, IL-4, IL-5, IL-10, IL-
      13, and transforming growth factor (TGF)-beta was measured by reverse
      transcription polymerase chain reaction (RT-PCR) of mRNA extracted from complete
      gingival biopsies. RESULTS: Significant differences were found in CD3+ and CD4+
      cell counts between both groups. The parameters were lower in the gingival
      biopsies from AgP patients while CD8+ counts were similar in both groups. The
      cytokine mRNA analysis showed constant expression of IL-2 and IFN-gamma in all
      cases. The mRNA of IL-5 and IL-10 was present in the majority of HI/G1 (N = 10, N
      = 9, respectively) but was not in the AgP group (N = 2, N = 1). IL-13 and TGF
      beta were only detected in HI/G1 (N = 2, N = 3) and IL-4 was not detected in any
      of the individuals. CONCLUSIONS: These results indicate that the role of the CD8+
      subpopulation in aggressive periodontitis lesions is limited. On the other hand,
      cytokines IL-2 and IFN-gamma may not be relevant in the progression of aggressive
      periodontitis.

PMID- 15515336
TI  - TT virus infection of periodontal tissues: a controlled clinical and laboratory
      pilot study.
AB  - BACKGROUND: A novel single-strand, circular DNA virus has been recently isolated
      and named TT virus (TTV). It has been demonstrated that peripheral blood cells
      harbor TTV DNA, suggesting that the virus might replicate in lymphoid cells and
      contribute to lymphocyte imbalances with consequent immunosuppressive effects.
      The purpose of this study was to investigate the prevalence of TTV DNA in healthy
      and periodontally compromised subjects, evaluating the presence of the virus in
      the gingiva and saliva, and comparing virological results with clinical data.
      METHODS: Twenty-one patients (seven males and 14 females, aged 25 to 76 years)
      were enrolled in the study. Eleven subjects were diagnosed with moderate
      periodontitis, while 10 were periodontally healthy. A sample of saliva was taken
      from each patient before recording the periodontal data; subsequently, a gingival
      biopsy was performed. A real-time polymerase chain reaction was used to quantify
      the presence of TTV DNA in saliva and gingival specimens. RESULTS: A
      statistically significant association was found between TTV in gingival tissue
      and the presence of periodontitis (P = 0.0351), while no association was observed
      between TTV in saliva and the presence of periodontitis (P = 0.4762).
      CONCLUSIONS: A new DNA virus (TTV) was first identified in the gingival tissue
      and was found to be significantly associated with the presence of periodontitis.
      These findings need to be investigated in further studies.

PMID- 15515337
TI  - Influence of parameters on root surface roughness following treatment with a
      magnetostrictive ultrasonic scaler: an in vitro study.
AB  - BACKGROUND: This in vitro study aimed to evaluate the influence of different
      parameters, i.e., lateral force, instrument power setting, and the shape of the
      working tip, on the roughness of root surfaces following treatment with a
      magnetostrictive ultrasonic scaling device. METHODS: The study sample comprised a
      total of 102 extracted human molars, premolars, canines, and incisors. The
      samples were randomly divided into 10 equal units of 10 each for treatment with
      the ultrasonic device at a lateral force of 0.5 N and 2.0 N, a low and high
      instrument power setting, and with a straight and angulated shaped working tip.
      Twenty samples were treated manually using curets at a lateral force of 0.5 N and
      2.0 N. Two samples were left untreated as controls. The mean (Ra) and maximum
      (Rmax) surface roughness of each sample was recorded. The statistical analysis
      was performed using analysis of variance (three-way ANOVA) at a level of
      significance of 5% (P < 0.05). RESULTS: The mean surface roughness (+/-SD) using
      different parameters ranged from 0.6 +/- 0.1 microm to 1.8 +/- 0.3 microm. The
      maximum surface roughness (+/-SD) was between 4.8 +/- 1.3 microm and 17.2 +/- 4.3
      microm. The mean surface roughness (+/-SD) for samples treated with curets at a
      lateral force of 0.5 N was 0.5 +/- 0.0 microm and 0.4 +/- 0.1 microm at 2.0 N.
      The maximum surface roughness (+/-SD) was 3.7 +/- 0.8 microm at 0.5 N and 3.9 +/-
      1.4 microm at 2.0 N. CONCLUSIONS: The findings of the present study indicate that
      the shape of the working tip and the lateral force significantly influence the
      mean and maximum surface roughness of root surfaces treated with a
      magnetostrictive ultrasonic scaling device. At any specific parameter, the
      surface roughness was significantly higher for the ultrasonic scaling device as
      compared to the hand curet.

PMID- 15515338
TI  - Locally applied isosorbide decreases bone resorption in experimental
      periodontitis in rats.
AB  - BACKGROUND: The role of nitric oxide (NO) on bone metabolism is controversial,
      since it can either stimulate bone formation or resorption. We investigated the
      effect of local administration of the NO donor isosorbide in an experimental
      periodontal disease model. METHODS: Wistar rats were subjected to a ligature
      placement around the cervix of the right second upper molar and were sacrificed
      after 11 days. Alveolar bone loss was measured in one quadrant as the sum of the
      distances between the cuspid tip and the alveolar bone along the axis of each
      molar root, which was subtracted from the contralateral side, used as unligated
      control. The semiquantitative histopathological scale of the periodontium was
      based on cell infiltration and alveolar bone and cementum integrity. Groups were
      treated with a gel containing 1% or 5% isosorbide applied to the vestibular side
      of the molar gingiva 1 hour before the placement of the ligature and then twice
      daily until sacrifice. Controls included one group subjected to periodontitis and
      no treatment (NT) and another that received the gel containing just the vehicle
      (V). RESULTS: The application of the vehicle gel produced an increase of the
      alveolar bone resorption, without altering the inflammatory changes, compared to
      the NT group. The 5% isosorbide produced a significant reduction of the alveolar
      bone resorption, compared to V and NT. This reduction was confirmed by
      histological analysis, showing less inflammatory cell infiltration and
      preservation of the cementum and the alveolar process. CONCLUSION: Local
      application of isosorbide reduces alveolar bone resorption in experimental
      periodontal disease in rats, suggesting a local anti-inflammatory effect of
      isosorbide.

PMID- 15515339
TI  - Effects of implant thread geometry on percentage of osseointegration and
      resistance to reverse torque in the tibia of rabbits.
AB  - BACKGROUND: Dental implant thread geometry has been proposed as a potential
      factor affecting implant stability and the percentage of osseointegration.
      Therefore, the aim of this prospective, randomized, parallel arm study was to
      evaluate the effects of dental implant thread design on the quality and percent
      of osseointegration and resistance to reverse torque in the tibia of rabbits.
      METHODS: Seventy-two custom-made, screw-shaped, commercially pure titanium
      implants (3.25 mm diameter x 7 mm length) were placed in the tibiae of 12 white
      New Zealand rabbits. Each tibia received three implants of varying thread shapes:
      one with a V-shaped, one with a reverse buttress, and one with a square thread
      design. The rabbits were sacrificed following an uneventful healing period of 12
      weeks. Implants in the right tibiae underwent histologic and histomorphometric
      assessments of the bone-to-implant contact (BIC) and the radiographic density of
      surrounding bone, while implants in the left tibiae were used for reverse-torque
      testing. Differences between the three thread designs were examined using
      analysis of variance (ANOVA). RESULTS: Data showed that the square thread design
      implants had significantly more BIC and greater reverse-torque measurements
      compared to the V-shaped and reverse buttress thread designs, while no
      differences were found in radiographic bone density assessments. CONCLUSION:
      These results indicate that the square thread design may be more effective for
      use in endosseous dental implant systems.

PMID- 15515340
TI  - Effect of the vertical and horizontal distances between adjacent implants and
      between a tooth and an implant on the incidence of interproximal papilla.
AB  - BACKGROUND: The interproximal dental papilla is considered an essential component
      of the anterior and posterior regions of the maxilla and mandible. The absence of
      this structure has esthetic and phonetical consequences and lateral food
      impaction problems occur with the implant-supported prosthesis. The aims of the
      present study were to: 1) evaluate the effect of the vertical and horizontal
      distances between adjacent implants (group 1) and between a tooth and an implant
      (group 2) on the presence of the interproximal dental papilla; and 2) determine
      whether the interaction between the vertical and horizontal distances might be
      associated with the incidence of the papilla. METHODS: In 48 patients, 96
      interproximal sites in group 1 and 80 in group 2 were examined. The distance from
      the base of the contact point to the bone crest (D1), the distance between tooth
      and implant or between two implants (D2), and the distance from the base of the
      contact point to the tip of the papilla (D3) were measured. RESULTS: In both
      groups, when D2 was 3, 3.5, or 4 mm, the papilla was present most of the time (P
      < 0.05), and when D2 was 2 or 2.5 mm, the papilla was absent 100% of the time (P
      < 0.05). Further, in group 2, when D1 was between 3 and 5 mm, the papilla was
      present most of the time (P < 0.05). However, in Group 1, only when D1 was 3.0 mm
      was the papilla present most of the time (P < 0.05). For both groups, analysis of
      the interaction between D1 and D2 showed that when D2 was < or = 2.5 mm, the
      papilla was absent; otherwise, when D2 was > or = 3 mm, there was an interaction
      between D1 and D2. CONCLUSIONS: We conclude that the ideal distance from the base
      of the contact point to the bone crest between adjacent implants is 3 mm and,
      between a tooth and an implant, 3 mm to 5 mm. The ideal lateral spacing between
      implants and between tooth and implant is 3 mm to 4 mm. Further, there is an
      interaction between horizontal and vertical distances when the lateral spacing is
      greater than 3 mm.

PMID- 15515341
TI  - The role of parathyroid hormone-related protein in the regulation of
      osteoclastogenesis by cementoblasts.
AB  - BACKGROUND: Parathyroid hormone-related protein (PTHrP) promotes
      osteoclastogenesis by inhibiting expression of osteoprotegerin (OPG), a decoy
      receptor for the receptor activator of nuclear factor kappa B (RANK), and by
      enhancing production of RANK ligand (RANKL) by osteoblasts. However, little is
      known regarding the role of PTHrP in regulating cementoblast-mediated
      osteoclastogenesis. METHODS: This study determined the impact of PTHrP on
      osteoclastogenesis using: 1) OCCM-30 (immortalized murine cementoblasts), 2) RAW
      264.7 cells (murine myeloid cells), or 3) OCCM-30 plus RAW 264.7 cells. Cells
      were treated with PTHrP (1-34), RANKL, or PTHrP and RANKL combined. Enzyme-linked
      immunosorbent assays (ELISAs) for OPG and RANKL were performed on media and cell
      lysates, and tartrate-resistant acid phosphatase (TRAP) and mRNA detection for
      the osteoclast associated receptor (OSCAR) were performed. RESULTS: The highest
      numbers of TRAP-positive cells and cells expressing OSCAR were found in the RAW
      cell group treated with either RANKL alone or RANKL and PTHrP. TRAP-positive
      cells were fewer when OCCM cells were co-cultured with RAW, but the greatest
      numbers were still with both PTHrP and RANKL. OPG levels were highest from OCCM
      cells and PTHrP decreased these levels. In contrast, RANKL levels were low in
      OCCM cell lysates and PTHrP increased RANKL. In vivo studies also revealed high
      osteoclastic activity surrounding developing teeth in mice administered PTH.
      CONCLUSIONS: These results demonstrate that PTHrP influences the balance of OPG
      and RANKL production by cementoblasts, and further indicate that this effect, in
      the context of surrounding cells, might have a significant impact on
      osteoclastogenesis, root resorption, and tooth eruption.

PMID- 15515342
TI  - Platelet-released supernatant increases matrix metalloproteinase-2 production,
      migration, proliferation, and tube formation of human umbilical vascular
      endothelial cells.
AB  - BACKGROUND: Local application of platelets represents a promising tool to enhance
      bone regeneration. New bone formation strictly requires blood vessel formation, a
      sequential process involving matrix degradation, migration, proliferation, and
      tube formation of endothelial cells. Here we investigated the impact of secreted
      granula products from activated platelets on endothelial cells, and determined
      the involvement of extracellular signal-regulated kinase (ERK) signaling.
      METHODS: The effects of platelet-released supernatant on endothelial cells were
      investigated using in vitro models. Matrix metalloproteinase-2 (MMP-2) release,
      migration, proliferation, and tube formation of human umbilical vascular
      endothelial cells (HUVEC) were determined in response to platelet-released
      supernatant by gelatine zymography, Boyden chamber assay, 3[H]thymidine
      incorporation, and basement membrane assay, respectively. All experiments were
      performed in the presence of the ERK signaling inhibitor PD98059. ERK
      phosphorylation was detected by Western blot analysis. RESULTS: Incubation with
      platelet-released supernatant increased the production of MMP-2, migration,
      proliferation, and tube formation of HUVEC. Platelet-released supernatant also
      stimulated ERK phosphorylation in HUVEC. Inhibition of ERK signaling decreased
      platelet-released supernatant-stimulated endothelial cell proliferation, but not
      MMP-2 activity, migration, and the formation of capillary tubes. CONCLUSIONS: Our
      data suggest that secreted granula products from platelets can enhance different
      stages of blood vessel formation, and that ERK signaling is required to mediate
      the mitogenic effects of the supernatant. These findings support the hypothesis
      of a potential link between platelet activation and blood vessel formation during
      bone regeneration.

PMID- 15515343
TI  - Loaded custom-made zirconia and titanium implants show similar osseointegration:
      an animal experiment.
AB  - BACKGROUND: Zirconia might be an alternative material to titanium for dental
      implant fabrication. The aim of the present study was to investigate the
      histological behavior (osseointegration) of loaded zirconia implants in an animal
      model and to compare it with the behavior of titanium implants. METHODS: Five
      months after extraction of the upper anterior teeth, 12 custom-made titanium
      implants (control group) and 12 custom-made zirconia implants (test group) were
      inserted in the extraction sites in six monkeys. Before insertion, the titanium
      implant surfaces were sandblasted with Al2O3 and subsequently acid-etched. The
      zirconia implants were only sandblasted. Six months following implant insertion,
      impressions were taken for the fabrication of single crowns. A further 3 months
      later, nonprecious metal crowns were inserted. Five months after insertion of the
      crowns, the implants with the surrounding hard and soft tissues were harvested,
      histologically prepared, and evaluated under the light microscope regarding the
      peri-implant soft tissue dimensions and mineralized bone-to-implant contact.
      RESULTS: No implant was lost during the investigational period. The mean height
      of the soft peri-implant tissue cuff was 5 mm around the titanium implants and
      4.5 mm around the zirconia implants. No statistically significant differences
      were found in the extent of the different soft tissue compartments. The mean
      mineralized bone-to-implant contact after 9 months of healing and 5 months of
      loading amounted to 72.9% (SD: 14%) for the titanium implants and to 67.4% (SD:
      17%) for the zirconia implants. There was no statistically significant difference
      between the different implant materials. CONCLUSION: Within the limits of this
      animal experiment, it can be concluded that the custom-made zirconia implants
      osseointegrated to the same extent as custom-made titanium control implants and
      show the same peri-implant soft tissue dimensions.

PMID- 15515344
TI  - The comparative effect of ultrasonic scalers on titanium surfaces: an in vitro
      study.
AB  - BACKGROUND: Professional maintenance is as important for patients with dental
      implants as it is for patients with natural teeth. However, no proper maintenance
      instruments have been available for implant patients. The purpose of this in
      vitro study was to compare the effects of a new ultrasonic scaler (VR), a
      conventional ultrasonic scaler (SP), and a plastic scaler (PS) on titanium
      surfaces. METHODS: To simulate subgingival conditions, the implant healing
      abutments were connected to acrylic resin blocks with artificial gingiva using
      silicon impression material. The abutments were painted with ink as an artificial
      form of debris. The ink was removed with the VR, SP, or PS scaler for 60 seconds
      under standardized conditions, and the removal rate was calculated. The roughness
      of the abutment surface was measured with a profilometer and observed by scanning
      electron microscopy (SEM). RESULTS: The removal rate using the VR and SP scalers
      was higher than that using the PS scaler. No significant differences in the
      surface roughness or SEM observations were found among the VR, SP, or PS scalers.
      CONCLUSIONS: In this preliminary study, the new ultrasonic scaler and
      conventional ultrasonic scaler were shown to be useful for removing artificial
      debris and produced no significant damage to titanium surfaces compared to
      plastic scalers. We concluded that new and conventional ultrasonic scalers with a
      non-metal tip would be suitable for implant maintenance.

PMID- 15515346
TI  - Enhancement of periodontal tissue regeneration by transplantation of bone marrow
      mesenchymal stem cells.
AB  - BACKGROUND: The use of suitable cells transplanted into periodontal osseous
      defects appears to be a powerful strategy to promote periodontal tissue
      regeneration. Mesenchymal stem cells (MSCs) isolated from bone marrow have the
      potential for multilineage differentiation. The purpose of this study was to
      examine whether auto-transplantation of MSCs into periodontal osseous defects
      would be useful for periodontal tissue regeneration. METHODS: Bone marrow MSCs
      were isolated from beagle dogs and expanded in vitro. The expanded MSCs were
      mixed with atelocollagen (2% type I collagen) at final concentrations of 2 x
      10(6), 5 x 10(6), 1 x 10(7), or 2 x 10(7) cells/ml, and auto-transplanted into
      experimental Class III defects. Atelocollagen alone was implanted into the
      defects as a control. Periodontal tissue healing was evaluated by histological
      and morphometric analyses 1 month after transplantation. RESULTS: The defects
      were regenerated with cementum, periodontal ligament, and alveolar bone in the
      MSC-atelocollagen groups. Less periodontal tissue regeneration was observed in
      the control group compared to the MSC-atelocollagen groups. Morphometric analysis
      revealed that the percentage of new cementum length in the 5 x 10(6) and 2 x
      10(7) cells/ml groups and the percentage of new bone area in the 2 x 10(7)
      cells/ml group were significantly higher than in the control group (P < 0.01).
      CONCLUSION: These findings suggest that auto-transplantation of bone marrow
      mesenchymal stem cells is a novel option for periodontal tissue regeneration.

PMID- 15515345
TI  - Further evidence of the association between periodontal conditions and coronary
      artery disease.
AB  - BACKGROUND: There is increasing evidence that chronic infections, such as
      periodontal diseases, could play a role in the initiation and development of
      coronary artery disease (CAD). The present study was intended to test for a
      possible association between presence and severity of periodontitis and coronary
      artery disease in a Belgian population. METHODS: A total of 108 CAD patients
      (mean age 59.2 +/- 11 years) and 62 presumably healthy controls (mean age 57.7 +/
      9 years) were enrolled in the study. Probing depth, periodontal pocket bleeding
      index (PPBI), plaque index, furcation involvements, and tooth mobility were
      evaluated to compare periodontal health in both groups. The subjects were also
      ranked according to a novel index of periodontitis severity, the periodontal
      index for risk of infectiousness (PIRI), aimed at quantifying the risk of release
      of proinflammatory mediators from the periodontal sites. RESULTS: Periodontitis
      was significantly more frequent in CAD patients than in controls (CAD patients:
      91%; controls: 66%). The mean number of pockets was 18 +/- 17.1 in cardiac
      patients versus 7.6 +/- 12.7 in controls (P < 0.0001), despite the fact that the
      mean number of missing teeth was significantly greater in cases than in controls
      (14 +/- 7.1 versus 9 +/- 5.2; P < 0.0001). Furthermore, proportions of mobile
      teeth, bleeding sites, periodontal pockets, and involved furcations were
      significantly higher in CAD patients than in controls. In addition, the extent of
      the periodontal disease present was also greater in cases than in controls. A
      logistic model, adjusted for known cardiovascular risk factors, showed a strong
      association between CAD and periodontitis (odds ratio [OR] = 6.5). Moreover,
      there was a significant dose-response relationship between increasing scores of
      the periodontal risk of infectiousness and the presence of CAD (adjusted OR = 1.3
      per PIRI unit). CONCLUSION: In the present study, periodontitis was revealed to
      be a significant risk factor for CAD after adjusting for other confounding
      factors, with the level of association increasing with the individual extent of
      the periodontal lesions.

PMID- 15515347
TI  - Osseous surgery for crown lengthening: a 6-month clinical study.
AB  - BACKGROUND: Despite the fact that surgical crown lengthening is a commonly
      performed treatment, little is known about the specific surgical endpoints of the
      procedure or the stability of the newly attained crown height over time. Recent
      clinical reports have ranged across a spectrum from significant tissue rebound to
      remarkable stability using similar surgical techniques. The purpose of this study
      was to assess the stability of surgical crown lengthening procedures performed by
      various surgeons using specific guidelines to determine surgical endpoints.
      Specifically, we sought to determine the following: 1) What is the immediate
      increase in clinical crown height following surgery? 2) How stable is the
      established crown length over a 6-month period? 3) How much supporting bone is
      removed to establish the new crown length? 4) How does the position of the flap
      margin relative to the alveolar bone at surgical closure relate to the stability
      of crown height? METHODS: Twenty-five patients requiring crown lengthening of 43
      teeth were included in this study. Clinical indices recorded at eight sites on
      each molar and six sites on each premolar included plaque, bleeding on probing,
      probing depth, and relative attachment level from a customized probing stent.
      Surgical measurements at the same sites included the distance from stent to
      alveolar bone both before and after osseous surgery and the distance from flap
      margin to alveolar bone after suturing. Clinical measurements were repeated at 1,
      3, and 6 months after surgery. Sites were divided into three groups. All sites on
      teeth targeted for crown lengthening were labeled treated sites (TT).
      Interproximal sites on neighboring teeth were labeled adjacent (AA) if they
      shared a proximal surface with a treated tooth and nonadjacent (AN) if they were
      on the opposite side, away from the treated tooth. RESULTS: Throughout the entire
      6-month healing period, descriptive statistics revealed no significant time or
      group differences in plaque and bleeding scores. At treated sites, the mean gain
      of crown height at surgery was 2.27 +/- 1.1 mm. This was reduced to 1.91 +/- 1.08
      mm at 1 month, 1.69 +/- 1.02 mm at 3 months, and 1.57 +/- 1.01 mm at 6 months. At
      adjacent sites, the gain of crown length was 2.18 +/- 0.98 mm, 1.61 +/- 0.98 mm,
      1.43 +/- 0.96 mm, and 1.30 +/- 0.96 mm at surgery, 1, 3, and 6 months,
      respectively. At non-adjacent sites the crown height increased 1.06 +/- 1.07 mm,
      1.00 +/- 0.93 mm, 0.84 +/- 1.00 mm, and 0.76 +/- 0.85 mm, respectively. These
      mean measurements were significantly different for each treatment group at each
      time interval and appeared not to have stabilized between 3 and 6 months. The
      mean osseous reduction at treated, adjacent, and non-adjacent sites was 1.13 +/-
      0.90 mm, 0. 78 +/- 0.75 mm, and 0.065 +/- 0.69 mm, respectively. Frequency
      distribution of osseous reduction demonstrated that 23.6% of treated sites had 0
      mm, 44.3% had 1 mm, 25.4% had 2 mm, 6.2% had 3 mm, and less than I % had > or = 4
      mm of bone removed to establish crown height More bone removal was noted at
      premolar than at molar sites; however, this was not statistically significant.
      When tissue rebound following surgery was plotted against post-surgical flap
      position, it was noted that the closer the flap margin was sutured to the
      alveolar crest, the greater the tissue rebound during the post-surgical period.
      This rebound ranged from 1.33 +/- 1.02 mm when the flap was sutured < or = 1 mm
      from the alveolar crest, to -0.16 +/- 1.15 mm when the flap was sutured > or = 4
      mm from the alveolar crest. CONCLUSIONS: These data suggest that there is a
      significant tissue rebound following crown-lengthening surgery that has not fully
      stabilized by 6 months. The amount of tissue rebound seems related to the
      position of the flap relative to the alveolar crest at suturing. These findings
      support the premise that clinicians should establish proper crown height during
      surgery without overreliance on flap placement at the osseous crest.

PMID- 15515348
TI  - Undifferentiated malignant neoplasm involving the interdental gingiva: a case
      report.
AB  - BACKGROUND: Metastases to the gingiva are uncommon. They can be a diagnostic
      challenge clinically because of their rarity and tendency to mimic benign
      lesions. In this report, we present a case of an undifferentiated malignant
      neoplasm of unknown origin presenting as benign inflammatory gingival lesions and
      we review the literature on metastases to the gingiva. METHODS: A 44-year-old
      female patient was referred by a local periodontist for evaluation of multiple
      painless gingival lesions that clinically resembled pyogenic granulomas or
      periodontal abscesses, but with an uncharacteristic multifocal presentation in
      the background of good oral hygiene. Her medical history was unremarkable except
      for recent weight loss. Periapical radiographs were obtained, as well as two
      incisional biopsies, one placed in formalin for routine histology and
      immunohistochemistry, the other in phosphate buffered saline for flow cytometry.
      RESULTS: Radiographic findings were non-contributory for hard tissue pathoses.
      Histopathological findings were consistent with a poorly differentiated
      malignancy, suggestive of metastatic disease. Immunohistochemical studies and
      flow cytometry were unsupportive in delineating any tumor differentiation. The
      patient subsequently developed multiple tumors throughout the body with similar
      histopathological findings, yet no primary tumor was identified and a definitive
      diagnosis could not be rendered. She was discharged one month later in poor
      condition with the principal diagnosis of hemorrhage/ pancytopenia, and a
      secondary diagnosis of metastatic head and neck cancer. CONCLUSION: This case of
      malignant metastatic tumor of unknown origin presenting as benign gingival
      lesions illustrates the importance of thorough patient evaluation, which should
      include a biopsy when necessary for definitive diagnosis.

PMID- 15515349
TI  - The international scene: a pediatric perspective.

PMID- 15515350
TI  - International child health.
AB  - It is our hope that this issue of Pediatric Annals will stimulate among readers a
      desire to learn more about the difficult challenges faced by our colleagues who
      live and work in developing countries. They do so much with so little, and their
      dedication to their work is an inspiration to us all. Armed with such
      information, working as individuals and as members of political, educational,
      charitable, and service organizations, we can help many of the children who
      otherwise will be lost without our attention.

PMID- 15515351
TI  - A 14-month-old boy with prolonged fever and splenomegaly.

PMID- 15515352
TI  - Protecting Child Health Worldwide. Implementation is the biggest challenge
      slowing efforts to reduce childhood morbidity and mortality in developing
      countries.
AB  - Children in developing countries bear most of the burden of childhood death and
      disease. Because decades of technical and medical research have produced
      solutions to most of the serious health problems affecting such children, the
      main challenge ahead remains one of implementation. Achieving this goal will
      almost certainly require significantly greater commitment by the nations,
      organizations, and individuals who have the ability to help.

PMID- 15515353
TI  - Child nutrition in developing countries.
AB  - Malnutrition permeates all aspects of health, growth, cognition, motor and social
      development of young children in developing countries. More than 50% of deaths in
      these children can be attributed to malnutrition, most often in conjunction with
      serious infection. Irreversible and lifelong sequelae prevent children from
      reaching their full potential. Child survival initiatives and programs have
      accomplished much to save the lives of children from common and preventable
      illnesses, but the quality of the survivors' health needs to be improved, with
      much more attention paid to nutrition of the preschool and school child.
      Promotion of nutritional health must become an integral part of primary health
      services, especially for infants, preschoolers, schoolchildren, and women.
      Promotion of exclusive breastfeeding and appropriate complementary feeding and
      weaning are essential inputs. A daunting challenge is to improve diet quality
      through the raising and consumption of small animals by rural subsistence
      households to enhance maternal and child nutrition. School feeding from preschool
      onward must be an integral part of education so children are in a condition to
      learn. An excellent example of such programs is the WHO initiated Integrated
      Management of Childhood Illness, which integrates nutrition into the care of both
      sick and well children. The Early Child Development Program initiated by the
      World Bank and UNICEF has taken hold in many countries. Nutrition outcomes are
      closely linked with health and education activities starting in the preconception
      period through pregnancy, lactation, and childhood. Investment in human capital
      early in life will optimize the growth and social and economic development of
      children, families, and communities.

PMID- 15515354
TI  - Preparing children for travel to tropical and developing regions.
AB  - Visiting a grandparent for a first time, exploring the ruins of an ancient
      civilization in a distant country, or river rafting through a tropical jungle are
      all moments that are never forgotten. Illness, visits to the doctor, and
      disability should not be a part of these experiences. Diseases such as malaria,
      yellow fever, travelers' diarrhea, and hepatitis A are preventable. Through the
      use of vaccines, prophylactic medications, and disease-prevention education,
      clinicians may help ensure their pediatric patients have enjoyable and rewarding
      travel experiences.

PMID- 15515355
TI  - Childhood turberculosis in the developing world.
AB  - Tuberculosis remains an important cause of childhood morbidity and mortality in
      many areas of the developing world. Published data on the epidemiology of TB in
      children are scarce, and research efforts focused on TB in children are too few.
      The diagnosis of TB in children is difficult, and too many children are not
      completing their prescribed courses of treatment. Controlling TB in all
      populations requires that attention be devoted to the issues of accurate
      surveillance and adequate diagnosis and treatment of TB in children.

PMID- 15515357
TI  - International volunteer work for the practicing pediatrician.

PMID- 15515356
TI  - Childhood turberculosis: reflections from the front line.
AB  - Tuberculosis is a major cause of childhood morbidity and mortality in high-burden
      settings, particularly in the third-world settings. Effective intervention in
      these resource-limited areas requires a clear focus on high-risk groups. Children
      rarely contribute to disease transmission, but their disease is the direct result
      of continued transmission within the community. The burden of childhood
      tuberculosis reflects the level of epidemiological control achieved within the
      adult population. Adequate diagnosis and treatment should be available for every
      child, but reducing the burden of childhood disease requires a concerted effort
      to contain the epidemic.

PMID- 15515358
TI  - Psychosocial care of severely malnourished children. A hospital in Haiti has
      greatly improved the prospects for the children it treats.
AB  - The psychosocial intervention program for malnourished children at Hopital Albert
      Schweitzer has evolved over several years and now consists of daily interventions
      including music on the unit, cooking and feeding instruction, exercise sessions,
      supervised play sessions, daily massage of children by their parents, toy making,
      and singing and dancing. The interventions are supervised by Haitian personnel
      and have been developed according to what is interesting and stimulating for
      Haitian parents and their children. These interventions appear to have greatly
      improved the moods of the parents and their children. They seem happier. There is
      more interaction between the parents and the children throughout the day,
      including touching, playing, and talking. The feeding situation has improved.
      Parents feed their children; there is more socializing and eye contact during
      meals. Our experience supports the concept that the rehabilitation of the
      malnourished child is facilitated by interventions that restore a positive parent
      child relationship. These interventions should be tailored to the local culture.
      Future studies could evaluate the effect of such interventions on the parent
      child interaction at the beginning and end of the hospitalization, as well as on
      parameters such as mortality, rate of weight gain, length of stay, and
      readmission rates.

PMID- 15515359
TI  - Pediatricians and the Rights of the Child. UN Convention provides blueprint for
      monitoring the well-being of children worldwide.
AB  - The Convention should have a special resonance for pediatricians and others who
      have both the capacity and responsibility to care for children. A basic tenet of
      pediatric practice is to advocate for the best interests of the child. According
      to the Convention, this does not mean that a child's interests will always
      prevail; rather, it allows for child interests to be considered and given equal
      weight to competing interests. The pediatric community could benefit in this
      regard by using a human rights perspective to inform the public debate on
      children's issues. Pediatricians use growth charts in their daily practices to
      compare a child's growth to norms for his or her particular age and gender. One
      may think of the Convention as the growth chart for children's interests, a
      template by which child advocates can measure progress in promoting the health
      and well-being of children.

PMID- 15515360
TI  - Volunteering abroad enriches resident's education.

PMID- 15515361
TI  - An overview of allergens.

PMID- 15515362
TI  - Skin testing in allergy.

PMID- 15515363
TI  - Allergen immunotherapy: definition, indication, and reactions.

PMID- 15515364
TI  - Stinging insect allergy and venom immunotherapy.

PMID- 15515365
TI  - Allergic rhinitis.

PMID- 15515366
TI  - Nonallergic rhinitis.

PMID- 15515367
TI  - Nasal polyps.

PMID- 15515368
TI  - Sinusitis.

PMID- 15515369
TI  - Asthma classification.

PMID- 15515370
TI  - Pediatric asthma: principles and treatment.

PMID- 15515371
TI  - Asthma: principles of treatment.

PMID- 15515372
TI  - Potentially fatal asthma.

PMID- 15515373
TI  - Status asthmaticus.

PMID- 15515374
TI  - Asthma in pregnancy.

PMID- 15515375
TI  - Occupational immunologic lung disease.

PMID- 15515376
TI  - Allergic bronchopulmonary aspergillosis.

PMID- 15515377
TI  - Hypersensitivity pneumonitis.

PMID- 15515378
TI  - Atopic dermatitis.

PMID- 15515379
TI  - Urticaria and angioedema.

PMID- 15515380
TI  - Hereditary and acquired angioedema.

PMID- 15515381
TI  - Food allergy.

PMID- 15515383
TI  - Idiopathic anaphylaxis.

PMID- 15515382
TI  - Anaphylaxis.

PMID- 15515384
TI  - Common in vitro tests for allergy and immunology.

PMID- 15515385
TI  - Approach to primary immunodeficiency.

PMID- 15515386
TI  - Unproved methods and theories in allergy.

PMID- 15515387
TI  - [Educational crisis within gastrointestinal surgery. The solution is not only
      longer working hours, but also reduced number of younger surgeons-trainees. The
      condition is centralized emergency surgery].

PMID- 15515388
TI  - [Orbital decompression surgery for severe thyroid-associated orbitopathy].

PMID- 15515389
TI  - [Molecular colon diagnostics--when can we get a gastroenterological weather
      report?].

PMID- 15515390
TI  - [Approaches to diagnosis and treatment of dyspepsia].

PMID- 15515391
TI  - [Chronic idiopathic thrombocytopenic purpura].

PMID- 15515392
TI  - [Idiopathic thrombocytopenic purpura. A retrospective evaluation of 68 patients].

PMID- 15515393
TI  - [Orbital decompression surgery for severe thyroid-associated orbitopathy: A
      follow-up study].

PMID- 15515394
TI  - [Frequent drug interactions in general practice].

PMID- 15515395
TI  - [Eradication of Helicobacter pylori and use of antisecretory drugs--a population
      based study].

PMID- 15515396
TI  - [Bandaging of extremities].

PMID- 15515397
TI  - [Recurrence of purulent meningitis in a patient with dorsal dermal sinus].

PMID- 15515398
TI  - [Ultrasound doppler diagnosis of herniation through the linea alba].

PMID- 15515399
TI  - [Uterine rupture at vaginal birth after Caesarean section].

PMID- 15515400
TI  - [Welcome education].

PMID- 15515401
TI  - [Self help in connection with nocturnal urination].

PMID- 15515402
TI  - [Eli Lilly plans to create a public research registry].

PMID- 15515403
TI  - [Minerva's owl flies first at dusk].

PMID- 15515404
TI  - Physiology and pathophysiology of the 5-HT3 receptor.
AB  - The 5-HT3 receptor is a ligand-gated cation channel located in the central and
      peripheral nervous system; it has also been detected on a variety of other cells.
      In the periphery, it is found on autonomic neurons and on neurons of the sensory
      and enteric nervous system. In the CNS, the 5-HT3 receptor has been localized in
      the area postrema, nucleus tractus solitarii, nucleus vaudatus, nucleus
      accumbens, amygdala, hippocampus, entorhinal, frontal, cingulate cortex, and in
      the dorsal horn ganglia. Further extraneuronal locations include among others
      lymphocytes, monocytes, and foetal tissue. 5-HT3 receptors modulate the release
      of neurotransmitters and neuropeptides like dopamine, cholecystokinin,
      acetylcholine, GABA, substance P, and serotonin itself. They have been
      demonstrated to be involved in sensory transmission, regulation of autonomic
      functions, integration of the vomiting reflex, pain processing and control of
      anxiety. While the physiologic functions of the 5-HT3 receptor are discrete and
      difficult to detect, it plays a key role in certain pathologic situations related
      to increased serotonin release. Clinical development of 5-HT3 receptor
      antagonists revealed a remarkable range of activities. 5-HT3 receptor antagonists
      do not modify any aspect of normal behaviour in animals or induce pronounced
      changes of physiological functions in healthy subjects. Clinical efficacy was
      shown for various forms of emesis like chemotherapy-induced, radiotherapy
      induced, and postoperative emesis, diarrhoea-predominant irritable bowel
      syndrome, anxiety, chronic fatigue syndrome, alcohol abuse, and in pain syndromes
      such as fibromyalgia and migraine. Most recent data also suggest that 5-HT3
      receptor antagonists are effective for the treatment of other rheumatic diseases
      such as rheumatoid arthritis, tendinopathies, periarthropathies, and myofascial
      pain. Other possible indications under discussion are chronic heart pain and
      bulimia. Unfortunately, experimental findings do not yet provide a homogenous
      conception of the significance of 5-HT3 receptors in all investigated fields; in
      nociception, for example, contradictory observations are still inadequately
      explained and complicated by bell-shaped dose-response curves. Further
      elucidation and better understanding of the serotonergic neuronal network remains
      a task for the next decade.

PMID- 15515405
TI  - Expression of 5-HT3A receptors in cells of the immune system.
AB  - There is evidence from both human and animal research that 5-hydroxytryptamine3
      (5-HT3) receptor antagonists, particularly tropisetron, exert analgesic and
      antiinflammatory effects. However, the underlying mechanisms of these effects
      including the expression of 5-HT3 receptors in cells of the immune system have
      not yet been investigated in detail. Therefore, we investigated the expression of
      the 5-HT3A receptor in primary human monocytes, chondrocytes, T-cells, dendritic
      cells, and synovial tissue. We found that 5-HT3A receptors are expressed in
      monocytes, chondrocytes, T-cells, and synovial tissue but not in dendritic cells.
      Our data show that 5-HT3A receptors are widely expressed in cells of the immune
      system and that they might play an important role in inflammatory events and in
      the observed antiphlogistic effects of 5-HT3 receptor antagonists.

PMID- 15515406
TI  - Spectrum of use and tolerability of 5-HT3 receptor antagonists.
AB  - Several 5-HT3 receptor antagonists are available (tropisetron, ondansetron,
      granisetron, dolasetron, and palonsetron), and further compounds are in clinical
      development. These substances show only minor differences in the activity profile
      regarding their affinity for particular receptors. 5-HT3 receptor antagonists are
      primarily used and found effective in the prevention and treatment of
      chemotherapy-induced nausea and emesis, and in postoperative nausea and vomiting
      (PONV). Antagonism of the 5-HT3 receptors in the peripheral and central nervous
      system is a probable mechanism of action. The substances are suitable as first
      line therapy (combined with a corticosteroid) for the prevention of acute nausea
      and vomiting in patients treated with moderately to severely emetogenic
      chemotherapeutic agents. This combination is also moderately effective in the
      prevention of delayed nausea and vomiting. 5-HT3 receptor antagonists are an
      important constituent in the prevention and treatment of emesis and nausea caused
      by radiation therapy, especially in patients receiving whole body or upper
      abdominal treatment. Alosetron was found clinically effective in diarrhoea
      predominant irritable bowel syndrome, whereas tropisetron in fibromyalgia and
      related pain disorders. Further indications for such treatment include anxiety
      disorders, alcohol dependence, drug withdrawal, and psychosis related to
      treatment of Parkinson's disease. 5-HT3 receptor antagonists are well tolerated
      with the most frequently reported adverse effects being headache, constipation,
      dizziness, tiredness, and gastrointestinal disturbances such as abdominal pain or
      constipation. Intravenous administration of serotonin induces the Bezold-Jarisch
      reflex and causes small reversible changes in electrocardiogram (ECG) parameters.

PMID- 15515407
TI  - Analgesic effects of 5-HT3 receptor antagonists.
AB  - Current research suggests an involvement of 5-HT3 receptors in peripheral and
      central perception and processing of pain as well as in inflammation. Tropisetron
      and other selective 5-HT3 receptor antagonists have been used successfully for
      pain reduction and treatment of related symptoms in patients diagnosed with
      fibromyalgia. This article proposes a concept of the underlying pathophysiology
      and mechanisms of action of 5-HT3 receptor antagonists in the context of the
      relevant clinical data on their application in patients with rheumatic disease.

PMID- 15515408
TI  - The influence of the 5-HT3 receptor antagonist tropisetron on pain in
      fibromyalgia: a functional magnetic resonance imaging pilot study.
AB  - OBJECTIVE: Central pain processing is altered in patients with fibromyalgia
      syndrome (FMS). The serotonin metabolism, especially the 5-HT3 receptor, seems to
      play an important role. METHODS: We investigated the effect of the local
      injection of the 5-HT3 receptor antagonist tropisetron on the perception and
      central processing of pain in FMS patients using painful mechanical stimulation
      and functional magnetic resonance imaging (fMRI) within the framework of a pre
      /posttreatment double-blind design. RESULTS: In the contralateral primary
      somatosensory cortex, contralateral posterior insula, and anterior cingulate
      cortex, we found that the activation was significantly reduced after treatment.
      On average, patients rated the stimulation-induced pain intensity as stronger in
      the session after treatment compared to before treatment, although the individual
      data revealed a heterogeneous pattern. All patients showed sensitisation during
      the painful stimulation, which was not influenced by the treatment. CONCLUSIONS:
      Both the sensory-discriminative and motivational-affective components of pain as
      measured by fMRI were altered by tropisetron.

PMID- 15515409
TI  - Antiinflammatory effects of 5-HT3 receptor antagonists in lipopolysaccharide
      stimulated primary human monocytes.
AB  - There is evidence from both human and animal research that 5-hydroxytryptamine (5
      HT)3 receptor antagonists, particularly tropisetron, exert analgesic and
      antiinflammatory effects. However, the underlying mechanisms of these effects
      have not yet been investigated in detail. Therefore, the antiinflammatory effects
      of tropisetron and ondansetron were investigated in human monocytes. In human
      monocytes, both lipopolysaccharide (LPS)-stimulated tumour necrosis factor (TNF)
      alpha and interleukin (IL)-1beta secretion were dose-dependently inhibited by
      tropisetron starting at a concentration of 5 microg/mL and reaching maximal
      levels at 25 microg/mL (IC50: 32 microg/mL and 12 microg/mL, respectively). LPS
      induced IL-6 and PGE2 release was only slightly inhibited at high doses, whereas
      LPS-induced release of IL-8 and matrix metalloprotease (MMP)-9 was not affected.
      In conclusion, our data show that the binding of tropisetron to 5-HT3 receptors
      results in antiinflammatory effects through inhibition of TNF-alpha/IL-1beta,
      which might explain the antiphlogistic effects of 5-HT3 antagonists.

PMID- 15515410
TI  - Tropisetron inhibits serotonin-induced PGE2 release from macrophage-like synovial
      cells in serum-free tissue culture.

PMID- 15515411
TI  - Immunomodulatory function of the 5-HT3 receptor antagonist tropisetron.
AB  - OBJECTIVE: To characterize the immune modulatory effects of 5-HT3 receptor
      antagonist treatment in patients with fibromyalgia, autoimmune disorders, and
      chronic pain. METHODS: Multiplex-assisted cytokine measurements were performed
      before and during treatment. Whole blood stimulation with TNF-alpha was carried
      out to determine the proinflammatory response induced by exogenous TNF-alpha.
      RESULTS: Five of nine patients clinically responded to treatment, and two had a
      moderate response. All patients had significantly elevated levels of T-H1
      cytokines more prominent than TNF-alpha, IL-1beta, and IL-6. Treatment resulted
      in transient effects on peripheral monocyte counts in all but one patient, a
      plasma IL-1beta increase in two responder patients, and decreased T-H1 cytokines
      in two responder patients. Ex vivo TNF-alpha stimulation was transiently
      reconstituted in three responder patients to a significant level. Three patients
      showed a marginal reconstitutive response. CONCLUSION: 5-HT3 receptor blockade
      transiently affects monocyte tissue infiltration, modulates T-H1 cytokines in
      clinical responders as well as MIP-1beta in moderate responders, and transiently
      affects the ex vivo response to exogenous TNF-alpha.

PMID- 15515412
TI  - Influence of tropisetron on the serum substance P levels in fibromyalgia
      patients.
AB  - BACKGROUND: Substance P is found at an elevated level in the cerebrospinal fluid
      of fibromyalgia (FM) patients. Treatment with tropisetron leads in a subgroup of
      FM patients to pain reduction. The question arises of whether the substance P
      level in the serum can be changed by tropisetron treatment. METHOD: Twenty
      patients with FM diagnosed according to the ACR criteria were treated for 5 days
      with a 5 mg tropisetron intravenous (i.v.) bolus injection daily. Before the
      first injection, 3 h later, and before and 3 h after the last injection, the
      serum levels of substance P were determined. The determination of this substance
      was carried out by means of an immunoassay from Assay Design Biotrend, Cologne.
      To evaluate the success of the tropisetron treatment, patients made a global
      assessment as 'clearly better', 'better', 'unchanged', or 'poor'. Patients who
      answered 'clearly better' and 'better' were regarded as responders. RESULTS: Of
      the 20 patients, ten reported a good or very good influence on their pain
      (responders). In these responders, the means of the serum substance P levels were
      elevated in comparison with the non-responders, though the difference was not
      significant. In responders, the 5-HT3 receptor antagonist tropisetron produced a
      significant decrease in the serum substance P levels, while this did not occur in
      the non-responders. CONCLUSION: It is possible that the responders to tropisetron
      represent a subgroup of FM patients for whom substance P and 5-HT3 receptors play
      key roles in the development of the pain symptoms.

PMID- 15515413
TI  - Local treatment of tendinopathies and myofascial pain syndromes with the 5-HT3
      receptor antagonist tropisetron.
AB  - The use of local tropisetron injections improved the treatment of tendinopathies
      considerably, with the effect being comparable to the topical application of
      local anaesthetics combined with depot corticosteroids. On the other hand, local
      injection of prilocaine alone exerted a shorter and weaker effect on the
      condition. OBJECTIVES: After it had been proven that systemic application of the
      5-HT3 receptor antagonist tropisetron exerts an analgesic effect on
      musculoskeletal pain in fibromyalgia, we investigated the efficacy of the
      substance in tendinopathies and myofascial pain syndromes. RESULTS: Local
      injections of tropisetron as a treatment for trigger points in myofascial pain
      syndrome also brought about rapid and prolonged relief in the majority of cases.
      The analgesic effect was far superior to the action of local anaesthetics.
      CONCLUSION: The present findings indicate that the analgesic action of the 5-HT3
      receptor antagonist tropisetron sets in rapidly and lasts for a long time.
      Various mechanisms are under discussion to explain the long duration of the
      effect. Tropisetron not only has an analgesic but probably also an antiphlogistic
      effect which can be attributed to the inhibited release of substance P and other
      neuropeptides from the nociceptors and the blocked release of phlogistic
      substances from macrophages, monocytes etc.

PMID- 15515414
TI  - Trigger point injection treatment with the 5-HT3 receptor antagonist tropisetron
      in patients with late whiplash-associated disorder. First results of a multiple
      case study.
AB  - Preliminary results of an ongoing study on the effectiveness of trigger point
      injections with tropisetron in 20 patients with late whiplash-associated disorder
      are presented. The study demonstrated more than 50% pain relief for more than 2
      weeks in 52% of the 73 treatment sessions. The duration of effectiveness of the
      injections showed great intraindividual and interindividual variation.

PMID- 15515416
TI  - Serotonin type 3 receptor antagonist tropisetron in the treatment of chronic
      inflammatory rheumatic conditions--preliminary clinical experience.
AB  - Several lines of research indicate that serotonin (5-hydroxytryptamine, 5-HT) and
      5-HT receptors may play a part in the pathogenesis of chronic inflammatory
      rheumatic conditions like rheumatoid arthritis (RA) and scleroderma/progressive
      systemic sclerosis (PSS). In this paper, case reports on two patients with RA who
      were successfully treated with 5-HT3 receptor antagonist tropisetron were
      presented. Short-term oral tropisetron (5-10 mg/d) induced either remission of RA
      or improvement in RA-related symptoms, which lasted for several weeks or months
      after the treatment was discontinued. Interestingly, tropisetron was effective in
      a patient with refractory rheumatoid vasculitis, which is a severe complication
      that requires high-dose glucocorticoids in most cases. The beneficial effect of 5
      HT3 receptor antagonists in RA and PSS suggests that this class of drugs may have
      potential in the treatment of chronic inflammatory rheumatic conditions. Double
      blind, placebo-controlled studies are urgently needed to confirm the efficacy and
      tolerance of 5-HT3 receptor antagonists in larger cohorts of patients.

PMID- 15515415
TI  - Intra-articular treatment of arthritides and activated osteoarthritis with the 5
      HT3 receptor antagonist tropisetron. A double-blind study compared with
      methylprednisolone.
AB  - BACKGROUND: Since the good effect of intra-articular injections of the 5-HT3
      receptor antagonist tropisetron in patients with arthritides and activated
      osteoarthritis has already been demonstrated in pilot studies, the effect of
      tropisetron is compared with that of methylprednisolone here. OBJECTIVES: In a
      double-blind study, 34 patients with gonarthritides or activated osteoarthritis
      (18 patients with rheumatoid arthritis, 16 patients with osteoarthritis) were
      treated with a single intra-articular injection of 10 mg tropisetron (18
      patients) or 40 mg methylprednisolone (16 patients). Before treatment as well as
      one and three weeks later, the intensity of rest pain and pain following exercise
      was measured with the visual analog scale (VAS) for pain and the clinical
      findings in the knee joint were recorded. RESULTS: By means of the intra
      articular tropisetron treatment, the inflammatory joint process with arthritides
      and activated arthroses could be influenced in a similar way as with
      corticosteroid treatment. No significant differences were detected. CONCLUSION:
      According to the results presented here, the intra-articular treatment with the 5
      HT3 receptor antagonist tropisetron in patients with gonarthritides and activated
      arthroses was about equally effective as those for treatment with
      corticosteroids. Therefore, it can be used as an alternative in patients for whom
      concomitant diseases like diabetes and hypertension make it difficult to use
      corticosteroids. Whether increasing the tropisetron dose may further improve the
      results remains to be determined in future studies.

PMID- 15515417
TI  - Treatment of systemic sclerosis with the 5-HT3 receptor antagonist tropisetron.
AB  - BACKGROUND: There is no known disease-modifying therapy for progressive systemic
      sclerosis. OBJECTIVES: It was shown that a patient with secondary fibromyalgia
      syndrome for whom the development of systemic sclerosis was suspected because of
      a Raynaud's phenomenon and the presence of SCL-70 antibodies in the serum had
      experienced a clear pain reduction under treatment with tropisteron, which is the
      reason why this drug was also used with established systemic sclerosis. METHOD:
      Two patients with progressive systemic sclerosis and positive SCL-70 antibodies
      were treated for 6 weeks with 5 mg tropisetron daily. Both patients had clear
      skin symptoms, functional impairments of the locomotor system, and a secondary
      fibromyalgia syndrome. The skin score and joint motion were checked before,
      during, and after treatment. In addition, the patients filled in the visual
      analog scale for pain at these times. At the end of the 6 weeks, the patients
      showed a clear improvement of the skin score and the movability of various joints
      as well as a clear reduction of pain. The medication was well-tolerated.
      Constipation developed in the patients; it could be controlled with laxatives.
      Follow-up questioning of the patients after 3 months showed that their condition
      had remained stable. CONCLUSION: Two patients with progressive systemic sclerosis
      showed an improvement of various symptoms under a blockade of the 5-HT3 receptors
      via tropisetron. The long-lasting effect pointed to immunomodulation. The two
      cases give cause for clarifying this by means of clinical studies, which should
      also investigate the question of dosage (possibly 5 mg tropisetron twice daily).

PMID- 15515418
TI  - Treatment of fibromyalgia with tropisetron--dose and efficacy correlations.
AB  - Previous studies evaluating the efficacy and tolerance of tropisetron for the
      treatment of fibromyalgia (FM) used the drug either intravenously or orally, and
      at different dosage levels ranging from 2 mg to 15 mg daily. The shortest
      treatment was a single dose and the longest treatment period covered 28 days. A
      significant reduction of the pain intensity was achieved by using tropisetron 5
      mg per day. Apart from the fact that treatment periods were different, the
      efficacy of oral and intravenous administration did not differ significantly.
      Tropisetron was well tolerated; but in the 15 mg group in one of the studies, the
      decrease in pain was less than in the placebo group, however, the frequency of
      constipation and other gastrointestinal symptoms increased. Furthermore, it was
      hypothesized that due to the impacts of CYP2D6 activities, a daily dose of
      tropisetron 2 mg may be efficacious in slow metabolizers only. Although
      tropisetron proved to be efficacious in a group of fibromyalgia patients, the
      dose-response curves cannot yet be explained in a fully satisfactory manner,
      which may encourage research focusing on possible subgroups of FM.

PMID- 15515419
TI  - The assessment of vegetative and functional symptoms in fibromyalgia patients:
      the tropisetron experience.
AB  - Vegetative and functional symptoms are, besides pain and tenderness of tender
      points, considered as additional information for the diagnosis of fibromyalgia
      (FM). In clinical trials, vegetative and functional symptoms have been included
      for selection of patients (e.g. sleep disturbances) and as secondary outcome
      parameters. Despite the relevance of these symptoms, no validated method is
      currently available but symptom lists are ad hoc developed by investigators. In
      this manuscript, data from a published double blind, randomised study are
      reanalysed which compared oral therapy over 10 days with 5 mg, 10 mg, and 15 mg
      to placebo in FM patients. This study applied a list of 17 vegetative and
      functional symptoms, which had to be scored by the patients by use of a 4-point
      severity scale (0 = none to 3 = severe). Factor analysis of the baseline data
      from 195 patients suggested to separate 6 sub-scales: Cardiovascular,
      gastrointestinal, psychiatric (sleep disturbance), nervous, autonomic system, and
      general disorders. Sleep disturbances, general symptoms (morning stiffness,
      fatigue) and autonomic symptoms (cold extremities, hyperhidrosis) were most
      severe in intensity. Analysis of sensitivity for treatment effects made use of
      differences between placebo and 5 mg tropisetron in changes between baseline and
      final assessment of the tropisetron trial. While, on the item level, differences
      in favour of tropisetron could only be demonstrated for sleep disorders, on the
      sub-scale level, also favourable effects of tropisetron could be shown for
      cardiovascular and nervous system complaints and, as a tendency, for general
      symptoms. On the other side, the sub-scale score of gastrointestinal symptoms
      worsened under tropisetron whilst it improved under placebo which effect was due
      to side effects of the active treatment. It is concluded that symptom clusters
      like sub-scales of a list of vegetative and functional symptoms will be more
      suitable for diagnostic purposes and evaluation of treatment outcome of clinical
      trials. Further research is urgently required which addresses the development of
      a FM-specific scale to assess vegetative and functional symptoms.

PMID- 15515420
TI  - Intravenous treatment of fibromyalgia with the 5-HT3 receptor antagonist
      tropisetron in a rheumatological practice.
AB  - In 223 fibromyalgia (FM) patients in a rheumatology practice, a follow-up postal
      survey was carried out 0.5-2 years after a 5-day intravenous (i.v.) treatment
      with 5 mg of the 5-HT3 receptor antagonist tropisetron daily on the effect of
      this treatment. 121 patients returned the completed questionnaire. After
      subtraction of 22 undeliverable questionnaires, this represented 60.2% of
      patients contacted for whom an assessment of the tropisetron treatment was
      possible. A good to very good effect of the treatment on the pain was reported by
      45% of the patients, and only 25% reported an unsatisfactory effect. The effect
      of tropisetron IV lasted between one day and 12 weeks (mean 8.6 +/- 13.6 d).
      Sleep and general condition were also assessed as good or very good by almost
      half of the patients. The tolerance of tropisetron was generally good. In
      comparison with the current treatment and the best treatment with other drugs
      ever received, tropisetron was rated as more efficacious in almost half of the
      cases, though an unsatisfactory effect of tropisetron compared to other
      treatments was reported in 30% of the cases. Considered in comparison to less or
      at most equally efficacious alternatives, according to this open respective
      study, IV tropisetron treatment represents a promising option for the treatment
      of FM even though the study design incorporated many imponderables. Particularly
      the question of whether the success of treatment can be improved further with a
      longer lasting treatment or a selection of the patients still needs to be
      settled.

PMID- 15515421
TI  - Treatment of chronic low back pain with tropisetron.
AB  - BACKGROUND: Various pathophysiological processes can lead to chronic back pain,
      which necessitates a differentiated therapeutic approach. In addition, psychic
      and psychosocial processes may influence the clinical picture. METHOD: Twenty
      five patients with chronic back pain were enrolled in the study. Patients
      suffering from psychosocial stresses and depressions were excluded from the
      study. The patients with painful tendinopathies and myofascial pain syndromes
      were treated with local injections of 5-10 mg tropisetron, and patients with
      degenerative processes were treated for 5 days with an intravenous (i.v.) bolus
      injection of 5 mg tropisetron (Navoban). Before treatment and 7 and 14 days
      later, the visual analog pain scale was filled in. The long-term drug therapy
      could be continued. RESULTS: There was a highly significant pain reduction with a
      very potent effect both in the locally treated group and in the intravenously
      treated group. Most of the patients could discontinue or reduce their long-term
      therapy with non-steroidal anti-inflammatory drugs or analgesics. CONCLUSION: A
      marked improvement in pain could be achieved in an open study by treating back
      pain of a primarily somatic nature with the 5-HT3 receptor antagonist
      tropisetron. A reduction in pain of > or =50% was reported by 76% of the
      patients. These results should be substantiated by the corresponding randomized,
      placebo-controlled, double blind studies that are needed to investigate the true
      benefit of treating back pain with 5-HT3 receptor antagonists.

PMID- 15515422
TI  - Concluding remarks and outlook for the use of 5-HT3 receptor antagonists in
      rheumatology.

PMID- 15515423
TI  - Relationships between local and systemic expression of interleukin-12 and plasma
      levels of vascular endothelial growth factor in patients with gastric cancer.
AB  - BACKGROUND: Interleukin 12 (IL-12) is a heterodimeric cytokine that exhibits
      potent anti-tumor and anti-metastatic activities. Very few studies have
      investigated the expression of IL-12 in patients with gastric cancer. The purpose
      of the present study was to evaluate the immunohistochemical expression and serum
      levels of IL-12, and plasma levels of vascular endothelial growth factor (VEGF)
      in patients with gastric cancer. PATIENTS AND METHODS: IL-12 was
      immunohistochemically stained using monoclonal anti-human IL-12 antibody (1-1A4)
      in surgical specimens of 27 gastric cancer patients. IL-12-positive cells were
      counted and positive cell density was calculated. Blood was obtained before
      surgery. Serum levels of IL-12 and plasma levels of VEGF were assessed using the
      quantitative sandwich enzyme immunoassay technique. The relationships of IL-12
      positive cell density, serum levels of IL-12, plasma levels of vascular
      endothelial growth factor (VEGF) and clinicopathological factors were evaluated.
      RESULTS: Although IL-12-positive cell density was not associated with serum
      levels of IL-12, the IL-12-positive cell density tended to increase in patients
      with serum levels of IL-12 higher than the mean level (p=0.0518). IL-12-positive
      cell density significantly decreased in the patients with CEA positive or
      differentiated type. Moreover, IL-12-positive cell density tended to be inversely
      correlated with plasma levels of VEGF (p=0.0801, r=-0.343). CONCLUSION: These
      results suggest that the immune efficiency in patients with gastric cancer may be
      reflected by IL-12-positive cell density and serum levels of IL-12. Thus,
      patients with low IL-12-positive cell density or serum levels of IL-12 in gastric
      cancer may require additional immunochemotherapy after surgery.

PMID- 15515424
TI  - Biological effect of OK-432 (picibanil) and possible application to dendritic
      cell therapy.
AB  - OK-432 (Picibanil), a streptococcal preparation with potent biological response
      modifying activities, was approved in Japan as an anticancer agent in 1975. In
      the ensuing 30 years, since then, a significant amount of data, including
      clinical as well as experimental studies, has been accumulated. OK-432 has been
      reported to induce various cytokines, activate immunological cells and thus
      augment anticancer immunity. Recently, the interrelation between innate immunity
      and adaptive immunity has become clear and it was reported that OK-432 acts, at
      least in part, via Toll-like receptor (TLR) 4-MD2 signaling pathway. In addition,
      dendritic cells (DCs) are considered to play a pivotal role in immunological
      response and it is reported that OK-432 induced maturation of DCs both in vitro
      and in vivo. These results suggest that OK-432 is a useful adjuvant in DC-based
      anticancer immunotherapy. Clinical studies of DC therapy with OK-432 are under
      way.

PMID- 15515425
TI  - A report of three patients treated with immunocell therapy with imatinib
      mesylate.
AB  - BACKGROUND: Immunocell therapy has been applied to patients with refractory
      cancer in clinical trials or as an unconventional cancer therapy, however the
      efficacy is still limited. To improve this efficacy, a combination therapy may be
      beneficial. Molecularly-targeted therapy acts directly on neoplasm cells to
      suppress their growth without causing myelosuppression. CASE REPORT: Recently, we
      encountered three patients treated by immunocell therapy with imatinib mesylate
      (Glivec). One patient was diagnosed as having Philadelphia chromosome (Ph) (+)
      acute lymphoblastic leukemia (ALL) and had a relapse-free survival of more than
      24 months. The other two were diagnosed as having GIST; a partial response was
      observed in one which lasted more than 21 months, while the other's disease has
      been stabilized for more than 25 months. No side-effects were observed, other
      than those mentioned in the directions for the use of imatinib. CONCLUSION:
      Immunocell therapy may have a potent therapeutic effect when used in combination
      with molecularly-targeted therapy, which has few side-effects.

PMID- 15515426
TI  - Utilization of macrophages in anticancer therapy: the macrophage network theory.
AB  - Appropriate and rational modulation of innate immunity may enhance the
      therapeutic efficacy of emerging immune therapies for treating cancer. One of the
      crucial cells of innate immunity is the macrophage. The purpose of this article
      was to review those issues that suggest ways of exploiting macrophage local
      functions in immune therapy, and to discuss the suitability of low molecular
      weight lipopolysaccharides as potent modulators of macrophage functions for
      immune therapy of cancer.

PMID- 15515427
TI  - Immuno-cell therapy of cancer in Japan.
AB  - The immuno-cell therapy of cancer in Japan is in the phase of transition from
      therapeutic research to a more generalized option for all patients. A short
      history of cancer immunotherapy in Japan and its present status are summarized.
      In 1999, the first private clinic with a cell processing facility and
      specializing in immuno-cell therapy was established. Since then, the number of
      such clinics has increased. As a result, the number of patients who undergone the
      therapy has markedly increased. A summary of the clinical results of the therapy
      in 1401 patients treated in two leading clinics is also presented.

PMID- 15515428
TI  - Mature dendritic cells are superior to immature dendritic cells in expanding
      antigen-specific naive and memory CD8+ T cells.
AB  - BACKGROUND: For successful dendritic cell (DC)-based immunotherapy, it is
      critical to identify the most potent stage of human DCs, including immature DCs
      (imDCs) and mature DCs (mDCs). MATERIALS AND METHODS: imDCs were obtained by
      culturing monocytes in the presence of GM-CSF and IL-4 for 5- 7 days and imDCs
      were further cultured for 24-48 h in the presence of TNFalpha, IL-6, IL-1beta and
      PGE2 to obtain mDCs. Melan-A- and EBV (BRF1) peptides were used and the frequency
      of antigen-specific CD8+ T cells was assessed using appropriate tetramers.
      RESULTS: mDCs were potent antigen-presenting cells for the induction and
      proliferation of antigen-specific naive and memory CD8+ T cells and may overcome
      regulatory functions that suppress antigen-specific CD8+ T cells. CONCLUSION: Our
      findings that mDCs can efficiently expand antigen-specific naive and memory CD8 +
      T cells have important implications in the development of vaccination strategies
      and support the use of antigen-loaded mature DCs in human clinical trials

PMID- 15515429
TI  - Correlation of histological localization of tumor-associated macrophages with
      clinicopathological features in endometrial cancer.
AB  - BACKGROUND: To clarify the pathophysiological role of tumor-associated
      macrophages (TAMs), we performed clinicopathological analysis of CD68+ cells in
      70 cases of human endometrial cancer. MATERIALS AND METHODS: Using
      immunohistochemistry for CD68, we classified CD68+ cells into four groups: (a)
      those infiltrated into cancer cell nests or in close contact with cancer cells
      (nest TAM); (b) those in necrosis in the tumor center (hot-spot TAM); (c) those
      infiltrated into cancer stroma (stroma TAM); and (d) those distributed along the
      invasive margin of a tumor (Margin TAM). RESULTS: The aggregation of nest TAM
      related to high relapse-free survival rate after surgery. On the contrary,
      increased hot-spot TAM was a hazard to relapse-free survival and was
      proportionately-associated with clinical stage, myometrial invasion and
      histological differentiation. The extent of stroma TAM was associated with the
      presence of lymph node metastasis. CONCLUSION: Our findings demonstrate that the
      histological location of infiltrated TAMs may be taken into account in the
      clinical evaluation of endometrial cancer.

PMID- 15515430
TI  - Structural analysis of human specific cytolysin intermedilysin aiming application
      to cancer immunotherapy.
AB  - BACKGROUND: Intermedilysin (ILY) is a human specific cytolysin secreted by
      Streptococcus intermedius. In the present study, we performed molecular modeling
      of ILY and cholesterol-dependent cytolysins (CDCs) (pneumolysin, PLY;
      listeriolysin O, LLO; streptolysin O, SLO; alveolysin, ALV; suilysin, SLY;
      pyolysin, PLO) to compare the membrane binding domains including the
      undecapeptide (11mer) region which is thought to be necessary for the cytolytic
      activity of CDCs. MATERIALS AND METHODS: The molecular models of cytolysins were
      constructed using InsightII with Homology module with X-ray data of
      perfringolysin O (PFO). RESULTS: The ILY molecule was long and rod shaped, and
      comprised four domains. ILY was shown to possess stereocomplementary surfaces
      within the molecule and the potential to stack with 8 degrees of curvature
      leading to a ring cluster of 45 molecules or so in the human erythrocyte cell
      membranes. CONCLUSION: From the molecular orbital calculations and isostatic
      potential analysis, we considered that the ILY 11mer region has different
      features from those of traditional CDCs, and the ILY domain 4 should be very
      useful to apply the human cell-specific targeting module.

PMID- 15515431
TI  - Cloning and sequencing of variable region cDNAs of a novel human monoclonal
      antibody to carcinoembryonic antigen, and generation of a single chain variable
      fragmented antibody.
AB  - BACKGROUND: Taking into consideration immunogenicity in humans, human antibodies
      and their derivatives have potential advantages for cancer immunotherapy and/or
      gene therapy over those from different species such as mouse. Recently, we
      generated 22 human monoclonal antibodies (HmAbs) specific for human
      carcinoembryonic antigen (CEA) using KM mouse, which carries human antibody
      genes. In the present study, we tried to clone the variable (V) region genes of
      the C2-45 HmAb, with the highest affinity for CEA and to generate a human single
      chain variable fragmented (scFv) antibody. MATERIALS AND METHODS: Using RT-PCR
      methods, we cloned and sequenced cDNAs encoding V regions of C2-45, and
      constructed an scFv gene including a signal sequence for secreting into the
      periplasmic space of E. coli. RESULTS: Soluble scFv antibody, designated
      45KHscFv, was secreted in the periplasmic space and purified by Ni2+ affinity
      column from the supernatant of E. coli after osmotic shock. When analyzed by SDS
      PAGE, the 45KHscFv antibody showed a band corresponding to a calculated molecular
      weight of 30 kDa. The 45KHscFv antibody also retained a high reactivity with CEA
      in ELISA using immobilized CEA. CONCLUSION: These results indicate that the
      nonimmunogenic 45KHscFv antibody could be advantageously used for fusing with
      other human functional proteins such as cytokines.

PMID- 15515432
TI  - Association of the macrophage activating factor (MAF) precursor activity with
      polymorphism in vitamin D-binding protein.
AB  - BACKGROUND: Serum vitamin D-binding protein (Gc protein or DBP) is a highly
      expressed polymorphic protein, which is a precursor of the inflammation-primed
      macrophage activating factor, GcMAF, by a cascade of carbohydrate processing
      reactions. In order to elucidate the relationship between Gc polymorphism and
      GcMAF precursor activity, we estimated the phagocytic ability of three homotypes
      of Gc protein, Gc1F-1F, Gc1S-1S and Gc2-2, through processing of their
      carbohydrate moiety. MATERIALS AND METHODS: We performed Gc typing of human serum
      samples by isoelectric focusing (IEF). Gc protein from human serum was purified
      by affinity chromatography with 25-hydroxyvitamin D3-sepharose. A phagocytosis
      assay of Gc proteins, modified using beta-glycosidase and sialidase, was carried
      out. RESULTS: The Gc1F-1F phenotype was revealed to possess Galbeta1-4GalNAc
      linkage by the analysis of GcMAF precursor activity using beta1-4 linkage
      specific galactosidase from jack bean. The GcMAF precursor activity of the Gc1F
      1F phenotype was highest among three Gc homotypes. CONCLUSION: The Gc
      polymorphism and carbohydrate diversity of Gc protein are significant for its
      pleiotropic effects.

PMID- 15515434
TI  - Tumor-targeting of viral vectors for cancer gene therapy by using antibodies or
      their genes against tumor-associated antigens.
AB  - Gene therapy is a promising modality for the treatment of malignant tumors for
      which conventional therapies are often inadequate. Various therapeutic genes have
      shown promise for tumor cell killing. However, successful gene therapy depends on
      the development of efficient and targeted gene transfer vectors. The aim of this
      review is to summarize the tumor-targeting viral vectors for cancer gene therapy
      by utilizing antibodies or genes against tumor-associated antigens.

PMID- 15515433
TI  - A cell membrane modification technique using domain 4 of intermedilysin for
      immunotherapy against cancer.
AB  - Rapid cell membrane modification techniques are currently being sought in order
      to develop gene therapy and cellular immunotherapy modalities against cancer and
      other diseases. We developed a novel technique using the non-toxic portion of
      intermedilysin, a streptolysin O family cytolysin with a high affinity for human
      cell membranes, as a cell membrane adaptor module. Domain 4 recombinants of
      intermedilysin with linker sites at the N-terminus were designed. These modules
      are able to bind tightly to human cells after simple incubation and have no
      harmful effects. The modules were conjugated with the partially reduced or
      unreduced F(ab')2 of an anti-carcinoembryonic antigen monoclonal antibody.
      Erythrocytes bound to these conjugates were shown to specifically target a
      carcinoembryonic antigen-positive cell line, TT, in vitro. This is a promising
      technique for the development of convenient and effective anticancer treatment
      methods.

PMID- 15515435
TI  - Tumor cell-specific transcription of a murine histocompatibility class Ib Q5
      gene.
AB  - BACKGROUND: We previously reported that the Q5 gene product (Q5 antigen) was
      expressed on the surface of various tumor cells derived from H-2k (Qa-2-) mice.
      The Q5 antigen has tumor-protective antigenicity in the syngeneic mice. MATERIALS
      AND METHODS: Transcripts of the Qa region genes were analyzed by the RT-PCR
      method. Cell fractionation was performed with the MACS method and the phenotypes
      were estimated by flow cytometry analysis. RESULTS: Transcripts of Q5 were
      produced by all tumor cell lines. The Q5 transcription was detected only in
      thymocytes and PBMCs of H-2k (AKR and C3H/He) mice. The phenotype of the PBMCs in
      which Q5 transcription takes place seems to be, at least partly, CD3-48 cells
      that might be related to CD3-4-8- spontaneous thymoma cells derived from an H-2k
      mouse. CONCLUSION: The expression of Q5 in tumor cells in general is a result of
      a change of transcriptional regulation associated with malignant transformation.

PMID- 15515437
TI  - Long-term care for older adults: advocating for a new health-care paradigm.

PMID- 15515436
TI  - Detection of anti-HLA-F antibodies in sera from cancer patients.
AB  - BACKGROUND: We previously reported that a Q5 gene product (Q5 antigen) on the
      surface of tumor cells caused humoral immune reaction in syngeneic tumor-bearing
      mice. Transcripts of the Q5 gene were observed in various tumor cells. The human
      counterpart of the Q5 gene has not been clarified yet. MATERIALS AND METHODS:
      Transcripts of human class Ib genes in various human tumor cell lines were
      analyzed by the RT-PCR method. Whether anti-HLA-F antibodies were present in sera
      from cancer patients was investigated through Western blotting with recombinant
      HLA-F as an antigen. RESULTS: Transcripts of the HLA-F gene were produced by
      various tumor cell lines. In addition, anti-HLA-F IgG was present in the sera
      derived from various types of cancer patients (26 positives / 42 tested), but not
      in the sera derived from healthy donors (0 / 20). CONCLUSION: Anti-HLA-F
      antibodies should be further investigated as possible diagnostic tumor markers.

PMID- 15515439
TI  - The paired RAI/MDS specialist model. Improving outcomes in Veterans Affairs
      nursing home care units.

PMID- 15515440
TI  - Facilitating resident information seeking regarding meals in a special care unit:
      an environmental design intervention.
AB  - Repetitive questions and requests for information are common in older adults with
      dementia. The purpose of this environmental design intervention was to provide
      residents continuous access to information about common mealtime questions with
      the intent of decreasing agitation around mealtimes and facilitating more
      pleasant patient-staff and patient-patient interactions. A special care unit for
      residents with dementia of the Alzheimer's type was the setting. During the
      intervention conditions, a large clock and a sign with large lettering that
      identified mealtimes were hung in the dining area. Direct observations of 35
      residents were conducted at mealtimes for a 5-month period. Results showed
      reductions from baseline to the intervention phase in food-related questions or
      requests. These results suggest a simple, inexpensive environmental change
      intervention can reduce repetitive questions commonly exhibited by individuals
      with dementia.

PMID- 15515441
TI  - Enhancing communication with older adults: overcoming elderspeak.
AB  - Gerontological nurses promote health and successful aging for a growing
      population of older adults. Care providers unknowingly may communicate messages
      of dependence, incompetence, and control to older adults by using elderspeak, a
      speech style similar to baby talk, that fails to communicate appropriate respect.
      This article describes a communication training program that significantly
      reduced the use of elderspeak by nursing assistants and led t more respectful,
      less controlling, and equally as caring communication between nursing assistants
      and nursing home residents. Strategies to use in evaluating and enhancing
      interpersonal communication with older clients are provided. Therapeutic
      communication is a critical tool for nurses who provide health care to the
      growing populati of older adults.

PMID- 15515442
TI  - Moving to an assisted living facility: exploring the transitional experience of
      elderly individuals.
AB  - This qualitative study examined the effects of relocating to an assisted living
      facility in a select sample of elderly individuals. Small group interviews with
      open-ended discussion allow participants to express feelings about their
      transitional experi ence and recall situations in their adjustment process. Theme
      arising from the data included self-motivating factors, ties to the past,
      independence, affection, and adjustment, which co related with the principles of
      assisted living. This study revealed a beginning understanding of the experience
      of moving from a private home to assisted living and provided a framework for a
      new vision of these residents. Nursing implications are included that offer ways
      to provide assistance and further facilitate adjustment.

PMID- 15515443
TI  - Indoor gardening older adults: effects on socialization, activities of daily
      living, and loneliness.
AB  - This study examined the effects of indoor gardening on socialization, activities
      of daily living (ADLs), and perceptions of loneliness in elderly nursing home
      residents. A total of 66 residents from two nursing homes participated in this
      two-phase study. In phase one, experimental group 1 participated once a week for
      5 weeks in gardening activities while a control group received a 20-minute visit.
      While no significant differences were found between groups in socialization or
      perceptions of loneliness, there were significant pretest-posttest differences
      within groups on loneliness and guidance, reassurance of worth, social
      integration, and reliable alliance. The results also demonstrated gardening
      interventions had a significant effect on three ADLs (transfer, eating, and
      toileting). Phase two examined differences in the effects of a 5-week versus a 2
      week intervention program. Although no significant within-group differences were
      noted in socialization, loneliness, or ADLs, the 5-week program was more
      effective in increasing socialization and physical functioning.

PMID- 15515444
TI  - Aggression toward staff by nursing home residents: findings from a grounded
      theory study.
AB  - Aggressive behaviors by nursing home residents are common and can result in
      injury to both staff and residents. In addition, such aggressive behavior may
      lead to resident abuse by staff. This article describes a grounded theory study
      of nursing home staff response to aggressive residents and explores the problem
      of aggressive behaviors by nursing home residents, the conditions and context of
      aggression, and strategies staff use to prevent and manage aggression. To
      effectively deal with resident aggression, staff must become proactive, which
      involves three dynamic and interactive processes: practicing vigilance,
      intuiting, and strategizing. This article details these processes as well as the
      strategies staff use to deal with aggressive behaviors and makes specific
      recommendations for handling aggression toward staff.

PMID- 15515445
TI  - Return on investment in fund raising: using ROI to your advantage.

PMID- 15515446
TI  - Philanthropy--a board member's perspective.

PMID- 15515447
TI  - Foundations and health reform: meeting the challenge.

PMID- 15515448
TI  - A case study from Barlow Respiratory Hospital Foundation.

PMID- 15515449
TI  - Professional certification: assuring the public trust.

PMID- 15515450
TI  - Improving the performance of your board.
AB  - Leadership from your Board of Directors defines who you are as an organization
      and steers it, hopefully, in the proper direction. It takes an optimum balance of
      collective knowledge, skills, generations and geography to create a Board that
      will best suit your needs and those of your donors, patients and consumers.
      Leadership takes intelligence, character, integrity and energy. Getting the right
      volunteer leadership is one of our tougher challenges, and helping to improve
      their abilities and skills as Board members is even harder.

PMID- 15515452
TI  - End-of-life and palliative care: barriers, myths and misconceptions. Interview by
      Jane Robles.

PMID- 15515453
TI  - Transformation: the long reach of cancer.

PMID- 15515454
TI  - Bridge making. An oncology chaplain discusses her role in helping patients
      connect with others, a higher power--or even themselves.

PMID- 15515455
TI  - Practice development: what we learn with our British partners.

PMID- 15515456
TI  - [Chronic wounds in the era of evidence].

PMID- 15515457
TI  - ["Epicrisis method"--measurement of health care quality?].

PMID- 15515458
TI  - [Surgical treatment of hemorrhoids. Is stapling better than incision?].

PMID- 15515459
TI  - [Surgical treatment of hemorrhoids. An analysis of randomized trials published
      during the last five years].

PMID- 15515460
TI  - [Does incisional biopsy of a pigmented tumor increase the risk of metastasis if
      the tumor proves to be a malignant melanoma?].

PMID- 15515461
TI  - [Solarium use and melanoma risk].

PMID- 15515462
TI  - [Hormonal contraceptive patch].

PMID- 15515463
TI  - [Endoscopic ultrasound-guided biopsy in the mediastinum].

PMID- 15515464
TI  - [Pancreaticoduodenectomy in Denmark, 1996-2001].

PMID- 15515465
TI  - [Vaginal surgery in Denmark in 1999-2001. An analysis of operations performed,
      hospitalization and morbidity].

PMID- 15515466
TI  - [Should renal vein catheterization for selective renin determination be performed
      in patients with suspected renovascular hypertension?].

PMID- 15515467
TI  - [Clinical importance of neutralising antibodies against interferon-beta in
      patients with relapsing-remitting multiple sclerosis].

PMID- 15515468
TI  - [The long-term consequences of parental alcohol abuse: a cohort study of children
      in Denmark in 1966].

PMID- 15515469
TI  - [Unrecognised severe hypertension as a cause of failing eyesight in a 10-year-old
      boy].

PMID- 15515470
TI  - [Unilateral adrenalectomy as a treatment for serum ACTH-independent bilateral
      adrenal hyperplasia].

PMID- 15515471
TI  - [Continuity in health care].

PMID- 15515472
TI  - [Problematic report about recovered memories].

PMID- 15515473
TI  - [About the BOEL test].

PMID- 15515474
TI  - [Generic preparations, quality control and research].

PMID- 15515475
TI  - [Nothing wrong with generic preparations].

PMID- 15515476
TI  - [An open letter to the P.L.O. board].

PMID- 15515477
TI  - [Questions to the Attestudvalget concerning physicians' certification of patients
      work (in)capacity].

PMID- 15515478
TI  - [Metabolic syndrome--a high cardiovascular risk?].
AB  - Our knowledge about risk factors of atherosclerosis and their associations has
      considerably changed and improved. The importance of type 2 diabetes and
      hypertension was detected earlier, hyperlipidemia and dyslipidemia (disturbance
      of lipoprotein composition) have been recently implemented. We have learnt that
      the android obesity form and especially visceral fat serve as central trigger
      factor of the resulting "metabolic syndrome" and other related disturbances like
      acute phase proteins, inflammation markers and procoagulatory state. Altogether
      atherothrombotic events are increased and result in clinically relevant
      macrovascular disease (myocardial infarction, cerebrovascular und peripheral
      arterial disease), blood glucose itself causing additionally microvascular
      disease. The newest comprehensive guidelines of European Associations try to use
      most of the known factors for treatment guidelines but will fail due to the fact
      that they cannot be easily used in clinical practice. In additon, visceral fat,
      that central factor, and body fat mass have not been integrated. We suggest that
      the risk should be evaluated in the context of body mass index (BMI) and
      especially of waist circumference which could be THE central intervention factor
      in the treatment of our patients.

PMID- 15515479
TI  - Close association between parathyroid hormone and left ventricular function and
      structure in end-stage renal failure patients under maintenance hemodialysis.
AB  - BACKGROUND: Cardiovascular risk factors are a significant burden in end-stage
      renal disease patients under hemodialysis. Cardiovascular-related diseases are
      the leading cause of death among these patients and responsible for almost half
      of all deaths in dialysis patients. The influence of parathormone (PTH) on
      myocardial function as a toxin of uremia is attracting more attention and
      evaluation because of growing evidence that the effects of PTH on cardiac
      function may be the most serious consequence of secondary hyperparathyroidism in
      renal failure. In this study we aimed to consider the role of the excess PTH in
      the development of left ventricular hypertrophy (LVH) and its effects on LV
      ejection fraction in patients with end-stage renal disease under regular
      hemodialysis. METHODS: This cross-sectional study was done on patients with end
      stage renal disease (ESRD) undergoing maintenance hemodialysis treatment.
      Calcium, phosphorus, alkaline phosphatase and intact PTH (iPTH) were measured.
      Hypertensive patients were stratified into stages one to three. Echocardiography
      for left ventricular (LV) hypertrophy and ejection fraction (percent) were done
      and LV stratified into normal, mild, moderate and severe hypertrophy. RESULTS:
      The total number of patients was 73 (F = 28, M = 45), consisting of 58 non
      diabetic hemodialysis patients (F = 22, M = 36) and 15 diabetic hemodialysis
      patients (F = 6, M = 9). The age of patients was 46.5 +/- 16 years. The length of
      time patients had been on hemodialysis was 21.5 +/- 23.5 months. The LV ejection
      fraction (EF%) was 51 +/- 8 percent. Mean +/- SD of iPTH of total patients was
      309 +/- 349 pg/ml. Mean +/- SD of iPTH of diabetic group and non-diabetic group
      was 234 +/- 265 pg/ml and 329 +/- 368 pg/ml respectively. The value of serum
      alkaline phosphatase of total patients was also 413 +/- 348 IU/L. Serum alkaline
      phosphatase (ALP) of diabetic group and non-diabetic group was 295 +/- 179 IU/L
      and 443 +/- 375 IU/L respectively. Serum albumin of total patients was 4 +/- 0.75
      g/dl. Serum albumin of diabetic group and non-diabetic group was 3.6 +/- 0.7 g/dl
      and 4.2 +/- 0.7 g/dl respectively. Significant inverse correlation of serum ALP
      with percent of LV ejection fraction and marginal significant correlation of
      serum ALP with LVH were seen and marginal significant correlation of serum iPTH
      with LVH was also found. Significant inverse correlation between serum iPTH with
      percent of LV ejection fraction in non-diabetic HD patients was observed.
      CONCLUSIONS: Adverse effects of secondary hyperparathyroidism on LV function and
      structure in this study shows the role of excess PTH in the development of left
      ventricular hypertrophy as well as low LV ejection fraction. In patients with end
      stage renal disease under hemodialysis, more attention needs to be given to the
      control of secondary hyperparathyroidism to reduce the risk of cardiovascular
      morbidity and mortality in dialysis patients.

PMID- 15515480
TI  - Lipoprotein (a) in patients on hemodialysis.
AB  - Lipoprotein (a) [Lp(a)] may produce thrombogenic effects by modulating the
      fibrinolytic system. Elevated levels of Lp(a) have also been associated with an
      increased risk for atherosclerosis. Because atherosclerosis is more prevalent
      among patients with end-stage renal disease, the role of Lp(a) among patients on
      hemodialysis is analyzed. Twenty patients were studied. Lp(a) was measured before
      and after a hemodialysis session and before the following session. Between the
      first and second measures there was no statistical difference but when first and
      third measures were compared, a statistical difference (increase) was found. In
      conclusion, changes in Lp(a) levels were found and perhaps these changes are
      related to the episodic inflammation affecting patients on hemodialysis. The
      significance of these changes and the role in accelerating atherosclerosis in
      patients with end-stage renal disease are unknown.

PMID- 15515481
TI  - Urinary fluorine-18 fluorodeoxyglucose excretion with and without intravenous
      application of furosemide.
AB  - METHODS: Twenty patients suffering from malignancy received furosemide, twenty
      patients were examined by FDG-PET without diuretics. Urine volume and
      radioactivity were measured before and after acquisition. Bladder activity was
      evaluated qualitatively and quantitatively. RESULTS: Radioactivity in the bladder
      was lower and the image quality higher in the furosemide group. SUV values showed
      a median of 3.0 in the furosemide and 6.0 in the control group. With furosemide,
      a larger excreted volume was seen compared to the control group. The furosemide
      group showed a significantly higher ratio of excreted/ injected radioactivity
      early after injection. However, the totally excreted radioactivity was not
      significantly different (p = 0.93). CONCLUSION: Diuretics cause a higher urine
      volume with a diluted FDG concentration leading to an improved image quality.
      Furosemide accelerates early renal FDG elimination, reducing radiation exposure.

PMID- 15515482
TI  - Severe calcification in left main stem coronary artery stenosis visible on
      routine chest radiograph.
AB  - Coronary calcification is a strong predictor of significant coronary stenosis in
      symptomatic patients. While discrete calcification within coronary arteries is
      only detected by sensitive methods such as computed tomography, severe
      calcification can already be seen on the plain chest radiograph. In this article,
      we describe a patient with a high grade left main stem coronary artery stenosis
      who presented with a severe focal calcification on the plain chest radiograph in
      projection of the offspring of the left coronary artery.

PMID- 15515483
TI  - Breast cancer and concomitant primary hyperparathyroidism: description of two
      patients.
AB  - Breast cancer is the malignant neoplasm most commonly associated with
      hypercalcemia. In breast cancer the majority of the hypercalcemia cases result
      from osteolytic metastatic bone disease of the primary tumor. In a few patients
      hypercalcemia results from other conditions like primary hyperparathyroidism.
      Here, we present two female patients who were treated for breast cancer.
      Hypercalcemia in these two patients was diagnosed as being due to primary
      hyperparathyroidism. One of them was submitted to surgery and the calcium level
      dropped to the normal level thereafter. The other one refused surgery and was
      treated with biphosphonate and calcitonin. We suggest that when hypercalcemia
      occurs in breast cancer, primary hyperparathyroidism should be considered as
      possible cause.

PMID- 15515484
TI  - Two rare cases of the Pentalogy of Cantrell or its variants.
AB  - The Pentalogy of Cantrell (PC) is a rare association of defects involving the
      lower sternum, abdominal wall, diaphragm, pericardium and heart. We report two
      rare cases of the PC (variant form), showing fatal progression. Case 1 only
      survived two hours because of severe cardio-respiratory failure. Physical
      examination showed midline abdominal and thoracic defects, ectopic heart,
      pericardial defect, diaphragmatic defect, bilateral undescended testis,
      scoliosis, and adherence between left upper limb and trunk. In addition, the
      autopsy revealed diaphragmatic agenesia, intraabdominal testis, bilateral lung
      hypoplasia and lymphocytic meningitis. Case 2 only survived 15 minutes. In
      addition to the physical findings, including lower sternal defect, ectopic heart,
      epigastric omphalocele and scoliosis, the autopsy showed left diaphragmatic
      agenesia, pericardial agenesia, bilateral lung hypoplasia, deformed rib cage,
      anterior thoracic myeloschisis, adreno-hepatic fusion, left renal agenesia,
      meckel diverticulum and multiple accessory spleens. When comparing with other
      cases of PC, the concurrence of bilateral intraabdominal testis and lymphocytic
      meningitis in case 1, and adreno-hepatic fusion, anterior myeloschisis, meckel
      diverticulum, multiple accessory spleens, and renal agenesia in case 2 have not
      been described previously.

PMID- 15515485
TI  - Austrian syndrome--autopsy report.
AB  - A case of the Austrian syndrome in a 23 year-old male, alcoholic and non
      vaccinated against pneumococci, is reported. Autopsy study disclosed alcoholic
      liver disease, endocarditis, meningitis and pneumonia. Pneumococci were observed
      in the vegetations found in the mitral and aortic valves, in the coronarian
      septic embolus with acute myocardial infarction, and in the spleen abscess. The
      authors highlight the need for prevention measures against S. pneumoniae
      infection in alcoholics, suggesting that clinicians be alert to this infrequent
      but severe syndrome that bears Austrian's name.

PMID- 15515486
TI  - Sinusitis of odontogenic origin: pathophysiological implications of early
      treatment.
AB  - Although sinusitis is a common condition its pathogenesis is not clearly
      understood and there is lack of consensus concerning its treatment and
      prevention. Sinusitis is regarded as being primarily rhinogenous in origin, and
      oral/dental infections are considered to be predisposing factors. A review of the
      literature suggests that many cases of recurrent acute sinusitis are due to
      secondary rhinogenous bacterial colonization of antral mucosa that have been
      weakened and degenerated by chronic dental infection/inflammation. Unless the
      underlying dental condition, which may be asymptomatic or mildly symptomatic, is
      diagnosed and treated, the value of antibiotic treatment in such cases is
      questionable. In order to halt disease progression and avoid excessive antibiotic
      treatment, early intervention (both preventive and therapeutic) is necessary.
      Further research is required to establish the sequence of events by which
      infection of odontogenic origin initiates degenerative changes in the antral
      mucosa, culminating eventually in sinusitis.

PMID- 15515487
TI  - Laryngeal cancer in non-smoking and non-drinking patients.

PMID- 15515488
TI  - Direct measurement flow resistance of cochlear aqueduct in guinea pigs.
AB  - OBJECTIVE: The cochlear aqueduct connects the scala tympani to the subarachnoid
      space and is the main pressure equalization canal for the inner ear. Increases in
      inner ear volume and pressure are thought to cause clinical symptoms such as
      vertigo, tinnitus and fluctuating hearing loss. In this study the flow resistance
      of the cochlear aqueduct was determined and its relation with inner ear pressure
      was studied. MATERIAL AND METHODS: Inner ear pressure was measured in the scala
      tympani through the round window using a micropipette. Through a second
      micropipette, artificial perilymph was infused into, or withdrawn from, the scala
      tympani at various constant rates. From the infusion rate and the change in
      perilymphatic pressure during infusion the flow resistance of the cochlear
      aqueduct was calculated. RESULTS: The flow resistance was found not to be
      constant but to depend on the position of the round window membrane and possibly
      on the magnitude and direction of fluid flow through the aqueduct. Measured flow
      resistance values were in the range 11-45 Pa s/nl. For very small flow values the
      flow resistance averaged over 6 animals was 21 Pa s/nl. CONCLUSIONS: The flow
      resistance of the cochlear aqueduct is not a constant value. The cochlear
      aqueduct is a canal with dynamic properties and may play a role in the
      complicated process of inner ear pressure regulation.

PMID- 15515489
TI  - Effect of aminoglycoside otic drops on isolated cochlear outer hair cells with
      and without liver extract activation.
AB  - OBJECTIVE: To assess the ototoxicity of commercially available Gentacidin and
      TobraDex ear drops with and without liver extract activation using isolated
      cochlear outer hair cells (OHCs). MATERIAL AND METHODS: OHCs from adult
      chinchilla cochleae were exposed to standard bathing solution (SBS), liver
      extract alone and Gentacidin and TobraDex ear drops with and without liver
      extract. All experiments were performed at an osmolality of 305 +/-5 mOsm, at
      room temperature and for up to 60 min. OHC images were recorded using an inverted
      microscope and analyzed electronically. Time to cell death and changes in cell
      length were measured. RESULTS: The time to cell death and the percent change in
      cell length were significantly shorter in the Gentacidin+liver extract group than
      in the Gentacidin alone group (p < 0.05). The TobraDex+liver extract group showed
      a significantly decreased time to cell death compared to the SBS control group (p
      < 0.05). There were no significant differences in cell length or time to cell
      death between the TobraDex+liver extract group and the TobraDex alone group (p >
      0.05). CONCLUSION: This study suggests that the cytotoxicity of aminoglycoside
      ear drops to isolated OHCs in vitro requires

PMID- 15515490
TI  - Objective measurements of auditory nerve recovery function in nucleus CI 24
      implantees in relation to subjective preference of stimulation rate.
AB  - OBJECTIVE: Setting the optimal rate of stimulation for individual cochlear
      implant recipients is critical to the successful functional outcome of cochlear
      implantation. In the absence of an objective methodology, cochlear implants are
      currently fitted by means of a time-consuming (and therefore expensive) trial-and
      error process of limited accuracy. The aim of this study was to evaluate a
      possible relationship between the patient's subjectively preferred stimulation
      rate and an objective measurement of auditory nerve recovery time. MATERIAL AND
      METHODS: Eleven recipients of Nucleus CI 24 implants initially fitted with a
      speech processor using the ACE speech-coding strategy at a rate of 900 Hz were
      introduced to 2 other stimulation rate options, 1200 and 1800 Hz, at 2 different
      fitting sessions and asked to choose their preferred rate. Preferences were
      compared with objective measurements of auditory nerve recovery time obtained
      using the refractory recovery function of neural response telemetry. RESULTS: The
      auditory nerve recovery time for individuals with a subjective preference for a
      slow stimulation rate was longer than that for individuals who preferred a fast
      stimulation rate, with significant differences between the 2 groups for 3 tested
      electrodes (7, 11 and 15): p = 0.024, 0.009 and 0.03, respectively (Mann-Whitney
      test). CONCLUSION: The association observed between the subjective stimulation
      rate preference and measurements of auditory nerve recovery time indicates that
      the measured auditory nerve recovery time can be used as a reliable predictor for
      setting up a basic stimulation rate of a particular individual's map, thus
      reducing the cost of the technology and significantly increasing its
      effectiveness.

PMID- 15515491
TI  - Imagination of body rotation can induce eye movements.
AB  - OBJECTIVE: Several studies have shown that spatiotemporal aspects of motion are
      stored and can be retrieved with the use of vestibular and somatosensory cues.
      The purpose of this study was to examine whether intentional imagination of body
      rotation can induce oculomotor activity similar to the typical vestibulo-ocular
      reflex (VOR). MATERIAL AND METHODS: Normal subjects without known vestibular
      and/or oculometric abnormalities were instructed to imagine a sensation of
      accelerating body rotation in the horizontal plane (rightward or leftward) while
      sitting in darkness with closed eyes, using only vestibular and somatosensory
      cues and not imaginary visual cues. Eye movements were recorded during the
      imagery session and also during a full, routine electronystagmography (ENG) test.
      All subjects selected for this study showed normal results in the ENG test, and
      none of them had gaze-evoked or end-point nystagmus. RESULTS: In response to
      imaginary rotations, horizontal eye movements were found in 91/121 recordings
      (75%) in 10 subjects. A typical pattern of nystagmus (0.3-3 Hz, 3-30 degrees /s
      maximal speed of slow component) was recorded in 53% of mental rightward
      rotations and 49% of leftward rotations. The fast component was always in the
      direction of the imaginary rotation (similar to a normal VOR). Other types of eye
      movement comprised either contralateral eye drift ( approximately 17% of trials)
      or macro square waves. In 25% of the recordings no definite eye movements could
      be detected during the mental maneuvers. CONCLUSION: These mentally induced eye
      movements seem to be due to a cortical process which can affect the normal input
      to the brainstem nuclei. A possible mechanism is discussed. This phenomenon may
      serve as an objective measurement of mental activity, may be used for testing the
      cognitive resources of patients and can probably be used for enhancing the
      rehabilitation process after acute vestibular insult.

PMID- 15515492
TI  - Habituation to galvanic vestibular stimulation for analysis of susceptibility to
      carsickness.
AB  - OBJECTIVE: In a previous study we developed a standardized procedure for a
      reproducible quantification of galvanic-induced body sway (GBS). In line with
      other reports, GBS shows short-term (fast) habituation upon stimulus repetition.
      The aim of this study was to evaluate whether the degree of short-term
      habituation to galvanic vestibular stimulation (GVS) is correlated with
      susceptibility to carsickness. MATERIAL AND METHODS: A total of 24 female
      subjects underwent computer-controlled GVS as part of a prospective experimental
      study conducted in a tertiary referral center. A binaural 1-cosinusoidal stimulus
      of 0.5 Hz and 1 mA was repeated five times. Binaural stimulation was chosen to
      obtain maximum responses, making possible habituation to repetitive GVS obvious.
      The groups consisted of 12 subjects suffering from carsickness and 12 healthy
      subjects. RESULTS: Analysis of the repeated measurements test showed that the GBS
      gain curve for the carsickness group was always superimposed on that for the
      healthy subjects. However, the (absolute) first to fifth GBS gains showed no
      significant differences (p = 0.134 - 0.995). When comparing short-term
      habituation in subjects suffering from carsickness versus healthy subjects, the
      results showed no differences in the mean values of the first (30.534% vs
      27.024%), final (42.637% vs 38.544%) and average (35.544% vs 33.644%)
      habituations (p = 0.875, 0.991 and 0.951, respectively). CONCLUSION: We did not
      observe any significant differences in sensitivity or habituation of the GBS in
      carsick subjects compared to healthy subjects. This implies that carsick subjects
      show a similar ability to discard an irrelevant, non-motion sickness-inducing
      galvanic stimulus as healthy subjects.

PMID- 15515493
TI  - Role of auditory stimulation in maturation of the auditory pathway.
AB  - OBJECTIVE: To compare the maturation of the auditory pathway, as shown by
      electrical brainstem auditory potentials (EABRs), in ears with and without prior
      auditory stimulation. MATERIAL AND METHODS: Electrophysiological data were
      collected prospectively from ears which had received cochlear implants. Implant
      evoked (Imp)EABRs were recorded. Thirty children, implanted after January 2000,
      were selected according to a strict inclusion/exclusion protocol. All the
      children had received a 22-channel Nucleus cochlear implant (CI24 series).
      Intraoperatively, ImpEABRs were recorded using the Medelec Synergy Evoked
      Response system in conjunction with Nucleus Neural Response Telemetry software.
      The ImpEABR latencies of waves eII, eIII and eV and the morphology of wave eV
      were assessed. RESULTS: ImpEABRs alter during the first 12 months of life. The
      latency becomes shorter during this period and the morphology of wave eV alters
      from a broad shape to a more distinct waveform. This appears to occur
      independently, even in the absence of auditory stimulation. CONCLUSION: The
      development of electrical brainstem auditory potentials is not dependent on
      auditory stimulation.

PMID- 15515494
TI  - Dynamic posture assessment in patients with peripheral vestibulopathy.
AB  - OBJECTIVE: To assess the effects on balance of different strategies to create
      sensory conflict. MATERIAL AND METHODS: Two different systems of dynamic
      posturography were compared: computerized dynamic posturography and a static
      platform on which different visual and support conditions were used. The study
      was performed in 127 patients with dizziness of a peripheral vestibular origin.
      RESULTS: When patients stood on a foam support surface, the length and area of
      the center-of-pressure excursions increased. Interestingly, optokinetic
      stimulation evoked a longer length and a wider area of the center-of-pressure
      excursions in patients with a combined vestibular and visual deficit pattern than
      when they kept their eyes closed. This was opposite to the effect observed in
      patients with a pattern indicative of a vestibular deficit alone. CONCLUSION: The
      effects of visual stimulation on balance in patients with unilateral
      vestibulopathy reflect the type of sensory deficit, and can be considered to be
      specific to such a deficit.

PMID- 15515495
TI  - Immunohistochemical demonstration and semi-quantitation of vascular endothelial
      growth factor in recurrent versus non-recurrent nasal polyps.
AB  - OBJECTIVE: The expression of some growth factors in nasal polyps has been
      examined, although investigations addressing the reason for recurrence in some
      patients are lacking. Vascular endothelial growth factor (VEGF) is expressed by
      inflammatory cells, as well as by endothelial and epithelial cells of nasal
      polyps. To determine whether VEGF may play a role in the recurrence of nasal
      polyps, we aimed to compare VEGF expression in recurrent versus non-recurrent
      polyps. In addition, expression in polyps from asthmatic patients was compared
      with that in polyps from non-asthmatics. MATERIAL AND METHODS: A total of 30
      patients with newly diagnosed nasal polyposis were included. Polypectomy was
      performed at enrolment in the long-term follow-up study. Fifteen patients had
      only 1 polypectomy (non-recurrence group; median observation period 81 months)
      and 15 had a median of 6.4 polypectomies (multiple recurrence group; median
      observation period 108 months). Five of 10 patients with asthma belonged to the
      non-recurrence group and 5 to the recurrence group. The polyp obtained at the
      initial polypectomy was examined for expression of VEGF by immunohistochemistry,
      using a polyclonal antibody. A blinded semi-quantitation and comparison of the
      intensity of immunolabelling were performed in recurrent versus non-recurrent
      polyps, as well as in asthmatics versus non-asthmatics. RESULTS: VEGF expression
      was seen as varying staining of the polyp surface and gland epithelium, as well
      as of the vessel endothelium and some stromal mono- and polymorphonuclear
      leukocytes. Semi-quantitation of the staining intensity showed no significant
      differences between recurrent and non-recurrent polyps, or between asthmatics and
      non-asthmatics. CONCLUSION: Our findings indicate that the level of
      immunohistochemical expression of VEGF in recurrent and nonrecurrent nasal
      polyposis is equivalent. Thus, the level of VEGF expression cannot predict a
      subsequent recurrence. The expression of VEGF is not upregulated in patients with
      asthma. Further studies are needed to determine the role of VEGF in nasal
      polyposis, with special reference to different stages of polyp formation,
      vascularization and growth.

PMID- 15515496
TI  - DNA ploidy, S-phase fraction and associations with 2-18F-fluoro-deoxy-2-D-glucose
      positron emission tomography findings before and during therapy of head and neck
      squamous cell carcinoma.
AB  - OBJECTIVES: The main purpose of this study was to investigate the feasibility of
      fine needle aspiration (FNA) of neck node metastases in head and neck squamous
      cell carcinoma (HNSCC) for evaluating changes in DNA ploidy and S-phase fraction
      (SPF) during cytotoxic treatment. The results of flow cytometric (FCM) and image
      cytometric (ICM) analyses of ploidy were compared. Secondly, the association of
      SPF and ploidy with the metabolic rate (MR) of 2-18F-fluoro-deoxy-2-D-glucose
      (FDG) in positron emission tomography (PET) was studied. MATERIAL AND METHODS:
      Between 1993 and 1999, 47 patients with locally advanced, non-resectable HNSCC
      underwent FDG PET prior to (PET1) and early during (PET2) cytotoxic radical
      treatment. The MR of FDG was calculated separately in primary tumours and lymph
      node metastases. Immediately after both PET scans, FNA of node metastases was
      done in 29 patients at PET1 and in 27 at PET2. DNA ploidy was evaluated using FCM
      and manually using ICM. The SPF was evaluated using FCM only. RESULTS: At PET1 it
      was possible to evaluate the SPF using FCM in only 13/29 aspirations due to a
      poor cell yield or large amounts of debris. Ploidy was obtained in 23/29
      aspirates using FCM and in 27/29 using ICM. A discordance in ploidy findings was
      apparent, with more non-diploid clones being detected by ICM than FCM.
      Eradication of non-diploid clones during therapy was observed in six cases using
      FCM, of which only one was confirmed by ICM. Neither SPF nor ploidy status showed
      any strong correlation with the MR of FDG. CONCLUSION: FNA of HNSCC metastases
      demands a high and qualitatively good cell yield for FCM examinations. ICM is
      laborious but feasible and offers more accurate detection of non-diploid cell
      clones. Ploidy and SPF were not strongly associated with FDG metabolism.

PMID- 15515497
TI  - Cough induced by mechanical stimulation of the upper airway in humans.
AB  - OBJECTIVES: Cough has previously been induced in animals by means of mechanical
      stimulation of the upper airway but this method has not previously been applied
      to humans. The aims of this study were to determine if cough could be induced in
      humans on mechanical stimulation of the upper airway and to see if this
      mechanically induced cough was reproducible. We also wished to investigate if
      there was any difference in cough sensitivity between healthy subjects and those
      with acute upper respiratory tract infection (URTI). MATERIAL AND METHODS: In the
      first investigation, 2 groups were studied: 15 healthy subjects and 30 subjects
      with URTI with a mean age of 20 years. Cough was induced by vibration of the
      airway at the level of the trachea using a modified men's shaver. In the second
      investigation to determine the reproducibility of this mechanically induced
      cough, two groups from a different population were studied: 15 healthy subjects
      and 29 subjects with URTI with a mean age of 20.3 years. Cough was induced by
      airway vibration before and after a 90-min rest period. RESULTS: In the first
      investigation it was demonstrated that cough can be induced within 2 s of
      vibration; subjects with URTI are more sensitive to cough induction and cough
      approximately five times more than healthy subjects; cough increases with
      repeated stimulation and reaches a maximum after three periods of vibration; the
      cough response may be mediated by rapidly adapting airway sensory receptors. In
      the second investigation there was no significant difference in mean cough counts
      before and after a 90-min rest period in both groups, which demonstrates that the
      mechanically induced cough is reproducible. CONCLUSION: This is the first study
      to elicit cough in humans by mechanical stimulation of the upper airway. This new
      method of inducing cough in subjects with URTI may be useful for studying both
      the mechanism of cough and the effects of antitussive medicines.

PMID- 15515498
TI  - Prevention of biofilm formation by dairy products and N-acetylcysteine on voice
      prostheses in an artificial throat.
AB  - OBJECTIVE: To evaluate the preventive effect of buttermilk, Yakult Light
      fermented milk drink and N-acetylcysteine on biofilm formation on voice
      prostheses in vitro. MATERIAL AND METHODS: Groningen button and Provox 2 voice
      prostheses were inoculated with a mixture of bacteria and yeasts isolated from
      previously explanted Groningen button voice prostheses. After 5 h, separate
      throats were flushed with buttermilk, Yakult Light fermented milk drink, N
      acetylcysteine or phosphate-buffered saline, which served as a control. After 7
      days, the microflora on each voice prosthesis was determined. RESULTS: On
      Groningen button voice prostheses, buttermilk, Yakult Light fermented milk drink
      and N-acetylcysteine all reduced the amount of both bacteria and yeasts. On
      Provox 2 voice prostheses, buttermilk, Yakult Light fermented milk drink and N
      acetylcysteine reduced the amount of bacteria but, conversely, increased the
      amount of yeasts. CONCLUSION: These in vitro experiments demonstrate that biofilm
      formation on voice prostheses is reduced in an artificial throat by the use of
      buttermilk, Yakult Light fermented milk drink and N-acetylcysteine. However, the
      structural differences between the type of voice prostheses may influence the
      ultimate effects.

PMID- 15515499
TI  - Thyroplasty type I without arytenoid adduction in patients with unilateral
      laryngeal nerve paralysis: the montgomery implant versus the Gore-Tex implant.
AB  - OBJECTIVE: The current series was designed to compare the results achieved with
      the Montgomery and Gore-Tex implants in thyroplasty type I without arytenoid
      adduction in patients with unilateral laryngeal nerve paralysis. MATERIAL AND
      METHODS: An inception cohort of 57 French language speakers with unilateral
      laryngeal nerve paralysis were managed with thyroplasty type I using Gore-Tex
      (Group GT; n = 24) or Montgomery (Group M; n = 33) implants. The two groups had
      similar patient characteristics. Morbidity, phonatory results according to self
      assessment by the patient and selected speech and voice parameters (fundamental
      frequency, jitter, shimmer, noise:harmonic ratio, phonation time, phrase grouping
      and speech rate) were analyzed 1 month postoperatively in both groups. RESULTS:
      Dyspnea, as noted in three patients, was the only immediate complication. Late
      complications included persistent inflammation of the vocal cord after insertion
      of a Gore-Tex implant, endolaryngeal extrusion of the Gore-Tex implant and
      dislodgment of the Montgomery implant in one patient each. Postoperatively, all
      patients reported improvements in speech and voice. Secondary degradation of
      speech and voice was noted in one patient in each group. Comparison of selected
      speech and voice parameters at 1 month postoperatively showed (i) a statistically
      significant (p < 0.01) decrease in the jitter, shimmer and noise:harmonic ratio
      values and (ii) a statistically significant (p < 0.01) increase in the speech
      rate values in Group M compared to Group GT patients. Also, a trend (0.05 <p <
      0.1) was noted towards an increase in the phrase grouping values in Group M
      compared to Group GT patients. CONCLUSIONS: Although limitations exist in the
      interpretation of the reported data, our results suggest that in patients with
      unilateral laryngeal nerve paralysis managed with a thyroplasty type I technique
      without arytenoid adduction, the use of a Montgomery compared to a Gore-Tex
      implant does not influence the success of the procedure according to the
      patient's self evaluation or the morbidity but does lead to a significant
      improvement in the values of selected speech and voice parameters.

PMID- 15515501
TI  - Ulcerating Warthin's tumour.
AB  - We report the clinical course of a 63-year-old man with a Warthin's tumour in the
      right parotid gland that had ulcerated the overlying skin. The ulceration may
      have been due to the malignant transformation of either the epithelial or
      lymphoid component or, as in very rare cases, it may have resulted from
      inflammatory alterations crossing the capsule of the tumour into the adjacent
      parotid parenchyma and surrounding skin. Only two similar cases of the latter
      have been reported to date. The main clinical pitfall of such an inflammatory
      skin disruption of an otherwise benign Warthin's tumour is that it may be
      mistaken for an infiltratively growing malignant lesion.

PMID- 15515500
TI  - Outcome of surgical management of laryngeal carcinoma: a 5-year experience.
AB  - OBJECTIVE: To investigate the outcome of surgically managed laryngeal carcinoma
      patients attending an outpatient clinic over a 5-year period. MATERIAL AND
      METHODS: This was an analytical, retrospective, cross-sectional study. A total of
      36 laryngeal carcinoma patients who were managed surgically with or without
      radiotherapy were analyzed. RESULTS: A total of 32 patients (89%) were found to
      be disease-free during follow-up for up to 5 years. Two patients (5.5%) died
      because of intercurrent infection and recurrence of the disease and two (5.5%)
      were lost to follow-up 5 and 7 months after surgery, respectively. CONCLUSIONS:
      The results indicate that the best disease-free rates can be achieved by managing
      laryngeal carcinoma surgically with or without radiotherapy depending on the
      advancement and aggressiveness of the disease.

PMID- 15515502
TI  - Solitary extramedullary plasmacytoma arising in the pterygoid fossa.
AB  - A case of solitary extramedullary plasmacytoma of the left pterygoid fossa is
      presented, which is an unusual location for such tumors. A 54-year-old male
      patient was admitted for retro-orbital and left-sided facial pain which had
      persisted for several months. Physical, nasal endoscopic and optic examinations
      showed no abnormalities. No palpable cervical lymph nodes were found. MRI
      revealed a 2-cm mass in the left pterygoid fossa. A biopsy was carried out and
      the resulting histological evaluation of the mass confirmed a plasmacytoma. A
      comprehensive work-up, including bone marrow biopsy, total-body skeletal survey,
      technetium scintigrams, determination of urine Bence-Jones protein and serum
      myeloma protein, chest radiograph, total blood count and urinalysis, was carried
      out in order to rule out multiple myeloma. All of these studies were unremarkable
      in terms of a systemic disease and therefore the patient was diagnosed as having
      a solitary extramedullary plasmacytoma of the pterygoid fossa. He was referred
      for radiation therapy, receiving irradiation of 50 Gy for 6 weeks. The clinical
      manifestations, imaging findings, pathology and treatment procedures of
      extramedullary plasmacytoma are described, together with a review of the
      literature.

PMID- 15515503
TI  - Recurrent extracranial sinonasal meningioma presenting 27 years after complete
      surgical eradication of right frontal meningioma.
AB  - A 79-year-old man presented to our department with nasal obstruction and
      postnasal drip. On examination he had unusual bilateral nasal polyps, which were
      histologically diagnosed as meningioma. Twenty-seven years earlier he had
      undergone successful removal of a right frontal meningioma. A CT scan performed 7
      years after his primary surgery had shown complete excision with no evidence of
      recurrence. Extracranial meningiomas are rare tumours and are usually extensions
      from an intracranial mass lesion. We document what we believe to be the first
      case of an extracranial meningioma, presenting as nasal polyps, 27 years after
      successful surgical eradication of the primary lesion.

PMID- 15515504
TI  - Carcinoid tumor of the middle ear.
AB  - Although carcinoid tumors are labeled as neuroendocrine tumors they can also
      originate in tissue lacking neuroendocrine cells, such as that in the middle ear.
      Symptoms of a carcinoid tumor in the middle ear are common ear symptoms such as
      fullness, pain and hearing loss. Carcinoid tumors have also been considered to be
      slow-growing. Both these aspects can easily lead to a relatively late diagnosis
      of carcinoid tumor of the middle ear. The diagnosis is made histologically, and
      the tumor is primarily treated surgically. In the follow-up of patients,
      octreotide scanning has proved to be a sensitive method in cases of both
      recurrence and metastasis. Our patient was a 34-year-old, otherwise healthy
      female with left-sided acute otitis media and facial palsy in her left ear. She
      had also suffered from the same symptoms 4 years earlier. She was treated with an
      operation, and the histologic diagnosis was a carcinoid tumor. In the follow-up
      of the patient we used octreotide scanning.

PMID- 15515505
TI  - Role of open incisional biopsy in parotid tumors.
AB  - OBJECTIVE: Parotid gland enlargement due to diffuse pathologic processes
      represents a diagnostic challenge for the surgeon. In such cases, fine-needle
      aspiration is inconclusive and superficial parotidectomy is usually performed.
      MATERIAL AND METHODS: The authors treated eight patients who underwent open
      incisional biopsy of the parotid gland with continuous monitoring of the facial
      nerve. RESULTS: In all cases, fine-needle aspiration cytology did not provide a
      definitive diagnosis while open incisional biopsy provided an accurate diagnosis
      of a lymphoproliferative disorder, with no operative complications. CONCLUSION:
      In certain infiltrative parotid diseases such as lymphoepithelial or
      lymphoproliferative diseases, when fine-needle aspiration biopsy is insufficient
      as tissue architecture is an important component of the pathological diagnosis,
      an open incisional biopsy can be considered. This procedure can provide an
      accurate histological diagnosis while avoiding superficial parotidectomy.

PMID- 15515506
TI  - Syringocystoadenoma papilliferum of the external ear canal: an
      immunohistochemical study.

PMID- 15515507
TI  - Magnetic resonance imaging of the shoulder.

PMID- 15515508
TI  - Alveolar echinococcosis of the liver: correlative color Doppler US, CT, and MRI
      study.
AB  - PURPOSE: To determine and compare the imaging features of hepatic alveolar
      Echinococcosis using color Doppler US, CT, and MRI. MATERIAL AND METHODS:
      Abdominal CT and MRI with and without contrast agents and color Doppler US were
      performed on seven patients with hepatic alveolar Echinococcosis. The lesions
      were evaluated for location, features of echogenicity, intensity and density,
      calcification, and vascular, hilar, and perihepatic involvement. The diagnosis
      was confirmed histopathologically in all patients. RESULTS: Six patients had
      solitary lesions, and one displayed multiple lesions. The lesions were generally
      seen as heterogeneous and hyper- or hypoechoic when imaged with color Doppler US,
      hypodense with CT, and hypointense with MRI, in comparison with the liver
      parenchyma. Calcification, central necrosis, and small peripheral cysts were
      observed in six, seven, and four patients, respectively. Vascular flow or
      contrast enhancement was not observed in any of the cases. A look at the
      respective advantages of each method reveals that calcification was best rendered
      visible via CT, small peripheral cysts with T2-weighted MRI, central necrosis
      with CT and MRI, and perihepatic invasion with multiplanar MRI. Vascular
      involvement was revealed by all methods. CONCLUSION: Color Doppler US, CT, and MR
      imaging function extremely well as complementary methods in the diagnosis of HAE.
      Color Doppler US should be performed in these patients owing to its ability to
      efficiently detect the disease. Knowledge of imaging characteristics makes it
      possible to radiologically ascertain an early diagnosis.

PMID- 15515509
TI  - Unusual enhancement pattern of liver lesions in hepatosplenic candidiasis.
AB  - PURPOSE: To describe an unusual enhancement pattern of hepatosplenic candidiasis
      (HSC) liver lesions in biphasic spiral liver computed tomography (CT). MATERIAL
      AND METHODS: Twenty-one patients with suspected HSC were scanned with a biphasic
      liver CT perfusion protocol. The liver lesions detected were assessed for their
      morphology and enhancement pattern during both perfusion phases. A liver biopsy
      was performed in 11/21 patients. RESULTS: The majority of hepatic lesions in
      15/21 patients showed the well-known abscess-like pattern. In 6/21 patients an
      uncommon central contrast enhancement with a peripheral double ring was detected
      in the arterial phase. In some cases the lesions showed decreased diameter or
      even seemed to disappear completely in the portalvenous phase. CONCLUSIONS: CT in
      the arterial phase showed an unusual enhancement pattern of liver lesions in HSC.
      Scanning only in the portalvenous phase implies possible pitfalls, because
      lesions may be overlooked or undersized. Therefore, biphasic liver CT is
      considered essential in the diagnosis and follow-up of HSC in clinical practice.

PMID- 15515510
TI  - Biochemical and cytologic analysis of cystic contents in benign non-parasitic
      symptomatic hepatic cysts before and after ethanol sclerotherapy.
AB  - PURPOSE: To examine the fluid of liver cysts by cytologic and biochemical
      analysis before and after ethanol sclerotherapy in order to explore the etiology
      of cystic fluid reproduction after sclerotherapy. MATERIAL AND METHODS: The
      contents of 11 cysts in 11 patients were examined on the day of sclerotherapy,
      and 2-8 (mean 4.5) days later, and analysed for cytologic and biochemical
      parameters. RESULTS: Cytologic signs of acute or subacute inflammatory reaction
      were absent before and present in all cysts after sclerotherapy. Biochemical
      parameters reflecting the acute inflammatory reaction (CRP, orosomucoid and
      haptoglobine), changes in capillary permeability (protein, albumin), and the
      cystic epithelial function (bilirubin, alkaline phosphatase) were significantly
      elevated after sclerotherapy. CONCLUSION: The post-sclerotherapy fluid production
      is probably due to an inflammatory reaction. This may explain the success of
      performing sclerotherapy in one single session.

PMID- 15515511
TI  - Cuff-compression of the proximal calf to reduce venous contamination in contrast
      enhanced stepping-table magnetic Resonance angiography.
AB  - PURPOSE: To minimize venous overlay at the calf station in contrast-enhanced
      three-dimensional (3D) stepping-table magnetic resonance angiography (MRA) using
      a continuous cuff-compression technique during MR data acquisition. MATERIAL AND
      METHODS: Within 14 months, 32 patients suffering from symptomatic peripheral
      arterial occlusive disease (PAOD) with a bilateral ankle-brachial index (ABI) of
      0.8 or below were consecutively enrolled in this study. Unilateral cuff
      compression of the proximal calf was applied in the study group (n = 14). The
      control group (n = 18) underwent no compression. All patients underwent three
      step 3D contrast-enhanced magnetic resonance angiography (3D CE-MRA) according to
      the institute's protocol. Venous contamination scores (vcs) at the calf station
      were blindly ranked by a 1 to 3 rating score (3 = major venous contamination).
      The vcs values of the control group were regarded as standard. Statistical
      significance between both groups was evaluated with a paired t test. RESULTS:
      Symmetric venous contamination was observed within the control group with a mean
      vcs of 2.2+/-0.6 on the left side and 2.2+/-0.7 on the right side with
      deltavcsleft-right of 0.1+/-0.2 (P>0.1). In the study group, asymmetric venous
      contamination was determined with vcsmean = 2.3+/-0.6 for the uncompressed side
      and vcsmean =1.4+/-0.5 for the compressed side and a deltavcsuncomp-comp of 0.9+/
      0.5 (P<0.00005). The control group and the uncompressed side of the study group
      showed no significant difference in venous contamination (P > 0.1). CONCLUSION:
      Subdiastolic cuff-compression of the proximal calf is an easily applicable and
      inexpensive technique by which to reduce venous contamination of the calf station
      in stepping-table MR angiography and to improve evaluation of the infrapopliteal
      arteries.

PMID- 15515512
TI  - An asymptomatic pulmonary hilar mass: a case report.
AB  - Pulmonary vein varix is a rare benign abnormality, either congenital or acquired,
      usually presented without symptoms. It is most frequently discovered by chance on
      a chest radiograph, whereas computed tomography defines the special
      characteristics of the lesion. Angiography is considered the method of choice for
      final diagnosis. The authors present the first case of a patient with pulmonary
      vein varix accompanied by interatrial communication.

PMID- 15515513
TI  - Complications following ultrasound-guided thoracocentesis.
AB  - PURPOSE: To retrospectively register the number and type of complications
      following ultrasound-guided thoracocentesis, and to evaluate the need for routine
      chest X-ray after the procedure. MATERIAL AND METHODS: Complications were
      retrospectively registered from the radiological and clinical reports of 371
      consecutive patients who had undergone thoracocentesis with a total of 711
      procedures. RESULTS: The mean volume evacuated was 823ml (range 0-3600ml). Twenty
      (2.8%) pneumothoraces were found after 711 thoracocenteses, but in no case was
      chest tube drainage necessary. Hemoptysis occurred in one patient. CONCLUSION:
      Ultrasound-guided thoracocentesis was found to be a safe procedure. Based on
      these results, no reason was found to introduce an upper limit of the amount of
      fluid drained in one session. Routine follow-up chest X-ray is not justified in
      the absence of clinical symptoms.

PMID- 15515514
TI  - Myositis ossificans of psoas muscle: magnetic resonance imaging findings.
AB  - Myositis ossificans is a benign, localized, self-limiting ossifying soft tissue
      mass with unknown pathogenesis. It may be confused with a malignant tumor of bone
      or soft tissues, especially in the early stages of the disease. In this report,
      we present a case of myositis ossificans affecting unilateral psoas muscle, which
      to our knowledge is a very uncommon location. There was no history of trauma. We
      describe the imaging findings and clues to early diagnosis of myositis
      ossificans.

PMID- 15515515
TI  - Long-term MRI findings in operated rotator cuff tear.
AB  - PURPOSE: To describe magnetic resonance imaging (MRI) findings at long-term
      follow-up after rotator cuff (RC) tear using standard MRI sequences without fat
      saturation. MATERIAL AND METHODS: Twenty-eight patients aged 55.8+/-7.6 underwent
      MRI examination 4.6+/-2.1 years after surgery for RC tear. Standard sequences in
      oblique coronal, oblique sagittal, and axial planes were obtained. The RC,
      including re-tears and tendon degeneration, was independently evaluated by two
      observers. Thickness of the supraspinatus tendon and narrowing of the subacromial
      space were measured. The clinical outcome was evaluated with the Constant score
      and compared with the MRI findings. RESULTS: The RC tear was traumatic in 18
      (64%) patients and degenerative in 10 (36%). At follow-up, 11 (39%) had normal RC
      tendons with good clinical outcome. Four (14%) patients had painful tendinosis
      without RC tear. A full-thickness RC tear was found in 7 (25%) patients and a
      partial tear in 6 (21%). In one patient with a full-thickness tear, and in two
      with partial tear, tendinosis was found in another of the RC tendons. The
      subacromial space was narrowed in 13 (46%) of the patients. A narrowing of the
      subacromial space correlated with re-tear (P<0.05). CONCLUSIONS: The RC may be
      evaluated with standard MRI sequences without fat saturation at long-term follow
      up. A normal appearance of the RC is correlated with good clinical outcome, while
      re-tear and tendinosis are associated with pain.

PMID- 15515516
TI  - Whole body magnetic resonance imaging in the diagnosis of Parsonage Turner
      syndrome.
AB  - PURPOSE: To describe magnetic resonance imaging (MRI) findings in patients with
      suspected Parsonage Turner syndrome and to emphasize the value of an additional
      whole body MR scan to improve specificity of this diagnosis. MATERIAL AND
      METHODS: Three patients with proven Parsonage Turner syndrome referred for
      conventional MRI of the shoulder girdle and additional whole body turboSTIR MRI
      were included for study. RESULTS: In each case, imaging revealed edema in the
      muscles of the shoulder girdle. Whole body turboSTIR MRI scan confirmed localized
      unilateral changes in each case improving specificity and confidence in the
      diagnosis of Parsonage Turner syndrome in each case. CONCLUSION: Whole body
      turboSTIR MR imaging is a useful diagnostic tool in the evaluation of patients
      with suspected Parsonage Turner syndrome. Inclusion of the brain, neck, brachial
      plexus, and extremity musculature at whole body imaging allows differentiation
      from polymyositis and elimination of additional causes of shoulder girdle pain
      and weakness including gross lesions in the brain, neck, and brachial plexus by a
      single non-invasive study.

PMID- 15515517
TI  - Validation of diagnostic imaging based on repeat examinations. An image
      interpretation model.
AB  - PURPOSE: To develop an interpretation model, based on repeatedly acquired images,
      aimed at improving assessments of technical efficacy and diagnostic accuracy in
      the detection of small lesions. MATERIAL AND METHODS: A theoretical model is
      proposed. The studied population consists of subjects that develop focal lesions
      which increase in size in organs of interest during the study period. The imaging
      modality produces images that can be re-interpreted with high precision, e.g.
      conventional radiography, computed tomography, and magnetic resonance imaging. At
      least four repeat examinations are carried out. RESULTS: The interpretation is
      performed in four or five steps: 1. Independent readers interpret the
      examinations chronologically without access to previous or subsequent films. 2.
      Lesions found on images at the last examination are included in the analysis,
      with interpretation in consensus. 3. By concurrent back-reading in consensus, the
      lesions are identified on previous images until they are so small that even in
      retrospect they are undetectable. The earliest examination at which included
      lesions appear is recorded, and the lesions are verified by their growth (imaging
      reference standard). Lesion size and other characteristics may be recorded. 4.
      Records made at step 1 are corrected to those of steps 2 and 3. False positives
      are recorded. 5. (Optional) Lesion type is confirmed by another diagnostic test.
      CONCLUSION: Applied on subjects with progressive disease, the proposed image
      interpretation model may improve assessments of technical efficacy and diagnostic
      accuracy in the detection of small focal lesions. The model may provide an
      accurate imaging reference standard as well as repeated detection rates and false
      positive rates for tested imaging modalities. However, potential review bias
      necessitates a strict protocol.

PMID- 15515518
TI  - Detection of small implanted tumors growing during repeated magnetic resonance
      imaging of the rabbit liver: application of an interpretation model.
AB  - PURPOSE: To apply experimentally and further develop a new image interpretation
      model based on repeated imaging and aimed at improving assessments of technical
      efficacy and diagnostic accuracy in the detection of small lesions. MATERIAL AND
      METHODS: VX2 carcinoma was implanted in the liver of 14 rabbits as two 1.1-1.7
      mm3 cores. Magnetic resonance imaging was performed before and 4 days after
      implantation and then every second day up to the 14th to 20th day. One T2
      weighted sequence (TSE T2) and three T1-weighted sequences (SE T1, GE T1, and TFL
      T1) were used. Interpretation was performed stepwise: three readers independently
      interpreted image sequences chronologically (step 1). Tumors were included at the
      last examination (step 2). By concurrent interpretation of repeated examinations,
      the earliest day at which tumors became visible and tumor size were recorded
      (step 3). Records were corrected (step 4) and autopsy was performed (step 5). Two
      procedures for use in calculating repeated detection rates of tumors with
      different magnetic resonance imaging sequences are presented and discussed.
      RESULTS: Of 40 macroscopic tumors, 34 were included. They were mainly small (size
      range SE T1: 1-3mm, TSE T2: 1.5-5 mm) when they became visible as determined at
      step 3, which was consistently earlier than observed at step 1. TSE T2, SE T1,
      and GE T1 did not differ significantly regarding earliest day of detection (step
      3), while TFL T1 revealed the tumors later. The initial repeated detection rates
      were higher with TSE T2 than with the other sequences. Frequency of false
      positives varied over time, indicating fluctuating criteria for reporting tumors.
      CONCLUSION: A theoretical image interpretation model previously described proved
      to be applicable for detection of experimental liver tumors. The model was
      improved by introducing calculations of repeated detection rates for initial
      image interpretation using an imaging reference standard.

PMID- 15515519
TI  - Congenital infiltrating lipomatosis of the face and neck.
AB  - Congenital infiltrating lipomatosis is a rare clinicopathologic entity
      characterized by infiltrating lipomatous tumors which, although of benign nature,
      have a tendency to recur after surgery. This has a predilection for the
      extremities and the trunk and is seen as overgrowth of soft tissue and bone. It
      rarely affects the face and neck. We describe two cases of congenital
      infiltrating lipomatosis of face and neck depicting the bone and soft tissue
      changes seen on computed tomography, along with a review of the literature on the
      subject.

PMID- 15515520
TI  - Diffusion magnetic resonance imaging patterns in metabolic and toxic brain
      disorders.
AB  - PURPOSE: To evaluate metabolic and toxic brain disorders that manifest with
      restricted, elevated, or both restricted and elevated diffusion patterns on
      diffusion magnetic resonance imaging (MRI). MATERIAL AND METHODS: Echo-planar
      diffusion MRI examinations were obtained in 34 pediatric patients with metabolic
      and toxic brain disorders proved by appropriate laboratory studies. The MRI unit
      operated at 1.5 T with a gradient strength of 30 mT/ meter, and a rise time of
      600 micros. b=1000s/mm2 images and apparent diffusion coefficient (ADC) maps with
      ADC values were studied. RESULTS: Three patterns were observed: 1. A restricted
      diffusion pattern (high signal on b = 1000 s/mm2 images and low ADC values); 2.
      an elevated diffusion pattern (normal signal on b = 1000s/mm2 images and high ADC
      values); and 3. a mixed pattern (coexistent restricted and increased diffusion
      patterns in the same patient). Disorders manifesting with a restricted diffusion
      pattern included metachromatic leukodystrophy (n = 2), phenylketonuria (n = 3),
      maple syrup urine disease (intermediate form) (n = 1), infantile neuroaxonal
      dystrophy (n = 1), Leigh (n = 2), Wilson (n = 3), and Canavan disease (n = 1).
      Disorders with an elevated diffusion pattern included phenylketonuria (n = 1),
      adrenoleukodystrophy (n = 1), merosin-deficient congenital muscular dystrophy (n
      = 2), mucopolysaccharidosis (n = 2), Lowe syndrome (n = 1), Leigh (n = 2),
      Alexander (n = 1), Pelizaeus-Merzbacher (n = 1), and Wilson (n = 3) disease.
      Disorders with a mixed pattern included L-2 hydroxyglutaric aciduria (n = 2), non
      ketotic hyperglycinemia (n = 1), infantile neuroaxonal dystrophy (n =2), maple
      syrup urine disease (n = 1), and Leigh (n = 1) disease. CONCLUSION: The findings
      suggested that the three different diffusion patterns reflect the
      histopathological changes associated with the disorders and different stages of a
      particular disorder. It is likely that the restricted diffusion pattern
      corresponds to abnormalities related to myelin, and the elevated diffusion
      pattern to disintegration of the tissue. The mixed pattern has contributions from
      both myelin abnormalities related to myelin disintegration of the tissue.

PMID- 15515521
TI  - Multi-slice computed tomography angiography in the detection of residual or
      recurrent cerebral aneurysms after surgical clipping.
AB  - PURPOSE: To assess the diagnostic accuracy of multi-slice computed tomography
      (MSCT) angiography compared to digital subtraction angiography (DSA) in detecting
      residual or recurrent aneurysms in patients undergoing aneurysm clipping surgery.
      MATERIAL AND METHODS: Eight patients with nine aneurysms who had both MSCTA and
      DSA were included in the study. Two independent experienced neuroradiologists
      evaluated the examinations. RESULTS: Accuracy, sensitivity, and specificity of
      detecting residual or recurrent aneurysms on MSCTA were 0.80, 0.60, and 1.00,
      respectively. Positive and negative predictive values were 1.00 and 0.71,
      respectively. CONCLUSION: MSCTA is a promising technique for evaluating residual
      or recurrent aneurysms in patients undergoing surgical treatment of aneurysm with
      titanium clips.

PMID- 15515523
TI  - Partial unilateral intracavernosal hematoma in a long-distance mountain biker: a
      case report.
AB  - We present a case of spontaneous partial unilateral hematoma of the bulb of the
      corpus cavernosum in a long-mileage mountain biker. Ultrasonography, magnetic
      resonance imaging, and histopathological findings are described.

PMID- 15515522
TI  - Intracranial metastasis via transplacental (vertical) transmission of maternal
      small cell lung cancer to fetus: CT and MRI findings.
AB  - We present the computed tomography (CT) and magnetic resonance imaging (MRI)
      findings of brain metastases in an unusual case of a premature, 33-week
      gestational age neonate who was emergently delivered from a mother suspected of
      having lung cancer according to imaging performed during the third trimester of
      pregnancy. Owing to the presence of placental metastases noted after delivery,
      the fetus had initial screening with brain MRI and chest/abdomen CT as well as
      serial screening imaging studies during the first 5 months of life, all of which
      were apparently normal. However, serial examinations eventually revealed a
      cerebellar lesion that significantly improved after chemotherapy but recurred and
      enlarged within a few months. This lesion was later confirmed to be metastasis by
      subsequent biopsy and resection. More metastatic lesions were identified in the
      frontal and temporal lobes on follow-up MRI. In the setting of aggressive
      maternal malignancy (without known fetal primary malignancy) an intracranial mass
      can, on the exceedingly rare occasion, result from maternal high-grade malignancy
      and the neuroradiologist should be alerted to this phenomenon.

PMID- 15515524
TI  - Dynamic first pass 3D EPI of the prostate: accuracy in tumor location.
AB  - PURPOSE: To evaluate the potential of dynamic contrast enhanced (DCE) 3D EPI in
      the location of prostate cancer. MATERIAL AND METHODS: A DCE 3D EPI scan was
      included in the magnetic resonance imaging protocol for prostate examination.
      Twenty-eight patients who subsequently underwent radical prostatectomy were
      included in the study. T2-weighted (T2W) Turbo Spin Echo (TSE) images were
      initially evaluated by two radiologists. Parametric images reflecting contrast
      enhancement were added and new evaluations performed. The results were compared
      with histology from resected specimens. Accuracies and interobserver agreements
      were calculated. RESULTS: Interobserver agreement was Kw =49+/-3% for the T2W
      technique and Kw=30+/-3% for the combined techniques. No statistically
      significant advantages were found for location of tumor in the prostate or in the
      seminal vesicles by adding the DCE information. CONCLUSION: DCE 3D EPI did not
      improve tumor location compared with that of T2W TSE images. Further
      investigation is needed on how best to exploit the DCE technique.

PMID- 15515525
TI  - Combined MR examination of prostate: is it reliable?
AB  - A combination of magnetic resonance (MR) methods (T2-weighted MRI, proton MR
      spectroscopy, and dynamic contrast enhancement) gives the highest sensitivity and
      specificity for identification of prostate cancer by MRI. The prostate MR
      findings of a patient with a congenital cystic disease of seminal vesicle are
      presented. To our knowledge, this is the only case described in the literature.
      The MR examination resulted in a false-positive indication of prostate cancer.

PMID- 15515526
TI  - Chemotherapy is an important prognostic factor for thrombosis and stenosis
      arising from central venous catheterization.

PMID- 15515527
TI  - [The expression difference of VEGF, PDGF/dThdPase and MVD on primary
      hypopharyngeal carcinoma and metastasis lymph nodes].
AB  - OBJECTIVE: To evaluate the difference of angiogenic factors PDGF/dThdPase,VEGF
      expression and microvessel density (MVD) in primary hypopharyngeal tumor and
      metastasis lymph nodes. METHOD: The author studied immunohistochemically a series
      of 48 primary hypopharyngeal carcinoma patients and metastasis lymph nodes were
      calculated. RESULT: The percentage of VEGF was 25.38% in primary tumor and 21.52%
      in lymph nodes. No significant difference was found. The percentage of
      PDGF/dThdPase was 29.59% in primary tumor and and 21.2% in lymph nodes. This
      showed significent difference. VEGF showed significent difference between live
      and death group(P < 0.05) and among differentiation group (P < 0.05). MVD showed
      significant difference between live and death group, early and late stage group,
      and T1-2 and T3-4 group (P < 0.05). There were statistically significant
      correlations between the score of PDGF/ dThdPase, or VEGF and the score of MVD
      respectively. CONCLUSION: The present study suggests that there was a correlation
      between VEGF or PDGF and MVD. VEGF and MVD were possible to be prognostic
      discriminators in hypopharyngeal carcinoma. PDGF expression in lymph nodes was
      significant higher than in primary tumors, and MVD expression in primary tumor
      was significant higher than in lymph nodes.

PMID- 15515528
TI  - [The long term results of partial laryngectomy].
AB  - OBJECTIVE: To evaluate the long-term results of various kinds of partial
      laryngectomy. METHOD: The following-up materials from 264 patients who had
      undergone partial laryngectomy in this department from 3,1984 to 3,1998 wert
      analyzed. The pathological diagnosis of all the cases was squamous cell
      carcinoma. The surgical technique were divided into eight kinds: 1. laser vocal
      cord ectomy for 19 cases, 2. vocal cordectomy through laryngofissure for 29, 3.
      laterovertical partial laryngectomy for 58, 4. frontovertical partial
      laryngectomy for 18, 5. suproglottic partial laryngectomy for 42, 6.vertical
      horizontal partial laryngectomy for 29, 7. extended subtotal laryngectomy for
      51(extended to the base of tongue 23, to pyriform recess 25, to trachea 3), 8.
      subtotal laryngectomy for 18 (including 3 cases of middle segment partial
      laryngectomy and hypopharynx-trachea anastomasis). One hundred thirteen cases
      (146 sides) received neck dissection simuteniously. The materials that were used
      to reconstruct the operative defect simply or in combination included cervical
      myocuteneous flap, cervical myofascia flap, false cord, local laryngeal mucosa,
      thyroid perchondrium and epiglottis. RESULT: All the patients restored the
      function of phonation. No aspiration happened in 89 cases,mild aspiration in
      112,moderate in 57 and severe in 6 cases. But the aspiration disappeared after a
      certain time of practice and the swallowing function restored in all patients.
      The rate of decannulation was 82.95%. The survival rate of 3-year,5-year and 10
      year was 86.74% ,78.47% and 53.33%, respectively. The main causes of death were
      local recurrence and lymphatic metastasis, and 71.4 percent of the death happened
      in the first 3 years. CONCLUSION: The partial laryngectomy was a racial surgery
      as the same as total laryngectomy. The key point to success was to apply the
      operative indication strictly. And the important landmark of the patients'
      survival quality was the decannulation rate and the restoration of laryngeal
      functions. Correct management on cervical lymphatic nodes could raise the 3-year
      and 5-year survival rate.

PMID- 15515529
TI  - [Expression of transforming growth factor-betal (TGF-beta1) and its role in human
      laryngeal and hypopharyngeal carcinoma].
AB  - OBJECTIVE: To detect the mRNA expression of transforming growth factor-betal (TGF
      beta1) in laryngeal and hypopharyngeal carcinoma, and to explore the pathogenesis
      of the two types neoplasms. METHOD: We examined the expression of TGF-beta1 mRNA
      in the tissue of human laryngeal and hypopharyngeal carcinoma from patients. The
      TGF-beta1 mRNA expression was determined by semi-quantitative reverse
      transcription polymerase chain reaction (RT-PCR). RESULT: The TGF-beta1 mRNA
      expression was significantly stronger in 17 cases of 20 laryngeal and
      hypopharyngeal carcinoma. CONCLUSION: The result suggested that the expression
      level of TGF-beta1 in laryngeal and hypopharyngeal carcinoma may inhibit the
      human immunity and enhance the growth and metastasis of the laryngeal and
      hypopharyngeal carcinoma.

PMID- 15515530
TI  - [Correlation of the expression of MDR genes and MDR genes-coded product with
      prognosis in laryngopharyngeal malignant melanoma].
AB  - OBJECTIVE: To study the correlation of expression implication of MDR genes (GST
      pi and Topo II) and MDR gene-coded product (Pgp) with prognosis in
      laryngopharyngeal malignant melanoma. METHOD: Using immunohistochemical S-P
      method,expression of GST-pi, Topo II and Pgp was detected in 28 cases of
      laryngopharyngeal malignant melanoma. The relationship between GST-pi, Topo II,
      Pgp and clinicopathological features, prognosis of the tumors were also analyzed.
      RESULT: The positive rates of Pgp, GST-pi and Topo II were 35.7%, 57.1% and 46.4%
      respectively in 28 cases of laryngopharyngeal malignant melanoma, without
      significant difference (P > 0.05). The positive rates of Pgp, GST-pi and Topo II
      were not correlated with sex,age, size of tumor and Clark's grade, Breslow's
      grade (P > 0.05), but AJC grade and prognosis (P < 0.05). CONCLUSION: Expression
      of Pgp,GST-pi and Topo II may be the chief mechanism of multi-drug resistance.
      Detection of multi-drug resistance genes is of necessity and feasibility when
      predicting the effect of chemotherapy.

PMID- 15515531
TI  - [Long-term results of one stage tracheoesophageal end-side anastomosis voice
      restoration after total laryngectomy].
AB  - OBJECTIVE: The purpose of this study is to discuss long-term results of one
      different kind of voice restoration after total laryngectomy with 10 years
      experience. METHOD: One stage tracheoesophageal end-side anastomosis after total
      laryngectomy was performed in 36 patients from 1991-1996. The key technique of
      this operation is to make a tongue-ship flap(1.5 cm x 1.5 cm-1.8 cm x 1.5 cm)
      with tracheal membranous part and dissect it from the esophagus to 1 cm below the
      upper incisal margin of trachea. Then a 0.8 cm middle vertical incision was made
      on the lowest anterior wall of the separated esophagus. Folding the tongue-ship
      flap posteriorly to approximate the esophagus incision and make an end-side
      anastomosis. Close the upper incisal margin of trachea with left to right
      direction suture. The follow up time is 5 - 10 year. One lost follow 2.5 years
      later and was judged as dead. RESULT: The short-term and long-term success rate
      were 69% (25/36) and 83% (30/36) respectively. The 3-, 5- and 10 year survival
      rate are 72%, 69%, 69%, respectively. CONCLUSION: This technique does not change
      the pattern of total laryngectomy and various neck dissections do not affect
      voice rehabilitation. Advantages of the operation: easy to operate and learn; the
      special form of tracheoesophageal shunt (high in the tracheal side and low in
      esophageal side) prevents the aspiration; high successful rate, excellent speech,
      fluent language, good acceptability and lower aspiration.

PMID- 15515532
TI  - [The comparison of treatment modalities for obstructive sleep apnea syndrome].
AB  - OBJECTIVE: To analyse the curative effects of various treatment modalities for
      obstructive sleep apnea syndrome. METHOD: 52 cases of patients were divided into
      two groups according to the methods of treatment. In group 1, 29 cases only
      received uvuloplatopharygoplasty (UPPP). In group 2, 23 cases received
      multimodality treatments by various combinations of UPPP, continuous positive
      airway pressure (CPAP) and the device of prosthetic dentitry. RESULT: The
      comparison between the short-term effects of two groups did not reveal
      statistically significant difference, but complications easily occurred in
      patients who did not receive CPAP before UPPP. The long-term effects of two
      groups were also compared, the difference was statistically significant.
      CONCLUSION: Multimodality treatment is an effective approach to improve the long
      term effects of patients with OSAS.

PMID- 15515533
TI  - [A comparison of the closed reduction of arytenoid dislocation under indirect and
      direct laryngoscope].
AB  - OBJECTIVE: To assess the curative effects of the dislocation of cricoarytenoid
      joint caused by intubation, indirect laryngoscope (IL) and direct laryngoscope
      (DL) were utilized to the closed reduction of the displaced arytenoid under local
      anesthesia. METHOD: 23 patients who underwent the reduction for dislocated
      arytenoid by IL or DL from Jan 1991 to Jun 2001 have been reviewed, the records
      were made as follows: The duration of the laryngeal injury; The number of times
      for the reduction; The side-effective following the treatment; The period of
      complete return of normal voice. The relation between the duration of the
      laryngeal lesion and the period of the voice rehabilitation has been studied.
      RESULT: 13 patients and 10 patients were respectively arranged to perform the
      reduction by IL and DL. Except that a comparison on the times of the reduction is
      significantly different, the difference between IL group and DL group in the
      course and the period of voice rehabilitation, as well as sore throat after the
      manipulation are not significant. The patients' voice recovery is positively
      relative to their course, regardless of IL or DL, group. CONCLUSION: The recovery
      of normal voice is obviously affected by the duration of arytenoid dislocation.
      The reduction by IL is as successful as by DL in the treatment of arytenoid
      dislocation. It is very suitable for the patient having his injury for a longer
      time to receive the reduction by DL.

PMID- 15515534
TI  - [Unilateral tonsillar enlargement and malignant tonsillar lymphoma].
AB  - OBJECTIVE: To study clinic characters of malignant lymphoma in patients with
      unilateral tonsillar enlargement for early discover and synthetic therapy clinic
      characters of malignant lymphoma patients with unilateral tonsillar enlargement
      for early discover and synthetic therapy. METHOD: 10 cases of non-Hodgkin's
      lymphoma (NHL) out of 100 unilateral tonsillar enlargement patients given
      tonsillectomy were treated with combined chemotherapy. 8 cases of 10 underwent
      local radiotherapy after operation. RESULT: 5 years survival rate was 60% in 10
      patients with NHL. CONCLUSION: Progressing unilateral swollen tonsil found in a
      short time with suspicious appearance should be given tonsillectomy for
      histopathology; upper airway and systematic symptoms such as fever and rigors,
      night sweats; lymphatic enlargement in cervical, axillary, inguinal region;
      hepatosplenomegaly should be thought of main traits of malignant lymphoma, and
      hyposensitivity to medicine should be taken malignant lymphoma into account.

PMID- 15515535
TI  - [The distribution of metastatic cervical lymph nodes in laryngeal carcinoma].
AB  - OBJECTIVE: To detect regularity of lymph nodes metastasis of laryngeal carcinomas
      and determine the best kind of neck dissection. METHOD: The series consist of
      three parts:the distribution of laryngeal carcinoma with metastasis lymph nodes,
      the immunohistochemical evaluation of micrometastases after pathologic diagnostic
      N0, the distribution of recurrence after operation. All 289 cases in these series
      including 174 cases of supraglottic carcinoma, 113 cases of glottic carcinomas
      and 2 cases subglottic carcinomas. RESULT: In the first part, there were 242
      necks had been conducted neck dissections and the metastases rates from level I
      to level VI is 2.8%, 98.3%, 32.6%, 15%, 13%, 21.4% respectively. In the second
      part, 46 (50 necks) of 71 cases of pathologic N0 necks conducted
      immunohistochemical study in the lymph nodes. 13 lymph nodes harbor
      micrometastases, which distributes in 11 cases. All the positive lymph nodes
      located in level II. In the third part, 45 necks of 37 cases were evaluated the
      cervical metastasis without neck dissection. The metastases rates from level I to
      level V is 2.2%, 100%, 48.9%, 26.7%, 13.3% respectively. CONCLUSION: The
      metastatic lymph nodes of laryngeal carcinomas distribute mainly in level II and
      level III, followed by level IV and level VI, but rarely in submandibular and
      posterior triangles. The neck dissection of laryngeal carcinomas should be
      conducted in the regions from level II to level IV. The dissection of level I and
      level V should be spared unless there is evidence of metastasis to these regions
      so as to shorten the operation time and avoid postoperative complications.

PMID- 15515536
TI  - [The study of vascular endothelial growth factor in nasopharyngeal carcinoma
      patients before and after radiotherapy].
AB  - OBJECTIVE: The purpose of this study was to determine the serum vascular
      endothelial growth factor (VEGF) level before and after radiotherapy in the
      nasopharyngeal carcinoma. METHOD: In this study we used the methods of ELISA to
      test the serum VEGF level of 66 cases which including 46 cases of nasopharyngeal
      carcinoma and 20 cases of healthy controls. RESULT: The serum VEGF levels in
      nasopharyngeal carcinoma patients were significantly higher than those of healthy
      controls (P < 0.01). The serum levels of VEGF were significantly reduced at the
      end of radiotherapy (P < 0.01). The recurrence or metastasis rate was
      significantly higher in cases with > 150 ng/L VEGF level than those with < 150
      ng/L. CONCLUSION: VEGF plays an important role in the growth and prognosis of
      nasopharyngeal carcinoma.

PMID- 15515537
TI  - [The curative effect observation of shuanghuanglian and penicillin on acute
      tonsillitis].
AB  - OBJECTIVE: To investigate the curative effect of shuanghuanglian on acute
      tonsillitis. METHOD: 95 cases of acute tonsillitis were randomly divided into
      shuanghuanglian group (treatment group) and penicillin group (control group).
      RESULT: The total effective rate in treatment group was 87.5%, hardly less than
      that (83.0%) in control group (P > 0.05). CONCLUSION: Shuanghuanglian was an
      effective medicine in the treatment of acute tonsillitis, in addition, it was
      effective for virus infection.

PMID- 15515538
TI  - [An experimental study on repair of laryngeal cartilage defect with the bone
      morphogenetic protein composite].
AB  - OBJECTIVE: To study the effects of the bone matrix gelatin and composite of bone
      morphogenetic protein and fibrin glue (BMP-FG) on the repair of thyroid cartilage
      defect. METHOD: Full-thickness defects measuring 0.4 cm x 0.4 cm were created in
      four sections in thyroid cartilages of 20 adult dogs. The defects were divided
      into 4 groups by the sections they in. Group A was empty group, without implant;
      Group B were repaired by implanted with hydroxylapatite; Group C with bone matrix
      gelatin (containing BMP); Group D with bone morphogenetic protein-fibrin glue
      composite. The animals were killed separately at 2, 4, 12 weeks after operation.
      The effects of repair were analyzed by routine histological examination and
      electron microscope. RESULT: In the BMP-FG implanted group, the result showed
      complete absorption of the implant and substitution by new-formed cartilage and
      bone. The defects in the BMG group regenerated less cartilage and bone, the
      inflammation was sever. The gross appearance and histological features of HA
      group were similar to the empty group. CONCLUSION: Both BMP-FG and BMG can induce
      cartilage and bone regeneration to repair the defect of thyroid cartilage. BMP-FG
      has a better effect.

PMID- 15515539
TI  - [Experimental study of taxol combining accelerated radiation on laryngeal
      carcinoma cells].
AB  - OBJECTIVE: To investigate the effect of taxol combining accelerated radiation on
      the human laryngeal squamous cell carcinoma Hep-2 cell lines in vitro, and to
      provide the experimental basis for the usage of these two combined theraputic
      methods. METHOD: Using techniques of tumor cells culture in vitro, the
      suppressive and time-dependency effects of taxol (1 x 10(-8) mol/L) combine 2 Gy
      X-rays generated by accelerator on the human laryngeal squamous cell carcinoma
      Hep-2 cell lines were observed. RESULT: Cell growth is obviously suppressed in
      group taxol combined accelerated radiation and it's livability is 11.11%, much
      lower than accelerated radiation combined taxol. After adding taxol 12 h or 24 h
      then combined accelerated radiation, the two groups were no difference
      statistically. Cell livability of group taxol is lower than group accelerated
      radiation. CONCLUSION: Cell growth is obviously suppressed in the human laryngeal
      squamous cell carcinoma Hep-2 cell lines after given 1 x 10(-8) mol/L taxol
      combined 2 Gy X-rays generated by accelerator. Taxol acts as a radiation
      sensitizer.

PMID- 15515540
TI  - [Microcirculation evaluation of the maxillary sinus mucosa in patients with
      chronic sinusitis].
AB  - OBJECTIVE: To evaluate the microcirculation change in the maxillary sinus mucosa
      of patients with chronic sinusitis. METHOD: The microcirculation blood flow in
      the maxillary sinus mucosa of 20 patients with chronic sinusitis and 10 healthy
      controls was evaluated by means of nasal endoscopy-guided laser Doppler
      flowmetry. RESULT: The microcirculation blood flow were significantly reduced in
      the maxillary sinus mucosa of patients with chronic sinusitis (including type I
      and type II) compared with healthy controls(P<0.05, P<0.01). There were no
      significantly difference between the two types of chronic sinusitis. CONCLUSION:
      The microcirculation blood flow were reduced in the maxillary sinus mucosa of
      patients with chronic sinusitis.

PMID- 15515541
TI  - [Noninvasive and invasive naso-sinus fungus: 35 cases report].
AB  - OBJECTIVE: To study the clinical features, diagnosis and management of nose and
      nasal sinuses fungus. METHOD: Different manner of surgical procedure was taken
      according to the areas and degree of pathological changes. The patients with
      noninvasive fungus were treated with radical maxillary sinusotomy (cald-well-Luc
      operation) or endoscopic sinus surgery. The patients with invasive form were
      undergone by the sinusotomy of enlarging areas, and combined with a
      postoperatively antifungal therapy. RESULT: Twenty-six patients were involved in
      noninvasive fungus, and 25 cases in them were cured in single surgery through
      different manner. Nine patients were in invasive one, and 7 in them were also
      cured by single surgery in different manner. One patient with invasive fungus
      died 5 months postoperatively for extensive area and non effective treatment
      although four surgical excisions were done. CONCLUSION: CT scan is very important
      in their diagnosis, and the histopathology leads to identification of the fungus.
      Surgical removal is a radical kind of treatment. It is essential to excise and
      open entirely the involved sinus cavity whatever type,and to enlarge areas for
      the extensive invasive fungus.

PMID- 15515542
TI  - [Transnasal endoscopic sinus surgery for diseases in the ethmoid-sphenoid area].
AB  - OBJECTIVE: To explore the proprieties of diseases in the ethmoid-sphenoid area
      and improve the effects of treatment and diagnose of these kinds of diseases.
      METHOD: 51 cases of diseases in the ethmoid-sphenoid areas,who had undergone
      transnasal endoscopic sinus surgery, were investigated. Among them, 41 cases of
      diseases in the ethmoid-sphenoid area involved at the same time were undergone
      surgery by ethmoid approach, 10 cases with isolated sphenoid diseases were done
      via nasal cavity. RESULT: Forty-eight cases did not develop serious complications
      after surgical treatments, and 3 cases recurrence during the follow-up.
      CONCLUSION: Diseases in the ethmoid-sphenoid area readily ignored because there
      are few specific early-stage symptoms. Computer-tomographer scan is helpful to
      the diagnose and introductive to the procedure of surgery. Transnasal endoscopic
      sinus surgery can make patients suffer less, and leaves no scar in the face.

PMID- 15515543
TI  - [Study of computed tomographic dacryocystography used in endoscopic intranasal
      dacryocystorhinostomy preoperatively].
AB  - OBJECTIVE: To study computed tomographic dacryocystography used in endoscopic
      intranasal dacryocystorhinostomy preoperatively. METHOD: Ten volunteers and
      twelve patients with dacryocystitis were undergone the coronary and axial
      computed tomographic dacryocystography. RESULT: According to the anatomic
      relationship between anterior ethmoid sinus and fossa of lacrimal sac, the cells
      of anterior ethmoid sinus were classified into three typies: the result was that
      type I accounted for 12 sides (27.3%), type II 18 sides (40.9%), type III 14
      sides (31.8%) by analysing the data of axial dacryocystographies; the sites of
      obstruction were connection of the lacrimal sac with nasolacrimal duct, the form
      of lacrimal sac of 11 patients was normal or enlarged lacrimal sacs, bilateral
      cricatrized lacrimal sacs were found in one patient by analysing the data of
      coronary dacryocystographies. CONCLUSION: Computed tomographic dacryocystography
      preoperatively can provide significant clinical guidance for the endoscopic
      transnasal dacryocystorhinostomy in locating the site of bone-opening.

PMID- 15515544
TI  - [Implantation of complex tissue flap for atrophic rhinitis].
AB  - OBJECTIVE: To improve the treatment effect of atrophic rhinitis. METHOD: Twenty
      one cases (thirty-one sides) of atrophic rhinitis were treated by implantation of
      complex tissue flap to narrow the nasal cavity. RESULT: Short-term effective
      treatment results were 100% (21/21), long-term effective treatment results were
      90.5% (19/21). CONCLUSION: Implantation of complex tissue flap offers a simple
      and effective way and can be recommended for the treatment of atrophic rhinitis.

PMID- 15515545
TI  - [Expression of p15 protein in poorly differentiated nasopharyngeal carcinoma].
AB  - OBJECTIVE: To explore the role of p15 protein in the pathogenesis of poorly
      differentiated nasopharyngeal carcinoma (NPC). METHOD: Using immunohistochemical
      LSAB (Labeled Streptavidin Biotin method), we examined 55 samples of poorly
      differentiated NPC and 15 samples of nasopharyngeal normal tissue for expression
      of p15 protein. RESULT: The p15 protein expression was located in the cytoplasm
      and nuclear membranes. The positive rate of p15 protein in NPC is significantly
      lower than that in normal tissue (P < 0.05). Important correlations were found
      between the p15 protein expression and clinic stages, T classification of NPC.
      But p15 protein wasn't correlated to neck lymph node metastasis and 5-years
      survival rate. CONCLUSION: The absence of p15 protein may play an important role
      in the pathogenesis and development of NPC, the expression of p15 protein may be
      used to evaluate the biological behavior of NPC.

PMID- 15515546
TI  - [Semiconductor laser use in endoscopic transnasal dacryocystorhinostomy].
AB  - OBJECTIVE: To explore the using and value of semiconductor laser in endoscopic
      transnasal dacryocystorhinostomy. METHOD: In 8 cases with obstruction of
      nasolacrimal duct, after being had submucous resection of nasal septum, nasal
      polypectomy or sinus resection, we used the fiberoptic light probe through the
      canalis nasolacrimalis to confirmed the location of sacculus lacrimalis and
      resected the mucosa and bone on lateral wall of nasal cavity that covering the
      sacculus lacrimalis. RESULT: Six months after operation, the mucous was complete
      epithelization and ostium without stricture in seven cases. One case was covered
      with ulo, after reexcised with semiconductor laser and put the silicon through
      the canalis nasolacrimalis, the ostium without stricture in 6 months. CONCLUSION:
      Semiconductor laser can obviously reduce bleeding,adhesion and granulation
      tissue,it is a good, simply and shortcut way for clinic.

PMID- 15515547
TI  - [Expression and significance of serum sICAM-1 and sCD4 & sCD8 in patients with
      nasopharyngeal carcinoma].
AB  - OBJECTIVE: To study the expression of serum sICAM-1 and sCD4 & sCD8 antigens in
      patients with nasopharyngeal carcinoma and clinical significances. METHOD: The
      serum levels of sICAM-1 and sCD4 & sCD8 antigens were determined in 54 patients
      with nasopharyngeal carcinoma (NPC group) and 32 healthy adults (normal group) by
      ELISA. RESULT: Expressions of serum sICAM-1 and sCD4 & sCD8 antigens in NPC group
      were significantly higher than that in normal group (P < 0.01, respectively). The
      levels of serum sICAM-1 in patients with III-IV stages were higher than those
      with I-II stages (P < 0.05), and those in patients with no lymph node metastasis
      lower than in lymph node metastasis (P < 0.01); but the serum levels of sCD4 and
      sCD8 antigens were not related to UICC-TNM stages in nasopharyngeal carcinoma (P
      > 0.05). The levels of serum sICAM-1 and sCD4 & sCD8 antigens decreased
      significantly in disappearance of tumor and metastatic lymph node after
      radiotherapy (P < 0.01). CONCLUSION: sICAM-1 might be involved in the cellular
      immunopathogenesis of nasopharyngeal carcinoma, and the measurement of the serum
      sICAM-1 and sCD4 and sCD8 antigens may reflect ability of neoplasm cell in
      freedom from host immunological surveillance. Dynamic measurement of serum sICAM
      1 and sCD4 and sCD8 antigens may be a useful objective index to evaluate
      prognosis and curative effects of nasopharyngeal carcinoma.

PMID- 15515548
TI  - [Prognostic value of the urokinase-type plasminogen activator and its inhibitors
      in squamous cell carcinoma of human larynx].
AB  - OBJECTIVE: The aim of the present study was to evaluate whether the expression of
      uPA parameters might be of clinical value in squamous cell carcinoma of human
      larynx as a tumor/biologically defined risk factor. METHOD: In a consecutive
      series of 127 patients resected for primary squamous cell carcinoma of human
      larynx, the expression of uPA and plasminogen activator inhibitors (PAI) type-1,
      type-2 was determined immunohistochemically. The results were classified as
      positive and negative. Patients were followed-up prospectively for a median of 41
      months(rang 6 to 84 months). Overall survival were analyzed according to Kaplan
      Meier and log-rank statistics, the prognostic relevance of uPA, PAI-1, PAI-2 and
      conventional prognostic factors were analyzed by Cox analyses. RESULT: These
      revealed a high significant inverse correlation of uPA positive expression
      survival time(P = 0.006); and patients with PAI-2 positive expression had a
      significantly longer survival time than those with PAI-2 negative expression(P =
      0.009); in different clinicopathological parameters subgroups uPA, PAI-2 added
      significant survival information, whereas PAI-1 positive expression did not
      associate with prognoses. Patients with uPA-positive/PAI-2-negative expression
      had the poorest prognoses. Multivariate analysis revealed that four independent
      prognostic factors for overall survival time were uPA, PAI-2, lymph node
      metastasis and differentiation of tumor, P = 0.0002, 0.0001, 0.0117, 0.0436
      respectively, relative risk and 95% confidence interval were 1.99 (1.39 to 2.85)
      0.36 (0.212 to 0.609), 2.36 (1.21 to 4.61) 1.51 (1.01 to 2.25) respectively.
      CONCLUSION: We conclude that uPA and PAI-2 are new independent and strong
      biologically prognostic factors, uPA positive expression may be a powerful aid in
      evaluating metastatic potential and high risk patients in early stage of human
      larynx carcinoma.

PMID- 15515549
TI  - [The therapeutic effects of basic fibroblast growth factor injected into tympanic
      cavity on sensorineural deafness].
AB  - OBJECTIVE: To evaluate the therapeutic effects of basic fibroblast factor (bFGF)
      ototopically injected into tympanic cavity on sensorineural deafness. METHOD: 40
      cases (50 ears) suffering from sensorineural deafness have been treated with
      bFGF,which was injected into tympanic cavity from 1998 to 1999. The hearing
      threshold of post-therapy was compaired with that of pre-therapy. RESULT: The
      total therapeutic effective rate of bFGF on the deafness was 96%. The hearing
      threshold of post-therapy was much lower than that of pre-therapy in average.
      CONCLUSION: The bFGF could improve the hearing of sensorineural deafness
      patients. The method of ototopically injecting bFGF to tympanic cavity was safe
      and applicable.

PMID- 15515550
TI  - [The ECochG in patients with auditory neuropathy].
AB  - OBJECTIVE: The purpose of this study was to investigate the ECochG in subjects
      with auditory neuropathy (AN). METHOD: The ECochG was recorded from ear canal
      electrode in patients with auditory neuropathy and normal subjects. The
      difference of their -SP amplitudes was compared. RESULT: The -SP was present in
      all AN ears and its amplitudes were significantly larger than those in normal
      subjects (P < 0.01). A low amplitude wave AP was present in 84% AN ears.
      CONCLUSION: The -SP was present in all AN ears and its amplitudes were larger.

PMID- 15515551
TI  - [The study of the enzyme histochemistry changes of thyroarytenoid when one side
      of RLN was excised].
AB  - OBJECTIVE: To chronologically evaluate the changes in both sides of
      thyroarytenoid (TA) muscles. when one side of recurrent laryngeal nerve (RLN) was
      cut off. METHOD: In 7 adult mongrel dogs, 2 dogs for control and the other 5 dogs
      for the following experiment: a 2 cm segment of right RLN was excised under
      intraperitoneal sedation. The animals were killed at 2, 4, 6, 8, 10 week
      respectively and the thyroarytenoid were processed for histochemical reaction and
      electromicroscope. The mean muscle fiber, standard deviation and muscle fiber
      type composition were determined. RESULT: For the injured sides, denervation
      resulted in shrinking of all the fibers at four weeks. At ten weeks, however, all
      the muscles were fibrosed. For the uninjured sides (left side), TA diameter
      appeared compensatory changes at four weeks, this changes were obvious at ten
      weeks. Variability of the fiber composition was observed throughout the study;
      however, there was no specific trend in changes before ten weeks. CONCLUSION:
      When the RLN was excised, the fibers in the uninjured side of thyroarytenoid
      appeared compensatory changes in fiber diameter, which could give rise to the
      recovery of the laryngeal function.

PMID- 15515552
TI  - [Changes of axoplasmic transportation during experimental facial nerve
      regeneration].
AB  - OBJECTIVE: To determine the roles of axoplasmic transportation during
      regeneration after facial nerve injury. METHOD: Facial nucleus injection and
      isotopic-label tracer with liquid scintillation counting techniques were used to
      investigate the changes of radioactivity after guinea pig facial nerve
      compressed. RESULT: Axoplasmic transportation was observed again at 3 d after
      facial nerve injury, and the function recovered until 14 d. At 21 d after injury,
      it showed that transportation curve of radiolabeled protein was similar with that
      of the normal. There was particular curve in slow axoplasmic transportation that
      included two wave: W1 and W2. The axons regenerated at a rate of (2.84 +/- 0.12)
      mm/d in fast transportation while that of slow transportation is (3.16 +/- 0.08)
      mm/d. CONCLUSION: It suggests that axoplasmic transport act as a important role
      during the course of facial nerve regeneration.

PMID- 15515554
TI  - [Primary culture of strial marginal cells of guinea pig cochlea].
AB  - OBJECTIVE: For further study of the function of marginal cells, primary cultures
      of marginal cells of guinea pig were established. METHOD: Tissue of stria
      vascularis was transferred from the cochlea to a cell-cultured dish using the
      explants culture technique. Explants were cultivated at 37 degrees C in a 5% CO2
      incubator and examined daily by interted microscopy. The culture medium was
      changed twice a week. Antibodies of cytokeratin and vimentin were used to examine
      the cultured cells by immunohistochemical methods. The ultrastructure of the
      cultured cells was observed by making the electron microscopy specimens. RESULT:
      Explants were successfully cultivated for 4 weeks. Two different cells, hexagonal
      shaped cells and spindle-shaped cells were observed. Cytokeratin and vimentin
      staining occurred in cytoplasm of hexagonal-shaped cells, whereas spindle-shaped
      cells gave a negative cytokeratin staining but a positive vimentin staining.
      Electron microscopy of the explants revealed that hexagonal-shaped cells have the
      epithelial morphologic characteristics such as tight junctions and desmosomes.
      CONCLUSION: Primary culture of marginal cells by explants culture technique
      provides an optimal model for investigation of the function of the marginal
      cells.

PMID- 15515553
TI  - [An experimental study on the therapeutic effects of eustachian tube surfactant
      in barotitis media].
AB  - OBJECTIVE: To observe the effect of surfactant on eustachian tube (ET) on the
      opening of ET as well as it's therapeutic role in barotitis media (BM). METHOD:
      50 guinea pigs were successfully established as BM models by stimulated ascending
      in altitude chamber. Parts of the models were treated with by middle ear flushing
      with nature ETS, artificial ETS, artificial phospholipid and saline, after which
      the eustachian tube pressure opening level (POL) of each group was tested. Others
      were injected with 1 ml artificial ETS in on side of the middle ear, and 1 ml of
      saline in the other served as control. RESULT: Natural ETS decreased the POL from
      11.98 to 6.11 kPa (P < 0.01); Artificial ETS reduced the POL from 11.91 to 6.67
      kPa (P < 0.01), there were no significant differences between the two groups.
      Artificial phospholipid decreased the POL from 11.86 to 8.61 kPa (P < 0.05),
      which was not as effective as natural ETS. While the POL of saline group remained
      unchanged. After one week of artificial ETS treatment, the congestion in drum
      membrane alleviated, the hearing threshold of ETS group improved and the effusion
      in tympanic cavity lessened. CONCLUSION: The results suggest that artificial ETS
      is as effective as nature ETS to facilitates the opening of eustachian tube.
      Artificial ETS may exert therapeutic effects on BM.

PMID- 15515555
TI  - [Sudden deafness with large vestibular aqueduct (case report and literatures
      review)].
AB  - OBJECTIVE: To study the clinical feature of large vestibular aqueduct syndrome
      and diagnostic basis of large vestibular aqueduct on high resolution computer
      tomography. METHOD: Report a 18 year old man who presented a sudden deafness in
      right ear and his left ear arised the same disorder before 11 months. Since
      childhood his both ears have occurred sensorineural hearing loss, which
      causations were reserved unknown. The temporal bone axially oriented high
      resolution computer tomography scanning showed a enlarged vestibular aqueduct
      without associated cochlear anomalies of both ears. In addition the literatures
      about this disorder are reviewed. RESULT: The large vestibular aqueduct syndrome
      without association cochlear anomalies may occurs acquired sensorineural hearing
      loss and appears to be at high risk for sudden deafness. CONCLUSION: It is
      important to identify followed by high-resolution computer tomography whether a
      large vestibular aqueduct syndrome when a causal uncertain sensorineural hearing
      loss or/and a sudden deafness onset in childhood is represented.

PMID- 15515556
TI  - [Auditory neuropathy].
AB  - OBJECTIVE: To explore the clinical and auditory functional feature of auditory
      neuropathy(AN). METHOD: The clinic signs, audiometric test and electrophysiology
      were analyzed on 54 cases of AN. RESULT: 70 ears had low frequency pure tone
      hearing loss. 24 ears had cover basic hearing threshold. 6 ears had flat hearing
      threshold. 4 ears showed high frequency hearing loss. The average low-frequency,
      median-frequency and high-frequency hearing threshold were 67.63 +/- 15.30, 43.61
      +/- 16.28 and 32.25 +/- 14.80 dB HL respectively. The tympanograms are normal. 77
      ears lost acoustic reflex. 31 ears increased acoustic reflex threshold. All of
      them induced no ABR and had normal DPOAE with 26 cases' contralateral acoustic
      suppression uninfluenced. 16 cases had controversial pure tone threshold compared
      with speech discrimination. 23 had normal temporal bone CT image or MRI. 10 cases
      accompanied with peripheral neuropathy. CONCLUSION: Abnormal ABR, normal DPOAE,
      unparallel pure tone threshold to speech audiometry, loss of stapedial acoustic
      reflex and OAE contralateral acoustic suppression, loss of the pure tone
      threshold primarily in low-frequency SNHL are the important features of AN, which
      shows that the lesioned site may lie at the intracochlear acoustic nerve. It is
      necessary to differentiate it from the common SNHL and central nerve hearing
      loss.

PMID- 15515557
TI  - [Surgical treatment of inflammatory labyrinthine fistulae 23 cases].
AB  - OBJECTIVE: To report the experience of surgical treatment of inflammatory
      labyrinthine fistula (LF). METHOD: Twenty-three patients with cholesteatomatous
      otitis media complicated with LF underwent mastoidectomy, surgical repair and
      obliteration of LF. After removal of cholesteatoma matrix and inflammatory lesion
      around fistula, the fistulae were treated as following procedures: fistulae less
      than 2 mm in diameter were overlaid with fascia (7 cases), those 2 to 3 mm were
      obliterated with bone chips and fascia (13 cases), and for those more than 3 mm,
      the bony semicircular canal lumen were packed with fascia and bone chips, then
      overlaid with fascia. RESULT: In 23 patients with LF, which included 22 lateral
      semicircular canal fistulae (SCF) and one lateral combined with posterior SCF,
      two patients lost follow-up and 21 cases were observed with an average follow-up
      period of 2.5 years. In this series of cases, vertigo disappeared in 17 and
      diminished in 2. With the exception of total deafness in two cases, the average
      auditory thresholds in speech frequencies remained unchanged, showing that the
      thresholds of air conduction (AC) and bone conduction (BC) were 67.1 dB HL and
      37.1 dB HL prior operation versus 69.1 dB HL and 30.6 dB HL after operation,
      respectively. CONCLUSION: Because of structural barrier between superior and
      inferior labyrinth and inflammatory adhesions, surgical treatment of inflammatory
      LF is feasible and effective. Successful operation depends on excellent
      microsurgery skill, complete removal of inflammatory lesion, precise obliteration
      of fistula, post-operative administration of antibiotics and steroids and close
      follow-up. In addition to fistula test, axial petrous bone CT scan is a good
      complemental method in preoperative diagnosis of LF.

PMID- 15515558
TI  - [Characteristics of tympanic cavity pressure and static compliance in 0-6 years
      old children].
AB  - OBJECTIVE: To explore the characteristics of tympanic cavity pressure and static
      compliance in different years old children. METHOD: 302 cases (567 ears) were
      studied. All cases were divided into five groups according to their age. Their
      tympanic cavity pressure and static compliance were tested. RESULT: Most tympanic
      cavity pressure ranged from +50 to -50 dapa in all groups. The volume of static
      compliance in group one is the largest (0. 71 ml), and it changed with the age.
      It gradually decreased from 3 month to 3 years old but increased after three
      years old until 6 years old then returned to the level in 1 year old. CONCLUSION:
      The tympanic cavity pressure and static compliance are relevant to the age when
      children are small than 6 years. This characteristic must be considered on clinic
      diagnosis of middle ear disease and the evaluation of hearing.

PMID- 15515559
TI  - [Analysis on the restenosis of post canaloplasty of external auditory canal].
AB  - OBJECTIVE: To explore the causes of restenosis of the postoperative external
      auditory canal and the prevention of restenosis. METHOD: The clinical data of 27
      cases of external auditory canal stenosis in our hospital from January, 1997 to
      present were analyzed. RESULT: In our data, 27 cases of external auditory canal
      stenosis were treated by surgery. The restenosis had happened after the operation
      with a ratio of 25 percent. CONCLUSION: The precision selection of operative
      style and the lasting expanding of the external canal were important.

PMID- 15515560
TI  - [Postoperative morbidity of graft tympanic membrane in tympanoplasty and the
      relevant factors].
AB  - OBJECTIVE: To investigate the morbidity and configuration of graft (temporalis
      fascia) tympanic membrane as well as their pertinent factors in different stages
      after tympanoplasty so as to find out the measures to improve the graft
      morbidity. METHOD: 120 ears undergone tympanoplasty with medial graft techniques
      were observed. The postoperative grafts were followed up in 2 weeks, 1-3 months,
      4-6 months, 6-24 months and over 2 years respectively. The pertinent factors
      influencing the grafts growths and its functions were analyzed. RESULT: There
      were 4 grafts occurred crannies after 2 weeks, 2 cases occured infection in
      middle ear and had reperforation after 1-3 months, 24 cases with catheterization
      were found ineffective after 4-6 months and 13 grafts were found atrophy after 6
      months to 2 years followed up after operation respectively. There were total 10
      (8.33%) ears developed perforation again in 2 years. CONCLUSION: The cranny in
      anterioinferior border of the grafts is one of the main risky factor for the
      reperforation in new tympanic membrane in the early stage. The cases with severe
      pathosis in mucosa in tympanic cavity should be followed up intimately.
      Eustachian catheterization was one of the effective methods to the tubal
      dysfunction. The graft tympanic membrane function and configuration will become
      stabilized in three months postoperatively.

PMID- 15515561
TI  - [Study on the clearance function of mucociliary system in nasal middle meatus].
AB  - OBJECTIVE: To explore the clearance function of mucociliary system in nasal
      middle meatus. METHOD: The nasal middle meatus mucociliary transport rate (MTR)
      was measured by saccharin method in normal persons and patients with chronic
      suppurative sinusitis or chronic hypertrophic rhinitis or chronic simple
      rhinitis. The MTR in nasal common meatus were measured in persons as many as the
      people mentioned above with the same conditions. Samples of mucosa from nasal
      middle meatus in normal adults and patients with nasal polyps or chronic
      sinusitis were scanned by electron microscopy. RESULT: in healthy groups, the MTR
      of nasal middle meatus was (4.47 +/- 0.90) mm/min, and the MTR of nasal common
      meatus was(7.0 +/- 2.21) mm/min. There was significant difference between them (P
      < 0.01). The MTR of nasal middle meatus in patients groups were significantly
      lower than that in healthy groups (P < 0.01). In the patients groups, the MTR of
      nasal middle meatus were also lower than that of nasal common meatus and that in
      healthy groups. There were no difference between men and women. The electron
      microscopy scan showed that the cilias in nasal middle meatus distributed better
      in healthy persons than in patients. Some short cilias could be found, and the
      long cilias and the short cilias growthed alternately. CONCLUSION: MTR of nasal
      middle meatus is lower than that of nasal common meatus , so the protective
      function of mucociliary of nasal middle meatus is lower than that of nasal common
      meatus.

PMID- 15515562
TI  - [Clinical analysis of 6 cases with subarachnoid hemorrhage during transsphenoidal
      surgery for lesions of sellar region].
AB  - OBJECTIVE: To learn more about the rare application of subarachnoid hemorrhage
      (SAH) during transsphenoidal surgery (TSS) for lesions of sellar region. METHOD:
      Clinical statistics of 6 cases with SAH during TSS for lesions of seller region
      between 1964- 2001 was analyses. RESULT: 2 cases died and 4 cases were cured.
      CONCLUSION: The reason of SAH was from the residual tumor (2 cases) and from
      damaged sellar and arachnoidea. The doctor familiars the more with the anatomy of
      seller and skill of TSS, the complication decreases the more. Once SAH occurs,
      comprehensive treatment should be accepted.

PMID- 15515563
TI  - [The determination of endothelin in patients with bell palsy and its
      significances bell palsy and its significances].
AB  - OBJECTIVE: To detect the role of the plasma endothelin in the process of Bell
      palsy and its relationship to prognosis. METHOD: The plasma endothelin were
      respectively determined with radioimmunoassay in 21 patients with Bell palsy and
      20 normal control subjects. RESULT: The patients who were suffering from Bell
      palsy exhibited a statistically significant (P < 0.01) increase in the endothelin
      level compared with that in the 20 normal control subjects. A significantly
      higher level of the plasma endothelin was found in unsatisfactory recovery group
      compared with that in satisfactory recovery group. CONCLUSION: Endothelin may
      play an important role in the process of Bell palsy, and may be a useful marker
      for the assessment of prognosis to the patients.

PMID- 15515564
TI  - [Benign symmetric lipomatosis].
AB  - OBJECTIVE: To explore the clinical feature of benign symmetric lipomatosis (BSL)
      so as to improve its diagnosis and treatment. METHOD: 28 patients of BSL treated
      in our hospital were analyzed and literature was reviewed. Surgical management is
      used in all patients. RESULT: There were no patients died. All patients were
      satisfactory with their appearance and function improved. 28 patients were
      followed up for 2-15 years (average 6 years and 5 months), only 5 cases recurred.
      CONCLUSION: BSL usually occurs in middle age men. Patients have a striking
      appearance "hump back" because of a diffuse, symmetric distribution of the
      lipomatous tissue in the cervical region. The etiology is related to alcohol
      abuse. Operation is the most effective treatment. The radical surgical therapy
      should not be emphasized because the important anatomic structures may be
      damaged. Abstaining from alcohol may help to reduce the rate of recurrence.

PMID- 15515565
TI  - [Down-regulation of telomerase and its RNA and apoptosis in the HNE1 cell line of
      nasopharyngeal carcinoma induced by retinoid].
AB  - OBJECTIVE: To explore the down-regulation of telomerase as well as its RNA and
      apoptosis induced by retinoid acid. METHOD: After HNE1 cell lines of NPC were
      incubated with 10(-5) mol of retinoid in 6 days, the expression of telomerase and
      its RNA and the apoptosis of HNE1 cell lines were detected respectively with TRAP
      PCR ELISA, RT-nested PCR, apoptosis indexes and trans-electron microscope.
      RESULT: After 6 days when RA was added to the HNE1 cell line, the morphological
      change and suspending of HNE1 cells were found and the HNE1 cells reduced.
      Meanwhile, the expression of telomerase and hTR was obviously inhibited and the
      telomerase activity was only the 1/2 of the control with the use of ELISA
      indirect quantitative assay. Apoptosis indexes and apoptosis cells in RA groups
      were higher than those in control (P < 0.05). CONCLUSION: The expression of
      telomerase and hTR are obviously inhibited and the apoptosis of HNE1 cell lines
      is also induced by retinoid.

PMID- 15515566
TI  - [Observation on the effect of curettement-adhesive on submucous resection of
      nasal septum].
AB  - OBJECTIVE: To explore a method of how to handle the wound in submucous resection
      of nasal septum (SMR) so as to improve the effect of the operation. METHOD: 83
      cases with deviation of nasal septum underwent the operation of submucous
      resection of nasal septum. Then they were divided into two groups at random. One
      group as curettement-adhesive group (42 cases) were treated by biological
      adhesive solvent (BAS) to the wound after submucous resection of nasal septum
      without a tamping to the nasal cavity. The other group as control group (41
      cases) was treated by Vaseline gauze packing. Then the postoperative reactions
      and effect in each group were compared according to the degree of headache,
      hyperaemia of nasal mucosa and edema of nasal mucosa. RESULT: There were a
      distinct difference of the degree of headache, hyperaemia of nasal mucosa and
      effect in curettement-adhesive solvent group to the other group. CONCLUSION: The
      use of BAS in SMR can simplify the operation and shorten the rehabilitation time.
      It can relieve the postoperative reaction and reduce syndromes. So it is worth
      researching.

PMID- 15515567
TI  - [Clinical study of non-invasive nasal sinus mycoses].
AB  - OBJECTIVE: To explore the pathogeny, diagnosis and treatment of the noninvasive
      nasal sinus mycoses. METHOD: 11 cases with nasal sinus mycoses were analyzed
      retrospectively. All of them had undergone endoscopic operation. RESULT: After
      operation all cases got regular check up under endoscope. 9 cases recovered
      quickly. The other 2 had caseous matter in their maxillary sinus in the initial
      stage. After cleaning up the fungus ball and washing the maxillary sinus for
      several times, the surgical cavity became clear. 10 cases had been followed up
      for 6 months to 5 years and no recurrence occurred. The other one lost follow-up.
      CONCLUSION: Endoscopic operation is the basic surgical method to treat the non
      invasive nasal sinus mycoses. Excising the focus thoroughly, correcting the
      abnormal nasal cavity structure and resuming the cleanout function of nasal sinus
      cilia are the principle of treatment.

PMID- 15515568
TI  - [Methods of gene therapy for inner ear diseases].
AB  - OBJECTIVE: To study an effective, safety and convenient method for gene transfer
      and introduction to inner ear. METHOD: Ad GFP were transferred into inner ears of
      30 guinea pigs through round window, basal turn of cochlea and cerebrospinal
      fluid respectively. Auditory brainstem response (ABR)and otoacoustic emission of
      distortion products (DPOAE) were assayed to these animals preoperatively and
      postoperatively, then transfection and expression of Ad-GFP in inner ears and
      structure of cochlear hair cells were observed. RESULT: Transfection and
      expression of Ad-GFP were found in spiral ganglion of cochlea, stria vascularis
      and Cortisorgan through all of the three methods. The expression products were in
      the highest level at the third day after operation. But the operation through
      round window and basal turn of cochlea could lead to bleeding and coagulum
      deposited in parietalgyrus, which could result in hair cells injury. Changes of
      ABR threshold of these animals were not significant. But amplitude of DPOAE
      decreased significantly in animals through round window and basal turn of cochlea
      pathways. There was no hair cells injury and changes of DPOAE through
      cerebrospinal fluid pathway. CONCLUSION: The study suggested the operations
      through round window and basal turn of cochlea could lead to bleeding in
      cochleas, which resulted in change of DPOAE amplitude. It is a safe and effective
      method to transfer through cerebrospinal fluid.

PMID- 15515569
TI  - [The influence of medicine to the expression of cell adhesion molecule in
      experimental otitis media with effusion].
AB  - OBJECTIVE: To study the influence of Cefaclor and Prednisonum to the expression
      of cell adhesion molecule in experimental otitis media with effusion (OME).
      METHOD: SD rats models of OME were made using formalin killed nontypeable
      Hemophilus influenzae and the expression of adhesion molecules Mac-1 and L
      Selectin was analysed by flow cytometry using white blood cell obtained by
      cardiac puncture in control, bacterial and medicine groups. The pathology of
      middle ear mucosa was investigated to understand the relationship between the
      expression of adhesion molecules and the pathology. RESULT: It was found that the
      expression of adhesion molecules Mac-1 and L-Selection in bacteria group
      increased obviously with pathological change of the middle ear mucosa. Cefaclor
      and Prednisonum could decrease the expression of adhesion molecules and inhibited
      the leukocyte accumulation in the middle ear cavity though there was no
      significant differences except for the L-Selectin in the Cefaclor group between
      the bacteria group and the medicine group. CONCLUSION: Dead bacteria in the
      middle ear may act as an antigen to induce the inflammatory response and effusion
      of the middle ear. The expression of adhesion molecules Mac-1 and L-Selectin is
      highly related to the inflammatory response. Cefaclor and Prednisonum may improve
      otitis media with effusion, which may related to the decreasing expression of Mac
      1 and L-Selectin.

PMID- 15515570
TI  - [Clearance function of endolymphatic sac to extraneous TD-antigen].
AB  - OBJECTIVE: To study the clearance function of the rat endolymphatic sac to TD
      antigen. METHOD: 30 healthy adult S-D rats were employed in the experiment. At
      two weeks after being sensitized systemically with keyhole limpet hemocyanin
      (KLH) (Thymus-dependent antigen), the animals were inoculated into the labyrinth
      through cochlea base tune with the same antigen. At 1, 3 h, 1, 3,7 and 14 day
      after labyrinth vaccination, the rats were sacrificed and the temporal bones were
      removed, then the frozen-sections of the decalcified samples were examined
      respectively. Using Anti-KLH McAb, the SABC immunohistochemical methods were
      utilized to investigate the changes of KLH in the endolymphatic sac. RESULT: At 3
      h after labyrinth vaccination the antigen appeared in the endolymphatic sac.
      While the KLH were trapped and phagocytized in the endolymphatic sac at 1-7 day
      after labyrinth vaccination, the antigen in the cochleae gradually reduced. At
      the 14th day only feeble KLH positive stains can be found in the endolymphatic
      sac. CONCLUSION: The rat endolymphatic sac can phagocytize, dispose and removal
      extraneous antigen, which verifies the immune defense function of endolymphatic
      sac in inner ear immune response.

PMID- 15515571
TI  - Serum thymidine kinase activity: an alternative to histologic markers of cellular
      proliferation in canine lymphoma.
AB  - Thymidine kinase (TK) is a cellular enzyme which is involved in a 'salvage
      pathway' of DNA synthesis. It is activated in the G1/S phase of the cell cycle,
      and its activity has been shown to correlate with the proliferative activity of
      tumor cells.... Clinical studies have reported high serum TK concentrations in a
      variety of neoplasias. The majority of these studies concerned hematological
      malignancies. TK seems to be a useful marker in non-Hodgkin's lymphoma, where it
      correlates with clinical staging and provides marked prognostic information on
      (progression-free) survival.

PMID- 15515572
TI  - Bisphosphonates and cancer.
AB  - Bisphosphonates form a family of drugs characterized pharmacologically by their
      ability to inhibit bone resorption and pharmacokinetically by similar intestinal
      absorption, skeletal distribution, and renal elimination. Two groups of
      bisphosphonates exist chemically, non-amino-bisphosphates and amino
      bisphosphonates. The amino-bisphosphonates have greater antiresorptive
      capabilities and represent a newer generation of bisphosphonates. The primary
      mechanism of action of bisphosphonates is inhibition of osteoclastic activity.
      Non-amino-bisphosphonates are incorporated into the energy pathways of the
      osteoclast, resulting in disrupted cellular energy metabolism leading to
      apoptosis. Amino-bisphosphonates exert their effect on osteoclasts via their
      inhibition of the mevalonate pathways, resulting in disruption of intracellular
      signaling and induction of apoptosis. Bisphosphonates also inhibit cancer cell
      proliferation, induce apoptosis in in vitro cultures, inhibit angiogenesis,
      inhibit matrix metalloproteinase, have effects on cytokine and growth factors,
      and are immunomodulatory. Clinical applications in oncology could include therapy
      for hypercalcemia of malignancy, inhibition of bone metastasis, and therapy for
      bone pain. Although bisphosphonates are regarded as metabolically inert in the
      body, adverse effects do occur and include esophagitis, gastritis, suppression of
      bone repair, and allergic reactions. Little is published on the effects of
      bisphosphonates in dogs with cancer. Further research into the role of
      bisphosphonates in veterinary oncology is needed to identify clinical efficacy
      and safety of these potentially beneficial drugs.

PMID- 15515573
TI  - Doppler ultrasonographic evaluation of gastrointestinal hemodynamics in food
      hypersensitivities: a canine model.
AB  - Chronic enteropathy due to food hypersensitivity is a common complaint in dogs
      and humans, and definitive diagnosis and identification of offending allergens
      remains challenging. Doppler waveform analysis of the celiac artery (CA) and the
      cranial mesenteric artery (CMA) of 8 dogs with proven food hypersensitivity was
      performed in the fasting state and at 20, 40, 60, and 90 minutes after feeding
      their regular daily diet, and at 2 and 4 days after feeding 4 different
      allergens. Resistive index (RI), pulsatility index (PI), and the percentage
      differences between these measurements were calculated and compared
      statistically. The maximal decrease in RI and PI after feeding the regular diet
      was reached at 40 minutes after ingestion in both vessels (CA: RI = -6%, PI = 
      23%; CMA: RI = -9%, PI = -30%). After this trough, the resistance in both vessels
      rose nearly to baseline after 90 minutes (CA: RI = -1%, PI = -13%; CMA: RI = -3%,
      PI = -14%). When fed an allergen-containing meal the percentage changes at the
      trough were significantly greater (CA: RI = -10%, PI = -32%; CMA: RI = - 14%, PI
      = -40 %; p < 0.05) compared to those seen after feeding the maintenance diet.
      Also, RI and PI values were significantly (P < .05) lower at 90 minutes on days 2
      and 4 of the challenge period. During the challenge period, dogs did not show
      overt signs of gastrointestinal disease. Significant postprandial hemodynamic
      alterations in response to food allergens in dogs with food hypersensitivities
      can be shown noninvasively with Doppler ultrasound.

PMID- 15515574
TI  - Evaluation of plasma-ionized magnesium concentration in 122 dogs with diabetes
      mellitus: a retrospective study.
AB  - The goal of this study was to evaluate plasma-ionized magnesium (iMg2+)
      concentration in a large group of dogs with naturally occurring diabetes mellitus
      and to determine whether dogs with diabetes mellitus have hypomagnesemia, as
      reported in diabetic humans and cats. Plasma iMg2+ concentrations were
      retrospectively evaluated at the time of initial examination of 122 diabetic dogs
      at the Matthew J. Ryan Veterinary Hospital of the University of Pennsylvania.
      Diabetic dogs were defined as having uncomplicated diabetes mellitus (DM, 78
      dogs) diabetic ketoacidosis (DKA, 32 dogs), or ketotic nonacidotic diabetes
      mellitus (DK, 12 dogs) on the basis of presence or absence of metabolic acidosis
      or ketonuria. Twenty-two control dogs were used to determine reference values for
      plasma iMg2+ concentration in healthy dogs. Plasma iMg2+ concentration also was
      evaluated in 19 nondiabetic dogs with acute pancreatitis because many of the dogs
      with DKA had concurrent acute pancreatitis. Plasma iMg2+ concentration was
      significantly higher in dogs with DKA (median 0.41 mmol/L, reference range 0.14
      0.72 mmol/L) than in dogs with DM (0.33 mmol/L, 0.17-0.65 mmol/L; P = .0002) or
      the control group (0.32 mmol/L, 0.26-0.41 mmol/L; P = .006). There were no
      significant differences between plasma iMg2+ concentrations in dogs with DM or DK
      compared with control dogs. We conclude that dogs with naturally occurring
      diabetes mellitus do not have marked hypomagnesemia on initial examination at a
      tertiary care center.

PMID- 15515575
TI  - Free light-chain proteinuria and normal renal histopathology and function in 11
      dogs exposed to Lleishmania infantum, Ehrlichia canis, and Bbabesia canis.
AB  - The purpose of this retrospective study was to investigate the relationship among
      proteinuria consisting of immunoglobulin free light chains (FLCs), renal
      histopathologic findings, and routine markers of renal function in 11 dogs
      exposed to Leishmania infantum (n = 8), Ehrlichia canis (n = 2), and Babesia
      canis (n = 1). FLC proteinuria was suspected based on identification of a 22- to
      27-kDa band by sodium dodecyl sulfate-agarose gel electrophoresis (SDS-AGE) and
      later confirmed by immunofixation electrophoresis. SDS-AGE identified an isolated
      band of 22-27 kDa in 8 dogs, whereas the remaining 3 had a 22- to 27-kDa band and
      an additional band of 67-72 kDa. The median urine protein-to-urine creatinine
      ratio was 0.37 (range, 0.11-2.24) and increased ratios were found in 6 dogs
      (54.5%) (reference value, <0.7). All dogs underwent histologic examination of
      renal percutaneous biopsy specimens and determination of serum creatinine and
      urea concentrations. Tissue samples for light microscopy were stained with
      hematoxylin-eosin, periodic acid-Schiff, Goldners trichrome, and methenamine
      silver. In the study group, the glomerular tufts, mesangium, tubulointerstitium,
      and vessels appeared unaffected. The median serum creatinine concentration in
      these 11 dogs was 1.3 mg/dL (range, 0.8-1.5 mg/dL; reference range, 0.6-1.5
      mg/dL), whereas the concentration for urea was 28 mg/dL (range, 22-52 mg/dL;
      reference range, 20-50 mg/dL). All dogs had normal renal morphology and had
      normal serum creatinine and urea concentrations, suggesting that immunoglobulin
      FLC may be detected in the urine of dogs exposed to L. infantum, E. canis, and B.
      canis without any apparent structural or functional renal derangement.

PMID- 15515576
TI  - Plasma renin activity and plasma concentrations of aldosterone, cortisol,
      adrenocorticotropic hormone, and alpha-melanocyte-stimulating hormone in healthy
      cats.
AB  - A pathogenetic role of the renin-angiotensin-aldosterone system has been
      implicated in cats in both systemic arterial hypertension and hypokalemic
      myopathy. Yet, measurement of plasma aldosterone concentrations (PACs) and plasma
      renin activity (PRA) has not unequivocally pointed to hyperaldosteronism as a
      cause of these conditions. To obtain appropriate reference ranges, this study
      included a large number (130) of healthy house cats of different breeds without a
      history of recent illness and plasma concentrations of urea and creatinine below
      the upper limit of the respective reference ranges. In addition, the pituitary
      adrenocortical axis was studied by measuring plasma concentrations of
      adrenocorticotropic hormone (ACTH), alpha-melanocyte-stimulating hormone (alpha
      MSH), and cortisol. Reference ranges for PACs (110-540 pmol/L; 40-195 pg/mL), PRA
      (60-630 fmol/L/s; 0.3-3 ng/mL/h), and the aldosterone to renin ratio (ARR) (0.3
      3.8) were very similar to those established in the same laboratory for humans in
      a supine position. No breed differences were found. The ARRs in neutered cats
      were significantly higher than in intact cats, primarily because of low PRA in
      neutered cats. The ARRs of cats > or = 5 years of age were significantly higher
      than those of cats < 5 years of age. The plasma concentrations of ACTH, alpha
      MSH, and cortisol did not correlate significantly with PAC. Thus, although blood
      sampling was performed in cats in nonstandardized positions and was associated
      with a wide variation of stress responses, the references ranges of PAC, PRA, and
      ARR were similar to the relatively narrow limits established for humans under
      standardized conditions. The effects of neutering and aging on PRA and ARR
      warrant further investigation.

PMID- 15515577
TI  - Identification and characterization of an idiopathic pulmonary fibrosis-like
      condition in cats.
AB  - Interstitial lung diseases are a heterogeneous group of disorders with a variety
      of causes. In veterinary medicine, such lung diseases with a prominent fibrotic
      component of unknown etiology are often called idiopathic pulmonary fibrosis
      (IPF). In human medicine, this term is reserved for a distinct disease entity
      with specific histologic findings labeled as usual interstitial pneumonia (UIP).
      We identified 23 cats displaying histologic criteria of UIP The purpose of this
      retrospective study is to describe the presentation and response to therapy of
      these cats to better define this disease entity. All but 2 cats were middle aged
      to older (median 8.7 years), with no apparent sex or breed predisposition.
      Complaints included respiratory distress (n = 18) and cough (13). Duration of
      signs was less than 6 months in 17 cats. Physical-examination abnormalities
      included tachypnea, inspiratory or mixed inspiratory and expiratory effort, and
      adventitial lung sounds. No consistent hematologic or biochemical abnormalities,
      parasites, or positive serologic results for feline retroviruses, heartworms, or
      toxoplasmosis were present. Radiographic changes included dense patchy or diffuse
      interstitial, bronchiolar, and alveolar infiltrates. Analysis of bronchial lavage
      fluid revealed mild neutrophilic inflammation (n = 6) with no consistent pathogen
      growth. Clinical condition of 5 cats worsened after lavage. Coincident pulmonary
      neoplasia was identified in 6 cats. Response to therapy (corticosteroids,
      antibiotics, bronchodilators, and diuretics) was poor, and most cats died within
      days to months. Cats with histologic changes compatible with UIP had signs that
      mimicked many of the clinical findings of human IPF, and treatment response was
      similarly unrewarding.

PMID- 15515578
TI  - Complications associated with 355 flexible colonoscopic procedures in dogs.
AB  - Flexible colonoscopy is commonly performed in dogs with signs of large-bowel
      diseases. Although considered to be a safe procedure, no reports of complications
      associated with colonoscopy have appeared in the veterinary literature. The
      purpose of this study was to describe the frequency and types of adverse events
      that developed during flexible colonoscopy in dogs. Medical records were reviewed
      from 355 scheduled colonoscopic procedures. Major complications were defined as
      adverse events in which the dog's life was potentially jeopardized and the
      complication required intensive treatment or monitoring. Major complications
      consisting of fatal aspiration of GoLYTELY, colonic perforation, and excessive
      hemorrhage after biopsy of an adenocarcinoma with rigid forceps occurred in 3
      (0.85%) dogs. Minor complications associated with anesthesia or colonoscopy
      occurred during 3.4% of procedures. Complications were classified as minor if the
      adverse event required minimal treatment or monitoring, and the complication was
      not considered a threat to the dog's life. Vomiting of GoLYTELY occurred with the
      administration of 4.6% of doses in 6.5% of dogs. When administering GoLYTELY,
      clinicians should be prepared to rapidly remove the orogastric tube and mouth
      speculum if vomiting occurs to reduce the potential for aspiration. In this group
      of dogs undergoing flexible colonoscopy, major complications occurred
      infrequently and minor complications developed uncommonly. Overall, minor or
      major complications developed during 30 (8.5%) of 355 procedures. Mortality was
      rare (0.28%). Flexible colonoscopy appears to be a safe procedure in dogs with
      signs of large-bowel diseases.

PMID- 15515579
TI  - Association between liver copper concentration and subclinical hepatitis in
      Doberman Pinschers.
AB  - The prevalence of subclinical hepatitis was investigated in a group of 106
      randomly selected 3-year-old Doberman Pinschers. Histopathologic examination of
      liver samples from 65 dogs (52 dogs with high bile acids, alkaline phosphatase
      activity, or alanine aminotransferase activity or with copper granules in
      hepatocytes in a liver aspirate and 13 normal dogs) revealed subclinical
      hepatitis in 22 dogs (19 females and 3 males). Liver copper concentrations
      measured by instrumental neutron activation analysis was significantly higher
      (mean +/- SD; 419 +/- 414 microg/g dry matter) in dogs with hepatitis than those
      without liver disease (197 +/- 113 microg/g; P = .0008). At 2.6 +/- 0.6 years
      hepatitis persisted in 5 of 16 dogs available for examination. One dog with a
      high copper concentration but normal liver subsequently developed subclinical
      hepatitis after 3 years. During the follow-up period, the average copper
      concentration of the 6 dogs with persistent subclinical hepatitis was 939 +/- 299
      microg/g and had continued to rise significantly (P = .02). The hepatitis in
      these dogs was associated with apoptotic hepatocytes and copper-laden Kupffer
      cells in centrolobular regions. The results of this study suggest that there is a
      relationship among copper storage, hepatocellular damage, and hepatitis in
      Doberman Pinschers.

PMID- 15515580
TI  - Efficacy and safety of transdermal methimazole in the treatment of cats with
      hyperthyroidism.
AB  - The objective of this study was to determine whether transdermal methimazole was
      as safe and effective as oral methimazole for the control of hyperthyroidism in
      cats. Forty-seven cats with newly diagnosed hyperthyroidism were randomized to
      receive either transdermal methimazole in pluronic lecithin organogel (PLO;
      applied to the inner pinna), or oral methimazole (2.5 mg q12h for either route).
      Cats were evaluated at weeks 0, 2, and 4 with a physical exam, body weight
      determination, CBC, biochemical panel, urinalysis, measurement of total
      levothyroxine (T4) concentration, indirect Doppler blood pressure determinaiton,
      and completion of an owner questionnaire. Data between the 2 groups and over time
      were compared by nonparametric methods. Forty-four cats followed the protocol (17
      oral and 27 transdermal). Significantly more cats treated with oral methimazole
      had serum T4 concentrations within the reference range after 2 weeks (14 of 16
      cats) compared to those treated by the transdermal route (14 of 25; P = .027).
      This difference was no longer significant by 4 weeks of treatment (9 of 11 for
      oral versus 14 of 21 for transdermal), possibly because of inadequate numbers
      evaluated by 4 weeks. Cats treated with oral methimazole had a higher incidence
      of gastrointestinal (GI) adverse effects (4 of 17 cats) compared to the cats
      treated with transdermal methimazole (1 of 27; P = .04), but no differences were
      found between groups in the incidence of neutropenia, hepatotoxicity, or facial
      excoriations. Although the overall efficacy of transdermal methimazole is not as
      high as that of oral methimazole at 2 weeks of treatment, it is associated with
      fewer GI adverse effects compared to the oral route.

PMID- 15515581
TI  - Pulmonic stenosis in dogs: balloon dilation improves clinical outcome.
AB  - Medical records of 81 dogs with severe pulmonic stenosis from 2 referral centers
      were examined retrospectively. Forty dogs underwent balloon valvuloplasty (BV),
      which was performed by 1 operator, whereas 41 did not. The mean age at latest
      follow-up was 41.5 months. A statistical comparison of the clinical outcome and
      survival was performed. Dogs revealing clinical signs at presentation showed a 16
      fold increase in risk of death compared with asymptomatic dogs (P < .001).
      Statistical analyses demonstrated that an increase of 1 mm Hg in transstenotic
      pressure gradient (PG) at presentation was associated with a 3% increase in
      hazard rate (P < .001). Thirty-seven dogs survived BV with a median reduction in
      PG of 46%. The median preoperative PG was 120 mm Hg, and median PG 24 hours
      postoperatively was 55 mm Hg with a median of 55 mm Hg 6 months post-BV. Twenty
      (49%) of the non-BV (NBV) dogs remained asymptomatic at last follow-up. Fourteen
      (34%) of the NBV dogs died or were euthanized because of heart disease related to
      pulmonic stenosis. Twelve of these dogs died suddenly, whereas only 1 of the BV
      dogs died suddenly. After adjusting for PG, clinical signs at presentation, and
      age, BV or dilation was associated with a 53% reduction in hazard rate (P =
      .005). This study indicates that BV, when performed by an experienced operator,
      appears to be successful both in alleviating clinical signs and in prolonging
      survival in dogs with severe pulmonic stenosis.

PMID- 15515582
TI  - Pulmonary embolization of vascular occlusion coils in dogs with patent ductus
      arteriosus.
AB  - Transcatheter coil embolization of patent ductus arteriosus (PDA) was performed
      in 206 dogs between 1994 and 2003 at Texas A&M University, of which 7 (3%) had
      embolization of coils to the pulmonary vasculature. Thoracic radiographs
      indicated that coils were located in the right pulmonary artery in 6 of the 7
      dogs. Pulmonary perfusion scans were available for review in 5 dogs, and moderate
      perfusion defects were observed in the right caudal lung lobe in 4 dogs within 24
      hours of embolization. Perfusion deficits observed initially in 2 of the dogs
      resolved on perfusion scans performed at 6 months and 3.1 years. One dog did not
      have evidence of focal perfusion defects on a perfusion scan performed 4.5 months
      after embolization. All pulmonary embolizations occurred during the procedure.
      Attempts at retrieval of coils were unsuccessful in the 2 dogs in which it was
      attempted. No short- or long-term clinical complications were observed in any of
      the dogs with pulmonary embolization. We conclude that pulmonary embolization of
      vascular occlusion coils is an uncommon event and is not typically associated
      with adverse clinical effects in dogs with PDA.

PMID- 15515583
TI  - Echocardiographic estimation of mean left atrial pressure in a canine model of
      acute mitral valve insufficiency.
AB  - High mean left atrial pressure (MLAP) due to canine degenerative mitral valve
      disease is associated with clinically relevant morbidity and mortality. The
      ability to noninvasively measure MLAP would assist in the diagnosis and treatment
      of disease. Doppler echocardiography allows measurement of early transmitral
      blood flow (E) and the velocity of the mitral valve annulus (Ea). The ratio of
      early mitral inflow velocity to early mitral annular velocity (E: Ea) correlates
      well with MLAP in human subjects. We sought to determine the ability of E: Ea to
      predict MLAP in dogs with experimentally induced mitral regurgitation. Nine
      anesthetized purpose-bred dogs underwent placement of a Swan-Ganz catheter into
      the left atrium and recording of MLAP. Simultaneous transthoracic
      echocardiographic and hemodynamic studies were performed after acute chordae
      tendineae rupture and during IV infusion with nitroprusside (2.5-5.0 microg x kg(
      1) x min(-1)) or hydralazine (1-1.5 mg/kg). Mitral regurgitant fraction, measured
      by single-plane angiography and thermodilution, ranged from 17% to 81%. MLAP
      increased from 5.4 +/- 2.5 mm Hg to 17.4 +/- 9.4 mm Hg after creation of mitral
      valve regurgitation (MR; P = .018). Forty sets of echocardiographic measurements
      were obtained from 7 dogs, and E, as well as E: Ea, were linearly related to
      MLAP. The R2 value for the linear regression equation containing E: Ea as the
      dependent variable (0.83) was greater than that for E (0.73). The 95% confidence
      intervals were calculated for predicting MLAP = 20 mm Hg from E:Ea, and E:Ea >9.1
      or <6.0 indicated a 95% probability that MLAP was >20 mm Hg or <20 mm Hg,
      respectively. Echocardiography can be used to predict MLAP in isoflurane
      anesthetized dogs with experimentally induced acute mitral valve insufficiency.

PMID- 15515584
TI  - Inheritance of occipital bone hypoplasia (Chiari type I malformation) in Cavalier
      King Charles Spaniels.
AB  - Occipital bone hypoplasia with foramen magnum obstruction and secondary
      syringomyelia (SM) is a common condition in the Cavalier King Charles Spaniel
      (CKCS) that is similar to human Chiari type I malformation. A worldwide family
      tree of more than 5,500 CKCSs spanning a maximum of 24 generations was
      established by obtaining pedigree information from 120 dogs diagnosed with SM
      secondary to occipital bone hypoplasia. The ongoing study showed 6 of 8 great
      grandparents of all affected dogs could be traced back to 2 female ancestors so
      that all 8 were descended from one or the other or both. The disease appears to
      be more severe and have an earlier onset with increased inbreeding, especially
      when breeding from affected dogs. The family tree of idiopathic epilepsy (IE)
      appears to be a different subset of the CKCS population, although some overlap
      was observed. Idiopathic epilepsy is more frequent in lines originating from
      whole-color dogs. Selection for coat color is believed to have influenced the
      development of both occipital hypoplasia with secondary SM and IE. In addition,
      breeding guidelines to reduce the incidence of mitral valve disease have placed
      further pressures on the gene pool.

PMID- 15515585
TI  - Canine inflammatory myopathies: a clinicopathologic review of 200 cases.
AB  - A retrospective study was performed on 200 randomly selected cases of
      inflammatory myopathy in dogs from diagnostic muscle biopsies received at the
      Comparative Neuromuscular Laboratory, University of California, San Diego. The
      most common clinical signs in dogs diagnosed with an inflammatory myopathy were
      generalized weakness, stilted gait, dysphagia, masticatory or generalized muscle
      atrophy, inability to open the jaw, megaesophagus, and dysphonia. Myalgia was
      rarely described. Age of onset ranged from 0.25 to 14 years. Genders were equally
      represented. Breed distribution approximated the 2002 American Kennel Club
      registration statistics (r = .85) with the notable exception of Boxers and
      Newfoundlands. From the results of muscle biopsies, clinical signs, and presence
      or absence of antibodies against type 2M fibers, dogs were classified as a
      generalized inflammatory myopathy (gIM)--including immune-mediated polymyositis;
      infectious and preneoplastic myositis; and, rarely, dermatomyositislike or
      overlap syndromes or unclassified myositis-or a focal inflammatory myopathy (flM)
      -including masticatory muscle and extraocular myositis. Average creatine kinase
      (CK) and aspartate aminotransferase (AST) concentrations in gIMs were
      significantly higher than those with fIMs (P < .05). Neoplasia developed in 12 of
      200 dogs within 12 months of diagnosis of polymyositis, with lymphoma diagnosed
      in 6 of 32 Boxers. Inflammatory myopathy was associated with antibody titers
      against infectious diseases in 38 dogs. Neospora caninum and Hepatozoon
      americanum cysts were found in tissues of 2 dogs not serologically tested.
      Antibodies against an unidentified sarcolemmal antigen were found in 9 of 19
      Newfoundlands with polymyositis. The spectrum of canine inflammatory myopathies
      can be broad, with infectious etiologies relatively common, and can include
      preneoplastic and uncharacterized syndromes.

PMID- 15515586
TI  - Evaluation of body condition and weight loss in dogs presented to a veterinary
      oncology service.
AB  - Cancer cachexia is a well-recognized syndrome in human patients that is
      characterized by progressive involuntary weight loss. The prevalence of this
      syndrome in veterinary cancer patients is unknown. This study's objective was to
      investigate the occurrence of weight loss and cachexia, as characterized by body
      condition scoring, in dogs presented to a veterinary oncology service.
      Information collected on 100 dogs included signalment, diagnosis, weight at time
      of diagnosis, and, when available, weight from a time approximately 12 months
      before diagnosis. Body condition was assessed by using a 9-point system based on
      body silhouette and palpation of adipose tissue (4-5 = optimal, 1 = extreme
      cachexia, 9 = extreme obesity). Muscle wasting was scored based on palpation of
      skeletal muscle (3 = no wasting, 2 = mild, 1 = moderate, 0 = severe). Only 4% of
      the dogs exhibited cachexia as defined by a body condition score < or = 3,
      whereas 29% were classified as markedly overweight (> or = 7). Fifteen percent
      had evidence of clinically relevant muscle wasting (< or = 1). Body weight from a
      time before the diagnosis of cancer was available for 64 dogs. At the time of
      diagnosis, 31% had maintained or gained weight, 31% had lost up to 5%, 14% had
      lost between 5 and 10%, and 23% had lost >10% of body weight. Overall, the
      percentage of dogs with signs indicating a decline in nutritional status was less
      than what has been reported for human cancer patients. Future studies should
      investigate the extent to which weight loss occurs in canine patients on an
      appropriate plane of nutrition as well as to establish whether an association
      exists between poor nutritional status and outcome in canine cancer patients.

PMID- 15515587
TI  - Serum thymidine kinase activity in dogs with malignant lymphoma: a potent marker
      for prognosis and monitoring the disease.
AB  - Serum thymidine kinase (sTK) activity was evaluated as a tumor marker for canine
      malignant lymphoma (ML). The objective was to investigate if sTK, as in humans,
      could be used as a prognostic marker for survival time in dogs with ML and if sTK
      could identify early signs of progression of disease in treated dogs. Serum
      samples from 52 dogs with ML were tested for initial TK activity. Samples from 21
      normal dogs and 25 dogs with nonhematologic neoplasms were used for comparison.
      Forty-four dogs with ML were treated. Serum TK activity was measured in treated
      dogs before each treatment and every 4 weeks thereafter until relapse. Dogs with
      ML had 2-180 times higher TK activity (TK 5-900 U/L) than normal dogs (TK <7 U/L)
      based on the mean + 2 standard deviations. In the group of other neoplasms, only
      2 dogs had a moderate increase (6.4 and 7.5 U/L) compared with the controls. Mean
      sTK activities in the dogs with ML that had gone into complete remission (CR)
      were not significantly different from activities in healthy controls (P = .68).
      Mean sTK at least 3 weeks before and at the time of relapse was significantly
      higher than activity measured at CR (P < .0001). Dogs with ML that initially had
      sTK >30 U/L had significantly shorter survival times (P < .0001). Furthermore,
      sTK activity reflected the clinical staging of ML. Measuring sTK can be used as a
      powerful objective tumor marker for prognosis and for predicting relapse before
      recurrence of clinically detectable disease in dogs with ML undergoing
      chemotherapy.

PMID- 15515588
TI  - Chemotherapy followed by half-body radiation therapy for canine lymphoma.
AB  - A protocol of induction chemotherapy followed by half-body radiation therapy for
      treatment of lymphoma was used in 94 dogs. Seventy-three (78%) dogs achieved
      complete remission. Substage (P = .011) and phenotype (P = .015) were identified
      as predictors of complete remission rate. Of these, 52 dogs received half-body
      irradiation. Cranial and caudal halves received a total dose of 8.0 Gy, given in
      2 fractions of 4.0 Gy on consecutive days with cobalt-60 photons and a 3-week
      interval between halves. Median 1st remission for these dogs was 311 days. Anemia
      was identified as the only predictor for length of 1st remission (P = .024).
      Toxicoses after half-body irradiation generally were mild and infrequent and
      included myelosuppression and gastrointestinal signs. Thirty-one dogs relapsed
      and 20 resumed treatment with induction followed by maintenance chemotherapy.
      Seventeen (85%) dogs achieved a 2nd complete remission. Median overall remission
      for all 52 dogs was 486 days. Results of this study suggest that half-body
      radiation therapy after induction chemotherapy is well tolerated and might
      increase remission duration compared with conventional protocols that use
      chemotherapy alone, but this increase might not be long enough to be clinically
      relevant or to justify application of the method described herein.

PMID- 15515589
TI  - Flow cytometric immunophenotype of canine lymph node aspirates.
AB  - Increasing availability of reagents able to distinguish subtypes of lymphocytes
      and other leukocytes has enabled greater understanding of lymphocyte biology and
      pathology in the dog. Lymphocytes in circulation most commonly are subjected to
      immunophenotypic assessment by flow cytometry, but needle aspirates of lymph
      nodes can be similarly suitable for immunophenotypic examination. In this
      investigation, the feasibility of immunophenotyping samples obtained by needle
      aspiration of lymph nodes from 32 dogs with no physical abnormalities and 6 dogs
      with lymphoma was determined. In addition, samples from 6 dogs were stored
      overnight at 4 degrees C and reanalyzed 24 hours later. For each sample, stained
      smear preparations were examined microscopically for lymphocyte morphology,
      neoplasia, and the presence of inflammatory cells. Expression of antigens on a
      corresponding sample of aspirated cells was determined by flow cytometric
      detection of antibody binding on a minimum of 10,000 events. The distribution of
      data was determined with Anderson-Darling tests, and reference intervals
      incorporating the central 95% of values were established. Adequate samples were
      obtained from 30 of 32 clinically normal dogs. Immunophenotypic results after 24
      hours of storage were consistent with those obtained immediately after sampling.
      Reference intervals for lymphocyte subsets from normal dog lymph nodes were
      similar to the proportions of CD3+, CD4+, CD8+, and CD21+ lymphocytes found in
      blood. Aspirates of enlarged lymph nodes from dogs with lymphoma were readily
      classified by this technique. Aspiration of lymph nodes from dogs for
      comprehensive analysis by flow cytometry is feasible and applicable to
      immunophenotyping of lymphoma.

PMID- 15515590
TI  - Pulmonary ultrasonographic abnormalities associated with naturally occurring
      equine influenza virus infection in standardbred racehorses.
AB  - The purpose of this investigation was to determine if naturally occurring acute
      infectious upper respiratory disease (IRD) caused by equine influenza virus is
      associated with ultrasonographically detectable pleural and pulmonary
      abnormalities in horses. Standardbred racehorses were evaluated for signs of IRD,
      defined as acute coughing or mucopurulent nasal discharge. For every horse with
      IRD (n = 16), 1 or 2 horses with no signs of IRD and the same owner or trainer (n
      = 30) were included. Thoracic ultrasonography was performed within 5-10 days of
      the onset of clinical disease in horses with IRD. Horses without IRD were
      examined at the same time as the horses with IRD with which they were enrolled.
      The rank of the ultrasound scores of horses with IRD was compared to that of
      horses without IRD. Equine influenza virus was identified as the primary
      etiologic agent associated with IRD in this study. Mild lung consolidation and
      peripheral pulmonary irregularities were found in 11 (69%) of 16 of the horses
      with IRD and 11 (37%) of 30 of control horses. Lung consolidation (median score =
      1) and peripheral irregularities scores (median score = 1) were greater in horses
      with IRD compared to horses without IRD (median score = 0; P < .05). Pleural
      effusion was not observed. Equine influenza virus infection can result in
      abnormalities of the equine lower respiratory tract. Despite the mild nature of
      IRD observed in this study, lung consolidation and peripheral pulmonary
      irregularities were more commonly observed in horses with clinical signs of IRD.
      Further work is needed to determine the clinical significance of these
      ultrasonographic abnormalities.

PMID- 15515591
TI  - Pharmacokinetics of once-daily amikacin in healthy foals and therapeutic drug
      monitoring in hospitalized equine neonates.
AB  - The objectives of this study were to investigate the pharmacokinetics of once
      daily amikacin in healthy neonates, to determine amikacin concentrations in
      hospitalized foals, and to determine the minimum inhibitory concentrations (MICs)
      of amikacin against gram-negative isolates from blood cultures in septic foals.
      Median half-life, clearance, and volume of distribution of amikacin in healthy 2-
      to 3-day-old foals after administration of an intravenous bolus of amikacin (25
      mg/kg) were 5.07 hours (4.86-5.45 hours), 1.82 mL/min/kg (1.35-1.97 mL/min/kg),
      and 0.785 L/kg (0.638-0.862 L/kg), respectively. Statistically significant (P
      <.05) decreases in area under the curve (14% decrease), mean residence time (19%
      decrease), and C24h plasma amikacin concentrations (29% decrease) occurred
      between days 2-3 and 10-11. Plasma amikacin concentrations in healthy foals at
      0.5 hours (C0.5h) were significantly higher (P = .02) than those of hospitalized
      foals. Sepsis, prematurity, and hypoxemia did not alter amikacin concentrations.
      The MIC at which 90% of all gram-negative isolates from equine neonatal blood
      cultures were inhibited by amikacin was 4 microg/mL, suggesting that amikacin
      C0.5h of 40 microg/mL should be targeted to achieve a maximum serum concentration
      to MIC ratio of 10:1. The proportion of foals with C0.5h 40 microg/mL was
      significantly higher (P < .0001) in hospitalized foals receiving a dose of
      amikacin at 25 mg/kg (22/24 or 92%) than in foals receiving a dose at 21 mg/kg
      (9/25 or 36%), whereas no difference was found in the proportion of foals with
      C24h concentrations > or = 3 microg/mL between the 2 groups. An initial dose at
      25 mg/kg is recommended for once-daily amikacin in equine neonates.

PMID- 15515592
TI  - Experimental Clostridium difficile enterocolitis in foals.
AB  - Despite empirical clinical association of infection with Clostridium difficile
      with colitis in horses, a causal link has not been confirmed. The objective of
      this study was to develop a model of C. difficile-associated diarrhea in foals
      with normal transfer of passive immunity. Nine 1-day-old pony foals were
      inoculated intragastrically with spores or vegetative cells of C. difficile. Five
      foals were challenged with spores, with 2 receiving 10(5) colony-forming units
      (CFUs) and concurrently 3 receiving 10(7) CFUs once daily for 3 days. Clindamycin
      was administered orally to disrupt gastrointestinal flora. A further 4 foals were
      challenged by orogastric administration of 10(10) CFUs of vegetative cells once
      daily for 3 days or until diarrhea developed. This group did not receive
      clindamycin. Spore and vegetative cell preparations were negative for toxins of
      C. difficile and common enteropathogens. Clinical signs varied from mild
      abdominal discomfort and pasty feces to colic and watery diarrhea in 8 of 9
      foals. Four of 5 foals challenged with spores developed mild diarrhea, whereas
      all foals challenged with vegetative cells developed moderate to severe diarrhea.
      C. difficile was isolated from feces of all foals between 24 and 72 hours after
      inoculation and toxins A or B or both were detected in the feces of all foals by
      an enzyme-linked immunosorbent assay. We concluded that spores and vegetative
      cells of C. difficile are capable of colonizing the gastrointestinal tract,
      producing toxins, and inducing clinical signs similar to those encountered in
      naturally occurring cases. This study fulfilled Koch's postulates for C.
      difficile-associated diarrhea in foals and provides a model for consistent
      reproduction of the disease for future studies.

PMID- 15515593
TI  - Pharmacokinetics and pharmacodynamics of furosemide after oral administration to
      horses.
AB  - Furosemide is the most common diuretic drug used in horses. Furosemide is
      routinely administered as IV or IM bolus doses 3-4 times a day. Administration PO
      is often suggested as an alternative, even though documentation of absorption and
      efficacy in horses is lacking. This study was carried out in a randomized,
      crossover design and compared 8-hour urine volume among control horses that
      received placebo, horses that received furosemide at 1 mg/kg PO, and horses that
      received furosemide at 1 mg/kg IV. Blood samples for analysis of plasma
      furosemide concentrations, PCV, and total solids were obtained at specific time
      points from treated horses. Furosemide concentrations were determined by reversed
      phase high-performance liquid chromatography with fluorescent detection. Systemic
      availability of furosemide PO was poor, erratic, and variable among horses.
      Median systemic bioavailability was 5.4% (25th percentile, 75th percentile: 3.5,
      9.6). Horses that received furosemide IV produced 7.4 L (7.1, 7.7) of urine over
      the 8-hour period. The maximum plasma concentration of 0.03 microg/mL after
      administration PO was not sufficient to increase urine volume compared with
      control horses (1.2 L [1.0, 1.4] PO versus 1.2 L [1.0, 1.4] control). There was a
      mild decrease in urine specific gravity within 1-2 hours after administration of
      furosemide PO, and urine specific gravity was significantly lower in horses
      treated with furosemide PO compared with control horses at the 2-hour time point.
      Systemic availability of furosemide PO was poor and variable. Furosemide at 1
      mg/kg PO did not induce diuresis in horses.

PMID- 15515594
TI  - D-lactate production and excretion in diarrheic calves.
AB  - The origin of D-lactate, the most important acid contributing to metabolic
      acidosis in the diarrheic calf, is unknown. We hypothesized that because D
      lactate is produced only by microbes, gastrointestinal fermentation is the
      source. The objective of this study was to determine whether D-lactate production
      occurs in the rumen, colon, or both, and to measure D- and L-lactate
      concentrations in urine. Fecal, rumen, blood, and urine samples were obtained
      from 16 diarrheic and 11 healthy calves. Serum electrolyte concentrations were
      measured in both groups, and blood gas analyses were performed for diarrheic
      calves. All samples were analyzed for D- and L-lactate by high performance liquid
      chromatography (HPLC). Diarrheic calves were generally hyperkalemic with high
      serum anion gap, depressed serum bicarbonate, and low blood pH. L-lactate was
      markedly higher in rumen contents (22.7 mmol/ L [median]) and feces (8.6 mmol/L)
      of diarrheic calves than healthy calves (0.5 mmol/L and 5.1 mmol/L,
      respectively), but not different in serum or urine. Rumen, fecal, serum, and
      urine D-lactate concentrations were all significantly higher (P < .05) in
      diarrheic calves (17.0, 25.4, 13.9, and 19.2 mmol/L, respectively) than in
      healthy calves (0.5, 9.1, 1.4, and 0.5 mmol/L, respectively). Higher D-lactate
      concentrations in the rumen and feces of diarrheic calves suggests these sites as
      the source of D-lactate in blood and urine.

PMID- 15515595
TI  - Chromophobe adenocarcinoma of the pituitary gland in a ram.

PMID- 15515596
TI  - Diagnosis of aorto-iliac thrombosis in a quarter horse foal using Doppler
      ultrasound and nuclear scintigraphy.

PMID- 15515597
TI  - Bronchiectasis in three adult horses with heaves.

PMID- 15515598
TI  - Atypical acute monensin toxicosis and delayed cardiomyopathy in belgian draft
      horses.

PMID- 15515599
TI  - Fibrocartilaginous embolic encephalomyelopathy of the brainstem and midcervical
      spinal cord in a dog.

PMID- 15515600
TI  - Evolution of a B-cell lymphoma to multiple myeloma after chemotherapy.

PMID- 15515601
TI  - Echocardiography in the chinchilla.
AB  - Heart disease has been described in the chinchilla and, with increasing
      popularity as a pet, the demand for diagnostic evaluation and treatment has
      increased. The goal of this study was to determine reference values for
      echocardiographic measurements in chinchillas and the effect of anesthesia on
      these measurements. Seventeen clinically healthy adult chinchillas were studied.
      All animals were anesthetized with isoflurane by mask. Standard echocardiographic
      views were used. A difference was seen in the echocardiographic measurements for
      left ventricular systolic dimension, fractional shortening, aortic (Ao) diameter,
      left atrial (LA) diameter, ratio of LA diameter to Ao diameter, and peak flow
      velocities and ejection times for Ao and pulmonary artery flows between awake and
      anesthetized chinchillas.

PMID- 15515602
TI  - Profile: Joe Teaff, DDS. Interview.

PMID- 15515603
TI  - Profile: Scott Adkins, ODA contract lobbyist. Interview.

PMID- 15515604
TI  - Antibiotics for your computer?

PMID- 15515606
TI  - Face of the volunteer.

PMID- 15515605
TI  - 2004 ODA legislative report.

PMID- 15515607
TI  - Every dentist is a sculptor.

PMID- 15515608
TI  - Allocate your assets to offset market swings.

PMID- 15515609
TI  - Oral pathology case. Granular cell tumor. .

PMID- 15515610
TI  - Laparoscopic treatment of Barrett's esophagus.

PMID- 15515611
TI  - Treatment of retroperitoneal sarcomas.

PMID- 15515612
TI  - Laparoscopic ventral hernia repair.

PMID- 15515613
TI  - Maintenance of surgical competence: new requirements for the new millennium.

PMID- 15515614
TI  - Surgery in the elderly: the evolving role of palliative care in general surgical
      practice.
AB  - Palliative care will continue to be an evolving part of general surgical
      practices, especially with an expanding elderly population. The challenge to a
      surgeon remains, namely, understanding when palliation is a better alternative to
      aggressive therapeutic measures. The transition from curative intervention to
      palliative care is aided by honest communication between physician and patient
      and respect for dying with dignity. An intimate understanding of the
      multidimensional nature of palliative care will enable a surgeon to provide
      appropriate care for a terminal patient.

PMID- 15515615
TI  - Minimally invasive esophagectomy.

PMID- 15515616
TI  - Surgical management of cutaneous melanoma: current practice and impact on
      prognosis.

PMID- 15515617
TI  - The current role of sentinel node biopsy in the treatment of breast cancer.

PMID- 15515618
TI  - Symptomatic hemorrhoids.
AB  - The most important aspect in the diagnosis of hemorrhoidal disease is the
      exclusion of other, more life-threatening conditions. Hemorrhoidal banding
      remains the most successful method to manage hemorrhoids in the outpatient
      clinic. Chronic application of local medications to the perineum may result in
      dermatologic conditions. It is safe to manage acutely inflamed hemorrhoids
      surgically. Table 1 is a summary of the various methods for the surgical
      management of symptomatic prolapsing hemorrhoids. Dietary manipulation, including
      fiber supplementation, should always accompany surgical

PMID- 15515619
TI  - The role of endoluminal stents in gastrointestinal diseases.

PMID- 15515620
TI  - Current status of thoracoabdominal aneurysm repair.

PMID- 15515621
TI  - Treatment of asymptomatic carotid stenosis with contralateral carotid occlusion.

PMID- 15515622
TI  - Ten years' experience treating abdominal aortic aneurysms with stent-grafts.
AB  - Stent-graft therapy for aortic aneurysms is a valuable alternative to open aortic
      repair, especially in older, sicker patients with large aneurysms. Continued
      device improvements coupled with an enhanced understanding of the important role
      of aortic pathology in determining therapeutic success will eventually permit
      ESGs to be a more durable treatment for aortic aneurysms.

PMID- 15515623
TI  - The treatment of acute embolic lower limb ischemia.

PMID- 15515624
TI  - Duodenal switch operation for morbid obesity.

PMID- 15515625
TI  - Ileal-pouch anal restorative proctocolectomy for ulcerative colitis.

PMID- 15515627
TI  - Surgical therapy for hepatocellular carcinoma.

PMID- 15515626
TI  - Minimal access surgical approaches in infants and children.

PMID- 15515628
TI  - Radioguided Parathyroid surgery.

PMID- 15515629
TI  - Overview: the state of head lice management and control.
AB  - Head lice infestations affect millions of people in the United States. Children
      become infested more often than adults and account for the largest percentage of
      infestations. Head lice have not been shown to transfer disease, and they are not
      associated with serious morbidity. The most common effect of lice infestation is
      pruritus of the scalp with occasional cutaneous infection caused by scratching.
      Nevertheless, many schools have "no-nit" policies, which require the dismissal of
      children from school if nits or lice are found. These policies are ineffective in
      preventing infestations and result in many missed days of school. Lice
      infestations are most effectively managed with pediculicides. Pyrethroids are the
      mainstay of over-the-counter products. Prescription pediculicides include OVIDE
      (malathion) Lotion, 0.5% and lindane (formerly marketed as Kwell). Resistance to
      pyrethroids due to misuse and overuse has been documented. Lindane resistance
      also has been reported, and serious safety issues about lindane have been raised
      by the Food and Drug Administration. Lindane labeling now includes warnings and
      several restrictions in its use. Malathion is not associated with major systemic
      safety issues or the development of resistance within the United States. A
      contributor to pediculicide resistance is misdiagnosis of lice infestations.
      Survey data reveal frequent misdiagnosis of infestations in children who do not
      have live lice. Physicians generally are more likely to misdiagnose infestations
      than nonhealthcare providers. Misdiagnosis contributes to resistance by causing
      overuse, and consequently overexposure, of pediculicides. These agents should be
      used only if live lice or viable nits are discovered. Head lice infestations
      generally do not contribute to health risks for individuals or the public. The
      most serious consequence is the social cost of missed school days and the
      associated cost of lost productivity and wages of parents who must care for
      children sent home from school. Better diagnosis, more appropriate use of
      pediculicides, and elimination of no-nit policies will improve the overall
      management of head lice infestations.

PMID- 15515630
TI  - Clinical update on resistance and treatment of Pediculosis capitis.
AB  - The anatomy and physiology of head lice make them extremely adaptable to their
      human hosts but also difficult to eradicate. Their coloring and small size make
      them difficult to see, and the larvae, or nymphs, have multiple exoskeletons for
      protection. When exposed to pediculicides, a nymph can shed its outer exoskeleton
      and receive only a sublethal dose. Through natural selection, head lice have
      developed resistance to commonly used pediculicides, making it increasingly
      difficult to eliminate infestations. Other contributors to resistance include
      changes in formulations of pediculicides and improper use. Over the last 20
      years, the efficacy of pyrethrins has declined because of necessary safety
      changes in formulations and unintentional effects of new packaging on chemical
      components of these products. Pediculicides designed to be applied to wet hair
      may become too diluted to produce the desired effect. Patients also may use too
      little product to conserve costs. The combination of decreased product efficacy
      and exposure of head lice to diluted or insufficient amounts of pediculicides has
      reduced their effectiveness substantially. Studies comparing the current efficacy
      of several over-the-counter and prescription pediculicides with effectiveness in
      the 1980s has shown that OVIDE (malathion) Lotion, 0.5% is the only product that
      has retained its efficacy over time. The efficacy of over-the-counter pyrethrin
      products had declined significantly, and lindane, another prescription product,
      was least effective of all products tested both in the 1980s and in more recent
      studies. In addition to retaining its efficacy, malathion 0.5% also is effective
      when applied for only 20 minutes. The shorter application time is safer for
      children and also decreases the likelihood that residual product remains in the
      hair, further contributing to resistance.

PMID- 15515631
TI  - American Academy of Pediatrics guidelines for the prevention and treatment of
      head lice infestation.
AB  - The American Academy of Pediatrics (AAP) established diagnosis and treatment
      guidelines for pediculosis in 2002. Ideally, diagnosis should be based on the
      observation of a live louse. The presence of nits is also used by many people to
      positively diagnose an infestation, although a nit located farther from the scalp
      than 1 cm is unlikely to be viable. Other material on the scalp may be mistaken
      for nits, leading to misdiagnosis. Because lice are not associated with serious
      medical problems, the primary consideration of the AAP regarding treatment is the
      safety of pediculicides and other products used to treat head lice. From a
      pediatrician's perspective, no significant risk is acceptable. Over-the-counter
      (OTC) pyrethroid products (pyrethrin and permethrin) are commonly used by parents
      to treat their children and are generally considered safe for most people.
      Pyrethroids are not completely ovicidal, however, so a second application is
      required. Misuse and overuse of these products have contributed to the
      development of resistance. Prescription products include permethrin 5%, lindane,
      and malathion 0.5%. Resistance to permethrin 5% and lindane has been documented.
      In addition, lindane is associated with serious adverse events and should be used
      with caution only in a select population. Malathion 0.5% is about 98% ovicidal,
      and no resistance has been reported. Malathion is highly effective, but AAP
      guidelines note that the product is flammable and serious adverse effects can
      occur with ingestion. Very few cases of ingestion have occurred, and no reported
      cases of flammability, but children being treated with malathion should be
      carefully supervised, and this pediculicide should not be used unless treatment
      with OTC products has failed. AAP guidelines also state that no-nit policies in
      schools are detrimental, causing lost time in the classroom, inappropriate
      allocation of the school nurse's time for lice screening, and a response to
      infestations that is out of proportion to their medical significance. Accurate
      diagnosis, safe treatment options, and a common-sense approach to managing
      infestations in schools are recommended.

PMID- 15515632
TI  - Treating and managing head lice: the school nurse perspective.
AB  - School nurses often are the first healthcare professionals to diagnose lice
      infestations in children. Although lice do not transmit disease, many schools
      send children home if they detect live head lice. It is the position of the
      National Association of School Nurses that children who have been treated for
      lice infestations should not be excluded from school because of the presence of
      residual nits. The primary goals of the school nurse in controlling infestations
      are to identify children with head lice and to break the cycle of reinfestation.
      Routine screening of children for head lice is often part of infestation
      management policies in school districts. A thorough screening of a child's head
      can take several minutes. If a school's policy is to screen all students, the
      total time for examination adds significantly to the school nurse's caseload. The
      use of the school nurse's time for universal screening must be measured against
      other responsibilities, including health problem management, medication
      management, health assessments, and vision and hearing screening. Once a child is
      identified as having lice, the school nurse can play a key role in working with
      the child's family to eradicate the infestation. Education about treatment
      options and environmental cleaning are topics the nurse can address with the
      family. The school nurse also can function as a case manager who coordinates
      various aspects of treatment for an affected child. Because infestations can be
      very upsetting to students and to their families, the nurse can provide support
      and reassurance to the family as the child is treated. Participation of school
      nurses in developing appropriate and consistent policies and procedures within
      the school district is vital to the overall management of infestations. Their
      efforts to control and reduce infestations are necessary for the overall health
      of the school population.

PMID- 15515633
TI  - Head lice treatment costs and the impact on managed care.
AB  - The number of head lice infestations occurring annually in the United States is
      estimated at 6 million to 12 million. Although a formal economic analysis of head
      lice treatments has not been conducted, the direct cost of treatment can be
      roughly estimated by considering the costs of pediculicides and taking into
      consideration that patients may self-treat up to 5 times before seeking medical
      care. Added to the direct costs of treatment are indirect costs because of lost
      school days and lost productivity and wages of parents who must stay home to care
      for children who are sent home from schools that employ no-nit policies. The cost
      of head lice infestation is tied to diagnostic and treatment practices. Research
      suggests that head lice infestations are frequently misdiagnosed. In addition,
      over-the-counter treatments are often used incorrectly. The combination of
      misdiagnosis and improper treatment has contributed to decreased efficacy of
      pediculicides. This, in turn, further contributes to ineffective treatment and
      the necessity for retreatment and related increases in costs. Lindane, a
      prescription pediculicide, is associated with serious safety concerns and is now
      recommended for use in selected populations only when conventional treatment
      fails. Malathion 0.5% is the only prescription pediculicide that is considered to
      be safe and effective with no decrease in efficacy over time. Managed care
      organizations, in collaboration with school nurses and other healthcare
      providers, are working to promote more accurate diagnosis and proper use of
      pediculicides. The objectives of these efforts are to make the treatment of head
      lice more effective and ultimately to lower the cost of treatment by introducing
      better options early on.

PMID- 15515634
TI  - Faculty discussion: definitive management of head lice in the era of pediculicide
      resistance.

PMID- 15515635
TI  - Health service costs of paediatric cochlear implantation: influence of the scale
      and scope of activity.
AB  - The health service cost of paediatric cochlear implantation (CI) varies among
      hospitals in the UK. The purpose of this study was to determine whether the
      variation is associated with differences in the scale and scope of activity in CI
      programmes. The health service cost of CI was estimated for 908 children
      implanted in 12 hospitals between 1989 and 1998. Annual levels of activity in
      implanting children and adults were monitored in the same hospitals. Costs of
      paediatric CI were lower in hospitals implanting larger numbers of children and
      adults, thereby benefiting from economies of scale and scope, respectively. These
      economies arose from lower per-child staff costs in larger programmes, and were
      estimated to be exhausted when a hospital implanted more than nine children and
      more than 20 adults each year. Accommodating increased numbers of children in an
      existing programme is predicted to cost less than setting up a new programme.

PMID- 15515636
TI  - Estimations of auditory sensitivity for young cochlear implant candidates using
      the ASSR: preliminary results.
AB  - This paper presents preliminary results obtained with the use of the auditory
      steady-state response (ASSR) technique as part of a cochlear implant candidacy
      assessment protocol for infants Fifteen infants (30 ears), between 10 and 60
      months of age, with severe-to-profound hearing loss participated in the study.
      ASSR measurements were performed for 0.5, 1, 2 and 4kHz at intensities up to 120
      128dB HL. The ASSR thresholds were obtained in 74%, of the measurements, and
      exceeded the maximum auditory brainstem response (ABR) intensity output in 91% of
      cases and the maximum free-field behavioral intensity output in 84% of cases.
      Eighty-seven per cent of ASSR threshold measurements were measured at intensities
      of 100dB HL or higher, and almost half (47%) were measured at intensities of 115
      dB HL and higher. Preliminary results indicate that absent ABR and behavioral
      thresholds do not preclude the possibility of residual hearing, making the ASSR a
      primary source of information regarding profound levels of hearing loss.

PMID- 15515637
TI  - Psychosocial work environment, hearing impairment and health.
AB  - This article summarizes results from a study of hearing-impaired men and women in
      the labour force in Sweden. A questionnaire about psychosocial work environment
      (in accordance with the Demand-Control Model), health and wellbeing was sent out
      and answered by 445 hearing-impaired people, 20-64 years of age. A large
      reference group had previously answered the same questionnaire. The results
      indicate that imbalances between demand and control (i.e. high demand and low
      control, so-called high stress work type) is more common among hearing-impaired
      people than in the reference group. The outcome of the combination high demand
      and low control among hearing-impaired people is (much) worse than among hearing
      impaired people with other work types (passive. active, low stress). Hearing
      impaired people with the high-stress work type more frequently report bad
      physical health status and psychological wellbeing regarding a number of
      indicators There is, moreover, a tendency for women to be worse off than men. Our
      data suggest that those involved in audiological rehabilitation should pay great
      attention to hearing-impaired people with jobs that can be characterized as high
      stress.

PMID- 15515638
TI  - Outcomes of hearing aid fitting for older people with hearing impairment and
      their significant others.
AB  - As hearing impairment affects communication, it seems intuitive that both the
      person with hearing impairment and the significant other (SO) will experience
      effects as a result of the impairment and subsequent rehabilitation. The present
      study examined the effect that hearing impairment and aural rehabilitation has on
      the person with hearing impairment and the SO's quality of life (QOL). Ninety
      three people with hearing impairment completed a measure of hearing-specific QOL
      (Hearing Handicap Inventory for the Elderly) and health-related QOL (Short Form
      36), while 78 SOs completed a modified version of the Quantified Denver Scale and
      the Short Form-36, prior to and 3 months following hearing aid fitting. The
      results emphasize the significant impact of hearing impairment on both the person
      with hearing impairment and the SO. The results also demonstrate the effective
      role that hearing aids play in reducing such negative effects for both parties.

PMID- 15515639
TI  - The effect on speech intelligibility of varying compression time constants in a
      digital hearing aid.
AB  - The identification of nonsense syllables in quiet and in three types of
      background (babble, cafeteria and single female speaker) was measured using four
      hearing aid compression algorithms differing in attack and release time
      constants, and using linear amplification. The speech level was always 65 dB SPL.
      The compression algorithms, which were implemented in a Phonak Claro ITE hearing
      aid, were: (1) 'very fast'--the attack time was 8 ms and the release time was 32
      ms, for all 20 channels; (2) 'slow-fast'--the attack and release times decreased
      from 500 ms for low frequencies to about lOOms for high frequencies; (3) 'fast
      slow'-the attack and release times increased from about 50ms for low frequencies
      to 500 ms for high frequencies; and (4) 'slow + fast'-a very slow-acting gain
      control signal was combined with a fast-acting gain control signal, for each
      channel in a 10-channel system. Acoustical stimuli were presented monaurally via
      a circumaural headphone mounted over the hearing aid. The linear condition did
      not use the Claro aid; instead, the signal was digitally filtered to implement
      the Cambridge formula prior to delivery via the earphone. Five subjects with
      moderate sensorineural hearing loss were tested in a counter-balanced order
      across conditions. In quiet, performance was best for linear amplification and
      worst for the slow + fast algorithm. In the presence of background sounds, the
      highest scores were obtained with the linear-gain Cambridge formula implemented
      via headphones; a supplementary experiment suggested that this was due to the
      greater high-frequency gain resulting from the use of this formula. No
      significant differences were found between scores for the different compression
      algorithms. We conclude that the intelligibility of speech at a fixed level,
      presented in background sounds, is not markedly affected by rather substantial
      variations of the time constants in a multichannel compression system.

PMID- 15515640
TI  - A questionnaire study of the quality of life and quality of family life of
      individuals complaining of tinnitus pre- and post-attendance at a tinnitus
      clinic.
AB  - Tinnitus is a condition that is difficult to treat, and treatment outcomes are
      difficult to measure The majority of people who experience tinnitus are not
      troubled by it; however, the troubled minority are referred by an
      otorhinolaryngologist for specialist clinic help. The aim of this study was to
      investigate how the impact of tinnitus changes following attendance at a tinnitus
      clinic and to find out how acceptable the questionnaires used were for measuring
      recovery. Fifty-seven tinnitus sufferers completed three questionnaires covering
      the characteristics of tinnitus, and its effect on daily life, quality of life,
      and quality of family life, before and after treatment at the Nottingham Tinnitus
      Clinic. Questionnaires were answered at patients' homes while they were on the
      waiting list to attend the clinic, and again I year after their first attendance.
      Measures of functional and social handicap were significantly reduced following
      attendance at the clinic (mean change in functional handicap = 13%, p<0.01, and
      mean change in social handicap = 8%, p<0.01). Quality of life was significantly
      better after treatment at the clinic (mean visual analog scale difference = 6.5%,
      p = 0.01). We conclude that attendance at the Nottingham Tinnitus Clinic had a
      positive effect on the impact of tinnitus on patients and their families, and
      that the questionnaires gave an accurate measure of patient distress.

PMID- 15515641
TI  - Auditory brainstem response threshold estimation: subjective threshold estimation
      by experienced clinicians in a computer simulation of the clinical test.
AB  - Little research has been undertaken into the extent to which auditory brainstem
      response (ABR) threshold estimation varies between experienced professionals. In
      this paper, results are presented for 16 professionals who estimated ABR
      threshold for 12 sets of data in a computer simulation of the clinical test. The
      design differs from previous research in this area in that subjects had control
      over the creation of the set of traces from which they would estimate threshold,
      much as they would in the clinical situation. No agreement for threshold was
      found for any of the 12 sets of test data across the 16 subjects, and for nine of
      the sets, the difference between highest and lowest estimated threshold was 40 dB
      or greater. The maximum difference between highest and lowest estimated threshold
      was 60 dB. It is argued that the variability is not accounted for by experimental
      design. The implications for clinical practice are discussed.

PMID- 15515642
TI  - Naming difficulties in children with dyslexia: application of the tip-of-the
      tongue paradigm.
AB  - The present study used the tip-of-the-tongue (TOT) experimental paradigm in a
      picture naming task to explore the source of the naming deficits of children with
      dyslexia. Compared with a control group of typically developing readers, the
      children with dyslexia showed fewer correct responses and spontaneous recalls,
      more don't know (DK) and TOT responses, and less accurate feeling of knowing
      (FOK) judgments. When they failed to retrieve a target word, the children with
      dyslexia did not differ from the control group in the partial semantic
      information they provided, but they gave less valid and more invalid partial
      phonological information. The children with dyslexia also benefited less from
      phonological cues. The phonologically related responses of the children with
      dyslexia elicited during the administration of the TOT procedure were related to
      their performance on a phonological awareness test. These findings suggest that
      the naming problems of children with dyslexia arise because of their difficulty
      in accessing the phonological word forms after the corresponding abstract lexical
      representation has been successfully accessed. The results are discussed in
      relation to the claim that two-stage models of naming can be profitably used in
      the early identification and treatment of reading disabilities.

PMID- 15515643
TI  - Clock drawing in developmental dyslexia.
AB  - Although developmental dyslexia is often defined as a language-based reading
      impairment not attributable to low intelligence or educational or socioeconomic
      limitations, the behavioral manifestations of dyslexia are not restricted to the
      realm of language. Functional brain imaging studies have shed light on
      physiological differences associated with poor reading both inside and outside
      the classical language areas of the brain. Concurrently, clinically useful tests
      that elicit these nonlinguistic deficits are few. Specifically, the integrity of
      the dorsal visual pathway, which predominantly projects to the parietal cortex,
      remains underinvestigated, lacking easily administered tests. Here we present the
      Clock Drawing Test (CDT), used to test the visuoconstructive ability of children
      with and without dyslexia and garden-variety poor readers. Compared to typically
      reading children, many children with dyslexia and some garden-variety poor
      readers showed significant left neglect, as measured by the distribution of
      figures drawn on the left clock face. In the poor readers with dyslexia, we
      observed spatial construction deficits like those of patients with acquired right
      hemisphere lesions. The results suggest that in some children with dyslexia,
      right-hemisphere dysfunction may compound the phonological processing deficits
      attributed to the left hemisphere. The CDT provides an easy opportunity to assess
      skills known to be associated with right-hemisphere parietal function. This test
      can be easily administered to children for both clinical and research purposes.

PMID- 15515644
TI  - Memory performance of children with dyslexia: a comparative analysis of
      theoretical perspectives.
AB  - This study examined the memory performance of children with reading disabilities
      (RD) using methodology representative of three theoretical perspectives on RD
      subtypes: the phonological deficit, dual route, and phonological-core variable
      difference models. Analyses compared the serial memory, verbal learning, and
      abstract visual-spatial memory performance of 45 children with RD to that of
      chronological-age (CA)- and reading-level (RL)-matched controls, using subtype
      identification methods from each of the theoretical models to classify children
      with RD. Phonological deficit and dual route comparisons indicated that children
      with RD, regardless of subtype, performed more poorly than CA- and better than RL
      matched participants on all memory tasks. Phonological-core variable-difference
      methodology yielded three RD subtypes, two of which exhibited distinctive memory
      deficits relative to both CA and RL control groups. The phonological-core
      variable-difference model accounted for more variance in memory performance than
      either of the other two models.

PMID- 15515645
TI  - Students with learning disabilities in higher education: academic strategies
      profile.
AB  - This study compared 191 college students with learning disabilities (LD) and 190
      students without LD in four main areas: academic difficulties, learning
      strategies, functioning during examinations, and students' perception of factors
      that help or impede their academic success. Analysis of the personal data of
      students with and without LD revealed no significant differences between groups
      on grade point average, number of courses taken, and family status, but students
      with LD reported having more difficulties in humanities, social sciences, and
      foreign language than students without LD. Regarding academic strategies,
      students with LD devised unusual strategies and preferred additional oral
      explanations or visual explanations, whereas nondisabled students preferred more
      written examples. These differences indicated that students without LD used more
      written techniques than did students with LD. During examinations, the students
      with LD had difficulty concentrating and were concerned about lack of time. They
      experienced stress, were nervous, and felt more frustrated, helpless, or
      uncertain during examinations than students without LD. The implications for
      college students with LD are discussed.

PMID- 15515646
TI  - Evidence for unexpected weaknesses in learning in children with attention
      deficit/hyperactivity disorder without reading disabilities.
AB  - This study examined the mechanisms underlying verbal learning in children with
      and without attention-deficit/hyperactivity disorder (ADHD), none of whom had
      reading disabilities. Children with ADHD were compared to typically developing
      children on both process and product scores from the California Verbal Learning
      Test for Children. The findings indicated that children with ADHD initially
      learned the same number of words as controls but showed weaknesses recalling the
      words after delays, suggesting that children with ADHD are less efficient
      learners. Regardless of ADHD status, boys and girls performed differently. Boys
      used semantic clustering less frequently and recalled fewer words from the middle
      region of the list than girls; girls also outperformed boys in terms of overall
      performance, despite lower verbal IQ scores. These findings show that children
      with ADHD can exhibit unexpected weaknesses in learning even without a formal
      learning disability. Gender differences in verbal learning are also illustrated.

PMID- 15515647
TI  - The differential impact of academic self-regulatory methods on academic
      achievement among university students with and without learning disabilities.
AB  - Although research on academic self-regulation has proliferated in recent years,
      no studies have investigated the question of whether the perceived usefulness and
      the use of standard self-regulated learning strategies and compensation
      strategies provide a differential prediction of academic achievement for
      university students with and without learning disabilities (LD). We developed and
      tested a model explaining interrelationships among self-regulatory variables and
      grade point average (GPA) using structural equation modeling and multiple group
      analysis for students with LD (n = 53) and without LD (n = 421). Data were
      gathered using a new instrument, the Learning Strategies and Study Skills survey.
      The results of this study indicate that students with LD differed significantly
      from students without LD in the relationships between their motivation for and
      use of standard self-regulated learning strategies and compensation strategies,
      which in turn provided a differential explanation of academic achievement for
      students with and without LD. These paths of influence and idiosyncrasies of
      academic self-regulation among students with LD were interpreted in terms of
      social cognitive theory, metacognitive theory, and research conducted in the LD
      field.

PMID- 15515648
TI  - Comparing the self-concept of students with and without learning disabilities.
AB  - This study compared self-concept in 50 middle school children with learning
      disabilities (LD) and 70 of their peers without LD. The students, primarily
      Hispanic, completed the Piers-Harris Children's Self-Concept Scale, and each
      obtained a score in six subdomains. Differences were found between the groups on
      the Intellectual and School Status and Behavior subscales, with students without
      LD scoring higher on both scales. There was no difference between groups on
      global self-concept. The limitations of this study are identified, and directions
      for future research are provided.

PMID- 15515649
TI  - Allograft tympanoplasty.
AB  - Tympano-ossicular allografts are human transplants of the tympanic membrane alone
      or with the ossicles included. The authors review its use in their department
      since the introduction of the technique 40 years ago by J. Marquet. The
      advantages of the technique (near normal anatomical and physiological
      reconstruction) are discussed, as well as its disadvantages (time consuming
      harvesting, risk of disease transmission). Some technical modifications for
      specific indications have been adapted in our department and are described in
      detail. The authors believe that the tympano-ossicular allograft is the material
      of choice in extensively diseased middle ears destroyed by chronic otitis media
      with or without cholesteatoma.

PMID- 15515650
TI  - Open cavities in cholesteatoma surgery: checklist for proper surgery and
      perioperative care.
AB  - Decisions in cholesteatoma surgery regarding open versus closed techniques are
      based on the extent of the cholesteatoma, the degree of pneumatization of the
      middle ear and mastoid and the integrity of the remaining mucosa following
      complete resection of all disease. Checklists regarding handling of the soft
      tissues, drilling of the temporal bone with complete exenteration of the
      tympanomastoid air cell tracts, lowering of the facial ridge, partial
      obliteration of the cavity and meatoplasty and postoperative care are presented.
      Adhering to these checklists should enable every otologic surgeon to perform a
      safe open cavity and to end up with a dry, mostly self-cleaning cavity.

PMID- 15515651
TI  - The role of the KTP laser in cholesteatoma surgery.
AB  - INTRODUCTION: The primary aim in cholesteatoma surgery is the removal of the
      disease. As a result, most residual disease is found in sites which are both
      adjacent to the ossicles and hidden from direct view. An ideal instrument should
      be able to remove disease without movement and should be able to remove disease
      from regions to which there is no direct access. The laser fullfills this
      criteria. MATERIALS AND METHODS: Ears which underwent canal wall-up cholesteatoma
      surgery without the laser were compared with ears which underwent surgery which
      included the KTP laser since 1991. RESULTS: A total of 514 procedures was
      analysed (313 without laser and 201 with laser). We obtained respectively 83
      (26.5%) and 21 (10.4%) residual disease (P < 0.0001). The procedures involving
      the KTP laser resulted in no cases of facial nerve injury and no cases of total
      sensorineural hearing loss. CONCLUSION: We can conclude that the appropriately
      use of the KTP laser during cholesteatoma surgery does improve significantly the
      complete removal of disease and presents no extra risk to the vital structures
      within the temporal bone.

PMID- 15515652
TI  - Facial nerve outcome in non-vestibular schwannoma tumour surgery.
AB  - PROBLEMS/OBJECTIVES: Tumour size, intra-operative electrophysiologic thresholds
      and postoperative facial nerve function have been demonstrated to be important
      predictors of ultimate facial nerve function after vestibular schwannoma surgery.
      In general little attention has been given to the prediction of outcome of facial
      nerve function in non-vestibular schwannoma tumour surgery of the
      cerebellopontine angle (CPA). METHODOLOGY: A prospective study was performed to
      assess the predictive value of patient, tumour histology and electrophysiologic
      factors in the estimation of ultimate facial nerve outcome after this form of
      surgery. RESULTS: Sixteen patients satisfied the requirements of the study. Poor
      long-term facial nerve outcome was associated with abnormal pre-operative facial
      nerve function, facial nerve schwannomas, premeatal meningiomas and
      electrophysiologic stimulation thresholds of greater than 0.1 mA. CONCLUSIONS: It
      is concluded that tumour histology and pre-operative facial nerve function are
      additional factors that must be considered in the prediction of facial nerve
      function after non-vestibular schwannoma surgery of the CPA.

PMID- 15515653
TI  - "Second ear" stapedotomy: is it safe?
AB  - This study reports the evaluation of "second ear" stapedotomiesy results in 23
      patients with otosclerosis. All pre- and post-operative audiological data, all
      relevant surgical information and patients' features were analyzed
      retrospectively. The air-bone gap showed a significant improvement in all
      patients. The bilateral audiometric thresholds improved in 20 (87.0%) patients;
      in 1 (4.3%) patient, unilateral improvement occurred with no changes in the other
      ear and in 2 (8.7%) patients improvement occurred in first operated ear and
      dropped in the second ear after the last procedure. During the follow-up, there
      were no incapacitating complications. Based on these findings, we can conclude
      Our study concluded that second ear stapedotomy is a safe procedure with good
      results.

PMID- 15515654
TI  - Long term audiological evaluation of beta-thalassemic patients.
AB  - OBJECTIVE: The objective of this study was to identify the incidence and to
      monitor the progression of hearing loss in children and young adults with beta
      thalassemia major. METHODS: One hundred and four (104) patients aged 6-35 years
      (mean 17,2 years) participated in the study. All patients were on a regular
      transfusion-chelation program maintaining a mean hemoglobin level of 9.5 gr/dl.
      Subjects were receiving desferrioxamine (DFO) chelation treatment with a mean
      daily dose of 50-60 mg/kg, 5-6 days a week during the first six years of the
      study, which was then reduced to 40-50 mg/kg for the following eight years.
      Patients were followed for 8-14 years. RESULTS: Overall, 21 out of 104 patients
      (20.2%) presented with high frequency sensorineural hearing loss (SNHL), either
      unilateral or bilateral. No ototoxic factor, other than DFO, was present in any
      of the patients. Patients with SNHL presented with relatively lower serum
      ferritin levels than those with normal hearing, however, no statistically
      significant difference was observed. Subjects with SNHL were submitted to DFO
      reduction or temporary withdrawal. Following intervention, 7 out of 21 affected
      patients recovered, 10 remained stable and 4 demonstrated aggravation.
      CONCLUSION: The findings are indicative of DFO's contributing role in the
      development of hearing impairment. Regular audiologic evaluation is imperative in
      all thalassemic patients so that early changes may be recognized and treatment
      may be judiciously adjusted in order to prevent or reverse hearing impairment.

PMID- 15515655
TI  - Vestibular diuresis in suspected Meniere patients.
AB  - OBJECTIVE: Diagnosis of Meniere's disease in patients without classical symptoms
      may present some difficulty. Detection of hydrops in patients with normal or near
      to normal hearing or presenting unpredictable balance problem with great
      variability of severity, periodicity and duration is the major concern in
      reaching the accurate diagnosis to start the therapy as early as possible.
      METHOD: To investigate the diagnostic role of vestibular diuresis,
      electronystagmographic (ENG) evaluation of 20 patients with "probable" or
      "possible" Meniere's disease before and after intravenous furosemid
      administration has been reviewed in a prospective and blinded study and the
      results have been compared with 20 age-matched control subjects. RESULT: Eleven
      of 20 patients with Meniere's disease (55%) and one of 20 subjects in the control
      group (5%) demonstrated canal paresis at initial ENG testing. Thirteen patients
      from Meniere group (65%) and 1 subject from control group (5%) demonstrated
      positive response to furosemid. Seven of 11 patients with canal paresis in the
      patient group (63.7%) and 6 of 9 patients with no canal paresis at initial
      testing demonstrated positive response (66%) to furosemid. No statistical
      difference between these 2 subgroups was found when compared as response to
      furosemid. It has been found that there is no clear correlation between the
      duration of the disease and the positive response to furosemid. CONCLUSION: It
      has been concluded that, although some limitation exists, the sensitivity of
      furosemid test for evaluation of vestibular function in Meniere's disease is
      promising as compared with controls.

PMID- 15515656
TI  - Intraoperative measurement of parathyroid hormone in minimally invasive surgery
      for parathyroid adenoma.
AB  - INTRODUCTION: In the past bilateral neck exploration was the gold standard for
      successful surgical management of primary hyperparathyroidism. More restricted
      procedures have been introduced recently thanks to imaging techniques and
      intraoperative parathyroid hormone assay confirming eradication of
      hyperfunctioning tissue. METHODS: Thirty patients operated for parathyroid
      adenoma were submitted to intraoperative PTH determination with Quick Pack
      immunochemiluminescent assay (Nichols lab.) prior to excision and 5, 10 and 20
      minutes after removal of the presumed hyperactive gland. Eleven patients were
      operated on by a minimally invasive procedure with videoassistance. RESULTS:
      Response to excision of the hyperfunctioning gland was evidenced by a significant
      decrease of PTH levels (50% of initial value) in 26 patients. Plasma PTH levels
      decreased by at least 80% of pre-excisional value after 20 minutes, 70% after 10
      minutes and by 50% after 5 minutes. In 2 cases, significant decrease of PTH was
      obtained after 45 and 60 minutes respectively. In 2 other cases, the adenoma
      could not be found and there was no decrease of PTH even after extensive
      exploration of the neck. In the 11 patients who underwent minimal invasive
      surgery, 2 were converted to open neck surgery: in one case the adenoma was not
      accessible in the upper part of the neck, in the other case the hyperfunctioning
      gland remained undiscovered. CONCLUSION: intraoperative measurement of PTH should
      be considered a reliable and reproducible method for evaluation of the secreting
      activity of a parathyroid gland. The Quick Pack method has the advantage of
      confirming that the hyperactive gland has really been eradicated and consequently
      of considerably reducing operating time and avoiding extensive exploration of the
      neck.

PMID- 15515657
TI  - Nasopalatine duct cyst (NPDc): one case report.
AB  - OBJECTIVES: NPDc arises from embryological tissue. It is classified among the
      epithelial non-odontogenic cysts according to the 1992 WHO histological typing of
      odontogenic tumors. The purpose of our report was to provide details about the
      pathophysiology, diagnosis and treatment of NPDc. CASE REPORT: A 25 year-old male
      was referred by his practitioner regarding to an intermittent palatal swelling
      for 6 months. Diagnosis of NPDc was suggested on the basis of computed tomography
      (CT-scan). Excision was performed under general anaesthesia. There was no post
      operative complication. Histological features confirmed an inflamed NPDc. Follow
      up was 22 months, without relapse. CONCLUSION: NPDc occurs in approximately 1% of
      the population and forms approximately 12% of all jaw cyst tumors. NPDc may occur
      at any age, but main cases are seen between 40 and 60 years old. It has a slight
      male predilection. Black and white people are equally involved. NPDc is normally
      asymptomatic, unless it is infected. The most common symptom is swelling, usually
      in the anterior part of palate's midline. Diagnosis is based on radiographic and
      histological results. Treatment of choice is enucleation.

PMID- 15515658
TI  - Carotid artery occlusion due to fulminant rhinocerebral mucormycosis.
AB  - Mucormycosis is a rare disorder with a potentially lethal course caused by an
      opportunistic fungus of the Phycomycetes family. Rhinocerebral mucormycosis (RCM)
      is an acute fulminant form of invasive fungal sinusitis occurring principally in
      individuals who are immunologically or metabolically compromised. This form
      originates from one of the paranasal sinuses and may spread to the orbit or the
      intracranial space either by direct extension or using the unique capability of
      spreading along vascular walls, leaving the bony structure intact. Carotid artery
      occlusion is a complication of RCM. Because of the rapidity with which this
      disease progresses, prompt and aggressive therapy is essential. The morbidity and
      mortality of this disease are directly related to the length of time before
      diagnosis and treatment. The diagnosis is difficult because invasive mucormycosis
      may be present with no mucosal changes and a normal sinus CT scan. It is a
      histological diagnosis. Treatment of RCM includes early diagnosis, correction of
      underlying conditions, early and radical surgical debridement, and lipid
      formulation of amphotericin B. Multiple surgeries are often necessary for
      adequate debridement. We report a case of carotid artery occlusion due to RCM and
      discuss the literature on its early signs and symptoms, pathophysiology, and
      treatment options.

PMID- 15515659
TI  - [Provisions for long-term at home ventilated patient: consensus recommendations
      of the Austrian Society for Lung Diseases and Tuberculosis].

PMID- 15515660
TI  - [Physiopathology and treatment of anemia--recent progress].

PMID- 15515661
TI  - [Physiopathology and treatment of chronic heart failure].

PMID- 15515662
TI  - [Physiopathology and etiological mechanism involving type 2 diabetes mellitus].

PMID- 15515663
TI  - [Molecular mechanism and clinical description of hematopoiesis].

PMID- 15515664
TI  - [Diffuse pan-bronchiolitis and newly discovered macrolide actions].

PMID- 15515665
TI  - [From autoimmune hepatitis to the development of immunotherapy of cancer].

PMID- 15515666
TI  - [ Progress in the diagnosis of acute cerebrovascular disorder].

PMID- 15515667
TI  - [Summary of the treatment during the acute stage and related problems found in
      the initial guideline for the treatment of strokes].

PMID- 15515668
TI  - [The current status and evaluation of the treatment of acute cerebral infarction
      founded on evidence-based medicine (EBM)].

PMID- 15515669
TI  - [Evidence-based medicine (EVM) for thrombolytic therapy during the ultra-acute
      stage of cerebrovascular diseases and its current status in Japan].

PMID- 15515670
TI  - [Prospect for the therapy of cerebrovascular disorders during the acute stage].

PMID- 15515671
TI  - [Correct use of antibacterial agents and its guideline. 1) The status of the use
      of antibacterials and the trends in drug-resistant organisms].

PMID- 15515672
TI  - [Proper use of antibiotics and related guidelines: uniqueness of the Japanese
      guidelines].

PMID- 15515673
TI  - [Proper use of antibiotics and related guidelines. The future formats--global or
      regional standard?].

PMID- 15515674
TI  - [Proper use of antibiotics and related guidelines. The future image for the
      guidelines--global or regional standard?].

PMID- 15515675
TI  - [Kidney diseases--from diagnosis to transplantation. 2) Early diagnosis].

PMID- 15515676
TI  - [Kidney diseases--from diagnosis to transplantation. 3) Treatment given intended
      to conserve the host kidney].

PMID- 15515677
TI  - [Kidney diseases--from diagnosis to transplantation. 4) Dialysis therapy].

PMID- 15515678
TI  - [Kidney diseases--from diagnosis to transplantation. 5) Kidney transplantation].

PMID- 15515679
TI  - [Medical education: a comparison between the United States and Japan].

PMID- 15515680
TI  - [Postgraduate medical education: studies of internal medicine at teaching
      hospitals].

PMID- 15515681
TI  - [Safe medical treatment. "re-evaluation" for "safer" practice and "presentation
      of problems"].

PMID- 15515682
TI  - [EBM: guidelines and the quality of medical care].

PMID- 15515683
TI  - [Determination of the quality of health care].

PMID- 15515684
TI  - [Diagnosis and treatment of thrombocytopenia].

PMID- 15515685
TI  - [Renal osteodystrophy].

PMID- 15515686
TI  - [Clinical application of home blood determination].

PMID- 15515687
TI  - [Central nervous system disorders associated with allergic diseases].

PMID- 15515688
TI  - [Clinical differentiation among community-acquired pneumonia, bacterial
      pneumonia, and atypical pneumonia].

PMID- 15515689
TI  - [Collagen diseases and autoantibodies--current topics].

PMID- 15515690
TI  - [Clinical description of Q fever--new recognition as a common disease].

PMID- 15515691
TI  - [Molecular targeting in the treatment of lung cancer--toward the development of
      individualized treatment].

PMID- 15515692
TI  - [Clinical description of neuropathies].

PMID- 15515694
TI  - [Progress in the treatment of hyperlipemia].

PMID- 15515693
TI  - [Physiopathology and clinical description of acute renal failure].

PMID- 15515695
TI  - [Progress in chemotherapy of rheumatoid arthritis].

PMID- 15515696
TI  - [Therapeutic strategy for viral hepatitis].

PMID- 15515697
TI  - [Molecular physiopathology and clinical description of iron deficiency and iron
      overload].

PMID- 15515698
TI  - [Latest development in the treatment of heat failure based on evidence].

PMID- 15515699
TI  - [Metabolic action of growth hormone (GH)--clinical description of GH deficiency
      in adults].

PMID- 15515700
TI  - [Emerging and re-emerging infections].

PMID- 15515701
TI  - [Cholelithiasis--life style and the latest therapeutic methods].

PMID- 15515702
TI  - [Communication device utilizing event-related potentials].
AB  - We had developed a communication system using a theory of P300 through a
      computer. 17 healthy subjects participated in all 3 experiments, while 4 ALS and
      1 OPCA patients took part in the first 2 experiments only. In the 1st experiment,
      4 short sentences of 'yes very much', 'yes' 'no' and 'can't answer' were shown on
      the display. The subjects were asked to select one of them as target. During the
      experiment 1, color of background was randomly changed for each sentence as the
      stimulation for the period of 300 msec and the interstimulus interval was 1,500
      msec. In the 2nd experiment, 46 letters of Japanese character and several symbols
      were shown on the display (5 columns x 10 rows). In the 3rd experiment, we used
      16 pictures together with X (4 columns x 5 rows). During recordings, the color of
      background was randomly changed for each row and then for each letter/picture of
      column containing target in experiment 2 as well as in experiment 3. The subjects
      were asked to start counting and when the target was stimulated, they were
      instructed to stop the counting process and repeat counting again until they
      encountered the stimulation of target again. This was repeated for the entire
      recordings. Computer defined a target by a biggest positive voltage between 300
      and 600 msec and/or by the most powerful spectrum in 2-5 Hz after Fast Fourier
      transform in an averaged P300 (averaging number = 5-7). We then calculated the
      percentage of correct target by comparing the result and actual target. Results
      indicate that this communication aids can be used conveniently in patients with
      severe motor disabilities.

PMID- 15515703
TI  - [Spinal cord infarction due to cholesterol emboli complicating intra-aortic
      balloon pumping (case report and review of the literature)].
AB  - A 62-year-old man with diabetes mellitus, hypertension, and hyperlipidemia was
      admitted to our hospital because of sudden onset of left chest pain. He was
      diagnosed with unstable angina with left heart failure and underwent intra-aortic
      balloon pumping (IABP) immediately. On the 3rd day after removal of the IABP (7th
      hospital day), he developed sudden paraplegia with pain. Spinal MRI on the 12th
      hospital day revealed a spinal swelling (Th11-L2). He was died of cardiac shock
      on the 19th hospital day. Autopsy examination of the spinal cord revealed a large
      infarct from the lower thoracic segment to the sacral segment. Microscopic
      examination of these areas disclosed occlusive emboli most frequently of the
      anterior spinal arteries including posterior spinal arteries. These emboli were
      found in two different forms, one consisting of new cholesterol emboli and the
      other of old atheromatous emboli. On autopsy, the aorta exhibited severe
      atherosclerosis with multiple ulcerative plaques, and there was infarction of the
      spleen. In our case, spinal cord infarction was caused by a massive amount of
      cholesterol crystals from the aorta related to IABP.

PMID- 15515704
TI  - [Inclusion body myositis after interferon-alpha treatment in a patient with HCV
      and HTLV-1 infection].
AB  - We report the first case of inclusion body myositis (IBM) which occurred after
      interferon-alpha treatment for chronic hepatitis C. A 63-year-old man contracted
      hepatitis C virus (HCV) and human T cell leukemia virus type 1 (HTLV-1) from a
      blood transfusion at age of 18. At age 57, he was treated with interferon-alpha
      (IFN alpha) for chronic hepatitis C. A month later, he developed muscle weakness
      in the proximal part of his lower extremities. IBM was diagnosed after a muscle
      biopsy at age 62. Steroid therapy improved his muscle power. One year later,
      worsening of his hepatic condition required re-administration of IFN alpha after
      gradual decrease and discontinuation of prednisolone. However, several days
      later, he rapidly became weaker and required a cane to walk. Elevated serum
      creatine kinase (2,199IU/L) and abnormal intensity in his MRI of thigh were
      demonstrated. The second muscle biopsy, performed after obtaining the informed
      consent from our patient, confirmed relapse of IBM. His symptoms improved again
      after discontinuation of IFN alpha and re-induction of prednisolone. Although a
      few cases each of IBM associated with HCV or HTLV-1 have been reported, the
      pathogenesis of virus-associated inflammatory myositis has not been clearly
      understood. Moreover, there has been no description on IBM associated with IFN
      alpha treatment, though several cases of polymyositis have been reported. Our
      case suggests that infection of HCV and HTLV-1 may be immunologically involved in
      the development of IBM and that IFN alpha can be directly related to onset and
      relapse of IBM.

PMID- 15515705
TI  - [Early detection of brain damages in status epilepticus using apparent diffusion
      coefficient mapping].
AB  - We report two patients of status epilepticus, in which detailed brain magnetic
      resonance image (MRI) studies were performed. In one patient apparent diffusion
      coefficient (ADC) increased in the right temporopareital regions in the acute
      phase. This patient finally has good clinical course without neurological
      deficits, and abnormal findings on MRI also disappeared. In another patient ADC
      increased in the similar regions in the acute phase, and an MRI demonstrated
      cortical laminar necrosis on T1-weighted scans in the same regions in the
      posticteric phase about 3 months later. The patient had a poorer prognosis with
      moderate dementia. It has been demonstrated that increased ADC reflects
      extracellular edema, while decreased ADC indicates cytotoxic edema. ADC mapping
      appears to be useful for predicting the reversibility of brain damages due to
      status epilepticus.

PMID- 15515706
TI  - [A case of steroid-responsive encephalopathy with positive 14-3-3 protein of the
      cerebrospinal fluid clinically resembling Creutzfelt-Jakob disease].
AB  - A 69-year old man developed subacutely progressive dementia, inactivity, and gait
      disturbance. On admission, he showed flutter-like oscillation of the bilateral
      eyes and myoclonus with upper extremities. Cerebrospinal fluid (CSF) analysis
      revealed elevation of protein (73.2mg/dl) and the positive 14-3-3 protein. An
      electroencephalogram (EEG) revealed diffuse slowing (2-3Hz, 80microV). Brain MRI
      showed high intensity lesions in the white matter and left thalamus on FLAIR and
      diffusion imaging. We first suspected Creutzfelt-Jakob disease (CJD), but his
      symptoms didn't progress and showed no PSD on EEG. Oral corticosteroid therapy
      (prednisolone 60mg/day) brought him remarkable recovery corresponding with
      improvement of CSF and EEG findings. Despite of etiology unknown, we made a
      diagnosis of steroid-responsive encephalopathy.

PMID- 15515707
TI  - [Cervical myelopathy in a patient with congenital cervico-cerebral vascular
      malformation].
AB  - We report a 50 year-old woman with cervical myelopathy. The patient, who had
      cutaneous angiomas in the right orbital area, became aware of left upper limb
      weakness when she woke up, followed by painful abnormal sensation in both axilla
      and arms. MRI revealed an intramedullar lesion mainly located in cervical cord at
      the level of C3-C4. Angiography showed that serpentine left vertebral artery
      entered the canalis vertebralis at C3 and fed the blood flow of bilateral middle
      cerebral arteries. In this case, the upper cervical spinal cord ischemia might be
      induced by hemodynamic insufficiency of the anterior spinal artery ascribed to
      congenital cervico-cerebral vascular malformation.

PMID- 15515708
TI  - [Acute brain infarction clearly demonstrated by using the three-dimensional
      stereotactic surface projections (3D-SSP) of 99mTc-HMPAO SPECT].
AB  - We report a 66-year-old ambidextrous man who suddenly developed aphasia seven
      days after coronary artery bypass grafting surgery. CT scan performed 30 minutes
      after onset failed to depict acute ischemic lesion. MR imaging could not be
      performed because of intrathoracic wires. An emergent angiogram demonstrated
      filling defect in the right precentral artery territory. Transaxial images of
      99mTc-HMPAO SPECT showed hypoperfusion areas in the right frontal and left
      temporo-parietal regions. Using the three-dimensional stereotactic surface
      projections (3D-SSP) of 99mTc-HMPAO SPECT, we could clearly detect a sharply
      demarcated ischemic area which was later confirmed to be an infracted lesion in
      the follow-up CT. 3D-SSP, thus, appears to be useful for identifying acute
      infarction in such cases that MRI is impermissible.

PMID- 15515709
TI  - [Details about the first medical examinations of patients with Guillain-Barre or
      Fisher syndromes].
AB  - Randomized controlled trials have shown beneficial responses to plasma exchange
      and intravenous immunoglobulin in Guillain-Barre syndrome (GBS), but details
      about the first medical examination of patients with GBS and Fisher syndrome (FS)
      have not been reported. We investigated the period from first consultations to
      treatment after the onset of patients with GBS and FS. A questionnaire was used
      to collect informations on 247 patients with GBS and 125 with FS, all of whom had
      been referred to our neuroimmunological laboratory informations between January
      2001 and October 2001 for serum anti-ganglioside antibody tests. A letter of
      inquiry was sent to the primary physicians; 150 (61%) patients with GBS and 72
      (58%) with FS responded validly. Patients with GBS generally consulted an
      internist [58%, neurologist (21%)] or orthopedist (17%), those with FS an
      internist [52%, neurologist (26%)] or ophthalmologist (25%). Consultation with a
      neurologist usually came after one with a physician. We conclude that physicians
      should be aware that patients may have GBS or FS, and that such recognition is
      useful for early diagnosis and treatment of these syndromes.

PMID- 15515711
TI  - [A case of heparin-induced thrombocytopenia that worsened preexisting cerebral
      infarction].
AB  - A 75-year-old man was admitted to our hospital with dysesthesia of the right lip,
      dysphagia and gait disturbance. He presented with right Wallenberg syndrome and
      brain MR image showed a fresh infarction in the right lateral medulla. Therapy
      with heparin and ozagrel sodium was started. For a time his symptom improved a
      little, but after 8 days he developed re-infarction, thrombocytopenia and DIC,
      while being treated with heparin for cerebral infarction. Heparin was
      discontinued, and these symptoms improved quickly. The clinical course and the
      positive anti-platelet factor 4-heparin complex antibody suggested that these
      symptoms were caused by heparin-induced thrombocytopenia (HIT). HIT should be
      included as a differential diagnosis for progression of ischemic stroke under
      heparin therapy.

PMID- 15515710
TI  - [Intravenous immunoglobulin therapy for Guillain-Barre syndrome in Japan: changes
      in treatment after its inclusion in health insurance coverage].
AB  - In December 2000, health insurance in Japan was instituted for the use of
      intravenous immunoglobulin (IVIg) therapy for the acute phase of Guillain-Barre
      syndrome (GBS) that required aid to walk or worse. A nation-wide questionnaire
      survey was made to investigate the changes in treatment. In September 2002, a
      letter of inquiry was sent to experienced physicians in 620 teaching hospitals
      associated with the Societas Neurologica Japonica and 417 associated with the
      Societas Paediatrica Japonica. Totally, 356 neurologists (57%) and 223
      pediatricians (53%) responded. After the introduction of IVIg health insurance
      coverage, more than 90% thought that GBS patients should be hospitalized and
      given treatment. The frequency of hospitals with an intensive care unit, however,
      was 70%. Before IVIg therapy's inclusion in health insurance coverage, many
      neurologists selected plasmapheresis (88%) rather than IVIg (4%) therapy, whereas
      pediatricians preferred IVIg (49%) to plasmapheresis (12%). After its inclusion,
      75% of neurologists selected IVIg rather than plasmapheresis (21%), whereas
      pediatricians selected IVIg (86%) over plasmapheresis (5%). In March 2003, new
      payment system based on Diagnosis Procedure Combination was introduced into 82
      large hospitals, and leads to difficulties to select IVIg in the hospitals. The
      payment system should be revised.

PMID- 15515712
TI  - [Cortical reflex myoclonus in adult onset Huntington's disease].
AB  - We report a case of cortical reflex myoclonus in adult onset Huntington's disease
      (HD). The patient is a 51-year-old woman. Chorea and myoclonus were observed on
      her face and extremities. Neurophysiological tests showed C reflex and abnormal
      waves preceding myoclonus by jerk-locked back averaging method but no giant
      somatosensory evoked potential. Gene analysis revealed the prolongation of CAG
      repeats (13/44) in IT15 gene. Oral administration of clonazepam was transiently
      effective for myoclonus. We should inscribe that the cortical reflex myoclonus
      may exceptionally manifest in HD.

PMID- 15515713
TI  - [A case of acute autonomic, sensory and motor neuropathy (AASMN)--less favorable
      response of the autonomic dysfunctions to IVIg treatment].
AB  - We report a rare case of acute autonomic, sensory and motor neuropathy (AASMN).
      The patient, a 26-year-old woman, developed fever and common cold around January
      20, 2001 and was admitted because of abdominal pain due to ileus on January 30.
      After admission, the patient complained of muscle weakness and numbness in the
      extremities, difficulty in seeing with the right eye, and dysuria.
      Neurologically, marked orthostatic hypotension, right tonic pupil, distal
      dominant moderate muscle weakness in extremities, areflexia in both lower limbs,
      glove and stocking type of paresthesia, and neurogenic atonic bladder were noted.
      Sensation to pin prick, light touch, temperature, and vibration were markedly
      impaired in upper limbs and below the level of the 5th thoracic cord.
      Cerebrospinal fluid examination revealed albumino-cytologic dissociation.
      Peripheral nerve conduction study revealed lower limb dominant axonal type
      impairment of sensory conduction and slight impairment of motor conduction
      velocity. Clinical autonomic testings revealed dysfunction of both sympathetic
      and parasympathetic systems. As having AASMN, she was given the intravenous high
      dose immunoglobulin (IVIg) therapy twice. After IVIg, the sensory and motor
      symptoms improved remarkably, but pandysautonomia did not. To our knowledge, this
      is the first report of AASMN treated by IVIg, and the notable clinical feature in
      this case was the favorable motor and sensory recovery to IVIg, as opposed to
      poor autonomic outcome.

PMID- 15515714
TI  - [Clinical investigation of squamous cell carcinoma of the posterior oropharyngeal
      wall].
AB  - Clinical features of 33 patients with squamous cell carcinoma of the posterior
      oropharyngeal wall treated at the Department of Otolaryngology, Head and Neck
      Surgery, Kurume University Hospital from 1973 to 2003 were analysed. Of these, 23
      (21 men and 2 women, mean age: 66 years) underwent radical treatment, and 10 (8
      men and 2 women, mean age: 78 years) did not. In those treated radically, 2 were
      stage I, 5 stage II, 6 stage III, and 10 stage IV. The primary disease was
      surgically treated in 16, and reconstruction added in 5, using the free jejunum
      in 4 and a forearm flap. Radical radiotherapy was done in 7. Five-year local
      control in the 23 was 35.3%. Disease-specific 5-year survival was 32.0%. Seven
      died of primary oropharyngeal cancer. After treatment, 78.3% were able to eat
      orally. In conclusion, squamous cell carcinoma of the posterior oropharyngeal
      wall is relatively rare and has a poorer prognosis than other types of
      oropharyngeal cancer.

PMID- 15515715
TI  - [Hearing outcome of canal wall reconstruction tympanoplasties for the treatment
      of cholesteatoma].
AB  - While the hearing outcome of patients undergoing a tympanoplasty with canal
      reconstruction is generally thought to be inferior to that of patients undergoing
      a canal-up tympanoplasty, a direct comparison of these two procedures, performed
      by the same operator, has not been reported. Consequently, we compared the
      hearing outcomes of these two techniques and discussed the postoperative
      complications that could accompany the procedures. Hearing was evaluated in 52
      ears with middle ear cholesteatoma. Using the postsurgical hearing result
      assessment criteria published by the Japanese Society of Otology in 2000, hearing
      was then evaluated again at least 6 months after surgery. When the data was
      analyzed according to the type of operation, the success rates (as determined
      using the above assessment criteria) were 78.6% for type I, 88.5% for modified
      type III, and 50.0% for modified type IV. The success rate for the modified type
      III operations was superior to that of the modified type IV operations, and the
      incidence of a postoperative air-bone gap in the type IV tympanoplasties was
      significantly larger than that in other groups. Procedures involving external
      auditory canal surgery can be particularly problematic for the treatment of
      cholesteatoma. In this series, the same author (KH) performed all the canal-up
      tympanoplasty procedures that took place during 1990-1996, and all other
      tympanoplasties, mainly canal reconstruction procedures, that took place during
      1998-2001. The success rate was 68.4% (13/19) for the canal-up tympanoplasties,
      100% (8/8) for the atticotomies and 76% (19/25) for the canal wall
      reconstructions. The postoperative success rate in the atticotomy group was
      significantly higher than the rates of the other groups. Among the canal
      reconstructive tympanoplasty procedures, a second exploratory surgery was
      performed in 15/24 cases, and residual cholesteatoma was observed in 3 cases. The
      major postoperative complications were epitympanic pocket formation (12/24) and
      taste disturbances, caused by chordal damage (2/24). These findings indicate that
      tympanoplasties with canal reconstruction improve the hearing outcome, compared
      with the outcome of canal-up tympanoplasties. However, epitympanic retraction
      pocket formation, resulting in recurrent cholesteatoma, is a possible
      complication of both surgical procedures, and new approaches or techniques should
      be sought to minimize such postoperative changes.

PMID- 15515716
TI  - [Factors influencing long-term progress in patients with vestibular neuritis].
AB  - We previously reported that platform stabilometry was effective in evaluating the
      condition of patients with vestibular neuritis. In the present study, we
      increased the patient population (n = 31) and followed them up for long-term
      (253.5 +/- 36.5 days after admission) to determine factors influencing prognosis.
      We examined the stability of patients with vestibular neuritis using platform
      stabilometry at 5 time points: P1, (5.3 +/- 0.7 days after admission); P2, (22.2
      +/- 1.2 days); P3, (73.2 +/- 2.5 days); P4, (159.2 +/- 9.2 days); and P5, (258.3
      +/- 23.5 days). For some elements--the total length of locus and the area of
      surroundings with open or closed eyes--the total length of locus with open eyes
      decreased significantly (P<0.05) following disease amelioration. Important
      factors for improving elements of platform stabilometry in patients with
      vestibular neuritis were age, presence of upper respiratory infection, and the
      duration of nystagmus.

PMID- 15515717
TI  - [3D-CT highly useful in diagnosing foreign bodies in the paraesophageal orifice].
AB  - Multislice computed tomography (CT) enables rapid, easy construction of 3
      dimensional CT images (3D-CT), aiding diagnostic imaging. 3D-CT is reported to be
      highly useful in diagnosing temporal bone disorders, in otorhinolaryngology,
      especially abnormal shape and the ossicular chain of the auditory ossicles and
      facial bone fractures. Given the complexity of laryngeal anatomy, 3D-CT is useful
      in diagnosing the extent of infiltration of laryngeal cancer and in examining
      vocal cord movement, which is difficult to evaluate by conventional CT, magnestic
      resonance imaging (MRI), and fiberscopy. Among patients seen for a suspected
      foreign body between June 2002 and May 2003, we chose 3 in whom laryngoscopy at
      the first examination could not detect a foreign body but in whom symptoms and
      findings suggested such presence in the paraesophageal orifice. In all 3 cases,
      3D-CT imaging showed the size, length, location, and direction of the foreign
      body, providing information useful for the surgical approach.

PMID- 15515718
TI  - [The economic and social costs of dementia].

PMID- 15515719
TI  - [Pathogenesis and treatment of cancer anorexia-cachexia, with special emphasis on
      aged patients].
AB  - Cachexia is among the most debilitating and life-threatening aspects of cancer
      and is more common in children and elderly patients. Associated with anorexia,
      fat and muscle tissue wasting, psychological distress, and a lower quality of
      life, cachexia arises from a complex interaction between the cancer and the host.
      This process results from a failure of the adaptive feeding response seen in
      simple starvation and includes cytokine production, release of lipid-mobilizing
      and proteolysis-inducing factors, and alterations in intermediary metabolism.
      Cytokines play a pivotal role in long-term inhibition of feeding by mimicking the
      hypothalamic effect of excessive negative feedback signaling from leptin, a
      hormone secreted by adipose tissue, which is an integral component of the
      homeostatic loop of body weight regulation. This could be caused by persistent
      inhibition of the feeding-stimulatory circuitry including neuropeptide Y.
      Cachexia should be suspected in patients with cancer if an involuntary weight
      loss of greater than five percent of premorbid weight occurs within a 3-6-month
      period. The two major options for pharmacological therapy have been either
      progestational agents or corticosteroids. However, knowledge of the mechanisms of
      cancer anorexia-cachexia syndrome has led to, and continues to lead to, effective
      therapeutic interventions for several aspects of the syndrome. These include
      antiserotonergic drugs, gastroprokinetic agents, branched-chain amino acids,
      eicosapentanoic acid, cannabinoids, melatonin, and thalidomide all of which act
      on the feeding-regulatory circuitry to increase appetite and inhibit tumor
      derived catabolic factors to antagonize tissue wasting and/or host cytokine
      release. Because weight loss shortens the survival time of cancer patients and
      decreases performance status, effective therapy would extend patient survival and
      improve quality of life.

PMID- 15515720
TI  - [Ghrelin and somatopause].

PMID- 15515721
TI  - [Aging lung in health and disease].

PMID- 15515722
TI  - [Past, present and future of geriatrics in Japan].

PMID- 15515723
TI  - [Treatment for peptic ulcer disease in the elderly patients--from new guideline
      for treatment of gastric ulcer based on EBM].

PMID- 15515725
TI  - [Aging of the brain and silent cerebrovascular diseases].

PMID- 15515724
TI  - [Treatment of hypertension in the elderly].

PMID- 15515726
TI  - [Prevention and measures against ischemic heart disease in the elderly].

PMID- 15515727
TI  - [Endocrinological adaptation to the aging-related events].

PMID- 15515728
TI  - [Presbycusis].

PMID- 15515729
TI  - [Rehabilitation of the elderly].

PMID- 15515730
TI  - [Management of hyperlipidemia in the elderly].

PMID- 15515731
TI  - [Antiarrhythmic therapy in the elderly].

PMID- 15515732
TI  - [Countermeasure against prostate cancer with advanced age].

PMID- 15515733
TI  - [Clinical features and problems of pulmonary tuberculosis in elderly patients].

PMID- 15515734
TI  - [A neuroradiological study on the influence of cerebral atrophy and white matter
      lesion on cognitive function in the elderly].
AB  - We investigated the influence of brain atrophy and white matter lesions on
      cognitive function in elderly people. We selected 33 subjects (mean age, 79.2 +/-
      5.1yrs) with a MMSE score from 14 to 30 who had no previous history of stroke
      from the outpatients in the Memory Clinic of our hospital. These subjects were
      divided into four groups on the basis of their MMSE score as follows: 14-20;
      moderate dementia (Moderate-D, n = 9), 21-23; mild dementia (Mild-D, n = 9), 24
      27; mild cognitive impairment (MCI, n = 10), 28-30; normal (Normal, n = 5). Among
      these four groups, we compared the frequency of the associated risk factors for
      cerebral infarction (hypertension, diabetes mellitus, hyperlipidemia, heart
      disease), and the severity of brain atrophy and cerebral white matter lesion
      which were visually evaluated by MRI technique. Brain atrophy and white matter
      lesions were assessed by reviewing the cerebral cortex and hippocampus, and deep
      white matter lesion (DWML) and periventricular hyperintensity (PVH),
      respectively. Brain atrophy was divided into three grades (mild, moderate,
      severe) and white matter lesions were classified into four grades (0-3) using
      Fazekas's criteria. We performed statistical analysis to detect t parameters
      which correlate with and influence MMSE scores from among the MRI findings. The
      cases with dementia were all diagnosed as Alzheimer's disease. There were no
      significant differences among the four groups in mean age, the incidence of
      individual associated risk factors, the severity of cortical atrophy, or the
      grade of DWML (< or = 2) and PVH (< or = 2). However, the frequency of
      hippocampal atrophic change greater than a moderate grade increased in parallel
      with the exacerbation of reduced cognitive function (Normal; 20%, MCI: 40%, Mild
      D; 56%, Moderate-D 89%), and approximately 76% with such a change were AD cases.
      Statistical analysis showed a significant negative correlation between the grade
      of hippocampal atrophy and MMSE score (r = -0.518, p < 0.005) and a great
      influence of hippocampal atrophy on that score (step-wise regression analysis: r
      = 0.518, p < 0.005). From the above results, it was suggested that more than
      moderate atrophic change in the hippocampus might possibly be related with
      cognitive impairment and that both DWML and PVH less than the second grade had
      little influence on the decline of brain function.

PMID- 15515735
TI  - [Nursing home directors' attitude toward medical decision-making and medical care
      for elderly people with dementia].
AB  - Medical decision-making involving elderly people with dementia often troubles
      care providers in Japan. Meanwhile, little attention has been paid to the routine
      medical care of nondementia illnesses in such patients. To understand the current
      situation surrounding the issue, we conducted a postal survey with nursing home
      directors across the nation. A self-administered questionnaire was sent to 1,117
      randomly selected nursing homes, one third of all such facilities in Japan, and
      502 (44.9%) responded. Of the respondents, 291 (58.0%) said more than a half of
      their residents have difficulties in daily life because of dementia. Less than
      20% of the facilities said that they routinely confirm residents' preferences in
      writing when they are admitted concerning each of the following items; terminal
      care, medical information disclosure, leaving a will, funerals and application
      for the guardian system. 206 (41.0%) facilities have difficulties in finding a
      hospital for the elderly with dementia when necessary. The Mann-Whitney U test
      showed no significant relation between facilities' characteristics and their
      difficulties in finding a hospital that would admit demented patients. At
      present, a number of nursing homes confirm their residents' preferences only some
      time after they are admitted. However, the way of confirming seems inappropriate
      under the circumstances in which more than a majority of residents have
      difficulties in daily life due to dementia. Though more than a half of nursing
      homes have difficulties in finding a hospital that would admit dementia patients,
      no significant relation was found between the difficulties and the facility
      hospital relation. The problem seems to lie in the acceptance mechanism of
      hospitals.

PMID- 15515736
TI  - [Acceptance of memory impairment and satisfaction with life in patients with mild
      to moderate Alzheimer's disease].
AB  - In this study, we focused on acceptance of memory impairment and satisfaction
      with life in patients with mild to moderate Alzheimer's disease (AD). We
      interviewed 71 consecutive patients with AD and asked (1) whether they had memory
      loss, (2) whether they found trouble in life, and (3) how their daily life was.
      We categorized the patients into three groups based on awareness of memory loss
      and reference to the cause of memory loss. Cognitive functions were lower in
      patients who were not aware of memory loss. The rate of satisfaction with life
      was the highest in patients who were not aware of memory loss, and was the lowest
      in patients who complained of memory loss with reference to the cause of memory
      loss, indicating that patients could hardly accept their lives when memory
      impairment was a serious issue. However, in these patients, depression scores
      were not high, suggesting that they may somehow adapt themselves to their current
      status by defining the reason for memory loss. In patients who complained of
      memory impairment but did not refer to the cause of memory loss, there was a
      variation in awareness of memory loss and satisfaction with life. The present
      study indicated that we have to provide individual care and support for AD
      patients considering their level of acceptance of memory impairment.

PMID- 15515737
TI  - [Relationships among urine pH, serum uric acid and pyuria in hospitalized elderly
      patients].
AB  - To identify risk factors of urinary tract infection (UTI) in geriatric patients,
      the levels of serum uric acid, serum creatinine, and urine pH were compared
      between pyuria-positive and -negative patients in a geriatric ward. The level of
      serum uric acid was higher with lower urine pH level in the pyuria-negative
      patients than in positive patients. The level of serum creatinine was relatively
      higher in the pyuria-negative patients than in the positive patients. Even after
      matching for serum creatinine, serum uric acid was significantly higher in the
      pyuria-negative male patients. The results in the present study proposed an
      interesting hypothesis about backgrounds for UTI in geriatric patients. The
      relationships among serum uric acid, serum creatinine, urine pH, and pyuria
      should be examined further in a larger population and in experimental studies.

PMID- 15515738
TI  - [A case of foxhole-shaped left ventricular abnormality induced by complete
      atrioventricular block with delayed recovery of wall motion].
AB  - An 86-year-old woman suffered sudden onset chest discomfort and dyspnea during
      sleep in the early morning of August 1, 2003. On admission, electrocardiography
      demonstrated complete atrioventricular block. Echocardiography showed severe
      hypokinesis in the left ventricular apex and hyperkinesis at the base. Serum
      cardiac deviant enzymes were slightly elevated. Based on these findings, acute
      myocardial infarction accompanied by complete atrioventricular block was
      suspected. Emergency coronary angiography performed under temporary pacing showed
      no significant stenosis in the coronary arteries. However, ventriculography
      demonstrated the presence of a foxhole-shaped left ventricular abnormality. A VDD
      type permanent pacemaker was implanted 5 days after the onset of the symptoms
      because the atrioventricular block had not improved. Following the implantation,
      pleural effusion and a temporary elevation of the body temperature occurred. The
      myocardial scintigraphy using 123I-metaiodobenzylguanidine (123I-MIBG) in the
      acute phase demonstrated extensive cardiac sympathetic nerve damage in the left
      ventricular apex. This condition was managed by medication including diuretics,
      angiotensin II receptor blocker and beta-blocker. Three months later,
      echocardiography and 123I-MIBG myocardial scintigraphy showed slight recovery of
      wall motion and sympathetic activity. However, mild pleural effusion persisted. A
      complete atrioventricular block was also present at this stage. In view of these
      findings, this case suggested that the foxhole-shaped left ventricular
      abnormality induced complete atrioventricular block with delayed recovery of wall
      motion.

PMID- 15515739
TI  - [Severe chlamydia pneumoniae pneumonia requiring mechanical ventilation and
      steroid therapy in an elderly patient].
AB  - A 75-year-old man first developed dyspnea and low-grade fever in late March. A
      chest X-ray film showed infiltration in the right lower lung field and blood gas
      analysis revealed severe hypoxemia. Accordingly, he was diagnosed as having
      pneumonia and was admitted to our hospital on March 11, 2003. Mechanical
      ventilation for progressive respiratory failure was started immediately after
      admission, and he was treated with antibiotics. Chlamydia pneumoniae pneumonia
      was diagnosed due to an increase of the Chlamydia pneumoniae antibody titer. He
      had prolonged respiratory failure despite antibiotic therapy. Therefore, steroid
      therapy was started on day 15 for respiratory failure. At 21 days after
      admission, the infiltration was found to be decreased on chest X-ray films and
      improvement of hypoxemia allowed extubation. In conclusion, when severe community
      acquired pneumonia occurs in elderly patients, we should remember the possibility
      of atypical pneumonia such as that due to Chlamydia pneumoniae infection.

PMID- 15515740
TI  - [The present condition and the future challenges on dental health policy].

PMID- 15515741
TI  - [A statistical survey of the fabrication of single restorations (in 2002)].
AB  - A statistical survey based on laboratory records was carried out to determine the
      state of fabrication of restorations at the dental hospital of Tokyo Medical and
      Dental University during the six month period from April 1 to September 30, 2002.
      A comparison was also done with a previous survey that had been carried out in
      1986 and 1997 to detect the possible change and alternations in the near future.
      From the findings of this survey, the following conclusions can be drawn. 1. A
      total of 7,864 restorations were fabricated during the six months in 2002, and of
      these, 6,740 restorations (85.7%) were covered by health insurance, and 1,124
      (14.3%) were not. 2. Compared with the previous data in 1986 and 1997, decreased
      numbers of inlays and cast post & cores were the distinctive features that
      affected the decrease of total numbers. 3. The rate of restorations that were not
      covered by health insurance slightly increased to 14.3%, compared with 12.3% in
      1997.

PMID- 15515742
TI  - [Statistical analysis of the fabrication of fixed and removable partial dentures
      (in 2002)].
AB  - A statistical survey based on laboratory records was performed on the number of
      fixed partial dentures and removable partial dentures fabricated at the dental
      hospital of Tokyo Medical and Dental University from April 1 to September 30,
      2002. A comparison was also performed with a previous survey that had been
      carried out in 1997 to detect any change and possible alternations in the near
      future. From the findings of this statistical survey, the conclusions were as
      follows: 1. A total of 2,656 fixed and removable partial dentures were fabricated
      during the six-month period in 2002. 2. The 3-unit fixed partial denture was most
      common (64.0%), and the number of fixed partial dentures decreased as the number
      of units increased. 3. For a single missing tooth, a fixed partial denture was
      more popular (80.8%) than a removable partial denture. 4. For two missing teeth,
      there was little difference between the number of fixed and removable partial
      dentures. In the anterior region, fixed partial denture was more common, while in
      contrast, in the posterior region, removable partial denture was more common.

PMID- 15515743
TI  - Significance of 123I-MIBG scintigraphy as a pathophysiological indicator in the
      assessment of Parkinson's disease and related disorders: it can be a specific
      marker for Lewy body disease.
AB  - Recently, reliable and clear evidence for the usefulness of 123I-MIBG
      scintigraphy in the diagnosis of Parkinson's disease (PD) has been accumulated
      and it has become increasingly popular as one of the most accurate means of
      diagnosing the disease. PD, one of the most common neurodegenerative disorders,
      is characterized by resting tremor, rigidity, bradykinesia or akinesia, and
      postural instability. The disease is characterized pathologically by distinctive
      neuronal inclusions called Lewy bodies in many surviving cells of dopaminergic
      neurons of the substantia nigra pars compacta and other specific brain regions.
      Furthermore Lewy body type degeneration in the cardiac plexus has been observed
      in PD. In PD, cardiac MIBG uptake is reduced markedly even in the early disease
      stages; therefore, MIBG imaging can be used as an indicator of the presence of PD
      rather than disease severity. Other parkinsonian syndromes such as multiple
      system atrophy, progressive supranuclear palsy, and corticobasal degeneration
      demonstrate normal cardiac MIBG uptake or only mild reduction of MIBG uptake,
      indicating that MIBG imaging is a powerful method to differentiate PD from other
      parkinsonian syndromes. Dementia with Lewy bodies (DLB) also shows severe
      reduction of MIBG uptake, whereas Alzheimer's disease (AD) demonstrates normal
      MIBG uptake, permitting differentiation of DLB from AD using MIBG scintigraphy.
      In pure autonomic failure, which shares similar pathological findings with PD and
      is thought to be associated with diffuse loss of sympathetic terminal
      innervation, cardiac MIBG uptake also decreases markedly. Considering all the
      data together, marked reduction of cardiac MIBG uptake seems to be a specific
      marker of Lewy body disease and thus extremely useful in the differentiation from
      other diseases with similar symptoms without Lewy bodies.

PMID- 15515744
TI  - Evaluation of myocardial viability following acute myocardial infarction using
      201Tl SPECT after thallium-glucose-insulin infusion--comparison with 18F-FDG
      positron emission tomography.
AB  - OBJECTIVE AND METHODS: The aim of this study was to evaluate myocardial viability
      in patients after acute myocardial infarction (AMI). We compared 201Tl SPECT
      after 201Tl with GIK (10% glucose 250 ml, insulin 5 U and KCl 10 mEq) infusion
      (GIK-201Tl) with resting 201Tl and 99mTc-pyrophosphate (PYP) dual SPECT, positron
      emission computed tomography (PET) using 18F-fluorodeoxyglucose (18F-FDG) in 21
      patients with their first AMI, who all underwent successful reperfusion. GIK
      201Tl SPECT, 201Tl and 99mTc-PYP dual SPECT were done within 10 days after
      admission and 18F-FDG-PET was performed at 3 weeks. GIK-201Tl SPECT was obtained
      after 30 min of GIK-201Tl infusion. 18F-FDG (370 MBq) was injected intravenously
      after oral glucose (1 g/ kg) loading, and then PET was obtained. PET and SPECT
      images were divided into 20 segments. Regional tracer uptake was scored using a 4
      point scoring system (3 = normal to 0 = defect), and summed to a regional uptake
      score (RUS). Regional area means the infarcted area in which 99mTc-PYP
      accumulated. The number of decreased uptake segments (ES) was then determined.
      The infarcted area was defined as the area of 99mTc-PYP uptake. RESULTS: The ESs
      for the GIK-201Tl and 18F-FDG-PET images were significantly lower than the number
      of 99mTc-PYP uptake segments. The RUS for GIK-201Tl was higher than that for
      resting-201Tl imaging and similar to those for 18F-FDG-PET. CONCLUSIONS: In the
      detection of myocardial viability following AMI, GIK-201Tl imaging is useful with
      findings similar to those of 18F-FDG-PET.

PMID- 15515745
TI  - Cerebral blood flow abnormalities induced by transient hypothyroidism after
      thyroidectomy--analysis by tc-99m-HMPAO and SPM96.
AB  - The current study is an investigation of alterations in regional cerebral blood
      flow (rCBF) distribution in patients with transient hypothyroidism after
      thyroidectomy. In addition, the effects of thyroxine treatment on rCBF changes
      were studied. METHODS: Noninvasive rCBF measurements using 99mTc-HMPAO SPECT were
      performed on 24 post-thyroidectomy patients who were in a hypothyroidic state.
      The measurements were conducted before 131I therapy and after thyroid hormone
      (thyroxine) replacement. We used adjusted rCBF images (normalization of global
      CBF for each subject to 50 ml/100 g/min with proportional scaling) to compare
      these data with age-matched normal control groups (n =15) using SPM96. We also
      compared the absolute rCBF value of hypothyroidic patients with those of normal
      control groups. In addition, the association between rCBF alteration and the
      severity of depression was also analyzed. Finally, the effect of thyroid hormone
      replacement on rCBF was investigated individually using the Jack-knife test, in
      which patient data were compared with those from healthy volunteers. According to
      the result of this test, all cases were categorized into three subgroups, namely,
      improved, unchanged group and normal. To prove the reversibility of rCBF
      alteration after thyroid hormone replacement, a group comparison test between the
      normal controls and the improved group was done before and after thyroid hormone
      replacement. Similarly a group comparison test between the unchanged group and
      normal controls was also performed. RESULTS: In the hypothyroidic condition,
      there was a significant decrease in the posterior part of the bilateral parietal
      lobes and in part of the bilateral occipital lobes, including the cuneus. These
      decreased rCBF areas extended to the bilateral prefrontal cortices as
      deterioration became more profound. On individual analysis, 16 of 24 patients
      (66.7%) demonstrated rCBF reduction, while 8 patient did not show significant
      rCBF change (33.3%, the normal group). After thyroxine replacement, improvement
      of rCBF was noted in nine of 16 patients (56.3%, the improved group). In seven of
      16 patients (43.7% the unchanged group), the significant low rCBF area remained
      unchanged. Compared with the normal controls, the improved group showed
      significantly decreased rCBF of the bilateral parietal lobe and the occipital
      lobe in the hypothyroic condition. After thyroid hormone replacement, these
      abnormal rCBF areas disappeared. In contrast, in the unchanged group, the
      significant hypoperfusion area became localized but remained. CONCLUSION: 99mTc
      HMPAO SPECT and SPM96 analysis demonstrated a significant rCBF decrease in the
      parietal lobe and part of the occipital lobe in patients with induced transient
      hypothyroidism after thyroidectomy. This phenomenon might contribute to
      understanding of the depressive state. Recovery of rCBF after thyroid hormone
      replacement was confirmed in some patients. However, rCBF improvement did not
      always occur in every patient during the follow up period. The reversibility of
      rCBF in transient hypothyroidism may be dependent on individual characteristics
      during a short-term period.

PMID- 15515746
TI  - Value of technetium scintigraphy and iodine uptake measurement during follow-up
      of differentiated thyroid cancer.
AB  - Measurement of serum thyroglobulin (Tg) levels and I-131 whole body scintigraphy
      (WBS) are used in the follow-up of patients with differentiated thyroid cancer
      (DTC). This study was designed to evaluate the significance of persistent I-131
      uptake in the thyroid bed in patients with DTC following surgery and/or
      radioactive iodine ablation. Tc-99m thyroid scintigraphy (TS) and I-131 thyroid
      uptake (IU) were also performed to determine their clinical impact on patient
      management. PATIENTS AND METHODS: Sixty-two non-metastatic patients (14 men, 48
      women) with a mean age of 44 years (range: 16-75) who had undergone surgical
      thyroidectomy for DTC were evaluated prospectively. All patients had undergone
      technetium and iodine scintigraphy (IS). Although serum Tg levels were measured
      in all patients, IU was available in 36. RESULTS: Tg values were in the range of
      0.2-24 ng/ml (median: 0.2 ng/ml) when patients were in the hypothyroid state. I
      131 WBS detected residual tissue in the neck in 30 patients (48%); however TS was
      positive in only 12 (19%). I-131 uptake in the thyroid bed ranged from 0 to 14%
      (median: 0.1%). Twelve of 13 patients with positive IS and negative TS had uptake
      values < or = 0.3% (p < 0.00001). When IU values were < or = 0.3%, 54% of our
      patients did not have any uptake in the thyroid bed on TS or IS, whereas when IU
      was > 0.3%, 80% of patients had neck uptake on both TS and IS (p < 0.00001).
      CONCLUSION: The results of this study demonstrate that the concordance of IS and
      TS depends on the IU level after suspension of replacement therapy. Measurements
      of IU and TS are of considerable value in evaluating patient response to therapy
      and will substantially reduce the need for repetitive radioiodine scans and
      unnecessary treatment doses in patients with undetectable Tg values.

PMID- 15515747
TI  - A problem in diagnosing N3 disease using FDG-PET in patients with lung cancer-
      high false positive rate with visual assessment.
AB  - OBJECTIVE: To evaluate the accuracy of diagnosing N3 disease using positron
      emission tomography (PET) with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) in
      patients with pulmonary disease. SUBJECTS AND METHODS: Twenty patients diagnosed
      as FDG-PET N3 were enrolled. On FDG-PET, lymph nodes were considered to be
      positive when increased uptake as compared with that of the surrounding
      mediastinum was visually observed, or the mean standardized uptake ratio (SUR)
      was more than 2, 2.5, or 3. On CT, lymph nodes exceeding 1 cm in the shortest
      diameter were regarded as positive. RESULTS: The PET result was true positive
      (TP) in 2 patients and false positive (FP) in 18 with an overall accuracy (OA) of
      10% using visual criteria. Using an SUR of more than 2.5, the result was TP in 2,
      FP in 3, and true negative (TN) in 15, the false negative (FN) in 0, with an OA
      of 85%. CT diagnosis was TP in 2, FP in 9, and TN in 9 with an OA of 55%. The
      accuracy using the SUR criteria of more than 2.5 was superior to that of CT.
      CONCLUSION: Of 20 patients with the diagnosis of PET N3, we found frequent over
      diagnosis in nodal staging using the visual criteria.

PMID- 15515748
TI  - Development of "super rapid dynamic SPECT," and analysis of retention process of
      99mTc-ECD in ischemic lesions: comparative study with 133Xe SPECT.
AB  - To analyze the retention process of technetium-99m ethyl cysteinate dimer (99mTc
      ECD) in normal and ischemic lesions, we developed a super rapid dynamic SPECT
      system based on the CERASPECT (DSI, Inc., Waltham, MA, USA). The system made it
      possible to take a SPECT series every 2 seconds. Each SPECT series contains a
      maximum of 16 slices (6.6 mm slice interval) in a matrix size of 32 x 32. The
      sensitivity of this system is 175 kcps/MBq/ml/cm slice thickness, and resolution
      is 12 mm FWHM at the center of a 20 cm(phi) water phantom. Using the super rapid
      SPECT system, the kinetic behavior of the 99mTc-ECD during retention in normal
      and ischemic lesions was analyzed. Twenty patients with ischemic lesions that
      were clearly demonstrated by 133Xe-rCBF (regional cerebral blood flow) SPECT but
      unclear on static 99mTc-ECD SPECT were examined. For the dynamic SPECT, 700 MBq
      of 99mTc-ECD was injected intravenously, and dynamic SPECT data were acquired
      every 2 seconds during a 90-second period. The serial dynamic SPECT and time
      activity curves at some lesions with reduced rCBF and at the contralateral normal
      brain were analyzed. These dynamic SPECT data were compared with conventional
      static 99mTc-ECD SPECT and quantitative 133Xe-rCBF SPECT. All of mildly or
      moderately reduced rCBF lesions on the 133Xe-rCBF SPECT were recognized as low
      activity regions only at the early phase (during about 2-20 sec or less), with
      the lesions then gradually vanishing. These lesions were not recognized on the
      conventional static SPECT taken after the dynamic study. The time-activity curve
      at the reduced rCBF lesion was lower than that of contralateral normal brain at
      the early phase, and overtook the activity in the normal region with a gradual
      increase. The early phase images of 99mTc-ECD SPECT within 20 seconds by the
      super rapid dynamic SPECT were very useful to the same extent as the 133Xe-rCBF
      SPECT for detecting mild or moderate ischemic lesions. This study suggests that
      esterase activity, participating in the ECD retention mechanism, may be tolerable
      to mild or moderate ischemia. This tolerance may be the main cause of the
      nonlinear relationship between ECD accumulation and cerebral blood flow.

PMID- 15515749
TI  - Value of bone scintigraphy in patients with carpal trauma.
AB  - OBJECTIVE: We planned this study to evaluate the role of bone scintigraphy in
      patients with suspected carpal fracture and normal or suspicious radiographs
      following carpal injury. METHODS: Three-phase bone scintigraphy using Tc-99m-MDP
      was performed on 32 patients with negative radiographs but clinically suspected
      fracture at two weeks after the trauma. Focally increased radiopharmaceutical
      uptake was interpreted as a fracture. The final diagnosis was established with
      clinical follow-up. RESULTS: Twelve (38%) patients had a normal scan excluding
      fracture. Twelve patients had a single fracture. Multifocal fracture was present
      in 8 (25%) patients. Eight patients showed scaphoid fractures; of these three
      showed single scaphoid fracture, and the other five patients revealed
      accompanying fractures. Distal radius fractures and carpal bone fractures other
      than scaphoid were both observed in 12 patients. These were eleven fractures of
      distal radius; three fractures of pisiform; two fractures of hamate; and single
      fractures of lunate, trapezium and triquetrum. In one patient there was fracture
      of a first metacarpal bone. CONCLUSION: In patients with suspected carpal bone
      fracture and normal or suspicious radiographs, bone scintigraphy can be used as a
      reliable method to confirm or exclude the presence of a scaphoid fracture and to
      detect clinically unsuspected fractures of distal radius and other carpal bones.

PMID- 15515750
TI  - Relationship between bone scintigraphy and tumor markers in patients with breast
      cancer.
AB  - PURPOSE: The aim of this study is to specify the precise role of bone
      scintigraphy and serum CEA and CA 15-3 assays in the monitoring of breast cancers
      in order to optimize their use and to determine whether it is possible to guide
      the prescription of bone scan by the use of CEA and CA 15-3 assays in the
      monitoring of breast cancer. METHODS: For this purpose, from November 1997 to May
      2002, 98 consecutive female breast cancer patients (median age, 52 years; range
      35-77 years) underwent bone scintigraphy during follow-up. In these patients
      values of tumor markers were compared with the results of bone scintigraphy. Some
      of the patients with bone metastasis were checked repeatedly at intervals of 6 to
      12 months, resulting in 49 patients with bone metastasis and 74 patients without
      bone metastasis being included in the study. RESULTS: In patients with bone
      metastasis, serum CEA levels were abnormal in 23/49 cases and CA 15-3 serum
      concentrations were elevated above the cut-off in 33/49 cases. Among patients
      without bone metastasis, CEA and CA 15-3 serum concentrations were normal in
      50/74 and 55/74 cases respectively. The combination of the two markers improved
      the diagnostic sensitivity. CONCLUSION: Although serial tumor marker measurements
      are an efficient and cost effective method of monitoring disease progression, it
      does not allow prediction of the bone scan results; so it is not justifiable to
      reject a bone scintigraphy on the basis of these markers.

PMID- 15515751
TI  - Left ventricular ejection and filling rate measurement based on the automatic
      edge detection method of ECG-gated blood pool single-photon emission tomography.
AB  - The objective of the present investigation was to determine the feasibility of
      assessing left ventricular systolic ejection and diastolic filling via the
      automatic edge detection method employing ECG-gated blood pool single-photon
      emission tomography (SPET GBP) data. METHODS: Thirty-five patients, who had
      undergone both SPET GBP and ECG-gated equilibrium blood pool scintigraphy by the
      planar method (planar GBP), were enrolled in this study. Planar GBP was performed
      with a single-headed gamma camera. From the left anterior oblique projection,
      data were acquired at 24 frames/cardiac cycle with ECG-gating during the
      equilibrium state. SPET GBP was conducted utilizing a triple-headed gamma camera,
      with 60 projection views over 360 degrees by 60 sec per view, in 16
      frames/cardiac cycle. In each frame, left ventricular volume was determined by
      automatic edge detection employing a quantitative gated SPET program.
      Additionally, the time-volume curve was fitted by the 4th harmonics of Fourier
      transform. Ejection fraction (EF, %), peak ejection rate (PER, /sec), peak
      filling rate (PFR, /sec) and mean filling rate during the initial one-third of
      diastolic time (1/3 FRm) were calculated from the fitted curve. These parameters
      were also calculated with planar GBP data. RESULT: Left ventricular ejection and
      filling parameters were calculated by SPET GBP with the automatic edge detection
      program for all patient data. Correlation coefficients of EF, PER, PFR and 1/3
      FRm between SPET and planar GBP were 0.91 (p < 0.001), 0.82 (p < 0.001), 0.78 (p
      < 0.001) and 0.74 (p < 0.001), respectively. CONCLUSION: Ejection and filling
      rates can be calculated using SPET GBP with the edge-detection software. These
      parameters displayed significant correlations with those values obtained via
      planar GBP. Additional studies are warranted to determine the reliability of
      parameters with SPET GBP.

PMID- 15515752
TI  - A clinical assessment of the relationship between bone scintigraphy and serum
      biochemical markers in hemodialysis patients.
AB  - BACKGROUND: Renal osteodystrophy is a metabolic bone disease and a common
      complication of end-stage chronic renal failure and maintenance dialysis
      treatment. In this study, we examined the correlation between quantifying bone
      scintigraphy and serum biochemical markers in hemodialysis patients. METHODS:
      Bone scintigraphy with technetium-99m-hydroxy-methylene-diphosphonate (99mTc
      HMDP) was performed on 28 patients on maintenance hemodialysis. Bone scintigraphy
      was performed using a standard protocol and was quantified by setting regions of
      interest (ROIs) over selected regions. The bone-to-soft-tissue ratio (B/ST ratio)
      at each region was calculated in all patients. The B/ST ratios were then compared
      with serum biochemical markers. RESULTS: The B/ST ratio for the skull correlated
      well with serum bone-specific alkaline phosphatase (BAP) (r = 0.735, p < 0.001),
      serum deoxypyridinoline (DPD) (r = 0.806, p < 0.001) and intact parathyroid
      hormone (intact PTH) (r = 0.701, p < 0.001). The B/ST ratio for the lumbar spine
      correlated with intact PTH (r = 0.387, p < 0.05) but not with serum BAP or serum
      DPD. The B/ST ratio for the femoral neck correlated with serum DPD (r = 0.431, p
      < 0.05) and intact PTH (r = 0.449, p < 0.05) but not with serum BAP. CONCLUSIONS:
      Our data suggest that quantitative bone scintigraphy is a sensitive and useful
      method for evaluating bone metabolism in hemodialysis patients. The B/ST ratio
      for the skull may reflect changes of bone metabolism in hemodialysis patients.

PMID- 15515753
TI  - 18F-FDG PET is superior to 67Ga SPECT in the staging of non-Hodgkin's lymphoma.
AB  - OBJECTIVE: Our study aims to compare diagnostic accuracy between 18F-FDG PET and
      67Ga SPECT in the staging of non-Hodgkin's lymphoma. METHODS: Twenty-eight
      patients with non-Hodgkin's lymphoma, underwent 18F-FDG PET, 67Ga SPECT and CT
      for the pretreatment staging of malignant lymphoma between August 1999 and March
      2002. 18F-FDG PET imaging was obtained 60 minutes after the intravenous
      administration of 185 MBq of 18F-FDG. 67Ga SPECT imaging was obtained 2 days
      after the intravenous administration of 148 MBq of 67Ga. 18F-FDG PET and 67Ga
      SPECT were performed within one month. Both imagings were performed on the area
      from the neck to the pelvis. The 18F-FDG PET and 67Ga SPECT findings were
      compared with the CT findings and the clinical course. RESULTS: Sixty-six nodal
      lesions were clinically confirmed. Of these, 32 were identified by both 18F-FDG
      PET and 67Ga SPECT. The remaining 34 lesions were identified only by 18F-FDG PET.
      The mean (+/- SD) sizes' of the nodes were 34.7 +/- 32.4 mm for 18F-FDG-positive
      and 67Ga-positive lesions and 15.7 +/- 8.3 mm for 18F-FDG-positive and 67Ga
      negative lesions (p < 0.001). Of the 23 extranodal lesions, 12 were identified by
      both 18F-FDG PET and 67Ga SPECT, whereas 6 lesions were identified by only 18F
      FDG PET. Five lesions were not identified by either technique. No 18F-FDG
      negative but 67Ga-positive nodal or extranodal lesions were observed. The
      difference in findings between the two studies is related to the difference in
      the size but not in the histology or site of the lesions. CONCLUSION: 18F-FDG PET
      detected significantly more lesions particularly small lesions than 67Ga SPECT.
      Thus, 18F-FDG PET is considered to be superior to 67Ga SPECT in the staging of
      non-Hodgkin' s lymphoma.

PMID- 15515754
TI  - Superimposed dual-isotope SPECT using 99mTc-hydroxymethylene diphosphonate and
      201Tl-chloride to assess cartilage invasion in laryngohypopharyngeal cancer.
AB  - OBJECTIVE: Cartilage invasion in laryngohypopharyngeal cancer has a significant
      impact on the choice of treatment modality and outcome of the disease. We
      examined invasion of cartilage in laryngohypopharyngeal cancer by simultaneous
      bone and tumor dual-isotope SPECT using 99mTc-hydroxymethylene diphosphonate and
      201Tl-chloride. METHODS: Early and delayed simultaneous bone and tumor dual
      isotope SPECT were performed on 19 patients with laryngohypopharyngeal cancer.
      Dual-isotope SPECT images were superimposed to project tumor location from tumor
      SPECT onto the osseous structures shown by bone SPECT. The presence or absence of
      cartilage invasion was evaluated histopathologically or by radiological studies
      such as CT and/or MRI. RESULTS: Histopathological or radiological examination of
      the cartilage revealed invasion in 5 patients and no invasion in 14 patients. The
      results of both early and delayed dual-isotope SPECT were exactly the same. Using
      dual-isotope SPECT, the sensitivity, specificity, and accuracy in detecting
      cartilage invasion by laryngohypopharyngeal cancer were: 80% (4/5), 92.9%
      (13/14), and 89.5% (17/19), respectively. CONCLUSIONS: Results of the present
      study suggest that superimposed early bone and tumor dual-isotope SPECT images
      may be sufficient for the diagnostic evaluation of cartilage invasion by
      laryngohypopharyngeal cancer. Superimposed dual-isotope SPECT imaging is a useful
      technique in the evaluation of cartilage invasion in laryngohypopharyngeal
      cancer.

PMID- 15515755
TI  - Usefulness of measuring the gastric emptying time in a case of brittle diabetes.
AB  - Gastric emptying time measurement by radionuclide study, although quite
      informative, is rarely remembered in clinical practice. We presented a patient
      with brittle diabetes who had multiple emergency admissions due to hypoglycemia
      under routinely prescribed insulin therapy. She had severe gastroparesis, which
      was determined by scintigraphic gastric emptying study (gastric half-emptying
      time = 260 min for a mixed meal). She had not presented to the emergency service
      for two years because of only a slight change the timing of her insulin
      administration time (after meal instead of before meal) in the light of gastric
      emptying study.

PMID- 15515756
TI  - Primary idiopathic chylopericardium: report of two cases.
AB  - Primary chylopericardium is an extremely rare disease. This report presents two
      cases of this disease, in a 47-year-old man and 21 -year-old woman. Both cases
      were given diagnosis of primary chylopericardium by chylous pericardial fluid
      examination and lymphangio-scintigraphy which demonstrated abnormal communication
      between the left thoracic duct and the pericardial cavity.

PMID- 15515757
TI  - Correct localization of epileptogenic focus with I-123 iomazenil cerebral
      benzodiazepine receptor imaging: a case report of temporal lobe epilepsy with
      discordant ictal cerebral blood flow SPECT.
AB  - A 26-year-old female with intractable epileptic seizures was studied with I-123
      iomazenil cerebral benzodiazepine receptor, I-123 IMP inter-ictal and Tc-99m ECD
      ictal cerebral blood flow SPECT. The ictal cerebral blood flow SPECT indicated
      the location of the seizures to be in the left temporal lobe, where increased
      regional cerebral blood flow was noted in marked contrast to the inter-ictal
      SPECT. Ictal electroencephalograms (EEGs) recorded with scalp and sphenoidal
      electrodes also suggested the left temporal lobe as the location of the seizures.
      On I-123 iomazenil SPECT, however, decreased benzodiazepine receptor density was
      demonstrated in the right temporal lobe. MRI showed mild atrophy and abnormal
      signal intensity in the right temporal lobe. Ictal EEGs recorded with
      intracranial electrodes revealed that abnormal electrical activity of the brain
      always emerged from the right temporal lobe and then propagated to the
      contralateral side. Based on the findings of intracranial EEGs, partial resection
      of the right anterior temporal lobe including hippocampus was performed. After
      the surgery, no seizure occurred. Pathological examination of the surgical
      specimens revealed hippocampal sclerosis. This case suggested that cerebral
      benzodiazepine receptor imaging with I-123 iomazenil can be helpful for correct
      localization of epileptogenic foci.

PMID- 15515758
TI  - Brown adipose tissue: evaluation with 201Tl and 99mTc-sestamibi dual-tracer
      SPECT.
AB  - Brown adipose tissue is one kind of adipose tissue and regulates body temperature
      and balance of energy via non-shivering thermogenesis. The authors present a case
      that strongly suggested the presence of activated brown adipose tissue in the
      neck, shoulders and axillary space by increased 18F-FDG uptake. 99mTc-sestamibi
      and 201Tl dual-tracer SPECT study showed increased 99mTc-sestamibi uptake and non
      increased 201Tl uptake in the corresponding 18F-FDG uptake sites. Brown adipose
      tissue has dense mitochondria in the cells, which play an important role in
      thermogenesis. 99mTc-sestamibi uptake and retention depend on the mitochondrial
      activity but 201Tl uptake does not. Therefore, the activity of mitochondria in
      activated brown adipose tissue may explain the discrepant uptake between 99mTc
      sestamibi and 201Tl.

PMID- 15515759
TI  - [Retinal vasculitis].
AB  - Retinal vasculitis is one of the frequently cause of impair of visual acuity. The
      vein is involved most of time, and the artery is involved less. Sometimes, the
      vein and artery are involved together. The types and cause of the disease are
      complex. In recent years, ophthalmologists have gotten some new achievements on
      the study of the disease, and some arguments just like naming, diagnosing and
      treatment still exist. Now we review all the achievement and arguments of the
      naming, clinic, pathology, etiology, experiment, diagnosing, treatment of the
      disease.

PMID- 15515760
TI  - [Expression of vascular endothelial growth factor and its receptors (flt-1) in
      morbid human corneas and investigation of its clinic importance].
AB  - PURPOSE: To investigate the expression of vascular endothelial growth factor
      (VEGF) and its receptor (flt-1) in morbid corneas and the potential effects.
      METHODS: Eleven cases of normal peripheral corneas and limbal tissues and 32
      cases of miscellaneous morbid corneas were collected during corneal
      transplantation. The specimens were sectioned in a cryostat and stained with
      streptavidin-biotin-peroxidase method for VEGF and flt-1. The expressive levels
      of VEGF were compared with grades of patients' clinical manifestations. RESULTS:
      Positive expression of VEGF was exclusively presented in all morbid corneal
      specimens and that of flt-1 was showed in most cases. Stronger staining was found
      in the epithelia and stoma of the morbid cornea. The expressive levels of VEGF
      were more important in the stroma and the endothelia of the morbid corneas than
      that in the normal peripheral corneas and were positively correlated with the
      degrees of corneal opacities and the area of corneal neovascularization in
      infiltrating inflammatory cells and proliferative tissues ( P < 0. 05).
      CONCLUSIONS: VEGF and flt-1 were expressed in miscellaneous morbid corneas and
      may play an important role in the repair of corneal injuries and the corneal
      neovascularization.

PMID- 15515761
TI  - [Effect of ocular accommodation on refractive components in children].
AB  - PURPOSE: To study the correlation between ocular accommodation and ametropia,
      especially myopia by analyzing the effect of accommodation on refractive
      components in children. METHODS: The anterior chamber depth (AD), lens thickness
      (LT), vitreous chamber length (VL) and ocular axial length (AL) were measured for
      135 cases (270 eyes) of children before and after cycloplegia. The corneal shapes
      of 136 eyes selected from the 270 eyes were studied before and after cycloplegia
      by a computerized video keratoscope. RESULTS: AD increased (P < 0. 001) while
      both LT (P < 0. 001) and VL decreased (P < 0. 01) significantly after cycloplegia
      regardless of their refractive state. However, AL increased for hyperopic eyes (P
      = 0.027) and decreased for myopic eyes (P = 0.008) after cycloplegia. For
      hyperopic eyes, the major keratometer K1 increased (P = 0.025) while for myopic
      eyes, the major keratometer K1 (P = 0.039) and minor keratometer K2 (P = 0.003)
      decreased after cycloplegia. Similarly, mean corneal power of zones 3 mm (MD3), 5
      mm (MD5) and 7 mm (MD7) decreased dramatically (P < 0.05) with myopic eyes after
      cycloplegia, while MD3 (P = 0.009) increased with hyperopic eyes. The mean
      refractive power of the lower half vertical meridian (LMD) is greater than that
      of upper half (UMD); and the mean refractive power of the lateral half of the
      horizontal (LaMD) is greater than that of the medial half (MMD). CONCLUSION: The
      ocular accommodation has a great influence on refractive components in children.
      It is not only the process by which the refractive power of the lens is
      increased. Furthermore, the lens itself moved forward relatively. There is
      asymmetry of the corneal surface within the same horizontal or vertical meridian.

PMID- 15515762
TI  - [The state of diopter and visual acuity in central serous chorioretinopathy].
AB  - PURPOSE: To investigate the state of diopter and best corrected visual acuity in
      active central serous chorioretinopathy (CSC). METHODS: Twenty-three unilateral
      active CSC patients (23 eyes) were observed with Integrated Optometry Apparatus.
      The period of follow-up was from 3 - 12 months (mean, 7.2 months). RESULTS: Of
      the 23 patients, 15 eyes (65.2%) of active CSC and 5 fellow eyes (21.7%) showed
      hyperopic state. There were significant differences in hyperopic state between
      the active eyes and fellow eyes (P < 0.01). After follow-up, there were only 5
      eyes of CSC (21.7%) showed slight hyperopia. There were significant differences
      in hyperopic state between before and after follow-up of the eyes of CSC (P <
      0.01) Among the eyes of the best corrected visual acuities were increased 3 row
      or above, 90.9% eyes of the best corrected visual acuities were resumed to 1.0.
      CONCLUSION: Most of the active CSC demonstrated temporary hyperopic state due to
      the neuroretinal detachment of macula. The best corrected visual acuities with
      the Integrated Optometry Apparatus in active CSC are useful in evaluating the
      final visual acuities of the eyes.

PMID- 15515763
TI  - [Primary implantation of posterior chamber intraocular lens in eyes with
      posterior capsulorhexis].
AB  - PURPOSE: To evaluate the effect of anterior vitrectomy combined with primary
      implantation of posterior chamber intraocular lens for the capsulorhexis
      following cataract extraction. METHODS: Anterior vitrectomy combined with primary
      implantation of posterior chamber intraocular lens was performed on 76 cases with
      capsulorhexis from 1 089 cases of cataract extraction. The surgical technique,
      postoperative visual acuity and postoperative complication were analyzed.
      RESULTS: The proportion, of which the corrected visual acuity was 0.5 or better
      one week and six months postoperatively, was 86.8% and 93.4% respectively.
      CONCLUSION: Anterior vitrectomy combined with primary implantation of intraocular
      lens for posterior capsulorhexis following cataract extraction is safe and
      effective.

PMID- 15515764
TI  - [Clinical observation on fresh amniotic membrane transplantation for treatment of
      recurrent pterygium].
AB  - PURPOSE: To observe the effect of retrograding excision of pterygium with
      amniotic membrane transplantation on the prevention of pterygium relapse.
      METHODS: Incisions of conjunctiva were made along both sides of pterygium body.
      The conjunctiva was then separated from the underlying pterygium tissue and cut
      at the side of pterygium body. It was further separated from the underlying
      pterygium tissues toward the caruncle so that the pterygium tissue could be
      exposed, which was separated from the sclera and then was excised at the site of
      the plicae semilunaris and separated from the cornea retrogressively. The exposed
      sclera was then covered by transplanted amniotic membrane. RESULTS: After 6 - 19
      months of follow-up, two in 60 eyes of pterygium relapsed, recurrent rate 3. 3%.
      No immune rejection, necrosis and graft absorption were found. CONCLUSION:
      Retrograding excision of pterygium with fresh amniotic membrane transplantation
      can significantly decrease the relapse of pterygium. Amniotic membrane
      transplantation is a reasonable method for treatment of pterygium. Fresh amniotic
      membrane transplantation has advantages of easily obtain, convenient usage, and
      lower cost, which is suitable in local hospital of our country.

PMID- 15515765
TI  - [Application of small incision sutureless surgery in cataract].
AB  - PURPOSE: To explore the advantages of nuclear manual-chop technique in small
      incision cataract surgery. METHODS: By randomly sampled, post-operative visual
      acuity, corneal astigmatism and complications (one month of follow-up) of 120
      eyes of small incision sutureless surgery associated with nuclear manual-chop
      were compared to that of 80 eyes of traditional ECCE with IOL implantation.
      RESULTS: Visual acuity of 112 eyes (93.3% ) of small incision group in one week
      postoperatively was increased 0.5 above compared to that of 48 eyes (60%) of ECCE
      group. The difference was statistically significant (chi2 = 4. 73, P < 0.05). In
      small incision group, the corneal astigmatism was (1.01 +/- 0.97) D (n = 95) in
      one week postoperatively and (0.62 +/- 0.53) D (n = 90) in one month
      postoperatively. A significant difference existed between the small incision
      group and ECCE group (t = 3.1467, P < 0.01 and t = 3. 4753, P < 0.01). As for
      post-operative complications, in small incision group, one post-capsule rupture
      was recorded. CONCLUSION: Small incision sutureless surgery with manual-chop
      technique is worth developing and spreading because of its advantages.

PMID- 15515766
TI  - [Clinical comparison of the Tono-Pen tonometer to the Goldmann applanation
      tonometer].
AB  - PURPOSE: To compare the Tono-Pen tonometer with the Goldmann applanation and
      assess the precision and accuracy of the Tono-Pen tonometer. METHODS: 62 cases
      (111 eyes) were random measured with the Tono-Pen tonometer and the Goldmann
      applanation tonometer. RESULTS: Overall we found that 74.8% of the Tono-Pen
      readings were within +/- 2 mmHg of the Goldmann applanation readings and 83.8%
      were within +/- 3 mmHg. The correlation coefficient between the readings of the
      two instruments was 0.865. The mean value of the paired differences was (-0.51 +/
      2.24)mmHg in the 9 to 30 mmHg interval. CONCLUSION: The Tono-Pen tonometer
      measures intraocular pressure in a manner that corresponds well to the Goldmann
      applanation tonometer, especially in the 9 - 30 mmHg interval. But this tonometer
      may overestimate the intraocular pressure in eyes with low intraocular pressure,
      and underestimate the intraocular pressure in eyes with high intraocular
      pressure.

PMID- 15515767
TI  - [To establish and observe the experimental lens regeneration model in rabbits].
AB  - PURPOSE: To establish the lens regeneration model in New Zealand rabbits, observe
      the lens regeneration process to investigate the mechanism of lens epithelial
      cell growth and lens regeneration. METHODS: Lens extraction by endocapsular
      phacoemulsification was performed on 8 experimental eyes in New Zealand albino
      rabbits weighing approximately 1.5 - 2.5 kg. To restore a relative intact capsule
      bag, a little needle tip was inserted through the limbal wound to perform a 2 mm
      lined anterior capsulotomy, which just permitted the insertion of a 21G
      phacoemulsification tip. Phacoemulsification extraction was applied to remove all
      lens cortical material and then Healon was injected intracapsularly to distend
      the capsule bag. With slitlamp, the procedure of le ns regeneration were observed
      and taken photographs. A histologic study on regenerated lens were also
      performed. RESULTS: The relative 3 different results on experimental eyes
      according to the size of anterior capsulotomy in surgical procedure. In 4 eyes,
      when the size of anterior capsulotomy is approximately 2 mm and the capsule bag
      is relatively intact, lens regeneration occured and it has a relatively normal
      translucent cortex and central nuclear opacity. Among other 4 surgical eyes, the
      lower half part of lens regeneration was still observed in one eye though the
      upper half of anterior capsule was damaged, whereas in other 3, owing to the
      whole anterior capsule lack nearly, lens regrowth was not noted in areas of pupil
      under the slitlamp biomicroscopy observation and the posterior capsule appeared
      as gray-white membrane opacity. Histologic study showed that lens epithelial
      cells in equatorial zone proliferate and differentiate into lens fibers and
      continues to refill the whole capsule bag. Lens fiber alignment was regular in
      the periphery of regenerated lens, whereas in the center opacity nuclear, the
      bulk of the regenerated lens material consisted of an eosinophilic disorganized
      lens fibers. In addition, there were much of irregular cellular proliferation in
      capsule wrinkling. CONCLUSION: Capsule is the support material of lens epithelial
      cells regrowth. Lens regeneration occurred in rabbits after restoring lens
      capsular integrity following endocapsule phacoemulsification lens extraction,
      which was the result of the lens epithelial cells proliferation and
      differentiation. The cellular proliferation and differentiation was associated
      with the of capsule morphosis.

PMID- 15515768
TI  - [Effects of Schwann cell-derived neurotrophic activity on cultured retinal
      ganglion cells survive and grow in normal and gas-deprived environment].
AB  - PURPOSE: To investigate the effects of Schwann cell-derived neurotrophic activity
      (SCNA) on cultured retinal ganglion cells (RGC) survive and the expression of
      growth associated protein 43 (GAP43) in normal and gas-deprived environment.
      METHODS: Schwann cells of new born SD rat were cultured, and remaded it into
      solutions containing different concentrations of SCNA. Then these solutions were
      added to the primarily cultured retinal cells, the activity of SCNA was
      determined by MTT method. The fluro-gold retrolabelled retina cells of 3d new
      born rats were cultured and plated on 24 well culture plate. At the 2rd day of
      culture, 300 mg/L SCNA were added into the medium of SCNA group. At the 5th day,
      liquid paraffin was added on the surface of medium of air deprived groups to lead
      an air deprived injury. Cultured for 12h, the liquid paraffin was discarded off,
      and then we observed the morphology and counted the fluro-gold labeled RGC. The
      effects of SCNA on the expression of GAP43 in cultured retinal cells were
      identified by Western Blot. RESULT: SCNA could promote the survival of RGC in a
      protein concentration-dependent manner. Added SCNA to the medium, the retinal
      cells grown much better and had less floating dead cells. The number of RGC was
      also significantly more than the control (F = 62.89, P < 0.01). The cells of air
      deprived group had showed swelling change. But the cells of group with SCNA are
      less affected and the number of RGCs is significantly different from the control
      (F = 49.27, P < 0.01). The expression of GAP43 in normal and air deprived groups
      with SCNA were up-regulated. CONCLUSION: SCNA has significantly neurotrophic
      effect on cultured RGC and increases the expression of GAP43. Added SCNA to the
      medium could reduce the injury of air deprived and promote RGC survival rate in
      this kind of injury environment.

PMID- 15515769
TI  - [Effects of hypericin on traumatic proliferative vitreoretinopathy in rabbits].
AB  - PURPOSE: To examine the effects of hypericin on traumatic proliferative
      vitreoretinopathy (PVR) in rabbits. METHODS: Traumatic PVR was induced in
      pigmented rabbits by intravitreal injection of platelet rich plasma.
      Subsequently, the eyes received an intravitreal injection of saline (0.1 ml), or
      hypericin (0.1 ml) in doses of 1 microM, 10 microM and 100 microM. The eyes were
      examined ophthalmoscopically on distinct days after surgery and the stage of PVR
      was evaluated. RESULTS: In the control eyes, the retina was detached after 10
      days, the PVR had progressed to higher stages over time. In the eyes injected
      with hypericin, the PVR also developed, however, the severity of PVR on each day
      was lower than that in control eyes on that day. PVR was significantly inhibited
      in groups treated with 10 and 100 microM hypericin as compared with the control
      eyes after 5 days (P < 0.05). Histological examination of the hypericin-treated
      eyes disclosed no morphological changes, and ERG analysis revealed no significant
      functional changes. CONCLUSION: Intravitreal injection of hypericin is a safe and
      effective means of reducing traumatic PVR as an initial step in exploring its
      potential for clinical treatment of PVR.

PMID- 15515770
TI  - [The study of immunofluorescence on the retinal digest preparations].
AB  - PURPOSE: To study the technique of immunofluorescence staining on the digested
      retina preparations. METHODS: Retinas of 5 normal Wistar rats and 5 STZ diabetic
      Wistar rats of were used to make digested retina preparations and carry out
      immunofluorescence staining with the vascular cell adhesion molecule-1 (VCAM-1).
      RESULT: The retinal vessels were clearly observed; There were a lot of positive
      cells in the retinal preparations of the diabetic Wistar rats, while there were
      no positive cells in the retinal preparations of the normal rats. CONCLUSION: It
      is feasible to carry out immunofluorescence staining on the digested retina
      preparations.

PMID- 15515771
TI  - [Effect of adenovirally delivered brain-derived neurotrophic factor on superoxide
      dismutase within the retina of experimentally injured optic nerve of rat eyes].
AB  - PURPOSE: To study the changes of malondialdehyde(MDA) and superoxide dismutase
      (SOD) in the retinal tissues of the rats after optic nerve injury and the
      influence to it by adenovirally delivered brain-derived neurotrophic factor
      (BDNF) to ocular tissues. METHODS: Adenovirus with BDNF gene, adenovirus with
      beta-galactosidase gene and balanced salt solution were injected, respectively,
      into vitreous of injured eyes of rat. The content of MDA and SOD in the retinal
      tissues of the rats were measured by means of quantity analysis in various time.
      That of normal retinal tissues were examined and used as control. RESULTS: The
      content of MDA and SOD in the normal retina was (5.33 +/- 1.45) nmol/ ml (21d),
      fewer than the two control groups' and the contents of SOD of BDNF group were
      (1587.55 +/- 173.39) U/g x pro (3d), (1613.24 +/- 184.57) U/g x pro(7d) (1694. 49
      +/- 184. 30) U/g x pro (14d) and (1721.75 +/- 179.86) U/g x pro(21d), more than
      the two control groups' meanwhile. There were significent differences at 3d, 1 wk
      and 2 wk (P < 0.05). There were no significent differences between the two
      control groups at every time point. CONCLUSION: Adenovirally delivered BDNF to
      murine ocular tissues after optic nerve injury helps protect from oxidative
      stress during earlier period. The effect may be related to the increased amount
      of SOD within local tissue by BDNF.

PMID- 15515772
TI  - [The study on binocular visual field summation and its possible mechanism].
AB  - PURPOSE: To observe the summation effect of binocular visual field in persons
      with normal or abnormal visual field and study the validity of four kinds of
      theory (best eye, average eye, best location, binocular summation) on binocular
      visual field formation. METHODS: The monocular and binocular visual field were
      tested in 15 cases with normal visual field and 58 cases of different kinds of
      ocular diseases with abnormal visual field. RESULTS: The mean rates of summation
      in normal visual field group and abnormal group were 93.00% and 93.10%
      respectively with no significant difference (P > 0.05). The mean degree of
      binocular visual field summation of normal visual field group was 7.05. The
      abnormal group had a greater variation of summation degree than that of normal
      group. The comparison of four theoretic simulating mathematical methods with the
      tested mean retinal sensitivity (MS) of binocular visual field in both groups
      showed minimum difference between the MS calculated by the model of best location
      and the actual MS value. CONCLUSIONS: Binocular summation is a common vision
      phenomena. In the four kinds of theory on binocular visual field formation, the
      model of best location can best reveal the phenomena of binocular visual field
      summation.

PMID- 15515773
TI  - [The analyse and nursing of the early complications after non-penetration
      trabecullar surgery combined with implant].
AB  - PURPOSE: To improve the prevention and nursing of complications after non
      penetration trabecullar surgery (NPTS) combined with the implant. METHODS: 25
      patients (35 eyes) were observed and nursed after they underwent NPTS combined
      with reticulated hyaluronic acid implant. RESULTS: In 35 eyes, the flat anterior
      chamber I occurred in 3 eyes, the flat anterior chamber 11 occurred in 2 eyes,
      and 2 eyes had hyphema in early period after operation. CONCLUSION: It is
      important to the success of operation that postoperative complications are
      detected timely, managed and nursed properly.

PMID- 15515774
TI  - The menacing pulmonary artery aneurysms of Behcet's syndrome.

PMID- 15515775
TI  - Therapeutic approaches to familial Mediterranean fever. What do we know and where
      are we going to?

PMID- 15515776
TI  - Infliximab in refractory uveitis due to Behcet's disease.
AB  - OBJECTIVE: To report 4 cases of refractory panuveitis due to Behcet's disease
      treated with a novel therapy: infliximab. METHODS: Retrospective study of 3 women
      and 1 man of Causasian origin with Behcet's disease complicated with panuveitis.
      Their uveitis was relapsing from 48 to 96 months and was resistant to the
      combination of colchicine (n = 4), high-dose prednisone (n = 4), pentoxyphilline
      (n = 2) and various immunossuppressors and/or immunomodulators given
      successively: intravenous cyclophosphamide (n = 4), azathioprine (n = 3),
      interferon alpha (n = 3), cyclosporine A (n = 2), oral cyclophosphamide (n = 1),
      mycophenolate mofetil (n = 1), methotrexate (n = 1), high-dose immunoglobulin (n
      = 1). Combination with respectively 1, 3, 4 and 5 immunossuppressors and/or
      immunomodulators failed before institution of infliximab. After informed consent
      was obtained, infliximab was administered as a single infusion of 5 mg/kg
      (maximum dose: 400 mg) at day 1, at week 2, 6 and then every 8 weeks. RESULTS:
      With a follow-up ranging from 7 to 22 months, infliximab was efficient in all
      cases. The mean prednisone dose decreased from 45 mg to 13 mg daily. Total
      recovery of visual acuity was observed in half of the cases. Infliximab was well
      tolerated without fever, severe sepsis or autoimmune manifestation. CONCLUSION:
      Infliximab may be efficient in refractory uveitis due to Behcet's disease. The
      optimal dose, rhythm and duration of infliximab infusions need to be
      standardized.

PMID- 15515777
TI  - Serum soluble CD30 levels in Behcet's disease.
AB  - Behcet's disease is associated with the inflammatory response. Several reports
      indicate the presence of primarily CD4+ T cells of the Th1 subtype in the
      inflammation process of the disease. Serum soluble CD30 (sCD30) is reported to be
      released from CD4+ Th2 type cells and has been suggested to be a marker of Th2
      activity. In this study, serum sCD30 levels were measured in active and inactive
      patients with Behcet's disease, healthy controls and a group of patients with
      rheumatoid arthritis, typical Th1 disorder using enzyme immunoassay kit. Mean
      sCD30 value of 54 active patients were found significantly higher than in those
      of 17 inactive patients (p = 0.027), 20 healthy controls (p = 0.040) and 25
      patients with rheumatoid arthritis (p < 0.001). There was a significant
      correlation between increased sCD30 levels and clinical activity index in active
      patients with Behcet's disease. High serum levels of sCD30 may reflect the
      activation of CD4+ T cells or a subset of them in active BD patients. In addition
      to serum sCD30 levels, measurements of the Th2 cytokines may be a helpful tool
      for the evaluation of Th2 activity in Behcet's disease.

PMID- 15515778
TI  - Validation of the classification criteria commonly used in Korea and a modified
      set of preliminary criteria for Behcet's disease: a multi-center study.
AB  - OBJECTIVE: Recently we have proposed a modified set of criteria to settle the
      questions raised regarding the International Study Group (ISG) criteria for
      Behcet's disease (BD). The aim of the present study was to validate the two pre
      existing criteria sets commonly used in Korea, the ISG criteria and the criteria
      of the Behcet's Disease Research Committee of Japan (Japanese criteria), as well
      as the proposed modified criteria. METHODS: The study population included 155
      consecutive patients with BD and 170 controls with non-Behcet's rheumatic
      diseases. Detailed data for all of the subjects were recorded prospectively by
      the participating physicians on a standard form that listed the clinical features
      of BD. The sensitivity, specificity, and accuracy of each set of the criteria
      were measured. RESULTS: Of the three criteria sets employed, the modified
      criteria were the most accurate, with an accuracy of 96.3%. The ISG criteria
      often failed to classify the following patients with BD: patients with only oral
      and genital ulcerations, certain patients with intestinal ulcerations, patients
      who did not manifest oral ulcerations, and patients with acute disease but fewer
      than three recurrent oral ulceration relapses in a 1-year period. The Japanese
      criteria also failed to categorize the following patients with BD: patients with
      oral and genital ulcerations, and patients with oral ulcerations, skin lesions,
      and a positive pathergy reaction. In addition, the Japanese criteria
      misclassified some of the control subjects with non-Behcet's uveitis as having
      BD. CONCLUSIONS: The results of this study suggest that there are some points
      that need to be reconsidered in the clinical application of the two pre-existing
      sets of criteria. Although the modified criteria were the most accurate, further
      validation studies will be required in other ethnic populations.

PMID- 15515779
TI  - The prevalence of familial Mediterranean fever in the Turkish province of
      Denizli: a field study with a zero patient design.
AB  - OBJECTIVE: This study had two aims: (1) to investigate the prevalence of familial
      Mediterranean fever (FMF) and Behcet's disease (BD) in school students in
      Denizli, a province in western Turkey; and (2) to determine whether the
      previously suggested "zero patient design" was reliable for use in a prevalence
      survey. METHODS: The field survey was performed in two stages. In the first stage
      7,389 students (3,847 females and 3,542 males) were asked to fill out a
      questionnaire in the classroom. In the questionnaire, filtering questions for FMF
      (the presence of recurrent attacks of fever accompanying abdominal pain, joint
      pain/swelling, and/or chest pain) and BD (presence of aphthous stomatatis) were
      asked. The second stage consisted of two parts. In the first, 3225 questionnaires
      were completed by 1778 female and 1447 male students calculated according to the
      zero patient design, who were selected randomly from among 7389 students for
      evaluation. Students with any suspicion of FMF and Behcet's disease were called
      to the hospital for detailed investigation. In the second step the remaining
      students were evaluated. RESULTS: Out of 3225 children questioned in the first
      step, 156 claimed recurrent abdominal pain and/or chest pain, and/or joint
      pain/swelling with accompanying fever, which might suggest the presence of FMF
      However, this diagnosis was excluded after further clinical evaluation. In the
      second step 152 students were called for detailed investigation: 2 patients, one
      10 years and the other 12 years old, were diagnosed as having FMF. None were
      diagnosed to have Behcet's disease. CONCLUSION: The prevalence of FMF in Turkey
      in general is about 0.093%. The prevalence rate found in this survey was lower
      (0.027%) which may be due to the historic background of the region. This is the
      first study that has shown that the "zero patient design" can be used in an
      epidemiological survey.

PMID- 15515781
TI  - Levels of interleukin-6 (IL-6) and its soluble receptor (sIL-6R) in familial
      Mediterranean fever (FMF) patients and their first degree relatives.
AB  - OBJECTIVE: Familial Mediterranean Fever (FMF) is a hereditary disease
      characterized by recurrent inflammatory attacks. A subclinical inflammation may
      persist in periods between the attacks and heterozygotes may have higher than
      normal levels of acute phase proteins. We investigated the levels of interleukin
      6 (IL-6) and its soluble receptor (sIL-6R) in FMF patients and their obligatory
      carrier relatives. METHODS: Serum levels of IL-6 and sIL-6R were measured during
      acute attacks (n = 18) and in attack-free FMF patients (n = 26), obligatory
      carriers of FMF (n = 17) and normal controls (n = 11). RESULTS: The median levels
      of IL-6 were significantly higher (45.71 pg/ mL, p = 0.001) during acute attacks
      of FMF only, and were normal (0.01 pg/ mL) in the other groups studied. There was
      no statistically significant difference in the median sIL-6R values between any
      of the groups (p = 0.22). CONCLUSION: IL-6 was extremely elevated during FMF
      attacks but could not detect hypothetical "subclinical" inflammation during
      attack-free intervals or in the heterozygote relatives of patients. Serum levels
      of sIL-6R were comparable in all four groups.

PMID- 15515780
TI  - Increased frequency of familial Mediterranean fever in Central Anatolia, Turkey.
AB  - OBJECTIVE: It has been observed that familial Mediterranean fever is more
      prevalent among people coming from central Anatolia in Turkey. To test this
      observation the frequency of FMF was investigated by afield survey in Sivas, a
      city located in central of Turkey. METHODS: The survey was conducted in a cohort
      of 4809 persons selected by systematic sampling from 2 districts of Sivas, with a
      total population of 83,274. Face to face interviewing was done with registered
      households using a standard questionnaire developed to screen FMF A second
      interview was conducted by a rheumatologist and an internist of those individuals
      who were regarded to have possible FMF. RESULTS: The suspicion of FMF emerged in
      the cases of 46 individuals during the survey and 36 were interviewed for a
      second time. FMF was diagnosed in 10 cases. Only one had a previous diagnosis of
      FMF. The overall frequency of FMF among a cohort of 3,948 inhabitants of Sivas
      was 1/395 (0.25%). CONCLUSION: This study indicates that the prevalence of FMF in
      Sivas may be higher than that in general Turkish population, which has been
      reported to be 0.1%.

PMID- 15515782
TI  - The effect of interferon alpha administration on acute attacks of familial
      Mediterranean fever: A double-blind, placebo-controlled trial.
AB  - BACKGROUND: About a quarter of familial Mediterranean fever (FMF) patients are
      partially or totally resistant to colchicine. A previous observation reported
      that acute attacks may be shortened by administration of interferon alpha (IFN).
      OBJECTIVE: We designed a double-blind, placebo-controlled trial to test our
      initial observations of a beneficial response with IFN in FMF attacks. METHODS:
      We treated 34 acute abdominal attacks with IFN 5 million IU or placebo sc in the
      early phase of the attack. Leucocytes, thrombocytes, the erythrocyte
      sedimentation rate, fibrinogen, C-reactive protein (CRP), serum amyloid A protein
      (SAA), haptoglobin, transferrin, IL-1beta and TNF-alpha were measured at hours 0,
      6, 12, 24 and 48. RESULTS: The median time to recovery in those treated with IFN
      and placebo was not significantly different, while the leucocytosis and high
      levels of fibrinogen were significantly more prolonged in placebo-treated
      patients. CRP and SAA were extremely elevated and peaked at 24h, remaining less
      marked in the IFN-treated patients but the difference was not statistically
      significant. Observations regarding the other parameters were unremarkable.
      CONCLUSIONS: Although there were some clues indicating a depressed inflammatory
      response with IFN, we could not demonstrate a definitive effect of this agent in
      this double-blind trial. The drug may suppress the acute inflammation of FMF only
      if administered at the earliest phase. CRP and SAA may be more sensitive
      indicators of an attack than ESR or fibrinogen.

PMID- 15515783
TI  - The efficacy of continuous interferon alpha administration as an adjunctive agent
      to colchicine-resistant familial Mediterranean fever patients.
AB  - OBJECTIVE: About 10-20% of familial Mediterranean fever (FMF) patients are
      resistant to regular colchicine treatment and have painful recurrent attacks due
      to polyserositis. In clinical practice there is no alternative drug for such
      patients. In a previous pilot study on a small number of colchicine-resistant
      patients, interferon-alpha (IFN-alpha) was administered when painful attacks were
      about to occur. METHODS: In this study we gave IFN-alpha continuously to 8
      colchicine-resistant FMF patients in a schedule while the colchicine therapy had
      been continued. All those patients were complicated with vasculitis or arthritis
      or together during the FMF course. Those complications were treated with the
      other immunosuppressive drugs. While they were under intense immunosuppressive
      therapy, the abdominal and the other serosal attacks remained to continue.
      RESULTS: After the administration of IFN-alpha therapy only one out of eight
      patients had abdominal painful attacks in twice, and one patient had arthritis in
      knees and ankles, the others responded well. Observed side effects were generally
      mild and acceptable. CONCLUSION: Continuous IFN administration in addition to the
      regular colchicine treatment may be useful for the colchicine-resistant attacks
      in FMF patients.

PMID- 15515784
TI  - The level of soluble Granzyme A is elevated in the plasma and in the
      Vgamma9/Vdelta2 T cell culture supernatants of patients with active Behcet's
      disease.
AB  - OBJECTIVE: Gramzyme A (GrA) is a serine proteinase with trypsin-like activity
      that is released extracellularly during the degranulation of cytotoxic cells.
      Among the cytotoxic cells, gamma/delta T cells participate in the early phases of
      the immune response and are known to express perforin and granzymes
      constitutively in agreement with their cytolytic pontential. METHODS: GrA
      activity was detected using the synthetic substrate N-alpha-benzyloxycarbonyl-L
      lysine thiobenzyl ester in the plasma and supernatants of peripheral blood
      mononuclear cell cultured in the presence of Dimethylallyl pyrophosphate to
      obtain Vgamma9/Vdelta2 T cell expansion. RESULTS: Significantly high levels of
      GrA were found in the serum and supernatants of lymphocytes from patients with
      active Behcet's disease cultured in the presence of DMAPP. Levels were found to
      be significantly lower after remission. A positive correlation was observed
      between GrA levels in the supernatants and the Vgamma9/Vdelta2 T cell expansion
      factor. CONCLUSION: These results strongly suggest that Vgamma9/Vdelta2 T cells
      are active participants in the pathogenesis of the disease through their
      degranulation and granzyme release.

PMID- 15515785
TI  - Common Crohn's disease-predisposing variants of the CARD15/NOD2 gene are not
      associated with Behcet's disease in Turkey.
AB  - OBJECTIVE: There are many extra-intestinal findings of Crohn's disease (CD), such
      as oral and genital ulcers, erythema nodosum, uveitis and arthritis, resembling
      the manifestations of Behcet's disease (BD). It is also very difficult to
      distinguish the gastrointestinal involvement of BD from that of CD in some
      patients. Hence, this study aimed to investigate a possible involvement of the
      common CD-predisposing CARD15 variants in the genetic susceptibility to BD.
      METHODS: The study group consisted of 85 consecutive patients with BD (51 male,
      34 female) of Turkish origin. Two of them had intestinal involvement. A group of
      100 ethnically matched, non-related healthy volunteers were used as controls. All
      individuals were genotyped for 3 common CARD15 variants (R702W, G908R, and
      Ll007fsinsC) using a polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) method. RESULTS: None of the three CARD15 variants
      predisposing to CD was observed in patients with BD, including two patients with
      intestinal involvement. The R702W mutation was observed in I healthy chromosome,
      and the 3020insC mutation in 2 chromosomes. No individual was found to be
      homozygous or compound heterozygous for these variants. CONCLUSION: These
      findings suggest that 3 most common CD-predisposing CARD15 variants do not
      constitute a genetic susceptibility factor for BD in Turkey. Further studies
      would be helpful to rule out a possible contribution of other rare or unknown
      variants and/or the effects of different ethnic backgrounds.

PMID- 15515786
TI  - Prevalence of Behcet's disease in rural western Turkey: a preliminary report.
AB  - OBJECTIVES: To study the prevalence of Behcet's disease (BD) in a rural area of
      Western Turkey. METHODS: This study was conducted in seven villages in the rural
      Havsa region which has a total population of 5727. The physicians and medical
      students visited every household and distributed a questionnaire on the symptoms
      of rheumatic disorders. One of the questions was whether they had ever suffered
      from mouth ulcers. If the response was affirmative the proband was examined by a
      rheumatologist and a dermatologist for other symptoms. The individuals with true
      aphthous ulcerations had pathergy tests and were invited to the hospital for
      ophtalmic examinations. RESULTS: Of the 5203 individuals who participated in this
      survey, 4861 were 10 years or older. 124 out of 190 individuals who responded
      positively to the question regarding the presence of mouth ulcers had true
      aphthous ulcerations. 115/124 underwent a pathergy test and 4 showed positive
      reactions without any other stigmata of BD, except for folliculitis in one. Among
      the individuals with a negative pathergy test, 2 had acneiform skin lesions and 1
      a genital ulcer. No individual exhibited any ocular symptoms or findings
      characteristic for BD. Only 1 person with aphthous ulceration, folliculitis and a
      positive pathergy test was considered to have BD. CONCLUSION: In this survey, the
      prevalence of BD was found to be 2: 10,000 (95% confidence interval 0 to 4.3:
      10,000). This figure is lower than what has been reported in four previous
      studies from different regions in Turkey. This finding might be due to ethnic
      distribution and geographical differences.

PMID- 15515787
TI  - Urine leukotriene B4 in familial Mediterranean fever.
AB  - OBJECTIVE: To determine urinary leukotriene B4 (LTB4) levels and their role in
      FMF: METHODS: Urinary LTB4 levels were studied using a commercial ELISA kit in 12
      FMF patients during abdominal attacks, and 20 FMF patients during remission.
      RESULTS: Urinary LTB4 levels in FMF patients during attacks were comparable to
      those during remission, but higher than normal levels (p = 0.03). CONCLUSIONS:
      These findings suggest a persistent activation of the leukotriene pathway in FMF.
      Whether elevated LTB4 levels are the cause or the effect of inflammation is yet
      to be determined.

PMID- 15515788
TI  - T and NK cell subset changes with microbial extracts and human HSP60-derived
      peptides in Behcet's disease.
AB  - OBJECTIVE: Microorganisms such as streptococcus and autoantigens such as 60 kD
      heat-shock protein (HSP60) are implicated in the etiopathogenesis of Behcet's
      disease (BD). METHODS: Peripheral blood mononuclear cells from patients with BD
      (n = 16) and healthy controls (HC) (n = 11) were cultured for 5 days with
      extracts of S. sanguis-KTH-1 (SS), E. coli (EC) and a mixed peptide combination
      from human HSP60 (aa 136-50, 179-97, 224-58 and 336-51) reported to be associated
      with BD. T and NK cell subset changes were determined by flow cytometry. RESULTS:
      In unstimulated 5-day cultures gammadelta+ (both CD4+gammadelta+ and
      CD8+gammadelta+), CD8+alphabeta+, CD4+CD56+ and CD8+CD11b+ cells were increased
      in BD compared to HC. In antigen-stimulated cultures of BD patients CD3+ and
      alphabeta+ T cells responded to HSP60 peptides whereas EC stimulated only CD16/
      CD56+ NK cells. In the control group, similar to BD, alphabeta+ and CD4+ T cells
      responded to HSP60 peptides, however SS and EC mainly activated cytotoxic T cell
      subsets (CD8+CD11b and CD4+CD56+ T cells). CONCLUSION: Significant increases in
      unstimulated T cell subsets suggest the presence of an in vivo T cell activation
      in BD. In both patients and controls similar patterns of responses were observed
      against different microorganisms, however the role of human HSP60 peptides as
      immunodominant, crossreactive antigens could not be demonstrated.

PMID- 15515789
TI  - Is Hughes-Stovin syndrome Behcet's disease?
AB  - Hughes-Stovin syndrome (HSS) is a rare clinical disorder, which has been
      described as the presence of pulmonary artery aneurysm in the setting of systemic
      thrombosis. The term "Incomplete Behcet's Disease" has also been used to describe
      this syndrome due to the clinical and histopathological similarities between
      Behcet's disease and HSS. Indeed, pulmonary involvement can be indistinguishable
      between these two conditions of unknown pathophysiology. We describe an HSS
      patient who presented with a recurrent pulmonary artery aneurysm, review the
      clinical and pathological manifestations of HSS, discuss its similarities to
      Behcet's disease, and finally make the argument that HSS is in fact Behcet's
      disease.

PMID- 15515790
TI  - Protracted febrile myalgia of familial Mediterranean fever.
AB  - Protracted febrile myalgia (PFM) includes severe myalgia of the upper and lower
      extermities accompanied by fever lasting up to 6 weeks, an elevated erythrocyte
      sedimentation rate and leucucytosis. We report a 13-year-old girl with PFM, and
      discuss the magnetic resonance imaging findings of the involved calf muscles. To
      our knowledge these are the only images of the pathology in the literature.

PMID- 15515791
TI  - An unusual case of Behcet's syndrome: triggered by typhoid vaccination?
AB  - A case of Behcet's syndrome in a 32-year-old woman occurring shortly after her
      third vaccination against typhoid fever is described. Scleritis and pyoderma
      gangrenosum were unusual manifestations of BS that occurred in this case.
      Treatment benefit was provided by mycophenolate mofetil and etanercept. As
      bacterial antigens have been proposed as potential triggers for the onset of BS,
      it is possible that the syndrome was precipitated by typhoid vaccination in this
      patient.

PMID- 15515792
TI  - Severe outcome of juvenile idiopathic arthritis (JIA) associated with familial
      Mediterranean fever (FMF).
AB  - Juvenile Idiopathic Arthritis (JIA) and Familial Mediterranean Fever (FMF) may
      involve the same population of children and be confused at times. In a cohort of
      350 consecutive FMF patients followed by us, 98 had onset before 10 years of age
      and, of those, JIA was present in 3. All three had the M694 V mutation of the
      MEFV gene and were of North African ancestry. The prognosis of these 3 was
      extremely poor: one developed bilateral knee osteonecrosis with total joint
      replacement, repeated ileal obstruction with small bowel resection, renal failure
      and sterility due to amyloidosis and osteoporotic fractures and died at 42 years
      of age; a second developed deforming erosive arthropathy and underwent bilateral
      total hip replacement; the third developed severe erosive polyarthritis and also
      underwent bilateral hip replacements. Aggressive treatment is indicated when JIA
      and FMF coexist.

PMID- 15515793
TI  - Hypermobility and fibromyalgia frequency in childhood familial Mediterranean
      fever.

PMID- 15515794
TI  - Necrotizing crescentic glomerulonephritis with granulomatous vasculitis in a
      patient with familial Mediterranean fever and renal amyloidosis.

PMID- 15515795
TI  - Behcet's disease: does lack of knowledge result in under-diagnosis?

PMID- 15515796
TI  - Familial Mediterranean fever and Celiac sprue--are they related?

PMID- 15515797
TI  - What is your diagnosis? Cerebrovascular hemorrhage.

PMID- 15515798
TI  - Cheyletiella infestation in the dog: observations on diagnostic methods and
      clinical signs.
AB  - The aims of this study were to evaluate the ability of diagnostic methods to
      detect naturally occurring Cheyletiella infestation in dogs, and to quantify and
      relate the number of mites and eggs present to clinical signs. Privately owned
      dogs with skin problems were eligible for inclusion in the study. Four diagnostic
      tests were performed on each dog in the following order: tape impression, hair
      plucking, skin scraping and vacuum cleaning. Dogs with positive test results for
      Cheyletiella infestation in at least one of the tests under evaluation were
      included in the study (n=27). The severity of pruritus and scaling was graded on
      a four-point fixed scale. The diagnostic findings in vacuum cleaning samples
      provided a semiquantitative measure of the grade of infestation. The vacuum
      cleaning test gave a positive test result in all dogs and was significantly more
      efficient than the other tests evaluated (P<0.01). The number of diagnostic
      findings varied considerably among the different vacuum samples. No significant
      relationship between the number of diagnostic findings and severity of clinical
      signs was detected.

PMID- 15515799
TI  - Treatment of a prolapsed lumbar intervertebral disc in a ferret.
AB  - A seven-month-old, male ferret had acute paraplegia and radiographs showed signs
      of disc prolapse between the second and third lumbar vertebrae (L2/3).
      Hemilaminectomy was performed to decompress the spinal cord. Histological
      examination revealed that the extradural material was consistent with annulus
      fibrosus and the L2/3 articular facets were enlarged as a result of bone
      remodelling. The ferret became ambulatory one month postoperatively. Five months
      postoperatively, the ferret had normal posture with mild proprioceptive deficits
      in the pelvic limbs, and fusion of the L2 and L3 vertebral bodies.

PMID- 15515800
TI  - Umbilico-biliary fistula in a dog.
AB  - This case report describes a previously unreported congenital malformation, an
      umbilico-billary fistula, in a dog. A one-year-old male bulldog was diagnosed
      with umbilico-billary fistula using fistulography. Treatment involving surgical
      removal of the fistula was straightforward and resulted in clinical resolution of
      the problem.

PMID- 15515801
TI  - Acquired amegakaryocytic thrombocytopenia--four cases and a literature review.
AB  - Acquired amegakaryocytic thrombocytopenla was diagnosed in four dogs. Initial
      platelet counts in all four dogs were less than 50,000 x 10(9)/litre and initial
      bone marrow examinations revealed megakaryocytic hypoplasia with minimal changes
      in the erythroid and myeloid cell lines. Two dogs had evidence of idiopathic
      immune-mediated disease and two dogs had evidence of associated infectious
      disease. One dog had a positive antibody titre to Borrella burgdorferi, and one
      dog had positive titres to both Ehrlichia canis and B. burgdorferi. Treatment
      consisted of prednisone and cyclophosphamide for the dogs with presumptive immune
      mediated disease, and prednisone and tetracycline for the dogs with positive
      antibody titres to the Infectious organisms. Both dogs with evidence of
      associated infectious disease responded to treatment. A postmortem examination
      did not reveal the underlying aetiology in the two dogs with presumptive
      idiopathic immune-mediated disease.

PMID- 15515802
TI  - Glenoid dysplasia and bicipital tenosynovitis in a Maine coon cat.
AB  - This report describes a rare case of bicipital tenosynovitis in a Maine coon cat.
      The cat, a three-and-half-year-old neutered female, presented with chronic
      weightbearing lameness of the left forelimb. Flexion of the left glenohumeral
      joint and extension of the left cubital joint were resented, and palpation of the
      biceps brachii tendon in the bicipital groove elicited pain. A mild incongruity
      of the joint with mild degenerative changes was seen radiographically.
      Glenohumeral joint dysplasia was suspected. Ultrasound examination revealed
      marked thickening of the bicipital tendon and moderate effusion of the left
      bicipital tendon sheath. Positive contrast radiography of the joint confirmed
      dilation of the tendon sheath. A tentative diagnosis of bicipital tenosynovitis
      was made and confirmed on arthrotomy. Surgical removal of osteophytes resulted in
      the cat being free from pain but a mild lameness recurred six months after
      surgery.

PMID- 15515803
TI  - Treatment of shoulder instability caused by medial glenohumeral ligament rupture
      with thermal capsulorrhaphy.
AB  - A three-year-old, male springer spaniel had chronic left forelimb lameness with a
      medial glenohumeral ligament tear and articular cartilage damage diagnosed on
      arthroscopy. The animal failed to respond to conservative therapy of rest and an
      intra-articular injection of methylprednisolone. The use of thermal
      capsulorrhaphy using bipolar radiofrequency bought about a return of joint
      stability and resolution of the lameness.

PMID- 15515804
TI  - Disability discrimination act: new requirements.

PMID- 15515805
TI  - [Croup in children--results of prospective, multicenter observation].
AB  - Croup syndrome is an urgent and frequent reason for hospitalization of children.
      MATERIAL AND METHODS: 632 children with croup syndrome (422 boys and 210 girls
      aged 2 months-17 years) admitted to 15 pediatric departments in Lower Silesia
      were prospectively observed for 12 months (from April 2001 to March 2002). We
      conducted prospective survey of clinical and laboratory data from all study
      centers. RESULTS: Following diagnoses were accepted as the croup syndrome:
      subglottic laryngitis in 482 patients (75.4%), laryngotracheobronchitis in 75
      (11.8%), laryngitis in 50 (7.8%) and epiglottitis in 20 children (3%). The most
      severe course was observed in children with epiglottitis. Four of them required
      airway intervention and had endotracheal intubation. H. influenzae b was cultured
      from blood of one patient. The most cases of epiglottitis occurred in the 3rd
      year of life (45%). CONCLUSIONS: 1. The most common reason of croup was
      subglottic laryngitis. 2. Epiglottitis was rare with serious course of disease;
      frequency was comparable with the frequency seen in European countries before the
      implementation of Hib vaccine. The routine use of Hib vaccine in Poland may
      prevent from children life threatening epiglottis cases.

PMID- 15515806
TI  - [Treatment of croup syndrome in children in Poland: results of the prospective
      multi-center observation].
AB  - The aim of the study was to estimate treatment practice in hospital management of
      croup syndrome (laryngitis subglottica) in children in Poland. MATERIAL AND
      METHODS: During the period of 12 months, we have prospectively observed 482
      children with croup syndrome admitted to 15 pediatric departments in Lower
      Silesia (south-west region of Poland). Data concerning epidemiology, clinical
      course and treatment were collected from uniform observation cards. There were
      326 boys and 156 girls aged between 2 and 174 months in our study. RESULTS: Among
      482 observed children, received glucocorticoids 424 (88%) mainly parenteral, L
      epinephrine--211 (43.8%), mist therapy--241 (50%), antihistamines--308 (63.9%),
      antibiotics--280 (58.1%). Children treated with antibiotics were younger
      (p=0.0316), their temperature, amount of leukocytes and value of C-reactive
      protein was higher when compared with those not treated (p=0.0002; p=0.0081,
      p=0.0172 respectively). CONCLUSIONS: Children in Lower Silesia with croup
      syndrome were treated in agreement with recent standards with glucocorticoids
      and/or epinephrine. There was an excessive usage of antihistamines which have no
      established treatment role. It seems that in many cases antibiotic treatment
      could have been avoided.

PMID- 15515807
TI  - [Clinical and mycological examinations of oral mucosa in cyclosporine A treated
      patients after renal transplantation].
AB  - Cyclosporine A (CsA) is one of the basic and often used immunosuppressive agents.
      It is used to prevent rejection of allogenic transplants and to cure many
      diseases with autoimmunological components. The development of transplantology
      and frequent presence of autoaggressive disorders causes increased use of CsA,
      which intensifies problem of side-effects. Gingival overgrowth, oral mucosa
      pathologies related with bacterial, viral and fungal infections and neoplasma are
      described as most frequent side-effects of cyclosporine A in the oral cavity. The
      aim of this study was to assess the frequency of presence of different types of
      oral mucosa lesions in cyclosporine A-treated patients after renal
      transplantation. Thirty renal transplant recipients aged 11-64 years (including
      13 females and 17 males) with cyclosporine treatment period from 6 months to 10
      years were examined. Pathological changes on the oral mucosa were noted in 18
      patients (60%). The fungal infections were the most often observed pathology
      (46.7% of examined persons). In mycological tests Candida albicans was most often
      isolated. Other species: C. kefyr, C. parapsilosis and C. tropicalis were also
      found. In 4 cases cheilitis angularis was additionally diagnosed. In 16.7% of CsA
      treated patients, pathological changes of epithelium with homogenic leucoplakia
      features were observed. Hypertrophic lesions of oral mucosa in 10% of cases and
      many small erosions of inflamed mucosa of hard palate in 1 case were also noted.
      Our observations show connection between incidence of oral mucosa pathologies and
      immunosuppressive treatment. This suggests that interdisciplinary cooperation is
      necessary for early start of prevention and treatment program.

PMID- 15515808
TI  - [Antibiotic susceptibility analysis of Enterococcus spp. isolated from urine].
AB  - Recently increase of enterococcal infections has been observed. These bacteria,
      mainly Enterococcus faecalis and Enterococcus faecium are members of the normal
      flora of gastrointestinal tract but also are typical opportunistic pathogens.
      Enterococci are characterized by natural resistance to numerous antibiotics
      (among them cephalosporins), and also by easy acquired resistance to antibiotics.
      Infections caused by multiresistant strains are difficult in treatment, chronic,
      recurrent and sometimes fatal are described. Enterococcal infections are caused
      often by E. faecalis, rarely by E. faecium. In the last years other species of
      enterococci have been isolated from different clinical materials (E.
      casseliflavus, E. avium, E. durans, E. gallinarum). The aim of this study was to
      analyze the antibiotics susceptibility of Enterococcus spp. isolated from urine
      of children with urinary tract infection (UTI), hospitalized in the Upper
      Silesian Health Center of Child and Mother or treated ambulatory. Susceptibility
      of the 130 strains of E. faecalis and 41 E. faecium to: penicillin, tetracycline,
      high level of aminoglycoside (gentamycin 120 microg and streptomycin 300 microg),
      glycopeptides (vancomycin and teicoplanin), ciprofloxacin and nitrofurantoin was
      estimated. All isolated strains of E. faecalis (100%) were sensitive to
      glycopeptides (vancomycin and teicoplanin) and to nitrofurantoin, 96% strains
      were sensitive to penicillin, 43% to ciprofloxacin and 28% to tetracycline. All
      strains of E. faecium were sensitive to glycopeptides (vancomycin and
      teicoplanin), 32% strains were sensitive to penicillin, 19% to tetracycline 14%
      to ciprofloxacin and 50% to nitrofurantoin. Twenty two strains of E. faecalis
      (17%) and twelve strains of E. faecium (29%) were demonstrated high level
      resistance to aminoglycosides (HLAR). Among HLAR strains of enterococci, were
      observed strains of high level resistance only to streptomycin, high level
      resistance only to gentamycin and high level resistance to both aminoglycosides.
      The HLAR strains of E. faecalis and E. faecium were also resistant to other
      antibiotics: penicillin, tetracycline and ciprofloxacin. The most frequent cause
      of child urinary tract infection was E. faecalis, with high sensitivity to
      penicillins, glycopeptides and nitrofurantoin. The increased role of E. faecium
      and other strains of enterococci also has been shown. These species demonstrated
      sensitivity to glycopeptides, but resistance to other antibiotics, routinely used
      for treatment of UTI as well as to nitrofurantoin.

PMID- 15515809
TI  - [Surgical strategy and outcome in multiple cerebral aneurysms].
AB  - INTRODUCTION: Multiple aneurysms of the brain are a more dangerous disorder than
      single aneurysms. Most of patients have evidence of aneurysmal rupture, but
      rebleeding remains an additional danger because of co-existing aneurysms. These
      "silent" aneurysms also have to be operated--the risk of following subarachnoid
      haemorrhage (SAH) is about 2% annually. AIM: The purpose of this study was to
      assess of the surgical outcome in multiple aneurysmal SAH in regard to chosen
      risk factors. MATERIAL AND METHOD: Retrospective analysis of 608 patients treated
      within three years (2001-2003) for cerebral aneurysms in the Department of
      Neurosurgery, Jagiellonian University in Krakow, was carried out. 14% patients
      had multiple aneurysms: 72--two aneurysms, 10 patients three aneurysms, and three
      patients four and more. The mean age was 50, with slight predominance of women
      (58%). Most patients were operated on via pterional craniotomy, and posterior
      circulation aneurysms were clipped by means of suboccipital approach. "Silent"
      aneurysms being clipped in the first stage, if were available via the same
      craniotomy, another--in the next stage. We analyzed short-term outcome of
      multiple aneurysms in comparison to the single (literature data). We presented
      the outcome (according to the Glasgow Outcome Scale) with regard to preoperative
      condition, age, location of the most frequent "bleeding" aneurysms (middle
      cerebral artery, anterior communicating artery), and in patients operated on in
      the 1st and 2nd stage. Accuracy of the preoperative detection of "bleeding"
      aneurysm was checked based on CT, MRI, angio-CT, angio-MRI and DSA. RESULTS AND
      CONCLUSIONS: Out of all 85 treated patients, 64 (75.3%) presented very good and
      good condition on discharge. Five (5.9%) were severe disabled, and 16 (18.8%)
      died. Good preoperative condition, age less than 55, and "bleeding" aneurysms of
      the middle cerebral artery (compared with anterior communicating artery) are good
      prognostic factors in surgically treated multiple aneurysms. Outcome in single
      and multiple aneurysms is similar, excluding perioperative losses, which are 5%
      higher in the multiple aneurysms group. In our series in each case of "bleeding"
      aneurysm was correctly detected preoperatively.

PMID- 15515810
TI  - [Surgery of the ruptured distal anterior cerebral artery aneurysms].
AB  - INTRODUCTION: Distal anterior cerebral artery aneurysms (DACAA) are the
      particular group of the aneurysms of anterior circle of Willis. The
      characteristic factors are: different location on the distal anterior cerebral
      artery, specific surgical approach and rare occurrence. AIM: Retrospective
      analysis of the outcome and attempt to find risk factors in DACAA surgical
      treatment were goals of this report. MATERIAL AND METHOD: The authors report a
      series of 49 cases with DACAA who were operated on in the Department of
      Neurosurgery, Jagiellonian University in Krakow, in the period of 16 years. There
      were 29 women (59.2%) and 20 men (40.8%) with a mean age of 49 years. Multiple
      aneurysm were in 12 cases (24.5%), in which ruptured DACAA were always the cause
      of the haemorrhage. We investigated age, sex, Hunt and Hess grade, arterial
      hypertension, timing of operation, coexistence of intracerebral haematoma (ICH),
      intraventricular haemorrhage (IVH), cerebral ischaemia, hydrocephalus, multiple
      aneurysms, intraoperative aneurysmal rupture, use of temporary parent vessel
      clipping, significant brain oedema during surgery, anatomical variability of
      anterior cerebral artery as a potential risk factors. RESULTS: There were 29
      patients (59.2%) in good and very good clinical state and 11 (22.4%) in poor
      clinical state on discharge. Nine (18.4%) patients died. Statistically
      significant factors such as age (p<0.035), arterial hypertension (p<0.0035), Hunt
      and Hess grade (p<0.0073), IVH (p<0.0054), cerebral ischaemia (p<0.036) affected
      the direct outcome of patients. CONCLUSIONS: There are typical risk factors in
      surgically treated DACAA: age, arterial hypertension, clinical status,
      intraventricular haemorrhage, cerebral ischemia. Most of treated cases remain in
      good and very good condition. Haemorrhagic and ischaemic complications were most
      frequent causes of operating losses in DACAA patients.

PMID- 15515811
TI  - [Psychological evaluation in children with a cavum of the septum pellucidum].
AB  - THE AIM OF THE STUDY: Was to determine the influence of the persistent cavum of
      the septum pellucidum (CSP) on the children intellectual development in different
      age groups. THE MATERIAL AND METHODS: There were 53 children with CSP examined
      (3.4% of the hospitalised children), 28 girls and 25 boys aged 2 months-14 years.
      Among them 30 was with normal intellectual development, 14 children with IQ under
      the average and 9 with mental retardation. The control group consists of 30
      children without CSP and with normal intellectual development. The children were
      divided into three groups: aged under 2 years, between 2 and 6 years and between
      7 and 14 years. Using Psyche Cattell, Terman-Merrill and D. Wechsler (WISC-R)
      scales performed the general intellectual assessment. The evaluation of the
      cognitive, motor abilities and lateralization of the motor and visual functions
      in children was done using tests: Bender-Koppitz, Benton, R. Zazzo, M. Stambak,
      H. Spionek and Lingual Abilities Test. The anamnesis was obtained from parents.
      The statistic analyses was performed with chi-square and Fisher tests. RESULTS:
      The percentage of children with IQ under average and with mental retardation in
      the group <2 years was 60%, in 2-6 years 47% and in the group 7-14 years was 35%.
      The study show significantly lower score in the Code test of the D. Wechsler
      scale in children with CSP and normal intellectual development. Older children
      presented also significantly lower scores in manual abilities. A lot of
      intellectual functions were deleted in the majority of the children with CSP and
      the IQ under the average or with mental retardation. CONCLUSION: The CSP in
      children is connected to the deficits of the intellectual functions and that why
      the psychological assessment should be early performed in children with CSP.

PMID- 15515812
TI  - [Assessment of renal arteries in patients suspected of having renovascular
      hypertension: comparison of Doppler sonography with multiphase MR angiography].
AB  - In 40 patients suspected of having renal artery stenosis Doppler ultrasound and
      multiphase magnetic resonance angiography (MRA) was performed. In 18 cases
      digital subtraction angiography, which served as a reference method, was
      performed. Use of multiphase MRA enabled technique, due to short acquisition
      time, acquisition of 3 phases of examination during a single breath-hold.
      Parameters of MR examination: field = 1.5T, TR = 5 ms, TE = 2 ms, number of
      slices = 30-35, slice thickness = 1 mm, field of view = 30 x 45 cm, matrix = 164
      x 512. Visualization of main and accessory renal arteries, as well as presence
      and grade of stenosis was evaluated. In the group of 18 patients with 42 renal
      arteries, 23 stenoses and 8 accessory arteries were detected. Sensitivity and
      specificity of MRA in diagnosis of renal artery stenosis was 87% and 100%, of
      ultrasound 78% and 100%. During MRA examination, 7 accessory renal arteries were
      visualized, comparing to one detected by USG. Comparing to Doppler ultrasound,
      multiphase MRA has higher sensitivity and similar specificity in diagnosis of
      renal artery stenosis. Ultrasonography, contrary to MRA, has low sensitivity in
      diagnosis of accessory renal arteries.

PMID- 15515813
TI  - [The role of prophylactic examinations in detecting thyroid disorders.
      Preliminary results].
AB  - PREFACE: Nonpalpable nodules in the thyroid are frequent and estimated to be
      found in 50% of people above 50 year of age when goiter in adult population is
      found in 4-10%. Thyroid nodules in 5% are of neoplastic character and their
      diligent investigation is necessary with USG, FNA and certain biochemical factors
      evaluation. Screening is an important part of diagnosing thyroid gland. MATERIAL
      AND METHODS: Prophylactic examination donated by Krakow's City Government was
      performed in 140 persons aged 18-71 among whom 93.3% were women. Clinical
      examination, USG, FNA (when it was necessary), and TSH serum level evaluation
      were conducted in these patients. RESULTS: In 42.2% (group I) no abnormalities
      were detected. In 28.5% (group II) USG revealed thyroid nodules when clinical
      examination was negative. In 29.3% (group III) the presence of palpable nodules
      was confirmed by USG. In consecutive groups I-III following factors were
      presented: mean age, frequency of performed FNA's and thyroids volume.
      CONCLUSION: USG is an efficient method in prophylaxis of thyroid disorders.

PMID- 15515814
TI  - [The impact of income and education on medicine consumption in a representative
      sample of Lodz inhabitants between the ages of 18-64 years].
AB  - Evaluation of medicine consumption and factors influencing it's level is an
      important element in estimation of health care system functionality. One of the
      purposes of CINDI Programme (Countrywide Integrated Noncommunicable Diseases
      Intervention Programme) conducted among the insured in Regional Health Authority
      in Lodz was to evaluate medicine consumption and factors influencing it's level.
      The study was conducted according to WHO standards set for CINDI Programme in 27
      countries. The surveys were directed at random samples of the adult population,
      1857 men and women age 18 to 64 were selected. The data were collected with
      questionnaire at the doctor's visit. The study showed that medicine was taken by
      people in the oldest age groups, with higher education and women. Income had no
      effect on medicine consumption level. Medicine consumption in people with
      diagnosed circulatory system disease depended on age. Analgesic drugs are taken
      more often by older people, women and people with higher education. Sedative
      drugs are more often taken by older women, vitamins are more often taken by women
      with higher education. Among women questioned, small proportion is taking
      substitutive hormonal therapy and contraceptives. Women with higher education are
      taking that therapy most often. Medicine consumption was strongly related to poor
      self-rated health, especially among people with diagnosed chronic disease.

PMID- 15515815
TI  - [Conformal radiotherapy for patients with clinical stage T1-T3 prostate cancer].
AB  - PURPOSE: The purpose of the study is the evaluation of the efficacy and morbidity
      of conformal radiotherapy in patients with clinical stage T1-T3 prostate cancer.
      MATERIAL AND METHODS: The study group comprises 71 patients with clinical stage
      T1-T3, N0, M0 prostate cancer, treated with conformal radiotherapy between 1998
      and 2000. The planned target volume included in all patients prostate a margin
      (PTV1). Forty patients (56%) were initially irradiated for the pelvic region
      (PTV2). The mean total radiation dose delivered to prostate was 68 Gy, and to the
      pelvis--44 Gy. Radiation morbidity was scored by the RTOG/EORTC system, and it
      was analysed in relation to the total dose. The 2-year biochemical relapse-free
      survival and 2-year metastatic control rates were compared by clinical T-stage
      and histologic grade. The probability of biochemical relapse and the probability
      of distant metastases were estimated as a function of clinical T-stage,
      histologic grade, the planned target volume (PTV1 vs PTV1+PTV2) and total
      radiation dose. RESULTS: There were no acute > or = grade III bladder toxicity,
      and only 3 patients (4%), who were irradiated for the pelvis had acute grade III
      bowel toxicity. No patient had late grade > or = III toxicity. The actual 2-year
      biochemical relapse-free survival and 2-year metastatic control according to T
      stage were respectively: T1c--89% and 100%, T2a--90% and 100%, T2b--77% and 85%,
      T2c--62% and 83%, T3--58% and 65%, and by histologic grade they were
      respectively: G1--100% and 100%, G2--79% and 96%, G3--36% and 50%. Statistically
      significant relationships were found between the probability of distant
      metastases or biochemical relapse and histologic grade (p<0.00, p=0.005).
      Clinical T-stage had significant influence on the probability of distant
      metastases and borderline influence on the probability of biochemical relapse
      (p=0.004 and p=0.056). In the multivariate analysis, only histologic grade
      remained significant. CONCLUSIONS: Conformal radiotherapy for prostate cancer is
      well tolerated, and it yields satisfactory results which depend on histologic
      grade and clinical T-stage.

PMID- 15515816
TI  - Effect of hormonal replacement therapy on autonomic regulation of the heart.
AB  - BACKGROUND: Increased incidence of cardiovascular diseases frequently reported in
      postmenopausal women may follow disturbed activity of cardiac autonomic nervous
      system (cANS). Our purpose was to evaluate the influence of continuous combined
      hormonal replacement therapy (ccHRT) on cANS reflected by parameters of heart
      rate variability (HRV). METHOD: Thirty four healthy postmenopausal women aged
      56+/-6 years (7+/-4 years after last menorrhoea) were divided into 2 equal groups
      -women receiving ccHRT (serum estradiol--81+/-75 ng/l, FSH--45+/-27 IU/l) and
      control group (serum estradiol--31+/-45 ng/l, FSH--74+/-32 IU/l). The ccHRT women
      have been receiving daily 50 mg of 17beta-estradiol (Oesclim 50, Fournier) in
      transcutaneous depot and 5 mg of oral progesterone (Duphaston, Solway Pharma) for
      recent 1.4+/-0.6 years. All recordings began at 8.00 a.m. and were carried out in
      supine position and resting conditions (room temperature 24 degrees C). The
      protocol applied consisted of 5 min. of resting ECG recording, 5 min. of deep
      breathing (DB) test, 6 min of sham feeding (SF) and 5 min. of ECG recording after
      SF. RESULTS: Analysis of the resting HRV didn't reveal any significant
      differences between the compared groups. In the control group during DB increases
      of mean LF (455+/-500 vs. 1381+/-1540; p<0.001) and LF/HF (1.5+/-1.1 vs. 5.4+/
      4.3; p=0.002) ratio were observed. No influence of SF on HRV was noticed in this
      group. In the ccHRT women significant increases of mean LF (189+/-125 vs. 728+/
      929; p=0.02) and LF/HF ratio (3.1+/-4.8 vs. 9+/-7.3; p=0.002) were observed
      during DB. SF revealed significant increases of mean RR (841+/-92 vs. 918+/-82;
      p<0.001), SDNN (35+/-14 vs. 43+/-20; p=0.02), LF (189+/-125 vs. 372+/-434;
      p=0.03) and HF (150+/-133 vs. 300+/-332; p=0.01). CONCLUSIONS: Our results
      revealed increased reactivity of the HRV parameters to vagal stimulation by DB
      and SF in the postmenopausal women receiving ccHRT that suggests increased
      activity of cANS in the analysed group. Application of ccHRT restores the
      premenopausal reactivity of cANS.

PMID- 15515817
TI  - [Role of human and bacterial heat shock proteins in inflammatory and
      immunological mechanisms of atherosclerosis].
AB  - Atherosclerosis remains the leading cause of morbidity and mortality in many
      countries. Recent studies have demonstrated that the pathogenesis of
      atherosclerosis involves not only lipid deposition, but also the inflammatory
      process. The heat shock proteins (HSPS) are expressed in normal cells but their
      expression is enhanced by a number of different stress factors including heat and
      ischaemia. They play important roles in chaperoning the "folding" of other
      proteins and in protein degradation.

PMID- 15515818
TI  - [Periodontitis and cardiovascular diseases--review of publications].
AB  - Nowadays periodontal diseases are treated as a one of a social diseases. The main
      consequences of them are: premature teeth loss and possibility of inducing,
      aggravating and modifying many systemic disorders, such as endo- and myocarditis,
      glomerulonephritis, iriditis, retinitis, rheumatic polyarthritis. The scientific
      data performed in the last 10 years indicate links between periodontitis and
      atheromatosis, coronary heart disease and acute coronary events, including
      myocardial infarction. In this study reported was the epidemiological dependences
      between periodontal and cardiovascular diseases. There were described hypotheses
      of negative influence of periodontal foci on induction and progression of
      inflammation in coronary vessel walls and destabilisation of atheromatous
      plaques, also was included theory of direct bacterial invasion and cytokine
      theory. There were shown results of studies which proved the presence of genetic
      material of main periodontal bacterial pathogens, such as Porphyromonas
      gingivalis and Prevotella intermedia, in atheromatous plaques in coronary
      arteries. There were noted other potential mechanisms of induction of acute
      coronary events connected with platelet aggregation induced by specific proteins
      secreted by Streptococcus sanguis and the role of Helicobacter pylori infection,
      the bacteria from periodontal pockets that is presently more often isolated.
      Analysing these data it was concluded, that the co-operation between
      cardiologists and dentists, especially the periodontologists, is necessary during
      the treatment of coronary heart disease. Periodontal therapy should be included
      as an additional element of cardiological therapy. Education of patients is also
      very important for prophylaxis of cardiovascular diseases.

PMID- 15515819
TI  - [Goodpasture syndrome--diagnostic problems].
AB  - This article describes a case of a 44-year-old male patient, with history, of
      tuberculosis who was admitted to the hospital with high temperature, coughing,
      haemoptysis, arterial hypertension and end-stage renal failure. In the
      differential diagnosis of haemoptysis we took into account pneumonia,
      exacerbation of tuberculosis, pulmonary neoplasm and Goodpasture syndrome.
      Presence of antibodies against the glomerular basement membrane (GBM) and
      histopathologic examination of biopsy specimen confirmed the diagnosis of
      Goodpasture syndrome. Due to advanced renal failure haemodialysis therapy was
      introduced. Pharmacological treatment, apart from antibiotics, diuretics and
      hypotension drugs, included prednisone and cyclophosphamide. Despite
      immunosuppressive treatment, we did not observe the return of kidney function and
      thus the patient was enrolled for permanent haemodialysis therapy. We observed a
      permanent absence of antibodies to GBM in the circulation. In the course of 6
      years' treatment, the patient's condition is described as very good with no
      recurrence of haemoptysis. On June 30th 2003 renal transplantation was performed.

PMID- 15515820
TI  - [A case of non-seminomatous testis tumor].
AB  - The authors present a case of germ cell tumor with combined histology, because of
      the unheard size of primary mass. Testis tumors in virtue of their localisation
      and simplicity of self-observation in most cases are early diagnosed.
      Unfortunately there are the cases of the patients who because of the shame, hide
      the disease even from the family for a long time.

PMID- 15515821
TI  - [Adenomatoid tumors of the testis and epididymis].
AB  - The authors report 8 adenomatoid tumors treated in the Urology Department of the
      Medical Academy of Warsaw by organ sparing surgery during 1985-2003. Microscopic
      and immuno-histochemic investigations confirmed their benign character and
      histiogenesis. Follow-up of 6 treated patients, over 5-15 years did not reveal
      recurrence of the neoplasm. Two patients were treated this year and are under
      medical observation.

PMID- 15515823
TI  - [Acute renal failure during HELLP syndrome--case report].
AB  - Case report was presented of a 22 year old pregnant patient with diagnosed
      intrauterine fetal death, who developed HELLP syndrome and acute renal failure.
      Immediate hemodialysis treatment was initiated that permitted management of
      pulmonary edema; subsequent plasmapheresis eliminated not only elevated bilirubin
      and toxins liberated to circulation from the dead intrauterine fetus but also
      allowed for patient recovery. The HELLP Syndrome requires careful obstetric
      supervision and if possible treatment in the Intensive Care Unit.

PMID- 15515822
TI  - [Anhydrotic ectodermal dysplasia as cause of recurrent hyperthermia in a 5 month
      old infant].
AB  - The X-linked anhydrotic ectodermal dysplasia is a rare disease in which defects
      in development of ectodermal derivatives are observed. This syndrome is
      clinically characterized by total or partial anodontia, characteristic physionomy
      and absent or reduced sweating. Recurrent fever was a clue to the disease
      diagnosis in 5 month old infant. The diagnosis was confirmed by the mutation of
      EDA exon 9.

PMID- 15515824
TI  - Does increased dietary salt intake worsen asthma?

PMID- 15515825
TI  - DOTS centre at a tertiary care teaching hospital: lessons learned and future
      directions.
AB  - BACKGROUND: In 1993, Government of India started the Revised National
      Tuberculosis Control Programme (RNTCP). A model Directly Observed Therapy, Short
      Course (DOTS) centre was established at the All India Institute of Medical
      Sciences (AIIMS) to (i) identify the challenges and opportunities in establishing
      DOTS centres at tertiary care facilities, (ii) to teach the strategies of RNTCP
      to medical and paramedical staff, and (iii) to undertake relevant operational
      research connected with tuberculosis (TB) treatment and control. In this
      communication, we describe the experience of establishing a DOTS centre at
      India's premier medical institute and discuss the lessons learned. METHODS: Since
      September 2001 through November 2002 AIIMS employees and their dependants
      diagnosed with tuberculosis were enrolled for treatment at AIIMS DOTS centre. One
      hundred sixty-eight patients were diagnosed as suffering from tuberculosis. Of
      these 49 patients were referred out and remaining 119 patients were treated at
      AIIMS DOTS centre. RESULTS: Treatment success was achieved in 80% (20/25) of new
      smear positive cases and the DOTS centre achieved other targets set up by the
      RNTCP. As the results of the pilot study at AIIMS DOTS centre were favourable,
      the facilities of AIIMS DOTS centre were extended to the general public from
      September 2002 onwards. CONCLUSION: Despite tremendous patient load at tertiary
      care facilities, it is possible to achieve targets established by the RNTCP.
      However, additional research needs to be conducted especially relating to drug
      resistance and surrogate markers of failure under RNTCP.

PMID- 15515826
TI  - Intrapleural streptokinase in complicated parapneumonic effusions and empyema.
AB  - BACKGROUND: The management of complicated parapneumonic effusions (CPE) and
      empyema by chest tube drainage usually fails because of thick viscous fluid and
      multiple pleural space loculations. The use of intrapleural fibrinolytic agents
      facilitates pleural drainage and can obviate the need for more invasive surgical
      interventions in these types of effusions. OBJECTIVE: To evaluate the role of
      intrapleural fibrinolytic therapy with streptokinase (STK) as an adjunctive
      therapy in the management of CPE and empyema. MATERIAL AND METHODS: Thirty
      patients of CPE and empyema were considered for intrapleural fibrinolytic therapy
      when the chest tubes/catheter drainage became insignificant (i.e., less than 50
      ml a day) and the tube was adequately positioned and patent. Intrapleural STK was
      administered eight hourly in the dosage of 2,50,000 IU in 50 ml of saline. The
      end points were volume of fluid drained and radiological resolution. RESULTS:
      [corrected] There were 24 (80%) patients with CPE and six (20%) with empyema,
      with a mean age of 35 years. The median of STK doses used were three in 26 (87%)
      cases and two in four (13%) cases. There was significant drainage (mean +/- SD)
      1094 ml +/- 116 and radiological resolution in 26 (87%) cases. The only
      complication observed was transient chest pain in one and fever in two patients.
      CONCLUSION: Intrapleural fibrinolytic therapy with STK is a safe and effective
      adjunctive therapy in the management of CPE and empyema.

PMID- 15515827
TI  - Development of a computer software for easy storage and analysis of fibreoptic
      bronchoscopy data.
AB  - OBJECTIVE: To develop a simple software for management of fibreoptic bronchoscopy
      records. METHODS: After identification of the specific needs at our hospital, a
      software was developed. A graphical interface with structured data entry related
      to patient information and diagnosis, bronchoscopic findings and specimens
      obtained, and their reports were envisaged. After initial construction, the
      software was tested over a four-week period. The software was put to routine use
      after necessary corrections, and validated over the next few months through
      actual data entry. RESULTS: The software has various modules for input and
      modification of data, as well as for generation of reports, and can work both on
      stand-alone personal computers and on networks. With little practice, residents
      soon became adept at entering details correctly and quickly. The slightly
      increased time of data entry into the computer was more than made up by uniform
      and complete report generation. The database component was evaluated by analyzing
      1000 consecutive records entered over a 14-month period, and no discrepancies
      were observed. CONCLUSION: A user-friendly software providing uniform and
      complete data entry regarding fibreoptic bronchoscopic procedures was developed.

PMID- 15515828
TI  - Lung cancer in India.
AB  - BACKGROUND: Lung cancer is one of the commonest malignant neoplasms all over the
      world. It accounts for more cancer deaths than any other cancer. It is
      increasingly being recognized in India. METHODS: We did a systematic review of
      the published studies on epidemiology, diagnosis and treatment of lung cancer in
      India. Literature from other countries was also reviewed. RESULTS: With
      increasing prevalence of smoking, lung cancer has reached epidemic proportions in
      India. It has surpassed the earlier commonest form of cancer, that of oropharynx,
      and now is the commonest malignancy in males in many hospitals. In addition to
      smoking, occupational exposure to carcinogens, indoor air pollution and dietary
      factors have recently been implicated in the causation of lung cancer. Squamous
      cell carcinoma is still the commonest histological type in India in contrast to
      the Western countries, although adenocarcinoma is becoming more common. Molecular
      genetics of lung cancer has opened up new vistas of research in carcinogenesis.
      Various modalities for early detection through screening are being investigated.
      Majority of the patients have locally advanced or disseminated disease at
      presentation and are not candidates for surgery. Chemotherapy applied as an
      adjunct with radiation improves survival and the quality of life. New anticancer
      drugs, which have emerged during the last decade, have shown an improved efficacy
      toxicity ratio. CONCLUSIONS: In view of our large population, the burden of lung
      cancer will be quite enormous in India. Drastic measures aimed at discouraging
      people from smoking must be taken to reduce the morbidity and mortality due to
      lung cancer.

PMID- 15515829
TI  - Scimitar syndrome: imaging by magnetic resonance angiography and Doppler
      echocardiography.
AB  - We report magnetic resonance angiographic demonstration of both an anomalous
      pulmonary venous drainage and an anomalous systemic arterial supply in a patient
      with scimitar syndrome. Contrast-enhanced magnetic resonance angiography provides
      an excellent non-invasive diagnostic tool for demonstrating this complex
      congenital lesion in detail. A two-dimensional and colour Doppler
      echocardiography was also performed to show the anomalous venous drainage and to
      analyse the anomalous flow velocity pattern.

PMID- 15515830
TI  - Adenoid cystic carcinoma of trachea.
AB  - A 20-year-old male, presented with cough, haemoptysis, breathlessness and
      wheezing for the past one month. Contrast enhanced computerised tomographic
      (CECT), scan of chest and fibreoptic bronchoscopy revealed an endotracheal mass
      that on histopathological examination showed adenoid cystic carcinoma of trachea.
      Magnetic resonance imaging (MRI) scan of chest confirmed involvement of adjacent
      prevertebral, para-oesophageal and subcarinal lymph nodes rendering the tumour
      inoperable.

PMID- 15515831
TI  - Unusual cause for miliary lung mottling in a child.
AB  - A 12-year-old boy presented to us with a diagnosis of disseminated tuberculosis
      which was made based on a history of prolonged fever, multiple neck swellings and
      radiological findings of bilateral multiple micronodular opacities. Examination
      showed a diffuse thyroid gland swelling. He was diagnosed to have papillary
      thyroid carcinoma with distant metastases to cervical lymphnode on histopathology
      and to lungs.

PMID- 15515832
TI  - Disseminated spina ventosa.
AB  - Spina Ventosa is a rare condition. A rare case of disseminated tuberculosis of
      bones and skin without primary foci is presented. Gross sclerosis of the short
      bones of hand and leg were noted.

PMID- 15515833
TI  - Tuberculosis and pregnancy.

PMID- 15515835
TI  - [Definitive adoption of the bioethics law].

PMID- 15515837
TI  - ["World" wounds and scars, a congress to standardize practices. Interview by
      Bernadette Fabregas].

PMID- 15515843
TI  - [Evaluation after one year of portable insulin infusion pumps].

PMID- 15515844
TI  - [Complications in the peristomal zone].

PMID- 15515845
TI  - [Rheumatoid arthritis and care].

PMID- 15515846
TI  - [Rheumatoid arthritis and care. A multifactorial disease of genetic origin].

PMID- 15515847
TI  - [New treatments for rheumatoid arthritis].

PMID- 15515849
TI  - [Rheumatoid arthritis and care. A very painful disease].

PMID- 15515848
TI  - [Nurses' role in patient information and education in rheumatoid arthritis].

PMID- 15515850
TI  - [Rheumatoid arthritis and care. You must always have hope].

PMID- 15515851
TI  - [Rheumatoid arthritis and care. Functional rehabilitation, comprehensive
      management with individualized care].

PMID- 15515853
TI  - [Sophrology and rheumatoid arthritis].

PMID- 15515852
TI  - [Rehabilitation and orthoses fitting in the rheumatoid hand and wrist].

PMID- 15515854
TI  - [Rheumatoid arthritis, someday a disease with predictible progression?].

PMID- 15515855
TI  - [6/9 Handicapped children and education].

PMID- 15515856
TI  - [II--Interpersonal care. 7/10 Persons with difficulties in their social
      relations].

PMID- 15515860
TI  - [Time and the elderly person. The fourth dimension].

PMID- 15515861
TI  - [Time and the elderly person. Patience and length of time].

PMID- 15515862
TI  - [Time and the elderly person. Time and rhythms of life].

PMID- 15515863
TI  - [Time and the elderly person. A time so different!].

PMID- 15515864
TI  - [Time and the elderly person. Institutional meal time, what guidelines for our
      elders?].

PMID- 15515865
TI  - [Time and the elderly person. Living in time].

PMID- 15515866
TI  - [Management of uncomfortable symptoms at the end of life].

PMID- 15515867
TI  - [Professional help for family caregivers in Alzheimer's disease].

PMID- 15515868
TI  - [Nosocomial urinary infections in elderly persons].

PMID- 15515869
TI  - [The benefits of therapeutic baths at home].

PMID- 15515870
TI  - [Physical restraint of elderly persons, risk management and respect for the
      person].

PMID- 15515871
TI  - [Proper nursing role for short stay geriatrics].

PMID- 15515872
TI  - [What is malnutrition?].

PMID- 15515873
TI  - [The "intensive" insulin therapy in artificial feeding. Beneficial effects
      through normal blood sugar level or insulin therapy?].

PMID- 15515874
TI  - Hydroxyethyl starch--can the safety problems be ignored?
AB  - Hydroxyethyl starch (HES) has come into widespread use for fluid management of
      acutely ill patients. Certain characteristic complications of HES, notably renal
      impairment, hemorrhage and pruritus, have been well documented with all types of
      HES solutions. The use of HES solutions with lower molecular weight and
      substitution has been claimed to minimize these safety risks. In particular,
      solutions of 200 kDa molecular weight and 0.5 substitution (HES 200/0.5) and of
      130 kDa molecular weight and 0.4 substitution (HES 130/0.4) have been advocated
      for their superior safety profile. A critical appraisal of the available evidence
      does not provide reassurance that these or other HES solutions are risk free.
      Most evidence indicates the equivalence of HES 200/0.5 and HES 130/0.4 with
      respect to effectiveness for volume expansion. Since HES 130/0.4 is newer, its
      safety profile is less well characterized; however, it appears to share the same
      complication risks as those of HES 200/0.5. In randomized clinical trials
      employing sensitive markers, both HES 200/0.5 and HES 130/0.4 have been shown to
      impair renal function. Both coagulopathy and clinical bleeding have been
      documented after administration of either HES 200/0.5 or HES 130/0.4, and the
      magnitude of negative effects on hemostasis has been similar for these two HES
      solutions. Pruritus is a common side effect of all HES solutions, including HES
      200/0.5 and HES 130/0.4, and can occur in diverse clinical settings in some cases
      after only small HES doses. Typically presenting as pruritic crises of delayed
      onset, this complication is often severe, protracted and refractory to treatment.
      An additional risk of HES infusion is the occurrence of potentially life
      threatening anaphylactoid reactions, which are 4.5 times as frequent after HES as
      albumin exposure. Limiting the dose and duration of HES therapy may be helpful in
      lessening the risk of undesired side effects; at present however, reliance on
      particular HES solutions does not appear sufficient to ensure safety.

PMID- 15515875
TI  - Electrical cardioversion resulting in ventricular fibrillation.

PMID- 15515876
TI  - Comparison of different scoring methods for assessing the nutritional status of
      hospitalised patients.
AB  - OBJECTIVE: Despite intense clinical research, no commonly accepted diagnostic
      tool for assessment of nutritional status is yet available. In this study a
      comparison of four different methods for diagnosis of the nutritional status of
      patients admitted to a university hospital in Austria is presented. PATIENTS AND
      METHODS: Clinical data of 640 hospitalised patients were analysed in a
      prospective-descriptive study design. Four recommended methods, the Innsbruck
      nutrition score (INS), the Prideaux nutritional risk assessment (PNRA), the well
      established nutrition risk index (NRI), and the body mass index (BMI) were used
      to analyse nutritional status. RESULTS: The BMI showed 90.2% of the patients
      evaluated to have normal nutritional status, whereas the PNRA identified 48.9%,
      the NRI 40% and the INS 58.6% as well nourished. Patients were variously
      diagnosed with moderate malnutrition: 9% (BMI), 42% (PNRA), 54.8% (NRI) and 30%
      (INS). Severe malnutrition was detected in 0.5% (BMI), 9.1% (PNRA), 5.2% (NRI)
      and 11.4% (INS) of the patients evaluated. Cancer patients had the worst
      nutritional status. CONCLUSION: Malnutrition seems to be a common diagnosis among
      hospitalised patients in Austria. Screening and assessment of nutritional status
      should be integrated into clinical routine. The methods tested scored
      malnutrition at different frequencies. BMI seemed to underestimate the prevalence
      of malnutrition. The PNRA provided some information on clinical outcome, whereas
      the NRI had the best relationship between the degree of malnutrition and length
      of stay. Calculation of the INS may give correct diagnosis of severe
      malnutrition. Further prospective clinical studies are needed to validate the
      scoring systems used in this study and to provide accurate clinical diagnosis of
      malnutrition.

PMID- 15515877
TI  - Metabolic inefficacy of a short-term low-dose insulin regimen in critically ill
      patients: a randomized, placebo-controlled trial.
AB  - OBJECTIVE: Hyperglycemia and protein catabolism frequently occur in critically
      ill patients and both are associated with increased complication rates. These
      metabolic alterations can be improved by insulin administered exogenously. Since
      a wide range of insulin dosages have been used, this randomized, placebo
      controlled, investigator-blinded, clinical study tests the hypothesis that a low
      dose insulin regimen improves hyperglycemia and protein catabolism in critically
      ill medical patients. PATIENTS AND METHODS: The day after their admission to a
      medical intensive care unit, forty consecutive, critically ill medical patients
      were randomized for receiving either a low-dose insulin regimen (i.e. 1 IU/h)
      (treatment group, n = 20) or placebo (control group, n = 20) continuously over 24
      hours. The primary endpoint was the efficacy of the low-dose insulin regimen to
      decrease serum glucose concentrations; the secondary endpoint was its influence
      on protein catabolism. Serum glucose concentrations and protein catabolism, which
      was assessed by the urea nitrogen appearance rate, were determined at baseline
      and at 8 and 24 hours thereafter. Serum insulin concentrations were measured at
      baseline and after 24 hours. RESULTS: After 24 hours the low-dose insulin regimen
      increased serum insulin concentrations compared with baseline (16.8+/-13.3
      microU/ml and 11.5+/-16.9 microU/ml, respectively; p<0.05). Hyperglycemia and the
      urea nitrogen appearance rate did not change within the two groups of patients
      and there was no difference between the groups at the different time points.
      CONCLUSIONS: Administration of the low-dose insulin regimen was safe. However,
      the short-term low-dose insulin regimen was inefficient in influencing mild
      hyperglycemia and protein catabolism in critically ill medical patients.

PMID- 15515878
TI  - Transjugular intrahepatic portosystemic shunt in Vienna--a decade later.
AB  - Implantation of a transjugular intrahepatic portosystemic shunt (TIPS) for
      therapy of portal hypertension has been available in Vienna, Austria, since 1991.
      Ten years of experience with this technique led the Vienna TIPS Study Group to
      retrospectively analyse characteristics and outcome of all patients undergoing
      TIPS in Vienna between 1991 and 2001. Survival and subgroup analyses were
      performed using Mann Whitney U-tests, log-rank tests, Spearman's correlation and
      Kaplan-Meier analyses. A total of 523 patients underwent TIPS; 23 for acute
      variceal bleeding, 350 for prevention of variceal bleeding, and 109 for therapy
      of refractory ascites. Portal hypertension was caused by cirrhosis in 503
      patients; 20 presented with other diseases. 253 patients died within the study
      period, median follow-up was 5.07 years, median survival 4.51 years. The 3-month,
      1-year, 3-year, and 5-year survival rates were 83%, 71%, 57%, and 49%,
      respectively. Etiology of cirrhosis had no effect on survival; patients with TIPS
      for refractory ascites had poorer survival rates than those undergoing TIPS for
      prevention of rebleeding. TIPS is a safe and effective therapy for patients with
      portal hypertension. The first decade of TIPS in Vienna has shown, in line with
      other publications, that good criteria for patient selection, effective post
      interventional management, and close cooperation between internists,
      interventional radiologists and liver-transplant centers are the key for a good
      outcome.

PMID- 15515879
TI  - High seroprevalence of granulocytic ehrlichiosis distinguishes sheep that were
      the source of an alimentary epidemic of tick-borne encephalitis.
AB  - A sheep herd from which contaminated cheese was produced, causing 21 cases of
      alimentary tick-borne encephalitis (TBE) in human beings, was tested
      serologically for the presence of specific antibodies against both the TBE virus
      (TBEV) and Anaplasma phagocytophilum, the cause of tick-borne fever (TBF) in
      ruminants, and compared with three other herds variously exposed to tick bites
      but without any TBE history. Virus-neutralisation (VN) with the TBEV strain Hypr
      and CV-1 cells was used in TBE tests, and indirect immunofluorescence assay (IFA)
      with neutrophils from goats experimentally infected with A. phagocytophilum was
      used for TBF testing. In 13 sheep from the incriminated herd (N =41), VN titres
      ranging from 1/4 to 1/128 traced previous TBE infection and all sheep had
      elevated titres of A. phagocytophilum antibodies ranging from 1/80 to 1/5120 in
      IFA, whereas two other herds (N = 8 and 9) were seronegative for TBEV and had
      significantly lower levels of A. phagocytophilum antibodies, corresponding to a
      lesser challenge from TBF. A control herd (N = 10) that was grazed on tick-free
      meadows in north Norway was completely seronegative. The respective distributions
      of positive titres of A. phagocytophilum and TBEV antibodies in the incriminated
      herd were not mutually random; the animals with higher anti-A. phagocytophilum
      titres tended to have lower anti-TBEV titres and vice versa (Spearman correlation
      coeff. =-0.86, p< or =0.01). The authors hypothesize that the immunosuppressive
      effect of TBF co-infection in sheep could be a contributory cause of TBE-virus
      contamination of milk, an aspect of TBE epidemiology that has not been considered
      thus far.

PMID- 15515880
TI  - Nutritional depletion in relation to mortality in patients with chronic
      respiratory insufficiency treated with long-term oxygen therapy.
AB  - OBJECTIVE: An association between malnutrition, weight loss and mortality has
      been demonstrated in patients with chronic obstructive pulmonary disease (COPD),
      but the prognostic influence of low body-mass index (BMI) and plasma
      concentrations of albumin and cholesterol is less clear in patients with chronic
      respiratory insufficiency treated with domiciliary long-term oxygen therapy
      (LTOT). We therefore analysed the prognostic value of BMI, plasma albumin and
      cholesterol concentrations in patients receiving LTOT. PATIENTS AND METHODS: From
      1996 to 2001, LTOT was initiated in 255 patients. Analysis of the impact of
      nutritional status on survival was confined to a study group of 108 patients in
      whom the main outcomes, i.e. BMI, plasma cholesterol and albumin, were measured.
      Standard laboratory methods were used in the biochemical analyses. Pulmonary
      function was assessed with bodyplethysmography. RESULTS: 63 patients (58.3%)
      survived for two years post-initiation of LTOT and 45 patients (41.7%) did not.
      There were no differences between these two groups in pulmonary function tests
      and arterial blood gases at the start of LTOT. Overall, 10.2% of the study
      population were underweight, defined as BMI <20 kg/m2. Compared with patients who
      survived two years of LTOT, those who did not survive were older (69.3+/-0.9
      versus 64.7+/-1.2 years, p<0.01), had significantly lower BMI (24.5+/-0.7 versus
      26.5+/-0.7 kg/m2, p < 0.05), lower plasma cholesterol (4.61+/-0.19 versus 5.22+/
      0.13 mmol/l, p<0.01) and lower plasma albumin concentrations (41.4+/-0.4 versus
      42.8+/-0.4 g/l, p <0.05). Logistic regression analysis revealed that, in addition
      to age (p < 0.01), both BMI (p < 0.05) and cholesterol (p < 0.05) significantly
      affected the 2-year survival. CONCLUSION: This study suggests that nutritional
      status is closely linked with prognosis in patients with chronic respiratory
      insufficiency treated with domiciliary LTOT: low BMI, low plasma cholesterol and
      low albumin are related to worse 2-year survival in such patients.

PMID- 15515881
TI  - Thrombophilic polymorphisms--factor V Leiden, prothrombin G20210A, and
      methylenetetrahydrofolate reductase C677T mutations--and preterm birth.
AB  - AIM OF THE STUDY: To evaluate the influence of three common thrombophilic
      polymorphisms, factor V Leiden (FV), prothrombin G20210A (PT), and
      methylenetetrahydrofolate reductase (MTHFR) C677T mutations, on preterm birth of
      unknown cause. PATIENTS AND METHODS: A single-centre case-control study of women
      with preterm infants < or =35 weeks of gestation, in whom obvious maternal,
      uterine, and fetal causes responsible for preterm birth were excluded (n = 35).
      The controls were 54 women with term infants hospitalised in the same ward.
      RESULTS: There were no significant differences between the groups of mothers in
      history of fetal loss, venous or familial thrombosis, or previous preterm birth.
      FV was found in 8.6% of the cases, PT in 5.7%, and MTHFR mutation (homozygous) in
      4.8% compared with 5.4% (p=0.292, OR 1.594, CI95% 0.303-8.384), 7.4% (p=0.379, OR
      0.758, CI95% 0.131-4.374), and 4.5% (p = 0.485, OR 1.050, CI95% 0.090-12.276),
      respectively, in the controls. Differences in the three thrombophilic
      polymorphisms in the two groups of infants were also not significant. CONCLUSION:
      We could not demonstrate a distinct association between these thrombophilic
      polymorphisms and preterm birth.

PMID- 15515882
TI  - Successful switch from inhalative iloprost to oral bosentan in portopulmonary
      hypertension associated with liver cirrhosis.
AB  - Portopulmonary hypertension (PPHTN) is a rare complication of liver cirrhosis.
      Prostanoids have been shown to be effective in the treatment of PPHTN and have
      been used as a bridge to orthotopic liver transplantation. However, inhibition of
      platelet aggregation might be a limitation of prostacyclin therapy in patients
      with end-stage liver disease having an increased risk of bleeding from esophageal
      varices. The effect of oral bosentan, a dual endothelin-receptor antagonist in
      the reversal of PPHTN, is still unclear. We report a case of PPHTN (mean
      pulmonary artery pressure [mPAP] of 51 mmHg) that was successfully switched from
      inhalative iloprost to oral bosentan therapy. Hemodynamic and symptomatic
      improvements were maintained after a 12-month long-term treatment with inhalative
      iloprost as well as after single oral bosentan therapy. This is the first
      reported case of a successful switch from therapy with an inhalative prostacyclin
      analogue to oral bosentan in a patient suffering from PPHTN. Thus, oral bosentan
      therapy might be a promising new option for patients suffering from PPHTN.

PMID- 15515883
TI  - [Causality understanding in oncology with special reference to breast carcinoma].

PMID- 15515884
TI  - Hydroxyethyl starch--can the safety problems be ignored?

PMID- 15515885
TI  - Oxaspirodion, a new inhibitor of inducible TNF-alpha expression from the
      Ascomycete chaetomium subspirale. Production, isolation and structure
      elucidation.
AB  - In a search for new inhibitors of the TNF-alpha promoter activity, a new spiro
      compound, designated oxaspirodion, was obtained as a mixture of four isomers from
      fermentations of the ascomycete Chaetomium subspirale. The structure was
      determined by a combination of spectroscopic techniques.

PMID- 15515886
TI  - Laschiatrion, a new antifungal agent from a Favolaschia species (Basidiomycetes)
      active against human pathogens.
AB  - Laschiatrion (1), a new antifungal antibiotic, was isolated from fermentations of
      Favolaschia sp. 87129. (1) exhibits broad in vitro activity against several human
      pathogens while no antibacterial and cytotoxic activities could be detected. The
      structure was elucidated by spectroscopic techniques. As to our knowledge
      laschiatrion possesses a new steroid skeleton.

PMID- 15515887
TI  - Partial activation of a silent angucycline-type gene cluster from a rubromycin
      beta producing Streptomyces sp. PGA64.
AB  - In the course of DNA-fingerprinting our strain collection for antibiotic
      biosynthesis genes, two different type II polyketide synthase (PKS) gene clusters
      were observed from Streptomyces sp. PGA64. Phylogenetic analysis placed these
      together with known rubromycin and angucycline biosynthetic gene clusters. The
      host strain itself has a very clean production profile of secondary metabolites,
      which composes mainly of rubromycin beta under typical fermentation conditions.
      Sequencing of a 16.5 kb fragment from the putative angucycline cluster revealed
      eight genes that were homologous to typical type II PKS genes responsible for
      synthesizing aromatic polyketides. These genes were especially similar to genes
      from known angucycline biosynthetic gene clusters and also synteny to these
      clusters was observed. In addition, three genes were recognized that are needed
      for priming the minimal PKS complex before polyketide synthesis can initiate, but
      which are not normally found to cluster with antibiotic biosynthesis genes. A
      putative repressor gene that was dissimilar to repressor genes found from well
      characterized antibiotic biosynthesis gene clusters was also discovered. Gene
      disruption of the repressor resulted in partial activation of the cluster and
      production of two angucycline metabolites, UWM6 and rabelomycin. The results
      confirm that the DNA-fingerprinting method we have developed can be used to
      correctly detect compounds that are not visible in chemical screens.

PMID- 15515888
TI  - Growth inhibition dependent on reactive oxygen species generated by C9-UK-2A, a
      derivative of the antifungal antibiotic UK-2A, in Saccharomyces cerevisiae.
AB  - UK-2A is a potent antifungal antibiotic and its structure is highly similar to
      that of antimycin A3 (AA). UK-2A and AA inhibit mitochondrial electron transport
      at complex III. C9-UK-2A, which has been prepared to improve the duration of the
      antifungal activity of UK-2A, shows durable fungicidal activities against various
      species of fungi and induces both membrane injury and the generation of cellular
      reactive oxygen species (ROS) against Rhodotorula mucilaginosa IFO 0001 cells. We
      found that C9-UK-2A inhibited the vegetative growth of Saccharomyces cerevisiae
      IFO 0203 cells accompanying cellular ROS generation in Sabouraud dextrose (SD)
      medium, which contained a fermentable carbon source. The ROS generation was
      completely restricted by pretreatment with a lipophilic antioxidant alpha
      tocopherol. In addition, the pretreatment with the antioxidant protected against
      the growth inhibition induced by C9-UK-2A. C9-UK-2A also induced ROS generation
      in isolated mitochondria of the S. cerevisiae cells. The addition of both a
      complex I inhibitor rotenone and a complex II inhibitor thenoyltrifluoroacetone
      reduced ROS generation induced by C9-UK-2A in the whole cells and the isolated
      mitochondria. The addition of the inhibitors of complex III, AA or myxothiazol,
      or of complex IV, KCN, did not reduce ROS generation. These results suggest that
      C9-UK-2A induces ROS generation due to the blockade of electron flow at complex
      III, thereby inhibiting the growth of S. cerevisiae in SD medium.

PMID- 15515889
TI  - In vitro and in vivo antibacterial activities of the tricyclic ketolide TE-802
      and its analogs.
AB  - The in vitro and in vivo antibacterial activities of tricyclic ketolides (TKs: TE
      802, TE-806, TE-935, TE-943) have been compared with those of clarithromycin
      (CAM), azithromycin (AZM) and rokitamycin (RKM). TKs were active against not only
      erythromycin (EM)-susceptible organisms; aerobic gram-positive bacteria, some
      gram-negative bacteria, anaerobic bacteria and Mycoplasma pneumoniae, but also EM
      resistant Staphylococcus aureus (inducible macrolide-resistant strains) as well
      as EM-resistant Streptococcus pneumoniae (efflux-resistant strains). The
      therapeutic efficacies of TKs against systemic infections and respiratory tract
      infection (RTI) caused by gram-positive bacteria in mice are superior to those of
      CAM and AZM. The peak plasma levels (Cmax, p.o.) of TE-802 in mice were equal to
      that of CAM, but the plasma area under the concentration-time curve (AUC(24
      hours)) was 4.7 times that for CAM. The plasma Cmax (p.o.) value for TE-802 in
      monkey was equal to that of CAM, whereas the AUC(8 hours) value was three-fourths
      that of CAM. The pharmacokinetics of TE-802 are similar to those of AZM in mice
      and monkeys, suggesting the potential for once-daily administration in humans.

PMID- 15515890
TI  - Inhibition of PTP1B by metabolites from Micromucor ramannianus var. angulisporus
      CRM000232.

PMID- 15515891
TI  - MPC1001, a new antitumor antibiotic produced by Cladorrhinum sp.

PMID- 15515892
TI  - Inhibition of Streptomyces chromofuscus phospholipase D by antifungal
      lipopeptides from Bacillus subtilis.

PMID- 15515893
TI  - Determination of the absolute configuration of synerazol.

PMID- 15515894
TI  - Isolation, optimization of production and structure-activity relationship studies
      of monocillin I, the cytotoxic constituent of Paraphaeosphaeria quadriseptata.

PMID- 15515895
TI  - [Determination of species belonging to the Lactobacillus genus with the use of
      RAPD-typing].
AB  - The numeric analysis of 14 strains of lactobacilli investigated by 57
      phenotypical characteristics, has resulted in formation of three clusters: group
      L. delbrueckii, L. plantarum and the modular group formed by strains of various
      species. The API-testing, 16S rRNA sequencing and RAPD-typing with primers 5'
      AGCAGCGTGG-3' and LP3-ST 5'-TGGTCCGAGC-3' have been carried out for several
      strains which position in a dendrogram did not correspond to their species
      diagnosis. The obtained data have allowed the reclassification of the strain L.
      delbrueckii subsp. bulgaricus B-1923T as L. plantarum B-1923T, L. agilis B-2603
      as L. fermentum B-2603, L. amylophilus 30/4/(2) as L. plantarum 30/4/(2). Strain
      L. confusus 39T, identified by the phenotypical characteristics and data of API
      testing as L. fermenturm, was reclassified on the basis of the phylogenetic
      analysis and RAPD-typing, as L. pentosus 39T.

PMID- 15515896
TI  - [Characteristics of structure components of Rahnella aquatilis
      lipopolysaccharides].
AB  - LPS have been isolated from 6 strains of Rahnella aquatilis, their separate
      structure components have been obtained: lipid A, O-specific polysaccharide shain
      (OPS) and core oligosaccharide. 3-Oxytetradecanoic (31.7%) and tetradecanoic
      (17.8%) acids are dominating fatty acids of the lipid A. The core oligosaccharide
      of most investigated strains includes galactose and glucose, some of them include
      arabinose and ribose. Glucose, mannose and galactose are dominating
      monosaccharides in the composition of OPS of the strain 33071, fucose and
      galactose--in OPS of the strains 1-95, 2-95, 2-87 and 3-88, mannose in the
      composition of strain 3-95 OPS.

PMID- 15515897
TI  - [Bacteriophage of Bacillus polymyxa BC153-29].
AB  - A virulent bacteriophage has been isolated from culture liquid of the sowing and
      production fermenter in the process of biosynthesis of polymyxin B; the
      bacteriophage lyses a sensitive producer's culture of antibiotic Bacillus
      polymyxa BC153-29. The bacteriophage has been purified by ultracentrifugation in
      the density gradient of cesium chloride, and its morphology has been investigated
      by the election microscopy. The hexagonal phage head is 72 +/- 1.8 nm in
      diameter, with the length and width of the elastic noncontractile appendix--300
      +/- 2.3 and 14.2 +/- 0.5 nm, respectively. The phage was related to Siphoviridae
      (B1) family. The phage inactivation dynamics has been studied using specific
      antiserum, the phage neutralization velocity constant (595 min(-1)) and phage
      adsorption velocity constant on sensitive cells (9.39 x 10(-8) ml/min) have been
      determined. Exogenic origin of the isolated virulent bacteriophage of Bacillus
      polymyxa BC153-29 has been supposed.

PMID- 15515898
TI  - [Some properties of a mutant of Streptomyces globisporus 1912 supersensitive to
      ultraviolet radiation].
AB  - A well-sporulating mutant Spo 1 has been isolated after the action of defective
      phage from the zone of total lysis of Streptomyces globisporus 1912. It has been
      shown, that mutant Spo 1 is supersensitive to the action of ultraviolet radiation
      and has the increased sensitivity to the action of methyl-methane-sulfonate, has
      mutation in the cluster of genes of synthesis of landomycin E and is not
      sensitive to the action of nitrous acid and hydrogen peroxide. Spo 1 also has a
      high level of UV-mutability. After the action of UV on spores 4620 colonies were
      analysed and 17 auxotrophic mutants (0.36%) were selected. Four auxotrophs
      restored their ability to produce landomycin E and a partial block of synthesis
      of the antibiotic was observed in six auxotrophs. Seven of white (lnd E)
      auxotrophs were analysed with the help of a system "secretor-conventer" and it
      has been shown that two mutants do not synthesize daidzeine flavonoide and have
      genotype lnd E dai aux uvs, five of them were capable to synthesize this
      flavonoide and have genotype lnd dai(+) aux uvs. Initial species of S.
      globisporus 1912 has increased sensitivity to lethal action of UV. It is supposed
      that mutant Spo 1 bears two uvs-mutations.

PMID- 15515900
TI  - [TMV-infection localization and development of induced virus resistance in
      Nicotiana sanderae Hort., Datura stramonium L. and Datura metel].
AB  - The localization of virus infection and development of local and systemic induced
      resistance in plants Nicotiana sanderae Hort., Datura stramonium L. and D. metel
      L. infected by TMV have been studied. It was shown that acquired resistance to
      the second infection is induced in hypersensitive plants infected by TMV
      independent of localization mechanism. No definite correlation exists between
      these defense reactions.

PMID- 15515899
TI  - [pSTS4--a new shuttle vector for cyanobacterium Plectonema boryanum CALU 465].
AB  - Three vector constructions--pSTS2, pSTS3 and pSTS4 have been obtained on the
      basis of the standard vector for Escherichia coli pBR 322, cyanobacterial plasmid
      pSM1 and its separate fragments. The structure of pSTS4, carrying the full-size
      plasmid pSM1 (cloned by the restriction site Hpa II), replicated both in the
      cells of E. coli and in the cells-transconjugants of the trichomal cyanobacterium
      Plectonema boryanum. Under these conditions resistance of P. boryanum cells to
      ampicillin increases three orders, and to tetracyclin--50 times. Structural
      integrity of pSTS4 is stably supported in conjugates during seven successive
      passages (time of the experiment) and preserved the transforming capacity in
      respect of the cells of E. coli. It is supposed that pSTS4 is a shuttle-vector
      with two active origins of replication; one of them provides for the replication
      of pSTS4 in E. coli cells, another--in P. boryanum cells.

PMID- 15515901
TI  - [Phytopathogenic viruses and their strains found in the Asian territory of
      Russia].
AB  - More than 50 strains of 42 species representing 16 genera and 7 families of plant
      viruses have been identified in the Asian territory of Russia mainly in the South
      of Far East and Siberia. The viruses were united into the genera according to the
      data on morphology of virions and virus intracellular inclusions, the range of
      host-plants as well as properties of virus in infectious plant sap, physico
      chemical and antigenic properties of capsid proteins. Taking into account
      significant differences of plant virus strains as to biological properties there
      are reasonable proposition to include a strain as an independent taxonomic unit
      into the present day classification of plant viruses.

PMID- 15515902
TI  - [Antibiotic properties of some species of genus Aspergillus MICH].
AB  - Antibiotic activity screening of some species of genus Aspergillus (64 strains)
      to different test-organisms (gram positive, gram negative, phytopathogenic
      bacteria and yeasts) has been carried out. The researched strains A. parvulus, A.
      ochraceus, A. ustus, A. versicolor, A.fumigatus, A. niger, A. deflectus, A.
      clavatus were characterized by a wide spectrum of antibiotic activity; the
      strains A. flavipes, A. sydowii, A. terreus, A. flavus, A. nidulans, A.
      alliaceus, A. fluticulosus were characterized by a narrow spectrum of antibiotic
      activity. Fungistatic activity was shown for some strains of A. ochraceus, A.
      versicolor, A. ustus. The majority of investigated strains were characterized by
      the static action. The species A. parvulus which has not been investigated before
      is distinguished by a wide spectrum of antibiotic activities would be recognized
      most interesting for further investigation.

PMID- 15515903
TI  - [Adhesion of lactic acid bacteria to epithelium of different cavities of the
      human organism].
AB  - During investigation of adhesive properties of lactic acid bacteria it was found
      out that 11 strains adhered to buccal intestinal and vaginal epithelium of human.
      The highest adhesive activity was detected in enterococci (adhesive index 7.75
      14.26), lower one--in streptococci (6.40-9.16). In lactobacilli adhesive
      properties manifested in different ways: Lactobacillus acidophilus strains
      adhered more often to buccal epithelium (2.58-4.60) and rarely--to intestinal and
      vaginal. L. plantarum manifested high adhesive activity (8.03 -9.69) to buccal
      epithelium and lower one--to the rest of epithelium types. Monosaccharide
      composition of glycocalix of 6 strains of lactic acid bacteria was studied to
      understand the adhesion mechanism. It was shown that surface structures of this
      microorganism interact with plant lectins, specific to certain monosaccharides.

PMID- 15515904
TI  - [Effect of radiofrequency of electromagnetic radiation on yeast sensitivity to
      fungicide antibiotics].
AB  - Saccharomyces cerevisiae UCM Y-517, Candida utilis UCM Y-961 and
      Schizosaccharomyces pombe UCM Y-94T have been studied for their sensitivity to
      fungicide antibiotics under the effect of electromagnetic radiation (40.68 MHz,
      15 and 30 W). Yeast sensitivity to nystatin, amphotericin B, klotrimazol,
      itrakonazol, flukonazol as well as the effects arising as a result of the effect
      of radiofrequency radiation are characterized by species specificity. Irradiation
      did not exert statistically reliable effect on S. cerevisiae and S. pombe
      sensitivity to fungicide antibiotics. The increase of resistance of C. utilis to
      antibiotics (growth delay zones were absent in 70-90% of experiments) in the case
      of preliminary irradiation of this strain was stated. Separate preliminary
      irradiation of antibiotics did not result in the change of their antifungal
      activity. The arising effects were noticed to depend on the radiation power.
      Possible reasons of species specificity in sensing electromagnetic radiation are
      considered.

PMID- 15515906
TI  - [Purification of viral drugs for development of diagnostic aids of Teschen
      disease].
AB  - Optimal methods of purification and concentration of teschevirus strain of the
      pigs of the first serotype "Chernigivsky-2372" have been chosen for development
      of the set of Teschen pig discase diagnosticums. It has been established that
      differential centrifugation with following ultracentrifugation in the gradient of
      saccharose density permits to deprive viruses from host cell proteins, empty
      virus capsides and defect virus particles. That is the method fit for
      purification of virus preparations for the solid-phase immunoenzyme analysis.

PMID- 15515905
TI  - [Effect of corrosion inhibitor on adhesion of sulfate-reducing bacteria to steel
      and their production of exopolymer complex].
AB  - It was shown in the laboratory investigations that the cells of sulphate-reducing
      bacteria of both aggressive Desulfovibrio sp. strain Kiev-10 and nonaggressive
      Desulfovibrio desulfuricans strain Kiev-45 strains can produce exopolysaccharides
      (EPS). Plankton (freely floating) cells of sulphate-reducing bacteria produce
      greater quantity of EPS than the cells of the biofilm formed on steel. The
      inducing effect of metal on EPS synthesis by sulphate-reducing bacteria has been
      established. The content of carbohydrates in EPS is higher in the biofilm of
      aggressive strain Desulfovibrio sp. Kiev-10 than in plankton bacteria as well as
      compared with the biofilm of less aggressive strain Desulfovibrio desulfuricans
      Kiev-45. Specific production of EPS of the aggressive strain in the biofilm
      formed on the steel is 3 orders higher than in the plankton cells. It has been
      established that the quantity of cells of sulphate-reducing bacteria adhered to
      steel decreases in the presence of the corrosion inhibitor N-decylpyridinium
      chloride (high-molecular compound of nitrogen-including PAR of the cationic
      type). It is shown that EPS synthesis is blocked in the biofilm formed by
      sulphate-reducing bacteria on steel under the effect of the corrosion inhibitor,
      while EPS production in plankton is stimulated.

PMID- 15515907
TI  - [Classification of mollicutes].
AB  - The paper deals, allowing for the newest achievements in the study of mollicute
      biology, with main principles and characteristics which would to be used in
      classification of these microorganisms. The present classification of mollicutes
      is based on the study of classical features of cells (morphology and
      ultrastructure of cells, morphology of colonies, requirements to nutrition
      components, biochemical and serological properties) and molecular biological
      properties (composition of cell proteins, properties of nucleic acids, and
      especially, ribosomal operons and ribosomal RNA), living conditions, ecological
      niches, etc. The author hopes that the work will help biologists, physicians,
      veterinaries, phytopathologists and other persons interested in the study of
      mollicutes to orient themselves in determining their systematic position.

PMID- 15515908
TI  - Mental health courts and the lesson learned in juvenile court.

PMID- 15515909
TI  - "Reasonable medical certainty": can we meet Daubert standards in insanity cases?

PMID- 15515910
TI  - Assessing competency competently: toward a rational standard for competency-to
      stand-trial assessments.
AB  - This article reports on a survey of forensic psychiatrists and psychologists who
      read two case study vignettes and assessed whether each criminal defendant was
      competent to stand trial, using three differently worded standards of competency:
      one that focused on whether the defendant's thinking was rational, a second that
      focused on whether the defendant's behavior was rational, and a third that did
      not use the word "rational." The objective was to discover whether forensic
      examiners would distinguish among the standards (i.e., find the defendant
      competent under one standard but not under another) or whether they would find
      the defendant competent under all standards or incompetent under all standards.
      In responding to both vignettes, more than three-fourths of all respondents
      either found the defendant competent under all three standards or incompetent
      under all three standards. In addition, in answering one vignette, the
      respondents were divided almost equally in deciding whether the defendant was
      competent to stand trial. These results are analyzed and respondents' comments
      are discussed. The article concludes with specific proposals to improve
      competency-to-stand-trial assessments.

PMID- 15515911
TI  - Commentary: No rational reasons for changing competency-to-stand-trial standard.

PMID- 15515912
TI  - Gender differences in the practice patterns of forensic psychiatry experts.
AB  - In the past 25 years, the number of female forensic psychiatrists has increased
      dramatically. To assess whether there are gender differences in the practice
      patterns of forensic psychiatry experts, members of the American Academy of
      Psychiatry and the Law were surveyed during an annual business meeting. Women in
      the sample were shown to perform fewer categories of evaluation than men. Women
      were less likely than men to do criminal work, civil commitment/involuntary
      medication evaluations, and testamentary capacity evaluations, but there was no
      significant difference in the percentage of those performing some personal
      injury/disability/fitness for duty, custody, sexual harassment, or malpractice
      evaluations. Gender was not a significant factor in determining hourly rate. When
      subjects were asked to comment on whether they thought that gender was a factor
      in the selection of a forensic expert, 80 percent of the women, but only 41
      percent of the men, believed that gender was a consideration.

PMID- 15515913
TI  - Commentary: Do forensic psychiatrists' practice patterns differ based on their
      gender?

PMID- 15515914
TI  - Court responses to Tarasoff statutes.
AB  - Twenty-three states have enacted Tarasoff statutes applicable to psychiatrists.
      Since the first such statute was enacted in California in 1985, a significant
      number of courts in states with this and similar statutes have reviewed Tarasoff
      type claims. This article reviews courts' analyses in 76 such cases. There were
      five basic categories identified, including cases that (I) did not reference the
      statute; (2) referenced the statute, but did not analyze it; (3) referenced the
      statute, analyzed it, and found it created a duty; (4) referenced the statute,
      analyzed it, but found it did not create a duty; and (5) referenced the statute
      in the context of testimonial privilege. Review of these cases revealed that even
      in states that have Tarasoff statutes, clinicians must continue to rely on their
      clinical and ethical judgment, rather than statutory guidance, when considering
      potential protective disclosures or future drafts of protective disclosure
      statutes.

PMID- 15515915
TI  - Commentary: Ethics and law at the bar and on the couch.

PMID- 15515916
TI  - A case of factitious homicidal ideation.
AB  - Homicidal ideation is often fabricated or embellished by psychiatric patients in
      both the emergency room and inpatient settings. Typically, this symptom is
      malingered to achieve short-term hospital admission and temporary relief from
      complications of substance abuse, homelessness, and illicit activities. Very
      rarely, a patient may feign homicidal intent for the primary purpose of remaining
      in the role of patient (factitious disorder). Although factitious disorder with
      psychological symptoms has been described in a variety of circumstances, the
      psychiatric literature lacks any reports of factitious homicidal ideation. This
      is a report on the case of a patient who was civilly committed on numerous
      occasions for protracted periods based solely on his self-professed homicidal
      ideation. The case raises both forensic and clinical questions and reinforces the
      authors' belief that further investigation is needed to develop more
      sophisticated methods of detection, evaluation, and treatment of factitious
      disorder with psychological symptoms.

PMID- 15515917
TI  - Paranoia in African-American men receiving inpatient psychiatric treatment.
AB  - The present study tested a continuum model of paranoid symptom expression in a
      sample of African-American men receiving inpatient treatment in a state
      psychiatric hospital. The continuum measure comprised the scales of Distrust
      (DST), Perceived Hostility of Others (PHO), and False Beliefs and Perceptions
      (FBP) from the Psychiatric Epidemiology Research Interview (PERI), reflecting
      mild to severe paranoia, in the order listed. They were interviewer administered
      with other self-report symptom measures, within three weeks of hospital
      admission, by ethnically matched interviewers. A multivariate model with repeated
      measures for the continuum of paranoia revealed that scores on the PERI paranoia
      scales correlated similarly with scores on the Fenigstein measure of
      interpersonal paranoia, but correlated differentially with the Politic/Law
      subscale of the Cultural Mistrust Inventory, a measure of cultural paranoia.
      Diagnosis and treatment of African-American men for mental health problems in
      correctional and inpatient settings should be sensitive to the distinction
      between clinical and cultural aspects of their experiences.

PMID- 15515918
TI  - Outcomes of assertive community treatment in an NGRI conditional release program.
AB  - This study describes the five-year outcomes of an assertive community treatment
      (ACT) program that monitored 83 acquittees found not guilty by reason of insanity
      (NGRI) placed on conditional release (CR) into the community. Data were collected
      by retrospective review of court reports and a state computer database. Five
      arrests and 60 hospitalizations occurred during the study period; overall, the
      NGRI acquittees were in the community for 83 percent of the time they were
      eligible for conditional release. Multivariate logistic regression analysis
      showed that the duration of conditional release was a positive predictor, and
      paranoid schizophrenia was a negative predictor of hospitalization or arrest. The
      estimated annual rate (EAR) of hospitalization was 14.0 percent, and the arrest
      EAR was 1.4 percent. The ACT model for NGRI acquittees on CR yielded a low arrest
      rate, a moderate hospitalization rate, and good community tenure.

PMID- 15515919
TI  - The American Psychiatric Association's resource document on mental retardation
      and capital sentencing: implementing Atkins v. Virginia.
AB  - State legislatures need guidance in implementing the United States Supreme
      Court's decision in Atkins v. Virginia barring execution of mentally retarded
      offenders. In this Resource Document, the American Psychiatric Association's
      Council on Psychiatry and Law, the component charged with developing policies and
      positions relating to forensic psychiatry, recommends statutory language
      addressing the definition of mental retardation, procedures relating to its
      assessment, and qualifications of testifying experts.

PMID- 15515920
TI  - Commentary: Atkins and clinical practice.

PMID- 15515921
TI  - Commentary: Atkins on a diet--a fit but lean guide for policy-makers.

PMID- 15515922
TI  - Commentary: Old wine in a new bottle.

PMID- 15515923
TI  - Suicide, psychiatric malpractice, and the bell curve.
AB  - The long-recognized "risk factors" of suicide are so fraught with false positives
      and negatives as to be nearly valueless in anticipating and preventing suicide or
      suicide attempts in actual clinical practice. Suicide is no more or less
      foreseeable in the few patients who attempt self-harm than in the many who make
      no such attempts. Finally, it is difficult to distinguish retrospectively the
      quality of the psychiatric care provided to patients who attempt or commit
      suicide from that received by those who do not. Thus, simple chance may be the
      only statistically meaningful risk factor for these tragic treatment outcomes.

PMID- 15515924
TI  - Reflections of a forensic psychiatrist in Washington: politics and policy.

PMID- 15515925
TI  - The whole truth versus the admissible truth.

PMID- 15515926
TI  - [Dynamics of CO2 and CH4 concentration in the mire soil and its impact factors].
AB  - The wetland plays a important role in global carbon cycling in terrestrial
      ecosystem, the greenhouse gas emission in the mire, especially the CO2 and CH4
      level, show distinctly spatial and temporal variation. The product and emission
      of the CO2 and CH4 are related to soil organic carbon (SOC), dissolved organic
      carbon (DOC) and nitrogen content, meanwhile which are affected by the soil
      temperature and hydrological condition. The concentration of CO2 and CH4 are high
      in mire soil in the Sanjiang plain, especial at the root layer (10-35cm). From
      the middle of September to October, the aboveground of plant came into die, but
      the CO2 and CH4 level increase significantly in mire soil, and show significantly
      positive relationship between them. The ecosystem respiration and the soil
      respiration affected the methane emission distinctly, also with the significantly
      positive relationship.

PMID- 15515927
TI  - [Selective reduction of NOx with propene over SnO2/Al2O3 catalyst].
AB  - In the study, a series of SnO2/Al2O3 catalysts with various Sn loading were
      prepared by three different methods (impregnation, co-precipitation and single
      step sol-gel) and their catalytic activities for the selective reduction of NOx
      with propene were investigated. It was found that the catalyst preparation method
      as well as the Sn loading exerted a significant influence on the catalyst
      activity. Catalysts prepared by sol-gel method exhibited the highest activity
      toward NOx reduction and the optimal Sn loading is 5%. 5% SnO2/Al2O3 catalyst
      prepared by sol-gel method was found to be less inhibited by the presence of H20
      than those prepared by other methods. Even in the co-presence of H2O and SO2, it
      still showed the highest activity. The increase of oxygen and propene
      concentration promotes the NOx reduction, respectively.

PMID- 15515928
TI  - [PAHs in airborne particles from Tianjin in winter season].
AB  - Total suspended particles (TSP) samples from 13 stations in Tianjin were
      collected and analyzed for polycyclic aromatic hydrocarbons (PAHs) during 2002
      winter. There was significant difference in total PAH concentration among 13
      samples. TSP samples from the east Economic Development Area and mid-north
      districts had the highest contents of PAHs, while Dagang Oil Field had the lowest
      PAH content. The urban area, south district, and Jixian county had the moderate
      contents of PAHs. Based on the measured concentration of the PAHs, BaP equivalent
      (BaPeq) were derived based on Toxicity Equivalent Factors (TEFs) of the PAHs. The
      total BaPeq values were similar among the samples. The contribution of PAHs with
      five or six rings contributed 90% of the total toxicity, while they accounted for
      only 50% of the total concentration.

PMID- 15515929
TI  - [Selective catalytic reduction of NO on Ag, Co and Cu/Al2O3 in excess oxygen].
AB  - The catalytic activities of alumina-supported Ag, Co and Cu for selective
      reduction of NO with propene as reductant in the presence of excess oxygen were
      investigated. The catalytic performances of single-component catalysts with
      different metal loadings and of samples prepared by various methods such as
      mechanical mixing, one-step impregnation, two-step impregnation, etc. were
      studied. The experimental results showed that the Ag exhibited the highest
      conversion of NO to N2 (approximately 89% with 2% loading, wt.) among single
      component catalysts, the lower was Co, and the lowest was Cu. The sequence of the
      temperature for the maximum conversion was on the order of Cu < Co < Ag. For Ag
      catalysts, the activities between samples of identical loadings prepared by one
      step and two-step impregnation were almost the same. The activities of mixed
      samples were not the simple sum of the single-component catalysts. The mixed Ag
      Co sample possessed the highest activity (80% above). The activities of the
      combinatorial samples declined comparatively to some extent. The activities of
      one-step impregnation samples descended more markedly and the highest conversion
      was only over 30%.

PMID- 15515930
TI  - [Polycyclic aromatic hydrocarbons in plant leaves from Peking University campus
      and nearby in summer season].
AB  - Leaves of 6 plants were collected from two sites on and around Peking University
      campus in summer season of 2003. PAHs in the leaf-wax and tissues were determined
      simultaneously with leaf-wax content, tissue lipid, specific surface, and stomata
      density. The results were compared to investigate the possible sources of PAHs in
      the leaves. For both leaf-wax and tissue samples, levels of PAHs depended on
      plant species and were lower in the samples from campus than those from outside
      of campus in short distance to busy traffic, suggesting a significant influence
      of vehicle emission. The concentrations of PAHs in leaf-wax were 1-2 orders of
      magnitude higher than those in leaf tissues. While the PAH profiles in the leaf
      wax and leaf tissues were similar in general, the relative contents of volatile
      compounds were higher in the tissues than in the wax. Negative correlations were
      identified between PAHs concentration in the leaf-wax and the wax content and
      between the tissue PAH content and stomata density.

PMID- 15515931
TI  - [Preliminary study on HOx photochemical processes in urban atmosphere of
      Guangzhou City].
AB  - Simultaneous measurements of atmospheric hydroxyl radicals (OH) and other
      pollutants in Guangzhou city were carried out in July, 2000. The quantitative
      analysis of HOx reaction cycle during daytime in summer was made. The calculation
      results indicated that the total production rates of OH and HO2 were about 4.5 x
      10(8) OH/(cm3 x s) and 3.8 x 10(8) HO2/(cm3 x s), respectively. The primary OH
      source in urban atmosphere was the photolysis of HONO, while the main OH sinks
      were the reactions of OH with VOCs, HCHO, NO2 and CO. The HOx chemistry in urban
      atmosphere is quite different from that in the remote clean atmosphere.

PMID- 15515932
TI  - [GIS and scenario analysis aid to water pollution control planning of river
      basin].
AB  - The forward and backward algorithms for watershed water pollution control
      planning were summarized in this paper as well as their advantages and shortages.
      The spatial databases of water environmental function region, pollution sources,
      monitoring sections and sewer outlets were built with ARCGIS8.1 as the platform
      in the case study of Ganjiang valley, Jiangxi province. Based on the principles
      of the forward algorithm, four scenarios were designed for the watershed
      pollution control. Under these scenarios, ten sets of planning schemes were
      generated to implement cascade pollution source control. The investment costs of
      sewage treatment for these schemes were estimated by means of a series of cost
      effective functions; with pollution source prediction, the water quality was
      modeled with CSTR model for each planning scheme. The modeled results of
      different planning schemes were visualized through GIS to aid decision-making.
      With the results of investment cost and water quality attainment as decision
      making accords and based on the analysis of the economic endurable capacity for
      water pollution control in Ganjiang river basin, two optimized schemes were
      proposed. The research shows that GIS technology and scenario analysis can
      provide a good guidance to the synthesis, integrity and sustainability aspects
      for river basin water quality planning.

PMID- 15515933
TI  - [Algal inactivation and removal by pulsed magnetic field with varying frequency].
AB  - The paper studied the algal inactivation and removal by pulsed magnetic field
      with varying frequency. The results indicated that algae could be inactivated and
      killed by the magnetic treatment for the circulating water sample. When the
      accumulated resident time reached 6 minutes, the algae became to die with the
      mortality of 94%. If the resident time were 10 minutes, the algal mortality would
      be more than 96%. The treated algae didn't grow within 120 hours, which indicated
      that the "magnetic memory time" can reach 120 hours. For the static sample in
      magnetic field, the inhibition effect became to do the work after 1 hour.
      Different treatment methods brought about different results. It was more
      propitious to inactivate the algae for circulating sample.

PMID- 15515934
TI  - [Catalytic ozonation of trace nitrobenzene in water by iron hydroxide].
AB  - Laboratory produced iron hydroxide was tested for its activity in catalytic
      ozonation of trace nitrobenzene (NB) in water. The catalysis mechanism was
      deduced from the effect of tert-butanol on the reaction and the difference of
      catalytic activity between several typical transition metal oxides. Effects of
      catalyst dose, pH, bicarbonate ion, and times of catalyst reuse on NB removal
      were also examined. The iron hydroxide showed high catalytic activity on
      ozonation of NB with removal rate of NB dissolved in distilled water increased by
      44.8% at reaction time of 20min. The catalysis follows a hydroxyl radical pathway
      and is affected by density of hydroxyl groups on the oxide. An optimal catalyst
      dosage of 100mg/L existed in this experiment. Solution pH near pH of zero charged
      surface of the oxide favored NB removal and bicarbonate concentration of
      2.38mmol/L significantly reduced it. The oxide was used for five times with no
      significant change of its activity and no dissolution was observed.

PMID- 15515935
TI  - [Effect of Fe and Fe2+ on hydrogen production capacity with mixed culture].
AB  - The effects of Fe and Fe2+ concentration in the external environment on hydrogen
      production capacity of ethanol-type fermentative microorganism flora were
      investigated. The optimum range of Fe and Fe2+ concentration enhanced hydrogen
      production were obtained and the characteristic of fermentation types at
      different concentration of Fe and Fe2+ were discussed. It was demonstrated that
      both Fe and Fe2+ were able to enhance the hydrogen production capacity of
      microorganism flora. The maximum hydrogen production yield of 143.7mL x g(-1)
      glucose and the maximum specific hydrogen production rate 21.2mL x (h x g)(-1)
      were obtained at Fe2+ concentration of 200mg x L(-1) and 50mg x L(-1). The
      maximum hydrogen production yield of 156.1mL x g(-1) glucose and the maximum
      specific hydrogen production rate 23.5mL x (h x g)(-1) were obtained at Fe
      concentration of 1000mg x L(-1) and 500mg x L(-1). At the same concentration, the
      enhancement of Fe is better than Fe2+ when the concentration is higher than 50 mg
      x L(-1). A sequential extraction technique was used to represent arbitrary
      divisions between different metal forms of Fe2+ in the mixed culture.

PMID- 15515936
TI  - [Effect of carbon source and nitrate concentration on denitrifying dephosphorus
      removal and variation of ORP].
AB  - Effect of added carbon source and nitrate concentration on the denitrifying
      phosphorus removal by SBR process was systematicaly studied, at the same time the
      variation of oxidation reductiun potential (ORP) was investigated. The results
      showed the phosphate release rate and the denitrifying and dephosphorus uptake
      rate in anoxic phase increased with the high carbon source concentration under
      anaerobic condition (100-300mg/L). However when the carbon source added in
      anaerobic phase was high to 300mg/L, the residual COD inhibited the succeed
      denitrifying dephosphorus uptake. High nitrate concentration (5, 15, 40mg/L) in
      anoxic phase increased the initial denitrifying dephosphorus rate. Once the
      nitrate depletes, phosphate uptake changed to phosphate release. Moreover, the
      time of the turning point occurred later with the higher nitrate addition. ORP
      can be used as a control parameter of phosphorus release, and it can also
      indicate the denitrificaiton react degree during the anoxic phosphorus removal
      but can't be used as control parameter of phosphorus uptake.

PMID- 15515937
TI  - [Enhancing resistance of a conventional activated sludge system against shock
      loading of 2,4-DCP through bioaugmentation with special culture].
AB  - In this study, conventional activated sludge (CAS) systems, which were generally
      used to treat municipal wastewater, were modeled to receive intermittent 2,4
      dichlorophenol (2,4-DCP) shock loadings. The response and stability of the CAS
      system augmented with special culture and the non-bioaugmented control CAS system
      under shock loading conditions were compared. The capability of the bioaugmented
      CAS systems to degrade 2,4-DCP under long-term continuous operation was
      investigated. Results showed that for the CAS systems with 5% and 15% special
      culture addition, their degradation of the target pollutants and resistance
      against shock loadings was enhanced significantly. When 2,4-DCP shock loading
      occurred within the first 30 days after single inoculation, the bioaugmented CAS
      systems maintained high degradation ability to the target pollutants. After 70
      days continuous operation without 2,4-DCP in feed, when the CAS systems
      challenged 2,4-DCP again, the effect of bioaugmentation was greatly reduced and
      the CAS system failed to remove the pollutants and maintain the system stability
      effectively. Therefore, re-supplementation was needed for further treatment of
      2,4-DCP.

PMID- 15515938
TI  - [Performance of treatment wetland systems for surface water quality improvement].
AB  - Intercropped with Phragmites communis and Typha angustifolia, subsurface flow
      constructed wetland systems (CWs) with the surface area of 3 x 20m x 2m were
      established beside Guanting Reservoir, an important source water base of Beijing.
      The treatment performance of the systems with different season were studied, the
      impacts of influent concentration, hydraulic loading rate and water temperature
      on contaminations removal were analyzed. The result showed that the subsurface
      flow CWs had the better decontamination effect to micro-pollution surface water.
      The relationship between the concentrations of CODMn and NH4+ -N in inflow and
      outflow followed the linear equation. The removal rates of total nitrogen (TN)
      and total phosphorus (TP) in the systems were 20%-60% and 30%-45%, respectively.
      The removal rates of contaminations were reduced with the decrease of water
      temperature and the increase of hydraulic loading rate, the removal rates of
      CODMn, N4+ -N and TN showed the positive correlation with their inflow
      concentration, but the removal rate of TP showed the negative correlation with
      its inflow concentration. Operation and management considerations of the
      subsurface flow CWs in winter were investigated in this study.

PMID- 15515939
TI  - [Effects of Mn2+, Mo6+ and Zn2+ on the components change of extracellular
      polymeric substances in activated sludge].
AB  - By specific oxygen uptake rate, (SOUR) measurements of activated sludge with
      different metal ion concentration, the optimal stimulation concentrations of
      Mn2+, Mo6+ and Zn2+ were determined. Then within each metal ion stimulation
      concentration range, extracellular polymeric substances (EPS) were extracted from
      activated sludge and its components (protein, polysaccharide and nucleic acid)
      contents changes were investigated. The results showed that the optimal
      stimulation concentration of each metal ion is 1mg x L(-1). EPS components of
      activated sludge vary obviously with Mn2+ and Zn2+ concentration change but not
      with Mo6+. After storage at low temperature, EPS quantities in activated sludge
      are reduced with polysaccharide reduction is the most.

PMID- 15515940
TI  - [Cultivation of aerobic granular sludge in SBR by seeding anaerobic granular
      sludge].
AB  - Anaerobic granular sludge was inoculated to an aerobic SBR, where CH3COONa was
      used as the carbon source. Observations on the change of granules' shape and
      structure revealed that the granules experienced a shape-keeping and component
      replacing process. The sludge concentration increased at first 4 weeks and then
      decreased to reach a constant of 5g/L at 35d with its SVI of 30 - 40mL/g.
      Granular sludge dominated in the reactor and suspended sludge concentration was
      less than 0.5g/L during the end of the process. Anaerobic granular sludge, in
      which spheral bacteria was the main microorganism, was successfully developed to
      aerobic granular sludge in which filamentous and bacillius bacteria were the
      dominant microorganism.

PMID- 15515941
TI  - [Pretreatment and resource utilization of industrial effluent with benzoic acid].
AB  - Extraction equilibrium of benzoic acid were studied using 20%, 30% and 50%
      tributyl phosphate (TBP) in kerosene, 1-octanol and toluene as the extractants,
      to investigate the efficient method of recovering benzoic and acetic acid in the
      industrial effluent and meeting the requirement of the terminal wastewater
      treatment. The CODCr value in residual phase and the recovery of benzoic acid in
      various extractants were measured. The results showed that the recovery of
      benzoic acid was closed to 100% with 50% TBP/kerosene system, and depended on the
      polarity of extractant for pure solvent system. The recovery with 1-octanol was
      equivalent to the one with 30% TBP. The CODCr value in the residual phase
      depended on the CODCr value from benzoic acid and the solubility of extractant,
      which does not depend on the benzoic acid concentration in the residue phase
      apparently, and shown 50% TBP approximately equal to 30% TBP > 1-octanol > 20%
      TBP > toluene. Meanwhile, the profitable diagram of pretreatment of industrial
      effluent with benzoic acid was suggested, i.e. firstly, extract benzoic acid with
      toluene and return the toluene to the benzoic acid reactor, then, extract acetic
      acid with trialkylphosphine oxide and back-extract the acetic acid with CaO or
      MgO to produce calcium magnesium acetate.

PMID- 15515942
TI  - [Anaerobic biodegradation of nitrophenols with glucose as co-substrate].
AB  - A batch anaerobic test was conducted to examine the biodegradation of 2
      nitrophenol, 4-nitrophenol, 2,4-dinitrophenol and 2,6-dinitrophenol through
      measuring accumulative methane production. The Relative activity values were used
      to judge the inhibition level of nitrophenols on methanogenic bacteria. The test
      conditions was as follow: glucose was used as co-substrate and the temperature is
      35 degrees C. It didn't cause inhibition when concentrations of 2-nitrophenol, 4
      nitrophenol, 2,6-dinitrophenol and 2,4-dinitrophenol were below 24mg/L, 20mg/L,
      12mg/L and 4mg/L respectively. Slight inhibition was caused when concentrations
      of 4-nitrophenol and 2,6-dinitrophenol were 24mg/L and 16mg/L-24mg/L
      respectively. Middle inhibition when concentrations of 2,4-dinitrophenol were
      8mg/L-24mg/L was observed. The inhibition level was 2,4-dinitrophenol > 2,6
      dinitrophenol > 4-nitrophenol > 2-nitrophenol.

PMID- 15515943
TI  - [Pilot test on oil field wastewater biotreatment with thermophilic
      microorganisms].
AB  - The thermophilic microorganisms (50-60 degrees C) are introduced and the contact
      oxidation technology is adopted to treat with the high temperature effluents from
      an oil field in this paper, which solves a problem that the effluents need to be
      cooled in routine biotreatment. The results of the pilot test show that the HRT
      of the biotreatment system adjusted to 8-18h can make CODCr of the effluents
      stable at 175-263mg/L and oil content under 10mg/L on condition that the
      temperature of the influents keeps at 60-65 degrees C, CODCr 300-590mg/L and the
      quality of the oil wastewater is greatly fluctuant. Flocculating process, then,
      can effectively flocculate and precipitate the suspending and residual chroma
      pollutant from the effluents of biotreatment and CODCr in the effluents of
      flocculating process can reduce to 136-229mg/L. And CODCr even reduces to under
      150mg/L after flowing by sand and activated carbon filtration equipments. Under
      the high temperature condition, furthermore, combined stuffing is an ideal
      carrier for the thermophilic microorganisms.

PMID- 15515944
TI  - [Fe(II) enhanced sonochemical degradation of azo dye Acid Red B (ARB)].
AB  - Sonochemical degradation of azo dye Acid Red B (ARB) was studied in this paper.
      The effect of pH and ferrous ion concentrations on the process was investigated.
      The results show that decolorization of ARB proceeds faster in acidic medium. The
      production of H2O2 is proportional to sonication time. The presence of Fe(II),
      which could react with H2O2 to produce *OH, enhances the sonochemical
      decolorizatio and degradation of the dye. The decolorization rates of ARB are
      2.17 and 2.75 times faster, respectively, when Fe(II) concentrations are 1.43
      mg/L and 2.85 mg/L. The UV absorptions at 322 nm and 254 nm also reduce ARB
      dramatically.

PMID- 15515945
TI  - [Synergy effect of dissolved oxygen in photodegradation of propisochlor in
      aqueous solution].
AB  - The synergetic effect of dissolved oxygen (DO) in the photodegradation of
      propisochlor aqueous solution was investigated in the presence of UV. With the
      increase of dissolved oxygen concentration, from 0 to 7.5 mg/L, photodegradation
      of propisochlor was accelerated. After the concentration of 7.5 mg/L, the rate
      and efficiency of photodegradation stopped increasing and began to decrease when
      the concentration became higher. During the photolysis process, dissolved oxygen
      was consumed. It suggested that the oxygen took an active part in the photolysis.
      It was found by analysis that the pohtolysis products under different dissolved
      oxygen concentrations were almost the same, but the production of several
      products was different. Singlet oxygen (1O2) as the resonance intermediate in the
      photolysis systems was confirmed by electron spin resonance spin trapping
      experiments.

PMID- 15515946
TI  - [Microwave assisted UV electrodeless discharge lamp photochemical degradation of
      4-chlorophenol in aquatic solutions].
AB  - A microwave assisted UV electrodeless discharge lamp system (MW/UV) was used for
      photo-degradation of 4CP simulated wastewater. In order to evaluate the
      degradation efficiency of 4CP, UV spectrophotometry and ion chromatography were
      used for determination of 4CP and Cl- respectively. The degradation rate in MW/UV
      system was higher than that in the UV system within 120min, which were 52.40% and
      21.56% respectively. The degradation efficiency was improved by increasing pH
      value of the solution, aerating O2 gas, enhancing light intensity, or adding H2O2
      oxidant. The degradation of 4CP under MW/UV accords with the first order kinetics
      equation.

PMID- 15515947
TI  - [Photocatalytic degradation of ethylene over titania-based photocatalysts].
AB  - The photocatalytic degradation of ethylene over titania-based photocatalysts was
      studied under a non-circulating system using visible or near-UV light. The roles
      of the reaction temperature and the inlet concentration of ethylene and the
      influence of different light source were investigated. Then the efficiency of
      noble metals-doped photocatalyst was compared with that of the bare one. The
      experiment results indicated that when the inlet concentration was in range of 38
      188 mg/m3 the photo-degradation efficiency of the bare photocatalyst dropped
      linearly and very slowly with the increase of inlet concentration of ethylene;
      the degradation efficiency increased as raising the reaction temperature; noble
      metals not only decreased the recombination of electron-hole pairs, but also
      increased the absorption for visible light, leading to the photocatalytic
      efficiency in several-tens times higher in visible light.

PMID- 15515948
TI  - [Photocatalytic functional ceramic and its speciality of photodecomposition].
AB  - Photocatalytic ceramic was prepared by coating photocatalytic membrane on ceramic
      matrix. The photocatalytic behavior of the TiO2 coated ceramic for degradation of
      oleic acid, ethylene, SO2, NOx and sterilization was studied by using XRD,
      chromatogram, in-situ IR and spectrophotometer. The results showed that the
      photocatalytic ceramic prepared by special conditions have the function of
      environmental conservation such as the photodegradating organic contaminants,
      removing inorganic baleful gas and killing bacteria. Degradation ratio of
      ethylene, oleic acid, SO2 and NOx reached 95%-100% respectively for the
      photocatalytic functional ceramic.

PMID- 15515949
TI  - [Effect of ethanol gasoline and unleaded gasoline on exhaust emissions of EFI
      vehicles with TWC].
AB  - The injectors' flow-rate of all test vehicles that each was fixed with a three
      way catalytic converter (TWC) and Electronic Fuel Injection System (EFI) was
      tested including before and after vehicles operated on unleaded and ethanol
      gasoline respectively running for a long time on real road. The three main engine
      out exhaust emissions (HC, CO and NOx) from vehicles operating on different fuels
      were also analyzed by exhaust testing procedure for the whole light-duty vehicle.
      Test results showed that comparing with unleaded gasoline and ethanol gasoline
      has a remarkable effect on decreasing engine-out exhaust emissions of CO and HC
      (both at about ten percent) and the exhaust emissions of CO, HC and NOx from
      vehicles with TWC respectively. When burning with unleaded gasoline the three
      main pollutants from vehicles with TWC have already or nearly reached Europe
      Exhaust First Standard, after changing to ethanol gasoline CO has drastically
      decreased at about thirty percent, while HC and NOx decreased at about eighteen
      and ten percent respectively, at this time which they were all above Europe
      Exhaust Standard First or nearly reached Europe Exhaust Second Standard; ethanol
      gasoline has also other better performance such as a slight cleaning function on
      injectors, a slower deteriorative trend of engine-out CO and HC and a longer
      operating life-span of TWC.

PMID- 15515950
TI  - [Kinetic characteristics of Cd2+ desorption in minerals and soils under simulated
      acid rain].
AB  - The kinetic characteristics of Cd2+ desorption in minerals and soils under
      simulated acid rain were studied by using the flow-stirred method. It showed that
      Cd2+ desorption could be described by first-order kinetics. Percents of
      desorption amounts of Cd2+ calculated were 70%-100% in red soil and goethite, and
      25%-50% in latosols and kaolinite. Parabolic diffusion could describe Cd2+
      desorption kinetics in latosols and not suitable for red soil and goethite and
      kaolinite. Cd2+ desorption, regarded as a heterogeneous diffusion in minerals and
      soils, could be fitted by Elovich equation more than Parabolic diffusion and two
      constant equation. Cd2+ desorption could be divided into fast reaction and slow
      reaction. Except for latosols, fast reaction would be over during 60 min and be
      close to quasi-equilibrium. Adsorption forms of Cd2+ in soil surface could be
      exchangeable and specific. Fast reaction was relative to easily desorbed Cd2+.
      The affinity of edge hydroxyl to Cd2+ would lead to the difference of Cd2+
      desorption rate and amounts. Increase of pH value in effluent indicated H+
      consumption in the processes of Cd2+ desorption.

PMID- 15515951
TI  - [Three patterns of interaction between soil and non-point source P-pollutants in
      agricultural watershed].
AB  - Typical agricultural watershed was selected to study the interactions between
      soil matrix and non-point source P-pollutants in surface runoff under simulative
      conditions. The soil samples were taken in different spatial locations in this
      watershed and were under different degree of human disturbance. The results
      showed that the interactions between different soil matrix and phosphorus could
      be divided into three patterns:retention, release and combination of retention
      and release. Soil of retention pattern has strong adsorption capacity of
      phosphate and will retain phosphorus from polluted runoff. Soil of release
      pattern has significant desorption capacity of phosphate and will release
      phosphorus to the runoff. Soil of retention and release combination pattern will
      retain or release phosphorus according to the phosphate concentration in the
      polluted runoff. These results showed that soil matrix in different spatial
      locations in the agricultural watershed have different ecological functions and
      environmental values under the processing of natural conditions and human
      disturbance. From the view of occurrence of non-point source pollution, these
      soils could become the sink of pollutants as well as the source of pollutants.
      Under some conditions, there has a conversion between sink and source of them.
      These results are valuable for control of non-point source pollution on watershed
      level, identification of key source area of pollutants and improvement of
      efficiency of control measures.

PMID- 15515952
TI  - [Primarily study of alkylphenols in sediment core from Nam Van artificial lake of
      Macao].
AB  - Alkylphenols, nonylphenols (NPs), octylphenol (OP), are known to have estrogenic
      effects. In a sediment core from Nam Van artificial lake of Macao, the
      concentrations of NPs ranged from 2.17 to 5.91 microg/g, with mean value of 3.66
      microg/g during the estuarine sedimentary environment from 1970s-1980s and from
      0.69 to 3.04 microg/g, with mean value of 2.08 microg/g during lagoon sedimentary
      environment in 1990s. The concentrations of OP during the initial stages of
      lagoon environment in the early 1990s were similar to that in the estuarine
      environment, and ranged from 14.33 to 39.11 ng/g. Subsequently, the concentration
      of OP was rapidly decreasing from 6.52 to 2.58 ng/g. Sources of APs in the
      estuarine condition included the urban runoffs from the upstream waters of Pearl
      River Delta and Macao city, but just from Macao in the lagoon condition.
      Consequently, concentration of APs in estuary condition was higher than that in
      lagoon condition. The vertical profile of concentration of APs in the sediment
      core, to some degree, was correlated with the development degree of regional
      economy and the proceeding of wastewater treatment. The results also showed that
      the alkylphenols in overlapping silty layer preferred to transfer downward to
      filling sandy layer.

PMID- 15515953
TI  - [Effect of temperature on decomposition of leachates by WAO/CWAO].
AB  - Catalytic wet air oxidation (CWAO) is a very effective physical chemistry method
      to treat organic wastewater. In this experiment, CWAO is employed to reduce the
      organic compounds in the landfill leachates. Temperature is an important factor
      in treating leachates by CWAO, so the effect of temperature on the reduction
      efficiency and decomposition rate of organic pollutants is investigated
      emphatically and the quantificational relationship is established between the
      decomposition rates and temperatures used in this study. The function of Co/Bi
      catalyst for the reduction of landfill leachates is also discussed. The influence
      of temperature on the degradation of landfill leachates by CWAO is carried out in
      a sealed environment using catalyst. The resulted information shows that the
      reduction rate of total organic carbon (TOC) and chemical oxygen demand (COD)
      increases notably with increase in temperature with or without the catalyst, and
      that the Elovich equation can describe dynamics course of landfill leachates
      degradation well. Rate constant k also increases with increase in temperature and
      the quantificational relationship is established between the rate constant k and
      temperature; the main reason of pH value reducing rapidly at first and later
      rising slowly is that a large amount of organic acid is produced in the early
      period in the reaction and the organic acid is degraded gradually later.
      Degradation of landfill leachates by CWAO can reach better treatment efficiency
      in gentle condition with catalyst Co/Bi in this study. The temperature's
      relatively great impact on the reaction using CWAO is discussed only in the paper
      and the effects of the other reaction conditions such as oxidant and catalyst
      dosage and the concentration of wastewater on degrading efficiency by CWAO are to
      be focused on.

PMID- 15515954
TI  - [Leaching characteristics of heavy metals in MSW fly ash under different
      condition].
AB  - The leaching characteristic of heavy metals in MSW fly ash was studied under
      acidic and alkaline condition. The result showed the leaching characteristic of
      Pb, Zn, Ni, Cr and Hg had similar law, which was these heavy metals could leach
      out under acidic condition and alkaline condition (pH > 12), and the leaching
      amount increased with the leachate density or L/S increasing. For example, under
      acidic and alkaline condition, the leaching amount of Pb increased from 0.457
      mg/kg, 51.142 mg/kg to 104.576 mg/kg, 59.692 mg/kg respectively when L/S
      increased from 20 to 40. Cd and Cu could leaching out only under acidic
      condition. Under acidic condition the leaching rate of Cd, Pb and Zn were higher
      then the others.

PMID- 15515955
TI  - [Toxic-effects of acetochlor, methamidophos and their combination on bacterial
      amount and population richness at molecular levels in agricultural black soils].
AB  - Bacterial amount and population richness in agricultural black soil under the
      stress of acetochlor, methamidophos and their combination were analyzed by CFU
      and 16S rDNA-PCR DGGE. Results showed that both of acetochlor and methamidophos
      had acute toxic effects on the growth of bacteria in agricultural black soil;
      Growth of free-living nitrogen fixing bacteria was inhibited badly by
      methamidophos, but stimulated greatly by acetochlor. The joint inhibitory effects
      of all combinations at different concentration between methamidophos and
      acetochlor on free-living nitrogen fixing bacteria were severer than each of
      their singal factors,which indicate the significant joint toxic effects between
      acetochlor and methamidophos on free-living nitrogen fixing bacteria in tested
      soil. Bacterial population diversity were decreased and the structure were
      changed respectively at different levels according to their concentration and
      combinations. Some bacterial species were diminished, but some others were
      accumulated under the stress of two agrochemicals and their combinations.

PMID- 15515956
TI  - [Correlation of mercury, selenium and other elements in the tissues of fishes
      from the regions at different mercury exposure level].
AB  - The contents of selenium and other elements in fish liver and muscle tissues
      collected from mercury polluted area of Wanshan, Guizhou province of China and
      non-known mercury polluted one of Beijing were determined with instrumental
      neutron activation analysis, and that of mercury was determined with atomic
      fluorescence spectrometry. The correlation among the determined elements,
      especially between mercury and selenium, in the fish tissues were studied. For
      most of the elements significant difference of elemental content was found
      between tissues of liver and muscle, and mostly the content in liver was higher
      than that in muscle. It was interesting to note that the average content of
      mercury in Guizhou fish liver was 25-fold higher than that in Beijing one, and 5
      fold higher in Guizhou fish muscle than that in Beijing one. For most of the
      elements no significant difference on the average content was found between the
      same tissues of the two areas. The molar ratio of Hg/Se increased with the
      increasing of Hg content at the low Hg level, but the alteration trend became
      gently and reached to a higher constant value (about 0.2) at the higher Hg level.
      Only the element of bromine and rubidium was found to have strong linear
      correlation between the two different tissues of liver and muscle. Though certain
      correlation existed among the different elements of fish tissues from the two
      areas, the most significant and the closest one existed between the mercury and
      selenium of muscle tissue of Guizhou fishes. A closer correlation was also found
      between them of liver tissue of Guizhou fishes. As for Beijing fish tissues, the
      correlation of mercury and selenium only existed in liver but no correlation of
      them was found in muscle. Our results confirm the fact that a certain interaction
      exists between mercury and selenium in organisms including fish, and it is more
      evident as the mercury-exposed level is higher. Some significant correlation was
      also observed between other elements, such as potassium and sodium, cesium and
      rubidium, iron and zinc, in fish tissues and it could be well explained by their
      similar chemical and physical properties or their different biological functions.

PMID- 15515957
TI  - [Modification and application of recombinant yeast bioassay for measuring the AhR
      ligand activity].
AB  - A recombinant yeast bioassay, a yeast Saccharomyces cerevisiae, in which the
      human AhR and ARNT complex are coexpressed, is one of the methods to screen the
      active AhR agonist. In this study, the original agonist test was modified. The
      exposure time was reduced from 18 to 8 hours when experiment was under the
      following conditions: (1) the yeast was cultured in 0.2% glucose medium for 24
      hours; (2) chemical exposure was carried in 2% galactose medium in glass tube.
      Finally, the AhR acitivity of hexachlorobenzene and pentachlorobenzene were
      assessed, and their toxicity equivalent factors were found to be 0.018629 and
      0.000294, respectively.

PMID- 15515958
TI  - [Effect of methylmercury on expression of immediate early gene c-jun mRNA in rat
      brain].
AB  - In order to probe into the early prediction molecular index and the signal
      transduction molecular mechanism of methyl mercury chloride (MMC) neurotoxicity,
      the expression of c-jun mRNA in rat brains induced by different concentration MMC
      for different times were observed by using reverse transcription polymerase chain
      reaction (RT-PCR) methods (the control group was physiological saline of 0.9%,
      the concentrations of expose groups were 0.05, 0.5, 5 mg x kg(-1) respectively,
      the sampling times were 20, 60, 240, 1440 min). The result showed the expression
      of c-jun mRNA in rat brains was prior to the accumulation of mercury, and the
      expression of c-jun mRNA in rat brains could early predict the neurotoxicity of
      MMC. IEG (c-jun) participated in the toxicity process of injury by MMC.

PMID- 15515959
TI  - [Properties of Pesudomonas sp. DN-1 in reduction of nitric oxide chelate
      absorption solution].
AB  - Metal chelate absorption is deemed as a promising method of NO removal in FGD
      system, but the difficulty in the regeneration of the absorption solution hinders
      its further development. An original method with microbial reduction is proposed
      in this paper. With the adding of Psudomonas sp. DN-1, which was newly isolated
      from wastewater treatment plant, FeII (EDTA) NO will be reduced to the
      environmentally benign gaseous product of N2, and thus FeII (EDTA) was
      regenerated simultaneously. The effects of the types and amount of carbon source,
      FeII (EDTA) NO concentration, pH, temperature and the biomass inoculation on bio
      reduction efficiency were investigated. The results showed that the microorganism
      exhibited good performance on bio-reduction of FeII (EDTA) NO with the carbon
      sources of glucose. 250 mg x L(-1) glucose was enough for microorganism to reduce
      6.50 mmol x L(-1) FeII (EDTA) NO completely. The rate of FeII (EDTA) NO reduction
      did not increase with adding a larger amount of carbon source. The bio-reduction
      could be achieved efficiently among the temperature range of 40 - 45 degrees C
      and a pH range of 6.9 - 7.2. The bio-reduction rate increased with the increasing
      of biomass inoculation. When FeII (EDTA) NO concentration is less than 11.8 mmol
      x L(-1), the reduction rate increased as the concentration increases, while the
      concentration is over 11.8 mmol x L(-1), the reduction rate keeps constant.

PMID- 15515960
TI  - [Methods of enumeration of bacteria in drinking water].
AB  - Methods of the enumeration of total bacteria and Coliform in drinking water were
      researched in this paper. The differences between heterotrophic plate count and
      direct viable count method were compared. It is concluded that the total number
      of bacteria in R2A medium is one order of quantity higher than the traditional
      plate count agar, and the results of acridine orange direct counts (AODC) is the
      highest. Some different staining methods in direct viable count were also
      compared in this paper, such as nalidixic acid, CTC staining and BacLight
      staining. The proportion of the live bacteria to the dead is about 10%.

PMID- 15515961
TI  - [Study progress on determination of environmental trace toxicants by
      immunosensor].
AB  - Along with the advances in immunoassay and sensing techniques, the immunosensors
      based on specific immunoreaction and immobilized antibody (antigen) as
      recognition element were developed. They can be used for real-time, in-vivo and
      on-the-spot determination of pesticides, industrial organic pollutants, heavy
      metals, biotoxins, etc. with high sensitivity and selectivity. They possess a
      great potential for environmental monitoring. The working mechanism, fabrication
      and classification of immunosensor are briefly introduced in this paper. The
      latest study progress on immobilization methods and sensing techniques of
      immunosensor for determination of trace toxicants is reviewed. The application of
      immunosensor in environmental monitoring and the future development are also
      discussed.

PMID- 15515962
TI  - Digestive phenotypic flexibility in post-metamorphic amphibians: studies on a
      model organism.
AB  - Studies of phenotypic flexibility are central to the understanding of
      evolutionary and comparative physiology. Research conducted on many vertebrate
      species has shown that the digestive system is highly responsive and sensitive to
      environmental cues. However, amphibians, which are a standard and classic model
      organism for the study of many physiological processes, have been poorly
      considered in the study of ecological consequences on digestive flexibility. Here
      we review and analyze the current information on this topic for amphibians. We
      identify three major bodies of empirical evidence: a) seasonal changes in gut
      development, b) lack of dietary modulation of gut attributes in adult
      individuals, c) a relationship between feeding habits and the magnitude of
      digestive performance regulation. Once the natural history characteristics of the
      species under study are taken into account, all the evidence is in full agreement
      with the predictions of digestive theory. We propose that evolutionary and
      comparative physiology could benefit greatly from the study of phenotypic
      flexibility in amphibians.

PMID- 15515963
TI  - Secretory patterns of leptin and luteinizing hormone in food-restricted young
      female sheep.
AB  - Leptin, the product of the ob gene, has been proposed as a metabolic signal that
      regulates the secretion of GnRH/LH. This may be critical during prepubertal
      development to synchronize information about energy stores and the secretion of
      GnRH/LH. This study aimed to assess the effect of food restriction on the
      episodic secretion of leptin and LH in young female sheep. Five 20-week-old
      prepubertal females were fed a low-level diet for 10 weeks to maintain the body
      weight. Control females of the same age received food ad libitum. Blood samples
      were collected at 10-min intervals for six hours at 20, 26, and 30 weeks of age,
      and plasma leptin, LH, insulin and cortisol concentrations were measured. In the
      control group, no changes were found in pulsatile LH secretion characteristics.
      Mean LH concentrations and LH amplitude were lower in the food-restricted group
      than in the control group at 26 and 30 weeks of age. In the control group,
      pulsatile leptin secretion did not change. When compared to control lambs of the
      same age, the food-restricted group showed lower mean plasma leptin
      concentrations, pulse amplitude and plasma insulin levels, after 6 weeks of
      restriction (week 26), although by week 30, plasma leptin concentrations and
      plasma insulin rose to those of the control group. Leptin pulse frequency did not
      change, nor did mean plasma levels of insulin in the control group at any age
      studied. Mean plasma concentration of cortisol did not change within or between
      groups. These data suggest that plasma leptin concentrations may not be
      associated with the onset of puberty under regular feeding and natural
      photoperiod in lambs. Prolonged food restriction, however, induces metabolic
      adaptations that allow an increase of leptin during the final period, probably
      related to the development of some degree of insulin resistance.

PMID- 15515964
TI  - Comparative effect of ion calcium and magnesium in the activation and infection
      of the murine macrophage by Leishmania major.
AB  - Amastigotes of Leishmania major have a great ability to evade destruction in host
      cells. This study investigated the activation in resident, inflammatory
      macrophages and J774 cells in vitro treated with lipopolysaccharide (LPS),
      soluble Leishmania antigen (SLA), calcium ionophore (CaI) and magnesium (Mg2+)
      alone or combined. An increase in nitric oxide (NO) production was observed in
      J774 or inflammatory macrophages treated with LPS alone or in combination with
      SLA and CaI. The same treatments did not affect the NO release by resident
      macrophages. There was no interference in uptake of L. major but CaI decreased
      intracellular proliferation of the parasite. This study demonstrated the
      importance of CaI in decreasing L. major proliferation inside murine macrophages
      while Mg2+ seemed to increase parasite proliferation. These finding may help to
      understand the events involved in host cells' clearance of this pathogen.

PMID- 15515965
TI  - The gonyautoxin 2/3 epimers reduces anal tone when injected in the anal sphincter
      of healthy adults.
AB  - The primary clinical symptom of Paralytic Shellfish Poisoning is acute paralytic
      illness produced by paralyzing toxins. Paralytic shellfish poison is formed by a
      mixture of phycotoxins and their toxicity is due to its reversible binding to a
      receptor site on the voltage-gated sodium channel on excitable cells, thus
      blocking neuronal transmission. We studied the effect of the gonyautoxin 2/3
      epimers by local infiltration in the anal internal sphincter of healthy voluntary
      adults in order to reduce anal tone. The toxin was injected after prior clinical
      evaluation, anoscopy and anorectal manometry. Post injection clinical
      examination, electromyography and anorectal manometry were performed. Resting and
      voluntary contraction pressures were measured and the anorectal inhibitory and
      anocortical reflexes were tested by manometry. Blood and urine samples were
      obtained from each participant, and hemogram, basic metabolic panel, and
      urinalysis were done both before and one week after the injection. This study
      shows, for the first time, that gonyautoxin 2/3 reduces the anal tone by relaxing
      the anal sphincters in 100 % of the participants. Manometric recordings showed a
      significant decrease in anal maximal voluntary contraction pressure after the
      toxin injection, dropping to 55.2+/-6.2 % and 47.0+/-6.8% (Mean Value+/-Std.Dev.)
      of the baseline values at 2 minutes and at 24 hours respectively after the
      injection. Post-injection electromyography showed that activity of the muscle was
      abolished. We conclude that local administration of gonyautoxin 2/3 to the anal
      sphincter produces immediate relaxation and a statistically significant decrease
      in the anal tone (p <0.001).

PMID- 15515966
TI  - Toxic cyanobacteria strains isolated from blooms in the Guadiana river
      (southwestern Spain).
AB  - This paper describes the occurrence of toxic cyanobacteria along the Guadiana
      River over its course between Merida and Badajoz (Extremadura, Spain). Water
      sampling for phytoplankton quantification and toxin analysis was carried out
      regularly between 1999 and 2001 in six different locations, including two
      shallow, slow-flowing river sites, two streamed river sites and two drinking
      water reservoirs. The cyanobacterial community differed significantly between
      these locations, especially during the summer. The predominant genera were
      Microcystis, Oscillatoria, Aphanizomenon and Anabaena. Using an ELISA assay the
      total microcystin contents of natural water samples from the most eutrophic
      locations ranged from 0.10 - 21.86 microg mcyst-LR equivalent x L(-1) in
      Valdelacalzada and 0.10-11.3 microg mcyst-LR equivalent x L(-1) in Vitonogales,
      and a seasonal variation of toxin content was observed. The amount of
      microcystins produced by each strain was determined by ELISA assay and the
      detection and identification of microcystin variants of three toxic strains of
      Microcystis aeruginosa was performed by high performance liquid chromatography
      (HPLC). The analysis of microcystins of the cultured strains revealed that toxin
      production was variable among different strains of M. aeruginosa isolated either
      from different blooms or from the same bloom.

PMID- 15515967
TI  - Role of reactive oxygen species in bradykinin-induced proliferation of vascular
      smooth muscle cells.
AB  - In addition to the induction of cell proliferation and migration, bradykinin (BK)
      can increase c-fos mRNA expression, activate ERK 1/2 and generate reactive oxygen
      species (ROS) in vascular smooth muscle cells (VSMC). It is not known, however,
      whether BK can induce cellular proliferation and extracellular matrix production
      via redox-sensitive signaling pathways. We investigated the role(s) of ROS in
      proliferation, migration and collagen synthesis induced by BK in VSMC derived
      from Sprague Dawley rat aorta. BK (10 nM) increased VSMC proliferation by 30%
      (n=5); this proliferation was inhibited by the antioxidants N-acetylcysteine (20
      mM) and alpha-lipoic acid (LA, 250 mM). In addition, BK induced an increase in
      cell migration and in collagen levels that were blocked by LA. ROS production
      induced by BK (n=10) was significantly inhibited by bisindolylmaleimide (4microM)
      and by PD98059 (40microM). These results suggest that: 1) ROS participate in the
      mechanism(s) used by bradykinin to induce cellular proliferation; 2) bradykinin
      induces ROS generation through a pathway that involves the kinases PKC and MEK;
      and 3) ROS participate in the pathways mediating cell migration and the
      production of collagen as a response to treatment with bradykinin. To our
      knowledge, this is the first report describing mechanisms to explain the
      participation of ROS in the cellular proliferation and extracellular matrix
      pathway regulated by BK.

PMID- 15515968
TI  - Wavelet and Fourier analysis of ventricular and main arteries pulsations in
      anesthetized dogs.
AB  - The purpose of this study was to characterize time-frequency behavior using the
      Continuous Wavelet Transform (CWT) and Fast Fourier Transform (FFT) to analyze
      ventricular and arterial pressure signals from anesthetized mongrel dogs. Both
      ventricular and arterial pressure pulsations were recorded using catheter-tip
      manometers and the CWT was applied to these signals to obtain module
      coefficients, associated contours, and the 3-D representation of these modules.
      FFT was applied to obtain the Fourier spectrum. The mathematical analysis of the
      cardiovascular pressure pulsations permitted the identification of the evolution
      of the frequency components for the aortic and pulmonary valve functions as well
      as the intra-ventricular and respiratory influences on the cardiovascular
      dynamics. The CWT is a very sensitive and reliable procedure for determining the
      three-dimensional (time-frequency-amplitude) of the oscillatory phenomena during
      each cardiac cycle, providing more, although complementary, information than the
      spectral analysis obtained with the FFT. Thanks to the FFT, exact values in Hz
      could be found for the different events produced in each cycle, and thus the
      information provided by CWT could be related to the information provided by FFT.
      The combination of both mathematical methodologies permitted identification of
      each component of the analyzed signals. The 3D representation allowed an easy
      comparison of the relative importance of the complex magnitudes in frequency for
      the different components of the pulsatile waves.

PMID- 15515969
TI  - The gene suicide system Ntr/CB1954 causes ablation of differentiated 3T3L1
      adipocytes by apoptosis.
AB  - The feasibility of ablating differentiated adipocytes and the mechanism of cell
      ablation with a suitable prodrug activating system is described. The system is
      based on the use of E. coli nitroreductase (NTR) enzyme that activates certain
      nitro compounds, such as the antitumor drug CB1954, into cytotoxic DNA
      interstrand cross-linking agents. Differentiated preadipocyte cells (3T3L1)
      transfected with an aP2 driven nitroreductase construct were efficiently killed
      after incubation with medium containing the prodrug CB1954, while untransfected
      cells were not affected. It was demonstrated that the mechanism of cell ablation
      is apoptosis and that the system has a bystander effect mediated by a toxic
      metabolite of the prodrug. The described system should provide a good alternative
      approach for gene therapy studies and a new inducible approach to manipulating
      the number of cells in tissues of transgenic animals and the ability to study the
      recovery of the tissue from cell damage or loss.

PMID- 15515970
TI  - Effect of psychostimulants on distinct attentional parameters in attentional
      deficit/hyperactivity disorder.
AB  - Although there is extensive literature about the effects of stimulants on
      sustained attention tasks in attentional deficit/hyperactivity disorder (ADHD),
      little is known about the effect of these drugs on other attentional tasks
      involving different neural systems. In this study we measured the effect of
      stimulants on ADHD children, both in the electroencephalographic (EEG) activity
      during sustained attentional tasks and in psychometric performance during
      selective attentional tasks. These tasks are known to rely on different cortical
      networks. Our results in children medicated with 10 mg of d-amphetamine
      administered 60 min before the study indicate (i) a significant increase in
      amplitude but not latency of the P300 component of the event-related potential
      (ERP) during the sustained attentional task and (ii) a significant improvement in
      the reaction times and correct responses in the selective attentional task. In
      addition to supporting the use of stimulants in children with attentional
      deficit/hyperactivity disorder, these results show a multifocal activity
      improvement of cortical structures linked to dopamine, and interestingly, to
      attention. All these analyses are framed in a wider study of diverse attentional
      functions in this syndrome.

PMID- 15515971
TI  - Molecular analysis of the eighteen most frequent mutations in the BRCA1 gene in
      63 Chilean breast cancer families.
AB  - BRCA1 gene mutations account for nearly all families with multiple cases of both
      early onset breast and/or ovarian cancer and about 30% of hereditary breast
      cancer. Although to date more than 1,237 distinct mutations, polymorphisms, and
      variants have been described, several mutations have been found to be recurrent
      in this gene. We have analyzed 63 Chilean breast/ovarian cancer families for
      eighteen frequent BRCA1 mutations. The analysis of the five exons and two introns
      in which these mutations are located was made using mismatch PCR assay, ASO
      hybridization assay, restriction fragment analysis, allele specific PCR assay and
      direct sequentiation techniques. Two BRCA1 mutations (185delAG and C61G) and one
      variant of unknown significance (E1250K) were found in four of these families.
      Also, a new mutation (4185delCAAG) and one previously described polymorphism
      (E1038G) were found in two other families. The 185delAG was found in a 3.17% of
      the families and the others were present only in one of the families of this
      cohort. Therefore these mutations are not prominent in the Chilean population.
      The variant of unknown significance and the polymorphism detected could represent
      a founder effect of Spanish origin.

PMID- 15515972
TI  - Fine structure of the eggs of blowflies Aldrichina grahami and Chrysomya pacifica
      (Diptera: Calliphoridae).
AB  - We report here the fine structure of the eggs of blowflies Aldrichina grahami
      (Aldrich) and Chrysomya pacifica Kurahashi. For A. grahami, the plastron is wide
      and extends to almost the entire length of the eggs. The plastron near the
      micropyle is truncated. The polygonal patterns of chorionic sculpture bear a
      distinct swollen boundary. Regarding C. pacifica, the plastron is narrow and
      extends to almost the entire length of the eggs. The plastron near the micropyle
      bifurcates to a Y-shape, but the arms of the 'Y' are short. Information presented
      herein allows some distinctive features to differentiate among eggs of blowfly
      species.

PMID- 15515973
TI  - Compounded equine drugs seized from Kentucky pharmacy.

PMID- 15515974
TI  - Legal challenges, now and tomorrow.

PMID- 15515975
TI  - A personal view of euthanasia procedures.

PMID- 15515976
TI  - Thoughts on the electronic microchip debate.

PMID- 15515977
TI  - Views WNV prevention suggestions as outdated.

PMID- 15515978
TI  - More on animal friendly curriculums.

PMID- 15515979
TI  - The veterinarian's role in conservation.

PMID- 15515980
TI  - What is your diagnosis? Retained root fragment of the left mandibular canine
      tooth (tooth No. 304).

PMID- 15515981
TI  - What is your diagnosis? Patent urachus.

PMID- 15515982
TI  - Use of signal-averaged electrocardiography in the evaluation of arrhythmogenic
      right ventricular cardiomyopathy in boxers.
AB  - OBJECTIVE: To assess signal-averaged electrocardiography (SAECG) for evaluation
      of Boxers with arrhythmogenic right ventricular cardiomyopathy (ARVC) and
      identify dogs at risk for sudden death (SD) or death related to congestive heart
      failure (CHF). DESIGN: Prospective study. ANIMALS: 94 Boxers with ARVC and 49
      clinically normal non-Boxers (controls). PROCEDURE: Boxers were screened for
      ARVC, and severity was estimated by use of echocardiography, 24-hour ambulatory
      ECG, and SAECG. Statistical evaluation was performed to identify significant
      differences in SAECG variables relative to clinical outcome, frequency of
      ventricular arrhythmias, and systolic function. Sensitivity, specificity, and
      positive and negative predictive values were evaluated for each SAECG variable
      for occurrence of SD or death related to CHF. Late potentials were also evaluated
      as a predictor of cardiac-related death. RESULTS: Differences were detected in
      SAECG variables on the basis of clinical outcome, systolic function, and
      frequency of ventricular arrhythmias. More severely affected dogs had
      significantly more abnormal SAECG findings. The presence of late potentials,
      defined as 2 abnormal root mean square values (of 4), was associated with high
      sensitivity, specificity, and negative predictive value for cardiac-related SD or
      death secondary to CHF CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that
      SAECG is a useful noninvasive diagnostic test to evaluate dogs affected with ARVC
      and identify individuals at risk for cardiac-related death.

PMID- 15515983
TI  - Effects of meloxicam on severity of lameness and other clinical signs of
      osteoarthritis in dogs.
AB  - OBJECTIVE: To evaluate effects of meloxicam on severity of lameness and other
      clinical signs in dogs with osteoarthritis (OA). DESIGN: Randomized, controlled,
      multicenter clinical trial. ANIMALS: 217 client-owned dogs with clinical and
      radiographic signs of OA. PROCEDURE: Dogs were randomly assigned to be treated
      with meloxicam (n = 105; 0.2 mg/kg [0.09 mg/lb], SC, once on day 1, then 0.1
      mg/kg [0.045 mg/lb], PO, q 24 h, for 13 days) or a placebo (n = 112). A general
      clinical score was assigned by investigators on days 1 (ie, prior to initiation
      of treatment), 8, and 15 on the basis of severity of lameness, extent of weight
      bearing, and severity of signs during palpation of the affected joint. Owners and
      investigators provided overall evaluations on days 8 and 15. RESULTS: Dogs
      treated with meloxicam had significantly greater improvements in general clinical
      scores, compared with baseline scores, on days 8 and 15 than did dogs treated
      with placebo. On days 8 and 15, percentages of dogs treated with meloxicam in
      which owners and investigators considered treatment to be successful were
      significantly higher than percentages of control dogs in which treatment was
      considered to be successful. No abnormalities in hematologic and serum
      biochemical test results were detected. CONCLUSIONS AND CLINICAL RELEVANCE:
      Results suggest that compared with administration of a placebo, administration of
      meloxicam for 14 days significantly improved the clinical condition of dogs with
      OA without causing adverse effects.

PMID- 15515984
TI  - Cervical syringohydromyelia secondary to a brainstem tumor in a dog.
AB  - An 11-year-old male Pekingese was evaluated because of a history of head tilt.
      Neurologic examination revealed a right-sided head tilt, ataxia, scoliosis, and
      proprioceptive deficits. Diagnostic testing included magnetic resonance imaging
      (MRI) of the head and neck. After IV administration of gadopentetate dimeglumine,
      an extra-axial, highly contrast-enhanced mass in the brainstem, cerebellar
      herniation, and syringohydromyelia were detected via MRI. The dog was treated
      with corticosteroids and radiation therapy of the mass for 4 weeks (total dose,
      42.5 Gy). Magnetic resonance imaging was repeated 9 weeks and 6 months after
      radiation therapy; compared with the initial findings, a reduction in the size of
      the brainstem mass was observed in both MRI scans. The third MRI scan also
      revealed a normal cerebellar shape, no evidence of herniation, and resolution of
      syringohydromyelia in the dog at that time. It is recommended that whenever
      syringohydromyelia is observed via MRI, a primary cause (cranial or caudal to the
      affected region) should be sought.

PMID- 15515985
TI  - Appendicular arterial tumor embolization in two cats with pulmonary carcinoma.
AB  - A 13-year-old neutered male Persian cat and an 11-year-old neutered female
      Persian cat were examined because of an acute onset of lameness. In both cats,
      conscious proprioception and reflexes were diminished in the affected limb. In 1
      cat, no blood flow was detected in the left brachial artery with a Doppler
      ultrasonic flow detector, whereas blood flow in the right brachial artery was
      easily documented. In the other cat, the right femoral pulse was not palpable.
      Neither cat had any echocardiographic evidence of cardiac disease. In both cats,
      treatment was primarily supportive. One cat died, and the other was euthanatized.
      At necropsy, lung lobe consolidation was seen. Microscopically, there was
      multifocal infiltration of the lung parenchyma with cuboidal to columnar
      neoplastic epithelial cells. Neoplastic epithelial cells of similar morphology
      were identified in nodular masses in sections of muscle, and intravascular tumor
      emboli were identified obliterating small and large arterioles.
      Immunohistochemical staining of pulmonary and muscular tissue for pan-cytokeratin
      antigen revealed intense cytoplasmic staining of neoplastic cells. Staining for
      factor VIII-related antigen confirmed that clusters of neoplastic cells
      represented intravascular emboli. Clinical signs in the cats were attributed to
      arterial occlusion by tumor emboli.

PMID- 15515986
TI  - Evaluation of risk factors associated with development of postoperative ileus in
      horses.
AB  - OBJECTIVE: To determine factors associated with development of postoperative
      ileus (POI) in horses undergoing surgery for colic. DESIGN: Prospective case
      control study. ANIMALS: 251 horses undergoing colic surgery, of which 47
      developed POI. PROCEDURE: Signalment, history, clinicopathologic data, pre- and
      postoperative treatments, lesions, complications, costs, and outcome were
      recorded for all horses during hospitalization. RESULTS: Variables associated
      with increased odds of POI included small intestinal lesion, high PCV, and
      increased duration of anesthesia. There was modest evidence that pelvic flexure
      enterotomy and intraoperative administration of lidocaine may have reduced the
      odds of developing POI. CONCLUSIONS AND CLINICAL RELEVANCE: Findings during the
      preoperative and intraoperative periods can be used to identify horses at
      increased risk of POI. Reducing surgical and anesthetic duration should decrease
      the incidence of POI.

PMID- 15515987
TI  - Management of hemodynamic changes associated with removal of a large abdominal
      myofibroblastic tumor in a pony.
AB  - A 22-year-old female Welsh-cross pony was evaluated because of intermittent
      colic, signs of depression, pyrexia, anorexia, muscle wasting with abdominal
      distention, and weight gain over the preceding 12 months. A large abdominal mass
      was detected and surgically removed; the hemodynamic alterations and
      complications caused by the dramatic fluid losses and shifts that can occur in
      association with removal of a large abdominal mass required extensive
      postoperative management. Monitoring of clinical and hematologic variables such
      as attitude, heart rate, mucous membrane color, mean arterial blood pressure,
      PCV, and plasma total protein concentration provided useful information for
      successful management of the patient after surgery. On removal, the tumor weighed
      19% of the pony's body weight and was characterized as a myofibroblastic tumor.
      Myofibroblastic tumors should be considered as a differential for large internal
      abdominal masses in horses, and surgical removal may be feasible and life
      extending with appropriate postoperative care.

PMID- 15515988
TI  - Evaluation of an outbreak of West Nile virus infection in horses: 569 cases
      (2002).
AB  - OBJECTIVE: To characterize an outbreak of West Nile virus (WNV) infection in
      horses in North Dakota in 2002, evaluate vaccine effectiveness, and determine
      horse characteristics and clinical signs associated with infection. DESIGN:
      Retrospective study. ANIMALS: 569 horses. PROCEDURE: Data were obtained from
      veterinary laboratory records, and a questionnaire was mailed to veterinarians of
      affected horses. RESULTS: Affected horses were defined as horses with typical
      clinical signs and seroconversion or positive results of virus isolation;
      affected horses were detected in 52 of the 53 counties and concentrated in the
      eastern and northeastern regions of the state. Among affected horses, 27% (n =
      152) were vaccinated against WNV, 54% (309) were not, and 19% (108) had unknown
      vaccination status; 61 % (345) recovered, 22% (126) died, and 17% (98) had
      unknown outcome. The odds of death among nonvaccinated horses were 3 and 16 times
      the odds among horses that received only 1 or 2 doses of vaccine and horses that
      were vaccinated according to manufacturer's recommendations, respectively. Horses
      with recumbency, caudal paresis, and age > 5 years had higher odds of death,
      whereas horses with incoordination had lower odds of death, compared with
      affected horses without these characteristics. CONCLUSIONS AND CLINICAL
      RELEVANCE: Vaccination appears to have beneficial effects regarding infection and
      death caused by WNV.

PMID- 15515989
TI  - Evaluation of two rapid assays for detecting Cryptosporidium parvum in calf
      feces.
AB  - OBJECTIVE: To evaluate 2 rapid, patient-side assays for detection of
      Cryptosporidium parvum in feces from neonatal calves with diarrhea. DESIGN:
      Diagnostic test evaluation Sample Population-Fecal samples from 96 neonatal (1 to
      30 days old) calves with diarrhea. PROCEDURE: Results of the rapid assays were
      compared with results of microscopic examination of fecal smears that had been
      stained with diamant fuchsin stain. RESULTS: One of the rapid assays correctly
      identified 56 of 62 (90%) fecal samples positive for C. parvum oocysts and 33 of
      34 (97%) fecal samples negative for oocysts. The other assay correctly identified
      53 of 62 (85%) fecal samples positive for oocysts and 33 of 34 (97%) fecal
      samples negative for oocysts. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest
      that these 2 rapid assays are accurate when used to detect C. parvum in fecal
      samples from neonatal calves with diarrhea.

PMID- 15515990
TI  - Taking stock at 2 years--continuing the journey.

PMID- 15515991
TI  - Crossing the digital divide: evaluating online communication between patients and
      their providers.
AB  - OBJECTIVE: To address provider, payer, and patient concerns about the use of
      online communication in healthcare settings by performing a randomized controlled
      trial of a Web-based patient-provider communication tool in primary care.
      SUBJECTS AND METHODS: Forty-one staff physicians and 91 residents in 4 primary
      care centers were randomized to a Web-based online communication system. Patients
      of intervention physicians were encouraged to communicate via the system about
      health issues, scheduling, prescription renewals, referrals, and billing. Data
      collected included patient Web use, e-mail use, telephone calls, visit
      distribution, and physician and patient attitudes toward and satisfaction with
      communication. RESULTS: One thousand thirty-eight patients sent 2238 messages
      during the 40-week study. Half of the messages were directly related to a
      patient's health; half were administrative. Patient Web use peaked at 8.5 weekly
      messages per 100 scheduled visits. Patient e-mail and telephone volume remained
      similar across groups. Intervention physicians reported more positive attitudes
      toward Web-based communication than control physicians (mean Web benefits scale
      score, 4.0 vs 1.1; P = .008), but there were no between-group differences in
      attitudes toward communication in general. Patients and physicians reported
      differential preferences for the use of online communication based on problem
      complexity and sensitivity. CONCLUSIONS: Web-based messaging was lower than
      expected because of patient-related factors and limitations of the technology.
      Patients, physicians, and staff had positive attitudes toward online
      communication. There was no detectable difference in communication volume between
      study groups, but more sensitive measures of work burden need to be developed and
      evaluated.

PMID- 15515992
TI  - Experiences of patients who were early adopters of electronic communication with
      their physician: satisfaction, benefits, and concerns.
AB  - OBJECTIVE: To explore the experiences of patients who were early adopters of e
      mail communication with their physicians. METHODS: Patients' experiences were
      assessed with an Internetbased survey of 1881 individuals and in-depth telephone
      follow-up interviews with 56 individuals who used e-mail to communicate with
      providers. Two investigators qualitatively coded interview comments
      independently, with differences adjudicated by group consensus. RESULTS: A total
      of 311 (16.5%) of the 1881 individuals reported using electronic mail to
      communicate with their physicians. Compared with the population-based Behavioral
      Risk Factor Surveillance Survey, users of e-mail with physicians were twice as
      likely to have a college education, were younger, were less frequently ethnic
      minorities, and more frequently reported fair/poor health. Among the 311 patients
      who used e-mail with their physicians, the most frequent topics were results of
      laboratory testing and prescription renewals. However, many of the 311 users
      (21%) also reported using asynchronous e-mail inappropriately to convey urgent or
      sensitive issues (suicidality, chest pain, etc). Almost all (95%) perceived that
      e-mail was more efficient than the telephone. Important benefits uncovered from
      the interviews were that some patients felt more emboldened to ask questions in e
      mail compared with face-to-face communication with doctors, and liked the ability
      to save the e-mail messages. Users also expressed concerns about privacy.
      CONCLUSION: Patients that use electronic communication with their physicians find
      the communication efficient for disease management. Further patient education
      about inappropriate use of e-mail for urgent issues is needed.

PMID- 15515993
TI  - Consumers' use of the Internet for health insurance.
AB  - OBJECTIVES: We examined consumers' search for information about health insurance
      choices and their use of the Internet for that search and to manage health
      benefits. STUDY DESIGN: We surveyed a random sample of more than 4500 individuals
      aged 21 years and older who were members of a survey research panel during
      December 2001 and January 2002. METHODS: The survey included questions about
      searching for health insurance information in 3 health insurance markets:
      Medicare, individual or nongroup, and employer-sponsored group. We also asked
      questions about use of the Internet to manage health benefits. We tabulated means
      of responses to each question by market and tested for independence across
      demographic groups using the Pearson chi-square test. RESULTS: We identified
      important differences across and within markets in the extent to which people
      look for information about health insurance alternatives and the role of the
      Internet in their search. Although many individuals were unaware of whether their
      employer or health plan provided a website to manage health benefits, those who
      used the sites generally evaluated them favorably. CONCLUSIONS: Our results
      suggest that the Internet is an important source of health insurance information,
      particularly for individuals purchasing coverage individually in the nongroup and
      Medicare markets relative to those obtaining coverage from an employer. In the
      case of Medicare coverage, studies focusing on beneficiaries' use of Internet
      resources may underestimate the Internet's importance by neglecting caregivers
      who use the Internet. Many individuals may be unaware of the valuable resources
      available through employers or health plans.

PMID- 15515994
TI  - The influence of year-end bonuses on colorectal cancer screening.
AB  - OBJECTIVE: To estimate the effect of physician bonus eligibility on colorectal
      cancer (CRC) screening, controlling for patient and primary care physician
      characteristics. STUDY DESIGN: Retrospective study using managed care plan claims
      data from 2000 and 2001. METHODS: Data on 50-year-old commercially insured
      patients in a managed care health plan were linked to enrollment and provider
      files. The data included information on 6749 patients (3058 in 2000 and 3691 in
      2001). Multivariate logistic regression models were used to assess the
      association between CRC screening receipt and physician bonus eligibility.
      RESULTS: From 2000 to 2001, CRC screening use increased from 23.4% to 26.4% (P <
      .01). Results from the multivariate logistic regression analysis revealed that
      the probability that a patient received a CRC screening was approximately 3
      percentage points higher in the bonus year, 2001 (P < .01). CONCLUSIONS: Bonuses
      targeted at individual physicians were associated with increased use of CRC
      screening tests. However, more research is needed to examine the effect of
      performance-based incentives on resource use and the quality of medical care.
      Specifically, there is a need to determine whether explicit financial incentives
      are effective in reducing racial disparities in the quality of patient care. This
      has particular relevance for CRC screening given that black patients are less
      likely to be screened, they have higher CRC incidence and mortality rates
      compared with other racial groups, and screening has been shown to be more cost
      effective in this population.

PMID- 15515995
TI  - Comparison of hospital costs and length of stay associated with general
      internists and hospitalist physicians at a community hospital.
AB  - OBJECTIVE: To compare initial and long-term hospital resource utilization of
      hospitalists and general internists at an urban community hospital. STUDY DESIGN:
      A retrospective cohort analysis. METHODS: Data were collected from 11 750
      admissions associated with 28 diagnosis-related groups for 6 years (October 1,
      1994, to September 30, 2000). Hospital cost, length of stay, mortality, and 30
      day readmission rates of general and hospitalist internists were analyzed for
      comparison. RESULTS: Hospitalists had generally lower utilization compared with
      general internists. Overall, length of stay and hospital cost were 16.1% and 8.3%
      lower, respectively, for hospitalists. Hospital mortality and 30-day readmissions
      were similar for both physician groups. CONCLUSIONS: Hospital resource
      utilization is moderately lower for hospitalists compared with private practicing
      general internists.

PMID- 15515996
TI  - Cost effectiveness of thromboprophylaxis with a low-molecular-weight heparin
      versus unfractionated heparin in acutely ill medical inpatients.
AB  - OBJECTIVE: To compare the cost effectiveness of prophylaxis with a low-molecular
      weight heparin with that of prophylaxis with unfractionated heparin for the
      prevention of venous thromboembolism in acutely ill medical inpatients. STUDY
      DESIGN: Cost-effectiveness analysis based on decision-tree model. PARTICIPANTS
      AND METHODS: A hypothetical cohort of 10 000 patients was assumed to receive
      either (1) prophylaxis with enoxaparin, a low-molecular-weight heparin, 40 mg
      daily; (2) prophylaxis with unfractionated heparin, 5000 IU twice daily; or (3)
      no prophylaxis. We developed a decision-analytic model with parameter estimates
      derived from published clinical trials and other secondary sources. Then, for
      each strategy, we estimated the risks of venous thromboembolism, complications of
      prophylaxis and treatment (heparin-induced thrombocytopenia and bleeding),
      mortality, and costs of prophylaxis and treatment within a 30-day period.
      RESULTS: In a hypothetical cohort of 10 000 inpatients, expected numbers of
      deaths attributable to venous thromboembolism or drug complications related to
      both prophylaxis for and treatment of VTE over a 30-day period were 37 with
      enoxaparin prophylaxis, 53 with unfractionated heparin prophylaxis, and 81 with
      no prophylaxis. In 2001, corresponding expected costs of prevention, diagnosis,
      and management of VTE were $3 502 000 for enoxaparin, $3 772 000 for
      unfractionated heparin, and $3 105 000 for no prophylaxis. The incremental cost
      per death averted with enoxaparin prophylaxis versus no prophylaxis was $9100.
      Enoxaparin dominated unfractionated heparin by being both more effective and less
      costly in the base-case analysis, as well as in sensitivity analyses in which
      equal efficacy and equal risks of bleeding were assumed. CONCLUSIONS:
      Thromboprophylaxis with this low-molecular-weight heparin represents a cost
      effective use of healthcare resources in acutely ill medical inpatients and
      dominates thromboprophylaxis with unfractionated heparin.

PMID- 15515997
TI  - The role of research in integrated healthcare systems: the HMO Research Network.
AB  - Science is the basis of medicine. Good science leads to better decisions and more
      effective systems to support those decisions. Most individuals associate science
      primarily with academic institutions. However, top-quality research relevant to
      managing the health of populations and the care of specific clinical conditions
      is increasingly being carried out by investigators working in integrated
      healthcare systems. This introduction outlines the activities of the HMO Research
      Network, whose researchers have made and continue to make important contributions
      to the field of health research. Its objective is to inform readers of the
      activities and value of systems-based health research. We describe the importance
      and extent of the research conducted by HMO Research Network members, as well as
      the advantages of conducting research in such settings.

PMID- 15515998
TI  - Closure vs non-closure of the visceral and parietal peritoneum at cesarean
      delivery: 16 year study.
AB  - OBJECTIVE: To determine whether non-closure of visceral and parietal peritoneum
      at LSCS has advantages over peritoneal closure with regard to postoperative
      complication and adhesions. STUDY DESIGN: Prospective randomized controlled
      trial. SETTING: Paholpolpayuhasena Hospital, Kanchanaburi province, Thailand
      SUBJECTS AND METHOD: Three hundred and sixty full-term pregnant women undergoing
      first cesarean section were divided into 3 groups (N = 120). Group A: non-closure
      of both visceral and parietal peritoneum. Group B. non-closure of only visceral
      peritoneum. Group C: closure of both visceral and parietal peritoneum.
      Postoperative complications were compared. Adhesions were evaluated in 65
      patients returning for a second LSCS and compared for severity of adhesions. The
      three groups were compared using statistical analysis. RESULT: There was no
      significant statistical difference between group A and C, group B and C for
      postoperative complications or number of adhesion formation. However, adhesions
      in the closure group were more severe. CONCLUSIONS: Closure of visceral and
      parietal peritoneum has no benefit over non-closure of visceral peritoneum and
      non-closure of both visceral and parietal peritoneum at LSCS.

PMID- 15515999
TI  - Oral salbutamol for treatment of preterm labor.
AB  - OBJECTIVE: The aim of this study was to assess the value of oral salbutamol for
      the inhibition of preterm labor. MATERIAL AND METHOD: Medical records of the
      department from January 1, 1991 to December 31, 1999 were reviewed for all
      idiopathic preterm labors that were inhibited by oral salbutamol and
      statistically analyzed. RESULTS: Of 132 pregnancies, 81.1% (95%CI, 74.4, 87.7)
      were prolonged for more than 24 hours, 59.8% (95%CI, 51.5, 68.2) for more than 2
      days, 32.6% (95%CI, 24.6, 40.6) for more than 1 week, and 8.3% (95%CI, 4.2, 14.4)
      for more than 4 weeks. Tachycardia (pulse rate > 100 beats/min) occurred in 85.6%
      of the patients, but those with a pulse rate higher than 140 beats/min occurred
      in only 3%. Hypotension occurred in only 0.8%. Neonatal complications occurred in
      28%, while respiratory distress syndrome occurred in 22.7% of the babies.
      Perinatal mortality in the present study was 7.6 per 1,000 births. When comparing
      the pregnancy outcome between groups regarding the prolongation time, the
      pregnancy outcome was significantly better in the group that had a prolongation
      time of at least 48 hours. CONCLUSION: Oral salbutamol proved to be another
      effective method that inhibits preterm labor and consequently prolongs pregnancy.
      Because it requires no intensive medical nursing care and observations, and no
      discomfort of an intravenous line, oral salbutamol may be an alternative drug in
      the management of preterm labor.

PMID- 15516000
TI  - Incidence of gestational diabetes mellitus diagnosed before 20 weeks of
      gestation.
AB  - The objectives of this study were to determine the incidence of gestational
      diabetes mellitus (GDM) before 20 weeks of gestation and evaluate associated risk
      factors. A total of 1200 pregnant women who started their antenatal care at
      Siriraj Hospital before 20 weeks of gestation and were at risk of developing GDM
      were enrolled. A 50-gram glucose challenge test was used as a screening method
      and 100-gram oral glucose tolerance test was used to diagnose the condition. All
      women were screened during their first visit and again at 28-32 weeks of
      gestation. The results showed that the incidence of GDM diagnosed before 20 weeks
      of gestation was 5.3% (95% CI 4.1-6.7%), and another 4.9% were diagnosed during
      28-32 weeks. This demonstrated the usefulness and effectiveness of the current
      guideline for GDM screening that approximately half of women with GDM could be
      diagnosed early in their pregnancies. The 2 independent risks for developing GDM
      before 20 weeks of gestation were age > or = 30 years and GDM in previous
      pregnancy (adjusted OR 2.5, 95% CI 1.3-5.0, and 7.1, 95% CI 1.8-27.6,
      respectively). This specific group of women should be counseled regarding the
      importance of early GDM screening during their pregnancy.

PMID- 15516001
TI  - Effect of 3-day intensive dietary therapy during admission in women after
      diagnosis of gestational diabetes mellitus.
AB  - OBJECTIVE: To determine the impact of 3-day intensive dietary therapy during
      admission on glycemic control. MATERIAL AND METHOD: GDM women, with level of
      fasting blood glucose (FBS) at or above 105 mg/dl on their oral glucose tolerance
      test (OGTT), were hospitalized. After 3-day intensive dietary therapy, the women
      were stratified by FBS value and mean 2-hour postprandial blood glucose. Those
      with poor glycemic control, FBS at or above 105 mg/dl, were prescribed insulin
      therapy. RESULT: Between 1 August 2001 to 31 December 2002, a total of 9861
      pregnant women were screened for clinical risk factors of GDM at their first
      antenatal visits, and 4663 had at least 1 risk. After 50-gm glucose challenge
      test and 100-gm OGTT GDM was diagnosed in 300 women. Only 18% (54 in 300 cases)
      of GDM had level of FBS at or above 105 mg/dl on OGTT. They were admitted in a
      special ward for further investigation and initial management. After 3 days of
      intensive dietary therapy, the FBS and mean 2-hour postprandial blood glucose
      level were monitored and stratified in 3 groups. Only 42.6% of admission group
      (23 in 54 cases) still had FBS at or above 105 mg/dl and required insulin therapy
      (group 1). One third (18 in 54 cases) could avoid insulin therapy due to the
      level of FBS below 105 mg/dl and mean 2-hour postprandial blood glucose below 120
      mg/dl (group 2). This second group was discharged, and due to attend the high
      risk pregnancy clinic a few weeks later The third group (group 3), comprising one
      fourth (13 in 54 cases), had FBS below 105 mg/dl but had a mean 2-hour
      postprandial blood glucose at or above 120 mg/dl. This third group were also
      discharged and were monitored glycemic profile by FBS and 2-hour postprandial
      blood glucose every time during their visits to the high risk pregnancy clinic.
      According to criteria of 2-hour postprandial blood glucose at or above 120 mg/dl
      on two or more occasions within a 1-2 weeks interval, no one in group 3 needed
      insulin therapy afterward CONCLUSION: GDM women with FBS at or above 105 mg/dl on
      their OGTT, should be prescribed intensive dietary therapy alone for 3 days
      inside hospital rather than initiating insulin immediately after diagnosis. One
      third had a benefit of avoiding insulin therapy. Only 42% failed to achieve good
      glycemic control and still needed insulin therapy. One fourth showed optimal
      glycemic control after this intervention (FBS below 105 mg/dl) but had mean 2
      hour postprandial blood glucose at or above 120 mg/dl. Longer trial of dietary
      therapy should be considered in this last group to avoid over treatment of
      insulin therapy.

PMID- 15516002
TI  - Occurrence of extended-spectrum beta-lactamase in clinical isolates of Klebsiella
      pneumoniae in a University Hospital, Thailand.
AB  - The occurrence and antimicrobial susceptibility of extended-spectrum beta
      lactamase (ESBL)-producing Klebsiella pneumoniae in patients attending Siriraj
      Hospital in Bangkok from August 2000 to January 2001 were determined. ESBL
      producing isolates were screened with four different methods: disk diffusion
      according to the National Committee for Clinical Laboratory Standards (NCCLS)
      guidelines, Etest ESBL (CT/CTL and TZ/TZL), Oxoid combination discs and MIC Etest
      strip. Antimicrobial susceptibility testing were determined by a microdilution
      automatic method (VITEX system, bioMerieux). Of 22,178 clinical specimens, 400
      (1.8%) K. pneumoniae were isolated Of 26% (104/400) of these isolates were
      suspected to be ESBL-producing. Rates of detection of ESBL-producing K.
      pneumoniae were 18.67%, 30% and 23.78% for blood, sputum and urine samples,
      respectively. Susceptibility testing has revealed that all 70 tested isolates
      including 53 isolates from blood and sputum and 17 isolates from urine samples
      were susceptible to imipenem (MIC< or =4 mg/L). None of the tested isolates were
      susceptible to cephalosporins, cephamycin and aztreonam. Rate of susceptibility
      to ciprofloxacin, levofloxacin, gentamicin and tobramycin were 60%, 64%, 28% and
      9%, respectively, for isolates from blood and sputum; 71%, 71%, 18% and 6% for
      urinary isolates. The present findings revealed a high occurrence rate of multi
      drug resistance ESBL-producing K. pneumoniae in patients attending the university
      hospital. Imipenem was highly active against ESBL-producing K. pneumoniae.

PMID- 15516003
TI  - Percutaneous versus open bone grafting in the treatment of tibial fractures: a
      randomized prospective trial.
AB  - PURPOSE: To compare the results between percutaneous bone grafting and open bone
      grafting of tibial shaft fractures. METHOD: Thirty tibial fractured shafts with a
      delayed union or a high-energy tibial fractures which required early prophylaxis
      bone grafts were randomized to either percutaneous bone graft (n= 15) or open
      bone graft (n=15). One patient from the open bone graft group was lost to follow
      up. Characteristics of the patients were similar in both groups. RESULTS: The
      mean length of follow-up was 2.5 years. Percutaneous bone graft technique was
      associated with significantly less blood loss (p<0.01) and shorter operative time
      (p<0.01). One patient in the percutaneous group had posterior tibial nerve palsy
      postoperatively, which recovered completely after 6 weeks. There were no
      differences in rate of union, healing time of the successful cases, postoperative
      pain and hospital stay. CONCLUSION: The percutaneous technique has effective
      results similar to the open technique in promoting union of tibial fractures. It
      should be considered as a useful alternative to the open bone graft technique.

PMID- 15516004
TI  - Comparison between intravenous recombinant human erythropoietin and subcutaneous
      injection in Thai hemodialysis patients.
AB  - OBJECTIVE: To compare the efficacy, safety and side effects between subcutaneous
      and intravenous route of erythropoietin administration in Thai hemodialysis
      patients. DESIGN: Retrospective study. MATERIAL AND METHOD: Retrospective study
      of hemodialysis patients who switched the route of erythropoietin administration
      from subcutaneous to intravenous in the Renal Unit Department of Medicine,
      Bangkok Metropolitan Medical College and Vajira Hospital and Thammasat University
      was carried out. All patients' information was obtained from the medical records.
      RESULTS: 60 patients with stable hematocrit level in the last 3 months of the
      subcutaneous phase who were switched to intravenous route of erythropoietin
      administration for at least 6 months were recruited The mean hematocrit level of
      patients in the last 3 months of the subcutaneous period was 30.49+/-4.21%. After
      switching to the intravenous route for 6 months, the mean hematocrit level was
      30.24+/-4.99%. Two patients had to increase the erythropoietin dosage and no side
      effects were found in the present study. The mean dosage of erythropoietin
      administered intravenously was not statistically different from the subcutaneous
      route. There was no correlation between age, sex, cause of renal failure,
      transferrin saturation, reticulocyte count, C reactive protein and the dosage of
      erythropoietin, together with the hematocrit level. No other side effects were
      encountered during the intravenous phase. CONCLUSIONS: This study has shown that
      the subcutaneous erythropoietin in hemodialysis patients can be changed to the
      intravenous route in the same dosage with good response and stable hematocrit.

PMID- 15516005
TI  - Surgical outcome of traumatic aortic disruption of the thoracic aorta in
      Songklanagarind Hospital.
AB  - This retrospective study collected data from 11 patients who underwent TDTA'
      repair from February 1987 to June 2003, 10 patients were men (90.9%) and 1 was a
      woman (9.09%) with a mean age of 32 years. All patients had a blunt injury from a
      violent motor vehicle accident. None of them required thoracotomy at the
      emergency room. Standard chest x-ray was done in every patient and the widening
      of the upper mediastinum was mainly found in 10 patients (90.9%), hemothorax in 8
      patients, blurred aortic knob in 7 patients, lower left main bronchus in 3
      patients, pleural apical cap in 2 patients and pneumothorax in 1 patient, 8
      patients were investigated by CT scan and presented a positive study. 3 patients
      (27.27%) were diagnosed by both aortogram and CT scan anda pseudo-false aneurysm
      was found Multi organ system injury was mainly found in 10 patients (90.91%). 7
      patients (63.64%) had hypovolumic shock on admission, 3 patients died
      postoperation and 2 of them had experience of postoperative paraplegia. Clamp and
      sew technique was used in 6 patients (54.54%). The duration of aortic cross clamp
      time ranged from 19-67 minutes (mean time = 39.30 min.) Pneumonia was the
      significant postoperative complication found in 3 patients, including acute renal
      failure, ARDS (all died) and paraplegia in 2 patients. The duration of the aortic
      cross clamp time that was used in the patients who presented with paraplegia was
      more than 40 minutes. 1 patient had delayed the aortic repair for 3 weeks
      resulting from severe brain contusion. 5 patients (45.45%) died in hospital. 1
      patient died in the operating theatre, 4 of them (36.36%) died during
      postoperatively within 24 hours. The mainly cause of death which occurred in
      every patient was intraoperative cardiac arrest, the others were postoperative
      bleeding, ARDS and arrhythmias. The mean of length of stay in the intensive care
      unit was 6.94 days. The period of hospitalization ranged from 11 to 180 days
      (mean = 62.83 days). The small sample size is the limitation for the present
      study. The authors plan to do prospective study about the factors which influence
      the mortality rate and factors related to postoperative paraplegia in TDTA
      patients at Songklanakarind Hospital.

PMID- 15516006
TI  - Prognostic factors for survival in advanced non-small cell lung cancer.
AB  - OBJECTIVE: To determine the prognostic value for survival of various pretreatment
      characteristics and treatments in advanced non-small cell lung cancer (NSCLC)
      patients. PATIENTS AND METHOD: The retrospective study was conducted by reviewing
      the 81 files of advanced NSCLC patients treated with chemotherapy at the Oncology
      Unit, Rajavithi Hospital. Eighteen clinical variables were investigated and
      analysed as prognostic factors for survival. RESULTS: The first chemotherapy
      regimens for the 81 patients included: etoposide plus platinum derivatives (41),
      new drugs (taxanes or gemcitabine) plus platinum derivatives (39) and one other
      platinum based regimen (1). The overall survival time for all patients was 39.4
      weeks with a 95% confidence interval of 30 to 49 weeks. In the multivariate
      analysis, male gender; bone metastasis and liver metastasis are poor prognostic
      factors. Receiving palliative surgery and achieving objective response to first
      regimen chemotherapy are good prognostic factors. Patients who received either
      old or new drug combinations showed no difference in their survival as determined
      by univariate or multivariate analyses which could be due to limitations in the
      present retrospective study. However; this may show that regimens consisting of
      older, less expensive drug combinations still provide survival advantages in
      advanced NSCLC and should be considered in limited financial circumstances.

PMID- 15516007
TI  - Preliminary efficacy and safety of oral suspension SH, combination of five
      chinese medicinal herbs, in people living with HIV/AIDS ; the phase I/II study.
AB  - OBJECTIVE: To evaluate the preliminary efficacy and safety of the mixture of drug
      extracts from 5 Chinese medicinal herbs (SH), in the treatment of Human
      Immunodeficiency Virus (HIV) infection among people living with HIV/AIDS (PLWHA).
      DESIGN: Open-label study. SETTING: Sanpatong Hospital, Chiang Mai, Thailand.
      SUBJECTS: HIV-1 infected adults with a CD4 cell count of more than 200 cell/mm3
      and HIV-1 RNA > 20,000 copies/ml. MATERIAL AND METHOD: Patients received an oral
      suspension of SH, a combination of 5 Chinese medicinal herbs namely Glycyrrhiza
      glaba L., Artemisia capillaris Thumb., Morus alba L., Astragalus
      membranaceus(Fisch.) Bge., Carthamus tinctorius L., 5 g or 30 ml, in 3 divided
      doses after meals, plus sulfamethozaxole/ trimethoprim, 400/80 mg tablet, once
      daily after breakfast for 12 weeks. During the treatment and the follow up
      period, the absolute CD4 cell count and the plasma HIV-1 RNA were monitored.
      Adverse events were observed. RESULTS: Of the 28 enrolled patients, the number of
      positive response patients with reduction of plasma HIV-1 RNA more than 0.5 log
      during the treatment and follow up period were 4-10 (14.2-35.7%) while the number
      of negative response patients who had plasma HIV-1 RNA rising at least 0.5 log
      were 2-4 (0-14.2%). The means viral load at week 0 (baseline), 12 and 20 were
      4.94, 4.83 and 4.76 log copies/ml, which were slightly declined Whilst, the mean
      absolute CD4 cell count of week 0 (baseline), 4, 8, 12, and 20 fluctuated within
      the baseline, range of 382.1, 404.2, 359.4, 404.1, 360.2 cell/mm3, respectively.
      All subjects had good compliance without any serious adverse events. CONCLUSION:
      Under the condition used, SH drug therapy is safe. Satisfactory positive
      response, by decreased viral load of more than 0.5 log, was found in 14%-35% of
      HIV-positive patients. However, the immunologic response, an increase of CD4 cell
      count was not clearly demonstrated. The clinical benefit of SH needs more
      thorough scientific support before being prescribed as adjunctive therapy for
      treating PLWHA.

PMID- 15516008
TI  - Mantle cell lymphoma in Thai patients.
AB  - Mantle cell lymphoma (MCL) is a disease entity recently introduced into the new
      lymphoma classification, therefore, the clinical features as well as therapeutic
      outcomes in Thai patients with MCL has never been described The authors herein
      retrospectively analysed 21 newly diagnosed patients with MCL at King
      Chulalongkorn Memorial Hospital from January 1997 to December 2002. The median
      age of the patients was 54 years (range, 38-79). Male:female was 4:1. Generalized
      lymphadenopathy (67%) was the most common presenting feature. The majority of
      patients (85%) had advanced disease (stage III, IV, Ann Arbor system). Fifty-six
      percent of the patients were classified as the high- and high-intermediate risk
      group by the international prognostic index. Most patients were treated with CHOP
      (vincristine, cyclophosphamide, doxorubicin, prednisolone) or CVP (vincristine,
      cyclophosphamide, prednisolone) regimen. The overall complete remission rate was
      59%. With a median follow-up of 13 months (range, 1-62 months), the rates of
      overall, progression-free and disease-free survivals were 32%, 9% and 20%,
      respectively. Sixty-seven percent of the patients had relapse/progressive disease
      after follow-up. In conclusion, the clinical features as well as the outcomes of
      Thai patients with MCL were comparable to patients in Western countries. Newly
      diagnosed patients should be treated with novel modalities other than
      conventional CHOP chemotherapy in order to improve the outcomes.

PMID- 15516009
TI  - Fractionated stereotactic radiotherapy for bilateral vestibular schwannomas
      associated with neurofibromatosis type 2: early experiences in Ramathibodi
      Hospital.
AB  - PURPOSE: To evaluate the rates of tumor control and useful hearing preservation
      in patients with bilateral vestibular schwannomas (VSs) associated with
      neurofibromatosis type 2 (NF-2) treated with fractionated stereotactic
      radiotherapy (FSRT). MATERIAL AND METHOD: From August 1998--December 2002 there
      were 5 patients with NF-2 who underwent FSRT (Linac-based system) for bilateral
      CP angle tumors. Median age was 28 (18-47) years. Median tumor volume was 5.4
      (2.2-9.4) cc. Eight lesions received a marginal dose of 44.2-59.9 (median = 46.2)
      Gy in 25-33 fractions. The other 2 lesions received 4.4 and 4.9 Gy/fraction for 6
      fractions in 3 and 2 weeks. Median follow-up was 19 (14-44) months. RESULTS:
      Radiographic and clinical tumor control rate was 90%. One lesion progressed at 7
      months after FSRT and was completely resected Of the 5 lesions with Gardner
      Robertson class I-II hearing before FSRT 2 (40%) retained useful hearing at the
      last follow-up. One patient had left facial spasm at 10 months after FSRT which
      gradually improved. No patient had facial palsy, facial numbness or pain.
      CONCLUSIONS: FSRT provided good tumor control and hearing preservation rate in NF
      2 patients with minimal morbidity. However, a longer follow-up is needed to
      evaluate long term results.

PMID- 15516010
TI  - Simple technique for silicone intubation in congenital nasolacrimal duct
      obstruction.
AB  - OBJECTIVE: To propose a simple and low cost technique of using the simple
      materials in the operating room for silicone intubation in case of nasolacrimal
      duct obstruction in children after failed probing. METHOD: The study was a
      consecutive case series. Three patients with congenital nasolacrimal duct
      obstruction aged 42, 51 and 72 months were referred to the authors. Their
      symptoms persisted after probing twice with or without infracture inferior
      turbinate. The authors decided to insert a silicone tubing by using an 18-gauge,
      intravascular catheter as a channel to place a silicone tubing into the
      nasolacrimal system. Success was defined as a complete resolution of symptoms and
      signs (tearing, crusting, discharge, regurgitation on pressure over the lacrimal
      sac) after silicone intubation. RESULTS: All three patients were free of symptoms
      and signs after insertion of silicone tubing and an average 5.5 months (9, 6, 1.5
      months) after removal of the silicone tubing. There were no intraoperative
      complications. No unplanned silicone tubing removal was needed and also no
      complications associated with silicone stent, such as punctal erosion, corneal
      erosion or granuloma formation occurred. CONCLUSION: This simple and low cost
      technique using an intravascular catheter as a channel to place the silicone
      tubing into the nasolacrimal system in case of congenital nasolacrimal duct
      obstruction in children works well. This new technique is not only inexpensive
      but also effortless with no complications.

PMID- 15516011
TI  - The efficacy of combined low dose of Allopurinol and benzbromarone compared to
      standard dose of Allopurinol in hyperuricemia.
AB  - OBJECTIVE: To compare the efficacy of combined low dose of hypouricemic drugs
      (Allopurinol 100 mg and benzbromarone 20 mg; Allomaron) and standard dose 300 mg
      of allopurinol in hyperuricemia. MATERIAL AND METHOD: A prospective, open study
      of 94 hyperuricemic patients was done at King Chulalongkorn Memorial Hospital.
      Each group of 47 patients was given a combined low dose of hypouricemic drugs
      (Allopurinol 100 mg and benzbromarone 20 mg; Allomaron) and a standard dose 300
      mg of allopurinol. Serum uric acid was measured before and 4 weeks after
      receiving the drugs. The efficacy was measured from the difference of the level
      of serum uric acid before and after receiving the drugs. RESULTS: The patients
      receiving the combined low dose of hypouricemic drugs and standard dose of
      allopurinol showed a mean reduction of serum uric acid of 2.5+/-3.4 mg/dl and
      4.1+/-2.7 mg/dl consecutively. There was a statistically significant difference
      between the 2 groups (P = 0.010). CONCLUSION: This study demonstrates that the
      efficacy of standard dose 300 mg of allopurinol is superior to a combined low
      dose of allopurinol and benzbromarone in lowering the level of serum uric acid
      level.

PMID- 15516012
TI  - Magnetic resonance imaging of the brain in epileptic pediatric patients: review
      of the experience in Ramathibodi Hospital.
AB  - OBJECTIVE: To review a series of epileptic children referred for MR imaging and
      correlate the structural abnormalities from the MRI findings with clinical data
      and EEG. MATERIAL AND METHOD: Retrospective review of MRI of the brain performed
      in children, aged less than 15 years with epilepsy at Ramathibodi Hospital from
      January 1999 to December 2002 was done. There were 100 children (57 girls, 43
      boys) with epilepsy, age range from one month to 14 years, mean 7 years and 5
      months. Diagnosis of seizure type and epilepsy were classified according to
      clinical presentation and EEG. RESULTS: There were 16 children with primary
      generalized seizure, 79 children with partial or complex partial seizures with or
      without secondary generalization. The remaining 5 children had a specific
      syndrome. The most common etiology of all patients was congenital disease,
      especially cortical dysplasia. Among children with partial with or without
      generalization, cortical dysplasia was the most common finding (31%). Mesial
      temporal sclerosis and combined cortical dysplasia with mesial temporal sclerosis
      were found in 24% and 13.9%, respectively. Most of the disease categories showed
      significant concordance of the EEG to the MRI findings, except infectious
      disease. CONCLUSION: The most common etiology of epilepsy in children under 15
      years old was cortical dysplasia. For children with partial or complex partial
      seizure, cortical dysplasia was the most common etiology followed by mesial
      temporal sclerosis and combined cortical dysplasia with mesial temporal
      sclerosis, respectively. MRI provides precise etiologic classifications of
      epilepsy.

PMID- 15516013
TI  - Arthroscopically assisted anterior cruciate ligament reconstruction: comparison
      of bone-patellar tendon-bone versus hamstring tendon autograft.
AB  - BACKGROUND: The bone-patellar tendon-bone (BPTB) and the hamstring tendons are
      commonly used for arthroscopially-assisted anterior cruciate ligament (ACL)
      reconstruction. PURPOSE: To compare the results of arthroscopically-assisted ACL
      reconstruction using bone-patellar tendon-bone and hamstring tendons grafts in
      terms of postoperative knee stability, knee functions and clinical rating scale,
      and patient satisfaction. HYPOTHESIS: There was no difference in the outcomes of
      the two grafts. STUDY DESIGN: Retrospective non-randomized clinical trial.
      MATERIAL AND METHOD: Two groups of patients, 45 in the BPTB group and 30 in the
      hamstring group, were followed for at least one year. RESULTS: The two groups had
      similar pre-operative data except the hamstring group which had a significantly
      shorter duration of injury before operation (9.5 versus 18 months, p < 0.05).
      There was no difference in median pre-operative Lysholm knee score (74 in the
      BPTB group versus 75 in the hamstring group, p > 0.05) and the post-operative one
      (95 in the BPTB group versus 99 in the hamstring group, p > 0.05). There was also
      no difference in the median pre-operative HSS knee score (58 in the BPTB group
      versus 61 in the hamstring group, p > 0.05). Although there was a statistically
      significant difference in the median post-operative HSS knee score between the
      two groups (95 in the BPTB group versus 96 in the hamstring group, p < 0.05),
      this was not clinically significant since both scores were rated as an excellent
      result. Both groups had a significantly improved knee stability and knee
      functions (Lysholm and HSS knee scores). The hamstring group, however, had
      significantly higher patient satisfaction (88% in the BPTB group versus 93% in
      the hamstring group, p < 0.05). CONCLUSION: Both the BPTB and the hamstring
      tendon grafts resulted in significantly improved knee stability and functions
      with high patient satisfaction. The hamstring tendon group, however, had a
      significantly better post-operative patient satisfaction (Visual Analog Scale,
      VAS).

PMID- 15516014
TI  - High level of CA 125 due to large endometrioma.
AB  - BACKGROUND: CA 125 is a tumor-associated antigen. Its high levels are usually
      associated with ovarian malignancies, whereas smaller increases in the levels
      were associated with benign gynecologic conditions. The authors report a high
      level of CA 125 in a case of large ovarian endometrioma. CASE REPORT: A 45-year
      old nulliparous Thai woman, presented with an increase of her abdominal girth for
      7 months. Transabdominal ultrasonogram demonstrated a large ovarian cyst and
      multiple small leiomyoma uteri, and serum CA 125 level was 1,006 U/ml. The
      preoperative diagnosis was ovarian cancer with leiomyoma uteri. Exploratory
      laparotomy was performed. There were a large right ovarian endometrioma, small
      left ovarian endometrioma and multiple small leiomyoma. Total abdominal
      hysterectomy and bilateral salpingo-oophorectomy was performed and histopathology
      confirmed the diagnosis of endometrioma and leiomyoma. The serum CA 125 level
      declined to non-detectable at the 4th week. She was well at discharge and
      throughout her 4th week follow-up period CONCLUSION: Although a very high level
      of CA 125 is associated with a malignant process, it can also be found in benign
      conditions such as a large endometrioma. The case emphasizes the association of
      high levels of CA 125 with benign gynecologic conditions.

PMID- 15516015
TI  - Concurrent chromomycosis and aspergillosis of the maxillary sinus.
AB  - The authors describe a rare case of an infection of both the chromomycosis and
      aspergillosis of the maxillary sinus in an immunocompetent 72-year-old female who
      presented with progressive visual loss and dull aching pain of the left eye.
      Sinuscopy of the left maxillary sinus showed swelling of the mucosa with clay
      like materials. Biopsy from the left maxillary sinus showed the typically
      characteristic morphology of chromomycosis and culture from sinus tissue which
      yielded Aspergillus. The patient responded to a combination therapy of surgical
      excision and antifungal agent.

PMID- 15516016
TI  - Primary cardiac angiosarcoma with systemic metastases; a case report and review
      of the literature.
AB  - Angiosarcoma is a relatively uncommon primary malignant tumor of the heart
      derived from the endothelial cells. The authors report a case of primary cardiac
      angiosarcoma of the right atrium with pulmonary, hepatic, cerebellar and bony
      metastases in a 46-year-old man who clinically presented as pulmonary hemorrhage.
      The patient's occupational history had occasional exposure to polyvinyl chloride.
      The autopsy examination of the cardiac angiosarcoma characterized macroscopically
      by a right atrial tumor and histologically by anastomosing vascular channels and
      minute atypical pleomorphic endothelial cells. Immunohistological stainings were
      positive CD31, CD34 and focal positive factor VII-related antigen. Clinical and
      pathologic features with briefly reviewed relevant literatures are discussed This
      is the first reported description in the literature of a primary cardiac
      angiosarcoma with systemic metastases to multiple organs in Thailand.

PMID- 15516017
TI  - Solitary pancreatic metastasis from renal cell carcinoma 14 years after
      nephrectomy: a case report.
AB  - We report a case of solitary pancreatic metastasis from renal cell carcinoma
      which occurred 12 years after radical nephrectomy. The patient had no symptom.
      The lesion was unrecognized until 2 years later. Distal pancreatectomy was
      performed and the patient was still doing well 2 years after that operation. We
      also review the relevant literatures about prognosis, surveillance and choice of
      treatments for pancreatic metastasis from renal cell carcinoma.

PMID- 15516018
TI  - [e-learning of faculty of medicine Chulalongkorn University].
AB  - The teaching policy of facult of medicine, chulalongkorn university had long been
      established, with frequently up-to-date to provide the learning and teaching
      opportunity to medical students and teaching personnels and even the postgraduate
      training course. At the same time, the faculty had a commitment to increase its
      numbers of high quality medical graduates and post graduate medical students. The
      teaching and training course must be shortened and concise to fulfil the new
      trends of teaching curriculum which was recently re-arranged in this faculty. The
      world-wide, available contemporary technology, information and communication
      technology (ICT), is considered to utilized their ability. Learning and teaching
      by this technological trends are increasing in recent years in many developed and
      developing countries. Students, trainees and educators can access these new
      modern technology in anytime and anywhere by connecting internet network, and
      also by this way, they can continue their medical learning, training and gaining
      up-to-date medical technique and knowledge till their life. The process of
      utilizing and incorporating these available programme techniques, such as,
      hypertext, webboard, chat room and e-mails, for education purpose, is named as e
      learning, or some may called it, e-education, e-school, etc.

PMID- 15516019
TI  - A disputable medical profession.

PMID- 15516020
TI  - Regulatory evaluation of efficacy and safety of new drugs in Thailand.

PMID- 15516021
TI  - Uropharmacology: current and future strategies in the treatment of erectile
      dysfunction and benign prostate hyperplasia.
AB  - Because of the increasing percentage of the world male population suffering from
      erectile dysfunction (ED) and benign prostate syndrome (BPS), there is a need for
      new and innovative therapeutic approaches. Pharmacotherapy is an avenue presently
      being followed in the treatment of both these syndromes. A profound change in the
      therapy of ED has been obtained through use of the selective phosphodiesterase
      inhibitor sildenafil. The incidence of surgical intervention in BPS has been
      reduced by the introduction of uroselective alpha1-receptor antagonists and the
      new 5alpha-reductase inhibitors (such as finasteride, dutasteride). The
      investigation of mechanisms in CXC chemokine expression also offers new
      therapeutic possibilities in these diseases.

PMID- 15516022
TI  - Tolerability, pharmacokinetics and concentration-dependent hemodynamic effects of
      oral CF101, an A3 adenosine receptor agonist, in healthy young men.
AB  - OBJECTIVES: To assess safety, tolerability, pharmacokinetics and hemodynamic
      effects of oral CF 101, an A3 adenosine receptor (A3AR) agonist, in healthy men.
      METHODS: One single and 1 repeated dose, parallel-group, ascending dose, double
      blind and placebo-controlled study in normal volunteers. In the single dose
      study, n = 15 subjects received 1, 5 or 10 mg oral CF101; in each group 1 subject
      received placebo, the remainder active CF101. In the repeat-dose study, n = 28
      subjects received repeated 12-hourly oral doses of CF 101 (2, 3, 4 or 5 mg) for 7
      days, in each group 2 subjects received placebo, the remainder active CF101. TEST
      MATERIALS: Single-dose study: CF101 in 30% Cremophor RH40. Multiple-dose sudy:
      CF101 in 0.5% methylcellulose suspension. Both studies: the corresponding
      vehicles were used as placebos. Galenicals were prepared remotely from the
      clinical study site to ensure double-blind nature of the study. RESULTS
      TOLERABILITY: Single doses up to 5 mg CF101 were safe and well-tolerated.
      However, the single dose of 10 mg CF101 was associated with flushing,
      tachycardia, nausea and vomiting, which were viewed as dose-limiting in normal
      volunteers. Single doses of CF101 (as well as the first of the multiple doses)
      were associated with increases in heart rate (8 - 24 beats/min after 5 mg and 18 
      55 beats/min after 10 mg). Multiple doses up to 4 mg 12-hourly for 7 days were
      safe and well-tolerated. However, the 5 mg multiple-dose group reported headache,
      drowsiness, hot flushes and dizziness on standing; this declined with dosing
      duration and was not dose-limiting in this study. Adverse events were commonest
      near t(max). RESULTS PHARMACOKINETICS: For oral CF101, the t(max) was always 1 -
      2 h post-dose and t 1/2 about 9 h, in both the single- and multiple-dose studies.
      For a single 5 mg dose (mean +/- SD) C(max) = 81.6 +/- 23.6 ng/ml in the single
      dose study, and 63.6 +/- 22.0 ng/ml after the first of the multiple doses; AUC if
      was 904.0 +/- 221.9 ng.h/ml and 596.1 +/- 196.6 ng.h/ml for the 2 studies,
      respectively. After 7 days of multiple dosing there was little change, and AUC(0
      24h) = 601.0 +/- 163.6 ng.h/ml. These pharmacokinetic parameters were linearly
      proportional to dose in the other treatment groups. RESULTS PHARMACODYNAMICS:
      Increases in heart rate were related to plasma concentration and evident only in
      the upper range of concentrations observed. There were no changes on ECG
      monitoring beyond sinus tachycardia, and, in particular, no evidence of PR
      prolongation in any subject (n = 43). In comparison with single doses, this
      response was almost absent after 7 days of dosing. Leucocytosis (increases up to
      about 1.5 x 10(9)/l after 5 and 10 mg) was similarly transient and reversible
      after multiple dosing. CONCLUSIONS: Single oral doses up to 5 mg CF101 and
      repeated doses up to 4 mg 12-hourly for 7 days were safe and well-tolerated.
      Multiple-dose CF101 pharmacokinetics were unchanged and predictable from single
      dose estimates, and were linearly proportional to dose. Increases in heart rate
      and neutrophil count were reversible during multiple dosing and were not dose
      limiting in the repeat dose study. CF101 warrants further study for its efficacy
      in treating human disease.

PMID- 15516023
TI  - Absorption pattern of trospium chloride along the human gastrointestinal tract
      assessed using local enteral administration.
AB  - BACKGROUND AND OBJECTIVES: The antimuscarinic drug trospium chloride is
      hydrophilic and therefore does not enter the CNS when used for the treatment of
      overactive bladder disturbances. However, the same property is the main reason
      for low and variable oral bioavailability. The present study was performed to
      assess the influence of intestinal site on absorption of the drug as the basis
      for the development of modified release preparations. METHODS: In a change-over
      pilot study, 8 healthy male volunteers received single 20 mg doses oftrospium
      chloride orally as a tablet (reference), as Eudragit-coated tablets dissolving at
      pH 6.0 (local administration into the small intestine), and rectally via a mini
      enema (corresponding to local administration into the large intestine). Plasma
      concentrations of trospium chloride were determined up to 36 hours after
      administration using GC/MS. RESULTS: Extent and rate of trospium chloride
      absorption declined rapidly upon administration into more distal regions of the
      gastrointestinal tract. C(max) (median: 6.42 ng/ml) and AUC(0.tlast) (42.28 ng/ml
      x h) were highest and t(max) (3.5 h) was shortest after administration of the
      reference tablet. AUC(0-tlast) reached 78% (90% CI 43 - 139%) after small
      intestine administration and 2% (90% CI 1 - 9%) following rectal administration,
      respectively, relative to the values for the oral tablet. CONCLUSION: Trospium
      chloride is absorbed primarily in the upper gastrointestinal tract. Development
      of modified release preparations must balance prolonged apparent absorption rates
      of the drug against a decrease in bioavailability.

PMID- 15516024
TI  - Serum albumin-adjusted phenytoin levels: an approach for predicting drug efficacy
      in patients with epilepsy, suitable for developing countries.
AB  - INTRODUCTION: The antiepileptic drug phenytoin has a high degree of plasma
      protein binding. Therefore, total phenytoin levels in plasma are misleading
      indicators of clinical efficacy. This study was designed to investigate whether
      serum albumin-adjusted phenytoin levels in Indian patients with epilepsy predict
      clinical outcome better than total phenytoin levels. PATIENTS AND METHODS: Fifty
      patients with epilepsy were included in the study and were followed-up for a
      period of 6 months. Serum albumin levels were estimated spectrophotometrically
      using the bromocresol green dye method, and serum phenytoin levels were estimated
      using high pressure liquid chromatography. Values were expressed as mean +/- SEM.
      Corrected phenytoin levels were calculated using the Sheiner-Tozer equation.
      Corrected phenytoin levels = Measured total phenytoin(micromol/l) [(albumin g/1 x
      0.9)+ 0.1] 40. RESULTS: At Visit 1, mean serum albumin levels were 44.1 +/- 1.1
      micromol/l and mean serum phenytoin levels were 33.9 +/- 2.8 g/l. After
      correction of the total phenytoin levels using the Sheiner-Tozer equation, 30% of
      the patients shifted to a different category. The follow-up visits showed similar
      results. Throughout the study, the corrected phenytoin levels were better
      indicators of clinical outcome than the total levels. In 23% of patients there
      was a significant difference between total and corrected phenytoin levels.
      CONCLUSION: In patients with serum albumin levels in the hyper- and
      hypoalbuminemic range, corrected phenytoin levels were better indicators of
      clinical outcome. In developing countries like India, where estimation of free
      drug levels is expensive and suitable equipment is not available in most centers,
      serum albumin-adjusted levels can be used by pharmacologists to predict response
      and thus assist in clinical decision-making.

PMID- 15516025
TI  - Pharmacokinetics of teicoplanin during continuous hemofiltration with a new and a
      24-h used highly permeable membrane: rationale for therapeutic drug monitoring
      guided dosage.
AB  - OBJECTIVE: Continuous venovenous hemofiltration (CVVH) is widely used in the
      management of critically ill patients, but only few administration guidelines for
      antimicrobial drugs are available. It is unclear whether the use of a filter for
      more than 24 hours might lead to less efficient extraction. This study describes
      the pharmacokinetics of teicoplanin during CVVH using a highly permeable
      membrane. METHODS: Pharmacokinetics of teicoplanin during continuous
      hemofiltration with a new (group 1) and a 24-h used (group 2), highly permeable
      polyamide membrane were assessed in 3 patients. RESULTS: The teicoplanin serum
      concentrations (44.0 +/- 18.5 mg/l vs 109.5 +/- 34.5 mg/l) and half-life of
      teicoplanin (4.6 +/- 1.1 h vs 5.2 +/- 0.7 h) differed significantly between the 2
      groups indicating a smaller elimination of the drug on the second day.
      Substantial binding of teicoplanin to filter membranes could explain this
      observation. CONCLUSION: The results suggest that daily adjustment of the dosage
      is necessary to achieve sufficient teicoplanin concentrations and a fixed dosage
      recommendation is not suitable for this drug.

PMID- 15516026
TI  - Phenotype-genotype relationships of SULT1A1 in human liver and variations in the
      IC50 of the SULT1A1 inhibitor quercetin.
AB  - Human sulfotransferases catalyze sulfate conjugation and 2 polymorphic genes,
      SULT1A1 and SULT1A2 in this family of transferases have been identified, encoding
      for 2 isoenzymes with very similar properties and substrate specificities. In
      order to test the hypothesis that variability in sulfation is due to genetic
      polymorphism in SULT1A1, the sulfation rate of 4-nitrophenol, a diagnostic
      substrate, was measured in 50 human liver samples and the genotype at the SULT1A1
      locus was analyzed. The rate of 4-nitrophenol sulfation varied from 473 - 1,405
      pmol/min/mg between the 5th and 95th percentiles, with a median and a mean +/- SD
      of 757 and 807 +/- 292 pmol/min/mg, respectively. The activities detected among
      the SULT1A1*2/*2 homozygotes (5 cases) were significantly lower than those of the
      other 2 genotypes, SULTA1*11/*1 and SULT1A1*1/*2 (5 and 40 cases, respectively),
      whereas there was no significant difference found between the SULT1A1*1/*1 and
      SULT1A1*1/*2 genotypes. To evaluate the possible influence of SULT1A2
      polymorphism, genotype assays were also performed for this locus. No SULT1A2*2/*2
      carrier, 26 SULT1A2*1/*1 and 24 SULT1A2*1/*2 were detected in the population
      sample under study. However, no correlation between the rate of 4-nitrophenol
      sulfation and the SULT1A2 genotype was detected. These results confirm that the
      variation in the rate of 4-nitrophenol sulfation in human liver is mainly due to
      SULT1A. Since SULT1A1*1/*2 polymorphism accounts for no more than 10% of the
      phenotypic variation seen in this cohort, other factors must also contribute to
      the variability in the rate of 4-nitrophenol sulfation in human liver. However,
      on the basis of the data obtained, variations in age, gender and liver function
      as possible causative factors can be excluded. The IC50 of quercetin, a potent
      inhibitor of 4-nitrophenol sulfation, was measured in the liver samples and
      ranged from 4.6 to 17.3 nM between the 5th and 95th percentiles. The median and
      the mean +/- SD were 7.7 nM and 8.3 +/- 2.5 nM, respectively. There was a weak
      but significant correlation between the IC50 value and age of the liver donors (r
      = 0.283, p = 0.046). The observed variation did not correlate with the genotypes
      at the SULT1A1 and SULT1A2 loci.

PMID- 15516027
TI  - Valproic acid induces expression of neutrophil chemoattractants of the CXC
      chemokine family in endothelial cells.
AB  - The branched-chain fatty acid valproate (valproic acid; VPA) displays antitumoral
      properties by blocking tumor growth, progression and invasion. Recent data have
      shown that VPA reduces the angiogenic activity of endothelial cells. The object
      of this study was to investigate whether endothelial modulation might also
      influence the level of chemotactic mediators. Endothelial cells were isolated
      from human umbilical cord veins (HUVEC) and treated with VPA-concentrations
      ranging from 0.125 mM to 1 mM. The mRNA level of CXC-chemokines was investigated
      by reverse transcriptase-polymerase chain reaction. The proliferative activity of
      HUVEC was measured as well. VPA evoked a striking increase in the neutrophil
      chemoattractants CXCL1, CXCL3, CXCL4, CXCL5 and a moderate increase in CXCL6 with
      maximal effects after a 3-day incubation period. Other CXC-chemokines and CXC
      receptors remained unaffected. HUVEC growth was diminished time- and dose
      dependently by VPA. We conclude that VPA treatment leads to alterations in the
      chemokine expression profile of endothelial cells. This might allow more
      neutrophils to reach the tumor area and trigger cytolysis.

PMID- 15516028
TI  - Changing trends in the hospital management of unstable angina: a drug utilization
      analysis.
AB  - OBJECTIVE: The current study was designed to investigate drug utilization in the
      management of unstable angina in India and to examine the changing trends in the
      management of unstable angina over the past 4 years. METHODS: We conducted a
      prescription survey to examine the use of antianginal drugs in patients with
      unstable angina in a tertiary care Indian hospital. The use of concurrent
      medications such as antidiabetic, antihypertensive and lipid-lowering agents was
      also examined. This study results were compared with a similar study done in this
      institute 4 years earlier. RESULTS: A total of 159 consecutive prescriptions were
      evaluated. Aspirin (86%), nitroglycerin infusion (77%) and low-molecular weight
      heparins (93%) were the most frequently prescribed drugs. Enoxaparin accounted
      for 76% of the total LMWH use. One of the heparins was used by 92% of all
      patients, angiotensin-converting enzyme inhibitors (ACEIs) and beta-blockers by
      70% and 67%, respectively. Lipid-lowering agents (57%), antidiabetic agents (16%)
      and antianxiety agents (33%), in addition to antianginals, were also frequently
      co-administered. Time trend analysis showed that the use of unfractionated
      heparin fell from 35% to 10% and the use of ACEIs and enoxaparin increased from
      17% to 70% and from 51% to 71%, respectively. CONCLUSIONS: The study showed that
      unfractionated heparin is less frequently used in the treatment of unstable
      angina than in the past and that ACEIs are preferred to calcium channel blockers.
      Enoxaparin remains the most commonly used low-molecular weight heparin for this
      indication. A variety of low-molecular weight heparins are available for therapy
      but comparative clinical trials of efficacy and pharmacoeconomic studies
      comparing the various LMWHs still need to be carried out.

PMID- 15516029
TI  - Cluster analysis is a generic term for a wide range of numerical methods for
      examining data.

PMID- 15516030
TI  - Mixture modelling for cluster analysis.
AB  - Cluster analysis via a finite mixture model approach is considered. With this
      approach to clustering, the data can be partitioned into a specified number of
      clusters g by first fitting a mixture model with g components. An outright
      clustering of the data is then obtained by assigning an observation to the
      component to which it has the highest estimated posterior probability of
      belonging; that is, the ith cluster consists of those observations assigned to
      the ith component (i = 1,..., g). The focus is on the use of mixtures of normal
      components for the cluster analysis of data that can be regarded as being
      continuous. But attention is also given to the case of mixed data, where the
      observations consist of both continuous and discrete variables.

PMID- 15516031
TI  - Two-mode clustering methods: a structured overview.
AB  - In this paper we present a structured overview of methods for two-mode
      clustering, that is, methods that provide a simultaneous clustering of the rows
      and columns of a rectangular data matrix. Key structuring principles include the
      nature of row, column and data clusters and the type of model structure or
      associated loss function. We illustrate with analyses of symptom data on
      archetypal psychiatric patients.

PMID- 15516032
TI  - Fuzzy set analyses of genetic determinants of health and disability status.
AB  - Analyses of complex genotype-phenotype relations require new statistical
      procedures because of the potentially high dimensionability of those relations
      which are expressed with both measurement error and stochasticity in the
      correlation function. We propose modifying a multivariate procedure called grade
      of membership (GoM) analysis to deal with the special problems of such analyses.
      In doing so, we make clear some special features of the GoM model for
      multivariate analysis of high dimensional, discrete data. This is illustrated for
      apolipoprotein E (APOE) assessments made on 1805 people in the 1999 National Long
      Term Care Survey. A number of interesting relations with APOE polymorphism were
      found where disability profiles were more predictive than specific diagnoses
      because they implicitly contained information on chronicity and severity of
      disease processes.

PMID- 15516033
TI  - [Home parenteral nutrition in patients with advanced cancer: experience of a
      single centre over ten years].
AB  - The use of Home Parenteral Nutrition (HPN) in patients with advanced cancer
      without the possibility of curative treatment continues to be a controversial
      subject entailing a considerable emotional burden. Nonetheless, this group of
      patients constitutes the main indication for HPN in many programmes. GOAL: To
      present the characteristics of a series of patients included on an HPN programme
      over the last ten years. METHOD: Retrospective study of the case histories of the
      11 patients who received HPN over this period. The demographic and clinical
      details were noted along with their complications and evolution for comparison
      with those of a control group of patients with benign disease receiving HPN over
      the same period. For the comparisons, Student's t test and the chi-squared test
      were used as and when indicated. Results were considered statistically
      significant if p < 0.05. RESULTS: Eleven patients received HPN, nine of them
      because of an irresoluble intestinal obstruction and two because of a high flow
      fistula. The mean age at the start of HPN was 50.8 +/- 12.7 years versus 37.3 +/-
      17.2 years for the group with benign disease (p < 0.05). The mean duration of HPN
      was 71.05 +/- 217 days in the first group, notably less than the second (387.15
      +/- 995.85; p < 0.05), with a range between 5 and 760 days. The patients received
      the infusion through a previously implanted subcutaneous reservoir (n = 9) and on
      two occasions, electively, through a tunnelled catheter. The infection rate was
      higher in the group with cancer (0.34 episodes per patient and 1,000 days on HPN)
      than in the group with benign disease (0.08 episodes; p < 0.05). HPN was
      suspended in only one of the patients more than 5 days prior to death due to
      clinical deterioration. Two patients required admission due to a complication
      associated with the technique. In both cases, a fungal infection of the blood
      made it necessary to withdraw the catheter. The quality of life, measured by
      means of an activity scale, was similar at the start of HPN in both groups. None
      of the patients included on the programme is still alive. CONCLUSIONS: HPN offers
      patients with advanced cancer and severe intestinal dysfunction the possibility
      of an at-home treatment with a low complication rate. If we take into account the
      short mean duration of HPN, inclusion on the programme must be assessed
      individually and regularly revised.

PMID- 15516034
TI  - [Simultaneous haemocultures and diagnosis of catheter-related sepsis].
AB  - OBJECTIVE: To determine the diagnosis value of simultaneous blood cultures.
      BACKGROUND: The clinical criteria is not enough to establish catheter-related
      sepsis diagnosis and remotion or replacement of catheter are not necessary.
      SUBJECTS: We evaluated 164 catheters used for total parenteral nutrition
      placement in 127 patients with cancer. Simultaneous blood samples--central and
      peripheral venous--were taken after seven at ten days of permanency or infection
      suspicion and compared with tip culture result. INTERVENTIONS: Sensitivity,
      specificity and predictive values were calculated. The tip culture was the gold
      standard. RESULTS: A positive central venous blood culture with negative
      peripheral blood culture result was sensitivity of 87.5% and specificity of
      97.9%, an inverse result show a sensitivity of 62.5%. When both blood cultures
      were positive are correctly identified 83.3% of cases with a sensitivity of 93.9%
      and diagnostic correlation of 0.87. CONCLUSIONS: The simultaneous blood cultures
      are high diagnostic value.

PMID- 15516035
TI  - [Application of multivariate analysis to the serum mineral and trace element
      content on differentiation of healthy subjects].
AB  - OBJECTIVE: Serum concentrations of Na, K, Ca, Mg, Fe, Cu, Zn, Se, Mn and P were
      determined in apparently health individuals representing of the population of the
      Canary Islands. Multivariate analysis was applied on the data matrix in order to
      differentiate the individuals according several criteria such as gender, age,
      island and province of residence, smoking and drinking habits and physical
      exercise. SUBJECTS AND METHODS: 395 serum samples (187 men and 208 women) were
      analyzed mean age of 38.4 +/- 20.0 years. Individuals data about age, gender,
      weight, height, alcohol consumption, smoking habits and physical exercise were
      recorded using standardized questionnaires. The determination of minerals was
      carried out by flame emission spectrometry (Na and K) and atomic absorption
      spectrometry with flame air/acetylene (Ca, Mg, Fe, Cu, Zn), hybride generation
      (Se) and graphite furnace (Mn). The P was determined by a colorimetric method.
      RESULTS: The sex and age of individuals influenced on the serum concentrations of
      some minerals, Cu and Fe, and P and Se, respectively. The island of residence
      influenced the mean concentrations of the most the minerals analysed. The smoking
      and drinking habits do not seem to influence the mean contents of the minerals in
      an important manner. Physical exercise had significant influence on the P, Cu and
      Mn concentrations in serum. The water for consumption influenced on the serum
      concentrations of the electrolytes and Ca and Mg, but it did not affect the
      concentrations of the trace elements. Applying discriminant analysis the
      individuals lower 18 years were reasonably well differentiated (89% of the
      individuals correctly classified) from the rest of individuals. A tendency for
      differentiation of individuals according to the island of residence was also
      observed. CONCLUSIONS: A low differentiation of the individuals according to the
      sex, province or island or residence and habits or life style was observed after
      application of multivariate analysis techniques. However, the adults were
      reasonably differentiated from the children and adolescent, and the inhabitants
      of Lanzarote and La Palma tend to separate from the rest of the individuals of
      their province.

PMID- 15516036
TI  - [In vivo study of mitochondrial oxidation in obese patients treated by means of
      calorie restriction].
AB  - The energy restriction is the most common nutritional approach to treat obesity,
      whose efficiency depends on oxidative response against changes in body weight. In
      that context, the aim of the present work was to in vivo examine the
      mitochondrial oxidation of obese volunteers by the 2-keto[1-(13)C]isocaproate
      breath test, before and after weight loss. Thirty-two volunteers (men and women)
      participated: 16 controls (body mass index: 19.0-27.0 kg/m2), and 16 obese (body
      mass index: 30.0-41.6 kg/m2) who followed a caloric restriction program for 10
      weeks (-500 kcal). Before and after dieting, the 2-keto[1-(13)C]isocaproate
      breath test was performed by ingestion of 1 mg/kg tracer and 20 mg/kg L-leucine,
      dissolved in 200 ml orange juice. Breath samples were recovered at baseline and
      at 10 min intervals for 2 h after ingestion. The 13C-enrichment in breath was
      measured by isotope ratio mass spectrometry and the percentage of mitochondrial
      oxidation of tracer (%13C) was calculated. The percentage of oxidized tracer
      marginally tended to be lower in obese than in controls (25.1 +/- 5.5%, vs 27.5
      +/- 4.0%, p = 0.175). After the intervention, the mean of weight loss was -7.8%
      +/- 3% p < 0.001), and the mitocondrial oxidation of the tracer statistically
      increased (25.1 +/- 5.5% vs 34.3 +/- 5.2%, p < 0.001). In fact, the body weight
      and the percentage of oxidized 2-keto[1-(13)C]isocaproate were inversely related
      (r = -0.34, p = 0.018). Thus, the 2-keto[1-(13)C]isocaproate in vivo showed the
      mitochondrial adaptation of obese volunteers treated by caloric-restriction
      intake and provided new information about the weight loss process induced by an
      hypocaloric diet.

PMID- 15516037
TI  - [Assessment of the acceptance of set meals served at the "Sant Joan de Reus"
      University Hospital].
AB  - Despite the fact that, in most of the series published, cancer is the most
      frequent base pathology for the indication of home parenteral nutrition (HPN),
      the use of this technique in terminally-ill patients is still a controversial
      issue. Our goal has been to review the evolution of cancer patients with HPN
      treatment from "La Paz" Hospital with a view to studying the indication,
      evolution and complications. We review a total of 9 terminal oncological patients
      who had been treated with HPN between January 2000 and December 2002, with a mean
      age of 60.4 (44-81) years, the most common base cancer was gastric adenocarcinoma
      (44%). Intestinal obstruction in the context of peritoneal carcinomatosis was the
      reason for indicating HPN in 89% of cases and the median survival time was 71 (23
      131) days. Catheter infection was the most frequent complication with 1.4
      episodes/patient. The existence of a Home Support Team meant follow-up of
      patients was easier, with HPN being estimated as the treatment provided in 67% of
      cases. 56% of the patients were not sufficiently informed as to their underlying
      illness. Although HPN is one more therapeutic resource, which may or may not be
      used in some terminal oncological patients, we must refine the indication as much
      as possible to take into account a series of "systematic guarantees" including
      fulfilment of pertinent clinical criteria, informed consent and the adoption of a
      collective decision with the involvement of all the professionals monitoring the
      patient. We propose an action algorithm to help in improving the decision-taking
      process in these patients.

PMID- 15516038
TI  - [Assessment of home parenteral nutrition programme in terminal oncological
      patients].
AB  - BACKGROUND AND GOALS: The assessment of the acceptance of the diets served at the
      hospital allows the introduction of adjustments to improve the quality of the
      service provided to hospitalized patients by preventing the complications derived
      from incorrect nutrition and enhancing their stay in hospital. The goal of the
      present study was to analyze the acceptance of the menus offered by the
      Hospital's catering service. SCOPE OF THE STUDY: Menus provided by the catering
      service of the "Sant Joan de Reus" University Hospital. MATERIAL AND METHODS: A
      total of 160 tray meals consumed were assessed, all chosen at random and
      corresponding to standard diets and special diets, including pureed food. The
      assessment was made by two dieticians in the hospital's kitchens. A visual scale
      was used with the following scores: 0 for a full plate, 1 for residual food
      amounting to over 75%, 2 from 50% to 75%, 3 more than or equal to 25% and 4 for
      empty plates. RESULTS: A total of 68 trays containing a standard diet were
      analyzed, together with 34 containing special diets and 41 with pureed food. The
      remains on 36 different courses from the standard diet were analyzed. The mean
      acceptance score was 3.01 +/- 1.30 in the case of the first courses, 3.24 +/-
      1.11 in second courses and 3.53 +/- 0.96 for the desserts. As for special diets,
      a total of 27 different courses were analyzed. The mean acceptance score was 2.87
      +/- 1.38 in the case of the first courses, 3.02 +/- 1.27 in second courses and
      3.49 +/- 1.22 for the desserts. The first courses of pureed diets received the
      worst score of all the dishes served, although the overall mean score was good,
      2.76 +/- 1.5. CONCLUSIONS: In general, a good level of acceptance has been
      observed for the set meals served in the hospital. Knowing which courses have
      lower acceptance scores allows changes to be proposed to the hospital menus, with
      their replacement by others with foreseeably better acceptance.

PMID- 15516039
TI  - [Nutritional evaluation of health shift workers from the Canary Islands].
AB  - OBJECTIVE: Shift workers are known to have increased morbidity associated to
      wrong habits. In this study we have evaluated the nutritional status, food habits
      and physical activity in health shift workers. SUBJECTS: 207 permanent morning
      shift workers and 210 shift workers (3-shift system) were randomized selected
      from the 2,100 workers of the North Area of the Canary Island Sanitary Health
      System. METHODS: Dietary intake was assessed by a self-registered food frequency
      questionnaire. We also assessed Body Mass Index, blood lipid levels (total
      cholesterol, HDL cholesterol, LDL cholesterol and triglycerides), physical
      activity, age and sex. RESULTS: Shift workers shown higher intake of red meat,
      eggs, fruit juices and pasta. No differences were observed in lipid levels,
      weight status and physical activity in relation to the shift working status. 62%
      of men and 37.2% of women were overweight or obese. 46% of the subjects were
      sedentary. CONCLUSIONS: Shift work system seems to have little influence on the
      food habits of health workers.

PMID- 15516040
TI  - [Evaluation of palatability of two special oral diets for institutionalized
      elderly diabetics, Glucerna SR vs Resource Diabet].
AB  - OBJECTIVES: To evaluate the organoleptic characteristics of two specific
      nutritional supplements for diabetes (Glucerna SR and Resource Suport) and
      compare them. SETTING: An evaluation was made of 456 patients with Type 2
      diabetes (most of them receiving OADs or insulin) from 34 centers. They were non
      smoking elderly patients (mean age 73 to (71-78) admitted to nursing homes or
      homes for the aged distributed all over the Spanish territory. INTERVENTIONS:
      Palatability was studied using a modified wine tasting scale assessing 6
      parameters (appearance, smell, body, sweetness, aftertaste and taste) that were
      scored individually, with a total score ranging from 0 (most unfavorable) to 20
      (most favorable). Each brand was evaluated in two flavors (vanilla and
      strawberry) according to a crossover, double-blind design. RESULTS: A total of
      906 evaluable observations were made, and highly statistically significant
      differences favorable to Glucerna RS were found in all parameters considered both
      absolutely and relatively, exception for sweetness, for which statistical
      significance was not reached because it was relatively evaluated. No statistical
      differences were found between the two flavors (vanilla and strawberry). The only
      significant confusing factor found was age; the older the age, the more the
      differences were noted between the two brands. CONCLUSIONS: Glucerna SR has a
      better flavor than Resource Suport for institutionalized elderly diabetic
      patients.

PMID- 15516041
TI  - [Ingestion of antioxidants and polyamines in patients with severe burns].
AB  - Starting the first 24 hours after burn injury, energy supply, antioxidants and
      polyamines were assessed in 25 severe burn patients (20 men and 5 women) with a
      mean age of 45.6 +/- 20.4 years. Nutritional assessment was performed at 7, 15
      and 21 days and was compared with a control group (n = 30). In 21 patients the
      burned body surface area was 20%-50% and in four patients it was greater than
      50%. A mean decrease in energy supply of approximately 40% versus the calculated
      theoretical value was found in the three periods: 1,186 +/- 32; 1,117 +/- 589 and
      1,331 +/- 578 kcal. In the first 15 days antioxidant ingestion was slightly lower
      than the recommended daily allowance for vitamin C: 60 mg versus 57 +/- 32, 57 +/
      53 and 75 +/- 53 mg, and was lower during the entire period for vitamin E: 10 mg
      versus 5.0 +/- 2.9; 4.5 +/- 3.0 and 5.3 +/- 3.4 mg; selenium: 40 microg versus
      22.8 +/- 13.7; 22.5 +/- 9.8 and 25.7 +/- 11.2 microg and zinc: 12 mg versus 7.3
      +/- 3.0, 6.8 +/- 4.8 and 8.4 +/- 5.3 mg. Taurine ingestion decreased on day 15
      and significantly increased on day 21: 65.7 +/- 30 mg, 50.9 +/- 25 and 72.0 +/-
      29 mg (p < 0.05). Ingestion of total polyamines did not differ significantly from
      the values observed in the control group and were as follows: day 7, total 45.2
      +/- 23.0 umol, putrescine 16.7 +/- 10.2, spermidine 13.5 +/- 7.6 and spermine
      13.6 +/- 8.8; day 15: total 41.1 +/- 38.5 and 14.9 +/- 4.0, 11.7 +/- 9.4 and
      10.89 +/- 9.0; day 21: total 39.1 +/- 35.3 and 15.4 +/- 16.9, 12.3 +/- 11.4 and
      17.3 +/- 16.8 umol, respectively.

PMID- 15516042
TI  - [General practitioners and vaccination coverage of the population].
AB  - Adults have insufficient vaccination coverage in Belgium today. It is up to the
      general practitioner, who is a key player in the Belgian health system, to ensure
      that this coverage is improved. The most efficient measures are: systematic
      patient notification, population and practitioner instruction, reduced cost for
      the patient, improved access to vaccination services and vaccination reminders to
      practitioners. These measures will be made easier by the development of the
      Global Medical Record and the Computerised Medical Record.

PMID- 15516043
TI  - [Hexavalent combined vaccination].
AB  - Since January 2004, hexavalent combined vaccines are available in Belgium. They
      protect children simultaneously against 6 diseases (poliomyelitis, diphtheria,
      tetanus, pertussis, invasive infections with Haemophilus influenzae type b and
      hepatitis B) and reduce the number of needed injections. Acellular pertussis
      vaccine is the corner-stone of the combination. Theoretically, only 5 visits and
      6 injections are needed to complete the vaccination of the children. In addition
      to the reduction of injections and consequently a better comfort for the child,
      Hexavalent vaccination favours an increase of immunization coverage, alleviation
      of the burden of diseases evitable by vaccination, simplification of immunisation
      programme and diminution of their cost. However an increased surveillance of the
      incidence of the diseases, particularly for pertussis and invasive Haemophilus
      influenzae type b disease is needed. As always for a new product,
      pharmacovigilance has to be able to detect any severe adverse event. Parent's
      information must be strengthened to maintain confidence in the immunization
      programme. Medical practice will have to adapt to the new vaccine because it
      reduces individual flexibility and modifies the catch-up immunization schedule.

PMID- 15516044
TI  - [Pneumococcal conjugate vaccine in children].
AB  - Streptococcus pneumoniae is one of the major causes of severe invasive infections
      in young children. As purified polysaccharide are not immunogenic in infants,
      vaccines containing the bacterial polysaccharide conjugated to a carrier protein
      have been developed according to the model that has proved to be effective for
      Haemophilus influenzae b and group C meningococcus. A conjugate vaccine
      containing the 7 serotypes responsible for about 90% of the invasive infections
      occuring in children in the United States has been shown to have a 97% protective
      efficacy against infections caused by vaccine serotypes. Pneumococcal conjugate
      vaccines are also protective, although to a lesser extent, against otitis media
      caused by vaccine serotypes, but the global impact of these vaccines on the total
      number of otitis media remains limited. The large scale use of this vaccine has
      demonstrated its epidemiological impact on the burden of invasive pneumococcal
      disease in the age group targeted by vaccination as well as among the adult
      contacts of the vaccines. On the basis of these informations, the conjugate
      pneumococcal vaccine has been included in the recommended vaccination schedule in
      Belgium. However, repeated vaccine shortages as well as the high cost of the
      product make the implementation of this recommendation uncertain.

PMID- 15516045
TI  - [Varicella vaccination].
AB  - Varicella is a highly contagious disease due to varicella-zoster virus (VZV)
      belonging to the herpesvirus family. Following infection, the virus remains
      latent in neural ganglia, and upon subsequent reactivation VZV may cause zoster.
      While mostly a mild disorder in childhood, varicella tends to be more severe in
      adults. Healthy individuals may develop complications such as bacterial
      superinfections, pneumonia or encephalitis. Varicella may be fatal, especially in
      neonates and in immunocompromised persons. Control of varicella can be achieved
      only by widespread vaccination. The purpose of this review is to summarize the
      impact and the concerns of an universal varicella vaccination. The vaccines are
      based on the attenuated Oka-strain. The positive results of extensive safety,
      efficacy and cost-effectiveness analyses have warranted the introduction of these
      vaccines in the USA in 1995 and, more recently, in Australia and in Canada.
      However, European countries have some concerns. At low levels of coverage, there
      is a possible shift of the disease in older children and adults. At high levels
      of coverage, without natural exposure to the wild virus, the duration of the
      protection against varicella in vaccinated children could wane and zoster in
      elderly could increase. Recent reports suggest that a booster dose or a two doses
      regimen would be better for adequate immunisation in childhood. Vaccines
      combining measles, mumps, rubella and varicella are currently under studies and
      would warrant a high coverage.

PMID- 15516046
TI  - [Pneumococcal polysaccharide vaccine].

PMID- 15516047
TI  - [Pertussis vaccine in adolescents and adults].
AB  - Despite high immunisation rates in infancy, Bordetella pertussis is still
      circulating in industrialised countries, causing severe infections in infants too
      young to be vaccinated, as well as an important number of long lasting cough
      episodes in older children, adolescents and young adults. The limited duration of
      the protection resulting from vaccination in the 2 first years of life is
      probably responsible for the insufficient control of the disease. The development
      of acellular pertussis vaccines has allowed immunisation of school age children,
      and an adult formulation is now available. The indications of this vaccine will
      be discussed.

PMID- 15516048
TI  - [Vaccination of general practitioners].
AB  - The vaccination of general practitioners represents significant problems for two
      reasons: they can be a reservoir of infectious diseases for the patients they are
      in contact with and their attitudes towards vaccination can influence their
      preventative acts and consequently the vaccination coverage of the population.
      The anti-influenza vaccination of the care providers is associated with a
      decrease of mortality amongst patients. Hepatitis B is one of the most frequent
      professional occupational infectious diseases and vaccination is necessary for
      all the professionals at risk. Concerning the whooping-cough we can observe at
      the present time an increase in the number of cases. The "Conseil Superieur
      d'Hygiene" advises to propose vaccination of the people in contact with infants
      and people who have not HAD vaccination supplements in childhood. The rubella
      vaccination for unprotected women is also recommended for the care providers, to
      avoid the risk of infection and the possible implications for the foetus. The
      existing data in Belgium on the vaccination coverage of general practitioners is
      poor, but leads us to believe there is an insufficient vaccination coverage
      against these diseases. A study will shortly be undertaken to analyze the
      vaccination status of the Belgian French-speaking doctors and to further analyse
      their reasoning for any possible non-vaccination.

PMID- 15516049
TI  - [Angioedema in daily practice].
AB  - The principal pathophysiologic mechanisms accounting for most cases of angioedema
      are reviewed as for their clinical presentations owing to the involved process.
      The features of the cutaneous reactions induced by foods or drugs to which the
      subjects are allergic, are discussed. The particular case of the amoxicillines
      reactions as well as the mechanisms by whom the aspirin, the NSAIDs and the ACE
      inhibitors induce angioedema are reminded. The description of cases lived in
      clinical practice illustrates the work and demonstrates the importance of
      anamnesis in the diagnostic approach of this affection.

PMID- 15516050
TI  - [Moulds asthma].
AB  - Mould allergy revealed by skin prick tests or by measuring specific IgE (RAST),
      is frequently diagnosed throughout the world. It is associated to clinical
      asthma, sometimes severe. Thanks to the know how of teams of specialists, surveys
      are carried out in home-, work- and school environments, and calendars of moulds
      found in our country are regularly updated. This allows practitioners to
      determine specific sensitisation tests (selection of skin prick tests, and RAS
      tests), and helps them play a role in the diagnosis strategy and the
      recommendations for necessary eviction and building sanitation measures. These
      measures are all the more important as until now standardised extracts for
      specific hyposensitisation to moulds are not yet available.

PMID- 15516051
TI  - [Sublingual hyposensitization].
AB  - Specific hyposensitization remains the only way to alter profoundly the progress
      of the allergic disease. The last discoveries in immunology allow better to
      understand the mechanisms of action. Now, we can use more purified and
      standardised solutions to improve the results. Subcutaneous way remains the gold
      method. But, since 10 years, European screws publishes the results of their works
      about alternative ways like sublingual way. Less dangerous and less compelling,
      it allows to begin the treatment earlier in the live and to give more important
      doses. The results are equivalent to the subcutaneous method. Recently, W.H.O.
      decided to consider sublingual immunotherapy as un full treatment of some
      allergic diseases.

PMID- 15516052
TI  - [Hair physiology].
AB  - The first hair follicles appear on the body toward the end of the 8th week of
      intrauterine life. The appearance on the scalp is more tardive 7th month. The
      hair is a keratin-containing appendage that grows from cavities called follicles.
      Hair follicles extend from the surface of the skin through the stratum corneum
      and the epidermis into the dermis. Keratin contains almost all aminoacids but
      particularly rich in cystein. Hair fibers grow in three distinct stages. The
      first one, the anagen stage, is the growing phase with a duration of 3 to 5
      years. The catagen stage, the transition stage, lasts only a few weeks; it
      precedes the telogen stage, resting or shedding phase, lasts for 2 months.

PMID- 15516053
TI  - [Place of microscopic hair analysis].
AB  - Managing hair loss often necessitates additional techniques to achieve proper
      diagnosis. The trichogram procedure evaluates the type of perturbation in hair
      cycle, gives clue to diagnosis and permit to follow the evolution of pathological
      process. Polarized light microscopy analysis of pilary shaft contributes to the
      diagnosis of pilar dysplasias. Scalp biopsy is particularly indicates in cases of
      cicatricial alopecia.

PMID- 15516054
TI  - [Clinical tools for assessing hair loss].
AB  - The complaint of hair loss is quite frequent but merits close attention because
      it can be very stressful to the patient. A simple examination will allow in most
      cases to define the origin of the hair loss and reassure the patient rapidly as
      to its likely evolution if it is reversible. The examination must take into
      account the medical, chirurgical, gynaecological and dietary antecedents and the
      cosmetic habits. These elements must be situated in time and complemented by a
      clinical examination to define the loss as diffuse or localised and in the latter
      case, expose scar damage. The clinical examination will be associated with a
      trichogram and in certain cases with a biopsy or a squam prelevement. Further,
      the blood can be analysed for different metabolically and hormonal elements.
      Finally, the treatments already administered must be known in order to identify
      the beneficial and secondary effects, which will allow the definition of a new
      treatment, if required.

PMID- 15516055
TI  - [The scaly scalp].
AB  - Scaly scalp is a common problem in the pediatric and adult population. The
      possible causes range from the commonly seen tinea capitis, seborrheic dermatitis
      and psoriasis to rare diseases such as lupus erythematosus and lichen planus. In
      all cases a thorough history and physical examination are important first steps
      to successful diagnosis and treatment.

PMID- 15516056
TI  - [Androgenetic alopecia].
AB  - The physiopathology of androgenetic alopecia is linked to the action of the
      androgens of the bulbs pilairs of the scalp. The action of these androgens can be
      associated with the level of hormones in circulation and with the genetic
      predisposition which will influence the activity of these androgens at the
      periphery. The classifications of the evolution of alopecia will be done
      following Norwood for the male and following Ludwig for the female. Hormonal
      investigation will be effectuated on the female only in the case of research on
      or the identification of hyperandrogenia; this is essential in order to direct
      the therapy. The diagnose and the therapeutic follow-up are essentially clinical
      but can be assisted by a trichogram which will show-up the miniaturisation
      process of androgenetic alopecia and the telogen effluvium of the affected areas.
      The treatment of alopecia can be local or general. The local treatment will use a
      lotion of minoxidil 2 to 5% whether the patient is male of female. On males, an
      inhibitor of the 5 alpha reductase 2, finasteride, has shown its efficiency at a
      dose of 1 mg/day. On females oestroprogestatives will be used, if they are not
      counter-advised, associated with an anti-androgen: either cyproterone acetate or
      spironolactone. A therapeutic evaluation will be made after 6 months of
      treatment.

PMID- 15516057
TI  - [Alopecia areata and treatment].
AB  - Alopecia areata is a non scarring inflammatory hair disease, frequently
      recurrent. It commonly presents as round patches of hair loss which can be the
      first manifestation of a more severe alopecia: totalis or universalis. A CD4
      lymphocytic infiltrate surrounds the hair follicle and is presumed to play a role
      in the hair fall. There are many treatments available which may help stimulate
      regrowth. The efficacy, risks, and benefits of each treatment have to be
      considered when choosing a treatment plan.

PMID- 15516058
TI  - [Psychological consequences of chronic hair diseases].
AB  - The author is looking to the psychological consequences of chronic hair diseases
      through a review of the recent literature. In general those consequences are
      depending on the coping skills and on the personality traits. The effect of hair
      loss on the quality of life is similar to that of a severe psoriasis. The most
      important effect is a loss of self-confidence. This is enhanced by an insecure or
      ambivalent attachment pattern. The coping skills will therefore be different and
      less flexibles. Two psychiatric syndromes are first mentioned: the body
      dysmorphic syndrome (very slight or imaginary defect in appearance) and
      trichotillomania. Androgenetic alopecia leads to an important suffering in women
      mostly. Alopecia induced by cancer chemotherapy has been reported to cause
      changes in self-concept and body image. This does not return to the previous
      state after regrowth of hair for a majority of patients. A cosmeto-oncologic care
      strategy is developed in our department to improve the quality of life of the
      patients during this difficult coping period. Alopecia areata has an important
      psychiatric comorbidity: mostly anxiety and depression. Old stressful life events
      are frequently reported at the onset of the disease revealing a chronic stress.
      Those patients have difficulties to express their feelings (what is called
      alexithymia). With a systemic vision this is interpreted as an unconscious task
      of avoiding family conflicts. This conflicts are raising the anxiety of family
      splitting coming from early loss or death in the previous generations. A cautious
      family therapy helps to change those unconscious myths.

PMID- 15516059
TI  - [Prevalence of mental disorders in the family practice].
AB  - The review of the literature shows the high prevalence of mental disorders in the
      family practice and the important role of the general practitioners in the
      detection and the treatment of these diseases.

PMID- 15516060
TI  - [The setting in observation: management in general medicine].
AB  - The law of June 26, 1990 (protection measure of the mental patients) has replaced
      the old law of collocation of 1850 (review in 1873). Conceived in the line of the
      principles of the European Convention of the Humans right, it constitutes an
      important reform of the involuntary treatment of the mental patients and recalls,
      without any doubt, that the patient is prone of right. The article describes the
      scope of application of the law of June 26, 1990, and the methods of initiation
      of a protection measure. Then, the measure in a hospital environment (ordinary
      procedure and urgent procedure), as well as the measure in a family environment
      are approached in their waning. Furthermore, the role of the general practitioner
      is evoked at the various stages of the procedure.

PMID- 15516062
TI  - [Use of antipsychotic drugs in the elderly].
AB  - It is actually well observed that antipsychotic drugs are commonly used in the
      elderly patients. The most important side-effects related to the use of first
      generation antipsychotics are the extrapyramidal side-effects and their
      consequences (increase risk of falls, problems with articulation and speech,
      faster decline in cognition, etc.). Today with the atypical antipsychotics much
      less side-effects are observed but this class of drugs is not without risks. In
      this paper, we propose some recommendations for the use of these medications in
      the elderly population.

PMID- 15516061
TI  - [Use of antipsychotics in first line].
AB  - Today, antipsychotic drugs are widely used in the medical management of various
      psychiatric conditions. Although, the first generation neuroleptics have proved
      their efficacy in treating the positive psychotic symptoms of schizophrenia,
      their use has been associated with a variety of side effects including
      significant extrapyramidal symptoms. The newer antipsychotics offer many notable
      advantages compared with the older neuroleptics. Indeed, they are not only
      effective at treating positive psychotic symptoms but their use has also been
      associated with a positive clinical impact on negative symptoms of schizophrenia
      and their indication has also been extended to the management of bipolar
      disorder. Although, they do present a better side effects profile, some specific
      problems have been reported such as weight gain and increased risk for diabetes.

PMID- 15516063
TI  - [Antidepressants: TCA versus SSRI versus other new agents].
AB  - The medications that appeared in the last two decades, offer praticians a wider
      choice than ever in the treatment of major depressive disorders. The aim of this
      article was first to compare tricyclic antidepressants and serotonine selective
      reuptake inhibitors. It was quite obvious that it was impossible to take no
      account of the birth of newer antidepressants. So we reviewed the efficacy-
      throughout their mechanims of action--of those different antidepressive agents,
      as well as their side-effects. One could think that the coming-out of molecules
      simpler to use, would facilitate the prescription. In fact, it does and it
      doesn't; it allows praticians, more than before, to accord with their clinical
      touch. That means that, at comparable efficacy, we now can choose therapeutic
      agents that fit more adequately a particular patient, his/her characteristics as
      well as his/her somatic and psychiatric history.

PMID- 15516064
TI  - [Obsessive compulsive disorder].
AB  - Obsessive compulsive disorder (OCD) is a disabling psychiatric problem frequently
      encountered, with a chronic, fluctuating course. Several symptomatic categories
      are described, depending on the kind of symptoms displayed and on underlying
      cognitive disturbances and beliefs. OCD has a strong genetic component but
      environmental factors leading to cerebral lesions in the striatum have also been
      implicated. Treatment usually associates medication and behavior therapy. It has
      a favorable impact, most of the time, on the patients' functioning, total
      remission being rather rare.

PMID- 15516065
TI  - [A certificate, a control. For whom? What for? How? Introduction: standards for a
      certificate].

PMID- 15516066
TI  - [Physical violence: what about the certificate?].
AB  - It is of paramount importance to be precise when drawing up a report, in a case
      of aggravated assault. Such precision will serve to give the Judge a better
      conception of the extent of the injuries, the severity of the aggression, and
      thus of the eventual sentence. The extent of the injury must be determined, and
      the exact part of the body clearly stipulated. The general practitioner will be
      able to note the rections of the child standing in front of her. Is he
      frightened? or again his mental attitude? Furthermore, should a boy arrive at his
      surgery, stating that another doctor had refused to receive his family, one
      should be careful. The doctor must consider all the particular aspects of the
      case, and observe the child, speak to him, and endeavour to become his confidant.
      This will be time well spent, and will prove advantageous to the victim.

PMID- 15516067
TI  - [The sportive certificate and...the responsibility!].
AB  - If your patient is an benevolent friendly sportsman (woman), you are able to do
      the sportive certificate. But mind! The responsibility of the physician is
      engaged if he signs without physical examination. The sports with competition and
      sports with danger so as parachutism, dive, alpinism and so on are reserved to
      specialist physician in sports.

PMID- 15516068
TI  - [Medical certificate in sickness and disability insurance area].
AB  - Physicians have to complete medical certificates required by the sickness and
      incapacity insurance in Belgium. Certificate for incapacity for work allows the
      worker to take a rest needed by his health state. It is a part of the medical
      treatment. Incapacity for work is defined differently in the two main social
      legislations in our country: the legal frame concerning employed workers and the
      other one concerning free workers. In both legislations however, it is important
      that practitioners give the useful information to the advisor doctor of the
      insurance sickness fund. Making so, he helps his patient with coping with the
      controls imposed by the law. Using official forms is not compulsory but helps the
      physician to complete correctly an incapacity for work certificate. In health
      care area, certificates are needed to obtain reimbursement of treatments. The
      same concern will guide the practitioner when he completes these certificates.

PMID- 15516069
TI  - [Medical certificates for driving licence, for safety belt].
AB  - Concerning driving licence, there are two groups of medical criteria determined
      by "arrete royal" according to the type of driving licence. In order to be
      declared a qualified driver, the candidate has to fulfil the minimal norms
      determined in the annex 6 of the "arrete royal" of 23 March 1998 concerning
      visual faculty and must be free from any disease or physical abnormality or
      psychological disorders likely to jeopardize the security while driving. For the
      candidates of the first group, only an honor statement is required. If the
      candidate does not know if he plainly fulfils the norms to sign that statement,
      he has to go and see a physician of his own choice. According to the candidate's
      pathology, the doctor may refer him to a specialist. The latter will have one or
      several complementary tests done. According to the medical examinations' result,
      the physician will then make the statement--total ability, partial ability or
      disability--and fill in the form provided to that end. Concerning the exemption
      of the use of safety belt, the "arrete royal" of 13 May 1975, still applicable
      today, does not determine any criterium. The physician is only required to state
      that there is a serious medical contra-indication against the use of safety belt.

PMID- 15516070
TI  - [Report and death certificate].
AB  - The death certificate is a document which must be completed by the medical
      practitioner who examines the deceased person and it could be a valuable
      statistical tool. This approach is to be highly qualified in as much as an
      external examination of the body is often insufficient to make a valid diagnosis.
      The too rare recourse to autopsy--clinical as well as medico-legal--also does not
      provide clarification to these data. We try to highlight some medico-legal
      reflexes essential to good medical practice.

PMID- 15516072
TI  - [Plastic surgery: is it still medicine?].
AB  - Esthetic surgery is today a commercial product. However, it remains a real
      surgical practice with its results but also its complications and the difficulty
      to have the good indication in order to avoid the possible excess dictated by the
      medias.

PMID- 15516071
TI  - [Certificates for insurances: common law, industrial accidents, personal
      insurances].
AB  - The certificates for the insurances are medical testimonies based on this
      principle: the truth, all the truth, nothing but the truth. They must give to the
      insurance the informations which are essential for building the patient's file,
      but they must respect the rules of ethics and the laws concerning the protection
      of privacy and the patient's rights. The certificate giving the description of
      the traumatic lesions is essential in all the procedures but the physician must
      know what to write and to whom this document must be delivered. In common law,
      where the victim must prove the lesions and their traumatic origin, the
      certificate is due to the patient himself. In industrial accidents, the specific
      law of 10 April 1971 dictates the contents of the several certificates: report of
      the lesions, recovery, review. In personal insurance, the law concerning the
      patient's rights teaches the limits of the information and to whom it must be
      given. The certificate is a service and a right of the victim; it must be quite
      relevant.

PMID- 15516073
TI  - [Dermo-cosmetics and prevention of skin aging].
AB  - Skin aging is the result of the addition of intrinsic aging (chronological aging)
      and extrinsic aging induced by environmental factors among whose ultraviolet
      radiation plays a predominant role (actinic aging). The physiopathological
      mechanisms of skin aging are well better known. UV radiations act either directly
      on DNA either through the formation of free radicals. The skin aging is
      characterized by the decline of numerous skin functions. Its clinical
      presentation is accentuated in UV exposed-skin. To struggle against skin aging is
      first of all to prevent it by means of an efficient photoprotection, an adequate
      general life style and preventive treatments as alpha-hydroxyacids, retinoids and
      antioxidants.

PMID- 15516074
TI  - [Hormone therapy of ageing: myths and realities].
AB  - Is well being in the elderly be improved by hormone replacement therapy which
      compensate deficits accounting for generalized weakness, poor endurance, loss of
      muscle strength, impaired mobility and balance and decreased cognitive functions?
      Hormone replacement therapy of menopause has favorable effects on bone loss and
      decreased cognitive functions but also on several unpleasant symptoms--vasomotor
      instability, skin atrophy, mucosal dryness, anxiety and fatigue--but at the prize
      of increased incidence of cancer and cardiovascular morbidity. Decreased
      testosterone levels in elderly men are associated with increased fatigability,
      decreased muscle strength and bone mass and increased risks of accelerated
      atheromatosis. Testosterone substitution seems to be helpful but with side
      effects, particularly development of prostate cancer. Aging also affects adrenal
      function. The consequences of decreased DHEA production are still matter of
      debate. DHEA administration in elderly women seems to be associated with
      favorable effects on physical and psychological well being. Somatopause is
      characterized by a progressive decrease of growth hormone production starting as
      soon as the third decade. Growth hormone therapy has favorable effects on lean
      body mass, skin atrophy as well on body fat reduction. However, numerous side
      effects and the theoretical increased risk of cancer limit the use of growth
      hormone therapy in the elderly.

PMID- 15516075
TI  - [Esthetic dermatology: incidents and accidents].

PMID- 15516076
TI  - [Esthetic surgery, a luxury...but at which price?].
AB  - Esthetic surgery became very popular during the last years. It helps many
      patients psychologically. However, the operations have to correspond to the
      wishes of the patients. Therefore, the patients have not to be only informed of
      the possible results but also of the risk of complications, the presence of
      scars, of swellings, etc. At this condition only will the patients be satisfied
      of their esthetic operation.

PMID- 15516077
TI  - [Which contraception in 2004?].
AB  - The part of the hormonal contraception in Belgium is important. The mode of
      administration has diversified during these last years. Indeed, in order to
      prevent spotting and breakthrough bleeding sometimes associated with low dosage
      pill, trans mucosa as well as trans cutaneous hormone administrations are
      interesting developments. The use of these "non oral" administrations also aim at
      reducing the risk of forgetting the contraceptive pill which is, together with
      the leave of the method for intolerance the major cause of unplanned pregnancies
      in young women.

PMID- 15516078
TI  - [Breast cancer treatment in 2004: towards a tailored approach].
AB  - Breast cancer remains one of the most frequent malignancies that general
      practitioners are confronted with. Given their key-counselling role for the
      affected families, they need regular updates on the multi-disciplinary management
      of the disease. This has been characterized by an evolution towards less
      aggressive surgery, sparing many women the morbidity of a full axillary node
      dissection; in parallel, there is increasing hope for "individualized" adjuvant
      medical treatment, given the development of new technologies that provide an
      "identity card" of the genes expressed by each tumour. These technologies should
      improve our ability to identify which women truly need adjuvant chemotherapy and
      to select the best medical treatment on an individual basis. While providing
      these messages of hope, this chapter also reviews the major classes of drugs used
      for the treatment of advanced breast cancer.

PMID- 15516079
TI  - [The general practitioner facing hepatitis C].
AB  - Infection due to hepatitis C virus is currently a major public health problem,
      worldwide but also in Belgium. Indeed, 200 million people (3% of the world
      population, 1% of the Belgian population) are infected with, in more than 80% of
      the cases, an evolution toward chronic infection with the potential development
      of severe liver disease (chronic hepatitis with fibrosis, cirrhosis,
      hepatocarcinoma). The general practitioner has a central position in the
      management of hepatitis C. His role is to prevent the infection, giving advice on
      the risk factors, to screen high risk groups, to monitor infected patients and to
      discuss with him the indications and contra-indications for antiviral therapy and
      to follow the treated patient in close collaboration wit the
      hepatogastroenterologist to ensure adherence, to manage the side effects and to
      monitor the non treated patient as well as the non responder.

PMID- 15516080
TI  - [Conservative treatment of the painful shoulder. Review of the literature].
AB  - Painful shoulder is due to several diseases. The most frequent presentation is
      the so-called shoulder periarthritis. This entity includes lesions and functional
      disturbances of paraarticular tissues: tendons, ligaments, synovial bursae. The
      review of the studies concerning the treatment is disappointing because a too low
      quality in term of definition of the pathologies studied, heterogeneity of the
      populations and lack of long term evaluations. Anti-inflammatory drugs seem to
      have a poor efficacy. In contrast, the corticosteroids injections are useful,
      with an increase of efficacy when made under control of ultrasonography or
      fluoroscopy. Rehabilitation could be useful but data are too preliminary to
      permit conclusions. Finally, no study was found to help us to evaluate the
      interest of an association of different therapeutical methods.

PMID- 15516082
TI  - Making it all add up.

PMID- 15516083
TI  - Board's eye view.

PMID- 15516084
TI  - Expert witnesses.

PMID- 15516085
TI  - A minor injuries clinic: a year of change, innovation and integrated working.

PMID- 15516086
TI  - Clinical decision making: thinking outside the box.

PMID- 15516087
TI  - Treating and preventing tetanus in A&E.

PMID- 15516088
TI  - Understanding the mechanism of injury and kinetic forces involved in traumatic
      injuries.
AB  - In this article, the author describes the kinetic forces patients can be
      subjected to during traumatic incidents or accidents and how these impact on
      injuries.

PMID- 15516089
TI  - E-learning - new technologies but slow progress?

PMID- 15516090
TI  - DentSim - a future teaching option for dentists.
AB  - Apart from a requirement to acquire more and more academic knowledge, during
      their training, dental students need to acquire a full range of highly precise
      manual and technical skills, including excellent hand/eye coordination, to enable
      them to visualize and understand how to prepare cavities, prior to placing
      restorations. Furthermore, unlike medical students, dental students are in the
      position of administering treatment to patients very early in their training. The
      increasing academic workload means that these skills have to be mastered in a
      short space of time. This you will gain in the future only through the use of
      effective methods of the educations - for example by the use of the computer
      assisted dental simulators (DentSim/DenX), which serves the visual-, audio- and
      practical learning channel simultaneously. Unlike the conventional phantom heads,
      the DentSim-unit has the following advantages - the acquisition of knowledge
      takes place in a multimedia learning environment with a high audio-visual content
      and degree of interaction and complexity, - problem-oriented learning takes place
      through clinically relevant work, - individual students can work to personalized
      programs through the digital tutor function, - two-dimensional knowledge is
      transferred into three-dimensional spatial work, - three-dimensional preparations
      can be easily analysed by two-dimensional error analysis, - all preparation
      exercises are recorded for error and effectiveness analysis. Apart from student
      training, the computer-assisted simulators can also be used for the evaluation of
      the effectiveness or the quality control of various teaching methods in the
      context of Evidence Based Dental Education.

PMID- 15516091
TI  - One year's experience with virtual reality preclinical laboratory simulation at
      the University of Tennessee.
AB  - Virtual reality-based preclinical simulation learning is a new teaching modality
      with significant potential. The University of Tennessee Health Science Center,
      College of Dentistry has completed its first year of student experience using 40
      DentSim simulators, in conjunction with an 80-unit traditional simulation
      laboratory. This article describes this experience and relates both the positive
      and negative aspects as they impacted on the students, staff and school. The
      purpose of the article is to relay information pertinent to this new educational
      modality to other educational institutes interested in pursuing virtual reality
      dental simulation. The results of the first-year experience were encouraging,
      although certain areas proved problematic and frustrating for both students and
      staff.

PMID- 15516092
TI  - Introduction to the published contributions from the "Innovative methods in
      education, further education and training" workshop.

PMID- 15516093
TI  - Trends, current developments, and concepts in distance learning and E-learning.
AB  - A glance at the history of distance learning shows that there is a long tradition
      of using contemporary technical resources for learning and teaching purposes. For
      some, the holy grail of distance learning is the concept of the industrialization
      (mass production) of teaching and learning. Although reality has time and again
      caught up with technological promise, the scope for using new information and
      communication technologies in teaching has frequently been disregarded. In the
      future, learning will entail handling organized knowledge resources in demand
      specific, organized communities formed for finding solutions to distinct problems
      and generating new knowledge about learning processes within the problem solving
      process. The development of the potential of "e-learning" (and actually, it bears
      contemplating whether this term puts too much emphasis on conventional learning
      organized in temporally-limited courses or similar, to the detriment of
      intelligent management of knowledge in its own working context) will depend upon
      the extent to which organizations succeed in promoting the development of a
      learning and working culture, for example, by incentive systems, team promotion,
      and free access to knowledge resources. The Masters degree in Organization
      Studies is presented against this background as an example of teaching using a
      combination of resources, leading to undreamed of learning success.

PMID- 15516094
TI  - Computer-assisted learning in human and dental medicine.
AB  - This article describes the development and application of new didactic methods
      for use in computer-assisted teaching and learning systems for training doctors
      and dentists. Taking the Meducase project as an example, didactic models and
      their technological implementation are explained, together with the limitations
      of imparting knowledge with the "new media". In addition, legal concepts for a
      progressive, pragmatic, and innovative distribution of knowledge to undergraduate
      students are presented. In conclusion, potential and visions for the wide use of
      electronic learning in the German and European universities in the future are
      discussed. Self-directed learning (SDL) is a key component in both undergraduate
      education and lifelong learning for medical practitioners. E-learning can already
      be used to promote SDL at undergraduate level. The Meducase project uses self
      directed, constructive, case- and problem-oriented learning within a learning
      platform for medical and dental students. In the long run, e-learning programs
      can only be successful in education if there is consistent analysis and
      implementation of value-added factors and the development and use of media
      didactic concepts matched to electronic learning. The use of innovative forms of
      licensing - open source licenses for software and similar licenses for content -
      facilitates continuous, free access to these programs for all students and
      teachers. These legal concepts offer the possibility of innovative knowledge
      distribution, quality assurance and standardization across specializations,
      university departments, and possibly even national borders.

PMID- 15516095
TI  - Dentocase - open-source education management system in dentistry.
AB  - Since 2001, an interdisciplinary project on multimedia education in medicine has
      been sponsored by the Federal Ministry of Education and Research at the Charite.
      One part of the project is on dentistry. In the light of the results of a survey
      of dental students, an Internet-based education management system was created
      using open-source back-end systems. It supports four didactic levels for editing
      documentation of patient treatments. Each level corresponds to the learning
      abilities of the students. The patient documentation is organized to simulate the
      working methods of a physician or dentist. The system was tested for the first
      time by students in the summer semester of 2003 and has been used since the
      winter semester of 2003 as part of the curriculum.

PMID- 15516096
TI  - Internet-capable publication database system.
AB  - Scientific databases are generally accessible to the public via the Internet.
      Reports of most peer-reviewed (quotable) research is thus available to
      researchers and others. However, other reports and information of interest to
      researchers and teachers such as poster presentations at congresses, articles
      describing techniques and teaching material, and details of vocational and
      continuing education courses (nonquotable literature) generally do not appear in
      such databases. This nonquotable literature is often of great use to teachers. A
      project was therefore initiated at the Munster Dental Clinic which aimed to
      address the problem by developing a database of all publications and other
      printed material produced by the staff (faculty). After a systematic search, all
      such publications (quotable and nonquotable) were entered in the database which
      is partially accessible via the Internet and fully accessible via the Munster
      Dental Clinic's Intranet. The complete list can be found in the protected
      Intranet areas, which can be accessed by all the Dental Clinic's staff members.
      The database also permits Munster Clinic staff to access the Internet and locate
      those publications that are on the Internet by year of publication and topic.

PMID- 15516097
TI  - PREPassistant: a system for evaluating tooth preparations.
AB  - Learning the widely differing forms of tooth preparation, especially in
      restorative dentistry, places high demands on both trainees and instructors with
      regard to precision, reproducibility, assessment, evaluation and three
      dimensional conceptualization. In the past, evaluation of such preparations has
      been against subjective parameters and their interpretation by the assessor
      (usually the instructor). The use of CAD systems in teaching seminars and courses
      allows an objective assessment of tooth preparations and offers the trainee the
      possibility of measuring him/herself against a standard, of detecting errors, and
      of achieving perfection in the required tasks. The PREPassistant system described
      in this article is one such CAD-assisted learning system. It is recommended both
      for students in dental schools and for the continuing education of established
      dentists. Its strengths are that it produces a design for a tooth preparation,
      enables exact comparison with an ideal preparation, detects errors, and promotes
      improvements and perfection.

PMID- 15516098
TI  - Treatment of a single-tooth gap with a Cerec 3D crown on an implant: A case
      report.
AB  - The present article describes the procedure for inserting a Cerec 3D crown on an
      implant. The current software version R 1503 and the new VITA Mark II TriLuxe
      blocks are used in this case.

PMID- 15516099
TI  - Implementing government policies in clinical practice.

PMID- 15516100
TI  - A clinical study and the national service framework for diabetes.
AB  - Clinical assessment and management for anyone who has diabetes may be influenced
      by the development of the National Service Framework (NSF) for Diabetes. Through
      a case study, this article explains how the NSF for Diabetes and other recent NHS
      documentation has influenced our approach to managing a type 2 diabetic patient
      whose feet are categorised as 'high risk'. Some of the potential shortfalls of
      the NSF for Diabetes are also discussed in this context.

PMID- 15516101
TI  - Policy implementation in practice: the case of national service frameworks in
      general practice.
AB  - National Service Frameworks are an integral part of the government's drive to
      'modernise' the NHS, intended to standardise both clinical care and the design of
      the services used to deliver that clinical care. This article uses evidence from
      qualitative case studies in three general practices to illustrate the
      difficulties associated with the implementation of such top-down guidelines and
      models of service. In these studies it was found that, while there had been
      little explicit activity directed at implementation overall, the National Service
      Framework for coronary heart disease had in general fared better than that for
      older people. Gunn's notion of 'perfect implementation' is used to make sense of
      the findings.

PMID- 15516102
TI  - The role of outcome measures in assessing change in the at-risk rheumatoid foot.
AB  - In common with other outcome measures, those for the at-risk rheumatoid foot need
      to be sensitive, specific and patient focussed, although currently these combined
      features are not available within one measure. There is also the issue of cross
      validation with other commonly used measures to be considered. Both government
      policy and clinical need predicate development of suitable measures for the
      rheumatoid foot. In the first part of this paper, general issues relating to
      outcome measures and some government policy are considered and in the second,
      outcome measures relating to the at-risk rheumatoid foot are introduced alongside
      a discussion on the implications for practitioners.

PMID- 15516103
TI  - The use of qualitative research methodologies to explore leg ulceration.
AB  - Qualitative research is used increasingly within tissue viability and this
      article specifically presents its use within the body of literature on leg
      ulceration. This article offers a discussion of the key features of qualitative
      methodology, such as subjectivity, bracketing, rigour and the analytic process.
      Furthermore it will be shown that understanding the underpinning philosophical
      approach is essential for clinicians undertaking qualitative research. The rich
      data obtained through this approach will be presented, revealing how a person
      living with leg ulceration can be heard.

PMID- 15516104
TI  - Mating behavior 101.

PMID- 15516105
TI  - Don't call me 'four eyes'.

PMID- 15516106
TI  - Cancer/testis antigen expression and autologous humoral immunity to NY-ESO-1 in
      gastric cancer.
AB  - Gastric cancer has the highest mortality rate and the second-highest morbidity
      rate of all malignant tumors in China. Since cancer/testis (CT) antigens are
      expressed in various types of human tumors but generally not in normal tissue
      except for testis, they are promising antigens for cancer immunotherapy. NY-ESO
      1, in particular, is the most immunogenic of the CT antigens. To study the
      feasibility of developing a CT antigen vaccine for gastric cancer, 101 gastric
      cancer samples were analyzed for the presence of NY-ESO-1 mRNA and that of 10
      other CT antigen genes. Twelve out of 101 samples (11.9%) were found to be NY-ESO
      1 mRNA-positive, 11 of them from advanced stage patients. In 7 of the 12 NY-ESO-1
      mRNA-positive samples, the NY-ESO-1 protein was also detected by
      immunohistochemistry. An autologous humoral immune response to NY-ESO-1 was
      detected in 6 of 12 advanced stage NY-ESO-1 mRNA-positive patients, indicating
      that NY-ESO-1 is immunogenic in advanced stage gastric cancer. The serum from a
      patient with an NY-ESO-1 negative but LAGE-1 positive tumor was also found to be
      NY-ESO-1 antibody positive, possibly due to cross-reactivity between NY-ESO-1 and
      LAGE-1. All NY-ESO-1 mRNA-positive gastric cancer samples also expressed one to
      seven additional CT genes, revealing a tendency toward a clustered expression
      pattern, regardless of disease stage. About 74% of the samples expressed at least
      one CT antigen, most frequently MAGE-3 (41.6%). NY-ESO-1 and MAGE-3 are thus
      potential targets for a multivalent CT antigen vaccine.

PMID- 15516107
TI  - Enzymatically amplified surface plasmon resonance imaging method using RNase H
      and RNA microarrays for the ultrasensitive detection of nucleic acids.
AB  - A novel surface enzymatic amplification method that utilizes RNA microarrays in
      conjunction with the enzyme RNase H is developed for the ultrasensitve detection
      and analysis of target DNA molecules. The enzyme RNase H is shown to selectively
      and repeatedly destroy RNA from RNA-DNA heteroduplexes on gold surfaces; when
      used in conjunction with the label-free technique of surface plasmon resonance
      imaging, multiple DNA targets can be detected at a concentration of 10 fM on a
      single chip. In addition, this method is utilized for the sequence-specific
      detection of the TSPY gene in both purified and unpurified PCR products. Finally,
      in a series of kinetics measurements, the initial rate of hydrolysis is shown to
      depend directly on the surface concentration of DNA-RNA heteroduplexes.

PMID- 15516108
TI  - Anion-exchange displacement centrifugal partition chromatography.
AB  - Ion-exchange displacement chromatography has been adapted to centrifugal
      partition chromatography. The use of an ionic liquid, benzalkonium chloride, as a
      strong anion-exchanger has proven to be efficient for the preparative separation
      of phenolic acid regioisomers. Multigram quantities of a mixture of three
      hydroxycinnamic acid isomers were separated using iodide as a displacer. The
      displacement process was characterized by a trapezoidal profile of analyte
      concentration in the eluate with narrow transition zones. By taking advantage of
      the partition rules involved in support-free liquid-liquid chromatography, a
      numerical separation model is proposed as a tool for preliminary process
      validation and further optimization.

PMID- 15516109
TI  - Laser desorption and matrix-assisted laser desorption/ionization mass
      spectrometry of 29-kDa Au:SR cluster compounds.
AB  - Positive and negative ions generated by laser-based ionization methods from three
      gold:thiolate cluster compounds are mass analyzed by time-of-flight mass
      spectrometry. The three compounds have similar inorganic core masses (
      approximately 29 kDa, approximately 145 Au atoms) but different n-alkanethiolate
      ligands associated with each cluster compound (Au:SR, R = butane, hexane,
      dodecane). Irradiation of neat films (laser desorption/ionization) and films
      generated by dilution of the cluster compounds in an organic acid matrix (matrix
      assisted laser desorption/ionization) with a nitrogen laser (337 nm) produced
      distinct ion abundances that are relevant to different structural aspects of the
      cluster compound. Laser desorption/ionization of neat Au:SR compound films
      produces ions consistent with the inorganic core mass (i.e., devoid of original
      hydrocarbon content). Matrix-assisted laser desorption/ionization produces either
      ions with m/z values consistent with the core mass of the cluster compounds or
      ions with m/z values consistent with the approximate molecular weight of the
      cluster compounds, depending on ionization conditions. The ion abundances, and
      ionization conditions under which they are detected, provide insight into
      desorption/ionization processes for these unique cluster compounds as well as
      other analytes typically studied by matrix-assisted laser desorption/ionization.

PMID- 15516110
TI  - 2DCOR-GC: an application of the generalized two-dimensional correlation analysis
      as a route to optimization of continuous flow supercritical fluid reactions.
AB  - A new approach for optimization and monitoring of continuous reactions has been
      developed using 2D correlation methods for the analysis of GC data (2DCOR-GC).
      2DCOR-GC maps are obtained following perturbation of the system that allow the
      effect of changing reaction parameters such as time, temperature, pressure, or
      concentration to be both monitored and sequenced with regard to changes in the
      raw GC data. In this paper, we describe the application of the 2DCOR-GC technique
      to monitoring the reverse water-gas shift reaction in scCO(2). 2DCOR-GC is
      combined with FT-IR data to validate the methodology. We also report the
      application of 2DCOR-GC to probe the mechanism of the alkylation of m-cresol with
      isopropyl alcohol in scCO(2) using Nafion SAC-13 as the catalyst. These results
      identify coeluting peaks that could easily be missed without exhaustive method
      development.

PMID- 15516111
TI  - Magnetic cell separation using antibody binding with protein a expressed on
      bacterial magnetic particles.
AB  - Bacterial magnetic particles (BacMPs) are efficient platforms of proteins for
      surface display systems. In this study, mononuclear cells from peripheral blood
      were separated using BacMPs expressing protein A on the BacMP membrane surface
      (protein A-BacMPs), which were complexed with the Fc fragment of anti-mouse IgG
      antibody. The procedure of positive selection involves incubation of mononuclear
      cells and mouse monoclonal antibodies against different cell surface antigens
      (CD8, CD14, CD19, CD20) prior to treatment with protein A-BacMP binding with
      rabbit anti-mouse IgG secondary antibodies. Flow cytometric analysis showed that
      approximately 97.5 +/- 1.7% of CD19(+) and CD20(+) cells were involved in the
      positive fraction after magnetic separation. The ratio of the negative cells in
      the negative fraction was approximately 97.6 +/-1.4%. This indicates that CD19(+)
      and CD20(+) cells can be efficiently separated from mononuclear cells. Stem cell
      marker (CD34) positive cells were also separated using protein A-BacMP binding
      with antibody. May-Grunwald Giemsa stain showed a high nuclear/cytoplasm ratio,
      which indicates a typical staining pattern of stem cells. The separated cells had
      the capability of colony formation as hematopoietic stem cells. Furthermore, the
      inhibitory effect of magnetic cell separation on CD14(+) cells was evaluated by
      measurement of cytokine in the culture supernatant by ELISA when the cells were
      cultured with or without lipopolysaccharide (LPS). The induction of IL1-beta,
      TNFalpha, and IL6 was observed in the presence of 1 ng/mL LPS in all fractions.
      On the other hand, in the absence of LPS, BacMPs had little immunopotentiation to
      CD14(+) cells as well as that of artificial magnetic particles, although TNFalpha
      and IL6 were slightly induced in the absence of LPS in the positive fraction.

PMID- 15516112
TI  - Resistance, capacitance, and electrode kinetic effects in Fourier-transformed
      large-amplitude sinusoidal voltammetry: emergence of powerful and intuitively
      obvious tools for recognition of patterns of behavior.
AB  - Large-amplitude sinusoidal ac voltammetric techniques, when analyzed in the
      frequency domain using the Fourier transform-inverse Fourier transform sequence,
      produce the expected dc and fundamental harmonic ac responses in addition to very
      substantial second, third, and higher ac harmonics that arise from the presence
      of significant nonlinearity. A full numerical simulation of the process, Red
      right arrow over left arrow Ox + e(-), incorporates terms for the uncompensated
      resistance (R(u)), capacitance of the double layer (C(dl)), and slow electron
      transfer kinetics (in particular, the reversible potential (E degrees ), rate
      constant (k(0)), and charge transfer coefficient (alpha) from the Butler-Volmer
      model). Identification of intuitively obvious patterns of behavior (with
      characteristically different sensitivity regimes) in dc, fundamental, and higher
      harmonic terms enables simple protocols to be developed to estimate R(u), C(dl),
      E degrees , k(0), and alpha. Thus, if large-amplitude sinusoidal cyclic
      voltammograms are obtained for two concentrations of the reduced species, data
      obtained from analysis of the recovered signals provide initial estimates of
      parameters as follows: (a) the dc cyclic component provides an estimate of E
      degrees (because the R(u) and k(0) effects are minimized); (b) the fundamental
      harmonic provides an estimate of C(dl) (because it has a high capacitance-to
      faradaic current ratio); and (c) the second harmonic provides an estimate of
      R(u), k(0), and alpha (because the C(dl) effect is minimized). Methods of
      refining the initial estimates are then implemented. As a check on the fidelity
      of the parameters (estimated on the basis of an essentially heuristic approach
      that solely utilizes the dc, fundamental, and second harmonic voltammograms),
      comparison of the predicted simulated and experimental third (or higher) harmonic
      voltammograms can be made to verify that agreement between theory and experiment
      has been achieved at a predetermined level. The use of the heuristic pattern
      recognition approach to evaluate the oxidation of ferrocene at a platinum
      electrode (a reversible process) in the very high resistance solvent
      dichloromethane (0.1 M Bu(4)NPF(6)) and the reduction of [Fe(CN(6))](3)(-) at a
      glassy carbon electrode (a quasi-reversible process) in much lower resistance but
      higher capacitance conditions found in aqueous (0.5 M KCl) media is described and
      verifies the inherent advantages of employing large-amplitude sinusoidal
      techniques in quantitative studies of electrode processes.

PMID- 15516113
TI  - The nanopore electrode.
AB  - The fabrication and electrochemical characterization of truncated cone-shaped
      nanopore electrodes are reported. A nanopore electrode is a Pt disk electrode
      embedded at the bottom of a conical pore, the circular orifice of the pore having
      nanometer dimensions. The electrochemical properties of nanopore electrodes with
      orifice radii of 39 and 74 nm are presented. Both the steady-state and transient
      voltammetric behavior of the nanopore electrode are reported and compared to
      predictions obtained using finite-element simulations. The truncated cone-shaped
      pore electrode possesses a unique transport property-the steady-state flux of
      molecules into a deep pore is limited by the restriction near the pore orifice,
      and thus, the steady-state current is independent of the pore depth. This
      characteristic is potentially useful in studying transport through nanometer
      scale orifices.

PMID- 15516114
TI  - Manipulation of self-assembled structures of magnetic beads for microfluidic
      mixing and assaying.
AB  - We present an original concept of manipulation of magnetic microbeads in a
      microchannel. It is based on the dynamic motion of a self-assembled structure of
      ferrimagnetic beads that are retained within a microfluidic flow using a local
      alternating magnetic field. The latter induces a rotational motion of the
      magnetic particles, thereby strongly enhancing the fluid perfusion through the
      magnetic structure that behaves as a dynamic random porous medium. The result is
      a very strong particle-liquid interaction that can be controlled by adjusting the
      magnetic field frequency and amplitude, as well as the liquid flow rate, and is
      at the basis of very efficient liquid mixing. The principle is demonstrated using
      a microfluidic chip made of poly(methyl methacrylate) with integrated soft
      ferromagnetic plate structures. The latter are part of an electromagnetic circuit
      and serve to locally apply a magnetic field over the section of the microchannel.
      Starting from a laminar flow pattern of parallel fluorescein dye and
      nonfluorescent liquid streams, we demonstrate a 95% mixing efficiency using a
      mixing length of only 400 microm and at liquid flows of the order of 0.5 cm/s. We
      anticipate that the intense interaction between the fluid and magnetic particles
      with functionalized surfaces holds large potential for the development of future
      bead-based assays.

PMID- 15516115
TI  - Continuous flow microfluidic device for rapid erythrocyte lysis.
AB  - Leukocyte isolation from whole blood to study inflammation requires the removal
      of contaminating erythrocytes. Leukocytes, however, are sensitive to prolonged
      exposure to hyper/hypoosmotic solutions, temperature changes, mechanical
      manipulation, and gradient centrifugation. Even though care is taken to minimize
      leukocyte activation and cell loss during erythrocyte lysis, it is often not
      possible to completely avoid it. Most procedures for removal of contaminating
      erythrocytes from leukocyte preparations are designed for bulk processing of
      blood, where the sample is manipulated for longer periods of time than necessary
      at the single-cell level. Ammonium chloride-mediated lysis is the most commonly
      used method to obtain enriched leukocyte populations but has been shown to cause
      some activation and selective loss of certain cell types. The leukocyte yield and
      subsequent activation status of residual leukocytes after NH(4)Cl-mediated lysis
      have been shown to depend on the time of exposure to the lysis buffer. We have
      developed a microfluidic lysis device that deals with erythrocyte removal at
      nearly the single-cell level. We can achieve complete lysis of erythrocytes and
      approximately 100% recovery of leukocytes where the cells are exposed to an
      isotonic lysis buffer for less than 40 s, after which the leukocytes are
      immediately returned to physiological conditions. Theoretically, this process can
      be made massively parallel to process several milliliterss of whole blood to
      obtain a pure leukocyte population in less than 15 min.

PMID- 15516116
TI  - Reactions and fluidics in miniaturized natural convection systems.
AB  - Buoyancy-driven convection offers a novel and greatly simplified mechanism for
      generating continuous nonpulsatile flow fields and performing thermally activated
      biochemical reactions. In this paper, we build on our previous work by
      constructing a multiwell device incorporating an array of 35-microL cylindrical
      cavities to perform polymerase chain reaction (PCR) amplification of a 191-base
      pair fragment associated with membrane channel proteins M1 and M2 of the
      influenza-A virus in as little as 15 min with performance comparable to
      conventional thermocyclers. We also describe entirely new adaptations of
      convective flows by conducting a series of coordinated flow visualization and
      computational studies to explore the design of closed-loop systems to execute
      tunable thermocycling, pumping, and mixing operations in a format suitable for
      integration into miniaturized biochemical analysis systems. Using 15-microL
      convective flow loops, we are able to perform PCR amplification of the same 191
      base pair fragment associated with the influenza-A virus, as well as a 295-base
      pair segment of the human beta-actin gene in a format offering an enhanced degree
      of control and tunability. These convective flow devices can be further scaled
      down to nanoliter volumes and are ideally suited as a platform for a new
      generation of low-power, portable microfluidic DNA analysis systems.

PMID- 15516117
TI  - Near-simultaneous and real-time detection of multiple analytes in affinity
      microcolumns.
AB  - A miniaturized immunoassay system based on beads in poly(dimethylsiloxane)
      microchannels for analyzing multiple analytes has been developed. The method
      involves real-time detection of soluble molecules binding to receptor-bearing
      microspheres, sequestered in affinity column format inside a microfluidic
      channel. Identification and quantitation of analytes occurs via direct
      fluorescence measurements or fluorescence resonance energy transfer. A
      preliminary account of this work based on single-analyte format has been
      published in this journal (Buranda, T.; Huang, J.; Perez-Luna, V. H.; Schreyer,
      B.; Sklar, L. A.; Lopez, G. P. Anal. Chem. 2002, 74, 1149-1156). We have extended
      the work to a multianalyte model system composed of discrete segments of beads
      that bear distinct receptors. Near-simultaneous and real-time detection of
      diverse analytes is demonstrated. The importance of this work is established in
      the exploration of important factors related to the design, assessment, and
      utility of affinity microcolumn sensors. First, beads derivatized with surface
      chemistry suitable for the attachment of fluorescently labeled biomolecules of
      interest are prepared and characterized in terms of functionality and receptor
      site densities by flow cytometry. Second, calibrated beads are incorporated in
      microfluidic channels. The analytical device that emerges replicates the basic
      elements of affinity chromatography with the advantages of microscale and real
      time direct measurement of bound analyte on beads rather than the indirect
      determination from eluted sample typical of affinity chromatography. In addition,
      the two-compartment analysis of the assay data as demonstrated in single-analyte
      columns provides a template upon which the dynamics of multiple-analyte assays
      can be characterized using existing theoretical models and be tested
      experimentally. The assay can potentially detect subfemtomole quantities of
      protein with high signal-to-noise ratio and a large dynamic range spanning nearly
      4 orders of magnitude in analyte concentration in microliter to submicroliter
      volumes of analyte fluid. The approach has the potential to be generalized to a
      host of bioaffinity assay methods including analysis of protein complexes (e.g.,
      biomolecular indicators of diseases). Proof-of-principle analytes include FLAG
      peptide and carcinoembryonic antigen detected at physiologically relevant
      concentration levels.

PMID- 15516118
TI  - Effect of culture conditions on the achievable taxonomic resolution of Raman
      spectroscopy disclosed by three Bacillus species.
AB  - Confocal micro-Raman spectroscopy requires a minimum of sample handling and no
      reagents and allows fast identification of microorganisms. Since it reflects the
      overall molecular composition of the cells, it provides much more information
      than classical, microbial analyses. However, since the molecular makeup of a cell
      depends on culture conditions, it can be argued that this will affect the
      reproducibility and discrimination ability of Raman spectroscopy. We used
      Bacillus cereus, Bacillus pumilus, and Bacillus licheniformis, which are known to
      be clearly distinct from each other and each displaying important phenotypic
      heterogeneity, in a wide variety of culture conditions to analyze this. It is
      illustrated that the influence of culture conditions on the identification
      accuracy and taxonomic resolution of Raman spectroscopy is important though the
      effect on the final identification is limited within the set of stains studied.
      Furthermore, some conditions even allow for better discrimination than others.
      From a practical point of view, it is especially important that differences in
      culturing time (and culturing temperature) can be accommodated.

PMID- 15516119
TI  - Simultaneously monitoring gene expression kinetics and genetic noise in single
      cells by optical well arrays.
AB  - An optical fiber based well array platform was used for simultaneous, dynamic
      gene expression monitoring from hundreds of individual live Escherichia coli
      cells carrying promoter-fluorescent reporter gene fusions. High information
      content about gene expression kinetics and cell-to-cell gene expression
      variability can be collected from a single experiment. These data are invaluable
      for investigating gene regulation and gene networks as well as for systems
      biology applications.

PMID- 15516120
TI  - Myoglobin immunoassay utilizing directional surface plasmon-coupled emission.
AB  - We described an immunoassay for the cardiac marker myoglobin on a thin silver
      mirror surface using surface plasmon-coupled emission (SPCE). SPCE occurs for
      fluorophores in proximity (within approximately 200 nm) of a thin metal film (in
      our case, silver) and results in a highly directional radiation through a glass
      substrate at a well-defined angle from the normal axis. We used the effect of
      SPCE to develop a myoglobin immunoassay on the silver mirror surface deposited on
      a glass substrate. Binding of the labeled anti-myoglobin antibodies led to the
      enhanced fluorescence emission at a specific angle of 72 degrees . The
      directional and enhanced directional fluorescence emission enables detection of
      myoglobin over a wide range of concentrations from subnormal to the elevated
      level of this cardiac marker. Utilizing SPCE allowed us also to demonstrate
      significant background suppression (from serum or whole blood) in the myoglobin
      immunoassay. We expect SPCE to become a powerful technique for performing
      immunoassays for many biomarkers in surface-bound assays.

PMID- 15516121
TI  - Preparative linear ion trap mass spectrometer for separation and collection of
      purified proteins and peptides in arrays using ion soft landing.
AB  - A preparative mass spectrometer for microarray fabrication is reported. The
      instrument includes an atmospheric pressure ionization source, a linear ion trap
      mass analyzer, an ion collection surface positioning system, and a surface
      loading chamber with independent vacuum pumping. It was designed for the
      production of protein arrays using the ion soft-landing technique to collect ions
      on a surface after separation by mass/charge ratio. Small microarrays have been
      prepared by isolating and soft landing individual protein or peptide ions after
      electrospray ionization of mixtures. The composition and purity of the separated
      materials has been confirmed using independent external mass spectrometric
      analysis of rinse solutions of the collected spots, either by the new method of
      electrosonic spray ionization MS or by nanospray ionization MS. The ability to
      retain bioactivity in the mass-selected and collected biomolecules has been
      demonstrated in particular cases. The reported instrument has also been
      characterized as an analytical mass spectrometer.

PMID- 15516122
TI  - A low-makeup beveled tip capillary electrophoresis /electrospray ionization mass
      spectrometry interface for micellar electrokinetic chromatography and nonvolatile
      buffer capillary electrophoresis.
AB  - A robust interface has been developed for interfacing micellar electrokinetic
      chromatography (MEKC) and nonvolatile buffer capillary electrophoresis (CE) to
      electrospray ionization mass spectrometry (ESI-MS). The interface consists of two
      parallel capillaries for separation (50 microm i.d. x 155 microm o.d.) and makeup
      (50 microm i.d. x 155 microm o.d.) housed within a larger capillary (530 microm
      i.d. x 690 microm o.d.). The capillaries terminate in a single tapered tip having
      a beveled edge. The use of a tapered beveled edge results in a greater tip
      orifice diameter (75 microm) than in a previous design from our laboratory (25
      microm) that used a flat tip. While maintaining a similar optimum flow rate and
      consequently similar sample dilution, a 75-microm beveled emitter is more rugged
      than a 25-microm flat tip. Furthermore, the incorporation of a sheath liquid
      capillary allows the compositions of the final spray solution to be controlled.
      The application of this novel CE/ESI-MS interface was demonstrated for MEKC using
      mixtures of triazines (positive ion mode) and phenols (negative ion mode). The
      ability to perform CE/ESI-MS using a nonvolatile buffer was demonstrated by the
      analysis of gangliosides with a buffer consisting of 40 mM borate and 20 mM alpha
      cyclodextrin.

PMID- 15516123
TI  - Measurement of selected polybrominated diphenyl ethers, polybrominated and
      polychlorinated biphenyls, and organochlorine pesticides in human serum and milk
      using comprehensive two-dimensional gas chromatography isotope dilution time-of
      flight mass spectrometry.
AB  - A new method using comprehensive two-dimensional gas chromatography and isotope
      dilution time-of-flight mass spectrometry (GCxGC-IDTOFMS) for the simultaneous
      measurement of selected polychlorinated biphenyls (PCBs), organochlorine
      pesticides (OCPs), and brominated flame retardants is presented. In contrast to
      the reference methods based on classical GC/MS, a single injection of the extract
      containing all compounds of interest results in accurate identification and
      quantification. Using GCxGC ensures the chromatographic separation of most
      compounds, and TOFMS allows mass spectral deconvolution of coeluting compounds as
      well as the use of (13)C-labeled internal standards for quantification. Isotope
      ratio measurements of the most intense ions for both native and labels ensure the
      required specificity. The use of this new method with an automated sample
      preparation procedure developed at the Centers for Disease Control and Prevention
      (CDC) for the analysis of human serum and milk compared favorably to conventional
      isotope-dilution one-dimensional gas chromatography-high-resolution mass
      spectrometry (GC-IDHRMS) for the different human serum and milk pools tested. The
      instrumental detection limits ranged between 0.5 pg/microL and 10 pg/microL and
      the method detection limits ranged between 1 and 15 pg/microL (N = 59 analytes).
      The reproducibility of the method was almost as good as with GC-IDHRMS, the
      relative standard deviations ranging between 1 and 11% for OCPs measured in human
      serum. OCP, PBDE, and PCB levels measured using the two methods were highly
      correlated, and the deviations between the two methods were below 20% for most
      analytes with concentrations above 1 ng/g milk lipids.

PMID- 15516124
TI  - All-optical hydrogen-sensing materials based on tailored palladium alloy thin
      films.
AB  - Optical reflectance measurements were performed to determine the hydrogen
      response characteristics of 20-nm-thick Pd-Au (Ag) films. The response
      characteristics displayed a strong dependence on alpha, mixed alpha/beta, and
      beta Pd-hydride phases formed in the films. The response time peaks in the alpha 
      -> beta phase transition region (1625 s at 0.4% H(2) for Pd(0.94)Ag(0.06) and 405
      s at 1% H(2) for Pd(0.94)Au(0.06)), consistent with critical slowing down
      phenomena. The alpha --> beta phase transition region was shifted and inhibited
      by changing the alloy element to Au and increasing its corresponding content to
      40 atom %, respectively. Initial hydrogen uptake rate measurements determined
      that, due to the adsorption of ambient background gases, the rate-limiting step
      for alpha or beta phase PdH formation is dissociative chemisorption of hydrogen
      for each palladium alloy film. By tuning the alloy content and composition of the
      palladium films, the surface properties of the film become more receptive toward
      the rapid detection of hydrogen and a novel hydrogen-sensing material using Pd
      alloyed with 40 atom % Au is presented.

PMID- 15516125
TI  - A potentiometric and 113Cd NMR study of cadmium complexation by natural organic
      matter at two different magnetic field strengths.
AB  - The binding of cadmium to Suwannee River natural organic matter (NOM) has been
      investigated across a broad range of Cd/C ratios (0.00056-0.0056) and pH values
      (3.5-11) by (113)Cd NMR spectroscopy at two magnetic field strengths (B(0) = 9.4
      and 11.7 T). Caused by the very peculiar and highly complex nature of the Cd-NOM
      exchanging system, these (113)Cd NMR spectra are characterized by a pH- and
      concentration-dependent superposition of slow, intermediate, and fast chemical
      exchange. The complex interplay of solution chemistry and chemical exchange
      requires a thorough mapping of this Cd-NOM chemically exchanging system through
      NMR acquisition at two magnetic field strengths and a systematic variation of
      Cd/C ratios and pH values. The interpretation of (113)Cd NMR spectra is greatly
      facilitated and constrained by simultaneous measurements of pH and pCd, which
      allows a model-independent calculation of organically bound Cd(2+) under all
      experimental conditions. Within the range of chemical conditions applied in this
      study, (113)Cd NMR spectrometric evidence is consistent with coordination of
      cadmium by oxygen, nitrogen, and sulfur ligands in NOM. Under all experimental
      conditions, cadmium is primarily coordinated to oxygen; however, several lines of
      evidence point to the participation of nitrogen ligands, even in acidic solutions
      where nitrogen ligands are primarily bound to protons. Under alkaline conditions,
      up to one-third of cadmium may be coordinated to nitrogen, and a small, but
      unquantifiable, percentage of cadmium is coordinated to sulfur ligands, as
      evidenced by far-low-field (113)Cd NMR resonances.

PMID- 15516126
TI  - Role of hydroboron intermediates in the mechanism of chemical vapor generation in
      strongly acidic media.
AB  - Unknown and controversial aspects related to the mechanisms of hydrolysis of
      borane complexes and to the mechanisms of chemical vapor generation for trace
      element determination in strongly acidic media (0.01-10 M HCl) have been
      investigated and clarified. The overall hydrolysis rates of borane complexes
      (BH(4)(-), H(3)N-BH(3)) in the acidity range of 0.2-10 M HCl were several orders
      of magnitude lower than those predicted by kinetics laws and obtained in the pH
      range of 3.8-14. The decomposition of the borane complexes takes place stepwise
      and proceeds through the formation of hydroboron intermediates, L(x)()BH(4)(
      )(x)()(n)() (x = 1, 2, 3), where L could be one or more species among the donor
      groups H(2)O, NH(3), OH(-), and Cl(-) and n is the charge of the hydroboron
      species (n = 0, +1, -1, depending on L). Some intermediates present surprisingly
      long lifetimes at elevated acidities and play a key role in determining both the
      overall hydrolysis rates of borane complexes and the reactivity of Hg(II),
      As(III), Sb(III), Bi(III), Se(IV), Te(IV), and Sn(IV) in chemical vapor
      generation for trace element determination. Atomic absorption experiments
      demonstrated that almost all trihydroboron species (LBH(3)(n)()), dihydroboron
      species (L(2)BH(2)(n)()), and monohydroboron species (L(3)BH(n)()) play an active
      role in the generation of elemental mercury and stibine. Some of these
      intermediates are inactive or play a marginal role in the generation of arsine,
      bismuthine, and hydrogen selenide. Hydrogen telluride is preferentially formed by
      those hydroboron species, which are stable in strongly acidic conditions, while
      the same species are unreactive in the generation of stannane. The collected
      experimental evidence is in agreement with the general reactivity of the elements
      in chemical vapor generation techniques and, together with other literature data,
      definitely rule out the hypothesis of "nascent hydrogen" as a possible mechanism
      of chemical vapor generation by borane complex derivatization.

PMID- 15516127
TI  - On-line determination of the intracellular poly(beta-hydroxybutyric acid) content
      in transformed Escherichia coli and glucose during PHB production using stopped
      flow attenuated total reflection FT-IR spectrometry.
AB  - An automated approach for rapid on-line monitoring of the solid and liquid phases
      present in bioprocesses based on mid-IR Fourier transform spectrometry is
      introduced. The principles of this new approach are presented using the example
      of the quantitative and qualitative analysis of poly(beta-hydroxybutyric acid)
      (PHB) accumulated in living bacterial cells as well as dissolved glucose during
      two 27-h fermentation processes. FT-IR spectra were recorded on-line using a
      diamond-attenuated total reflection (ATR) cell connected to the fermentation
      broth by means of a computer-controlled flow system. For calibration of the FT-IR
      method, standard reference analysis procedures for PHB (gas chromatography) and
      glucose (HPLC) were used. While pumping the fermentation broth through the flow
      cell, the recorded spectra corresponded to the fermentation solution, which
      allowed the determination of glucose in a range from 3.8 to -10.3 g/L. Upon
      stopping the flow, the cells settled on the ATR surface, and the thus recorded
      spectra enabled the determination of the intracellular PHB content of Escherichia
      coli in a range from 0.005 to 0.766 g/L. Errors of cross-validation of 0.264 g/L
      for glucose and 0.037 g/L for PHB were obtained. Application of one PLS
      calibration model to another fermentation was possible with prediction errors of
      0.493 g/L for glucose and 0.105 g/L for PHB. Furthermore, from the position and
      shape of the PHB carbonyl band, it could be concluded that the PHB granules
      inside the E. coli are predominantly amorphous.

PMID- 15516128
TI  - A kinetic method for HO2*/O2*- determination in advanced oxidation processes.
AB  - A new kinetic method is developed for the determination of hydroperoxyl radical
      (HO(2)(*))/superoxide radical (O(2)(*)(-)) in aqueous solution, and the
      calibration using a kinetic half-life technique is also established for
      determining the concentration of HO(2)(*)/O(2)(*)(-) as produced in the
      UV/H(2)O(2) process. This new method is based on the reduction of Fe(3+)-EDTA
      into Fe(2+)-EDTA by HO(2)(*)/O(2)(*)(-) and the well-known Fenton-like reaction
      of H(2)O(2) and Fe(2+)-EDTA to yield the hydroxyl radicals (OH(*)). Benzoic acid
      scavenges the OH radicals to produce hydroxybenzoic acids, which are analyzed by
      fluorescence detection (lambda(ex) = 320 nm; lambda(em) = 400 nm). The limit of
      detection for the new method depends on the pH values, and it is determined as
      3.22 x 10(-)(11) M with signal-to-noise ratio of 2 at pH 5. In addition, the
      present technique has the advantage of using inexpensive and easily available
      nonenzymatic reagents that do not require the specific instrument and chemicals
      and of being insensitive to the moderate concentration of possible interferences
      often found in aqueous phase.

PMID- 15516129
TI  - Information-dependent acquisition-mediated LC-MS/MS screening procedure with
      semiquantitative potential.
AB  - The development of a LC-MS/MS general unknown screening procedure for
      toxicologically relevant substances in blood samples by means of information
      dependent acquisition on a Q-TOF is reported. IDA is an artificial intelligence
      based product ion scan mode providing automatic "on-the-fly" MS to MS/MS
      switching. By performing information-dependent scanning at two different
      fragmentation energies, two collision-induced dissociation product ion spectra
      for each of the detected compounds are generated. As such, information-rich MS/MS
      spectra are obtained from precursor ions not known beforehand. In addition,
      limitation of the MS/MS acquisition time to an acceptable minimum resulted in an
      almost instantaneous switch back to the MS mode. As such, this approach provided
      MS chromatograms that still could be of use for semiquantitative purposes. Since
      the switching intensity threshold, unequivocally related to the background noise,
      proved a critical parameter, the solid-phase extraction procedure, the liquid
      chromatographic conditions, and the mass spectrometric parameters all were
      optimized to the advantage of information-dependent acquisition. Finally, the
      screening procedure we developed was benchmarked, on one hand, qualitatively
      against the results obtained from traditional GUS approaches in a number of
      routine toxicological laboratories (20 samples) and, on the other hand,
      quantitatively with respect to its potential against established LC-MS/MS methods
      (7 samples). The procedure performed very well from a qualitative point of view;
      almost all of the drugs detected by the conventional techniques were identified,
      as well as additional drugs that were not previously reported. The procedure
      proved well-suited for an initial semiquantitative assessment, as is customary
      in, for example, forensic toxicology before accurate intoxication levels are
      determined using targeted analytical analyses.

PMID- 15516130
TI  - De novo peptide sequencing based on a divide-and-conquer algorithm and peptide
      tandem spectrum simulation.
AB  - Mass spectrometry-based de novo peptide sequencing is generally more reliable on
      high-resolution instruments owing to their high resolution and mass accuracy. On
      a lower resolution instrument such as the more widely used quadrupole ion traps,
      de novo peptide sequencing is not so reliable or requires more MS(3) experiments.
      However, the peptide CID spectrum has been demonstrated to be quite reproducible
      on an ion trap instrument and can be predicted with good accuracy. A new de novo
      peptide sequencing technique, DACSIM, combining a divide-and-conquer algorithm
      for deriving sequence candidates and spectrum simulation for sequence refinement,
      is developed for spectra acquired on an ion trap instrument. When DACSIM was used
      to sequence peptides 500-1900 u in mass generated from proteolytic digests of
      hemoglobin and myoglobin, the success rate was 70% with a false positive rate of
      only 6%, when isoleucine and leucine residues were not distinguished.

PMID- 15516131
TI  - On-line technique for the determination of the delta37Cl of inorganic and total
      organic Cl in environmental samples.
AB  - Here we describe an on-line method for measuring delta(37)Cl values of chloride
      bearing salts, waters, and organic materials using multicollector continuous-flow
      isotope ratio mass spectrometry (CF-IRMS). Pure AgCl quantitatively derived from
      total Cl in water, inorganic Cl salts, and biological samples was reacted with
      iodomethane in evacuated 10-mL stopper sealed glass vials to produce methyl
      chloride gas. A GV Instruments Multicollector CF-IRMS with CH(3)Cl optimized
      collector geometry was modified to accommodate a headspace single-sample gas
      injection port prior to a GC column. The GC column was a 2-m Porapak-Q packed
      column held at 160 degrees C. The resolved sample CH(3)Cl was introduced to the
      IRMS source in a helium stream via an open split. delta(37)Cl values were
      calculated by measurement of CH(3)Cl at m/z 52/50 and by comparison to a
      reference pulse of CH(3)Cl calibrated to standard mean ocean chloride. Sample
      CH(3)Cl analysis time was approximately 6 min. Injections of 40 microL of pure
      CH(3)Cl gas yielded a repeatability (+/-SD) of +/-0.06 per thousand for
      delta(37)Cl (n = 10). Combined GC and IRMS source linearity for CH(3)Cl was <0.2
      per thousand/nA (V) peak height. External repeatability, based on processing of
      seawater and NaCl reference solutions, was better than +/-0.08 per thousand. The
      smallest sample for delta(37)Cl analysis by this method was approximately 0.2
      micromol of Cl. Selected results from a river basin and biological samples study
      illustrate the potential of on-line chlorine isotope assays in environmental
      pollution studies.

PMID- 15516132
TI  - Dual microelectrodes for distance control and detection of nitric oxide from
      endothelial cells by means of scanning electrochemical microscope.
AB  - Dual Pt disk microelectrodes consisting of a 10-microm distance sensor and a 50
      microm nitric oxide sensor were prepared. The 50-microm electrode was modified
      with Ni(4-N-tetramethyl)pyridyl porphyrin enclosed in the polymer network of a
      negatively charged electrodeposition paint. This paint prevented the dissolution
      of the otherwise soluble porphyrin in the aqueous test medium due to charge
      interactions. It also denied negatively charged ions in the analyte solution
      access to the electrode surface by electrostatic repulsion, thereby preventing
      interference from anions such as nitrite, nitrate, and ascorbate. With the aid of
      a scanning electrochemical microscope, it was possible to use the distance sensor
      by recording the negative feedback effect on the reduction of molecular oxygen to
      "guide" the nitric oxide sensor to various known distances from a layer of
      adherently growing human umbilical vein endothelial cells for the detection of
      nitric oxide released from the cells upon stimulation with bradykinin. The use of
      the distance sensor made it possible to preserve the integrity of the adherently
      growing cells concomitantly with the modified electrode by preventing the
      deterioration of the modifying layer during the distance adjustment step.

PMID- 15516133
TI  - Comparison of the conductivity properties of the tetrabutylammonium salt of
      tetrakis(pentafluorophenyl)borate anion with those of traditional supporting
      electrolyte anions in nonaqueous solvents.
AB  - Cyclic voltammetry experiments at minielectrodes exhibit less ohmic error for
      lower polarity solvents when the supporting electrolyte anion is
      [B(C(6)F(5))(4)](-) rather than one of the smaller traditional anions such as
      [BF(4)](-), [PF(6)](-), or [ClO(4)](-). Conductance measurements have been
      performed for [NBu(4)][B(C(6)F(5))(4)] in tetrahydrofuran, dichloromethane,
      benzotrifluoride, and acetonitrile and compared with results for [NBu(4)](+)
      salts of several traditional anions in the same solvents. In solvents with
      dielectric constants of 10 or less, ion association constants, K(A), are as much
      as 2 orders of magnitude lower with [B(C(6)F(5))(4)](-), TFAB, as the electrolyte
      anion and the degree of this lowering is related to the acceptor property of the
      solvent. Analyses carried out on the basis of a Fuoss model attribute this fact
      to differences in concentrations of contact ion pairs rather than of solvent
      separated ion pairs. The greater dissociation of the TFAB ion is attributed to
      its highly delocalized charge.

PMID- 15516134
TI  - Dynamic diffusion model for tracing the real-time potential response of polymeric
      membrane ion-selective electrodes.
AB  - A numerical solution for the prediction of the time-dependent potential response
      of a polymeric-based ion-selective electrode (ISE) is presented. The model
      addresses short- and middle-term potential drifts that are dependent on changes
      in concentration gradients in the aqueous sample and organic membrane phase. This
      work has important implications for the understanding of the real-time response
      behavior of potentiometric sensors with low detection limits and with
      nonclassical super-Nernstian response slopes. As a model system, the initial
      exposure of membranes containing the well-examined silver ionophore O,O' '-bis[2
      (methylthio)ethyl]-tert-butylcalix[4]arene was monitored, and the large observed
      potential drifts were compared to theoretical predictions. The model is based on
      an approximate solution of the diffusion equation for both aqueous and organic
      diffusion layers using a numerical scheme (finite difference in time and finite
      elements in space). The model may be evaluated on the basis of experimentally
      available parameters and gives time-dependent information previously inaccessible
      with a simpler steady-state diffusion model. For the cases studied, the model
      gave a very good correlation with experimental data, albeit with lower than
      expected diffusion coefficients for the organic phase. This model may address
      numerous open questions regarding the response time and memory effects of low
      detection-limit ion-selective electrodes and for other membrane electrodes where
      ion fluxes are relevant.

PMID- 15516135
TI  - Factors affecting the potentiometric response of all-solid-state solvent
      polymeric membrane calcium-selective electrode for low-level measurements.
AB  - An all-solid-state calcium-selective electrode was constructed with poly(pyrrole)
      solid-contact doped with calcium complexing ligand Tiron. The potentiometric
      response of this sensor can have a linear range down to 10(-)(9) M with a slope
      close to Nernstian and detection limit equal to 10(-)(9.6). The effects of pH and
      the activity of the interfering ion in the conditioning solution on the
      potentiometric behavior of the constructed sensors were examined. Potential
      stability, reproducibility, and impedance studies were performed. The selectivity
      of the constructed electrode is better than that of the conventional calcium
      selective electrode with internal filling solution of 10(-)(2) M CaCl(2) and
      comparable to that of the best liquid-contact electrodes.

PMID- 15516136
TI  - Microfluidic separation and gateable fraction collection for mass-limited
      samples.
AB  - Integrating multiple analytical processes into microfluidic devices is an
      important research area required for a variety of microchip-based analyses. A
      microfluidic system is described that achieves preparative separations by
      intelligent fraction collection of attomole quantities of sample. The device
      consists of a main microfluidic channel used to perform electrophoresis, which is
      interconnected at 90 degrees to two vertically displaced channels via a
      nanocapillary array membrane. The membrane interconnect contains nanometer
      diameter pores that provide fluidic communication between the channels. Sample
      injection and analyte collection are controlled by application of an electrical
      bias between the microfluidic channels across the nanocapillary array. After the
      separation, the automated transfer of the FITC-labeled Arg, Gln, and Gly bands
      occurs; a fluorescence detector located at the separation/collection channel
      interconnect is used to generate a triggering signal that initiates suitable
      voltages to allow near-quantitative transfer of analyte from the separation
      channel to the second fluidic layer. The ability to achieve such sample
      manipulations from mass-limited samples enables a variety of postseparation
      processing events.

PMID- 15516137
TI  - Stable microstructured network for protein patterning on a plastic microfluidic
      channel: strategy and characterization of on-chip enzyme microreactors.
AB  - Chemical modification of a poly(methyl methacrylate) (PMMA) microchannel surface
      has been explored to functionalize microfluidic chip systems. A craft copolymer
      was designed and synthesized to introduce the silane functional groups onto the
      plastic surface first. Furthermore, it has been found that, through a silicon
      oxygen-silicon bridge that formed by tethering to these functional groups, a
      stable patterning network of gel matrix could be achieved. Thus, anchorage of
      proteins could be realized onto the hydrophobic PMMA microchannels with
      bioactivity preserved as far as possible. The protein homogeneous patterning in a
      microfluidic channel has been demonstrated by performing microchip capillary
      electrophoresis with laser-induced fluorescence detection and confocal
      fluorescence microscopy. To investigate the bioactivity of enzymes entrapped
      within stable silica gel-derived microchannels, the suggested scheme was employed
      to the construction of immobilized enzyme microreactor-on-a-chip. The proteolytic
      activity of immobilized trypsin has been demonstrated with the digestion of
      cytochrome c and bovine serum albumin at a fast flow rate of 4.0 microL/min,
      which affords the short residence time less than 5 s. The digestion products were
      characterized using MALDI-TOF MS with sequence coverage of 75 and 31% observed,
      respectively. This research exhibited a simple but effective strategy of plastic
      microchip surface modification for protein immobilization in biological and
      proteomic research.

PMID- 15516138
TI  - On-chip nanoliter-volume multiplex TaqMan polymerase chain reaction from a single
      copy based on counting fluorescence released microchambers.
AB  - A novel method for multiplex TaqMan PCR in nanoliter volumes on a highly
      integrated silicon microchamber array is described. Three different gene targets,
      related to beta-actin, sex-determining region Y (SRY), and Rhesus D (RhD) were
      amplified and detected simultaneously on the same chip by using three different
      types of human genomic DNA as the templates. The lack of cross-contamination and
      carryover was shown using alternate dispensing of mineral oil-coated
      microchambers containing template and those without template. To confirm the
      specificity of our system to beta-actin, SRY, and RhD genes, we employed the
      larger volume PCR samples to a commercial real-time PCR system, SmartCycler. The
      samples were cycled with the same sustaining temperatures as with the
      microchamber array. Instead of the conventional method of DNA quantification,
      counting the number of the fluorescence released microchambers in consequence to
      TaqMan PCR was employed to our chip. This simple method of observing the end
      point signal had provided a dynamic quantitative range. Stochastic amplification
      of 0.4 copies/reaction chamber was achieved. The microfabricated PCR chip
      demonstrated a rapid and highly sensitive response for simultaneous multiple
      target detection, which is a promising step toward the development of a fully
      integrated device for the "lab-on-a-chip" DNA analysis.

PMID- 15516139
TI  - On-line coupling of microdialysis sampling with microchip-based capillary
      electrophoresis.
AB  - Microdialysis sampling is a technique that has been used for in vivo and in vitro
      monitoring of compounds of pharmaceutical, biomedical, and environmental
      interest. The coupling of a commercially available microdialysis probe to a
      microchip-based capillary electrophoresis (CE) system is described. A
      continuously flowing dialysate stream from a microdialysis probe was introduced
      into the microchip, and discrete injections were achieved using a valveless
      gating approach. The effect of the applied voltage and microdialysis flow rate on
      device performance was investigated. It was found that the peak area varied
      linearly with the applied voltage. Higher voltages led to lower peak response but
      faster separations. Perfusion flow rates of 0.8 and 1.0 microL/min were found to
      provide optimal performance. The on-line microdialysis/microchip CE system was
      used to monitor the hydrolysis of fluorescein mono-beta-d-galactopyranoside (FMG)
      by beta-d-galactosidase. A decrease of the FMG substrate with an increase in the
      fluorescein product was observed. The temporal resolution of the device, which is
      dependent on the CE separation time, was 30 s. To the best of our knowledge, this
      is the first reported coupling of a microdialysis sampling probe to a microchip
      capillary electrophoresis device.

PMID- 15516140
TI  - Micromixing with linked chains of paramagnetic particles.
AB  - Paramagnetic colloidal particles aggregate into linear chains under an applied
      external magnetic field. These particles can be chemically linked to create
      chains that can be magnetically actuated to manipulate microscopic fluid flow.
      The flexibility of the chain can be adjusted by varying the length of the linker
      molecule. In this paper, we describe the use of a suspension of linked
      paramagnetic chains in a rotating magnetic field to perform microscale mixing.
      The effect of chain rotation and flexibility on the diffusion of molecules is
      studied by observing the mixing of an acid and base in a microchannel. We show
      that, as the chain rotation frequency increases, there is marked increase in the
      effective mixing between fluid streams; however, a maximum frequency exists and
      above this frequency the chains are no longer effective in mixing. More flexible
      chains are more effective at mixing over a larger range of frequencies.

PMID- 15516141
TI  - Porous polymer monolith assisted electrospray.
AB  - Coupling low-flow analytical separation instrumentation such as capillary
      electrophoresis, capillary electrochromatography, nano-HPLC, and microfluidic
      based devices with electrospray ionization mass spectrometry has yielded powerful
      analytical tools. However, conventional coupling methodologies such as nanospray
      suffer from limitations including poor conductive coating robustness, constant
      clogging, complicated fabrication processes, and incompatibility with large flow
      rate regimes. This study demonstrates that robust nanospray emitters can be
      fabricated through the formation and utilization of a porous polymer monolith
      (PPM) at the end of a fused-silica capillary. Stable electrosprays can be
      produced from capillaries (75-100-microm i.d.) at a variety of flow rates (50
      1000 nL/min) without the need to taper the capillaries by etching or pulling. The
      PPM is photopatterned to be present only near the capillary exit aperture using
      conditions that generate pore sizes similar to those seen with nanospray tips.
      The porous nature of the PPM aids in developing a stable electrospray generating
      a single clearly visible Taylor cone at relatively high flow rates while at low
      flow rates (<100 nL/min) a mist, presumably from multiple small Taylor cones,
      develops. The hydrophobic nature of the PPM should limit problems with band
      broadening associated with droplet spreading at the capillary exit, while the
      multiple flow paths inherent in the PPM minimize clogging problems associated
      with conventional nanospray emitters. Total ion current traces for a constant
      infusion of standard PPG and cytochrome c solutions are very stable with
      deviations ranging from only 3 to 8%. The PPM-assisted electrospray produces mass
      spectra with excellent signal-to-noise ratios from only a few femtomoles of
      material.

PMID- 15516142
TI  - Surface plasmon resonance near-infrared spectroscopy.
AB  - Near-infrared (NIR) spectroscopy is ill-suited to microanalysis because of its
      low absorptivity. We have developed a highly sensitive detection method for NIR
      spectroscopy based on absorption-sensitive surface plasmon resonance (SPR). The
      newly named SPR-NIR spectroscopy, which may open the way for NIR spectroscopy in
      microanalysis and surface science, is realized by an attachment of the
      Kretschmann configuration equipped with a mechanism for fine angular adjustment
      of incident light. The angular sweep of incident light enables us to make a
      tuning of a SPR peak for an absorption band of sample medium. From the
      dependences of wavelength, incident angle, and thickness of a gold film on the
      intensity of the SPR peak, it has been found that the absorbance can be enhanced
      by approximately 100 times compared with the absorbance obtained without the gold
      film under optimum conditions. This article reports the details of the
      experimental setup and the characteristics of absorption-sensitive SPR in the NIR
      region, together with some experimental results obtained by using it.

PMID- 15516143
TI  - Entrapment of highly active membrane-bound receptors in macroporous Sol-Gel
      derived silica.
AB  - The immobilization of membrane-associated proteins remains a challenging task.
      Herein, we report on the entrapment of two classes of membrane-bound receptors
      into sol-gel derived silica. Both nicotinic acetylcholine receptor (nAChR), a
      ligand-gated ion channel, and dopamine D(2Short) receptor (D2R), a G-protein
      coupled receptor, were entrapped into a series of sol-gel derived nanocomposite
      materials. In cases where the silica had a bimodal pore size distribution wherein
      both mesopores and macropores were present, the two receptors showed 40-80% of
      solution activity over periods of at least 1 month. Furthermore, the dissociation
      constants of entrapped nAChR and D2R for binding to known agonists and
      antagonists were very close to the values obtained for free receptors in
      solution. These results indicate that membrane-bound receptors entrapped into
      bimodal meso/macroporous silica should provide a useful platform for the
      development of bioanalytical devices such as bioaffinity columns or microarrays,
      which could aid in diagnosis and high-throughput drug screening.

PMID- 15516144
TI  - Infrared spectroscopy for chemically specific sensing in silicon-based
      microreactors.
AB  - Fourier transform infrared (FT-IR) spectroscopy in a multiple internal reflection
      (MIR) geometry is integrated with silicon-based microreactors to allow detection
      of a wide range of chemical species while taking advantage of inexpensive batch
      fabrication techniques applicable to silicon substrates. The microreactors are
      fabricated in silicon and glass using standard microfabrication and selective
      etching techniques. The small ( approximately 1 cm side) reactor size provides
      access to nearly the full mid-IR frequency region with MIR-FT-IR, allowing us to
      probe both solution-phase and surface-bound chemical transformations. The wide
      applicability of this approach is demonstrated with two representative test
      cases: kinetics of acid-catalyzed ethyl acetate hydrolysis and amidization of
      surface-tethered amine groups.

PMID- 15516145
TI  - Coupling thin-layer chromatography with vibrational cooling matrix-assisted laser
      desorption/ionization Fourier transform mass spectrometry for the analysis of
      ganglioside mixtures.
AB  - Thin-layer chromatography (TLC), which is widely used for separation of
      glycolipids, oligosaccharides, lipids, and compounds of environmental and
      pharmaceutical interest, can be readily coupled to matrix-assisted laser
      desorption/ionization (MALDI) time-of-flight mass spectrometers, but this
      arrangement usually compromises mass spectral resolution due to the irregularity
      of the TLC surface. However, TLC can be coupled to an external ion source MALDI
      Fourier transform (FT) MS instrument without compromising mass accuracy and
      resolution of the spectra. Furthermore, when the FTMS has a vibrationally cooled
      MALDI ion source, fragile glycolipids can be desorbed from TLC plates without
      fragmentation, even to the point that desorption of intact molecules from
      "hot"matrixes such as alpha-cyano-4-hydroxycinnamic acid is possible. In this
      work, whole brain gangliosides are separated using TLC; the TLC plates are
      attached directly to the MALDI target, where the gangliosides are desorbed,
      ionized, and detected in the FTMS with >70 000 resolving power.

PMID- 15516146
TI  - Correlation of mass spectrometry identified bacterial biomarkers from a fielded
      pyrolysis-gas chromatography-ion mobility spectrometry biodetector with the
      microbiological gram stain classification scheme.
AB  - A pyrolysis-gas chromatography-ion mobility spectrometry (Py-GC-IMS) briefcase
      system has been shown to detect and classify deliberately released bioaerosols in
      outdoor field scenarios. The bioaerosols included Gram-positive and Gram-negative
      bacteria, MS-2 coliphage virus, and ovalbumin protein species. However, the
      origin and structural identities of the pyrolysate peaks in the GC-IMS data
      space, their microbiological information content, and taxonomic importance with
      respect to biodetection have not been determined. The present work interrogates
      the identities of the peaks by inserting a time-of-flight mass spectrometry
      system in parallel with the IMS detector through a Tee connection in the GC
      module. Biological substances producing ion mobility peaks from the pyrolysis of
      microorganisms were identified by their GC retention time, matching of their
      electron ionization mass spectra with authentic standards, and the National
      Institutes for Standards and Technology mass spectral database. Strong signals
      from 2-pyridinecarboxamide were identified in Bacillus samples including Bacillus
      anthracis, and its origin was traced to the cell wall peptidoglycan
      macromolecule. 3-Hydroxymyristic acid is a component of lipopolysaccharides in
      the cell walls of Gram-negative organisms. The Gram-negative Escherichia coli
      organism showed significant amounts of 3-hydroxymyristic acid derivatives and
      degradation products in Py-GC-MS analyses. Some of the fatty acid derivatives
      were observed in very low abundance in the ion mobility spectra, and the higher
      boiling lipid species were absent. Evidence is presented that the Py-GC-ambient
      temperature and pressure-IMS system generates and detects bacterial biochemical
      information that can serve as components of a biological classification scheme
      directly correlated to the Gram stain reaction in microorganism taxonomy.

PMID- 15516147
TI  - Sol-gel-derived ceramic-carbon nanotube nanocomposite electrodes: tunable
      electrode dimension and potential electrochemical applications.
AB  - Nanocomposite electrodes made of sol-gel-derived ceramic-carbon nanotube are
      fabricated by doping mutliwalled carbon nanotubes (MWNTs) into a silicate gel
      matrix. The electrochemical behavior and potential electrochemical applications
      of the ceramic-carbon nanotube nanocomposite electrodes (CCNNEs) are also
      studied. The as-prepared CCNNEs exhibit a tunable dimension ranging from
      conventional electrode to nanoelectrode ensemble (NEE), depending on the amount
      of the MWNT dispersed in the silica sol and finally doped within the gel matrix.
      A high content of the MWNT (i.e., higher than 1.5 mg/mL in the sol) leads to the
      formation of the CCNNE characteristic of an electrode of conventional dimension,
      while a low content (typically lower than 0.10 mg/mL) essentially yields the
      CCNNE like a nanoelectrode ensemble. The NEE is demonstrated to possess good
      electrocatalytic activity toward the oxidation of ascorbic acid (AA), and the
      CCNNE of conventional dimension is found to possess remarkable electrocatalytic
      activity toward the oxidation of glutathione (both reduced and oxidized forms,
      GSH and GSSG). These properties of the CCNNEs essentially offer a new
      electrochemical approach for the detection of AA, GSH, and GSSG. The possible
      essence of the tailor-made dimensions of the CCNNEs is also presented and
      discussed.

PMID- 15516148
TI  - An etched porous interface for on-line capillary electrophoresis-based two
      dimensional separation system.
AB  - The construction and evaluation of an on-column etched fused-silica porous
      junction for on-line coupling of capillary isoelectric focusing (CIEF) with
      capillary zone electrophoresis (CZE) are described. Where two separation columns
      were integrated on a single piece of fused-silica capillary through the etched
      approximately 4 to 5-mm length porous junction along the capillary. The junction
      is easily prepared by etching a short section of the capillary wall with HF after
      removing the polyimide coating. The etched section becomes a porous glass
      membrane that allows only small ions related to the background electrolyte to
      pass through when high voltage is applied across the separation capillary. The
      primary advantages of this novel porous junction interface over previous designs
      (in which the interface is usually formed by fracturing the capillary followed by
      connecting the two capillaries with a section of microdialysis hollow fiber
      membrane) are no dead volume, simplicity, and ruggedness, which is particularly
      well suited for an on-line coupling capillary electrophoresis-based multiple
      dimensional separation system. The performance of the 2D CIEF-CZE system
      constructed by such an etched porous junction was evaluated by the analyses of
      protein mixtures.

PMID- 15516149
TI  - Selective and sensitive fluorescent sensors for metal ions based on manipulation
      of side-chain compositions of poly(p-phenyleneethynylene)s.
AB  - The syntheses and metal-responsive properties of poly(p-phenyleenethynylene)s
      with grafted new pseudo-crown-ether groups are reported. These polymers exhibit
      high sensitivities to alkali ions because of their collective optical properties,
      which are very sensitive to ion-induced conformational changes. The quenching of
      polymer fluorescence caused by the conformational changes is proportional to the
      ion concentration. The selectivity of the sensing materials toward Li(+) ions is
      significantly enhanced by controlling the size of the binding site via
      manipulation of the polymer side-chain compositions. The polymers are very stable
      for their six-month solid-state storage at room temperature.

PMID- 15516150
TI  - Durability and rapidity of response to anakinra in patients with rheumatoid
      arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic and progressive inflammatory disease that
      ultimately leads to disability and functional decline. Because patients usually
      develop RA in mid-life, they may experience its consequences for 20-30 years or
      longer. Proinflammatory cytokines, notably interleukin (IL)-1 and tumour necrosis
      factor-alpha, are believed to play significant pathophysiological roles. Clinical
      trials of biologicals that block these cytokines confirm their
      importance.Anakinra, a recombinant human IL-1 receptor antagonist, improves
      clinical signs and symptoms, and slows radiographic progression in patients with
      active RA. In clinical trials, patients receiving anakinra doses >1 mg/kg,
      whether administered alone or in combination with methotrexate, were two to three
      times more likely than patients receiving placebo to achieve a sustained ACR20
      (American College of Rheumatology criteria) response. Notably, bone erosion slows
      to a greater extent and shows accelerated benefit when anakinra treatment is
      continued for periods beyond 24 weeks. Anakinra has a rapid onset of action, with
      substantial improvements in biochemical indices (C-reactive protein) seen within
      1 week and clinical responses (ACR20 or joint counts) seen within 4 weeks of
      starting treatment. Anakinra is generally well tolerated, with injection site
      reactions being the most common adverse event. These reactions are generally mild
      and typically resolve within 2-3 weeks of treatment. The anakinra product
      labelling does include a warning regarding an increased risk of infections of 2%
      in anakinra-treated patients versus <1% in patients receiving placebo.

PMID- 15516151
TI  - Medication overuse headache from antimigraine therapy: clinical features,
      pathogenesis and management.
AB  - Medication overuse headache (MOH) is being recognised more often in headache,
      neurology and primary care clinics, but is still frequently overlooked. The most
      significant factor in the development of MOH is the lack of widespread awareness
      and understanding on the part of clinicians and patients. While the diagnosis of
      MOH may be suspected clinically, it can only be confirmed in retrospect.
      Diagnosis may take > or =3 months because of the need for prolonged observation
      after cessation of medication. Diagnosis must be based on observation of patterns
      of headaches and medication use, remembering that MOH is only seen in patients
      with migraine and not in those without. MOH should be viewed as an entity that is
      caused or propagated by frequently used medication taken for headache symptomatic
      relief. Because of easy availability and low expense, the greatest problem
      appears to be associated with barbiturate-containing combination analgesics and
      over-the-counter caffeine-containing combination analgesics. Even though triptan
      overuse headache is not encountered with great frequency, all triptans should be
      considered potential inducers of MOH. There are several different theories
      regarding the aetiology of MOH, including: (i) central sensitisation from
      repetitive activation of nociceptive pathways; (ii) a direct effect of the
      medication on the capacity of the brain to inhibit pain; (iii) a decrease in
      blood serotonin due to repetitive medication administration with attendant
      upregulation of serotonin receptors; (iv) cellular adaptation in the brain; and
      (v) changes in the periaqueductal grey matter. The principal approach to
      management of MOH is built around cessation of overused medication. Without
      discontinuation of the offending medication, improvement is almost impossible to
      attain. A three-step approach to treating patients with analgesic rebound
      headaches includes: (i) a bridging or transition programme; (ii)
      nonpharmacological measures; and (iii) prophylactic medication started early in
      the course of treatment (after offending medication is successfully
      discontinued). The best management advice is to raise awareness and strive for
      prevention. Prophylactic medications should be initiated for patients having > or
      =2 headache days per week. Anticipatory medication use should be discouraged and
      migraine-specific therapy should be considered as early as possible in the
      natural history of patients' headaches. Reduction in headache risk factors should
      include behavioural modification approaches to headache control earlier in the
      natural history of migraine.

PMID- 15516154
TI  - Duloxetine: in stress urinary incontinence.
AB  - Duloxetine is an orally administered, balanced, dual serotonin and norepinephrine
      (noradrenaline) reuptake inhibitor that increases neural input to the urethral
      sphincter, thereby relieving the symptoms of stress urinary incontinence (SUI).
      Duloxetine 40 mg twice daily for 12 weeks reduced the median incontinence episode
      frequency (IEF) to a significantly greater extent than placebo in women with
      predominant symptoms of SUI. In most studies, Incontinence Quality of Life (I
      QOL) questionnaire total scores were significantly improved compared with
      placebo. In a dose-escalation study in women with severe SUI scheduled for
      continence surgery, duloxetine 80-120 mg/day for 8 weeks significantly reduced
      IEF and increased I-QOL total scores compared with placebo, and caused 20% of
      recipients to reconsider their willingness to undergo surgery. Duloxetine or
      duloxetine plus pelvic floor muscle training (PFMT) were more effective in
      reducing the median IEF than PFMT alone or no treatment in women with SUI. Mean I
      QOL total scores suggested that combination therapy was more effective than
      either therapy alone. Nausea was the most frequent adverse event and was the main
      cause for discontinuing duloxetine therapy.

PMID- 15516152
TI  - Chronic urticaria: aetiology, management and current and future treatment
      options.
AB  - Chronic urticaria is a common condition that can be very disabling when severe. A
      cause for chronic idiopathic urticaria (CIU) is only infrequently identified.
      Potential causes include reactions to food and drugs, infections (rarely) and,
      apart from an increased incidence of thyroid disease, uncomplicated urticaria is
      not usually associated with underlying systemic disease or malignancy. About one
      third of patients with CIU have circulating functional autoantibodies against the
      high affinity IgE receptor or against IgE, although it is not known why such
      antibodies are produced, or how the presence of such antibodies alters the course
      of the disease or response to treatment. There are only a few publications
      relating to childhood urticaria, but it is probably similar to the adult form,
      except that adult urticaria is more common. The diagnosis is based on patient
      history and it is vital to spend time documenting this in detail. Extensive
      laboratory tests are not required in the vast majority of patients. Chronic
      urticaria resolves spontaneously in 30-55% of patients within 5 years, but it can
      persist for many years. Treatment is aimed firstly at avoiding underlying
      causative or exacerbating factors. Histamine H1 receptor antagonists remain the
      mainstay of oral treatment for all forms of urticaria. The newer low-sedating
      antihistamines desloratadine, fexofenadine, levocetirizine and mizolastine should
      be tried first. Sedating antihistamines have more adverse effects but are useful
      if symptoms are causing sleep disturbance. Low-dose dopexin is effective and
      especially suitable for patients with associated depression. There is controversy
      as to whether the addition of an histamine H2 receptor antagonist or a
      leukotriene antagonist is helpful. For CIU, second-line agents include
      ciclosporin (cyclosporine) [which is effective in approximately 75% of patients],
      short courses of oral corticosteroids, intravenous immunoglobulins and
      plasmapheresis, although the last two were found to be beneficial in small trials
      only. Treatments for CIU with only limited or anecdotal supportive evidence
      include sulphasalazine, methotrexate, stanazol, rofecoxib and cyclophosphamide.
      The efficacy of photo(chemo)therapy is controversial. Physical urticarias may
      respond to H1 receptor antagonists, although in delayed pressure urticaria, and
      cold, solar and aquagenic urticaria, the response may be disappointing. Second
      line agents for physical urticarias vary depending on the urticaria and most have
      limited supportive evidence. The potential for spontaneous resolution, the
      variation in the disease activity and the unpredictable nature of the disease
      makes the efficacy of treatments difficult to assess.

PMID- 15516157
TI  - Insulin detemir: a review of its use in the management of type 1 and 2 diabetes
      mellitus.
AB  - Insulin detemir (Levemir) is a soluble long-acting human insulin analogue
      acylated with a 14-carbon fatty acid. The fatty acid modification allows insulin
      detemir to reversibly bind to albumin, thereby providing slow absorption and a
      prolonged and consistent metabolic effect of up to 24 hours in patients with type
      1 or type 2 diabetes mellitus. Insulin detemir has a more predictable, protracted
      and consistent effect on blood glucose than neutral protamine Hagedorn (NPH)
      insulin, with less intrapatient variability in glycaemic control, compared with
      NPH insulin or insulin glargine. Insulin detemir, administered once or twice
      daily, is at least as effective as NPH insulin in maintaining overall glycaemic
      control, with a similar or lower risk of hypoglycaemia, especially nocturnal
      hypoglycaemia, compared with NPH insulin in patients with type 1 or type 2
      diabetes. Insulin detemir also provides the added clinical benefit of no
      appreciable bodyweight gain in patients with type 1 diabetes and less bodyweight
      gain than NPH insulin in patients with type 2 diabetes. Insulin detemir is,
      therefore, a promising new option for basal insulin therapy in patients with type
      1 or 2 diabetes.

PMID- 15516153
TI  - Prevention of type 2 diabetes mellitus through inhibition of the Renin
      Angiotensin system.
AB  - Type 2 diabetes mellitus is becoming a major health problem associated with
      excess morbidity and mortality. As the prevalence of type 2 diabetes is rapidly
      increasing, prevention of the disease should be considered as a key objective in
      the near future. Besides lifestyle changes, various pharmacological treatments
      have proven their efficacy in placebo-controlled clinical trials, including
      antidiabetic drugs such as metformin, acarbose and troglitazone, or antiobesity
      agents such as orlistat. Arterial hypertension, a clinical entity in which
      insulin resistance is common, is strongly associated with type 2 diabetes and may
      precede the disease by several years. While antihypertensive agents such as
      diuretics or beta-adrenoceptor antagonists may worsen insulin resistance and
      impair glucose tolerance, newer antihypertensive agents exert neutral or even
      slightly positive metabolic effects. Numerous clinical trials have investigated
      the effects of ACE inhibitors or angiotensin II receptor antagonists (ARAs) on
      insulin sensitivity in hypertensive patients, with or without diabetes, with no
      consistent results. Almost half of the studies with ACE inhibitors in
      hypertensive nondiabetic individuals demonstrated a slight but significant
      increase in insulin sensitivity as assessed by insulin-stimulated glucose
      disposal during a euglycaemic hyperinsulinaemic clamp, while the other half
      failed to reveal any significant change. The effects of ARAs on insulin
      sensitivity are neutral in most studies. Mechanisms of improvement of glucose
      tolerance and insulin sensitivity through the inhibition of the renin-angiotensin
      system (RAS) are complex. They may include improvement of blood flow and
      microcirculation in skeletal muscles and, thereby, enhancement of insulin and
      glucose delivery to the insulin-sensitive tissues, facilitating insulin
      signalling at the cellular level and improvement of insulin secretion by the beta
      cells. Six recent large-scale clinical studies reported a remarkably consistent
      reduction in the incidence of type 2 diabetes in hypertensive patients treated
      with either ACE inhibitors or ARAs for 3-6 years, compared with a thiazide
      diuretic, beta-adrenoceptor antagonist, the calcium channel antagonist amlodipine
      or even placebo. The relative risk reduction averaged 14% (p = 0.034) in the
      CAPPP (Captopril Prevention Project) with captopril compared with a thiazide or
      beta1-adrenoceptor antagonist, 34% (p < 0.001) in the HOPE (Heart Outcomes
      Prevention Evaluation) study with ramipril compared with placebo, 30% (p < 0.001)
      in the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart
      Attack Trial) with lisinopril compared with chlortalidone, 25% (p < 0.001) in the
      LIFE (Losartan Intervention For Endpoint reduction in hypertension study) with
      losartan compared with atenolol, and 25% (p = 0.09) in the SCOPE (Study on
      Cognition and Prognosis in the Elderly) with candesartan cilexetil compared with
      placebo, and 23% (p < 0.0001) in the VALUE (Valsartan Antihypertensive Long-term
      Use Evaluation) trial with valsartan compared with amlodipine. All these studies
      considered the development of diabetes as a secondary endpoint, except the HOPE
      trial where it was a post hoc analysis. These encouraging observations led to the
      initiation of two large, prospective, placebo-controlled randomised clinical
      trials whose primary outcome is the prevention of type 2 diabetes: the DREAM
      (Diabetes REduction Approaches with ramipril and rosiglitazone Medications) trial
      with the ACE inhibitor ramipril and the NAVIGATOR (Nateglinide And Valsartan in
      Impaired Glucose Tolerance Outcomes Research) trial with the ARA valsartan.
      Finally, ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril
      Global Endpoint Trial) will also investigate as a secondary endpoint whether it
      is possible to prevent the development of type 2 diabetes by blocking the RAS
      with either an ACE inhibitor or an ARA or a combination of both. Thus, the recent
      consistent observations of a 14-34% reduction of the development of diabetes in
      hypertensive patients receiving ACE inhibitors or ARAs are exciting. From a
      theoretical point of view, they emphasise that there are many aspects of the
      pathogenesis, prevention and treatment of type 2 diabetes that still need to be
      uncovered. From a practical point of view, they may offer a new strategy to
      reduce the ongoing epidemic and burden of type 2 diabetes.

PMID- 15516158
TI  - Cefditoren pivoxil: a review of its use in the treatment of bacterial infections.
AB  - Cefditoren pivoxil (Spectracef, Meiact) is a third-generation oral cephalosporin
      with a broad spectrum of activity against pathogens, including both Gram-positive
      and -negative bacteria, and is stable to hydrolysis by many common beta
      lactamases. Cefditoren pivoxil is approved for use in the treatment of acute
      exacerbations of chronic bronchitis (AECB), mild-to-moderate community-acquired
      pneumonia (CAP), acute maxillary sinusitis, acute pharyngitis/tonsillitis and
      uncomplicated skin and skin structure infections (indications may differ between
      countries). In clinical trials in adults and adolescents, cefditoren pivoxil
      demonstrated good clinical and bacteriological efficacy in AECB, CAP, acute
      maxillary sinusitis, acute pharyngitis/tonsillitis and uncomplicated skin and
      skin structure infections and was generally well tolerated. Thus, cefditoren
      pivoxil is a good option for the treatment of adult and adolescent patients with
      specific respiratory tract or skin infections, particularly if there is concern
      about Streptococcus pneumoniae with decreased susceptibility to penicillin, or
      beta-lactamase-mediated resistance among the common community-acquired pathogens.

PMID- 15516159
TI  - Seesaw modification of the lateral orbital wall in Le Fort III osteotomy.
AB  - OBJECTIVE: The traditional treatment for patients with syndromic craniosynostosis
      and midfacial retrusion has consisted of Le Fort III osteotomy and advancement.
      Distraction with rigid external systems allows advancement of the midface segment
      much more than the conventional methods. This excessive advancement resulted in
      the superiormost margin of the advancement segment becoming prominent. It can be
      felt easily with palpation and may influence the appearance of the patient
      negatively. This article presents a procedure osteotomy designed to modify the
      osteotomy lines at the lateral orbital rims and smooth the step deformity at the
      lateral canthal region. RESULTS: The seesaw osteotomy produced a smooth contour
      at the lateral orbital rim. Planned advancement was achieved without difficulty
      and without adverse long-term effects.

PMID- 15516160
TI  - Magnetic resonance imaging of the levator veli palatini muscle before and after
      primary palatoplasty.
AB  - OBJECTIVE: To explore the application of magnetic resonance imaging (MRI) in the
      evaluation of patients with cleft palate before and after primary palatoplasty
      with particular attention focused on the levator veli palatini muscle. DESIGN:
      Prospective study using MRIs of subjects before and after primary cleft palate
      surgery. SETTING: Hospital and university based. PATIENTS: One female infant with
      normal anatomy. Three male and four female infants with cleft palate of varying
      severity. INTERVENTION: Furlow double-opposing Z-plasty and V-Y palatoplasty.
      MAIN OUTCOME MEASURES: Magnetic resonance images. RESULTS: It was found that the
      levator veli palatini muscle can be imaged before and after palatal surgery in
      infants using MRI. The muscle may have sufficient volume, proportionate to a
      normal infant or adult, in infants born with cleft palate. If retrodisplaced
      properly, the muscle is likely to be steeper (more vertical) from its origin at
      the base of the skull to its insertion into the velum following palatoplasty,
      thus providing a more favorable angle for elevating the velum. Following palatal
      surgery, the levator muscle mass may not be as cohesive across the velar midline,
      compared with normal musculature. CONCLUSION: MRI is a viable imaging modality
      for the evaluation of the anatomy of the levator veli palatini muscle before and
      after primary palatoplasty in infants born with cleft palate.

PMID- 15516161
TI  - Three-dimensional facial characteristics of Caucasian infants without cleft and
      correlation with body measurements.
AB  - OBJECTIVE: The aim of this study was to characterize the soft tissue facial
      features of infants without cleft and to report on the correlation between these
      with weight, length, and head circumference. DESIGN: This was a prospective study
      using a noninvasive three-dimensional (3D) stereophotogrammetry (C3D) system to
      capture the images of the participants. Landmarks were identified on the 3D
      facial images. Means and SDs were derived for facial distances and angles. A
      facial asymmetry score was calculated for each image. Two sample Student's t
      tests, Pearson's correlation coefficients and analysis of covariance were used to
      ascertain any gender differences and determine whether these could be explained
      by weight differences. PARTICIPANTS: Eighty-three infants, 41 boys and 42 girls,
      were captured at rest with their lips apart, at approximately 3 months of age.
      RESULTS: Significant sex differences, of 1 to 2 mm, were found in several facial
      dimensions, such as face height and nose width. The larger facial measurements
      correlated significantly with body measurements. Analysis of variance confirmed
      these differences could be explained by differences in weight. There were no sex
      differences in the nose/mouth width ratios or in any of the angles measured,
      suggesting that there may be little sex difference in shape. A slight degree of
      asymmetry in the faces of infants without cleft was detected. CONCLUSIONS:
      Comparisons between noncleft controls and infants with cleft should take
      cognizance of normal age and sex variations in height and weight that occur among
      infants.

PMID- 15516162
TI  - Does repairing a cleft lip neonatally have any effect on the longer-term
      attractiveness of the repair?
AB  - OBJECTIVE: To determine whether attractiveness and success of surgical outcome
      differ according to the timing of cleft lip repair. DESIGN: Three experiments
      were conducted: (1) surgeons rated postoperative medical photographs of infants
      having either neonatal or 3-month lip repair; (2) lay panelists rated the same
      photographs; (3) lay panelists rated dynamic video displays of the infants made
      at 12 months. Normal comparison infants were also rated. The order of stimuli was
      randomized, and panelists were blind to timing of lip repair and the purposes of
      the study. SETTING: Four U.K. regional centers for cleft lip and palate.
      PARTICIPANTS: Infants with isolated clefts of the lip, with and without palate.
      INTERVENTION: Early lip repair was conducted at median age 4 days (interquartile
      range [IQR] = 4), and late repair at 104 days (IQR = 57). MAIN OUTCOME MEASURES:
      Ratings of surgical outcome (Experiment 1 only) and attractiveness (all
      experiments) on 5-point Likert scales. RESULTS: In Experiment 1 success of
      surgical outcome was comparable for early and late repair groups (difference = 
      0.08; 95% confidence interval [CI] = -0.43 to 0.28; p = .66). In all three
      experiments, attractiveness ratings were comparable for the two groups.
      Differences were, respectively, 0.10 (95% CI = -2.3 to 0.44, p = .54); -0.11 (95%
      CI = -0.42 to -0.19, p = .54); and 0.08 (95% CI = -0.11 to 0.28, p = .41). Normal
      infants were rated more attractive than index infants (difference = 0.38; 95% CI
      = 0.24 to 0.52; p < .001). CONCLUSION: Neonatal repair for cleft of the lip
      confers no advantage over repair at 3 months in terms of perceived infant
      attractiveness or success of surgical outcome.

PMID- 15516163
TI  - Cleft lip and palate in Jordan: birth prevalence rate.
AB  - OBJECTIVE AND DESIGN: A retrospective investigation was conducted to determine
      the prevalence rate of Jordanian children born with oral clefts from 1991 to
      2001. SETTING: Hospital surgical records from two main sources were used to
      identify all children born with orofacial clefting. Information about date of
      birth, sex, cleft types, and associated major anomalies and syndromes were
      recorded. RESULTS: The overall prevalence rate for live births with cleft lip,
      cleft palate, or both was 1.39 per 1000 live births. Thirty percent of the clefts
      identified affected the lip, 22 percent affected the palate, and 48 percent
      involved the clefts of the lip and palate. In general, higher prevalence rates
      were found for boys than girls (55% boys versus 45% girls). There was a
      statistically significant sex difference between the cleft types. Clefts of the
      isolated palate, however, were more common in girls. Eighteen percent of patients
      with cleft were associated with major anomalies or syndromes. CONCLUSIONS: The
      reported prevalence rate for orofacial clefts among Jordanians is similar to the
      previously reported prevalence rate in white Caucasians. Results and future
      recommendations are discussed.

PMID- 15516164
TI  - Predisposing factors to formation of cleft lip and palate: inherited craniofacial
      skeletal morphology.
AB  - OBJECTIVE: To identify inherited craniofacial morphologic features in individuals
      at high risk for cleft of the lip, cleft palate, or both. SUBJECTS: Twins without
      cleft from 33 pairs of monozygotic twins discordant for cleft lip, cleft palate,
      or both were studied. There were 17 males and 16 females of Caucasian origin,
      ranging from 3 to 18 years (15 with cleft lip and palate [CLP], 10 with cleft lip
      [CL], and 8 with cleft palate [CP]), collected from five craniofacial centers
      (United States and Canada). DESIGN: The twin without cleft (noncleft) from each
      set was compared with an age- and sex-matched control individual from the
      Burlington Growth Centre, Toronto, Ontario. Posteroanterior and lateral
      cephalograms were traced and digitized using a computer custom analysis.
      Descriptive statistics, Student's t tests, and analysis of variance were used to
      test 40 variables in a pilot study comparing the noncleft twin groups with the
      controls. Preliminary analysis permitted pooling of the CLP and CL groups (n =
      25). To minimize false-positive significance, only 14 variables (from the
      maxillofacial area) were tested. RESULTS: Using the raw probabilities, eight
      variables showed significant differences between the pooled noncleft CLP and CL
      (CL[P]) twin group and the controls. However, when the level of significance was
      adjusted, only four (nasal width [p < .01], cranial base length [p < .05],
      cranial base width/length ratio [p < .001], and maxillary width/length ratio [p <
      .05]) were significantly different. No significant differences were confirmed
      between the noncleft CP twin group and the controls. CONCLUSIONS: The noncleft
      member of a discordant monozygotic pair has a number of facial characteristics
      that differ from the general population. These may predispose to the formation of
      a cleft lip or palate and may result from a deficiency or distortion of the
      mesenchyme that forms the craniofacial structures.

PMID- 15516165
TI  - Descriptive epidemiology of oral clefts in a multiethnic population, Hawaii, 1986
      2000.
AB  - OBJECTIVE: To describe the relationship between oral clefts and demographic and
      clinical factors in Hawaii. METHODS: Data were obtained from a birth defects
      registry and included all infants and fetuses with oral clefts delivered during
      1986 through 2000. Subjects were categorized as total, isolated, and nonisolated
      cleft lip with or without cleft palate (CL+/-P) or cleft palate without cleft lip
      (CP). RESULTS: There were 352 total subjects of CL+/-P and 192 total subjects of
      CP with corresponding rates per 10,000 live births of 12.5 for CL+/-P and 6.8 for
      CP. Total, isolated, and nonisolated CL+/-P rates demonstrated no clear pattern
      by maternal age. The total and nonisolated CP rates tended to be higher among
      older maternal age groups. The total CL+/-P rate was higher among Far East
      Asians, Pacific Islanders, and Filipinos than among whites. The total CP rate was
      higher among Far East Asians and Pacific Islanders than among whites, whereas the
      rate for Filipinos was lower than for whites. The total CL+/-P rate was
      substantially lower among females (rate ratio 0.62, 95% confidence interval [CI]
      = 0.49 to 0.77) and the total CP rate substantially higher among females (rate
      ratio 1.52, 95% CI = 1.13 to 2.06). Both CL+/-P and CP were more common with
      lower birth weight and gestational age among the total, isolated, and nonisolated
      groups. CONCLUSIONS: Oral cleft risk was associated with maternal race/ethnicity,
      sex, birth weight, and gestational age. Although some of the observed
      associations were consistent with the literature, others were not.

PMID- 15516166
TI  - The prevalence of caries in children with a cleft lip and/or palate in Southern
      Vietnam.
AB  - OBJECTIVE: The aim of this study was to investigate the prevalence of caries in
      South Vietnamese children with a known oral cleft. SETTING: The children were
      screened at local dental hospitals in five different cities in southern Vietnam.
      PARTICIPANTS: One hundred fifty-four children aged 4 to 6, 11 to 13, and 14 to 16
      years old with a cleft lip, cleft palate, or both were included in the study.
      OUTCOME MEASUREMENTS: For every age group, clefts were divided in four types. The
      dmft/DMFT was specified according to criteria of the World Health Organization
      (1997). RESULTS: The mean number of teeth affected by caries was 9.95 for 4- to 6
      year-old children, 2.97 for 11- to 13-year-old children, and 4.93 for 14- to 16
      year-old children, respectively. Four- to 6-year-old children with a unilateral
      or bilateral cleft lip and palate had significantly more caries and a higher dmft
      (decayed, missing, and filled teeth index) than children of the same age with
      only a cleft lip or a cleft lip and alveolus. CONCLUSIONS: Vietnamese children
      with an oral cleft have high numbers of teeth affected by dental caries, and
      special attention will be necessary for their oral health.

PMID- 15516167
TI  - The effect of infant orthopedics on the occlusion of the deciduous dentition in
      children with complete unilateral cleft lip and palate (Dutchcleft).
AB  - OBJECTIVE: Evaluation of the effect of infant orthopedics (IO) on the occlusion
      of the deciduous dentition in patients with unilateral cleft lip and palate
      (UCLP). DESIGN: Prospective, two-arm, randomized, controlled clinical trial with
      three participating cleft palate centers (Dutchcleft). SETTING: Cleft Palate
      Centers of the University Medical Center Nijmegen, Academic Center of Dentistry
      Amsterdam, and Dijkzigt University Hospital Rotterdam, The Netherlands. PATIENTS:
      Children with complete UCLP (n = 54) were included. INTERVENTIONS: In a concealed
      allocation procedure, half of the patients was randomized to wear a plate till
      surgical closure of the soft palate (IO+), and the other half (IO-) did not have
      a plate. MEAN OUTCOME MEASURES: Dental arch relationships were assessed at 4 and
      6 years of age with the 5-year-old index; the Huddart-score; and measurements of
      overjet, overbite, and sagittal occlusion. RESULTS: There were no significant
      differences found between the IO+ and IO- groups for the 5-year-old index; the
      Huddart-score; and overjet, overbite, and sagittal occlusion. CONCLUSIONS: IO had
      no observable effect on the occlusion in the deciduous dentition at 4 and 6 years
      of age. Considering the occlusion only, there is no need to perform IO in
      children with UCLP.

PMID- 15516168
TI  - Chronology and sequence of eruption of the permanent teeth in patients with
      complete unilateral cleft lip and palate.
AB  - OBJECTIVE: To establish the chronology and sequence of eruption of the permanent
      teeth in subjects with complete unilateral cleft lip and palate. DESIGN: Cross
      sectional. Data on children presenting complete cleft lip and palate were
      evaluated. SETTING: The study was carried out at the Hospital for Rehabilitation
      of Craniofacial Anomalies, Bauru, Sao Paulo, Brazil. SAMPLE: The sample comprised
      477 patients with complete unilateral cleft lip and palate, aged 5 to 14 years.
      Of these patients, 166 were girls and 311 were boys. RESULTS: The girls
      presented, for all maxillary and mandibular teeth, a smaller mean age of eruption
      than the boys. The maxillary lateral incisor and cuspid adjacent to the cleft
      presented significantly higher mean ages of eruption than their homologous teeth
      on the noncleft side.

PMID- 15516169
TI  - Photographs of study casts: an alternative medium for rating dental arch
      relationships in unilateral cleft lip and palate.
AB  - OBJECTIVE: To investigate the reliability of using photographs of study casts as
      an alternative to casts for rating dental arch relationships. DESIGN: Repeated
      measures study. SETTING: Cleft Palate Center of the University Medical Center
      Nijmegen, Nijmegen, The Netherlands. PATIENTS: Records of children with complete
      unilateral cleft lip and palate (UCLP) (n = 49) at the age of 9 years were
      included. MEAN OUTCOME MEASURE(S): Statistics of intra- and interexaminer
      agreement. RESULTS: No significant differences were found between the rating of
      dental casts and photographs of dental casts, using the Goslon Yardstick.
      CONCLUSIONS: Photographs of dental casts provide a consistent, reproducible
      method for rating dental arch relationships in patients with UCLP at the age of 9
      years and provide a reliable alternative to the application of the Goslon
      Yardstick on dental casts.

PMID- 15516170
TI  - Dental maturation in children with shunt-treated hydrocephalus.
AB  - OBJECTIVE: The aim of this study was to examine the relationship between dental
      maturation and somatic development and to discover their possible deviations in
      children with shunt-treated hydrocephalus. DESIGN: Radiographs (orthopantomogram
      and hand-wrist radiograph) from children with shunt-treated hydrocephalus were
      analyzed with respect to the dental maturation and compared with values of an age
      and sex-matched control group and population standards. PATIENTS: Forty-one
      children with shunt-treated hydrocephalus (27 boys and 14 girls) aged from 5 to
      16 years (median age 11.0 years). RESULTS: The mean deviation of dental age from
      chronological age was significantly greater in the hydrocephalic group than in
      the control group. The mean value of dental age deviation was advanced in early
      pubertal stages but reduced in later pubertal stages. CONCLUSIONS: These findings
      can be explained by changes in the endocrinological conditions, which are due to
      disturbed pituitary secretion. The present results could also partly reflect an
      adaptable developmental pathway in an otherwise strictly genetically determined
      process.

PMID- 15516171
TI  - The use of Spanish language educational materials by American cleft palate
      craniofacial association teams.
AB  - OBJECTIVE: The goals of this study were to assess U.S.-based American Cleft
      Palate-Craniofacial Association (ACPA) teams' use and perceived need for Spanish
      language educational materials and to evaluate trends in number of Spanish
      speaking patients treated. METHODS: A facsimile survey was sent to U.S.-based
      teams listed in the ACPA 1999 to 2000 and 2001 to 2002 Team Directories.
      Questions addressed demographics for Spanish-speaking patients/families and use
      of Spanish-language educational materials. Teams with a recent increase in
      Spanish speakers, 25% or more Spanish speakers, or both received a more in-depth
      follow-up survey. RESULTS: Response rate to the initial survey was 71%. Almost
      16% of teams reported having greater than 25% primarily Spanish speakers. Forty
      four percent of responders saw an increase in Spanish speakers over the past 5
      years, and 41% of responders used Spanish-language materials of some type. Fifty
      seven teams were sent a follow-up survey and 29 (51%) teams responded. Teams
      reported a need for more Spanish-language educational materials on specific
      craniofacial conditions, and many expressed frustration in communication and
      interaction with Spanish speakers. CONCLUSIONS: Many U.S.-based ACPA teams
      reported an increase in primarily Spanish speakers and expressed a need for more
      Spanish-language educational materials in different formats. Consideration of the
      diverse dialectic, cultural, and literacy needs of U.S. Spanish speakers can
      contribute to more effective educational efforts and improved care of the
      increasing number of Latinos treated by ACPA teams.

PMID- 15516172
TI  - Evaluation of oral and nasal odor in patients with and without cleft lip and
      palate: preliminary report.
AB  - OBJECTIVE: To evaluate oral and nasal halitosis parameters in patients with and
      without clefts. DESIGN: Randomized and prospective study. Patients with and
      without clefts were evaluated as to oral and nasal halitosis. SETTING: University
      of Sao Paulo, Bauru Dental School and Hospital for Rehabilitation of Craniofacial
      Anomalies, Bauru, Brazil. PATIENTS: Twelve patients with clefts and 12 without
      clefts were evaluated, and no exclusion criteria were followed. INTERVENTIONS:
      Nasal and oral halitosis were measured with the use of a portable sulfide monitor
      during a single visit. RESULTS: One hundred percent of the patients with clefts
      had altered values for volatile sulfur compounds. Only 33.3% of the patients
      without clefts had at least one strong value for nasal halimeter measurements,
      and 58.3% of these patients showed alteration in the nasal values. Statistical
      evaluation, made using the Mann-Whitney U test, classifying the nasal halimeter
      values as normal, weak, and strong, showing a statistical significant group
      difference (p = .003). There was no significant difference in the oral halimeter
      values between the two groups. CONCLUSIONS: Patients with cleft lip and palate
      had a tendency to present higher values for the nasal halimeter measurements,
      when compared with patients without clefts.

PMID- 15516173
TI  - Mandibular widening by distraction osteogenesis in the treatment of a constricted
      mandible and telescopic bite.
AB  - OBJECTIVE: Documentation of the application of mandibular widening by distraction
      osteogenesis and orthodontics. PATIENTS: Three patients with telescopic bite
      resulting from an extremely constricted mandible related to hypoglossia
      hypodactyly syndrome. INTERVENTION: Mandibular widening by distraction
      osteogenesis using an extraoral device and subsequent orthodontic treatment.
      RESULTS: The extremely constricted mandible and telescopic bite were dramatically
      improved by mandibular widening using distraction osteogenesis and subsequent
      orthodontics. Two of the three patients had transient complications; one reported
      temporomandibular joint pain and the other showed evidence of periodontal damage.
      CONCLUSION: Mandibular widening by distraction osteogenesis is an effective
      technique for the treatment of telescopic bite resulting from an extremely
      constricted mandible.

PMID- 15516174
TI  - Economic implications of caregiving at midlife: comparing parents with and
      without children who have developmental disabilities.
AB  - We compared the economic well-being and maternal employment of parents whose
      children did or did not have developmental disabilities. This prospective study
      is a secondary analysis of data from the Wisconsin Longitudinal Study, collected
      when respondents were aged 18, 36, and 53, on average. Although the two groups
      were similar at age 18, income and savings differed markedly by age 53, but
      statistically significant differences were not found on other measures. Mothers
      of children with disabilities were less likely to have job spells lasting more
      than 5 years and had lower earnings when they were 36 years old. Further, there
      was a trend for them to be less likely to have full-time jobs as their children
      grew older.

PMID- 15516175
TI  - "Make it just as normal as possible with humor".
AB  - Perspectives on humor of families who have a member with a disability were
      examined using a qualitative methodology. Findings offer complex and challenging
      lessons for those who work with and for families of children with disabilities. I
      compared the traditional view that families of children with disabilities go
      through a constant process of grieving and sadness with newly emerging views of
      accepting relationships and making life as typical as possible with the help of
      humor.

PMID- 15516176
TI  - The "postmodern" heresy in special education: a sociological analysis.
AB  - The special education profession has witnessed a recent struggle between
      researchers who defend a positivistic approach to knowledge and practice and
      "postmodern" special educators who challenge that approach. In this analysis I
      utilize a sociological theory of heresy to examine the conflict between
      postmodern heresy and positivist orthodoxy. I also investigate the cultural model
      of the special education profession, a discursive definition of ideology and
      heresy, characteristics of heresy in an organization, and the presence of deep
      contradiction within agreement between orthodoxy and heresy. I conclude with an
      examination of the limitations of heresy theory and the democratic challenge
      facing the multiparadigmatic field of special education.

PMID- 15516177
TI  - Access to health care for individuals with developmental disabilities from
      minority backgrounds.
AB  - In this project we examined access to health care by individuals with
      developmental disabilities in Kansas from low-income populations and from
      minority backgrounds. Four criteria for determining access were employed:
      availability, accessibility, affordability, and appropriateness of care. Factors
      that pose barriers and that facilitate access are described and recommendations
      are set out, with particular reference to the 2002 Report of the Surgeon General
      of the United States, related to health status of people with mental retardation.

PMID- 15516178
TI  - Recruiting people with disabilities as research participants: challenges and
      strategies to address them.

PMID- 15516179
TI  - Eliminating Medicaid dentistry for adults with mental retardation.

PMID- 15516180
TI  - Rigidity and flexibility in diagnosing mental retardation in capital cases.

PMID- 15516181
TI  - Understanding persons with intellectual disabilities in the criminal justice
      system: indicators of progress?

PMID- 15516183
TI  - U.S. residential support recipients with ID/DD now exceed 400,000 after 30%
      increase in past decade: increases evident in all states.

PMID- 15516186
TI  - Therapeutic hypothermia after cardiac arrest.
AB  - Hypothermia is now standard care for some types of cardiac arrest.

PMID- 15516187
TI  - The hidden tragedy of offender deaths. The justice system could go further in
      supporting the needs of those it detains after they are returned to the
      community.
AB  - The justice system could go further in supporting the needs of those it detains
      after they are returned to the community.

PMID- 15516188
TI  - Age-related macular degeneration and its possible prevention.
AB  - Despite well publicised claims of the therapeutic value of dietary supplements
      and other new treatments, the evidence for their effectiveness is modest.

PMID- 15516189
TI  - Predicting death in young offenders: a retrospective cohort study.
AB  - OBJECTIVE: To examine predictors of death in young offenders who have received a
      custodial sentence using data routinely collected by juvenile justice services.
      DESIGN: A retrospective cohort of 2849 (2625 male) 11-20-year-olds receiving
      their first custodial sentence between 1 January 1988 and 31 December 1999 was
      identified. MAIN OUTCOME MEASURES: Deaths, date and primary cause of death
      ascertained from study commencement to 1 March 2003 by data-matching with the
      National Death Index; measures comprising year of and age at admission, sex,
      offence profile, any drug offence, multiple admissions and ethnic and Indigenous
      status, obtained from departmental records. RESULTS: The overall mortality rate
      was 7.2 deaths per 1000 person-years of observation. Younger admission age
      (hazard ratio [HR], 1.4; 95% CI, 1.0-1.9), repeat admissions (HR, 1.8; 95% CI,
      1.1-2.9) and drug offences (HR, 1.5; 95% CI, 1.0-2.1) predicted early death. The
      role of ethnicity/Aboriginality could only be assessed in cohort entrants from
      1996 to 1999. The Asian subcohort showed higher risk of death from drug-related
      causes (HR, 2.5; 95% CI, 1.1-5.5), more drug offences (relative risk ratio [RRR],
      13; 95% CI, 8.5-20.0) and older admission age (oldest group v youngest: RRR, 9.3;
      95% CI, 1.3-68.0) than non-Indigenous Australians. Although higher mortality was
      not identified in Indigenous Australians, this group was more likely to be
      admitted younger (oldest v youngest: RRR, 0.31; 95% CI, 0.15-0.63) and experience
      repeat admissions (RRR, 1.6; 95% CI, 1.0-2.4). CONCLUSIONS: Young offenders have
      a much higher death rate than other young Victorians. Early detention, multiple
      detentions and drug-related offences are indicators of high mortality risk. For
      these offenders, targeted healthcare while in custody and further mental
      healthcare and social support after release appear essential if we are to reduce
      the mortality rate in this group.

PMID- 15516190
TI  - Trends in the use of hospital beds by older people in Australia: 1993-2002.
AB  - OBJECTIVE: To determine trends in use of Australian acute hospital inpatient
      services by older patients. DESIGN AND DATA SOURCES: Secondary analysis of
      hospital data from the Australian Institute of Health and Welfare in the period
      1993-94 to 2001-02, with population data for this period from the Australian
      Bureau of Statistics. OUTCOME MEASURES: Population-based rates of hospital
      separations and bed utilisation. RESULTS: The Australian aged population (65
      years and older) increased by 18% compared with total population growth of 10%,
      yet the proportion of hospital beds occupied by older patients remained stable at
      47%. The most substantial changes were observed in the population aged 75 years
      and older, with separations increasing by 89%, length of stay reducing by 35% and
      bed utilisation increasing by 23%. However, rates of bed utilisation (in relation
      to population) declined among older groups (10% decline in per capita use in
      population 75 years and older), but increased in the younger population (1%
      increase in per capita use in people younger than 65 years). CONCLUSION:
      Important trends in use of inpatient services were identified in this study.
      These trends are contrary to common perception. Ageing of the Australian
      population was not associated with an increase in the proportion of hospital beds
      used by older patients.

PMID- 15516191
TI  - Impact of hepatitis A vaccination of Indigenous children on notifications of
      hepatitis A in north Queensland.
AB  - OBJECTIVE: To describe the impact of a hepatitis A vaccination program for
      Indigenous children in north Queensland. DESIGN: Enhanced surveillance of all
      notified cases of hepatitis A in north Queensland from 1996 to 2003. SETTING:
      North Queensland; population, 596 500 people, including about 6900 Indigenous
      children aged under five years. INTERVENTIONS: Hepatitis A vaccine was provided
      to Indigenous children in north Queensland from February 1999; two doses were
      recommended (at 18 months and 2 years of age), as was catch-up vaccination up to
      the sixth birthday. RESULTS: In the 4 years 1996-1999, 787 cases of hepatitis A
      were notified in north Queensland, 237 (30%) of which were in Indigenous people.
      The average annual notification rates in Indigenous and non-Indigenous people
      during this period were 110 and 25 cases per 100 000 persons, respectively. In
      the first 4 years after introduction of the vaccination program (2000-2003), 66
      cases of hepatitis A were notified. Only nine of the 66 (14%) were in Indigenous
      people. The average annual notification rates in Indigenous and non-Indigenous
      people in 2000-2003 were 4 and 2.5 cases per 100 000 persons, respectively.
      CONCLUSION: Hepatitis A seems to have been eradicated from Indigenous communities
      in north Queensland very soon after the vaccination program began. The rapid
      decline in notifications in non-Indigenous as well as Indigenous people suggests
      the program quickly interrupted chains of transmission from Indigenous children
      to the broader community. To our knowledge this is the first evidence that a
      hepatitis A vaccination program targeting a high-risk population within a
      community can reduce disease in the broader community. Hepatitis A vaccine should
      be provided to other high-risk Indigenous children elsewhere in Australia.

PMID- 15516192
TI  - Postnatal evaluation of vitamin D and bone health in women who were vitamin D
      deficient in pregnancy, and in their infants.
AB  - OBJECTIVE: To determine the postnatal vitamin D status and bone health of women
      identified as vitamin D-deficient in pregnancy, and of their infants. DESIGN AND
      PARTICIPANTS: Retrospective audit conducted between 27 August and 5 November
      2003. The study included women delivering between August and October 2002 at the
      Royal Women's Hospital, Melbourne, who had had a 25-hydroxyvitamin D (25-[OH]D)
      level < 30 nmol/L in pregnancy, and their infants at age 4-10 months. SETTING:
      The outpatient clinic at the Royal Children's Hospital, Melbourne. MAIN OUTCOME
      MEASURES: Maternal and infant serum levels of vitamin D, total alkaline
      phosphatase (tALP), parathyroid hormone (PTH), calcium and phosphorus; x-ray
      results in children with clinical or laboratory findings suggestive of rickets.
      RESULTS: Of 69 mother-infant pairs invited to participate, 47 (68%) attended. All
      47 women had 25-(OH)D levels < 50 nmol/L, and 39 (83%) had levels < 30 nmol/L.
      Vitamin D supplements had been prescribed in pregnancy for 35 women (74%), and
      19/35 reported having taken them as prescribed. None had continued to take
      supplements postnatally, but one had recently started taking them again. Among 45
      infants from whom blood samples were successfully obtained, 18 (40%) had 25-(OH)D
      levels < 50 nmol/L, and 14 (31%) had levels < 30 nmol/L. Twelve of 16 breastfed
      infants had 25-(OH)D levels < 30 nmol/L, compared with 2/29 fed formula milk (P =
      0.001). CONCLUSIONS: Most mothers who had been vitamin D-deficient in pregnancy
      were also deficient postnatally, indicating that treatment offered, counselling
      and/or treatment compliance were inadequate. Their infants, especially if
      breastfed, were at high risk of vitamin D deficiency and increased bone
      formation. Breastfed infants of mothers at high risk of vitamin D deficiency
      should receive vitamin D supplements.

PMID- 15516193
TI  - The obesity epidemic: both energy intake and physical activity contribute.
AB  - Recent data from Australia, the United States and Europe show increased self
      reported energy intake associated with obesity, in contrast to earlier
      suggestions that the obesity epidemic has occurred despite minimal or no increase
      in per capita energy intake from food. The effect of increased energy intake is
      compounded by sedentary lifestyles. Both physical activity and nutrition must be
      addressed to reduce the prevalence of obesity and improve the health of
      Australians.

PMID- 15516194
TI  - Warfarin reversal: consensus guidelines, on behalf of the Australasian Society of
      Thrombosis and Haemostasis.
AB  - For most warfarin indications, the target maintenance international normalised
      ratio (INR) is 2-3. Risk factors for bleeding complications with warfarin use
      include age, history of past bleeding and specific comorbid conditions. To
      reverse the effects of warfarin, vitamin K(1) can be given. Immediate reversal is
      achieved with a prothrombin complex concentrate (PCC) and fresh frozen plasma
      (FFP). Vitamin K(1) is essential for sustaining the reversal achieved by PCC and
      FFP. When oral vitamin K(1) is used for warfarin reversal, the injectable
      formulation of vitamin K(1) is preferable to tablets because of its flexible
      dosing; this formulation can be given orally or injected. To temporarily reverse
      the effect of warfarin when there is a need to continue warfarin therapy, vitamin
      K(1) should be given in a dose that will quickly lower the INR to a safe, but not
      subtherapeutic, range and will not cause resistance once warfarin is reinstated.
      Prothrombinex-HT is the only PCC approved in Australia and New Zealand for
      warfarin reversal. It contains factors II, IX and X, and low levels of factor
      VII. FFP should be added to Prothrombinex-HT as a source of factor VII when used
      for warfarin reversal. Simple dental or dermatological procedures may not require
      interruption to warfarin therapy. If necessary, warfarin therapy can be withheld
      5 days before elective surgery, when the INR usually falls to below 1.5 and
      surgery can be conducted safely. Bridging anticoagulation therapy for patients at
      high risk for thromboembolism should be undertaken in consultation with the
      relevant experts.

PMID- 15516195
TI  - A limited form of Churg-Strauss syndrome presenting without asthma and
      eosinophilia.
AB  - We report a young woman presenting with digital gangrene, paranasal sinusitis,
      mononeuritis multiplex, and rapidly progressive glomerulonephritis without asthma
      and eosinophilia - an extremely rare variant of this disease.

PMID- 15516196
TI  - Near-drowning treated with therapeutic hypothermia.

PMID- 15516197
TI  - Teaching on the run tips 6: determining competence.

PMID- 15516198
TI  - Paediatrics: tackling the common problems.

PMID- 15516199
TI  - 1. Problem crying in infancy.
AB  - Up to 20% of parents report a problem with infant crying or irritability in the
      first 3 months of life. Crying usually peaks at 6 weeks and abates by 12-16
      weeks. For most irritable infants, there is no underlying medical cause. In a
      minority, the cause is cow's milk and other food allergy. Only if frequent
      vomiting (about five times a day) occurs is gastro-oesophageal reflux a likely
      cause. It is important to assess the mother-infant relationship and maternal
      fatigue, anxiety and depression. Management of excessive crying includes:
      explaining babies' normal crying and sleeping patterns; helping parents help
      their baby deal with discomfort and distress through a baby-centred approach;
      helping parents recognise when their baby is tired and apply a consistent
      approach to settling their baby; encouraging parents to accept help from friends
      and family, and to simplify household tasks. If they are unable to manage their
      baby's crying, admission to a parenting centre (day stay or overnight stay) or
      local hospital should be arranged.

PMID- 15516200
TI  - Obtaining consent affects the value of the Western Australian autism register.

PMID- 15516201
TI  - The expanding phenotype of cystic fibrosis.

PMID- 15516202
TI  - Are the Australian guidelines asking too much of the Pneumonia Severity Index
      (PSI)?

PMID- 15516203
TI  - The Australian government's review of positron emission tomography: evidence
      based policy decision-making in action.

PMID- 15516204
TI  - Medical education and hard science.

PMID- 15516205
TI  - Managing medical indemnity: must we choose between quality assurance and risk
      management?

PMID- 15516206
TI  - Missed peptic ulcer: a salutary lesson.

PMID- 15516207
TI  - Arachidonic acid inhibits the store-operated Ca2+ current in rat liver cells.
AB  - Vasopressin and other phospholipase-C-coupled hormones induce oscillations
      (waves) of [Ca2+]cyt (cytoplasmic Ca2+ concentration) in liver cells. Maintenance
      of these oscillations requires replenishment of Ca2+ in intracellular stores
      through Ca2+ inflow across the plasma membrane. While this may be achieved by
      SOCs (store-operated Ca2+ channels), some studies in other cell types indicate
      that it is dependent on AA (arachidonic acid)-activated Ca2+ channels. We studied
      the effects of AA on membrane conductance of rat liver cells using whole-cell
      patch clamping. We found no evidence that concentrations of AA in the
      physiological range could activate Ca2+-permeable channels in either H4IIE liver
      cells or rat hepatocytes. However, AA (1-10 microM) did inhibit (IC50=2.4+/-0.1
      microM) Ca2+ inflow through SOCs (ISOC) initiated by intracellular application of
      Ins(1,4,5)P3 in H4IIE cells. Pre-incubation with AA did not inhibit ISOC
      development, but decreased maximal amplitude of the current. Iso-tetrandrine,
      widely used to inhibit receptor-activation of phospholipase A2, and therefore AA
      release, inhibited ISOC directly in H4IIE cells. It is concluded that (i) in rat
      liver cells, AA does not activate an AA-regulated Ca2+-permeable channel, but
      does inhibit SOCs, and (ii) iso-tetrandrine and tetrandrine are effective
      blockers of CRAC (Ca2+-release-activated Ca2+) channel-like SOCs. These results
      indicate that AA-activated Ca2+-permeable channels do not contribute to hormone
      induced increases or oscillations in [Ca2+]cyt in liver cells. However, AA may be
      a physiological modulator of Ca2+ inflow in these cells.

PMID- 15516208
TI  - A mitochondrial pool of sphingomyelin is involved in TNFalpha-induced Bax
      translocation to mitochondria.
AB  - We recently showed that targeting bSMase (bacterial sphingomyelinase)
      specifically to mitochondria caused accumulation of ceramide in mitochondria, and
      induced cytochrome c release and cell death [Birbes, El Bawab, Hannun and Obeid
      (2001) FASEB J., 15, 2669-2679]. In the present study, we investigated the role
      of this mitochondrial pool of ceramide in response to a receptor-mediated event,
      namely TNFalpha (tumour necrosis factor alpha), and the involvement of this
      mitochondrial pool of ceramide in Bax translocation to mitochondria, an event
      that precedes cytochrome c release. Treatment of MCF7 cells with TNFalpha caused
      an increase in ceramide levels in the mitochondrial fraction which accompanied
      Bax translocation to mitochondria. Targeting bSMase to mitochondria specifically
      resulted in Bax translocation to mitochondria, suggesting that the mitochondrial
      ceramide pool is involved in Bax translocation. Moreover, in a reconstituted cell
      free system, treatment of isolated mitochondria with bSMase enhanced Bax
      association with mitochondrial membranes. Collectively, these results suggest
      that the generation of ceramide in mitochondria in response to TNFalpha is
      sufficient to induce Bax translocation to mitochondria and subsequent cytochrome
      c release and cell death.

PMID- 15516211
TI  - Consent, commodification and benefit-sharing in genetic research.
AB  - The global value of the biotechnology industry is now estimated at 17 billion
      dollars, with over 1300 firms involved as of the year 2000.(2) It has been said
      that 'What we are witnessing is nothing less than a new kind of gold rush, and
      the territory is the body.' As in previous gold rushes, prospectors are flooding
      into unexplored and 'wide open' territories from all over the world, with
      possible ramifications for exploitation of Third World populations. These
      territories are also the Wild West of bioethics insofar as the law has very
      little hold on them: existing medical and patent law, such as the Moore and
      Chakrabarty cases, exert little control over powerful economic interests in both
      the United States and Europe. In the absence of a unified and consistent law on
      property in the body, the focus is increasingly on refining the consent approach
      to rights in human tissue and the human genome, with sensitive and promising
      developments from the Human Genetics Commission and the Department for
      International Development consultation on intellectual property. These
      developments incorporate the views of vulnerable genetic communities such as
      Native Americans or some Third World populations, and should be welcomed because
      they recognise the power imbalance between such groups and First World
      researchers or firms. However, they also highlight the continued tension about
      what is really wrong with commodifying human tissue or the human genome. Where's
      the injustice, and can it be solved by a more sophisticated consent procedure?

PMID- 15516209
TI  - Transcriptional modulation of the pre-implantation embryo-specific Rnf35 gene by
      the Y-box protein NF-Y/CBF.
AB  - Maternal-to-zygotic transition of a fertilized egg and the subsequent pre
      implantation development of the embryo involve zygotic genome activation and
      reprogramming of gene expression. The goal of the present study is to establish a
      model suitable for the characterization of transcriptional modulation of
      mammalian pre-implantation development. Rnf35 is a mouse RING-finger protein gene
      that is temporally transcribed in the early embryo, but is permanently silenced
      before the blastocyst stage of development. We first show that the Chinese
      hamster ovary-K1 cells are unique in supporting Rnf35 promoter activities in
      transient transfection assays. Using the permissive Chinese-hamster ovary-K1 cell
      line, we show that Rnf35 transcription is driven by an Inr (initiator) core
      promoter element in the absence of a TATA box; the Inr promoter function is
      confirmed by direct microinjection of mouse one-cell embryos. This is the first
      demonstration of the involvement of an Inr core promoter element in transcription
      in pre-implantation development. We show that the Rnf35 promoter is regulated by
      three obligatory Y-box (CCAAT-box) elements: two Y boxes (Y(I) and Y(II)) located
      at -81 are coupled in a palindrome and act synergistically in contributing to
      Rnf35 transcription; the third Y box (Y(III)) is situated at -13, just upstream
      of the Inr element, and may be an integral part of the Inr function.
      Electrophoretic mobility-shift assays and competition experiments further reveal
      that the Y(I) box is bound by the ubiquitous NF-Y (nuclear factor-Y)/CBF (CCAAT
      binding factor) and that Y(II) is targeted by an unidentified protein(s) that
      acts synergistically with the NF-Y. We suggest that the NF-Y, targeting at a Y
      box sequence, may function as an important activator in transcriptional
      regulation of the Rnf35 gene in the pre-implantation embryo.

PMID- 15516212
TI  - Bioethics, biotechnology and culture: a voice from the margins.
AB  - In this paper I argue for the universality of morality as against and in spite of
      the plurality and inevitable relativity of human cultures. Universalisability is
      the litmus test of moral authenticity whereas culture tends to impose an
      egocentric predicament. I argue equally for the equality of cultures qua cultures
      and of the importance of different cultural perspectives, given the limitations
      of each and every particular culture, in a balanced and wholesome appreciation of
      moral issues, particularly issues of cross-cultural relevance. I then try to
      anchor my reflections on a few topical ethical issues of cross-cultural relevance
      which have been the subject of controversy in recent times.

PMID- 15516213
TI  - Ethics and health systems research in 'post'-conflict situations.
AB  - Although considerable attention has been given to ethical issues related to
      clinical research in developing countries, in particular related to HIV therapy,
      there has been limited focus on health systems research, despite its increasing
      importance in the light of current trends in development assistance. This paper
      examines ethical issues related to health systems research in 'post'-conflict
      situations, addressing both generic issues for developing countries and those
      issues specific to 'post'-conflict societies, citing examples from the author's
      Cambodian experience. It argues that the destruction of health infrastructure
      results in a loss of structures and processes that would otherwise protect
      prospective research subjects who are part of vulnerable populations. It
      identifies the growth of health systems research as part of a trend towards
      sectoral and programmatic development assistance, the emergence of 'knowledge
      generation' as a form of research linked to development, and the potential for
      conflict where multilateral and bilateral donors are both primary funders and
      users of health systems research. It also examines the position of the health
      system researcher in relation to the sponsors of this research, and the health
      system being analysed.

PMID- 15516214
TI  - The current situation of health research and ethics in Sudan.
AB  - At the beginning of the twentieth century, health research in the Sudan developed
      primarily as a function of the colonial British administration. Ethical issues in
      the medical profession in the Sudan are governed by the Sudan Medical Council. To
      address these issues, the Sudan Medical Council issued Medico-legal and Ethical
      Guidelines in 1967. This important document has focused principally on ethical
      issues arising in clinical medicine. Throughout the history of health research in
      Sudan it is very difficult to find any reference to research ethics.
      Nevertheless, there have been a few attempts to articulate ethics in health
      research. In 1979, Sudan witnessed the establishment of the first ethical review
      committee, which was established by the initiative of a group of doctors and
      scientists from the national health research laboratory. This committee got
      neither political nor institutional recognition. Therefore, it was not developed
      and came to an end shortly after its inception. Yet, in 2000 the FMOH established
      an ethical review committee (ERC). The functions of this committee were to review
      proposals of health research to be carried out in the country for ethical issues
      irrespective to the funding agents. Unfortunately, the committee devoted all the
      jobs in reviewing only externally-sponsored health research and research carried
      out by expatriate researchers or international organisations.

PMID- 15516215
TI  - Current trends in teaching ethics of healthcare practices.
AB  - The unprecedented progress in bio-medical sciences and technology during the last
      few decades has resulted in great transformations in the concepts of health and
      disease, health systems and healthcare organisation and practices. Those changes
      have been accompanied by the emergence of a broad range of ethical dilemmas that
      confront health professionals more frequently. The classical Hippocratic ethical
      principles, though still retaining their relevance and validity, have become
      insufficiently adequate in an increasing range of problems and situations.
      Healthcare that has been practised for centuries on the basis of a direct doctor
      patient relationship has been increasingly transformed into a more complex
      process integrating the health-team, the patient (healthcare seeker) and the
      community. Systematic review of the specialised literatures revealed that
      Healthcare Ethics education has become a basic requirement for any training
      programme for health professionals, and should cover the different stages of
      undergraduate, postgraduate and continuing education. Both theoretical
      foundations and practical skills are required for the appropriate ethical
      reasoning, ethical attitude and decision-making abilities. There is growing
      evidence that physicians' professional and moral development is not only
      determined by the formal curriculum of ethics; rather more, it is determined by
      the moral environment of the professional practice, the 'hidden curriculum' which
      deserves serious consideration by medical education.

PMID- 15516216
TI  - Research sponsors duties to developing world host nations: the ongoing WMA
      discussion of possible revisions to the 2000 Declaration of Helsinki (paragraph
      30).

PMID- 15516221
TI  - An ultrastructural study of cellular response to variation in porosity in phase
      pure hydroxyapatite.
AB  - Hydroxyapatite has been shown to be biocompatible and bioactive. Incorporation of
      porosity has been shown to enhance osteointegration; however, difficulty in
      controlling the extent and type of porosity has limited investigation into
      determining the role of both macro- and microporosity. The current investigation
      reports on the synthesis of four types of phase-pure hydroxyapatite with varying
      levels of porosity (HA1-HA4), and with defined levels of macro- and
      microporosities. Transmission electron microscopy was used to evaluate
      qualitatively the effect of these two parameters on cell-material interactions
      following a 30-day incubation period. Biological mineralization was observed
      within vesicles and the needle-like minerals were confirmed as hydroxyapatite
      using X-ray microanalysis. This demonstrated the suitability of primary human
      osteoblast-like cells as a tool to assess the extent of mineralization.
      Furthermore, internalization of hydroxyapatite particles was observed. Our
      findings show that the variation in macro- and microporosity does not affect the
      extent of cell-material interaction, with collagen synthesis evident in all
      samples.

PMID- 15516222
TI  - Index for spatial heterogeneity in breast cancer.
AB  - Histopathological heterogeneity in cancer is a general concern. Breast carcinoma
      heterogeneity is now widely admitted as a source of histological grading
      imprecision and reproducibility problems. Classically, homogeneity is defined as
      equivalent to stationarity. A measure of heterogeneity based on asymptotic
      properties of spatial statistics is developed. Long-range dependences in
      heterogeneous spatial processes make estimation of the proposed heterogeneity
      measure unreliable. A robust estimator based on the wavelet transform is
      presented; this bypasses long-range dependences. The estimator extends previous
      works on one-dimensional stochastic processes to two dimensions as appropriate
      for histopathological analysis. As a side result, the estimator gives confidence
      intervals for the heterogeneity measure that enables the formulation and
      validation of testable hypothesis on the observed histopathological samples. This
      approach is applied to the characterization of breast cancer tumours. We show
      that the heterogeneity measure for various blocks of a single tumour is
      invariable, even when various blocks differ in size and in number of marked
      nuclei.

PMID- 15516223
TI  - Crystal orientation mapping of NiO grown on cube textured Ni tapes.
AB  - Samples of cube textured Ni tapes were oxidized in flowing oxygen at different
      temperatures. Crystal orientation maps (COMs) of the resulting oxide layers were
      produced by electron backscatter diffraction. The oxide layers were also analysed
      by X-ray diffraction (XRD), scanning electron microscopy and atomic force
      microscopy (AFM). The oxide grain size of a sample oxidized at 600 degrees C was
      similar to that of the substrate and the oxide was highly textured, both
      indicating epitaxial growth. The orientation relationship between the substrate
      and the oxide was directly observed from XRD to be (111)NiO//(001)Ni,
      [101]NiO//[110]Ni with four, equivalent, in-plane variants. In each variant, the
      oxide has both <110>- and <211>-type directions parallel to the Ni <110>
      directions. Differences in oxide thickness and surface roughness on neighbouring
      grains were revealed by AFM and these were attributed to the existence of a range
      of oxide growth conditions resulting from small differences in the orientation of
      each substrate grain. Similar macrotexture and microstructure were observed on a
      sample oxidized at 1300 degrees C, but additional, facetted oxide crystals had
      formed at the oxide grain boundaries. COMs showed that these crystals were either
      cube or 45 degrees rotated cube orientated, a texture different to that of the
      large oxide grains. The grain boundary crystals were thought to form by inward
      diffusion of oxygen at defects in the growing oxide scale.

PMID- 15516224
TI  - Automatic real-time three-dimensional cell tracking by fluorescence microscopy.
AB  - Live cell imaging has become an indispensable technique for cell biologists.
      However, when grown on coverslip glass used for live cell imaging many cultured
      cells move even during relatively short observation times and focus can drift as
      a result of mechanical instabilities and/or temperature fluctuations. Time-lapse
      imaging therefore requires constant adjustment of the imaging field and focus
      position to keep the cell of interest centred in the imaged volume. We show here
      that this limitation can be overcome by tracking cells in a fully automated way
      using the mass centre of cellular fluorescence. Combined with automated multiple
      location revisiting, this method dramatically increases the throughput of high
      resolution live cell imaging experiments.

PMID- 15516225
TI  - Signal analysis of total internal reflection fluorescent speckle microscopy (TIR
      FSM) and wide-field epi-fluorescence FSM of the actin cytoskeleton and focal
      adhesions in living cells.
AB  - Fluorescent speckle microscopy (FSM) uses low levels of fluorescent proteins to
      create fluorescent speckles on cytoskeletal polymers in high-resolution
      fluorescence images of living cells. The dynamics of speckles over time encode
      subunit turnover and motion of the cytoskeletal polymers. We sought to improve on
      current FSM technology by first expanding it to study the dynamics of a non
      polymeric macromolecular assembly, using focal adhesions as a test case, and
      second, to exploit for FSM the high contrast afforded by total internal
      reflection fluorescence microscopy (TIR-FM). Here, we first demonstrate that low
      levels of expression of a green fluorescent protein (GFP) conjugate of the focal
      adhesion protein, vinculin, results in clusters of fluorescent vinculin speckles
      on the ventral cell surface, which by immunofluorescence labelling of total
      vinculin correspond to sparse labelling of dense focal adhesion structures. This
      demonstrates that the FSM principle can be applied to study focal adhesions. We
      then use both GFP-vinculin expression and microinjected fluorescently labelled
      purified actin to compare quantitatively the speckle signal in FSM images of
      focal adhesions and the actin cytoskeleton in living cells by TIR-FM and wide
      field epifluorescence microscopy. We use quantitative FSM image analysis software
      to define two new parameters for analysing FSM signal features that we can
      extract automatically: speckle modulation and speckle detectability. Our analysis
      shows that TIR-FSM affords major improvements in these parameters compared with
      wide-field epifluorescence FSM. Finally, we find that use of a crippled
      eukaryotic expression promoter for driving low-level GFP-fusion protein
      expression is a useful tool for FSM imaging. When used in time-lapse mode, TIR
      FSM of actin and GFP-conjugated focal adhesion proteins will allow quantification
      of molecular dynamics within interesting macromolecular assemblies at the ventral
      surface of living cells.

PMID- 15516226
TI  - Imaging cells on polymer spherulites.
AB  - Polymers are commonly used to construct tissue-engineered medical products and
      the conditions used to process these polymeric materials can affect their
      biological performance. For semi-crystalline polymers, thermal processing
      conditions can induce crystallization of the polymer chains into spherulites,
      which cause the polymer surface to become roughened. This change in surface
      topology can influence cell behaviours such as adhesion, morphology and
      proliferation. Herein, a simple microscope technique is presented, which combines
      fluorescence microscopy with transmitted white light microscopy using crossed
      polarizers. This technique allows simultaneous imaging of cells and polymer
      spherulites, which enables the biomaterials researcher to observe the effects of
      spherulites on cell alignment and morphology.

PMID- 15516227
TI  - Second-order stereology of spatial fibre systems.
AB  - This paper describes methods for second-order stereology of spatial fibre
      systems. For stationary and isotropic fibre processes it gives practicable
      estimators of the K-function and the pair correlation function, which are based
      on planar sections. The second-order methods are applied in transmission electron
      microscopy analysis of blood capillaries in the rat thyroid. They lead to the
      result that the capillaries show an inhibitory pattern of their spatial
      arrangement, with a hard-core distance of about 2.6 microm. There is a close
      relationship to three-dimensional size characteristics estimated recently for
      these elliptical capillaries.

PMID- 15516228
TI  - Structured illumination microscopy: artefact analysis and reduction utilizing a
      parameter optimization approach.
AB  - Practical applications of structured illumination microscopy (SIM) often suffer
      from various artefacts that result from imprecise instrumental hardware and
      certain bleaching properties of the sample. These artefacts can be observed as
      residual stripe patterns originating from the illumination grating. We
      investigated some significant causes of these artefacts and developed a
      correction approach that can be applied to images after acquisition. Most of the
      artefacts can be attributed to changes in illumination and detection intensities
      during acquisition. The proposed correction algorithm has been shown to be
      functional on noisy image data, and produces exceptional, artefact-free results
      in everyday laboratory work.

PMID- 15516229
TI  - Directional analysis of digitized three-dimensional images by configuration
      counts.
AB  - A method for estimating the orientated rose of normal directions of a three
      dimensional (3D) set Z from a digitization of Z, i.e. a voxel image, is
      presented. It is based on counts of informative configurations in n x n x n voxel
      cubes. An algorithm for finding all informative configurations is proposed and an
      estimation procedure is described in detail for the case n= 2. The presented
      method is a 3D version of a method of estimating the orientated rose of binary
      planar images using n x n configurations. A new feature is the design-based
      approach, being more appropriate for biomedical image analysis than the formerly
      applied model-based approach.

PMID- 15516230
TI  - Maximum pixel spectrum: a new tool for detecting and recovering rare,
      unanticipated features from spectrum image data cubes.
AB  - A new software tool, the maximum pixel spectrum, detects rare events within a
      spectrum image data cube, such as that generated with electron-excited energy
      dispersive X-ray spectrometry in a scanning electron microscope. The maximum
      pixel spectrum is a member of a class of 'derived spectra' that are constructed
      from the spectrum image data cube. Similar to a conventional spectrum, a derived
      spectrum is a linear array of intensity vs. channel index that corresponds to
      photon energy. A derived spectrum has the principal characteristics of a real
      spectrum so that X-ray peaks can be recognized. A common example of a derived
      spectrum is the summation spectrum, which is a linear array in which the
      summation of all pixels within each energy plane gives the intensity value for
      that channel. The summation spectrum is sensitive to the dominant features of the
      data cube. The maximum pixel spectrum is constructed by selecting the maximum
      pixel value within each X-ray energy plane, ignoring the remaining pixels. Peaks
      corresponding to highly localized trace constituents or foreign contaminants,
      even those that are confined to one pixel of the image, can be seen at a glance
      when the maximum pixel spectrum is compared with the summation spectrum.

PMID- 15516231
TI  - A convenient and rapid sample repositioning approach for atomic force microscopy.
AB  - A novel repositioning approach is described for repeated observations of a
      specimen at a close proximal location in the atomic force microscope. The
      approach is similar to keystone architecture, whereby the repositioning is
      achieved by forming a male structured base for the specimen, and a corresponding
      female counterpart as the frame. For the combination of an acrylic acid frame and
      a metal base, 90% translation shifts are less than 10 microm, and almost all
      angular disorientations are within +3 degrees to -3 degrees . Nanometre-scale
      surface features can be relocated easily and reliably even after 40 imaging
      removal-imaging cycles, dipping the specimen in solutions or heating up to 500
      degrees C.

PMID- 15516234
TI  - A report on the activity and clinical outcomes of renal non-heart beating donor
      transplantation in the United Kingdom.
AB  - The use of kidneys from non-heart beating donors (NHBDs) presents a paradox;
      whilst they provide more organs for transplantation, there is an increased risk
      of poor graft outcome, particularly in the short term. This study has highlighted
      the difference in early graft function and late graft survival between NHBD
      kidneys with short (controlled) and long (uncontrolled) warm ischaemic times.
      Whilst it would seem that it is preferable to use controlled donors only, their
      numbers are small. By employing a rational approach to the use of each of these
      types of kidney, such as structured viability assessment and risk analysis, it
      may be that the results of uncontrolled NHBD can be improved.

PMID- 15516235
TI  - Impact of body mass index on graft failure and overall survival following liver
      transplant.
AB  - GOALS: To assess the influence of body mass index (BMI) in the outcome of liver
      transplantation. BACKGROUND: Body mass index appears to affect liver
      transplantation, independently of several risk factors. STUDY: A review of the
      United Network for Organ Sharing database included 32 515 liver transplants from
      1992 through 2000 with at least one follow-up visit, of which 26 920 had
      information for determining BMI. The overall impact of elevated BMI (>25), and
      the impact of increasingly elevated BMI (25-40+) on graft failure rates and
      overall survival rates are assessed using proportional hazards regression.
      RESULTS: Controlling for follow-up time, age, gender, race, number of
      comorbidities, and status 1 designation, the impact of BMI on survival was mixed.
      The risk of death was elevated for patients with low BMI (<19) and BMI values of
      >/=40. Compared with patients with BMI of 19-22, those with BMI > 25 had a
      decreased likelihood of death. This decrease was seen among patients with BMI of
      25-34. CONCLUSION: BMI did not significantly affect rates of graft failure.
      Compared with patients with a BMI in the 'normal' range, those with moderately
      elevated BMI had decreased likelihood of death while patients with low BMI or
      extremely high BMI had increased likelihood of death.

PMID- 15516236
TI  - Influence of retrograde flushing via the caval vein on the post-reperfusion
      syndrome in liver transplantation.
AB  - INTRODUCTION: The reperfusion phase during orthotopic liver transplantation (LTX)
      is a critical event with sometimes profound hemodynamic and cardiac changes. We
      present the influence of retrograde reperfusion in LTX on the post-reperfusion
      syndrome (PRS). METHODS: Fifty-six LTXs in 53 patients were performed with the
      piggy-back technique with retrograde reperfusion via the caval vein and antegrade
      reperfusion via the portal vein. The incidence of PRS was evaluated. RESULTS: We
      observed a PRS in two patients (3.6%), four patients (7.1%) had a decrease in
      mean arterial pressure (MAP) of 20-29%, 18 patients (32.2%) of 10-19%, 27
      patients (48.2%) of 1-9% and five patients (8.9%) had a small increase in MAP.
      DISCUSSION: Our retrospective study showed that retrograde reperfusion seems to
      maintain stability during the reperfusion phase. Hemodynamic disturbances during
      LTX were uncommon, leading us to suppose that the incidence of PRS could be
      diminished with retrograde reperfusion.

PMID- 15516237
TI  - Dyslipidemia during sirolimus therapy in patients after liver transplantation.
AB  - INTRODUCTION: Sirolimus (SRL) is an immunosuppressive agent of potential benefit
      in clinical liver transplantation (LTX). One of the major side effects of SRL is
      hyperlipidemia, which is reported in up to 44% of patients. In this report, we
      describe the lipid profiles of 20 stable liver transplant recipients who received
      SRL for immunosuppression. METHODS: The study group received SRL in combination
      with tacrolimus and/or mycophenolate mofetil (MMF). The control group was
      administered calcineurin inhibitor (CI) and MMF. Fasting serum cholesterol level,
      high-density lipoproteins (HDL) and low-density lipoproteins (LDL) were measured
      regularly. Furthermore, the total cholesterol/HDL ratio and the LDL/HDL ratio
      were evaluated. Diabetes and hypertension were monitored as well. RESULTS: In the
      SRL group, hypercholesterolemia was found in three patients (15%) and
      hypertriglyceridemia in two patients (10%). There was no marked difference from
      the control group, although a higher association of SRL with hyperlipidemia was
      described in the literature. Furthermore, HDL and LDL levels were similar in both
      groups, as well as total cholesterol/HDL ratio and LDL/HDL ratio. Diabetes and
      hypertension had a similar incidence in both the groups. Thus, there was no
      difference concerning the cardiovascular atherosclerosis risk between the
      immunosuppressive protocol with SRL or with CI. DISCUSSION: The results of our
      retrospective study demonstrated that the immunosuppressive regimen can
      potentially influence the incidence of hyperlipidemia in patients after LTX. SRL
      in combination with tacrolimus and/or MMF had no higher incidence of
      hyperlipidemia than CI and MMF. The combination of immunosuppressive therapy with
      low dose and low levels of each immunosuppressive agent could decrease the risk
      of atherosclerosis and its complications in long-term survivors after LTX.

PMID- 15516238
TI  - Management of biliary tract complications after orthotopic liver transplantation.
AB  - INTRODUCTION: Despite improved survival, biliary complications remain a
      significant cause of morbidity following orthotopic liver transplantation. The
      aim of this study was to review the incidence, treatment and optimum management
      pathway of biliary complications at the Scottish Liver Transplant Unit. MATERIALS
      AND METHODS: All patient data were collected prospectively onto a database at the
      Scottish Liver Transplant Unit with review of hospital records for validation.
      RESULTS: A total of 379 consecutive orthotopic liver transplants were performed
      in 333 adult patients between November 1992 and September 2001. Biliary
      complications occurred in 55 grafts (51 patients) (14.6%) and their incidence
      decreased with time. Biliary complications occurred in 29 (10.9%) of the 265
      choledocho-choledochostomies compared with 14 (25%) of the 56 with T-tubes.
      Twenty-eight biliary leaks occurred, 22 of which were anastomotic. Seventeen
      anastomotic leaks were successfully treated non-operatively. Eight patients with
      biliary leaks subsequently developed an anastomotic stricture. Of the 30
      anastomotic strictures, stent insertion was successful in resolving six of 14
      (42%) early anastomotic strictures compared with one of 12 (8%) late anastomotic
      strictures (p = 0.0479). Six (38%) of the 16 early anastomotic strictures
      required surgery for complete resolution, compared with 12 (86%) of the 14 late
      anastomotic strictures (p = 0.0106). CONCLUSION: The incidence of biliary
      complications has decreased with time. The abandonment of choledocho
      choledochostomy over a T-tube has been justified. A combination of conservative,
      endoscopic, and radiological management has been effective in treating biliary
      leaks and early anastomotic stricture. However endoscopic or radiological
      stenting was ineffective in the management of late anastomotic strictures, which
      were best treated by surgical intervention.

PMID- 15516239
TI  - Cyclosporine pharmacokinetics in anti-HCV+ patients.
AB  - BACKGROUND: Cyclosporine (CsA) is a widely used immunosuppressive agent in kidney
      transplant patients. In Brazil, around 30% of patients awaiting kidney
      transplantation carry anti-HCV antibodies. Previous observations suggest altered
      CsA pharmacokinetics in these patients. METHODS: We conducted two pharmacokinetic
      studies. In the pre-transplant (pre-Tx) study, we examined 22 dialysis patients
      on chronic hemodialysis awaiting transplantation, 11 anti-HCV+ [seven polymerase
      chain reaction (PCR)-positive] matched against 11 controls. In the post
      transplant (post-Tx) study, we enrolled 24 kidney allograft recipients - 10 anti
      HCV+ (six PCR-positive), and 14 controls. In the first study, all patients
      received an 8-mg/kg dose of CsA microemulsion (ME). Secondly, the dosage was
      indicated by the patient's medical team. Pharmacokinetic parameters were
      calculated from 13 blood samples (0-12 h postdose) by fluorescence polarization
      immunoassay with specific monoclonal antibodies. RESULTS: In both studies,
      maximum concentration (C(max)), minimum concentration (C(min)) and area under the
      CsA time-concentration curve from 0 to 12 h (AUC(0-12)) were higher for anti-HCV+
      patients than for controls, but significantly so only for AUC(0-12) in the pre-Tx
      study (42%; p < 0.05). When PCR-positive patients were compared with controls,
      differences were amplified. In the pre-Tx study, differences were 58%, 69%, and
      91% higher in PCR-positive patients for C(max) (p = 0.05), AUC(0-12) (p < 0.01),
      and C(min) (p < 0.01), respectively. In the post-Tx study, results were 50% (p <
      0.01) and 32% (p < 0.01) higher in PCR-positive patients for C(max) and AUC(0
      12), respectively. In the pre-Tx study, the impact of viremia was significantly
      higher in female patients. CsA trough levels remained higher along the first year
      post-transplantation in viremic patients. CONCLUSIONS: Anti-HCV+ patients,
      especially those with viremia, present altered CsA pharmacokinetics, with higher
      peak levels and drug exposure than controls.

PMID- 15516240
TI  - Initial experience using histidine-tryptophan-ketoglutarate solution in clinical
      pancreas transplantation.
AB  - BACKGROUND: The colloid-based University of Wisconsin (UW) preservation solution
      has been used extensively in clinical pancreas transplantation. Experimental
      studies support the use of the crystalloid-based histidine-tryptophan
      ketoglutarate (HTK) preservation solution for this purpose. AIM: We report our
      initial experience with HTK for pancreas allograft preservation and compare this
      to a contemporary experience with UW solution in conventional multiorgan deceased
      donors (<50 yr). MATERIALS AND METHODS: Retrospectively collected information on
      33 pancreas transplants between September 2001 and October 2002 were analyzed for
      early graft function and complications up to 30 d after procurement and storage
      in either HTK or UW solutions. During multi-organ recovery, either UW solution (4
      5 L) or HTK solution (8-10 L) was used for aortic perfusion and subsequent back
      table flush and storage. Exocrine drainage of 31 pancreas allografts was enteric,
      while the bladder was used for drainage in two cases. Patient outcomes were
      analyzed according to the preservation solution used. Sixteen pancreata were used
      in combination with a kidney allograft (SPK), seven were used in patients after
      prior kidney transplantation (PAK), while 10 were used in patients who were not
      in renal failure (PTA). RESULTS: The UW group consisted of 17 patients (10 SPK,
      three PAK, four PTA) with a mean donor age of 29.5 +/- 10.7, and a mean cold
      ischemia time of 15.1 +/- 2.1 h. The mean post-transplant pancreas and kidney
      function on days 1 and 10 were amylase (315 and 99 IU/L), lipase (1727 and 346
      IU/L), glucose (121 and 100 mg/dL) and creatinine (5.01 and 1.77 mg/dL). Patient
      and graft survival was 100% at 1-month post transplant. In the HTK group there
      were 16 patients (six SPK, four PAK, six PTA) with a mean donor age 21.9 +/- 5.7
      and a mean cold ischemia time 14.0 +/- 1.3 h. The mean post-transplant pancreas
      and kidney function on days 1 and 10 were amylase (588 and 126 IU/L), lipase
      (4711 and 441 IU/L), glucose (97 and 109 mg/dL) and creatinine (5.28 and 2.42
      mg/dL). Patient survival was 100% while graft survival was 94% at 1-month post
      transplant. CONCLUSIONS: Early graft function and complications are comparable
      with HTK and UW solutions for pancreas allograft preservation.

PMID- 15516241
TI  - Tuberculous infection in southern Chinese renal transplant recipients.
AB  - A retrospective study of the prevalence and pattern of tuberculosis among renal
      transplant patients in a single centre in southern China was performed. Twenty
      three cases of tuberculosis were diagnosed among 440 patients between January
      1991 and December 2002. There were 18 men and five women. The mean age of the
      patients was 39.3 +/- 13.4 yr. There were 13 living-related and 10 cadaveric
      renal transplants. The interval between renal transplantation and the development
      of tuberculosis ranged from 3 to 127 months with a median of 46 months. There
      were 18 cases of pulmonary tuberculosis, two cases of pulmonary plus laryngeal
      tuberculosis, two cases of disseminated tuberculosis, and one case of
      tuberculosis involving the urinary tract. Diagnosis was established by positive
      culture for Mycobacterium tuberculosis in 21 patients and response to empirical
      anti-tuberculosis treatment in two patients. The duration of symptoms before the
      diagnosis of tuberculosis was 27 +/- 12 d. The patients were treated with
      standard anti-tuberculosis drugs for 11 +/- 3 months. The anti-tuberculosis
      treatment was in general well-tolerated. Five patients developed transient
      hepatitis, three patients developed thrombocytopenia and five patients developed
      gouty arthritis. One patient died 2 months after initiation of anti-tuberculosis
      therapy. All other patients completed anti-tuberculosis treatment. No recurrence
      of tuberculosis was observed after a median follow-up of 90 months. We concluded
      that (i) tuberculosis is prevalent among southern Chinese renal transplant
      recipients; (ii) high index of suspicion for tuberculosis among renal transplant
      recipients is warranted to ensure early diagnosis and prompt initiation of
      treatment; and (iii) treatment with standard anti-tuberculosis drugs for an
      extended period of time is well-tolerated and is associated with favourable
      outcome.

PMID- 15516242
TI  - Improving exercise capacity, 6 wk training tends to reduce circulating endothelin
      after heart transplantation.
AB  - Short-term survival is no longer the pivotal issue after heart transplantation
      but, most heart-transplant (Htx) patients still present with increased
      circulating endothelin-1 (ET) and reduced exercise capacity. ET-1 limits both
      exercise-induced vasodilation and blood flow redistribution toward acting muscles
      and might be accessible to training. This study was performed to investigate the
      effect of training on ET-1 and whether an eventual training-induced improvement
      in exercise capacity may be related to reduced baseline or exercise circulating
      ET-1 in Htx patients. Five Htx patients performed a maximal bicycle exercise test
      and an endurance exercise test before and after a training program of 18
      exercises sessions during 6 wk. ET-1 was determined by radioimmunoassay at rest,
      end endurance exercise and 30 min recovery, before and after training. Training
      improved significantly Htx's maximal oxygen uptake (+13.1 +/- 4.8%; p < 0.05) and
      also reduced significantly the endurance exercise-induced heart rate increase.
      Resting ET-1 was increased in Htx (5.98 +/- 1.88 vs. 1.61 +/- 0.25 pmol/L in
      controls; p < 0.01) but although ET-1 modulation might participate in training
      induced beneficial effects, training failed to modulate either resting or
      exercise ET-1 plasma level. Training-induced improvement in exercise capacity
      might not mainly due to decreased ET-1 after heart transplantation. Further
      supporting the usefulness of training, these preliminary data suggest that
      improved exercise capacity may not be mainly due to decreased ET-1 in Htx
      patients. Further, larger scale studies will be needed to investigate whether an
      impaired nitric oxide pathway stimulation might explain such results and whether
      a longer training program can reduce local ET-1, arising from working muscles
      after heart transplantation.

PMID- 15516243
TI  - Optimal prophylactic dosage and disposition of micafungin in living donor liver
      recipients.
AB  - Micafungin, a new candin antifungal drug, has a good safety profile and a
      significant therapeutic effect against Candida and Aspergillus. Little is known,
      however, about the optimal prophylactic dosage and the disposition of micafungin
      in liver transplant recipients, or about the effect of continuous venovenous
      hemodialysis (CVVH) on the pharmacokinetics of micafungin. Six living donor liver
      transplant patients were enrolled in this study. The mean C(max) and C(min)
      (trough) values of micafungin in plasma were 6.31 +/- 1.08 and 1.65 +/- 0.54
      microg/mL, respectively. The mean elimination half-life (t(1/2)) and mean area
      under the curve up to 12 h post-dosing (AUC 0-12 h) were 13.63 +/- 2.77 h and
      50.04 +/- 6.48 microg.h/mL, respectively. The concentrations of micafungin at the
      inlet and outlet of the dialyzer were very similar. The mean (+/-SD) ratio of
      micafungin concentrations at the inlet and outlet of the dialyzer
      (coutlet/cinlet) and the clearance of micafungin were 0.96 +/- 0.04 and 0.054 +/-
      0.04 mL/min/kg, respectively. The amount in the ultrafiltrate was 1.0 mg.
      Micafungin effectively prevents systemic fungal infection in patients who have
      undergone liver transplantation. No significant differences were observed in the
      disposition of micafungin in recipients, and the therapeutic drug level can be
      achieved by administration of micafungin at a dosage of 40-50 mg/d. The CVVH had
      little effect on micafungin kinetics, and no dose adjustment or modification of
      dosing interval was needed during CVVH.

PMID- 15516244
TI  - Living with a functioning kidney transplant at 74 yr or older: a national
      epidemiological study.
AB  - The number of older patients living with a functioning kidney graft is
      increasing. However the safety of the immunosuppressive treatment and quality of
      life in this population have not yet been determined. All patients grafted in
      France since 1969, born before the January 1 1926 and living with a functioning
      graft on January 1 2000 were included in this national study including all 34
      French transplant centers. Renal function, immunosuppressive treatment, comorbid
      conditions and quality of life were assessed. From the initial population of 446
      patients, 113 (26.2%) were still alive in 2000 (study population). Mean age was
      76 yr (range: 74-80) with a mean post-transplant follow-up of 9.9 yr (0.1-28.7).
      Average serum creatinine level was 129 micromol/L (55-286). Immunosuppression was
      heterogeneous and included triple therapy (18.6%), dual therapy (41.6%) and
      monotherapy (40.8%). A history of cancer was noted in 36 of the 113 patients
      (32.1%) whereas hypertension was the most frequent co-morbid condition (80.3%).
      Estimated quality of life using the Karnofsky scale was between 80 and 100 in
      78.4% of the patients. The immunosuppressive regimen in older renal transplant
      recipients living with a functioning graft varied widely among the 34 French
      transplant centers. Renal function in this group of patients was good and quality
      of life seemed excellent. Cardiovascular disease and malignancies were the main
      co-morbid conditions.

PMID- 15516245
TI  - Liver transplantation with preservation of the inferior vena cava. A comparison
      of conventional and piggyback techniques in adults.
AB  - The aim of this study is to analyse a single centre's experience with two
      techniques of liver transplantation (OLT), conventional (CON-OLT) and piggyback
      (PB-ES), and to compare outcome in terms of survival, morbidity, mortality and
      post-operative liver function as well as operative characteristics. A consecutive
      series (1994-2000) of 167 adult primary OLT were analysed. Ninety-six patients
      had CON-OLT and 71 patients had PB-ES. In PB-ES group two revascularization
      protocols were used. In the first protocol reperfusion of the graft was performed
      first via the portal vein followed by the arterial anastomosis (PB-seq). In the
      second protocol the graft was reperfused simultaneously via portal vein and
      hepatic artery (PB-sim). One-, 3- and 5-yr patient survival in the CON-OLT and PB
      ES groups were 90, 83 and 80%, and 83, 78 and 78%, respectively (p = ns). Graft
      survival at the same time points was 81, 73 and 69%, and 78, 69 and 65%,
      respectively (p = ns). Apart from the higher number of patients with cholangitis
      and sepsis in CON-OLT group, morbidity, retransplantation rate and post-operative
      liver and kidney function were not different between the two groups. The total
      operation time was not different between both groups (9.4 h in PB-ES vs. 10.0 h
      in CON-OLT), but in PB-ES group cold and warm ischaemia time (CIT and WIT),
      revascularization time (REVT), functional and anatomic anhepatic phases (FAHP and
      AAHP) were significantly shorter (8.9 h vs. 10.7 h, 54 min vs. 63 min, 82 min vs.
      114 min, 118 min vs. 160 min and 87 min vs. 114 min, respectively, p < 0.05). RBC
      use in the PB-ES group was lower compared to the CON-OLT group (4.0 min vs. 10.0
      units, p < 0.05). Except for WIT and REVT there were no differences in operative
      characteristics between PB-Sim and PB-Seq groups. The WIT was significantly
      longer in PB-Sim group compared with PB-Seq group (64 min vs. 50 min, p < 0.05);
      however REVT was significantly shorter in PB-Sim group (64 min vs. 97 min, p <
      0.05). Results of this study show that both techniques are comparable in survival
      and morbidity; however PB-ES results in shorter AAHP, FAHP, REVT and WIT as well
      as less RBC use. In the PB-ES group there seems to be no advantage for any of the
      revascularization protocols.

PMID- 15516246
TI  - Impact of late conversion from C0 to C2 monitoring of microemulsified
      cyclosporine in pediatric living donor liver transplant recipients.
AB  - The efficacy and feasibility of 2-h post-dose level (C2) monitoring of
      cyclosporine in long-term living donor liver transplantation (LDLT) is not clear.
      The aim of this study was to investigate the impact of late conversion from
      conventional trough-level (C0) monitoring to C2 monitoring of a microemulsion
      form of cyclosporine (Neoral) in pediatric LDLT recipients. From June 1994 to
      August 2002, we performed 116 LDLTs in 115 patients. Initially, we adapted
      conventional C0 monitoring of Neoral, which was converted to C2 monitoring
      starting in January 2002. The 60 patients who were enrolled in the study had the
      following characteristics: they were younger than or equal to 15 yr at
      transplantation, and they had survived LDLT, and they had received a Neoral-based
      immunosuppression regimen, and they underwent conversion to C2 more than 1 month
      after transplantation. We evaluated the impact of conversion on doses, blood
      levels, rejection, adverse effects, and patient/graft outcome. In the long-term
      patients, the mean C2 levels immediately after conversion were higher than the
      target levels at any time point selected after transplantation; thus, 34 patients
      (57%) finally required a dose reduction of Neoral. The current mean C2 level was
      significantly lower than that observed immediately after conversion (584.6 +/-
      262.8 ng/ml vs. 893.1 +/- 260.2 ng/ml, mean +/- SD, p < 0.0001) with a mean
      follow-up period of 7.4 +/- 0.6 months (range: 5-8 months) after conversion. Only
      one patient encountered rejection after conversion (1.7%), and no de novo
      infection or adverse effects were observed. Traditional C0 monitoring of Neoral
      was safely replaced by C2 monitoring without an increase in the rejection rate or
      any adverse effects in pediatric LDLT patients. C2 monitoring contributed to the
      dose reduction of Neoral, which may lead to the avoidance of long-term
      complications due to immunosuppression.

PMID- 15516247
TI  - Development of an unbiased method for the estimation of liver steatosis.
AB  - BACKGROUND: Steatosis significantly contributes to an organ's transplantability.
      Livers with >30% fat content have a 25% chance of developing primary non-function
      (PNF). The current practice of evaluating a hematoxylin and eosin (H&E) stained
      donor biopsy by visual interpretation is subjective. We hypothesized that H&E
      staining of frozen sections fails to accurately estimate the degree of steatosis
      present within a given liver biopsy. To address this problem of evaluating
      steatosis in prospective donor organs, we developed a fast, user friendly
      computer methodology to objectively assess fat content based on the differential
      quantification of color pixels in Oil Red O (ORO) stained liver biopsies.
      METHODS: The accuracy of human visual estimation of fat content by H&E and ORO
      stains was compared with computer-based measurements of the same slides from 25
      frozen sections of donor biopsies. RESULTS: Samples with a fat content >20%
      showed marked variation between human interpretation and computer analysis. There
      was also a significant difference in the human interpretation of fat based on the
      method of staining. This difference ranged from 3 to 37% with H&E. DISCUSSION:
      Use of ORO resulted in a more consistent estimation of liver steatosis compared
      with H&E, but human interpretations failed to correlate with computer
      measurements. Such differences in fat content estimations might result in the
      rejection of a potentially transplantable organ or the acceptance of a marginal
      one. Ideally, our protocol can rapidly be applied to clinical practice for
      accurate and consistent measurement of fat in liver sections for the ultimate
      purpose of increasing the number of successful transplantable organs.

PMID- 15516248
TI  - Knowledge and opinions about organ donation and transplantation among Vietnamese
      Americans in Seattle, Washington: a pilot study.
AB  - BACKGROUND: Racial/ethnic minorities comprise almost 50% of registrants on
      national waiting lists for organ transplantation in the USA. As the list
      continues to expand, organ shortage becomes a bigger problem. Increasing donation
      rates especially among racial minority groups would lower the waiting times for
      these groups. PURPOSE: Asian Americans are among the fastest growing and most
      diverse ethnic group in the USA, but research on their knowledge or opinions
      about organ donation is rare. POPULATION: A non-random sample of 350 Vietnamese
      American church attendees and students attending a major university in Seattle
      (Washington), was drawn. METHODS: A self-administered 39-item knowledge/opinion
      based survey was conducted during June to August 2003. RESULTS: Of 278
      respondents (a 79.7% response rate), 69.1% knew blood-type made a difference in
      donation (p = 0.000), 61.6% knew transplant survival rates were high (p = 0.000),
      and 75.9% knew transplants could come from living donors (p = 0.000). But 53.4%
      also thought organs could be sold for money in the USA (p = 0.000), and 49.8%
      thought more people died of auto accidents and gunshot wounds than from heart
      disease (p = 0.000). Those who answered correctly to more than 50% of the
      knowledge questions were also more likely to favor donation (p = 0.007).
      CONCLUSION: We found among this study population that having correct knowledge
      about organ donation related to a willingness to donate.

PMID- 15516249
TI  - Psychological effects of living related kidney transplantation - risks and
      chances.
AB  - BACKGROUND: Recipients of living donor kidney transplantation hope for an
      improved physical well-being after transplant. Furthermore the patients and their
      relatives frequently expect an improvement in their psychological findings in
      consequence of the living related transplantation. The present study examines the
      psychosocial effects of living donor kidney transplantation for donors and
      recipients under successful as well as complicated circumstances. MATERIAL AND
      METHODS: Based on 31 catamnestic interviews of recipient-donor couples and a
      content analysis of these interviews, hypotheses regarding the psychological
      requirements for a successful progression of a living kidney donation are deduced
      and put forward. RESULTS: The aspiration for an improvement of psychological
      problems, particularly anxiety and depression, as an effect of transplantation
      can on the basis of the present results not be supported. Living donor kidney
      transplantation between close recipient and donors must not be regarded as a
      means to solve psychological problems and familial conflicts. An attitude
      characterized by realistic and modest expectations as well as relationships,
      which have been cleared of extreme conflicts prior to the transplantation could
      facilitate a favourable psychological progression.

PMID- 15516250
TI  - Post-transplant C-reactive protein monitoring can predict chronic allograft
      nephropathy.
AB  - Chronic allograft nephropathy (CAN) is a major problem after renal
      transplantation and chronic inflammation can be one of its promoters. C-reactive
      protein (CRP) is an important marker of inflammation and atherosclerosis. We
      retrospectively analyzed the predictive role of serum CRP levels on the
      development of CAN and graft failure. One hundred and twenty-five renal
      transplant patients were randomly included into the study. Serum CRP levels were
      measured at pre-transplant period, first month after transplantation and at
      yearly intervals throughout follow-up. CAN was diagnosed in 40.8% of patients and
      82.4% of them had graft failure in 60.9 +/- 36.7 months. There was no difference
      at pre-transplant CRP levels of patients with and without CAN, but the first
      month CRP levels were higher in those who experienced CAN. The initial 3-yr mean
      CRP levels were higher, but not statistically different between the patients with
      and without CAN. The simultaneously detected CRP levels when CAN were diagnosed
      was significantly higher in those with CAN. High post-transplant CRP levels at
      the first month and at the diagnosis of CAN significantly influenced the
      allograft failure according to the regression analysis. CRP monitoring gives
      important information about the risk for CAN and graft failure. Therefore, CRP
      levels should be included in the follow-up data after renal transplantation.

PMID- 15516251
TI  - Clostridial infection in a liver transplant recipient.
AB  - Clostridium perfringens infection in a liver transplant recipient is a rare
      complication. We report a case of a liver allograft gas gangrene. The case
      illustrates the fulminant and rapidly devastating course of this complication.

PMID- 15516252
TI  - Accelerated rejection following offspring-to-mother and husband-to-wife
      transplants.
AB  - It has been demonstrated that graft survival rates of offspring-to-mother and
      husband-to-wife renal transplants are equivalent to those of other living donors.
      Although the vast majority of these transplants proceed without incident, we have
      encountered several instances of delayed accelerated rejections that are not
      predicted by a positive cross-match. The accelerated rejection can result from an
      anamnestic reaction subsequent to the in utero exposure of the mother to human
      leukocyte antigen (HLA) antigens of the fetus with sensitization developing
      during the pregnancy.

PMID- 15516253
TI  - Hepatic artery pseudoaneurysm - duodenal fistula after living donor liver
      transplant.
AB  - A 38-yr-old woman who underwent living donor liver transplant for alcoholic
      cirrhosis presented 2 months after transplant with gastrointestinal bleeding from
      an hepatic artery pseudoaneurysm eroding into the duodenum. She underwent
      endovascular hepatic artery stenting, resulting in cessation of hemorrhage and
      salvage of the graft.

PMID- 15516254
TI  - Successful living donor renal transplantation despite ABO incompatibility and a
      positive crossmatch.
AB  - Potential live kidney donors have been rejected when the prospective recipients
      are blood type or crossmatch incompatible. By utilizing plasmapheresis combined
      with intravenous immune globulin (PP/IVIg) prior to surgery, donor-specific
      antibodies against blood group or human leukocyte antigens (HLA) have been
      removed, thereby allowing successful renal transplantation. A 26-yr-old male with
      a panel reactive antibody level of 100% and repeated positive crossmatches
      against deceased donor kidney offers, including zero HLA mismatched donors,
      successfully underwent ABO-incompatible kidney transplantation from his HLA
      identical but nevertheless crossmatch-incompatible sister. The initial anti-A
      blood group isoagglutinin titers were 128, 256, and 1024 at room temperature, 37
      degrees C, and 37 degrees C anti-IgG enhanced, respectively. With an
      individualized PP/IVIg regimen based on donor-specific antibody titer, however,
      the relevant antibodies were adequately reduced and hyperacute rejection avoided.
      Subsequent antibody-mediated rejection, likely directed against a minor
      histocompatibility antigen, was diagnosed on postoperative day 7 and successfully
      treated. Neither ABO, or crossmatch incompatibility, or both in combination
      prohibit kidney transplantation.

PMID- 15516255
TI  - Identical reconstitution after bone marrow transplantation in twins who received
      fresh and cryopreserved grafts harvested at the same time from their older
      brother.
AB  - We report here the reconstitution after bone marrow transplantation (BMT) in
      identical infant twins with acute myelogenous leukemia (AML). They were diagnosed
      at 8 and 9 months of age. Complete remission was induced after two courses of
      chemotherapy. After four and five courses of chemotherapy, respectively, they
      received BMT at 2-month interval from the same HLA-identical older brother. The
      total dose of marrow nucleated cells (NC) harvested was 77.7 x 10(8). The first
      patient was transplanted with half of the total dose of NC. The remaining cells
      were cryopreserved without the use of a programmed freezer and transplanted into
      the second patient 2 months later. The number of days for neutrophil (>0.5 x
      10(9)/L), platelet (>50 x 10(9)/L), and reticulocyte (>1%) recovery were,
      respectively, 15, 21, and 14 in the first case and 12, 21, and 15 in the second
      case. The clinical courses after BMT were uneventful in both cases, except for
      mild acute GVHD, and complete remission has been maintained >4 yr with full
      recovery of immune and marrow function. Based on the results in these cases, we
      confirmed that marrow cells that have been cryopreserved without the use of a
      programmed freezer could reconstitute immune and marrow function as well as non
      cryopreserved cells.

PMID- 15516256
TI  - Rhodococcus equi pneumonia in a renal transplant patient: a case report and
      review of literature.
AB  - Immunocompromised patients are susceptible to many pathogens, including those
      that are predominantly problems in veterinary medicine. We report a case of a 42
      yr-old white male who presented 19 months post-cadaveric renal transplant (for
      IgA nephropathy) with a 5 d history of nausea, vomiting, abdominal cramping and
      diarrhea. Admission chest X-ray revealed a suspicious mass lesion in the left
      lower lobe. Computed tomography (CT) guided biopsy of the lesion showed a large
      zone of CD68 +ve histiocytes in a non-caseating granuloma. Gram stain revealed
      multiple gram-positive rods within the histiocytes, which were eventually
      identified as R. equi. After 4 months of therapy with fluoroquinolones (Avelox)
      and Azithromycin a repeat CT showed complete resolution of the lesion. We
      reviewed the literature with special focus on the clinical features, challenges
      in diagnosis, and treatment of this rare infection (especially in the transplant
      patients who are also on immunosuppressive therapy).

PMID- 15516257
TI  - West Nile virus encephalitis: an emerging disease in renal transplant recipients.
AB  - West Nile virus (WNV) has emerged as an important cause of several outbreaks of
      febrile illness and encephalitis in North America over the past few years. The
      most common manifestation in symptomatic patients is a transient febrile illness.
      Neuroinvasive disease, that can be fatal, occurs most often in elderly and
      immunocompromised hosts. The role of this virus as a cause of meninoencephalitis
      in organ transplant recipients is becoming better recognized. We describe herein
      the clinical course of two renal allograft recipients who developed WNV
      encephalitis. One patient developed status epilepticus and eventually died, while
      the other had a full recovery. In both cases, the diagnosis was confirmed by
      detection of WNV-specific IgM in CSF or serum, with a delayed antibody response
      in one patient. This viral infection should be considered in all renal transplant
      recipients who present with a febrile illness associated with neurological
      symptoms.

PMID- 15516258
TI  - Campath and renal transplant rejection.
AB  - No clear guidelines exist for the treatment of acute vascular rejection following
      renal transplantation. This report documents one patient who was treated with
      plasmapheresis, immunoglobulin and Campath with good initial response. However,
      rejection recurred resulting in graft loss and, in addition, the patient
      developed post-transplant lymphoma.

PMID- 15516259
TI  - Spinal epidural lipomatosis following haploidentical allogeneic bone marrow
      transplantation for non-Hodgkin lymphoma.
AB  - OBJECTIVES: Spinal epidural lipomatosis, is a very rare condition, usually seen
      as an uncommon complication of Cushing's syndrome secondary to chronic steroid
      therapy leading to increased fat deposits in the epidural space. CASE REPORT: We
      report the first documented case of acute symptomatic spinal epidural lipomatosis
      in a patient with relapsed non-Hodgkin lymphoma. The patient underwent an
      allogeneic bone marrow transplantation (BMT) and a month of steroid treatment for
      acute graft vs. host disease (GvHD). He presented with a mild to moderate
      Cushing's syndrome and minimal obesity. He progressed rapidly to paraparesis,
      sensory deficit, urinary incontinence and finally respiratory arrest complicated
      with staphylococcal sepsis. CONCLUSION: Epidural lipomatosis, with subacute
      thecal sac compression, is a possible life-threatening complication of relatively
      short-term systemic glucocorticoid therapy for GvHD in BMT setting.

PMID- 15516260
TI  - The InDeVal insertion/deletion evaluation tool: a program for finding target
      regions in DNA sequences and for aiding in sequence comparison.
AB  - BACKGROUND: The program InDeVal was originally developed to help researchers find
      known regions of insertion/deletion activity (with the exception of isolated
      single-base indels) in newly determined Poaceae trnL-F sequences and compare them
      with 533 previously determined sequences. It is supplied with input files
      designed for this purpose. More broadly, the program is applicable for finding
      specific target regions (referred to as "variable regions") in DNA sequence. A
      variable region is any specific sequence fragment of interest, such as an indel
      region, a codon or codons, or sequence coding for a particular RNA secondary
      structure. RESULTS: InDeVal input is DNA sequence and a template file (sequence
      flanking each variable region). Additional files contain the variable regions and
      user-defined messages about the sequence found within them (e.g., taxa sharing
      each of the different indel patterns).Variable regions are found by determining
      the position of flanking sequence (referred to as "conserved regions") using the
      LPAM (Length-Preserving Alignment Method) algorithm. This algorithm was designed
      for InDeVal and is described here for the first time. InDeVal output is an
      interactive display of the analyzed sequence, broken into user-defined units.
      Once the user is satisfied with the organization of the display, the information
      can be exported to an annotated text file. CONCLUSIONS: InDeVal can find multiple
      variable regions simultaneously (28 indel regions in the Poaceae trnL-F files)
      and display user-selected messages specific to the sequence variants found.
      InDeVal output is designed to facilitate comparison between the analyzed sequence
      and previously evaluated sequence. The program's sensitivity to different levels
      of nucleotide and/or length variation in conserved regions can be adjusted.
      InDeVal is currently available for Windows in Additional file 1 or from
      http://www.sci.muni.cz/botany/elzdroje/indeval/.

PMID- 15516261
TI  - Physical function and associations with diet and exercise: Results of a cross
      sectional survey among elders with breast or prostate cancer.
AB  - BACKGROUND: Functional decline threatens independent living and is common among
      individuals diagnosed with cancer, especially those who are elderly. The purpose
      of this study was to explore whether dietary and exercise practices are
      associated with physical function status among older cancer survivors. METHODS:
      Mailed surveys were used to ascertain data on physical function, dietary fat,
      fruit and vegetable (F&V) consumption, and exercise among elderly diagnosed with
      early stage (I-II) breast (N = 286) or prostate cancer (N = 402) within the past
      18 months. RESULTS: Sixty-one percent of respondents reported diets with <30% of
      energy from fat, 20.4% reported F&V intakes of 5+ daily servings, and 44.6%
      reported regular vigorous exercise. Significant, independent associations were
      found between physical functioning and reported dietary fat intake, F&V
      consumption, and exercise. A simultaneous multiple regression model controlled
      for age, race, gender, time since diagnosis and concurrent health behaviors
      yielded the following estimates: (1) 0.2 increase in the SF-36 physical function
      subscale (PFS) score with each reported 1% decrease in percent energy from fat (p
      < .0001); (2) 0.9 increase in the SF-36 PFS score for each reported serving of
      F&V/day (p = .0049); and (3) 15.4 increase in the SF-36 PFS score with a positive
      response for regular vigorous exercise (p < .0001). CONCLUSIONS: Results of this
      cross-sectional survey suggest that regular vigorous exercise and consumption of
      diets low in fat and rich in F&Vs are associated with higher levels of physical
      functioning among older cancer survivors. Interventions that promote healthful
      lifestyle change may deliver considerable benefit within this ever increasing and
      vulnerable population.

PMID- 15516262
TI  - Comparative evaluation of diode laser versus argon laser photocoagulation in
      patients with central serous retinopathy: a pilot, randomized controlled trial
      [ISRCTN84128484].
AB  - BACKGROUND: To evaluate the efficacy of diode laser photocoagulation in patients
      with central serous retinopathy (CSR) and to compare it with the effects of argon
      green laser. METHODS: Thirty patients with type 1 unilateral CSR were enrolled
      and evaluated on parameters like best corrected visual acuity (BCVA), direct and
      indirect ophthalmoscopy, amsler grid for recording scotoma and metamorphopsia,
      contrast sensitivity using Cambridge low contrast gratings and fluorescein
      angiography to determine the site of leakage. Patients were randomly assigned
      into 2 groups according to the statistical random table using sequence
      generation. In Group 1 (n = 15), diode laser (810 nm) photocoagulation was
      performed at the site of leakage while in Group 2 (n = 15), eyes were treated
      with argon green laser (514 nm) using the same laser parameters. Patients were
      followed up at 4, 8 and 12 weeks after laser. RESULTS: The mean BCVA in group 1
      improved from a pre-laser decimal value of 0.29 +/- 0.14 to 0.84 +/- 0.23 at 4
      weeks and 1.06 +/- 0.09 at 12 weeks following laser. In group 2, the same
      improved from 0.32 +/- 0.16 to 0.67 +/- 0.18 at 4 weeks and 0.98 +/- 0.14 at 12
      weeks following laser. The improvement in BCVA was significantly better in group
      1 (p < 0.0001) at 4 weeks. At 4 weeks following laser, all the patients in group1
      were free of scotoma while 6 patients in group 2 had residual scotoma (p < 0.05).
      The mean contrast sensitivity in group 1 improved from pre-laser value of 98.4 +/
      24.77 to 231.33 +/- 48.97 at 4 weeks and 306.00 +/- 46.57 at 12 weeks following
      laser. In group 2, the same improved from 130.66 +/- 31.95 to 190.66 +/- 23.44 at
      4 weeks and 215.33 +/- 23.25 at 12 weeks. On comparative evaluation, a
      significantly better (p < 0.001) improvement was noted in group 1. CONCLUSION:
      Diode laser may be a better alternative to argon green laser whenever laser
      treatment becomes indicated in patients with central serous retinopathy in terms
      of faster visual rehabilitation and better contrast sensitivity. In addition,
      diode laser also has the well-recognized ergonomic and economic advantages.

PMID- 15516263
TI  - Traumatic-event headaches.
AB  - BACKGROUND: Chronic headaches from head trauma and whiplash injury are well-known
      and common, but chronic headaches from other sorts of physical traumas are not
      recognized. METHODS: Specific information was obtained from the medical records
      of 15 consecutive patients with chronic headaches related to physically injurious
      traumatic events that did not include either head trauma or whiplash injury. The
      events and the physical injuries produced by them were noted. The headaches'
      development, characteristics, duration, frequency, and accompaniments were
      recorded, as were the patients' use of pain-alleviative drugs. From this latter
      information, the headaches were classified by the diagnostic criteria of the
      International Headache Society as though they were naturally-occurring headaches.
      The presence of other post-traumatic symptoms and litigation were also recorded.
      RESULTS: The intervals between the events and the onset of the headaches
      resembled those between head traumas or whiplash injuries and their subsequent
      headaches. The headaches themselves were, as a group, similar to those after head
      trauma and whiplash injury. Thirteen of the patients had chronic tension-type
      headache, two had migraine. The sustained bodily injuries were trivial or
      unidentifiable in nine patients. Fabrication of symptoms for financial
      remuneration was not evident in these patients of whom seven were not even
      seeking payments of any kind. CONCLUSIONS: This study suggests that these
      hitherto unrecognized post-traumatic headaches constitute a class of headaches
      characterized by a relation to traumatic events affecting the body but not
      including head or whiplash traumas. The bodily injuries per se can be discounted
      as the cause of the headaches. So can fabrication of symptoms for financial
      remuneration. Altered mental states, not systematically evaluated here, were a
      possible cause of the headaches. The overall resemblance of these headaches to
      the headaches after head or whiplash traumas implies that these latter two
      headache types may likewise not be products of structural injuries.

PMID- 15516264
TI  - Gel shift analysis of the empA promoter region in Vibrio anguillarum.
AB  - BACKGROUND: The induction of metalloprotease encoded by empA in Vibrio
      anguillarum occurs at high cell density in salmon intestinal mucus. Previously we
      have shown that there are significant differences in empA expression in two
      strains of V. anguillarum, M93Sm and NB10. It is hypothesized that differences in
      empA regulation are due to differences in binding of regulatory elements.
      RESULTS: Two strains of V. anguillarum, M93Sm and NB10, were examined and
      compared for the presence of DNA regulatory proteins that bind to and control the
      empA promoter region. Gel mobility shift assays, using a digoxigenin (DIG)
      labeled oligomer containing a lux box-like element and the promoter for empA,
      were done to demonstrate the presence of a DNA-binding protein. Protein extracts
      from NB10 cells incubated in Luria Bertani broth + 2% NaCl (LB20), nine salts
      solution + 200 microg/ml mucus (NSSM), 3M (marine minimal medium), or NSS
      resulted in a gel mobility shift. No gel mobility shift was seen when protein
      extracts from either LB20- or NSSM-grown M93Sm cells were mixed with the DIG
      labeled empA oligomer. The azocasein assay detected protease activity in all
      incubation conditions for NB10 culture supernatants. In contrast, protease
      activity was detected in M93Sm culture supernatants only when incubated in NSSM.
      Since the luxR homologue in V. anguillarum, vanT, has been cloned, sequenced, and
      shown to be required for protease activity, we wanted to determine if vanT
      mutants of NB10 exhibit the same gel shift observed in the wild-type. Site
      directed mutagenesis was used to create vanT mutants in V. anguillarum M93Sm and
      NB10 to test whether VanT is involved with the gel mobility shift. Both vanT
      mutants, M02 and NB02, did not produce protease activity in any conditions.
      However, protein extracts from NB02 incubated in each condition still exhibited a
      gel shift when mixed with the DIG-labeled empA oligomer. CONCLUSIONS: The data
      demonstrate that protein extracts of V. anguillarum NB10 cells contain a protein
      that binds to a 50 bp oligomer containing the empA promoter-lux box-like region.
      NB10 cells express empA during stationary phase in all growth conditions. The DNA
      binding protein is not present in M93Sm extracts. M93Sm cells express protease
      activity only when incubated at high cell density in fish gastrointestinal mucus.
      The gel shift observed with NB10 cells is not due to VanT binding. The data also
      suggest that the DNA binding protein is responsible for the less restrictive
      expression of empA in NB10 compared to M93Sm.

PMID- 15516265
TI  - The Drosophila methyl-DNA binding protein MBD2/3 interacts with the NuRD complex
      via p55 and MI-2.
AB  - BACKGROUND: Methyl-DNA binding proteins help to translate epigenetic information
      encoded by DNA methylation into covalent histone modifications. MBD2/3 is the
      only candidate gene in the Drosophila genome with extended homologies to
      mammalian MBD2 and MBD3 proteins, which represent a co-repressor and an integral
      component of the Nucleosome Remodelling and Deacetylase (NuRD) complex,
      respectively. An association of Drosophila MBD2/3 with the Drosophila NuRD
      complex has been suggested previously. We have now analyzed the molecular
      interactions between MBD2/3 and the NuRD complex in greater detail. RESULTS: The
      two MBD2/3 isoforms precisely cofractionated with NuRD proteins during gel
      filtration of extracts derived from early and late embryos. In addition, we
      demonstrate that MBD2/3 forms multimers, and engages in specific interactions
      with the p55 and MI-2 subunits of the Drosophila NuRD complex. CONCLUSION: Our
      data provide novel insights into the association between Drosophila MBD2/3 and
      NuRD proteins. Additionally, this work provides a first analysis of the
      architecture of the Drosophila NuRD complex.

PMID- 15516266
TI  - Within you, without you: HIV-1 Rev and RNA export.
AB  - Nucleo-cytoplasmic transport of RNA is one of many cellular pathways whose
      illumination has progressed hand in hand with understanding of retroviral
      mechanisms. A recent paper in Cell reports the involvement of an RNA helicase in
      the pathway by which HIV exports partially spliced and unspliced RNA out of the
      nucleus. This suggests the ubiquity of RNA helicases in RNA export from the
      nucleus, and has novel mechanistic implications.

PMID- 15516267
TI  - Mucosal delivery of anti-inflammatory IL-1Ra by sporulating recombinant bacteria.
AB  - BACKGROUND: Mucosal delivery of therapeutic protein drugs or vaccines is actively
      investigated, in order to improve bioavailability and avoid side effects
      associated with systemic administration. Orally administered bacteria, engineered
      to produce anti-inflammatory cytokines (IL-10, IL-1Ra), have shown localised
      ameliorating effects in inflammatory gastro-intestinal conditions. However, the
      possible systemic effects of mucosally delivered recombinant bacteria have not
      been investigated. RESULTS: B. subtilis was engineered to produce the mature
      human IL-1 receptor antagonist (IL-1Ra). When recombinant B. subtilis was
      instilled in the distal colon of rats or rabbits, human IL-1Ra was found both in
      the intestinal lavage and in the serum of treated animals. The IL-1Ra protein in
      serum was intact and biologically active. IL-1-induced fever, neutrophilia,
      hypoglycemia and hypoferremia were inhibited in a dose-dependent fashion by intra
      colon administration of IL-1Ra-producing B. subtilis. In the mouse, intra
      peritoneal treatment with recombinant B. subtilis could inhibit endotoxin-induced
      shock and death. Instillation in the rabbit colon of another recombinant B.
      subtilis strain, which releases bioactive human recombinant IL-1beta upon
      autolysis, could induce fever and eventually death, similarly to parenteral
      administration of high doses of IL-1beta. CONCLUSIONS: A novel system of
      controlled release of pharmacologically active proteins is described, which
      exploits bacterial autolysis in a non-permissive environment. Mucosal
      administration of recombinant B. subtilis causes the release of cytoplasmic
      recombinant proteins, which can then be found in serum and exert their biological
      activity in vivo systemically.

PMID- 15516269
TI  - Improving the accuracy of malaria-related laboratory tests in Ghana.
AB  - BACKGROUND: Inaccurate malaria results can lead to patient mismanagement,
      misperceptions about malaria resistance patterns and public health
      misinformation. All laboratories need to be able to demonstrate that their
      results are accurate. Establishing and maintaining a system for monitoring test
      accuracy is a complex, expensive and technically demanding process, which very
      few poor countries have been able to implement. This study described the process
      and assessed the feasibility of establishing a nation-wide system for improving
      the accuracy of malaria-related tests in peripheral laboratories in Ghana.
      PROGRAMME IMPLEMENTATION: A baseline survey of all 693 laboratory staff in 205
      sub-regional government and mission health laboratories in Ghana was conducted by
      a national network of laboratory supervisors. Survey results guided a training
      programme to improve test accuracy. Outcomes included changes in the quality of
      laboratory tests and the system was considered to be feasible if >50% of
      laboratory staff in each region received training and if test accuracy could be
      documented. PROGRAMME INDICATORS: 74% (mean) of the 693 laboratory staff were
      assistants with no professional qualifications. There were marked differences
      between regions in the availability of essential resources for malaria diagnosis
      (e.g. microscopes). 93% of laboratory staff received training; in six months
      there were increases of 11% and 7% respectively in the number of laboratories
      producing haemoglobin and malaria microscopy results of acceptable quality.
      CONCLUSIONS: It is possible to establish a system for improving and monitoring
      test accuracy in peripheral laboratories on a country-wide basis in a developing
      country using a model that could be adapted for use in other countries and for
      other components of health care provision.

PMID- 15516268
TI  - Pudendal nerve decompression in perineology: a case series.
AB  - BACKGROUND: Perineodynia (vulvodynia, perineal pain, proctalgia), anal and
      urinary incontinence are the main symptoms of the pudendal canal syndrome (PCS)
      or entrapment of the pudendal nerve. The first aim of this study was to evaluate
      the effect of bilateral pudendal nerve decompression (PND) on the symptoms of the
      PCS, on three clinical signs (abnormal sensibility, painful Alcock's canal,
      painful "skin rolling test") and on two neurophysiological tests:
      electromyography (EMG) and pudendal nerve terminal motor latencies (PNTML). The
      second aim was to study the clinical value of the aforementioned clinical signs
      in the diagnosis of PCS. METHODS: In this retrospective analysis, the studied
      sample comprised 74 female patients who underwent a bilateral PND between 1995
      and 2002. To accomplish the first aim, the patients sample was compared before
      and at least one year after surgery by means of descriptive statistics and
      hypothesis testing. The second aim was achieved by means of a statistical
      comparison between the patient's group before the operation and a control group
      of 82 women without any of the following signs: prolapse, anal incontinence,
      perineodynia, dyschesia and history of pelvi-perineal surgery. RESULTS: When
      bilateral PND was the only procedure done to treat the symptoms, the cure rates
      of perineodynia, anal incontinence and urinary incontinence were 8/14, 4/5 and
      3/5, respectively. The frequency of the three clinical signs was significantly
      reduced. There was a significant reduction of anal and perineal PNTML and a
      significant increase of anal richness on EMG. The Odd Ratio of the three clinical
      signs in the diagnosis of PCS was 16,97 (95% CI = 4,68 - 61,51). CONCLUSION: This
      study suggests that bilateral PND can treat perineodynia, anal and urinary
      incontinence. The three clinical signs of PCS seem to be efficient to suspect
      this diagnosis. There is a need for further studies to confirm these preliminary
      results.

PMID- 15516270
TI  - SIVdrl detection in captive mandrills: are mandrills infected with a third strain
      of simian immunodeficiency virus?
AB  - A pol-fragment of simian immunodeficiency virus (SIV) that is highly related to
      SIVdrl-pol from drill monkeys (Mandrillus leucophaeus) was detected in two
      mandrills (Mandrillus sphinx) from Amsterdam Zoo. These captivity-born mandrills
      had never been in contact with drill monkeys, and were unlikely to be hybrids.
      Their mitochondrial haplotype suggested that they descended from founder animals
      in Cameroon or northern Gabon, close to the habitat of the drill. SIVdrl has once
      before been found in a wild-caught mandrill from the same region, indicating that
      mandrills are naturally infected with a SIVdrl-like virus. This suggests that
      mandrills are the first primate species to be infected with three strains of SIV:
      SIVmnd1, SIVmnd2, and SIVdrl.

PMID- 15516271
TI  - How many clusters? An information-theoretic perspective.
AB  - Clustering provides a common means of identifying structure in complex data, and
      there is renewed interest in clustering as a tool for the analysis of large data
      sets in many fields. A natural question is how many clusters are appropriate for
      the description of a given system. Traditional approaches to this problem are
      based on either a framework in which clusters of a particular shape are assumed
      as a model of the system or on a two-step procedure in which a clustering
      criterion determines the optimal assignments for a given number of clusters and a
      separate criterion measures the goodness of the classification to determine the
      number of clusters. In a statistical mechanics approach, clustering can be seen
      as a trade-off between energy- and entropy-like terms, with lower temperature
      driving the proliferation of clusters to provide a more detailed description of
      the data. For finite data sets, we expect that there is a limit to the meaningful
      structure that can be resolved and therefore a minimum temperature beyond which
      we will capture sampling noise. This suggests that correcting the clustering
      criterion for the bias that arises due to sampling errors will allow us to find a
      clustering solution at a temperature that is optimal in the sense that we capture
      maximal meaningful structure--without having to define an external criterion for
      the goodness or stability of the clustering. We show that in a general
      information-theoretic framework, the finite size of a data set determines an
      optimal temperature, and we introduce a method for finding the maximal number of
      clusters that can be resolved from the data in the hard clustering limit.

PMID- 15516272
TI  - A learning rule for local synaptic interactions between excitation and shunting
      inhibition.
AB  - The basic requirement for direction selectivity is a nonlinear interaction
      between two different inputs in space-time. In some models, the interaction is
      hypothesized to occur between excitation and inhibition of the shunting type in
      the neuron's dendritic tree. How can the required spatial specificity be acquired
      in an unsupervised manner? We here propose an activity-based, local learning
      model that can account for direction selectivity in visual cortex based on such a
      local veto operation and that depends on synaptically induced changes in
      intracellular calcium concentration. Our biophysical simulations suggest that a
      model cell with our learning algorithm can develop direction selectivity
      organically after unsupervised training. The learning rule is also applicable to
      a neuron with multiple-direction-selective subunits and to a pair of cells with
      opposite-direction selectivities and is stable under different starting
      conditions, delays, and velocities.

PMID- 15516273
TI  - Maximum likelihood estimation of a stochastic integrate-and-fire neural encoding
      model.
AB  - We examine a cascade encoding model for neural response in which a linear
      filtering stage is followed by a noisy, leaky, integrate-and-fire spike
      generation mechanism. This model provides a biophysically more realistic
      alternative to models based on Poisson (memoryless) spike generation, and can
      effectively reproduce a variety of spiking behaviors seen in vivo. We describe
      the maximum likelihood estimator for the model parameters, given only
      extracellular spike train responses (not intracellular voltage data).
      Specifically, we prove that the log-likelihood function is concave and thus has
      an essentially unique global maximum that can be found using gradient ascent
      techniques. We develop an efficient algorithm for computing the maximum
      likelihood solution, demonstrate the effectiveness of the resulting estimator
      with numerical simulations, and discuss a method of testing the model's validity
      using time-rescaling and density evolution techniques.

PMID- 15516274
TI  - Image representation by complex cell responses.
AB  - We present an analysis of the representation of images as the magnitudes of their
      transform with complex-valued Gabor wavelets. Such a representation is a model
      for complex cells in the early stage of visual processing and of high technical
      usefulness for image understanding, because it makes the representation
      insensitive to small local shifts. We show that if the images are band limited
      and of zero mean, then reconstruction from the magnitudes is unique up to the
      sign for almost all images.

PMID- 15516275
TI  - Mean field and capacity in realistic networks of spiking neurons storing sparsely
      coded random memories.
AB  - Mean-field (MF) theory is extended to realistic networks of spiking neurons
      storing in synaptic couplings of randomly chosen stimuli of a given low coding
      level. The underlying synaptic matrix is the result of a generic, slow, long-term
      synaptic plasticity of two-state synapses, upon repeated presentation of the
      fixed set of the stimuli to be stored. The neural populations subtending the MF
      description are classified by the number of stimuli to which their neurons are
      responsive (multiplicity). This involves 2p + 1 populations for a network storing
      p memories. The computational complexity of the MF description is then
      significantly reduced by observing that at low coding levels (f), only a few
      populations remain relevant: the population of mean multiplicity - pf and those
      of multiplicity of order square root pf around the mean. The theory is used to
      produce (predict) bifurcation diagrams (the onset of selective delay activity and
      the rates in its various stationary states) and to compute the storage capacity
      of the network (the maximal number of single items used in training for each of
      which the network can sustain a persistent, selective activity state). This is
      done in various regions of the space of constitutive parameters for the neurons
      and for the learning process. The capacity is computed in MF versus potentiation
      amplitude, ratio of potentiation to depression probability and coding level f.
      The MF results compare well with recordings of delay activity rate distributions
      in simulations of the underlying microscopic network of 10,000 neurons.

PMID- 15516276
TI  - Canonical correlation analysis: an overview with application to learning methods.
AB  - We present a general method using kernel canonical correlation analysis to learn
      a semantic representation to web images and their associated text. The semantic
      space provides a common representation and enables a comparison between the text
      and images. In the experiments, we look at two approaches of retrieving images
      based on only their content from a text query. We compare orthogonalization
      approaches against a standard cross-representation retrieval technique known as
      the generalized vector space model.

PMID- 15516277
TI  - Cognitive map formation through sequence encoding by theta phase precession.
AB  - The rodent hippocampus has been thought to represent the spatial environment as a
      cognitive map. The associative connections in the hippocampus imply that a neural
      entity represents the map as a geometrical network of hippocampal cells in terms
      of a chart. According to recent experimental observations, the cells fire
      successively relative to the theta oscillation of the local field potential,
      called theta phase precession, when the animal is running. This observation
      suggests the learning of temporal sequences with asymmetric connections in the
      hippocampus, but it also gives rather inconsistent implications on the formation
      of the chart that should consist of symmetric connections for space coding. In
      this study, we hypothesize that the chart is generated with theta phase coding
      through the integration of asymmetric connections. Our computer experiments use a
      hippocampal network model to demonstrate that a geometrical network is formed
      through running experiences in a few minutes. Asymmetric connections are found to
      remain and distribute heterogeneously in the network. The obtained network
      exhibits the spatial localization of activities at each instance as the chart
      does and their propagation that represents behavioral motions with
      multidirectional properties. We conclude that theta phase precession and the
      Hebbian rule with a time delay can provide the neural principles for learning the
      cognitive map.

PMID- 15516278
TI  - A complex-valued RTRL algorithm for recurrent neural networks.
AB  - A complex-valued real-time recurrent learning (CRTRL) algorithm for the class of
      nonlinear adaptive filters realized as fully connected recurrent neural networks
      is introduced. The proposed CRTRL is derived for a general complex activation
      function of a neuron, which makes it suitable for nonlinear adaptive filtering of
      complex-valued nonlinear and nonstationary signals and complex signals with
      strong component correlations. In addition, this algorithm is generic and
      represents a natural extension of the real-valued RTRL. Simulations on benchmark
      and real-world complex-valued signals support the approach.

PMID- 15516279
TI  - A survey on high-concentration-capability headspace sampling techniques in the
      analysis of flavors and fragrances.
AB  - This survey critically discusses high-concentration-capacity (HCC) headspace (HS)
      techniques applied to sample the volatile fraction of matrices of interest in the
      flavors and fragrance fields. In particular, the advantages, limits, and fields
      of application of HS solid-phase microextraction (SPME), high-capacity HS
      sorptive extraction (HSSE) and HS solid-phase dynamic extraction (SPDE) are
      evaluated. These techniques are discussed in view of the peculiar characteristic
      of HCC-HS techniques, from the standpoint that these techniques are a bridge
      between static (S-HS) and dynamic HS (D-HS) because they are as simple, fast,
      easy to automate, and reliable as S-HS, yet afford analyte concentration factors
      comparable to those of D-HS. Moreover, the different degree of their development
      is a consequence of the different times in which they were introduced into the
      market, because the potential of HS-SPME is now well known, having been
      introduced approximately 12 years ago, but that of HSSE has still to be fully
      explored, and HS-SPDE still has to be investigated because it is very recent.

PMID- 15516280
TI  - Fast GC for the analysis of citrus oils.
AB  - In this investigation, the gas chromatographic (GC) analysis of citrus essential
      oils is carried out in 3.3 min, with a speed gain of almost 14 times in
      comparison with traditional GC procedures. The fast method that is developed
      requires the application of severe experimental conditions (accelerated
      temperature program rates, high inlet pressures, and split ratios) and, thus, the
      support of adequate instrumentation. The samples investigated can be considered
      to be rather complex and, although a slight loss in peak resolution is observed,
      the overall analytical result is excellent. All data obtained are compared with
      that of a conventional application on the same matrices. This is done in order to
      evaluate the effectiveness and advantages of fast GC achieved with narrow bore
      columns.

PMID- 15516281
TI  - Comprehensive two-dimensional gas chromatography with flame ionization and time
      of-flight mass spectrometry detection: qualitative and quantitative analysis of
      West Australian sandalwood oil.
AB  - The use of gas chromatography (GC)-mass spectrometry (MS), GC-time-of-flight MS
      (TOFMS), comprehensive two-dimensional GC (GCxGC)-flame ionization detection
      (FID), and GCxGC-TOFMS is discussed for the characterization of the eight
      important representative components, including Z-alpha-santalol, epi-alpha
      bisabolol, Z-alpha-trans-bergamotol, epi-beta-santalol, Z-beta-santalol, E,E
      farnesol, Z-nuciferol, and Z-lanceol, in the oil of west Australian sandalwood
      (Santalum spicatum). Single-column GC-MS lacks the resolving power to separate
      all of the listed components as pure peaks and allow precise analytical
      measurement of individual component abundances. With enhanced peak resolution
      capabilities in GCxGC, these components are sufficiently well resolved to be
      quantitated using flame ionization detection, following initial characterization
      of components by using GCxGC-TOFMS.

PMID- 15516282
TI  - Enantioselective gas chromatography in flavor and fragrance analysis: strategies
      for the identification of known and unknown plant volatiles.
AB  - This review describes current analytical technology for the analysis of chiral
      constituents in essential oils and other natural volatiles, flavor and fragrance
      compounds, and covers some important results achieved by natural compound
      chemists, food chemists, perfumers, and molecular biologists. The technique of
      enantioselective gas chromatography (GC) is described and applied for assigning
      absolute configuration of chiral natural compounds, which is strongly connected
      to differences in odor properties of their enantiomers. In addition, some recent
      results to facilitate the handling of GC-mass spectrometry data of known and
      unknown plant volatiles are discussed.

PMID- 15516283
TI  - Authenticity assessment: a permanent challenge in food flavor and essential oil
      analysis.
AB  - Both phenomena, enantioselectivity as well as isotope discrimination during
      biosynthesis, may serve as "endogenous" parameters, provided that suitable
      methods and comprehensive data from authentic sources are available. This review
      reports on enantioselective capillary gas chromatography and online methods of
      isotope-ratio mass spectrometry in the authentication of food flavor and
      essential oil compounds, referring to literature references published in the last
      decade.

PMID- 15516284
TI  - Hyphenation of quadrupole MS to GC and comprehensive two-dimensional GC for the
      analysis of suspected allergens: review and improvement.
AB  - This survey reviews papers that have been previously published on the
      quantitative analysis of suspected allergens. The routine gas chromatography (GC)
      mass spectrometry (MS) method allows their evaluation in most fragrances, but the
      application of an automated data treatment sometimes leads to over- or
      underestimations when target compounds are coeluted or shifted because of the
      presence of other fragrance ingredients. In such cases, an appropriate
      retreatment of data generated by the routine analysis is proposed to better
      estimate these shifted or coeluted peaks. A second and more sophisticated
      approach, based on comprehensive bidimensional GC hyphenated to quadrupole MS,
      overcomes coelution problems. However, its use is still time consuming because of
      the lack of a commercial program. In this work, a software prototype is tested to
      reprocess the data. It dramatically shortens the data treatment and offers good
      quantitative results.

PMID- 15516285
TI  - Relationship of Delta 9-tetrahydrocannabinol concentrations in oral fluid and
      plasma after controlled administration of smoked cannabis.
AB  - Understanding the relationship of Delta(9)-tetrahydrocannabinol (THC)
      concentrations in oral fluid and plasma is important in interpretation of oral
      fluid test results. Current evidence suggests that THC is deposited in the oral
      cavity during cannabis smoking. This "depot" represents the primary or sole
      source of THC found when oral fluid is collected and analyzed. In this research,
      oral fluid and plasma specimens were collected from six subjects following
      smoking of cannabis cigarettes containing 1.75% and 3.55% THC. There was at least
      one week between each cannabis administration. Plasma specimens were analyzed by
      gas chromatography-mass spectrometry (GC-MS) and paired oral fluid specimens were
      analyzed by radioimmunoassay (RIA). In addition, one individual's oral fluid
      specimens were also analyzed by GC-MS. These data are unique in that they
      represent simultaneous or near simultaneous collection of oral fluid and plasma
      specimens in subjects following controlled cannabis dosing. The first oral fluid
      specimen, collected from one subject at 0.2 h following initiation of smoking,
      contained a THC concentration of 5800 ng/mL (GC-MS). By 0.33 h, the THC
      concentration in oral fluid had fallen to 81 ng/mL. From approximately 0.3 h
      through 4.0 h, the mean (+/- SD) THC ratio of oral fluid to plasma THC
      concentrations was 1.18 (0.62) with a range of 0.5 to 2.2. Within 12 h, both oral
      fluid and plasma THC concentrations generally declined below 1 ng/mL. RIA
      analyses of oral fluid specimens for six subjects demonstrated the same pattern
      of initial high levels of contamination immediately after smoking, followed by
      rapid clearing, and a slower decline over 12 h. Mean THC oral fluid
      concentrations by RIA at 0.2 h were 864 ng/mL and 4167 ng/mL compared to plasma
      concentrations of 52 ng/mL and 230 ng/mL at 0.27 h following the low- and high
      dose cannabis cigarettes, respectively. The similarity in oral fluid and plasma
      THC concentrations following the dissipation of the initial "contamination"
      indicates the likelihood of a physiological link between these specimens. Recent
      studies have shown that sublingual or transmucosal administration of pure THC
      results in direct absorption of intact THC into the bloodstream, thereby
      bypassing the gastrointestinal tract. The current study demonstrates that THC is
      deposited in the oral cavity and remains for up to 24 h following cannabis
      smoking. The decline in THC oral fluid concentration over this time suggests that
      there may be absorption of THC into blood as previously shown with pure THC.
      Passive cannabis exposure studies appear to indicate that positive oral fluid
      tests for THC can occur shortly after cannabis smoke exposure, but results were
      negative within 1 h. Consequently, when very recent passive exposure to cannabis
      smoke can be ruled out, it is concluded that a positive oral fluid test provides
      credible evidence of active cannabis use.

PMID- 15516286
TI  - Development of an analytical approach to the specimens collected from victims of
      sexual assault.
AB  - The objective of this study was to develop a screening process for the analysis
      of sexual assault samples. Recently, the Society of Forensic Toxicologists
      created a committee to address the issue of drug-facilitated sexual assault
      (DFSA) in the toxicology field. This committee prepared a list of drugs that
      could be, or have been, used in DFSAs. The list comprises about 50 compounds,
      including illicit, prescription, and over-the-counter drugs. Using this list, our
      laboratory wanted an easy, fast, and sensitive method to analyze a urine sample
      for all 50 of these drugs. We screened and confirmed for 20 compounds, including
      cocaine, amphetamines, benzodiazepines, barbiturates, opiates, methadone,
      alcohol, and PCP. A gas chromatographic-mass spectrometric screening method that
      was able to detect the remaining 30 compounds following 1 extraction and using
      only 2 mL of urine was developed. The process is inexpensive and uses equipment
      available in most forensic toxicology laboratories. This method is recommended
      for any laboratory that commonly receives specimens collected from sexual assault
      victims and is interested in a more thorough analysis.

PMID- 15516287
TI  - A general screening and confirmation approach to the analysis of designer
      tryptamines and phenethylamines in blood and urine using GC-EI-MS and HPLC
      electrospray-MS.
AB  - Recent additions of designer tryptamines and phenethylamines to the Drug
      Enforcement Administration's schedule of controlled substances necessitate
      analytical procedures for their detection and quantitation. As specific
      immunoassays are not currently available and cross-reactivities with existing
      assays are unknown, a screening method based on gas chromatography-mass
      spectrometry was developed. The method was capable of measuring the
      pentafluoropropionic derivatives of a-methyltryptamine (AMT), N,N
      dimethyltryptamine (DMT), 4-bromo-2,5-dimethoxy-beta-phenethylamine (2CB), N,N
      dipropyltryptamine (DPT), 2,5-dimethyl-4-N-propylthio-beta-phenethylamine (2C-T
      7), and 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DiPT). Separation was
      optimized to allow tentative identification of metabolites, which display common
      electron impact ionization fragmentation patterns. The screening method gave
      limits of detection between 5 and 10 ng/mL and demonstrated linearity between 50
      and 1000 ng/mL. The method was successfully applied to blood and urine samples in
      suspected AMT intoxications. Confirmation of 5-MeO-DiPT in one of the subjects'
      urine was achieved using liquid chromatography-mass spectrometry (LC-MS).
      Quantitation by selected ion monitoring (SIM) yielded a urinary concentration of
      229 ng/mL. The method was linear from 25 to 1500 ng/mL with a correlation
      coefficient of 0.995. The limit of detection was 5 ng/mL in urine on the LC-MS.
      Two additional peaks were observed and presumed to be metabolic products reported
      previously as 5-methoxy-N-isopropyltryptamine (5-MeO-iPT) and 5-methoxy-N,N
      diisopropyltryptamine-N'-oxide (5-MeO-DiPT-N-oxide).

PMID- 15516288
TI  - Deposition characteristics of methamphetamine and amphetamine in fingernail
      clippings and hair sections.
AB  - Fingernail clippings collected from 97 consenting females, who admitted
      amphetamines and/or opiates use and are currently under treatment, were
      quantitatively analyzed for the presence of methamphetamine and amphetamine.
      Sixty-two subjects were found positive for methamphetamine/amphetamine. Paired
      nail-hair specimens were collected from 6 of these subjects for a 12-week period
      and analyzed to determine the duration of detectability and deposition
      characteristics of amphetamines in fingernails; whether data derived from the
      analysis of nail clippings and hair sections are reflective of drug use patterns;
      and whether there is a relationship between the analytical data derived from the
      paired nail-hair specimens. Typical sample pre-treatment procedures and GC-MS
      protocols were evaluated to establish the validity of various analytical
      parameters and to ensure that the resulting data can be properly interpreted.
      Major findings include 1. Methamphetamine was found in the nails of 62 subjects
      collected in Week 0. The distribution of methamphetamine concentrations (ng/mg)
      in these nail samples are range, 0.46-61.50; mean, 9.96; and standard deviation:
      13.33. The corresponding data for amphetamine are < 0.20-5.42, 0.93, and 1.01,
      respectively. 2. Sectional analyses of hair samples collected from 6 subjects in
      Week 0 show methamphetamine concentrations peak at different distances from the
      root. 3. The concentrations of methamphetamine and amphetamine in nail clippings
      are generally lower than the first 1.5-cm section of hair samples collected at
      the same time from the same individual. 4. Amphetamine/ methamphetamine
      concentration ratios in nail clippings and hair samples are comparable. 5.
      Methamphetamine concentration in the nail clippings collected at Weeks 0, 4, 8,
      and 12 decreases in a pattern similar to that exhibited by the first 1.5-cm
      sections of the hair samples collected at the same time.

PMID- 15516289
TI  - Sevoflurane analysis in serum by headspace gas chromatography with application to
      various biological matrices.
AB  - Sevoflurane is a nonflammable general anesthetic administered by inhalation of
      vaporized liquid that rapidly partitions out of aqueous biological matrices into
      a gaseous phase because of its volatility and hydrophobicity. We describe a
      headspace analysis of sevoflurane that can be performed without the use of an
      expensive automated headspace analyzer. Sevoflurane standards (0-109 mg/L) and
      quality control specimens (12.2 and 72.9 mg/L) were prepared and quantitated on
      an intraday and interday basis. Headspace gas was manually injected (150 degrees
      C) with a 2.5-mL gas-tight syringe into a Perkin-Elmer model 8500 gas
      chromatograph equipped with a 6-ft x 2-mm i.d. glass column (100 degrees C)
      containing 0.2% Carbowax 1500 on Carbopak C packing with a flame-ionization
      detector (200 degrees C), which allowed for elution of the internal standard, 1
      propanol (1.56 min), and sevoflurane (2.92 min). Linear regression of the peak
      area ratios of sevoflurane to 1-propanol (6.38 g/L), versus the sevoflurane
      concentrations yielded an average intraday correlation coefficient of 0.989 (S.D.
      = 0.003, n = 5) and mean quality control specimen values of 14.19 mg/L (C.V. =
      5.1%, n = 5) and 66.72 mg/L (C.V. = 3.3%, n = 5). The average interday standard
      curve correlation coefficient was 0.987 (S.D. = 0.01, n = 5), and the mean
      quality control specimen values were 12.22 mg/L (C.V. = 13.7%, n = 5) and 74.27
      mg/L (C.V. = 8.7%, n = 5). The chromatographic method described produced accurate
      and reproducible results with a simple on-column headspace gas injection. This
      method allows for quantitation of sevoflurane in various biological matrices by
      chromatographic separation of the headspace gas in a sealed specimen container.

PMID- 15516290
TI  - Urine concentrations of fentanyl and norfentanyl during application of Duragesic
      transdermal patches.
AB  - A study of the urinary concentration of fentanyl (F) and its major metabolite
      norfentanyl (NF) in chronic pain patients treated with the Duragesic continuous
      release transdermal patches is presented. These patches are available in 10, 20,
      30, and 40 cm(2) sizes releasing 25, 50, 75, and 100 microg/h F, respectively. F
      is rapidly and extensively metabolized, with NF as the major metabolite. Five
      hundred-forty six random urine specimens were collected from chronic pain
      patients wearing 25, 50, 75, or 100 ug F transdermal patches. Urine specimens
      were collected from hours after application to several days later after
      continuous F release. Each specimen was analyzed for F, NF, creatinine, and pH.
      Additionally, each was screened by enzyme immunoassay for the following:
      amphetamines, barbiturates, benzodiazepines, cocaine metabolite, methadone,
      phencyclidine, d-propoxyphene, opiates, and marijuana metabolites. All positive
      screening results were confirmed by gas chromatography-mass spectrometry (GC-MS).
      F and NF were isolated from urine by solid-phase extraction then identified and
      quantified by GC-MS in SIM mode. The LODs and LOQs for F and NF were 3 ng/mL,
      respectively. The results of F and NF analysis of urine form those wearing 25
      microg patches (N = 142) was mean F, 47 ng/mL with a range of 0 to 983 ng/mL, and
      97% of the specimens contained < 200 ng/mL and mean NF, 175 ng/mL with a range of
      0-980 ng/mL, while 95% of the specimens contained < 400 ng/mL. The results of F
      and NF analysis of urine form those wearing 50 microg patches (N = 184) was: mean
      F, 74 ng/mL with a range of 0 to 589 ng/mL, and 92% of the specimens contained <
      200 ng/mL and mean NF, 257 ng/mL with a range of 0-2200 ng/mL, and 98% of the
      specimens contained < 1000 ng/mL. The results of F and NF analysis of urine form
      those wearing 75 microg patches (N = 85) was mean F, 107 ng/mL with a range of 0
      to 1280 ng/mL, and 98% of the specimens contained < 400 ng/mL and mean NF, 328
      ng/mL with a range of 0-5630 ng/mL, and 99% of the specimens contained < 1000
      ng/mL. The results of F and NF analysis of urine form those wearing 100 ug
      patches (N = 135) was mean F, 100 ng/mL with a range of 0 to 1080 ng/mL, while
      96% of the specimens contained < 400 ng/mL and mean NF, 373 ng/mL with a range of
      0-5730 ng/mL, and 95% of the specimens contained < 1000 ng/mL. The incidence of
      other drugs detected as a percentage the specimens was opiates, 48%,
      benzodiazepines, 43%; barbiturates, 3%; methadone, 4%; marijuana metabolite, 3%;
      and cocaine metabolite, 1%. With the exception of F and/or NF, no other drugs
      were detected in 25% of the specimens. These data demonstrate the wide variation
      in concentrations of F and NF in random urine specimens following application of
      Duragesic patches. However, these values obtained during therapeutic use far
      exceed concentrations previously reported in fatal poisoning. In general, one may
      expect to find urine NF concentrations 3-4 times higher than those of F.

PMID- 15516291
TI  - Urinary analysis of four testosterone metabolites and pregnanediol by gas
      chromatography-combustion-isotope ratio mass spectrometry after oral
      administrations of testosterone.
AB  - The most frequently used method to demonstrate testosterone abuse is the
      determination of the testosterone and epitestosterone concentration ratio (T/E
      ratio) in urine. Nevertheless, it is known that factors other than testosterone
      administration may increase the T/E ratio. In the last years, the determination
      of the carbon isotope ratio has proven to be the most promising method to help
      discriminate between naturally elevated T/E ratios and those reflecting T use. In
      this paper, an excretion study following oral administration of 40 mg
      testosterone undecanoate initially and 13 h later is presented. Four testosterone
      metabolites (androsterone, etiocholanolone, 5 alpha-androstanediol, and 5 beta
      androstanediol) together with an endogenous reference (5 beta-pregnanediol) were
      extracted from the urines and the delta(13)C/(12)C ratio of each compound was
      analyzed by gas chromatography-combustion-isotope ratio mass spectrometry. The
      results show similar maximum delta(13)C-value variations (parts per thousand
      difference of delta(13)C/(12)C ratio from the isotope ratio standard) for the T
      metabolites and concomitant changes of the T/E ratios after administration of the
      first and the second dose of T. Whereas the T/E ratios as well as the
      androsterone, etiocholanolone and 5 alpha-androstanediol delta(13)C-values
      returned to the baseline 15 h after the second T administration, a decrease of
      the 5 beta-androstanediol delta-values could be detected for over 40 h. This
      suggests that measurements of 5 beta-androstanediol delta-values allow the
      detection of a testosterone ingestion over a longer post-administration period
      than other T metabolites delta(13)C-values or than the usual T/E ratio approach.

PMID- 15516292
TI  - Metabolic profile of famprofazone following multidose administration.
AB  - One of the 14 different drugs known to be metabolized to methamphetamine and/or
      amphetamine is famprofazone, a component in the multi-ingredient formulation
      Gewodin. Because of its conversion to methamphetamine and amphetamine, which can
      result in positive drug-testing results, the excretion pattern of these
      metabolites is critical for proper interpretation of drug-testing results.
      Multiple doses of famprofazone were administered to healthy volunteers with no
      previous history of methamphetamine, amphetamine, or famprofazone use. Following
      administration, urine samples were collected ad lib for nine days, and pH,
      specific gravity, and creatinine values were determined. To determine the
      methamphetamine and amphetamine excretion profile, samples were extracted,
      derivatized, and analyzed by gas chromatography-mass spectrometry (GC-MS). Peak
      concentrations of methamphetamine ranged from 5327 to 14,155 ng/mL and from 833
      to 3555 ng/mL for amphetamine and were reached between 12:22 and 48:45 h post
      initial dose. There were 15-19 samples per subject that were positive under HHS
      testing guidelines, with the earliest at 03:37 h post initial dose and as late as
      70:30 h post last dose. Methamphetamine and amphetamine were last detected (LOD >
      or = 5 ng/mL) up to 159 h and 153 h post last dose for methamphetamine and
      amphetamine, respectively. GC-MS was also used to determine the enantiomeric
      composition of methamphetamine and amphetamine. This analysis revealed both
      enantiomers were present in a predictable pattern.

PMID- 15516293
TI  - Cannabis (marijuana) contamination of United States and foreign paper currency.
AB  - It is well known that United States paper currency in general circulation is
      contaminated with trace amounts of illicit substances such as cocaine, heroin and
      marijuana. As is the case with cocaine, differentiating "background levels" of
      the various cannabinoid constituents of Cannabis sativa L., namely, Delta(9)
      tetrahydrocannabinol (THC), cannabinol (CBN), and cannabidiol (CBD) contaminating
      currency found in the general circulation from currency associated with illegal
      drug activity is imperative if a legal nexus is to be established with the
      latter. We analyzed 165 randomly collected paper currency notes from 12 U.S.
      cities (N = 125) and 4 foreign countries (N = 40) for THC, CBD, CBN, 11-nor-9
      carboxy-Delta(9)-tetrahydrocannabinol, and 11-hydroxy-Delta(9)
      tetrahydrocannabinol. Uncirculated US 1 dollar notes were added as negative
      controls. Drug residues were washed from individual bills, extracted using a
      liquid-liquid extraction protocol, derivatized, and quantitated by gas
      chromatography-mass spectrometry by selected ion monitoring. For the US 1 dollar
      currency, THC was present in 1.6% (2 notes), CBN 10.31% (13 notes), CBD 1.6% (2
      notes). The following concentrations were determined: 0.085 microg/bill and 0.146
      microg/bill for THC; 0.014-0.774 microg/bill (mean 0.166 microg/bill) for CBN;
      and 0.032 microg/bill and 0.086 microg/bill for CBD. For the foreign currency
      (Colombia, Qatar, India, and New Zealand), THC and CBN were present in 22.5% (9
      notes). The following concentration ranges were determined: THC 0.026-0.065
      microg/bill (mean 0.049 microg/bill), CBN 0.061-0.197 microg/bill (mean 0.115
      microg/bill). All of the positive THC and CBN were found in the New Zealand
      polypropylene notes. This study demonstrated that marijuana (cannabinoids) may
      contaminate both paper and plastic currency.

PMID- 15516294
TI  - A liquid chromatographic-electrospray-tandem mass spectrometric method for
      quantitation of quetiapine in human plasma and liver microsomes: application to
      study in vitro metabolism.
AB  - Quetiapine is an atypical antipsychotic agent for the treatment of schizophrenia.
      After an oral dose it is absorbed rapidly and extensively metabolized in the
      liver, resulting in low plasma concentrations of the parent drug. A sensitive
      analytical method is needed. A liquid chromatographic-electrospray-tandem mass
      spectrometric (LC-ESI-MS-MS) method combined with a simple liquid-liquid
      extraction has been developed for the measurement of quetiapine in human plasma
      and in human liver microsomes (HLM). Clozapine is used as internal standard.
      Plasma samples or microsomes quenched with methanol (100 microL) were made basic
      and extracted with 3 mL n-butyl chloride. The reconstituted extracts were
      analyzed by LC-ESI-MS-MS. Selective reaction monitoring of MH(+) at m/z 384 and
      327 resulted in strong fragment ions at m/z 253 and 192 for quetiapine and
      clozapine, respectively. Recovery of quetiapine and clozapine ranged from 62 to
      73%. Intrarun accuracy and precision determined at 1.0 (lower limit of
      quantitation), 2.5, 200, and 400 ng/mL did not exceed 7% deviation from target
      and the %CV did not exceed 5.5%. The % target +/- %CV for interrun accuracy and
      precision were at least 95% +/- 7.4% at concentrations of 2.5, 200, and 400
      ng/mL. Plasma samples (2.5 and 400 ng/mL) stored at room temperature for 24 h or
      after 3 cycles of freeze/thaw were all stable (maximum % deviation < or = 11.0%).
      Processed extracts (2.5 and 400 ng/mL) stored for 7 days at -20 degrees C or 6
      days on the autosampler were all stable (maximum % deviation < or = 11.5%). The
      method has been used to study quetiapine utilization during incubation with HLM
      or with cDNA-expressed human cytochrom P450s (CYP). Quetiapine is extensively
      metabolized by CYP 3A4 and CYP 2D6 and to a lesser extent by CYP 3A7, CYP 3A5,
      and CYP 2C19.

PMID- 15516295
TI  - Enantiomeric separation and quantitation of (+/-)-amphetamine, (+/-)
      methamphetamine, (+/-)-MDA, (+/-)-MDMA, and (+/-)-MDEA in urine specimens by GC
      EI-MS after derivatization with (R)-(-)- or (S)-(+)-alpha-methoxy-alpha
      (trifluoromethy)phenylacetyl chloride (MTPA).
AB  - In drug testing, the presence of methamphetamine in urine is generally confirmed
      by a gas chromatography-mass spectrometry (GC-MS) method. Derivatization of the
      compound to a perfluoroalkylamide, prior to confirmation, typically yields better
      chromatographic separation. Once methamphetamine is detected, a second GC-MS test
      is necessary to distinguish positive results from the use of over-the-counter
      medication, Vicks inhaler, or from use of a prescription drug, selegiline
      (Deprenyl). R-(-)-Methamphetamine is the urinary product from legitimate use of
      these medications. The second GC-MS test is to confirm illicit use of (S)-(+)
      methamphetamine. In the procedure, the two methamphetamine isomers are changed to
      the chromatographically separable diastereomers by a chiral derivatizing agent,
      (S)-(-)-trifluoroacetylprolyl chloride (TPC). But the method has inherent
      limitations. Racemization of the reagent produces mixed diastereomers even from
      pure (S)-(+)-methamphetamine. Instead of using TPC, we utilized (R)-(-)-alpha
      methoxy-alpha-(trifluoromethyl)phenylacetyl chloride (MTPA) to prepare the amides
      of diastereomers of methamphetamine. No racemization was observed with this
      reagent. The method was extended to resolve GC peaks of (R)-(-)- and (S)-(+)
      isomers of amphetamine, 3,4-methylenedioxyamphetamine (MDA), N-methyl-MDA (MDMA),
      and N-ethyl-MDA (MDEA). Three ions from the drug and two ions from the deuterated
      internal standard were monitored to characterize and quantitate the drugs. For
      MDEA, only one ion was used. The quantitation was linear over 25 to 5000 ng/mL
      for MDEA and 25 to 10,000 ng/mL for all other drugs. Correlation coefficients
      were > 0.996. Precision calculated as the coefficient of variation at the
      calibrator concentration of 500 ng/mL was within +/- 11% for all drugs. The
      method was applied to test 43 urine specimens. In 91% of the methamphetamine
      positive specimens, only the (S)-(+)-isomer was detected. In all MDMA-positive
      specimens, the concentrations of (R)-(-)-isomer were greater than the (S)-(+)
      isomer indicating longer retention of (R)-(-)-isomer in the human body. The
      specimen concentrations (R + S) compared well with that of a non-chiral method
      that used 4-carboethoxyhexafluorobutyryl chloride as derivatizing agent. But the
      MTPA method has some advantage. It alone can replace the two GC-MS methods needed
      to confirm the presence of (S)-(+)-isomers of amphetamine and methamphetamine.

PMID- 15516296
TI  - An uncertainty budget for the measurement of ethanol in blood by headspace gas
      chromatography.
AB  - An uncertainty budget was constructed for the measurement of ethanol in blood by
      headspace gas chromatography. The uncertainty budget, covering the analytical
      range of ethanol concentrations up to 3.00 g/kg, included analytical uncertainty
      components, traceability uncertainty components, and effects caused by
      interindividual variation in blood water content. The analytical combined
      standard uncertainty was estimated from duplicate measurements of real samples
      and included contributions from headspace recovery, variation between columns,
      injection, repeatability of analytical signals, and statistical uncertainty of
      the calibration function. The traceability uncertainty was estimated in a sub
      budget based on information about the calibrator and about the preparation of the
      aqueous standards. Two uncertainty components depended on the interindividual
      variation in blood water content. First, it caused uncertainty on the density of
      the blood, and second, it had an effect on the gas phase concentration of ethanol
      when doing the headspace sampling. These effects as well as their covariance were
      included in the uncertainty budget. For fresh blood samples, the analytical
      uncertainty was the dominating uncertainty component, accounting for
      approximately 90% of the variance. For blood samples collected 100 h postmortem,
      the interindividual variation in blood water content was the largest uncertainty
      component. It was demonstrated that subtracting a "safety margin" of 0.1 g/kg
      from the results was sufficient to keep the risk of committing a type 1 error
      below 0.1% in ethanol concentrations ranging up to 2 g/kg for fresh blood
      samples. This risk was higher for postmortem blood samples because of the higher
      uncertainty of measurement, but still less than approximately 1.4%.

PMID- 15516297
TI  - A fatal overdose of cocaine associated with coingestion of marijuana,
      buprenorphine, and fluoxetine. Body fluid and tissue distribution of cocaine and
      its metabolites determined by hydrophilic interaction chromatography-mass
      spectrometry(HILIC-MS).
AB  - Chromatographic separation of highly polar basic drugs with ideal ionspray mass
      spectrometry volatile mobile phases is a difficult challenge. A new
      quantification procedure was developed using hydrophilic interaction
      chromatography-mass spectrometry with turbo-ionspray ionization in the positive
      mode. After addition of deuterated internal standards and simple clean-up liquid
      extraction, the dried extracts were reconstituted in 500 microL pure acetonitrile
      and 5 microL was directly injected onto a Waters Atlantis HILIC 150- x 2.1-mm, 3
      microm column. Chromatographic separations of cocaine, seven metabolites, and
      anhydroecgonine were obtained by linear gradient-elution with decreasing high
      concentrations of acetonitrile (80-56% in 18 min). This high proportion of
      organic solvent makes it easier to be coupled with MS. The eluent was buffered
      with 2 mM ammonium acetate at pH 4.5. Except for m-hydroxy-benzoylecgonine, the
      within-day and between-day precisions at 20, 100, and 500 ng/mL were below 7 and
      19.1%, respectively. Accuracy was also below +/- 13.5% at all tested
      concentrations. The limit of quantification was 5 ng/mL (%Diff < 16.1, %RSD <
      4.3) and the limit of detection below 0.5 ng/mL. This method was successfully
      applied to a fatal overdose. In Switzerland, cocaine abuse has dramatically
      increased in the last few years. A 45-year-old man, a known HIV-positive drug
      user, was found dead at home. According to relatives, cocaine was self-injected
      about 10 times during the evening before death. A low amount of cocaine (0.45 mg)
      was detected in the bloody fluid taken from a syringe discovered near the corpse.
      Besides injection marks, no significant lesions were detected during the forensic
      autopsy. Toxicological investigations showed high cocaine concentrations in all
      body fluids and tissues. The peripheral blood concentrations of cocaine,
      benzoylecgonine, and methylecgonine were 5.0, 10.4, and 4.1 mg/L, respectively.
      The brain concentrations of cocaine, benzoylecgonine, and methylecgonine were
      21.2, 3.8, and 3.3 mg/kg, respectively. The highest concentrations of norcocaine
      (about 1 mg/L) were measured in bile and urine. Very high levels of cocaine were
      determined in hair (160 ng/mg), indicating chronic cocaine use. A low
      concentration of anhydroecgonine methylester was also found in urine (0.65 mg/L)
      suggesting recent cocaine inhalation. Therapeutic blood concentrations of
      fluoxetine (0.15 mg/L) and buprenorphine (0.1 microg/L) were also discovered. A
      relatively high concentration of Delta(9)-THC was measured both in peripheral
      blood (8.2 microg/L) and brain cortex (13.5 microg/kg), suggesting that the
      victim was under the influence of cannabis at the time of death. In addition,
      fluoxetine might have enhanced the toxic effects of cocaine because of its weak
      pro-arrhythmogenic properties. Likewise, combination of cannabinoids and cocaine
      might have increase detrimental cardiovascular effects. Altogether, these results
      indicate a lethal cocaine overdose with a minor contribution of fluoxetine and
      cannabinoids.

PMID- 15516298
TI  - Lorazepam and driving impairment.
AB  - Lorazepam (Ativan), is a benzodiazepine frequently used to manage anxiety,
      presurgically, and as a sedative. Common side effects include sedation,
      dizziness, weakness, unsteadiness, and disorientation. Consequently, lorazepam
      can have a significant effect on driving ability. We reviewed all positive
      lorazepam drug-impaired driving cases submitted to the Washington State
      Toxicology Laboratory between January 1998 and December 2003. The mean
      concentration found in the blood of these drivers (n = 170) was 0.048 mg/L (std.
      dev. = 0.06, median = 0.03). Concentrations ranged from < 0.005 to 0.39 mg/L.
      Eighty-six percent of these drivers tested positive for other drugs in addition
      to lorazepam that may have contributed to their impairment. There were 23 cases
      in which lorazepam was the only drug detected. The mean concentration found in
      the blood of these drivers was 0.051 mg/L (median = 0.03, range < 0.01-0.38).
      This population was 56% male, with a mean age of 39.5 years, (range 16-72). We
      obtained Drug Recognition Expert reports containing details of events surrounding
      arrest and performance on field sobriety tests for 10 of the remaining cases in
      which no drugs other than lorazepam were present. Lorazepam concentrations in
      these cases averaged 0.050 mg/L (median = 0.04, range 0.01-0.13 mg/L). This
      review of these subjects indicates that lorazepam is capable of causing
      significant impairment to driving and psychomotor abilities, independent of the
      concentration detected.

PMID- 15516299
TI  - Suspected GHB overdoses in the emergency department.
AB  - Blood specimens from 146 suspected gamma-hydroxybutyrate (GHB) overdose cases,
      presenting to an emergency department in Washington State over a 12-month period,
      were analyzed for GHB and other drugs. Of these 146 patients, GHB was confirmed
      in approximately one-third of the patients (N = 54), sometimes in potentially
      toxic concentrations. These patients were aged between 17 and 59 years (median 28
      years), and 83% were male. Blood GHB concentrations ranged from 29 to 490 mg/L
      (mean 137 mg/L; median 103 mg/L). In 36 (67%) of the 54 patients, other drugs
      were additionally detected. Ethanol was measured in 22 (41%) patients, with
      concentrations ranging from 0.01 to 0.26 g/100 mL (median 0.04 g/100 mL). Other
      commonly co-administered drugs included 3,4-methylenedioxymethamphetamine,
      marijuana, methamphetamine, cocaine, and citalopram. Frequently observed clinical
      symptoms on admission for the GHB overdose group included copious vomiting,
      ataxia, lack of gag reflex, respiratory depression, mild acute respiratory
      acidosis, unconsciousness, and sudden altered states of consciousness. Many
      patients required intubation, and several became combative and required
      restraints. The majority of patients were discharged within 6 h of hospital
      admission. However, despite presenting with similar clinical symptoms on
      admission, GHB was not confirmed in 92 of the 146 overdose patients, suggesting
      that GHB overdose cases may frequently be indistinguishable from other drug
      overdoses or medical conditions.

PMID- 15516300
TI  - Evaluation of the Triage PPY on-site testing device for the detection of
      dextropropoxyphene in urine.
AB  - A new point-of-care colloidal metal immunoassay urine drugs-of-abuse testing
      device, the BIOSITE TRIAGE Plus Propoxyphene (TPP), was evaluated for the rapid
      detection of dextropropoxyphene (PPY) and/or its primary metabolite,
      norpropoxyphene (NP), in urine at a total PPY/NP concentration of 300 ng/mL or
      greater. This assay has been added to the Triage device that tests for commonly
      abused drugs. Adding to drug-free urine PPY and NP established the linearity of
      the TPP assay at concentrations of 40%, 80%, 120%, and 160% of the cut-off
      concentration. No significant cross-reactivity was found at 1.0 g/L for 32 drugs
      commonly encountered in emergency department admissions. Significant cross
      reactivity was observed only with diphenhydramine and tricyclic antidepressants.
      TPP results from 160 urine specimens screened for PPY and/or NP were compared to
      those obtained by testing with DRI enzyme immunoassay, Emit II plus immunoassay,
      Abuscreen Online immunoassay and gas chromatography-mass spectrometry (GC-MS).
      There was a 98.8% agreement of positive or negative results between TPP and both
      the DRI and OnLine assays. The two discordant TPP results were due to
      concentrations of NP below the TPP minimum cross-reactivity value of 400 ng/mL.
      These two specimens yielded GC-MS NP concentrations of 262 and 359 ng/mL. These
      NP concentrations were within +/- 20% of the cross-reactivity cut-off value for
      NP for TPP, DRI, and Online. There was only an 88% agreement of positive or
      negative results between TPP and the Emit assay. Twenty urine specimens yielding
      PPY positive results when tested by TPP were negative by Emit testing. The
      discordant TPP results were due to poor cross-reactivity of Emit to NP. A 98.8%
      agreement of positive PPY results was observed between TPP and GC-MS. Discordant
      urines were found to contain PPY concentrations below the cut-off value of the
      assay. TPP was found to be an accurate device for the detection of PPY and NP in
      urine.

PMID- 15516302
TI  - A high-performance liquid chromatographic-atmospheric pressure chemical
      ionization-tandem mass spectrometric method for determination of risperidone and
      9-hydroxyrisperidone in human plasma.
AB  - Risperidone, a benzisoxazole derivative, is an antipsychotic agent used for the
      treatment of schizophrenia. We developed a liquid chromatographic-atmospheric
      pressure chemical ionization-tandem mass spectrometric (LC-APCI-MS-MS) method
      with improved sensitivity, selectivity, and dynamic range for determination of
      risperidone and 9-hydroxyrisperidone in human plasma. A structural analogue of
      risperidone, RO68808 (5 ng/mL), is added as the internal standard to 1 mL of
      human plasma. Plasma is made basic, extracted with pentane/methylene chloride
      (3:1), the organic phase evaporated to dryness, and the residue is reconstituted
      in water with 0.1% formic acid/acetonitrile (20:1). For LC-MS-MS analysis, a
      Metachem Inertsel HPLC column (2.1 x 150 mm, 5-microm particle size) is connected
      to a Finnigan TSQ7000 tandem MS via the Finnigan API interface. Both electrospray
      (ESI) and APCI produced predominantly MH(+) ions for the two analytes and the
      internal standard. Ions detected by selected reaction monitoring correspond to
      the following transitions: m/z 411 to 191 for risperidone, m/z 427 to 207 for 9
      hydroxyrisperidone, and m/z 421 to 201 for the internal standard. APCI provided a
      larger dynamic range (0.1 to 25 ng/mL) and better precision and accuracy than
      ESI. Intrarun accuracy and precision determined at 0.1, 0.25, 2.5, and 15 ng/mL
      were within 12% of target with %CVs not exceeding 10.9%. Interrun accuracy and
      precision determined at the same concentrations were within 9.6% of target with
      %CVs not exceeding 6.7%. Analytes were stable in plasma after 24 h at room
      temperature, 2 freeze-thaw cycles, and 490 days at -20 degrees C.

PMID- 15516301
TI  - Comparison of the Microgenics CEDIA heroin metabolite (6-AM) and the Roche
      Abuscreen ONLINE opiate immunoassays for the detection of heroin use in forensic
      urine samples.
AB  - Current Department of Defense (DoD) and Department of Health and Human Services
      (HHS) procedures for the detection of heroin abuse by testing urine utilize an
      initial opiate (codeine/morphine) immunoassay (IA) screen followed by gas
      chromatography-mass spectrometry (GC-MS) confirmation of 6-acetylmorphine (6-AM),
      if the morphine concentration is above established cutoff. An alternative to the
      current opiates screen for heroin abuse is the direct IA for the metabolite of
      heroin, 6-acetylmorphine. In this regard, the performance of the Microgenics
      CEDIA heroin metabolite (6-AM) screening reagent was assessed. This evaluation
      was conducted on the P module of a Hitachi Modular automated IA analyzer
      calibrated using 6-AM at 10 ng/mL. Reproducibility, linearity, accuracy,
      sensitivity, and interferences associated with use of the 6-AM IA reagent were
      evaluated. The IA reagent precision (percent coefficient of variation (%CV))
      around each of seven standards was less than 0.63%, with a linearity (r(2)) value
      of 0.9951. A total of 37,713 active duty service members' urine samples were
      analyzed simultaneously using the CEDIA heroin metabolite (6-AM) reagent and the
      Roche Abuscreen ONLINE opiate reagent to evaluate both the prevalence rate of 6
      AM in the demographic group and the sensitivity and specificity of the reagents
      for the detection of heroin use. Of the 37,713 samples tested using the CEDIA
      heroin metabolite (6-AM) reagent, three samples screened positive at the DoD and
      HHS cutoff of 10 ng/mL. One of the three samples confirmed positive for 6-AM by
      GC-MS above the cutoff of 10 ng/mL, the two remaining samples confirmed negative
      for 6-AM at a GC-MS limit of detection (LOD) of 2.1 ng/mL. In contrast, the Roche
      Abuscreen ONLINE opiate IA produced 74 opiate-positive results for
      codeine/morphine, with 6 of the 74 specimens confirming positive for morphine
      above the DoD cutoff concentration of 4000 ng/mL (8% DoD morphine confirmation
      rate), only one of the 74 opiate-positive screen specimens confirmed positive for
      6-AM above the 10 ng/mL GC-MS cutoff concentration. As a further check of the
      sensitivity and specificity of the Microgenics 6-AM IA reagent, human urine
      samples (n = 87) known to contain 6-AM by GC-MS, were re-analyzed using both IA
      reagents. All 87 of the samples screened positive using the CEDIA heroin
      metabolite (6-AM) assay. However, using the Roche ONLINE opiate reagent, 12 of
      the known 6-AM positives screened negative at the DoD and HHS screening cutoff of
      2000 ng/mL (morphine). Of the remaining 75 samples that screened positive by the
      ONLINE opiate reagent, five of the samples did not contain morphine above the DoD
      GC-MS cutoff concentration of 4000 ng/mL and would not have required 6-AM
      analysis. However, under the HHS GC-MS morphine cutoff concentration of 2000
      ng/mL all 75 samples would have required 6-AM analysis. Furthermore, using the
      current DoD opiate screen, 17 out of 87 samples known to contain 6-AM would have
      gone undetected (19.5% false-negative rate); additionally, even under the more
      stringent HHS opiate screening standards 12 out of the 87 samples known to
      contain 6-AM would also have gone undetected (13.8% false-negative rate). The
      Microgenics CEDIA heroin metabolite (6-AM) reagent assay appears well adapted for
      the rapid and specific detection of heroin abuse as an alternative for, or an
      adjunct test to, the current opiates (codeine/morphine) IA screening procedure.

PMID- 15516303
TI  - Validation of the Cozart microplate EIA for cocaine and metabolites in oral
      fluid.
AB  - The purpose of these studies was to determine the performance characteristics of
      the Cozart microplate EIA for the detection of cocaine and cocaine metabolites in
      oral fluid. A total of 217 samples were collected using the Cozart RapiScan oral
      fluid Collection System from donors who were receiving treatment and being
      monitored for their addiction. The samples were screened in the laboratory using
      the Cozart microplate EIA for cocaine and metabolites and confirmed using gas
      chromatography-mass spectrometry (GC-MS). The samples were stored frozen until
      analysis by GC-MS. Of the 217 samples tested, 116 were positive for cocaine
      and/or cocaine metabolites. The Cozart microplate EIA for cocaine, using a cutoff
      of 30 ng/mL benzoylecgonine equivalents in neat oral fluid, had a sensitivity of
      95.7% +/- 2.0% and specificity of 100% +/- 0.7%. A series of potential
      adulterants of oral fluid were evaluated and shown not to alter the outcome of
      the test result.

PMID- 15516304
TI  - Two cases involving clomipramine intoxication.
AB  - Clomipramine and its active metabolite norclomipramine were identified and
      quantitated in multiple tissues recovered from two postmortem cases using liquid
      chromatography-mass spectrometry. In both cases clomipramine toxicity was
      assessed primarily upon levels determined from brain samples. This communication
      supplements the database on clomipramine and norclomipramine by providing
      quantitative determinations of both parent drug and metabolite in multiple
      tissues. A literature search revealed a paucity of data on clomipramine and
      norclomipramine levels in general and a total absence of documented brain levels.
      In patients who have undergone long-term tricyclic antidepressant (TCA) therapy,
      blood and liver analysis alone may not be sufficient to establish toxicity. Such
      patients can sequester substantial amounts in liver, a concern because the TCAs
      are subject to significant postmortem redistribution. When conducting postmortem
      investigations, the inclusion of brain determination provides valuable
      information in assessing the magnitude of toxicity in cases involving
      clomipramine and its active metabolite norclomipramine.

PMID- 15516305
TI  - Hydroxycarbazepine distribution in three postmortem cases.
AB  - This paper presents three cases investigated by the Office of the Chief Medical
      Examiner where hydroxycarbazepine, the active metabolite of the anticonvulsant
      prodrug oxcarbazepine, was detected in the biological specimens submitted for
      toxicological analysis. Hydroxycarbazepine was quantitated using a single-step pH
      5 extraction and detection on a DB-5 column by gas chromatography-nitrogen
      phosphorus detection. In the three cases, the heart blood concentrations were
      34.6, 40.5, and 3.7 mg/L, respectively. In cases 2 and 3, the peripheral blood
      concentrations were 36 and 4.1 mg/L, respectively. In each case, the medical
      examiner ruled that the hydroxycarbazepine was an incidental finding to the cause
      of death.

PMID- 15516306
TI  - Addicted to driving under the influence--a GHB/GBL case report.
AB  - A 38-year-old male was arrested 7 times over an 8-month period for driving under
      the influence (DUI) of drugs. In each incident, gamma-hydroxybutyrate (GHB) was
      determined to be the causative agent. A blood specimen was drawn between 1.5 and
      2.5 h after first police contact in each arrest. GHB was analyzed by gas
      chromatography-mass spectrometry, following extraction from blood using ethyl
      acetate and subsequent derivatization using BSTFA/TMCS. Blood GHB concentrations
      ranged from 44 to 184 mg/L (N = 7, mean 100 mg/L, median 73 mg/L). Overall signs
      of impairment included erratic driving (severe lane travel, collisions, and near
      collisions), slurred speech, disorientation, slow to react, shaking, agitation,
      unable to focus, poor coordination and balance, poor performance in field
      sobriety tests, somnolence, and unconsciousness. On only one occasion were other
      drugs present in the subject's blood (thiopental and diazepam), which may have
      contributed to the observed driving impairment. During several police interviews,
      the subject stated he was addicted to GHB and gamma-butyrolactone (GBL), and
      admitted to previously taking "RenewTrient", "Dream On", "V35", "fitness
      supplements", and/or "GBL". During the same period as his DUI arrests, the
      subject had been admitted at least six times to different hospitals for GHB/GBL
      intoxications.

PMID- 15516307
TI  - Hair to document drug-facilitated crimes: four cases involving bromazepam.
AB  - The use of a drug to modify a person's behavior for criminal gain is not a recent
      phenomenon. However, the recent increase in reports of drug-facilitated crimes
      (sexual assault, so-called DFSA, robbery) has caused alarm in the general public.
      Drugs used can be difficult to detect (active products at low dosages, chemical
      instability), possess amnesic properties, and can be quickly cleared from body
      fluids. In case of long delay between the alleged crime and clinical examination,
      collection of blood or even urine can be of little value. This is the reason why
      this laboratory developed an original approach based on hair testing by liquid
      chromatography-tandem mass spectrometry. To explore the detectability of a single
      absorption of bromazepam in hair, two volunteers (male and female) received a 6
      mg dose. A strand of hair was sampled about one month after exposure and was cut
      into three segments of 2-cm long. After pulverization, 20 mg of hair was
      incubated overnight in a phosphate buffer (pH 8.4). The aqueous phase was
      extracted with 5 mL of a mixture of diethyl ether/methylene chloride (80:20) in
      the presence of diazepam-d5, which was used as internal standard (IS). Hair
      extract was separated on a XTerra MS C18 column using a gradient of acetonitrile
      and formate buffer. Detection was based on two daughter ions: transitions m/z
      316.0 to 182.2 and 209.3 and m/z 290.1 to 154.1 and 198.2 for bromazepam and the
      IS, respectively. In the hair of the two subjects, bromazepam was detected in the
      proximal segment at 0.8 and 4.7 pg/mg, respectively. Hair analysis was applied to
      four authentic criminal cases. In the two first cases, bromazepam tested positive
      in the corresponding hair segment at 5.7, and 10.3 pg/mg. In another case, head
      hair was sampled 19 weeks after the alleged offense, and its length (< 4 cm) did
      not allow analysis of the corresponding period. However, 4.1 pg/mg of bromazepam
      was quantified in the victim's pubic hair. In these three cases, concentrations
      were consistent with a single exposure to bromazepam. In the last case,
      bromazepam was detected at 15 pg/mg in the segment corresponding to the period of
      the alleged offence but also in the range 2 to 7 pg/mg in the four other
      consecutive segments, making a single exposure statement difficult.

PMID- 15516308
TI  - Fatal overdoses associated with quetiapine.
AB  - Quetiapine (Seroquel) is an atypical antipsychotic drug belonging to a new
      chemical class, the benzothiazepine derivatives. We present three cases from the
      Provincial Toxicology Center of British Columbia, Canada in which suicidal
      overdose deaths were associated with quetiapine. The blood specimens were
      initially subjected to a thorough qualitative analysis. Basic drugs were screened
      for by liquid-liquid extraction followed by gas chromatography-nitrogen
      phosphorus (GC-NPD) and gas chromatography-mass spectrometry-electron impact
      detection utilizing both in-house and commercial search libraries. Acidic and
      neutral drugs were screened for by liquid-liquid extraction followed by high
      performance liquid chromatography-diode-array detection. Volatiles were assayed
      by gas chromatography-flame-ionization detection. Quetiapine was assayed in
      biological specimens by basic extraction with n-butyl chloride and derivatized
      with 50 microL of MTBSTFA and separation by GC-NPD. Linearity was observed up to
      2.0 mg/L. Samples with concentrations exceeding the linearity were diluted. These
      cases were chosen for study because they were all deaths as a result of suicidal
      ingestion of drugs in which quetiapine was considered a significant factor. The
      concentrations of quetiapine in these cases are 6-16 times greater than the upper
      reported therapeutic range (0.1-1.0 mg/L). In case #1, the concentrations of
      quetiapine found were 7.20 mg/L (19 micromol/L) in blood and 0.93 mg/L (2.4
      micromol/L) in vitreous fluid. In case #2, the concentrations of quetiapine found
      were 16 mg/L in blood (42 micromol/L), 120 mg/kg (310 micromol/kg) in liver, and
      1.8 mg/L (4.6 micromol/L) in vitreous fluid. In case #3, the concentrations of
      quetiapine found in femoral blood was 5.90 mg/L (15 micromol/L). In all cases,
      drugs in addition to quetiapine were detected, but in cases #1 and #2, the cause
      of death was considered to be a quetiapine overdose and the other drugs were not
      considered to be contributory. Case #3 was considered a mixed drug overdose.

PMID- 15516309
TI  - A non-fatal case of sodium toxicity.
AB  - A non-fatal case of sodium toxicity in a six-year-old boy is presented.
      Hypernatremia is the clinical term for an excessive concentration of sodium
      relative to water in the body. The diagnosis of hypernatremia was made at serum
      sodium (Na(+)) concentrations exceeding 150 mEq/L, and few people have been
      reported to survive concentrations greater than 160 mEq/L. This case involves a
      six-year-old boy who was taken to the hospital following a seizure attack, and
      lab analyses revealed serum sodium (Na(+)) levels of 234 mEq/L and serum chloride
      (Cl(-)) levels of 205 mEq/L. Clinical tests ruled out diabetes insipidus,
      dehydration, renal pathology, and other primary causes of hypernatremia. The
      child's purported history of pica, and the lab results indicating corresponding
      increases in levels of serum sodium (Na(+)) and serum (Cl(-)), led to a diagnosis
      of acute sodium toxicity by ingestion of sodium chloride. A search of the boy's
      house led to the discovery of rock salt in the cabinet and a container of table
      salt. Extrapolating from the serum sodium (Na(+)) level, it was estimated that
      the child had ingested approximately four tablespoons of rock salt, leading to
      the acute toxicity. A literature search revealed that the serum sodium (Na(+))
      concentration in the present report was the highest documented level of sodium in
      a living person.

PMID- 15516310
TI  - Postmortem morphine concentrations following use of a continuous infusion pump.
AB  - We report a case involving unusually high postmortem morphine concentrations in a
      44-year-old male with end-stage pancreatic cancer. He was receiving morphine for
      pain control via a single subclavian intravenous catheter. Allegations of foul
      play were made by family members at the time of death, so a full autopsy was
      performed. Comprehensive toxicology on autopsy samples indicated that morphine
      was the only drug present. Quantitative analysis of free and total morphine
      revealed extraordinarily high concentrations of the drug. Free morphine
      concentrations in heart blood, vitreous fluid, brain, liver, stomach contents,
      and urine were 96 mg/L, 52 mg/L, 26 mg/kg, 88 mg/kg, 82 mg/L, and 976 mg/L,
      respectively. Total morphine concentrations in heart blood, vitreous fluid,
      brain, liver, and stomach contents were 421 mg/L, 238 mg/L, 65 mg/kg, 256 mg/kg,
      and 325 mg/L, respectively. Records indicate that the infusion pump may have
      continued to deliver the drug for 15-45 min following death. Despite compelling
      toxicological data, the cause of death was determined to be complication of
      adenocarcinoma of the pancreas, and the manner was natural. This report
      highlights issues surrounding postmortem toxicological interpretation within the
      context of chronic pain management.

PMID- 15516311
TI  - Tissue distribution of molidone in a multidrug overdose.
AB  - Molindone hydrochloride (Moban) is a dihydroindolone compound dissimilar in
      structure to other antipsychotic drugs (i.e., phenothiazines, butyrophenones,
      dibenzepines, and thioxanthenes). The antipsychotic (or neuroleptic) activity of
      molindone makes it particularly useful in the treatment of schizophrenia. There
      are a few published cases which report the tissue distribution of molindone in
      the human body. We report the analysis of molindone in postmortem samples using a
      solvent mixture (toluene/hexane/isoamyl alcohol) base extract followed by an acid
      (0.5M H(2)SO(4)) wash. Molindone was identified by gas chromatography-mass
      spectrometry (m/z 100, 176, 276) and quantitated using a gas chromatograph and
      nitrogen-phosphorus detector. The range of linearity was 0.1 mg/L to 5.0 mg/L. We
      report our findings of molindone concentrations in blood, liver, bile, gastric,
      and urine as follows: 6 mg/L in blood; 26 mg/kg in liver; 23.1 mg/L in bile; 1200
      mg/L in gastric; and 37.3 mg/L in urine. Vitreous lithium (5.9 mmol/L) was
      determined by flame atomic absorption spectrometry. The medical examiner listed
      the cause of death as a combined drug overdose of molindone and lithium. The
      tissue results are compared with another case and the pharmacology of molindone
      is presented.

PMID- 15516312
TI  - Metaxalone (Skelaxin)-related death.
AB  - The case history and toxicological findings of a fatal multi-drug overdose
      involving metaxalone (Skelaxin) are presented. Gas-liquid chromatography with
      flame-ionization detection and gas chromatography-mass spectrometry were used to
      determine the following drug concentrations (mg/L) in aortic blood: 19 mg/L
      metaxalone; 190 mg/L acetaminophen; 0.28 mg/L hydrocodone; and < 0.1 mg/L
      diazepam, nordiazepam, amitriptyline, and nortriptyline. The following
      concentrations of metaxalone were reported in alternate specimens: 17 mg/L in
      femoral blood; 44 mg/L in bile; 70 mg/kg in liver; 7 mg/L in urine; 202 mg/kg in
      gastric contents; and 14 mg/L in vitreous humor. These concentrations were
      determined using both direct extraction and the method of standard addition. The
      quantitative results obtained by both procedures were in good agreement. Because
      of the limited information published on metaxalone toxicity, the pathologist
      assigned the manner and cause of death as accidental acute hydrocodone
      intoxication. Four additional cases in which metaxalone was present were analyzed
      for comparison. Two cases were probable drug-related deaths and had metaxalone
      aorta blood concentrations of 18 and 11 mg/L. The other two cases had therapeutic
      metaxalone concentrations in the aortic blood of < 0.75 and 2.1 mg/L.

PMID- 15516313
TI  - Passive cannabis smoke exposure and oral fluid testing.
AB  - Oral fluid testing for Delta(9)-tetrahydrocannabinol (THC) provides a convenient
      means of detection of recent cannabis usage. In this study, the risk of positive
      oral fluid tests from passive cannabis smoke exposure was investigated by housing
      four cannabis-free volunteers in a small, unventilated, and sealed room with an
      approximate volume of 36 m(3). Five active cannabis smokers were also present in
      the room, and each smoked a single cannabis cigarette (1.75% THC). Cannabis
      smoking occurred over the first 20 min of the study session. All subjects
      remained in the room for approximately 4 h. Oral fluid specimens were collected
      with the Intercept DOA Oral Specimen Collection Device. Three urine specimens
      were collected (0, 20, and 245 min). In addition, three air samples were
      collected for measurement of THC content. All oral fluid specimens were screened
      by enzyme immunoassay (EIA) for cannabinoids (cutoff concentration = 3 ng/mL) and
      tested by gas chromatography-tandem mass spectrometry (GC-MS-MS) for THC (LOQ/LOD
      = 0.75 ng/mL). All urine specimens were screened by EIA for cannabinoids (cutoff
      concentration = 50 ng/mL) and tested by GC-MS-MS for THCCOOH (LOQ/LOD = 1 ng/mL).
      Air samples were measured for THC by GC-MS (LOD = 1 ng/L). A total of eight oral
      fluid specimens (collected 20 to 50 min following initiation of smoking) from the
      four passive subjects screened and confirmed positive for THC at concentrations
      ranging from 3.6 to 26.4 ng/mL. Two additional specimens from one passive
      subject, collected at 50 and 65 min, screened negative but contained THC in
      concentrations of 4.2 and 1.1 ng/mL, respectively. All subsequent specimens for
      passive participants tested negative by EIA and GC-MS-MS for the remainder of the
      4-h session. In contrast, oral fluid specimens collected from the five cannabis
      smokers generally screened and confirmed positive for THC throughout the session
      at concentrations substantially higher than observed for passive subjects. Urine
      specimens from active cannabis smokers also screened and confirmed positive at
      conventional cutoff concentrations. A biphasic pattern of decline for THC was
      observed in oral fluid specimens collected from cannabis smokers, whereas a
      linear decline was seen for passive subjects suggesting that initial oral fluid
      contamination is cleared rapidly and is followed by THC sequestration in the oral
      mucosa. It is concluded that the risk of positive oral fluid tests from passive
      cannabis smoke inhalation is limited to a period of approximately 30 min
      following exposure.

PMID- 15516314
TI  - Development of a method for the detection and confirmation of the alpha-2 agonist
      amitraz and its major metabolite in horse urine.
AB  - Amitraz (N'-(2,4-dimethylphenyl)-N-[[(2,4-dimethylphenyl)imino]methyl]-N-methyl
      methanimidamide) is an alpha-2 adrenergic agonist used in veterinary medicine
      primarily as a scabicide- or acaricide-type insecticide. As an alpha-2 adrenergic
      agonist, it also has sedative/tranquilizing properties and is, therefore, listed
      as an Association of Racing Commissioners International Class 3 Foreign
      Substance, indicating its potential to influence the outcome of horse races. We
      identified the principal equine metabolite of amitraz as N-2,4-dimethylphenyl-N'
      methylformamidine by electrospray ionization(+)-mass spectrometry and developed a
      gas chromatographic-mass spectrometric (GC-MS) method for its detection,
      quantitation, and confirmation in performance horse regulation. The GC-MS method
      involves derivatization with t-butyldimethylsilyl groups; selected ion monitoring
      (SIM) of m/z 205 (quantifier ion), 278, 261, and 219 (qualifier ions); and
      elaboration of a calibration curve based on ion area ratios involving
      simultaneous SIM acquisition of an internal standard m/z 208 quantifier ion based
      on an in-house synthesized d(6) deuterated metabolite. The limit of detection of
      the method is approximately 5 ng/mL in urine and is sufficiently sensitive to
      detect the peak urinary metabolite at 1 h post dose, following administration of
      amitraz at a 75-mg/horse intravenous dose.

PMID- 15516315
TI  - Amphetamine excretion profile following multidose administration of mixed salt
      amphetamine preparation.
AB  - Interpretation of drug testing results requires detailed scientific information,
      particularly in those cases where the question of legitimate use versus illicit
      use arises. Amphetamine remains a widely abused drug throughout the world,
      although it is also used therapeutically for weight loss, narcolepsy, and
      attention-deficit disorder with hyperactivity (ADHD). Treatment of ADHD using
      stimulant drugs is much more common now than it was in even the recent past.
      Increasingly, older individuals are diagnosed and treated for ADHD, and treatment
      often continues into adulthood. Amphetamine is commonly used for the treatment of
      ADHD and is available by prescription as either the d-enantiomer or a mixture of
      enantiomers. Although used for many years, there are no data available to
      describe the excretion profile of amphetamine and its enantiomers following
      repeated use of the drug. As a result, medical review officers (MROs) and
      forensic toxicologists have no direct evidence to base their decisions on when it
      comes to evaluation of use of these drugs. The current study was designed to
      determine the concentration and enantiomer excretion profile following repeated
      daily administration of mixed enantiomers of amphetamine. Twenty milligrams of
      Adderall was administered daily to five healthy subjects with all subsequent ad
      lib urine samples collected for at least five days following administration of
      the five-dose regimen. Adderall is a 3:1 mixture of d- and l-enantiomers of
      amphetamine salts and represents the mixed enantiomer proportion of amphetamine
      available in the United States through pharmaceutical channels. Peak amphetamine
      concentrations ranged from 5739 to 19,172 ng/mL. Samples containing > or = 500
      ng/mL amphetamine (the administrative cutoff for a positive result by gas
      chromatography-mass spectrometry) were seen up to 60:15 (h:min) following
      administration of the last dose. Enantiomer analysis showed the d-enantiomer to
      be in excess of the l-enantiomer for as long as the drug was administered. After
      administration of the last dose of drug, the proportion of l-enantiomer increased
      over time. Not all samples that contained > or = 500 ng/mL total amphetamine were
      positive when tested by immunoassay because of the differing cross-reactivity of
      the enantiomers. This study provides the first description of the excretion of
      amphetamine following repeated administration of Adderall. The presence of the l
      enantiomer separates this drug from other formulations composed of only the d
      enantiomer (i.e., Dexedrine and much illicit amphetamine), thus readily
      differentiating them from Adderall use. Some illicit and medicinal amphetamine
      is, however, a mixture of amphetamine enantiomers. Because the enantiomers are
      metabolized at different rates, their proportion offers the opportunity to
      describe excretion versus time. Coupling this data with drug concentration makes
      it possible for forensic toxicologists and MROs to come to an informed decision
      regarding the involvement of this drug in a positive drug test result.

PMID- 15516316
TI  - Analysis of phthalate contamination in infusion solutions by automated on-line in
      tube solid-phase microextraction coupled with high-performance liquid
      chromatography.
AB  - Contamination of infusion solutions with phthalates was analyzed, and its origin
      was determined. Phthalates were determined by on-line in-tube solid-phase
      microextraction coupled with high-performance liquid chromatography (in-tube SPME
      HPLC) with UV detection. In-tube SPME is an extraction technique for organic
      compounds in aqueous samples, in which analytes are extracted from the sample
      directly into an open tubular capillary by repeated draw/eject cycles of sample
      solution. The infusion solutions were used without any pretreatment, and the
      phthalates in these solutions were automatically analyzed by the on-line in-tube
      SPME-HPLC system. The limits of detection of phthalates in the infusion solutions
      were 1-10 ng/mL. With a few exceptions, the recoveries of phthalates added to the
      infusion solutions were above 80%. Di-n-butyl phthalate (DBP) was detected at a
      concentration of 7-60 ng/mL in most infusion solutions in plastic containers but
      was not detected in those in glass bottles. On the other hand, no other
      phthalates were detected in infusion solutions in either plastic or glass
      containers. Large amounts of DBP were detected in the adhesive used to affix the
      paper labels to the plastic bottles and bags, but not in the plastic containers
      themselves. Furthermore, DBP was shown to be readily eluted from the adhesive
      into water and alcohol and easily pass through the plastic. These results
      indicated that the source of the DBP was the adhesive used to affix the paper
      labels, and DBP contaminated the infusion solutions by passing through the
      plastic. The in-tube SPME-HPLC method is simple and rapid and provides a useful
      tool for the screening and determination of phthalate contamination in infusion
      solutions.

PMID- 15516317
TI  - Determination of a bound musk xylene metabolite in carp hemoglobin as a biomarker
      of exposure by gas chromatography-mass spectrometry using selected ion
      monitoring.
AB  - Musk xylene (MX) is widely used as a fragrance ingredient in commercial
      toiletries. Identification and quantitation of a bound 4-amino-MX (AMX)
      metabolite was carried out by gas chromatography-mass spectrometry (GC-MS) with
      selected ion monitoring (SIM). Detection of AMX occurred after the cysteine
      adducts in carp hemoglobin (Hb), derived from the nitroso metabolite, were
      released by alkaline hydrolysis. The released AMX metabolite was extracted into n
      hexane. The extract was preconcentrated by evaporation and analyzed by GC-SIM-MS.
      The concentration of AMX metabolite was found to range from 6.0 to 30.6 ng/g in
      the carp Hb, collected from the Las Vegas Wash and Lake Mead, NV areas. The
      presence of an AMX metabolite in the carp Hb was confirmed when similar mass
      spectral features and the same retention time of the AMX metabolite were obtained
      for both standard AMX and carp Hb extract solutions. In the nonhydrolyzed and
      reagent blank extracts, the AMX metabolite was not detected.

PMID- 15516318
TI  - Determination of the benzodiazepine plasma concentrations in suicidal patients
      using a radioreceptor assay.
AB  - Impairments in memory and psychomotor function appear to be induced by
      benzodiazepines not only after long-term use, but also after administration of a
      single dose. Because it is known on which neurotransmitter system the
      benzodiazepines exert their action, the use of a quantitative radioreceptor assay
      (RRA) can be a useful tool in studying the interrelationship between the
      neurochemical and memory processes. The RRA measures the sum of the main
      compound(s) and all active metabolites present, where it relates the biological
      activity to the pharmacodynamic effect instead of relating it to the plasma
      levels of the individual compounds. To correlate the loss of memory with the
      benzodiazepine concentration, plasma concentrations were determined in suicidal
      patients. From suicidal patients (n = 84), the benzodiazepines in plasma were
      measured with a direct radioreceptor assay using tritiated flunitrazepam as the
      labelled ligand. The receptor material was a lyophilized preparation from calf
      cortex. Furthermore, the samples were subjected to high-performance liquid
      chromatographic (HPLC) analysis, and the HPLC data were converted to diazepam
      equivalents using cross-reactivities of the individual compounds. Patients who
      had ethanol residues in their plasma were excluded from this correlation
      experiment. The data (n = 40) obtained with the two analytical techniques were
      compared and correlated to assess the validity of the radioreceptor assay in
      establishing the relationship between the loss of memory and the total amount of
      benzodiazepines present. The cumulative amount of diazepam determined with the
      RRA and the sum of compounds determined with the HPLC method, after correction
      using the cross-reactivities, were plotted and correlated using regression
      analysis. Regression analysis showed an x variable of 0.75 and a correlation
      coefficient of 0.67. The intercept was not significantly different from zero (P =
      0.49, t-test), whereas the slope was significantly different from zero (P <
      0.01). Benzodiazepines can be directly determined in plasma using this
      radioreceptor assay. The data obtained from HPLC analysis were easily converted
      to diazepam equivalents using the cross-reactivities. A discrepancy between the
      data obtained from the two analytical techniques, however, indicates that certain
      metabolites are present, which were not quantitated in the HPLC analysis, but
      were measured in the radioreceptor assay. Therefore, the radioreceptor assay
      proved to be a valuable tool for the assessment of clinical effects, such as the
      demonstration of the loss of memory in suicidal patients after a benzodiazepine
      overdose.

PMID- 15516319
TI  - Evaluation of Roche Diagnostics ONLINE DAT II, a new generation of assays for the
      detection of drugs of abuse.
AB  - A new generation of ONLINE assays has been developed that offers improved
      performance and enhanced ease of use. This family of assays is being applied to
      both the COBAS INTEGRA and Roche/Hitachi line of analyzers. The four ONLINE DAT
      II assays that were evaluated included cocaine (benzoylecgonine) (BE), methadone
      (MDN), opiates (OP), and tetrahydrocannabinol (THC). The BE assay has a dual
      cutoff (150/300 ng/mL) with a dynamic range from 0 to 5000 ng/mL. The MDN assay
      has a cutoff of 300 ng/mL with a dynamic range from 0 to 2000 ng/mL. The opiates
      assay has a 300 ng/mL cutoff with a 0 to 2000 ng/mL range and a 2000 ng/mL cutoff
      with a 0 to 8000 ng/mL range. The THC assay has 20, 50, and 100 ng/mL cutoffs
      with 0 to 100, 0 to 300, and 0 to 300 ng/mL dynamic ranges, respectively. The
      ranges of the intra-assay precision (coefficients of variation for n = 20) run in
      the semiquantitative mode are 2.3-7.5% for BE, 2.0-3.8% for MDN, 1.9-4.2% for OP,
      and 3.9-5.2% for THC. The intra-assay qualitative precision for all of the assays
      as calculated from absorbance values is generally higher than that of the intra
      assay semiquantitative precision at the cutoff. The qualitative precision ranges
      between 0.4% and 3.1%. The standard curve stability defined for the COBAS INTEGRA
      systems for these reagents ranges from 35 to 68 days. The clinical sensitivity
      and specificity were compared to the OnLine generation I and CEDIA immunoassays,
      as well as gas chromatography-mass spectrometry (GC-MS). The results indicate
      that for each assay, the sensitivity and specificity were the same or greater
      when compared to the other two immunoassay technologies. The results of each
      assay also correlated very well (> 99%) when compared with GC-MS.

PMID- 15516320
TI  - Six spectroscopic methods for detection of oxidants in urine: implication in
      differentiation of normal and adulterated urine.
AB  - Six separate methods to detect oxidants in urine were developed. The presence of
      the oxidants was established by initial oxidation of ferrous to ferric ion and
      detecting the ferric by chromogenic oxidation or complex formation. The reagents
      for chromogenic oxidation were N,N-dimethylamoino-1,4-phenylenediamine (DMPDA),
      2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid (ABTS), and 2-amino-p-cresol
      (APC), and the reagents for the chromogenic complex were xylenol orange (XO), 8
      hydroxy-7-iodo-5-quinolinesulfonic acid (HIQSA), and 4,5-dihydroxy-1,3-benzene-di
      sulfonic acid (HBSA). All methods showed comparable results when tested for
      ferric, chromate, permanganate, oxychloride, hydrogen peroxide, oxone, tert
      butylhydroperoxide, and cumenehydroperoxide at a concentration of 1.0 mmol/L in
      water (CV < 7%). The nitrite results are comparable only with DMPDA and APC.
      Periodate responded to the highest oxidation number (ON = 8) by chromogenic
      oxidation but lowest (ON = 2) by the chromogenic complex. The iodate responded
      only to the chromogenic oxidation with ON = 6. The linearity of the procedures
      was established by chromate in water. The linear concentrations were 0.09-12.00
      mE/L for DMPDA, ABTS, APC, and HBSA and 0.09-6.00 mE/L for XO and HIQSA. In all
      methods, the correlation coefficients were > or = 0.9991 and precisions were
      within +/- 5.6%. The methods were used to test oxidants in 238 urine specimens.
      The chromate at 3.0 mE/L in water was used as standard. The correlation
      coefficients of 0.9600-0.9853 and the ANOVA test (F = 0.90, F(critical) = 2.22 at
      P(0.48)) indicated that the methods correlated well. The median concentration of
      oxidants in the specimens was 0.21 mE/L with an average and standard deviation of
      0.62 +/- 1.19 (range 0.04-8.83 mE/L). When Grubbs' statistical test was applied
      to the specimen results, no specimen was found to be outlier or could be
      considered as adulterated. The Grubbs' test also revealed that the threshold
      concentration to identify urine adulteration was 29 mE/L at confidence level of
      99%.

PMID- 15516321
TI  - Attempted suicide by ingestion of chlorpyrifos: identification in serum and
      gastric content by GC-FID/GC-MS.
AB  - A mild case of self-poisoning with a chlorpyrifos formulation following oral
      ingestion is reported. A 15-year-old female went to the emergency room after the
      ingestion of a product from a bottle marked with a label "Poison". On admission,
      she was obtunded, with normal vital signs and a strong smell of solvent.
      Therapeutic measures included the application of decontamination procedures,
      oxygen, and gastric protectors. She had a good outcome with mild CNS depression
      and bradycardia. Two hours after ingestion, biological samples were collected in
      the emergency room and sent for analysis to our laboratory with instructions to
      investigate the presence of solvents. The serum and gastric content contained 5.3
      and 9.4 microg/mL of unmetabolized chlorpyrifos, 4.6 and 6.9 microg/mL of
      toluene, and 2.5 and 7.9 microg/mL of butyl acetate, respectively. Small traces
      of other solvents and tetradifon were also detected. Toxicological analyses were
      negative for ethanol, other volatile solvents, and common drugs of abuse. The
      simultaneous determination of chlorpyrifos, toluene, and butyl acetate was
      performed using the combination of gas chromatography (GC)-flame ionization
      detection for screening analysis and GC-mass spectrometry for confirmation of the
      obtained results. The method provides an excellent and rapid tool for use in
      cases of pesticide poisonings, allowing the simultaneous detection of the
      pesticide and distillates in the performance of systematic toxicological analysis
      in forensic and clinical laboratories.

PMID- 15516322
TI  - Oxycodone involvement in drug abuse deaths. II. Evidence for toxic multiple drug
      drug interactions.
AB  - Recent surveys suggest that the abuse of drugs, often in combination, is
      pervasive throughout society. Adverse consequences of drug abuse tend to be
      attributed to the single drug "most likely" to be responsible. This is frequently
      seen in fatality cases, particularly those involving opioids. However, it is
      difficult to determine the specific cause of death when multiple drugs are
      involved. Although enhanced toxicity of alcohol and other centrally acting drugs
      with opioids has been well established in animal studies, there is a paucity of
      data in well-controlled human studies. We evaluated 1014 fatality cases involving
      oxycodone (OXC) for evidence of enhanced toxicity associated with multiple drug
      drug interactions. We previously reported on these cases, and we classified them
      by a standardized method into groups that distinguished cases unrelated to drug
      abuse from those related to drug abuse, cases that involved only OXC from cases
      involving multiple drugs, drug-induced fatalities from drug-related fatalities,
      and cases in which the specific drug product OxyContin (oxycodone HCl controlled
      release) Tablets were identified from cases where OxyContin was not identified.
      Our working hypothesis was that OXC in combination with other centrally acting
      drugs is more toxic than OXC alone, evidenced by the finding of lower mean blood
      concentrations of OXC in multiple-drug-induced deaths compared to single (OXC
      only)-drug-induced deaths. Assessment of blood levels determined by specific
      assay methodology (primarily gas chromatography-mass spectrometry) in these cases
      provided the following mean postmortem concentrations of OXC: multiple-drug
      induced deaths, OxyContin identified, 0.93 microg/mL (N = 167); multiple-drug
      induced deaths, OxyContin not identified, 0.73 microg/mL (N = 579); single (OXC)
      drug-induced deaths, OxyContin identified, 1.55 microg/mL (N = 12); and single
      (OXC)-drug-induced deaths, OxyContin not identified, 1.70 microg/mL (N = 15).
      Overall, mean OXC concentration trends were as follows: single (OXC)-drug
      induced, drug-abuse deaths > multiple-drug-induced drug-abuse deaths > drug
      related drug-abuse deaths approximately deaths unrelated to drug abuse; and
      deaths in which OxyContin was identified approximately deaths in which OxyContin
      was not identified, whether the deaths involved oxycodone alone or multiple
      drugs. Drug abuse patterns in the multiple-drug-induced cases were complex. Over
      135 drugs that were considered to be plausibly contributory to enhanced toxicity
      were identified in body fluids and tissues. Evaluation of mean OXC blood
      concentrations in cases that contained one, two, three, four, five, and six or
      more contributory drugs in combination demonstrated consistently lower mean OXC
      concentrations than those cases in which OXC was the only drug identified. A
      smaller number of cases were evaluated in the multiple-drug-induced groups in
      which OXC was paired with a single other contributory drug. The overall mean OXC
      concentration for these cases was 0.71 microg/mL (N = 90) as compared to 1.64
      microg/mL (N = 27) for the cases in the single drug-induced groups. The
      consistent finding of lower mean OXC blood levels associated with multiple-drug
      induced fatalities supports the stated hypothesis that OXC in combination with
      other centrally active drugs is more toxic than when OXC was the only drug
      involved. It was concluded that in cases of multiple-drug fatalities, cause of
      death (COD) should not be attributed to any single drug. Rather, the unique
      combination of drugs, the pattern of drug use/abuse, and individual factors, such
      as tolerance to the respiratory depressant effects of opioids, must be taken into
      account in arriving at a valid COD statement.

PMID- 15516323
TI  - Effect of TNF-alpha on human osteosarcoma cell line Saos2--TNF-alpha regulation
      of bone sialoprotein gene expression in Saos2 osteoblast-like cells.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a major mediator of inflammatory
      response in many diseases. It inhibits bone formation and stimulates bone
      resorption. To determine the molecular mechanisms involved in the regulation of
      gene expression of osteoblast-like cells, we analyzed the effects of TNF-alpha on
      the human osteosarcoma cell line Saos2. We used RT-PCR to examine the effects of
      TNF-alpha on bone sialoprotein (BSP), core binding factor a1 (Cbfa1), osterix,
      alpha 1 (I) collagen, cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), cathepsin
      B, cathepsin L and tissue inhibitors of metalloproteinase-1 (TIMP-1). TNF-alpha
      (10ng/ml) increased BSP, IL-6 and COX-2 mRNA levels after 3h, reaching maximal
      levels at 12 h. Cbfa1 mRNA levels increased after 3 h, but decreased by 24 h.
      Osterix, cathepsin B, cathepsin L and TIMP-1 mRNA levels did not change after
      stimulation with TNF-alpha. On the other hand, alpha 1 (I) collagen mRNA
      expression was suppressed by TNF-alpha at 24 h. Transient transfection analyses
      were performed using chimeric constructs of the rat BSP gene promoter linked to a
      luciferase reporter gene. TNF-alpha (10 ng/ml) had no effect on the promoter
      activities of BSP transfected into Saos2 cells. The results of gel mobility shift
      assays using radiolabeled double-stranded cAMP response element (CRE) and FGF2
      response element (FRE) oligonucleotides in the proximal promoter of the rat BSP
      gene showed increased binding of nuclear proteins at 6 h. Gel mobility shift
      assays with radiolabelled COX-2-CRE and COX-2-NF kappa B oligonucleotides
      revealed an increase in the binding of nuclear proteins from TNF-alpha-stimulated
      Saos2 cells. These studies, therefore, showed that TNF-alpha indirectly increased
      BSP expression, and that it could be mediated through COX-2 and Cbfa1 expression
      in Saos2 osteoblast-like cells.

PMID- 15516324
TI  - Expression of PTHrP and the PTH/PTHrP receptor in growing red deer antler.
AB  - Antler growth is highly co-ordinated, so that trabecular bone and antler skin
      (velvet) develop together, at a rapid rate and in a manner reminiscent of their
      development in the fetus. Parathyroid hormone-related peptide (PTHrP) is
      expressed in both bone and skin, and is therefore a candidate to effect co
      ordination between these tissues. The aim of this study was to localize the
      expression of PTHrP and its principal receptor, the parathyroid
      hormone/parathyroid hormone-related peptide receptor (PTH/PTHrPR), in antler
      ("spiker") of one-year-old red deer. Using immunohistochemistry and in situ
      hybridization, intense and overlapping expression of PTHrP and its receptor was
      seen in developing osseocartilaginous structures and in the underlying layers of
      velvet epidermis. PTHrP was located on both the cell surface and within the
      nuclei. Our results strongly suggest that PTHrP, acting via the PTH/PTHrPR and
      possibly other intracrine mechanisms, plays a central role in the co-ordinated
      regulation of cell division and differentiation of developing antler bone and
      skin.

PMID- 15516325
TI  - Effect of bone morphogenetic proteins-4, -5 and -6 on DNA synthesis and
      expression of bone-related proteins in cultured human periodontal ligament cells.
AB  - Bone morphogenetic proteins (BMPs) have multiple functions in the development and
      growth of skeletal and extraskeletal tissues. Therefore, BMPs may regulate the
      regeneration of periodontal tissue. To investigate this issue, we examined the
      effects of BMP-4, -5 and -6 on DNA synthesis and the expression of bone-related
      proteins in cultures of human periodontal ligament (HPL) cells. The expression of
      bone-related proteins was determined by Real-time polymerase chain reaction and
      enzyme linked immunosorbent assay in cultures of HPL cells. DNA synthesis was
      estimated by measuring bromoderoxyuridine incorporation. It was found that BMP-4,
      -5 and -6 enhanced DNA synthesis dose-dependently. BMP-4 and -5 increased the
      levels of osteopontin, BMP-2, alkaline phosphatase and core binding factor alpha
      1 mRNAs. BMP-6 stimulated the expression of osteopontin, BMP-2, ALPase and
      osteoprotegerin. These findings show that BMP-4, -5 and -6 have different actions
      on the expression of bone-related proteins and may play a role in the
      regeneration of periodontal tissue by promoting cell proliferation and protein
      expression.

PMID- 15516326
TI  - Low power microwave interaction with phospholipase C and D signal transduction
      pathways in myogenic cells.
AB  - Ionic channel proteins are possible sites of microwave interaction at the cell
      membrane level. Patch-clamp data, using single channel and total current
      recording, indicated that low level microwave fields may modify some functional
      parameters of the nicotinic acetylcholine receptor in primary chick myotubes,
      suggesting a possible effect of microwaves on myogenic cells. Here, we
      investigated the biological relevance of such results, in relation to the
      possible involvement of intracellular signaling processes. We exposed L6-C5
      myogenic cells to low power electromagnetic fields and observed the consequences
      on hormonal activation of phospholipases C and D. We found that increased
      inositol phospholipid turnover, induced by acetylcholine and arginine vasopressin
      activation of phospholipase C, was not modified in microwave irradiated myoblasts
      or myotubes. Moreover, vasopressin-dependent phospholipase D activation, assessed
      by measuring the [3H]-free choline release, was not modified by microwave
      irradiation. Our conclusions suggest that low level microwave fields do not
      modify signal transduction pathways activated by acetylcholine and vasopressin in
      L6-C5 myogenic cells.

PMID- 15516327
TI  - Expression and regulation of interleukin-23 subunits in human peripheral blood
      mononuclear cells and hematopoietic cell lines in response to various inducers.
AB  - IL-23 is a novel cytokine composed of an IL-12 p40 and a p19 subunit. We analyzed
      human peripheral blood mononuclear cells (PBMC) and hematopoietic cell lines for
      constitutive expression of IL-23 and IL-12 subunits and expression following
      exposure to various stimuli, and investigated the mechanisms of their induction
      by LPS and SAC. IL-23 p19 and IL-12 p35 mRNAs were expressed in fresh PBMC, and
      expression of all IL-23 and IL-12 subunits was up-regulated by LPS and SAC. LPS
      induced increase of IL-23 and IL-12 subunits expression was CD14-dependent, while
      CD14 was not involved in SAC-induced p19 transcription. Both LPS- and SAC-induced
      subunits expression required p38 MAPK pathway. PHA effected an increase of p19
      mRNA in both CD4+ and CD8+ T cells, whereas p35 was minimally regulated by PHA.
      IFN-gamma primed monocytes for LPS stimulation of p19, p35 and p40 expression.
      p19 mRNA was detectable in most hematopoietic cell lines tested but p35
      distribution was more restricted. A phorbol diester enhanced p19, p35 and p40
      expression in EBV-positive cell lines. Our results suggest that both the subunits
      of IL-23 are tightly regulated; the expression pattern and regulation mode of IL
      23 p19 is similar to as well as distinct from that of IL-12 p35.

PMID- 15516328
TI  - Structure, isolation, composition and reconstitution of the neuronal fusion pore.
AB  - Neuronal communication is dependent on the fusion of 40-50 nm in diameter
      synaptic vesicles containing neurotransmitters, at the presynaptic membrane. Here
      we report for the first time at 5-8A resolution, the presence of 8-10 nm in
      diameter cup-shaped neuronal fusion pores or porosomes at the presynaptic
      membrane, where synaptic vesicles dock and fuse to release neurotransmitters. The
      structure, isolation, composition, and functional reconstitution of porosomes
      present at the nerve terminal are described. These findings reveal the molecular
      mechanism of neurotransmitter release at the presynaptic membrane of nerve
      terminals.

PMID- 15516329
TI  - Vesicle swelling regulates content expulsion during secretion.
AB  - The involvement of secretory vesicle swelling has been proposed in secretion;
      however, little is known about its role. Using both the pancreatic acinar cell
      and neuronal model, we show secretory vesicle swelling in live cells. Our study
      reveals that vesicle swelling potentiates its fusion at the cell plasma membrane,
      and is required for expulsion of intravesicular contents. Since the extent of
      swelling is directly proportional to the amount of vesicular contents expelled,
      this provides cells with the ability to regulate release of secretory products.
      These direct observations of the requirement of secretory vesicle swelling in
      secretion, provides an understanding of the appearance of partially empty
      vesicles following the process.

PMID- 15516330
TI  - Cholesterol esterification in human monocyte-derived macrophages is inhibited by
      protein kinase C with dual roles for mitogen activated protein kinases.
AB  - The possible role of protein kinase C (PKC) and mitogen activated protein (MAP)
      kinases in the stimulation of cholesterol esterification by acetylated low
      density lipoprotein (acLDL) in human monocyte-derived macrophages (HMDM) was
      studied. Cholesterol esterification, as assessed by the rate of incorporation of
      [3H]-oleate into cholesteryl ester, was markedly higher in HMDM incubated with
      acLDL as compared to native LDL (nLDL). In the presence of the phorbol ester,
      phorbol 12-myristate 13-acetate (PMA, 100 nM), however, the rate of incorporation
      was reduced by about 50% and 85% in incubations with nLDL and acLDL,
      respectively. Thus, the difference in the rate of cholesteryl esterification
      induced by the two types of lipoprotein was abolished by PMA, indicating that PKC
      activation inhibits the process, and this was confirmed by the finding that the
      PKC inhibitor calphostin C reversed the PMA-induced inhibition of cholesterol
      esterification. Incubation of HMDM with PMA was found to cause a considerable
      increase in the activation of p42/44 extracellular signal-regulated MAP kinases
      (ERK) and p38 MAP kinases, reaching a maximum at 30 min. In the presence of
      acLDL, the ERK inhibitor PD98059 decreased cholesterol esterification in HMDM by
      about 35%. In contrast, the p38 inhibitor SB203580 had no effect. However, when
      PMA was present in addition to SB203580, esterification was reduced to a level
      lower than that observed with PMA alone. These findings suggest that activation
      of ERK, but not p38, MAP kinases is involved in the induction of cholesterol
      esterification by acLDL in HMDM, while p38 MAP kinases may modulate the
      inhibitory effect of PKC, and thus provide evidence that MAP kinases play a role
      in the regulation of foam cell formation in human macrophages.

PMID- 15516331
TI  - Lower maternal PLAC1 mRNA in pregnancies complicated with vaginal bleeding
      (threatened abortion <20 weeks) and a surviving fetus.

PMID- 15516332
TI  - Differential stability of biogenesis intermediates reveals a common pathway for
      aquaporin-1 topological maturation.
AB  - Topological studies of multi-spanning membrane proteins commonly use sequentially
      truncated proteins fused to a C-terminal translocation reporter to deduce
      transmembrane (TM) segment orientation and key biogenesis events. Because these
      truncated proteins represent an incomplete stage of synthesis, they transiently
      populate intermediate folding states that may or may not reflect topology of the
      mature protein. For example, in Xenopus oocytes, the aquaporin-1 (AQP1) water
      channel is cotranslationally directed into a four membrane-spanning intermediate,
      which matures into the six membrane-spanning topology at a late stage of
      synthesis (Skach, W. R., Shi, L. B., Calayag, M. C., Frigeri, A., Lingappa, V.
      R., and Verkman, A. S. (1994) J. Cell Biol. 125, 803-815 and Lu, Y., Turnbull, I.
      R., Bragin, A., Carveth, K., Verkman, A. S., and Skach, W. R. (2000) Mol. Biol.
      Cell 11, 2973-2985). The hallmark of this process is that TM3 initially acquires
      an Nexo/Ccyto (Type I) topology and must rotate 180 degrees to acquire its mature
      orientation. In contrast, recent studies in HEK-293 cells have suggested that TM3
      acquires its mature topology cotranslationally without the need for reorientation
      (Dohke, Y., and Turner, R. J. (2002) J. Biol. Chem. 277, 15215-15219). Here we re
      examine AQP1 biogenesis and show that irrespective of the reporter or fusion site
      used, oocytes and mammalian cells yielded similar topologic results. AQP1
      intermediates containing the first three TM segments generated two distinct
      cohorts of polypeptides in which TM3 spanned the ER membrane in either an
      Ncyto/Cexo (mature) or Nexo/Ccyto (immature) topology. Pulse-chase analyses
      revealed that the immature form was predominant immediately after synthesis but
      that it was rapidly degraded via the proteasome-mediated endoplasmic reticulum
      associated degradation (ERAD) pathway with a half-life of less than 25 min in HEK
      cells. As a result, the mature topology predominated at later time points. We
      conclude that (i) differential stability of biogenesis intermediates is an
      important factor for in vivo topological analysis of truncated chimeric proteins
      and (ii) cotranslational events of AQP1 biogenesis reflect a common AQP1 folding
      pathway in diverse expression systems.

PMID- 15516333
TI  - [Ca2+]i signaling between mitochondria and endoplasmic reticulum in neurons is
      regulated by microtubules. From mitochondrial permeability transition pore to
      Ca2+-induced Ca2+ release.
AB  - The positioning and dynamics of organelles depend on membrane-cytoskeleton
      interactions. Mitochondria relocate along microtubules (MT), but it is not clear
      whether MT have direct effects on mitochondrial function. Using two-photon
      microscopy and the mitochondrial fluorescent dyes rhodamine 123 and Rhod-2, we
      showed that Taxol and nocodazole, which correspondingly stabilize and disrupt MT,
      decreased potential and Ca(2+) in the mitochondria of brain stem pre-Botzinger
      complex neurons. Without changing basal cytoplasmic Ca(2+) ([Ca(2+)](i)), Taxol
      promoted the generation of [Ca(2+)](i) spikes in dendrites. These spikes were
      abolished after blockade of Ca(2+) influx and after depletion of internal Ca(2+)
      stores, indicating the involvement of Ca(2+)-induced Ca(2+) release. Nocodazole
      decreased mitochondrial potential and [Ca(2+)](m) and produced a long lasting
      increase in [Ca(2+)](i). MT-acting drugs depolarized single immobilized
      mitochondria and released previously stored Ca(2+). All of these effects were
      inhibited by pretreatment with blockers of mitochondrial permeability transition
      pore (mPTP), cyclosporin A, and 2-aminoethoxydiphenyl borate. Induction of mPTP
      by Taxol and nocodazole was confirmed by using a calcein/Co(2+) imaging
      technique. Electron and optical microscopy revealed tubulin bound to
      mitochondria. Mitochondria, MT, and endoplasmic reticulum (ER) showed strong co
      localization, the degree of which decreased after MT were disrupted. We propose
      that changes in the structure of MT by Taxol and nocodazole promote the induction
      of mPTP. Subsequent Ca(2+) efflux stimulates the Ca(2+) release from the ER that
      drives spontaneous [Ca(2+)](i) transients. Thus, close positioning of
      mitochondria to the ER as determined by MT can be essential for the local [Ca](i)
      signaling in neurons.

PMID- 15516334
TI  - Epidermal peroxisome proliferator-activated receptor gamma as a target for
      ultraviolet B radiation.
AB  - Ultraviolet B radiation (UVB) is a pro-oxidative stressor with profound effects
      on skin in part through its ability to stimulate cytokine production. Peroxisome
      proliferator-activated receptor gamma (PPAR gamma) has been shown to regulate
      inflammatory processes and cytokine release in various cell types. Since the
      oxidized glycerophospholipid 1-hexadecyl-2-azelaoyl glycerophosphocholine (azPC)
      has been shown to be a potent PPAR gamma agonist, this study was designed to
      assess whether the PPAR gamma system is a target for UVB irradiation and involved
      in UVB-induced inflammation in epidermal cells. The present studies demonstrated
      the presence of PPAR gamma mRNA and functional protein in human keratinocytes and
      epithelial cell lines HaCaT, KB, and A431. The treatment of epidermal cells with
      the PPAR gamma-specific agonist ciglitazone or azPC augmented cyclooxygenase-2
      expression and enzyme activity induced by phorbol 12-myristate-13-acetate or
      interleukin-1 beta. Lipid extracts from the cell homogenate of UVB-irradiated,
      but not control, cells contained a PPAR gamma-agonistic activity identified by
      reporter assay, and this activity up-regulated cyclooxygenase-2 expression
      induced by phorbol 12-myristate-13-acetate. Subjecting purified 1-hexadecyl-2
      arachidonoyl-glycerophosphocholine to UVB irradiation generated a PPAR gamma
      agonistic activity, among which the specific PPAR gamma agonist azPC was
      identified by mass spectrometry. These findings suggested that UVB-generated PPAR
      gamma-agonistic activity was due to the free radical mediated non-enzymatic
      cleavage of endogenous glycerophosphocholines. Treatment with the specific PPAR
      gamma antagonist GW9662 or expression of a dominant-negative PPAR gamma mutant in
      KB cells inhibited UVB-induced epidermal cell prostaglandin E(2) production.
      These findings suggested that UVB-generated PPAR gamma activity is necessary for
      the optimal production of epidermal prostaglandins. These studies demonstrated
      that epithelial cells contain a functional PPAR gamma system, and this system is
      a target for UVB through the production of novel oxidatively modified endogenous
      phospholipids.

PMID- 15516335
TI  - Additivity in effects of vitronectin and monoclonal antibodies against alpha
      helix F of plasminogen activator inhibitor-1 on its reactions with target
      proteinases.
AB  - The serpin plasminogen activator inhibitor-1 (PAI-1) is a potential therapeutic
      target in cardiovascular and cancerous diseases. PAI-1 circulates in blood as a
      complex with vitronectin. A PAI-1 variant (N-((2-(iodoacetoxy)ethyl)-N
      methyl)amino-7-nitrobenz-2-oxa-3-diazole (NBD) P9 PAI-1) with a fluorescent tag
      at the reactive center loop (RCL) was used to study the effects of vitronectin
      and monoclonal antibodies (mAbs) directed against alpha-helix F (Mab-2 and MA
      55F4C12) on the reactions of PAI-1 with tissue-type and urokinase-type
      plasminogen activators. Both mAbs delay the RCL insertion and induce an increase
      in the stoichiometry of inhibition (SI) to 1.4-9.5. Binding of vitronectin to NBD
      P9 PAI-1 does not affect SI but results in a 2.0-6.5-fold decrease in the
      limiting rate constant (klim) of RCL insertion for urokinase-type plasminogen
      activator at pH 6.2-8.0 and for tissue-type plasminogen activator at pH 6.2.
      Binding of vitronectin to the complexes of NBD P9 PAI-1 with mAbs results in a
      decrease in klim and in a 1.5-22-fold increase in SI. Thus, vitronectin and mAbs
      demonstrated additivity in the effects on the reaction with target proteinases.
      The same step in the reaction mechanism remains limiting for the rate of RCL
      insertion in the absence and presence of Vn and mAbs. We hypothesize that
      vitronectin, bound to alpha-helix F on the side opposite to the epitopes of the
      mAbs, potentiates the mAb-induced delay in RCL insertion and the associated
      substrate behavior by selectively decreasing the rate constant for the inhibitory
      branch of PAI-1 reaction (ki). These results demonstrate that mAbs represent a
      valid approach for inactivation of vitronectin-bound PAI-1 in vivo.

PMID- 15516336
TI  - Structural and mechanistic analysis of sialic acid synthase NeuB from Neisseria
      meningitidis in complex with Mn2+, phosphoenolpyruvate, and N
      acetylmannosaminitol.
AB  - In Neisseria meningitidis and related bacterial pathogens, sialic acids play
      critical roles in mammalian cell immunity evasion and are synthesized by a
      conserved enzymatic pathway that includes sialic acid synthase (NeuB, SiaC, or
      SynC). NeuB catalyzes the condensation of phosphoenolpyruvate (PEP) and N
      acetylmannosamine, directly forming N-acetylneuraminic acid (or sialic acid). In
      this paper we report the development of a coupled assay to monitor NeuB reaction
      kinetics and an 18O-labeling study that demonstrates the synthase operates via a
      C-O bond cleavage mechanism. We also report the first structure of a sialic acid
      synthase, that of NeuB, revealing a unique domain-swapped homodimer architecture
      consisting of a (beta/alpha)8 barrel (TIM barrel)-type fold at the N-terminal end
      and a domain with high sequence identity and structural similarity to the ice
      binding type III antifreeze proteins at the C-terminal end of the enzyme. We have
      determined the structures of NeuB in the malate-bound form and with bound PEP and
      the substrate analog N-acetylmannosaminitol to 1.9 and 2.2 A resolution,
      respectively. Typical of other TIM barrel proteins, the active site of NeuB is
      located in a cavity at the C-terminal end of the barrel; however, the positioning
      of the swapped antifreeze-like domain from the adjacent monomer provides key
      residues for hydrogen bonding with substrates in the active site of NeuB, a
      structural feature that leads to distinct modes of substrate binding from other
      PEP-utilizing enzymes that lack an analogous antifreeze-like domain. Our
      observation of a direct interaction between a highly ordered manganese and the N
      acetylmannosaminitol in the NeuB active site also suggests an essential role for
      the ion as an electrophilic catalyst that activates the N-acetylmannosamine
      carbonyl to the addition of PEP.

PMID- 15516337
TI  - Varied mechanisms underlie the free sialic acid storage disorders.
AB  - Salla disease and infantile sialic acid storage disorder are autosomal recessive
      neurodegenerative diseases characterized by loss of a lysosomal sialic acid
      transport activity and the resultant accumulation of free sialic acid in
      lysosomes. Genetic analysis of these diseases has identified several unique
      mutations in a single gene encoding a protein designated sialin (Verheijen, F.
      W., Verbeek, E., Aula, N., Beerens, C. E., Havelaar, A. C., Joosse, M., Peltonen,
      L., Aula, P., Galjaard, H., van der Spek, P. J., and Mancini, G. M. (1999) Nat.
      Genet. 23, 462-465; Aula, N., Salomaki, P., Timonen, R., Verheijen, F., Mancini,
      G., Mansson, J. E., Aula, P., and Peltonen, L. (2000) Am. J. Hum. Genet. 67, 832
      840). From the biochemical phenotype of the diseases and the predicted polytopic
      structure of the protein, it has been suggested that sialin functions as a
      lysosomal sialic acid transporter. Here we directly demonstrate that this
      activity is mediated by sialin and that the recombinant protein has functional
      characteristics similar to the native lysosomal sialic acid transport system.
      Furthermore, we describe the effect of disease-causing mutations on the protein.
      We find that the majority of the mutations are associated with a complete loss of
      activity, while the mutations associated with the milder forms of the disease
      lead to reduced, but residual, function. Thus, there is a direct correlation
      between sialin function and the disease state. In addition, we find with one
      mutation that the protein is retained in the endoplasmic reticulum, indicating
      that altered trafficking of sialin is also associated with disease. This analysis
      of the molecular mechanism of sialic acid storage disorders is a further step in
      identifying therapeutic approaches to these diseases.

PMID- 15516338
TI  - 67-kDa laminin receptor promotes internalization of cytotoxic necrotizing factor
      1-expressing Escherichia coli K1 into human brain microvascular endothelial
      cells.
AB  - Escherichia coli K1 is the most common Gram-negative organism causing meningitis,
      and its invasion of human brain microvascular endothelial cells (HBMEC) is a
      prerequisite for penetration into the central nervous system. We have reported
      previously that cytotoxic necrotizing factor 1 (CNF1) contributes to E. coli K1
      invasion of HBMEC and interacts with 37-kDa laminin receptor precursor (37LRP) of
      HBMEC, which is a precursor of 67-kDa laminin receptor (67LR). In the present
      study, we examined the role of 67LR in the CNF1-expressing E. coli K1 invasion of
      HBMEC. Immunofluorescence microscopy and ligand overlay assays showed that 67LR
      is present on the HBMEC membrane and interacts with CNF1 protein as well as the
      CDPGYIGSR laminin peptide. 67LR was up-regulated and clustered at the sites of E.
      coli K1 on HBMEC in a CNF1-dependent manner. Pretreatment of CNF1+ E. coli K1
      with recombinant 37-kDa laminin receptor precursor reduced the invasion rate to
      the level of Deltacnf1 mutant, and the invasion rate of CNF1+ E. coli K1 was
      enhanced in 67LR-overexpressing HBMEC, indicating 67LR is involved in the CNF1+
      E. coli K1 invasion of HBMEC. Coimmunoprecipitation analysis showed that, upon
      incubation with CNF1+ E. coli K1 but not with Deltacnf1 mutant, focal adhesion
      kinase and paxillin were recruited and associated with 67LR. When immobilized
      onto polystyrene beads, CNF1 was sufficient to induce internalization of coupled
      beads into HBMEC through interaction with 67LR. Taken together, this is the first
      demonstration that E. coli K1 invasion of HBMEC occurs through the ligand
      receptor (CNF1-67LR) interaction, and 67LR promotes CNF1-expressing E. coli K1
      internalization of HBMEC.

PMID- 15516339
TI  - cis-acting, element-specific transcriptional activity of differentially
      phosphorylated nuclear factor-kappa B.
AB  - Phosphorylation of nuclear factor-kappa B (NF-kappa B) subunits emerges as a
      mechanism by which transcriptional activity of nuclear NF-kappa B complexes is
      regulated in an inhibitor kappa B-independent fashion. As the main
      transactivator, the p65 subunit of NF-kappa B has an outstanding position in the
      hierarchy of NF-kappa B proteins. p65 is a multiply phosphorylated protein with
      phosphorylation sites in the C-terminal transactivation domain and the N-terminal
      Rel homology domain (RHD). In this study, we describe two previously non-reported
      phospho-acceptor sites within the p65 RHD. We show that differential
      phosphorylation of serine residues within the RHD modulates transcriptional
      activity in a cis-acting element and promoter-specific context, thus leading to a
      phosphorylation state-dependent gene expression profile. RelA(-/-) mouse
      embryonic fibroblasts reconstituted with wild-type p65 or p65 phosphorylation
      deficient mutants showed a distinctive expression profile of synthetic kappa B
      dependent reporters as well as endogenous genes. Hypophosphorylated p65 did not
      display cis-acting element-specific changes in DNA binding or dimerization
      behavior. This study shows for the first time that site-specific phosphorylation
      can target a transcription factor to a particular subset of genes.

PMID- 15516341
TI  - Determination of selectivity and efficacy of fatty acid synthesis inhibitors.
AB  - Type II fatty acid synthesis (FASII) is essential to bacterial cell viability and
      is a promising target for the development of novel antibiotics. In the past
      decade, a few inhibitors have been identified for this pathway, but none of them
      lend themselves to drug development. To find better inhibitors that are potential
      drug candidates, we developed a high throughput assay that identifies inhibitors
      simultaneously against multiple targets within the FASII pathway of most
      bacterial pathogens. We demonstrated that the inverse t(1/2) value of the FASII
      enzyme-catalyzed reaction gives a measure of FASII activity. The Km values of
      octanoyl-CoA and lauroyl-CoA were determined to be 1.1 +/- 0.3 and 10 +/- 2.7
      microM in Staphylococcus aureus and Bacillus subtilis, respectively. The effects
      of free metals and reducing agents on enzyme activity showed an inhibition
      hierarchy of Zn2+ > Ca2+ > Mn2+ > Mg2+; no inhibition was found with beta
      mercaptoethanol or dithiothreitol. We used this assay to screen the natural
      product libraries and isolated an inhibitor, bischloroanthrabenzoxocinone (BABX)
      with a new structure. BABX showed IC50 values of 11.4 and 35.3 microg/ml in the
      S. aureus and Escherichia coli FASII assays, respectively, and good antibacterial
      activities against S. aureus and permeable E. coli strains with minimum
      inhibitory concentrations ranging from 0.2 to 0.4 microg/ml. Furthermore, the
      effectiveness, selectivity, and the in vitro and in vivo correlations of BABX as
      well as other fatty acid inhibitors were elucidated, which will aid in future
      drug discovery.

PMID- 15516340
TI  - Transcript profiling in Arabidopsis reveals complex responses to global
      inhibition of DNA methylation and histone deacetylation.
AB  - Blocking histone deacetylation with trichostatin A (TSA) or blocking cytosine
      methylation using 5-aza-2'-deoxycytosine (aza-dC) can derepress silenced genes in
      multicellular eukaryotes, including animals and plants. We questioned whether DNA
      methylation and histone deacetylation overlap in the regulation of endogenous
      plant genes by monitoring changes in expression of approximately 7800 Arabidopsis
      thaliana genes following treatment with azadC, TSA, or both chemicals together.
      RNA levels for approximately 4% of the genes were reproducibly changed 3-fold or
      more by at least one treatment. Distinct subsets of genes are up-regulated or
      down-regulated in response to aza-dC, TSA, or simultaneous treatment with both
      chemicals, with little overlap among subsets. Surprisingly, the microarray data
      indicate that TSA and aza-dC are often antagonistic rather than synergistic in
      their effects. Analysis of green fluorescent protein transgenic plants confirmed
      this finding, showing that TSA can block the up-regulation of silenced green
      fluorescent protein transgenes in response to aza-dC or a ddm1 (decrease in DNA
      methylation 1) mutation. Our results indicate that global inhibition of DNA
      methylation or histone deacetylation has complex, nonredundant effects for the
      majority of responsive genes and suggest that activation of some genes requires
      one or more TSA-sensitive deacetylation events in addition to cytosine
      demethylation.

PMID- 15516342
TI  - Engaged and bystander T cell receptors are down-modulated by different
      endocytotic pathways.
AB  - T cell antigen receptor (TCR) engagement by stimulatory antibodies or its major
      histocompatibility complex-antigen ligand results in its down-modulation from the
      cell surface, a phenomenon that is thought to play a role in T cell
      desensitization. However, TCR engagement results in the down-modulation not only
      of the engaged receptors but also of non-engaged bystander TCRs. We have
      investigated the mechanisms that mediate the down-modulation of engaged and
      bystander receptors and show that co-modulation of the bystander TCRs requires
      protein-tyrosine kinase activity and is mediated by clathrin-coated pits. In
      contrast, the down-modulation of engaged TCRs is independent of protein-tyrosine
      kinases and clathrin pits, suggesting that this process is mediated by an
      alternate mechanism. Indeed, down-modulation of engaged TCRs appears to depend
      upon lipid rafts, because cholesterol depletion with methyl-beta-cyclodextrin
      completely blocks this process. Thus, two independent pathways of internalization
      are involved in TCR down-modulation and act differentially on directly engaged
      and bystander receptors. Finally, we propose that although both mechanisms
      coexist, the predominance of one or the other mechanisms will depend on the dose
      of ligand.

PMID- 15516343
TI  - UK legislation on analgesic packs: before and after study of long term effect on
      poisonings.
AB  - OBJECTIVE: To evaluate the long term effect of legislation limiting the size of
      packs of analgesics sold over the counter. DESIGN: Before and after study.
      SETTING: Suicides in England and Wales, data from six liver units in England and
      Scotland and five general hospitals in England, and UK data on sales of
      analgesics, between September 1993 and September 2002. DATA SOURCES: Office for
      National Statistics; six liver units in England and Scotland; monitoring systems
      in general hospitals in Oxford, Manchester, and Derby; and Intercontinental
      Medical Statistics Health UK. MAIN OUTCOME MEASURES: Deaths by suicidal overdose
      with paracetamol, salicylates, or ibuprofen; numbers of patients admitted to
      liver units, listed for liver transplant, and undergoing transplantations for
      paracetamol induced hepatotoxicity; non-fatal self poisonings with analgesics and
      numbers of tablets taken; and sales figures for analgesics. RESULTS: Suicidal
      deaths from paracetamol and salicylates were reduced by 22% (95% confidence
      interval 11% to 32%) in the year after the change in legislation on 16 September
      1998, and this reduction persisted in the next two years. Liver unit admissions
      and liver transplants for paracetamol induced hepatotoxicity were reduced by
      around 30% in the four years after the legislation. Numbers of paracetamol and
      salicylate tablets in non-fatal overdoses were reduced in the three years after
      the legislation. Large overdoses were reduced by 20% (9% to 29%) for paracetamol
      and by 39% (14% to 57%) for salicylates in the second and third years after the
      legislation. Ibuprofen overdoses increased after the legislation, but with little
      or no effect on deaths. CONCLUSION: Legislation restricting pack sizes of
      analgesics in the United Kingdom has been beneficial. A further reduction in pack
      sizes could prevent more deaths.

PMID- 15516344
TI  - Comparative analysis of passive dosimetry and biomonitoring for assessing
      chlorpyrifos exposure in pesticide workers.
AB  - Under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), the US
      Environmental Protection Agency (EPA) has the authority to regulate the use of
      pesticides to prevent unreasonable adverse human health effects associated with
      pesticide exposure. Accordingly, the EPA requires pesticide registrants to
      perform studies evaluating the potential for pesticide handler exposure. Data
      from five such studies that included exposure measurements based on both external
      measurements and biological monitoring were used to examine methods of
      assessment, routes and determinants of exposure and dose to the pesticide
      chlorpyrifos. Eighty workers across four job classes were included: mixer/loaders
      (M/L, n = 24), mixer/loader/applicators (M/L/A, n = 37), applicators (A, n = 9)
      and re-entry scouts (RS, n = 10). Results showed that doses were highly variable
      and differed by job class (P < 0.05) with median total (inhalation and dermal
      combined) exposure-derived absorbed doses (EDADtot) of 129, 88, 85 and 45
      microg/application for A, M/L/A, M/L and RS, respectively. Doses derived from the
      measurement of 3,5,6-trichloro- 2-pyridinol (3,5,6-TCP) in urine were similar in
      magnitude but differed in rank with median values of 275, 189, 122 and 97
      microg/application for A, M/L, RS, and M/L/A, respectively. The relative
      contribution of dermal to inhalation exposure was examined by their ratio. The
      median ratios of exposure-derived absorbed dermal dose (EDADderm) (assuming 3%
      absorption) to exposure-derived absorbed inhalation dose (EDADinh) (assuming 100%
      absorption) across job classes were 1.7, 1.5, 0.44 and 0.18 for RS, M/L, A and
      M/L/A, respectively, with an overall median of 0.6. For 34 of 77 workers (44%),
      this ratio exceeded 1.0, indicating the significance of the dermal exposure
      pathway. Different dermal absorption factor (DAF) assumptions were examined by
      comparing EDADtot to the biomarker-derived absorbed dose (BDAD) as a ratio where
      EDADtot was calculated assuming a DAF of 1, 3 and 10%. Median ratios of 0.45,
      0.71 and 1.28, respectively, were determined suggesting the DAF is within the
      range of 3-10%. A simple linear regression of urinary 3,5,6-TCP against EDADtot
      indicates a positive association explaining 29% of the variability in the 3,5,6
      TCP derived estimate of dose. A multiple linear regression model including the
      variables EDADderm, EDADinh and application type explained 46% of the variability
      (R2 = 0.46) in the urinary dose estimate. EDADderm was marginally significant (P
      = 0.066) while EDADinh was not (P = 0.57). The EDADderm regression coefficient
      (0.0007) exceeded the coefficient for EDADinh (0.00002) by a factor of 35. This
      study demonstrates the value of the pesticide registrant database for the purpose
      of evaluating pesticide worker exposure. It highlights the significance of the
      dermal exposure pathway, and identifies the need for methods and research to
      close the gap between external and internal exposure measures.

PMID- 15516345
TI  - Minimum effective local anaesthetic dose of isobaric levobupivacaine and
      ropivacaine administered via a spinal catheter for hip replacement surgery.
AB  - BACKGROUND: Continuous spinal anaesthesia with spinal catheters allows
      incremental dosing of local anaesthetic and, consequently, less haemodynamic
      changes. However, little is known about the required doses. Therefore, we
      designed a study to assess the minimum effective local anaesthetic dose (MLAD) of
      levobupivacaine and ropivacaine in this context. METHODS: Forty-one patients
      undergoing hip replacement surgery were randomly allocated to one of the two
      local anaesthetic groups in a double-blind manner. The initial dose of local
      anaesthetic was determined by the response of the previous patient: the effective
      dose resulted in a 1 mg decrease in the dose of levobupivacaine or ropivacaine,
      and an ineffective dose resulted in a 1 mg increase. The MLAD was calculated by
      the Dixon up-and-down method. RESULTS: The MLAD of levobupivacaine was 11.7 mg
      (95% CI, 11.1-12.4) and that of ropivacaine 12.8 mg (95% CI, 12.2-13.4).
      CONCLUSIONS: These doses are significantly smaller than doses reported before for
      single-shot spinal anaesthesia. Continuous spinal anaesthesia allows the use of
      relatively small doses of local anaesthetic.

PMID- 15516346
TI  - Gut permeability in paediatric cardiac surgery.
AB  - BACKGROUND: Intestinal mucosal ischaemia can occur in infants and children during
      and after cardiac surgery. Severe decreases in mucosal perfusion may cause
      complications such as necrotizing enterocolitis and postoperative mortality. We
      investigated gut permeability in paediatric patients undergoing cardiac surgery
      using the dual sugar permeability test and absorption of two other saccharides.
      METHODS: Thirty-four patients undergoing palliative or corrective surgical
      procedures with and without cardiopulmonary bypass were investigated. Intestinal
      permeability was measured using 3-O-methyl-D-glucose, D-xylose, L-rhamnose and
      lactulose, given orally after induction of anaesthesia and 12 and 24 h later.
      RESULTS: Lactulose/rhamnose ratios were raised from the outset [median 0.39
      (confidence interval 0.07-1.8 for patients undergoing operations without
      cardiopulmonary bypass and 0.30 (0.02-2.6) with cardiopulmonary bypass]. The
      highest lactulose/rhamnose ratios were recorded 12 h after surgery 0.32 (0.07
      6.9), when cardiopulmonary bypass was used. This is approximately seven times the
      value expected in healthy children. There was an improvement in patients not
      undergoing cardiopulmonary bypass: 0.22 (0.03-0.85) 12 h and 0.11 (0-0.48) 24 h
      after induction of anaesthesia. Patients undergoing repair of aortic coarctation
      showed the fastest recovery: 0.09 (0.03-0.31) 12 h and 0.07 (0.04-0.35) 24 h
      after induction of anaesthesia. CONCLUSIONS: Patients with congenital heart
      defects have abnormal gut permeability when compared with healthy children of
      similar age. Cardiopulmonary bypass seems to affect the intestinal barrier
      morphologically (lactulose and rhamnose absorption) and functionally (3-O-methyl
      D-glucose and D-xylose absorption).

PMID- 15516347
TI  - Bispectral index and A-line AAI index as guidance for desflurane-remifentanil
      anaesthesia compared with a standard practice group: a multicentre study.
AB  - BACKGROUND: This study was designed to investigate the impact of bispectral index
      (BIS) or A-line AAI index (based on middle-latency auditory evoked potential)
      monitoring on recovery times and drug consumption when compared with standard
      anaesthetic practice during desflurane-remifentanil anaesthesia. METHODS: After
      having obtained approval from the institutional review board and written informed
      consent, 200 adult patients undergoing minor surgical procedures were randomized
      to receive a desflurane-remifentanil anaesthetic controlled either solely by
      clinical parameters or by BIS or AAI to the following target values: during
      maintenance of anaesthesia to a value of '50' (BIS) or '30' (AAI), 15 min before
      the end of surgery to '60' (BIS) or '45' (AAI). Recovery times and drug
      consumption were recorded by a blinded investigator. RESULTS: Compared with
      standard practice, patients with BIS or AAI monitoring needed similar desflurane
      concentrations (standard practice 2.9 [0.5] vol%, BIS 3.3 [0.9] vol%, AAI 2.6
      [0.5] vol%), and had similar recovery times (open eyes 5.6 [2.5] min, 5.9 [3.4]
      min, 5.0 [3.1] min; extubation 6.3 [2.4] min, 6.6 [3.5] min, 5.6 [3.0] min;
      stating name 7.3 [2.4] min, 7.6 [3.5] min, 7.3 [6.6] min). CONCLUSIONS: Compared
      with standard anaesthetic practice BIS and AAI guided titration to the used
      target ranges did not result in a reduction of desflurane consumption or recovery
      times during minor surgery with use of remifentanil.

PMID- 15516348
TI  - Corticosteroid injections for trochanteric bursitis: is fluoroscopy necessary? A
      pilot study.
AB  - BACKGROUND: Numerous studies have demonstrated that therapeutic injections
      carried out to treat a variety of different pain conditions should ideally be
      performed under radiological guidance because of the propensity for blinded
      injections to be inaccurate. Although trochanteric bursa injections are commonly
      performed to treat hip pain, they have never been described using fluoroscopy.
      METHODS: The authors reviewed recorded data on 40 patients who underwent
      trochanteric bursa injections for hip pain with or without low back pain. The
      initial needle placement was done blindly, with all subsequent attempts done
      using fluoroscopic guidance. After bone contact, imaging was used to determine if
      the needle was positioned on the lateral edge of the greater trochanter (GT).
      Once this occurred, 1 ml of radiopaque contrast was injected to assess bursa
      spread. RESULTS: The GT was contacted in 78% of cases and a bursagram obtained in
      45% of patients on the first needle placement. In 23% of patients a bursagram was
      obtained on the second attempt and in another 23% on the third attempt. Four
      patients (10%) required four or more needle placements before a bursagram was
      appreciated. Attending physicians obtained a bursagram on the first attempt 53%
      of the time vs 46% for fellows and 36% for residents (P=0.64). Older patients
      were more likely to require multiple injections than younger patients.
      CONCLUSIONS: Radiological confirmation of bursal spread is necessary to ensure
      that the injectate reaches the area of pathology during trochanteric bursa
      injections.

PMID- 15516349
TI  - In vitro effects of local anaesthetics on the thromboelastographic profile of
      parturients.
AB  - BACKGROUND: Post-dural puncture headache can be an incapacitating complication of
      obstetric epidural analgesia/anaesthesia and early or prophylactic epidural blood
      patch (EBP) is one of the treatment options. Although local anaesthetic (LA)
      agents have been shown to have anticoagulation effects in vitro, peri-partum
      women are known to be hypercoagulable. We postulated that the presence of
      residual LA might not result in impaired haemostasis of the EBP in parturients.
      METHODS: Blood samples from 10 healthy term parturients were subjected to
      thromboelastography after the addition of four different LA (lidocaine,
      bupivacaine, levobupivacaine, and ropivacaine) preparations. RESULTS: There was a
      significant reduction in reaction (R) and coagulation (K) time (P<0.001, P<0.05)
      and an increase in alpha degrees angle (P<0.01) when comparing undiluted blood
      with the saline control group. Maximum amplitude (MA) and clot lysis (Ly30) did
      not change significantly despite the 50% dilution. The thromboelastographic
      parameters of all four LA-treated groups were no different from their saline
      controls and from each other. CONCLUSION: At clinical dosages, LA did not cause
      any hypocoagulable changes on the thromboelastographic profile of healthy
      parturients.

PMID- 15516350
TI  - Mortality analysis in hip fracture patients: implications for design of future
      outcome trials.
AB  - INTRODUCTION: Patients with hip fractures are usually frail and elderly with a 30
      day mortality in excess of 10% in European series. Perioperative morbidity is
      often multifactorial in nature, and unimodal interventions will not necessarily
      decrease mortality. The purpose of this prospective study was to analyse causes
      of mortality, and thereby the potential and limitations to decrease mortality
      after hip fracture surgery. METHODS: 300 consecutive, unselected hip fracture
      patients were treated in a multimodal rehabilitation programme with continuous
      perioperative epidural analgesia and anaesthesia, early surgery, standardized
      fluid and transfusion therapy, enforced oral nutrition and early mobilization and
      physiotherapy. All deaths within 30 days of surgery or during primary
      hospitalization were analysed and classified according to whether death was
      unavoidable, probably unavoidable, or potentially avoidable. RESULTS: Thirty-day
      mortality was 13.3% (40 patients) and the total perioperative mortality was 15.6%
      (47 patients). Death was definitely unavoidable in 28%, probably unavoidable in
      15%, and in theory potentially avoidable in 57%. In the patients where death was
      potentially avoidable, active care was curtailed in 16 of 27 (59%) patients.
      CONCLUSION: About a quarter of the total mortality in hip fracture patients is
      definitely unavoidable, and death is probably only avoidable in about half of the
      unselected patients. These results have important implications for the design of
      future outcome studies, which should focus on other relevant outcomes than
      mortality per se.

PMID- 15516351
TI  - Clonidine as an adjuvant to local anaesthetic axillary brachial plexus block: a
      randomized, controlled study.
AB  - BACKGROUND: We compared the effects of clonidine added to levobupivacaine and
      bupivacaine on axillary brachial plexus block as well as the effectiveness of
      levobupivacaine alone compared with bupivacaine alone. METHODS: In this
      prospective, randomized, controlled, double-blind trial, four groups of 20
      patients each were investigated, using (i) 40 ml of levobupivacaine 0.5% plus
      0.150 mg of clonidine, (ii) 40 ml of levobupivacaine 0.5% plus 1 ml of NaCl 0.9%,
      (iii) 40 ml of bupivacaine 0.5% plus 0.150 mg of clonidine, and (iv) 40 ml of
      bupivacaine 0.5% plus 1 ml of NaCl 0.9%, respectively. The onset of motor and
      sensory block and duration of sensory block were recorded. RESULTS: There was no
      significant difference in duration between groups, but a significantly higher
      variance (P<0.001) was found in the two groups with clonidine than in the two
      groups without. CONCLUSIONS: These findings suggest responder and non-responder
      behaviour is a result of the addition of clonidine.

PMID- 15516352
TI  - Comparison of plain and hyperbaric solutions of ropivacaine for spinal
      anaesthesia.
AB  - BACKGROUND: Preliminary work has shown that ropivacaine provides spinal
      anaesthesia of shorter duration than bupivacaine, and may be of particular use in
      the day-case setting. However, there are few data comparing the actions of plain
      and hyperbaric solutions of this drug. METHODS: Forty ASA grade I-II patients
      undergoing elective perineal surgery under spinal anaesthesia were randomized to
      receive 3 ml ropivacaine 5 mg ml(-1), either in plain solution or with glucose 50
      mg ml(-1). The extent and duration of sensory and motor block, pulse rate, blood
      pressure, and time to mobilization were recorded. RESULTS: Two patients (one per
      group) were withdrawn because of total block failure. There were significant
      differences in median time to onset of sensory block at T10 (plain 10 min;
      hyperbaric 5 min; P<0.01), median maximum extent (plain T8; hyperbaric T4;
      P<0.05), and median duration of sensory block at T10 (plain 25 min; hyperbaric
      115 min; P<0.001). However, median times to complete regression of both sensory
      (270 vs 240 min; P<0.05) and motor (180 vs 120 min; P<0.001) block were longer in
      the plain group. Patients therefore mobilized sooner in the hyperbaric group (218
      [n=16] vs 286 min [n=17]; P<0.01). All the hyperbaric blocks were adequate for
      surgery, but three patients receiving plain ropivacaine required general
      anaesthesia. CONCLUSION: Addition of glucose 50 mg ml(-1) to ropivacaine 5 mg ml(
      1) increases the speed of onset, block reliability, duration of useful block for
      perineal surgery, and speed of recovery. Plain solutions are less reliable for
      surgery above a dermatomal level of L1.

PMID- 15516353
TI  - Pharmacokinetics of controlled release morphine (MST) in patients with liver
      carcinoma.
AB  - BACKGROUND: There are no studies reported on the pharmacokinetics of controlled
      release morphine (MST) in patients with hepatocellular carcinoma, the fifth most
      common cancer in the world. METHODS: We have studied the pharmacokinetic profile
      of MST (30 mg) in 15 patients with liver carcinoma (eight with primary carcinoma
      on top of chronic hepatitis C, and seven with secondary metastatic liver
      malignancy as a result of other primary) compared with our previously published
      data for 10 healthy controls. Plasma morphine concentrations were measured in
      venous blood samples at intervals up to 12 h by high-pressure liquid
      chromatography. Total body clearance (Cl) and systemic bioavailability were
      estimated using a compartmental method. RESULTS: Morphine bioavailability showed
      a substantial increase in patients with primary liver and secondary metastatic
      carcinoma than that of controls (64.8, 62.1, and 16.8%, respectively). The area
      under the serum concentration-time curve increased 4-fold in primary carcinoma
      (416 [sem25] microg h(-1) litre(-1)) and 3-fold (303 [21] microg h(-1) litre(-1))
      in metastatic liver patients compared with healthy control (92.5 [3] microg h(-1)
      litre(-1)). No significant difference was found in T(max) between the two
      malignant groups but C(max) was significantly greater in primary liver carcinoma
      patients. Impaired morphine elimination was noted in primary carcinoma only
      (t(1/2) 5.99 [0.39] h). CONCLUSION: Careful administration of morphine is
      recommended in patients with liver cancer.

PMID- 15516354
TI  - Tracheal intubation without the use of neuromuscular blocking agents.

PMID- 15516355
TI  - Trends in monitoring patients with aneurysmal subarachnoid haemorrhage.
AB  - After aneurysmal subarachnoid haemorrhage (SAH), the clinical outcome depends
      upon the primary haemorrhage and a number of secondary insults in the acute post
      haemorrhagic period. Some secondary insults are potentially preventable but
      prevention requires prompt recognition of cerebral or systemic complications.
      Currently, several neuro-monitoring techniques are available; this review
      describes the most frequently used techniques and discusses indications for their
      use, and their value in diagnosis and prognosis. None of the techniques, when
      considered in isolation, has proved sufficient after SAH. Furthermore, the use of
      multi-modality monitoring is hampered by a lack of clinical studies that identify
      combinations of specific techniques in terms of clinical information and
      reliability. However, ischaemia at the tissue level can be detected by
      intracerebral microdialysis technique. Used together with the conventional
      monitoring systems, for example intracranial pressure measurements, transcranial
      Doppler ultrasound and modern neuro-imaging, direct assessment of biochemical
      markers by intracerebral microdialysis is promising in the advancement of
      neurointensive care of patients with SAH. A successfully implemented monitoring
      system provides answers but it also raises valuable new questions challenging our
      current understanding of the brain injury after SAH.

PMID- 15516356
TI  - Effects of isoflurane and propofol on cortical somatosensory evoked potentials
      during comparable depth of anaesthesia as guided by bispectral index.
AB  - BACKGROUND: The aim of this study was to determine if propofol caused less
      suppression of cortical somatosensory evoked potentials (SSEPs) during spine
      surgery compared with isoflurane during comparable depth of anaesthesia as guided
      by bispectral index (BIS) measurements. METHODS: This was a randomized controlled
      trial of propofol and isoflurane involving 60 patients undergoing elective spine
      surgery. BIS monitoring was used to guide a consistent and comparable depth of
      anaesthesia, the index was maintained at between 40 and 50 during anaesthesia.
      The cortical SSEP P40-N50 peak-to-peak amplitude and latency time to the P40 peak
      were measured before induction of anaesthesia, after induction of anaesthesia, at
      the start of skin incision, at the start of pedicle screw insertion and at the
      start of rod insertion, by a neurophysiologist blinded to drug allocation.
      RESULTS: Both propofol and isoflurane decreased SSEP amplitude and increased
      latency during the course of anaesthesia. After achieving a comparable depth of
      anaesthesia, the SSEP amplitude was significantly lower with isoflurane, 1.5
      (1.0) vs 2.4 (1.4) muV (P=0.005). Latency was significantly longer with
      isoflurane, 39.5 (3.9) vs 37.3 (3.1) ms (P=0.024). Isoflurane was associated with
      greater variability of SSEP amplitude during the course of anaesthesia and
      surgery, coefficient of variation 35.4 (18.0) vs 21.2 (10.2)% (P=0.008).
      CONCLUSIONS: Propofol anaesthesia caused less suppression of the cortical SSEP,
      with better preservation of SSEP amplitude, and less variability at an equivalent
      depth of anaesthesia.

PMID- 15516357
TI  - Burns and tracheo-oesophageal-cutaneous fistula.
AB  - We report an unusual case of electric burns suffered by a 15-yr-old boy. The
      patient's neck had come in contact with a high voltage broken electric wire and
      by reflex he had pulled it away with his right hand. He presented with a tracheo
      cutaneous fistula with a right-sided pneumothorax. Emergency airway management
      included insertion of a tracheostomy tube through the traumatic opening in the
      neck and insertion of an intercostal tube drain. When the diagnostic endoscopy
      revealed an externally communicating tracheo-oesophageal fistula, protecting the
      lower airways from gastrointestinal contamination became a priority. The patient
      was anaesthetized through the traumatic tracheostomy and a formal low
      tracheostomy was done below the level of the fistula. The patient then underwent
      oesophageal reconstruction with a stomach free flap. Tracheo-oesophageal
      cutaneous fistula is a rare presentation of electric burns. The anaesthetic
      management of the emergency difficult airway in any penetrating neck injury can
      be extremely difficult requiring a carefully planned multi-disciplinary approach.

PMID- 15516358
TI  - Membrane and cortical abnormalities in post-ovulatory aged eggs: analysis of
      fertilizability and establishment of the membrane block to polyspermy.
AB  - Fertilization at increased times after ovulation is associated with poor
      reproductive outcomes. This study examines the effects of post-ovulatory ageing
      on egg membrane function through analyses of mouse eggs collected at 13 and 22 h
      post-HCG ('young' and 'aged' eggs, respectively). Experiments in which fertilized
      zona pellucida-free young and aged eggs are challenged with additional sperm
      reveal that aged eggs are less able to establish a membrane block to prevent
      polyspermy, since sperm penetrate 24% of fertilized aged eggs but are unable to
      penetrate fertilized young eggs. This is not due to a failure of aged eggs to
      respond to fertilization, as the extent of sperm-induced cortical granule
      exocytosis is similar in aged and young eggs. Post-ovulatory ageing also affects
      egg membrane receptivity to sperm as a subset of zona pellucida-free aged eggs
      are slow to fertilize or resistant to fertilization. Sperm binding to young and
      aged eggs is similar, but aged eggs develop cytoskeletal abnormalities that may
      affect membrane/cortical function, such as the ability of the egg membrane to
      support sperm-egg fusion. These data demonstrate that the poor reproductive
      outcomes associated with post-ovulatory ageing could be a result of reduced
      fertilization, due to reduced egg membrane receptivity to sperm, or a result of
      increased incidence of polyspermy, due to the reduced ability to establish a
      membrane block to polyspermy. This analysis of egg membrane function deficiencies
      provides insights into post-ovulatory ageing and has implications for assisted
      reproductive technologies.

PMID- 15516359
TI  - Analysis of the participation of N-acetylglucosamine in the different steps of
      sperm-zona pellucida interaction in hamster.
AB  - Glycoproteins and lectin-like proteins mediate sperm-zona pellucida interaction.
      The present study analysed the participation of carbohydrates in the different
      stages of sperm interaction with the zona pellucida in hamster, by determining
      the effects of different monosaccharides. N-acetylglucosamine (GlcNAc, 1 mM)
      reduced sperm ability to bind to the zona pellucida. Surprisingly, spontaneous
      acrosome reaction (AR) was also inhibited by this sugar. In order to analyse the
      effect of GlcNAc on sperm-zona pellucida binding, independent of its effect on
      the AR, strontium (Sr) was used as a calcium (Ca) replacement in the sperm
      capacitation and co-incubation medium. Sr seemed to be able to replace Ca for
      sperm capacitation, at least when measured as the ability to bind to the zona
      pellucida, and undergo AR when Ca is provided. Moreover, sperm-zona pellucida
      binding could also take place in a Sr-modified medium. When binding assays were
      carried out in the Sr medium, GlcNAc also produced an inhibitory effect. This
      could be reproduced when sperm, but not oocytes, were pre-incubated with the
      monosaccharide. IVF assays were also carried out to analyse the participation of
      GlcNAc in the different steps of sperm-oocyte interaction. Taken together, the
      results support the involvement of the GlcNAc residues of the zona pellucida in
      the early steps of the interaction with sperm.

PMID- 15516360
TI  - Polymorphisms of genes involved in innate immunity: association with preterm
      delivery.
AB  - An altered inflammatory activity due to functionally relevant polymorphisms of
      the innate immune system may influence pathways leading to labour and, therefore,
      impact on the frequency of preterm birth. We examined five polymorphisms of the
      innate immune system in a large cohort of preterm very-low-birth-weight (VLBW, n
      = 909) and term-born infants (n = 491) and their mothers (n = 747). The primary
      outcome was preterm versus term birth. Frequencies of polymorphisms in mothers of
      term-born infants versus mothers of VLBW infants and term infants versus preterm
      VLBW infants (singletons) are given. Homozygous CD14-159T: 18.5 versus 21.8%
      (mothers) and 19.6 versus 21.2% (infants). Homozygous interleukin IL-6-174G: 28.8
      versus 38% (P = 0.018, mothers) and 30 versus 32.7% (infants). Homozygous or
      heterozygous nuclear oligomerization domain NOD2-3020insC: 6.9 versus 6.1%
      (mothers) and 5.7 versus 5.1% (infants). Heterozygous or homozygous toll-like
      receptor TLR2-Arg753Gln: 6.9 versus 6.1% (mothers) and 5.7 versus 5.1% (infants).
      Homozygous or heterozygous TLR4-896G: 8.1 versus 11.5% (mothers) and 11.6 versus
      10.5% (infants). Although the homozygous maternal IL-6-174G genotype was found to
      be independently associated with preterm delivery in multivariate regression
      analysis, the incidence of intrauterine infection was not significantly increased
      in mothers of preterm VLBW-infants, carrying this or other polymorphisms of the
      innate immune system. The overall influence of the investigated polymorphisms on
      the development of preterm delivery seems moderate, since only the maternal IL6
      174G genotype was associated with preterm birth and none of the polymorphisms
      were associated with intrauterine infection as the cause of preterm birth.

PMID- 15516361
TI  - Directed molecular evolution by somatic hypermutation.
AB  - After rearrangement of immunoglobulin gene segments, the immune system evolves
      the antibody repertoire by mutating the immunoglobulin variable region at a high
      rate. While this somatic hypermutation was thought to occur only at the variable
      region, recent studies suggest that hypermutation can occur at locations
      throughout the genome. Building upon this notion, we sought to exploit this
      mechanism as a mutagenesis tool. We created a substrate based on GFP that could
      be screened using flow cytometry and showed that retroviral infection can deliver
      the transgene to genomic locations that support hypermutation. Infected cells
      generated various GFP mutants with increased fluorescence intensity and analysis
      revealed mutations not only at the chromophore, but also an unexpected mutation
      at a distant residue. Our results demonstrate in principle that immunoglobulin
      somatic hypermutation can be a potent means of mutagenesis. With appropriate
      selection conditions it may be utilized to evolve gene products with desired
      properties.

PMID- 15516362
TI  - Is carbon monoxide-mediated cyclic guanosine monophosphate production responsible
      for low blood pressure in neonatal respiratory distress syndrome?
AB  - Infant respiratory distress syndrome (RDS) involves inflammatory processes,
      causing an increased expression of inducible heme oxygenase with subsequent
      production of carbon monoxide (CO). We hypothesized that increased production of
      CO during RDS might be responsible for increased plasma levels of vasodilatory
      cGMP and, consequently, low blood pressure observed in infants with RDS. Fifty
      two infants (no-RDS, n = 21; RDS, n = 31), consecutively admitted to the neonatal
      intensive care unit (NICU) between January and October 2003 were included.
      Hemoglobin-bound carbon monoxide (COHb), plasma cGMP, plasma nitric oxide (NOx),
      and bilirubin were determined at 0-12, 48-72, and at 168 h postnatally, with
      simultaneous registration of arterial blood pressure. Infants with RDS had higher
      levels of cGMP and COHb compared with no-RDS infants (RDS vs. no-RDS: cGMP
      ranging from 76 to 101 vs. 58 to 82 nmol/l; COHb ranging from 1.2 to 1.4 vs. 0.9
      to 1.0%). Highest values were reached at 48-72 h [RDS vs. no-RDS mean (SD): cGMP
      100 (39) vs. 82 (25) nmol/l (P < 0.001); COHb 1.38 (0.46) vs. 0.91 (0.26)% (P <
      0.0001)]. Arterial blood pressure was lower and more blood pressure support was
      needed in RDS infants at that point of time [RDS vs. no-RDS mean (SD): mean
      arterial blood pressure 33 (6) vs. 42 (5) mmHg (P < 0.05)]. NOx was not different
      between groups and did not vary with time. Multiple linear regression analysis
      showed a significant correlation between cGMP and COHb, suggesting a causal
      relationship. Mean arterial blood pressure appeared to be primarily correlated to
      cGMP levels (P < 0.001). We conclude that a CO-mediated increase in cGMP causes
      systemic vasodilation with a consequent lower blood pressure and increased need
      for blood pressure support in preterm infants with RDS.

PMID- 15516363
TI  - Determinants of coronary blood flow in humans: quantification by intracoronary
      Doppler and ultrasound.
AB  - The direct determinants of coronary flow are lumen area and blood flow velocity;
      however, the precise mechanisms that control these factors are not fully
      understood. The aim of the present study was to assess by which mechanisms lumen
      area and coronary flow velocity interact with hemodynamic and morphometric
      factors, thereby influencing coronary flow. Intracoronary Doppler and ultrasound
      measurements were performed in 28 patients without coronary lumen irregularities.
      Flow velocity and lumen cross-sectional area were measured in the proximal
      segments of all three coronary arteries. Global lumen cross-sectional area and
      global flow were obtained by adding up the values of all three coronary arteries.
      Left ventricular mass was assessed by echocardiography. Stress-mass-heart rate
      and pressure-rate products reflecting myocardial oxygen demand were calculated.
      Global coronary flow increased during adenosine-induced hyperemia from 197 +/- 72
      to 637 +/- 204 ml/min (P < 0.001). Global coronary flow closely correlated with
      the stress-mass-heart rate product (r = 0.62; P < 0.001). Looking at the two
      constituents of flow separately, global coronary cross-sectional area was closely
      related to left ventricular muscle mass (r = 0.61; P < 0.001), whereas mean
      coronary flow velocity at rest showed a strong linear relation with the pressure
      rate product (r = 0.64; P < 0.001). There was no interaction between cross
      sectional area and blood flow velocity in any of the coronary vessels. Coronary
      lumen size and flow velocity, the two determinants of coronary flow, are
      principally determined by different physiological factors. Long-term flow
      adaptation is achieved by an increase in coronary lumen size, whereas short-term
      myocardial oxygen requirements are met by changes in resting flow velocity.

PMID- 15516364
TI  - AMP kinase expression and activity in human skeletal muscle: effects of
      immobilization, retraining, and creatine supplementation.
AB  - The effects of leg immobilization and retraining in combination with oral
      creatine intake on muscle AMP-activated protein kinase (AMPK) protein expression
      and phosphorylation status were investigated. A double-blind trial was performed
      in young healthy volunteers (n = 22). A cast immobilized the right leg for 2 wk,
      whereafter the knee-extensor muscles of that leg were retrained for 6 wk. Half of
      the subjects received creatine monohydrate throughout the study (Cr; from 15 g
      down to 2.5 g daily), and the others ingested placebo (P; maltodextrin). Before
      and after immobilization and retraining, needle biopsies were taken from the
      right and left vastus lateralis muscles. In the right leg of P and Cr,
      immobilization did not affect AMPK alpha1-, alpha2-, and beta2-subunit expression
      or AMPK alpha-subunit phosphorylation status. However, irrespective of the
      treatment received, retraining increased the degree of alpha-subunit
      phosphorylation by approximately 25% (P <0.05) and increased AMPK alpha1-subunit
      expression (P <0.05) in both groups. From the start to the end of the study, AMPK
      subunit protein expression and alpha-subunit phosphorylation status were
      unchanged in the contralateral control leg. It is concluded that immobilization
      induced muscle inactivity for 2 wk does not alter AMPK alpha1-, alpha2-, and
      beta2-subunit expression or alpha-AMPK phosphorylation status. Furthermore, the
      present observations indicate that AMPK probably is not implicated in the
      previously reported beneficial effects of oral creatine supplementation on muscle
      during immobilization and rehabilitative weight training.

PMID- 15516365
TI  - Hypoxic pulmonary hypertension is prevented in rats with common bile duct
      ligation.
AB  - Biliary cirrhosis in the rat triggers intrapulmonary vasodilatation and gas
      exchange abnormalities that characterize the hepatopulmonary syndrome. This
      vasodilatation correlates with increased levels of pulmonary microcirculatory
      endothelial NO synthase (eNOS) and hepatic and plasma endothelin-1 (ET-1).
      Importantly, during cirrhosis, the pulmonary vascular responses to acute hypoxia
      are blunted. The purpose of this work was to examine the pulmonary vascular
      responses and adaptations to the combination of liver cirrhosis and chronic
      hypoxia (CH). In addition to hemodynamic measurements, we investigated whether
      pulmonary expression changes of eNOS, ET-1 and its receptors (endothelin A and
      B), or heme oxygenase 1 in experimental cirrhosis affect the development of
      hypoxic pulmonary hypertension. We induced cirrhosis in male Sprague-Dawley rats
      using common bile duct ligation (CBDL) and exposed them to CH (inspired PO2
      approximately 76 Torr) or maintained them in Denver (Den, inspired PO2
      approximately 122 Torr) for 3 wk. Our data show 1) CBDL-CH rats had a persistent
      blunted hypoxic pulmonary vasoconstriction similar to CBDL-Den; 2) the
      development of hypoxic pulmonary hypertension was completely prevented in the
      CBDL-CH rats, as indicated by normal pulmonary arterial pressure and lack of
      right ventricular hypertrophy and pulmonary arteriole remodeling; and 3)
      selective increases in expression of ET-1, pulmonary endothelin B receptor, eNOS,
      and heme oxygenase 1 are potential mechanisms of protection against hypoxic
      pulmonary hypertension in the CBDL-CH rats. These data demonstrate that unique
      and undefined hepatic-pulmonary interactions occur during liver cirrhosis and
      chronic hypoxia. Understanding these interactions may provide important
      information for the prevention and treatment of pulmonary hypertension.

PMID- 15516366
TI  - Vascular growth and remodeling in compensatory lung growth following right
      lobectomy.
AB  - Studies in animal models have shown that, following lobectomy (LBX), there is
      compensatory growth in the remaining lung. The vascular growth response following
      right LBX (R-LBX) is poorly understood. To test the hypothesis that arterial
      growth and remodeling occur in response to LBX, in proportion to the amount of
      right lung tissue removed, two (24% of lung mass; R-LBX2 group) or three right
      lobes (52% of lung mass; R-LBX3 group) were removed via thoracotomy from adult
      rats. Sham control animals underwent thoracotomy only. Arteriograms were
      generated 3 wk after surgery. The areas of the left lung arteriogram, arterial
      branching, length of arterial branches, arterial density, and arterial-to
      alveolar ratios were measured. To determine whether R-LBX causes vascular
      remodeling and pulmonary hypertension, muscularization of arterioles and right
      ventricular hypertrophy were assessed. Lung weight and volume indexes were
      greater in R-LBX3. Arterial area of the left lung increased 26% in R-LBX2 and 47%
      in R-LBX3. The length of large arteries increased in R-LBX3 and to a lesser
      extent in R-LBX2. The ratio of distal pulmonary arteries to alveoli was similar
      after R-LBX2 compared with sham but was 30% lower in R-LBX3. Muscularization of
      arterioles increased after R-LBX3, but not in R-LBX2. Right ventricular
      hypertrophy increased 50-70% in R-LBX3, but not in R-LBX2. Whereas removal of
      three right lung lobes induced arterial growth in the left lungs of adult rats,
      which was proportionate to the number of lobes removed, the ratio of distal
      pulmonary arteries to alveoli was not normal, and vascular remodeling and
      pulmonary hypertension developed.

PMID- 15516367
TI  - Preexercise metabolic alkalosis induced via bicarbonate ingestion accelerates Vo2
      kinetics at the onset of a high-power-output exercise in humans.
AB  - The present study investigated the effect of preexercise metabolic alkalosis on
      the primary component of oxygen uptake (Vo(2)) kinetics, characterized by tau(1).
      Seven healthy physically active nonsmoking men, aged 22.4 +/- 1.8 (mean +/- SD)
      yr, maximum Vo(2) (Vo(2 max)) 50.4 +/- 4 ml.min(-1).kg(-1), performed two bouts
      of cycling, corresponding to 40 and 87% of Vo(2 max), lasting 6 min each,
      separated by a 20-min pause, once as a control study and a few days later at
      approximately 90 min after ingestion of 3 mmol/kg body wt of NaHCO(3). Blood
      samples for measurements of bicarbonate concentration and hydrogen ion
      concentration were taken from antecubital vein via catheter. Pulmonary Vo(2) was
      measured continuously breath by breath. The values of tau(1) were calculated by
      using six various approaches published in the literature. Preexercise level of
      bicarbonate concentration after ingestion of NaHCO(3) was significantly elevated
      (P < 0.01) compared with the control study (28.96 +/- 2.11 vs. 24.84 +/- 1.18
      mmol/l; P < 0.01), and [H(+)] was significantly (P < 0.01) reduced (42.79 +/-
      3.38 nmol/l vs. 46.44 +/- 3.51 nmol/l). This shift (P < 0.01) was also present
      during both bouts of exercise. During cycling at 40% of Vo(2 max), no significant
      effect of the preexercise alkalosis on the magnitude of tau(1) was found.
      However, during cycling at 87% of Vo(2 max), the tau(1) calculated by all six
      approaches was significantly (P < 0.05) reduced, compared with the control study.
      The tau(1) calculated as in Borrani et al. (Borrani F, Candau R, Millet GY,
      Perrey S, Fuchsloscher J, and Rouillon JD. J Appl Physiol 90: 2212-2220, 2001)
      was reduced on average by 7.9 +/- 2.6 s, which was significantly different from
      zero with both the Student's t-test (P = 0.011) and the Wilcoxon's signed-ranks
      test (P = 0.014).

PMID- 15516368
TI  - Reduction of caveolin-3 expression does not inhibit stretch-induced
      phosphorylation of ERK2 in skeletal muscle myotubes.
AB  - Mechanotransduction is critical to the maintenance and growth of skeletal muscle,
      but the mechanism by which cellular deformations are converted to biochemical
      signals remains unclear. Among the earliest and most ubiquitous responses to
      mechanical stimulation is the phosphorylation and activation of mitogen-activated
      protein kinases, in particular ERK2. Caveolin-3 (CAV-3) binds ERK2 and its
      upstream activators in inactive states on the caveolae of resting muscle.
      Caveolae are deformed by stretch, and it was hypothesized that this deformation
      might disrupt the CAV-3-dependent inhibition of ERK2 to affect stretch-induced
      activation. Stretch-induced phosphorylation of ERK2 in myotubes was both
      amplitude and velocity dependent, consistent with a viscoelastic mechanism, such
      as deformation of caveolae. Chemical disruption of caveolae by cholesterol
      depletion increased ERK2 activation by up to 176%. Small interfering RNA
      oligomers were then used to knock down expression of CAV-3 in cultured myotubes
      before mechanical stimulation, with the expectation that reducing CAV-3
      expression would eliminate the stretch-induced activation of ERK2. Knockdown
      reduced CAV-3 protein content by 55% but did not significantly alter the stretch
      induced increase in ERK2 phosphorylation, suggesting that CAV-3 is not an
      essential element of the mechanotransduction pathway, although the limited extent
      of knockdown limits the strength of this conclusion.

PMID- 15516369
TI  - Experimental muscle pain reduces initial motor unit discharge rates during
      sustained submaximal contractions.
AB  - The aim of this human study was to investigate the effect of experimentally
      induced muscle pain on the modifications of motor unit discharge rate during
      sustained, constant-force contractions. Intramuscular and multichannel surface
      electromyographic (EMG) signals were collected from the right and left tibialis
      anterior muscle of 11 volunteers. The subjects performed two 4-min-long isometric
      contractions at 25% of the maximal dorsiflexion torque, separated by a 20-min
      rest. Before the beginning of the second contraction, hypertonic (painful; right
      leg) or isotonic (nonpainful; left leg) saline was injected into the tibialis
      anterior. Pain intensity scores did not change significantly in the first 150 s
      of the painful contraction. Exerted torque and its coefficient of variation were
      the same for the painful and nonpainful contractions. Motor unit discharge rate
      was higher in the beginning of the nonpainful contraction than the painful
      contraction on the right side [means +/- SE, 11.3 +/- 0.2 vs. 10.6 +/- 0.2
      pulses/s (pps); P < 0.01] whereas it was the same for the two contractions on the
      left side (11.6 +/- 0.2 vs. 11.5 +/- 0.2 pps). The decrease in discharge rate in
      4 min was smaller for the painful (0.4 +/- 0.1 pps) than for the control
      contractions (1.3 +/- 0.1 pps). Initial value and decrease in motor unit
      conduction velocity were not different in the four contractions (right leg, 4.0
      +/- 0.1 m/s with decrease of 0.6 +/- 0.1 m/s in 4 min; left leg, 4.1 +/- 0.1 m/s
      with 0.7 +/- 0.1 m/s decrease). In conclusion, stimulation of nociceptive
      afferents by injection of hypertonic saline did not alter motor unit conduction
      velocity but reduced the initial motor unit discharge rates and the difference
      between initial and final discharge rates during sustained contraction.

PMID- 15516370
TI  - Cyclooxygenase-2 and an early stage of chronic hypoxia-induced pulmonary
      hypertension in newborn pigs.
AB  - Our objective was to determine whether cyclooxygenase (COX)-2-dependent
      metabolites contribute to the altered pulmonary vascular responses that manifest
      in piglets with chronic hypoxia-induced pulmonary hypertension. Piglets were
      raised in either room air (control) or hypoxia for 3 days. The effect of the COX
      2 selective inhibitor NS-398 on responses to arachidonic acid or acetylcholine
      (ACh) was measured in endothelium-intact and denuded pulmonary arteries (100- to
      400-microm diameter). Pulmonary arterial production of the stable metabolites of
      thromboxane and prostacyclin was assessed in the presence and absence of NS-398.
      Dilation to arachidonic acid was greater for intact control than for intact
      hypoxic arteries, was unchanged by NS-398 in intact arteries of either group, and
      was augmented by NS-398 in denuded hypoxic arteries. ACh responses, which were
      dilation in intact control arteries but constriction in intact and denuded
      hypoxic arteries, were diminished by NS-398 treatment of all arteries. NS-398
      reduced prostacyclin production by control pulmonary arteries and reduced
      thromboxane production by hypoxic pulmonary arteries. COX-2-dependent contracting
      factors, such as thromboxane, contribute to aberrant pulmonary arterial responses
      in piglets exposed to 3 days of hypoxia.

PMID- 15516371
TI  - Suppression of pathogen-inducible NO synthase (iNOS) activity in tomato increases
      susceptibility to Pseudomonas syringae.

PMID- 15516372
TI  - Differential insertion of GPI-anchored GFPs into lipid rafts of live cells.
AB  - Partitioning of proteins in cholesterol and sphingolipid enriched plasma membrane
      microdomains, called lipid rafts, is critical for many signal transduction and
      protein sorting events. Although raft partitioning of many signaling molecules
      remains to be determined, glycosylphosphatidyl-inositol (GPI)-anchored proteins
      possess high affinity for lipid rafts and are currently exploited as markers to
      investigate fundamental mechanisms in protein sorting and signal transduction
      events. In this study, we demonstrate that two recombinant GPI-anchored green
      fluorescent proteins (GFP-GPIs) that differ in their GPI signal sequence confer
      distinct localization in plasma membrane microdomains. GFP fused to the GPI
      signal of the decay accelerating factor GFP-GPI(DAF) partitioned exclusively in
      lipid rafts, whereas GFP fused to the GPI signal of TRAIL-R3, GFP-GPI(TRAIL-R3),
      associated only minimally with microdomains. In addition, we investigated the
      unique ability of purified GFP-GPIs to insert into membrane microdomains of
      primary lymphocytes. This cell surface painting allows rapid, stable, and
      functional association of the GPI-anchored proteins with the target cell plasma
      membrane. The distinct membrane localization of the two GFP-GPIs was observed
      irrespective of whether the GPI-anchored molecules were painted or transfected.
      Furthermore, we show that painted GFP-GPI(DAF) was totally dependent on the GPI
      anchor and that the membrane insertion was increased by the addition of raft
      associated lipids such as cholesterol, sphingomyelin, and dipalmitoyl
      phosphatidylethanolamine. Thus, this study provides evidence that different GPI
      signal sequences lead to distinct membrane microdomain localization and that
      painted GFP-GPI(DAF) serves as an excellent fluorescent marker for lipid rafts in
      live cells.

PMID- 15516375
TI  - The colon is a pelvic organ too: taking the Couric challenge.

PMID- 15516373
TI  - Are exercise-induced genes induced by exercise?
AB  - Numerous human in vivo studies on skeletal muscle gene expression have
      investigated the effects of given interventions. These have been founded on the
      assumption that presampling can be regarded as a representative control for
      postintervention sampling. However, many genes are responsive to the metabolic
      status, which varies during the day, so that observed differences in gene
      expression between the pre- and post-sample may therefore be a result of the
      daily variations rather than an intervention. Furthermore, the sampling itself
      can cause a local stress response, which may also influence the expression of
      some genes in later samples from the same localized area. To test this, we
      performed a short-term human endurance exercise study in which muscle biopsies
      were obtained from healthy untrained individuals (n=14) before and in the hours
      after exercise to measure the expression of mRNA for previously reported exercise
      related genes (e.g., PPARgamma coactivator-1alpha (PGC-1alpha), pyruvate
      dehydrogenase kinase 4 (PDK4), MyoD, p21, (heat shock protein 72 (HSP72),
      lipoprotein lipase (LPL), citrate synthase (CS), and glucose transporter 4
      (GLUT4)). To test for changes unrelated to exercise, one half of the subjects did
      not exercise. As suspected, several presumed exercise-induced genes were induced
      even without the exercise. Our data demonstrate that presampling is not always a
      representative control for postintervention sampling, illustrating that use of
      presampling can cause erroneous interpretations of the underlying induction
      signals.

PMID- 15516376
TI  - Colon cancer in women: the need for awareness.

PMID- 15516377
TI  - Vulva: the forgotten pelvic organ.

PMID- 15516378
TI  - Focused ultrasound therapy of vulvar dystrophies: a feasibility study.
AB  - OBJECTIVE: To explore the feasibility and efficacy of focused ultrasound
      treatment of squamous hyperplasia and lichen sclerosus. METHODS: A simple
      randomized phase 2 study was conducted in which a total of 76 patients (45 with
      squamous hyperplasia and 31 with lichen sclerosus) were treated with focused
      ultrasound therapy from 1999 to 2002. Before and after the treatment, the
      therapeutic responses were evaluated based on changes in clinical symptoms and
      signs. Pre- and posttreatment biopsy specimens were also assessed through the
      light and electron microscopic examinations. The positive expressions of CD34 and
      myelin basic protein (MBP) tests with the strepavidin-peroxidase
      immunohistochemistry method were used to evaluate the therapeutic response.
      Statistical analysis was performed using chi2 (McNemar chi2) test and t test.
      RESULTS: After the ultrasound treatment, clinical symptoms were dramatically
      improved with a total response rate of 94.74%. Three to 6 months later the skin
      of treated areas returned to normal appearance. In the 2-year follow-up, 49 of 76
      cases (32 squamous hyperplasia and 17 lichen sclerosus) were cured, 23 (11
      squamous hyperplasia and 12 lichen sclerosus) improved and 4 (2 squamous
      hyperplasia and 2 lichen sclerosus) persisted. The positive expressions of CD34
      and MBP after treatment increased significantly at the treated region (P < .05).
      No major complications occurred. CONCLUSION: Vulvar dystrophy could be
      effectively treated with focused ultrasound therapy. This approach appears to be
      a new promising treatment method, although further studies are still needed.
      LEVEL OF EVIDENCE II-3.

PMID- 15516379
TI  - Botulinum toxin in the treatment of refractory vaginismus.
AB  - OBJECTIVE: To investigate the efficacy of botulinum toxin injection to treat
      women with moderate and severe vaginismus. METHODS: Twenty-four women referred to
      our clinic from February 2002 to February 2004 (mean age 25 years; range 19-34
      years) with third- to fourth-degree vaginismus were recruited for this study.
      These women had previous unsuccessful treatments. Botulinum toxin (150-400 mIU)
      was injected into the puborectalis muscles in 3 sites on each side of the vagina.
      RESULTS: Twenty-three patients (95.8%) had vaginal examinations 1 week
      postoperatively that showed little or no vaginismus, 18 (75%) achieved
      satisfactory intercourse after the first injection, 4 (16.7%) had mild pain, 1
      was cured after a second injection, 1 patient refused vaginal examination and did
      not attempt to have coitus, and another had no coitus as a result of her
      husband's secondary impotence. The women were followed up for a mean of 12.3
      months (range 2-24 months), and there were no cases of recurrence. CONCLUSION: In
      refractory cases of vaginismus when conventional therapies have failed, local
      injection of botulinum toxin can be considered. LEVEL OF EVIDENCE: III.

PMID- 15516380
TI  - Vaginal yeast colonization in nonpregnant women: a longitudinal study.
AB  - OBJECTIVE: We sought to investigate the prevalence and risk factors for vaginal
      yeast colonization over a 1-year period. METHODS: We conducted a longitudinal
      cohort study of 1,248 asymptomatic young women by collecting demographic and
      behavioral data at baseline, 4, 8, and 12 months. RESULTS: Seventy percent of
      women were colonized by vaginal yeast at one or more visits, but only 4% were
      colonized at all 4 visits. Using an adjusted generalized estimating equation
      model, factors associated with vaginal yeast colonization were marijuana use in
      the previous 4 months, depomedroxyprogesterone acetate use in the past 4 months,
      sexual intercourse in the previous 5 days, and concurrent colonization with
      lactobacilli and group B streptococcus. Symptoms of pruritus and vulvovaginal
      burning were associated with yeast colonization, but antifungal use was not.
      CONCLUSION: Recent sexual intercourse and use of injection contraceptives are
      risk factors for yeast colonization. Rates of antifungal use did not show an
      association with yeast colonization. The reporting of antifungal use by women
      lacking yeast colonization suggests that self-diagnosis is inaccurate. LEVEL OF
      EVIDENCE: II-2.

PMID- 15516381
TI  - Treatment of recurrent bacterial vaginosis with tinidazole.
AB  - BACKGROUND: Recurrent bacterial vaginosis is a difficult clinical condition. In
      women with recurrent bacterial vaginosis, relapses are common, even after
      prolonged courses of maintenance therapy. Because of its spectrum of activity,
      tinidazole was used in a patient with recurrent bacterial vaginosis. CASE: A 23
      year-old woman taking oral contraceptives had a single sexual partner. She was
      treated for recurrent bacterial vaginosis with multiple courses of metronidazole
      gel 0.75%, including regimens of maintenance therapy. The patient experienced
      repeated recurrences shortly after stopping treatment. A single course of oral
      tinidazole resulted in a prolonged period where she was free of bacterial
      vaginosis. CONCLUSION: Treatment options for recurrent bacterial vaginosis are
      currently limited. Tinidazole may be a useful option in women with recurrent
      bacterial vaginosis.

PMID- 15516382
TI  - Results of the national study of vaginal birth after cesarean in birth centers.
AB  - OBJECTIVE: Some women wish to avoid a repeat cesarean delivery and believe that a
      midwife-supported vaginal birth after cesarean (VBAC) in a nonhospital setting
      represents their best chance to do so; there is a small, persistent demand for
      out-of-hospital VBACs. We conducted a study to obtain the data necessary to
      formulate an evidence-based policy on this practice. METHODS: We prospectively
      collected data on pregnancy outcomes of 1,913 women intending to attempt VBACs in
      41 participating birth centers between 1990 and 2000. RESULTS: A total of 1,453
      of the 1,913 women presented to the birth center in labor. Twenty-four percent of
      them were transferred to hospitals during labor; 87% of these had vaginal births.
      There were 6 uterine ruptures (0.4%), 1 hysterectomy (0.1%), 15 infants with 5
      minute Apgar scores less than 7 (1.0%), and 7 fetal/neonatal deaths (0.5%). Most
      fetal deaths (5/7) occurred in women who did not have uterine ruptures. Half of
      uterine ruptures and 57% of perinatal deaths involved the 10% of women with more
      than 1 previous cesarean delivery or who had reached a gestational age of 42
      weeks. Rates of uterine rupture and fetal/neonatal death were 0.2% each in women
      with neither of these risks. CONCLUSION: Despite a high rate of vaginal births
      and few uterine ruptures among women attempting VBACs in birth centers, a
      cesarean-scarred uterus was associated with increases in complications that
      require hospital management. Therefore, birth centers should refer women who have
      undergone previous cesarean deliveries to hospitals for delivery. Hospitals
      should increase access to in-hospital care provided by midwife/obstetrician teams
      during VBACs. LEVEL OF EVIDENCE: III.

PMID- 15516383
TI  - Maternal prepregnancy overweight and obesity and the pattern of labor progression
      in term nulliparous women.
AB  - OBJECTIVE: To examine the effect of maternal overweight and obesity on labor
      progression. METHODS: We analyzed data from 612 nulliparous women with a term
      pregnancy that participated in the Pregnancy, Infection, and Nutrition Study from
      1995 to 2002. The median duration of labor by each centimeter of cervical
      dilation was computed for normal-weight (body mass index [BMI] 19.8-26.0 kg/m2),
      overweight (BMI 26.1-29.0 kg/m2), and obese (BMI > 29.0 kg/m2) women and used as
      a measurement of labor progression. RESULTS: After adjusting for maternal height,
      labor induction, membrane rupture, oxytocin use, epidural analgesia, net maternal
      weight gain, and fetal size, the median duration of labor from 4 to 10 cm was
      significantly longer for both overweight and obese women, compared with normal
      weight women (7.5, 7.9, and 6.2 hours, respectively). For overweight women, the
      prolongation was concentrated around 4-6 cm, whereas for obese women, their labor
      was significantly slower before 7 cm. CONCLUSION: Labor progression in overweight
      and obese women was significantly slower than that of normal-weight women before
      6 cm of cervical dilation. Given that nearly one half of women of childbearing
      age are either overweight or obese, it is critical to consider differences in
      labor progression by maternal prepregnancy BMI before additional interventions
      are performed.

PMID- 15516384
TI  - Evaluation of the effect of meconium on assessment of fetal lung maturity status
      by TDxFLM II testing.
AB  - OBJECTIVE: To evaluate the effect of meconium contamination on the TDxFLM II
      assay. METHODS: Amniotic fluid was collected from patients undergoing
      amniocentesis for obstetric indications between 31 and 40 weeks of gestation. A
      baseline TDxFLM II value was obtained and compared with amniotic fluid
      contaminated with 1%, 5%, and 10% meconium by weight. RESULTS: Twenty-one samples
      were studied, and in every case the TDxFLM II value decreased once the meconium
      was added. There was no consistent rate of decrease that correlated with the
      percentage of meconium added. CONCLUSION: Meconium contamination decreases the
      TDxFLM II value. A clinician who performs this test in the presence of meconium
      can be reassured that the contamination will not give an artificially elevated
      result. If the result is in the mature range, one can be confident that the
      result would only be higher if meconium were not present.

PMID- 15516385
TI  - Trends in congenital malformations, 1974-1999: effect of prenatal diagnosis and
      elective termination.
AB  - OBJECTIVE: To examine trends in congenital malformations, elective terminations
      for malformations and correlates for the decision to terminate a pregnancy with a
      malformation. METHODS: All malformed liveborn and stillborn infants and elective
      terminations for malformations were identified in a large urban tertiary center
      and general hospital for the years 1974, 1979, 1984, 1989, 1994, and 1999. Nine
      hundred and fifty-four women with malformed infants, who had always planned to
      deliver at the hospital, were identified. Prenatal screening by ultrasonography
      or amniocentesis before 24 weeks of gestation, severity rating of the
      malformation, parity, marital status, race, level of education, insurance status,
      and pregnancy history were determined RESULTS: In each of these 6 years, about 2%
      of newborn infants had a major malformation. The rate of prenatal screening by
      ultrasonography and amniocentesis before 24 weeks increased from 7% in the years
      1974 and 1979 to 61% in the years 1984 and 1989 to 89% in the years 1994 and
      1999. Elective termination increased from less than 1% in the years 1974 and 1979
      to 18% to 20% in the years 1984, 1989, 1994, and 1999. Pregnancies with fatal and
      severe conditions were much more likely to be terminated electively than
      pregnancies with moderate or mild conditions (odds ratio 53.3; 95% confidence
      interval 22.7-124.7) CONCLUSION: The introduction of routine prenatal screening
      and the subsequent increase in elective termination for malformed fetuses means
      that the inclusion of terminated pregnancies in malformation surveillance
      programs is necessary to study prevalence and risk factors in the epidemiology of
      malformations.

PMID- 15516386
TI  - Reproductive history and endometriosis among premenopausal women.
AB  - OBJECTIVE: To clarify the temporal complexities of the relation between
      reproductive factors and endometriosis. METHODS: We analyzed 10 years of
      prospective data from the Nurses' Health Study II cohort. Information was
      obtained through questionnaires sent every 2 years to 116,678 women aged 25-42
      years when enrolled in 1989. Cox proportional hazards models were used to adjust
      for age, calendar time, and confounding variables. RESULTS: During 726,205 woman
      years of follow-up, 1,721 cases of laparoscopically confirmed endometriosis were
      reported among women with no past infertility. Greater incidence was observed
      among women with an earlier age at menarche (rate ratio of 1.3 comparing menarche
      at age < 10 to age 12 years; 95% confidence interval [CI] 1.0-1.8; P value, test
      for trend < .001) and shorter cycle length during late adolescence (rate ratio of
      1.3 comparing < 26 days to 26-31 days; 95% CI 1.1-1.5). Time to cycle regularity
      was not associated with risk. Among parous women, a linear decrease in risk was
      observed with number of liveborn children (rate ratio of 0.5 comparing > 3 with 2
      children; 95% CI 0.4-0.7; P value, test for trend < .001) and lifetime duration
      of lactation if time since last birth was less than 5 years (rate ratio of 0.2
      comparing > 23 months with never; 95% CI 0.1-0.4; P value, test for trend <
      .001). CONCLUSION: Hormonal and anatomical changes associated with menstruation
      and pregnancy may affect the rate of laparoscopically confirmed endometriosis.
      Within this cohort, risk was greatest among nulliparous women with earlier age at
      menarche and shorter menstrual cycles. Among parous women, parity and lifetime
      duration of lactation were associated with decreased risk.

PMID- 15516387
TI  - Decline of serum human chorionic gonadotropin and spontaneous complete abortion:
      defining the normal curve.
AB  - OBJECTIVE: We sought to estimate a standard curve of serum human chorionic
      gonadotropin (hCG) decline that characterizes spontaneous abortion. METHODS: Data
      were extracted from a clinical database of women with symptomatic early
      pregnancies and nondiagnostic ultrasonography who required follow-up with serial
      hCG levels. The evaluation was restricted to women who had a pregnancy of unknown
      location, a decrease in serum levels, and who were ultimately diagnosed with
      miscarriage (a decrease in serum hCG to < 5 mIU/mL in the absence of surgical
      intervention or confirmation of products of conception after dilation and
      curettage). The starting point of the curve was the hCG concentration at
      presentation, with serial levels plotted until the time of definitive diagnosis.
      Semiparametric statistical techniques were used to characterize the shape of the
      curve. We present slopes for the decrease in log hCG levels and the projected
      rate of fall. RESULTS: Of the 1,543 patients, 710 were diagnosed with
      miscarriage. A quadratic curve for log hCG with a steeper rate of decline for
      large initial hCG values best described the pattern of change. One curve could
      not fully estimate the decline because the rate was dependent on the initial hCG
      level. In other words, more rapid decline was associated with a higher starting
      concentration. The rate of decline ranged from 21% to 35% at 2 days and 60% to
      84% at 7 days, depending on initial hCG value. CONCLUSION: The rate of hCG
      decrease in spontaneous abortions is described by a quadratic profile, with a
      faster decline in hCG value with higher presentation levels. A rate of decline
      less than 21% at 2 days or 60% at 7 days suggests retained trophoblasts or an
      ectopic pregnancy.

PMID- 15516388
TI  - Pelvic symptoms in women with pelvic organ prolapse.
AB  - OBJECTIVE: To assess symptoms of bladder, bowel, and sexual function in women
      with pelvic organ prolapse and to compare symptoms by different degrees of
      prolapse. METHODS: This retrospective study used data from 352 women with
      prolapse or urinary incontinence. The pelvic organ prolapse quantification
      measurements, as well as responses to 3 self-administered questionnaires
      assessing urinary, bowel, and sexual function were used. For each individual,
      pelvic organ prolapse quantification measures of prolapse were obtained in
      centimeters in relation to the hymen for 3 compartments: anterior vagina, vaginal
      apex or cervix, and posterior vagina. Data were analyzed by comparing the
      frequency of symptoms to centimeter measures of the most advanced prolapse
      (regardless of site) and the other compartments of prolapse. RESULTS: Of the 330
      patients available for analysis, 2.4% had stage I, 46.1% had stage II, 48.2% had
      stage III, and 3.3% had stage IV prolapse. The average age was 58.8 years (+/-
      12.1), with a median parity of 3. Forty-eight percent were postmenopausal and
      taking estrogen, 27% were postmenopausal and not taking estrogen, and 25% were
      premenopausal. Patients who had stress incontinence symptoms had less advanced
      prolapse (median 5 cm less prolapse in the apical compartment) than patients
      without stress incontinence. Women who required manual assistance to urinate had
      more advanced prolapse (median 3.5 cm more prolapse in the most advanced
      compartment) than those who did not. Patients with urinary urgency and urge
      incontinence also had less advanced prolapse, although the differences were
      smaller than for stress incontinence (median 3 cm difference or less). There were
      no clinically significant differences in any compartment for symptoms related to
      sexual or bowel function. CONCLUSION: Women with more advanced prolapse were less
      likely to have stress incontinence and more likely to manually reduce prolapse to
      void; however, prolapse severity was not associated with sexual or bowel
      symptoms. LEVEL OF EVIDENCE: II-2.

PMID- 15516389
TI  - Hemorrhagic complications associated with tension-free vaginal tape procedure.
AB  - OBJECTIVE: We sought to assess the frequency, symptoms, and management of
      hemorrhagic complications in patients undergoing tension-free vaginal tape (TVT)
      procedure. METHODS: Over a 5-year period the clinical course of all 336
      consecutive patients undergoing TVT procedure in our hospital was recorded,
      including diagnostic approaches and management strategies for both increased
      intraoperative blood loss and clinically relevant hematoma. RESULTS: In 87
      patients (26%), TVT procedure was combined with other gynecologic surgeries, and
      249 patients (74%) underwent TVT alone. In 7 cases (2.1%), increased
      intraoperative blood loss (250-400 mL) was managed by electro-coagulation, manual
      compression, tamponade, and/or insertion of a drain. The postoperative course in
      these patients was uncomplicated. In 14 women (4.1%) who did not show increased
      bleeding during the operation, retropubic hematoma developed, the volume of which
      exceeded 300 mL in 4 cases (1.2%). These required surgical intervention. In the
      first case we performed open laparotomy, whereas in the following cases the
      hematoma could be successfully drained by endoscopy. Postoperative development of
      a hematoma did not lead to recurrence of stress incontinence. CONCLUSION:
      Bleeding complications during or after TVT procedure are rare events. Increased
      intraoperative bleeding can usually be managed with electro-coagulation,
      compression, and drainage. LEVEL OF EVIDENCE: II-3.

PMID- 15516390
TI  - Repeat measurement of cervical length after successful tocolysis.
AB  - OBJECTIVE: To measure the ultrasonographic cervical length in undelivered women
      after successful tocolysis for preterm labor, and to determine whether this could
      improve the predictive value of cervical length measured before initiation of
      tocolysis on the risk of preterm delivery. METHODS: This was a prospective study
      of patients admitted and treated for uterine contractions at 24(+0) to 33(+6)
      weeks of gestation with a cervical length of 26 mm or less by transvaginal
      ultrasonography on admission. Intravenous tocolysis was stopped when delivery was
      delayed by 48 hours, and cervical length was remeasured before discharge. The
      primary outcome was preterm delivery, defined by a delivery before 37 weeks.
      Predictive analysis was based on logistic models, with estimated odds ratios and
      95% confidence interval. RESULTS: One hundred and nine patients were included in
      the study. The median (first, third quartile) cervical length on admission was 18
      (13, 22) mm. The median (first, third quartile) variation in cervical length
      after tocolysis was stopped was 3 (0, 8) mm, and ranged from -13 to 26 mm. The
      median (first, third quartile) time interval from tocolysis to delivery was 53.0
      (35.0, 70.0) days, with 45 (41.3%) patients delivered before 37 weeks. After
      adjustment for cervical length before admission and parity and gestational age on
      admission, the assessment of the variation in cervical length after successful
      tocolysis did not improve the predictive value of transvaginal sonography for the
      risk of preterm delivery (odds ratio 0.97; 95% confidence interval 0.90-1.03; P =
      .27). CONCLUSION: To repeat ultrasonographic cervical length measurement after
      successful tocolysis for preterm labor is useless.

PMID- 15516391
TI  - The appropriateness of red blood cell transfusions in the peripartum patient.
AB  - OBJECTIVE: Despite published guidelines, numerous studies have consistently shown
      that a significant proportion of red blood cell (RBC) transfusions are
      unnecessary. The purpose of this study was to evaluate the reasons for and the
      appropriateness of RBC transfusions in the peripartum patient. METHODS: We
      reviewed all RBC transfusions given to peripartum inpatients at Sunnybrook and
      Women's College Health Sciences Centre in Toronto, Ontario, Canada between April
      1994 and July 2002. Appropriateness of RBC transfusion was ascertained using
      current hospital transfusion guidelines. RESULTS: We identified 33,795 obstetrics
      related admissions. In 218 admissions (0.65% of all admissions), an RBC
      transfusion was given to 216 women. There were 83 vaginal deliveries, 94
      deliveries by cesarean, and 42 operations (for ectopic pregnancies or dilatation
      and curettage). A total of 779 RBC units were transfused (median, 2 units per
      woman; range, 1-32), most commonly for postpartum bleeding (34% of cases). There
      were 16 adverse events from transfusion recorded. According to guidelines, 248 of
      the transfused RBC units (32%) were not appropriate. In addition, in 24 patients
      (11%) the mean corpuscular volume on admission to the hospital for delivery was
      less than or equal to 80 fL. CONCLUSION: A significant proportion of RBC
      transfusions given to peripartum women are inappropriate. Educational programs
      that promote adherence to transfusion guidelines might help reduce exposure to
      RBC transfusion. Aggressive oral and intravenous iron therapy might have
      prevented transfusion in 11% of the women in the cohort who were possibly iron
      deficient.

PMID- 15516392
TI  - Oxytocin requirements at elective cesarean delivery: a dose-finding study.
AB  - OBJECTIVE: Oxytocin is frequently used by intravenous bolus and infusion to
      minimize blood loss and prevent postpartum hemorrhage at cesarean delivery.
      Current dosing regimens are arbitrary whereas large doses may pose a serious risk
      to the mother. The purpose of this study was to estimate the minimum effective
      intravenous bolus dose of oxytocin (ED90) required for adequate uterine
      contraction at elective cesarean in nonlaboring women. METHODS: A randomized,
      single-blinded study was undertaken in 40 healthy term pregnant women presenting
      for elective cesarean under spinal anesthesia. Oxytocin was administered by bolus
      according to a biased coin up-and-down sequential allocation scheme with
      increments or decrements of 0.5 IU. Uterine contraction was assessed by the
      obstetrician, who was blinded to the dose of oxytocin, as either satisfactory or
      unsatisfactory. After achieving sustained uterine contraction, an infusion of 40
      mU/min of oxytocin was started. Oxytocin-induced adverse effects and
      intraoperative complications were recorded and blood loss was estimated. Data
      were interpreted by parametric analysis based on logistic regression model and
      nonparametric analyses at 95% confidence intervals (CIs). RESULTS: The ED90 of
      oxytocin as determined by logistic regression model fitted to the data was
      estimated to be 0.35 IU (95% CI 0.18-0.52 IU), with nonparametric estimates of
      97.1% (95% CI 84.9-99.8%) response rate at 0.5 IU, and 100% (95% CI 92.2-100%) at
      1.0 IU. The estimated blood loss was 693 +/- 487 mL (mean +/- standard
      deviation). CONCLUSION: The bolus dose of oxytocin used at elective cesarean
      deliveries in nonlaboring women can be significantly reduced while maintaining
      effective uterine contraction. Alteration in practice will likely reduce the
      potential adverse effects of this drug when given in large bolus doses, but may
      require modification of the techniques to remove the placenta.

PMID- 15516393
TI  - Obstetric implications of antepartum corticosteroid therapy for HELLP syndrome.
AB  - OBJECTIVE: We reviewed the impact of intravenous high-dose corticosteroid
      administration for preterm hemolysis, elevated liver enzymes, low platelets
      (HELLP) syndrome on vaginal delivery rate and degree of clinically significant
      thrombocytopenia. METHODS: Retrospective analysis of 1991-2000 HELLP syndrome
      (platelets < 100,000/uL, lactate dehydrogenase > 600 IU/L, aspartate
      aminotransferase and/or alanine aminotransferase > 70 IU/L) data focusing on
      labor inductions for gestations of less than 34 weeks and increase in platelet
      count sufficient to permit regional anesthetic techniques. RESULTS: Antepartum
      high-dose corticosteroid use increased from 32% (1991-1995) to 67% (1996-2000)
      for 350 patients studied (n = 199, < 34 weeks; n = 151, > 34 weeks).
      Corresponding vaginal delivery rates were 32% for gestations of less than 30
      weeks, 61% at 30-31 weeks, and 62% at 32-33 weeks. Similarly, 27% of patients
      with a platelet count of less than 75,000/uL and 52% with a platelet count of
      less than 100,000/uL who received high-dose corticosteroids during the study
      interval subsequently achieved a 100,000/uL threshold in time to perform regional
      anesthesia for delivery. CONCLUSION: Administration of intravenous high-dose
      corticosteroids for preterm HELLP syndrome increases probability of successful
      labor induction and candidacy for regional anesthesia. LEVEL OF EVIDENCE: II-3.

PMID- 15516394
TI  - Seasonal variation in preeclampsia based on timing of conception.
AB  - OBJECTIVE: Studies have suggested that the incidence of preeclampsia may be
      partially dependent on the month or season of delivery. We sought to evaluate
      whether preeclampsia occurs seasonally in our population and whether the timing
      of conception or delivery is more strongly associated with risk. METHODS: Between
      January 1995 and August 2003, we identified 142 primiparous women with singleton
      pregnancies who met the American College of Obstetricians and Gynecologists'
      definition for preeclampsia and compared them with 7,762 primiparous control
      deliveries. We analyzed rates of preeclampsia by individual month and 3-month
      seasonal blocks based on conception and delivery. Data were analyzed with the
      chi2 test, and logistic regression and odds ratios were calculated where
      appropriate. RESULTS: Preeclampsia occurred in 1.8% of singleton primiparous
      gestations (142/7,904). Cases were younger than controls (26.5 +/- 5.6 versus
      28.0 +/- 0 6.0 years, P < .003), of similar race (97% white versus 96% white, P =
      .69), and equally likely to have a female child (45% versus 48%, P = .41). We
      found no significant association of month (logistic regression P = .20) of
      delivery with the risk of preeclampsia. There was a significant association of
      month (P = .003) of conception with risk of preeclampsia. Conception during the
      summer months had the highest risk (incidence 2.3%; odds ratio 1.7; 95%
      confidence limits 1.06, 2.75) compared with spring (incidence 1.4%). Fall (1.7%)
      and winter (1.6%) conceptions were associated with intermediate rates of
      preeclampsia. CONCLUSION: We identified a seasonal variation in preeclampsia that
      appears to be more strongly related to timing of conception than to the timing of
      delivery. The highest incidence of preeclampsia was associated with conception in
      the summer months. LEVEL OF EVIDENCE: II-2.

PMID- 15516395
TI  - Anthropometric parameters in infants of gestational diabetic women with strict
      glycemic control.
AB  - OBJECTIVE: Differences in weight and body composition have been reported between
      infants of nondiabetic and diabetic mothers. These differences may explain the
      propensity for shoulder dystocia in the diabetic population. We investigated
      whether differences in anthropometric measurements still exist between infants of
      nondiabetic and diabetic mothers following strict glycemic control. METHODS: This
      was a prospective cohort study. The study group included infants of well
      controlled gestational diabetic mothers (mean capillary glucose less than 100
      mg/dL). Controls were infants of nondiabetic mothers matched for gender,
      gestational age, ethnicity, and birth weight. Only singleton term pregnancies
      were included. Both groups were studied within 24 hours of delivery. The
      following measurements were obtained: birth weight, infant length, femur length,
      head, chest, abdomen and thigh circumferences, and biacromial distance. Student t
      tests were used to compare the measured parameters between groups. P < .05 was
      considered significant. A sample size of 63 subjects in each group was needed to
      demonstrate a difference of 0.5 cm (+/- 1.0 cm) of the biacromial distance
      between the 2 groups, which we considered clinically significant, with a
      probability of 95% and power of 80%. RESULTS: Sixty seven infants in each group
      were included in the study. Anthropometric measurements did not differ
      significantly between the groups. We did a secondary analysis on neonates who
      weighed 4,000 g or more at birth. Anthropometric measurements again did not
      differ significantly between the groups. CONCLUSION: Anthropometric measurements
      of infants of mothers with well-controlled gestational diabetes do not differ
      from infants of nondiabetic mothers. LEVEL OF EVIDENCE: II-2.

PMID- 15516396
TI  - Vascular reactivity in preeclampsia assessed noninvasively using maternal
      brachial artery hyperemic response.
AB  - OBJECTIVE: To estimate if women with preeclampsia had measurable differences in
      the brachial artery waveforms after blood flow occlusion. METHODS: In a cross
      sectional study, 14 preeclamptic and 28 matched normotensive women were assessed.
      Hemolysis, elevated liver enzymes, low platelets syndrome patients were excluded.
      All patients had baseline brachial Doppler flow velocities while resting in the
      left lateral position and after a 60-second forearm occlusion. Doppler waveforms
      were analyzed from the brachial artery 30-45 seconds after the release of the
      blood pressure cuff. We analyzed the classical Doppler waveform parameters of
      systolic diastolic, mean velocity and pulsatility index, time taken to achieve
      peak systolic velocity, systolic acceleration time, the percentage of time in
      each cycle to achieve peak systolic velocity, and systolic acceleration from 3
      waveforms. Comparison of the percentage change in each of these parameters
      between the groups was done using t tests. RESULTS: Before brachial artery
      occlusion, systolic acceleration time was significantly less in the preeclamptic
      group (77.5 +/- 14.4 milliseconds versus 93.2 +/- 11.7 milliseconds; (P < .001).
      After occlusion, the percentage change in the systolic acceleration and systolic
      acceleration time was increased in the normotensive group (P < .001). CONCLUSION:
      There was significantly increased impedance to blood flow downstream assessed by
      Doppler waveform analysis after a period of forearm ischemia (blood pressure
      occlusion) in the women with preeclampsia. LEVEL OF EVIDENCE: II-1.

PMID- 15516397
TI  - Hysteroscopy and cytology in endometrial cancer.
AB  - OBJECTIVE: To estimate the effect of preoperative diagnostic hysteroscopy on
      peritoneal cytology in patients with endometrial cancer. METHODS: A total of 256
      charts were reviewed. Two cohorts were established based on diagnosis by
      hysteroscopy or blind endometrial sampling via either endometrial biopsy or
      dilatation and curettage (D&C). Malignant or suspicious peritoneal cytology was
      the primary outcome. Cohorts were compared using logistic regression to correct
      for potential confounders of stage and grade. RESULTS: A total of 204 cases were
      diagnosed by endometrial biopsy or D&C, whereas 52 were identified by
      hysteroscopy. In the endometrial biopsy or D&C arm, 14 of 204 (6.9%) patients had
      malignant or suspicious cytology compared with 7 of 52 (13.5%) patients in the
      hysteroscopy arm (P = .15). After logistic regression controlling for stage and
      grade, the odds ratio for positive cytology after hysteroscopy was 3.88 (95%
      confidence interval 1.11,13.6; P = .03). Four of the 52 (7.7%) cases diagnosed by
      hysteroscopy were stage IIIA due to cytology alone compared with 3 of the 204
      (1.4%) cases diagnosed by endometrial biopsy or D&C (P = .03). CONCLUSION:
      Hysteroscopy appears to be associated with an increased rate of malignant
      cytology after controlling for confounders of stage and grade. Further, there
      appears to be an association between hysteroscopy and upstaging patients due to
      cytology alone. LEVEL OF EVIDENCE: II-2.

PMID- 15516398
TI  - Is prior uterine surgery a risk factor for adenomyosis?
AB  - OBJECTIVE: The objective of our study was to assess whether prior uterine surgery
      is a risk factor for adenomyosis. METHODS: Medical records of women who had a
      hysterectomy for benign conditions between January of 1995 and June of 2002 were
      reviewed. Women with and without adenomyosis were compared with respect to
      history of prior uterine surgery, such as cesarean delivery, myomectomy,
      endometrial ablation, dilation and evacuation, and dilation and curettage.
      RESULTS: Of 873 completed records available, 412 patients (47.1%) had
      adenomyosis. Mean age and race distribution were similar between the 2 groups.
      The group with adenomyosis had significantly higher gravidity (P < .001) and
      parity (P = .004), but smaller uterine size (P < .001) and uterine weight (P <
      .001). Univariable analysis for each aforementioned specific surgical procedure
      did not indicate a significant difference between women with and without
      adenomyosis. However, history of any prior uterine surgery increased the risk of
      adenomyosis (48.8% and 41.0%, odds ratio 1.37, 95% confidence interval 1.05-1.79)
      on univariable analysis. This association remained significant when all of the
      factors were combined in a multivariable logistic regression model. CONCLUSION:
      In this study, we found a significantly increased risk of adenomyosis with prior
      uterine surgery. The absence of significant association with any specific
      surgical procedure is possibly the result of a smaller number of subjects in each
      individual group. LEVEL OF EVIDENCE: II-3.

PMID- 15516399
TI  - Tuboovarian abscess 12 years after total abdominal hysterectomy.
AB  - BACKGROUND: Pelvic inflammatory disease affects nearly 1 million women in the
      United States each year, and 10% of cases are complicated by the formation of
      tuboovarian abscess. Most tuboovarian abscesses occur in women with intact
      cervical and uterine anatomy. CASE: A 38-year-old woman presented with acute
      abdominal pain, fever, chills, nausea and vomiting, and the presence of a pelvic
      mass. Surgical exploration revealed a tuboovarian abscess. The patient's history
      was significant for total abdominal hysterectomy for cervical dysplasia 12 years
      before presentation. CONCLUSION: This case challenges the current theories for
      the pathogenesis of tuboovarian abscess. Furthermore, it supports the importance
      of considering tuboovarian abscess in the differential diagnosis with acute
      abdominal pain and pelvic mass despite previous hysterectomy.

PMID- 15516400
TI  - Hormone therapy prescribing patterns in the United States.
AB  - OBJECTIVE: We sought to examine prescribing patterns (prevalence and rates of
      initiation and discontinuation) for estrogen plus progestin (hormone therapy [HT]
      and estrogen alone [ET]) in the United States in the 2 years before the published
      results of Women's Health Initiative's (WHI) HT trial's early termination and for
      5 months after their release. METHODS: We conducted an observational cohort study
      of 169,586 women aged 40-80 years who were enrolled in 5 health maintenance
      organizations in the United States to estimate the prevalence of HT and ET and
      discontinuation and initiation rates between September 1, 1999, to June 31, 2002
      (baseline), and December 31, 2002 (follow-up). We used automated pharmacy data to
      identify all oral and transdermal estrogen and progestin dispensed during the
      study period. RESULTS: The prevalence of HT declined 46% from baseline to follow
      up (14.6% to 7.9%); ET use declined 28% during the same period (12.6% to 9.1%).
      The discontinuation of HT increased almost immediately, from 2.5% at baseline to
      13.8% in October 2002. We saw an immediate decrease in HT and ET initiation
      rates, from 0.4% and 0.3% at baseline, respectively, to 0.2% for HT and ET at
      follow-up. CONCLUSION: The diffusion of the WHI HT trial results had an immediate
      impact on the discontinuation of HT and ET and is likely responsible for the 46%
      and 28% decline in the initiation of these respective therapies. Further
      exploration of why women continue to use HT and identification of methods for
      addressing reasons for continued use are indicated. LEVEL OF EVIDENCE: II-2.

PMID- 15516401
TI  - Antibiotics for preterm rupture of the membranes: a systematic review.
AB  - OBJECTIVE: We sought to evaluate the administration of antibiotics to pregnant
      women with preterm rupture of membranes (PROM). DATA SOURCES: We collected data
      by using the Cochrane Controlled Trials Register and MEDLINE. METHODS OF STUDY
      SELECTION: We included randomized controlled comparisons of antibiotic versus
      placebo (14 trials, 6,559 women). TABULATION, INTEGRATION, AND RESULTS:
      Antibiotics were associated with a statistically significant reduction in
      maternal infection and chorioamnionitis. There also was a reduction in the number
      of infants born within 48 hours and 7 days and with the following morbidities:
      neonatal infection (relative risk [RR] 0.67, 95% confidence interval [CI] 0.52
      0.85), positive blood culture (RR 0.75, 95% CI 0.60-0.93), use of surfactant (RR
      0.83 95% CI 0.72-0.96), oxygen therapy (RR 0.88, 95% CI 0.81-0.96), and abnormal
      cerebral ultrasound scan before discharge from hospital (RR 0.82, 95% CI 0.68
      0.99). Perinatal mortality was not significantly reduced (RR 0.91, 95% CI 0.75
      1.11). A benefit was present both in trials where penicillins and erythromycin
      were used. Amoxicillin/clavulanate was associated with a highly significant
      increase in the risk of necrotizing enterocolitis (RR 4.60, 95% CI 1.98-10.72).
      CONCLUSION: The administration of antibiotics after PROM is associated with a
      delay in delivery and a reduction in maternal and neonatal morbidity. These data
      support the routine use of antibiotics for women with PROM. Penicillins and
      erythromycin were associated with similar benefits, but erythromycin was used in
      larger trials and, thus, the results are more robust. Amoxicillin/clavulanate
      should be avoided in women at risk of preterm delivery because of the increased
      risk of neonatal necrotizing enterocolitis. Antibiotic administration after PROM
      is beneficial for both women and neonates.

PMID- 15516402
TI  - Vaginal-perianal compared with vaginal-rectal cultures for identification of
      group B streptococci.
AB  - OBJECTIVE: To estimate whether the rates of recovery of group B streptococci from
      combined vaginal and perianal cultures and combined vaginal and rectal cultures
      are equivalent. METHODS: We performed a prospective cohort study of vaginal
      perianal versus vaginal-rectal culture for group B streptococci. Two hundred
      pregnant women in the third trimester were enrolled. Three specimens were
      collected from each patient in the following order: lower third of the vagina,
      perianal skin, and rectum. Each specimen was cultured serially in selective broth
      media, then on sheep's blood agar. Suspicious colonies were confirmed by latex
      agglutination. Culture positivity rates from the combined sites of vagina and
      perianal skin were compared with vagina and rectum. Laboratory personnel were
      blinded to the collection site of each individual swab. RESULTS: Of the 200
      subjects, 71 (36%) had a positive culture from at least 1 site. Vaginal culture
      was positive in 55 patients (28%), compared with 48 patients (24%) with positive
      perianal cultures and 50 patients (25%) with positive rectal cultures. Results of
      combined vaginal and perianal cultures were positive in 68 patients (34%);
      results of combined vaginal and rectal cultures were positive in 67 patients
      (34%) (P = 1.0). CONCLUSION: The group B streptococci detection rate from vaginal
      perianal specimens is not significantly different from the detection rate from
      vaginal-rectal specimens. Therefore, pregnant women do not need to be subjected
      to the discomfort of collection of a rectal specimen. LEVEL OF EVIDENCE: II-2.

PMID- 15516403
TI  - Perinatal infections due to group B streptococci.
AB  - Group B streptococci (GBS) emerged dramatically in the 1970s as the leading cause
      of neonatal infection and as an important cause of maternal uterine infection. We
      review the epidemiology, diagnosis, and therapy of GBS perinatal infection. In
      1996, the first national consensus guidelines were released. Since then, there
      has been a 70% reduction in early-onset neonatal GBS infection, but no decrease
      in late-onset neonatal GBS disease. In 2002, new national guidelines were
      released recommending 1) solely a screen-based prevention strategy, 2) a new
      algorithm for patients with penicillin allergy, and 3) more specific practices in
      certain clinical scenarios. Yet many clinical issues remain, including
      implementation of new diagnostic techniques, management of preterm rupture of
      membranes, use of alternative antibiotic approaches, improvement of compliance,
      prevention of low birth weight infants, emergence of resistant organisms, and
      vaccine development.

PMID- 15516404
TI  - Natural history of grade 1 cervical intraepithelial neoplasia in women with human
      immunodeficiency virus.
AB  - OBJECTIVE: We sought to estimate rates of progression and regression of grade 1
      cervical intraepithelial neoplasia (CIN 1) among women with human
      immunodeficiency virus (HIV). METHODS: In a multicenter prospective cohort study,
      HIV-seropositive and HIV-seronegative women were evaluated colposcopically after
      receiving an abnormal cytology test result between November 1994 and September
      2002. Women with CIN 1 were included, except those who had undergone
      hysterectomy, cervical therapy, or had CIN 2-3 or cervical cancer. Those women
      who were included were followed cytologically twice yearly, with colposcopy
      repeated for atypia or worse. RESULTS: We followed 223 women with CIN 1 (202 HIV
      seropositive and 21 HIV seronegative) for a mean of 3.3 person-years. Progression
      occurred in 8 HIV-seropositive women (incidence density, 1.2/100 person-years;
      95% confidence interval [CI] 0.5-2.4/100 person-years) and in no HIV seronegative
      women. Regression occurred in 66 (33%) HIV-seropositive women (13/100 person
      years, 95% CI 10-16/100 person-years) versus 14 (67%) seronegative women (32/100
      person-years, relative risk 0.40, 95% CI 0.25-0.66; P < .001). In multivariate
      analysis, regression was associated with human papillomavirus (HPV) detection
      (hazard ratio [HR] for low risk 0.28, 95% CI 0.13-0.61, P = .001; and for high
      risk 0.34, 95% CI 0.20-0.55, P < .001 versus no HPV detected) and Hispanic
      ethnicity (HR 0.48, 95% CI 0.230.98; P = .04); HIV serostatus was only marginally
      linked to regression (HR 0.52, 95% CI 0.27-1.03; P = .06), but seropositive women
      were less likely to regress when analysis was limited to 146 women with HPV
      detected at CIN 1 diagnosis (HR 0.18, 95% CI 0.05-0.62; P = .006). CONCLUSION:
      Grade 1 cervical intraepithelial neoplasia infrequently progresses in women with
      HIV. Thus, observation appears safe absent other indications for treatment. LEVEL
      OF EVIDENCE: II-1.

PMID- 15516405
TI  - Squamous cell carcinoma of the cervix producing granulocyte colony-stimulating
      factor.
AB  - BACKGROUND: Marked leukocytosis is occasionally observed in patients with a
      malignant nonhematopoietic tumor. Granulocyte colony-stimulating factor (G-CSF)
      may be responsible for this phenomenon. We report a case of G-CSF-producing
      squamous cell carcinoma of the cervix that showed marked leukocytosis. CASE: A 71
      year-old Japanese woman was admitted for further investigation for leukocytosis.
      Her white blood cell (WBC) count had been gradually increasing over a period of
      10 months. Laboratory data on admission revealed marked leukocytosis, with a WBC
      count of 30,400/microL, which consisted primarily of mature granulocytes (93%).
      Her serum G-CSF level was significantly elevated. However, there was no evidence
      of infection or hematopoietic disorders. Further examinations showed stage IIIb
      cervical cancer. The pathological diagnosis was squamous cell carcinoma of the
      nonkeratinizing type. Immunohistochemical staining of the biopsied specimens
      confirmed the production of G-CSF protein by the tumor cells. The patient was
      successfully treated by radiation therapy. Her WBC count returned to a normal
      level (3,700/microL). Her serum G-CSF level also decreased. The patient is alive
      without evidence of recurrence at 8 months after the treatment. CONCLUSION: It is
      suggested that the leukocytosis manifested in this patient was due to G-CSF
      produced by the tumor. It was possible to use the WBC count and serum G-CSF
      levels as additional tumor markers.

PMID- 15516406
TI  - Gender bias against male obstetrician-gynecologists in women's magazines.
AB  - OBJECTIVE: To evaluate whether gender bias against male obstetricians and other
      male physicians is found in popular women's magazines. METHODS: Issues of
      Cosmopolitan, Fitness, Glamour, Good Housekeeping, Ladies Home Journal, and
      Redbook were searched for medically related articles from July 2001 to December
      2002. The articles were analyzed for the number and gender of physicians quoted,
      the number of gender-specific pronouns and negative gender-specific pronouns, and
      the number of pictured physicians by gender. RESULTS: Female obstetrician
      gynecologists were interviewed as health care resources 47-80% of the time, which
      is higher than expected when compared with the American College of Obstetricians
      and Gynecologists membership numbers (P < .01). A similar phenomenon was found
      when discussing physicians in general (P < .001). Female physicians were more
      than 20 times more likely to have an identifying photograph. Pronouns used to
      identify negative physician traits accounted for 17% of the total pronouns when
      identifying female obstetrician-gynecologists and other specialties but accounted
      for 92% of the total pronouns when identifying male obstetrician-gynecologists
      and 77% of the pronouns when identifying other male physicians (P < .001). In 5
      magazines, physicians had their quoted gender pronouns changed from gender
      neutral to reflect female-specific pronouns. CONCLUSION: In women's interest
      magazines, there is a gender bias against male obstetrician-gynecologists as well
      as male physicians in general. This may serve to undermine the physician-patient
      relationship and be detrimental to women's health care. LEVEL OF EVIDENCE: III.

PMID- 15516409
TI  - Emergency contraception: politics trumps science at the U.S. Food and Drug
      Administration.

PMID- 15516411
TI  - Recruiting.

PMID- 15516414
TI  - Association of rheumatologic disease with preeclampsia.

PMID- 15516412
TI  - Randomized comparison of chromic versus fast-absorbing polyglactin 910 for
      postpartum perineal repair.

PMID- 15516416
TI  - Natural history of bacterial vaginosis and intermediate flora in pregnancy and
      effect of oral clindamycin.

PMID- 15516420
TI  - ACOG practice bulletin: Clinical management guidelines for obstetrician
      gynecologists, number 57, November 2004. Gynecologic herpes simplex virus
      infections.
AB  - Both herpes simplex virus (HSV) type I and HSV type 2 can cause genital herpes.
      Because the infection is chronic, genital herpes has become the most common
      sexually transmitted disease among women. The prevalence of the HSV-2 antibody
      among women in the United States is 26%, although genital herpes has been
      diagnosed in only a small proportion (10-25%) of individuals with HSV-2
      antibodies. Herpes simplex virus type I is becoming a more frequent cause of
      genital herpes, especially among young women. Overall,HSV-I seroprevalence in the
      United States is estimated at 67%, although sero-logic data do not provide
      information about site of infection. Recent advances in diagnostic methods and
      therapeutic options are likely to change the management of genital herpes.

PMID- 15516421
TI  - ACOG committee opinion number 304, November 2004. Prenatal and perinatal human
      immunodeficiency virus testing: expanded recommendations.
AB  - Early identification and treatment of all pregnant women with human
      immunodeficiency virus (HIV) is the best way to prevent neonatal disease.
      Pregnant women universally should be tested for HIV infection with patient
      notification as part of the routine battery of prenatal blood tests unless they
      decline the test (ie, opt-out approach). Repeat testing in the third trimester
      and rapid HIV testing at labor and delivery are additional strategies to further
      reduce the rate of perinatal HIV transmission. The Committee on Obstetric
      Practice makes the following recommendations: follow an opt-out prenatal HIV
      testing approach where legally possible; repeat offer of HIV testing in the third
      trimester to women in areas with high HIV prevalence, women known to be at high
      risk for HIV infection, and women who declined testing earlier in pregnancy, as
      allowed by state laws and regulations; use conventional HIV testing for women who
      are candidates for third-trimester testing; use rapid HIV testing in labor for
      women with undocumented HIV status; and if a rapid HIV test result is positive,
      initiate antiretroviral prophylaxis (with consent) without waiting for the
      results of the confirmatory test.

PMID- 15516422
TI  - ACOG committee opinion number 305, November 2004. Influenza vaccination and
      treatment during pregnancy.
AB  - Influenza vaccination is an essential element of prenatal care. The American
      College of Obstetricians and Gynecologists' Committee on Obstetric Practice
      supports the Centers for Disease Control and Prevention's expanded recommendation
      that women who will be pregnant during the influenza season (October through mid
      May) should be vaccinated. The ideal time to administer the vaccine is October
      and November; however, it is appropriate to vaccinate patients throughout the
      influenza season as long as the vaccine supply lasts. This intramuscular
      inactivated vaccine may be used in all 3 trimesters. Because of the unknown
      effects of influenza antiviral drugs on pregnant women and their fetuses, the
      Committee on Obstetric Practice recommends that these antiviral agents should be
      used during pregnancy only if the potential benefits justify the potential risks.

PMID- 15516423
TI  - Cervical cancer complicating pregnancy: two patients with three clinical
      objectives.

PMID- 15516424
TI  - Conservative treatment of stage IA2 squamous cell carcinoma of the cervix during
      pregnancy.
AB  - BACKGROUND: The standard management of early-stage invasive cervical cancer in
      early pregnancy is radical hysterectomy with the fetus in situ. We describe a
      case of early invasive cervical cancer in pregnancy that was treated with a
      conservative surgical approach. CASE: A nulliparous pregnant women at 15 weeks of
      gestation was diagnosed with stage IA2 invasive cervical cancer. She declined a
      radical hysterectomy, desiring to continue the pregnancy. A repeat cervical
      conization with retroperitoneal lymph node dissection was followed by radical
      trachelectomy 6 weeks after delivery. Currently she has 2 children, and there is
      no evidence of recurrence. CONCLUSION: Conservative stepwise surgical management
      of early invasive cervical cancer in the first half of pregnancy was a feasible
      approach in this woman who wished to continue the pregnancy.

PMID- 15516425
TI  - Actinomyces: normal flora or pathogen?

PMID- 15516426
TI  - Retroperitoneal fibrosis secondary to actinomycosis with no intrauterine device.
AB  - BACKGROUND: Actinomycotic pelvic infection usually occurs in the presence of an
      intrauterine device. It can result in pelvic inflammatory disease, tubo-ovarian
      abscess, and retroperitoneal fibrosis. CASE: A 35-year-old multipara who had
      never used an intrauterine device presented with a 5-month history of
      progressively worsening, colicky, right-sided abdominal pain, dysuria, weight
      loss, and constipation. She was found to have retroperitoneal fibrosis. The
      diagnosis of actinomycotic pelvic infection was made at laparotomy. CONCLUSION:
      Actinomycosis may be considered in the differential diagnosis of women with
      retroperitoneal fibrosis, even when there is no history of an intrauterine
      device.

PMID- 15516427
TI  - Massive fetal ascites causing increased middle cerebral artery systolic velocity.
AB  - BACKGROUND: An elevated peak systolic velocity in the middle cerebral artery,
      assessed by Doppler ultrasonography, is commonly associated with fetal anemia.
      Other fetal abnormalities associated with a high middle cerebral artery velocity
      have rarely been reported. CASE: A fetus with increasing ascites was found to
      have an elevated middle cerebral artery peak systolic velocity. Following
      paracentesis, the peak systolic velocity normalized. Peak systolic velocity
      continued to correlate with the level of ascites, falling to normal ranges when
      large-volume amniocentesis and paracentesis were performed. At birth, the infant
      was found to have a normal hematocrit. CONCLUSION: An elevated middle cerebral
      artery peak systolic velocity may result from massive fetal ascites without
      anemia. We hypothesize that the massive ascites led to increased afterload of the
      heart, with relatively preserved preload, leading to an increased systolic blood
      pressure and an elevated middle cerebral artery peak systolic velocity.

PMID- 15516428
TI  - Pregnancy and delivery after right common carotid artery endarterectomy.
AB  - BACKGROUND: Carotid artery atherosclerosis and essential hypercholesterolemia can
      add a predisposing risk factor for coagulation in pregnancy. Careful management
      of anticoagulation during labor, delivery, and puerperium is called for in such a
      case. CASE: A 41-year-old woman, gravida 2, para 1, with a previous
      endarterectomy at the right common carotid artery because of atherosclerotic
      plaques, underwent anticoagulation studies and prophylactic antithrombotic
      therapy. Low-molecular-weight heparin was administrated during pregnancy and
      puerperium. She successfully delivered by cesarean at 36 weeks of gestation.
      CONCLUSION: Low-molecular-weight heparin treatment is an effective and safe
      therapy in pregnancy. The healthy course of therapy, delivery, and puerperium
      reported here is a reference that may support women with a similar history.

PMID- 15516429
TI  - A fatal case of Clostridium sordellii septic shock syndrome associated with
      medical abortion.
AB  - BACKGROUND: Clostridia bacteria are infrequent human pathogens. In the obstetric
      and gynecologic literature, Clostridium sordellii infections have been very
      rarely reported. This is a case of infection following medical termination of
      early pregnancy with mifepristone and misoprostol. CASE: A 27-year-old woman
      presented for termination of pregnancy at 5.5 weeks from her last menstrual
      period. She received mifepristone 200 mg orally followed by 800 microg vaginal
      misoprostol. Three days after administration of misoprostol, she complained of
      dizziness, pelvic pain, and bleeding. The next day, she experienced worsening of
      symptoms and was hospitalized. She developed pulmonary edema, ascites, and heart
      failure. Despite supportive measures, antibiotics, and hysterectomy, she died 3
      days later. The post mortem examinations indicated that death was caused by shock
      secondary to C sordellii infection. CONCLUSION: The frequency of infection
      following medical abortion is low. The rapid and fatal course of this infection
      is similar to other obstetric and gynecologic cases reported in the literature.
      Although providers should remain vigilant to the possibility of infection
      following medical abortion, the overall proven safety of medical abortion remains
      the same.

PMID- 15516430
TI  - Amyloidosis of the endometrium: an asymptomatic presentation.
AB  - BACKGROUND: Amyloidosis of the endometrium is a rare occurrence according to
      current literature. Previously reported cases have presented with menorrhagia or
      postmenopausal bleeding. CASE: A postmenopausal woman with multiple medical
      problems presented with fatigue and weight loss. During the evaluation for her 18
      kg weight loss, a computed tomography scan revealed an enlarged uterus and liver
      lesions. Endometrial and liver biopsies were performed secondary to concern over
      metastatic cancer, given an enlarged uterus in a postmenopausal woman with liver
      masses. She was found to have systemic primary amyloidosis in multiple organs,
      including her endometrium. CONCLUSION: This patient represents an interesting
      case of systemic amyloidosis involving the endometrium that is not associated
      with vaginal bleeding. The presence of amyloid in the endometrium may be more
      common than currently recognized, because patients without vaginal bleeding are
      not routinely evaluated for amyloid deposition in their reproductive organs.

PMID- 15516431
TI  - Low-grade endometrial stromal sarcoma arising from sciatic nerve endometriosis.
AB  - BACKGROUND: Endometrial stromal sarcoma arising from extrauterine endometriosis
      is a rare and not easily diagnosed tumor. We present a case arising from sciatic
      nerve endometriosis in a 50-year-old woman. CASE: The patient had a long history
      of endometriosis and presented with a left buttock mass and motor deficit.
      Magnetic resonance imaging showed a large tumor of the sciatic nerve with pelvic
      extension. She underwent total hysterectomy, bilateral salpingo-oophorectomy, and
      excision of pelvic endometriotic pockets, allowing the diagnosis of low-grade
      endometrial stromal sarcoma arising from endometriosis. She received systemic
      chemotherapy, gonadotropin-releasing hormone agonist therapy, and palliative
      radiation therapy, but her disease progressed. CONCLUSION: Aggressive
      endometriosis raises important diagnostic and therapeutic difficulties and may
      correspond to misdiagnosed rare malignant neoplasms, which should be treated.

PMID- 15516432
TI  - Symptomatic diaphragmatic endometriosis ten years after total abdominal
      hysterectomy.
AB  - BACKGROUND: Endometriosis is a disease that affects women, mostly in the age
      range of 25-35 years, and in most cases pelvic organs are involved. Involvement
      of the diaphragm after hysterectomy is extremely uncommon. CASE: A 50-year-old
      woman presented to our department with right upper-quadrant abdominal pain. Ten
      years before her admission, she underwent total hysterectomy and right salpingo
      oophorectomy for a large leiomyomatous uterus. On evaluation, a right
      diaphragmatic lesion was identified by computed tomography. An explorative
      laparotomy was then performed, which revealed a 4-cm diaphragmatic cyst
      compressing the liver surface and containing thick chocolate-colored material.
      The lesion was totally excised. Pathological examination confirmed the diagnosis
      of endometriotic cyst. CONCLUSION: The diagnosis of endometriosis involving the
      diaphragm with no evidence of disease in the pelvis 10 years after hysterectomy,
      although a rare situation, should be considered in the differential diagnosis of
      a symptomatic diaphragmatic lesion in a woman with a single functioning ovary.

PMID- 15516433
TI  - Hepatic ischemia associated with coarctation of the aorta in pregnancy: key
      issues in differential diagnosis.
AB  - BACKGROUND: Hepatic ischemia associated with coarctation of the aorta has not
      previously been reported in an adult; pregnancy increases the pressure gradient
      across a coarctation. CASE: A young woman with known coarctation of the aorta
      developed severe hepatic ischemia in pregnancy. A pregnancy-induced increase in
      the mean pressure gradient across the coarctation, from 18 mm Hg before pregnancy
      to 40 mm Hg in the third trimester, predisposed to critical hepatic hypoperfusion
      in the setting of dehydration. CONCLUSION: This case documents an association
      between coarctation of the aorta and hepatic ischemia, precipitated by pregnancy
      and dehydration in combination. It emphasizes the need in the assessment of
      patients with liver disease in pregnancy to consider not only "traditional"
      pregnancy-related conditions such as acute fatty liver and the hemolysis,
      elevated liver enzymes, low platelets syndrome, in which delivery may be
      necessary as a clinical emergency, but also those in which the circulatory and
      metabolic demands of pregnancy may precipitate liver injury.

PMID- 15516434
TI  - Fetal femur fracture and external cephalic version.
AB  - BACKGROUND: Femoral fractures due to birth trauma are extremely rare. External
      cephalic version is considered a relatively safe alternative when dealing with
      breech presentation, but it can be associated with complications. CASE: This
      patient underwent elective cephalic version for breech presentation at 36 weeks
      of gestation. Due to concerns of fetal distress after the version, a cesarean
      delivery was performed. The newborn had a bruised leg at delivery, and X-ray
      studies confirmed a distal femoral corner fracture. CONCLUSION: This case
      demonstrates another risk of external cephalic version. Physicians and patients
      should be aware of this potential complication.

PMID- 15516435
TI  - Prenatal ultrasound diagnosis of poland syndrome.
AB  - BACKGROUND: Poland syndrome is a congenital nongenetic anomaly characterized by
      unilateral chest wall hypoplasia, ipsilateral hand abnormalities, and
      hemivertebrae. It has not ben described so far in the fetus. CASE: The patient
      was referred for suspected left-arm hypomelia at 22 weeks of gestation. On
      ultrasonography, we confirmed the presence of severe left-sided hypomelia and
      detected an asymmetry of the rib cage and 3 thoracic hemivertebrae. The absence
      of heart defects led us to make the putative diagnosis of Poland syndrome. After
      termination of pregnancy, the diagnosis was confirmed by the pathologist.
      CONCLUSION: The possibility of diagnosing Poland syndrome in utero is important
      for proper management and counseling. If the syndrome is suspected in a fetus,
      counselors may refer to specific postnatal data to provide the couple with
      survival rates, treatment options, and results and morbidity figures. If the
      pregnancy is terminated, a detailed necropsy is warranted to confirm the
      diagnosis because familial transmission has been reported.

PMID- 15516436
TI  - Buttock necrosis after uterine artery embolization.
AB  - BACKGROUND: Uterine artery embolization is an increasingly popular alternative to
      hysterectomy or myomectomy for treatment of symptomatic uterine leiomyomata.
      CASE: A woman with a symptomatic uterine fibroid developed 2 areas of full
      thickness necrosis on her right buttock following uterine artery embolization.
      After surgical debridement, healing occurred over 14 weeks. CONCLUSION: Buttock
      necrosis is a possible complication of nontarget embolization during uterine
      artery embolization.

PMID- 15516437
TI  - Necrotic leiomyoma and gram-negative sepsis eight weeks after uterine artery
      embolization.
AB  - BACKGROUND: Uterine artery embolization for symptomatic leiomyomata is generally
      safe, but rare life-threatening complications, including sepsis, can result.
      CASE: A 39-year-old woman with primary antiphospholipid syndrome, who was on
      chronic warfarin therapy, underwent uterine artery embolization for severe
      menorrhagia and a 12-cm intracavitary leiomyoma. Eight weeks postembolization,
      the patient, who had been essentially asymptomatic, presented in septic shock
      from gram-negative anaerobic bacteria. She underwent hysterectomy and bilateral
      salpingo-oophorectomy for a large infarcted necrotic leiomyoma and partial
      uterine necrosis. The patient's 8-day hospitalization required extended care in
      the intensive care unit and blood transfusion and resulted in surgical menopause
      in a patient who is not a candidate for hormone therapy. CONCLUSION: Uterine
      artery embolization is a procedure not without significant risks. From published
      case reports, it appears that patients most at risk for severe infection of an
      infarcted leiomyoma after this procedure are those with a large dominant
      leiomyoma.

PMID- 15516438
TI  - Rectovaginal fistula repair using a porcine dermal graft.
AB  - BACKGROUND: Rectovaginal fistula repair is commonly performed through a vaginal
      route. In many cases, healthy tissue such as an autologous fat pad may be
      interposed between the suture lines and the vaginal epithelium to facilitate
      healing and prevent recurrence. We present a simple alternative to autologous
      flaps with the use of porcine dermal grafts in the repair of rectovaginal
      fistulae. CASES: Two patients are presented with rectovaginal fistulae. In both
      cases the patients were found to have insufficient native tissue to achieve an
      adequate traditional multilayered closure, and therefore an acellular collagen
      porcine dermal graft was used as an interposition graft between the rectum and
      the vaginal epithelium in the repair. CONCLUSION: Porcine dermal grafts may be a
      viable alternative to traditional autologous flaps or human dermal grafts for the
      repair of rectovaginal fistula.

PMID- 15516439
TI  - Port-site implantation after laparoscopic treatment of borderline ovarian tumors.
AB  - BACKGROUND: The aim of this article is to report 3 cases of port-site
      implantation after laparoscopic treatment of a borderline ovarian tumor. CASES:
      Three patients underwent a laparoscopic procedure for a serous (2 patients) or
      mucinous (1 patient) borderline ovarian tumor. In 2 patients, the port-site
      implantation was discovered during a later surgical procedure, and one was
      discovered clinically 11 months after the initial laparoscopic oophorectomy.
      Surgical resection of the port-site was the only treatment in all cases. These
      women are currently alive and disease-free 11, 23, and 51 months after the
      treatment of the scar metastasis. CONCLUSIONS: These results suggest that, unlike
      port-site metastasis in other gynecologic malignancies, the prognosis in patients
      with a port-site implantation after laparoscopic management of borderline ovarian
      tumor is excellent. The treatment of this complication is surgical resection.

PMID- 15516440
TI  - Early abdominal incision recurrence in a patient with stage I adenocarcinoma of
      the endometrium.
AB  - BACKGROUND: Although most patients with a surgical stage I endometrial cancer
      have an excellent prognosis, some patients will experience a recurrence.
      Endometrial cancer typically recurs at the vaginal cuff or in the pelvis;
      however, it can recur distantly in the abdomen or lung. Although recurrences have
      been reported at laparoscopic trochar sites, it is unusual to have a recurrence
      in the abdominal incision after laparotomy. CASE: A 51-year-old woman was
      diagnosed with stage Ib grade 2 adenocarcinoma of the endometrium and stage IV
      endometriosis. Six months after surgery, she presented with a mass in the lateral
      aspect of her Maylard incision. Computed tomography scans of the chest, abdomen,
      and pelvis showed no evidence of recurrent disease. The mass was resected and
      confirmed to be an adenocarcinoma similar to the endometrial primary. CONCLUSION:
      This case is interesting because of the rapid recurrence of the endometrial
      primary at an unusual site-the abdominal incision. It illustrates the need to
      carefully evaluate all suspicious masses, even as early as 6 months after
      diagnosis and surgical staging.

PMID- 15516441
TI  - Trophoblastic tissue spread to the sigmoid colon after uterine perforation.
AB  - BACKGROUND: Trophoblastic tissue spread following uterine perforation during
      dilation and curettage is rare. We present a case of trophoblastic spread to the
      sigmoid colon following uterine perforation, which was treated by surgical
      removal of the implants and intramuscular administration of methotrexate. CASE: A
      woman presented 3 weeks after curettage for a blighted ovum. Laparotomy performed
      for suspected intra-abdominal bleeding revealed bleeding trophoblastic implants
      in a perforation tract and the anterior uterine wall and on the appendix
      epiploica of the sigmoid colon. The implants were surgically removed and
      methotrexate was administered for persistently high beta-hCG levels. The patient
      fully recovered. CONCLUSION: Extrauterine trophoblastic implants should be
      considered in women evaluated for abdominal pain whose pregnancy test is positive
      after uterine perforation. Conservative treatment with methotrexate in nonacute
      patients may be considered.

PMID- 15516442
TI  - Paraneoplastic limbic encephalitis: ovarian cancer presenting as an amnesic
      syndrome.
AB  - BACKGROUND: Paraneoplastic limbic encephalitis (PLE) is a rare neurologic
      manifestation of malignancy. Paraneoplastic limbic encephalitis typically
      presents with short-term memory loss, seizures, or other limbic system
      abnormalities. The majority of PLE cases are associated with lung and testicular
      cancer. CASE: We present the first case of PLE attributable to an epithelial
      ovarian cancer. The 58-year-old woman presented with rapidly progressing short
      term memory loss and amnesia. The diagnosis of ovarian cancer was suspected on
      the basis of computed tomography scan findings. The patient showed dramatic
      clinical improvement within 2 weeks of debulking surgery and after the initiation
      of plasmapheresis and chemotherapy. CONCLUSION: Paraneoplastic limbic
      encephalitis is a rare complication of ovarian tumors that is potentially
      reversible with prompt surgical management of the primary tumor, plasmapheresis,
      and chemotherapy.

PMID- 15516443
TI  - Coccidioidomycosis mimicking ovarian cancer.
AB  - BACKGROUND: Dissemination of coccidioidomycosis to the abdominal cavity is rare.
      No previous case of peritoneal coccidioidomycosis has presented as an adnexal
      mass. CASE: We report a case of peritoneal coccidioidomycosis mimicking ovarian
      carcinoma. The patient presented with a complex ovarian mass, ascites, omental
      caking, and an elevated CA 125. The ultimate diagnosis was not made until frozen
      section histopathology was performed at staging laparotomy. CONCLUSION:
      Peritoneal coccidioidomycosis can present with the clinical, radiographic, and
      serologic features of ovarian cancer. Although essential for diagnosis and
      staging, radiographic studies and tumor markers have limited specificity.
      Coccidioidomycosis now joins other benign conditions that comprise the
      differential diagnosis of patients who present with what seems to be advanced
      ovarian carcinoma. Infectious diseases consultation is recommended for the
      management of peritoneal coccidioidomycosis.

PMID- 15516444
TI  - Abdominal compartment syndrome secondary to ovarian mucinous cystadenoma.
AB  - BACKGROUND: Abdominal compartment syndrome secondary to a very large benign
      ovarian tumor has been rarely reported in gynecology. With the increase of
      intraabdominal pressure in abdominal compartment syndrome, all major organ
      systems are adversely affected, causing a potentially fatal condition. CASE: A 43
      year-old woman presenting with a tensely distended abdomen developed hypotension,
      difficulty in ventilation, and anuria. An ovarian tumor complicated by abdominal
      compartment syndrome was diagnosed, along with hemodynamic decompensation. Prompt
      resuscitation with immediate surgical removal of the tumor reversed the life
      threatening situation. CONCLUSION: Timely aggressive resuscitation, prompt
      surgical decompression, and intensive perioperative hemodynamic management are
      required for patients with ovarian mucinous cystadenoma complicated by abdominal
      compartment syndrome.

PMID- 15516445
TI  - Treatment of endometrial stromal sarcoma with a gonadotropin-releasing hormone
      analogue.
AB  - BACKGROUND: Endometrial stromal sarcoma can present management difficulties due
      to its lack of response to conventional chemotherapy and radiotherapy. Various
      hormonal therapies have been shown to reduce tumor volume in both primary and
      recurrent disease. CASE: A woman who underwent myomectomy was discovered to have
      a low-grade endometrial stromal sarcoma. Treatment with the gonadotropin
      releasing hormone (GnRH) analogue triptorelin before surgery had produced
      reduction in uterine size. The woman developed tumor recurrence six months after
      definitive surgical treatment. The tumor enlarged rapidly during a 2-month
      period, with development of a right-sided hydronephrosis. Repeat administration
      of triptorelin was accompanied by resolution of the hydronephrosis and reduction
      in tumor volume. Biopsy results confirmed recurrent low-grade endometrial stromal
      sarcoma with moderate estrogen and progesterone receptor positivity. CONCLUSION:
      Control of progression of a recurrent endometrial stromal sarcoma was achieved
      with the GnRH analogue triptorelin. This is the first report in the English
      language literature during a 30-year period of single-agent GnRH analogue being
      an effective treatment intervention in this context.

PMID- 15516446
TI  - Hemolytic uremic syndrome presenting after treatment of endodermal sinus tumor.
AB  - BACKGROUND: Hemolytic uremic syndrome is a rare multisystem disorder that is
      caused by infections, preeclampsia, autoimmune disorders, or oral contraceptive
      agents, and rarely in association with different cancers and chemotherapeutic
      agents. CASE: A 34-year-old woman who presented for evaluation of a pelvic mass
      received a diagnosis of International Federation of Gynecology and Obstetrics
      (FIGO) stage 1c endodermal sinus tumor at laparotomy. Three months after
      receiving 3 courses of bleomycin, etoposide, and cisplatinum, she presented with
      renal failure, thrombocytopenia, anemia, and severe hypertension. Cancer
      associated hemolytic uremic syndrome was diagnosed, and the patient was treated
      with plasmaphoresis, blood transfusion, and hemodialysis. CONCLUSION: Cancer
      associated hemolytic uremic syndrome has a high mortality rate; thus, prompt
      diagnosis is critical to survival.

PMID- 15516447
TI  - Protrusio acetabuli presenting as a complex pelvic mass after total hip
      arthroplasty.
AB  - BACKGROUND: The differential diagnosis in an elderly woman with a complex pelvic
      mass includes benign and malignant diseases. CASE: A woman in her ninth decade
      was discovered to have both a breast mass and a pelvic mass at examination. After
      diagnostic breast biopsy results that confirmed invasive breast carcinoma, pelvic
      examination and ultrasonography were performed. The ultrasonogram demonstrated a
      large complex pelvic mass. The patient underwent an exploratory laparotomy at the
      time of her mastectomy. The pelvic mass was a protrusio acetabuli resulting from
      a prior right total hip arthroplasty. CONCLUSION: A complex pelvic mass secondary
      to protrusio acetabuli is a rare clinical finding.

PMID- 15516448
TI  - Delayed hemorrhage after cervical conization unmasking severe factor XI
      deficiency.
AB  - BACKGROUND: Factor XI deficiency, a rare bleeding disorder found most commonly in
      patients of Ashkenazi Jewish background, may be present in patients with a
      history of abnormal bleeding after elective surgery. CASE: A patient of Ashkenazi
      Jewish descent presented 12 days after cervical conization for adenocarcinoma in
      situ with severe vaginal bleeding requiring multiple transfusions and uterine
      artery embolization. After a thorough workup, a severe factor XI deficiency was
      found. The patient ultimately required modified radical hysterectomy for
      treatment of early cervical cancer. With appropriate perioperative management,
      the patient underwent abdominal surgery without further bleeding complications.
      CONCLUSION: Factor XI deficiency can present with severe bleeding episodes after
      elective surgery. Adequate preoperative assessment and perioperative management
      are necessary to prevent bleeding complications in these patients.

PMID- 15516449
TI  - Interstitial pregnancy and transcervical curettage.
AB  - BACKGROUND: Interstitial pregnancies too large to be treated with methotrexate
      are usually managed surgically, and that may adversely affect future fertility
      and pregnancies. Transcervical curettage under laparoscopic guidance may be
      possible in some cases if the pregnancy is accessible vaginally. CASE: Three
      women with interstitial pregnancy were treated by transcervical suction curettage
      under laparoscopic guidance. In all cases, the procedure was quick, bleeding was
      minimal, and there were no complications. Removal was complete, and the serum
      beta-hCG quickly became undetectable. CONCLUSION: Transcervical curettage under
      laparoscopic guidance provides an alternative conservative treatment for
      interstitial pregnancy.

PMID- 15516450
TI  - Heterotopic pregnancy in a natural conception cycle presenting as hematometra.
AB  - BACKGROUND: Heterotopic pregnancy is a rare event in natural conception cycles.
      Diagnosis of heterotopic pregnancy requires a high index of suspicion. Described
      herein is a reported case of a heterotopic pregnancy presenting as hematometra.
      CASE: A young, multiparous woman, with her last menstrual period 6 weeks before
      presentation, complained of a dark reddish-brown vaginal discharge and
      progressive left lower-quadrant discomfort during early pregnancy following a
      natural conception cycle. An intrauterine mass was observed, and subsequently a
      heterotopic pregnancy complicated by hematometra was diagnosed with the help of
      transvaginal ultrasonography and 3-dimensional power Doppler ultrasound
      angiography. CONCLUSION: Women with intrauterine fluid accumulation during
      pregnancy may be at risk for coexistent ectopic pregnancy. High resolution
      transvaginal color Doppler sonography may be useful to identify a heterotopic
      pregnancy preoperatively.

PMID- 15516451
TI  - Tuboovarian abscess: a postoperative complication of endometrial ablation.
AB  - BACKGROUND: Global endometrial ablation may be associated with serious
      complications. CASE: We present a case of bilateral tuboovarian abscesses that
      developed 50 days postoperatively after a thermal ablation. The patient underwent
      total abdominal hysterectomy and bilateral salpingo-oophorectomy. CONCLUSION:
      Infectious morbidity is known to occur after thermal endometrial ablation.
      Further investigation is required into ways of reducing the risks of endometrial
      ablation.

PMID- 15516452
TI  - Surgical management of vaginal vault prolapse in a woman with a neovagina and
      pelvic kidneys.
AB  - BACKGROUND: Women with Mayer-Rokitansky-Kuster-Hauser syndrome have congenital
      absence of the uterus and upper two-thirds of the vagina, which is frequently
      accompanied by skeletal and renal anomalies. Mechanical dilation or surgical
      creation of a vagina allows for function but does not provide endopelvic fascial
      support of the vagina. Vaginal prolapse may occur. CASE: A 32-year-old woman
      presented with pelvic kidneys and a 5-year history of prolapse of her
      mechanically created neovagina. She underwent a sacrospinous ligament suspension
      with a cadaveric fascia lata bridge. The apex of the neovagina was 5 cm above the
      hymen 30 months postoperatively. CONCLUSION: An allograft colpopexy to the
      sacrospinous ligament is an effective method of surgical treatment of women with
      a prolapsed shortened vagina and an inaccessible presacral space.

PMID- 15516453
TI  - Milk-alkali syndrome in pregnancy.
AB  - BACKGROUND: Severe hypercalcemia, a potentially life-threatening medical
      emergency, is rare in pregnancy. CASE: We report a 32-year-old woman presenting
      early in the second trimester with severe hypercalcemia (total calcium 22 mg/dL),
      alkalosis, and acute renal insufficiency resulting from excessive ingestion of
      calcium carbonate-containing antacid for gastroesophageal reflux. The patient was
      treated with aggressive hydration and furosemide, and received 1 dose of
      intravenous etidronate, leading to short-term symptomatic hypocalcemia. To our
      knowledge, this is the third reported case of milk-alkali syndrome in pregnancy.
      CONCLUSION: Milk-alkali syndrome is an uncommon cause of hypercalcemia in
      pregnancy. Intravenous hydration with saline should be the cornerstone of
      treatment, reserving bisphosphonates for selected cases.

PMID- 15516454
TI  - Obstetric management of Klippel-Trenaunay syndrome.
AB  - BACKGROUND: Klippel-Trenaunay syndrome is a rare congenital disease characterized
      by extensive cutaneous vascular malformations, venous varicosities, focal
      abnormalities of the deep venous system, and underlying soft tissue or bony
      hypertrophy. Given the rarity of the disease, there is little information
      available to counsel patients with Klippel-Trenaunay syndrome regarding obstetric
      outcome. CASES: We report our experience with 3 patients in whom Klippel
      Trenaunay syndrome complicated 4 pregnancies. Successful delivery of a healthy
      infant at or beyond 36 weeks of gestation was achieved in all pregnancies. One of
      the 4 pregnancies was complicated by pulmonary embolism. CONCLUSION: Klippel
      Trenaunay syndrome was once thought to be a contraindication to pregnancy. With
      careful management, successful pregnancies can be achieved.

PMID- 15516455
TI  - Detection of fetal lactate with two-dimensional-localized proton magnetic
      resonance spectroscopy.
AB  - BACKGROUND: Antenatal surveillance is inefficient for accurately detecting fetal
      compromise. A noninvasive technique for assessing fetal metabolic status would be
      useful for clinical management. CASE: Fetal magnetic resonance spectroscopy was
      performed at 20 weeks in a pregnancy complicated by severe intrauterine growth
      restriction to determine if lactate, a metabolite associated with fetal hypoxia,
      was present. Two-dimensional, single-slice proton magnetic resonance spectroscopy
      was carried out at 1.5 T using a volume-selective, double-spin echo technique.
      Lactate was detected in fetal back muscle. Fetal death occurred the next day.
      CONCLUSIONS: Although this initial report is purely experimental, further
      development of this technique may prove to be a valuable noninvasive tool in the
      management of suspected fetal hypoxia.

PMID- 15516456
TI  - Repair of uterine dehiscence with continuation of pregnancy.
AB  - BACKGROUND: Uterine dehiscence in the past has been treated with delivery of the
      pregnancy and repair of the uterus or cesarean hysterectomy. Uterine repair and
      continuation of the pregnancy has not been attempted to our knowledge. CASE: A
      patient with a history of a laparoscopic myomectomy presented at 28 weeks of
      gestation with a uterine dehiscence. This was repaired and the pregnancy
      continued until fetal lung maturity at 34 weeks. CONCLUSION: Repair of a uterine
      dehiscence in a hemodynamically stable patient and continuation of the pregnancy
      should be considered in a very premature pregnancy to improve neonatal outcome.

PMID- 15516457
TI  - Management of maternal cor triatriatum during pregnancy.
AB  - BACKGROUND: Cor triatriatum is a rare congenital cardiac abnormality, usually
      diagnosed in childhood. We describe the first case of atrial fibrillation
      secondary to maternal cor triatriatum diagnosed during the first trimester of
      pregnancy and its successful management until postpartum (MEDLINE [1966 to 2003]
      and Embase [1988 to 2003], using MeSH terms for "cor triatriatum" and
      "pregnancy"). CASE: A 31-year-old gravida 1 complained of progressive dyspnea on
      exertion and palpitations, which occurred at the end of the first trimester of
      the pregnancy. Atrial fibrillation was observed on electrocardiogram. A
      transesophageal echocardiography examination revealed a cor triatriatum that was
      responsible for the arrhythmia. beta-adrenergic blocking agents and digitalis
      glycosides were used to control supraventricular arrhythmia, while low-molecular
      weight heparin was administered to prevent thromboembolic events. Low-molecular
      weight heparin was discontinued at 37 weeks of gestation, and subcutaneous
      unfractionated heparin was administered instead. Pregnancy continued a normal
      course until full-term vaginal delivery with epidural anesthesia and close
      hemodynamic monitoring. CONCLUSION: A standard treatment for atrial fibrillation
      could be effective in preventing maternal hemodynamic complications secondary to
      cor triatriatum during pregnancy. Moreover, this case illustrates the American
      consensus in neuraxial anesthesia and anticoagulation, which supports the opinion
      that there is a limited risk associated with the use of epidural and spinal
      anesthesia in the presence of subcutaneous heparin treatment.

PMID- 15516458
TI  - Peak expiratory flow (PEF) monitoring.

PMID- 15516459
TI  - Difficult bacteria, antibiotic resistance and transmissibility in cystic
      fibrosis.

PMID- 15516460
TI  - Unravelling salt transport in cystic fibrosis.

PMID- 15516461
TI  - Identifying failure of empirical treatment for pneumonia: vigilance and common
      sense.

PMID- 15516462
TI  - What happens to patients with respiratory disease when they fly?

PMID- 15516463
TI  - Tuberculosis and anti-TNF-alpha treatment.

PMID- 15516464
TI  - When can personal best peak flow be determined for asthma action plans?
AB  - BACKGROUND: Written asthma action plans based on personal best peak expiratory
      flow (PEF) consistently improve health outcomes, whereas those based on predicted
      PEF do not. Guidelines state that personal best PEF should be assessed over 2-3
      weeks during good asthma control, but it is unclear how long to wait after
      commencing or changing treatment. METHODS: Electronically recorded spirometric
      data from 61 subjects with initially poorly controlled asthma from a 72 week
      budesonide study were analysed. For each week, average morning pre-bronchodilator
      PEF was calculated and personal best PEF was determined as the highest PEF in the
      previous 2 weeks. The time to plateau was defined as the week beyond which no
      further improvement occurred. RESULTS: At baseline, average morning PEF was 61%
      predicted and personal best PEF was 87% predicted. Personal best PEF from twice
      daily monitoring increased to a plateau of 95% predicted (p<0.0001) after only 3
      weeks of budesonide treatment. However, average morning PEF continued to improve
      for 3 months and "as needed" reliever use for 7 months. CONCLUSIONS: Personal
      best PEF is a useful concept for asthma self-management plans when determined as
      the highest PEF over the previous 2 weeks. With twice daily monitoring, personal
      best PEF reaches plateau levels after only a few weeks of corticosteroid
      treatment.

PMID- 15516465
TI  - Childhood factors associated with asthma remission after 30 year follow up.
AB  - BACKGROUND: Factors contributing to either "complete" or "clinical" remission of
      asthma are important to know since there is no cure for the disease. METHODS: A
      cohort of 119 allergic asthmatic children was examined three times with a mean
      follow up of 30 years. They were aged 5-14 years at visit 1 (1966-9), 21-33 years
      at visit 2 (1983-6), and 32-42 years at visit 3 (1995-6). Complete remission of
      asthma at visit 3 was defined as no asthma symptoms, no use of inhaled
      corticosteroids, normal lung function (FEV1 >90% predicted), and no bronchial
      hyperresponsiveness (PC10 >16 mg/ml). Clinical remission was defined as no asthma
      symptoms and no use of inhaled corticosteroids. RESULTS: 22% of the group was in
      complete remission of asthma at visit 3 and a further 30% was in clinical
      remission (total 52%); 57% of subjects in clinical remission had bronchial
      hyperresponsiveness and/or a low lung function. Logistic regression analyses
      showed that a higher FEV1 in childhood and more improvement in FEV1 from age 5-14
      to 21-33 were associated with both complete and clinical asthma remission at age
      32-42. CONCLUSIONS: Complete remission of asthma was present in a small subset of
      asthmatics while half the subjects showed clinical remission. Both complete and
      clinical remission were associated with a higher lung function level in childhood
      and a higher subsequent increase in FEV1. These results support the view that
      defining remission only on the basis of symptoms and medication use will overlook
      subjects with subclinical active disease and possibly associated airway
      remodelling.

PMID- 15516466
TI  - Psychological factors and asthma quality of life: a population based study.
AB  - BACKGROUND: Reports of psychological conditions in asthmatic subjects have been
      limited to certain population groups or convenience samples. A study was
      undertaken of the prevalence of psychological distress in asthma in the general
      population and its associations with quality of life. METHODS: The WANTS Health
      and Well-being Survey is a population household interview survey of adults (age >
      or =18) in Western Australia, the Northern Territory, and South Australia. Data
      obtained were weighted to the closest census data to provide population
      representative estimates. Positive answers to two questions: "Have you ever been
      told by a doctor that you have asthma?" and "Do you still have asthma?"
      determined current doctor-diagnosed asthma. Other items included the SF-12, the
      Kessler-10 index of psychological distress, questions on feelings of lack of
      control in different areas of life, and on mental health conditions. RESULTS:
      From the available sample of 10 080, 7619 interviews were completed
      (participation rate 74.8%), with 834 people reporting current doctor-diagnosed
      asthma (11.2%). Psychological distress was more frequent in those with asthma
      (17.9% v 12.2%, p<0.01) and a higher proportion with asthma were at higher risk
      for anxiety or depression (40.5% v 31.2%, p<0.01). Mental health conditions were
      also more common (16.2% v 10.8%, p<0.01), as was the frequency of those who
      sometimes or always felt a lack of control over their health (33.5% v 24.3%,
      p<0.01). People with both asthma and psychological distress had significantly
      lower scores on the SF-12 physical component summary (PCS) than those with either
      asthma or distress alone. Among those with psychological distress, mental
      component summary (MCS) scores did not differ between asthmatic and non-asthmatic
      respondents. In a multiple regression model the frequency of a feeling of lack of
      control over health-together with age, family's financial situation, education
      level, and number of days partially unable to work or perform usual duties-was
      significantly associated with scores on the PCS (r = 0.73, adjusted r2 = 0.54).
      CONCLUSION: These results, from a representative population sample, show that
      psychological distress and decreased feelings of control are common in asthma and
      are significantly associated with physical health status.

PMID- 15516467
TI  - Raised cord serum immunoglobulin E increases the risk of allergic sensitisation
      at ages 4 and 10 and asthma at age 10.
AB  - BACKGROUND: Evidence suggests that a raised level of cord serum IgE (CS-IgE) is a
      risk factor for allergic sensitisation. However, whether CS-IgE is a risk for
      asthma is controversial. A study was undertaken to investigate the association
      between CS-IgE levels and allergic sensitisation at 4 and 10 years of age and
      asthma at ages 1-2, 4 and 10. METHODS: CS-IgE was available for 1358 of 1456
      children born between 1989 and 1990. The cohort was evaluated for allergic
      diseases at ages 1, 2, 4 and 10 years. Skin prick tests for six allergens were
      performed on 981 children at age 4 and 1036 at age 10. Asthma was defined based
      on a physician's diagnosis. Using logistic regression analysis, the risk of
      asthma and allergic sensitisation for raised levels of CS-IgE (> or =0.5 kU/l)
      was estimated. RESULTS: At ages 4 and 10 years 20.2% and 27.0% of children,
      respectively, had allergic sensitisation. The risk of allergic sensitisation was
      significantly associated with raised CS-IgE levels at ages 4 (OR 2.29) and 10
      years (OR 1.73). The prevalence of asthma was 10.3% at age 1-2, 15.2% at age 4,
      and 12.8% at age 10. CS-IgE was not associated with asthma at age 1-2 and 4 but
      showed an increased relative risk at age 10 (OR 1.66, 95% CI 1.05 to 2.62). The
      association was stronger in children who did not develop allergic sensitisation
      at age 4 or 10 (OR 3.35, 95% CI 1.41 to 7.93). CONCLUSIONS: Raised cord serum IgE
      is a risk factor for allergic sensitisation at ages 4 and 10 years. This is the
      second study suggesting that CS-IgE is also a risk factor for asthma at age 10,
      probably related to the late onset of asthma. This association is not necessarily
      mediated by allergic sensitisation.

PMID- 15516468
TI  - Use of inhaled corticosteroids following discharge from an emergency department
      for an acute exacerbation of asthma.
AB  - BACKGROUND: Most patients who have an asthma exacerbation leading to a visit to
      an emergency department (ED) will benefit from treatment with inhaled
      corticosteroids (ICS) at discharge. We investigated whether asthmatic children
      and adolescents were receiving ICS after discharge from the ED and identified the
      characteristics of patients and physicians associated with their use. METHODS: A
      cohort of 4042 asthmatic patients aged 5-17 years was selected from the
      administrative database of the Regie de l'assurance maladie du Quebec between
      1997 and 1999. The proportion of patients using ICS 1, 3, and 6 months after ED
      discharge was estimated. Using GEE models the independent contribution of
      sociodemographic variables, markers of asthma severity, prior use of healthcare
      services and ICS, and physician characteristics was investigated on the
      likelihood of using ICS after ED discharge. RESULTS: 68% of children and 51% of
      adolescents had a valid prescription for ICS in the month following discharge. At
      6 months after discharge the corresponding figures were 77% and 60%. The
      strongest predictors of ICS use were age, with adolescents being less likely to
      use ICS than children (OR 0.49; 95% CI 0.43 to 0.56), prior use of ICS (OR 2.28;
      95% CI 2.00 to 2.61), and filling a prescription for oral corticosteroids in the
      month following discharge (OR 2.29; 95% CI 2.03 to 2.58). However, patients who
      had an ED visit or a hospital admission for asthma during the 6 months before
      discharge were not more likely to use ICS after discharge. CONCLUSION: A large
      proportion of patients with clear markers of uncontrolled or severe asthma did
      not have a valid prescription for an ICS after discharge from the ED.

PMID- 15516469
TI  - Burkholderia cenocepacia and Burkholderia multivorans: influence on survival in
      cystic fibrosis.
AB  - INTRODUCTION: Burkholderia cepacia infection has been associated with a poor
      prognosis for patients with cystic fibrosis (CF). It is now recognised that
      organisms classified as B cepacia comprise a number of distinct genomic species
      each known as a genomovar of the B cepacia complex (BCC). The outcome of
      infection for CF patients with individual genomovars is unknown. The clinical
      outcome of infection with the two most commonly isolated genomovars (B
      cenocepacia and B multivorans) was studied at a specialist CF centre between 1982
      and 2003. METHODS: The numbers of patients who progressed from initial to chronic
      infection were assessed. Control groups were created by matching patients with
      chronic BCC infection by percentage forced expiratory volume in 1 second with
      patients with Pseudomonas aeruginosa infection. Outcome measures were survival
      time, deaths from "cepacia syndrome", rate of decline in spirometry and body mass
      index (BMI), and treatment requirements. RESULTS: Forty nine patients had an
      initial infection with either B multivorans (n = 16) or B cenocepacia (n = 33);
      8/16 and 31/33, respectively, developed chronic infection (p<0.001). Deaths from
      "cepacia syndrome" occurred in both BCC groups. Patients with B cenocepacia
      infection had a shorter survival than patients with P aeruginosa infection (p =
      0.01). There was no difference in survival between CF patients infected with B
      multivorans and P aeruginosa. There were no observed differences in changes in
      spirometry and BMI or treatment requirements between the BCC groups and
      respective controls. CONCLUSION: In CF, the genomovar status of BCC may influence
      both the likelihood of progression from initial to chronic infection and the
      overall survival of the patients.

PMID- 15516470
TI  - Recovery of Burkholderia cenocepacia strain PHDC from cystic fibrosis patients in
      Europe.
AB  - BACKGROUND: Burkholderia cenocepacia can cause life threatening respiratory tract
      infections in patients with cystic fibrosis (CF) and has a significant impact on
      survival. There is extensive evidence for patient to patient spread and
      nosocomial transmission of this organism, and several widespread B cenocepacia
      strains have been described including the transatlantic ET12 clone. A study was
      performed to compare B cenocepacia isolates recovered from CF patients receiving
      care in several European countries and strains isolated from other clinical
      samples and the environment, with reference isolates from the epidemic B
      cenocepacia strain PHDC which has so far only been recovered from CF patients and
      soil in the USA. METHODS: A large collection of B cenocepacia isolates, including
      a large number recovered from CF patients receiving care in several European
      countries, Canada and the USA, were genotyped by means of randomly amplified
      polymorphic DNA typing (RAPD) and rep-PCR using the BOX-A1R primer (BOX-PCR).
      RESULTS: Nineteen Burkholderia cenocepacia isolates cultured from clinical
      samples in Europe (18 recently recovered from CF patients in France and Italy and
      one recovered in 1964 from urine in the UK) showed RAPD fingerprinting patterns
      that were similar to patterns obtained from isolates of B cenocepacia strain
      PHDC. Subsequent analysis of these isolates using BOX-PCR confirmed that the
      European isolates and strain PHDC represent the same clone. CONCLUSION: Strain
      PHDC represents a second transatlantic B cenocepacia clone capable of colonising
      patients with CF.

PMID- 15516471
TI  - Association between Stenotrophomonas maltophilia and lung function in cystic
      fibrosis.
AB  - BACKGROUND: Stenotrophomonas maltophilia (SM) is a Gram-negative non-fermenting
      bacteria cultured from the sputum of patients with cystic fibrosis (CF). To date,
      no information is available regarding the effect of this organism on lung
      function in CF. METHODS: A cohort study was conducted to assess the effect of SM
      on lung function among CF patients aged > or =6 years in the CF Foundation
      National Patient Registry from 1994 to 1999. Repeated measures regression was
      used to assess the association between SM and lung function. RESULTS: The cohort
      consisted of 20 755 patients with median age at entry of 13.8 years and median
      follow up time of 3.8 years; 2739 patients (13%) were positive at least once for
      SM and 18 016 (87%) were never positive. After adjusting for sex, height and age,
      patients with SM had a mean forced expiratory volume in 1 second which was 0.09 l
      less (95% CI 0.05 to 0.14) than those without SM. The mean rate of decline
      associated with SM positivity was 0.025 l/year (95% CI 0.012 to 0.037) but, after
      adjusting for confounders (sex, height, weight, intravenous antibiotic courses,
      hospital admissions, pancreatic insufficiency, and Pseudomonas aeruginosa and
      Burkholderia cepacia status), the mean rate of decline decreased to 0.008 l/year
      (-0.008, 95% CI -0.019 to 0.003). CONCLUSIONS: Although CF patients with SM have
      worse lung function at the time of positivity, no association was found between
      SM and increased rate of decline after controlling for confounders.

PMID- 15516472
TI  - Risk factors of treatment failure in community acquired pneumonia: implications
      for disease outcome.
AB  - BACKGROUND: An inadequate response to initial empirical treatment of community
      acquired pneumonia (CAP) represents a challenge for clinicians and requires early
      identification and intervention. A study was undertaken to quantify the incidence
      of failure of empirical treatment in CAP, to identify risk factors for treatment
      failure, and to determine the implications of treatment failure on the outcome.
      METHODS: A prospective multicentre cohort study was performed in 1424
      hospitalised patients from 15 hospitals. Early treatment failure (<72 hours),
      late treatment failure, and in-hospital mortality were recorded. RESULTS:
      Treatment failure occurred in 215 patients (15.1%): 134 early failure (62.3%) and
      81 late failure (37.7%). The causes were infectious in 86 patients (40%), non
      infectious in 34 (15.8%), and undetermined in 95. The independent risk factors
      associated with treatment failure in a stepwise logistic regression analysis were
      liver disease, pneumonia risk class, leucopenia, multilobar CAP, pleural
      effusion, and radiological signs of cavitation. Independent factors associated
      with a lower risk of treatment failure were influenza vaccination, initial
      treatment with fluoroquinolones, and chronic obstructive pulmonary disease
      (COPD). Mortality was significantly higher in patients with treatment failure
      (25% v 2%). Failure of empirical treatment increased the mortality of CAP 11-fold
      after adjustment for risk class. CONCLUSIONS: Although these findings need to be
      confirmed by randomised studies, they suggest possible interventions to decrease
      mortality due to CAP.

PMID- 15516473
TI  - Effect of simulated commercial flight on oxygenation in patients with
      interstitial lung disease and chronic obstructive pulmonary disease.
AB  - BACKGROUND: Commercial aircraft cabins provide a hostile environment for patients
      with underlying respiratory disease. Although there are algorithms and guidelines
      for predicting in-flight hypoxaemia, these relate to chronic obstructive
      pulmonary disease (COPD) and data for interstitial lung disease (ILD) are
      lacking. The purpose of this study was to evaluate the effect of simulated cabin
      altitude on subjects with ILD at rest and during a limited walking task. METHODS:
      Fifteen subjects with ILD and 10 subjects with COPD were recruited. All subjects
      had resting arterial oxygen pressure (PaO2) of >9.3 kPa. Subjects breathed a
      hypoxic gas mixture containing 15% oxygen with balance nitrogen for 20 minutes at
      rest followed by a 50 metre walking task. Pulse oximetry (SpO2) was monitored
      continuously with testing terminated if levels fell below 80%. Arterial blood gas
      tensions were taken on room air at rest and after the resting and exercise phases
      of breathing the gas mixture. RESULTS: In both groups there was a statistically
      significant decrease in arterial oxygen saturation (SaO2) and PaO2 from room air
      to 15% oxygen at rest and from 15% oxygen at rest to the completion of the
      walking task. The ILD group differed significantly from the COPD group in resting
      15% oxygen SaO2, PaO2, and room air pH. Means for both groups fell below
      recommended levels at both resting and when walking on 15% oxygen. CONCLUSION:
      Even in the presence of acceptable arterial blood gas tensions at sea level,
      subjects with both ILD and COPD fall below recommended levels of oxygenation when
      cabin altitude is simulated. This is exacerbated by minimal exercise. Resting sea
      level arterial blood gas tensions are similarly poor in both COPD and ILD for
      predicting the response to simulated cabin altitude.

PMID- 15516474
TI  - Nasal airway ion transport is linked to the cystic fibrosis phenotype in adult
      patients.
AB  - BACKGROUND: This study was conducted to determine whether the major nasal airway
      ion transport abnormalities in cystic fibrosis (that is, defective cAMP regulated
      chloride secretion and basal sodium hyperabsorption) are related to the clinical
      expression of cystic fibrosis and/or to the genotype. METHODS: Nasal potential
      difference was measured in 79 adult patients with cystic fibrosis for whom
      clinical status, respiratory function, and CFTR genotype were determined.
      RESULTS: In univariate and multivariate analysis, patients with pancreatic
      insufficiency were more likely to have low responses to low chloride (odds ratio
      (OR) 8.6 (95% CI 1.3 to 58.5), p = 0.03) and isoproterenol (OR 11.2 (95% CI 1.3
      to 93.9), p = 0.03) solutions. Similarly, in univariate and multivariate
      analysis, patients with poor respiratory function (forced expiratory volume in 1
      second <50% of predicted value) were more likely to have an enhanced response to
      amiloride solution (OR 3.7 (95% CI 1.3 to 11.0), p = 0.02). However, there was no
      significant relationship between nasal potential difference and the severity of
      the genotype. CONCLUSIONS: Nasal epithelial ion transport in cystic fibrosis is
      linked to the clinical expression of the disease. The pancreatic status appears
      to be mostly related to the defect in epithelial chloride secretion whereas the
      respiratory status is mostly related to abnormal sodium transport and the
      regulatory function of the CFTR protein.

PMID- 15516475
TI  - Genetic mutations in surfactant protein C are a rare cause of sporadic cases of
      IPF.
AB  - BACKGROUND: While idiopathic pulmonary fibrosis (IPF) is one of the most common
      forms of interstitial lung disease, the aetiology of IPF is poorly understood.
      Familial cases of pulmonary fibrosis suggest a genetic basis for some forms of
      the disease. Recent reports have linked genetic mutations in surfactant protein C
      (SFTPC) with familial forms of pulmonary fibrosis, including one large family in
      which a number of family members were diagnosed with usual interstitial
      pneumonitis (UIP), the pathological correlate to IPF. Because of this finding in
      familial cases of pulmonary fibrosis, we searched for SFTPC mutations in a cohort
      of sporadic cases of UIP and non-specific interstitial pneumonitis (NSIP).
      METHODS: The gene for SFTPC was sequenced in 89 patients diagnosed with UIP, 46
      patients with NSIP, and 104 normal controls. RESULTS: Ten single nucleotide
      polymorphisms in the SFTPC sequence were found in IPF patients and not in
      controls. Only one of these created an exonic change resulting in a change in
      amino acid sequence. In this case, a T to C substitution resulted in a change in
      amino acid 73 of the precursor protein from isoleucine to threonine. Of the
      remaining polymorphisms, one was in the 5' UTR, two were exonic without predicted
      amino acid sequence changes, and six were intronic. One intronic mutation
      suggested a potential enhancement of a splicing site. CONCLUSIONS: Mutations in
      SFTPC are identified infrequently in this patient population. These findings
      indicate that SFTPC mutations do not contribute to the pathogenesis of IPF in the
      majority of sporadic cases.

PMID- 15516476
TI  - Type of wine and risk of lung cancer: a case-control study in Spain.
AB  - BACKGROUND: Few epidemiological studies have examined the effect of wine on the
      risk of lung cancer. A study was therefore undertaken to estimate the effect of
      wine consumption, both overall and by type of wine, on the risk of developing
      lung cancer. METHODS: A hospital based case-control study was conducted on 319
      subjects (132 cases, 187 controls) in 1999-2000. All subjects were interviewed
      about their lifestyles with particular reference to alcohol consumption and
      tobacco use. The results were analysed using non-parametric logistic regression.
      The main outcome measure was the risk of lung cancer associated with consumption
      of wine and its individual types. RESULTS: A very slight but significant
      association was observed between the risk of lung cancer and white wine
      consumption (odds ratio (OR) 1.20 for each daily glass). Red wine consumption, on
      the other hand, had an OR of 0.43 (95% CI 0.19 to 0.96), with each daily glass of
      red wine having an inverse association with the development of lung cancer (OR
      0.87 (95% CI 0.77 to 0.99)). There was no apparent association between lung
      cancer and consumption of beer or spirits. CONCLUSIONS: These results suggest
      that the consumption of red wine is negatively associated with the development of
      lung cancer. Further studies are needed to test this finding in cancer induced
      laboratory animals.

PMID- 15516477
TI  - Alpha1-antitrypsin deficiency. 7: Computed tomographic imaging in alpha1
      antitrypsin deficiency.
AB  - Computed tomographic scanning may replace lung function tests as the golden
      standard for assessing the response to known and novel treatments for alpha1
      antitrypsin deficiency.

PMID- 15516478
TI  - Roles of epidermal growth factor receptor activation in epithelial cell repair
      and mucin production in airway epithelium.
AB  - The epithelial cells lining the airways serve protective functions. The "barrier
      function" of the epithelium protects the individual from damage by inhaled
      irritants. The epithelium produces mucins which become hydrated and form a
      viscoelastic gel which spreads over the epithelial surface. In healthy
      individuals inhaled foreign materials become entrapped in the mucus and are
      cleared by mucociliary transport and by coughing. In many chronic inflammatory
      airway diseases, however, excessive mucus is produced and is inadequately
      cleared, leading to mucous obstruction and infection. At present there is no
      specific treatment for hypersecretion. However, the discovery that an epidermal
      growth factor receptor (EGFR) cascade is involved in mucin production by a wide
      variety of stimuli suggests that blockade may provide specific treatment for
      hypersecretory diseases. EGFR pathways have also been implicated in the repair of
      damaged airway epithelium. The roles of EGFR in airway epithelial cell
      hypersecretion and epithelial damage and repair are reviewed and future potential
      treatments are suggested.

PMID- 15516479
TI  - Concurrent granulomatous Pneumocystis carinii and Mycobacterium xenopi pneumonia:
      an unusual manifestation of HIV immune reconstitution disease.
AB  - This report of concurrent granulomatous Pneumocystis carinii pneumonia (GPCP) and
      Mycobacterium xenopi pneumonia (MXIP) in a patient with advanced HIV disease 3-5
      weeks after commencing antiretroviral therapy (ART) fits the syndrome of HIV
      immune reconstitution/restoration disease (IRD). It may also be a unique window
      into the immunology of granulomatous inflammation.

PMID- 15516480
TI  - eNOS allelic variants at the same locus associate with HAPE and adaptation.

PMID- 15516481
TI  - Pre-flight hypoxic challenge in infants and young children with respiratory
      disease.

PMID- 15516482
TI  - Prevalence of TB in healthcare workers in south west London.

PMID- 15516484
TI  - Idiopathic diffuse pulmonary ossification.

PMID- 15516485
TI  - Pseudomonas aeruginosa protease IV degrades surfactant proteins and inhibits
      surfactant host defense and biophysical functions.
AB  - Pulmonary surfactant has two distinct functions within the lung: reduction of
      surface tension at the air-liquid interface and participation in innate host
      defense. Both functions are dependent on surfactant-associated proteins.
      Pseudomonas aeruginosa is primarily responsible for respiratory dysfunction and
      death in cystic fibrosis patients and is also a leading pathogen in nosocomial
      pneumonia. P. aeruginosa secretes a number of proteases that contribute to its
      virulence. We hypothesized that P. aeruginosa protease IV degrades surfactant
      proteins and results in a reduction in pulmonary surfactant host defense and
      biophysical functions. Protease IV was isolated from cultured supernatant of P.
      aeruginosa by gel chromatography. Incubation of cell-free bronchoalveolar lavage
      fluid with protease IV resulted in degradation of surfactant proteins (SP)-A, -D,
      and -B. SPs were degraded in a time- and dose-dependent fashion by protease IV,
      and degradation was inhibited by the trypsin-like serine protease inhibitor
      Nalpha-p-tosyl-L-lysine-chloromethyl ketone (TLCK). Degradation by protease IV
      inhibited SP-A- and SP-D-mediated bacterial aggregation and uptake by
      macrophages. Surfactant treated with protease IV was unable to reduce surface
      tension as effectively as untreated surfactant, and this effect was inhibited by
      TLCK. We speculate that protease IV may be an important contributing factor to
      the development and propagation of acute lung injury associated with P.
      aeruginosa via loss of surfactant function within the lung.

PMID- 15516486
TI  - Characterization of cigarette smoke-induced inflammatory and mucus hypersecretory
      changes in rat lung and the role of CXCR2 ligands in mediating this effect.
AB  - Repetitive, acute inflammatory insults elicited by cigarette smoke (CS)
      contribute to the development of chronic obstructive pulmonary disease (COPD), a
      disorder associated with lung inflammation and mucus hypersecretion. Presently,
      there is a poor understanding of the acute inflammatory mechanisms involved in
      this process. The aims of this study were to develop an acute model to
      investigate temporal inflammatory changes occurring after CS exposure. Rats were
      exposed to whole body CS (once daily) generated from filtered research
      cigarettes. Initial studies indicated the generation of a neutrophilic/mucus
      hypersecreting lung phenotype in <4 days. Subsequent studies demonstrated that
      just two exposures to CS (15 h apart) elicited a robust inflammatory/mucus
      hypersecretory phenotype that was used to investigate mechanisms driving this
      response. Cytokine-induced neutrophil chemoattractants (CINCs) 1-3, the rat
      growth-related oncogene-alpha family homologs, and IL-1beta demonstrated time
      dependent increases in lung tissue or lavage fluid over the 24-h period following
      CS exposure. The temporal changes in the neutrophil chemokines, CINCs 1-3,
      mirrored increases in neutrophil infiltration, indicative of a role in neutrophil
      migration. In addition, a specific CXCR2 antagonist, SB-332235, effectively
      inhibited CS-induced neutrophilia in a dose-dependent manner, supporting this
      conclusion. This modeling of the response of the rat airways to acute CS exposure
      indicates 1) as few as two exposures to CS will induce a phenotype with
      similarities to COPD and 2) a novel role for CINCs in the generation of this
      response. These observations represent a paradigm for the study of acute,
      repetitive lung insults that contribute to the development of chronic disease.

PMID- 15516487
TI  - Bronchial epithelium-associated pulmonary arterial muscle relaxation in the rat
      is absent in the fetus and suppressed by postnatal hypoxia.
AB  - We recently reported the existence of a bronchial epithelium-derived relaxing
      factor (BrEpRF) capable of reducing pulmonary arterial smooth muscle force
      generation in the newborn rat. We reasoned in this study that BrEpRF has
      physiological significance in the control of pulmonary vascular tone. We
      hypothesized that the release and/or activity of this factor can be stimulated
      and is suppressed prenatally or under hypoxic conditions postnatally. Therefore,
      we evaluated the pathways stimulated by the BrEpRF in fetal and newborn rat
      intrapulmonary arteries mounted with their adjacent bronchi in a wire myograph
      under both normoxic and hypoxic conditions. Under normoxic conditions, BrEpRF
      release/activation was observed in newborn vessels following methacholine
      stimulation of M(2) muscarinic receptors, which was mediated via a nitric oxide
      (NO)-dependent mechanism involving the phosphatidylinositol 3-kinase pathway.
      Hypoxia suppressed the BrEpRF-dependent modulation of basal and methacholine
      induced pulmonary arterial muscle tone in newborn vessels without altering
      endothelium-dependent or -independent NO-mediated relaxation. In fetal pulmonary
      arteries studied under normoxic conditions, BrEpRF neither was active under basal
      conditions nor could it be stimulated with methacholine. We conclude that
      release/activation of the BrEpRF occurs by an oxygen-dependent mechanism in the
      newborn and is suppressed during late fetal life. These results suggest that the
      BrEpRF may be involved in postnatal adaptation of the pulmonary circulation and
      that its suppression may contribute to hypoxic pulmonary vasoconstriction.

PMID- 15516488
TI  - Elevated plasma levels of soluble TNF receptors are associated with morbidity and
      mortality in patients with acute lung injury.
AB  - Ventilator-induced lung injury (VILI) is an inflammatory process that can be
      attenuated by lung protective ventilation strategies. Our objectives to further
      investigate the pathogenesis of ALI and VILI and the mechanism of lung protection
      in these syndromes were: 1) to determine if plasma measurements of soluble TNF
      receptor I (sTNFRI) and II (sTNFRII) would predict the development of ALI and
      mortality in a small single center trial; 2) to test the predictive value of
      these markers and of TNF-alpha in a larger, broader group of patients with ALI;
      3) to test the hypothesis that low tidal volume ventilation (LTVV) would be
      associated with a decrease in plasma levels of TNF-alpha, sTNFRI, and sTNFRII. In
      the single center study, sTNFRI and II levels were higher in patients at risk for
      and with ALI, but they did not predict the development of the syndrome. In the
      multicenter trial sTNFRI and II were strongly associated with mortality (OR
      5.76/1 log10 increment in receptor level; 95% CI 2.63-12.6 and OR 2.58; 95% CI
      1.05-6.31, respectively) and morbidity measured as fewer nonpulmonary organ
      failure-free and ventilator-free days. The LTVV strategy was associated with an
      attenuation of plasma sTNFRI levels. In vitro, stimulated A549 cells release
      sTNFRI but not sTNRFII. In conclusion, plasma levels of sTNFRI and II can serve
      as biomarkers for morbidity and mortality in patients with ALI. Furthermore, LTVV
      is associated with a specific decrease in sTNFRI levels. This suggests that one
      beneficial effect of LTVV may be to attenuate alveolar epithelial injury.

PMID- 15516489
TI  - Voltage-gated proton channels help regulate pHi in rat alveolar epithelium.
AB  - Voltage-gated proton channels are expressed highly in rat alveolar epithelial
      cells. Here we investigated whether these channels contribute to pH regulation.
      The intracellular pH (pH(i)) was monitored using BCECF in cultured alveolar
      epithelial cell monolayers and found to be 7.13 in nominally HCO(3)(-)-free
      solutions [at external pH (pH(o)) 7.4]. Cells were acid-loaded by the NH(4)(+)
      prepulse technique, and the recovery was observed. Under conditions designed to
      eliminate the contribution of other transporters that alter pH, addition of 10
      microM ZnCl(2), a proton channel inhibitor, slowed recovery about twofold. In
      addition, the pH(i) minimum was lower, and the time to nadir was increased.
      Slowing of recovery by ZnCl(2) was observed at pH(o) 7.4 and pH(o) 8.0 and in
      normal and high-K(+) Ringer solutions. The observed rate of Zn(2+)-sensitive
      pH(i) recovery required activation of a small fraction of the available proton
      conductance. We conclude that proton channels contribute to pH(i) recovery after
      an acid load in rat alveolar epithelial cells. Addition of ZnCl(2) had no effect
      on pH(i) in unchallenged cells, consistent with the expectation that proton
      channels are not open in resting cells. After inhibition of all known pH
      regulators, slow pH(i) recovery persisted, suggesting the existence of a yet
      undefined acid extrusion mechanism in these cells.

PMID- 15516490
TI  - MKK3 and -6-dependent activation of p38alpha MAP kinase is required for
      cytoskeletal changes in pulmonary microvascular endothelial cells induced by ICAM
      1 ligation.
AB  - Previous studies demonstrated that neutrophil adherence induces ICAM-1-dependent
      cytoskeletal changes in TNF-alpha-treated pulmonary microvascular endothelial
      cells that are prevented by a pharmacological inhibitor of p38 MAP kinase. This
      study determined whether neutrophil adherence induces activation of p38 MAP
      kinase in endothelial cells, the subcellular localization of phosphorylated p38,
      which MAP kinase kinases lead to p38 activation, which p38 isoform is activated,
      and what the downstream targets may be. Confocal microscopy showed that
      neutrophil adhesion for 2 or 6 min induced an increase in phosphorylated p38 in
      endothelial cells that was punctate and concentrated in the central region of the
      endothelial cells. Studies using small interfering RNA (siRNA) to inhibit the
      protein expression of MAP kinase kinase 3 and 6, either singly or in combination,
      showed that both MAP kinase kinases were required for p38 phosphorylation.
      Studies using an antisense oligonucleotide to p38alpha demonstrated that
      inhibition of the protein expression of p38alpha 1) inhibited activation of p38
      MAP kinase without affecting the protein expression of p38beta; 2) prevented
      phosphorylation of heat shock protein 27, an actin binding protein that may
      induce actin polymerization upon phosphorylation; 3) attenuated cytoskeletal
      changes; and 4) attenuated neutrophil migration to the EC borders. Thus MAP
      kinase kinase3- and 6-dependent activation of the alpha-isoform of p38 MAP kinase
      is required for the cytoskeletal changes induced by neutrophil adherence and
      influences subsequent neutrophil migration toward endothelial cell junctions.

PMID- 15516491
TI  - Lysophospholipid generation and phosphatidylglycerol depletion in phospholipase
      A(2)-mediated surfactant dysfunction.
AB  - Pulmonary surfactant's complex mixture of phospholipids and proteins reduces the
      work of breathing by lowering alveolar surface tension during respiration. One
      mechanism of surfactant damage appears to be the hydrolysis of phospholipid by
      phospholipases activated in the inflamed lung. Humans have several candidate
      secretory phospholipase A(2) (sPLA(2)) enzymes in lung cells and infiltrating
      leukocytes that could damage extracellular surfactant. We considered two
      mechanisms of surfactant disruption by five human sPLA(2)s, including generation
      of lysophospholipids and the depletion of specific phospholipids. All five
      sPLA(2)s studied ultimately caused surfactant dysfunction. Each enzyme exhibited
      a different pattern of hydrolysis of surfactant phospholipids.
      Phosphatidylcholine, the major phospholipid in surfactant and the greatest
      potential source for generation of lysophospholipids, was susceptible to
      hydrolysis by group IB, group V, and group X sPLA(2)s, but not group IIA or IID.
      Group IIA hydrolyzed both phosphatidylethanolamine and phosphatidylglycerol,
      whereas group IID was active against only phosphatidylglycerol. Thus, with groups
      IB and X, the generation of lysophospholipids corresponded with surfactant
      dysfunction. However, hydrolysis of and depletion of phosphatidylglycerol had a
      greater correlation with surfactant dysfunction for groups IIA and IID.
      Surfactant dysfunction caused by group V sPLA(2) is less clear and may be the
      combined result of both mechanisms.

PMID- 15516492
TI  - BMP4 inhibits proliferation and promotes myocyte differentiation of lung
      fibroblasts via Smad1 and JNK pathways.
AB  - Fibroblast proliferation, differentiation, and migration contribute to the
      characteristic pulmonary vascular remodeling seen in primary pulmonary
      hypertension (PPH). The identification of mutations in the bone morphogenetic
      protein type II receptor (BMPRII) in PPH have led us to question what role BMPRII
      and its ligands play in pulmonary vascular remodeling. Thus, to further
      understand the functional significance of BMPRII in the pulmonary vasculature, we
      examined the expression of TGF-beta superfamily receptors in human fetal lung
      fibroblasts (HFL) and investigated the role of BMP4 on cell cycle regulation,
      fibroblast proliferation, and differentiation. Furthermore, signaling pathways
      involved in these processes were examined. HFL expressed BMPRI and BMPRII mRNA
      and demonstrated specific I(125)-BMP4 binding sites. BMP4 inhibited
      [(3)H]thymidine incorporation and proliferation of HFL; protein expression was
      increased for the cell cycle inhibitor p21 and reduced for the positive
      regulators cyclin D and cdk2 by BMP4. BMP4 induced differentiation of HFL into a
      smooth muscle cell phenotype since protein expression of alpha-smooth muscle
      actin and smooth muscle myosin was increased. Furthermore, p38(MAPK), ERK1/2,
      JNK, and Smad1 were phosphorylated by BMP4. Using specific MAPK inhibitors, a
      dominant negative Smad1 construct, and Smad1 siRNA, we found that the
      antiproliferative and prodifferentiation effects of BMP4 were Smad1 dependent
      with JNK also contributing to differentiation. Because failure of Smad
      phosphorylation is a major feature of BMPRII mutations, these results imply that
      BMPRII mutations may promote the expansion of fibroblasts resistant to the
      antiproliferative, prodifferentiation effects of BMPs and suggest a mechanism for
      the vascular obliteration seen in familial PPH.

PMID- 15516493
TI  - NF-kappaB activation and sustained IL-8 gene expression in primary cultures of
      cystic fibrosis airway epithelial cells stimulated with Pseudomonas aeruginosa.
AB  - The progression of lung disease in cystic fibrosis (CF) is characterized by an
      exuberant inflammatory response mounted by the respiratory epithelium that is
      further exacerbated by bacterial infection. Recent studies have demonstrated
      upregulation of nuclear factor-kappaB (NF-kappaB) in response to infection in
      genetically modified cell culture models, which is associated with expression of
      interleukin (IL)-8. Using human airway epithelial cells grown in primary culture,
      we examined in vitro activation of NF-kappaB in cells isolated from five CF
      (DeltaF508/DeltaF508) and three non-CF (NCF) patients in response to Pseudomonas
      aeruginosa. Immunofluorescence, gel-shift, and immunoblot assays demonstrated a
      rapid translocation of NF-kappaB subunits (p50 and p65) to the nucleus in both CF
      and NCF cell cultures. However, nuclear extracts from CF cells both before and
      following P. aeruginosa stimulation revealed elevated NF-kappaB activation
      compared with NCF cells. Additionally, elevated nuclear levels of the NF-kappaB
      inhibitor IkappaBalpha were detected in nuclei of CF cells after P. aeruginosa
      stimulation, but this increase was transient. There was no difference in IL-8
      mRNA levels between CF and NCF cells early after stimulation, whereas expression
      was higher and sustained in CF cells at later times. Our results also
      demonstrated increased baseline translocation of NF-kappaB to nuclei of primary
      CF epithelial cell cultures, but intranuclear IkappaBalpha may initially block
      its effects following P. aeruginosa stimulation. Thus, IL-8 mRNA expression was
      prolonged after P. aeruginosa stimulation in CF epithelial cells, and this
      sustained IL-8 expression may contribute to the excessive inflammatory response
      in CF.

PMID- 15516494
TI  - CCR2-positive monocytes recruited to inflamed lungs downregulate local CCL2
      chemokine levels.
AB  - The CC chemokine ligand-2 (CCL2) and its receptor CCR2 are essential for monocyte
      trafficking under inflammatory conditions. However, the mechanisms that determine
      the intensity and duration of alveolar monocyte accumulation in response to CCL2
      gradients in inflamed lungs have not been resolved. To determine the potential
      role of CCR2-expressing monocytes in regulating alveolar CCL2 levels, we compared
      leukocyte recruitment kinetics and alveolar CCL2 levels in wild-type and CCR2
      deficient mice in response to intratracheal LPS challenge. In wild-type mice, LPS
      elicited a dose- and time-dependent alveolar monocyte accumulation accompanied by
      low CCL2 levels in bronchoalveolar lavage fluid (BALF). In contrast, LPS-treated
      CCR2-deficient mice lacked alveolar monocyte accumulation, which was accompanied
      by relatively high CCL2 levels in BALF. Similarly, wild-type mice that were
      treated systemically with the blocking anti-CCR2 antibody MC21 completely lacked
      LPS-induced alveolar monocyte trafficking that was associated with high CCL2
      levels in BALF. Intratracheal application of anti-CCR2 antibody MC21 to locally
      block CCR2 on both resident and recruited cells did not affect LPS-induced
      alveolar monocyte trafficking but led to significantly increased BALF CCL2
      levels. Reciprocally bone marrow-transplanted, LPS-treated wild-type and CCR2
      deficient mice showed a strict inverse relationship between alveolar monocyte
      recruitment and BALF CCL2 levels. In addition, freshly isolated human and mouse
      monocytes were capable of integrating CCL2 in vitro. LPS-induced alveolar
      monocyte accumulation is accompanied by monocytic CCR2-dependent consumption of
      CCL2 levels in the lung. This feedback loop may limit the intensity of monocyte
      recruitment to inflamed lungs and play a role in the maintenance of homeostasis.

PMID- 15516495
TI  - Role of interleukin-6 in murine airway responses to ozone.
AB  - This study sought to examine the role of interleukin-6 (IL-6) in ozone (O(3))
      induced airway injury, inflammation, and hyperresponsiveness (AHR). Subacute (72
      h) exposure to 0.3 ppm O(3) significantly elevated bronchoalveolar lavage fluid
      (BALF) protein, neutrophils, and soluble TNF receptors (sTNFR1 and sTNFR2) in
      wild-type C57BL/6 (IL-6(+/+)) mice; however, all four outcome indicators were
      significantly reduced in IL-6-deficient (IL-6(-/-)) compared with IL-6(+/+) mice.
      Acute O(3) exposure (2 ppm for 3 h) increased BALF protein, KC, macrophage
      inflammatory protein(MIP)-2, eotaxin, sTNFR1, and sTNFR2 in IL-6(+/+) mice.
      However, MIP-2 and sTNFR2 were not significantly increased following O(3)
      exposure in IL-6(-/-) mice. Increases in BALF neutrophils induced by O(3) (2 ppm
      for 3 h) were also significantly reduced in IL-6(-/-) vs. IL-6(+/+) mice. Airway
      responsiveness to methacholine was measured by whole body plethysmography before
      and following acute (3 h) or subacute (72 h) exposure to 0.3 ppm O(3). Acute O(3)
      exposure caused AHR in both groups of mice, but there was no genotype-related
      difference in the magnitude of O(3)-induced AHR. AHR was absent in mice of either
      genotype exposed for 72 h. Our results indicate that IL-6 deficiency reduces
      airway neutrophilia, as well as the levels of BALF sTNFR1 and sTNFR2 following
      acute high dose and/or subacute low-dose O(3) exposure, but has no effect on O(3)
      induced AHR.

PMID- 15516496
TI  - Arabidopsis NAP and PIR regulate actin-based cell morphogenesis and multiple
      developmental processes.
AB  - The actin cytoskeleton mediates cellular processes through the dynamic regulation
      of the time, location, and extent of actin polymerization. Actin polymerization
      is controlled by several types of evolutionarily conserved proteins, including
      those comprising the ARP2/3 complex. In animal cells ARP2/3 activity is regulated
      by WAVE complexes that contain WAVE/SCAR proteins, PIR121, Nap125, and other
      proteins. The activity of the WAVE complex is regulated by Rho-GTPase-mediated
      signaling that leads to ARP2/3 activation by WAVE/SCAR proteins. We describe in
      this report Arabidopsis (Arabidopsis thaliana) genes encoding Nap and PIR
      proteins. Light-grown Atnap-1 and Atpir-1 mutant plants displayed altered leaf,
      inflorescence, silique, and seed set phenotypes. Dark-grown Atnap-1 and Atpir-1
      seedlings also exhibited longer roots, enhanced skotomorphogenesis and Glc
      responses, and shorter thicker hypocotyls than those of wild type, showing that
      AtNAP and AtPIR participate in a variety of growth and developmental processes.
      Mutations in AtNAP and AtPIR caused cell morphology defects in cotyledon pavement
      cells and trichomes seen in mutants in ARP2/3 subunits and in plants expressing
      constitutively active Rop2 GTPase. The patterns and levels of actin
      polymerization observed in Atnap-1 and Atpir-1 mutant trichome cells and
      epidermal pavement cell morphology is consistent with Arabidopsis NAP and PIR
      proteins forming a WAVE complex that activates ARP2/3 activity. The multiple
      growth and developmental phenotypes of Atnap and Atpir mutants reveals these
      proteins are also required for a wider variety of cellular functions in addition
      to regulating trichome cell growth.

PMID- 15516497
TI  - A stromal Hsp100 protein is required for normal chloroplast development and
      function in Arabidopsis.
AB  - Molecular chaperones are required for the translocation of many proteins across
      organellar membranes, presumably by providing energy in the form of ATP
      hydrolysis for protein movement. In the chloroplast protein import system, a heat
      shock protein 100 (Hsp100), known as Hsp93, is hypothesized to be the chaperone
      providing energy for precursor translocation, although there is little direct
      evidence for this hypothesis. To learn more about the possible function of Hsp93
      during protein import into chloroplasts, we isolated knockout mutant lines that
      contain T-DNA disruptions in either atHSP93-V or atHSP93-III, which encode the
      two Arabidopsis (Arabidopsis thaliana) homologs of Hsp93. atHsp93-V mutant plants
      are much smaller and paler than wild-type plants. In addition, mutant
      chloroplasts contain less thylakoid membrane when compared to the wild type.
      Plastid protein composition, however, seems to be largely unaffected in atHsp93-V
      knockout plants. Chloroplasts isolated from the atHsp93-V knockout mutant line
      are still able to import a variety of precursor proteins, but the rate of import
      of some of these precursors is significantly reduced. These results indicate that
      atHsp93-V has an important, but not essential, role in the biogenesis of
      Arabidopsis chloroplasts. In contrast, knockout mutant plants for atHsp93-III,
      the second Arabidopsis Hsp93 homolog, had a visible phenotype identical to the
      wild type, suggesting that atHsp93-III may not play as important a role as
      atHsp93-V in chloroplast development and/or function.

PMID- 15516498
TI  - Characterization of a xyloglucan endotransglucosylase gene that is up-regulated
      by gibberellin in rice.
AB  - Xyloglucan endotransglucosylases/hydrolases (XTHs) that mediate cleavage and
      rejoining of the beta (1-4)-xyloglucans of the primary cell wall are considered
      to play an important role in the construction and restructuring of xyloglucan
      cross-links. A novel rice (Oryza sativa) XTH-related gene, OsXTH8, was cloned and
      characterized after being identified by cDNA microarray analysis of gibberellin
      induced changes in gene expression in rice seedlings. OsXTH8 was a single copy
      gene; its full-length cDNA was 1,298 bp encoding a predicted protein of 290 amino
      acids. Phylogenetic analysis revealed that OsXTH8 falls outside of the three
      established subfamilies of XTH-related genes. OsXTH8 was preferentially expressed
      in rice leaf sheath in response to gibberellic acid. In situ hybridization and
      OsXTH8 promoter GUS fusion analysis revealed that OsXTH8 was highly expressed in
      vascular bundles of leaf sheath and young nodal roots where the cells are
      actively undergoing elongation and differentiation. OsXTH8 gene expression was up
      regulated by gibberellic acid and there was very little effect of other hormones.
      In two genetic mutants of rice with abnormal height, the expression of OsXTH8
      positively correlated with the height of the mutants. Transgenic rice expressing
      an RNAi construct of OsXTH8 exhibited repressed growth. These results indicate
      that OsXTH8 is differentially expressed in rice leaf sheath in relation to
      gibberellin and potentially involved in cell elongation processes.

PMID- 15516499
TI  - The Arabidopsis trehalose-6-P synthase AtTPS1 gene is a regulator of glucose,
      abscisic acid, and stress signaling.
AB  - In Arabidopsis (Arabidopsis thaliana), trehalose is present at almost
      undetectable levels, excluding its role as an osmoprotectant. Here, we report
      that overexpression of AtTPS1 in Arabidopsis using the 35S promoter led to a
      small increase in trehalose and trehalose-6-P levels. In spite of this,
      transgenic plants displayed a dehydration tolerance phenotype without any visible
      morphological alterations, except for delayed flowering. Moreover, seedlings
      overexpressing AtTPS1 exhibited glucose (Glc)- and abscisic acid (ABA)
      insensitive phenotypes. Transgenic seedlings germinated on Glc were visibly
      larger with green well-expanded cotyledonary leaves and fully developed roots, in
      contrast with wild-type seedlings showing growth retardation and absence of
      photosynthetic tissue. An ABA dose-response experiment revealed a higher
      germination rate for transgenic plants overexpressing AtTPS1 showing insensitive
      germination kinetics at 2.5 mum ABA. Interestingly, germination in the presence
      of Glc did not trigger an increase in ABA content in plants overexpressing
      AtTPS1. Expression analysis by quantitative reverse transcription-PCR in
      transgenic plants showed up-regulation of the ABI4 and CAB1 genes. In the
      presence of Glc, CAB1 expression remained high, whereas ABI4, HXK1, and ApL3
      levels were down-regulated in the AtTPS1-overexpressing lines. Analysis of AtTPS1
      expression in HXK1-antisense or HXK1-sense transgenic lines suggests the possible
      involvement of AtTPS1 in the hexokinase-dependent Glc-signaling pathway. These
      data strongly suggest that AtTPS1 has a pivotal role in the regulation of Glc and
      ABA signaling during vegetative development.

PMID- 15516500
TI  - The biochemical and molecular basis for the divergent patterns in the
      biosynthesis of terpenes and phenylpropenes in the peltate glands of three
      cultivars of basil.
AB  - Surface glandular trichomes distributed throughout the aerial parts of sweet
      basil (Ocimum basilicum) produce and store monoterpene, sesquiterpene, and
      phenylpropene volatiles. Three distinct basil chemotypes were used to examine the
      molecular mechanisms underlying the divergence in their monoterpene and
      sesquiterpene content. The relative levels of specific terpenes in the glandular
      trichomes of each cultivar were correlated with the levels of transcripts for
      eight genes encoding distinct terpene synthases. In a cultivar that produces
      mostly (R)-linalool, transcripts of (R)-linalool synthase (LIS) were the most
      abundant of these eight. In a cultivar that synthesizes mostly geraniol,
      transcripts of geraniol synthase were the most abundant, but the glands of this
      cultivar also contained a transcript of an (R)-LIS gene with a 1-base insertion
      that caused a frameshift mutation. A geraniol synthase-LIS hybrid gene was
      constructed and expressed in Escherichia coli, and the protein catalyzed the
      formation of both geraniol and (R)-linalool from geranyl diphosphate. The total
      amounts of terpenes were correlated with total levels of terpene synthase
      activities, and negatively correlated with levels of phenylpropanoids and
      phenylalanine ammonia lyase activity. The relative levels of geranyl diphosphate
      synthase and farnesyl diphosphate synthase activities did not correlate with the
      total amount of terpenes produced, but showed some correlation with the ratio of
      monoterpenes to sesquiterpenes.

PMID- 15516501
TI  - Deletion of the chloroplast-localized Thylakoid formation1 gene product in
      Arabidopsis leads to deficient thylakoid formation and variegated leaves.
AB  - Development of thylakoid membranes depends upon the transport of membrane
      vesicles from the chloroplast inner envelope and subsequent fusion of vesicles
      within the interior of the plastid. The Arabidopsis (Arabidopsis thaliana)
      Thylakoid formation1 (Thf1) gene product is shown here to control an important
      step required for the normal organization of these vesicles into mature thylakoid
      stacks and ultimately for leaf development. The Arabidopsis Thf1 gene encodes an
      imported chloroplast protein, as shown by in vitro import and localization of a
      Thf1-green fluorescent protein fusion product in transgenic plants. This gene is
      conserved in oxygenic photoautotrophs ranging from cyanobacteria to flowering
      land plants. Transcript levels for Thf1 are induced in the light and decrease
      under dark conditions, paralleling profiles of light-regulated nuclear genes
      involved in chloroplast function. Disruption of the Thf1 gene via T-DNA insertion
      results in plants that are severely stunted with variegated leaf patterns.
      Nongreen sectors of variegated leaves lacking Thf1 expression contain plastids
      that accumulate membrane vesicles on the interior and lack organized thylakoid
      structures. Green sectors of Thf1-disrupted leaves contain some chloroplasts that
      form organized thylakoid membranes, indicating that an inefficient compensatory
      mechanism supports thylakoid formation in the absence of Thf1. Genetic
      complementation of a Thf1 knockout line confirms the role of this gene in
      chloroplast and leaf development. Transgenic plants expressing the Thf1 gene in
      antisense orientation are stunted with altered thylakoid organization, especially
      in young seedlings. The data indicate that the Thf1 gene product plays a crucial
      role in a dynamic process of vesicle-mediated thylakoid membrane biogenesis.

PMID- 15516502
TI  - Circadian regulation of the PhCCD1 carotenoid cleavage dioxygenase controls
      emission of beta-ionone, a fragrance volatile of petunia flowers.
AB  - Carotenoids are thought to be the precursors of terpenoid volatile compounds that
      contribute to flavor and aroma. One such volatile, beta-ionone, is important to
      fragrance in many flowers, including petunia (Petunia hybrida). However, little
      is known about the factors regulating its synthesis in vivo. The petunia genome
      contains a gene encoding a 9,10(9',10') carotenoid cleavage dioxygenase, PhCCD1.
      The PhCCD1 is 94% identical to LeCCD1A, an enzyme responsible for formation of
      beta-ionone in tomato (Lycopersicon esculentum; Simkin AJ, Schwartz SH, Auldridge
      M, Taylor MG, Klee HJ [2004] Plant J [in press]). Reduction of PhCCD1 transcript
      levels in transgenic plants led to a 58% to 76% decrease in beta-ionone synthesis
      in the corollas of selected petunia lines, indicating a significant role for this
      enzyme in volatile synthesis. Quantitative reverse transcription-PCR analysis
      revealed that PhCCD1 is highly expressed in corollas and leaves, where it
      constitutes approximately 0.04% and 0.02% of total RNA, respectively. PhCCD1 is
      light-inducible and exhibits a circadian rhythm in both leaves and flowers. beta
      Ionone emission by flowers occurred principally during daylight hours,
      paralleling PhCCD1 expression in corollas. The results indicate that PhCCD1
      activity and beta-ionone emission are likely regulated at the level of
      transcript.

PMID- 15516503
TI  - Molecular physiological analysis of the two plastidic ATP/ADP transporters from
      Arabidopsis.
AB  - Arabidopsis (Arabidopsis thaliana) possesses two isoforms of plastidic ATP/ADP
      transporters (AtNTT1 and AtNTT2) exhibiting similar biochemical properties. To
      analyze the function of both isoforms on the molecular level, we examined the
      expression pattern of both genes by northern-blot analysis and promoter-beta
      glucuronidase fusions. AtNTT1 represents a sugar-induced gene mainly expressed in
      stem and roots, whereas AtNTT2 is expressed in several Arabidopsis tissues with
      highest accumulation in developing roots and young cotyledons. Developing lipid
      storing seeds hardly contained AtNTT1 or -2 transcripts. The absence of a
      functional AtNTT1 gene affected plant development only slightly, whereas AtNTT2T
      DNA, AtNTT1-2T-DNA, and RNA interference (RNAi) plants showed retarded plant
      development, mainly characterized by a reduced ability to generate primary roots
      and a delayed chlorophyll accumulation in seedlings. Electron microscopic
      examination of chloroplast substructure also revealed an impaired formation of
      thylakoids in RNAi seedlings. Moreover, RNAi- and AtNTT1-2T-DNA plants showed
      reduced accumulation of the nuclear-encoded protein CP24 during deetiolation.
      Under short-day conditions reduced plastidic ATP import capacity correlates with
      a substantially reduced plant growth rate. This effect is absent under long-day
      conditions, strikingly indicating that nocturnal ATP import into chloroplasts is
      important. Plastidic ATP/ADP transport activity exerts significant control on
      lipid synthesis in developing Arabidopsis seeds. In total we made the surprising
      observation that plastidic ATP/ADP transport activity is not required to pass
      through the complete plant life cycle. However, plastidic ATP/ADP-transporter
      activity is required for both an undisturbed development of young tissues and a
      controlled cellular metabolism in mature leaves.

PMID- 15516504
TI  - Profiling of oligolignols reveals monolignol coupling conditions in lignifying
      poplar xylem.
AB  - Lignin is an aromatic heteropolymer, abundantly present in the walls of secondary
      thickened cells. Although much research has been devoted to the structure and
      composition of the polymer to obtain insight into lignin polymerization, the low
      molecular weight oligolignol fraction has escaped a detailed characterization.
      This fraction, in contrast to the rather inaccessible polymer, is a simple and
      accessible model that reveals details about the coupling of monolignols, an issue
      that has raised considerable controversy over the past years. We have profiled
      the methanol-soluble oligolignol fraction of poplar (Populus spp.) xylem, a
      tissue with extensive lignification. Using liquid chromatography-mass
      spectrometry, chemical synthesis, and nuclear magnetic resonance, we have
      elucidated the structures of 38 compounds, most of which were dimers, trimers,
      and tetramers derived from coniferyl alcohol, sinapyl alcohol, their aldehyde
      analogs, or vanillin. All structures support the recently challenged random
      chemical coupling hypothesis for lignin polymerization. Importantly, the
      structures of two oligomers, each containing a gamma-p-hydroxybenzoylated
      syringyl unit, strongly suggest that sinapyl p-hydroxybenzoate is an authentic
      precursor for lignin polymerization in poplar.

PMID- 15516505
TI  - ARIA, an Arabidopsis arm repeat protein interacting with a transcriptional
      regulator of abscisic acid-responsive gene expression, is a novel abscisic acid
      signaling component.
AB  - Arabidopsis (Arabidopsis thaliana) genome contains more than 90 armadillo (arm)
      repeat proteins. However, their functions are largely unknown. Here, we report
      that an Arabidopsis arm repeat protein is involved in abscisic acid (ABA)
      response. We carried out two-hybrid screens to identify signaling components that
      modulate ABA-responsive gene expression. Employing a transcription factor, ABF2,
      which controls the ABA-dependent gene expression via the G-box type ABA
      responsive elements, we isolated an arm repeat protein. The ABF2-interacting
      protein, designated as ARIA (arm repeat protein interacting with ABF2), has
      another conserved sequence motif, BTB/POZ (broad complex, tramtrak, and bric-a
      brac/poxvirus and zinc finger) domain, in the C-terminal region. The
      physiological relevance of ABF2-ARIA interaction was supported by their similar
      expression patterns and similar subcellular localization. Plants overexpressing
      ARIA are hypersensitive to ABA and high osmolarity during germination and
      insensitive to salt during subsequent seedling growth. By contrast, an ARIA
      knockout mutant exhibits ABA and glucose insensitivities. Changes in the
      expression levels of several ABF2-regulated genes were also observed in ARIA
      overexpression lines, indicating that ARIA modulates the transcriptional activity
      of ABF2. Together, our data indicate that ARIA is a positive regulator of ABA
      response.

PMID- 15516506
TI  - nip, a symbiotic Medicago truncatula mutant that forms root nodules with aberrant
      infection threads and plant defense-like response.
AB  - To investigate the legume-Rhizobium symbiosis, we isolated and studied a novel
      symbiotic mutant of the model legume Medicago truncatula, designated nip
      (numerous infections and polyphenolics). When grown on nitrogen-free media in the
      presence of the compatible bacterium Sinorhizobium meliloti, the nip mutant
      showed nitrogen deficiency symptoms. The mutant failed to form pink nitrogen
      fixing nodules that occur in the wild-type symbiosis, but instead developed small
      bump-like nodules on its roots that were blocked at an early stage of
      development. Examination of the nip nodules by light microscopy after staining
      with X-Gal for S. meliloti expressing a constitutive GUS gene, by confocal
      microscopy following staining with SYTO-13, and by electron microscopy revealed
      that nip initiated symbiotic interactions and formed nodule primordia and
      infection threads. The infection threads in nip proliferated abnormally and very
      rarely deposited rhizobia into plant host cells; rhizobia failed to differentiate
      further in these cases. nip nodules contained autofluorescent cells and
      accumulated a brown pigment. Histochemical staining of nip nodules revealed this
      pigment to be polyphenolic accumulation. RNA blot analyses demonstrated that nip
      nodules expressed only a subset of genes associated with nodule organogenesis, as
      well as elevated expression of a host defense-associated phenylalanine ammonia
      lyase gene. nip plants were observed to have abnormal lateral roots. nip plant
      root growth and nodulation responded normally to ethylene inhibitors and
      precursors. Allelism tests showed that nip complements 14 other M. truncatula
      nodulation mutants but not latd, a mutant with a more severe nodulation phenotype
      as well as primary and lateral root defects. Thus, the nip mutant defines a new
      locus, NIP, required for appropriate infection thread development during invasion
      of the nascent nodule by rhizobia, normal lateral root elongation, and normal
      regulation of host defense-like responses during symbiotic interactions.

PMID- 15516508
TI  - AtGA3ox2, a key gene responsible for bioactive gibberellin biosynthesis, is
      regulated during embryogenesis by LEAFY COTYLEDON2 and FUSCA3 in Arabidopsis.
AB  - Embryonic regulators LEC2 (LEAFY COTYLEDON2) and FUS3 (FUSCA3) are involved in
      multiple aspects of Arabidopsis (Arabidopsis thaliana) seed development,
      including repression of leaf traits and premature germination and activation of
      seed storage protein genes. In this study, we show that gibberellin (GA) hormone
      biosynthesis is regulated by LEC2 and FUS3 pathways. The level of bioactive GAs
      is increased in immature seeds of lec2 and fus3 mutants relative to wild-type
      level. In addition, we show that the formation of ectopic trichome cells on lec2
      and fus3 embryos is a GA-dependent process as in true leaves, suggesting that the
      GA pathway is misactivated in embryonic mutants. We next demonstrate that the GA
      biosynthesis gene AtGA3ox2, which encodes the key enzyme AtGA3ox2 that catalyzes
      the conversion of inactive to bioactive GAs, is ectopically activated in embryos
      of the two mutants. Interestingly, both beta-glucuronidase reporter gene
      expression and in situ hybridization indicate that FUS3 represses AtGA3ox2
      expression mainly in epidermal cells of embryo axis, which is distinct from
      AtGA3ox2 pattern at germination. Finally, we show that the FUS3 protein
      physically interacts with two RY elements (CATGCATG) present in the AtGA3ox2
      promoter. This work suggests that GA biosynthesis is directly controlled by
      embryonic regulators during Arabidopsis embryonic development.

PMID- 15516507
TI  - Downstream divergence of the ethylene signaling pathway for harpin-stimulated
      Arabidopsis growth and insect defense.
AB  - Ethylene (ET) signal transduction may regulate plant growth and defense,
      depending on which components are recruited into the pathway in response to
      different stimuli. We report here that the ET pathway controls both insect
      resistance (IR) and plant growth enhancement (PGE) in Arabidopsis (Arabidopsis
      thaliana) plants responding to harpin, a protein produced by a plant pathogenic
      bacterium. PGE may result from spraying plant tops with harpin or by soaking
      seeds in harpin solution; the latter especially enhances root growth. Plants
      treated similarly develop resistance to the green peach aphid (Myzus persicae).
      The salicylic acid pathway, although activated by harpin, does not lead to PGE
      and IR. By contrast, PGE and IR are induced in both wild-type plants and
      genotypes that have defects in salicylic acid signaling. In response to harpin,
      levels of jasmonic acid (JA) decrease, and the COI1 gene, which is indispensable
      for JA signal transduction, is not expressed in wild-type plants. However, PGE
      and IR are stimulated in the JA-resistant mutant jar1-1. In the wild type, PGE
      and IR develop coincidently with increases in ET levels and the expression of
      several genes essential for ET signaling. The ET receptor gene ETR1 is required
      because both phenotypes are arrested in the etr1-1 mutant. Consistently,
      inhibition of ET perception nullifies the induction of both PGE and IR. The
      signal transducer EIN2 is required for IR, and EIN5 is required for PGE because
      IR and PGE are impaired correspondingly in the ein2-1 and ein5-1 mutants.
      Therefore, harpin activates ET signaling while conscribing EIN2 and EIN5 to
      confer IR and PGE, respectively.

PMID- 15516509
TI  - Investigations into the role of the plastidial peptide methionine sulfoxide
      reductase in response to oxidative stress in Arabidopsis.
AB  - Peptidyl Met residues are readily oxidized by reactive oxygen species to form Met
      sulfoxide. The enzyme peptide Met sulfoxide reductase (PMSR) catalyzes the
      reduction of Met sulfoxides back to Met. In doing so, PMSR is proposed to act as
      a last-chance antioxidant, repairing proteins damaged from oxidative stress. To
      assess the role of this enzyme in plants, we generated multiple transgenic lines
      with altered expression levels of the plastid form of PMSR (PMSR4). In transgenic
      plants, PMSR4 expression ranged from 95% to 40% (antisense) and more than 600%
      (overexpressing lines) of wild-type plants. Under optimal growing conditions,
      there is no effect of the transgene on the phenotype of the plants. When exposed
      to different oxidative stress conditions-methyl viologen, ozone, and high light
      differences were observed in the rate of photosynthesis, the maximum quantum
      yield (Fv/Fm ratio), and the Met sulfoxide content of the isolated chloroplast.
      Plants that overexpressed PMSR4 were more resistant to oxidative damage localized
      in the chloroplast, and plants that underexpressed PMSR4 were more susceptible.
      The Met sulfoxide levels in proteins of the soluble fraction of chloroplasts were
      increased by methyl viologen and ozone, but not by high-light treatment. Under
      stress conditions, the overexpression of PMSR4 lowered the sulfoxide content and
      underexpression resulted in an overall increase in content.

PMID- 15516511
TI  - Processes modulating calcium distribution in citrus leaves. An investigation
      using x-ray microanalysis with strontium as a tracer.
AB  - Citrus leaves accumulate large amounts of calcium that must be compartmented
      effectively to prevent stomatal closure by extracellular Ca2+ and interference
      with Ca(2+)-based cell signaling pathways. Using x-ray microanalysis, the
      distribution of calcium between vacuoles in different cell types of leaves of
      rough lemon (Citrus jambhiri Lush.) was investigated. Calcium was accumulated
      principally in palisade, spongy mesophyll, and crystal-containing idioblast
      cells. It was low in epidermal and bundle sheath cells. Potassium showed the
      reverse distribution. Rubidium and strontium were used as tracers to examine the
      pathways by which potassium and calcium reached these cells. Comparisons of
      strontium and calcium distribution indicated that strontium is a good tracer for
      calcium, but rubidium did not mirror the potassium distribution pattern. The
      amount of strontium accumulated was highest in palisade cells, lowest in bundle
      sheath and epidermal cells, and intermediate in the spongy mesophyll.
      Accumulation of strontium in palisade and spongy mesophyll was accompanied by
      loss of potassium from these cells and its accumulation in the bundle sheath.
      Strontium moved apoplastically from the xylem to all cell types, and manipulation
      of water loss from the adaxial leaf surface suggested that diffusion is
      responsible for strontium movement to this side of the leaf. The results
      highlight the importance of palisade and spongy mesophyll as repositories for
      calcium and suggest that calcium distribution between different cell types is the
      result of differential rates of uptake. This tracer technique can provide
      important information about the ion uptake and accumulation properties of cells
      in intact leaves.

PMID- 15516510
TI  - Citrate-permeable channels in the plasma membrane of cluster roots from white
      lupin.
AB  - White lupin (Lupinus albus) is well adapted to phosphorus deficiency by
      developing cluster roots that release large amounts of citrate into the
      rhizosphere to mobilize the sparingly soluble phosphorus. To determine the
      mechanism underlying citrate release from cluster roots, we isolated protoplasts
      from different types of roots of white lupin plants grown in phosphorus-replete
      (+P) and phosphorus-deficient (-P) conditions and used the patch-clamp technique
      to measure the whole-cell currents flowing across plasma membrane of these
      protoplasts. Two main types of anion conductance were observed in protoplasts
      prepared from cluster root tissue: (1) an inwardly rectifying anion conductance
      (IRAC) activated by membrane hyperpolarization, and (2) an outwardly rectifying
      anion conductance (ORAC) that became more activated with membrane depolarization.
      Although ORAC was an outward rectifier, it did allow substantial inward current
      (anion efflux) to occur. Both conductances showed citrate permeability, with IRAC
      being more selective for citrate3- than Cl- (PCit/PCl = 26.3), while ORAC was
      selective for Cl- over citrate (PCl/PCit = 3.7). Both IRAC and ORAC were
      sensitive to the anion channel blocker anthracene-9-carboxylic acid. These
      currents were also detected in protoplasts derived from noncluster roots of -P
      plants, as well as from normal (noncluster) roots of plants grown with 25 microm
      phosphorus (+P). No differences were observed in the magnitude or frequency of
      IRAC and ORAC currents between the cluster roots and noncluster roots of -P
      plants. However, the IRAC current from +P plants occurred less frequently than in
      the -P plants. IRAC was unaffected by external phosphate, but ORAC had reduced
      inward current (anion efflux) when phosphate was present in the external medium.
      Our data suggest that IRAC is the main pathway for citrate efflux from white
      lupin roots, but ORAC may also contribute to citrate efflux.

PMID- 15516513
TI  - Identification of Thlaspi caerulescens genes that may be involved in heavy metal
      hyperaccumulation and tolerance. Characterization of a novel heavy metal
      transporting ATPase.
AB  - Thlaspi caerulescens is a heavy metal hyperaccumulator plant species that is able
      to accumulate extremely high levels of zinc (Zn) and cadmium (Cd) in its shoots
      (30,000 microg g(-1) Zn and 10,000 microg g(-1) Cd), and has been the subject of
      intense research as a model plant to gain a better understanding of the
      mechanisms of heavy metal hyperaccumulation and tolerance and as a source of
      genes for developing plant species better suited for the phytoremediation of
      metal-contaminated soils. In this study, we report on the results of a yeast
      (Saccharomyces cerevisae) complementation screen aimed at identifying candidate
      heavy metal tolerance genes in T. caerulescens. A number of Thlaspi genes that
      conferred Cd tolerance to yeast were identified, including possible metal-binding
      ligands from the metallothionein gene family, and a P-type ATPase that is a
      member of the P1B subfamily of purported heavy metal-translocating ATPases. A
      detailed characterization of the Thlaspi heavy metal ATPase, TcHMA4, demonstrated
      that it mediates yeast metal tolerance via active efflux of a number of different
      heavy metals (Cd, Zn, lead [Pb], and copper [Cu]) out of the cell. However, in T.
      caerulescens, based on differences in tissue-specific and metal-responsive
      expression of this transporter compared with its homolog in Arabidopsis
      (Arabidopsis thaliana), we suggest that it may not be involved in metal
      tolerance. Instead, we hypothesize that it may play a role in xylem loading of
      metals and thus could be a key player in the hyperaccumulation phenotype
      expressed in T. caerulescens. Additionally, evidence is presented showing that
      the C terminus of the TcHMA4 protein, which contains numerous possible heavy
      metal-binding His and Cys repeats residues, participates in heavy metal binding.
      When partial peptides from this C-terminal domain were expressed in yeast, they
      conferred an extremely high level of Cd tolerance and Cd hyperaccumulation. The
      possibilities for enhancing the metal tolerance and phytoremediation potential of
      higher plants via expression of these metal-binding peptides are also discussed.

PMID- 15516512
TI  - LIN, a Medicago truncatula gene required for nodule differentiation and
      persistence of rhizobial infections.
AB  - Ethyl methanesulfonate mutagenesis of the model legume Medicago truncatula has
      previously identified several genes required for early steps in nodulation. Here,
      we describe a new mutant that is defective in intermediate steps of nodule
      differentiation. The lin (lumpy infections) mutant is characterized by a 4-fold
      reduction in the number of infections, all of which arrest in the root epidermis,
      and by nodule primordia that initiate normally but fail to mature. Genetic
      analyses indicate that the symbiotic phenotype is conferred by a single gene that
      maps to the lower arm of linkage group 1. Transcriptional markers for early Nod
      factor responses (RIP1 and ENOD40) are induced in lin, as is another early
      nodulin, ENOD20, a gene expressed during the differentiation of nodule primordia.
      By contrast, other markers correlated with primordium differentiation (CCS52A),
      infection progression (MtN6), or nodule morphogenesis (ENOD2 and ENOD8) show
      reduced or no induction in homozygous lin individuals. Taken together, these
      results suggest that LIN functions in maintenance of rhizobial infections and
      differentiation of nodules from nodule primordia.

PMID- 15516514
TI  - Maize starch-branching enzyme isoforms and amylopectin structure. In the absence
      of starch-branching enzyme IIb, the further absence of starch-branching enzyme Ia
      leads to increased branching.
AB  - Previous studies indicated that the deficiency of starch-branching enzyme (SBE)
      Ia in the single mutant sbe1a::Mu (sbe1a) has no impact on endosperm starch
      structure, whereas the deficiency of SBEIIb in the ae mutant is well known to
      reduce the branching of starch. We hypothesized that in maize (Zea mays)
      endosperm, the function of SBEIIb is predominant to that of SBEIa, and SBEIa
      would have an observable effect only on amylopectin structure in the absence of
      SBEIIb. To test this hypothesis, the mutant sbe1a was introgressed into lines
      containing either wx (lacking the granule-bound starch synthase GBSSI) or ae wx
      (lacking both SBEIIb and GBSSI) in the W64A background. Both western blotting and
      zymogram analysis confirmed the SBEIa deficiency in sbe1a wx and sbe1a ae wx, and
      the SBEIIb deficiency in ae wx and sbe1a ae wx. Using zymogram analysis, no
      pleiotropic effects of sbe1a genes on SBEIIa, starch synthase, or starch
      debranching enzyme isoforms were observed. High-performance size exclusion
      chromatography analysis shows that the chain-length profiles of amylopectin as
      well as beta-limit dextrin were indistinguishable between wx and sbe1a wx,
      whereas significant differences for both were observed between ae wx and sbe1a ae
      wx, suggesting an effect of SBEIa on amylopectin biosynthesis that is observable
      only in the absence of SBEIIb. The amylopectin branch density and the average
      number of branches per cluster were both higher in endosperm starch from sbe1a ae
      wx than from ae wx. These results indicate possible functional interactions
      between SBE isoforms that may involve enzymatic inhibition. Both the cluster
      repeat distance and the distance between branch points on the short intracluster
      chains were similar for all genotypes however, suggesting a similar pattern of
      individual SBE isoforms in cluster initiation and the determination of branch
      point location.

PMID- 15516515
TI  - Circadian rhythms of ethylene emission in Arabidopsis.
AB  - Ethylene controls multiple physiological processes in plants, including cell
      elongation. Consequently, ethylene synthesis is regulated by internal and
      external signals. We show that a light-entrained circadian clock regulates
      ethylene release from unstressed, wild-type Arabidopsis (Arabidopsis thaliana)
      seedlings, with a peak in the mid-subjective day. The circadian clock drives the
      expression of multiple ACC SYNTHASE genes, resulting in peak RNA levels at the
      phase of maximal ethylene synthesis. Ethylene production levels are tightly
      correlated with ACC SYNTHASE 8 steady-state transcript levels. The expression of
      this gene is controlled by light, by the circadian clock, and by negative
      feedback regulation through ethylene signaling. In addition, ethylene production
      is controlled by the TIMING OF CAB EXPRESSION 1 and CIRCADIAN CLOCK ASSOCIATED 1
      genes, which are critical for all circadian rhythms yet tested in Arabidopsis.
      Mutation of ethylene signaling pathways did not alter the phase or period of
      circadian rhythms. Mutants with altered ethylene production or signaling also
      retained normal rhythmicity of leaf movement. We conclude that circadian rhythms
      of ethylene production are not critical for rhythmic growth.

PMID- 15516516
TI  - Phloem loading. A reevaluation of the relationship between plasmodesmatal
      frequencies and loading strategies.
AB  - The incidence of plasmodesmata in the minor vein phloem of leaves varies widely
      between species. On this basis, two pathways of phloem loading have been
      proposed: symplastic where frequencies are high, and apoplastic where they are
      low. However, putative symplastic-loading species fall into at least two
      categories. In one, the plants translocate raffinose-family oligosaccharides
      (RFOs). In the other, the primary sugar in the phloem sap is sucrose (Suc). While
      a thermodynamically feasible mechanism of symplastic loading has been postulated
      for species that transport RFOs, no such mechanism is known for Suc transporters.
      We used p-chloromercuribenzenesulfonic acid inhibition of apoplastic loading to
      distinguish between the two pathways in three species that have abundant minor
      vein plasmodesmata and are therefore putative symplastic loaders. Clethra
      barbinervis and Liquidambar styraciflua transport Suc, while Catalpa speciosa
      transports RFOs. The results indicate that, contrary to the hypothesis that all
      species with abundant minor vein plasmodesmata load symplastically, C.
      barbinervis and L. styraciflua load from the apoplast. C. speciosa, being an RFO
      transporter, loads from the symplast, as expected. Data from these three species,
      and from the literature, also indicate that plants with abundant plasmodesmata in
      the minor vein phloem have abundant plasmodesmata between mesophyll cells. Thus,
      plasmodesmatal frequencies in the minor veins may be a reflection of overall
      frequencies in the lamina and may have limited relevance to phloem loading. We
      suggest that symplastic loading is restricted to plants that translocate
      oligosaccharides larger than Suc, such as RFOs, and that other plants, no matter
      how many plasmodesmata they have in the minor vein phloem, load via the apoplast.

PMID- 15516517
TI  - Plastid regulation of Lhcb1 transcription in the chlorophyte alga Dunaliella
      tertiolecta.
AB  - We identify four novel DNA-binding complexes in the nuclear-encoded Lhcb1
      promoter of the chlorophyte alga Dunaliella tertiolecta that are regulated by
      photosynthetic pathways in the plastid. The binding activities of three of the
      complexes were positively correlated with time-dependent changes in Lhcb1
      transcript abundance, implicating their roles as transcriptional enhancers in a
      retrograde signal transduction pathway. Using a combination of inhibitors,
      uncouplers, and antimycin A, and by following the kinetic pattern of gene
      regulation, we infer two different sensors in the signal transduction pathway. On
      short time scales of 0.5 to about 4 h, the transthylakoid membrane potential
      appears to be a critical determinant of gene expression, whereas on time scales
      of 8 h or longer, the redox state of the plastoquinone pool becomes increasingly
      more important. The differentiation of these two types of signals was observed in
      parallel effects on gene transcription and on the patterns of DNA-binding
      activities in the Lhcb1 promoter. These signals appear to be transduced at the
      nuclear level via a coordinated ensemble of DNA-binding complexes located between
      -367 and -188 bp from the start codon of the gene. The regulation of these
      elements allows the cell to up- or down-regulate the expression on Lhcb1 in
      response to changes in irradiance.

PMID- 15516518
TI  - A ring of negative charges in the intracellular vestibule of Kir2.1 channel
      modulates K+ permeation.
AB  - The glutamate at site 224 of a Kir2.1 channel plays an important role in K+
      permeation. The single-channel inward current flickers with reduced conductance
      in an E224G mutant. We show that open-channel fluctuations can also be observed
      in E224C, E224K, and E224Q mutants. Yet, open-channel fluctuations were not
      observed in either the wild-type or an E224D mutant. Introducing a negatively
      charged methanethiosulfonate reagent to the E224C mutant irreversibly increased
      channel conductance and eliminated open-channel fluctuations. These results
      suggest that although the negatively charged residue 224 is located at the
      internal vestibule, it is important for smooth inward K+ conduction. We
      identified a substate in the E224G mutant and showed that open-channel
      fluctuations are mainly attributed to rapid transitions between the substate and
      the main state. Also, we characterized the voltage- and ion-dependence of the
      substate kinetics. The open-channel fluctuations decreased in internal NH4+ or
      Tl+ as compared to internal K+. These results suggest that NH4+ and Tl+ gate the
      E224G mutant in a more stable state. Based on an ion-conduction model, we propose
      that the appearance of the substate in the E224G mutant is due to changes of ion
      gating in association with variations of ion-ion interaction in the permeation
      pathway.

PMID- 15516519
TI  - Fluorescent cargo proteins in pancreatic beta-cells: design determines secretion
      kinetics at exocytosis.
AB  - We compared secretion kinetics for four different fluorescent cargo proteins,
      each targeted to the lumen of insulin secretory vesicles. Upon stimulation,
      individual vesicles displayed one of four distinct patterns of fluorescence
      change: i), disappearance, ii), dimming, iii), transient brightening, or iv),
      persistent brightening. For each fusion protein, a different pattern of
      fluorescence change dominated. Furthermore, we demonstrated that the dominant
      pattern depends upon both i), the specific choice of fluorescent protein, and
      ii), the sequence of amino acids linking the cargo protein to the fluorescent
      protein. Thus, in beta-cells, experiments involving fluorescent cargo proteins
      for the study of exocytosis must be interpreted carefully, as design of a
      fluorescent cargo protein determines secretion kinetics at exocytosis.

PMID- 15516520
TI  - Structural transition of bacteriorhodopsin is preceded by deprotonation of Schiff
      base: microsecond time-resolved x-ray diffraction study of purple membrane.
AB  - The structural changes in the photoreaction cycle of bacteriorhodopsin, a light
      driven proton pump, was investigated at a resolution of 7 angstroms by a time
      resolved x-ray diffraction experiment utilizing synchrotron x rays from an
      undulator of SPring-8. The x-ray diffraction measurement system, used in coupling
      with a pulsed YAG laser, enabled us to record a diffraction pattern from purple
      membrane film at a time-resolution of 6 micros over the time domain of 5 micros
      to 500 ms. In the time domain, the functionally most important M-intermediate
      appears. A series of time-resolved x-ray diffraction data after photo-excitation
      showed clear intensity changes caused by the conformational changes of helix G in
      the M-intermediate. The population of the reaction intermediate was prominently
      observed at approximately 5 ms after a photo-stimulus. In contrast, absorption
      measurement indicated the deprotonation of the Schiff base predominantly occurred
      at approximately 300 micros after a photo-stimulus. These results showed that the
      conformational changes characterizing structurally the M-intermediate
      predominantly occur at a later stage of the deprotonation of the Schiff base.
      Thus, the M-intermediate can be divided into two metastable stages with different
      physical characteristics.

PMID- 15516522
TI  - The interpretation of current-clamp recordings in the cell-attached patch-clamp
      configuration.
AB  - In these experiments we have investigated the feasibility and accuracy of
      recording steady-state and dynamic changes in transmembrane potential
      noninvasively across an intact cell-attached patch using the current-clamp mode
      of a conventional patch-clamp amplifier. Using an equivalent circuit mimicking
      simultaneous whole-cell voltage-clamp and cell-attached current-clamp recordings
      we have defined both mathematically and experimentally the relationship between
      the membrane patch resistance, the seal resistance, and the fraction of the whole
      cell potential recorded across an intact membrane patch. This analysis revealed a
      steep increase in the accuracy of recording of steady-state membrane potential as
      the seal/membrane ratio increases from 0. The recording accuracy approaches 100%
      as the seal/membrane ratio approaches infinity. Membrane potential measurements
      across intact cell-attached patches in rat basophilic leukemia cells and rat
      megakaryocytes revealed a surprisingly high degree of accuracy and demonstrated
      the ability of this noninvasive technique to follow dynamic changes in potential
      in nonexcitable cells.

PMID- 15516521
TI  - Hindered convection of macromolecules in hydrogels.
AB  - Hindered convection of macromolecules in gels was studied by measuring the
      sieving coefficient (theta) of narrow fractions of Ficoll (Stokes-Einstein
      radius, r(s) = 2.7-5.9 nm) in agarose and agarose-dextran membranes, along with
      the Darcy permeability (kappa). To provide a wide range of kappa, varying amounts
      of dextran (volume fractions < or = 0.011) were covalently attached to agarose
      gels with volume fractions of 0.040 or 0.080. As expected, theta decreased with
      increasing r(s) or with increasing concentrations of either agarose or dextran.
      For each molecular size, theta plotted as a function of kappa fell on a single
      curve for all gel compositions studied. The dependence of theta on kappa and r(s)
      was predicted well by a hydrodynamic theory based on flow normal to the axes of
      equally spaced, parallel fibers. Values of the convective hindrance factor (K(c),
      the ratio of solute to fluid velocity), calculated from Theta and previous
      equilibrium partitioning data, were unexpectedly large; although K(c) < or = 1.1
      in the fiber theory, its apparent value ranged generally from 1.5 to 3. This
      seemingly anomalous result was explained on the basis of membrane heterogeneity.
      Convective hindrances in the synthetic gels were quite similar to those in
      glomerular basement membrane, when compared on the basis of similar solid volume
      fractions and values of kappa. Overall, the results suggest that convective
      hindrances can be predicted fairly well from a knowledge of kappa, even in
      synthetic or biological gels of complex composition.

PMID- 15516523
TI  - State-dependent changes in the electrostatic potential in the pore of a GluR
      channel.
AB  - The M2 loop and the M3 segment are the major pore-lining domains in the GluR
      channel. These domains determine ion permeation and channel block processes and
      are extensively involved in gating. To study the distribution of the membrane
      electric potential across the GluR channel pore, we recorded from alpha-amino-3
      hydroxy-5-methylisoxazole-4-proprionic acid receptors containing M2 and M3
      cysteine substitutions in the GluR-A subunit and measured the voltage dependence
      of the modification rate of these substituted cysteines by methanethiosulfonate
      reagents either in the presence or absence of glutamate. In the presence of
      glutamate, the voltage dependence became gradually stronger for positions located
      deeper in the pore suggesting that the electrostatic potential drops fairly
      uniformly across the pore in the open state. In contrast, in the absence of
      glutamate, the voltage dependence was biphasic. The difference in the
      electrostatic potential in the presence and absence of glutamate had an apparent
      maximum in the middle of the extracellular vestibule. We suggest that these state
      dependent changes in the membrane electric potential reflect a reorientation of
      the dipoles of the M2 loop alpha-helices toward and away from the center of the
      channel pore during gating.

PMID- 15516524
TI  - Kinetic pathways of beta-hairpin (un)folding in explicit solvent.
AB  - We examine the dynamical (un)folding pathways of the C-terminal beta-hairpin of
      protein G-B1 at room temperature in explicit solvent, by employing transition
      path sampling algorithms. The path ensembles contain information on the folding
      kinetics, including solvent motion. We determine the transition state ensembles
      for the two main transitions: 1), the hydrophobic collapse; and 2), the backbone
      hydrogen bond formation. In both cases the transition state ensembles are
      characterized by a layer (1) or a strip (2) of water molecules in between the two
      hairpin strands, supporting the hypothesis of the solvent as lubricant in the
      folding process. The transition state ensembles do not correspond with saddle
      points in the equilibrium free-energy landscapes. The kinetic pathways are thus
      not completely determined by the free-energy landscape. This phenomenon can occur
      if the order parameters obey different timescales. Using the transition interface
      sampling technique, we calculate the rate constants for (un)folding and find them
      in reasonable agreement with experiments, thus supporting the validation of using
      all-atom force fields to study protein folding.

PMID- 15516525
TI  - Cholesterol depletion suppresses the translational diffusion of class II major
      histocompatibility complex proteins in the plasma membrane.
AB  - Glycosylphosphatidylinositol (GPI)-linked and native major histocompatibility
      complex class II I-E(k) were used as probes to determine the effect of varying
      cholesterol concentration on the mobility of proteins in the plasma membrane.
      These proteins were imaged in Chinese hamster ovary cells using single-molecule
      fluorescence microscopy. Observed diffusion coefficients of both native and GPI
      linked I-E(k) proteins were found to depend on cholesterol concentration. As the
      cholesterol concentration decreases the diffusion coefficients decrease by up to
      a factor of 7 for native and 5 for GPI-linked I-E(k). At low cholesterol
      concentrations, after sphingomyelinase treatment, the diffusion coefficients are
      reduced by up to a factor of 60 for native and 190 for GPI-linked I-E(k). The
      effect is reversible on cholesterol reintroduction. Diffusion at all studied
      cholesterol concentrations, for both proteins, appears to be predominantly
      Brownian for time lags up to 2.5 s when imaged at 10 Hz. A decrease in diffusion
      coefficients is observed for other membrane proteins and lipid probes, DiIC12 and
      DiIC18. Fluorescence recovery after photobleaching measurements shows that the
      fraction of immobile lipid probe increases from 8 to approximately 40% after
      cholesterol extraction. These results are consistent with the previous work on
      cholesterol-phospholipid interactions. That is, cholesterol extraction destroys
      liquid cholesterol-phospholipid complexes, leaving solid-like high melting
      phospholipid domains that inhibit the lateral diffusion of membrane components.

PMID- 15516526
TI  - Intracellular axial current in Chara corallina reflects the altered kinetics of
      ions in cytoplasm under the influence of light.
AB  - Recent experiments demonstrate that the concentration of Ca2+ in cytoplasm of
      Chara corallina internodal cells plays important role in electrical excitation of
      the plasma membrane. The concentration of free Ca2+ in the cytoplasm -[Ca2+]c is
      also sensitive to visible light. Both phenomena were simultaneously studied by
      noninvasive measuring action potential (AP) and magnetic field with a
      superconducting quantum interference device magnetometer in very close vicinity
      of electrically excited internodal C. corallina cells. A temporal shift in the
      depolarization maximum, which progressively occurred after transferring cells
      from the dark into the light, can be explained by the extended Othmer model.
      Assuming that the change in membrane voltage during the depolarization part of AP
      is the direct consequence of an activation of [Ca2+]c sensitive Cl- channels, the
      model simulations compare well with the experimental data. We can say that we
      have an example of electrically elicited AP that is of biochemical nature.
      Electric and magnetic measurements are in good agreement.

PMID- 15516527
TI  - Structural features of a hyperthermostable endo-beta-1,3-glucanase in solution
      and adsorbed on "invisible" particles.
AB  - Conformational characteristics and the adsorption behavior of endo-beta-1,3
      glucanase from the hyperthermophilic microorganism Pyrococcus furiosus were
      studied by circular dichroism, steady-state and time-resolved fluorescence
      spectroscopy, and calorimetry in solution and in the adsorbed state. The
      adsorption isotherms were determined on two types of surfaces: hydrophobic Teflon
      and hydrophilic silica particles were specially designed so that they do not
      interact with light and therefore do not interfere with spectroscopic
      measurements. We present the most straightforward method to study structural
      features of adsorbed macromolecules in situ using common spectroscopic
      techniques. The enzyme was irreversibly adsorbed and immobilized in the adsorbed
      state even at high temperatures. Adsorption offered further stabilization to the
      heat-stable enzyme and in the case of adsorption on Teflon its denaturation
      temperature was measured at 133 degrees C, i.e., the highest experimentally
      determined for a protein. The maintenance of the active conformation and
      biological function particularly at high temperatures is important for
      applications in biocatalysis and biotechnology. With this study we also suggest
      that nature may employ adsorption as a complementary mode to maintain structural
      integrity of essential biomolecules at extreme conditions of temperature.

PMID- 15516528
TI  - Characterization of interaction between cationic lipid-oligonucleotide complexes
      and cellular membrane lipids using confocal imaging and fluorescence correlation
      spectroscopy.
AB  - Complexes formed by cationic liposomes and single-strand oligodeoxynucleotides
      (CL-ODN) are promising delivery systems for antisense therapy. ODN release from
      the complexes is an essential step for inhibiting activity of antisense drugs. We
      applied fluorescence correlation spectroscopy and confocal laser scanning
      microscopy to monitor CL-ODN complex interaction with membrane lipids leading to
      ODN release. To model cellular membranes we used giant unilamellar vesicles and
      investigated the transport of Cy-5-labeled ODNs across DiO-labeled membranes. For
      the first time, we directly observed that ODN molecules are transferred across
      the lipid bilayers and are kept inside the giant unilamellar vesicles after
      release from the carriers. ODN dissociation from the carrier was assessed by
      comparing diffusion constants of CL-ODN complexes and ODNs before complexation
      and after release. Freely diffusing Cy-5-labeled ODN (16-nt) has diffusion
      constant D(ODN) = 1.3 +/- 0.1 x 10(-6) cm2/s. Fluorescence correlation
      spectroscopy curves for CL-ODN complexes were fitted with two components, which
      both have significantly slower diffusion in the range of D(CL-ODN) =
      approximately 1.5 x 10(-8) cm2/s. Released ODN has the mean diffusion constant D
      = 1.1 +/- 0.2 x 10(-6) cm2/s, which signifies that ODN is dissociated from
      cationic lipids. In contrast to earlier studies, we report that
      phosphatidylethanolamine can trigger ODN release from the carrier in the full
      absence of anionic phosphatidylserine in the target membrane and that
      phosphatidylethanolamine-mediated release is as extensive as in the case of
      phosphatidylserine. The presented methodology provides an effective tool for
      probing a delivery potential of newly created lipid formulations of CL-ODN
      complexes for optimal design of carriers.

PMID- 15516529
TI  - Molecular mechanisms and kinetics between DNA and DNA binding ligands.
AB  - Mechanical properties of single double-stranded DNA (dsDNA) in the presence of
      different binding ligands were analyzed in optical-tweezers experiments with
      subpiconewton force resolution. The binding of ligands to DNA changes the overall
      mechanic response of the dsDNA molecule. This fundamental property can be used
      for discrimination and identification of different binding modes and,
      furthermore, may be relevant for various processes like nucleosome packing or
      applications like cancer therapy. We compared the effects of the minor groove
      binder distamycin-A, a major groove binding alpha-helical peptide, the
      intercalators ethidium bromide, YO-1, and daunomycin as well as the
      bisintercalator YOYO-1 on lambda-DNA. Binding of molecules to the minor and major
      groove of dsDNA induces distinct changes in the molecular elasticity compared to
      the free dsDNA detectable as a shift of the overstretching transition to higher
      forces. Intercalating molecules affect the molecular mechanics by a complete
      disappearance of the B-S transition and an associated increase in molecular
      contour length. Significant force hysteresis effects occurring during
      stretching/relaxation cycles with velocities >10 nm/s for YOYO-1 and >1000 nm/s
      for daunomycin. These indicate structural changes in the timescale of minutes for
      the YOYO-DNA and of seconds for the daunomycin-DNA complexes, respectively.

PMID- 15516530
TI  - Multiple-breath washout as a marker of lung disease in preschool children with
      cystic fibrosis.
AB  - Sensitive measures of lung function applicable to young subjects are needed to
      detect early cystic fibrosis (CF) lung disease. Forty children with CF aged 2 to
      5 years and 37 age-matched healthy control subjects performed multiple-breath
      inert gas washout, plethysmography, and spirometry. Thirty children in each group
      successfully completed all measures, with success on first visit being between 68
      and 86% for all three measures. Children with CF had significantly higher lung
      clearance index (mean [95% CI] difference for CF control 2.7 [1.9, 3.6], p <
      0.001) and specific airway resistance (1.65 z-scores [0.96, 2.33], p < 0.001),
      and significantly lower forced expired volume in 0.5 seconds (-0.49 z-scores [
      0.95, -0.03], p < 0.05). Abnormal lung function results were identified in 22
      (73%) of 30 children with CF by multiple-breath washout, compared with 14 (47%)
      of 30 by plethysmography, and 4 (13%) of 30 by spirometry. Children with CF who
      were infected with Pseudomonas aeruginosa had significantly higher lung clearance
      index, but no significant difference in other lung function measures, when
      compared with noninfected children. Most preschool children can perform multiple
      breath washout, plethysmography, and spirometry at first attempt. Multiple-breath
      washout detects abnormal lung function in children with CF more readily than
      plethysmography or spirometry.

PMID- 15516531
TI  - The prediction of small airway dimensions using computed tomography.
AB  - Chronic obstructive pulmonary disease is characterized by destruction of the lung
      parenchyma and/or small airway narrowing. To determine whether the dimensions of
      relatively large airways assessed using computed tomography (CT) reflect small
      airway dimensions measured histologically, we assessed these variables in
      nonobstructed or mild to moderately obstructed patients having lobar resection
      for a peripheral tumor. For both CT and histology, the square root of the airway
      wall area (Aaw) was plotted versus lumen perimeter to estimate wall thickness.
      The wall area percentage was calculated as wall area/lumen area + wall area x
      100. Although CT overestimated Aaw, the slopes of the relationships between the
      square root of Aaw and internal perimeter (Pi) measured with both techniques were
      related (CT slope = 0.2059 histology slope + 0.1701, R2 = 0.32, p < 0.01). The
      mean wall area percentage measured by CT for airways with a Pi of greater than
      0.75 cm predicted the mean dimensions of the small airways with an internal
      diameter of 1.27 mm (R2 = 0.57, p < 0.01). We conclude that CT measurements of
      airways with a Pi of 0.75 cm or more could be used to estimate the dimensions of
      the small conducting airways, which are the site of airway obstruction in chronic
      obstructive pulmonary disease.

PMID- 15516532
TI  - Sildenafil inhibits altitude-induced hypoxemia and pulmonary hypertension.
AB  - Exposure to high altitude induces pulmonary hypertension that may lead to life
      threatening conditions. In a randomized, double-blind, placebo-controlled study,
      the effects of oral sildenafil on altitude-induced pulmonary hypertension and gas
      exchange in normal subjects were examined. Twelve subjects (sildenafil [SIL] n =
      6; placebo [PLA] n = 6) were exposed for 6 days at 4,350 m. Treatment (3 x 40
      mg/day) was started 6 to 8 hours after arrival from sea level to high altitude
      and maintained for 6 days. Systolic pulmonary artery pressure (echocardiography)
      increased at high altitude before treatment (+29% versus sea level, p < 0.01),
      then normalized in SIL (-6% versus sea level, NS) and remained elevated in PLA
      (+21% versus sea level, p < 0.05). Pulmonary acceleration time decreased by 27%
      in PLA versus 6% in SIL (p < 0.01). Cardiac output and systemic blood pressures
      increased at high altitude then decreased similarly in both groups. Pa(O(2)) was
      higher and alveolar-arterial difference in O(2) lower in SIL than in PLA at rest
      and exercise (p < 0.05). The altitude-induced decrease in maximal O(2)
      consumption was smaller in SIL than in PLA (p < 0.05). Sildenafil protects
      against the development of altitude-induced pulmonary hypertension and improves
      gas exchange, limiting the altitude-induced hypoxemia and decrease in exercise
      performance.

PMID- 15516533
TI  - Brain-derived neurotrophic factor in platelets and airflow limitation in asthma.
AB  - Brain-derived neurotrophic factor (BDNF), a key mediator of neuronal plasticity,
      contributes to airway obstruction and hyperresponsiveness in a model of allergic
      asthma. BDNF is stored in human platelets and circulates in human plasma, but the
      significance of BDNF in this compartment is poorly understood. We investigated
      the relationship between platelet and plasma BDNF levels and pulmonary function
      in a cohort of 26 adult patients with recently diagnosed allergic asthma. BDNF
      levels in serum, platelets, and plasma were significantly increased in
      participants with asthma, as compared with 26 age- and sex-matched control
      subjects. In steroid-naive patients, but not in patients using inhaled
      corticosteroids, enhanced platelet BDNF levels correlated with parameters of
      airway obstruction and airway hyperresponsiveness to histamine. Experiments with
      activated peripheral blood mononuclear cells revealed that corticosteroids such
      as fluticasone effectively suppress BDNF secretion. In conclusion, we demonstrate
      that enhanced platelet BDNF is associated with airflow limitation and airway
      hyperresponsiveness in asthma. In addition, we provide evidence that
      corticosteroids suppress BDNF production by activated immune cells.

PMID- 15516534
TI  - Severe respiratory syncytial virus bronchiolitis in infancy and asthma and
      allergy at age 13.
AB  - We have prospectively studied wheezing disorder and allergy in 47 children
      hospitalized with respiratory syncytial virus (RSV) bronchiolitis in infancy and
      93 matched control subjects. Subjects with at least three episodes of wheezing
      were defined as recurrent wheezers and as having asthma if the episodes were
      doctor verified. Here we report the outcome at age 13 years in 46/47 children
      with RSV and 92/93 control subjects. Wheezing disorder and clinical allergy were
      estimated using a questionnaire. Skin prick tests were performed and serum IgE
      antibodies measured. Spirometry was undertaken at rest, after dry air challenge,
      and after beta2-agonist inhalation. The occurrence of symptoms over the previous
      12 months was significantly higher in the RSV group than among the control
      subjects, 43% versus 8% for asthma/recurrent wheezing and 39% versus 15% for
      allergic rhinoconjunctivitis. Sensitization to common inhaled allergens was more
      frequent in the RSV group than in the control subjects, judged by skin prick
      tests (50% versus 28%; p = 0.022), or by serum IgE antibodies (45% versus 26%; p
      = 0.038). Compared with the control subjects, the RSV group showed mild airway
      obstruction both at rest and after bronchodilation, and had slightly more
      reactive airways. RSV bronchiolitis in infancy severe enough to cause
      hospitalization is a risk factor for allergic asthma in early adolescence.

PMID- 15516535
TI  - Cumulative influence of organ dysfunctions and septic state on mortality of
      critically ill children.
AB  - The interaction between sepsis and multiple organ dysfunction syndrome is poorly
      defined in children. We analyzed by Cox regression models the cumulative
      influence of organ dysfunctions, using the pediatric logistic organ dysfunction
      (PELOD) score, and septic state (systemic inflammatory response syndrome or
      sepsis, severe sepsis, and septic shock) on mortality of critically ill children.
      We included 593 children (mortality rate: 8.6%) from three pediatric intensive
      care units; 514 patients had at least a systemic inflammatory response syndrome
      and 269 had two or more organ dysfunctions. Hazard ratio of death significantly
      increased with the severity of organ dysfunction, as estimated by the PELOD
      score, and the worst diagnostic category of septic state. Each increase of one
      unit in the PELOD score multiplied the hazard ratio by 1.096 (p < 0.0001); hazard
      ratio of diagnostic category was 9.039 (p = 0.031) for systemic inflammatory
      response syndrome or sepsis, 18.797 (p = 0.007) for severe sepsis and 32.572 (p <
      0.001) for septic shock. Cumulative hazard ratio of death = (hazard ratio of
      PELOD score) x (hazard ratio of diagnostic category). We conclude that there is a
      cumulative accrual of the risk of death both with an increasing severity of organ
      dysfunction and an increasing severity of the diagnostic category of septic
      state.

PMID- 15516536
TI  - Neuropeptide Y and leptin in patients with obstructive sleep apnea syndrome: role
      of obesity.
AB  - Neuropeptide Y (NPY) and leptin are two peptides involved in the regulation of
      body weight, energy balance, and sympathetic tone. This study investigates the
      independent role of apneas and obesity on NPY and leptin plasma levels in
      patients with obstructive sleep apnea syndrome (OSAS). To this end we compared
      their values in 23 obese (body mass index > 30 kg/m2) and 24 nonobese (body mass
      index < 27 kg/m2) patients with OSAS, and in 19 obese and 18 nonobese control
      subjects without OSAS. Patients who used continuous positive airway pressure for
      more than 4 hours/night were reexamined 3 and 12 months later. We found that NPY
      levels were increased (p < 0.01) in patients with OSAS independently of obesity.
      Leptin levels were also increased in OSAS but this was mostly associated to
      obesity. Continuous positive airway pressure treatment reduced NPY levels in all
      patients and leptin levels only in nonobese patients (p < 0.01). We concluded
      that NPY and leptin plasma levels are increased in patients with OSAS. Yet,
      whereas the former appear independent of obesity, the latter are mostly
      associated with obesity.

PMID- 15516537
TI  - Use of Sniff nasal-inspiratory force to predict survival in amyotrophic lateral
      sclerosis.
AB  - Respiratory muscle weakness is the usual cause of death in amyotrophic lateral
      sclerosis. The prognostic value of the forced vital capacity (FVC), mouth
      inspiratory force, and sniff nasal-inspiratory force were established in a group
      of 98 patients with amyotrophic lateral sclerosis who were followed trimonthly
      for 3 years. Sniff nasal-inspiratory force correlated with the transdiaphragmatic
      pressure (r = 0.9, p < 0.01). Sniff nasal-inspiratory force was most likely to be
      recorded at the last visit (96% of cases), compared with either the FVC or mouth
      inspiratory force (86% and 81%, respectively, p < 0.01). A sniff nasal
      inspiratory force less than 40 cm H(2)O was significantly related with nocturnal
      hypoxemia. When sniff nasal-inspiratory force was less than 40 cm H(2)O, the
      hazard ratio for death was 9.1 (p = 0.001), and the median survival was 6 +/- 0.3
      months. The sensitivity of FVC < 50% for predicting 6-month mortality was 58%
      with a specificity of 96%, whereas sniff nasal-inspiratory force less than 40
      H(2)O had a sensitivity of 97% and a specificity of 79% for death within 6
      months. Thus the sniff nasal-inspiratory force test is a good measure of
      respiratory muscle strength in amyotrophic lateral sclerosis, it can be performed
      by patients with advanced disease, and it gives prognostic information.

PMID- 15516539
TI  - Country of birth as a risk factor for asthma among Mexican Americans.
AB  - In the United States, among Hispanics, Mexican Americans have the lowest rate of
      asthma. However, this population includes Mexican Americans born in the United
      States and in Mexico, and risk factors that might impact the prevalence of asthma
      differ between these groups. To determine the prevalence of and risk factors for
      asthma among U.S.- and Mexican-born Mexican Americans, we analyzed data from two
      U.S. surveys that included 4,574 persons who self-reported their ethnicity as
      Mexican American from the Third National Health and Nutrition Examination Survey
      (NHANES III) 1998-1994 and 12,980 persons who self-reported their ethnicity as
      Mexican American from National Health Interview Survey (NHIS) 1997-2001. U.S.
      born Mexican Americans were more likely than Mexican-born Mexican Americans to
      report ever having asthma in both the NHANES III (7% [SE 0.5] vs. 3% [SE 0.3], p
      < 0.001) and NHIS surveys (8.1% [0.4] vs. 2.5% [0.2], p < 0.001). In a
      multivariate regression model controlling for multiple demographic variables and
      health care, the risk for asthma was higher among U.S.-born Mexicans in NHANES
      III (odds ratio 2.1, 95% confidence interval 1.4-3.3) and NHIS (odds ratio 2.7,
      95% confidence interval 1.6-5.5). In conclusion, the prevalence of asthma was
      higher in U.S.-born than in Mexican-born Mexican Americans. This finding
      highlights the importance of environmental exposures in developing asthma in a
      migratory population.

PMID- 15516538
TI  - Gene transfer of the Na+,K+-ATPase beta1 subunit using electroporation increases
      lung liquid clearance.
AB  - The development of nonviral methods for efficient gene transfer to the lung is
      highly desired for the treatment of several pulmonary diseases. We have developed
      a noninvasive procedure using electroporation to transfer genes to the lungs of
      rats. Purified plasmid (100-600 microg) was delivered to the lungs of
      anesthetized rats through an endotracheal tube, and a series of square-wave
      pulses were delivered via electrodes placed on the chest. Relatively uniform gene
      expression was observed in multiple cell types and layers throughout the lung,
      including airway and alveolar epithelial cells, airway smooth muscle cells, and
      vascular endothelial cells, and this finding was dose- and pulse length
      dependent. Most important, no inflammatory response was detected. To demonstrate
      efficacy of this approach, the beta1 subunit of the Na(+),K(+)-ATPase was
      transferred to the lungs of rats with or without electroporation, and 3 days
      later, alveolar fluid clearance was measured. Animals electroporated with the
      beta1 subunit plasmid showed a twofold increase in alveolar fluid clearance and
      Na(+),K(+)-ATPase activity as compared with animals receiving all other plasmids,
      with or without electroporation. These results demonstrate that electroporation
      is an effective method to increase clearance by introducing therapeutic genes
      (Na(+),K(+)-ATPase) into the rat lung.

PMID- 15516540
TI  - Antibiotic rotation and development of gram-negative antibiotic resistance.
AB  - To attain a better understanding of antibiotic cycling and its effects on the
      epidemiology of antibiotic resistance in gram-negative microorganisms, two
      different antibiotic classes (quinolone and beta-lactam) were cycled during four
      4-month periods in a surgical intensive care unit. Respiratory aspirates and
      rectal swabs were obtained and DNA fingerprinting was performed. Primary endpoint
      of the study was the acquisition rate with gram-negative bacteria resistant to
      the antibiotic of choice during each cycle. Secondary endpoints were changes in
      endemic prevalence of resistant bacteria and the relative importance of cross
      transmission. In all, 388 patients were included and 2,520 cultures analyzed.
      Adherence to antibiotic protocol was 96%. Overall antibiotic use increased with
      24%. Acquisition rates with resistant bacteria were highest during levofloxacin
      exposure (relative risk [RR] 3.2; 95% confidence interval [CI]: 1.4-7.1) and
      piperacillin/tazobactam exposure (RR 2.4; 95% CI 1.2-4.8). The relative
      importance of cross-transmission decreased during the study. For individual
      patients, treatment with levofloxacin was the only independent risk factor for
      acquisition of levofloxacin-resistant bacteria (hazard ratio 12.6; 95% CI 3.8
      41.6). Potential for selection of antibiotic-resistant gram-negative bacteria
      during periods of homogeneous exposure increased from cefpirome to
      piperacillin/tazobactam to levofloxacin. Cycling of homogeneous antibiotic
      exposure is unlikely to control the emergence of gram-negative antimicrobial
      resistance in intensive care units.

PMID- 15516541
TI  - Phenomenology, science and the anthropology of the self: a new model for the
      aetiology of psychosis.

PMID- 15516542
TI  - The aetiology of eating disorders.

PMID- 15516543
TI  - Association between prenatal exposure to analgesics and risk of schizophrenia.
AB  - BACKGROUND: Disturbances in the central nervous system originating during foetal
      life may increase the risk of schizophrenia. AIMS: To illuminate the hypothesis
      that prenatal exposure to analgesics may affect foetal neurodevelopment, leading
      to increased risk of schizophrenia in adulthood. METHOD: Using data from the
      Copenhagen Perinatal Cohort and from the Danish Psychiatric Central Register, we
      studied the relationship between prenatal exposure to analgesics and the risk of
      schizophrenia. The effect of prenatal exposure was adjusted for parental history
      of schizophrenia, second-trimester viral infections, concomitant drug treatment
      during pregnancy, an index of pregnancy complications, parental social status and
      parental age. RESULTS: In a risk set of 7999 individuals, 116 cases of
      schizophrenia were found (1.5%). Prenatal exposure to analgesics in the second
      trimester was associated with an elevated risk (adjusted odds ratio 4.75, 95%
      CI1.9-12.0). Independent of the covariates, the effect remained statistically
      significant. CONCLUSIONS: Independent of a wide range of possible confounders, a
      significant association between second-trimester exposure to analgesics and
      increased risk of schizophrenia was observed.

PMID- 15516544
TI  - Course of illness in depressive and bipolar disorders. Naturalistic study, 1994
      1999.
AB  - BACKGROUND: Newer antidepressants have increasingly been used during the past
      decade. These drugs may increase compliance and reduce the risk of cycle
      acceleration in affective disorders. AIMS: To investigate the naturalistic
      longitudinal course of illness in patients with depressive or bipolar disorder
      following the use of recently introduced drugs. METHOD: The rates of relapse
      leading to hospitalisation after successive episodes were calculated in a case
      register study including all hospital admissions of patients with primary
      affective disorder in Denmark during 1994-1999. Altogether, 9417 patients had a
      diagnosis of depressive disorder and 1106 patients had a diagnosis of mania or
      bipolar disorder, at first-ever discharge. RESULTS: The rate of relapse leading
      to hospitalisation increased with the number of previous episodes in both
      depressive and bipolar disorders. However, the effect of episodes was not
      significant for men. The rate of relapse did not decline during the study period.
      CONCLUSIONS: The course of severe depressive and bipolar disorders has remained
      roughly the same despite introduction of new treatments.

PMID- 15516545
TI  - Trends in service use and treatment for mental disorders in adults throughout
      Great Britain.
AB  - BACKGROUND: Trends in health treatments and outcomes in the general population
      may be used to monitor achievement of health targets. AIMS: To investigate
      changes in mental health services and treatment in Britain over a 7-year period.
      METHOD: National surveys of psychiatric morbidity were completed in 1993 and 2000
      in households throughout Great Britain. Standardised interviews were used to
      establish psychiatric case status and service and treatment utilisation in adults
      aged 16-64 years. RESULTS: Use of psychotropic medication doubled in those
      designated as psychiatric cases. In the non-case-status population antidepressant
      use rose from 0.16% in 1993 (95% CI 0.07-0.25) to 2.02% in 2000 (95% CI 1.69
      2.35). However, the overall prevalence of neurotic and psychotic disorder hardly
      changed from 1993 to 2000. Use of specialised 'talking treatments'did not
      increase significantly, except in the non-case group. CONCLUSIONS: Treatment with
      psychotropic medication alone is unlikely to improve the overall mental health of
      the nation. A policy based almost exclusively on treatment of identified cases
      should be augmented by preventive approaches.

PMID- 15516546
TI  - Factors influencing the development and amelioration of suicidal thoughts in the
      general population. Cohort study.
AB  - BACKGROUND: The incidence of suicidal thoughts in the British population is
      unknown. AIMS: To determine the factors associated with the development of, and
      recovery from, suicidal thoughts. METHOD: An 18-month follow-up survey
      investigated 2404 of the adults who took part in the second National Psychiatric
      Morbidity Survey. RESULTS: The annual incidence of suicidal thoughts was 2.3%.
      Incidence was highest in women and among 16- to 24-year-olds. Increased incidence
      was associated with not being in a stable relationship, low levels of social
      support and being unemployed. Fifty-seven per cent of those with suicidal
      thoughts at baseline had recovered by the 18-month follow-up interview.
      CONCLUSIONS: Risk factors for suicidal thoughts are similar to those for
      completed suicide, although the age and gender patterning is different. Fewer
      than 1 in 200 people who experience suicidal thoughts go on to complete suicide.
      Further study into explanations for the differences in the epidemiology of
      suicidal thoughts and suicide is crucial to understanding the pathways
      (protective and precipitating) linking suicidal thoughts to completed suicide and
      should help inform effective prevention of suicide.

PMID- 15516547
TI  - Homicide and mental illness in New Zealand, 1970-2000.
AB  - BACKGROUND: Homicides by mentally ill persons have led to political concerns
      about deinstitutionalisation. AIMS: To provide accurate information about the
      contribution of mental illness to homicide rates. METHOD: Retrospective study of
      homicide in New Zealand from 1970 to 2000, using data from government sources.
      'Mentally abnormal homicide'perpetrators were defined as those found unfitto
      stand trial, not guilty by reason of insanity, convicted and sentenced to
      psychiatric committal, or convicted of infanticide. Group and time trends were
      analysed. RESULTS: Mentally abnormal homicides constituted 8.7% of the 1498
      homicides. The annual rate of such homicides was 1.3 per million population,
      static over the period. Total homicides increased by over 6% per year from 1970
      to 1990, then declined from 1990 to 2000. The percentage of all homicides
      committed by the mentally abnormal group fell from 19.5% in 1970 to 5.0% in 2000.
      Ten percent of perpetrators had been admitted to hospital during the month before
      the offence; 28.6% had had no prior contact with mental health services. Victims
      were most commonly known to the perpetrator (74%). CONCLUSIONS:
      Deinstitutionalisation appears not to be associated with an increased risk of
      homicide by people who are mentally ill.

PMID- 15516548
TI  - Anxiety and the risk of death in older men and women.
AB  - BACKGROUND: There are inconsistent reports as to whether people with anxiety
      disorders have a higher mortality risk. AIMS: To determine whether anxiety
      disorders predict mortality in older men and women in the community. METHOD:
      Longitudinal data were used from a large, community-based random sample (n=3107)
      of older men and women (55-85 years) in The Netherlands, with a follow-up period
      of 7.5 years. Anxiety disorders were assessed according to DSM-III criteria in a
      two-stage screening design. RESULTS: In men, the adjusted mortality risk was 1.78
      (95% CI 1.01-3.13) in cases with diagnosed anxiety disorders at baseline. In
      women, no significant association was found with mortality. CONCLUSIONS: The
      study revealed a gender difference in the association between anxiety and
      mortality. For men, but not for women, an increased mortality risk was found for
      anxiety disorders.

PMID- 15516549
TI  - Quality of life and function after electroconvulsive therapy.
AB  - BACKGROUND: The National Institute for Clinical Excellence in the UK has
      recommended limiting the use of electroconvulsive therapy (ECT), partly because
      of the inadequacy of research into the effects of ECT on quality of life and
      function. AIMS: To examine the effects of ECT on function and quality of life,
      particularly as they relate to changes in mood and cognition in the month
      following this therapy. METHOD: We measured changes in quality of life, function,
      mood and cognition in a prospective sample of 77 depressed patients given ECT.
      RESULTS: All quality of life and function outcomes were improved at the 2-week
      and 4-week marks after ECT. Improvement in quality of life was related to mood,
      whereas improvement in instrumental activities of daily living function was
      related to improvement in global cognition. CONCLUSIONS: Electroconvulsive
      therapy is associated with early improvement in function and quality of life. A
      restrictive attitude towards this therapy is not warranted on the basis of its
      effects on quality of life and function.

PMID- 15516550
TI  - Adapting to the challenge of psychosis: personal resilience and the use of
      sealing-over (avoidant) coping strategies.
AB  - BACKGROUND: Avoidance coping (e.g. sealing over) is common in people recovering
      from psychosis, but it is not understood why some individuals 'seal over'. AIMS:
      We examined the hypothesis that individuals who 'seal over' do not have the
      personal resilience to withstand this major life event. METHOD: Fifty
      participants were interviewed during an acute episode of psychosis and reassessed
      at 3-month and 6-month follow-up. Measures included psychotic symptoms, recovery
      style, service engagement, parental and adult attachment and self-evaluative
      beliefs. RESULTS: Sealing-over recovery styles are associated with negative early
      childhood experience, insecure adult attachment, negative self-evaluative beliefs
      and insecure identity. Insecure adult attachment was associated with less
      engagement with services. CONCLUSIONS: Sealing over was associated with multiple
      signs of low personal resilience in adapting to psychosis.

PMID- 15516551
TI  - Minimal-contact psychotherapy for sub-threshold depression in primary care.
      Randomised trial.
AB  - BACKGROUND: Sub-threshold depression is a prognostic variable for major
      depression. Interventions in sub-threshold depression may prevent the onset of
      new cases of major depression. AIMS: To examine the effects of minimal-contact
      psychotherapy in primary care patients with sub-threshold depression on the onset
      of major depression, on the reduction in depressive symptoms and on health
      related quality of life. METHOD: We conducted a randomised trial in primary care,
      in which patients screened for sub-threshold depression were randomly assigned to
      minimal-contact psychotherapy (n=107) or to usual care (n=109). RESULTS: One year
      after baseline, the incidence of major depressive disorder was found to be
      significantly lower in the psychotherapy group (12%) than in those receiving
      usual care (18%). Small but significant effects were also found on depressive
      symptoms and on aspects of health-related quality of life. CONCLUSIONS: Primary
      care patients with sub-threshold depression can benefit from minimal-contact
      psychotherapy.

PMID- 15516552
TI  - Mental illness and accidental death. Case-control psychological autopsy study.
AB  - BACKGROUND: Few studies have systematically investigated the psychiatric
      antecedents of accidental death. AIMS: To examine the patterns of psychiatric
      morbidities contributing to accidental death in three ethnic groups (Han, Ami and
      Atayal) in Taiwan. METHOD: A case-control psychological autopsy was conducted
      among 90 accidental deaths (randomly selected from a total of 413) and 180 living
      controls matched for age, gender, ethnicity and area of residence in Taiwan.
      RESULTS: The risk of accidental death was significantly associated with alcohol
      use disorder and with other common mental disorders. When jointly considered, it
      was greatest when these two types of disorders co-existed, followed by common
      mental disorders alone. The risk of accidental death increased with the number of
      comorbid conditions. CONCLUSIONS: The prevention of accidental death should be
      incorporated into preventive psychiatry, not just for alcohol use disorder, but
      also for all other common mental disorders.

PMID- 15516553
TI  - Effects of education and culture on the validity of the Geriatric Mental State
      and its AGECAT algorithm.
AB  - BACKGROUND: The Geriatric Mental State (GMS) is the most widely used psychiatric
      research assessment for older persons. Evidence for validity comes from the
      developed world. AIMS: To assess the validity of GMS/AGECAT organicity and
      depression diagnoses in 26 centres in India, China, Latin America and Africa.
      METHOD: We studied 2941 persons aged 60 years and over: 742 people with dementia
      and three groups free of dementia (697 with depression, 719 with high and 783
      with low levels of education). Local clinicians diagnosed dementia (DSM-IV) and
      depression (Montgomery-Asberg Depression Rating Scale score >/=18). RESULTS: For
      dementia diagnosis GMS/AGECAT performed well in many centres but educational bias
      was evident. Specificity was poor in India and sensitivity sub-optimal in Latin
      America. A predictive algorithm excluding certain orientation items but including
      interviewer judgements improved upon the AGECAT algorithm. For depression,
      sensitivity was high. The EURO-D depression scale, derived from GMS items using
      European data, has a similar factor structure in Latin America, India and, to a
      lesser extent, China. CONCLUSIONS: Valid, comprehensive mental status assessment
      across cultures seems achievable in principle.

PMID- 15516554
TI  - Depression intervention in resource-poor regions.

PMID- 15516555
TI  - ADHD in developing countries.

PMID- 15516557
TI  - A little help from my friends: quality control of presecretory proteins in
      bacteria.

PMID- 15516558
TI  - Conserved region 2.1 of Escherichia coli heat shock transcription factor sigma32
      is required for modulating both metabolic stability and transcriptional activity.
AB  - Escherichia coli heat shock transcription factor sigma32 is rapidly degraded in
      vivo, with a half-life of about 1 min. A set of proteins that includes the DnaK
      chaperone team (DnaK, DnaJ, GrpE) and ATP-dependent proteases (FtsH, HslUV, etc.)
      are involved in degradation of sigma32. To gain further insight into the
      regulation of sigma32 stability, we isolated sigma32 mutants that were markedly
      stabilized. Many of the mutants had amino acid substitutions in the N-terminal
      half (residues 47 to 55) of region 2.1, a region highly conserved among bacterial
      sigma factors. The half-lives ranged from about 2-fold to more than 10-fold
      longer than that of the wild-type protein. Besides greater stability, the levels
      of heat shock proteins, such as DnaK and GroEL, increased in cells producing
      stable sigma32. Detailed analysis showed that some stable sigma32 mutants have
      higher transcriptional activity than the wild type. These results indicate that
      the N-terminal half of region 2.1 is required for modulating both metabolic
      stability and the activity of sigma32. The evidence suggests that sigma32
      stabilization does not result from an elevated affinity for core RNA polymerase.
      Region 2.1 may, therefore, be involved in interactions with the proteolytic
      machinery, including molecular chaperones.

PMID- 15516559
TI  - The Salmonella membrane protein IgaA modulates the activity of the RcsC-YojN-RcsB
      and PhoP-PhoQ regulons.
AB  - The Salmonella enterica serovar Typhimurium membrane protein IgaA and the PhoP
      PhoQ two-component system are used by this pathogen to attenuate the
      intracellular growth rate within fibroblasts. IgaA has also recently been shown
      to contribute to virulence by exerting tight repression of the RcsC-YojN-RcsB
      phosphorelay in host tissues. Here we show that loss of repression of the RcsC
      YojN-RcsB system, linked to an R188H mutation in the IgaA protein (igaA1 allele),
      is accompanied by altered expression of PhoP-PhoQ-activated (pag) genes. The
      changes in gene expression were different depending on the specific pag gene
      analyzed. Thus, transcription of ugd, which is required for lipopolysaccharide
      modification and colanic acid capsule synthesis, was enhanced in the igaA1
      mutant. RcsB and its coregulator RcsA promoted this alteration in a PhoP-PmrA
      independent manner. Unlike ugd, activation of the RcsC-YojN-RcsB phosphorelay
      negatively affected the expression of all other pag genes tested. In this case,
      RcsB alone was responsible for this effect. We also found that PhoP, but not
      PmrA, negatively modulates the expression of gmm, a gene required for colanic
      acid synthesis that is regulated positively by RcsC-YojN-RcsB. Finally, it was
      observed that the fine regulation of pag genes exerted by RcsB requires the RpoS
      protein and that an active RcsB, but not RcsA, diminishes expression of the phoP
      gene. These data support the hypothesis that in Salmonella there is an intimate
      regulatory circuit between the PhoP-PhoQ and RcsC-YojN-RcsB phosphorelays, which
      is revealed only when the RcsC-YojN-RcsB signaling route is derepressed.
      Consistent with the phenotypes observed in fibroblast cells, IgaA is predicted to
      favor expression of the entire PhoP-PhoQ regulon based on its repression of the
      RcsC-YojN-RcsB phosphorelay.

PMID- 15516560
TI  - Calcium inhibits bap-dependent multicellular behavior in Staphylococcus aureus.
AB  - Bap (biofilm-associated protein) is a 254-kDa staphylococcal surface protein
      implicated in formation of biofilms by staphylococci isolated from chronic
      mastitis infections. The presence of potential EF-hand motifs in the amino acid
      sequence of Bap prompted us to investigate the effect of calcium on the
      multicellular behavior of Bap-expressing staphylococci. We found that addition of
      millimolar amounts of calcium to the growth media inhibited intercellular
      adhesion of and biofilm formation by Bap-positive strain V329. Addition of
      manganese, but not addition of magnesium, also inhibited biofilm formation,
      whereas bacterial aggregation in liquid media was greatly enhanced by metal
      chelating agents. In contrast, calcium or chelating agents had virtually no
      effect on the aggregation of Bap-deficient strain M556. The biofilm elicited by
      insertion of bap into the chromosome of a biofilm-negative strain exhibited a
      similar dependence on the calcium concentration, indicating that the observed
      calcium inhibition was an inherent property of the Bap-mediated biofilms. Site
      directed mutagenesis of two of the putative EF-hand domains resulted in a mutant
      strain that was capable of forming a biofilm but whose biofilm was not inhibited
      by calcium. Our results indicate that Bap binds Ca2+ with low affinity and that
      Ca2+ binding renders the protein noncompetent for biofilm formation and for
      intercellular adhesion. The fact that calcium inhibition of Bap-mediated
      multicellular behavior takes place in vitro at concentrations similar to those
      found in milk serum supports the possibility that this inhibition is relevant to
      the pathogenesis and/or epidemiology of the bacteria in the mastitis process.

PMID- 15516561
TI  - Characteristics of zinc transport by two bacterial cation diffusion facilitators
      from Ralstonia metallidurans CH34 and Escherichia coli.
AB  - CzcD from Ralstonia metallidurans and ZitB from Escherichia coli are prototypes
      of bacterial members of the cation diffusion facilitator (CDF) protein family.
      Expression of the czcD gene in an E. coli mutant strain devoid of zitB and the
      gene for the zinc-transporting P-type ATPase zntA rendered this strain more zinc
      resistant and caused decreased accumulation of zinc. CzcD, purified as an amino
      terminal streptavidin-tagged protein, bound Zn2+, Co2+, Cu2+, and Ni2+ but not
      Mg2+, Mn2+, or Cd2+, as shown by metal affinity chromatography. Histidine
      residues were involved in the binding of 2 to 3 mol of Zn2+ per mol of CzcD. ZitB
      transported 65Zn2+ in the presence of NADH into everted membrane vesicles with an
      apparent Km of 1.4 microM and a Vmax of 0.57 nmol of Zn2+ min(-1) mg of protein(
      1). Conserved amino acyl residues that might be involved in binding and transport
      of zinc were mutated in CzcD and/or ZitB, and the influence on Zn2+ resistance
      was studied. Charged or polar amino acyl residues that were located within or
      adjacent to membrane-spanning regions of the proteins were essential for the full
      function of the proteins. Probably, these amino acyl residues constituted a
      pathway required for export of the heavy metal cations or for import of counter
      flowing protons.

PMID- 15516562
TI  - Evolutionary dynamics of insertion sequences in Helicobacter pylori.
AB  - Prokaryotic insertion sequence (IS) elements behave like parasites in terms of
      their ability to invade and proliferate in microbial gene pools and like
      symbionts when they coevolve with their bacterial hosts. Here we investigated the
      evolutionary history of IS605 and IS607 of Helicobacter pylori, a genetically
      diverse gastric pathogen. These elements contain unrelated transposase genes
      (orfA) and also a homolog of the Salmonella virulence gene gipA (orfB). A total
      of 488 East Asian, Indian, Peruvian, and Spanish isolates were screened, and 18
      and 14% of them harbored IS605 and IS607, respectively. IS605 nucleotide sequence
      analysis (n = 42) revealed geographic subdivisions similar to those of H. pylori;
      the geographic subdivision was blurred, however, due in part to homologous
      recombination, as indicated by split decomposition and homoplasy tests (homoplasy
      ratio, 0.56). In contrast, the IS607 populations (n = 44) showed strong
      geographic subdivisions with less homologous recombination (homoplasy ratio,
      0.2). Diversifying selection (ratio of nonsynonymous change to synonymous change,
      >>1) was evident in approximately 15% of the IS605 orfA codons analyzed but not
      in the IS607 orfA codons. Diversifying selection was also evident in
      approximately 2% of the IS605 orfB and approximately 10% of the IS607 orfB codons
      analyzed. We suggest that the evolution of these elements reflects selection for
      optimal transposition activity in the case of IS605 orfA and for interactions
      between the OrfB proteins and other cellular constituents that potentially
      contribute to bacterial fitness. Taken together, similarities in IS elements and
      H. pylori population genetic structures and evidence of adaptive evolution in IS
      elements suggest that there is coevolution between these elements and their
      bacterial hosts.

PMID- 15516563
TI  - Sequence organization and insertion specificity of the novel chimeric ISHp609
      transposable element of Helicobacter pylori.
AB  - Here we describe ISHp609 of Helicobacter pylori, a new member of the IS605 mobile
      element family that is novel and contains two genes whose functions are unknown,
      jhp960 and jhp961, in addition to homologs of two other H. pylori insertion
      sequence (IS) element genes, orfA, which encodes a putative serine recombinase
      transposase, and orfB, whose homologs in other species are also often annotated
      as genes that encode transposases. The complete four-gene element was found in 10
      to 40% of strains obtained from Africa, India, Europe, and the Americas but in
      only 1% of East Asian strains. Sequence comparison of 10 representative ISHp609
      elements revealed higher levels of DNA sequence matches (99%) than those seen in
      normal chromosomal genes (88 to 98%) or in other IS elements (95 to 97% for
      IS605, IS606, and IS607) from the same H. pylori populations. Sequence analysis
      suggested that ISHp609 can insert at many genomic sites with its left end
      preferentially next to TAT, with no target specificity for its right end, and
      without duplicating or deleting target sequences. A deleted form of ISHp609,
      containing just jhp960 and jhp961 and 37 bp of orfA, found in reference strain
      J99, was at the same chromosomal site in 15 to 40% of the strains from many
      geographic regions but again in only 1% of the East Asian strains. The abundance
      and sequence homogeneity of ISHp609 and of this nonmobile remnant suggested a
      recent bottleneck and then rapid spread in H. pylori populations, possibly
      selected by the contributions of the elements to bacterial fitness.

PMID- 15516564
TI  - Increased motility of Escherichia coli by insertion sequence element integration
      into the regulatory region of the flhD operon.
AB  - The flhD operon is the master operon of the flagellar regulon and a global
      regulator of metabolism. The genome sequence of the Escherichia coli K-12 strain
      MG1655 contained an IS1 insertion sequence element in the regulatory region of
      the flhD promoter. Another stock of MG1655 was obtained from the E. coli Genetic
      Stock Center. This stock contained isolates which were poorly motile and had no
      IS1 element upstream of the flhD promoter. From these isolates, motile
      subpopulations were identified after extended incubation in motility agar.
      Purified motile derivatives contained an IS5 element insertion upstream of the
      flhD promoter, and swarm rates were sevenfold higher than that of the original
      isolate. For a motile derivative, levels of flhD transcript had increased 2.7
      fold, leading to a 32-fold increase in fliA transcript and a 65-fold increase in
      flhB::luxCDABE expression from a promoter probe vector. A collection of commonly
      used lab strains was screened for IS element insertion and motility. Five strains
      (RP437, YK410, MC1000, W3110, and W2637) contained IS5 elements upstream of the
      flhD promoter at either of two locations. This correlated with high swarm rates.
      Four other strains (W1485, FB8, MM294, and RB791) did not contain IS elements in
      the flhD regulatory region and were poorly motile. Primer extension determined
      that the transcriptional start site of flhD was unaltered by the IS element
      insertions. We suggest that IS element insertion may activate transcription of
      the flhD operon by reducing transcriptional repression.

PMID- 15516565
TI  - Transfer of the symbiotic plasmid of Rhizobium etli CFN42 requires cointegration
      with p42a, which may be mediated by site-specific recombination.
AB  - Plasmid p42a from Rhizobium etli CFN42 is self-transmissible and indispensable
      for conjugative transfer of the symbiotic plasmid (pSym). Most pSym
      transconjugants also inherit p42a. pSym transconjugants that lack p42a always
      contain recombinant pSyms, which we designated RpSyms*. RpSyms* do not contain
      some pSym segments and instead have p42a sequences, including the replication and
      transfer regions. These novel recombinant plasmids are compatible with wild-type
      pSym, incompatible with p42a, and self-transmissible. The symbiotic features of
      derivatives simultaneously containing a wild-type pSym and an RpSym* were
      analyzed. Structural analysis of 10 RpSyms* showed that 7 shared one of the two
      pSym-p42a junctions. Sequencing of this common junction revealed a 53-bp region
      that was 90% identical in pSym and p42a, including a 5-bp central region flanked
      by 9- to 11-bp inverted repeats reminiscent of bacterial and phage attachment
      sites. A gene encoding an integrase-like protein (intA) was localized downstream
      of the attachment site on p42a. Mutation or the absence of intA abolished pSym
      transfer from a recA mutant donor. Complementation with the wild-type intA gene
      restored transfer of pSym. We propose that pSym-p42a cointegration is required
      for pSym transfer; cointegration may be achieved either through homologous
      recombination among large reiterated sequences or through IntA-mediated site
      specific recombination between the attachment sites. Cointegrates formed through
      the site-specific system but resolved through RecA-dependent recombination or
      vice versa generate RpSyms*. A site-specific recombination system for plasmid
      cointegration is a novel feature of these large plasmids and implies that there
      is unique regulation which affects the distribution of pSym in nature due to the
      role of the cointegrate in conjugative transfer.

PMID- 15516566
TI  - Staphylococcus aureus AgrA binding to the RNAIII-agr regulatory region.
AB  - The control of virulence gene expression in the human pathogen Staphylococcus
      aureus is under the partial control of the two-component quorum-sensing system
      encoded by genes of the agr locus. The product of the agrA gene has been shown by
      amino acid sequence similarity to be the putative response regulator; however,
      binding of AgrA to promoters under its control has not yet been demonstrated. In
      this study, we isolated and purified soluble AgrA by expression under osmotic
      shock conditions and ion-exchange chromatography. Purified AgrA showed high
      affinity binding to the RNAIII-agr intergenic region by electrophoretic mobility
      shift assays. Binding was localized by DNase I protection assays to a pair of
      direct repeats in the P2 and P3 promoter regions of the agr locus. We found that
      this binding was enhanced by the addition of the small phosphoryl donor, acetyl
      phosphate. The difference in binding affinity between these two promoters was
      found to result from a 2-bp difference between the downstream direct repeats of
      the P2 and P3 sites. Mutation of these base pairs in the P3 site to match those
      found in the P2 site increased the affinity of AgrA for the P3 site relative to
      that for the P2 site. These results are consistent with the function of AgrA as a
      response regulator with recognition sites in the promoter regions of RNAIII and
      the agr locus.

PMID- 15516567
TI  - Ligand-specific activation of Escherichia coli chemoreceptor transmethylation.
AB  - Adaptation in the chemosensory pathways of bacteria like Escherichia coli is
      mediated by the enzyme-catalyzed methylation (and demethylation) of glutamate
      residues in the signaling domains of methyl-accepting chemotaxis proteins (MCPs).
      MCPs can be methylated in trans, where the methyltransferase (CheR) molecule
      catalyzing methyl group transfer is tethered to the C terminus of a neighboring
      receptor. Here, it was shown that E. coli cells exhibited adaptation to
      attractant stimuli mediated through either engineered or naturally occurring MCPs
      that were unable to tether CheR as long as another MCP capable of tethering CheR
      was also present, e.g., either the full-length aspartate or serine receptor (Tar
      or Tsr). Methylation of isolated membrane samples in which engineered tethering
      and substrate receptors were coexpressed demonstrated that the truncated
      substrate receptors (trTsr) were efficiently methylated in the presence of
      tethering receptors (Tar with methylation sites blocked) relative to samples in
      which none of the MCPs had tethering sites. The effects of ligand binding on
      methylation were investigated, and an increase in rate was produced only with
      serine (the ligand specific for the substrate receptor trTsr); no significant
      change in rate was produced by aspartate (the ligand specific for the tethering
      receptor Tar). Although the overall efficiency of methylation was lower, receptor
      specific effects were also observed in trTar- and trTsr-containing samples, where
      neither Tar nor Tsr possessed the CheR binding site at the C terminus.
      Altogether, the results are consistent with a ligand-induced conformational
      change that is limited to the methylated receptor dimer and does not spread to
      adjacent receptor dimers.

PMID- 15516568
TI  - Decaprenyl diphosphate synthesis in Mycobacterium tuberculosis.
AB  - Z-prenyl diphosphate synthases catalyze the sequential condensation of
      isopentenyl diphosphate with allylic diphosphates to synthesize polyprenyl
      diphosphates. In mycobacteria, these are precursors of decaprenyl phosphate, a
      molecule which plays a central role in the biosynthesis of essential
      mycobacterial cell wall components, such as the mycolyl-arabinogalactan
      peptidoglycan complex and lipoarabinomannan. Recently, it was demonstrated that
      open reading frame Rv2361c of the Mycobacterium tuberculosis H37Rv genome encodes
      a unique prenyl diphosphate synthase (M. C. Schulbach, P. J. Brennan, and D. C.
      Crick, J. Biol. Chem. 275:22876-22881, 2000). We have now purified the enzyme to
      near homogeneity by using an Escherichia coli expression system and have shown
      that the product of this enzyme is decaprenyl diphosphate. Rv2361c has an
      absolute requirement for divalent cations and an optimal pH range of 7.5 to 8.5,
      and the activity is stimulated by both detergent and dithiothreitol. The enzyme
      catalyzes the addition of isopentenyl diphosphate to geranyl diphosphate, neryl
      diphosphate, omega,E,E-farnesyl diphosphate, omega,E,Z-farnesyl diphosphate, or
      omega,E,E,E-geranylgeranyl diphosphate, with Km values for the allylic substrates
      of 490, 29, 84, 290, and 40 microM, respectively. The Km value for isopentenyl
      diphosphate is 89 microM. The catalytic efficiency is greatest when omega,E,Z
      farnesyl diphosphate is used as the allylic acceptor, suggesting that this is the
      natural substrate in vivo, a conclusion that is supported by previous structural
      studies of decaprenyl phosphoryl mannose isolated from M. tuberculosis. This is
      the first report of a bacterial Z-prenyl diphosphate synthase that preferentially
      utilizes an allylic diphosphate primer having the alpha-isoprene unit in the Z
      configuration, indicating that Rv1086 (omega,E,Z-farnesyl diphosphate synthase)
      and Rv2361c act sequentially in the biosynthetic pathway that leads to the
      formation of decaprenyl phosphate in M. tuberculosis.

PMID- 15516569
TI  - Chlamydiaphage Chp2, a skeleton in the phiX174 closet: scaffolding protein and
      procapsid identification.
AB  - Chlamydiaphage Chp2 is a member of the family Microviridae, of which
      bacteriophage phiX174 is the type species. Although grouped in the same family,
      the relationship between the Microviridae coliphages and the Chp2-like viruses,
      which infect obligate intracellular parasitic bacteria, is quite distant, with
      major differences in structural protein content and scaffolding protein
      dependence. To investigate the morphogenesis of Chp2, large particles were
      isolated from infected Chlamydophila abortus by equilibrium and rate zonal
      sedimentation. A monoclonal antibody that recognizes only assembled viral coat
      proteins was used in these detection assays. Thus, the detected particles
      represent virions and/or postcapsid formation assembly intermediates. Two
      distinct particle types were detected, differing in both protein and DNA content.
      Filled particles lacked VP3, the putative internal scaffolding protein, whereas
      empty particles contained this protein. These results indicate that VP3 is a
      scaffolding protein and that the isolated VP3-containing particles most likely
      represent Chp2 procapsids.

PMID- 15516570
TI  - MucA-mediated coordination of type III secretion and alginate synthesis in
      Pseudomonas aeruginosa.
AB  - The type III secretion system (T3SS) of Pseudomonas aeruginosa is an important
      virulence factor. The T3SS of P. aeruginosa can be induced by a low calcium
      signal or upon direct contact with the host cells. The exact pathway of signal
      sensing and T3SS activation is not clear. By screening a transposon insertion
      mutant library of the PAK strain, mutation in the mucA gene was found to cause
      repression of T3SS expression under both type III-inducing and -noninducing
      conditions. Mutation in the mucA gene is known to cause alginate overproduction,
      resulting in a mucoid phenotype. Alginate production responds to various
      environmental stresses and plays a protective role for P. aeruginosa. Comparison
      of global gene expression of mucA mutant and wild-type PAK under T3SS-inducing
      conditions confirmed the down regulation of T3SS genes and up regulation of genes
      involved in alginate biosynthesis. Further analysis indicated that the repression
      of T3SS in the mucA mutant was AlgU and AlgR dependent, as double mutants
      mucA/algU and mucA/algR showed normal type III expression. An algR::Gm mutant
      showed a higher level of type III expression, while overexpression of the algR
      gene inhibited type III gene expression; thus, it seems that the AlgR-regulated
      product inhibits the expression of the T3SS genes. It is likely that P.
      aeruginosa has evolved tight regulatory networks to turn off the energy-expensive
      T3SS when striving for survival under environmental stresses.

PMID- 15516571
TI  - Analysis of the cytoplasmic domains of Salmonella FlhA and interactions with
      components of the flagellar export machinery.
AB  - Most flagellar proteins are exported via a type III export apparatus which, in
      part, consists of the membrane proteins FlhA, FlhB, FliO, FliP, FliQ, and FliR
      and is housed within the membrane-supramembrane ring formed by FliF subunits.
      Salmonella FlhA is a 692-residue integral membrane protein with eight predicted
      transmembrane spans. Its function is not understood, but it is necessary for
      flagellar export. We have created mutants in which potentially important
      sequences were deleted. FlhA lacking the amino-terminal sequence prior to the
      first transmembrane span failed to complement and was dominant negative,
      suggesting that the sequence is required for function. Similar effects were seen
      in a variant lacking a highly conserved domain (FHIPEP) within a putative
      cytoplasmic loop. Scanning deletion analysis of the cytoplasmic domain (FlhAc)
      demonstrated that substantially all of FlhAc is required for efficient function.
      Affinity blotting showed that FlhA interacts with several other export apparatus
      membrane proteins. The implications of these findings are discussed, and a model
      of FlhA within the export apparatus is presented.

PMID- 15516572
TI  - Pyruvate formate lyase and acetate kinase are essential for anaerobic growth of
      Escherichia coli on xylose.
AB  - During anaerobic growth of bacteria, organic intermediates of metabolism, such as
      pyruvate or its derivatives, serve as electron acceptors to maintain the overall
      redox balance. Under these conditions, the ATP needed for cell growth is derived
      from substrate-level phosphorylation. In Escherichia coli, conversion of glucose
      to pyruvate yields 2 net ATPs, while metabolism of a pentose, such as xylose, to
      pyruvate only yields 0.67 net ATP per xylose due to the need for one (each) ATP
      for xylose transport and xylulose phosphorylation. During fermentative growth, E.
      coli produces equimolar amounts of acetate and ethanol from two pyruvates, and
      these reactions generate one additional ATP from two pyruvates (one hexose
      equivalent) while still maintaining the overall redox balance. Conversion of
      xylose to acetate and ethanol increases the net ATP yield from 0.67 to 1.5 per
      xylose. An E. coli pfl mutant lacking pyruvate formate lyase cannot convert
      pyruvate to acetyl coenzyme A, the required precursor for acetate and ethanol
      production, and could not produce this additional ATP. E. coli pfl mutants failed
      to grow under anaerobic conditions in xylose minimal medium without any negative
      effect on their survival or aerobic growth. An ackA mutant, lacking the ability
      to generate ATP from acetyl phosphate, also failed to grow in xylose minimal
      medium under anaerobic conditions, confirming the need for the ATP produced by
      acetate kinase for anaerobic growth on xylose. Since arabinose transport by AraE,
      the low-affinity, high-capacity, arabinose/H+ symport, conserves the ATP expended
      in pentose transport by the ABC transporter, both pfl and ackA mutants grew
      anaerobically with arabinose. AraE-based xylose transport, achieved after
      constitutively expressing araE, also supported the growth of the pfl mutant in
      xylose minimal medium. These results suggest that a net ATP yield of 0.67 per
      pentose is only enough to provide for maintenance energy but not enough to
      support growth of E. coli in minimal medium. Thus, pyruvate formate lyase and
      acetate kinase are essential for anaerobic growth of E. coli on xylose due to
      energetic constraints.

PMID- 15516573
TI  - Two distinct genotypes of prtF2, encoding a fibronectin binding protein, and
      evolution of the gene family in Streptococcus pyogenes.
AB  - The group A Streptococcus (GAS) is an important pathogen that is responsible for
      a wide range of human diseases. Fibronectin binding proteins (FBPs) play an
      important role in promoting GAS adherence and invasion of host cells. The prtF2
      gene encodes an FBP and is present in approximately 60% of GAS strains. In the
      present study we examined 51 prtF2-positive GAS strains isolated from the
      Northern Territory of Australia, and here we describe two genotypes of prtF2
      which are mutually exclusive. The two genotypes have been identified previously
      as pfbp and fbaB. We show that these genotypes map to the same chromosomal
      location within the highly recombinatorial fibronectin-collagen-T antigen (FCT)
      locus, indicating that they arose from a common ancestor, and in this study these
      genotypes were designated the pfbp type and the fbaB type. Phylogenetic analysis
      of seven pfbp types, 14 fbaB types, and 11 prtF2-negative GAS strains by pulsed
      field gel electrophoresis (PFGE) produced 32 distinct PFGE patterns.
      Interpretation of evolution based on the PFGE dendrogram by parsimony suggested
      that the pfbp type had a recent origin compared to the fbaB type. A comparison of
      multiple DNA sequences of the pfbp and fbaB types revealed a mosaic pattern for
      the amino-terminal region of the pfbp types. The fbaB type is generally conserved
      at the amino terminus but varies in the number of fibronectin binding repeats in
      the carboxy terminus. Our data also suggest that there is a possible association
      of the pfbp genotype with sof (84.2%), while the fbaB genotype was found in a
      majority of the GAS strains negative for sof (90.6%), indicating that these two
      prtF2 subtypes may be under different selective pressures.

PMID- 15516574
TI  - Role of CysE in production of an extracellular signaling molecule in Providencia
      stuartii and Escherichia coli: loss of CysE enhances biofilm formation in
      Escherichia coli.
AB  - A mini-Tn5Cm insertion has been identified that significantly reduced the amount
      of an extracellular activating signal for a lacZ fusion (cma37::lacZ) in
      Providencia stuartii. The transposon insertion was located immediately upstream
      of an open reading frame encoding a putative CysE ortholog. The CysE enzyme,
      serine acetyltransferase, catalyzes the conversion of serine to O-acetyl-L-serine
      (OAS). This activating signal was also produced by Escherichia coli, and
      production was abolished in a strain containing a null allele of cysE. Products
      of the CysE enzyme (OAS, N-acetyl-L-serine [NAS], O-acetyl-L-threonine, and N
      acetyl-L-threonine) were individually tested for the ability to activate
      cma37::lacZ. Only OAS was capable of activating the cma37::lacZ fusion. The
      ability of OAS to activate the cma37::lacZ fusion was abolished by pretreatment
      at pH 8.5, which converts OAS to NAS. However, the activity of the native signal
      in conditioned medium was not decreased by treatment at pH 8.5. In contrast,
      conditioned medium prepared from cells grown at pH 8.5 exhibited a 4- to 10-fold
      higher activity, relative to pH 6.0. Additional genes regulated by the CysE
      dependent signal and OAS were identified in P. stuartii and E. coli. The response
      to the extracellular signal in E. coli was dependent on CysB, a positive
      activator that requires NAS as a coactivator. In E. coli, a cysE mutant formed
      biofilms at an accelerated rate compared to the wild type, suggesting a
      physiological role for this extracellular signal.

PMID- 15516575
TI  - Continuous control in bacterial regulatory circuits.
AB  - We show that for two well-characterized regulatory circuits in Escherichia coli,
      Tn10 tetracycline resistance and porin osmoregulation, the transcriptional
      outputs in individual cells are graded functions of the applied stimuli. These
      systems are therefore examples of naturally occurring regulatory circuits that
      exhibit continuous control of transcription. Surprisingly, however, we find that
      porin osmoregulation is open loop; i.e., the porin expression level does not feed
      back into the regulatory circuit. This mode of control is particularly
      interesting for an organism such as E. coli, which proliferates in diverse
      environments, and raises important questions regarding the biologically relevant
      inputs and outputs for this system.

PMID- 15516576
TI  - Lack of YggX results in chronic oxidative stress and uncovers subtle defects in
      Fe-S cluster metabolism in Salmonella enterica.
AB  - As components involved in Fe-S cluster metabolism are described, the challenge
      becomes defining the integrated process that occurs in vivo based on the
      individual functions characterized in vitro. Strains lacking yggX have been used
      here to mimic chronic oxidative stress and uncover subtle defects in Fe-S cluster
      metabolism. We describe the in vivo similarities and differences between isc
      mutants, which have a known function in cluster assembly, and mutants disrupted
      in four additional loci, gshA, apbC, apbE, and rseC. The latter mutants share
      similarities with isc mutants: (i) a sensitivity to oxidative stress, (ii) a
      thiamine auxotrophy in the absence of the YggX protein, and (iii) decreased
      activities of Fe-S proteins, including aconitase, succinate dehydrogenase, and
      MiaB. However, they differ from isc mutants by displaying a phenotypic dependence
      on metals and a distinct defect in the SoxRS response to superoxides. Results
      presented herein support the proposed role of YggX in iron trafficking and
      protection against oxidative stress, describe additional phenotypes of isc
      mutants, and suggest a working model in which the ApbC, ApbE, and RseC proteins
      and glutathione participate in Fe-S cluster repair.

PMID- 15516577
TI  - Evidence that a B12-adenosyl transferase is encoded within the ethanolamine
      operon of Salmonella enterica.
AB  - Adenosylcobalamin (Ado-B12) is both the cofactor and inducer of ethanolamine
      ammonia lyase (EA-lyase), a catabolic enzyme for ethanolamine. De novo synthesis
      of Ado-B12 by Salmonella enterica occurs only under anaerobic conditions.
      Therefore, aerobic growth on ethanolamine requires import of Ado-B12 or a
      precursor (CN-B12 or OH-B12) that can be adenosylated internally. Several known
      enzymes adenosylate corrinoids. The CobA enzyme transfers adenosine from ATP to a
      biosynthetic intermediate in de novo B12 synthesis and to imported CN-B12, OH
      B12, or Cbi (a B12 precursor). The PduO adenosyl transferase is encoded in an
      operon (pdu) for cobalamin-dependent propanediol degradation and is induced by
      propanediol. Evidence is presented here that a third transferase (EutT) is
      encoded within the operon for ethanolamine utilization (eut). Surprisingly, these
      three transferases share no apparent sequence similarity. CobA produces
      sufficient Ado-B12 to initiate eut operon induction and to serve as a cofactor
      for EA-lyase when B12 levels are high. Once the eut operon is induced, the EutT
      transferase supplies more Ado-B12 during the period of high demand. Another
      protein encoded in the operon (EutA) protects EA-lyase from inhibition by CN-B12
      but does so without adenosylation of this corrinoid.

PMID- 15516578
TI  - Molecular identification of the urea uptake system and transcriptional analysis
      of urea transporter- and urease-encoding genes in Corynebacterium glutamicum.
AB  - The molecular identification of the Corynebacterium glutamicum urea uptake system
      is described. This ABC-type transporter is encoded by the urtABCDE operon, which
      is transcribed in response to nitrogen limitation. Expression of the urt genes is
      regulated by the global nitrogen regulator AmtR, and an amtR deletion strain
      showed constitutive expression of the urtABCDE genes. The AmtR repressor protein
      also controls transcription of the urease-encoding ureABCEFGD genes in C.
      glutamicum. The ure gene cluster forms an operon which is mainly transcribed in
      response to nitrogen starvation. To confirm the increased synthesis of urease
      subunits under nitrogen limitation, proteome analyses of cytoplasmic protein
      extracts from cells grown under nitrogen surplus and nitrogen limitation were
      carried out, and five of the seven urease subunits were identified.

PMID- 15516579
TI  - The CorA Mg2+ transporter does not transport Fe2+.
AB  - corA encodes the constitutively expressed primary Mg2+ uptake system of most
      eubacteria and many archaea. Recently, a mutation in corA was reported to make
      Salmonella enterica serovar Typhimurium markedly resistant to Fe2+-mediated
      toxicity. Mechanistically, this was hypothesized to be from an ability of CorA to
      mediate the influx of Fe2+. Consequently, we directly examined Fe2+ transport and
      toxicity in wild-type versus corA cells. As determined by direct transport assay,
      CorA cannot transport Fe2+ and Fe2+ does not potently inhibit CorA transport of
      63Ni2+. Mg2+ can, relatively weakly, inhibit Fe2+ uptake, but inhibition is not
      dependent on the presence of a functional corA allele. Although excess Fe2+ was
      slightly toxic to S. enterica serovar Typhimurium, we were unable to elicit a
      significant differential sensitivity in a wild-type versus a corA strain. We
      conclude that CorA does not transport Fe2+ and that the relationship, if any,
      between iron toxicity and corA is indirect.

PMID- 15516580
TI  - Purification and characterization of the repressor of the shiga toxin-encoding
      bacteriophage 933W: DNA binding, gene regulation, and autocleavage.
AB  - The genes encoding Shiga toxin (stx), the major virulence factor of Shiga toxin
      encoding Escherichia coli (STEC) strains, are carried on lambdoid prophages
      resident in all known STEC strains. The stx genes are expressed only during lytic
      growth of these temperate bacteriophages. We cloned the gene encoding the
      repressor of the Shiga toxin-encoding bacteriophage 933W and examined the DNA
      binding and transcriptional regulatory activities of the overexpressed, purified
      protein. Typical of nearly all lambdoid phage repressors, 933W repressor binds to
      three sites in 933W right operator (OR). Also typical, when bound at OR, 933W
      repressor functions as an activator at the PRM promoter and a repressor at the PR
      promoter. In contrast to other lambdoid bacteriophages, 933W left operator (OL)
      contains only two repressor binding sites, but the OL-bound repressor still
      efficiently represses PL transcription. Lambdoid prophage induction requires
      inactivation of the repressor's DNA binding activity. In all phages examined thus
      far, this inactivation requires a RecA-stimulated repressor autoproteolysis
      event, with cleavage occurring precisely in an Ala-Gly dipeptide sequence that is
      found within a "linker " region that joins the two domains of these proteins.
      However, 933W repressor protein contains neither an Ala-Gly nor an alternative
      Cys-Gly dipeptide cleavage site anywhere in its linker sequence. We show here
      that the autocleavage occurs at a Leu-Gly dipeptide. Thus, the specificity of the
      repressor autocleavage site is more variable than thought previously.

PMID- 15516581
TI  - The operator and early promoter region of the Shiga toxin type 2-encoding
      bacteriophage 933W and control of toxin expression.
AB  - The genes encoding Shiga toxin (Stx), the major virulence factor of Shiga toxin
      producing Escherichia coli, are carried in the genomes of bacteriophages that
      belong to the lambdoid family of phages. Previous studies demonstrated that
      induction of prophages encoding stx significantly enhances the production and/or
      release of Stx from the bacterium. Therefore, factors that regulate the switch
      between lysogeny and lytic growth, e.g., repressor, operator sites, and
      associated phage promoters, play important roles in regulating the production
      and/or release of Stx. We report the results of genetic and biochemical studies
      characterizing these elements of the Stx-encoding bacteriophage 933W. Like
      lambda, 933W has three operator repeats in the right operator region (OR), but
      unlike lambda and all other studied lambdoid phages, which have three operator
      repeats in the left operator region (OL), 933W only has two operator repeats in
      OL. As was observed with lambda, the 933W OR and OL regions regulate
      transcription from the early PR and PL promoters, respectively. A lysogen
      carrying a 933W derivative encoding a noncleavable repressor fails to produce
      Stx, unlike a lysogen carrying a 933W derivative encoding a cleavable repressor.
      This finding provides direct evidence that measurable expression of the stx genes
      encoded by a 933W prophage requires induction of that prophage with the
      concomitant initiation of phage gene expression.

PMID- 15516582
TI  - A novel archaeal alanine dehydrogenase homologous to ornithine cyclodeaminase and
      mu-crystallin.
AB  - A novel alanine dehydrogenase (AlaDH) showing no significant amino acid sequence
      homology with previously known bacterial AlaDHs was purified to homogeneity from
      the soluble fraction of the hyperthermophilic archaeon Archaeoglobus fulgidus.
      AlaDH catalyzed the reversible, NAD+-dependent deamination of L-alanine to
      pyruvate and NH4+. NADP(H) did not serve as a coenzyme. The enzyme is a homodimer
      of 35 kDa per subunit. The Km values for L-alanine, NAD+, pyruvate, NADH, and
      NH4+ were estimated at 0.71, 0.60, 0.16, 0.02, and 17.3 mM, respectively. The A.
      fulgidus enzyme exhibited its highest activity at about 82 degrees C (203 U/mg
      for reductive amination of pyruvate) yet still retained 30% of its maximum
      activity at 25 degrees C. The thermostability of A. fulgidus AlaDH was increased
      by more than 10-fold by 1.5 M KCl to a half-life of 55 h at 90 degrees C. At 25
      degrees C in the presence of this salt solution, the enzyme was approximately
      100% stable for more than 3 months. Closely related A. fulgidus AlaDH homologues
      were found in other archaea. On the basis of its amino acid sequence, A. fulgidus
      AlaDH is a member of the ornithine cyclodeaminase-mu-crystallin family of
      enzymes. Similar to the mu-crystallins, A. fulgidus AlaDH did not exhibit any
      ornithine cyclodeaminase activity. The recombinant human mu-crystallin was
      assayed for AlaDH activity, but no activity was detected. The novel A. fulgidus
      gene encoding AlaDH, AF1665, is designated ala.

PMID- 15516583
TI  - GntP is the Escherichia coli Fructuronic acid transporter and belongs to the UxuR
      regulon.
AB  - Escherichia coli has four gluconate transporters, GntP, GntU, GntT, and IdnT,
      which are members of the major facilitator superfamily. The physiological
      function of GntP was previously unknown and is the subject of this study. GntP is
      not induced by gluconate, and despite being located adjacent to genes involved in
      glucuronate catabolism, gntP does not encode a glucuronate transporter. Here we
      identify gntP as the gene which encodes the fructuronate transporter. We show
      that gntP is induced by fructuronate and is a new member of the UxuR regulon:
      gntP is derepressed in an uxuR strain, UxuR binds in vitro specifically to an
      operator site that overlaps the gntP promoter, and UxuR binding is eliminated by
      fructuronate. Transcription of gntP requires activation by cyclic AMP (cAMP)-cAMP
      receptor protein. A gntP mutant cannot grow on fructuronate but grows normally on
      glucuronate and gluconate. Thus, the UxuR regulon is a module of sugar acid
      catabolism whose physiological role is for growth on fructuronate. Glucuronate,
      because it proceeds through a fructuronate intermediate, must induce the UxuR
      regulon and must also induce the ExuR regulon, which encodes the glucuronate
      transporter, ExuT, and the first step in its catabolism, UxaC. Thus, hexuronate
      catabolism in E. coli requires both the ExuR and UxuR regulons, while
      fructuronate catabolism requires only the UxuR regulon.

PMID- 15516584
TI  - 8-oxo-7,8-dihydroguanine is removed by a nucleotide excision repair-like
      mechanism in Porphyromonas gingivalis W83.
AB  - A consequence of oxidative stress is DNA damage. The survival of Porphyromonas
      gingivalis in the inflammatory microenvironment of the periodontal pocket
      requires an ability to overcome oxidative stress caused by reactive oxygen
      species (ROS). 8-oxo-7,8-dihydroguanine (8-oxoG) is typical of oxidative damage
      induced by ROS. There is no information on the presence of 8-oxoG in P.
      gingivalis under oxidative stress conditions or on a putative mechanism for its
      repair. High-pressure liquid chromatography with electrochemical detection
      analysis of chromosomal DNA revealed higher levels of 8-oxoG in P. gingivalis
      FLL92, a nonpigmented isogenic mutant, than in the wild-type strain. 8-oxoG
      repair activity was also increased in cell extracts from P. gingivalis FLL92
      compared to those from the parent strain. Enzymatic removal of 8-oxoG was
      catalyzed by a nucleotide excision repair (NER)-like mechanism rather than the
      base excision repair (BER) observed in Escherichia coli. In addition, in
      comparison with other anaerobic periodontal pathogens, the removal of 8-oxoG was
      unique to P. gingivalis. Taken together, the increased 8-oxoG levels in P.
      gingivalis FLL92 could further support a role for the hemin layer as a unique
      mechanism in oxidative stress resistance in this organism. In addition, this is
      the first observation of an NER-like mechanism as the major mechanism for removal
      of 8-oxoG in P. gingivalis.

PMID- 15516585
TI  - Effect of host species on recG phenotypes in Helicobacter pylori and Escherichia
      coli.
AB  - Recombination is a fundamental mechanism for the generation of genetic variation.
      Helicobacter pylori strains have different frequencies of intragenomic
      recombination, arising from deletions and duplications between DNA repeat
      sequences, as well as intergenomic recombination, facilitated by their natural
      competence. We identified a gene, hp1523, that influences recombination
      frequencies in this highly diverse bacterium and demonstrate its importance in
      maintaining genomic integrity by limiting recombination events. HP1523 shows
      homology to RecG, an ATP-dependent helicase that in Escherichia coli allows
      repair of damaged replication forks to proceed without recourse to potentially
      mutagenic recombination. Cross-species studies done show that hp1523 can
      complement E. coli recG mutants in trans to the same extent as E. coli recG can,
      indicating that hp1523 has recG function. The E. coli recG gene only partially
      complements the hp1523 mutation in H. pylori. Unlike other recG homologs, hp1523
      is not involved in DNA repair in H. pylori, although it has the ability to repair
      DNA when expressed in E. coli. Therefore, host context appears critical in
      defining the function of recG. The fact that in E. coli recG phenotypes are not
      constant in other species indicates the diverse roles for conserved recombination
      genes in prokaryotic evolution.

PMID- 15516586
TI  - The bcr1 DNA repeat element is specific to the Bacillus cereus group and exhibits
      mobile element characteristics.
AB  - Bacillus cereus strains ATCC 10987 and ATCC 14579 harbor an approximately 155-bp
      repeated element, bcr1, which is conserved in B. cereus, B. anthracis, B.
      thuringiensis, and B. mycoides but not in B. subtilis and B. licheniformis. In
      this study, we show by Southern blot hybridizations that bcr1 is present in all
      54 B. cereus group strains tested but absent in 11 Bacillus strains outside the
      group, suggesting that bcr1 may be specific and ubiquitous to the B. cereus
      group. By comparative analysis of the complete genome sequences of B. cereus ATCC
      10987, B. cereus ATCC 14579, and B. anthracis Ames, we show that bcr1 is
      exclusively present in the chromosome but absent from large plasmids carried by
      these strains and that the numbers of full-length bcr1 repeats for these strains
      are 79, 54, and 12, respectively. Numerous copies of partial bcr1 elements are
      also present in the three genomes (91, 128, and 53, respectively). Furthermore,
      the genomic localization of bcr1 is not conserved between strains with respect to
      chromosomal position or organization of gene neighbors, as only six full-length
      bcr1 loci are common to at least two of the three strains. However, the
      intergenic sequence surrounding a specific bcr1 repeat in one of the three
      strains is generally strongly conserved in the other two, even in loci where bcr1
      is found exclusively in one strain. This finding indicates that bcr1 either has
      evolved by differential deletion from a very high number of repeats in a common
      ancestor to the B. cereus group or is moving around the chromosome. The
      identification of bcr1 repeats interrupting genes in B. cereus ATCC 10987 and
      ATCC 14579 and the presence of a flanking TTTAT motif in each end show that bcr1
      exhibits features characteristic of a mobile element.

PMID- 15516587
TI  - Responses of the Rhodobacter sphaeroides transcriptome to blue light under
      semiaerobic conditions.
AB  - Exposure to blue light of the facultative phototrophic proteobacterium
      Rhodobacter sphaeroides grown semiaerobically results in repression of the puc
      and puf operons involved in photosystem formation. To reveal the genome-wide
      effects of blue light on gene expression and the underlying photosensory
      mechanisms, transcriptome profiles of R. sphaeroides during blue-light
      irradiation (for 5 to 135 min) were analyzed. Expression of most photosystem
      genes was repressed upon irradiation. Downregulation of photosystem development
      may be used to prevent photooxidative damage occurring when the photosystem,
      oxygen, and high-intensity light are present simultaneously. The photoreceptor of
      the BLUF-domain family, AppA, which belongs to the AppA-PpsR antirepressor
      repressor system, is essential for maintenance of repression upon prolonged
      irradiation (S. Braatsch et al., Mol. Microbiol. 45:827-836, 2002). Transcriptome
      data suggest that the onset of repression is also mediated by the AppA-PpsR
      system, albeit via an apparently different sensory mechanism. Expression of
      several genes, whose products may participate in photooxidative damage defense,
      including deoxypyrimidine photolyase, glutathione peroxidase, and quinol
      oxidoreductases, was increased. Among the genes upregulated were genes encoding
      two sigma factors: sigmaE and sigma38. The consensus promoter sequences for these
      sigma factors were predicted in the upstream sequences of numerous upregulated
      genes, suggesting that coordinated action of sigmaE and sigma38 is responsible
      for the upregulation. Based on the dynamics of upregulation, the anti-sigmaE
      factor ChrR or its putative upstream partner is proposed to be the primary
      sensor. The identified transcriptome responses provided a framework for
      deciphering blue-light-dependent signal transduction pathways in R. sphaeroides.

PMID- 15516588
TI  - Z-ring-independent interaction between a subdomain of FtsA and late septation
      proteins as revealed by a polar recruitment assay.
AB  - FtsA, a member of the ATPase superfamily that includes actin and bacterial actin
      homologs, is essential for cell division of Escherichia coli and is recruited to
      the Z ring. In turn, recruitment of later essential division proteins to the Z
      ring is dependent on FtsA. In a polar recruitment assay, we found that FtsA can
      recruit at least two late proteins, FtsI and FtsN, to the cell poles
      independently of Z rings. Moreover, a unique structural domain of FtsA, subdomain
      1c, which is divergent in the other ATPase superfamily members, is sufficient for
      this recruitment but not required for the ability of FtsA to localize to Z rings.
      Surprisingly, targeting the 1c subdomain to the Z ring by fusing it to FtsZ could
      partially suppress a thermosensitive ftsA mutation. These results suggest that
      subdomain 1c of FtsA is a completely independent functional domain with an
      important role in interacting with a septation protein subassembly.

PMID- 15516589
TI  - Transcription of the rod-shaped viruses SIRV1 and SIRV2 of the hyperthermophilic
      archaeon sulfolobus.
AB  - The double-stranded DNA genomes of the crenarchaeal rudiviruses SIRV1 (32 kb) and
      SIRV2 (35 kb) were previously sequenced. Here we present results of the analysis
      of gene expression of these viruses at different time points after infection of
      the host cell, Sulfolobus islandicus, and of the mapping of transcriptional start
      sites. Transcription of both genomes starts simultaneously at multiple sites
      spread over the total length of the genome and from both strands. The earliest
      time point when viral transcripts could be detected in cells was 30 min after
      infection. At this time point all the viral genes, except one, were transcribed.
      Many genes were clustered and appeared to be transcribed as polycistronic
      messengers. Although the coat protein-encoding gene was initially also
      transcribed as a polycistronic messenger, an abundant monocistronic transcript of
      this gene was detected 2 to 3 h after infection, just before assembly of viral
      particles. The expression of a single gene, adjacent to the coat protein gene,
      was upregulated at the late phase of infection, suggesting that it might be
      involved in specific processing and activation of the coat protein messenger.
      Start sites of 13 transcripts from the SIRV1 genome have been mapped by primer
      extension, and promoter sequences have been identified. Similar to host
      promoters, these viral promoters all contain potential binding sites for the
      archaeal transcription factors TATA binding protein and transcription factor B.
      In addition, most of them contain a virus-specific consensus element, suggesting
      the involvement of alternative transcription factors.

PMID- 15516590
TI  - Identification and functional verification of archaeal-type phosphoenolpyruvate
      carboxylase, a missing link in archaeal central carbohydrate metabolism.
AB  - Despite the fact that phosphoenolpyruvate carboxylase (PEPC) activity has been
      measured and in some cases even purified from some Archaea, the gene responsible
      for this activity has not been elucidated. Using sensitive sequence comparison
      methods, we detected a highly conserved, uncharacterized archaeal gene family
      that is distantly related to the catalytic core of the canonical PEPC. To verify
      the predicted function of this archaeal gene family, we cloned a representative
      from the hyperthermophilic acidophile Sulfolobus solfataricus and functionally
      produced the corresponding enzyme as a fusion with the Escherichia coli maltose
      binding protein. The purified fusion protein indeed displayed highly thermostable
      PEPC activity. The structural and biochemical properties of the characterized
      archaeal-type PEPC (atPEPC) from S. solfataricus are in good agreement with
      previously reported biochemical analyses of other archaeal PEPC enzymes. The
      newly identified atPEPC, with its distinct properties, constitutes yet another
      example of the versatility of the enzymes of the central carbon metabolic
      pathways in the archaeal domain.

PMID- 15516591
TI  - Differential regulation of the PanA and PanB proteasome-activating nucleotidase
      and 20S proteasomal proteins of the haloarchaeon Haloferax volcanii.
AB  - The halophilic archaeon Haloferax volcanii produces three different proteins
      (alpha1, alpha2, and beta) that assemble into at least two 20S proteasome
      isoforms. This work reports the cloning and sequencing of two H. volcanii
      proteasome-activating nucleotidase (PAN) genes (panA and panB). The deduced PAN
      proteins were 60% identical with Walker A and B motifs and a second region of
      homology typical of AAA ATPases. The most significant region of divergence was
      the N terminus predicted to adopt a coiled-coil conformation involved in
      substrate recognition. Of the five proteasomal proteins, the alpha1, beta, and
      PanA proteins were the most abundant. Differential regulation of all five genes
      was observed, with a four- to eightfold increase in mRNA levels as cells entered
      stationary phase. In parallel with this mRNA increase, the protein levels of PanB
      and alpha2 increased severalfold during the transition from exponential growth to
      stationary phase, suggesting that these protein levels are regulated at least in
      part by mechanisms that control transcript levels. In contrast, the beta and PanA
      protein levels remained relatively constant, while the alpha1 protein levels
      exhibited only a modest increase. This lack of correlation between the mRNA and
      protein levels for alpha1, beta, and PanA suggests posttranscriptional mechanisms
      are involved in regulating the levels of these major proteasomal proteins.
      Together these results support a model in which the cell regulates the ratio of
      the different 20S proteasome and PAN proteins to modulate the structure and
      ultimately the function of this central energy-dependent proteolytic system.

PMID- 15516592
TI  - Single-molecule approach to bacterial genomic comparisons via optical mapping.
AB  - Modern comparative genomics has been established, in part, by the sequencing and
      annotation of a broad range of microbial species. To gain further insights, new
      sequencing efforts are now dealing with the variety of strains or isolates that
      gives a species definition and range; however, this number vastly outstrips our
      ability to sequence them. Given the availability of a large number of microbial
      species, new whole genome approaches must be developed to fully leverage this
      information at the level of strain diversity that maximize discovery. Here, we
      describe how optical mapping, a single-molecule system, was used to identify and
      annotate chromosomal alterations between bacterial strains represented by several
      species. Since whole-genome optical maps are ordered restriction maps, sequenced
      strains of Shigella flexneri serotype 2a (2457T and 301), Yersinia pestis (CO 92
      and KIM), and Escherichia coli were aligned as maps to identify regions of
      homology and to further characterize them as possible insertions, deletions,
      inversions, or translocations. Importantly, an unsequenced Shigella flexneri
      strain (serotype Y strain AMC[328Y]) was optically mapped and aligned with two
      sequenced ones to reveal one novel locus implicated in serotype conversion and
      several other loci containing insertion sequence elements or phage-related gene
      insertions. Our results suggest that genomic rearrangements and chromosomal
      breakpoints are readily identified and annotated against a prototypic sequenced
      strain by using the tools of optical mapping.

PMID- 15516593
TI  - Functional characterization of a catabolic plasmid from polychlorinated- biphenyl
      degrading Rhodococcus sp. strain RHA1.
AB  - Rhodococcus sp. strain RHA1, a potent polychlorinated-biphenyl (PCB)-degrading
      strain, contains three linear plasmids ranging in size from 330 to 1,100 kb. As
      part of a genome sequencing project, we report here the complete sequence and
      characterization of the smallest and least-well-characterized of the RHA1
      plasmids, pRHL3. The plasmid is an actinomycete invertron, containing large
      terminal inverted repeats with a tightly associated protein and a predicted open
      reading frame (ORF) that is similar to that of a mycobacterial rep gene. The
      pRHL3 plasmid has 300 putative genes, almost 21% of which are predicted to have a
      catabolic function. Most of these are organized into three clusters. One of the
      catabolic clusters was predicted to include limonene degradation genes.
      Consistent with this prediction, RHA1 grew on limonene, carveol, or carvone as
      the sole carbon source. The plasmid carries three cytochrome P450-encoding (CYP)
      genes, a finding consistent with the high number of CYP genes found in other
      actinomycetes. Two of the CYP genes appear to belong to novel families; the third
      belongs to CYP family 116 but appears to belong to a novel class based on the
      predicted domain structure of its reductase. Analyses indicate that pRHL3 also
      contains four putative "genomic islands" (likely to have been acquired by
      horizontal transfer), insertion sequence elements, 19 transposase genes, and a
      duplication that spans two ORFs. One of the genomic islands appears to encode
      resistance to heavy metals. The plasmid does not appear to contain any
      housekeeping genes. However, each of the three catabolic clusters contains
      related genes that appear to be involved in glucose metabolism.

PMID- 15516594
TI  - Global transcriptome analysis of the heat shock response of Shewanella
      oneidensis.
AB  - Shewanella oneidensis is an important model organism for bioremediation studies
      because of its diverse respiratory capabilities. However, the genetic basis and
      regulatory mechanisms underlying the ability of S. oneidensis to survive and
      adapt to various environmentally relevant stresses is poorly understood. To
      define this organism's molecular response to elevated growth temperatures,
      temporal gene expression profiles were examined in cells subjected to heat stress
      by using whole-genome DNA microarrays for S. oneidensis. Approximately 15% (n =
      711) of the total predicted S. oneidensis genes (n = 4,648) represented on the
      microarray were significantly up- or downregulated (P < 0.05) over a 25-min
      period after shift to the heat shock temperature. As expected, the majority of
      the genes that showed homology to known chaperones and heat shock proteins in
      other organisms were highly induced. In addition, a number of predicted genes,
      including those encoding enzymes in glycolysis and the pentose cycle, serine
      proteases, transcriptional regulators (MerR, LysR, and TetR families), histidine
      kinases, and hypothetical proteins were induced. Genes encoding membrane proteins
      were differentially expressed, suggesting that cells possibly alter their
      membrane composition or structure in response to variations in growth
      temperature. A substantial number of the genes encoding ribosomal proteins
      displayed downregulated coexpression patterns in response to heat stress, as did
      genes encoding prophage and flagellar proteins. Finally, a putative regulatory
      site with high conservation to the Escherichia coli sigma32-binding consensus
      sequence was identified upstream of a number of heat-inducible genes.

PMID- 15516595
TI  - Use of an antisense RNA strategy to investigate the functional significance of Mn
      catalase in the extreme thermophile Thermus thermophilus.
AB  - The expression of an antisense RNA revealed that an Mn-catalase was required in
      Thermus thermophilus for aerobic but not for anaerobic growth. The antisense
      system is based on the constitutive expression of a "bicistronic" transcript
      consisting of the kanamycin resistance gene mRNA followed by the antisense RNA
      against the selected target.

PMID- 15516596
TI  - Long-term effect of mutagenic DNA repair on accumulation of mutations in
      Pseudomonas syringae B86-17.
AB  - Forty replicate lineages of Pseudomonas syringae B86-17 cells expressing the
      rulAB mutagenic DNA repair (MDR) determinant or the rulB::Km MDR-deficient mutant
      GWS242 were passaged through single-cell bottlenecks (60 cycles), with a UV
      radiation (UVR) exposure given to half of the lineages at the beginning of each
      cycle. After every 10th bottleneck cycle, single-colony isolates from all 80
      lineages were subjected to 39 phenotypic screens, with newly arising mutations
      detected in 60 and 0% of UVR-exposed or non-UVR-exposed B86-17 lineages,
      respectively, by the 60th cycle. Cellular fitness, measured as growth rate in a
      minimal medium, of UVR-exposed lineages of both B86-17 and GWS242 after 60 cycles
      was not significantly different from that of the ancestral strains. Although UVR
      exposure and MDR activity increased the occurrence of mutations in cells, a
      significant reduction in overall fitness was not observed.

PMID- 15516597
TI  - Mutation of a single lytic transglycosylase causes aberrant septation and
      inhibits cell separation of Neisseria gonorrhoeae.
AB  - The function of lytic peptidoglycan transglycosylases is poorly understood.
      Single lytic transglycosylase mutants of Escherichia coli have no growth
      phenotype. By contrast, mutation of Neisseria gonorrhoeae ltgC inhibited cell
      separation without affecting peptidoglycan monomer production. Thus, LtgC has a
      dedicated function in gonococcal cell division.

PMID- 15516598
TI  - Cuprous oxidase activity of CueO from Escherichia coli.
AB  - We have found CueO from Escherichia coli to have a robust cuprous oxidase
      activity, severalfold higher than any homologue. These data suggest that a
      functional role for CueO in protecting against copper toxicity in vivo includes
      the removal of Cu(I).

PMID- 15516599
TI  - Cold sensitivity of thermophilic and mesophilic RNA polymerases.
AB  - RNA polymerase from mesophilic Deinococcus radiodurans displays the same cold
      sensitivity of promoter opening as RNA polymerase from the closely related
      thermophilic Thermus aquaticus. This suggests that, contrary to the accepted
      view, cold sensitivity of promoter opening by thermophilic RNA polymerases may
      not be a consequence of their thermostability.

PMID- 15516600
TI  - In vivo production of active nickel superoxide dismutase from Prochlorococcus
      marinus MIT9313 is dependent on its cognate peptidase.
AB  - Metal-dependent superoxide dismutases (SODs) with a specific requirement for a
      manganese or iron ion for catalytic activity and copper- and zinc-dependent
      enzymes are essential for detoxification of superoxide anion radicals. Genome
      sequence analyses predict the existence of a nickel-dependent enzyme (NiSOD) as
      the unique SOD in oxygen-evolving marine cyanobacteria. NiSOD activity was
      observed in Escherichia coli when sodN and sodX (encoding a putative peptidase)
      from Prochlorococcus marinus MIT9313 were coexpressed.

PMID- 15516601
TI  - Intravenous contrast material administration at 16-detector row helical CT
      coronary angiography: test bolus versus bolus-tracking technique.
AB  - PURPOSE: To compare test bolus and bolus-tracking techniques for intravenous
      contrast material administration at 16-detector row computed tomographic (CT)
      coronary angiography. MATERIALS AND METHODS: This study had institutional review
      board approval, and patients gave informed consent. Thirty-eight patients (mean
      age, 60 years; three women) were randomized into two groups according to bolus
      timing technique: group 1 (20-mL test bolus with 100-mL main bolus) and group 2
      (bolus tracking with 100-mL main bolus). All patients underwent
      electrocardiography-gated 16-detector row CT coronary angiography with 12
      detectors (collimation, 0.75 mm; rotation time, 420 msec). In group 1, test bolus
      peak attenuation was used as a delay, while in group 2, a +100-HU threshold in
      ascending aorta triggered angiographic acquisition, with an additional 4-second
      delay for patient instruction. Attenuation was measured in the longitudinal
      direction throughout the examination in three main vessels: ascending aorta
      (region of interest [ROI] 1), descending aorta (ROI 2), and main pulmonary artery
      (ROI 3). Mean attenuation and slope of bolus geometry curve were calculated in
      each patient and ROI. Attenuation at origin of coronary arteries was measured.
      Student t test was used to compare results. RESULTS: Mean scan delay was 6
      seconds longer in group 2 (P < .05). Average attenuation values were 306.6 HU +/-
      44.0 (standard deviation) and 328.2 HU +/- 58.6 (P > .05) in ROI 1, 291.6 HU +/-
      45.1 and 326.4 HU +/- 62.6 (P > .05) in ROI 2, and 354.7 HU +/- 78.0 and 305.3 HU
      +/- 71.4 (P < .05) in ROI 3 for groups 1 and 2, respectively. Average slope
      values were 5.8 and -0.8 (P < .05) in ROI 1, 7.7 and 0.7 (P < .05) in ROI 2, and 
      1.0 and -13.3 (P < .05) in ROI 3 for groups 1 and 2, respectively. Average
      attenuation values in left main, left anterior descending, and left circumflex
      arteries were higher in group 2 (P < .05); there were no differences (P > .05)
      between groups in right coronary artery. CONCLUSION: Bolus-tracking yields more
      homogeneous enhancement than does the test bolus technique.

PMID- 15516602
TI  - Small hypoattenuating hepatic lesions at contrast-enhanced CT: prognostic
      importance in patients with breast cancer.
AB  - PURPOSE: To retrospectively determine the prognostic importance of small
      hypoattenuating hepatic lesions at contrast material-enhanced computed tomography
      (CT) in patients with breast cancer. MATERIALS AND METHODS: This retrospective
      study was approved by the committee on human research. Written informed consent
      was not required. The authors retrospectively identified 153 patients with breast
      cancer who underwent serial abdominal CT and who did not have definite liver
      metastases present at initial CT. The mean age was 56 years (age range, 27-93
      years). Two readers independently recorded the presence, size, and number of
      small (15 mm or less in diameter) hypoattenuating hepatic lesions at initial CT.
      Another reader independently recorded the presence or absence of definite hepatic
      metastases at final CT. The association between the presence, size, and number of
      small hypoattenuating hepatic lesions at initial CT and the subsequent
      development of metastases was analyzed by using Kaplan-Meier analysis. RESULTS:
      One or more small hypoattenuating hepatic lesions were seen at initial CT in 54
      of 153 patients (35%). After a median follow-up of 584 days (range, 16-1827
      days), definite hepatic metastases developed in 43 of 153 patients (28%),
      including 15 of 54 patients (28%) with hypoattenuating lesions at initial CT and
      28 of 99 patients (28%) without hypoattenuating lesions at initial CT. Findings
      from the Kaplan-Meier analysis showed no association between the presence (P =
      .56), size (P = .55), or number (P = .30) of small hypoattenuating hepatic
      lesions at initial CT and the subsequent development of hepatic metastases.
      CONCLUSION: In patients with breast cancer who do not have definite hepatic
      metastases at initial examination, there is no evidence that small
      hypoattenuating hepatic lesions seen at initial CT contribute to an increased
      risk of subsequently developing hepatic metastases.

PMID- 15516603
TI  - Infant sedation for MR imaging and CT: oral versus intravenous pentobarbital.
AB  - PURPOSE: To compare the effectiveness and safety of oral (PO) versus intravenous
      (IV) pentobarbital sedation for magnetic resonance (MR) imaging and computed
      tomography (CT) in infants younger than 12 months. MATERIALS AND METHODS: The
      institutional review board approved the review of medical records and determined
      informed consent to be unnecessary. All parents gave informed consent for patient
      sedation. Prior to MR imaging or CT, infants younger than 12 months were sedated
      with PO pentobarbital (4-8 mg per kilogram body weight) or IV pentobarbital (2-6
      mg/kg), depending on the presence of an IV catheter or need for IV contrast
      medium. A computer database used to record sedation data was reviewed for data
      from January 1997 to September 2003. PO and IV sedation groups were compared for
      mean age, weight, dose, time to sedation, time to discharge, and duration of
      sedation with a two-sample Student t test. Multivariate analysis of covariance
      was used to determine whether differences in sedation time, time to discharge,
      and duration of sedation between groups were independent of age, weight, sex,
      American Society of Anesthesiologists physical status classification, dose, and
      type of procedure. Sedation effectiveness (outcome) was determined as the
      percentage of sedation failures in each group. Safety was determined separately
      for other adverse events as a total and for respiratory adverse events. RESULTS:
      A total of 2164 infants received 2419 (1264 PO, 1155 IV) doses of pentobarbital
      for sedation. Weight and sex were comparable between groups. Time to sedation was
      significantly longer with PO than with IV pentobarbital (18 minutes +/- 11 vs 7
      minutes +/- 7; P < .01), but time to discharge was similar, at approximately 108
      minutes +/- 35. Total adverse events rate during sedation was not significantly
      different (0.8% [PO] vs 1.3% [IV]), but incidence of abnormal oxygen saturation
      (5% decrease from baseline, >1 minute duration) differed significantly (0.2% [PO]
      vs 0.9% [IV]; P = .02). Sedation effectiveness was comparable (failure rate, 0.5%
      [PO] vs 0.3% [IV]; P = .76). CONCLUSION: PO pentobarbital has comparable
      effectiveness and a lower rate of respiratory complications compared with IV
      pentobarbital in infants younger than 12 months; its use should be considered,
      regardless of presence of an IV catheter.

PMID- 15516604
TI  - Cartilage thickness in cadaveric ankles: measurement with double-contrast multi
      detector row CT arthrography versus MR imaging.
AB  - PURPOSE: To test the accuracy of double-contrast multi-detector row computed
      tomographic (CT) arthrography for measurement of cartilage thickness in cadaveric
      ankles and to compare this technique with three-dimensional (3D) fat-suppressed
      spoiled gradient-echo in the steady state (FS-SPGR) magnetic resonance (MR)
      imaging. MATERIALS AND METHODS: Five cadaveric ankles were used. In the ankle
      specimens, five to nine 1.5-mm-diameter holes were drilled across the joint
      traversing the tibial subchondral bone, tibial articular cartilage, talar dome
      cartilage, and talar subchondral bone. The ankle specimens were obtained and used
      according to institutional policies. Each ankle specimen was imaged first by
      using 3D FS-SPGR MR imaging with a 1.5-T magnet and then by using double-contrast
      arthrography followed by CT with a four-detector row scanner (ie, double-contrast
      multi-detector row CT arthrography). The section thickness used for CT scanning
      was 1.0 mm reconstructed in 0.5-mm intervals. The MR and CT images obtained in
      the five specimens were then downloaded to a workstation, where a measurement
      tool was used to measure the cartilage thickness at each hole. The physical
      measurement of cartilage thickness at each hole was used as the reference
      standard with which the MR imaging and CT measurements were compared. Linear
      regression and correlation analyses were performed by using a statistical
      computer program. RESULTS: Double-contrast arthrography followed by multi
      detector row CT, as compared with 3D FS-SPGR MR imaging, enabled more accurate
      measurement of the physical cartilage thickness in the ankle (P < .001).
      CONCLUSION: In this study of five cadaveric ankles, multi-detector row CT
      arthrography was more accurate than 3D FS-SPGR MR imaging for measurement of
      articular cartilage thickness in the ankle.

PMID- 15516605
TI  - Blunt abdominal trauma: performance of CT without oral contrast material.
AB  - PURPOSE: To retrospectively evaluate multi-detector row computed tomography (CT)
      without oral contrast material for depiction of bowel and mesenteric injuries
      that require surgical repair in patients with blunt abdominal trauma. MATERIALS
      AND METHODS: The investigational review board approved the study. Informed
      consent was waived. CT reports for October 2001 to September 2003 were reviewed
      and 1082 patients were identified who had undergone abdominopelvic CT with a
      multi-detector row scanner and without oral contrast material. Findings were
      divided into four categories: negative, solid organ injury with or without
      hemoperitoneum, free fluid only, and suspected bowel or mesenteric injury.
      Sensitivity, specificity, positive predictive value, and negative predictive
      value were calculated by comparing CT findings with laparotomy reports and
      hospital course. RESULTS: CT findings were no intraabdominal injury (n = 932),
      solid organ injury only (n = 102), free fluid only (n = 34), and suspected bowel
      or mesenteric injury (n = 14). CT findings in patients suspected of having bowel
      or mesenteric injury were pneumoperitoneum with other secondary findings (n = 4),
      mesenteric hematoma and bowel wall abnormality (n = 2), mesenteric hematoma only
      (n = 4), and bowel wall thickening only (n = 4). In 11 patients, bowel or
      mesenteric injury was proved surgically. Thus, the study included 1066 true
      negative, nine true-positive, two false-negative, and five false-positive
      results. Based on these data, sensitivity was 82% (95% confidence interval [CI]:
      52%, 95%), specificity was 99% (95% CI: 98%, 99%), positive predictive value was
      64% (95% CI: 39%, 83%), and negative predictive value was 99% (95% CI: 98%, 99%)
      for depiction of bowel and mesenteric injuries. CONCLUSION: Multi-detector row CT
      without oral contrast material is adequate for depiction of bowel and mesenteric
      injuries that require surgical repair. Results are comparable with previously
      reported data for single-detector row helical CT with oral contrast material.

PMID- 15516606
TI  - Defining intrahepatic biliary anatomy in living liver transplant donor candidates
      at mangafodipir trisodium-enhanced MR cholangiography versus conventional T2
      weighted MR cholangiography.
AB  - PURPOSE: To compare three-dimensional (3D) mangafodipir trisodium-enhanced T1
      weighted magnetic resonance (MR) cholangiography with conventional T2-weighted MR
      cholangiography for depiction and definition of intrahepatic biliary anatomy in
      liver transplant donor candidates. MATERIALS AND METHODS: One hundred eight
      healthy liver transplant donor candidates were examined with two MR
      cholangiographic methods. All candidates gave written informed consent, and the
      study was approved by the institutional review board. First, breath-hold
      transverse and coronal half-Fourier single-shot turbo spin-echo and breath-hold
      oblique coronal heavily T2-weighted turbo spin-echo sequences were performed.
      Second, mangafodipir trisodium-enhanced breath-hold fat-suppressed 3D gradient
      echo sequences were performed through the ducts (oblique coronal plane) and
      through the entire liver (transverse plane). Interpretation of biliary anatomy
      findings, particularly variants affecting right liver lobe biliary drainage, and
      degree of interpretation confidence at both 3D mangafodipir trisodium-enhanced MR
      cholangiography and T2-weighted MR cholangiography were recorded and compared by
      using the Wilcoxon signed rank test. Then, consensus interpretations of both MR
      image sets together were performed. Intraoperative cholangiography was the
      reference-standard examination for 51 subjects who underwent right lobe
      hepatectomy. The McNemar test was used to compare the accuracies of the
      individual MR techniques with that of the consensus interpretation of both image
      sets together and to compare each technique with intraoperative cholangiography.
      RESULTS: Biliary anatomy was visualized with mangafodipir trisodium enhancement
      in all patients. Mangafodipir trisodium-enhanced image findings agreed with
      findings seen at combined interpretations significantly more often than did T2
      weighted image findings (in 107 [99%] vs 88 [82%] of 108 donor candidates, P <
      .001). Confidence was significantly higher with the mangafodipir trisodium
      enhanced images than with the T2-weighted images (mean confidence score, 4.5 vs
      3.4; P < .001). In the 51 candidates who underwent intraoperative
      cholangiography, mangafodipir trisodium-enhanced imaging correctly depicted the
      biliary anatomy more often than did T2-weighted imaging (in 47 [92%] vs 43 [84%]
      donor candidates, P = .14), whereas the two MR imaging techniques combined
      correctly depicted the anatomy in 48 (94%) candidates. CONCLUSION: Mangafodipir
      trisodium-enhanced 3D MR cholangiography depicts intrahepatic biliary anatomy,
      especially right duct variants, more accurately than does conventional T2
      weighted MR cholangiography.

PMID- 15516607
TI  - Myocardial infarction: optimization of inversion times at delayed contrast
      enhanced MR imaging.
AB  - Seventeen patients underwent magnetic resonance (MR) imaging for myocardial
      viability with a protocol approved by the institutional review board and gave
      written informed consent. Breath-hold cine inversion-recovery segmented k-space
      true fast imaging with steady-state precession sequence, referred to as inversion
      time (TI) mapping, was performed to determine optimal TI for myocardial
      infarction inversion-recovery imaging. From TI mapping, optimal TI was 180-315
      msec 10-15 minutes after administration of 0.15 mmol/kg of gadolinium-based
      contrast material. At that optimal TI, relative signal intensity of infarcted
      myocardium compared with uninfarcted myocardium was maximal (mean +/- standard
      deviation, 297.8% +/- 86.5), whereas signal-to-noise ratio of uninfarcted
      myocardium was minimal (4.5 +/- 1.2). When applied to conventional myocardial
      infarction inversion-recovery imaging, optimal TI resulted in nulling of signal
      intensity of uninfarcted myocardium in all patients and in excellent conspicuity
      of infarcted myocardium in all nine patients with visible infarction.

PMID- 15516608
TI  - Practice patterns in percutaneous image-guided intraabdominal abscess drainage:
      survey of academic and private practice centers.
AB  - PURPOSE: To evaluate current practice patterns of percutaneous image-guided
      abdominal and pelvic abscess drainage in academic and private practice centers.
      MATERIALS AND METHODS: The institutional review board did not require approval
      for this study. In a survey conducted between November 2002 and February 2003,
      493 questionnaires were sent to 193 academic and 300 private practice radiology
      departments in the United States. All recipients were informed of the study
      purpose. The survey included questions about departmental demographics, patient
      selection criteria for percutaneous abscess drainage (eg, abscess diameter at
      imaging, laboratory parameters such as white blood cell count, and clinical
      indications such as fever), use of analgesia or conscious sedation, drainage
      method, and imaging technique. The statistical significance of differences
      between respondent subgroups was analyzed with a Pearson or Mantel-Haenszel
      chi(2) test. RESULTS: Academic centers returned 95 questionnaires (49%), and
      private practice centers, 72 (24%). Percutaneous abscess drainage is performed by
      a fellowship-trained radiologist at 92 (97%) of 95 academic centers and 41 (79%)
      of 52 private practice centers (P < .001). Among 95 academic respondents and 52
      private practice respondents, respectively, 56 (59%) and 33 (63%) do not perform
      drainage if an abscess has a diameter of less than 3 cm; 30 (32%) and nine (17%),
      if the white blood cell count is normal; and 16 (17%) and six (12%), if the
      patient is afebrile. Most (90 [95%] of 95 academic, 45 [87%] of 52 private
      practice) respondents use conscious sedation. A transabdominal approach and 8-12
      F catheters are most frequently used by both groups. Academic respondents more
      frequently use transvaginal and transrectal approaches (54 [57%] and 51 [54%] of
      95, vs 16 [31%] and 15 [29%] of 52 private practice respondents; P = .003) and 14
      F catheters (69 [73%] of 95 vs 18 [35%] of 52; P < .001). CONCLUSION:
      Percutaneous drainage is usually performed by fellowship-trained radiologists in
      abscesses of more than 3 cm in diameter, for appropriate clinical indications
      (multiple parameters above the established threshold), by using conscious
      sedation and 8-12-F catheters.

PMID- 15516609
TI  - Can MR imaging be used to characterize fetal musculoskeletal development?

PMID- 15516610
TI  - Overconfidence, overexposure, and overprotection.

PMID- 15516611
TI  - Imaging technology and practice assessments: diagnostic performance, clinical
      relevance, and generalizability in a changing environment.

PMID- 15516613
TI  - Case 76: May-Thurner syndrome.

PMID- 15516614
TI  - Low-flow vascular malformations: MR-guided percutaneous sclerotherapy in
      qualitative and quantitative assessment of therapy and outcome.
AB  - PURPOSE: To prospectively assess the therapeutic procedure and outcome of
      magnetic resonance (MR)-guided percutaneous sclerotherapy in patients with low
      flow vascular malformations. MATERIALS AND METHODS: Seventy-six percutaneous
      sclerotherapy treatments were performed by one radiologist with real-time MR
      guidance in 15 patients (six female patients; mean age, 54.4 years +/- 11.1; nine
      male patients; mean age, 32.9 years +/- 14.1) with vascular malformations in the
      head and neck (n = 64), spine (n = 5), and extremities (n = 7). Qualitative
      assessment was used to analyze (a) individual success of therapy, (b) occurrence
      of complications, (c) time required for minimally invasive MR-guided
      sclerotherapy in regression analysis, (d) ability of MR imaging to depict
      postinterventional perfusion changes within the vascular malformation with
      calculation of changes in contrast-to-noise ratios, and (e) detection of volume
      changes at follow-up examinations with volumetric analysis. RESULTS: Percutaneous
      sclerotherapy was performed successfully and without complications by filling
      targeted vascular malformations with sclerosing agent. Induced vascular sclerosis
      was used to successfully treat individual predominant symptoms, such as
      hemorrhage, pain, cosmetic disfigurement, and functional impairment. Quantitative
      analysis focusing on the actual interventional length of time presented an
      acceleration over the 5-year time period, matching a cubic function in regression
      curve fit and taking 31 minutes 50 seconds +/- 14 minutes. Induced vascular
      thrombosis was identified in all treated portions on postinterventional images by
      the statistically significant changes in contrast-to-noise ratio (P < .05)
      compared with preinterventional imaging. On follow-up images (ie, those obtained
      after 12 weeks +/- 6), shrinkage was observed in targeted portions (67.2% +/-
      18.9). CONCLUSION: MR imaging allows safe guidance and monitoring of minimally
      invasive sclerotherapy and permits verification of therapeutic success
      postinterventionally and during follow-up examinations.

PMID- 15516615
TI  - Neoadjuvant chemotherapy of locally advanced breast cancer: predicting response
      with in vivo (1)H MR spectroscopy--a pilot study at 4 T.
AB  - PURPOSE: To determine if changes in the concentration of choline-containing
      compounds (tCho) from before primary systemic therapy (PST) to within 24 hours
      after the first treatment enable prediction of clinical response in patients with
      locally advanced breast cancer. MATERIALS AND METHODS: Sixteen women with biopsy
      confirmed locally advanced breast cancer scheduled to undergo doxorubicin-based
      PST were recruited. Magnetic resonance (MR) imaging and spectroscopy were
      performed at 4 T prior to treatment, within 24 hours after the first dose, and
      after the fourth dose. Lesion size was assessed by using gadolinium-enhanced MR
      imaging. Lesion tCho concentration was quantified by using single-voxel hydrogen
      1 MR spectroscopy. Statistical analysis was performed by using the Pearson
      correlation coefficient and the Wilcoxon rank sum test. RESULTS: Fourteen of 16
      patients completed the protocol. In one patient, the level of tCho was not
      measurable because of unfavorable lesion morphology for MR spectroscopy voxel
      placement. Of the remaining 13 patients, four had inflammatory breast cancer, six
      had invasive ductal carcinoma, two had invasive lobular carcinoma, and one had
      mixed invasive ductal and lobular carcinoma. On the basis of the Response
      Evaluation Criteria in Solid Tumors, eight of 13 patients had an objective
      response and five had no response. The change in concentration of tCho from
      baseline to within 24 hours after the first dose of PST showed significant
      positive correlation with the change in lesion size (R = 0.79, P = .001). Change
      in tCho concentration within 24 hours after first dose was significantly
      different between patients with objective response and those with no response (P
      = .007). CONCLUSION: These results suggest that the change in tCho concentration
      between baseline and 24 hours after the first dose of PST can serve as an
      indicator for predicting clinical response to doxorubicin-based chemotherapy in
      locally advanced breast cancer.

PMID- 15516617
TI  - Integrated FDG PET/CT in patients with persistent ovarian cancer: correlation
      with histologic findings.
AB  - PURPOSE: To prospectively evaluate the accuracy of integrated positron emission
      tomography (PET) and computed tomography (CT) for depiction of persistent ovarian
      carcinoma after first-line treatment, with use of histologic findings as the
      reference standard. MATERIALS AND METHODS: Thirty-one women (mean age, 55.9
      years) with ovarian carcinoma treated with primary cytoreductive surgery and
      followed up with platinum regimen chemotherapy were included. All 31 patients
      were scheduled for surgical second-look. Before surgical second-look, all
      patients underwent fluorodeoxyglucose (FDG) PET/CT. At PET/CT, three main
      categories of persistent disease were considered for data analysis: lymph nodal
      lesion, peritoneal lesion, and pelvic lesion. In all patients, imaging findings
      were compared with results of histologic examination after surgical second-look
      to determine the diagnostic accuracy of PET/CT in the evaluation of disease
      status. The kappa statistic (Cohen kappa) was used for statistical analysis.
      RESULTS: Seventeen (55%) of 31 patients had persistent tumor at histologic
      analysis after surgical second-look, and fourteen (45%) had no histologically
      proved tumor. The total number of lesions that was positive for tumor cells at
      histologic analysis was 41 (lymph nodes, n = 16; peritoneal lesions, n = 21;
      pelvic lesions, n = 4); maximum diameter of these lesions was 0.3-3.2 cm (mean,
      1.7 cm). A correlation was found between PET/CT and histologic analysis (kappa =
      0.48). The overall lesion-based sensitivity, specificity, accuracy, positive
      predictive value, and negative predictive value of PET/CT were 78%, 75%, 77%, 89%
      and 57%, respectively. In the detection of a tumor, a size threshold could be set
      at 0.5 cm, as this was the largest diameter of a lesion missed at PET/CT.
      CONCLUSION: Integrated PET/CT depicts persistent ovarian carcinoma with a high
      positive predictive value.

PMID- 15516618
TI  - Blunt abdominal injury in the pregnant patient: detection with US.
AB  - PURPOSE: To determine the accuracy of ultrasonography (US) for the detection of
      blunt intraabdominal injury in pregnant patients and to compare differences
      between pregnant and nonpregnant patients of childbearing age. MATERIALS AND
      METHODS: A retrospective review of results of all consecutive emergency blunt
      trauma US examinations performed at a level I trauma center from January 1995 to
      June 2002 was conducted. Data on demographics, free fluid location, and patient
      outcome were collected. Injuries were determined on the basis of results of
      computed tomography and/or laparotomy. The Student t test was used to detect
      differences between continuous variables, and chi(2) analysis was used to
      evaluate differences between proportions. RESULTS: A total of 2319 US
      examinations for blunt trauma were performed in girls and women between the ages
      of 10 and 50 years. There were 328 pregnant patients, 23 of whom had
      intraabdominal injury. The mean age of the pregnant patients was 24.7 years +/-
      6.1 (standard deviation) (age range, 14-42 years). In pregnant patients, the
      sensitivity of US was 61% (14 of 23 patients), the specificity was 94.4% (288 of
      305 patients), and the accuracy was 92.1% (302 of 328 patients). Pregnant
      patients were significantly more likely to have sustained injuries from assault
      (odds ratio: 2.6, P < .001). The most common pattern of free fluid accumulation
      detected at US in pregnant patients was that of fluid in the left and right upper
      quadrants and pelvis (n = 4, 29%); the second most common pattern was one of
      isolated pelvic fluid (n = 3, 21%). CONCLUSION: For detection of intraabdominal
      injury, US was less sensitive in pregnant patients than in nonpregnant patients
      but was highly specific in both subgroups. The sensitivity of US was highest in
      pregnant patients during the first trimester.

PMID- 15516619
TI  - Amplatzer atrial septal defect occluder for pediatric patients: radiographic
      appearance.
AB  - PURPOSE: To describe the chest radiographic appearance of the Amplatzer septal
      occluder (ASO) (AGA Medical Corporation, Golden Valley, Minn) for atrial septal
      defects (ASDs) in pediatric patients. MATERIALS AND METHODS: Two radiologists
      independently reviewed frontal and lateral chest radiographs obtained in young
      patients 24 hours after transcatheter ASD closure with the ASO. The appearance
      (flat disks or dots) and location of the ASO were recorded. The location was
      related to that of a thoracic vertebral body on frontal and lateral chest
      radiographs and to a line drawn between the anterior margin of the right hilum
      and the posterior margin of the inferior vena cava (hilar-caval line) on lateral
      radiographs; this line corresponded to the expected position of the interatrial
      septum. The relationship between ASO appearance and patient age was assessed with
      logistic regression and cumulative probability plots. RESULTS: Sixty-eight
      pediatric patients (age range, 1 month to 18 years; mean age, 4.2 years; 24 boys
      and 44 girls) were included. On frontal radiographs, the ASO center projected
      between T7 and T9, either to the right of or over the spinous processes of the
      vertebral body. On lateral radiographs, the ASO projected over (n = 66) or
      anterior to (n = 2) the hilar-caval line. On frontal radiographs, it appeared as
      one or two flat disks (n = 61) or as two metallic dots (n = 7). On lateral
      radiographs, it appeared as two flat disks (n = 54) or as two metallic dots (n =
      14). The relationship between increasing patient age and the metallic dot
      appearance on frontal and lateral radiographs and on the combination of frontal
      and lateral radiographs was highly significant in each case (P < .001, likelihood
      ratio chi(2) test), with r(2) values of 0.35, 0.20, and 0.28, respectively. ASDs
      were successfully occluded with the ASO in all patients except one, in whom
      trivial shunting was seen at 12-month follow-up. CONCLUSION: The ASO in pediatric
      patients has a characteristic radiographic appearance when properly positioned.

PMID- 15516620
TI  - The double posterior cruciate ligament sign.

PMID- 15516621
TI  - Routine chest radiography in a primary care setting.
AB  - PURPOSE: To determine the frequency, diagnostic yield, outcomes, cost, and rate
      of false-positive results of routine chest radiography performed in asymptomatic
      patients in the primary care setting. MATERIALS AND METHODS: Radiography reports
      on all patients who underwent routine or screening posteroanterior and lateral
      chest radiography at a university-affiliated primary care clinic in 2001 were
      reviewed. Radiographic results were coded as normal or minor findings or as major
      abnormalities, such as pulmonary nodules, requiring further diagnostic
      evaluation. Outcomes of patients with major abnormalities were established by
      using chart reviews or reviewing additional radiographs. Costs were estimated by
      using 2002 Medicare reimbursement rates. The main measures assessed were
      frequency, costs, and rate of false-positive results of routine chest
      radiography. RESULTS: Of 3812 radiographs obtained at the primary care clinic,
      1282 (34%) were ordered for routine or screening purposes by the referring
      physician. Nine hundred twenty-two radiographs were obtained in male patients and
      360 were obtained in female patients; their mean and median age was 49 years (age
      range, 4-87 years). Fifteen chest radiographs showed major abnormalities. No
      patient younger than 40 years had a major abnormality. Fourteen of the 15
      findings of major abnormalities proved to be false-positive. No disease requiring
      treatment was diagnosed as a result of radiographic findings. The total cost for
      follow-up radiography and computed tomography was US dollar 46,609.49.
      CONCLUSION: Routine chest radiography has low diagnostic yield in asymptomatic
      primary care patients.

PMID- 15516622
TI  - Spatially resolved imaging of myocardial function with strain-encoded MR:
      comparison with delayed contrast-enhanced MR imaging after myocardial infarction.
AB  - Strain-encoded magnetic resonance (MR) imaging was prospectively evaluated for
      direct imaging of systolic myocardial strain and compared with cross-registered
      delayed contrast material-enhanced MR imaging in five healthy volunteers and nine
      patients with infarction. Local contractile performance was decreased in
      infarcted myocardium versus that in remote and adjacent myocardium (P < .01) and
      in adjacent versus remote myocardium (P < .05). The extent of dysfunctional
      myocardium, as assessed with strain-encoded MR imaging, was greater than that of
      hyperenhancement, as assessed with delayed contrast-enhanced MR imaging (P <
      .05). Strain values obtained with strain-encoded MR imaging were strongly
      correlated with those obtained with three-dimensional tagged MR imaging (r =
      0.75, P < .001). Strain-encoded MR imaging provides spatially resolved (1.5 x 2.5
      mm) imaging and measurement of myocardial strain in humans without the need for
      postprocessing, which may improve routine comprehensive evaluation of myocardial
      viability.

PMID- 15516623
TI  - Supratentorial cerebrospinal fluid production rate in healthy adults:
      quantification with two-dimensional cine phase-contrast MR imaging with high
      temporal and spatial resolution.
AB  - A method for objectively determining supratentorial cerebrospinal fluid (CSF)
      production rate is described. The method employs cine phase-contrast magnetic
      resonance imaging with high temporal and spatial resolution at the level of the
      aqueduct of Sylvius. Automatic encircling of the aqueduct was accomplished by
      using a pulsatility-based segmentation approach. Results in 23 healthy adults (18
      men, five women; age range, 21-39 years) yielded an average CSF production rate
      of 305 microL/min +/- 145 (standard deviation); this rate is in good agreement
      with literature-reported values obtained with invasive ventriculolumbar perfusion
      measurements. Average operator imprecision was 23.1% if automatic segmentation
      was not used. The proposed method is potentially an effective means for measuring
      supratentorial CSF production rate in humans.

PMID- 15516624
TI  - Computer-aided detection of breast cancer.

PMID- 15516625
TI  - Multiple magnet ingestion alert.

PMID- 15516626
TI  - MR angiography with venous compression.

PMID- 15516627
TI  - Potential for misinterpretation of combined T1- and T2-weighted contrast-enhanced
      MR imaging of cartilage.

PMID- 15516628
TI  - Dust reduction in darkrooms.

PMID- 15516629
TI  - Detection of Cyclospora cayetanensis in animal fecal isolates from Nepal using an
      FTA filter-base polymerase chain reaction method.
AB  - Cyclospora cayetanensis is an emerging protozoan parasite capable of causing a
      protracted diarrheal illness in both immunocompromised and immunocompetent
      individuals. Ingestion of fresh produce and water sources contaminated with
      mature sporulated oocysts results in acquisition of cyclosporiasis. Currently, no
      animal model exists for the study of this pathogenic parasite and the only
      confirmed reservoir host for C. cayetanensis in nature is humans. Previously,
      Cyclospora-like oocysts had been detected by microscopy in several animals
      including non-human primates. However, their phylogenetic relationship to C.
      cayetanensis remained uncertain due to the limited availability of molecular
      techniques to differentiate and speciate these isolates. In the present study, we
      examined a series of fecal isolates obtained from dogs, chickens, and monkeys
      collected between May and September 2002 from several geographic regions of
      Nepal. All samples were examined by microscopy and a polymerase chain reaction
      (PCR) for the presence of C. cayetanensis. Both microscopic and conventional
      PCR/restriction fragment length polymorphism (RFLP) analysis demonstrated the
      presence of Cyclospora sp. in the fecal samples of two dogs, one chicken, and one
      monkey. Application of a species-specific multiplex PCR assay confirmed the
      presence of both Eimeria sp. and C. cayetanensis in the positive chicken sample
      and only C. cayetanensis in the dog and monkey samples. However, in the absence
      of tissue analysis, the assignment of these animals as a natural reservoir host
      for C. cayetanensis remains to be determined.

PMID- 15516630
TI  - Travel histories as risk factors in the analysis of urban malaria in Colombia.
AB  - Self-reported travel histories were used in a case-control study to determine
      whether movement of local residents to neighboring endemic areas was a risk
      factor for malaria in the town of Quibdo, Colombia. Multivariate analyses showed
      that among residents of Quibdo, traveling to an endemic area 8-14 days before
      disease onset was the strongest risk factor for both Plasmodium falciparum
      (adjusted odds ratio [OR] = 28.96, 95% confidence interval [CI] = 13.9-60.32) and
      P. vivax (adjusted OR = 14.24, 95% CI = 5.27-38.46) malaria. For P. falciparum,
      individuals who did not travel outside Quibdo during the 8-14 days before disease
      onset, but who reported traveling 1-7, 15-21, or 22-30 days before disease onset
      also had an increased risk of malaria. Conversely, use of protection against
      mosquitoes was negatively associated with P. falciparum. These results highlight
      the need for malaria control measures that target mobile populations. A
      definition of imported malaria that allows distinction of imported from
      autochthonous cases in Quibdo town is proposed.

PMID- 15516631
TI  - Assessing water-related risk factors for Buruli ulcer: a case-control study in
      Ghana.
AB  - To assess water-related risk factors of Buruli ulcer, a case-control study of 102
      patients (51 cases and 51 controls) was undertaken by matching age group, sex,
      and bacille Calmette-Guerin (BCG) vaccination history in Ghana. The factors used
      here for matching have previously been implicated as factors of Buruli ulcer, an
      emerging infectious disease. This is the first study to delineate a set of
      previously suspected, water-related risk factors, in a case-control study
      matching for age group, sex, and BCG vaccination status. The results of both
      bivariate and multivariate analyses presented a significantly high odds ratio
      (OR) only for swimming in rivers on a habitual basis (OR = 18.00, P < 0.01) among
      the major water-related risk factors. Use of water from rivers and ponds for
      drinking, cooking, bathing, and washing purposes were not significant risk
      factors. Our data suggest that swimming, or activities on riverbanks associated
      with it, is a risk factor.

PMID- 15516632
TI  - Effect of blocking the CXCL9/10-CXCR3 chemokine system in the outcome of
      endothelial-target rickettsial infections.
AB  - Rickettsiae cause systemic infections such as Rocky Mountain spotted fever and
      boutonneuse fever. The main cellular target of these obligately intracellular
      bacteria is the endothelium. T lymphocytes are the most important effectors of
      immunity, and the CXCR3 ligands CXCL9 and CXCL10 may play an important role in
      the T cell-mediated clearance of rickettsiae from the infected vasculature as
      suggested by recent expression studies. Here we showed that antibody-mediated
      neutralization of CXCL9 and CXCL10, and CXCR3 gene knockout, had no effect on
      survival or bacterial loads of mice infected with rickettsiae. We also
      demonstrated that rickettsiae triggered the endothelial expression of
      intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 in vivo.
      These findings suggested that antigenic presentation by endothelial cells
      together with an endothelial inflammatory phenotype induced by the rickettsial
      infection may be sufficient to arrest T cells and trigger their anti-rickettsial
      effector mechanisms without the need for chemokines.

PMID- 15516633
TI  - Short report: fluorescent Leishmania: application to anti-leishmanial drug
      testing.
AB  - Classic techniques for detecting the susceptibility of Leishmania to different
      drugs are time-consuming, laborious, and require the use of macrophages. The use
      of flow cytometry for monitoring Leishmania susceptibility to drugs is beginning
      to be implemented. Using green fluorescent protein (GFP), we have improved and
      simplified the screening procedure. We introduced a GFP marker into field strains
      of Leishmania causing kala-azar (visceral leishmaniasis) and explored the
      suitability of transgenic L. donovani promastigotes that constitutively express
      GFP in their cytoplasm as target cells for in vitro screening of anti-leishmanial
      drugs.

PMID- 15516634
TI  - Seroepidemiologic study of Leishmania infantum infection in Castilla-Leon, Spain.
AB  - Leishmaniasis has increased in importance in recent years because infection with
      human immunodeficiency virus (HIV) has emerged as a risk factor for this disease.
      However, the actual prevalence of leishmaniasis in the general population of
      Spain is unknown. We present a study of the seroprevalence of infection with
      Leishmania infantum in the general population of Castilla-Leon, Spain. A random
      sample of individuals presenting to health care clinics (4,825 sera) and of HIV
      infected patients in the autonomous community of Castilla-Leon was collected in
      1996. The sero-prevalence of antibodies to L. infantum was determined by an
      indirect enzyme immunoassay and found to be 4.9% in the general population. There
      was a significant increase in seroprevalence with age (P = 0.001), from 3.96% in
      those 14-20 years old to 7.2% in those > 70 years old. There were no significant
      differences between women and men (5.0% versus 4.9%; P = 0.9534). Seroprevalence
      was significantly higher in people from rural areas than in those from cities
      (6.0% versus 3.4%; P = 0.001). Patients infected with HIV had a seroprevalence
      for L. infantum of 64.0%. No differences were observed between women and men, and
      prevalence did not increase with age.

PMID- 15516635
TI  - Protection of C3HeB/FeJ mice against Leishmania amazonensis challenge after
      previous Leishmania major infection.
AB  - The Th1 response elicited in mice infected with Leishmania major has been used as
      a model to characterize cellular immune defects associated with L. amazonensis
      infection. However, it is not known if the immune response associated with the
      infection by virulent L. major parasites can promote resistance to a subsequent
      L. amazonensis infection. Our data demonstrate that C3HeB/FeJ mice infected
      subcutaneously with virulent L. major are resistant to an L. amazonensis
      challenge. The healing phenotype is characterized by a Th1 response as measured
      by increased production of interferon-gamma and low levels of interleukin-4 in
      the draining lymph node. Together, this indicates that the Th1 response
      associated with L. major infection can promote resistance to L. amazonensis
      infection and that it can be used as a tool to study the immune defects
      associated with L. amazonensis infection.

PMID- 15516636
TI  - Cryptosporidiosis among Bangladeshi children with diarrhea: a prospective,
      matched, case-control study of clinical features, epidemiology and systemic
      antibody responses.
AB  - We conducted a prospective case-control study to investigate the epidemiology,
      clinical features, and systemic antibody responses of cryptosporidiosis in
      Bangladeshi children. Forty-six children presenting to the International Center
      for Diarrheal Disease Research, Bangladesh in Dhaka, Bangladesh with diarrhea and
      Cryptosporidium spp. oocysts in the stool were enrolled as cases. Forty-six age
      matched children with diarrhea, but without cryptosporidial infection, were
      enrolled as controls. Thirty cases and 23 controls returned for follow-up three
      weeks after discharge. Infection with Cryptosporidium spp. occurred most commonly
      in those less than two years of age, was accompanied by watery diarrhea and
      vomiting, and was more likely to be associated with persistent diarrhea. Other
      than duration of diarrhea, there were no significant differences in clinical or
      epidemiologic features between cases and controls. Cryptosporidium-specific serum
      IgM levels were significantly higher in cases compared with controls at
      presentation. In addition, there was a significant increase in serum
      Cryptosporidium-specific serum IgG levels over the three-week follow-up period in
      cases compared with controls. Within the case group, there was no difference
      between children with acute and persistent diarrhea in the change in IgG levels
      over the follow-up period. However, there was a significant difference between
      children with acute and persistent diarrhea in changes in both IgA and IgM
      levels, with persistent diarrhea being associated with a decrease in levels of
      both antibodies.

PMID- 15516637
TI  - Delayed effectiveness of home-based interventions in reducing childhood diarrhea,
      Karachi, Pakistan.
AB  - We introduced home drinking water disinfection and handwashing with soap in
      Karachi squatter settlements to evaluate their effect on diarrhea. In April 2000,
      150 households received soap, 76 received dilute bleach and a water storage
      vessel, and 76 were enrolled as controls. In 2000, among households wealthy
      enough to own a refrigerator, children in households that received bleach and a
      vessel had a 73% lower incidence of diarrhea than controls; those that received
      soap had a 56% lower incidence. There was no reduction in diarrhea in
      intervention households without a refrigerator. In 2001, households that received
      bleach and a vessel had a 71% lower incidence of diarrhea and children in
      households that received soap had a 35% lower incidence than controls. In 2001,
      the interventions were equally effective in households that had a refrigerator
      and those that did not. Both of these home-based interventions were ultimately
      effective in preventing diarrhea, but only households of slightly higher
      socioeconomic status changed their behavior quickly enough to benefit during the
      first summer.

PMID- 15516638
TI  - A randomized comparison of two anemia treatment regimens in Tanzanian children.
AB  - We used a prospective, open-label randomized trial to evaluate two treatment
      regimens in Tanzanian children two months to four years of age presenting to a
      hospital with a packed cell volume (PCV) < 25%. Treatment was either standard (14
      days of ferrous sulfate and an antimalarial) or extended (three months of ferrous
      sulfate and three antimalarial treatments). The prevalence of anemia was measured
      two weeks after completion of treatment and six months after recruitment. Two
      weeks after completing treatment, the prevalence of PCV < 33% was 58% in the
      standard treatment arm and 44% in the extended treatment group (P = 0.04), and
      the mean PCV was significantly higher in the extended treatment arm (32.1%, SD =
      4.5% versus 30.8%, SD = 4.9%; P = 0.031). However, there was no difference in the
      prevalence of PCV < 25% in the first survey, and the benefits of extended therapy
      were only apparent six months after recruitment in children compliant with the
      extended treatment (odds ratio of PCV < 25% = 0.16, P = 0.06). Compliance was
      satisfactory in only 39% (82 of 209) of the children in the first week of
      treatment. Extending the duration of therapy and improving compliance may have
      health benefits for anemic children in malaria-endemic settings.

PMID- 15516639
TI  - The effects of short-term iron supplementation on iron status in infants in
      malaria-endemic areas.
AB  - Iron deficiency and Plasmodium falciparum malaria are the two main causes of
      anemia in young children in region endemic for this disease. The impact on iron
      status of prophylactic oral iron supplementation (2 mg/kg/day from two to six
      months of age) and the duration of this effect were assessed in a group of 832
      Tanzanian infants exposed to P. falciparum malaria. Iron parameters and red blood
      cell indices were assessed at 2, 5, 8, and 12 months of age. Infants who received
      iron supplements had a significantly lower prevalence of iron deficiency (P <
      0.01 at 5 months and P < 0.001 at 8 and 12 months). Red blood cell indices (mean
      corpuscular volume, mean cell hemoglobin, and mean cell hemoglobin concentration)
      were increased in children receiving iron supplementation and they did not differ
      between those protected and unprotected against malaria. The prevalence of
      ferropenia was similar in children protected against malaria and in those who
      were not protected and did not receive iron supplements (34.7% versus 37.3% at 12
      months of age). We concluded that iron supplementation between the ages of 2-6
      months improves iron status at least up to 12 months of age. Malaria infection
      does not contribute to iron deficiency.

PMID- 15516640
TI  - Short report: the use of a polymerase chain reaction to detect Echinococcus
      granulosus (G1 strain) eggs in soil samples.
AB  - Cystic echinococcosis is a re-emerging disease in central Asia. A total of 120
      soil samples taken from 30 gardens of rural homesteads in southern Kazakhstan
      were analyzed for the presence of taeniid eggs using a concentration technique.
      Of these, 21 (17.5%) were shown to be contaminated with taeniid eggs. These
      isolated taeniid eggs were further analyzed using a polymerase chain reaction
      specific for the G1 (sheep) strain of the tapeworm Echinococcus granulosus, and
      five samples were shown to be positive. This study demonstrates the widespread
      contamination of the environment with E. granulosus eggs in an Echinococcus
      endemic area and thus the potential for indirect transmission of E. granulosus to
      humans from such sources.

PMID- 15516641
TI  - Prevalence and predictors of Helicobacter pylori infection in children and adults
      from the Penan ethnic minority of Malaysian Borneo.
AB  - To determine the prevalence of Helicobacter pylori antigen carriage in stool in
      the Penan ethnic minority in Malaysian Borneo, we studied 295 Penans 0.6-89.0
      years of age from 1) the remote Limbang Division, 2) Mulu regional center, and 3)
      Belaga village. Overall, 37.7% of the subjects tested positive. Peak prevalence
      was reached by 10 years of age. There were no differences in age, sex, body mass
      index, and socioeconomic/domestic variables between antigen-positive and antigen
      negative subjects. In a logistic regression analysis, subjects from Limbang were
      least likely to be antigen-positive (odds ratio [OR] = 0.23, 95% confidence
      interval [CI] = 0.12-0.44 versus other sites, P < 0.001). Availability of a
      flushing toilet was protective against H. pylori carriage (OR = 0.51, 95% CI =
      0.27-0.95, P = 0.031). Infection with H. pylori among the Penan was less than
      reported in other low socioeconomic groups. The lowest prevalence in the most
      remote setting suggests that the infection has been a recent arrival in
      previously isolated communities.

PMID- 15516642
TI  - Physiographic and entomologic risk factors of malaria in Assam, India.
AB  - Fever surveys were conducted in several districts of the Indian state of Assam to
      ascertain the prevalence of malaria in relation to vector abundance, entomologic
      inoculation rates (EIRs), and geographic location of human settlements. Anopheles
      minimus were incriminated, but their relative abundance and biting rates varied
      among districts, and no significant correlation was observed between these two
      indicators (r = 0.43, P = 0.34). Plasmodium falciparum was the predominant
      parasite species except in two districts where P. vivax was the majority
      parasite. The EIRs per person/night were 0.46-0.71 in P. falciparum-predominant
      areas and 0.12 in the district where P. vivax predominated. The correlation of
      percentage of fever cases positive for malaria infection in each district with
      the corresponding EIR was not significant (r = 0.6, P = 0.21). Malaria cases were
      detected in all months of the year but peaked during May-June, which corresponded
      to the months of heavy rainfall. These were also the months with highest
      incidence of infection with P. falciparum. Malaria cases were observed in all age
      groups of both sexes, and there was clustering of cases in villages near the
      vector-breeding habitat (perennial seepage streams), and foothill villages.
      However, malaria incidences were consistently lower in villages within 5 km of
      the nearest health care facility, which were in town areas. The data presented
      are indicative of low-to-moderate levels of malaria transmission by An. minimus,
      and would be of value for developing future intervention strategies.

PMID- 15516643
TI  - Epidemiology of malaria transmission and development of natural immunity in a
      malaria-endemic village, San Dulakudar, in Orissa state, India.
AB  - We describe the epidemiology of malaria in San Dulakudar, a village in Sundargarh
      District in the state of Orissa in eastern India. Malaria transmission is
      perennial with Plasmodium falciparum, accounting for greater than 80% of malaria
      cases. Transmission intensity varies with season with high transmission after the
      monsoon rains in autumn and winter, low transmission in summer, and intermediate
      transmission in spring. The anthropophagic mosquito Anopheles fluviatilis was
      identified as the main vector for malaria transmission. Based on observations of
      spleen rates and supported by data on malaria parasite prevalence and malaria
      incidence, San Dulakudar can be classified as a hyperendemic area for P.
      falciparum malaria. Parasite prevalence and malaria incidence rates decrease with
      age, suggesting that residents of San Dulakudar develop immunity to malaria. The
      study demonstrates the presence of regions in the Indian subcontinent such as
      Sundargarh District where P. falciparum is the primary cause of malaria and where
      malaria transmission rates are comparable to those found in many parts of Africa.

PMID- 15516644
TI  - Community-wide reduction in prevalence and intensity of intestinal helminths as a
      collateral benefit of lymphatic filariasis elimination programs.
AB  - Annual mass treatment with antifilarial drugs is the cornerstone of the global
      program to eliminate lymphatic filariasis (LF). Although the primary goal of the
      program is to interrupt transmission of LF, additional public health benefits
      also are expected because of the known anthelminthic properties of these drugs.
      Since rapid re-infection with intestinal helminths occurs following treatment,
      annual de-worming may not be sufficient to produce a lasting reduction in the
      prevalence and intensity of these infections. We conducted stool examinations in
      four sentinel communities before and approximately nine months after each of two
      rounds of mass drug administration (MDA) with diethylcarbamazine and albendazole
      in the context of an LF elimination program in Leogane, Haiti. At baseline,
      overall Ascaris, Trichuris, and hookworm infection prevalences were 20.9%, 34.0%,
      and 11.2%, respectively (n = 2,716 stools). Nine months after the second MDA,
      Ascaris, Trichuris and hookworm prevalences had decreased significantly, to
      14.1%, 14.6%, and 2.0%, respectively (n = 814 stools). Infection intensity
      decreased significantly for all three parasites as well. These results
      demonstrate that substantial reductions in intestinal helminth infections are
      associated with mass treatment of filariasis in Haiti and are consistent with the
      conclusion that high levels of coverage for the LF program can decrease
      transmission of geohelminths.

PMID- 15516645
TI  - Duplex Doppler sonographic assessment of the effects of diethylcarbamazine and
      albendazole therapy on adult filarial worms and adjacent host tissues in
      Bancroftian filariasis.
AB  - We used duplex Doppler sonography to assess effects of diethylcarbamazine and
      albendazole therapy (DEC/ALB) on adult Wuchereria bancrofti in vivo. The study
      was performed in clinically normal Egyptian adults with blood microfilaria counts
      > 80/mL. Motile adult worms were observed before treatment in dilated scrotal
      lymphatic vessels in 28 of 36 men (78%) and over the proximal extremities in 5 of
      22 women (23%). Most worm nests were inactivated in the months following
      treatment (90% at 12 months). Circulating filarial antigen levels (a marker for
      living adult worms) also fell dramatically following treatment. Some men had
      intrascrotal calcifications and/or non-palpable hydroceles detectable by
      ultrasound before they were treated. New hydroceles and intrascrotal
      calcifications appeared after treatment in many cases. However, most of these
      were transient and of no clinical significance. Prevelance rates for hydrocele
      and intrascrotal calcifications 24 months after treatment were essentially the
      same as those prior to treatment. These results show that DEC/ALB is highly
      active against adult W. bancrofti. They also suggest that host responses to dying
      adult worms are important in the pathogenesis of filarial hydroceles.

PMID- 15516646
TI  - Comparison of dengue-1 virus envelope glycoprotein gene sequences from French
      Polynesia.
AB  - Dengue (DEN) is the leading arboviral infection of humans, with 100 million cases
      annually in the tropical areas of the world. The recent severe DEN-1 epidemic in
      French Polynesia in 2001, with an incidence rate of 16% and more than 45% of the
      cases with dengue hemorrhagic fever/dengue shock syndrome among 1,400
      hospitalized children and eight fatalities, led us to study this new circulating
      strain. The entire envelope (E) gene of two French Polynesian DEN-1 virus
      isolates from the two epidemics of 1988-1989 (FP89) and 2001 (FP01) were
      sequenced and compared with 29 published DEN-1 virus E gene sequences.
      Phylogenetic relationships showed that the FP89 strain belonged to genotype V and
      the FP01 strain to genotype IV based on studies on the same region of DEN-1 virus
      genome (1,485 nucleotides). The recent dengue epidemic in French Polynesia in
      2001 was probably due to the introduction of a new DEN-1 virus from Southeast
      Asia, since the minimum nucleotide divergence was 3.3% with A88, the Indonesian
      strain isolated in 1988 in Jakarta.

PMID- 15516647
TI  - Introduction of the American/Asian genotype of dengue 2 virus into the Yucatan
      State of Mexico.
AB  - A dengue (DEN) outbreak occurred in the Yucatan State of Mexico in 2002. Three
      isolates were obtained from patients presenting with DEN-like symptoms, and
      examined by partial nucleotide sequencing and phylogenetic analysis. The isolates
      were identified as DEN-2 viruses of the American-Asian genotype; this is the
      first report of this genotype in the Yucatan State. The DEN-2 viruses of the
      American-Asian genotype have been associated with more severe disease outcomes.
      Thus, its introduction into the Yucatan State presents a serious problem to
      public health authorities. During this outbreak, DEN virus infection was
      confirmed in 18% (282 of 1,560) of the patients who presented with DEN-like
      symptoms. Of these, 87 (31%) patients met the World Health Organization criteria
      for dengue hemorrhagic fever, including two patients who died. The majority (77%)
      of the patients experienced secondary infections in this epidemic.

PMID- 15516648
TI  - Genetic and phenotypic variation of West Nile virus in New York, 2000-2003.
AB  - West Nile virus (WNV) strains circulating during the first five years of WNV
      transmission in New York were collected, partial nucleotide sequences were
      determined, and in vitro and in vivo phenotypic analyses of selected strains were
      undertaken to determine whether observed increases in the intensity of enzootic
      and epidemic transmission in New York State during 2002 and 2003 were associated
      with viral genetic changes. Functionally diverse regions of the WNV genome were
      also compared to determine whether some regions may be more or less variable than
      others. The complete envelope coding regions of 67 strains and fragments of the
      nonstructural protein 5 (NS5) and 3' noncoding regions of 39 strains collected
      during 2002 and 2003 were examined. West Nile virus in New York remains
      relatively genetically homogeneous. Viral genetic diversity was greater in 2002
      and 2003 at both the nucleotide and amino acid levels than in previous years due
      to the emergence of a new WNV genotype in 2002. This genotype persisted and
      became dominant in 2003. Envelope and NS5 coding regions were approximately two
      fold more likely than the 3' untranslated region to contain nucleotide
      substitutions, and the envelope region was approximately three-fold more likely
      to contain amino acid substitutions than the NS5 region. Variation was noted in
      in vivo mosquito transmission assays, but not in in vitro growth studies. Strains
      belonging to the epizootiologically dominant clade were transmitted after
      approximately two fewer days of extrinsic incubation, providing a possible
      mechanism for the dominance of this clade. The observed increase in the intensity
      of WNV transmission beginning in 2002 was associated with an increase in viral
      genetic diversity that was the result of the emergence of an additional
      phylogenetic clade. This genotype seems to possess an advantage over previously
      recognized WNV strains in mosquito transmission phenotype.

PMID- 15516649
TI  - Mixed domestic infestation by Rhodnius prolixus Stal, 1859 and Panstrongylus
      geniculatus Latreille, 1811, vector incrimination, and seroprevalence for
      Trypanosoma cruzi among inhabitants in El Guamito, Lara State, Venezuela.
AB  - Mixed infestation of nymphs and adults of Rhodnius prolixus Stal, 1859 and
      Panstrongylus geniculatus Latreille, 1811 was detected in 3 (15%) of 20 dwellings
      in El Guamito, an endemic focus of Chagas disease in Lara State, Venezuela. In
      one of the houses, both species were positive for Trypanosoma cruzi: 14.3% (R.
      prolixus) and 20% (P. geniculatus ). The overall infection rate in 143 of 352 R.
      prolixus was 16.1%. Parasites isolated from R. prolixus were identified as T.
      cruzi I by random amplified polymorphic DNA analysis. Dot-enzyme-linked
      immunosorbent assays of 36 R. prolixus showed that 58.3% of the R. prolixus had
      fed on humans. The gut contents of one fifth-instar nymph of P. geniculatus that
      was positive for T. cruzi also reacted with anti-human serum. A questionnaire was
      used to gather data on the demographic and socioeconomic characteristics of the
      population. An indirect immunofluorescent test, an indirect hemaglutination test,
      and an ELISA were used to detect the presence of antibodies against T. cruzi in
      84 of 86 inhabitants and in 15.5% of people more than 20 years old. The relative
      risk (RR) of infection was greater in men than in women (RR = 1.61, 95%
      confidence interval = 0.54-4.80). Of the people more than 15 years old, 36.6% had
      no formal education. All respondents recognized triatomine bugs, but they did not
      relate them to Chagas disease transmission. A total of 85.7% of the houses were
      "ranchos" suitable for the colonization of triatomine bugs. The possible
      domiciliation of P. geniculatus and the implications of competition with R.
      prolixus for resources are discussed. Since there is no clear separation of food
      sources, abiotic factors such as microclimatic variation within houses may be
      critical to predict the outcome of the process of competition and potential
      domestication of this generally sylvatic species.

PMID- 15516650
TI  - Population dynamics of Aedes aegypti from a dengue hyperendemic urban setting in
      Colombia.
AB  - This study evaluated if the Aedes aegypti population in the city of Cali,
      Colombia was composed of genetically distinct local populations with different
      levels of insecticide resistance and dengue vector competence. Insecticide
      resistance was assayed biochemically and was associated with varying levels of
      mixed-function oxidases and non-specific esterases. The genes encoding those
      enzymes were under selective pressure from insecticides used to suppress Ae.
      aegypti populations. Vector competence showed heterogeneity among the vector
      populations ranging from 19% to 60%. Population genetic analysis of random
      amplified polymorphic DNA-polymerase chain reaction products, expressed as
      genetic distance, Wright's F(st), and migration rate (Nm), demonstrated moderate
      genetic differentiation among Ae. aegypti from four sites (F(st) = 0.085). The
      results from all characteristics evaluated in the study demonstrated spatial and
      temporal variation between Ae. aegypti populations. At any specific time, the
      local populations of Ae. aegypti were genetically differentiated and unique with
      respect to insecticide resistance and vector competence. Both characteristics
      changed independently.

PMID- 15516651
TI  - Molecular differentiation of colonized human malaria vectors by 28S ribosomal DNA
      polymorphisms.
AB  - Anopheles gambiae s.s. Giles, An. stephensi Liston, An. freeborni Aitken, and An.
      quadrimaculatus Say are cultured and studied in molecular genetic and transgenic
      laboratories with increasing frequency. With limited research space, these
      mosquitoes are often maintained in the same insectary. Under these conditions,
      cross-contamination of colonies can occur and have devastating consequences to
      affected research programs. We have developed a polymerase chain reaction-based
      assay targeting the 28S large subunit ribosomal RNA gene to easily differentiate
      between these four taxa and An. funestus Giles, which occurs in sympatry with An.
      gambiae. The resulting assay identifies individual mosquito preparations as well
      as all taxa within a mixed or pooled DNA template preparation.

PMID- 15516652
TI  - Bionomics and systematics of the oriental Anopheles sundaicus complex in relation
      to malaria transmission and vector control.
AB  - The taxonomic history, distribution, bionomics, systematics, and vector control
      strategies for the Anopheles sundaicus complex are reviewed in relation to
      malaria epidemiology. The lack of data on the bionomics, insecticide resistance,
      and vector capacity, as well as the general lack of surveillance and monitoring
      of potential vector populations, make the development of targeted control
      measures problematic. It will be necessary to elucidate, characterize and
      identify all members of the complex to determine their distributions, disease
      relationships, ecologic relationships, and resistance to insecticides. This
      knowledge is essential for epidemiologic studies, the design and implementation
      of appropriate vector control measures, and the development of strategies for
      monitoring and assessing the potential risk of malaria outbreaks due to members
      of the complex.

PMID- 15516653
TI  - Abstracts of the 53rd Annual Meeting of the American Society of Tropical Medicine
      and Hygiene: Fontainebleau Hilton, Miami Beach, Florida U.S.A., November 7-11,
      2004.

PMID- 15516658
TI  - Goals of asthma treatment: how high should we go?

PMID- 15516659
TI  - Respiratory monitoring: revisiting classical physiological principles with new
      tools.

PMID- 15516660
TI  - Tobacco smoke: old foe more important for asthma than commonly appreciated?

PMID- 15516661
TI  - The womb and lung function later in life.

PMID- 15516662
TI  - Oesophageal pH monitoring is of limited value in the diagnosis of "reflux-cough".
AB  - Reflux-cough is a diagnosis based on demonstrating both gastro-oesophageal reflux
      and a positive response to anti-reflux therapy. The authors sought to determine
      early and long-term response to therapy in patients with a "positive" 24 h
      oesophageal pH study, and identify any features which might predict response.
      Patients with chronic cough were recruited from July 1998 to July 2002. Those
      with a positive pH study were given dietary advice and an 8-week trial of
      omeprazole (20 mg b.i.d.). Response was judged after 8 weeks (clinical follow
      up), and at long-term follow-up (telephone questionnaire). A total of 146
      patients underwent pH monitoring with 82 (56.2%) "positive" studies. Follow-up
      data was available in 60 patients, with 49 receiving anti-reflux therapy, of
      which 20 (40.8%) reported a positive treatment response. At long-term follow-up
      (median 30 months), there was a significantly lower response (14 out of 49,
      28.5%), with no significant difference in either acid exposure times
      (distal/proximal) or symptom correlation between responders and nonresponders at
      early or long-term follow-up. In conclusion, despite "positive" pH studies, over
      half of the patients (55.1%) failed to respond to therapy. No features on pH
      monitoring accurately predicted response. Short-term response did not predict
      long-term response. The precise role for pH monitoring in the assessment of
      chronic cough remains to be defined.

PMID- 15516663
TI  - Medical thoracoscopy: hormone receptor content in pleural metastases due to
      breast cancer.
AB  - Pleural metastases are common in the course of breast cancer, but, to date, the
      role of oestrogen receptor (OR) and progesterone receptor (PgR) content in
      metastatic tissue has been poorly evaluated. A series of 50 consecutive patients
      with a history of breast cancer (median age 64 yrs, range 40-86 yrs), which
      presented with pleural effusion and therefore underwent medical thoracoscopy, was
      analysed. Metastatic pleural involvement was histologically confirmed in all
      patients. The hormone receptor status of the pleural metastases was investigated
      using the immunohistochemical method in 49 and the biochemical method in 31
      cases. The immunohistochemical test was performed using monoclonal antibodies.
      Biochemical analysis was performed on specimens quick-frozen in liquid nitrogen.
      OR and PgR were measured with the dextran-coated charcoal assay and Scatchard
      analysis. Immunohistochemical analysis yielded 29 OR-positive and 25 PgR-positive
      cases and biochemical analysis yielded 16 OR-positive and four PgR-positive
      cases, sometimes discrepant to hormone status of the primary breast cancer. Using
      a semiquantitative immunoreactive score, there was a significant association
      between receptor positivity and survival, but only for PgR positivity.
      Immunohistochemical and biochemical detection of hormone receptors (oestrogen and
      progesterone) in pleural metastases of breast cancer is feasible based on medical
      thoracoscopy as the method of choice, by which sufficient specimens may be
      obtained. The receptor status may enable a decision on antihormonal treatment.
      Whether a positive receptor status in pleural metastatic tissue is associated
      with a better prognosis remains to be confirmed.

PMID- 15516664
TI  - Effect of in utero growth retardation on lung function at follow-up of
      prematurely born infants.
AB  - The aim of the study was to determine if prematurely born children who had
      suffered intra-uterine growth retardation (IUGR) had more severe lung function
      abnormalities than those born an appropriate weight for gestational age (AGA).
      Analysis of the lung function results of 119 infants (median (range) gestational
      age of 30 (23-35) weeks) was undertaken. In total, 31 of the infants had suffered
      IUGR and were born small for gestational age (SGA). Functional residual capacity
      and airways resistance (Raw) were measured at a median post-natal age of 10 (6
      24) months. Specific airway conductance (sGaw) was calculated from thoracic gas
      volume and Raw. The SGA children were born at a greater gestational age and had a
      lower body weight at testing than the AGA children. Raw and sGaw differed between
      the SGA and AGA children. Regression analysis demonstrated that lung volumes were
      significantly related to body weight at testing, Raw was related to IUGR,
      maternal smoking and bronchopulmonary dysplasia, and sGaw to maternal smoking. In
      conclusion, these results suggest that prematurely born infants who have suffered
      intra-uterine growth retardation may be at increased risk of impaired lung
      function at follow-up.

PMID- 15516665
TI  - Smoking and asthma in adults.
AB  - Studies on the effect of smoking on adulthood asthma have provided contradictory
      results. The current authors conducted a population-based incident case-control
      study to assess the effects of current and past smoking on the development of
      asthma in adults. During a 2.5 yr study period, all new asthma cases clinically
      diagnosed (n=521) and randomly selected controls (n=932) from a geographically
      defined district in southern Finland were recruited. The risk of developing
      asthma was significantly higher among current smokers with an adjusted odds ratio
      (OR) of 1.33 (95% confidence interval 1.00-1.77) and among ex-smokers with an
      adjusted OR 1.49 (1.12-1.97) compared with never-smokers. Among current smokers,
      the risk increased up to 14 cigarettes x day(-1), and a similar trend was
      observed in relation to cumulative smoking. In conclusion, the current results
      support the hypothesis that smoking causes asthma in adulthood.

PMID- 15516666
TI  - Body mass index and asthma incidence among USA adults.
AB  - The aim of this study was to examine the association between body mass index
      (BMI) and asthma incidence. Data from the baseline examination conducted during
      1971-1975, and the first follow-up conducted during 1982-1984, of the National
      Health and Nutrition Examination Survey I Epidemiologic Follow-up Study (a cohort
      study) was used. Asthma was self-reported or reported by proxies. BMI was
      calculated from measured height and weight obtained during the baseline
      examination. Among 9,456 participants aged 25-74 yrs who were free of asthma at
      baseline, 317 participants reported a diagnosis of asthma during the follow-up
      interview. Compared with participants with a BMI of 18.5-<25.0 kg.m(-2), the odds
      ratio (OR) for those with a BMI of > or =35 kg x m(-2) was 1.87 (95% confidence
      interval (CI) 1.12-3.13). ORs were similar for males and females. However, only
      125 of the 298 participants who recalled a date of onset reported a diagnosis
      that occurred after their baseline examination. Among this group of participants,
      BMI was not significantly associated with asthma incidence (OR 1.52, 95% CI 0.62
      3.77). In conclusion, although obese people reported more "incident" asthma
      during follow-up, it remains unclear whether this represents reactivation of
      previously diagnosed asthma or the onset of new cases, and whether these new
      cases actually represent true asthma or respiratory symptoms misdiagnosed as
      asthma.

PMID- 15516667
TI  - Increased frequency of detection of Chlamydophila pneumoniae in asthma.
AB  - Previous studies have suggested that chronic Chlamydophila pneumoniae infection
      may play a role in the pathogenesis of asthma. However, most studies have been
      based on serology and have been unable to differentiate acute from chronic
      infection. The present authors assessed the presence of acute and chronic C.
      pneumoniae infection in 74 spouse pairs, each consisting of one atopic asthmatic
      and one nonatopic nonasthmatic. Nasal secretions were sampled every 2 weeks from
      October to December and actively replicating C. pneumoniae infection was detected
      by specific RT-PCR. C. pneumoniae was detected in 31 out of 709 samples analysed,
      23 (6.4%) were positive in 362 samples from asthmatic participants and in eight
      out of 347 (2.3%) samples from their normal spouses (with a significant
      difference in infection rates, 95% confidence interval: 4.2%, 1.2-7.2%). A total
      of 16 (22%) asthmatic and seven (9%) normal participants were positive at least
      once during the study. These data confirm that Chlamydophila pneumoniae infection
      is detected more frequently among asthmatic participants than normal control
      participants. Further studies are required to confirm whether infections are also
      present in the lower airway and whether Chlamydophila pneumoniae infection plays
      a role in disease pathogenesis.

PMID- 15516668
TI  - Eosinophil degranulation status in allergic rhinitis: observations before and
      during seasonal allergen exposure.
AB  - Despite the fact that extensive degranulation is a likely prerequisite for a
      pathogenic role of eosinophils, little is known about the degranulation status of
      these cells in eosinophilic conditions. The present study of the ultrastructure
      of tissue eosinophils explores eosinophil degranulation in allergic rhinitis
      before and during seasonal allergen exposure. A total of 23 patients scored
      symptoms q.d., prior to and during the pollen season. The numbers of mucosal
      eosinophils and their degranulation status were determined in nasal biopsies.
      Furthermore, nasal lavage fluid levels of eosinophil cationic protein (ECP) and
      alpha2-macroglobulin were assessed as indices of eosinophil activity and plasma
      exudation, respectively. Seasonal allergen exposure was associated with increased
      nasal symptoms, increased lavage fluid levels of ECP and alpha2-macroglobulin,
      and increased numbers of tissue eosinophils. In the tissue, transmission electron
      microscopy revealed a moderate piecemeal degranulation already prior to the
      season (mean+/-sd 37+/-2.7% altered granules). Seasonal allergen exposure
      increased this degranulation (87+/-1.8%), and produced local areas with extensive
      deposition of granule proteins. The degree of eosinophil degranulation correlated
      with levels of ECP in lavage fluids obtained at histamine challenge. In
      conclusion, this study demonstrated that the nasal mucosa in allergic rhinitis
      features moderately degranulated eosinophils already at nonsymptomatic baseline
      conditions. In association with the development of symptomatic seasonal allergic
      rhinitis, the tissue deposition of eosinophil granule proteins is dramatically
      elevated through increased eosinophil numbers, together with markedly augmented
      degranulation of individual cells.

PMID- 15516669
TI  - Prevalence and rate of diagnosis of allergic rhinitis in Europe.
AB  - To measure the prevalence of allergic rhinitis among European adults and the
      proportion of undiagnosed subjects, a two-step, cross-sectional, population-based
      survey in Belgium, France, Germany, Italy, Spain, and the UK was undertaken. Step
      one of the study involved screening for allergic rhinitis by telephone interview,
      based on history of symptoms and/or self-awareness of the condition. Step two
      undertook confirmation of allergic rhinitis in a subset of the subjects screened
      positive; this was performed by a clinical diagnosis conducted in three to five
      clinical centres per country, including specific immunoglobulin E tests and a
      disease-specific questionnaire. A total of 9,646 telephone interviews were
      conducted between February and April 2001. Self-awareness of allergic rhinitis
      was reported by 19% of the subjects. Physician-based diagnosis of allergic
      rhinitis was reported by 13% of the subjects. In step two, 725 clinical
      assessments were conducted between May and August 2001. A total of 411 of
      patients, who underwent step two, had investigator-confirmed allergic rhinitis.
      Among patients with investigator-confirmed allergic rhinitis, 45% had not
      reported a previous diagnosis by a physician. Prevalence of subjects with
      clinically confirmable allergic rhinitis estimated by combining step one and step
      two data ranged from 17% in Italy to 29% in Belgium with an overall value of 23%.
      This large-scale study confirms that allergic rhinitis has a high prevalence in
      western Europe and is frequently undiagnosed.

PMID- 15516670
TI  - Manganese superoxide dismutase is increased in the airways of smokers' lungs.
AB  - Oxidant stress is a key mechanism for smoking-induced chronic obstructive
      pulmonary disease (COPD). Smoking has been shown to upregulate several
      antioxidant enzymes, with potential effects on the prevention of the disease
      and/or its progression. Superoxide dismutases (SOD)s are the only enzymes capable
      of consuming superoxide radicals. The purpose of the present study was to
      investigate SODs in the lungs of nonsmokers, smokers and COPD patients. Manganese
      superoxide dismutase (MnSOD), copper zinc SOD (CuZnSOD), and extracellular SOD
      (ECSOD), were investigated by immunohistochemistry in the airways of 13
      nonsmokers, 20 smokers and 22 COPD patients with mild-to-moderate disease. Lung
      tissue homogenates of three nonsmokers and four smokers were used for Western
      blot and enzyme activity analysis. The expression of MnSOD was higher in the
      central bronchial epithelium of smokers with COPD and in the alveolar epithelium
      of smokers without or with COPD than innonsmokers. Lung MnSOD immunoreactivity,
      evaluated by Western blotting and specific activity, were 33% and 51% higher,
      respectively, in smokers than in nonsmokers. No major changes could be observed
      in lung CuZnSOD or ECSOD immunoreactivities. Manganese superoxide dismutase is
      elevated in the alveolar epithelium of cigarette smokers, probably due to the
      increased oxidant burden in smokers' lungs.

PMID- 15516671
TI  - Enhanced PMN response in chronic bronchitis and community-acquired pneumonia.
AB  - Chronic bronchitis is a frequent underlying disease in community-acquired
      pneumonia (CAP). It is unclear to what extent an impaired or exaggerated innate
      immune response contributes to disease manifestations and severity. To assess the
      role of neutrophil activation and recruitment during acute pneumonic episodes,
      peripheral polymorphonulcear neutrophil (PMN) activation, chemotactic activity,
      interleukin-8 (CXCL-8) and CXCL-8 receptor (CXCR) expression and apoptosis rate
      were evaluated in CAP patients with and without chronic bronchitis. In addition,
      the expression of CXCRs and CXCL-8 was assessed on pulmonary neutrophils in
      chronic bronchitis patients to compare the activation of the chemokine system in
      different compartments. CAP severity was assessed by the simplified acute
      physiology score II and the prognosis of disease was assessed by the pneumonia
      severity index (PSI). An increased chemotactic activity of PMN from chronic
      bronchitis patients with CAP was found, which was not related to the expression
      of CXCRs. In addition, a decreased apoptosis rate of PMN was observed.
      Chemotactic activity was related to the PSI. Comparison of peripheral and
      pulmonary PMN revealed enhanced CXCL-8 levels and a decreased CXCR expression in
      the lung. In conclusion, neutrophil function in patients with chronic bronchitis
      and community-acquired pneumonia is characterised by an increased chemotactic
      activity combined with a decreased apoptosis rate. The downregulation of
      interleukin-8 receptors in the pulmonary compartment deserves further
      investigation.

PMID- 15516672
TI  - Severe community-acquired pneumonia: assessment of microbial aetiology as
      mortality factor.
AB  - Community-acquired pneumonia (CAP) remains a major cause of mortality. The
      aetiology of CAP has rarely been identified as a mortality risk factor. A
      prospective study was conducted to assess the prognostic factors of CAP patients
      admitted to the intensive care unit (Centre Hospitalier Departmental Felix Guyon,
      St Denis de la Reunion, France), with a special emphasis on microbial aetiology.
      All variables assessing severity were collected, with a special emphasis on
      microbial investigations. Among 112 immunocompetent patients (mean+/-SD age
      54.7+/-15.1 yrs), 84% were male. Severity of CAP was demonstrated by mortality
      rate (43%), shock (48%), simplified acute physiology score (SAPS; 46.4+/-21.6)
      and mechanical ventilation support (82%). Mean risk factor score was 2.2+/-1.2.
      Microbiological identification was obtained in 78.6% of cases, with positive
      blood culture in 33%. Most frequently, microbial agents were Streptococcus
      pneumoniae and Klebsiella pneumoniae (42% and 22%, respectively). The univariate
      analysis recorded the usual mortality variables: age, alcohol consumption, SAPS,
      shock, mechanical ventilation, positive end expiratory pressure level, positive
      blood culture, multilobar infiltrates on chest radiograph, neutropenia, and
      acidosis, and found K. pneumoniae (versus S. pneumoniae, and all CAP) as a
      mortality factor. The multivariate analysis demonstrated that septic shock
      (relative risk (RR) 141), K. pneumoniae CAP (RR 27), SAPS (RR 10.7) and positive
      blood culture (RR 2.7) were independent factors related to death. In conclusion,
      the present study found that the microbial aetiology, Klebsiella pneumoniae, was
      an independent risk factor for mortality in severe community-acquired pneumonia.

PMID- 15516673
TI  - Disturbed alveolar fibrin turnover during pneumonia is restricted to the site of
      infection.
AB  - Severe infection is associated with profound alterations in the systemic
      haemostatic balance, with activation of coagulation and suppressed fibrinolysis.
      Within the alveolar compartment, similar disturbances have been described during
      pulmonary inflammation. The current authors investigated whether local
      haemostasis was influenced during ventilator-associated pneumonia (VAP). In five
      patients with unilateral VAP, bronchoalveolar lavage fluid (BALF) was obtained
      from both the infected site (as identified on chest radiograph) and the
      contralateral noninfected lung (with no clinical or radiographic abnormalities).
      Markers for coagulation and fibrinolysis were compared between infected and
      noninfected lungs. A total of 10 healthy volunteers and 10 mechanically
      ventilated patients without pneumonia served as controls. Strong activation of
      coagulation (high levels of thrombin-antithrombin complexes, soluble tissue
      factor and factor VIIa) was detected in BALF from infected lungs, compared with
      that from noninfected lungs and controls. Furthermore, in infected lungs,
      fibrinolysis was depressed, with high levels of plasminogen activator inhibitor
      type 1. In conclusion, ventilator-associated pneumonia is characterised by a
      hypercoagulant state at the site of infection.

PMID- 15516674
TI  - Morning levels of fibrinogen in children with sleep-disordered breathing.
AB  - Elevated fibrinogen level is a predictor of cardiovascular disease in adults, and
      it is associated with sleep-disordered breathing. Levels of fibrinogen in adults
      are affected by other co-existing cardiovascular risk factors, which are not
      usually present in children. To investigate the association between fibrinogen
      and sleep-disordered breathing, a case-control study was carried out in children
      with and without habitual snoring. All snoring children underwent
      polysomnography. Morning fibrinogen values in 30 children with snoring and an
      apnoea-hypopnoea index (AHI) > or =5 episodes x h(-1) (median (interquartile
      range) 318 mg x dL(-1) (290-374)) were similar to values in 61 children with
      snoring and an AHI <5 episodes x h(-1) (307 (269-346)). Both groups had higher
      fibrinogen values than those in 23 controls without snoring (271 mg x dL(-1) (244
      294)). There was no correlation between fibrinogen values and AHI, respiratory
      movement/arousal index or haemoglobin desaturation index. In conclusion,
      fibrinogen values are higher in children with snoring than in controls, but there
      is no association between these values and polysomnography indices.

PMID- 15516675
TI  - Impaired pulmonary status in cystic fibrosis adults with two mutated MBL-2
      alleles.
AB  - Mannose-binding lectin has recently been identified as a modifier of severity in
      cystic fibrosis, although studies have produced differing results and the
      mechanism of action remains unclear. The current authors have studied large
      cohorts of adults (n=298) and children (n=260) to explore this apparent
      relationship further. Adults with two structural mutations, but not
      heterozygotes, had significantly reduced lung function and oxygen saturations,
      more frequent hospital admissions and raised systemic inflammatory markers. This
      was not related to increased rates of infection with Pseudomonas aeruginosa, and
      there was no increased susceptibility to Burkholderia cepacia. None of these
      findings was mirrored in the paediatric cohort. In conclusion, severe mannose
      binding lectin deficiency appears to be detrimental to cystic fibrosis adults,
      although heterozygotes are not affected. It is suggested that this is not related
      to impaired complement-mediated bacterial killing, and a link with the host
      inflammatory response is hypothesised. If mannose-binding lectin replacement is
      developed as a new approach to treatment for this disease, the present study
      would suggest that the small group of severely deficient patients with two
      structural mutations may be the group to benefit.

PMID- 15516676
TI  - Effects of acute hypovolaemia by furosemide on tracheal transepithelial potential
      difference and mucus in dogs.
AB  - Furosemide is a potent diuretic that affects water transfer across the
      respiratory epithelium, which is closely related to the transepithelial potential
      difference (PD). Water is a critical factor that determines mucus transport; an
      important lung defence mechanism that removes particles and microorganisms from
      the respiratory system. The aim of the present study was to investigate the acute
      effects of furosemide and hypovolaemia on tracheal PD and mucus properties. A
      total of 36 male mixed-breed dogs were submitted to anaesthesia, mechanical
      ventilation and haemodynamic monitoring. They were randomly assigned to three
      groups consisting of: a control group, a furosemide (40 mg i.v.) + hypovolaemia
      group, and a furosemide (40 mg i.v.) + volume replacement group. Tracheal PD and
      mucus samples were collected at time 0, 1 and 2 h after intervention. Mucus
      properties were analysed by means of a magnetic microrheometer and in vitro
      mucociliary transportability on the frog palate. Compared to controls, furosemide
      decreased PD to intermediate values, and only significantly when associated with
      hypovolaemia (-13+/-5 and -8+/-2 mV, time 0 and 2 h, respectively). In addition
      to the direct effect of furosemide, these results indicate that hypovolaemia also
      affects ion transport in the tracheal membrane. Furosemide and hypovolemia have
      no acute effects on respiratory mucus properties.

PMID- 15516677
TI  - No serological evidence of Rickettsia helvetica infection in Scandinavian
      sarcoidosis patients.
AB  - Many agents have been suggested to elicit sarcoidosis, and, recently, an
      association was presented between this disease and the bacterium Rickettsia
      helvetica. The aim of this study was to investigate if serological support for
      such an association could be detected. Sera from 20 well-characterised
      sarcoidosis patients were investigated for anti-rickettsial immunoglobulin G
      antibodies with a micro-immunofluorescence technique. R. helvetica, R. conorii
      and R. typhi served as antigens. In conclusion, none of the investigated sera
      displayed detectable titres of anti-rickettsial immunoglobulin G antibodies.
      Thus, the current study does not support an association between rickettsia and
      sarcoidosis.

PMID- 15516678
TI  - Assessment of 18F-fluorodeoxyglucose dual-head gamma camera in asbestos lung
      diseases.
AB  - The purpose of this study was to evaluate the performance of 18F
      fluorodeoxyglucose (18FDG) imaging via coincidence detection emission tomography
      (CDET) in identifying malignant lesions in subjects exposed to asbestos. A total
      of 30 patients exposed to asbestos underwent 18FDG-CDET between January 2000 and
      June 2003. A CDET scan of the thorax and abdomen was performed 60 min after
      injection of 18FDG in fasting patients, and results were obtained in slices in
      three axes. The CDET results were compared to those from computed tomography
      (CT), and pleural or surgical biopsy in patients with positive 18FDG-CDET
      results. All primary malignant mesotheliomas accumulated 18FDG (n=6), and, in two
      patients, CDET findings were superior to those of CT, allowing early detection.
      In two cases, lung carcinomas with malignant pleural effusion were also detected.
      There were five false positive CDET results: three unilateral pleural thickening,
      one rounded atelectasis, and one benign lung nodule. All patients with pleural
      plaques showed no significant 18FDG uptake. Malignant diseases were detected by
      18FDG-CDET imaging with a sensitivity of 89% and specificity of 71%. Coincidence
      detection emission tomography can identify malignant mesothelioma in selected
      subjects exposed to asbestos. Coincidence detection emission tomography appears
      to be a useful noninvasive method for the follow-up of subjects with exposure
      risk of asbestosis.

PMID- 15516679
TI  - Asthma and cigarette smoking.
AB  - In most developed countries approximately 25% of adults with asthma are current
      cigarette smokers. Asthma and active cigarette smoking interact to cause more
      severe symptoms, accelerated decline in lung function, and impaired short-term
      therapeutic response to corticosteroids. Cigarette smoking may modify
      inflammation that is associated with asthma, although there is limited published
      data on airway pathology in smokers with asthma. To date, the evidence points
      towards a combination of both heightened and suppressed inflammatory responses in
      smokers compared with nonsmokers with asthma. The mechanisms of corticosteroid
      resistance in asthmatic smokers are unexplained, but could be as a result of
      alterations in airway inflammatory cell phenotypes (e.g. increased neutrophils or
      reduced eosinophils), changes in the glucocorticoid receptor-alpha to -beta ratio
      (e.g. overexpression of glucocorticoid receptor beta), and increased activation
      of pro-inflammatory transcription factors (e.g. nuclear factor-kappaB) or reduced
      histone deacetylase activity. In conclusion, every effort should be made to
      encourage asthmatics who smoke to stop, although the effects of smoking cessation
      upon reversing the adverse effects of tobacco smoke on asthma control,
      therapeutic response to corticosteroids and airway pathology have yet to be fully
      elucidated. Alternative or additional therapies to inhaled corticosteroids are
      needed for asthmatic patients who are unable to quit smoking.

PMID- 15516680
TI  - Azithromycin for cystic fibrosis.
AB  - During what is a relatively barren time for new therapies for cystic fibrosis
      (CF), azithromycin has received a lot of attention as a potential treatment for
      CF lung disease. Laboratory studies suggest that azithromycin may have indirect
      actions, including anti-inflammatory, in addition to the standard antibacterial
      properties. The unique pharmacokinetics of azithromycin sets it aside from other
      macrolide antibiotics, but may result in increased resistance patterns. Three
      well-designed randomised controlled trials have demonstrated a small but
      significant improvement in respiratory function (forced expiratory volume in one
      second) with azithromycin compared with placebo. These trial results are
      confirmed by a recent meta-analysis. Mild adverse events (wheeze, diarrhoea and
      nausea) were significantly increased in one trial. There is no clear consensus
      regarding the correct dose and length of treatment with azithromycin. The present
      review discusses the role of azithromycin in the management of cystic fibrosis
      and the need for close monitoring of patients started on this drug. In addition,
      clinics should liaise closely with their microbiology departments and monitor
      resistance patterns.

PMID- 15516681
TI  - Paediatric lung transplantation.
AB  - Since 1990, lung transplantation has been performed in infants, children and
      adolescents in small numbers, and the numbers, in comparison with adult
      transplants, remain small today. The indications for lung transplantation are
      similar in childhood when compared with adults, but the disease entities are
      distinct. In children, severe pulmonary vascular disease is most commonly
      associated with developmental abnormalities or congenital heart disease, as
      opposed to idiopathic pulmonary hypertension. Cystic fibrosis is the dominant
      indication for lung transplantation in older childhood and adolescence. The
      operative approach to lung transplantation in early life differs from that in
      adults, in that cardiopulmonary bypass is more likely to be utilised and
      bilateral lung transplantation is strongly preferred to single lung
      transplantation. Living donor lung transplantation is proportionately more common
      in children and adolescents than in adults. Post-transplant complications related
      to viral infection and post-transplant lymphoproliferative disease are more
      common and more likely to be severe and life-threatening. Bronchiolitis
      obliterans is the most important complication after paediatric lung
      transplantation and limits both the quality of life and duration of survival, as
      in adults.

PMID- 15516682
TI  - Magnetic stimulation for the measurement of respiratory and skeletal muscle
      function.
AB  - Respiratory and skeletal muscle function is of interest in many areas of
      pulmonary and critical care medicine. The capacity of the respiratory muscle pump
      to respond to the load imposed by disease is the basis of an understanding of
      ventilatory failure. Over the last four decades, considerable progress has been
      made in quantifying the capacity of the respiratory muscles, in terms of
      strength, endurance and fatigue. With the development of magnetic stimulation, it
      has recently become possible to nonvolitionally assess the respiratory muscles in
      a clinically acceptable way. This is of particular interest in the investigation
      of patients receiving critical care, those with neuromuscular disease, and in
      children where volitional efforts are either not possible or likely to be sub
      maximal. Furthermore, the adaptation of these techniques to quantify the strength
      of peripheral muscles, such as the quadriceps, has allowed the effects of muscle
      training or rehabilitation, uninfluenced by learning effect, to be assessed. This
      article focuses on the physiological basis of magnetic nerve stimulation, and
      reviews how the technique has been applied to measure muscle strength and
      fatigue, with particular emphasis upon the diaphragm. The translation of magnetic
      stimulation into a clinical tool is described, and how it may be of diagnostic,
      prognostic and therapeutic value in several areas of pulmonary medicine. In
      particular, the use of magnetic stimulation in neuromuscular disease, the
      intensive care setting, chronic obstructive pulmonary disease and paediatrics
      will be discussed.

PMID- 15516683
TI  - Pulmonary-Hepatic vascular Disorders (PHD).

PMID- 15516684
TI  - Nasal nitric oxide is low early in life: case study of two infants with primary
      ciliary dyskinesia.
AB  - Nasal nitric oxide levels are low in patients with primary ciliary dyskinesia,
      but it is not known whether this defect is already present in the first months of
      life. The current authors measured nasal nitric oxide in two infants with situs
      inversus and primary ciliary dyskinesia, diagnosed by electron microscopy at 4
      and 6 months of age, and in five healthy control infants. Nasal nitric oxide
      values in the primary ciliary dyskinesia infants (85 and 115 parts per billion
      (ppb)) were markedly lower than in the healthy controls (mean: 295 ppb, range:
      225-379 ppb). This is the first report to show that nasal nitric oxide values are
      already low in early life in primary ciliary dyskinesia children, supporting the
      hypothesis that a reduced production of nasal nitric oxide is an intrinsic
      feature of this disease. The current authors suggest that the nasal nitric oxide
      test may be a useful, noninvasive method for screening young children for primary
      ciliary dyskinesia in clinical practice.

PMID- 15516685
TI  - Severe breathlessness, mouth ulcers and skin blistering in a female.

PMID- 15516686
TI  - Should patients with lymphangioleiomyomatosis undergo screening for meningioma?

PMID- 15516687
TI  - Strategies to increase the lung donors' pool.

PMID- 15516688
TI  - End points for pulmonary arterial hypertension: a way backward.

PMID- 15516689
TI  - Nucleosome assembly protein 1 exchanges histone H2A-H2B dimers and assists
      nucleosome sliding.
AB  - Eukaryotic chromatin is highly dynamic and turns over rapidly even in the absence
      of DNA replication. Here we show that the acidic histone chaperone nucleosome
      assembly protein 1 (NAP-1) from yeast reversibly removes and replaces histone
      protein dimer H2A-H2B or histone variant dimers from assembled nucleosomes,
      resulting in active histone exchange. Transient removal of H2A-H2B dimers
      facilitates nucleosome sliding along the DNA to a thermodynamically favorable
      position. Histone exchange as well as nucleosome sliding is independent of ATP
      and relies on the presence of the C-terminal acidic domain of yeast NAP-1, even
      though this region is not required for histone binding and chromatin assembly.
      Our results suggest a novel role for NAP-1 (and perhaps other acidic histone
      chaperones) in mediating chromatin fluidity by incorporating histone variants and
      assisting nucleosome sliding. NAP-1 may function either untargeted (if acting
      alone) or may be targeted to specific regions within the genome through
      interactions with additional factors.

PMID- 15516690
TI  - Specific inhibition and stabilization of aspergilloglutamic peptidase by the
      propeptide. Identification of critical sequences and residues in the propeptide.
AB  - Aspergilloglutamic peptidase (formerly called aspergillopepsin II) is an acid
      endopeptidase produced by Aspergillus niger var. macrosporus, with a novel
      catalytic dyad of a glutamic acid and a glutamine residue, thus belonging to a
      novel peptidase family G1. The mature enzyme is generated from its precursor by
      removal of the putative 41-residue propeptide and an 11-residue intervening
      peptide through autocatalytic activation. In the present study, the propeptide
      (Ala1-Asn41) and a series of its truncated peptides were chemically synthesized,
      and their effects on the enzyme activity and thermal stability were examined to
      identify the sequences and residues in the propeptide most critical to the
      inhibition and thermal stabilization. The synthetic propeptide was shown to be a
      potent competitive inhibitor of the enzyme (Ki = 27 nM at pH 4.0). Various
      shorter propeptide fragments derived from the central region of the propeptide
      had significant inhibitory effect, whereas their Ala scan-substituted peptides,
      especially R19A and H20A, showed only weak inhibition. Substitution of the Pro23
      Pro24 sequence near His20 with an Ala-Ala sequence changed the peptide Lys18
      Tyr25 to a substrate with His20 as the P1 residue. Furthermore, the propeptide
      was shown to be able to significantly protect the enzyme from thermal
      denaturation (DeltaTm = approximately 19 degrees C at pH 5.6). The protective
      potencies of the propeptide as well as truncated propeptides and their Ala scan
      substituted peptides are parallel with their inhibitory potencies. These results
      indicate that the central part, and especially Arg19 and His20 therein, of the
      propeptide is most critical to the inhibition and thermal stabilization and that
      His20 interacts with the enzyme at or near the S1 site in a nonproductive
      fashion.

PMID- 15516691
TI  - Cooperativity between far upstream enhancer and proximal promoter elements of the
      human {alpha}2(I) collagen (COL1A2) gene instructs tissue specificity in
      transgenic mice.
AB  - Interaction between the proximal (-378) promoter and the far upstream (-20 kb)
      enhancer is essential for tissue-specific expression of the human alpha2(I)
      collagen gene (COL1A2) in transgenic mice. Previous in vitro studies have shown
      that three Sp1 binding sites (around -300) are part of a cytokine-responsive
      element and that two TC-rich boxes (around -160 and -125) and a CBF/NFY consensus
      sequence (around -80) confer optimal promoter activity by interacting among
      themselves and with the upstream Sp1 sites. Here we report that mutations of the
      Sp1 binding sites, TC-rich boxes or CBF/NFY consensus sequence lead to reduced
      transgene activity, thus underscoring the functional interdependence of the
      proximal promoter elements. Loss of the Sp1 binding sites was associated with
      loss of transgene expression in osteoblasts, whereas elimination of the CBF/NFY
      binding site (alone or in combination with the TC-rich boxes) was correlated with
      a lack of activity in the ventral fascia and head dermis and musculature.
      Additionally, transgene expression in skin fascia fibroblasts depended on the
      integrity of the Sp1 binding sites and TC-rich boxes, and on their physical
      configuration. Evidence is also presented suggesting cooperativity between cis
      acting elements of the far upstream enhancer and proximal promoter in assembling
      tissue-specific protein complexes. This study thus reiterates the complex and
      highly combinatorial nature of the regulatory network governing COL1A2
      transcription in vivo.

PMID- 15516692
TI  - Cloning and functional analysis of the rhesus macaque ABCG2 gene. Forced
      expression confers an SP phenotype among hematopoietic stem cell progeny in vivo.
AB  - Hematopoietic cells can be highly enriched for repopulating ability based upon
      the efflux of the fluorescent Hoechst 33342 dye by sorting for SP (side
      population) cells, a phenotype attributed to expression of ABCG2, a member of the
      ABC transporter superfamily. Intriguingly, murine studies suggest that forced
      ABCG2 expression prevents hematopoietic differentiation. We cloned the full
      length rhesus ABCG2 and introduced it into a retroviral vector. ABCG2-transduced
      human peripheral blood progenitor cells (PBPCs) acquired the SP phenotype but
      showed significantly reduced growth compared with control. Two rhesus macaques
      received autologous PBPCs split for transduction with the ABCG2 or control
      vectors. Marking levels were similar between fractions with no discrepancy
      between bone marrow and peripheral blood marking. Analysis for the SP phenotype
      among bone marrow and mature blood populations confirmed ABCG2 expression at
      levels predicted by vector copy number long term, demonstrating no block to
      differentiation in the large animal. In vitro studies showed selective protection
      against mitoxantrone among ABCG2-transduced rhesus PBPCs. Our results confirm the
      existence of rhesus ABCG2, establish its importance in conferring the SP
      phenotype, suggest no detrimental effect of its overexpression upon
      differentiation in vivo, and imply a potential role for its overexpression as an
      in vivo selection strategy for gene therapy applications.

PMID- 15516693
TI  - The hTERT gene is embedded in a nuclease-resistant chromatin domain.
AB  - Normal human cells rarely undergo spontaneous immortalization. Given that ectopic
      expression of the human telomerase catalytic subunit hTERT leads to cellular
      immortalization, the endogenous hTERT gene is likely constitutively repressed.
      Hence, we have examined the chromatin structure of the native hTERT locus and the
      neighboring loci, CRR9 and Xtrp2, in normal human fibroblasts and a set of
      immortal lines. Using generalized DNase I sensitivity assays, we revealed that
      the entire hTERT gene was embedded in a chromatin domain that was as resistant to
      the nuclease as the well studied beta-globin loci in both telomerase-positive and
      -negative cells. This condensed domain was at least 100 kb in size and contained
      the intergenic region 5' to the hTERT gene and the downstream Xtrp2 locus. A
      transition from the nuclease-sensitive CRR9 locus to the condensed region
      appeared near the 3'-end of the CRR9 gene. hTERT transcription was associated
      with the appearance of a major DNase I-hypersensitive site positioned around the
      hTERT transcription start site and several minor hypersensitive sites. In
      telomerase-negative cells, the inhibition of histone deacetylases by trichostatin
      A led to the opening of this chromatin domain, accompanied by transcription from
      the hTERT gene but not the Xtrp2 gene. In contrast, the inhibition of protein
      synthesis by cycloheximide induced transcription from both the hTERT and Xtrp2
      genes, indicating that histone deacetylases and labile factors coordinate to
      silence this chromosomal region. Taken together, our data suggest a novel
      mechanism of hTERT regulation at the chromatin level and have important
      implications for studying telomerase expression.

PMID- 15516694
TI  - Membrane type 1-matrix metalloproteinase is regulated by chemokines monocyte
      chemoattractant protein-1/ccl2 and interleukin-8/CXCL8 in endothelial cells
      during angiogenesis.
AB  - We have investigated the putative role and regulation of membrane type 1-matrix
      metalloproteinase (MT1-MMP) in angiogenesis induced by inflammatory factors of
      the chemokine family. The absence of MT1-MMP from null mice or derived mouse lung
      endothelial cells or the blockade of its activity with inhibitory antibodies
      resulted in the specific decrease of in vivo and in vitro angiogenesis induced by
      CCL2 but not CXCL12. Similarly, CCL2- and CXCL8-induced tube formation by human
      endothelial cells (ECs) was highly dependent on MT1-MMP activity. CCL2 and CXCL8
      significantly increased MT1-MMP surface expression, clustering, activity, and
      function in human ECs. Investigation of the signaling pathways involved in
      chemokine-induced MT1-MMP activity in ECs revealed that CCL2 and CXCL8 induced
      cortical actin polymerization and sustained activation of phosphatidylinositol 3
      kinase (PI3K) and the small GTPase Rac. Inhibition of PI3K or actin
      polymerization impaired CCL2-induced MT1-MMP activity. Finally, dimerization of
      MT1-MMP was found to be enhanced by CCL2 in ECs in a PI3K- and actin
      polymerization-dependent manner. In summary, we identify MT1-MMP as a molecular
      target preferentially involved in angiogenesis mediated by CCL2 and CXCL8, but
      not CXCL12, and suggest that MT1-MMP dimerization might be an important mechanism
      of its regulation during angiogenesis.

PMID- 15516695
TI  - Involvement of NADPH in the interaction between heme oxygenase-1 and cytochrome
      P450 reductase.
AB  - Heme oxygenase-1 (HO-1) catalyzes the physiological degradation of heme at the
      expense of molecular oxygen using electrons donated by NADPH-cytochrome P450
      reductase (CPR). In this study, we investigated the effect of NADP(H) on the
      interaction of HO-1 with CPR by surface plasmon resonance. We found that HO-1
      associated with CPR more tightly in the presence of NADP(+) (K(D) = 0.5 microm)
      than in its absence (K(D) = 2.4 microm). The HO-1 mutants, K149A, K149A/K153A,
      and R185A, showed almost no heme degradation activity with NADPH-CPR, whereas
      they exhibited activity comparable to that of the wild type when sodium ascorbate
      was used. R185A showed a 100-fold decreased affinity for CPR compared with wild
      type, even in the presence of NADP(+) (K(D) = 36.3 microm). The affinities of
      K149A and K149A/K153A for CPR were decreased 7- and 9-fold (K(D) = 16.8 and 21.8
      microm), respectively. In contrast to R185A, the affinities of K149A and
      K149A/K153A were improved by the addition of NADP(+) (K(D) = 5.2 and 9.6 microm,
      respectively), as was the case with wild type. Computer modeling of the HO-1/CPR
      complex showed that the guanidino group of Arg(185) is located within the
      hydrogen bonding distance of 2'-phosphate of NADPH, suggesting that Arg(185)
      contributes to the binding to CPR through an electrostatic interaction with the
      phosphate group. On the other hand, Lys(149) is close to a cluster of acidic
      amino acids near the FMN binding site of CPR. Thus, Lys(149) and Lys(153) appear
      to interact with CPR in such a way as to orient the redox partners for optimal
      electron transfer from FMN of CPR to heme of HO-1.

PMID- 15516696
TI  - Angiotensin-receptor blockade versus converting-enzyme inhibition in type 2
      diabetes and nephropathy.
AB  - BACKGROUND: Few studies have directly compared the renoprotective effects of
      angiotensin II-receptor blockers and angiotensin-converting-enzyme (ACE)
      inhibitors in persons with type 2 diabetes. METHODS: In this prospective,
      multicenter, double-blind, five-year study, we randomly assigned 250 subjects
      with type 2 diabetes and early nephropathy to receive either the angiotensin II
      receptor blocker telmisartan (80 mg daily, in 120 subjects) or the ACE inhibitor
      enalapril (20 mg daily, in 130 subjects). The primary end point was the change in
      the glomerular filtration rate (determined by measuring the plasma clearance of
      iohexol) between the baseline value and the last available value during the five
      year treatment period. Secondary end points included the annual changes in the
      glomerular filtration rate, serum creatinine level, urinary albumin excretion,
      and blood pressure; the rates of end-stage renal disease and cardiovascular
      events; and the rate of death from all causes. RESULTS: After five years, the
      change in the glomerular filtration rate was -17.5 ml per minute per 1.73 m2
      (where the minus sign denotes a decrement) in the telmisartan-treated subjects,
      as compared with -15.0 ml per minute per 1.73 m2 in the enalapril-treated
      subjects; the treatment difference was thus -2.6 ml per minute per 1.73 m2 (95
      percent confidence interval, -7.1 to 2.0 ml per minute per 1.73 m2)[corrected]
      The lower boundary of the confidence interval, in favor of enalapril, was greater
      than the predefined margin of -10.0 ml per minute per 1.73 m2, indicating that
      telmisartan was not inferior to enalapril. The effects of the two agents on the
      secondary end points were not significantly different after five years.
      CONCLUSIONS: Telmisartan is not inferior to enalapril in providing long-term
      renoprotection in persons with type 2 diabetes. These findings do not necessarily
      apply to persons with more advanced nephropathy, but they support the clinical
      equivalence of angiotensin II-receptor blockers and ACE inhibitors in persons
      with conditions that place them at high risk for cardiovascular events.

PMID- 15516697
TI  - Preventing microalbuminuria in type 2 diabetes.
AB  - BACKGROUND: The multicenter double-blind, randomized Bergamo Nephrologic Diabetes
      Complications Trial (BENEDICT) was designed to assess whether angiotensin
      converting-enzyme inhibitors and non-dihydropyridine calcium-channel blockers,
      alone or in combination, prevent microalbuminuria in subjects with hypertension,
      type 2 diabetes mellitus, and normal urinary albumin excretion. METHODS: We
      studied 1204 subjects, who were randomly assigned to receive at least three years
      of treatment with trandolapril (at a dose of 2 mg per day) plus verapamil
      (sustained-release formulation, 180 mg per day), trandolapril alone (2 mg per
      day), verapamil alone (sustained-release formulation, 240 mg per day), or
      placebo. The target blood pressure was 120/80 mm Hg. The primary end point was
      the development of persistent microalbuminuria (overnight albumin excretion, > or
      =20 microg per minute at two consecutive visits). RESULTS: The primary outcome
      was reached in 5.7 percent of the subjects receiving trandolapril plus verapamil,
      6.0 percent of the subjects receiving trandolapril, 11.9 percent of the subjects
      receiving verapamil, and 10.0 percent of control subjects receiving placebo. The
      estimated acceleration factor (which quantifies the effect of one treatment
      relative to another in accelerating or slowing disease progression) adjusted for
      predefined baseline characteristics was 0.39 for the comparison between verapamil
      plus trandolapril and placebo (P=0.01), 0.47 for the comparison between
      trandolapril and placebo (P=0.01), and 0.83 for the comparison between verapamil
      and placebo (P=0.54). Trandolapril plus verapamil and trandolapril alone delayed
      the onset of microalbuminuria by factors of 2.6 and 2.1, respectively. Serious
      adverse events were similar in all treatment groups. CONCLUSIONS: In subjects
      with type 2 diabetes and hypertension but with normoalbuminuria, the use of
      trandolapril plus verapamil and trandolapril alone decreased the incidence of
      microalbuminuria to a similar extent. The effect of verapamil alone was similar
      to that of placebo.

PMID- 15516698
TI  - Treating diabetic nephropathy--are there only economic issues?

PMID- 15516699
TI  - Trace element status (Se, Cu, Zn) in healthy Portuguese subjects of Lisbon
      population: a reference study.
AB  - Serum levels of selenium, copper, and zinc were systematically determined in
      healthy subjects of the Lisbon population. The sample consisted of 183 blood
      donors of both genders who were divided into two age groups: 20-44 and 45-70 yr
      of age; relationships with gender, age, the lipid profile, and tobacco
      consumption were investigated. In the female group, the intake of oral
      contraceptives and pregnancy were considered for the youngest women, and hormonal
      replacement therapy (HRT) was taken into account for the oldest ones. Serum
      concentrations of these elements were in the same range as those found for
      populations of other European countries. Differences between genders were
      observed for the three elements studied, with serum selenium and zinc
      concentrations higher in men and copper levels higher in women. Age-dependent
      differences were found for selenium: The oldest subjects (regardless gender)
      presented the highest concentrations of selenium in serum as further demonstrated
      by the positive correlation with age. In both pregnant and contraceptive-using
      women, copper was greatly increased, confirming the influence of estrogen status
      and/or oral contraceptive intake on increased serum copper levels. However, in
      postmenopausal women, HRT did not significantly affect serum copper levels.
      Selenium, copper, and zinc status were not different between normolipidemic and
      hyperlipidemic subjects for the same gender and age range, but selenium levels
      tended to increase with hyperlipidemia when considering the whole group of
      subjects. With respect to the lifestyle, higher serum zinc levels were found in
      tobacco-consuming men. Albumin serum levels were similar for all considered
      subgroups, except for the pregnant women, for whom a decrease in this parameter
      was observed. The present study allowed one to obtain reference values for this
      healthy group of population, which will serve for a comparative study with groups
      having pathological conditions, such as cardiovascular disease.

PMID- 15516700
TI  - Effect of chromium and zinc on insulin signaling in skeletal muscle cells.
AB  - Patients on total parenteral nutrition without Cr supplementation develop
      symptoms similar to those of diabetes. Zn has been implicated in diabetes because
      of its antioxidant properties and interaction with insulin. To study the effect
      of these metal ions on insulin signaling proteins, cultured mouse skeletal muscle
      cells was used as an in vitro model, as the tissue accounts for more than 80% of
      insulin-stimulated glucose disposal in the body. In the present study, it has
      been observed that both Cr and Zn, upon prolonged exposure, could stimulate
      tyrosine phosphorylation of insulin receptor (IR) even in the absence of insulin.
      Insulin-mediated IR tyrosine phosphorylation was enhanced by the treatment with
      both of the metal ions. Both Cr and Zn could phosphorylate insulin receptor
      substrate-1 (IRS-1). Phosphorylation of IRS-1 induced by metal ions was higher
      than that induced by insulin. Hence, both Cr and Zn were found to have insulin
      mimetic activity. Both of the metal ions were also found to potentiate insulin
      mediated activation of IRS-1. The basal level of glucose uptake was also
      increased by prolonged treatment of the cells with the metal ions. The ions could
      also enhance the insulin-stimulated glucose uptake into the cells. Therefore,
      both Zn and Cr seem to have a positive effect on insulin signaling leading to
      glucose uptake.

PMID- 15516701
TI  - Effect of hormone replacement therapy on the elemental contents of uterine
      tissue.
AB  - For the past years, different therapies based on steroid hormone supplementation
      or modulators of estrogen receptors have been used after menopause to prevent or
      manage osteoporosis. Although these treatments seem to be beneficial, they have
      some negative effects in the uterus and breast. The objective of this study was
      to assess variations for the concentrations of K, Ca, Mn, Fe, Cu, Zn, and Se in
      uterine tissue of Wistar rats. Ovariectomized rats were subjected to estrogen,
      progesterone, raloxifene, and tibolone supplementation and compared with
      nonovariectomized control animals. Elemental contents determined by the particle
      induced X-ray emission (PIXE) technique revealed major alterations in Fe, Ca, Mn,
      and Se in the uterus of ovariectomized rats relative to control animals. After
      ovariectomy, a significant increase in Ca and Fe and a significant decrease in Mn
      and Se contents were determined in the uterus. For the ovariectomized groups in
      which animals received raloxifene, tibolone, estrogen, and estrogen combined with
      progesterone supplementation, an overall recovery in Mn, Fe, and Se contents was
      verified. Elemental concentration in the progesterone-supplemented group did not
      significantly differ from ovariectomized animals receiving placebo. The
      alterations found for ovariectomized animals receiving placebo and progesterone
      suggest tissue impairment and trace element imbalance, contrasting with the
      remaining supplemented groups where an enhancement of tissue activity might
      justify similar concentration levels relative to controls, because most of the
      elemental contents altered after ovariectomy.

PMID- 15516702
TI  - Age-related changes of elements and relationships among elements in the common
      bile and pancreatic ducts.
AB  - To elucidate compositional changes of the common bile and main pancreatic ducts
      with aging, the authors investigated age-related changes of element contents in
      the common bile and pancreatic ducts by inductively coupled plasma-atomic
      emission spectrometry. After ordinary dissection by medical students was
      finished, the common bile ducts and main pancreatic ducts (pancreatic ducts) were
      resected and the element contents were determined. The Mg content increased
      significantly only in the pancreatic duct with aging, but the other element
      contents did not change significantly in both the common bile and pancreatic
      ducts with aging. Regarding the relationships among the elements, significant
      direct correlations were found among the contents of Ca, P, S, and Mg in the
      common bile ducts, with some exceptions between P and either S or Mg contents. In
      the pancreatic ducts, significant direct correlations were found between S and Mg
      contents and between P and Na contents. The relationships in the elements between
      the common bile and pancreatic ducts were examined. It was found that there were
      significant direct correlations in the Ca, Mg, and Fe contents between the common
      bile and pancreatic ducts; that is, as Ca, Mg, and Fe increased in the common
      bile duct, they increased simultaneously in the pancreatic duct.

PMID- 15516703
TI  - Distribution patterns of trace metals and of lipid peroxidation in plasma and
      erythrocytes of rat exposed to aluminum.
AB  - Significant decreases of the hematocrit, hemoglobin, and plasma iron levels were
      observed in rats receiving daily intraperitoneal injections of aluminum at a dose
      of 27 mg Al/kg body wt for 3 wk, as compared to untreated controls. The activity
      of alkaline phosphatase was also significantly lower in the treated animals as a
      result of the accumulation of aluminum in the liver (p<0.05). Following aluminum
      administration, the plasma concentrations of aluminum and copper were also
      significantly increased, whereas the plasma zinc levels and oxidative stress
      measured through thiobarbituric acid reaction products showed nonsignificant
      differences between the two groups (p>0.05). The erythrocyte concentrations of
      aluminum, copper, zinc, and iron and of superoxide dismutase activity were found
      to be significantly higher in the study group as compared to controls. The
      treated animals also showed evidence of higher oxidative stress in comparison to
      controls. These results suggest that erythrocyte aluminum accumulation could
      result in abnormal trace element homeostasis and increasing oxidative stress,
      which might be a mechanism of aluminum-induced anemia.

PMID- 15516704
TI  - Selenium protects cerebral ischemia in rat brain mitochondria.
AB  - Normal cellular metabolism produces oxidants that are neutralized by the cells'
      antioxidant enzymes and antioxidants taken from outside. An imbalance between
      oxidant and antioxidant has been postulated to lead to the neurodegeneration in
      the ischemic condition. In this study, we have demonstrated the prevention or
      slowdown of neuronal injury in middle cerebral artery occlusion (MCAO) by sodium
      selenite. Rats were pretreated with 0.05, 0.1, and 0.2 mg/kg body wt of sodium
      selenite for 7 d. The rats of group I (sham) and group II (ischemia) were
      pretreated with physiological saline for 7 d. On d 8, MCAO was induced for 2 h in
      the right side of brain of group II, III, IV, and V rats. Brains were dissect out
      after 22 h of reperfusion and washed with chilled physiological saline. The right
      cerebral hemisphere was used for the preparation of mitochondria. The activity of
      superoxide dismutase, catalase, glutathione peroxidase, glutathione-S
      transferase, and monoamine oxidase (MAO-A and MAO-B) was depleted significantly;
      conversely, the activity of poly(ADP-ribosyl) polymerase was elevated
      significantly as compared to the sham, and the pretreatment of the animals with
      different doses of sodium selenite has protected the activity of these enzymes
      significantly. The content of glutathione was decreased significantly, whereas
      the level of lipid peroxidation was increased significantly in the mitochondria
      of MCAO as compared to the sham group, and pretreatment with different doses of
      sodium selenite has protected their levels significantly as compared to the MCAO
      group. It is concluded that selenium, which is an essential part of our diet,
      might be helpful in protection against neurodegeneration in cerebral ischemia.

PMID- 15516705
TI  - Effect of bis(acetato)tetrakis(imidazole) copper(II) in delaying the onset and
      reducing the mortality rate of strychnine- and thiosemicarbazide- induced
      convulsions.
AB  - The anticonvulsant activity of bis(acetato)tetrakis(imidazole) copper(II),
      Cu(OAc)2(Im)4, was studied in normal mice using chemical convulsions induced by
      strychnine, thiosemicarbazide, picrotoxin, and pentelenetetrazol. Intraperitoneal
      administration of Cu(OAc)2(Im)4, 50 mg/kg body mass, has delayed the onset of
      strychnine (3 mg/kg)-induced convulsion by 204% (p < or = 0.005) and
      thiosemicarbazide (20 mg/kg)-induced convulsant by 61% (p < or = 0.005). The
      changes in the onset of picrotoxin- (6 mg/kg) and pentelenetetrazol (50 mg/kg)
      induced convulsions were not significant. The same dosage of the copper compound
      was effective in delaying the lethal time and reducing the mortality rate of
      treated animals. The anticonvulsant activity of Cu(OAc)2(Im)4 complex against
      strychnine was not related to its constituents because the inorganic form of
      copper such as copper chloride, copper acetate, and the parent imidazole has no
      anticonvulsant activity. Other copper(II) complexes like copper(II)aspirinate and
      bis(acetato)bis(2-methyl imidazole) copper(II) were less effective.

PMID- 15516706
TI  - Unwelcome guests with master keys: how HIV enters cells and how it can be
      stopped.
AB  - HIV entry to host cells begins with binding of the viral envelope protein to CD4
      molecules on the host cell surface. This binding initiates conformational changes
      in the envelope protein that result in binding to a coreceptor (CCR5 or CXCR4),
      exposure of a previously hidden domain in the viral protein, insertion of a viral
      fusion peptide into the host-cell membrane and fusing the viral and cell
      membranes. Each of these steps provides an opportunity for intervention to
      prevent viral entry, and a number of agents targeting these steps are in
      development. Studies of coreceptor inhibitors and fusion inhibitors have
      indicated the presence of host and viral factors that can result in variability
      of antiretroviral effect. Improved understanding of these factors will help to
      guide clinical use of these new agents. This article summarizes a presentation by
      Robert W. Doms, MD, PhD, at the International AIDS Society-USA course in Chicago
      in May 2004.

PMID- 15516707
TI  - HIV and sexually transmitted diseases: lethal synergy.
AB  - Sexually transmitted diseases (STDs) can increase risk for acquisition and
      transmission of HIV via a number of mechanisms, including breaching of mechanical
      barriers to infection, increased inflammation and higher levels of HIV cellular
      targets, and increased genital tract HIV levels. Studies in Malawi clinic
      populations indicate that treatment of STDs can reduce genital tract HIV levels.
      Work in Africa and India has indicated that genital herpes infection is
      associated with increased risk of acquisition of HIV and that presence of genital
      ulcer disease is associated with increased risk of transmission of HIV disease.
      Acute HIV infection has been found to be more frequent in individuals with active
      STDs, and co-transmission may be a common phenomenon. Acute HIV infection, which
      is not currently routinely diagnosed, is associated with increased risk of
      transmission. Greater efforts are needed in identifying acute HIV infection in
      STD clinics. This article summarizes a presentation by Myron S. Cohen, MD, at the
      International AIDS Society-USA course in Chicago in May.

PMID- 15516708
TI  - Secrets and safety in the age of AIDS: does HIV disclosure lead to safer sex?
AB  - To fuel the HIV/AIDS epidemic, HIV-seropositive individuals must interact
      unsafely with HIV-seronegative individuals. Research indicates that up to one
      third of individuals diagnosed with HIV continue to have unprotected sex, at
      times without informing partners, who may be of negative or unknown serostatus.
      Some research and public health interventions have focused on encouraging HIV
      positive individuals to reveal their serostatus to their sexual partners,
      predicated upon the assumption that disclosure will increase the safety of
      subsequent sexual activity with informed partners. This review examines the
      empirical literature on disclosure of HIV status and subsequent sexual risk
      behaviors of HIV-positive individuals. Only 15 of the 23 studies reviewed
      provided data that allowed us to examine the association between disclosure and
      safer sex. Fewer still provided a methodologically sound analysis, and those that
      did provided conflicting results, often with significant effects limited to only
      1 subgroup of participants. However, this failure to demonstrate a consistent
      association does not necessarily mean that disclosure is irrelevant to the
      practice of safer sex. We discuss limitations of the research to date and
      implications for policy and practice.

PMID- 15516709
TI  - Update of the drug resistance mutations in HIV-1: 2004.

PMID- 15516711
TI  - Identification of muscle-type carnitine palmitoyltransferase I and
      characterization of its atypical gene structure.
AB  - To characterize energy metabolism in rat brown adipose tissue (BAT), we carried
      out differential screening of a cDNA library of BAT with a cDNA probe of white
      adipose tissue and isolated one novel cDNA clone. It contained a single open
      reading frame of 2316 bases, which encodes a protein of 88.2 kDa. The predicted
      amino acid sequence showed the highest homology (62.6%) with that of carnitine
      palmitoyltransferase I (CPTI) from rat liver. The transcript corresponding to
      this cDNA was found to be abundantly expressed not only in BAT but also in heart
      and skeletal muscle. CPTI is known to be a protein necessary for the beta
      oxidation of long-chain fatty acids in mammalian mitochondria, and it has been
      suggested that at least two isoforms, the liver type and muscle type, exist. From
      these observations, a cDNA clone isolated from rat BAT was concluded to be
      encoding muscle-type CPTI (M-CPTI). Characterization of a genomic DNA clone
      revealed that the gene for human M-CPTI consists of two 5'-noncoding exons, 18
      coding exons, and one 3'-noncoding exon spanning approximately 10 kbp, and a gene
      encoding choline/ethanolamine kinase-beta (CK/EK-beta) was located only about 300
      bp upstream from the M-CPTI gene with the same strand direction. Furthermore, we
      found that unordinary transcripts containing exons of both CK/EK-beta and M-CPTI
      genes exist in human and rodent tissues. Although the physiologic role(s) of
      these transcripts is still unknown, it is interesting that such transcripts are
      produced from two tightly arranged and functionally unrelated genes.

PMID- 15516710
TI  - Mechanisms of action of cognitive enhancers on neuroreceptors.
AB  - No strategies for curing Alzheimer's disease have been developed yet as we do not
      know the exact cause of the disease. The only therapy that is available for
      patients is symptomatic treatment. Since Alzheimer's disease is associated with
      downregulation of the cholinergic system in the brain, its stimulation is
      expected to improve the patients' cognition, learning, and memory. Four
      anticholinesterases have been approved in the U.S.A. for the treatment of
      Alzheimer's disease patients. However, because of the inhibition of
      cholinesterases, these drugs have side effects and their effectiveness does not
      last long. Thus new approaches are needed. One approach is to stimulate directly
      nicotinic acetylcholine (nACh) receptors in the brain, and another is to
      stimulate NMDA receptors which are also known to be downregulated in Alzheimer's
      patients. Nefiracetam has been shown to potentiate ACh currents in the
      alpha4beta2 receptor of rat cortical neurons with a bell-shaped dose-response
      relationship and the maximum effect at 1 nM. This effect was exerted via G(s)
      proteins. The alpha7 receptor was almost unaffected by nefiracetam. Nefiracetam
      also potentiated NMDA currents with the maximum effect at 10 nM via interaction
      with the glycine-binding site of the receptor. Galantamine had a moderate
      potentiating effect on the alpha4beta2 receptor and potentiated NMDA currents
      with the maximum effect at 1 microM. However, galantamine did not interact with
      the glycine-binding site. Donepezil, a potent anticholinesterase, also
      potentiated NMDA currents at 1-10000 nM. In conclusion, these three drugs
      potentiate the activity not only of the cholinergic system but also of the NMDA
      system, thereby stimulating the downregulated nACh receptors and NMDA receptors
      to improve patients' learning, cognition, and memory.

PMID- 15516712
TI  - Mucoadhesive microspheres for controlled drug delivery.
AB  - Mucoadhesion is a topic of current interest in the design of drug delivery
      systems. Mucoadhesive micro-spheres exhibit a prolonged residence time at the
      site of application or absorption and facilitate an intimate contact with the
      underlying absorption surface and thus contribute to improved and/or better
      therapeutic performance of drugs. In recent years such mucoadhesive microspheres
      have been developed for oral, buccal, nasal, ocular, rectal and vaginal routes
      for either systemic or local effects. The objective of this article is review the
      principles underlying the development and evaluation of mucoadhesive microspheres
      and the research work carried out on these systems.

PMID- 15516713
TI  - Chromogenic assay for the activity of sphingomyelinase from Bacillus cereus and
      its application to the enzymatic hydrolysis of lysophospholipids.
AB  - We developed a convenient chromogenic assay method for the activity of
      sphingomyelinase (SMase) from Bacillus cereus. SMase reaction was quenched by
      Zn(2+), and the released phosphocholine was converted into a choline by the
      action of alkaline phosphatase. After that, the choline was converted into a
      chromogenic dye by the actions of choline oxidase and peroxidase in the presence
      of EDTA to trap the added Zn(2+) which could interfere with the choline
      oxidase/peroxidase reactions. Triton X-100 also was added to the reaction
      mixture, in order to remove turbidity generated from ceramide which had been
      produced by the SMase reaction. To test a large number of samples in a short
      period of time, this assay was performed using 96-well microtiter plates. This
      method proved to be applicable not only to the measurement of the hydrolysis of
      sphingomyelin but also to those of lysophosphatidylcholine (lysoPC) and lyso
      platelet-activating factor by B. cereus SMase. Using this method, the kinetic
      parameters (K(m) and k(cat)) for B. cereus SMase toward various types of
      substrates were then determined, and the effect of Triton X-100 on the hydrolysis
      of lysoPC was examined.

PMID- 15516714
TI  - Effects of omeprazole, famotidine, and ranitidine on the enzyme activities of
      carbonic anhydrase from bovine stomach in vitro and rat erythrocytes in vivo.
AB  - In this study, the effects of omeprazole, famotidine, and ranitidine on bovine
      stomach carbonic anhydrase (EC 4.2.1.1.) isoenzymes have been investigated in
      vitro. Bovine stomach carbonic anhydrase (CA) was purified from four different
      cell localisations of bovine stomach using affinity chromatography by Sepharose
      4B-L-tyrosine sulphanilamide. The inhibition or activation effects of three
      different medical drugs on CA isoenzymes were determined using esterase activity
      and the CO(2)-hydratase method by plotting activity % vs. [medical drug]. The
      K(i) values for omeprazole, famotidine, and ranitidine were determined in all
      localization CA, respectively. The I(50) values of the drugs exhibiting an
      inhibition effect were found by means of these graphs. It was observed that
      omeprazole, famotidine, and ranitidine showed inhibition of bovine stomach CA
      activity. In addition, in vivo studies were performed for these medical drugs in
      Sprague-Dawley rats. It was demonstrated that CA in erythrocytes was
      significantly inhibited by these drugs to 3 h.

PMID- 15516715
TI  - Proteome analysis of focal adhesion kinase (FAK)-overexpressing cells.
AB  - We established several focal adhesion kinase (FAK) cDNA-transfected cells and
      found that FAK-transfected HL-60 (HL-60/FAK) cells are resistant to apoptosis
      induced with hydrogen peroxide, etoposide and radiation compared with the
      parental HL-60 or the vector-transfected (HL-60/Vect) cells. We carried out
      proteome analysis to study the mechanism of resistance to apoptosis in HL-60/FAK
      cells. Among 300 spots resolved in two-dimensional gels, ca. 10% of them were
      significantly increased in HL-60/FAK cells compared with HL-60/Vect cells,
      whereas ca. 2% of them were decreased or disappeared. These proteins were
      performed for further analysis by Western blots or N-terminal sequencing or mass
      spectrometry. Increased proteins included stress proteins such as hsp90,
      ribosomal proteins, and antioxidant enzymes such as peroxyredoxin 2. Some of
      these proteins are assumed to contribute to the antiapoptotic action of FAK.

PMID- 15516716
TI  - Identification of the novel membrane-associated protein AgK114 on hamster
      keratinocytes recognized by a monoclonal antibody K114.
AB  - We have established a monoclonal antibody K114 (mAbK114) against hamster
      keratinocytes. The mAbK114 recognizes a 50-95 kDa cell-surface protein that is
      expressed restrictedly in the dermal sheath cells near the bulge area of the hair
      follicle and in the differentiated sebocytes of the normal adult hamster skin.
      Upon being cultured in vitro, however, the keratinocytes strongly and transiently
      expressed this novel K114 antigen (AgK114) in spite of low expression level of
      AgK114 by the freshly prepared keratinocytes. The cDNA of AgK114 was isolated by
      expression cloning using mAbK114. Sequence analysis revealed that it had 242
      amino acid residues with a signal peptide at the N terminus, potential six N
      glycosylation sites, a characteristic repetitive threonine rich domain, and a
      possible glycosylphosphatidylinositol (GPI) anchoring site near the C terminus.
      We examined various conditions in which expression of AgK114 was enhanced in
      vivo. Interestingly, AgK114 molecule was expressed accompanying tissue damages of
      the skin. It was transiently induced in basal epidermal keratinocytes after UV
      exposure. In addition, AgK114 was also induced in elongating edge epidermal
      keratinocytes during tissue regeneration after an excised wounding. These results
      suggest that AgK114 is involved in the recovering process from injury.

PMID- 15516717
TI  - Predominant contribution of IFN-beta expression to apoptosis induction in human
      uterine cervical fibroblast cells by influenza-virus infection.
AB  - We have been investigating an apoptosis induction in human fetal membrane cells
      by influenza virus (IV) infection and the contribution of apoptosis induction to
      the viral infection-defense response between a fetus and the maternal body. For
      studying any role of uterine cells in the anti-viral response, we investigated
      the molecular mechanism of the apoptotic induction in human uterine cervical
      fibroblast cell line (HCF) by IV infection. IV type A and B infection induced DNA
      fragmentation in HCF. In IV-infected HCF, gene mRNA expression levels of
      interleukine (IL)-1beta, IL-6, tumor necrosis factor (TNF) alpha, Fas ligand,
      interferon regulatory factor (IRF)-1, interferon (IFN) alpha and IFN beta
      increased as compared with those in mock treatment cells, and the induction of
      mRNAs for double stranded RNA dependent protein kinase (PKR), indolamine 2,3
      deoxygenase (IDO) and 2'-5' oligoadenylate synthetase (2-5 OAS) were indicated,
      which had a role for a host defense response induced by IFN-beta. The amount of
      IFN-beta protein increased by IV-infection, and DNA fragmentation was inhibited
      with anti-IFN-beta antibody and PKR inhibitor (2-aminopurine). Furthermore, a
      synthetic double stranded RNA, poly I : C, could induce almost the same phenomena
      as that induced by virus infection. We conclude that IV-infection induces the
      apoptosis in HCF cells through the IFN-beta expression regulated by double
      stranded RNA and IRF-1 induction, and suggest that the IFN-beta induction may be
      the predominant contribution to the IV infection induced HCF apoptosis.

PMID- 15516718
TI  - Zonal differences in DNA synthesis and in transglutaminase activity between
      perivenous versus periportal regions of regenerating rat liver.
AB  - We investigated a relationship within zonal differences in DNA synthesis and in
      transglutaminase (TGase) activity between perivenous versus periportal regions of
      regenerating rat liver. Using the digitonin/collagenase perfusion technique,
      hepatocyte subpopulations were isolated from each region at various time points
      after partial hepatectomy. The amounts of DNA synthesis as well as the levels of
      TGase mRNA and activity in each subpopulation were measured. Although increased
      DNA synthesis was observed in both subpopulations with a peak at 24 h after
      partial hepatectomy, the amount of DNA synthesis in periportal hepatocytes (PPH)
      was twice as much as that in perivenous hepatocytes (PVH). In PVH, TGase activity
      peaked at 24 h after partial hepatectomy with a preceding increase in its mRNA
      expression at 12 h, whereas TGase activity in PPH at 24 h was one-half of that in
      PVH. As TGase is known to have a growth-arresting activity, our data indicate
      that relatively higher TGase activity in PVH at 24 h after partial hepatectomy
      might correlate with relatively lower DNA synthesis in this region compared to
      periportal region.

PMID- 15516719
TI  - Characterization of chondroitin/dermatan sulfate proteoglycans synthesized by
      bovine retinal pericytes in culture.
AB  - Pericytes associate with the outside of endothelial cells in microvessels.
      Previous studies have shown that these cells synthesize glycosaminoglycans (GAGs)
      but the nature of the core proteins to which these GAGs are attached is unknown.
      In the present study, cultured bovine retinal pericytes were metabolically
      labeled with [(3)H]glucosamine, [(35)S]sodium sulfate or (35)S-labeled amino
      acids and the proteoglycans synthesized by these cells were purified by DEAE
      Sephacel ion exchange and molecular sieve Sepharose CL-4B chromatography.
      Separated proteoglycans were digested with papain, heparitinase or chondroitin
      ABC lyase and the GAGs characterized by Sepharose CL-6B chromatography.
      Proteoglycans were also assessed by sodium dodecyl sulfate polyacrylamide gel
      electrophoresis before and after digestion with chondroitin ABC lyase. Pericytes
      predominantly synthesize and secrete chondroitin or dermatan sulfate
      proteoglycans (CS/DS PGs) rather than heparan sulfate proteoglycans (HSPGs). Two
      subclasses of CS/DS PGs are synthesized by pericytes; one is a high M(r) subclass
      with high charge density. This subclass eluted at the void volume of a Sepharose
      CL-4B molecular sieve column, was susceptible to chondroitin ABC lyase, and
      contained core proteins of ca. 550 and 450 kD which were recognized by antibody
      to versican. The other major subclass eluted at a K(av) ca. 0.45 on a Sepharose
      CL-4B molecular sieve column, was susceptible to chondroitin ABC lyase, and
      contained core proteins recognized by antibodies to either biglycan or decorin
      that separated as a broad band of ca. 50 kDa in SDS-PAGE. A small amount of HSPG
      was also synthesized by these cells and could be separated from the CS/DS PGs by
      DEAE-Sephacel chromatography using a linear gradient of 0.1-0.7 M NaCl. Release
      of GAG chains by protease digestion indicated that the length of GAG chains was
      approximately M(r) 45000 in biglycan and decorin, approximately M(r) 48000 in the
      small amount of HSPGs and approximately M(r) 66000 in versican. These
      proteoglycans resemble those synthesized by vascular smooth muscle cells but
      differ markedly from those synthesized by vascular endothelial cells.

PMID- 15516720
TI  - Gambogic acid inhibits proliferation of human lung carcinoma SPC-A1 cells in vivo
      and in vitro and represses telomerase activity and telomerase reverse
      transcriptase mRNA expression in the cells.
AB  - We determined the in vivo and in vitro antitumor activities of gambogic acid (GA)
      and one of the possible mechanisms for its inhibitory activities. In vivo
      antitumor activity of GA was evaluated by the relative tumor growth ratio (T/C)
      in nude mice, and in vitro inhibition of SPC-A1 cells was measured by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and trypan
      blue exclusion assay. Telomere repeats amplification protocol (TRAP)-polymerase
      chain reaction (PCR)-enzyme-linked immunosorbent assay (ELISA) and RT-PCR were
      used to quantitatively detect telomerase activity and the expression of human
      telomerase reverse transcriptase (hTERT) mRNA, respectively. Results from our in
      vivo study showed that transplantable tumor growth remained suppressed for up to
      21 d with minimal animal weight loss in nude mice treated with gambogic acid
      (i.v.). Proliferation of SPC-A1 cells cultured in vitro was significantly
      inhibited (p<0.01), showing time-dependent and dose-dependent inhibition.
      Telomerase activity and hTERT mRNA expression were both decreased significantly,
      when cells were exposed to gambogic acid for 24, 48 and 72 h (for 24 h p<0.05,
      and for 48, 72 h, p<0.01). These results suggeste that gambogic acid could
      inhibit the growth of SPC-A1 cells and its tumor xenografts, and when treated
      with gambogic acid for a period of time, telomerase activity and expression of
      hTERT mRNA in the tumor cells were both inhibited significantly. It is safe, at
      least in part, to conclude that the down-regulating telomerase activity of GA by
      modifying partly the expression of hTERT mRNA in SPC-A1 cells may be one possible
      mechanism for the inhibitory activity of GA in the cells.

PMID- 15516721
TI  - Licorice flavonoids suppress abdominal fat accumulation and increase in blood
      glucose level in obese diabetic KK-A(y) mice.
AB  - Licorice, the root of the Glycyrrhiza species, is one of the most frequently
      employed botanicals in traditional medicines. In this study, we investigated the
      effects of hydrophobic flavonoids from Glycyrrhiza glabra LINNE on abdominal fat
      accumulation and blood glucose level in obese diabetic KK-A(y) mice. In order to
      enrich a fraction of hydrophobic flavonoids, licorice flavonoid oil (LFO) was
      prepared by further extracting licorice ethanolic extract with medium-chain
      triglycerides (MCT), and adjusting the concentration of glabridin, the major
      flavonoid of licorice, to 1.2% in oil. KK-A(y) mice aged 6 weeks were assigned to
      5 groups (n=6 each), and fed a high-fat diet containing 0 (control), 0.5%, 1%, or
      2% LFO, or 0.5% conjugated linoleic acid (CLA) for 4 weeks. Compared with the
      control, body weight gain and weights of abdominal adipose tissues were
      suppressed (p<0.05) by feeding the diet containing 2% LFO, and blood glucose
      levels after 2 and 4 weeks were suppressed by all of the diets containing LFO.
      Although CLA feeding suppressed (p<0.05) body weight gain, it increased (p<0.05)
      blood glucose level after 2 weeks compared with the control level. Furthermore,
      LFO and licorice ethanolic extract stimulated human adipocyte differentiation in
      vitro. These results indicate that licorice hydrophobic flavonoids have abdominal
      fat-lowering and hypoglycemic effects, possibly mediated via activation of
      peroxisome proliferator-activated receptor-gamma (PPAR-gamma).

PMID- 15516722
TI  - Effects of morin on blood pressure and metabolic changes in fructose-induced
      hypertensive rats.
AB  - High fructose (HF) feeding induces a moderate increase in blood pressure in rats,
      which is associated with insulin resistance, hyperinsulinemia, and
      hypertriglyceridemia. In the present study, we examined the chronic effect of
      morin, a flavonoid isolated from medicinal plants, on blood pressure, lipid
      profiles, and serum insulin and glucose in HF-induced hypertensive rats. Rats
      were divided into control group and HF-fed group during the first three weeks of
      experiments. Then, rats were further divided into four groups and treated for 4
      more weeks as follows: 1) control group; 2) morin-treated (intraperitoneal 5
      mg/kg/d) control group; 3) HF-fed group; 4) morin-treated, HF-fed group (n=8,
      each group). Morin-treated HF-fed group showed lower systolic blood pressure
      (SBP) (132.0+/-2.5 mmHg vs. 142.8+/-2.2 mmHg, p<0.05), lower serum insulin level
      (1.21+/-0.27 vs. 2.73+/-0.30 microIU/dl, p<0.05), and lower plasma triglycerides
      (47.8+/-5.0 vs. 65.5+/-5.0 mg/dl, p<0.05) than those of HF-fed group. Morin
      treatment also suppressed mRNA expression of endothelin-1 (ET-1) in the thoracic
      aorta from HF-induced hypertensive rats. Moreover, decreased renal sodium
      excretion in HF-induced hypertensive rats was ameliorated by morin treatment. In
      conclusion, the results of this study demonstrate that morin has an anti
      hypertensive effect in HF-induced hypertensive rats. This effect of morin may be
      associated with the suppression of serum insulin and plasma triglyceride level,
      with the down-regulation of ET-1 in the thoracic aorta, and with the partial
      amelioration of renal dysfunctions in HF-induced hypertensive rats.

PMID- 15516723
TI  - Difference between deep seawater and surface seawater in the preventive effect of
      atherosclerosis.
AB  - Using surface and deep seawater collected in the sea area of Muroto Cape (Kochi,
      Japan), desalinated drinking samples of about 1200 hardness were prepared and
      examined for the effects on the prevention of atherosclerosis in dietary induced
      hyperlipidemia rabbits. The plasma LDL cholesterol level was lower in the deep
      seawater group than in the surface seawater group. GPx activity was significantly
      higher in the deep seawater group than in the control group, while there was no
      difference between the surface seawater and control groups. The level of LPO was
      also significantly lower in the deep seawater group than in the control group.
      The Sudan IV lipid stained area ratio on the inner surface of the aorta was
      significantly lower in the deep seawater groups than in the control group, while
      there was no difference between the surface seawater and control groups. The oil
      red O stained cross section of the aorta in the control and surface seawater
      administration group foam cells had accumulated to form thick layers, while in
      the deep seawater administration group, the degree of their accumulation was very
      low. These results suggested that the deep seawater was useful for the prevention
      of hyperlipidemia and arteriosclerosis compared to the surface seawater, and it
      was found that reduction of the LDL cholesterol level and enhancement of GPx
      activity were involved in its effects.

PMID- 15516724
TI  - Protective effect of DY-9760e, a calmodulin antagonist, against neuronal cell
      death.
AB  - An excessive elevation of intracellular Ca(2+) levels is known to play a key role
      in the pathological events following cerebral ischemia. DY-9760e, 3-[2-[4-(3
      chloro-2-methylphenylmethyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4
      imidazolylmethyl)-1H-indazole dihydrochloride 3.5 hydrate, is a potent calmodulin
      antagonist that attenuates brain damage in focal ischemia models. In the present
      study, we investigated the effect of DY-9760e on neuronal cell death induced by a
      variety of cell-toxic stimuli that increase intracellular Ca(2+). Cell death was
      induced by the exposure of primary cultured neurons to excitotoxic agents such as
      glutamate and N-methyl-D-aspartate, membrane-depolarizing agents such as
      veratridine and high KCl, or thapsigargin an endoplasmic reticulum Ca(2+)-ATPase
      inhibitor. Treatment with DY-9760e resulted in a dose-dependent prevention of
      neuronal cell death elicited by excitotoxicity, voltage-gated channel opening,
      and inhibition of endoplasmic reticulum Ca(2+)-ATPase. These results indicate
      that DY-9760e can rescue neurons from various types of cell-toxic stimuli, which
      may contribute to attenuation of brain injury after cerebral ischemia.

PMID- 15516725
TI  - Effect of taurine on biliary excretion and metabolism of acetaminophen in male
      hamsters.
AB  - The effect of taurine intake on the biliary disposition and toxicity of
      acetaminophen (APAP) was examined in male Golden-Syrian hamsters. Animals were
      provided with taurine (5 mM) in drinking water for 1 week followed by APAP
      treatment (250 mg/kg, i.p.). Biliary excretion and plasma concentrations of APAP
      and its major metabolites were determined for up to 360 min. Taurine increased
      the bile flow, whereas the concentration of APAP or the metabolites in bile was
      not altered significantly. Accordingly the total biliary excretion of APAP and
      the metabolites was increased in hamsters fed taurine. Taurine increased the
      plasma concentrations of APAP-glutathione (GSH) and APAP-mercapturate, but the
      APAP-glucuronide or APAP-sulfate concentration was not changed. The area under
      the curve of the plasma APAP concentration was reduced significantly, suggesting
      that the elimination of APAP was enhanced by taurine intake. However, the
      hepatotoxicity resulting from a dose of APAP (450 mg/kg, i.p.) was not altered by
      taurine intake as determined by the elevation of serum alanine aminotransferase,
      aspartate aminotransferase, and sorbitol dehydrogenase activities. The results
      suggest that taurine administration could affect the disposition of APAP by
      enhancing its metabolism through the GSH-dependent pathway and also by increasing
      the biliary excretion of this drug and its metabolites. The pharmacological
      significance of this finding remains to be examined.

PMID- 15516726
TI  - Strong antihyperglycemic effects of water-soluble fraction of Brazilian propolis
      and its bioactive constituent, 3,4,5-tri-O-caffeoylquinic acid.
AB  - To clarify the suppression of postprandial blood glucose rise via alpha
      glucosidase (AGH) inhibitory action by natural compounds, propolis was examined
      in this study. A single oral administration of propolis extract (50% methanol
      fraction on XAD-2 column chromatography) in Sprague-Dawley rats demonstrated a
      potent antihyperglycemic effect with the significant AUC(0-120 min) reduction of
      38% at a dose of 20 mg/kg compared to that of controls. Among the active
      compounds isolated from the fraction, 3,4,5-tri-caffeoylquinic acid was found to
      be a prominent candidate that exerts the effect and shows a strong maltase
      specific inhibition with an IC(50) value of 24 microM. In addition, the
      noncompetitive inhibition power apparently increased with the number of caffeoyl
      groups bound to quinic acid.

PMID- 15516727
TI  - Isolation of the acetylcholinesterase inhibitor ungeremine from Nerine bowdenii
      by preparative HPLC coupled on-line to a flow assay system.
AB  - In an attempt to isolate the active compound while detecting acetylcholinesterase
      inhibitory activity, we applied a fluorometric flow assay system to an on-line
      coupled preparative HPLC. The MeOH extract of Nerine bowdenii showed a strong
      inhibitory peak in the on-line assay, and the active compound was isolated by CPC
      and HPLC. It was identified as ungeremine by analysis of its (1)H-NMR, 2D-NMR,
      and NOESY spectra. The assignment of the active N. bowdenii constituent was also
      confirmed by co-TLC, co-HPLC, and co-(1)H-NMR experiments using an authentic
      sample of synthetic ungeremine. The IC(50) value of ungeremine was 0.35 microM,
      showing stronger activity than galanthamine (2.2 microM).

PMID- 15516728
TI  - Inhibitory effect of Chunghyuldan in prostaglandin E2 and nitric oxide
      biosynthesis of lipopolysaccharide-induced RAW 264.7 cells.
AB  - Chunghyuldan (Daio-Orengedokuto in Japanese) (CHD) has been used as an
      antihyperlipidemic and antiischemic agent in Korea. To evaluate in vitro the
      efficacy of Chunghyuldans (CHDs) metabolized with and without human intestinal
      microflora against brain ischemia, we investigated its anti-inflammatory effect
      on LPS-induced RAW264.7 cells. Both metabolized CHD (MCHD) and CHD showed
      antioxidant activities in vitro, and inhibited nitric oxide (NO) and
      prostaglandin E2 (PGE2) productions in lipopolysaccharide (LPS)-induced RAW264.7
      cells. These also inhibited enzyme activities and protein expressions of
      inducible NO synthase and cyclooxygenase-2 in LPS-induced RAW264.7 cells. MCHD
      inhibitory activity against NO and PGE2 productions in LPS-induced RAW264.7 cells
      was more potent than those of CHD. These results suggest that CHD may show potent
      anti-inflammatory activity in vivo and can improve brain ischemia.

PMID- 15516729
TI  - Chemical composition and in vitro antimicrobial activities of the essential oils
      from endemic Psiadia species growing in mauritius.
AB  - The composition of the leaf oils, obtained by hydrodistillation, of five endemic
      Psiadia species of the Asteraceae family were studied by GC/MS on both polar and
      non-polar columns. The analysis showed that the volatile components of the oils
      were made up essentially of monoterpenes, sesquiterpenes, aliphatics and other
      shikimic acid derivatives. With respect to the non-volatile components, great
      variations were observed: P. lithospermifolia contained (E)-isoasarone (51.5%);
      P. penninervia: eugenol (5.1%); P. terebinthina: eugenyl-acetate (4.0%); P.
      viscosa: pentyl-4-(1-methylethyl benzoate) (25.8%); P. arguta: isoeugenol
      (56.5%). In vitro antimicrobial assays using the agar-well diffusion method,
      revealed that most of the oils were not very active against the tested
      microorganisms except for that of P. lithospermifolia, which significantly
      inhibited the growth of Bacillus cereus, Staphylococcus aureus and Pseudomonas
      aureofaciens, Aspergillus ochraceus, Candida pseudotropicalis, Kluyveromyces
      lactis and Fusarium moniliforme. This activity has been attributed to the
      presence of delta-elemene, (E)-farnesene, alpha-curcumene, selina-4,7(11)-diene,
      (E,Z)-alpha-farnesene, beta-bisabolene some of which have established
      antimicrobial profiles. Likewise, the fungi toxic action of the oil of P. arguta
      against Aspergillus ochraceus, Candida pseudotropicalis, and Fusarium
      moniliforme, may be attributed to the presence of isoeugenol, eugenol being known
      to be mycotoxic especially against Aspergillus species.

PMID- 15516730
TI  - Essential oils from sweet basil (Ocimum basilicum) as novel enhancers to
      accelerate transdermal drug delivery.
AB  - The purpose of this study was to evaluate the essential oils from sweet basil
      (Ocimum basilicum, OB) as skin permeation enhancers to promote the percutaneous
      absorption of drugs. The in vitro and in vivo irritancy of the essential oils was
      also examined. Terpenes with various carbon numbers (mono-, sesqui-, di-, and tri
      ) were identified in both the lower-polarity fraction (OB-1) and higher-polarity
      fraction (OB-2). In vitro skin permeation and deposition of indomethacin were
      significantly enhanced after treatment with OB essential oils. The enhancing
      effect of OB-1 was greater than that of OB-2 in the in vitro permeation and in
      vivo cutaneous microdialysis analyses as well as in the plasma concentration of
      indomethacin. On the other hand, the in vivo study showed that OB-2 had a greater
      ability to retain the drug within the skin than did OB-1. Enhancement of the skin
      permeation of drugs by OB essential oils might be mainly due to improvement in
      the partitioning of the drugs to the stratum corneum. Both in vitro cell cultures
      (keratinocytes and skin fibroblasts) and in vivo transepidermal water loss showed
      no or only negligible irritation to skin by OB essential oils.

PMID- 15516731
TI  - Functional characterization of the carrier-mediated transport system for glycerol
      in everted sacs of the rat small intestine.
AB  - The mechanism of intestinal glycerol transport was investigated by using the in
      vitro everted sac method involving the rat small intestine. The uptake of
      glycerol into everted sacs was saturable with a Michaelis constant (K(m)) of 0.77
      mM and a maximum transport rate (J(max)) of 11.5 nmol/min/100 mg wet tissue
      weight (wtw), suggesting the involvement of carrier-mediated transport, and was
      accompanied by unsaturable transport (passive transport) with a membrane
      permeability clearance (CL(m,d)) of 4.9 microl/min/100 mg wtw. The carrier
      mediated uptake of glycerol was inhibited by the removal of Na(+) and also by the
      addition of 2,4-dinitrophenol (DNP) and sodium azide (NaN(3)), which are
      metabolic inhibitors. These results suggest that the carrier-mediated glycerol
      transport is Na(+)-dependent and secondary active. Since glycerol uptake was also
      inhibited by p-chloromercuribenzene sulfonate (pCMBS), a thiol-modifying reagent,
      cysteine residues, which have a thiol group, seem to play an important role in
      the function of the carrier. We further found that glycerol uptake was
      selectively inhibited by glycerol-3-phosphate, chloramphenicol and voglibose,
      which are alcohol-related compounds analogous to glycerol. Several other
      compounds that did not inhibit glycerol uptake included D-glucose and 5
      fluorouracil, which are known to be transported by specific carriers, and none of
      the selective inhibitors of glycerol uptake inhibited the uptake of D-glucose and
      5-fluorouracil. Therefore, the carriers for these two compounds do not seem to be
      involved in glycerol uptake. It is likely that the carrier-mediated transport
      system involved in glycerol uptake is specific to glycerol and, possibly, some
      analogous compounds with hydroxyl groups. It would be interesting to examine the
      possibility that the carrier-mediated glycerol transport system might be involved
      in drug absorption and also that it might be used for oral drug delivery.

PMID- 15516732
TI  - Impact of a pharmacist-implemented anemia management in outpatients with end
      stage renal disease in Japan.
AB  - Given the absence of standard guidelines for use of recombinant human
      erythropoietin in patients with end-stage renal disease in Japan, in the present
      study, pharmacists actively managed the erythropoietin therapy, and the
      therapeutic and pharmacoeconomic outcome was evaluated. We compiled in-hospital
      guidelines for proper use of erythropoietin for outpatients with renal anemia
      under hemodialysis, and made recommendations, particularly about changes in the
      doses of erythropoietin and administration of iron preparations, to physicians.
      The clinical test values and the dosages of erythropoietin were monitored for 9
      months and analyzed. As results of our participation, the number of renal anemia
      patients with over 30% of the hematocrit value as a therapeutic target increased
      from 7 to 32 among 41 patients. Twenty three of the 41 patients could decrease
      the dose of erythropoietin, and 5 patients could cease receiving the drug.
      Monthly total units of erythropoietin used for the 41 patients could also be
      decreased from 915000 units to 642000 units, resulting in considerable
      improvement of cost performance. Thus, active participation of pharmacists in
      management of renal anemia had great therapeutic and pharmacoecomic impact in
      Japan, as in North America.

PMID- 15516733
TI  - Comparative evaluation of in-vitro effects of Brazilian green propolis and
      Baccharis dracunculifolia extracts on cariogenic factors of Streptococcus mutans.
AB  - Streptococcus mutans triggers dental caries establishment by two major factors:
      synthesis of organic acids, which demineralize dental enamel, and synthesis of
      glucans, which mediate the attachment of bacteria to the tooth surface. Propolis
      is a natural product that may prevent dental caries. Baccharis dracunculifolia DC
      (Asteraceae), a native plant from Brazil, is the most important botanical origin
      for the production of green propolis (Brazilian propolis) by honeybees. However,
      whether B. dracunculifolia (Bd) has an anticariogenic effect, like green
      propolis, remains unknown. Herein, we have made a comparative evaluation of the
      effects of extracts from green propolis and Bd on the glucan synthesis and
      acidogenic potential of S. mutans. The inhibitory effects of the extracts on
      bacterial acid production were evaluated through the potentiometric measurement
      of pH from bacterial suspensions treated with serial concentrations of both
      extracts. Besides presenting close inhibitory values at the same concentration
      range, Bd leaf rinse and green propolis extracts had similar IC(50) values (0.41
      and 0.34 mg/ml, respectively). Both extracts produced a bacteriostatic effect on
      S. mutans cultures at a concentration of 0.40 mg/ml. Estimated inhibitory values
      of green propolis and Bd leaf rinse extracts on the synthesis of insoluble
      glucans (IC(50)=12.9 and 25.0 microg/ml, respectively) and soluble glucans
      (IC(50)=50.4 and 49.1 microg/ml, respectively) were not significantly different
      from each other at p<0.05. The results demonstrate that Bd leaf rinse and green
      propolis extracts have similar inhibitory effects on the S. mutans cariogenic
      factors evaluated herein, and allowed us to suggest that Bd leaves may be a
      potential source for pharmaceutical products employed for this purpose.

PMID- 15516734
TI  - Limitation of polymyxin B on suppression of endotoxin shock induced by Salmonella
      infection in mice.
AB  - The protective effects of an antibiotic polymyxin B (PLB), having
      lipopolysaccharide (LPS)-binding activity, on infection-induced endotoxin shock
      in mice were investigated. Infection with 10(8) colony forming units of an
      attenuated Salmonella typhimurium aroA strain caused lethal endotoxin shock to
      ddY mice. Treatment with PLB 1 h post infection (p.i.) resulted in significant
      reduction of mortality and bacterial numbers in livers. In addition, treatment
      with PLB 1 h p.i. resulted in a transient increase at the early stage and gradual
      decline in plasma LPS levels. Although plasma levels of sCD14 and high mobility
      group box chromosomal protein-1 (HMGB-1) increased according with progression of
      infection, increases in plasma levels of sCD14 and HMGB-1 were downregulated by
      treatment with PLB 1 h p.i. However, the lethal shock was not blocked by
      treatment with anti-CD14 monoclonal antibody at 3 h and 6 h p.i. Interestingly,
      administration of PLB 6 h p.i. did not show any protective activities, indicating
      that a time window for effective PLB action is present.

PMID- 15516735
TI  - Studies on the interactions between drugs and estrogen. III. Inhibitory effects
      of 29 drugs reported to induce gynecomastia on the glucuronidation of estradiol.
AB  - To determine the inhibition effects of drugs on the glucuronidation of estradiol
      (E2), 29 drugs that have been reported to induce gynecomastia were examined in
      the presence of UDP-glucuronic acid using human hepatic microsomes (pooled) as
      the enzyme source. The percentage inhibition of the E2 glucuronidation was
      determined at drug concentrations of 1 microM (approximate therapeutic
      concentration) and 100 microM (non-clinical overdose concentration) based on the
      rate constants for the 3- and 17-glucuronidation of E2 (11.2 and 2.52 pmol/min/mg
      protein, respectively). The only drug that exhibited 50% or higher inhibition of
      the 3-glucuronidation at a concentration of 1 microM was manidipine (54.4%). When
      the concentration was 100 microM, manidipine exhibited 100% inhibition of the 3
      glucuronidation, and other drugs that exhibited 50% or higher inhibition of the 3
      glucuronidation were nicardipine (92%), nisoldipine (90%), nifedipine (84%),
      domperidone (81%), tacrolimus (80%), nitrendipine (77%) and ketoconazole (69%).
      Conversely, ipriflavone accelerated the formation of estradiol 3-glucuronide in
      the activity of 165% at the concentration of 100 microM. On the 17
      glucuronidation, all of the drugs showed less than 50% inhibition at the
      concentration of 1 microM, but at the concentration of 100 microM, drugs that
      exhibited 50% or higher inhibition consisted of manidipine (79%), chlormadinone
      acetate (74%), nisoldipine (66%), nitrendipine (60%) and ketoconazole (55%).
      Although IC(50) values of these drugs were all lower than the K(m) value (285
      microM) for the 3-glucuronidation of E2, they were higher than the K(m) value for
      the 17-glucuronidation (18.8 microM). Thus, the effect of the drugs on the E2
      glucuronidation should be greater for hydroxy group at the C-3 than that at the C
      17 of E2 molecule. On the other hand, metabolic clearances (V(max)/K(m)) of the 3
      and 17-glucuronidation were about 1/14th and 1/18th of that of the 2
      hydroxylation of E2, respectively. The result implies that, when the contribution
      of the glucuronidation to enterohepatic circulation is taken into consideration,
      the effect of this metabolic inhibition in the estrogen pool cannot be ignored.

PMID- 15516736
TI  - Molecular authentication of the animal crude drug Sailonggu (bone of Myospalax
      baileyi).
AB  - Two pairs of allele-specific diagnostic primers (SL1L/SL1H and SL2L/SL2H) for
      distinguishing the Chinese crude drug Sailonggu (bone of plateau zokor, Myospalax
      baileyi) from its substitutes were designed based on complete sequences of
      mitochondrial 12S rRNA and cytochrome b genes of the original animals of
      Myospalacinae, bamboo rat Rhizomys sinensis and black lipped pika Ochotona
      curzoniae. Total DNA was extracted from crude drug samples and original animals.
      Allele-specific diagnostic PCRs were performed using these primers with the total
      DNA as a template annealing at 65 degrees C. Positive amplifications were
      obtained from all DNA templates of Sailonggu and M. baileyi, whereas negative
      amplifications resulted from those of other zokors, the bamboo rat and black
      lipped pika. These results indicate that Sailonggu samples can be definitely
      distinguished from their substitutes by diagnostic PCR, and no incorrect
      discrimination was found under the same reaction conditions. Each of the two
      diagnostic primer pairs can be used to distinguish crude drug Sailonggu from its
      substitutes or adulterants. The three Sailonggu samples studied were diagnosed as
      genuine Sailonggu. In addition, the results of sequence alignment and
      phylogenetic analysis are congruent with that of the allele-specific diagnostic
      PCR.

PMID- 15516737
TI  - Effect of orthovanadate on platelet aggregation induced by platelet-activating
      factor.
AB  - Orthovanadate (vanadate) inhibited the platelet aggregation induced by platelet
      activating factor (PAF) in a dose-dependent manner. Propranolol, a nonspecific
      beta-adrenergic receptor antagonist, and H-8, a selective inhibitor of cAMP
      dependent protein kinase (PKA), suppressed the inhibition of the PAF-induced
      platelet aggregation by vanadate. Vanadate increased the cAMP content in
      platelets accompanied by the activation of PKA. The beta-adrenergic receptors of
      platelets have been reported to be abundant in the beta(2) isoform, coupled to
      adenylyl cyclases (R. Kerry and M. C. Scrutton, Br. J. Pharmacol., 79, 681-691
      (1983)). When the washed platelets were preincubated with vanadate, salbutamol, a
      selective beta(2)-adrenergic receptor agonist, or 8-Br-cAMP, the latter two
      mimicked the vanadate-induced anti-platelet aggregation and prolongation of
      clotting time of plasma, suggesting involvement of the increased intracellular
      cAMP content in both actions of vanadate. Butoxamine, a selective beta(2)
      adrenergic receptor antagonist, suppressed both actions of vanadate. The vanadate
      induced increase in cAMP content was inhibited in part by butoxamine or
      genistein. These results suggest that vanadate inhibits the PAF-induced platelet
      aggregation by the stimulation of a cAMP/PKA-dependent process via the beta(2)
      adrenergic receptor and receptor tyrosine kinases, and that the anti-platelet
      aggregation is involved in part in mechanisms of the anticoagulant action of
      vanadate.

PMID- 15516738
TI  - Isolated small rat hepatocytes express both annexin III and terminal
      differentiated hepatocyte markers, tyrosine aminotransferase and tryptophan
      oxygenase, at the mRNA level.
AB  - We recently showed that annexin III is expressed in isolated small rat
      hepatocytes but, not in parenchymal hepatocytes. In the present study, we used
      reverse transcription polymerase chain analysis to examine the annexin III mRNA
      level in isolated small rat hepatocytes and parenchymal hepatocytes. Annexin III
      mRNA was detected in isolated small hepatocytes, but not in isolated parenchymal
      hepatocytes, confirming the presence of annexin III expression in isolated small
      rat hepatocytes at the mRNA level and indicating that the absence of annexin III
      expression in isolated parenchymal hepatocytes is due to the absence of annexin
      III mRNA. Furthermore, we examined the mRNA level of tyrosine aminotransferase
      and tryptophan oxygenase, two terminally differentiated hepatocyte markers. mRNA
      for these markers was detected in both parenchymal hepatocytes and small
      hepatocytes.

PMID- 15516739
TI  - Cloning and characterization of testis-specific spermatogenesis associated gene
      homologous to human SPATA4 in rat.
AB  - Rat SPATA4 gene, homologue to the human and mouse SPATA4 gene, expressed
      specifically in the rat testis was cloned by informatics analysis. The cDNA
      mapped to chromosome 16 in the rat genome is made up of 6 exons and the exon
      intron boundaries obey to the AG/GT rule. The gene contains a 972 bp open reading
      frame encoding 323 amino acid sequences with theoretical molecular weight of
      36.64 KD and isoelectric point of 9.65. One CpG island is located in the gene
      from site -200 to +198. A typical promoter is also predicted from site -630 to
      +101. According to the computer-aided analysis of the putative protein encoded by
      the rat SPATA4, no transmembrane region and no signal peptides are found in the
      protein. Multi-tissue RT-PCR results show that the SPATA4 gene is expressed
      specifically in the testis only. Moreover, the expression of SPATA4 occurs in a
      development stage-dependent pattern. According to the RT-PCR results, no
      expression of SPATA4 is detected until the rat is 30 d old after birth. The
      amount of SPATA4 mRNA increases from 30-d to 65-d-old rat and then keeps stable
      after that. In conclusion, this study proves the conservation of SPATA4 in
      mammalian animals and predicts its important role in spermatogenesis.

PMID- 15516741
TI  - Dai-kenchu-to raises levels of calcitonin gene-related peptide and substance P in
      human plasma.
AB  - Sensory afferent neurons in the gastrointestinal mucosa regulate neuropeptides
      [calcitonin gene-related peptide (CGRP), substance P, etc.], which play various
      physiologic roles and are gastroprotective. To determine whether the
      pharmacologic effects of Dai-kenchu-to (DKCT) on the gastrointestine are due to
      changes in gastrointestinal mucosa regulatory peptide levels, we examined the
      effects of the DKCT on the levels of CGRP-like immunoreactive substances (IS) and
      substance P-IS in plasma taken from five healthy subjects. A single oral
      administration of DKCT 7.5 g caused significant increases in plasma CGRP-IS at 40
      min, and in substance P-IS levels at 20 and 60 min, compared with a placebo
      group. The present study may indicate that the pharmacologic action of DKCT is
      closely related to changes in CGRP- and substance P-IS levels.

PMID- 15516740
TI  - OK205 regulates production of inflammatory cytokines in HMC-1 cells.
AB  - OK205 is a traditional Korean prescription containing water-soluble chitosan,
      glucosamine HCl, chondroitin sulfate, and extract of herbal medicine, and has
      been used commercially to treat rheumatoid arthritis (RA). Because infiltrated
      mast cells and their mediators may contribute to the initiation and progression
      of the inflammatory process and matrix degradation of RA, we tested the
      inhibitory effects of OK205 on cytokine production in a human mast cell line (HMC
      1 cells). Production of tumor necrosis factor-alpha was significantly decreased
      to 0.091+/-0.010 ng/ml after treatment of HMC-1 cells with OK205 100 microg/ml.
      The inhibition rate was about 43.57%. In addition, production of interleukin-6 in
      OK205 1 pg/ml-treated cells was 2.779+/-0.071 ng/ml, and the inhibition rate was
      about 50.22%. However, OK205 did not significantly inhibit the production of
      interleukin-8. These findings may help in understanding the mechanism of action
      of OK205, leading to control of mast cells in inflammatory conditions like RA.

PMID- 15516742
TI  - Synthesis and biochemical properties of 6-bromoandrostenedione derivatives with a
      2,2-dimethyl or 2-methyl group as aromatase inhibitors.
AB  - To gain insight into the mechanism for irreversible inactivation of aromatase by
      6beta-bromoandrostenedione (1), one of the earliest discovered suicide
      substrates, in relation to the catalytic function of the enzyme, the 2,2-dimethyl
      derivative of compound 1, steroid 4, and its 6alpha-isomer 5, as well as 2-methyl
      1,4-diene steroid 8 and its 6alpha-bromide 10, were synthesized. All of the
      steroids inhibited aromatase activity in human placental microsomes with apparent
      K(i)'s ranging between 10 and 81 nM. The 2,2-dimethyl-6beta- and 6alpha-bromo
      steroids 4 and 5 were extremely powerful inhibitors (K(i): 14 and 10 nM,
      respectively), but these two did not cause a time-dependent inactivation of
      aromatase in the presence of NADPH; in contrast, the 2-methyl-1,4-diene steroids
      8 and 10 caused time-dependent inactivation with apparent k(inact) of 0.035 and
      0.071 min(-1), respectively, in a suicide manner. These results indicate that the
      2,2-dimethyl function of the 6beta-bromide 4 would prevent the inactivation of
      aromatase caused by inhibitor 1 in a suicide manner, probably through steric
      activity, whereas the 2-methyl group of steroid 8 did not significantly affect
      the suicidal inactivation by the parent 1,4-diene steroid, a typical suicide
      substrate.

PMID- 15516743
TI  - Anti-complementary activity of triterpenoides from fruits of Zizyphus jujuba.
AB  - In order to determine on the anti-complement activity of triterpenes, following
      eleven triterpenoides were isolated from the fruits of the Zizyphus jujuba MILL:
      ceanothane-type triterpenes: colubrinic acid (1), zizyberenalic acid (11); lupane
      type triterpenes: alphitolic acid (2), 3-O-cis-p-coumaroyl alphitolic acid (3), 3
      O-trans-p-coumaroyl alphitolic acid (4), betulinic acid (7), betulonic acid (9);
      and oleanane-type triterpenes: 3-O-cis-p-coumaroyl maslinic acid (5), 3-O-trans-p
      coumaroyl maslinic acid (6), oleanolic acid (8), oleanonic acid (10). These
      compounds were examined for their anti-complement activity against the classical
      pathway of the complement system. Among them, compounds 5, 6, and 8 exhibited
      significant anti-complement activity with IC(50) values of 101.4, 143.9, and
      163.4 microM, respectively, whereas the ceanothane-type and the lupane-type
      triterpenes were inactive. This suggests that the oleanane-structure plays an
      important role in inhibiting the hemolytic activity of human serum against
      erythrocytes.

PMID- 15516745
TI  - Influence of the homogenisation procedure on the physicochemical properties of
      PLGA nanoparticles.
AB  - Pilocarpine HCl-loaded PLGA nanoparticles were prepared by emulsification solvent
      evaporation. Three different stabilisers, polyvinylalcohol (PVA), Carbopol and
      Poloxamer were used, as well as mixtures thereof. The influence of the
      homogenisation pressure and number of cycles on the properties of nanoparticles
      were studied. Particle size was shown to depend on the stabiliser used. An
      increase of the homogenisation pressure or the number of cycles resulted in a
      decrease in particle size. The zeta potential value was influenced mainly by the
      nature of the stabiliser. Particles stabilised with poloxamer or PVA showed a
      slightly negative zeta potential value, while samples stabilised with carbopol
      possessed a more negative zeta potential, which became less negative after
      homogenisation. Drug encapsulation depended strongly on the stabiliser used. The
      higher drug entrapment of the carbopol-stabilised particles could be explained by
      an electrostatic interaction between the negatively charged carboxyl groups of
      carbopol and the positively charged, protonated pilocarpine. The drug release
      patterns of the particles prepared were quite similar. Differences between the
      release patterns of the homogenised particles could be attributed both to
      differences in size as well as drug encapsulation. Turbidimetric measurements
      suggested an interaction between mucin and PLGA nanoparticles exclusively
      stabilised with Carbopol.

PMID- 15516744
TI  - A synthetic retinoid Am80 (tamibarotene) rescues the memory deficit caused by
      scopolamine in a passive avoidance paradigm.
AB  - Memory deficit in rats treated with scopolamine was rescued by several synthetic
      retinoids, RAR-ligands (Am80, Am555S, Tp80) and an RXR-ligand (HX630). These
      results may have implications for the treatment of Alzheimer's disease, age
      related dementia, Parkinson's disease, and other neurological disorders.

PMID- 15516746
TI  - Equilibrium studies on chromium(III) complexes of salicylic acid and salicylic
      acid derivatives in aqueous solution.
AB  - The complexes of chromium(III) ion formed by salicylic acid, SA(H(2)L), and its
      derivatives (H(2)L): 5-nitrosalicylic acid (5-NSA), 5-sulphosalicylic acid (5
      SSA) were investigated by means of potentiometry and spectroscopy, at 25 degrees
      C and in ionic strength of 0.1 M KNO(3) and 0.1 M KCl, respectively. Over the
      acidic pH range, the coordination of Cr(III) ion to SA and its derivatives in 1 :
      1 mole ratio occurs, CrL(+) type complex is formed. In the excess of ligand, the
      coordination of the second ligand molecule is somewhat hindered; as a result
      CrL(HL) type complex occurs. Their existences were verified and their formation
      constants were determined. At near neutral pH, CrL(OH) and CrL(HL)(OH)(-) type
      hydroxo complexes formed by hydrolytic equilibria and their formation constants
      were also defined. The stabilities of Cr(III) complexes of SA and its derivatives
      decrease in the following order: SA>5-SSA>5-NSA. The formation constants of
      Cr(III) complexes of SA and its derivatives are in comparable ranges with the
      corresponding complexes of the 2,x-dihydroxybenzoic acid (2,x-DHBA) of Cr(III)
      ion. The stabilities of SA complexes for V(IV), Cr(III) and Fe(III) ions that
      have similar ionic radii, increase in the order VOL<CrL(+)<FeL(+). It is
      worthwhile noting that the binding ability of Cr(III) to salicylate ion is four
      orders of magnitude higher than to transferin, which is a blood serum protein and
      is associated with insulin action.

PMID- 15516747
TI  - Regioselective synthesis of 6-alkyl- and 6-prenylpolyhydroxyisoflavones and 6
      alkylcoumaronochromone derivatives.
AB  - The palladium-catalyzed coupling reaction of 6-iodoisoflavone, prepared from 3'
      iodoacetophenone derivative, with 2-methyl-3-butyn-2-ol gave 6-alkynylisoflavone
      derivative, which was hydrogenated to give 6-alkylhydroxyisoflavone (luteone
      hydrate) (2). Dehydration of 2 gave 2',4',5,7-tetrahydroxy-6-prenylisoflavone
      (luteone) (1). Wighteone hydrate (3) was also synthesized from 6
      iodotris(benzyloxy)isoflavone in a similar manner. 6-Alkyl-4'5,7-trihydroxy
      coumaronochromone (4) was synthesized by oxidative cyclization of 2 with o
      chloranil.

PMID- 15516748
TI  - A pharmacokinetic model for ocular drug delivery.
AB  - A pharmacokinetic model of ocular drug delivery has been developed for describing
      the elimination and distribution of ocular drugs in the eye. The model, based on
      Fick's second law of diffusion, assumes a modified cylindrical eye with three
      pathways for drug transport across the surface of the eye: the anterior aqueous
      chamber, the posterior aqueous chamber and the retina/choroids/scleral membrane
      covering the vitreous body. The model parameters such as the diffusion
      coefficient and the partition coefficient in various eye tissues can be evaluated
      from the in vitro membrane penetration experiments using a side-by-side diffusion
      cell system. The diffusion coefficient for a drug is also predicted by taking
      account of the effect of the molecular weight of model compounds. The present
      ocular pharmacokinetic model, which can predict the local concentration
      distribution in the eye, has well described the in vivo concentration profile in
      the various eye tissues, the lens, the aqueous humor and the vitreous body,
      following not only topical eye drop instillation but systemic administration as
      well. The present model also simulates the effects of binding and metabolism in
      the eye as well as the individual difference in ocular functions and structure
      such as cataract surgery and vitreous fluidity on the distribution and
      elimination of drug molecules in the eye.

PMID- 15516749
TI  - Phytochemical analysis of anti-atherogenic constituents of Xue-Fu-Zhu-Yu-Tang
      using HPLC-DAD-ESI-MS.
AB  - Xue-Fu-Zhu-Yu-Tang is a famous traditional Chinese medicine (TCM) formula for
      treating cardiovascular disease and related ailments in China for centuries. To
      profile the phytochemical constituents of the formula, an HPLC-DAD-ESI-MS
      analytical method has been developed to separate and determinate the medium- or
      non-polar fraction of the decoction, which has been demonstrated potency to lower
      the serum total triglyceride concentration, strongly decrease the TXA(2)/PGI(2)
      ratio and attenuate production of proinflammatory cytokines in high cholesterol
      fed rats. By comparing their retention time, UV and MS data with those obtained
      from the authentic compounds, ferulic acid (1), naringin (2), neohesperindin (3),
      naringenin (8), marmin (13), senkyunolide A (14), dehydrosafynol (16), safynol
      (17) and Z-ligustlide (18) are unequivocally determined. Moreover, additional
      thirteen compounds are tentatively identified as senkyunolide I (4), senkyunolide
      H (5), poncirin (7), benzoylpaeoniflorin (10), (Z)-6,7-epoxyligustilide (11),
      senkyunolide G (12), 2-methoxy-safynol (15), cnidilide (19), tangeritin (20),
      saikosaponin b(2) (21), 29-O-acetylsaikosaponin b(2) (22), saikosaponin b(1) (23)
      and auraptene (24), according to the comparison of their UV and MS data with the
      published data. The present study provides an approach to rapidly characterize
      bioactive constituents in TCM formulae.

PMID- 15516750
TI  - Mechanochemical solid-state polymerization (XI): effect of water-insoluble
      pharmaceutical aids on drug release from mechanically synthesized polymeric
      prodrugs.
AB  - We discuss here the effect of water-insoluble pharmaceutical aids on the nature
      of drug release from composite polymeric prodrugs synthesized by mechanochemical
      solid-state polymerization. Magnesium stearate (Mgst) and hydrogen castor oil
      (HCO) were used as water-insoluble pharmaceutical aids. Composite polymeric
      prodrugs were synthesized by the mechanochemical solid-state polymerization of a
      vinyl monomer of 5-fluorouracil (I) in the presence of Mgst or HCO. The molecular
      weight of the resulting polymeric prodrugs increased with increasing the content
      of Mgst or HCO. Prodrug hydrolysis was carried out in a heterogeneous system in
      phosphate buffer at pH 6.8 and 37 degrees C. The rate of drug release from the
      composite polymeric prodrug containing Mgst (Poly-Mgst) was faster than that from
      polymeric prodrug containing no pharmaceutical aids (Poly-Non), while hydrolysis
      of the composite polymeric prodrug containing HCO (Poly-HCO) was slower than Poly
      Non. Scanning electron microscope (SEM) photos showed the surface of Poly-HCO was
      smoother than that of Poly-Non and Poly-Mgst. It was suggested that the slower
      drug release from Poly-HCO may be responsible for the smaller specific surface
      area than that of Poly-Non. It was also shown that the rate of drug release from
      the composite polymeric prodrugs decreases with increasing the content of Mgst or
      HCO. Hence, novel composite polymeric prodrugs with a variety of drug release
      rates can be prepared by mechanochemical solid-state polymerization in a totally
      dry process.

PMID- 15516752
TI  - Simultaneous comparison of relative reactivities of twelve major anthocyanins in
      bilberry towards reactive nitrogen species.
AB  - The reactivities of twelve major anthocyanins identified in bilberry extracts
      towards nitric oxide (NO.) and peroxynitrite (ONOO-) were studied in vitro using
      capillary zone electrophoresis (CZE). The reactivities of the anthocyanins
      towards NO. were slightly weak compared with that of (+)-catechin as a reference
      antioxidant under anaerobic conditions except delphinidin glycosides (Dp3glys).
      The reactivities of other anthocyanins were not significantly affected by either
      the aglycon structure or the type of sugar moiety. Under aerobic conditions, all
      anthocyanins and catechin showed significant enhancement of the reactivity,
      indicating that they reacted with other reactive species secondarily generated
      from NO. . Dp3glys showed rather extraordinally high reactivity towards ONOO-
      compared to other anthocyanins which showed approximately two times low
      reactivity than catechin when compared with IC50. Structural divergence in the
      reactivity was also small for all these anthocyanins.

PMID- 15516751
TI  - Constituents of Crinoidea, 4. Isolation and structure of ceramides and
      glucocerebrosides from the feather star Comanthus japonica.
AB  - Five ceramides, JC-1-JC-5, and four glucocerebrosides, JCer-1-JCer-4, have been
      isolated from their parent ceramide and glucocerebroside molecular species JC and
      JCer obtained from the less polar lipid fraction of the chloroform/methanol
      extract of the feather star Comanthus japonica. The structures of these
      sphingolipids have been determined on the basis of chemical and spectroscopic
      evidence. Reversed-phase HPLC was effective at isolating these sphingolipids,
      revealing very close resemblance in their structures. JC-1, JC-3, JC-4, JC-5 and
      JCer-2, JCer-4 are newly found ceramides and glucocerebrosides, respectively.

PMID- 15516753
TI  - Preparation of new nitrogen-bridged heterocycles. 56. Syntheses and reactions of
      1-[2,2-bis(alkylthio)-1-(ethoxycarbonylacetyl)vinyl]pyridinium salts.
AB  - The title compounds, readily available from the S-alkylation of pyridinium 1
      [alkylthio(thiocarbonyl)](ethoxycarbonylacetyl)methylides with alkyl halides or
      alkyl bromoacetates, were treated with a base and then a dehydrogenating agent to
      provide some unique products such as 3-[bis(alkylthio)methylene]-2(3H)
      indolizinones and dialkyl 7-methyl-4-oxo-1,4,8,8a-tetrahydro-1,4-thiazino[3,4,5
      cd]indolizine-1,5-dicarboxylates. On the other hand, similar reaction of these
      pyridinium salts in the absence of the dehydrogenating agent afforded alkyl 2
      hydroxyindlizine-3-carboxythiolates, whose yields were increased by adding
      trifluoroacetic acid to the reaction mixture. The structures of some products
      were confirmed by the X-ray analyses.

PMID- 15516754
TI  - Application of LC-NMR for characterization of rat urinary metabolites of
      zonampanel monohydrate (YM872).
AB  - Zonampanel monohydrate (YM872) has a potent and selective antagonistic effect on
      the glutamate receptor subtype, alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionic acid (AMPA) receptor. Metabolic fingerprinting in rat urine after a
      single intravenous administration of (14)C-labeled YM872 ((14)C-YM872) revealed
      the presence of two metabolites, R1 and R2. The two metabolites were semi
      purified by preparative HPLC from rat urine after a single intravenous
      administration of non-labeled YM872, and their structures were elucidated by
      various instrumental analyses involving LC-NMR. The results showed that R1 and R2
      have a hydroxyamino group and an amino group at the C-7 position of the
      quinoxalinedione skeleton, respectively. Therefore, the proposed metabolic
      pathway of YM872 in rats involves the reduction of the nitro group to a
      hydroxyamino group and then subsequent reduction to an amino group.

PMID- 15516756
TI  - Synthesis and pharmacological evaluation of novel arylpiperazine derivatives as
      nonsteroidal androgen receptor antagonists.
AB  - The search for novel antiandrogens by high-throughput screening (HTS) of the
      Yamanouchi chemical library led to the discovery of the lead compound (5), which
      possesses an arylmorpholine moiety. Through the optimization of the lead compound
      (5), we have found a series of novel arylpiperazine derivatives. Among them, 4-[4
      cyano-(3-trifluoromethyl)phenyl]-N-(4-fluorophenyl)piperazine-1-carboxamide (22;
      YM-92088) exhibited a potent AR antagonistic activity with an IC(50) value of
      0.47 microM in the reporter assay, which is more potent than bicalutamide (4)
      which has an IC(50) value of 0.89 microM.

PMID- 15516755
TI  - Antiallergic agents from natural sources 9. Inhibition of nitric oxide production
      by novel chalcone derivatives from Mallotus philippinensis (Euphorbiaceae).
AB  - Three novel chalcone derivatives, mallotophilippens C (1), D (2) and E (3) were
      isolated from the fruits of Mallotus philippinensis MUELL. ARG. These compounds
      were identified, using chemical and spectral data, as 1-[6-(3,7-dimethyl-octa-2,6
      dienyl)-5,7-dihydroxy-2,2-dimethyl-2H-chromen-8-yl]-3-(4-hydroxy-phenyl)
      propenone, 3-(3,4-dihydroxy-phenyl)-1-[6-(3,7-dimethyl-octa-2,6-dienyl)-5,7
      dihydroxy-2,2-dimethyl-2H-chromen-8-yl]-propenone and 1-[5,7-dihydroxy-2-methyl-6
      (3-methyl-but-2-enyl)-2-(4-methyl-pent-3-enyl)-2H-chromen-8-yl]-3-(3,4-dihydroxy
      phenyl)-propenone, respectively. They inhibited nitric oxide (NO) production and
      inducible NO synthase (iNOS) gene expression by a murine macrophage-like cell
      line (RAW 264.7), which was activated by lipopolysaccharide (LPS) and recombinant
      mouse interferon-gamma (IFN-gamma). Furthermore, they downregulated
      cyclooxygenase-2 (COX-2) gene, interleukin-6 (IL-6) gene and interleukin-1beta
      (IL-1beta) gene expression. These results suggest that they have anti
      inflammatory and immunoregulatory effects.

PMID- 15516757
TI  - Synthesis of unnatural 1-methyl-2-quinolone derivatives.
AB  - Unnatural 1-methyl-2-quinolone derivatives were synthesized by regioselective C-C
      bond formation. When 1-methyl-3,6,8-trinitro-2-quinolone (TNQ) was treated with
      enamines, nucleophilic addition readily occurred at the 4-position, and
      succeeding hydrolysis of enamine moiety followed by elimination of nitrous acid
      furnished 4-acylmethyl-1-methyl-6,8-dinitro-2-quinolones. The same products could
      be prepared by the reaction of TNQ with ketones in the presence of triethylamine.
      The present reaction enabled the introduction of various kinds of acylmethyl
      groups substituted with alkyl, aryl or hetaryl groups.

PMID- 15516758
TI  - Oligomeric stilbenes from the root of Caragana stenophylla.
AB  - Caragaphenol A (1), a new trimeric stilbene, was isolated from the roots of
      Caragana stenophylla (Leguminosae) along with three known oligomeric stilbenes:
      (+)-alpha-viniferin (2), miyabenol C (3) and kobophenol A (4). The
      stereostructure of 1 was elucidated by one- and two-dimensional (1D- and 2D-)-NMR
      spectral studies.

PMID- 15516759
TI  - Antimicrobial screening and quantitative determination of benzoic acid derivative
      of Gomphrena celosioides by TLC-densitometry.
AB  - The antimicrobial activity of ethanolic extract and pure compounds of Gomphrena
      celosioides have been screened by Kirby-Bauer method. Quantitative determination
      of 4-hydroxy-3-methoxy-benzoic acid in stems, leaves, flowers and roots was
      established by TLC-densitometry. Results showed significant activity against
      Staphylococcus aureus and Salmonella typhi. There were no significant differences
      in the determined benzoic acid derivative.

PMID- 15516760
TI  - Chemical constituents of a marine soft coral of the genus Lobophytum.
AB  - Chemical investigations on the marine soft coral Lobophytum sp., collected from
      the Andaman and Nicobar Islands, yielded two new acyl glycerol monoalkyl ethers
      along with two known compounds of this series (1a-d), and a new ceramide (4a).
      The structures of the new and known compounds were elucidated on the basis of
      extensive spectroscopic studies and chemical reactions.

PMID- 15516761
TI  - New insecticidal amides from petroleum ether extract of dried Piper nigrum L.
      whole fruits.
AB  - The petroleum ether extract of dried ground whole fruits of Piper nigrum L.
      afforded 20 compounds (1-20) including two new insecticidal amides named as
      pipnoohine (1), and pipyahyine (2), seven reported for the first time from this
      plant (12, 13, 15-17, 19, 20), and eleven known compounds (3-11, 14, 18). The
      structure of 1 has been elucidated as (2E,4E,12Z)-N-(4-methylpentyl)octadeca
      2,4,12-trienamide and that of 2 as (2E,4E,11E)-12-(benzo[1,3]dioxol-5-yl)-N-(3
      methylbutyl)dodeca-2,4,11-trien-amide through extensive ID-, 2D-NMR spectral
      studies and chemical reactions. The known compounds have been identified through
      comparison of their spectral data with those reported in literature. 1 and 2
      exhibited toxicity at 35.0 and 30.0 ppm respectively against fourth instar larvae
      of Aedes aegypti L. by WHO method.

PMID- 15516762
TI  - A new steroidal saponin from Dioscorea cayenensis.
AB  - The new 26-O-beta-D-glucopyranosyl-3beta,26-dihydroxy-20,22-seco-25(R)-furost-5
      en-20,22-dione-3-O-alpha-L-rhamnopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-
      >4)-[alpha-L-rhamnopyranosyl-(1-->2)]-beta-D-glucopyranoside (1), along with the
      known methyl protodioscin (2), asperoside (3) and prosapogenin A of dioscin (4)
      were isolated from the rhizomes of Dioscorea cayenensis LAM.-HOLL
      (Dioscoreaceae). Their structures were established mainly on the basis of 600 MHz
      2D-NMR spectral data. 4 exhibited antifungal activity against the human
      pathogenic yeasts Candida albicans, C. glabrata and C. tropicalis (MICs of 20.8,
      6.25, 25 microg/ml, respectively), whereas saponins 1-3 were inactive.

PMID- 15516763
TI  - Two new acylated iridoid glucosides from the aerial parts of Paederia scandens.
AB  - Two new acylated iridoid glucosides were isolated from the aerial parts of
      Paederia scandens along with six known iridoid glucosides. The structures of two
      new compounds were elucidated as 6'-O-E-feruloylmonotropein (1) and 10-O-E
      feruloylmonotropein (2) by spectroscopic methods.

PMID- 15516764
TI  - Two novel dicoumaro-p-menthanes from Gerbera piloselloides (L.) CASS.
AB  - Two new type dicoumarins (dicoumaro-p-menthanes), named dibothrioclinins I (1)
      and II (2) were isolated from the roots and rhizomes of Gerbera piloselloides
      (L.) CASS., collected in Yunnan Province, China. Their structures were elucidated
      on the basis of MS, 1D ((1)H-NMR, (13)C-NMR, DEPT and NOE) and 2D ((1)H-(1)H
      COSY, HMQC, HMBC) NMR spectral analyses. The relative structures of the two
      compounds were established by NOE difference spectroscopy and further confirmed
      by single-crystal X-ray diffraction studies.

PMID- 15516765
TI  - A new 2-arylbenzofuran with antioxidant activity from the black colored rice
      (Oryza sativa L.) bran.
AB  - From the black colored rice bran of Oryza sativa cv. Heugjinjubyeo, a new 2
      arylbenzofuran, 2-(3,4-dihydroxyphenyl)-4,6-dihydroxybenzofuran-3-carboxylic acid
      methyl ester, oryzafuran (1), was isolated. Its structure has been elucidated on
      the basis of spectral data. This compound showed strong antioxidative activity in
      a 1,1-diphenyl-2-picrylhydrazyl free radical scavenging assay.

PMID- 15516766
TI  - Preparation of enantiopure norbornane ligands bearing both (2S,3S)
      bis(phosphinomethyl) and 7-syn-oxygen functional groups and an application to
      rhodium-catalyzed asymmetric hydrogenation.
AB  - Enantiopure bicyclo[2.2.1]heptane derivatives having both (2S,3S)
      bis[(diphenylphosphino)methyl] and 7-syn-oxygen functional groups were
      synthesized by using diastereoselective Diels-Alder reaction of di-(1R)-menthyl
      fumarate and 5-trimethylsilylcyclopentadiene followed by silver-promoted
      stereospecific frame rearrangement of a bromolactone intermediate. Rhodium
      catalyzed asymmetric hydrogenations were carried out using the diphosphines as a
      chiral ligand.

PMID- 15516767
TI  - Microbial metabolism. Part 5. Dihydrokawain.
AB  - Preparative scale fermentation of (6S)-dihydrokawain (1) with Rhizopus arrhizus
      (ATCC 11145) gave 3'-hydroxydihydrokawain (2) and (8S)-hydroxydihydrokawain (3).
      Structure elucidation of the metabolites was based on spectroscopic data. The C-8
      absolute configuration of (3) was assessed via its Mosher's esters.

PMID- 15516768
TI  - New lanostane-type triterpenes from Fomes officinalis.
AB  - Five new lanostane-type triterpenes, named fomefficinic acid A-E (1-5), were
      isolated from the dried sclerotium of Fomes officinalis, respectively. Their
      structures were established as 24-methylene-3-oxo-lanost-8-en-21-oic acid (1),
      3alpha,15alpha-dihydroxy-24-methylene-lanosta-7,9(11)-dien-21-oic acid (2),
      3alpha,15alpha-dihydroxy-24-methylene-lanost-8-en-21-oic acid (3), 15alpha
      hydroxy-3-oxo-24-methylenelanost-8-en-21-oic acid (4), 15alpha-acetoxy-3-oxo-24
      methylenelanosta-7,9(11)-dien-21-oic acid (5), by spectral analysis and chemical
      methods as well as comparison with known compounds.

PMID- 15516769
TI  - Metal elution and content of fused slags produced from incinerated ash.
AB  - In recent years, trials to reuse fused slags, obtained through the further
      treatment of incinerated ash produced in the process of the disposal of garbage
      or sewer sludge, such as for building materials including bricks, have drawn
      attention. To establish the safety of using such substances, elution tests for
      metals and metal contents were investigated in this study. As the result of
      examining 13 slags, which were made by different methods, little elution of toxic
      metals was found in the elution tests when water was used as a solvent. However
      when acid was used, there was a tendency for the elution of many kinds of metals
      to become greater. On other hand, the results of content measurements showed that
      arsenic and selenium, which were not seen to be eluted from any of the slags
      tested, were detected; and that aluminum and manganese existed in the slags in
      high concentrations.

PMID- 15516770
TI  - Chemical constituents of Malagasy liverworts, part II: mastigophoric acid methyl
      ester of biogenetic interest from Mastigophora diclados (Lepicoleaceae Subf.
      Mastigophoroideae).
AB  - In the course of our chemotaxonomic study of the liverworts growing in
      Madagascar, mastigophoric acid methyl ester, along with eleven known compounds
      were isolated from Mastigophora diclados. Isolated metabolites showed that the
      Malagasy Mastigophora is more related to the samples from Borneo and Japan than
      to the Taiwanese or Malaysian ones. The biosynthesis of the herbertane type
      sesquiterpenoids from Mastigophora diclados is suggested to be similar to those
      found in the genus Herbertus. The herbertane-type sesquiterpenoids were screened
      for Staphylococcus aureus strain inhibition.

PMID- 15516771
TI  - Simple synthesis of deuterium and 13C labeled trifluoromethyl phenyldiazirine
      derivatives as stable isotope tags for mass spectrometry.
AB  - The synthesis of trifluoromethyl diazirine with a stable isotope tag is reported.
      We found that both Friedel-Crafts acylation and reduction of aryl carbonyl to
      methylene, using commercially available stable-isotope reagents, were utilized
      for the synthesis of diazirinyl fatty acid derivatives. The stable isotope
      labeled diazirine may be valuable for identifying binding sites by mass
      spectrometry.

PMID- 15516772
TI  - Structures of new aromatics glycosides from a Japanese folk medicine, the roots
      of Angelica furcijuga.
AB  - Three new aromatics glycosides, hyuganosides II, IIIa, and IIIb, were isolated
      from a Japanese folk medicine, the roots of Angelica furcijuga KITAGAWA. The
      structures of the new glycosides were determined on the basis of chemical and
      physicochemical evidence.

PMID- 15516773
TI  - Molecular weight determination of hypromellose acetate succinate (HPMCAS) using
      size exclusion chromatography with a multi-angle laser light scattering detector.
AB  - The molecular weight of hypromellose acetate succinate (HPMCAS), a polymer used
      for enteric coating, was determined by means of size exclusion chromatography
      with a multi-angle laser light scattering detector. The weight-average molecular
      weight (Mw) of several lots and grades ranged approximately from 17000 to 20000,
      and the number-average molecular weight (Mn) was around 13000. The inter-day
      precision of measurement, in terms of the coefficient of variation, was less than
      5%.

PMID- 15516774
TI  - A novel method for predicting disintegration time in the mouth of rapidly
      disintegrating tablet by compaction analysis using TabAll.
AB  - A tableting process analyzer (TabAll) was used to predict disintegration time in
      the mouth of rapidly disintegrating tablet. Analyzer profiles recorded upper
      punch displacement and die wall force encountered during tablet processing.
      Changes in the mixing ratio of spherical sugar granules and microcrystalline
      cellulose or lactose affected upper punch displacement and die wall force
      profiles. Analysis of the compaction process revealed a strong association
      between disintegration time in the mouth and stationary time, relaxation time of
      upper punch displacement, and relaxation time of die wall force; disintegration
      time in the mouth decreased as the three parameters increased. Thus, analysis of
      the compaction process is useful for predicting disintegration time in the mouth
      of rapidly disintegrating tablet, which can assist the formulation of new rapidly
      disintegrating tablets.

PMID- 15516775
TI  - Taccasterosides A-C, novel C28-sterol oligoglucosides from the rhizomes of Tacca
      chantrieri.
AB  - Three novel C(28)-sterol oligoglucosides, named taccasterosides A-C (1-3), were
      isolated from the rhizomes of Tacca chantrieri (Taccaceae). Their structures were
      determined by detailed spectroscopic analysis, including 2D NMR data, and a few
      chemical transformations.

PMID- 15516776
TI  - Long-term effects of octreotide on pituitary gigantism: its analgesic action on
      cluster headache.
AB  - We report the case of 19-year-old man with pituitary gigantism due to growth
      hormone-producing pituitary macroadenoma. The patient complained of recurrent
      headache and excessive growth spurt since age 15. Octreotide administration was
      initiated following transsphenoidal pituitary adenomectomy. Octreotide injection
      for 4 years efficaciously reduced the size of remnant adenoma as well as serum
      growth hormone levels. Notably, octreotide exhibited a potent analgesic effect on
      his intractable cluster headache that has continued even after reduction of the
      adenoma volume. The analgesic effect lasted 2 to 6 hours after each injection and
      no tachyphylaxis to octreotide appeared during 4-year treatment. To characterize
      the headache and the pain intensity, analgesic drugs including octreotide,
      lidocaine, morphine and thiopental were tested using a visual analogue scale
      (VAS) evaluation, with the result that octreotide exhibited a prompt and complete
      disappearance of the headache. Headache relief was in part reproduced by morphine
      injection (56% reduction) but not by lidocaine or thiopental. The present case
      suggests that the intractable headache associated with pituitary gigantism is
      possibly related to the endogenous opioid system. Thus, the headache control by
      octreotide is clinically helpful for continuation of the self-injection regimen.

PMID- 15516777
TI  - Medullary thyroid carcinoma: nationwide Japanese survey of 634 cases in 1996 and
      271 cases in 2002.
AB  - Medullary thyroid carcinoma (MTC) occurs sporadically or as an inherited disease,
      with the latter occurring in the form of multiple endocrine neoplasia (MEN) type
      2A, MEN type 2B, or familial non-MEN medullary carcinoma (FMTC). MTC is inherited
      as an autosomal dominant trait and is associated with germline mutations of the
      RET proto-oncogene. Genetic testing identifies carriers of the mutant gene and
      enables preventive thyroidectomy. A nationwide questionnaire-based survey was
      conducted in 1996 and again in 2002, and we report here the results of the two
      surveys that characterize the clinical course of the inherited form of MTC. The
      data show a higher rate of inherited MTC than previously described, although
      MEN2A was found to be the most common inherited form of MTC, the same as in
      earlier studies. The most important finding was the difference in method of
      detection of MTC between the two surveys. Since the discovery of the genetic
      association with the disease, genetic testing has become the diagnostic method of
      choice, replacing indicators such as neck mass and elevated non-stimulated serum
      calcitonin level. Genetic testing enables early detection of the disease, which
      provides patients with the possibility of better outcome.

PMID- 15516778
TI  - Spindle cell metaplasia in follicular adenoma of the thyroid gland: case report
      and review of the literature.
AB  - Spindle cell tumors and reactive proliferations of the thyroid gland are rarely
      reported. In this report, we described a case of follicular adenoma with spindle
      cell component. The spindle cell proliferation constituted more than 90% of the
      4.0 cm lesion and showed fascicular pattern with focal areas of collagenous
      stroma and hyalinized blood vessels. There was a transition from follicle like
      glandular structure to fascicular pattern. There was no mitosis and necrosis.
      Immunoreactivity with thyroglobulin proved that the spindle cell proliferation is
      of follicular origin. Also strong thyroglobulin and cytokeratin positivity of
      glandular areas and the gradual decrease in positivity of spindle cells showed
      epithelial-mesenchymal transformation/spindle cell metaplasia of the thyroid. We
      thought that it is important to differentiate spindle cell metaplasia in
      follicular lesions, especially follicular adenoma, from malignant thyroid
      neoplasms.

PMID- 15516779
TI  - Unilateral active adrenal tuberculosis featuring persistent intermittent fever.
AB  - The adrenal gland is one of the organs which tuberculosis infects. In most
      clinical settings bilateral adrenal tuberculosis has been clarified after adrenal
      insufficiency is overt. On the contrary, active adrenal tuberculosis is rarely
      detected during the survey of infectious disease. A 68-year-old man was admitted
      because of intermittent fever. The fever had continued for the last 3 months. The
      intermittent fever was accompanied with leukocytosis and elevation of C-reactive
      protein. Serum soluble interleukin-2 receptor was 1920 U/ml, and beta2
      microglobulin was 4.0 mg/l. Bacterial cultures of blood, sputa, urine, bone
      marrow and cerebrospinal fluid did not show any particular bacteria.
      Mycobacterium tuberculosis was negative in culture of sputa, and there was no
      tuberculin reaction. Plasma ACTH and serum cortisol were 18.5 pmol/l and 527.0
      nmol/l, respectively. Abdominal CT scan showed right adrenal mass with a size of
      28 x 20 mm, which was low density and had a well-encapsulated homogenous
      appearance. After the adrenalectomy, histology verified active adrenal
      tuberculosis. The intermittent fever disappeared, and white blood cells and C
      reactive protein normalized. These findings indicate an atypical, rare case of
      unilateral, active adrenal tuberculosis closely linked to intermittent fever, and
      without any other organ involvement.

PMID- 15516780
TI  - The plasminogen activator system in young and lean women with polycystic ovary
      syndrome.
AB  - The purpose of the study was to evaluate the plasminogen activator inhibitor-1
      (PAI-1) levels and PAI-1 activity in young and lean women with PCOS and to
      compare with controls matched for age and weight. Thirty two women with PCOS and
      25 weight and age-matched healthy controls participated in this study. Patients
      were evaluated clinically and by pelvic ultrasound and fasting blood samples were
      taken for hematological and biochemical tests. Fasting insulin, glucose, lipid
      profile, FSH, LH, PRL, testosterone, SHBG, 17-hydroxyprogesterone,
      androstenedione, PAI-1 antigen; PAI-1 activity, insulin sensitivity indices (HOMA
      and QUICKI) were measured. PAI-1 Ag and activity were significantly higher in
      PCOS women than healthy control group. PAI-1 levels were directly correlated with
      BMI, insulin levels and insulin sensitivity indices. PAI-1 activity was also
      correlated with insulin levels and insulin resistance. As a conclusion PAI-1 Ag
      levels and activity were increased in lean PCOS women and these were directly
      correlated with insulin resistance. The finding may contribute to evidence of
      increase risk of cardiovascular disease and anovulatory infertility in PCOS
      women.

PMID- 15516781
TI  - Two cases of Allgrove syndrome with mutations in the AAAS gene.
AB  - Allgrove syndrome is a rare autosomal recessive disorder characterized by the
      triad of adrenal insufficiency, achalasia and alacrima. This syndrome, also known
      as triple A syndrome, is now known to be caused by mutations in the AAAS gene. In
      the present study, we report two new patients of Allgrove syndrome with mutations
      in the AAAS gene. Patient 1 was a 22-year-old Japanese woman, born to
      consanguineous parents. She was confirmed to have adrenal insufficiency at the
      age of 3 years and 6 months. She developed alacrima and bilateral optic nerve
      atrophy at the age of 8 years. She had been noticed to have dysphagia. Based on
      these findings, she was diagnosed as having Allgrove syndrome. Mutation analysis
      revealed a novel homozygous point mutation in exon 7 of her AAAS gene, changing
      codon 194 encoding Arg (CGA) to a stop codon (TGA) (R194X). Patient 2 was a 7
      year-old Japanese boy, born to consanguineous parents. At the age of 1 year, he
      was noticed to be unable to produce tears. He was confirmed to have adrenal
      insufficiency, mental retardation and spastic diplegia at the age of 5 years and
      4 months. He was tentatively diagnosed as having Allgrove syndrome, although he
      has never complained of dysphasia. Mutation analysis revealed a homozygous point
      mutation in exon 4 of his AAAS gene, changing codon 119 encoding Arg (CGA) to a
      stop codon (TGA) (R119X). Both of the R119X and R194X mutations are predicted to
      result in truncated and non-functioning ALADIN proteins, and thus the diagnosis
      of Allgrove syndrome was confirmed by the mutation analyses. These findings
      indicate that there exist significant clinical variability and mutational
      heterogeneities in Japanese patients with this syndrome.

PMID- 15516783
TI  - Use of gadolinium contrast adrenal venography for the assessment of primary
      aldosteronism in a patient with iodine allergy.
AB  - Primary aldosteronism is a relatively common cause of secondary hypertension. It
      is often important to diagnose this disease accurately, since appropriate
      surgical therapy may result in cure of the disease. Assessment of the laterality
      of adrenal hyperfunction is possible using adrenal venous sampling of steroid
      hormones, but this procedure may not be feasible in patients with allergy to
      iodinated radiocontrast agents. In this paper, we report a patient with primary
      aldosteronism who was found to have bilateral adrenal tumors on CT. Because
      preoperative localization of the hyperfunctioning tumor was important, adrenal
      venous sampling and venography was performed by a highly-experienced radiologist
      using the MRI contrast agent gadolinium. After reviewing the data, the patient
      received a right adrenalectomy. This case report demonstrates that it was
      possible to perform adrenal venography using gadolinium in this patient, however
      the safety and efficacy should be re-assessed in individual cases.

PMID- 15516782
TI  - Complications in adults with growth hormone deficiency--a survey study in Japan.
AB  - It has been reported that adult patients with growth hormone deficiency (GHD)
      have increased risk factors for cardiovascular disorders in Western countries.
      However, data on this issue in Japan have not been fully investigated. To clarify
      the situation on this issue in Japan, a nationwide questionnaire survey was
      conducted by Study Group of Hypothalamo-Pituitary Disease, and medical records of
      863 adult patients were recruited. The incidences of complications and risk
      factors for cardiovascular diseases were compared between GH deficient patients
      (GHD, n = 494) and GH intact patients (GHI, n = 369). The incidence of myocardial
      infarction was higher in GHD (1.2%) than in GHI (0.8%), but not significantly.
      The incidences of angina pectoris and liver dysfunction were significantly higher
      in GHD than in GHI (2.8 vs 0.8%, p = 0.048, and 11.9 vs 5.5%, p<0.0001,
      respectively). The prevalences of obesity and hyperlipidemia (HL) were
      significantly higher in GHD (p = 0.004, p<0.001, respectively). Combinations of
      HL plus diabetes mellitus (DM) or hypertension (HT) were more common in GHD than
      in GHI (HL + DM; 7.2 vs. 2.9%, HL + HT; 10.9 vs. 2.9%). These results indicated
      that GH deficiency have an increased prevalence of cardiovascular risk factors in
      Japanese similar to Western countries, and suggested that GH supplement therapy
      may be needed to reduce those complications.

PMID- 15516784
TI  - Association study of human MTH1 gene polymorphisms with type 1 diabetes mellitus.
AB  - Reactive oxygen species are considered to play a role in the development of
      diabetes mellitus and its complications. Human MTH1 (mutT homologue 1) has 8-oxo
      7,8-dihydrodeoxyguanosine triphosphatase activity, which repairs oxidized forms
      of dGTP. This enzyme is known to have a thermolabile Met83 variant. We examined
      whether Val83Met polymorphism of human MTH1 gene is associated with type 1
      diabetes mellitus. We recruited 156 type 1 diabetic patients (59 males and 97
      females). The polymorphism was analyzed by restriction fragment length
      polymorphism analysis with Nsi I. The Met/Met genotype at codon 83 was very rare
      in both control and patient groups. Val/Met genotype tended to be more frequent
      in the whole type 1 diabetic patients than in controls. When subjects were
      divided into subgroups according to gender, there were no differences in the
      genotype and allele frequencies between patients and controls in males. On the
      other hand, in female type 1 diabetic patients, the Val/Met genotype was more
      frequent than in female controls (corrected P = 0.102). The Met allele was
      significantly more frequent in female type 1 diabetic patients than in female
      controls (corrected P = 0.022). Our results suggested that the Met allele at
      codon 83 of MTH1 gene might be involved in the development of type 1 diabetes
      mellitus in the Japanese female population.

PMID- 15516785
TI  - Progression of diabetic nephropathy enhances the plasma osteopontin level in type
      2 diabetic patients.
AB  - Osteopontin (OPN) is thought to play multiple roles in the progression of
      atherosclerotic plaque including diabetic vascular complications. However, it
      still remains unclear whether the level of OPN in vivo is indeed clinically
      associated with the progression of diabetic complications. This study evaluated
      whether the levels of OPN in plasma and urine are correlated with the progression
      of diabetic complications, such as retinopathy, neuropathy, and nephropathy in
      patients with type 2 diabetes. In 229 patients with type 2 diabetes, OPN level in
      plasma and urine was evaluated by both the severity of diabetic complications,
      such as retinopathy, neuropathy, and nephropathy, and the clinical
      characteristics and the substantial laboratory findings. Plasma OPN level
      increased significantly with aging and the progression of diabetic nephropathy,
      especially at the stage of renal failure (p<0.05). However, the level was not
      related to the progression of retinopathy or neuropathy, or to laboratory
      findings, such as HbA1c or serum lipids. In contrast, urinary OPN level was not
      associated with diabetic complications in any of the subjects. There was no
      correlation between the plasma and urinary values of OPN. The results established
      that the plasma OPN was elevated in proportion to the progression of diabetic
      nephropathy, indicating that the plasma concentration may be a potential
      diagnostic predictor of diabetic end-stage renal disease.

PMID- 15516786
TI  - Relationship between homocysteine and insulin resistance in women with polycystic
      ovary syndrome.
AB  - Hyperhomocysteinemia is a risk factor for atherosclerotic vascular diseases. It
      is known that plasma homocysteine levels are higher in polycystic ovary syndrome
      (PCOS) patients than in healthy subjects. The aim of our study was to determine
      the relationship between plasma homocysteine level and insulin resistance in
      women with PCOS. Twenty-nine patients (age, 23.90 +/- 5.86 years) and twenty-five
      healthy subjects (age, 25.24 +/- 4.28 years) were involved in the study. Plasma
      levels of fasting insulin, glucose, homocysteine, FSH, and LH levels were
      measured. A statistically significant difference in plasma concentrations of HOMA
      index, homocysteine, basal insulin levels and LH/FSH ratios was observed between
      groups (P = 0.001, P = 0.001, P = 0.001, and P = 0.01, respectively). There was
      no relationship between Hcy and the other variables. In multiple logistic
      regression analysis, age, BMI and insulin resistance were not predictors of Hcy.

PMID- 15516787
TI  - Establishment of a set of combined immunodeficient DA/Slc-Foxn1(rnu) Lyst(bg)
      congenic rat strains.
AB  - The congenitally athymic nude rat is used for studying cancer and transplantation
      owing to its hairlessness and T-cell defective function caused by the Foxn1(rnu)
      gene. However, NK cell activity of the nude rat is markedly increased. It is
      known that NK cells play a major role in rejection of xenografts and in
      cytotoxicity against tumor cells. Thus, the athymic nude rat with impaired NK
      cell activity should be a useful model for extensive studies. The DA
      Lyst(bg)/Lyst(bg) rat, a model for human Chediak-Higashi syndrome (CHS) is
      characterized by diluted-coat color and impairment of NK cell activity. We
      planned to establish a combined immunodeficient double mutant rat introgressed
      with the Foxn1(rnu) and Lyst(bg) genes and a set of congenic strains having an
      identical genetic backgrounds simultaneously. Based on the phenotypic and genetic
      characteristics of the parental rat strains, the new strains were produced using
      continuous backcross and diagnosis with molecular genetic techniques. Each
      disease gene was diagnosed with PCR-RFLP or the long-nested PCR method.
      Furthermore, we used a marker-assisted congenic strategy based on scanning the
      genetic backgrounds of the parental rats with 461 rat microsatellite markers. We
      think that the newly established DA/Slc-Foxn1(rnu)/Foxn1(rnu) Lyst(bg)/Lyst(bg)
      double mutant will be useful as a severe disease model for human CHS, and the set
      of DA/Slc-Foxn1(rnu) Lyst(bg) congenic strains which have impaired NK cell
      activity and/or defective T cell function should be useful for studying in cancer
      research, xenotransplantation, immune function and other wide-ranging studies.

PMID- 15516788
TI  - Comparison of ultrasonic vocalizations emitted by rodent pups.
AB  - Ultrasonic vocalizations (USVs) emitted by rodent pups, mouse, rat, Syrian
      hamster, vole, and Mongolian gerbil, were compared as a basic study for a
      screening test of anti-panic drugs. USVs of rodent pups, separated from their
      mother under a low temperature condition, were collected by Real-Time Spectrogram
      (RTS) apparatus, and transformed into spectrograms and power spectra by SIGNAL
      software. Waveforms of USVs emitted by the rodent pups showed several
      characteristic features, and species specificity of USVs was shown. We think that
      the species specificity might be due to differences of the anatomical structures
      in the respiratory tract and respiratory patterns in rodent pups.

PMID- 15516789
TI  - Comparative effects of recombinant acid sphingomyelinase administration by
      different routes in niemann-pick disease mice.
AB  - An inherited deficiency of acid sphingomyelinase (ASM) activity results in the
      Type A and B forms of Niemann-Pick disease (NPD). The aim of this study was to
      evaluate the effects of recombinant human ASM (rhASM) replacement therapy on the
      mouse model, by comparing different routes of administration. Eight NPD mice
      received rhASM via an intravenous injection (IV) administered at a dose of 1
      mg/kg and another group of 8 NPD mice received the same dose by subcutaneous
      injection (SC). The plasma levels of ASM activity in intravenously administered
      mice were significantly elevated immediately after injection. In contrast, in the
      subcutaneously injected mice, the level of ASM activity was maximal 6 h after
      injection. The levels of ASM activity in both groups had declined substantially
      by 2 days after injection. It was concluded that rhASM administered by
      subcutaneous injection is completely absorbed, and offers a similar efficacy to
      intravenously administered recombinant enzyme.

PMID- 15516790
TI  - Reversal of medetomidine-ketamine combination anesthesia in rabbits by
      atipamezole.
AB  - This study was performed to determine the optimal reversal dosage of atipamezole
      on medetomidine-ketamine combination anesthesia. The subject rabbits were divided
      into five groups (n=5/group), and all were anesthetized with intravenous
      medetomidine (0.35 mg/kg) and ketamine (5 mg/kg). Atipamezole was administered
      intravenously 35 min after administration of the medetomidine-ketamine mixture,
      at doses of a quarter, a half, equal, or two times higher than the preceding
      medetomidine -ketamine dose according to experimental group. Heart rate (HR),
      mean arterial pressure (MAP), respiratory rate (RR) and rectal temperature (RT)
      were measured every five minutes and the mean arousal time (MAT) was also
      recorded. This study revealed that the optimal atipamezole dosage to achieve
      reversal effects is equal to or double the dose of medetomidine. At these
      dosages, HR and MAP significantly recovered and MAT was significantly shortened
      with no side effects being observed (p<0.05).

PMID- 15516791
TI  - Fine mapping of a region of rat chromosome 12 close to the aspermia (as) locus
      and comparison with the human orthologous regions.
AB  - The aspermia mutation of the rat exhibits male sterility caused by arrest of
      spermatogenesis, which is controlled by an autosomal single recessive gene (as).
      The as locus has been mapped on rat chromosome 12. We recently identified a
      causative mutation for the aspermia phenotype of the as homozygous rats in the
      gene encoding Fkbp6, a member of the immunophilins FK506 binding proteins. In
      this paper, we report the fine mapping of the as locus by linkage analysis
      combined with comparative mapping using rat, mouse, and human genomic sequences
      and expression analysis of genes located in the as region. We constructed a fine
      linkage map of the region of rat chromosome 12 close to the as locus by using 13
      microsatellite markers and localized the as locus to a 1.0-cM interval.
      Comparison of the linkage map with physical maps of rat, mouse, and human refined
      the as critical region in a 2.2-Mb segment of the rat physical map between the
      D12Nas3 and D12Nas8 genes, which includes the Fkbp6 gene. A centromeric part of
      this segment corresponds to the region commonly deleted in Williams syndrome, a
      human complex developmental disorder, on human chromosome 7q11.23. The expression
      analysis of 23 genes located on the 2.2-Mb segments in various mouse tissues
      identified genes exclusively or strongly expressed in the testis.

PMID- 15516792
TI  - Disruption of the murine alpha1-antitrypsin/PI2 gene.
AB  - Alpha-1-antitrypsin (alpha1-AT) is a member of the serine protease inhibitor
      family regulating numerous proteolytic processes. The genetic disorder, alpha1-AT
      deficiency, is well known as a cause of hereditary pulmonary emphysema and liver
      cirrhosis. To create an animal model of human alpha1-AT deficiency, we disrupted
      the major murine isoform PI2, which is similar to human alpha1-AT and is one of 7
      alpha1-AT isoforms found in the mouse. The ability of the serum to inhibit the
      activities of human leukocyte elastase (HLE) and human chymotrypsin (CYT) was
      significantly lower in heterozygous mice (alpha1-AT/PI2 -/+) than wild-type
      (alpha1-AT/PI2 +/+) mice (73.2% vs. 100% for HLE and 67.8% vs.100% for CYT,
      respectively; P<0.05). The distribution of genotypes among F(2) progeny was not
      in accordance with Mendelian distribution (P<0.01), as the percentages of wild
      type, heterozygotes and homozygotes were 47.8%, 37.3% and 14.9%, respectively.
      Thus, it is likely that impairment of the protease inhibitor had a critical
      effect on fetus development. The alpha1-AT/PI2 deficient mouse will be a useful
      animal model for elucidating the function of alpha1-AT in fetal development,
      studying the mechanisms of chronic inflammatory disease and evaluating
      therapeutic candidates for the treatment of inflammatory disease.

PMID- 15516793
TI  - Effects of i.c.v. administration of leptin on copulatory and ingestive behavior
      in STZ-induced diabetic male rats.
AB  - It is well known that circulating leptin concentrations correlate with adiposity
      in both humans and rodents and decrease after fasting, energy restriction, or
      weight loss. The goal of the present study was to confirm whether the decreases
      of copulatory behavior and the increases of ingestive behavior in STZ-induced
      diabetic male rats could be reversed by i.c.v. administration of leptin. Adult
      male Wistar-Imamichi rats aged 9 weeks were used for the studies. Males received
      a single injection of STZ (60 mg/kg, i.p.) and vehicle. During the experiment,
      individual body weight, and food and water intake were measured. The copulatory
      and ingestive behaviors in STZ-induced diabetic males were observed at 2 and 4
      weeks after STZ. At 6 weeks after STZ, leptin (10 microg/10 microl) or aCSF
      (artificial cerebrospinal fluid) was injected through a lateral ventricle cannula
      and the above two behaviors were observed again. The i.c.v. leptin injection to
      STZ-induced diabetic males resulted in a significant increase of ejaculation
      frequencies (3.6 +/- 0.26 vs. 2.9 +/- 0.30 times) and a significant decrease in
      amount of food ingested (36.2 +/- 1.93 vs. 23.2 +/- 3.76 g), compared with the
      aCSF-injected control (p<0.01). These findings suggest that the copulatory and
      ingestive behaviors in i.c.v. leptin-injected STZ diabetic males were restored to
      levels equivalent to those in control males.

PMID- 15516794
TI  - Effect of six-and ten-day-old chick embryo amniotic fluid on development of two
      cell mouse embryos.
AB  - The purpose of this study was to investigate the effect of six-and ten-day-old
      chick embryo amniotic fluid (CEAF) on the development of two-cell mouse embryos.
      Six- and ten-day-old CEAF (6-AF, 10-AF) were aspirated separately from the
      amniotic cavity and two experiments were performed. In the first experiment, two
      cell mouse embryos were cultured in different supplements of heat-inactivated 6
      AF, pure heat-inactivated 6-AF and pure active 6-AF. The second experiment was
      also carried out in the same manner using the 10-AF. The rate of the development
      of embryos in all groups were daily determined and statistically compared with
      that of control (Ham's F-10 supplemented with 5 mg/ml human serum albumin).
      During the cultivation period, more embryos reached to the blastocyst stage in
      all groups of CEAF compared to the control. The result hatched blastocysts
      embryos also increased from days 3 till 5 of cultivation in all groups of CEAF.
      The developmental potential of embryos appears to be almost identical in six- and
      ten-day-old CEAF. In conclusion, CEAF as a supplement or a natural medium could
      support the development of two-cell mouse embryos.

PMID- 15516795
TI  - Role of IL-6 and IL-1beta in reactivation by acetylcholine of latently infecting
      pseudorabies virus.
AB  - We previously reported that the latently infecting Pseudorabies virus (PrV) could
      be reactivated by injection of swine or mice with acetylcholine. However, the
      mechanism of the reactivation was not clear yet. In this study, we analyzed the
      kinetics of cytokines related to stress to clarify the relationship between virus
      reactivation by acetylcholine and the immune system. IL-6 and IL-1beta were
      detected in mice after stimulation with acetylcholine. This shows that
      acetylcholine induced physiological stress conditions. However, there seemed to
      be no relationship between the kinetics of the cytokine levels and PrV excretion.
      Moreover, neither IL-6 nor IL-1beta alone could reactivate latently infecting
      PrV. Thus, acetylcholine causes the reactivation of latent PrV via a mechanism
      not involving these immunological factors.

PMID- 15516796
TI  - PCR method for genotyping and zygosity-testing of RasH2 transgenic mice.
AB  - In short-term carcinogenicity testing using CB6F1-TgrasH2 mice, sibling
      nonTgrasH2 mice are used as a negative control. However, selection of TgrasH2 and
      nonTgrasH2 mice has been performed by PCR with only transgene specific primers by
      the conventional method. Therefore, the conventional method involves the risk of
      false negative results due to reaction failure, and contamination with TgrasH2
      mice in the control mice group. Based on the nucleotide sequence information
      around the pre-integration site, we developed a genotyping method for
      distinguishing not only TgrasH2 mice (hemizygous for the Tg allele) but also
      nonTgrasH2 (homozygous for the nonTg allele) in a positive manner.

PMID- 15516797
TI  - Production of a cloned mouse by nuclear transfer from a fetal fibroblast cell of
      a mouse closed colony strain.
AB  - We have tested a closed colony mouse strain as a source for nuclei donors to
      determine differences in cloning efficiency. When donor nuclei were isolated from
      fetal fibroblast cells and injected into recipient oocytes from closed colony
      mice (ICR), reconstructed oocytes developed to full term and the success rate of
      cloning was 0.1%. This result indicates that cloning efficiency does not depend
      on the cell type. The body weight of the cloned mouse was lighter than controls,
      and the lifetime of the cloned mouse was the average for a mouse. These results
      contradict commonly-held views on cloning.

PMID- 15516798
TI  - Light-induced phase-shifting of the peripheral circadian oscillator in the hearts
      of food-deprived mice.
AB  - In the present study, we investigated the effect of fasting on photoentrainment
      of the peripheral circadian oscillator in the mammalian heart. Northern blotting
      showed that a single light pulse applied at an appropriate time in constant
      darkness, caused obvious phase-shifting in the circadian expression rhythm of the
      mammalian clock gene Period2 (mPer2) even in the hearts of food-deprived mice.
      Fasting did not significantly affect either the phase or the light-induced phase
      shifts of the mPer2 rhythm. Although several studies of temporal feeding
      restriction have indicated that feeding is the dominant timing cue for mammalian
      peripheral oscillators, our findings suggest that feeding is not essential for
      mammals to induce phase resetting of the circadian oscillator in the heart.

PMID- 15516799
TI  - Effective production of microinjectable blastocysts for germ-line transmission of
      embryonic stem cells.
AB  - Blastocysts of C57BL/6 mice obtained either 2.5 or 3.5 days post-coitum (dpc)
      were examined for efficient microinjection after overnight in vitro culture.
      Incidences of zona-free embryos were much higher at 3.5 dpc after natural mating
      (1.05/mouse) and superovulation (2.83/mouse) than at 2.5 dpc after natural mating
      (0.05/mouse) and superovulation (0.01/mouse). By testing germ-line competency of
      gene-targeted J1 embryonic stem cells, superovulation and/or in vitro culture
      should be recommended for producing microinjectable blastocysts for production of
      high germ-line chimeras.

PMID- 15516801
TI  - [Wilson's disease and its pharmacological treatment].
AB  - Wilson's disease is an inherited copper toxicosis caused by defective putative
      copper transporting ATPase in the liver. Because of impaired biliary secretion,
      copper remains in the liver, resulting in chronic hepatic lesions including fatty
      metamorphosis, chronic hepatitis and cirrhosis. In the latter stage,
      extrapyramidal syndromes may develop with and without symptomatic hepatic
      lesions. Acute liver damage associated with hemolysis and deep jaundice may be
      the first manifestation. The majority of patients show hypoceruloplasminemia,
      which has been used as a screening test for the disease. A large number of
      mutations in the ATP7B gene have been reported. Thus, genetic diagnosis might be
      limitedly used to presymptomatic diagnosis of siblings when mutations are
      identified in an index patient. Introduction of penicillamine caused a revolution
      in the treatment of patients. Another chelater, trientine, is now available for
      those intolerant of penicillamine. Tetrathiomolibdate and zinc acetate are
      additional alternatives currently being tested. Hypoceruloplasminemia and further
      reduction after chelation therapy may be associated with iron overload. This
      complication is closely related with impaired transport of ferrous ion due to
      ferroxidase deficiency. Noncompliance and teratogenicity are other major concerns
      because any treatment with the agents listed above is a life long regimen.
      Despite various side effects of penicillamine, its teratogenicity is negligible.
      These data indicate that penicillamine is the first choice of drug for this
      disease.

PMID- 15516802
TI  - [Synthesis of phosphonic acid and phosphinic acid derivatives for development of
      biologically active compounds].
AB  - This paper covers recent publications from our laboratory on the synthesis of a
      variety of phosphonate and phosphinate derivatives. New methods for the
      enantioselective synthesis of alpha-hydroxyphosphonates were established by Lewis
      acid-mediated cleavage of homochiral 1,3-dioxaneacetals with P(OEt)(3) and chiral
      metal ligand-mediated hydrophosphonylation of aldehydes. Two diastereomers of
      HPmp derivatives were prepared by an application of these methods. The HPmp
      derivatives were convered to FPmp derivatives but with low diastereoselectivity.
      Hydrophosphonylation of alpha-aminoaldehydes afforded threo- and erythro-beta
      amino-alpha-hydroxyphosphonates under chelation and nonchelation controlled
      conditions, respectively. The asymmetric dihydroxylation of alpha, beta-, and
      beta, gamma-unsaturated phosphonates with AD-mix-alpha and AD-mix-beta reagents
      gave alpha, beta- and beta, gamma-dihydroxyphosphonates with high
      enantioselectivity. The method was applied to the kinetic resolution of racemic
      alpha-oxygetated beta, gamma-unsaturated phosphonates. Treatment of
      allyloxymethylphosphonates with the base afforded alpha-hydroxyphosphonates via
      the [2,3]-Wittig reaction. Threo- and erythro-beta-amino-alpha
      hydroxyphosphinates were obtained with high diastereoselectivity by
      phosphinylation of alpha-aminoaldehydes in the presence of (R)- and (S)-ALB,
      respectively. The phosphinylation of alpha-oxygenated aldehydes afforded the
      corresponding alpha, beta-dioxygenated phosphinates, but with low
      diastereoselectivity. Sphingomyelin analogues containing CF(2)PO(OH)(2) were
      synthesized starting from (S)- and (R)-Garner aldehyde for the purpose of
      obtaining potent sphyngomyelinase inhibitors. A useful method for the synthesis
      of alpha, alpha-difluorobenzylphosphonates was established based on the cross
      coupling reaction of an iodobenzene derivative with ZnCuBr(2)CF(2)PO(OEt)(2). The
      synthetic utility of ZnCuBr(2)CF(2)PO(OEt)(2) was examined to obtain alpha, alpha
      difluoromethylenenphosphonates. The method was applied to a synthesis of PNP
      inhibitory active compounds by combination of the purine base and alcohols
      containing difluoromethylenephosphonate. The methodology for the beta-selective N
      glycosylation of 2,3-dideoxy glucoside was established by introducing
      phosphonothioates at the 3-position of glycosyl doners instead of phosphonate.
      Synthesis of new acylic nucleotide analogues designed based on the structural
      modification of ARS2267 is also described. Finally, kiral synthesis of some
      phosphonates was achieved using lipase through kinetic resolution.

PMID- 15516803
TI  - [X-ray crystallographic analysis of picrates].
AB  - Picric acid forms stable picrates with various organic molecules through pi-
      bonding or ionic bonding, and such picrates have been very useful for
      identification and qualitative analysis. As it seemed desirable to determine the
      crystal structures and the bonding mode of picrates of basic organic compounds,
      we have investigated the crystal structures of aromatic hydrocarbons, aromatic
      amino compounds, heterocyclic compounds and so on. A series of our studies on the
      crystal structure of basic organic compounds have shown that the complexes of
      picric acid and aromatic hydrocarbons are formed through pi-bonding, and those of
      aromatic heterocyclic compounds are formed through ionic and hydrogen bonding; in
      addition, some of them also have pi-bonding.

PMID- 15516804
TI  - [Development of novel DDS technologies for pharmacoproteomic-based drug discovery
      and development].
AB  - With the success of the Human Genome Project, the focus of life science research
      has shifted to the functional and structural analyses of proteins, such as
      proteomics and structural genomics. These novel approaches to the analysis of
      proteins, including newly identified ones, are expected to help in the
      identification and development of protein therapies for various diseases. Thus
      pharmacoproteomic-based drug discovery currently has a very high profile.
      Nevertheless, the use of bioactive proteins in the clinical setting is not
      straightforward because in vivo these proteins have low stability and pleiotropic
      action. To promote pharmacoproteomic-based drug discovery and development, we
      have attempted to establish a system for creating functional mutant proteins
      (muteins) with the desired properties and to develop a site-specific
      bioconjugation system for further improving their therapeutic potency. These
      innovative protein-drug systems are discussed in this review.

PMID- 15516805
TI  - [Bridged nucleic acids (BNAs) as a basic material for genome technology].
AB  - The completion of the human genome sequencing project will greatly accelerate the
      development of novel and practical technologies for genome-analysis, diagnostics
      or therapeutics. Oligonucleotides are playing an important role in these genome
      technologies, because of their sequence-specific hybridization ability toward the
      complementary strand. Besides the sequence-specific duplex formation,
      oligonucleotides are able to form stable triplex structures, which is fundamental
      to the antigene strategy to regulate gene expression in a living cell. However,
      two major drawbacks are known in the triplex formation by a natural
      oligonucleotide: low stability of the triplex and limitations of the target DNA
      sequence. One promising strategy to overcome these problems is chemical
      modification of the oligonucleotides. We have developed various bridged nucleic
      acids (BNAs), and found that the oligonucleotides containing 2'-O,4'-C-methylene
      bridged nucleic acid (2',4'-BNA) modification form a stable parallel motif
      triplex with the double-stranded DNA target under physiological conditions. Some
      nucleobase analogues to extend the target DNA sequence were designed, synthesized
      and incorporated into the 2',4'-BNA structure. The obtained 2',4'-BNA derivatives
      containing modified nucleobases effectively recognized a pyrimidine-purine
      interruption. Some other examples of nucleic acid analogues to overcome the two
      major drawbacks in the triplex-forming oligonucleotides are also summarized.

PMID- 15516806
TI  - [Physiological function of blood-brain barrier transporters as the CNS supporting
      and protecting system].
AB  - The blood-brain barrier (BBB) segregates the circulating blood from interstitial
      fluid in the brain and restricts drug permeability into the brain. Our latest
      studies have revealed that the BBB transporters play important physiological
      roles in maintaining the brain environment. For an energy-storing system, the
      creatine transporter localized at the brain capillary endothelial cells (BCECs)
      mediates the supply of creatine from the blood to the brain. The BBB is involved
      in the brain-to-blood efflux transport of gamma-aminobutyric acid, and GAT2/BGT-1
      mediates this transport process. BCECs also express serotonin and norepinephrine
      transporters. Organic anion transporter 3 (OAT3) and ASCT2 are localized at the
      abluminal membrane of the BCECs. OAT3 is involved in the brain-to-blood efflux of
      a dopamine metabolite, a uremic toxin, and thiopurine nucleobase analogues. ASCT2
      plays a role in L-isomer-selective aspartic acid efflux transport at the BBB.
      Dehydroepiandrosterone sulfate and small neutral amino acids undergo brain-to
      blood efflux transport mediated by organic anion transporting polypeptide 2 and
      ATA2, respectively. The BBB transporters are regulated by various factors: ATA2
      by osmolarity, taurine transporter by tumor necrosis factor-alpha, and L
      cystine/L-glutamic acid exchange transporter by oxidative stress. Clarifying the
      physiological roles of BBB transport systems should give important information
      allowing the development of better central nervous system (CNS) drugs and
      improving our understanding of the relationship between CNS disorders and BBB
      function.

PMID- 15516807
TI  - [Design and synthesis of subtype- and species-selective peroxisome proliferator
      activated receptor (PPAR) alpha ligands].
AB  - The molecular pharmacological discovery of the nuclear receptor peroxisome
      proliferator-activated receptor alpha (PPAR alpha) as the master regulator of
      lipid and lipoprotein homeostasis, and the rapid development of a parallel
      screening approach to evaluate activity towards other PPAR subtypes (PPAR delta,
      and PPAR gamma) have provided an opportunity to develop novel PPAR alpha
      selective, PPAR alpha/gamma dual, and PPAR pan agonists. This review focuses on
      the molecular pharmacology of PPAR alpha, and summarizes our current design,
      synthesis, and evaluation of subtype-selective PPAR alpha agonists. The species
      selectivity of several classes of PPAR alpha selective agonists in response to in
      vitro PPAR alpha transactivation activity is also reported. These studies should
      help us to understand the structure-activity relationships and the mode of
      interaction between ligands and PPAR alpha, and also help to create novel
      therapeutic choices for the treatment of metabolic disorders.

PMID- 15516808
TI  - [Comparison of the effects of prophylactic antibiotic therapy and cost
      effectiveness between cefazolin (CEZ) and Sulbactam/Ampicillin (SBT/ABPC) in
      gastric cancer surgery employing clinical pathway].
AB  - The present study was designed to investigate the effects of prophylactic
      antibiotic therapy and the cost-effectiveness of Cefazolin (CEZ) and
      Sulbactam/Ampicillin (SBT/ABPC) in gastric cancer surgery employing clinical
      pathway. 157 patients (62 in the CEZ group and 95 in the SBT/ABPC group), who
      underwent surgery for gastric cancer at the First Department of Surgery of our
      hospital, were investigated. There was no significant difference between the
      groups with regard to sex, age, incidence of complication, stage of cancer,
      surgical method, operative time and blood loss, length of hospitalization, the
      appearance of systemic inflammatory response syndrome (SIRS), changes body
      temperature, white blood cell count (WBC), C-reactive protein (CRP), or clinical
      outcome of postoperative care by a nurse during post-operation for 7 days. The
      prophylactic effect of infection was also no different between the CEZ (69.4%)
      and SBT/ABPC (69.5%) groups. In contrast, decision analysis strongly indicated
      that the anticipate cost of antibiotics was higher in the latter group (yen
      20402) than in the CEZ group (yen 15556), suggesting that the prophylactic effect
      of CEZ may be more cost-effective. Thus, evaluations of pharmacotherapy from the
      aspect of cost may be one of the important responsibility of hospital pharmacists
      in the future.

PMID- 15516809
TI  - Beta-adrenergic blocking agents and intermittent claudication: systematic review.
AB  - To clarify contradictions in past reports and the package inserts for beta
      adrenergic blocking agents (beta-blockers) for patients with intermittent
      claudication (IC), we investigated the effects of beta-blockers in patients with
      IC using the systematic review technique. Data sources were randomized,
      controlled trials that investigated the effects of beta-blockers compared with
      the placebo or untreated group (controls) in patients with IC. Primary endpoints
      were walking distance and walking time, and secondary endpoints were ankle
      brachial index (ABI) and calf blood flow. Nine trials were included in the
      analysis. Meta-analysis showed that there was a significant worsening in maximal
      walking distance and initial claudication distance in patients receiving beta
      blockers, with standardized mean differences of -0.31 and -0.39 (95% confidence
      interval -0.58 to -0.04 and -0.73 to -0.06, P=0.03 and 0.02, respectively)
      compared with controls. There were no significant differences in maximal walking
      time (0.07, -0.24 to 0.37), time to onset of claudication (0.12, -0.23 to 0.47),
      ABI at rest (0.24, -0.30 to 0.78), calf blood flow at rest (0.00, -0.26 to 0.25),
      and calf blood flow after exercise (-0.23, -0.69 to 0.22). However, only one
      trial evaluated ABI, and the number of cases is increasing, suggesting that beta
      blockers do not worsen ABI. There was no evidence that beta-blockers prescribed
      for patients with IC have unsuitable "precautions" in the package inserts.
      However, reluctance to administer beta-blockers to patients because they have IC
      is not appropriate.

PMID- 15516810
TI  - [Pharmaceutical and pharmacological evaluation of Burow's solution (aluminum
      acetate solution), hospital preparation, and development of its rapid preparation
      method].
AB  - Burow's solution, or aluminum acetate solution, is effective in inhibiting
      various microorganisms including methicillin-resistant Staphylococcus aureus
      (MRSA) that are commonly observed in chronic suppurative otitis media. It takes
      several days to prepare Burow's solution using aluminum sulfate, and the
      pharmaceutical properties of the solution are not fully understood. In this
      study, the effect of storage (5 months) of Burow's solution prepared according to
      the Teine-Keijin Hospital manual on its pharmaceutical properties and
      antibacterial activities was examined. We also attempted to develop a rapid
      preparation method of aluminum acetate (or 1.7% aluminum) solution using two
      commercially available compounds of aluminum acetate basic
      (Al(2)O(CH(3)CO(2))(4), Al(OH)(CH(3)CO(2))(2)). The properties of Burow's
      solution, pH, osmolarity and antibacterial activity, were the same among
      different preparations and its storage for 5 months at 4 degrees C had no effect
      on these properties. The antibacterial potency of Burow's solution was dependent
      on aluminum concentration and its antibacterial potency against S. aureus and
      several MRSA strains was of the same magnitude. In a rapid preparation, aluminum
      acetate basic was mixed with appropriate amounts of tartaric acid and acetic
      acid, and the suspension was boiled for 2-2.5 hr until dissolved. The rapidly
      prepared aluminum acetate solution showed the same pharmaceutical properties and
      antibacterial activities as those of Burow's solution. The newly developed
      preparation method for aluminum acetate solution is expected to be convenient and
      feasible for hospital treatment of chronic suppurative otitis media.

PMID- 15516811
TI  - [Effects of long-term administration of caffeine on fat storage in ovariectomized
      rats].
AB  - It is well known that obesity occurs in women with climacteric disorders. The aim
      of this study was to examine whether caffeine prevents obesity and bone loss in
      ovariectomized rats (ovx). Eight-week-old female Wistar rat were assigned to 4
      groups: a sham-operated group fed the control diet (CE-2); an ovx-c group fed the
      control diet; an ovx-caf 0.15% group fed the control diet containing 1.5 g/kg of
      caffeine; and an ovx-caf 0.3% group fed the control diet containing 3 g/kg of
      caffeine. Body weights at 2-9 weeks and the final parametrail adipose tissue
      weights were significantly lower in the ovx-caf 0.3% group than in the ovx-c
      group. Food intakes were significantly lower in the ovx-caf 0.3% group than in
      the ovx-c group. After 9 weeks, the rats were killed and adipose tissues were
      sampled immediately. Basal lipolysis was increased in the ovx-caf 0.3% group fed
      the control diet containing 3 g/kg of caffeine than in the ovx-c group fed the
      control diet. The relative content of calcium (g/100 g body weight) in the ovx
      caf 0.3% group was significantly increased compared with that in the ovx-c group.
      These results show a new possible role for caffeine in the prevention of
      lifestyle-related diseases.

PMID- 15516812
TI  - [Assessment of antioxidant activity of natural compound by water- and lipid
      soluble antioxidant factor].
AB  - We evaluated the antioxidant activity of natural compounds in water-soluble and
      lipid-soluble phases and found that ferulic acid, quercetin and caffeic acid
      showed stronger activity in the water-soluble phase. Various fractions isolated
      from Bidens pilosa showed this activity mainly in the water-soluble phase.
      Antioxidant activity in the lipid-soluble phase of propolis depended on the
      lipophilic extraction.

PMID- 15516813
TI  - [Studies on antihypertensive effect of Luobuma (Apocynum venetum L.) leaf extract
      (3)].
AB  - To clarify the mechanisms underlying the antihypertensive effect of Luobuma
      (Apocynum venetum L. (Apocynaceae)) leaf extract (LLE), we investigated the
      vasodilator effect of LLE in the rat mesenteric vascular bed, which plays an
      important role in changes in peripheral resistance and thus the regulation of
      blood pressure. In the perfused mesenteric vascular bed with active tone and
      intact endothelium, perfusion of LLE (0.1 ng to 100 mg/ml for 15 min) caused dose
      dependent vasodilation, which was abolished by chemical removal of the
      endothelial layer with perfusion of sodium deoxycholate, but not by N(G)-nitro-L
      arginine-methyl ester (L-NAME), a competitive inhibitor of nitric oxide (NO),
      which instead increased the effect. The LLE-induced vasodilation was partially
      inhibited by high K(+)-containing Krebs solution and tetraethylammonium (a K(+)
      channel blocker) and completely by the combination of L-NAME and high K(+)-Krebs
      solution. However, atropine (a muscarinic acetylcholine receptor antagonist) did
      not affect the vasodilation. These results suggest that the vasodilation induced
      by LLE is endothelium-dependent and mediated by endothelium-derived
      hyperpolarizing factor, which involves the activation of K(+)-channels. The
      higher concentrations of LLE may enhance NO production/release to cause
      vasodilation.

PMID- 15516814
TI  - [Pancreaticojejunal anastomosis: the "Achilles heel" of pancreaticoduodenectomy].
AB  - This article reviews available data on factors influencing healing of pancreatic
      anastomosis following pancreaticoduodenectomy. Technical approaches of various
      techniques of pancreatic anastomosis including pancreaticogastrostomy are
      discussed and compared. Attention is paid to the other associated risk factors
      for pancreatic anastomotic leakage such as patient status, as well as morphologic
      and physiologic peculiarities of pancreatic remnant. The concept of
      pharmacological prevention of anastomotic leakage is discussed.

PMID- 15516815
TI  - Gender differences of sodium metabolism and hyponatremia as an adverse drug
      effect.
AB  - Gender-related differences in sodium (Na+) metabolism, Na+ transport through cell
      membrane, intracellular Na+ concentration, and Na+ urinary excretion review is
      presented in the article. Literature data on gender-related differences in the
      occurrence of hyponatremia and related neurology are overviewed. Some of the
      drugs used in neurology (carbamazepine, oxcarbazepine, thiazides,
      antidepressants) are pointed out as eventual sources of hyponatremia. This
      disorder shows a clear-cut preference of the feminine gender. The authors present
      literature data on gender-related differences in the mechanisms of Na+ transport
      (Na+/H+ exchange, Na+/K+/2Cl- cotransport, Na+, K+-ATPase). The reasons for such
      differences are not yet known. Investigative tests with animals of both genders,
      cellular studies and clinical investigations with human males and females could
      help to answer question why females are more prone to hyponatremia, to select
      more efficient measures for prevention of hyponatremia and to differentiate
      specific peculiarities of treatment for patients of either sex.

PMID- 15516816
TI  - [Peculiarities of the investigation, clinics and treatment of stylohyoid syndrome
      and glossopharyngeal neuropathy].
AB  - The aim of the study was to investigate the causes and the clinics of stylohyoid
      syndrome and its tendency to convert into glossopharyngeal nerve neuropathy; to
      investigate clinical peculiarities of glossopharyngeal neuropathy; to estimate
      differential diagnosis criteria for the glossopharyngeal neuropathy and
      stylohyoid syndrome; as well as to propose optimal treatment of the neuropathy.
      MATERIAL AND METHODS: Sixty-five patients with stylohyoid syndrome and 53
      patients with glossopharyngeal neuropathy have been treated on. The diagnosis was
      estimated according to the data of clinical and X-ray investigation. For the
      localization of affected zone we performed modified facial straight plain
      radiograms of the patients in open bite position, facial oblique contact
      radiograms, orthopantomograms and cervical spondylograms. RESULTS: The majority
      of the patients were females; they comprised 61.5% of patients with stylohyoid
      syndrome and 56.6% of glossopharyngeal neuropathy sufferers. Older persons had
      neuropathy, younger--stylohyoid syndrome. The mean age of neuropathy patients was
      63.8 years, and of stylohyoid syndrome--57.1 years. Seven years and longer
      duration of disease was observed in 73.3% of glossopharyngeal neuropathy
      patients, while duration of 7 and more years was observed in only 3.1% of
      stylohyoid syndrome patients. The mean duration of glossopharyngeal neuropathy
      was 10.9 years, and of stylohyoid syndrome--2.6 years. The analysis of
      etiological factors showed they are the same for both diseases. CONCLUSIONS: The
      core of the glossopharyngeal neuropathy pathogenesis is destruction at the
      glossopharyngeal nerve or at the perivascular plexus of carotid artery, because
      of elongation or dislocation of styloid processus in case of neck osteochondrosis
      and compression by ossified styloid ligament. In case of stylohyoid syndrome,
      inflammatory processes occur at the above-mentioned nervous elements.

PMID- 15516817
TI  - Brain natriuretic peptide and other cardiac markers in predicting left
      ventricular remodeling in patients with the first myocardial infarction.
AB  - Left ventricular remodeling is a complex pathologic process of progressive
      dilatation, leading to dysfunction and heart failure in patients with acute
      myocardial infarction. The aim of our study was to determine and evaluate
      biochemical markers, reflecting cardiac remodeling process in the patients with
      the first myocardial infarction and to compare those markers with clinical
      characteristics of left ventricular remodeling. MATERIAL AND METHODS:
      Concentrations of brain natriuretic peptide and markers of myocardial necrosis
      were measured on 1st , 2nd and 7th day after the onset of the first acute
      myocardial infarction, as well as after 3 and 6 months in 30 patients. Parameters
      of left ventricular remodeling were determined by echocardiographic
      investigation, which was performed in the acute phase and after 3 and 6 months.
      RESULTS: Brain natriuretic peptide concentration was found to be related to the
      left ventricular geometry in the acute phase: brain natriuretic peptide peak
      level was lower in the patients with the normal left ventricular geometry than in
      the patients with the changed left ventricular geometry (140.6+/-63.3 pg/ml vs.
      385.7+/-283.9, p<0.05). Brain natriuretic peptide concentration in the acute
      phase was higher in the patients who had increased left ventricular end diastolic
      diameter through 6-month period (348.9+/-309.4 pg/ml vs. 145.1+/-109.6 pg/ml,
      p<0.05). Higher troponin I (58.8+/-33.6 ng/ml vs. 30.9+/-31.3 ng/ml, p<0.05) and
      troponin T (4.5+/-2.2 ng/ml vs. 1.9+/-2.0 ng/ml, p<0.05) levels were also
      associated with left ventricular dilatation through 6 months after myocardial
      infarction. CONCLUSIONS: Brain natriuretic peptide level in acute phase of
      myocardial infarction is related to the left ventricular geometry changes and
      remodeling. Brain natriuretic peptide together with other cardiac markers might
      be useful in predicting subsequent cardiac function.

PMID- 15516818
TI  - Influence of enteral nutrition on the frequency of complications in case of major
      burns.
AB  - The objective of the study was to assess if enteral nutrition reduces the rate of
      severe complications and complication-related mortality in case of major burns.
      MATERIAL AND METHODS: Two groups were included in the study. Group A was assessed
      prospectively and included 67 patients treated in Kaunas University of Medicine
      Hospital in 2000-2003. These patients received 30-40 kcal/kg/day in enteral way
      over the period of wound surgery. Group A was compared with Group B, which was
      assessed retrospectively and included 71 patients without enteral nutrition
      treated in 1997-1998. Groups were homogeneous by patients' age; extent of general
      and deep burn area; Baux and Burn indexes. RESULTS: 10 patients (15%) in Group A
      had pneumonia, 3 (30%) of them died; 11 (16%) had lung edema, 3 (27%) of them
      died; 24 (36%) had sepsis, 3 (12.5%) of them died; renal insufficiency was
      diagnosed to 4 patients (6%) in Group A, 2 (50%) of them died. In Group B
      (without enteral nutrition) pneumonia was diagnosed to 27 patients (38%) of 71,
      18 (63%) of them died; lung edema--to 20 (28%), 18 (90%) of them died, 19
      patients (27%) had sepsis, 12 (63%) of them died; renal insufficiency was
      diagnosed to 10 patients (14%), all of them (100%) died. CONCLUSIONS: Enteral
      nutrition statistically significantly diminished frequency of pneumonia and lung
      edema for burned patients. Pneumonia, lung edema, sepsis and renal insufficiency
      were less hazardous for life of patients with enteral nutrition (p<0.05).

PMID- 15516819
TI  - Improvement of liver histopathology in patients with hepatitis C after interferon
      and ribavirin combination therapy.
AB  - Aim of the study was to evaluate the effect of interferon and ribavirin
      combination therapy on liver histopathological outcomes. MATERIAL AND METHODS:
      Pre-treatment and post 24-week treatment liver biopsy specimens were available in
      68 naive patients, 37 nonresponders and 18 relapsers after interferon
      monotherapy. For all patients paired liver biopsies (6-month interval) were
      assessed for necroinflammation (according to the method by K. Ishak), fibrosis
      (according to METAVIR score) and steatosis at the end of 24-week treatment.
      RESULTS: Virological end-of-treatment response was: 36.8% in naive patients,
      24.3% in nonresponders and 22.2% in relapsers. Out of 38 patients, who achieved
      virological end-of-treatment response, sustained virological response was in
      65.8%. There was obvious drop of histological activity features scores in all
      treated patients at the end of 24-week treatment period. According to the
      baseline findings, only confluent necrosis was found to be significantly lower in
      patients, who achieved virological end-of- treatment response (p<0.05). The
      fibrosis and steatosis has not been influenced at least by 24-week treatment
      success. But in patients, who achieved sustained virological response, fibrosis
      was lower at baseline and after 24-week of interferon and ribavirin therapy
      (p<0.001). In conclusion, assessment of liver histopathology has real value in
      the evaluation of therapeutic response. Grade of pre-treatment confluent necrosis
      could predict virological end-of-treatment response. Lower stage of fibrosis both
      at baseline and after 24-week treatment period seems to be a predictor of
      sustained virological response.

PMID- 15516820
TI  - [Primary peritonitis caused by group A beta-hemolytic streptococcus].
AB  - A rare case of primary peritonitis caused by group A beta-hemolytic streptococcus
      in previously healthy woman is presented. The entry site of infection was
      tonsillitis. Infection was complicated by soft-tissue infection of abdominal and
      thoracic wall, associated with toxic shock. Streptococcus growth was obtained in
      the cultures from the tonsils and blood. The patient underwent surgery:
      laparoscopy, laparotomy and multiple incisions in the phlegmon site. The lasting
      administration of penicillin caused recovery.

PMID- 15516821
TI  - [Quantitative analysis of active substances in St. John's wort (Hypericum
      perforatum L.) by the high performance liquid chromatography method].
AB  - The flavonoids (rutin, quercetin, and isoquercetin) and hypericin are the main
      active substances of St. John's wort (Hypericum perforatum). They support
      regeneration of human body cells, provide disinfection, and act as
      antidepressant, antiviral, and anti-inflammation tools. Such large spectrum of
      the applicable functions depends on the quantity of each substance. The objective
      of this paper is to determine the regularities of the quantitative variation of
      rutin, quercetin, isoquercetin and hypericin in flowers and leaves of St. John's
      wort in different habitats and different plant development phases. Plant material
      for the quantitative analysis was collected in 1998-1999. The high performance
      liquid chromatography (HPLC) was applied for the quantitative analysis of the
      active substances in St. John's wort. The flavonoids (rutin, quercetin, and
      isoquercetin) were identified under the UV waves of 254 nm, and hypericin - under
      the waves of 590 nm. Larger quantities of rutin were found in leaves, while those
      of quercetin, isoquercetin and hypericin - in flowers of St. John's wort. The
      highest accumulation of active substances was observed during the development of
      flowering buds and in flowering time. The quantitative variation of active
      substances in different habitats allows the selection of the best plant samples
      for their cultivation and conservation in field collections.

PMID- 15516822
TI  - The effects of zinc ions on activities of tRNALeu and leucyl-tRNA synthetase of
      mice liver.
AB  - The aim of this study was to examine the effects of zinc ions on activities of
      tRNA(Leu) and leucyl-tRNA synthetase of mice liver. MATERIAL AND METHODS: White
      laboratory mice (20-25 g) were used for study purposes. Animals were intoxicated
      with ions of zinc by injection of 0.15 LD50 dose of zinc sulphate solution (1.56
      mg Zn2+ per 1 kg of body weight) into abdominal cavity. After 8 hours,
      preparations of total tRNA and aminoacyl-tRNA synthetases were isolated from the
      intoxicated and normal (control) mice liver. Acceptor activity of tRNA(Leu) and
      activity of leucyl-tRNA synthetase were determined in tRNA aminoacylation
      reaction using [14C]-labeled leucine. Actions of zinc ions on acceptor activity
      of tRNA(Leu) and on activity of leucyl-tRNA synthetase from liver of control
      animals in vitro were determined after addition into reaction mixture different
      concentrations of zinc sulphate solution. RESULTS: It was determined that
      acceptor activity of mice liver tRNA( Leu)8 hours after intoxication with zinc
      ions has increased by 29% and activity of leucyl-tRNA synthetase has increased by
      20% as compared to control. Experiments in vitro have shown that 5-20 microM
      concentrations of zinc ions in reaction mixture stimulate the acceptor activity
      of mice liver tRNA(Leu)by 18-30%, higher concentration of zinc ions (40 microM)-
      suppresses it by 26%. The study of leucyl-tRNA synthetase activity in vitro has
      shown that 5-10 microM concentrations of zinc ions in reaction mixture increase
      activity of this enzyme by 11-16%, higher concentrations of zinc ions (20-40
      microM)--decrease it by 13-21%. CONCLUSIONS: After 8-hour intoxication with zinc
      ions the activities of both studied components of the translation machinery-
      tRNA(Leu) and leucyl-tRNA synthetase were increased. It may be connected with the
      stimulation of zinc-binding metallothionein synthesis which is involved in the
      detoxification of heavy metals. Low concentrations of zinc ions in reaction
      mixture increase tRNA(Leu) and leucyl-tRNA synthetase activities; higher
      concentrations of these ions decrease activity of those components of protein
      synthesis system. The results show that zinc ions directly act on the activities
      of both components of translation machinery.

PMID- 15516823
TI  - The influence of hypodynamic stress on ultrastructure of the cortical layer cells
      of eye lens.
AB  - The aim of the study was to determine the influence of 48-day hypodynamic stress
      on the ultrastructure of the cortical layer cells of eye lens. Hypodynamic stress
      was induced in Chinchilla male rabbits (weight 2.5-3.0 kg; n=8) by placing them
      in metal hutches for 48 days. Rabbits (n=8) of the control group (non-stressed)
      were kept under normal vivarium conditions. Following the hypodynamic regime
      (after 48 days) the rabbits (stressed and control) were anaesthetized using
      thiopental sodium (35 mg/kg). On removing their eyes, the cortical partes of
      lenses were prepared and immersed into a fixative solution containing 2%
      paraformaldehyde and 2.5% glutaraldehyde in 0.1 M cacodylate buffer (pH 7.4) for
      more than 4 hours at room temperature or overnight at 4 degrees C. The specimens
      were then postfixed, dehydrated and embedded in a mixture of Epon 812 and
      Araldite. Ultrathin sections stained with uranyl acetate and lead citrate were
      evaluated by electron microscopy (Philips-300). Microscopical examination of the
      cortical layer cells of lenses showed extensive cellular vacuolization,
      calcification, and formation of a light scattering center. Cortical fibers were
      found to be compacted along their length, and elongated with decreased
      interdigitations.

PMID- 15516824
TI  - Effect of Polyscias filicifolia Bailey biomass on protein synthesis process in
      isolated pig heart.
AB  - OBJECTIVE: The aim of this study was to investigate effect of Polyscias
      filicifolia Bailey biomass on protein synthesis process in normoxic and anoxic
      pig heart. MATERIAL AND METHODS: Experiments were done on isolated pig hearts
      weighing 100-150 g. Effects of anoxia were evaluated after 20 and 90 min of
      anoxic perfusion. Control hearts were perfused under aerobic conditions.
      Investigating action of Polyscias filicifolia Bailey, pig heart was perfused
      under normoxic and anoxic condition with buffer, which contains tincture
      Polyscias filicifolia Bailey. For the determination of protein synthesis rate
      (time of incubation was 15 min) and level (time of incubation was 60 min),
      incorporation of [14C]-leucine into translational products in a cell-free system
      was measured. RESULTS: Protein synthesis rate and level in cell-free system
      decreased by 30% and 20% respectively after 20 min anoxic perfusion and by 48%
      and 45% respectively after 90 min anoxic perfusion in comparison to the control.
      Polyscias filicifolia Bailey tincture did not affect the protein synthesis rate
      and level in cell-free translation system from control pig heart. Polyscias
      filicifolia Bailey tincture has protective effect on protein synthesis system
      from pig hearts after 20 min and 90 min anoxic perfusion. Protein synthesis rate
      and level after 20 min anoxic perfusion with Polyscias filicifolia Bailey
      tincture was the same as at a control level. However, after 90 min anoxic
      perfusion with Polyscias filicifolia Bailey tincture protein synthesis rate and
      level did not reach control level and represented 81% and 76% respectively of
      control values. Spectrum of newly synthesized polypeptides in cell-free protein
      synthesis system under anoxic conditions and after treatment with Polyscias
      filicifolia Bailey tincture did not differ. CONCLUSIONS: Protein synthesis rate
      and level decreased under long and short-term anoxia. Polyscias filicifolia
      Bailey biomass restore protein synthesis system under anoxia. Neither anoxia, nor
      Polyscias filicifolia Bailey tincture did not influence spectrum of newly
      synthesized proteins.

PMID- 15516825
TI  - [Use of contraceptives among adolescent girls and its relation with the Chlamydia
      trachomatis infection].
AB  - OBJECTIVES: Study aimed to evaluate the age of early sexual intercourse of
      adolescent girls and peculiarities of use of contraceptives. Establishing the
      risk factors for Chlamydia trachomatis infection was one of study objectives.
      MATERIAL AND METHODS: The "Questionnaire on Sexual Health Behavior" was developed
      by the authors. Anonymous questionnaire survey was conducted among 487 adolescent
      girls aged 15-19 years at vocational training schools and general education
      secondary schools in Kaunas. RESULTS: Out of the respondent girls, 29.9% were
      exposed for the sexual intercourse at the age of 15 years or earlier. Only 30.0%
      of adolescent girls reported use of contraceptives during their last sexual
      intercourse. Majority of respondent girls has reported use of condoms (87.7%).
      One third of respondents (33.1%) used method of interrupted sexual intercourse,
      22.3% used hormonal contraceptive pills, 13.0% reported use the method of
      calculation of fertility days, and 6.5%--local chemical contraceptives.
      CONCLUSIONS: It was established that significant part of adolescent girls have
      had their first sexual intercourse before age of 15 years. Adolescent girls have
      indicated poor knowledge and irregular use of contraceptives. Respondent girls,
      who were infected by Chlamydia trachomatis reported poor attitudes and knowledge
      concerning the risky sexual behavior.

PMID- 15516826
TI  - Evaluating average expenditures per case in Kaunas University of Medicine
      Hospital.
AB  - The aim of the study was to evaluate average expenditures per case in Kaunas
      University of Medicine Hospital (KUMH). Case is defined as one treatment episode
      in particular inpatient department. Five cost groups have been used and defined
      in monetary terms in each clinical category (profile): labor costs; medication
      costs; laboratory, radiology and anesthesiology (for surgical clinics) services
      costs; running costs of medical equipment supply; other costs (including costs of
      patients' meal, laundry, transportation, communication, auxiliary services,
      heating, electricity, water, buildings maintenance and repair, etc.). Cases were
      analyzed using case mix dimensions: gender, age, absence or presence of surgical
      operation, patient separation status and inpatient service groups. During the
      study average expenditures per case were estimated: surgery--1161.10 Litas,
      therapy--1312.15 Litas, obstetrics and gynecology--685.82 Litas, newborn and
      child care--893.54 Litas and intensive care--1292.92 Litas. Relation between
      expenditures and case mix variables was measured using correlation analysis
      method. Using multiple regression analysis method, expenditures per case in each
      clinical category (profile), according case mix dimensions were predicted.
      Predicted expenses did not differ much from estimated cost per case.

PMID- 15516827
TI  - Do age, gender and marital status influence job strain development for general
      practitioner?
AB  - BACKGROUND: General practice is one of the most stressful workplaces among health
      care workers and is characterized by higher rates of job strain than in reference
      population. We need to take into account that respondents are influenced by quite
      similar working conditions and health status differently. Thus this article aimed
      to review the subjective processes, which make general practitioners more
      vulnerable to the job strain. METHODS: Computerized database Medline was
      searched. Search included data for 1983-2003. In this review data form many
      comparative cross-sectional studies found in this database were included. A data
      collection form was developed, prepared and filled up on reading each article.
      RESULTS: Collected studies highlighted that age, gender and marital status
      influence job strain development for general practitioner but were very
      controversial on how and whom they influence. We found that outcomes of job
      strain have higher impact for females than for males. We also found data that
      males have also high rates of job strain working in general practice. The age
      impact on job strain between females and males increases in older age groups. The
      rate of job strain is the highest among middle-aged general practitioners and
      depends on marital status. Married females have the worst health and are most
      vulnerable to job strain. CONCLUSIONS: Magnitude of job strain varies depending
      on age, gender and marital status of general practitioner. The highest rates of
      job strain are mostly observed in married females, younger or older general
      practitioners. Sociodemographic factors contribute to this. The development of
      job strain, in some extent, can be explained within social context.

PMID- 15516828
TI  - [Pulmonary hypertension: the issues of diagnosis and treatment].
AB  - Pulmonary hypertension is not a rare pathology that is met in a doctor's
      practice. It has been defined as a mean pulmonary artery pressure >25 mmHg at
      rest or >30 mmHg at exercise, or by a systolic pulmonary artery pressure >40 mmHg
      measured by echo-Doppler. The article analyzes pulmonary arterial hypertension,
      especially primary one, and its classification, diagnosis, and possibilities for
      medication. The major role in pathogenesis is ascribed for in situ thrombosis,
      intimal and adventitial proliferation and smooth muscle hypertrophy. Prostacyclin
      analogues, nitric oxide, calcium channel blockers and endothelin-1 receptor
      blockers are the most important medicines, which decrease pressure in the
      pulmonary artery. The clinical case of the 63-year-old woman, who was ill with
      severe primary pulmonary arterial hypertension, is described in the article.

PMID- 15516829
TI  - Small molecule inhibitors of methionine aminopeptidase type 2 (MetAP-2).
AB  - The protein processing enzyme, methionine aminopeptidase-2 (MetAP-2), has been
      identified as a molecular target of fumagillin and its derivative, TNP-470,
      compounds known to inhibit endothelial cell proliferation and angiogenesis. A
      high-throughput screening program was undertaken to identify selective,
      reversible inhibitors of MetAP-2 in an attempt to discover structurally novel
      anti-angiogenic agents for potential therapeutic use in oncology. Approximately
      90 small-molecule, reversible, selective inhibitors of rhMetAP-2 were identified.
      The most potent of these compounds contained a singly-substituted triazole moiety
      which exhibited an IC50 of 8 nM (95% confidence limits 5 to 13 nM) and was highly
      selective for MetAP-2 over MetAP-1 (approximately 60-fold difference in IC50
      values). Unlike fumagillin, these MetAP-2 inhibitors failed to significantly
      inhibit growth factor-stimulated endothelial cell (HUVEC) proliferation or to
      suppress angiogenesis in the in vitro aortic ring explant model of microvessel
      outgrowth. The MetAP-2-inhibitory activity of these compounds was dependent on
      the divalent cation used as the metalloenzyme activating cofactor for MetAP-2.
      These inhibitors were identified using cobalt(II)-activated recombinant human
      MetAP-2 for screening compound libraries. When manganese (Mn2+) was substituted
      for cobalt following EDTA treatment and extensive dialysis of the MetAP-2
      protein, these inhibitors were significantly less potent (40-fold increase in
      IC50) as inhibitors of MetAP-2. These results support the recent hypothesis that
      cobalt may not be the relevant divalent metal ion cofactor for MetAP-2 in cells
      and may explain the observed absence of cell-based activity using potent triazole
      inhibitors of cobalt-activated MetAP-2.

PMID- 15516830
TI  - Hanging-drop multicellular spheroids as a model of tumour angiogenesis.
AB  - The establishment of a vascular network within tumours is a key step in the
      progression towards an aggressive, metastatic state, with poor prognosis. We have
      developed a novel in vitro model to specifically capture the interaction between
      endothelial cells and solid tumours. Micro-vascularised in vitro tumour
      constructs were produced by introducing endothelial cells to multicellular
      spheroids formed in hanging drops. Upon introduction, the endothelial cells
      migrated into the tumour spheroid, establishing tubular networks and luminal
      structures. This system relies on the natural pro-angiogenic capacity of
      multicellular spheroids, and does not require the addition of exogenous
      angiogenic factors, or use of extracellular-matrix substitutes.

PMID- 15516831
TI  - Inhibition of FGF receptor activity in glioma implanted into the mouse brain
      using the tetracyclin-regulated expression system.
AB  - We have investigated growth and vascularization of malignant glioma in mice upon
      conditional inhibition of fibroblast growth factor (FGF) receptor activity. C6
      rat glioma cells were transfected with a dominant-negative fibroblast growth
      factor receptor-2 (FGFR2-DN) cDNA under the control of a tetracycline-regulated
      expression promoter (tet off) and implanted in the brain of immunodeficient mice.
      Magnetic resonance imaging analysis showed a significant decrease in tumor growth
      14 days after implantation when FGFR2-DN was expressed compared to control. This
      size difference disappeared after 20 days. However, after 20 days, tumor and
      endothelial cells apoptosis were higher in the FGFR2-DN group and consequently
      angiogenesis was decreased whereas tumor cells were similarly associated with
      blood vessels at the tumor periphery. Pericyte coverage was not different between
      the two groups but a higher amount of pericytes not associated with vessels was
      found in the FGFR2-DN expressing group. This demonstrates, that conditional
      expression of inhibitor of FGF receptor activity in gliomas implanted in the
      brain of immunodeficient mice can be achieved efficiently, and that FGFs are
      major players in glioma development and in glioma angiogenesis.

PMID- 15516832
TI  - Withaferin A is a potent inhibitor of angiogenesis.
AB  - The medicinal plant Withania somnifera is widely researched for its anti
      inflammatory, cardioactive and central nervous system effects. In Ayurveda , the
      major Traditional Indian medicine system, extracts from W. somnifera are
      distinctively employed for the treatment of arthritis and menstrual disorders.
      Because these conditions involve angiogenic processes we hypothesized that the W.
      somnifera extracts might contain angiogenesis inhibitors. We employed an
      endothelial cell-sprouting assay to monitor the purification of substances from
      W. somnifera root extracts and isolated as the active principle the previously
      known natural product withaferin A. We show that withaferin A inhibits human
      umbilical vein endothelial cell (HUVEC) sprouting in three-dimensional collagen-I
      matrix at doses which are relevant to NF-kappa B-inhibitory activity. Withaferin
      A inhibits cell proliferation in HUVECs (IC50 =12 nM) at doses that are
      significantly lower than those required for tumor cell lines through a process
      associated with inhibition of cyclin D1 expression. We propose that the
      inhibition of NF-kappa B by withaferin A in HUVECs occurs by interference with
      the ubiquitin-mediated proteasome pathway as suggested by the increased levels of
      poly-ubiquitinated proteins. Finally, withaferin A is shown to exert potent anti
      angiogenic activity in vivo at doses that are 500-fold lower than those
      previously reported to exert anti-tumor activity in vivo. In conclusion, our
      findings identify a novel mode of action of withaferin A, which highlights the
      potential use of this natural product for cancer treatment or prevention.

PMID- 15516833
TI  - Tumor-derived prostaglandin E2 and transforming growth factor-beta stimulate
      endothelial cell motility through inhibition of protein phosphatase-2A and
      involvement of PTEN and phosphatidylinositide 3-kinase.
AB  - Tumor vascularization is a complex process that requires structural
      reorganization and increased motility by endothelial cells. Studies were
      conducted to identify the tumor-derived mediators and signaling pathways that
      lead to this increased endothelial cell motility. Using the Lewis lung carcinoma
      (LLC) tumor model, these studies showed that prostaglandin E2 (PGE2) and
      transforming growth factor-beta (TGFbeta) were the mediators that were
      responsible for the migration-stimulatory activity produced by the tumor cells.
      The response of endothelial cells to these tumor-derived motility-stimulatory
      factors involved a decline in the activity of the serine/threonine phosphatase PP
      2A. Inhibition PP-2A either pharmacologically or genetically increased
      endothelial cell migration. Concurrent with the decline in PP-2A activity as a
      result of exposure to PGE2/TGFbeta was a loss of PP-2A co-precipitation with the
      inositol phosphatase PTEN and an increase in the PTEN serine phosphorylation
      level. Since hyperphosphorylation has been shown to inhibit the ability of PTEN
      to act as an antagonist to phosphatidylinositide 3-kinase (PI3K), the role of
      PI3K in PGE2/TGFbeta-stimulated migration was examined. These studies showed that
      the increased endothelial cell motility that resulted from PGE2/TGFbeta
      inhibition of PP-2A was dependent on PI3K.

PMID- 15516834
TI  - Protamine enhances uptake of cationic liposomes in angiogenic microvessels.
AB  - INTRODUCTION: Cationic liposomes have been shown to target angiogenic endothelial
      cells of solid tumours. Supposing a charge-related mechanism might be responsible
      for liposome-endothelial interaction, we investigated the effect of intravenous
      pre-injection of the charged molecules protamine, a polycationic protein, and
      fucoidan, a polyanionic polysaccharide on the accumulation of cationic liposomes
      within the blood vessels of a solid tumour. MATERIALS AND METHODS: Experiments
      were performed using the amelanotic hamster melanoma A-Mel-3 growing in a dorsal
      skinfold chamber of hamsters. Accumulation of fluorescently-labelled cationic
      liposomes was quantified by intravital macroscopy and digital image analysis of
      tumour (t) and surrounding normal host tissue (n) over an observation period of 6
      h. All animals received an i.v. injection of cationic liposomes. Animals of the
      control group were pre-treated with an i.v. injection of 0.9% saline, while
      animals of group 2 received positively charged protamine and animals of group 3
      negatively charged fucoidan prior to liposome injection. RESULTS: In control
      animals i.v. injection of cationic liposomes revealed a preferential targeting of
      the tumour vessels, indicated by a maximal t/n ratio of 2.2 +/- 0.24 and a
      maximal fluorescence intensity (fmax) corresponding to the tumour of 66 +/- 12 [%
      standard]. While there were no significant differences of liposome accumulation
      within normal host tissue, accumulation of cationic liposomes within the tumour
      was significantly enhanced after the pre-administration of protamine (fmax: 117
      +/- 12 [% standard]). The t/n ratio was significantly increased in protamine pre
      treated animals (5.3 +/- 1.7) in comparison to control and fucoidan treated
      animals. In contrast, pre-injection of fucoidan resulted in reduced maximal
      fluorescence intensities in tumour (47 +/- 8 [% standard]) and normal surrounding
      host tissue. CONCLUSION: Pre-administration of protamine increases the
      accumulation of cationic liposomes in a solid tumour animal model causing an
      increased selectivity of cationic liposomes in targeting angiogenic microvessels.

PMID- 15516835
TI  - Bioinformatic analysis of primary endothelial cell gene array data illustrated by
      the analysis of transcriptome changes in endothelial cells exposed to VEGF-A and
      PlGF.
AB  - We recently published a review in this journal describing the design,
      hybridisation and basic data processing required to use gene arrays to
      investigate vascular biology (Evans et al. Angiogenesis 2003; 6: 93-104). Here,
      we build on this review by describing a set of powerful and robust methods for
      the analysis and interpretation of gene array data derived from primary vascular
      cell cultures. First, we describe the evaluation of transcriptome heterogeneity
      between primary cultures derived from different individuals, and estimation of
      the false discovery rate introduced by this heterogeneity and by experimental
      noise. Then, we discuss the appropriate use of Bayesian t-tests, clustering and
      independent component analysis to mine the data. We illustrate these principles
      by analysis of a previously unpublished set of gene array data in which human
      umbilical vein endothelial cells (HUVEC) cultured in either rich or low-serum
      media were exposed to vascular endothelial growth factor (VEGF)-A165 or placental
      growth factor (PlGF)-1(131). We have used Affymetrix U95A gene arrays to map the
      effects of these factors on the HUVEC transcriptome. These experiments followed a
      paired design and were biologically replicated three times. In addition, one
      experiment was repeated using serial analysis of gene expression (SAGE). In
      contrast to some previous studies, we found that VEGF-A and PlGF consistently
      regulated only small, non-overlapping and culture media-dependant sets of HUVEC
      transcripts, despite causing significant cell biological changes.

PMID- 15516837
TI  - Abstracts of the 15th Endothelial Cell Research Symposium. Maastricht, the
      Netherlands, 23 November 2004.

PMID- 15516836
TI  - In vivo videomicroscopy reveals differential effects of the vascular-targeting
      agent ZD6126 and the anti-angiogenic agent ZD6474 on vascular function in a liver
      metastasis model.
AB  - Metastases require a functional blood supply for progressive growth. Thus,
      therapies that target metastatic vasculature have potential clinical utility. The
      effects of the vascular-targeting agent (VTA), ZD6126, and the anti-angiogenic
      agent, ZD6474, on vascular development and function within metastases were
      compared in an experimental liver metastasis model. Ras-transformed PAP2
      fibroblasts were injected into the mesenteric veins of SCID mice to produce a
      control liver metastasis burden of approximately 40% at 14 days. Mice given a
      single dose of ZD6126 (200 mg/kg, i.p.) on day 13 were examined 24 h later.
      Histology revealed a significant reduction in metastatic burden, associated with
      extensive tumor necrosis, increased tumor cell apoptosis and a reduction in tumor
      associated vasculature. In vivo videomicroscopy (IVVM) revealed disrupted, non
      functional vascular channels within metastases, with no blood flow. Mice given
      ZD6474 on days 4 to 10 (50 mg/kg daily, oral gavage) were examined on day 11.
      Histology revealed a lower metastatic burden, significant reductions in
      metastasis size and vasculature, and a significant increase in tumor cell
      apoptosis. IVVM revealed extensive reductions in vascularity and blood flow
      within metastases. Neither ZD6126 nor ZD6474 treatment affected surrounding
      normal liver tissue. This study shows that both agents can reduce experimental
      liver metastasis with no apparent effect on normal vasculature. However, these
      reductions were attained through distinct effects on the metastatic vasculature.
      Understanding differences in the modes of action of VTAs and anti-angiogenic
      agents will be important in optimizing their clinical application and in
      developing appropriate combination strategies.

PMID- 15516841
TI  - The Jewish people: their ethnic history, genetic disorders and specific cancer
      susceptibility.
AB  - The Jews are an ancient and unique group of people linked by language, religion
      and customs in spite of their major geographical shifts, expulsions, forced
      conversions and massacres throughout their entire history. As a result of these
      historical events that led to repeated migration, the Jewish people became
      dispersed into various ethnic sub-groups. Between these ethnic groups exists
      heterogeneity, as well as some similarities, to the populations amongst whom they
      lived. Rare genetic diseases have been reported to be prevalent among the
      different groups of Jews, which for the most part can be explained by random
      genetic drift together with intra-familial marriages. In this publication, we
      will briefly discuss the origin of the various ethnic groups and some of the
      genetic diseases commonly found in them, with emphasis on the Ashkenazim, their
      prevalent genetic diseases and cancer susceptibility.

PMID- 15516840
TI  - Cancer in Jews: introduction and overview.
AB  - This article is based upon a literature overview of cancer in Jews. It involves a
      comparison of variation in incidence and prevalence rates between Jews and non
      Jews. However, the reader must exercise a certain amount of skepticism when
      considering secular changes in cancer incidence and prevalence and the public
      health implications of such cancer variation. Ashkenazi Jews have a lifetime CRC
      risk of 9--15%. This elevated CRC risk is similar to that of individuals in the
      "familial risk'' category, and differs strikingly from the 5-6% CRC risk for non
      Ashkenazi members of general Western populations. A MedLine search tested the
      hypothesis that site-specific and/or all-cancer incidence and mortality rates are
      either higher or lower than expected in Ashkenazi Jews worldwide, when compared
      with reference populations. Results showed that all cancer incidence and
      mortality is not higher in Ashkenazi Jews when compared to North American non
      Hispanic whites. Indeed, rates for some cancers, such as carcinoma of the lung in
      Ashkenazi males, are low; this example is likely attributable in large part to
      decreased tobacco use. Carcinoma of the ovary, pancreas, stomach, and non
      Hodgkin's lymphoma have a higher incidence rate in Ashkenazi. Even though BRCA1
      and BRCA2 founder mutations which predispose to carcinoma of the breast and ovary
      appear increased in Ashkenazi breast cancer affected women, there was no evidence
      supporting an elevated risk of breast cancer among Ashkenazi women. Our primary
      concern, however, is that Ashkenazi Jews may have one of the highest lifetime CRC
      risks of any ethnic group in the world, a risk that diverges significantly from
      that of the general population; therein, it logically calls for more intensive
      CRC screening guidelines. We have emphasized that the reader use caution in the
      interpretation of statistics which portray variation in incidence and prevalence
      figures for cancer in any racial, ethnic, or religious group, inclusive, of
      course, of Jews. Clearly, more research will be required in the interest of
      accuracy in the understanding of these cancer variations, since they portend the
      need for special cancer control strategies. A lesser degree of attention can then
      be given to carcinoma of the penis and uterine cervix, which occur very
      infrequently in Jews. We urge our colleagues to continue to probe further into
      these statistical differences in cancer's incidence and prevalence in order to
      garner a better understanding of cancer's etiology and pathogenesis.

PMID- 15516842
TI  - Ashkenazi Jewish genetic disorders.
AB  - The frequency of several genes responsible for 'single-gene' disorders and
      disease predispositions is higher among Ashkenazi Jews than among Sephardi Jews
      and non-Jews. The disparity is most likely the result of founder effect and
      genetic drift, rather than heterozygote advantage. The more common Mendelian
      Ashkenazi Jewish genetic disorders are summarized, and examples of variable
      expressivity and penetrance, inconsistent genotype-phenotype correlation, and
      potential modifiers are presented. The importance of genetic counseling in both
      the pre- and post-test phases of population screening is emphasized.

PMID- 15516843
TI  - Trends in colorectal cancer incidence and mortality in the Israeli Jewish ethnic
      populations.
AB  - BACKGROUND: Ashkenazi Jews, as compared to non-European Jews and non-Jews, are at
      increased risk for colorectal cancer (CRC), this is attributed to genetic
      susceptibility and/or lifestyle. AIMS: To follow Israeli long-term trends in CRC
      incidence and mortality and their associations with ethnicity. METHODS: All
      Israeli CRC data accumulated 1970-2001 was used, age standardized rates (adjusted
      to world standard population) was computed by cancer site, US Surveillance,
      Epidemiology and End Results Program (SEER) Stage and ethnic group (continent of
      birth: Europe-America, Asia, Africa, Israel). RESULTS: From 1970, CRC incidence
      increased 190% in males and 140% in females; mainly colon cancer (270% and 185%
      respectively) (P < 0.01), while rectal cancer incidence decreased and is now
      stable. Stage 3 CRC increased while stage 4 decreased significantly (P < 0.01 for
      both). In 2001, CRC incidence per 100,000 in European-American-born males was
      48.3, Asian and African born 35.5 and Israeli born 32.7 (relative risk (RR) 1.36,
      P = 0.03), while European-American female rates were 35 and all the others 26 (RR
      1.35, P < 0.01). Overall survival increased 9% over 30 years (P < 0.01), 5 years
      survival since 1988-1996 for European-American born was 43.1%, Asian 46.7%,
      African 47.5% and Israeli 55.8%. Stage-2 CRC 5 years survivals for 1970-1996
      (most had no post surgical treatment) for European-American born were 41.7%,
      Asian and African 44.8% and Israeli 53.4% (P < 0.05). Stage-3 CRC survivals (most
      received adjuvant therapy in addition to surgery) for European-American born was
      38.8%, Asian and African 43.3% and Israeli 45.1% (P < 0.01). CONCLUSIONS: Colon
      cancer has increased in Israel, mainly in males and European-American born.
      Israeli-born Jews (of 20 to 60% mixed ethnicity and lifestyle habits) have the
      lowest incidence and best survival data for stages-2 and -3 CRC. There is
      evidence of ethnic survival advantage and possibly in response to adjuvant
      oncological therapy.

PMID- 15516844
TI  - Genetic factors and colorectal cancer in Ashkenazi Jews.
AB  - The observed increased incidence of colorectal cancer in Ashkenazi Jews compared
      to other populations is unexplained but likely has a genetic component. The
      I1307K APC polymorphism/mutation is carried by 6-8% of Ashkenazim and increases
      the risk of colorectal cancer 1.5-2 fold. There are few differences between the
      phenotype of colorectal cancer in I1307K carriers and sporadic cases. It is
      estimated that the mutation accounts for 6% of cases of colorectal cancer in Jews
      of Eastern European heritage. It should not be the subject of mass screening in
      Ashkenazi Jews, although it may be important in cases of familial colorectal
      cancer. Even rarer is the 1906G-->C MSH2 mutation carried by less than 1% of
      Ashkenazim, but as with other HNPCC mutations likely associated with a high risk
      of malignancy. Mutations at 15q13-14 are associated with the colorectal adenoma
      and carcinoma syndrome (CRAC) described in Ashkenazi families. The prevalence of
      the mutation is not known, nor its significance as a cause of colorectal cancer.
      Despite the paucity of genetic explanations for the high risk of colorectal
      cancer in Ashkenazim, that risk warrants aggressive colorectal cancer screening
      and particular attention to family history of malignancy in all Jews of Ashkenazi
      descent.

PMID- 15516845
TI  - A636P testing in Ashkenazi Jews.
AB  - Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominantly
      inherited colorectal cancer syndrome attributable to mutations in one of several
      DNA mismatch repair genes, most commonly MLH1 and MSH2 . In certain populations,
      founder mutations account for a substantial portion of HNPCC. In this report we
      summarize the literature and our personal experience testing for a specific
      founder mutation in the Ashkenazi Jewish population, MSH2*1906G > C , also known
      as A636P. Although rare in the general population, the A636P mutation is detected
      in up to 7% of Ashkenazi Jewish patients with early age-of-onset colorectal
      cancer, and may account for up to one third of HNPCC in the Ashkenazi Jewish
      population. In addition, we summarize our initial experience with a prospective
      A636P testing protocol aimed at Ashkenazi Jewish patients at high or intermediate
      risk for harboring the A636P mutation.

PMID- 15516846
TI  - Inflammatory bowel disease in Ashkenazi Jews: implications for familial
      colorectal cancer.
AB  - Inflammatory bowel disease (IBD) has a multifactorial etiology and includes
      ulcerative colitis (UC) and Crohn's disease (CD). Powerful epidemiologic and
      genetic studies have provided ample evidence that a subset of both CD and UC are
      attributable to a likely primary genetic etiology. This is evidenced by the
      recent identification of the IBD1 gene ( NOD2 ) mutations which show an
      association with susceptibility to CD. The IBD complex shows a significant
      increased frequency in Jews when compared to non-Jews. While there is an
      increased incidence of colorectal cancer (CRC) in patients with IBD, it
      nevertheless is important to realize that IBD likely accounts for no more than 1
      3% of all cases of CRC in Ashkenazi Jews. Importantly, however, awareness of the
      increased CRC risk in IBD may aid immeasurably in preventive interventions. The
      molecular pathway leading to CRC in IBD appears to differ from the well-known
      adenoma-to-CRC sequence, given the fact that these cancers appear to arise from
      either flat, dysplastic tissue or dysplasia-associated lesions or masses (DALMs).
      An important model, but by no means an absolute one, for colon carcinogenesis in
      IBD follows progression from an absence of dysplasia, to indefinite dysplasia, to
      low-grade dysplasia, on to high-grade dysplasia, and ultimately to invasive CRC.
      This carcinogenic process relates to the disease duration with respect to the
      extent of colonic involvement and may also involve primary sclerosing
      cholangitis. Given this knowledge of an increased risk for CRC in UC and CD,
      surveillance colonoscopy should initially be performed 8-10 years after onset of
      symptoms as opposed to diagnosis, and it should be performed 1-2 years after 8
      years of disease in patients with pancolitis or after 15 years in those with left
      sided colitis. A search for dysplasia of colonic mucosa with biopsies performed
      in all four quadrants every 10 cm throughout the colon is exceedingly important.
      Additional biopsies should be taken of any flat lesions, masses, or strictures.
      Prophylactic colectomy may then be indicated when severe dysplasia is confirmed
      by knowledgeable pathologists.

PMID- 15516848
TI  - Fanconi anemia in Ashkenazi Jews.
AB  - Fanconi anemia (FA) should be included among the genetic diseases that occur at
      high frequency in the Ashkenazi Jewish population. FA exhibits extensive genetic
      heterogeneity; there are currently 11 complementation groups reported, and 8
      (i.e., FANCA, FANCC, FANCD1/BRCA2, FANCD2, FANCE, FANCF, FANCG, and FANCL) genes
      have been isolated. While patients may be from widely diverse ethnic groups, a
      single mutation in complementation group FA-C, c.711 + 4A > T (commonly known as
      IVS4 + 4A > T prior to current nomenclature rules) is unique to FA patients of
      Ashkenazi Jewish ancestry, and has a carrier frequency of greater than 1/100 in
      this population. In addition, a mutation (c.65G > A) in FANCA (FA-A is the most
      common complementation group in non-Jewish patients) and the mutation c.6174delT
      in FANCD1/BRCA2 are also unique to the Ashkenazi Jewish population. Therefore,
      the study of Fanconi anemia can lend insight into the types of cancer
      predisposing genetic diseases specific to the Ashkenazi.

PMID- 15516847
TI  - Familial pancreatic carcinoma in Jews.
AB  - Pancreatic cancer (PC) is the most fatal of all gastrointestinal cancers, wherein
      its mortality compares strikingly with its incidence. Unfortunately, 80-90% of
      PCs are diagnosed in the nonresectable stage. While the lifetime risk of PC in
      developed countries is approximately 1-3%, it is the fifth most common cause of
      cancer deaths among both males and females in Western countries. It occurs in
      excess in Jews. Approximately 5-10% of PC shows familial clustering. Examination
      of such familial clusters must take into consideration cancers of diverse
      anatomic sites, such as malignant melanoma in the familial atypical multiple
      melanoma (FAMMM) syndrome due to the CDKN2A (p16) germline mutation, and
      combinations of colorectal and endometrial carcinoma, ovarian carcinoma, and
      several other cancers in hereditary nonpolyposis colorectal cancer (HNPCC), which
      are due to mismatch repair germline mutations, the most common of which are MSH2
      and MLH1 . Other hereditary disorders predisposing to PC include Peutz-Jeghers
      syndrome, due to the STK11 mutation, familial pancreatitis due to the cationic
      trypsinogen gene, site-specific familial pancreatic cancer which may be due to
      the 4q32-34 mutation, hereditary breast-ovarian cancer (HBOC) syndrome that is
      due to BRCA2 and possibly some families with HBOC that is due to BRCA1 , familial
      adenomatous polyposis due to the ATP gene, and ataxia telangiectasia due to the
      ATM germline mutation. This extant heterogeneity mandates that the physician be
      knowledgeable about these PC-prone syndromes which play such an important role
      when considering the differential diagnosis of hereditary PC. Unfortunately,
      there are no PC screening programs with acceptable sensitivity and specificity.
      However, the gold standard for screening at this time is endoscopic ultrasound.
      Clearly, there is a great need for the development of novel screening approaches
      with acceptable sensitivity and specificity. Further research is needed to
      elucidate those etiologic factors that contribute to the apparent excess of PC in
      Ashkenazi Jews. Attention should also be given to the search for mutations
      predisposing to PC in Jews so that opportunities to learn more about the
      disease's pathogenesis, as well as screening and control, may take place.

PMID- 15516849
TI  - Hereditary breast cancer in Jews.
AB  - A family history of breast cancer poses higher risks for Jewish versus non-Jewish
      women, particularly for early-onset breast cancer. This appears to be due in
      large part to the high prevalence (2.5%) of three BRCA1 and BRCA2 founder
      mutations in Ashkenazi Jews. About 4 to 8% of non-Jewish male breast cancer cases
      versus 19% of Jewish male breast cancer cases carry germline BRCA mutations.
      Jewish women are disproportionately impacted by BRCA mutations throughout life,
      with a 10% carrier rate for breast cancer diagnosed at any age and a 21 to 30%
      carrier rate for breast cancer diagnosed by age 40. Comparable rates in non
      Jewish populations are 6.1% for breast cancer diagnosed before age 50. Lifetime
      penetrance estimates based on genotyping of probands have ranged widely in Jewish
      and non-Jewish populations. However, a study of 1008 Jewish women with breast
      cancer which extended genotyping to relatives found high penetrance rates with
      considerably smaller standard errors. This study and studies of early-onset
      incident breast cancer in non-Jews have found that at least half of high-risk
      cases would be missed by family history screening alone. While the carrier rate
      in non-Jewish populations is too low to consider genetic screening, the carrier
      rate in Ashkenazi Jews is high and genetic screening poses fewer technical
      barriers. The high genetic attributable cancer risks of Ashkenazi BRCA founder
      mutations, the sobering lethality of ovarian and early onset breast cancers, and
      the increasing clarity about effectiveness of medical interventions make
      imperative further dialogue and research to keep guidelines for genetic screening
      up to date.

PMID- 15516850
TI  - Hereditary ovarian cancer in Ashkenazi Jews.
AB  - Ovarian cancer is the fourth leading cause of cancer deaths among American women.
      While women in both the Ashkenazi and non-Ashkenazi populations have an estimated
      1.7% lifetime risk of acquiring malignancy, the proportion of hereditary ovarian
      cancer is much higher in the Ashkenazim. Most of this increased proportion of
      hereditary ovarian cancer risk is accounted for by inherited mutations in the
      BRCA1 and BRCA2 genes. In the Ashkenazi Jewish population, 29 to 41% of ovarian
      cancer is believed to be secondary to inheriting one of three founder mutations
      in BRCA 1 and BRCA 2, while only 10% of ovarian cancer is attributed to mutations
      of these genes in non-Ashkenazim. In the US population in general, it is
      estimated that between 1 out of 345 and 1 out of 1000 individuals carries a BRCA
      mutation, compared with approximately 1 in 40 individuals of Ashkenazi Jewish
      descent. The ovarian cancer risk up to age 70 associated with BRCA mutation
      carriers has been reported to be as high as 66% for BRCA1 and 27% for BRCA2
      mutation carriers. Ovarian cancer in Ashkenazi kindreds has served as a model for
      the study of the histopathology of inherited ovarian cancers as well as for the
      study of risk reduction and screening among all women at inherited risk of
      ovarian cancer.

PMID- 15516855
TI  - Editorial.

PMID- 15516856
TI  - Biologic rationale for the use of beta-blockers in the treatment of heart
      failure.
AB  - Enhanced and sustained cardiac adrenergic drive occurs in heart failure and
      contributes, in part, to the progression of left ventricular (LV) dysfunction and
      remodeling that are characteristic features of this disease state. Enhanced
      sympathetic drive in heart failure can lead to down-regulation and
      desensitization of cardiac beta-adrenergic receptors with a consequent impairment
      of myocardial reserve and exercise tolerance. This sympathoadrenergic
      maladaptation can also lead to cellular abnormalities in the failing heart
      manifested by defects in calcium cycling within the sarcoplasmic reticulum, by
      defects in myocardial energetics and by ongoing loss of cardiomyocytes through
      necrosis or apoptosis. Sympathoadrenergic overdrive in heart failure can also
      trigger the induction of the fetal gene program, a maladaptation that can lead to
      further compromise of the contractile state. Chronic treatment with beta-blockers
      in patients with heart failure and in animals with experimentally-induced heart
      failure has been shown to reverse, prevent, or at the very least, arrest many, if
      not all, of these adverse processes. Beta-blockers improve function of the
      failing LV, prevent or reverse progressive LV dilation, chamber sphericity and
      hypertrophy, and consequently positively impact cardiac remodeling. Beta-blockers
      also reduce heart rate and LV wall stress leading to reduced myocardial oxygen
      consumption, a clear benefit to the failing heart. Beta-blockers can also improve
      the intrinsic contractile function of cardiomyocytes and have also been shown to
      improve myocardial energetics in heart failure possibly through a desirable shift
      in substrate utilization. Recent studies from our laboratories have also shown
      that chronic therapy with beta-blockers in heart failure can attenuate
      cardiomyocyte apoptosis. Finally, chronic therapy with beta-blockers has been
      shown to abrogate induction of the fetal gene program. These benefits provide
      strong reinforcement to the clinical findings that beta-blockers are highly
      beneficial in the management of patients with chronic heart failure and, when
      properly used, afford unequivocal reductions in mortality and morbidity in this
      patient population.

PMID- 15516851
TI  - Peritoneal carcinoma in women with genetic susceptibility: implications for
      Jewish populations.
AB  - Women from families with multiple cases of breast and ovarian cancer,
      specifically those who carry cancer-associated mutations of BRCA1 or BRCA2 are at
      increased life-time risk for peritoneal carcinoma, even after previous surgery to
      remove the ovaries, fallopian tubes and uterus. Hereditary breast-ovarian cancer
      (HBOC) syndrome and the associated BRCA1 and BRCA2 mutations are particularly
      prevalent in women of Jewish lineage, and specific BRCA1 and BRCA2 germline
      mutations have been linked with peritoneal carcinoma and HBOC syndrome in Jewish
      populations, especially those of Ashkenazi descent. This review presents the
      currently available data and looks forward toward further and better
      understanding of peritoneal carcinoma in women with inherited susceptibility.
      Over 90% of peritoneal cancer in patients from HBOC syndrome kindreds and
      associated with BRCA1 and BRCA2 mutations are serous carcinomas, which is
      equivalent with the proportion of ovarian cancers that are serous carcinomas in
      similar patients. The best indications are that while many peritoneal carcinomas
      in genetically susceptible women may arise directly from malignant transformation
      of the peritoneum, others might represent metastases from primary ovarian or
      fallopian tube carcinomas. Although the incidence of borderline ovarian tumors
      may not be increased in HBOC syndrome kindreds and those who carry cancer
      associated BRCA1 and BRCA2 mutations, these individuals could be susceptible to
      malignant transformation of borderline lesions of the ovaries and peritoneum.
      Moreover, recent reports raise the question of possibly increased risk in Jewish
      carriers of germline BRCA1 mutations for uterine papillary serous carcinoma,
      which could be the source of metastasis to the peritoneum in some cases. The
      penetrance of cancer-associated BRCA1 mutations for ovarian cancer is estimated
      to be 11%-54%, and for BRCA2 mutations the penetrance for ovarian cancer is 11%
      23%. So far, available screening methods appear to be insufficient for early
      detection of many ovarian cancers. Prophylactic oophorectomy has been found to
      reduce the risk for ovarian cancer in women from HBOC kindreds and those who
      carry cancer-associated BRCA1 and BRCA2 mutations, leaving a residual risk for
      peritoneal carcinomatosis of well less than 5%. Therefore, surgical removal of
      the ovaries, fallopian tubes and uterus, after child-bearing has been completed
      and by early in the fifth decade of life, are appropriate prophylactic procedures
      in women whose genetic susceptibility puts them at increased risk for cancers of
      mullerian tract origin, including ovarian and fallopian tube carcinomas and
      possibly serous carcinoma of the uterus. Hysterectomy, as well as salpingo
      oophorectomy, removes the gynecologic organs targeted for malignant
      transformation in genetically susceptible women and simplifies decisions
      regarding hormone replacement therapy and chemical prophylaxis and treatment of
      breast cancer. Unless a transabdominal operative approach is otherwise indicated,
      laparoscopic-assisted transvaginal techniques are well suited for intra-abdominal
      exploration, cytology, biopsies and prophylactic salpingo-oophorectomy and
      hysterectomy in women with hereditary susceptibility to gynecologic cancer.

PMID- 15516857
TI  - B-type natriuretic Peptide and the right heart.
AB  - B-type natriuretic Peptide (BNP) is elevated in conditions with ventricular
      volume and pressure overload. The physiological, diagnostic and therapeutic role
      of BNP in right ventricular (RV) dysfunction and pulmonary arterial hypertension
      (PAH) are reviewed in this article. BNP levels can be used to differentiate
      between breathless patients with a respiratory disease and those with PAH. BNP
      has been shown to correlate with mean pulmonary arterial pressure and pulmonary
      vascular resistance in patients with PAH, whether primary or secondary. BNP is
      also a predictor of mortality in patients with primary pulmonary hypertension.
      These are important clinical implications in that a non-invasive blood test may
      be used to identify patients who require more invasive procedures (such as
      cardiac catheterization). There is increasing evidence that BNP or NT-proBNP
      measurements may also be used to guide therapy (e.g. pulmonary vasorelaxants) in
      PAH. Enhancement of the natriuretic peptide pathway has been shown to reduce
      cardiac hypertrophy and PAH and hence, there may be therapeutic potential via
      recombinant BNP or neutral endopeptidase inhibitors in RV dysfunction and PAH.

PMID- 15516858
TI  - Beta blocker therapy after acute myocardial infarction in patients with heart
      failure and systolic dysfunction.
AB  - The benefit of beta blockade has been well established in acute myocardial
      infarction for several decades, and its benefit in chronic heart failure has been
      proven since the early 1990's. Several large retrospective analyses suggested the
      benefit of beta blockers in post-MI systolic dysfunction. Only recently has the
      benefit of beta blockers been proven in addition to ACE inhibitors, antiplatelet
      agents, and reperfusion therapy. In the year 2000, CAPRICORN became the first
      randomized trial to directly address beta blockade in patients with post
      infarction systolic dysfunction. The trial showed a 23% reduction in all-cause
      mortality with carvedilol, in patients already receiving ACE inhibitors,
      antiplatelet agents, and reperfusion therapy. This is a review of the literature
      on the administration of beta blockade in patients after acute myocardial
      infarction with left ventricular systolic dysfunction, as well as a comment on
      other current treatment modalities for this subset of patients.

PMID- 15516859
TI  - The effects of beta blockers on morbidity and mortality in heart failure.
AB  - Beta-adrenergic receptor blockers are effective in reducing morbidity and
      mortality in heart failure. These drugs slow the progression of heart failure by
      modifying the remodeling process, prevent or delay need for hospital admission
      for heart failure. They reduce both pump failure and sudden arrhythmic death.
      There are many patients that do not receive beta blocker therapy in the heart
      failure population. Patients are often treated with beta blockers not tested in
      clinical trials to demonstrate efficacy in this patient population. Results from
      the recently published trials are summarized to emphasize the proper selection
      and dosage of beta blocker therapy to optimize the care of this high risk
      population.

PMID- 15516860
TI  - Beta-blockers in heart failure: are pharmacological differences clinically
      important?
AB  - Beta-blockers are not an homogeneous group of agents. Only three beta-blockers,
      carvedilol, bisoprolol and metoprolol succinate, have had favorable effects on
      prognosis in controlled clinical trials in the patients with chronic heart
      failure. However, pharmacological differences exist between them. Metoprolol and
      bisoprolol are selective for beta(1)-adrenergic receptors while carvedilol blocks
      also beta(2)-, and alpha(1)- adrenergic receptors, and has associated
      antioxidant, anti-endothelin and antiproliferative properties. In COMET
      carvedilol was associated with a significant reduction in mortality compared to
      metoprolol tartrate further showing that different beta-blockers may have
      different effects on the outcome. These differences may be related to the
      ancillary properties of carvedilol or to its broader antiadrenergic profile.
      However, also more effective and prolonged blockade of beta1 adrenergic receptors
      may occur with carvedilol compared to metoprolol.

PMID- 15516861
TI  - Pharmacokinetics and pharmacodynamics of beta blockers in heart failure.
AB  - Although beta-blockers have been used for nearly three decades in the management
      of heart failure, only recent randomized clinical trials have demonstrated
      substantial benefit in reducing morbidity and mortality. Carvedilol, metoprolol
      succinate and bisprolol have evidence supporting their use in heart failure while
      other beta blockers either lack evidence supporting their use or have not been
      shown to be useful in heart failure. The only currently approved beta-blockers in
      the U.S. for heart failure are metoprolol succinate and carvedilol.Beta-blockers
      differ in their pharmacokinetic and pharmacodynamic properties. It should not be
      assumed that potential benefit in heart failure is a class effect since
      differences in the half-life, volume of distribution, protein binding, and route
      of elimination may give rise to differences in duration of beta blockade and
      potential drug interactions. Furthermore, pharmacodynamic differences exist
      because of selectivity for beta(1), beta(2) or alpha(1) adrenoreceptor blockade
      among the beta-blockers. Receptor kinetics also differ among the beta-blockers
      and this may influence the extent and duration of beta and alpha blockade across
      the category. Carvedilol is an inherently long-acting beta-blocker while the
      duration of beta blockade for metoprolol is dependent on the salt and
      formulation, which is used. Metoprolol tartrate is a short-acting form of
      metoprolol while metoprolol succinate is a longer acting salt and the
      commercially available product is designed as a once daily formulation. A
      recently published trial, the Carvedilol or Metoprolol European Trial (COMET)
      tested carvedilol given twice daily versus metoprolol tartrate given twice daily
      in patients with chronic heart failure. Although carvedilol reduced all cause
      mortality when compared with metoprolol tartrate, extrapolation to similar
      findings with metoprolol succinate are not possible since the pharmacokinetic and
      pharmacodynamic effects of these two formulations are different. Furthermore, the
      dosing of metoprolol tartrate in COMET may have been inadequate based on prior
      studies. Additional studies are needed to compare carvedilol directly to
      metoprolol succinate before concluding inequivalency exists for these two beta
      blockers in heart failure.

PMID- 15516862
TI  - Beta blockers as anti-arrhythmic agents.
AB  - Although beta-adrenergic blocking agents are not always considered anti
      arrhythmic drugs, the results of several recent trials have suggested an anti
      arrhythmic mechanism for at least part of their mortality benefit in the
      treatment of chronic congestive heart failure. We review background experimental
      and clinical evidence for the anti-arrhythmic actions of beta-blockers and then
      review the results of published beta-blocker heart failure trials. A majority of
      trials showed improvement in overall survival as well as reduction in sudden
      death and ventricular arrhythmias with beta-blocker treatment. Although different
      effects were seen with different specific agents, these trials overall support a
      clinically significant anti-arrhythmic effect of several beta-blockers.

PMID- 15516863
TI  - Sex-related differences in heart failure and beta-blockers.
AB  - Under-representation of women in heart failure trials has limited our knowledge
      of heart failure in women to extrapolation of findings from men. Significant sex
      related differences in clinical and laboratory characteristics exist in systolic
      heart failure including better survival in women. The value of various
      therapeutic interventions should be based on proven effect in women and not on an
      assumption based on proven benefit in men. Among the medications currently
      recommended for patients with systolic heart failure, beta-blockers have the
      strongest data supporting their efficacy in women.

PMID- 15516864
TI  - Beta blocker therapy in African American patients with heart failure.
AB  - Data from a number of clinical trials of beta blocker therapy in heart failure,
      although limited in the size of African American patients included, suggest that
      they achieve a similar benefit as Caucasians. African Americans were usually at
      higher risk when enrolled in all of these studies with a higher incidence of
      hypertension and diabetes mellitus. The only exception is the Beta Blocker
      Evaluation of Survival Trial (BEST) that studied the efficacy of Bucindolol in
      heart failure. In that study there appeared to be a unique differential effect in
      African Americans compared to Caucasians which may have been in part related to
      the severity of the disease.

PMID- 15516865
TI  - Magnetic and hydrogel composite materials for hyperthermia applications.
AB  - Micron-sized magnetic particles (Fe3O4) were dispersed in a polyvinyl alcohol
      hydrogel to study their potential for hyperthermia applications. Heating
      characteristics of this ferrogel in an alternating magnetic field (375 kHz) were
      investigated. The results indicate that the amount of heat generated depends on
      the Fe3O4 content and magnetic field amplitude. A stable maximum temperature
      ranging from 43 to 47 degrees C was successfully achieved within 5-6 min. The
      maximum temperature was a function of Fe3O4 concentration. A specific absorption
      rate of up to 8.7 W/g Fe3O4 was achieved; this value was found to depend on the
      magnetic field strength. Hysteresis loss is the main contribution to the heating
      effect experienced by the sample.

PMID- 15516866
TI  - Mechanical characterisation of a bone defect model filled with ceramic cements.
AB  - Ceramic bone substitute materials are often used to fill defects in comminuted
      articular fractures. In an in vivo study [1], calcium phosphate cements have been
      injected into highly loaded slot defects in the proximal tibial metaphysis.
      During healing, cracks were formed mostly in the proximal anterior aspect of the
      implanted cement and wedge-like gaps formed between the tibial plateau and the
      cement. Mechanical ex vivo tests were done to investigate the mechanical
      competence of the bone cement in such a defect situation. Entirely filled defects
      were loaded with up to 4.5 kN until they failed. Cyclic loading of the proximal
      tibiae caused micro fragmentation of the cement after 1000 cycles at 1.5-2.0 kN
      load. This aspect was comparable to cement fragmentation observed in vivo. Large
      defects in highly loaded areas should therefore additionally be stabilised with
      metallic implants. The ceramic cement can only be used as a filler material,
      which can be replaced by new bone upon resorption.

PMID- 15516867
TI  - Bonelike apatite formation on niobium metal treated in aqueous NaOH.
AB  - The essential condition for a biomaterial to bond to the living bone is the
      formation of a biologically active bonelike apatite on its surface. In the
      present work, it has been demonstrated that chemical treatment can be used to
      create a calcium phosphate (CaP) surface layer, which might provide the alkali
      treated Nb metal with bone-bonding capability. Soaking Nb samples in 0.5 M NaOH,
      at 25 degrees C for 24 h produced a nano-porous approximately 40 nm thick
      amorphous sodium niobate hydrogel layer on their surface. Immersion in a
      simulated body fluid (SBF) lead to the deposition of an amorphous calcium
      phosphate layer on the alkali treated Nb. The formation of calcium phosphate is
      assumed to be a result of the local pH increase caused by the cathodic reaction
      of oxygen reduction on the finely porous surface of the alkali-treated metal. The
      local rise in pH increased the ionic activity product of hydroxyapatite and lead
      to the precipitation of CaP from SBF that was already supersaturated with respect
      to the apatite. The formation of a similar CaP layer upon implantation of alkali
      treated Nb into the human body should promote the bonding of the implant to the
      surrounding bone. This bone bonding capability could make Nb metal an attractive
      material for hard tissue replacements.

PMID- 15516868
TI  - In vitro blood compatibility of heparin-immobilized polyurethane containing ester
      groups in the side chain.
AB  - In a previous study, we reported on the synthesis of heparin-immobilized
      polyetherurethanes containing ester groups in the side chain. In this study, the
      blood compatibility of heparin-immobilized polyurethanes was investigated using
      in vitro plasma recalcification time (PRT), activated partial thromboplastin time
      (APTT), platelet adhesion and activation and peripheral blood mononuclear cell
      (PBMC) adhesion and activation. In the experiment with plasma proteins, the PRT
      of the polyurethane (PU) surface was prolonged by polyethylene oxide (PEO)
      grafting and further prolonged by heparin immobilization. The APTT was prolonged
      on the PU-C-H and PU-P-H, suggesting the binding of immobilized heparin to the
      antithrombin III. The percentage of platelet adhesion on the PU was almost the
      same as that on carboxylic acid-introduced PU (PU-C), but was slightly decreased
      by PEO grafting and further decreased by heparin immobilization. The release of
      serotonin from the adhering platelets was slightly suppressed on the PEO-grafted
      PU yet significantly suppressed on the heparin-immobilized PUs. In the PBMC
      experiments, the adhesion and activation of the cells were significantly
      suppressed on the heparin-immobilized PUs, and the amount of interleukin-6 (IL-6)
      released from the PBMCs stimulated with the surface-modified PUs decreased with a
      decrease in the PBMC adhesion.

PMID- 15516869
TI  - Preparation and characterization of bioactive and biodegradable
      wollastonite/poly(D,L-lactic acid) composite scaffolds.
AB  - Composite scaffolds of poly(D,L-lactic acid) (PDLLA) with bioactive wollastonite
      were fabricated by the conventional solvent casting-particulate leaching method.
      The pore structures and morphology of the scaffolds were determined by scanning
      electron microscopy (SEM). The bioactivity of the composites was evaluated by
      soaking in a simulated body fluid (SBF), and the formation of the hydroxyapatite
      (HAp) layer was determined by SEM and energy-dispersive spectrometer. The results
      showed that the wollastonite/PDLLA composites were bioactive as it induced the
      formation of HAp on the surface of the composite scaffolds after soaking in SBF
      for seven days. In addition, pH and ion concentration changes of SBF solutions
      with composite scaffolds were examined. The results showed that the composites
      could release Ca and Si ions, which could neutralize the acidic degradation by
      products of the PDLLA, and stabilize the pH of the SBF solutions between 6.7 and
      7.2 within a three-week soaking period. Furthermore, the measurements of the
      water contact angles suggested that incorporation of wollastonite into PDLLA
      could improve the hydrophilicity of the composites and the enhancement was
      dependent on the wollastonite content. All these results suggest that
      incorporation of wollastonite into PDLLA might be a useful approach for the
      preparation of composite scaffolds for tissue repair and tissue-engineering
      applications.

PMID- 15516870
TI  - Probing the origins and control of shrinkage stress in dental resin-composites:
      I. Shrinkage stress characterization technique.
AB  - The accurate and reliable characterization of the polymerization shrinkage stress
      is becoming increasingly important, as the shrinkage stress still is a major
      drawback of current dimethacrylate-based dental materials and restricts its range
      of applications. The purpose of this research is to develop a novel shrinkage
      stress measurement device to elucidate the shrinkage stress evolution of dental
      restorative composites while allowing for controlled sample deformation during
      the polymerization. Furthermore, the device is designed to mimic the clinically
      relevant cusp-to-cusp displacement by systematically adjusting the instrument
      compliance, the bonded surface area/unbonded area by sample geometry, and the
      total bonded area by sample diameter. The stress measurement device based on the
      cantilever beam deflection theory has been successfully developed and
      characterized using a commercial dental composite. It was shown that this device
      is a highly effective, practical and reliable shrinkage stress measurement tool,
      which enables its facile applications to the investigation of shrinkage stress
      kinetics of both commercial and experimental composites, as well as for probing
      various aspects that dictate shrinkage stress development.

PMID- 15516871
TI  - Preparation and characterisation in simulated body conditions of glutaraldehyde
      crosslinked chitosan membranes.
AB  - Chitosan membranes, aimed at biomedical applications, were prepared by a solvent
      casting methodology. Crosslinking was previously performed in acetic acid
      solution with glutaraldehyde, in order to obtain different degrees of
      crosslinking. Some membranes were neutralised in a NaOH solution. Mechanical
      tensile tests comprised quasi-static experiments at constant stress rate and
      temperature sweep dynamic mechanical analysis tests. This included measurements
      with the samples immersed in isotonic saline solution at 37 degrees C, in order
      to simulate physiological conditions, that were performed using a specific liquid
      container. It was observed that for higher crosslinking levels the membranes
      become stiffer but their strength decreases; these results are in agreement with
      swelling tests, also performed at body temperature. All the membranes exhibited
      similar and significant damping properties in wet conditions, which were stable
      in a broad temperature range. Weight loss measurements showed that the developed
      membranes degrade slowly up to 60 days. Cytotoxicity screening, using cell
      culture tests, showed that eventually such materials could be adequate for use in
      biomedical applications.

PMID- 15516872
TI  - Development of tissue scaffolds using selective laser sintering of polyvinyl
      alcohol/hydroxyapatite biocomposite for craniofacial and joint defects.
AB  - The growing interest in scaffold-guided tissue engineering (TE) to guide and
      support cell proliferation in the repair and replacement of craniofacial and
      joint defects gave rise to the quest for a precise technique to create such
      scaffolds. Conventional manual-based fabrication techniques have several
      limitations such as the lack of reproducibility and precision. Rapid prototyping
      (RP) has been identified as a promising technique capable of building complex
      objects with pre-defined macro- and microstructures. The research focussed on the
      viability of using the selective laser sintering (SLS) RP technique for creating
      TE scaffolds. A biocomposite blend comprising of polyvinyl alcohol (PVA) and
      hydroxyapatite (HA) was used in SLS to study the feasibility of the blend to
      develop scaffolds. The biocomposite blends obtained via spray-drying technique
      and physical blending were subjected to laser-sintering to produce test
      specimens. The SLS-fabricated test specimens were characterized using scanning
      electron microscopy and X-ray diffraction. The test specimens were also tested
      for bioactivity by immersing the samples in simulated body fluid environment. The
      results obtained ascertained that SLS-fabricated scaffolds have good potential
      for TE applications.

PMID- 15516873
TI  - Relation between in vitro and in vivo osteogenic potential of cultured human bone
      marrow stromal cells.
AB  - The use of cell therapies in bone reconstruction has been the subject of
      extensive research. It is known that human bone marrow stromal cell (HBMSC)
      cultures contain a population of progenitor cells capable of differentiation
      towards the osteogenic lineage. In the present study, the correlation between the
      in vitro osteogenic potential of HBMSC cultures and their capacity to form bone
      in vivo was investigated. HBMSC cultures were established from 14 different
      donors. Fourth passage cells were examined for the expression of alkaline
      phosphatase (ALP), procollagen I (PCI) and osteopontin (OP), through flow
      cytometry and the effect of the osteogenic differentiation factor dexamethasone
      (Dex) on this expression was evaluated. In addition, the capacity of the cultures
      to induce in vivo bone formation was analysed by culturing the cells on porous
      hydroxyapatite (HA) scaffolds followed by subcutaneous implantation of these
      constructs in nude mice. Results showed expression of PCI, OP and ALP in all
      cultures, irrespective of the presence of Dex in the culture medium. Dex failed
      to have a significant effect on the expression of PCI and OP but it induced a
      consistent increase in the relative amount of cells expressing ALP. Nevertheless,
      although in vitro testing clearly indicated osteogenic potential in all cultures,
      HBMSC from six of the 14 tested donors did not form bone in vivo. The results,
      therefore, demonstrate that neither the expression of PCI, OP and ALP nor the
      absolute increase in Dex-stimulated ALP expression can as yet be used as
      predictive markers for in vivo bone formation by HBMSC. However, preliminary data
      indicate that not the absolute, but the relative increase in the percentage of
      ALP expressing cells caused by Dex stimulation may be related to the ability of
      the HBMSC to form bone.

PMID- 15516874
TI  - Strontium substituted calcium phosphate biphasic ceramics obtained by a powder
      precipitation method.
AB  - Strontium (Sr) substituted calcium phosphate ceramics were fabricated using a
      powder precipitation method. The Sr ions were added up to 8 mol % to replace the
      Ca ions during the powder preparation. Composition analysis showed that the added
      Sr was not fully incorporated within the as-precipitated apatite structure,
      presumably being washed out during the powder preparation. After calcination, the
      Sr containing powders were crystallized into apatite and tricalcium phosphate
      (TCP), that is, biphasic calcium phosphates were formed. The amount of TCP
      increased with increasing the Sr addition. The lattice parameters of the calcined
      powders increased gradually with Sr substitution in both the a- and c-axis.
      However, the obtained values deviated slightly from the calculated ones at higher
      Sr additions (>4%) due to the partial substitution of Sr ions. The microstructure
      of the sintered bodies changed with the Sr addition due to the formation of TCP.
      The Vickers hardness increased slightly from 5.2 to 5.5 MPa with increasing Sr
      addition, which was driven by the HA+TCP biphasic formation. The osteoblast-like
      cells cultured on the Sr-substituted biphasic sample spread and grew actively.
      The proliferation rate of the cells was higher in the samples containing more Sr.
      The alkaline phosphate activity of the cells was expressed to a higher degree
      with increasing Sr addition. These observations confirmed the enhanced cell
      viability and differentiation of the Sr-substituted biphasic calcium phosphate
      ceramics.

PMID- 15516875
TI  - Comparative investigation of the biocompatibility of various silicon nitride
      ceramic qualities in vitro.
AB  - There is a controversy about the biocompatibility of silicon nitride ceramics
      contained in the literature, which appears to be related to a factor of the
      individual chemical composition of different qualities of silicon nitride
      ceramics and of the different surface properties. This study attempts to
      investigate the cytotoxicity of different qualities of industrial silicon nitride
      ceramics applying an L929-cell culture model in a direct contact assay combined
      with a cell viability assessment. Five different qualities of industrial standard
      silicon nitride ceramics were chosen for in vitro testing. The chemical
      composition was determined by EDS analysis. Different biomedically approved
      aluminium oxide qualities, a titanium alloy, glass and polyvinylchloride (PVC)
      served as control materials. L929 mice fibroblasts were incubated directly on the
      materials for 24 h, stained with bisbenzimide and propidium iodine for double
      fluorochromasia viability testing, and evaluated by inversion-fluorescence
      microscopy to control cell morphology, viability and cell counts compared to
      empty well values. Scanning electron microscopy was applied to additionally
      investigate cell morphology. There was no observation of cytotoxic effects on the
      silicon nitride ceramic samples; moreover cell morphology remained the same as on
      aluminium oxide and titanium. Viability testing revealed the presence of avital
      cells exclusively on PVC, which served as a negative control. Cell counts on all
      polished surfaces showed significantly higher numbers, whereas some rough surface
      samples showed significantly lower numbers. We conclude that silicon nitride
      ceramics show no cytotoxic effects and should be considered for biomedical
      application owing to its favourable physiochemical properties, especially its
      superior resistance to mechanical stress, which would be useful for compression
      loaded conditions. Polished surfaces would appear to promote advanced
      biocompatibility.

PMID- 15516876
TI  - Improved mechanical properties of HIPS/hydroxyapatite composites by surface
      modification of hydroxyapatite via in-situ polymerization of styrene.
AB  - High impact polystyrene (HIPS)/hydroxyapatite (HA) composites are potential
      biomaterials for bone replacements due to their good biocompatibility and
      adequate mechanical properties. At the present work, the surface of the micron
      sized hydroxyapatite (HA) particles was modified by in situ polymerization of
      styrene (St), then compounded with HIPS. The effect of the modification of HA
      surface on morphology and mechanical properties of HIPS/HA composites were
      investigated. The results showed that the HA particles does not inhibit the
      polymerization of St. The PS segments coated on the HA surface by in situ
      polymerization of St enhances the compatibility between HA and HIPS, improves the
      dispersion of HA particles in HIPS matrix, and enhances the interfacial adhesion
      between HA and matrix. Thereby, the stiffness, tensile strength and notch impact
      strength of HIPS/HA composites are improved at the same time. And there is a
      critical coating thickness of PS on the HA surface for the optimum mechanical
      properties of HIPS/HA composites.

PMID- 15516877
TI  - Effect of particle morphology and polyethylene molecular weight on the fracture
      toughness of hydroxyapatite reinforced polyethylene composite.
AB  - Fracture toughness testing has been performed on hydroxyapatite-polyethylene
      composites. Sintered and unsintered grades of hydroxyapatite and two grades of
      high-density polyethylene were used to make 40 vol % hydroxyapatite composites.
      Compact tension testing was performed at both room temperature and at 37 degrees
      C and at three strain rates. The effect of increasing the loading rate from 2 to
      200 microm s(-1) was to increase the fracture toughness. Increasing the testing
      temperature or decreasing the surface area of the reinforcing particles also
      increased the fracture toughness. However, using a lower molecular weight,
      injection moulding, grade of polyethylene reduced the fracture toughness. Thus
      for higher fracture toughness, a low surface area sintered hydroxyapatite in a
      high-molecular weight polyethylene is required.

PMID- 15516878
TI  - The controlled resorption of porous alpha-tricalcium phosphate using a
      hydroxypropylcellulose coating.
AB  - Tricalcium phosphate (TCP) ceramic is known in orthopedics to be a bioresorbable
      bone substitute. A porous TCP ceramic body also has high potential as a drug
      delivery system in bony defects. Porous alpha-TCP ceramic can be easily
      fabricated using conventional sintering of beta-TCP, since alpha-TCP is the
      thermodynamically stable phase at temperatures above 1 100 degrees C. However,
      the solubility of alpha-TCP is much higher than that of beta-TCP. Therefore, the
      dissolution of porous alpha-TCP progresses at a higher rate than bone repair. In
      the present study, we attempted to reduce the dissolution rate of porous alpha
      TCP by employing an organic polymer coating. We fabricated porous alpha-TCP
      ceramic with a continuous 10-50 microm diameter pore structure by sintering a
      body made from a beta-TCP and potato starch slurry. The porous body obtained was
      coated with hydroxypropylcellulose (HPC), and then subjected to heat treatment.
      The chemical durability and mechanical properties of the body were examined
      before and after coating with the HPC. The dissolution of porous alpha-TCP in
      buffered solutions was reduced by coating with HPC and drying at 60 degrees C.
      The compressive strength of the porous alpha-TCP was also improved by coating
      with HPC. The results of in vivo experiments showed that some parts of the porous
      alpha-TCP ceramic coated with HPC remained in the canal of the tibia of a rabbit
      four weeks after implantation, whereas no residual was observed in a non-coated
      alpha-TCP ceramic. Coating with HPC was found to be effective for controlling
      bioresorption and improving the workability of porous alpha-TCP ceramic. The
      prepared porous alpha-TCP ceramic is expected to be useful as a novel material
      for bone fillers by incorporating it with drugs or osteoinductive factors.

PMID- 15516879
TI  - Endothelial cell alignment on cyclically-stretched silicone surfaces.
AB  - Endothelial cells at the interface between the bloodstream and the vessel wall
      are continuously subjected to mechanical stimulation in vivo, and it widely
      recognised that such stimulation plays an important role in cardiovascular
      physiology. Cell deformation is induced by mechanical forces such as cyclic
      stretch, fluid shear stress, and transmural pressure. Although much of the work
      in this field has dealt with the effect of fluid shear stress, very little is
      known about how cyclic forces modulate and alter the morphology of single
      endothelial cells, and thereafter, how they effect the confluent layer of
      endothelial cells lining the vessel wall. The aim of this study is to investigate
      the response of endothelial cells when subjected to substrate deformation of
      similar magnitude to those experienced in vivo. Human umbilical vein endothelial
      cells (HUVEC) were cultured on plasma-treated silicone strips and uni-axially
      cyclically stretched using a custom made mechanical device. Results showed that
      endothelial cells subject to 10% deformation for as little as 4 h reoriented
      perpendicular to the stretch direction. In addition, although no integrin coating
      was applied to the substrate, it was found that plasma-treated silicone provided
      a cell adhesion substrate comparable to the commonly used collagen type I. Thus
      the results show that the stretch stimulus alone affects the morphology of
      endothelial cells. Further studies are required to establish the relative
      importance of substrate strain vs. fluid flow stimuli.

PMID- 15516881
TI  - Safe sedation in pediatric neuroradiology: an impossible objective?

PMID- 15516880
TI  - Injectable bioactive glass/biodegradable polymer composite for bone and cartilage
      reconstruction: concept and experimental outcome with thermoplastic composites of
      poly(epsilon-caprolactone-co-D,L-lactide) and bioactive glass S53P4.
AB  - Injectable composites (Glepron) of particulate bioactive glass S53P4 (BAG) and
      Poly(epsilon-caprolactone-co-D,L-lactide) as thermoplastic carrier matrix were
      investigated as bone fillers in cancellous and cartilagineous subchondral bone
      defects in rabbits. Composites were injected as viscous liquid or mouldable
      paste. The glass granules of the composites resulted in good osteoconductivity
      and bone bonding that occurred initially at the interface between the glass and
      the host bone. The bone bioactivity index (BBI) indicating bone contacts between
      BAG and bone, as well as the bone coverage index (BCI) indicating bone ongrowth,
      correlated with the amount of glass in the composites. The indices were highest
      with 70 wt % of BAG, granule size 90-315 microm and did not improve by the
      addition of sucrose as in situ porosity creating agent in the composite or by
      using smaller (<45 microm) glass granules. The percentage of new bone ingrowth
      into the composite with 70 wt % of BAG was 6-8% at 23 weeks. At the articular
      surface cartilage regeneration with chondroblasts and mature chondrocytes was
      often evident. The composites were osteoconductive and easy to handle with short
      setting time. They were biocompatible with low foreign body cellular reaction.
      Results indicate a suitable working concept as a filler bone substitute for
      subchondral cancellous bone defects.

PMID- 15516882
TI  - SIAARTI-SARNePI Guidelines for sedation in pediatric neuroradiology.

PMID- 15516883
TI  - Low perioperative mortality for cardiac surgery in octogenarians.
AB  - AIM: The number of cardiac operations in octogenarians is steadily increasing. A
      review of personal 4 years' experience is made in order to identify which
      variables are associated to a poor prognosis in this high risk population.
      METHODS: Perioperative variables and short-term outcome of 109 consecutive
      octogenarians were prospectively collected in a database. Data were analysed with
      descriptive statistics. Univariate and multivariate analyses were performed to
      identify preoperative risk factors for prolonged mechanical ventilation and ICU
      stay. RESULTS: The 109 octogenarians represented 1.8% of the 4 940 cardiac
      operations performed at our University Teaching Hospital in the period January
      1998-June 2001: 94 patients had comorbidities (86%); 46 underwent valve surgery
      (42%), 38 had coronary artery bypass grafting surgery (36%), and combined
      procedures or aortic arch replacement were performed in 25 patients (22%). Two
      patients died (1.8%). Postoperative complications included: myocardial infarction
      (10 patients, 9%), stroke (6 patients, 5%), renal replacement therapy (1 patient,
      1%). Sixty nine patients (63%) had an uneventful perioperative period (63%). On a
      multivariate analysis, cardiopulmonary bypass (CPB) time was associated with
      prolonged intubation and ICU stay; mitral pathology predicted prolonged
      intubation while previous cardiac surgery was associated with prolonged ICU stay.
      CONCLUSION: The 109 octogenarians studied had an excellent course in the
      immediate postoperative period. Therefore, on the basis of personal experience
      cardiac surgery could be safely performed in octogenarians.

PMID- 15516884
TI  - Preemptive ketamine during general anesthesia for postoperative analgesia in
      patients undergoing laparoscopic cholecystectomy.
AB  - AIM: Preemptive analgesia is currently in use in the management of postoperative
      pain and no more under search. The administration of ketamine as intraoperative
      analgesic agent is well-known since a long time; the analgesic properties of this
      drug are related to its actions as a non-competitive N-methyl-D-aspartate
      receptors antagonist; these receptors present an excitatory function on pain
      transmission and this binding seems to prevent or reverse the central
      sensitisation of every kind of pain, including postoperative pain. In literature,
      the use of this anesthetic for the preemptive analgesia in the management of
      postoperative pain is controversial; for this reason the aim of our study was the
      clinical evaluation of preemptive perioperative analgesia with low-doses
      ketamine. METHODS: This trial involved 40 patients undergoing laparoscopic
      cholecystectomy, with the same surgical operator; postoperative analgesia was
      performed with the intraoperative administration of ketamine (0.7 mg/kg) or
      tramadol (15 mg/kg). A randomized, double-blind study was performed; after an
      inhalatory/analgesic general anesthesia (sevofluorane + remifentanyl) the
      postoperative-pain control was clinically evaluated through algometric
      measurements (Visual Analog Scale, Verbal Rating Scale, Pain Intensity
      Difference); supplemental doses of tramadol were administered if required, also
      to quantify the adequacy of analgesia, and adverse effects were evaluated.
      RESULTS: The results show that preemptive intraoperative analgesia with ketamine
      produces a good analgesia at the awakening, despite low duration (approximately 1
      hour), and upgrades the analgesic effect of tramadol in the postoperative period.
      Among the adverse effects, some (for example nausea) were related to the
      administration of both analgesics and to the kind of surgery, others
      (hallucinosis, nystagmus, photophobia, psychomotor excitation, psychotic
      symptoms) were due to ketamine, and others (respiratory depression and
      hypotension) could be related to tramadol. Although the adverse effects due to
      ketamine are more numerous than those related to tramadol, the second could
      potentially be more dangerous. CONCLUSION: Our study suggests that preemptive low
      doses ketamine is able to produce an adequate postoperative analgesia and
      increases the analgesic effect of tramadol; furthermore, ketamine adverse effects
      could be reduced by intraoperative administration of benzodiazepines and/or
      antiemetic drugs, or by the association of ketamine and a peripheral analgesic
      (ketorolac).

PMID- 15516885
TI  - Use of IgM and IgA-enriched immunoglobulins in the treatment of severe sepsis and
      septic shock. Clinical experience.
AB  - AIM: The aim of this study was to evaluate if the currently available clinical
      data and the time elapsing from the diagnosis to the administration of IgM and
      IgA-enriched immunoglobulins can predict the outcome of patients with severe
      sepsis and septic shock not responding to the current treatments. METHODS: All
      patients with these diagnoses, who did not respond to the standard treatment from
      August 1999 to September 2002, were retrospectively enrolled in the study. The
      variables evaluated included: (a) SAPS II and age at admission; (b) body
      temperature, mean arterial pressure, PaO2/FIO2 ratio, creatinine, blood white
      cell count on the day before the administration of the IgM and IgA-enriched
      immuno-globulins; (c) sequential organ failure assessment (SOFA) score before and
      during the treatment; (d) time elapsing between the diagnosis and the treatment;
      (e) outcome. RESULTS: Overall, 22 patients have been enrolled (17 M, 5 F, age
      54.3+/-14.5 years). Eleven (50%) survived. None of the variables measured was
      different among survivors and nonsurvivors. Only the time elapsing from the
      diagnosis of severe sepsis and septic shock and the beginning of the treatment
      significantly differed among survivors and nonsurvivors (2.72 +/- 1.49 days vs
      7.45 +/- 3.41 days respectively, p<0.005). CONCLUSION: In patients with severe
      sepsis and septic shock the currently available clinical variables and severity
      score are not valuable in identifying those patients who could take the maximal
      advantage from the administration of the IgM and IgA-enriched immunoglobulins.
      Thus, their time of administration plays a major role in the treatment of septic
      patients unresponding to the conventional treatment.

PMID- 15516887
TI  - Withdrawal syndrome.

PMID- 15516886
TI  - Use of quinupristin/dalfopristin in a critical patient with a methicillin
      resistant Staphilococcus aureus infection.
AB  - The growing incidence of infections due to Gram-positive multiresistant germs has
      stimulated research into new drugs endowed with broader activity, that are useful
      in case of infections unresponsive to common antibiotics. The case of a 28-year
      old man infected with a methicillin resistant Staphylococcus aureus non responder
      to therapy with glycopeptide antibiotics is reported. At admission the patient
      presented a septic condition and required mechanical ventilation. Antibiotic
      therapy was immediately started with teicoplanin+meropenem. Blood culture and
      bronchial aspirate evidenced a methicillin resistant Staphylococcus aureus with
      high sensibility to glycopeptide antibiotics. Although this therapy produced a
      slight improvement in clinical condition and the patient was extubated, fever and
      leucocytosis associated with a BAL positive to methicillin resistant
      Staphylococcus aureus, in vitro susceptible to glycopeptides, persisted.
      Considering the possibility of a non-responder condition of the patient to
      glycopeptide antibiotics, quinupristin/dalfopristin was added. The streptogramin
      produced a quick improvement in clinical condition with resolution of sepsis and
      culture sterilization. The patient improved progressively and was discharged. In
      conclusion, in our experience the association quinupristin/dalfopristin was
      effective in the resolution of a critical methicillin resistant Staphylococcus
      aureus infection non responder to classical treatment with glycopeptide
      antibiotics that showed a high sensibility in vitro.

PMID- 15516890
TI  - Database draws attention to not-so-Nobel intentions.

PMID- 15516891
TI  - Scientists stumped by test that promises tailored treatment.

PMID- 15516893
TI  - Israeli researchers eye simple test for multiple sclerosis.

PMID- 15516894
TI  - Genetics may aggravate India's growing AIDS problem.

PMID- 15516895
TI  - Chiron flu flap suggests vaccine industry needs shot in the arm.

PMID- 15516897
TI  - Profile: David Ho.

PMID- 15516898
TI  - Eye in the sky.

PMID- 15516900
TI  - Translation of cancer immunotherapies.

PMID- 15516901
TI  - Translation of cancer immunotherapies.

PMID- 15516902
TI  - Active tissue factor in blood?

PMID- 15516905
TI  - New paradigms, animal models may lift antidepressant research.

PMID- 15516907
TI  - Can nicotine treat sepsis?

PMID- 15516908
TI  - Hypertension with a grain of salt.

PMID- 15516910
TI  - Transplantation tolerance: babies take the first step.

PMID- 15516911
TI  - Stem cells bank on ATM machine.

PMID- 15516912
TI  - Turning up the heat in the fat cell.

PMID- 15516913
TI  - Transporter of a malaria catastrophe.

PMID- 15516915
TI  - From plankton to pathogen recognition.

PMID- 15516917
TI  - From Pasteur to genomics: progress and challenges in infectious diseases.
AB  - Over the past decade, microbiology and infectious disease research have undergone
      the most profound revolution since the times of Pasteur. Genomic sequencing has
      revealed the much-awaited blueprint of most pathogens. Screening blood for the
      nucleic acids of infectious agents has blunted the spread of pathogens by
      transfusion, the field of antiviral therapeutics has exploded and technologies
      for the development of novel and safer vaccines have become available. The
      quantum jump in our ability to detect, prevent and treat infectious diseases
      resulting from improved technologies and genomics was moderated during this
      period by the greatest emergence of new infectious agents ever recorded and a
      worrisome increase in resistance to existing therapies. Dozens of new infectious
      diseases are expected to emerge in the coming decades. Controlling these diseases
      will require a better understanding of the worldwide threat and economic burden
      of infectious diseases and a global agenda.

PMID- 15516920
TI  - Materials science: lead-free at last.

PMID- 15516921
TI  - Lead-free piezoceramics.
AB  - Lead has recently been expelled from many commercial applications and materials
      (for example, from solder, glass and pottery glaze) owing to concerns regarding
      its toxicity. Lead zirconium titanate (PZT) ceramics are high-performance
      piezoelectric materials, which are widely used in sensors, actuators and other
      electronic devices; they contain more than 60 weight per cent lead. Although
      there has been a concerted effort to develop lead-free piezoelectric ceramics, no
      effective alternative to PZT has yet been found. Here we report a lead-free
      piezoelectric ceramic with an electric-field-induced strain comparable to typical
      actuator-grade PZT. We achieved this through the combination of the discovery of
      a morphotropic phase boundary in an alkaline niobate-based perovskite solid
      solution, and the development of a processing route leading to highly <001>
      textured polycrystals. The ceramic exhibits a piezoelectric constant d33 (the
      induced charge per unit force applied in the same direction) of above 300
      picocoulombs per newton (pC N(-1)), and texturing the material leads to a peak
      d33 of 416 pC N(-1). The textured material also exhibits temperature-independent
      field-induced strain characteristics.

PMID- 15516922
TI  - Sorting signals can direct receptor-mediated export of soluble proteins into
      COPII vesicles.
AB  - Soluble secretory proteins are first translocated across endoplasmic reticulum
      (ER) membranes and folded in a specialized ER luminal environment. Fully folded
      and assembled secretory cargo are then segregated from ER-resident proteins into
      COPII-derived vesicles or tubular elements for anterograde transport. Mechanisms
      of bulk-flow, ER-retention and receptor-mediated export have been suggested to
      operate during this transport step, although these mechanisms are poorly
      understood. In yeast, there is evidence to suggest that Erv29p functions as a
      transmembrane receptor for the export of certain soluble cargo proteins including
      glycopro-alpha-factor (gpalphaf), the precursor of alpha-factor mating pheromone.
      Here we identify a hydrophobic signal within the pro-region of gpalphaf that is
      necessary for efficient packaging into COPII vesicles and for binding to Erv29p.
      When fused to Kar2p, an ER-resident protein, the pro-region sorting signal was
      sufficient to direct Erv29p-dependent export of the fusion protein into COPII
      vesicles. These findings indicate that specific motifs within soluble secretory
      proteins function in receptor-mediated export from the ER. Moreover, positive
      sorting signals seem to predominate over potential ER-retention mechanisms that
      may operate in localizing ER-resident proteins such as Kar2p.

PMID- 15516923
TI  - Retinal network adaptation to bright light requires tyrosinase.
AB  - The visual system adjusts its sensitivity to a wide range of light intensities.
      We report here that mutation of the zebrafish sdy gene, which encodes tyrosinase,
      slows down the onset of adaptation to bright light. When fish larvae were
      challenged with periods of darkness during the day, the sdy mutants required
      nearly an hour to recover optokinetic behavior after return to bright light,
      whereas wild types recovered within minutes. This behavioral deficit was
      phenocopied in fully pigmented fish by inhibiting tyrosinase and thus does not
      depend on the absence of melanin pigment in sdy. Electroretinograms showed that
      the dark-adapted retinal network recovers sensitivity to a pulse of light more
      slowly in sdy mutants than in wild types. This failure is localized in the
      retinal neural network, postsynaptic to photoreceptors. We propose that retinal
      pigment epithelium (which normally expresses tyrosinase) secretes a modulatory
      factor, possibly L-DOPA, which regulates light adaptation in the retinal
      circuitry.

PMID- 15516924
TI  - Deletion of a conserved Il4 silencer impairs T helper type 1-mediated immunity.
AB  - Helper T cell differentiation involves silencing as well as activation of gene
      expression. We have identified a conserved silencer of the gene encoding
      interleukin 4 (Il4) marked by DNase I hypersensitivity (HS IV) and permissive
      chromatin structure in all helper T cells. Deletion of HS IV increased Il4 and
      Il13 transcription by naive T cells and led to T helper type 2 skewing in vitro.
      HS IV controlled Il4 silencing during T helper type 1 differentiation, as HS IV
      deficient T helper type 1 cells that expressed interferon-gamma also produced
      abundant interleukin 4 in vitro and in vivo. Despite mounting a vigorous
      interferon-gamma response, HS IV-deficient mice were more susceptible to
      Leishmania major infection than were wild-type littermate control mice, showing a
      critical function for Il4 silencing in T helper type 1-mediated immunity.

PMID- 15516925
TI  - Distinct T cell dynamics in lymph nodes during the induction of tolerance and
      immunity.
AB  - Induction of immunity and peripheral tolerance requires contacts between antigen
      bearing dendritic cells (DCs) and cognate T cells. Using real-time two-photon
      microscopy, we have analyzed the dynamics of CD8(+) T cells in lymph nodes during
      the induction of antigen-specific immunity or tolerance. At 15-20 h after the
      induction of immunity, T cells stopped moving and established prolonged
      interactions with DCs. In tolerogenic conditions, despite effective initial T
      cell activation and proliferation, naive T cells remained motile and established
      serial brief contacts with multiple DCs. Thus, stable DC-T cell interactions
      occur during the induction of priming, whereas brief contacts may contribute to
      the induction of T cell tolerance.

PMID- 15516926
TI  - Autoreactivity and allelic inclusion in a B cell nuclear transfer mouse.
AB  - Lymphocytes typically express only one functional antigen receptor, a restriction
      contributed to by allelic exclusion. Here we have analyzed B lymphocyte
      development in offspring of a mouse generated by nuclear transfer using a single
      donor B lymphocyte. In this mouse, all immunoglobulin alleles were inherited as
      found in the donor lymphocyte. This donor cell had two rearranged immunoglobulin
      light chain alleles, both directing the synthesis of light chains that could form
      functional antigen receptors, one of which was autoreactive. Progeny mice
      carrying this immunoglobulin light chain allele produced mature B cells, some of
      which continued to express the autoreactive receptor but required another
      rearrangement to rescue them from negative selection. Such receptor editing
      failed to destroy expression of one original light chain allele, thereby
      recreating dual receptor expression on these surviving B cells. We suggest that
      autoreactive antibodies in serum of mice and humans are due in part to such
      'passenger' receptors.

PMID- 15516927
TI  - Giant room-temperature magnetoresistance in single-crystal Fe/MgO/Fe magnetic
      tunnel junctions.
AB  - The tunnel magnetoresistance (TMR) effect in magnetic tunnel junctions (MTJs) is
      the key to developing magnetoresistive random-access-memory (MRAM), magnetic
      sensors and novel programmable logic devices. Conventional MTJs with an amorphous
      aluminium oxide tunnel barrier, which have been extensively studied for device
      applications, exhibit a magnetoresistance ratio up to 70% at room temperature.
      This low magnetoresistance seriously limits the feasibility of spintronics
      devices. Here, we report a giant MR ratio up to 180% at room temperature in
      single-crystal Fe/MgO/Fe MTJs. The origin of this enormous TMR effect is coherent
      spin-polarized tunnelling, where the symmetry of electron wave functions plays an
      important role. Moreover, we observed that their tunnel magnetoresistance
      oscillates as a function of tunnel barrier thickness, indicating that coherency
      of wave functions is conserved across the tunnel barrier. The coherent TMR effect
      is a key to making spintronic devices with novel quantum-mechanical functions,
      and to developing gigabit-scale MRAM.

PMID- 15516928
TI  - Giant tunnelling magnetoresistance at room temperature with MgO (100) tunnel
      barriers.
AB  - Magnetically engineered magnetic tunnel junctions (MTJs) show promise as non
      volatile storage cells in high-performance solid-state magnetic random access
      memories (MRAM). The performance of these devices is currently limited by the
      modest (< approximately 70%) room-temperature tunnelling magnetoresistance (TMR)
      of technologically relevant MTJs. Much higher TMR values have been theoretically
      predicted for perfectly ordered (100) oriented single-crystalline Fe/MgO/Fe MTJs.
      Here we show that sputter-deposited polycrystalline MTJs grown on an amorphous
      underlayer, but with highly oriented (100) MgO tunnel barriers and CoFe
      electrodes, exhibit TMR values of up to approximately 220% at room temperature
      and approximately 300% at low temperatures. Consistent with these high TMR
      values, superconducting tunnelling spectroscopy experiments indicate that the
      tunnelling current has a very high spin polarization of approximately 85%, which
      rivals that previously observed only using half-metallic ferromagnets. Such high
      values of spin polarization and TMR in readily manufactureable and highly
      thermally stable devices (up to 400 degrees C) will accelerate the development of
      new families of spintronic devices.

PMID- 15516929
TI  - Tissue plasminogen activator neurovascular toxicity is controlled by activated
      protein C.
AB  - Although thrombolytic effects of tissue plasminogen activator (tPA) are
      beneficial, its neurotoxicity is problematic. Here, we report that tPA
      potentiates apoptosis in ischemic human brain endothelium and in mouse cortical
      neurons treated with N-methyl-D-aspartate (NMDA) by shifting the apoptotic
      pathways from caspase-9 to caspase-8, which directly activates caspase-3 without
      amplification through the Bid-mediated mitochondrial pathway. In vivo, tPA
      induced cerebral ischemic injury in mice was reduced by intracerebroventricular
      administration of caspase-8 inhibitor, but not by caspase-9 inhibitor, in
      contrast to controls in which caspase-9 inhibitor, but not caspase-8 inhibitor,
      was protective. Activated protein C (APC), a serine protease with anticoagulant,
      anti-inflammatory and antiapoptotic activities, which is neuroprotective during
      transient ischemia and promotes activation of antiapoptotic mechanisms in brain
      cells by acting directly on endothelium and neurons, blocked tPA vascular and
      neuronal toxicities in vitro and in vivo. APC inhibited tPA-induced caspase-8
      activation of caspase-3 in endothelium and caspase-3-dependent nuclear
      translocation of apoptosis-inducing factor in NMDA-treated neurons and reduced
      tPA-mediated cerebral ischemic injury in mice. Data suggest that tPA shifts the
      apoptotic signal in stressed brain cells from the intrinsic to the extrinsic
      pathway which requires caspase-8. APC blocks tPA's neurovascular toxicity and may
      add substantially to the effectiveness of tPA therapy for stroke.

PMID- 15516930
TI  - Widespread occurrence of alternative splicing at NAGNAG acceptors contributes to
      proteome plasticity.
AB  - Splice acceptors with the genomic NAGNAG motif may cause NAG insertion-deletions
      in transcripts, occur in 30% of human genes and are functional in at least 5% of
      human genes. We found five significant biases indicating that their distribution
      is nonrandom and that they are evolutionarily conserved and tissue-specific.
      Because of their subtle effects on mRNA and protein structures, these splice
      acceptors are often overlooked or underestimated, but they may have a great
      impact on biology and disease.

PMID- 15516931
TI  - Imprinting on distal chromosome 7 in the placenta involves repressive histone
      methylation independent of DNA methylation.
AB  - Imprinted genes are expressed from only one of the parental chromosomes and are
      marked epigenetically by DNA methylation and histone modifications. The
      imprinting center 2 (IC2) on mouse distal chromosome 7 is flanked by several
      paternally repressed genes, with the more distant ones imprinted exclusively in
      the placenta. We found that most of these genes lack parent-specific DNA
      methylation, and genetic ablation of methylation does not lead to loss of their
      imprinting in the trophoblast (placenta). The silent paternal alleles of the
      genes are marked in the trophoblast by repressive histone modifications
      (dimethylation at Lys9 of histone H3 and trimethylation at Lys27 of histone H3),
      which are disrupted when IC2 is deleted, leading to reactivation of the paternal
      alleles. Thus, repressive histone methylation is recruited by IC2 (potentially
      through a noncoding antisense RNA) to the paternal chromosome in a region of at
      least 700 kb and maintains imprinting in this cluster in the placenta,
      independently of DNA methylation. We propose that an evolutionarily older
      imprinting mechanism limited to extraembryonic tissues was based on histone
      modifications, and that this mechanism was subsequently made more stable for use
      in embryonic lineages by the recruitment of DNA methylation.

PMID- 15516932
TI  - Imprinting along the Kcnq1 domain on mouse chromosome 7 involves repressive
      histone methylation and recruitment of Polycomb group complexes.
AB  - Imprinted genes are clustered in domains, and their allelic repression is
      mediated by imprinting control regions. These imprinting control regions are
      marked by DNA methylation, which is essential to maintain imprinting in the
      embryo. To explore how imprinting is regulated in placenta, we studied the Kcnq1
      domain on mouse distal chromosome 7. This large domain is controlled by an
      intronic imprinting control region and comprises multiple genes that are
      imprinted in placenta, without the involvement of promoter DNA methylation. We
      found that the paternal repression along the domain involves acquisition of
      trimethylation at Lys27 and dimethylation at Lys9 of histone H3. Eed-Ezh2
      Polycomb complexes are recruited to the paternal chromosome and potentially
      regulate its repressive histone methylation. Studies on embryonic stem cells and
      early embryos support our proposal that chromatin repression is established early
      in development and is maintained in the placenta. In the embryo, however,
      imprinting is stably maintained only at genes that have promoter DNA methylation.
      These data underscore the importance of histone methylation in placental
      imprinting and identify mechanistic similarities with X-chromosome inactivation
      in extraembryonic tissues, suggesting that the two epigenetic mechanisms are
      evolutionarily linked.

PMID- 15516933
TI  - Disseminated tuberculosis following reduced-intensity cord blood transplantation
      for adult patients with hematological diseases.
AB  - Allogeneic hematopoietic stem cell transplantation (allo-SCT) recipients are
      prone to infections. The incidences of mycobacterial infections after allo-SCT in
      several case series vary from less than 0.1-5.5%. However, no study has been
      published on tuberculosis following unrelated cord blood transplantation (UCBT).
      We retrospectively reviewed medical records of 113 adult patients with a median
      age of 54 years who underwent reduced-intensity UCBT (RI-UCBT) at Toranomon
      Hospital from March 2002 to May 2004. Mycobacterium tuberculosis infections were
      diagnosed in three patients (2.7%), of these two patients developed primary
      infection and one patient developed reactivation of latent tuberculosis. The
      interval between RI-UCBT and the diagnosis of tuberculosis was 34, 41 and 61
      days. All the patients had disseminated disease at diagnosis. Histological
      examination showed the lack of granuloma in caseous necrosis. Combination
      antituberculous treatments showed limited efficacy, and two patients died
      immediately after diagnosis. M. tuberculosis caused life-threatening illness,
      rapidly progressing in RI-UCBT recipients. The lack of granuloma in caseous
      necrosis suggests the impaired T-cell function in early post transplant phase of
      RI-UCBT. We should consider M. tuberculosis in the differential diagnoses of
      fever of unknown source after RI-UCBT.

PMID- 15516934
TI  - Appropriate busulfan dosing.

PMID- 15516935
TI  - Counting the cost: markers of endothelial damage in hematopoietic stem cell
      transplantation.
AB  - During hematopoietic stem cell transplantation (HSCT), endothelial damage is the
      pathological hallmark of veno-occlusive disease of the liver, thrombotic
      microangiopathy, capillary leak syndrome and graft-versus-host disease. Events
      prior to conditioning, the conditioning regimen itself as well as calcineurin
      inhibitors may all induce endothelial damage. Unfortunately, the relative
      importance of these factors and their interactions, the time frame of endothelial
      damage and individual susceptibility remain unknown. Moreover, it is conceivable
      that conditioning regimens differ markedly in their propensity to initiate
      endothelial damage. Monitoring endothelial damage and response to treatment is
      hampered by the current lack of suitable markers. In this regard, an ideal marker
      should be sensitive and specific and indicate the development of an endothelial
      disorder prior to the onset of symptoms and organ dysfunction. Soluble markers,
      such as thrombomodulin, are easily amenable with immunoassays; yet, the
      interpretation of their levels is hampered by the influence of comorbidity.
      Evaluation of circulating endothelial cells in HSCT demonstrated a marked and
      dose-dependent increase in cell numbers after conditioning. The challenge ahead
      is to establish and evaluate novel markers of endothelial damage to permit early
      detection of disease, monitor response to treatment and evaluate different
      conditioning regimens.

PMID- 15516936
TI  - Reduced-intensity conditioning regimen with thiotepa and fludarabine followed by
      allogeneic blood stem cell transplantation in haematological malignancies.
AB  - The aim of this study was to investigate thiotepa (TT) and fludarabine (Fluda) as
      a preparative regimen for allogeneic peripheral stem cell transplant in patients
      not eligible for a standard myeloablative regimen due to comorbidities and/or
      poor performance status. TT was given at a dose of 10 mg/kg over 2 days and Fluda
      at 125 mg/m(2) over 5 days. In all, 21 patients (14 male, seven female; 10 acute
      leukaemia, eight myelodysplastic syndrome, two non-Hodgkin's lymphoma, one
      Hodgkin's disease) were treated. The median age was 51 years (range 30-55 years).
      All patients achieved full donor-type chimaerism. Adverse events included mild
      nausea and vomiting in two patients and a slight increase of serum amylase in
      three. A total of 13 patients received RBC transfusions (median 6 U, range 1-23),
      and all received platelets (median 4 U, range 1-27). Four patients died of
      nonrelapse causes and five of relapse. The 1-year probabilities of transplant
      related mortality and relapse were 19 and 29%, respectively. In total, 12
      patients remain in complete remission (median follow-up: 786 days). The 3-year
      overall survival probability was 58%. We conclude that this regimen is feasible
      and well tolerated.

PMID- 15516937
TI  - Extramedullary vs medullary relapse after autologous or allogeneic hematopoietic
      stem cell transplantation (HSCT) in multiple myeloma (MM) and its correlation to
      clinical outcome.
AB  - Risk-adapted treatment of multiple myeloma (MM) includes autologous (auto-) and
      allogeneic (allo-) hematopoietic stem cell transplantation (HSCT). Case reports
      on extramedullary (EM) compared to bone marrow (BM) relapse after HSCT suggest a
      dismal prognosis. We compared the outcome of 78 MM patients relapsing after auto-
      (group A: n = 53) or allo- (group B: n = 25) HSCT, stratified into BM (64
      patients) vs EM (14 patients) relapse. The relapse-specific groups were also
      compared with respect to risk factors, including age, beta2-microglobulin,
      pretreatment, cytogenetics and stage. EM relapse sites were lungs (5), soft
      tissue (4), pericardium (2), bone (1), skin (1) and CNS (1). As of May 2004, the
      overall (OS) and progression-free (PFS) survival after HSCT in patients relapsing
      from EM sites was not significantly different from BM relapse patients, both
      after auto- and allo-HSCT. Although MM patients relapsing from EM sites after
      allo-HSCT used to be regarded as having few therapeutic options, we observed
      encouraging responses to donor lymphocyte infusions (DLI). Treatment responses to
      DLIs were observed in 5/9 (56%) BM relapse patients, and in 3/4 (75%) EM relapse
      patients. These observations suggest that EM relapse after HSCT is common and
      needs an individualized diagnostic and therapeutic approach in MM during clinical
      follow-up after HSCT.

PMID- 15516938
TI  - Loss of the GVL effect by loss of the Y-chromosome as putative mechanism of
      immune escape in ALL.

PMID- 15516939
TI  - Long-term follow-up of secondary malignancies in adults after allogeneic bone
      marrow transplantation.
AB  - The purpose of this study was to evaluate the estimated incidence of secondary
      malignancies post-allogeneic bone marrow transplantation (BMT) in a cohort of
      adult patients previously reported now with an additional 8.5 years of follow-up.
      A cohort of 557 patients older than age 16 years underwent allogeneic BMT between
      June 1970 and November 1993. Histologic reports confirmed the diagnosis of a
      secondary malignancy. Multivariate Cox proportional hazards method was utilized
      to investigate predictors for the development of secondary malignancies. In all,
      31 patients in this cohort developed a secondary malignancy a median of 6.79
      years after their transplant. The estimated cumulative incidence rate of
      secondary malignancy was 4.2% at 10 years post transplant. When compared to the
      general population, the estimated observed/expected ratio of new cancer diagnoses
      was 5.13. On multivariate analysis, older age at the time of transplant was the
      only significant predictor for development of secondary cancer (P=0.01). The most
      common malignancies observed were nonmelanomatous skin cancers and squamous cell
      cancers of the buccal cavity. The risk of developing a secondary malignancy after
      allogeneic BMT is significant, particularly in older patients. Long-term
      survivors of transplant require regular monitoring for early signs of cancer,
      particularly of the skin and oral cavity.

PMID- 15516940
TI  - First-line high-dose chemotherapy for patients with poor prognosis extragonadal
      germ cell tumors: the experience of the European Bone Marrow Transplantation
      (EBMT) Solid Tumors Working Party.
AB  - Extragonadal germ cell tumors are classified according to the staging system of
      the International Germ Cell Cancer Collaborative Group (IGCCCG). The 5-year
      overall and disease-free survival rates for poor prognosis patients are 41 and
      48%, respectively after standard-dose chemotherapy. We report the experience of
      the EBMT Solid Tumours Working Party (STWP) with first-line HDCT with
      hematopoietic progenitor cell support (HPCS) in patients with poor prognosis
      extragonadal nonseminomatous germ cell tumor (NSGCT). Between 1990 and 2001, 22
      extragonadal NSGCT patients (21 M, 1 F), median age 30 years (range 17-52) were
      treated with first-line HDCT with HPCS. Primary site was mediastinum in 11
      patients, retroperitoneum in 10, and unknown in one. The Carbopec regimen,
      consisting of high doses of carboplatin, etoposide, and cyclophosphamide, was
      used in most cases (12 patients). No treatment-related deaths occurred. No
      patient developed myelodysplasia or a secondary leukemia. In total, 17 of 22
      patients (77%) achieved complete remission. At a median follow-up of 50 months
      (range 26-132), 15 patients (68%) are alive disease-free. The survival rates of
      patients with poor prognosis extragonadal NSGCT treated with first-line HDCT in
      the EBMT STWP experience appear higher than that expected according to the IGCCCG
      classification.

PMID- 15516941
TI  - Successful transplantation of CD34+ selected peripheral blood stem cells from an
      unrelated donor in an adult patient with Diamond-Blackfan anemia and secondary
      hemochromatosis.

PMID- 15516942
TI  - A prospective randomized study of clinical and economic consequences of using G
      CSF following autologous peripheral blood progenitor cell (PBPC) transplantation
      in children.
AB  - This prospective and randomized study was conducted to evaluate clinical and
      economic consequences of using granulocyte colony-stimulating factor (G-CSF)
      following autologous peripheral blood progenitor cell (PBPC) transplantation in
      children. Between January 1999 and December 2003, 117 patients underwent
      autologous PBPCT: 51 patients received G-CSF following PBPCT, while 66 patients
      did not receive G-CSF. Median time to absolute neutrophil count > 0.5 x 10(9)/l
      was 10 days in the treatment group and 11 days in the control group (P < 0.009).
      The median time to platelets >20 x 10(9)/l was 12 days in both groups (P = NS).
      The median time to platelets >50 x 10(9)/l was 15 days in the G-CSF group and 14
      days in the control group (P<0.005). In patients who received <5 x 10(6)/kg CD34+
      cells, the median time to platelets >20 x 10(9)/l and >50 x 10(9)/l was similar
      with or without G-CSF (12 and 15 days, respectively). Platelet transfusion
      requirements were lower in the control group (2 vs 3 U in G-CSF group). There was
      a trend towards higher total costs with G-CSF: 8146.82 Euros and 7873.34 Euros
      with and without G-CSF, respectively (P = 0.1). Our data suggest that there is no
      indication of the standard application of G-CSF in children following PBPC
      transplantation. The only possible indication is the group of patients with a
      lower yield of CD34+ cells.

PMID- 15516943
TI  - Engraftment syndrome after autologous peripheral blood progenitor cell
      transplantation in pediatric patients: a prospective evaluation of risk factors
      and outcome.
AB  - We prospectively analyzed the incidence, risk factors and outcome of engraftment
      syndrome (ES) in 112 patients undergoing autologous peripheral blood progenitor
      cell transplantation with different malignancies between January 1999 and
      December 2003. The median age was 8 years (range 1-18). There were 73 males.
      There were 37 hematological neoplasias and 75 solid tumors. Disease status at
      transplantation was early in 49, intermediate in 15 and 48 in advanced phase. The
      median CD34+ cells infused was 4.6 x 10(6)/kg. With a median follow-up of 23
      months (1-116 months), 38 patients developed ES. The cumulative incidence of ES
      was 34.5 +/- 4.5% and the event-free survival was 58.3 +/- 12%. There were no
      differences in the causes of death between patients with or without ES. A high
      number of CD34+ cells/kg infused, patients transplanted in early phase, the type
      of malignancy (solid tumor) and conditioning regimens other than busulfan based
      were significantly associated with ES in a multivariate analysis.

PMID- 15516944
TI  - In vivo Campath for the prevention of GvHD following allogeneic HSCT: effects of
      dose, schedule and antibody type.

PMID- 15516945
TI  - Risk-adjusted manipulation of melphalan dose before stem cell transplantation in
      patients with amyloidosis is associated with a lower response rate.
AB  - High-dose chemotherapy and autologous stem cell transplantation are used
      increasingly to treat patients with light-chain-related amyloidosis (AL).
      Treatment-related mortality is approximately 15%. To enable more patients to
      undergo stem cell transplantation, a risk-adapted strategy has been developed to
      treat with lower chemotherapy doses those patients who are at excessive risk. It
      is unclear whether reducing the chemotherapy dose in patients at excessive risk
      of treatment toxicity reduces the overall response. We retrospectively reviewed
      171 AL patients who underwent conditioning chemotherapy with stem cell
      transplantation. The patients comprised two groups: those receiving standard high
      dose melphalan and those receiving intermediate-dose melphalan. Responses were
      categorized as hematologic response, which used criteria for myeloma response.
      The two groups showed statistically significant differences; the overall response
      rates were 75% in the high-dose group and 53% in the intermediate-dose group
      although treatment-related mortality was the same in both groups. Reducing the
      melphalan dose appeared to render more AL patients eligible for stem cell
      transplantation but sacrificed an element of response. Methods are needed to
      reduce treatment-related toxicity so that more patients can receive full-dose
      conditioning chemotherapy.

PMID- 15516946
TI  - Outcome of hematopoietic stem cell transplantation in patients with atypical
      chronic myeloid leukemia.
AB  - Atypical chronic myeloid leukemia (aCML) occurs rarely and is associated with a
      poor prognosis when treated with conventional chemotherapy. We evaluated the
      outcome of aCML after allogeneic hematopoietic stem cell transplantation (HSCT).
      Nine patients were transplanted from HLA-identical siblings (n = 4), HLA
      compatible unrelated donors (n = 4) or twin brother (n = 1). Median follow-up was
      55 months after transplant (range, 9.1-118.1 months). One patient who was
      transplanted in advanced disease with bone marrow from his twin brother relapsed
      19 months post transplant. This patient was successfully retransplanted from the
      original donor. All patients remained in complete remission. Analysis of the
      leukocyte chimerism of peripheral white blood cells and bone marrow buffy coat
      cells by VNTR-polymerase chain reaction (PCR) and single-nucleotide polymorphism
      real-time PCR revealed complete chimerism in all patients who had received an
      allogeneic transplant. One patient suffering from cerebral toxoplasmosis died 9
      months post transplant. All other patients were alive at the time of analysis.
      Our findings suggest that the outcome of allogeneic or syngeneic transplantation
      in patients with aCML may not be worse than the outcome of transplantation for
      BCR-ABL-positive CML.

PMID- 15516947
TI  - Authorship without authorization.

PMID- 15516948
TI  - New approaches to biomaterials design.
AB  - The adoption of combinatorial and computational methods in biomaterials design is
      a highway towards the discovery and realization of tailored polymeric materials
      to satisfy the specific requirements of many diverse biomedical or prosthetic
      applications.

PMID- 15516951
TI  - Mixing superconductivity and magnetism.

PMID- 15516952
TI  - Welding and patterning in a flash.

PMID- 15516953
TI  - Relaxing times for silicon.

PMID- 15516955
TI  - The myth and magic of plastic.

PMID- 15516956
TI  - Quasicrystals as cluster aggregates.
AB  - Quasicrystals are solids that exhibit symmetries long thought forbidden in
      nature. Since their discovery in a rapidly solidified Al-Mn alloy in 1984, the
      central issue in the field has been to understand why they form. Are they
      energetically stable compounds or stabilized by entropy? In recent years, major
      strides have been made in determining atomic structure, largely by direct imaging
      using advanced electron microscopy. One system is now known to be energetically
      stabilized, and quasicrystals are therefore firmly established as a new physical
      state of matter. They represent a unique packing of atomic clusters some tens of
      atoms in size, with substantial localized fluctuations, referred to as phasons.
      Understanding phasons may in future allow their unique macroscopic properties to
      be tailored for useful materials applications.

PMID- 15516957
TI  - Friends or foes - bipolar effects of the tumour stroma in cancer.
AB  - The restricted view of tumour progression as a multistep process defined by the
      accumulation of mutations in cancer cells has largely ignored the substantial
      contribution of the tumour microenvironment to malignancy. Even though the seed
      and soil hypothesis of Paget dates to 1889, it has been less than two decades
      since researchers have included the tumour microenvironment in their analyses of
      tumour progression. What have we recently learned from studying tumour-stroma
      interactions, and will this help to define new targets for therapy?

PMID- 15516958
TI  - Association studies for finding cancer-susceptibility genetic variants.
AB  - Cancer is the result of complex interactions between inherited and environmental
      factors. Known genes account for a small proportion of the heritability of
      cancer, and it is likely that many genes with modest effects are yet to be found.
      Genetic-association studies have been widely used in the search for such genes,
      but success has been limited so far. Increased knowledge of the function of genes
      and the architecture of human genetic variation combined with new genotyping
      technologies herald a new era of gene mapping by association.

PMID- 15516959
TI  - Antitumour effects of antiretroviral therapy.
AB  - Infection by human immunodeficiency virus (HIV) is associated with an increased
      risk of certain tumours, particularly Kaposi's sarcoma, non-Hodgkin's lymphomas
      and cervical cancer. However, the incidence of these tumours in HIV-infected
      patients has decreased significantly since the widespread use of highly active
      antiretroviral therapy (HAART). This effect cannot be solely explained by the
      ability of these drugs to suppress HIV replication and thereby reconstitute the
      immune system. Recent studies have shown that inhibitors of the HIV aspartyl
      protease, which are widely used in HAART, have direct anti-angiogenic and
      antitumour effects that are unrelated to their antiviral activity. So these drugs
      might be used to treat cancer in patients who are not infected with HIV.

PMID- 15516960
TI  - The emerging roles of human tissue kallikreins in cancer.
AB  - Human tissue kallikreins (hKs), which are encoded by the largest contiguous
      cluster of protease genes in the human genome, are secreted serine proteases with
      diverse expression patterns and physiological roles. Although primarily known for
      their clinical applicability as cancer biomarkers, recent evidence implicates hKs
      in many cancer-related processes, including cell-growth regulation, angiogenesis,
      invasion and metastasis. They have been shown to promote or inhibit neoplastic
      progression, acting individually and/or in cascades with other hKs and proteases,
      and might represent attractive targets for therapeutic intervention.

PMID- 15516961
TI  - Why do cancers have high aerobic glycolysis?
AB  - If carcinogenesis occurs by somatic evolution, then common components of the
      cancer phenotype result from active selection and must, therefore, confer a
      significant growth advantage. A near-universal property of primary and metastatic
      cancers is upregulation of glycolysis, resulting in increased glucose
      consumption, which can be observed with clinical tumour imaging. We propose that
      persistent metabolism of glucose to lactate even in aerobic conditions is an
      adaptation to intermittent hypoxia in pre-malignant lesions. However,
      upregulation of glycolysis leads to microenvironmental acidosis requiring
      evolution to phenotypes resistant to acid-induced cell toxicity. Subsequent cell
      populations with upregulated glycolysis and acid resistance have a powerful
      growth advantage, which promotes unconstrained proliferation and invasion.

PMID- 15516962
TI  - The CXCL12-CXCR4 chemotactic pathway as a target of adjuvant breast cancer
      therapies.
AB  - Dose-dense adjuvant breast cancer chemotherapy is a new treatment strategy that
      aims to improve tumour control by using more frequent cytotoxic dosing together
      with continuous granulocyte colony-stimulating factor (G-CSF) to minimize
      neutropaenia. In addition to stimulating neutrophil proliferation, G-CSF
      mobilizes neutrophils from the bone marrow through proteolytic disruption of the
      chemokine receptor CXCR4 and its chemotactic ligand CXCL12. As breast cancers
      also express CXCR4 and oestrogen induces CXCL12, the success of dose-dense
      treatment could partly reflect inhibition of CXCR4-dependent micrometastatic
      homing and/or paracrine survival, and suggests a benefit of adjuvant oestrogen
      suppression for patients with oestrogen-receptor-negative, CXCR4-positive
      disease.

PMID- 15516963
TI  - Opportunities for cancer epidemiology in developing countries.
AB  - Most cancer epidemiology studies involve people living in North America and
      Europe, which represent only a fraction of the global population. The wide
      variety of dietary, lifestyle and environmental exposures, as well as the genetic
      variation among people in developing countries can provide valuable new
      information on factors that contribute to cancer or that protect against it. What
      are the challenges and advantages to performing large epidemiological studies in
      developing nations?

PMID- 15516964
TI  - Regulatory T cells: friend or foe in immunity to infection?
AB  - Homeostasis in the immune system depends on a balance between the responses that
      control infection and tumour growth and the reciprocal responses that prevent
      inflammation and autoimmune diseases. It is now recognized that regulatory T
      cells have a crucial role in suppressing immune responses to self-antigens and in
      preventing autoimmune diseases. Evidence is also emerging that regulatory T cells
      control immune responses to bacteria, viruses, parasites and fungi. This article
      explores the possibility that regulatory T cells can be both beneficial to the
      host, through limiting the immunopathology associated with anti-pathogen immune
      responses, and beneficial to the pathogen, through subversion of the protective
      immune responses of the host.

PMID- 15516965
TI  - Strategies to enhance T-cell reconstitution in immunocompromised patients.
AB  - Immune deficiency, together with its associated risks such as infections, is
      becoming an increasingly important clinical problem owing to the ageing of the
      general population and the increasing number of patients with HIV/AIDS,
      malignancies (especially those treated with intensive chemotherapy or
      radiotherapy) or transplants (of either solid organs or haematopoietic stem
      cells). Of all immune cells, T cells are the most often affected, leading to a
      prolonged deficiency of T cells, which has important clinical consequences.
      Accordingly, strategies to improve the recovery and function of T cells, as we
      discuss here, should have a direct impact on reducing the morbidity and mortality
      of many patients and should increase the efficacy of therapeutic and prophylactic
      vaccinations against microbial pathogens or tumours.

PMID- 15516966
TI  - Retroviral restriction by APOBEC proteins.
AB  - A powerful mechanism of vertebrate innate immunity has been discovered in the
      past year, in which APOBEC proteins inhibit retroviruses by deaminating cytosine
      residues in nascent retroviral cDNA. To thwart this cellular defence, HIV encodes
      Vif, a small protein that mediates APOBEC degradation. Therefore, the balance
      between APOBECs and Vif might be a crucial determinant of the outcome of
      retroviral infection. Vertebrates have up to 11 different APOBEC proteins, with
      primates having the most. APOBEC proteins include AID, a probable DNA mutator
      that is responsible for immunoglobulin-gene diversification, and APOBEC1, an RNA
      editor with antiretroviral activities. This APOBEC abundance might help to tip
      the balance in favour of cellular defences.

PMID- 15516967
TI  - Clinical strategies for expansion of haematopoietic stem cells.
AB  - Haematopoietic stem cells (HSCs) give rise to all blood and immune cells and are
      used in clinical transplantation protocols to treat a wide variety of diseases.
      The ability to increase the number of HSCs either in vivo or in vitro would
      provide new treatment options, but the amplification of HSCs has been difficult
      to achieve. Recent insights into the mechanisms of HSC self-renewal now make the
      amplification of HSCs a plausible clinical goal. This article reviews the
      molecular mechanisms that control HSC numbers and discusses how these can be
      modulated to increase the number of HSCs. Clinical applications of HSC expansion
      are then discussed for their potential to address the current limitations of HSC
      transplantation.

PMID- 15516968
TI  - Forkhead-box transcription factors and their role in the immune system.
AB  - It is more than a decade since the discovery of the first forkhead-box (FOX)
      transcription factor in the fruit fly Drosophila melanogaster. In the intervening
      time, there has been an explosion in the identification and characterization of
      members of this family of proteins. Importantly, in the past few years, it has
      become clear that members of the FOX family have crucial roles in various aspects
      of immune regulation, from lymphocyte survival to thymic development. This review
      focuses on FOXP3, FOXN1, FOXJ1 and members of the FOXO subfamily and their
      function in the immune system.

PMID- 15516969
TI  - Recent developments in the transcriptional regulation of cytolytic effector
      cells.
AB  - Transcription factors have a profound influence on both the differentiation and
      effector function of cells of the immune system. T-bet controls the cytotoxicity
      of CD8(+) T cells and the production of interferon-gamma, and it also affects the
      development and function of natural killer cells and natural killer T cells.
      Other factors such as eomesodermin, MEF, ETS1 and members of the interferon
      regulatory factor family also contribute to the effector function of immune
      cells. In this review, we focus on recent studies that have shed light on the
      transcriptional mechanisms that regulate cellular effector function in the immune
      system.

PMID- 15516970
TI  - Complementary and alternative medicine: assessing the evidence for immunological
      benefits.
AB  - With words such as AIDS, allergy and autoimmunity embedded in the popular
      lexicon, we often equate health with the precision and the tenor of responses to
      allergens and microorganisms. This leads many people to seek their own solutions
      to sustain, restore or even boost their immune competence, hoping to live more
      comfortably and longer. Here, we consider the social and clinical contexts in
      which these promises of enhanced immunity are pursued through popular practices
      known as complementary and alternative medicine and the evidence that supports
      these.

PMID- 15516971
TI  - Oligoclonal T cells in histiocytic necrotizing lymphadenopathy are associated
      with TLR9+ plasmacytoid dendritic cells.
AB  - Histiocytic necrotizing lymphadenopathy (HNL), a disease of unknown cause, is
      characterized pathologically by the presence of plasmacytoid dendritic cells
      (pDCs), which are frequently mixed with oligoclonal T cells (OTCs) and myeloid
      cells. Toll-like receptors (TLRs 1-10) are a family of pattern recognition
      receptors of DCs. To investigate the interactions between pDCs and T cells, and
      to look for an etiology of HNL, we studied 24 HNLs for the profile of TLRs.
      Transcripts of TLR7, a receptor on pDCs for single-stranded RNA, were found in
      every case, confirming the universal presence of pDCs. Transcripts of TLR9,
      another receptor on pDCs for microbial unmethylated CpG-rich DNA, were correlated
      with OTCs, implying T-cell expansion stimulated by TLR9+ pDCs in response to a
      microbe. Because PCRs for bacterial 16S rDNAs were negative in the lymph nodes, a
      bacterial origin seems unlikely, but a virus remains a possible candidate. The
      pDCs lacked the maturation marker CD83, which suggested ineffective stimulation
      of T cells and might account for the usually benign course of HNL. Taken
      together, these data illustrate a novel approach, based upon TLR transcript
      analysis, for the integration of pathology, immunology, and clinical findings of
      HNL.

PMID- 15516972
TI  - Prognostic implication of laminin-5 gamma 2 chain expression in the invasive
      front of colorectal cancers, disclosed by area-specific four-point tissue
      microarrays.
AB  - The laminin-5 gamma 2 chain (LN-5gamma2) is known to be a marker of invasion in
      several cancer types. Our purpose was to examine the prognostic significance of
      LN-5gamma2 expression in different areas of individual colorectal cancers (CRCs)
      by using tissue microarrays (TMAs), and to clarify the optimal areas for
      prognostic assessment. Using formalin-fixed paraffin-embedded tissue blocks of
      pT3 primary CRCs resected from 120 patients, we constructed TMA blocks of tissue
      core specimens taken from the submucosal invasive front, subserosal invasive
      front, central area, and rolled edge of each tumor. Using these four-point TMA
      sets, cytoplasmic LN-5gamma2 expression was immunohistochemically surveyed, and
      the area-specific prognostic significance of LN-5gamma2 expression was evaluated.
      The data revealed that 35, 30, 15 and 10% of the 120 CRCs showed high-grade LN
      5gamma2 expression in the submucosal invasive front, subserosal invasive front,
      central area and rolled edge, respectively. Disease-specific survival curves for
      the groups with high- and low-grade LN-5gamma2 in the submucosal invasive front
      and subserosal invasive front were different significantly or of marginal
      difference (respective 5-year survival rates: 54 and 78% for submucosal invasive
      front (P=0.030) and 58 and 75% for subserosal invasive front (P=0.055)).
      Multivariate analysis revealed that the grades of LN-5gamma2 expression in
      submucosal invasive front (hazard ratio=2.0, P=0.047) and subserosal invasive
      front (hazard ratio=2.9, P=0.0033) were independent prognostic factors. In
      contrast, the grades of LN-5gamma2 expression in the central area and rolled edge
      did not have a significant impact on patient prognosis. Analysis using area
      specific four-point TMAs clearly demonstrated that LN-5gamma2 expression in the
      invasive front largely influences the degree of clinical aggressiveness of CRC
      and its tendency to metastasize.

PMID- 15516973
TI  - Autocrine activation of an osteopontin-CD44-Rac pathway enhances invasion and
      transformation by H-RasV12.
AB  - Activated forms of Ras family members are prevalent in many cancers where Ras
      mutants transduce signals essential for transformation, angiogenesis, invasion
      and metastasis. As a cancer progression model, we used NIH3T3 cells to explore
      the mechanism of Ras-induced tumorigenesis. Ras family mutants H-RasV12 and
      Rit79L strongly induced foci formation, while Rho family mutants RhoA-QL, Rac1-QL
      and Cdc42-QL were less effective. A comparison of downstream transcriptional
      targets of Ras and Rho family members using a 26 383 element cDNA microarray
      revealed that the osteopontin (OPN) gene exhibited the best correlation between
      magnitude of gene expression change and level of foci formation (r=0.96,
      P<0.001). In association with H-RasV12- and Rit79L-mediated transformation, foci
      secreted OPN protein and upregulated the OPN receptor CD44, suggesting the novel
      initiation of an aberrant OPN-CD44-Rac autocrine pathway. In support of this were
      the following observations. First, RGD-deficient OPN protein-binding activity was
      present in H-RasV12-transformed cells but not in control cells, and binding
      activity was inhibited by the CD44 blocking antibody. Second, foci formation,
      cell invasion and Rac activity were induced by H-RasV12 and inhibited by the CD44
      blocking antibody. Third, foci formation by H-RasV12 was substantially reduced by
      a short interfering RNA (siRNA) specifically targeting OPN expression for
      knockdown. Fourth, H-RasV12-mediated transformation was not blocked by the GRGDS
      peptide, suggesting that OPN effects were not mediated by the integrins. Lastly,
      OPN knockdown affected the downstream expression of 160 '2nd tier' genes, and at
      least a subset of these genes appears to be involved in transformation. Indeed,
      four genes were selected for knockdown, each resulting in a disruption of foci
      formation and/or invasion. These results underscore the role of aberrant
      autocrine signaling and transcriptional networking during tumorigenesis.

PMID- 15516974
TI  - Lyn deficiency reduces GATA-1, EKLF and STAT5, and induces extramedullary stress
      erythropoiesis.
AB  - In vitro studies have implicated the Lyn tyrosine kinase in erythropoietin
      signaling. In this study, we show that J2E erythroid cells lacking Lyn have
      impaired signaling and reduced levels of transcription factors STAT5a, EKLF and
      GATA-1. Since mice lacking STAT5, EKLF or GATA-1 have red cell abnormalities,
      this study also examined the erythroid compartment of Lyn(-/-) mice.
      Significantly, STAT5, EKLF and GATA-1 levels were appreciably lower in Lyn(-/-)
      erythroblasts, and the phenotype of Lyn(-/-) animals was remarkably similar to
      GATA-1(low) animals. Although young adult Lyn-deficient mice had normal
      hematocrits, older mice developed anemia. Grossly enlarged erythroblasts and
      florid erythrophagocytosis were detected in the bone marrow of mice lacking Lyn.
      Markedly elevated erythroid progenitors and precursor levels were observed in the
      spleens, but not bone marrow, of Lyn(-/-) animals indicating that extramedullary
      erythropoiesis was occurring. These data indicate that Lyn(-/-) mice display
      extramedullary stress erythropoiesis to compensate for intrinsic and extrinsic
      erythroid defects.

PMID- 15516975
TI  - Dissection of transcriptional programmes in response to serum and c-Myc in a
      human B-cell line.
AB  - Proliferation of higher eukaryotic cells is triggered by the proto-oncogene c-myc
      (myc), which is induced downstream of a large number of growth factor receptors.
      Myc, a basic helix-loop-helix leucine zipper transcription factor, transmits
      growth signals by up- and downregulation of target genes. The importance of Myc
      in growth control is well established. However, the number of growth control
      genes requiring Myc as an essential factor for regulation after mitogenic
      stimulation of cells is not yet clear. Here, we have studied the transcriptional
      programme of a human B-cell line, P493-6, in response to Myc and serum. P493-6
      cells do not express the endogenous myc, nor is it induced by serum stimulation.
      Proliferation of the cells is dependent upon both the expression of a
      tetracycline-regulated myc gene and serum stimulation. Using DNA microarrays,
      expression profiling was performed following stimulation of cells with serum,
      with Myc, or with both. We observed serum regulation of >1000 genes. A number of
      these genes were synergistically or antagonistically regulated by Myc. Moreover,
      we identified >300 Myc-regulated genes that were almost unresponsive to serum.
      Gene ontology analysis revealed that a high proportion of Myc target genes are
      involved in ribosome biogenesis and tRNA metabolism. The data support our current
      notion that Myc is essential for the regulation of a large number of growth
      related genes in B cells, and cannot be replaced by other serum-induced factors.

PMID- 15516976
TI  - Predisposition to mouse thymic lymphomas in response to ionizing radiation
      depends on variant alleles encoding metal-responsive transcription factor-1 (Mtf
      1).
AB  - Genetic predisposition to cancers is significant to public health because a high
      proportion of cancers probably arise in a susceptible human subpopulation. Using
      a mouse model of gamma-ray-induced thymic lymphomas, we performed linkage
      analysis and haplotype mapping that suggested Mtf-1, metal-responsive
      transcription factor-1 (Mtf-1), as a candidate lymphoma susceptibility gene.
      Sequence analysis revealed a polymorphism of Mtf-1 that alters the corresponding
      amino acid at position 424 in the proline-rich domain from a serine in
      susceptibility strains to proline in resistant strains. The transcriptional
      activity of Mtf-1 encoding serine and proline was compared by transfecting the
      DNA to Mtf-1-null cells, and the change to proline conferred a higher metal
      responsiveness in transfections. Furthermore, the resistant congenic strains
      possessing the Mtf-1 allele of proline type exhibited higher radiation
      inducibility of target genes than susceptible background strains having the Mtf-1
      allele of serine type. Since products of the targets such as metallothionein are
      able to suppress cellular stresses generated by irradiation, these results
      suggest that highly inducible strains having Mtf-1 of proline type are refractory
      to radiation effects and hence are resistant to lymphoma development.

PMID- 15516977
TI  - Rac1b, a tumor associated, constitutively active Rac1 splice variant, promotes
      cellular transformation.
AB  - A novel splice variant of Rac1, designated Rac1b, is expressed in human breast
      and colon carcinoma cells. Rac1b contains an additional 19 amino-acid insert
      immediately behind the switch II domain, a region important for Rac1 interaction
      with regulators and effectors. Recent studies showed that Rac1b exhibited the
      biochemical properties of a constitutively activated GTPase, yet it showed
      impaired interaction with downstream effectors, suggesting that Rac1b may be
      defective in biological activity. Whether Rac1b is a biologically active protein
      was not addressed. Therefore, we evaluated the biochemical, signaling and growth
      promoting properties of authentic Rac1b. Similar to previous observations, we
      found that Rac1b showed enhanced intrinsic guanine nucleotide exchange activity,
      impaired intrinsic GTPase activity, and failed to interact with RhoGDI.
      Surprisingly, we found that Rac1b, like the constitutively-activated and
      transforming Rac1(Q61L) mutant, promoted growth transformation of NIH3T3 cells.
      Rac1b-expressing cells also showed a loss of density-dependent and anchorage
      dependent growth. Surprisingly, unlike activated Rac1(61L), Rac1b did not show
      enhanced activation of the nuclear factor kappaB (NF-kappaB) transcription factor
      or stimulate cyclin D1 expression, the signaling activities that best correlate
      with Rac1 transforming activity. However, Rac1b did promote activation of the AKT
      serine/threonine kinase. Therefore, we suggest that Rac1b selectively activates a
      subset of Rac1 downstream signaling pathways to facilitate cellular
      transformation.

PMID- 15516978
TI  - Malignant mesothelioma as both a challenge and an opportunity.
AB  - The International Mesothelioma Interest Group sponsored its 7th international
      meeting in Brescia, Italy from June 24-26, 2004. The meeting, entitled 'How
      advanced technology and new drugs are changing the perspectives of patients with
      malignant mesothelioma', was organized by Luciano Mutti (Vercelli, Italy) and GF
      Tassi (Brescia, Italy) and was attended by 350 participants. The general tone of
      the meeting was that real progress is now coming in the understanding of
      mesothelioma biology, progress that may soon translate into improved treatment
      options. The investigators and clinicians agreed on the importance of referring
      patients with mesothelioma to centers with expertise where patients can receive
      the best available treatments and can be offered entry into clinical trials of
      new and promising agents.

PMID- 15516979
TI  - The serine-threonine kinase MNK1 is post-translationally stabilized by PML
      RARalpha and regulates differentiation of hematopoietic cells.
AB  - Microarray analyses were performed to identify target genes that are shared by
      the acute myeloid leukemia (AML) translocation products PML-RARalpha, PLZF
      RARalpha and AML1-ETO in inducibly transfected U937 cell lines. The cytoplasmic
      serine and threonine kinase MNK1 was identified as one of the target genes. At
      the protein level, MNK1 was significantly induced by each of the three fusion
      proteins. Protein half-life analyses showed that PML-RARalpha enhanced MNK1
      protein stability in U937 cells and ATRA exposure decreased MNK1 half-life in NB4
      cells. EIF4E, the main MNK1 substrate, plays a role in the pathogenesis of a
      variety of cancers. Upon MNK1 overexpression, eIF4E phosphorylation increased as
      a sign of functional activation. Interestingly, MNK1 protein expression decreased
      during myeloid differentiation. Inhibition of MNK1 activity by a specific
      inhibitor (CGP57380) enhanced differentiation of HL60 and 32D cells, further
      suggesting a role for MNK1 in the myeloid differentiation. In addition, kinase
      dead mutants of MNK1 significantly impaired proliferation of 32D cells.
      Immunohistochemistry of primary AML bone marrow biopsies showed strong
      cytoplasmic MNK1 expression in 25 of 99 AML specimens (25%). MNK1 expression was
      associated with high levels of c-myc expression. Taken together, we identified
      MNK1 as a target gene of several leukemogenic fusion proteins in AML. MNK1 plays
      a role in myeloid differentiation. These data suggest a role for MNK1 in the AML
      fusion protein-associated differentiation block.

PMID- 15516980
TI  - The Phox2B homeobox gene is mutated in sporadic neuroblastomas.
AB  - Neuroblastomas are embryonal tumours of the sympatho-adrenal lineage with a
      clinical course ranging from spontaneous regression to fatal progression. The
      Phox2B homeobox transcription factor functions in the differentiation of the
      sympatho-adrenal lineage. Targets of Phox2B are, for example, genes of the
      (nor)adrenalin synthesis route, like Dopamine Beta Hydroxylase (DBH). Congenital
      Central Hypoventilation Syndrome was recently found to result from Phox2B
      mutations and two such patients in addition developed neuroblastoma. A germline
      mutation in Phox2B was identified in a family with hereditary neuroblastoma.
      Here, we report the first analysis of Phox2B in a series of 237 sporadic
      neuroblastomas and 22 cell lines. Six frameshift mutations were found in exons 2
      and 3; including one in cell line SK-N-SH. Two patients showed de novo
      constitutional mutations. One of them was diagnosed with Haddad syndrome. All
      analysed cases expressed the mutated and wild-type Phox2B alleles. Ectopic
      expression of TrkA, the Nerve Growth Factor receptor, strongly downregulated
      Phox2B and DBH expression in cell line SH-SY5Y. However, TrkA and Phox2B showed a
      positive correlation in a panel of 66 neuroblastoma tumours. Although Phox2B
      mutations are infrequent (2.3%), they implicate a role for the Phox2B pathway in
      oncogenesis.

PMID- 15516981
TI  - Inhibition of human bladder tumour cell growth by fibroblast growth factor
      receptor 2b is independent of its kinase activity. Involvement of the carboxy
      terminal region of the receptor.
AB  - The b isoform of fibroblast growth factor receptor 2, FGFR2b/FGFR2-IIIb/Ksam
      IIC1/KGFR, a tyrosine kinase receptor, is expressed in a wide variety of
      epithelia and is downregulated in several human carcinomas including prostate,
      salivary and urothelial cell carcinomas. FGFR2b has been shown to inhibit growth
      in tumour cell lines derived from these carcinomas. Here, we investigated the
      molecular mechanisms underlying the inhibition of human urothelial carcinoma cell
      growth following FGFR2b expression. Using a nylon DNA array, we analysed the gene
      expression profile of the T24 bladder tumour cell line, transfected or not with a
      construct encoding FGFR2b. The expression of FGFR2b in T24 cells decreased
      insulin-like growth factor (IGF)-II mRNA levels. This decrease was correlated
      with a decrease in IGF-II secretion and may have been responsible for the
      observed inhibition of cell growth because the addition of exogenous IGF-II
      restored growth rates to normal levels. Using SU5402, an inhibitor of FGFR
      tyrosine kinase activity, and a kinase dead mutant of the receptor, FGFR2b
      Y659F/Y660F, we also demonstrated that the growth inhibition and decrease in IGF
      II secretion induced by FGFR2b did not require tyrosine kinase activity. Finally,
      we demonstrated the involvement of the distal carboxy-terminal domain of the
      receptor in decreasing IGF-II expression and inhibiting T24 cell growth, as Ksam
      IIC3, a variant of FGFR2b carrying a short carboxy-terminus, neither
      downregulated IGF-II nor inhibited cell proliferation. Our data suggest that
      FGFR2b inhibits the growth of bladder carcinoma cells by reducing IGF-II levels
      via its carboxy-terminal domain, independent of its tyrosine kinase activity.

PMID- 15516982
TI  - Regulation of c-Met-dependent gene expression by PTEN.
AB  - Receptor tyrosine kinases (RTK) and the tumor suppressor PTEN co-regulate
      oncogenic cell signaling pathways. How these interactions influence gene
      transcription is inadequately understood. We used expression microarrays to
      investigate the effects of PTEN on gene expression changes caused by activating c
      Met in human glioblastoma cells. c-Met activation by scatter factor/hepatocyte
      growth factor (SF/HGF) altered the expression of 27-fold more genes in PTEN-null
      U-373MG cells than in PTEN homozygous primary normal human astrocytes (523 vs 19
      genes). Restoring wt-PTEN in U-373MG cells dramatically altered patterns of c-Met
      regulated gene expression. This effect was varied depending on the specific gene
      in question. PTEN reduced the number of c-Met regulated transcripts from 931 to
      502, decreased the relative number of genes upregulated by c-Met from 46 to 25%,
      and increased the relative number of downregulated genes from 54 to 75%. PTEN and
      c-Met co-regulated many genes involved in cell growth regulation such as
      oncogenes, growth factors, transcription factors, and constituents of the
      ubiquitin pathway. c-Met activation in PTEN-null (but not PTEN reconstituted)
      cells led to upregulation of the EGFR agonist TGFalpha and subsequently to EGFR
      activation. Using PTEN mutants, we found that PTEN's transcriptional effects were
      either lipid-phosphatase dependent, protein-phosphatase dependent, or phosphatase
      independent. These results show that PTEN has critical and mechanistically
      complex effects on RTK-regulated gene transcription. These findings expand our
      understanding of tumor promoter/suppressor inter-relationships and downstream
      transcriptional effects of PTEN loss and c-Met overexpression in malignant
      gliomas.

PMID- 15516983
TI  - Dickkopf-3/REIC functions as a suppressor gene of tumor growth.
AB  - To identify putative tumor suppressor genes in hepatocarcinogenesis, we combined
      the representational difference analysis and reverse northern blot identifying
      downregulated genes in human hepatoma tissues. One of them was Dkk-3/REIC. Dkk
      3/REIC was downregulated in 11 out of the 20 human hepatoma tissues as compared
      to their counterparts of noncancerous liver tissues by northern blot analysis. It
      was also downregulated in 29 out of 48 human cancer samples including the kidney,
      urinary bladder, prostate, pancreas and lung cancers. Its gene product, Dkk
      3/REIC, was found to be N-glycosylated and have two isoforms, the 55 kDa in the
      cytosol and 50 kDa secreted in the medium. Ectopic expression of Dkk-3/REIC in
      HeLa, Hep3B and Huh 7 cells led to suppression of cell growth, which was
      primarily attributable to induction of cell apoptosis. The suppression phenomenon
      was found to be cell-type related (most prominent in HeLa and least in Hep3B
      cells) and cell-density dependent (attenuated as the cell density increased).
      Transduction of Dkk-3/REIC into HeLa and Hep3B cells caused suppression on colony
      formation in vitro and reduced tumor growth rate in inoculated athymic nude mice.
      In conclusion, these data indicate that Dkk-3/REIC functions as a suppressor for
      human tumor growth.

PMID- 15516984
TI  - LRP6 expression promotes cancer cell proliferation and tumorigenesis by altering
      beta-catenin subcellular distribution.
AB  - The Wnt signaling pathway plays key roles in both embryogenesis and
      tumorigenesis. The low-density lipoprotein (LDL) receptor-related protein-6
      (LRP6), a novel member of the expanding LDL receptor family, functions as an
      indispensable co-receptor for the Wnt signaling pathway. Although the role of
      LRP6 in embryonic development is now well established, its role in tumorigenesis
      is unclear. We report that LRP6 is readily expressed at the transcript level in
      several human cancer cell lines and human malignant tissues. Furthermore, using a
      retroviral gene transfer system, we find that stable expression of LRP6 in human
      fibrosarcoma HT1080 cells alters subcellular beta-catenin distribution such that
      the cytosolic beta-catenin level is significantly increased. This is accompanied
      by a significant increase in Wnt/beta-catenin signaling and cell proliferation.
      Finally, we demonstrate that LRP6 expression promotes tumorigenesis in vivo.
      These results thus indicate that LRP6 may function as a potential oncogenic
      protein by modulating Wnt/beta-catenin signaling.

PMID- 15516985
TI  - ERK couples chronic survival of NK cells to constitutively activated Ras in
      lymphoproliferative disease of granular lymphocytes (LDGL).
AB  - Chronic NK lymphoproliferative disease of large granular lymphocytes (LDGL) is
      characterized by the expansion of activated CD3-, CD16+ or CD56+ lymphocytes. The
      mechanism of survival of NK cells from LDGL patients is unknown but may be
      related to antigenic stimulation. There is currently no standard effective
      therapy for LDGL, and the disease is characteristically resistant to standard
      forms of chemotherapy. We found evidence of constitutive activation of
      extracellular-regulated kinase (ERK) in NK cells from 13/13 patients with NK-LDGL
      (one patient with aggressive and 12 patients with chronic disease). Ablation of
      ERK activity by inhibitors or a dominant-negative form of MEK, the upstream
      activator of ERK, reduced the survival of patient NK cells. Ras was also
      constitutively active in patient NK cells, and exposure of cells to the Ras
      inhibitor FTI2153 or to dominant-negative-Ras resulted not only in ERK inhibition
      but also in enhanced apoptosis in both the presence and absence of anti-Fas.
      Therefore, we conclude that a constitutively active Ras/MEK/ERK pathway
      contributes to the accumulation of NK cells in patients with NK-LDGL. These
      findings suggest that strategies to inhibit this signaling pathway may be useful
      for the treatment of the NK type of LDGL.

PMID- 15516986
TI  - Retinoic acid mediates degradation of IRS-1 by the ubiquitin-proteasome pathway,
      via a PKC-dependant mechanism.
AB  - Insulin receptor substrate-1 (IRS-1) mediates signaling from the insulin-like
      growth factor type-I receptor. We found that all-trans retinoic acid (RA)
      decreases IRS-1 protein levels in MCF-7, T47-D, and ZR75.1 breast cancer cells,
      which are growth arrested by RA, but not in the RA-resistant MDA-MB-231 and MDA
      MB-468 cells. Based on prior reports of ubiquitin-mediated degradation of IRS-1,
      we investigated the ubiquitination of IRS-1 in RA-treated breast cancer cells.
      Two proteasome inhibitors, MG-132 and lactacystin, blocked the RA-mediated
      degradation of IRS-1, and RA increased ubiquitination of IRS-1 in the RA
      sensitive breast cancer cells. In addition, we found that RA increases serine
      phosphorylation of IRS-1. To elucidate the signaling pathway responsible for this
      phosphorylation event, pharmacologic inhibitors were used. Two PKC inhibitors,
      but not a MAPK inhibitor, blocked the RA-induced degradation and serine
      phosphorylation of IRS-1. We demonstrate that RA activates PKC-delta in the
      sensitive, but not in the resistant cells, with a time course that is consistent
      with the RA-induced decrease of IRS-1. We also show that: (1) RA-activated PKC
      delta phosphorylates IRS-1 in vitro, (2) PKC-delta and IRS-1 interact in RA
      treated cells, and (3) mutation of three PKC-delta serine sites in IRS-1 to
      alanines results in no RA-induced in vitro phosphorylation of IRS-1. Together,
      these results indicate that RA regulates IRS-1 levels by the ubiquitin-proteasome
      pathway, involving a PKC-sensitive mechanism.

PMID- 15516987
TI  - Tissue inhibitor of matrix metalloproteinase-1 overexpression in M1 myeloblasts
      impairs IL-6-induced differentiation.
AB  - The balance between matrix metalloproteinase (MMP) and tissue inhibitor of matrix
      metalloproteinase (TIMP) is important for extracellular matrix interactions of
      hematopoietic cells. MMP-independent growth modulating activity for TIMP-1 on B
      lymphocytes and erythroid progenitors has also been described, but a role for
      TIMP-1 in myelomonocytic differentiation has not been previously reported. In
      this study, we demonstrate that TIMP-1 overexpression impairs differentiation of
      the myeloblastic M1 cell line following interleukin (IL)-6 stimulation. We
      generated retroviral vectors coexpressing human TIMP-1 and the green fluorescent
      protein (GFP) and stably transduced murine M1 myeloid cells. TIMP-1 expressing
      cells showed a large reduction in IL-6-induced macrophage differentiation in
      vitro that was reversible with a specific monoclonal antibody. The
      differentiation delay in M1/TIMP-1 cells was also specifically reversible by
      pharmacologic phosphatidylinositol-3 kinase (PI3-K) inhibition. Additionally,
      overexpression of a TIMP-1/GFP fusion protein also impaired M1 differentiation
      and this protein was localized to the cell surface, consistent with an autocrine
      receptor-mediated mechanism. Surprisingly, TIMP-1 transduced cells had a
      selective advantage for growth in IL-6, indicating that functional effects on
      growth and differentiation of M1 cells were primarily through an autocrine
      mechanism. Intrinsic TIMP-1 expression in myeloid leukemia cells might thus
      impact upon survival or differentiation.

PMID- 15516988
TI  - The ATM gene is a target for epigenetic silencing in locally advanced breast
      cancer.
AB  - Several epidemiological studies on ataxia-telangiectasia families indicate that
      obligate ATM heterozygotes display an elevated risk for developing breast cancer.
      However, a molecular basis for a potential link between diminished ATM function
      and sporadic breast malignancy remains elusive. Here, we show that 78% (18 out of
      a panel of 23) of surgically removed breast tumors (stage II or greater)
      displayed aberrant methylation of the ATM proximal promoter region as judged by
      methylation-specific PCR. Aberrant methylation of the ATM promoter was
      independently confirmed in several tumors by bisulfite sequencing. Moreover,
      bisulfite sequencing indicated that this region of the genome is subject to dense
      methylation. Further, we found a highly significant correlation (P = 0.0006)
      between reduced ATM mRNA abundance, as measured by real-time RT-PCR, and aberrant
      methylation of the ATM gene promoter. These findings indicate that epigenetic
      silencing of ATM expression occurs in locally advanced breast tumors, and
      establish a link at the molecular level between reduced ATM function and sporadic
      breast malignancy.

PMID- 15516989
TI  - Adenine deoxynucleotides fludarabine and cladribine induce apoptosis in a
      CD95/Fas receptor, FADD and caspase-8-independent manner by activation of the
      mitochondrial cell death pathway.
AB  - The adenine deoxynucleosides cladribine (2CdA) and fludarabine (FAraA) are DNA
      damaging agents that interfere with DNA repair and induce apoptosis in
      nonproliferating lymphoid cells. Although both drugs are clinically used for the
      treatment of indolent lymphoproliferative diseases, the pathways of apoptosis
      induction remain largely unknown. In the present work, we demonstrate that both
      drugs induce apoptosis independently of death receptor signaling but activate the
      mitochondrial cell death pathway. To dissect the signaling pathways, we employed
      Jurkat cells either deficient for FADD or caspase-8 or overexpressing Bcl-2. In
      Bcl-2 overexpressing cells, apoptosis and cytochrome c release were blocked
      whereas processing of caspase-9, -3 and -8 was partially inhibited. In contrast,
      neither the deficiency of FADD or caspase-8 nor the interference with death
      receptor signaling by neutralizing anti-CD95/Fas antibodies affected cell death.
      Inhibitor experiments revealed that caspase-8 is processed by caspase-3-like
      caspases. Moreover, cytochrome c release and processing of caspase-9 and -3
      occurred to an equal extent in wild-type FADD -/- and caspase-8 -/- Jurkat cells.
      Likewise, apoptosis induction by cladribine or fludarabine was not hampered upon
      inhibition of caspase-8 in MOLT-3 and MOLT-4 cells or overexpression of a
      dominant-negative FADD mutant in BJAB cells. Thus, we conclude that apoptosis
      induced by nucleoside analogues is independent from death receptor signaling as
      well as from a proposed direct effect on APAF-1, but rather follows the
      mitochondrial signaling pathway of cytochrome c release and subsequent processing
      of caspase-9 and -3.

PMID- 15516990
TI  - A prize for protein degradation.

PMID- 15516991
TI  - Actin's many actions start at the genes.

PMID- 15516992
TI  - MRL proteins: leading Ena/VASP to Ras GTPases.

PMID- 15516994
TI  - Cellular sources of new pancreatic beta cells and therapeutic implications for
      regenerative medicine.
AB  - Replacing missing insulin-producing beta cells to treat diabetes is a major
      challenge for regenerative medicine. A better understanding of beta-cell
      embryogenesis and regeneration in adult life is needed to devise means to derive
      these specialized cells in sufficiently large numbers from stem or precursor
      cells. It is also critical to ensure that any surrogate or regenerated beta cells
      have perfectly regulated insulin production, which is essential for physiological
      glucose homeostasis.

PMID- 15516995
TI  - Subversion of phosphoinositide metabolism by intracellular bacterial pathogens.
AB  - Phosphoinositides are short-lived lipids, whose production at specific membrane
      locations in the cell enables the tightly controlled recruitment or activation of
      diverse cellular effectors involved in processes such as cell motility or
      phagocytosis. Bacterial pathogens have evolved molecular mechanisms to subvert
      phosphoinositide metabolism in host cells, promoting (or blocking) their
      internalization into target tissues, and/or modifying the maturation fate of
      their proliferating compartments within the intracellular environment.

PMID- 15516996
TI  - The many faces of filamin: a versatile molecular scaffold for cell motility and
      signalling.
AB  - Filamins were discovered as the first family of non-muscle actin-binding protein.
      They are lage cytoplasmic proteins that cross-link cortical actin into a dynamic
      three-dimensional structure. Filamins have also been reported to interact with a
      large number of cellular proteins of great functional diversity, suggesting that
      they are unusually versatile signalling scaffolds. More recently, genetic
      mutations in filamin A and B have been reported to cause a wide range of human
      diseases, suggesting that different diseases highlight distinct filamin
      interactions.

PMID- 15516997
TI  - Ion channels: function unravelled by dysfunction.
AB  - Ion channels allow the passage of specific ions and electrical charge. Plasma
      membrane channels are, for example, important for electrical excitability and
      transepithelial transport, whereas intracellular channels have roles in
      acidifying endosomes or in releasing Ca(2+) from stores. The function of several
      channels emerged from mutations in humans or mice. The resulting phenotypes
      include kidney stones resulting from impaired endocytosis, hypertension,
      defective insulin secretion, cardiac arrhythmias, neurological diseases like
      epilepsy or deafness and even 'developmental' defects such as osteopetrosis.

PMID- 15516998
TI  - RNA and microRNAs in fragile X mental retardation.
AB  - Fragile X syndrome is caused by the loss of an RNA-binding protein called FMRP
      (for fragile X mental retardation protein). FMRP seems to influence synaptic
      plasticity through its role in mRNA transport and translational regulation.
      Recent advances include the identification of mRNA ligands, FMRP-mediated mRNA
      transport and the neuronal consequence of FMRP deficiency. FMRP was also recently
      linked to the microRNA pathway. These advances provide mechanistic insight into
      this disorder, and into learning and memory in general.

PMID- 15516999
TI  - Cell biology of protein misfolding: the examples of Alzheimer's and Parkinson's
      diseases.
AB  - The salutary intersection of fundamental cell biology with the study of disease
      is well illustrated by the emerging elucidation of neurodegenerative disorders.
      Novel mechanisms in cell biology have been uncovered through disease-orientated
      research; for example, the discovery of presenilin as an intramembrane aspartyl
      protease that processes many diverse proteins within the lipid bilayer. A common
      theme has arisen in this field: normally-soluble proteins accumulate, misfold and
      oligomerize, inducing cytotoxic effects that are particularly devastating in the
      post-mitotic milieu of the neuron.

PMID- 15517000
TI  - A-type lamins: guardians of the soma?
AB  - The gene LMNA encodes the proteins lamins A and C and is implicated in nine
      different laminopathies - inherited diseases that are linked to premature ageing.
      Recent evidence has demonstrated that lamins A and C have essential functions in
      protecting cells from physical damage, as well as in maintaining the function of
      transcription factors required for the differentiation of adult stem cells. Thus,
      the degenerative nature of laminopathies is explained because these lamins are
      essential for maintenance of somatic tissues in adulthood.

PMID- 15517001
TI  - Unravelling the secrets of the crypts.

PMID- 15517002
TI  - A dermal niche for multipotent adult skin-derived precursor cells.
AB  - A fundamental question in stem cell research is whether cultured multipotent
      adult stem cells represent endogenous multipotent precursor cells. Here we
      address this question, focusing on SKPs, a cultured adult stem cell from the
      dermis that generates both neural and mesodermal progeny. We show that SKPs
      derive from endogenous adult dermal precursors that exhibit properties similar to
      embryonic neural-crest stem cells. We demonstrate that these endogenous SKPs can
      first be isolated from skin during embryogenesis and that they persist into
      adulthood, with a niche in the papillae of hair and whisker follicles.
      Furthermore, lineage analysis indicates that both hair and whisker follicle
      dermal papillae contain neural-crest-derived cells, and that SKPs from the
      whisker pad are of neural-crest origin. We propose that SKPs represent an
      endogenous embryonic precursor cell that arises in peripheral tissues such as
      skin during development and maintains multipotency into adulthood.

PMID- 15517003
TI  - Organization of a sterol-rich membrane domain by cdc15p during cytokinesis in
      fission yeast.
AB  - Many membrane processes occur in discrete membrane domains containing lipid
      rafts, but little is known about how these domains are organized and positioned.
      In the fission yeast Schizosaccharomyces pombe, a sterol-rich membrane domain
      forms at the cell-division site. Here, we show that formation of this membrane
      domain is independent of the contractile actin ring, septation, mid1p and the
      septins, and also requires cdc15p, an essential contractile ring protein that
      associates with lipid rafts. cdc15 mutants have membrane domains in the shape of
      spirals. Overexpression of cdc15p in interphase cells induces abnormal membrane
      domain formation in an actin-independent manner. We propose that cdc15p functions
      to organize lipid rafts at the cleavage site for cytokinesis.

PMID- 15517004
TI  - Just another cost increasing exercise (JACIE)?

PMID- 15517005
TI  - Implementation of the JACIE standards for a haematopoietic progenitor cell
      transplantation programme: a cost analysis.
AB  - The purpose of the present project was to analyse the costs incurred by the
      implementation of JACIE standards at a University Hospital with 1000 beds,
      performing some 40 autologous transplants per year. The cost analysis was
      performed on the basis of a prospective assessment of the time spent by all staff
      members involved with the implementation over a 14-month period of the quality
      management system (QMS) required by the JACIE standards. Two physicians worked on
      JACIE Section A (management=82 h), one physician and two nurses for section Ba
      (clinical unit adults=125.75 h), two physicians and three nurses for section Bp
      (clinical unit paediatrics=206 h), one physician, two nurses and one technician
      for section C (progenitor cell collection facility=105.75 h), and one physician
      and two technicians for section D (progenitor cell processing facility=426 h).
      The total time spent on the project amounted to 945.5 h with a total salary cost
      of ?[euro]150 000. We concluded that implementation of the JACIE standards was
      accomplished within a 14-month period with a financial impact of approximately
      ?[euro]150 000. The impact on quality parameters (eg clinical and laboratory end
      points, side effects) on HPC transplantation will be assessed in a second report
      after the first year of practical implementation.

PMID- 15517006
TI  - Haematopoietic stem cell transplantation (HSCT) in Europe 2002. Changes in
      indication and impact of team density. A report of the EBMT activity survey.
AB  - This 2002 European Group for Blood and Marrow Transplantation (EBMT) activity
      survey concentrates on current status, increase and decrease in haematopoietic
      stem cell transplantation (HSCT) activity in Europe and investigates the
      association of transplant rates with team density. In 2002, there were 20 207
      HSCT, 6915 allogeneic (34%), 13 292 autologous (66%) and 3947 additional re- or
      multiple transplants collected from 586 centres in 39 European countries. Main
      indications were leukaemias (6523 (32%; 76% allogeneic)); lymphomas (10 760 (53%;
      92% autologous)); solid tumours (1913 (9%; 92% autologous)) and nonmalignant
      disorders (874 (4%; 92% allogeneic)). Compared to 2001, there were increases
      (>10%) for AML, ALL 1st CR, CML not 1st cP, MDS, SAA and CLL in allogeneic HSCT
      and for MDS, Ewing's sarcoma, soft-tissue sarcoma and ovarian cancer in
      autologous HSCT. Decreases (>10%) were observed in autologous HSCT for acute
      leukaemias beyond 1st CR, CML cP, glioma, breast cancer and lung cancer.
      Correlation of transplant rates (number of transplants per 10 million
      inhabitants) with team density (number of transplant teams per 10 million
      inhabitants) suggests different diffusion patterns for autologous compared to
      allogeneic HSCT. These data describe current practice for blood and marrow
      transplantation in Europe and give some hints about mechanisms involved in HSCT
      rates.

PMID- 15517007
TI  - Consensus statement concerning cardiotoxicity occurring during haematopoietic
      stem cell transplantation in the treatment of autoimmune diseases, with special
      reference to systemic sclerosis and multiple sclerosis.
AB  - Autologous haematopoietic stem cell transplantation is now a feasible and
      effective treatment for selected patients with severe autoimmune diseases.
      Worldwide, over 650 patients have been transplanted in the context of phase I and
      II clinical trials. The results are encouraging enough to begin randomised phase
      III trials. However, as predicted, significant transplant-related morbidity and
      mortality have been observed. This is primarily due to complications related to
      either the stage of the disease at transplant or due to infections. The number of
      deaths related to cardiac toxicity is low. However, caution is required when
      cyclophosphamide or anthracyclines such as mitoxantrone are used in patients with
      a possible underlying heart damage, for example, systemic sclerosis patients. In
      November 2002, a meeting was held in Florence, bringing together a number of
      experts in various fields, including rheumatology, cardiology, neurology,
      pharmacology and transplantation medicine. The object of the meeting was to
      analyse existing data, both published or available, in the European Group for
      Blood and Marrow Transplantation autoimmune disease database, and to propose a
      safe approach to such patients. A full cardiological assessment before and during
      the transplant emerged as the major recommendation.

PMID- 15517008
TI  - Autologous stem cell transplantation followed by consolidation chemotherapy for
      relapsed or refractory Hodgkin's lymphoma.
AB  - Relapse remains a major cause of treatment failure after autotransplantation
      (auto-PBSCT) for Hodgkin's disease (HD). The administration of non-crossresistant
      therapies during the post-transplant period may delay or prevent relapse. We
      prospectively studied the role of consolidation chemotherapy (CC) after auto
      PBSCT in 37 patients with relapsed or refractory HD. Patients received high-dose
      gemcitabine-BCNU-melphalan and auto-PBSCT followed by involved-field radiation
      and up to four cycles of the DCEP-G regimen, which consisted of dexamethasone,
      cyclophosphamide, etoposide, cisplatin, gemcitabine given at 3 and 9 months post
      transplant alternating with a second regimen (DPP) of dexamethasone, cisplatin,
      paclitaxel at 6 and 12 months post transplant. The probabilities of event-free
      survival (EFS) and overall survival (OS) at 2.5 years were 59% (95% CI=42-76%)
      and 86% (95% CI=71-99%), respectively. In all, 17 patients received 54 courses of
      CC and 15 were surviving event free (2.5 years, EFS=87%). There were no treatment
      related deaths during or after the CC phase. Post-transplant CC is feasible and
      well tolerated. The impact of this approach on EFS should be evaluated in a
      larger, randomized study.

PMID- 15517009
TI  - Candidaemia in allogeneic stem cell transplant recipients: low risk without
      fluconazole prophylaxis.
AB  - Invasive fungal infections (IFI) are common in allogeneic SCT recipients. We have
      reviewed our experience of IFI with special reference to candidaemia in 685 adult
      patients transplanted in 1983-2002. The donor was a matched sibling in 505
      patients and an unrelated donor in 180 patients. A BM graft was used in 561
      patients and a PB graft in 124 patients. Fluconazole prophylaxis was not used
      during the study period. Definite or probable IFI was observed in 60 patients
      (8.7%) with a dominance of Aspergillus infections (46 patients, incidence 6.7%).
      Candidaemia was found only in nine patients (1.3%). The causative agents were
      Candida albicans (n=8), C. krusei (n=2), and C. glabrata (n=1); in two patients,
      two causative agents were found. The median time to the diagnosis of candidaemia
      was 53 days (range 6-249 days) post transplant. Seven patients were neutropaenic
      at diagnosis, and four patients had experienced acute GVHD. All patients received
      antifungal therapy, but only one patient was cured. According to this study,
      candidaemia was a rare event in allogeneic SCT recipients. Thus, systematic
      prophylaxis against Candida infections might not be indicated. The prognosis of
      established infections is still poor due to comorbid conditions, notably GVHD.

PMID- 15517010
TI  - Nonmyeloablative stem cell transplantation following a cytoreductive autograft in
      patients with non-Hodgkin's lymphoma who relapse after autologous
      transplantation.

PMID- 15517012
TI  - RNA interference-based functional genomics in cancer research--an introduction.

PMID- 15517013
TI  - RNAi in a postmodern, postgenomic era.
AB  - As dsRNA-mediated interference (RNAi) libraries become more widely available,
      genome-wide loss of function experiments in cell culture are likely to become a
      routine laboratory tool. RNAi screens can then be conducted to test gene
      functions in different assays in a variety of cell types and across species. In
      comparing these large phenotypic data sets, researchers will gain a new
      perspective, enabling them to see each gene as part of a fluid network that is
      remodelled in response to changes in environmental and developmental context, and
      with the passage of evolutionary time.

PMID- 15517015
TI  - Towards full employment: using RNAi to find roles for the redundant.
AB  - Cancer is a genetic disease that ultimately results from the failure of cells to
      respond correctly to diverse signals. Signal transduction and signal integration
      are highly complex, requiring the combinatorial interaction of multiple genes.
      Classical genetics in model organisms including Caenorhabditis elegans has been
      of immense use in identifying nonredundant components of conserved signalling
      pathways. However, it is likely that there is much functional redundancy in the
      informational processing machinery of metazoan cells; we therefore need to
      develop methods for uncovering such redundant functions in model organisms if we
      are to use them to understand complex gene interactions and oncogene cooperation.
      RNAi may provide a powerful tool to probe redundancy in informational networks.
      In this review, I set out some of the progress made so far by classical genetics
      in understanding redundancy in gene networks, and outline how RNAi may allow us
      to approach this problem more systematically in C. elegans. In particular, I
      discuss the use of genome-wide RNAi screens in C. elegans to identify synthetic
      lethal interactions and compare this with synthetic lethal interaction analysis
      in Saccharomyces cerevisiae.

PMID- 15517014
TI  - Genome-wide RNAi screens in Caenorhabditis elegans: impact on cancer research.
AB  - Genes linked to human cancers often function in evolutionary conserved pathways,
      and research in C. elegans has been instrumental in dissecting some of the
      pathways affected, such as apoptosis and Ras signalling. The advent of RNA
      interference (RNAi) technology has allowed high-throughput loss-of-function
      analyses of C. elegans gene functions. Here we review some of the most recent
      genome-wide RNAi screens that have been conducted and discuss their impact on
      cancer research and possibilities for future screens. We also show that genes
      causally implicated in human cancers are significantly more likely to have a C.
      elegans homologue than average, validating the use of C. elegans as a cancer gene
      discovery platform. We foresee that genome-wide RNAi screens in C. elegans will
      continue to be productive in identifying new cancer gene candidates and will
      provide further insights into cancer gene functions.

PMID- 15517016
TI  - High-throughput gene silencing using cell arrays.
AB  - A recently established transfected cell array (TCA) technology has opened new
      experimental dimensions in the field of functional genomics. Cell arrays allow
      for transfection of several thousands different DNA molecules in microarray
      format. The effects of overexpression of hundreds of proteins on cellular
      physiology can be observed in a single experiment. The TCA technique has also
      found its application in RNA interference (RNAi) research. Small interfering RNAs
      (siRNA) as well as plasmid expressing short hairpin RNAs can be transferred into
      the cells through the process of reverse transfection. The silencing of numerous
      genes in spatially separated manner can be thus monitored. This review will
      provide an overview on current concepts concerning combination of cell array and
      RNAi for high-throughput loss-of-function studies.

PMID- 15517017
TI  - Using RNAi to catch Drosophila genes in a web of interactions: insights into
      cancer research.
AB  - The completion of whole-genome sequencing of various model organisms and the
      recent explosion of new technologies in the field of Functional Genomics and
      Proteomics is poised to revolutionize the way scientists identify and
      characterize gene function. One of the most significant advances in recent years
      has been the application of RNA interference (RNAi) as a means of assaying gene
      function. In the post-genomic era, advances in the field of cancer biology will
      rely upon the rapid identification and characterization of genes that regulate
      cell growth, proliferation, and apoptosis. Significant efforts are being directed
      towards cancer therapy and devising efficient means of selectively delivering
      drugs to cancerous cells. In this review, we discuss the promise of integrating
      genome-wide RNAi screens with proteomic approaches and small-molecule chemical
      genetic screens, towards improving our ability to understand and treat cancer.

PMID- 15517018
TI  - Genomic instability and cancer: scanning the Caenorhabditis elegans genome for
      tumor suppressors.
AB  - Maintaining the stability of the genome is critical to normal cell growth and
      development. The early notion that cancer is the result of mutations in genes
      controlling cellular growth implied that gene or genome integrity is vital to the
      prevention of oncogenesis, and many genes and pathways that prevent genomic
      deterioration have been identified over the past decades. Recent progress in
      reverse genetic approaches, principally RNA interference, now allows the
      systematic analysis of gene function on a genomic scale in an animal system.
      Here, we discuss genomic approaches in the model organism Caenorhabditis elegans,
      aimed to identify genes and genetic networks that contribute to genome stability
      and are thus potentially involved in human carcinogenesis.

PMID- 15517019
TI  - Use of RNA interference libraries to investigate oncogenic signalling in
      mammalian cells.
AB  - Over the past decade, 'RNA interference' has emerged as a natural mechanism of
      silencing of gene expression. This ancient cellular antiviral response can be
      manipulated to provide an effective research tool to knock down the level of
      expression of selected target genes, providing a very powerful new method for the
      analysis of cell signalling pathways. Systematic silencing of genes on a genome
      wide scale using large rationally designed libraries targeting many thousands of
      genes provides a novel functional genomics approach to the investigation of many
      aspects of mammalian cell behaviour, including oncogenic transformation. Here,
      the different approaches taken to use RNA interference libraries to study the
      cancer phenotype will be considered, including both selective and high throughput
      screens and the use of both vector-based and synthetic oligonucleotide-based
      methods for inducing RNA interference. The advantages and drawbacks of the
      competing methodologies will be discussed. RNA interference library technology
      holds great promise for enabling somatic cell genetics in tissue culture systems.
      Whether it can provide significant new insights into cancer will be its greatest
      challenge.

PMID- 15517020
TI  - Oncology studies using siRNA libraries: the dawn of RNAi-based genomics.
AB  - High-throughput, human cell-based applications of RNA-mediated interference
      (RNAi) have emerged in recent years as perhaps the most powerful of a 'second
      wave' of functional genomics technologies. The available reagents and
      methodologies for RNAi screening studies now enable a wide range of different
      scopes and scales of investigation, from single-parameter assays applied to
      focused subsets of genes, to comprehensive genome-wide surveys based on rich,
      multiparameter readouts. As such, RNAi-based screens are offering important new
      avenues for the discovery and validation of novel therapeutic targets for several
      disease areas, including oncology. By enabling a 'clean' determination of gene
      function, that is the creation of direct causal links between gene and phenotype
      in human cells, RNAi investigations promise levels of pathophysiological
      relevance, efficiency, and range of applicability never before possible on this
      scale. The field of oncology, with its many assays using readily transfectable
      cell lines, has offered particularly fertile ground for showcasing the potential
      of RNAi-based genomics. However, like any other technology before it, RNAi is not
      without its own challenges, limitations, and caveats. Many of these issues stem
      directly from the choice of silencing reagent to be used in such studies, and the
      design of the overall screening strategy. Here, we discuss the basic design
      issues, potential advantages, and technical challenges of large-scale RNAi
      screens based on the use of chemically synthesized siRNA libraries.

PMID- 15517021
TI  - RNAi and HTS: exploring cancer by systematic loss-of-function.
AB  - Cancer develops through the successive accumulation and selection of genetic and
      epigenetic alterations, enabling cells to survive, replicate and evade
      homeostatic control mechanisms such as apoptosis and antiproliferative signals.
      This transformation process, however, may create vulnerabilities since the
      accumulation of mutations can expose synthetic lethal gene interactions and
      oncogene-driven cellular reprogramming ('addiction'), giving rise to new
      therapeutic avenues. With the completion of the human genome project, it is
      anticipated that the identification and characterization of genetic networks that
      regulate cell growth, differentiation, apoptosis and transformation will be
      fundamental to decoding the complexity of these processes, and ultimately, cancer
      itself. Genomic methodologies, such as large-scale mRNA profiling using
      microarrays, have already begun to reveal the molecular basis of cancer
      heterogeneity and the clinical behavior of tumors. The combination of traditional
      cell culture techniques with high-throughput screening approaches has given rise
      to new cellular-genomics methodologies that enable the simultaneous interrogation
      of thousands of genes in live cells, facilitating true functional profiling of
      biological processes. Among these, RNA interference (RNAi) has the potential to
      enable rapid genome-wide loss-of-function (LOF) screens in mammalian systems,
      which until recently has been the sole domain of lower organisms. Here, we
      present a broad overview of this maturing technology and explore how, within
      current technical constraints, large-scale LOF use of RNAi can be exploited to
      uncover the molecular basis of cancer--from the genetics of synthetic lethality
      and oncogene-dependent cellular addiction to the acquisition of cancer-associated
      cellular phenotypes.

PMID- 15517022
TI  - RNA-interference-based functional genomics in mammalian cells: reverse genetics
      coming of age.
AB  - Sequencing of complete genomes has provided researchers with a wealth of
      information to study genome organization, genetic instability, and polymorphisms,
      as well as a knowledge of all potentially expressed genes. The identification of
      all genes encoded in the human genome opens the door for large-scale systematic
      gene silencing using small interfering RNAs (siRNAs) and short hairpin RNAs
      (shRNAs). With the recent development of siRNA and shRNA expression libraries,
      the application of RNAi technology to assign function to cancer genes and to
      delineate molecular pathways in which these genes affect in normal and
      transformed cells, will contribute significantly to the knowledge necessary to
      develop new and also improve existing cancer therapy.

PMID- 15517023
TI  - Candidemia in a Brazilian tertiary care hospital: species distribution and
      antifungal susceptibility patterns.
AB  - Recent studies have shown differences in the epidemiology of invasive infections
      caused by Candida species worldwide. In the period comprising August 2002 to
      August 2003, we performed a study in Santa Casa Complexo Hospitalar, Brazil, to
      determine Candida species distribution associated with candidemia and their
      antifungal susceptibility profiles to amphotericin B, fluconazole and
      itraconazole. Antifungal susceptibility was tested according to the broth
      microdilution method described in the NCCLS (M27A-2 method). Only one sample from
      each patient was analyzed (the first isolate). Most of the episodes had been
      caused by species other than C. albicans (51.6%), including C. parapsilosis
      (25.8%), C. tropicalis (13.3%), C. glabrata (3.3%), C. krusei (1.7%), and others
      (7.5%). Dose-dependent susceptibility to itraconazole was observed in 14.2% of
      strains, and dose-dependent susceptibility to fluconazole was found in 1.6%.
      Antifungal resistance was not found, probably related to low use of fluconazole.
      Further epidemiological surveillance is needed.

PMID- 15517025
TI  - Enteroparasitic occurrence in fecal samples analyzed at the University of Western
      Sao Paulo-UNOESTE Clinical Laboratory, Presidente Prudente, Sao Paulo State,
      Brazil.
AB  - This study aims to analyze the enteroparasitic occurrence in children from 0 to
      12 years old consulted at the University of western Sao Paulo Clinical
      Laboratory, Presidente Prudente, SP, Brazil, in relation to the socioeconomic
      profile of the attended children. Stool samples were examined and a questionnaire
      was applied with the objective of knowing the patient's age, sex, medical
      attendance, characteristic of the habitation, provisioning of water, dejection
      and domestic waste fates, use of footwear and clinical signs. The software EPI
      INFO 6 (Version 6.04b) was used for the elaboration of the data bank structure
      and analysis after previous data codification. Among 1,000 children analyzed, as
      many as 21.3% presented some kind of parasite. The most frequent protozoan was
      Giardia lamblia (7.3%) followed by Entamoeba coli (3.9%). The most frequent
      helminth was Enterobius vermicularis (1.9%) followed by Hymenolepis nana (0.5%).
      The most frequent protozoan association was Giardia lamblia / Entamoeba coli
      (0.9%).

PMID- 15517026
TI  - Dot-ELISA for the diagnosis of neurocysticercosis.
AB  - The aim of the present study was to standardize and evaluate dot-Enzyme linked
      immunosorbent assay (Dot-ELISA), a simple and rapid test for the detection of
      cysticercus antibodies in the serum for the diagnosis of neurocysticercosis
      (NCC). The antigen used in the study was a complete homogenate of Cysticercus
      cellulosae cysts obtained from infected pigs and dotted on to nitrocellulose
      membrane. Test sera were collected from the patients of NCC, and control sera
      from patients with other diseases and healthy students and blood donors of the
      Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER)
      Hospital, Pondicherry, during a study period from 2001 to 2003. Dot-ELISA
      detected antibodies in 14 of 25 (56%) in clinically suspected cases of NCC, 13 of
      23 (56.5%) in CT/MRI proven cases of NCC and 2 of 25 (8%) each in non-cysticercal
      CNS infection controls and healthy controls. The test showed a sensitivity of
      56.25%, specificity of 92%, positive predictive value of 87.09%, and negative
      predictive value of 70.76%. Results of the present study shows that the Dot-ELISA
      as a simple test can be used in the field or poorly equipped laboratories for
      diagnosis of NCC .

PMID- 15517027
TI  - Comparative study of the topical effectiveness of the Andiroba oil (Carapa
      guianensis) and DEET 50% as repellent for Aedes sp.
AB  - DEET (N,N-diethyl-3-methylbenzamide) is nowadays the most effective mosquito
      repellent available, however, its use can present some topical and systemic side
      effects. Some botanical compositions, as Andiroba (Carapa guianensis), have been
      proved repellent properties at low cost and toxicity. An experimental study was
      driven involving four volunteers submitting their forearms covered with Andiroba
      oil at 100%, DEET 50%, refined soy oil, Andiroba oil 15% and in the absence of
      products, directly to healthy females of Aedes sp. The times of first and third
      bites were checked. The results showed that the median of the first bite without
      any product was 17.5s and the third bite, 40.0s. In the soy oil, the bites
      happened in 60.0s and 101.5s, in the presence of Andiroba oil 100%, in 56.0s and
      142.5s and in Andiroba oil 15%, in 63.0s and 97.5s. The volunteers using DEET 50%
      had not received bites after 3600s in most of the experiments (p < 0.001
      Wilcoxon). Pure Andiroba oil compared to the soy oil, forearm without product and
      Andiroba oil 15%, showed discreet superiority (p < 0.001 Wilcoxon). Our
      conclusion is that this study demonstrated that the pure Andiroba oil presents
      discreet repellent effect against bite of Aedes sp., being significantly inferior
      to DEET 50%.

PMID- 15517028
TI  - Comparative morphometry and morphology of Anopheles aconitus Form B and C eggs
      under scanning electron microscope.
AB  - Comparative morphometric and morphological studies of eggs under scanning
      electron microscope (SEM) were undertaken in the three strains of two karyotypic
      forms of Anopheles aconitus, i.e., Form B (Chiang Mai and Phet Buri strains) and
      Form C (Chiang Mai and Mae Hong Son strains). Morphometric examination revealed
      the intraspecific variation with respect to the float width [36.77 +/- 2.30
      microm (Form C: Chiang Mai strain) = 38.49 +/- 2.78 microm (Form B: Chiang Mai
      strain) = 39.06 +/- 2.37 microm (Form B: Phet Buri strain) > 32.40 +/- 3.52
      microm (Form C: Mae Hong Son strain)] and number of posterior tubercles on deck
      [2.40 +/- 0.52 (Form B: Phet Buri strain) = 2.70 +/- 0.82 (Form B: Chiang Mai
      strain) < 3.10 +/- 0.32 (Form C: Chiang Mai strain) = 3.20 +/- 0.42 (Form C: Mae
      Hong Son strain)], whereas the surface topography of eggs among the three strains
      of two karyotypic forms were morphologically similar.

PMID- 15517029
TI  - Some ultrastructural superficial changes in house fly (Diptera: Muscidae) and
      blow fly (Diptera: Calliphoridae) larvae induced by eucalyptol oil.
AB  - The ultrastructural superficial changes in third instar house fly (Musca
      domestica) and blow fly (Chrysomya megacephala) induced by eucalyptol oil were
      observed using scanning electron microscopy. Dipped in 0.902 g/ml eucalyptol for
      30 sec, the larvae integument of both species showed significant aberrant
      appearance of the body surface, particularly swelling integument, bleb formation,
      partial breach and deformation of spines.

PMID- 15517031
TI  - Sanitary conditions of a colony of urban feral cats (Felis catus Linnaeus, 1758)
      in a zoological garden of Rio de Janeiro, Brazil.
AB  - The colony of urban stray cats living in the Rio de Janeiro zoological garden was
      studied in order to develop a population and health control program. As many cats
      as possible were captured during two months (47 animals) and were classified
      according to gender, age, weight and coat markings. They were submitted to a
      general health evaluation, examined for the presence of ectoparasites and sent to
      a surgical neutering program. All animals had a blood sample drawn for CBC,
      platelet count, heartworm and retroviruses detection. Capillary blood smears were
      made for hemoparasites detection. Coat marking and colors were tabby (59.7%),
      followed by solid black (17%); torbie (10.6%); bicolor (10.6%) and harlequin
      (2.1%). The only ectoparasites found were fleas, which infested 28% of the
      animals. The hemoparasites found were Haemobartonella felis (38%) and piroplasmas
      that could not be differentiated between Cytauxzoon spp. and Babesia spp. (47%).
      No cat was found infected by Dirofilaria immitis or FeLV (Feline Leukemia Virus),
      although FIV (Feline Immunodeficiency Virus) antibodies could be detected (21%).
      There was no correlation between hemoparasites and FIV infections. The estimated
      total cat population (mark-recapture method) was 59; 68% female and 32% male,
      suggesting that a neutering program is in fact needed.

PMID- 15517032
TI  - Detection of Mycobacterium leprae DNA for 36kDa protein in urine from leprosy
      patients: a preliminary report.
AB  - We have searched for Mycobacterium leprae DNA for 36kDa protein in urine using a
      M. leprae specific PCR technique. A limited number of 16 patients (of which 11
      belonged to lepromatous leprosy and five to tuberculoid leprosy) and eight
      healthy individuals were included for the present study. The number of urine
      samples positive by PCR were 36.4% (4/11) in lepromatous patients and 40% (2/5)
      in tuberculoid patients. None of the samples from healthy individuals was
      positive. To our knowledge, the results indicate, for the first time, the
      presence of M. leprae DNA in urine from leprosy patients. Another important
      finding obtained out of the study is that amongst treated patients 66.6% (4/6)
      were positive whereas amongst untreated only 20% (2/10) were positive. From the
      present indicative data it appears that treatment improves the PCR results with
      urine as a sample. Thus, the approach could prove to be useful for monitoring the
      treatment response of individual patients and needs to be further evaluated with
      a large number of patients.

PMID- 15517034
TI  - Paracoccidioidomycosis in organ transplant recipient: case report.
AB  - Paracoccidioidomycosis is a common disease in Latin America but it is rare in
      organ transplant recipient patients. We report on a case of such mycosis in a
      renal transplant recipient. The patient presented with a large lung cavity on the
      left lower lobe, a rare radiological presentation of paracoccidioidomycosis.
      Unusual clinical and radiological manifestations of Paracoccidioides brasiliensis
      infection can occur in immunocompromised patients.

PMID- 15517036
TI  - Murine (endemic) typhus in Brazil: case report and review.
AB  - Murine typhus has been increasingly recognized worldwide and is becoming a
      relevant differential diagnosis in febrile conditions. In Brazil, murine typhus
      has never received much attention. We present a recently diagnosed case and a
      literature review that suggests that the disease could be more prevalent in
      Southeastern Brazil than acknowledged until now.

PMID- 15517038
TI  - Orbital tuberculosis diagnosed by immunohistochemistry: case reports.
AB  - PURPOSE: To describe three cases of orbital tuberculosis, with their clinical
      characteristics and respective diagnostic procedures, showing the importance of
      histopathology for the correct diagnosis. PATIENTS AND METHODS: Three patients
      diagnosed and treated for orbital tuberculosis, in the "Hospital das Clinicas da
      Faculdade de Medicina da Universidade de Sao Paulo" during the years of 1999 and
      2001. RESULTS: All of the patients were female and referred a chronic evolution
      of swelling of one eyelid associated or not with other symptoms. They had not HIV
      infection. Two of them had positive epidemiology for tuberculosis. However, the
      search for systemic evidence of the disease and staining for bacilli (Ziehl
      Neelsen method) were negative in all three patients. In all the cases, only the
      biopsy with immunohistochemical analysis could confirm the diagnosis. COMMENTS:
      Orbital involvement is a rare ocular manifestation of tuberculosis. Even in a
      tertiary hospital, few cases, if any, are diagnosed per year. However, the global
      incidence and prevalence of M. tuberculosis infections is not under control yet,
      and it has been a serious public health problem. Thus, one must be aware of the
      possibility of tuberculosis among the orbital diseases.

PMID- 15517039
TI  - Erythema induratum of Bazin and renal tuberculosis: report of an association.
AB  - Erythema induratum of Bazin is a disease that usually affects women, in whom
      erythematous subcutaneous nodules and plaques appear on the posterior part of the
      lower extremities, some of which ulcerate. In many countries, tuberculosis is
      still the main etiologic factor. We report a case of a 40-year-old woman who
      presented a course of protracted and recurrent episodes over five years of
      cutaneous lesions on her legs. These tend to involute, but new crops appear at
      irregular intervals. It was painful, erythematous-violaceous nodules, some of
      which drained a reddish secretion. The histopathologic features of the lesions
      demonstrated inflammatory infiltration, with predominance of neutrophils in
      dermis and hypodermis, necrotizing vasculitis in the arterioles and septal
      fibrosis. There was no granuloma. The Ziehl-Neelsen stain did not revealed acid
      fast bacilli, and the culture of biopsy specimen was negative. The tuberculin
      skin test was strongly positive (17 mm). The chest X-ray was normal. Few months
      later she presented adynamia and urinary complaints, such as polacyuria and
      dysuria. It has been done an urynalysis, which demonstrated acid pH urine,
      sterile pyuria and microscopic hematuria. It was then raised the diagnostic
      hypothesis of renal tuberculosis. The urine culture for M. tuberculosis was
      positive in two out of ten samples. The treatment was instituted with rifampin,
      isoniazid and pyrazinamide, with complete regression. This case illustrates a
      clear association between erythema induratum and renal tuberculosis, demonstrated
      by the remission of the cutaneous lesions after the treatment of the renal
      tuberculosis.

PMID- 15517040
TI  - [Basic research in stem cell therapy--luxury or need?].

PMID- 15517037
TI  - Envenomation by neotropical opisthoglyphous colubrid Thamnodynastes cf. pallidus
      Linne, 1758 (Serpentes:Colubridae) in Venezuela.
AB  - This is a case report of a "non-venomous" snake bite in a herpetologist observed
      at the Sciences Faculty of the Universidad de los Andes (Merida, Venezuela). The
      patient was bitten on the middle finger of the left hand, and shows signs of
      pronounced local manifestations of envenomation such as bleeding from the tooth
      imprint, swelling and warmth. He was treated with local care, analgesics, and
      steroids. He was dismissed from the hospital and observed at home during five
      days with marked improvement of envenomation. The snake was brought to the
      medical consult and identified as a Thamnodynastes cf. pallidus specimen. This
      report represents the first T. pallidus accident described in a human.

PMID- 15517041
TI  - [Tetralogy of Fallot. What is the real benefit of surgical correction in the
      adult age?].

PMID- 15517043
TI  - Combined transplantation of skeletal myoblasts and mesenchymal cells
      (cocultivation) in ventricular dysfunction after myocardial infarction.
AB  - OBJECTIVE: Cell therapy in the myocardium has been mainly performed with
      satisfactory results using 2 cell types: skeletal myoblasts (myogenic) and
      mesenchymal cells (angiogenic). This study assessed the combined transplantation
      of those 2 cell types (SMM) into infarcted rats. METHODS: Myocardial infarction
      was induced by ligature of the left coronary artery in 26 Wistar rats. After one
      week, the animals underwent echocardiography for assessing ejection fraction
      (EF%) and left ventricular end-diastolic and systolic volumes (EDV, ESV, mL).
      After 2 days, the animals were reoperated on and divided into 2 groups: 1)
      control (n = 10), which received 0.15 mL of culture medium; and 2) SMM (n = 16),
      which received 7.5x10(6) heterologous skeletal myoblasts and mesenchymal cells in
      the infarcted region. The cells were obtained from puncture of the iliac crest
      and biopsy of skeletal muscle, and were cultured in vitro. After one month, the
      animals underwent a new echocardiography. RESULTS: No significant difference in
      EF, EDV, and ESV was observed between the 2 groups on baseline echocardiographic
      values. One month after transplantation, the following was observed: a reduction
      in EF in the control group (29.31 +/- 5.6% to 23.54 +/- 6.51%; P = 0.048); and an
      increase in EF in the SMM group (24.03 +/- 8.68% to 31.77 +/- 9.06%; P = 0.011).
      The presence of neovascularization and muscle fibers was identified in the
      regions of myocardial fibrosis in the SMM group. CONCLUSION: Cocultivation of
      skeletal myoblasts and mesenchymal cells is functionally effective.

PMID- 15517044
TI  - Mobility of the Septum primum does not depend on the foramen ovale diameter in
      normal fetuses.
AB  - OBJECTIVE: To test the hypothesis that a correlation exists between the maximum
      foramen ovale diastolic diameter and the excursion index (EI) of the septum
      primum in normal fetuses. METHODS: One hundred and two normal fetuses with
      gestational ages ranging from 20 to 40 weeks were submitted to echocardiography.
      The foramen ovale diameter and the "maximal excursion" of the septum primum were
      measured in a 4-chamber view. The data were analyzed by Pearson's correlation
      coefficient. RESULTS: The mean foramen ovale (FO) diameter was 5.06 +/- 1.29 mm;
      the maximal excursion of the septum primum was 5.42 +/- 1.41 mm; the left atrium
      diameter 11.47 +/- 2.76 mm; the septum primum "excursion index" was 0.48 +/-
      0.09. Mean FO/EI ratio was 11.35 +/- 3.94 mm. No FO/EI correlation (r = -0.03)
      existed, and a weak foramen ovale/left atrium correlation (r = 0.31) was
      observed, as well as a weak foramen ovale/excursion of septum primum correlation
      (r = 0.21). CONCLUSION: Septum primum mobility does not depend on the foramen
      ovale diameter in normal fetuses, suggesting that the modifications of its
      diastolic displacement is not influenced by the size of the interatrial opening.

PMID- 15517042
TI  - Cryopreserved aortic homograft for aortic valve replacement: immediate results.
AB  - OBJECTIVE: To assess immediate clinical and echocardiographic results of the use
      of cryopreserved aortic homografts for aortic valve replacement. METHODS:
      Eighteen patients with aortic valve disease underwent aortic valve replacement,
      receiving a cryopreserved aortic homograft, 15 were male, 10 had aortic
      regurgitation, and 8 had aortic stenosis. Age ranged from 18 to 65 years (mean,
      44.5 +/- 18.14 years). Four patients had infective endocarditis, 12 patients were
      in functional class II, and 6 patients were in functional class III (NYHA). Left
      ventricular function was normal in 15 patients. RESULTS: Hospital mortality was
      5.5% (1 patient) due to respiratory distress; the other patients were discharged
      from the hospital between the fifth and eighth postoperative days in functional
      class I. Maximal aortic transvalvular gradient, on echocardiography, ranged from
      0 to 30 mmHg, with a mean of 10.9 +/- 9.2 mmHg. Five patients did not have any
      degree of regurgitation through the aortic homograft, 11 patients (61.1%) had
      minimal regurgitation, and 2 had mild regurgitation. Duration of extracorporeal
      circulation ranged from 130 to 220 minutes (mean, 183.9 +/- 36.7 minutes).
      Duration of aortic clamping ranged from 102 to 168 minutes (mean, 139.14 +/-
      25.10 minutes). Bleeding in the postoperative period ranged from 210 to 1220 mL,
      with a mean of 511.4 +/- 335.1 mL. Reoperations were not necessary. Duration of
      orotracheal intubation ranged from 2 hours 50 minutes to 17 hours with a mean of
      9.14 +/- 3.6 hours. CONCLUSION: Cryopreserved aortic homografts may be routinely
      used with low hospital morbidity and mortality.

PMID- 15517045
TI  - Complications of hypertension in men and women seen in a referral outpatient care
      unit.
AB  - OBJECTIVE: To assess the association between sex and left ventricular
      hypertrophy, stroke, and renal failure in hypertensive patients in a referral
      outpatient care unit. METHODS: This study assessed 622 hypertensive patients
      diagnosed with left ventricular hypertrophy based on electrocardiography, renal
      failure based on serum creatinine level > or = 1.4 mg/dL, and stroke based on a
      previous history and physical examination. Logistic regression was used to
      estimate the odds ratio of the association between sex and target-organ lesions
      in hypertension adjusted for race, age, and duration of the disease. RESULTS: The
      mean age of the patients was 48.4 +/- 13.8 years; 74.1% were women, and 84.9%
      were mulattos or blacks. Almost half of the men and more than 40% of the women
      had had at least 1 definite event involving a target-organ lesion. The incidence
      of renal failure was greater among men [adjusted OR (ORa) = 2.73, P= 0.002]. In
      white patients, the incidence of stroke was significantly (P= 0.017) greater
      among men (4/33) than among women (0/56), and, in the age group > or = 49 years,
      the prevalence of left ventricular hypertrophy was significantly greater among
      men (ORa = 1.99, P= 0.024). CONCLUSION: The data obtained suggest a greater
      prevalence of renal failure in men than in women, of stroke in white men than in
      white women, and of left ventricular hypertrophy in men than in women aged 49
      years and above.

PMID- 15517046
TI  - Assessment of the ventricular function of patients with advanced chronic
      obstructive pulmonary disease by using magnetic resonance imaging.
AB  - OBJECTIVE: To assess the mechanisms that may be involved in the evolution of
      right and left ventricular dysfunction in patients with chronic obstructive
      pulmonary disease (COPD). METHODS: Magnetic resonance imaging was used in 11
      control patients (group C) and 27 patients with COPD, who were divided into 2
      groups, COPDc and COPDs, according to the presence or absence of right
      ventricular dysfunction, respectively. Doppler echocardiography was used for
      assessing the degree of pulmonary hypertension. RESULTS: The right ventricular
      diameter was similar in the 3 groups, COPDs, COPDc and C (29+/-8 mm; 31+/-7 mm;
      and 30+/-6 mm; respectively, P=NS). Right ventricular hypertrophy was observed
      only in the COPD groups (8+/-2 mm and 9+/-3 mm vs 5+/-1 mm; P<0.01). The
      percentage of systolic right ventricular lateral wall thickening (%RVLWT) in the
      3 groups were as follows: 86+/-82% vs 41+/-35% vs 86+/-89%; P=NS). Different left
      ventricular ejection fractions were observed in the groups as follows: 69+/-9% vs
      55+/-16% vs 76+/-6%; P < 0.01. A positive and significant linear correlation was
      observed between the left ventricular (LV) diastolic diameter and the LV systolic
      volume (r = 0.72; P < 0.01). No correlation was observed between the pulmonary
      volumes, arterial blood gas analysis, and ventricular function. CONCLUSION: No
      correlation was observed between the severity of pulmonary function and the
      degree of ventricular function impairment. Whether a preserved %RVLWT means the
      possibility of reversibility of right ventricular function remains to be
      elucidated. However, the presence of the phenomenon of ventricular
      interdependence was confirmed.

PMID- 15517047
TI  - Myocardial revascularization surgery without extracorporeal circulation minimizes
      postoperative bleeding and the need for transfusion.
AB  - OBJECTIVE: To compare myocardial revascularization (MR) with and without
      extracorporeal circulation (ECC) in regard to postoperative bleeding and the need
      for blood and hemoderivate transfusion. METHODS: From November 2001 to February
      2002, 186 patients undergoing myocardial revascularization were assessed,
      excluding those who underwent associated procedures. The patients were divided
      into 2 groups as follows: group A -- comprising 116 patients undergoing MR with
      ECC; and group B -- comprising 69 patients undergoing MR without ECC. Both groups
      were comparable in regard to pre- and intraoperative characteristics, except for
      the greater number of distal anastomoses (P=0.0004) in group A, and greater
      prothrombin activity (P=0.04) and INR (P=0.03) in group B. To avoid discrepancies
      between the groups, 140 patients with statistically similar characteristics were
      selected. RESULTS: Studying the paired groups, both the total bleeding volume in
      24 hours (P=0.001) and the bleeding volume indexed for body surface (P=0.004)
      were greater in group A (609.6 +/- 395.8 mL; 331.8 +/- 225.8 mL/m2, respectively)
      than in group B (437.2 +/- 315 mL; 241 +/- 173.9 mL/m2, respectively). Although
      the need for transfusion was not significantly different between the groups
      (P=0.1), the amount of erythrocyte concentrate transfused was greater in group A
      (P=0.01). No statistical difference was observed in regard to transfusion of
      other hemocomponents and the need for surgical review of hemostasis. CONCLUSION:
      Myocardial revascularization without ECC was more advantageous than MR with ECC
      in regard to smaller postoperative blood loss and a lesser need for transfusion
      of erythrocyte concentrate. The repercussions of this finding may be innumerable,
      particularly in regard to minimization of morbid factors and hospital costs.

PMID- 15517048
TI  - Acute myocarditis secondary to pheochromocytoma.

PMID- 15517049
TI  - Stem cell therapy with retrograde coronary perfusion in acute myocardial
      infarction. A new technique.

PMID- 15517050
TI  - [Evidence based cardiology].

PMID- 15517051
TI  - [Evidence based cardiology. Some necessary clarifications].

PMID- 15517052
TI  - [Case 05/2004 - Sudden death after severe dyspnea in a 70-year-old woman with
      coronary artery disease and hypertension (Instituto do Coracao do Hospital das
      Clinicas da FMUSP)].

PMID- 15517055
TI  - [Supporting mental health research publications from low- and middle-income
      countries].

PMID- 15517056
TI  - [Binge eating disorder: an emerging entity that responds to pharmacotherapy].

PMID- 15517057
TI  - [Psychodynamic group treatment for generalized social phobia].
AB  - OBJECTIVES: The aim of this study is to assess the effectiveness of psychodynamic
      group therapy in patients with generalized social phobia. METHODS: Thirty
      patients were included in a randomized single-blind clinical trial comparing
      psychodynamic group treatment (PGT) with a credible placebo control group (CPC).
      PGT was carried out within a 12-session psychodynamically-oriented group
      psychotherapy. Control patients received a treatment package of lecture
      discussion and support group for 12 weeks which was compared to PGT. Each
      participant completed the Liebowitz Social Anxiety Scale (LSAS), the Hamilton
      Anxiety Scale (HAS) and the Clinical Global Impression Scale(CGI) at pretreatment
      assessment and after 12 weeks of treatment. Data analysis was carried out using a
      repeated measures ANOVA. Patients were excluded if they were under any kind of
      pharmacotherapy or psychotherapic treatment. RESULTS: Both groups demonstrated
      significant pretreatment-to-posttreatment change on most measures. On the LSAS,
      PGT patients were rated as more improved than controls at posttest assessment
      (F(1,28)=4.84, p=0.036). Baseline data of completers did not show differences
      between both groups in the demographic variables and outcome variables used.
      CONCLUSIONS: The present study showed that PGT was [corrected] superior to a
      credible placebo control group in the treatment of generalized social phobia, in
      a 12-week randomized single-blind clinical trial.

PMID- 15517058
TI  - [Religion and drug use by adolescents].
AB  - INTRODUCTION: Many international studies show that religion is an important
      dimension modulating the use of alcohol and drugs by adolescents. OBJECTIVES: to
      determine which religious variables are associated to frequent or heavy use of
      alcohol, tobacco and drugs among adolescents in intermediate and high schools in
      Campinas, Brazil. METHODS: A cross-sectional study using a self-report anonymous
      questionnaire was administered to 2,287 students from a convenience sample of
      seven schools: five from central areas (two public and three private schools) and
      two public schools from the outskirts of the city, in 1998. The study analyzes
      data regarding the use of alcohol, tobacco, medicines, solvents, marijuana,
      cocaine and ecstasy. The religious variables included in the regression analysis
      were: religious affiliation, church attendance, self-assessed religiousness, and
      religious education in childhood. For the substances, nicotine, alcohol,
      marijuana, cocaine, ecstasy and "abuse of medicines" a logistic regression
      analysis for dicotomic answer was applied. RESULTS: The heavy use of at least one
      drug during the last month was more frequent among students that did not have a
      religious education during childhood. The use in the last month of cocaine,
      ecstasy and (abuse of) medicines was more frequent among those students that had
      no religion (cocaine and medicines) and that did not have a religious education
      during childhood (ecstasy and medicines). CONCLUSIONS: this study is consistent
      with previous investigations demonstrating a strong influence of religious
      variables over the use of drugs among adolescents. Interesting, it was found that
      no or weaker religious education during childhood was markedly associated with
      significant more use of drugs during adolescence.

PMID- 15517059
TI  - [Factor structure of the Stages of Change Readiness and Treatment Eagerness Scale
      (SOCRATES) in alcohol dependent outpatients].
AB  - OBJECTIVE: The aim of this study was to investigate the reliability and factor
      structure of the Stages of Change Readiness and Treatment Eagerness Scale
      (SOCRATES), version 8, a 19-item self-reported instrument developed to measure
      readiness to change in alcohol-dependent alcoholics. METHODS: A Confirmatory
      Factor analysis of the SOCRATES was performed based on the factor structures
      previously demonstrated by Miller & Tonigan and Maisto et al. in a sample with
      326 alcohol-dependent outpatients. The questionnaire was translated into
      Portuguese, cross-culturally adapted and back-translated into English. During
      this process SOCRATES underwent some modifications to simplify some complex
      question formats. RESULTS: The analysis showed that two correlated factors
      provided the best fit for the data and that these were similar to Maisto et al.'s
      factors. CONCLUSIONS: There was less evidence to support a three-factor
      structure. The results are compared to previous studies and the reasons for
      discrepancies are discussed.

PMID- 15517060
TI  - [Transcranial Magnetic Stimulation in depression: results of bi-weekly
      treatment].
AB  - OBJECTIVE: Transcranial Magnetic Stimulation (TMS) has been shown to be a useful
      therapy for depression. This paper evaluates the results of bi-weekly low
      frequency TMS of 4 weeks duration, in 10 patients with depression who do not
      respond or are intolerant to antidepressive medication. METHODS: This is a case
      series study. DMS-IV criteria were used to diagnose depression. In order to
      disclose possible improvements in depressive symptoms, the 17 items Hamilton
      scale was used at three different moments: at the beginning, middle and end of
      the treatment period. Results were analysed using Friedman's chi2 test. RESULTS:
      Hamilton's scale score improvement was > 50% in five patients and > 75% in 3 of
      these. CONCLUSIONS: TMS may be efficacious, safe and easily performed as an
      adjunct to medical treatment of depression. We cannot differentiate a
      potentiation of the effect of antidepressive medication from an intrinsic effect
      of TMS alone, since we did not treat any subjects without the concurrent use of
      medication.

PMID- 15517061
TI  - [Neuropsychological impairments in crack cocaine-dependent inpatients:
      preliminary findings].
AB  - OBJECTIVE: Although cocaine use is a significant public health problem, there is
      relative paucity of scientific data on long-term neurocognitive consequences of
      the exposure to the substance. METHODS: This study examined the association
      between crack cocaine dependence and neuropsychological performance. An extended
      battery of neuropsychological tests was administered to 15 abstinent cocaine
      abusers, inpatients in abstinence for two weeks, and 15 non-drug-using control
      subjects matched for age, gender, education, socio-economic status, handedness
      and IQ. RESULTS: The preliminary findings showed statistical significance
      (p<0.05) on differences of performance in attention, verbal fluency, verbal
      memory, visual memory, learning ability and executive functions. CONCLUSIONS:
      These results represent evidences that cocaine abuse is associated with
      decrements in cognitive functioning, similar to cognitive disorders associated to
      prefrontal and temporal brain impairments. Knowledge of specific cognitive
      deficits in cocaine abusers may be useful for designing more effective substance
      abuse prevention and treatment programs.

PMID- 15517062
TI  - [Neuropsychology of eating disorders: a systematic review of the literature].
AB  - BACKGROUND: The pathophysiology of eating disorders is still unknown, with many
      factors possibly involved. The existence of a central nervous system (CNS)
      dysfunction is being investigated with particular interest. One of the most
      employed strategies to reach this goal is the evaluation of cognitive functioning
      of patients with eating disorders with neuropsychological tests. OBJECTIVE: To
      evaluate the current knowledge about the neuropsychology of ED. METHODS: We
      performed a review of several data bases (including MedLINE, PsychoINFO, LILACS
      and Cochrane Data Bank), using terms related to main theme of interest. The
      review comprised articles published up to January, 2004. RESULTS: Anorexia
      Nervosa (AN) was the most studied ED from the neuropsychological point-of-view,
      with studies tending to elicit attentive, visuo-spatial, and visuo-constructive
      deficits among such patients. On the other side, patients with Bulimia Nervosa
      (BN) exhibited deficits in the selective aspects of attention and in executive
      functions. As yet, there is no study covering the neuropsychological aspects of
      binge-eating disorder. After successful treatment, individuals show improvement
      of some cognitive deficits, while other seem to persist. CONCLUSIONS: The ED are
      possibly associated with a certain degree of neuropsychological dysfunction, even
      though there is no consensus with regard to which function is particularly
      impaired. The fact that some cognitive dysfunction tend to disappear after
      treatment argues in favor of the hypothesis that these are functional deficits.
      Other deficits, however, tend to persist, suggesting that they may precede the
      development of eating disorders or even contribute to their development or to a
      worse prognosis. The study of the neuropsychological aspects of ED may help
      tailoring more selective therapeutic approaches to patients suffering from these
      disorders.

PMID- 15517063
TI  - [The integration of psychopharmacotherapy and psychoanalytical psychotherapy: a
      critical review].
AB  - OBJECTIVE: Integration between psychotherapy and psychopharmacotherapy has been a
      conflicting subject in the history of psychiatry. To date, dichotomy between
      "biological" and "psychological" models is noticed, although recent studies have
      been showing the importance of the association of these modalities in the current
      psychiatric practice. This study attempts to review psychodynamic, technical, and
      other issues involving the integration of pharmacological and psychotherapeutical
      treatments. METHODS: Literature search was based on MEDLINE, PsychoINFO and
      Lilacs, referring to the period from 1966 to September 2002. RESULTS: The studies
      reviewed demonstrated that the application of combined treatment might be
      positive. CONCLUSIONS: The efficacy of the combined treatment depends on the
      capacity of the integration of the different forms of treatment. More research is
      necessary in this area.

PMID- 15517064
TI  - [Interpersonal Therapy: a brief and focal model].
AB  - Psychotherapy is a particular form of treatment in Psychiatry. Its use is
      widespread and has many different approaches. OBJECTIVE: In this article, the
      author makes some considerations about Interpersonal Therapy (IPT), a brief and
      focal psychotherapy. Initially created to treat depression, other researchers had
      successfully increase its spectrum. It could be divided in three phases. Initial,
      when the therapist makes the diagnosis of the disorder and also the interpersonal
      problematic is pointed out; the patient received a sick role. Intermediary when
      the focus is treated, and the final phase when the therapist encourages the
      patient to recognize and consolidate gains and prepare the patient to use it in
      the future. METHODS: It is stressed that IPT is a testable form of psychotherapy
      and the scientific evidences of its efficacy are showed. CONCLUSIONS: The results
      assure that IPT is an efficient form of psychotherapy for depression with a great
      acceptability from the patients.

PMID- 15517065
TI  - [Transcranial magnetic stimulation: review of accidental seizures].
AB  - Transcranial magnetic stimulation (TMS) is a new technique that has been used for
      the treatment of neuropsychiatric disorders, specially depression. It uses a
      magnetic stimulator that generates a magnetic field that is applied over the
      patient's skull with a coil. Possible seizures may be induced accidentally by
      TMS. TMS is usually used with sub threshold stimuli and seizures may occur by
      chance, especially when over the safety parameters. This article reviews the
      eight cases of undesirable seizures occurred with rTMS The possible mechanisms of
      seizure induction and the patients profile with a higher risk of convulsion are
      also described.

PMID- 15517067
TI  - [The value of publishing negative results from a randomized controlled trial: the
      Rosenheck's study].

PMID- 15517068
TI  - [Use of fluoxetine in somatic delusional disorder].

PMID- 15517069
TI  - [Who suffers the impact: some observations on health].

PMID- 15517070
TI  - [A comment on the editorial Cannabis use in adolescence and risk of
      schizophrenia].

PMID- 15517071
TI  - [Use of gabapentin in group B -- DSM-IV personality disorders].

PMID- 15517072
TI  - Leishmania infantum heat shock protein 83 for the serodiagnosis of tegumentary
      leishmaniasis.
AB  - The serologic assay is an important tool in the diagnosis of leishmaniasis. One
      of the most commonly used tests is enzyme-linked immunosorbent assay (ELISA).
      Since total Leishmania promastigotes are used as antigen in the routine assay,
      false-positive reactions are frequent due to cross-reaction with sera from other
      diseases, mainly Chagas' disease. Therefore, an antigen that determines less
      cross-reactivity has been pursued for the serodiagnosis of leishmaniasis. In the
      present study we analyzed the use of recombinant Leishmania infantum heat shock
      protein (Hsp) 83 in ELISA for the serodiagnosis of cutaneous (N = 12) and
      mucocutaneous leishmaniasis (N = 14) and we observed the presence of anti-L.
      infantum Hsp 83 antibodies in all samples as well as anti-Leishmania total
      antigen antibodies. When cross-reactivity was tested, chronic Chagas' disease
      patients (N = 10) did not show any reactivity. Therefore, we consider this L.
      infantum Hsp 83 to be a good antigen for routine use for serodiagnosis of
      tegumentary leishmaniasis.

PMID- 15517073
TI  - Bioelectrical impedance spectroscopy for the assessment of body fluid volumes of
      term neonates.
AB  - The assessment of fluid volume in neonates by a noninvasive, inexpensive, and
      fast method can contribute significantly to increase the quality of neonatal
      care. The objective of the present study was to calibrate an acquisition system
      and software to estimate the bioelectrical impedance parameters obtained by a
      method of bioelectrical impedance spectroscopy based on step response and to
      develop specific equations for the neonatal population to determine body fluid
      compartments. Bioelectric impedance measurements were performed by a laboratory
      homemade instrument. The volumes were estimated in a clinical study on 30 full
      term neonates at four different times during the first month of life. During the
      first 24 hours of life the total body water, extracellular water and
      intracellular water were 2.09 +/- 0.25, 1.20 +/- 0.19, and 0.90 +/- 0.25 liters,
      respectively. By the 48th hour they were 1.87 +/- 0.27, 1.08 +/- 0.17, and 0.79
      +/- 0.21 liters, respectively. On the 10th day they were 2.02 +/- 0.25, 1.29 +/-
      0.21, and 0.72 +/- 0.14 liters, respectively, and after 1 month they were 2.34 +/
      0.27, 1.62 +/- 0.20, and 0.72 +/- 0.13 liters, respectively. The behavior of the
      estimated volume was correlated with neonatal body weight changes, leading to a
      better interpretation of such changes. In conclusion, this study indicates the
      feasibility of bioelectrical impedance spectroscopy as a method to help fluid
      administration in intensive care neonatal units, and also contribute to the
      development of new equations to estimate neonatal body fluid contents.

PMID- 15517074
TI  - Superoxide release and cellular gluthatione peroxidase activity in leukocytes
      from children with persistent asthma.
AB  - Asthma is an inflammatory condition characterized by the involvement of several
      mediators, including reactive oxygen species. The aim of the present study was to
      investigate the superoxide release and cellular glutathione peroxidase (cGPx)
      activity in peripheral blood granulocytes and monocytes from children and
      adolescents with atopic asthma. Forty-four patients were selected and classified
      as having intermittent or persistent asthma (mild, moderate or severe). The
      spontaneous or phorbol myristate acetate (PMA, 30 nM)-induced superoxide release
      by granulocytes and monocytes was determined at 0, 5, 15, and 25 min. cGPx
      activity was assayed spectrophotometrically. The spontaneous superoxide release
      by granulocytes from patients with mild (N = 15), moderate (N = 12) or severe (N
      = 6) asthma was higher at 25 min compared to healthy individuals (N = 28, P <
      0.05, Duncan test). The PMA-induced superoxide release by granulocytes from
      patients with moderate (N = 12) or severe (N = 6) asthma was higher at 15 and 25
      min compared to healthy individuals (N = 28, P < 0.05 in both times of
      incubation, Duncan test). The spontaneous or PMA-induced superoxide release by
      monocytes from asthmatic patients was similar to healthy individuals (P > 0.05 in
      all times of incubation, Duncan test). cGPx activity of granulocytes and
      monocytes from patients with persistent asthma (N = 20) was also similar to
      healthy individuals (N = 10, P > 0.05, Kruskal-Wallis test). We conclude that,
      under specific circumstances, granulocytes from children with persistent asthma
      present a higher respiratory burst activity compared to healthy individuals.
      These findings indicate a risk of oxidative stress, phagocyte auto-oxidation, and
      the subsequent release of intracellular toxic oxidants and enzymes, leading to
      additional inflammation and lung damage in asthmatic children.

PMID- 15517075
TI  - Pressure and time dependence of the cardiopulmonary reflex response in patients
      with hypertensive cardiomyopathy.
AB  - The first minutes of the time course of cardiopulmonary reflex control evoked by
      lower body negative pressure (LBNP) in patients with hypertensive cardiomyopathy
      have not been investigated in detail. We studied 15 hypertensive patients with
      left ventricular dysfunction (LVD) and 15 matched normal controls to observe the
      time course response of the forearm vascular resistance (FVR) during 3 min of
      LBNP at -10, -15, and -40 mmHg in unloading the cardiopulmonary receptors.
      Analysis of the average of 3-min intervals of FVR showed a blunted response of
      the LVD patients at -10 mmHg (P = 0.03), but a similar response in both groups at
      -15 and -40 mmHg. However, using a minute-to-minute analysis of the FVR at -15
      and -40 mmHg, we observed a similar response in both groups at the 1st min, but a
      marked decrease of FVR in the LVD group at the 3rd min of LBNP at -15 mmHg (P =
      0.017), and -40 mmHg (P = 0.004). Plasma norepinephrine levels were analyzed as
      another neurohumoral measurement of cardiopulmonary receptor response to LBNP,
      and showed a blunted response in the LVD group at -10 (P = 0.013), -15 (P =
      0.032) and -40 mmHg (P = 0.004). We concluded that the cardiopulmonary reflex
      response in patients with hypertensive cardiomyopathy is blunted at lower levels
      of LBNP. However, at higher levels, the cardiopulmonary reflex has a normal
      initial response that decreases progressively with time. As a consequence of the
      time-dependent response, the cardiopulmonary reflex response should be measured
      over small intervals of time in clinical studies.

PMID- 15517076
TI  - A functional study of caustic strictures of the esophagus in children.
AB  - The objective of the present study was to assess esophageal motor function in 21
      children (7.5 +/- 2.9 years) with caustic strictures. Esophageal manometry was
      performed using a water-infusion system interfaced with a polygraph and displayed
      on a computer screen. The data were compared with those obtained from 9 healthy
      children. Radionuclide transit was determined by studying deglutition of a single
      bolus of 99mTc pertechnetate in 10 ml of water. Non-peristaltic low-amplitude and
      long-duration waves were the most common findings detected in patients with
      strictures longer than 20% of esophageal length (N = 11). Compared with the
      control group, these patients presented lower mean amplitude and longer mean
      duration of waves (24.4 +/- 11.2 vs 97.9 +/- 23.7 mmHg, P < 0.05, and 6.7 +/- 2.4
      vs 1.6 +/- 0.1 s, P < 0.05, respectively). Six patients presented low-amplitude
      waves just below the constricted site. Ten children presented delayed esophageal
      transit. There was an association between dysphagia and abnormalities on
      manometry (P = 0.02) and between symptoms and scintigraphy data (P = 0.01).
      Dysphagia in caustic strictures is due to esophageal motility abnormalities,
      which are closely related to the scarred segment.

PMID- 15517077
TI  - Morphological and functional alterations of the intestine of rats with iron
      deficiency anemia.
AB  - The present study was designed to assess the intestinal absorption of D-xylose
      and jejunal morphometry in rats with iron-deficiency anemia. Male Wistar rats
      were randomly divided into a control group (diet containing 50 mg Fe/kg, N = 12)
      and an anemic group (diet containing <5 mg Fe/kg, N = 12). The animals were
      housed in individual metabolic cages and deionized water and diet were provided
      ad libitum for 6 weeks. Hemoglobin and hematocrit were determined at 0, 2, 4, and
      6 weeks. At the end of the study the rats were submitted to a D-xylose absorption
      test (50 mg/100 g body weight) and sacrificed and a jejunal specimen was obtained
      for morphometric study. At the end of the study the hemoglobin and hematocrit of
      the anemic rats (8.7 +/- 0.9 g/dl and 34.1 +/- 2.9%, respectively) were
      significantly (P < 0.05) lower than those of the controls (13.9 +/- 1.4 g/dl and
      47.1 +/- 1.5%, respectively). There was no statistical difference in D-xylose
      absorption between the anemic (46.5 +/- 7.4%) and control (43.4 +/- 9.0%) groups.
      The anemic animals presented statistically greater villus height (445.3 +/- 36.8
      microm), mucosal thickness (614.3 +/- 56.3 microm) and epithelial surface (5063.0
      +/- 658.6 microm) than control (371.8 +/- 34.3, 526.7 +/- 62.3 and 4401.2 +/-
      704.4 microm, respectively; P < 0.05). The increase in jejunum villus height,
      mucosal thickness and epithelial surface in rats with iron-deficiency anemia
      suggests a compensatory intestinal mechanism to increase intestinal iron
      absorption.

PMID- 15517078
TI  - Effects of metformin treatment on luteal phase progesterone concentration in
      polycystic ovary syndrome.
AB  - The causes of luteal phase progesterone deficiency in polycystic ovary syndrome
      (PCOS) are not known. To determine the possible involvement of hyperinsulinemia
      in luteal phase progesterone deficiency in women with PCOS, we examined the
      relationship between progesterone, luteinizing hormone (LH) and insulin during
      the luteal phase and studied the effect of metformin on luteal progesterone
      levels in PCOS. Patients with PCOS (19 women aged 18-35 years) were treated with
      metformin (500 mg three times daily) for 4 weeks prior to the test cycle and
      throughout the study period, and submitted to ovulation induction with clomiphene
      citrate. Blood samples were collected from control (N = 5, same age range as PCOS
      women) and PCOS women during the late follicular (one sample) and luteal (3
      samples) phases and LH, insulin and progesterone concentrations were determined.
      Results were analyzed by one-way analysis of variance (ANOVA), Duncan's test and
      Karl Pearson's coefficient of correlation (r). The endocrine study showed low
      progesterone level (4.9 ng/ml) during luteal phase in the PCOS women as compared
      with control (21.6 ng/ml). A significant negative correlation was observed
      between insulin and progesterone (r = -0.60; P < 0.01) and between progesterone
      and LH (r = -0.56; P < 0.05) concentrations, and a positive correlation (r =
      0.83; P < 0.001) was observed between LH and insulin. The study further
      demonstrated a significant enhancement in luteal progesterone concentration
      (16.97 ng/ml) in PCOS women treated with metformin. The results suggest that
      hyperinsulinemia/insulin resistance may be responsible for low progesterone
      levels during the luteal phase in PCOS. The luteal progesterone level may be
      enhanced in PCOS by decreasing insulin secretion with metformin.

PMID- 15517079
TI  - Relationship between the prevalence of anti-glutamic acid decarboxylase
      autoantibodies and duration of type 1 diabetes mellitus in Brazilian patients.
AB  - The objective of the present study was to determine whether the duration of
      disease has any influence on the prevalence of glutamic acid decarboxylase
      autoantibodies (GADA) in Brazilian patients with type 1 diabetes (T1D) and
      variable disease duration. We evaluated 83 patients with T1D. All participants
      were interviewed and blood was obtained for GADA measurement by a commercial
      radioimmunoassay (RSR Limited, Cardiff, UK). Four groups of patients were
      established according to disease duration: A) 1-5 years of disease (N = 24), B) 6
      10 years of disease (N = 19), C) 11-15 years of disease (N = 25), and D) >15
      years of disease (N = 15). GADA prevalence and its titers were determined in each
      group. GADA was positive in 38 patients (45.8%) and its frequency did not differ
      between the groups. The prevalence was 11/24 (45.8%), 8/19 (42.1%), 13/25 (52%),
      and 6/15 (40%) in groups A, B, C, and D, respectively (P = 0.874). Mean GADA
      titer was 12.54 +/- 11.33 U/ml for the sample as a whole and 11.95 +/- 11.8,
      12.85 +/- 12.07, 10.57 +/- 8.35, and 17.45 +/- 16.1 U/ml for groups A, B, C, and
      D, respectively (P = 0.686). Sex, age at diagnosis or ethnic background had no
      significant effect on GADA (+) frequency. In conclusion, in this transversal
      study, duration of disease did not affect significantly the prevalence of GADA or
      its titers in patients with T1D after one year of diagnosis. This was the first
      study to report this finding in the Brazilian population.

PMID- 15517080
TI  - Temperature, air pollution, and mortality from myocardial infarction in Sao
      Paulo, Brazil.
AB  - An increase in daily mortality from myocardial infarction has been observed in
      association with meteorological factors and air pollution in several cities in
      the world, mainly in the northern hemisphere. The objective of the present study
      was to analyze the independent effects of environmental variables on daily counts
      of death from myocardial infarction in a subtropical region in South America. We
      used the robust Poisson regression to investigate associations between weather
      (temperature, humidity and barometric pressure), air pollution (sulfur dioxide,
      carbon monoxide, and inhalable particulate), and the daily death counts
      attributed to myocardial infarction in the city of Sao Paulo in Brazil, where
      12,007 fatal events were observed from 1996 to 1998. The model was adjusted in a
      linear fashion for relative humidity and day-of-week, while nonparametric
      smoothing factors were used for seasonal trend and temperature. We found a
      significant association of daily temperature with deaths due to myocardial
      infarction (P < 0.001), with the lowest mortality being observed at temperatures
      between 21.6 and 22.6 degrees C. Relative humidity appeared to exert a protective
      effect. Sulfur dioxide concentrations correlated linearly with myocardial
      infarction deaths, increasing the number of fatal events by 3.4% (relative risk
      of 1.03; 95% confidence interval = 1.02-1.05) for each 10 microg/m(3) increase.
      In conclusion, this study provides evidence of important associations between
      daily temperature and air pollution and mortality from myocardial infarction in a
      subtropical region, even after a comprehensive control for confounding factors.

PMID- 15517081
TI  - Cytokine profile and nitric oxide levels in sera from patients with brucellosis.
AB  - The aims of this study were to investigate the serum levels of some cytokines
      [tumor necrosis factor-alpha (TNF-alpha), interleukin 1beta (IL-1beta), IL-2R, IL
      6, and IL-8] and nitric oxide (NO) levels in patients with untreated brucellosis
      and to test the correlation of these parameters with each other. The study was
      conducted on 67 subjects, 37 patients with brucellosis and 30 healthy individuals
      with no history of Brucella infection. Brucellosis was identified by a positive
      blood culture and/or increased Brucella antibodies in serological tests in
      addition to compatible clinical symptoms. Cytokine profile analysis was performed
      by the immulite chemiluminescent enzyme immunometric assay whose inter- and intra
      assay coefficients of variance were 2.6-3.6 and 4.4-8.5%, respectively. The
      levels of nitrites/nitrates, which are representative of NO levels, were measured
      by the Griess method. Patients with brucellosis had significantly elevated serum
      levels of nitrites/nitrates, IL-2R, IL-6 and IL-8 (mean +/- SD, 102.8 +/- 23.8
      micromol/l, 806.1 +/- 58.5 U/ml, 21.1 +/- 2.3 pg/ml, and 8.8 +/- 1.6 pg/ml,
      respectively) compared to healthy controls, whereas TNF-alpha and IL-1beta levels
      were unchanged. No statistically significant correlation was detected between any
      of the studied cytokine levels and nitrate/nitrite concentrations according to
      Pearson's linear correlation test. We conclude that only IL-6, IL-8 and IL-2R are
      elevated in brucellosis and the extent of elevation depends on the severity and
      clinical pattern of the disease. Moderate elevation in serum NO was comparable to
      that observed in previous studies. This explains the absence or very rare
      occurrence of septic shock in brucellosis.

PMID- 15517082
TI  - Absence of hepatitis B virus DNA in patients with hepatitis C and non-A-E
      hepatitis in the State of Sao Paulo, Brazil.
AB  - Occult hepatitis B virus (HBV) infection has been reported as cases in which HBV
      DNA was detected despite the absence of any HBV serological markers or in cases
      in which anti-HBc antibody was the sole marker. The aim of the present study was
      to determine, using the polymerase chain reaction (PCR), whether HBV infection
      occurs in hepatitis C and non-A-E hepatitis patients without serological evidence
      of hepatitis B infection in Sao Paulo State. Two different populations were
      analyzed: 1) non-A-E hepatitis patients, including 12 patients with acute and 50
      patients with chronic hepatic disorders without serological evidence of infection
      with known hepatitis viruses; 2) 43 patients previously diagnosed as hepatitis C
      with positive results for anti-HCV and HCV RNA. Among hepatitis C patients, anti
      HBc was detected in 18.6% of the subjects. Three different sets of primers were
      employed for HBV DNA detection by nested PCR, covering different HBV genes: C, S
      and X. HBV-DNA was not detected in any sample, whereas the positive controls did
      produce signals. The lack of HBV DNA detection with these pairs of primers could
      be due to a very low viral load or to the presence of mutations in their
      annealing sites. The latter is unlikely as these primers were screened against an
      extensive dataset of HBV sequences. The development of more sensitive methods,
      such as real time PCR, to detect circular covalent closed DNA is necessary in
      order to evaluate this question since previous studies have shown that cryptic
      hepatitis B might occur.

PMID- 15517083
TI  - Enterococcus gallinarum carrying the vanA gene cluster: first report in Brazil.
AB  - In 2000, Enterococcus faecalis resistant to vancomycin was first reported at a
      tertiary hospital in Porto Alegre, southern Brazil. The resistance spread to
      other hospitals and surveillance programs were established by hospital infection
      committees to prevent the spread of vancomycin-resistant enterococci. In February
      2002, an isolate initially identified at the genus level as Enterococcus was
      obtained by surveillance culture (rectal swab) from a patient admitted to a
      hospital for treatment of septic arthritis in the shoulder. The isolate proved to
      be resistant to vancomycin by the disc diffusion method and confirmed by an E
      test resulting in a minimal inhibitory concentration of > or = 256 microg/ml.
      This isolate was sent to a reference laboratory (Laboratorio Especial de
      Bacteriologia e Epidemiologia Molecular, Faculdade de Ciencias Farmaceuticas de
      Ribeirao Preto, USP) for further study and proved to be an E. gallinarum by the
      polymerase chain reaction (PCR) using specific primers for the species. Due to
      the phenotype of unusually high vancomycin resistance, the isolate presumably had
      the resistance genes (vanA and vanB) and this was confirmed by PCR, which
      indicated the presence of the vanA gene. A 10.8-kb Tn1546-related transposon was
      also identified by long-PCR. Interspecies transfer of the vancomycin-resistance
      gene from the donor E. gallinarum was performed in a successful conjugation
      experiment in vitro, using E. faecium GE-1 and E. faecalis JH22 as receptors.
      This is the first report of the detection of a vanA determinant naturally
      acquired by E. gallinarum in Brazil, indicating the importance of characterizing
      VRE by both phenotype and genotype methods.

PMID- 15517084
TI  - c-erbB-2 expression and nuclear pleomorphism in canine mammary tumors.
AB  - The objective of the present investigation was to study the expression of c-erbB
      2 and MIB-1 and try to associate them with morphological features of the cell
      such as nuclear pleomorphism, mitotic count and histological grade in a series of
      70 canine mammary gland tumors, 22 of them benign and 48 malignant. Tumors were
      collected at the Veterinary Hospital of UFMG (Brazil) and the Veterinary Faculty
      of Porto University (Portugal). c-erbB-2 expression was determined according to
      the guidelines provided by the manufacturer of the HercepTest system and nuclear
      pleomorphism, mitotic count and histological grade according the Elston and Ellis
      grading system. The HercepTest is the FDA-approved in vitro diagnostic test
      marketed by Dako. It is a semi-quantitative immunohistochemical assay used to
      determine overexpression of HER2 protein (human epidermal growth factor receptor)
      in breast cancer tissue. MIB-1 expression was also evaluated in 28 malignant
      tumors. Seventeen (35.4%) of the malignant tumors were positive for c-erbB-2
      expression, which was positively associated with nuclear pleomorphism (P <
      0.0001), histological grade (P = 0.0017) and mitotic count (P < 0.05). Nuclear
      pleomorphism also showed a positive association with MIB-1 index (P < 0.0001).
      These results suggest that some of the biological and morphological
      characteristics of the tumor are associated in canine mammary gland tumors, as
      also reported for human breast cancer. It was also possible to show that the
      immunoexpression of c-erbB-2 can be a factor in mammary carcinogenesis. This fact
      opens the possibility of using anti-c-erbB-2 antibodies in the treatment of
      canine mammary tumors.

PMID- 15517085
TI  - Lack of evidence for mutations or deletions in the CDKN2A/p16 and CDKN2B/p15
      genes of Brazilian neuroblastoma patients.
AB  - Neuroblastoma, the most common extracranial tumor in childhood, has a wide
      spectrum of clinical and biological features. The loss of heterozygosity within
      the 9p21 region has been reported as a prognostic factor. Two tumor suppressor
      genes located in this region, the CDKN2B/p15 and CDKN2A/p16 (cyclin-dependent
      kinase inhibitors 2B and 2A, respectively) genes, play a critical role in cell
      cycle progression and are considered to be targets for tumor inactivation. We
      analyzed CDKN2B/p15 and CDKN2A/p16 gene alterations in 11 patients, who ranged in
      age from 4 months to 13 years (male/female ratio was 1.2:1). The most frequent
      stage of the tumor was stage IV (50%), followed by stages II and III (20%) and
      stage I (10%). The samples were submitted to the multiplex PCR technique for
      homozygous deletion analysis and to single-strand conformation polymorphism and
      nucleotide sequencing for mutation analysis. All exons of both genes were
      analyzed, but no deletion was detected. One sample exhibited shift mobility
      specific for exon 2 in the CDKN2B/p15 gene, not confirmed by DNA sequencing.
      Homozygous deletions and mutations are not involved in the inactivation mechanism
      of the CDKN2B/p15 and CDKN2A/p16 genes in neuroblastoma; however, these two
      abnormalities do not exclude other inactivation pathways. Recent evidence has
      shown that the expression of these genes is altered in this disease. Therefore,
      other mechanisms of inactivation, such as methylation of promoter region and
      unproperly function of proteins, may be considered in order to estimate the real
      contribution of these genes to neuroblastoma genesis or disease progression.

PMID- 15517086
TI  - Diagnosis, staging and treatment of hepatocellular carcinoma.
AB  - Hepatocellular carcinomas are aggressive tumors with a high dissemination power.
      An early diagnosis of these tumors is of great importance in order to offer the
      possibility of curative treatment. For an early diagnosis, abdominal ultrasound
      and serum alpha-fetoprotein determinations at 6-month intervals are suggested for
      all patients with cirrhosis of the liver, since this disease is considered to be
      the main risk factor for the development of the neoplasia. Helicoidal computed
      tomography, magnetic resonance and/or hepatic arteriography are suggested for
      diagnostic confirmation and tumor staging. The need to obtain a fragment of the
      focal lesion for cytology and/or histology for a diagnosis of hepatocellular
      carcinoma depends on the inability of imaging methods to diagnose the lesion.
      Several classifications are currently available for tumor staging in order to
      determine patient prognosis. All take into consideration not only the stage of
      the tumor but also the degree of hepatocellular dysfunction, which is known to be
      the main factor related to patient survival. Classifications, however, fail to
      correlate treatment with prognosis and cannot suggest the ideal treatment for
      each tumor stage. The Barcelona Classification (BCLC) attempts to correlate tumor
      stage with treatment but requires prospective studies for validation. For single
      tumors smaller than 5 cm or up to three nodules smaller than 3 cm, surgical
      resection, liver transplantation and percutaneous treatment may offer good anti
      tumoral results, as well as improved patient survival. Embolization or
      chemoembolization are therapeutic alternatives for patients who do not benefit
      from curative therapies.

PMID- 15517087
TI  - Epstein-Barr virus infection and gastric carcinoma in Sao Paulo State, Brazil.
AB  - Epstein-Barr virus (EBV) is a ubiquitous herpesvirus, and most people have
      serological evidence of previous viral infection at adult age. EBV is associated
      with infectious mononucleosis and human cancers, including some lymphomas and
      gastric carcinomas. Although EBV was first reported in lymphoepithelioma-like
      gastric carcinoma, the virus was also found in conventional adenocarcinomas. In
      the present study, 53 gastric carcinomas diagnosed in Sao Paulo State, Brazil,
      were evaluated for EBV infection by non-isotopic in situ hybridization with a
      biotinylated probe (Biotin-AGACACCGTCCTCACCACCC GGGACTTGTA) directed to the viral
      transcript EBER-I, which is actively expressed in EBV latently infected cells.
      EBV infection was found in 6 of 53 (11.32%) gastric carcinomas, mostly from male
      patients (66.7%), with a mean age of 59 years old. Most EBV-positive tumors were
      in gastric antrum. Two EBV-positive tumors (33.3%) were conventional
      adenocarcinomas, whereas four (66.7%) were classified as lymphoepithelioma-like
      carcinomas. EBV infection in gastric carcinomas was reported elsewhere in
      frequencies that range from 5.6% (Korea) up to 18% (Germany). In Brazil, a
      previous work found EBV infection in 4 of 80 (5%) gastric carcinomas, whereas
      another study found 4.7 and 11.2% of EBV-positive gastric carcinomas of
      Brazilians of Japanese origin or not, respectively. In the present study, the
      frequency of EBV-positive gastric carcinomas is similar to that reported in other
      series, and the clinicopathologic characteristics of these EBV-positive tumors
      are in agreement with the data in the literature.

PMID- 15517088
TI  - Social disability of Brazilian mood disorder patients.
AB  - Mood disorders cause many social problems, often involving family relationships.
      Few studies are available in the literature comparing patients with bipolar,
      unipolar, dysthymic, and double depressive disorders concerning these aspects. In
      the present study, demographic and disease data were collected using a
      specifically prepared questionnaire. Social adjustment was assessed using the
      Disability Adjustment Scale and family relationships were evaluated using the
      Global Assessment of Relational Functioning Scale. One hundred patients under
      treatment for at least 6 months were evaluated at the Psychiatric Outpatient
      Clinic of the Botucatu School of Medicine, UNESP. Most patients were women (82%)
      more than 50 (49%) years old with at least two years of follow-up, with little
      schooling (62% had less than 4 years), and of low socioeconomic level. Logistic
      regression analysis showed that a diagnosis of unipolar disorder (P = 0.003, OR =
      0.075, CI = 0.014-0.403) and dysthymia (P = 0.001, OR = 0.040, CI = 0.006-0.275)
      as well as family relationships (P = 0.002, OR = 0.953, CI = 0914-0.992) played a
      significant role in social adjustment. Unipolar and dysthymic patients presented
      better social adjustment than bipolar and double depressive patients (P < 0.001),
      results that were not due to social class. These patients, treated at a teaching
      hospital, may represent the severest mood disorder cases. Evaluations were made
      knowing the diagnosis of the patients, which might also have influenced some of
      the results. Social disabilities among mood disorder patients are very frequent
      and intensive.

PMID- 15517089
TI  - Neuropsychological rehabilitation of memory deficits and activities of daily
      living in patients with Alzheimer's disease: a pilot study.
AB  - Patients with Alzheimer's disease (AD) gradually lose their cognitive competence,
      particularly memory, and the ability to perform daily life tasks.
      Neuropsychological rehabilitation is used to improve cognitive functions by
      facilitating memory performance through the use of external aids and internal
      strategies. The effect of neuropsychological rehabilitation through memory
      training - motor movements, verbal association, and categorization - and
      activities of daily living (ADL) training was tested in a sample of 5 elderly out
      patients (mean age: 77.4 +/- 2.88 years), with mild AD (Mini-Mental State
      Examination score: 22.20 +/- 2.17) and their caregivers. All patients had been
      taking rivastigmine (6-12 mg/day) for at least 3 months before being assigned to
      the rehabilitation sessions, and they continued to take the medication during the
      whole program. Just before and after the 14-week neuropsychological
      rehabilitation program all patients were assessed by interviewers that did not
      participate in the cognitive training, using the Mini-Mental State Examination,
      Montgomery-Alsberg Depression Rating Scale, Hamilton Anxiety Scale, Interview to
      Determine Deterioration in Functioning in Dementia, Functional Test, Memory
      Questionnaire of Daily Living for patient and caregiver, Quality of Life
      Questionnaire for patient and caregiver, and a neuropsychological battery. The
      results showed a statistically significant improvement in ADL measured by
      Functional Test (P = 0.04), and only a small improvement in memory and
      psychiatric symptoms. Our results support the view that weekly stimulation of
      memory and training of ADL is believed to be of great value in AD treatment, not
      only delaying the progress of the disease, but also improving some cognitive
      functions and ADL, even though AD is a progressively degenerative disease.

PMID- 15517090
TI  - Normative data for the Brazilian population in the Boston Diagnostic Aphasia
      Examination: influence of schooling.
AB  - In Neurolinguistics, the use of diagnostic tests developed in other countries can
      create difficulties in the interpretation of results due to cultural, demographic
      and linguistic differences. In a country such as Brazil, with great social
      contrasts, schooling exerts a powerful influence on the abilities of normal
      individuals. The objective of the present study was to identify the influence of
      schooling on the performance of normal Brazilian individuals in the Boston
      Diagnostic Aphasia Examination (BDAE), in order to obtain reference values for
      the Brazilian population. We studied 107 normal subjects ranging in age from 15
      to 84 years (mean +/- SD = 47.2 +/- 17.6 years), with educational level ranging
      from 1 to 24 years (9.9 +/- 4.8 years). Subjects were compared for scores
      obtained in the 28 subtests of the BDAE after being divided into groups according
      to age (15 to 30, N = 24, 31 to 50, N = 33 and 51 years or more, N = 50) and
      education (1 to 4, N = 26, 5 to 8, N = 17 and 9 years or more, N = 61). Subjects
      with 4 years or less of education performed poorer in Word Discrimination, Visual
      Confrontation Naming, Reading of Sentences and Paragraphs, and Primer-Level
      Dictation (P < 0.05). When breakdown by schooling was 8 years or less, subjects
      performed poorer in all subtests (P < 0.05), except Responsive Naming, Word
      Recognition and Word-Picture Matching. The elderly performed poorer (P < 0.05) in
      Complex Ideational Material, Visual Confrontation Naming, Comprehension of Oral
      Spelling, Written Confrontation Naming, and Sentences to Dictation. We present
      the reference values for the cut-off scores according to educational level.

PMID- 15517091
TI  - The reliability of the Brazilian version of the Composite International
      Diagnostic Interview (CIDI 2.1).
AB  - The objective of the present study was to determine the reliability of the
      Brazilian version of the Composite International Diagnostic Interview 2.1 (CIDI
      2.1) in clinical psychiatry. The CIDI 2.1 was translated into Portuguese using
      WHO guidelines and reliability was studied using the inter-rater reliability
      method. The study sample consisted of 186 subjects from psychiatric hospitals and
      clinics, primary care centers and community services. The interviewers consisted
      of a group of 13 lay and three non-lay interviewers submitted to the CIDI
      training. The average interview time was 2 h and 30 min. General reliability
      ranged from kappa 0.50 to 1. For lifetime diagnoses the reliability ranged from
      kappa 0.77 (Bipolar Affective Disorder) to 1 (Substance-Related Disorder, Alcohol
      Related Disorder, Eating Disorders). Previous year reliability ranged from kappa
      0.66 (Obsessive-Compulsive Disorder) to 1 (Dissociative Disorders, Maniac
      Disorders, Eating Disorders). The poorest reliability rate was found for Mild
      Depressive Episode (kappa = 0.50) during the previous year. Training proved to be
      a fundamental factor for maintaining good reliability. Technical knowledge of the
      questionnaire compensated for the lack of psychiatric knowledge of the lay
      personnel. Inter-rater reliability was good to excellent for persons in
      psychiatric practice.

PMID- 15517092
TI  - Estradiol and testosterone concentrations in follicular fluid as criteria to
      discriminate between mature and immature oocytes.
AB  - The objective of the present study was to examine the association between
      follicular fluid (FF) steroid concentration and oocyte maturity and fertilization
      rates. Seventeen infertile patients were submitted to ovulation induction with
      urinary human follicle-stimulating hormone, human menopausal gonadotropin and
      human chorionic gonadotropin (hCG). A total of 107 follicles were aspirated after
      hCG administration, the oocytes were analyzed for maturity and 81 of them were
      incubated and inseminated in vitro. Progesterone, estradiol (E2), estrone,
      androstenedione, and testosterone were measured in the FF. E2 and testosterone
      levels were significantly higher in FF containing immature oocytes (median =
      618.2 and 16 ng/ml, respectively) than in FF containing mature oocytes (median =
      368 and 5.7 ng/ml, respectively; P < 0.05). Progesterone, androstenedione and
      estrone levels were not significantly different between mature and immature
      oocytes. The application of the receiver-operating characteristic curve
      statistical approach to determine the best cut-off point for the discrimination
      between mature and immature oocytes indicated levels of 505.8 ng/ml for E2 (81.0%
      sensitivity and 81.8% specificity) and of 10.4 ng/ml for testosterone (90.9%
      sensitivity and 82.4% specificity). Follicular diameter was associated negatively
      with E2 and testosterone levels in FF. There was a significant increase in
      progesterone/testosterone, progesterone/E2 and E2/testosterone ratios in FF
      containing mature oocytes, suggesting a reduction in conversion of C21 to C19,
      but not in aromatase activity. The overall fertility rate was 61% but there was
      no correlation between the steroid levels or their ratios and the fertilization
      rates. E2 and testosterone levels in FF may be used as a predictive parameter of
      oocyte maturity, but not for the in vitro fertilization rate.

PMID- 15517093
TI  - Hereditary motor and autonomic neuronopathy 1 maps to chromosome 20q13.2-13.3.
AB  - The spinal muscular atrophies (SMA) or hereditary motor neuronopathies result
      from the continuous degeneration and death of spinal cord lower motor neurons,
      leading to progressive muscular weakness and atrophy. We describe a large
      Brazilian family exhibiting an extremely rare, late-onset, dominant, proximal,
      and progressive SMA accompanied by very unusual manifestations, such as an
      abnormal sweating pattern, and gastrointestinal and sexual dysfunctions,
      suggesting concomitant involvement of the autonomic nervous system. We propose a
      new disease category for this disorder, 'hereditary motor and autonomic
      neuronopathy', and attribute the term, 'survival of motor and autonomic neurons
      1' (SMAN1) to the respective locus that was mapped to a 14.5 cM region on
      chromosome 20q13.2-13.3 by genetic linkage analysis and haplotype studies using
      microsatellite polymorphic markers. This locus lies between markers D20S120 and
      D20S173 showing a maximum LOD score of 4.6 at D20S171, defining a region with 33
      known genes, including several potential candidates. Identifying the SMAN1 gene
      should not only improve our understanding of the molecular mechanisms underlying
      lower motor neuron diseases but also help to clarify the relationship between
      motor and autonomic neurons.

PMID- 15517094
TI  - A case follow-up report: possible health benefits of extra virgin olive oil.
AB  - In the course of a case study, a number of issues regarding the dynamics of blood
      cholesterol levels were identified. In this follow-up report, these issues are
      addressed. For example, issues of past behaviour and seasonality, intraindividual
      variation, and nonstationarity appear important over and above controllable
      variables such as diet and exercise. In this report, we conceptualise an
      alternative protective role for the dynamic blood cholesterol levels in a healthy
      population. Furthermore, regular consumption of extra virgin olive oil as
      produced in this case study may interact with the dynamics of cholesterol
      naturally. We recommend that future studies of this kind ought to include a time
      series of blood cholesterol based on daily measurements or intervals much shorter
      than the bimonthly measurements and to include measures of overall well being as
      covariates.

PMID- 15517095
TI  - The life mission theory VI. A theory for the human character: healing with
      holistic medicine through recovery of character and purpose of life.
AB  - The human character can be understood as an extension of the life mission or
      purpose of life, and explained as the primary tool of a person to impact others
      and express the purpose of life. Repression of the human character makes it
      impossible for a person to realize his personal mission in life and, therefore,
      is one of the primary causes of self-repression resulting in poor quality of
      life, health, and ability. From Hippocrates to Hahnemann, repression of physical,
      mental, and spiritual character can be seen as the prime cause of disease, while
      recovery of character has been the primary intention of the treatment. In this
      paper, human character is explained as an intersubjective aspect of consciousness
      with the ability to influence the consciousness of another person directly. To
      understand consciousness, we reintroduce the seven-ray theory of consciousness
      explaining consciousness in accordance with a fractal ontology with a bifurcation
      number of seven (the numbers four to ten work almost as well). A case report on a
      female, aged 35 years, with severe hormonal disturbances, diagnosed with
      extremely early menopause, is presented and treated according to the theory of
      holistic existential healing (the holistic process theory of healing). After
      recovery of her character and purpose of life, her quality of life dramatically
      improved and hormonal status normalized. We believe that the recovery of human
      character and purpose of life was the central intention of Hippocrates and thus
      the original essence of western medicine. Interestingly, there are strong
      parallels to the peyote medicine of the Native Americans, the African Sangomas,
      the Australian Aboriginal healers, and the old Nordic medicine. The recovery of
      human character was also the intention of Hahnemann''s homeopathy. We believe
      that we are at the core of consciousness-based medicine, as recovery of purpose
      of life and human character has been practiced as medicine in most human cultures
      throughout time. We believe that such recovery can help some (motivated) patients
      to survive, even with severe disease.

PMID- 15517096
TI  - Incidental discovery of emphysematous cystitis with rapid resolution in a patient
      presenting with acute pancreatitis.

PMID- 15517098
TI  - Induction of cell activation processes by low frequency electromagnetic fields.
AB  - Electromagnetic fields (EMF) such as those from electric power transmission and
      distribution lines (50/60 Hz) have been associated with increased risk of
      childhood leukemia, cancer of the nervous system, and lymphomas. Several in vitro
      studies on EMF effects were performed to clarify the existing controversies,
      define the risks, and determine the possible mechanisms of adverse effects. In
      some of these reports, the effects were related to other mechanisms of
      carcinogenesis. Modification in cell proliferation was observed after EMF
      exposure and a few reports on cytotoxic effects have also been published. This
      limited review gives an overview of the current results of scientific research
      regarding in vitro studies on the effects of power line frequency EMF, but also
      cell biological mechanisms and their potential involvement in genotoxicity and
      cytotoxicity are discussed. Cell cycle control and signal transduction processes
      are included to elucidate the biochemical background of possible interactions.
      Exposure to EMF has been also linked to the incidence of leukemia and other
      tumors in some epidemiological studies and is considered as "possibly
      carcinogenic to humans", but there is no well-established biological mechanism
      that explains such a relation. Furthermore, EMF is also shown as a stimulus for
      immune relevant cells (e.g., macrophages) to release free radicals. It is known
      that chronic activation of macrophages is associated with the onset of
      phagocytosis and leads to increased formation of reactive oxygen species, which
      themselves may cause DNA damage and are suggested to lead to carcinogenesis. To
      demonstrate a possible interaction between EMF and cellular systems, we present a
      mechanistic model describing cell activation as a major importance for cellular
      response.

PMID- 15517099
TI  - Electromagnetic fields and human endocrine system.
AB  - Extremely low frequency electromagnetic fields (ELF EMF) are commonly present in
      daily life all over the world. Moreover, EMF are used in the physiotherapy of
      many diseases because of their beneficial effects. There is widespread public
      concern that EMF may have potential consequences for human health. Although
      experimental animal studies indicate that EMF may influence secretion of some
      hormones, the data on the effects of EMF on human endocrine system are scarce.
      Most of the results concentrate on influence of EMF on secretion of melatonin. In
      this review, the data on the influence of EMF on human endocrine system are
      briefly presented and discussed.

PMID- 15517100
TI  - Effects of 2.45-GHz electromagnetic fields with a wide range of SARs on
      micronucleus formation in CHO-K1 cells.
AB  - There has been considerable discussion about the influence of high-frequency
      electromagnetic fields (HFEMF) on the human body. In particular, HFEMF used for
      mobile phones may be of great concern for human health. In order to investigate
      the properties of HFEMF, we have examined the effects of 2.45-GHz EMF on
      micronucleus (MN) formation in Chinese hamster ovary (CHO)-K1 cells. MN formation
      is induced by chromosomal breakage or inhibition of spindles during cell division
      and leads to cell damage. We also examined the influence of heat on MN formation,
      since HFEMF exposure causes a rise in temperature. CHO-K1 cells were exposed to
      HFEMF for 2 h at average specific absorption rates (SARs) of 5, 10, 20, 50, 100,
      and 200 W/kg, and the effects on these cells were compared with those in sham
      exposed control cells. The cells were also treated with bleomycin alone as a
      positive control or with combined treatment of HFEMF exposure and bleomycin. Heat
      treatment was performed at temperatures of 37, 38, 39, 40, 41, and 42 degrees C.
      The MN frequency in cells exposed to HFEMF at a SAR of lower than 50 W/kg did not
      differ from the sham-exposed controls, while those at SARs of 100 and 200 W/kg
      were significantly higher when compared with the sham-exposed controls. There was
      no apparent combined effect of HFEMF exposure and bleomycin treatment. On heat
      treatment at temperatures from 38-42 degrees C, the MN frequency increased in a
      temperature-dependent manner. We also showed that an increase in SAR causes a
      rise in temperature and this may be connected to the increase in MN formation
      generated by exposure to HFEMF.

PMID- 15517101
TI  - Influence of 50-Hz electromagnetic field on anurian (Xenopus laevis)
      metamorphosis.
AB  - In this study, we show the effect of a 1-mT magnetic field AC at 50 Hz on Xenopus
      laevis tadpole populations. In the course of a 65-day exposure to the field,
      tadpole survival showed a small, but significant, decrease (p < 0.0004), together
      with a striking parallel 6-day shift in tadpole maturation frequency and a
      significant impairment of their metamorphosis. Particularly, metamorphosis was
      successful for 85% of individuals in the unirradiated tadpole population and for
      45% of individuals in the irradiated tadpole population, respectively.

PMID- 15517102
TI  - Effect of 910-MHz electromagnetic field on rat bone marrow.
AB  - Aiming to investigate the possibility of electromagnetic fields (EMF) developed
      by nonionizing radiation to be a noxious agent capable of inducing genotoxicity
      to humans, in the current study we have investigated the effect of 910-MHz EMF in
      rat bone marrow. Rats were exposed daily for 2 h over a period of 30 consecutive
      days. Studying bone marrow smears from EMF-exposed and sham-exposed animals, we
      observed an almost threefold increase of micronuclei (MN) in polychromatic
      erythrocytes (PCEs) after EMF exposure. An induction of MN was also observed in
      polymorphonuclear cells. The induction of MN in female rats was less than that in
      male rats. The results indicate that 910-MHz EMF could be considered as a noxious
      agent capable of producing genotoxic effects.

PMID- 15517103
TI  - The biological effect of extremely low frequency electromagnetic fields and
      vibrations on barley seed hydration and germination.
AB  - The changes of wet and dry weights and germination of barley seed in different
      periods of its swelling in nontreated (control), extremely low frequency
      electromagnetic fields (ELF EMF) )-treated, and extremely low frequency
      vibrations (ELFV)-treated cold (4 degrees C) and warm (20 degrees C) distilled
      water (DW) were studied. The metabolic-dependent seed hydration, dry weight
      dissolving, germination, and water binding in seed were modulated by preliminary
      EMF- and ELFV-treated DW. Frequency "windows" for the effect of EMF and ELFV on
      seed hydration, solubility, water binding in seed, and germination were
      discovered. These "windows" were different for EMF and ELFV, as well as in
      various phases of seed swelling. It is suggested that EMF-induced water structure
      modification has a different biological effect on the process of seed hydration,
      solubility, water binding in seed, and germination compared to ELFV.

PMID- 15517104
TI  - The effects of 910-MHz electromagnetic field on rat cranial arachnoid and dura
      mater collagen. The axial periodicity of collagen fibrils.
AB  - The axial periodicity of rat arachnoid and dura mater collagen fibrils exposed to
      910 MHz for 2 h/day for 30 consecutive days was measured by means of image
      analysis of electron-optical data. Such measurements were compared with those
      from sham-exposed animals. These measurements reveal that on exposure, the
      intermolecular interactions during collagen fibril assembly are affected.

PMID- 15517105
TI  - Alteration of tight and adherens junctions on 50-Hz magnetic field exposure in
      Madin Darby canine kidney (MDCK) cells.
AB  - Adherens (AJ) and tight junctions (TJ), as integrated parts of the junctional
      complex, are multifunctional specialized regions of the cell membrane in
      epithelial cells. They are responsible for cell-to-cell interactions and also
      have great importance in cellular signaling processes including Wnt protein
      mediated signals. As electromagnetic field (EMF) exposure is known to cause
      alterations in the function as well as supramolecular organization of different
      cell contacts, our goal was to investigate the effect of 50-Hz magnetic field
      (MF) exposures on the subcellular distribution of some representative structural
      proteins (occludin, beta-catenin, and cadherin) found in AJ and TJ. Additionally,
      cellular beta-catenin content was also quantified by Western blot analysis. 50-Hz
      MF exposures seemed to increase the staining intensity (amount) of occludin,
      cadherins, and beta-catenin in the junctional area of MDCK cells, while Western
      blot data indicated the quantity of beta-catenin was found significantly
      decreased at both time points after EM exposures. Our results demonstrate that MF
      are able to modify the distribution of TJ and AJ structural proteins, tending to
      stabilize these cell contacts. The quantitative changes of beta-catenin suggest a
      causative relationship between MF effects on the cell junctional complex and the
      Wnt signaling pathway.

PMID- 15517106
TI  - Effects of whole-body 50-Hz magnetic field exposure on mouse Leydig cells.
AB  - The main goal of this study was to evaluate the possible effect of whole-body
      magnetic field (MF) exposure on the steroidogenic capacity of Leydig cells in
      vitro. In four separate experiments, male CFLP mice were exposed to sinusoidal 50
      Hz, 100-microT MF. The duration of exposure was 23.5 h/day over a period of 14
      days. At the end of the exposure, interstitial (Leydig) cells were isolated from
      the testicles of the sham-exposed and exposed animals. The cells were cultured
      for 48 h in the presence or absence of 1, 10, or 100 mIU/ml human chorionic
      gonadotropin (hCG). The luteinizing hormone (LH) analog hCG was used to check the
      testosterone (T) response of the sham-exposed controls and to evaluate the
      possible effect of the whole-body MF exposure on the steroidogenic capacity of
      Leydig cells in vitro. Testosterone content of the culture media and blood sera
      was measured by radioimmunoassay (RIA). In the cultures obtained from MF-exposed
      animals, the hCG-stimulated T response was significantly higher (p < 0.01)
      compared with the sham-exposed controls, while the basal T production of cells
      and the level of serum T remained unaltered. No MF exposure-related
      histopathological alterations were found in testicles, epididymes, adrenals,
      prostates, and pituitary glands. The MF exposure did not affect the animal growth
      rate and the observed hematologic and serum chemical variables. Our results
      indicate a presumably direct effect of whole-body MF exposure on the hCG
      stimulated steroidogenic response of mouse Leydig cells.

PMID- 15517107
TI  - The effect on rat thymocytes of the simultaneous in vivo exposure to 50-Hz
      electric and magnetic field and to continuous light.
AB  - Thymus plays an important role in the immune system and can be modulated by
      numerous environmental factors, including electromagnetic fields (EMF). The
      present study has been undertaken with the aim to investigate the role of long
      term exposure to extremely low frequency electric and magnetic fields (ELF-EMF)
      on thymocytes of rats housed in a regular dark/light cycle or under continuous
      light. Male Sprague-Dawley rats, 2 months old, were exposed or sham exposed for 8
      months to 50-Hz sinusoidal EMF at two levels of field strength (1 kV/m, 5 microT
      and 5 kV/m, 100 microT, respectively). Thymus from adult animals exhibits signs
      of gradual atrophy mainly due to collagen deposition and fat substitution. This
      physiological involution may be accelerated by continuous light exposure that
      induces a massive death of thymocytes. The concurrent exposure to continuous
      light and to ELF-EMF did not change significantly the rate of mitoses compared to
      sham-exposed rats, whereas the amount of cell death was significantly increased,
      also in comparison with animals exposed to EMF in a 12-h dark-light cycle. In
      conclusion, long-term exposure to ELF-EMF, in animals housed under continuous
      light, may reinforce the alterations due to a photic stress, suggesting that, in
      vivo, stress and ELF-EMF exposure can act in synergy determining a more rapid
      involution of the thymus and might be responsible for an increased susceptibility
      to the potentially hazardous effects of ELF-EMF.

PMID- 15517108
TI  - Development of a reliable and low-cost system for the study of EMF biological
      effects.

PMID- 15517112
TI  - [An unexpected difficult intubation. Bonfils rigid fiberscope].
AB  - A solution to managing intubation difficulties during anaesthesia induction is
      described in this article. After two attempts at laryngoscopy had failed,
      endotracheal intubation was achieved by the combined use of a laryngoscope and
      the Bonfils rigid fiberscope. The successful technique involved two
      anaesthesiologists, one who displaced the patient's tongue to the left ventral
      part of the mouth with a laryngoscope and cleared the airway by suctioning, and
      one who accomplished the intubation using the Bonfils rigid fiberscope by
      following the blade of the laryngoscope to the larynx. After securing a good view
      of the vocal cords, the tube was successfully inserted into the trachea. The
      entire procedure of intubation was accomplished within 20 s.

PMID- 15517111
TI  - [Analgesia and sedation in intensive care medicine].
AB  - Sedation and analgesia are relevant aspects for the adequate treatment of
      patients in an intensive care unit. Recent drug developments and new strategies
      for ventilation provide improved sedation management allowing better adaptation
      to the clinical background and individual needs of the patient. This article
      provides an overview on the application of different substance groups. Focus is
      placed on newly developed pharmaceuticals such as dexmedetomidine. Another aspect
      is scoring system-related and EEG-based monitoring of depth of sedation. Modern
      concepts of analgesia and sedation for ICU patients have been developed based on
      the interaction of different parameters such as adaptive sedation and analgesia
      management (ASAM).

PMID- 15517113
TI  - [Patients' needs and expectations regarding anaesthesia. A survey on the pre
      anaesthetic visit of patients and anaesthesiologists].
AB  - BACKGROUND: This prospective survey aimed at elucidating the patients'
      expectations and needs regarding the pre-anaesthetic visit and the forthcoming
      anaesthesia. The same questionnaire was answered by both patients and
      anaesthesiologists. METHODS: A total of 200 ASA I-III patients were interviewed
      prior to the preoperative anaesthetic visit. The questionnaire consisted of the
      topics preoperative affective situation, information and self-estimation of
      anaesthesia knowledge, expectations regarding the pre-anaesthetic
      visit/anaesthesia and extent of information concerning the perioperative course
      including risk and possible complications. The same questionnaire was presented
      to 35 certified anaesthesiologists with the request to estimate the patients'
      answers. Answers were rated using a Likert-scale, a comparison of patients' and
      anaesthesiologists' replies was performed. RESULTS: For all 5 topics considerable
      differences between patients' answers and anaesthesiologists' rating were found
      (e.g. for the assessment of the affective situation, the relevance of family
      physicians as information source, the desired anaesthetic technique or the extent
      of anaesthesia-related risk information). No differences were observed for the
      importance of an anaesthesiologist as information source and fear reduction by
      the pre-anaesthetic visit. CONCLUSIONS: Anaesthesiologists tend to misinterpret
      many patients' expectations and attitudes. The results demonstrate the potential
      for quality improvement of the pre-anaesthetic visit.

PMID- 15517114
TI  - [Anastomotic leaks in the upper gastrointestinal tract].
AB  - Anastomotic leaks are still among the most common severe postoperative
      complications and account for the majority of postoperative deaths after
      esophagectomy and gastrectomy. Every disturbance of the normal postoperative
      course should trigger surgeons to consider an underlying anastomotic leak and
      initiate a specific diagnostic workup. This includes direct endoscopic inspection
      of the anastomosis to evaluate the vitality of the anastomosed organs and the
      size of the leak. Adequate external drainage of the leak and prevention of
      further contamination are the primary therapeutic goals. Selection of therapy is
      guided by the available modalities for sufficiently draining the leak and
      avoiding sepsis. The spectrum of therapeutic options ranges from simple opening
      of the neck incision in cervical esophageal anastomoses, interventional placement
      of drains, to endoscopic intervention with closure of the fistula or placement of
      stents, and reoperation with exclusion, diversion, or discontinuity resection.

PMID- 15517115
TI  - [Kausch-Whipple pancreaticoduodenectomy. Technique and results].
AB  - The Kausch-Whipple operation is the standard procedure for resection of
      pancreatic head cancer, distal bile duct cancer, and periampullary cancers. It is
      also used for some cases of chronic pancreatitis. Traditionally, this operation
      is associated with high perioperative morbidity and mortality. The aim of our
      study was to present our current technique for Kausch-Whipple
      pancreaticoduodenectomy and to demonstrate that acceptable perioperative and long
      term outcomes can be achieved by a standardised technique in a high-volume
      centre.

PMID- 15517116
TI  - [Antipruritic therapy with the oral opioid receptor antagonist naltrexone. Open,
      non-placebo controlled administration in 133 patients].
AB  - BACKGROUND AND OBJECTIVES: The perception of pruritus is modified by endogenous
      and exogenous opioids via central opiate receptors and can be suppressed with
      opioid receptor antagonists. The aim of this investigation was to describe the
      efficacy and safety of naltrexone, an orally active opiate antagonist, in the
      treatment of severe, otherwise intractable pruritus of varying origins. PATIENTS:
      A total of 133 patients with pruritus caused by inflammatory skin diseases
      (asteatotic dermatitis, atopic dermatitis, prurigo, and psoriasis vulgaris),
      liver- and renal diseases, cutaneous lymphoma, as well as with pruritus of
      unknown origin were treated with naltrexone (Nemexin) 50 to 150 mg daily.
      RESULTS: A therapeutic response was achieved in 86 of the 133 (64.6%) patients.
      Naltrexone was most effective in prurigo nodularis, cutaneous lymphoma and
      pruritus of unknown origin. Tachyphylaxis occurred in 13% of the patients, but
      appeared late, and could be counterbalanced by raising the dosage. Adverse drug
      effects were restricted to the first two weeks of treatment and included mainly
      neurological (dizziness, headache, fatigue) and gastrointestinal (nausea,
      vomiting, diarrhea) symptoms. CONCLUSIONS: The oral opiate antagonists may well
      be an effective, well-tolerated therapy for intractable pruritus in many
      diseases.

PMID- 15517117
TI  - [Coccidioidomycosis. Two case reports with discussion of current diagnostic and
      therapeutic issues].
AB  - Coccidioidomycosis is a systemic mycosis that is acquired by inhalation. It is
      endemic in desert-like areas of the southwest USA and neighboring regions, but is
      becoming increasingly prevalent in other regions of the world as a result of
      widespread travel. The clinical spectrum is broad, ranging from inapparent
      infections or symptoms of acute respiratory infection with spontaneous recovery
      to various manifestations of disseminated coccidioidomycosis. Since the majority
      of patients with disseminated coccidioidomycosis present with cutaneous
      manifestations, early diagnosis of this potentially life-threatening disease by
      dermatologists is important. Atypical skin changes, pulmonary infiltrates and a
      history of travel to areas where the disease is endemic are indicative of
      coccidioidomycosis. For conclusive diagnosis, identification of the fungus by
      histopathologic examination or culture is desirable. Serological tests can be
      helpful for establishing the diagnosis and monitoring the course of the disease.
      The treatment of choice for cutaneous coccidioidomycosis is currently oral azole
      antifungal agents, such as itraconazole 400 mg daily, continued for 6 months
      after clinical response. Since relapses are frequent after discontinuation of the
      treatment, close clinical, serological and radiological follow-up is required for
      years.

PMID- 15517118
TI  - [Systemic corticoid application in combination with topical mitomycin or
      dexamethasone. Inhibition of wound healing after tympanic membrane perforation].
AB  - BACKGROUND: The purpose of this study was to determine whether systemic
      glucocorticoid application, in combination with topical mitomycin or
      dexamethasone, prolongs the patency of a tympanic membrane perforation. METHOD:
      Bilateral myringotomies were performed on 24 rats. The 48 ears were separated
      into eight groups. Treatment with combined systemic and topical dexamethasone or
      mitomycin differed between these groups. After the first 2 weeks, the animals
      were checked weekly for a total of 12 weeks. RESULTS: A combination of systemic
      and topical dexamethasone delayed tympanic membrane closure after myringotomy.
      Perforation size increased in all tympanic membranes treated with mitomycin plus
      systemic dexamethasone. CONCLUSION: Topical mitomycin plus systemic
      glucocorticoid may lead to a massive malfunction of tympanic membrane healing.

PMID- 15517119
TI  - [Orbital stabilisation with suprabrow myofascial transposition flaps].
AB  - BACKGROUND: Common reasons for orbital defects are midfacial traumas or defects
      following tumor resection within the sinu-orbital region. In these cases,
      reconstruction of the medial or inferior orbital wall often is required. Common
      materials for orbital reconstruction, such as titanium-mesh, are used where
      epithelialisation problems are frequently encountered. METHODS: Three patients
      with extended resection of malignomas of the medial and inferior orbit wall were
      reconstructed with a myofascial transposition flap from the suprabrow region.
      RESULTS: Orbital tumor infiltration was present in 11 of the 54 patients treated
      from 1997 to 2003 for tumors of the nasal region. In three cases, tumor extension
      to the medial and caudal orbital wall required extensive tissue resection,
      including the periorbit. In these cases, we created a new horizontal fascial flap
      from the suprabrow-region which stabilized the bulbus by fixation to the lateral
      maxilla. Follow-up 12 months after surgery showed good epithelialisation of the
      reconstructed region without functional deficits. CONCLUSION: This previously
      undescribed fascial suprabrow-flap constitutes a valuable method in the
      reconstruction of large combined defects of the medial and caudal orbit wall
      profiting particularly from the autologous material used.

PMID- 15517120
TI  - [Cell transplantation for a CSF-fistula. Experience with fibrin glue and
      fibroblasts].
AB  - BACKGROUND: In the present study we investigated the culturing of fibroblasts on
      fibrin glue embedded suture nets, to analyse the possibility of using these
      components in a suture application technique for the closure of a CSF-fistula.
      RESULTS: Placement of centrally perforated dura pieces on fibrin glue coated
      surfaces resulted in cellular migration from the dura borders into the defect,
      resulting in a complete cellular closure of the perforation. Inversion
      microscopic follow-up during culturing and the Alamar blue-essay found strong
      growth stimulation for oral mucosa fibroblasts on fibrin glue coated surfaces by
      insulin and FGF. Three-dimensional fibroblast growth was observed along the
      suture lines in the presence of fibrin glue. CONCLUSIONS: Fibrin glue is an
      attractive extracellular matrix for cellular migration from the dura which is
      suited to fibroblast culturing in suture nets. Our findings support the idea of
      achieving closure of cerebrospinal fluid fistulas by suture application of
      autologous fibroblasts and fibrin/thrombin preparations as a realistic future
      goal.

PMID- 15517121
TI  - [Cavernous hemangioma of the parotid gland in adults].
AB  - Parotid hemangiomas are rare in adults. Whereas both capillary and cavernous
      hemangiomas are seen in children, only cavernous hemangiomas have thus far been
      reported in adults. Clinically, cavernous hemangiomas usually present as slowly
      growing, soft or firm, movable, painless parotid masses. Severe pain and swelling
      can occur, however, depending on the size of the hemangioma or in particular in
      the presence of acute hemorrhage or thrombosis. CT and MRI are the diagnostic
      tools of choice. Prior to surgery, magnetic resonance angiography or intra
      arterial digital subtraction angiography should be performed to investigate the
      vascular supply of the tumor. Surgical excision is the treatment of choice for
      small lesions. Large cavernous hemangiomas usually require superficial or total
      parotidectomy. Especially in the case of extended lesions, the facial nerve may
      be difficult to identify and should be monitored intraoperatively.

PMID- 15517122
TI  - [Treatment of deep vein thrombosis. When to use which substance?].
AB  - Current antithrombotic therapy of deep vein thrombosis (DVT) consists of an
      initial course of heparin, followed by the secondary prevention with oral
      anticoagulation (OAC). Low molecular weight heparin has several advantages over
      unfractionated heparin, however, renal insufficiency has to be observed to avoid
      accumulation. The synthetic pentasaccharide Fondaparinux is a factor Xa
      inhibitor, that will shortly be available for the initial treatment of DVT. Oral
      anticoagulation with vitamin K antagonists (VKA) is highly effective, the
      standard target INR is 2.0-3.0. For a first episode of DVT the duration of OAC
      usually is six months, but has to be adjusted according to the estimated risk for
      recurrence. Because of the narrow therapeutic window of VKA, low molecular weight
      heparins are increasingly being used for secondary prevention in patients with an
      increased risk for bleeding, mostly in 1/2-therapeutic dose. At present, several
      new antithrombotic agents are being studied and may become available shortly for
      DVT treatment.

PMID- 15517123
TI  - [Monoclonal antibody treatment of malignant lymphoma].
AB  - In the last years monoclonal antibodies directed against B-cell associated
      epitopes have enriched our armentarium of therapeutic strategies against
      malignant B-cell lymphoma. Monoclonal antibodies are characterized by a different
      mode of action compared to chemotherapy, thereby opening new avenues in lymphoma
      treatment. These monoclonal antibodies can exert their anti-lymphoma activity
      directly by an intrinsic cytotoxic effect or indirectly as a carrier of cytotoxic
      drugs or radioisotopes. Rituximab, an anti-CD20 monoclonal antibody, was proven
      to be highly active in indolent as well as aggressive lymphoma, in particular
      when combined with chemotherapy. The anti-CD52 antibody alemtuzumab was shown to
      induce remissions in high risk CLL. Furthermore, clinical trials have
      demonstrated promising activity of monoclonal antibodies conjugated to
      radioisotopes such as the (131)iodine anti-CD20 antibody tositumomab or the
      (90)yttrium anti-CD20 antibody ibritumomab tiuxetan.

PMID- 15517124
TI  - [Therapy of inflammatory kidney diseases. More than steroids?].
AB  - The term "inflammatory kidney diseases" characterizes primarily
      immunopathogenetically driven diseases, affecting both kidneys. Bacterial
      infections, or primarily interstitial nephritis, shall not be considered in this
      overview. Classification and terminology of inflammatory kidney diseases follow
      morphological criteria, acuteness of the clinical course, and concomitant organ
      affection. The clinical course and pathology of inflammatory kidney diseases have
      been reviewed extensively in this journal in 1997 and 2002.

PMID- 15517125
TI  - [Are "biologics" in the treatment of rheumatoid arthritis really cost
      effective?].
AB  - Since the biologics have been introduced in clinical rheumatology, the landscape
      for medication of rheumatoid arthritis has changed substantially. A completely
      new family of drugs had to be evaluated for efficacy with regard to its impact on
      amelioration of disease activity but also with regard to long-term side effects
      and costs. This evaluation of effectiveness of biologics belongs to the most
      intensively discussed topics in rheumatology, and at present, only for the
      clinical side adequate answers can be obtained from the published data. On the
      other hand, more long-term observation and prospective studies are needed to be
      able to answer the question of real cost-effectiveness adequately. However, when
      all current data are summarized, the cost for a TNF-inhibitor in regard of one
      quality-adjusted life-year ranges below the internationally recommended critical
      amount of 40,000 euro.

PMID- 15517126
TI  - [Liver transplantation: deciding between need and donor allocation].
AB  - Liver transplantation represents an established therapeutic option for advanced
      liver diseases. The spectrum of indications encompasses infectious, vascular,
      immunological and toxic diseases leading to cirrhosis, in addition to genetic,
      metabolic, developmental and selected neoplastic diseases. On the one hand the
      timing of liver transplantation is determined by the disease specific course
      until decompensation and the disease manifestation involving bile ducts or
      hepatocytes. On the other hand it represents gene therapy of diseases affecting
      the liver, or entities where the genetic defect lies in the liver. In view of the
      shortage of donor organs and an increasing requirement for liver transplantation
      the challenge is to provide an effective and fair waiting list management. Reform
      of allocation criteria has put the focus on urgency. This in turn leads to an
      increase in waiting time for elective transplantations, inclusion of end stage
      diseases and critical patients, higher perioperative costs, problems with the
      matching of organs and the problem of an effective use of organ resources. Fair
      allocation and medical necessity therefore define the challenges surrounding the
      indications for liver transplantation.

PMID- 15517127
TI  - [New therapeutic approaches to COPD].
AB  - Classification of severity of the disease is the basis of the therapeutic concept
      for chronic obstructive lung disease (COPD). Besides pharmacological treatment,
      preventive measures and rehabilitation with training are the main parts of COPD
      therapy. Weaning patients of cigarette smoking is of utmost importance in every
      stage for the course of the disease. Inhalative short acting bronchodilators on
      demand are the basis of treatment in all stages as well as long acting
      bronchodilators from stage II on as continuous medication. Theophyllines are of
      additional importance in higher degrees of the disease. Inhalative steroids are
      indicated in severe stages III or higher, systemic steroids only during
      exacerbations as short course therapy. Oxygen long time treatment, intermittent
      non-invasive ventilation, and operations in some cases are additional therapies.

PMID- 15517128
TI  - Role of the BMK1/ERK5 signaling pathway: lessons from knockout mice.
AB  - Mitogen-activated protein (MAP) kinase cascades play a central role in mediating
      extracellular stimuli-induced intracellular signaling during cell activation. The
      fourth and least studied mammalian MAP kinase pathway, big MAP kinase 1 (BMK1),
      also known as extracellular signal regulated kinase 5 (ERK5), is activated in
      response to growth factors and stress. Activation of this signaling pathway has
      been implicated not only in physiological functions such as cell survival,
      proliferation and differentiation but also in pathological processes such as
      carcinogenesis, cardiac hypertrophy and atherosclerosis. In recent years a series
      of gene-targeted mice lacking components within the BMK1 cascade have been
      generated, which have enabled us to investigate the role of the BMK1 pathway
      within different tissues. Analyses of these knockout mice have led to major
      discoveries in the role of BMK1 signaling in angiogenesis and in cardiac
      development. Moreover, studies using conditional BMK1 knockout mice, which
      circumvent the early embryonic lethality of BMK1 knockouts, have unveiled the
      importance of BMK1 in endothelial survival and maintenance of vascular integrity
      during adulthood. Here we summarize current understanding of the function of
      BMK1, as well as include new data generated from a series of tissue-specific BMK1
      knockout mice in an attempt to dissect the role of the BMK1 pathway in various
      cell types in animals.

PMID- 15517129
TI  - Estrogen receptor genotype modulates myocardial perfusion in young men.
AB  - Most of the effects of estrogens are mediated by estrogen receptors. Vascular
      endothelial cells and smooth muscle cells express estrogen receptor alpha (ESR1)
      in both genders. A long genotype group of a common thymine-adenine (TA)
      dinucleotide repeat polymorphism in the regulatory region of this gene has
      previously been related to coronary artery disease. The present study examined
      whether coronary blood flow is affected by this genotype. A total of 49 healthy
      men were genotyped by PCR and divided into three groups according to median
      number of the ESR1 promoter TA repeat (=19), i.e., in the short allele genotype
      group both alleles were of fewer than 19 repeats whereas in the long allele group
      both alleles were 19 repeats or more. The intermediate group comprised men who
      had one short and one long allele. Myocardial blood flow was measured by positron
      emission tomography using [(15)O]water, performed at rest and during adenosine
      stimulation. Men with long alleles had lower adenosine-stimulated coronary flow
      than those with short alleles and those with one short and one long allele. Our
      results suggest that adenosine-stimulated myocardial perfusion is lower in
      subjects with ESR1 long alleles than the other TA repeat genotypes.

PMID- 15517130
TI  - Site-specific strand bias in gene correction using single-stranded
      oligonucleotides.
AB  - Targeted gene editing mediated by chimeric RNA-DNA oligonucleotides (RDOs) or
      single-stranded oligo-deoxyribonucleotides (ssODNs) has been demonstrated in a
      wide variety of cell types both in vitro and in vivo. In this study we
      investigated the correlation between the polarity of the used oligonucleotides
      and the obtained correction frequency in targeted ssODN-mediated correction of
      two G>A mutations (introduced at positions 659 and 1567, respectively) in an
      episomal beta-galactosidase gene. At position 659 the highest correction
      efficiency was observed using an ssODN complementary to the transcribed strand of
      the target gene. In contrast, at position 1567 the highest correction frequency
      was observed using an ssODN complementary to the nontranscribed strand of the
      target gene. It has been reported that site-specific gene editing mediated by
      ssODNs targeting the nontranscribed strand of the target gene results in a higher
      gene editing frequency, and it has been suggested that steric hindrance or
      displacement of ssODNs by traversing transcription complexes prevents efficient
      targeting of the transcribed strand. However, the results of the present study
      demonstrate that occupancy by transcriptional complexes alone does not dictate
      strand bias in ssODN-mediated gene editing, and that the sequences surrounding
      the targeted nucleotide may profoundly influence strand bias. This finding has
      important implications for the design of optimal ssODNs for targeted editing of a
      given nucleotide sequence.

PMID- 15517132
TI  - [Intra-articular therapy with autologous interleukin-1 receptor antagonist in
      osteoarthritis. Innovation or quackery?].

PMID- 15517131
TI  - -717A>G polymorphism of human C-reactive protein gene associated with coronary
      heart disease in ethnic Han Chinese: the Beijing atherosclerosis study.
AB  - Serum C-reactive protein (CRP) has been strongly implicated in the pathogenesis
      of coronary heart disease (CHD). We report here on the association between gene
      coding for CRP and CHD in the ethnic Han population of China. For this purpose
      two polymorphisms of -717A>G and +2147A>G of the CRP gene were identified by
      direct sequencing of genomic DNA derived from 48 randomly selected patients and
      these were further investigated for associations with CHD in 619 male patients
      and 615 age-matched male normal controls. The frequency of A allele carriers of 
      717A>G polymorphism was significantly higher in patients than in controls by
      univariate analysis. After controlling for other risk factors the association
      between this polymorphism and CHD remained significant by multivariate logistic
      regression analysis. Individuals carrying the -717A allele had an approx. 6.8
      fold higher risk of developing CHD (odds ratio 6.84 compared with those not
      carrying this allele). Haplotype analysis confirmed the results of individual
      polymorphism analyses. However, the resolution of effect size is poor, which may
      be due to the deficiency in sample size of this study. Neither polymorphism was
      observed to have an influence on serum CRP level. Since the frequency difference
      between CHD cases and controls for the -717A allele carriers is only 2.28%, and
      homozygosity for -717G occurs in only 1.78% of subjects, -717 A>G polymorphism is
      not a major determinant of population genetic risk of CHD in the Chinese
      population. The association of this polymorphism with CHD supports the belief
      that carriers of -717A allele of the CRP gene are genetically predisposed to CHD
      in the Chinese Han population, and it remains possible that this polymorphism is
      in disequilibrium with one as yet unidentified functional polymorphism in the
      vicinity.

PMID- 15517133
TI  - Nest excavation in ants: group size effects on the size and structure of
      tunneling networks.
AB  - Collective digging activity was studied in the ant Messor sancta Forel in
      laboratory conditions and with a two dimensional set-up. We analyzed the digging
      dynamics and topology of tunneling networks excavated by groups of workers
      ranging from 50 to 200 individuals over 3 days. In all conditions, the dynamics
      of excavated sand volume were clearly non-linear. Excavation began with an
      exponential growth and after 3 days reached a saturation phase in which activity
      was almost totally stopped. The final volume of sand excavated was positively
      correlated with the number of workers. At the end of the experiments, the two
      dimensional tunneling networks were mapped onto planar graphs where the vertices
      represent small chambers or intersections between tunnels and the edges represent
      tunnels. We found that all the networks belonged to a same topological family and
      exhibited several striking invariants such as the distribution of vertex degree
      that follows a power law. When increasing the number of ants, some changes
      occurred in the network structure, mainly an increase in the number of edges and
      vertices, and the progressive emergence of enlarged and highly connected
      vertices.

PMID- 15517135
TI  - [Koro-like symptoms in a recurrent depressive disorder].
AB  - We report the case of a German male with a major depressive episode who also
      suffered from the terrifying perception that his penis was shrinking. These so
      called koro-like symptoms (KLS) had also been present in earlier depressive
      episodes and subsided in the symptom-free interval of the recurrent depressive
      disorder. Under sufficient antidepressant medication with venlafaxine and lithium
      not only KLS but also the depressive symptoms remitted. The course of illness
      provides further evidence that KLS are not a distinct clinical entity in Western
      countries, but represent a concomitant syndrome that requires treatment of the
      underlying illness.

PMID- 15517136
TI  - [Dyspnea of undetermined origin. Fibrosing alveolitis (FA) in seropositive
      rheumatoid arthritis (RA)].

PMID- 15517134
TI  - Regulation of bone morphogenetic proteins in early embryonic development.
AB  - Bone morphogenetic proteins (BMPs), a large subgroup of the TGF-beta family of
      secreted growth factors, control fundamental events in early embryonic
      development, organogenesis and adult tissue homeostasis. The plethora of dose
      dependent cellular processes regulated by BMP signalling demand a tight
      regulation of BMP activity. Over the last decade, a number of proteins have been
      identified that bind BMPs in the extracellular space and regulate the interaction
      of BMPs with their cognate receptors, including the secreted BMP antagonist
      Chordin. In the early vertebrate embryo, the localized secretion of BMP
      antagonists from the dorsal blastopore lip establishes a functional BMP
      signalling gradient that is required for the determination of the dorsoventral -
      or back to belly - body axis. In particular, inhibition of BMP activity is
      essential for the formation of neural tissue in the development of vertebrate and
      invertebrate embryos. Here we review recent studies that have provided new
      insight into the regulation of BMP signalling in the extracellular space. In
      particular, we discuss the recently identified Twisted gastrulation protein that
      modulates, in concert with metalloproteinases of the Tolloid family, the
      interaction of Chordin with BMP and a family of proteins that share structural
      similarities with Chordin in the respective BMP binding domains. In addition,
      genetic and functional studies in zebrafish and frog provide compelling evidence
      that the secreted protein Sizzled functionally interacts with the Chd-BMP
      pathway, despite being expressed ventrally in the early gastrula-stage embryo.
      These intriguing discoveries may have important implications, not only for our
      current concept of early embryonic patterning, but also for the regulation of BMP
      activity at later developmental stages and tissue homeostasis in the adult.

PMID- 15517137
TI  - [PET/CT imaging in head and neck tumors].
AB  - AIM: To evaluate the usefulness of combined PET/CT examinations for detection of
      malignant tumors and their metastases in head and neck oncology. METHODS: 51
      patients received whole body scans on a dual modality PET/CT system. CT was
      performed without i.v. contrast. The results were compared concerning the
      diagnostic impact of native CT scan on FDG-PET images and the additional value of
      fused imaging. RESULTS: From 153 lesions were 97 classified as malignant on CT
      and 136 on FDG/PET images, as suspicious for malignancy in 33 on CT and 7 on FDG
      PET and as benign in 23 on CT and 10 on FDG-PET. With combined PET/CT all primary
      and recurrent tumors could be found, the detection rate in patients with unknown
      primary tumors was 45%. Compared to PET or CT alone the sensitivity, specifity
      and accuracy could be significantly improved by means of combined PET/CT.
      CONCLUSION: Fused PET/CT imaging with [F18]-FDG and native CT-scanning enables
      accurate diagnosis in 93% of lesions and 90% of patients with head and neck
      oncology.

PMID- 15517138
TI  - [PET/CT in radiotherapy].
AB  - Combining positron emission tomography (PET) and X-ray computed tomography (CT)
      with simultaneous acquisition may improve diagnostic accuracy in oncology.
      Moreover this combination holds considerable promise in radiotherapy. Metabolic
      information may be used in decision making in radiotherapy and in planning target
      volumes. Furthermore early evaluation of treatment efficacy becomes possible. New
      tracers for the assessment of tumour hypoxia or apoptosis in clinical routine are
      currently being developed. These tracers may yield high relevance in
      radiotherapy. Hybrid scanners facilitate patient handling and shorten the
      duration of acquisition. Furthermore fusion accuracy is optimal. Prospective
      studies have to be conducted to show that the new technology improves patient
      care in terms of efficiency and quality.

PMID- 15517140
TI  - [Principles of PET/CT and clinical application].
AB  - Medicine today imposes high demands on diagnosing disease. Techniques should be
      preferably noninvasive, identify the disease at an early stage, and be quick and
      accurate. Frequently, these demands can only be met by employing various
      diagnostic modalities. Consequently, the integration of two imaging modalities,
      such as the combination of PET and CT, increases the quality of coregistration
      and facilitates a timely diagnosis. However, complex imaging procedures require a
      judicious choice of the areas of application. If, for example, both PET and CT
      are indicated then a combined PET/CT exam results in improved diagnosis, whereby
      the actual benefit will depend upon the clinical problem. Typically we expect an
      advantage of 10% with PET/CT compared to separate examinations with CT and PET.
      In addition, PET/CT allows for new indications and applications, which cannot be
      performed satisfactorily with independent examinations and retrospective image
      alignment. One example is the application of PET/CT in radiation therapy
      planning.

PMID- 15517139
TI  - [PET/CT for colorectal and hepatic tumors].
AB  - This contribution presents clinical and technical aspects of combining positron
      emission tomography (PET) and computed tomography (CT) for patients with
      colorectal tumors and characterization of unclear liver foci. In which manner and
      for which patients combined PET/CT is superior to PET or CT alone is also
      discussed. PET/CT can fulfil most prerequisites for imaging in pre- and
      postoperative management of patients with colorectal tumors and best meets the
      desire for optimal imaging procedures. Some of the disadvantages encountered in
      frequently employed CT can be overcome by the combination of PET and CT while
      increasing both sensitivity in detecting lesions and specificity in their
      characterization. Questions regarding treatment response offer an opportunity for
      devising novel study concepts and initiating research on new PET tracers.
      Although few publications are available, we are of the opinion that the
      combination of functional and anatomical imaging provided by PET/CT can improve
      both preoperative management and aftercare. To this end, however, optimum
      cooperation between practitioners of nuclear medicine and radiology is
      imperative.

PMID- 15517142
TI  - [Magnetic resonance imaging in urology. Current techniques].
AB  - Due to low costs and common availability, ultrasonography and computed tomography
      still represent the most common diagnostic tools in uroradiology. However,
      magnetic resonance imaging (MRI) is gaining more and more importance since this
      imaging modality allows for a comprehensive examination of almost the complete
      spectrum of urologic diseases, including congenital malformations. The most
      important advantages of MRI are the free choice of slice orientation, high soft
      tissue contrast and high resolution as well as the lack of radiation. Technical
      progresses in hard and software components have led to a reduction in acquisition
      time, allowing for real-time imaging as well as MR angiography and MR urography
      with a significant reduction in motion artifacts. In addition, contrast enhanced
      MRI represents the imaging modality of choice in patients with reduced renal
      function or known allergy against iodinated contrast agent.

PMID- 15517141
TI  - [PET/CT in lymphoma patients].
AB  - PURPOSE: First results of PET/CT in Hodgkin's disease (HD) and aggressive non
      Hodgkin's lymphoma (NHL) are reported. PATIENTS AND METHODS: From March 2001 to
      August 2004 822 PET/CT were performed at our clinic in lymphoma patients for
      primary staging, restaging after therapy, and diagnosis of recurrence. For
      coregistration non contrast-enhanced low-dose CT were used. RESULTS: Due to the
      exact anatomic localization of (18)F-FDG accumulating lesions equivocal or false
      positive PET findings are avoided. In comparison to contrast enhanced CT, PET/CT
      has a higher sensitivity and specificity in patients with HD and aggressive NHL.
      Integration of PET/CT in treatment planning of radiation therapy optimizes the
      field volume. CONCLUSION: Even in the initial phase of clinical evaluation,
      PET/CT has proven useful in staging and restaging of lymphoma. The exact anatomic
      localization of the PET findings is essential for a precise report, for treatment
      planning of radiation therapy, and for planning surgical biopsy.

PMID- 15517143
TI  - [Computerized supported transrectal ultrasound (C-TRUS) in the diagnosis of
      prostate cancer].
AB  - In the diagnosis of prostate cancer digital rectal examination and transrectal
      ultrasound (TRUS) are the most utilized methods for clinical evaluation. However,
      both methods are not able to differentiate between benign and malignant findings
      with a high amount of certainty. Nevertheless, TRUS is an excellent tool to guide
      biopsies in practically any region of the prostate. The most significant problem
      of visual TRUS interpretation is the lack of specificity, especially being an
      inexperienced user. In order to enhance the diagnostic capabilities of TRUS we
      developed a computerized analysis of the TRUS signal information (C-TRUS/ANNA),
      which was validated by the pathohistologic findings of radical prostatectomies.
      The question was asked: Can C-TRUS detect cancer that has been missed by even
      multiple systematic biopsies? The entrance criteria was prior negative systematic
      random biopsies regardless of number of biopsy sessions or number of individual
      biopsy cores. Five C-TRUS subvisual algorithms were utilized to evaluate the
      information of the ultrasound signal. The most suspicious regions were marked by
      C-TRUS and biopsied by guiding a needle into that specific location. In this
      study 132 with a history of 6-72 negative systematic random biopsies (median: 12
      cores) were evaluated by C-TRUS. The PSA ranged from 3.1-36 ng/ml with a median
      of 9.01 ng/ml. C-TRUS detected in 66 (50%) of these 132 patients cancer by
      targeted biopsies. In thes 66 men the median number of negative biopsy sessions
      were two and a median of 12 biopsy cores had been taken. From the literature, we
      would expect a cancer detection rate in this group with systematic sextant
      biopsies of about 7%. Only five of the detected carcinomas showed a Gleason Score
      (GS) of 5, were as 25 had a GS of 6, 22 a GS of 7 and 15 a GS above 7. The
      results of this prospective clinical trail indicate that C-TRUS is able to
      identify clinically significant cancers that were missed by even multiple
      systematic random biopsies. In addition, the concept of searching for strategies
      that utilize expertise and refinement of imaging modalities is supported rather
      than just elevating the number of random biopsies (i.e. 141 cores in one
      session).

PMID- 15517144
TI  - [Physiology and pathophysiology of erectile dysfunction. A modern contrivance?].
AB  - Notions and hypotheses of the pathophysiologic process in erectile dysfunction-
      its errors and embarrassment--are focused on beginning with Aristotle and
      continued in the Renaissance and the Enlightenment. Only in the middle of the
      nineteenth century was there recognition of the central role of relaxation of the
      trabecular muscles. It took another 100 years until we had a useful treatment
      option at hand.

PMID- 15517145
TI  - Fine genetic mapping of the TuNI locus causing systemic veinal necrosis by turnip
      mosaic virus infection in Arabidopsis thaliana.
AB  - In the pathosystem of turnip mosaic virus (TuMV) and Arabidopsis thaliana, two
      distinct symptoms (mosaic symptom and veinal necrosis) were observed that were
      dependent upon the combination of the TuMV isolate and the Arabidopsis ecotype.
      The Col-0 ecotype developed mosaic symptoms after infection with the TuMV isolate
      Azu while the Ler ecotype developed veinal necrosis after infection with the same
      TuMV isolate. The Ler phenotype is controlled by a single dominant gene TuNI
      (TuMV necrosis inducer) which is located on chromosome 1. The TuNI gene was
      precisely mapped to the ~105 kb interval between the two markers of mXF41 and
      mRF28 by using several types of DNA polymorphism markers. Within this region,
      which included largely duplicated sequences, a total of 19 putative genes were
      predicted and 15 of these were classified into five gene families. The genes
      belonging to the gene families At1g58480 and At1g58602 may function in response
      to infection by pathogens. The gene family At1g58480 encodes lipase-like
      proteins, which might be involved in the induction of defence responses that are
      mediated by salicylic acid. The gene family At1g58602 encodes the CC-NBS-LRR
      (CNL) proteins, which are known to function as one of the plant resistance (R)
      proteins against pathogens. In the present study, the possibility that TuNI might
      function as an R gene was discussed.

PMID- 15517147
TI  - Novel inter-series hybrids in Solanum, section Petota.
AB  - Sexual hybrids between distantly related Solanum species can undergo endosperm
      failure, a post-zygotic barrier in inter-species hybridizations. This barrier is
      explained by the endosperm balance number (EBN) hypothesis, which states that
      parents must have corresponding EBNs for viable seed formation. Tests for inter
      crossability were made involving the Mexican species Solanum pinnatisectum Dunal.
      (series Pinnatisecta, ApiApi, 1EBN), autotetraploids of this species, Solanum
      verrucosum Schlechtd. (series Tuberosa, AA, 2EBN), haploids (2x, 2EBN) of the
      South American S. tuberosum L. (series Tuberosa, A1A1A2A2, 4EBN), and F2 haploid
      species hybrids with South American species (AA, 2EBN) S. berthaultii Hawkes, S.
      sparsipilum (Bitter.) Juz. and Bukasov and S. chacoense Bitter. The development
      of hybrid endosperms was investigated for these combinations by confocal
      microscopy with regard to cell-division timing and tissue collapse. Novel sexual
      diploid (AApi) and triploid (AApiApi) inter-series hybrids were generated from S.
      verrucosum x S. pinnatisectum crosses by using post-pollination applications of
      auxin. F1 embryos were rescued in vitro. The hybrid status of recovered plants
      was verified by microsatellite marker analysis, and the ploidy was determined by
      chromosome counting. The application of phytohormones in inter-ploidy S.
      pinnatisectum x S. tuberosum crosses, however, did not delay endosperm collapse,
      and embryos were not formed. Other diploid, 1EBN species tested in remote
      hybridizations with Group Tuberosum were S. cardiophyllum Lindl., S. trifidum
      Correll, and S. tarnii Hawkes and Hjert., series Pinnatisecta, and S.
      bulbocastanum Dunal., series Bulbocastana. Based on the analysis of post-zygotic
      reproductive barriers among isolated species of section Petota, we propose
      strategies to overcome such incompatibilities.

PMID- 15517148
TI  - Identification of drought-inducible genes and differentially expressed sequence
      tags in barley.
AB  - Drought limits cereal yields in several regions of the world and plant water
      status plays an important role in tolerance to drought. To investigate and
      understand the genetic and physiological basis of drought tolerance in barley,
      differentially expressed sequence tags (dESTs) and candidate genes for the
      drought response were mapped in a population of 167 F8 recombinant inbred lines
      derived from a cross between "Tadmor" (drought tolerant) and "Er/Apm" (adapted
      only to specific dry environments). One hundred sequenced probes from two cDNA
      libraries previously constructed from drought-stressed barley (Hordeum vulgare
      L., var. Tokak) plants and 12 candidate genes were surveyed for polymorphism, and
      33 loci were added to a previously published map. Composite interval mapping was
      used to identify quantitative trait loci (QTL) associated with drought tolerance
      including leaf relative water content, leaf osmotic potential, osmotic potential
      at full turgor, water-soluble carbohydrate concentration, osmotic adjustment, and
      carbon isotope discrimination. A total of 68 QTLs with a limit of detection score
      > or =2.5 were detected for the traits evaluated under two water treatments and
      the two traits calculated from both treatments. The number of QTLs identified for
      each trait varied from one to 12, indicating that the genome contains multiple
      genes affecting different traits. Two candidate genes and ten differentially
      expressed sequences were associated with QTLs for drought tolerance traits.

PMID- 15517149
TI  - Variation in the resistin gene is associated with obesity and insulin-related
      phenotypes in Finnish subjects.
AB  - AIMS/HYPOTHESIS: Resistin is a peptide hormone produced by adipocytes that is
      present at high levels in sera of obese mice and may be involved in glucose
      homeostasis through regulation of insulin sensitivity. Several studies in humans
      have found associations between polymorphisms in the resistin gene and obesity,
      insulin sensitivity and blood pressure. An association between variation in the
      resistin gene and type 2 diabetes has been reported in some, but not all studies.
      The aim of this study was to analyse variants of the resistin gene for
      association with type 2 diabetes and related traits in a Finnish sample. METHODS:
      In 781 cases with type 2 diabetes, 187 spouse controls and 222 elderly controls
      of Finnish origin, we genotyped four previously identified non-coding single
      nucleotide polymorphisms (SNPs): -420C>G from the promoter region, +156C>T and
      +298G>A from intron 2, and +1084G>A from the 3' untranslated region. We then
      tested whether these SNPs were associated with type 2 diabetes and related
      traits. RESULTS: The SNPs were not significantly associated with type 2 diabetes.
      However, SNPs -420C>G, +156C>T and +298G>A and the common haplotype for these
      three markers were associated with increased values of weight-related traits and
      diastolic blood pressure in cases, lower weight in elderly control subjects, and
      lower insulin sensitivity and greater acute insulin response in spouses.
      Furthermore, the +1084G allele was associated with lower HDL cholesterol in both
      cases and controls, higher systolic blood pressure and waist circumference in
      cases, and greater acute insulin response in spouse controls.
      CONCLUSIONS/INTERPRETATION: Our results add to growing evidence that resistin is
      associated with variation in weight, fat distribution and insulin resistance.

PMID- 15517150
TI  - A population-based study of the association between areca nut chewing and type 2
      diabetes mellitus in men (Keelung Community-based Integrated Screening programme
      No. 2).
AB  - AIMS/HYPOTHESIS: The aim of this study was to assess whether the diabetogenicity
      of areca nut (Areca catechu or 'betel-nut'), which has previously been
      demonstrated experimentally in mice, independently contributes to the risk of
      hyperglycaemia or type 2 diabetes in men in Taiwan, where the habit has become
      established relatively recently. METHODS: We used data from a population-based
      cross-sectional survey and a multiple-disease-screening programme that tested for
      hyperglycaemia, type 2 diabetes and risk factors related to type 2 diabetes. Data
      on habitual areca nut chewing were available for 14,816 men. Multiple logistic
      regression models were used to determine whether areca nut chewing was an
      independent risk factor for type 2 diabetes. RESULTS: Compared with non-chewers,
      areca nut chewers had higher age-adjusted prevalence rates for hyperglycaemia
      (11.4% vs 8.7%) and type 2 diabetes (10.3% vs 7.8%). Areca nut chewing
      independently increased the risk of hyperglycaemia (adjusted odds ratio [OR]
      1.19, 95% CI 0.97-1.45) and type 2 diabetes (adjusted OR 1.29, 95% CI 1.04-1.60).
      The independent effects of duration of chewing were dose-dependent for type 2
      diabetes (adjusted OR 1.32 for the duration of 10-19 years and 1.41 for the
      duration of > or =20 years), as were the effects of increased rates of areca nut
      chewing (adjusted OR 1.14 for <10 pieces/day, 1.30 for 10-19 pieces/day and 2.02
      for > or =20 pieces/day); similar findings were noted for hyperglycaemia.
      CONCLUSIONS/INTERPRETATION: The habit of chewing areca nut independently
      contributes to the risk of both hyperglycaemia and type 2 diabetes in Taiwanese
      men. This association is dose-dependent with respect to the duration of areca nut
      use and the quantity of areca nut chewed per day.

PMID- 15517151
TI  - Improved survival of microencapsulated islets during in vitro culture and
      enhanced metabolic function following transplantation.
AB  - AIMS/HYPOTHESIS: The aim of this study was to determine whether a simple alginate
      capsule can prolong islet survival and function during long-term tissue culture.
      We also wanted to observe the ability of these encapsulated islets to restore
      glucose responsiveness to diabetic recipients, along with the quantity of islets
      required to do so. METHODS: We compared the recovery and metabolic function of
      encapsulated canine islets with that of non-encapsulated canine islets following
      1, 2 or 3 weeks of tissue culture. These culture preparations were also
      transplanted into diabetic nude mice and compared for their ability to reverse
      diabetes. Furthermore, short-term cultured encapsulated and non-encapsulated
      islets were transplanted in varying numbers to determine the minimum dose
      required to normalise blood glucose and prolong recipient survival. RESULTS:
      Islet recovery following 1, 2 and 3 weeks of tissue culture was significantly
      higher when islets were encapsulated. When these islets were recovered at 1, 2
      and 3 weeks and transplanted into diabetic nude mice, survival at 100 days was
      100% for all encapsulated groups, versus 66%, 33% and 33% respectively for the
      non-encapsulated islets. Additionally, substantially fewer short-term cultured
      islets were required to normalise blood glucose when the islets were
      encapsulated. Recipients of encapsulated islets also had significantly longer
      survival times than recipients of non-encapsulated preparations.
      CONCLUSIONS/INTERPRETATION: This study demonstrates that encapsulation of islets
      with purified alginate improves islet survival and function in vitro and in vivo.

PMID- 15517152
TI  - A model to estimate the lifetime health outcomes of patients with type 2
      diabetes: the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model
      (UKPDS no. 68).
AB  - AIMS/HYPOTHESIS: The aim of this study was to develop a simulation model for type
      2 diabetes that can be used to estimate the likely occurrence of major diabetes
      related complications over a lifetime, in order to calculate health economic
      outcomes such as quality-adjusted life expectancy. METHODS: Equations for
      forecasting the occurrence of seven diabetes-related complications and death were
      estimated using data on 3642 patients from the United Kingdom Prospective
      Diabetes Study (UKPDS). After examining the internal validity, the UKPDS Outcomes
      Model was used to simulate the mean difference in expected quality-adjusted life
      years between the UKPDS regimens of intensive and conventional blood glucose
      control. RESULTS: The model's forecasts fell within the 95% confidence interval
      for the occurrence of observed events during the UKPDS follow-up period. When the
      model was used to simulate event history over patients' lifetimes, those treated
      with a regimen of conventional glucose control could expect 16.35 undiscounted
      quality-adjusted life years, and those receiving treatment with intensive glucose
      control could expect 16.62 quality-adjusted life years, a difference of 0.27 (95%
      CI: -0.48 to 1.03). CONCLUSIONS/INTERPRETATIONS: The UKPDS Outcomes Model is able
      to simulate event histories that closely match observed outcomes in the UKPDS and
      that can be extrapolated over patients' lifetimes. Its validity in estimating
      outcomes in other groups of patients, however, remains to be evaluated. The model
      allows simulation of a range of long-term outcomes, which should assist in
      informing future economic evaluations of interventions in type 2 diabetes.

PMID- 15517153
TI  - Altered rheology of lymphocytes in the diabetic mouse.
AB  - AIMS/HYPOTHESIS: Clinical complications associated with diabetes may be related
      to altered physical properties of leucocytes. We used micropipette techniques to
      examine leucocyte rheology (specifically lymphocyte rheology) in the non-obese
      diabetic (NOD) mouse model of diabetes mellitus. We hypothesised that diabetes
      affects lymphocyte rheology, and specifically that lymphocyte membranes from
      diabetic mammals have a higher cortical tension than those from non-diabetic
      mammals. METHODS: Lymphocytes were isolated from diabetic and control mice.
      Lymphocyte deformation and activation were assessed with a micropipette
      apparatus. Cellular activation was assessed visually. Projection length into the
      micropipette during aspiration was used to calculate the viscosity of the cell.
      Recovery length following expulsion from the micropipette was used to derive the
      recovery time constant, which is the ratio of cortical tension : viscosity
      (T(o)/mu) for each cell. The cell cortical/surface tension was calculated from
      this ratio. RESULTS: Of 692 control lymphocytes, 29% were spontaneously activated
      compared with 39% of 624 diabetic cells (p<0.06) and 31.5% of 315 non-diabetic
      NOD cells (p=0.14). Viscosity values for diabetic lymphocytes were equivalent to
      those for control cells (1345.12+/-1420.97 Pa.s vs 996.84+/-585.07 Pa.s, p=0.13).
      The average T(o)/micro value for diabetic lymphocytes (35.4+/-16.5x10(-6) cm/s)
      was significantly higher than that for control cells (24.8+/-11.3x10(-6) cm/s,
      p<0.03) and cells from non-diabetic NOD mice (26.3+/-9.0x10(-6) cm/s, p<0.005).
      The mean cortical tension values for diabetic and control cells were 4.7+/
      2.3x10(-4) N/m and 2.8+/-0.7x10(-4) N/m respectively (p<0.003).
      CONCLUSIONS/INTERPRETATION: Lymphocytes from diabetic mice tend to spontaneously
      activate. They have an equivalent cytoplasmic viscosity but a larger recovery
      time constant compared with cells from control mice. The results suggest that
      diabetic lymphocytes are stiffer than control cells.

PMID- 15517154
TI  - The effect of modafinil on counter-regulatory and cognitive responses to
      hypoglycaemia.
AB  - AIMS/HYPOTHESIS: Our hypothesis is that reducing release of the inhibitory
      neurotransmitter gamma-aminobutyric acid (GABA) with modafinil will enhance
      symptomatic and hormonal responses to hypoglycaemia. METHODS: Nine healthy men
      received, in random order, two 100-mg doses of modafinil or placebo, followed by
      an insulin clamp in which plasma glucose was either reduced stepwise to 2.4
      mmol/l or was sustained at euglycaemia (four studies). Catecholamines, symptom
      scores and cognitive function were measured. RESULTS: Modafinil had no effect on
      the measured parameters during euglycaemia. During hypoglycaemia, autonomic
      symptom scores were significantly higher with modafinil (increase at lowest
      plasma glucose concentration 271.3+/-118.9 vs 211.2+/-80.4/40 min, p=0.019), and
      the heart rate response was increased (12,928+/-184 vs 6773+/-148 bpm/140 min,
      p=0.016). Deterioration in performance of two cognitive tasks was reduced: Stroop
      colour-word test (613+/-204 vs 2375+/-161/65 min, p=0.009) and accuracy of a
      simple reaction task (11.3+/-1.8 vs 9.4+/-3.7, p=0.039).
      CONCLUSIONS/INTERPRETATION: We conclude that modafinil improves adrenergic
      sensitivity and some aspects of cognitive function at hypoglycaemia, possibly by
      reducing neuronal central GABA concentrations.

PMID- 15517155
TI  - [In vitro effects of diclofenac and selective cyclooxygenase-2 inhibitors on
      prostaglandin release from inflamed bursa subacromialis tissue in patients with
      subacromial syndrome].
AB  - BACKGROUND: To compare the in vitro effects of selective COX-2 inhibitors (L
      745,337, NS-398 and DFU) and of COX-unspecific diclofenac on release of PGE(2
      )and 6-keto-PGF(1alpha) from inflamed bursa subacromialis tissue (IBST) obtained
      from a total of 35 patients with shoulder impingement syndrome (SIS). PATIENTS
      AND METHODS: Bursal specimens were incubated in the presence of drugs (0.01-1000
      microM) for 20 min and 16 h. RESULTS: After 20 min 10 microM diclofenac
      significantly inhibited formation of PGE(2) and 6-keto-PGF(1alpha), whereas L
      745,337 and NS-398 (10-1000 microM) induced significant inhibition only at
      concentrations > or =100 microM. In contrast to equimolar diclofenac, DFU (0.01
      10 microM) induced no inhibition of bursal PGE(2) release but a dose-dependent,
      although statistically not significant inhibition after 16 h. The inhibitory
      potency of diclofenac (0.01-10 microM) was even more increased during long-term
      incubation showing greater inhibition than DFU at all concentrations studied.
      CONCLUSION: The data suggest that in IBST in SIS in vitro the majority of PG is
      generated via the COX-1 pathway.

PMID- 15517156
TI  - [Lord Byron's club foot. Historical vingette].

PMID- 15517157
TI  - [Results and experiences of conversion of hip arthrodesis ].
AB  - INTRODUCTION: With the predictably good outcome of total hip arthroplasty today
      (THA), hip arthrodesis currently has limited indications. Over the long term,
      however, most patients develop secondary degenerative arthritis in the spine,
      contralateral hip, and ipsilateral knee due to overloading. The deteriorating
      condition of these joints eventually causes the onset of pain, which often
      requires conversion of a fused hip to a THA. The results and experiences of
      conversions of a hip arthrodesis into a THA are reported. INTRODUCTION: Between 1
      January 1985 and 31 December 2001 conversion of a previously performed
      arthrodesis of the hip to THA was carried out in a total of 45 patients; 34
      patients could be followed up after the conversion to THA after a mean of 77.5
      months (min.: 24, max.: 208). The primary indications for the conversion were low
      back pain (n=21) and ipsilateral knee pain (n=13). RESULTS: The mean age at the
      time of THA was 75.3 years (min.: 32, max.: 74). The mean time interval between
      the arthrodesis and the conversion to THA was 30.4 years (min.: 5, max.: 66). Of
      34 hips, 29 (85%) were either pain free or had minimal pain. Complications
      included one persisting sciatic nerve palsy, two superficial infections, two
      periprosthetic fractures, and two heterotopic ossifications IV degrees with one
      recurrence of ankylosis and one marked reduction of motion. Revision arthroplasty
      was performed in four hips. Postoperatively 7 patients showed no limping, 11
      showed a slight limp, and 17 a pronounced limp. Recurrent dislocations occurred
      in one patient. CONCLUSION: We conclude that this operation can lead to
      satisfactory results even after a long duration of the arthrodesis. There is a
      high rate of complications after conversion of a hip arthrodesis to a total hip
      arthroplasty. These issues must be carefully considered and discussed with the
      patient before any conversion procedure.

PMID- 15517158
TI  - [Inflammatory reactions in the wear particle induced and infectious
      periprosthetic membrane of loosened hip- and knee endoprostheses: pathogenetic
      relevance of differentially expressed genes cd9, cd11b, cd18, cd52 and
      pdgfrbeta].
AB  - BACKGROUND: A previous cDNA-microarray analysis described constantly
      differentially expressed genes in wear particle induced and infectious SLIM
      (synovial-like interface membrane). This study aims to validate the cDNA
      microarray data in order to approve differences of the gene expression profiles
      of RNA and proteins. METHODS: Tissue from 16 wear particle induced and 20
      infectious periprosthetic membranes were analyzed by RT-PCR and immunohistology
      with regard to the expression of inflammatoric associated genes. RESULTS: RT-PCR
      showed the genes cd9, cd11b, cd18, cd52 as well as pdgfrbeta in interface
      membranes. In the wear particle induced membrane the immunohistochemical analysis
      showed a significantly weaker gene expression of PDGFRbeta, whereas the
      differential overexpression of CD9, CD11b and CD52 was confirmed. For CD18, there
      was no difference in expression between wear induced and infectious
      periprosthetic tissue. CONCLUSION: Different pathomechanisms, which are reflected
      by different gene expression profiles, might produce different types of
      periprosthetic membranes. By RT-PCR and immunohistochemical analysis the micro
      array data of the genes cd9, cd11b, cd52 and pdgfrbeta could be validated.
      Identifying the gene products of cd9, cd11b and cd52 in blood or tissue may help
      to differentiate between wear induced and infectious loosening.

PMID- 15517159
TI  - Effects of continuous negative extra-abdominal pressure on cardiorespiratory
      function during abdominal hypertension: an experimental study.
AB  - OBJECTIVE: To investigate whether negative extra-abdominal pressure (NEXAP)
      improves respiratory function and induces a blood shift from the intrathoracic
      compartment and to assess whether these effects are influenced by abdominal
      pressure. DESIGN AND SETTING: Prospective, randomized, controlled trial in the
      animal laboratory of a university hospital. SUBJECTS: Eight sedated and paralyzed
      pigs (19.6+/-3.4 kg). INTERVENTIONS: Application of NEXAP (-20 cmH(2)O).
      MEASUREMENTS AND RESULTS: Airway, esophageal, gastric and central venous
      pressures were recorded simultaneously. Intrathoracic blood volume was assessed
      by PiCCO. The effects of NEXAP were assessed with and without abdominal
      hypertension by intraperitoneal insufflation of helium. NEXAP caused a lasting
      drop of gastric (1.97+/-2.26 mmHg) and esophageal (1.21+/-0.67 mmHg) pressures,
      while end-expiratory airway pressure was similar, hence transpulmonary pressure
      increased. Intrathoracic blood volume dropped from 358+/-47 to 314+/-47 ml. The
      fall was associated with a decrease in central venous pressure (R(2)=0.820). When
      peritoneal pressure was raised (24.7+/-5.5 mmHg), the effects were less marked.
      However, the difference between negative pressure around the abdomen and the
      pressure inside the abdomen (effective NEXAP) was correlated with the
      proportional changes in intrathoracic blood volume (R(2)=0.648), being greater
      with more negative effective NEXAP. NEXAP improved chest wall elastance during
      abdominal hypertension (from 0.067+/-0.023 to 0.056+/-0.021 cmH(2)O/ml).
      CONCLUSIONS: NEXAP increases lung volume and causes a shift of blood from the
      intrathoracic compartment. It needs to be tailored against abdominal pressure to
      be effective.

PMID- 15517160
TI  - Severe vagal response after endotoxin administration in humans.
AB  - OBJECTIVE: Endotoxin administration to humans is a common means to study systemic
      inflammation. Worldwide, thousands of volunteers have received endotoxin, and
      adverse events are rarely reported. The aim of this report was to increase
      awareness of specific risks of the intravenous administration of endotoxin to
      human volunteers. DESIGN: Report of four cases who developed severe bradycardia
      or protracted asystole after administration of endotoxin. Interviews with
      investigators at three large centers that conduct normal volunteer endotoxin
      studies. SETTING: Clinical research unit. CASES: Four subjects developed severe
      bradycardia or protracted asystole, approximately 1 h after administration of
      endotoxin. Further analyses revealed that the subjects had a history of vasovagal
      syncope or a positive head-tilt test, indicating increased vagal sensitivity.
      Relative volume depletion associated with fasting overnight may have predisposed
      these subjects to this condition. CONCLUSIONS: These responses are very rare and
      are likely due to the cardioinhibitory Bezold-Jarisch reflex. A thorough
      screening regarding a history of vagal sensitivity and liberal oral or
      intravenous fluid administration prior to and during the endotoxin challenge may
      decrease the risk of these events.

PMID- 15517161
TI  - Dying at the end of your life.

PMID- 15517162
TI  - Withholding and withdrawing life-support therapy in an Emergency Department:
      prospective survey.
AB  - OBJECTIVES: Few studies have focused on decisions to withdraw or withhold life
      support therapies in the emergency department. Our objectives were to identify
      clinical situations where life-support was withheld or withdrawn, the criteria
      used by physicians to justify their decisions, the modalities necessary to
      implement these decisions, patient disposition, and outcome. DESIGN AND SETTING:
      Prospective unicenter survey in an Emergency Department of a tertiary care
      teaching hospital. PATIENTS: All non-trauma patients (n=119) for whom a decision
      to withhold or withdraw life-sustaining treatments was taken between January and
      September 1998. MAIN OUTCOME MEASURES: Choice of criteria justifying the decision
      to withhold or withdraw life-sustaining treatments, time interval from ED
      admission to the decision; type of decision implemented, outcome. RESULTS:
      Fourteen thousand eight hundred and seventy-five non-trauma patients were
      admitted during the study period, 119 were included, mean age 75+/-13 years.
      Resuscitation procedures were instituted for 96 (80%) patients before a
      subsequent decision was taken. Physicians chose on average 6+/-2 items to justify
      their decision; the principal acute medical disorder and futility of care were
      the two criteria most often used. Median time interval to reach the decision was
      187 min. Withdrawal involved 37% of patients and withholding 63% of patients. The
      family was involved in the decision-making process in 72% of patients. The median
      time interval from the decision to death was 16 h (5 min to 140 days).
      CONCLUSION: Withdrawing and withholding life-support therapy involved elderly
      patients with underlying chronic cardiopulmonary disease or metastatic cancer or
      patients with acute non-treatable illness.

PMID- 15517163
TI  - Central venous catheters and cardiac tamponade in preterm infants.
AB  - OBJECTIVE: To determine the incidence of cardiac tamponade related to
      peripherally inserted central catheters in newborns weighing less than 1,500 g
      during the past 8 years and to provide guidelines in order to avoid death due to
      this complication. DESIGN: Retrospective case review. SETTING: Tertiary level
      neonatal intensive care unit. PATIENTS AND PARTICIPANTS: Retrospective study of a
      total of 280 peripherally inserted central catheters positioned in 258 preterm
      newborns. MEASUREMENTS AND RESULTS: Five cardiac tamponades were observed, giving
      an incidence of 1.8%. Data from our cases included clinical presentation and
      outcome, biochemical evaluation of pericardial fluid, days until diagnosis,
      central catheters characteristics, insertion site and tip placement site.
      INTERVENTION: Two of the infants did not respond to resuscitation measures
      including cardiac massage and the administration of epinephrine. Post-mortem
      examination revealed the intrapericardial accumulation of protein and lipid
      alimentation solution. The other three patients were successfully resuscitated by
      timely pericardiocentesis. All five infants had routinely performed serial
      radiographs and cardiac color Doppler ultrasonography that showed correct
      catheter tip placement. CONCLUSIONS: The incidence of cardiac tamponade could be
      reduced by following specific guidelines. The possibility of tamponade must be
      kept in mind during the resuscitation of any preterm infant with a peripherally
      inserted central catheter in place who develops symptoms of shock or sudden
      bradycardia. Our experience shows that even preterm infants with cardiac
      tamponade can be successfully resuscitated by timely pericardiocentesis in most
      cases.

PMID- 15517164
TI  - Severe gastrointestinal complications after 1,515 adult kidney transplantations.
AB  - We studied, retrospectively, the occurrence of severe gastrointestinal (GI)
      complications after kidney transplantation. After 1,515 consecutive adult kidney
      transplantations performed on 1,445 patients during 1990-1999 at our centre, 147
      (10%) severe post-transplantation GI complications were found. Ten percent of the
      complications were fatal. The median follow-up time was 6.2 years. The main
      complications were gastroduodenal ulcers and colon complications. GI malignancy
      developed in 13 patients (0.9%). The complication rate for the first post
      transplantation year was 4.8%. Delayed graft function, high age and polycystic
      kidney disease were risk factors. Five-year patient survival rate was
      significantly lower in patients with a first-year complication than in those with
      later or no GI complications (68% vs 88%). Graft survival with deaths censored
      was the same in both groups. In conclusion, severe GI complications during the
      first post-transplantation year remain a high risk factor also for long-term
      patient survival.

PMID- 15517165
TI  - Renal transplantation in prune-belly syndrome.
AB  - We assess the effect of the prune-belly syndrome (PBS) on renal transplantation
      outcome. Six renal transplantations were performed in five boys affected by PBS
      (median age 5.8+/-2.1 years, median weight 13.6+/-2.4kg). Renal graft survival,
      graft function, lower urinary tract dysfunction, urinary tract infections (UTIs),
      associated complications and patients' survival after 1 and 5 years of follow-up
      were analysed. The rate for 1-5-year graft survival was 66.7% (mean serum
      creatinine 98-103 micromol/l). The surgical treatment of the documented bladder
      obstruction (two patients) and the severe abdominal wall deficit (one patient)
      led to a reduction of UTI: the patients maintained their native urinary tract and
      none received prophylactic antibiotics. The lack of abdominal wall musculature
      led to severe mechanical complication in one patient, but Monfort's abdominal
      wall reconstruction was able to restore the graft's function. The outcome of
      patients with PBS who undergo renal transplantation is good. Before the
      transplant, an accurate assessment of urinary tract anomalies and deficiency of
      the abdominal wall musculature is mandatory, to program the appropriate treatment
      and obtain a good long-term prognosis for the renal graft.

PMID- 15517166
TI  - Pediatric renal transplantation and the dysfunctional bladder.
AB  - We retrospectively reviewed our long-term experience with pediatric renal
      transplantation into a dysfunctional lower urinary tract to evaluate graft
      survival, function, and special urological complications. Between 1967 and March
      2000, a total of 349 renal transplantations were performed in children younger
      than 18 years. Malformations of the lower urinary tract were the reasons for end
      stage renal failure in 66 children (18.6%). The cause of urinary tract disorders
      included: meningomyelocele connected with neuropathic bladder (n = 4
      transplantations); prune belly syndrome (n = 5 transplantations); VATER
      association (n = 2 transplantations); posterior urethral valves (n = 27
      transplantations); and vesico-uretero-renal reflux (n = 28 transplantations). The
      majority of the patients underwent surgical interventions to preserve renal
      function or to prepare renal transplantation. The 1- and 5-year graft survival
      rate was evaluated with special reference to the underlying disease. The 1-year
      graft survival rate in all children with lower urinary tract malformations was
      83.3%, compared with 88% for all children. In those children with vesico-ureteral
      reflux, it was 92.8% and in the children with Vater association and prune belly
      syndrome, it was 85.7%. One graft was lost in the children who had neurogenic
      bladder, so the 1-year graft survival rate was 75%. The worst 1-year graft
      survival rate was obtained for boys who had posterior urethral valves (1-year
      graft survival rate: 74%; 5-year graft survival rate: 62.9%). Concerning the 5
      year graft survival rate, it was 70% for all children with malformations of the
      urinary tract. The best rate was obtained for children with reflux in the native
      kidneys (78.5%), followed by those with VATER association and prune belly
      syndrome. As an additional child with neurogenic bladder lost his graft, the 5
      year graft survival rate was 50%. Pediatric renal transplantation into a
      dysfunctional bladder can be connected with high urological complication rates
      which may contribute to worse graft survival. The 1- and 5-year graft survival
      rate in children with malformations of the lower urinary tract is worse than in
      children without bladder dysfunction. We regarded a striking difference between
      graft survival and the urological disorders which led to renal insufficiency. We
      obtained the worst graft survival rates in children with posterior urethral
      valves which are usually connected with bladder emptying problems and
      dysfunctional voiding. Potential pediatric transplant recipients must be
      classified according to pathophysiological as well as anatomical abnormalities of
      the urinary tract and all urological problems have to be solved prior to
      transplantation. At our center, living donors are favored to plan transplantation
      of these children properly.

PMID- 15517167
TI  - Selective intra-graft apoptosis and down-regulation of lymphocyte bcl-2, iNOs and
      CD95L expression in kidney-pancreas transplanted patients after anti
      Thymoglobulin induction.
AB  - Intra-graft infiltrating cells apoptosis was evaluated in 20 consecutive kidney
      pancreas transplanted (KP) patients without kidney rejection. Two fine-needle
      aspirated biopsy (FNAB) and two peripheral blood lymphocytes (PBL) samples were
      obtained 14 days after transplantation. Immunosuppression was based on anti
      Thymoglobulins (ATG) induction for 7 days and cyclosporine/mofetil mycophenolate
      as maintenance therapy. Ten matched healthy subjects were chosen as controls for
      PBL. Lymphocyte phenotypes and activation markers, apoptotic rate and lymphocyte
      expression of pro/anti-apoptotic molecules were analysed by flow cytometry
      analysis (FACS). Lymphocyte phenotypes and activation markers: higher levels of
      CD8 and CD4DR were evident in the graft (p < 0.05) than in PBL, CD3CD25 in PBL
      were higher in transplanted patients than in controls. Apoptotic rate and
      lymphocyte expression of pro- and anti-apoptotic molecules: a higher expression
      of annexin V, together with reduced lymphocytes CD95L, iNOs and Bcl-2 expression
      (PBL = 97.7+/-1.1% vs FNAB = 81.9+/-15.1%; p < 0.05) were evident in the graft
      than in PBL. In KP patients intra-graft apoptosis and reduced anti-apoptotic
      molecules were evident after ATG induction.

PMID- 15517168
TI  - Aminopyrine breath test in cirrhotic patients awaiting liver transplantation: do
      we really need it ?

PMID- 15517169
TI  - A comparison of traditional open, minimal-incision donor nephrectomy and
      laparoscopic donor nephrectomy.
AB  - Laparoscopic donor nephrectomy (LDN) and minimal-incision donor nephrectomy
      (MILD) are less invasive procedures than the traditional open donor nephrectomy
      approach (ODN). This study compares donor and recipient outcome following those
      three different procedures. Sixty consecutive donor nephrectomies were studied (n
      = 20 in each group). Intra-operative variables, analgesic requirements, donor
      recovery, donor/recipient complications and allograft function were recorded
      prospectively. Operating and first warm ischaemia times were longer for LDN than
      for ODN and MILD (232+/-35 vs 121+/-24 vs 147+/-27 min, P < 0.001; 4+/-1 vs 2+/-2
      vs 2+/-1 min, P < 0.01). Postoperative morphine requirements were significantly
      higher after ODN than after MILD and LDN (182+/-113 vs 86+/-48 vs 71+/-45 mg; P <
      0.0001). There was no episode of delayed graft function in this study. Donors
      returned to work quicker after LDN than after ODN and MILD (6+/-2 vs 11+/-5 vs
      10+/-7; P = 0.055). Donor and recipient complication rates and recipient
      allograft function were comparable. We concluded that MILD and LDN reduce
      postoperative pain and allow a faster recovery without compromising recipient
      outcome.

PMID- 15517170
TI  - Long-term outcome of gastrointestinal complications in renal transplant patients
      treated with mycophenolate mofetil.
AB  - This study examined consequences of gastrointestinal (GI) complications and
      mycophenolate mofetil (MMF) discontinuation on long-term outcomes in patients who
      received MMF at transplantation and had graft function 12 months post
      transplantation. Data were obtained from the United States Renal Data System for
      cadaveric renal transplant recipients between 1995 and 1998. GI complications or
      MMF discontinuation occurred in 27.4% and 17.5% of patients, respectively. MMF
      was discontinued in 21.3% of patients with GI complications and 16.0% of patients
      without (P<0.00001). Four-year graft survival was reduced from 87.1% to 82.3%
      (P=0.091) with MMF discontinuation, to 83.0% (P=0.001) with GI complications, and
      to 70.2% (P<0.0001) with GI complications and MMF discontinuation. While the
      retrospective nature of this work cannot prove causality, which will require
      future prospective studies, both GI complications and MMF withdrawal are
      associated with increased risk of graft loss and may warrant further study in the
      management of transplant recipients.

PMID- 15517171
TI  - Pretransplant screening of sobriety with carbohydrate-deficient transferrin in
      patients suffering from alcoholic cirrhosis.
AB  - Sufficient assessment of potential candidates for orthotopic liver
      transplantation (OLT) is the most important factor for a low alcohol relapse rate
      after transplantation in patients suffering from alcoholic cirrhosis. In the
      current study the efficiency of pretransplant screening with carbohydrate
      deficient transferrin (CDT) was analysed in patients on the waiting list for OLT.
      A prospective study was performed in 44 patients who had undergone OLT for
      alcoholic cirrhosis. All patients had had pretransplant assessment by a
      specialist psychologist and were found to have no problems with alcohol. Pre- and
      post-transplant CDT monitoring was performed. Overall, 790 CDT values were
      measured in the study population. The median observation period was 2.1 months
      before and 41.2 months after transplantation, respectively. In 35 patients (80%)
      pretransplant CDT values were found to be above the reference value, but only one
      patient suffered an alcohol relapse after transplantation. Of the nine patients
      (20%) who demonstrated normal CDT before transplantation, two suffered an alcohol
      relapse after transplantation. CDT is a very useful marker for the monitoring of
      an alcohol relapse in patients following OLT for alcoholic cirrhosis, as has been
      previously indicated. However, CDT does not appear to be useful as a
      pretransplant screening marker for selection of potential transplant candidates
      suffering from alcoholic cirrhosis.

PMID- 15517184
TI  - Mechanical behavior of screws in normal and osteoporotic bone.
AB  - Fracture fixation in severe osteoporotic bone by means of implants that rely on
      screw anchorage is still a clinical problem. So far, a sufficiently accurate
      prediction of the holding capacity of screws as a function of local bone
      morphology has not been obtained. In this study the ultimate pullout loads of
      screws in the epi-, meta-, and diaphyseal regions of human tibiae were correlated
      to the cortical thicknesses and cancellous bone mineral densities at the screw
      axes determined from QCT densitometric data. Stepwise multiple linear regression
      showed that in regions with cortical thicknesses below 1.5 mm, cancellous density
      determined the ultimate pullout load (R2 = 0.85, p < 0.001), while in regions
      with cortices above 1.5 mm, cortical thickness alone significantly influenced the
      holding capacity of a screw (R2 = 0.90, p < 0.001). The findings of this study
      provide a basis for a bone morphology-related pre-operative estimation of the
      holding capacity of screws, which could help to improve their proper application
      in osteoporotic bone.

PMID- 15517185
TI  - Influence of fracture history and bone mineral density testing on the treatment
      of osteoporosis in two non-academic community centers.
AB  - A history of fracture and a low bone mineral density (BMD) are the strongest
      predictors of future osteoporotic fracture. This prospective cohort study
      assessed the impact of these two factors on treatment patterns in women
      undergoing their first BMD testing in a non-academic community setting.
      Successive women seen for first BMD testing at two testing centers completed a
      baseline questionnaire and a mailed 3-month follow-up questionnaire. Patients
      were grouped by history of fracture after age 20 years (present, absent) and by
      BMD result [osteoporosis (OP), osteopenia (OPN), normal BMD]. Thirty percent of
      1144 patients at least 45 years old reported a history of fracture after age 20
      years. They were no more likely than those without a history of fracture to be
      taking calcium (52% of total), vitamin D (31%), estrogen (31%), or a
      bisphosphonate (2%) before BMD testing. The BMD testing revealed OP in 20%, OPN
      in 45%, and normal BMD in 35%. Three months later, the percentages of patients
      taking treatments differed as follows: calcium (66 vs 53% in OP and OPN groups vs
      normal BMD), vitamin D (46 vs 37% in OPN group vs normal BMD), estrogen (25 vs 36
      vs 44% in groups with OP, OPN, and normal BMD), a bisphosphonate (43 vs 11 vs
      1%), and at least one of estrogen or a bisphosphonate (58 vs 43 vs 46%).
      Treatment decisions were influenced by first BMD testing but not significantly by
      a history of fracture. There is a substantial care gap in the treatment of
      patients with OP: either bisphosphonate or estrogen therapy was taken by only 31%
      of patients at least 45 years old and with a history of fracture after age 20
      years before BMD testing and by only 58% of these and who also had OP by BMD.

PMID- 15517186
TI  - Distal humerus fractures in elderly patients: results after open reduction and
      internal fixation.
AB  - PROBLEM: Fractures of the distal humerus are difficult to treat. In elderly
      patients, diminished bone mineral quality and increased trauma-associated joint
      destruction may make stable joint reconstruction even more problematic.
      Furthermore, comorbidities and poor tolerance of joint immobilization might be
      additional factors which influence elbow function negatively. Until now,
      disagreement has existed on how to treat these fractures in elderly patients.
      Recommendations range from conservative treatment to primary total elbow
      replacement. So far, reports in the literature on whether or not open reduction
      and internal fixation in these patients is justified are very rare. AIM OF THE
      STUDY: To analyze fracture patterns, surgical approach, complications, and
      functional results after open reduction and internal fixation in patients of age
      60 years and older. PATIENTS AND METHODS: Retrospective clinical study of two
      university level 1 trauma centers, including 45 patients (median age 73 years;
      range, 61-92 years) with surgically treated distal humerus fractures. Fracture
      patterns were recorded according to their AO classification. All patients were
      treated by open reduction and internal fixation. A clinical and radiological
      follow-up was obtained after a minimum of 24 months following surgery (median 87
      months; range, 24-121 months). Functional results were evaluated according to the
      Mayo Elbow Score. RESULTS: Fractures with complete joint involvement were seen
      most often. Taking the fracture type into consideration, functional results
      deteriorated with degree of joint involvement. Postoperative complication rate
      was high, predominantly seen as screw loosening and/or implant failure at the
      lateral column. Neverthless, functional results were preponderating good or
      excellent. Factors negatively influencing outcome were joint immobilization
      longer than 14 days and severe joint involvement. DISCUSSION: In elderly
      patients, distal humerus fractures, which are often considered "osteoporotic
      fractures," still remain one of the most demanding challenges in trauma surgery.
      The present study demonstrates that despite diminished bone quality and a high
      complication rate, open reduction and internal fixation in elderly patients is
      justified. CONCLUSION: Open reduction and internal fixation of distal humerus
      fractures in elderly patients should be the main goal, since good elbow function
      can be achieved in the majority of patients. Elbow immobilization longer than 14
      days should be avoided. Stable implant anchorage at the lateral column remains
      problematic, reflecting a general potential for further implant improvements.

PMID- 15517187
TI  - Knowledge about osteoporosis: assessment, correlates and outcomes.
AB  - During the last 10 years, we have witnessed an impressive increase in the number
      of studies examining knowledge about osteoporosis. The aim of the present paper
      is to examine the status of research on knowledge about osteoporosis by reviewing
      and analyzing the current literature as it pertains to assessment of knowledge
      about osteoporosis, factors associated with knowledge, and relationship between
      knowledge about osteoporosis and participation in health-related behaviors.
      Finally, future directions in the field are discussed. Many of the studies are
      still characterized by the lack of a theoretical framework, as well as by various
      methodological flaws. Serious deficits in knowledge are reported among healthy
      and diagnosed women and men, as well as among health professionals. Educational
      interventions are accompanied by an increase in knowledge, but no change in
      behavior. There is need to expand the research on knowledge about osteoporosis,
      especially in an effort to increase its impact on the prevention and early
      diagnosis of the disease. The deficits found in the knowledge of both the general
      population and among health care professionals, should be addressed by providing
      updated and reliable information through appropriate health promotion and
      professional venues.

PMID- 15517188
TI  - Bone gained from physical activity and lost through detraining: a longitudinal
      study in young males.
AB  - The aim of this study was to investigate the effect of training and detraining on
      bone mineral density of both weight-bearing and non-weight-bearing bone in a
      cohort of young males who participated in ice hockey training. Forty-three
      healthy adolescent ice hockey players (16.7+/-0.6 years) training for a mean of
      9.7+/-2.4 h/week and 25 control subjects (16.8+/-0.3 years) training for 2.1+/
      2.7 h/week, were included in this longitudinal study. Bone mineral density (BMD,
      g/cm2) of the arms, the dominant and non-dominant humerus, dominant and non
      dominant femur, and the right femoral neck, total hip, and bone area of the
      femur, humerus and hip were measured at baseline and again after 30 and 70 months
      using dual-energy X-ray absorptiometry. From baseline to the first follow-up,
      athletes gained significantly more BMD in the femoral neck (0.07 versus 0.03
      g/cm2) and arms (0.09 versus 0.06 g/cm2) compared with the controls (P = 0.04 for
      both). Between the first and the second follow-up, 21 ice hockey players stopped
      their active sports career. These men lost significantly more BMD at the femoral
      neck (-0.02 versus -0.10 g/cm2, P < 0.001), total hip (-0.05 versus -0.09, P =
      0.04), dominant (0.02 versus -0.03 g/cm2, P = 0.009) and non-dominant humerus
      (0.03 versus -0.01 g/cm2, P = 0.03) than the still active ice hockey players (n =
      22). At the second follow-up examination, at 22 years of age, the former ice
      hockey players still had significantly higher BMD at the non-dominant humerus
      than the controls (P < 0.01). During the total study period, the still active
      athletes (n = 22) gained significantly more BMD compared with the controls at the
      femoral neck (0.09 g/cm2; P = 0.008), total hip (0.05 g/cm2, P = 0.04) and arms
      (0.07 g/cm2; P = 0.01). No differences were seen in bone areas when comparing the
      different groups. In conclusion, training associated with ice hockey is related
      to continuous accumulation of BMD after puberty in males. Reduced activity is
      followed by BMD loss within 3 years of cessation of sports career at
      predominantly weight-bearing sites. The effects are confined to bone density and
      not bone size.

PMID- 15517190
TI  - A model of osteoporosis impact in Switzerland 2000-2020.
AB  - The aim of our study was to develop a modeling framework suitable to quantify the
      incidence, absolute number and economic impact of osteoporosis-attributable hip,
      vertebral and distal forearm fractures, with a particular focus on change over
      time, and with application to the situation in Switzerland from 2000 to 2020. A
      Markov process model was developed and analyzed by Monte Carlo simulation. A
      demographic scenario provided by the Swiss Federal Statistical Office and various
      Swiss and international data sources were used as model inputs. Demographic and
      epidemiologic input parameters were reproduced correctly, confirming the internal
      validity of the model. The proportion of the Swiss population aged 50 years or
      over will rise from 33.3% in 2000 to 41.3% in 2020. At the total population
      level, osteoporosis-attributable incidence will rise from 1.16 to 1.54 per 1,000
      person-years in the case of hip fracture, from 3.28 to 4.18 per 1,000 person
      years in the case of radiographic vertebral fracture, and from 0.59 to 0.70 per
      1,000 person-years in the case of distal forearm fracture. Osteoporosis
      attributable hip fracture numbers will rise from 8,375 to 11,353, vertebral
      fracture numbers will rise from 23,584 to 30,883, and distal forearm fracture
      numbers will rise from 4,209 to 5,186. Population-level osteoporosis-related
      direct medical inpatient costs per year will rise from 713.4 million Swiss francs
      (CHF) to CHF946.2 million. These figures correspond to 1.6% and 2.2% of Swiss
      health care expenditures in 2000. The modeling framework described can be applied
      to a wide variety of settings. It can be used to assess the impact of new
      prevention, diagnostic and treatment strategies. In Switzerland incidences of
      osteoporotic hip, vertebral and distal forearm fracture will rise by 33%, 27%,
      and 19%, respectively, between 2000 and 2020, if current prevention and treatment
      patterns are maintained. Corresponding absolute fracture numbers will rise by
      36%, 31%, and 23%. Related direct medical inpatient costs are predicted to
      increase by 33%; however, this estimate is subject to uncertainty due to limited
      availability of input data.

PMID- 15517189
TI  - Reducing the risk for distal forearm fracture: preserve bone mass, slow down, and
      don't fall!
AB  - A case-control study of 1,150 female and male distal forearm cases and 2,331
      controls of age 45 years and older was undertaken from 1996-2001 in five Northern
      California Kaiser Permanente Medical Centers. Most information on possible risk
      factors was obtained by an interviewer-administered questionnaire, supplemented
      by a few tests of lower extremity neurological function. Previous fractures since
      45 years of age, a rough marker of osteoporosis, were associated with an
      increased risk (adjusted odds ratio [OR] [95% confidence interval] = 1.48 [1.20
      1.84 ] per previous fracture). Several factors thought to protect against low
      bone mass were associated with a reduced risk, including current use of
      menopausal hormone therapy (adjusted OR = 0.60 [0.49-0.74]), ever used thiazide
      diuretics or water pills for at least 1 year (adjusted OR = 0.79 [0.64-0.97]),
      high body mass index (weight in kg/height in m2) (adjusted OR = 0.96 [0.89-1.04]
      per 5 unit increase), and high dietary calcium intake (adjusted OR = 0.88 [0.75
      1.03] per 500 mg/day). Falls in the past year and conditions associated with
      falling, such as epilepsy and/or use of seizure medication (adjusted OR = 2.07
      [1.35-3.17]) and a history of practitioner-diagnosed depression (adjusted OR =
      1.40 [1.13-1.73]), were associated with increased risks. Having difficulty
      performing physical functions and all lower-extremity problems measured in this
      study were associated with reduced risks. The results from this and other studies
      indicate that distal forearm fractures tend to occur in people with low bone mass
      who are otherwise in relatively good health and are physically active, but who
      are somewhat prone to falling (particularly on an outstretched hand), and whose
      movements are not slowed by lower extremity problems and other debilities. Thus,
      measures to decrease fall frequency and to slow down the pace of relatively
      healthy people with low bone mass should lead to a lower frequency of distal
      forearm fracture.

PMID- 15517191
TI  - Risk factors associated with incident clinical vertebral and nonvertebral
      fractures in postmenopausal women: the Canadian Multicentre Osteoporosis Study
      (CaMos).
AB  - Utilizing data from the Canadian Multicentre Osteoporosis Study (CaMos), we
      examined the association between potential risk factors and incident vertebral
      and nonvertebral fractures. A total of 5,143 postmenopausal women were enrolled.
      Information collected during the study included data from the CaMos baseline and
      annually mailed fracture questionnaires, the Short Form 36 (SF-36), the Health
      Utilities Index, and physical measurements. Participants were followed for 3
      years. Postmenopausal women were classified into four groups according to their
      incident fracture status since baseline: those without a new fracture; those with
      a new clinically recognized vertebral fracture; those with an incident
      nonvertebral fracture at the wrist, hip, humerus, pelvis, or ribs (main
      nonvertebral fracture group); and those with any new nonvertebral fracture (any
      nonvertebral-fracture group). We performed multivariate Cox proportional hazard
      analysis using all possible risk factors to determine the association between
      risk factors and the time to the first minimal trauma fracture. Best predictive
      models were also determined using variables that were included in the full
      models. The Bayesian information criterion was used for model selection. For all
      analyses, relative risks and associated 95% confidence intervals were calculated.
      During the follow-up period, 34, 163, and 280 women developed a vertebral, a main
      nonvertebral, or any nonvertebral fracture, respectively. The best predictive
      models indicated that a five point lower quality of life as measured by the SF-36
      physical component summary score was associated with relative risks of 1.21 (95%
      CI, 1.02 to 1.44), 1.17 (95% CI, 1.07 to 1.28), and 1.19 (95% CI, 1.11 to 1.27)
      for incident vertebral, main nonvertebral, and all nonvertebral fractures,
      respectively. In addition, for a one standard deviation (SD=0.12) lower femoral
      neck BMD, the relative risks for incident vertebral, main nonvertebral, and any
      nonvertebral fractures increased by 2.73 (95% CI, 1.74 to 4.28), 1.39 (95% CI,
      1.06 to 1.82), and 1.34 (95% CI, 1.09 to 1.65), respectively. Furthermore,
      various anthropometric measures, disease conditions, and medications are
      associated with a new fracture. Identifying postmenopausal women at risk is
      important given that fracture prevention therapies are now available.

PMID- 15517194
TI  - Dissociation of wanting and liking for alcohol in humans: a test of the incentive
      sensitisation theory.
AB  - RATIONALE: Incentive sensitisation theory (IST) claims that the mechanism of
      reward is comprised of separate neurobiological systems of wanting and liking,
      that dependent drug use occurs as a result of sensitisation of the system
      controlling wanting, and that the two systems can be dissociated. OBJECTIVE: To
      test the IST prediction that wanting and liking for alcohol can be dissociated in
      humans. METHODS: Measures of wanting and liking for alcohol were obtained in
      three experiments. Experiment 1 examined whether liking for alcohol was
      associated with levels of wanting, as indexed by self-reported weekly alcohol
      intake. Experiments 2 and 3 also assessed the association between liking and
      wanting but in these experiments wanting was also indexed by alcohol consumption
      in the laboratory. Experiment 2 increased wanting for alcohol using an alcohol
      priming dose to determine whether liking would be similarly affected. Experiment
      3 reduced liking for alcohol by adulterating drinks with Tween to see whether
      wanting would also be reduced. RESULTS: Little evidence for an association
      between liking and wanting for alcohol was found in Experiments 1-3 but,
      collapsing across all experiments, a weak positive correlation between liking and
      wanting was found. However, in Experiment 2, wanting was increased by the alcohol
      priming dose whereas liking was not and in Experiment 3 liking was reduced
      without a concurrent reduction in wanting. CONCLUSIONS: Although correlations
      between wanting and liking can be observed these results support the contention
      of the IST that wanting and liking for alcohol can be dissociated in human
      participants.

PMID- 15517197
TI  - Dealing with those on "the dark side"--difficult and worse people.

PMID- 15517198
TI  - Validation of a simplified field-adapted procedure for routine determinations of
      methyl mercury at trace levels in natural water samples using species-specific
      isotope dilution mass spectrometry.
AB  - A field-adapted procedure based on species-specific isotope dilution (SSID)
      methodology for trace-level determinations of methyl mercury (CH(3)Hg(+)) in
      mire, fresh and sea water samples was developed, validated and applied in a field
      study. In the field study, mire water samples were filtered, standardised
      volumetrically with isotopically enriched CH(3) (200)Hg(+), and frozen on dry
      ice. The samples were derivatised in the laboratory without further pre-treatment
      using sodium tetraethyl borate (NaB(C(2)H(5))(4)) and the ethylated methyl
      mercury was purge-trapped on Tenax columns. The analyte was thermo-desorbed onto
      a GC-ICP-MS system for analysis. Investigations preceding field application of
      the method showed that when using SSID, for all tested matrices, identical
      results were obtained between samples that were freeze-preserved or analysed
      unpreserved. For DOC-rich samples (mire water) additional experiments showed no
      difference in CH(3)Hg(+) concentration between samples that were derivatised
      without pre-treatment or after liquid extraction. Extractions of samples for
      matrix-analyte separation prior to derivatisation are therefore not necessary. No
      formation of CH(3)Hg(+) was observed during sample storage and treatment when
      spiking samples with (198)Hg(2+). Total uncertainty budgets for the field
      application of the method showed that for analyte concentrations higher than 1.5
      pg g(-1) (as Hg) the relative expanded uncertainty (REU) was approximately 5% and
      dominated by the uncertainty in the isotope standard concentration. Below 0.5 pg
      g(-1) (as Hg), the REU was >10% and dominated by variations in the field blank.
      The uncertainty of the method is sufficiently low to accurately determine
      CH(3)Hg(+) concentrations at trace levels. The detection limit was determined to
      be 4 fg g(-1) (as Hg) based on replicate analyses of laboratory blanks. The
      described procedure is reliable, considerably faster and simplified compared to
      non-SSID methods and thereby very suitable for routine applications of CH(3)Hg(+)
      speciation analysis in a wide range of water samples.

PMID- 15517195
TI  - Behavioral sensitization due to social defeat stress in mice: antagonism at
      mGluR5 and NMDA receptors.
AB  - RATIONALE: Repeated administration of psychostimulants progressively augments the
      behavioral response to and increases self-administration behavior of these drugs.
      Experience of repeated intermittent social defeat stress episodes also leads to a
      sensitized locomotor response following psychostimulant challenge. Both
      metabotropic and ionotropic glutamate receptors have been shown to be critical in
      the induction and expression of stimulant sensitization, but their role in
      sensitization due to social defeat stress remains unclear. OBJECTIVE: We
      evaluated the role of mGluR5 and NMDA glutamate receptors in the development of
      amphetamine-induced and social defeat stress-induced sensitization, using the non
      competitive mGluR5 antagonist, MPEP, and the non-competitive NMDA antagonist,
      dizocilpine (MK-801). METHODS: In adult, male CFW mice, sensitization was induced
      by either ten daily injections of D-amphetamine (1 mg/kg) or ten daily brief
      episodes of social defeat. Mice were pretreated with MPEP (3 mg/kg or 10 mg/kg)
      or dizocilpine (0.1 mg/kg) prior to amphetamine injections. Mice subjected to
      social defeat were pretreated with MPEP (10 mg/kg) or dizocilpine (0.1 mg/kg).
      Ten days after induction, the expression of locomotor sensitization to
      amphetamine was determined. RESULTS: The induction of sensitization due to social
      defeat stress was prevented by MPEP, yet MPEP did not inhibit the development of
      behavioral sensitization to amphetamine. Confirming and extending earlier
      results, dizocilpine pretreatment blocked both amphetamine-induced and stress
      induced sensitization. CONCLUSIONS: These data indicate that behavioral
      sensitization to social defeat stress is dependent on mGluR5 receptors, whereas
      low-dose amphetamine sensitization may not be.

PMID- 15517199
TI  - Metal fractionation of atmospheric aerosols via sequential chemical extraction: a
      review.
AB  - This review surveys schemes used to sequentially chemically fractionate metals
      and metalloids present in airborne particulate matter. It focuses mainly on
      sequential chemical fractionation schemes published over the last 15 years. These
      schemes have been classified into five main categories: (1) based on Tessier's
      procedure, (2) based on Chester's procedure, (3) based on Zatka's procedure, (4)
      based on BCR procedure, and (5) other procedures. The operational characteristics
      as well as the state of the art in metal fractionation of airborne particulate
      matter, fly ashes and workroom aerosols, in terms of applications, optimizations
      and innovations, are also described. Many references to other works in this area
      are provided.

PMID- 15517200
TI  - Determination of benzene, toluene, ethylbenzene and xylenes in air by solid phase
      micro-extraction/gas chromatography/mass spectrometry.
AB  - The aim of the study was to analyse BTEX compounds (benzene, toluene,
      ethylbenzene, xylenes) in air by solid phase micro-extraction/gas
      chromatography/mass spectrometry (SPME/GC/MS), and this article presents the
      features of the calibration method proposed. Examples of real-world air analysis
      are given. Standard gaseous mixtures of BTEX in air were generated by dynamic
      dilution. SPME sampling was carried out under non-equilibrium conditions using a
      Carboxen/PDMS fibre exposed for 30 min to standard gas mixtures or to ambient
      air. The behaviour of the analytical response was studied from 0 to 65 microg/m3
      by adding increasing amounts of BTEX to the air matrix. Detection limits range
      from 0.05 to 0.1 microg/m3 for benzene, depending on the fibre. Inter-fibre
      relative standard deviations (reproducibility) are larger than 18%, although the
      repeatability for an individual fibre is better than 10%. Therefore, each fibre
      should be considered to be a particular sampling device, and characterised
      individually depending on the required accuracy. Sampling indoor and outdoor air
      by SPME appears to be a suitable short-delay diagnostic method for volatile
      organic compounds, taking advantage of short sampling time and simplicity.

PMID- 15517201
TI  - Three-step extraction procedure for determination of heavy metals availability to
      vegetables.
AB  - A three-step sequential extraction procedure was used to determine the
      concentration of heavy metal speciation forms in soil. The procedure allows one
      to identify the pool of heavy metals that can be potentially mobilised under
      changes in soil pH value or redox potential. It has been shown that similar
      portions of heavy metals are present in reducible, oxidisable and residual
      fractions. It was found that soil chemical properties significantly affected the
      distribution of heavy metals among different fractions and their uptake by
      vegetables. Cadmium was a dominant element which occurred in the exchangeable
      fraction-the most bioavailable and potentially toxic.

PMID- 15517202
TI  - Passive sampling and/or extraction techniques in environmental analysis: a
      review.
AB  - The current state-of-the-art of passive sampling and/or extraction methods for
      long-term monitoring of pollutants in different environmental compartments is
      discussed in this review. Passive dosimeters that have been successfully used to
      monitor organic and inorganic contaminants in air, water, sediments, and soil are
      presented. The application of new approaches to the determination of pollutants
      at the sampling stage is discussed. The main milestones in the development of
      passive techniques for sampling and/or extraction of analytes, and in biomonitors
      used in environmental analysis, are summarized in this review. Passive samplers
      and biomonitors are compared.

PMID- 15517203
TI  - Solution to spectroscopy challenge 7.

PMID- 15517204
TI  - Spectroscopy challenge 8.

PMID- 15517205
TI  - Scanning electrochemical microscopy (SECM) of nanolitre droplets using an
      integrated working/reference electrode assembly.
AB  - Scanning electrochemical microscopy (SECM) has been performed in the restricted
      space of nanolitre droplets with a robust and easy-to-handle coaxial electrode
      assembly centring a Pt microdisk in a circular Ag electrode. Straightforward and
      reproducible fabrication of the specially designed probe tips was achieved by
      using Tollens' reaction to chemically deposit a uniform and well-adhering layer
      of silver on the body of a glass-insulated Pt microdisk electrode. The
      suitability of the novel dual-electrode SECM tip for measurement in small volumes
      was evaluated by imaging an array of four Pt band microelectrodes in 500 nL
      electrolyte.

PMID- 15517206
TI  - Measurement of labile Cu in soil using stable isotope dilution and isotope ratio
      analysis by ICP-MS.
AB  - Isotope dilution is a useful technique to measure the labile metal pool, which is
      the amount of metal in soil in rapid equilibrium (<7 days) with the soil
      solution. This is normally performed by equilibrating soil with a metal isotope,
      and sampling the labile metal pool by using an extraction (E value), or by
      growing plants (L value). For Cu, this procedure is problematic for E values, and
      impossible for L values, due to the short half-life of the 64Cu radioisotope
      (12.4 h), which makes access and handling very difficult. We therefore developed
      a technique using enriched 65Cu stable isotope and measurement of 63Cu/65Cu
      ratios by quadrupole inductively coupled plasma mass spectrometry (ICP-MS) to
      measure labile pools of Cu in soils using E value techniques. Mass spectral
      interferences in detection of 63Cu/65Cu ratios in soil extracts were found to be
      minimal. Isotope ratios determined by quadrupole ICP-MS compared well to those
      determined by high-resolution (magnetic sector) ICP-MS. E values determined using
      the stable isotope technique compared well to those determined using the
      radioisotope for both uncontaminated and Cu-contaminated soils.

PMID- 15517207
TI  - Determination of inorganic arsenic in white fish using microwave-assisted
      alkaline alcoholic sample dissolution and HPLC-ICP-MS.
AB  - An analytical method for the determination of inorganic arsenic in fish samples
      using HPLC-ICP-MS has been developed. The fresh homogenised sample was subjected
      to microwave-assisted dissolution by sodium hydroxide in ethanol, which dissolved
      the sample and quantitatively oxidised arsenite (As(III)) to arsenate (As(V)).
      This allowed for the determination of inorganic arsenic as a single species, i.e.
      As(V), by anion-exchange HPLC-ICP-MS. The completeness of the oxidation was
      verified by recovery of As(V) which was added to the samples as As(III) prior to
      the dissolution procedure. The full recovery of As(V) at 104 +/- 7% (n = 5)
      indicated good analytical accuracy. The uncertified inorganic arsenic content in
      the certified reference material TORT-2 was 0.186 +/- 0.014 ng g(-1) (n = 6). The
      method was employed for the determination of total arsenic and inorganic arsenic
      in 60 fish samples including salmon from fresh and saline waters and in plaice.
      The majority of the results for inorganic arsenic were lower than the LOD of 3 ng
      g(-1), which corresponded to less than one per thousand of the total arsenic
      content in the fish samples. For mackerel, however, the recovery of As(III) was
      incomplete and the method was not suited for this fat-rich fish.

PMID- 15517209
TI  - Development of an HPLC method for the identification and dosage of non-allowed
      substances in cosmetic products. Part I: local anaesthetics and antihistaminics.
AB  - An HPLC method with ultraviolet detection coupled with a solid-phase extraction
      sample clean up was developed for the analysis of five local anaesthetics and
      four antihistaminics in cosmetic products. The presence of these compounds in
      commercial cosmetic samples is fordbidden. Extracts from real samples were
      applied to a solid-phase extraction C18 cartridge, and the analytes were eluted
      with 8:2 (v/v) acetonitrile/water containing 1% trifluoroacetic acid. HPLC
      separation was then performed for the identification and determination of the
      analytes using a Purospher RP-18 column, two gradient eluting systems and a
      photodiode-array detector. The accuracy of the method was verified by spiking
      experiments on home-made cosmetic samples. The analytical recoveries were
      satisfactory.

PMID- 15517210
TI  - Simultaneous assay of glucose, lactate, L-glutamate and hypoxanthine levels in a
      rat striatum using enzyme electrodes based on neutral red-doped silica
      nanoparticles.
AB  - An electrochemical method suitable for the simultaneous measurement of cerebral
      glucose, lactate, L-glutamate and hypoxanthine concentrations from in vivo
      microdialysis sampling has been successfully performed for the first time using a
      neutral red-doped silica (NRDS) nanoparticle-derived enzyme sensor system. These
      uniform NRDS nanoparticles (about 50 +/- 3 nm) were prepared by a water-in-oil
      (W/O) microemulsion method, and characterized by a TEM technique. The neutral red
      doped interior maintained its high electron-activity, while the exterior nano
      silica surface prevented the mediator from leaching out into the aqueous
      solution, and showed high biocompability. These nanoparticles were then mixing
      with the glucose oxidase (GOD), lactate oxidase (LOD), L-glutamate oxidase (L
      GLOD) or xanthine oxidase (XOD), and immobilized on four glassy carbon
      electrodes, respectively. A thin Nafion film was coated on the enzyme layer to
      prevent interference from molecules such as ascorbic acid and uric acid in the
      dialysate. The high sensitivity of the NRDS modified enzyme electrode system
      enables the simultaneous monitoring of trace levels of glucose, L-glutamate,
      lactate and hypoxanthine in diluted dialysate samples from a rat striatum.

PMID- 15517211
TI  - Single-unit responses to kinetic stimuli in New World monkey area V2:
      physiological characteristics of cue-invariant neurones.
AB  - In order to investigate the neural processes underlying figure-ground segregation
      on the basis of motion, we studied the responses of neurones in the second visual
      area (V2) of marmoset monkeys to stimuli that moved against dynamic textured
      backgrounds. The stimuli were either "solid" bars, which were uniformly darker or
      lighter than the background's average, or kinetic ("camouflaged") bars, formed by
      textural elements that matched the spatial and temporal modulation of the
      background. Camouflaged bars were rendered visible only by the coherent motion of
      their textural elements. Using solid bars, we subdivided the population of
      marmoset V2 neurones into motion-selective (uni- and bi-directional units, 73.3%
      of the sample) and weakly-biased (26.7%) subpopulations. The motion selective
      subpopulation was further subdivided into cue-invariant neurones (units which
      demonstrated a similar selectivity for the direction of motion of the solid and
      camouflaged bars) and non-cue-invariant neurones (units which showed selectivity
      to the direction of motion of solid bars, but had weak or pandirectional
      responses to camouflaged bars). Cells with cue-invariant responses to these
      stimuli were as common in V2 as in the primary visual area (V1; approximately 40%
      of the population). In V2, neurones with cue-invariant and non-cue-invariant
      motion selectivity formed distinct populations in terms of classical response
      properties: cue-invariant neurones were characterized by a sharp axis of motion
      selectivity and extensive length summation, while the majority of non-cue
      invariant neurones had broader motion selectivity and were end-stopped. In the
      light of previous studies, these different constellations of classical response
      properties suggest a correlation with more traditionally recognized categories of
      V2 units and modular compartments. The responses of V2 cells to kinetic stimuli
      were slightly delayed relative to their responses to luminance-defined stimuli.

PMID- 15517212
TI  - No evidence of a lower visual field specialization for visuomotor control.
AB  - The lower visual field (loVF) has been hypothesized to demonstrate specialization
      for skilled, visually guided action. According to Danckert and Goodale, this
      visual field asymmetry indirectly suggests that the loVF has privileged
      connections to visuomotor networks within the dorsal visual pathway. Here we
      attempted to replicate the loVF advantage during the execution of a discrete
      aiming movement to targets of various widths (index of difficulty ranging from
      1.5 to 5 bits). In addition, we employed trials in which vision of the target
      object was available or unavailable during the reaching movement to determine
      whether or not the purported visual field asymmetry reflects enhanced central
      planning (i.e., feedforward) or online control (i.e., feedback) processes.
      Reaching trajectories were examined for indicators of online amendments, and
      movement times and endpoint characteristics were examined to quantify possible
      visual field asymmetries in relative speed/accuracy trade-offs. In terms of
      reaching kinematics, it was found that vision of the target during the reaching
      movement resulted in greater online control of the reaching trajectory; however,
      no significant main effects or interactions involving visual field were observed.
      In other words, fixating in the upper or the lower region of peripersonal space
      did not influence the nature of reaching control (i.e., feedback vs.
      feedforward). Most importantly, our movement time and endpoint accuracy data
      elicited a robust speed/accuracy trade-off in both upper and lower regions of
      working space. Thus, and contrary to previous findings (such as those reported by
      Danckert and Goodale), the indices of difficulty coupled with the discrete aiming
      task used here did not elicit a lower visual field advantage for visually guided
      action.

PMID- 15517213
TI  - The time and space of lexicality: a neuromagnetic view.
AB  - Illuminating the neural mechanisms subserving lexico-semantic processing is
      requisite to further understanding the neurophysiological basis of the dyslexias.
      Yet, despite numerous functional neuroimaging experiments, the location and
      temporal behavior of brain regions mediating word-level language processing
      remain an area of debate. Such investigations typically utilize the
      word/pseudoword contrast within hemodynamic measurements, and report several left
      hemisphere regions that respond more strongly to pseudowords but fail to
      replicate neural areas unique to real word processing. The present experiment
      addressed this problem from a different perspective. Mainly, we hypothesized that
      the time course, but not the neuroanatomy, would show within-subject across
      condition disparities. For that purpose, we applied dipole-modeling techniques to
      high-density magnetoencephalographic recordings of healthy subjects, and utilized
      excellent spatiotemporal accuracy to demonstrate significant across-condition
      differences in the time domain, along with indistinguishable neural correlates
      within-subject. In all participants, both words and pseudowords elicited activity
      in left perisylvian language areas, with words consistently activating these
      regions approximately 100 ms earlier than pseudowords. Considerable functional
      heterogeneity was also observed, and this might underlie the inconsistencies
      among previous studies. We conclude that the neural distinction in
      word/pseudoword processing is not in spatial localization, but is better
      conceptualized as a dynamic difference in processing time.

PMID- 15517214
TI  - Effects of practice on cardiorespiratory responses during postural control.
AB  - The present study examined the effects of practice of a balance test on
      cardiorespiratory changes in response to a 1-min balance test performed by
      standing on one leg with eyes closed (SOLEC) in 30 females (n=15, 21+/-4 years,
      mean+/-SD, for the experimental group; n=15, 22+/-4 years for the control group).
      Blood pressure (BP), heart rate (HR), minute ventilation (VE), respiratory rate
      (RR), tidal volume (VT), expiratory duration (Te), inspiratory duration (Ti), and
      oxygen uptake (VO(2)) were measured during the balance test before and after 2 wk
      of daily practice. The experimental group was given a daily 15-min practice
      session for the balance test. In contrast, the control group was instructed not
      to do any special practice for the balance test. In both the experimental and
      control groups, SOLEC induced significant increases in BP, HR, VE, RR, and VO(2),
      and decreases in Te and Ti. Following the practice sessions, the balance time
      increased significantly in the experimental group (P<0.01). In addition, 2 wk of
      practice reduced the increases in BP (P<0.01), VE (P<0.05), and RR (P<0.01), and
      prolonged Te (P<0.01) during the SOLEC test. These results suggest that practice
      of a postural task affects cardiorespiratory responses to the balance test in
      addition to postural control.

PMID- 15517215
TI  - Visual afferent information dominates other sources of afferent information
      during mixed practice of a video-aiming task.
AB  - The goal of the present study was to determine whether learning of a manual video
      aiming task that would have to be performed in a target-only condition (transfer
      test) would be improved, unaffected or hindered by alternating practice between a
      normal vision and a target-only condition. The results of the present study
      indicate that a mixed schedule of practice hindered learning of the task.
      Specifically, participants who practiced the task in the mixed schedule showed
      larger direction constant error in transfer than participants who practiced only
      in the target-only condition. The results suggest that participants in the mixed
      condition continued to rely on the rapidly decaying information that was
      extracted in the normal vision condition to plan and control their movement in
      the target-only condition, which ultimately led to biased movement endpoints.

PMID- 15517216
TI  - Changes in corticomotor excitability of hand muscles in relation to static
      shoulder positions.
AB  - We examined whether the recruitment properties of the corticospinal pathway to
      intrinsic hand muscles are influenced by variations of the shoulder joint angle.
      Abductor digiti minimi (ADM) motor evoked potentials (MEPs) in response to
      transcranial magnetic stimulation were examined during different static positions
      of the shoulder joint in the horizontal plane from 30 degrees adduction to 30
      degrees abduction with respect to the neutral position at 0 degrees, while elbow
      and wrist joints were constrained statically at 90 degrees and 180 degrees
      respectively. We found that 30 degrees abduction of the shoulder significantly
      depressed MEP size and prolonged MEP latency in comparison with 30 degrees
      shoulder adduction. The neutral shoulder angle position (at 0 degrees )
      significantly reduced MEP size but had no effect on MEP latency in comparison
      with 30 degrees shoulder abduction. The input-output relationship between MEP
      size and stimulus intensity was sigmoidal. The plateau value and maximum slope
      were significantly lower at 30 degrees abduction than at 30 degrees adduction of
      the shoulder. However, the threshold value did not differ significantly between
      the two positions. To differentiate excitability changes at cortical versus
      subcortical sites, intracortical inhibition (ICI) and intracortical facilitation
      (ICF) were assessed using a paired-magnetic pulse paradigm. A significant
      decrease in ICF was observed after changing shoulder position from 30 degrees
      adduction to 30 degrees abduction. In contrast, no variation in the amount of ICI
      occurred in relation to the same changes in shoulder position. ADM F-waves
      elicited by electrical stimulation of the ulnar nerve at the wrist were
      significantly decreased at 30 degrees shoulder abduction in comparison with 30
      degrees adduction. A similar pattern was observed in one subject in whom the H
      reflex could be exceptionally elicited in ADM. We conclude that shoulder position
      influences the recruitment efficiency (gain) of the corticospinal volleys to
      motoneurons of intrinsic hand muscles. It is proposed that activity of peripheral
      receptors signalling static shoulder position influences corticomotor
      excitability of hand muscles both at the cortical and at the spinal level. This
      modulation may be functionally relevant when reaching to grasp objects.

PMID- 15517217
TI  - The temporal organization of posture changes during the first year of independent
      walking.
AB  - Although the development of upright posture has received considerable attention,
      the quiet stance of infants in their first months of learning this fundamental
      behavior has not been well studied. The purpose of the present study was to
      characterize the time evolutionary properties, or temporal organization, of these
      infants' unperturbed upright stance as well as to elucidate how somatosensory
      information influences that organization. Six healthy, full-term infants were
      tested monthly from walk onset until 9 months of independent walking experience
      while standing either independently or touching a static surface. The structure
      of sway was assessed through stabilogram-diffusion analysis using an exponential
      Ornstein-Uhlenbeck characterization. The results of this analysis revealed two
      new insights into postural development. First, the developmental changes in quiet
      stance involved a decreased rate at which sway decays to maximal variance, rather
      than an attenuation of the magnitude of that variance. Specifically, measures
      indexing amount of sway variance were significantly reduced when touching a
      static surface as compared with an independent stance condition, but revealed no
      change with increased walking experience. Further, a reduction in the average
      rate constant of decay indicated an increased influence of long time-scale sway
      corrections on the overall sway trajectory. Second, it was shown that, at early
      walk ages, the use of touch both reduced the amount of variance and shifted the
      rate constant of sway towards longer time-scale displacements. Taken in the
      context of previous research, these results support our conclusion that early
      postural development embodies the dual tasks of calibrating sensorimotor
      relations for estimation of self-motion as well as identification and tuning of
      control system properties.

PMID- 15517218
TI  - The presence of an obstacle influences the stepping response during induced trips
      and surrogate tasks.
AB  - Falling is a frequent cause of serious injury in older adults and trips are a
      dominant cause of falls in this rapidly growing population. Although there are
      few laboratory protocols that induce actual trips, there are many protocols that
      utilize surrogate tasks. These surrogate tasks, which are time-critical but do
      not involve an obstacle, appear to share a number of biomechanical
      characteristics with stepping responses following a trip. However, although rapid
      and safe negotiation of the obstacle and restoration of dynamic equilibrium are
      common requisites for success, we expected that stepping response kinematics
      during a successful recovery from a trip over a previously unseen obstacle would
      be substantially different than those of surrogate tasks without an obstacle.
      Unexpected trips were induced in 13 older men and women by an obstacle, the
      presence of which the subjects were previously unaware. Selected kinematics of
      the leading and trailing limb stepping responses during recovery from the induced
      trip were compared to those of two surrogate tasks that did not involve an
      obstacle. Multivariate analysis of variance (MANOVA) revealed that step height,
      step length, peak horizontal velocity, and peak vertical velocity of the leading
      and trailing limbs were significantly different during recovery from the induced
      trip compared to the surrogate tasks. These between-task performance differences
      may limit the extent to which performance of the surrogate tasks accurately and
      precisely reflect the potential to recover dynamic equilibrium following a trip.
      Therefore, these findings may be applicable in the design of new or modification
      of existing interventions to reduce falls in older adults.

PMID- 15517219
TI  - Visual feedback alters the variations in corticospinal excitability that arise
      from rhythmic movements of the opposite limb.
AB  - Augmented visual feedback can have a profound bearing on the stability of
      bimanual coordination. Indeed, this has been used to render tractable the study
      of patterns of coordination that cannot otherwise be produced in a stable
      fashion. In previous investigations (Carson et al. 1999), we have shown that
      rhythmic movements, brought about by the contraction of muscles on one side of
      the body, lead to phase-locked changes in the excitability of homologous motor
      pathways of the opposite limb. The present study was conducted to assess whether
      these changes are influenced by the presence of visual feedback of the moving
      limb. Eight participants performed rhythmic flexion-extension movements of the
      left wrist to the beat of a metronome (1.5 Hz). In 50% of trials, visual feedback
      of wrist displacement was provided in relation to a target amplitude, defined by
      the mean movement amplitude generated during the immediately preceding no
      feedback trial. Motor potentials (MEPs) were evoked in the quiescent muscles of
      the right limb by magnetic stimulation of the left motor cortex. Consistent with
      our previous observations, MEP amplitudes were modulated during the movement
      cycle of the opposite limb. The extent of this modulation was, however, smaller
      in the presence of visual feedback of the moving limb (FCR omega2=0.41; ECR
      omega2=0.29) than in trials in which there was no visual feedback (FCR
      omega2=0.51; ECR omega2=0.48). In addition, the relationship between the level of
      FCR activation and the excitability of the homologous corticospinal pathway of
      the opposite limb was sensitive to the vision condition; the degree of
      correlation between the two variables was larger when there was no visual
      feedback of the moving limb. The results of the present study support the view
      that increases in the stability of bimanual coordination brought about by
      augmented feedback may be mediated by changes in the crossed modulation of
      excitability in homologous motor pathways.

PMID- 15517220
TI  - Saccades to stationary and moving targets differ in the monkey.
AB  - Saccade characteristics in response to moving and stationary targets were studied
      in three monkeys (Macaca mulatta) that had been trained to look at a target,
      which after an initial jump either remained in place or moved forward or backward
      with constant velocity (10 degrees /s). Eye movements were recorded using a
      search coil. The contribution of smooth pursuit to the saccade amplitude was
      small (<0.25 degrees ). Saccades having the same amplitude (5.67-6.83 degrees for
      different monkeys) to forward and backward moving targets were compared. Peak
      velocity was higher (37-42 degrees /s on average for different monkeys) and
      saccade duration was shorter (8-10 ms on average) for backward saccades than for
      forward saccades These differences were highly significant (t-test: P<0.001).
      Thus, forward and backward saccades are not on the same main sequence. This
      suggests that saccade dynamics are affected not only by the retinal position
      error but also by target motion. Further analysis revealed that saccade peak
      velocity mainly depends on the retinal position error, but saccade amplitude also
      depends on a stimulus-related velocity factor, which affects the saccade mainly
      during deceleration. This velocity factor could be retinal slip or target
      velocity, which was the same under our conditions. Our results experimentally
      support recent models that propose that the saccade acceleration in response to
      moving targets might be controlled by the superior colliculus, whereas the
      deceleration changes are fine-tuned by the cerebellum. This prediction must still
      be tested on a neuronal level.

PMID- 15517221
TI  - The effect of postural stability and spatial orientation of the upper limbs on
      interlimb coordination.
AB  - It has recently been reported that the spatial orientation of two moving limbs
      has a determining influence on the relative accuracy and stability of
      coordination patterns. The purpose of the present experiments was to test
      perceptual and neuromuscular explanations of these spatial orientation effects.
      Experiment 1 was an initial test of the hypotheses and an extension of a previous
      study [Lee et al. (2002) Exp Brain Res 146:205-212] that required participants to
      coordinate inphase and antiphase movement patterns in four spatial orientations:
      two symmetric orientations (90 degrees and 180 degrees separation between the
      limbs) and two asymmetric orientations (90 degrees and 135 degrees separation
      between the limbs). Results of Experiment 1 suggest that the symmetry of movement
      may be a key factor influencing spatial orientation effects observed during
      interlimb coordination. In Experiment 2, participants again performed inphase and
      antiphase movement patterns in symmetric and asymmetric spatial orientations.
      However, one-half of the participants in Experiment 2 were provided with
      mechanical constraints during the performance of the desired coordination
      patterns. The mechanical constraints provided postural support but did not
      influence the visual experience. Results showed that the addition of the postural
      support improved performance. These findings suggest that neuromuscular, and
      perhaps biomechanical, constraints contribute more to the influence of spatial
      orientation than visual-perceptual constraints.

PMID- 15517222
TI  - Step characteristics during obstacle avoidance in hemiplegic stroke.
AB  - Whereas several animal studies have indicated the important role of the motor
      cortex in the control of voluntary gait modifications, little is known about the
      effects of cortical lesions on gait adaptability in humans. Obstacle avoidance
      tasks provide an adequate paradigm to study the adaptability of the stepping
      pattern under controlled, experimental conditions. In the present study, an
      exploratory assessment was made of the failure rate, the preferred stepping
      strategies (step lengthening vs step shortening), and the spatiotemporal stride
      characteristics (percentage increases in stride length, duration, and velocity of
      the crossing and postcrossing strides) during obstacle avoidance in 11 hemiplegic
      stroke patients and seven healthy controls. Patients were less successful in
      avoiding obstacles than controls (14% failure rate vs 0.5% in controls),
      independent of whether the affected or the unaffected leg led the obstacle
      avoidance. The number of failed trials increased systematically when the
      available response time became shorter. During successful trials, lengthening of
      the step was generally preferred over shortening. This bias towards step
      lengthening was more pronounced in stroke patients (step lengthening in 91% of
      the trials vs 75% in controls), irrespective of the side of obstacle
      presentation. For both groups, overall strategy preference did not adhere to a
      principle of minimal foot displacement, since step lengthening was used even if
      it would be more spatially efficient to shorten the step. No statistically
      significant group differences were found for the increases in length, duration,
      and velocity of the crossing and postcrossing strides. However, for a subgroup of
      more slowly walking patients, large percentage increases were found in crossing
      stride length, duration, and velocity. Similar results were obtained for the
      postcrossing stride, indicating that, for this subgroup of patients, restoration
      of the normal walking cadence was more difficult. Overall, no systematic
      differences were found between the affected and the unaffected leg in stroke
      patients with respect to failure rates, stepping strategies, or spatiotemporal
      measures of obstacle avoidance. The present findings suggest that the ability to
      adequately modify the stepping pattern in response to imposed spatiotemporal
      constraints is impaired in persons with stroke, especially when modifications
      have to be performed under time pressure. In addition, the stepping strategies
      employed by subjects with stroke are different from those found in controls,
      possibly to reduce the complexity of the avoidance maneuver and to enhance
      safety. Finally, unilateral cortical damage results in an impaired ability to
      avoid obstacles on both sides of the body, suggesting that the reduced ability of
      stroke patients to negotiate obstacles may be related to problems of a more
      general coordinative nature.

PMID- 15517223
TI  - Modulation of cutaneous reflexes in human upper limb muscles during arm cycling
      is independent of activity in the contralateral arm.
AB  - The amplitudes and signs of cutaneous reflexes are modulated during rhythmic
      movements of the arms and legs (during walking and arm or leg cycling for
      instance). This reflex modulation is frequently independent of the background
      muscle activity and may involve central pattern generator (CPG) circuits. The
      purpose of the present study was to investigate the nature and degree of coupling
      between the upper limbs during arm cycling, with regard to the regulation of
      cutaneous reflexes. Responses to electrical stimulations of the right,
      superficial radial nerve (five 1 ms pulses, 300 Hz) were recorded bilaterally in
      six arm muscles of eight participants during arm cycling involving only the limb
      ipsilateral to the stimulation, only the limb contralateral to the stimulation,
      and bilateral movement when the limbs were both in-phase and 180 degrees out of
      phase. The pattern of cutaneous reflex modulation throughout the arm cycle was
      independent of the functional state of the limb contralateral to the recording
      site, irrespective of whether recordings were made ipsilateral or contralateral
      to the stimulation. Furthermore, cutaneous reflexes were significantly (p<0.05)
      modulated with arm position in only 8% of cases in which the limb containing the
      responding muscle was either stationary or being moved passively by the
      experimenter. The results show that there is relatively weak coupling between the
      arms with regard to the regulation of cutaneous reflexes during rhythmic,
      cyclical arm movements. This suggests a loose connection between the CPGs for
      each arm that regulate muscle activity and reflex amplitude during rhythmic
      movement.

PMID- 15517224
TI  - Stability and change in perception: spatial organization in temporal context.
AB  - Perceptual multistability has often been explained using the concepts of
      adaptation and hysteresis. In this paper we show that effects that would
      typically be accounted for by adaptation and hysteresis can be explained without
      assuming the existence of dedicated mechanisms for adaptation and hysteresis.
      Instead, our data suggest that perceptual multistability reveals lasting states
      of the visual system rather than changes in the system caused by stimulation. We
      presented observers with two successive multistable stimuli and found that the
      probability that they saw the favored organization in the first stimulus was
      inversely related to the probability that they saw the same organization in the
      second. This pattern of negative contingency is orientation-tuned and occurs no
      matter whether the observer had or had not seen the favored organization in the
      first stimulus. This adaptation-like effect of negative contingency combines
      multiplicatively with a hysteresis-like effect that increases the likelihood of
      the just-perceived organization. Both effects are consistent with a probabilistic
      model in which perception depends on an orientation-tuned intrinsic bias that
      slowly (and stochastically) changes its orientation tuning over time.

PMID- 15517225
TI  - Pattern of NSAID use in the Italian general population: a questionnaire-based
      survey.
AB  - BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most
      widely used medicines in the developed countries. The most important adverse
      reactions involve the upper gastrointestinal tract and can be life threatening. A
      detailed knowledge of the pattern of use of NSAIDs may help doctors in advising
      their patients about appropriateness and safety of use. AIM: The aim of the
      present survey was to evaluate the prevalence and pattern of NSAID use in the
      general population, as well as the main characteristics of NSAID users. METHODS:
      Between March and September 2002, a self-administered questionnaire was submitted
      to a random sample, stratified by gender and age, representative of the Italian
      adult population (n=3,250). The questionnaire was divided into three parts
      regarding: (1) sociodemographic information, (2) symptoms/illnesses and (3) any
      drug taken during the previous week and the corresponding purpose. A statistical
      analysis (logistic regression) was performed. RESULTS: Of the 2,738 subjects who
      filled in the questionnaire, 65% took at least one drug in the previous week and,
      among them, 35% used NSAIDs (top drug class; n=633). Of the NSAID users, 20% were
      >/=65 years of age and 18% were chronic users (daily or frequent use for more
      than 6 months). NSAID use was significantly higher in women, both for overall and
      chronic use. The older age groups showed an increasing risk of chronic NSAID use.
      Among NSAIDs, nimesulide was the most used compound (35%) followed by
      acetylsalicylic acid (14%) and ibuprofen (11%). The main reasons for NSAID use,
      as reported by subjects, were: headache (25%), osteoarticular pain (19%),
      unspecified pain (15%) and osteoarthrosis (9%). More than 50% of all the NSAIDs
      were prescribed by physicians (general practitioner, specialist, hospital
      physician), whereas about 44% were taken as self-treatment or following the
      advice of a pharmacist, relative/friend, etc. CONCLUSIONS: Our study confirms
      that NSAIDs are widely used in the Italian general population and that, in most
      cases, they are used in accordance with their approved indications. However,
      their large and often chronic use in the elderly, as well as the high frequency
      of self-treatment, recommends a higher awareness by all physicians.

PMID- 15517226
TI  - Prescribing indicators. Development and validation of guideline-based prescribing
      indicators as an instrument to measure the variation in the prescribing behaviour
      of general practitioners.
AB  - BACKGROUND: Differences in prescribing behaviour among general practitioners
      (GPs). AIM: To formulate and validate clinical prescribing indicators based on
      general practice guidelines. DESIGN: Validatory study. SETTING: Pharmacies and
      general practices in the Netherlands in 2003. PARTICIPANTS: A total of 379
      pharmacies, 947 general practices and 3.8 million patients. METHODS: A total of
      51 potential indicators were formulated, based on medicinal recommendations from
      the evidence-based guidelines of the Dutch College of General Practitioners and
      the corresponding recommendations from the Commission Pharmaceutical Help of the
      Health Care Insurance Board. These indicators were submitted to an expert panel
      to assess content validity. The panel assessment was analysed using the RAND-UCLA
      appropriateness method (RAM). Then, for the remaining indicators, it was assessed
      to what extent these could be used to determine the prescribing behaviour of GPs
      and the level to which this behaviour varies among GPs. This was done using a
      prescribing analyses and cost (PACT) database that was compiled from prescription
      databases from 379 pharmacies, with all prescriptions from 1,434 GPs over an
      entire year to 3.8 million patients. RESULTS: The panel considered 34 of the 51
      potential indicators to be valid with respect to providing an adequate reflection
      of the central recommendations in the guideline and in terms of relevance with
      respect to health gain and/or efficiency. Of these 34 indicators, 20 revealed
      considerable differences in the prescribing behaviour of GPs. CONCLUSION: On the
      basis of existing general practice guidelines, 20 prescribing indicators could be
      formulated that were assessed by an expert panel to be sufficiently valid and
      which could also discriminate the prescribing behaviour of GPs as reflected in
      the prescription databases of pharmacies.

PMID- 15517227
TI  - Upper gastrointestinal adverse drug reactions and cyclo-oxygenase-2 inhibitors
      (celecoxib and rofecoxib): a case/non-case study from the French
      Pharmacovigilance Database.
AB  - OBJECTIVE: To evaluate the gastrointestinal safety of cyclo-oxygenase-2
      inhibitors under their real conditions of use. DESIGN. Case/non-case study.
      SETTING: Adverse drug reactions (ADRs) in adults recorded in the French
      Pharmacovigilance Database between 25 May 2000 and 31 December 2002. MATERIALS:
      Cases were all reports of "serious" oeso-gastro-duodenal ADRs (oeso-gastro
      duodenal ulcers, oesophagitis, gastritis, duodenitis). Five non-cases were
      randomly selected for one case from all other non oeso-gastro-duodenal reports in
      the database after matching them for age, gender and period of occurrence.
      ANALYSIS: Coxib exposure was compared among cases and non-cases, with adjustment
      for matching factors: French Regional Pharmacovigilance Centres that collected
      ADRs, reporter health professional's characteristics and exposures to non
      selective non-steroidal anti-inflammatory, aspirin, anticoagulant, antiplatelet
      and gastroprotective drugs. RESULTS: Included in the study were 505 cases and
      2,525 non-cases. A positive association was found between occurrence of oeso
      gastro-duodenal ADRs and coxib (adjusted odds ratio 14.9 [95% CI 9.3-23.7]),
      diclofenac (9.2 [3.8-22.2]), ibuprofen (7.3 [3.2-16.6]) or oxicam (25.3 [11.9
      53.6]) use. CONCLUSION: Despite the compulsory limits of the case/non-case
      methodology, the present study shows that coxibs did induce "serious"
      gastrointestinal ADRs in real clinical practice. These results underline the need
      for pharmacoepidemiological studies under real conditions of use in order to
      verify (or not) the conclusions of clinical trials.

PMID- 15517228
TI  - Central neurocytoma: a clinicopathological and neuroradiological study.
AB  - Central neurocytoma (CNC) is an uncommon benign tumor of the central nervous
      system (CNS) occurring in adults and is more likely to be located in the region
      of the foramina of Monra. Few studies have described the neuroradiological
      features of CNC, and most are single case reports. Our aim was to analyze the
      clinicopathological and neuroradiological characteristics of CNC. We
      retrospectively studied the preoperative CT (n=2) and MRI (n=5) of three men and
      two women (mean age 45 years, ranging from 30 to 63 years) with pathologically
      proven CNC. The tumors were primarily located in the region of the foramina of
      Monra. Two of them occupied the lateral ventricle, appearing to be attached to
      the septum pellucidum, and the other three tumors arose from the septum
      pellucidum and extended into the lateral ventricles. The tumors were of mixed
      density with cystic features and patchy or fine calcification on noncontrast CT
      scans, and they were of low or isointense signal on T1- and heterogeneously
      hyperintense signal on T2- and FLAIR weighted images. Contrast enhancement varied
      greatly from very slight to intense. Immunohistochemical staining showed a
      positive reaction for synaptophysin (Syn), neuro-specific enclase (NSE),
      neurofilament protein (NF) in the tumor cells and glial fibrillary acid protein
      (GFAP) in the fibrillar zones. CNC should be taken into consideration first if a
      tumor arises from the region of the foramina of Monra with CNC neuroradiological
      characteristics and the patient is an adult.

PMID- 15517229
TI  - Influence of the site of arterial occlusion on multiple baseline hemodynamic MRI
      parameters and post-thrombolytic recanalization in acute stroke.
AB  - In this prospective MRI study, we evaluated the impact of the site of occlusion
      on multiple baseline perfusion parameters and subsequent recanalization in 49
      stroke patients who were given intravenous tissue plasminogen activator (tPA).
      Pretreatment magnetic resonance angiography (MRA) revealed an arterial occlusion
      in 47 patients: (1) internal carotid artery (ICA) + M1 middle cerebral artery
      (MCA) occlusion (n=12); (2) M1 MCA occlusion (n=19); (3) M2 MCA, distal branches
      of the MCA and anterior cerebral artery (ACA) occlusion (n=16). Patients with ICA
      occlusion had significantly larger DWI, PWI and mismatch lesion volume on
      pretreatment MRI compared to patients with other sites of occlusion. The
      differences in cerebral blood flow (CBF) and peak height were significantly
      higher in patients with ICA occlusion compared to patients with other sites of
      occlusion (P=0.03 and P=0.04, respectively). Day 1 MRA showed recanalization in
      28 patients (60%). The rate of recanalization was significantly different
      depending on the site of occlusion: 33% in ICA + M1 MCA occlusion, 63% in M1 MCA
      occlusion and 81% in either M2 MCA, distal branches of the MCA or ACA occlusion
      (P=0.002). Our data suggest that CBF and peak height are the most relevant MRI
      parameters to assess the severity of hemodynamic impairment in regard to the site
      of occlusion.

PMID- 15517230
TI  - Matrix metalloproteinases as diagnostic (MMP-13) and prognostic (MMP-2, MMP-9)
      markers of prostate cancer.
AB  - Previous studies have detected high levels of matrix metalloproteinases (MMPs) in
      metastatic prostate cancer. In this study, we recruited 40 patients with prostate
      cancer (PCa): 20 presented organ-confined carcinoma and 20 had metastatic cancer.
      We also recruited 40 subjects for control groups, 20 with benign prostate
      hyperplasia (BPH) and 20 healthy males with similar characteristics. All of the
      patients were monitored at the beginning (time 0) and after 90 days. We analyzed
      the plasma concentrations of MMP-2, MMP-9, MMP-13, TIMP-1 and the enzyme activity
      of MMP-2 and MMP-9,using specific ELISA tests. The plasma concentrations of MMP
      2, MMP-9 and MMP-13 were higher in PCa patients with metastasis than in the other
      groups, and in these patients decreased markedly after therapy began. For MMP-2
      and MMP-9, greater differences were observed in enzyme activity than in plasma
      concentrations. TIMP-1 was reduced in PCa patients with metastasis, even if the
      intergroup differences were not statistically significant. Our results suggest
      that the plasma concentration and activity of MMPs, in association with PSA
      determination, could play a role in diagnosis, monitoring therapy and evaluating
      malignant progression in PCa.

PMID- 15517232
TI  - MR imaging of abdominopelvic involvement in neurofibromatosis type 1: a review of
      43 patients.
AB  - BACKGROUND: Plexiform neurofibromas are a frequent complication of
      neurofibromatosis type 1. This article discusses MR imaging findings and
      distribution of plexiform neurofibromas in the abdomen and pelvis. OBJECTIVE: To
      define the most prevalent patterns of involvement and MR imaging findings in
      abdominopelvic neurofibromatosis type 1. MATERIALS AND METHODS: We reviewed the
      MR appearance of abdominopelvic lesions in 23 male and 20 female patients (median
      age: 16 years) with type 1 neurofibromatosis. The patients were part of a multi
      institutional study of 300 patients. Imaging included coronal or sagittal, and
      axial short tau inversion recovery images. RESULTS: The most common
      abdominopelvic involvement was in the abdominopelvic wall (n=28, 65%) and
      lumbosacral plexus (n=27, 63%). Retroperitoneal involvement was frequent (n=15,
      35%). Lesions were less often intraperitoneal (21%) (P=0.001). Pelvic disease
      (n=27, 63%), neural canal involvement (n=18, 42%), and hydronephrosis (n=4, 9%)
      were also noted. Target-like appearance of plexiform lesions was noted in more
      than half the patients. CONCLUSION: Abdominopelvic involvement in
      neurofibromatosis type 1 is primarily extraperitoneal. Although lesions are most
      prevalent in the abdominopelvic wall and lumbosacral plexus, retroperitoneal and
      pelvic involvement is common and usually affects important organs. MR imaging
      added information in the initial and follow-up clinical evaluation of these
      patients.

PMID- 15517231
TI  - Afferent bladder nerve activity in the rat: a mechanism for starting and stopping
      voiding contractions.
AB  - The objective of this work was to study the relation between afferent bladder
      nerve activity and bladder mechanics and the mechanisms that initiate and
      terminate bladder contractions. Bladder nerve activity, pressure and volume were
      recorded during the micturition cycle in the rat. The highest correlation was
      found between afferent nerve activity and stress (pressure x volume). Afferent
      nerve activity depended linearly on stress within 6%, and both slope and offset
      were independent of the bladder-filling rate. The levels of afferent bladder
      nerve activity at the onset and cessation of efferent firing to the bladder were
      highly reproducible with coefficients of variation of <or=17%. We propose a model
      in which afferent activity is proportional to bladder wall stress, and bladder
      contraction is initiated when afferent activity exceeds a threshold due to an
      increasing pressure and volume. The contraction continues until afferent activity
      drops below a threshold again as a result of a decreasing volume.

PMID- 15517233
TI  - Giant Meckel's diverticulum associated with oesophageal atresia, tracheo
      oesophageal fistula and cleft lip and palate.

PMID- 15517234
TI  - Gadolinium-enhanced magnetic resonance angiography of right ventricle to
      pulmonary artery shunts following Norwood 1 palliation in infants.
AB  - The classic Norwood I palliation for the treatment of hypoplastic left-heart
      disease includes an atrial septectomy, neoaorta creation, and a systemic-to
      pulmonary artery shunt. The Norwood I palliation has been modified by the use of
      a right ventricle-to-pulmonary artery shunt instead of a traditional systemic-to
      pulmonary artery shunt. Right ventricle-to-pulmonary artery shunts were non
      invasively imaged in four infants using gadolinium-enhanced magnetic resonance
      angiography. Diagnostic MR angiograms were performed in all infants throughout
      the length of the shunt and were useful in the detection of shunt patency,
      stenosis, and aneurysm. Associated surgical conduits and shunts were also
      evaluated. All findings were verified by subsequent conventional angiography or
      surgery.

PMID- 15517236
TI  - PEDBONE: the online reference database in paediatric plain film radiography.

PMID- 15517237
TI  - The gold standard: PACS alchemy and the gold standard.

PMID- 15517238
TI  - Ultrasonography of the annular ligament partial tear and recurrent "pulled
      elbow".
AB  - A 2-year-old boy had multiple episodes of radial head subluxation, recurrent
      "pulled elbow." On initial ultrasonography, there was subluxation of the radial
      head in relation to the capitellum, and the annular ligament was partially
      disrupted. Following brace treatment, subluxation of the radial head was
      corrected and annular ligament disruption healed. As shown by ultrasonography,
      these findings correlated well with the clinical course and can be utilized to
      guide treatment.

PMID- 15517239
TI  - Can peak systolic velocities be used for prediction of stroke in sickle cell
      anemia?
AB  - BACKGROUND AND PURPOSE: Ischemic stroke occurs in at least 11% of patients with
      homozygous sickle cell anemia (SCD) by the time they turn 20 years old. High risk
      associated with distal intracranial internal carotid (ICA) and proximal middle
      cerebral artery (MCA) stenosis can be detected by transcranial Doppler (TCD). TCD
      screening offers the possibility of reducing the risk of first stroke
      significantly based on a paradigm tested and proven to be effective in a stroke
      prevention trial in sickle cell anemia (STOP). Children with high flow velocity
      in the ICA and MCA of 200 cm/s time average mean of the maximum (TAMM) or higher
      had a 10% per year risk of first stroke that was reduced to <1% with regular red
      cell transfusion (reduction of hemoglobin S <30%). The clinical application of
      the STOP results could be enhanced if criteria for treatment could be found that
      are based on peak systolic velocity (PSV), the measure more commonly used in
      vascular ultrasound practice. OBJECTIVE: To compare PSV and end diastolic
      velocity (EDV) with TAMM for prediction of stroke and to derive PSV cutpoints for
      STOP protocol definitions of conditional and abnormal TCD. Using the STOP TCD and
      stroke outcome data to compare PSV and TAMM in terms of stroke prediction, PSV
      cutpoints comparable to those based on TAMM and used in STOP were derived.
      Because of their familiarity to the vascular ultrasound community, PSV cutpoints
      should be an important alternative to TAMM and may increase availability of
      screening and risk stratification for children with this disease. MATERIALS AND
      METHODS: Data from 1,937 baseline TCD studies from STOP were correlated with
      stroke outcome in those not treated with transfusion. Stroke prediction was
      assessed with survival analysis using TAMM, PSV and EDV as continuous variables
      individually and then pair-wise in the same model, which contained 53 stroke
      events. RESULTS: PSV and EDV were highly correlated to the TAMM velocity
      (r=0.94). The multivariate model for prediction indicated that TAMM velocity was
      a better predictor than EDV, and PSV and TAMM were approximately equivalent. PSV
      cutpoints defining the two relevant STOP risk categories--"conditional," which
      should lead to increased TCD surveillance, and "abnormal," which should lead to
      strong consideration for treatment according to STOP--were derived taking into
      consideration known differences in measurements between the dedicated Doppler
      systems (TCD) used in STOP and the transcranial Doppler imaging (TCDI) systems
      commonly used in clinical practice. The recommended PSV cutpoint for conditional
      TCD is 200 cm/s, and for abnormal TCD triggering consideration for treatment is
      250 cm/s. CONCLUSION: Assuming TCDI equipment is used and the STOP protocol is
      applied, a PSV cutpoint of 200 cm/s is recommended as the threshold for increased
      TCD surveillance (comparable to a TCD TAMM of 170 cm/s in STOP); a PSV of 250
      cm/s is recommended as the cutpoint at which, if confirmed in a second
      examination, chronic transfusion should be considered. Assuming the STOP scanning
      protocol is used, PSV is at least as good as TAMM and can be used to select
      children with SCD for treatment or increased surveillance to prevent first
      stroke.

PMID- 15517241
TI  - Open reading frame sequencing and structure-based alignment of polypeptides
      encoded by RT1-Bb, RT1-Ba, RT1-Db, and RT1-Da alleles.
AB  - MHC class II genes are major genetic components in rats developing autoimmunity.
      The majority of rat MHC class II sequencing has focused on exon 2, which forms
      the first external domain. Sequence of the complete open reading frame for rat
      MHC class II haplotypes and structure-based alignment is lacking. Herein, the
      complete open reading frame for RT1-Bbeta, RT1-Balpha, RT1-Dbeta, and RT1-Dalpha
      was sequenced from ten different rat strains, covering eight serological
      haplotypes, namely a, b, c, d, k, l, n, and u. Each serological haplotype was
      unique at the nucleotide level of the sequenced RT1-B/D region. Within individual
      genes, the number of alleles identified was seven, seven, six, and three and the
      degree of amino-acid polymorphism between allotypes for each gene was 22%, 16%,
      19%, and 0.4% for RT1-Bbeta, RT1-Balpha, RT1-Dbeta, and RT1-Dalpha, respectively.
      The extent and distribution of amino-acid polymorphism was comparable with mouse
      and human MHC class II. Structure-based alignment identified the beta65-66
      deletion, the beta84a insertion, the alpha9a insertion, and the alpha1a-1c
      insertion in RT1-B previously described for H2-A. Rat allele-specific deletions
      were found at RT1-Balpha76 and RT1-Dbeta90-92. The mature RT1-Dbeta polypeptide
      was one amino acid longer than HLA-DRB1 due to the position of the predicted
      signal peptide cleavage site. These data are important to a comprehensive
      understanding of MHC class II structure-function and for mechanistic studies of
      rat models of autoimmunity.

PMID- 15517243
TI  - Allograft rejection in the mixed cell reaction system of the demosponge Suberites
      domuncula is controlled by differential expression of apoptotic genes.
AB  - Until recently, the lack of molecular probes hampered the determination of the
      expression of pro-apoptotic and anti-apoptotic genes in sponge. In an approach to
      solve this problem, the present study describes a variety of cDNAs from the
      demosponge Suberites domuncula, coding for proteins that are characteristic for
      the initiation of apoptosis (caspase, MA3, ALG-2 protein), for the prevention of
      programmed cells death (2 Bcl-2 homology proteins, FAIM-related polypeptide, and
      DAD-1-related protein), and for morphogenetic processes (retinoid X receptor).
      They were used as probes to monitor the expression levels in vitro in the
      allogeneic mixed sponge cell reaction (MSCR) system. In the allogeneic MSCR, two
      cell aggregates (primmorphs) from genetically different animals of the same
      species were positioned next to each other. After approximately 8 days in
      culture, one of the primmorphs underwent apoptotic death, while the second
      remained alive. The expression levels of the aforementioned genes were determined
      by Northern blotting and by in situ hybridization. These experiments revealed
      that in the apoptotic primmorph, the characteristic apoptotic genes were
      expressed, while in the non-apoptotic aggregates the cell-survival genes are
      highly upregulated. Interestingly, the transcript levels of retinoid X receptor
      were higher in apoptotic primmorphs than in the non-apoptotic aggregate in the
      assay. Our data show for the first time that in the in vitro MSCR system,
      allogeneic recognition led to apoptotic cell death in one partner, while the
      other one survived. We suggest that this process is controlled by a differential
      expression of the pro-apoptotic and pro-survival genes studied here.

PMID- 15517242
TI  - Polymorphism and conservation of the genes encoding Qa1 molecules.
AB  - To evaluate the polymorphism and conservation of the major histocompatibility
      complex class Ib molecule Qa1 in wild mouse populations, we determined the
      nucleotide sequence of exons 1-3 of Qa1 of eight mouse haplotypes derived from
      wild mice, including Mus musculus domesticus, M. m. castaneus, M. m. bactrianus,
      and M. spretus, as well as two t haplotypes. Our data identify eight new alleles
      of Qa1. Taken together with previously published data on Qa1 among the common
      laboratory inbred strains, and in agreement with cytotoxic T-lymphocyte,
      serological, and biochemical data, these results further confirm the existence of
      two families of Qa1 molecules, Qa1(a)-like and Qa1(b)-like, and illuminate the
      extreme conservation of the peptide-binding region of these molecules, even
      across species.

PMID- 15517247
TI  - Biodegradation of an endocrine-disrupting chemical, di-2-ethylhexyl phthalate, by
      Bacillus subtilis No. 66.
AB  - A bacterial strain capable of rapidly degrading di-2-ethylhexyl phthalate (DEHP)
      was isolated from soil and identified as Bacillus subtilis. The organism also
      utilized di-butyl phthalate, di-ethyl phthalate, di-pentyl phthalate, di-propyl
      phthalate, and phthalic acid as sole carbon sources; and their biodegradation
      ratio was over 99%, when the incubation was performed for 5 days at 30 degrees C.
      The microorganism degraded di-2-ethylhexyl phthalate and di-butyl phthalate
      through the intermediate formation of mono-2-ethylhexyl phthalate and mono-butyl
      phthalate, which were then metabolized to phthalic acid and further by a
      protocatechuate pathway, as evidenced by oxygen uptake studies and GC-MS
      analysis. The decontamination of soil polluted with di-2-ethylhexyl phthalate by
      B. subtilis was investigated. Experimental results showed that the strain could
      degrade about 80% of 5 mM DEHP simply by adding 8% culture medium to soil,
      indicating that the degradation can occur even when other organisms are present.

PMID- 15517248
TI  - Subperiosteal ganglion associated with Paget's disease of bone.
AB  - Tumoral lesions related to Paget's disease may be classified as malignant, benign
      or pseudotumoral. While sarcomatous degeneration is the most feared complication,
      awareness of benign and pseudotumoral lesions is essential for assisting in
      accurate histological interpretation of the biopsy sample, which may avoid
      unnecessary repeat biopsies. We present the first case of a juxta-articular
      subperiosteal ganglion associated with Paget's disease, with classic imaging
      characteristics, especially on CT examination. The well-defined soft tissue mass
      at the medial aspect of the obturator rim, adjacent to a small fracture in
      pagetic quadrilateral plate, showed an ossified rim and internal gas lucencies,
      these being the hallmarks of a juxta-articular subperiosteal ganglion. On MRI,
      the lesion was of intermediate signal intensity on T1-weighted sequences,
      increased signal intensity on T2-weighted sequences, with rim enhancement after
      gadolinium contrast injection and preservation of fatty marrow signal of the
      underlying pagetic bone. Identification of the entity avoided an unnecessary
      biopsy or surgical intervention.

PMID- 15517249
TI  - Evaluation of patellar tracking in symptomatic and asymptomatic individuals by
      magnetic resonance imaging.
AB  - OBJECTIVE: To determine the patterns of patellar motion in subjects without knee
      symptoms using dynamic magnetic resonance imaging (MRI). DESIGN: Patellar
      tracking MR examinations were performed on 50 asymptomatic volunteers. The
      presence and degree of lateral subluxation and tilt of the patella was assessed
      independently by three radiologists, and discrepancies resolved by consensus.
      Using the same criteria, the tracking pattern in 50 consecutive patients,
      recently referred for imaging assessment of anterior knee pain, was studied.
      PATIENTS: Fifty volunteers (22 male, mean age 37 years) and 50 unmatched patients
      (15 male, mean age 25.5 years) were examined. RESULTS AND CONCLUSIONS: Forty-one
      per cent of a total of 97 knees in the volunteer group showed evidence of lateral
      subluxation, which was either minimal (grade 1, 32%) or minor (grade 2, 9%). No
      volunteer demonstrated major (grade 3) subluxation; lateral tilt without
      translation of the patella was also seen (2%). In the patient group, higher
      grades of lateral subluxation were more common. Minimal (grade 1) lateralization
      is a common movement pattern of the patella on knee extension, and should be
      regarded as normal.

PMID- 15517252
TI  - Small animal PET: aspects of performance assessment.
AB  - Dedicated small animal positron emission tomography (PET) systems are
      increasingly prevalent in industry (e.g. for preclinical drug development) and
      biological research. Such systems permit researchers to perform animal studies of
      a longitudinal design characterised by repeated measurements in single animals.
      With the advent of commercial systems, scanners have become readily available and
      increasingly popular. As a consequence, technical specifications are becoming
      more diverse, making scanner systems less broadly applicable. The investigator
      has, therefore, to make a decision regarding which type of scanner is most
      suitable for the intended experiments. This decision should be based on gantry
      characteristics and the physical performance. The first few steps have been taken
      towards standardisation of the assessment of performance characteristics of
      dedicated animal PET systems, though such assessment is not yet routinely
      implemented. In this review, we describe current methods of evaluation of
      physical performance parameters of small animal PET scanners. Effects of
      methodologically different approaches on the results are assessed. It is
      underscored that particular attention has to be paid to spatial resolution,
      sensitivity, scatter fraction and count rate performance. Differences in
      performance measurement methods are described with regard to commercially
      available systems, namely the Concorde MicroPET systems P4 and R4 and the quad
      HIDAC. Lastly, consequences of differences in scanner performance parameters are
      rated with respect to applications of small animal PET.

PMID- 15517257
TI  - Bridging the innate and adaptive immune responses against cancer: 95th AACR
      meeting 2004.

PMID- 15517259
TI  - Evolution of healthy thoracic aortic segment diameter during follow-up of
      patients with aortic aneurysm or dissection: a magnetic resonance imaging study.
AB  - We studied the normal evolution over time of the diameter of the healthy
      descending aorta in patients suffering from aneurysm or dissection of the
      ascending aorta, in order to anticipate potential complications of endoprosthetic
      treatment in this aortic segment. During their follow-up (average 35.9 months),
      52 patients suffering from aneurysm or dissection of the ascending aorta had 168
      aortic MRI examinations (2-7; average 3). Measurements were taken according to
      conventional reference landmarks making it possible to study the evolution of the
      diameter of the supposed healthy descending thoracic aorta. The variations in
      diameter with time were on average 5 mm, and there was no significant variation
      in this diameter, either for early controls or for the controls carried out after
      more than 1 year or 3 years, whatever the age group. Thus according to our series
      it seems that patients with a descending aorta endoprosthesis are not exposed to
      graft endoleak due to inadequate contact of the prosthesis and aorta within the 5
      years following its implantation.

PMID- 15517260
TI  - An infrarenal abdominal aortic coarctation.
AB  - We describe a case of infrarenal abdominal coarctation in a 44-year-old woman who
      presented with severe uncontrolled hypertension. She had no signs of lower limb
      ischemia with normal distal pulses. Electron beam tomography revealed abdominal
      aortic coarctation extending from the superior mesenteric artery to the inferior
      mesenteric artery with a diameter of 9 mm. Also, at the level of coarctation, the
      aortic branches including the renal arteries were in a serpentine shape.

PMID- 15517261
TI  - Orientation lesson in anatomy education.
AB  - Dissection of a human body during an anatomy course raises questions about
      invasion of privacy, cadaver sources, dying and death for medical students. The
      technical orientation in any medical education process tends to motivate students
      towards a purely biological view of the human body. An orientation lesson was
      performed, including technical instructions, with particular emphasis on how to
      deal with emotions. Two hundred and forty-two second-year students were asked to
      complete a questionnaire and two State-Trait Anxiety Inventory (STAI) self
      reports. One hundred and two students participated in an orientation lesson
      (group A) and 140 students did not (group B). Data were analyzed using SPSS. The
      t-test and chi-square test were used to evaluate differences between the groups.
      Group A students showed significantly better performance in both a verbal anatomy
      examination and multiple-choice test than group B students (p=0.001). There were
      no differences between group A and B students in the state and trait anxiety
      levels, willingness to donate their body or organs, belief in life after death,
      social activity or gender. The goal of including consideration of psychosocial
      factors in an anatomy course would allow students a thoughtful interpretation of
      their laboratory experience in the context of their professional development as
      physicians.

PMID- 15517262
TI  - Cranial sutures and craniometric points detected on MRI.
AB  - The main goal of the study was to determine on MRI the cranial sutures, the
      craniometric points and craniometric measurements, and to correlate these results
      with classical anthropometric measurements. For this purpose, we reviewed 150
      cerebral MRI examinations considered as normal (Caucasian population aged 20-49
      years). For each examination we individualized 11 craniometric landmarks
      (Glabella, Bregma, Lambda, Opisthocranion, Opisthion, Basion, Inion, Porion,
      Infra-orbital, Eurion) and three measurements. Measurements were also calculated
      independently on 498 dry crania (Microscribe 3-DX digitizer). To validate the MRI
      procedure, we measured four dry crania by MRI and with compass or digital caliper
      gauges. Cranial sutures always appeared without signal (black), whatever the MRI
      sequence used, and they are better visualized with a 5 mm slice thickness
      (compact bone overlapping). Slice dynamic analysis and multiplanar reformatting
      allowed the detection of all craniometric points, some of these being more
      difficult to detect than others (Porion, Infra-orbital). The measurements
      determined by these points were as follows: Vertex-Basion height=135.66+/-6.56
      mm; Eurion-Eurion width=141.17+/-5.19 mm; Glabella-Opisthocranion length=181.94+/
      6.40 mm. On the midline T1-weighted sagittal image, all median craniometric
      landmarks can be individualized and the Glabella-Opisthocranion length, Vertex
      Basion height and parenchyma indices can be calculated. Craniometric points and
      measurements between these points can be estimated with a standard cerebral MRI
      examination, with results that are similar to anthropometric data.

PMID- 15517263
TI  - The basis for splenic segmental dearterialization: a post-mortem study.
AB  - The anatomical features of splenic segmental vessels in 102 human spleen autopsy
      specimens were analyzed. Methods applied were corrosion casting and post-mortem
      arteriography. The superior terminal splenic branch divided extracapsularly into
      2.8+/-0.9 (range 2-5) and the inferior terminal splenic branch into 2.3+/-0.75
      (range 2-5) branches per sample. The extracapsular lengths of the segmental
      branches ranged from 4.0 to 16.7 mm and the calibers from 0.4 to 2.2 mm. Superior
      polar arteries occurred in 31.3% and inferior polar arteries in 20.6% of cases.
      Their average extracapsular lengths were 39 mm and 31 mm, respectively. In
      conclusion, segmental splenic arteries have an extrasplenic origin and course,
      with an average length and caliber that allow surgical access and ligation, in
      order to achieve segmental dearterialization for hemostasis purposes and splenic
      preservation.

PMID- 15517264
TI  - Inflammation markers and liver dysfunction.

PMID- 15517265
TI  - Analysis of HFE gene mutations (C282Y, H63D, and S65C) in the Ecuadorian
      population.
AB  - Type 1 hemochromatosis is a disorder of iron metabolism mostly related to the HFE
      gene mutations. In the present study, we performed a mutation analysis to
      determine the frequencies of the HFE gene mutations (C282Y, H63D, and S65C) in
      DNA samples of 100 healthy Ecuadorian individuals. We used the polymerase chain
      reaction (PCR) to amplify exons 2 and 4 of the HFE gene and then the restriction
      fragment length polymorphism (RFLP) method to detect the mutations. The results
      revealed that the mutations in the normal Ecuadorian population have frequencies
      of 0.0, 0.035, and 0.04 for C282Y, H63D, and S65C, respectively. We also searched
      for these mutations in 12 hemochromatosis patients, and the frequencies that we
      found were 0.0 for C282Y, 0.167 for H63D, and 0.042 for S65C. We found
      differences [using the chi-square (chi2) test] in the frequency of the H63D
      mutation between the control group and the group of hemochromatosis patients
      (p<0.01). This suggests that in Ecuador, type 1 hemochromatosis is more
      influenced by the H63D mutation than the other two mutations that we analyzed.
      Given that in a Caucasian population hereditary hemochromatosis is mostly related
      to the C282Y mutation, it is possible that the findings for the Ecuadorian
      population are due to geographical differences between the populations.

PMID- 15517266
TI  - Rituximab in the treatment of relapsed thrombotic thrombocytopenic purpura.
AB  - Several reports have defined nonfamilial thrombotic thrombocytopenic purpura
      (TTP) as an autoimmune disorder caused by antibodies to von Willebrand's factor
      cleaving protease (vWF-CP). This raises the possibility that rituximab, a
      monoclonal antibody against CD20 present in B-lymphoid cells, may have utility in
      the treatment of TTP. We report five consecutively treated patients with relapsed
      TTP who responded rapidly to immune suppression by rituximab at our institution.
      These two male and three female patients had a median age of 37 years (27-70).
      The median time from diagnosis to therapy was 24 months (8-60). Prior therapies
      included plasma exchange and corticosteroids in all cases, splenectomy (4),
      vincristine and aspirin (3), and azathioprine (2). The median number of plasma
      exchanges received prior to therapy was 59 (21-158). The cohort had a median
      platelet count of 48 x 10(9)/l (23-110), median hemoglobin of 9 g/dl (8-11), and
      median lactate dehydrogenase of 632 IU/l (311-945) prior to administration of
      rituximab. Analysis of vWF-CP activity demonstrated absent or decreased activity
      with detectable inhibitors in four patients. All patients attained a complete
      response. The median time to response after the first dose of rituximab was 5
      weeks. Responses are maintained in all patients from 10 to 21 months after
      treatment. This report adds to the evidence that rituximab has efficacy in
      nonfamilial TTP and warrants further study.

PMID- 15517267
TI  - Pure red cell aplasia with a clonal T-cell disorder.

PMID- 15517268
TI  - A phase I/II study of oral etoposide and idarubicin in elderly patients with high
      risk acute myeloid leukemia unable to undergo intensive chemotherapy.
AB  - Acute myeloid leukemia (AML) is a disease of mostly elderly patients who are
      often unable to undergo intensive intravenous chemotherapy. In an attempt to
      provide an all-oral regimen suitable for palliative treatment, we assessed the
      antileukemic efficacy of combination therapy of idarubicin 20 mg/m(2) (days 1, 3,
      and 5) and etoposide (EI) in increasing doses (75-125 mg/m(2)) on days 1-5.
      Eleven patients were included (median age 69 years, range: 56-77) with
      prognostically unfavorable characteristics (myelodysplastic syndrome, relapse, or
      unfavorable karyotypes). No complete remission and five partial remissions were
      observed whereas four patients had persistent leukemia. There were two patients
      who succumbed to early death. Median overall survival was 100 days (range: 8-493
      days). Nonhematological toxicities were acceptable with nausea/vomiting being the
      predominant side effect. Hematological toxicity with grade III/IV aplasia was
      seen in all patients. In this study EI did not show convincing antileukemic
      efficacy and was unable to induce clinically useful complete remissions, with a
      substantial risk profile. In contrast to the situation of elderly patients with
      standard-risk AML in which similar oral treatment has shown promising activity,
      EI cannot be recommended for elderly patients with high-risk AML.

PMID- 15517271
TI  - A possible mechanism for the long-lasting antitumor effect of the macromolecular
      conjugate DE-310: mediation by cellular uptake and drug release of its active
      camptothecin analog DX-8951.
AB  - DE-310, a new macromolecular prodrug, was designed to enhance the pharmacological
      profiles of a novel camptothecin analog (DX-8951f), and a single treatment with
      DE-310 exhibits a similar or greater therapeutic effect than do optimally
      scheduled multiple administrations of DX-8951f in several types of tumors. In
      this study, the drug-release mechanism by which DE-310 excites antitumor activity
      was investigated in Meth A cells, a malignant ascites model of murine
      fibrosarcoma. A single i.v. injection of DE-310 at the maximum tolerated dose
      (MTD) prolonged survival of Meth A-bearing mice by 300%. DX-8951 and glycyl-8951
      (G-DX-8951), enzymatic cleavage products of DE-310, were detected in serum and
      ascites fluid, and also in the culture medium of Meth A ascites cells incubated
      in vitro with DE-310. The total amounts of DX-8951, G-DX-8951, and conjugated DX
      8951 in Meth A tumor cells were three times higher than that in macrophages.
      Furthermore, DX-8951-related fluorescence was observed in Meth A ascites cells
      obtained from Meth A-bearing mice that had received DE-310 or CM-Dex-PA-DX-8951
      that does not release free DX-8951. DX-8951-related fluorescence was also
      observed at the site of lysosomes in cells incubated in vitro with DE-310 at 37
      degrees C, but not in those incubated at 4 degrees C. Drugs were released from DE
      310 by cysteine proteinase prepared from Meth A tumor tissue. These results
      suggest that the mechanism by which DX-8951 is released from DE-310 in vivo is
      involved in the process of uptake of DE-310 into tumor or macrophages, digestion
      by intracellular lysosomal cysteine proteinase, and subsequent secretion of the
      drugs.

PMID- 15517276
TI  - In vitro germination, protocorm formation and plantlet development of mature
      versus immature seeds from several Ophrys species (Orchidaceae).
AB  - We investigated the effect of genotype, seed maturity and culture medium on the
      in vitro germination and development of protocorms and plantlets from seeds of 13
      different Ophrys species (O. apifera, O. attica, O. cornuta, O. delfinensis, O.
      ferrum-equinum, O. lutea, O. mammosa, O. speculum, O. spruneri, O. umbilicata, O.
      argolica, O. irricolor and O. tenthredinifera) collected in Greece, some of which
      are endemic to this country. Mature seeds (10 months after collection) and
      immature seeds (2 months after anthesis) were cultured in a coconut milk-enriched
      or a pineapple-enriched medium (CEM or PEM, respectively). The highest percentage
      of callogenesis (96%) was observed in immature seeds of O. delphinensis in the
      CEM, while the highest percentage of protocorm formation (52%) was observed in
      mature seeds of O. spuneri in the CEM. Protocorm formation was significantly
      lower in immature seeds than in mature seeds in both culture media. Eventually
      almost all of the transferred protocorms developed to plantlets, which later
      formed minitubers. PEM appeared to be the most suitable for the development of
      minitubers from plantlets. All of the factors investigated--as well as their
      interactions--significantly affected callogenesis and protocorm formation. The
      results are discussed with the perspective of applying an improved protocol for
      in vitro seed germination and plantlet formation in several under-utilized Ophrys
      species.

PMID- 15517275
TI  - Efficient micropropagation of Ensete ventricosum applying meristem wounding: a
      three-step protocol.
AB  - A highly efficient three-step protocol for in vitro propagation of Ensete
      ventricosum (enset) was developed that consisted of initiation, bud
      proliferation, and shoot elongation and rooting stages. At the initiation stage,
      it was crucial to use shoot tips (5-8 mm) with subtending corm tissues as
      explants to obtain growth. The addition of 0.5-1% (w/v) activated charcoal to the
      medium was essential to prevent phenol exudation which otherwise leads to the
      loss of cultures. During the bud proliferation stage, modified MS macronutrients
      and micronutrients together with a combination of cytokinins (1.6 microM
      naphthaleneacetic acid, 4.4 microM 6-benzylaminopurine, 23.2 microM kinetin, 22.6
      microM N(6) 2-isopentyladenine) was used. This novel composition of
      macronutrients was based on the analysis of leaf nutrient content of glasshouse
      grown enset sprouts. Multiple bud formation on the enlarged corm tissue was
      induced only when the meristem region was wounded before transfer to the bud
      proliferation medium. Up to 75 healthy shoots per explant were produced, whereas
      unwounded explants produced, only one to two shoots per explant. A third stage
      with a low concentration of cytokinin enabled shoot elongation as well as root
      development. The plantlets were acclimatized with 100% success and they showed no
      apparent phenotypical deviation.

PMID- 15517277
TI  - A transmission electron microscope study of "New Dawn" climber rose (Rosa
      wichuraiana x safrano) exhibiting rose rosette disease.
AB  - The arrival of rose rosette disease (RRD) in the Washington D.C. area prompted a
      transmission electron microscope study of ultrathin sections of leaves from
      symptomatic Rosa wichuraiana x safrano plants. Virus-like particles (VLPs) or
      double membrane-bound particles (DMPs) resembling those associated with RRD in
      other types of roses, and found in several other plant diseases, were seen in the
      cytoplasm of parenchymal and vascular bundle cells and shown, for the first time,
      in guard cells and budding into the vacuoles. Contrary to previous reports,
      starch granules were found in chloroplasts of the infected cells. A presumably
      unique intramitochondrial crystal was also observed. Variations in vacuolar
      content were noted.

PMID- 15517278
TI  - Differences in the activities of some antioxidant enzymes and in H2O2 content
      during rhizogenesis and somatic embryogenesis in callus cultures of the ice
      plant.
AB  - Callus was obtained from hypocotyls of Mesembryanthemum crystallinum seedlings
      cultured on two types of medium-germination medium (GM) and callus induction
      medium (CIM). Following subculture on shoot induction medium SIM1, the callus
      formed on CIM medium regenerated roots or somatic embryos, while that obtained on
      GM medium was non-regenerative. The activities of CuZn-superoxidase dismutase
      (SOD) were comparable in all calli, but the activities of FeSOD and MnSOD varied
      according to the activity of photosystem II and the regenerative potential of the
      tissues. Catalase (CAT) activity was related to H2O2 concentration and affected
      by both the culture conditions and the morphogenic potential of the calli. The
      possible role of CAT, SODs and H2O2 in the regeneration of M. crystallinum from
      callus is discussed.

PMID- 15517279
TI  - Real time fMRI: a tool for the routine presurgical localisation of the motor
      cortex.
AB  - In patients with brain lesions adjacent to the central area, exact preoperative
      knowledge of the spatial relation of the tumour to the motor cortex is of major
      importance. Many studies have shown that functional magnetic resonance imaging
      (fMRI) is a reliable tool to identify the motor cortex. However, fMRI data
      acquisition and data processing are time-consuming procedures, and this prevents
      general routine clinical application. We report a new application of real time
      fMRI that allows immediate access to fMRI results by automatic on-line data
      processing. Prior to surgery we examined ten patients with a brain tumour
      adjacent to the central area. Three measurements were performed at a 1.5-T
      Magnetom Vision Scanner (Siemens, Forchheim, Germany) on seven patients and at a
      1.5-T Intera Scanner (Philips, Best, The Netherlands) on three patients using a
      sequential finger-tapping paradigm for motor cortex activation versus at rest
      condition. Blood oxygen level-dependant (BOLD) images were acquired using a
      multislice EPI sequence (16 slices, TE 60, TR 6000, FOV 210x210, matrix 64x64).
      The central sulcus of the left hemisphere could be clearly identified by a
      maximum of cortical activity after finger tapping of the right hand in all
      investigated patients. In eight of ten patients the right central sulcus was
      localised by a signal maximum, whereas in two patients the central sulcus could
      not be identified due to a hemiparesis in one and strong motion artefacts in the
      second patient. Finger tapping with one side versus rest condition seems to
      result in more motion artefacts, while finger tapping of the right versus the
      left hand yielded the strongest signal in the central area. Real time fMRI is a
      quick and reliable method to identify the central sulcus and has the potential to
      become a clinical tool to assess patients non-invasively before neurosurgical
      treatment.

PMID- 15517280
TI  - Respiratory lumenal change of the pharynx and trachea in normal subjects and COPD
      patients: assessment by cine-MRI.
AB  - The purpose of this study was to use cine-MRI during continuous respiration to
      measure the respiratory lumenal diameter change in the pharynx and at an upper
      tracheal level. Fifteen non-smokers and 23 chronic obstructive pulmonary disease
      (COPD) patients with smoking history (median 50 pack-years) were included. Cine
      MRI with seven frames/s was performed during continuous respiration. Minimal and
      maximal cross-sectional lumenal diameters within the pharynx and the upper
      tracheal lumen area were measured. The median diameter change in the pharynx
      (tracheal area) was 70% (1.4 cm(2)) in volunteers and 76% (1.7 cm(2)) in smokers
      (P=0.98, P=0.04). Tracheal lumenal collapse was a median of 43% in volunteers and
      64% in smokers (P=0.011). No clear disease-related difference of the pharynx
      lumen was found. The maximal cross-sectional area of the upper trachea lumen as
      well as the respiratory collapse was larger in COPD patients than in normal
      subjects. This information is important for the modelling of ventilation and
      prediction of drug deposition, which are influenced by the airway diameter.

PMID- 15517281
TI  - The role of imaging techniques in renal transplantation.
AB  - Our aim is to review the utility of the different imaging techniques in the field
      of renal transplantation (RT). A total of 500 potential RT recipients have been
      evaluated and were included in the waiting list. From 1978 to 2003, a total of
      900 RT recipients were clinically followed-up and different imaging techniques
      assessed. The main indications for the different techniques were: (1) MR
      angiography to establish the vascular anatomy of the living donor with 95%
      accuracy for the detection of multiple renal vessels. (2) Abdominal ultrasound of
      the donor in order to detect lithiasis, incidental renal tumors or anatomic
      anomalies. (3) Vascular evaluation of the recipients was essential considering
      the aging character of this population. X-ray film of the abdomen was a routine
      technique. Doppler ultrasound (DOP-US) of the iliac vessels and an angiographic
      study (DSA, CT, MR) of the iliac and splenic arteries were indicated only in
      selected cases. (4) DOP-US was useful in the diagnosis of graft dysfunction after
      RT. It allowed the exclusion of thrombosis and urinary obstruction, and was
      useful to distinguish between acute tubular necrosis, cyclosporine nephrotoxicity
      and acute rejection (AR). (5) Finally, ultrasound was used as a percutaneous
      approach to pyelocaliceal systems of grafts affected by ureteral stenosis or
      fistula and for draining fluid collections after RT (lymphocele, abscess,
      hematoma or urinoma).

PMID- 15517282
TI  - Glucocorticoid receptors are involved in the regulation of pulsatile urea
      excretion in toadfish.
AB  - The objectives of this study were to characterize the pattern of pulsatile urea
      excretion in the gulf toadfish in the wake of exogenous cortisol loading and to
      determine the receptors involved in the regulation of this mechanism. Toadfish
      were fitted with indwelling arterial catheters and were infused with isosmotic
      NaCl for 48 h after which fish were treated with cortisol alone, cortisol +
      peanut oil, cortisol + RU486 (a glucocorticoid receptor antagonist) or cortisol +
      spironolactone (a mineralocorticoid receptor antagonist). Upon cortisol loading,
      fish treated with cortisol alone, cortisol + oil or cortisol + spironolactone
      experienced a two- to threefold reduction in pulsatile urea excretion. This
      reduction was due to a decrease in urea pulse size with no effect on pulse
      frequency compared to values measured during the control NaCl infusion period. In
      addition, these fish showed an increase in plasma urea concentrations upon
      treatment. These apparent effects of cortisol treatment were abolished in fish
      treated with cortisol + RU486. In contrast, these fish showed an increase in
      pulsatile urea excretion mediated by a twofold increase in pulse size with no
      change in frequency. Likewise, fish treated with cortisol + RU486 showed a
      significant decrease in plasma urea concentrations over the course of the
      experiment. The findings of this study indicate that high levels of cortisol
      reduce pulsatile urea excretion by decreasing pulse size. In addition, it appears
      that glucocorticoid receptors and not mineralocorticoid receptors are involved in
      the regulation of the toadfish pulsatile urea excretion mechanism.

PMID- 15517283
TI  - Fat-cell mass, serum leptin and adiponectin changes during weight gain and loss
      in yellow-bellied marmots (Marmota flaviventris).
AB  - Leptin and adiponectin are proteins produced and secreted from white adipose
      tissue and are important regulators of energy balance and insulin sensitivity.
      Seasonal changes in leptin and adiponectin have not been investigated in
      mammalian hibernators in relationship to changes in fat cell and fat mass. We
      sought to determine the relationship between serum leptin and adiponectin levels
      with seasonal changes in lipid mass. We collected serum and tissue samples from
      marmots (Marmota flaviventris) in different seasons while measuring changes in
      fat mass, including fat-cell size. We found that leptin is positively associated
      with increasing fat mass and fat-cell size, while adiponectin is negatively
      associated with increasing lipid mass. These findings are consistent with the
      putative roles of these adipokines: leptin increases with fat mass and is
      involved in enhancing lipid oxidation while adiponectin appears to be higher in
      summer when hepatic insulin sensitivity should be maintained since the animals
      are eating. Our data suggest that during autumn/winter animals have switched from
      a lipogenic condition to a lipolytic state, which may include leptin resistance.

PMID- 15517284
TI  - The viscosity and glycoprotein biochemistry of salmonid mucus varies with
      species, salinity and the presence of amoebic gill disease.
AB  - Fish mucus has previously been reported to change in appearance and composition
      among species and in response to changes in salinity and disease status. This
      study reports on the mucus viscosity and glycoprotein biochemistry of Atlantic
      salmon (Salmo salar L.), brown trout (Salmo trutta L.) and rainbow trout
      (Oncorhynchus mykiss Walbaum) in freshwater and seawater, both naive to and
      affected by amoebic gill disease (AGD). Cutaneous mucus viscosity was measured
      over a range of shear rates (11.5, 23, 46 and 115 s(-1)), and non-Newtonian
      behaviour was demonstrated for all three species. Mucus viscosity was
      significantly greater in seawater than in freshwater for all species, and
      significantly lower in AGD-affected Atlantic salmon and brown trout. Mucus
      glucose, total protein and osmolality data indicated that differences in
      viscosity due to salinity were mostly attributed to changes in mucus hydration,
      while differences due to disease were mostly attributed to changes in mucus
      composition. Trends in gill mucus cell histochemistry included shifts in
      glycoproteins from neutral mucins in freshwater to acidic mucins in seawater, and
      shifts towards neutral mucins, with an increase in mucus cell numbers, in
      response to AGD. Results suggested that Atlantic salmon and brown trout are more
      similar to one another in their mucus profile than to rainbow trout. Atlantic
      salmon and brown trout both exhibited a whole-body mucus response to AGD, whereas
      rainbow trout exhibited only a local gill response. Findings hold implications
      for fish physiology and pathology, and indicate that future fish-disease
      management strategies should be species and condition specific.

PMID- 15517285
TI  - Cold tolerance of Littorinidae from southern Africa: intertidal snails are not
      constrained to freeze tolerance.
AB  - All intertidal gastropods for which cold tolerance strategies have been assessed
      have been shown to be freeze tolerant. Thus, freeze tolerance is considered an
      adaptation to the intertidal environment. We investigated the cold tolerance
      strategies of three species of subtropical and temperate snails (Gastropoda:
      Littorinidae) to determine whether this group is phylogenetically constrained to
      freeze tolerance. We exposed 'dry' acclimated and 'wet' rehydrated snails to low
      temperatures to determine temperature of crystallisation (Tc), lower lethal
      temperature and LT(50) and to examine the relationship between ice formation and
      mortality. Tc was lowest in dry Afrolittorina knysnaensis (-13.6+/-0.4 degrees
      C), followed by dry Echinolittorina natalensis (-10.9+/-0.2 degrees C) and wet A.
      knysnaensis (-10.2+/-0.2 degrees C) . The Tc of both A. knysnaensis and E.
      natalensis increased with rehydration, whereas Tc of dry and wet Afrolittorina
      africana did not differ (-9.6+/-0.2 and -9.0+/-0.2 degrees C respectively). Wet
      snails of all species exhibited no or low survival of inoculative freezing,
      whereas dry individuals of A. knysnaensis could survive subzero temperatures
      above -8 degrees C when freezing was inoculated with ice . In the absence of
      external ice, Afrolittorina knysnaensis employs a freeze-avoidance strategy of
      cold tolerance, the first time this has been reported for an intertidal snail,
      indicating that there is no family-level phylogenetic constraint to freeze
      tolerance. Echinolittorina natalensis and A. africana both showed pre-freeze
      mortality and survival of some internal ice formation, but were not cold hardy in
      any strict sense.

PMID- 15517286
TI  - Chylous ascites following liver resection--case report.
AB  - Chylous ascites is an intraperitoneal collection of fluid that appears milky
      because of the presence of unusual amounts of fat. It is a result of
      interference, interruption, or obstruction of lymph flow through chyle
      transporting vessels, and remains rare as a complication of surgical
      intervention. Liver resection has been infrequently reported as a cause of
      chylous ascites. We report a case of chylous ascites developing after laparotomy
      and right lobe liver resection, which was diagnosed early and managed
      conservatively with minimal morbidity. The key lies in awareness of the
      condition, early diagnosis, and aggressive management with nutritional support.

PMID- 15517287
TI  - Isolated liver tuberculosis: a case report.
AB  - A case of liver tuberculosis resembling a hemangioendothelioma on computed
      tomography and clinically masquerading as a tumor is reported. The cause of
      isolated liver tuberculosis and the importance of an open liver biopsy is
      discussed, with a review of the literature.

PMID- 15517288
TI  - Paediatric priapism--treatment conundrum.
AB  - Priapism is a rare condition in childhood. The majority of reported cases are
      boys with sickle cell disease, in whom nonoperative management may be successful
      when patients present early. We report a 14-year-old boy with sickle cell disease
      who presented with priapism of 72-h duration and was successfully treated by
      bilateral saphenocorporal shunts.

PMID- 15517289
TI  - "Pouch colon patch graft"--an alternative treatment for congenital short colon.
AB  - A patch graft of the pouch colon over the pulled-through ileum in a patient with
      long-length pouch colon (in whom the entire colon was replaced by a pouch that
      communicated with the urinary bladder) was tried with good results for the first
      time. At follow-up the patient was found to have normal bowel patterns and weight
      gain. Though colon patch grafts have been widely used in patients with total
      colonic aganglionosis, they have not been tried for the short colon. The authors
      discuss the clinical setting in which the procedure may prove useful in patients
      with pouch colon and why these patch grafts may yield comparable or even better
      results in patients with pouch colon compared with those with total colonic
      aganglionosis.

PMID- 15517291
TI  - Evaluation of neonates with esophageal atresia using chest CT scan.
AB  - Recent literature stresses various factors that influence outcome in neonates
      with esophageal atresia (EA), including associated congenital anomalies,
      ventilator dependency, and gap length. Although the existing modalities can
      fairly accurately assess the first two factors, a comparable modality for
      assessing the interpouch gap in a natural unstretched position preoperatively is
      lacking. A technique of direct sagittal computed tomography (CT) scanning of the
      chest, initially employed by Tam et al. in 1987, was found to provide fairly
      accurate information on the level of origin of the fistula and the interpouch
      distance, with pouches in natural, unstretched positions, in two neonates with EA
      and distal tracheoesophageal fistula (TEF). However, no further studies were
      reported using this technique. We studied 10 neonates with EA and distal TEF, the
      most common variant, using this technique. The addition of axial cuts was done in
      the event of a short upper pouch or suboptimally-clear anatomical details in
      sagittal chest CT films. The preoperative information in our study subjects was
      found to corroborate well with operative findings except in the one patient with
      laryngotracheoesophageal cleft (LTEC). Prior information of a left
      bronchoesophageal fistula in two of the neonates with dextrocardia greatly helped
      us in saving operative time and difficulties and postoperative hassles. The chest
      CT scan proved to be a noninvasive and quick means for investigating neonates
      with the most common variant of EA. CT scanning could be extended for routine
      preoperative evaluation of neonates with EA to prepare for intraoperative
      problems, besides helping prognostication.

PMID- 15517290
TI  - Feasibility of perineal sagittal approaches in patients without anorectal
      malformations.
AB  - Perineal sagittal approaches (posterior sagittal anorectoplasty and anterior and
      posterior sagittal transanorectal approaches) allow complete anatomic exposure of
      the perineum and lower pelvis. Moreover, they reduce the risk of damaging
      important structures because the incision is led in the midline. Therefore, many
      surgeons have used these approaches to treat diseases other than anorectal
      malformations (ARM), including intestinal dysganglionosis, trauma,
      pseudohermaphroditism, presacral mass, and rectal duplication. The aim of this
      study was to describe a small series of patients operated on via these approaches
      at Gaslini Children's Hospital over a 5-year period. We retrospectively evaluated
      10 patients consecutively operated on via a perineal sagittal approach, with or
      without sphincteric structure involvement, between January 1997 and December
      2001. All of these patients were without ARM. Indications included retrorectal
      abscesses (two), iatrogenic anal canal stenosis (one), postinflammatory anal
      canal stenosis (one), internal anal sphincter neurogenic achalasia (one), female
      pseudohermaphroditism (one), benign sacrococcygeal teratomas (two), malignant
      sacrococcygeal teratoma (one), and perineal rhabdomyosarcoma (one). Protective
      colostomy was used in four patients. The parameters that we analysed included
      technical details, possible complications, perineal cosmetic appearance, and
      outcome. No complications were experienced. The postoperative cosmetic perineal
      appearance was excellent in all patients, and continence, when assessed, was
      always considered satisfactory. All tumours underwent complete gross resection.
      However, one patient with malignant sacrococcygeal teratoma died as a result of
      the malignant process 2 years after surgery. Although our study was carried out
      on a small series of patients, it confirmed that perineal sagittal approaches can
      be used not only for ARM but also for other conditions involving perirectal
      pouches, presacral space, and urogenital structures, as these approaches are safe
      and provide excellent cosmetic results as well as satisfactory functional
      outcome. Although tumours can be treated via these approaches, outcome remains
      related to the nature and malignancy of the disease itself.

PMID- 15517292
TI  - Incidence of cryptorchidism and ascending testes in trisomy 21: a 10 year
      retrospective review.
AB  - Children with Down syndrome have an increased risk of cryptorchidism, but the
      reported incidence is unclear. In a proportion of these children, the testes are
      within the scrotum at birth but later appear to have ascended to an ectopic
      position. Records of patients diagnosed with trisomy 21 who had surgery for
      undescended testes in two tertiary paediatric centres over a 10-year period were
      examined. Information on liveborn males with Down syndrome was obtained from the
      Victorian Genetic Registry, and then the incidence of congenital and acquired
      undescended testes was determined. The incidence of undescended testes in Down
      syndrome was found to be 6.52% (24/368), with 4.35% (16/368) being acquired
      undescended or ascending testes. In conclusion, there is an increased incidence
      of cryptorchidism in Down syndrome; in particular, there is a significant
      proportion of acquired undescended testes.

PMID- 15517293
TI  - Topography, stem cell behaviour, and organogenesis.
AB  - The fundamental problem of development is to explain how the progeny of a single
      cell, the fertilised egg, differentiates to form all the tissues of the body in
      the right place at the right time. It has only been during the last couple of
      years that the mechanisms and molecules mediating interactions between cells and
      tissues have begun to be delineated. This article reviews some of these recent
      studies. Sequences of topographically defined cellular interactions lead not only
      to the development of the body but also to the obvious and remarkable inference
      that the body more or less automatically builds itself.

PMID- 15517296
TI  - [Methodologic aspects of public health economy].

PMID- 15517294
TI  - Genetics and developmental biology of oesophageal atresia and tracheo-oesophageal
      fistula: lessons from mice relevant for paediatric surgeons.
AB  - Oesophageal atresia and tracheo-oesophageal fistula are relatively frequently
      occurring foregut malformations of which the aetiology and pathogenesis are
      poorly understood. Recent results of molecular genetic studies, in particular the
      use of single and compound mutant mice, have yielded a tremendous increase in the
      understanding of the molecular mechanisms involved in normal and abnormal foregut
      morphogenesis. In the introduction of this paper, we review the very early stages
      of normal and abnormal embryology of the foregut derivatives and the separation
      of the foregut into a ventral respiratory part and a dorsal digestive part. After
      that, we describe the genes that have been demonstrated to play an important role
      in these processes.

PMID- 15517297
TI  - [Conceptual and methodological basics of cost assessments in rheumatology].
AB  - Cost-of-illness studies in rheumatic conditions show an enormous variability in
      reported costs. Reasons are-among others-a lack of standardization with regards
      to relevant cost domains and the utilization of various insufficiently validated
      costing sources. A flow scheme is presented which may serve as a systematic basis
      for a valid costing analysis. The scheme includes: i) Selection of relevant cost
      domains. A comprehensive matrix of cost domains may be used as a framework.
      According to the specific aims of any costing study individual domains might be
      selected. ii) An adequate level of detail has to be determined taking into
      account factors such as the validity of the data collection and the feasibility.
      iii) Appropriate objective (i. e. usage of administrative data) or subjective (i.
      e. patient-derived) data sources have to be identified under consideration of
      respective strengths and weaknesses. While administrative sources provide a valid
      access to costing data accessibility and feasibility are important advantages of
      patient-derived costing procedures. iv) During data collection the potential bias
      due to protocol-driven costs and the differentiation of disease-related from
      other health care costs should be considered. v) The data analysis should support
      a transparent presentation of the costing data both in physical and monetary
      units. In summary, no 'gold standard' has been established for costing studies
      yet. However, valid costing approaches might follow the flow scheme presented in
      this analysis.

PMID- 15517298
TI  - [The role of utilities in economic evaluations of healthcare interventions-an
      introduction].
AB  - Assessment of strength of preference values (utilities) for patients' own health,
      or disease states from a societal perspective, is an essential element to
      economic evaluations of healthcare interventions. This review provides an
      overview of the different methods used to directly elicit strength of preference
      values: the standard gamble, time trade-off and rating scale methods. Methods
      used to derive utilities for patients' health states indirectly, and from a
      societal perspective are described. Three commonly used questionnaires: Health
      Utilities Index 3, EQ-5D and SF-6D are briefly commented upon. We also discuss
      the usefulness of utilities and advantages and disadvantages to be considered
      when choosing direct or indirect utility elicitation methods.

PMID- 15517299
TI  - [Mid-term results of autologous chondrocyte transplantation in knee and ankle. A
      one- to six-year follow-up study].
AB  - BACKGROUND: The reimplantation of autologous chondrocytes is a new technique in
      reconstruction of cartilage defects; initial results achieved with this technique
      have been promising. In an arthroscopic procedure, scales of cartilage are
      obtained from intact cartilage. The chondrocytes are then multiplied in special
      laboratories. A few weeks later, in a second procedure, the cartilage defect is
      filled with the cell suspension and closed with a flap of periosteum. METHOD: At
      our department, autologous chondrocyte transplantation (ACT) has been used in 10
      patients since 1996, in 6 cases in the knee joint, and in 4 cases in the ankle
      joint. The mean age of the patients was 30 years. The mean size of the defect was
      4 cm(2). In 4 patients, a parallel surgical procedure was required at the time of
      removal. RESULTS: The mean duration of follow-up was 21/2 years. Six patients had
      good to excellent results, 3 patients had moderate results, and one patient a
      poor result. The modified Cincinnati rating scale was improved from 2.4 to 7.1
      points, and the Lysholm score from 59.2 to 86.6 points. The AOFAS score for ankle
      joints had improved from 33 to 76. CONCLUSION: We were able to show that ACT
      achieves improvement in the knee as well as ankle joint in the majority of
      patients. ACT appears to be a promising therapeutic concept for both joints.

PMID- 15517300
TI  - [Measurement of quality of life in patients with active ankylosing spondylitis
      being treated with infliximab-a comparison of SF-36 and SF-12].
AB  - BACKGROUND: Quality of life as a part of the WHO definition of health is an
      important assessment tool for measuring the success in the treatment of chronic
      diseases. The short form 36 questionnaire (SF-36), which is measuring health
      related quality of life, was used in a multicentre placebo controlled study in
      patients with ankylosing spondylitis (AS) treated with the anti-TNF-alpha
      antibody infliximab. As previously reported, substantial changes of almost all
      outcome parameters were observed in this study because of the substantial
      clinical improvement that is known to occur in most patients treated with anti
      TNF agents. The short form 12 questionnaire (SF-12) is shorter and quicker to
      complete as the SF-36. The summary scales of both questionnaires were compared in
      this study to answer the question whether the SF-12 can also be used in AS
      patient populations without too much loss of information. Using the shorter from
      could be an advantage for further studies in patients with AS, for example, the
      inception cohort for spondyloarthritides within the German Network of competence
      in rheumatology. Furthermore the data can be compared to the German standard
      population. METHODS: In this multicentre placebo controlled study 70 patients
      with active disease were enrolled: 35 AS patients received placebo, 35 were
      treated with infliximab, 5 mg/kg at week 0/2/6. Thereafter all patients were
      treated in an open study with infliximab at 5 mg/kg every 6 weeks. The disease
      activity (BASDAI), function (BASFI), mobility (BASMI), pain (NRS) and CRP as well
      as SF-36 were assessed. Data to calculate the SF-12 were extracted from the SF-36
      questions and compared concerning agreement of individual levels, correlation
      with each other and with the BASFI, sensitivity to change and missing values.
      RESULTS: All outcome parameters for disease activity as well as all subscales of
      health related quality of life improved in patients with active AS treated with
      infliximab. The comparability of the sum components for SF-12 and SF-36 were high
      (physical health r=0.912 and mental health r=0.957). CONCLUSION: These data
      suggest that the shorter version of the SF-36, the SF-12, is capable to measure
      quality of life in clinical studies with AS patients.

PMID- 15517301
TI  - [Value of inpatient care in rheumatoid arthritis-an evidence based report].
AB  - Our aim was to analyze the existing body of evidence about inpatient care of
      patients suffering from rheumatoid arthritis (RA). The report was induced by the
      executive board of the German Society of Rheumatology which assigned the "Oliver
      Sangha committee" to dissect and point out the tasks of inpatient care during the
      next few years. A systemic search of the literature was performed covering the
      years 1966 to 2001. A total of 16 studies were selected and thoroughly appraised
      in a systematic way. Four randomized controlled trials addressing the question
      could be identified. All of them included only patients in a clinical condition
      allowing outpatient care as well. Two studies indicate some advantage of
      inpatient care in comparison to outpatient treatment. Two studies, both
      equivalence studies from design, reveal that RA patients do not generally
      experience additional benefit from hospitalization. Consideration of two
      additional cohort studies demonstrates the increased need of inpatient care in RA
      patients. None of the studies was derived from the German health care system.
      Emergency cases were not the subject of any of these trials. General statements
      about the value of inpatient care of RA patients can not be drawn from the
      analyzed studies. The committee makes suggestions for future investigations that
      may help to answer this important question considering the special circumstances
      of the German health care system.

PMID- 15517302
TI  - [Out-of-pocket medical spending for care in patients with recent onset rheumatoid
      arthritis].
AB  - We examined out-of-pocket medical expenditures (OoP) of 869 patients with recent
      onset rheumatoid arthritis (ACR criteria, disease duration <2 years) using data
      from a prospective observational cohort. Out-of-pocket costs were retrospectively
      assessed for a period of 6 months by a list of 14 cost domains. Of the patients,
      82% had costs due to copayments for prescribed drugs and 56% for over-the-counter
      drugs. Within six months each patient spent an average of 47 (+/- 67) Euro as co
      payment and 45 (+/- 96) Euro for over-the-counter drugs. A comparable sum was
      spent for complementary and alternative medicine (47+/-250 Euro), which was used
      by 14% of the patients. The mean total OoP expenditure caused by RA was 628 Euro
      p.a. (median 306, IQ 66-334 Euro). The median costs accounted for approximately
      2% of the average disposable yearly income in Germany. Out-of-pocket spending
      increased with functional limitations, poor health condition and pain as well as
      with level of education. A multivariate logistical regression analysis showed
      that patients with these characteristics spent about twice as much as patients
      with mild disease or low educational level. The odds ratios for having more than
      306 Euro OoP-costs p.a. were OR=2.6 (CI 1.7-4) for patients with severe vs.
      moderate functional disability (HAQ> or =1.5 vs <1.5), OR=2.4 (CI 1.4-4.4) for
      patients in poor vs. good health condition (NRS 7-10 vs 0-3), and OR=2.1 for
      patients with severe vs. mild pain (CI 1.4-3.3). The level of OoP spending also
      varied by employment status (OR=0.28; CI 0.1-0.6 for jobless vs employed
      patients). Despite almost universal insurance coverage in Germany, patients with
      rheumatoid arthritis were exposed to substantial OoP expenditures. As
      policymakers discuss cost sharing and design of benefit packages to contain
      health spending, it is important to consider the expenditures that persons with
      chronic conditions like rheumatoid arthritis already have.

PMID- 15517304
TI  - [EURORITS: rheumatology education in Europe under scrutiny. Preliminary results
      of a European survey].

PMID- 15517303
TI  - [Panzytopenia from combination therapy with azathioprin and allopurinol].
AB  - Azathioprine has been used in rheumatology for more than twenty years.
      Indications are collagen diseases with multiorgan involvement, where co
      medications are frequently necessary. We describe a patient suffering from
      pancytopenia following a combination therapy of azathioprine and allopurinol
      because of lupus erythematodes and diabetic nephropathy with hyperuricemia.

PMID- 15517305
TI  - [A. J. Landre-Beauvais (1772-1840)--the actual first description of rheumatoid
      arthritis].

PMID- 15517308
TI  - Effects of a tryptic hydrolysate from bovine milk alphaS1-casein on hemodynamic
      responses in healthy human volunteers facing successive mental and physical
      stress situations.
AB  - BACKGROUND: Preclinical results in rats have demonstrated anxiolytic-like effects
      of a tryptic bovine alphaS1-casein hydrolysate. AIM OF THE STUDY: We investigated
      the putative effects of this tryptic hydrolysate on systolic (SBP), diastolic
      (DBP) blood pressures, heart rate (HR) values and plasma cortisol concentrations
      (CC) in human healthy volunteers facing successive stress situations. METHODS:
      The subjects were (double blind) randomly allocated to ingest three times, 12
      hours apart, two capsules containing either 200 mg of alphaS1-casein hydrolysate
      (TS) or bovine skimmed milk powder as a placebo (CS). On the morning of the test
      day, a first blood sample for baseline measurement of CC was taken before the
      subjects were submitted to the Stroop test (ST) and, after a 30-min rest, to a
      Cold Pressor test (CPT). SBP, DBP, and HR were continuously recorded for 5 min
      before the ST and during each stress situation. A second blood sample was taken
      15 min after the end of the CPT condition. RESULTS: ST and ST + CPT combined test
      situations increased SBP, DBP and HR. The significant "Treatment x SBP" and
      "Treatment x DBP" interactions indicated the lower percentage changes in SBP and
      DBP of the TS. In addition, the results showed a significant decrease of the CC
      in the TS but not in the CS throughout the ST + CPT combined stress tests. HR
      remained stable in TS between the initial rest period and the CPT unlike what
      happened in CS. CONCLUSION: On the basis of blood pressure and cortisol changes,
      these results suggest an antistress profile of this alphaS1-casein hydrolysate in
      human subjects.

PMID- 15517309
TI  - Mutation analysis of the Ras pathway genes NRAS, HRAS, KRAS and BRAF in
      glioblastomas.
AB  - Aberrant activation of Ras signaling is a common finding in human glioblastomas.
      To determine the contribution of Ras gene mutations to this aberration, we
      screened 94 glioblastomas for mutations in the three Ras family genes NRAS, KRAS
      and HRAS. All tumors were additionally analyzed for mutations in BRAF, which
      encodes a Ras-regulated serine/threonine kinase with oncogenic properties.
      Mutation analysis of the entire coding regions of NRAS and KRAS, as well as the
      known mutation hot-spot sites in HRAS, identified somatic point mutations in two
      glioblastomas, both affecting codon 12 of NRAS (c.35G>A, p.G12D). Three
      additional tumors carried BRAF mutations altering the known hot-spot codon 599
      (c.1796T>A, p.V599E). None of these five glioblastomas showed amplification of
      the EGFR or PDGFRA genes, while three of the tumors, including two with NRAS and
      one with BRAF mutation, demonstrated PTEN missense mutations or loss of PTEN mRNA
      expression. Taken together, our data suggest activating mutations in NRAS or BRAF
      as a molecular alteration that contributes to aberrant Ras signaling in a small
      fraction of glioblastomas.

PMID- 15517310
TI  - Human cerebral infarct: a proposed histopathologic classification based on 137
      cases.
AB  - We studied the microscopic features of 137 cases of human cerebral infarct. In
      each case, the age of the lesion was determined by measuring the time elapsed
      between initial clinical presentation and date of surgery or death. Multiple
      microscopic variables were analyzed on hematoxylin and eosin-stained sections.
      There were 104 (76%) male and 33 (24%) female patients with a median age of 64
      years. The location of the infarcts included 129 cerebral, 5 cerebellar, and 1
      each in the pons, midbrain and medulla. The age of the lesions ranged from 1 day
      to 53 years. All lesions were single and varied from lacunes to large infarcts in
      the distribution of one or more cerebral arteries. Key histologic features of the
      proposed classification are as follows: (1) phase of acute neuronal injury (11
      cases studied), age 1-2 days, characterized by the presence of neuronal changes,
      and spongiosis of the neuropil and absence of neuronal ferrugination, chronic
      inflammation, macrophages, neo-vascularization and cavitation; (2) phase of
      organization subdivided into: (a) phase of acute inflammation (31 cases), age 3
      37 days, characterized by coagulative necrosis, and frequent acute inflammation,
      and (b) phase of chronic inflammation (57 cases), age 10 days-53 years,
      characterized by the presence or absence of coagulative necrosis, neuronal
      injury, red neurons, macrophages, mononuclear inflammatory cells, perivascular
      cuffing, cavitation, gliosis, spheroids; absence of neutrophils; and (3) phase of
      resorption (38 cases), age 26 days-23 years, characterized by absence of an
      inflammatory response. Neuronophagia is not a feature of cerebral infarcts.

PMID- 15517312
TI  - Aquaporin-4 is increased in the sclerotic hippocampus in human temporal lobe
      epilepsy.
AB  - The hippocampus of patients with mesial temporal lobe epilepsy is often hardened
      and shrunken, a condition known as sclerosis. Magnetic resonance imaging reveals
      an increase in the T2-weighted signal, while diffusion weighted imaging shows a
      higher apparent diffusion coefficient in sclerotic hippocampi, indicating
      increased water content. As water transport appears to be coupled to K+ clearance
      and neuronal excitability [4], the molecular basis of the perturbed water
      homeostasis in the sclerotic hippocampus was explored. The expression of
      aquaporin-4 (AQP-4), the predominant water channel in the brain, was studied with
      quantitative real time PCR analysis, light microscopic immunohistochemistry and
      high-resolution immunogold labeling. A significant increase in AQP-4 was observed
      in sclerotic, but not in non-sclerotic, hippocampi obtained from patients with
      medically intractable temporal lobe epilepsy. This increase was positively
      correlated with an increase in the astrocyte marker glial fibrillary acidic
      protein. AQP-4 was localized to the plasma membranes of astrocytes including the
      perivascular end-feet. Gene expression associated with increased AQP-4 was
      evaluated by high throughput gene expression analysis using Affymetrix GeneChip
      U133A and related gene networks were investigated with Ingenuity Pathways
      Analysis. AQP-4 expression was associated with a decrease in expression of the
      dystrophin gene, a protein implicated in the anchoring of AQP-4 in perivascular
      endfeet. The decreased expression of dystrophin may indicate a loss of polarity
      in the distribution of AQP-4 in astrocytes. We conclude that the perturbed
      expression of AQP-4 and dystrophin may be one factor underlying the loss of ion
      and water homeostasis in the sclerotic hippocampus and hypothesize that the
      reported changes may contribute to the epileptogenic properties of the sclerotic
      tissue.

PMID- 15517313
TI  - Management of intra-articular fractures of the proximal interphalangeal joint by
      internal fixation and bone grafting.
AB  - INTRODUCTION: Intra-articular fractures of the proximal interphalangeal joint are
      usually treated by one of many methods of external fixation, but this does not
      restore the articular surface. We describe a procedure where bone grafting and
      internal fixation are used to restore the articular surface. PATIENTS AND
      METHODS: A prospective study was conducted in which three patients underwent
      surgical treatment for this fracture. We describe a surgical procedure where bone
      graft harvested from the distal radius is packed through a diaphyseal window to
      restore the articular surface. This is followed by internal fixation with mini
      screws. RESULTS: The average follow-up was 61 months. At last follow-up the
      average arc of movement of the proximal interphalangeal joint was 100 deg and the
      average Disability of the Arm, Shoulder and Hand (DASH) Score was 2.
      Postoperative radiographs showed restoration of the articular contour in all
      three patients. CONCLUSION: The surgical technique described addresses the issues
      of restoration of the articular surface and permits early mobilisation. The
      results for our group are excellent and compare favourably with those achieved
      using external fixators described in the literature.

PMID- 15517315
TI  - The influence of preclinical anaemia on outcome following total hip replacement.
AB  - INTRODUCTION: Preoperative anaemia confers a higher intraoperative and
      postoperative risk of complications on a patient. Preclinical anaemia is defined
      as a patient with laboratory indices of anaemia but without any of the symptoms.
      The patient population who undergo total hip replacement (THR) are elderly and
      are more likely to fall into this category. Our aim was to assess the effect of
      preclinical anaemia on a patient's postoperative course. MATERIALS AND METHODS: A
      prospective analysis of elective THRs performed over a 10-month period was
      carried out. Preoperative haematological indices were recorded and correlated
      with postoperative complication rates. RESULTS: A total of 225 elective THRs were
      included in the study. Patients with preclinical anaemia on admission had a
      higher incidence of postoperative infection and transfusion (p<0.001) and a
      longer postoperative inpatient stay. Preoperative iron supplementation in
      patients with preclinical iron deficiency anaemia resulted in a reduction in
      transfusion requirements (p=0.00125). CONCLUSIONS: Identification and treatment
      of patients with preclinical anaemia preoperatively may reduce postoperative
      infection and transfusion needs and result in a shorter inpatient stay.

PMID- 15517317
TI  - Clinical outcomes in the revision of unicondylar arthoplasties to bicondylar
      arthroplasties. A matched-pair study.
AB  - INTRODUCTION: The aim of the following study was to find out how much a
      previously implanted unicondylar prosthesis affects the clinical and functional
      outcome of a total knee arthroplasty in case of revision surgery. MATERIALS AND
      METHODS: A matched-pair comparative analysis was performed on 28 patients (group
      A) who required bicondylar knee arthroplasty following failed unicondylar
      arthroplasty and 28 patients (group B) with primary bicondylar knee arthroplasty.
      Both groups were matched according to age, sex, weight, height, type of
      prosthesis, and follow-up time after bicondylar arthroplasty. The patients'
      evaluation was based on the Knee Society Score and the WOMAC Score. Radiographs
      (AP weight-bearing and lateral) were taken of the knee. The average follow-up
      time after bicondylar arthroplasty was 55+/-15 months in group A and 56+/-13
      months in group B. RESULTS: The knee score was 71.8+/-18 and 80.4+/-10 points
      (p=0.01) and the function score 56.1+/-15 and 64.1+/-19 points (p=0.1) for group
      A and group B, respectively. The subjective assessment according to the WOMAC
      Score was statistically significant in terms of the functional outcome. Increased
      postoperative range of motion of 109 degrees +/-11 degrees was noticed for group
      B in comparison with group A (101 degrees +/-8 degrees ; p=0.004). Patients
      revised from an unicondylar arthroplasty required a significantly thicker
      polyethylene inlay (12.9+/-3 mm) compared with the primarily implanted group
      (10.3+/-3 mm; p=0.004). CONCLUSION: Revision of an unicondylar to a bicondylar
      knee replacement showed inferior functional results in comparison to primary
      bicondylar knee arthroplasty. Patients are satisfied after conversion of an
      unicondylar to bicondylar prosthesis, but not quite as much as patients who
      received a primary bicondylar arthroplasty. However, in the small number of
      patients where revision surgery after failed unicondylar prosthesis is required,
      the patient had already been successfully treated for many years.

PMID- 15517318
TI  - Iliopsoas bursitis following total hip replacement.
AB  - We report the imaging features of a 52-year-old man presenting with a groin mass
      and gross lower limb oedema secondary to venous occlusion by massive cystic
      enlargement of the iliopsoas bursa 4 years after uncemented primary total hip
      replacement. Ultrasonography of the groin mass demonstrated a large cystic lesion
      extending into the pelvis. CT showed displacement of the external iliac vessels
      with venous compression. Bursography showed the bursa's margins and no
      communication with the hip joint. Diagnostic aspiration excluded infection, but
      fluid recollection occurred subsequently. Complete resolution of symptoms,
      including limb swelling, followed surgical excision with no recurrence at the 5
      year follow-up. We believe iliopsoas bursitis occurred as a tissue response to
      polyethylene wear within the prosthetic hip and occurred even in the absence of
      loosening or a direct communication between bursa and joint.

PMID- 15517321
TI  - Complications following the treatment of trochanteric fractures with the gamma
      nail.
AB  - INTRODUCTION: The treatment of trochanteric fractures with the use of gamma nails
      has become an established method. Despite the good and reliable results, some
      typical failures and complications may occur. It was our purpose to analyse the
      most common complications and their treatment options. MATERIALS AND METHODS: A
      total of 498 patients were treated with a gamma nail from January 1992 until
      December 2001. There were 77% pertrochanteric, 10% subtrochanteric, 11% reversed
      pertrochanteric and 2% lateral femoral neck fractures. The patients' mean age was
      78.6 years (ranging from 29 to 98 years). RESULTS: There were a total of 78
      general complications (16%) and implant-related complications in 8% (n=42). The
      most common complication was trochanteric pain necessitating removal of the gamma
      nail (n=30). Four patients fell after removal of the nail and sustained a neck
      fracture on the same side. Cut-out of the screw occurred in 19 patients. Sixteen
      of them had to be converted to a total hip replacement. Another 5 patients were
      converted to a total hip replacement because of pseudoarthrosis. During
      conversion to total hip replacements, the trochanter major refixation and length
      adjustment were the most problematic steps (intra- or postoperative dislocations
      necessitating anti-dislocation rings in three cases). Furthermore, cement
      extrusion at the femur and acetabulum occurred in 13 cases. Infections occurred
      in 3 patients. Five patients with a short gamma nail needed a conversion to a
      long gamma nail due to pseudoarthrosis (n=2) or femur fracture at the distal
      interlocking bolt (n=3). In addition, 7 patients sustained a distal femur
      fracture through the distal bolt, necessitating a plate osteosynthesis.
      CONCLUSION: Most complications after gamma nail fixation can be prevented by
      following certain rules. The other inevitable problems can be dealt with either
      through a conversion to a total hip replacement, a re-osteosynthesis with a long
      gamma nail or an additional condylar plate. Conversion to total hip replacement
      may be a demanding operation with a higher than normal complication rate. Removal
      of the gamma nail should be performed cautiously as re-fractures can occur.

PMID- 15517323
TI  - High sensitivity and reproducibility of immunohistochemistry with microagitation.
AB  - We examined the practicability, reproducibility and analytical sensitivity of
      classical immunohistochemistry (IHC) and IHC with microagitation. Two monoclonal
      antibodies, Ki-67 (proliferation marker) and p53 (tumor suppressor marker), were
      used. Consecutive paraffin sections of biopsies of suspicious lesions of patients
      with non-melanoma skin cancer were used in the study. Reproducibility was
      examined using specimens from four patients in three independent experiments with
      antibodies against Ki-67 and p53. Analytical sensitivity of the two methods was
      determined using serial dilutions in two independent experiments. IHC with
      microagitation could be carried out without destroying the tissue. The new
      technique was consistent and reproducible, and no background staining was
      observed. The primary antibodies Ki-67 and p53 could be used at higher dilutions
      (four to ten times) with microagitation compared with classical IHC.
      Microagitation can be used for immunohistochemistry; it was reproducible, highly
      sensitive, and antibodies could be used at higher dilutions. Further analyses
      with other antibodies using this technique are warranted.

PMID- 15517324
TI  - Patients with a large prostate show a higher prevalence of androgenetic alopecia.
AB  - Androgenetic alopecia (AGA) and benign prostatic hyperplasia (BPH) are both
      androgen-dependent disorders, displaying in situ high levels of
      dihydrotestosterone with a good therapeutic response to finasteride.
      Embryological development of both the hair follicle and the prostate depends on
      mesenchymal-epithelial interaction, which is influenced by the expression of type
      2 5alpha-reductase. The aim of this study was to elucidate the association
      between the size of the prostate gland and the prevalence and severity of AGA. A
      total of 46 patients age between 56 and 87 years were retrospectively recruited.
      They fulfilling the clinical diagnosis of BPH defined as (1) prostate volume > 30
      cm3, measured by transrectal ultrasound, (2) maximal urine flow rate < 15 ml/s
      and mean urine flow rate < 10 ml/s, and (3) prostate serum albumin < 10 ng/ml.
      The control group comprised 34 patients aged between 49 and 81 years with
      urogenital infection, cystitis or urolithiasis. The expression and severity of
      AGA were evaluated by dermatologists using modified Norwood/Hamilton
      classification. Patients with a prostate volume > 30 cm3 had a higher prevalence
      of AGA than patients with a smaller prostate (< 30 cm3) (83.3% vs 61.3%; P <
      0.05). The prostate size, however, did not correlate with the severity of AGA in
      either group or in the whole patient group. The prevalence of AGA was not
      significantly different in patients with or without BPH (85.7% vs 70.6%). The
      prostate was slightly larger among patients with AGA than among those without AGA
      (mean+/-SD 42.7+/-17.4 vs 35.4+/-14.9 cm3), but this was not statistically
      significant. There was no significant correlation between the age of onset of AGA
      and the development of BPH. Our results suggest that a larger prostate is
      associated with a higher prevalence of AGA. It remains to be seen if long-term
      use of finasteride in AGA patients will prophylactically lower the incidence of
      BPH.

PMID- 15517325
TI  - Oviduct contractile response to vaginal distension: identification of vagino
      tubal reflex.
AB  - OBJECTIVE: The effect of vaginal distension on the oviduct contractile activity
      during penile thrusting at coitus could not be traced in the literature. We
      investigated the hypothesis that vaginal distension effects oviduct contraction,
      which assists in ovum transport along the oviduct. METHODS: Oviduct pressure was
      measured upon vaginal condom distension in 16 women (mean age 32.2+/-1.2 years)
      scheduled for abdominal hernia repair and oviduct ligation for sterilization. The
      test was repeated after individual anesthetization of the vagina and oviduct.
      RESULTS: Ten milliliters vaginal distension effected pressure elevation of the
      ampullary (AO) and isthmic (IO) parts of the oviduct (p<0.01, p<0.01
      respectively) and a decrease in intramural oviduct (IMO; p<0.01). Twenty
      milliliters distension further increased the pressure in the AO and the IO
      (p<0.001, p<0.001) and decreased it in IMO (p<0.001). Vaginal distension with
      greater volumes produced an oviduct pressure response similar to that with 20 ml
      distension (p>0.05). Vaginal distension of anesthetized vagina or oviduct did not
      evoke the oviduct pressure response, but saline infusion did. CONCLUSIONS:
      Vaginal distension seems to produce oviduct motile activity as evidenced by
      oviduct pressure changes, which appear to assist in sperm-ovum transport and
      fertilization. These oviduct changes are suggested to occur reflexly through the
      "vagino-tubal reflex." Pathologic changes of the oviduct presumably interfere
      with this reflex action, a point that needs to be investigated.

PMID- 15517326
TI  - Does tibolone affect serum leptin levels and body weight in postmenopausal women?
AB  - OBJECTIVES: Leptin has a significant role in body weight regulation and energy
      balance. We examined the effect of tibolone on the body weight and serum leptin
      levels in postmenopausal women. STUDY DESIGN: Twenty women (aged 43-60 years)
      participated in this prospective study. All women in this study protocol received
      2.5 mg/day of tibolone. Absolute and body mass index (BMI)-corrected serum leptin
      concentrations and BMI values were measured at baseline, after 3 months, and
      after 6 months of the tibolone therapy. RESULTS: Tibolone did not affect absolute
      and BMI-corrected serum leptin levels, and BMI values during the treatment. A
      significant linear correlation between BMI values and serum leptin levels was
      observed (p<0.05, r=0.67). CONCLUSIONS: Tibolone seems not to affect serum leptin
      levels, body weight and BMI values of postmenopausal women. There is a
      significant correlation between serum leptin levels and BMI values.

PMID- 15517327
TI  - A case-control study of congenital abnormality and dimenhydrinate usage during
      pregnancy.
AB  - OBJECTIVE: The objective was to determine the teratogenicity of dimenhydrinate,
      an anti-emetic drug. METHODS: We compared patients with congenital abnormalities
      with matched normal controls. Cases were taken from the population-based data set
      of the Hungarian Case-Control Surveillance of Congenital Abnormalities between
      1980 and 1996, while matched controls were from the National Birth Registry of
      the Central Statistical Office. RESULTS: Out of 38,151 newborn infants with no
      congenital abnormalities (control group), 1,726 (4.5%) were treated with
      dimenhydrinate during pregnancy, while out of 22,843 cases with congenital
      abnormalities, the number was 914 (4.0%; unadjusted prevalence odds ratio with
      95% confidence interval: 0.9, 0.8-1.0). There was thus no indication of
      teratogenicity with dimenhydrinate. However, a lower rate of obstructive uropathy
      was found in infants born to mothers treated with dimenhydrinate during the first
      trimester of pregnancy than in infants whose mothers did not take the drug at
      that time.

PMID- 15517334
TI  - Immunolocalization of protein 4.1B/DAL-1 during neoplastic transformation of
      mouse and human intestinal epithelium.
AB  - Recently, we have reported that the protein 4.1B immunolocalization occurred only
      in matured columnar epithelial cells of normal rat intestines. This finding
      suggested that protein 4.1B expression could be examined for a possible change
      during neoplastic transformation of the intestinal mucosa. In the present study,
      we first present the distribution of mouse protein 4.1B in normal intestinal
      epithelial cells and tumor cells using the adenomatous polyposis coli (Apc)
      mutant mouse model. A low level of protein 4.1B expression coincided with the
      phenotypic transition to carcinoma. To examine the protein 4.1B expression in
      human intestinal mucosa, we used another antibody against an isoform of the human
      protein 4.1B, DAL-1 (differentially expressed adenocarcinoma of the lung). Human
      DAL-1 was also expressed in matured epithelial cells in human colons, with a
      definite expression gradient along the crypt axis. In human colorectal cancer
      cells, however, DAL-1 expression was not detected. These results suggest that
      mouse protein 4.1B and human DAL-1 might have a striking analogy of functions,
      which may be integrally involved in epithelial proliferation. We propose that
      loss of protein 4.1B/DAL-1 expression might be a marker of intestinal tumors,
      indicative of a tumor suppressor function in the intestinal mucosa.

PMID- 15517337
TI  - Norepinephrine as mediator in the stimulation of phagocytosis induced by moderate
      exercise.
AB  - During intensive exercise the stimulation of phagocytosis is mediated by "stress
      hormones". During moderate exercise, however, such mediation is less clear. The
      influence of moderate exercise (45 min at 55% maximal oxygen uptake) on the
      phagocytic capacity of neutrophils was evaluated in sedentary men. The exercise
      stimulated phagocytosis of Candida albicans, and the stimulation was maintained
      for at least 24 h. The possible neuroendocrine mediators were then investigated.
      Stimulation of phagocytosis was found after incubating neutrophils from sedentary
      individuals, who were in a basal state, with plasma from exercised individuals.
      Immediately after exercise, there was a significant increase in the concentration
      of norepinephrine, but not of epinephrine or cortisol. Incubation of neutrophils
      with this post-exercise physiological concentration of norepinephrine also
      stimulated phagocytosis, and the effect was blocked by both propranolol and
      phentolamine. The norepinephrine-augmented phagocytosis was accompanied by an
      increase in intracellular levels of cAMP, but not of cGMP or calcium. In
      conclusion, moderate exercise performed by sedentary people stimulates the
      phagocytic capacity of neutrophils, and the stimulation lasts for at least 24 h.
      Norepinephrine mediates the stimulation, although other mechanisms could be
      involved during the recovery period.

PMID- 15517338
TI  - Strength training does not affect vagal-cardiac control or cardiovagal baroreflex
      sensitivity in young healthy subjects.
AB  - The purpose of this study was to test the hypothesis that high-intensity strength
      training increases vagal-cardiac control and cardiovagal baroreflex sensitivity.
      Twenty-two subjects [age 22 (0.8) years] were assigned to either strength
      training (ST, n=12) or control (CON, n=10) groups. Subjects in the ST group
      trained each major muscle group 3 days per week for 8 weeks with three sets of 10
      repetitions and 2-min rest periods. Resistance was increased progressively when
      possible. Subjects in the CON group were active recreationally but did not lift
      weights. Before and after training, resting arterial pressure was measured with
      an automated sphygmomanometer, and ECG, respiratory rate, and finger
      photoplethysmographic arterial pressures were recorded with subjects supine and
      breathing at a set rate (0.25 Hz) for 5 min. Data were analyzed in both time and
      frequency domains. Arterial baroreflex sensitivity was estimated with the
      sequence method and cross-spectral transfer function analysis of systolic
      pressures and R-R intervals. Training increased whole-body muscular strength and
      decreased arterial blood pressure at rest (the exercise and pressure data have
      been published elsewhere). R-R intervals and standard deviations, and R-R
      interval spectral power at the respiratory frequency were unaffected by training.
      Similarly, training did not affect respiratory or low-frequency systolic pressure
      spectral power or cardiovagal baroreflex sensitivity. Although evidence supports
      beneficial cardiovascular adaptations to resistance training, our results
      demonstrate that resistance training does not affect vagal-cardiac control or
      cardiovagal baroreflex sensitivity in young healthy subjects.

PMID- 15517341
TI  - Neural control exploits changing mechanical advantage and context dependence to
      generate different feeding responses in Aplysia.
AB  - How does neural control reflect changes in mechanical advantage and muscle
      function? In the Aplysia feeding system a protractor muscle's mechanical
      advantage decreases as it moves the structure that grasps food (the
      radula/odontophore) in an anterior direction. In contrast, as the
      radula/odontophore is moved forward, the jaw musculature's mechanical advantage
      shifts so that it may act to assist forward movement of the radula/odontophore
      instead of pushing it posteriorly. To test whether the jaw musculature's context
      dependent function can compensate for the falling mechanical advantage of the
      protractor muscle, we created a kinetic model of Aplysia's feeding apparatus.
      During biting, the model predicts that the reduction of the force in the
      protractor muscle I2 will prevent it from overcoming passive forces that resist
      the large anterior radula/odontophore displacements observed during biting. To
      produce protractions of the magnitude observed during biting behaviors, the
      nervous system could increase I2's contractile strength by neuromodulating I2, or
      it could recruit the I1/I3 jaw muscle complex. Driving the kinetic model with in
      vivo EMG and ENG predicts that, during biting, early activation of the context
      dependent jaw muscle I1/I3 may assist in moving the radula/odontophore anteriorly
      during the final phase of protraction. In contrast, during swallowing, later
      activation of I1/I3 causes it to act purely as a retractor. Shifting the timing
      of onset of I1/I3 activation allows the nervous system to use a mechanical
      equilibrium point that allows I1/I3 to act as a protractor rather than an
      equilibrium point that allows I1/I3 to act as a retractor. This use of
      equilibrium points may be similar to that proposed for vertebrate control of
      movement.

PMID- 15517339
TI  - Effects of 17-day spaceflight on knee extensor muscle function and size.
AB  - It is generally held that space travelers experience muscle dysfunction and
      atrophy during exposure to microgravity. However, observations are scarce and
      reports somewhat inconsistent with regard to the time course, specificity and
      magnitude of such changes. Hence, we examined four male astronauts (group mean
      approximately 43 years, 86 kg and 183 cm) before and after a 17-day spaceflight
      (Space Transport System-78). Knee extensor muscle function was measured during
      maximal bilateral voluntary isometric and iso-inertial concentric, and eccentric
      actions. Cross-sectional area (CSA) of the knee extensor and flexor, and gluteal
      muscle groups was assessed by means of magnetic resonance imaging. The decrease
      in strength (P<0.05) across different muscle actions after spaceflight amounted
      to 10%. Eight ambulatory men, examined on two occasions 20 days apart, showed
      unchanged (P>0.05) muscle strength. CSA of the knee extensor and gluteal muscles,
      each decreased (P<0.05) by 8%. Knee flexor muscle CSA showed no significant
      (P>0.05) change. The magnitude of these changes concord with earlier results from
      ground-based studies of similar duration. The results of this study, however, do
      contrast with the findings of no decrease in maximal voluntary ankle plantar
      flexor force previously reported in the same crew.

PMID- 15517340
TI  - High-energy phosphate metabolism during two bouts of progressive calf exercise in
      humans measured by phosphorus-31 magnetic resonance spectroscopy.
AB  - According to the literature the steady-state level of phosphocreatine (PCr) has a
      linear relationship to the workload during muscle exercise intensities below the
      lactate threshold, whereas this linearity is impaired during exercise intensities
      above the lactate threshold. The purpose of this study was to investigate the
      linearity between PCr kinetics and workload during two bouts of isotonic
      incremental calf exercise with transitions from moderate- to high-intensity as
      well as from high- to moderate-intensity work rates. Using a whole-body 1.5 T MR
      scanner and a self-built exercise bench, we performed serial phosphorus-31
      magnetic resonance spectroscopy ((31)P-MRS) with a time resolution of 30 s in
      nine healthy male volunteers. Changes in PCr, inorganic phosphate (Pi) and pH
      were statistically evaluated in comparison to the baseline. The exercise protocol
      started with a 4.5 W interval of 6 min followed by two bouts of 1.5 W increments.
      The workload was increased in 2-min intervals up to 9 W during the first bout and
      up to 7.5 W during the second bout. The second bout was preceded by a 4.5 W
      interval of 2 min and followed by a 4.5 W interval of 4 min. PCr hydrolysis
      achieved a steady state during each increment and was highly linear to the work
      rate (r (2), -0.796; P <0.001). Pi accumulated during each bout, whereas the pH
      decreased continuously during the first bout and did not exhibit any substantial
      decrease during the second bout. The metabolite levels and pH were expressed as
      the median value and the range. Our study confirms that steady-state PCr levels
      also have a linear relationship to work intensities above the lactate threshold,
      while pH changes do not have any impact on PCr degradation. The lack of
      substantial changes in pH during the second exercise bout indicates that prior
      high-intensity exercise leads to an activation of oxidative phosphorylation.

PMID- 15517342
TI  - Increase in intracellular Cl- concentration by cAMP- and Ca2+-dependent
      stimulation of M1 collecting duct cells.
AB  - In the lungs of cystic fibrosis (CF) patients, mutations of the cystic fibrosis
      transmembrane conductance regulator (CFTR) lead to defective Cl- secretion and
      hyperabsorption of electrolytes. This may be a an important cause for the
      defective mucociliary clearance in CF lungs. Previous studies have suggested that
      inhibition of ENaC during activation of CFTR or by purinergic stimulation could
      be related to an increase in the intracellular [Cl-]i. This was examined in the
      present study using cultured mouse M1 collecting duct cells transfected with the
      chloride-sensitive enhanced yellow fluorescent protein YFP(V163S). Calibration
      experiments showed a linear decrease of YFP fluorescence intensity with
      increasing [Cl-]i (0-100 mM). Activation of CFTR by isobutyl-1-methylxanthine
      (IBMX, 100 microM) and forskolin (2 microM) increased [Cl-]i by 9.6+/-1.5 mM
      (n=35). Similarly, ATP (100 microM) increased [Cl-]i transiently by 9.5+/-2.2 mM
      (n=17). The increase in [Cl-]i was reduced by the Na+/K+/2 Cl- -cortransporter-1
      (NKCC1) blocker azosemide (100 microM), the CFTR blocker SP-303 (50 microM), the
      blocker of Ca2+-activated Cl- channels DIDS (100 microM) or the ENaC blocker
      amiloride (10 microM). Changes in YFP(V163S) fluorescence were not due to changes
      in cell volume or intracellular pH. The present data thus demonstrate an increase
      in [Cl-]i following stimulation with secretagogues, which could participate in
      the inhibition of ENaC.

PMID- 15517343
TI  - Expression and regulation of the renal Na/phosphate cotransporter NaPi-IIa in a
      mouse model deficient for the PDZ protein PDZK1.
AB  - Inorganic phosphate (P(i)) is reabsorbed in the renal proximal tubule mainly via
      the type-IIa sodium-phosphate cotransporter (NaPi-IIa). This protein is regulated
      tightly by different factors, among them dietary P(i) intake and parathyroid
      hormone (PTH). A number of PDZ-domain-containing proteins have been shown to
      interact with NaPi-IIa in vitro, such as Na(+)/H(+) exchanger-3 regulatory factor
      1 (NHERF1) and PDZK1. PDZK1 is highly abundant in kidney and co-localizes with
      NaPi-IIa in the brush border membrane of proximal tubules. Recently, a knock-out
      mouse model for PDZK1 (Pdzk1(-/-)) has been generated, allowing the role of PDZK1
      in the expression and regulation of the NaPi-IIa cotransporter to be examined in
      in vivo and in ex vivo preparations. The localization of NaPi-IIa and other
      proteins interacting with PDZK1 in vitro [Na(+)/H(+) exchanger (NHE3), chloride
      formate exchanger (CFEX)/putative anion transporter-1 (PAT1), NHERF1] was not
      altered in Pdzk1(-/-) mice. The abundance of NaPi-IIa adapted to acute and
      chronic changes in dietary P(i) intake, but steady-state levels of NaPi-IIa were
      reduced in Pdzk1(-/-) under a P(i) rich diet. This was paralleled by a higher
      urinary fractional P(i) excretion. The abundance of the anion exchanger CFEX/PAT1
      (SLC26A6) was also reduced. In contrast, NHERF1 abundance increased in the brush
      border membrane of Pdzk1(-/-) mice fed a high-P(i) diet. Acute regulation of NaPi
      IIa by PTH in vivo and by PTH and activators of protein kinases A, C and G (PKA,
      PKC and PKG) in vitro (kidney slice preparation) was not altered in Pdzk1(-/-)
      mice. In conclusion, loss of PDZK1 did not result in major changes in proximal
      tubule function or NaPi-IIa regulation. However, under a P(i)-rich diet, loss of
      PDZK1 reduced NaPi-IIa abundance indicating that PDZK1 may play a role in the
      trafficking or stability of NaPi-IIa under these conditions.

PMID- 15517347
TI  - Role of protein kinase C in the excitatory action of cholinergic nerve
      stimulation on spontaneous activity of circular smooth muscle isolated from the
      guinea-pig stomach antrum.
AB  - Following inhibition of NO production with nitroarginine, circular muscle
      isolated from the guinea-pig gastric antrum generated periodic slow potentials
      and unitary potentials. Transmural nerve stimulation (TNS) during the interval
      between slow potentials evoked an apamin-sensitive inhibitory junction potential
      (IJP) followed by an atropine-sensitive depolarization; the latter was either a
      transient depolarization with enhanced generation of unitary potentials or a slow
      potential. After inhibition of unitary potentials and slow potentials with 1 mM
      caffeine, TNS evoked an IJP and subsequent cholinergic depolarization, the latter
      developing slowly and lasting for about 10 s. TNS was unable to elicit a slow
      potential until a certain period of time had elapsed following the cessation of a
      slow potential. The period during which TNS could not evoke slow potentials
      (termed the high-threshold period) was about 10 s, and this period was increased
      by chelerythrine and decreased by phorbol esters. It is concluded that
      cholinergic nerve-mediated excitation of gastric muscle involves the activation
      of protein kinase C (PKC), and that the high-threshold period, during which the
      generation of slow potentials by TNS is inhibited, may be a consequence of
      reduced activity of PKC.

PMID- 15517344
TI  - Disentangling the molecular mechanisms of action of endogenous and environmental
      estrogens.
AB  - The gonadal hormone 17beta-estradiol is involved in numerous cellular processes.
      In many cases, 17beta-estradiol actions are imitated by synthetic and natural
      chemicals in the environment. Their actions differ depending on the target
      tissue, the receptors involved and the molecular pathways activated. The plethora
      of estrogenic actions is triggered by different receptors and other specific
      structures that activate different signalling pathways. This amount of
      information may lead to a maze of effects triggered by endogenous and
      environmental estrogens that we intend to clarify in this review. Understanding
      the variety of estrogen receptors, their different locations and the signalling
      pathways activated by estrogenic ligands is fundamental for understanding the
      diversity of actions that estrogens have in different tissues and cells.

PMID- 15517348
TI  - Expression of beta-galactosidase and beta-xylosidase genes during microspore and
      pollen development.
AB  - Tobacco (Nicotiana tabacum L.) microspores at the time of mitosis are
      characterized by the abundant occurrence of 92- and 98-kDa glycoproteins (GP92
      and GP98). GP92 is a soluble protein while GP98 is bound to the insoluble
      microspore fraction. Both glycoproteins were isolated by affinity chromatography
      and SDS-PAGE and analysed by MS. Peptide sequences were determined by mu
      HPLC/nano-ESI-MS/MS (electrospray ionization tandem MS). GP92 displayed homology
      to beta-galactosidase (EC 3.2.1.23) and GP98 to beta-xylosidase (EC 3.2.1.37)
      from Arabidopsis thaliana (L.) Heynh. The activities of the two enzymes in
      microspore and pollen extracts of tobacco exhibited similar developmental changes
      to the occurrence of GP92 and GP98, with a maximum around microspore mitosis.
      These two glycoproteins are the first identified enzymes characteristic of
      mitotic microspores. Arabidopsis transcriptomic data for five beta-galactosidase
      and three beta-xylosidase genes abundantly expressed in pollen were verified by
      reverse transcription-PCR of RNA from different stages of Arabidopsis pollen
      development and from various parts of the sporophyte. The results showed abundant
      expression of two genes (At5g20710, At1g31740) homologous to tobacco GP92 in
      microspores and early pollen, and of three genes (At5g56870, At2g16730 and
      At4g35010) in maturing pollen. Analysis of beta-xylosidases showed abundant
      expression of a late pollen-specific gene At3g62710 and low expression of an
      early gene At5g10560. It is suggested that the early beta-galactosidase and beta
      xylosidase genes may participate in cell wall loosening associated with pollen
      expansion after microspore mitosis and that the products of the late genes may
      play a role in cell expansion during pollen germination.

PMID- 15517349
TI  - A cut above the rest: the regulatory function of plant proteases.
AB  - Proteolytic enzymes are intricately involved in many aspects of plant physiology
      and development. On the one hand, they are necessary for protein turnover.
      Degradation of damaged, misfolded and potentially harmful proteins provides free
      amino acids required for the synthesis of new proteins. Furthermore, the
      selective breakdown of regulatory proteins by the ubiquitin/proteasome pathway
      controls key aspects of plant growth, development, and defense. Proteases are, on
      the other hand, also responsible for the post-translational modification of
      proteins by limited proteolysis at highly specific sites. Limited proteolysis
      results in the maturation of enzymes, is necessary for protein assembly and
      subcellular targeting, and controls the activity of enzymes, regulatory proteins
      and peptides. Proteases are thus involved in all aspects of the plant life cycle
      ranging from the mobilization of storage proteins during seed germination to the
      initiation of cell death and senescence programs. This article reviews recent
      findings for the major catalytic classes, i.e. the serine, cysteine, aspartic,
      and metalloproteases, emphasizing the regulatory function of representative
      enzymes.

PMID- 15517350
TI  - Investigation on Semecarpus Lehyam--a Siddha medicine for breast cancer.
AB  - The use of complementary and alternative medicines for breast cancer patients has
      been increasing every year. Traditional Indian systems of medicine, such as
      Siddha, have been reported to benefit patients in India through herbal
      interventions for cancer. One such herbal medicine is Semecarpus Lehyam (SL), and
      this study aims at providing a scientific basis for the anti-tumor property of SL
      with respect to breast cancer. SL was subjected to serial extraction with four
      organic solvents of increasing polarity (n-hexane, chloroform, ethyl acetate, n
      butanol and water). The solvents from all fractions were removed, dried and
      dissolved in dimethyl sulfoxide for testing their anti-tumor activity against two
      breast cancer cell lines, MCF-7 [estrogen receptor (ER)-positive] and MDA 231 (ER
      negative) using cell viability and apoptosis assays. The most potent SL fractions
      were also combined with radiation and doxorubicin to determine the radio- and
      chemo-sensitizing effects of SL on these breast cancer cell lines. In terms of
      cytotoxicity as well as induction of apoptosis, the n-hexane and chloroform
      fractions of SL were more significantly active against MDA 231 cells than MCF-7
      cells. The n-butanol fraction of SL showed some activity against MCF-7 cells.
      When combined with radiation or doxorubicin, the n-hexane and chloroform
      fractions enhanced the radio-sensitivity (11.8-fold) and chemo-sensitivity (6.5
      fold) of MDA 231 cells. This study demonstrated SL to be a potent anti-tumor
      agent against the ER-negative breast cancer cell line. The study is also the
      first step in the scientific validation of SL for use against breast cancer,
      particularly the ER-negative type.

PMID- 15517351
TI  - Polyamines inhibit NADPH oxidase-mediated superoxide generation and putrescine
      prevents programmed cell death induced by polyamine oxidase-generated hydrogen
      peroxide.
AB  - Our previous results indicate that during protoplast isolation an oxidative burst
      occurs [A.K. Papadakis and KA Roubelakis-Angelakis (1999) Plant Physiol 127:197
      205] and that suppression of totipotency is correlated with reduced antioxidant
      activity and low redox state [A.K. Papadakis et al. (2001b) Plant Physiol 126:434
      444]. Polyamines are known to affect cell development and to act as antioxidants.
      Polyamines applied during isolation of tobacco (Nicotiana tabacum L.) protoplasts
      reduced the accumulation of O2*- but not that of H2O2. This antioxidant effect is
      probably due to the inhibition of microsomal membrane NADPH oxidase, which
      occurred in a concentration-dependent manner, with spermine exerting the highest
      inhibitory effect. However, during protoplast culture, polyamine oxidase activity
      increased severalfold in spermidine- and spermine-treated protoplasts,
      concomitant with H2O2 titers. A cell death program was executed in untreated
      protoplasts, as documented by membrane malfunction, induced DNase activity, DNA
      fragmentation and a positive TUNEL reaction. Protoplast cell death was prevented
      in protoplasts treated with putrescine, but not by treatment with spermidine or
      spermine, which rather had the opposite effect. The data presented suggest that
      PAs may be implicated in the expression of plant protoplast totipotency.

PMID- 15517352
TI  - Sucrose partitioning between vascular bundles and storage parenchyma in the
      sugarcane stem: a potential role for the ShSUT1 sucrose transporter.
AB  - A transporter with homology to the SUT/SUC family of plant sucrose transporters
      was isolated from a sugarcane (Saccharum hybrid) stem cDNA library. The gene,
      designated ShSUT1, encodes a protein of 517 amino acids, including 12 predicted
      membrane-spanning domains and a large central cytoplasmic loop. ShSUT1 was
      demonstrated to be a functional sucrose transporter by expression in yeast. The
      estimated K(m) for sucrose of the ShSUT1 transporter was 2 mM at pH 5.5. ShSUT1
      was expressed predominantly in mature leaves of sugarcane that were exporting
      sucrose and in stem internodes that were actively accumulating sucrose.
      Immunolocalization with a ShSUT1-specific antiserum identified the protein in
      cells at the periphery of the vascular bundles in the stem. These cells became
      lignified and suberized as stem development proceeded, forming a barrier to
      apoplasmic solute movement. However, the movement of the tracer dye,
      carboxyfluorescein from phloem to storage parenchyma cells suggested that
      symplasmic connections are present. ShSUT1 may have a role in partitioning of
      sucrose between the vascular tissue and sites of storage in the parenchyma cells
      of sugarcane stem internodes.

PMID- 15517353
TI  - Two genes encoding different truncated hemoglobins are regulated during root
      nodule and arbuscular mycorrhiza symbioses of Medicago truncatula.
AB  - The MtTrHb1 and MtTrHb2 genes of the model legume Medicago truncatula Gaertn.
      encode proteins homologous to truncated hemoglobins (TrHb) from plants and a
      range of different microorganisms. Induction of MtTrHb1 in root nodules and
      expression of MtTrHb2 in root nodules, as well as in mycorrhizal roots, were
      shown by quantitative real-time reverse transcription-polymerase chain reaction
      (RT-PCR). The promoters of both genes were PCR-amplified and fused to the gusAint
      coding region. By analysing these gusAint-fusions in transgenic root tissues, we
      were able to localize their activity in root nodules and in roots colonized by
      arbuscular mycorrhizal (AM) fungi. Whereas the promoter of MtTrHb1 was activated
      in the infected cells of the nitrogen-fixing zone of root nodules, the MtTrHb2
      promoter was predominantly active in the nodule vascular tissue. This expression
      pattern correlates with the presence of an 'organ-specific element' (OSE)-like
      sequence in the MtTrHb1 promoter, which is not present in the MtTrHb2 regulatory
      unit. Concerning the AM symbiosis, only the MtTrHb2 promoter mediated an
      expression in arbuscule-containing cells and in the root vascular tissue of
      mycorrhizal root segments colonized by the fungus Glomus intraradices.

PMID- 15517354
TI  - Subcellular localisation of Cd and Zn in the leaves of a Cd-hyperaccumulating
      ecotype of Thlaspi caerulescens.
AB  - Thlaspi caerulescens (Ganges ecotype) is able to accumulate large concentrations
      of cadmium (Cd) and zinc (Zn) in the leaves without showing any toxicity,
      suggesting a strong internal detoxification. The distribution of Cd and Zn in the
      leaves was investigated in the present study. Although the Cd and Zn
      concentrations in the epidermal tissues were 2-fold higher than those of
      mesophyll tissues, 65-70% of total leaf Cd and Zn were distributed in the
      mesophyll tissues, suggesting that mesophyll is a major storage site of the two
      metals in the leaves. To examine the subcellular localisation of Cd and Zn in
      mesophyll tissues, protoplasts and vacuoles were isolated from plants exposed to
      50 muM Cd and Zn hydroponically. Pure protoplasts and vacuoles were obtained
      based on light-microscopic observation and the activities of marker enzymes of
      cytosol and vacuoles. Of the total Cd and Zn in the mesophyll tissues, 91% and
      77%, respectively, were present in the protoplast, and all Cd and 91% Zn in the
      protoplast were localised in the vacuoles. Furthermore, about 70% and 86% of
      total Cd and Zn, respectively, in the leaves were extracted in the cell sap,
      suggesting that most Cd and Zn in the leaves is present in soluble form. These
      results indicate that internal detoxification of Cd and Zn in Thlaspi
      caerulescens leaves is achieved by vacuolar compartmentalisation.

PMID- 15517355
TI  - A rapid response of beta-amylase to nitric oxide but not gibberellin in wheat
      seeds during the early stage of germination.
AB  - The effects of nitric oxide (NO) and gibberellic acid (GA(3)) on the responses of
      amylases in wheat (Triticum aestivum L.) seeds (caryopses) were investigated
      during the first 12 h of germination. GA(3) had no effects on the activities of
      alpha-amylase (EC 3.2.1.1) or beta-amylase (EC 3.2.1.2), either in intact seeds
      or embryoless halves within 12 h. In contrast, addition of sodium nitroprusside
      (SNP), an NO donor, was able to induce a rapid increase in beta-amylase activity
      without affecting alpha-amylase. Furthermore, the rapid response of beta-amylase
      to SNP in wheat seeds could be attributed to NO and was approximately dose
      dependent. Some other aspects of SNP induction of amylase isozymes were also
      characterized. Further investigations showed that SNP might play an interesting
      role in the dissociation of free beta-amylase from small homopolymers or
      heteropolymers. Furthermore, SNP also directly induced the release of bound beta
      amylase from glutenin and its crude enzyme preparation. However, the slight
      increase in protease also induced by SNP might not be responsible for this
      action. Interestingly, based on the fact that the rapid response of beta-amylase
      to NO also existed in seeds of other species, such as barley, soybean, rice and
      watermelon, it might be a universal event in early seed germination.

PMID- 15517356
TI  - Expression of Escherichia coli branching enzyme in caryopses of transgenic rice
      results in amylopectin with an increased degree of branching.
AB  - Physiochemical properties of starch are dependent on several factors including
      the relative abundance of amylose and amylopectin, and the degree of branching of
      amylopectin. Utilizing Agrobacterium-mediated transformation, a construct
      containing the coding region of branching enzyme of Escherichia coli, under
      transcriptional control of the rice (Oryza sativa L.) starch-branching enzyme
      promoter was introduced into rice cv. Nakdong. To enhance glgB expression, the
      first intron of rice starch-branching enzyme and the matrix attachment region
      (MAR) sequence from chicken lysozyme were included in the expression vector.
      Eleven independent transgenic rice plants were generated. Southern blot analysis
      indicated that the copy number of glgB integrated into transgenic rice varied
      from one to five. High-performance liquid chromatographic analysis of starch from
      transgenic lines revealed that amylopectin from transgenic lines exhibited
      greater branching than that of non-transgenic rice. The A/B1 ratio in amylopectin
      increased from 1.3 to 2.3 and the total branching ratio, A+B1/B-rest, increased
      from 6 to 12 in transgenic rice. The observed increase in the short-chain
      fractions with a degree of polymerization between 6 and 10 is expected to have a
      significant effect on retrogradation. Our study demonstrates that amylopectin
      branching can be altered in vivo, thus changing the physicochemical properties of
      starch.

PMID- 15517357
TI  - Biophysical consequences of remodeling the neutral side chains of
      rhamnogalacturonan I in tubers of transgenic potatoes.
AB  - Two lines of transgenic potato (Solanum tuberosum L.) plants modified in their
      cell wall structure were characterized and compared to wild type with regard to
      biomechanical properties in order to assign functional roles to the particular
      cell wall polysaccharides that were targeted by the genetic changes. The targeted
      polymer was rhamnogalacturonan I (RG-I), a complex pectic polysaccharide
      comprised of mainly neutral oligosaccharide side chains attached to a backbone of
      alternating rhamnosyl and galacturonosyl units. Tuber rhamnogalacturonan I
      molecules from the two transformed lines are reduced in linear galactans and
      branched arabinans, respectively. The transformed tuber tissues were found to be
      more brittle when subjected to uniaxial compression and the side-chain truncation
      was found to be correlated with the physical properties of the tissue.
      Interpretation of the force-deflection curves was aided by a mathematical model
      that describes the contribution of the cellulose microfibrils, and the results
      lead to the proposition that the pectic matrix plays a role in transmitting
      stresses to the load-bearing cellulose microfibrils and that even small changes
      to the rheological properties of the matrix have consequences for the biophysical
      properties of the wall.

PMID- 15517358
TI  - A novel mutant with modified tropic responses in Pisum sativum L.
AB  - A single-gene recessive mutant which displays increased phototropic and
      gravitropic responses has been isolated in Pisum sativum L. cv. Torsdag and is
      provisionally named mtr-1, for its modified tropic response. Mutant plants attain
      a greater degree of bending during both phototropic and gravitropic induction due
      to an extension of the curvature phase. In addition to their increase in tropic
      curvature, mutant plants have longer and narrower leaves as mature plants,
      attenuated blue-light-induced ion flux responses, and lower levels of PsPK5 mRNA
      (a PHOT1 orthologue). Possible causes of these effects are discussed.

PMID- 15517359
TI  - Histopathological features of diagnostic and clinical relevance in autoimmune
      pancreatitis: a study on 53 resection specimens and 9 biopsy specimens.
AB  - BACKGROUND AND AIMS: Autoimmune pancreatitis seems to be a disease with a
      heterogeneous appearance. Our intention was to establish key diagnostic criteria,
      define grades of severity and activity, identify features of potential subtypes
      and evaluate the diagnostic relevance of biopsy specimens. METHODS:
      Histopathological criteria and clinical features were recorded in pancreatic
      resection specimens from 53 patients who were found to have chronic pancreatitis
      lacking pseudocysts, calculi, irregular duct dilatations, pancreas divisum and/or
      duodenal wall inflammation. The severity of the chronic inflammation was graded,
      and the activity of the acute inflammatory component and the granulocytic
      epithelial lesion (GEL) were determined. Additionally, pancreatic biopsy
      specimens from 9 patients with suspected AIP were assessed. RESULTS: Periductal
      lymphoplasmacytic infiltration was identified in all cases, followed in order of
      frequency by periductal fibrosis and venulitis. These changes were absent in 147
      pancreatic specimens that showed chronic pancreatitis associated with
      pseudocysts, calculi, pancreas divisum and/or duodenal wall inflammation. In 90%
      of the cases, these chronic changes were graded as 3 or 4. In 81%, the
      inflammatory process resided in the head of the pancreas and involved the common
      bile duct. GELs were present in 42% of the patients, who had a mean age of 40.5
      years, an almost equal male-female ratio and a high coincidence of ulcerative
      colitis or Crohn's disease. Patients without GELs were older (mean age 64 years),
      showed a male preponderance, commonly had Sjogren's syndrome and often developed
      recurrent bile-duct stenosis. Diagnostically relevant lesions were present in two
      of five wedge biopsy specimens and three of four fine-needle specimens.
      CONCLUSIONS: Periductal lymphoplasmacytic infiltration and fibrosis, preferential
      occurrence in the pancreatic head and venulitis characterize autoimmune
      pancreatitis. GELs predominantly occur in a subset of patients who are younger,
      more commonly have ulcerative colitis and Crohn's disease and seem to have fewer
      recurrences than patients without GELs. Pancreatic biopsy material proved to be a
      very helpful adjunct for establishing the diagnosis.

PMID- 15517360
TI  - Regeneration of gastric mucosa during ulcer healing follows pathways that
      correspond to the ontogenetic course of rat fundic glands.
AB  - Gastric ulcers in humans are notoriously chronic and recurring lesions. Although
      the average individual who undergoes no treatments requires many years for
      healing, most studies on the healing process of the experimentally induced ulcers
      have mainly focused on the early stages. Natural history of the ulcer healing has
      not been completely revealed. We have undertaken long-term investigation up to
      the 150th day after the cryo-injury to shed light on the natural history of the
      ulcer healing process compared with developmental changes of postnatal fundic
      glands. By the 30th day, restitutive gastric glands were mostly seen to cover the
      ulcer lesions, where well-developed gland-type mucous cells, showing Griffonia
      simplicifolia agglutinin (GSA)-II labeling, appeared to occupy the basal portion.
      Most of the bromodeoxyuridine-labeled cells were superimposed on the GSA-II
      positive cell zone, forming the proliferative zone. By the 150th day, the
      restitutive glands were complete, with all epithelial components and topology of
      the normal fundic glands. The process of the ulcer healing was quite compatible
      with the developmental changes of the postnatal fundic glands. These results
      imply that the regeneration of gastric epithelium during the ulcer healing
      follows pathways linked to the ontogenetic course of the fundic gland.

PMID- 15517361
TI  - Aberrant acinar cell CA 19-9 expression and peri-insular acinar cell alterations
      in an adult human pancreas.
AB  - We herein report on a 23-year-old female patient who suffered from Crohn's
      disease and anorexia nervosa and died after long-term malnutrition and a
      perforated colitis. At autopsy, her pancreas displayed two peculiar findings.
      First, there was a constant and aberrant expression of CA 19-9 in the acinar
      cells. The expression of the carbohydrate antigen CA 19-9 is normally confined to
      duct-like epithelia, including centroacinar cells, while islet and acinar cells
      have repeatedly been reported to be immunohistochemically negative. Thus, to the
      best of our knowledge, our case is the first to show aberrant acinar CA 19-9
      expression, and its potential meaning is discussed. Second, the pancreas showed a
      heterogeneity in acinar morphology, with peri-insular acini being considerably
      larger than tele-insular acini. The existence of enlarged peri-insular acini,
      mainly in animals, has occasionally been reported. Its origin, however, is still
      unclear. Some authors have proposed an influence of high insulin concentrations,
      exerted via the insulo-acinar capillary axis. We agree with the concept of an
      islet-derived mechanism. However, as we have observed a similar heterogeneity in
      streptozotocin- and autoimmune-diabetic rats, we presume that other islet
      hormones, in particular glucagon, might be more important for this phenomenon in
      the animals, as well as in the present case.

PMID- 15517362
TI  - Identification of a lower grade muconodular subtype of gastric mucinous cancer.
AB  - Until now, survival analysis of gastric mucinous cancers showed either no
      difference or an even worse prognosis than stage-adjusted non-mucinous tumours.
      In the pancreas and breast, mucinous cancers showing well-demarcated mucin
      deposits (muconodular pattern), expansile growth and predominance of MUC2 mucin
      are known to have a more favourable prognosis. In this study, an attempt was made
      to separate, among 41 gastric mucinous cancers, a subgroup of tumours with
      muconodular expansile pattern, possibly predictive of a more favourable outcome.
      A group of 15 tumours was identified, which were characterised by overwhelming
      (80-100%) mucinous component, predominance of mucus over tumour cells inside
      muconodules, moderately aggressive growth of their epithelial component (reduced
      proliferative rate, moderate anaplasia, lack of angioinvasion and limited
      lymphoinvasion) and dominant expression of intestinal goblet cell markers, with
      special reference to MUC2 mucin. Univariate and multivariate survival analysis
      showed a significantly improved outcome of these lower grade muconodular tumours
      compared with the remaining mucinous cancers as well as with non-mucinous cancers
      of cohesive, diffuse (signet-ring cell included) and undifferentiated high-grade
      types.

PMID- 15517363
TI  - CD10 expression in diffuse large B-cell lymphomas does not influence survival.
AB  - CD10 expression is considered as a marker of centrofollicular-derived diffuse
      large B-cell lymphomas (DLBCL). The aim of our study was to determine
      retrospectively among 98 patients with DLBCL, enrolled in the LNH93 trial of the
      Groupe d'Etude des Lymphomes de l'Adulte (GELA) and homogeneously treated with
      high-dose cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)-like
      regimen [doxorubicin, cyclophosphamide, vindesine, bleomycin and prednisone
      (ACVBP)], the expression of CD10 using immunohistochemistry and its correlation
      with morphological features and clinical parameters. Of the 98 patients studied,
      33 (34%) expressed CD10. There was no correlation among clinical parameters,
      International Prognostic Index risk groups and CD10 expression, with the
      exception of lactic dehydrogenase levels, which were lower in CD10-negative cases
      (P=0.005). There was no significant correlation between CD10 expression and
      morphological subtyping of DLBCL. Indeed, centrofollicular-derived DLBCL may
      present with numerous immunoblasts or as an immunoblastic lymphoma. Overall
      survival rate and event-free survival were not significantly different according
      to CD10 expression (P=0.44 and P=0.34 respectively). Therefore, it appears that
      CD10 expression does not influence survival or event-free survival in DLBCL.

PMID- 15517364
TI  - Atypical/bizarre spindle-cell epithelial metaplasia in nodular goiter: a
      potential diagnostic pitfall.

PMID- 15517365
TI  - Anaplastic carcinoma of the thyroid with rhabdomyosarcomatous differentiation: a
      report of two cases.
AB  - Anaplastic carcinoma of the thyroid gland (ACT) is a highly malignant tumor that
      is almost invariably associated with a fatal outcome. It demonstrates a variety
      of peculiar histological features, with squamoid, giant cell and spindle cell
      growth patterns. The spindle cell variant of ACT is usually indistinguishable
      from a true sarcoma and it can simulate fibrosarcoma, malignant fibrous
      histiocytoma (MFH), hemangiopericytoma and angiosarcoma or rhabdomyosarcoma.
      Although a rhabdomyosarcomatous appearance has sometimes been mentioned in the
      literature, true skeletal muscle differentiation has never been consistently
      proved. We report two cases of ACT with rhabdomyosarcomatous differentiation, as
      demonstrated by means of immunohistochemistry and electron microscopy. Both cases
      disclosed a very similar histological appearance, with a main population of
      small, pleomorphic, round-to-oval cells arranged in a storiform pattern, admixed
      with scattered pleomorphic giant cells, an image similar to that of the usual
      type of MFH. Stains for epithelial markers showed only few, scattered, weakly
      positive cells. Thyroglobulin and calcitonin were negative in tumor cells in both
      cases. On the contrary, positivity to vimentin was strong and generalized.
      Immunomarkers of muscular differentiation showed a consistent positivity. At the
      ultrastructural level, the cells disclosed the same spindle and pleomorphic
      morphology, with large, bizarre nuclei and cytoplasm with abundant mitochondria,
      rough endoplasmic reticulum, secretory granules and lipid droplets. There were
      also cells with wide cytoplasm filled with filamentous material, either of actin
      or myosin, as well as Z-band material. In conclusion, the cases reported here
      show a clear-cut rhabdomyosarcomatous differentiation of ACT, confirmed both
      immunohistochemically and ultrastructurally, a feature not previously reported in
      the literature. These findings may contribute to the broadening of the
      differentiation spectrum of this unusual neoplasm.

PMID- 15517366
TI  - Biological significance of p27 and Skp2 expression in renal cell carcinoma. A
      systematic analysis of primary and metastatic tumour tissues using a tissue
      microarray technique.
AB  - p27 (p27/kip1) is involved in cell-cycle control, and loss of p27 expression may
      result in tumour development and/or progression. Association with Skp2 targets
      p27 for degradation. Using a tissue microarray technique, 171 primary renal cell
      carcinomas (RCCs) and 58 RCC metastases were immunostained for p27 and Skp2. p27
      Immunoreactivity was noted in 83 of 129 (64%) clear cell, 6 of 22 (27%)
      chromophobe and 15 of 20 (75%) papillary tumours as well as 44 of 58 (76%)
      metastases. In clear cell cancers, high p27 expression (> or =50% of tumour
      cells) decreased with rising tumour stage (50% pT1/pT2 versus 20% pT3; P<0.001)
      and grade (44% G1/G2 versus 21% G3/G4; P=0.008). None of 22 chromophobe cancers
      showed high expression in contrast to 46 of 129 (36%) clear cell tumours
      (P<0.001). Skp2 expression was noted in 8 of 129 (6%) clear cell cancers and 11
      of 55 (20%) metastases (P=0.008). Immunoreactivity increased with rising tumour
      stage (1% pT1/pT2 versus 11% pT3; P=0.03) and grade (1% G1/G2 versus 15% G3/G4;
      P=0.004) and was associated with sarcomatoid morphology (P<0.001). In
      multivariate analysis, patients with low p27 expression and Skp2 immunoreactivity
      in clear cell cancers had a less favourable outcome. In conclusion, p27 and Skp2
      proved to be additional biomarkers in renal cancer pathology with both prognostic
      and diagnostic impact.

PMID- 15517367
TI  - Mixed acinar-endocrine carcinoma of the pancreas. A clinicopathological study and
      comparison with acinar-cell carcinoma.
AB  - We compared the clinicopathological features of acinar-cell carcinomas (ACCs)
      with those of mixed acinar-endocrine carcinomas (MAECs). Specimens from 37
      patients with ACC and 6 patients with MAEC were examined histologically and
      immunohistochemically. The mean age of ACC and MAEC patients was similar (61.3
      years versus 58.4 years), but the sex ratio differed (ACC, 29 males and 8
      females; MAEC, 2 males and 4 females). The size of the tumor was large in both
      cases (ACC, 13.8 cm in diameter; MAEC, 8.2 cm). Immunohistochemically, more than
      half of the tumor cells in all tumors, whether ACC or MAEC, stained for trypsin.
      In 20 of the 37 ACCs (54%), scattered endocrine cells (SECs) were found, which
      stained positively for synaptophysin (SYN) and/or chromogranin A (CGA).
      Interestingly, there was also a difference in the sex ratio between ACC patients
      without SECs (16 males and 1 female) and ACC patients with SECs (13 males and 7
      females). In MAECs, the cells staining for SYN were more common than those
      staining for CGA and made up more than one-third of the neoplastic-cell
      population. In all but one case (in which the endocrine component was arranged in
      islet-like cell clusters), the endocrine cells were intimately mixed with trypsin
      positive tumor cells. The endocrine cells only rarely expressed one of the known
      pancreatic or gastrointestinal hormones. Both ACCs and MAECs had a high
      proliferation rate and lacked p53 overexpression or progesterone and estrogen
      receptors. This study revealed that ACCS and MAECs share most clinicopathological
      features and, therefore, may form a single tumor entity, though they differ in
      the number of endocrine cells. The frequent identification of endocrine cells in
      these tumors suggests the existence of a pluripotent cell of origin that is
      capable of differentiating into acinar and endocrine cells.

PMID- 15517368
TI  - CDX2 as a marker of intestinal EC-cells and related well-differentiated endocrine
      tumors.
AB  - Gastroenteropancreatic (GEP) endocrine tumors (ETs) are neoplasms showing
      different hormonal profiles and different clinical and prognostic features, which
      depend consistently on the site of origin. Histological features and general
      endocrine markers do not differentiate tumors in relation to their location,
      making it difficult to establish the site of origin of a GEP ET that has
      metastasized to the liver or lymph nodes. A site-specific marker would be
      particularly useful in the examination of small specimens where there is not
      sufficient material for an extensive study of the hormonal expression. CDX2 is a
      transcription factor that has been recently proposed as a marker of intestinal
      adenocarcinomas. Our aim was to evaluate the immunohistochemical expression of
      CDX2 in normal tissues and in 184 formalin-fixed and paraffin-embedded ETs to
      verify whether it could be used to identify intestinal ETs with a high degree of
      sensitivity and specificity. Of these cases, 154 were primary tumors (99 GEP and
      55 non-GEP tumors), 101 were well-differentiated endocrine tumors, and 53 were
      poorly differentiated endocrine carcinomas (PDECs). Of the cases, 30 were
      metastases from differently located ETs. Nuclear CDX2 immunoreactivity was found
      in all EC-cells (serotonin-producing cells), in about 10% of G-cells (gastrin
      producing cells), in about 30% of GIP-cells (gastric inhibitory peptide cells)
      and in a few motilin-positive cells of the normal intestinal mucosa, while other
      gastrointestinal endocrine cell types were CDX2 negative. All midgut EC-cell
      tumors, their metastases, and two of three pancreatic EC-cell ETs were diffusely
      and intensely CDX2 positive. The other GEP ETs, their metastases, as well as the
      non-GEP ETs, were all CDX2 negative, with the exception of four PDECs, five
      gastrinomas and one pheochromocytoma, which were only focally positive. We
      conclude that CDX2 may be considered a sensitive and specific marker of midgut EC
      cells and EC-cell tumors, and its expression may be useful in the diagnosis of
      metastases from occult ETs.

PMID- 15517369
TI  - A proposal for diagnostically meaningful criteria to classify increased epidermal
      growth factor receptor and c-erbB-2 gene copy numbers in gastric carcinoma, based
      on correlation of fluorescence in situ hybridization and immunohistochemical
      measurements.
AB  - Amplification of the epidermal growth factor receptor (EGFR) and/or c-erbB-2
      oncogenes and overexpression of their proteins are detected in 30% of gastric
      carcinomas, but there are few reports regarding the correlation between gene
      amplification and protein overexpression. We examined the correlation between
      amplification of the EGFR and c-erbB-2 genes, detected using fluorescence in situ
      hybridization, and overexpression of their proteins, detected using
      immunohistochemistry, in formalin-fixed tissue sections of 54 surgically resected
      gastric carcinomas. A mean EGFR copy number per nucleus of four or more and an
      EGFR/chromosome 7 centromere (CEP7) ratio of 1.7 or more were each detected in 4
      specimens (7%). The sensitivity and specificity of both criteria for EGFR protein
      overexpression were 75% and 92%, respectively. A mean c-erbB-2 copy number per
      nucleus of 7.0 or more and a c-erbB-2/chromosome 17 centromere (CEP17) ratio of
      2.0 or more were detected in six (11%) and eight (15%) specimens, respectively.
      The sensitivity and specificity of the former criterion to c-erbB-2
      overexpression were 83% and 98%, respectively, while those of the latter were 63%
      and 98%. A mean EGFR gene copy number of 4.0 or more and/or an EGFR/CEP7 ratio of
      1.7 and a mean c-erbB-2 gene copy number of 7.0 or more and/or a c-erbB-2/CEP17
      ratio of 2.0 or more would be useful in defining increased EGFR and c-erbB-2 gene
      copy numbers, respectively, in gastric carcinomas.

PMID- 15517370
TI  - Expression and localization of membrane-type-1 matrix metalloproteinase, CD 44,
      and laminin-5gamma2 chain during colorectal carcinoma tumor progression.
AB  - Membrane-type-1 matrix metalloproteinase (MT1-MMP) is overexpressed in many
      malignant tumor tissues and would be involved in tumor-cell migration. Using dual
      immunofluorescence of frozen sections, this study examined the expression and
      localization of MT1-MMP and its interacting molecules, CD44 and laminin-5gamma2
      chain (LN-5gamma2) monomer, in 48 cases of colorectal tumors. Recent studies have
      shown that MT1-MMP, CD44 and LN-5gamma2 are direct downstream targets in the
      adenomatosis polyposis coli (APC)/beta-catenin (Wnt)-signaling pathway, which is
      upregulated in most colorectal epithelial tumors. MT1-MMP overexpression was
      observed in adenocarcinoma cases with moderate and/or less differentiation
      coinciding with CD44 downmodulation. Recent observations indicate that MT1-MMP
      overexpression disrupts tubulogenesis of MDCK cells in type-I collagen-rich
      tissues. Therefore, MT1-MMP overexpression might involve disturbances of
      neoplastic glandular structures during colorectal adenocarcinoma tumor
      progression. Intensity distribution analyses of images with dual
      immunofluorescence indicated that overexpressed MT1-MMP is closely associated
      with the enhanced expression of the LN-5gamma2 monomers at the invasive front of
      dedifferentiated tumor cells. Additionally, the graded expression of nuclear
      active beta-catenin was found in moderately differentiated and dedifferentiated
      areas of adenocarcinomas, where MT1-MMP overexpression was observed. Therefore,
      this study reveals that MT1-MMP might be a major effector of Wnt signaling in the
      late stage of colorectal carcinoma tumor progression.

PMID- 15517371
TI  - Juvenile rhesus monkeys have more colonic granulomas than adults after primary
      infection with Schistosoma mansoni.
AB  - Adults and children have differences in their susceptibility to schistosomiasis.
      Whether this age-dependent innate susceptibility influences parasite-caused
      granulomogenesis is difficult to assess in humans. Therefore, we exposed juvenile
      and adult female rhesus monkeys to primary infection with Schistosoma mansoni.
      Hepatic and intestinal granuloma formation was observed in both pre-pubescent and
      adult monkeys. Two distinct stages of granulomas were discerned, the exudative
      and the productive stage. In the intestine, more granulomas were generated in the
      colon than in the ileum. In contrast to the adult animals, the juvenile rhesus
      monkeys had higher numbers of colonic granulomas, these higher numbers being
      predominantly of the more advanced productive stage. Juvenile animals had a
      statistically non-significant increased worm burden. These results suggest that
      juvenile rhesus monkeys have a significantly more intense and advanced colonic
      response towards entrapped S. mansoni eggs after primary schistosome infections
      and, thereby, are more susceptible to parasite infection.

PMID- 15517372
TI  - Epithelioid and rhabdoid rhabdomyosarcoma in an adult patient: a diagnostic
      pitfall.

PMID- 15517373
TI  - Nonsecretory multiple myeloma with amyloidosis. A case report and review of the
      literature.
AB  - We report a case concerning a 49-year-old female patient with thoracic pain. X
      rays showed a single osteolytic lesion on the right seventh rib. The excision of
      the rib disclosed a plasmocytic plasmocytoma with extensive amyloidosis. Serum
      and urine protein electrophoresis were both negative for monoclonal gammopathy.
      Bone marrow biopsy showed that 80% of the marrow had been replaced by plasma
      cells. A diagnosis of nonsecretory multiple myeloma was made.
      Immunohistochemistry revealed amyloid light (AL) amyloidosis of kappa-light chain
      origin. The relationship between nonsecretory multiple myeloma and amyloidosis is
      discussed.

PMID- 15517374
TI  - Mucoepidermoid carcinoma of the palate composed exclusively of clear cells (clear
      cell variant).

PMID- 15517376
TI  - Can periventricular leucomalacia cause spastic diplegia in premature infants?

PMID- 15517377
TI  - Brain-Thyroid-Lung syndrome: a patient with a severe multi-system disorder due to
      a de novo mutation in the thyroid transcription factor 1 gene.
AB  - A 23-year-old man was diagnosed with pulmonary alveolar proteinosis at the age of
      11 months, and primary hypothyroidism gradually developed during infancy. He had
      delayed developmental milestones and severe hypotonia that evolved into non
      progressive chorea during childhood. He died from large cell lung carcinoma at
      the age of 23 years. A de novo heterozygous insertion mutation 859-860insC in the
      TITF-1 gene was demonstrated. CONCLUSION: TITF-1 gene mutations should be
      considered in paediatric and adult patients with unexplained (combinations of)
      chorea, mental retardation, primary hypothyroidism, and chronic lung disease.
      Introduction of a name for the disorder, e.g. Brain-Thyroid-Lung syndrome, would
      probably facilitate further recognition. Whether the TITF-1 gene mutation in this
      patient predisposed to the development of lung cancer remains speculative.

PMID- 15517378
TI  - Myelodysplastic features in an infant with cystic fibrosis presenting with
      anaemia, oedema and failure to thrive.

PMID- 15517379
TI  - Effect of childhood obesity and obesity-related cardiovascular risk factors on
      glomerular and tubular protein excretion.
AB  - There is increasing evidence that obesity may damage the kidney in otherwise
      healthy individuals. Our study investigated the effect of childhood obesity on
      urinary albumin and beta-2-microglobulin excretion, and the association of these
      with obesity-related cardiovascular risk factors. Random morning spot urine
      samples were collected from clinically healthy obese (n = 86; median age 12.9
      years, range 8.9-17.2 years; median weight 80.6 kg, range 46.1-136.8 kg; median
      body mass index 30.4 kg/m2, range 24.5-43.2 kg/m2) and normal weight children (n
      = 79; median age 13.5 years, range 10.7-14.9 years; median weight 51.0 kg, range
      27.3-72.5 kg; median body mass index 18.2 kg/m2, range 13.2-23.9 kg/m2). The
      obese children were examined for the presence of common obesity-related
      cardiovascular risk factors including hyperinsulinaemia, impaired glucose
      tolerance (IGT), dyslipidaemia, hypercholesterolaemia, and hypertension. Obese
      children had a significantly higher urinary albumin/creatinine ratio (U-ACR)
      (median 11.7 mg/g, interquartile range 12.9 mg/g versus median 9.0 mg/g,
      interquartile range 5.1 mg/g; P = 0.003) and urinary beta-2
      microglobulin/creatinine ratio (U-BMCR) (median 63.9 microg/g, interquartile
      range 34.7 microg/g versus median 34.6 microg/g, interquartile range 44.1
      microg/g; P < 0.001) than normal weight children. Among the obese children, the U
      ACR was associated with fasting hyperinsulinaemia, IGT, and hypercholesterolaemia
      (all P < 0.05), and significantly correlated with the fasting (r = 0.23, P <
      0.05) and 2-h (r = 0.37, P < 0.001) plasma glucose levels measured during an oral
      glucose tolerance test. Obese children with no more than one of the features of
      the metabolic syndrome had significantly lower U-ACRs than obese children with
      two or more features (median 10.4 mg/g, interquartile range 5.8 mg/g versus
      median 15.3 mg/g, interquartile range 14.9 mg/g; P < 0.05). CONCLUSION: According
      to our results, clinically healthy obese children have a higher degree of
      albuminuria and beta-2-microglobulinuria than normal weight children, indicating
      early renal glomerular and tubular dysfunction as a consequence of childhood
      obesity. The urinary albumin/creatinine ratio in the obese children was
      associated with certain metabolic derangements linked to obesity, and also with
      the clustering of features of the metabolic syndrome.

PMID- 15517380
TI  - Delta1-pyrroline-5-carboxylate synthase deficiency: neurodegeneration, cataracts
      and connective tissue manifestations combined with hyperammonaemia and reduced
      ornithine, citrulline, arginine and proline.
AB  - Delta1-pyrroline-5-carboxylate synthase (P5CS) catalyses the reduction of
      glutamate to Delta1-pyrroline-5-carboxylate, a critical step in the biosynthesis
      of proline, ornithine and arginine. Recently, we reported a newly recognised
      inborn error due to deficiency of P5CS in two sibs, one presenting at birth with
      hypotonia, dysmorphic signs, pes planus and clonic seizures. Both developed
      progressive neurodegeneration and peripheral neuropathy, joint laxity, skin
      hyperelasticity and bilateral subcapsular cataracts. Their metabolic phenotype
      includes mild hyperammonaemia, hypo-ornithinaemia, hypocitrullinaemia, hypo
      argininaemia and hypoprolinaemia. Incorporation of 3H-proline into protein was
      deficient in fibroblasts incubated with 3H-glutamate. Both patients are
      homozygous for the missense mutation R84Q in P5CS. Here, we describe the clinical
      phenotype of the sibs in detail and show that a relative deficiency of urea cycle
      intermediates (ornithine, citrulline and arginine) during fasting periods results
      in a paradoxical hyperammonaemia. Furthermore, we show the results of ornithine
      loading tests and indirect enzyme studies corroborating the biological
      significance of the defect in P5CS in vivo. CONCLUSION: The metabolic phenotype
      of Delta1-pyrroline-5-carboxylate synthase deficiency is easily missed. The
      combination of low levels of ornithine, citrulline, arginine and proline plus a
      tendency to hyperammonaemia or one of the above together with a clinical
      phenotype of neurodegeneration with peripheral neuropathy and/or cataracts and
      connective tissue manifestations should suggest this disorder. Early recognition
      would allow a therapeutic trial with citrulline and proline.

PMID- 15517381
TI  - Effective parenteral clodronate treatment of a child with severe juvenile
      idiopathic osteoporosis.
AB  - We report on an 8 years and 3 months old boy with severe idiopathic juvenile
      osteoporosis (IJO). Clinical features included multiple fractures, especially of
      the vertebrae, and neurological symptoms. Biological studies showed non
      parathyroid hormone-mediated excessive bone resorption and massive urinary
      calcium loss. Although IJO is usually a self-limiting condition after puberty,
      the severity of our patient's manifestations required therapeutic intervention.
      Clodronate (dichloromethylene-bisphosphonate) was administered parenterally every
      3 months for a period of 2 years. Dramatic clinical and biochemical improvement
      was noted within 2 weeks. All parameters of bone resorption normalised and no new
      fractures occurred. After 6 months of treatment, radiological improvement with
      healing of fractures and rebuilding of the vertebral plates was documented. Bone
      mineral density increased to normal within 1 year and growth velocity was
      accelerated. After 2 years, treatment was stopped at the age of 10 years and 3
      months. One year later, back pain and increasing pain in the knee region
      recurred. A tibial fracture was evident and, again, bone mineral density was far
      below normal. Bisphosphonate medication was reinstituted leading to rapid
      improvement. No side-effects were observed. CONCLUSION: Parenteral clodronate
      therapy is effective in managing severe idiopathic juvenile osteoporosis.

PMID- 15517382
TI  - Note on the feeding habits of Opisthogonimus lecithonotus (Trematoda, Digenea,
      Plagiorchiidae).
AB  - The presence of snake's blood inside the alimentary canal of the species
      Opisthogonimus lecithonotus (Trematoda, Digenea, Plagiorchiidae) collected from
      the mouth of Bothrops moojeni (Serpentes, Viperidae) is reported. The
      implications of this observation to the host snake are discussed.

PMID- 15517383
TI  - Ultrastructure of the spermatozoon of the anoplocephalid cestode Gallegoides
      arfaai (Mobedi and Ghadirian, 1977) Tenora and Mas-Coma, 1978, an intestinal
      parasite of the wood mouse (Apodemus sylvaticus Linnaeus, 1758).
AB  - The present work involves an ultrastructural study of the mature spermatozoon of
      the anoplocephalid cestode Gallegoides arfaai (Mobedi and Ghadirian, 1977) Tenora
      and Mas-Coma, 1978, obtained from the small intestine of naturally infected wood
      mice, Apodemus sylvaticus Linnaeus, 1758 (Rodentia, Muridae). The mature
      spermatozoon of G. arfaai is a filiform cell, tapered at both ends and lacking
      mitochondria. It is characterized by the presence of a 1,000-nm-long apical cone
      and two 140-nm-thick crest-like bodies in its anterior extremity. The axoneme, of
      the 9 + '1' trepaxonematan pattern, lacks a periaxonemal sheath, and
      disorganization occurs at the level of the nuclear region of the sperm cell. The
      cortical microtubules form two to four fields according to the different regions
      of the male gamete. They are twisted at an angle of about 35 degrees , becoming
      parallel towards the posterior extremity of spermatozoon. The nucleus, spiralled
      around the axoneme, shows an irregular shape in both longitudinal and cross
      sections. Numerous electron-dense granules were observed, which transform into an
      electron-dense material in the posterior extremity of the cell. Moreover, we
      describe for the first time the total length of the anterior region of sperm
      containing the helical crest-like bodies. This anterior extremity measures around
      15 mum and presents two helical crest-like bodies of different lengths that
      describe 13-14 turns around the sperm body. Our ultrastructural results on the G.
      arfaai spermatozoon are compared with the ultrastructural organization of the
      spermatozoa of other previously studied species, with particular emphasis on the
      anoplocephalids.

PMID- 15517384
TI  - Sarcocystis neurona major surface antigen gene 1 (SAG1) shows evidence of having
      evolved under positive selection pressure.
AB  - The major surface antigen gene 1 (SAG1) is conserved among members of
      Sarcocystidae and may play an important role in parasite pathogenesis.
      Additionally, generation and selection of different antigenic variants of SAG1
      has the potential for inclusion in a subunit vaccine or in the development of a
      diagnostic assay. In this study, patterns of nucleotide polymorphism were used to
      test the hypothesis that natural selection promotes diversity in different parts
      of SAG1 of Sarcocystis neurona. Nucleotide and amino acid sequence analysis of
      SAG1 from multiple S. neurona isolates identified two alleles. Sequences were
      identical intra-allele and highly divergent inter-alleles. Also, phylogenetic
      reconstruction showed sequences clustering into two clades. Tajima's and Fu and
      Li's neutrality tests indicated that selection is more likely to be acting on
      SAG1. Moreover, a sliding window analysis based on the ratio of silent
      substitutions to amino acid replacements provided strong evidence that two short
      segments in the central and 3' domain of SAG1 have been under positive selection
      in the divergence of the two alleles, suggesting that it may be important for the
      evasion of host immune responses and would be a suitable target for vaccine
      development.

PMID- 15517385
TI  - Ultrastructural characters of the spermatozoon of the cestode Corallobothrium
      solidum Fritsch, 1886 (Cestoda: Proteocephalidea), a parasite of the electric
      catfish Malapterurus electricus.
AB  - The fine structure of the mature spermatozoon of the corallobothriine tapeworm
      Corallobothrium solidum Fritsch, 1886 (Cestoda: Proteocephalidea) from the
      electric catfish Malapterurus electricus from the Nile River in Egypt was studied
      by transmission electron microscopy for the first time. The filiform spermatozoon
      of C. solidum contains two axonemes of unequal length and a typical 9 + "1"
      trepaxonematan pattern. A single helicoidal crested body (30-200 nm thick) is
      localized at the anterior extremity of the gamete. The cortical microtubules line
      the periphery of the cell, largely parallel to the long axis of the spermatozoon
      and exhibiting signs of twisting at the beginning of region II. The nucleus, in
      the form of an electron-dense (largely in gametes of testes) and/or fibrous cord
      (largely in gametes from male reproductive ducts and seminal vesicle), coils in a
      spiral through the middle part (region III) of the spermatozoon. The cytoplasm
      contains electron-dense granules in regions II, III and partly in region IV. The
      cytoplasm of some spermatozoa exhibits an apparently higher electron-density at
      the end of the nucleated region (III), and continuously toward the middle part of
      region IV. The anterior and posterior extremities of the spermatozoa have a
      single axoneme. The ultrastructural features of the mature spermatozoon of C.
      solidum mostly coincide with those of the spermatozoon of other
      proteocephalideans, especially the gangesiine Electrotaenia malopteruri
      parasitizing the same host.

PMID- 15517386
TI  - Epidemiological survey of the prevalence of parasites among children in Khan
      Younis governorate, Palestine.
AB  - The prevalence of intestinal parasites was determined for 1,370 children in Khan
      Younis Governorate, Gaza Strip. The age of the children ranged from 6 to 11
      years. For stool samples, inspection, direct smear microscopy, flotation and
      sedimentation techniques were used. The general prevalence of intestinal
      parasites was 34.2%. Different types of intestinal parasites were detected during
      this survey: Ascaris lumbricoides seemed to be the most common parasite (12.8%),
      whereas Giardia lamblia had a prevalence of 8.0%, Entamoeba histolytica 7.0%,
      Entamoeba coli 3.6%, Trichuris trichiura 1.6% and Hymenolepis nana 1.0%. The
      prevalence of enterobiasis was determined using a scotch tape preparation. A
      total of 20.9% of the children examined were infected and there was sex variation
      in the prevalence of enterobiasis.

PMID- 15517387
TI  - The effect of topoisomerase II inhibitors on the kinetoplast ultrastructure.
AB  - Topoisomerases from trypanosomatids play key functions in the replication and
      organization of kinetoplast DNA (kDNA). Hence, they are considered as potential
      targets for anti-parasite drugs. In this paper, the effect of topoisomerase II
      inhibitors, such as nalidixic acid, novobiocin and etoposide, on the
      ultrastructure of trypanosomatids that present distinct kDNA arrangements was
      evaluated. Prokaryotic topoisomerase II inhibitors were more effective on growth
      arrest and ultrastructure changes than etoposide, a eukaryotic topoisomerase II
      inhibitor. With the exception of novobiocin, drug concentrations which inhibited
      cell proliferation also promoted kinetoplast ultrastructure alterations,
      including the redistribution of topoisomerase II. The data reinforce the concept
      that prokaryotic topoisomerase II inhibitors may offer greater selectivity in
      drug therapy of trypanosomatid infections.

PMID- 15517388
TI  - Response of two isolates of Fasciola hepatica to treatment with triclabendazole
      in vivo and in vitro.
AB  - In this study, the susceptibility of two isolates of Fasciola hepatica--the
      Fairhurst and Oberon isolates--to treatment with triclabendazole was
      investigated, both in vivo and in vitro. The Fairhurst isolate originated in
      England, but has since been maintained in Australia; the Oberon isolate
      originated in Australia. Triclabendazole had a very high efficacy against the
      Fairhurst isolate. In sheep (dose: 10 mg/kg), the efficacy ranged from 78.4% at 2
      weeks post-infection to 98.5% at 6 weeks post-infection. In cattle (dose: 12
      mg/kg) efficacy was 89% at 2 weeks post-infection and 100% at 12 weeks. In
      contrast, against the Oberon isolate, triclabendazole had 0% efficacy against 2
      week-old flukes in sheep (dose: 10 mg/kg) and 5% against 4-week-old flukes.
      Surface changes to flukes of the two isolates were assessed by scanning electron
      microscopy following treatment in vitro for 24 h in triclabendazole sulphoxide
      (15 and 50 microg/ml). Disruption took the form of blebbing, swelling and
      furrowing of the tegument and was greater in the Fairhurst than the Oberon
      isolate. Surface changes generally were more severe in the anterior than
      posterior region of the fluke and the dorsal surface was also consistently more
      severely affected than the ventral surface. Disruption was more severe at the
      higher drug concentration for both isolates. The morphological data is consistent
      with the efficacy data, which indicates that the Fairhurst isolate of F. hepatica
      is susceptible to triclabendazole treatment, whilst the Oberon isolate is
      refractory.

PMID- 15517390
TI  - Comparative profiling of lipid-soluble antioxidants and transcripts reveals two
      phases of photo-oxidative stress in a xanthophyll-deficient mutant of
      Chlamydomonas reinhardtii.
AB  - Excess light can impose severe oxidative stress on photosynthetic organisms. We
      have characterized high-light responses in wild-type Chlamydomonas reinhardtii
      and in the npq1 lor1 double mutant. The npq1 lor1 strain lacks two
      photoprotective carotenoids, lutein and zeaxanthin, and experiences acute photo
      oxidative stress upon exposure to excess light. To examine the ability of npq1
      lor1 cells to respond to photo-oxidative stress, we measured changes in lipid
      soluble antioxidants following a shift from low light to high light in the wild
      type and the double mutant. The size of the xanthophyll cycle pool increased in
      both the wild type and mutant during the first 6 h of exposure to high light
      levels, but then decreased in the mutant during photo-oxidative bleaching. The
      level of alpha-tocopherol (vitamin E) was constant in the wild type and mutant
      during the first 6 h; then it increased by three-fold in the wild type but
      declined in npq1 lor1 cells. We also used cDNA microarrays and RNA gel-blot
      analysis to monitor differences in gene expression. Both strains showed an
      initial light-stress response in the form of a transient increase in expression
      of (1) GPXH, a glutathione peroxidase gene that has been shown to respond
      specifically to singlet oxygen and lipid peroxidation; (2) SMT1, a gene for a
      putative sterol C-methyltransferase; and (3) LI818r, a stress-responsive member
      of the light-harvesting complex superfamily. These transient changes in gene
      expression in high light were followed by a second series of changes in npq1
      lor1, coincident with declines in lipid-soluble antioxidants but preceding
      detectable photo-oxidative damage to proteins and lipids. Thus, the response of
      npq1 lor1 to high light is unexpectedly complex, with initial changes in lipid
      soluble antioxidants and RNA levels that are associated with acclimation in the
      wild type and a second wave of changes that accompanies photo-oxidative
      bleaching.

PMID- 15517391
TI  - TamA interacts with LeuB, the homologue of Saccharomyces cerevisiae Leu3p, to
      regulate gdhA expression in Aspergillus nidulans.
AB  - Previous studies have shown that expression of the gdhA gene, encoding NADP
      linked glutamate dehydrogenase (NADP-GDH), in Aspergillus nidulans is regulated
      by the major nitrogen regulatory protein AreA and its co-activator TamA. We show
      here that loss of TamA function has a more severe effect on the levels of gdhA
      expression than loss of AreA function. Using TamA as the bait in a yeast two
      hybrid screen, we have identified a second protein that interacts with TamA.
      Sequencing analysis and functional studies have shown that this protein,
      designated LeuB, is a transcriptional activator with similar function to the
      homologous Leu3p of Saccharomyces cerevisiae. Inactivation of leuB revealed that
      this gene is involved in the regulation of gdhA, and an areA; leuB double mutant
      was shown to have similar NADP-GDH levels to a tamA single mutant. The
      requirement for TamA function to promote gdhA expression is likely to be due to
      its dual interaction with AreA and LeuB.

PMID- 15517393
TI  - Hereditary hemorrhagic telangiectasia: ENG and ALK-1 mutations in Dutch patients.
AB  - Hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber disease is an
      autosomal dominant disorder characterized by an aberrant vascular development.
      The resulting vascular lesions range from smaller mucocutaneous telangiectases to
      large visceral arteriovenous malformations, especially in the skin, lung,
      gastrointestinal tract and the brain. Mutations in the genes encoding endoglin
      (ENG, chromosome 9q34) and activin A receptor type-like kinase 1 (ALK-1, also
      named ACVRL1, chromosome 12q13) are associated with HHT1 and HHT2, respectively.
      We report here on the genetic and molecular heterogeneity found in the HHT
      population in the Netherlands. Probands of 104 apparently unrelated families were
      studied and we performed sequence analysis on both the ENG gene and ALK-1 gene.
      In most of the probands, we found a mutation in one of the two genes: 53% in the
      ENG gene and 40% in the ALK-1 gene. In 7% of the families no ENG or ALK1 mutation
      was found. The mutations detected were deletions, insertions, nonsense, missense
      and splice site mutations. The majority were novel mutations.

PMID- 15517392
TI  - Characterization of a T-DNA insertion mutant for the protein import receptor
      atToc33 from chloroplasts.
AB  - In Arabidopsis thaliana, the Toc34 receptor component of the chloroplast import
      machinery is encoded by two independent but highly homologous genes, atToc33 and
      atToc34. We have isolated a T-DNA insertion mutant of atToc33 which is
      characterized by a pale phenotype, due to reductions in the levels of
      photosynthetic pigments, and alterations in protein composition. The latter
      involve not only chloroplast proteins but also some cytosolic polypeptides,
      including 14-3-3 proteins which, among other functions, have been proposed to be
      cytosolic targeting factors for nucleus-encoded chloroplast proteins. Within the
      chloroplast, many, though not all, proteins of the photosynthetic apparatus, as
      well as proteins not directly involved in photosynthesis, are found in
      significantly reduced amounts in the mutant. However, the accumulation of other
      chloroplast proteins is unaffected. This suggests that the atToc33 receptor is
      responsible for the import of a specific subset of nucleus-encoded chloroplast
      proteins. Supporting evidence for this conclusion was obtained by antisense
      repression of the atToc34 gene in the atToc33 mutant, which results in an
      exacerbation of the phenotype.

PMID- 15517394
TI  - RGD-containing fibrillin-1 fragments upregulate matrix metalloproteinase
      expression in cell culture: a potential factor in the pathogenesis of the Marfan
      syndrome.
AB  - The Marfan syndrome (MFS), a relatively common autosomal dominant disorder of
      connective tissue, is caused by mutations in the gene for fibrillin-1 (FBN1).
      Fibrillin-1 is the main component of the 10- to 12-nm microfibrils that together
      with elastin form elastic fibers found in tissues such as the aortic media.
      Recently, FBN1 mutations have been shown to increase the susceptibility of
      fibrillin-1 to proteolysis in vitro, and other findings suggest that up
      regulation of matrix metalloproteinases (MMP), as well as fragmentation of
      microfibrils, could play a role in the pathogenesis of MFS. In the present work,
      we have investigated the influence of fibrillin-1 fragments on the expression of
      MMP-1, MMP-2, and MMP-3 in a cell culture system. Cultured human dermal
      fibroblasts were incubated with several different recombinant fibrillin-1
      fragments. The expression level of MMP-1, MMP-2, and MMP-3, was determined by
      quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), and the
      concentration of the corresponding proteins was estimated by quantitative Western
      blotting. Our results establish that treatment of cultured human dermal
      fibroblasts with recombinant fibrillin-1 fragments containing the arginine
      glycine-aspartic acid (RGD) integrin-binding motif of fibrillin-1 induces up
      regulation of MMP-1 and MMP-3. A similar effect was seen upon stimulation with a
      synthetic RGD peptide. The expression of MMP-2 was not influenced by treatment.
      Our results suggest the possibility that fibrillin fragments could themselves
      have pathogenic effects by leading to up-regulation of MMPs, which in turn may be
      involved in the progressive breakdown of microfibrils thought to play a role in
      MFS.

PMID- 15517395
TI  - Confirmation and refinement of a genetic locus of congenital motor nystagmus in
      Xq26.3-q27.1 in a Chinese family.
AB  - Congenital motor nystagmus (CMN), a subtype of nystagmus, may reduce vision or be
      associated with other, more serious, conditions that limit vision. The genetic
      basis for CMN is still unknown. To identify a locus for CMN, genotyping and
      linkage analysis were performed in 22 individuals from a Chinese family with X
      linked CMN using markers from X chromosome. The maximum LOD score obtained for
      microsatellite maker DXS1192 linked the CMN locus in this family to Xq. By
      haplotype construction the locus for CMN was finally localized to an
      approximately 4.4-cM region at chromosome Xq26.3-q27.1. The SLC9A6 and FGF13
      genes in this region, were selected and screened for mutation in this family, but
      no mutation was detected.

PMID- 15517397
TI  - Haemopoietic progenitors in the adult mouse omentum: permanent production of B
      lymphocytes and monocytes.
AB  - The coelome-associated lympho-myeloid tissues, including the omentum, are derived
      from early embryo haemopoietic tissue of the splanchnopleura, and produce B
      lymphocytes and macrophages. They are reactive in pathologies involving coelomic
      cavities, in which they can expand in situ the cells of inflammatory infiltrates.
      We have addressed the question of the role of the adult omentum in permanent
      basal production of early lymphopoietic progenitors (pro-B/pre-B cells), through
      characterisation of omentum cells ex vivo, and study of their in vitro
      differentiation. We have shown that the murine omentum produces early
      haemopoietic progenitors throughout life, including B-cell progenitors prior to
      the Ig gene recombination expressing RAG-1 and lambda5, as well as macrophages.
      Their production is stroma-dependent. The omentum stroma can supply in vitro the
      cytokines (SDF-1alpha, Flt3 ligand and IL-7) and the molecular environment
      required for generation of these two cell lineages. Omentum haemopoietic
      progenitors are similar to those observed in foetal blood cell production, rather
      than to progenitors found in the adult haemopoietic tissue in the bone marrow--in
      terms of phenotype expression and differentiation capacity. We conclude that a
      primitive pattern of haemopoiesis observed in the early embryo is permanently
      preserved and functional in the adult omentum, providing production of cells
      engaged in nonspecific protection of abdominal intestinal tissue and of the
      coelomic cavity.

PMID- 15517396
TI  - Linkage disequilibrium mapping in the Newfoundland population: a re-evaluation of
      the refinement of the Bardet-Biedl syndrome 1 critical interval.
AB  - Genetically isolated populations, such as Newfoundland, have contributed greatly
      to the identification of disease-causing genes. A linkage disequilibrium (LD)
      study involving six Newfoundland families predicted a critical interval for
      Bardet-Biedl syndrome 1 (BBS1) (Young et al. in Am J Hum Genet 65:1680-1687,
      1999), but the subsequent identification of BBS1 revealed that it lies outside
      this region. This suggested that either there is another gene responsible for BBS
      in these families or the Newfoundland population may not be ideal for LD studies.
      We screened these six Newfoundland families for mutations in BBS1 and found that
      affected individuals in five of them were homozygous for the same M390R mutation.
      There was no evidence for any BBS1 mutation in the affected individual in the
      sixth family. Therefore, one of the criteria for LD mapping was not met; namely,
      there should be a single disease-causing allele in the population. Haplotype
      analysis of unaffected individuals from south-west Newfoundland and English BBS1
      patients homozygous for M390R, revealed that a second criterion for LD mapping
      was violated. The M390R mutation occurred in a common haplotype and both of these
      chromosomes, the ancestral wild-type and disease-causing haplotypes, were
      introduced to Newfoundland and spread by a founder effect. Moreover, it was found
      that disease-associated alleles occurred at relatively high frequencies in normal
      haplotypes and this probably accounted for the incorrect prediction in the
      previous LD study. Knowing the amount of genetic variation and its distribution
      in the Newfoundland population would be useful to maximize its potential for
      mapping hereditary disorders.

PMID- 15517398
TI  - Ontogeny of the antennal glands in the crayfish Astacus leptodactylus (Crustacea,
      Decapoda): anatomical and cell differentiation.
AB  - The ontogeny of the antennal glands was studied during the embryonic and post
      embryonic development of Astacus leptodactylus. The future glands arising from
      undifferentiated columnar cells were detectable at the metanauplius stage EI 150
      microm (EI: eye index; approximately 440 microm at hatching). The tubule and
      labyrinth differentiated in embryos at EI 190 microm, and the bladder and
      coelomosac at EI 250 microm. At EI 350 microm, the tubule lengthened and divided
      into proximal and distal sub-regions. In later stages, the gland retained the
      same morpho-anatomy but the differentiation and size of each part increased. The
      cells of the coelomosac displayed the cytological features of podocytes in late
      embryonic development at EI 440 microm. Only small apical microvilli and a few
      mitochondria were observable in the labyrinth cells at EI 250 microm; by EI 440
      microm, these cells presented well-shaped apical microvilli, formed bodies, basal
      infoldings and mitochondria. In the cells of the tubules and bladder,
      mitochondria and basal infoldings occurred at EI 440 microm and EI 250 microm,
      respectively. The differentiation of the tubules and bladder cells suggested that
      they were involved in active transport at EI 440 microm. Following hatching, the
      differentiation of the cells and the size of the glands increased. The ontogeny
      of the antennal glands thus starts in early embryos, the specific cellular
      functional features being differentiated in the various parts of the glands by EI
      440 microm. The antennal glands are probably functional just before hatching,
      i.e., before the juveniles are confronted with the low osmolality of freshwater.

PMID- 15517399
TI  - Ontogeny of the antennal glands in the crayfish Astacus leptodactylus (Crustacea,
      Decapoda): immunolocalization of Na+,K+-ATPase.
AB  - The involvement of the antennal urinary glands in the ontogeny of osmoregulatory
      functions was investigated during the development of Astacus leptodactylus by
      measurements of hemolymph and urine osmolality in juvenile and adult crayfish and
      by the immunodetection of the enzyme Na+,K+-ATPase. In stage II juveniles, 1-year
      old juveniles, and adults, all of which were maintained in freshwater, urine was
      significantly hypotonic to hemolymph. In adults, chloride and sodium
      concentrations were much lower in urine than in hemolymph. During embryonic
      development, Na+,K+-ATPase was detected by immunocytochemistry in ionocytes
      lining the tubule and the bladder, at an eye index (EI) of 220-250 microm, and in
      the labyrinth, at EI 350 microm. In all regions, immunofluorescence was mainly
      located at the basolateral side of the cells. No immunofluorescence was detected
      at any stage in the coelomosac. In late embryonic stages (EI 410-440 microm), in
      stage I juveniles, and in adults, strong positive immunofluorescence was found
      from the labyrinth up to and including the bladder. These results show that, as
      early as hatching, juvenile crayfish are able to produce dilute urine hypotonic
      to hemolymph. This ability originates from the presence of Na+,K+-ATPase in ion
      transporting cells located in the labyrinth, the tubule, and the bladder of the
      antennal glands and constitutes one of the main adaptations of crayfish to
      freshwater.

PMID- 15517400
TI  - Cellular localisation of insulin-like growth factor binding protein-2 (IGFBP-2)
      during development of the marine fish, Sparus aurata.
AB  - The spatial localisation of insulin-like growth-factor-binding protein-2 (IGFBP
      2) and its mRNA was investigated during larval and post-larval developmental
      stages of the gilthead seabream ( Sparus aurata) by immunohistochemistry and in
      situ hybridisation with specific antisera and riboprobes. During larval
      development, immunoreactivity was found in skin, muscle, gills, pharynx,
      intestine, liver and olfactory epithelium. After metamorphosis, immunoreactivity
      was found in the oesophageal epithelium (the strongest reaction) and in red
      skeletal muscle, heart muscle, the thymus and the epithelium of renal tubules. In
      the adult, immunostaining with IGFBP-2 antibody was also found in the saccus
      vasculosus, ovary and testis. IGFBP-2 mRNA was detected by in situ hybridisation
      mainly in the intestine, skeletal musculature and ovary. These results show that
      IGFBP-2 protein and mRNA are expressed in a variety of seabream tissues,
      suggesting that IGFBP-2 regulates the actions of IGFs on these tissues during
      development and growth.

PMID- 15517401
TI  - Expression of ephrin-A ligands and EphA receptors in the developing mouse tooth
      and its supporting tissues.
AB  - Ephrins are cell-membrane-bound ligands for Eph receptor tyrosine kinases and
      regulate a variety of developmental processes. In order to investigate the
      potential roles of the ephrin-Eph system in tooth formation, we studied the
      cellular mRNA expression of Ephrin-A1-A5 and EphA2, EphA3, EphA4, EphA7, and
      EphA8 receptors during embryonic histomorphogenesis of the mouse first molar
      (embryonic days 11.5-18.5). Ephrin-A1, ephrin-A5, EphA2, EphA3, EphA4, and EphA7
      were expressed in the tooth germ at the epithelial thickening stage, and later,
      ephrin-A1, ephrin-A5, EphA2, EphA4, and EphA7 showed distinct expression patterns
      in the enamel organ undergoing epithelial folding morphogenesis. Prior to birth,
      ephrin-A1, ephrin-A5, EphA2, and EphA4 transcripts were present in the cuspal
      area of the dental papilla including the preodontoblasts. In addition, ephrin-A1
      and ephrin-A5 were seen in the forming blood vessels and alveolar bone,
      respectively. In contrast, ephrin-A2, ephrin-A3, and ephrin-A4 showed ubiquitous
      expression during odontogenesis, whereas EphA8 transcripts were not observed.
      During dental trigeminal axon pathfinding (embryonic days 12.5-13.5), ephrin-A2,
      ephrin-A4, and ephrin-A5 were evenly distributed in the trigeminal ganglion,
      whereas EphA7 was expressed in a subset of ganglion cells. These results suggest
      regulatory roles for ephrin-A/EphA signaling in the formation of the tooth organ
      proper and its supporting tissues.

PMID- 15517402
TI  - MHC class II antigen-expressing cells in cardiac ganglia of the rat.
AB  - Cardiac ganglia develop destructive ganglionitis in chronic Chagas' disease and
      rheumatic heart disease. This ganglionitis is associated with periganglionic
      infiltrations and is suspected of developing secondary to epicardial
      inflammation. If so, it would be expected that cardiac ganglia (1) are equipped
      with an inventory of immune competent cells allowing the initiation of
      inflammatory processes, and (2) are not effectively protected from the milieu of
      the surrounding tissue by metabolically active diffusion barriers. These problems
      were addressed in specified pathogen-free rats by electron microscopy and
      immunohistochemistry with markers for dendritic cells, monocytes/macrophages, and
      perineurial barriers. In contrast to nerve fascicles, cardiac ganglia are only
      partially enveloped by perineurial cells. Inside the ganglia, ramified cells with
      major histocompatibility complex class II antigen (reacting with monoclonal
      antibody OX6) on their surface and exhibiting an ultrastructure typical of
      dendritic cells are numerous, comprising nearly 5% of all cells within ganglia.
      The ratio of the number of these cells to that of neurons is 1:2. Cells reacting
      with monoclonal antibodies ED1 and ED2, markers for monocytes/macrophages,
      constitute 1.8% and 1.6% of the ganglionic cell population, respectively. Such
      cells are less frequent in the cervical trunk of the vagus nerve. Thus, the
      inventory of immune competent cells in rat cardiac ganglia is consistent with the
      view that the abundance of antigen-presenting cells correlates with the
      permeability of the barriers providing protection from blood-borne and tissue
      borne factors.

PMID- 15517403
TI  - Developmental expression patterns and regulation of connexins in the mouse
      mammary gland: expression of connexin30 in lactogenesis.
AB  - The mammary gland reaches a fully differentiated phenotype at lactation, a stage
      characterized by the abundant expression of beta-casein. We have investigated the
      expression and regulation of gap junction proteins (connexins, Cx) during the
      various developmental stages of mouse mammary gland. Immunohistochemical
      analysis, with specific antibodies, reveals that Cx26 and Cx32 are expressed and
      confined to the cell borders of luminal epithelial cells in all developmental
      stages of the gland. Cx26 and Cx32 expression, at the mRNA and protein levels,
      increases in pregnancy and peaks in lactation. Whereas Cx43 mRNA decreases in
      pregnancy and lactation, the functional activity of Cx43 protein, which has been
      localized to myoepithelial cells, is regulated (through phosphorylation) during
      pregnancy and peaks during lactation. Cx30 mRNA and proteins have, for the first
      time, been detected in mammary gland epithelia. Using reverse
      transcription/polymerase chain reaction and sequencing techniques, we show that
      Cx30 is abundant in pregnant and lactating mammary gland. Cx30 protein levels
      have not been detected in the mammary gland prior to day 15 of pregnancy, whereas
      maximum expression occurs at the onset of lactation. In mouse mammary cells in
      culture, Cx30 is epithelial-cell-specific and is induced by lactogenic hormones.
      These data identify a novel player in mammary differentiation and suggest a
      potential role for Cx30 in the fully differentiated gland.

PMID- 15517404
TI  - Periosteum stimulates subchondral bone densification in autologous chondrocyte
      transplantation in a sheep model.
AB  - In this sheep study, we have tested the hypothesis that an osteogenic response is
      triggered in the subchondral bone by periosteum implanted in full thickness
      cartilage defects and can be prevented by replacing the periosteum by a cell-free
      collagen type I/III membrane. Two 7-mm diameter osteochondral defects were made
      in the trochlea groove and in the medial femoral condyle of one of the knees in
      each of 15 adult sheep. The animals were divided into three groups (n=5): a
      control group with untreated cartilage defects, a group treated with autologous
      chondrocyte transplantation (ACT) and periosteum, and a group treated with ACT in
      combination with a collagen I/III membrane cover. Histological examination was
      performed 1 year later. The optical density of the subchondral bone in the
      histological sections was measured with digital imaging software. There was a
      dramatic, statistically significant (P<0.0001; power=1) increase in bone density
      of 45%-70% under defects that were treated with the periosteal cover, compared
      with the collagen membrane and control groups, which displayed the same bone
      density. There was no difference in the cartilaginous reparative tissue in the
      defects in the three groups. Periosteum thus stimulates the remodelling process
      in subchondral bone. Stiffening of the subchondral bone can lead to degeneration
      of the overlying reparative cartilaginous tissue because of an increase in the
      mechanical stress in the tissue. These findings warrant evaluation of subchondral
      bone changes in patients treated by ACT and the correlation of these changes with
      clinical outcome.

PMID- 15517406
TI  - Old pythons stay fit; effects of haematozoan infections on life history traits of
      a large tropical predator.
AB  - We document the impact of blood parasite infections caused by Hepatozoon sp. on
      water python (Liasis fuscus) life history traits such as growth rates, condition,
      reproductive output and survival. Individual snakes maintained similar among-year
      parasite loads. Hepatozoon infections affected python growth rate, i.e. snakes
      suffering from high infection levels exhibited significantly slower growth
      compared to individuals with low parasite loads. Our results suggest that the
      parasites also affected the pythons' nutritional status (condition), as snakes
      with low condition scores suffered from higher parasite infection levels than
      snakes with high scores. Furthermore, our data suggest that parasitaemia may
      affect female reproductive output, as reproductive female pythons harboured lower
      parasite loads compared to non-reproductive adult females. High levels of
      parasite infections also affected juvenile python survival, as recaptured snakes
      harboured significantly lower parasite loads compared to non-recaptured yearling
      pythons. In our study area, water python have very few natural predators and,
      hence, experience low mortality rates and commonly reach an age of >15 years. In
      contrast to results obtained in other studies, parasite loads in larger/older
      pythons were lower compared to younger snakes, suggesting that only snakes
      harbouring lower levels of parasitaemia were able to survive to old age. We
      suggest that a possible cause for the opposing results regarding parasite
      prevalence and host age may be due to different levels of extrinsic mortality
      rates and longevity. Long-lived organisms, such as water pythons, may invest
      relatively more into crucial self-maintenance functions such as parasite defence,
      compared to short-lived organisms.

PMID- 15517405
TI  - Effects of light availability versus hydraulic constraints on stomatal responses
      within a crown of silver birch.
AB  - Responses of leaf conductance (gL) to variation in photosynthetic photon flux
      density (QP), leaf-to-air vapour pressure difference (VPD), bulk leaf water
      potential (Psi(x)), and total hydraulic conductance (GT) were examined in silver
      birch (Betula pendula Roth) with respect to leaf position in the crown. To reduce
      limitations caused by insufficient water supply or low light availability,
      experiments were also performed with branchlets cut from two different canopy
      layers. The intact upper-canopy leaves demonstrated 1.8-2.0 times higher
      (P<0.001) daily maxima of gL compared with the lower-canopy leaves growing in the
      shadow of upper branches. In the morning, gL in the shade foliage was primarily
      constrained by low light availability, in the afternoon, by limited water supply.
      Leaf conductance decreased when Psi(x) fell below certain values around midday,
      while the sun foliage experienced greater negative water potentials than the
      shade foliage. Midday stomatal openness was controlled by leaf water status and
      temperature, rather than by transpiration rate (E) via the feedforward mechanism.
      Mean GT was 1.7 times higher (P<0.001) for the upper-canopy foliage compared to
      that of the lower canopy. At least 34-39% of the total resistance to the water
      flow from soil up to the shade foliage, and 54% up to the sun foliage, resided in
      30-cm distal parts of the branches. Artificial reduction of hydraulic constraints
      raised Psi(x) and made gL less sensitive to changes in both atmospheric and plant
      factors. Improved water supply increased gL and E in the lower-canopy foliage,
      but not in the upper-canopy foliage. The results support the idea that leaves in
      the lower canopy are hydraulically more constrained than in the upper canopy.

PMID- 15517407
TI  - Quality or quantity: the direct and indirect effects of host plants on herbivores
      and their natural enemies.
AB  - Resource quality (plant nitrogen) and resource quantity (plant density) have
      often been argued to be among the most important factors influencing herbivore
      densities. A difficulty inherent in the studies that manipulate resource quality,
      by changing nutrient levels, is that resource quantity can be influenced
      simultaneously, i.e. fertilized plants grow more. In this study we disentangled
      the potentially confounding effects of plant quality and quantity on herbivore
      trophic dynamics by separately manipulating nutrients and plant density, while
      simultaneously reducing pressure from natural enemies (parasitoids) in a fully
      factorial design. Plant quality of the sea oxeye daisy, Borrichia frutescens, a
      common coastal species in Florida, was manipulated by adding nitrogen fertilizer
      to increase and sugar to decrease available nitrogen. Plant density was
      manipulated by pulling by hand 25 or 50% of Borrichia stems on each plot. Because
      our main focal herbivore was a gall making fly, Asphondylia borrichiae, which
      attacks only the apical meristems of plants, manipulating plant nitrogen levels
      was a convenient and reliable way to change plant quality without impacting
      quantity because fertilizer and sugar altered plant nitrogen content but not
      plant density. Our other focal herbivore was a sap-sucker, Pissonotus
      quadripustulatus, which taps the main veins of leaves. Parasitism of both
      herbivores was reduced via yellow sticky traps that caught hymenopteran
      parasitoids. Plant quality significantly affected the per stem density of both
      herbivores, with fertilization increasing, and sugar decreasing the densities of
      the two species but stem density manipulations had no significant effects.
      Parasitoid removal significantly increased the densities of both herbivores. Top
      down manipulations resulted in a trophic cascade, as the density of Borrichia
      stems decreased significantly on parasitoid removal plots. This is because
      reduced parasitism increases gall density and galls can kill plant stems. In this
      system, plant quality and natural enemies impact per stem herbivore population
      densities but plant density does not.

PMID- 15517408
TI  - Spatial avoidance of littoral and pelagic invertebrate predators by Daphnia.
AB  - Studies on spatial avoidance behaviour of predators by prey often ignored the
      fact that prey typically face multiple predators which themselves interact and
      show a spatial pattern in abundance and predation rates (PRs). In a series of
      laboratory experiments, we investigated predation risk (PRI) and horizontal
      migration of the cladoceran Daphnia magna between open water and vegetation in
      response to two important invertebrate predators with a contrasting spatial
      distribution: pelagic Choaborus and vegetation-associated Ischnura. As expected,
      PRI by Chaoborus was higher in open water due to higher numbers and higher PRs of
      Chaoborus, while for Ischnura, PRI was highest in the vegetation due to higher
      densities, despite lower PRs of Ischnura. In accordance with this, Daphnia moved
      into the vegetation in the presence of the pelagic Chaoborus alone. In the
      presence of Ischnura alone, however, Daphnia showed no response. We hypothesize
      this may be the result of a constitutive behaviour of Daphnia to avoid pelagic
      fish, which impedes a response to the open water. In the combined predator
      treatment, Daphnia migrated to the open water zone. The increased risk of
      predation in the vegetation, due to a facilitating effect of Chaoborus on
      Ischnura PRs is believed to have caused this migration of the Daphnia. This
      response of Daphnia declined through time and Daphnia moved toward the
      vegetation. A decline in the activity of the Ischnura larvae through time may
      have switched the risk balance in favour of the vegetation environment.

PMID- 15517409
TI  - Detecting predation and scavenging by DNA gut-content analysis: a case study
      using a soil insect predator-prey system.
AB  - White grubs (larvae of Coleoptera: Scarabaeidae) are abundant in below-ground
      systems and can cause considerable damage to a wide variety of crops by feeding
      on roots. White grub populations may be controlled by natural enemies, but the
      predator guild of the European species is barely known. Trophic interactions
      within soil food webs are difficult to study with conventional methods.
      Therefore, a polymerase chain reaction (PCR)-based approach was developed to
      investigate, for the first time, a soil insect predator-prey system. Can,
      however, highly sensitive detection methods identify carrion prey in predators,
      as has been shown for fresh prey? Fresh Melolontha melolontha (L.) larvae and 1-
      to 9-day-old carcasses were presented to Poecilus versicolor Sturm larvae.
      Mitochondrial cytochrome oxidase subunit I fragments of the prey, 175, 327 and
      387 bp long, were detectable in 50% of the predators 32 h after feeding.
      Detectability decreased to 18% when a 585 bp sequence was amplified. Meal size
      and digestion capacity of individual predators had no influence on prey
      detection. Although prey consumption was negatively correlated with cadaver age,
      carrion prey could be detected by PCR as efficiently as fresh prey irrespective
      of carrion age. This is the first proof that PCR-based techniques are highly
      efficient and sensitive, both in fresh and carrion prey detection. Thus, if
      active predation has to be distinguished from scavenging, then additional
      approaches are needed to interpret the picture of prey choice derived by highly
      sensitive detection methods.

PMID- 15517410
TI  - The persistence of ripe fleshy fruits in the presence and absence of frugivores.
AB  - A trade-off between antimicrobial defences and palatability to dispersers may
      place limits on fruit persistence in nature. The retention times of ripe fruits
      on 34 wild plant species under natural conditions (unbagged persistence) and when
      fruits had been bagged with nylon mesh to exclude frugivores (bagged persistence)
      were compared in Hong Kong, China (22 degrees N). Bagged persistence is a measure
      of the effectiveness of fruit defence while unbagged persistence is an inverse
      measure of attractiveness to vertebrate frugivores. Bagged fruits persisted
      significantly longer than unbagged fruits in 30 species, with half the species
      tested persisting for more than 2 months. There was a significant positive
      relationship between the median persistence times of bagged and unbagged fruits,
      suggesting that species with a high resistance to microbial infection are also
      less attractive to frugivores. Both bagged and unbagged fruits persisted
      significantly longer at lower temperatures. There was a significant positive
      relationship between bagged persistence time and fibre content of the fruit pulp,
      but no significant relationships between unbagged persistence and the six fruit
      traits tested (diameter, pulp as a percentage of fruit fresh weight, and lipid,
      total soluble carbohydrate, nitrogen and fibre as percentages of pulp dry
      weight). Mechanical damage significantly decreased the bagged persistence time
      for half of the species. Although some fruits decayed or dried up while attached
      to the plant, fruits of 53% of the species remained visually attractive until
      they fell off.

PMID- 15517412
TI  - Cyclosporin A does not affect platelets in children with idiopathic nephrotic
      syndrome.
AB  - The immunosuppressive agents administered to maintain the remission of idiopathic
      nephrotic syndrome (INS) may have a deleterious effect on several cell types. The
      aim of this study was to analyze platelet activation and reactivity in children
      with INS treated with cyclosporin A (CyA). The study groups comprised 16 children
      with remission of INS induced by CyA and 16 children with glucocorticosteroid
      induced remission 8 weeks from the onset of INS relapse. Fifteen healthy children
      served as controls. Surface expression of CD61, CD62P, and CD42b on resting and
      thrombin-stimulated platelets was analyzed with flow cytometry. No differences
      between groups were found in CD61, CD62P, and CD42b surface expression, but
      markers of the coagulation cascade and fibrinolysis or endothelial injury (F1+2
      prothrombin fragments, tissue plasminogen activator inhibitor 1) were elevated in
      patients treated with CyA compared with children on steroids and healthy
      controls. No correlations between markers of platelet function and CyA
      concentration were found. We postulate that CyA administration in nephrotic
      patients causes an activation of thrombinogenesis but does not influence platelet
      activation and reactivity in INS.

PMID- 15517413
TI  - Changes of blood pressure and left ventricular mass in pediatric renal
      transplantation.
AB  - Cardiovascular events are among the most frequent causes for long-term morbidity
      and mortality in children after renal transplantation. The aim of this study was
      to analyze the effects of post-transplant changes in arterial hypertension, as
      assessed by 24-h ambulatory blood pressure measurement (ABPM), on myocardial
      architecture, as assessed by echocardiography. In a retrospective chart review
      analysis, 39 children were identified in whom 24-h ABPM and echocardiography had
      been assessed within a 3-month interval after a mean of 4 years post
      transplantation; 20 repeated pairs of measurements after a mean of 2 years of
      follow-up were available to analyze the longitudinal effects of post-transplant
      changes of blood pressure control on left ventricular mass index (LVMI). Arterial
      hypertension (59%) and left ventricular hypertrophy (50%) were highly prevalent
      in children after renal transplantation. Renal allograft function and number of
      antihypertensive medications, but not ABPM variables, were correlated with LVMI
      at the initial observation. However, at repeat assessment, a significant
      correlation between ABPM and LVMI was found. In the longitudinal assessment, left
      ventricular remodeling was dependent on change of dosage of cyclosporine and
      interval changes of blood pressure levels. Hence, control of blood pressure
      correlates with changes of LVMI in children with renal allografts. These results
      clearly underline the importance of blood pressure control for the maintenance of
      the myocardial architecture.

PMID- 15517414
TI  - Calcimimetics--fooling the calcium receptor.
AB  - The cloning and characterization of a calcium-sensing receptor from bovine
      parathyroid cells has opened up the possibility of modulating the activity of
      this receptor protein by organic small molecules, either increasing the
      sensitivity for calcium (calcimimetics) or decreasing the sensitivity
      (calciolytics), thus suppressing or stimulating parathyroid hormone (PTH)
      secretion and synthesis, respectively. In primary and secondary
      hyperparathyroidism, calcimimetics have proven to effectively lower the PTH
      concentration with minimal side effects. In secondary hyperparathyroidism, a
      specific advantage is the concomitant lowering of serum calcium and phosphate
      concentrations.

PMID- 15517415
TI  - Bone mineral density and bone turnover markers in children with chronic renal
      failure.
AB  - Bone mineral density (BMD) at lumbar spine (L2-L4) was measured by dual-energy X
      ray absorptiometry (DEXA) in 21 children with predialysis chronic renal failure
      (CRF) and 44 children with end-stage renal failure (ESRF) on regular
      hemodialysis. BMD results were expressed as Z-scores. Osteopenia was documented
      in 13 predialysis patients (61.9%) and 26 patients (59.1%) with ESRF. No
      significant correlation was observed between Z-scores and the duration of CRF or
      estimated creatinine clearance. In osteopenic children there was a negative
      correlation between Z-scores and serum phosphorus (r=-0.61, P=0.004), intact
      parathyroid hormone (iPTH) (r=-0.47, P=0.03), and bone-specific alkaline
      phosphatase (r=-0.52, P=0.02) and a positive correlation with total calcium
      (r=0.41, P=0.07) and 25-hydroxycholecalciferol (r=0.53, P=0.02). Osteopenic
      children who had iPTH values > or = 200 pg/ml were more osteopenic than those who
      had lower iPTH levels (P=0.006). In conclusion, osteopenia, assessed by DEXA, is
      frequent in children with CRF. It occurs early irrespective of the duration or
      the severity of CRF. In children with ESRF the degree of osteopenia is correlated
      with laboratory markers of renal osteodystrophy and patients with biochemical
      findings of secondary hyperparathyroidism are more osteopenic than the others.

PMID- 15517416
TI  - Abnormal left ventricular mass and aortic distensibility in pediatric dialysis
      patients.
AB  - There is ample evidence that the same pathophysiological processes that affect
      cardiovascular function in adults with end-stage renal disease (ESRD) also
      operate in children with ESRD. In adults undergoing hemodialysis (HD), a good
      correlation has been established between left ventricular mass (LVM) and aortic
      distensibility (AD) as markers of cardiovascular disease progression; however,
      this correlation has not been established in children. Therefore, in this
      retrospective study we investigated some aspects of cardiovascular damage (i.e.,
      LVM, LVMI, and AD) in children with ESRD undergoing HD (n=9) or peritoneal
      dialysis (PD, n=9), and analyzed the relationship between AD, LVM, LVMI, pre
      dialysis, post-dialysis blood pressure (BP), and demographic factors in children
      and adolescents with ESRD. Both LVM and AD were significantly greater in the
      dialysis population than in a control population derived from our institutional
      files (P=0.015, P=0.001). LVM and LVMI in children undergoing HD (92.9+/-83.7 g,
      80.1+/-31.1 g/cm) were not statistically different from the values in children on
      PD (130.0+/-89.2 g, 89.6+/-35.9 g/cm), (P=0.3, P=0.5). AD in children on HD
      (2.2+/-0.55 cm2* dynes(-1*(10-6)) was significantly lower than in children on PD
      (2.7+/-0.54 cm2* dynes(-1*(10-6)), (P=0.01). The findings in this study confirm
      earlier studies that demonstrated that LVMI is greater in children on dialysis.
      This study also demonstrates that abnormal vascular stiffness, as defined by AD,
      is present in these children. The degree of vascular stiffness in children
      receiving HD is greater than in children receiving PD. However, further study is
      needed to address how control of BP, uremia, and other factors may affect these
      abnormalities in children with ESRD.

PMID- 15517417
TI  - Effect of fluid overload and dose of replacement fluid on survival in
      hemofiltration.
AB  - Continuous renal replacement therapy (CRRT) is used to treat renal failure in
      children. Despite widespread use of the technique, little research has evaluated
      how variations in dose of replacement fluid or degree of fluid overload at
      initiation relate to outcomes. We conducted a retrospective review of patients
      treated with convective CRRT at our institution, using a multivariable Cox
      regression model. Children with high fluid overload (>10%) at CRRT initiation
      were at 3.02 times greater risk of mortality than those with low or no fluid
      overload [95% confidence interval (CI) 1.50-6.10, P=0.002]. The hazard ratio for
      death in children treated with high-dose convective clearance was not
      statistically significant. Our data support previous findings that volume
      overload in excess of 10% is strongly correlated with poor outcome. We favor
      early institution of CRRT, before excessive fluid overload occurs. In contrast to
      findings in adults, we find no advantage to higher rates of convective clearance.
      Given the risks and increased complexity associated with high-volume
      hemofiltration, we recommend further study prior to widespread adoption of high
      level convection in children treated with continuous veno-venous hemofiltration.

PMID- 15517418
TI  - Hemoperfusion in a child with amitriptyline intoxication.
AB  - Tricyclic antidepressant overdose is one of the most common causes of serious
      drug poisoning in children and adults. We report a 17-month-old girl with severe
      amitriptyline intoxication. She was admitted to hospital because of lethargy and
      seizures. It was estimated that she took approximately 75 mg/kg of amitriptyline
      2 h before admission. On examination she was comatose, had ventricular
      tachycardia and multifocal clonic seizures. Intravenous fluid, per oral activated
      charcoal, diazepam, lidocaine, and sodium bicarbonate infusion were given.
      However, there was no response to this therapy, and the patient remained in a
      deep coma with cardiac arrhythmias and seizures. Hemoperfusion (HP) was performed
      for 2 h. During this procedure, cardioversion was used six times due to
      ventricular fibrillation. She had a very good clinical response to HP and no
      complication was observed. We suggest that HP may be an effective treatment in
      children with severe amitriptyline intoxication.

PMID- 15517419
TI  - Long-term effects of levamisole treatment in childhood nephrotic syndrome.
AB  - The effects of levamisole treatment on long-term outcome were evaluated in a
      retrospective study of frequently-relapsing (FRNS, n=15), steroid-dependent
      (SDNS, n=13), and steroid-resistant (SRNS, n=6) nephrotic syndrome in 34 children
      (21 boys, 13 girls, mean age 5.0+/-3.4 years) during a 60-month follow-up period.
      The definition of frequent relapses was > or = 4 relapses per year. The current
      relapse was treated with prednisolone 60 mg/m2 per day for 4 weeks, then with 40
      mg/m2 every other day for 4 weeks, after which the dose was tapered by 10 mg
      weekly. From the beginning of the 5th week, levamisole was introduced at a dose
      of 2 mg/kg per day. The duration of levamisole treatment was 17+/-7 months.
      Before starting levamisole treatment the mean level of proteinuria was 2.17+/
      1.34 g/day and the relapse rate was 4.41/year. By the end of levamisole therapy,
      proteinuria had fallen to 0.142+/-0.211 g/day and the relapse rate to 0.41/year.
      No relapse occurred in 23 of the 34 patients during levamisole treatment. In the
      24-month follow-up period after the discontinuation of levamisole, 28 children
      remained in total remission, while 6 had relapses. The cumulative steroid dose
      before levamisole therapy was 7,564.4+/-3,497.1 mg/year and following the
      introduction of levamisole 1,472.9+/-1,729.9 mg/year (P<0.0001). We observed
      reversible neutropenia in 5 patients, but no other side effects were seen. Our
      findings suggest that in FRNS and SDNS levamisole significantly reduces both the
      relapse rate and the cumulative steroid dose; therefore, it could be recommended
      for these patients. In SRNS patients it has also some benefit because proteinuria
      and the cumulative steroid dose could be reduced significantly.

PMID- 15517420
TI  - Formation of structures resembling ericoid mycorrhizas by the root endophytic
      fungus Heteroconium chaetospira within roots of Rhododendron obtusum var.
      kaempferi.
AB  - A resynthesis study was conducted to clarify the relationship between the root
      endophyte, Heteroconium chaetospira and the ericaceous plant, Rhododendron
      obtusum var. kaempferi. The host plant roots were recovered 2 months after
      inoculation, and the infection process and colonization pattern of the fungus
      were observed under a microscope. The hyphae of H. chaetospira developed
      structures resembling ericoid mycorrhizas, such as hyphal coils within the host
      epidermal cells. These structures were morphologically the same as previously
      reported ericoid mycorrhizal structures. The frequencies of hyphal coils within
      the epidermal cells of host roots ranged from 13 to 20%. H. chaetospira did not
      promote or reduce host plant growth. This is the first reported study that H.
      chaetospira is able to form structures resembling mycorrhizas within the roots of
      ericaceous plants.

PMID- 15517421
TI  - Seasonal variation of arbuscular mycorrhizal fungi in temperate grasslands along
      a wide hydrologic gradient.
AB  - We studied seasonal variation in population attributes of arbuscular mycorrhizal
      (AM) fungi over 2 years in four sites of temperate grasslands of the Argentinean
      Flooding Pampas. The sites represent a wide range of soil conditions, hydrologic
      gradients, and floristic composition. Lotus glaber, a perennial herbaceous legume
      naturalised in the Flooding Pampas, was dominant at the four plant community
      sites. Its roots were highly colonised by AM fungi. Temporal variations in spore
      density, spore type, AM root colonisation, floristic composition and soil
      chemical characteristics occurred in each site and were different among sites.
      The duration of flooding had no effect on spore density but depressed AM root
      colonisation. Eleven different types of spores were recognized and four were
      identified. Two species dominated at the four sites: Glomus fasciculatum and
      Glomus intraradices. Spore density was highest in summer (dry season) and lowest
      in winter (wet season) with intermediate values in autumn and spring.
      Colonisation of L. glaber roots was highest in summer or spring and lowest in
      winter or autumn. The relative density of G. fasciculatum and G. intraradices
      versus Glomus sp. and Acaulospora sp. had distinctive seasonal peaks. These
      seasonal peaks occurred at all four sites, suggesting differences among AM fungus
      species with respect to the seasonality of sporulation. Spore density and AM root
      colonisation when measured at any one time were poorly related to each other.
      However, spore density was significantly correlated with root colonisation 3
      months before, suggesting that high colonisation in one season precedes high
      sporulation in the next season.

PMID- 15517422
TI  - Morphological-anatomical characterization and molecular identification of
      Tomentella stuposa ectomycorrhizae and related anatomotypes.
AB  - Species in the genus Tomentella (Thelephoraceae) belong to the most frequent and
      widespread ectomycorrhizal (EM) fungi found in temperate and boreal forests.
      Although several unidentified tomentelloid morphotypes have been presented as
      common members of EM communities in coniferous and broad-leaved forests, few
      tomentelloid EM have been identified and described in detail. In this study, ten
      tomentelloid EM isolates collected from Populus alba, Quercus cerris and Picea
      abies stands in Hungary and Germany are characterized and documented by
      morphological-anatomical methods using light microscopy. The investigated
      ectomycorrhizae belong to the same brown-black tomentelloid morphotype but form
      two different anatomotype groups (At I and At II). Molecular taxonomical
      identification was accomplished using phylogenetic analysis (neighbor joining
      method) of 49 Tomentella nrDNA-ITS nucleotide sequences including the 10 new and
      39 GenBank sequences. The EM isolates clustered into two adjoining clades
      identical with the two anatomotypes. At II clustered with Tomentella stuposa
      while At I could not be identified to species. Based on the morphological
      similarity and the low genetic difference it must be a closely related taxon. A
      comparison of the recently known tomentelloid EM to T. stuposa is presented.
      Ecological questions involving abundance and host relationships are discussed.

PMID- 15517423
TI  - Response to cadmium of Daucus carota hairy roots dual cultures with Glomus
      intraradices or Gigaspora margarita.
AB  - Ri T-DNA-transformed carrot roots were cultivated in two experiments either non
      inoculated or inoculated with the arbuscular mycorrhizal (AM) fungi Glomus
      intraradices or Gigaspora margarita. The influence of two concentrations of
      cadmium (Cd) in the medium (2 mg l(-1), 4 mg l(-1)) on both root and mycelium
      growth was tested. Both parameters were estimated at 10-day intervals for 70 or
      100 days for G. intraradices and Gi. margarita, respectively. In the first
      experiment, G. intraradices showed a rapid spread of extraradical mycelium (ERM)
      and reached average densities per treatment of about 90 cm cm(-2) agar medium
      after 70 days. At the higher Cd level, the growth of ERM was delayed in
      comparison to the treatment without Cd addition. Root growth was inhibited by
      both Cd levels; the inhibition was, however, significantly lower in the
      treatments inoculated with G. intraradices compared to the non-inoculated
      control. In the second experiment, the ERM of Gi. margarita started to grow after
      a period of 50 days and reached average densities per treatment of only up to 27
      cm cm(-2) by the end of the cultivation. The growth of Gi. margarita mycelium was
      not inhibited by Cd. No differences in root growth were observed between the Gi.
      margarita inoculated and non-inoculated treatments. The inhibitory effect of Cd
      on root growth differed between the non-inoculated treatments in both
      experiments. The study has shown that the AM fungus Glomus intraradices can
      alleviate Cd-induced growth inhibition to carrot hairy roots. The potential and
      limits of the monoxenic system in studying the interaction between AM fungi and
      heavy metals are discussed.

PMID- 15517424
TI  - A non-randomized clinical control trial of Harrison mirror image methods for
      correcting trunk list (lateral translations of the thoracic cage) in patients
      with chronic low back pain.
AB  - Spinal trunk list is a common occurrence in clinical practice, but few
      conservative methods of spinal rehabilitation have been reported. This study is a
      non-randomized clinical control trial of 63 consecutive retrospective subjects
      undergoing spinal rehabilitation and 23 prospective volunteer controls. All
      subjects presented with lateral thoracic-cage-translation posture (trunk list)
      and chronic low back pain. Initial and follow-up numerical pain rating scales
      (NRS) and AP lumbar radiographs were obtained after a mean of 11.5 weeks of care
      (average of 36 visits) for the treatment group and after a mean of 37.5 weeks for
      the control group. The radiographs were digitized and analyzed for a horizontal
      displacement of T12 from the second sacral tubercle, verticality of the lumbar
      spine at the sacral base, and any dextro/levo angle at mid-lumbar spine.
      Treatment subjects received the Harrison mirror image postural correction
      methods, which included an opposite trunk-list exercise and a new method of
      opposite trunk-list traction. Control subjects did not receive spinal
      rehabilitation therapy, but rather self-managed their back pain. For the
      treatment group, there were statistically significant improvements (approximately
      50%) in all radiographic measurements and a decrease in pain intensity (NRS: 3.0
      to 0.8). For the control group, no significant radiographic and NRS differences
      were found, except in trunk-list displacement of T12 to S1, worsened by 2.4 mm.
      Mirror image (opposite posture) postural corrective exercises and a new method of
      trunk-list traction resulted in 50% reduction in trunk list and were associated
      with nearly resolved pain intensity in this patient population. The findings
      warrant further study in the conservative treatment of chronic low back pain and
      spinal disorders.

PMID- 15517425
TI  - Early changes in pulmonary function following thoracotomy for scoliosis
      correction: the effect of size of incision.

PMID- 15517427
TI  - Prostaglandin-mediated control of rat brain kynurenic acid synthesis--opposite
      actions by COX-1 and COX-2 isoforms.
AB  - Kynurenic acid (KYNA), an endogenous glutamate-receptor antagonist preferentially
      blocking NMDA-receptors, has analgesic properties and has also been implicated in
      the pathophysiology of schizophrenia. Recently, the non-steroid anti-inflammatory
      drug (NSAID) diclofenac was found to increase rat brain KYNA. Here, we analyze
      whether cyclooxygenase (COX)-1 or COX-2 modulate the levels of rat brain KYNA.
      The non-selective COX-inhibitor diclofenac (50 mg/kg, i.p.) or indomethacin (50
      mg/kg, i.p.), a non-selective inhibitor with a preferential selectivity for COX
      1, produced an elevation in brain KYNA. In contrast, the COX-2 selective
      inhibitors parecoxib (25 mg/kg, i.p.) or meloxicam (5 mg/kg, i.p.) decreased
      brain KYNA. Both elevation and lowering of brain KYNA by indomethacin or
      parecoxib, respectively, were prevented by the prostaglandin E1/E2 agonist
      misoprostol (1 mg/kg, s.c.). It is proposed that increased brain KYNA formation
      induced by NSAIDs displaying an inhibitory action on COX-1 contribute to their
      analgesic efficacy as well as to their psychiatric side effects.

PMID- 15517428
TI  - Reduced prefrontal response control in patients with schizophrenias: a subgroup
      analysis.
AB  - We investigated the function of the anterior cingulate cortex (ACC) with the
      continuous performance test (CPT) in patients with chronic schizophrenias. We had
      previously shown that the NoGo anteriorisation (NGA), which consists of a more
      anterior center of gravity (centroid) of the event-related potentials during the
      inhibition of a prepared motor response, correlates with physiological activation
      of the ACC in healthy probands. However, in patients with schizophrenias, the
      event-related potentials are located more anteriorly in the Go condition and more
      posteriorly in the NoGo condition, which leads to a decreased NGA reflecting
      reduced activation of the ACC. We now extend our observations to a larger number
      of patients with different subgroups of chronic schizophrenias according to
      Leonhard's classification system. While the schizophrenic patients as a group
      showed only a trend towards a decreased NGA, there was a significant reduction of
      the NGA in patients with systematic schizophrenias but not in those with
      unsystematic schizophrenias. Our results show that a subclassification of
      "schizophrenic" patients is useful to detect differences between subgroups, which
      may reflect differences in pathophysiology.

PMID- 15517429
TI  - Changes in negative symptoms and EEG in schizophrenic patients after repetitive
      transcranial magnetic stimulation (rTMS): an open-label pilot study.
AB  - The effects of repetitive transcranial magnetic stimulation (rTMS) on
      schizophrenic negative symptoms (NS) and EEG topography were investigated in this
      pilot study. 10 patients with predominant NS were treated with 10 Hz rTMS over
      the left dorsolateral prefrontal cortex for 5 days. For NS ratings, the Scale for
      the Assessment of Negative Symptoms (SANS) was used. Both ratings and EEG
      recordings were obtained pre- and post-rTMS. Electrical activity changes were
      computed by Low Resolution Brain Electromagnetic Tomography. SANS showed an
      improvement after rTMS, from 49.0 (SD: 10.7) to 44.7 (SD: 11.8) (means). EEG
      frequency bands were changed fronto-temporally (right) and were mainly decreases
      in delta- and beta- and increases in alpha1-activity, as well as decreases in
      beta-activity in the temporal and parieto-occipital regions (left). Although we
      are aware of the limitations of this study, we assume a slight improvement in NS.
      The EEG findings refer to a possible neurophysiologic correlate of their
      improvement after rTMS.

PMID- 15517430
TI  - 7-nitroindazole, nNOS inhibitor, attenuates amphetamine-induced amino acid
      release and nitric oxide generation but not lipid peroxidation in the rat brain.
AB  - The aim of the present study was to elucidate whether amphetamine modulates the
      output of the neurotransmitters glutamate, aspartate, GABA and acetylcholine
      (ACh) in nucleus accumbens (NAc) as well as the formation of lipid peroxidation
      (LPO) and nitric oxide (NO). D,L-amphetamine (AMPH, 5 mg/kg, i.p., 4 times every
      2 h) was injected into anaesthetized rats and the release of neurotransmitters in
      the NAc, tissue content of NO and LPO products were determined. While AMPH
      increased the release of aspartate, GABA and ACh in the NAc, the glutamate
      release was not affected. Levels of NO and LPO products were elevated in striatum
      and cortex. Pretreatment with the neuronal NO synthase inhibitor 7-nitroindazole
      (50 mg/kg, i.p.) was highly effective in abating the rise of the neurotransmitter
      release and NO generation but failed to influence the intensity of LPO elicited
      by the AMPH administration. These findings suggest that activation of NO
      synthesis is a potent factor in the AMPH-induced neurotransmitter release and
      that activation of NO synthesis and LPO by AMPH are not parallel processes.

PMID- 15517431
TI  - The dopamine D4 receptor gene exon III polymorphism is associated with novelty
      seeking in 15-year-old males from a high-risk community sample.
AB  - In recent years, studies focussing on a possible association between the dopamine
      D4 receptor (DRD4) gene exon III polymorphism and the personality trait of
      novelty seeking (NS) have yielded inconsistent results. The present study sought
      to examine the association of the DRD4-7r allele with NS in a sample of 303 15
      year-old adolescents (144 males, 159 females) using data from a high-risk
      community sample. The Junior Temperament and Character Inventory--JTCI/12-18 was
      administered to assess dimensions of adolescent temperament. Males in the DRD4-7r
      allele group scored significantly higher on the NS (p=.002) and the harm
      avoidance (p=.045) scales than males without this allele. In females no
      association with temperament was observed. This association could not be
      explained by the presence of either an attention-deficit/hyperactivity disorder
      (ADHD) or a DRD4 by ADHD interaction.

PMID- 15517432
TI  - Post-translational modifications of tau protein in Alzheimer's disease.
AB  - Microtubule-associated protein tau undergoes several post-translational
      modifications and aggregates into paired helical filaments (PHFs) in Alzheimer's
      disease (AD) and other tauopathies. These modifications of tau include
      hyperphosphorylation, glycosylation, ubiquitination, glycation, polyamination,
      nitration, and proteolysis. Hyperphosphorylation and glycosylation are crucial to
      the molecular pathogenesis of neurofibrillary degeneration of AD. The others
      appear to represent failed mechanisms for neurons to remove damaged, misfolded,
      and aggregated proteins. This review summarizes the abnormal post-translational
      modifications of tau and discusses the pathophysiological relevance of
      hyperphosphorylation and glycosylation of tau. Total tau and phosphorylated tau
      levels in cerebrospinal fluid as a diagnostic biomarkers are also reviewed.
      Analyses of the current advances in tau modifications suggest that intervention
      addressing these abnormalities may offer promising therapeutic opportunities to
      prevent and treat neurofibrillary degeneration of AD and other tauopathies.

PMID- 15517433
TI  - High dose vitamin E therapy in amyotrophic lateral sclerosis as add-on therapy to
      riluzole: results of a placebo-controlled double-blind study.
AB  - Increasing evidence has suggested that oxidative stress may be involved in the
      pathogenesis of amyotrophic lateral sclerosis (ALS). The antioxidant vitamin E
      (alpha-tocopherol) has been shown to slow down the onset and progression of the
      paralysis in transgenic mice expressing a mutation in the superoxide dismutase
      gene found in certain forms of familial ALS. The current study, a double blind,
      placebo-controlled, randomised, stratified, parallel-group clinical trial, was
      designed to determine whether vitamin E (5000 mg per day) may be efficacious in
      slowing down disease progression when added to riluzole. METHODS: 160 patients in
      6 German centres with either probable or definite ALS (according to the El
      Escorial Criteria) and a disease duration of less than 5 years, treated with
      riluzole, were included in this study and were randomly assigned to receive
      either alpha-tocopherol (5000 mg per day) or placebo for 18 months. The Primary
      outcome measure was survival, calculating time to death, tracheostomy or
      permanent assisted ventilation, according to the WFN-Criteria of clinical trials.
      Secondary outcome measures were the rate of deterioration of function assessed by
      the modified Norris limb and bulbar scales, manual muscle testing (BMRC),
      spasticity scale, ventilatory function and the Sickness Impact Profile (SIP
      ALS/19). Patients were assessed at entry and every 4 months thereafter during the
      study period until month 16 and at a final visit at month 18. Vitamin E samples
      were taken for compliance check and Quality Control of the trial. For Safety, a
      physical examination was performed at baseline and then every visit until the
      treatment discontinuation at month 18. Height and weight were recorded at
      baseline and weight alone at the follow-up visits. A neurological examination as
      well as vital signs (heart rate and blood pressure), an ECG and VEP's were
      recorded at each visit. Furthermore, spontaneously reported adverse experiences
      and serious adverse events were documented and standard laboratory tests
      including liver function tests performed. For Statistical Analysis, the
      population to be considered for the primary outcome measure was an "intent-to
      treat" (ITT) population which included all randomised patients who had received
      at least one treatment dose (n = 160 patients). For the secondary outcome
      measures, a two way analysis of variance was performed on a patient population
      that included all randomised patients who had at least one assessment after
      inclusion. RESULTS: Concerning the primary endpoint, no significant difference
      between placebo and treatment group could be detected either with the stratified
      Logrank or the Wilcoxon test. The functional assessments showed a marginal trend
      in favour of vitamin E, without reaching significance. CONCLUSION: Neither the
      primary nor the secondary outcome measures could determine whether a megadose of
      vitamin E is efficacious in slowing disease progression in ALS as an add-on
      therapy to riluzol. Larger or longer studies might be needed. However,
      administration of this megadose does not seem to have any significant side
      effects in this patient population.

PMID- 15517434
TI  - Computerized movement analysis and beta-CIT-SPECT in patients with restless legs
      syndrome.
AB  - Considering the positive effect of dopaminergic treatment on Restless Legs
      Syndrome (RLS), it has been suggested that the cause of RLS may be linked to
      central dopaminergic dysfunction. As problems of alternating movements can result
      from a failure in the dopaminergic system, we used a movement analysis system to
      analyse this and in-parallel, performed [123I]beta-CIT-SPECT to investigate signs
      of dopaminergic dysfunction in patients with RLS. In 10 patients with idiopathic
      RLS, we conducted a three-dimensional computerized ultrasound-based movement
      analysis before a single dose of levodopa (L-dopa) was given and 90 minutes after
      the L-dopa challenge. In 6 of the 10 RLS patients, the striatal dopamine
      transporter system was studied with [123I]beta-CIT-SPECT. We did not observe any
      significant change in the movement pattern with the computerized movement
      analysis and no significant effect of L-dopa on the movement. We did not detect
      any significant differences between patients and normal controls regarding beta
      CIT-signals in putamen or caudate nucleus, respectively. There was, however, a
      slight but significant change regarding the relative [123I]beta-CIT-SPECT binding
      in the putamen vs. the caudate nucleus. We conclude that the methods used could
      not detect any definite signs of changed central dopaminergic function in
      patients with RLS.

PMID- 15517435
TI  - Olfactory function in patients with idiopathic Parkinson's disease: effects of
      deep brain stimulation in the subthalamic nucleus.
AB  - Decrease of olfactory function in patients with Parkinson's disease (PD) is a
      well-investigated fact. The present study aimed to investigate olfaction in PD
      patients with a specific focus on the effects of deep brain stimulation in the
      subthalamic nucleus. Eleven patients (age 42-67 years) participated in this
      study. Using the "Sniffin' Sticks", olfactory function was assessed based on
      butanol odor thresholds and the patients' ability to discriminate odors. Measures
      were taken with the stimulator being switched ON and OFF, respectively. While
      deep brain stimulation had no effect on odor thresholds, in hyposmic PD patients
      odor discrimination was found to be significantly higher during the ON period.
      This may indicate that deep brain stimulation has a positive effect on the
      cognitive processing of olfactory information in PD patients.

PMID- 15517437
TI  - Direct monitoring of the electron pool effect of cytochrome c3 by highly
      sensitive EQCM measurements.
AB  - Cytochrome c(3) from Desulfovibrio vulgaris has four hemes per molecule, and a
      redox change at the hemes alters the conformation of the protein, leading to a
      redox-dependent change in the interaction of cytochrome c(3) with redox partners
      (an electron acceptor or an electron donor). The redox-dependent change in this
      interaction was directly monitored by the high-performance electrochemical quartz
      crystal microbalance (EQCM) technique that has been improved to give high
      sensitivity in solution. In this method, cytochrome c(3) molecules in solution
      associate electrostatically with a viologen-immobilized quartz crystal electrode
      as a monolayer, and redox of the associating cytochrome c(3) is controlled by the
      immobilized viologen. This technique makes it possible to measure the access of
      cytochrome c(3) to the electrode or repulsion from the electrode, and hence
      interconversion between an electrostatic complex and an electron transfer complex
      on the cytochrome c(3) and the viologen as a mass change accompanying a potential
      sweep is monitored. In addition, simultaneous measurement of a mass change and a
      potential step reveals that the cytochrome c(3) stores electrons when the four
      hemes are reduced (an electron pool effect), that is, the oxidized cytochrome
      c(3) facilitates acceptance of electrons from the immobilized viologen molecule,
      but the reduced cytochrome c(3) donates the accepted electrons to the viologen
      with difficulty.

PMID- 15517440
TI  - [Limitations of blood supply to the skin flap in face lift surgery].
AB  - BACKGROUND: Besides nerve injuries or hematomas, one of the main risks of face
      lift surgery is the development of skin necrosis. We therefore investigated which
      arteries contribute to the blood supply of the face lift skin flap and how
      extensively mobilization can be performed before arterial cutaneous circulation
      is endangered. MATERIAL AND METHOD: In six cadavers, selective dye injections
      into the branches of the carotid external artery were performed to determine the
      location of their vascular territories in relation to the face lift region. In
      another 12 cadavers, face lift flaps were raised with different extension of the
      undermined skin area before dye injections were performed. RESULTS: It was shown
      that the facial artery provides blood supply to the area of the face lift flap by
      perforating vessels in the paranasal, perioral and submental regions and the
      transverse facial artery by a perforating vessel below the malar bone prominence.
      Although the perforating vessel of the transverse facial artery was transected by
      standard mobilization, the face lift flaps were sufficiently perfused via the
      paranasal and perioral perforating vessels of the facial artery alone.
      CONCLUSION: We conclude that undermining of the face lift flap should not exceed
      the nasolabial fold to preserve the perforating vessels of the facial artery in
      the centrofacial region.

PMID- 15517438
TI  - Large cooperativity in the removal of iron from transferrin at physiological
      temperature and chloride ion concentration.
AB  - Iron removal from serum transferrin by various chelators has been studied by gel
      electrophoresis, which allows direct quantitation of all four forms of
      transferrin (diferric, C-monoferric, N-monoferric, and apotransferrin). Large
      cooperativity between the two lobes of serum transferrin is found for iron
      removal by several different chelators near physiological conditions (pH 7.4, 37
      degrees C, 150 mM NaCl, 20 mM NaHCO(3)). This cooperativity is manifested in a
      dramatic decrease in the rate of iron removal from the N-monoferric transferrin
      as compared with iron removal from the other forms of ferric transferrin.
      Cooperativity is diminished as the pH is decreased; it is also very sensitive to
      changes in chloride ion concentration, with a maximum cooperativity at 150 mM
      NaCl. A mechanism is proposed that requires closure of the C-lobe before iron
      removal from the N-lobe can be effected; the "open" conformation of the C-lobe
      blocks a kinetically significant anion-binding site of the N-lobe, preventing its
      opening. Physiological implications of this cooperativity are discussed.

PMID- 15517441
TI  - [Botulinum toxin for treatment of gustatory sweating. A prospective randomized
      study].
AB  - BACKGROUND: Botulinum toxin A has meanwhile become a proven method for treatment
      of gustatory sweating (focal hyperhidrosis, Frey's syndrome). Clear-cut
      recommendations regarding dosage of botulinum toxin A in Frey's syndrome are
      currently not available. The aim of this prospective randomized study therefore
      was to investigate botulinum toxin A with respect to its efficacy in Frey's
      syndrome, the ideal dose yielding maximal duration of the effect, and patient
      contentedness as well as unwanted side effects in patients of the Clinic of OMF
      Surgery at the Ruhr-University of Bochum. PATIENTS AND METHOD: Twenty patients
      suffering from severe Frey's syndrome as a result of operations of the parotid
      gland were examined with the starch iodine test according to Minor. The gustatory
      skin areas were re-examined after intracutaneous injection of botulinum toxin A
      for up to 1 year. The patients ( n=20) were randomly assigned to two different
      treatment groups (group I: 2 MU/cm(2), n=10; group II: 3 MU/cm(2), n=10).
      RESULTS: Mean sweating skin areas in the two treatment groups ranged between 39+/
      9 and 32+/-12 cm(2), respectively. A single injection of 3 MU botulinum toxin A
      resulted in a nearly complete blockade of gustatory sweating for the observation
      period of 1 year. In the group treated with 2 MU botulinum toxin A, 44% of the
      total gustatory skin areas were still sweating, thus necessitating a second
      injection of botulinum toxin A in these patients. CONCLUSION: Intracutaneous
      injection of botulinum toxin A represents a highly effective and minimally
      invasive procedure for the treatment of Frey's syndrome. This study shows for the
      first time that a dosage of 3 MU/cm(2) of botulinum toxin A achieves a complete
      and reliable blockade of gustatory sweating lasting for at least 12 months. This
      dose may therefore be recommended for treatment of this syndrome.

PMID- 15517442
TI  - Endoscopic totally extraperitoneal repair of incarcerated inguinal hernia.
AB  - BACKGROUND: Incarcerated inguinal hernias have been considered a relative
      contraindication for endoscopic surgery, as its efficacy and safety is as yet
      unproven. With more experience and improved techniques, management of
      incarcerated hernias by the endoscopic approach has become possible with
      decreased patient discomfort and acceptable results. AIM AND OBJECTIVE: To
      analyze the feasibility and effectiveness of Endoscopic Totally Extraperitoneal
      repair in incarcerated inguinal hernias. METHODS: We retrospectively analyzed 34
      patients-admitted under a single surgical unit with chronically incarcerated
      inguinal hernias-who underwent an elective endoscopic totally extraperitoneal
      repair. The 6-year period studied was from May 1997 to May 2003. Demographic
      characteristics, operative details (including modifications in technique and use
      of drains) and postoperative outcome including analgesic requirements, hospital
      stay, complications, and time taken to resume normal activity, were evaluated. A
      comparison was made with the results of 286 endoscopic primary, non-incarcerated,
      unilateral endoscopic totally extraperitoneal hernia repairs done during the same
      period. RESULTS: With the help of modified techniques for reduction of the
      hernial sac, all the patients underwent a successful TEP repair. There were no
      conversions. The mean operating time was 84.4 min compared to 57 min in the non
      incarcerated group. Three-fourths of the patients could be discharged within 24
      h. Analgesic requirement was for an average of 5.5 days (vs 4.2 days in the non
      incarcerated group). Time taken to resume normal activity was 7.5 days (vs 5.6
      days in the non-incarcerated group). Two recurrences occurred. Follow-up period
      ranged from 13 months to 84 months. CONCLUSIONS: With the help of modifications
      in operating technique, Endoscopic Totally Extraperitoneal repair is feasible and
      effective in patients with incarcerated inguinal hernias and encompasses the
      advantages of endoscopic procedures.

PMID- 15517443
TI  - British contributions to modern herniology of the groin.
AB  - Traditional disdain for groin repair stifled recognition of British innovations.
      Some, relating to modern herniology, are remembered herein. Morton (1841) and
      Mackay (1889) showed the epigastric artery piercing Cooper's transversalis fascia
      (1807). Bilaminarity (Cooper, 1807) was confirmed in 1992 (Read). Thomson's
      iliopubic tract (1838) became part of Nyhus' repair (1960) [derived from
      McEvedy's repair (1950)] and laparoscopy (Ger, 1982). Retzius' space (Edinburgh,
      1858) with Lister's antisepsis (1865) enabled preperitoneal herniorrhaphy
      (Annandale, 1876). He participated (1873) in intraperitoneal release of
      incarceration and reducible protrusions (Tait 1883). Cheyne's pectineus muscle
      plug (1893) preceded Kelly's marble prosthesis for femoral herniation (1898).
      Cheatle (1920) introduced posterior preperitoneal repair-ignored, rediscovered
      (Henry, 1936), and adopted (1952) at the Mayo clinic. Calne (1967) pioneered
      retrorectus Mersilene and was followed by Stoppa (1969) and Wantz (1989). Brandon
      (1945) blamed failure of modified Bassini's herniorrhaphies on closure at the
      intermediate inguinal ring instead of the internal. A similar mechanism may
      explain interstitial recurrence (Gilbert, 2003) after Amid-Lichtenstein repair.
      Lytle (1896-1986) described a muscle shutter at the internal ring, course of
      genitofemoral nerve, and orifice of femoral canal. Russell's congenital saccular
      theory (1906) was questioned by Keith (1924). Acquired connective-tissue
      pathology was later shown to play a systematic role in adult groin herniation
      (Read, 1970), confirmed by Jackson and colleagues (1996) and others.

PMID- 15517444
TI  - Anthropometric characteristics of the pubic arch and proper function of the
      defense mechanisms against hernia formation.
AB  - In 33 inguinal regions, we determined the anthropometric characteristics of the
      pubic arch and the anatomic structures of the suprainguinal space and assessed
      whether there is a relationship between anatomic features and function of the
      defense mechanisms. There was a low position of the pubic arch (pubic tubercle
      and interspinal line distance >75 mm) in 23 cases. The low-pubic-arch group
      showed a significantly longer inguinal ligament and a greater angle made by the
      superior border of the suprainguinal space and the inguinal ligament at its
      medial insertion. The position of the pubic arch correlated significantly with
      the diameter of the internal ring, the length of the inguinal ligament, and the
      angle made by the superior border of the suprainguinal space and the medial
      insertion of the inguinal ligament. A low pubic arch would represent an
      unfavorable condition for an adequate function of the anatomic defense mechanism
      against hernia.

PMID- 15517445
TI  - Early onset autosomal dominant spastic paraplegia caused by novel mutations in
      SPG3A.
AB  - Hereditary spastic paraplegia (HSP) is a group of neurodegenerative disorders
      mainly characterized by progressive spasticity of the lower limbs. The major
      features of HSP are a marked phenotypic variability both among and within
      families and an extended genetic heterogeneity. More than 20 HSP loci and 10
      spastic paraplegia genes (SPG) have been identified to date, including the genes
      responsible for the two most frequent forms of autosomal dominant spastic
      paraplegia (AD-HSP), encoding spastin (SPG4) and atlastin (SPG3A), respectively.
      To date, only eight mutations have been described in the atlastin gene, which was
      reported to account for about 10% of all AD-HSP families. We investigated 15
      German and French AD-HSP families, including the 3 large pedigrees that allowed
      the mapping and subsequent refinement of the SPG3A locus. Three novel mutations
      were found in exons 4, 9, and 12 of the atlastin gene and the common R239C
      mutation located in exon 7 was confirmed in a 7th family of European origin.
      Overall, the comparison of the clinical data for all SPG3A-HSP families reported
      to date failed to reveal any genotype/phenotype correlation as demonstrated for
      other forms of AD-HSP. However, it confirmed the early onset of this form of HSP,
      which was observed in almost all affected individuals with a mutation in the
      atlastin gene.

PMID- 15517446
TI  - Variable atrioventricular block in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE), a connective tissue disease characterized by
      the production of auto-antibodies and immune complexes, can affect all organs
      including the heart. The involvement of the conduction system in SLE has been
      less commonly described. We report a case of an asymptomatic 45-year-old woman
      with SLE referred to the emergency department (ED) for thrombocytopenia, and was
      found to have alternating first- and second-degree atrioventricular block (AVB)
      during routine electrocardiographic screening for hospital admission. Serial
      electrocardiograms (ECG) done in the ED when compared to those recorded 24 h
      prior revealed progression from mild first-degree AVB (PR interval = 216 ms) to
      significant first-degree AVB (PR interval = 510 ms), followed by second-degree
      AVB (Mobitz type I-Wenckebach phenomenon). The conduction abnormalities recorded
      over a 28-h period resolved with corticosteroid treatment. Review of the
      literature on the disruption of the cardiac conduction system in SLE is
      discussed.

PMID- 15517447
TI  - Transverse myelitis in a patient with Behcet's disease: favorable outcome with a
      combination of interferon-alpha.
AB  - We report here on a 24-year-old patient with Behcet's disease who had been
      diagnosed with acute transverse myelitis. He was successfully treated with a
      combination regimen of a steroids, cyclophosphamide, and interferon-alpha. The
      treatment strategy with specific emphasis on interferon-alpha is discussed in the
      light of the pertinent literature.

PMID- 15517448
TI  - Kikuchi-Fujimoto's disease associated with systemic lupus erythematosus: case
      report and review of the literature.
AB  - Kikuchi-Fujimoto's disease (KFD) or histiocytic necrotising lymphadenitis is a
      benign and self-limited disease, of unknown aetiology, which affects mainly young
      women. It presents with localised lymphadenopathy, predominantly in the cervical
      region, accompanied by fever and leukopenia in up to 50% of the cases. KFD has
      been rarely described in association with systemic lupus erythematosus (SLE), and
      its diagnosis can precede, postdate or coincide with the diagnosis of SLE. We
      present a patient with the diagnosis of SLE characterised by arthritis,
      leukopenia, malar rash, photosensitivity and positive ANA, besides cervical
      lymphadenopathy whose biopsy was compatible with KFD, which improved after using
      prednisone. Although the presence of lymphadenopathy is not uncommon in SLE
      patients, particularly in the phases of disease activity, the concomitance with
      KFD has rarely been reported in the literature. Its recognition is necessary
      because one can avoid laborious investigation for infectious and
      lymphoproliferative diseases.

PMID- 15517451
TI  - Application of lower fluence rate for less microvasculature damage and greater
      cell-killing during photodynamic therapy.
AB  - During the process of photodynamic therapy (PDT), problems arise such as stasis
      or occlusion of microvasculature, tumor oxygen depletion, and photosensitizer
      bleaching. This study shows that the first problem could be reduced by using a
      lower fluence rate light source in PDT. Microvasculature damage was studied
      experimentally in hematoporphyrin derivative-mediated PDT against light fluence
      rate, and, to some extent, less microvasculature damage was induced under 75
      mW/cm(2) illumination than under 150 mW/cm(2). Histology of vessels at the end of
      PDT showed that vessel damage could be observed in both groups, indicating that
      the microvasculature would eventually be damaged as long as the administration of
      light fluence was sufficient and regardless of the illuminating fluence rates.
      Thus microvasculature damage induced by low fluence rate illumination could also
      be effective in tumor control after PDT. The cell-killing experiment was
      performed in vitro and designed so that cell-killing rate was influenced only by
      light characteristics. The higher cell-killing rate caused by 75 mW/cm(2)
      illumination indicated that lower fluence rate light could enhance the light
      absorbency or decrease the bleaching of photosensitizer.

PMID- 15517452
TI  - Enteroenteric intussusception secondary to a lipoma: CT diagnosis.
AB  - We present a young woman who was hospitalized for abdominal pain and vomiting.
      Abdominal CT revealed diagnostic features of ileoileal intussusception with a
      central hypodense lesion of fat density suggestive of a lipoma as the lead point.
      This diagnosis was confirmed at surgery, where a small bowel resection was
      performed and a benign lipoma of the ileum was found.

PMID- 15517453
TI  - Multidetector CT in shoulder fractures.
AB  - The aim of this study was to assess the multi-detector computed tomography (MDCT)
      findings in acute shoulder traumas compared to radiographic findings in patients
      referred to a level one trauma center. Two hundred and ten patients (128 male, 82
      female, age 16-95 years, mean age 51.7 years) underwent shoulder MDCT due to
      acute trauma. Three main mechanisms of injury were established: falling (113
      patients, 54%), traffic accidents (36 patients, 17%) and falling from a height
      (12 patients, 6%). Based on MDCT, a total of 311 fractures--152 in the scapula
      and 159 in the proximal humerus--occurred in 191 (91%) of the 210 patients. The
      two most common occult fractures were lesser tubercle and coracoid process
      fractures. In 20 (63%) of the patients with a comminuted fracture of proximal
      humerus the exact number of fracture fragments was underestimated in radiographs.
      MDCT with multiplanar reconstructions (MPR) is a recommended complementary
      examination in patients with complex proximal humerus fractures where the extent
      of the fractures and the position or origin of dislocated fragments is not clear
      on radiography. This may increase the accuracy of the fracture classification and
      reveal occult fractures in other parts of the shoulder.

PMID- 15517454
TI  - Multidetector row CT diagnosis of aortocaval fistula complicating aortic
      aneurysm: a case report.
AB  - Aortocaval fistula is a rare complication of abdominal aortic aneurysm involving
      less than 1% of all abdominal aortic aneurysms and causing severe hemodynamic
      derangements from a large left-to-right shunt; early diagnosis and repair results
      in improved morbidity and lower mortality but the diagnosis is difficult. We
      report a case of prompt diagnosis obtained with thoracoabdominal aortic
      multidetector row angio-CT as the first imaging procedure and allowing immediate
      surgical repair. Our report emphasizes the crucial role played by multidetector
      row CT as the first procedure in thoracoabdominal vascular emergencies.

PMID- 15517455
TI  - 3D CT evaluation of retained foreign bodies.
AB  - Retained foreign bodies in the abdomen and pelvis are an uncommon occurrence
      after surgical operations but have serious medicolegal implications. The
      radiologist plays an important role in suggesting the diagnosis of a retained
      foreign body. This article reviews the use of three-dimensional CT as a problem
      solving tool in the identification, localization, and presurgical planning of
      retained surgical foreign bodies.

PMID- 15517456
TI  - Heterogeneous nature of the dynamics and glass transition in thin polymer films.
AB  - Recent experiments have demonstrated that the dynamics in liquids close to and
      below the glass transition temperature is strongly heterogeneous, on the scale of
      a few nanometers. We use here a model proposed recently for explaining these
      features, and show that the heterogeneous nature of the dynamics has important
      consequences when considering the dynamics of thin films. We show how the
      dominant relaxation time in a thin film is changed as compared to the bulk, as a
      function of the thickness, the interaction energy with the substrate, and the
      temperature. The corresponding time scales cover the so-called VFT (or WLF)
      regime and vary between 10(-8) s to 10(4) s typically. In the absence of
      interaction, our model allows for interpreting suspended films experiments, in
      the case of small polymers for which the data do not depend on the polymer
      weight. The interaction leads to an increase of T(g) for an interaction per
      monomer of the order of the thermal energy T. This increase saturates at the
      value corresponding to strongly interacting films for adsorption energies
      slightly larger and still of order T. In particular, we predict that the T(g)
      shift can be non-monotonous as a function of the film thickness, in the case of
      intermediate interaction strength.

PMID- 15517457
TI  - Monte Carlo simulation of particle aggregation and gelation: II. Pair correlation
      function and structure factor.
AB  - Diffusion-limited cluster aggregation and gelation are studied using lattice and
      off-lattice Monte Carlo simulations. The pair correlation function g(r) and the
      structure factor S(q) of the particle gels were investigated as a function of the
      volume fraction (05-49%) and time. At volume fractions below 5%, the gel
      structure is fractal on small length scales with d(f) = 1.8. g(r) shows a weak
      minimum at the correlation length (xi), before reaching the average concentration
      at large length scales. The cut-off function of g(r) varies during the
      aggregation process, but at a given t/t(g), where t(g) is the gel time, it is a
      universal function of r/xi. At high volume fractions, the structure is dominated
      by excluded-volume interactions, while at low volume fractions, it is determined
      by the connectivity.

PMID- 15517458
TI  - Monte Carlo simulation of particle aggregation and gelation: I. Growth, structure
      and size distribution of the clusters.
AB  - Lattice and off-lattice Monte Carlo simulations of diffusion-limited cluster
      aggregation and gelation were done over a broad range of concentrations. The
      large-scale structure and the size distribution of the clusters are characterized
      by a crossover at a characteristic size (m(c)). For m < m(c), they are the same
      as obtained in a dilute DLCA process and for m >> m(c) they are the same as
      obtained in a static percolation process. m(c) is determined by the overlap of
      the clusters and decreases with increasing particle concentration. The growth
      rate of large clusters is a universal function of time reduced by the gel time.
      The large-scale structural and temporal properties are the same for lattice and
      off-lattice simulations. The average degree of connectivity per particle in the
      gels formed in off-lattice simulations is independent of the concentration, but
      its distribution depends on the concentration.

PMID- 15517459
TI  - Force response of a viscous liquid in a probe-tack geometry: fingering versus
      cavitation.
AB  - We perform traction experiments on viscous liquids highly confined between
      parallel plates, a geometry known as the probe-tack test in the adhesion
      community. Direct observation during the experiment coupled to force measurement
      shows the existence of several mechanisms for releasing the stress: while
      fingering is favored for low traction velocities, low confinement and low
      viscosity, nucleation of bubbles occurs in the opposite conditions. It is
      possible to quantitatively predict the transition between the two regimes and, in
      many respects, describe the shape of the force response. Using a model for purely
      viscous fluids, we also present a phase diagram for the different force peak
      regimes that remarkably accounts for the data. Our results show that conspicuous
      features of the traction curve commonly thought to be characteristic of soft
      viscoelastic solids like adhesives are already encountered in liquid materials.

PMID- 15517460
TI  - Membrane tensiometer for heavy giant vesicles.
AB  - One key parameter of giant-vesicles adhesion is their membrane tension, sigma. A
      theoretically simple but delicate way to impose (and measure) it is to use
      micropipette manipulation techniques. But usually, the vesicles are free and
      their tension is unknown, until an adhesion patch grows. Sigma can be deduced
      from the detailed profile of the membrane close to the substrate, but this method
      is limited to very low tensions. We present here a rather simple way to estimate
      the membrane tension of heavy vesicles, which sediment close to a surface, by
      observing by RIM the size of the flat region of the vesicle. As an application,
      we follow the slow flattening of vesicles, when the surrounding sugar solution is
      evaporating, and their light-induced tensioning.

PMID- 15517461
TI  - Bayesian regression models for cost-effectiveness analysis.
AB  - Recent studies have shown how cost-effectiveness analysis can be undertaken in a
      regression framework. This contribution explores the use of practical regression
      models for estimating cost-effectiveness from a Bayesian perspective. Two
      different Bayesian models are described. The first considers the outcome measure
      to be a quantitative variable. In the second model the individual outcome measure
      is a binary variable with value 1 if any objective has been achieved. We describe
      the implementation of the model using data from a trial that compares two highly
      active antiretroviral therapies in HIV asymptomatic patients. Data on direct cost
      and data effectiveness (percentage of patients with undetectable viral load and
      quality of life) were recorded. If we consider the quality of life as an
      effectiveness measure, the new treatment is preferred for a willingness to pay
      more than Euro 142.3 for an increase in the quality of life. For illustrative
      purposes, if we compare the results with an analogous model that does not include
      covariates, the critical value becomes Euro 247.4. For the binary measure of
      effectiveness the control treatment dominates the new treatment.

PMID- 15517462
TI  - The enteric toxins of Clostridium perfringens.
AB  - The Gram-positive pathogen Clostridium perfringens is a major cause of human and
      veterinary enteric disease largely because this bacterium can produce several
      toxins when present inside the gastrointestinal tract. The enteric toxins of C.
      perfringens share two common features: (1) they are all single polypeptides of
      modest (approximately 25-35 kDa) size, although lacking in sequence homology, and
      (2) they generally act by forming pores or channels in plasma membranes of host
      cells. These enteric toxins include C. perfringens enterotoxin (CPE), which is
      responsible for the symptoms of a common human food poisoning and acts by forming
      pores after interacting with intestinal tight junction proteins. Two other C.
      perfringens enteric toxins, epsilon-toxin (a bioterrorism select agent) and beta
      toxin, cause veterinary enterotoxemias when absorbed from the intestines; beta-
      and epsilon-toxins then apparently act by forming oligomeric pores in intestinal
      or extra-intestinal target tissues. The action of a newly discovered C.
      perfringens enteric toxin, beta2 toxin, has not yet been defined but precedent
      suggests it might also be a pore-former. Experience with other clostridial toxins
      certainly warrants continued research on these C. perfringens enteric toxins to
      develop their potential as therapeutic agents and tools for cellular biology.

PMID- 15517464
TI  - Histological analysis in shoot organogenesis from hypocotyl explants of Kandelia
      candel (Rhizophoraceae).
AB  - In vitro culture of hypocotyl explants from Kandelia candel, a common mangrove
      species, on hormone-free Murashige and Skoog (MS) medium resulted in shoot
      formation. Since the hypocotyls showed good potential for in vitro shoot
      multiplication, the process of bud primordium formation was analyzed from a
      histological viewpoint. A wound periderm first appeared at the top, exposed cut
      surface of the explants. The wound-induced meristem continued to divide giving
      rise to suberized cells oriented towards the cut surface. After formation of the
      suberized cell layers, the meristem and its inner derivatives differentiated into
      multilayered, uniformly packed parenchyma cells. Bud primordia differentiated
      from the dense cytoplasmic cells of the wound-induced meristem just beneath the
      suberized layer near the severed vascular bundles. Each explant produced several
      visible shoot buds. Furthermore, histological sections revealed that additional
      bud primordia were present within the explant just underneath the suberized cells
      and that these bud primordia appeared to be arrested in their development. The
      fact that additional bud primordia were present within the explant suggests that
      further manipulation of the explant is helpful to maximize the potential of this
      system.

PMID- 15517465
TI  - Saponin-induced release of single cells from filaments and rhizoid
      differentiation in Spirogyra.
AB  - Some species of Spirogyra living in streams can anchor to the substratum by
      differentiating a rhizoid from a terminal cell of a filament. Rhizoid
      differentiation occurs in the light but not in the dark. When a filament of
      Spirogyra sp. competent for rhizoid differentiation was incubated in a medium
      containing 0.1% saponin, terminal cells were released one by one, forming single
      cells. Single cells effectively differentiated to be rhizoids when saponin in the
      incubation medium was removed. The single-cell system developed in the present
      study seems suitable for analysis of gene expression during rhizoid
      differentiation of Spirogyra.

PMID- 15517467
TI  - Rapid identification of microbial VOCs from tobacco molds using closed-loop
      stripping and gas chromatography/time-of-flight mass spectrometry.
AB  - Several microbial volatile organic compounds (MVOCs) that can serve as potential
      chemical markers for microbial contamination in tobacco have been identified.
      Four different fungal species, Aspergillus niger (AN), A. ornatus (AO),
      Pencillium chrysogenum (PC) and Rhizopus stolonifer (RS), commonly reported in
      moldy tobacco were cultured and screened for MVOCs. Because the MVOCs emitted by
      a microbial species are substrate specific, the fungal strains were separately
      grown on potato dextrose agar (PDA) and tobacco products. MVOCs from the mold
      cultures grown on PDA and tobacco products were extracted using closed-loop
      stripping analysis (CLSA) and identified by gas chromatography/time-of-flight
      mass spectrometry (GC/TOF-MS). Some of the prominent tobacco mold markers
      identified by this method include: 1-octen-3-ol; 2-octen-1-ol; 2-methyl-1
      butanol; 3-methyl-1-butanol; 1-octene and 2-pentanone. In particular, 1-octen-3
      ol was detected in all the mold cultures and moldy tobacco samples analyzed.
      Olfactory evaluation of 1-octen-3-ol indicated a characteristic musty odor and
      the odor threshold was determined to be approximately 200 ng/ml. The limits of
      detection for 1-octen-3-ol using GC/TOF-MS and GC/mass selective detector (MSD)
      in the full-scan mode and selected ion monitoring (SIM) mode were investigated.
      The CLSA-GC/TOF-MS demonstrates a fast, sensitive and semi-quantitative
      analytical technique for screening tobacco materials for the presence of mold via
      chemical markers of microbial contamination.

PMID- 15517468
TI  - Rat cerebral ischemia induced with photochemical occlusion of proximal middle
      cerebral artery: a stroke model for MR imaging research.
AB  - A stroke model in rats with photochemically induced thrombosis (PIT) of proximal
      cerebral middle artery (MCA) is introduced for magnetic resonance imaging (MRI)
      study. Thirty-seven rats subjected to surgical and optical procedures for
      inducing the PIT models were scanned using a 1.5-T scanner with T1-weighted
      imaging (T1WI), T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and
      contrast-enhanced perfusion-weighted imaging (PWI) at 1 h and 24 h after MCA
      occlusion. The penumbra evolution and PWI-derived parameters including relative
      cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) were
      monitored; and the relative lesion size (RLS) was compared with the final RLS on
      the gold standard triphenyl tetrazolium chloride (TTC) staining at 24 h. The
      results showed that the focal cerebral ischemic lesions were detectable in all
      rats with different MR approaches. The lesion on PWI at 1 h and on all MR images
      at 24 h was matched well with that seen on TTC staining; the peri-infarct area
      decreased from 6.2 +/- 7.2% of the brain volume at 1 h to 0.3 +/- 5.6% at 24 h.
      Compared to that in the contralateral hemisphere, rCBV in ischemic region was
      52.6 +/- 21.4 and 40.0 +/- 15.8% (p > 0.05), and rCBF was 64.6 +/- 11.2 and 47.3
      +/- 11.1% (p < 0.05) at 1 h and 24 h respectively. The present PIT model in rats
      has been successfully adopted for MRI research, which might be feasible for
      certain stroke studies and should be beneficial for the evaluation on effects of
      potential diagnostic and therapeutic approaches.

PMID- 15517469
TI  - Multi-spin-echo J-resolved spectroscopic imaging without water suppression:
      application to a rat glioma at 7 T.
AB  - Two-dimensional J-resolved spectroscopy may be used to separate resonances which
      overlap in 1D NMR spectra. Coupled with spectroscopic imaging (SI), it would give
      unequivocal information on the distribution of such resonances. Multi-echo
      acquisition decreases the minimum experimental time of such 4D experiments. The
      water peak may be used for phase and chemical-shift reference. This study aimed
      to demonstrate the feasibility of J-resolved SI based on a multi-echo sequence
      and without water suppression, and its ability to separate the peaks for lactate
      and mobile lipid in a rat glioma. Experiments were performed on rat brain,
      without water suppression, at 7 T. The water signal was used for correcting the
      phase of the echoes. A FOCSY-like acquisition was used to collect the first part
      of the echoes at short echo times. Two different data processing methods were
      tested to overcome the problem of contaminations of metabolite signals by the
      intense water signal. Maps of N-acetylaspartate, choline, creatine, lactate and
      mobile lipids were obtained in vivo on a rat glioma in 70 min. The in-plane
      resolution was 2 mm2. The 2D spatially resolved, 2D J-resolved spectra enabled
      the separate mapping of lactate and mobile lipids.

PMID- 15517470
TI  - High-resolution MR imaging of the rat spinal cord in vivo in a wide-bore magnet
      at 17.6 Tesla.
AB  - The objective was to demonstrate the feasibility and to evaluate the performance
      of high-resolution in vivo magnetic resonance (MR) imaging of the rat spinal cord
      in a 17.6-T vertical wide-bore magnet. A probehead consisting of a surface coil
      that offers enlarged sample volume suitable for rats up to a weight of 220 g was
      designed. ECG triggered and respiratory-gated gradient echo experiments were
      performed on a Bruker Avance 750 wide-bore spectrometer for high-resolution
      imaging. With T*2 values between 5 and 20 ms, good image contrast could be
      obtained using short echo times, which also minimizes motion artifacts. Anatomy
      of healthy spinal cords and pathomorphological changes in traumatically injured
      rat spinal cord in vivo could be visualized with microscopic detail. It was
      demonstrated that imaging of the rat spinal cord in vivo using a vertical wide
      bore high-magnetic-field system is feasible. The potential to obtain high
      resolution images in short scan times renders high-field imaging a powerful
      diagnostic tool.

PMID- 15517471
TI  - High-resolution magnetic resonance imaging of iron-labeled myoblasts using a
      standard 1.5-T clinical scanner.
AB  - Myoblast transplantation is a promising means of restoring cardiac function in
      infarcted areas. For optimization of transplant protocols, tracking the location
      and fate of the injected cells is necessary. An attractive imaging modality for
      this is magnetic resonance imaging (MRI) as it is noninvasive and as iron-labeled
      myoblasts provide a signal attenuation in T2*-weighted protocols. The aim of this
      study was to develop an efficient iron-labeling protocol for myoblasts and to
      visualize single-labeled cells using a clinical 1.5-T scanner. Pig myoblasts were
      labeled with a superparamagnetic iron oxide (SPIO) agent using a liposome
      transfection agent. Labeling efficiency, toxicity, cell viability, and
      proliferative capacity were measured for 10 days. Magnetic resonance (MR) of
      myoblast cultures used a T2*-weighted three-dimensional protocol with a maximum
      in-plane resolution of 19.5 x 26.0 microm2 and 50 microm slices. Use of liposomes
      improved SPIO labeling efficiency. Labeling did not induce toxicity or affect
      cell viability or proliferation. The cell distribution as observed with light and
      fluorescence microscopy matched the signal voids observed in the MRI datasets.
      Liposomes promote fast, nontoxic and efficient SPIO labeling of myoblasts that
      can be tracked by MRI microscopy in clinical scanners using susceptibility
      weighted protocols.

PMID- 15517472
TI  - Spurious signals in DQF spectroscopy: two-shot stimulated echoes.
AB  - The most widely used technique for double-quantum filtered (DQF) single-voxel
      spectroscopy (SVS) is based on a symmetric PRESS sequence with two additional
      spatially unselective pi/2 pulses, one of which is usually frequency selective.
      The actual filtering, rejecting signals from all uncoupled resonances, can be
      done by suitable phase cycling of the rf pulses in successive shots, but in
      practice gradient filtering is always used. Under usual conditions the sequence
      repetition time is comparable to the spin-lattice relaxation time, and a
      stimulated echo is formed by five out of the ten rf pulses in two consecutive
      shots. This echo is not filtered out by the gradients, and additional phase
      cycling is needed to eliminate it. Its spatial origin is the full transverse
      slice selected by the last pulse of the PRESS sequence. The SVS shimming
      procedure may create an important field variation in this slice (outside the
      volume of interest VOI). Water singlet signals therefore appear in a band of
      frequencies other than 4.7 ppm, and remain unaffected by water suppression
      pulses. In practice phase-alternation schemes can reduce these spurious signals
      by several orders of magnitude, but even then they may mask the weak metabolite
      signals of interest. We describe a strategy to minimize these spurious signals
      and propose a 16-step phase cycling scheme that attenuates the stimulated echo in
      every two-step subcycle.

PMID- 15517473
TI  - Quantitative assessment of regional myocardial function in a rat model of
      myocardial infarction using tagged MRI.
AB  - We characterized global and regional left ventricular (LV) function during post
      myocardium infarction (MI) remodeling in rats, which has been incompletely
      described by previous MRI studies. To assess regional wall motion, four groups of
      infarcted animals corresponding to 1-2, 3-4, 6-8 and 9-12 weeks post-MI
      respectively were imaged using a fast gradient echo sequence with a 2D spatial
      modulation of magnetization (SPAMM) tagging preparation. An additional group was
      serially imaged (1-2 and 6-7 weeks post-MI) to assess the global function.
      Regional and global functional parameters of infarcted rats were compared to non
      infarcted normal rats. Compared to normal rats, a decrease in ejection fraction
      (70 +/-7 vs. 40 +/- 8%, p<0.05) was observed in rats with MI. Maximal and minimal
      principal stretches (lambda1, lambda2) and strains (E1, E2), principal angle
      (beta) and displacement varied regionally in normal rats but deviated
      significantly from the normal values in rats with MI particularly in the
      infarcted and adjacent zones. Not only was strain magnitude reduced segmentally
      post-MI, but strain direction became more circumferentially oriented,
      particularly in rats with larger infarctions. We report the first regional
      myocardial strain values in normal and infarcted rats. These results parallel
      findings in humans, and provide a unique tool to examine regional mechanical
      influences on the remodeling process.

PMID- 15517474
TI  - Quick intraoperative parathyroid hormone assay: surgical adjunct to allow limited
      parathyroidectomy, improve success rate, and predict outcome.
AB  - Intraoperative parathyroid hormone (PTH) assay (QPTH) has made possible less
      invasive operative approaches in the treatment of primary hyperparathyroidism
      with stated advantages. When compared to the traditional bilateral neck
      exploration (BNE), only the targeted, hypersecreting gland is excised, leaving in
      situ non-visualized but normally functioning parathyroids. The QPTH-guided
      limited parathyroidectomy (LPX) must be able to identify multiglandular disease
      (MGD), predict a successful outcome, and have a low recurrence rate. In our
      series, 421 patients who underwent LPX were compared to 340 undergoing BNE; all
      operative failures and patients followed for 6 months or longer were included.
      Operative failure occurred if serum calcium and PTH levels were elevated within 6
      months of parathyroidectomy. Multiglandular disease was defined in the LPX group
      as more than one gland excision guided by QPTH or operative failure after removal
      of a single abnormal gland; in the BNE group it was defined as excision of more
      than one enlarged gland. Recurrence was defined as elevated calcium and PTH after
      6 months of eucalcemia. Operative failure and MGD rates were compared using chi
      squared analysis. The method of Kaplan-Meier and the log-rank test were used to
      compare recurrence rates. Operative success was seen in 97% of LPX patients and
      in 94% of the BNE group ( p = 0.02). Multiglandular disease was identified in 3%
      of LPX patients and 10% of BNE patients ( p < 0.001). There was no statistical
      difference in the overall recurrence rates ( p = 0.23). The QPTH-guided
      parathyroidectomy identifies MGD and allows an improved success rate with the
      same low recurrence rate when compared to the results of BNE.

PMID- 15517476
TI  - Partial versus total adrenalectomy by the posterior retroperitoneoscopic
      approach: early and long-term results of 325 consecutive procedures in primary
      adrenal neoplasias.
AB  - The retroperitoneoscopic approach is a standardized operative procedure for
      primary adrenal gland tumors. It allows direct access with a detailed view of the
      adrenal gland. Thereby, a clear differentiation between normal and neoplastic
      adrenal tissue is often possible, which permits a planned partial resection of
      the gland in selected cases. Between July 1994 and November 2003 325 posterior
      retroperitoneoscopic adrenalectomies were performed for primary benign adrenal
      gland tumors (106 Conn's adenomas, 83 pheochromocytomas, 76 Cushing's adenomas,
      60 nonfunctioning tumors; size: 2.8 +/- 1.5 cm; site: 160 right, 165 left) in 318
      patients (122 M, 196 F, age: 49.0 +/- 14.3 years). In 96 patients 100 tumors were
      removed by partial adrenalectomy (30 Conn's adenomas, 33 pheochromocytomas, 20
      Cushing's adenomas, 17 nonfunctioning tumors; site: 61 right, 59 left)
      maintaining tumor-free parts of the adrenal gland. Of this group, 15 patients
      suffered from bilateral adrenal neoplastic diseases. During the same period, 225
      total adrenalectomies (76 Conn's adenomas, 50 pheochromocytomas, 56 Cushing's
      adenomas, 34 nonfunctioning tumors; site: 109 right, 116 left) were performed in
      224 patients. There was no mortality. Major complications were seen in 1.8%,
      minor complications in 14.5%. Three conversions were necessary to an open or a
      laparoscopic approach (2 patients and 1 patient, respectively). There are no
      differences between the two groups (total versus partial adrenalectomy) with
      regard to tumor size (2.8 +/- 1.6 cm versus 2.8 +/- 1.5 cm), operating time (80
      +/- 44 minutes versus 79 +/- 42 minutes), and blood loss (33 +/- 71 ml versus 29
      +/- 31 ml). In all patients with partial adrenalectomy, biochemical healing was
      proven. Fourteen of 15 patients with bilateral diseases had preservation of
      adrenocortical function. After a mean follow up of 51 months (range: 7-120
      months) local recurrence or relapse of the initial diseases was noticed in 6
      patients after total adrenalectomy: in 4 patients with Conn's syndrome and
      bilateral hyperplasia, and in 2 patients with malignant pheochromocytoma and
      adrenocortical carcinoma, respectively. Our data demonstrate that partial
      adrenalectomy is a safe procedure not only perioperatively but also in the long
      term follow-up.

PMID- 15517477
TI  - Current concepts in functioning endocrine tumors of the pancreas.
AB  - Duodenal and pancreatic endocrine tumors are uncommon and their surgical
      treatment is often difficult. The management of these tumors has changed with
      recent advancements in tumor localization, intraoperative hormone measurements,
      standardized surgical techniques, and a better understanding of the genetic basis
      of multiple endocrine neoplasia syndrome. We present our experience with 191
      endocrine tumors and elaborate the contemporary management of functioning
      duodenopancreatic endocrine tumors.

PMID- 15517478
TI  - Value of the cervical compartments in the surgical treatment of papillary thyroid
      carcinoma.
AB  - In the treatment of papillary thyroid carcinoma (PTC), supplementary lymph node
      dissection (LND) is not well standardized. The purpose of this study was to
      evaluate the significance of the cervical compartments in the lymphatic spread of
      PTC and the impact of modified radical neck dissection (MRND) as an additional
      surgical procedure to thyroid resection. From 1999 to 2002, LND of the central
      compartment (compartment A) was performed in 39 patients. Among this group,
      additional MRND of the ipsilateral compartment (compartment B) and the
      contralateral compartment (compartment C) was performed in 29 and 15 patients
      respectively, who met the selection criteria. The mean number of nodes resected
      was 11 (5-22) in compartment A, 23 (8-37) in compartment B, and 22 (10-31) in
      compartment C. Histopathologic findings revealed node invasion of compartment A
      in 25 patients (64.1%), of A and B in 20 patients (51,2%) and of A, B, and C in
      13 patients (33.3%). From the 25 patients with metastases in compartment A, 80%
      (20 patients) already had metastases in compartment B and 52% (13 patients) had
      metastases in all three compartments. All patients free of metastasis (M0) in
      compartment A were also metastasis free in both lateral compartments.
      Postoperative whole-body scanning I(131) in M0 patients showed no uptake at all.
      Mapping of the cervical anatomy in compartments seems to be a useful taxonomy for
      clarifying the lymphatic spread of PTC. Patients having PTC without metastasis in
      compartment A are almost certainly disease free at the time of operation. Lymph
      node metastasis in the central compartment appears to be a valuable indicator of
      lymphatic invasion of the lateral compartment and a strong indication for
      performance of a unilateral or bilateral MRND to complete the surgical removal of
      tumor.

PMID- 15517479
TI  - Prospective evaluation of imaging procedures for the detection of
      pancreaticoduodenal endocrine tumors in patients with multiple endocrine
      neoplasia type 1.
AB  - Early identification of pancreaticoduodenal endocrine tumors (PETs) in multiple
      endocrine neoplasia type 1 (MEN-1) is mandatory, because these tumors represent
      the most common cause of death within the syndrome. The diagnostic value of
      imaging procedures has therefore been evaluated in a prospective observational
      study. Between December 1997 and June 2003 twenty-two MEN-1 patients with
      genetically confirmed disease were followed for PETs using a standardized
      screening program with serum hormone measurements, endoscopic ultrasonography
      (EUS), computed tomography (CT), and somatostatin-receptor scintigraphy (SRS).
      Results could be validated by surgery and histopathology in 13 patients during 18
      operations. In 12 asymptomatic patients with tumors measuring 10 mm or less, who
      have not yet undergone operation, PETs were detected by EUS in 12/12, by CT in
      1/12, and by SRS in 2/11 cases. In 13 patients who have undergone surgical
      exploration EUS, CT, and SRS were true positive in 12 of 16, 7 of 13, and 12 of
      17 cases, respectively, although the number of tumors detected by each imaging
      procedure alone was lower than the number detected intraoperatively and
      histopathologically in almost every case. A solitary liver metastasis in one
      patient and a nonfunctioning PET recurrence in another were identified only by
      SRS. Endoscopic ultrasonography is the most sensitive imaging procedure for the
      detection of small (< or = 10 mm) PETs in MEN-1, whereas SRS is the procedure of
      choice for the identification of metastases of MEN-1 PETs-i.e., for staging.
      Detection of PETs at an early stage by an aggressive screening program using EUS
      may lead to prompt surgical intervention and improved prognosis of MEN-1 PETs.

PMID- 15517480
TI  - Intraoperative parathyroid hormone monitoring.
AB  - The principles of minimally invasive parathyroidectomy include the successful
      preoperative localization of a solitary adenoma, a targeted operative approach
      that does not disturb the normal parathyroid glands, and intraoperative
      confirmation of excision of all hypersecreting parathyroid tissue. By providing
      real-time feedback to the surgical team, the rapid PTH assay allows surgeons to
      assess the completeness of parathyroid resection without visualizing all the
      parathyroid glands. Intraoperative PTH monitoring facilitates the use of local
      anesthesia, decreases the duration of surgery, and allows ambulatory surgery in
      most patients. This article reviews current recommendations and controversies
      surrounding the use of intraoperative PTH monitoring during parathyroidectomy.

PMID- 15517481
TI  - Timing and extent of surgery in patients with familial medullary thyroid
      carcinoma/multiple endocrine neoplasia 2A-related RET mutations not affecting
      codon 634.
AB  - In hereditary medullary thyroid carcinoma (MTC), recommendations regarding timing
      and extent of surgery are mainly based on the data of patients with the codon 634
      RET mutation, which is the most often affected codon. Little is known about
      whether these recommendations may also be applied to patients with less common
      RET mutations. We ascertained the data from 140 patients with FMTC/MEN2A-related
      RET mutation not affecting codon 634 who have been treated at three specialized
      centers. The several RET mutations found affected codons 611 (n = 17), 618 (n =
      22), 620 (n = 17), 768 (n = 9), 790 (n = 24), 791 (n = 21), 804 (n = 23), and 891
      (n = 7). For each codon, the age of the youngest patient with MTC only (41, 7,
      18, 29, 13, 47, 20, and 15 years, respectively), MTC with lymph node metastases
      (46, 24, 21, 34, 46, 47, 50, and 76 years, respectively), and MTC with distant
      metastases (52, 69, 43, 68, 57, - , - , and 75 years, respectively) was
      determined. All patients with lymph node metastases had elevated basal calcitonin
      levels. Based on these data, a more individual recommendation regarding timing
      and extent of surgery can be given. Because neither gender nor the type of
      nucleotide substitution for a specific codon appeared to have a significant
      influence on the age of onset, this recommendation should be based on the
      affected codon, the age of the patient, and the calcitonin level. Recurrent
      laryngeal nerve palsy (n = 6) and hypoparathyroidism (n = 3) were rather rare and
      were found only in patients older than 30 and 43 years, respectively, giving
      evidence that surgery in young patients can be performed safely.

PMID- 15517482
TI  - Technetium-99m 2-methoxyisobutyl isonitrile-scintigraphy: preoperative and
      intraoperative guidance for primary hyperparathyroidism.
AB  - As refinement of technetium-99m 2-methoxyisobutyl isonitrile-scintigraphy (MIBI)
      scintigraphy of parathyroid glands has continued since its initial use in 1989,
      the sensitivity, specificity, and overall accuracy of the technique have improved
      greatly, approaching 100% for larger, solitary adenomas. Preoperative use of
      sestamibi scintigraphy has become commonplace and allows surgeons the option of a
      minimally invasive, or focused approach for their patients with primary
      hyperparathyroidism. Intraoperative use of the gamma probe based on sestamibi
      localization has not caught on due to lesser accuracy, cumbersome gamma probes,
      small doses of radiation exposure for patients and staff, and the greater
      accuracy and current confidence in intraoperative parathormone (PTH) monitoring.
      However, with the potential for smaller and more accurate gamma probes that truly
      assist in localizing abnormal parathyroid glands, the potential for cost
      reduction by shortening operative times, avoiding expensive PTH assays, and
      eliminating the need for pathologic analysis, gamma scintigraphy may yet become a
      viable option for many parathyroid surgeons.

PMID- 15517483
TI  - Results of video-assisted parathyroidectomy: single institution's six-year
      experience.
AB  - Endoscopic surgery for primary hyperparathyroidism (PHPT) started in 1996 with a
      parathyroidectomy performed by Michel Gagner. The technique we propose and have
      been using for 6 years is based on a unique central access and external
      retraction. From February 1997 to October 2003, 370 of 520 patients affected with
      PHPT (71%) underwent minimally invasive video-assisted parathyroidectomy (MIVAP).
      There were 72 men and 298 women, with a mean age of 55.8 years. Twenty-four
      patients (6.5%) of the 370 in this series underwent MIVAP under loco-regional
      anesthesia, and the others had general anesthesia. Eleven patients were lost to
      follow-up. Surgical cure of PHPT was achieved in 353 patients (98,3%), as
      confirmed by a median follow-up of 35.1 months (range: 2-82 months). Video
      assisted exploration was successfully performed in 350 patients (94%). The mean
      operative time was 36.2 minutes. In 21 cases (5.6%) a concomitant procedure was
      performed: a thyroid lobectomy in 14 cases and a total thyroidectomy in 7 cases.
      Patients were generally discharged the day after surgery. Most of the patients
      (91%) were satisfied with the cosmetic result 6 or more months after the
      procedure. Complications developed in 14 cases: 10 cases (2.7%) of transient
      hypoparathyroidism 3 cases (0.8%) of definitive palsies of the recurrent nerve,
      and 1 case of postoperative bleeding (0.27%). After 6 years of experience, MIVAP
      appears to be as safe and curative as traditional surgery, with better cosmetic
      results and better postoperative outcome.

PMID- 15517484
TI  - Multiple endocrine neoplasia 2B syndrome due to codon 918 mutation: clinical
      manifestation and course in early and late onset disease.
AB  - More than 50% of patients with typical MEN-2B have a de novo M918T germline
      mutation of the RET protooncogene. However, even in typical MEN-2B,
      extrathyroidal manifestations of MEN-2B can be found to be differently expressed.
      We analyzed the clinical manifestation and course in 21 patients harboring a de
      novo RET M918T mutation. Mean age at MEN-2B diagnosis was 14.2 years (range: 1-31
      years). All patients had medullary thyroid carcinoma (MTC). At the time of
      syndrome diagnosis, oral manifestations (bumpy lips, ganglioneuroma), ocular
      manifestations (corneal fibers, conjunctivitis sicca), intestinal dysfunctions,
      musculoskeletal manifestations, and pheochromocytoma were found in 86%, 90%, 74%,
      79%, and 19% of the patients, respectively. At the time of follow-up examination,
      the symptoms were found at higher frequency. Severe intestinal manifestation was
      predominantly found in patients with prepubertal onset (< or = 12 years) of MTC
      (n = 4/10) compared with patients with late onset (> 12 years) of MTC (n = 0/11)
      (40% versus 0%; p = 0.019). Although biochemical cure was found only in four
      patients with early onset of MTC, the long-term prognosis for patients with early
      onset of MTC was poorer than for patients presenting with late onset of MTC (p =
      0.005). During mean follow-up of 55.8 months (range: 3-161 months), seven
      patients (33%) died from MTC. In conclusion, whereas most typical MEN-2B symptoms
      were found to be age-related, severe intestinal manifestation was found to be
      predominantly expressed in patients with early onset of MTC. Furthermore, in
      patients with early onset of MTC who could not be biochemically cured, the long
      term prognosis was found to be worse than that of non-cured patients with late
      onset of MTC, suggesting an additional pathological process in the younger
      subgroup reinforcing the very high transforming in vitro activity of the M918T
      RET mutation.

PMID- 15517485
TI  - Laparoscopic pancreatic surgery for islet cell tumors of the pancreas.
AB  - The experience with laparoscopic pancreatic surgery (LPS) in general, and
      pancreatic islet cell tumors (ICTs) in particular, is still limited. Because
      insulinoma is the most prevalent tumor and is mostly benign, single, and curable
      with surgical excision, it comprises most of the cases. Our experience with 17
      cases (10 insulinomas, 2 gastrinomas, 1 nesidioblastoma, 4 nonfunctioning tumors)
      and those recorded in the literature (93 cases) show that laparoscopic surgery
      for small, solitary benign islet cell tumors located in the body and tail is
      feasible and safe and can result in rapid postoperative recuperation and a
      complication rate comparable or lower than that achieved with open surgery. It
      duplicates the success rate seen with conventional surgery regarding
      intraoperative localization and cure of disease. The main morbidity continues to
      be the occurrence of a fistula (18%), most often after enucleation, but the
      clinical course is benign in most instances. Preoperative imaging studies are
      required for localization, and the combined use of biphasic helical computed
      tomography and endoscopic ultrasonography (US) seems to be cost-effective. The
      use of laparoscopic US is an integral part of the laparoscopic procedure, and the
      information achieved is valuable for both confirming localization and decision
      making concerning the most appropriate surgical procedure. In cases of distal
      pancreatectomy, splenic salvage, preferably with preservation of splenic vessels,
      is feasible albeit more demanding and can be achieved in most cases.

PMID- 15517486
TI  - Biochemical effects from treatment with bisphosphonate and surgery in patients
      with primary hyperparathyroidism.
AB  - Patients with primary hyperparathyroidism (pHPT) are sometimes treated with
      bisphosphonates (BPs) as an alternative to surgery despite sparse documentation
      of the efficacy in this disorder. It is therefore of interest to study the
      biochemical effects from BPs in patients with pHPT. A series of 21 pHPT patients
      with serum calcium levels > 2.8 mmol/L were included. One month before surgery
      the patients underwent intravenous infusions of 30 to 40 mg pamidronate. Study
      parameters were total and ionized serum calcium, intact parathormone (PTH),
      alkaline phosphatase (ALP) and isoenzymes, creatinine, osteocalcin, 25-OH vitamin
      D(3), 1,25-OH(2 )vitamin D(3), urine calcium/creatinine, and osmolality.
      Registration of hypercalcemia-related symptoms were done by questionnaire. After
      pamidronate there was a temporary reduction in serum calcium with a nadir at 6 to
      10 days. Normalization of serum calcium was achieved only by surgery. Intact PTH
      rose after pamidronate, with a maximum on day 6. Urinary calcium excretion was
      reduced after both pamidronate and surgery. ALP was reduced 30 days after
      pamidronate and also after surgery. Serum osteocalcin was not influenced by
      pamidronate. No statistically significant differences in symptoms were reported
      after treatment. In conclusion, there was a short, limited calcium-lowering
      effect from pamidronate in pHPT patients and a transient increase in PTH
      corresponding to the reduced calcium concentration. An obvious change in bone
      markers was found only after surgery. Treatment with BPs should not be considered
      an alternative to surgery, which is still the only method to cure patients with
      pHPT.

PMID- 15517487
TI  - Surgery of resectable nonfunctioning neuroendocrine pancreatic tumors.
AB  - Nonfunctioning neuroendocrine pancreatic tumors (NFNEPTs) comprise about one
      third of pancreatic endocrine tumors. Based on immunohistochemistry,
      nonfunctioning tumors are difficult to distinguish from functioning ones;
      therefore the final diagnosis is basically the result of a synopsis of pathology
      and clinical data. Owing to their incapacity to produce hormone-dependent
      symptoms, NFNEPTs are detected incidentally or because of uncharacteristic
      symptoms resulting from local or distant growth. About two-thirds of NFNEPTs are
      located in the pancreatic head, so jaundice may be a late symptom of this tumor.
      Modern diagnostic procedures are best applied by a stepwise approach: first
      endoscopic ultrasonography and computed tomography/magnetic resonance imaging
      followed by somatostatin receptor scintigraphy or positron emission tomography
      (or both). Due to significant false-positive and false-negative findings, for
      decision-making the latter should be confirmed by a second imaging modality.
      Regarding indications for surgery and the surgical approach to the pancreas,
      three pancreatic manifestations of NFNEPTs can be distinguished: (1) solitary
      benign non-multiple endocrine neoplasia type 1 (non-MEN-1); (2) multiple benign
      MEN-1; and (3) malignant NFNEPTs. Reviewing the literature and including our
      experience with 18 NFNEPTs (8 benign, 10 malignant) reported here, the following
      conclusions can be drawn: (1) Solitary benign non-MEN-1 NFNEPTs can be removed by
      enucleation or by pancreas-, spleen-, and duodenum-preserving techniques in most
      cases. The choice of surgical technique depends on the location and site of the
      tumor and its anatomic relation to the pancreatic duct. (2) With multiple benign
      MEN-1 NFNEPTs, because of the characteristics of the underlying disease a
      preferred, more conservative concept (removal of only macrolesions) competes with
      a more radical procedure (left pancreatic resection with enucleation of head
      macrolesions). Further studies are necessary to clarify the best way to balance
      quality of life (by preserving organ function) with growth control of potentially
      malignant tumors in the pancreas. (3) Malignant NFNEPTs comprise more than half
      of all NFNEPTs. Few studies have analyzed treatment strategies for localized or
      metastatic tumors. Whereas radical (including multivisceral) resection of tumors
      without distant metastases is widely accepted, the indication for radical surgery
      on metastasizing tumors has been questioned, as radical removal of the primary
      tumor may fail to increase survival. Adjuvant regimens in these tumor stages are
      mandatory and should be further optimized.

PMID- 15517488
TI  - Single center experience in primary surgery for medullary thyroid carcinoma.
AB  - Medullary thyroid carcinoma (MTC) is a rare disease, and most studies are either
      based on small numbers or multicenter studies with their inherent difficulties.
      Since 1995, a total of 440 patients with MTC underwent surgery in our clinic. A
      primary operation was performed in 188 patients (43% of 440). In 60 patients, the
      primary operation was performed because of a germline RET mutation ("prophylactic
      surgery"). Most (84%, 158/188) of the patients had pathologic calcitonin levels.
      Notably, MTC was found in almost 10% (3/30) of patients with normal calcitonin
      levels. However, all patients with lymph node metastases (LNMs) had elevated
      calcitonin levels. Total thyroidectomy (TTx) was performed in all patients. Lymph
      node dissection (LND) was performed at various extensions: one-compartment LND in
      35% (66/188), three-compartment LND in 31% (58/188), and four-compartment LND in
      29% (22/188). In general, lymph node dissection increased the likelihood of
      complications. LNM and distant metastases (DM) correlated with the extent of the
      primary tumor (pT category). The presence of LNM ranged from 17% (pT1 tumor) to
      100% (pT4 tumor), whereas the presence of DM ranged from 0% (pT1 tumor) to 81%
      (pT4 tumor). Biochemical cure (normal calcitonin levels) was obtained in 72%
      (137/188) of patients. All 60 patients undergoing prophylactic surgery (tumor
      stage pT0/pT1) were biochemically cured. In contrast, only 60% (77/128) of the
      remaining patients were cured. The data suggest that primary surgery should be
      scheduled as soon as possible to treat patients at a node-negative stage. In the
      case of normal basal and elevated stimulated calcitonin levels, TTx and
      cervicocentral LND is recommended. If the basal calcitonin level is elevated, LND
      should include the cervicolateral compartment.

PMID- 15517489
TI  - Resection and reconstruction of the airway in patients with advanced thyroid
      cancer.
AB  - The prognosis of patients with differentiated thyroid cancer is relatively fair,
      with a 10-year survival rate above 80%. One of the important prognostic factors
      is cancer invasion to the airway. For the last 25 years we have been performing
      combined resection of the trachea and larynx and have reported a relatively good
      10-year survival (67.7%) and improved quality of life (QOL). However, operative
      complications associated with the procedure, especially insufficiency of the
      anastomosis and bleeding from large vessels, are life-threatening. Of 40 patients
      who underwent resection of the trachea, insufficiency of the anastomosis occurred
      in 4 and subsequent massive bleeding from carotid artery due to neck infection in
      2. Tracheal resection should be carried out carefully by avoiding insufficiency.
      We have concluded that combined resection is a good treatment choice for survival
      and good QOL when performed for local control in patients with differentiated
      thyroid cancer.

PMID- 15517491
TI  - Modified radical neck dissection for differentiated thyroid cancer: operative
      technique.
AB  - Our standard surgical approach to patients with papillary thyroid cancer is
      subtotal thyroidectomy with modified radical neck dissection (MRND) on the
      affected side. MRND preserves the jugular vein, the sternocleidomastoid muscle,
      and the accessory nerve, effectively conserving function and cosmesis. Knowledge
      of the anatomy of the neck, precise staging, prognostic evaluation, and
      experience are needed for a surgeon to perform MRND. Radical neck dissection
      should not be performed unless the tumor invades the jugular vein and
      sternocleidomastoid muscle. Berry picking is not indicated for patients with
      thyroid cancer. The skin incision used is an extended collar incision. If lymph
      node metastasis is present at the upper bifurcation of the carotid artery, a
      modified MacFee incision is used. Taping of the carotid artery or
      sternocleidomastoid muscle is avoided unless the tumor invades these tissues.
      MRND is a safe procedure when performed by skilled, experienced surgeons.

PMID- 15517490
TI  - Current strategies for surgical management and adjuvant treatment of childhood
      papillary thyroid carcinoma.
AB  - Childhood papillary thyroid carcinoma is associated with more locally aggressive
      and more frequent distant disease than its adult counterpart. Recurrence rates
      tend to be higher in children, but cause-specific mortality remains low. Optimal
      initial treatment of childhood papillary thyroid carcinoma should include total
      or near-total thyroidectomy and central compartment node clearance. Modified neck
      dissections should be performed for biopsy-proven lateral neck disease. Every
      effort should be made to maintain parathyroid and laryngeal nerve function.
      Radical neck dissections are to be avoided. Radioiodine remnant ablation (RRA),
      appropriate thyroid hormone suppressive therapy (THST), and judicious use of
      therapeutic doses of (131)I are applied to achieve a disease-free status, which
      is most often confirmed by negative neck ultrasonography, negative whole-body
      scan (either withdrawal or recombinant human thyroid-stimulating hormone
      stimulated), and extremely low levels of serum thyroglobulin. Appropriate
      utilization of (131)I, THST, repeat surgery, external beam radiotherapy, and
      rarely chemotherapy may provide long-term palliation and some cures in patients
      with recurrent/persistent disease. Follow-up should be lifelong, and the care of
      children after age 17 should subsequently be transferred to adult-care
      endocrinologists with expertise in managing thyroid neoplasia. Optimal surgical
      management can be achieved if adequate operations are routinely carried out by
      "high-volume" thyroid surgeons with expertise in the care of children. Nowhere is
      a multidisciplinary approach (endocrinologists, surgeons, nuclear medicine
      physicians, pediatricians, pathologists, oncologists) more critical than in the
      long-term management of papillary thyroid carcinoma that presents during
      childhood.

PMID- 15517492
TI  - Prognostic indications for Hurthle cell cancer.
AB  - Hurthle cell carcinoma (HCC) has been reported to have variable clinical
      behavior. The objective of this study was to determine the important prognostic
      factors in patients with HCC. It was a retrospective investigation of 33 patients
      with HCC treated in our institution from 1976 to 2002. The average age of our 33
      patients with HCC was 55.2 years (range 20-82 years; 23 women, 10 men). Fifteen
      patients (45.5%) presented with a T2 tumor, 7 (21.2%) with a T3 tumor, and 8
      (24.2%) with a T4 tumor; the tumor stage was unknown in three patients.
      Coexisting papillary carcinoma occurred in six patients (18%), 9% of whom
      presented with metastatic disease. Twelve patients (36.4%) had metastases, four
      of whom (12.2%) had persistent HCC, and 8 (24.2%) developed recurrent HCC (range
      1-9 years). Eight of these twelve patients (66.7%) died from the HCC. The average
      follow-up time was 5.5 years (range 1-16 years). Altogether, 3 of 23 women and 5
      of 10 men died from their HCC ( p < 0.05). Of the 22 patients with T2-T3 tumors,
      5 (22.7%) developed metastases and 1 patient died; 5 of 8 patients (62.5%) with
      T4 tumors developed metastases and died ( p < 0.01). Patients who were treated by
      less than total thyroidectomy had a worse prognosis by univariate analysis ( p <
      0.01) but not by multivariate analysis. Survival time for patients with
      persistent disease was shorter than for those with recurrent disease ( p < 0.05).
      Multivariate analysis, however, revealed no difference for extent of operation or
      those with persistent and recurrent disease. The cause-specific survivals were
      74% and 49% at 5 and 10 years, respectively. Disease-free survivals were 65.0%
      and 40.5% at 5 and 10 years, respectively. Our findings show that gender and
      stage of disease influence the prognosis of patients with HCC.

PMID- 15517493
TI  - Endoscopic parathyroid surgery: results of 365 consecutive procedures.
AB  - In recent years, several series have documented the feasibility of endoscopic
      approaches for parathyroid diseases. We performed a retrospective study to
      evaluate the results of endoscopic parathyroidectomy (EP) in the management of
      our patients with primary hyperparathyroidism (PHPT). During a 5.5 year period
      (1998-2003), we operated on 644 patients with PHPT. EP was proposed for patients
      with sporadic PHPT, without associated goiter, and without previous neck surgery
      in whom a single adenoma was localized by means of sonography and sestamibi
      scanning. EP was performed by the lateral approach with insufflation for patients
      with an adenoma located deep in the neck and by a gasless midline approach for
      patients whose adenoma was located anteriorly. A quick parathyroid (QPTH) assay
      was used during the surgical procedures. Among 644 patients with PHPT, 279
      (43.3%) were not eligible for EP for the following reasons: associated nodular
      goiter (116 cases), previous neck surgery (52 cases), suspicion of multiglandular
      disease (31 cases), lack of preoperative localization (61 cases), and
      miscellaneous causes (19 cases). EP was performed in 365 patients with sporadic
      PHPT: 339 lateral access, 25 midline access, and one thoracoscopy. The median
      operating time was 49 minutes (16-130 minutes). Conversion to conventional
      parathyroidectomy was required in 49 patients (13.4%) for these reasons: missed
      adenomas (14 cases), difficulty with the dissection (8 cases), multiglandular
      disease correctly predicted by QPTH (11 cases), false-negative QPTH assay results
      (4 cases), false-positive sestamibi scan results (11 cases), and 1 false-positive
      sonography result. One patient presented with definitive recurrent nerve palsy.
      Three patients remained hypercalcemic, and one other patient had recurrent
      hypercalcemia. In conclusion, EP can be proposed for more than half of the
      patients with PHPT. Immediate results of EP are similar to those obtained with
      conventional parathyroidectomy, but no conclusions can be drawn in terms of the
      influence of EP on the outcome of the patients operated on for PHPT.

PMID- 15517494
TI  - Open minimally invasive parathyroid surgery.
AB  - Outpatient minimally invasive parathyroidectomy (MIP) employs (1) preoperative
      parathyroid localization with high quality sestamibi scans, (2) cervical block
      anesthesia, (3) limited exploration, and (4) the rapid intraoperative parathyroid
      hormone assay to confirm an adequate resection. The technical aspects of this
      procedure are described, and the results obtained in 255 patients who underwent
      MIP are compared with those of 401 patients who underwent conventional bilateral
      cervical exploration under general anesthesia. MIP and standard exploration were
      indistinguishable with regard to high cure and low complication rates. MIP,
      however, was superior with regard to operating time, length of hospital stay,
      patient comfort, and costs.

PMID- 15517496
TI  - Clinical evaluation of color Doppler imaging for the differential diagnosis of
      thyroid follicular lesions.
AB  - Ultrasonography (US) of the thyroid gland has recently proved to be a useful
      clinical diagnostic method, and the newly developed high-resolution US with a
      color Doppler flow mapping function can reveal fine details of the thyroid gland
      and the hemodynamic features of a thyroid neoplasm. US can yield a diagnostic
      accuracy of more than 90% for thyroid carcinoma, especially papillary carcinoma.
      However, neither conventional B-mode US imaging nor aspiration biopsy cytology
      has delivered satisfactory results for follicular carcinoma. The aim of this
      study was to evaluate the clinical usefulness of color Doppler imaging for the
      differential diagnosis of thyroid follicular lesions. A color Doppler scan was
      performed in 310 patients with a solitary cold nodule, and a combination of B
      mode US and color Doppler findings, including tumor vascularity and results of a
      fast Fourier transform (FFT) analysis were used to create the following
      diagnostic grading system for differential diagnosis of follicular lesions: grade
      1, benign follicular lesion [no color flow mapping (CFM) inside the nodule];
      grade 2, benign peripheral type [CFM only in peripheral area, pulsatility index
      (PI) < 1.0]; grade 3, suspected follicular carcinoma (penetrating CFM,
      vascularity moderate); grade 4, follicular carcinoma (high-velocity penetrating
      CFM, PI = 1.0). All patients were subjected to surgical resection, and histologic
      examination was used to confirm the diagnosis. The grades of the 177 adenomatous
      nodules were as follows: grade 1, 46.9%; grade 2, 48.0%; grade 3, 5.1%; grade 4,
      0%. The corresponding percentages for the 89 follicular adenomas were 16.9%,
      49.4%, 30.3%, and 3.4%; and for the 44 follicular carcinomas they were 0%, 13.6%,
      45.5%, and 40.9%. On the assumption that grade 1 and 2 lesions are benign and
      grade 3 and 4 lesions are malignant, 38 of the 44 follicular carcinomas and 227
      of the 266 benign tumors had been accurately diagnosed, yielding a sensitivity of
      88.9%, a specificity of 74.2%, and an accuracy of 81.0% for the grading system.
      Color Doppler imaging of 310 follicular tumors has revealed that high-velocity
      pulsatile blood flow penetrating the tumor is a characteristic finding of
      follicular carcinoma and is a new diagnostic criterion for performing color
      Doppler imaging. The differential diagnostic grading scores for color Doppler
      examinations and the results of FFT analysis demonstrate that US with the color
      Doppler function can play an important role in the differential diagnosis of
      thyroid tumors.

PMID- 15517495
TI  - Nesidioblastosis: an old term and a new understanding.
AB  - Nesidioblastosis is a clinically, pathologically, and genetically heterogeneous
      disease. Differences between well described forms in neonates with persistent
      hyperinsulinemic hypoglycemia of infancy (PHHI) and rare forms in adults are
      described. Histopathologic criteria include hypertrophic islets occasionally
      showing beta cells with pleomorphic nuclei, ductuloinsular complexes, and
      neoformation of islets from ducts. These changes can be found as diffuse or focal
      forms of nesidioblastosis. Although most cases occur sporadically, several
      genetic defects ( SUR1, Kir6.2, GCK, and GLUD1 genes) have been described in
      neonates. In adults a higher rate of nesidioblastosis is observed in conjunction
      with multiple endocrine neoplasia type 1. The disease is diagnosed biochemically
      by a supervised fasting test in adults and in neonates by determining the glucose
      requirements to maintain normoglycemia, inappropriately high insulin and c
      peptide levels, low free fatty acid and ketone body concentrations, glycemic
      response to glucagons, and the absence of ketonuria. If all highly selective
      noninvasive imaging techniques fail to identify a tumor, selective arterial
      calcium stimulation testing for gradient-guided surgery in adults and
      percutaneous transhepatic pancreatic venous sampling in neonates should be
      performed. a 95% pancreatectomy is necessary in neonates with a diffuse form of
      nesidioblastosis, whereas focal forms can be treated by partial pancreatectomy.

PMID- 15517499
TI  - Treatment of malignant lymphoma.
AB  - Malignant lymphomas are increasing in frequency for unknown reasons. We know
      today that they constitute a big family of tumours of lymphoproliferative origin,
      which can be very different one from the other in terms of morphology, biology,
      and clinical behaviour. Some of them need very specific treatments and it is
      therefore important that a clear diagnosis is obtained and that the treatment is
      administered by specialised doctors. Although the new WHO classification has
      abolished the concepts of low-grade and high-grade lymphomas, it remains true
      that some lymphomas exhibit indolent behaviour and cannot be cured, while other
      aggressive lymphomas can be cured by modern therapy. The cornerstone of treatment
      remains chemotherapy and, to a minor extent, radiotherapy. New treatment
      modalities such as the use of monoclonal antibodies, high-dose therapy or
      allogenic transplantation have improved the treatment results in the last decade.
      In this article we offer a summary of the most important concepts which are of
      interest for practising physicians.

PMID- 15517500
TI  - Antibiotic misuse in medium-sized Swiss hospitals.
AB  - Antibiotics account for a substantial proportion of hospital drug expenditures
      and tend to be misused or overused, generating unnecessary costs and causing the
      emergence of resistant bacteria. Antibiotic use was evaluated in a one-day
      prevalence study performed on the surgical and medical wards of eight Swiss non
      university hospitals. 173 of the 695 inpatients present (25%) were on antibiotics
      and 163 could be evaluated. 35 prescriptions were secondary to an infectious
      disease consultation. 60 of the remaining 128 (47%) were considered
      inappropriate, of which 17 (28%) lacked any indication for antibiotic use. The
      rates of misuse were higher in surgery than in medicine (58 vs. 34%; OR = 2.5
      [95% CI: 1.1-5.9]), and higher for prophylaxis than for treatment (72 vs. 41%; OR
      = 4.1 [95% CI: 1.3-15.5]). Savings of 545 euros (95% CI: from -116 to 1,206
      euros) on the study day and 6,256 euros (95% CI: from -2,221 to 14,732 euros) for
      the total treatments or prophylaxis administered would have resulted from
      infectious disease consultations.

PMID- 15517497
TI  - Unilateral surgery for hyperparathyroidism: indications, limits, and late results
      -new philosophy or expensive selection without improvement of surgical results?
AB  - We assessed the "late" results after unilateral parathyroidectomy (PTX) performed
      for selected indications. From October 1998 throughout March 2001 we operated on
      454 patients for hyperparathyroidism (HPT). A positive unifocal (99m)tc-MIBI scan
      was required for the unilateral approach to be used. Intact parathormone (PTH)
      measurements were done intraoperatively. Postoperative calcium and PTH serum
      levels of unilaterally operated patients were checked. Follow-up has been 16.2
      months (range 6-40 months). Of the 454 patients, 336 (74.0%) were not eligible
      for the unilateral approach; and 125 (27.5%) of the 454 patients had renal HPT.
      Among the 329 patients with primary HPT, 125 (38.0%) were excluded for well
      established reasons, and in 77 other cases (23.5%) preoperative imaging results
      did not allow the unilateral approach. Altogether, 126 patients (38.3%) with
      primary HPT were selected for the unilateral approach. Of the 126 unilateral
      operations, 8 (6.3%) had to be converted to a bilateral procedure. Among the 118
      patients with a unilateral approach, 3 patients have been reoperated for
      overlooked contralateral disease, and 13 dropped out of the study. A total of 102
      postoperative calcium and PTH serum late levels are known: 90 (88.2%) patients
      had normal levels; 10 (9.8%) had a high PTH level, and 2 (1.9%) had high ionized
      calcium levels. The failure rate in selected cases was 4.2% (5/118) (three were
      reoperated, and two had a supranormal postoperative ionized Ca level). Even with
      stringent indications, the late results of unilateral surgery (95.8% cure rate)
      barely matched those of conventional bilateral surgery (97.6% cure rate). The
      economic impact of such a surgical strategy should be clarified.

PMID- 15517501
TI  - Management and evolution of insomnia complaints among non-substance-misusers in a
      Swiss remand prison.
AB  - QUESTIONS UNDER STUDY: Insomnia is a frequent though rarely investigated problem
      among prisoners. The study's aim was to examine the clinical management of
      insomnia complaints in non-substance-misusing (NSM) prisoners (quality of medical
      consultation, effectiveness of drug prescription), and the risk of leaving prison
      with ongoing hypnotic prescription which might provoke withdrawal symptoms and
      encourage further hypnotic use outside prison. METHODS: Retrospective study of
      the medical records of 112 NSM prisoners complaining of insomnia at medical
      consultation over a one year period at the outpatient-service of the Champ-Dollon
      remand prison (Geneva, Switzerland). We examined insomnia management by the
      general practitioners (anamnestic and clinical evaluation documented in the
      record), type, duration and effectiveness of treatment. RESULTS: The 112 records
      show a prescription of hypnotics to 111 patients (80% benzodiazepines or
      Zolpidem), a limited documented insomnia work-up (anamnestic information about
      sleep habits, sleep latency and previous hypnotic use for less than a third of
      the patients, about the impact of insomnia, such as fatigue, on daily activity in
      only 7%). In more than 60% of the patients, insomnia complaints persisted for
      more than 3 weeks. In 41 (37%) patients, improvement (defined subjectively based
      on patients' complaints) was complete, in 20 (18%) absent, and in 34 (30%)
      incomplete while taking the prescribed hypnotics. Patients without or with only
      partial improvement of insomnia received the highest number of hypnotics (mean
      2.4, vs. 1.4 for patients with total improvement, 95% CI of the difference: 0.7
      1.4). 55% of the 112 prisoners left prison with hypnotics still being prescribed.
      CONCLUSIONS: Our results show that prison physicians' evaluation for insomnia was
      incomplete. Drug prescription did not seem to have been an effective treatment
      for insomnia complaints in a sizeable number of patients. Many prisoners leave
      the prison with benzodiazepine prescription still ongoing and could be at risk
      for continued hypnotic use following imprisonment.

PMID- 15517502
TI  - Are environmental medicine problems relevant in Switzerland?
AB  - BACKGROUND AND AIM: In Switzerland, the prevalence of health problems attributed
      to environmental exposures is unknown, and views differ regarding its magnitude.
      In the present study we investigated the frequency of environmentally related
      health problems amongst the patients of Swiss sentinel physicians and assessed
      symptoms and suspected environmental exposures. METHODS: During 2002, nearly 250
      "Swiss Sentinel Surveillance Network" physicians were asked to record the number
      of patients presenting with environmental health problems and to complete a
      questionnaire inquiring about suspected environmental exposures and health
      problems. Physicians offering "alternative" medical therapies also participated
      in the study. The results were compared with the experience of a Basel University
      pilot project which evaluated patients with environment-related health problems
      simultaneously from the medical, psychiatric and environmental viewpoint.
      RESULTS: 354 environment-related consultations were reported by 72 physicians,
      corresponding to 0.03% of all sentinel-physician consultations. There were
      considerable differences both within the group of Sentinella physicians, and
      between physicians offering "alternative" medical therapies and the Sentinella
      physicians, in the frequency of environmentally-related consultations, the
      character of the reported symptoms and the suspected environmental exposures.
      CONCLUSION: Overall, environmental medicine consultations in general practice
      were rare. However, experience of the environmental medicine pilot project showed
      that concerned persons seek help from various health care providers and from
      environmental agencies. Effective treatment should include counselling by
      medical, psychiatric and environmental professionals.

PMID- 15517503
TI  - Childhood nutritional status: ongoing surveillance is necessary.

PMID- 15517504
TI  - Heart rate variability: a noninvasive electrocardiographic method to measure the
      autonomic nervous system.
AB  - The autonomic nervous system (ANS) plays an important role not only in
      physiological situations, but also in various pathological settings such as
      diabetic neuropathy, myocardial infarction (MI) and congestive heart failure
      (CHF). Autonomic imbalance associating increased sympathetic activity and reduced
      vagal tone has been been strongly implicated in the pathophysiology of
      arrhythmogenesis and sudden cardiac death. Among the different available
      noninvasive techniques for assessing the autonomic status heart rate variability
      (HRV) has emerged as a simple, noninvasive method to evaluate the sympathovagal
      balance at the sinoatrial level. It has been used in a variety of clinical
      situations including diabetic neuropathy, MI, sudden death and CHF. The standard
      measurements intervening in the analysis of HRV comprise time domain indices,
      geometric methods and components of the frequency domain. Measurements of HRV are
      generally performed on the basis of 24 hour Holter recordings (long-term
      recordings) or on shorter periods ranging from 0.5 to 5 minutes (short-term
      recordings). The use of long or short-term recordings depends on the type of
      study that has to be realised. Established clinical data based on numerous
      studies published during the last decade consider decreased global HRV as a
      strong predictor of increased all-cause cardiac and/or arrhythmic mortality,
      particularly in patients at risk after MI or with CHF. This article reviews the
      mechanism, the parameters and the use of HRV as a marker reflecting the activity
      of the sympathetic and vagal components of the ANS on the sinus node, and as a
      clinical tool for screening and identifying patients particularly at risk for
      cardiac mortality.

PMID- 15517505
TI  - Overweight and obesity in 6-12 year old children in Switzerland.
AB  - OBJECTIVES: Our aim was to estimate the national prevalence of overweight and
      obesity in Swiss primary schoolchildren and to determine if adiposity is
      increasing in this age group. METHODS: We used a cross-sectional, 3-stage,
      probability-proportionate-to-size cluster sampling of primary schools throughout
      Switzerland to obtain a representative national sample of 6-12 year old children
      (n = 2431). Height and weight were measured and used to calculate body mass index
      (BMI). BMI references from the U.S. Centers for Disease Control and Prevention
      (CDC) and the International Obesity Task Force (IOTF) were used to define
      adiposity. The triceps, biceps, subscapular and suprailiac skinfold thickness
      (SFT) was measured and used to calculate body fat percentage (BF%). BMI and BF%
      were compared to data from 6-12 year old Swiss children in the 1960's and 1980's.
      RESULTS: BMI and BF% were well correlated in both boys and girls (r2 = 0.74).
      Using the IOTF references, the prevalence of overweight and obesity was 16.6% and
      3.8% in boys and 19.1% and 3.7% in girls. Using the CDC references, the
      prevalence of overweight and obesity was 19.9% and 7.4% in boys and 18.9% and
      5.7% in girls. There was no significant age or gender difference in the
      prevalence of overweight or obesity. At all ages, boys and girls had 50-100%
      higher mean BF% than Swiss children from the 1960's and 1980's. Using the current
      CDC BMI references, the prevalence of overweight has increased more than 5-fold
      in Swiss children since the mid-1980's. CONCLUSIONS: These findings suggest there
      has been a striking increase in BF% and the prevalence of overweight and obesity
      in Swiss children in the last two decades.

PMID- 15517506
TI  - Prevalence of underweight, overweight and obesity in Turkish adolescents.
AB  - BACKGROUND: The aim of this study was to determine underweight, overweight and
      obesity prevalence in a representative sample of adolescents living in urban and
      rural area of central Edirne, Turkey, and to compare the 95th percentile BMI
      curve to the curves of other countries. MATERIAL AND METHODS: Data concerning the
      height and weight of 989 adolescents, aged between 12 and 17 years were
      collected. The prevalence of underweight was defined as the percentage of
      adolescents below the 5th percentiles of the American adolescents' age and gender
      specific BMI; prevalence of overweight and obesity were based on the cut off
      points of the International Obesity Task Force values (excess of the 85th and
      95th percentiles), respectively. RESULTS: This study demonstrated that the
      prevalence of underweight, overweight and obesity among adolescent girls was
      11.1%, 10.6% and 2.1%, respectively, while it was 14.4%, 11.3% and 1.6% for
      adolescent boys. In the urban area the prevalence of underweight, overweight and
      obesity among adolescent girls was 10.0%, 10.3% and 2.1%, while it was 14.4%,
      11.6% and 1.6% for boys, respectively. In the rural area; the prevalence of
      underweight, overweight and obesity among adolescent girls was 15.7%, 12.4% and
      2.2%, while it was 14.5%, 9.6% and 1.2% for boys, respectively. DISCUSSION:
      Analyses of data collected during these studies support that adolescents living
      in the city of Edirne carry relatively lower further risk of overweight and
      obesity than adolescents in other countries do.

PMID- 15517507
TI  - Gamma-hydroxybutyrate (GHB) and gamma-butyrolactone (GBL): analysis of overdose
      cases reported to the Swiss Toxicological Information Centre.
AB  - We analysed 141 cases of Gamma-hydroxybutyric acid (GHB) and Gamma-butyrolactone
      (GBL) intoxication reported by physicians to the Swiss Toxicological Information
      Centre between 1995 and 2003. GHB and GBL intoxication are associated with
      considerable morbidity. Multiple drug use is common. Overdosing frequently
      results in non-reactive coma, which accounts for the severity of the intoxication
      and the costs occasioned by management.

PMID- 15517512
TI  - Formulation substitution: a frequently overlooked variable in cardiovascular drug
      management.

PMID- 15517513
TI  - Cardiovascular drug class specificity: beta-blockers.
AB  - Beta-adrenergic blockers are one of the most frequently prescribed cardiovascular
      drugs. Numerous beta-blockers are available for clinical use. Although these
      agents differ substantially, it is not clear whether (and which) differences are
      clinically relevant. Most of the important differences among agents reflect the
      relative specificity for beta1-, beta2-, and alpha-adrenergic receptors.
      Selection of a particular agent and target dose is probably best guided by
      available trial data, even though data are limited. Nonselective agents (with or
      without alpha-blocking properties) devoid of intrinsic sympathetic activity (ISA)
      are most appropriate postinfarction. Evidence exists demonstrating a mortality
      benefit postinfarction for propranolol, timolol, metoprolol, and, in the presence
      of left ventricular dysfunction, carvedilol. In the setting of heart failure, the
      selective agents metoprolol and bisoprolol as well as the nonselective agent
      carvedilol (which possesses alpha-blocking properties) have a demonstrated
      mortality benefit. Not all tolerated beta-blockers are associated with a survival
      benefit and it is probably not advisable to extrapolate benefits to all drugs
      with similar (although probably not identical) properties. Carvedilol may possess
      advantages over other beta-blockers and a possible survival advantage, suggested
      by the recent Carvedilol or Metoprolol European Trial (COMET), although these
      findings are not universally accepted. Ultimately, selection of a specific agent
      avoids obvious contraindications and uses trial data to guide selection and dose
      as long as side effects are absent or tolerable.

PMID- 15517514
TI  - Calcium antagonists.
AB  - Calcium antagonists were introduced for the treatment of hypertension in the
      1980s. Their use was subsequently expanded to additional disorders, such as
      angina pectoris, paroxysmal supraventricular tachycardias, hypertrophic
      cardiomyopathy, Raynaud phenomenon, pulmonary hypertension, diffuse esophageal
      spasms, and migraine. Calcium antagonists as a group are heterogeneous and
      include 3 main classes--phenylalkylamines, benzothiazepines, and dihydropyridines
      -that differ in their molecular structure, sites and modes of action, and effects
      on various other cardiovascular functions. Calcium antagonists lower blood
      pressure mainly through vasodilation and reduction of peripheral resistance. They
      maintain blood flow to vital organs, and are safe in patients with renal
      impairment. Unlike diuretics and beta-blockers, calcium antagonists do not impair
      glucose metabolism or lipid profile and may even attenuate the development of
      arteriosclerotic lesions. In long-term follow-up, patients treated with calcium
      antagonists had development of less overt diabetes mellitus than those who were
      treated with diuretics and beta-blockers. Moreover, calcium antagonists are able
      to reduce left ventricular mass and are effective in improving anginal pain.
      Recent prospective randomized studies attested to the beneficial effects of
      calcium antagonists in hypertensive patients. In comparison with placebo, calcium
      antagonist-based therapy reduced major cardiovascular events and cardiovascular
      death significantly in elderly hypertensive patients and in diabetic patients. In
      several comparative studies in hypertensive patients, treatment with calcium
      antagonists was equally effective as treatment with diuretics, beta-blockers, or
      angiotensin-converting enzyme inhibitors. From these studies, it seems that a
      calcium antagonist-based regimen is superior to other regimens in preventing
      stroke, equivalent in preventing ischemic heart disease, and inferior in
      preventing congestive heart failure. Calcium antagonists are also safe and
      effective as first-line or add-on therapy in diabetic hypertensive patients.
      Heart rate-lowering calcium antagonists (verapamil, diltiazem) may have an edge
      over the dihydropyridines in post-myocardial infarction patients and in diabetic
      nephropathy. Thus, calcium antagonists may be safely used in the management of
      hypertension and angina pectoris.

PMID- 15517515
TI  - Outcomes of thrombolytic therapy for acute myocardial infarction in women.
AB  - Coronary artery disease is the leading cause of mortality in women older than 50
      years of age. Thrombolytic therapy substantially reduces mortality in both women
      and men with ST-elevation acute myocardial infarction. However, the mortality
      risk reduction is somewhat lower in women, in spite of similar rates of
      successful coronary reperfusion after thrombolytic therapy in women and men.
      Hemorrhagic complications including stroke and other major bleeding appear to be
      more common in women, particularly elderly women. The risk of reinfarction after
      thrombolytic therapy also is greater in women compared with men. Because of the
      higher complication rates, women should be monitored closely after thrombolytic
      therapy. However, this lifesaving treatment should not be withheld or delayed in
      women when indicated.

PMID- 15517517
TI  - Hands that heal--hands that harm.

PMID- 15517521
TI  - Linking the sepsis triad of inflammation, coagulation, and suppressed
      fibrinolysis to infants.
AB  - Sepsis continues to be a significant cause of morbidity and mortality in
      hospitalized newborns and premature infants. The pathophysiology and disease
      state of sepsis appear to be similar between adults and children. Both groups
      display symptoms that indicate a systemic inflammatory response leading to
      coagulopathy, hypotension, inadequate perfusion of peripheral tissues and organs,
      and, ultimately, organ failure and death. By presenting a comparison of adult and
      neonatal pathophysiology, as well as a supporting literature review and clinical
      evidence, this article links the pathways of inflammation, activation of
      coagulation, and impaired fibrinolysis, known as the sepsis cascade, to neonatal
      sepsis. Knowledge of the pathophysiology has important clinical and research
      implications. Unlike traditional antimicrobial therapy, new potential therapies,
      currently under investigation for the treatment of sepsis, target the cellular
      response rather than the invading organism. A more complete understanding of the
      pathophysiology of sepsis may also lead to diagnostic tools with improved
      sensitivity and specificity for early recognition and treatment.

PMID- 15517522
TI  - Prenatal attachment and other correlates of postnatal maternal attachment to
      twins.
AB  - PURPOSE: To determine the relationship of prenatal attachment and other selected
      perinatal contextual variables (method of delivery, maternal self-reported
      health, depression, infant birthweight, need for neonatal intensive care unit
      [NICU] admission) to postnatal attachment in mothers of twins. SUBJECTS: Two
      hundred fourteen women were initially recruited from a national mothers of twins
      support group for a study of maternal prenatal attachment. Of the 168 women who
      agreed to be contacted after delivery, 142 returned completed questionnaires
      (82.7% response rate), with 139 study-eligible women included in the analysis for
      this report. STUDY DESIGN: Correlational design with longitudinal follow-up at 1
      month after expected delivery date. METHODS: Self-administered, mailed
      questionnaires completed by women with twin gestations prenatally and postnatally
      1 month after their expected delivery dates. Descriptive analysis, correlations,
      and regression equations were performed. MAIN OUTCOME MEASURES: The Maternal
      Attachment Inventory. PRINCIPLE RESULTS: A modest correlation was found between
      prenatal and postnatal attachment ( r = 0.38, P < 0.001). Prenatal attachment and
      postpartum depression explained 26.1% of the variance in postnatal attachment ( F
      = 5.06, P < 0.001). Depression, method of delivery, and need for admission to the
      NICU had moderator effects on the relationship between prenatal attachment and
      postnatal attachment. The addition of these interaction terms nominally increased
      the adjusted R 2 to explain 27.9% to 29.6% of the variance in postnatal
      attachment. CONCLUSIONS: Although the study findings support a modest
      relationship between prenatal and postnatal attachment in mothers of twins,
      maternal depression was also significant in explaining postnatal attachment.
      Postpartum depression, having a cesarean delivery, and the experience of a NICU
      admission for 1 or both twins further influenced the relationship between
      prenatal attachment and postnatal attachment. When fostering attachment in
      mothers of twins, nurses should assess for symptoms of depression and pay
      particular attention to those women who have an infant requiring a NICU
      admission.

PMID- 15517523
TI  - Developing a strategic plan for a neonatal nurse practitioner service.
AB  - Neonatal nurse practitioners (NNPs) have been in practice for over 3 decades.
      More recently, NNPs have begun to take ownership for building their group
      practice models. The purpose of this article is to present a detailed case study
      demonstrating how one NNP group used a 4-phase strategic planning process to turn
      a crisis into an opportunity. The article describes data obtained during the
      strategic planning process from an informal national survey of NNP managers that
      focused on key benchmarks, such as role definition, responsibilities, protected
      nonclinical time, NNP salary and benefits, and educational and professional
      development support. Using the strategic planning process, the group defined
      mutually agreed upon minimum safe staffing levels for NNPs, interns, residents
      and neonatologists in their setting. Based on the data generated, the group
      successfully justified additional NNP positions and organizational support for
      10% protected nonclinical time. A sample operational budget, comparison of 3
      staffing scenarios, and a timeline are also provided.

PMID- 15517524
TI  - A primer on newborn screening.
AB  - Metabolic disorders are individually rare, but when considered together as a
      disease entity are relatively frequent, occurring in 1 in 1000 to 1 in 3000
      infants. Some disorders can have devastating and irreversible outcomes if not
      diagnosed early and treated promptly. Newborn screening is a vital step in
      identifying infants with inborn metabolic disorders, hemoglobinopathies,
      infectious processes, and congenital endocrinopathies; the goal is early
      recognition and treatment. This article summarizes the critical aspects of
      newborn screening, comparing and contrasting current national screening
      practices, and identifying key considerations for clinical care, parental
      education, and support. To prevent morbidity and mortality, healthcare providers
      must understand the purpose and guidelines for newborn screening. Providers are
      also responsible for informing parents about the implications of newborn
      screening to improve awareness and understanding.

PMID- 15517525
TI  - Family teaching toolbox. A parent's guide to newborn screening.

PMID- 15517526
TI  - Quantitative determination of the novel anticancer drug E7070 (indisulam) and its
      metabolite (1,4-benzenedisulphonamide) in human plasma, urine and faeces by high
      performance liquid chromatography coupled with electrospray ionization tandem
      mass spectrometry.
AB  - E7070 (indisulam) is a novel anticancer drug currently undergoing clinical
      investigation. We present a sensitive and specific method for the quantitative
      determination of E7070 and its metabolite M1 (1,4-benzenedisulphonamide) in human
      plasma, urine and faeces. The analytes and their tetra-deuterated analogues,
      which were used as internal standards, were isolated from the biological matrix
      by solid-phase extraction with OASIS cartridges (0.5 mL plasma or 1 mL urine) and
      by liquid-liquid extraction with ethyl acetate at pH 5 (1 mL faecal homogenate).
      The analytes were separated on a C8 reversed-phase chromatographic column and
      analyzed using electrospray ionization and tandem mass spectrometric detection in
      the negative ion mode. The validated concentration ranges in plasma were 0.1-20
      microg/mL for E7070 and 0.01-2 microg/mL for M1. In urine and faecal homogenate,
      a concentration range from 0.05-10 microg/mL or microg/g, respectively, was
      validated for both analytes. Validation of the plasma assay was performed
      according to the most recent FDA guidelines. The assay fulfilled all generally
      accepted requirements for linearity (r > 0.99, residuals between -8 and 10%),
      accuracy (-13.5 to 1.4%) and precision (all less than 11%) in the tested
      matrices. We investigated recovery, stability (working solutions at -20 degrees C
      and at room temperature, biological matrices at -20 degrees C, room temperature
      and after 3 freeze/thaw cycles; final extracts at room temperature) and
      robustness. All these parameters were found acceptable. This method is suited for
      mass balance studies or therapeutic drug monitoring, as demonstrated by a case
      example showing plasma concentrations and cumulative excretion of E7070 and M1 in
      urine and faeces. Furthermore, we show the presence of E7070 metabolites in
      patient urine.

PMID- 15517527
TI  - Stable carbon and oxygen isotopic determination of sub-microgram quantities of
      CaCO3 to analyze individual foraminiferal shells.
AB  - We have developed an analytical system to determine stable isotopic compositions
      (delta13C and delta18O) of sub-microgram quantities of CaCO3 for the purpose of
      analyzing individual foraminiferal shells, using continuous-flow isotope ratio
      mass spectrometry (CF-IRMS). The system consists of a micro-volume CaCO3
      decomposition tube, stainless steel CO2 purification vacuum line with a quantity
      regulating unit, helium-purged CO2 purification line, gas chromatograph, and a CF
      IRMS system. By using this system, we can determine stable carbon and oxygen
      isotopic compositions as low as 0.2 microg of CaCO3, with standard deviations of
      +/-0.10 per thousand for delta13C and +/-0.18 per thousand for delta18O within a
      4-h reaction time and 30-min analysis period.

PMID- 15517528
TI  - On-line analysis of diesel engine exhaust gases by selected ion flow tube mass
      spectrometry.
AB  - Selected ion flow tube mass spectrometry (SIFT-MS) has been used to analyse on
      line and in real time the exhaust gas emissions from a Caterpillar 3304 diesel
      engine under different conditions of load (idle and 50% of rated load) and speed
      (910, 1500 and 2200 rpm) using three types of fuel: an ultra-low-sulphur diesel,
      a rapeseed methyl ester and gas oil. SIFT-MS analyses of the alkanes, alkenes and
      aromatic hydrocarbons in the headspace of these fuels were also performed, but
      the headspace of the rapeseed methyl ester consists mainly of methanol and a
      compound with the molecular formula C4H8O. The exhaust gases were analysed for NO
      and NO2 using O2+* reagent ions and for HNO2 using H3O+ reagent ions. The
      following aldehydes and ketones in the exhaust gases were quantified by using the
      combination of H3O+ and NO+ reagent ions: formaldehyde, acetaldehyde, propenal,
      propanal, acetone, butanal, pentanal, butanone and pentanone. Formaldehyde,
      acetaldehyde and pentenal, all known respiratory irritants associated with
      sensitisation to asthma of workers exposed to diesel exhaust, are variously
      present within the range 100-2000 ppb. Hydrocarbons in the exhaust gases
      accessible to SIFT-MS analyses were also quantified as total concentrations of
      the various isomers of C3H4, C3H6, C4H6, C5H8, C5H10, C6H8, C6H10, C7H14, C6H6,
      C7H8, C8H10 and C9H12.

PMID- 15517529
TI  - Simultaneous determination of magnesium lithospermate B, rosmarinic acid, and
      lithospermic acid in beagle dog serum by liquid chromatography/tandem mass
      spectrometry.
AB  - A rapid, sensitive and specific isocratic liquid chromatography/tandem mass
      spectrometry (LC/MS/MS) method was developed for the simultaneous quantitative
      determination of magnesium lithospermate B (MLB), rosmarinic acid (RA), and
      lithospermic acid (LA) in beagle dog serum, with silibinin as internal standard.
      The serum samples were treated by liquid-liquid extraction and analyzed using
      LC/MS/MS with a TurboIonSpray source. A short run-time (3 min) fulfilled the need
      for monitoring serum levels of MLB, RA, and LA in large-scale studies. The
      calibration curves for MLB, RA, and LA were linear over the ranges 8-2048, 4
      1024, and 4-1024 ng/mL, respectively, with coefficients of correlation >0.999.
      The intra- and inter-day precision (CV) of analysis was <10%, and accuracy ranged
      from 90-104%. This quantitation method was successfully applied to a
      pharmacokinetic study of salvianolate administrated by intravenous infusion with
      dosage of 6 mg/kg in beagle dogs.

PMID- 15517530
TI  - Stable oxygen isotopes from theropod dinosaur tooth enamel: interlaboratory
      comparison of results and analytical interference by reference standards.
AB  - Although previous work has demonstrated that biological phosphates
      ('biophosphates') record significant changes in delta18O associated with
      variations in local climate and seasonality, the repeatability of these analyses
      between laboratories has not previously been tested. We serially sampled enamel
      on four Cretaceous dinosaur teeth for phosphate delta18O analysis at up to three
      different facilities. With the exception of one set of unprocessed enamel
      samples, the material supplied to each laboratory was chemically processed to
      silver phosphate. Each laboratory analyzed sample sets by pyrolysis
      (thermochemical decomposition) in a ThermoFinnigan TC/EA attached to a
      ThermoFinnigan Delta Plus mass spectrometer. Significant interference between
      phosphate samples and the NIST reference material 8557 barium sulfate (NBS 127)
      distorts some of the results. Samples analyzed immediately following NBS 127 may
      be depleted by 6 per thousand isotopically and in instrument peak amplitude
      response by 80%. Substantial interference can persist over the subsequent 20
      silver phosphate samples, and can influence the instrument peak amplitude
      response from some organic standards. Experiments using reagent-grade silver
      phosphate link these effects to divalent cations, particularly Ca2+ and Ba2+,
      which linger in the reactor and scavenge oxygen evolved from pyrolysis of
      subsequent samples. Unprocessed enamel includes 40 wt% calcium and self-scavenges
      oxygen, disrupting the isotopic measurements for the first half of a set and
      depleting subsequent organic standards by up to 9 per thousand. In sets without
      NBS 127 or calcium, such interference did not occur and an interlaboratory
      comparison of results from enamel shows reproducible, significantly correlated
      peaked delta18O patterns with a 2-3 per thousand dynamic range, consistent with
      previous results from contemporaneous teeth. Whereas both unprocessed enamel and
      the NBS 127 barium sulfate should be applied to biological phosphate
      ('biophosphate') stable isotope research with caution, seasonal variations in
      enamel phosphate delta18O are a paleoecologically valuable, reproducible
      phenomenon in theropod dinosaur teeth.

PMID- 15517531
TI  - Nitrogen balance and delta15N: why you're not what you eat during pregnancy.
AB  - Carbon (13C/12C) and nitrogen (15N/14N) stable isotope ratios were longitudinally
      measured in human hair that reflected the period from pre-conception to delivery
      in 10 pregnant women. There was no significant change in the delta13C results,
      but all subjects showed a decrease in delta15N values (-0.3 to -1.1 per thousand)
      during gestation. The mechanisms causing this decrease in hair delta15N have not
      been fully elucidated. However, since the delta15N values of dietary nitrogen and
      urea nitrogen are significantly lower compared to maternal tissues, it is
      hypothesized that the increased utilization of dietary and urea nitrogen for
      tissue synthesis during pregnancy resulted in a reduction of the steady state
      diet to a body trophic level effect by approximately 0.5-1 per thousand. An
      inverse correlation (R2 = 0.67) between hair delta15N and weight gain was also
      found, suggesting that positive nitrogen balance results in a reduction of
      delta15N values independent of diet. These results indicate that delta15N
      measurements have the ability to monitor not only dietary inputs, but also the
      nitrogen balance of an organism. A potential application of this technique is the
      detection of fertility patterns in modern and ancient species that have tissues
      that linearly record stable isotope ratios through time.

PMID- 15517532
TI  - Self-medication among Finnish young men in the beginning of common military
      service.
AB  - PURPOSE: Little is known about self-medication in adolescent and young adult
      males, particularly in ones exposed to increased stress. The objective of this
      article is to analyze self-medication and its predictors in young Finnish men at
      entry into common military service. METHODS: The responding men (n = 857) from
      nine brigades anonymously completed a self-administered questionnaire during the
      first conscription days before active military training in July 1999. The effect
      of pre-disposing, need and health behavior variables on self-medication was
      assessed using Andersen et al. theoretical health care utilization model.
      RESULTS: In the 2 weeks preceding the survey, 65% of the men reported self
      medication. Self-medication for pain or common cold symptoms was reported by 54%
      while 8% had taken caffeine tablets or other stimulants. Multivariate analysis on
      overall self-medication showed an association with brigade and using health
      services before the conscription. Along with pre-disposing variables, need
      variables were associated with self-medication for pain or common cold symptoms
      and self-medication with stimulants. Stimulant use was also associated with
      health behaviors such as trial with illegal drugs during lifetime. CONCLUSIONS:
      Young men frequently self-medicate at the initial stage of conscription that may
      pose them at an increased risk for adverse effects of medicines or other medical
      problems. The military and civilian primary health care providers should discuss
      the proper use of self-medication with young men.

PMID- 15517534
TI  - Tell the truth about spina bifida.

PMID- 15517533
TI  - Adverse reactions of Topiramate and Lamotrigine in children.
AB  - PURPOSE: To review the adverse drug reactions (ADRs) of Topiramate and
      Lamotrigine among children in Israel, and to compare the two drugs, based on
      their side effect profile and tolerability among this population. METHODS: We
      performed a cross-sectional study. Four paediatric neurologists from three
      different tertiary medical centres in Israel documented all cases of children
      from birth to the age 18 years, treated with Topiramate and/or Lamotrigine in
      their respective outpatient clinics and hospital wards. All present ADRs and
      their characteristics were recorded. RESULTS: Reports on 45 and 65 children
      treated with Topiramate and Lamotrigine respectively, were received. Half of the
      children treated with Topiramate suffered from one or more ADRs, as opposed to
      one-third of the children treated with Lamotrigine (p = 0.03). Most reactions
      were considered mild to moderate. There were no deaths or hospitalisations, but
      the drug had to be discontinued in about 10% of the patients due to ADRs. Most
      Topiramate and Lamotrigine ADRs appeared early in the treatment and were more
      frequent when Topiramate was an add-on versus a monotherapy drug. Most ADRs of
      both Topiramate and Lamotrigine were related to the central nervous system; while
      poor appetite, drowsiness, speech difficulties and weight loss were observed only
      with Topiramate, and rash and headaches only with Lamotrigine. Nervousness and
      seizure aggravation were more frequent ADRs of Topiramate whereas sleep
      disturbances were observed more in children treated with Lamotrigine. CONCLUSION:
      Results of this study indicate that Lamotrigine causes ADRs less frequently than
      Topiramate; however both medications are generally well tolerated. Topiramate and
      Lamotrigine differ in their central nervous system side effect profile.

PMID- 15517535
TI  - What does an increased atrial-to-ventricular length ratio mean in fetuses with
      atrioventricular septal defect?

PMID- 15517536
TI  - Reference ranges for umbilical and middle cerebral artery pulsatility index and
      cerebroplacental ratio in prolonged pregnancies.
AB  - OBJECTIVE: To construct normal ranges for umbilical artery pulsatility index (UA
      PI), middle cerebral artery pulsatility index (MCA PI) and cerebroplacental ratio
      (CPR) in prolonged pregnancies according to strict methodological criteria using
      polynomial regression analysis. METHODS: This was a retrospective, cross
      sectional observational study involving 140 women, 10 women for each gestational
      day between 287 and 300 days of gestation. Fetal Doppler parameters were assessed
      to construct normal reference ranges for UA PI and MCA PI. CPR was calculated as
      a ratio of MCA PI/UA PI. RESULTS: Mathematical modeling of the data demonstrated
      that the optimal fit was a linear polynomial one. Mean, 5th and 95th centiles
      were calculated for UA, MCA and CPR and centile curves from the regression
      analysis were constructed. CONCLUSIONS: Reference ranges for UA PI, MCA PI and
      CPR in prolonged pregnancies have been constructed. MCA PI shows a wider range
      than previously reported in the literature.

PMID- 15517537
TI  - Three-dimensional power Doppler imaging of early-stage cervical cancer.
AB  - OBJECTIVES: To characterize intratumoral vascularization in early-stage cervical
      cancer by three-dimensional (3D) power Doppler ultrasound. METHODS: One hundred
      and forty-one patients with carcinoma of the uterine cervix and 30 normal
      controls were studied by transvaginal 3D power Doppler ultrasound. The tumor
      volume of the cervical cancer was determined. The blood flow within the tumor or
      normal cervix was measured and expressed as the vascularization index (VI), flow
      index (FI) and vascularization flow index (VFI). RESULTS: Of the 141 patients
      with cervical cancer, 44 patients had undergone prior cervical conization. Eighty
      seven patients had measurable cervical tumors, of whom five had had prior
      conization. Abundant intratumoral power Doppler signals could be detected, and
      the VI, FI and VFI were significantly elevated in cervical cancer patients
      compared with women with a normal cervix and patients in whom no cervical tumor
      could be detected (P < 0.05, one-way ANOVA). We observed four types of
      intratumoral vascularity patterns, which did not significantly differ in VI, FI
      and VFI: localized, peripheral, scattered and single-vessel types. Cervical tumor
      volume was positively correlated with FI (linear regression, r = 0.373, P =
      0.001), but not with VI or VFI. CONCLUSIONS: 3D power Doppler ultrasound provides
      a useful tool to investigate intratumoral vascularization and volume of cervical
      cancer.

PMID- 15517538
TI  - An anatomical fetal brain structure and a normal variant mimicking anomalies on
      routine neurosonographic imaging: report of two cases.
AB  - We present two cases in which an anatomical structure, the calcar avis, and a
      normal variant, a bifid choroid plexus, mimicked abnormalities on routine
      prenatal ultrasound examination. To the best of our knowledge these pitfalls have
      only been described in neonates. A familiarity with these false images is
      important to avoid erroneous diagnoses.

PMID- 15517539
TI  - The role of color and power Doppler ultrasound in the prenatal diagnosis of
      sirenomelia.
AB  - Sirenomelia is a rare congenital abnormality characterized by a variety of
      anomalies involving the lower limbs, severe oligohydramnios, bilateral renal
      agenesis, anorectal atresia and aberrant fetal vasculature. The prenatal
      diagnosis and differentiation from isolated bilateral renal agenesis is severely
      limited by the accompanying oligohydramnios that hinders visualization of fetal
      anatomy. We present three prospectively assessed cases of sirenomelia, two of
      which had bilateral renal agenesis, and all of which had a single umbilical
      artery derived from the aberrant vasculature that accompanies the syndrome.

PMID- 15517540
TI  - An advanced double column-switching technique (LC-LC) for liquid
      chromatography/electrospray ionisation tandem mass spectrometry for fully
      automated analysis of caspofungin.
AB  - Caspofungin (MK-0991; L-743,872) is the first representative of a new important
      class of antifungal agents, the glucan synthesis inhibitors. To the authors' best
      knowledge, to date only one high-performance liquid chromatography (HPLC) method
      has been published for the determination of caspofungin in serum. Severe
      difficulties with sorption were described. We developed a new method which
      addresses these difficulties using an advanced column-switching technique for
      fully automated analysis of caspofungin in serum without any pre-treatment.
      Extraction was performed automatically inline, using a diol column, followed by
      chromatography on a CN column. Detection was performed by electrospray ionisation
      tandem mass spectrometry (ESI-MS/MS) with isolation and fragmentation in the
      positive ion mode. Total analysis time was 30 min. Detection of caspofungin was
      achieved by retention time, isolation and fragmentation of the double positively
      charged caspofungin ion. This LC/MS assay was validated for between-run accuracy
      (max. 110%) and precision (max. CV 16.1%). The lower limit of quantification was
      0.2 microg/mL. The analytical method with fully automated inline extraction of
      caspofungin described here removes the need for difficult and time-consuming
      sample pre-treatment. Sorption of caspofungin is not of importance. Additional
      advantages of the new method are that only a small quantity of serum (5 microL)
      is needed and that the method is very specific.

PMID- 15517541
TI  - Expression of human apolipoprotein(a) kringles in colon cancer cells suppresses
      angiogenesis-dependent tumor growth and peritoneal dissemination.
AB  - BACKGROUND: Anti-angiogenesis therapy has been regarded as a promising treatment
      of cancer based on the fact that most tumors and their metastasis are
      angiogenesis-dependent. Gene therapy can potentially expand the horizons of tumor
      angiogenesis therapy by virtue of its ability to produce high concentrations of
      therapeutic agents in a local area for a sustained period. The present study was
      performed to evaluate the therapeutic potential of gene therapy for the treatment
      of cancer and metastasis. METHODS: The murine colon carcinoma cell line CT26 was
      manipulated ex vivo to express an anti-angiogenic molecule, LK68, consisting of
      human apolipoprotein(a) kringle domains, KIV(9)-KIV(10)-KV, using retrovirus
      mediated gene transfer. Its effects on colon tumor growth and metastasis were
      evaluated in experimental animal models established by injecting LK68-expressing
      and control CT26 cells subcutaneously or into the peritoneal cavity of BALB/c
      mice, respectively. RESULTS: Expression of LK68 significantly suppressed colon
      tumor growth in mice, but did not influence the growth of tumor cells in vitro.
      Immunohistochemical analysis of tumor tissues revealed a significant reduction in
      microvessel density in LK68-expressing tumors. Thus, the suppression of tumor
      growth appears to result mainly from inhibition of tumor angiogenesis. This
      decrease in vessel density is correlated with a notable increase in tumor cell
      apoptosis in vivo, but has no influence on proliferation. Moreover, expression of
      LK68 prevents peritoneal dissemination, and consequently improves overall host
      survival. CONCLUSIONS: These results collectively indicate that a gene therapy
      strategy using LK68 cDNA is useful for the treatment for both colon tumor growth
      and peritoneal dissemination.

PMID- 15517542
TI  - Pharmacovigilance-related topics at the level of the International Conference on
      Harmonisation (ICH).
AB  - Marketing authorisations for medicines need to be based on the universal criteria
      quality, safety and efficacy, whilst taking into account local public health
      needs. With view to using resources efficiently and avoiding delay in access to
      medicines, scientific standards for investigating quality, safety and efficacy
      should be universal too. A major step to achieve this was taken in 1990 when the
      International Conference on Harmonisation of Technical Requirements for
      Registration of Pharmaceuticals for Human Use (ICH) was established between
      authorities and industry in the European Union (EU), Japan and the United States.
      Since then more than 50 ICH Guidelines have been published, out of which six are
      specific to pharmacovigilance. They refer to management and expedited reporting
      of individual adverse drug reaction (ADR) cases, including electronic formats,
      periodic reporting of worldwide data and planning of pharmacovigilance. Their
      development has to be seen in the context of initiatives taken in the three ICH
      Regions to strengthen pharmacovigilance. Most recently this involves making use
      of risk management concepts, reflecting new thinking of proactivity in
      pharmacovigilance. Moreover, consideration is given to regional and international
      cooperation beyond the ICH Regions.

PMID- 15517544
TI  - Gene transfer into skeletal muscle using novel AAV serotypes.
AB  - BACKGROUND: Skeletal muscle is an interesting target for gene delivery because of
      its mass and because the vectors can be delivered in a noninvasive way. Adeno
      associated virus (AAV) vectors are capable of transducing skeletal muscle fibers
      and achieving stable and safe transgene expression. To date, most animal
      experiments using AAV have been based on AAV serotype 2, but some recent studies
      have demonstrated that AAV1 is more efficient than AAV2/2 in transducing muscle
      fibers. Recently, novel AAVs (AAV7 and AAV8) were isolated from rhesus macaques.
      METHODS: We injected three different muscles (gastrocnemius, soleus, biceps
      femoris) of immunocompetent C57BL/6 mice with different pseudotyped AAV serotypes
      (AAV2/1, AAV2/2, AAV2/5, AAV2/7 and AAV2/8) and quantitatively compared the
      different gene transfer efficiencies. RESULTS: The efficiencies of transduction
      in skeletal muscle with AAV2/7 and AAV2/8 were similar to AAV2/1, and higher than
      that seen with AAV2/2 and AAV2/5. All serotypes were able to transduce both slow
      and fast muscle fibers similarly at the vector titer used (1x10(11) genome copies
      per mouse). Despite a limited inflammatory response (slightly higher when using
      AAV2/2, AAV2/7 and AAV2/8 vectors than AAV2/1 and AAV2/5), transgene expression
      was observed throughout the length of the experiment. DISCUSSION: These results
      show that AAV2/7 and AAV2/8 are able to transduce muscle fibers of
      immunocompetent mice very efficiently, offering new perspectives in gene transfer
      of skeletal muscle.

PMID- 15517543
TI  - Physician speciality and adherence to guidelines for the treatment of
      unsubstantiated uncomplicated urinary tract infection among women.
AB  - PURPOSE: To evaluate the variance in rates of physician adherence to guidelines
      for the empiric treatment of uncomplicated urinary tract infection (UTI) in women
      recommending either trimethoprim-sulfamethoxazole (TMP-SMX) or nitrofurantoin, in
      all relevant physician subspecialities practising in a managed care community
      setting in Israel. METHODS: Data were derived from the computerised medical
      records of Maccabi Healthcare Services, a health maintenance organisation (HMO)
      in Israel providing care to more than 1.6 million members nation-wide. The study
      population included women aged 18-75 years without risk factors for complicated
      UTI who were treated empirically with antibiotics for a diagnosis of acute
      cystitis or UTI. The data set consisted of 64,236 initial physician-patient
      encounters from July 2000 to June 2002. Physician adherence to guidelines was
      calculated by comparing the proportion of cases treated with each individual
      drug. A binary regression model was used to evaluate factors associated with
      suboptimal adherence to the guidelines. RESULTS: Nitrofurantoin was the most
      frequently prescribed drug (18.51%), followed by TMP-SMX (17.04%) for a crude
      rate of adherence of 35.6%. Adherence was observed to be highest in cases treated
      by urologists (OR=2.8, 95%CI: 2.4, 3.3), followed by gynaecologists (OR=1.9,
      95%CI: 1.7, 2.31), with family practice as the referent speciality. The medical
      school attended was also found to be significant. CONCLUSIONS: Physician
      speciality was found to be significantly associated with rate of adherence to
      guidelines, with higher rates being observed amongst specialities such as
      urologists who presumably have greater familiarity with the subject matter.

PMID- 15517545
TI  - Use of the nuclease inhibitor aurintricarboxylic acid (ATA) for improved non
      viral intratumoral in vivo gene transfer by jet-injection.
AB  - BACKGROUND: Stability, integrity and retention of the DNA within the targeted
      tissue is decisive for efficient gene transfer using naked DNA. Pre-clinical and
      clinical studies require reproducible transfection rates by preventing rapid
      degradation of naked DNA in the transduced tissue. Tumor tissues contain nuclease
      activity, which can affect DNA stability if naked DNA is used. Therefore,
      inhibition of nuclease-mediated DNA degradation by the nuclease inhibitor
      aurintricarboxylic acid (ATA) might lead to improved gene transfer efficiency in
      tumor tissues. METHODS: For both, DNA-degradation analysis and in vivo gene
      transfer experiments, the beta-galactosidase (LacZ)-expressing pCMVbeta and the
      cytosine deaminase (CD)-expressing pCMV-CD plasmid were used. Influence of the
      nuclease inhibitor ATA was determined in tumors, in which naked pCMVbeta or pCMV
      CD DNA and ATA was co-administered by jet-injection. The nuclease activity and
      inhibition by ATA was analyzed using the DNase Alert detection system. The
      influence of ATA on LacZ expression was determined by specific ELISA and its
      effect on the therapeutic efficacy of CD gene transfer on tumor growth was
      determined in vivo. RESULTS: The screening of different human mammary and colon
      carcinoma models revealed strong nuclease activity rapidly degrading naked
      plasmid DNA. Co-administration of ATA with pCMVbeta or pCMV-CD for in vivo jet
      injection of tumors prevented DNA from nuclease degradation associated with
      either increased LacZ gene expression or improved reduction in tumor growth.
      CONCLUSIONS: Tumor-associated nuclease activity is a notable hurdle in gene
      transfer of naked DNA and therefore inhibition of nucleolytic degradation of
      plasmid DNA facilitates intratumoral gene expression.

PMID- 15517546
TI  - Increased cardiac atrial-to-ventricular length ratio in the fetal four-chamber
      view: a new marker for atrioventricular septal defects.
AB  - OBJECTIVES: Atrioventricular septal defects (AVSDs) are the most common cardiac
      abnormality in fetuses with numerical chromosomal aberrations, in particular
      trisomy 21. The majority of AVSDs are not detected by routine ultrasound
      examination in pregnancy. We report two simple cardiac measurements that may
      substantially improve antenatal detection of AVSDs. METHODS: Cross-sectional
      ultrasound images through the fetal thorax demonstrating the four-chamber plane
      of the heart were obtained in 123 normal fetuses between 10 and 38 weeks of
      gestation. Heart length was measured at the level of interventricular septum by
      placing the calipers on the epicardium at the apex of the heart and on the
      endocardium at the top of the atrium. Ventricular length was measured by shifting
      the atrial caliper to the crossing point of the ventricular septum and mitral
      valve. Atrial length was calculated as the difference between the heart length
      and ventricular length. Based on these measurements, the atrial-to-ventricular
      length (AVL) ratio was calculated. Data were compared to measurements from 29
      consecutive fetuses with AVSD between 13 and 39 weeks of gestation. RESULTS: In
      normal fetuses, the AVL ratio did not change with gestation and the mean AVL
      ratio was 0.47 (95% prediction interval 0.35 to 0.63). In the AVSD group, the
      mean AVL ratio was 0.77 (range, 0.59-0.99). If a cut-off value for the AVL ratio
      of 0.6 was chosen, the detection rate of AVSD was 86.2% at a 5.7% false-positive
      rate. For a 100% detection rate, the false-positive rate was 7.3%. CONCLUSIONS:
      The AVL ratio can accurately discriminate between hearts with AVSDs and normal
      cardiac anatomy. Incorporation of the AVL ratio measurement into routine
      antenatal ultrasonography may substantially improve the ability to diagnose AVSDs
      antenatally.

PMID- 15517547
TI  - Prenatal diagnosis of Shone's syndrome: parental counseling and clinical outcome.
AB  - OBJECTIVE: To describe a series of fetuses diagnosed as having Shone's syndrome,
      which includes four cardiac defects and for which there is a wide variety of
      clinical presentations, surgical treatments and outcomes, and to discuss the
      counseling strategy. METHODS: We reviewed retrospectively the records of four
      babies who were suspected prenatally to have Shone's syndrome. RESULTS: The mean
      age at diagnosis was 27.5 (range, 22-35) weeks. A small left ventricle, mitral
      and aortic annulus and ascending aorta were detected in three cases. In three
      fetuses there was an abnormal mitral valve apparatus and in two fetuses a sub
      aortic membrane was detected. Coarctation of the aorta was an impending diagnosis
      in three babies. Following counseling, all parents decided to continue the
      pregnancy to term. Echocardiographic evaluation was performed soon after birth.
      The mean mitral valve annulus diameter was 8.2 (range, 7-10) mm, and that of the
      aortic valve annulus was 6 (range, 5-7) mm. The aortic valve was bicuspid in all
      babies with an additional sub-aortic membrane in two babies. Doppler ultrasound
      examination revealed high-velocity flow through the mitral valve in three babies;
      two of them had a parachute mitral valve. Coarctation repair was performed in two
      babies during the first week of life. One patient underwent mitral valvuloplasty
      followed by later mitral valve replacement. All patients were alive after a mean
      of 7.8 (range, 3.3-10.5) years' follow-up. CONCLUSION: When counseling families
      regarding fetal Shone's syndrome, it is important to emphasize the wide variety
      of clinical presentations and possible outcomes. Differentiation between
      hypoplastic left ventricle and Shone's complex is crucial and may influence the
      physician's attitude, the presentation of the case to the family and the family's
      final decision.

PMID- 15517548
TI  - Fetal head biometry following in-utero repair of myelomeningocele.
AB  - OBJECTIVE: To evaluate the impact of prenatal myelomeningocele repair on fetal
      head biometry. METHODS: Fifty fetuses underwent open fetal myelomeningocele
      repair at our institution between January 1998 and July 2002. All had serial head
      circumference (HC) and lateral ventricular diameter (VD) measurements taken
      preoperatively and weekly for 8 weeks after repair. Cortical index (CI) was
      defined as HC/VD. Measurements were compared with gestational age-matched values
      from nomograms. One-sample t-test, ANOVA and repeated measures analysis were used
      to assess HC, VD and CI after fetal repair. RESULTS: Preoperatively, the HC in
      fetuses with myelomeningocele was smaller than control values (186.4 vs. 198.8
      mm, P = 0.0004). Eight weeks' postoperatively this difference had resolved (293
      vs. 301.6 mm, P = 0.76). The mean increase in CI after repair was 20% (P = 0.02)
      compared with the predicted 51% in normal cases. The average increase in VD was
      3.9 mm (38.8%, P < 0.001). CONCLUSIONS: Mid-gestational repair of
      myelomeningocele alters fetal head growth. Increased CI suggests HC changes are
      not due to ventriculomegaly alone.

PMID- 15517549
TI  - Upper level of the spina bifida defect: how good are we?
AB  - OBJECTIVE: To assess the accuracy of obstetric sonography in determining the
      upper level of myelomeningocele lesions. METHODS: This was a retrospective study
      of 171 consecutive cases of spina bifida repaired in utero. The upper level of
      the lesion as determined by obstetric sonography was assigned by community
      physicians prior to referral in the second trimester and by the authors at
      Vanderbilt University Medical Center during preoperative evaluation. One hundred
      and eleven cases had levels established by plane-film X-ray or magnetic resonance
      imaging after delivery and this was regarded as the gold standard. RESULTS: Of
      the 171 community examinations, only 29% identified a specific upper level of the
      lesion; our corresponding examinations specified the lesion level in all cases.
      Of the 111 cases that had upper levels of the lesion established by post-delivery
      imaging, corresponding levels were available for comparison from 35 of the
      community examinations and from 111 of the examinations performed at Vanderbilt.
      All three assigned levels were available for comparison in 35 cases. In 26% of
      cases, community-assigned levels agreed exactly with post-delivery levels, while
      66% agreed within one level and 80% agreed within two levels. In 38% of cases,
      levels assigned at Vanderbilt agreed exactly with post-delivery levels, while 78%
      agreed within one level and 96% agreed within two levels. Upper levels of the
      lesion assigned at Vanderbilt were significantly more accurate overall compared
      with those assigned by community physicians (signed rank test [paired
      comparison], P = 0.048). However, comparison of lesion levels assigned at
      Vanderbilt in the first 50 vs. the last 61 cases revealed a significant learning
      effect (Fisher's exact test, P = 0.03). When comparison of lesion levels assigned
      by community physicians was restricted to the first 50 cases at Vanderbilt,
      accuracy was similar (n = 13; t-test, P = 0.16; rank sum test, 0.31).
      CONCLUSIONS: Community physicians were successful in assigning the upper level of
      the spina bifida lesion only 29% of the time. When successful, the accuracy of
      these determinations was similar to that of the authors at Vanderbilt. A
      significant learning effect was demonstrated by improved accuracy over time at
      Vanderbilt. A concerted continuing medical education effort is indicated to
      improve the imaging skills of physicians in the accurate diagnosis of the
      severity of spina bifida in fetuses.

PMID- 15517550
TI  - The utility of mixed-effects covariate analysis in rapid selection of doses in
      pediatric subjects: a case study with fexofenadine hydrochloride.
AB  - Fexofenadine hydrochloride is a non-sedating antihistamine that is used in the
      treatment of symptoms associated with seasonal allergic rhinitis and chronic
      idiopathic urticaria. A pooled analysis of pharmacokinetic data from children 6
      months to 12 years of age and adults was conducted to identify the dose(s) in
      children that produce exposures comparable to those in adults for the treatment
      of seasonal allergic rhinitis. The pharmacokinetic parameter database included
      peak and overall exposure data from 269 treatment exposures from 136 adult
      subjects, and 90 treatment exposures from 77 pediatric allergic rhinitis
      patients. The data were pooled and analysed using NONMEM software, version 5.0. A
      covariate model based on body weight and age and a power function model based on
      body weight were identified as appropriate models to describe the variability in
      fexofenadine oral clearance and peak concentration, respectively. Individual oral
      clearance estimates were on average 44%, 36% and 61% lower in children 6 to 12
      years (n=14), 2 to 5 years (n=21), and 6 months to 2 years (n=42), respectively,
      compared with adults. Trial simulations (n=100) were carried out based on the
      final pharmacostatistical models and parameter estimates to identify the
      appropriate dose(s) in children relative to the marketed dose of 60 mg
      fexofenadine hydrochloride in adults. The trials were designed as crossover
      studies in 18 subjects comprising various potential dosing regimens with and
      without weight stratification. Pharmacokinetic parameter variability was assumed
      to have a log-normal distribution. Individual weights and ages were simulated
      using mean (SD) estimates derived from the studies used in this analysis and
      proportional measurement/model mis-specification errors derived from the analysis
      were incorporated into the simulation. The results indicated that a 30 mg dose of
      fexofenadine hydrochloride administered to children 1 to 12 years of age and
      weighing >10.5 kg and a 15 mg dose administered to children 6 months and older
      and weighing <or=10.5 kg produces exposures similar to those seen with the 60 mg
      dose in adults.

PMID- 15517551
TI  - Portal and umbilical venous blood supply to the liver in the human fetus near
      term.
AB  - OBJECTIVES: To determine the contribution of the umbilical (UV) and portal (PV)
      veins to blood supply to the human fetal liver in a low-risk population near
      term, and to assess the distribution between the left and right lobes. METHODS:
      In 91 low-risk pregnancies with normally grown fetuses at 36 weeks of gestation
      we measured the distribution of blood in the UV and PV to the right and left
      hepatic lobes using ultrasound imaging and Doppler techniques. RESULTS: The
      median (10(th), 90(th) centile) total UV return was 205 (127, 294) mL/min, of
      which 25% (13, 47%) was shunted through the ductus venosus, 55% (35, 66%) was
      distributed to the left hepatic lobe, and 20% (11, 30%) was distributed to the
      right hepatic lobe. While the left lobe was supplied exclusively by the UV, the
      right lobe received 50% (20, 70%; 37 (16, 65) mL/min) of its venous blood supply
      from the PV. The total venous blood supply to the liver parenchyma was 185 (114,
      277) mL/min; 21% (8, 34%) came from the PV supply to the right lobe and the
      remainder came from the UV supply to both lobes. CONCLUSIONS: The venous supply
      to the left lobe is from nutrient-rich UV blood; for the right lobe, half is from
      UV blood and half from nutrient-poor PV blood. This watershed between the portal
      and umbilical venous flows to the fetal liver suggests a corresponding functional
      dichotomy; this may be modified by hemodynamic influences, with long-term
      consequences.

PMID- 15517552
TI  - Metabolomic analysis of saponins in crude extracts of Quillaja saponaria by
      liquid chromatography/mass spectrometry for product authentication.
AB  - Analysis of 50% aqueous methanolic extracts of bark of Quillaja saponaria Molina
      (quillaja) by liquid chromatography/mass spectrometry (LC/MS), using negative ion
      electrospray, revealed over 100 saponins. The majority could be assigned to known
      structures or generalised variations of these from the product ion spectra
      obtained by serial mass spectrometry in a quadrupole ion trap mass spectrometer.
      Ten saponins contained a fatty acid domain terminated with both a pentose and
      deoxyhexose unit, a feature thus far only reported in QS-III. Twenty saponins
      were based on a hydroxylated derivative of quillaic acid, whereas only six 22beta
      hydroxyquillaic acid saponins have been described. The occurrence of pairs of
      saponins differing only by the presence of a rhamnose or xylose unit in the C-3
      substituted saccharide was readily observed in two-dimensional mass maps, and
      these showed the presence of the unreported 'rhamnose partner' of QS-III.
      However, one sample labelled as Q. saponaria appeared to lack all saponins
      containing rhamnose in the C-3 saccharide. Methods to authenticate saponin
      extracts of quillaja by LC/MS are suggested based on the general metabolomic
      profile, the occurrence of specific major saponins covering known structural
      variations, or the presence of saponins containing the unusual fatty acid domain,
      revealed by neutral loss analysis.

PMID- 15517553
TI  - The mouse chorionic gonadotropin beta-subunit-like (muCG beta l) molecule
      produced by tumor cells elicits the switch of T-cell immunity response from TH2
      to TH1 in mice immunized with DNA vaccine based on rhesus monkey homologous CG
      beta (rmCG beta).
AB  - BACKGROUND: CG beta is expressed not only in placenta, but also in a wide range
      of tumors. To study DNA vaccine based on xenogeneic CG beta for cancer immuno
      therapy, we investigated whether rhesus monkey CG beta (rmCG beta) DNA vaccine
      could induce protective T-cell responses and humoral responses in mouse. METHODS:
      We constructed a plasmid containing the rmCG beta coding sequence. Two cloned
      syngeneic SP2/0 myeloma cell lines that stably express muCG beta l (SP2/0-muCG
      beta l) and HN (SP2/0-HN) protein were established. Inoculation of these cell
      lines was made into mice that had been immunized with DNA vaccine. Specific IgG
      and IgG type were measured by ELISA and the cytokine expression was detected with
      RT-PCR. To measure the lymphocyte metabolic activity, the MTS assay was used.
      RESULTS: After injection of SP2/0-muCG beta l into mice that had been immunized
      with DNA vaccine, a significant increase in the IgG2a specific to the antigen (p
      < 0.05) and a decrease in the specific IgG1 (p < 0.05) were measured. The
      expression of T(H)1 but not T(H)2 cytokines, including IFN-gamma and IL-2, were
      detected in the splenocytes. However, injection of tumor cells expressing
      irrelevant or mock molecules into immunized mice could not induce these changes.
      The survival rate of vaccine-immunized mice injected with SP2/0-muCG beta l was
      as high as 58.3% after 55 days. CONCLUSIONS: The rmCG beta DNA vaccine has proved
      to be a potential strategy for protection against tumors with homologous
      molecules. The muCG beta l produced by tumors is able to elicit an immunity
      switch from T(H)2 to T(H)1 in vaccinated mice.

PMID- 15517555
TI  - Reduction of organic dyes in matrix-assisted laser desorption/ionization and
      desorption/ionization on porous silicon.
AB  - Reduction of analytes in matrix-assisted laser desorption/ionization (MALDI)
      often obscures the actual determination of molecular structure. To address the
      redox reactions in laser desorption/ionization processes, the organic dyes
      Methylene Blue, Janus Green B, Crystal Violet and Rhodamine B were analyzed by
      MALDI or by desorption/ionization on porous silicon (DIOS). Susceptibility to
      reduction in MALDI was dependent on both the reduction potentials of analytes and
      the molar ratio of analyte to matrix molecules. Addition of Cu(II) ions as an
      electron scavenger suppressed the reduction of Methylene Blue in MALDI. The
      results suggested that electron transfer to analytes from the sample target
      and/or from the matrix contributed to the reduction. In DIOS, the reductions of
      organic dyes were more prominent than in MALDI, and were not prevented by Cu(II)
      ion doping, probably due to direct contact of the analytes with silicon which had
      little electric resistance.

PMID- 15517556
TI  - Economic evaluation of ultrasound screening options for structural fetal
      malformations.
AB  - OBJECTIVE: To perform a cost-effectiveness analysis comparing the current Italian
      situation of no organized screening program for structural fetal malformations
      with an organized screening model involving a scan at 19-21 weeks of gestation.
      METHODS: Assumptions were made about the number of pregnant women examined per
      year, the number of ultrasound examinations (screening and diagnostic) and
      amniocenteses, the prevalence of fetal anomalies, ultrasound sensitivity and
      specificity and the rates of termination of pregnancy and of fetal death. The
      costs included procedures performed during and after the diagnosis of
      malformations, and the resources required to organize the program. Data sources
      were a literature review, estimates and national tariffs. A sensitivity analysis
      considered variations in screening test sensitivity, number of private scans and
      costs of ultrasound, fetal echocardiography, amniocentesis, care for malformed
      infants and organization. RESULTS: An organized program would increase the number
      of diagnosed malformations (+10.7%) and decrease the number of malformed infants
      (-19.9%). It would also decrease the total cost of screening, from 505 billion to
      400 billion euros (-20.7%), decrease the cost per woman examined from 971 to 770
      euros (-20.7%) and decrease the cost per malformed fetus diagnosed from 79,085 to
      56,637 euros (-28.4%). CONCLUSIONS: In all scenarios considered, an organized
      program would lead to increased detection of malformations at lower cost. Further
      cost analyses should provide a better representation of resources used,
      especially those related to the care of malformed infants, while cost-benefit
      assessments should include all the consequences of prenatal diagnosis, such as
      those deriving from false results and those for both the woman and society,
      including ethical issues.

PMID- 15517554
TI  - Fragmentation study of short-chain products derived from oxidation of
      diacylphosphatidylcholines by electrospray tandem mass spectrometry:
      identification of novel short-chain products.
AB  - Lineloyl-palmitoyl (PLPC) and arachidonoyl-palmitoyl (PAPC) phosphatidylcholine
      were oxidized under Fenton reaction conditions (H2O2 and Fe2+), and the short
      chain products formed were identified by electrospray ionization mass
      spectrometry (ESI-MS). The short-chain products resulted from beta-cleavage of
      oxygen-centered radicals and comprised aldehydes, hydroxyaldehydes and
      dicarboxylic acids that yielded both [MH]+ and [MNa]+ ions. The fragmentation of
      the [MH]+ and [MNa]+ ions of the peroxidation products was studied by tandem mass
      spectrometry (MS/MS). The MS/MS spectra of both ions showed ions resulting from
      characteristic losses of glycerophosphatidylcholine. Other product ions,
      resulting from C-C cleavages occurring in the vicinity of the functional group,
      and fragmentations involving the hydroxy groups, were the most informative since
      they allowed us to obtain structural information relating to the sn-2 acyl
      residue. Both fragmentation pathways are due to charge-remote fragmentation
      occurring by a 1,4-hydrogen elimination mechanism and/or by homolytic cleavage.
      Furthermore, the fragmentation pathway of some ions observed in the ESI-MS
      spectrum was not consistent with the fragmentation behavior expected for some of
      the short-chain species identified in the literature and allowed the reassignment
      of the ions as different structures. Isobaric ions were observed in the ESI-MS
      spectra of both oxidized phospholipids, and were differentiated based on distinct
      fragmentation. The detailed knowledge of lipid peroxidation degradation products
      is of major importance and should be very valuable in providing new markers for
      oxidative stress signaling and for disease states monitoring.

PMID- 15517557
TI  - Early sonographic detection of recurrent fetal eye anomalies.
AB  - OBJECTIVE: To determine the possible association between congenital eye anomaly
      of a previous child in the family and current congenital eye anomaly. METHODS: An
      early transvaginal anomaly scan at 14-16 gestational weeks was used to diagnose
      fetal eye anomalies in five cases in which at least one previous child in the
      family had the same congenital eye anomaly. RESULTS: At least one cataract was
      detected in four of the five fetuses and bilateral anophthalmia in one. The
      congenital cataract in one case was part of multiple pterygium syndrome. Both of
      these extremely rare malformations are commonly associated with other fetal
      anomalies. CONCLUSION: Our data suggest that a detailed targeted ultrasound
      survey with a special focus on the orbital region should be offered at the time
      of genetic counseling to couples with children with congenital eye anomalies.

PMID- 15517560
TI  - Production of precise microbiology standards using flow cytometry and freeze
      drying.
AB  - BACKGROUND: Quality control standards provide a quantity of microorganisms for
      routine use in microbiology to demonstrate the efficacy of testing methods and
      culture media. Standards are normally prepared by diluting a culture of
      microorganisms to obtain a suspension that contains an estimated number of colony
      forming units per milliliter. The variability and inaccuracy of these standards
      increase the potential for false results. Flow cytometry has been used
      extensively to prepare precise standards of Cryptosporidium and Giardia that
      contain exact numbers of organisms in a volume of liquid (1). However, the same
      levels of accuracy have yet to be obtained for bacterial quality control
      standards. METHODS: A modification of a Becton Dickinson FACScalibur flow
      cytometer enabled 30 bacterial cells to be sorted into a single droplet, mixed
      with a cryoprotective solution within the droplet, and frozen in liquid nitrogen.
      The frozen droplets were then freeze dried for stable preservation of the viable
      bacterial cells. RESULTS: A freeze-dried sphere 3 mm in diameter was produced,
      which contained 30 microorganisms. The within-batch variation for these freeze
      dried spheres was no greater than two standard deviations, and the between-batch
      variation was less than one standard deviation. CONCLUSIONS: Bacterial reference
      controls can now be produced with consistent accuracy and unparalleled precision,
      thus enabling harmonization across the microbiological testing industry.

PMID- 15517561
TI  - Effects of the histone deacetylase inhibitor trichostatin A on nuclear texture
      and c-jun gene expression in drug-sensitive and drug-resistant human H69 lung
      carcinoma cells.
AB  - BACKGROUND: Texture analysis of chromatin patterns by image cytometry can be used
      in the development and refinement of diagnosis and prognosis of cancers and in
      the follow-up of therapies. However, little is known about the biological
      mechanisms underlying these patterns. Epigenetic mechanisms as histone
      posttranslational modifications and particularly histone acetylation could play a
      major role in the determination of these chromatin patterns and then influence
      nuclear texture measurements. METHODS: This study examined the consequences of
      treatment by the histone deacetylase inhibitor trichostatin A (TSA) on the
      nuclear texture in human cell lines sensitive and resistant to chemotherapy.
      Small cell lung carcinoma H69 cells and their variant H69-VP, which is resistant
      to etoposide, were incubated with 100 ng/ml of TSA for 0 to 24 h. Nuclear texture
      was evaluated by image cytometry and compared with the histone H4 acetylation
      level measured by western blotting and expression of c-jun gene evaluated by
      reverse transcription and real-time polymerase chain reaction. RESULTS: TSA
      treatment induced an increase in histone H4 acetylation level in both cell lines.
      However, at the level of chromatin texture, sensitive H69 cells displayed a
      progressive chromatin decondensation up to 24 h, whereas resistant H69-VP showed
      rapid (8 h) but transient changes. Similarly, expression of c-jun increased
      regularly in TSA-treated H69 cells. In H69-VP cells, an increase was also
      observed up to 12 h followed by a decrease after 24 h of treatment. CONCLUSIONS:
      Analysis of nuclear texture appeared to be a sensitive technique to detect
      chromatin pattern alterations induced by the histone deacetylase inhibitor TSA in
      the H69 cell line and enabled the observation of chromatin pattern discrepancies
      between chemotherapeutic drug-sensitive and drug-resistant cells during this
      treatment. When c-jun gene expression was analyzed as gene sensitive to
      epigenetic control, these textural differences seemed to be correlated to gene
      expression.

PMID- 15517563
TI  - Flow cytometry-based approach to ABCG2 function suggests that the transporter
      differentially handles the influx and efflux of drugs.
AB  - BACKGROUND: To better characterize the function of the ABCG2 transporter in
      vitro, we generated three cell lines (MXRA, MXRG, and MXRT) stably expressing
      ABCG2 after transfection of wild-type ABCG2 and two mutants (R482G and R482T),
      respectively. METHODS: ABCG2 expression and function were analyzed by flow
      cytometry using monoclonal antibodies, a variety of fluorescent substrates, and a
      series of potential inhibitors of the transporter. RESULTS: ABCG2 expression was
      detected in all cell lines. The cell lines effluxed mitoxantrone (MXR), but only
      the mutants effluxed rhodamine 123 (Rho123), SYTO13, doxorubicin, and
      daunorubicin. After incubation with MXR, intracellular accumulations were 9- and
      22-fold higher in MXRA than in MXRT and MXRG cells, respectively, suggesting that
      ABCG2 also modulates the influx rate of the drug. Flow cytometry kinetic studies
      of MXR efflux showed that MXRG cells effluxed 50% of the drug at a faster rate
      than MXRA and MXRT cells (t50: 15.3 min vs. 27.8 and 44.5 min, respectively).
      MXRG cells also extruded Rho123 and SYTO13 at a faster rate than MXRT cells.
      ABCG2-mediated transport was inhibited by fumitremorgin C, cyclosporine A, and
      PSC-833, but not by verapamil or probenecid. MXRG cells displayed the highest
      level of resistance to MXR, doxorubicin, and daunorubicin in the cytotoxicity
      assays. CONCLUSIONS: Glycine mutations at position 482 have a significant impact
      on ABCG2 function by modifying its substrate specificity and its influx/efflux
      rates. This study also demonstrates that flow cytometry constitutes a powerful
      tool for the kinetic analysis of ABC transporters.

PMID- 15517562
TI  - Loss of GM1 surface expression precedes annexin V-phycoerythrin binding of
      neutrophils undergoing spontaneous apoptosis during in vitro aging.
AB  - BACKGROUND: Apoptosis of neutrophil granulocytes is an important determinant of
      the resolution of inflammation. Apoptotic neutrophils undergo specific
      alterations in their receptor profiles. These alterations are likely to
      contribute to the characteristic functional silencing of the dying cells.
      METHODS: By flow cytometry and fluorescence microscopy, we analyzed the
      ganglioside GM1, a lipid raft marker, with respect to its surface expression on
      neutrophil and eosinophil granulocytes. Apoptosis was monitored by morphological
      changes and by the binding of annexin V-phycoerythrin (AxV-PE). RESULTS: GM1,
      which was stained by the cholera toxin subunit B, was found only on neutrophil
      granulocytes; eosinophil granulocytes did not bind cholera toxin subunit B. GM1
      was lost from the surfaces of neutrophils before AxV-PE binding (early
      apoptosis). Surprisingly, GM1 reappeared during the late stages of apoptosis,
      although without functional consequences. GM1 was found on the cell surface and
      in intracellular membranes, whereas CD16 was found only at the cell surface.
      CONCLUSIONS: Loss of surface GM1 is a new marker for the detection of the aging
      of neutrophils. Its loss precedes the binding of AxV-PE of neutrophils.

PMID- 15517564
TI  - Analysis of mitochondrial generation and release of reactive oxygen species.
AB  - BACKGROUND: Reactive oxygen species (ROS) are mainly produced in mitochondria and
      are important contributors to many forms of cell death. ROS also function as
      second messengers within the cell and may constitute a signaling pathway from
      mitochondria to the cytoplasm and nucleus. The aim of the present study was to
      develop a protocol to detect changes in intra- and extramitochondrial releases of
      ROS, which could be used to analyze the role of mitochondria in cell signaling
      and cell death. METHODS: Fluorescence-based assays were used to measure (a) total
      production of ROS, (b) intramitochondrial ROS, (c) extramitochondrial hydrogen
      peroxide, and (d) superoxide outside inverted (inside-out) submitochondrial
      particles. ROS generation in the samples was increased or decreased by the
      addition of different substrates, enzymes, and inhibitors of the electron
      transport chain. RESULTS: The individual assays used were sensitive to increased
      (e.g., after addition of antimycin A; increased signal) and decreased (ROS
      scavenging; decreased signal) levels of ROS. In combination, the assays provided
      information about mitochondrial ROS generation and release dynamics from small
      samples of isolated mitochondria. CONCLUSIONS: The combination of fluorescent
      techniques described is a useful tool to study the role of ROS in cell death and
      in cellular redox signaling.

PMID- 15517566
TI  - Molecular characterization of conditionally immortalized cell lines derived from
      mouse early embryonic inner ear.
AB  - Inner ear sensory hair cells (HCs), supporting cells (SCs), and sensory neurons
      (SNs) are hypothesized to develop from common progenitors in the early embryonic
      otocyst. Because little is known about the molecular signals that control this
      lineage specification, we derived a model system of early otic development:
      conditionally immortalized otocyst (IMO) cell lines from the embryonic day 9.5
      Immortomouse. This age is the earliest stage at which the otocyst can easily be
      separated from surrounding mesenchymal, nervous system, and epithelial cells. At
      9.5 days post coitum, there are still pluripotent cells in the otocyst, allowing
      for the eventual identification of both SN and HC precursors--and possibly an
      elusive inner ear stem cell. Cell lines derived from primitive precursor cells
      can also be used as blank canvases for transfections of genes that can affect
      lineage decisions as the cells differentiate. It is important, therefore, to
      characterize the "baseline state" of these cell lines in as much detail as
      possible. We characterized seven representative "precursor-like" IMO cell
      populations and the uncloned IMO cells, before cell sorting, at the molecular
      level by polymerase chain reaction (PCR) and immunocytochemistry (IHC), and one
      line (IMO-2B1) in detail by real-time quantitative PCR and IHC. Many of the
      phenotypic markers characteristic of differentiated HCs or SCs were detected in
      IMO-2B1 proliferating cells, as well as during differentiation for up to 30 days
      in culture. These IMO cell lines represent a unique model system for studying
      early stages of inner ear development and determining the consequences of
      affecting key molecular events in their differentiation.

PMID- 15517567
TI  - Fish as bioindicators to assess the effects of pollution in two southern
      Brazilian rivers using the Comet assay and micronucleus test.
AB  - Industrial effluents, agricultural runoff, and municipal wastewaters contain
      unknown substances and complex mixtures that are released into the environment
      and can lead to contamination of surface and subsurface waters. In the present
      report, we have used the alkaline Comet assay and the micronucleus (MN) test to
      detect the genotoxicity due to multiple sources of pollution in the peripheral
      blood of two native estuarine fish (mullet and sea catfish) and evaluated
      possible interactive genotoxic effects from multiple contaminants and the
      seasonal variation of the genotoxicity. Mullet and sea catfish were captured in
      the Tramandai and Mampituba Rivers in the southern Brazilian state of Rio Grande
      do Sul. Reference animals were obtained from the Armazem lagoon. Fish captured in
      the two estuaries during the four seasons over a period of 2 years had increased
      levels of DNA damage and MN frequencies relative to the reference fish. In
      general, the alkaline Comet assay was more sensitive to the genotoxicity of the
      river contaminants than the MN test. The Comet assay demonstrated significant
      differences in fish captured at different seasons and at the two river sites,
      while the MN test showed significant differences only for the annual average for
      mullet from both sites and fish from the control site. The increases in DNA
      damage appear to be related to the increase in the number of people in the towns
      close to the study areas during the warm spring and summer seasons. Although no
      specific cause-effect relationships were established, comparison of the chemical
      contaminants and physical variations in the rivers with the genotoxicity data
      indicate that there may be some association between hydrocarbons, metals, pH, and
      water temperature and the level of damaged cells observed in mullet and sea
      catfish from the Tramandai and Mampituba estuaries.

PMID- 15517568
TI  - Examination of the potential genotoxicity of pure capsaicin in bacterial
      mutation, chromosome aberration, and rodent micronucleus tests.
AB  - There is widespread dietary exposure to capsaicin in the form of chili peppers,
      while capsaicin's analgesic qualities have led to increased use of a topical
      herbal remedy in various impure forms. Most recently, injection of pure capsaicin
      has been proposed as a means of relieving a variety of debilitating diseases, in
      which case tissues would receive relatively high and direct exposure. The purpose
      of the present study, where a series of standard assays were performed in
      accordance with the Organisation for Economic Cooperation and Development
      guidance, was to clarify earlier conflicting reports concerning potential
      genotoxicity of capsaicin prior to administering it to patients in an injectable
      form. The results confirm the absence of genotoxic activity of high-purity
      capsaicin in the bacterial mutation and chromosome aberration tests. In addition,
      no evidence of cytotoxicity or genotoxicity was seen in the rat bone marrow
      micronucleus test, where systemic exposure to pure capsaicin was achieved using
      the subcutaneous route and a rising dose toleration protocol. It is concluded
      that pure capsaicin is not active in the standard battery of genotoxicity assays
      recommended by the International Conference on Harmonisation for evaluation of
      new medicines; earlier reported in vitro genotoxic activity is probably
      associated with mutagenic impurities in commercial grades of the material.

PMID- 15517570
TI  - Three-color labeling method for flow cytometric measurement of cytogenetic damage
      in rodent and human blood.
AB  - Experiments described herein were designed to evaluate the performance
      characteristics of a flow cytometry-based system that scores the incidence of
      peripheral blood micronucleated reticulocytes (MN-RETs). These procedures
      represent the continued refinement of a previously reported anti-CD71-based
      method (Dertinger et al. [1996]: Mutat Res 371:283-292), with the following
      modifications: incorporation of a third fluorescent label to exclude platelets
      from the MN-RET region, and use of a CD71-associated fluorescence thresholding
      technique to increase data acquisition rates. Mouse, rat, and human blood samples
      were analyzed using both the previously described two-color procedure (anti-CD71
      FITC and propidium iodide) and a newly developed three-color technique (which
      adds an antiplatelet-PE antibody). The rodent specimens were also evaluated by
      standard microscopy procedures (acridine orange staining). Mouse blood was
      collected via heart puncture of vehicle- and 5-fluorouracil-treated CD-1 mice;
      blood samples from saline-treated Sprague-Dawley rats were collected from the
      tail vein and via heart puncture. Rodent blood samples were analyzed by both the
      two- and three-color methods. Human blood specimens, obtained via arm
      venipuncture from cancer patients undergoing radiation therapy, were analyzed for
      MN-RETs using the two-color method. Subsequently, blood samples from a single
      chemotherapy patient were analyzed by both the two- and three-color methods.
      Finally, the chemotherapy patient blood samples and blood samples from 15 healthy
      volunteers were evaluated at very high densities in conjunction with a CD71
      associated fluorescence thresholding technique. Results of these investigations
      showed that data from mouse blood analyzed by the two- and three-color procedures
      correlated well with microscopy data (r values = 0.917 and 0.937 for the two- and
      three-color methods, respectively); all three methods confirmed the genotoxicity
      of 5-FU. Data from rat tail vein samples showed improved reproducibility with the
      three-color technique, but no significant difference between the two techniques
      was seen with the heart puncture specimens. Human blood analyzed according to the
      two-color procedure produced unreliable results, as platelets and platelet
      aggregates impacted the rare MN-RET scoring region. The three-color technique
      effectively overcame this problem and produced reproducible measurements that
      fell within expected ranges. For human blood analyses, the high cell density/CD71
      thresholding technique provided significant improvements over the low-density
      technique, as it allowed data acquisition to occur approximately six times faster
      with no loss of sensitivity.

PMID- 15517571
TI  - Restricted innervation of uterus and placenta during pregnancy: evidence for a
      role of the repelling signal Semaphorin 3A.
AB  - Because data from the literature suggest a lack of innervation of the placenta,
      we have investigated placenta, umbilical cord, and uterus to identify the
      molecules that play a role in regulating innervation in these organs. Neuropilin
      1 and Plexin-A1 are cell surface proteins that form a receptor complex for
      Semaphorin 3A (Sema 3A), a secreted molecule mediating repelling signals for
      axonal growth cones. We have analyzed the expression of Neuropilin-1, Plexin-A1,
      and Semaphorin 3A in the above-mentioned tissues on the hypothesis that these
      molecules could regulate innervation in these organs during gestation. We found
      that nervous fibers are only present in the proximal part of the umbilical cord,
      close to the newborn, and in nongestational uterine tissues. In contrast, nervous
      fibers are not present in the distal segment of the umbilical cord, in the
      placenta and in the uterine tissues during gestation. We also found that Sema 3A
      receptors, Neuropilin-1 and Plexin-A1, are expressed by the nervous fibers of the
      proximal part of the umbilical cord, whereas Sema 3A is secreted in the umbilical
      cord, in the placenta, and in gestational uterine tissues. We report that a
      factor secreted in the umbilical cord induces the collapse of neurite growth
      cones in vitro and provide evidence that this factor is Sema 3A. In summary, our
      results suggest that the chemorepulsive signals mediated by Sema 3A play an
      important role in preventing nerve fibers growth in the umbilical cord and in
      gestational uterine tissues. The inhibition of nerve growth into the myometrium
      as well as into the placenta could be considered fundamental processes to
      preserve the fetus from external stressful events.

PMID- 15517573
TI  - Utility of automated counting to determine absolute neutrophil counts and
      absolute phagocyte counts for pediatric cancer treatment protocols.
AB  - BACKGROUND: Absolute neutrophil counts (ANCs) and absolute phagocyte counts
      (APCs) are used to guide cancer treatment. Although automated counting could
      replace manual counting, data showing correlations are lacking. By analyzing
      blood samples from children undergoing cancer treatment, the authors determined
      whether ANCs and APCs obtained by automated methods correlated positively with
      ANCs and APCs obtained manually. METHODS: The authors analyzed 3640 consecutive
      peripheral blood samples. Leukocyte counts determined by Beckman-Coulter Gen-S or
      HmX analyzers (Beckman-Coulter, Miami, FL) were used to calculate counts obtained
      by automated or manual methods. Automated differential counts were obtained by
      automated analyzers and manual differential counts were performed by medical
      technologists. Counts underwent linear regression analysis. The authors evaluated
      5 cutoff values for ANCs and APCs commonly used in decision-making related to
      cancer treatment: 300/muL, 500/muL, 750/muL, 1000/muL, and 1500/muL. Manually
      determined ANCs and APCs served as standards to determine the sensitivity,
      specificity, positive and negative predictive values, and kappa coefficient for
      automated counting. RESULTS: R(2) values were 0.81 for ANCs determined by manual
      and automated methods and 0.84 for APCs determined by both methods. The
      specificity of the automated method was > 90% for all ranges of ANCs and APCs,
      except one (APCs < 300/muL). There was excellent agreement (kappa > 0.9) between
      ANCs determined by manual and automated methods and APCs calculated by both
      methods. CONCLUSIONS: Automated methods of determining ANCs and APCs for children
      undergoing cancer treatment were reliable and can replace manual counting. Blood
      smear examination to validate ANCs and APCs determined by automated methods was
      needed only in selected cases.

PMID- 15517574
TI  - Patient expectation is a strong predictor of severe nausea after chemotherapy: a
      University of Rochester Community Clinical Oncology Program study of patients
      with breast carcinoma.
AB  - BACKGROUND: Patients may use their past experiences with nausea, as well as
      information about the incidence of nausea from chemotherapy that other patients
      have experienced, to form a prediction, or response expectancy, of nausea from
      their own upcoming chemotherapy. Mounting evidence suggests that these
      expectancies relating to nausea are significant predictors, and, likely,
      contributing factors to the development of treatment-related nausea. METHODS: The
      patients in the current study were participants in the control arm of a
      multicenter clinical trial conducted between November 1999 and July 2001 by the
      University of Rochester Community Clinical Oncology Program. All patients in the
      current report were age >/= 18 years and were about to begin a first cancer
      treatment regimen containing doxorubicin. RESULTS: Expectancy of nausea assessed
      before patients received their first doxorubicin-based chemotherapy treatment was
      found to be a strong predictor of subsequent nausea and in fact was stronger than
      previously reported predictive factors, including age, nausea during pregnancy,
      and susceptibility to motion sickness. Women who believed it was "very likely"
      that they would have severe nausea from chemotherapy were five times more likely
      to experience severe nausea than fellow patients who thought its occurrence would
      be "very unlikely." CONCLUSIONS: Further studies confirming an expectancy of
      nausea as a risk factor are warranted as are studies examining the benefit to a
      patient's quality of life from modifying antiemetic treatment guidelines to take
      into account symptom expectancies. Finally, ethically acceptable interventions
      that are designed to reduce patients' nausea expectancies or increase their
      expectancies of nausea control should be developed and studied.

PMID- 15517575
TI  - Parathyroid hormone-related protein expression is correlated with clinical course
      in patients with glial tumors.
AB  - BACKGROUND: Parathyroid hormone-related protein (PTHrP) expression modulates cell
      survival in a number of human solid tumors. Although PTHrP is expressed in normal
      developing and neoplastic central nervous system tissue, clinical data indicating
      the importance of this protein with respect to local control and/or survival in
      patients with glial tumors are scarce. METHODS: Using a standard immunoperoxidase
      technique, the authors examined PTHrP expression in a population of 51 patients
      with Daumas-Duport Grade II-IV astrocytomas over a 15-year period. Both local
      control and survival were calculated from the date of definitive irradiation to
      the last time of known follow-up examination using the actuarial method. PTHrP
      expression was scored on examination under 40x magnification, with the incidence
      of cellular staining averaged over 10 high-power fields. The intensity and extent
      of staining were characterized semiquantitatively using the standard World Health
      Organization classification criteria. The median follow-up duration was
      approximately 5.5 years. Multivariate analyses were performed to ascertain the
      statistical significance of several standard clinicohistopatholgic factors
      (Karnofsky functional status, age, gender, extent of surgical resection,
      radiotherapy dose, grade, and PTHrP expression) with respect to local control and
      survival. P < 0.05 was considered indicative of statistical significance.
      RESULTS: Patients with high levels of PTHrP expression had significantly lower
      glial tumor local control rates and corresponding decreases in progression-free
      and overall actuarial survival after definitive irradiation (P < 0.01). In a Cox
      3-variable model, the PTHrP staining score was independent of tumor grade or
      Karnofsky functional status. It is notable that the strongest predictor of
      survival was tumor grade (P < 0.001). CONCLUSIONS: PTHrP may be an important
      adjunct to standard immunopathologic criteria in the determination of glial tumor
      responses. A number of mechanisms were explored to derive a more mechanistic
      understanding of these translational results. Subsequent prospective studies
      involving larger patient populations will be necessary before findings can be
      translated to clinical practice.

PMID- 15517576
TI  - The role of fluorodeoxyglucose positron emission tomography in cervical lymph
      node metastases from an unknown primary tumor.
AB  - BACKGROUND: The authors performed a comprehensive review of the efficacy of
      fluorodeoxyglucose positron emission tomography (FDG-PET) in the detection of
      primary tumors in patients with cervical metastases from unknown primary tumors.
      METHODS: Sixteen studies (involving a total of 302 patients) published between
      1994 and 2003 were reviewed. These studies evaluated the role of FDG-PET in the
      detection of unknown primary tumors after conventional workup. In all studies,
      conventional workup included either panendoscopy or computed tomographic/magnetic
      resonance imaging, and in 10 of 16 studies, both of these diagnostic techniques
      were performed before diagnosis. RESULTS: The overall sensitivity, specificity,
      and accuracy rates of FDG-PET in detecting unknown primary tumors were 88.3%,
      74.9%, and 78.8%, respectively. Furthermore, FDG-PET detected 24.5% of tumors
      that were not apparent after conventional workup. FDG-PET imaging also led to the
      detection of previously unrecognized metastases in 27.1% of patients (regional,
      15.9%; distant, 11.2%). FDG-PET had notably low specificity and a high false
      positive rate (39.3%) in the tonsils. In contrast, the false-positive rates for
      FDG-PET of the base of tongue and hypopharynx were only 21.4% and 8.3%,
      respectively. FDG-PET exhibited decreased sensitivity to tumors in the base of
      tongue (81.5%). The sensitivity of this technique at other sites was 90.5%.
      CONCLUSIONS: FDG-PET detected primary tumors that went undetected by other
      modalities in approximately 25% of cases and was sensitive in the detection of
      previously unrecognized regional or distant metastases in 27% of cases. FDG-PET
      had low specificity for tonsillar tumors and low sensitivity for base-of-tongue
      malignancies.

PMID- 15517578
TI  - Expression of the pro-apoptotic protein ARTS in astrocytic tumors: correlation
      with malignancy grade and survival rate.
AB  - BACKGROUND: Apoptosis (i.e., programmed cell death) plays a major role in the
      development of astrocytic tumors, which are the most common tumors of the central
      nervous system. ARTS, a proapoptotic protein that is localized in the
      mitochondria, promotes apoptosis by functioning as an XIAP antagonist and a
      caspase activator. METHODS: To investigate the role of ARTS in astrocytoma, the
      authors examined protein expression and apoptotic activity in 72 astrocytic
      tumors, which included low-grade astrocytomas, anaplastic astrocytomas, and
      glioblastomas. RESULTS: Whereas normal astrocytes did not express the ARTS
      protein, astrocytoma cells strongly expressed ARTS, and the expression of this
      protein increased with increasing tumor grade. Furthermore, increased levels of
      ARTS were significantly associated with higher rates of apoptosis (as measured
      using the terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate
      nick end-labeling [TUNEL] assay as well as an immunohistochemical staining assay
      for active caspase-3) in these tumors. Levels of two other apoptosis-related
      proteins, p53 and Bcl-2, also were examined using immunohistochemical methods;
      ARTS expression was found to be positively correlated with expression of the
      former and negatively correlated with expression of the latter, which is known to
      possess antiapoptotic activity. CONCLUSIONS: The results of the current study
      suggest that ARTS levels reliably reflect the ability of cells to undergo
      apoptosis, which serves as a defense mechanism against the development and
      progression of astrocytoma. Furthermore, ARTS expression, when taken into
      consideration in combination with tumor grade, was the only independent predictor
      of survival identified in the current analysis. Thus, the authors conclude that
      ARTS may possess utility as a prognostic marker, as well as a therapeutic tool,
      for patients with astrocytoma.

PMID- 15517579
TI  - Assembly and remodeling of the fibrillar fibronectin extracellular matrix during
      gastrulation and neurulation in Xenopus laevis.
AB  - Fibronectin, a major component of the extracellular matrix is critical for
      processes of cell traction and cell motility. Whole-mount confocal imaging of the
      three-dimensional architecture of the extracellular matrix is used to describe
      dynamic assembly and remodeling of fibronectin fibrils during gastrulation and
      neurulation in the early frog embryo. As previously reported, fibrils first
      appear under the prospective ectoderm. We describe here the first evidence for
      regulated assembly of fibrils along the somitic mesoderm/endoderm boundary as
      well as at the notochord/somitic mesoderm boundary and clearing of fibrils from
      the dorsal and ventral surfaces of the notochord that occurs over the course of a
      few hours. As gastrulation proceeds, fibrils are restored to the dorsal surface
      of the notochord, where the notochord contacts the prospective floor plate. As
      the neural folds form, fibrils are again remodeled as deep neural plate cells
      move medially. The process of neural tube closure leaves a region of the ectoderm
      overlying the neural crest transiently bare of fibrils. Fibrils are assembled
      surrounding the dorsal surface of the neural tube as the neural tube lumen is
      restored.

PMID- 15517581
TI  - Gene expression in the axolotl germ line: Axdazl, Axvh, Axoct-4, and Axkit.
AB  - Primordial germ cells (PGCs) in embryos of mammals and urodele amphibians are
      formed by induction in the absence of germ plasm. We describe expression of four
      germ cell-related genes through the germ cell cycle of the axolotl. The orthologs
      of vasa and daz-like are up-regulated in PGCs of tail bud embryos before the
      gonad forms and are expressed throughout the female germ cell cycle. Mammalian
      Oct-4 is a marker of pluripotency in embryonic cells. Axolotl Oct-4 has higher
      homology to Oct-4 than that found in other vertebrates. It is expressed in the
      equivalent of the mouse epiblast, in the posterior mesoderm of late gastrulae
      that gives rise to PGCs, and in diplotene growing oocytes, but not in presumptive
      PGCs after gastrulation. Finally, a c-kit homolog is expressed in gonadal oogonia
      and growing oocytes as in mice but is also not found in PGCs. The expression
      pattern in urodele gonadal germ cells is similar to that of other vertebrates,
      although the pattern in pregonadal PGCs is distinctly different from that of
      mice. We conclude that PGCs are restricted to the germ line later in urodeles
      than in mice or lack migration and proliferation programs.

PMID- 15517582
TI  - Sinonasal malignancies with neuroendocrine differentiation: patterns of failure
      according to histologic phenotype.
AB  - BACKGROUND: Sinonasal neuroendocrine tumors are rare malignancies that are
      represented by a spectrum of histologies, including esthesioneuroblastoma (ENB),
      sinonasal undifferentiated carcinoma (SNUC), neuroendocrine carcinoma (NEC), and
      small cell carcinoma (SmCC). The authors reviewed their institutional experience
      to determine whether sinonasal neuroendocrine tumors of different histologies
      have distinct clinical characteristics that warrant individualized treatment
      approaches. METHODS: The authors treated 72 adults with pathologically proven,
      nonmetastatic, primary sinonasal neuroendocrine tumors from 1982 to 2002. There
      were 31 patients with ENB, 16 patients with SNUC, 18 patients with NEC, and 7
      patients with SmCC. Patients with ENB usually were treated with local therapy
      alone (surgery and/or radiotherapy); only 3 of 31 patients (9.7%) received
      treatment (radiation) to regional lymphatics, and only 5 of 31 patients (16.1%)
      received chemotherapy. In contrast, patients with non-ENB histologies usually
      received chemotherapy (10 of 16 patients with SNUC, 12 of 18 patients with NEC,
      and 5 of 7 patients with SmCC), and nonsurgical locoregional therapy was used
      more frequently (6 of 16 patients with SNUC, 4 of 18 patients with NEC, and 5 of
      7 patients with SmCC). RESULTS: The median follow-up for surviving patients was
      81.5 months (range, 6-266 months). The Kaplan-Meier estimate of overall survival
      at 5 years was 93.1% for patients with ENB, 62.5% for patients with SNUC, 64.2%
      for patients with NEC, and 28.6% for patients with SmCC (P = 0.0029; log-rank
      test). The local control rate at 5 years also was superior for patients who had
      ENB (96.2%) compared with patients who had SNUC (78.6%), NEC (72.6%), or SmCC
      (66.7%) (P = 0.04). The regional failure (RF) rate at 5 years was 8.7% for
      patients with ENB, 15.6% for patients with SNUC, 12.9% for patients with NEC, and
      44.4% for patients with SmCC. Additional late events increased the RF rate for
      patients with ENB to 31.9% at 10 years. The distant metastasis rate at 5 years
      was 0.0% for patients with ENB, 25.4% for patients with SNUC, 14.1% for patients
      with NEC, and 75.0% for patients with SmCC. CONCLUSIONS: This spectrum of
      malignancies with neuroendocrine features shares a common site of origin within
      the head and neck, but their natural histories appear to diverge into two main
      groups: ENB and non-ENB. Patients with ENB had excellent local and distant
      control rates with local therapy alone. Given the higher rates of systemic
      failure for patients with SNUC, NEC, and SmCC, the authors favor the use of
      combined-modality therapy for these patients.

PMID- 15517583
TI  - Xenopus flotillin1, a novel gene highly expressed in the dorsal nervous system.
AB  - The two paralogues of the Xenopus flotillin1 gene (flotillin1A and flotillin1B),
      which encodes a putative membrane-associated protein, were cloned from egg,
      cleavage, and tadpole cDNA libraries. Both mRNAs are present during oogenesis and
      cleavage stages. After the onset of zygotic transcription, flotillin1 transcripts
      are first expressed throughout the embryonic ectoderm and become enhanced in the
      presumptive neural ectoderm as the neural plate forms. As the neural tube forms
      and differentiates, flotillin1 transcripts become enriched in the dorsal half,
      with particularly high expression in dorsal primary neurons. At early tail bud
      stages, there is additional expression in the paraxial mesoderm. At late tail bud
      stages, flotillin1A is expressed in branchial arch mesenchyme, the overlying
      branchial ectoderm and in dorsal somitic mesoderm, whereas flotillin1B expression
      is more restricted in the dorsal neural tube and head sensory structures. This
      report is the first comprehensive developmental description in any animal of the
      expression pattern of this gene, whose protein product in several systems plays
      important roles in signal transduction events.

PMID- 15517584
TI  - Nodal/activin signaling establishes oral-aboral polarity in the early sea urchin
      embryo.
AB  - Components of the Wnt signaling pathway are involved in patterning the sea urchin
      primary or animal-vegetal (AV) axis, but the molecular cues that pattern the
      secondary embryonic axis, the aboral/oral (AO) axis, are not known. In an
      analysis of signaling molecules that influence patterning along the sea urchin
      embryonic axes, we found that members of the activin subfamily of transforming
      growth factor-beta (TGF-beta) signaling molecules influence the establishment of
      AO polarities in the early embryo. Injection of activin mRNAs into fertilized
      eggs or treatment with exogenously applied recombinant activin altered the
      allocation of ectodermal fates and ventralized the embryo. The phenotypes
      observed resemble the ventralized phenotype previously reported for NiCl2, a
      known disrupter of AO patterning. Sensitivity to exogenous activin occurs between
      fertilization and the late blastula stage, which is also the time of highest
      NiCl2 sensitivity. These results argue that specification of fates along the
      embryonic AO axis involves TGF-beta signaling. To further examine TGF-beta
      signaling in these embryos, we cloned an endogenous TGF-beta from sea urchin
      embryos that is a member of the activin subfamily, SpNodal, and show through gain
      of function analysis that it recapitulates results obtained with exogenous
      activins and NiCl2. The expression pattern of SpNodal is consistent with a role
      for nodal signaling in the establishment of fates along the AO axis. Loss of
      function experiments using SpNodal antisense morpholinos also support a role for
      SpNodal in the establishment of the AO axis.

PMID- 15517585
TI  - Targeted insertion of the Cre-recombinase gene at the phenylethanolamine n
      methyltransferase locus: a new model for studying the developmental distribution
      of adrenergic cells.
AB  - To evaluate the developmental distribution of adrenergic cells in vivo, we
      inserted the Cre-recombinase gene into the locus encoding for the epinephrine
      biosynthetic enzyme phenylethanolamine n-methyltransferase (Pnmt) and crossed
      these Pnmt-Cre mice with ROSA26 reporter (R26R) mice to activate LacZ (encoding
      beta-galactosidase) expression in cells that were selectively derived from the
      adrenergic lineage. Our data show the following: (1) Insertion of Cre-recombinase
      into the Pnmt locus created a functional knockout of Pnmt expression with
      concomitant loss of epinephrine in homozygous Pnmt(Cre/Cre) mice; (2) Despite the
      reduction in Pnmt expression and epinephrine production in Pnmt(Cre/Cre) mice,
      these mice were viable and fertile, with no apparent developmental defects; (3)
      When crossed with R26R mice, Pnmt-Cre activation of LacZ expression faithfully
      recapitulated Pnmt expression in vivo; and (4) LacZ expression was activated in
      substantial numbers of pacemaking, conduction, and working cardiomyocytes.

PMID- 15517586
TI  - Isolation of chicken homolog of the FOXL2 gene and comparison of its expression
      patterns with those of aromatase during ovarian development.
AB  - Mutations in the forkhead transcription factor gene FOXL2 are involved in ovarian
      failure, which occurs in human BPES syndrome. This syndrome presents a sexually
      dimorphic expression, specific to the ovary in several vertebrates. We cloned the
      open reading frame of chicken FOXL2 (cFoxL2) and studied cFoxL2 expression in
      developing gonads and during adulthood to examine the role of FOXL2 in ovarian
      differentiation and function in birds. The spatial and temporal dynamics of
      cFoxL2 and aromatase expression were analyzed in parallel by using real-time
      quantitative reverse transcriptase-polymerase chain reaction and
      immunohistochemistry in attempt to investigate the possible role of cFoxL2 in the
      regulation of aromatase. The expression patterns of cFoxL2 and aromatase
      transcripts were highly correlated during the sex-differentiation period (4.7
      12.7 days of incubation). Aromatase and cFoxL2 proteins were colocalized in the
      medullar part of female gonads on embryonic day 14. Fourteen days after hatching,
      cFoxL2 protein was mainly detected in granulosa cells of developing follicles. In
      adult ovary follicular envelopes, apart from granulosa cells, cFoxL2 transcript
      and protein were detected at lower levels in theca cells where aromatase was
      present. A high level of cFoxL2 transcription was also observed in maturing and
      ovulated oocytes. Our results confirm that FoxL2 is an early regulator of ovarian
      development in birds and may be involved in aromatase transcription regulation.

PMID- 15517587
TI  - Partition of protein solvation into group contributions from molecular dynamics
      simulations.
AB  - Linear response theory coupled to molecular dynamics simulations with an explicit
      solvent representation is used to derive fractional contributions of amino acid
      residues to the solvation of proteins. The new fractional methods developed here
      are compared with standard approaches based on empirical 1D and 3D statistical
      potentials, as well as with estimates obtained from the analysis of classical
      molecular interaction potentials. The new fractional methods, which have a clear
      physical basis and explicitly account for the effects due to protein structure
      and flexibility, provide an accurate picture of the contribution to solvation of
      different regions of the protein.

PMID- 15517588
TI  - A combination of HER-2 status and the St. Gallen classification provides useful
      information on prognosis in lymph node-negative breast carcinoma.
AB  - BACKGROUND: Adjuvant chemotherapy for patients with lymph node-negative breast
      carcinoma is being recommended currently based on the St. Gallen classification.
      The prognostic importance of HER-2 status in patients with lymph node-negative
      breast carcinoma has been investigated extensively, with contradictory results.
      The authors investigated the clinical relevance of HER-2 overexpression when
      combined with the St. Gallen classification in lymph node-negative breast
      carcinoma. METHODS: The medical records of patients with breast carcinoma
      negative for lymph node involvement who underwent surgery between January 1995
      and December 2000 at the Seoul National University College of Medicine (Seoul,
      Korea) were reviewed retrospectively. Risk groups based on the St. Gallen
      classification were categorized as average or minimal risk. The prognostic values
      of HER-2 in combination with the St. Gallen classification were analyzed with
      respect to disease-free survival (DFS) rates. RESULTS: A total of 906 patients
      were eligible for analysis. The overall 7-year DFS rate was 87.5%. The 7-year DFS
      rates for patients with HER-2-positive and HER-2-negative tumors were,
      respectively, 77.9% and 91.2% (P = 0.002). The 7-year DFS rates for patients with
      average and minimal risk group were 85.0% and 97.9%, respectively. The authors
      found that HER-2 overexpression significantly predicted the risk of disease
      recurrence (odds ratio = 3.03 [95% confidence interval, 1.63-5.63]). Furthermore,
      when HER-2 status was combined with the St. Gallen classification, the DFS rate
      of the HER-2-positive average risk group was 73.3% compared with 88.4% for the
      HER-2-negative average risk group (P = 0.007). CONCLUSIONS: The combination of
      HER-2 overexpression and the St. Gallen classification was more useful than
      either alone to predict the risk of disease recurrence in patients with lymph
      node-negative breast carcinoma.

PMID- 15517589
TI  - Intratumoral administration of a 1,2-dimyristyloxypropyl-3- dimethylhydroxyethyl
      ammonium bromide/dioleoylphosphatidylethanolamine formulation of the human
      interleukin-2 gene in the treatment of metastatic renal cell carcinoma.
AB  - BACKGROUND: Leuvectin (Vical Inc., San Diego, CA) is a gene transfer product in
      which a plasmid encoding the human interleukin-2 (IL-2) gene is complexed with
      the cationic lipid 1,2-dimyristyloxypropyl-3-dimethylhydroxyethyl ammonium
      bromide/dioleoylphosphatidylethanolamine (DMRIE/DOPE). In the current study, the
      authors investigated the safety and efficacy of in situ vaccination with
      Leuvectin in patients with metastatic renal cell carcinoma. METHODS: Thirty-one
      patients with metastatic renal cell carcinoma were treated with intratumorally
      administered Leuvectin at doses ranging from 0.75 to 4 mg. These patients
      subsequently were evaluated for response and for treatment-related toxicity.
      RESULTS: Treatment was well tolerated: no Grade 3 or 4 toxicities were observed
      in association with the study agent. Documented side effects included Grade 1
      pain at the injection site (20%); mild (i.e., Grade 1 or 2) constitutional
      symptoms, including malaise/myalgia, low-grade fever, and chills (74%); Grade 1
      fatigue (19%); Grade 1 or 2 nausea (10%); and Grade 2 allergy (1 occurrence). Two
      patients experienced partial responses, which endured for 32 months and 6 years,
      respectively, and 1 patient currently is experiencing a pathologic complete
      response, which, to date, has persisted for 50 months; thus, the overall response
      rate was 10%. In addition, 7 patients (23%) experienced disease stabilization for
      a median of 8 months (range, 4-48 months). The median duration of survival from
      the start of Leuvectin treatment was 11 months (range, 2-72 months), with a 1
      year survival rate of 48% and a 3-year survival rate of 19%. Laboratory analysis
      of tumor samples revealed the presence of IL-2 plasmid DNA in six of eight
      patients posttreatment, increased IL-2 expression in tumor cells in four of eight
      patients posttreatment, and increased tumor infiltration by CD8-positive
      lymphocytes in five of eight patients posttreatment. CONCLUSIONS: Immunotherapy
      with intratumorally administered Leuvectin is safe and can lead to durable
      objective responses in patients with metastatic renal cell carcinoma.

PMID- 15517590
TI  - Binding of glutamine to glutamine-binding protein from Escherichia coli induces
      changes in protein structure and increases protein stability.
AB  - Glutamine-binding protein (GlnBP) from Escherichia coli is a monomeric protein
      localized in the periplasmic space of the bacterium. It is responsible for the
      first step in the active transport of L-glutamine across the cytoplasmic
      membrane. The protein consists of two similar globular domains linked by two
      peptide hinges, and X-ray crystallographic data indicate that the two domains
      undergo large movements upon ligand binding. Fourier transform infrared
      spectroscopy (FTIR) was used to analyze the structure and thermal stability of
      the protein in detail. The data indicate that glutamine binding induces small
      changes in the secondary structure of the protein and that it renders the
      structure more thermostable and less flexible. Detailed analyses of IR spectra
      show a lower thermal sensitivity of alpha-helices than beta-sheets in the protein
      both in the absence and in the presence of glutamine. Generalized two-dimensional
      (2D) analyses of IR spectra reveal the same sequence of unfolding events in the
      protein in the absence and in the presence of glutamine, indicating that the
      amino acid does not affect the unfolding pathway of the protein. The data give
      new insight into the structural characteristics of GlnBP that are useful for both
      basic knowledge and biotechnological applications.

PMID- 15517591
TI  - Pilot association study of the beta-glucocerebrosidase N370S allele and
      Parkinson's disease in subjects of Jewish ethnicity.
AB  - Mutations in the beta-glucocerebrosidase gene cause Gaucher's disease, one of the
      most common lysosomal lipid storage diseases in the Ashkenazi Jewish population.
      The occurrence of parkinsonism in patients with Type 1 Gaucher's disease has been
      noted previously. In this pilot study, we evaluated a possible association
      between Parkinson's disease (PD) and the beta-glucocerebrosidase gene N370S
      allele (nt.1226 A>G) in 160 Parkinson's disease patients and 92 controls of
      Jewish ethnicity. We observed a higher frequency of the N370S genotype in PD
      cases (NS and SS, 10.7%) compared to controls (NS and SS 4.3%); however, the
      difference was not statistically significant (chi(2) = 3.4, P = 0.2). A total of
      17 PD cases carry the N370S allele, including 2 homozygotes and 15 heterozygotes.
      The N370S allele (nt.1226 A>G) may be associated with PD in patients of Jewish
      ethnicity and should be examined in a larger study.

PMID- 15517592
TI  - Analysis of the glucocerebrosidase gene in Parkinson's disease.
AB  - Parkinson's disease (PD) is a common progressive neurodegenerative disorder
      characterized clinically by a combination of motor symptoms. Identifying novel PD
      genetic risk factors is important for understanding its pathogenesis. A recent
      study suggested that up to 21% of subjects with PD may have mutations in the
      glucocerebrosidase (GBA) gene. We investigated the GBA gene for mutations in 88
      PD cases and 122 normal controls and detected the presence of heterozygous GBA
      mutations in 5 PD cases and in 1 control. Sequencing of the entire open reading
      frame of the GBA gene in a subset of 25 cases with early-onset PD (<50 years of
      age) uncovered no additional mutations. Our results demonstrate a marginally
      significant association of GBA mutations with PD and suggest that variations in
      the GBA gene may constitute a rare susceptibility factor for PD (P = 0.048).

PMID- 15517594
TI  - Differentiation and drug resistance relationships in leukemia cells.
AB  - It is well established that the effectiveness of anticancer drugs may result from
      combined cytotoxic and differentiation activities on tumor cells. Also,
      differentiating agents are able to alter the susceptibility of cancer cells to
      antineoplastic drug therapy. However, the acquisition and/or development of drug
      resistance that frequently appears in anticancer treatment can impair these
      interactions between differentiation agents and cytotoxic drugs. In the present
      study, we report that the acquisition of resistance to anthracyclines in two
      humans, promyeolocytic leukemia HL-60 and eythroleukemia K562 cell lines, results
      in a restricted maturation process induced by differentiating agents with respect
      to that exhibited by their corresponding drug-sensitive counterparts.
      Interestingly, differentiating agents are able to decrease the overexpression of
      drug-efflux pumps as it is the case of MRP1 in the resistant HL-60 cells, thus
      increasing the sensitivity of cells to drug treatment. In addition,
      susceptibility of the drug-sensitive cells to certain apoptotic stimuli is
      significantly reduced after differentiation. The results here reported indicate
      complex interactions between cytotoxic (drug therapy) and non-cytotoxic
      (differentiation) cancer treatments, which should be taken into account to
      improve therapeutic efficiency.

PMID- 15517593
TI  - PTEN expression elicited by EGR-1 transcription factor in calyculin A-induced
      apoptotic cells.
AB  - PTEN is a tumor suppressor gene encoding a phosphatase that negatively regulates
      cell survival mediated by the PI3-kinase-Akt pathway. The gene for transcription
      factor EGR-1 is an early response gene essential for cellular growth,
      proliferation, and differentiation. Protein phosphatase inhibitors including
      calyculin A and okadaic acid are potent inducers of apoptosis in several cell
      lines; however, the molecular mechanisms underlying their action are unknown. The
      purpose of this study was to examine the expression of PTEN and EGR-1 and the
      phosphorylation status of EGR-1 and Akt in calyculin A-treated human squamous
      carcinoma cells (SCCTF). Phosphorylation of EGR-1 and upregulation of PTEN
      expression were observed to occur in SCCTF cells treated with calyculin A in time
      and dose-dependent fashions. The level of phosphorylated Akt decreased as the
      expression of PTEN protein increased in the calyculin A-treated SCCTF cells.
      Calyculin A-stimulated expression of EGR-1 and PTEN might be p53 independent,
      because the expression of them was also detected in p53-null Saos-2 cells. RNA
      interference using double-stranded RNA specific for the EGR-1 gene inhibited not
      only EGR-1 expression but also PTEN expression in SCCTF cells treated or not with
      calyculin A. Calyculin A induced nuclear fragmentation and chromatin condensation
      in SCCTF cells. The present results suggest that the level of PTEN expression and
      the phosphorylation status of Akt were associated with apoptosis induced by
      calyculin A. These observations also support the view that EGR-1 regulates PTEN
      expression in the initial steps of the apoptotic pathway.

PMID- 15517595
TI  - Role of AKT/PKB signaling in fibroblast growth factor-1 (FGF-1)-induced
      angiogenesis in the chicken chorioallantoic membrane (CAM).
AB  - Transfection of chicken chorioallantoic membranes (CAMs) with a chimeric secreted
      version of fibroblast growth factor-1 (sp-FGF-1) gene construct leads to a
      significant increase in vascularization. Though FGF-stimulated angiogenesis has
      been extensively studied, the molecular mechanisms regulating FGF-1-induced
      angiogenesis are poorly understood in vivo. This study was designed to
      investigate the role of the AKT (PKB) kinase signaling pathway in mediating sp
      FGF-1-induced angiogenesis in the chicken CAM. The involvement of the AKT pathway
      was demonstrated by up-regulation of AKT1 mRNA expression in sp-FGF-1 compared to
      vector alone control transfected CAMs as demonstrated by real-time RT-PCR.
      Western analysis using an antibody specific to the activated AKT (phosphorylated
      AKT), demonstrated an increase in AKT activity in sp-FGF-1 compared to vector
      control transfected CAMs. More importantly, the AKT inhibitor ML-9 significantly
      reduced sp-FGF-1-induced angiogenesis in CAMs. These results indicate that AKT
      signaling plays a role in FGF-1-stimulated angiogenesis in vivo and the AKT
      pathway may serve as a therapeutic target for angiogenesis-associated diseases.

PMID- 15517596
TI  - Bone marrow stromal cells express two distinct splice variants of ER-alpha that
      are regulated by estrogen.
AB  - Estrogen plays a critical role in bone metabolism in both sexes. While the major
      action of estrogen is to inhibit bone resorption, it is now clear that early
      osteoblastic (or stromal) cells are a target for estrogen action, mediating the
      effects of estrogen on bone formation as well as resorption. However, little is
      known about the expression or regulation of the estrogen receptor (ER)-alpha in
      these cells. The expression of ER-alpha is regulated by a complex set of
      promoters and ER-alpha splice variants are present in different tissues. Thus, we
      sought to define the ER-alpha splice variants and their regulation by estrogen in
      the mouse bone marrow stromal cell line, ST-2, which can be induced to
      differentiate into mature osteoblasts. ST-2 cells expressed the mRNAs and
      proteins for both the 66 and 46 kDa forms of ER-alpha; the latter lacks the AF-1
      domain and can transduce estrogen signaling in some tissues, while serving as a
      dominant negative receptor in others. Using primers specific for each of the five
      5'-untranslated exons of ER-alpha, we found that ST-2 cells utilized only the
      promoters upstream of exons F and C (in contrast to most reproductive tissues,
      which utilize promoters upstream of virtually all the five exons). Moreover,
      17beta-estradiol (10(-8) M) treatment of ST-2 cells markedly diminished levels of
      the 66 kDa as well as the 46 kDa ER-alpha proteins, largely through suppression
      of the transcript arising from the F1 promoter. These data thus indicate that:
      (1) bone marrow stromal cells express at least two variants of ER-alpha and (2)
      estrogen down regulates the ER-alpha mRNA and protein in these cells.

PMID- 15517597
TI  - Co-localization of poly(ADPR)polymerase 1 (PARP-1) poly(ADPR)polymerase 2 (PARP
      2) and related proteins in rat testis nuclear matrix defined by chemical cross
      linking.
AB  - Poly(ADPR)polymerase 1 and 2 (PARP-1, PARP-2) are nuclear enzymes which function
      is based on specific interactions with DNA and nuclear proteins. PARPs targets
      include proteins involved in DNA replication, repair, and transcription and their
      function can be modulated either by protein-protein interaction with native PARP
      1 and by non-covalent interaction with poly(ADP-ribose) (pADPR) linked to the
      auto-modified PARP-1. Moreover, the association of pADPR and PARP-1 with the
      nuclear matrix (NM) has been reported, based on the poly(ADP-ribosyl)ation of
      nuclear matrix proteins (NMPs). In the present article, by the use of DNA and
      protein cross-linking reactions, by cis-diamminedichloroplatinum II (cDDP) and
      sodium tetrathionate (NaTT) respectively, we present more evidences about the
      association of PARP-1, PARP-2, and PARPs related proteins with the NM. Our
      findings confirmed that NM could be seen as a fraction greatly enriched in
      transcription factors (i.e., C/EBP-beta) and enzymes (DNA Topo II, DNA PK) that
      co-localize with PARP-1 and -2 at the matrix associated regions (MARs) of
      chromatin. Moreover, pADPR contributes to PARP-1 localization at the NM, showing
      that PARP(s) activity co-operates to the functions of this nuclear fraction.

PMID- 15517598
TI  - Osteoblasts lacking the vitamin D receptor display enhanced osteogenic potential
      in vitro.
AB  - 1,25-dihydroxyvitamin D plays an important role in the regulation of osteoblast
      gene expression, regulating the expression of bone matrix proteins as well as
      that of Runx2, a key regulator of osteoblast differentiation. Studies in mice
      lacking the vitamin D receptor (VDR) have revealed that the actions of the VDR on
      the skeleton are not required in the setting of normal mineral ion homeostasis.
      Since paracrine and endocrine factors can compensate for gene defects in vivo,
      studies were performed to determine whether ablation of the VDR alters the
      program of osteoblast differentiation in vitro. Studies in primary calvarial
      cultures revealed that ablation of the VDR enhanced osteoblast differentiation.
      The cells from the VDR null mice exhibited an earlier onset and increased
      magnitude of alkaline phosphatase activity, as well as an earlier and sustained
      increase in mineralized matrix formation, demonstrating that this enhancement
      persists throughout the program of osteoblast differentiation. The expression of
      bone sialoprotein, which enhances mineralization, was also increased in the VDR
      null cultures. To determine whether the increase in osteoblast differentiation
      was associated with an increase in the number of osteogenic progenitors, the
      number of osteoblastic colony forming units (CFU-OB) was evaluated. There was a
      twofold increase in the number of CFU-OB in the cultures isolated from the VDR
      null mice. Furthermore, the VDR null CFU-OB demonstrated an earlier onset and
      higher magnitude of expression of alkaline phosphatase activity when compared to
      the CFU-OB from their wild-type control littermates. These studies demonstrate
      that the VDR attenuates osteoblast differentiation in vitro and suggest that
      other endocrine and paracrine factors modulate the effect of the VDR on
      osteoblast differentiation in vivo.

PMID- 15517599
TI  - Serine/threonine/tyrosine phosphorylation of the LHX3 LIM-homeodomain
      transcription factor.
AB  - LHX3 is a LIM homeodomain transcription factor with essential roles in pituitary
      and motor neuron development in mammals. Patients with mutations in the LHX3 gene
      have combined pituitary hormone deficiency and other symptoms. In this study, we
      show that the LHX3 protein can be modified post-translationally by
      phosphorylation. LHX3 can serve as a substrate for protein kinase C and casein
      kinase II. Overexpression of these kinases reduces the transcriptional capacity
      of LHX3 to activate target genes. Following exposure of LHX3 to cellular kinases,
      mass spectrometry was used to map the phosphorylation of five amino acid residues
      within the human LHX3a isoform. Two phosphorylated residues (threonine 63 and
      serine 71) lie within the first LIM domain of the protein. Three other modified
      amino acids (tyrosine 227, serine 234, and serine 238) are located in the
      carboxyl terminus. Targeted replacement of these amino acids with non-modifiable
      residues significantly reduced the ability of LHX3 to activate both synthetic and
      pituitary hormone reporter genes. However, the amino acid replacements did not
      significantly affect the capability of LHX3 to interact with the NLI, PIT1, and
      MRG1 partner proteins, or its ability to bind to a high affinity DNA site. In
      conclusion, we have identified unique amino acids within LHX3 that are important
      for its transcriptional activity and are phosphorylated.

PMID- 15517601
TI  - Diagnostics for the exponential normal growth curve model.
AB  - The exponential normal regression model provides a flexible parametric approach
      to constructing growth charts or centile curves. We develop diagnostics for this
      model, with a special emphasis towards assessing the impact of individual cases
      on estimated centile curves. We also propose a standardized score residual that
      assesses the fit of individual cases to the location, scale, and skewness
      functions, respectively. An application of the proposed diagnostics is presented.

PMID- 15517602
TI  - High affinity leptin receptors are present in human mesenchymal stem cells (MSCs)
      derived from control and osteoporotic donors.
AB  - There are disparate observations on central and peripheral effects of leptin, but
      several studies consistently support its role as a link between fat and bone.
      Bone marrow stroma contains mesenchymal stem cells (MSCs), which differentiate
      into osteoblasts and adipocytes, among others. In this study we assessed the
      expression of leptin receptors protein in MSCs from control and osteoporotic
      postmenopausal donors and their change during osteogenic and adipogenic
      differentiation. Also, we assessed the effects of leptin on osteogenic and
      adipogenic differentiation of these cells. We demonstrated high affinity leptin
      binding (KD = 0.36 +/- 0.02 nM) in both types of cells. Binding was very low
      under basal, but increased significantly (2-3 times) through osteogenic and
      adipogenic differentiation. Osteoporotic MSCs showed lower leptin binding
      capacity than control cells at an early osteogenic and adipogenic differentiation
      time, which could restrict cell sensitivity to the protective action of leptin.
      In this regard, we observed that leptin significantly inhibited adipocyte
      differentiation in control but not in osteoporotic MSCs, while it exerted a low
      stimulatory effect on calcium deposition (10%-20%) in both types of MSCs cells.
      In summary, we report the presence of high affinity leptin receptors on control
      and osteoporotic MSCs, which were modified distinctly by osteogenic and
      adipogenic stimulation and a direct and distinct effect of leptin on both type of
      cells.

PMID- 15517606
TI  - Reconstitution of anti-HIV effector functions of primary human CD8 T lymphocytes
      by transfer of HIV-specific alphabeta TCR genes.
AB  - We redirected the antigen specificity of primary human CD8 T cells by retrovirus
      mediated transduction of genes encoding alphabeta TCR specific to HIV-1 Pol
      protein. A large polyclonal population of TCR-transduced CD8 T cells showed
      substantial cytotoxic and cytokine production activities toward target cells
      either pulsed with the peptide or infected with HIV-1, and their functional
      activities were comparable to those of the parental CTL clone. Peptide fine
      specificity and promiscuous recognition of HLA class I supertypes of the parental
      CTL clone were also preserved in the TCR-transduced cells. There were no signs of
      allogeneic responses in these cells, although hybrid TCR dimers consisting of
      transduced TCR and endogenous TCR were suspected to have been formed in these
      cells, as the effect of transgene expression on the surface expression of the
      desired TCR was limited. Moreover, the TCR-transduced cells showed potent
      inhibitory activity against HIV-1 replication in vitro, although the differential
      surface expression of the desired TCR resulted in differential functional avidity
      of individual TCR-transduced cells toward the peptide-pulsed target cells. These
      data suggest that the reconstitution of HIV-specific immunoreactive T cells
      engineered by genetic transfer of HIV-specific TCR is a potential alternative to
      immunotherapeutic applications against HIV infections.

PMID- 15517607
TI  - Restoration of C1q levels by bone marrow transplantation attenuates autoimmune
      disease associated with C1q deficiency in mice.
AB  - C1q deficiency in both humans and mice is strongly associated with autoimmunity.
      We have previously shown that bone marrow transplantation (BMT) restored C1q
      levels in C1q-deficient (C1qa(-/-)) mice. Here, we studied the effect of BMT on
      autoimmunity in C1qa(-/-) mice. Following irradiation, young C1qa(-/-) or wild
      type MRL/Mp mice received bone marrow cells (BMC) from strain-matched wild-type
      or C1qa(-/-) animals. C1q levels increased rapidly when C1qa(-/-) mice received
      BMC from wild-type mice. Conversely, they decreased slowly in wild-type mice
      transplanted with C1qa(-/-) BMC. C1qa(-/-) animals transplanted with C1qa(-/-)
      BMC demonstrated accelerated disease when compared with wild-type mice given wild
      type BMC. In contrast, a significant delay in the development of autoantibodies
      and glomerulonephritis was observed in C1qa(-/-) mice reconstituted with wild
      type BMC, and the impaired clearance of apoptotic cells, previously described in
      C1qa(-/-) mice, was rectified. Moreover, the autoimmune disease was accelerated
      in wild-type mice given C1qa(-/-) BMC compared to animals transplanted with wild
      type cells. These results provide supporting evidence that BMT may be a
      therapeutic option in the treatment of autoimmunity associated with human C1q
      deficiency.

PMID- 15517608
TI  - Activation of human neonatal monocyte-derived dendritic cells by
      lipopolysaccharide down-regulates birch allergen-induced Th2 differentiation.
AB  - Epidemiological studies describe an inverse association between the level of
      environmental endotoxin exposure during infancy and the prevalence of allergic
      disease in children. To study the effect of lipopolysaccharide (LPS) and
      lipopeptide Pam3Cys signaling via Toll-like receptor (TLR)4 and TLR2 on dendritic
      cells (DC), respectively, on birch allergen-induced T cell differentiation, cord
      blood monocyte-derived DC were exposed to birch allergen extract alone or in
      combination with LPS or Pam3Cys and thereafter co-cultured with naive autologous
      T cells. We demonstrate that birch allergen alone induced high levels of IL-13
      from neonatal T cells, whereas the production of IL-5 and IFN-gamma was modest.
      Stimulation of DC with birch allergen together with LPS but not Pam3Cys resulted
      in a decreased IL-13 production by T cells compared to birch allergen alone.
      Furthermore, birch allergen together with LPS induced increased up-regulation of
      activation markers expressed on the surface and production of cytokines from DC
      relative to stimulation with birch allergen alone. Finally, birch allergen
      partially suppressed both LPS- and Pam3Cys-induced DC maturation. Our results
      indicate that concomitant TLR4 stimulation during the initial phase of immune
      activation to birch allergen in infants may inhibit the development of a T helper
      2-type response.

PMID- 15517609
TI  - Role of C-C chemokine receptors 1 and 5 and CCL3/macrophage inflammatory protein
      1alpha in the cutaneous Arthus reaction: possible attenuation of their inhibitory
      effects by compensatory chemokine production.
AB  - The deposition of immune complexes induces an acute inflammatory response with
      tissue injury. Immune complex-induced tissue injury is mediated by inflammatory
      cell infiltration that is highly regulated by multiple chemokines. To assess the
      role of the chemokine receptors CCR1 and CCR5, and a ligand for these receptors
      CCL3/macrophage inflammatory protein-1alpha, in this pathogenic process, the
      reverse passive cutaneous Arthus reaction was induced in mice lacking CCR1, CCR5,
      or CCL3. Edema was significantly attenuated in CCR1-deficient (CCR1(-/-)) and
      CCL3(-/-) mice but not CCR5(-/-) mice, compared with wild-type mice. Numbers of
      infiltrating neutrophils and mast cells were reduced in CCL3(-/-) and CCR1(-/-)
      mice, respectively, compared with wild-type mice. CCR1 and CCR5 were expressed on
      neutrophils and mast cells. Remarkably, the intradermal mRNA expression of
      CCL5/RANTES, another ligand for CCR1 and CCR5, was increased in CCR5(-/-) and
      CCL3(-/-) mice, compared with wild-type mice, while the cutaneous CCL3 mRNA
      expression was augmented in CCR1(-/-) and CCR5(-/-) mice. These results indicate
      that CCR1, CCR5, and CCL3 cooperatively contribute to the cutaneous Arthus
      reaction, and also suggest that enhanced expression of CCL3 and CCL5 compensates
      for the loss of CCR1, CCR5, and CCL3 in the reaction.

PMID- 15517610
TI  - CC chemokine receptor 2 regulates leukocyte recruitment and IL-10 production
      during acute polymicrobial sepsis.
AB  - Chemokine receptors are important for recruiting leukocytes to sites of infection
      and may contribute to immune cell activation. The present study investigated the
      role of the chemokine receptor CCR2 in polymicrobial septic peritonitis. The
      results showed that peritoneal production of the CCR2 ligands CCL2 and CCL12 in
      septic mice was largely independent of the common Toll-like receptor signaling
      adaptor MyD88. Antibody blockade of CCR2 reduced the recruitment of macrophages
      and neutrophils to the infected peritoneal cavities of both wild-type and MyD88
      deficient mice, suggesting that CCR2 engagement contributes to the MyD88
      independent cellular response against polymicrobial septic peritonitis. Notably,
      administration of blocking CCR2 antibodies markedly increased local and systemic
      IL-10 levels in septic wild-type mice, whereas IL-10 was not detected in MyD88
      deficient mice irrespective of whether CCR2 was blocked or not. Inhibition of
      CCR2 directly augmented Toll-like receptor-induced IL-10, but not TNF and IL-6,
      production of macrophages in vitro. Concomitant with enhanced IL-10 production,
      CCR2 blockade caused impaired bacterial clearance and aggravated kidney injury in
      wild-type, but not MyD88-null mice. These results indicate that CCR2 engagement
      modulates the innate immune response to polymicrobial septic peritonitis by both
      MyD88-dependent and -independent processes and suggest that a major function of
      CCR2 in sepsis is to attenuate IL-10 production and IL-10-mediated suppression of
      host defense.

PMID- 15517611
TI  - Defective up-regulation of CD49d in final maturation of NOD mouse macrophages.
AB  - Macrophages are potent regulators of both innate and adaptive immunity. They play
      a central role in the development of autoimmune diabetes and are among the first
      cells to appear in peri-islet infiltrates of NOD mice that spontaneously develop
      diabetes. Since efficient adhesion and migration are crucial for proper
      macrophage trafficking, we examined the migration and fibronectin (FN) adhesion
      capacity of NOD macrophages, as well as the regulation and expression of the FN
      receptors alpha4beta1 and alpha5beta1. When compared to macrophages from control
      strains, resident NOD macrophages showed a reduced ability to adhere to and
      migrate on FN, a delayed clearance following peritoneal inflammation, and
      substantially lower expression levels of the alpha4beta1 integrin alpha chain,
      CD49d. NOD bone marrow-derived macrophages were specifically defective in the LPS
      induced increase in CD49d expression. Moreover, the mitogen-activated protein
      kinase extracellular signal-regulated kinase-1/2 negatively regulated macrophage
      CD49d expression and strongly suppressed its expression in NOD macrophages. The
      data presented herein indicate that the LPS-activated signaling cascade plays a
      critical role in CD49d expression of macrophages. Mature NOD macrophages are
      characterized by decreased CD49d expression and show defective CD49d-mediated
      adhesion to FN.

PMID- 15517612
TI  - Activating CD94:NKG2C and inhibitory CD94:NKG2A receptors are expressed by
      distinct subsets of committed CD8+ TCR alphabeta lymphocytes.
AB  - A subset of CD8(+) T cells express the natural killer cell receptors CD94:NKG2A
      or CD94:NKG2C. We found that although many CD8(+) T cells transcribe CD94 and
      NKG2C, expression of a functional CD94:NKG2C receptor is restricted to highly
      differentiated effector cells. CD94:NKG2A is expressed by a different subset
      consisting of CCR7(+) memory cells and CCR7(-) effector cells. Since NKG2A can
      only be induced on naive CD8(+) T cells while CD94(-) memory cells are
      refractory, it is likely that commitment to the CD94:NKG2A(+) subset occurs
      during the first encounter with antigen. CCR7(+)CD94:NKG2A(+) T cells recirculate
      through lymph nodes where upon activation, they produce large quantities of IFN
      gamma. These cells occur as a separate CD94:NKG2A(+) T cell lineage with a
      distinct TCR repertoire that differs from that of the other CD8(+)CD94(-) T cells
      activated in situ.

PMID- 15517613
TI  - Microbial colonization induces oligoclonal expansions of intraepithelial CD8 T
      cells in the gut.
AB  - Two populations of CD8(+) IEL generally express restricted, but apparently random
      and non-overlapping TCR repertoires. Previous studies in mice suggested that this
      could be explained by a dual origin of CD8(+) IEL, i.e. that CD8alphabeta(+) IEL
      derive from a few peripheral CD8(+) T cell lymphoblasts stimulated by microbial
      antigens in gut-associated lymphoid tissue, whereas CD8alphaalpha(+) IEL descend
      from an inefficient intestinal maturation pathway. We show here that the gut
      mucosa, instead, becomes seeded with surprisingly broad and generally non
      overlapping CD8 IEL repertoires and that oligoclonality is induced locally after
      microbial colonization. In germ-free (GF) rats, both CD8alphabeta(+) and
      CD8alphaalpha(+) IEL displayed surprisingly diverse TCR Vbeta repertoires,
      although beta-chain diversity tended to be somewhat restricted in the
      CD8alphaalpha(+) subset. CDR3 length displays in individual Vbeta-Cbeta and Vbeta
      Jbeta combinations generally revealed polyclonal distributions over 6-11
      different lengths, similar to CD8(+) lymph node T cells, and CDR3beta sequencing
      provided further documentation of repertoire diversity. By contrast, in ex-GF
      rats colonized with normal commensal microflora, both CD8alphabeta(+) and
      CD8alphaalpha(+) IEL displayed oligoclonal CDR3 length distributions for most of
      the Vbeta genes analyzed. Our data suggest that microbial colonization induces
      apparently random clonal expansions of CD8alphabeta(+) and CD8alphaalpha(+) IEL
      locally in the gut.

PMID- 15517614
TI  - Antagonist anti-human CD40 antibody inhibits germinal center formation in
      cynomolgus monkeys.
AB  - Interactions between CD40 on APC and CD154 (CD40L) expressed by activated CD4(+)
      T cells are crucially involved in formation and function of germinal centers
      (GC), but mechanistic insight into these interactions remains limited. Functional
      studies have mostly been restricted to experimental immunization of young-adult
      inbred SPF rodents that are often genetically manipulated, while studies in
      humans disallow in vivo manipulation. Therefore, we asked whether a functional
      antagonist of CD40 interferes with natural GC formation in adult cynomolgus
      monkeys (Macaca fascicularis) exposed to the environmental antigens of their
      conventional housing in captivity. Animals were treated with different doses of a
      unique chimeric antagonist anti-CD40 mAb (ch5D12) and analyzed 1 week or 7 weeks
      after last injection. Detailed in situ analysis showed that high-dose anti-CD40
      treatment increased the ratio of primary over secondary follicles compared to PBS
      or low-dose treatment, indicative of impairment of the CG reaction. This
      impairment was reversible since recovery animals, except those with residual anti
      CD40 levels, had normalized ratios. Anti-CD40 treatment was associated with
      decreased antibody production and increased numbers of apoptotic cells in GC.
      These data demonstrate that CD40-CD154 interactions are pivotal in physiological
      GC formation in primates responding to environmental antigens, and they support
      immunotherapeutic strategies using antagonist anti-CD40.

PMID- 15517615
TI  - Intraocular injection of tamoxifen-loaded nanoparticles: a new treatment of
      experimental autoimmune uveoretinitis.
AB  - In this study, we tested the efficiency of an intravitreal injection of
      tamoxifen, a non-steroidal estrogen receptor modulator, in retinal soluble
      antigen (S-Ag)-induced experimental autoimmune uveoretinitis (EAU). To increase
      the bioavailability of tamoxifen, we incorporated tamoxifen into polyethylene
      glycol (PEG)-coated nanoparticles (NP-PEG-TAM). The localization of the
      nanoparticles within the eye was investigated using fluorescent-labeled PEG
      coated nanoparticles after injection into the vitreous cavity of rats with EAU.
      Some nanoparticles were distributed extracellularly throughout the ocular
      tissues, others were concentrated in resident ocular cells and in infiltrating
      macrophages. Whereas the injection of free tamoxifen did not alter the course of
      EAU, injection of NP-PEG-TAM performed 1-2 days before the expected onset of the
      disease in controls resulted in significant inhibition of EAU. NP-PEG-TAM
      injection significantly reduced EAU compared to injection of NP-PEG-TAM with
      17beta-estradiol (E2), suggesting that tamoxifen is acting as a partial
      antagonist to E2. Diminished infiltration by MHC class II(+) inflammatory cells
      and low expression of TNF-alpha, IL-1beta, and RANTES mRNA were noted in eyes of
      NP-PEG-TAM-treated rats. Intravitreal injection of NP-PEG-TAM decreased S-Ag
      lymphocyte proliferation, IFN-gamma production by inguinal lymph node cells, and
      specific delayed-type hypersensitivity indicative of a reduced Th1-type response.
      It increased the anti-S-Ag IgG1 isotype indicating an antibody class switch to
      Th2 response. These data suggest that NP-PEG-TAM inhibition of EAU could result
      from a form of immune deviation. Tamoxifen-loaded nanoparticles may represent a
      new option for the treatment of experimental uveitis.

PMID- 15517616
TI  - The pathogenesis of neuropsychiatric manifestations in systemic lupus
      erythematosus: a disease in search of autoantibodies, or autoantibodies in search
      of a disease?

PMID- 15517617
TI  - Anticardiolipin test and the antiphospholipid (Hughes) syndrome: 20 years and
      counting!

PMID- 15517618
TI  - Nonhuman primate seronegative arthritis: probability values for valuable science
      in a case report.

PMID- 15517619
TI  - Continuous passive motion: from origination to research to clinical applications.

PMID- 15517620
TI  - Wnt1 inducible signaling pathway protein-3 regulation and microsatellite
      structure in arthritis.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) synovial tissue expresses several embryonic
      gene families, including wingless (wnt) and their receptors, frizzled (fz). The
      Wnt proteins, including Wnt-1, activate the Wnt inducible signaling pathway
      proteins (WISP), which are members of the CCN family that regulate cell growth
      and differentiation. WISP3 is of particular interest because it contains a
      microsatellite region in its coding region that is susceptible to frameshift
      mutations and leads to a truncated protein. To investigate the contribution of
      WISP3 to synovial inflammation, we evaluated its expression and regulation in
      arthritis. METHODS: mRNA and protein expression of WISP3 were determined by
      quantitative real-time polymerase chain reaction (PCR) and Western blot analysis,
      respectively. For mutation analysis, PCR product amplified from genomic DNA of
      synovial tissue and cultured fibroblast-like synoviocytes (FLS) was subcloned and
      sequenced. RESULTS: WISP3 mRNA is expressed in synovial tissue, but is 11-fold
      higher in RA than osteoarthritis (OA) or normal samples. Surprisingly, WISP3
      protein levels are similar in RA, OA, and normal synovium samples.
      Immunohistochemistry of synovial tissue reveals that WISP3 protein is located
      primarily in the synovial intimal lining. WISP3 mRNA expression is also 6-fold
      higher in RA FLS compared with OA FLS and 50-fold higher in RA than in normal
      FLS. When RA FLS are stimulated with interleukin 1 or tumor necrosis factor-a,
      WISP3 mRNA is significantly increased. The cytokines also increase WISP3 mRNA in
      OA FLS, but the maximal level in stimulated OA FLS is still less than medium
      treated RA FLS. Mutation analysis in the coding region microsatellite of the
      WISP3 gene in RA and OA synovium and FLS shows a limited number of insertion and
      deletion mutations. CONCLUSION: WISP3 gene expression is higher in RA synovium
      and FLS compared with OA and normal synovial tissue and is further induced by
      proinflammatory cytokines in vitro. Protein levels are not increased, indicating
      discoordinate regulation of WISP3 protein and mRNA. Although functionally
      relevant mutations were observed in genomic DNA, they were noted in both OA and
      RA samples.

PMID- 15517621
TI  - Fatigue, rheumatoid arthritis, and anti-tumor necrosis factor therapy: an
      investigation in 24,831 patients.
AB  - OBJECTIVE: Fatigue is a common and distressing symptom in patients with
      rheumatoid arthritis (RA) and other rheumatic diseases. Reports have suggested
      profound improvements in fatigue after onset of anti-tumor necrosis factor-alpha
      (anti-TNF) therapy. In addition, physician and patient groups now identify
      fatigue as a very important symptom. However, data to support these observations
      are lacking. We evaluate the importance of fatigue in relation to other measures
      of clinical status, describe predictors of fatigue, and investigate fatigue
      levels in patients treated with anti-TNF therapy. METHODS: A total of 852
      patients participated in a symptom-importance preference study. Additional
      analyses of fatigue and other clinical status variables were performed in up to
      21,016 patients with RA and 3815 patients with osteoarthritis (OA) participating
      in the National Data Bank for Rheumatic Diseases. RESULTS: In ranking studies of
      the relative importance of fatigue compared with function, pain, cognition,
      gastrointestinal symptoms, and sleep, 8.0% of patients ranked fatigue as the most
      important variable, compared with 32.1% for function and 21.5% for pain.
      Multivariable studies of clinical change over 6 months found that changes in
      fatigue were weakly associated with changes in health status, in
      contradistinction to results for pain, function, and depression. Fatigue levels
      and fatigue predictors were similar in RA and OA patients. RA patients treated
      with anti-TNF therapy did not have lower fatigue scores compared with those not
      treated with this type of therapy. CONCLUSION: Among RA patient self-report
      measures, fatigue is not ranked as important as functional disability, pain, or
      depression by most patients. This relative ranking is confirmed by examination of
      clinical improvement data. Fatigue levels and predictors of fatigue are
      essentially the same in RA and OA. Although anti-TNF therapy lowers fatigue
      levels, there is no evidence that this effect is greater for anti-TNF therapy
      than for other RA treatments.

PMID- 15517622
TI  - Efficacy and safety of willow bark extract in the treatment of osteoarthritis and
      rheumatoid arthritis: results of 2 randomized double-blind controlled trials.
AB  - OBJECTIVE: To investigate the efficacy and safety of a standardized willow bark
      extract in patients with osteoarthritis (OA) and rheumatoid arthritis (RA).
      METHODS: We studied 127 outpatients with hip or knee OA and a WOMAC pain score of
      at least 30 mm and 26 outpatients with active RA in 2 randomized, controlled,
      double-blind trials with followup for 6 weeks. OA trial: Patients were randomized
      to receive willow bark extract, corresponding to 240 mg of salicin/day,
      diclofenac 100 mg/day, or placebo (n = 43, 43, and 41, respectively). Main
      outcome measure was the pain subscore of the WOMAC OA Index. RA trial: Patients
      were randomized to receive willow bark extract, corresponding to 240 mg
      salicin/day (n = 13) or placebo (n = 13). Main outcome measure was the patient's
      assessment of pain rated on a 100 mm visual analog scale (VAS). RESULTS: OA
      trial: WOMAC pain scores decreased by 8 mm (17%) in the willow bark group and by
      23 mm (47%) in the diclofenac group, compared with 5 mm (10%) in the placebo
      group. The difference between willow bark extract and placebo was not
      statistically significant (-2.8 mm; 95% CI -12.1 to 6.4 mm; p = 0.55, ANCOVA),
      but the difference between diclofenac and placebo was highly significant (-18.0
      mm; 95% CI -27.2 to -8.8 mm; p = 0.0002, ANCOVA). RA trial: The mean reduction of
      pain on the VAS was -8 mm (15%) in the willow bark group compared with -2 mm (4%)
      in the placebo group. The difference was not statistically significant (estimated
      difference -0.8 mm; 95% CI -20.9 to 19.3 mm; p = 0.93, ANCOVA). CONCLUSION: The
      OA study suggested that the willow bark extract showed no relevant efficacy in
      patients with OA. Similarly, the RA trial did not indicate efficacy of this
      extract in patients with RA.

PMID- 15517623
TI  - Effects of Prosorba column apheresis in patients with chronic refractory
      rheumatoid arthritis.
AB  - OBJECTIVE: Since the approval of Prosorba column apheresis therapy (PCT) for
      rheumatoid arthritis (RA) in 1999 there have been multiple requests for
      additional information on the response rate of PCT used commercially in
      rheumatology practice settings. METHODS: Data were collected in a
      noninterventional prospective fashion on patients with RA who qualified for the
      PCT treatment per the package insert. There were 91 patients who completed the 12
      prescribed treatments. There was no washout of other drugs [i.e., disease
      modifying antirheumatic drugs (DMARD), biologics]. An initial baseline assessment
      was performed prior to first treatment and then up to 4 additional assessments
      were performed at Weeks 9, 16, 20, and 24. Criteria for ACR20 were noted in order
      to assess response rate, and commercial adverse event reporting was used to
      record serious/unanticipated adverse events. RESULTS: There was a response rate
      of 53.8% (measured as ACR20 response or better) in these patients with previously
      refractory RA. The individual criteria showed a much greater improvement than
      reflected by ACR20; for example, this response included a 52% improvement in
      joint tenderness, 40% improvement in swelling, 42% improvement in patient's pain,
      38% improvement in patient's global response, and 48% improvement in physician's
      global scores (76% of responders had measured ACR20 by Week 16 and 100% by Week
      24). The actual measurement of an ACR response generally occurred during
      assessments at Week 16; however, most patients who respond will state they felt
      improvement some time between Weeks 8 and 12. There were no assessments between
      Weeks 9 and 16 so the actual week of improvement could not be identified by ACR
      criteria. Some patients stated that they felt improvement began closer to the 6th
      week. Most responders were concurrently taking biologics or DMARD, e.g.,
      methotrexate and etanercept, despite previously inadequate RA response to those
      medications. CONCLUSION: This postmarketing study of PCT used commercially in 59
      rheumatology practice settings supports the safety and efficacy of this treatment
      regime in selected patients with RA and compares favorably with the initial sham
      controlled clinical trial. PCT is a relatively underutilized choice for the
      management of active, aggressive RA.

PMID- 15517624
TI  - Thoracic surgical procedures in patients with rheumatoid arthritis.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is associated with a variety of
      pleuropulmonary manifestations, some of which require surgical intervention. We
      investigated the spectrum of indications and results, as well as outcome
      associated with thoracic surgical procedures in rheumatoid patients. METHODS:
      Identification and retrospective review of medical records of 100 patients with
      RA at a tertiary-referral medical center undergoing thoracic surgical procedures
      over a 24-year period from January 1, 1976, to December 31, 1999. RESULTS: Sixty
      four patients underwent surgical lung biopsy for localized lung lesions, 57 of
      which were nodules or masses; 24 lesions proved to be malignant. Surgical lung
      biopsy was undertaken in 40 patients for diffuse interstitial lung disease, 4
      cases of which were found to be infectious. Five other patients underwent surgery
      for pleural disease, 3 of which proved to be benign pleuritis. CONCLUSION:
      Patients with rheumatoid disease undergo thoracic surgical procedures for a
      variety of indications, including benign and malignant localized lesions and
      pleural disease as well as diffuse parenchymal lung disease. The overall in
      hospital mortality rate was low. However, the subgroup with diffuse interstitial
      lung disease was found to have a 20% in-hospital death rate following surgical
      lung biopsy.

PMID- 15517625
TI  - Autoimmune response to proteins of proliferating cell nuclear antigen
      multiprotein complexes in patients with connective tissue diseases.
AB  - OBJECTIVE: To analyze the autoimmune response to the proliferating cell nuclear
      antigen (PCNA) multiprotein complex in patients with connective tissue diseases
      (CTD). METHODS: The PCNA complex was purified by affinity chromatography using
      anti-PCNA monoclonal antibodies. Then 196 serum samples from patients with
      systemic lupus erythematosus (SLE) and 82 from patients with other CTD were
      tested for reactivity with the complex by immunoblotting. RESULTS: Of 196 SLE
      sera, 61 (31%) reacted with at least one component of the PCNA complex, and most
      reactive sera contained autoantibodies to several components of the complex.
      Autoantibodies to PCNA complex were less common in patients with other CTD, and
      most of their sera reacted only with one or a few proteins in the complex. Two
      out of 20 scleroderma sera reactive with 100, 85, and 70 kDa proteins in the PCNA
      complex also had autoantibodies to topoisomerase I (topo I) antibodies, which is
      an element of the complex. These findings suggest that the autoimmune response to
      the PCNA complex was specific for SLE. Anti-PCNA complex antibodies were
      associated with an increased serum level of PCNA detected by ELISA. The spreading
      of the autoimmune response to the elements of the complex was observed in
      parallel with the increased serum PCNA level when a series of sera from a lupus
      patient were tested longitudinally. In addition, anti-PCNA complex antibodies
      were significantly correlated with lupus erythematosus cells. CONCLUSION: The
      "antigen-drive" system may play a crucial role in inducing the autoimmune
      response to the PCNA complex in patients with SLE.

PMID- 15517626
TI  - Association of reduced CD4 T cell responses specific to varicella zoster virus
      with high incidence of herpes zoster in patients with systemic lupus
      erythematosus.
AB  - OBJECTIVE: To examine whether the high incidence of herpes zoster in patients
      with systemic lupus erythematosus (SLE) is associated with the frequency of
      memory T cells specific to varicella zoster virus (VZV). METHODS: Whole blood
      samples from 47 subjects [24 patients with SLE, 11 with rheumatoid arthritis (RA)
      as a disease control, and 12 healthy negative controls] were stimulated with VZV
      antigen, stained for surface CD4 and CD8 and intracellularly stained for the
      cytokines interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha),
      interleukin 4 (IL-4), and IL-10, followed by flow cytometry analyses.
      Correlations of VZV-specific T cell frequencies with the clinical status of
      patients were analyzed. RESULTS: Percentage of IFN-gamma-positive CD4 T cells was
      significantly lower in patients with SLE (0.043 +/- 0.009%) than in RA (0.102 +/-
      0.019%) and healthy controls (0.126 +/- 0.025%) upon VZV stimulation. A similar
      pattern was seen in TNF-alpha-positive CD4 T cell responses. These low
      frequencies of VZV-specific CD4 T cells in patients with SLE were significantly
      related with disease activity (r = -0.435, p = 0.043). CONCLUSION: These data
      suggest that the high incidence of herpes zoster in patients with SLE was related
      to the intrinsic defects in controlling VZV reactivation, and thus VZV-specific
      CD4 T cell frequency could be another practical risk factor of herpes zoster in
      patients with SLE.

PMID- 15517627
TI  - Neuropsychiatric events in systemic lupus erythematosus: attribution and clinical
      significance.
AB  - OBJECTIVE: To describe the range and attribution of neuropsychiatric (NP) disease
      in an unselected cohort of patients with systemic lupus erythematosus (SLE) and
      to examine the association with cumulative organ damage, medication use, and
      quality of life. METHODS: One hundred eleven patients with SLE in a single
      referral center were studied. NP syndromes were defined using the American
      College of Rheumatology (ACR) nomenclature and case definitions. Overall disease
      activity was measured by the SLE Disease Activity Index (SLEDAI); cumulative
      organ damage was determined by the ACR/SLICC damage index; and quality of life by
      the SF-36. RESULTS: Patients' mean age was 44.7 years, 87% were female, and 92%
      were Caucasian. The mean (+/- SE) disease duration was 10.1 +/- 0.7 years. A
      total of 74 NP events were identified in 41 of 111 (37%) patients. Thirteen of
      the 19 ACR NP syndromes were identified and 2 or more NP manifestations occurred
      in 56% of patients. Central nervous system manifestations accounted for 92% of
      the events compared to involvement of the peripheral nervous system in 8%. Thirty
      five (47%) of these events were attributed entirely to SLE, 30 (41%) were
      attributed exclusively to non-SLE factors, and in the remaining 9 events (12%)
      both SLE and non-SLE factors were felt to be contributory. Cumulative organ
      damage was higher in patients with NP disease, although this was not
      statistically significant and they were more likely to have received prednisone
      or immunosuppressive drugs (p < 0.05). Patients with NP disease reported more
      fatigue (p < 0.05) and had significantly lower scores on 7 of 8 subscales of the
      SF-36 (p < 0.05). These associations were found regardless of the attribution of
      NP disease. In contrast, the occurrence of renal disease in the same cohort of
      patients was not associated with lower SF-36 scores or fatigue. CONCLUSION: In
      patients with SLE, NP disease has diverse manifestations and can be attributed to
      lupus in roughly half of the cases. The occurrence of NP disease is associated
      with more frequent use of corticosteroids and immunosuppressive drugs. In
      contrast to other serious manifestations of SLE, such as renal disease, NP
      disease is associated with a significant reduction in quality of life.

PMID- 15517628
TI  - Endothelial nitric oxide synthase gene polymorphism is associated with systemic
      lupus erythematosus.
AB  - OBJECTIVE: In systemic lupus erythematosus (SLE), endothelial nitric oxide
      synthase (eNOS) gene locus has been found to be suggestive of linkage with
      disease, nitric oxide (NO) is produced in significant amounts, and endothelial
      cell dysfunction is observed. eNOS gene polymorphism may affect both the
      synthesis of eNOS protein and its enzymatic activity. We examined the influence
      of eNOS gene polymorphisms on susceptibility to SLE. METHODS: Genomic DNA from 88
      Northwestern Colombian women with SLE, as well as 199 controls matched for sex,
      age, and ethnicity, was genotyped for the -786T -- > C polymorphism in the
      promoter region, the intron 4 variable number of tandem repeats, and the
      Glu298Asp polymorphism in exon 7 of the eNOS gene by polymerase chain reaction
      and restriction fragment length polymorphism techniques. Haplotype and allele
      frequency comparisons, a Hardy-Weinberg equilibrium test, and linkage
      disequilibrium (LD) analysis were performed. RESULTS: The intron 4b allele was
      associated with SLE (OR 2.2, 95% CI 1.29-3.60, pc = 0.005) as was the 4bb
      genotype (OR 2.9, 95% CI 1.61-5.33, pc = 0.0009), while the 4a allele was
      protective (OR 0.4, 95% CI 0.26-0.76, pc = 0.005), as was the 4ab genotype (OR
      0.29, 95% CI 0.15-0.56, pc < 0.0001). In controls, all loci were in linkage
      disequilibrium (p < 0.02). In patients, intron 4 was in Hardy-Weinberg
      disequilibrium, due to an excess of homozygotes (p = 0.01). CONCLUSION: eNOS
      polymorphism influences SLE predisposition. Since intron 4bb genotype is
      responsible for higher levels of eNOS synthesis and intron 4 ab genotype is
      associated with lower synthesis, our results might provide insight into the
      elevated levels of NO observed in SLE patients.

PMID- 15517630
TI  - Immunoglobulin KM and GM gene polymorphisms modify the clinical presentation of
      primary Sjogren's syndrome.
AB  - OBJECTIVE: To investigate whether polymorphism of immunoglobulin (Ig) genes
      affects susceptibility to or severity of primary Sjogren's syndrome (pSS).
      METHODS: Ig gene kappa (KM) and gamma (GM) polymorphisms were analyzed by a
      polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP)
      based method in 65 Finnish Caucasian patients with pSS and in 66 healthy controls
      matched for sex, ethnic origin, and area of residence. Clinical and immunological
      data on the pSS patients were analyzed in relation to Ig genotypes. RESULTS: The
      genotype frequencies of Ig KM and GM genes did not differ between pSS patients
      and controls. Anti-SSB antibodies were encountered significantly more frequently
      in pSS patients carrying the KM1 allele than in those without (100% vs 48%, p =
      0.016). The pSS patients with the KM1 allele had several signs of immunologically
      active disease: they had significantly higher erythrocyte sedimentation rate,
      serum IgA, serum beta2-microglobulin (beta2-m), and plasma IgG1 concentrations
      than patients without this allele. The pSS patients carrying the GM z allele had
      a milder form of pSS than those without this determinant. They had less severe
      labial salivary gland histological findings (grade 3-4 in 60% vs 93%, p = 0.004)
      and lower plasma IgG3 and serum beta2-m concentrations than those without GM z
      allele. CONCLUSIONS: Ig KM and GM genes do not contribute to susceptibility to
      pSS. The Ig KM1 allele is associated with several markers of immunologically
      active disease, whereas the Ig GM z allele is associated with milder pSS.

PMID- 15517629
TI  - Patients with antibodies to both PmScl and dsDNA.
AB  - OBJECTIVE: To determine the significance of dsDNA antibodies in patients with
      antibodies to PmScl. METHODS: All patients testing positive for PmScl and/or
      dsDNA antibodies at an academic medical center between 1977 and 2002 were
      identified. Charts for the PmScl-positive patients were reviewed for
      manifestations of lupus, scleroderma, or polymyositis/dermatomyositis. Patients
      with antibodies to dsDNA were matched to each of the double-positive
      PmScl+/dsDNA+ patients on the basis of sex, race, age, and date of autoantibody
      testing. Standard classification criteria for lupus, scleroderma, and myositis
      were used (excluding dsDNA, PmScl, or antinuclear antibodies as criteria), and
      the number of subjects meeting classification criteria was recorded. RESULTS:
      Records were available for 38 out of 47 patients who were identified as PmScl
      positive. The prevalence of dsDNA antibodies in this group was 42% (16/38).
      Patients with PmScl and dsDNA antibodies had a higher prevalence of systemic
      lupus erythematosus (8/16 vs 2/22; p = 0.008) and a lower rate of scleroderma or
      myositis (1/16 vs 9/22; p = 0.025) than dsDNA-negative patients with PmScl
      antibodies. The prevalence of systemic lupus erythematosus, myositis, and
      scleroderma in patients with PmScl and dsDNA antibodies was not different from
      the prevalences of these diseases in a matched cohort of patients who were dsDNA
      positive. CONCLUSION: Antibodies to PmScl are associated with scleroderma and
      myositis when dsDNA antibodies are not present. In the presence of dsDNA
      antibodies, PmScl antibodies do not appear to have clinical relevance.

PMID- 15517631
TI  - Polyarteritis nodosa reports to the vaccine adverse event reporting system
      (VAERS): implications for assessment of suspected vaccine-provoked vasculitis.
AB  - OBJECTIVE: To examine polyarteritis nodosa (PAN) reports to the Vaccine Adverse
      Event Reporting System (VAERS) as the initial stage in investigating the
      hypothesis that vaccination can very rarely cause PAN. METHODS: We reviewed PAN
      reports submitted from 1990 through 2001 using a causal inference framework to
      evaluate the consistency of the reports' clinical details with this hypothesis.
      We also reviewed published literature relating to the hypothesized association's
      biological plausibility. RESULTS: VAERS received 25 PAN reports. Ten met our case
      definition for definite or possible PAN and had no alternative etiology for PAN
      identified. Nine of these 10 followed hepatitis B vaccine with a modal peak (4
      definite cases) in time to symptom onset 2 weeks after vaccination. However, all
      potential triggering infections were not excluded, and identification of vaccine
      antigens in clinical specimens was not attempted. Also, 14 of 25 reports were
      European, with 11 from France. All 9 French reports with a known diagnosis date
      began during 1994-97, when autoimmune and rheumatologic events following
      hepatitis B vaccine were a focus of public concern in France. CONCLUSION: While
      we identified some supportive evidence, overall, current adverse event reports do
      not support a causal link between vaccination and PAN. Appropriate prospective
      evaluation of future post-vaccination PAN cases could add to current knowledge
      with rigorous confirmation of diagnosis, appropriate testing for possible
      triggering infections including polymerase chain reaction testing for latent
      hepatitis B infection, and an attempt to link the vaccine antigen to pathology
      such as by immunohistochemical staining or immune complex identification.

PMID- 15517632
TI  - Proinflammatory cytokine profiles in sera and pathological tissues of patients
      with active untreated adult onset Still's disease.
AB  - OBJECTIVE: To investigate concentrations of proinflammatory cytokines in the sera
      and their mRNA expression in biopsy specimens of evanescent rash and synovitis
      from patients with active untreated adult onset Still's disease (AOSD). METHODS:
      We measured serum levels of interleukin 6 (IL-6), IL-8, and tumor necrosis factor
      (TNF-alpha) by immunochemiluminescence method and serum IL-18 levels by ELISA in
      50 patients with active untreated AOSD, 20 patients with active rheumatoid
      arthritis (RA), and 20 healthy controls. Multivariate analysis was used to
      evaluate the correlation between serum cytokine levels and disease activity and
      clinical features of AOSD. We also evaluated the expression of cytokine
      transcripts by real-time quantitative polymerase chain reaction in biopsy
      specimens of evanescent rash and synovitis from 12 patients with active untreated
      AOSD. RESULTS: Significantly higher levels of IL-6, IL-8, IL-18, and TNF-alpha in
      sera were found in patients with active untreated AOSD compared to healthy
      controls. Serum levels of IL-6 and IL-18 correlated well with clinical activity
      score of AOSD patients. Multiple logistic regression analysis showed that serum
      IL-6 level was a possible predictor for the occurrence of evanescent rash (p =
      0.0593), serum IL-8 level was a significant predictor of persistent arthritis,
      and serum IL-18 level predicted occurrence of liver dysfunction. The levels of
      mRNA expression of IL-6, IL-18, and IL-8 were significantly higher in the biopsy
      tissue of Still's rash from AOSD patients compared with those in controls. Levels
      of mRNA expression of IL-18, IL-8, and TNF-alpha were significantly higher in the
      synovial membranes of AOSD patients compared with those in osteoarthritis
      controls. Significantly lower levels of TNF-alpha and IL-8 were found in the sera
      and in the synovial membranes of AOSD patients compared with those in RA
      patients. AOSD patients who had a chronic articular course had significantly
      higher levels of serum IL-8 compared with those who had a monocyclic systemic
      course. CONCLUSION: Significantly higher levels of IL-6, IL-8, IL-18, and TNF
      alpha were seen in both sera and pathological tissues of patients with active
      AOSD. The associations between levels of cytokine profile and distinct clinical
      manifestations and various patterns of disease course suggest the heterogeneity
      of pathogenesis in AOSD.

PMID- 15517633
TI  - Longterm course of mixed cryoglobulinemia in patients infected with hepatitis C
      virus.
AB  - OBJECTIVE: To describe epidemiological, clinical, and immunological
      characteristics and the longterm course of persistent mixed cryoglobulinemia (MC)
      in patients infected with hepatitis C virus (HCV). METHODS: Retrospective study
      of HCV infected patients (HCV RNA positive) who had persistent positive MC, with
      2 immunochemical typings of MC carried out after 24-month minimum interval.
      RESULTS: In total, 125 patients were studied, aged 52 +/- 13 years at diagnosis
      of MC, with duration of HCV infection of 18 +/- 10 years. At entry, 60 patients
      had type II MC, 53 patients had type III, and 12 patients had the oligoclonal
      type. At the second immunochemical typing, after a mean interval of 45 +/- 20
      months, MC was type II in 72 patients, type III in 39 patients, and the
      oligoclonal type in 14 patients. The proportion of cases of MC with the same
      immunochemical type was higher among patients with type II (78%) than type III
      (59%) or oligoclonal MC (17%) (p < 0.01). The MC that changed turned more to type
      II (55.5%) than type III (29%) or the oligoclonal type (15.5%) (p = 0.0002). MC
      vasculitis (purpura, arthralgia, peripheral neuropathy, renal involvement) and
      other extrahepatic manifestations (polyarteritis nodosa, lymphoma) in 60/125
      patients was associated with advanced age (p < 0.01), a longer duration of
      infection (p < 0.05), type II MC (odds ratio = 5, p < 0.01), and a higher MC
      serum level (p < 0.01). CONCLUSION: During chronic active HCV infection, type II
      MC is more stable over time than type III and oligoclonal MC. The oligoclonal
      type appears to be an intermediate stage in the course of type III changing to
      type II MC. Symptomatic persistent HCV MC was associated with advanced age,
      longer duration of HCV infection, type II MC, and a higher MC serum level.

PMID- 15517634
TI  - Assessment of the 3-dimensional Fastrak measurement system in measuring range of
      motion in ankylosing spondylitis.
AB  - OBJECTIVE: To assess the repeatability and validity of the electromagnetic 3
      dimensional tracking system, Fastrak, in measuring cervical spine and shoulder
      movement in patients with ankylosing spondylitis (AS). METHODS: Fifty patients
      with AS had their cervical spine and shoulder movements measured on up to 3
      occasions with the Fastrak. Patients also completed disease-specific and generic
      patient assessed health instruments, and their spinal mobility was assessed by
      tape measure methods. Repeatability over 2 weeks was assessed using intraclass
      correlation coefficients (ICC). Fastrak measurements were compared between
      patients with different self-ratings of AS related health. Comparisons between
      the Fastrak measurements and patient assessed health instruments and tape
      measurements were made using Spearman correlations and multilevel modeling.
      RESULTS: Patients with AS tended to be limited in both cervical spine and
      shoulder movements. ICC were all > 0.80 (except shoulder extension, 0.75),
      indicating substantial reliability. Fastrak was able to differentiate between
      patients with a high self-rating of AS related health and those with a poorer
      rating. Cervical spine flexion and shoulder flexion and abduction were most
      strongly related to the patient assessed health instruments, although the
      shoulder movements had limited relationships with the tape measurements of spinal
      mobility. CONCLUSION: The Fastrak appears to be reliable and valid in an AS
      population. Shoulder movements tended to have a stronger relationship with the
      patient assessed health instruments than cervical spine movements. Shoulder
      movement may be more related to everyday function measured by these instruments,
      which indicates the importance of this joint in assessment of AS.

PMID- 15517635
TI  - Quantitative cytochemical evidence for local increases in bone turnover at the
      acromial enthesis of the human coracoacromial ligament.
AB  - OBJECTIVE: Enthesophytic bone outgrowths are found at many ligament attachment
      sites, and while their incidence is associated with many pathologies, the
      mechanism by which they form remains controversial. We hypothesized that changes
      in local cell behavior, provoked by mechanical alterations within the
      coracoacromial ligament (CAL), lead to acromial enthesophyte formation. We
      investigated whether cell behavior at acromial entheses is consistent with this.
      METHODS: We used quantitative enzyme cytochemistry to measure glucose 6-phosphate
      dehydrogenase (G6PD), alkaline phosphatase (ALP; osteoblastic activity), and
      tartrate-resistant acid phosphatase (TRAP; osteoclastic phenotype) activities in
      cells of the acromial attachment into the CAL in patients with rotator cuff
      tears. RESULTS: (1) Resident osteoblasts on the acromion's inferior aspect
      express elevated activity of G6PD and ALP, indicative of increases in osteogenic
      potential. (2) These activities are selectively raised at the "leading edge" of
      acromial bone CAL enthesis. (3) In contrast, distribution of TRAP-positive cells
      does not exhibit a spatial correlation with enthesis architecture. We also found
      that cells situated close to the CAL attachment into the acromion exhibited
      elevated levels of G6PD and ALP activity, but intriguingly, also showed higher
      TRAP activity than neighboring cells distant from entheses. CONCLUSION: These
      results suggest that the acromion in these patients undergoes bone accretion at
      the inferior attachment of the CAL, and that enthesial ligament cells close to
      the bone express characteristics consistent with enthesophyte formation at the
      leading edge of this bony spur's extension into the ligament.

PMID- 15517636
TI  - Prevalence of the spondyloarthritides in patients with uveitis.
AB  - OBJECTIVE: To determine the prevalence of the spondyloarthritides in patients
      with uveitis and to establish criteria for certain subtypes of this group of
      diseases. METHODS: In a university-based prospective study, we examined 433
      patients with different types of uveitis for signs of spondyloarthritides as
      defined by the classification criteria of the European Spondylarthropathy Study
      Group (ESSG). RESULTS: Forty-four of the 433 uveitis patients (36 with acute
      anterior uveitis and 8 with other types of uveitis) had spondyloarthritis
      according to the ESSG classification criteria. Nineteen of these 44 patients had
      ankylosing spondylitis (AS), 11 had undifferentiated spondyloarthritis, 9
      reactive arthritis, and 5 psoriatic arthritis. CONCLUSION: Uveitis is associated
      not only with AS and reactive arthritis, but also with undifferentiated
      spondyloarthritis and psoriatic arthritis. The ESSG criteria are helpful in
      identifying these spondyloarthritides in uveitis patients.

PMID- 15517637
TI  - Analysis of 6 genetic loci for disease susceptibility in psoriatic arthritis.
AB  - OBJECTIVE: To analyze the association of several autoimmune disease
      susceptibility loci in a population of patients with psoriasis and defined joint
      disease from northern Sweden. METHOD: One hundred twenty patients with psoriasis
      and defined joint disease were examined clinically, radiologically, and with
      laboratory-based analyses. Disease classification was based on peripheral and/or
      axial engagement. The tumor necrosis factor (TNF) locus, 1q21 (PSORS4), 3q21
      (PSORS5), 8q24, 16q21, and the CTLA4 gene were analyzed using a total of 38
      microsatellite markers and 2 single nucleotide polymorphisms (SNP). Ninety-four
      controls with the same ethnic background as the patients were randomly selected
      from the same region of Sweden. RESULTS: An association was found with one of the
      markers in the TNFB locus within the HLA region (p = 0.012, pc = 0.024). Three
      markers at the PSORS4 locus on chromosome 1q21 and 2 markers at the 8q24 locus
      showed nominal p values of < 0.05. After applying the Bonferroni correction for
      multiple analyses these markers did not reach significance. No other marker
      showed significant association. In a subgroup of the patients, possible linkage
      disequilibrium between the TNFB123 and HLA-B antigens, B17, B27, B37, B44, and
      B62 was analyzed. A significant linkage (p = 0.0001) was found. CONCLUSION: We
      identified an association between psoriatic arthritis and one of the
      microsatellite markers within the TNFB locus at the HLA region on chromosome 6.
      Linkage disequilibrium between TNFB123 and certain HLA-B antigens was found.

PMID- 15517638
TI  - Evaluation of bone mineral density, hormones, biochemical markers of bone
      metabolism, and osteoprotegerin serum levels in patients with ankylosing
      spondylitis.
AB  - OBJECTIVE: To evaluate bone metabolism in patients with ankylosing spondylitis
      (AS) and test the hypothesis that osteoprotegerin (OPG) serum concentrations are
      correlated with the severity of bone loss as assessed by bone mineral density
      (BMD) and biochemical markers of bone turnover. Osteoporosis occurs frequently in
      patients with AS and OPG represents a soluble decoy receptor that neutralizes
      receptor activator of nuclear factor-kB ligand (RANKL), an essential cytokine for
      osteoclast function. METHODS: Clinical data, radiographs of the spine, BMD of
      lumbar spine and the femur, biochemical markers of bone turnover, and serum
      levels of OPG were evaluated in 264 patients with AS (72% men) and 240 age
      matched healthy controls (76% men). RESULTS: OPG serum levels were significantly
      lower in patients with AS compared to controls (1.84 +/- 1.15 vs 3.54 +/- 2.18
      pmol/l, p < 0.001), and in contrast to controls, were not positively correlated
      with age. In addition, BMD of the hip and the femoral neck were significantly
      lower in patients with AS than in controls. There were positive correlations in
      patients with AS between BMD of the femoral neck and free testosterone serum
      levels in men and free estradiol serum levels in women, respectively. Patients
      with AS and osteoporosis had higher biochemical markers of bone resorption and
      inflammatory activity. CONCLUSION: Bone loss in patients with AS is associated
      with low sex steroid hormone serum levels, high biochemical markers of bone
      resorption and inflammatory activity, low OPG serum levels, and lack of
      compensatory age-related increase of OPG serum levels.

PMID- 15517639
TI  - Ultrasonographic study of Achilles tendon and plantar fascia in
      chondrocalcinosis.
AB  - OBJECTIVE: To investigate by high frequency grey-scale ultrasonography (US) and
      power Doppler sonography (PDS) the modality and frequency of involvement of the
      Achilles tendon and plantar fascia in chondrocalcinosis (CC), and to correlate
      these findings with clinical complaints and radiographic evidence. METHODS: The
      heels of 57 consecutive patients with CC were evaluated by US, PDS, and
      radiography. One control group of 50 consecutive patients with osteoarthritis
      (OA) without signs of CC was studied in the same way. A second control group of
      50 healthy subjects underwent only US/PDS examination. All subjects also
      underwent clinical assessment. RESULTS: US revealed Achilles tendon
      calcifications in 57.9% of those with CC, but none in the control groups. Plantar
      fascia calcifications were observed in 15.8% of CC and in 2% of OA cases, but not
      in healthy controls. US showed no significant difference in postero-inferior and
      inferior calcaneal enthesophytosis between subjects with CC (59.6% and 61.4%,
      respectively) and those with OA (46% and 44%, respectively). Such alterations
      were also present, in lower percentages, in the healthy controls. Posterior and
      inferior calcaneal erosions were absent in all groups. Achilles enthesopathy was
      found in 22.8% of patients with CC (14.9% of heels, with vascular signals in
      11.4% of heels on PDS). Deep retrocalcaneal bursitis was found in 10.5% of
      patients with CC (7% of heels, with vascular signals in 5.2% of heels on PDS).
      Plantar fasciitis was found in 40.3% of patients with CC (36% of heels, with
      vascular signals in 2.6% of heels on PDS) and in 14% of OA patients, but not in
      healthy controls. No significant correlation was found between talalgia or sex of
      patients and presence of calcifications. A significant correlation was observed
      between talalgia and Achilles enthesopathy (r = 0.78, p < 0.0001), deep
      retrocalcaneal bursitis (r = 0.7, p < 0.0001), and plantar fasciitis (r = 0.31, p
      < 0.001). A significant correlation between talalgia and vascular signals on PDS
      was observed in Achilles enthesopathy (r = 0.91, p < 0.0001) and deep
      retrocalcaneal bursitis (r = 0.65, p < 0.0001). The presence of vascular signals
      on PDS was significantly associated with the presence of tendinous and bursal
      grey-scale US alterations. Achilles tendon calcifications were 39% sensitive,
      100% specific, and 77% accurate for the presence of CC, whereas plantar fascia
      calcifications were 15% sensitive, 98% specific, and 54% accurate. Excellent
      agreement was found between US and radiography in detecting Achilles tendon
      calcifications (k = 0.86), plantar fascia calcifications (k = 0.77), postero
      inferior enthesophytosis (k = 0.90), and inferior enthesophytosis (k = 0.83).
      CONCLUSION: Calcaneal tendon calcifications are frequent and asymptomatic
      findings in patients with CC, and they have a high specificity for this disease.
      US shows high agreement with radiography in depicting calcifications and
      enthesophytosis. Inflammatory changes of the calcaneal soft tissues are
      frequently observed by US and PDS in patients with chondrocalcinosis.

PMID- 15517640
TI  - Efficacy of continuous passive motion following total knee arthroplasty: a
      metaanalysis.
AB  - OBJECTIVE: The objective of this metaanalysis is to examine the effectiveness of
      continuous passive motion (CPM) following total knee arthroplasty (TKA). METHODS:
      This metaanalysis used the methodology proposed by the Cochrane Collaboration.
      RESULTS: This review of 14 studies (952 patients) found significant improvements
      in active knee flexion and analgesic use 2 weeks postoperatively with the use of
      CPM and physiotherapy (PT) compared to PT alone. In addition, length of hospital
      stay and need for knee manipulations were significantly decreased in the CPM
      group. Not enough data were available to compare the degree of knee flexion
      applied or number of hours of application of CPM. However, significant results
      were not found for other comparisons such as short term CPM application versus
      longterm CPM application and wide treatment range versus small treatment range
      for the outcomes of active knee flexion, passive knee flexion and extension,
      presence of a fixed flexion deformity, use of analgesic, or total knee range of
      motion. CONCLUSION: CPM combined with PT may offer beneficial results for
      patients post-TKA. However, the potential benefits will need to be carefully
      weighed against the inconvenience and expense of CPM. More research is necessary
      to assess the differences in effectiveness with different characteristics of
      application such as total duration of treatment and intensity of CPM
      interventions.

PMID- 15517641
TI  - Intraarticular corticosteroid injection: pain relief in osteoarthritis of the
      hip?
AB  - OBJECTIVE: Osteoarthritis (OA) is one of the most common causes of morbidity in
      the elderly population, and surgery is often preceded by years of pain and
      disability. Intraarticular corticosteroid injections in osteoarthritic joints may
      play a role in the therapeutic plan and can afford quick pain relief but do not
      alter the underlying disease. There is a paucity of well controlled studies that
      provide recommendations for the use of corticosteroids in OA of the hip. METHODS:
      A prospective analysis of 80 patients with OA of the hip and pain at rest and on
      bearing weight for more than 4 weeks was performed. Patients were randomized into
      2 groups; group 1 (n = 40) received corticosteroid (80 mg triamcinolone
      acetonide) and group 2 (n = 40) local anesthetic (1% mepivacaine), injected into
      the hip joint under fluoroscopy. Pain, functional ability, range of motion of the
      joint, and analgesics consumed were registered 3 weeks postinjection. The
      treatment was blind for the patients and the investigators performing the
      followup. RESULTS: Pain for all modalities decreased after corticosteroid
      injection, but pain at rest decreased the most. There was significant pain
      reduction at the 3 (and 12) week followup. Joint range of motion increased
      significantly for all directions. Functional ability improved significantly after
      injection. We found no significant pain relief or improvement of functional
      ability in patients treated with local anesthetics. CONCLUSION: This study
      suggests that intraarticular corticosteroids might improve pain and range of
      motion of the affected joint in patients with hip OA.

PMID- 15517642
TI  - Can early diagnosis and management of costochondritis reduce acute chest pain
      admissions?
AB  - OBJECTIVE: We identified patients presenting with chest pain diagnosed as
      costochondritis by a consultant rheumatologist. The time taken to diagnosis was
      determined and the influence of diagnosis on subsequent management was assessed.
      We then estimated any cost benefits that early diagnosis and treatment of
      costochondritis might confer. Finally, we evaluated our current experience of
      sulfasalazine as a treatment for recurrent costochondritis. METHODS: This was a
      retrospective observational study of 25 consecutive patients (17 female), mean
      age 50 years (range 26-75), with costochondritis who initially presented with
      acute chest pain. RESULTS: The mean time to diagnosis was 9.4 (0-57) months. The
      total number of chest pain admissions pre-review was 39 compared with 6 post
      review (p < 0.0001). The number of minor investigations was 169 pre-review
      compared with 17 post-review (p < 0.0001), and major investigations 30 compared
      with 0 (p < 0.01). All 13 patients treated with corticosteroid injections
      reported symptomatic improvement, and 10 of the 11 whose symptoms recurred
      responded to sulfasalazine. CONCLUSION: Patients with costochondritis frequently
      present with acute chest pain, often resulting in multiple admissions and
      investigations. In this study admission and investigation rates were
      significantly reduced following rheumatological review. How much of this
      reduction is directly a result of rheumatological intervention is unclear, given
      the limitations of the study. The findings suggest early review may improve
      patient care and reduce expenditure; in recurrent cases of costochondritis,
      sulfasalazine may be of additional longterm benefit.

PMID- 15517643
TI  - Physiological risk factors for falls in older people with lower limb arthritis.
AB  - OBJECTIVE: To investigate physiological risk factors for falls in people with
      self-reported lower limb arthritis. METHODS: Six hundred eighty-four community
      dwelling men and women aged 75-98 years (mean 80.0, SD 4.4), categorized with and
      without lower limb arthritis, underwent quantitative tests of strength,
      peripheral sensation, vision, reaction time, balance, and pain. A 12-month
      history of falls was also obtained. RESULTS: Subjects with self-reported lower
      extremity arthritis performed significantly worse in tests of knee and ankle
      muscular strength, lower limb proprioception, postural sway, and leaning balance
      than subjects without lower extremity arthritis, while being comparable in
      vision, tactile sensitivity, and reaction time. This pattern of specific
      impairments was also evident when group results for the arthritis subjects were
      compared with community normative values and presented as a physiological
      profile. The arthritis group suffered significantly more falls [relative risk
      (RR) 1.22, 95% CI 1.03-1.46] and injurious falls (RR 1.27, 95% CI 1.01-1.60) in
      the previous 12 months than the nonarthritis group. Within the arthritis group,
      reduced knee extension strength and increased sway were identified as significant
      predictors of falls. CONCLUSION: Older people with lower limb arthritis are at
      increased risk of falling due to deficits in neuromuscular systems. A
      physiological falls-risk profile based on mean test scores for the arthritis
      group highlights deficits in muscular strength, knee proprioception, and standing
      balance, indicating the need for targeted falls prevention interventions for this
      population.

PMID- 15517645
TI  - HLA and susceptibility to juvenile idiopathic arthritis: a study of affected
      sibpairs in an isolated Finnish population.
AB  - OBJECTIVE: To determine the effects of class I (A, B, and C) and II (DRB1 and
      DQB1) HLA loci alleles and DRB1-DQB1 haplotypes on genetic susceptibility to
      juvenile idiopathic arthritis (JIA) in families with 2 or more affected siblings.
      METHODS: A total of 83 affected siblings belonging to 38 families and
      corresponding to 50 affected sibpairs, their parents, and 45 healthy sibs were
      typed for HLA in A, C, B, DRB1, and DQB1 loci. Two study designs were used to
      explore linkage and association: a case-population control design and a family
      design using the linkage method: identical-by-descent (IBD) allele-sharing and
      the association analysis methods. Associations in family data were analyzed using
      the independent transmission disequilibrium test (TDT) for linkage in the
      presence of association. This was supplemented by the family-based association
      test (FBAT) to look for association in the presence of linkage, and is robust for
      population stratification and phenotype-based selection of data. RESULTS:
      Significantly increased HLA allele frequencies among the affected siblings
      compared to Finnish bone marrow donors were observed for HLA alleles Cw4 (odds
      ratio, OR, 1.7), B27 (1.8), B35 (1.7), and DR8 (3.7). The observed ratio of
      sharing 0, 1, and 2 HLA haplotypes (A, C, B, DRB1, and DQB1) among affected
      sibpairs (ASP) was 10:23:17, significantly different from expected (p < 0.001),
      using a formula that takes into account disease prevalence and the sibling
      recurrence risk. In the univariate association analysis, both independent TDT and
      FBAT found significantly increased transmission of the DRB1*0801 and DQB1*0402
      alleles and Cw*0401. Independent positive allele effects of Cw*0401, DRB1*0801,
      and DQB1*0402 as well as negative effects of Cw*0701 and DQB1*0302 were shown by
      the family-based association analysis of the joint allele main effects. Multi
      allelic test for association of each locus confirmed significant associations of
      the DRB1 and DQB1 loci in the risk of JIA. We found DRB1*0801/DQB1*0402 haplotype
      to be strongly associated (p < 0.001) with JIA, supporting findings of the
      haplotype associations-based ASP design. CONCLUSION: Both linkage analysis of the
      affected sibpairs and association analysis of nuclear families with JIA provided
      overwhelming evidence of the major contribution of HLA to genetic susceptibility
      to JIA. The association analysis of HLA-A, C, B, DRB1, and DQB1 alleles by both
      TDT and FBAT tests confirmed in the Finnish population that the most significant
      associations prevailed for DRB1*0801, DQB1*0402, as expected from previous
      observations, and supported the independent role of Cw*0401.

PMID- 15517646
TI  - Etanercept does not essentially increase the total costs of the treatment of
      refractory juvenile idiopathic arthritis.
AB  - OBJECTIVE: To assess the costs of adding etanercept to the prevailing drug
      therapy for a one-year period in a group of 31 children with juvenile idiopathic
      arthritis (JIA) whose disease was refractory to conventional disease modifying
      antirheumatic drugs. METHODS: The changes in total costs were retrospectively
      collected from medical records and by interviewing parents 6 months before the
      initiation of etanercept treatment and during a 12-month followup divided into 3
      month periods. RESULTS: Direct median costs increased during the first 3 months
      after the introduction of etanercept, but decreased later during the followup.
      The estimated median direct costs per patient increased by 4200 US dollars per
      year, and the indirect costs were reduced by 50%, i.e., 1700 US dollars . The
      estimated median total cost per patient was increased by about 2700 US dollars
      per year (10%). CONCLUSION: After combining etanercept with the prevailing
      treatment, the total costs of refractory JIA calculated per year were only
      slightly higher than those of traditional therapy. This finding must be evaluated
      in light of the reduced inflammatory activity of the joint disease and the
      probable reduction of lifetime pain and disability produced by the disease.

PMID- 15517647
TI  - Preliminary criteria for clinical remission for select categories of juvenile
      idiopathic arthritis.
AB  - OBJECTIVE: To develop preliminary criteria for inactive disease and clinical
      remission for select categories of juvenile idiopathic arthritis (JIA), and to
      decide what such clinical states should predict in terms of probability of
      disease recurrence. METHODS: A Delphi serial questionnaire consensus-formation
      approach was used initially to gather criteria in use by pediatric
      rheumatologists (PR) for defining clinical remission in oligoarticular
      (persistent and extended), rheumatoid factor (RF) positive and negative
      polyarticular, and systemic JIA. Results from sequential questionnaires provided
      an agenda for a nominal group technique (NGT) conference to reach consensus on
      unresolved questions. RESULTS: One hundred and thirty PR from 34 countries
      responded to the questionnaires and 20 PR from 9 countries attended the
      conference. Draft criteria for inactive disease include the following: no active
      arthritis; no fever, rash, serositis, splenomegaly, or generalized
      lymphadenopathy attributable to JIA; no active uveitis; normal erythrocyte
      sedimentation rate or C-reactive protein; and a physician's global assessment of
      disease activity rated at the best score possible for the instrument used.
      According to consensus vote, 6 continuous months of inactive disease on
      medication defines clinical remission on medication, while 12 months of inactive
      disease off all anti-arthritis (and anti-uveitis) medications defines clinical
      remission off medication. The finalized criteria for remission off medication
      ideally should predict that a patient has </= 20% probability of disease
      recurrence within the next 5 years. CONCLUSION: Using consensus formation
      techniques, we formulated preliminary criteria for inactive disease and clinical
      remission on and off medication for use in select categories of JIA.
      Retrospective validation is in progress; prospective validation will follow.
      Future efforts will include other categories of JIA.

PMID- 15517648
TI  - Incidence of vasculitis in children in the Czech Republic: 2-year prospective
      epidemiology survey.
AB  - OBJECTIVE: To determine the incidence and presenting features of primary and
      secondary vasculitides in children across the Czech Republic. METHODS: The
      population of 2.02 million children under 17 years of age was surveyed over 2
      years. Cases were identified through monthly questionnaires posted to consultant
      pediatricians in all hospital pediatric departments in the country. Patients were
      included in the analysis if they met established inclusion criteria for each
      diagnosis and had disease onset between 1997 and 1999. Incidence rates were
      calculated from population rates derived from the 1991 Census. RESULTS: We
      identified 452 new cases of vasculitis and connective tissue disease. The
      estimated annual incidence of Henoch-Schonlein purpura (HSP) was 10.2/100,000
      children, with a mean age at onset of 7 years. At disease onset palpable purpura
      was present in all cases; arthritis/arthralgia in 52%; abdominal pain and/or
      gastrointestinal bleeding in 40%; hematuria/proteinuria in 15%; and genital
      involvement in 2.8%. Forty-nine percent of all patients with HSP received short
      term corticosteroids. The estimated annual incidence of Kawasaki disease (KD) was
      1.6/100,000 children under 5 years. Thirteen percent of patients with KD had
      transient dilatation of coronary arteries; 75% received high dose intravenous
      immunoglobulin. Other primary systemic vasculitides were extremely rare in this
      population. Secondary vasculitides of connective tissue diseases had an estimated
      annual incidence of 0.22/100,000 for systemic lupus erythematosus and
      0.19/100,000 for dermatomyositis. CONCLUSION: We determined the incidence of
      different childhood vasculitides within a hospital based population throughout
      the Czech Republic. HSP was the most common, with a relatively high proportion of
      the patients treated with a short course of corticosteroids. A lower incidence
      than expected of KD raised the suspicion that some cases were not identified.
      Other childhood vasculitides were rare.

PMID- 15517649
TI  - Common aspects of human and primate seronegative arthritis.
AB  - A 27-year-old female lowland gorilla developed an asymmetric oligoarthritis 3
      months post-partum. There was no evidence of an antecedent gastrointestinal or
      genitourinary infection. Serum was negative for rheumatoid factor and antinuclear
      antibody. Synovial fluid revealed 2000 white blood cells with negative cultures
      and polarized microscopy. Studies on synoviocytes were the following: (1) FACS
      analysis revealed surface expression of a B27-like epitope of the cells. (2)
      Analysis of intracellular clearance kinetics of arthritogenic organisms showed
      peak intracellular colony-forming units at 48 hours after bacterial invasion, and
      clearance by 13 days post-invasion. (3) Interferon-y (0.1-10.0 ng/ml)accelerated
      intracellular microbicidal pathways in a dose-dependent fashion. These findings
      closely parallel those seen in human synoviocytes of patients with
      spondyloarthropathy. Primate and human seronegative arthritis share clinical and
      immunologic features, as well as aspects of host:pathogen defense mechanisms. The
      interplay of genetic and microbial factors underlying this arthritis appears to
      be conserved across these species boundaries.

PMID- 15517650
TI  - Staphylococcal endocarditis and multiple emboli in a patient with systemic lupus
      erythematosus.
AB  - We describe a patient with systemic lupus erythematosus who developed
      Staphylococcus aureus endocarditis following dental work. Multiple brain and
      cutaneous septic emboli developed despite aggressive antibiotic therapy.

PMID- 15517651
TI  - Pregnancy outcome in patients with adult onset Still's disease.
AB  - Pregnancy outcome of patients with adult onset Still's disease (AOSD) has not
      been addressed. We report the maternal and fetal morbidity of 5 pregnancies from
      3 Chinese patients with AOSD and review another 17 pregnancies from 14 patients
      reported in the English literature. Nine patients had their first manifestation
      in the 5th to 6th gestational month. Disease relapse in patients with known
      AOSDoccurred most commonly in the post-partum period. Most did not respond
      satisfactorily to nonsteroidal antiinflammatory agents alone, but responded to
      administration of corticosteroids, especially in high doses.

PMID- 15517652
TI  - Low sensitivity of anti-alpha-fodrin antibodies in patients with primary
      Sjogren's syndrome.

PMID- 15517654
TI  - MRI and 31PMR spectroscopy investigations of muscle function disclose no
      abnormality in macrophagic myofasciitis.

PMID- 15517655
TI  - Endocrine-related resources from the National Institutes of Health.

PMID- 15517656
TI  - Patient information page: hormones, women and breast cancer.

PMID- 15517657
TI  - Retraction. Prevention of renovascular and cardiac pathophysiological changes in
      hypertension by angiotensin II type 1 receptor antisense gene therapy.

PMID- 15517659
TI  - 2004 APA Achievement Award. Silver Award: Thresholds' Grais Apartments, Chicago,
      Illinois--residential treatment for adults with severe mental illness and co
      occurring substance use disorders.

PMID- 15517660
TI  - 2004 APA Achievement Award. Silver Award: TennCare Centers of Excellence for
      Children in State Custody--a successful partnership for serving a population with
      complex needs.

PMID- 15517661
TI  - 2004 APA Achievement Award. Bronze Award: Senior Outreach Program of the New York
      Service Program for Older People, Inc (SPOP)--an innovative approach to
      alleviating stigma in the mental health treatment of older adults.

PMID- 15517662
TI  - 2004 APA Achievement Award. Bronze Award: Youth and Family Centers, Dallas
      Independent School District--providing comprehensive mental health care to school
      age children and their families.

PMID- 15517663
TI  - Vocational training north of the border.

PMID- 15517664
TI  - Anatomy of the obturator region: relations to a trans-obturator sling.
AB  - Our objective was to determine the relationships between a trans-obturator sling
      and anatomic structures within the obturator region. The obturator regions of six
      cadavers were dissected and distances from the mid-point of the ischiopubic ramus
      to the muscles, nerves, and vessels of the region were measured. A trans
      obturator sling was placed and distances from the device to the same anatomic
      structures were determined. Four additional cadavers were dissected to determine
      the device route of passage. The obturator canal is on average 4.4 cm from the
      midpoint of the ischiopubic rami. The trans-obturator sling passes on average 2.4
      cm inferior-medial to the obturator canal. The anterior and posterior divisions
      of the obturator nerve are on average 3.4 and 2.8 cm, respectively, from a passed
      trans-obturator device. The device passed on average 1.1 cm from the most medial
      branch of the obturator vessels. Vascular and nerve structures are within 1-3 cm
      of the path of any device passed through the obturator foramen. A trans-obturator
      sling risks injury to these structures, although the small caliber of the vessels
      and the confined space in which they would bleed make the consequences of injury
      uncertain.

PMID- 15517665
TI  - Suburethral tape via the obturator route: is the TOT a simplification of the TVT?
AB  - Suburethral meshes can be implanted via the classic retropubic route (TVT) or by
      a new insertion technique that passes the tape into the obturator foramen (TOT).
      In a retrospective study we compared one 18-month period of 94 TOT (tension-free
      obturator tape) and one 18-month period of 99 TVT (tension-free vaginal tape),
      which preceded the change in the approach route. All operations were performed by
      the same surgeon using the same Prolene mesh and with no other surgical procedure
      associated. These two series were similar in terms of patient age, previous
      surgical history, degree of incontinence and preoperative urethral closure
      pressure. The analysis shows more hemorrhagic complications in the TVT group
      (10%) than in the TOT group (2%), but the difference was not significant. Bladder
      injuries were more frequent in the TVT group (10%) than in the TOT group (0%),
      but there was one urethral injury in the TOT group. The mean follow-up was 29.5
      months in the TVT group and 12.8 months in the TOT group. The urinary results
      were the same, with 90% and 95% cured, respectively. In conclusion, the obturator
      approach shows identical urinary results to the classic retropubic approach.
      Because of the nature of the procedure, major hemorrhage and bowel perforation
      are excluded in the TOT procedure. Thus simplicity, safety and continence result
      mean that the obturator approach represents the best method of suburethral tape
      insertion for the treatment of urinary stress incontinence.

PMID- 15517666
TI  - Bladder weight in perimenopausal women aged 50-55.
AB  - This study aimed to determine whether the preliminary factor for the
      manifestation of lower urinary tract symptoms (LUTS) in perimenopausal women is
      age-dependent morphological changes in the bladder or hypoestrogenism. The
      bladder weights and the effects of bladder weight changes on LUTS were evaluated
      in three groups of women within and age range of 50-55 years: premenopausal (n =
      29), short-term menopausal (less than 5 years) (n = 38) and long-term menopausal
      (5 years and more) (n = 31). The comparison of LUTS among the groups was made
      using the International Prostate Symptom Score (IPSS) questionnaire; the
      ultrasonographically determined bladder weights of all the women and the duration
      of menopause were evaluated for the presence of any correlation for their ages.
      The relation between the bladder weights and the symptom scores was also tested.
      The bladder weight of women with longer duration of menopause was found to be
      significantly decreased compared with that of women with shorter-duration
      menopause within the same age group (p < 0.05). There was significant correlation
      between the increased duration of menopause and the decrease in the bladder
      weight (r = 0.2, p = 0.015). When all the women were taken into account, there
      was no correlation between the ages and bladder weights (r = 0.03; p = 0.76).
      There was no significant difference among the groups in terms of symptom scores
      evaluated as single scores, total symptom scores, total irritative and
      obstructive scores (p > 0.05 for each). The symptom scores had no correlation
      with the bladder weights or the ages of patients (p > 0.05 for each). In this age
      group of women the duration of hypoestrogenism does not seem to cause a
      difference in the symptom scores. To observe a possible significant difference,
      it is necessary to evaluate older women or women with a longer duration of
      hypoestrogenism. These findings suggest the cause for the decreased bladder
      weight to be the higher duration of hypoestrogenism rather than the older age.

PMID- 15517667
TI  - Medium-term follow-up on use of freeze-dried, irradiated donor fascia for
      sacrocolpopexy and sling procedures.
AB  - The aim of this study was to document longer-term follow-up of patients in a
      previously reported series who underwent either sacrocolpopexy (SCP) or
      suburethral sling procedures utilizing freeze-dried, irradiated donor fascia.
      Subjects from the initial series of 67 SCPs and 35 slings were included in this
      retrospective chart review of postoperative follow-up where surgical follow-up
      longer than 3 months from the procedure was available. Subjects undergoing SCP
      were examined at the time of any clinical visit and their pelvic organ support
      evaluated utilizing the POP-Q system. The SCP procedure was considered to be
      unsuccessful if any anterior vaginal wall point (Aa or Ba) was at the hymen or
      beyond, or if the vaginal apical point (C or D) descended to a point at least
      halfway to the hymen from a position of perfect apical support. Subjects who did
      not return for clinical examination after their 3-month postoperative visit but
      who had been in telephone contact with the clinic stating that they had
      experienced symptomatic recurrence of their POP were also included as having
      unsuccessful SCP procedures. Those similarly in contact with the office by
      telephone, but not clinically examined, who indicated no subjective return of
      their POP, were coded as successful. The outcome of the sling procedure was
      primarily evaluated subjectively, with the patient indicating that stress
      incontinence symptoms were present or absent. Follow-up was available for 75
      patients, who had undergone 54 SCP and 27 sling procedures (6 patients had
      undergone both SCP and sling procedures). When failure was defined according to
      any of the criteria listed in the methods section, 45 (83%) patients experienced
      SCP failure at a median of 12 months after surgery. A total of 14 (52%) sling
      procedures were failures, with recurrent SUI symptoms experienced from 2 weeks to
      24 months (median 3 months) after the procedure. One year after surgery, 23 (43%)
      SCPs were known to be failures, and 11 (41%) slings were known to be failures.
      The remaining 13 (48%) slings were subjectively successful when last seen 7-51
      months after surgery. We reoperated on 21 (40%) patients. At the time of repeat
      SCP (chosen by 16 patients) we found graft between the sacrum and vagina in just
      3 patients (19%). The use of freeze-dried, irradiated donor fascia for both SCP
      and sling procedures was associated with an unacceptably high failure rate in our
      series.

PMID- 15517668
TI  - A comparison of extended-release oxybutynin and tolterodine for treatment of
      overactive bladder in women.
AB  - Women with urge or mixed incontinence were randomized to a daily dose of 10 mg
      extended-release oxybutynin chloride (qd) or tolterodine tartrate 4 mg (2 mg bid)
      for 12 weeks. Subjects completed 7-day voiding diaries at baseline and at 12
      weeks. A total of 315 women were treated. At the end of the study, extended
      release oxybutynin chloride was more effective than twice-daily tolterodine
      tartrate as measured by urge and total incontinence episodes (p=0.038, p=0.030,
      respectively). Overall, the reduction in micturition frequency between groups was
      not significantly different. In women aged 64 years and younger (comprising 63%
      of the population) extended-release oxybutynin was more effective than
      tolterodine for urge (p=0.005) and total incontinence (p=0.005), and for
      micturition frequency (0.024). Adverse events were infrequent, mostly mild, and
      similar between treatment groups. We concluded that daily extended-release
      oxybutynin chloride (10 mg) was more effective than tolterodine tartrate (2 mg
      bid) in treating urge and total incontinence. The incidences of dry mouth, CNS
      events, and other adverse events were similar for both drugs.

PMID- 15517669
TI  - Voiding function after a modified no-tension pubovaginal sling.
AB  - Voiding dysfunction following sling procedures for correction of genuine stress
      urinary incontinence (GSI) is a frequently reported complication. This study
      sought to determine if voiding dysfunction could be reduced by eliminating sling
      tension against the urethra. Participants were diagnosed with GSI and randomized
      to one of two surgical groups. One received a conventional suburethral sling and
      the other received a modified sling placed at the mid-urethra without tension.
      Voiding trials after surgery monitored for voiding dysfunction. Multichannel
      urodynamic studies were performed pre- and post-operatively. Cure rates for GSI
      were similar for the two groups (91.7 vs. 88.5%). The 27 patients in the modified
      group voided an average of 5 days earlier than the 21 patients in the
      conventional group. Conventional group patients were more likely to have urinary
      retention (125 vs. 49 cc, p=0.03). The modified group had a lesser change in
      average closure pressure following surgery. Results suggested a higher increase
      in urethral resistance in the conventional group (0.72 vs. 1.88 cm H2O ml(-2)
      sec2). No differences were seen in symptomatic urinary urgency or urge
      incontinence following surgery. This study demonstrated a no-tension sling at the
      mid-urethra to afford equivalent cure of GSI with significant reduction of
      voiding dysfunction.

PMID- 15517670
TI  - Abdominal hysterectomy and Burch colposuspension for uterovaginal prolapse.
AB  - The recurrence rate for prolapse in patients who underwent abdominal hysterectomy
      and sacrocolposuspension for genital prolapse were determined. Patient records
      were reviewed and 58 patients who had undergone abdominal hysterectomy for
      genital prolapse and sacrocolposuspension with mesh were included. The patients'
      median age was 47.0 years and parity 3. Preoperatively, 25 patients (43%)
      presented with bladder symptoms, 17 (29%) with bowel symptoms and 45 (78%) with
      something protruding through the vagina. All patients underwent hysterectomy, of
      which 51 (88%) were subtotal. Colposuspension was performed by inserting a mesh
      from the mid-vagina to the sacrum (S1). A Burch colposuspension was performed in
      50 patients (87%). The median follow-up was 20 months. Six patients (10%)
      developed recurrent prolapse, of which five (9%) underwent repeat surgery. There
      were no mesh erosions. The recurrence rate for prolapse was low, indicating that
      abdominal hysterectomy with sacrocolposuspension is an excellent option for
      uterovaginal prolapse.

PMID- 15517671
TI  - Bulking agents for stress urinary incontinence: short-term results and
      complications in a randomized comparison of periurethral and transurethral
      injections.
AB  - The purpose of our study was to compare the two standard routes of urethral
      bulking injection in a prospective randomized trial. Forty women with genuine
      stress incontinence (n = 36), or mixed incontinence with a minor and controlled
      urge component (n = 4), participated in a urethral bulking agent trial. All
      patients had a standardized preoperative evaluation which included history,
      physical examination, assignment of incontinence status on a Stamey grading
      scale, postvoid residual (PVR) determination, Valsalva leak-point pressure,
      maximal urethral closure pressure, functional urethral length, Q-tip excursion
      angle, quantitative pad test, and completion of a quality of life questionnaire.
      On the day of injection they were randomly assigned to a periurethral or
      transurethral route of injection based on a computer-generated block
      randomization scheme. An ultrasound-determined PVR was obtained on all patients
      after injection. If self-catheterization was necessary, and the PVR was > 200 ml,
      urinary retention was diagnosed. Postoperative assessment included a patient
      interview, subjective assessment of improvement, PVR, voiding diary, and
      assignment of incontinence grade. At the screening visit there were no
      significant differences between the groups for any variables except type of
      stress incontinence. With short-term follow-up both transurethral and
      periurethral routes of injection seem to be equally efficacious. In the
      periurethral injection group there was a higher rate of postoperative retention;
      this group had a significantly higher volume of injectable agent used. There was
      no significant difference in risk of urinary tract infections between the two
      groups. We conclude that both periurethral and transurethral methods of bulking
      agent injection for stress urinary incontinence are equally efficacious, with
      minimal morbidity.

PMID- 15517672
TI  - Sulfated glycosaminoglycans of the vagina and perineal skin in pre- and
      postmenopausal women, according to genital prolapse stage.
AB  - The aim of this study was to analyze the amount and types of sulfated
      glycosaminoglycans (GAGs) of the extracellular matrix (ECM) in the posterior
      vaginal wall and perineal skin in menacme and postmenopausal women, according to
      genital prolapse stage. Samples of vaginal tissue and perineal skin were obtained
      from 40 women who underwent vaginal surgery. Sulfated glycosaminoglycans were
      extracted by extensive tissue maxatase digestion, submitted to electrophoresis on
      agarose gel, and their concentrations were determined by densitometry. Dermatan
      sulphate (DS) was the predominant GAG, followed by chondroitin sulfate (CS) and
      heparan sulfate (HS). In the vagina there was a significant decrease in total
      GAGs, CS, DS and HS in postmenopausal women with prolapse stage 2 and 3 compared
      to the premenopausal group, independent of the stage. In stage 2 and 3
      postmenopausal patients there was a significant decrease of DS and HS compared to
      the stage 1 postmenopausal group. In perineal skin there was no significant
      difference between total GAG amount, DS and HS. However, the amount of CS in
      premenopausal stage 1 patients was significantly than that in postmenopausal
      patients stage 1 and stages 2 and 3. In conclusions, there are quantitative and
      qualitative differences in GAGs of the ECM in vaginal wall and perineal skin
      between women in menacme and the postmenopause, according to genital prolapse
      stage.

PMID- 15517673
TI  - Study on nerve fiber density in anterior vaginal epithelium for stress urinary
      incontinence.
AB  - The aim of this study was to determine the relationship of innervation in
      anterior vaginal epithelium with the etiology of stress urinary incontinence
      (SUI). Fifty-three biopsy specimens of the anterior vaginal epithelium were
      obtained from 53 subjects in control, pelvic organ prolapse (POP) and SUI groups.
      Routine HE staining and immunohistochemical staining for protein gene product 9.5
      (PGP9.5) were performed for all specimens. PGP9.5 immunoreactivity was identified
      in nerve fibers and cells of the epithelium and subepitheliual connective tissue
      of vagina. The nerve fiber profiles of vaginal epithelium in the SUI/POP groups
      were significantly lower than those in the control group (P < 0.05). There was no
      correlation between the nerve fiber profiles and parity in SUI, POP and control
      groups. Decrease of nerve fiber profiles in anterior vaginal epithelium might
      lead to the occurrence of SUI.

PMID- 15517674
TI  - Comparison of measurements obtained with microtip and external water pressure
      transducers.
AB  - The aim of this study was to compare pressure readings obtained with catheter
      mounted microtip and external water pressure transducers using a mechanical model
      for vesical pressure during Valsalva straining and coughing. The two catheter
      mounted pressure transducers were simultaneously placed in a vinyl i.v. bag
      designed to mimic the parameters of the human bladder to allow comparison of
      simultaneous readings from both transducers. Simulated cough and Valsalva
      maneuvers of various strengths at different volumes (100 ml, 200 ml, 300 ml) were
      performed and the pressure readings generated by the two systems compared. The
      Pearson correlation coefficient between the systems was 0.998 for coughs and
      0.998 for Valsalva efforts. Data were also analyzed by volume and strength of
      simulated cough and Valsalva effort, and correlations were found to be high (> or
      = 0.940) for all subgroup analyses. Mean absolute differences between events
      recorded by the two systems were small, as indicated by the y-intercept of 3.76
      cmH2O pressure. Neither transducer recorded consistently higher pressures than
      the other. We concluded that there is a high correlation between pressure
      measurements obtained from microtip and external water pressure transducers
      during simulated cough and Valsalva efforts in this model. As similar correlation
      should exist in vivo, urodynamic data generated by the two transducer types
      should be comparable.

PMID- 15517675
TI  - Prospective 3D ultrasonographic evaluation of immediate postpartum urine
      retention volume in 100 women who delivered vaginally.
AB  - Our objective was to determine the reproducibility and validity of urine
      retention volumes measured by 3D ultrasonography (3D-US) 2 h postpartum. This was
      a longitudinal prospective study of 100 women who delivered vaginally. Each woman
      underwent five successive urine retention measurements with the Bladder Scan 2 h
      after vaginal delivery, followed by transurethral catheterization to determine
      the real volume. The reproducibility of only the last four scan values was
      analyzed with an intraclass correlation coefficient, and that of determinations 4
      and 5 with a Bland-Altman plot. The validity of the device was similarly
      evaluated using the mean four-scan and real values. Pearson's correlation
      coefficient was calculated and a least-trimmed squares robust linear-regression
      model was used. All tests were two-sided with a 5% alpha risk. Results showed
      that 3D-US measurements were highly reproducible, with an intraclass correlation
      coefficient of 0.974 (95% CI:0.964-0.981). 3D-US also accurately estimated the
      real urine volume (intraclass correlation coefficient 0.924; 95% CI:0.888-0.949),
      but tended to underestimate by about 6.8%. The between-technique Pearson
      correlation coefficient was 0.94 (P < 0.0001) and the regression analysis gave an
      R2 of 0.914. Urine retention volumes exceeded 500 ml in 55 women, and 11 in 7. We
      concluded that 3D-US was reliably able to measure postpartum urine retention
      volume.

PMID- 15517676
TI  - Uterine preservation during surgery for uterovaginal prolapse: a review.
AB  - The traditional surgical treatment for uterovaginal prolapse has been vaginal
      hysterectomy. For many reasons, women may request uterine preservation at the
      time of prolapse surgery. The purpose of this paper is to review the medical
      literature pertaining to the role of uterine preservation during reconstructive
      surgery for uterovaginal prolapse. A MEDLINE search of literature in the English
      language (1966 to current) was carried out using the keywords 'hysterectomy',
      'hysteropexy', 'uterine preservation', 'uterine suspension' and 'uterovaginal
      prolapse.' Fourteen articles primarily addressing the surgical repair of
      uterovaginal prolapse with uterine preservation were included in this review.
      Papers primarily addressing other forms of pelvic organ prolapse, incontinence or
      obliterative procedures were excluded. Existing procedures and their clinical
      outcomes were reviewed. The current literature suggests that uterine preservation
      during surgery for uterovaginal prolapse may be an option in appropriately
      selected women who desire it; prospective, randomized trials are needed to
      corroborate this.

PMID- 15517677
TI  - Policy integration as a success factor for emissions trading.
AB  - Emissions trading will not be able to become the single instrument of a national
      climate policy because of costs for monitoring of greenhouse gases and transfers
      of allowances. Thus, it is important to assess optimal ways of integrating
      emissions trading into national climate policy mixes, thus leading to a more
      efficient policy, especially by allowing the use of transboundary transactions.
      The implemented trading systems of the UK and Denmark, the agreed EU one, and the
      planned ones of Norway are used as case studies. In the UK, the introduction of
      an energy tax on industry was the catalyst that led to the development of
      emissions trading, voluntary agreements, and two subsidy programs. However, in
      Denmark trading was limited in scope and not integrated with the successful
      emission tax. The EU and Norwegian trading schemes both have a large scope and
      integrate international transfers; the former is integrated with other
      instruments to avoid free riding. Policy integration will thus enhance the
      efficiency improvements that emissions trading can introduce.

PMID- 15517678
TI  - A soft systems approach to watershed management: a road salt case study.
AB  - Watershed management requires integration of social and ecological understanding.
      Participatory approaches to planning and management incorporate stakeholder
      knowledge and understanding. An action research strategy using focus groups with
      Michigan State University operations units helped generate a soft systems model
      of watershed impacts of organizational decision-making regarding road de-icing.
      The results reveal tensions and inconsistencies between the mission and operation
      of the institution. These tensions are exacerbated by inadequate communication
      among various elements of the campus watershed management system. The action
      research approach facilitated the researchers' understanding of the complex
      institutional system and helped identify possible areas for making improvements.
      Specifically, the researchers were able to facilitate improvement in some
      linkages between scientists developing campus watershed models and the operations
      staff responsible for handling many of the inputs being modeled.

PMID- 15517679
TI  - Entangling the complexity of protected area management: the case of Wolong
      Biosphere Reserve, southwestern China.
AB  - Protected Area (PA) management is a complex issue that requires the consideration
      of many factors and relationships. A conceptual framework for the analysis of
      biodiversity change, local human communities, and PA management was put forward,
      accordingly. Under the framework, we investigated the economic status, livelihood
      activities, biodiversity use and perceptions of local communities, and the land
      use history in Wolong Biosphere Reserve, southwestern China through household
      survey and document review in order to gain a better understanding of the
      complexity of PA management. According to the land use history, the preservation
      of agro-biodiversity, and the raising of productivity, ecological rehabilitation
      and the regulation of the human pressures are indispensable in the management of
      the reserve. Livelihood activities and the perceptions of local communities were
      largely determined by the socioeconomic background, which has important
      implications in solving the conflicts or incompatibilities in the reserve. In
      Wolong Biosphere Reserve, it is beneficial to support local farmers in solving
      their socioeconomic problems such as the overabundance of labor force and the
      lack of livelihood alternatives. Without this, there will be scarcely any
      effective biodiversity conservation and successful reserve management in the long
      term.

PMID- 15517680
TI  - Responses of three heathland shrubs to single or repeated experimental trampling.
AB  - In the last few decades, trampling has become a cause of major disturbance to
      natural areas. Trampling can occur regularly either seasonally or throughout the
      year, or as a single impact depending on a recreational activity or an event.
      This study, carried out on a coastal heathland in north Brittany (France), was
      based on the hypothesis that the vegetation response can differ depending on
      whether the trampling is repeated or due to a single event. The aim was to
      compare the resistance and the short-term recovery capacity of selected species
      in coastal heathland communities subjected to a trampling experiment, applied
      once or five times (with equal total number of passes from 0 to 800). The
      temporal distribution of the trampling did not affect the response of Erica
      ciliaris, whereas for Erica cinerea and Ulex gallii, trampling was slightly less
      damaging when applied once rather than five times. These differences could be
      linked to the lower resistance and the higher recovery capacity of E. ciliaris,
      compared with the two other species. This study also emphasized the influence of
      site location by comparing observations with previous studies. Plant resistance
      calculated here appeared to be lower than that calculated for a less stressful
      site. The relationship between plant traits and response to trampling was also
      investigated. The effects of the different times between disturbance application
      and observations of the short-term response of woody vegetation to experimental
      trampling is also discussed.

PMID- 15517681
TI  - Levels and influencing factors of noise pollution from small-scale industries
      (SSIs) in a developing country.
AB  - A study was carried out to determine levels and factors that influence noise
      pollution from small-scale industries (SSIs) in Dar es Salaam City Tanzania. Two
      sites for wood- and metalworks industries were investigated. Both sites exhibited
      equivalent noise levels higher than 90.0 dBA, the permissible exposure level
      limit for occupational noise. At a woodworks SSI, noise levels were found to
      correlate well with machine-use age, wood-feed speed, and wood-cut depth.
      Additionally, noise emanating from both types of SSIs was found to influence the
      level of environmental noise in the neighborhood of the SSIs. One woodworks SSI
      was found to have a circle of influence of about 140 m. The study concluded that
      SSIs present a serious source of environmental noise pollution in their
      neighborhoods. Noise pollution from SSIs is greatly influenced by the type of
      SSIs and the activities they carry out, the type and age of machines they use,
      their location relative to residential areas in their vicinity, and in-house
      noise control measures.

PMID- 15517682
TI  - Toward adaptive management: the impacts of different management strategies on
      fish stocks and fisheries in a large regulated lake.
AB  - We applied the adaptive management approach to analyze the demand and feasibility
      of adaptive management of fish stocks in a large regulated lake, Oulujarvi, in
      northern Finland. The process consisted of four phases: (1) analysis of the
      current state of the fisheries system (fishers, related markets and industry,
      fisheries researches and authorities, related organizations, etc.); (2) analysis
      of the objectives of different stakeholders; (3) the composition of alternative
      management strategies and assessment of their impacts; and (4) recommendations
      for future management. We used catch statistics from the period 1973-1995 to
      analyze fish stocks and fishing. Fish species involved were brown trout (Salmo
      trutta L.), whitefish [Coregonus lavaretus (L.) sl.], vendace (Coregonus albula
      L.); and pikeperch (Stizostedion lucioperca L.). Questionnaires and interviews
      were applied to ascertain the opinions of different groups of fishermen. Several
      models and cost-benefit analysis were used to assess the ecological, economic,
      and social impacts of three alternative management strategies. The results
      emphasize that when determining stocking levels and fishing regulations, the
      system should be considered as a whole, and impacts on major fish species and
      different groups of fishermen should be assessed. The stocking policy and fishing
      regulations should also be flexible to accommodate changing biotic and societal
      conditions. The key questions in applying the adaptive management process in
      Oulujarvi fisheries are how to determine clear objectives for fisheries
      management, find a fisheries management structure that provides workable
      interactions between different stakeholders, and arrange cost-effective
      monitoring. The lessons learned from the Oulujarvi experience and recommendations
      for fisheries management are relevant to other lakes with conflicting objectives
      of different stakeholders.

PMID- 15517683
TI  - Landscape character and fish assemblage structure and function in western Lake
      Superior streams: general relationships and identification of thresholds.
AB  - As part of a comparative watershed project investigating land-cover/land-use
      disturbance gradients for streams in the western Lake Superior Basin, we examined
      general relationships between landscape character and fish assemblage structure
      and function. We also examined the shape of those relationships to identify
      discontinuity thresholds where small changes in landscape character were
      associated with marked shifts in the fish assemblages. After completing a
      geographic analysis of second- and third-order watersheds in the western Lake
      Superior drainage, we randomly selected 48 streams along mature forest and
      watershed storage gradients in 2 hydrogeomorphic regions as our study sites.
      During the summers of 1997 and 1998, we used electrofishing to sample fish
      assemblages from each stream. Each of the landscape factors was significantly
      associated with fish assemblage structure and function based on analysis of
      covariance. Watershed storage was related to the greatest number of fish
      assemblage characteristics, but hydrogeopmorphic region and mature forest cover
      were strongly associated as well. The hydrogeomorphic region also mediated
      relationships between watershed character and fish assemblages. Discontinuity
      thresholds for our fish assemblages averaged 11% for watershed storage and 50%
      for watershed mature forest cover based on piecewise regression analysis.
      Although many of the landscape-fish relationships might have been manifest
      through effects on in-stream habitat, our results highlight the importance of
      management and land-use planning decisions at the watershed and landscape scales.

PMID- 15517684
TI  - Co-management of natural resources: a proposed framework.
AB  - Co-management acknowledges pragmatic developments and progression of
      institutional choice theories in natural resource management. This innovative
      concept embraces a pluralistic management approach based on the principle of
      subsidiarity and creates opportunities for the reconciliation of competitive
      property claims. This article reviews definitions of co-management, distinguishes
      it from other property rights regimes, and develops an organizational structure
      of the major elements involved. Synthesis of both experiences and literature
      leads to the development of a conceptual framework. Co-management is structured
      in terms of context, components, and linking mechanisms. In concert, these
      elements offer insight into the practice of co-management, address the
      shortcomings of institutional theories, and respond to critical issues raised in
      related literature. The framework contributes to natural resource management by
      acting as a means of identification and evaluation for such arrangements, as well
      as a systematic guide for future inquiries.

PMID- 15517685
TI  - Monitoring of seasonal variation in the water quality of Ubu river in Ekwusigo
      and Nnewi local government areas of Anambra State, Nigeria.
AB  - Investigation of the water quality of the Ubu river has been carried out. The
      upstream course of the river is slightly acidic (pH 5.45 +/- 0.23), and the
      acidity decreases along the lower courses of the river. Turbidity, surfactant,
      and iron content parameters of the river increased during the wet season, and
      these changes have been attributed to inputs from flood, leachates of soil
      erosion, and storm water runoff discharged into the river in increased quantities
      during the season. Concentrations of some metals were found to increase during
      the dry season because of absence of dilution of the river by storm water runoff.
      Most water quality parameters are within World Health Organization acceptable
      limits set for potable water, and they include most of the cationic and anionic
      constituents. Although there is no hydrocarbon or metal ion pollution, potability
      is reduced along the mid to downstream courses of the river by unacceptable
      levels of turbidity, surfactant concentration, and iron content, particularly
      during the wet season.

PMID- 15517686
TI  - Ecological risk assessment and problem formulation for Lake Uluabat, a Ramsar
      State in Turkey.
AB  - Unlike the United States and the European Union, developing countries do not have
      sufficiently structured legal and institutional systems to apply certain
      environmental management tools such as ecological risk assessment. However, it is
      important for countries with valuable environmental and ecological resources to
      have appropriate tools and to strengthen their environmental management
      capabilities and capacities for the sake of those resources. The case study
      described in this paper attempts to be a case study towards developing
      environmental management plans, especially in developing countries. The problem
      formulation step of Ecological Risk Assessment applied in this study contributed
      to the basic elements of an environmental management plan including the
      following: the partnership-building process, prioritization of the problems and
      issues of the ecosystem, and development of the action plan. Based on the
      information provided by participants from a series of workshops held to develop
      an environmental management plan for Uluabat Lake, ecosystem risks were ranked
      and an action plan was formed. The results obtained with the aid of fuzzy set
      theory provided a base for identification of the action steps by allowing
      scientific information to be included in the process. The degree to which Uluabat
      Lake's problem formulation fits into the existing legal framework of Turkey is
      also analyzed in this paper.

PMID- 15517687
TI  - Uncertainty assessment for management of soil contaminants with sparse data.
AB  - In order for soil resources to be sustainably managed, it is necessary to have
      reliable, valid data on the spatial distribution of their environmental impact.
      However, in practice, one often has to cope with spatial interpolation achieved
      from few data that show a skewed distribution and uncertain information about
      soil contamination. We present a case study with 76 soil samples taken from a
      site of 15 square km in order to assess the usability of information gleaned from
      sparse data. The soil was contaminated with cadmium predominantly as a result of
      airborne emissions from a metal smelter. The spatial interpolation applies
      lognormal anisotropic kriging and conditional simulation for log-transformed
      data. The uncertainty of cadmium concentration acquired through data sampling,
      sample preparation, analytical measurement, and interpolation is factor 2 within
      68.3 % confidence. Uncertainty predominantly results from the spatial
      interpolation necessitated by low sampling density and spatial heterogeneity. The
      interpolation data are shown in maps presenting likelihoods of exceeding
      threshold values as a result of a lognormal probability distribution. Although
      the results are not deterministic, this procedure yields a quantified and
      transparent estimation of the contamination, which can be used to delineate areas
      for soil improvement, remediation, or restricted area use, based on the decision
      makers' probability safety requirement.

PMID- 15517688
TI  - Results of the 2004 Belgian enquiry concerning Anesthesiology. What kind of help
      do we need ?

PMID- 15517689
TI  - Infections of the subcutis and skin of dogs caused by rapidly growing
      mycobacteria.
AB  - Nine dogs with panniculitis due to rapidly growing mycobacteria (RGM) were
      examined over 17 years. Dogs were two to 15 years; five were male, four were
      female. All were obese or in good condition. Antecedent injury, typically a dog
      bite or vehicular trauma, could be identified in some patients, while one bitch
      had hyperadrenocorticism. Infections involved different locations, although the
      cervicothoracic region, dorsum or flank were most often affected. Patients were
      systemically well, apart from one dog with pyrexia and two with pain or lameness.
      Cytology demonstrated pyogranulomatous inflammation, but in only one case was it
      possible to see acid-fast bacilli (AFB) in smears. Histology demonstrated chronic
      active pyogranulomatous panniculitis and dermatitis; AFB could be detected in
      only four specimens. Culture of aspirates or resected tissues demonstrated RGM in
      all cases, comprising six Mycobacterium smegmatis group and three Mycobacterium
      fortuitum group isolates. Resection of infected tissues, perioperative injectable
      antimicrobials and long courses of oral antimicrobials chosen according to
      susceptibility data generally effected a cure, although some cases recurred.

PMID- 15517690
TI  - Burundi: a population deprived of basic health care.

PMID- 15517691
TI  - Consultation, collaboration, communication...and conciliation.

PMID- 15517692
TI  - General practitioners for the next millennium: suggestions for medical curriculum
      reform.

PMID- 15517693
TI  - Lousy lament.

PMID- 15517694
TI  - From 'nanny state' to 'therapeutic state'.

PMID- 15517695
TI  - William Carlisle Reeves.

PMID- 15517696
TI  - Ocular torsion: rotations around the "why" axis.

PMID- 15517697
TI  - Effect of drain use in the early postoperative period after arthroscopically
      assisted anterior cruciate ligament reconstruction with bone-patellar tendon-bone
      graft.

PMID- 15517698
TI  - Nonoperative treatment of acute rupture of the Achilles tendon: results of a new
      protocol and comparison with operative treatment.

PMID- 15517699
TI  - Herbert Bower.

PMID- 15517700
TI  - Interferon alpha-2b as adjuvant treatment of recurrent respiratory papillomatosis
      in Cuba: National Programme (1994-1999 report).
AB  - Respiratory papillomatosis is a life-spoiling disease due to its high recurrence
      rate. Interferon (IFN)alpha-2b treatment, adjuvant to surgery, was assessed for
      its contribution to disease control and patient quality of life improvement. One
      hundred and sixty-nine patients (85 children and 84 adults) were included after
      surgical removal of the lesions followed by intramuscular IFN alpha-2b (Heberon
      alfa R, Heber Biotec), starting with 10(5) IU/Kg weight in children or 6 x 10(6)
      IU in adults, three times per week. The dose was reduced monthly, if no relapses
      occurred, until a monthly maintenance with 5 x 10(4) IU/Kgof weight in children
      or 3 x 10(6) IU in adults up to two years. In case of relapse, it was surgically
      removed and the patient returned to the higher dose level. The relapse frequency
      decreased significantly in 77 percent (69/90) of the recurrent patients both in
      children (34/46, 74 per cent) and adults (35/44, 79 per cent). Among patients
      included after their first papilloma, 67 per cent (44/66) had complete (no
      relapses) or partial (only one relapse) responses (children: 15/33, 45 per cent;
      adults 29/33, 88 per cent). One hundred and eighteen patients (73 per cent)
      concluded the treatment without lesions (children: 58 per cent; adults 82 per
      cent), while the rest showed a significant reduction in the number and size of
      lesions. IFN was well tolerated. Sixty-two patients (38 per cent) did not have
      adverse events. The main adverse reactions were fever (59 per cent), chills (24
      per cent), arthralgias and myalgias (14 per cent) and headache (10 per cent). One
      patient developed anti-IFN alpha neutralizing antibodies and became resistant to
      treatment with recombinant IFN alpha-2b; he responded to natural leucocyte IFN
      alpha. Treatment with IFN alpha-2b, as an adjuvant to surgery represents a
      favourable and safe therapeutic alternative for patients with recurrent
      respiratory papillomatosis.

PMID- 15517701
TI  - Prevention of lower limb soft tissue injuries in runners: a review.

PMID- 15517702
TI  - Isolation of the etiologic agent of Korean hemorrhagic fever. 1978.

PMID- 15517703
TI  - Using yeast to shed light on DNA damaging toxins and irradiation.
AB  - This unlikely tale of research and development takes us from a Pacific jellyfish
      to fluorescent green yeast in space, via the high tech world of pharmaceutical
      screening and an encounter with the YETI. It charts the history of academic
      research project that through multidisciplinary collaboration and innovation has
      led to a commercial venture with applications in a number of diverse fields.

PMID- 15517704
TI  - From war zones to RCN Wales. Interview by Felicity Waters.

PMID- 15517705
TI  - Erratum to "Sequential gene promoter interactions of C/EBPbeta, C/EBPalpha, and
      PPARgamma during adipogenesis" [Biochem. Biophys. Res. Commun. 319 (2004) 235
      239].

PMID- 15517706
TI  - [Cannabis can double the risk of schizophrenia. Increasing but still
      controversial knowledge of the psychological effects of the drug].

PMID- 15517707
TI  - [The Nobel Prize for survey of olfactory perception].

PMID- 15517708
TI  - [Acute otitis media is not treated according to recommendations. Survey of
      treatment patterns in emergency centers and community health centers].
AB  - Usual recommended treatment of acute otitis media (AOM) is antibiotics or
      expectancy. Different parts of Europe have varying therapy with Holland as an
      example of more restrictive use of antibiotics. The purpose with this study was
      to see differences in treatment length, choice of antibiotics, and differences in
      handling on daytime and emergency hours. 432 case records of children, aged up to
      ten years were retrospectively investigated. The result shows that antibiotics
      were prescribed to all except five patients. First choice of antibiotic (70 per
      cent) was penicillin V that also was more used at emergency hours than daytime at
      the health centre. Treatment time varied from five to ten days in contrast to
      national recommendations of five-day therapy. Registrars preferred five-day
      therapy and specialists seven days. We conclude that penicillin V is first choice
      of treatment in AOM, that treatment time varies from five to ten days without any
      underlying reasons and that expectancy was used only in very few cases.

PMID- 15517709
TI  - [Unexpected out-of-hospital deliveries--experiences from the Gothenburg area.
      Centralized obstetrical care requires competent ambulance staff].
AB  - One hundred and sixty-seven women gave birth before arrival at the hospital
      during a six-year period in the Goteborg area. Most of these women had given
      birth before. The actual delivery most often started at term during the night,
      proceeded normally but rapidly and the neonatal outcome was good. Sixty-two per
      cent of the women delivered at home. Complicated lacerations or major hemorrhages
      were uncommon. The distance to the delivery ward was one of the risk factors for
      prehospital delivery. This is important to take into consideration in the ongoing
      process of centralizing the delivery clinics. Basic knowledge in obstetrics is
      mandatory for the ambulance personnel, as well as regular observation visits to
      the delivery ward and practice in birth simulators.

PMID- 15517710
TI  - [D-dimer analysis in diagnosis of venous thromboembolism is reliable].
AB  - Analysis of D-dimer as an alternative to costly radiological examinations for
      excluding venous thromboembolism (VTE) remains controversial. In part this
      appears due to varying analytical performance of different D-dimer assay methods.
      We have evaluated a D-dimer method from BioPool, Sweden. Samples for D-dimer
      analysis were obtained from 86 consecutive patients admitted to the emergency
      unit at the Central Hospital in Kristianstad, Sweden, for symptoms consistent
      with venous thromboembolism. The result of the analysis was withheld for the
      duration of the study. In 21 patients a diagnosis of VTE was returned based upon
      radiological examination; 20 of these had D-dimer levels above the cut-off limit.
      The sensitivity for VTE using D-dimer was 95 per cent and the negative predictive
      value was 97 per cent. We conclude that D-dimer analysis in conjunction with a
      clinical investigation is helpful in excluding VTE in this category of patients.

PMID- 15517711
TI  - [Several alternatives for stroke prophylaxis in atrial fibrillation].
AB  - The anti-thromboembolic treatment of patients with atrial fibrillation is
      increasingly better recognized, partly because treatment is often suboptimal.
      Prophylactic anti-vitamin-K medication with warfarin is the most important
      principle in patients who have additional stroke risk indicators. At least one of
      the new drugs, which are currently compared with traditional treatment, seems to
      offer as effective stroke prophylaxis as high quality warfarin treatment, without
      the need of coagulation monitoring. Several alternative non-pharmacological
      methods are currently undergoing clinical evaluation. Long-term results of
      resection of left atrial appendage in association with cardiac surgery are
      explored in an ongoing randomized study. However, arguments have been raised
      against this principle, based on the physiological role of the atrial appendages
      in fluid regulation. Alternative methods for obliteration or occlusion of the
      left atrial appendage prompt further exploration.

PMID- 15517712
TI  - [Erythropoietin can reduce the effect of radiotherapy].

PMID- 15517713
TI  - [Recurrence of prolactinoma surveyed. Hormone therapy can safely be withdrawn for
      a long time in patients with normalized prolactin levels and invisible tumor].

PMID- 15517714
TI  - [Antidepressive agents can affect collection of urine and urination].

PMID- 15517715
TI  - [The Cleveland case as a lesson. Single cases and case series can be simple to
      take in but they are not suitable to secure the cause-effect relationship].

PMID- 15517716
TI  - [Blood group diet: fantasy and quackery].

PMID- 15517717
TI  - [Ethical discussions must always be implemented in the everyday work].

PMID- 15517718
TI  - [Confidentiality contra public welfare when driving under influence is
      suspected].

PMID- 15517719
TI  - [Nationalize forensic psychiatric care! Current organization takes resources from
      general psychiatry].

PMID- 15517720
TI  - [More external quality-scrutinized education for interns is required!].

PMID- 15517721
TI  - [Prosopagnosia--not a trivial matter for the sufferer].

PMID- 15517722
TI  - [Penicillin V should be administered three times daily].

PMID- 15517723
TI  - [Report from a medical safari].

PMID- 15517724
TI  - [Clitoris forgotten?].

PMID- 15517726
TI  - The voice of primary care.

PMID- 15517725
TI  - Hybrid roles spark calls to keep reassuring 'nurse' title.

PMID- 15517727
TI  - Discharge planning.

PMID- 15517728
TI  - Are employers tackling verbal abuse?

PMID- 15517729
TI  - Get fit in the Green Gym.

PMID- 15517730
TI  - Prevention and management of back pain in nurses.
AB  - Back pain is common in adults and may be associated with personal, psychosocial
      and biomechanical risk factors. Nursing is considered to be a high-risk
      occupation for back pain, but personal and work-based strategies can help to
      reduce the risk.

PMID- 15517731
TI  - What you need to know about...impetigo.

PMID- 15517732
TI  - Peripheral venous cannulation.

PMID- 15517733
TI  - Principles and limitations of pulse oximetry in patient monitoring.
AB  - Although there are many advantages to using pulse oximetry as a tool for
      monitoring oxygen saturation in arterial blood, there are also potential
      pitfalls. Nurses must understand its limitations or there is a risk that they may
      be falsely reassured by inaccurate readings. This article discusses the
      principles behind pulse oximetry and outlines some common misunderstandings.

PMID- 15517734
TI  - Diabetes article made me think beyond my neonatal specialty.

PMID- 15517735
TI  - Digital replantation following amputation due to trauma.
AB  - Digits amputated through trauma can often be replanted and regain function.
      Success depends on preoperative care of the digit and minimising the time the
      digit is without blood supply. Long-term patient compliance with postoperative
      care and therapy is necessary to maximise postoperative functioning.

PMID- 15517736
TI  - Risk of pressure damage for women using maternity services.
AB  - Pressure ulcer prevention and maternity services are areas of health care that
      are rarely linked. However, anecdotal evidence appears to support the view that
      increasing numbers of women develop pressure damage during childbirth (Malone,
      2000; Newton and Butcher, 2000). This is becoming an area of concern for
      clinicians and risk managers (Butcher, 1999).

PMID- 15517737
TI  - New guidelines for the treatment and management of people who self-harm.
AB  - People who self-harm often receive unsympathetic and inadequate health care in
      terms of both their physical and mental health needs. In order to address this
      shortfall, the National Institute for Clinical Excellence (2004) has published
      guidelines on the treatment and management of these patients. The aim is to
      ensure people who self-harm are treated with respect and compassion, and that
      staff who come into contact with these patients receive appropriate training to
      enable them to understand and engage with them and provide the care they require.
      People who self-harm should be involved in the development and delivery of this
      training. Local services are required to review their practices with regard to
      self-harm in the light of the NICE guidelines, and to implement their
      recommendations as quickly as possible.

PMID- 15517738
TI  - Assessing pain at wound dressing-related procedures.
AB  - This article is an abstract from a new guide, Principles of Best Practice:
      Minimising Pain at Wound Dressing-Related Procedures. It is an educational
      initiative of the World Union of Wound Healing Societies (WUWHS). The guide has
      been inspired by two seminal documents: the European Wound Management
      Association's position document, Pain at Wound Dressing Changes (EWMA, 2002), and
      Practical Treatment of Wound Pain and Trauma: A Patient-centred Approach (Reddy
      et al, 2003). As an international educational initiative, the WUWHS document is
      aimed at anyone involved in dressing-related procedures anywhere in the world.
      This article summarises the section on best practice in the assessment of wound
      pain.

PMID- 15517739
TI  - Making an impression in the workplace.

PMID- 15517740
TI  - The ugly business of undercutting colleagues.

PMID- 15517741
TI  - Complaints require action not evasion.

PMID- 15517742
TI  - Clinical usage of honey as a wound dressing: an update.

PMID- 15517743
TI  - Comparing the contractile properties of human fibroblasts in leg ulcers with
      normal fibroblasts.
AB  - OBJECTIVE: The tissue contraction phenomenon associated with wound healing is of
      prime importance for wound closure. Contractile properties of human fibroblasts
      from chronic venous leg ulcers were compared with those of normal fibroblasts
      using in vitro models. METHOD: Biopsies were taken from the uninvolved skin of
      the thigh, the epithelialised ulcer edge and the non-epithelialised ulcer centre
      in four patients (average age: 78 years). Fibroblasts were obtained by an explant
      technique and expanded in vitro in Dulbecco's Modified Eagle's Medium
      supplemented with 10% foetal calf serum and used for the assays at their fourth
      passage. Intracellular alpha-smooth muscle actin expression (alphaSM-actin) was
      studied by immunofluorescence labelling of cells cultured in monolayer.
      Contractile properties were evaluated using three-dimensional collagen lattices.
      RESULTS: Fibroblasts from the ulcer centre were the richest cells in actin
      filaments. Both populations of venous ulcer fibroblasts contracted more rapidly
      and to a greater extent than normal fibroblasts. The peak contractile forces
      developed by fibroblasts from the ulcer centre and the ulcer edge were 30% and
      18% greater than normal fibroblasts respectively. CONCLUSION: Some functions of
      fibroblasts, in particular the generation of contractile forces and the formation
      of cytoplasmic actin filaments, seem not to be affected in chronic venous ulcers.
      DECLARATION OF INTEREST: This study was supported by the Fondation Coloplast pour
      la Qualite de la Vie of France.

PMID- 15517744
TI  - Infection prophylaxis of gunshot wounds using probiotics.
AB  - OBJECTIVE: To report a new method of surgical infection prophylaxis for
      postoperative gunshot wounds to the extremities. METHOD: Gunshot wounded animals
      were divided into three groups: treatment (probiotic Sporobacterin), antibiotic
      (cephalosporin cefamezin) and control (no treatment). Histological studies of
      wound-bed tissue were taken on days 1, 3, 5 and 10 of the study. RESULTS: The
      probiotic administered per os was more effective than antibiotics for prophylaxis
      of surgical infection. CONCLUSION: The probiotic's effect is based on the natural
      defence mechanism activated after injury--the bacterial translocation of
      saprophytic bacteria from the gut to the wound. DECLARATION OF INTEREST: None.

PMID- 15517745
TI  - The release of zinc ions from and cytocompatibility of two zinc oxide dressings.
AB  - OBJECTIVE: These in vitro studies examined the release of zinc ions from and the
      response of human dermal fibroblasts to two zinc oxide-medicated dressings: one
      with zinc oxide in an ointment base and one using polyvinylpyrrolidone (PVP), a
      hydrophilic polymer for the binding of zinc oxide particles. METHOD: Zinc release
      from the dressings in buffered-saline (pH 7.4) was studied through a high-pore
      density membrane (pore size, 0.40 microm) in a two-compartment model at 37
      degrees C for three hours. Cytocompatibility of the dressings and 500 micromol/l
      of zinc ions was assessed using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide) assay after exposure to monolayers of confluent
      normal human dermal fibroblasts to the dressing extracts for four hours. RESULTS:
      The zinc release rate from PVP-bound zinc oxide was more than two-fold higher
      than from zinc oxide in the ointment. Extract of the zinc oxide ointment,
      containing 150 micromol/l solubilised zinc, elicited a cytotoxic reaction, while
      the zinc oxide-PVP extract, containing 410 micromol/l solubilised zinc, and 500
      micromol/l zinc chloride were non-cytotoxic to the fibroblasts. CONCLUSION: Zinc
      release in a simulated wound milieu appears to be inhibited when zinc oxide is
      incorporated in a lipophilic vehicle. It is hypothesised that the ointment
      vehicle induced cytotoxicity rather then the solubilised zinc oxide. DECLARATION
      OF INTEREST: None.

PMID- 15517746
TI  - An evaluation of non-adherent wound-contact layers for acute traumatic and
      surgical wounds.

PMID- 15517747
TI  - The prevention of heel pressure ulcers using a hydropolymer dressing in surgical
      patients.
AB  - OBJECTIVE: A trial of a self-adhesive hydropolymer foam dressing (Tielle, Johnson
      & Johnson) demonstrated that it prevented the development of friction-generated
      pressure ulcers on the heels of ICU patients. Following the trial, use of the
      foam dressing became a standard preventive measure in the ICU and the prevalence
      of heel ulcers decreased by 72% in two years. This follow-up study evaluated the
      foam's effectiveness in preventing heel pressure ulcers in surgical patients.
      METHOD: A total of 140 surgical patients were screened over a four-month period.
      They were assigned to one of two groups, depending on their pressure ulcer risk
      score and the anticipated length of the surgical procedure. The foam dressing was
      used as a barrier on the heels, depending on the patient's risk status, which was
      assessed using a modified Norton scale, and the duration of their surgery. Heels
      were inspected on a daily basis for up to 10 days. All 23 patients in the group
      whose surgery lasted less than 90 minutes dropped out of the study as they were
      discharged with insufficient data. RESULTS: A 76.7% reduction in heel pressure
      ulcers was achieved with this preventive measure. CONCLUSION: Use of an adhesive
      foam dressing on surgical patients can prevent heel ulcers. Research is needed on
      the effects of friction on the heel during the transfer and movement of surgical
      patients. DECLARATION OF INTEREST: This study was sponsored by Johnson & Johnson
      Medical.

PMID- 15517748
TI  - Psychological needs of patients when dressing a fungating wound: a literature
      review.

PMID- 15517749
TI  - Influence of dressing changes on wound temperature.
AB  - OBJECTIVE: When wound-tissue temperature falls below 33 degrees C neutrophil,
      fibroblast and epithelial cell activity decreases. This study examined the
      influence of dressing changes on wound temperature. METHOD: The wound-bed
      temperatures of patients with a wound resulting from trauma or surgical
      debridement were measured immediately before and after dressing changes using a
      DermaTemp infrared body surface scanning device. The temperature on the surface
      of the dressing product was measured immediately before the dressing change and
      then every five minutes it until the pre-procedural temperature was reached.
      RESULTS: A total of 133 dressing episodes were measured, yielding 266 wound-bed
      temperature measurements and 619 external dressing temperature measurements. Pre
      procedural temperatures showed that the wound beds were on average marginally
      below the 33 degrees C threshold immediately after dressing takedown (mean: 32.7
      degrees C). This figure dropped two degrees on average as a result of the
      dressing-change procedure (mean: 29.9 degrees C). Reapplied wound-dressing
      products return to the pre-procedural temperature within 30 minutes (mean: 23
      minutes). CONCLUSION: This study provides baseline data for future research aimed
      at promoting maintenance of a normothermic wound bed. DECLARATION OF INTEREST:
      None.

PMID- 15517750
TI  - Evaluation of SurePress Comfort: a new compression system for the management of
      venous leg ulcers.
AB  - OBJECTIVE: The primary aim was to compare the healing of venous leg ulcers after
      management with either a new compression stocking (SurePress Comfort, ConvaTec)
      or a standard short-stretch bandage system (Comprilan, BSN Medical GmbH & Co).
      Secondary parameters included healing rate, ease of application and removal,
      comfort during wear, local pain levels and concordance. METHOD: This was a
      prospective multicentre open-label comparative randomised controlled parallel
      group pilot trial of 12 weeks' duration. RESULTS: The proportion of ulcers that
      healed in 12 weeks (44.4% versus 17.2%, p=0.027) and the average time to healing
      (72 +/- 5 days versus 101 +/- 7 days, p=0.0265) were significantly better with
      SurePress Comfort than the comparator. All the secondary parameters (except
      concordance) also showed statistically significant differences for the stocking
      over the comparator. CONCLUSION: SurePress Comfort stocking system is more
      effective than a standard short-stretch compression bandage in healing venous leg
      ulcers and in reducing associated pain. It is well accepted by patients due to
      its ease of use and comfort, and its safety profile is comparable to that of a
      standard compression system. It may therefore provide an effective solution for
      the delivery of graduated compression and has the potential to improve
      concordance, compared with short- stretch bandages. DECLARATION OF INTEREST: This
      study was sponsored by ConvaTec.

PMID- 15517751
TI  - In-vitro testing of silver-containing dressings.

PMID- 15517753
TI  - CPR and pressure care.

PMID- 15517754
TI  - Is this leg ulcer venous? Unusual aetiologies of lower leg ulcers.

PMID- 15517755
TI  - Comparing cost per use of 3M Cavilon No Sting Barrier Film with zinc oxide oil in
      incontinent patients.
AB  - OBJECTIVE: This study compares the total cost of treatment, skin-condition
      management and prevention of skin breakdown of perianal/buttock skin in
      incontinent patients receiving 3M Cavilon No Sting Barrier Film (Cavilon NSBF)
      and zinc oxide oil. METHOD: This single-centre open-label prospective randomised
      study involved 40 patients with at least moderate skin damage resulting from
      incontinence. Patients were randomised to receive either zinc oxide oil or
      Cavilon NSBF and were treated for 14 days. The study products and other treatment
      related products used were recorded, as was the time needed to cleanse the
      application site and apply the product. RESULTS: Use of both products resulted in
      an improvement in skin condition after 14 days, but this was significantly better
      with Cavilon NSBF than zinc oxide oil. Cavilon NSBF was more cost-effective as
      fewer applications were required, less time was spent applying the skin barrier
      product and faster healing rates were achieved. The cost-effectiveness ratio per
      treatment group showed an improvement of one point in the total score of the skin
      assessment scale costs: 28.36 Euro for Cavilon NSBF versus 98.06 Euro for zinc
      oxide oil. CONCLUSION: Both products resulted in an improvement in skin condition
      after 14 days, but Cavilon NSBF was found to be more cost-effective. DECLARATION
      OF INTEREST: This study was supported by an educational grant from 3M.

PMID- 15517756
TI  - [Pulmonary hypertension--some problems resolved. More remain to be solved].
AB  - Pulmonary hypertension especially arterial and idiopathic is still a poorly
      understood disease often affecting young adults and leading to right ventricular
      overload, failure and death due to low cardiac output. Justification for new,
      aggressive, costly but effective methods of pharmacological and interventional
      treatment of pulmonary hypertension require precise, repeatedly performed
      prognostic assessment. This is currently provided not only by repeated right
      heart catheterization but mostly by exercise testing as well as non-invasive
      techniques such as echo-Doppler and biochemical myocyte markers including B-type
      natriuretic peptide and cardiac troponin. Such methods should allow better timing
      of atrial septostomy and listing for lung transplantation.

PMID- 15517757
TI  - [Value of spiral computed tomography in pulmonary hypertension].
AB  - Pulmonary hypertension (PH) represents an important diagnostic problem, because
      of its non-specific clinical presentation. AIMS OF THE STUDY: Estimation of
      sensitivity and specificity of spiral computed tomography (SCT) in diagnosis of
      PH. Estimation of the influence of the cause and character of PH on morphology of
      pulmonary arteries and right ventricle-pulmonary artery coupling. MATERIAL AND
      METHODS: 102 patients with clinical suspicion of acute pulmonary embolism (APE)
      or chronic PH (54F, av. age 51.3 +/- 17.3). Diameters of pulmonary arteries
      obtained in SCT, systolic pulmonary pressure calculated from the tricuspid
      gradient pressure, and indices of the right ventricle-pulmonary artery dynamical
      coupling (AcT) obtained from the echo-Doppler method were compared. RESULTS:
      Increased diameter (> 18 mm) of interlobar arteries was the most specific sign of
      PH (specificity 92%, sensitivity 45%). Diameter of proximal pulmonary arteries
      and pulmonary pressure was correlated in patients with APE (r = 0.487, p <
      0.003), but not in those with chronic PH (r = 0.223). In a group of patients with
      pulmonary arterial hypertension (PAH), enlargement of proximal pulmonary arteries
      seemed to result in less disturbed right ventricle-pulmonary artery dynamic
      coupling. CONCLUSIONS: 1. SCT measurements of diameters of pulmonary arteries
      have relatively low sensitivity for PH, precluding its reliable exclusion. 2. The
      relationship between the pulmonary pressure and the diameters of pulmonary
      arteries was found in acute but not in chronic PH, in which right ventricle
      pulmonary artery dynamical coupling seemed less disturbed when pulmonary arteries
      were markedly dilated.

PMID- 15517758
TI  - [Inhaled nitric oxide (NO) for vasoreactivity testing in pulmonary hypertension].
AB  - Thirty patients (24F, 6M, aged 40.5 +/- 15.4 years) with chronic precapillary
      pulmonary hypertension (primary pulmonary hypertension--PPH)--20 pts, associated
      with connective tissue disease--6 pts, due to thromboembolism--2 pts and
      Eisenmenger syndrome--2 pts) were submitted to 5 min inhalation of 10 and 20 ppm
      of nitric oxide (NO) during right heart catheterization. For the whole group this
      test resulted in minimal changes in directly assessed hemodynamics. However,
      individual reactions differed markedly between patients. Assuming three levels of
      criteria of preserved reactivity (liberal, standard, demanding) 11/30 (37%)
      patients had fall in PAP and PVR > or = 20% from baseline, 4/30 (13%) decreased
      PAP and PVR by > or = 20% and 30% respectively and 2 (7%) patients normalized PAP
      and decreased PVR > or = 50% from baseline, respectively. Interestingly, even
      liberal criteria were fulfilled positive test was observed exclusively in
      patients with primary PH. In one patient with connective tissue disease and
      systemic hypertension acute pulmonary congestion appeared during NO testing, with
      concomitant increase in systemic arterial pressure and pulmonary wedge pressure.
      No other complications were noted and no rebound PH after discontinuation of NO
      was observed in any of the patients. CONCLUSION: 1. Acute inhaled nitric oxide
      test appears to be safe in patients with PH and no coexisting left heart
      dysfunction. 2. It allows for stratification of patients according to the degree
      of preserved pulmonary vascular reactivity. However, criteria which would permit
      to select optimal treatment based on the results of NO test require further
      studies.

PMID- 15517759
TI  - [Pulmonary hypertension in patients with pure obstructive sleep apnea].
AB  - Patients with obstructive sleep apnoea (OSA) every night experience recurrent
      episodes of alveolar hypoxia. Alveolar hypoxia is the most potent pulmonary
      vasoconstrictor causing remodeling of pulmonary arteries and pulmonary
      hypertension. Development of pulmonary hypertension in patients with OSA is
      rather rarely observed but still discussed. We studied pulmonary haemodynamics,
      using Swan Ganz thermodilution catheter, in 67 patients (64 M and 3 F, mean age
      45 years) with severe OSA (in full polysomnography mean AHI = 62) and normal
      pulmonary function data. We observed normal mean haemodynamic values at rest: PPA
      15,8 mm Hg, PW 6.8 mm Hg, CO 5.6 L/min. PVR 150 dyn.sec.cm(-5). In 11 pts (16%)
      the pulmonary artery pressure at rest was elevated (PPA 23.9 mm Hg and PVR 234
      dyn.sec.cm(-5)), they were younger, more obese and had higher number of apneic
      episodes per hour of sleep. During mild exercise (44 pts) PPA rose from 15.8 mm
      Hg to 29.8 mm Hg and was abnormally high in 17 pts. IN CONCLUSION: we observed
      pulmonary hypertension at rest in 16% patients with severe OSA, but during
      exercise in about 40%.

PMID- 15517760
TI  - [Right ventricle structure and function in patients with obstructive sleep apnea
      (OSA)].
AB  - The structure and function of right ventricle was echocardiographically assessed
      in patients (pts) with OSA and analyzed taking into account the presence of
      obesity and/or systemic hypertension (SH). Therefore, 118 pts (98 M, 20 F, aged
      48,5 8,4 yr) were divided into OH = obese with z OSA and SH (n = 22), ON = obese
      with OSA, and no SH (n = 20), OC = OSA without either obesity and SH (n = 21), GH
      = obese without OSA but with SH (n = 18), GN = obese without either OSA or SH (n
      =17). Control group (ZZ) comprised 20 healthy subjects (14M,6F). Right
      ventricular diameter (RVD), diastolic (DRVW), and systolic right ventricle free
      wall thickness (SRVW) were measured and its systolic thickening (ST-RVW) was
      calculated. Acceleration time of ejection into pulmonary artery (AcT) was
      measured with Doppler echocardiography. RESULTS: St. sign. p < 0.05 between: 1:
      all groups except OH and ON, GH and GN, GH and OC, GN and OC; 2--like 1 except ZZ
      and OC; 3--OH and all subgroup except ON, ON and GH, ON and ZZ, OC and GN; 4-- ON
      and all subgroups except OH, OH and OC, OH and GH, OH and GN. CONCLUSIONS:
      Enlargement and functionally compromised RV is found in OBS mostly with
      concomitant obesity. Pulmonary hypertension at rest in patients with isolated OSA
      is rare and also requires additional contributing factors.

PMID- 15517761
TI  - [Effect of localization of pulmonary arterial changes on echocardiographic
      indices of right heart function and their correlation with exercise capacity:
      comparison of arterial and thromboembolic pulmonary hypertension].
AB  - AIM: To assess correlation between exercise tolerance and Doppler-derived indices
      of right ventricular (RV)--pulmonary arterial coupling in patients with different
      location of vascular lesions causing pulmonary hypertension (PH). MATERIAL: 45
      patients: 21 with thromboembolic (TE-PH) and 24 with arterial PH defined as
      systolic pulmonary arterial pressure (SPAP) > 40 mm Hg. The two groups were
      similar as far as SPAP (74,8 +/- 15,2 vs 76.5 +/- 14,1 mm Hg, p = ns) and
      distance covered during 6 minute walk test (339 +/- 116 vs 320 +/- 127, p = ns)
      are concerned. RESULTS: Flow velocity curve in the RV outflow tract were
      different in the two groups. Time from onset to peak velocity of ejection
      (acceleration time, AcT) as well as to midsystolic deceleration were shorter in
      TE-PH then in arterial PH (59.0 +/- 6.3 vs 68.1 +/- 15.4 msec, p = 0.015 and
      123.8 +/- 17.9 vs 137.9 +/- 29.7 msec, p = 0.071, respectively). In the whole
      studied group as well as in arterial PH significant correlation between exercise
      tolerance and Doppler-derived indices of RV--pulmonary arterial coupling were
      found (r = 0.51, p < 0.001 and r = 0.72, p = < 0.001, respectively).
      Interestingly, no such relationship was found in TE-PH, (r = 0.16, p = ns).
      CONCLUSION: In contrast to arterial PH, pressure wave prematurely reflected from
      the intraluminal thrombi seem to disturb the RV ejection pattern and its
      correlation with exercise tolerance in TE-PH. Whether progression or effects of
      treatment on arterial PH can be assessed by monitoring changes in Doppler-derived
      indices of RV--pulmonary arterial coupling requires further studies.

PMID- 15517762
TI  - [Effect of long-term therapy with oral Beraprost on survival of patients with
      arterial and inoperable thromboembolic pulmonary hypertension].
AB  - Beraprost sodium (BPS)--an orally active prostacyclin analogue--improves
      haemodynamic parameters and quality of life in group of patients with pulmonary
      arterial hypertension. Effect of long-term therapy with BPS is not well defined.
      This study assesses influence of long-term therapy with BPS on the survival of
      patients with precapillary pulmonary hypertension. Studied group consisted of 25
      patients with precapillary PH (18 F, 7M, aged 34 +/- 13,9 years). Sixteen
      patients were diagnosed with primary PH, 3 pts had PH associated with connective
      tissue disease, 5 pts developed PH in course of congenital systemic to pulmonary
      shunt, and 1 patient suffered from inoperable chronic thromboembolic PH. At time
      of diagnosis 15 pts presented exercise impairment of WHO class II and 10 pts were
      in functional class III. All studied subjects had complete hemodynamic assessment
      of right heart and obtained values were used for estimation of hypothetic
      survival using prognostic equation proposed by D'Alonzo et al. On follow-up
      period patients received BPS in the highest tolerated dose (80-480 mg daily).
      During a follow-up period (mean: 22 months) 7 patients died. Cumulative survival
      rate BPS group was significantly higher in BPS group comparing to hypothetical
      survival at 6 months (96% (95% CI: 88-104%) vs 73% (95% CI: 67-78%), p = 0.02)
      and 12 months (94% (95% CI: 84-104%) vs 65% (58-71%), p = 0.01), respectively. At
      18 and 24 months differences between BPS virtual and hypothetical survival were
      not statistically significant. There was no correlation between survival and
      maximal achieved dose of BPS. These results suggest, that BPS improves prognosis
      of patients with precapillary PH during 12 months after initiation of therapy.
      Later effect of BPS seems to decrease, requiring changing or intensification of
      therapy.

PMID- 15517763
TI  - [Pulmonary thrombendarterectomy in a patient with chronic thromboembolic
      pulmonary hypertension (CTEPH) and chronic renal failure due to diabetic
      nephropathy--case report].
AB  - A case of 63-years old man suffering from CTEPH and chronic renal failure due to
      diabetic nephropathy is presented. First diagnosis of pulmonary hypertension was
      made at the beginning of 2000. Then the secondary anticoagulant prophylaxis were
      introduced. Despite such treatment there was no improvement and level of
      pulmonary hypertension increased. Finally, the pulmonary thrombectomy was
      considered because of proximal location of thromboembolic obstruction in
      pulmonary artery. Before surgery, the hemodialysis was started. Pulmonary
      thrombendarterectomy along with right coronary artery bypass grafting were
      performed in November 2001. The procedure was conducted successfully. The
      patient's condition improved and pulmonary pressure dropped substantially. During
      follow-up anticoagulant prophylaxis and hemodialysis are continued. It might be
      conducted that pulmonary thrombendarterectomy can be successfully performed also
      in patients with complex coexisting conditions.

PMID- 15517764
TI  - [Scimitar syndrome--case report].
AB  - Scimitar syndrome is a rare congenital anomaly. This syndrome is characterized by
      partial or complete anomalous pulmonary venous drainage of the right lung to the
      inferior vena cava. There is a characteristic abnormal radiographic shadow which
      descends along the right cardiac border (scimitar sign). We examined 71-year old
      woman with severe pulmonary hypertension due to a large shunt between pulmonary
      veins and right atrium. Other cause of pulmonary hypertension is atrial septum
      defect. Our patient required permanent pacemaker implantation for tachy-brady
      syndrome.

PMID- 15517765
TI  - [Clinical use of NO inhalation].

PMID- 15517766
TI  - [Genetics of primary pulmonary hypertension].

PMID- 15517767
TI  - [Lung transplantation for end-stage pulmonary hypertension].

PMID- 15517768
TI  - [Pregnancy, labor and puerperium in patients with HELLP syndrome].
AB  - OBJECTIVE: The aim of this study was to evaluate retrospectively 10 women with
      the syndrome of hemolysis, elevated liver enzymes, low platelets (HELLP)--age of
      patients, quality of antepartum medical care, clinical, biochemical parameters,
      treatment, course and duration of pregnancies, way of delivery, and puerperium.
      MATERIAL AND METHODS: Women in the study group were divided in order of platelets
      (PLT) levels: 4 patients with PLT levels lower than 50 G/l and 6 patients with
      PLT levels higher than 50 G/l. The mean duration of pregnancies in both groups
      was similar. RESULTS: In the first group just one women delivered by vaginal
      route when compared with the cesarean delivery. We noticed lower frequency of
      antepartum medical visits among the first group. Such signs as vomiting, nausea,
      abdominal pain, pruritus occurred more frequently in the second group. The most
      common complication observed in both groups of patients was severe preeclampsia.
      HELLP syndrome was also observed in the multiple pregnancies. In the study group
      high blood concentrations of urea, creatinine, total bilirubin, alanine
      transaminase and aspartate aminotransferase were present. Termination of
      pregnancy is still recognised to be the best way of HELLP treatment, however the
      efficacy of steroid drugs administration as conservative treatment were also
      demonstrated. CONCLUSION: The disseminated intravascular coagulation as the HELLP
      complication in the puerperium period seems to be a serious problem, which can
      conduct to the need of hysterectomy.

PMID- 15517769
TI  - [Obstetric hysterectomy--analysis of indications in years 1992-2001].
AB  - AIM OF THE STUDY: Analysis of indications and post-operative course in patients
      after obstetric hysterectomy. MATERIAL AND METHODS: 45 cases of obstetric
      hysterectomy were analysed. RESULTS: Mean age of operated woman was 32.18 +/-
      4.31 years. Mean gestational age was 35.9 +/- 1.76 weeks. The estimated rate of
      obstetric hysterectomy was 2.5 per 1000 deliveries. The most frequent indication
      for urgent hysterectomy were placentation disorders. Elective hysterectomy was
      performed because o invasive cervical cancer and uterine myomas. Mean time of
      duration of surgery was 91.67 min. CONCLUSIONS: 1. Indications for obstetric
      hysterectomy should be stated very carefully and the operation should be
      performed by the most experienced staff. 2. In case of severe intraoperative
      bleeding internal iliac artery ligation should be performed.

PMID- 15517770
TI  - [Ultrasonographic diagnosis of cervical incompetence].
AB  - OBJECTIVE: The aim of this study was to verify clinical diagnosis of cervical
      incompetence by the use of transvaginal sonography. MATERIAL AND METHODS: 101
      pregnant women hospitalized at the Pathological Pregnancy Department, Medical
      University of Lodz in years 2000-2002 because of suspicion of cervical
      incompetence were analysed. The mean age of examined group was 24 +/- 3.24 yr.
      All pregnant women underwent ultrasound cervical assessment at the 18-30 week of
      gestation by using Hitachi EUB 515C system. Sonographic measurements of cervical
      length and width were performed. The cervical length below 30 mm and width at
      least 6 mm were sonographic criteria of cervical incompetence. RESULTS: In 63
      pregnant women cervical incompetence was not confirmed by ultrasound examination.
      In 38 patients sonographic features of cervical incompetence were established. 38
      pregnant women were underwent elective cervical cerclage for cervical
      incompetence. Because of poor previous history 8 women with normal ultrasound
      examination were treated by cervical cerclage. CONCLUSIONS: We conclude, that
      clinical diagnosis of cervical incompetence should be verified by the use of
      transvaginal sonography to provide an objective diagnosis.

PMID- 15517771
TI  - [Prognostic significance of AgNORs expression in endometrial cancer].
AB  - OBJECTIVES: The purpose of the study was assessing prognostic value of AgNORs
      expression in endometrial cancer. MATERIALS AND METHODS: The study was performed
      in a group of 90 patients, diagnosed with endometrial cancer, treated in Clinic
      of Gynecological Oncology in Wroclaw. Silver nucleolar organizer regions (AgNORs)
      were stained in paraffin-embedded samples, using Ploton method modified by
      Oefner. RESULTS: The mean number of AgNORs was 2.76 +/- 0.46. To assess the
      possible influence of AgNORs expression, patients were divided into three groups,
      based on the mean number of AgNORs: I- <2.3; II- 2.3-3; III- >3. The differences
      in the outcome between these groups were not significantly different. The mean
      number of AgNORs in the group of patients with distant metastases and progression
      did not differ (2.72). The highest mean number of AgNORs (3.38) was observed in
      patients with local failure. CONCLUSIONS: At this point in time, there is
      inadequate evidence to use AgNORs as predictive factors in patients with
      endometrial cancer further studies are warranted.

PMID- 15517772
TI  - [Decrease of paraoxonase activity in the first day after abdominal operations in
      women].
AB  - INTRODUCTION: Paraoxonase (PON1) is one of enzymes participating in antioxidative
      defence mechanism, which protects the organism from the results of action of
      reactive oxygen species. PON1 is an esterase contained in plasma high density
      lipoproteins (HDL) which protects HDL from peroxidation and plasma membranes from
      free radical injury. PON1 serum activity is diminished in some diseases
      (atherosclerosis, diabetes, coronary artery disease) and after cardiosurgery
      operations. But there is no information about changes in PON1 activity after
      abdominal operations. THE AIM: Of this study was the assessment of PON1 serum
      activity after the abdominal operations in women. MATERIALS AND METHODS: 40 women
      operated in the 1st Department of Gynaecology of Lublin Medical University were
      studied, including 34 patients after total abdominal hysterectomy with salpingo
      oophorectomy and 6 patients after myomectomy or cyst enucleation. The blood to
      experiments was collected before operation, and 8 and 24 hours after. PON1 serum
      activity was assessed spectrophotometrically toward two synthetic substrates:
      paraoxon and phenyl acetate. RESULTS: PON1 activity toward paraoxon before
      operation was 146.8 +/- 17.3 U/ml, and after 8 and 24 hours after 107.6 +/- 11.9
      U/ml and 119.9 +/- 16.9 U/ml, respectively (results statistically significant).
      PON1 activity toward phenyl acetate (arylesterase activity) before operation was
      182.7 +/- 16.4 U/ml and did not significantly changed after the surgery.
      CONCLUSION: It is observed decreased PON1 serum activity in the early
      postoperative period after abdominal operations in women, what can be connected
      with the utilisation of PON1 in antioxidative defence mechanism.

PMID- 15517773
TI  - [Fertility of women after conservative operation for borderline ovarian tumors].
AB  - OBJECTIVES: The aim of the study was to assess procreation in group of patients
      who were treated by conservative operation for borderline tumors of the ovary.
      DESIGN: The analysis included 42 patients conservatively operated for ovarian
      tumor of borderline malignancy in Department of Gynecology Medical University of
      Gdansk between 1978-2000. The incidence of pregnancy, age of patients, tumor
      pathology, type of conservative surgery and the course of pregnancy and labour
      were evaluated in this study. RESULTS: In the analysis group were 36 (85.7%)
      stage IA, 2 (4.8%) stage IB, 3 (7.1%) stage IC and 1 (2.4%) stage III C patients.
      Unilateral adnexectomy was performed in 36 (85.7%) patients, 4 (9.5%) unilateral
      cystectomy, 2 (4.8%) bilateral cystectomy with omentectomy in one case. After
      conservative operation 10 (23.8%) patients were pregnant and delivered healthy
      children but 2 patients delivered twice and 1 third. Recurrence was observed in 2
      patients in period of 27 and 50 months after operation. 5 years survival was
      97.6%. CONCLUSIONS: Percentage of pregnancy after conservative treatment for
      borderline ovarian tumors was high (23,8%) and number of recurrences was low so
      conservative surgery allows young women to retain procreational potential without
      increasing risk of recurrence.

PMID- 15517774
TI  - [Life style, Chlamydia trachomatis infection, bacterial vaginosis and their
      impact on the frequency of cervical lesions].
AB  - OBJECTIVES: Sexually transmitted infectious factors attained unquestionable
      importance in the initiation of the cervical intraepithelial neoplasia. The aim
      of this study was to evaluate the incidence and impact of Bacterial vaginosis,
      Chlamydia trachomatis infection in accordance to a life style on clinically and
      cytologically evaluated cervical lesions. DESIGN/METHODS: Seventy-two young women
      without any symptoms were included to the study. Women underwent pelvic
      examination when cervical smears for cytology and Ch.tr. were taken and BV tests
      were performed. Presence of Chlamydia was estimated by direct immunofluorescent
      method. Subjects included to the study provided information concerning life
      style, and gynecological complaints. RESULTS: In both BV(+) or Ch.tr.(+) women,
      abnormal PapTest results were more frequently observed. All those three factors
      correlated with declared over 5 lifetime sexual partners. Ch.tr. infection
      correlated with BC pills using, cigarette smoking and presence of the cervical
      lesions evaluated as glandular ectopy. Abnormal PapTest result was obtained in 12
      subjects. Two, the most abnormal cases were described as LSIL and confirmed by
      direct biopsy as CIN 1, also with coexistence of C. trachomatis infection and
      positive for BV. CONCLUSIONS: Ch.tr. infection seems to affect more frequently
      sexually active, smoking, young women using BC pills, with presence of cervical
      lesion described as clinically unsuspected glandular ectopy, although with
      occasionally cytological abnormal findings.

PMID- 15517775
TI  - [Large mesenteric cyst in a patient suspected of ovarian cyst].
AB  - Mesenteric cystic tumors are very rare. They may simulate the ovarian cysts. We
      report a case of a 38 year-old woman with large cystic tumor suggesting ovarian
      cyst. The patient was operated on and we found that genital organs were normal.
      Besides there was a large cyst of small intestine mesentery with 10 liters of
      clear fluid. The cyst was removed. Histological material showed mucinous
      cystadenoma.

PMID- 15517776
TI  - [Vesicouterine fistula as a complication after previous cesarean section 18 years
      earlier].
AB  - A case of vesicouterine fistula diagnosed in 40-year old woman who underwent
      cesarean section 18 years earlier was presented. The clinical features, etiologic
      factors, diagnostic procedures and treatment modalities were discussed in
      relation to the case and others reported in the literature. The gift of contrast
      by catheter to bladder allowed to visualize the fistula.

PMID- 15517777
TI  - [Immuno-physiology of normal pregnancy. Part II. Immunoregulatory mechanisms of
      placental origin and systemic immunological response].
AB  - Contemporary opinions concerning the role of placenta as well as systemic
      immunological response in normal pregnancy were presented in the paper. Special
      attention was paid to the importance of HLA-G antigens, changes of peripheral
      blood cellular immunological response and blocking antibodies.

PMID- 15517778
TI  - [Biologic tissue response to sutures].
AB  - The search for the ideal suture material has continued for decades. Implantation
      of foreign materials, including surgical sutures causes cellular response. Use of
      materials of natural origin is connected with a more pronounced reaction than
      that caused by synthetic sutures. The above review summarizes properties of
      suture materials that may be useful for choosing indication of the appropriate
      material in varying surgical situations.

PMID- 15517779
TI  - [Significance of alpha1-antichymotrypsin (ACT) in early diagnosis of intra
      amniotic infection (IAI)].
AB  - The aim of the present study was to determine the level and pattern of alpha1
      antichymotrypsin (ACT) in women with intra-amniotic infection (IAI). The ACT
      level was determined using rocket immunoelectrophoresis according to Laurell. In
      determining of ACT isoform level the crossed immunoelectrophoresis method by Bog
      Hansen was used. In our study the ACT level was statistically higher in the IAI
      group if compared to the group of healthy pregnant women. We have also observed
      the higher level of A4 isoform of ACT in the group with IAI if compared to the
      controls. We have concluded that ACT A4 isoform could be the good marker in early
      detection of IAI.

PMID- 15517780
TI  - [Prognostic value of ultrasonography of the yolk sac in singleton pregnancy].
AB  - OBJECTIVES: The aim of the research was evaluation of the clinical usefulness of
      chosen ultrasonographic morphological parameters of the yolk sac in the first
      trimester of unifetal pregnancies. MATERIAL AND METHOD: Analysis has been done on
      391 cases of unifetal pregnancies in the first trimester. Parameters of
      ultrasonographic evaluation: diameter, appearance and size of yolk sac,
      biometrics and fetal anatomy, confirmation of heart beating. CONCLUSIONS: The
      yolk sac should be observed in the fifth week or when its biggest size equals to
      10 mm in a normal pregnancy. Abnormal morphological appearance of the yolk sac
      and/or the size over 9 mm suggest serious growth disorders of the fetus or its
      necrobiosis. The yolk sac, apart from cases of hydatid mole, should be possible
      to be observed between 5-12 weeks of pregnancy.

PMID- 15517781
TI  - [Newborn of a mother with HELLP syndrome].
AB  - HELLP syndrome is a serious complication of pregnancy with characteristic
      appearances between 22 to 26 weeks of gestation. Clinical classification in three
      groups, is based on platelet count. Early diagnosis and appropriate management
      allow women to achieve a mortality rate below 1%. Neonatal complications are
      strongly associated with a newborn's immaturity and class of HELLP syndrome. In
      both presented cases despite identical maternal treatment (steroids because of I
      st class of HELLP syndrome) neonatal clinical courses were different due to the
      differences in gestational age. However, appropriate prenatal and neonatal care
      in tertiary centers was successful.

PMID- 15517782
TI  - [Thrombin markers in pregnant women: measurements of prothrombin fragments F 1+2
      and thrombin-antithrombin III complexes (TAT) in the cord blood, the mother's
      blood and in amniotic fluid].
AB  - OBJECTIVES: Hypercoagulability is a well known feature of pregnancy, while
      hypocoagulability is attributed to newborns. The level of thrombin markers in the
      blood reflects the relations in coagulation system. We have measured two markers
      of thrombin generation, e.i prothrombin fragments F 1+2 and thrombin-antithrombin
      III complexes (TAT), in the cord blood and the mother's blood, as well as in
      amniotic fluid. MATERIAL AND METHODS: The study group consisted of 33 parturient
      women, 24.2 +/- 3.6 years old, 20 primiparas and 13 multiparas with normal course
      of pregnancy. The level of F 1+2 and the level of TAT were estimated by ELISA
      method. RESULTS: The highest level of F 1+2 and TAT was in amniotic fluid, e.i.
      29.99 (9.15 - 50.75) nmol/l vs. 519.62 +/- 270.51 microg/l. In the blood cord the
      level of F 1+2 was 7.15 (5.05 - 22.05) nmol/l, and the level of TAT was 151.57 +/
      134.17 microg/l. In the mother's blood plasma the levels of F 1+2 and TAT were
      significantly lower than in cord blood (5.15, range 3.50 - 6.05 nmol/l vs. 36.30
      +/- 18.65 microg/l respectively, p < 0.001). CONCLUSION: Increased generation of
      thrombin in foetal blood which is reflected in increased levels of F 1+2 and TAT,
      is one of the features of "foetal phenomenon" concerning foetal coagulation
      system. High concentration of F 1+2 and TAT in amniotic fluid can be consider to
      be a result of increased thrombin generation or the lowered metabolism of F 1+2
      and TAT.

PMID- 15517783
TI  - [Genetic amniocentesis in the II Department of Obstetrics and Gynecology of the
      Medical University of Warsaw].
AB  - OBJECTIVE: Characteristic of patients, indications, outcomes and complications of
      genetic amniocentesis. MATERIAL AND METHODS: Retrospective analysis of 420 women
      who underwent genetics amniocentesis from January 1999 to 2001. It was done by
      ultrasound-guided insertion of a 22-gauge needle from 12 to 19 week's gestation.
      From 9 ml to 24 ml of amniotic fluid were removed for cytogenic analysis.
      RESULTS: The mean maternal age was 37.6 +/- 4 years. The mean gestational age of
      amniocentesis was 14.2 +/- 1.2 weeks. 416 (99%) women were in singleton
      pregnancy, 3 (0.7%) in twin pregnancy and one (0.2%) in triplet pregnancy. The
      most common indication for amniocentesis was maternal age over 35 years (366
      cases - 87%). Chromosomal abnormalities were identified in 23 cases (5.5%). Any
      neural tube defects were observed. In 6 (1.4%) cases the cell culture of amniotic
      fluid was unsuccessful and procedure was repeated. 2 (0.4%) women lost pregnancy
      during 7 days after procedure. 4 patients (0.9%) had amniotic fluid leakage, of
      which no ended in fetal loss. 1 (0.2%) had pain in hypogastrium after
      amniocentesis, all delivered at term. CONCLUSIONS: The pregnancy loss rate in
      women who underwent genetics amniocentesis was 0.4%. The most common indication
      for genetic amniocentesis was maternal age over 35 years. Chromosomal
      abnormalities were detected in 5.4% of the fetuses.

PMID- 15517784
TI  - [Metabolic activity of peripheral blood neutrophils in women with ovarian
      tumours].
AB  - OBJECTIVES AND DESIGN: Neutrophils play important role in first line defence an
      they release soluble growth and chemotactic factors and guide the recruitment of
      non-specific immune effector cells. We estimated the activity and ability to
      reduce of nitroblue tetrazolium (NBT) by peripheral blood neutrophils in women
      with benign or malignant ovarian tumours. MATERIALS AND METHODS: The study was
      performed on 43 women between the ages of 19 and 72 with ovarian tumours.
      Cystadenoma serosum was diagnosed in 19 women, Cystadenocarcinoma serosum in 9,
      and teratoma adultum in 15 women. Venous blood samples were obtained prior to the
      operation. The control group consisted of 30 women their age range was from 22 to
      60 years. In peripheral blood samples from both groups; there leukocyte counts
      and total neutrophils were determined. Metabolic activity was investigated by
      nitroblue tetrazolium reduction spontaneous (NBTsp) test, and stimulation by
      latexs (NBTst) test. RESULTS: In women with ovarian tumours, the index of
      spontaneous NBT reduction turned out to be significantly higher than that in the
      control group (p<0.0001). In the group studied, the index of latex-stimulated NBT
      reduction was significantly lower than that in the control group (p<0.0001).
      CONCLUSIONS: Intensity oxidation-reduction changes of neutrophils in reduction
      NBT in women with ovarian tumours were observed.

PMID- 15517785
TI  - [Pre-pubic TVT in the treatment of urinary incontinence in women. Description of
      surgical technique and initial results].
AB  - Tension-free vaginal tape (TVT) has within the last decade become one of the most
      popular procedure for treatment of female urinary stress incontinence. It is
      still persistent the risk of complications peri- and postoperative in spite of
      high efficacy of this method. Investigators still have been looking for new
      variations of this method to diminish the risk of complications and to maintain
      the efficacy of the treatment. The aim of this study is the description of the
      pre pubic TVT method and the preliminary short time (3 month) results of
      treatment. The results of pre-pubic TVT treatment were compared with "classic"
      TVT method. The pre-pubic TVT technique was performed in 25 women, operated for
      stress incontinence. The average operation time was 19 min (10-30 min). During
      the operation in one of patients there was excessive bleeding from venous plexes
      of vagina during preparation of tissues and in 4 of them it was perforation of
      vaginal mucosa during introducing of needle with tape. All these complications
      were recognised and corrected during the surgery. The mean hospitalisation time
      was two days. Our 3-months observations allow to confirm that efficacy of pre
      pubic TVT is similar to the "classic" method, but the frequency of complications
      is lower in the pre-pubic TVT. There were no postoperative complications and
      voiding dysfunctions.

PMID- 15517787
TI  - [Aortocaval compression syndrome as an explanation of sudden intrauterine death
      of mature twins at term. Case report].
AB  - There is a description of a case of sudden intrauterine unexplained death (SIUD)
      of healthy twins at term. The course of the pregnancy was regular. There were no
      significant sinister symptoms of fetal impend. No malformations or other
      abnormalities were observed after delivery by cesarean section. The probable
      cause of SIUD seems to be aortic-vain syndrome.

PMID- 15517786
TI  - [Sexual initiation and use of condoms and other methods of contraception among 15
      year-old adolescents in Poland and other countries].
AB  - OBJECTIVE:  PRESENTATION: (1) Frequency of sexual initiation and use of condoms
      and other methods of contraception among 15-year old adolescents in Poland and
      other countries in 2001/2002; (2) Trends of change in these sexual behaviours in
      Poland between 1990-2002. MATERIAL AND METHOD: Representative samples of
      adolescents in Poland (mean age 15.7 years) in 1990 (N=1548), 1994 (N=1540), 1998
      (N=1638) and 2002 (N=2152) and in other 28 countries (mean age 15.2 - 16.1 years)
      in 2001/2002, were used. The surveys were carried out in the frame of Health
      Behaviour in School-Aged Children; a WHO Collaborative Cross-National Study
      (HBSC), according to an international research protocol. An international
      standard questionnaire (anonymous) was chosen as an instrument for data
      collection. It contained four questions concerning sexual behaviour. RESULTS: In
      Poland, 2002, 20.9% of boys and 9.2% of girls reported sexual intercourse with
      mean ages respectively 14.1 and 14.7 years. The frequency of sexual initiation
      was higher (in boys) and the mean age was lower among adolescents living in towns
      by comparison to those living in cities. More matured adolescents had earlier
      sexual initiations. 27% of sexually active adolescents reported that either they
      or their partners had used any methods of contraception during their last sexual
      encounter. This risk sexual behaviour was more frequent in than cities
      (respectively: in boys 30.2% and 23.9%; in girls 42.9% and 19.7%). The most
      common method used was a condom. Between 1990-1998, the percentage of adolescents
      having sex and using some methods of contraception during their encounter last
      sexual were observed. Between 1998-2002, frequency of sexual initiation
      decreased, whereas percentage of non-users increased. In comparison to other
      countries increased Poland's percentage of adolescents with early sexual
      initiation in 2001/2002 was low, but the percentage of non-users of
      contraceptives was the highest. CONCLUSIONS: At risk sexual behaviours are
      relatively common among 15-year-old adolescents, and more frequent among
      adolescents living in cities. In comparison to other countries, Polish
      adolescents the risk of unplanned pregnancies and sexually transmitted diseases
      is higher. Future monitoring of sexual behaviours is necessary for prevention
      (including school sexual education) of at risk behaviours.

PMID- 15517788
TI  - [Guillain-Barre syndrome during CMV infection complicating twin pregnancy--a case
      report].
AB  - A rare case of Guillain-Barre syndrome in the course of an acute CMV infection
      during twin pregnancy was reported. A clinical picture, diagnostic procedure and
      therapeutic management of CMV infection and its complications were presented. The
      reported case indicates that CMV infections should be taken into account in
      differential diagnosis in pregnant women with unclear neurological symptoms.

PMID- 15517789
TI  - [Problems of recurrent loss of pregnancy: are procoagulant microparticles a risk
      factor for pregnancy outcome?].
AB  - BACKGROUND: Circulating procoagulant microparticles (PM) are a novel risk factor
      for pregnancy outcome. They derive from cytosol and membranes of the cells
      undergoing apoptosis or pathological activation. Tissue factor and phospholipids
      are the active components of PM responsible for "placental thrombosis" and
      pregnancy loss. STUDY DESIGN: The paper is a survey of the literature on the
      pathological role of PM in complicated pregnancy. RESULTS AND CONCLUSIONS: The
      published studies suggest that PM play a role of a pathogenic factor in women
      with repeated pregnancy loss. Prophylaxis within low-molecular heparin is a
      promising clinical procedure.

PMID- 15517790
TI  - [Angiogenesis in the female reproductive processes].
AB  - Angiogenesis or the formation of new vessels out of pre-existing capillaries is a
      sequence of events that is fundamental to physiology of the female reproductive
      tract and also pathologic processes such as ovarian hyperstimulation syndrome.
      Many factors include vascular endothelial growth factor (VEGF), angiopoietins and
      others involved in the regulation of angiogenesis have been identified. There are
      some endocrine control mechanisms, which stimulate or inhibit the angiogenesis.
      The studies indicate that the normal processes of folliculogenesis, ovulation and
      corpus luteum function in the ovary and the control of menstruation and
      implantation in the endometrium are profoundly dependent on the angiogenesis. The
      rapid, controlled and cyclical nature of angiogenesis in the female reproductive
      tract suggests that interference with this process should provide a novel
      approach to manipulation of reproductive function.

PMID- 15517792
TI  - ["Nadine Hesnart, "an anticipated victory". Interview by Helene Delmotte].

PMID- 15517793
TI  - [Conquering cystic fibrosis: reasons to get angry].

PMID- 15517796
TI  - [Cancer in children today].

PMID- 15517797
TI  - [Psychopathological aspects of cancer in children].

PMID- 15517798
TI  - [Secrets of a successful nurse/nurse's aide collaboration].

PMID- 15517800
TI  - [Emergency nurses for firefighters, focus on a new profession. Interview by
      Helene Delmotte].

PMID- 15517801
TI  - [Inserting art into the hospital].

PMID- 15517802
TI  - [The kiss].

PMID- 15517803
TI  - [Methylphenidate. A possibility for rare hyperactive children].

PMID- 15517804
TI  - [Hospitalization of children. The parents, visitors like no other. Interview by
      Marie-France Guerel].

PMID- 15517805
TI  - [Epidemiology of nosocomial bloodstream infections in Polish hospitals].
AB  - The article is devoted to the analysis of morbidity, mortality, risk factors and
      etiology of nosocomial bloodstream infections in Poland. The analysis was based
      on nationwide data collected in nosocomial infections surveillance system co
      coordinated by the Polish Society of Hospital Infections in 1999 in 120
      hospitals. There were 513,807 patients included in the study, among whom 11,157
      cases of nosocomial infections were detected. In this group 332 cases of
      nosocomial bloodstream infections (BSI) were detected, from this number 187 was
      the only detected site of infection (the rate of this infection was 1.9%). The
      highest mortality connected with BSI was observed among newborn children and in
      intensive care units (morbidity rate was 28.7 for 1,000 admissions). Mortality
      attributable to BSI was 9.1% among all BSI cases. The results of the analysis
      show that there is a statistically important increase of morbidity and mortality
      rates attributable to BSI among patients with vascular catheters in comparison to
      general population. There was also a detailed analysis of connection between the
      weight of newborn children and occurrence of BSI. In almost 80% of detected cases
      of BSI laboratory tests were performed in order to identify the etiological
      factor. According to the results of these tests dominant etiological factors
      were: Staphylococcus aureus (19.6%) from which almost 60% were MRSA, CNS (19.2%)
      from which about 10% were strains resistant to teicoplanin and Klebsiella spp.
      (15.7%) from which 60.4% were strains resistant to ceftazidime. There was also a
      separate analysis of etiological factors of BSI and their resistance to
      antibiotics among children.

PMID- 15517806
TI  - [Assessment of the occurrence and basic determinants of hepatitis C virus (HCV)
      infection among medical students in Silesian voivodeship].
AB  - HCV infection may result in serious health consequences such as chronic hepatitis
      C and liver cancer. In Poland, the data on the prevalence of HCV infection is
      limited and available information suggests an increased risk among young males.
      The aim of the study was to assess the prevalence of hepatitis C virus (HCV)
      infection between medical and non medical students, and to explore probable
      routes of HCV transmission. The project was conducted as a cross-sectional study.
      The study group included medical students (IV, V and VI year) and non medical
      students as a control group. The subjects were examined in the period from
      November 2002 to January 2003, (study group: n = 221; control group: n = 129).
      Serum samples were tested for antibody to HCV by ELISA method and anti-HCV
      positive samples were verified using Western Blot Line technique. Probable routes
      of infection were assessed by questionnaire. Preliminary results obtained in 29%
      of the target group suggested, that the prevalence of positive anti-HCV among
      students was 2.6% (95% PU: 1.2%-4.8%). It was higher among non medical than
      medical students (4.7% vs 1.4%). Anti-hepatitis C virus seropositivity was
      associated with a history of hepatitis. Verification of 9 positive anti-HCV cases
      proved only 1 HCV infection. Results presented in this paper are preliminary and
      will be verified after obtaining data for 600 medical students and for 600
      subjects in the control group.

PMID- 15517807
TI  - [Tick-borne encephalitis (TBE) cases in Bialostocki and Podlaski regions in years
      1993-2002].
AB  - TBE virus remains one of major etiologic agents of encephalitis in Poland. In the
      beginning of 90-ties great increase of TBE cases was observed. In the years 1993
      2002 there were TBE 1966 cases reported in Poland, while in
      bialostockie/podlaskie voivodeship there were 871 cases. In years 1993 and 1996
      111 TBE cases annually were reported in this region. The highest TBE incidence in
      this region was registered in years 1993 and 1996 - 15.9 and the lowest in 2001 -
      3.4. In analyzed period of time mean TBE incidence in Poland varied from 0.69 to
      0.26. TBE cases from bialostockie voivodeship from years 1993-1998 stated 43% of
      all cases in Poland and from podlaskie voivodeship from years 1999-2002 states
      46% of all.

PMID- 15517809
TI  - [Human granulocytic ehrlichiosis co-incident with Lyme borreliosis in pregnant
      woman--a case study].
AB  - A case of 25 years old woman, living in an endemic area for Lyme borreliosis was
      examined. In 29 th week of pregnancy thrombocytopenia, fever and fatigue were
      observed, in the last 7 weeks erythema migrans was present. The woman was not
      treated by that time. The infant presented thrombocytopenia in the first few
      weeks of life. 3 months after delivery erythema migrans disseminata was observed,
      by that time Lyme borreliosis and HGE were serologically confirmed. It was not
      confirmed that the infection was transferred to the infant, but it is possible
      that thrombocytopenia was caused by the infection with A. phagocytophila.

PMID- 15517808
TI  - [Exposure to ticks and erythema chronicum migrans among borreliosis patients in
      Lower Silesia].
AB  - The aim of the study was the analysis of Lyme borreliosis cases notified by
      Clinic for Infections Diseases in Wroclaw in connection with exposure to ticks in
      year 2002. In the analyzed group of patients tick bites were confirmed in 77.9%
      and the most common places of exposition were forest regions in Lower Silesia
      (Masyw Slezy, Wzgorza Twardogorskie, Kotlina Klodzka, Wzgorza Trzebnickie, Bory
      Dolnoslaskie) and in Wroclaw area. EM appeared in 55.8% cases. In cases of
      multiple ticks professionally exposured persons EM appeared only in 22.2%.

PMID- 15517810
TI  - [Occurrence of intestinal parasites among first grade students in Poland in years
      2002/2003].
AB  - In the school year 2002/2003 there were examined in Poland some of the population
      of 7-year-old children for the presence of intestinal parasites, continuing
      countrywide operation launched in 1988. METHODS: The studies were based on the
      examination of a single faecal specimen and a cellophane swab using the following
      methods: wet mount preparations in 0.9% NaCl and diluted Lugol's ioine, zinc
      sulphate centrifugal flotation and decantation. RESULTS AND CONCLUSIONS: The
      studies included 31 504 children from 15 provinces of Poland. The parasites most
      frequently encountered in the examinations included: Enterobius vermicularis (in
      3 827 of the examined, i. e. 12, 15%), Ascaris lumbricoides (in 263; 0.83%),
      Giardia intestinalis (in 217: 0.69%), Entamoeba coli (n 189; 0.60%) and Trichuris
      trichiura (in 39; 0.12%) The overall percentage of the infected children was
      15.4%. The highest number of infected children was found in the province
      warminsko-mazurskie (29.6%0), the smallest in slaskie (8.8%). The number of
      infected among children inhabiting country (19%) was significantly higher than
      among those from the towns (10.4%). The obtained results confirmed hitherto
      existing views that in Poland the epidemiological situation of infections with
      intestinal parasites is steadily improving.

PMID- 15517811
TI  - [Epidemiology of parasitic diseases in military personnel treated in the United
      Nations Interim Force hospital in Lebanon, from 1993 to 2000].
AB  - The study examined the incidence and prevalence of parasitic diseases among
      military personnel of the United Nations Interim Force in Lebanon (UNIFIL) and
      local civilian population. Additionally, the authors investigated the potential
      risk factors, including environmental conditions, influencing the incidence of
      infectious diseases. Epidemiological analysis was conducted based on the medial
      records of patients treated in the Internal and Surgical Ward of the UNIFIL
      Hospital from 1993 to 2000. The patients with parasitic diseases accounted for
      3.78% of all patients hospitalized during the analyzed period. The most frequent
      infectious diseases treated during that time were trichuriasis, ancylostomiasis,
      giardiasis and ascariasis.

PMID- 15517812
TI  - [Infectious diseases among military personnel in the catchment area of the United
      Nations Interim Force in Lebanon hospital, from 1993 to 2000].
AB  - In the study the incidence of infectious diseases among military personnel of the
      United Nations Interim Force in Lebanon and local civilian population is
      examined. Additionally, the authors investigate the potential risk factors,
      including environmental conditions, influencing the incidence of infectious
      diseases. Epidemiological analysis was conducted based on the medical records of
      patients treated in the Internal and Surgical Ward of the UNIFIL Hospital from
      1993 to 2000. The patients with infectious diseases accounted for 5.84 % of all
      patients hospitalized during the analyzed period. The most frequent infectious
      diseases treated during that time were salmonellosis and staphylococcal food
      poisoning.

PMID- 15517813
TI  - [Human metapneumovirus--new identified virus infecting human respiratory tract].
AB  - Some information regarding some characteristics of new identified virus, causing
      human respiratory diseases (named human metapneumovirus--hMPV) has been written.
      Moreover, areas of existing, frequency of infections, the possibility of
      diagnosis have been included. This virus has been isolated and identified by
      Dutch researcher, van den Hoogen, for the first time in 2001. It is suggested
      that hMPV belongs to Paramyxoviridae family, Pneumovirinae subfamily,
      Metapneumovirus genus, but it has not been confirmed by the Committee of the
      Taxonomy of Viruses, yet. This virus has been reported and demonstrated to be
      present mostly in children, but also in elderly people over 65, in Europe, North
      America, Australia and Asia, suggesting a worldwide distribution. Serological
      studies showed that all children in Netherlands had been exposed to hMPV by the
      age of 5; it means that infections with hMPV are common in the childhood. The
      presence of antibodies in retrospective serum and the presence of virus in
      numerous retrospective specimens taken from individuals with respiratory
      infections in which an etiologic agent was not initially detected indicates that
      this virus had been circulating in human beings for at least 50 years. Clinical
      diseases associated with hMPV appears to be similar to those ones associated with
      human respiratory syncytial virus (hRSV), ranging from mild upper respiratory
      tract infection to bronchiolitis and bronchopneumonia. Preliminary studies
      indicate that hMPV should be added to the list of pathogens associated with
      severe respiratory tract infections in immunocompromised patients and in chronic
      respiratory diseases patients (eg. asthma).

PMID- 15517814
TI  - [Anthrax--continuous threat to humans and animals].
AB  - Gram-positive, spore-forming, aerobic bacterium Bacillus anthracis is an
      etiological agent of anthrax a disease very dangerous to humans and all warm
      blooded animals. The spore forms are markedly resistant to unfavourable
      environmental extremes of heat, cold, desiccation, chemicals, irradiation etc.
      The vegetative forms characterised virulence factors: the antiphagocytic poly
      gamma-D-polipeptide capsule and three proteins, edema factor (EF), lethal factor
      (LF) and protective antigen (PA). Anthrax is mainly transmitted from animals to
      man through food of animal origin, animal products and contamination of the
      environment with B. anthracis and its spores. There are three types of this
      disease: cutaneous, intestinal and inhalation anthrax. Research on anthrax as a
      biological weapon began more then 80 years ago. Depending on the target chosen
      and the scale of the attack the anthrax spores may by used to contaminate of
      foodstuffs or liquids and water. The aerosolised release of anthrax spore can
      cause illness with a high fatality rate.

PMID- 15517815
TI  - [False positive and false negative reaction results based on an amplification of
      nucleic acids in infection diagnoses. Reasons and implications].
AB  - The paper discusses the most frequent causes of false positive and false negative
      results of reactions based on amplification of nucleic acids. All stages of the
      method are described beginning with sample collection up to the finishing of
      visualization of amplification product. The main aim objective of the publication
      is to draw doctors' attention to the necessity to interpret the result with
      criticism. We attempted also to demonstrate how to avoid false results.

PMID- 15517816
TI  - [Does the assay of acute phase protein concentrations in cerebrospinal fluid
      and/or in serum in patient with viral meningitis have a diagnostic value? Part
      II. Lymphocytic meningitis caused by echo 30 virus].
AB  - The aim of the study was to evaluate dynamics of selected acute phase proteins in
      serum and cerebrospinal fluid (CSF) in children with viral meningitis and to
      assess diagnostic power of protein determination for detection and treatment
      monitoring. 51 children with viral meningitis caused by ECHO 30 virus were
      included in the study group. Concentration of C-reactive protein (CRP), alpha 1
      antitrypsin (AAT), alpha1-acid glycoprotein (AAG), alpha2-haptoglobin (HPT) and
      C3 complement fragment were determined in serum and CSF at entry and at day 14
      after admittance to hospital. Control group for serum determination consisted in
      30 healthy children (Group K1) and control group for CSF determination consisted
      in 19 hospitalized children in whom the diagnosis of meningitis was not confirmed
      (group K2). The greatest rise of acute phase proteins concentration was observed
      in children in case of HPT, AAG and C3 complement when determined in serum.
      Meningitis in children that was caused by ECHO 30 virus produces slight acute
      phase reaction that is more evident in serum than in CSF. It is confirmed by
      remarkable increase of AAG, HPT, C3 complement in serum and HPT in CSF either at
      entry or at the day 14. The determination of AAG, HPT and C3 complement in serum
      have diagnostic power that is strong enough to meningitis diagnostics and
      monitoring of treatment.

PMID- 15517817
TI  - [Laboratory assessment problems of the efficacy of acellular pertussis vaccines].
AB  - Although composition of acellular pertussis vaccines is better defined than whole
      cell vaccines, differences in the formulation, content, and detoxification of
      pertussis vaccine antigens led to a unique character of each of differently
      produced acellular vaccine. Currently used methods for laboratory evaluation of
      whole-cell pertussis vaccine efficacy were found not suitable for acellular
      vaccines. There is a strong need to perform analysis and evaluation of the safety
      and efficacy profiles of acellular pertussis vaccines combined with other vaccine
      antigens (e.g. Hib) both before and after conjugation. Mechanisms of interactions
      seen after conjugation inducing weaker immunogenicity or efficacy are still
      poorly recognized.

PMID- 15517818
TI  - [Thyroid cancer in Poland in 1980-2000].
AB  - The objective of this paper was to assess the occurrence of thyroid cancer in
      Poland between 1980 and 2000 concerning incidence, hospitalisation and mortality.
      The frequency of thyroid cancer is relatively low - 0.5% in men and above 2% in
      women among all malignant. Mortality of thyroid cancer is on the low, stable
      level - 0.45 death per 100 000 in men and 1.05 in women. Hospital morbidity
      caused by thyroid cancer is almost three-fold higher then incidence. In the
      framework of 1980-2000 the substantial increase of incidence was observed
      especially since 1991 in women and in 1992-1993 and 1999-2000 in men. It could be
      associated with the pause in iodine prophylactic in 1980. Factors such radiation
      from medical treatment, ionising radiation as well as environmental, nutrition
      and genetic conditions may play role as a risk factors. In the last years
      slightly increase of incidence of thyroid cancer was observed in the population
      of 0-15. It could be possible caused by radiation after accident of the
      Chernobyl.

PMID- 15517819
TI  - [Indicators of social inequalities for school-age children health surveys].
AB  - Data from Health Behaviour in School-aged Children: A WHO Cross-national
      Collaborative Study conducted in Poland in 2002 on the representative sample of
      6383 pupils aged 11-15 yrs, were used to present different indicators of
      socioeconomic status. Traditional occupational measures are inappropriate for use
      in research on adolescents because of their limited ability to describe parents'
      occupation. Researchers involved in HBSC study developed two non-occupational
      measures that could be useful as social inequalities indicators: perceived family
      wealth (PFW) and family affluence scale (FAS). FAS scale is well correlated with
      macroeconomic measures on the national and international level. The percentage of
      families classified in the low FAS category (less than 3 points on the scale
      ranged from 0 to 7) is twice higher in Poland than in EU countries (43.1% vs.
      18.1%). FAS is easy to obtain, and more objective than PFW. Subjective family
      wealth is not recommended for subjective health outcome and quality of life
      assessment. For different health outcome and various populations the shape and
      strength of relationship between socioeconomic status and health or health
      related behaviors may change.

PMID- 15517820
TI  - [The audience of TV health programs].
AB  - The viewing figures of 36 unpaid TV health programs was assessed: the number of
      viewers, their socio-demographic status and interest in specific program. Between
      June 1998 and June 1999, non commercial TV health programs reached 0.7% to 7.6%
      TV audience, no more than 2,700.000 viewers per program. Programs broadcasted in
      evenings and winter time had more viewers. The audience consisted usually of:
      women, retired persons, rural inhabitants, persons with basic educational
      background. Pensioners were interested in every program, women in majority.
      Students, blue-collar workers and men were censorious and appreciated some
      programs only.

PMID- 15517821
TI  - Deletion 2q37.3 and autism: molecular cytogenetic mapping of the candidate region
      for autistic disorder.
AB  - Fine mapping of deletion regions in autistic patients represents a valuable
      screening tool for identifying candidate genes for autism. A number of studies
      have ascertained associations between autism and terminal 2q deletion with the
      breakpoint within 2q37. Here we describe a 12-year-old female patient with
      terminal 2q37.3 cryptic deletion and autistic behaviour. Her clinical features
      included hypotonia and feeding difficulties during infancy, coarse face with
      notably prominent forehead, prominent eyebrows, broad flat nasal bridge and round
      cheeks, small hands and feet with bilateral brachymetaphalangism, proximal
      implantation of the thumbs and short toenails, mild mental retardation and
      autistic behaviour. Recorded autistic features included early lack of eye contact
      and, during infancy, little social interactions, propensity to be stereotypically
      busy and to get anxious. In order to more closely delineate the linkage region
      for autism within 2q37, the findings in this patient were combined to those in 2
      previously reported siblings with a well documented 2q37.3 deletion, but without
      autistic disorder. The exact size of the deleted segment was determined by
      mapping the deleted region in each group with a series of specific BAC clones
      linearly ordered on the 2q37 region. The deletion in the autistic patient
      appeared to be larger [breakpoint flanked by more centromeric clones RP11-680016
      (236.9 Mb) and 201F21 (237.4 Mb)] than in the non autistic siblings [more
      telomeric clones RP11-205L13 (237.8 Mb) and 346114 (238.2 Mb)], revealing a
      distance of maximum 1.3 Mb between the breakpoints. Accordingly, the extent of
      the candidate region for susceptibility genes for autism on distal 2q is reduced
      to maximum 1.3 Mb. Comparison with another well documented autistic patient from
      the literature results in the same conclusion. These findings represent thus a
      further step towards identifying genes predisposing to autism.

PMID- 15517822
TI  - De novo complex chromosome rearrangement: a study of two patients.
AB  - Complex chromosome rearrangements (CCR) involving multiple breaks in two or more
      chromosomes are rare. We describe a girl with development delay and overgrowth
      who presents a nine-break apparently balanced de novo rearrangement involving
      chromosomes 1, 2, 3, 4 and 12, and a boy with developmental delay and seizures
      with a complex three-chromosome apparently balanced de novo rearrangement
      involving chromosomes 2, 7 and 13. The relationship between clinical
      abnormalities and apparently balanced rearrangements is discussed.

PMID- 15517823
TI  - Trisomy 22 with thyroid isthmus agenesis and absent gall bladder.
AB  - This manuscript reports a fetus of 24 weeks gestation, detected on echography to
      have congenital anomalies: intra-uterine growth retardation, facial dysmorphism,
      ventricular septal defect with aortic displacement and 8-mm nuchal skinfold
      thickness. Karyotype was performed. Post termination of pregnancy autopsy showed
      additionnal internal organ anomalies included: absent gall bladder and thyroid
      isthmus agenesis. To our knowledge, these anomalies have never been described in
      trisomic 22 fetuses. This case suggests that chromosome 22 could play a role in
      thyroid development.

PMID- 15517824
TI  - Balanced de novo translocation t(6;7)(p25;q31) and cleft palate as an isolated
      finding.
AB  - We report a prenatally diagnosed balanced de novo translocation t(6;7)(p25;q31).
      Physical examination of the baby born at term revealed only a posterior cleft
      palate. Laboratory examinations and radiologic investigations were found normal.
      Two years follow-up of the patient showed her mental and motor development was
      appropriate with her age. Our report is the first observation on balanced de novo
      translocation t(6;7)(p25;q31) and cleft palate. Association of this translocation
      and cleft palate has not been reported previously.

PMID- 15517825
TI  - Joubert syndrome co-existing with partial Xp trisomy: review of the literature.
AB  - We report a five-year-old girl who has been clinically diagnosed as Joubert
      syndrome. Her cytogenetic analysis showed 46,XX,der(2)add(2q37) karyotype.
      Cytogenetic analysis of her mother and maternal grandmother revealed a karyogram
      designated as 46,X,t (X;2)(p11.2;q37). The proband's derivative chromosome was
      further confirmed to be a translocation chromosome 2 carrying segments from
      chromosome X, which originated from a segregation event of the maternal
      grandmother's balanced translocation passed on as a balanced translocation to the
      proband's mother either. So far, a number of candidate genes including EN1 on 2q
      were analyzed for Joubert syndrome. Based on our proband's abnormal karyotype, we
      suggest that further mapping studies for the syndrome should also be directed
      towards the chromosome X segments present on the derivative chromosome 2 of our
      proband.

PMID- 15517826
TI  - Renal tubular dysgenesis with hypoplastic calvaria: report of two cases.
AB  - Renal tubular dysgenesis (RTD), a rare, lethal, autosomal recessive disorder, is
      characterized by short and poorly differentiated proximal tubules and associated
      with hypoplastic calvaria. We report two cases of RTD with hypoplasia of the
      calvaria. Microscopically, proximal tubules in the kidneys were not seen on
      routine H&E stain. Almost all tubules in the cortex were stained for epithelial
      membrane antigen (EMA), confirming the absence of proximal tubule
      differentiation. The autopsy findings, microscopic features and the etiology of
      this rare condition is discussed and compared with literature data.

PMID- 15517827
TI  - De novo paracentric inversion 14q13q24.1 in a patient with severe involuntary
      movements, epilepsy, oligodontia and dysmorphic features.
AB  - We describe a 22-year-old woman with a de novo paracentric inversion of the long
      arm of chromosome 14 with breakpoints at q13 and q24 and associated with
      epilepsy, dysarthria and severe incapacitating involuntary movements present
      since birth. These movements were incessant when awake but absent when asleep.
      She had unusual facies with downward slant of palpebral fissures, epicanthi,
      broad philtral groove, flat malar region, large, cup shaped and low-set ears, and
      short neck. Her decidual and permanent dentition lacked all premolars and molars.
      Psychological assessment at ages 6 and 15 years showed mild mental retardation.
      In spite of the aggravation of the neurological symptoms no decline of mental
      capacity was observed. A brain MRI was normal at 19 years of age. Early on EEG
      showed changes compatible with partial epilepsy, and at later stages there was,
      contrary to expectation, only a mild background slowing. Urinary metabolic
      screening tests and a search for vacuolated lymphocytes were negative.
      Previously, four cases with a similar inversion have been described. Of these,
      three were familial with normal phenotype, and the fourth was de novo with severe
      mental retardation, microcephaly and involuntary movements. Our case is the
      second de novo inversion of the long arm of chromosome 14 with breakpoints at q13
      and q24. The observations in the two patients suggest that this chromosomal
      rearrangement is associated with a congenital complex movement disorder.

PMID- 15517828
TI  - Communicative competence and behavioural phenotype in children with Smith-Magenis
      syndrome.
AB  - Smith-Magenis syndrome is characterized by a range of minor physical and facial
      abnormalities and is caused by a de novo deletion on chromosome 17. Most children
      function in the moderate to severe ranges of mental retardation. Results of a
      survey on adaptive skills, communicative competence and behavioural abnormalities
      in 20 children are reported. The findings suggest a strong desire to get in
      social contact and maintain conversations in spite of their limited cognitive
      processing. As a group, children with SMS are presenting with severe behavioural
      abnormalities, e.g. self-injury, extreme irritability, ritualistic behaviour.
      Behaviour problems are more severe than in other genetic syndrome groups as a
      comparison with Prader-Willi- and Fragile-X-syndrome children reveals. However,
      functional analysis suggests that it is not independent from situational
      variables. There is a strong need for behavioural intervention planning as part
      of family services.

PMID- 15517829
TI  - Toxic hepatitis in a case of Angelman syndrome associated with Lennox-Gastaut
      syndrome.
AB  - We report a 26-month-old boy with Angelman syndrome associated with Lennox
      Gastaut syndrome, who developed a rash and a persistent toxic hepatitis after
      lamotrigine was added to valproate therapy. The patient had typical findings of
      both Angelman and Lennox-Gastaut syndromes. Chromosome analysis performing by
      FISH analysis showed a deletion in chromosome 15 (q11.2 q11.2). Although some
      cases of Angelman syndrome associated with Lennox-Gastaut syndrome were reported
      in the literature, valproate and/or lamotrigine induced toxic hepatitis in
      Angelman syndrome has hitherto never been described. We conclude that VPA and LTG
      combination should be given with great caution or avoided in patients with
      Angelman syndrome.

PMID- 15517830
TI  - A case with spondylo-metaphyseal dysplasia type A4.
AB  - We present a case with spondylo-metaphyseal dysplasia type A4 characterized by
      ovoid vertebral bodies with anterior tongue-like deformities, widened irregular
      and sclerotic metaphyseal changes, short iliac wings, slightly short long bones
      and short tubular bones of the hands with irregular metaphyses. She also had
      bipartite trochlea and irregular patellar margins, which have not been described
      in spondylo-metaphyseal dysplasia types to date.

PMID- 15517831
TI  - Diaphragmatic hernia with extralobar lung sequestration in the Beckwith-Wiedemann
      syndrome.

PMID- 15517832
TI  - Acanthosis nigricans in a boy with achondroplasia due to the classical Gly380Arg
      mutation in FGFR3.

PMID- 15517833
TI  - Attention-deficit/hyperactivity disorder, speech delay and polymicrogyria
      associated with trisomy 18 mosaicism.

PMID- 15517834
TI  - Laryngomalacia, choanal atresia and renal anomaly in a newborn with Freeman
      Sheldon syndrome phenotype.

PMID- 15517835
TI  - Sliding hiatal hernia associated with Apert syndrome: a first case report.

PMID- 15517836
TI  - Trisomy 11/22 diagnosed by spectral karyotyping (SKY).

PMID- 15517837
TI  - Diagnosis of hearing impairment: factors of delay.
AB  - In a retrospective study based on parents' personal interviews, the diagnosis
      circumstances were analysed in a group of 88 deaf children (moderate to profound
      deafness). We reported first the age when the parents emitted doubts, and second
      the age of diagnosis. It appeared that the age of first suspicions, and of
      diagnosis, was correlated to the degree of deafness. The population of children
      was divided in two groups depending on the presence of a delay or not in the
      diagnosis. The first group (24 children) was diagnosed early because of neonatal
      screening, or of early suspicions by parents or pediatrician. In the second group
      (64 children) were a delay was observed, seven causes were identified with
      variable frequency according to the level of deafness. The first four main causes
      for delayed diagnosis were: 1) parents, 2) medical refutation, 3) otitis media
      with effusion (OME), 4) progressive hearing loss. In conclusion, the age of
      diagnosis and the age of first suspicions were too late. Universal neonatal
      screening is recommended but do not appear to be the exclusive procedure to
      reduce the diagnostic's delay. This analysis of the factors of delay, prompted us
      to recommend: 1) information to parents on deafness, 2) careful attention to
      parents suspicions, 3) an objective evaluation of auditory function,especially
      after OME cure and 4) a follow-up of children to identify progressive hearing
      loss.

PMID- 15517838
TI  - Varicella zoster virus: beyond facial paralysis.
AB  - J. Ramsay Hunt's hypothesis that herpes zoster oticus results from a reactivation
      of the herpes zoster virus in the geniculate ganglion, has been supported by the
      demonstration of varicella zoster viral DNA in the geniculate ganglion of the
      side with facial paralysis in patients with Ramsay Hunt syndrome, with the use of
      the polymerase chain reaction. Similarly, DNA of the varicella zoster virus has
      been identified in the spiral and vestibular ganglion as well. We report on three
      patients with cochleovestibular symptoms as the first manifestations of Ramsay
      Hunt syndrome. A 64-year old woman and a 72-year old man presented with vertigo
      and an auricular herpetiform eruption. Only the woman developed later on a mild
      facial paralysis. A 58-year old man presented with an acute cochleovestibular
      syndrome, serologically proven to be a varicella zoster viral reactivation, which
      was followed three weeks later by the typical cutaneous recrudescence. We believe
      that these cases result from reactivation of latent varicella zoster virus in the
      spiral and/or vestibular ganglion. As the varicella zoster virus is dormant in
      the non-neuronal satellite cells, the facial symptoms in our patients as well as
      the high incidence of cochleovestibular symptoms in classical Ramsay Hunt
      syndrome can be explained by viral transmission across the nerves inside the
      internal auditory canal. Therefore, we think there are grounds to recommend a
      prompt treatment with an antiviral and a corticosteroid agent, not only in case
      of an acute facial paralysis but also when confronted with an acute
      cochleovestibular syndrome.

PMID- 15517839
TI  - The effect of ventilation tubes on otoacoustic emissions. A study of 106 ears in
      62 children.
AB  - The aim of this investigation was to study the presence and the characteristics
      of transient evoked otoacoustic emissions (TEOAE) in ears with ventilation tubes.
      Theoretically the small mass and the opening of the tube could influence the OAE.
      We studied a population of children between the age of 3 and 9 years with
      functional ventilation tubes and a normal hearing on pure tone audiometry
      (Fletcher index < 25 dB). A total of 110 ears from 62 children were included.
      According to the criterion of 70% wave reproducibility, TEOAE were present in
      86.7% of the ears. Looking at the reproducibility in the different frequency
      bands of the response, it was found that the TEOAE were strongest in the 2 kHz
      frequency band. It is concluded that the measurement of TEOAE can be used as a
      useful hearing test in young children with ventilation tubes, maybe even when
      pure tone audiometry is not yet possible. However, false negative results were
      found in about one tenth of the ears.

PMID- 15517840
TI  - Chondrosarcoma of the epiglottis: report of a case treated with CO2 laser
      epiglottectomy.
AB  - Chondrosarcoma of the larynx is a rare slow-growing malignant tumour with
      approximately 240 cases reported in the literature: the cricoid cartilage is the
      most commonly affected site (72-75%), in rare case was described of epiglottis (1
      2%). We report a case of a chondrosarcoma of the epiglottis treated with CO2
      laser epiglottectomy. The patient was referred with dysphonia, dysphagia and
      halitosis that started four months before. Indirect laryngoscopy revealed a large
      smooth mass with a roundish appearance and a pearly-grey colour, as big as a nut,
      apparently arising from the laryngeal surface of the epiglottis, causing
      obliteration of the piriform fossa. The definitive histopathological report
      showed microscopically, the tumour was low-grade (grade I) chondrosarcoma. A
      literature review regarding chondrosarcomas of the epiglottis is presented. The
      diagnosis, histology and treatment of these tumours are discussed. In particular
      we examine the controversy of conservative surgery vs. total laryngectomy. A
      conservative surgical approach is typically appropriate in light of this tumour's
      low-aggressive nature.

PMID- 15517842
TI  - Mii Amo Spa, Sedona, Arizona.

PMID- 15517843
TI  - Revisiting the Mii Amo Spa, Sedona, Arizona.

PMID- 15517841
TI  - Recurrence rates in endonasal surgery for polyposis.
AB  - OBJECTIVE: To assess the prognostic factors of recurrence in a cohort of patients
      operated on for polyposis by means of endonasal endoscopic surgery. METHODS:
      Prospective study of 227 patients operated on for polyposis in a single
      institution between 1993 and 2001. The mean follow-up period was 24 months (range
      12 months to 60 months). Nine parameters were analysed to study their association
      with polyp recurrence: age, gender, smoking history, presence of asthma, allergy,
      non-steroidal anti-inflammatory drugs (NSAID) intolerance, recurrent sinusitis,
      previous nasal surgery, and polyp extension. Analysis of recurrences was
      accomplished using the Kaplan-Meier survival curves and differences were analysed
      using the log-rank test. The Cox proportional hazards model was used to estimate
      the effect of individual risk factors on polyp recurrence. A probability value of
      p < 0.05 was the level of significance selected. RESULTS: During the study
      period, recurrences developed in 55 patients, giving a rate of 24%. In the
      univariate analysis, NSAID intolerance, asthma, revision surgery and polyp
      extension were associated with recidivism. The other mentioned factors did not
      attain statistical significance. However, the multivariate analysis demonstrated
      that only NSAID intolerance and asthma are independent predictive factors for
      recurrence. CONCLUSIONS: Patients presenting NSAID intolerance or asthma are at
      risk for the development of recurrences after endonasal surgery for nasal
      polyposis.

PMID- 15517844
TI  - A double-blind combination study of clonazepam with sertraline in obsessive
      compulsive disorder.
AB  - This double blind, randomized, parallel, placebo-controlled study investigates
      whether clonazepam accelerates and/ or increases the overall response in patients
      with obsessive compulsive disorder (OCD) who are treated with sertraline. Thirty
      seven patients were randomized with 20 in the sertraline and clonazepam group and
      17 in the sertraline and placebo groups. Male and female outpatients, age 18-65
      years, met criteria for a primary diagnosis of obsessive compulsive disorder
      according to DSM-IV, as determined by the structured clinical MINI interview.
      Appropriate safety and efficacy parameters were measured throughout the study.
      The determination of efficacy was based primarily on changes from baseline to the
      last observation taken through week 12. Analysis revealed no significant
      difference between groups at endpoint on the main scale.

PMID- 15517845
TI  - Modafinil as adjunctive therapy in depressed outpatients.
AB  - The wake-promoting agent modafinil (PROVIGIL) may prove useful as an adjunctive
      treatment in patients with suboptimal responses to antidepressant regimens. This
      retrospective chart review describes the use of modafinil as an adjunct to
      antidepressant therapy in 78 outpatients in a general psychiatric practice and
      discusses in detail treatment outcomes for 3 patients. Statistically significant
      improvements in mean Carroll Depression Rating Scale scores (p < 0.01), Visual
      Analog Scale scores for overall feeling (p < 0.003), and Clinical Global
      Impression of Severity ratings (p < 0.001) were demonstrated following treatment
      with modafinil. Treatment with modafinil rapidly improved wakefulness, fatigue,
      and everyday functioning in individual cases. Modafinil was well tolerated in
      combination with antidepressants and other medications. These findings suggest
      that adjunctive modafinil may improve treatment outcomes when used with
      antidepressant therapy in depressed patients, particularly in those with
      problematic sleepiness or fatigue.

PMID- 15517846
TI  - State personality disorder in social phobia.
AB  - To examine the effects of state on personality disorder characteristics, we
      compared individuals with social phobia before and after psychological
      intervention. Administration of the Personality Disorder Questionnaire (PDQ-4)
      before and after treatment allowed for the identification of three groups of
      patients: (1) individuals who showed elevated PDQ-4 scores but little changes
      from intake to post treatment (Trait PD group; n = 28); (2) individuals who
      showed a decrease in PDQ-4 scores from intake to post treatment (State group; n =
      33); and (3) a group with no significant personality disorder characteristics at
      pre or post-treatment (No PD group; n = 32). There were trend differences between
      the Trait, State and No PD groups for being single, never married (81.5%, 44.4%,
      and 56.3%, p < .05) and a significant difference for having the generalized form
      of Social Phobia (96.4%, 88.9%, and 59.4%, p < .0001). The groups also differed
      in their level of trait anxiety (61.6, 51.2, 44.5, p < .001). Groups also
      differed in level of the personality measure Harm Avoidance (26.3, 23.3, 19.8, p
      < .0002). The reduction of personality disorder traits in the State PD groups
      from intake to post-treatment was not specific to any particular personality
      disorder or personality disorder cluster. Trait personality appeared to have a
      higher risk for suicide compared to the other two groups. A State Personality
      group was identified in individuals with social phobia by following changes in
      personality pathology from before and after a psychological intervention.

PMID- 15517848
TI  - Aripiprazole: review of its pharmacology and therapeutic use in psychiatric
      disorders.
AB  - The discovery of antipsychotic medications has revolutionized the treatment of
      schizophrenia and other psychotic disorders. However, side effects such as
      extrapyramidal symptoms (EPS) and tardive dyskinesia (TD), electrocardiogram
      (ECG) changes, weight gain, and metabolic disturbances indicate the continued
      need to develop new agents. The introduction of atypical drugs such as clozapine,
      risperidone, olanzapine, quetiapine, and ziprasidone has widened our choices.
      This article provides an overview of the pharmacology, efficacy, and techniques
      for the clinical use of aripiprazole, a novel agent with a unique pharmacological
      profile.

PMID- 15517847
TI  - The utility of intramuscular ziprasidone in the management of acute psychotic
      agitation.
AB  - Many psychiatric illnesses, including chronic schizophrenia, bipolar disorder,
      and dementia, are characterized by episodes of acute agitation, making
      administration of oral agents difficult or impossible. Ziprasidone, the first
      atypical antipsychotic available in both intramuscular (IM) and oral
      formulations, has demonstrated significant control of acute agitation within 15
      minutes, as seen in two 24-hour studies in patients with schizophrenia.
      Improvement was maintained for > or = 4 hours, and a low incidence of
      extrapyramidal symptoms, akathisia, and dystonia as well as no excessive sedation
      were observed Also, two 7-day studies (n = 132 and n = 306) and one 6-week study
      (n = 567) of sequential IM/oral ziprasidone versus IM/oral haloperidol in
      patients with psychotic disorders found IM ziprasidone more effective than IM
      haloperidol within 3 days of IM treatment; both drugs produced further comparable
      improvements in efficacy parameters after transition to oral therapy. IM
      ziprasidone was associated with a lower incidence of movement disorders than was
      haloperidol in all of these studies. Overall, discontinuations were similar for
      IM ziprasidone and haloperidol in the comparative trials, including the
      sequential IM/oral studies. However, in the 6-week sequential IM/oral trial, the
      rate of discontinuation due to adverse events was twice as high among haloperidol
      vs ziprasidone patients. This report focuses on the pharmacology, clinical
      efficacy, and tolerability of IM ziprasidone, and provides an overview of the
      utility of other commonly used antipsychotics in the management of acute
      psychotic agitation.

PMID- 15517850
TI  - Psychosis induced by smoking cessation clinic administered anticholinergic
      overload.
AB  - Anticholinergic agents have multiple CNS effects, even when used in therapeutic
      doses. These can include sedation, amnesia, delirium and, in rare cases,
      psychosis. While there is some symptom overlap between delirium and psychosis,
      psychotic patients will have a clear sensorium. We present the case of a 59-year
      old male who became psychotic and required hospitalization after the
      administration of a large anticholinergic load from a smoking cessation clinic.
      We will review the literature regarding previous cases of anticholinergic
      medication induced psychosis, discuss treatment options and review the clinical
      effects of anticholinergic medications.

PMID- 15517849
TI  - An association of Ephedra use with psychosis and autonomic hyperactivity.
AB  - Ephedra extract is used in a number of dietary supplements taken for a variety of
      purposes including weight loss. Although recent events have led to calls for
      Ephedra to be removed from the market and the FDA has had over 18,000 adverse
      event reports, newspaper reports cite only a few instances of clearly associated
      adverse events associated with Ephedra use. In this communication, we review the
      literature and present a case report of Ephedra use associated with the onset of
      psychosis and autonomic hyperactivity after administration of risperidone. We
      conclude that the behavioral effects of Ephedra are a public health concern.

PMID- 15517851
TI  - Minimally invasive orthopaedic trauma surgery: a review of the latest techniques.
AB  - Computer assisted fluoroscopic surgery is at the forefront of the ability to
      continue and pursue minimally invasive surgical options in orthopaedic surgery.
      Many systems afford the surgeon three-dimensional views and biplanar imaging for
      placement of orthopaedic implants in difficult areas. The current literature
      regarding these techniques is limited. The indications are poorly defined. The
      common thread of all techniques, however, is the preservation of the soft tissue
      attachments and the biology of the fracture hematoma. Currently we are using
      first generation implants. It appears that malalignment is the biggest problem
      with any of these techniques and long-term prospective studies will be required
      to evaluate whether or not these theoretical advantages become clinically viable
      and functional for patient care.

PMID- 15517852
TI  - Osteobiologics.
AB  - "Osteobiologics" is the term that has been introduced to refer to the class of
      engineered materials that have been created and which promote healing of
      fractures and bone defects. The list of osteobiologics is rapidly expanding as
      new products incorporating osteoconductive materials are mixed with a variety of
      osteoinductive proteins, demineralized bone, and preparations of osteogenic
      cells. The growth in osteobiologics has been stimulated by the early success of
      osteoconductive materials as graft substitutes in the repair of fractures and by
      the increasing demand for grafts in all areas of orthopaedics. Although
      allografts have historically been employed with success, the number of donors has
      grown much slower than demand leading to the development of artificial materials.
      Manufactured bone graft substitutes, or osteobiologics, attempt to mimic the
      components of an autogeneous bone graft by reproducing the bone matrix, which is
      osteoconductive and osteoinductive. Other products aim to introduce osteogenic
      cells by concentrating bone marrow while others introduce differing growth
      factors from platelets in peripheral blood. Very few of these products have been
      supported by appropriate clinical studies and as such their value is unknown.
      Orthopaedic surgeons employing these products must understand the basic science
      principles behind their development in order to understand the indications and
      limitations of their application. Properly designed clinical studies should be
      performed to determine the usefulness and cost-effectiveness of both current and
      future products.

PMID- 15517853
TI  - A minimally invasive approach for plate fixation of the proximal humerus.
AB  - Plate fixation for unstable fractures of the proximal humerus has seen mixed
      results as evidenced by the trials of new methods of fixation. The deltopectoral
      surgical approach is most frequently used and requires significant muscle
      retraction and soft tissue stripping to expose the lateral humeral neck. This may
      contribute to avascular necrosis and fixation failure. Lateral approaches have
      been limited to 5 cm distal to the acromion because of the course of the anterior
      branch of the axillary nerve. A recent anatomic study has demonstrated the
      predictability of the position of the axillary nerve as it crosses the anterior
      deltoid raphe, which allows it to be isolated and protected, and dissection can
      be extended distally. In addition, no accessory motor branches to the anterior
      head of the deltoid cross the raphe, so extending an incision through the raphe
      after protecting the main motor branch of the axillary does not place the
      innervation to the anterior deltoid at risk. This surgical approach allows
      exposure of the proximal humerus and indirect reduction of the fracture, with
      subsequent locking plate fixation, adhering to the principles of biological
      fixation.

PMID- 15517854
TI  - Proximal humerus fractures in the elderly are we operating on too many?
AB  - Proximal humerus fractures in the elderly are a relatively rare injury, the
      treatment of which remains controversial, especially regarding Neer displaced two
      part, and three-part and four-part fractures. Operative indications for most
      displaced proximal humerus fractures in the elderly remain poorly defined, but
      recent literature is actually supporting less aggressive approaches except for
      the most severe fractures. Recent epidemiological and larger scale retrospective
      studies fail to show a significant functional difference between operative and
      non-operative treatment of displaced two-part and three-part fractures in the
      elderly. Most four-part fractures appear to be best treated with
      hemiarthroplasty. Recent meta-analyses show a need for well-executed, randomized,
      prospective studies that can be used to provide evidence-based templates for
      appropriate management of displaced proximal humerus fractures in the elderly.

PMID- 15517855
TI  - Elbow fracture-dislocations: the role of hinged external fixation.
AB  - Fracture-dislocations of the elbow remain a complex problem in orthopaedics. The
      myriad of treatment protocols and methodologies focuses on precise articular
      alignment and restoration of the skeletal architecture. The goal is to re
      establish function as quickly as possible so as to allow rehabilitation involving
      the full range of motion. Surgical management, primarily reconstruction of the
      secondary stabilizers of the elbow joint as well as preserving soft tissue
      structures, subsequently provides the possibility of a speedier recovery. If
      proper skeletal alignment does not confer enough stability, hinged external
      fixation becomes an integral part of the treatment strategy for the
      reconstructive and trauma surgeon.

PMID- 15517856
TI  - A meta-analysis of the literature on distal radius fractures: review of 615
      articles.
AB  - A structured meta-analysis of the available literature was performed to evaluate
      the outcome of the treatment of displaced intra-articular fractures of the distal
      radius. A comprehensive search of Medline using the key words "radius" and
      "fracture" revealed over 4,000 articles. After limiting the search to clinical
      trials in English and excluding pediatric and geriatric age groups as well as
      biomechanical and animal studies, 615 abstracts were identified in the period
      from 1976 to May 1998. Thirty-one articles met the inclusion and exclusion
      criteria. These included two prospective randomized comparative trials, two non
      randomized comparative trials, one half prospective case series and half
      historical control, and 27 papers on case series. Four papers dealt with external
      fixation versus closed reduction and cast treatment and one paper looked at open
      reduction internal fixation with or without additional external fixation. There
      was insufficient data to perform a scientific meta-analysis because of the poor
      quality of the studies and lack of a uniform method of outcome assessment.
      However, the data from the comparative trials showed that external fixation was
      favored over closed reduction and casting. Additionally, comparing the results of
      the case series showed that external fixation was superior to internal fixation.

PMID- 15517857
TI  - Management of acetabular fractures in the elderly.

PMID- 15517858
TI  - Acetabular fractures in the elderly.

PMID- 15517859
TI  - Early versus delayed fixation of isolated closed femur fractures in an urban
      trauma center.
AB  - The use of intramedullary rods is accepted as the gold standard for treatment of
      closed femur fractures. Early fixation of these fractures has been shown to be
      beneficial in the multiply-injured patient. This retrospective review was
      undertaken to examine the isolated femur fractures in an urban trauma center over
      a six-year period. Of the 76 patients included in the study, 42 underwent early
      fixation (less than 48 hours after injury) and 34 had delayed fixation (more than
      48 hours after injury). There was no statistical difference in postoperative
      complications between the two groups. Fixation performed within 48 hours did not
      seem to decrease morbidity when compared to fixation performed after 48 hours.
      Length of stay and hospital costs were increased with delayed fixation.

PMID- 15517861
TI  - Possible errors in pin insertion positions using the C-arm.
AB  - In order to measure errors in pin positions, a tibia with referenced pin
      insertions was radiographed in various locations using a mini C-arm. Changes in
      pin position locations up to seven millimeters and twelve degrees were found. To
      minimize these errors, limbs should be centered and parallel to the plane of the
      imaging screen of the C-arm. If possible, pin insertions should be made in this
      plane. Magnification due to the distance from the screen should be determined for
      precise pin positioning.

PMID- 15517860
TI  - Staged management of high-energy proximal tibia fractures.
AB  - High-energy proximal tibia fractures are complicated by soft tissue compromise
      and this may result in sub-optimal outcomes. There is a high association of open
      injuries, compartment syndromes, and vascular injuries with these bony
      disruptions. Surgical treatment of these injuries has been associated with
      significant complications such as infection, knee stiffness, malunion, loss of
      fixation, soft tissue failure, and amputations. The loss of fixation is an issue
      especially in the elderly, with failure associated with age more than sixty
      years, premature weight bearing, preoperative displacement, fracture
      fragmentation, and severe osteoporosis. The use of two-stage reconstruction for
      the treatment of distal tibia fractures has been successful in decreasing the
      complication rates, including wound compromise. The two stages involve: 1.
      stabilization of the injured limb with a bridging external fixator to allow the
      soft tissues to improve and recover and 2. definitive fixation for reconstruction
      of the articular surface and meta-diaphyseal fractures. The use of such a
      protocol has been proposed for high-energy proximal tibia fractures to decrease
      the high rate of soft tissue compromise associated with traditional open methods
      of treatment. The choice of definitive fixation may include plates, nails, or non
      bridging external fixation.

PMID- 15517862
TI  - Interaction between the pura and E2F-1 transcription factors.
AB  - BACKGROUND: Cell proliferation is regulated by E2F-1 which facilitates expression
      of genes involved in entry into S-phase. Release of E2F-1 from binding partners,
      e.g. pRb, is critical for G1/S progression. However ectopic E2F-1 overexpression
      activates p53 and inhibits growth. Previously, the multifunctional Pura protein
      was found to bind to E2F-1 and inhibit E2F-1 transcriptional activity. MATERIALS
      AND METHODS: Pura deletion mutants were assayed for: in vitro binding to E2F-1,
      inhibition of E2F-1-induced promoter activation and effects on cell
      proliferation. Two RNA species with specific binding to E2F-1 and Pura were
      analyzed for their effects on E2F-1/Pura binding and cell growth. RESULTS: The N
      terminal 72 amino acids of Pura were involved in E2F-1 binding, inhibition of
      promoter activation by E2F-1 and reversal of E2F-mediated growth inhibition. The
      RNA species disrupted Pura/E2F-1 interaction and affected cell growth.
      CONCLUSION: E2F-1/Pura interaction has a role in the control of cell
      proliferation.

PMID- 15517863
TI  - Loss of heterozygosity and nonsense mutation in Apc in azoxymethane-induced
      colonic tumours in min mice.
AB  - C57BL/6J Min/+ mice, which carry a nonsense mutation in Apc, were injected twice
      neonatally with 5 mg azoxymethane (AOM) /kg body weight. AOM treatment in
      comparison with untreated Min mice increased the incidence and number of colonic
      tumours from 6/14 to 22/24 (incidence) and 0.64+/-0.9 to 4.0+/-3.5 tumours per
      mice, respectively. Colonic tumours were analysed for loss of heterozygosity
      (LOH) in Apc, and 32 of the samples showed LOH whereas 14 did not. In untreated
      Min mice, all 8 tumours had LOH in Apc. All tumour samples from the AOM-treated
      Min mice were analysed for nonsense mutations between codons 686 and 1217 in the
      Apc gene, and one sample had a G-->A transition mutation in codon 1047. No beta
      catenin mutations in the region coding for phosphorylation sites important for
      degradation were found. In conclusion, the main mechanism for colonic tumour
      induction in AOM-induced Min mice is LOH in Apc, but Apc nonsense mutations may
      also occur.

PMID- 15517864
TI  - Acute changes in U937 nuclear Ca2+ preceding type 1 "apoptotic" programmed cell
      death due to MK 886.
AB  - BACKGROUND: MK 886, a 5-lipoxygenase inhibitor, induces a type 1 "apoptotic" form
      of programmed cell death in Bcl-2-positive U937 monoblastoid cells. In Ca2+
      depleted, nonpermeabilized U937 cells studied with MK 886 in a Ca2+-free medium,
      an acute increase in Ca2+ occured within 10 to 20 seconds, detected with fura-2
      measured with a spectrofluorimeter. METHODS AND RESULTS: The increased
      fluorescence was nuclear in location, as judged by confocal microscopy. The
      antioxidant, N-acetyl-L-cysteine, three agents that inhibit mitochondrialfunction
      at identified sites, antimycin A, atractyloside and cyclosporin A, the L/N
      channel inhibitor, loperamide and BAPTA, an intracellular Ca+ chelator preloaded
      into cells each reduced the extent or prevented the acute MK 886-induced rise in
      Ca2+, as determined by radiometric detection. Rhodamine-2, a more selective
      mitochondrial Ca2+ probe, provided no evidence for nuclear Ca2+ originating from
      that extra-nuclear site or from the endoplasmic reticulum. With 2', 7'-dichloro
      dihydrofluorescein-labelled cells to detect reactive oxygen species, MK 886
      increased the initial fluorescent signal from a number of intracellular, largely
      extra-nuclear sites, including mitochondria. Two chemicals that inhibit the
      function of Bcl-2, HA14-1 and 2-methyl-antimycin A3, reduced the Ca2+ response to
      MK 886, if pre-incubated with the Bcl-2-positive U937 cells at 37 degrees C for
      several hours. MK 886 was previously shown to induce reactive oxygen species and
      a fall in mitochondrial membrane potential in both Bcl-2-positive U937 and in Bcl
      2-negative PC-3 prostate and panc-1 pancreatic cancer cells. The latter solid
      tumor cells undergo an atypical "type 2" PCD without an acute rise in nuclear
      Ca2+. CONCLUSION: These results are consistent with an MK 886-induced increase of
      reactive oxygen species from intra-cellular sites including mitochondria which
      release Ca2+ located primarily at or near nuclei. These events may involve Bcl-2
      participating in some form of Ca2+ channel and nuclear Ca2+ binding proteins
      undergoing conformational changes due to reactive oxygen species. Reasons for the
      different PCD responses in Bcl-2 positive lympho-hematopoietic compared to Bcl-2
      negative solid cancer cell lines, respectively with and without the induced
      nuclear Ca2+ signal, remain to be defined.

PMID- 15517865
TI  - An effective in vitro antitumor response against human pancreatic carcinoma with
      paclitaxel and daunorubicin by induction of both necrosis and apoptosis.
AB  - The highly metastatic human pancreatic cell line L3.6 was used to study
      mechanisms for antitumor activity with various chemotherapeutic drug
      combinations. The most effective drugs were daunorubicin (IC50 0.4 microM),
      doxorubicin (IC50 22 microM), paclitaxel (IC50 5.3 microM) and 5-fluorouracil
      (IC50 5.4 microM). The most effective drug combination was equitoxic
      concentrations of paclitaxel and daunorubicin. Kinetic analysis demonstrated that
      both paclitaxel and daunorubicin had to be added simultaneously for maximum
      cytotoxicity. Daunorubicin treatment alone demonstrated ROS (reactive oxygen
      species) induction and cellular morphological changes more consistent with
      chemical damage in a total of 93% of the cells and apoptotic changes in 20% of
      the cell population. The apoptosis induced by daunorubicin does not appear to be
      caspase-dependent, as demonstrated by the lack of conversion of the procaspases 8
      and 3. Within 24 h of treatment with paclitaxel, Bcl-2 formed a doublet at 26
      kilodaltons and the expression was abrogated with daunorubicin and the
      combination of the two drugs as determined by Western blots. These data suggest
      that the human pancreatic cell line L3.6 is more effectively killed following
      treatment with chemotherapeutic agents that cause death through at least two
      pathways, a caspase-dependent and caspase-independent apoptosis and necrosis.

PMID- 15517866
TI  - Effect of confluence state and passaging on global cancer gene expression pattern
      in oral carcinoma cell lines.
AB  - BACKGROUND: After establishment of a cell culture, inhomogenous growth and cell
      selection takes place at early passages. Reproducing the same confluence state
      among experiments might be difficult. MATERIALS AND METHODS: Here we used cDNA
      arrays to compare the global gene expression pattern of two oral cancer cell
      lines at 80%, 100% and super-confluence stages. Also, the stability of the global
      gene expression pattern during culture was assessed in two cell lines at passages
      10 and 53 (early and late passage). An intraclass correlation coefficient test
      was used for comparisons. RESULTS: The consistency between the different
      confluence states was almost perfect (> 0.8) and substantial (0.6-0.8). Also the
      consistency between early and late passages was almost perfect in the cell lines
      used. CONCLUSION: Our results indicate that neither the state of confluence nor
      passage have significant effects on the global gene expression profile, despite
      the variability in expression levels of individual genes.

PMID- 15517867
TI  - Treatment with IL-2 and IL-12 inhibits tumour cell division in SL2 lymphoma.
AB  - We examined which mechanism plays a dominant role in the rejection of solid SL2
      lymphoma treated with locally applied IL-2 and/or IL-12. This treatment resulted
      in about 80% cures. There was a moderate influx of leukocytes in the tissue
      surrounding tumours; yet these cells failed to invade the solid tumours.
      Potentially cytotoxic cells were not observed in close proximity to areas of
      tumour cell death, indicating that cell-mediated cytotoxicity is not an important
      mechanism of tumour rejection in this model. Similarly, inhibition of blood
      vessel growth and/or blood vessel injury could be ruled out as mechanisms, since
      tumour rejection was not accompanied by decreased angiogenesis or blood vessel
      injury. We did observe that many tumour cells die via apoptosis or necrosis and
      that tumour cell division in cytokine-treated mice is inhibited. In conclusion,
      IL-2/IL-12-mediated tumour rejection in solid SL2 lymphoma is mainly due to a
      shifted balance between tumour cell death and tumour growth caused by inhibition
      of proliferation, rather than to direct cell cytotoxicity or destruction of blood
      vessels.

PMID- 15517868
TI  - PAkt, cyclin D1 and p27/Kip.1 in glioblastomas with and without EGFR
      amplification and PTEN mutation.
AB  - BACKGROUND: PIP3, generated by P13-K activates Akt which inactivates AFX/FKHR;
      with the consequent decrease in p27/Kip.1 expression and enhancement of cyclin D1
      expression through FRAP/mTOR. PTEN lipid phosphatase degrades PIP3 and negatively
      regulates Akt, whereas this is activated by EGFR through PI3. In glioblastomas,
      PTEN is mutated in 27%-40% and EGFR amplified in 60%-65% of cases. MATERIALS AND
      METHODS: PTEN mutation and EGFR amplification by PCRP Akt, p27/Kip.1 and cyclin
      D1 by immunohistochemistry, apoptosis by TUNEL and MIB.1 LI were studied in a
      series of 65 operated glioblastomas. RESULTS: EGFR amplification and PTEN
      mutation were present in 50% and 30% of glioblastomas, respectively. No
      relationship between EGFR amplification and PTEN mutation, and p27/Kip. 1 and
      cyclin D1 was found. However, cyclin D1 was positive in 69% of Akt-expressing
      areas, whereas p27 was positive in 30% only. CONCLUSION: A direct relationship is
      more evident between cyclin D1 and p27/Kip.1 and Akt than with PTEN and EGFR.

PMID- 15517869
TI  - Apoptosis in cervical cancer cells: implications for adjunct anti-estrogen
      therapy for cervical cancer.
AB  - BACKGROUND: Many tumors show dependence on estrogen for growth and establishment
      of drug resistance. We examined the effects of estrogen on cervical cancer cells
      exposed to apoptotic agents including drugs used for treatment. MATERIALS AND
      METHODS: We tested the effect of estradiol on apoptosis in three cervical cancer
      cell lines. Apoptosis was measured by endonucleolytic degradation of DNA. Bcl-2
      was measured by Western analysis. RESULTS: Estradiol reduced the percentage of
      cells undergoing apoptosis after exposure to the DNA-damaging agents UVB,
      mitomycin-C and cisplatin. Protection against taxol-induced apoptosis was
      marginal. Protection was independent of HPV gene expression, and not specific to
      apoptosis induced by DNA damage, since estradiol significantly reduced the number
      of apoptotic cells produced after exposure to indole-3-carbinol (I3C), a non
      genotoxic phytochemical effective in preventing HPV-induced tumors. Higher
      concentrations of I3C overcame the anti-apoptotic effect of estradiol. Treatment
      with I3C resulted in loss of the survival protein Bcl-2, and estradiol partially
      reversed this effect. CONCLUSION: Estrogen protects cervical cancer cells treated
      with DNA-damaging agents; UVB, mitomycin-C and cisplatin, from apoptotic death.
      For I3C, which induces apoptosis and is anti-estrogenic, the amount of apoptosis
      versus survival and the level of Bcl-2 depend on the I3C/estradiol ratio.

PMID- 15517870
TI  - Response of cyclin B1 to ionizing radiation: regulation by NF-kappaB and
      mitochondrial antioxidant enzyme MnSOD.
AB  - BACKGROUND: To understand the molecular response of tumor cells to therapeutic
      ionizing radiation (IR), we previously reported that human breast cancer cells
      derived following chronic exposure to fractionated ionizing radiation (MCF+FIR)
      showed a transient radioresistance. MCF+FIR cells also demonstrated increased
      activity of NF-kappaB, increased expression of the mitochondrial antioxidant
      enzyme (MnSOD), and increased expression of a cell cycle regulatory protein
      (Cyclin B1). The present studies were designed to determine the relationship of
      NF-kappaB, MnSOD and Cyclin B1 expression in cellular adaptive responses to
      ionizing radiation. MATERIALS AND METHODS: The first intron of the cyclin B1 gene
      with a putative NF-kappaB element was cloned into the pGL3 luciferase reporter
      (pGL3CB1EI1). PGL3CB1EI1 and control NF-kappaB luciferase activities were
      determined in MCF-7 and MCF+FIR cells treated with a single dose of radiation,
      over expression of the dominant negative mutant IkB (mIkB) or over expression of
      the SOD2 gene. RESULTS: MCF+FIR cells derived from fractionated IR demonstrated
      increased transactivation of the pGL3CB1EI1 and NF-kappaB controlled reporter
      activities, relative to the parental cell line. Transfection of dominant negative
      mutant IkB that inhibits NF-kappaB nuclear translocation, inhibited pGL3CB1EI1
      and NF-kappaB activity, indicating the NF-kappaB dependence of pGL3CB1EI1
      mediated transcription. In addition, over expression of the human SOD2 gene
      (MnSOD) inhibited NF-kappaB and pGL3CB1EI1 activity, indicating that superoxide
      or some species derived from superoxide may have participated in the up
      regulation of reporter activity in response to chronic exposure to fractionated
      ionizing radiation. These results provide evidence suggesting that a signaling
      pathway involving NF-kappaB and Cyclin B1 may contribute to adaptive
      radioresistance induced by chronic exposure to fractionated IR and support the
      conclusion that MnSOD appears to be a negative regulator of this pathway.

PMID- 15517871
TI  - Generation of a humanized monoclonal antibody against human parathyroid hormone
      related protein and its efficacy against humoral hypercalcemia of malignancy.
AB  - A humanized monoclonal antibody against parathyroid hormone-related protein
      (PTHrP) was generated from the mouse monoclonal antibody raised against the
      peptide corresponding to the N-terminal 34 amino acids of the human PTHrP
      [(PTHrP(1-34)]. The humanized antibody interacted with the PTHrP(1-34) with a kD
      value of 1.90 x 10(-10) M, and the epitope resides between the amino acids 20 and
      30 of the PTHrP. PTHrP(1-34) significantly increased the intracellular cAMP
      levels in the rat osteosarcoma cells that expressed PTHR1, and the 5 microg/mL or
      higher concentrations of the humanized antibody almost completely blocked the
      PTHrP-induced cAMP production even in the presence of 2 microg/mL PTHrP(1-34),
      demonstrating its ability to fully neutralize PTHrP function. There was no
      significant difference in the potency of the mouse, chimera, or the humanized
      antibodies to suppress the PTHrP-induced increase in the intracellular cAMP in
      ROS cells. Furthermore, at the same doses, the administration of the chimera or
      the humanized antibody was equally effective in reducing the blood ionized
      calcium levels of hypercalcemic mice bearing the PAN-7-JCK human pancreatic
      cancer xenograft or the LC-6-JCK human lung cancer xenograft that secreted PTHrP.
      Thus, humanized anti-PTHrP may be useful for the treatment of the humoral
      hypercalcemia of malignancy in humans.

PMID- 15517872
TI  - Inhibitory effect of STI571 on cell proliferation of human malignant fibrous
      histiocytoma cell lines.
AB  - BACKGROUND: Malignant fibrous histiocytoma (MFH) is one of the most common high
      grade sarcomas in bone and soft tissue and, due to its chemo-resistance, the
      prognosis of the disease is poor. ST1571 is a tyrosine kinase inhibitor that was
      initially developed as a BCR/ABL inhibitor for chronic myeloid leukemia patients.
      STI571 also selectively inhibits platelet-derived growth factor receptors
      (PDGFRs) and c-kit. We examined the expression of PDGFRs and c-kit in human MFH
      cell lines, and the effect of STI571 on cell proliferation. MATERIALS AND
      METHODS: Four human MFH cell lines (TNMY1, GBS-1, Nara-F and Nara-H) were used.
      mRNA expression of the receptor tyrosine kinases (PDGFRs and c-kit) was analyzed
      using reverse transcription-polymerase chain reaction, and the inhibitory effect
      of STI571 on cell proliferation was analyzed using the MTS assay technique.
      RESULTS: PDGFRalpha mRNA was expressed in TNMY1 and GBS-1, and PDGFRbeta and c
      kit mRNAs were expressed in TNMY1, GBS-1 and Nara-F. All three of these mRNAs
      were absent in Nara-H. STI571 inhibited cell proliferation of TNMY1, GBS-1 and
      Nara-F in a dose- and time-dependent manner, but cell proliferation of Nara-H was
      not inhibited by ST1571 at concentrations of 10 microM or less. CONCLUSION:
      STI571 significantly inhibited proliferation of the three human MFH cell lines
      that expressed mRNAs of target receptor tyrosine kinases. The inhibitory effect
      of ST1571 on cell proliferation in these three cell lines might be due to
      decreased tyrosine kinase activity. STI571 might be a potent chemotherapeutic
      agent for human MFHs.

PMID- 15517873
TI  - In vivo adriamycin-induced apoptosis in peritoneal murine macrophages: partial
      participation of a caspase cascade.
AB  - BACKGROUND: Adriamycin (ADM) is a potent antitumor drug that induces apoptosis
      (AP) in tumor cells. AP is modulated by caspases and by mitogen-activated protein
      kinases (MAPK) as well as by the mitochondrial membrane potential (deltapsim). We
      studied the participation of these systems in peritoneal macrophages from ADM
      treated mice. MATERIALS AND METHODS: Balb/c mice were either treated with ADM (5
      mg/kg, i.p.) or with 0.85% NaCl solution (controls). One hour later, peritoneal
      cells were harvested and cultured for 28 h. AP was evaluated by ethidium bromide
      and acridine orange staining; deltapsim was monitored using a MitoCapture stain
      Kit; DNA integrity was assessed by electrophoretic analysis. Animals were treated
      (i.p.) 1 h before ADM administration with Z-LEHD-FMK, Z-DEVD-FMK, or Z-VAD-FMK
      (caspase-9, caspases-3, 7,10 and general caspase inhibitors, respectively) or
      with PD169316 (a MAPKp38 inhibitor). RESULTS: ADM induced a higher rate of AP and
      the characteristic electrophoretic DNA ladder pattern. Mice treated with caspases
      inhibitors plus ADM showed significant reductions in AP and DNA laddering; in
      contrast, no differences were observed in mice treated with PD169316 plus ADM in
      comparison with ADM alone. ADM also induced early loss of the deltapsim.
      CONCLUSION: In these experimental conditions, ADM induced AP in a mainly caspase
      9-dependent manner and this was related to a reduction in the deltapsim.

PMID- 15517874
TI  - Rapamycin inhibits Akt-mediated oncogenic transformation and tumor growth.
AB  - Akt is a serine/threonine kinase that plays a critical role in cell survival and
      proliferation. Three isoforms of Akt have been identified and have been shown to
      be up-regulated in human malignancies. We examined the requirement of these
      pathways for Akt transformation. We generated NIH-3T3 cells over-expressing
      constitutively active Myr-Akt1 (3T3-Akt1 cells) or Myr-Akt2 (3T3-Akt2 cells).
      These cells are able to form colonies in soft-agar and 3T3-Akt1 cells formed
      tumors in SCID mice. Rapamycin efficiently inhibited the activation of the mTOR
      p70S6K pathway and the anchorage-independent growth of both 3T3-Akt cells,
      demonstrating the importance of the mTOR-p70S6K pathway for transformation by
      Akt1 as well as by Akt2. Moreover, rapamycin dramatically inhibited the tumor
      formation by 3T3-Akt1 cells in SCID mice. Thus, we demonstrated the importance of
      mTOR-p70S6 kinase pathway in the transformation by Akt, both in tissue-cultured
      cells and in animal tumor models. In contrast, neither the MAPK pathway nor the
      p38 MAPK pathway is required for Akt-dependent transformation of NIH3T3 cells.

PMID- 15517875
TI  - Depsipeptide enhances imatinib mesylate-induced apoptosis of Bcr-Abl-positive
      cells and ectopic expression of cyclin D1, c-Myc or active MEK abrogates this
      effect.
AB  - BACKGROUND: Imatinib mesylate (ST1571) is the first-line drugfor chronic myeloid
      leukemia (CML), but development of resistance to this drug is a clinical problem.
      To explore the effective use of ST1571, we studied the combination treatment with
      histone deacetylase inhibitor (depsipeptide, FK228). MATERIALS AND METHODS: FK228
      and trichostatin A (TSA) were studied with respect to apoptosis of two Bcr-Abl
      positive cell lines, K562 and TCC-S. Genetically-modified K562 cells by any of
      cyclin D1, c-Myc and active MEK genes were also studied. Apoptosis was examined
      by nuclear-morphology under a fluorescent microscope and by the expression of
      annexin V Changes of apoptosis-regulating genes and acetylated histone H4 were
      studied by immunoblot. RESULTS: FK228 showed cytotoxicity at the nano-molar
      level. Combination treatment with STI571 and FK228 enhanced the induction of
      apoptosis significantly compared with each single treatment, although the histone
      acetylation level was not changed by the co-treatment. The combination treatment
      activated caspase-3 and cleaved PARP, but it did not induce any notable change in
      the expression of Bcl-XL, Bcl-2 and Bax compared with each single treatment.
      Enhanced apoptosis by the co-treatment was abrogated by ectopic expression of
      cyclin D1, c-Myc or active MEK CONCLUSION: The combination of FK228 with STI571
      is a promising treatment for Bcr-Abl-positive CML, but the activation of the
      MEK/ERK pathway and its downstream target genes may bring resistance to the co
      treatment in leukemic cells.

PMID- 15517876
TI  - Expression of CD40 ligand in CD40-positive murine tumors activates transcription
      of the interleukin-23 subunit genes and produces antitumor responses.
AB  - CD40-positive dendritic cells (DCs) are stimulated with CD40 ligand (CD40L) and
      subsequently secrete a number of cytokines including interleukin (IL)-23, which
      is involved in cell-mediated immune responses. Expression of CD40 ligand (CD40L)
      on tumors can activate host immune systems and produce antitumor effects against
      the tumors. We examined a possible mechanism of the antitumor responses: tumor
      cells expressing CD40 can transcribe DCs-derived cytokine genes by the expressed
      CD40L. For the purpose, CD40-positive A11 and -negative P29 murine lung tumors
      cells, both of the same origin, were transfected with the CD40L gene (A11/CD40L
      and P29/CD40L). The growth rate in vitro of A11/CD40L and P29/CD40L cells was not
      different from that of the respective parent tumors; however, the growth in vivo
      of A11/CD40L tumors in syngeneic mice was significantly retarded and the growth
      retardation of P29/CD40L tumors was marginaL Transcription of the p40 and p19
      genes, IL-23 subunit genes, was up-regulated in A11/CD40L cells compared with
      parent A11 cells, whereas this up-regulation was not observed in P29/CD40L cells.
      Since expression of IL-23 in tumors can produce antitumor effects, the present
      data suggest that the CD40/CD40L interaction can activate cytokine transcripts in
      certain tumors and consequently contribute to antitumor responses.

PMID- 15517877
TI  - Inhibition or promotion of tumor growth by granulocyte-macrophage colony
      stimulating factor derived from engineered tumor cells is dose-dependent.
AB  - BACKGROUND: Granulocyte-macrophage colony stimulating factor (GM-CSF) has been
      widely investigated as an adjuvant factor for tumor immunotherapy. However, the
      results are controversial with antitumor effects in some studies and a tumor
      growth promotion effect in others. MATERIALS AND METHODS: In order to determine
      whether there is a dose-dependent effect of GM-CSF on tumor growth, murine GM-CSF
      expressing vector was constructed and transfected into TC-1 tumor cells and
      various clones stably expressing different levels of GM-CSF were obtained. The
      growth of these clones in vivo was studied. RESULTS: Although these clones grow
      at a similar rate in vitro, their growth in vivo is dramatically different.
      Clones expressing high levels (>10,000 pg/ml) of GM-CSF grow significantly faster
      than the control (p <0.001); clones expressing low levels (<100 pg/ml) of GM-CSF
      grow significantly slower than the control (p<0.001); while clones expressing
      intermediate levels (1000-2000 pg/ml) of GM-SCF grow at a similar rate as the
      control (p >0. 05). The high levels of GM-CSF secreted by tumor cells induced
      granulocytosis and lymphopenia. The antitumor growth effect induced by low levels
      of GM-CSF is not due to the function of lymphocytes. CONCLUSION: The inhibition
      or promotion of tumor growth by GM-CSF secreted from tumor cells is dose
      dependent.

PMID- 15517878
TI  - Cyclooxygenase-2 gene induction causes CDDP resistance in colon cancer cell line,
      HCT-15.
AB  - Drug resistance to cisplatin (CDDP) would represent a major obstacle for cancer
      therapy. The adenosine triphosphate (ATP) binding cassette (ABC) family of
      transport proteins, such as the 170 kDa P-glycoprotein (multidrug resistance gene
      1; MDR-1) and the 190 kDa multidrug resistance-associated proteins (MRPs), are
      associated with multidrug resistance, including resistance to CDDP. The purpose
      of the present study was to investigate the relationship between cyclooxygenase-2
      (COX-2) expression and the level of chemosensitivity to CDDP. We established the
      COX-2-overexpressed colon cancer cell line TR-5 from HCT-15 cells. We quantified
      the expression of m-RNA for MRP-1 and MDR-1 by a real-time PCR method,
      determining that the values of each gene/standardized GAPDH in HCT-15 and TR-5
      were 23+/-0.4 and 6.1+/-0.5 in MRP-1 (p<0.02) and 9.0+/-4.8 and 3.6+/-0.5 in MDR
      1, respectively. With respect to chemosensitivity, survival rates for 3 microg/ml
      and 10 microg/ml of CDDP were 81.5+/-12.2% and 26.1+/-11.7% (IC50=6.5 microg/ml)
      for HCT-15 and 96.6+/-1.7% and 77.4+/-4.9% (IC50=18.5 microg/ml) for TR-5,
      respectively, thus TR-5 showed higher resistance to CDDP than HCT-15 did with
      statistical differences. We also demonstrated a successful re-sensitization to
      CDDP toxicity in TR-5 by means of the COX-2 selective inhibitor JTE-522, 4-(4
      cyclohexyl-2-methyl-1, 3-oxazol-5-yl)-2-fluorobenzene sulfonamide, which markedly
      decreased the IC50 of CDDP for TR-5 (from 17.3+/-2.6 microg/ml to 8.6+/-2.5
      microg/ml). In conclusion, COX-2 overexpression induced increased MRP-1
      expression in a colon cancer cell line, TR-5, resulting in chemoresistance to
      CDDP that was approximately triple the level of chemoresistance observed in the
      original HCT-15 cells line, as measured by calculation of the IC50. We also
      confirmed the efficacy of pretreatment of TR-5 cells with the COX-2 selective
      inhibitor JTE-522 in restoring chemosensitivity of these cells to CDDP,
      suggesting a strategy for overcoming drug resistance to CDDP.

PMID- 15517879
TI  - Apoptosis-related gene expression affected by a GnRH analogue without induction
      of programmed cell death in LNCaP cells.
AB  - BACKGROUND: In this study we confirmed the ability of a Gonadotropin Releasing
      Hormone (GnRH) agonist, leuprorelin acetate (LA), to counteract or even suppress
      the 5alpha-dihydrotestosterone (DHT)-stimulated growth of androgen-sensitive
      prostate cancer cells (LNCaP). Since the cellular mechanisms mediating this
      effect are not well defined, we investigated the activity of LA, also in
      combination with DHT or with cyproterone acetate (CA), on the expression of genes
      (bcl-2, bax, c-myc) which may contribute to the proliferative behaviour of LNCaP
      cells. In addition, experiments aimed to evaluate the action of the analogue on
      apoptosis were performed. MATERIALS AND METHODS: Gene expression was evaluated by
      RT-PCR and Western blotting on cells treated with LA (10(-11) or 10(-6) M), alone
      or combined with 10(-9) M DHT or 10(-7) M CA. The occurrence of apoptosis
      following treatment with LA (10(-11), 10(-6) or 10(-5) M), alone or combined with
      10(-9) M DHT, was assessed by DNA fragmentation analysis. RESULTS: Both the mRNA
      and protein of the anti-apoptotic gene bcl-2 were induced (30-125%) by DHT after
      24-144 h. LA decreased bcl-2 mRNA (10-40%), while it did not unequivocally affect
      protein expression. The analogue always reduced (13-74%) both mRNA and protein
      levels obtained under DHT treatment. The mRNA and protein of the pro-apoptotic
      gene bax were down-regulated by DHT (15-40%), while LA generally induced bax
      protein but not its mRNA. LA counteracted DHT activity, even increasing bax
      protein levels over the controls. c-myc mRNA and protein were enhanced by DHT (15
      45%) but down-regulated by LA (10-40%). Once more, the androgen effect was
      antagonized by LA, sometimes reducing c-myc content below the controls. CA
      produced the most similar effects to those triggered by DHT. The hormonal
      treatment did not induce any DNA fragmentation. CONCLUSION: In spite of gene
      modulation, apoptosis was not observed under LA treatment, in agreement with the
      lack of a cell growth effect when the analogue was used alone. Nevertheless, the
      observed changes in gene expression may be directly or indirectly involved in the
      antiproliferative effect of LA on androgen-stimulated cells.

PMID- 15517880
TI  - Role of enzymatically inactive procathepsin D in lung cancer.
AB  - Procathepsin D is over-secreted by some human cancer cells. This enzymatically
      inactive precursor has been established as playing an important role in the
      development of several types of cancer. In the present investigation, we used
      both the isolated human procathepsin D and a synthetic 44 amino acid peptide
      corresponding to the activation peptide of procathepsin D to test their effects
      on the proliferation of lung cancer cells. We showed that both the procathepsin D
      and the activation peptide act as growth factors. In parallel, we also measured
      the secretion of procathepsin D by lung cancer cells and compared the secretion
      with invasiveness through Matrigel membrane. Our findings represent the first
      experimental data showing the direct effects of procathepsin D and its activation
      peptide on growth and invasiveness of lung cancer cells.

PMID- 15517881
TI  - Alteration of the vascular endothelial growth factor and angiopoietins-1 and -2
      pathways in transitional cell carcinomas of the urinary bladder associated with
      tumor progression.
AB  - Neoangiogenesis is assumed to play an important role in the progression,
      metastasis and prognosis of a wide variety of tumors. To get insights into the
      molecular-genetic pathways and the biological role of angiogenesis in urothelial
      carcinogenesis, we analyzed comparatively the expression of the mRNA of the
      vascular endothelial growth factor (VEGF) and of the angiopoietins-1 and -2 (Ang
      1 and Ang-2) in 71 transitional cell carcinomas (TCC) of the urinary bladder in
      relation to the tumor grades and stages, and referring to epidemiological risk
      factors. Using real-time quantitative reverse transcription-polymerase chain
      reaction, low-stage superficial TCC expressed VEGF and Ang-2 mRNA at a
      significantly higher level than high-stage muscle invasive carcinomas, and low
      grade TCC at an insignificantly higher level than high-grade tumors. The activity
      of both angiogenic factors was found to be significantly correlated. Conversely,
      Ang-1 mRNA was expressed at a 3-fold significantly lower level in low-grade, low
      stage compared to high-grade, high-stage TCC. A significantly 3- and 2-fold
      respectively, drop of the VEGF and Ang-2 mRNA expression in conjunction with a 2
      fold significantly higher expression of Ang-1 mRNA in the group of grade 2 TCC
      when infiltrating the muscle layer may represent a crucial event during
      urothelial carcinogenesis, and possibly indicates an important step in promoting
      the conversion of bladder cancer from a low to a high malignancy in this subset
      of carcinomas. By immunhistochemistry, high-grade, high-stage carcinomas less
      frequently displayed areas with a strong reactivity for the VEGF protein ('hot
      spots") than low-grade, low-stage TCC, paralleling the expression of the mRNA.
      The expression patterns observed are compatible with a reduced vascular
      destabilization and decreased formation of new blood vessels in advanced TCC,
      suggesting a balance between vessel regression and vascular growth, with a less
      pronounced vascular remodeling during late phases of urothelial carcinogenesis.
      Analyzing the effect of life-style bladder cancer risk factors, habitual smoking
      and coffee consumption was not observed to substantially alter the expression of
      the angiogenic mediators, except for weakly elevated levels of VEGF and Ang-2
      mRNA in TCC of strong smokers and a borderline significantly decreased VEGF mRNA
      expression associated with heavy coffee consumption. Certain hazardous
      occupational exposures (polycyclic hydrocarbons, paints and lacquer, stone dust)
      may play a role in modulating tumor angiogenesis. The current data indicate that
      the signaling molecular-genetic pathways underlying vascular remodeling are
      involved in the progression of urinary bladder cancer to a more malignant and
      aggressive behaviour.

PMID- 15517882
TI  - A new method of thermoablation with hot water vapour for localized tumours.
AB  - BACKGROUND: A new method of thermoablation with hot water vapour based on a new
      type of microtube was developed. This approach allows tumours, with volume and
      anatomical positions not accessible to other techniques (cryoablation,
      radiofrequency ablation, laser ablation) to be treated. MATERIALS AND METHODS:
      The method was tested on a human colon carcinoma grafted subcutaneously in Swiss
      nude mice and the experiment monitored under magnetic resonance imaging. RESULTS:
      It was found that 2.52 cal s(-1) per cm3 of tumour were necessary to reduce
      tumour size. The microtube is built to withstand a large range of temperatures
      and pressures and is biocompatible. CONCLUSION: A specific feature of this
      technique is that, besides hot vapour, several types of drugs can be delivered
      through the same microtube depending of the location, type or size of the tumour.
      These properties make it a unique device for multi-therapeutic treatments.

PMID- 15517883
TI  - Inhibition of cell proliferation by potential peroxisome proliferator-activated
      receptor (PPAR) gamma agonists and antagonists.
AB  - This study was initiated to determine if potential PPAR gamma antagonists could
      block the inhibition of cell proliferation caused by 4-phenylbutyrate. The action
      of 4-phenylbutyrate differed from other PPAR gamma ligands examined in that it
      induces histone acetylation. Proliferation of DS19 mouse erythroleukemia cells
      was inhibited by PPAR gamma agonists (4-phenylbutyrate, rosiglitazone,
      ciglitazone and GW1929) and by potential PPAR gamma antagonists: BADGE (Biphenol
      A diglycidyl ether), GW9662, PD068235 and diclofenac. Combined incubations tended
      to exhibit additive inhibitory effects. Potential PPAR gamma agonists and
      antagonists inhibited the incorporation of thymidine into DNA of human prostate
      (PC3), colon (Caco-2) and breast (T47D) cancer cells but also affected NIH3T3
      cells that have little or no expression of PPAR gamma. Lipid accumulation in T47D
      cells was seen after incubation with 4-phenylbutyrate and both potential PPAR
      gamma agonists and antagonists. The extent to which the effects of 4
      phenylbutyrate on cell proliferation are mediated through PPAR gamma or induction
      of histone acetylation remains an open question. We conclude that potential PPAR
      gamma antagonists may fail to reverse the growth inhibitory effect of PPAR gamma
      ligands and may themselves act as growth inhibitory agents.

PMID- 15517884
TI  - Activated Akt-1 in specific cell populations during multi-stage skin
      carcinogenesis.
AB  - The goal of the present study was to identify specific populations of cells that
      contain activated Akt-1, as determined by the presence ofphosphorylated Akt at
      serine 473 (p Akt), during development of skin tumors using a murine multi-stage
      carcinogenesis model. Nucleated papillomas cells as well as both epidermal and
      follicular keratinocytes in hyperplastic skin contained increased pAkt compared
      to skin treated only with acetone or 7, 12 dimethylbenz[a]anthracene (DMBA).
      Although the numbers of both mast cells and neutrophils were significantly
      increased in the stroma of papillomas (p<0.0005; p<0.0001, respectively), only
      mast cells contained pAkt. The amount of total Akt protein was similar regardless
      of time or treatment group examined. The present results suggest that activation
      of Akt-1 may provide specific populations of epidermal keratinocytes that develop
      into skin tumors with the ability to resist terminal differentiation and have
      enhanced proliferation during multi-stage skin carcinogenesis. In addition, mast
      cells which contain activated Akt-1 may persist within the stroma of papillomas
      during skin tumor development and progression through this signaling pathway,
      thereby contributing to a pro-oxidant and proangiogenic microenvironment.

PMID- 15517885
TI  - Role of resveratrol in prevention and therapy of cancer: preclinical and clinical
      studies.
AB  - Resveratrol, trans-3,5,4'-trihydroxystilbene, was first isolated in 1940 as a
      constituent of the roots of white hellebore (Veratrum grandiflorum O. Loes), but
      has since been found in various plants, including grapes, berries and peanuts.
      Besides cardioprotective effects, resveratrol exhibits anticancer properties, as
      suggested by its ability to suppress proliferation of a wide variety of tumor
      cells, including lymphoid and myeloid cancers; multiple myeloma; cancers of the
      breast, prostate, stomach, colon, pancreas, and thyroid; melanoma; head and neck
      squamous cell carcinoma; ovarian carcinoma; and cervical carcinoma. The growth
      inhibitory effects of resveratrol are mediated through cell-cycle arrest;
      upregulation of p21Cip1/WAF1, p53 and Bax; down-regulation of survivin, cyclin
      D1, cyclin E, Bcl-2, Bcl-xL and clAPs; and activation of caspases. Resveratrol
      has been shown to suppress the activation of several transcription factors,
      including NF-kappaB, AP-1 and Egr-1; to inhibit protein kinases including
      IkappaBalpha kinase, JNK, MAPK, Akt, PKC, PKD and casein kinase II; and to down
      regulate products of genes such as COX-2, 5-LOX, VEGF, IL-1, IL-6, IL-8, AR and
      PSA. These activities account for the suppression of angiogenesis by this
      stilbene. Resveratrol also has been shown to potentiate the apoptotic effects of
      cytokines (e.g., TRAIL), chemotherapeutic agents and gamma-radiation.
      Phamacokinetic studies revealed that the target organs of resveratrol are liver
      and kidney, where it is concentrated after absorption and is mainly converted to
      a sulfated form and a glucuronide conjugate. In vivo, resveratrol blocks the
      multistep process of carcinogenesis at various stages: it blocks carcinogen
      activation by inhibiting aryl hydrocarbon-induced CYP1A1 expression and activity,
      and suppresses tumor initiation, promotion and progression. Besides
      chemopreventive effects, resveratrol appears to exhibit therapeutic effects
      against cancer. Limited data in humans have revealed that resveratrol is
      pharmacologically quite safe. Currently, structural analogues of resveratrol with
      improved bioavailability are being pursued as potential therapeutic agents for
      cancer.

PMID- 15517886
TI  - Re-distribution of tenascin-C in the parotid acinar cells. An early marker of
      radiation-induced damage of salivary glands?
AB  - PURPOSE: In order to investigate the early changes in the expression of tenascin
      C, following irradiation and the associated functional impairment of salivary
      glands. MATERIALS AND METHODS: Fifteen rabbits were used for the study. Five
      provided control parotid gland tissue and a further 10 rabbits were
      scintigraphically examined prior to and 24 h after 15/30 Gy. Glands were studied
      histologically using HE-staining and tenascin-C antibodies. RESULTS: Reduction in
      the salivary ejection fraction (SEF) was observed in all irradiated glands.
      Simultaneously, a marked re-distribution of tenascin-C expression was noticed.
      Reactivity detected in the intercalated, secretory ducts and perineurinal regions
      prior to radiation was noticed intracellularly after 24 h. Furthermore, nerves
      showed tenascin-C expression in the Schwann cells, but no longer perineurinally.
      Myofibroblasts were also observed in the stroma. CONCLUSION: This study proves
      the ability to predict functional disorders of salivary function as early as 24 h
      after radiation and provides evidence of the participation of tenascin-C in the
      pathological process of radiation-induced damage in salivary glands.

PMID- 15517887
TI  - Activity of cathepsin B and D in colorectal cancer: relationships with tumour
      budding.
AB  - It has been reported that poorly-differentiated clusters of cancer cells at the
      invasive front, namely "tumour budding", may reflect malignancy of colorectal
      cancer. The aim of the present study was to evaluate the activity of cathepsin D
      and B in tumours and in normal mucosa from pT3 and G2 colorectal cancers, and to
      analyse their association with tumour budding at the invasion front of colorectal
      cancer. PATIENTS AND METHODS: A total of 40 patients classified as pT3, G2
      underwent curative resection of colon cancer between 1997 and 2001. The fragments
      of tumours and normal colorectal tissue were obtained for biochemical
      examinations. We also categorized tumour budding (TB) at the front of invasion.
      Two groups were used for classification of the TB phenomenon: the first where no
      bud was observed- TB(-), and the second where at least one bud was found -TB(+)
      at the front of invasion in the examined slice. RESULTS: The activity of
      cathepsins D and B was found to be statistically significantly higher both in the
      neoplastic tissue cytosol and homogenate, compared to the cytosol and homogenate
      of adjacent healthy tissue (p<0.05). There was, however, no significant
      difference between tumour budding and the activity of cathepsin D in tumour
      tissue, but we found a statistically significant difference between the activity
      of cathepsin B in the homogenate and cytosol of tumour tissue and budding
      positive tumours (p=0.027, p=0.004, respectively). CONCLUSION: These results
      suggest that the activity of cathepsin D is not involved in tumour budding. In
      our opinion, much more attention should be paid to cathepsin B, as a potentially
      responsible factor in tumour progression, since it strongly increased with the
      presence of tumour budding.

PMID- 15517888
TI  - Immunocytochemical and pharmacological characterisation of P2-purinoceptor
      mediated cell growth and death in PC-3 hormone refractory prostate cancer cells.
AB  - BACKGROUND: Extracellular nucleotides (e.g adenosine 5'-triphosphate, ATP)
      influence biological processes via purinergic receptors. We characterised the P2
      purinoreceptors in human hormone refractory prostate cancer (HRPC) cells (PC-3
      cells). RESULTS: 1. Immunofluorescent staining demonstrated P2X3 P2X, P2X5 P2X7
      and P2Y2 receptors. 2. ATP inhibited cell growth by up to 91% over 72h.
      Pharmacological characterisation indicated a P2X-purinoreceptor-mediated
      response. 3. Comparable maximum growth inhibition was seen after either a single
      addition of 1mM or daily addition of 100mM ATP. ATP concentrations ([ATP])
      returned to baseline levels within 24h if the initial [ATP] was < or =100 HM,
      while [ATP] remained high for 72h if a single concentration of 1 mM was used. 4.
      ATP 1 mM significantly (p<0.001) increased the proportion of cells undergoing
      apoptosis from 0.27% (+/- 0.04%) to 5.28% (+/- 0.77%). CONCLUSION: Threshold
      concentrations of ATP inhibited HRPC cell growth in vitro via the activation of
      P2X-purinoreceptors. The role of nucleotides in the treatment of HRPC requires
      further investigation.

PMID- 15517889
TI  - Immunotherapy by gene transfer with plasmids encoding IL-12/IL-18 is superior to
      IL-23/IL-18 gene transfer in a rat osteosarcoma model.
AB  - BACKGROUND: Osteosarcomas are primary malignant tumors of bone or soft parts
      arising from bone-forming mesenchymal cells. Despite dramatic therapeutic
      advances, namely neo-adjuvant and adjuvant chemotherapy, progress is at a
      plateau. Cytokine-mediated gene therapy might represent a further advance in the
      therapy of the osteosarcoma. MATERIALS AND METHODS: We transfected UMR 108
      osteosarcoma cells with different plasmids encoding IL-12, IL-23, proIL-18 and
      ICE (Interleukin-converting enzyme). IFN-gamma induction, which is known to
      induce antitumor effects mediated by the immune system, and cytotoxic effects of
      various cytokine combination were investigated. RESULTS: Our results show that
      local secretion of IL-12 by UMR 108 cells led to an induction of cytotoxic
      effects mediated by mononuclear cells, which were enhanced by additional
      administration of recombinant IL-18. In contrast to IL-18, IL-23 showed a
      moderate increase of IFN-gamma induction when transfected alone and could only
      slightly increase the IFN-gamma induction mediated by IL-12. IL-18 enhanced IFN
      gamma induction when applied alone and was able to increase the IFN-gamma
      production that was induced by IL-12. CONCLUSION: IL-23 seems to be a less
      effective immuno-therapeutic for adjuvant treatment of osteosarcomas than IL-12
      and IL-18, when taking only IFN-gamma induction into consideration.

PMID- 15517890
TI  - Carboxyamido-triazole (CAI), a signal transduction inhibitor induces growth
      inhibition and apoptosis in bladder cancer cells by modulation of Bcl-2.
AB  - Pro- and anti-apoptotic factors and intracellular signaling pathways are targets
      for therapeutic development of anticancer agents. Carboxyamido-triazole (CAI) is
      an inhibitor of transmembrane calcium influx and intracellular calcium-requiring
      signal transduction pathways. The present study investigates the effects of CAI
      on human transitional cancer cell (TCC) viability and apoptosis, and evaluates
      whether apoptotic resistance may be overcome pharmacologically. Both well
      differentiated (RT4, RT112/grade 1) and poorly-differentiated (T24/grade 3;
      SUP/grade 4) human TCC lines were shown to express Fas. Upon exposure to
      agonistic monoclonal Fas antibody, only well-differentiated TCC lines underwent
      apoptotic cell death. CAI exposure reduced cell viability and caused an at least
      additive anti-apoptotic effect in combination with the Fas antibody in the Fas
      insensitive TCC lines. Under the same conditions under which CAI treatment
      augmented Fas-mediated apoptosis, it was shown to reduce intracellular bcl-2
      quantity. This response to CAI indicates that apoptotic cell death is enhanced by
      the reduction of bcl-2 protein expression. We suggest that the antitumor effect
      of CAI is at least partially based on restoring a pathway of apoptosis. It may
      cause transformation of cell homeostasis that leads to the alteration of
      apoptotic mechanisms, thus allowing highly malignant tumor cells to re-enter the
      physiological course of cell elimination.

PMID- 15517891
TI  - Sasa health exerts a protective effect on Her2/NeuN mammary tumorigenesis.
AB  - Bamboo grass leaves of different Sasa species have been widely used in food and
      medicine in Eastern Asia for hundreds of years. Of special interest are Kumazasa
      (Sasa senanensis rehder) leaves used to prepare an alkaline extract known as Sasa
      Health. This extract was reported to inhibit both the development and growth of
      mammary tumors in a mammary tumor strain of virgin SHN mice (1). We found that
      Sasa Health exerts a significant protective effect on spontaneous mammary
      tumorigenesis in another mouse model of human breast cancer, the transgenic FVB
      Her2/NeuN mouse model. Two cohorts of Her2/NeuN female mice of different age
      (eleven-week-old and twenty-four-week-old) chronically treated with Sasa Health
      in drinking water showed both a delay in the development of tumors and reduced
      tumor multiplicity. Sasa Health also induced inhibition of mammary duct branching
      and side bud development in association with reduced angiogenesis. Altogether
      these findings indicate that Sasa Health contains phytochemicals that can
      effectively retard spontaneous mammary tumorigenesis.

PMID- 15517892
TI  - EGF-receptor related protein causes cell cycle arrest and induces apoptosis of
      colon cancer cells in vitro and in vivo.
AB  - BACKGROUND: EGF Receptor Related Protein (ERRP), a recently identified negative
      regulator of EGF-receptor (EGFR), has been shown to inhibit growth of colon
      cancer xenograft tumors in SCID mice. However, the mechanisms by which ERRP
      exerts its anti-tumor properties are poorly understood The current investigation
      was undertaken to delineate the inhibitory mechanisms that are triggered by ERRP.
      MATERIALS AND METHODS: For in vivo experiments, recombinant ERRP (20
      microg/mouse) or an equivalent volume of vehicle was injected (away from the
      tumor site) every other day for 10 days to SCID mice xenotransplanted with the
      colon cancer cell line HCT-116 Tumor explants were obtained for further
      immunohistochemical analysis. For in vitro studies, the HCT-116 cell line was
      incubated with recombinant ERRP and apoptosis markers and cell cycle changes were
      evaluated. RESULTS: Recombinant ERRP caused marked inhibition of tumor growth.
      This was accompanied by increased apoptosis and attenuation of ERK1/2 and Akt
      activities. Exposure of HCT-116 cells to recombinant ERRP for 24 hours caused
      apoptosis and cell cycle arrest at G0/1-phase. Induction of apoptosis was
      evidenced by increased levels of cleaved caspase-3, PARP proteins and acridine
      orange staining. CONCLUSION: Our findings reveal a pro-apoptotic property of ERRP
      both in vitro and in vivo. We propose that ERRP functions by inhibiting the
      activation of the EGF-receptor signaling and its downstream effectors such as ERK
      and Akt kinases, underscoring the potential of ERRP for the treatment of
      colorectal cancer where the EGF pathway is known to be activated.

PMID- 15517893
TI  - UGT1A10 is responsible for SN-38 glucuronidation and its expression in human lung
      cancers.
AB  - BACKGROUND: We previously reported that upregulation of glucuronidation activity
      catalyzed by uridine 5'diphosphoglucuronosyltransferase (UGT) is one of the
      mechanisms associated with irinotecan hydrochloride/7-ethyl-10
      hydroaxycamptothecin (CPT-11/SN-38) resistance. In order to extend this result to
      the clinical setting, it is important to elucidate the role of SN-38
      glucuronidation by UGT1A isoforms in CPT-11/SN-38 resistance in vivo. MATERIALS
      AND METHODS: We examined SN-38 glucuronidation activity in COS-7 cells
      transfected with full-length cDNAs for human UGT isoforms (UGT1A1, UGT1A3, UGT1A6
      and UGT1A10). The gene expression levels of UGT isoforms were examined in lung
      cancer cell lines and 14 lung cancer samples by semi, quantitative RT-PCR.
      RESULTS: Our HPLC assay results showed that both UGT1A1 and UGT1A10 are
      responsible for SN-38 glucuronidation. The levels of UGT1A1 and UGT1A10
      expression in a CPT-11/SN-38-resistant cell line were increased compared to
      levels in the parent cell line. Furthermore, there was considerable intersubject
      variability in 14 lung cancer samples, but UGT1A1 and UGT1A10 expression levels
      were significantly correlated (r=0. 70, p=0.004). Our results suggest that not
      only UGT 1A1, but also UGT 1A10, plays an important role in detoxifying CPT-11/SN
      38, leading to resistance to CPT-11/SN-38 in lung cancer.

PMID- 15517894
TI  - High efficacy of docetaxel with and without androgen deprivation and estramustine
      in preclinical models of advanced prostate cancer.
AB  - BACKGROUND: To assess the activity of docetaxel in combination with hormonal
      therapy in preclinical models of prostate cancer. MATERIALS AND METHODS: Since
      prostate cancer has a predilection for the bone, we assessed the antitumor
      activity of docetaxel in in vivo models of both bone metastasis and localized
      prostate cancer, using MDA PCa 2b and PC3 cells in SCID mice. RESULTS: Dramatic
      antitumor efficacy was observed regardless of whether the tumor cells were
      implanted in the prostate or in the bone. Antitumor activity was also evident in
      both osteolytic and osteoblastic lesions. Reasoning that docetaxel efficacy might
      be enhanced if it were to be used earlier in the course of the disease, we
      studied the sequence of docetaxel and androgen ablation (part of standard
      treatment for early-stage prostate cancer) in the MDA PCa 2b xenograft model. The
      activity was similar whether docetaxel and androgen ablation were used alone,
      simultaneously, or in sequence, indicating a lack of synergism or antagonism.
      Finally, we studied the combination of docetaxel and estramustine on androgen
      sensitive and androgen-independent cell lines in vitro and in vivo. Estramustine
      did not increase the activity of docetaxel in these models. CONCLUSION: These
      results provide a strong preclinical rationale for the clinical development of
      docetaxel for the treatment of both locally advanced and disseminated prostate
      cancer.

PMID- 15517896
TI  - Selenium influences the radiation sensitivity of C6 rat glioma cells.
AB  - BACKGROUND: A radioprotective effect of low selenium doses on normal tissue and a
      possible radiosensitization of tumor cells at higher concentrations have been
      previously suggested. However, systematic experimental and clinical data are
      scarce. MATERIALS AND METHODS: C6 cells were cultured for 14 days at different
      selenite concentrations (0 microM, 2 microM, 3 microM and 3.6 microM) and
      irradiated with 0 Gy to 20 Gy. Plating efficiency and survival were determined
      using the colony assay. RESULTS: The overall radiosensitivity was low
      (D0,control=6.1 Gy). Irradiated cells exposed to increasing selenite
      concentrations showed a lower plating efficiency and, for doses > 2 Gy, a lower
      survival than the control. For Se concentrations of 0 microM, 2 microM and 3
      microM, respectively, SF2 amounted to 0.72, 0.48 and 0.46, and SF5 to 0.37, 0.25
      and 0.12. Student's t-test yielded a significant difference between the 0 microM
      and 3 microM curves at 5 Gy (p=0.02) and 10 Gy (p=0.009). CONCLUSION: Our
      experiments suggest a radiosensitizing effect of selenite in glioma cells at
      concentrations of 2-3 microM.

PMID- 15517895
TI  - Combination study of 1,24(S)-dihydroxyvitamin D2 and chemotherapeutic agents on
      human breast and prostate cancer cell lines.
AB  - BACKGROUND: Vitamin D compounds are important modulators of cellular
      proliferation and differentiation, with potential utility as anticancer drugs.
      1,24(S)-Dihydroxyvitamin D2 [1,24(OH)2D2] is a naturally occurring active vitamin
      D compound with low calcemic activity. MATERIALS AND METHODS: We evaluated the
      growth inhibitory effects of 1,24(OH)2D2 on LNCaP prostate cancer and MCF-7
      breast cancer cells. 1,24(OH)2D2 was evaluated alone and in paired combination
      with nine chemotherapeutic agents. Drug interactions were analyzed using the
      median-effect/isobologram method. Combination index values were used to
      characterize the interactions as synergistic, additive, or antagonistic. RESULTS:
      In MCF-7 cells, 1,24(OH)2D2 produced synergistic effects with doxonrubicin and
      cisplatin and additive effects with busulfan, etoposide, tamaxifen, 5
      fluorouracil and carboplatin. In LNCaP cells, 1,24(OH)2D2 produced a synergistic
      effect with carboplatin and additive effects with doxorubicin, busulfan,
      paclitaxel and etoposide. CONCLUSION: We conclude that 1,24(OH)2D2 may have
      therapeutic value in the treatment of prostate and breast cancers, alone or in
      combination with chemotherapeutic agents.

PMID- 15517897
TI  - Expression of estrogen receptor-beta isoforms in Barrett's metaplasia, dysplasia
      and esophageal adenocarcinoma.
AB  - We have previously shown that the majority of esophageal adenocarcinomas (EA),
      and its precursor Barrett's metaplasia (BM), express estrogen receptor beta (ER
      B). Several isoforms of ER-B have been described and are presumed to have
      different functions, but their distribution in BM and EA is not known. The aim of
      this work was to determine which ER-B isoforms are expressed in EA and BM.
      Sections of formalin-fixed and paraffin-embedded esophageal tissue from 33
      esophageactomy specimens, of which 27 had invasive EA, were stained for the ER-B
      isoforms ER-B1, ER-B2, ER-B3 and ER-B5 utilizing the immunoperoxidase method ER
      B1 was detected in 23 out of 27 (85%) EA compared to 3 out of 14 (21%) Barrett's
      metaplasia negative for dysplasia (BMND) (p =0. 0001); ER-B2 was expressed in 22
      out of 27 (81%) EA in contrast to 3 out of 14 (21%) BMND (p=0.0004); ER-B3 was
      positive in 27 out of 27 (100%) EA in contrast to only 1 out of 14 (7%) BMND
      (p<0001); ER-B5 was detected in 27 out of 27 (100%) EA compared to 9 out of 14
      (62%) of BMND (p=0.0027). High- and low-grade dysplasia showed a similar ER-beta
      isoform expression profile to that of EA Cancers invasive through the esophageal
      wall had a higher percent of cells with cytoplasmic expression of ER-B1 than
      tumors limited to the wall (T3 vs. T1 and T2, p=0.051). We conclude that ER-B1,
      ER-B2, ER-B3 and ER-B5 are overexpressed in EA compared to its precursor lesion
      BMND, suggesting a significant biological role for steroid hormones in EA.

PMID- 15517898
TI  - Methotrexate as a photosensitiser.
AB  - The absorption, excitation and emission spectra of methotrexate (MTX) solutions
      in natural saline water and sodium hydroxide at 10(-4)-10(-5) MpH=8.4 were
      measured, while they were exposed to coherent and uncoherent visible and near
      ultraviolet (UV) light. Xe and Hg lamp and also a nitrogen pulsed laser radiation
      were used. The absorption spectra exhibited spectral bands between 225 nm and 450
      nm. The 200 nm - 500 nm excitation spectra were measured with emission centred on
      470 nm; fluorescence excitation was observed at 340 nm and 370 nm; emission
      fluorescence was detected between 400 nm and 600 nm, showing a maximum at 470 nm.
      Spectra modifications, non-linearly depending on exposure time (varying from 3
      min to 180 min), indicated the photodissociation of MTX to the fluorescent
      compound 2,4 diamino-formylpteridine. In a preliminary in vivo experiment, rapid
      destruction of neovascularisation was observed in the MTX-impregnated conjunctive
      of the rabbit eye exposed to uncoherent UV and visible light.

PMID- 15517899
TI  - Multidrug resistance associated genes MRP1, MRP2 and MRP3 in primary and
      anthracycline exposed breast cancer.
AB  - BACKGROUND: Multidrug resistance associated proteins MRP1, MRP2 and MRP3 confer
      in vitro multidrug resistance. We investigated their role in breast cancer
      resistance to anthracycline-based chemotherapy. MATERIALS AND METHODS: Using real
      time reverse transcriptase polymerase chain reaction (RT-PCR) and
      immunohistochemistry (IHC), the expression of MRP1 - 3 was quantified in nine
      breast cancer cell lines and 30 breast carcinoma samples. RESULTS: MRP1 - 3 mRNA
      was detectable in all breast cancer cell lines and tumor samples. No increase of
      expression was detected between untreated carcinoma and post-neoadjuvant
      anthracycline treatment tumor samples. IHC failed to detect the proteins. MRP1 -
      3 expression was not associated with tumor response to treatment or with outcome.
      CONCLUSION: MRP1 - 3 are expressed in breast cancer cells, but are not detected
      with IHC. We have found no evidence linking these proteins to clinical drug
      resistance in a small but well-documented series of breast cancer samples.

PMID- 15517900
TI  - X-rays affect the expression of genes involved in angiogenesis.
AB  - BACKGROUND: We have previously shown, using the chicken embryo chorioallantoic
      membrane (CAM) model of in vivo angiogenesis, that X-rays act on the
      extracellular matrix and enhance normal and tumor-induced angiogenesis. In the
      present work, we studied the effect of X-rays on the gene expression of three
      proteins that are important regulators of angiogenesis: vascular endothelial
      growth factor (VEGF), heparin affin regulatory peptide (HARP) and inducible
      nitric oxide synthase (iNOS). MATERIALS AND METHODS: An area of 1 cm2 of the CAM,
      restricted by a plastic ring was irradiated at room temperature. The expression
      of the genes was studied using RT-PCR and the amounts of the mRNAs were
      quantified using image analysis of the corresponding agarose gels of the RT-PCR
      products. RESULTS: VEGF mRNA was decreased 6 h after irradiation. However, at
      later time points, VEGF expression was significantly increased compared with the
      nonirradiated tissue. Similarly, X-rays down-regulated both HARP and iNOS
      expression 6 h after irradiation and the effect was reversed at later time
      points, similarly to the effect of X-rays on VEGF. CONCLUSION: These data support
      the notion that X-rays increase the expression of genes that favor angiogenesis.

PMID- 15517901
TI  - Ex vivo responsiveness of head and neck squamous cell carcinoma to glufosfamide,
      a novel alkylating agent.
AB  - BACKGROUND: Glufosfamide is a novel alkylating agent in which the active
      metabolite of isophosphoramide mustard is glycosidically linked to beta-D
      glucose. Targeting the elevated glucose uptake of tumor cells expressing the
      SAAT1 glucose transporter, glufosfamide represents an attractive new drug for
      cancer chemotherapy. The present study investigates the ex vivo responsiveness of
      Head and Neck Squamous Cell Carcinoma (HNSCC) specimens to glufosfamide. PATIENTS
      AND METHODS: Twenty-one unselected HNSCC specimens were investigated using a
      novel ex vivo colony formation assay to determine the epithelial drug response.
      The individual responsiveness to glufosfamide and to cis-platinum was determined.
      RESULTS: Five out of 21 evaluable HNSCC specimens were sensitive to glufosfamide.
      There was a tendency for glufosfamide sensitivity in platinum-resistant specimens
      and vice versa. CONCLUSION: The effectiveness of glufosfamide observed in the
      present ex vivo study suggests at least an equipotentiality of glufosfamide in
      comparison to cis-platinum. The potential clinical usefulness of glufosfamide in
      HNSCC warrants further evaluation.

PMID- 15517902
TI  - IGF-I in mammary tumorigenesis and diabetes.
AB  - Insulin growth factors (IGFs) are important mediators of growth, development,
      differentiation and survival of normal and transformed cells. Many complex and
      diverse types of molecules modulate these actions. In vitro and in vivo
      experiments have demonstrated that this system (IGF) is strongly related to the
      establishment of the transformed phenotype. Recent studies confirmed the
      association between serum levels of IGF-I and diverse malignant diseases while
      some relationships with other pathologies since Diabetes Mellitus have been
      described. Currently, IGFs are considered important targets for the study of new
      therapeutic drugs and strategies for cancer treatment. In this review, we have
      summarized the latest data specially linking IGF-I and its receptor with breast
      cancer.

PMID- 15517903
TI  - Novel recurrent structural chromosomal aberrations in primary bladder cancer.
AB  - BACKGROUND: Bladder cancer is a heterogeneous genetic disease and, to date, no
      specific cytogenetic abnormality has been established. The detection of recurrent
      genetic changes with common breakpoints is of special interest, facilitating the
      identification of genes implicated in carcinogenesis. The aim of this study was
      to investigate recurrent structural chromosomal aberrations with common
      breakpoints and to correlate them with the histological stage of tumors.
      MATERIALS AND METHODS: Fifteen patients with transitional cell carcinoma of the
      bladder were cytogenetically studied by direct culture of primary tumor cells and
      G-banding technique. RESULTS: Most of the cases studied exhibited very complex
      karyotypes. Recurrent structural aberrations were observed involving, according
      to frequency, chromosomal regions 11p15, 3p12, 14q32, 19q13 and 6q23.
      Isochromosomes i(8q), i(17q) and i(6p) were also observed. CONCLUSION:
      Conventional cytogenetics continues to be valuable in cancer study, detecting
      common chromosomal breakpoints. Of interest was the detection of novel recurrent
      structural chromosomal aberrations including involvement of 11p15, 14q32 and
      19q13, while a correlation of recurrent abnormalities observed with tumor stage
      was also evaluated.

PMID- 15517904
TI  - Applicability of the 2-nitroimidazole-sodium borocaptate-10B conjugate, TX-2060,
      as a 10B-carrier in boron neutron capture therapy.
AB  - BACKGROUND: It is difficult to deliver a therapeutic amount of 10B from
      conventional 10B-carriers for boron neutron capture therapy (BNCT) throughout the
      target tumors, especially into the intratumor hypoxic cells which have low uptake
      capacities. We evaluated the usefulness of 5 new 10B-compounds (TX-2041, TX-2042,
      TX-2058, TX-2059 and TX-2060) as 10B-carriers in BNCT. They are 2-nitroimidazole
      sodium borocaptate-10B (BSH) conjugates, that is, hybrid compounds that have both
      a hypoxic tumor cell sensitizing unit under gamma-ray irradiation, 2
      nitroimidazoles and a thermal neutron-sensitizing unit, BSH. MATERIALS AND
      METHODS: The 5 new compounds were administered to SCC VII tumor-bearing mice
      intraperitoneally. As a control, BSH was also administered in the same manner.
      Then, the 10B concentrations in the tumors and normal tissues were measured by
      gamma-ray spectrometry. Based on the data of the pharmacokinetics analyses, TX
      2060 was chosen for a subsequent tumor-irradiation study. SCC VII tumor-bearing
      mice were continuously given 5-bromo-2'-deoxyuridine (BrdU) to label all
      proliferating (P) cells in the tumors, then treated with TX-2060 or BSH in the
      same manner as in the pharmacokinetics analyses. To obtain similar intratumor 10B
      concentrations during radiation exposure, irradiation with thermal neutrons or
      gamma-rays was started from 60 min after administration of the 10B-carrier. Right
      after irradiation, the tumors were excised, minced and trypsinized. The tumor
      cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis
      blocker), and the micronucleus (MN) frequency in cells without BrdU-labelling (=
      quiescent (Q) cells) was determined using immunofluorescence staining for BrdU.
      Meanwhile, the MN frequency in total (P + Q) tumor cells was determined from the
      tumors that were not pretreated with BrdU. The clonogenic cell survival was also
      determined in mice given no BrdU. RESULTS: 10B distribution analyses in tumors,
      muscles, blood and liver indicated that TX-2060 has the most favorable
      characteristics for concentrating a sufficient amount of 10B in tumors and
      maintaining a high enough 10B concentration during irradiation. In addition, TX
      2060 had a significantly stronger radio-sensitization effect with reactor thermal
      neutron beams than BSH on both total and Q cells in solid tumors. Further, TX
      2060 clearly exhibited a radio-sensitization effect with gamma-rays, not only on
      total cells but also on Q and hypoxic tumor cells, which was not achieved by BSH.
      CONCLUSION: 10B-carrier, with a gamma-ray-sensitizing effect on tumor cells as
      well as the potential to keep 10B in tumors and sensitize tumor cells more
      markedly than conventional 10B-carriers, such as TX-2060, is a promising
      candidate for use in BNCT.

PMID- 15517905
TI  - Does the sequence of gemcitabine and vinorelbine affect their efficacy in non
      small cell lung cancer in vitro?
AB  - BACKGROUND: We have recently completed a large phase III trial in advanced non
      small cell lung cancer (NSCLC) in the elderly which showed that the combination
      of gemcitabine (GEM) plus vinorelbine (VNR), with GEM administered first, did not
      improve any outcome as compared with each single drug. MATERIALS AND METHODS: The
      anti-tumor efficacy of different sequences of administration of GEM and VNR was
      investigated in a small panel of NSCLC cell lines, by using an in vitro cytotoxic
      assay and isobologram analysis. RESULTS: Treatment of lung cancer cells with GEM
      followed by VNR resulted in moderate synergism in one cell line (A549), and in
      antagonism in two cell lines (H838 and H1355). However, treatment of NSCLC cells
      with VNR followed by GEM resulted in antagonism in all cell lines. CONCLUSION:
      The results of this study show that the GEM/VNR combination is not superior to
      both single agents against NSCLC cells, independently of the schedule of
      administration of the drugs.

PMID- 15517906
TI  - Down-regulation of cyclin E expression by caffeine promotes cancer cell entry
      into the S-phase of the cell cycle.
AB  - Expression of cyclin E is believed to be a critical factor promoting cell entry
      into the S-phase and cell proliferation. Indeed, normal proliferating cells and
      most tumor cell lines are characterized by the existence of a minimal cyclin E
      threshold level in the G1-phase, and only those cells expressing cyclin E over
      this threshold enter into the S-phase of the cell cycle. However, through
      studying clinical tumor tissue specimens, we recently observed that some cancer
      cells can enter into the S-phase with minimal levels of cyclin E expression. In
      an effort to establish an in vitro cell model system for studying the mechanisms
      underlying this phenomenon, we treated MOLT-4 lymphocyte leukemia cells with 50
      mM caffeine and found that the levels of cyclin E expression were decreased
      markedly in these cells following 2 to 4-h exposure to caffeine. Quite
      unexpectedly, we observed that the percentage of the cells progressing through
      the S-phase increased despite the reduced levels of cyclin E, as analyzed for the
      cellular DNA contents, expression of nuclear-bound PCNA, immunolabelling with Ki
      67 antibody and incorporation of BrdU. In fact, these cells entered into the S
      phase with a level of cyclin E well below the threshold level for untreated
      cells, thus suggesting that lower levels of cyclin E expression are associated
      with cell proliferation under certain circumstances. We speculate that caffeine
      may enhance MOLT-4 cell entrance into the S-phase through activation of Cdc25,
      which in turn activates cyclin-dependent protein kinases (CDKs) including CDK2
      and drives the cell cycle progression; while degradation of cyclin E by the
      ubiquitin/proteasome pathway may account for the decreased levels of cyclin E in
      these cells. Our findings from both the MOLT-4 cell line and patients' cancer
      tissues may help decipher the mystery of the deregulation of cell cycle
      progression and carcinogenesis in some malignant tumors.

PMID- 15517907
TI  - Gene therapy of prostate xenograft tumors with a p75NTR lipoplex.
AB  - The p75neurotrophin receptor (p75NTR) has been characterized as a tumor
      suppressor in human prostate cancer. Ectopic re-expression of this cell surface
      receptor protein in prostate cancer cell lines has been shown to increase the
      frequency of apoptosis and concurrently reduce the rate of cellular
      proliferation. Since it is difficult to maintain a therapeutic level of this
      membrane receptor protein by systemic administration in the blood, we utilized an
      alternative gene therapy strategy based upon intra-tumoral injection into
      xenografts of PC-3 prostate tumor cells of a lipoplex containing the p75NTR gene.
      Administration of the p75NTR gene into subcutaneous PC-3 xenografts suppressed in
      a dose-dependent manner the growth of tumors. Within the gene therapy-treated
      tumors, re-expression of the p75NTR gene product was associated with increased
      apoptosis and reduced proliferation of tumor cells. These results suggest that
      the p75NTR may be a suitable candidate for gene therapy of prostate cancer cells.

PMID- 15517908
TI  - Penetration into solid tumor tissue of fluorescent latex microspheres: a mimic of
      liposome particles.
AB  - BACKGROUND: Using liposomes as a vehicle to transport anticancer drugs to cancer
      cells, to increase their effectiveness and decrease their toxicity, has been
      studied for many years. However, due to technical difficulties, the path of
      penetration for liposome particles into solid tumor tissue is still not clear.
      MATERIALS AND METHODS: In this report, rhodamine-labeled fluorescent latex
      microspheres were used as a model of liposome particles, combined with
      fluorescent staining of blood vessel CD31 and tumor cell nuclei. The penetration
      of microspheres from blood vessels in L1210JF solid tumors of mice was observed.
      After fluorescent latex microspheres were injected into tail vein, tumor tissue
      samples were collected at various times and cryosections were then made for
      fluorescent staining. RESULTS: Under fluorescence microscopy, the red fluorescent
      latex microspheres, the green fluorescent blood vessels and the blue tumor cells
      in the cancer tissue were seen clearly. The leaking of microspheres out from
      blood vessels was seen directly. CONCLUSION: The results confirmed that the tiny
      particles can only leak out through the holes of the broken blood vessels and
      spread out through the space in between the cells of the solid tumor.

PMID- 15517909
TI  - VGA1155, a novel binding antagonist of VEGF, inhibits angiogenesis in vitro and
      in vivo.
AB  - The process of angiogenesis involves the formation of new blood vessels from
      established vasculature and is essential for progressive tumor growth and
      metastasis. Since vascular endothelial growth factor (VEGF) plays a pivotal role
      in tumor angiogenesis, it is reasonable to expect that antagonizing VEGF binding
      to its receptor may be effective in cancer therapy. Our previous study found that
      a novel low molecular weight compound, VGA1155, inhibited binding between
      radioisotope-labelled VEGF and cells overexpressing its two receptors, Flt-1 and
      KDR/Flk-1, that is, NIH3T3-Flt-1 and NIH3T3-KDR, respectively. In the present
      study, we investigated the anti-angiogenic effects of VGA1155 based on VEGF
      inhibition. VGA1155 inhibited VEGF-induced DNA synthesis of human umbilical vein
      endothelial cells (HUVEC) and human retinal endothelial cells (HREC) in a
      concentration-dependent manner. VGA1155 also inhibited VEGF-induced tube
      formation of HUVEC in vitro and tumor angiogenesis toward B16-BL6 melanoma after
      orthotopic implantation into the skin of the back. On the other hand, VGA 1155
      did not affect the proliferation of human epidermoid carcinoma (KB) cells and
      mouse mammary carcinoma (MM2) cells. It also had no effect on the activity of
      several cytosolic kinases such as p55fyn and p56lck. These findings suggest that
      VGA1155 inhibits endothelial cell growth and angiogenesis by inhibiting VEGF
      function but not non-specific cytotoxicity. VGA1155 thus exhibits promise as an
      antiangiogenic or anti-tumor agent with fewer side-effects.

PMID- 15517910
TI  - Kinetic radical scavenging activity and cytotoxicity of 2-methoxy- and 2-t-butyl
      substituted phenols and their dimers.
AB  - The dimers bis-EUG, bis-MMP, bis-BHA, bis-BMP and bis-DBP were synthesized from
      the monomers 4-allyl-2-methoxyphenol (EUG), 2-methoxy-4-methylphenol (MMP), 2-t
      butyl-4-methoxyphenol (BHA), 2-t-butyl-4-methylphenol (BMP) and 2,4-di-t
      butylphenol (DBP), respectively. The stoichiometric factors (n; number of free
      radicals trapped by one mole of phenolic moiety) of these compounds were
      determined by induction period methods with a kinetic approach in the 2'2
      azobisisobutyronitrile (AIBN) and benzoyl peroxide (BPO) systems at 70 degrees C.
      The n values for bis-EUG, bis-MMP and bis-BHA were approximately two-fold greater
      than those for their monomers in both the AIBN and BPO systems, whereas the n
      values for bis-BMP and bis-DBP were identical to those of their monomers. bis
      EUG, bis-MMP and bis-BHA, containing methoxy groups, were potent antioxidants.
      The n values (1.3-1.6) for EUG and MMP were considerably less than 2, as is
      commonly observed for the stoichiometric factors of phenolic compounds. The
      antiradical efficiencies against DPPH (diphenylpicrylhydrazyl) of the monomers
      and their dimers were also investigated, likewise indicating that bis-EUG, bis
      MMP and bis-BHA were potent antioxidants. DBP and bis-DBP were less effective
      radical scavengers because of the steric factor of their bulky t-butyl groups. On
      the basis of cytotoxic activity against a human submandibular gland carcinoma
      cell line (HSG) and human gingival fibroblasts (HGF), these compounds could be
      classified into a high-activity group (DBP, bis-DBP and bis-BMP, with butylated
      hydroxytoluene (BHT) as a positive control) and a low-activity group (MMP, EUG,
      BHA, BMP, bis-BHA and bis-EUG). The cytotoxicity of EUG and BHA was markedly
      reduced by dimerization, whereas that of MMP was enhanced. The sensitivity index
      (ratio of 50% cytotoxic concentration for HGF cells to that for HSG cells) of
      EUG, MMP, bis-MMP and bis-BHA was approximately 9, 5, 7 and 2, respectively,
      whereas that of the other compounds was approximately 1. Potential mechanisms of
      cytotoxicity were assessed by PM3 semiempirical molecular orbital (MO)
      calculations. Tumor cells were highly sensitive to 2-methoxy-4-alkylphenols such
      as EUG and MMP, possibly due to the formation of cytotoxic quinone methide
      intermediates. In contrast, the high sensitivity index of bis-MMP may be related
      to the production of a highly reactive substance, CH3+, via oxidation. Structure
      activity relationship (SAR ) models using PM3 calculations may be useful to
      predict biological activity during the development of potential anticancer drugs.

PMID- 15517911
TI  - Absence of ras-gene hot-spot mutations in canine fibrosarcomas and melanomas.
AB  - Point mutations within ras proto-oncogenes, particularly within the mutational
      hot-spot codons 12, 13 and 61, are frequently detected in human malignancies and
      in different types of experimentally-induced tumours in animals. So far little is
      known about ras mutations in naturally occurring canine fibrosarcomas or K-ras
      mutations in canine melanomas. To elucidate whether ras mutations exist in these
      naturally occurring tumours in dogs, in the present study we screened 13 canine
      fibrosarcomas, 2 feline fibrosarcomas and 11 canine melanomas for point
      mutations, particularly within the mutational hot-spots, making this the first
      study to investigate a large number of canine fibrosarcomas. None of the samples
      showed a K- or N-ras hot spot mutation. Thus, our data strongly suggest that ras
      mutations at the hot-spot loci are very rare and do not play a major role in the
      pathogenesis of the spontaneously occurring canine tumours investigated.

PMID- 15517912
TI  - The role of insulin-like growth factor 1 and insulin-like growth factor binding
      protein 3 in human esophageal cancer.
AB  - BACKGROUND: Insulin-like growth factors (1GF-1) and insulin-like growth factor
      binding protein-3 (IGFBP-3) play important roles in cell growth and
      differentiation. The aim of this work was to investigate the roles of IGF-1 and
      IGFBP-3 in esophageal cancer. MATERIALS AND METHODS: We examined the circulating
      IGF-1 and IGFBP-3 concentration in 18 healthy controls and 66 esophageal cancer
      patients by ELISA and a ligand capture immunoassay. Immunohistochemistry for IGF
      1 was performed on surgical specimens obtained from 93 patients with esophageal
      cancer. RESULTS: The serum IGF-1 and IGFBP-3 levels were significantly elevated
      in patients compared with healthy subjects and there was a positive correlation
      between IGF-1 and IGFBP-3. There was a significant correlation between IGF-1
      level and depth of invasion and pathological stage. Poor prognosis was
      significantly correlated with increasing IGF-1 levels. The survival rates of high
      IGF-1 expression immunohistochemical study patients were poorer than those of low
      expression patients. CONCLUSION: Elevated serum IGF-1 levels may be an important
      predictor of risk for esophageal cancer. IGF-1 related to the progression of
      esophageal cancer may depend on an autocrine function of IGF-1.

PMID- 15517913
TI  - Doxorubicin activates hepatitis B virus (HBV) replication in HBV-harboring
      hepatoblastoma cells. A possible novel mechanism of HBV reactivation in HBV
      carriers receiving systemic chemotherapy.
AB  - BACKGROUND: Reactivation of HBV replication is a clinically significant
      complication in HBV(+) patients receiving chemotherapy. We recently found that
      nearly half of the HBV reactivation in lymphoma patients occurred within 2 weeks
      of the first dose of chemotherapy. We hypothesized that mechanisms other than
      immunosuppression, such as direct stimulation of HBV replication by anticancer
      drugs, might be involved in this type of HBV reactivation. MATERIALS AND METHODS:
      2.2.15 cells, which secrete HBV particles constitutively, were used in the
      experiments. Real-time quantitative polymerase chain reaction was used to
      quantitate HBV DNA, and microparticle enzyme immunoassay to measure HBV surface
      antigen (HBsAg). RESULTS: HBV DNA secretion in culture medium was dose-
      dependently increased by doxorubicin, one of the most commonly used anticancer
      drugs for lmphoma. One-hour exposure of cells to 1 microM doxorubicin induced a
      15.4+/-5.9-fold and a 3.05+/-0.09-fold increase of HBV DNA and HBsAg on the 4th
      culture day, respectively. Lamivudine suppressed the doxorubicin-induced increase
      of HBV DNA. CONCLUSION: Our data suggest that cytotoxic agents may stimulate the
      replication of HBVand thereby contribute to the reactivation of HBV during
      systemic chemotherapy. Importantly, this adverse effect of cytotoxic agents may
      be preventable by co-administration of lamivudine.

PMID- 15517914
TI  - E2F-1 transcription factor immunoexpression is inversely associated with tumor
      growth in colon adenocarcinomas.
AB  - E2F-1 is an intriguing transcription factor that accumulates the integrated
      signal of the G1-S transition regulators. Its role in cell fate, as depicted from
      in vivo models and a few studies on human tissues, is a matter of debate, since
      it confers a tissue-specific oncogenic or tumor suppressor behavior. In the
      present work, in an attempt to shed light on the role of E2F-1 in colon cancer,
      we examined E2F-1 expression in a series of 45 colon carcinomas and we further
      correlated it with tumor kinetics. E2F-1 expression and proliferation were
      evaluated by immunohistochemistry as the percentage of E2F-1 (E2F-1 index: EI)
      and Ki-67 (Proliferation index: PI)-positive cells, respectively; whereas
      apoptosis was estimated as the percentage of positive, by TUNEL assay, cells
      (Apoptotic index: AI). The relationship between E2F-1 expression and tumor
      kinetics was assessed by microscopical evaluation in semi-serial tissue sections
      and statistical analysis. Our results demonstrated that E2F-1 expression was
      inversely correlated with tumor growth (GI=PI/AI) (p=0.002). Specifically, the
      histological observations showed that E2F-1 was expressed in lesions with high
      apoptotic incidence and low proliferation. These results also supported the
      statistical findings showing that EI was inversely correlated with PI (p < 0.001)
      and positively associated with AI (p = 0.013). In conclusion, we suggest a tumor
      suppressive behavior of E2F-1 in colon carcinomas.

PMID- 15517915
TI  - Efficacy of garbanzo and soybean flour in suppression of aberrant crypt foci in
      the colons of CF-1 mice.
AB  - BACKGROUND: Epidemiological studies have reported a low incidence of colon cancer
      in countries with high legume consumption. Moreover, experimental studies have
      found that legumes, such as soybeans and pinto beans, have anticancer properties.
      While garbanzo beans are a rich source of various phytochemicals, they have not
      been well studied. In the present study, the azoxymethane (AOM)-induced aberrant
      crypt foci (ACF) in CF-1 mice was utilized as a model to assess and compare the
      effects of garbanzo flour to that of soy flour. MATERIALS AND METHODS: Twenty, 5
      week-old CF-1 mice were divided into four groups of 5 animals each: 10% garbanzo,
      10% soy, 10% mixed (soy and garbanzo flours), and control (rodent chow). Animals
      received subcutaneous injections of AOM (10-mg/kg B. W.) once a week for two
      weeks to induce ACF. At week ten, the animals were sacrificed and the colons were
      scored. RESULTS: There was a 64% (p <0.001) suppression of ACF for animals fed
      the garbanzo flour, versus an inhibition of 58 and 55% (p<0.001) for the soy and
      mixed flour groups, respectively. DISCUSSION: These results demonstrate that
      garbanzo beans possess bioactive compounds capable of inhibiting the formation of
      pre-cancerous lesions in mice and suggest that, like soybeans, their consumption
      contributes to a reduction in colon cancer incidence.

PMID- 15517916
TI  - Expression of glucose transporter 1 (Glut-1) in cell lines and clinical specimens
      from human prostate adenocarcinoma.
AB  - BACKGROUND: Increased uptake and metabolism of glucose is a characteristic of
      malignant transformation. Overexpression of glucose transporters, especially Glut
      1, is a common event in human malignancies. To date, little is known about the
      role of Glut-1 in human prostate cancer (PC). The aim of this study was to
      investigate the expression of Glut-1 both in PC cell lines and clinical specimens
      of primary PC. MATERIALS AND METHODS: The PC cell lines DU145, PC3 and LNCaP were
      assessed for Glut-1 mRNA expression by Northern blot analysis. In a total of 45
      primary PC specimens, radioactive (35S) in situ hybridizations (RISH) for Glut-1
      mRNA expression were performed on frozen sections. Quantification of Glut-1
      expression was obtained by use of an image analysis system. RESULTS: Glut-1
      expression was detected in all 3 cell lines. Expression in the more poorly
      differentiated cell lines DU145 and PC3 was even higher than in the hormone
      responsive LNCaP cell line. In situ hybridizations in primary PC revealed Glut-1
      expression just above the detection limit in well-differentiated tumors.
      Significantly increased Glut-1 expression was detected in moderately- to poorly
      differentiated PC. CONCLUSION: Glut-1 is expressed in PC cell lines and primary
      PC. The level of expression increases with advancing grade of malignancy. These
      findings support a role for Glut-1 in PC proliferation.

PMID- 15517917
TI  - Protective effects of EGCG on salivary gland cells treated with gamma-radiation
      or cis-platinum(II)diammine dichloride.
AB  - Dysfunction of salivary glands is often associated with aging and cancer therapy.
      Green tea polyphenols were previously found to protect normal epithelial cells
      from reactive oxygen species, and to induce apoptosis in tumor cells. The current
      study investigated whether -(-) epigallocatechin-3-gallate (EGCG), the major
      green tea polyphenol, protects normal salivary gland cells from the effects of
      gamma-irradiation and the chemotherapy drug cis-platinum(II)diammine dichloride
      (CDDP). Human immortalized salivary acinar and ductal cells, and oral squamous
      cell carcinoma cells were irradiated with gamma-rays or treated with CDDP, with
      or without pretreatment with EGCG, followed by MTT and BrdU incorporation assays.
      The results demonstrated that EGCG protected the normal salivary gland cells from
      chemical or irradiation-induced damage. However, protection of oral cancer cells
      by EGCG was also observed if EGCG was at physiologically achievable salivary
      concentrations but not at higher concentrations, suggesting that the combination
      of green tea consumption with cancer therapy requires further evaluation.

PMID- 15517918
TI  - Gene therapy in colon cancer cells with a fiber-modified adenovector expressing
      the TRAIL gene driven by the hTERT promoter.
AB  - BACKGROUND: Repeated administration of adenoviral vectors can lead to cell
      resistance, probably because of the initial coxsackie-adenovirus receptor (CAR).
      Modified adenoviral vectors containing an Arg-Gly-Asp (RGD) sequence can overcome
      resistance. We constructed an adenoviral vector with RGD-modified fibers,
      expressing the TRAIL gene from the human telomerase reverse transcriptase (hTERT)
      promoter (designated Ad/TRAIL-F/RGD), and tested its antitumor activity in 5
      colon carcinoma cell lines. MATERIALS AND METHODS: Colon cancer cells were
      infected with Ad/CMV-GFP (vector control), Ad/gTRAIL (positive control) and
      Ad/TRAIL-FIRGD. PBS was used as a control. Cell viability was determined by
      proliferation assay. Cell-cycle analysis and quantification of Caspase-8 and
      TRAIL were used to identify apoptosis. RESULTS: Treatment with Ad/TRAIL-F/RGD
      resulted in significantly less cell viability, increased Caspase-8 and TRAIL
      activity, and a greater apoptotic fraction than treatment with PBS or Ad/CMV-GFP.
      CONCLUSION: The adenoviral vector Ad/TRAIL-F/RGD could become a potent
      therapeutic agent for the treatment of colon carcinoma.

PMID- 15517919
TI  - Cluster analysis of apoptosis-associated bcl2 family proteins in diffuse large B
      cell lymphomas. Relations with the apoptotic index, the proliferation profile and
      the B-cell differentiation immunophenotypes.
AB  - BACKGROUND: There is evidence that apoptotic mechanisms mediated by bcl2 family
      proteins are involved in the pathogenesis of diffuse large B-cell lymphomas
      (DLBCL). In order to gain further insight into the apoptosis profile of DLBCL, 79
      cases were investigated to determine whether distinct clusters of the combined
      expression levels of bcl2 family proteins can be identified in these lymphomas.
      MATERIALS AND METHODS: The combined immunohistochemical expression levels of the
      proteins bax, bak, bad, bid, bcl2 and bcl-xl were evaluated by cluster and
      discriminant analysis. The produced clusters were analyzed in relation to the
      apoptotic index, the proliferation profile and the B-cell differentiation
      immunophenotypes. RESULTS: Cluster analysis produced: a) a low expression (69/79
      cases) and a high expression pro-apoptotic cluster (10/79 cases) for the combined
      expression levels of the pro-apoptotic proteins bax, bak, bad and bid and b) a
      low expression (37/76 cases) and a high expression antiapoptotic cluster (39/76
      cases) for the combined expression levels of anti-apoptotic proteins bcl2 and bcl
      xl. The decreasing order of discriminant power for the percentages of tumor cells
      expressing pro-apoptotic and anti-apoptotic proteins was % bax + cells> % bak+
      cells> % bid+ cells> % bad+ cells and % bcl2+ cells> % bcl-xl+ cells,
      respectively. The high expression pro-apoptotic cluster was significantly
      associated with higher mean values of Ki67 (p=0.047) and cyclin A (p=0.033)
      expression. The high expression pro-apoptotic cluster was significantly
      associated with the germinal center B-cell bc16/CD10/MUM1/CD138 differentiation
      immunophenotype (p=0.043). CONCLUSION: This study identified distinct clusters of
      DLBCL with respect to the combined expression levels of the apoptosis-associated
      bcl2 family proteins. These findings, taken together with our previous
      observations that distinct clusters with respect to the apoptotic index and the
      proliferation profile are identified in DLBCL, indicate that subgroups with
      distinct cellular kinetic properties can be defined in these lymphomas. The
      cluster analysis approach might be useful for the identification of subgroups of
      DLBCL with different clinical behavior since increased proliferation and
      apoptosis were reported to be associated with aggressive tumor behavior in these
      lymphomas.

PMID- 15517920
TI  - Monoterpenes enhanced the sensitivity of head and neck cancer cells to radiation
      treatment in vitro.
AB  - BACKGROUND: Perillyl alcohol (POH) elicited anticarcinogenic effects in a number
      of cancer models and pharmacokinetic studies in humans revealed that PA is the
      major circulating metabolite following POH administration. MATERIALS AND METHODS:
      Effects of PA or POH alone, or in combination with radiation, on human head and
      neck squamous cell carcinoma cell lines (HNSCC), were investigated using
      cytotoxicity and flow cytometry assays. HNSCC cells were pretreated with 1.0 mM
      PA or 0.5 mM POH for 72 h before exposure to 1 or 2Gy dose of radiation. RESULTS:
      Pretreatment of the cells with 1.0 mM PA or 0.5 mM POH prior to irradiation,
      caused the following growth inhibition: HTB-43 (50% or 71%), SCC-25 (55% or 68%),
      and BroTo (18% or 53%). PA and POH induced cell-cycle arrest and apoptosis.
      CONCLUSION: PA and POH have potential for use as radiosensitizers in chemo
      radiation therapy of head and neck cancers and should be further studied.

PMID- 15517921
TI  - [Pharmacotherapy of chronic heart failure in clinical practice].
AB  - Chronic heart failure affects between 1-5% of the population and rise steeply
      with age. Most patients with chronic heart failure should be routinely managed
      with a combination of 4 types of drugs: a diuretic, an angiotensin converting
      enzyme inhibitors (ACE-I), beta-blocker and usually digitalis. Diuretics are
      essential for symptomatic treatment when fluid overload is present, and should
      always be administrated in combination with ACE-I if possible. ACE-I improves
      survival and symptoms and reduces hospitalization in patients with moderate to
      severe ventricular systolic dysfunction, and in the absence of fluid retention
      should be given first. Angiotensin II receptor antagonist could be considered in
      patients who not tolerate ACE-I. beta-blocking agents are recommended for
      treatment of patients with stable, mild, moderate and severe heart failure unless
      there is a contraindication. Bisoprolol, metoprolol and carvedilol have been
      associated with reduction in total mortality, cardiovascular mortality and sudden
      death. Cardiac glycosides are indicated in atrial fibrillation and any degree of
      symptomatic heart failure in order slow ventricular rate. Indications for
      antiarrhythmic drug therapy include atrial fibrillation, non-sustained or
      sustained ventricular tachycardia. Oral anticoagulation reduces the risk of
      stroke in patients with atrial fibrillation, and there is a lack of evidence to
      support the use of antithrombotic therapy in patients in sinus rhythm.

PMID- 15517922
TI  - [Comparison of usefulness of dobutamine-atropine and dobutamine-adenosine stress
      echocardiography in detection of coronary artery disease].
AB  - Stress echocardiography is valuable, non-invasive method useful for detection of
      coronary artery disease. In stress echocardiography myocardial ischemia is most
      commonly induced by exercise or pharmacological agents like dobutamine,
      dypiridamole, arbutamine or adenosine. The aim of the study was to compare
      usefulness of dobutamine-atropine stress echocardiography (DATR) with dobutamine
      adenosine stress echocardiography (DADE) in detection of coronary artery disease.
      Studies were carried out in 23 patients, 11 women and 12 men, with suspected
      coronary artery disease. Both DATR and DADE were performed in all patients. In
      DATR left ventricular segmental contractility was estimating during intravenous
      infusion of dobutamine in increasing doses from 5 to 40 microg/kg/min and after
      intravenous administration of 1 mg of atropine. In DADE regional left ventricular
      systolic function was analyzed during intravenous infusion of dobutamine in
      increasing doses from 5 to 40 microg/kg/min and adenosine in dose of 0.14
      mg/kg/min. The sensitivity of DATR in detection of coronary artery disease was
      87% and specificity was 85%, whereas DADE 87% and 100% respectively. The
      sensitivity of DATR and DADE in subgroups of patients with one-vessel and
      multivessel disease was equal: 83% and 90% respectively. There were no
      significant differences between DADE and DATR in respect of sensitivity and
      specificity in detection of coronary artery disease. The results of this study
      suggest that dobutamine-adenosine stress echocardiography is highly sensitive and
      specific diagnostic test for detection both one-vessel and multivessel coronary
      artery disease. Moreover, there is no statistically important difference between
      dobutamine-adenosine stress echocardiography and dobutamine-atropine
      echocardiography in respect of sensitivity and specificity in detection of
      coronary artery disease.

PMID- 15517923
TI  - [Predictors of one-year mortality in diabetic and nondiabetic patients with
      ischemic stroke].
AB  - The study was designed to compare the independent predictors of one-year
      mortality after ischemic stroke in patients with and without diabetes. We studied
      667 patients with ischemic stroke, including 166 diabetic patients and 501
      patients without diabetes. The diagnosis of ischemic stroke was confirmed in each
      case by computed tomography (CT) of the head. We collected data on patients' sex,
      age, and on the presence of major risk factors for stroke. The neurological
      deficit, including the disorders of consciousness, was assessed by Scandinavian
      Stroke Scale on admission. The body temperature was measured on admission and
      then every four hours during the first day of hospitalization. The outcome was
      measured by 30-day and one-year all cause mortality. The neurological deficit and
      the percentage of patients with large ischemic lesions in CT scanning were
      similar in patients with and without diabetes. Lacunar infarcts were more
      frequently seen in diabetics (30.1 vs 22.5%; p < 0.05). Diabetic and non-diabetic
      patients had similar 30-day and one-year mortality (16.3 vs. 17.6% and 41.0 vs.
      35.1%, respectively; p = ns, chi2 test). One-year mortality among patients with
      non-lacunar infarcts was greater in diabetics (51.7%) than in non-diabetics
      (35.3%; p < 0.01). The multinomial logistic regression analysis revealed that
      older age and greater neurological deficit were independent predictors of death
      within one year after stroke in diabetic patients, while older age, greater
      neurological deficit and increased body temperature during the first day of
      hospitalization independently predicted one-year mortality in non-diabetic
      patients.

PMID- 15517924
TI  - [Passive smoking and patterns of 24-hour ambulatory blood pressure in healthy
      children].
AB  - The aim of this study was to compare patterns of 24-hour ambulatory blood
      pressure between passive-smoking and non-smoking children. Subjects were 100
      healthy children divided in 2 groups: passive smokers (72 children) and non
      smokers (28 children). Children underwent 24-hour ambulatory blood pressure
      monitoring (ABPM). On the basis of ABPM results following daytime and night-time
      parameters were calculated for systolic blood pressure (SBP) and diastolic blood
      pressure (DBP): mean blood pressure (BP) value, BP load, BP variability
      magnitude, 24-hour blood pressure profile. The results were compared between
      passive smokers and non-smokers with t-Student test. Results with p < 0.05 were
      considered statistically significant. Smokers did not differ from non-smokers in
      mean daytime and night-time BP values. Daytime BP load, BP variability and 24
      hour SBP profile were statistically higher in passive smokers, while night-time
      values of these parameters and DBP profile did not differ significantly. ABPM may
      be useful in detecting differences in BP characteristics of passive smoking and
      non-smoking children. Higher BP load and BP variability in smoking children may
      be early manifestations of BP regulation disorder, which might be helpful in
      early screening. Passive smoking may be a risk factor of hypertension.

PMID- 15517925
TI  - [Are age and educational level the determinants of hormonal parameters considered
      as indices of andropause?].
AB  - The involutionary processes in gonadal and adrenal glands are significant for
      male aging. The dynamics of hormonal changes in aging men seems to be
      individually differentiated and vary in distinct populations. Currently there are
      no data on social differences in hormonal parameters in men. The study was
      carried out in order to evaluate the age-related changes of hormonal parameters
      considered as indices of andropause and analyze the social gradients in these
      variables in healthy Polish men. Material comprised the data of 414 healthy men,
      inhabitants of Wroclaw, aged 32-79, examined in 2000 in DOLMED (Wroclaw, Lower
      Silesia). Serum levels of the following hormones were assessed using
      radioimmunological assays: free testosterone (FT), total testosterone (TT),
      estradiol (E2), dehydroepiandrosterone sulphate (DHEAS), luteinizing hormone
      (LH), sex hormone binding globulin (SHBG) and insulin-like growth factor 1 (IGF
      1). The following indices were calculated: FAI (Free Androgen Index), TT/E2 and
      TT/LH. Among Polish men there were negative correlations between age and serum
      levels of FT, DHEAS, IGF-1, E2, and between age and FAI, TT/LH. The correlation
      between the DHEAS level and age was the strongest among all relationships here.
      The male aging was accompanied by the serum reduction, during 5 years: FT level
      of 4.8%, DHEAS--8.6% and IGF-1--5.0%. The reduction in serum DHEAS and IGF-1
      levels reached 77.3% and 44.9% (respectively) between men aged 32-34 and the
      oldest subjects aged 75-79. The decrease in serum FT level between men aged 32-34
      and those aged 70-74 was 38.2%. The relationships between age and E2 level and
      between age and TT/LH were not strong (respectively, beta = -0.10, p < 0.05 and
      beta = -0. 17, p < 0.001). The male aging was also accompanied by the increase in
      serum SHBG (11.7%/5 years) and LH levels (13.5%/5 years). Among male there were
      no age-related changes in the serum TT level and TT/E2. The results of a two-way
      ANOVA revealed that education significantly differentiated serum IGF-1 levels
      (independently on age). The highest IGF-1 levels were observed in men who had
      graduated from university, the lowest--in those who had finished the trade school
      at the very most. In contrast, there were no social differences in other analysed
      hormonal parameters.

PMID- 15517926
TI  - [The organic disorders in the course of Lyme disease].
AB  - In the last decade the number of patients with Lyme disease has been continuously
      growing worldwide including Poland. Psychiatric examinations with the help of
      psychometric tests were performed in the group of 77 patients with arthritis, in
      20 with neuroborreliosis and 26 with erythema migrans. First evaluations started
      before antibiotic therapy, second 5-6 months after the treatment, third one year
      since the first assessment. Mental state examinations and psychometric testing
      revealed in majority of the patients, mainly in those suffered from
      neuroborreliosis and erythrema migrans evidence of various psychiatric
      symptomatology. The range of psychiatric presentations included: mild cognitive
      deficits, organic mood disorders, mild dementias, depressive and anxiety episodes
      with non organic etiology.

PMID- 15517927
TI  - [Erythrocyte concentrations of adenosine triphosphate (ATP) and magnesium, before
      and after conservative therapy of lower extremities atherosclerosis].
AB  - 37 patients with atherosclerosis of lower extremities and the mean claudication
      distance of 300-500 m (Fontaine 11 degrees) were subjected to pharmacotherapy
      with pentoxyfilline 600 mg twice daily, and walking exercise tests on a
      treadmill. The concentrations of ATP and magnesium ions in erythrocytes were
      assessed in the patients in resting condition, and after standardized walking
      exercise tests, 6 and 12 weeks since the beginning of therapy. Applied treatment
      proved beneficial in protecting the patients against depletion of ATP in their
      erythrocytes. Hypomagnesemia and accompanying lowered concentrations of ATP were
      observed in 1/3 of the cases. As the deficiency of ATP can cause functional
      changes and structural alterations in the erythrocytes and deterioration of the
      clinical condition of these patients supplementing magnesium ions in these cases
      seems justified.

PMID- 15517928
TI  - [Description of mood disorder in patients with epilepsy].
AB  - Prevalence of depression among the people with epilepsy is between 40 and 75%,
      which is higher than in population and among the patients with other chronic
      illness. Higher percentage of suicides and hospitalizations due to affective
      disorders make the diagnosis and evaluation of risk factors very important for
      further treatment. The following study has been performed on the group of one
      hundred patients with epilepsy lasting more than 5 years, aged 16-55, who were
      hospitalized or consulted in 2001 year. Depression was diagnosed on the basis of
      ICD-10 diagnostic scheme using Beck, Hamilton and Montgomery-Asberg Depression
      Scales. Patients were divided into three groups (with depression, dysthymia and
      controls). For statistical analysis chi2 (Fisher exact test) and Mann-Whitney
      test were used. Comparing to controls, the complex partial seizures or simple
      partial and complex ones were seen more often in patients with depression (p <
      0.003) and in patients with dysthymia comparing to controls ones (p < 0.001). All
      types of epileptic seizures analyzed during one month revealed statistically
      significant differences between the groups (Mann-Whitney test: controls vs
      dysthymic ones p < 0.02; controls vs depression ones p < 0.03). Simple partial
      seizures and (or) complex partial ones and high percentage of complex ones were
      found to be statistically significant risk factors for depression and dysthymia.

PMID- 15517929
TI  - [Serum leptin concentration and some lipid parameters in vegetarian children].
AB  - Leptin, a hormone from adipose tissue, regulates feeding behavior, satiation
      rate, energy expenditure and also plays an important role in maturation and
      reproduction. Recent studies support the concept that several factors such as a
      diet may influence on leptin levels. The aim of this study was to investigate
      serum concentration of leptin and lipids status in prepubertal children aged from
      2 to 10 years with two different nutritional habits: vegetarian (n = 24) and
      omnivorous diet (n = 20). Serum leptin concentration was determined by
      immunoenzymeassay (ELISA). Serum lipids (cholesterol, HDL- and LDL-cholesterol,
      triglyceride) were measured by enzymatic and apolipoproteins by
      immunoturbidimetric methods. We noticed that in vegetarian diet there is a high
      rate of fiber (nearly twice as high as in omnivorous diet) and polyunsaturated
      acids (35% as much). In our study vegetarian children had lower total cholesterol
      and cholesterol in fractions HDL and LDL than meat eaters did. Also the
      apolipoproteins levels in vegetarian children were significantly below that of
      nonvegetarians. There is no differences in triglyceride concentration between the
      two groups of children. The mean serum leptin level in vegetarian children was
      significantly lower (3.1 +/- 1.2 ng/mL) as compared with the omnivores (5.6 +/-
      2.1 ng/mL) (p < 0.0001).

PMID- 15517930
TI  - [Therapeutic efficacy of peloid plasters in the treatment of osteoarthritis of
      the peripheral joints and spondylosis].
AB  - The objective of the study was to investigate the efficacy and tolerability of
      the peloid plasters in the group of 20 patients with osteoarthritis of peripheral
      joints (10 patients with gonarthrosis and 10 with omarthrosis) and 20 patients
      with spondylosis. This form of the pelotherapy decreased pain in joints after 10
      days of the treatment. No allergic or other side effects were observed. Peloid
      plasters through the analgesic action improve the comfort of life and reduce the
      use of oral analgesic drugs.

PMID- 15517931
TI  - [The influence of pentoxifylline on the course of experimental peritonitis].
AB  - The influence and relation between pentoxifylline (PTX) dose and time of
      administration and mortality rate of animals with experimental peritonitis (EP)
      were studied. Forty-five rats used in this study. Experimental peritonitis was
      elicited in study animals. All animals were divided onto 3 groups. The sorting
      was made according to drug dose and moment of administration. Group 1--the
      control one--consisted of non-treated animals with EP. Animals from group 2
      received 50 mg of PTX per kg of body weight before cecal ligation and puncture
      (CLP). In group 3 PTX was administered in a dose of 250 mg/kg 8 hrs after CLP.
      The influence of PTX inactivating phosphodiestherase as a cyclooxigenas inhibitor
      on the behavior of C-reactive protein, II-11beta, TNFalph and its soluble sTNF-R
      type I p55 and type II p75 receptors' study animal serum concentrations was
      estimated. The influence of administered drugs on the course of EP was assessed
      by means of animal survival period and CRP serum concentration dynamics
      observation. Thirty-three percent of control group animals survived the
      experiment compared to 53.3% in group 2 and 46.6% in group 3. The study proved
      that PTX administration in animals with EP caused TNFa serum concentration
      decrease, however not changing the overall animal survival rate. On the contrary,
      cycloooxygenase inhibitors decrease arachidonic acid peroxidation product
      cytotoxicity in experimental peritonitis.

PMID- 15517932
TI  - [Peginterferon alpha-2b in patients with chronic hepatitis C].
AB  - 150 adult patients were assigned pegylated interferon alpha-2b (once weekly 1.5
      microg/kg) plus ribavirin (800-1200 mg depending on bodyweight). The treatment
      lasted 52 weeks and was completed by 139 persons (92.7%). Because of adverse
      events the treatment was interrupted in 7 persons, 4 other persons resigned.
      Periodical reduction of pegylated interferon doses was necessary in 19% and the
      reduction of ribavirin in 21% of patients. Six months after the completion of
      treatment HCV-RNA was negative in 82 (59%) patients. Neither hepatitis C virus
      genotype, nor viremia was marked in the study. The negative correlation between
      the degree of fibrosis in the liver tissue and the results of sustained
      virological response was stated. Degree of inflammation at liver tissue, sex, age
      over and less than 40 years did not correlate with the final virological results.
      The recurrence of infection happened at 7% of the treated persons (negative HCV
      RNA directly after the treatment--positive 6 months after the completion). During
      the treatment period, and comparison with the results obtained before its
      implementation, statistically significantly decreased: hemoglobin concentration,
      the number of leukocytes, granulocytes and thrombocytes. They returned to the
      referential values half a year after the completion of treatment. The activity of
      enzymes (AIAT, AspAT, GGTP) was decreasing statistically significantly since the
      first weeks of the treatment till the end and remained significantly lower after
      6 months. In both sexes statistically significant reduction of bodyweight was
      stated, while it increased during the six months after the completion of
      treatment. Adverse events, which mostly were mild and were not the cause of
      interruption of treatment, were numerous and occurred at different frequency, in
      the range from over 50% (flu-like) to 0.7%.

PMID- 15517933
TI  - [Application of the fusafungine in perioperative period in patients after
      tonsillectomy].
AB  - The only treatment method in chronic palatine tonsillitis is the removal of
      tonsils (tonsillectomy). The study aimed at a clinical evaluation of
      postoperative fusafungine use in patients who underwent tonsillectomy. The study
      included 200 patients who underwent tonsillectomy for chronic palatine
      pyotonsillitis in the Otolaryngology Clinic of the Military Institute for the
      Health Services in Warsaw between 2000 and 2002. The patients were divided into
      two groups, each group including 100 patients: group I--patients who underwent
      tonsillectomy, including 67 females and 33 males, aged 16 to 52 (mean age 34.8),
      in whom fusafungine was used; group II--patients who underwent tonsillectomy,
      including 58 females and 42 males, aged 17 to 56 (mean age 36.1), who did not
      receive fusafungine. The subjects were observed during the first 14 days
      following the operation. The treatment was administered from the first day after
      the operation, by spraying 4 doses into the throat, 4 times a day, at 8.00 hrs,
      12.00 hrs, 16.00 hrs and 20.00 hrs. The two groups were then compared in terms
      of: symptoms of sore throat, body temperature, swallowing difficulties, the
      course of healing, appearance of the pharyngeal mucosa, quality of life and
      general affection. Post-tonsillectomy fusafungine use was found to improve the
      patients' quality of life, appeases the sore throat and swallowing difficulties,
      decreases the need for general antibiotic therapy; the above results are
      statistically significant. Fusafungine was not found to influence body
      temperature, the appearance of the pharyngeal mucosa or the healing process.

PMID- 15517934
TI  - [Does long-term erythropoietin therapy influence the prevalence of serum markers
      of hepatitis B and C in haemodialysed uraemic patients?].
AB  - Haemodialysed patients are highly exposed to different virus infections namely
      hepatitis B (HBV) and C (HCV). Recently it was shown, that the use of recombinant
      human erythropoietin (rHuEPO) in haemodialysed patients with chronic renal
      failure (CRF) stimulates not only erythropoesis but also increases--in an
      indirect or direct manner--the humoral and cell--mediated immune defense. The aim
      of the present study was to determine the prevalence of HBV and HCV infection in
      haemodialysed patients with CRF and renal anaemia treated either with rHuEPO or
      with allogenic blood transfusions only. 32 patients with CRF and renal anaemia
      (haematocrit value below 28%) were included in this study at the early stage of
      the dialysis therapy (0 to 6 months from the first haemodialysis session). All
      patients were randomly allocated into two groups. The first one consisted of 15
      haemodialysed patients treated with rHuEPO, the second group composed of 17
      occasionally treated with blood transfusions (No-EPO group). In patients of both
      groups the following parameters were examined before (0) and after 3, 6, 9, 12
      months of monitoring number of units blood transfused, hemoglobin concentration,
      serum levels of ferritin. Before the study (0) and after 6 and 12 months presence
      of antigen HBs (AgHBs), antibodies anti-HBc, anti-HBs, anti-HCV, DNA HBV and RNA
      HCV were examined. Before the study markers of HBV infection (DNA HBV and/or
      AgHBs and/or anti-HBc) were found in 46.7% of patients in EPO group and in 52.9%
      of patients in NO-EPO group respectively (NS). After six months of the study
      markers of HBV infection were present in 60% of patients in EPO group and in
      76.5% of patients in No-EPO group (NS). After 12 months of dialysotherapy HBV
      infection markers were found in 66.7% patients in EPO group and in 76.5% of
      patients in No-EPO group (NS). Significantly higher prevalence of HBV infections
      were found after 6 and 12 months respectively in No-EPO group in comparison to
      the prestudy period (p < 0.05). At the beginning of the study markers of HCV
      infection (RNA HCV and/or anti-HCV) were present in 26.7% of patients in EPO
      group compared to 35.3% of patients in No-EPO group (NS). After 6 months of
      therapy markers of HCV infection were found in 26.7% of patients in EPO group and
      in 64.7% of patients in No-EPO group (p < 0.05). After 12 months of treatment
      markers of HCV infections were present in 40% of patients in EPO group and 76.5%
      of patients in No-EPO group (p < 0.05).ln patients of No-EPO group significantly
      higher prevalence of HCV infection ware found after 6 and 12 months of the follow
      up compared to the prestudy period (p < 0.05 and p < 0.01 respectively).
      CONCLUSIONS: Treatment of renal anaemia with rHuEPO contributes to the
      significant decrease in prevalence of HCV infection. Decrease of prevalence of
      HCV infection in haemodialysed patients with chronic renal failure treated with
      rHuEPO seems to be predominantly a result of the complete cessation of allogenic
      blood transfusion. Blood transfusions seem not to be the main cause of HBV
      transmission in haemodialysed patients.

PMID- 15517935
TI  - [Difficulties in diagnosis of battered child syndrome in infant].
AB  - The diagnosis of battered child syndrome in infants was reached on the basis of
      the risk factors appraisal in social and family history, combined with clinical
      and roentgenographic examinations; the difficulties in establishing the diagnosis
      are presented. Long hospitalisation also revealed that the observed injuries are
      due to child abuse. The interdisciplinary approach is needed when non-accidental
      injuries are considered.

PMID- 15517936
TI  - [The group intoxication by tear-gas].
AB  - The case of group intoxication of 52 pupils by tear CS gas (2
      chlorobenzelidenemaloninitrile) at school is presented. The most often clinical
      signs observed at hospital admitted children, at 13-16 year old were detail
      described. The special attend was given for 4 cases, heavy clinical intoxication
      observed for young girls. The clinical symptoms, action of xenobiotics and
      clinical treatment compare with literature data, were discussed.

PMID- 15517937
TI  - [Bartter syndrome--case report].
AB  - The authors present the case of 4-month-old girl, who was admitted to our
      hospital with hypokalemia, metabolic alkalosis, hyperaldosteronism, hyperreninism
      with normal blood pressure and high urine concentration of PGE2. All the clinical
      and biochemical features have led to the diagnosis of Bartter syndrome. Treatment
      consisted of 15% KCI, spironolacton and indometacin.

PMID- 15517938
TI  - [Medicine hypersensitivity--case report].
AB  - In this paper a case of good tolerance to benzathine benzylpenicillin, but
      benzylpenicillin potassium allergy in subject with history of multidrug
      hypersensitivity was described. The same therapeutic agent is contained in both
      commercial drugs and dosage formulation can cause the unpredictable adverse drug
      reactions (ADRs). This thesis was confirmed by positive intradermal test with the
      same, but negative with other commercial product of benzylpenicillin potassium.
      Later chromatographic analysis shows drug contaminations. Thus an exclusion of
      allergy to drug impurities (and additives) is necessary for correct diagnosis
      benzylpenicillin allergy (and any active constituent). Furthermore, allergy to
      drug impurities (and additives) closely resemble cross-reactions or multiple
      chemical sensitivity syndrome (MCSS).

PMID- 15517939
TI  - [The prognostic significance of microalbuminuria in cardiovascular events].
AB  - Microalbuminuria is a useful marker for progression of renal damage in patients
      with diabetes. Many population studies demonstrated that microalbuminuria is
      associated with many risk factors of cardiovascular damage. Microalbuminuria is
      more and more frequently appreciated as a marker not only of diabetic nephropathy
      but also as a marker of increased risk of ischemic heart disease, cardiovascular
      events, in both diabetic and non-diabetic patients. Results of some of the
      studies quoted in this article support hypothesis that microalbuminuria reflects
      general damage of cardiovascular system and can be a marker of early changes in
      arteries.

PMID- 15517940
TI  - [Dysmetabolic syndrome].
AB  - This paper present definition, prevalence and inheritance of the metabolic
      syndrome. The dysmetabolic syndrome most likely results from interplay between
      several genes and affluent environment. The prevalence of the syndrome is also
      very age-dependent and higher in males than in females. In subjects with
      dysmetabolic syndrome the survival is reduced, particulary because of increased
      cardiovascular mortality. The dysmetabolic syndrome requires non-drug and drug
      treatment.

PMID- 15517941
TI  - [beta-blockers in the treatment of hypertension in diabetic patients].
AB  - Cardiovascular diseases and strokes are the main reasons of premature deaths in
      70% patients with non insulin-dependent and also insulin-dependent diabetes
      mellitus. Hypertension is 2 to 3 times more frequent in diabetic patients than in
      the rest of population. In the guidelines for management of hypertension in
      diabetes published this year beta-blockers are proposed together with the ACE
      inhibitors as the first-choice drugs. The latest studies did not confirm the risk
      of higher and prolonged hypoglycemia during cardioselective beta-adrenergic
      blocade, but the insulin-treated diabetics with hypoglycemia episodes in the past
      should be watched very carefully when given beta-blockers. It is emphasized, that
      beta-blockers are very useful especially in patients with diabetes mellitus,
      hypertension and coronary artery disease. In patients after myocardial infarction
      the advantages with treatment with beta-blockers dominate over the potential risk
      of adverse drug reactions.

PMID- 15517942
TI  - [Impaired glucose tolerance and the risk of cardiovascular death].
AB  - Hyperglycemia and type 2 diabetes are an independent risk factor of
      cardiovascular (CV) disorders of atherosclerotic etiology. Proatherosclerotic
      sequelae of hyperglycemia comprise oxidative stress caused by increased
      production of free radicals, activation of leucocyte-endothelium interactions,
      and protein glycosylation. According to current reccomendations diabetes is
      diagnosed when plasma glucose concentration exceeds 10.0 mmol/L in 2-hour
      standard oral glucose tolerance test, whereas the result of 6.7-9.9 mmol/L speaks
      for asymptomatic impaired glucose tolerance (IGT) which does not require
      treatment. However, several data sets and their meta-analyses are suggestive of
      that not only diabetes, but also IGT is associated with significantly increased
      risk of cardiovascular death. A recent report indicated also that glycosylated
      hemoglobin HbA(1c) level is a continuous and very strong risk factor for CV
      death. In view of these data therapeutic interventions for IGT shall be
      considered.

PMID- 15517943
TI  - [The role of platelet-derived growth factor A (PDGF-A) in hypertension and renal
      diseases. Part 1: Structure and regulation of the PDGF-A gene expression and its
      role in hypertension].
AB  - Platelet-derived growth factor is commonly known as a mitogen. There are four
      members of PDGF family known as PDGF-A chain, PDGF-B chain, PDGF-C chain and PDGF
      D chain, which in active forms are dimers. As far as two receptors PDGF-alphaR
      and PDGF-betaR are known to bind PDGF There is a difference in binding affinity
      of various forms of PDGF by those receptors. Two different transcripts are
      derived from PDGF-A gene by alternative splicing. Transcription of PDGF-A gene is
      under control of many factors. Many research data suggest a role for PDGF-A in
      smooth muscle cell hyperplasia in hypertension and atherosclerosis. Since
      inhibition of PDGF-A transcription by a specific ribozyme represses smooth muscle
      cell proliferation in arteries, introduction of gene therapy might be of value in
      the treatment of hypertension and its complications.

PMID- 15517944
TI  - [The role of platelet-derived growth factor A (PDGF-A) in hypertension and renal
      diseases. Part 2: a role of PDGF-A in kidney diseases].
AB  - Many studies have suggested deleterious effects of platelet-derived growth factor
      (PDGF) released by intrinsic renal cells during glomerulonephritis (GN). Increase
      in PDGF B chain expression has particularly been noted in glomeruli of patients
      with GN. Less known is the role of PDGF A chain both in the normal kidney and
      renal diseases. Several lines of evidence have indicated the involvement of PDGF
      A in renal graft rejection. Furthermore, an increased expression of PDGF-A has
      also been observed in the course of human diabetic nephropathy. Still, the role
      of PDGF-A in the development and progression of GN remains unclear.

PMID- 15517945
TI  - [Rheumatologic manifestations of hypothyroidism].
AB  - Rheumatologic manifestations are varied during the hypothyroidism. They can be
      articular, abarticular, muscular or osseous, consequences of an inappropriate
      hormonal secretion. Their diagnosis is easy when hypothyroidism is known, but
      they can be inaugural. Their evolution is favorable under substitute treatment.

PMID- 15517946
TI  - [Non alcoholic steatohepatitis: an emergent and potentially serious pathology].
AB  - Nonalcoholic steatohepatitis is an acquired liver disease, usually metabolic
      characterised by histologic lesions with steatosis, intralobular necrosis and
      inflammatory infiltrates. Liver biopsy findings are identical to those seen in
      alcoholic hepatitis. Nonalcoholic steatohepatitis is increasingly reported in
      industrial countries because of an increase of the prevalence of obesity and
      diabetes which are the most common risk factors of this disease. The diagnosis of
      nonalcoholic steatohepatitis is based on a confrontation between clinical and
      anatomic data and an exclusion of an excessive intake of alcohol and other
      hepatic disease. Liver biopsy has a prognosis and histologic benefit especially
      when there is risk factors of fibrosis. This disease is potentially severe with a
      potential risk for progression to cirrhosis. Progress in pathogenesis is noted
      but no definite therapy exist. The aim of this review is to indicate current
      knowledge for the gravity of nonalcoholic steatohepatitis and its consequence and
      to understand the pathogenesis to prevent cirrhosis.

PMID- 15517947
TI  - [Analysis of knowledge attitudes and practices of health care workers facing
      blood exposure accidents in a general surgery service].
AB  - In order to assess the degree of knowledge, attitudes and the personnel's
      practices exercising in a service of general surgery of the hospital Charles
      Nicolle of Tunis, concerning blood exposure accidents, we did a transverse survey
      during the month of January of the year 2002. A questionnaire has been addressed
      to 114 people while using the technique of the direct interview. The middle age
      of investigated is 35.7 years. The sex ratio is 0.7. Only the 2/3 declare have
      been vaccinated against the B hepatitis. The results show a good knowledge of the
      exposure risk to a communicable disease by blood (95.6%), but less good for the
      risk of contamination by the three viruses HBV, HCV and HIV. The resheathing of
      needles, considered like gesture to risk, is underestimated by 71.2% of
      investigated. The majority of investigated declare to know universal precaution
      principles (85.8%). However, to the maximum 4 measures only on the 10 advisable
      have been mentioned by investigated. The conduct to hold in case of blood
      exposure accident seems insufficiently known by our sample. It is represented, in
      78.8% of cases, in the application of disinfectants Betadine type or alcohol
      iodized, whereas the practice of a serology to the patient source is ignored
      completely. 75% of investigated having had a blood exposure accident lasting the
      last 12 months (n = 44) didn't declare their blood exposure accident and only
      11.4% declare to have undergone cares. Actions of information and formation, to
      the intention of the whole of the personnel of the service, on risks incurred by
      the nursing, gestures and procedures to risk, the universal precaution respect,
      the conduct to hold in case of a blood exposure accident, the interest of the
      declaration and the interest of the vaccination against the B hepatitis, are
      primordial.

PMID- 15517948
TI  - [Ischemic strokes in young adults].
AB  - OBJECTIVES: The purpose of this study was to determine etiologies and outcome of
      strokes in young adults. PATIENTS AND METHODS: We studied retrospectively 48
      cases of patients with transient ischemic attack or arterial ischemic stroke aged
      between 15 and 48 years admitted in the Neurology and Cardiology Departments of
      the University Hospital of Monastir from 1987 to 1996. The study variables
      included the full clinical spectrum, spanning historical, laboratory,
      radiological and outcome parameters. RESULTS: Thirty four were female and 14
      male, the mean age was 33 +/- 8.8 years, with a peak in the 4th decade. Our
      series is characterised by the higher incidence of cardioembolic dominated by
      prosthetic valve. 62.5% of patients had common vascular risk factors. Non
      atherosclerotic arteriopathies were observed in six cases uncommon etiologies of
      ischemic stroke (Moya-Moya disease, Takayasu's disease...). Etiology remain
      undetermined in four cases. Mortality rate was 8.5%. Reccurrences were observed
      in 12.5%. 29% of patients have recovered complete autonomy while 26% have
      conserved severe handicap. CONCLUSION: We found a higher incidence of
      cardioembolic diseases dominated by prosthetic valve.

PMID- 15517949
TI  - [Hyperprolactinemia in systemic lupus erythematosus. A prospective study of 38
      cases].
AB  - OBJECTIVE: To study prospectively the serum prolactin concentrations among
      patients with systemic lupus erythematosus and their possible relationship to
      disease activity and manifestations. METHODS: Serum prolactin levels were
      measured by radioimmunoassay in 38 patients with systemic lupus erythematosus and
      22 age matched controls. Patients with known secondary causes for
      hyperprolactinaemia, such as pregnancy, lactation, prolactinoma and taking
      medications known to induce prolactin secretion, were excluded from the study.
      Demographic, clinical and laboratory features of the patients were obtained.
      Patients were divided into two subgroups according to their disease activity.
      Mean prolactin levels from both groups were compared using student test, and
      prolactin from patients with systemic lupus erythematosus was correlated with
      variables of disease activity, including the Systemic Lupus Erythematosus Disease
      Activity Index (SLEDAI). RESULTS: Mean prolactin levels were higher in patients
      with systemic lupus erythematosus (15.4) than healthy controls (9.83); however,
      the difference did not reach statistical significance (p=). Hyperprolactinemia
      was found in 24 patients with systemic lupus erythematosus and 5 controls. The
      frequency of hyperprolactinaemia in systemic lupus erythematosus group was higher
      than healthy controls. No significant difference in mean prolactin levels was
      found between patients with active versus inactive disease (18.9 vs 18.5).
      CONCLUSION: Hyperprolactinaemia occurred significantly in patients with systemic
      lupus erythematosus, but did not correlate with disease activity.

PMID- 15517950
TI  - [Cystic fibrosis of the child].
AB  - Cystic fibrosis was regarded a long time as exceptional in the Nord Africaine
      population and in particular in Tunisia what was at the origin of the ignorance
      of its various diagnostic and therapeutic aspects in our country. Nevertheless,
      with the development of the means of the diagnosis, several cases of cystic
      fibrosis were diagnosed these last years what will pose true problems of
      assumption of responsibility of these children like illustrates it well our
      experiment in the pediatric department of Sfax university hospital. In 10 years
      going of 1991 to 2000 we reported 7 cases of cystic fibrosis in the pediatric
      department of Sfax university hospital. Our patients are 3 boys and 4 girls. The
      age of revelation of the disease varied from 3 months to 14 years with 4 years
      and 10 months an average age. All our patients had a respiratory symptomatology
      in the foreground. The evolution was marked by the death of 4 patients at an
      average age of 5 years and half whereas the 3 surviving patients for the moment
      are more or less balanced on the nutritional level, digestive and respiratory.
      Cystic fibrosis is not exceptional in our area, its assumption of responsibility
      therapeutic is difficult, and it requires the collaboration of several experts
      and a good compliance of the child and of his family.

PMID- 15517951
TI  - [Sonographic estimation of fetal weight at term: a proposal of a predictive score
      of a weight more than 4500 g].
AB  - Estimation of fetal weight at term is essential because of risks of macrosomic
      infant delivery. The purpose of this study is to assess sonographic prediction of
      macrosomia and especially in fetal weight (o) > 4500 g. MATERIAL AND METHOD: In a
      retrospective study on one year period, we analyzed sonography of 214 pregnant
      women at term having delivered macrosomic infants. From sensitivity, specificity
      and VPP found for each fetal measurement (abdominal transverse diameter: ATD,
      femur length: FL, and biparietal diameter :BPD) we tried to determine the best
      thresholds values that permit to suspect fetal weight more than 4500 g. RESULTS:
      Sensitivity of ATD (o) > 100 mm, FL (o) > 76 mm and BPD (o) > 94 mm in prediction
      of macrosomia were: 70.5%, 56% and 58.9% respectively. The most reliable and
      predictive thresholds for macrosomia more than 4500 g were: 105 mm, 78 mm and 98
      mm respectively for ATD, FL and BPD. In an other study, we have found that fundal
      height (o) > 37 cm is also predictive of such a macrosomia. So we have proposed a
      predictive score of fetal weight more than 4500 g, based on the best thresholds
      found for fundal height, ATD, FL and BPD.

PMID- 15517952
TI  - [Place of endoscopic variceal ligation for the prophylaxis of rebleeding from
      oesophageal varices. Prospective study about 102 cases].
AB  - The aim of this study was to assess the efficacy and morbidity of endoscopic
      variceal ligation for the prophylaxis of rebleeding from oesophageal varices.
      This work is a prospective study including 102 patients having had at least one
      episode of variceal bleeding. The mean age is 52.5 years. Oesophageal varices
      were eradicated in 83.3% of cases after an average of 3.5 sessions. Recurrence of
      oesophageal varices after eradication was observed in 22% after an average follow
      up of 7 months. 10 patients died before eradication of oesophageal varices from
      causes unrelated to the technique. The endoscopic variceal ligation is effective
      for eradication of oesophageal varices, with a low morbidity. This technique
      appears to be a method of choice in the prophylaxis of rebleeding from
      oesophageal varices.

PMID- 15517953
TI  - [A multiple myeloma long term survival case].
AB  - Multiple myeloma is a malignant plasma cells proliferation in the bone marrow
      leading to a monoclonal immunoglobulin hypersecretion. The survival duration of
      this disease ranges usually from 2 to 3 years. However, as this reported case, a
      long-term survival remains possible. A 29 year old woman was admitted to the
      internal medicine department for bone pain, weight loss and pathologic fractures.
      The clinical examination revealed an anaemia, a spinal compression (D10) and
      atrophia of quadriceps and gluteus muscle. The radiologic findings observed were
      multiple fractures. The bone marrow aspiration confirmed the plasmocytosis
      greater than 50%, with immature plasma cells and other lineages rarefication. The
      disease belonged to the stage III A of the Salmon and Durie classification.
      Chemotherapy with melphalan associated to prednisone was started with a two to
      three months biological and clinical follow-up. This treatment allowed 12 years
      survival. Because of this variety, the search for new prognostic factors would be
      relevant.

PMID- 15517954
TI  - [Short coupled variant of "torsades de pointes" and sudden death].
AB  - A case report of 38 year old man who experienced syncope and torsade de pointes
      is presented with the short coupled variant. The patient had a normal QT interval
      (QTC: 0.37 seconds) and multiform ventricular premature beats on the resting
      electrocardiogram. Under antiarrhythmic treatment (intravenous xylocaine),
      torsades de pointes suddenly appeared and cardiac arrest was followed. After
      cardioversion, sinus rhythm was restored. A cardiovascular disease was excluded,
      the echocardiography, the left and right ventricular angiography and
      coronarography were normal. Three months after, the patient presented at home a
      sudden cardiac death.

PMID- 15517955
TI  - [Cervico-facial lymphatic malformations in adults].
AB  - Lymphatic malformations are due to an abnormality in lymphatic development only
      rarely present in adults. Their prognosis is better than those of infants. We
      report 6 cases of lymphatic malformations of head and neck in adults reviewed
      from 1990 to 2001. The treatment was surgical in 5 cases. Surgical excision is
      the treatment of choice and reccurences are rare.

PMID- 15517956
TI  - [Angiomatoid fibrous histiocytoma: rare tumor of intermediate malignancy].
AB  - Angiomatoid fibrous histiocytoma is a rare tumour affecting young adults. Unlike
      conventional malignant fibrous histiocytoma, its extension is only local thus
      giving a good prognosis. We report the cases of a 9 year-old girl and a 16 year
      old boy presenting respectively, with an axillary tumour 5 cm of diameter and a
      paravertebral subcutaneous tumour 1.5 cm of diameter. In both cases, the
      diagnosis was not initially suspected. The treatment consisted in surgical
      resection.

PMID- 15517957
TI  - [Neuro-psychiatric disorders revealed pernicious disease without anemia. About
      three cases].
AB  - In addition to an anemic syndrome, pernicious disease can also include
      neuropsychiatric manifestations. We report here three cases diagnosed as
      pernicious disease revealed by neuropsychiatric symptoms and even without anemia.
      Our patients were made of a man and two women with a mean age of 55 years. They
      consulted for progressively worsening troubles of step which were related to a
      combined degeneration of the cord. This degeneration was associated to a
      cerebellar syndrome in one case. An isolated macrocytosis with a mean MGV at 109
      fl, was noticed allowing thus to evoke the Biermer pernicious disease. This
      diagnosis was confirmed by the marrow puncture which showed a medullar
      megaloblastosis in two cases and an erythroblastic nucleocytoplasmic maturation's
      asynchronism. Treated by vitamin B12, the evolution was favorable in two cases
      with a total neurological recovery after six months in two patients. One patient
      died after six days of treatment following an acute myocardial infarction. If
      faced to symptoms made of a combined degeneration of the spinal card, a
      peripheral neuropathy and/or psychiatric troubles, pernicious disease is a
      diagnosis that we must evoke even in absence of anemia.

PMID- 15517958
TI  - [Acrania ultrasonography diagnosis: a rare embryologic malformation].
AB  - The authors report a case of acrania diagnosed on antenatal period in a routine
      morphologic ultrasonography at 19 weeks of intra uterine gestation on a 20-year
      old patient, gravida 1, para 0. Acrania associated with exencephaly is a rare and
      lethal malformation characterized by a defect of development of the flat bones of
      the scalp whereas cerebral tissue is present often abnormal. Ultrasonography had
      allowed to find besides the cerebral malformation, spinal and visceral fetal
      malformations as well as cord abnormality that included only two vessels.

PMID- 15517959
TI  - DNA nanotechnology.

PMID- 15517960
TI  - Apoptosis: one way to die.

PMID- 15517961
TI  - PCR-based assay for mating type and diploidy in Chlamydomonas.

PMID- 15517962
TI  - Microarray approach for cloned library quality assessment and the comprehensive
      identification of positives from library screens.

PMID- 15517963
TI  - RNA isolation from siliques, dry seeds, and other tissues of Arabidopsis
      thaliana.

PMID- 15517964
TI  - Tetracycline derivatives: alternative effectors for Tet transregulators.

PMID- 15517965
TI  - Visualization of chromosomes and nuclear envelope in living cells for molecular
      dynamics studies.

PMID- 15517966
TI  - High efficiency DNA mutagenesis mediated by using in vitro transcription, DNase I
      digestion, and RT-PCR.

PMID- 15517967
TI  - Comment on Blachinsky et al. "Procedure for controlling number of repeats,
      orientation, and order during cloning of oligonucleotides" Biotechniques 36:933
      936 (June 2004).

PMID- 15517968
TI  - In situ imaging of mitochondrial outer-membrane pores using atomic force
      microscopy.
AB  - Here we describe a technique for imaging of the outer contours of the
      mitochondrial membrane using atomic force microscopy, subsequent to or during a
      toxic or metabolic challenge. Pore formation in both glucose-challenged and 1,3
      dinitrobenzene (DNB)-challenged mitochondria was observed using this technique.
      Our approach enables quantification of individual mitochondrial membrane pore
      formations. With this work, we have produced some of the highest resolution
      images of the outer contours of the in situ mitochondrial membrane published to
      date. These are potentially the first images of the component protein clusters at
      the time of formation of the mitochondrial membrane transition pore in situ. With
      the current work, we have extended the application of atomic force microscopy of
      mitochondrial membranes to fluid imaging. We have also begun to correlate 3-D
      surface features of mitochondria dotted with open membrane pores with features
      previously viewed with electron microscopy (EM) of fixed sections.

PMID- 15517969
TI  - Profiling microRNA expression using sensitive cDNA probes and filter arrays.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs (approximately 22 nucleotides) that
      have recently emerged as important regulators of gene expression in both plants
      and animals. With few exceptions, however, the target genes and the expression
      levels of most miRNAs are unknown. Here we show that direct random-primed cDNA
      synthesis on either chemically synthesized small RNAs (21-22 nucleotides) or gel
      purified mature miRNAs from human cells can produce specific and sensitive full
      length cDNA probes. Using oligonucleotide filter arrays, we demonstrate that the
      internally labeled cDNA probes are sensitive for detecting differential miRNA
      expression between untreated and O-tetradecanoylphorbol-13-acetate (TPA)-treated
      HL60 cells. The present study should facilitate a high-throughput analysis of
      miRNA expression between samples.

PMID- 15517970
TI  - Oligonucleotide microarray analysis of aminoallyl-labeled cDNA targets from
      linear RNA amplification.
AB  - Single-stranded long oligonucleotide-based (50- to 70-mer) microarrays offer
      several advantages over conventional cDNA microarrays. These include the easy
      preparation of the probes, low cost of array production, and low cross
      contamination during probe handling. However, the application of oligonucleotide
      microarrays for the analysis of global gene expression with small amounts of
      total RNA using the conventional oligo(dT)-T7 promoter-based amplification is
      hampered by the single-stranded nature (sense strand) of oligonucleotide probes
      in microarrays. In this report, we describe modified RNA amplification methods
      generating antisense-labeled cDNA targets and a successful application for
      oligonucleotide microarray gene expression analysis. In the first round, mRNA was
      amplified linearly with oligo(dT)24T7-primed reverse transcription and in vitro
      transcription by T7 RNA polymerase. In the second round, random 9-mer T3 primers
      and T3 RNA polymerase were used to generate sense-strand amplified RNA (aRNA).
      Fluorescently labeled cDNA targets were generated from the aRNA and hybridized to
      the oligonucleotide microarrays. Our data show that the amplification provides
      highly reproducible results, as evidenced by a significant correlation between
      the amplified and nonamplified samples. We also demonstrate that amplification of
      RNA derived from laser-microdissected tumor samples reproduced the gene
      expression profiles that were obtained from total RNA isolated from the same
      samples.

PMID- 15517971
TI  - Automated multi-well device to measure transepithelial electrical resistances
      under physiological conditions.
AB  - Measurement of transendothelial or transepithelial electrical resistances (TERs)
      is a straightforward in situ experimental approach to monitor the expression or
      modulation of barrier-forming cell-to-cell contacts (tight junctions) in cultured
      cells grown on porous filters. Although widely accepted, there is currently no
      device available to automatically measure the time course of TERs under ordinary
      cell culture conditions (37 degrees C, 5% or 10% CO2). This paper describes a
      development from our laboratory that is capable of following in parallel the TERs
      of several filter-grown cell layers with time and in an entirely computer
      controlled fashion. The cell cultures can be followed even in long-term
      experiments without any manual assistance or opening of the incubator Besides
      reading TER values, this approach also returns the electrical capacitance of the
      cell layers, which is indicative of the expression of microvilli and other
      membrane extrusions. The device is based on reading the frequencydependent
      impedance of the cell layer, followed by equivalent circuit modeling to extract
      the cell-related parameters. It is compatible with several multi-well formats (up
      to 96 wells) and controlled by custom-designed software that reads, analyzes, and
      presents the data.

PMID- 15517972
TI  - Ultra-fast high-resolution agarose electrophoresis of DNA and RNA using low
      molarity conductive media.
AB  - Current DNA electrophoretic solutions employ high ionic concentrations and
      require long electrophoretic run times. Here we demonstrate that high and low
      molecular weight double-stranded DNA, single-stranded DNA (ssDNA), and RNA can be
      separated rapidly in agarose-based low-molarity conductive media. Separation of
      small DNA fragments was optimized by substituting 1-mM solutions of alkali metals
      or a nonbiological amine that distributed voltage with a minute current. These
      ultra-dilute solutions can separate DNA at least 15-fold faster Low-molarity
      media at 5-10 mM adequately separated RNA and larger DNA fragments as well. These
      novel media reduce the Joule heating of the electrophoretic system and allow for
      easy-to-use, ultra-fast separation of DNA fragments.

PMID- 15517973
TI  - Biotinylated tags for recovery and characterization of ribonucleoprotein
      complexes.
AB  - Determining the in vivo targets of RNA-binding proteins and characterizing the
      posttranscriptional networks in which they participate constitute major
      challenges in the post-genomic era. An important step in this direction is the
      development of methods that permit efficient recovery of ribonucleoprotein (RNP)
      complexes. We present an improved methodology for efficient isolation of
      mammalian cell RNPs in which a biotin acceptor peptide (BAP) is used to tag RNA
      binding proteins. BAP-tagged RNA-binding proteins can be biotinylated in vivo by
      co-expression of the Escherichia coli BirA enzyme. RNP recovery was obtained
      using streptavidin sepharose beads, and messenger RNAs (mRNAs) were identified
      using multiprobe RNase protection assays and cDNA microarrays. Using this
      approach we efficiently recovered and quantified RNAs bound to cytoplasmic
      poly(A)-binding protein (PABP) and to nuclear human transformer 2 (hTra-2) with
      minimal background.

PMID- 15517974
TI  - Real-time quantitative PCR-based system for determining transgene copy number in
      transgenic animals.
AB  - In this paper, we describe a rapid and accurate real-time quantitative PCR-based
      system to determine transgene copy number in transgenic animals. We used the 2(
      deltadeltaCt) method to analyze different transgenic lines without the
      requirement of a control sample previously determined by Southern blot analysis.
      To determine the transgene copy number in several mouse lines carrying a goat
      beta-Lactoglobulin transgene, we developed a TaqMan assay in which a goat genomic
      DNA sample was used as a calibrator. Moreover, we used the glucagon gene as a
      reference control because this gene is highly conserved between species and
      amplifies with the same efficiency and sensitivity in goat as in mouse. With this
      assay, we provide an alternative simple method to determine the transgene copy
      number, avoiding the traditional and tedious blotting techniques. The assay's
      discrimination ability from our results is of at least six copies and, similar to
      the limitations of the blotting techniques, the accuracy of the quantification
      diminishes when the transgene copy number is high.

PMID- 15517975
TI  - Proteomic analyses using an accurate mass and time tag strategy.
AB  - An accurate mass and time (AMT) tag approach for proteomic analyses has been
      developed over the past several years to facilitate comprehensive high-throughput
      proteomic measurements. An AMT tag database for an organism, tissue, or cell line
      is established by initially performing standard shotgun proteomic analysis and,
      most importantly, by validating peptide identifications using the mass
      measurement accuracy of Fourier transform ion cyclotron resonance (FTICR) mass
      spectrometry (MS) and liquid chromatography (LC) elution time constraint.
      Creation of an AMT tag database largely obviates the need for subsequent MS/MS
      analyses, and thus facilitates high-throughput analyses. The strength of this
      technology resides in the ability to achieve highly efficient and reproducible
      one-dimensional reversed-phased LC separations in conjunction with highly
      accurate mass measurements using FTICR MS. Recent improvements allow for the
      analysis of as little as picrogram amounts of proteome samples by minimizing
      sample handling and maximizing peptide recovery. The nanoproteomics platform has
      also demonstrated the ability to detect >10(6) differences in protein abundances
      and identify more abundant proteins from subpicogram amounts of samples. The AMT
      tag approach is poised to become a new standard technique for the in-depth and
      high-throughput analysis of complex organisms and clinical samples, with the
      potential to extend the analysis to a single mammalian cell.

PMID- 15517976
TI  - Mass spectrometry provides accurate characterization of two genetic marker types
      in Bacillus anthracis.
AB  - Epidemiological and forensic analyses of bioterrorism events involving Bacillus
      anthracis could be improved if both variable number tandem repeats (VNTRs) and
      single nucleotide polymorphisms (SNPs) could be combined on a single analysis
      platform. Here we present the use of electrospray ionization Fourier transform
      ion cyclotron resonance mass spectrometry (ESI-FTICR-MS) to characterize 24
      alleles from 6 VNTR loci and 11 alleles from 7 SNP loci in B. anthracis. The
      results obtained with ESI-FTICR-MS were consistent with independent results
      obtained from traditional approaches using electrophoretic detection of
      fluorescent products. However, ESI-FTICR-MS improves on the traditional
      approaches because it does not require fluorescent labeling of PCR products,
      minimizes post-PCR processing, obviates electrophoresis, and provides unambiguous
      base composition of both SNP and VNTR PCR products. In addition, ESI-FTICR-MS
      allows both marker types to be examined simultaneously and at a rate of
      approximately 1 sample per min. This technology represents a significant advance
      in our ability to rapidly characterize B. anthracis isolates using VNTR and SNP
      loci.

PMID- 15517978
TI  - Automated high-throughput sex-typing assay.

PMID- 15517977
TI  - Organism identification using a genome sequence-independent universal microarray
      probe set.
AB  - There has been increasing interest and efforts devoted to developing biosensor
      technologies for identifying pathogens, particularly in the biothreat area. In
      this study, a universal set of short 12- and 13-mer oligonucleotide probes was
      derived independently of a priori genomic sequence information and used to
      generate unique species-dependent genomic hybridization signatures. The probe set
      sequences were algorithmically generated to be maximally distant in sequence
      space and not dependent on the sequence of any particular genome. The probe set
      is universally applicable because it is unbiased and independent of hybridization
      predictions based upon simplified assumptions regarding probe-target duplex
      formation from linear sequence analysis. Tests were conducted on microarrays
      containing 14,283 unique probes synthesized using an in situ light-directed
      synthesis methodology. The genomic DNA hybridization intensity patterns
      reproducibly differentiated various organisms (Bacillus subtilis, Yersinia
      pestis, Streptococcus pneumonia, Bacillus anthracis, and Homo sapiens), including
      the correct identification of a blinded "unknown" sample. Applications of this
      method include not only pathological and forensic genome identification in
      medicine and basic science, but also potentially a novel method for the discovery
      of unknown targets and associations inherent in dynamic nucleic acid populations
      such as represented by differential gene expression.

PMID- 15517979
TI  - In vivo analysis of DNA methylation patterns recognized by specific proteins:
      coupling CHIP and bisulfite analysis.
AB  - The three-way connection between DNA methylation, chromatin configuration, and
      transcriptional regulation is under increasing attention, but the fine rules
      governing the epigenetic control are still poorly understood. In several studies,
      the authors have concluded that the methylation status of CpG sites could be
      critical for the binding of factors to DNA and, consequently, for chromatin
      conformation. We tested the possibility that a novel technical approach combining
      chromatin immunoprecipitation and bisulfite genomic sequencing analysis (ChIP-BA)
      could provide useful information on the role of specific CpG methylation patterns
      in driving the association in vivo of proteins to given genomic regions. Our
      results show that ChIP-BA permits the establishment in vivo of the methylation
      patterns required for the binding of a methyl-CpG binding protein and, in
      addition, can potentially identify methylation patterns that do not allow a
      protein to bind specific genomic regions. Possible fields of application are
      discussed. We believe that wide use of ChIP-BA could make possible the
      exploration of a novel aspect of the intricate epigenetic web.

PMID- 15517980
TI  - Vectorettes for long chromosome walking in genomic DNA of the human p53 gene.
AB  - Chromosome walking in mammalian DNA by vectorette PCR is not always very
      specific, and the walks have been limited to distances <1 kb. To improve the
      method, we have designed new vectorettes, which unlike the currently used ones
      have very little repetitive sequences or homology with known DNA sequences of
      various origins in the data banks. We have tested these new vectorettes for
      chromosome walking in human p53 tumor suppressor gene, human tissue-type
      plasminogen activator gene, and mouse stanniocalcin gene with good success. In
      chromosome walking of the human p53 gene, we isolated gene-specific fragments of
      2.4. kb, and by walking in a bacterial artificial chromosome (BAC) clone carrying
      the mouse stanniocalcin gene, we isolated fragments up to about 7 kb in size. We
      further sequenced the 5' region of the p53 gene and found that the nucleotides
      upstream of -1009 are transcribed in antisense orientation into a messenger RNA
      (mRNA) (flj10385) encoding a putative serine/threonine kinase.

PMID- 15517981
TI  - DNA nucleic acid sequence-based amplification-based genotyping for polymorphism
      analysis.
AB  - Nucleic acid sequence-based amplification (NASBA) is a sensitive isothermal
      transcription-based amplification method known to be a suitable tool for RNA
      research. We demonstrate that NASBA technology can be applied to single
      nucleotide polymorphism (SNP) analysis using human genomic DNA as a template.
      Combination of DNA NASBA with multiplex hybridization of specific molecular
      beacons makes it possible to unambiguously discriminate the presence of the SNP
      of interest. This protocol is easy-to-use, robust, and makes it possible to
      rapidly detect single nucleotide substitutions in clinical or cell line DNA
      sequences using a large range of DNA input. Such a real-time genotyping DNA NASBA
      assay can find broad application in clinical diagnostics.

PMID- 15517982
TI  - "Natural" versus regular antibodies.

PMID- 15517983
TI  - Kinetic study on conformational change in a single molecular species, beta3, of
      beta-conglycinin in an acidic ethanol solution.
AB  - The conformational change in a single molecular species, beta3, of beta
      conglycinin in an acidic ethanol solution was kinetically studied by the stopped
      flow technique, utilizing the intrinsic fluorescence of proteins and the
      fluorescence of 1-anilinonaphthalene-8-sulfonic acid (ANS) bound to the proteins.
      The time-course of the intrinsic fluorescence changes clearly showed the rate of
      conformational change below and above 25% ethanol to be quite different from each
      other. ANS could bind well to the protein in an ethanol concentration range of 15
      25%. However, the rate of conformational change of the protein corresponding to
      that for ANS binding could not be obtained at less than 25% ethanol, while the
      rate of conformational change agreed well with that for ANS binding at more than
      25% ethanol. In addition, the process showing the greatest and slowest ANS
      binding was not apparent in the denaturation of beta-conglycinin under the
      conditions employed. These results lead to the conclusions that the beta
      conglycinin structure could be maintained in the mild molten globule-like
      denaturation state, and that various tertiary structural changes could take place
      without any significant effect on the high sensitivity of intrinsic fluorescence
      after the secondary structural changes.

PMID- 15517984
TI  - Characterization of toxin complex produced by a unique strain of Clostridium
      botulinum serotype D 4947.
AB  - A unique strain of Clostridium botulinum, serotype D 4947 (D-4947), produces a
      considerable amount of a 650 kDa toxin complex (L-TC) and a small amount of a 280
      kDa M-TC, a 540 kDa TC, and a 610 kDa TC. The complexes are composed of only un
      nicked components, including neurotoxin (NT), nontoxic nonhemagglutinin (NTNHA)
      and hemagglutinin subcomponents (HA-70, HA-33 and HA-17). Unlike other NTs from
      all serotype strains, separation of D-4947 NT from L-TC, except for M-TC, during
      chromatography required highly alkaline conditions around pH 8.8. The separated
      NT and NTNHA/HAs complex can be reconstituted to L-TC that is indistinguishable
      from the parent L-TC with respect to toxicity, hemagglutination activity and gel
      filtration profile. The isoelectric points of NT and NTNHA/HAs were close
      together depending on the number of HA-33/17 molecules. We have established a new
      method to separate the unique D-4947 NT from the complex, which will yield
      valuable information on structure of botulinum toxin.

PMID- 15517985
TI  - Crystal structure of the pig pancreatic alpha-amylase complexed with rho
      nitrophenyl-alpha-D-maltoside-flexibility in the active site.
AB  - The X-ray structure analysis of a crystal of pig pancreatic alpha-amylase soaked
      with a rho-nitrophenyl-alpha-D-maltoside (pNPG2) substrate showed a pattern of
      electron density corresponding to the binding of a rho-nitrophenol unit at
      subsite -2 of the active site. Binding of the product to subsite -2 after
      hydrolysis of the pNPG2 molecules, may explain the low catalytic efficiency of
      the hydrolysis of pNPG2 by PPA. Except a small movement of the segment from
      residues 304-305 the typical conformational changes of the "flexible loop" (303
      309), that constitutes the surface edge of the substrate binding cleft, were not
      observed in the present complex structure. This result supports the hypothesis
      that significant movement of the loop may depend on aglycone site being filled
      (Payan and Qian, J. Protein Chen. 22: 275, 2003). Structural analyses have shown
      that pancreatic alpha-amylases undergo an induced conformational change of the
      catalytic residue Asp300 upon substrate binding; in the present complex the
      catalytic residue is observed in its unliganded orientation. The results suggest
      that the induced reorientation is likely due to the presence of a sugar unit at
      subsite -1 and not linked to the closure of the flexible surface loop. The
      crystal structure was refined at 2.4 A resolution to an R factor of 17.55% (Rfree
      factor of 23.32%).

PMID- 15517986
TI  - Thermal and alkaline denaturation of bovine beta-casein.
AB  - The secondary structure of bovine beta-casein was characterized using circular
      dichroism (CD) and FTIR spectroscopies under physiologically relevant conditions.
      Analytical ultracentrifugation technique was used to follow the highly
      temperature, pH and concentration dependent self-association behavior. CD
      measurements provide convincing evidence for short segments of polyproline II
      like structures in beta-casein in addition to a wide range of secondary structure
      elements, such as 10-20% alpha-helix, approximately 30% turns, 32-35% extended
      sheet. Results obtained at extreme pH (10.5) revealed structural destabilization
      in the monomeric form of the protein. At least four distinct structural
      transitions at 10, 33, 40 and 78 degrees C were observed at pH 6.75 by CD
      analysis, compared to only two transitions, 26 and 40 degrees C, at pH 10.5.
      Calculations from analytical ultracentrifugation suggest that the transitions at
      lower temperature (< or = 30 degrees C) occur primarily in the monomer. It is
      hypothesized that the transition at 10 degrees C and neutral pH may represent a
      general conformational change or cold denaturation. Those middle ranged
      transitions, i.e. 33 and 40 degrees C are more likely the reflection of
      hydrophobic changes in the core of beta-casein. As beta-casein undergoes self
      association and increases in size, the transition at higher temperature (78
      degrees C) is perhaps caused by the apparent conformational change within the
      micelle-like polymers. It has been shown that beta-casein binds the hydrophobic
      fluorescent probe ANS with high affinity in much similar fashion to molten
      globular proteins. The effect of urea denaturation on the bound complex
      effectively supports this observation.

PMID- 15517987
TI  - Purification and biochemical characterization of asclepain c I from the latex of
      Asclepias curassavica L.
AB  - In this work we report the isolation, purification and characterization of a new
      protease from latex of Asclepias curassavica L. Crude extract (CE) was obtained
      by gathering latex on 0.1 M citric-phosphate buffer with EDTA and cysteine with
      subsequent ultracentrifugation. Proteolytic assays were made on casein or
      azocasein as substrates. Caseinolytic activity was completely inhibited by E-64.
      Stability at different temperatures, optimum pH and ionic strength were evaluated
      by measuring the residual caseinolytic activity at different times after the
      incubation. CE showed the highest caseinolytic activity at pH 8.5 in the presence
      of 12 mM cysteine. CE was purified by cation exchange chromatography (FPLC). Two
      active fractions, homogeneous by SDS-PAGE, were isolated. The major purified
      protease (asclepain cI) showed a molecular mass of 23.2 kDa by mass spectrometry
      and a pI higher than 9.3. The N-terminal sequence showed a high similarity with
      those of other plant cysteine proteinases. When assayed on N-alpha-CBZ-aminoacid
      p-nitrophenyl esters, the enzyme showed higher preference for the glutamine
      derivative. Determinations of kinetic parameter (km and Kcat) were performed with
      PFLNA.

PMID- 15517988
TI  - A substrate-phage approach for investigating caspase specificity.
AB  - We have developed a substrate-phage approach for examining the substrate
      specificities of an important group of proteases involved in apoptosis--the
      caspases. After establishing selection conditions with caspases-3 and caspase-8
      vs control substrate-phage, we sorted X4 and X6 diversity libraries, identified
      consensus motifs that agree with previously defined caspase substrate motifs,
      confirmed the selection of active substrates using synthetic peptide rate assays
      under a range of buffer conditions, and compared kinetic parameters for selected
      substrates. The libraries produced some variations on the canonical motifs. From
      caspase-3 selections, a phage-derived synthetic peptide, DLVD, was hydrolyzed up
      to 170% faster than the canonical substrate DEVD. The P4 Asp residue was
      essential for good protease-sensitivity, but even substrates with substitutions
      at P4 were selected by phage and shown to be hydrolyzed. Caspase-8 selections, as
      expected, yielded predominantly clones containing a Glu at P3. In this case, the
      most frequent phage-derived peptide, LEVD, was cleaved at a rate of only 20% of
      the canonical caspase-8 substrate LETD. However, based on substitutions observed
      in the phage selectants at P4, a substrate peptide, AETD, was designed and shown
      to be hydrolyzed up to 160% faster than LETD. We consider factors that may
      contribute to differences in caspase substrate-phage selections vs synthetic
      peptide studies on the caspases, and suggest that the two approaches may offer
      complementary information.

PMID- 15517989
TI  - Detection of pairwise residue proximity by covariation analysis for 3D-structure
      prediction of G-protein-coupled receptors.
AB  - G-protein-coupled receptor (GPCR) is one of the most important targets for
      medicines. Homology modeling based on the crystal structure of bovine rhodopsin
      is currently the most frequently used method for GPCR targeted drug design.
      Information about residue-residue contacts and the structural specificity in the
      subfamily is essential for constructing more precise 3D structures, to
      distinguish the structural differences between the template and targets. In this
      study, we adopted the covariation analysis to extract information about residue
      residue interactions from the amino acid sequence. In the opsin family, a large
      number of adjacent covarying residue pairs were detected. The detected residue
      pairs have a strong tendency to gather in some regions important for the
      structure and function. These results suggest that the covariation analysis is
      practically utilized to detect adjacent residue pairs and also to apply for
      predicting functional sites. Analyses of other GPCR subfamilies, olfactory
      receptor and chemokine receptor families, demonstrated that some adjacent
      covarying residue pairs were common. Thus, the covariation analysis has
      possibilities in the substantial improvement of the 3D-structure modeling of
      GPCRs and in the detection of functional sites such as the ligand-binding sites.

PMID- 15517990
TI  - Analysis of the maize polyubiquitin-1 promoter heat shock elements and generation
      of promoter variants with modified expression characteristics.
AB  - The maize polyubiquitin-1 (Ubi-1) promoter is one of a few select promoters used
      to express foreign genes in monocots, such that recombinant proteins can be
      produced at commercially viable levels. Modifying the activity, specificity and
      responsiveness of such promoters provides a means to achieve desired levels and
      patterns of expression of genes encoding target products. Ubi-1 is constitutively
      expressed but is further induced by heat shock. The promoter contains two
      overlapping sequences with similarity to defined heat shock elements and we show
      that these sequences are also present upstream of the Ubi-1 homologue isolated
      from teosinte. Both the maize and teosinte promoters can mediate a heat shock
      response in transgenic maize. We have dissected the overlapping maize Ubi-1
      promoter heat shock elements and demonstrate that the 3' element is required to
      mediate a heat shock response. The Ubi-1 promoter is particularly active in
      tissues consisting of rapidly dividing cells, and within the seed it is strongly
      biased towards driving expression in the embryo. However, replacement of the heat
      shock elements with a trimer of a basic domain/leucine zipper factor binding site
      of a pea lectin promoter shifts the balance in seed expression towards the
      endosperm. The Ubi-1 variants described here differ in their overall activity in
      the seed, but they all show potential for driving high levels of heterologous
      gene expression in maize.

PMID- 15517991
TI  - Production of transgenic tilapia with Brockmann bodies secreting [desThrB30]
      human insulin.
AB  - BACKGROUND: Tilapia are commercially important tropical fish which, like many
      teleosts, have anatomically discrete islet organs called Brockmann bodies. When
      transplanted into diabetic nude mice, tilapia islets provide long-term
      normoglycemia and mammalian-like glucose tolerance profiles. METHODS: Using site
      directed mutagenesis and linker ligation we have "humanized" the tilapia insulin
      gene so that it codes for [desThrB30] human insulin while maintaining the tilapia
      regulatory sequences. Following microinjection into fertilized eggs, we screened
      DNA isolated from whole fry shortly after hatching by PCR. Positive fish were
      grown to sexual maturity and mated to wild-types and positive Fl's were further
      characterized. RESULTS: Human insulin was detected in both serum and in the
      clusters of beta cells scattered throughout the Brockmann bodies. Surrounding non
      beta cells as well as other tissues were negative indicating beta cell specific
      expression. Purification and sequencing of both A-and B-chains verified that the
      insulin was properly processed and humanized. CONCLUSIONS: After extensive
      characterization, transgenic tilapia could become a suitable, inexpensive source
      of islet tissue that can be easily mass-produced for clinical islet
      xenotransplantation. Because tilapia islets are exceedingly resistant to hypoxia
      by mammalian standards, transgenic tilapia islets should be ideal for
      xenotransplantation using immunoisolation techniques.

PMID- 15517992
TI  - T7 RNA polymerase-directed expression of an antibody fragment transgene in
      plastids causes a semi-lethal pale-green seedling phenotype.
AB  - A T7 promoter-controlled transgene, AbL, encoding a camel single-domain antibody
      fragment that binds to the model antigen chicken egg-white lysozyme was
      introduced into the plastid genome of tobacco. AbL expression was activated in
      the transplastomic line by introducing a nuclear transgene, ST7, encoding a light
      regulated plastid-targeted T7RNAP by cross-pollination. The resulting AbL x ST7
      progeny seedlings developed a pale-green phenotype and ceased growth soon after
      germination. High levels of AbL transcripts accumulated in AbL x ST7 seedlings
      and expression of functional AbL antibody was detected by ELISA. Transplastomic
      AbL plants were also crossed with nuclear-transformed tobacco plants containing a
      salicylic acid-inducible transgene encoding a plastid-targeted T7RNAP (PR-T7
      transgene). The resulting AbL x PR-T7 progeny were wild-type in appearance but
      were slow growing and prone to wilting even when provided with adequate water.
      Although AbL transcription was inducible by treating AbL x PR-T7 leaves with
      salicylic acid, high levels of T7RNAP-dependent AbL transcripts also accumulated
      in the absence of induction. However, AbL antibody did not accumulate at levels
      detectable by immunoblotting or ELISA in AbL x PR-T7 plants despite the fact that
      total leaf RNA containing AbL transcripts was capable of directing AbL antibody
      synthesis in an E. coli-derived in vitro translation system.

PMID- 15517993
TI  - Quantitative phenotyping as an efficient means to estimate C-cell number in a
      knock-in mouse model of MEN2B.
AB  - Over the last two decades we have witnessed the generation of hundreds, if not
      thousands, of lines of genetically altered mice, large numbers of which are being
      produced in order to model human disease. Given that their creation is still
      rather technically demanding and labour intensive, the time taken analysing the
      resultant phenotypes should be such that the maximal amount of information can be
      gleaned efficiently in an unbiased manner so as to be as close to the 'true'
      value as possible. In an attempt to characterise a cell-specific phenotype in a
      genetically defined knock-in mouse model of multiple endocrine neoplasia type 2B
      (MEN2B) we used a modern, unbiased, stereological approach called the optical
      fractionator to estimate total cell number in 3-D space. By applying a sampling
      technique to tissue blocks in a systematic random uniform manner, we demonstrate
      that the total number of calcitonin-immunoreactive C-cells in the thyroid glands
      of littermate mice harbouring activating mutations in one or both alleles of ret
      does not vary significantly (p = 0.46) from an unbiased estimate of 23,000 in
      wild-type controls; likewise, neither does mean thyroid volume (p = 0.78) when
      estimated using Cavalieri's principle. We demonstrate that the variation
      associated with the quantitative phenotyping method is negligible. Using this
      efficient, unbiased stereological method our results provide new insights into
      cell number and positioning with consequences for both normal and disease states.
      In summary, this unbiased stereological technique is conceptually simple, can be
      applied efficiently, and is pertinent to quantitating a wide variety of cell
      phenotypes thereby bridging specialisation boundaries. We propose the adoption of
      this technique to mouse experimental geneticists and recommend its horizontal
      transmission across all fields within experimental biology.

PMID- 15517994
TI  - A comparison of constitutive promoters for expression of transgenes in alfalfa
      (Medicago sativa).
AB  - The activity of constitutive promoters was compared in transgenic alfalfa plants
      using two marker genes. Three promoters, the 35S promoter from cauliflower mosaic
      virus (CaMV), the cassava vein mosaic virus (CsVMV) promoter, and the sugarcane
      bacilliform badnavirus (ScBV) promoter were each fused to the beta-glucuronidase
      (gusA) gene. The highest GUS enzyme activity was obtained using the CsVMV
      promoter and all alfalfa cells assayed by in situ staining had high levels of
      enzyme activity. The 35S promoter was expressed in leaves, roots, and stems at
      moderate levels, but the promoter was not active in stem pith cells, root
      cortical cells, or in the symbiotic zones of nodules. The ScBV promoter was
      active primarily in vascular tissues throughout the plant. In leaves, GUS
      activity driven by the CsVMV promoter was approximately 24-fold greater than the
      activity from the 35S promoter and 38-fold greater than the activity from the
      ScBV promoter. Five promoters, the double 35S promoter, figwort mosaic virus
      (FMV) promoter, CsVMV promoter, ScBV promoter, and alfalfa small subunit Rubisco
      (RbcS) promoter were used to control expression of a cDNA from Trichoderma
      atroviride encoding an endochitinase (ech42). Highest chitinase activity in
      leaves, roots, and root nodules was obtained in plants containing the CsVMV:ech42
      transgene. Plants expressing the endochitinase were challenged with Phoma
      medicaginis var. medicaginis, the causal agent of spring black stem and leaf spot
      of alfalfa. Although endochitinase activity in leaves of transgenic plants was 50
      to 2650-fold greater than activity in control plants, none of the transgenic
      plants showed a consistent increase in disease resistance compared to controls.
      The high constitutive levels of both GUS and endochitinase activity obtained
      demonstrate that the CsVMV promoter is useful for high-level transgene expression
      in alfalfa.

PMID- 15517995
TI  - Rederivation of transgenic and gene-targeted mice by embryo transfer.
AB  - Research on genetically engineered mice provides insights into the etiology,
      therapy, and genetic basis of human diseases. An important variable that affects
      the results of mouse studies is the health status of the animals. Pathogen
      burdens may confound observations and obscure underlying mechanisms. Mouse
      resource centers frequently rederive infected mouse strains. We review our
      experience on the use of a well-established technique, embryo transfer to
      rederive infected mouse strains. The following mouse pathogens were eliminated by
      embryo transfer: Mouse Parvovirus, Mouse Hepatitis Virus, Mouse Rotavirus, Mouse
      Encephalomyelitis Virus, Mouse Adenovirus, Helicobacter species, endoparasites,
      and ectoparasites. We rederived transgenic mouse lines, gene-targeted mouse
      lines, and lines with spontaneous mutations. In the majority of strains,
      fertilized eggs for embryo transfer were obtained by mating superovulated egg
      donors with males of the desired genotype. A total of 309 embryo transfers were
      performed to rederive 96 mouse strains. The pregnancy rate was 76%; 1996 pups
      were born, of which 43% carried the desired genotype. We performed 44 additional
      embryo transfers to rederive 15 other strains. The pregnancy rate was lower (45%)
      and none of the 135 pups carried the desired genotype. Although we successfully
      eliminated the pathogens in all transfers, we were unable to obtain pups with the
      desired genotype in 15 of 111 mouse lines. Multiple factors affect the efficiency
      of rederivation by embryo transfer. They include the response to superovulation
      by embryo donors, the number and age of stud males, the yield of fertilized eggs,
      the number of embryo transfers, and genotyping.

PMID- 15517996
TI  - Effect of down-regulation of ethylene biosynthesis on fruit flavor complex in
      apple fruit.
AB  - The role of ethylene in regulating sugar, acid, texture and volatile components
      of fruit quality was investigated in transgenic apple fruit modified in their
      capacity to synthesize endogenous ethylene. Fruit obtained from plants silenced
      for either ACS (ACC synthase; ACC-1-aminocyclopropane-1-carboxylic acid) or ACO
      (ACC oxidase), key enzymes responsible for ethylene biosynthesis, expectedly
      showed reduced autocatalytic ethylene production. Ethylene suppressed fruits were
      significantly firmer than controls and displayed an increased shelf-life. No
      significant difference was observed in sugar or acid accumulation suggesting that
      sugar and acid composition and accumulation is not directly under ethylene
      control. Interestingly, a significant and dramatic suppression of the synthesis
      of volatile esters was observed in fruit silenced for ethylene. However, no
      significant suppression was observed for the aldehyde and alcohol precursors of
      these esters. Our results indicate that ethylene differentially regulates fruit
      quality components and the availability of these transgenic apple trees provides
      a unique resource to define the role of ethylene and other factors that regulate
      fruit development.

PMID- 15517997
TI  - Overexpression of GSK3betaS9A resulted in tau hyperphosphorylation and morphology
      reminiscent of pretangle-like neurons in the brain of PDGSK3beta transgenic mice.
AB  - It has been demonstrated that GSK3beta is involved in Alzheimer Disease (AD)
      pathogenesis. In order to understand the underlying mechanism, we have generated
      and characterized transgenic mice in which the constitutively active human
      GSK3beta (with S9A mutation) was overexpressed in the brain under the control of
      the platelet-derived growth factor (PDGF) B-chain promoter. Varying levels of
      human GSK3betaS9A transgene protein expression was observed in six of the seven
      founders generated. Line 3083, 3107, 3112 and 3125 displayed higher GSK3betaS9A
      protein expression levels. Immunostaining analysis demonstrated that transgene
      expression was observed mainly in cortex and hippocampus of transgenic brain.
      Expression of human GSK3beta transgene did not significantly change the brain
      total GSK3beta protein levels in any of the generated mouse lines, as comparing
      to age matched wild type mice. Although significant kinase activity was detected
      in human GSK3betaS9A transgene protein extracted from brains of all six
      expressing lines, significant increase in total GSK3betaS9A kinase activity was
      observed only in the offspring of line 3083 and 3107. By analyzing the offspring
      from several transgenic mouse lines, including lines other than 3083 and 3107, it
      was found that overexpressed constitutively active human GSK3betaS9A resulted in
      hyperphosphorylation of tau and morphology reminiscent of pretangle-like neurons
      in cortex and hippocampus.

PMID- 15517998
TI  - [Can and should Danish medical science be measured?].

PMID- 15517999
TI  - [Prohibition of suicide methods instruction].

PMID- 15518000
TI  - [Beta-blocker and calcium antagonist poisoning. Two cardiological problems with
      an endocrinological solution?].

PMID- 15518001
TI  - [Communication skills training for health care professionals working with cancer
      patients, their families and/or carers].

PMID- 15518002
TI  - [Physical exercise, an effective treatment of catabolism in skeletal muscles in
      chronic heart failure].

PMID- 15518003
TI  - [Degree of coverage of Danish health sciences research in the Science Citation
      Index, 1998].

PMID- 15518004
TI  - [Fine-needle aspiration cytology in the evaluation of head and neck tumors. What
      is the cause of inadequate samples?].

PMID- 15518005
TI  - ["Looking your age"--genetics and mortality].

PMID- 15518006
TI  - [Effect of N-acetylcysteine on prothrombin index in patients with uncomplicated
      paracetamol poisoning].

PMID- 15518007
TI  - [Hanging corner of the mouth].

PMID- 15518008
TI  - [Suicide by inhaling helium inside a plastic bag].

PMID- 15518009
TI  - [Avascular necrosis of the trochlea humeri epiphysis].

PMID- 15518010
TI  - [Concomitant arterial and venous thrombosis in a body builder with severe
      hyperhomocysteinemia and abuse of anabolic steroids].

PMID- 15518011
TI  - [Picture of the month: Mollaret meningitis].

PMID- 15518012
TI  - [Incidence of sepsis and mortality].

PMID- 15518013
TI  - [Gleam in the eye and acute eye examination].

PMID- 15518014
TI  - [When is gestational diabetes confirmed?].

PMID- 15518015
TI  - [Pityriasis rubra pilaris].

PMID- 15518016
TI  - [Is vaginal fungi hazardous for the pregnancy?].

PMID- 15518017
TI  - [Reports from the Ethics Committee are not cloned].

PMID- 15518018
TI  - [Military physicians and medical ethics].

PMID- 15518019
TI  - High rate of antimicrobial resistance in Pseudomonas aeruginosa at a tertiary
      care teaching hospital in southern Brazil.

PMID- 15518020
TI  - Gram-negative, hospital-acquired infections: a growing problem.

PMID- 15518021
TI  - Surveillance in Taiwan using molecular epidemiology for extended-spectrum beta
      lactamase-producing Klebsiella pneumoniae.
AB  - OBJECTIVE: To evaluate intrahospital and interhospital clonal dissemination of
      extended-spectrum beta-lactamase (ESBL)-producing strains of Klebsiella
      pneumoniae. SETTING: Eight tertiary-care university hospitals and 16 regional
      hospitals in Taiwan. METHODS: Two hundred eleven confirmed ESBL-producing
      isolates of K. pneumoniae were collected from January 1998 to June 2000. The
      isolates were characterized by various typing methods, including antibiogram (9
      antimicrobial agents), computer-based ribotyping, pulsed-field gel
      electrophoresis (PFGE), and isoelectric focusing of beta-lactamase. RESULTS:
      Ribotyping identified 70 distinct ribogroups among 200 isolates evaluated. Forty
      three of these ribogroups were unique. Eleven ribogroups, comprising 115
      isolates, were detected in more than one hospital (interhospital dissemination),
      whereas 16 groups (42 isolates) were detected in more than one patient within a
      hospital (intrahospital dissemination). The combination of ribotyping and PFGE
      identified two large epidemic clones, which were called 691.5/PFGE-G and
      595.7/PFGE-A. These epidemic clones were detected mainly in the hospitals located
      in the northern and central regions of Taiwan. However, variation of the profiles
      of antibiograms and isoelectric focusing was apparent within each clone. In
      addition, isolates with the same isoelectric focusing profile (isoelectric points
      7.9, 8.2, and 8.4) and antibiogram (resistance to 9 compounds evaluated) were
      present among different molecular-typed clones. CONCLUSIONS: Our results showed
      that clonal dissemination (both interhospital and intrahospital dissemination) is
      occurring in several regions of Taiwan. Rapid computer-based ribotyping
      associated with PFGE demonstrated multiple epidemic clones of ESBL-producing K.
      pneumoniae in Taiwan. The combination of phenotypic and molecular methods has
      proved useful to characterize these epidemic clones.

PMID- 15518022
TI  - Clinical features and epidemiology of Acinetobacter baumannii colonization and
      infection in Spanish hospitals.
AB  - OBJECTIVE: To investigate the clinical features and the epidemiology of
      Acinetobacter baumannii in Spanish hospitals. DESIGN: Prospective multicenter
      cohort study. SETTING: Twenty-seven general hospitals and one paraplegic center
      in Spain. METHODS: All cases of A. baumannii colonization or infection detected
      by clinical samples during November 2000 were included. Isolates were identified
      using phenotypic and genotypic methods. The molecular relatedness of the isolates
      was assessed by pulsed-field gel electrophoresis. RESULTS: Twenty-five (89%) of
      the hospitals had 221 cases (pooled rate in general hospitals, 0.39 case per
      1,000 patient-days; range, 0 to 1.17). The rate was highest in intensive care
      units (ICUs). Only 3 cases were pediatric. The mean age of the patients in the
      general hospitals was 63 years; 69% had a chronic underlying disease and 80% had
      previously received antimicrobial treatment. Fifty-three percent of the patients
      had an infection (respiratory tract, 51%; surgical site, 16%; and urinary tract,
      11%). Crude mortality was higher in infected than in colonized patients (27% vs
      10%; relative risk, 1.56; 95% confidence interval, 1.2 to 2.0; P = .003).
      Molecular analysis disclosed 79 different clones. In most hospitals, a
      predominant epidemic clone coexisted with other sporadic clones. Imipenem
      resistance was present in 39% of the hospitals. CONCLUSIONS: A. baumannii was
      present in most participating Spanish hospitals (particularly in ICUs) with
      different rates among them. The organisms mainly affected predisposed patients;
      half of them were only colonized. Epidemic and sporadic clones coexisted in many
      centers.

PMID- 15518023
TI  - Endemic multidrug-resistant Pseudomonas aeruginosa in critically ill patients.
AB  - OBJECTIVE: To describe the epidemiology of endemic multidrug-resistant
      Pseudomonas aeruginosa colonizations and infections in critically ill patients.
      DESIGN: Prospective study on bacterial strain typing and retrospective cohort
      study of charts of patients in the intensive care unit (ICU). PATIENTS: Fifty
      three patients with P. aeruginosa isolated from clinical cultures in 2001 were
      selected, divided into those with P. aeruginosa in vitro resistant to at least
      two classes of antibiotics (multidrug-resistant, n = 18) and those susceptible to
      all or resistant to only one antibiotic (susceptible, n = 35). RESULTS: Risk
      factors for multidrug-resistant P. aeruginosa included maxillary sinusitis, long
      dwelling central venous catheters, prolonged use of certain antibiotics, a high
      lung injury score, and prolonged mechanical ventilation and duration of stay. The
      frequency of colonization (approximately 50%) versus infection (ie, ventilator
      associated pneumonia) did not differ between the groups. On amplified fragment
      length polymorphism analysis, 64% of the multidrug-resistant strains had been
      potentially transmitted via cross-colonization and 36% had probably originated
      endogenously. ICU mortality was 22% in the multidrug-resistant group and 23% in
      the susceptible group, although the duration of mechanical ventilation was longer
      in the former. CONCLUSIONS: Patients with sinusitis who stayed in the ICU longer,
      were ventilated longer because of acute lung injury, received antibiotics for
      longer durations, and had long-dwelling central venous catheters ran an elevated
      risk of acquiring multidrug-resistant P. aeruginosa. These patients did not have
      a higher mortality than patients with susceptible P. aeruginosa. Prevention of
      the emergence of multidrug-resistant strains requires changes in infection
      control measures and antibiotic policies in our ICU.

PMID- 15518024
TI  - Reduced use of third-generation cephalosporins decreases the acquisition of
      extended-spectrum beta-lactamase-producing Klebsiella pneumoniae.
AB  - OBJECTIVES: To identify risk factors for the respiratory acquisition of extended
      spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae among patients
      admitted to a neurosurgical intensive care unit (NSICU) and to modify them
      without changing general infection control measures. DESIGN: Nested case-control
      and intervention study. SETTING: A 1,200-bed, tertiary-care teaching hospital
      with a 17-bed NSICU. METHODS: Sputa of all patients admitted to the NSICU were
      cultured weekly during the study. From October 2002 through February 2003, 29
      case-patients from whose sputum ESBL-producing K. pneumoniae was isolated were
      detected and 59 controls-patients were randomly selected among patients without
      any positive isolate of ESBL-producing K. pneumoniae. After analyzing the risk
      factors, we intervened to modify them and compared the acquisition rate of ESBL
      producing K. pneumoniae before (October 2002 to February 2003) and after (April
      to August 2003) the intervention. RESULTS: Multivariate analysis showed that
      prior exposure to third-generation cephalosporins (TGCs) (OR, 6.0; CI95, 1.9 to
      18.6; P = .002) was an independent risk factor of ESBL-producing K. pneumoniae
      acquisition. The neurosurgical team was notified of the result, and the
      infectious diseases specialist visited the NSICU three times a week to regulate
      TGC use during the intervention period. Patients admitted before the intervention
      were older than patients admitted after. The respiratory acquisition of ESBL
      producing K. pneumoniae per 1,000 patient-days (13.5 [CI95, 8.9 to 18.1] vs 2.7
      [CI95, 0.9 to 4.6]) and the antimicrobial use density of TGCs (38.2 +/- 5.0 vs
      17.3 +/- 2.6; P < .001) decreased significantly after the intervention.
      CONCLUSION: Prior exposure to TGCs was an independent risk factor for the
      respiratory acquisition of ESBL-producing K. pneumoniae, and less use of TGCs was
      associated with a decrease in acquisition.

PMID- 15518025
TI  - Control of Enterobacteriaceae producing extended-spectrum beta-lactamase in
      intensive care units: rectal screening may not be needed in non-epidemic
      situations.
AB  - OBJECTIVE: To evaluate the usefulness of screening cultures in the control of
      extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in intensive
      care units (ICUs). DESIGN: A 4-year retrospective study. SETTING: Two adult ICUs
      of a university-affiliated public hospital in France. RESULTS: A total of 7,777
      specimens were analyzed and 28 (0.97%) of 2,883 screened patients had a positive
      result on a screening test, among the 3,678 admitted patients. Thirteen of these
      28 patients were only carriers; 4 were carriers and then were colonized or
      infected 2, 2, 3, and 8 days later, respectively; and 11 were colonized or
      infected before a screening test was positive. Cluster analysis showed that the
      occurrence of ESBL-producing Enterobacteriaceae cross-transmission within both
      ICUs was limited to 9 cases. Thus, most cases (19 of 28) were probably imported.
      Surveillance cultures failed to detect 9 of the 19 cases. CONCLUSION: The low
      prevalence of ESBL-producing Enterobacteriaceae carriers on admission (0.45%) and
      the relative ineffectiveness of our screening test to detect imported cases
      suggest that systematic detection of ESBL-producing Enterobacteriaceae in ICU
      patients is not cost-effective and that the use of clinical cultures may be
      sufficient to control ESBL-producing Enterobacteriaceae in non-epidemic
      situations.

PMID- 15518026
TI  - Rapidly rising prevalence of nosocomial multidrug-resistant, Gram-negative
      bacilli: a 9-year surveillance study.
AB  - OBJECTIVE: To examine and quantify the temporal trends of nosocomial multidrug
      resistant, gram-negative bacilli. DESIGN: A 9-year surveillance study was
      conducted. Multidrug resistance was defined as resistance to 3 or more
      antimicrobial classes. SETTING: Tertiary-care institution. RESULTS: From 1994 to
      2002, multidrug-resistant, gram-negative bacilli increased from 1% to 16% for
      multidrug-resistant Pseudomonas aeruginosa, 4% to 13% for multidrug-resistant
      Enterobacter species, 0.5% to 17% for multidrug-resistant Klebsiella species, 0%
      to 9% for multidrug-resistant Proteus species, and 0.2% to 4% for multidrug
      resistant Escherichia coli (P < or = .05). The most common pattern of multidrug
      resistance was co-resistance to quinolones, third-generation cephalosporins, and
      aminoglycosides. CONCLUSION: The rapid rise of multidrug-resistant, gram-negative
      bacilli may warrant infection control programs to include these pathogens in
      strategies aimed at limiting the emergence and spread of antimicrobial-resistant
      pathogens.

PMID- 15518027
TI  - Evaluation of three molecular typing techniques for nonfermentative Gram-negative
      bacilli.
AB  - OBJECTIVE: To evaluate three different DNA techniques for typing nonfermentative
      gram-negative bacilli isolated from Latin American hospitals. DESIGN: One hundred
      twenty-six nonfermentative gram-negative bacilli were typed. PARTICIPANTS:
      Pseudomonas aeruginosa (n = 64) and Acinetobacter baumannii (n = 42) samples were
      obtained from blood cultures of patients admitted to 10 medical centers in Latin
      America during 1998 and Stenotrophomonas maltophilia (n = 20) samples were
      obtained from patients admitted to the Hospital Sao Paulo between 1999 and 2001.
      METHODS: All samples were typed using automated ribotyping, PFGE, and ERIC-PCR.
      The discriminatory power for each technique was calculated using Hunter's
      generalized formula. RESULTS: All strains could be typed by automated ribotyping
      and ERIC-PCR, but two strains (1.6%) were not typeable by PFGE. All three
      techniques showed 100% reproducibility. The time to obtain the results was
      shorter for automated ribotyping and ERIC-PCR compared with PFGE. Likewise, the
      costs for ERIC-PCR and PFGE were lower than those for automated ribotyping. The
      interpretation of results was more complicated and more difficult with ERIC-PCR
      than with both PFGE and automated ribotyping. All techniques presented excellent
      discriminatory power for P. aeruginosa (0.98). PFGE presented the highest
      discriminatory power (0.94) for A. baumannii, and both PFGE and ERIC-PCR showed
      higher discriminatory power (0.90 for both) than automated ribotyping (0.82) for
      S. maltophilia. CONCLUSIONS: PFGE showed the highest discriminatory power for
      typing these nonfermentative gram-negative bacilli. However, automated ribotyping
      and ERIC-PCR can provide results in a shorter time period with similar
      discriminatory power.

PMID- 15518028
TI  - Molecular epidemiology of extended-spectrum beta-lactamase-producing
      Enterobacteriaceae isolated from environmental and clinical specimens in a
      cardiac surgery intensive care unit.
AB  - OBJECTIVES: To investigate environmental contamination by extended-spectrum beta
      lactamase-producing Enterobacteriaceae and to perform a comparative molecular
      analysis of clinical and environmental strains. SETTING: A 17-bed cardiac surgery
      intensive care unit of a 480-bed university teaching hospital. METHODS: Following
      an outbreak of extended-spectrum beta-lactamase-producing Enterobacteriaceae, an
      environmental survey revealed extensive contamination of the environment
      (particularly faucets, sink drains, and the joints of the countertops) by
      extended-spectrum beta-lactamase-producing Enterobacteriaceae. Environmental
      strains were compared with clinical strains by pulsed-field gel electrophoresis
      and randomly amplified polymorphic DNA. RESULTS: A total of 62 environmental
      strains belonging to 4 species of extended-spectrum beta-lactamase-producing
      Enterobacteriaceae were analyzed and compared with 43 clinical strains obtained
      from 34 patients. Comparative molecular analysis revealed 4 identical or closely
      related patterns (3 from Klebsiella oxytoca and 1 from Enterobacter cloacae)
      between environmental and clinical strains. CONCLUSIONS: Moist surfaces may serve
      as sources of multiply resistant Enterobacteriaceae in the intensive care unit.
      Identification and disinfection of such sources may therefore be helpful in
      prevention and control of outbreaks.

PMID- 15518029
TI  - Multidrug-resistant Pseudomonas aeruginosa cholangitis after endoscopic
      retrograde cholangiopancreatography: failure of routine endoscope cultures to
      prevent an outbreak.
AB  - BACKGROUND: Nosocomial infections due to medical devices are of increasing
      concern to infection control practitioners. Attempts to prevent such infections
      have included surveillance cultures of endoscopes and bronchoscopes. In July
      2002, the infectious disease consultation service was asked to see three patients
      with sepsis due to multidrug-resistant Pseudomonas aeruginosa after endoscopic
      retrograde cholangiopancreatography (ERCP). OBJECTIVE: To describe an outbreak of
      multidrug-resistant P. aeruginosa sepsis after ERCP at an institution that
      performs routine surveillance cultures of endoscopes. DESIGN: A traditional
      outbreak investigation supplemented by pulsed-field gel electrophoresis (PFGE)
      was undertaken, including a case-control analysis based on the hypothesis that
      all infected individuals had their ERCP performed with the same endoscope.
      SETTING: A tertiary-care academic medical center. RESULTS: The case-control
      analysis confirmed the hypothesis that undergoing ERCP with the implicated
      endoscope was associated with a culture positive for Pseudomonas (P = .01). The
      available strains were identical by PFGE. This outbreak occurred despite a
      negative surveillance culture of the implicated endoscope 1 month earlier.
      CONCLUSIONS: Infectious morbidity can occur after endoscopy despite negative
      surveillance cultures. The practice of routine endoscope cultures does not
      prevent device-related infectious morbidity.

PMID- 15518030
TI  - Risk factors for and clinical outcomes of bloodstream infections caused by
      extended-spectrum beta-lactamase-producing Klebsiella pneumoniae.
AB  - OBJECTIVE: To evaluate risk factors and treatment outcomes of bloodstream
      infections caused by extended-spectrum beta-lactamase-producing Klebsiella
      pneumoniae (ESBL-KP). DESIGN: Retrospective case-control study. Stored blood
      isolates of K. pneumoniae were tested for ESBL production by NCCLS guidelines,
      double-disk synergy test, or both. SETTING: A 1,500-bed, tertiary-care university
      hospital and referral center. PATIENTS: Sixty case-patients with bacteremia due
      to ESB-KP were compared with 60 matched control-patients with non-ESBL-KP.
      RESULTS: There were no significant differences in age, gender, APACHE II score,
      or underlying diseases between the groups. Independent risk factors for
      infections caused by ESBL-KP were urinary catheterization, invasive procedure
      within the previous 72 hours, and an increasing number of antibiotics
      administered within the previous 30 days. Complete response rate, evaluated 72
      hours after initial antimicrobial therapy, was higher among control-patients
      (13.3% vs 36.7%; P = .003). Treatment failure rate was higher among case-patients
      (35.0% vs 15%; P = .011). Overall 30-day mortality rate was 30% for case-patients
      and 28.3% for control-patients (P = .841). Case-patients who received imipenem or
      ciprofloxacin as a definitive antibiotic had 10.5% mortality. The mortality rate
      for initially ineffective therapy was no higher than that for initially effective
      therapy (9.1% vs 11.1%; P = 1.000), but statistical power was low for evaluating
      mortality in the absence of septic shock. CONCLUSION: For K. pneumoniae
      bacteremia, patients with ESBL-KP had a higher initial treatment failure rate but
      did not have higher mortality if antimicrobial therapy was appropriately adjusted
      in this study with limited statistical power.

PMID- 15518031
TI  - Emergence of resistance in Pseudomonas aeruginosa and Acinetobacter species after
      the use of antimicrobials for burned patients.
AB  - OBJECTIVES: To evaluate the emergence of resistance of Pseudomonas aeruginosa and
      Acinetobacter species to imipenem, ciprofloxacin, or both after the use of these
      drugs and to compare resistant with susceptible isolates by molecular typing.
      DESIGN: Cohort study. SETTING: Burn intensive care unit (ICU) with 4 beds in a
      tertiary-care university hospital. METHODS: During 16 months, surveillance
      cultures were performed for all patients admitted to the ICU. Demographic
      information was obtained for each patient. Molecular typing was done by pulsed
      field gel electrophoresis using restriction enzymes for 71 isolates of P.
      aeruginosa and Acinetobacter species. RESULTS: Thirty-four patients were admitted
      and 22 were colonized by susceptible P. aeruginosa or Acinetobacter species
      before they used the antimicrobials. Nine (41%) of these patients had a resistant
      isolate after antimicrobial use: 5 had used imipenem alone, 1 had used
      ciprofloxacin, and 3 had used both drugs. The interval between isolation of the
      susceptible and resistant isolates ranged from 4 to 25 days, but was 10 or more
      days for 6 patients. Molecular typing revealed that susceptible and resistant
      isolates from each patient were different and that although there were no
      predominant clones among susceptible isolates, there was a predominant clone
      among resistant isolates of P. aeruginosa and of Acinetobacter. CONCLUSIONS:
      Resistance was not due to the acquisition of resistance mechanisms by a
      previously susceptible strain, but rather to cross-transmission. Although various
      measures involving antimicrobial use have received great attention, it would seem
      that practices to prevent cross-transmission are more important in controlling
      resistance.

PMID- 15518032
TI  - Incidence of urinary tract infection following transrectal ultrasound guided
      prostate biopsy at a tertiary-care medical center in Lebanon.
AB  - OBJECTIVE: To determine the incidence of urinary tract infections (UTIs)
      following transrectal ultrasound guided needle biopsy of the prostate (TRUBP) and
      the bacteriology of these infections. DESIGN: Retrospective evaluation of the
      charts and records of all patients who underwent TRUBP between June 1, 2002, and
      August 31, 2003. SETTING: American University of Beirut Medical Center, a
      tertiary-care center in Lebanon. PATIENTS: Two hundred seven patients underwent
      TRUBP. All received prophylactic antibiotics. One hundred twenty (58%) received
      ciprofloxacin alone, whereas 87 (42%) received both ciprofloxacin and gentamicin.
      Sixty-one patients (29.5%) had an enema prior to the procedure, whereas 146
      (70.5%) did not. RESULTS: Thirteen patients (6.3%) were admitted with UTI. All
      had rigors and fever on admission. Symptoms appeared at a mean of 2.7 days and
      the mean hospital stay was 9.2 days. The mean duration of antibiotic treatment
      was 23.2 days. Ten (77%) of the patients had positive bacteriology. Urine
      cultures were positive in 8 (61.5%) of the patients and blood cultures in 6
      (46.2%). All positive cultures grew Escherichia coli resistant to ciprofloxacin,
      with 5 isolates producing extended-spectrum betalactamases. CONCLUSIONS: TRUBP
      continues to be associated with significant infectious complications, especially
      UTI. Given the increasing incidence of antibiotic resistance mainly among the
      Enterobacteriaceae, antimicrobial prophylaxis practices should be reevaluated and
      the universal administration of quinolones alone or in combination with
      aminoglycosides should be reconsidered.

PMID- 15518033
TI  - A cluster of nosocomial Klebsiella oxytoca bloodstream infections in a university
      hospital.
AB  - BACKGROUND: On February 19, 2003, four patients (patients 1-4) in the neurology
      ward underwent cranial magnetic resonance angiography (MRA) and developed fever
      within 1 hour afterward. Klebsiella oxytoca was isolated from blood cultures of
      patients 1 through 3. OBJECTIVE: To identify the source of this cluster of
      nosocomial K. oxytoca bloodstream infections. DESIGN: Outbreak investigation.
      SETTING: A 1,000-bed university hospital. METHODS: The infection control team
      reviewed patient charts and interviewed nursing staff about the preparation and
      administration of parenteral fluids. The procedure of cranial MRA was observed.
      Arbitrarily primed polymerase chain reaction (AP-PCR) was performed to show the
      clonal relationship among these three strains. RESULTS: AP-PCR revealed that
      three K. oxytoca isolates had the same molecular profile. Cranial MRA was found
      to be the only common source among these patients. During MRA, before injection
      of the contrast medium, normal saline solution was infused to check the
      functioning of the intravenous catheter. Use of the solution for multiple
      patients was routine, but the access diaphragm of the bottle was not cleansed.
      The bottle of normal saline solution used on February 19 had already been
      discarded and the culture sample taken from the solution on the day of
      observation was sterile. CONCLUSIONS: We speculate that normal saline solution
      became contaminated during manipulation and that successive uses might have been
      responsible for this cluster. Poor aseptic techniques employed during successive
      uses appear to be the most likely route of contamination. Use of parenteral
      solutions for multiple patients was discontinued.

PMID- 15518034
TI  - Intrinsic Klebsiella pneumoniae contamination of liquid germicidal hand soap
      containing chlorhexidine.
AB  - We describe intrinsic contamination with Klebsiella pneumoniae occurring during
      the manufacture of germicidal hand soap, labeled as containing 2% chlorhexidine,
      used throughout a 350-bed community medical center. A 3-year retrospective study
      failed to find evidence of increased incidence of clinical isolates of this
      strain.

PMID- 15518035
TI  - Molecular typing of Agrobacterium species isolates from catheter-related
      bloodstream infections.
AB  - Agrobacterium isolates from intravenous catheters of three hospitalized patients
      were initially identified as A. tumefaciens, but inability to produce 3
      ketolactose revealed that two of them were A. vitis. However, rDNA analysis
      correlated all of the isolates to A. tumefaciens. Pulsed-field gel
      electrophoresis analysis ascertained the nosocomial transmission of the
      infection.

PMID- 15518036
TI  - Principles of autoantibodies as disease-specific markers.

PMID- 15518037
TI  - Validation of autoantibody assays in type 1 diabetes: workshop programme.

PMID- 15518038
TI  - The biostatistics of prediction.

PMID- 15518039
TI  - The women's health initiative: a potential resource for future studies of
      autoimmune diseases.
AB  - The women's health initiative observational and clinical trials cohort is one of
      the largest and most carefully characterized group of postmenopausal women who
      have undergone long-term follow-up. Although outcome assessment has focused on
      the outcomes of CVD, cancer, and fractures, a wealth of data have been collected,
      which could form the basis for researchers interested in autoimmune diseases to
      begin important studies. Baseline and follow-up blood samples and DNA samples are
      available upon application to the study's Design and Analysis Committee and
      publications can be planned based on the current dataset upon application to the
      Publications and Presentations Committee. In both of these cases, one of the
      principal investigators from the 40 clinical centers or the Central Coordinating
      Center would need to be involved as a collaborator. Upon obtaining appropriate
      IRB approval, it could be possible to recontact women to collect additional
      information to verify outcomes or obtain further follow-up data. In addition to
      the WHI, the National Institutes of Health have funded a number of other large
      cohort studies that could be of use for researchers of autoimmune diseases. These
      include several longitudinal studies of diabetes funded by the NIDDK and several
      other large cardiovascular cohorts funded by the National Heart, Blood and Lung
      institute (e.g. ARIC, CARDIA and CHS. In addition, the national Cancer Institute
      has funded studies of large cohorts of Whites, Blacks, Hispanics, and American
      Indians in the United States. In all these studies, individuals have undergone
      baseline assessment for environmental and lifestyle risk factors and are being
      followed for long-term health outcomes. Given the time and expense devoted to the
      Women's Health initiative and these other studies, it would be of great value if
      researchers interested in a wide variety of chronic diseases would make use of
      these rich sources of data.

PMID- 15518040
TI  - High-throughput methods for measuring autoantibodies in systemic lupus
      erythematosus and other autoimmune diseases.
AB  - Numerous groups have now validated high-throughput approaches to autoantibody
      profiling in a variety of systems. Recently, we have used autoantigen microarray
      technology to identify distinct autoantibody profiles in H-2 congenic MRL/lpr
      mice (Sekine et al., manuscript in preparation), and we are expanding this
      platform to study human and mouse models of IDDM and RA. We are also developing
      protein arrays for multiplex analysis of serum antibody isotypes. Multiplexed
      methods for autoantibody profiling will undoubtedly continue to uncover novel
      aspects of autoimmunity and B cell biology. It is now time to move these
      technologies beyond the proof-of-concept phase, and start addressing the next
      series of important questions. These include, but certainly are not limited to:
      identifying "autoantibody signatures" associated with disease state or outcome;
      profiling autoantibodies during the natural course of murine and human disease;
      and monitoring changes in autoantibody profiles of patients in response to
      therapeutic intervention. However, the next set of challenges is just right
      around the corner. As data and statistical analysis tools become more robust, it
      will be possible to generate and approach new hypotheses at an unprecedented
      pace.

PMID- 15518041
TI  - IP-10 and type 1 diabetes: a question of time and location.
AB  - Chemokines are key signal molecules that attract cells of the host immune system
      to the site of a potential threat. Virus infections usually induce a massive
      chemokine and cytokine burst and therefore recruit a large plethora of leukocytes
      to the site of infection with the goal to restrict and abrogate viral spread. The
      down side of this massive excitation of the human defense system is non-specific
      activation of potentially self-reactive lymphocytes. Coupled with an antigen
      specific event, for example molecular mimicry between host components and viral
      proteins, autoimmunity might be the consequence in susceptible individuals.
      However, activated immune components with autoaggressive potential must find
      their target and must remain in one site sufficiently long in order to cause
      chronic tissue damage. In this review we will focus on the influence of the
      chemokine IP-10 (CXCL10) on the trafficking of autoaggressive cells during the
      immunopathogenesis of type 1 diabetes (T1D) and explain why IP-10 can have a dual
      effect on T1D depending on time and location of expression.

PMID- 15518042
TI  - Humoral autoimmunity in pemphigus.

PMID- 15518043
TI  - Autoantibodies as diagnostic and predictive markers of vitiligo.

PMID- 15518045
TI  - Autoantibodies to citrullinated (poly)peptides: a key diagnostic and prognostic
      marker for rheumatoid arthritis.

PMID- 15518046
TI  - Systemic lupus erythematosus and related diseases.

PMID- 15518044
TI  - Autoantibodies as predictive and diagnostic markers of idiopathic inflammatory
      myopathies.

PMID- 15518047
TI  - Sjogren's syndrome.

PMID- 15518048
TI  - Antiphospholipid (Hughes) syndrome.

PMID- 15518049
TI  - Wegener's granulomatosis.

PMID- 15518050
TI  - Myasthenia gravis.

PMID- 15518051
TI  - Multiple sclerosis.

PMID- 15518052
TI  - Primary biliary cirrhosis.

PMID- 15518053
TI  - Autoimmune hepatitis and sclerosing cholangitis.

PMID- 15518054
TI  - Addison's disease.

PMID- 15518055
TI  - Autoimmune thyroid disease.

PMID- 15518056
TI  - Type 1 diabetes as a model for prediction and diagnosis.

PMID- 15518057
TI  - Cardiomyopathies.

PMID- 15518058
TI  - Atherosclerosis.

PMID- 15518059
TI  - Pernicious anaemia.

PMID- 15518060
TI  - Autoimmune thrombocytopenias.

PMID- 15518061
TI  - [Facial skeleton traumas in farmers in east-central region of Poland (part I)].
AB  - On the base of medical documentation, we presented epidemiological analysis of
      215 patients treated for traumas of facial skeleton, which occurred during
      agricultural tasks. It was concluded that the injuries mentioned above occurred
      more frequently in males at the age between 18-40. The traumas in this group
      occurred mainly during use of jig saw or other tools and machinery used in
      agriculture. However in the female population injuries of facial skeleton
      resulted mainly from zoogenous trauma and accidental fall downs.

PMID- 15518062
TI  - [Outcome assessment of kidney transplantation in Katowice in years 1983-2000].
AB  - The aim of this study was to analyze the 20 years experience of the Renal
      Transplantation Center in Katowice in which 681 kidney transplants in 678
      patients were performed between March 1983 and December 2000. Several parameters
      have been analyzed in this group: HLA class I and class II antigens
      compatibility, the mean cold ischaemia time, time to restore renal function,
      recipient's mortality, the causes of recipients' death, the early post-transplant
      complications, and patients' and grafts' survival. In the analyzed period of time
      HLA matching improved significantly (the median number of matched antigens of
      class I and II increased from 1 to 3) and the mean cold ischaemia time decreased
      from 27 to 20 hours. The number of transplants with early graft function
      increased from 9.5 to 42% and the number of primary non-functioning grafts
      decreased from 16 to 9%. Also recipients' early mortality declined significantly
      (from 31 to 5.5%). Among early post-transplant complications cases with sepsis
      and gastrointestinal bleeding decreased significantly. Improvement of both one
      year and five-years graft survival was observed. During the observation period
      the number of donors did not changed and the rate of living kidney donors
      remained very low (1.76% of all transplants).

PMID- 15518063
TI  - [Quality of life in women after mastectomy].
AB  - The aim of the study was evaluation of quality of life of women after radical
      mastectomy. It was assumed that cancer of the breast, treatment and results could
      cause the decrease of quality of life. 107 women aged from 40 to 75 years after
      radical mastectomy were examined. Questionnaire made by G. Hansen at Norwegian
      University of Sport and Physical Education was used in all women. Questionnaire
      consists of 4 parts and contains 87 questions concerning general and medical
      data, quality of life and physical activity. Examined women had not any problems
      in daily activity. Most of them (about 70%) had difficulty in physical effort,
      particularly using upper extremities. 60% of women did not work, but they had a
      hobby (about 70%). Housework and daily activity were less efficient in 80% women
      after radical mastectomy. We observed a change in psychical status of examined
      women. They had some problems with concentration, irritation, irritability and
      sleep. These problems did not influence the family relationships and contacts
      with other people. Instead we noticed change in self-rating of women after
      radical mastectomy. Removal of breast--attribute of femininity--changed
      sexuality, consciousness of femininity and appearance of an image. We observed
      "half woman complex" in examined women. Women evaluated status of their body and
      quality of life from 3 to 5 in 7-gradual scale.

PMID- 15518064
TI  - [Comparison of immunogenicity and safety of Engerix B and Twinrix vaccine].
AB  - The objective of the study was to compare the immunogenicity and the safety
      profile of Engerix B and Twinrix vaccines. 72 people were qualified for the
      vaccination, including 41 women (average age 41.2) and 31 men (average age 44.8).
      The subjects were divided into two groups: Group I--vaccinated with Engerix B (37
      persons) and Group II--vaccinated with Twinrix (35 persons). The vaccines were
      prepared and administered according to the recommended vaccination scheme: 0-1-6
      months. 30 days after the last vaccine dose, qualitative and quantitative tests
      were performed for antibodies anti-HBs (Group I and II) and anti-HAV (Group II).
      Also, the occurrence of local and general adverse events after vaccinations was
      observed--on the vaccination day and during 3 consecutive days. In Group I,
      presence of anti-HBs antibodies was observed in 35 persons, not observed in 2
      persons, while in Group II, anti-HBs antibodies were found in 34 persons, while
      in 1 person no such antibodies were stated. Anti-HAV antibodies were observed in
      33 persons from Group II. The anti-HBs antibodies titres did not show significant
      statistical differences in the groups studied, except for the range 500-1000 IU/l
      (3 persons in Group I, lack in Group II) and 1000-5000 IU/l (2 persons in Group
      I, lack in Group II). Local side effects (redness, pain at the injection site,
      swelling) and general adverse events (fatigue, headache, temperature > 37.5
      degrees C) were rare and disappeared within the 4-day observation period. The
      results achieved are a good recommendation for the vaccines studied, suggesting
      that vaccination with them are a safe and efficient form of prophylaxis against
      viral hepatitis.

PMID- 15518065
TI  - [Use of preventive strategies by surgeons and HIV exposure].
AB  - The objective of this study was to estimate how often surgeons use surgical
      gowns, masks, gloves and eyewear in the context of occupational exposure to HIV.
      The authors also wanted to determine what factors were associated with the use of
      these strategies. Generally surgeons reported infrequent use of preventive
      strategies. Regular use of double gloving was reported only by 8.5% of
      respondents, eye protection by 23%. About three-quarters of surgeons reported
      they always used masks and gowns, 86%--single gloves. Doctors who used eye
      protection regularly had less blood contacts via conjunctiva per year than
      surgeons who used such protection seldom or never (mean = 17.6 SD 52.2 vs mean =
      21.5 SD 73.6; p<0.003). The older surgeons were more likely than the other
      respondents to use preventive strategies (p<0.01). Also, the orthopaedic surgeons
      more than the others adopted such strategies (p<0.0007). To improve the
      situation, efforts will need to be done to motivate the surgeons to adopt
      preventive strategies through adequate education system. Improving the comfort of
      barrier precautions and making them available may also increase the compliance
      with protection against HIV in the operation room.

PMID- 15518066
TI  - [Comparative evaluation of two health-related quality of life questionnaires in
      patients with sleep apnea].
AB  - Symptoms and complications of the obstructive sleep apnea (SAS) lead to a
      significant impairment of the health-related quality of life (HRQOL) of the
      affected individuals. Most HRQOL questionnaires have been published in English.
      Formal process of evaluation has to precede the introduction of a new language
      version of a HRQOL questionnaire. We conducted a comparative evaluation of the
      Polish versions of two HRQOL questionnaires: The Calgary Sleep Apnea Quality of
      Life Questionnaire (SAQLI) and The Functional Outcomes of Sleep Questionnaire
      (FOSQ). We examined the reliability, validity, stability and responsiveness of
      both questionnaires. Cronbach's alpha coefficient amounted to 0.94 for both
      questionnaires, which confirmed their reliability. Scores of both questionnaires
      highly correlated with measures of daily sleepiness, general health and SF-36
      questionnaire scores. Both SAQLI and FOSQ gave stable results, but SAQLI was
      found to be more sensitive than FOSQ. The Polish version of FOSQ was proved to be
      a useful tool in cross-sectional assessment of HRQOL in patients with SAS.
      Stability and responsiveness of the Polish version of SAQLI and normal
      distribution of its scores make this questionnaire a preferable instrument in
      repeated assessments of HRQOL in the same group of patients.

PMID- 15518067
TI  - [Quantitative analysis of sigma genes expression in Mycobacterium tuberculosis
      cultures exposed to rifampicin and isoniazid].
AB  - The aim of the study was quantitative analysis of five genes encoding
      Mycobacterium tuberculosis sigma factors sigA, sigE, sigF, sigH, and sigI as well
      as the 85B reference gene known as the mycobacterial viability marker, in
      cultures exposed to rifampicin and isoniazid. The mRN levels were assessed using
      QRT-PCR technique, in the automated system of real time quantification with the
      ABI PRISM 7700 Sequence Detector System (TaqMan). The number of each analyzed
      gene transcript copies was expressed as a number of mRNA per 1 eg of isolated
      total RNA. In cultures exposed to the tested chemicals the number of 85B mRNA
      copies declined as compared to the controls (without tested chemicals). There was
      no detectable expression of sigA and sigI in the control cultures. Both,
      rifampicin and isoniazid induced expression of sigA and sigI genes. The sigE gene
      expression increased during exposure to isoniazid and decreased under rifampicin
      exposure conditions. The sigF mRNA was detected neither in the control culture,
      nor in cultures exposed to rifampicin or isoniazid. Both tested chemicals caused
      decrease of sigH expression.

PMID- 15518068
TI  - [Primary suture following the bile duct exploration in cholelithiasis].
AB  - Classical performance of bile duct exploration is always strictly connected with
      the problem of an incised bile duct closure. In majority of surgical centers an
      external T-tube drainage was carried out in last century. But is an external
      drainage the best method to be used? The aim of the paper was to establish
      criteria for including (or excluding) patients to groups undergoing primary
      suture of bile duct. The comparison of the patients in whom bile duct exploration
      was followed by primary suture with the group in which T-tube was left in bile
      duct lumen was performed. Recently in our Department a classical method has been
      used to operate on 65 patients with cholelithiasis. In 42 patients a
      preoperatively planned bile duct exploration has been performed. In 14 patients a
      T-tube was left after the exploration, in 24 patients bile duct was closed with a
      primary suture. In other 18 patients with residual and recurrent bile duct stones
      T-tube was left in bile duct only in two patients. Based on literature analysis,
      our observations, and surgical experience criteria for including and excluding
      patients for primary suture of bile duct have been established. Groups of
      patients with and without T-tube were compared, considering complications and
      economic aspects of hospitalization. Our opinion is that whenever in specialized
      surgical centers detailed criteria are established and followed precisely,
      primary bile duct closure is a simple and safe procedure, responsible for few
      complications. The cost of hospitalization in the case of primary suture is half
      as much as the price of the hospitalization in the case of T-tube.

PMID- 15518069
TI  - [Laparoscopic operations of incarcerated inguinal and femoral hernias].
AB  - In the years 1999-2001 625 cases of inguinal and femoral hernias were operated
      on, among them 538 (86%) laparoscopically. 21 (3.4%) emergency cases of
      incarcerated hernias were operated, among them 12 laparoscopically (2.3%). In one
      case the intestine was opened in the course of reposition. Necrotic part of the
      intestine was also resected laparoscopically. In the remaining cases the
      resection of the incarcerated organ was not necessary. The author presents the
      optimal technique in the cases of necessary intestine resection. In these cases
      after hernia operation it is suggested to exteriorize through minilaparoscopy
      necrotic part of the intestine and resect it. Moreover, small femoral hernias can
      be treated by suturing the ring of hernia.

PMID- 15518070
TI  - [Zinc status in ex-intravenous drug users infected by HIV, without clinical
      presentation of AIDS].
AB  - We prospectively studied the serum zinc status and development of HIV infection
      in HIV infected ex-intravenous drug users (IDUS). It was prospective study of 75
      persons (53 HIV infected persons, 22 controls). All patients in this group were
      observed and examined at baseline and every 3 months. We performed clinical
      examinations and completed blood counts, chemistry blood examinations, serum zinc
      level, LCD4 cells count. We found lower serum zinc level in HIV infected patients
      in comparison with control group. There was no significant difference among serum
      zinc level in male HIV positive patients in comparison with female HIV positive
      patients and in HIV infected patients with liver disease and in HIV infected
      patients without liver disease. In subgroups divided according to the degree of
      immunity deficiency (according to CDC classification) we do not show
      characteristic statistical differences in serum zinc level in comparison with
      control group.

PMID- 15518071
TI  - [The role of HMG-CoA reductase inhibitors in regulation of the inflammatory
      processes].
AB  - Statins operate through inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A (HMG
      CoA) reductase, a key enzyme which regulates intracellular cholesterol synthesis.
      Their so-called pleiotropic effects incorporate alterations of endothelial
      function, inflammation, coagulation and plaque stability. This review will focus
      on statins regulation role in inflammation.

PMID- 15518072
TI  - [Anorexia nervosa--diagnostic and therapeutic suggestions].
AB  - Diagnostic and therapeutic suggestions concerning anorexia nervosa including a
      wide variety of favourable conditions for its occurrence are presented based on
      the literature data.

PMID- 15518073
TI  - [The use of continuous subcutaneous insulin infusion (CSII) with personal insulin
      pumps in the treatment of children and adolescents with diabetes type 1].
AB  - This paper sums up recently published researches on the continuous subcutaneous
      insulin infusion (CSII) with the use of insulin pump in children and adolescents
      with diabetes type 1. Obtaining a balance in the organism metabolism in childhood
      and adolescence diabetology is nowadays one of the most important rules of the
      diabetes management in children. One of the modern ways to achieve that goal is
      the intensive insulin therapy model with use of the insulin pump. In this paper
      the advantages and disadvantages as well as the indications and contraindications
      for the CSII in children and adolescents with diabetes are widely discussed.

PMID- 15518074
TI  - [Contemporary opinions on the clinical symptoms, diagnosis and treatment of
      primary HIV infection].
AB  - Primary HIV infection (PHI) includes period between HIV infection and occurrence
      of anti-HIV antibodies. It is characterized by a high viral load, transient
      decrease of CD4+ T cell count, high infectivity and, what is very important, lack
      of anti-HIV antibodies. During PHI acute retroviral disease may occur with a lot
      of non-characteristic symptoms. The patients (pts) visit general practitioners
      and influenza-like infections or other viral infections are recognized. The
      additional reason of lack of proper diagnosis and the delay in diagnosis of HIV
      infection is negative result of anti-HIV antibodies. That is why the HIV
      infection is usually diagnosed very late. Patients unconscious of their HIV
      infection may be a source of infection for other people. Opinions concerning
      management of PHI are different and are discussed in the paper. The purpose of
      the paper was to present the problem of primary HIV infection to the doctors of
      different specialties, who should think about PHI in pts with risky behaviours
      for HIV infection or presenting symptoms resembling acute retroviral disease.

PMID- 15518075
TI  - [Electrophysiology in optic neuropathy].
AB  - The aim of this work is to present current state of knowledge on the subject of
      electrophysiological diagnostic methods in optic neuropathy. To evaluate optic
      nerve function we can use pattern and flash visual evoked cortical potentials
      (VEPs) and pattern electroretinography (ERG). Each method is specific and
      sensitive in other cases of impairment of the optic nerve (neuritis, toxic,
      hereditary, entrapment and ischemic neuropathy). Extensive electrophysiological
      examination including modern techniques can help in the precise diagnosis, the
      proper treatment and controlling of the effect of therapy.

PMID- 15518076
TI  - [Relations between psyche and soma in coronary disease].
AB  - The authors of the paper have presented the relations between psyche and soma on
      the example of coronary disease ranging from the elements of Plato's philosophy
      to the results of the latest studies. Various aspects of the interdependences
      between psychiatric status and somatic ailments have been discussed, biological
      factors as well as psychological ones. The necessity of the interdisciplinary,
      holistic approach to the patient has been emphasized that is a great challenge
      both to the psychiatrist and other specialists.

PMID- 15518077
TI  - [Radionuclide therapy for painful bone metastases].
AB  - The paper presents the possibilities of therapy of painful bone metastases, which
      result from nuclear medicine development. Authors discuss fundamental problems
      connected with radionuclide therapy. The emphasis is put on the efficiency and
      safety of this treatment for patients and their environment.

PMID- 15518078
TI  - [Abnormal reaction for anaesthetics in a critically ill child with acute myeloid
      leukemia--case report].
AB  - The authors present a case report of an abnormal reaction for anaesthetics
      correlated with cytostatic therapy in the course of preparation time for bone
      marrow transplantation due to acute myeloid leukemia. Problems of pharmacological
      interaction of ketamine and benzodiazepines are emphasized. Special attention was
      paid to the risk of abnormal drug reactions during general anaesthesia in
      children with leukemia.

PMID- 15518079
TI  - [Secondary primary, bilocal sigmoid colon adenocarcinoma in a patient previously
      treated for testicular cancer].
AB  - Frequency of neoplastic diseases among patients cured successfully from
      testicular cancer is higher than in normal population. Synchronous occurrence of
      neoplasms in those patients is a rarity. The case of simultaneous adenocarcinoma
      of ascending and sigmoid colon in a man effectively treated before for testicular
      cancer is presented. The patient underwent nearly total colectomy and resection
      of the rectal polyp. Six months after operation patient did not present any
      features of neoplastic disease. This case is an illustration of the problem of
      cancerogenesis within polyps of the large bowel in patients treated before by
      chemotherapy because of testicular cancer.

PMID- 15518080
TI  - [ECT treatment of Cotard's syndrome in a patient with combined valvular heart
      disease and persistent atrial fibrillation].
AB  - The case of 67-year-old woman suffering from severe depression with Cotard's
      syndrome or nihilistic delusions is presented. Refusal of drug intake, high
      suicidal risk and severe cardiologic diseases made the treatment by using
      antidepressive drugs impossible. Electroconvulsive therapy was introduced causing
      fast remission of depressive symptoms not evoking somatic side effects.

PMID- 15518081
TI  - [Abdominal Spigelian hernia].
AB  - Hernia in Spigel's semilunar line is a rare, diagnostic difficult type of
      abdominal external hernia at all. Case report of female patient aged 50-years
      treated surgically because of untypical situated (upon the navel) Spigelian
      hernia was described. The woman complained of painful left epigastrium with
      periodically revealed orange-like-tumor. Spigelian hernia was operated in general
      anaesthesia. Postoperative period was uncomplemented.

PMID- 15518082
TI  - [Proceedings of the 22nd Lung Workshop--Environment--Occupational medicine, March
      2002].

PMID- 15518083
TI  - [Future prospects of occupational medicine in Austria].

PMID- 15518084
TI  - [The status of occupational medicine in pneumology].

PMID- 15518085
TI  - [Suspended particulates and lung health].
AB  - Based on several severe air pollution episodes, a temporal correlation between
      high concentrations of particulate matter (PM) and SO2 pollution and acute
      increases in respiratory and cardiopulmonary mortality had been established in
      Vienna for the 1970's. After air pollution had decreased in Austria in the 1980's
      -as documented by data on SO2, and total suspended particles (TSP)--no such
      associations between day-to-day changes of SO2 and TSP and mortality have been
      documented any more, however, traffic related pollutants like fine particles and
      NO2 remained a problem. Therefore, short term effects of PM on lung function,
      morbidity and mortality were investigated in Vienna, Linz, Graz and a rural
      control area. Long-term exposure and chronic disease--even more important for
      public health--were studied in repeated cross-sectional, a mixed longitudinal and
      a birth cohort study on school children in the city of Linz. Lung function growth
      was found impaired from long-term exposure to air pollutants and improved in
      districts where ambient air pollution had decreased. Where only TSP and SO2 had
      decreased, no continuous improvement of small airway function was found and end
      expiratory flow rates stayed impaired where NO2-reduction from technical
      improvements of cars and industry was counterbalanced by increase of motorized
      (diesel) traffic. Remaining acute effects of ambient air pollution in 2001 from
      PM, NO2 and co-pollutants found in a time series study also show that continuing
      efforts are necessary. Active surface of particles inhaled several hours to days
      before spirometry was found related to short-term reductions in forced vital
      capacity-FVC (p<0.01), forced expiratory volume in one second-FEV1 (p<0.01) and
      maximal expiratory flow rate at 50% of vital capacity-MEF50 (p<0.05). In pupils
      with asthma or previous airway obstruction 4-week-diaries proved that the
      following symptoms increased with acute exposure to higher active surface of
      particles: wheezing (p<0.01), dyspnea, cough when going to sleep, cough at night
      (p<0.05). Efforts to reduce exposure to fine particles from motor traffic and
      passive smoking have to be increased if we want to achieve full recovery of
      children from air pollution effects and best respiratory performance in
      adulthood. Surveillance seems to be necessary not only for particle mass but also
      for particle number and surface. Little is known on the mechanisms of
      irreversible long-term effects of PM such as myocardial infarction and cancer. In
      a prospective cohort study on 1630 dust-exposed and 1630 non dust-exposed workers
      matched for smoking we found an increase of lung cancer related to nonfibrous
      insoluble PM. Other studies were able to relate lung cancer to specific particles
      like those from diesel engines, and a large prospective study of the American
      Cancer Society was able to link lung cancer in the general population with long
      term exposure to fine particles from combustion processes. All these recent
      epidemiological findings will have consequences for occupational and ambient air
      PM standards.

PMID- 15518086
TI  - [The new German general threshold limit value for dust--pro and contra the
      adoption in Austria].
AB  - Since it has been realised that inhalation of inert dust is one of the important
      confounding variables for the development of chronic bronchitis, the threshold
      values for occupational exposure to these dusts needs to be further decreased.
      The German Commission for the Investigation of Health Hazards of Chemical
      Compounds in the Work Area (MAK-Commission) has set a new threshold (MAK-Value)
      for inert dusts (4 mg/m3 for inhalable dust, 1.5 mg/m3 for respirable dust) in
      1997. This value is much lower than the threshold values currently used world
      wide. The aim of the present article is to assess the scientific plausibility of
      the methodology (databases and statistics) used to set these new German MAK
      Values, regarding their adoption in Austria. Although we believe that it is
      substantial to lower the MAK-Value for inert dust in order to prevent the
      development of chronic bronchitis as a consequence of occupational exposure to
      inert dusts, the applied methodology used by the German MAK-Commission in 1997 to
      set the new MAK-Values does not justify the reduction of the threshold limit
      value. A carefully designed study to establish an appropriate scientific basis
      for setting a new threshold value for inert dusts in the workplace should be
      carried out. Meanwhile, at least the currently internationally applied threshold
      values should be adopted in Austria.

PMID- 15518087
TI  - [Rare pulmonary occupational diseases--importance of microanalytical
      examination].
AB  - In legal proceedings on the subject of occupational diseases concerning
      comparatively rare pneumoconioses, additional analyses such as energy dispersive
      x-ray microanalysis (EDX) and electron energy loss spectroscopy (EELS) offer
      decisive information for the pathologist in establishing causal connections
      between occupational exposure to hazardous substances, foreign particle deposits
      in lung tissue and pulmonary reaction patterns. Using the example of silver
      finisher's lung, dental technician's lung and talcosis, the connections between
      foreign particle deposits in lung tissue and granulomatous and fibrosing
      pulmonary changes are shown.

PMID- 15518088
TI  - Respiratory symptoms and bronchoalveolar lavage abnormalities in molybdenum
      exposed workers.
AB  - STUDY OBJECTIVES: To detect an adverse effect of chronic inhalative molybdenum
      trioxide (MoO3) exposure in a group of symptomatic MoO3 exposed workers.
      PARTICIPANTS: 43 inhalatively MoO3 exposed workers of a metal plant and 23 non
      exposed controls were included in this study. Among the workers, 33 suffered from
      respiratory symptoms while 10 individuals were asymptomatic. INTERVENTIONS: Chest
      x-ray, spirometry and bronchoalveolar lavage (BAL) were performed using standard
      equipment. MEASUREMENTS AND RESULTS: Neither symptomatic nor asymptomatic MoO3
      exposed workers showed firm radiological signs of interstitial lung disease. In
      lung function testing, symptomatic MoO3 exposed workers did not differ from their
      asymptomatic colleagues. Employees of the metal plant had a higher percentage of
      predicted forced expiratory volume in 1 second (FEV1 %) and a higher percentage
      of predicted forced vital capacity (FVC %) than controls (p<0.05). In BAL
      cytology, symptomatic MoO3 exposed workers showed higher percentage counts of
      lymphocytes (p < 0.001) and neutrophils (p < 0.01), and higher T4/T8 ratios (p <
      0.01) than asymptomatic MoO3 exposed workers. Furthermore symptomatic workers
      showed higher percentage counts of lymphocytes (p < 0.05) and neutrophils (p <
      0.05) than individuals of the control group. CONCLUSION: The results of BAL
      cytology in symptomatic workers may be interpreted as a MoO3 induced subclinical
      alveolitis. This may indicate an adverse effect of chronic inhalative MoO3
      exposure. It remains unclear whether symptomatic MoO3 exposed workers are at risk
      for the development of an interstitial lung disease in the future.

PMID- 15518089
TI  - [Pulmonary function results in healthy subjects breathing through external
      stenoses compared to patients with airway obstruction].
AB  - We compared body plethysmographic data, flow-volume curves during spontaneous
      breathing, P0.1 and PETCO2 in healthy subjects breathing through external
      stenoses (ES) of varying magnitude to the results in patients suffering from
      chronic obstructive pulmonary disease (COPD). Inspiratory vital capacity (IVC)
      remained unchanged by experimental airway stenoses. IVC is mainly determined by
      the end-expiratory closure of the airways, which only weakly correlates with
      airway resistance in patients. External stenoses had no effect on the
      physiological end-expiratory closure of the airways. For the other spirometric
      parameters the available force of the respiratory muscles and the degree of the
      experimental stenosis played the major role. The mouth occlusion pressure (P0.1)
      showed considerably lower variation during ES as well as in COPD patients than
      total resistance (Rt). There was no increase in intrathoracic gas volume (IGV)
      causing increased tension of the lungs and the thorax during ES. The well-known
      correlation between Rt and IGV is attributed to the end-expiratory closure of the
      airways during increased flow resistance and to "trapped air". It remains open,
      if and how the expiratory muscles act to overcome the increased resistance. With
      consideration of the underlying factors of the different lung function measures,
      the combination and the analysis of the correlation between different values may
      lead to far-reaching results in lung function testing.

PMID- 15518090
TI  - [Bronchial asthmatic disease associated with tobacco dust--an occupational lung
      disease?].
AB  - Hypersensitivity to allergens in tobacco leaf as a cause of occupational asthma
      in workers of the tobacco manufacturing industry has been reported previously. We
      describe the case of a female employee working in a tobacco plant with asthmatic
      symptoms occurring at the working place. The symptoms described by the patient
      and the strong correlation to periods at work is highly suggestive for an
      occupational disease. The diagnosis of occupational bronchial asthma is supported
      by a positive skin test and bronchial provocation test with tobacco dust.

PMID- 15518091
TI  - [Orthostatic intolerance--prevalence, diagnostic management and its significance
      for occupational medicine].
AB  - OBJECTIVE: Orthostatic intolerance (OI) is a syndrome which is characterised by
      headache, concentration difficulties, palpitation of the heart, dizziness
      associated with postural tachycardia and plasma norepinephrine concentrations
      that are disportionately high in upright posture. OI hitherto can only be
      diagnosed by a tilt table examination with high expenditure. In this paper we
      examine the reliability and validity of a questionnaire as a screening instrument
      for OI. METHODS: We studied 138 young males (mean age 21.6 years) from the
      military service. After a medical check and filling in the questionnaire, the
      participants underwent a tilt table test. The questionnaire consisted of 10 items
      registering presence and frequency of typical OI-symptoms. RESULTS: 104 probands
      showed a normal tilt table test. OI was diagnosed in 14 probands, orthostatic
      hypotension (OH) in 6 and postural orthostatic tachycardia syndrome (POTS) in 14.
      The participants with OI scored significantly higher in the questionnaire than
      the normal subjects: The mean score of the OI group was 22.6, the normal
      participants had a mean score of 3.9. Participants with POTS had a mean score of
      13.5 and subjects with OH had a mean score of 17.0. CONCLUSIONS: We were able to
      establish a short questionnaire as a reliable and valid screening instrument for
      OI. Usage of this questionnaire can simplify enormously the diagnostic management
      of patients with suspected OI.

PMID- 15518092
TI  - Results of pediatric bone-anchored hearing aid implantation.
AB  - INTRODUCTION: The bone-anchored hearing aid (BAHA) system uses an osseointegrated
      titanium implant to propagate sound directly to the inner ear through the bones
      of the skull, bypassing the impedance of the skin and subcutaneous tissues.
      Children as young as 18 months have had hearing rehabilitated with this device.
      OBJECTIVES: The goals were to evaluate the efficacy of patient selection
      criteria, the safety and effectiveness of the implantation procedure, and the
      level of patient satisfaction after BAHA implantation in children. METHODS: The
      records of all pediatric patients implanted in Edmonton were retrospectively
      reviewed. Twenty patients, who received 25 implants, with postimplantation follow
      up of 6 months or greater, were included. The average follow-up was 3 years, 7
      months. RESULTS: Of 20 original implants, 3 were lost owing to trauma, whereas 2
      failed to osseointegrate. All were successfully reimplanted. Complications
      related to the implants included three instances of skin necrosis around the
      abutment. All patients and caregivers reported greater than 95% improvement in
      patient-identified listening situations. Pure-tone averages improved from a mean
      of 49 dB for the better hearing ear preoperatively to 16 dB with the BAHA set at
      normal listening levels. CONCLUSIONS: The BAHA provides a safe and effective
      means of rehabilitation of conductive or mixed hearing loss in the pediatric
      population. Our patients report a high level of satisfaction and continued use of
      their devices.

PMID- 15518093
TI  - Smoking cessation in patients diagnosed with head and neck cancer.
AB  - OBJECTIVE: To determine patients' smoking status after the diagnosis and
      treatment of squamous cell carcinoma of the head and neck (SCCHN) and to identify
      factors associated with smoking cessation. DESIGN: Cross-sectional survey study
      conducted over a 2-year period. SETTING: Head and neck surgery clinic of an
      academic tertiary care hospital. METHODS: Two hundred thirteen consecutive
      patients diagnosed with SCCHN were interviewed to ascertain patients' smoking
      status and the incidence of smoking cessation. Information on demographics,
      tobacco and alcohol history, disease characteristics, and treatment modality was
      also collected. MAIN OUTCOME MEASURES: The rate of smoking cessation was
      evaluated, in which smoking cessation is defined as the use of no cigarettes at
      least 1 month prior to the interview. Possible predictors of smoking cessation
      were evaluated. RESULTS: One hundred twenty-five patients were found to be
      smoking at the time of diagnosis. Among these patients, 53.6% stopped smoking
      after diagnosis or during treatment. In the univariate analyses, tumour site (p =
      .01), concurrent alcohol use (p = .03), and number of attempts to quit pre- (p =
      .03) and postdiagnosis (p = .001) were found to be highly predictive of patient
      smoking cessation. Multivariable modelling showed that gender, tumour site, and
      number of attempts to quit smoking were significantly and independently related
      to smoking cessation. CONCLUSIONS: Although smoking cessation would be presumed
      to be high after cancer diagnosis, this study has identified patient subgroups in
      which postdiagnosis smoking cessation intervention programs need to be made more
      effective.

PMID- 15518094
TI  - Endoscopic electrosurgical adenoidectomy: technique and outcomes.
AB  - Recent literature has embraced the use of electrosurgery and endoscopy in
      adenoidectomy, with several published articles on the subject. The combination of
      these methods and the routine use of endoscopy have not been reported. This
      approach provides a direct-targeted route to the nasopharynx, improved
      visualization, and magnification and offers a bloodless surgical field. It allows
      improved evaluation of the adenoids with their peritubal extensions, their
      lateral and central portions, and their extension to the posterior nasal choanae
      and even in the posterior nasal fossae and evaluation of the posterior of the
      middle and inferior turbinates. It permits objective documentation of the cause
      of nasal obstruction with possible use in outcome assessment. It is also an
      effective teaching method and a motivating approach for the nursing team. Our
      approach has proved cost and time efficient in our minimally invasive surgical
      (endoscopic) operating room set-up. This article reflects the experience in a
      series of 96 consecutive patients performed during a 9-month period and discusses
      the surgical technique and patients' outcomes. The endoscope and suction cautery
      were systematically used for all adenoid surgery. Outcomes were evaluated using a
      telephone survey with a global rating questionnaire.

PMID- 15518095
TI  - Prevention of nausea and vomiting after middle ear surgery: combination of
      ondansetron and dexamethasone is the right choice.
AB  - OBJECTIVE: To determine the efficacy of a combination of ondansetron and
      dexamethasone in preventing postoperative nausea and vomiting after middle ear
      surgery compared with ondansetron alone. DESIGN: A prospective, randomized,
      double-blind study with prestudy power analysis performed to determine the sample
      size. SETTING: A tertiary teaching hospital. METHOD: One hundred patients
      undergoing tympanomastoidectomy under general anesthesia were included in the
      study. Patients in group O (n = 50) received ondansetron 4 mg and those in group
      OD (n = 50) received ondansetron 4 mg with dexamethasone 8 mg 30 minutes before
      the end of surgery. All patients were monitored for nausea score, episodes of
      vomiting, and rescue antiemetic requirement in 48 hours after surgery. The total
      number of complete responders was calculated. Patients' satisfaction at the end
      of the study period was also estimated. RESULTS: In patients receiving
      combination antiemetic (group OD), the nausea score was significantly less (p <
      .01) at 6, 12, and 24 hours after surgery. The total incidence of vomiting was
      reduced from 28% in group O to 6% in group OD. Rescue antiemetic requirement was
      significantly less (p < .01) in group OD. The number of complete responders
      significantly improved in the combination group (92% vs 62%). The patients were
      also found to be more satisfied in this group. CONCLUSION: Prophylaxis with a
      combination of ondansetron and dexamethasone decreased the incidence of nausea
      and vomiting after middle ear surgery to a minimum and improved patients'
      satisfaction significantly in the postoperative period.

PMID- 15518096
TI  - Otolaryngology manpower in Canada: a crisis in the making?
AB  - Physician manpower issues have been of interest to Canadians and government
      officials for several decades. Since the first otolaryngology manpower survey was
      completed by Dr. Percy Ireland in 1962, there have been progressive declines in
      the physician-to-population ratio across Canada from 1 in 42 000 in 1962 to
      approximately 1 in 75 000 in 2000. The expected increase in our population over
      the next decade, the cutbacks in medical school enrollment, and an aging
      population will compound this problem. The system is in crisis, and this country
      is desperately in need of more otolaryngologists.

PMID- 15518097
TI  - Influence of sinus surgery in rhinometric measurements.
AB  - The objectives of this prospective study were to clarify how well acoustic
      rhinometry (AR), computed tomography volumetry (CTV), rhinomanometry (RMM), and
      the visual analogue scale (VAS) identify changes in intranasal pathology after
      endoscopic sinus surgery in patients with chronic sinusitis. The measurements
      were performed in 44 nasal cavities of 11 patients pre- and postoperatively, 6 of
      whom underwent middle meatal antrostomy and 5 of whom underwent ethmoidectomy.
      The AR and RMM results were compared with those obtained with CTV and VAS.
      Furthermore, a favourable outcome in sinus surgery was obtained with all of the
      methods. The results showed clearly that endoscopic sinus surgery significantly
      changes the intranasal geometry and can be obtained reliably using rhinometric
      measurements. Both AR and CTV identified statistically significant (p < .05)
      volume changes in the nasal cavities. The AR and CTV results correlated generally
      well (r = .72) with each other, but wide differences were seen between the
      operative groups. Correlation in the ethmoidectomy group was very strong (r =
      .93) but weak in the middle meatal antrostomy group (r = .37). In the nasal
      function measurements, nasal obstruction decreased significantly (p < .05) after
      the surgery. The changes were clearly obtained using RMM and VAS (p < .05).
      Correlation between these methods was generally poor (r < .30), but a difference
      was again seen in the operative groups. In the ethmoidectomy group, correlation
      was moderately good (r = .55) but weak in the middle meatal antrostomy group (r =
      .29). We concluded that rhinometric methods are reliable tools for evaluation of
      operative outcome in endoscopic sinus surgery patients. Inspiratory resistance
      measured with RMM and nasal obstruction assessed with VAS appeared to measure
      separate parameters in nasal function.

PMID- 15518098
TI  - Electrosurgical adenoid ablation.
AB  - OBJECTIVE: The technique of adenoidectomy has undergone many refinements over the
      years with, most recently, the addition of electrosurgery alone as a viable
      method for removal of adenoid tissue. Several studies have suggested good
      efficacy with this method. The objective of this study is to examine the
      effectiveness of adenoidectomy by electrosurgical ablation by the following
      measures: reduction of the adenoid size, blood loss, and postoperative
      complications. DESIGN AND METHODS: In this prospective study, we reviewed
      patients who underwent electrosurgical adenoid ablation for either nasal
      obstructive symptoms or chronic otitis media with effusion requiring a second or
      greater set of pressure equalization tubes and adenoidectomy. Preoperative and
      postoperative videonasopharyngoscopy were performed and evaluated. A grading
      system for adenoid size for the endoscopic parameters was used. The amount of
      blood loss and postoperative complications were recorded. RESULTS: On
      preoperative nasopharyngoscopy, 7 of 23 children had a grade II adenoid size, 15
      of 23 had grade III adenoid pads, and 1 of 23 had grade IV adenoid size.
      Postoperative follow-up at 6 to 8 weeks revealed that 19 of 23 children showed no
      evidence of adenoid tissue. Three of 23 children had only tiny residual tissue
      that fell into grade I and one had regrowth of tissue to fit into grade III.
      Eight patients were seen at 6 months postoperatively, four of whom were followed
      up to 12 months postoperatively; all showed no evidence of regrowth of adenoid
      tissue. Average blood loss for the procedure was 2.6 cc. No postoperative
      complications (postoperative bleed, dehydration requiring hospitalization,
      infection, velopharyngeal insufficiency) were encountered. CONCLUSIONS:
      Electrosurgical adenoid ablation is a safe method with minimal intraoperative
      blood loss and postoperative complications. Follow-up at 6 to 8 weeks and up to 1
      year postoperatively suggests that it is an effective method in removing adenoid
      tissue and alleviating nasal obstruction.

PMID- 15518099
TI  - When can lateral sinus thrombosis be treated conservatively?
AB  - OBJECTIVE: The purpose of this study was to review the clinical manifestations,
      radiologic findings, and treatment modalities of our cases with lateral sinus
      thrombosis (LST). METHOD: Documents of patients with LST, diagnosed and treated
      from 1995 to 2001 in our clinic, were examined retrospectively. RESULTS: Four
      patients with the diagnosis of LST were treated during this period. Among the
      clinical manifestations of these patients, the most frequently encountered
      symptoms were earache and headache, in addition to otorrhea and hearing loss.
      Four cases had chronic otitis media, three with cholesteatoma and one with
      polyps. Delta sign was detected in three cases on computed tomography, whereas a
      suspicious image was noted in one case. This case underwent magnetic resonance
      angiography, and the diagnosis of LST was established conclusively. In two cases,
      because pus was aspirated via lateral sinus punctures performed intraoperatively,
      these sinuses were explored and obliterated following radical mastoidectomy.
      Because pus was not aspirated via punctures of the other two cases, their sinuses
      were not explored. Only radical mastoidectomy was performed surgically for these
      cases. Dual antibiotics and low-dose anticoagulant therapy were given
      concomitantly to all cases in the postoperative period. Recanalizations of the
      nonobliterated lateral sinuses were detected with Doppler ultrasonography of
      internal jugular vena at 15 days and 3 months after the termination of
      postoperative treatment. CONCLUSION: Clinical findings and radiologic techniques
      play an important role in the diagnosis of LST. In the treatment, if pus is found
      in the lateral sinuses, it is necessary to explore, clean, and obliterate them,
      whereas in cases in which the aspirates do not contain pus, mastoidectomy is
      sufficient. On the other hand, a low dose of anticoagulant can be used together
      with antibiotics in the nonobliterated lateral sinuses.

PMID- 15518100
TI  - Concha bullosa squeezer for turbinoplasty (Dogru forceps).

PMID- 15518101
TI  - Primary synovial chondromatosis of the temporomandibular joint.

PMID- 15518102
TI  - Removal of a large metallic foreign body from the base of the left skull.

PMID- 15518103
TI  - Cemento-ossifying fibroma of the maxilla.

PMID- 15518104
TI  - Endoscopic resection of isolated inverted papilloma of the sphenoid sinus.

PMID- 15518105
TI  - Cervical impalement with a windshield wiper.

PMID- 15518106
TI  - Central retinal artery occlusion following a total laryngectomy.

PMID- 15518107
TI  - Lingual nerve neurilemmoma.

PMID- 15518108
TI  - When is a conductive hearing loss not a conductive hearing loss? Causes of a
      mismatch in air-bone threshold measurements or a "pseudoconductive" hearing loss.
AB  - The otolaryngologist is sometimes faced with a patient with an apparent
      conductive hearing loss on audiometric testing who appears to have normal and
      mobile middle ear structures on ear exploration. Some causes of these
      "pseudoconductive" hearing losses can be diagnosed without resorting to surgery.
      This article reviews several possible mechanisms for this condition with
      diagnostic procedures to distinguish etiologic diseases. Conditions discussed
      include poor audiometry, functional hearing losses, "third window" causes,
      obliterated round window, abnormal inner ear connection with the cerebrospinal
      fluid space, inner ear mechanical conductive hearing loss, and apparent inner ear
      loss owing to missed middle ear pathology.

PMID- 15518113
TI  - Unique marketing tools.

PMID- 15518114
TI  - What nerve! Honing your skills in cranial nerve assessment.

PMID- 15518115
TI  - Newborn screening tests.

PMID- 15518116
TI  - Detect breast cancer early with BSE.

PMID- 15518117
TI  - Much more than a headache: migraine treatment requires broader spectrum of
      therapies.

PMID- 15518118
TI  - Alternatives to hormone therapy: a clinical guide to menopausal transition.

PMID- 15518119
TI  - The vaginal pessary: an effective yet underused tool for incontinence and
      prolapse.

PMID- 15518120
TI  - Better late than never: more women take on midlife motherhood.

PMID- 15518121
TI  - Chest pain in children and adolescents: most causes are benign.

PMID- 15518122
TI  - A few steps forward.

PMID- 15518123
TI  - [Epidemiological characteristics of urolithiasis in Okhotsk coast area in
      Hokkaido].
AB  - An epidemiological study of 422 stone-formers who visited our hospital from 1997
      to 2001 was conducted. The mean annual prevalence and incidence of both upper and
      lower urinary tract stones were higher than what was found in a nationwide
      urolithiasis survey carried out in Japan in 1995. The incidence of upper and
      lower urinary tract stones was 90.8% and 9.2%, respectively. The frequency of
      lower urinary tract stones was higher than that found in the previously mentioned
      nationwide study. The male-to-female ratio of upper and lower urinary tract
      stones was 1.68:1 and 2.25:1, respectively. The frequency in females was higher
      in this study than that found in the nationwide survey. The peak age for
      incidence of upper urinary tract stones is 50s in males and females. In the
      treatment of upper urinary tract stones, ureteroscopic lithotripsy was carried
      out more often than shock wave lithotripsy (SWL), because our hospital had no SWL
      device. Many endoscopic lithotripsy procedures were performed to treat stones
      located in the lower urinary tract. Of the upper urinary tract stones 83.7% were
      composed of calcium, the incidence of uric acid stones was high (6.6%), whereas
      the incidence of infectious stones was low (1.9%). For lower urinary tract
      stones, the frequency of infectious stones was high (52.6%). In the present
      study, the epidemiological features were as follows: high annual prevalence and
      incidence, high frequency of lower urinary tract stones, high frequency in
      females, many endoscopic treatment procedures and high frequency of uric acid
      stones in the upper urinary tract.

PMID- 15518124
TI  - [Clinical results of immunosuppressive triple therapies in living-related renal
      transplantation--a single center experience].
AB  - We reviewed the outcome of three methods employed for living-related renal
      transplantation (RTx) in our institution to assess triple immunosuppressive
      regimens. Between January 1989 and July 2003, a total of 35 living-related RTxs
      were performed at our institution. The immunosuppressive regimen given to 16
      patients (group A) was cyclosporine (CsA), steroid and azathoprine (AZ) that
      given to 9 patients (group B) was tacrolimus (TAC), steroid and AZ and that given
      9 patients (group C) was TAC, steroid and mycophenolate mofetil (MMF). Graft
      survival rate, serum creatinine, proteinuria, acute rejection, chronic allograft
      nephropathy (CAN), cytomegalovirus (CMV) infection and drug-induced nephropathy
      were investigated. There was no significant difference in graft survival rate
      among the three groups. Although serum creatinine levels (mg/dl) at 3 months post
      transplant were 1.22+/-0.37 in group A, 1.43+/-0.14 in group B, 1.30+/-0.34 in
      group C, respectively (p<0.05; A vs. B), there was no significant difference at 1
      year post-transplant. Frequency of proteinuria in groups A, B and C was 75.0,
      50.0, 25.0%, respectively (p<0.05; A vs. C). The incidences of acute rejection
      and CAN within 1 year post-transplant were, respectively, 56.3% and 43.8% in
      group A, 37.5% and 37.5% in group B; and, 25.0% and 12.5% in group C (NS). The
      incidence of drug-induced nephrotoxicity was 12.5, 50.0% and 37.5% in groups A, B
      and C, respectively (p<0.05; A vs. B). The triple immunosuppressive therapy
      including calcineurin inhibitors, especially the regime of TAC, MMF, and steroids
      decreased the frequencies of proteinuria and rejections, which deteriorated the
      long-term outcome in living-related RTxs.

PMID- 15518125
TI  - [Three dimensional conformal radiotherapy (3D-CRT) for localized prostate cancer
      under field adjustment with implanted gold markers: early clinical outcome].
AB  - Three dimensional conformal radiotherapy (3D-CRT) for localized prostate cancer
      under field adjustment with gold marker implantation was performed according to
      the treatment strategy based on the clinical risk factors to the patients who
      chose external beam radiotherapy. The treatment strategy contains indications for
      laparoscopic staging lymphadenectomy and neoadjuvant combined androgen blockade
      (CAB). This protocol was applied to 19 patients at Kagawa University Hospital
      from July 2001 to December 2003. The patients were divided into high-risk group
      (n=14): T3-4N0M0 or PSA > or = 20 ng/ml or Gleason sum > or = 8 or suspicious
      node, and low-risk group (n=5): T1c-2bN0M0 and PSA < 20 ng/ml and Gleason sum <
      or = 7 and no suspicious nodes. Basically, high-risk patients underwent
      laparoscopic staging lymphadenectomy prior to radiotherapy. One of the 14
      patients had a positive node and underwent endocrine therapy. The high-risk group
      received neoadjuvant CAB for 3 to 4 months, followed by gold marker implantation.
      One patient chose endocrine therapy at this point. Low-risk patients underwent
      marker implantation without endocrine therapy. Every patient successfully
      completed planned irradiation. The changes of prostate volume and serum PSA after
      neoadjuvant CAB were significant [28.7 ml to 15.7 ml (p=0.004) and 53.9 ng/ml to
      1.4 ng/ml (p=0.023), respectively]. Only one patient in the high-risk group had
      biochemical failure. No grade 3 or 4 adverse events occurred in NCI-CTC grading.
      The analysis of gravity center migration of the implanted gold markers in the
      first 8 patients showed that the planned safety margin might not be wide enough
      to avoid neighboring organ irradiation. These results suggested that 3D-CRT under
      field adjustment with implanted gold markers contributes to both higher efficacy
      and lower morbidity.

PMID- 15518126
TI  - [A case of asymptomatic adrenal hematoma which progressively enlarged during
      follow-up].
AB  - We report a case of asymptomatic adrenal hematoma that enlarged during a 3-year
      follow-up. A 66-year-old woman exhibited a 4 cm right adrenal mass, incidentally
      discovered by computed tomography of abdomen, which progressively enlarged to 6
      cm in diameter during the 3 years. The patient underwent right adrenalectomy with
      a diagnosis of a suspected non-functional adrenal tumor. Histopathological
      examination indicated adrenal hematoma without tumor cells. The patient had
      received aspirin medication for 4 years, and it is possible that the enlargement
      of the mass might have been due to aspirin medication.

PMID- 15518127
TI  - [Long-term survival in patients with metastatic renal cell carcinoma managed with
      conservative therapy: a report of two cases].
AB  - Case 1. A 58-year-old man underwent radical nephrectomy due to a tumor in the
      left kidney (renal cell carcinoma, clear cell subtype, G3, pT1bpN0) in 1988.
      Thirteen years later, he underwent surgical resection of metastases to lung and
      cerebrum and gamma ray knife resection of two other sites of metastases to
      cerebrum in 2001. He had no evidence of disease in April, 2003. Case 2. A 53-year
      old man underwent radical nephrectomy due to a tumor in the right kidney (renal
      cell carcinoma, clear cell type, pT1apN0) in 1987. From 1996 to 2001, irradiation
      therapy to multiple metastases to thoracic vertebrae (50 Gy), rib (50 Gy), para
      aorta lymph nodes (40 Gy), sacrum (44 Gy) and sternum (44 Gy), and surgical
      resection of dermal metastasis were performed. Paraplegia occurred due to
      regrowth of thoracic bone metastasis in December, 2001. In February, 2002, he
      died of septic shock caused by infection of decubitus. Surgical resection and
      palliative therapy of recurrent metastatic foci was useful to improve the quality
      of life and probably prognosis.

PMID- 15518128
TI  - [A case of pyonephrosis caused by a protein calculus in a patient on
      hemodialysis].
AB  - We report a case of pyonephrosis caused by a protein calculus in a patient on
      hemodialysis. A 56-year-old man had been treated with dialysis for five years
      because of end-stage renal failure. The patient complained of right lumbar back
      pain and fever. Computed tomography and an ultrasonography revealed right
      hydronephrosis. Pyonephrosis was strongly suspected. A single-J catheter was
      indwelt, cloudy pus with a terrible smell was discharged. After reducing
      inflammation, a right nephrectomy was performed. The analysis of stone component
      revealed mostly a protein calculus, which was a black and turf-like substance in
      the calices. Patients undergoing dialysis often develop urinary calculi. Some
      calculi are composed of beta2-microglobulin-origin amyloid, which is very
      difficult to find with diagnostic imaging.

PMID- 15518129
TI  - [A case of inflammatory pseudotumor of renal pelvis showing a complete response
      to antibiotics].
AB  - A 20-year-old woman was admitted with chief complaints of high fever and right
      lumbago. Abdominal computed tomography (CT) and ultrasonography revealed a right
      renal pelvic tumor 25 mm in diameter. Although malignancy could not be confirmed
      by the scan, we administered antibiotics based on a diagnosis of inflammatory
      pseudotumor of the renal pelvis. After treatment, no tumor was detected. In such
      cases,because diagnosis is generally difficult, surgery is usually performed.
      However, in this case, the patient showed a complete response to antibiotics.

PMID- 15518130
TI  - [Septic shock following intracavitary Bacillus Calmette-Guerin therapy for
      postcystectomy ureteral cancer].
AB  - A 72-year-old female patient was diagnosed as having a tumor in her bladder at
      the department of obstetrics and gynecology. Transurethral resection of bladder
      tumor was performed in November, 2002. Pathology showed transitional cell
      carcinoma (TCC), G2>G3, pT1. Chemotherapy consisting of methotrexate, adriamycin
      and cisplatin and bladder instillation of Bacillus Calmette-Guerin (BCG) was
      performed. Re-biopsy revealed transitional cell carcinoma, G2, carcinoma in situ
      of the bladder and she received radical cystectomy with ureterocutaneostomy in
      June, 2003. After the cystectomy, the left ureter showed signs of cancer so BCG
      was administered through the left ureterocutaneostomy. During the second
      instillation, she had a high temperature and also exhibited signs of chills with
      frequent shivering followed by dyspnea, severe hypotension and tachycardia. We
      started the patient on dopamine and norepinephrine drips to maintain blood
      pressure and then started isoniazide and meropenem for presumed septic shock. The
      next day, the patient continued to be febrile and her condition deteriorated.
      After she was given endotoxin absorption therapy, she regained normal blood
      pressure and her heart rate, but was still febrile. After 13 days, rifampicin,
      ethambutol, and pyrazinamide were administered and after 18 days predonisolone
      was begun. From that point the patient's general condition gradually improved.

PMID- 15518131
TI  - [A case of transitional cell carcinoma of the renal pelvis with adenocarcinoma
      producing CEA and CA19-9].
AB  - We report a case of invasive renal pelvic tumor with high serum levels of
      carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9). An 86-year-old
      man presented with macrohematuria. Retrograde pyelography demonstrated a filling
      defect in right upper calyx, suspected of renal pelvic tumor. The levels of serum
      CEA and CA 19-9 were elevated to 28.0 ng/ml and 122 U/ml, respectively. No
      abnormalities were found in the gastrointestinal tract. Right nephroureterectomy
      was performed, and histopathological diagnosis was transitional cell carcinoma,
      grade 2>grade 3, accompanied with adenocarcinoma immuno-stained for CEA and CA19
      9. A part of the tumor showed a tubular growth pattern. Both serum levels of CEA
      and CA 19-9 immediately decreased to the normal range after the operation, but
      increased again with lung and hepatic metastases.

PMID- 15518132
TI  - [Endovascular stent graft for management of ureteroarterial fistula: a case
      report].
AB  - We report a case of ureteral-iliac artery fistula and its minimally invasive
      management with endovascular stent grafting. A 76-year-old male was admitted with
      massive gross hematuria from an ilial conduit. He underwent a radical cystectomy
      with ileal loop urinary diversion for bladder cancer 7 months ago and had
      undergone placement of a 7 Fr single-J ureteral catheter for repair of a partial
      disruption of the left ureteroileal anastomosis. Although the fistula was not
      confirmed radiographically, a left ureteral-common iliac artery fistula was
      highly suspected. The patient was treated by percutaneous placement of an
      autoexpandable covered stent graft across the left common iliac and left external
      iliac artery. After successful endovascular management of the ureteroarterial
      fistula, the patient's hematuria resolved and he recovered fully. During 10
      months of follow up, he has been free of hemorrhagic episodes. Because open
      surgical repair may be difficult and associated with significant risk for
      complications, endovascular intervention may provide a safety treatment
      alternative.

PMID- 15518133
TI  - [Signet ring-cell carcinoma of the prostate: a case report].
AB  - A 76-year-old male was admitted with a complaint of dysuria. Serum prostatic
      specific antigen was 28 ng/ml. Transperineal prostatic biopsy was performed and
      histopathological diagnosis was signet ring cell carcinoma with a part of poorly
      differentiated adenocarcinoma. Imaging studies showed that the tumor was
      localized in a large part of the prostate, and no abnormality was found in the
      stomach, the intestine, or the colon. Cystoprostatectomy and ileal conduit
      construction were performed in November 2002. Immunohistochemistry revealed that
      the specimen included the signet ring cells, which were stained for prostate
      specific antigen antibody, but not with periodic acid schiff. He is alive with no
      evidence of disease in 13 months after the operation.

PMID- 15518134
TI  - [Endometrioid adenocarcinoma of the prostate: a case report].
AB  - We report a case of endometrioid adenocarcinoma of the prostate. A 60-year-old
      man visited our hospital with high serum prostate specific antigen (PSA) level
      (6.4 ng/ml). Digital rectal examination revealed prostatic enlargement but no
      induration was palpable. Magnetic resonance imaging (MRI) of the prostate
      demonstrated the low intensity mass lesion around the prostatic urethra on T2
      weighted images. Because a prostate cancer revealed by transrectal and
      transperineal needle biopsy of the prostate, retropubic radical prostatectomy was
      performed and histological finding showed endometrioid adenocarcinoma of the
      prostate. We review 41 cases reported in the Japanese literature and discuss them
      briefly.

PMID- 15518135
TI  - [Alveolar rhabdomyosarcoma originating in spermatic cord: a case report].
AB  - A 19-year-old man visited our hospital complaining of swelling of the left
      inguinal region. A thumb head-sized tumor was palpated through the skin on the
      left spermatic cord. Tumor resection was performed because it was dissected
      easily apart from the left spermatic cord. Pathological examination revealed
      alveolar rhabdomyosarcoma with positive surgical margin. Computed tomographic
      scanning revealed no retroperitoneal lymph node swelling, and there were no
      clinical findings of distant metastasis (clinical stage I). Radical inguinal
      orchiectomy with combined chemotherapy using vincristine, dactinomycin, and
      ifosfamide (VAI) was performed. He has been alive without any recurrence for 8
      years and 8 months after the surgery.

PMID- 15518136
TI  - [Malignant melanoma in penile foreskin].
AB  - We report a case of stage I malignant melanoma of the penis (confined to the
      penis). A 74-year-old uncircumcised man noticed a nonhealing, painless black
      lesion in penile foreskin and visited our institute. As the lesion was confined
      to the prepuce, the patient underwent circumcision for treatment and histological
      diagnosis. Histological examination revealed a malignant melanoma composed of
      epithelioid melanocytes. Ten months later, he is currently alive, without
      recurrence or metastasis.

PMID- 15518137
TI  - [Paraurethral leiomyoma in women].
AB  - We experienced a case of paraurethral leiomyoma in a 36-year-old woman. She had
      been complaining of dysuria. She had noticed the presence of a mass in anterior
      vagina. That mass was about 3 x 3 cm, floating moderately firm with a smooth face
      sited in a paraurethral region. Magnetic resonance imaging showed medium-signal
      intensity on T1-weighted images and a homogeneous low signal on T2-weighted
      images. We diagnosed it as a paraurethral leiomyoma and enucleated it by surgery.
      At histological examination the tumor resulted in being a leiomyoma. The
      diagnosis and the treatment of female paraurethral leiomyoma are discussed.

PMID- 15518138
TI  - [Diagnosis and therapy of diseases of the endocrine system: new trends in nuclear
      medicine].
AB  - Diagnosis and therapy of endocrine disorders in nuclear medicine has been
      improved through the implementation of new techniques especially with positron
      emission tomography (PET). In modern concepts of parathyroid gland surgery an
      exact anatomic localisation of adenomas is necessary, which may be achieved with
      MIBI-Scintigraphy being the most sensitive method in primary hyperparathyroidism.
      The optimal access to localise adenomas is the investigation with combined
      SPECT/X-CT systems. The use of such systems for diagnosing neuroendocrine tumors
      of the gastrointestinal system may also be helpful. For neoplasms of the adrenal
      gland PET systems could be used to differentiate between benign and malignant
      entities or to detect primary tumours. In case of incidentalomas J131
      Norcholesterol and MIGB-scintigraphy has been proven helpful. Indications for
      nuclear medicine studies to detect abnormalities of the hypothalamic-hypophyseal
      system are established rarely.

PMID- 15518139
TI  - [Pathologic-anatomic diagnosis of endocrine neoplasms: new trends and
      applications].
AB  - The pathologic-anatomical diagnosis of endocrine diseases mainly relies on
      established techniques of histology and cytology. Additional immunhistochemical
      tests an the expression analysis may lead to a higher specificity of the
      morphological diagnosis. For thyroid tumours so-called high-throughput methods
      have been established in clinical routine successfully. Calcitonin screening
      tests can be performed routinely in patients with or without an increased risk of
      familiar dominance. For the neuroendocrine neoplasms of the pancreas and the
      gastrointestinal tract a new WHO classification has been established.

PMID- 15518140
TI  - [Minimally invasive endocrine surgery: aspects of diagnostic imaging].
AB  - Since 1997 minimally invasive surgical techniques are used for the treatment of
      diseases of the adrenals, thyroid, parathyroid and the endocrine pancreas. In
      contrast to open surgical procedures special radiological examinations are the
      basis for minimally invasive techniques after biochemical testing. The basis of
      excellent results are a careful evaluation and preparation of the patient in a
      centre with experience in the open techniques and a frequency of at least 20
      endoscopic adrenalectomies a year. Adrenal tumours can be removed endoscopically
      through a transperitoneal or an extraperitoneal route. The endoscopic exploration
      of the parathyroids in patients with biochemically proven primary
      hyperparathyroidism was modified to video-assisted exploration because of the
      long operating times. An alternative to the video-assisted procedure is the
      minimally invasive open exploration. With this technique reoperations can be
      performed and ipsilateral thyroid nodules (found in more than 50% in middle
      Europe) can be removed. Small solitary thyroid nodules are the indication for an
      endoscopic or video-assisted exploration of the thyroid. A laparoscopic
      exploration of the pancreas was performed in 68 patients with neuroendocrine
      pancreatic tumours. The experience of the surgical team improves the
      postoperative long term results, thus minimally invasive endocrine surgery should
      be performed in centres with great experience in the treatment of endocrine
      tumours and with the possibility of close contact to other specialists interested
      in this topic.

PMID- 15518141
TI  - [Diseases of the pituitary gland: clinical aspects and biochemical evaluation].
AB  - Endocrine inactive and prolactin-secreting adenomas are the most commonly
      observed forms of pituitary tumors counting for more than 50 percent of diseases.
      In most cases first clinical symptoms can be attributed to insufficiency of the
      adenohypophysis which is also true for gonadotropin and thyroid stimulating
      hormone (TSH) producing adenomas. Clinical signs and symptoms of secondary
      insufficiency and primary forms of endocrine deficits do not differ significantly
      and the diagnosis may be hampered by involvement of more than one organ system.
      In contrast, symptoms and signs of ACTH or GH producing tumors are more
      impressive leading to diagnosis at an earlier stage. In case of corticotropic and
      somatotropic dysfunction dynamic tests are necessary for diagnosis. Close
      cooperation of endocrinologists, radiologists, and neurosurgeons is necessary for
      the effective workup of pituitary gland diseases.

PMID- 15518142
TI  - [Imaging of tumors of the pituitary gland].
AB  - Macrotumors of the sella region usually involve the suprasellar and less commonly
      the parasellar space. The suprasellar extension of pituitary adenoma, meningeoma,
      craniopharyngioma, and hypothalamic or chiasmatic glioma count for the most
      frequent neoplastic entities. In macroadenomas of the pituitary gland invasion of
      parasellar spaces may occur in 6-10%. Imaging techniques are directed to increase
      the likelihood of surgical cure and to detect aggressive tumour invasion into
      surrounding tissues. A dedicated classification basing on indirect MRI signs of
      tumour extension has been established. With high-resolution high-field (3T) MRI
      the sella region may be displayed to provide better information compared to lower
      field strengths.

PMID- 15518143
TI  - [Pituitary adenomas: neurosurgical treatment].
AB  - Due to their diversity, pituitary adenomas represent an interdisciplinary
      therapeutic challenge in regard to endocrinology, radiology and neurosurgery.
      Advanced radiological methods such as magnetic resonance imaging (MRI) and the
      possibility of three-dimensional reconstruction have profoundly improved surgical
      planning and intraoperative neuronavigation. With the application of modern
      surgical techniques like endoscope-assisted microsurgery or pure endoscopic
      surgery further improvements in the treatment of pituitary adenomas at difficult
      locations can be expected. Major prognostic factors predicting surgical outcome
      are extension of the adenoma and invasivity into adjacent structures. Both may be
      perfectly visualized by high-resolution MRI. The proliferation marker MIB-1 as a
      parameter of growth-rate and invasivity of pituitary adenomas provides
      information for postoperative management in terms of additional treatment and
      follow-up imaging. The current management of pituitary adenomas is discussed
      according to the different therapeutic options available and new developments are
      presented.

PMID- 15518144
TI  - [Diagnostic management of nipple discharge].
AB  - Nipple discharge may be a symptom of a variety of diseases. The importance of
      nipple discharge is its possible association with breast carcinoma. Not only the
      precise clinical evaluation but also particularly imaging evaluation by
      mammography, ultrasound, galactography or MR-galactography is necessary to
      establish the exact diagnosis and plan proper treatment. Depending on the
      underlying pathology--most commonly intraductal papilloma, fibrocystic changes or
      breast carcinoma--the optimal therapeutic regimen, such as single lactiferous
      duct excision on the one end and modified radical mastectomy on the other end of
      the spectra may be chosen.

PMID- 15518145
TI  - [Factors influencing quality of mammograms].
AB  - Due to its outstanding role for screening and diagnosis of breast cancer,
      optimizing the quality of mammographies was in the main focus of interest within
      the past two decades. However, there exist additional, non-technical factors
      influencing diagnostic confidence of mammograms, which were usually not part of
      discussions concerning mammographic image quality. Nevertheless, these non
      technical factors are of great interest into the female population. Information
      and instruction of the patient prior to mammography helps to increase the
      compliance of the patient during mammography, and thus not only cooperation
      during examination is optimized, but also cooperation in the screening program.
      Furthermore, timing the examination within the first part of the menstrual cycle
      and regarding specific patient-related factors can decrease pain and discomfort
      during mammography, which will increase image quality.

PMID- 15518146
TI  - [New insights on the effects of hormone replacement therapy on the breast tissue
      and the orgnaism].
AB  - Within the last fifteen to twenty years extensive discussions were held about
      advantages and disadvantages of postmenopausal hormone replacement therapy.
      Basing on recent data from prospectively randomized studies the long-term
      application of a combined estrogen-gestagen therapy for general prophylaxis
      cannot be recommended. Ongoing studies are expected to provide sufficient data to
      determine regimens for the prevention of osteoporosis, development of cancer, and
      cardiovascular diseases.

PMID- 15518147
TI  - [Imaging of endocrine tumours of the pancreas].
AB  - Islet cell tumors are rare pancreatic or peripancreatic neoplasms that produce
      and secrete hormones to a variable degree. Neuroendocrine tumors of the pancreas
      can occur sporadically or in association with multiple endocrine neoplasia type 1
      (MEN I). Biologically active neuroendocrine tumors produce early symptoms and are
      often difficult to diagnose owing to their small dimensions, whereas biologically
      inactive forms are often large and sometimes found by chance. Imaging has a major
      role in the preoperative localization of the primary tumor and detection of
      metastases, providing an anatomic substrate whereas it plays a primary role in
      the regional staging of these neoplasm, for which surgery is the first and
      essential therapeutic approach. Several techniques are available including
      computed tomography (CT), magnetic resonance imaging (MRI), endoscopic
      ultrasound, intraoperative ultrasound, somatostatin receptor scintigraphy, and
      arterial stimulation with venous sampling; each with unique advantages and
      certain limitations. Recent technical advances in Multidetector CT, and dynamic
      MRI using breath hold sequences have improved the sensitivity of these modalities
      markedly.

PMID- 15518148
TI  - [Interventional therapy of neuroendokrine tumors of the gastrointestinal tract].
AB  - Neuroendocrine tumors are rare and slowly progressing malignancies, developing
      predominantly in the gastrointestinal tract. Thus, symptoms often develop late in
      patients with advanced disease. In 40-60% of patients, liver metastases are
      already unresectable and the resultant liver insufficiency is a common cause of
      death. A more aggressive role by the radiologist in diagnosis and interventional
      management of liver metastases using transarterial (chemo)embolisation and
      percutaneous ablation techniques such as using ethanol, laser, and radiofrequency
      did not seriously interfere with the lifestyle of the patient and improved
      survival. Due to many variables of the interventional techniques used and due to
      the low incidence of neuroendocrine tumors, no randomized data is available.
      However, the low morbidity of interventional management in neuroendocrine liver
      metastasis allows effective therapy with good palliation.

PMID- 15518149
TI  - [Imaging of tumours of the adrenal gland].
AB  - For differentiation of benign and malignant adrenal lesions, sensitivities and
      specificities of 85-100% can be reached by unenhanced computed tomography (CT)
      methods, chemical shift techniques in magnetic resonance imaging (MRI), delayed
      enhanced CT-techniques, and by evaluation of wash-out curves in contrast enhanced
      CT or MRI. An increasing number of adrenal lesions that are detected on imaging
      studies for indications unrelated to the adrenals can be immediately
      characterized by delayed series nowadays. According to excellent results of CT
      and MRI in characterization of adrenal masses, the indications for fine needle
      aspiration biopsy have already regressed as well as complications associated with
      this invasive technique.

PMID- 15518150
TI  - [Imaging of diseases of the thyroid gland in Austria].
AB  - Imaging techniques for first line investigation of diseases of the thyroid gland
      are sonography (US) and scintigraphy, followed in dedicated cases by magnetic
      resonance imaging (MRI). Malignant lesions are generally hypoechoic on US with
      calcifications visible in some cases. The appearance of lymph node metastases is
      similar to that of the primary tumour. The various forms of goiter are the most
      commonly occurring forms of thyroid diseases in Austria, they appear heterogenous
      with hyperechoic as well as hypoechoic or anechoic nodes, in some cases with
      calcification. US findings of thyreoiditis are in acute forms of the disease more
      hypoechoic with diffuse swelling and hyperechoic with scar formations in chronic
      forms. Ectopic thyroid tissue occurs often in the form of thyroglossal duct cysts
      which are anechoic or hypoechoic.

PMID- 15518151
TI  - [Imaging of the parathyroid gland].
AB  - Diseases of the parathyroid gland are rare and are especially in case of
      hyperparathyroidism associated with hyperacalcaemia. Enlarged glands are,
      therefore, generally not detected with imaging modalities. The aim of imaging
      studies is to locialize abnormal glands. Ultrasound is the modality of choice for
      the primary investigation followed by nuclear medicine studies. Computed
      tomography or angiography with vein sampling should only be performed if the
      results of other investigations are equivocal. Magnetic resonance imaging is
      performed rarely in Austria with its high prevalence of endemic goiter.

PMID- 15518152
TI  - [Demineralising osteopathies: new aspects of diagnostic imaging].
AB  - The wide use of multimodal radiologic analysis of bone tissue has led to a new
      concept of the term osteopenia towards grouping the various osteopathies as
      demineralizing osteopathies. With bone densitometry measurements both high
      precision and accuracy can be achieved, whereas conventional radiographs provide
      insights into the architecture of the bone to better advantage. By using both
      modalities discrepancies of the radiological reports with the final diagnosis may
      be avoided. Despite ongoing success in techniques of semi-automated data analysis
      and reporting the radiological and the clinical assessment of bone diseases are
      still an indispensable part of establishing the diagnosis.

PMID- 15518153
TI  - [Hybrid imaging for endocrine diseases: new perspectives].
AB  - Hybrid Imaging, also termed dual modality imaging, is the technique of
      fusionizing and interpreting images, that are gained from two different
      modalities constructed in one unit. Therefore, hybrid imaging may be regarded as
      a form of image fusion. Clinical applications in the field of endocrinology are
      the localization of neuroendocrine tumors and of lesions of the adrenal or the
      parathyroid glands. Significant diagnostic impact can be gained with this
      technique influencing the certainty of radiological reports.

PMID- 15518154
TI  - Recognising the wider needs of families.

PMID- 15518155
TI  - Bedsharing and co-sleeping.

PMID- 15518156
TI  - Working together to make a difference.

PMID- 15518157
TI  - Motions required: have your say.

PMID- 15518158
TI  - The future of midwifery: steering a course.

PMID- 15518159
TI  - RCM gears up for polling day.

PMID- 15518160
TI  - More flexible education programmes: increasing options within the NHS.

PMID- 15518161
TI  - Normal birth--is it possible in the 21st century?

PMID- 15518162
TI  - Changes and challenges.
AB  - Although I have discussed the challenges associated with establishing this role,
      on reflection I think this is possibly one of the best jobs in midwifery today.
      The diversity experienced through the post is amazing and the ability to work
      clinically, while having a leadership role that impacts on the service, research
      and education agendas, is both powerful and unique. I hope this has given you
      some insight into my post and demonstrated how innovative and exciting the
      consultant role actually is. I believe these posts have real potential to
      influence our profession and the service we provide for women and families and
      hope this is evident. However, none of this can be achieved without networking
      and having the support of a range of people across a variety of organisations.

PMID- 15518163
TI  - Where do I fit in?

PMID- 15518164
TI  - Women who choose CS.

PMID- 15518165
TI  - Formula milk advertising.

PMID- 15518166
TI  - MSWs in Holland.

PMID- 15518167
TI  - Inhibitory effects of Scutellaria barbata D. Don. and Euonymus alatus Sieb. on
      aromatase activity of human leiomyomal cells.
AB  - It is now well documented that a large proportion of breast tumors express their
      own aromatase. This intratumoral aromatase produces estrogen in situ and
      therefore may contribute significantly to the amount of estrogen to which the
      cell is exposed. Thus it is not only important that aromatase inhibitors potently
      inhibit the peripheral production of estrogen and eliminate the external supply
      of estrogen to the tumor cell, but that they in addition potently inhibit
      intratumoral aromatase and prevent the tumor cell from making its own estrogen
      within the cell. To study the inhibition of intracellular aromatase, we have
      examined the aromatase-inhibiting potency of the Scutellaria barbata D. Don. (SB)
      and Euonymus alatus Sieb. (EA) in myometrial and leiomyomal cells which contain
      aromatase. We have also used human placental tissues. Although SB and EA are
      approximately equipotent in a cell-free aromatase system (human placental
      microsomes), EA is consistently 10-30 times more potent than SB in inhibiting
      intracellular aromatase in myometrial and leiomyomal cells. To provide insights
      into the effect of SB and EA on aromatase activity in leiomyomal cells, we
      examined the cell lines, which is induced to differentiate toward the more
      transformed cell phenotype by 12-tetradecanoylphorbal-13-acetate (TPA) as a
      protein kinase C activator and transforming growth factor-beta1 (TGF-beta1).
      Enzyme activity was inhibited in a time-and dose-dependent fashion by SB and EA
      and by either 1-50 nM TPA or 0.01-0.5 ng/ml TGF-beta1, with maximal responses
      after 2-3 h exposure.

PMID- 15518169
TI  - In vitro cytotoxicity of Mokko lactone in human leukemia HL-60 cells: induction
      of apoptotic cell death by mitochondrial membrane potential collapse.
AB  - We studied the effect of mokko lactone (ML) isolated from the roots of Saussurea
      lappa (Compositae), a plant that is used for medicinal purposes in Korea, on the
      induction of apoptosis in human leukemia HL-60 cells. ML was cytotoxic to HL-60
      cells, and this cytotoxic effect of ML appears to be attributable to its
      induction of apoptotic cell death, as ML induced nuclear morphologic changes and
      internucleosomal DNA fragmentation and increased the proportion of Annexin V
      positive cells and the activity of caspase-3. Further studies revealed that the
      induction of apoptosis by ML was associated with the loss of mitochondrial
      membrane potential. Collectively, our results suggest that apoptosis induced by
      ML in HL-60 cells was executed by a collapse of mitochondrial membrane potential
      followed by the activation of caspase-3. This is the first report on the
      mechanism of apoptosis-inducing effect of ML.

PMID- 15518168
TI  - Differential inhibition of Scutellaria barbata D. Don (Lamiaceae) on HCG-promoted
      proliferation of cultured uterine leiomyomal and myometrial smooth muscle cells.
AB  - Scutellaria barbata D. Don (Lamiaceae)(SB) is a perennial herb which is natively
      distributed throughout Korea and southern China. This herb is known in
      traditional Chinese Medicine as Ban-Zhi-Lian and traditional Korean medicine as
      Banjiryun, respectively. SB has been used as an anti-inflammatory and antitumor
      agent. We aimed to determine the expressin of cell cycle-related signal molecules
      for growth inhibition after HCG treatment by the herb SB in two different human
      myometrial smooth muscle cells (SMCs) and leiomyomal SMCs. Water-soluble
      ingredients of SB, myometrial SMCs and the leiomyomal cell lines were used in
      vitro. Uterine myomas often enlarge rapidly during pregnancy, implying that human
      chorionic gonadotrophin (HCG) may influences cell proliferation in uterine
      leiomyomata. We investigated the effects of SB on the cell proliferation and the
      expression of cell cycle-related proteins in these cells. Although HCG/LH
      receptor was present in both cultured myometrial and leiomyomal cells, as assayed
      by reverse transcription polymerase chain reaction analysis, treatment with HCG
      significantly increased cell proliferation in both myometrial and leiomyomal
      cells. However, SB reduced the proliferative effect of HCG in leiomyoma and
      myometrial cells, respectively. In HCG-treated leiomyomal cells, the expression
      of proliferating cell nuclear antigen, cyclin E and cdc2 was significantly
      reduced by SB treatment. These results suggest that SB reduced the HCG-promoted
      proliferation of myometrial and leiomyomal cells.

PMID- 15518170
TI  - Induction of a TC1-mediated experimental autoimmune thyroiditis by deglycosylated
      porcine thyroglobulin.
AB  - Contribution of cytotoxic T lymphocytes (CTL) to experimental autoimmune
      thyroiditis (EAT) was well defined (Speidel et al., Eur. J. Immunol. 1997, 27,
      2391-2399, Ref. 7). The native porcine thyroglobulin (pTg) showed high
      sensitivity to endo-o-N-acetylglucosaminidase F (Endo F) and its molecular
      weights, corresponding to about 330 kDa as a monomer and 660 kDa as a dimer, were
      reduced to smaller molecular weight forms by Endo F and trifluoromethanesulfonic
      acid (TMSF). Deglycosylated porcine Tg (dgpTg) and native pTg were injected i.v.
      into CBA/J mice, without the aid of adjuvants. Both lymphocytic infiltrations of
      the thyroid glands and levels of Tg-specific CTL were similar to those found in
      conventional EAT induced by Tg and adjuvants. In contrast, proliferative
      responses in native pTg and dgpTg-injected mice could not be detected, and titers
      of antibodies to pTg and dgpTg were 20 times and 30 times lower than that of pTg
      and adjuvants, respectively. The EAT-inducer CTL belonged to the CD8+ cell subset
      and exerted their thyroiditogenic potential through release of IFN-gamma. It was
      concluded that dgpTg-induced EAT is mediated by type 1 cytotoxic T cells (Tcl).
      Also, results that EAT induction of the glycosylated pTg (gpTg) was much lower
      than that of dgpTg, suggested that the abberant and incomplete glycosylation of
      the thyroglobulin is responsible for the induction of autoimmune thyroiditis.

PMID- 15518171
TI  - Inhibitory activity of Drynariae rhizoma extracts on cathepsin having bone
      resorption activity.
AB  - Effects of traditional Korean (Hanbang) medicine, Drynariae rhizoma (DR), on the
      protease activity of bone loss-initiation in rats and mice were investigated.
      Ethanol extracts-DR (EE-DR) and water extracts-DR (WE-DR) were identified as
      potent inhibitor of cathepsins K and L. The original WE-DR inhibits cathepsins K
      and L with IC50 values of 3.7 microg/ml and 4.5 microg/ml, respectively. EE-DR
      was more potent than that of WE-DR, because the inhibitions of cathepsin K and L
      increased to 0.5 microg/ml and 0.8 microg/ml, respectively. The EE-DR was proved
      to be the most potent. EE-DR was found to be a potent inhibitor of cathepsins K
      with a Ki value of 5.0 microg/ml for cathepsin K. The activity was increased by
      10-fold when the assay is performed in the presence of glutathione at pH 7.0,
      which favors the formation of a GSH thiolate anion. Thus, it is suggested that
      this increase in potency is probably due to an enhanced chemical reactivity of
      the extract mixtures toward the thiolate of the active site of the enzyme. WE-DR
      exhibited time-dependet inhibition which allowed us to determine the association
      and dissociation rate constants with cathepsin K. Finally, EE-DR inhibits bone
      resorption in an in vitro assay involving mouse osteoclasts and bovine bone with
      an IC50 value of 70 microg/ml. WE-DR represents a new herbal formulation
      inhibiting cathepsin K and L activity and proteolysis of bone collagen. These
      results strongly suggest that DR is effective for preventing the development of
      bone loss induced by cathepsin K. This result also suggested that the DR is
      effective for bone resorptive action in bone cells.

PMID- 15518172
TI  - Nigerooligosaccharides augments mitogen-induced proliferation and suppresses
      activation-induced apoptosis of human peripheral blood mononuclear cells.
AB  - Nigerooligosaccharides (NOS), a mixture of nigerose and
      nigerosylmaltooligosaccharides, consists of immunopotentiating oligosaccharides
      found in foodstuffs. We have previously reported that activation of peripheral
      blood mononuclear cells (PBMC) in response to concanavalin A (Con A) or a
      streptococcal preparation of OK-432 is augmented in healthy young adults and
      elderly subjects after the intake of NOS-supplemented syrup. A reappraisal of the
      data suggests that NOS augments proliferation but partly suppresses activation
      induced apoptosis of PBMC in response to these mitogens. To confirm this
      hypothesis, PBMC from healthy male subjects were stimulated with Con A or OK-432
      in the presence of nigerose at the concentrations at which it was detected in the
      blood of subjects who had ingested NOS-supplemented syrup. Cellular activation,
      specifically metabolic demand, viability and proliferation, was assessed from
      glucose consumption, by WST-1 colorimetry and by 5-bromo-2'-deoxy-uridine
      incorporation assay, respectively. The Con A-induced activation of PBMC in each
      measurement was significantly augmented by nigerose. OK-432-induced decreases in
      the viability of PBMC were significantly inhibited by nigerose. Stimulation of
      PBMC with Con A or OK-432 induced apoptosis, but nigerose suppressed such
      activation-induced cell death. These results indicated that nigerose activated
      PBMC in vitro in a manner similar to the process observed in vivo, providing
      further evidence for the effectiveness of consumption of NOS-supplemented syrup.

PMID- 15518173
TI  - Inhibitory effect of water-soluble chitosan on TNF-alpha and IL-8 secretion from
      HMC-1 cells.
AB  - Mast cells are known to play an active role as effector cells in allergic
      inflammation and in diverse immunological and pathological processes. Activated
      mast cell-derived pro-inflammatory cytokines are important pathologic factors of
      progression of allergic inflammation. In this study, we investigated whether pro
      inflammatory cytokines (TNF-alpha and IL-8) can be induced by calcium stimulation
      in HMC-1 cells, and high molecular weight water-soluble chitosan (WSC) can
      inhibit the production of these cytokines. We provided evidence that the
      secretion of TNF-alpha and IL-8 from HMC-1 cells was induced by Ca2+-ionophore
      A23187 or Ca2+-ATPase inhibitor TSG. Treatment of WSC (10 microg/ml) prior to
      stimulation with calcium agonists significantly blocked the secretion of TNF
      alpha by 65.1% for A23187 and 87.7% for TSG. IL-8 secretion in response to A23187
      or TSG was inhibited by 49.2% for A23187 and 34.1% for TSG, respectively,
      compared to absence of WSC. These results suggest that WSC has potential
      regulatory effects on allergic inflammatory diseases by down-modulating Ca2+
      induced mast cell activation.

PMID- 15518174
TI  - Immunostimulatory role of tryptic digest of Abrus agglutinin.
AB  - Many bioactive peptides are in therapeutic use as immunomodulators at present.
      The origin of these bioactive peptides is diverse. Such bioactive peptides are
      reported to be present in enzymatic digest of food and milk proteins. In our
      previous work we have reported that Abrus agglutinin retains its bioactivity even
      after heat denaturation but loses its haemagglutination properties. This leads to
      the supposition that immunostimulatory regions in the protein might be
      responsible for its in vivo and in vitro stimulatory properties. Thus the
      bioactivity of tryptic digest of Abrus agglutinin (TDA) was checked in vitro to
      ascertain the presence of some bioactive region in the protein, which will lead
      to the discovery of certain immunostimulatory peptides which might be of use in
      nonspecific immunotherapy. In this study it is observed that TDA stimulates
      macrophage increasing the phagocytic and bactericidal activity as well as
      hydrogen peroxide production. TDA also proliferates splenocytes leading to Th1
      response and NK cell activation.

PMID- 15518175
TI  - Adjunct effect of immunostimulating hexapeptide analogous to human beta-casein
      fragment (54-59) to sodium stibogluconate against experimental visceral
      leishmaniasis.
AB  - Visceral leishmaniasis (VL) is a major public health problem in many tropical
      countries of the world. The available chemotherapeutics require parenteral
      administration and have other limitations like cost, toxicity, variable efficacy
      or restricted supplies. There is no effective treatment for immunosuppressed
      patients with leishmaniasis- HIV co-infection. Hence, new therapies, that are
      effective when treatment with the currently available drugs fails, must be
      developed. One of the major strategies for effective and safe treatment of
      leishmaniasis and other infectious diseases, in the last decade, involves the use
      of immunomodulators as adjunct to chemotherapy. In this context, we studied the
      immunomodulatory activity of a hexapeptide Val-Glu-Pro-Ile-Gly-Tyr (CDRI compound
      89-215) corresponding to (54-59) fragment of human beta-casein in mice and its
      efficacy in adjunct chemotherapy with SSG using L. donovani/hamster model. The
      hexapeptide was found to enhance both humoral and CMI responses. In animal model
      the hexapeptide per se showed no antileishmanial activity. However, when given
      alongwith suiboptimal dose of SSG, it enhanced the efficacy of SSG from 24% to
      80%. The activity was very close to the efficacy (85%) recorded for curative dose
      of SSG. Adjunct chemotherapy with immunomodulator in visceral leishmaniasis
      appears to be a fruitful preposition.

PMID- 15518176
TI  - The in vivo effects of cytokines modulation for BALB/C mice fed with a
      traditional combined chinese herb-soaked solution, Yi-Fey Ruenn-Hou tea.
AB  - An experiment was conducted to investigate the effects of Yi-Fey Ruenn-Hou (YR)
      Tea, a combination of Chinese herbs, 10% licorice root, 10% American ginseng, 10%
      Radix Paeoniae alba and 70% green tea-soaked solution, on the cytokine modulation
      in Balb/C mice. Four groups of mice were administered either 1ml of drinking
      water (group A) or 2 mg/ml (group B), 8 mg/ml (group C), 40 mg/ml (group D) of a
      saturated solution of combined Chinese herbs daily for six months. The
      physiological and pathological characteristics of the mice were observed during
      the time, and the mice were weighed and at least two mice were sacrificed each
      month for pathological detection of the brain, heart, liver, spleen and kidney
      and cytokine analysis. The results revealed neither weight difference nor
      pathological change among the four groups, however, serum-cytokine assay
      indicated that the cytokine modulation effects are consistent, and the most
      obvious cytokine modulation effect was observed in group D, which was the highest
      dosage employed for treating the mice. TH2-pattern cytokines responded earlier
      and higher in group D than in groups B and C. Furthermore, the effect of YR Tea
      on cytokine modulation in vivo is predominantly TH2-pattern and is dependent on
      its dosage (P < 0.05).

PMID- 15518177
TI  - Effect of Boo Yong-Tang on mast cell-mediated allergic reaction.
AB  - Boo Yong-Tang (BYT) is an Oriental herbal prescription, which has been clinically
      applied for treatment of allergic disorders. Here, we report inhibitory effects
      of BYT on experimental allergic reactions. BYT increased interferon-gamma
      secretion from MOLT-4 T cells. When BYT (0.01, 0.1, or 1 g/kg) was orally
      administered for 1 h in mice, compound 48/80-induced ear swelling was
      significantly reduced. BYT also inhibited the histamine release from the mast
      cells activated by compound 48/80. In addition, BYT showed an inhibitory effect
      of anti-dinitrophenyl IgE antibody-induced passive cutaneous anaphylaxis
      reaction. These findings provide evidence that BYT is a potential prescription
      for the treatment of allergic reaction through down-modulating of mast cell
      activation.

PMID- 15518178
TI  - Myelopoietic response in mice exposed to acute cold/restraint stress: modulation
      by Chlorella vulgaris prophylactic treatment.
AB  - In this study, hematopoietic cells from mice pretreated with CVE and exposed to
      acute cold/restraint stress were stimulated in the presence of growth factors to
      form colonies, thus providing accurate information about the modulation of the
      green algae of the stress-induced changes in the hematopoietic response. Our
      results demonstrated that exposure to acute stress affected hematopoiesis. Mice
      exposed for a 2.5-hour time period of cold and restraint presented diminished
      clonal capacity for CFU-GM content per femur, which was decreased by as much as
      50% compared with that in control mice, in spite of the significant increase in
      serum colony-stimulating activity (CSA). Treatment with 50 mg/kg CVE for 5 days,
      previously to the stress regimen, attenuates the effects of the stress, since
      comparable levels of myeloid progenitors were found in the bone marrow of both
      CVE/stress and control mice. Moreover, the sera from stressed mice pretreated
      with CVE further increased the CFU-GM formation. On the contrary, the spleen
      seemed to be less sensitive to acute stress in our experimental conditions. These
      findings are in line with our previous reports showing that the stress-induced
      reduction in bone marrow CFU-GM of rats exposed to electric shocks is mediated by
      activation of the HPA axis and by secretion of opioid agonists. No changes were
      observed in bone marrow, spleen and thymus total cell counts, and in relative
      organ weights. However, a 50% reduction in the body weight loss produced by the
      stress was observed in mice given the extract.

PMID- 15518179
TI  - Immune tolerance to drugs. (II).: Long-term tolerability of nimesulide in
      patients with NSAID hypersensitivity.
AB  - Nimesulide is well-tolerated as an alternative to nonsteroidal antiinflammatory
      drugs (NSAIDs) in patients with a previous adverse reaction to other classes of
      NSAIDs. However, there is little information in the literature about its long
      term tolerability. The study was carried out on 625 patients who had experienced
      adverse reactions to one or more NSAIDs. All patients received and tolerated
      peroral challenges with nimesulide. On the first day, patients were given an
      equivalent number of placebo doses to the planned number of nimesulide doses. In
      a successive session, the test was administered by means of increasing doses of
      nimesulide at 30 min intervals until the common daily therapeutic dose of 100 mg
      was reached (10 mg-20 mg-30 mg-40 mg). A questionnaire was distributed to all
      subjects. In particular, they were asked to clarify any reactive symptoms they
      had developed after ingestion of the drug. It was found that only 2.1% (4/192) of
      subjects who were given this drug experienced urticaria during treatment. We have
      identified three significant risk factors: a history of chronic urticaria, a
      history of antibiotic hypersensitivity and a history of hypersensitivity to more
      than one class of NSAIDs. In patients with the above risk factors, a prior
      tolerance test with a selective COX2 antagonist should be administered.

PMID- 15518180
TI  - Allergic contact dermatitis to condoms: description of a clinical case and
      analytical review of current literature.
AB  - We describe the case of a 42-years-old non-atopic man who developed a severe
      eczematous reaction in the genital area some hours after the use of a condom
      (Settebello-Hatu Durex) containing a retarding cream. Patch test revealed a
      strong allergic reaction to the retarding cream and to benzocaine and paraben mix
      contained in the cream itself. Condoms with retarding cream should be avoided in
      man sensitized to local anestethetics.

PMID- 15518181
TI  - [The systems of neurochemical regulation at brain pathologies].
AB  - The paper summarises the comprehensive concept on main groups of chemical
      substances and on their diverse regulatory function in the brain.
      Neurotransmitters, neuropeptides, neurotrophic and growth factors, and cytokines
      are considered as many-storied, integral structure. The proper analysis of
      ischemic and neurodegenerative brain disturbances evidently demonstrates the
      active participation of basic families of these chemical regulators at all stages
      of the pathogenesis. The main theoretical positions involving these regulatory
      substances in the control of normal and pathological situations include: (a)
      dogma on the imbalance of chemical regulators, as the initial pathogenetic
      principle; (b) genetically heterogeneity of brain structures, which demonstrate
      selective vulnerability or, to the contrary, steadiness for damaging exposure. As
      a general principle for increasing number of clinical and experimental
      pathologies, the induction of apoptic cascade processes is postulated; their
      "normal" biological function in nervous tissues is a key factor for development
      of majority of brain diseases.

PMID- 15518182
TI  - [General hormonology].
AB  - Research of hormones and mechanisms of their action is one of the most rapidly
      developing branches of modern biology. During the last 15 years it has been shown
      that hormones regulate all vital processes: metabolism and functions as well as
      template syntheses and other cellular processes (proliferation etc.), determined
      by genome. The majority of hormones showed new effects, their action proved to be
      pleiotropic. The comparative analysis has shown the fundamental uniformity of
      biological functions and signification, the basic features and properties,
      molecular mechanisms of action for all types of intercellular receptor
      regulators' activity. Therefore they are appropriate to be combined into a
      complete community, so-called "hormones". The science of all hormones is to be
      defined as hormonology. The activity of hormones considerably changes upon many
      diseases. Substances, which influence hormonal systems, make 2/3 of modern
      medications.

PMID- 15518183
TI  - [Study of the mouse liver microsomes by the methods of proteome analysis].
AB  - Proteome maps of microsomes and their ghosts (i.e. membranes purified from
      "ballast" proteins) were obtained using highly purified mouse liver microsomes.
      Comparative analysis of protein composition of ghosts without and after the
      induction with phenobarbital (cytochromes P450 inducer) by using 1D- and 2D
      electrophoresis and MALDI-TOF-mass-spectrometry revealed more than 30 new
      proteins, in the course of induction in the 45-60 kDa range (corresponding to the
      mol. weights of cytochromes P450). In the 17 kDa range (corresponding to the mol.
      wt. of cytochrome b5) there were 4 additional protein stains about 20 proteins
      disappeared over the entire electrophoregram). Separation of microsomal ghosts
      proteins by 1D electrophoresis followed by mass-spectrometric analysis allowed to
      identify cytochromes P450. The present investigation demonstrates the efficiency
      of different proteomic methods combination (1D- and 2D-electrophoresis, mass
      spectrometry, bioinformatics and determination of the enzyme activities) for
      cytochromes P450 identification and elucidation of their functioning in different
      animal tissues and then extrapolating this approach to humans.

PMID- 15518184
TI  - [Biological properties of L-lysine alpha-oxidase in native and conjugated form].
AB  - The significant difference between biological properties of L-lysine-alpha
      oxidase from Trichoderma harzianum Rifai (LO) and L-asparaginase from E. coli has
      been observed in vitro and in vivo. High antitumor activity was shown against 8
      types of murine and rat transplanted tumors with a wide range of LO therapeutic
      doses: 35-350 U/mg. The LO conjugates with monoclonal antibodies CD5 specific to
      the surface of cell line Yurkat were obtained without significant loss of either
      enzymatic and cytotoxic activity or immunological specificity. The further
      perspective investigation for the clinical application of the native or
      conjugated enzymes is discussed.

PMID- 15518185
TI  - [Biochemical basis of valproic acid toxicity: role of oxidative stress and
      effects of L-carnitine].
AB  - Reduced hepatic mitochondrial beta-oxidation and changes in L-carnitine
      metabolism are important biochemical manifestations of valproate (VA)-induced
      hepatic toxicity. Lipid peroxidation activation as a possible mechanism
      implicated in VA-induced damage as well as the possibility of L-carnitine (LC)
      attenuation of lipid peroxidation activity were studied. The level of
      malondialdehyde (MDA), lipid peroxide concentration and antioxidant activity
      (AOA), catalase activity, free S-S groups content in plasma and liver homogenates
      from male albino rats supplemented with VA (200 mg/kg, 8 days) and VA plus LC
      (100 mg/kg, 8 days) were measured. There were insignificant differences in MDA
      formation and catalase activity in the plasma and liver of control and VA-treated
      groups, however decreases in the plasma AOA activity and S-S groups level were
      observed in VA-treated rats. The LC administration significantly decreased liver
      lipid peroxide concentration and increased plasma AOA activity and S-S groups.
      Our results suggest that lipid peroxidation may be involved as an additional
      mechanism for VA-induced liver damage in rats. The potential antioxidant activity
      of LC may be particularly relevant in understanding the pharmacological and
      biochemical properties of LC in VA-induced pathologic conditions.

PMID- 15518186
TI  - [Using thioGlo-1 for the determination of thiols in brain tissue].
AB  - A technique for the fluorometric determination of protein and non-protein thiols
      in brain tissue with the maleimide reagent ThioGlo-1is has been described.
      Comparison with the most popular spectrophotometric Ellman method has been
      performed. The ThioGlo-1-based method is highly sensitive and may be used for
      thiol determination both in homogenates and supernatants of brain tissue.

PMID- 15518187
TI  - [Metabolic state of erythrocytes under gall-stone disease].
AB  - Metabolic state of erythrocytes is changed under gall-stone disease. The increase
      of glucose and glycated hemoglobin contents in erythrocytes is combined with
      intensification of glycolytic reactions and lowered activity of pentose phosphate
      pathway. These changes may have compensative importance.

PMID- 15518188
TI  - Molecular genetics of color-vision deficiencies.
AB  - The normal X-chromosome-linked color-vision gene array is composed of a single
      long-wave-sensitive (L-) pigment gene followed by one or more middle-wave
      sensitive (M-) pigment genes. The expression of these genes to form L- or M-cones
      is controlled by the proximal promoter and by the locus control region. The high
      degree of homology between the L- and M-pigment genes predisposed them to unequal
      recombination, leading to gene deletion or the formation of L/M hybrid genes that
      explain the majority of the common red-green color-vision deficiencies. Hybrid
      genes encode a variety of L-like or M-like pigments. Analysis of the gene order
      in arrays of normal and deutan subjects indicates that only the two most proximal
      genes of the array contribute to the color-vision phenotype. This is supported by
      the observation that only the first two genes of the array are expressed in the
      human retina. The severity of the color-vision defect is roughly related to the
      difference in absorption maxima (lambda(max)) between the photopigments encoded
      by the first two genes of the array. A single amino acid polymorphism (Ser180Ala)
      in the L pigment accounts for the subtle difference in normal color vision and
      influences the severity of red-green color-vision deficiency. Blue-cone
      monochromacy is a rare disorder that involves absence of L- and M-cone function.
      It is caused either by deletion of a critical region that regulates expression of
      the L/M gene array, or by mutations that inactivate the L- and M-pigment genes.
      Total color blindness is another rare disease that involves complete absence of
      all cone function. A number of mutants in the genes encoding the cone-specific
      alpha- and beta-subunits of the cGMP-gated cation channel as well as in the alpha
      subunit of transducin have been implicated in this disorder.

PMID- 15518189
TI  - Characterization of a novel form of X-linked incomplete achromatopsia.
AB  - X-linked incomplete achromatopsia (XIA), also called blue-cone monochromacy
      (BCM), is a rare cone disorder that most commonly results either from one of two
      conditions. The first condition is a deletion of the locus control region (LCR)
      which is a critical DNA element that lies upstream of the L and M photopigment
      gene array on the X-chromosome and is necessary for expression of the
      photopigment genes. The second condition is an inactivating point mutation within
      the coding sequence of the remaining photopigment gene in an array from which all
      but one gene has been deleted. Many previous studies have concluded that affected
      individuals either have only rods and S-cones (Blackwell & Blackwell, 1957, 1961;
      Daw & Enoch, 1973; Hess et al., 1989) or have rods, S-cones, and another cone
      type that contains the rod pigment (Pokorny et al., 1970; Alpern et al., 1971).
      However, Smith et al. (1983) described individuals with XIA who had residual L
      cone function. Here we report results for a subject with XIA who appears to have
      residual M-cone function. Genetic analysis revealed that he had apparently normal
      genes for M-cone photopigment thus leaving open the possibility that he has a
      contribution to vision based on expression of these genes at a very low level.

PMID- 15518190
TI  - Variety of genotypes in males diagnosed as dichromatic on a conventional clinical
      anomaloscope.
AB  - The hypothesis that dichromatic behavior on a clinical anomaloscope can be
      explained by the complement and arrangement of the long- (L) and middle
      wavelength (M) pigment genes was tested. It was predicted that dichromacy is
      associated with an X-chromosome pigment gene array capable of producing only a
      single functional pigment type. The simplest case of this is when deletion has
      left only a single X-chromosome pigment gene. The production of a single L or M
      pigment type can also result from rearrangements in which multiple genes remain.
      Often, only the two genes at the 5' end of the array are expressed; thus,
      dichromacy is also predicted to occur if one of these is defective or encodes a
      defective pigment, or if both of them encode pigments with identical spectral
      sensitivities. Subjects were 128 males who accepted the full range of admixtures
      of the two primary lights as matching the comparison light on a Neitz or Nagel
      anomaloscope. Strikingly, examination of the L and M pigment genes revealed a
      potential cause for a color-vision defect in all 128 dichromats. This indicates
      that the major component of color-vision deficiency could be attributed to
      alterations of the pigment genes or their regulatory regions in all cases, and
      the variety of gene arrangements associated with dichromacy is cataloged here.
      However, a fraction of the dichromats (17 out of 128; 13%) had genes predicted to
      encode pigments that would result in two populations of cones with different
      spectral sensitivities. Nine of the 17 were predicted to have two pigments with
      slightly different spectral peaks (usually < or = 2.5 nm) and eight had genes
      which specified pigments identical in peak absorption, but different in amino
      acid positions previously associated with optical density differences. In other
      subjects, reported previously, the same small spectral differences were
      associated with anomalous trichromacy rather than dichromacy. It appears that
      when the spectral difference specified by the genes is very small, the amount of
      residual red-green color vision measured varies; some individuals test as
      dichromats, others test as anomalous trichromats. The discrepancy is probably
      partly attributable to testing method differences and partly to a difference in
      performance not perception, but it seems there must also be cases in which other
      factors, for example, cone ratio, contribute to a person's ability to extract a
      color signal from a small spectral difference.

PMID- 15518191
TI  - Cone pigment polymorphism in New World monkeys: are all pigments created equal?
AB  - Most platyrrhine monkeys have a triallelic M/L opsin gene polymorphism that
      underlies significant individual variations in color vision. A survey of the
      frequencies of these polymorphic genes suggests that the three alleles occur with
      equal frequency among squirrel monkeys (subfamily Cebinae), but are not equally
      frequent in a number of species from the subfamily Callitrichinae. This departure
      from equal frequency in the Callitrichids should slightly increase the ratio of
      dichromats to trichromats in the population and significantly alter the relative
      representation of the three possible dichromatic and trichromatic phenotypes. A
      particular feature of the inequality is that it leads to a relative increase in
      the number of trichromats whose M/L pigments have the largest possible spectral
      separation. To assess whether these trichromatic phenotypes are equally well
      equipped to make relevant visual discriminations, psychophysical experiments were
      run on human observers. A technique involving the functional substitution of
      photopigments was used to simulate the discrimination between fruits among a
      background of leaves. The goal of the simulation was to reproduce in the cones of
      human observers excitations equivalent to those produced in monkey cones as the
      animals view fruit. Three different viewing conditions were examined involving
      variations in the relative luminances of fruit and leaves and the spectrum of the
      illuminant. In all cases, performance was best for simulated trichromacies
      including M/L pigments with the largest spectral separation. Thus, the inequality
      of opsin gene frequency in Callitrichid monkeys may reflect adaptive pressures.

PMID- 15518193
TI  - Photoreceptor topography and cone-specific electroretinograms.
AB  - It is implicit in many cone-specific ERG studies that the amplitude is
      proportional to the numbers of cones stimulated. The objective of these
      experiments was to test this idea by comparing ERGs obtained from different areas
      of the retina with histological data on cone-density distributions. The histology
      (Curcio et al., 1990) shows that the cumulative number of cones in the human
      retina increases exponentially with stimulus diameter between 0- and 40-deg
      eccentricity. L-, M-, and (L+M) cone-driven 30-Hz ERGs were obtained from a
      series of stimuli with one of the following configurations: (1) Circular stimuli
      of different angular subtense up to 70-deg diameter. (2) Annuli with 70-deg outer
      diameter but variable inner diameter. (3) Annuli of constant area but increasing
      eccentricity. Cone contrasts were equalized for each stimulus condition. The
      modulated and nonmodulated regions of the screen had the same mean hue and
      luminance. The data suggest that the L+M cone ERG amplitude increases with
      stimulus diameter in direct proportion to the estimated number of cones
      stimulated. Furthermore, the total L+M responses appear to be predicted from
      individual L and M responses by simple linear summation for both the disc and
      annular stimuli.

PMID- 15518192
TI  - Cone visual pigments of the Australian marsupials, the stripe-faced and fat
      tailed dunnarts: sequence and inferred spectral properties.
AB  - Studies of color vision in marsupial mammals have been very limited. Two
      photoreceptor genes have been characterized from the tammar wallaby, but a third
      cone pigment was suggested by microspectrophotometric measurements on cone
      photoreceptors in two other species, including the fat-tailed dunnart,
      Sminthopsis crassicaudata. To determine the sequence and infer absorption maxima
      of the cone photoreceptor pigments of S. crassicaudata and the related stripe
      faced dunnart (Sminthopsis macroura), we have used evolutionarily conserved
      sequences of the cone pigments of other species, including the tammar wallaby, to
      design primers to amplify the S. macroura and S. crassicaudata pigment sequences
      by the polymerase chain reaction (PCR) using genomic DNA or retinal cDNA as a
      template. These primers will be useful for amplifying cone opsin coding sequences
      from a variety of vertebrates. Amplified products were directly sequenced to
      determine gene structure and coding sequences. The inferred amino acid sequences
      of the cone visual pigments indicated that both species have middle-wave
      sensitive (MWS) pigments with a predicted absorption maximum (lambda(max)) at 530
      nm, and ultraviolet-sensitive (UVS) pigments with a predicted lambda(max) at 360
      nm. The MWS pigments of the two species differ by two, and UVS by three amino
      acid positions. No evidence was obtained for a third cone pigment in either
      species.

PMID- 15518195
TI  - Induced contrast asynchronies may be useful for luminance photometry.
AB  - Shapiro et al. (2004) introduced a new visual effect (the induced contrast
      asynchrony) that demonstrates a perceptual separation between the response to a
      modulated light and the response to contrast of the light relative to background.
      The effect is composed of two physically identical disks, one surrounded by a
      dark annulus and the other by a light annulus. The luminance levels of both
      central disks were modulated in time, producing a stimulus with in-phase
      luminance modulation and antiphase contrast modulation. Observers primarily
      perceived the disks to be modulating asynchronously (i.e. they perceived the
      contrast), but at low temporal frequencies could also track the luminance level.
      Here we document that the induced contrast asynchrony disappears when the
      surrounds are achromatic and the center lights are modulated near the
      equiluminant axis. Observers viewed 1-deg-diameter disks embedded 2-deg-diameter
      achromatic surrounds. The chromaticity of the disks was modulated in time (1 Hz)
      along lines in an S versus Luminance cardinal color plane and an L-M versus
      Luminance cardinal color plane; observers responded as to whether the modulation
      appeared in phase. For all observers and both color planes, the lights appeared
      in phase most frequently at angles near the standard observer's equiluminant line
      and out of phase at angles further away from that line. Observers differed in the
      range of angles that produce the appearance of in-phase modulation. The results
      suggest that induced contrast asynchronies may be useful as a technique for
      equating luminance of disparate lights.

PMID- 15518194
TI  - Effect of foveal tritanopia on reaction times to chromatic stimuli.
AB  - To investigate the effect of foveal inhomogeneities on sensitivity to chromatic
      stimuli, we measured simple reaction times (RTs) and detection thresholds to
      temporally and spatially blurred isoluminant stimuli at retinal eccentricities
      from 0 deg to 8 deg. Three color-normal subjects participated. Contrast gain was
      derived from the slope of the RT versus contrast function. With a Gaussian
      spatial distribution (S.D. = 0.5 deg) and modulation between white (CIE x, y, L =
      0.31, 0.316, 12.5 cd x m(-2)) and blue (MBDKL 90 deg), gain was maximal at about
      2-deg eccentricity and declined by approximately 1 log unit towards the center
      and the periphery. The red (0 deg) and green (180 deg) cardinal axes showed
      maximum gain in the center, whilst the yellow (270 deg) data were intermediate.
      Although the spatial extent of the Gaussian spot was much larger than the S-cone
      free zone, we wished to determine whether foveal tritanopia was responsible for
      the marked drop in sensitivity to the 90-deg stimulus. To align the color vector
      along a tritan line, we used a smaller disk (0.3 deg) with a blurred edge and
      measured detection threshold, rotating the vector until minimum central
      sensitivity was obtained. Other workers have used transient tritanopia or
      minimally distinct border to similar effect. By repeating this at different
      locations in color space, a group of vectors were obtained. These converged near
      to the S-cone co-punctal point, evidence that they lay along tritan confusion
      lines. These threshold findings were then confirmed using the RT-derived contrast
      gain function. The tritan vectors were less pronounced as stimulus size
      increased. With the vector optimized to produce foveal tritanopia, the RT gain
      versus eccentricity functions for the 90-deg and 270-deg stimuli both fell
      markedly in the center and periphery, and sensitivity peaked at about 3-deg
      eccentricity. There are some similarities between these findings and the
      underlying photoreceptor distributions. As a result, there is a greater
      difference in gain between red-green and blue-yellow systems in the center than
      in the near periphery. We conclude that the RT versus contrast function is a
      sensitive index of foveal opponency.

PMID- 15518196
TI  - Multifocal electroretinogram in trichromat and dichromat observers under cone
      isolating conditions.
AB  - The aim of this study was to obtain information about single cone class driven
      activity in the inner and outer retina in humans. We examined outer retinal
      activity with the multifocal electroretinogram (mfERG) and inner retinal activity
      using multifocal oscillatory potentials (mfOPs). A standard (black-white)
      stimulus was used, as well as stimuli aimed at isolating a single photoreceptor
      class. The results of 10 trichromats were compared to those of 2 protanopes and 2
      deuteranopes. At both retinal layers we find that trichromats show cone isolating
      response amplitudes that reflect the expected number of cones and that single-
      gene dichromats have a similar total number of functioning cones as trichromats.
      The ratio of the responses of the L- and M-cones is slightly smaller for the
      mfOPs than for the mfERGs. The results indicate that there are major changes in
      the gain of retinal signals after the inner plexiform layer.

PMID- 15518197
TI  - Generality of rod hue biases with smaller, brighter, and photopically specified
      stimuli.
AB  - This study tests the generality of previously demonstrated rod hue biases (red
      and blue biases at shorter wavelengths and a green bias at longer wavelengths)
      that cause the loci of the three spectral unique hues to shift to longer
      wavelengths. We found rod hue biases for 2-deg targets to be generally similar in
      magnitude and light-level dependence to those observed for 7.4-deg targets (the
      size most often studied) when measured at 7-deg eccentricity. The largest effects
      for both test sizes occurred at the lowest light levels tested, 1 log scotopic
      troland. All three rod hue biases were found with 0.6-deg targets, but were not
      reliably measurable at the lowest light levels and were reduced in magnitude and
      consistency across observers. The largest rod hue biases all occurred at the same
      scotopic light level, which corresponds to different photopic light levels for
      the three hue biases, because of differences in photopic and scotopic spectral
      sensitivity. This suggests that no single photopic light level will produce such
      large effects for all three rod hue biases. Finally, when the rod influence on a
      specific unique-hue locus was measured using photopically (rather than
      scotopically) constant stimuli, rod hue biases were still found but were more
      variable in magnitude and incidence across observers. We conclude that the rod
      hue biases we have previously described can be found with smaller stimuli, at
      somewhat higher light levels, and under photopically constant conditions,
      although our prior conditions tend to produce larger, more reliable rod hue
      biases.

PMID- 15518198
TI  - Photostimulator allowing independent control of rods and the three cone types.
AB  - This report describes a second-generation photostimulator with four primary
      lights that allows independent control of the stimulation of the four receptor
      types in the human eye. The new design uses LEDs (with light levels controlled by
      eight drivers that include voltage-to-frequency converters that provide 1-micros
      pulses at frequencies up to 250 kHz), with four center channels being combined by
      use of a fiber optic assembly, and likewise for four surround channels. Four
      fiber optic bundles are merged into a single bundle whose output is fed into a
      spatial homogenizer terminated by a diffuser. An interference filter is
      sandwiched between each LED and the fiber optic bundle. Two camera lenses
      collimate light from the diffusers, one for center and one for surround. The
      center-surround field configuration is formed by a photometric cube with a
      mirrored ellipse on the hypotenuse. A field lens places images of the diffusers
      in the plane of an artificial pupil. The fields are highly uniform. Following
      alignment and calibration, the center and surround fields are indistinguishable.
      An observer calibration procedure, designed to compensate for prereceptoral
      filtering, is shown by calculation to correct also for normal observer receptoral
      spectral sensitivity variation. With the instrument calibrated for the individual
      observer, a peripherally fixated 200-ms 40% contrast rod center field pulse,
      highly conspicuous under dark adaptation, is invisible following light
      adaptation.

PMID- 15518199
TI  - Masking of grating detection in the isoluminant plane of DKL color space.
AB  - A novel noise-masking technique was used to test D'Zmura and Knoblauch's (1998)
      idea that subjects employ off-channel looking in detecting chromatic test stimuli
      embedded in spatiotemporal chromatic noise. Detection thresholds were obtained
      for stationary, isoluminant, Gaussian-windowed (sigma(x) = sigma(y) = 2.25 deg;
      sigma(t) = 0.25 s), 135 deg (yellow/blue) or 160 deg (orange/blue-green),
      sinusoidal test gratings (11 deg x 11 deg; 0.75 cycle/deg) superimposed on each
      of a series of dynamic, random-check chromatic noise masks varying in azimuth in
      DKL space. Thresholds for detecting the test in the presence of these variable
      masks were again measured in the presence of an additional (auxiliary) noise mask
      created from colors falling on azimuths of 0 deg or 90 deg (135-deg test) or 0
      deg or 135 deg (160-deg test). The effectiveness, k(var), of the variable noise
      masks in elevating grating detection thresholds was determined by fitting the
      detection data to the Pelli-Legge equation relating test detection energy to
      variable noise-mask energy: E(t) = K + k(var)N(var). Differences in the
      calculated values of k(var) for detection data obtained with and without the
      auxiliary masks were consistent with off-channel looking and were well accounted
      for by a simple model based on the idea that subjects possess a multichannel
      array of linear chromatic detectors spanning the isoluminant plane of DKL space,
      and they can choose the channel that has the highest signal-to-noise ratio.

PMID- 15518200
TI  - Chromatic adaptation, perceived location, and color tuning properties.
AB  - We have studied the influence of chromatic adaptation upon the perceived visual
      position of a test stimulus using a Vernier alignment task. Maximum and minimum
      offsets in spatial position are generated when the adapting and test stimuli lie
      on the same and orthogonal axes in MBDKL color space, respectively. When the test
      stimuli lie on intermediate color axes, the measured positional shifts decrease
      as a function of the angular separation in color space (phi) from the adapting
      stimulus. At low stimulus contrasts, these shifts follow a sinusoidal function of
      phi and exhibit broad chromatic tuning and can be accounted for by a model in
      which the centroid is extracted from the linear combination of after-image,
      formed by the adapting stimulus, and the test stimulus. Such linear, broadband
      behavior is consistent with the response properties of chromatic neurons in the
      precortical visual pathway. At high contrast, and when adaptation gets closer to
      the S/(L+M) axis, the tuning functions become narrower and require sinusoids
      raised to increasingly higher exponents in order to describe the data. This
      narrowing of chromatic tuning is consistent with the tuning properties of
      chromatic neurons in the striate cortex, and implies the operation of a nonlinear
      mechanism in the combination of cone outputs.

PMID- 15518201
TI  - Perceptual classification of chromatic modulation.
AB  - We measured the regions of the equiluminant plane that are exploited by observers
      during a Yes/No detection task. The signal was a 640-ms Gaussian modulation
      (sigma(t) = 160 ms) of a Gaussian spatial patch (sigma(s) = 2.4 deg) presented in
      chromatically bivariate uniform noise. One component of the noise was along the
      direction axial with the signal in color space, the other perpendicular. Four
      signal directions were tested: along cardinal LM and S axes and two intermediate
      directions to which the cardinal axes were equally sensitive. The distribution of
      noise chromaticities from each trial was correlated with the observers' responses
      and the presence and absence of the signal to build a classification image of the
      distribution of chromaticities on which the decision of the observer was based.
      The images show a narrowly selective peak in the signal direction flanked by
      regions with a broader selectivity. These results raise the possibility that
      detection judgments are mediated by both linear and nonlinear mechanisms with
      peak sensitivities between the cardinal directions.

PMID- 15518202
TI  - Chromatic contrast detection in spatial chromatic noise.
AB  - The spectral properties of chromatic-detection mechanisms were investigated using
      a noise-masking paradigm. Contrast-detection thresholds were measured for a
      signal with a Gaussian spatial profile, modulated in the equiluminant plane in
      the presence of spatial chromatic noise. The noise was distributed within a
      sector in the equiluminant plane, centered on the signal direction. Each stimulus
      consisted of two adjacent fields, one of which contained the signal, separated
      horizontally by a gap with the same average chromaticity as the uniform
      background. Observers were asked to judge on which side of the central fixation
      point the signal was displayed via a two-alternative, forced-choice (2AFC)
      paradigm. Contrast thresholds were measured for four color directions and three
      sector widths at increasing levels of the average energy of the axial component
      of the noise. Results show that contrast thresholds are unaffected by the width
      of the noise sector, as previously found for temporally modulated stimuli
      (D'Zmura & Knoblauch, 1998). The results are consistent with the existence of
      spectrally broadband linear-detection mechanisms tuned to the signal color
      direction and support the hypothesis of the existence of higher-order color
      mechanisms with sensitivities tuned to intermediate directions in color space.

PMID- 15518203
TI  - Color mechanisms used in selecting stimuli for attention and making
      discriminations.
AB  - Previous work (Nagy & Thomas, 2003) showed that signals in different Cardinal
      color mechanisms could be combined to facilitate search for a color target.
      Further investigation (Nagy et al., 2003) suggested that signals in one Cardinal
      color mechanism were used to select a subset of stimuli to be attended, while
      signals in second Cardinal mechanism were used to discriminate the stimuli within
      the selected subset. In the studies described below, we asked if observers could
      use color mechanisms tuned to directions other than the Cardinal directions to
      select and discriminate stimuli. Observers searched for a single target stimulus
      that differed in chromaticity from nine distractor stimuli. A two-alternative
      forced-choice procedure was used to estimate thresholds. Results were consistent
      with the hypothesis that color mechanisms tuned to many different directions in
      color space mediate discrimination, but suggest that only signals in Cardinal
      mechanisms can be used to select stimuli for attention. Results imply that the
      selection of stimuli for attention on the basis of color may be mediated at the
      level of the lateral geniculate nucleus (LGN).

PMID- 15518204
TI  - Long-term renormalization of chromatic mechanisms following cataract surgery.
AB  - The optical density of the human crystalline lens progressively increases with
      age, the greatest increase in the visible spectrum being at short wavelengths.
      This produces a gradual shift in the spectral distribution of the light reaching
      the retina, yet color appearance remains relatively stable across the life span,
      implying that the visual system adapts to compensate for changes in spectral
      sensitivity. We explored properties of this adaptive renormalization by measuring
      changes in color appearance following cataract surgery. When the lens is removed,
      cataract patients often report a large perceptual shift in color appearance that
      can last for months. This change in color appearance was quantified for four
      cataract patients (63-84 years) by determining the chromaticity of stimuli that
      appeared achromatic before surgery, and at various intervals after surgery for up
      to 1 year. Stimuli were presented on a calibrated CRT as 9.5-deg spots, with 3-s
      duration and 3-s interstimulus intervals (ISIs). Chromaticity was adjusted by the
      subjects in CIE L*a*b* color space with luminance fixed at 32 cd/m2, on a dark
      background. We also estimated the optical density of the cataractous lens by
      comparing absolute scotopic thresholds from 410 nm to 600 nm before and after
      surgery. The results demonstrated that immediately following surgery there is a
      large increase in the short-wave light reaching the retina, mainly below 500 nm.
      The achromatic settings generally showed an initial large shift in the "yellow"
      direction after surgery that gradually (but never fully) returned to the original
      achromatic point before surgery. The shifts in the achromatic point occur over a
      number of months and appear to occur independently of the fellow eye.

PMID- 15518205
TI  - Chromatic input to cells of the magnocellular pathway: mean chromaticity and the
      relative phase of modulated lights.
AB  - If the relative phase of red and green modulated lights is changed, at low
      temporal frequencies the response of cells of the magnocellular (MC) pathway has
      been found to be minimal not to counterphase, chromatic modulation (as expected
      of a luminance mechanism) but shifted to some phase intermediate between
      luminance and chromatic modulation. The results could only be modeled by assuming
      interaction between achromatic and chromatic inputs to MC cells. The 'phase
      shift' resembled that seen with psychophysical threshold measurements using the
      same stimuli. Psychophysical results also showed that the phase shift is
      dependent on the chromaticity of a background. The results reported here show
      that the direction of the phase shift in MC cells is reversed by changing the
      background from long to short wavelengths and is consistent with psychophysical
      observations. Cell behavior was again modeled by assuming vector summation of
      achromatic and chromatic inputs. The reversal of phase-shift direction requires a
      reversal in polarity of the chromatic input. The underlying physiological
      mechanism may involve summation of chromatic signals of opposite polarity; if the
      relative size of these signals depends on the background, this may determine the
      direction of phase shift.

PMID- 15518206
TI  - A single mechanism for both luminance and chromatic grating vernier tasks:
      evidence from temporal summation.
AB  - Vernier thresholds are determined by luminance rather than chromatic contrast
      when both are present in vernier targets. The role of luminance and chromatic
      mechanisms in vernier performance under equiluminant conditions remains
      uncertain. Temporal summation functions for vernier thresholds with luminance and
      red-green equiluminant gratings were compared to those for detection thresholds
      with similar stimuli. Vernier thresholds showed similar temporal summation for
      luminance and chromatic gratings, which is consistent with a single mechanism
      underlying vernier performance in the two conditions. However, detection
      thresholds showed a shorter temporal summation duration for luminance gratings
      than for chromatic gratings, which suggests that two different mechanisms
      underlie detection thresholds. Analysis of physiological data supports the
      hypothesis that the frequency-doubled response of ganglion cells in the
      magnocellular pathway can provide accurate spatiotemporal information for vernier
      performance at equiluminance.

PMID- 15518207
TI  - Inferred retinal mechanisms mediating illusory distortions.
AB  - The Zoellner illusion is a geometric distortion occurring when nonorthogonal
      inducing lines appear to tilt veridically parallel bars. The retinal pathways
      contributing to such illusions are unknown. The goal of this experiment was to
      investigate the retinal origin of the illusion. This was accomplished by
      determining the contrast gain for illusion thresholds. The magnocellular (MC-)
      and parvocellular (PC-) pathways exhibit different contrast gains, and this
      difference can be used psychophysically to identify the pathway. The stimulus
      pattern was four vertical bars with a series of inducing lines. The bars were
      always 5% higher in contrast than the inducing bars. The pattern was presented on
      a larger pedestal. Two paradigms were used. In the pulsed-pedestal paradigm, the
      observer adapted to the background and the pedestal and pattern were presented
      together as a brief pulse. In the steady-pedestal paradigm, the observer adapted
      to the continuously presented pedestal and the pattern appeared as a brief pulse.
      The contrast between the pedestal and the pattern was varied to obtain thresholds
      for two criteria: perceiving the directions of the inner inducing lines, and
      perceiving the distortion of the bars. The results for both criteria were similar
      in shape, but displaced in sensitivity. Detection of the directions of the inner
      inducing lines was 0.16-0.29 log unit more sensitive than perception of the
      illusion. The data for the pulsed-pedestal paradigm depended on the contrast
      between the pedestal and the pattern and produced a shallow V-shape. These
      results were associated with mediation in the PC-pathway. The data for the steady
      pedestal paradigm depended on the pedestal luminance in a linear relation and
      showed similar sensitivity to the data for the pulsed-pedestal paradigm.
      Perception of the illusion required 10-15% Weber contrast.

PMID- 15518208
TI  - Influence of motion on chromatic detection.
AB  - Intense scrutiny has been focused on whether chromatic stimuli contribute to
      motion perception. The present study considers a related but different question:
      how does motion affect chromatic detection? Detection thresholds were measured
      for a disk that underwent a brief (13.3 ms) chromatic change in the L/(L+M)
      chromatic direction. The disk's presentation sequence and speed (0-16 deg/s) were
      manipulated. In the coherent presentation sequence, the disk moved smoothly along
      a circular path centered on the fixation point. In the random presentation
      sequence, the disk appeared randomly at positions along the circular path. In
      both types of sequences, the disk underwent a brief chromatic change midway
      through the temporal presentation sequence. Threshold was elevated in the
      coherent condition compared to the random condition, and threshold decreased with
      an increase in speed. The threshold elevation observed in the coherent
      presentation sequence can be accounted for by temporal integration. The decrease
      in threshold with an increase in speed can be accounted for by spatial
      integration. The results, therefore, can be explained by spatiotemporal
      integration, without invoking a neural mechanism specialized for motion.

PMID- 15518209
TI  - Information limits on neural identification of colored surfaces in natural
      scenes.
AB  - If surfaces in a scene are to be distinguished by their color, their neural
      representation at some level should ideally vary little with the color of the
      illumination. Four possible neural codes were considered: von-Kries-scaled cone
      responses from single points in a scene, spatial ratios of cone responses
      produced by light reflected from pairs of points, and these quantities obtained
      with sharpened (opponent-cone) responses. The effectiveness of these codes in
      identifying surfaces was quantified by information-theoretic measures. Data were
      drawn from a sample of 25 rural and urban scenes imaged with a hyperspectral
      camera, which provided estimates of surface reflectance at 10-nm intervals at
      each of 1344 x 1024 pixels for each scene. In computer simulations, scenes were
      illuminated separately by daylights of correlated color temperatures 4000 K, 6500
      K, and 25,000 K. Points were sampled randomly in each scene and identified
      according to each of the codes. It was found that the maximum information
      preserved under illuminant changes varied with the code, but for a particular
      code it was remarkably stable across the different scenes. The standard deviation
      over the 25 scenes was, on average, approximately 1 bit, suggesting that the
      neural coding of surface color can be optimized independent of location for any
      particular range of illuminants.

PMID- 15518210
TI  - Minimum-variance cone-excitation ratios and the limits of relational color
      constancy.
AB  - Relational color constancy refers to the constancy of the perceived relations
      between the colors of surfaces of a scene under changes in the spectral
      composition of the illuminant. Spatial ratios of cone excitations provide a
      natural physical basis for this constancy, as, on average, they are almost
      invariant under illuminant changes for large collections of natural surfaces and
      illuminants. The aim of the present work was to determine, computationally, for
      specific surfaces and illuminants, the constancy limits obtained by the
      application of a minimum-variance principle to cone-excitation ratios and to
      investigate its validity in predicting observers' surface-color judgments. Cone
      excitations and their changes due to variations in the color of the illuminant
      were estimated for colored surfaces in simulated two-dimensional scenes of
      colored papers and real three-dimensional scenes of solid colored objects. For
      various test surfaces, scenes, and illuminants, the estimated levels of
      relational color constancy mediated by cone-excitation ratios varied
      significantly with the test surface and only with certain desaturated surfaces
      corresponded to ideal matches. Observers' experimental matches were compared with
      predictions expressed in CIE 1976 (u',v') space and were found to be generally
      consistent with minimum-variance predictions.

PMID- 15518211
TI  - Color constancy by asymmetric color matching with real objects in three
      dimensional scenes.
AB  - Color matching experiments use, in general, stimuli that are poor representations
      of the natural world. The aim of this work was to compare the degree of color
      constancy for a range of illuminant pairs using a new matching technique that
      uses both real objects and three-dimensional (3-D) real scenes. In the
      experiment, observers viewed a 3-D real scene through a large beamsplitter that
      projects on the right-hand side of the scene (match scene), the virtual image of
      a 3-D object (match object) such it appeared part of the scene. On the left-hand
      side of the scene (test scene), observers viewed a symmetrical scene containing a
      test object identical to the match object. Test and match objects were both
      surrounded by the same reflectances with identical spatial arrangement. The
      illuminant on the test scene had always a correlated color temperature of 25,000
      K. The illuminant on the match scene could be any of seven different illuminants
      with correlated color temperatures in the range 25,000 K-4000 K. In each trial,
      the observers, who were instructed to perform surface color matches, adjusted the
      illuminant on the match object. Constancy indices were very high (0.81-0.93),
      varied with the color of the match object, and increased with the extent of the
      illuminant change. Observer's mismatches, however, were independent of the extent
      of the illuminant change.

PMID- 15518212
TI  - Protanopic observers show nearly normal color constancy with natural reflectance
      spectra.
AB  - The ability of color-deficient observers to discriminate between illuminant
      changes and surface-reflectance changes in a scene was tested with natural and
      Munsell reflectance spectra. To avoid the confounding effects of spatial
      structure, stimuli were simulations of Mondrian-like colored patterns, presented
      on a computer-controlled color monitor. Protanopes performed less well than
      normal trichromats, regardless of the type of reflectance spectra, but they were
      least disadvantaged with patterns comprising reflectance spectra drawn from urban
      and rural scenes, more characteristic of the natural environment.

PMID- 15518213
TI  - Brightness induction: unequal spatial integration with increments and decrements.
AB  - Modern theories of brightness induction include an influence from regions that do
      not share a border with the target. This study tested whether the spatial range
      of neural integration is the same with incremental versus decremental contrast
      edges in relatively remote parts of the background. Using an asymmetric matching
      task, observers set the brightness of a comparison ring, within its own uniform
      surround, to match the brightness of a test ring within a contiguous surround and
      a noncontiguous background. The measurements showed that the area of integration
      depended on the incremental versus decremental contrast polarity at the edge
      between the surround and background. This implies that brightness induction from
      an inhomogeneous background must consider the polarity of contrast edges within
      the whole scene.

PMID- 15518214
TI  - Chromatic and contrast selectivity in color contrast adaptation.
AB  - We used color contrast adaptation to examine the chromatic and contrast
      selectivity of central color mechanisms. Adaptation to a field whose color varies
      along a single axis of color space induces a selective loss in sensitivity to the
      adapting axis. The resulting changes in color appearance are consistent with
      mechanisms formed by different linear combinations of the cone signals. We asked
      whether the visual system could also adjust to higher-order variations in the
      adapting stimulus, by adapting observers to interleaved variations along both the
      L versus M and the S versus LM cardinal axes. The perceived hue of test stimuli
      was then measured with an asymmetric matching task. Frequency analysis of the hue
      shifts revealed weak but systematic hue rotations away from each cardinal axis
      and toward the diagonal intermediate axes. Such shifts could arise if the adapted
      channels include mechanisms with narrow chromatic selectivity, as some
      physiological recordings suggest, but could also reflect how adaptation alters
      the contrast response function. In either case they imply the presence of more
      than two mechanisms within the chromatic plane. In a second set of measurements,
      we adapted to either the L versus M or the S versus LM axis alone and tested
      whether the changes in hue could be accounted for by changes in relative contrast
      along the two axes. For high contrasts the hue biases are larger than the
      contrast changes predict. This dissociation implies that the contrast and hue
      changes are not carried by a common underlying signal, and could arise if the
      contrast along a single color direction is encoded by more than one mechanism
      with different contrast sensitivities or if different subsets of channels encode
      contrast and hue. Such variations in contrast sensitivity are also consistent
      with physiological recordings of cortical neurons.

PMID- 15518215
TI  - Flashing anomalous color contrast.
AB  - A new visual phenomenon that we call flashing anomalous color contrast is
      described. This phenomenon arises from the interaction between a gray central
      disk and a chromatic annulus surrounded by black radial lines. In an array of
      such figures, the central gray disk no longer appears gray, but assumes a color
      complementary to that of the surrounding annulus. The induced color appears: (1)
      vivid and saturated; (2) self-luminous, not a surface property; (3) flashing with
      eye or stimulus movement; (4) floating out of its confines; and (5) stronger in
      extrafoveal than in foveal vision. The strength of the effect depends on the
      number, length, width, and luminance contrast of the radial lines. The results
      suggest that the chromatic ring bounding the inner tips of the black radial lines
      induces simultaneous color contrast, whereas the radial lines elicit, in
      conjunction with the gray disk and the ring, the flashing, vividness, and high
      saturation of the effect. The stimulus properties inducing the illusion suggest
      that flashing anomalous color contrast may be based on asynchronous interactions
      among multiple visual pathways.

PMID- 15518216
TI  - Chromatic assimilation unaffected by perceived depth of inducing light.
AB  - Chromatic assimilation is a shift toward the color of nearby light. Several
      studies conclude that a neural process contributes to assimilation but the neural
      locus remains in question. Some studies posit a peripheral process, such as
      retinal receptive-field organization, while others claim the neural mechanism
      follows depth perception, figure/ground segregation, or perceptual grouping. The
      experiments here tested whether assimilation depends on a neural process that
      follows stereoscopic depth perception. By introducing binocular disparity, the
      test field judged in color was made to appear in a different depth plane than the
      light that induced assimilation. The chromaticity and spatial frequency of the
      inducing light, and the chromaticity of the test light, were varied. Chromatic
      assimilation was found with all inducing-light sizes and chromaticities, but the
      magnitude of assimilation did not depend on the perceived relative depth planes
      of the test and inducing fields. We found no evidence to support the view that
      chromatic assimilation depends on a neural process that follows binocular
      combination of the two eyes' signals.

PMID- 15518217
TI  - Interactions of chromaticity and luminance in edge identification depend on
      chromaticity.
AB  - The goal of this work was to study interactions of chromaticity and luminance in
      edge identification. Two horizontal spatial sawtooth patterns, one with positive
      and the other with negative harmonics, were compared in a two-alternative forced
      choice (2-AFC) procedure. The observer identified which pattern had sharp upper
      or lower edges. The fundamental frequency was 2 cycles/deg (cpd), with 5 cycles
      presented in a 2.5-deg square field. The pattern was presented as a 1-s raised
      temporal cosine, replacing part of an 8-deg background. Stimuli were specified in
      a cone troland (l, s, Y) chromaticity space, with correction for individual
      equiluminance at a nominal 115 td, and individual tritan direction. A preliminary
      set of interleaved staircases established edge identification for the six
      directions of the (l, s, Y) space. Three compound stimuli combining two
      orthogonal directions were chosen and included with the end-points in five
      randomly interleaved staircases. For combinations of Y with l-chromaticity, or l-
      with s-chromaticity, probability summation was observed. Combinations of Y with s
      chromaticity revealed opponency. Data for +s, +Y and -s, -Y were subadditive;
      data for +s, -Y and -s, +Y were additive. Control studies using detection rather
      than edge identification revealed probability summation for all combinations.
      Luminance edges did not enhance stimuli with l-chromaticities. There was an
      interaction of luminance edges with s-chromaticities. Dim "blues" and bright
      "yellows" showed linear summation. Bright "blues" and dim "yellows" showed
      opponency.

PMID- 15518218
TI  - Changes in color appearance caused by perceptual grouping.
AB  - How is chromatic induction affected by perceptual grouping? Chromatic induction
      has been studied extensively, as has grouping, but only a small number of
      experiments have connected them. Even fewer reports go beyond weakly controlled
      qualitative observations. We report here a new and substantial color shift caused
      by perceptual grouping: a shift in appearance due to chromatic induction in one
      part of the visual field occurs also in a separate region that belongs to the
      same group. The color appearance of a test square within various surrounds was
      measured by asymmetric matching. The test square was at the center of an
      "hourglass" structure formed by other elements in the surround. The test shifted
      in color appearance toward the appearance of these other elements, whose color
      was affected by local chromatic induction. Control experiments ruled out as
      explanations (1) direct chromatic induction from the other elements into the test
      area, and (2) the influence of background light occluded by introducing the
      elements forming the hourglass.

PMID- 15518219
TI  - Infant color vision: influence of surround chromaticity on spontaneous looking
      preferences.
AB  - When infants are tested with stimuli of various chromaticities embedded in a dark
      or achromatic (white) surround, they show maximal preference for stimuli of
      maximal colorimetric purity, and minimal preference for achromatic stimuli. We
      investigated how this pattern of preferences changes with changes of surround
      chromaticity. Sixteen-week-old infants were tested in two experimental
      conditions. The surrounds in the first condition were red and white; and in the
      second condition green and white. The three test stimuli varied in colorimetric
      purity from white to red in the first condition, and from white to green in the
      second condition. A test stimulus that appeared achromatic to adults when viewed
      in the chromatic surround was included. Infant spontaneous looking preferences
      changed with changes of surround chromaticity. The changes were consistent with
      the conclusion that infant looking behavior is governed by a preference for the
      stimuli that differ maximally in purity from the surround. The implications of
      this pattern of results are discussed.

PMID- 15518220
TI  - Infants' spontaneous color preferences are not due to adult-like brightness
      variations.
AB  - In the present work, we explore the perceptual bases of infants' spontaneous
      looking preferences among isoluminant chromatic stimuli (Bornstein, 1975). Three
      experiments were conducted. In Experiment 1, adult subjects made brightness
      matches between a white standard and each of six isoluminant chromatic stimuli.
      The classic variations of brightness with chromaticity were found. In Experiment
      2, 12-week-old infants' spontaneous looking preferences were measured for white
      lights of different luminances. Preference increased with increasing luminance,
      suggesting that brightness differences are sufficient to create looking
      preferences among isochromatic stimuli. In Experiment 3, infants' preferences
      were tested for each of the six chromatic stimuli paired against white, at both
      isoluminance and (adult) isobrightness. All chromatic stimuli were preferred to
      white, and the pattern of preferences was similar for both isoluminance and
      isobrightness conditions. It is concluded that hue and/or saturation, rather than
      brightness, control infants' spontaneous looking preferences among chromatic
      stimuli.

PMID- 15518221
TI  - Luminance-dependent hue shift in protanopes.
AB  - For normal trichromats, the hue of a light can change as its luminance varies.
      This Bezold-Brucke (B-B) hue shift is commonly attributed to nonlinearity in the
      blue-yellow opponent system. In the present study, we questioned whether
      protanopes experience analogous changes. Two protanopes (Ps) viewed spectral
      lights at six luminance levels across three log steps. Two normal trichromats
      (NTs) were tested for comparison. A variant of the color-naming method was used,
      with an additional "white" term. To overcome the difficulty of Ps' idiosyncratic
      color naming, we converted color-naming functions into individual color spaces,
      by way of interstimulus similarities and multidimensional scaling (MDS). The
      color spaces describe each stimulus in terms of spatial coordinates, so that hue
      shifts are measured geometrically, as displacements along specific dimensions.
      For the NTs, a B-B shift derived through MDS agreed well with values obtained
      directly by matching color-naming functions. A change in color appearance was
      also observed for the Ps, distinct from that in perceived brightness. This change
      was about twice as large as the B-B shift for NTs and combined what the latter
      would distinguish as hue and saturation shifts. The protanopic analogue of the B
      B shift indicates that the blue-yellow nonlinearity persists in the absence of a
      red-green signal. In addition, at mesopic levels (< or = 38 td), the Ps' MDS
      solution was two dimensional at longer wavelengths, suggesting rod input.
      Conversely, at higher luminance levels (76 td-760 td) the MDS solution was
      essentially one dimensional, placing a lower limit on S-cone input at longer
      wavelengths.

PMID- 15518222
TI  - Color and language: worldwide distribution of Daltonism and distinct words for
      "blue".
AB  - A geographical review of the published literature confirmed that red-green color
      vision deficiency (Daltonism) is rare near the equator and more prevalent at
      higher latitudes, as others have reported. A survey of dictionaries of the
      languages spoken by the populations for which Daltonism data are available
      confirmed that distinct words for "blue" are also rare near the equator, and more
      common at higher latitudes. These results were compared to show an even stronger
      relation between the proportion of languages with a word for "blue" and the
      prevalence of Daltonism. We believe that the strong correlation between "blue"
      and Daltonism suggests that an evolutionary, physiological cause for both
      phenomena.

PMID- 15518223
TI  - Clinical heterogeneity between two Japanese siblings with congenital
      achromatopsia.
AB  - Congenital achromatopsia is a stationary retinal disorder with autosomal
      recessive inheritance. It is characterized by significant attenuation of cone
      photoreceptor function. Symptoms include photophobia, nystagmus, and poor visual
      acuity from birth. Unlike in cone or cone-rod dystrophies, the retinal fundus
      usually appears normal. Here we describe two siblings with congenital
      achromatopsia, who exhibit different ophthalmic phenotypes. History was taken,
      and ophthalmic examinations were performed in a 7-year-old girl and her 5-year
      old brother, who were referred to our department because of poor visual acuity.
      Two of their grandparents were brother and sister, suggesting an autosomal
      recessive transmission in inheritance. They have been followed for more than 13
      years since the initial evaluation. Symptoms, visual acuity, and kinetic visual
      field were very similar to each other, consistent with findings of typical
      congenital achromatopsia. However, color-vision tests suggested that the brother
      had residual color discrimination, but the sister did not. The siblings had
      different full-field electroretinographic and spectral-sensitivity findings:
      residual cone functions were detected in only the brother, in agreement with his
      residual color vision. They also had different findings of retinal fundi and
      ocular refractions: the sister had bilaterally atrophic-appearing macular lesions
      and myopic errors. In contrast, the brother remains hyperopia and has exhibited
      no specific retinal findings until age 18 years. The causes why both complete and
      incomplete achromats occur in the siblings are uncertain but might be caused by
      modifying effects of sex-related genes or by environmental factors influencing
      certain gene regulations in cone photoreceptors.

PMID- 15518224
TI  - Multifocal and full-field electroretinogram changes associated with color-vision
      loss in mercury vapor exposure.
AB  - We evaluated the color vision of mercury-contaminated patients and investigated
      possible retinal origins of losses using electroretinography. Participants were
      retired workers from a fluorescent lamp industry diagnosed with mercury
      contamination (n = 43) and age-matched controls (n = 21). Color discrimination
      was assessed with the Cambridge Colour Test (CCT). Retinal function was evaluated
      by using the ISCEV protocol for full-field electroretinography (full-field ERG),
      as well as by means of multifocal electroretinography (mfERG). Color-vision
      losses assessed by the CCT consisted of higher color-discrimination thresholds
      along the protan, deutan, and tritan axes and significantly larger discrimination
      ellipses in mercury-exposed patients compared to controls. Full-field ERG
      amplitudes from patients were smaller than those of the controls for the scotopic
      response b-wave, maximum response, sum of oscillatory potentials (OPs), 30-Hz
      flicker response, and light-adapted cone response. OP amplitudes measured in
      patients were smaller than those of controls for O2 and O3. Multifocal ERGs
      recorded from ten randomly selected patients showed smaller N1-P1 amplitudes and
      longer latencies throughout the 25-deg central field. Full-field ERGs showed that
      scotopic, photopic, peripheral, and midperipheral retinal functions were
      affected, and the mfERGs indicated that central retinal function was also
      significantly depressed. To our knowledge, this is the first demonstration of
      retinal involvement in visual losses caused by mercury toxicity.

PMID- 15518225
TI  - Evaluation of an updated HRR color vision test.
AB  - The HRR pseudoisochromatic plate (pip) test was originally designed as a
      screening and diagnostic test for color vision deficiencies. The original HRR
      test is now long out of print. We evaluate here the new 4th edition of the HRR
      test, produced in 2002 by Richmond Products. The 2002 edition was compared to the
      original 1955 edition for a group of subjects with normal color vision and a
      group who had been previously diagnosed as having color vision deficiencies. The
      color deficient subjects spanned the range of severity among people with red
      green deficiencies except for one individual who had a mild congenital tritan
      deficiency. The new test compared favorably with the original and in at least two
      areas, outperformed it. Among subjects with deutan defects the classification of
      severity correlated better with the anomaloscope results than the original; all
      the subjects who were classified as dichromats on the anomaloscope were rated as
      "severe" on the new HRR, while those diagnosed as anomalous trichromats were
      rated as mild or medium on the new test. Among those with moderate and severe
      defects the new test was highly accurate in correctly categorizing subjects as
      protan or deutan. In addition, a mild tritan subject made a tritan error on the
      new test whereas he was misdiagnosed as normal on the original.

PMID- 15518226
TI  - Colorimetric analysis of four editions of the Hardy-Rand-Rittler
      pseudoisochromatic tests.
AB  - At the Gottingen meeting of the International Colour Vision Society, I reported
      on a comparison of the second edition of the American Optical Hardy-Rand-Rittler
      Pseudoisochromatic plates (AO HRR) with the Richmond Products third edition of
      the same test and concluded that the chromaticities were exceptionally poorly
      matched and that the new edition was a "pale imitation of the real thing"
      (unpublished). This conclusion led to our abandoning a clinical trial. In 2002,
      Richmond Products has published a fourth edition and, in 2003, Waggoner has
      published a modified HRR with additional (Ishihara style) plates and the tetartan
      confusion figures removed. As a precursor to any clinical trial, the colors used
      in the plates have been measured and comparisons drawn between the four editions.
      While the two most recent editions much more closely resemble the original AO HRR
      and the chromaticities are much better aligned on the dichromatic confusion
      lines, the excitation purities (and therefore the degree of difficulty) of the
      plates are less well matched in the Richmond Products editions. In addition,
      there is a significant degree of metamerism in the third edition and Waggoner
      edition that makes variations in illuminant more critical to performance.

PMID- 15518227
TI  - Multidimensional scaling of D15 caps: color-vision defects among tobacco smokers?
AB  - Tobacco smoke contains a range of toxins including carbon monoxide and cyanide.
      With specialized cells and high metabolic demands, the optic nerve and retina are
      vulnerable to toxic exposure. We examined the possible effects of smoking on
      color vision: specifically, whether smokers perceive a different pattern of
      suprathreshold color dissimilarities from nonsmokers. It is already known that
      smokers differ in threshold color discrimination, with elevated scores on the
      Roth 28-Hue Desaturated panel test. Groups of smokers and nonsmokers, matched for
      sex and age, followed a triadic procedure to compare dissimilarities among 32
      pigmented stimuli (the caps of the saturated and desaturated versions of the D15
      panel test). Multidimensional scaling was applied to quantify individual
      variations in the salience of the axes of color space. Despite the briefness,
      simplicity, and "low-tech" nature of the procedure, subtle but statistically
      significant differences did emerge: on average the smoking group were
      significantly less sensitive to red-green differences. This is consistent with
      some form of injury to the optic nerve.

PMID- 15518228
TI  - Repeatability indices for the Farnsworth D-15 test.
AB  - The repeatability of the D-15 color-vision test is considered to be excellent.
      However, this conclusion is based on a subject pool which contained a large
      percentage of color-normals. This type of sampling could bias the repeatability
      results because color-normals rarely fail the test. Furthermore, color-normals
      usually do not perform the D-15 in the clinical setting. To establish the
      repeatability of the D-15 for a relevant clinical population, we examined the D
      15 results from two different sessions for 116 subjects who had a congenital red
      green color-vision defect. The kappa coefficient for intersession agreement
      indicated that approximately 84% of the subjects obtained the same pass/fail
      results at both sessions. The type of defect was repeatable on approximately 80%
      of the subjects. Although the repeatability of the D-15 for color-defective
      subjects was good, it was lower than the near-perfect agreement reported
      previously. The coefficients of repeatability for the crossings show that if a
      person makes less than five crossings then the test should be administered again
      in order to ensure that the test result is repeatable.

PMID- 15518229
TI  - Ability of the D-15 panel tests and HRR pseudoisochromatic plates to predict
      performance in naming VDT colors.
AB  - Color codes in VDT displays often contain sets of colors that are confusing to
      individuals with color-vision deficiencies. The purpose of this study is to
      determine whether individuals with color-vision deficiencies (color defectives)
      can perform as well as individuals without color-vision deficiencies (color
      normals) on a colored VDT display used in the railway industry and to determine
      whether clinical color-vision tests can predict their performance. Of the 52
      color defectives, 58% failed the VDT test. The kappa coefficients of agreement
      for the Farnsworth D-15, Adams desaturated D-15, and Richmond 3rd Edition HRR PIC
      diagnostic plates were significantly greater than chance. In particular, the D-15
      tests have a high probability of predicting who fails the practical test.
      However, all three tests had an unacceptably high false-negative rate (9.5-35%);
      so that a practical test is still needed.

PMID- 15518230
TI  - FDA regulation of labeling and promotional claims in therapeutic color vision
      devices: a tutorial.
AB  - The Food and Drug Administration (FDA) is responsible for determining whether
      medical device manufacturers have provided reasonable assurance, based on valid
      scientific evidence, that new devices are safe and effective for their intended
      use before they are introduced into the U.S. market. Most existing color vision
      devices pose so little risk that their manufacturers are not required to submit a
      premarket notification [510(k)] to FDA prior to market. However, even low-risk
      devices may not be acceptable if they are marketed on the basis of misleading or
      excessive claims. Although most color vision devices are diagnostic, two types
      that are therapeutic rather than diagnostic are colored lenses intended to
      improve deficient color vision and colored lenses intended to improve reading
      performance. Both of these devices have presented special regulatory challenges
      to FDA because the intended uses and effectiveness claims initially proposed by
      the manufacturers were not supported by valid scientific evidence. In each
      instance, however, FDA worked with the manufacturer to restrict labeling and
      promotional claims in ways that were consistent with the available device
      performance data and that allowed for the legal marketing of the device.

PMID- 15518231
TI  - Computerized color-vision test based upon postreceptoral channel sensitivities.
AB  - An automated, computerized color-vision test was designed to diagnose congenital
      red-green color-vision defects. The observer viewed a yellow appearing CRT
      screen. The principle was to measure increment thresholds for three different
      chromaticities, the background yellow, a red, and a green chromaticity. Spatial
      and temporal parameters were chosen to favor parvocellular pathway mediation of
      thresholds. Thresholds for the three test stimuli were estimated by four
      alternative forced-choice (4AFC), randomly interleaved staircases. Four 1.5-deg,
      4.2 cd/m2 square pedestals were arranged as a 2 x 2 matrix around the center of
      the display with 15-minute separations. A trial incremented all four squares by
      1.0 cd/m2 for 133 ms. One randomly chosen square included an extra increment of a
      test chromaticity. The observer identified the different appearing square using
      the cursor. Administration time was approximately 5 minutes. Normal trichromats
      showed clear Sloan notch as defined by log (deltaY/deltaR), whereas red-green
      color defectives generally showed little or no Sloan notch, indicating that their
      thresholds were mediated by their luminance system, not by the chromatic system.
      Data from 107 normal trichromats showed a mean Sloan notch of 0.654 (SD = 0.123).
      Among 16 color-vision defectives tested (2 protanopes, 1 protanomal, 6
      deuteranopes, & 7 deuteranomals), the Sloan notch was between -0.062 and 0.353
      for deutans and was < -0.10 for protans. A sufficient number of color-defective
      observers have not yet been tested to determine whether the test can reliably
      discriminate between protans and deutans. Nevertheless, the current data show
      that the test can work as a quick diagnostic procedure (functional trichromatism
      or dichromatism) of red-green color-vision defect.

PMID- 15518232
TI  - Moreland match revisited.
AB  - An earlier analysis, which yielded an optimal pair of blue and green primaries
      (436 & 490 nm) for tritanomaloscopy, is reevaluated. That analysis minimized
      population variance in the mid-match points of color normals by taking into
      account, for a set of blue and green tritanopic metamers, the contributions of
      the lens and macular pigment variances and of matching range. The revision to the
      matching-range contribution takes into account the effect, neglected in the
      original analysis, of the varying angle between the blue-green primary mixture
      lines and the corresponding cyan test and yellow desaturant mixture lines. Use is
      made of new measurements of the macular pigment absorbance spectrum, a new
      estimate of the lens absorbance spectrum, the population variances of the lens
      and macular pigment, and of matching-range data for a current Moreland equation.
      Tritanopic metamers are derived from a revised set of cone fundamentals. The net
      effect of all of these revisions on the specification of optimal primaries is
      small (440 and 488 nm). However, larger changes are involved in the choice of
      test and desaturant wavelengths.

PMID- 15518233
TI  - Modelling the Rayleigh match.
AB  - We use the photopigment template of Baylor et al. (1987) to define the set of
      Rayleigh matches that would be satisfied by a photopigment having a given
      wavelength of peak sensitivity (lambda(max)) and a given optical density (OD).
      For an observer with two photopigments in the region of the Rayleigh primaries,
      the observer's unique match is defined by the intersection of the sets of matches
      that satisfy the individual pigments. The use of a template allows us to
      illustrate the general behavior of Rayleigh matches as the absorption spectra of
      the underlying spectra are altered. In a plot of the Y setting against the red
      green ratio (R), both an increase in lambda(max) and an increase in optical
      density lead to an anticlockwise rotation of the locus of the matches satisfied
      by a given pigment. Since both these factors affect the match, it is not possible
      to reverse the analysis and define uniquely the photopigments corresponding to a
      specific Rayleigh match. However, a way to constrain the set of candidate
      photopigments would be to determine the trajectory of the change of match as the
      effective optical density is altered (by, say, bleaching or field size).

PMID- 15518234
TI  - Quantification of color vision with cone contrast sensitivity.
AB  - Human color vision is based fundamentally on three separate cone photopigments.
      Hereditary color deficiency, which affects up to 10% of males, results from an
      absorption shift or lack of L or M cone phototoreceptors. While hereditary S cone
      deficiency is rare, decreased S cone sensitivity occurs early in eye disease,
      underscoring the importance of quantifying S cone function. Our purpose is to
      describe a novel approach for quantifying human color vision based on the
      photopigments of normal color vision. Colored letters, visible to a single cone
      type, are presented in graded steps of cone contrast to determine the threshold
      for letter recognition. This approach quantifies normal color vision, indicates
      type and severity of hereditary deficiency, and reveals sensitivity decrements in
      various diseases.

PMID- 15518236
TI  - Role of the cripto (EGF-CFC) family in embryogenesis and cancer.

PMID- 15518237
TI  - Wnt signaling: physiology and pathology.
AB  - Signaling by the Wnt family of secreted glycoproteins has been demonstrated to be
      essential both in normal embryonic development and in the pathogenesis of a
      variety of diseases, including cancer. This signaling pathway is exquisitely
      regulated by a large and complex array of proteins, which act as agonists or
      antagonists of signal transduction, modulating the Wnt signal extracellularly, in
      the cytoplasm and in the nucleus. Here, we will briefly review the canonical Wnt
      signaling pathway and consider molecular defects in Wnt signaling components
      known to promote uncontrolled cell growth following induction of Wnt signaling.
      We will also focus on two recently identified factors in this pathway, that seem
      to act as Wnt signaling antagonists, one functioning in the cytoplasm called
      Disabled-2 and the other in the nucleus named Chibby.

PMID- 15518238
TI  - Thrombopoietin signalling in physiology and disease.
AB  - Thrombopoietin (TPO) is a key physiological regulator of steady-state
      megakaryocytopoiesis, the process of megakaryocyte production and maturation that
      ultimately results in the formation of platelets. Ten years have passed since the
      purification and cloning of TPO and extensive studies of the activities of
      recombinant forms of the cytokine, as well as analyses of genetically modified
      mice lacking or over-expressing TPO or its receptor c-Mpl, have defined the role
      of TPO in megakaryocytopoiesis as well as uncovered unanticipated actions.
      Biochemical analyses have identified a number of signalling pathways, including
      the Jak/signal transducers and activators of transcription (STAT) and Ras
      cascades that transmit signals from the activated cell surface receptor complex
      to the cell nucleus resulting in changes in gene expression and the biological
      responses of TPO-stimulated cells. Since TPO is the most potent known stimulus of
      platelet production in vivo, the evaluation of this cytokine for clinical use in
      the treatment of thrombocytopenia is being actively pursued and recent studies
      have suggested that aberrations in the TPO signalling pathway may contribute to
      disease.

PMID- 15518235
TI  - Brain-derived neurotrophic factor.
AB  - Since the purification of BDNF in 1982, a great deal of evidence has mounted for
      its central roles in brain development, physiology, and pathology. Aside from its
      importance in neural development and cell survival, BDNF appears essential to
      molecular mechanisms of synaptic plasticity. Basic activity-related changes in
      the central nervous system are thought to depend on BDNF modification of synaptic
      transmission, especially in the hippocampus and neocortex. Pathologic levels of
      BDNF-dependent synaptic plasticity may contribute to conditions such as epilepsy
      and chronic pain sensitization, whereas application of the trophic properties of
      BDNF may lead to novel therapeutic options in neurodegenerative diseases and
      perhaps even in neuropsychiatric disorders.

PMID- 15518239
TI  - Protective effects of basic fibroblast growth factor in early atherosclerosis.
AB  - OBJECTIVES: The role of basic fibroblast growth factor (bFGF) in atherosclerotic
      plaque formation is incompletely understood. Although it may act as a
      proatherogenic factor due to its stimulatory effect on smooth muscle cell growth,
      previous studies have suggested that it may also have beneficial effects by
      reversing endothelial dysfunction in experimental models. Our purpose was to
      evaluate the effects of systemic chronic administration of basic FGF on the
      development of atherosclerotic plaques in a rabbit model. METHOD: We investigated
      the effect of bFGF or placebo (2.5 microg IV twice a week), begun on the same day
      as a cholesterol (2%) diet, and continued for 5 or 10 weeks, on in vitro
      reactivity, vascular cell adhesion molecule-1 (VCAM-1) expression and plaque
      development (protocol 1; n = 37). The effects of bFGF or placebo (2.5 microg IV
      once a week) were also studied in animals fed a 0.2% cholesterol diet and
      sacrificed at 3 months (protocol 2; n = 18). Results were compared to those of
      rabbits fed with a normal chow (normal animals). RESULTS: In protocol 1, bFGF
      administration for 5 weeks was associated with an improvement in endothelial
      function (p < 0.05), with a decrease in VCAM-1 expression (p = 0.03) and in the
      macrophage content of the plaque (p = 0.02). This preventive effect was lost at
      10 weeks. In protocol 2, bFGF was associated with similar "beneficial" endpoints
      as observed at 5 weeks in protocol 1. CONCLUSIONS: Administration of bFGF is
      associated with important beneficial structural and functional effects in the
      early stage of experimental atherosclerosis. These results may help us to
      understand the role of growth factors in atherosclerosis and to anticipate their
      effects in human arteries.

PMID- 15518240
TI  - Modulation of cathepsin D routing by IGF-II involves IGF-II binding to IGF-II/M6P
      receptor in MCF-7 breast cancer cells.
AB  - The IGF-II/M6P receptor targets cathepsin D to the lysosomes and it also binds
      IGF-II. Although the binding sites for IGF-II and cathepsin D are distinct,
      reciprocal interactions between the ligands have been observed. We have
      demonstrated that proIGF-II expression modulates routing of cathepsin D. To test
      the hypothesis that IGF-II modulation of cathepsin D routing in MCF-7 cells
      involves IGF-II binding to the IGF-II/M6P receptor, we expressed a mutant form of
      IGF-II (Arg54 Arg55) that does not bind the IGF-II/M6P receptor and evaluated its
      effects on cathepsin D secretion. Northern blotting, Western and radioimmunoassay
      analyses confirmed that these cells express high levels of (Arg54 Arg55) IGF-II
      mRNA and secretes high levels of IGF-II without modulating the secretion of
      cathepsin D. These data provide direct evidence that the IGF-II modulation of
      cathepsin D routing is IGF-II/M6P receptor mediated.

PMID- 15518241
TI  - Androgen receptor cross-talk with cell signalling pathways.
AB  - The androgen receptor (AR) is implicated in regulation of cellular events in
      advanced prostate cancer. It is expressed in primary tumours as well as in
      metastases from patients who failed endocrine therapy. Activation of the AR in
      metastatic tumours occurs as a result of increased sensitivity of the receptor,
      point mutations that alter activation spectrum and in response to various
      nonsteroidal compounds. Peptide growth factors that activate the signalling
      pathway of mitogen-activated protein kinases (MAPK) stimulate AR activity in
      ligand-independent or synergistic manner. Outcome of nonsteroidal activation
      depends on cellular and promoter context. AR activation by Her-2/neu is
      associated with enhanced tumour growth of the LAPC-4 xenograft. The issue whether
      MAPK or protein kinase Akt involved in growth factor signalling directly
      phosphorylate the AR is a matter of debate. AR ligand-independent activation by
      protein kinase A activators was also demonstrated. Under physiological
      conditions, potentiation of AR activity by low doses of androgen might be of
      importance in prostate cancer patients who receive endocrine therapy. Interleukin
      6 (IL-6) and related cytokines also activate AR in a ligand-independent and
      synergistic manner. IL-6 is a pleiotropic regulator of tumour growth, which in
      some prostate cancers acts as a paracrine growth inhibitor and in other cases as
      an autocrine growth stimulator. Activation of the AR by IL-6 requires functional
      pathways of Janus kinases/signal transducers and activators of transcription
      factors and MAPK. Studies on AR co-activators implicated in ligand-independent
      activation may further improve understanding of cross-talk between signalling
      pathways.

PMID- 15518242
TI  - Human antibody fragments specific for the epidermal growth factor receptor
      selected from large non-immunised phage display libraries.
AB  - Antibodies to EGFR have been shown to display anti-tumour effects mediated in
      part by inhibition of cellular proliferation and angiogenesis, and by enhancement
      of apoptosis. Humanised antibodies are preferred for clinical use to reduce
      complications with HAMA and HAHA responses frequently seen with murine and
      chimaeric antibodies. We have used depletion and subtractive selection strategies
      on cells expressing the EGFR to sample two large antibody fragment phage display
      libraries for the presence of human antibodies which are specific for the EGFR.
      Four Fab fragments and six scFv fragments were identified, with affinities of up
      to 2.2nM as determined by BIAcore analysis using global fitting of the binding
      curves to obtain the individual rate constants (ka and kd). This overall approach
      offers a generic screening method for the identification of growth factor
      specific antibodies and antibody fragments from large expression libraries and
      has potential for the rapid development of new therapeutic and diagnostic
      reagents.

PMID- 15518243
TI  - Elevated neurotrophin and neurotrophin receptor expression in spontaneously
      hypertensive rat lungs.
AB  - Spontaneously hypertensive rats represent a widely used animal model of
      hypertension. Altered neurotrophin regulation has been related to systemic
      hypertension. Lung cells synthesize and release neurotrophins(NT) which are
      involved in several pulmonary disturbances. Our study explored the expression of
      NT and their receptors using molecular biology and immunohistochemistry.
      Spontaneously 6-, 20- and 29- weeks hypertensive (SHR) and Wistar Kyoto rat (WKY)
      lungs were used. SHR and WKY lungs expressed neurotrophin and neurotrophin
      receptor mRNAs and protein transcripts. Age and hypertension dependent increase
      was clearly noticeable. Furthermore, immunohistochemistry revealed that their
      increase was mainly noticeable within bronchial and vascular components of the
      lung. Although the role of NT in sympathetic hyperinnervation and progression of
      systemic hypertension is a well established phenomenon, their increase in SHR
      lungs, strongly suggest that NT may be operative during pulmonary hypertension
      and in subsequent airway and pulmonary vascular remodeling.

PMID- 15518244
TI  - Fuzzy simulation of pharmacokinetic models: case study of whole body
      physiologically based model of diazepam.
AB  - The aim of the present study is to develop and implement a methodology that
      accounts for parameter variability and uncertainty in the presence of qualitative
      and semi-quantitative information (fuzzy simulations) as well as when some
      parameters are better quantitatively defined than others (fuzzy-probabilistic
      approach). The fuzzy simulations method consists of (i) representing parameter
      uncertainty and variability by fuzzy numbers and (ii) simulating predictions by
      solving the pharmacokinetic model. The fuzzy-probabilistic approach includes an
      additional transformation between fuzzy numbers and probability density
      functions. To illustrate the proposed method a diazepam WBPBPK model was used
      where the information for hepatic intrinsic clearance determined by in vitro-in
      vivo scaling was semi-quantitative. The predicted concentration time profiles
      were compared with those resulting from a Monte Carlo simulation. Fuzzy
      simulations can be used as an alternative to Monte Carlo simulation.

PMID- 15518245
TI  - Visualization-based analysis for a mixed-inhibition binary PBPK model:
      determination of inhibition mechanism.
AB  - A physiologically based pharmacokinetic (PBPK) model incorporating mixed enzyme
      inhibition was used to determine the mechanism of metabolic interactions
      occurring during simultaneous exposures to the organic solvents chloroform and
      trichloroethylene (TCE). Visualization-based sensitivity and identifiability
      analyses of the model were performed to determine the conditions under which four
      inhibitory parameters describing inhibitor binding could be estimated. The
      sensitivity methods were used to reduce the 4-parameter estimation problem into
      two distinct 2-parameter problems. The inhibitory parameters were then estimated
      from multiple closed-chamber gas-uptake experiments using graphical methods. The
      estimated values of the four inhibitory parameters predicted that chloroform and
      TCE interact in a competitive manner. Based on the model analysis, we present
      recommendations for the design of experiments for determination of inhibition
      mechanism in binary chemical mixtures. We assert that a thorough analysis of the
      parameter-dependent sensitivity and identifiability characteristics can be used
      to plan efficient experimental protocols for the quantitative analysis of
      inhalation pharmacokinetics.

PMID- 15518247
TI  - Peritoneal dialysis--a model for partnering with patients in self-management.

PMID- 15518246
TI  - Modeling the short- and long-duration responses to exogenous levodopa and to
      endogenous levodopa production in Parkinson's disease.
AB  - Clinicians recognize levodopa has a short-duration response (measured in hr) and
      a long-duration response (measured in days) in Parkinson's disease. In addition
      there is a diurnal pattern of motor function with better function in the morning.
      Previous pharmacokinetic-pharmacodynamic modeling has quantified only the short
      duration response. We have developed a pharmacokinetic-pharmacodynamic model for
      the short- and long-duration responses to exogenous levodopa and the effects of
      residual endogenous levodopa synthesis in patients with Parkinson's disease.
      Thirteen previously untreated (de novo) patients with Parkinson's disease and
      twelve patients who had received levodopa orally for 9.7+/-4.0 years (chronic)
      were investigated. A 2 hr IV infusion of levodopa with concomitant oral carbidopa
      was given on two occasions separated by 3 days with no levodopa in between. A two
      compartment pharmacokinetic model was used to fit plasma levodopa concentrations.
      A sigmoid Emax model was used to relate concentrations from endogenous and
      exogenous sources to tapping rate (a measure of motor response). A model
      incorporating three effect compartments (fast equilibration (half life, Teqf).
      slow equilibration (Teqs) and dopa synthesis (Teqd)), yielded the most
      descriptive model for levodopa pharmacokinetics and pharmacodynamics. Baseline
      tapping rate reflected endogenous levodopa synthesis and the long-duration
      response. Partial loss of the long-duration response during the 3 days without
      levodopa in the chronic group lowered baseline tapping (36+/-7%, mean+/-SEM) and
      increased maximum levodopa induced response above baseline (112+/-31%). The
      maximum levodopa induced response after the drug holiday is a result of lowered
      baseline tapping due to the loss of long-duration response and not due to a
      change in levodopa pharmacokinetics or pharmacodynamics.

PMID- 15518248
TI  - Commitment & competency & creativity & communication.

PMID- 15518249
TI  - Peritoneal dialysis nursing--we've come a long way.

PMID- 15518250
TI  - How peritoneal dialysis works.
AB  - Successful peritoneal dialysis is based on a patent access, the instillation into
      the peritoneal cavity of a dialysate prescription solution, and an intact,
      functioning peritoneal membrane with adequate blood flow. This article describes
      the basic concepts of peritioneal dialysis.

PMID- 15518251
TI  - Peritoneal dialysis: myths, barriers, and achieving optimum outcomes.
AB  - Peritoneal dialysis provides an excellent alternative to in-center hemodialysis
      but the development of successful programs is often plagued by myths and
      misinformation. A review of recent literature can dispel some of the common myths
      and help understand the barriers to this modality. In addition, achieving optimum
      outcomes in peritoneal dialysis program requires an active continuous quality
      improvement team.

PMID- 15518253
TI  - Interviewing prospective patients for peritoneal dialysis: a five-step approach.
AB  - Interviewing the prospective patient for peritoneal dialysis (PD) is a critical
      step in the development of a relationship between the patient and the PD nurse.
      Individualizing information for the patient and significant others promotes
      confidence in making an informed decision. This article presents a five-step
      approach for interviewing the potential patient for PD.

PMID- 15518252
TI  - Comparison of peritoneal dialysis solutions.
AB  - The composition of peritoneal dialysis solutions to a great extent, determine
      their effectiveness and safety. Many of the factors that determine the
      bioincompatibility of peritoneal dialysis fluids have been recently identified.
      This knowledge is essential to modify the manufacturing processes and in the
      quest for more biocompatible solutions. A description of the available peritoneal
      dialysis fluids in the United States and a comparison of their formulations are
      provided.

PMID- 15518254
TI  - Troubleshooting non-infectious peritoneal dialysis issues.
AB  - Peritoneal dialysis is commonly preformed by patients and their caregivers in the
      home, in nursing homes, and in both acute and rehabilitation hospitals. The
      success of the therapy requires that the nurse overseeing the care of the patient
      on peritoneal dialysis in the acute, sub-acute, and chronic settings has the
      skills and knowledge to identify specific non-infectious issues, choose an
      appropriate and effective intervention activity, document the findings and
      outcomes, and educate the patient to assist in the resolution of the non
      infectious issues, and avoid future recurrence. This article reviews the most
      common non-infectious complications that occur in patients on peritoneal dialysis
      and discusses an organized clinical process to troubleshoot the issues and
      achieve the desired clinical outcomes.

PMID- 15518255
TI  - Use of tissue plasminogen activator in peritoneal dialysis catheters: a
      literature review and one center's experience.
AB  - There have been anecdotal reports of the use of tPA for obstructed peritoneal
      dialysis catheters in both adults and children. This manuscript reviews the
      literature and summarizes common elements of the procedures used for tPA
      administration in peritoneal dialysis catheters. The Gambro New Haven experience
      with administration of tPA (8 mgs in 10 ml of sterile water injected into the
      catheter and allowed to dwell for 1 hour) in 29 cases of catheter obstruction in
      18 patients is presented. Patency was restored in 24 instances with no adverse
      effects. In the 5 cases that did not respond, the primary cause of poor drain was
      catheter malposition in 2, constipation in 2, and adhesions in 1. tPA was also
      administered to 5 patients with relapsing peritonitis; 3 patients, all with
      Staphylococcus epidermidis, recovered and did not experience further recurrence.

PMID- 15518256
TI  - Managing the anemia of end-stage renal disease after hospitalization.
AB  - Aggravation of pre-existing anemia is a common clinical manifestation in patients
      who return to the dialysis facility after being hospitalized. Many of them
      display persistent anemia, with Hb levels remaining below the NKF-K/DOQI minimum
      threshold of 11 g/dL for 6 months or more following hospitalization. Proactive
      management of anemia in the periods before, during, and after hospitalization can
      often minimize the severity of any decrease in Hb while shortening the time
      required to reachieve targeted Hb levels.

PMID- 15518257
TI  - Peritoneal dialysis travel "tool box".
AB  - Patients on peritoneal dialysis (PD) face many challenges when traveling, but
      these challenges can be minimized by pre-travel education, organization, and
      planning. PD nurses play an important role in helping patients on peritoneal
      dialysis understand that travel can continue to be a part of their lives and in
      helping them prepare for, plan, and organize their travel experiences.

PMID- 15518258
TI  - Reflections on "About power in nursing".

PMID- 15518259
TI  - Ensuring best practice in the treatment of peritonitis and exit site infection.
AB  - The outcomes and objectives for KB were met by following a case management tool
      specific to peritonitis and exit site infection. Utilization of the care pathway
      and protocol ensured best practice in the nursing care provided and the medical
      treatment administered. Both the peritonitis and the ESI resolved successfully
      without complications, loss of residual renal function, hospitalization or
      relapse. KB received retraining on technique and prevention and has had no
      further episodes of peritonitis or ESI. She continues to do well on PD and
      maintains her active lifestyle.

PMID- 15518260
TI  - Peritoneal dialysis and hemodialysis: similarities and differences.

PMID- 15518261
TI  - When PD is the only choice... A trusting relationship between nurse and patient
      fosters positive outcomes!

PMID- 15518262
TI  - When PD is the only choice... The patient switching from HD to PD poses a
      clinical and emotional dilemma.

PMID- 15518263
TI  - Strategies to improve albumin in patients on peritoneal dialysis.

PMID- 15518264
TI  - The physician's role in a successful peritoneal dialysis program.

PMID- 15518265
TI  - [An attempt to find major directions in our obstetrics].

PMID- 15518266
TI  - [Intranatal asphyxia, prematurity and congenital infection--their role for brain
      damage in very low birth weight newborns].
AB  - The authors examined 273 newborns weighing less than 1500 g. Their birth weight
      was very low (1001-1500 g) in 179 but extremely low (< 1000 g) in 94 newborns.
      Neurological damage was proved in 101 cases (36.99%). The probable reasons for
      intra- (peri-) ventricular and cerebral hemorrhages in these newborns were the
      following: respiratory distress syndrome (in 11 cases or 10.89%), mother-fetal
      infection (in 16 cases or 15.84%), and combination of asphyxia and infection (in
      10 cases or 9.9%). The severe degree of prematurity (and immaturity) remained the
      only causative factor in the rest 64 premature newborns (63.37% of the cases).
      The results from the distribution of the neurological lesions according to the
      gestational age were also considered. Usage of monofactorial regression models
      detected statistically significant differences between asphyxia, infection and
      brain damage in the newborns of different gestational age.

PMID- 15518267
TI  - [Highlighting some clinical aspects of the association of myoma with pregnancy].
AB  - Leiomyoma is a benign tumor, with mesenchymal embryonal cell origin. During
      pregnancy 0.1 to 4% of cases are diagnosed. MATERIAL, METHODS AND RESULTS: During
      the period of 1999-2003, 59 pregnant and delivering women were registered with
      the diagnosis of Leiomyoma (0.5%) at the ObGyn complex, University Hospital,
      Pleven. In the observed group, were encountered significantly more often primary
      sterility, pathological positions of the fetus and placental pathologies.
      CONCLUSIONS: Leiomyoma frequently complicates the progress of pregnancy and
      delivery necessitating operative intervention by the means of Caesarean Section.

PMID- 15518268
TI  - [Prolactinoma and pregnancy].

PMID- 15518269
TI  - [Torsion of adnexa--complication of quadruplet pregnancy reduction].
AB  - A case of adnexal torsion after quadruplet pregnancy reduction is described.

PMID- 15518270
TI  - [Three years experience of using mycosyst].
AB  - The aim of this study was to estimate therapeutical potentialities of the
      Mycosyst (Fluconazole) preparation, of the Gedeon-Richter company (Budapest,
      Hungary), in women with data for mycotic colpitis. 157 patients for three years
      period (April 2001-2004) were included in this study. Two groups of patients were
      formed. In 104 patients mycotic colpitis was diagnosed during curettage for
      feticide or missed abortion. Another 53 women were treated for mycotic colpitis
      unrelated to pregnancy. Complains of the patients disappear by the 48-th hour and
      in almost all women there were not complaints by the 4-th day. The most quickly
      were influenced itching, discomfort, erythema and dyspareunia and slowly and
      hardly discharge had been influenced. Mycosyst is a broad spectrum antimycotic
      agent of bistriazol type. It has good absorption and tissue saturation. 1-2 hours
      after oral administration maximal plasma concentration is achieved. Plasma half
      life is about 30 hours. This gave us opportunity for single or two doses Mycosyst
      for vaginal candidosis treatment. Use of two doses of 150 mg. was enough for
      acute forms treatment in almost 95% of cases. Mycosyst is sure, easy for use
      broad spectrum antimycotic from the azole group. This preparation is
      comparatively cheep and in the average Bulgarian income possibilities.

PMID- 15518271
TI  - [Bacterial vaginosis in pregnant women--treatment with clindamycin].
AB  - The authors discuss one of the most frequently founded cause of spontaneous
      abortions and prematurity birth--the bacterial vaginosis. The diagnostics is easy
      and not expensive. In the complex of health's caries it is necessary to include
      and the prophylaxis of diagnostics and harmless and efficient treatment with
      local drug as example "Dalacin V".

PMID- 15518272
TI  - [Tot'hema--alternative in the treatment of iron deficiency and iron deficiency
      anemia].

PMID- 15518273
TI  - [Novynette--trends in contraception at the beginning of the new millennium].

PMID- 15518274
TI  - [Administration of activated recombinant factor VII (novo seven) for the control
      of massive bleeding in gynecology].
AB  - We report our clinical opinion for recombinant activated factor VII (NovoSeven,
      Novo Nordisk, Copenhagen, Denmark) administration in gynecology patients with
      massive haemorrhage. 3 women with gynecology deseases and severe bleeding in
      recieved NovoSeven in bolus IV. The blood loss and laboratory changes in
      hematology and haemostasis parameters are monitored. The bleeding was ceased in
      all cases. Decrease in values of Hb, Er and PTT was noted. The use of recombinant
      factor VIIA in gynecology patients with severe bleeding is effective and safe
      enough and could be an alternative to the extreme surgical procedures.

PMID- 15518275
TI  - [Expression of oncogene proteins Bag-1, p53, and bcl-2 in endometrium
      adenocarcinoma with different rate of differentiation].

PMID- 15518276
TI  - [Homocysteine and pregnancy].

PMID- 15518277
TI  - [Intrapartum oxygen saturation in fetus with symptoms of distress shown during
      fetal cardiotocograph monitoring].
AB  - The aim of the study is to establish the mean values of SpO2, during labour with
      symptoms of fetal distress and to find out when fetal hypoxia is expected to
      develop as well as unsatisfactory clinical status of the newborn. The study
      includes 62 women on labour at term with pathological decelerations from the
      fetal heart rate (FHR). SpO2 is monitored by means of fetal pulse oxymeter
      Nellcor N 400. Simultaneously FHR is monitored by means of cardiotocography.
      Fetal well-being is verified by pH u blood gas analysis from fetal scalp while
      the newborn well-being is proven by pH from umbilical artery and Apgar score at
      minute 1 and 5 after birth. The mean continuity of SpO2 recording during the
      first period of labour is 107.84 +/- 25.77 min., with mean 86.74 +/- 7.06%
      reliability of the recordings; for the second period--26 +/- 8.98 min. with
      reliability of the recordings 77.07 +/- 9.96%. During the first period of labour
      the mean value of SpO2 is 43.00 +/- 6.75%. With dilation of 4-5cm SpO2 is 46.25
      +/- 5.92%, with 6-7CM SpO2 is 44.43 +/- 6.39% and with 8-9cm dilation SpO2 is
      42.69 +/- 6.80%. During second period of labour the mean value of SpO2 is 39.14
      +/- 8.41%. There is a statistically significant fall of SpO2 during the second
      period compared to the first period of labour (p<0.05). A correlation exists
      between the values of SpO2 and the well-being of the newborn and a fall of SpO2
      equal or less than 30% is a sign of developing abnormal condition of the newborn.

PMID- 15518278
TI  - [First trimester ultrasound screening for structural and chromosomal anomalies in
      multiple pregnancy].
AB  - AIM OF THE STUDY: To assess the feasibility of first trimester ultrasound
      screening for structural and chromosomal fetal anomalies in multiple gestations.
      METHODS: An observational prospective follow up study was carried out in 32 cases
      of multiple pregnancies. Two scans were scheduled in each case--the first,
      between 6-9 weeks of gestation (w.g.) and the second, between 11-14 w.g. The aim
      was assessment of fetal number, viability, chorionicity/amnionicity and fetal
      biometry. In addition, nuchal translucency [NT] measurement, assessment of risk
      for chromosomal anomalies and fetal anatomy survey were always performed.
      Increased NT > or = 95 percentile and/or detection of structural anomaly were
      considered indications for invasive prenatal diagnosis and fetal karyotyping.
      Selective fetocide was considered in cases of chromosomal or structural anomalies
      and in high-order multiple gestations (> or = 3 fetuses). Pregnancy outcome was
      ascertained by the physical examination of the fetuses, placentas and membranes
      postpartum, the hospital records, the referring physicians or the parents.
      RESULTS: From 32 cases of multiple pregnancies included in the study, 28 were
      twins, and 4--triplets. 68% (19/28) of the twin pregnancies were bichorionic
      biamniotic [Bi-Bi], 25% (7/28)--monochorionic-biamniotic [Mo-Bi] and 7% (2/28)-
      monochorionic-monoamniotic [Mo-Mo]. 4 cases of increased NT in one of the twins
      (1--associated with trisomy 21) were observed, as well as 2 cases of structural
      fetal anomalies (1--discordant for exencephaly, and 1--with conjoint twins), 2
      cases of feto-fetal transfusion syndrome that developed in the second trimester
      (1--associated with increased NT between 11-14 w.g.), 1 case of TRAP syndrome
      [twin-reversed arterial perfusion] and 1 case of cord entanglement in
      monoamniotic twins. In addition, there were 4 cases of a vanishing twin in the
      first trimester, and in 2 other cases spontaneous miscarriage of both twins
      occurred before 24 w.g. In two of the triplet pregnancies selective fetocide was
      performed, one was successfully delivered at 33 w.g. and in the last case the
      parents chose to terminate the pregnancy. CONCLUSIONS: First trimester ultrasound
      is a method of choice for detection of major structural fetal anomalies in
      multiple gestations. Increased NT between 11-14 w.g. in multiple pregnancies is a
      useful screening tool for detection of chromosomal fetal anomalies, while in
      monochorionic twins its presence might predict the development of fetofetal
      transfusion syndrome. First trimester selective fetocide in high-order multiple
      gestations or in affected twins is one of the options in pregnancy management.

PMID- 15518279
TI  - [Diagnostic value of the Doppler ultrasound of kidney vessels in pregnancy
      complicated with preeclampsia].
AB  - Preeclampsia (PE) is a complication of the second half of the pregnancy whose
      clinical course is hypertension and proteinuria with or without edema. Its
      pathogenesis is characterized with generalized vasoconstriction and endothelial
      dysfunction. The aim of this study is to evaluate the diagnostic value of the
      Doppler ultrasound examination of the renal interlobar vessels in pregnancy
      complicated with preeclampsia in the context of the theory of the increased
      vessel resistance in this pregnancy disorder.

PMID- 15518280
TI  - [Utrogestan and high risk pregnancy].
AB  - Utrogestan is a modern progesterone, which shows maximal effectiveness with
      minimal side effects. It is a natural progesterone in micronized form, which
      makes it suitable for oral administration and vaginal application with same
      effectiveness. The aim of our retrospective study was to evaluate the
      therapeutical effects of Utrogestan in women with threatened abortion in the
      first trimester. Our experience dated from about one year and a half. Sixty eight
      women were treated for threatened abortion with a daily dose of 400 mg
      Utrogestan. The treatment continued at least 14 days/average 21 days/. Utrogestan
      was administered orally twice daily. The main indications were first or
      consecutive threatened spontaneous abortion in first trimester. For the period of
      time no side effects and subjective complaints were established except particular
      cases of slight headache and dizziness after morning application. Sixty one of
      the sixty eight women were dehospitalised with healthy pregnancy with no side
      effects. In our experience we preferred to use the drug in women with lutein
      insufficiency before pregnancy. We conclude that Utrogestan can be widely applied
      in Obstetrics with the proper indications, such as threatened abortion in the
      first trimester. The prophylactic treatment in women with slighter complaints
      like dull pain and weight Utrogestan is applied one tablet twice daily. In graver
      cases the starting dosage is two tablets two or three times daily.

PMID- 15518281
TI  - [The significance of parameters of the acid-base status, blood gas and blood
      lactate level for the adequate resuscitation and prognosis in newborns with very
      low birth weight].
AB  - The aim of this prospective study was to optimize the resuscitation guidelines
      for VLBW and ELBW premature newborns, to improve their life prognosis and to
      minimize the permanent complications of the perinatal asphyxia. RESULTS: The
      newborns were divided in 2 groups: main group--28 ELBW and 55 VLBW infants born
      from 01.10.01 to 30.06.02; and control group--52 ELBW and 78 VLBW infants, born
      in year 2000 in "Maichin dom". More intensive resuscitation was given to the VLBW
      newborns in the mean group--58% of them were intubated and ventilated in Delivery
      room (DR) infants compared with 40% from the controls. In the ELBW groups the
      rate of the assisted ventilation (AV) remains high (85% and 82%) but more often
      we insufflated Surfactant for prophylaxis of the RDS (71% compared with 52% in
      the controls). This, as well as the precisely monitoring of the early postnatal
      adaptation--pulsoxymetry, parameters of acid-base status (ABS) and homeostasis,
      resulted in significantly reduction of the mortality rate in ELBW infants from
      46% to 18%. We found a reduction of the severe neurological injuries and high
      degree retinopathy of prematurity too. We evaluated the lactate values and the
      ABS parameters in blood from umbilical artery (u.a.) and from arterial blood 1
      hour after birth. We found out that the low lactate levels in u.a. didn't
      correlate with the degree of the metabolic acidosis (pH and BE). Correlation
      between high lactate levels in u.a, low pH and BE were found predominantly in
      newborns with significant intrauterine retardation and chronic placental
      insufficiency. Levels > 5.0 mmol/l 1h after birth and the persistence of the
      metabolic acidosis despite an adequate resuscitation determinated in principle
      bad outcome and severe complications. CONCLUSIONS: The adequate DR resuscitation
      under strict monitoring of the cardio-pulmonary adaptation and the prophylactic
      Surfactant application improve the survival rate and the prognosis of the ELBW
      newborns. The persistence of high lactate levels in combination with a metabolic
      acidosis and intrauterine retardation are bad prognostic criteria for outcome.

PMID- 15518282
TI  - [Active screening for genetic pathology in newborns. II. Genetic counseling and
      prenatal diagnosis in high risk families].
AB  - Active screening for genetic pathology over a period of 12 years (1990-2001)
      involved examination of 29629 newborns at the Clinic of Obstetrics and
      Gynaecology. Congenital anomalies were detected in 1244 cases (live-, stillbirths
      and terminated pregnancies) which gives an average incidence rate of 42.0 per
      1000 among the studied population. Chromosomal abnormalities were diagnosed in 70
      cases (5.6%), single gene conditions--in 164 cases (13.2%), multifactorially
      determined conditions--in 449 cases (36.1%). The total genetic contribution of
      all recognized cases with genetic conditions was 54.9% (683 cases). Genetic
      counseling was provided to 560 out of 1244 (45%) couples who given births to
      affected children. During that period prenatal diagnosis was performed on 110
      (44%) pregnancies and most of them (90%) ended successfully (healthy child was
      born). Our strategy for identifying CD by active screening enabled us to provide
      more accurate genetic counselling and prenatal diagnosis for genetic diseases.
      Screening of newborn population is likely to be an effective and necessary
      service.

PMID- 15518283
TI  - [Results of cytoreductive surgery for advanced and recurrent ovarian neoplasms
      and papillary serous carcinomas of the peritoneum].
AB  - The aim of our study was to review and show the long-term results of the
      cytoreductive surgery in the treatment of advanced primary and recurrent
      epithelial ovarian cancers and papillary serous carcinomas of the peritoneum. We
      wanted to find clinical factors and in this way to select patients who can
      benefit from this kind of treatment. The clinical data of 32 patients searched
      retrospectively are presented in our research work. In 29 patients was possible
      radical cytoreductive surgery. Neoadjuvant and early postoperative chemotherapy
      were applied in most of the patients. The median follow up after cytoreductive
      surgery was 50 months. The overall median survival after cytoreduction was 38.5
      months. We consider the cytoreductive surgery to be effective only when combined
      with neoadjuvant or with early postoperative chemotherapy. The surgical approach
      without chemotherapy leads to bad results.

PMID- 15518284
TI  - [Measurement of basal inhibin B level in Bulgarian women of the childbearing
      age].
AB  - OBJECTIVE: To establish mean and reference range of basal serum inhibin B levels
      in a group of healthy fertile Bulgarian women. METHODS: The present report covers
      the results of 9 month's period in which sixty-five healthy fertile Bulgarian
      women, aged 20-40 years were selected to determinate a reference group of healthy
      fertile women with normal values of inhibin B. Blood samples were collected on
      early follicular phase of menstrual cycle (2-4 days). Inhibin B was analyzed in
      duplicate with the use of a double-antibody ELISA. RESULTS: We established mean
      values of inhibin B 121.22 (+/- 45.04) pg/ml in a group of 65 healthy fertile
      Bulgarian women with mean 30.78 (+/- 3.94) years of age. The values of inhibin-B,
      which we obtained in the 5th percentile, was 33.15 pg/ml and in the 95th
      percentile was 190.75 pg/ml. CONCLUSIONS: The measurement of inhibin B is a test
      easy for performance, with reference values for healthy fertile Bulgarian women
      between 33.15 pg/ml and 190.75 pg/ml.

PMID- 15518285
TI  - [Recombinant factor VII-a--new possibility for the treatment of severe postpartal
      bleeding--literature review].

PMID- 15518286
TI  - [Sucessful pregnancy outcome following three severe placental abruptions and
      intrauterine fetal death in the patient--heterozygous carrier of R506Q mutation
      of factor V (Leiden)].
AB  - A case of successful pregnancy outcome is reported in a patient with 3 preceding
      severe placental abruptions with intrauterine fetal death and caesarean
      deliveries. In the course of the current pregnancy heterozygosity for R506Q
      mutation of factor V (Leiden) was diagnosed in 26 weeks of gestation [w.g.] and
      low molecular weight heparin [LMWH] therapy initiated. Maternal condition was
      stable until delivery and all laboratory findings were within normal range. The
      fetus was followed up by ultrasound biometry and Doppler blood flow studies. From
      28 w.g. on NST and biophysical profile were included. An emergency caesarean
      section was performed in 34 w.g. because of contractions not responding to
      tocolysis. The newborn was in good condition with weight and length corresponding
      to the 10th centile for gestational age [g.a]. Histologic study of the placenta
      showed anemic infarctions and recent haemorrhages in the basal and the chorionic
      plate. The initiation of LMWH therapy in the case reported was late (26 w.g.). By
      that moment there was already evidence of impaired fetal growth with fetal
      biometry corresponding to the 10th centile for g.a. After LMWH therapy was
      started no further slow down of fetal growth was registered. Successful pregnancy
      outcome may be related not only to LMWH therapy but also to other factors like
      active fetal monitoring after 28 w.g. and the emergency caesarian delivery
      immediately after the onset of uterine contractions. Patients with past obstetric
      history of severe preeclampsia, placental abruption or fetal growth restriction
      have to be screened for hereditary or acquired thrombophilia. If a thrombophillic
      state is present early LMWH therapy has to be considered. It is aimed to prevent
      anaemic placental infarctions and thrombotic complications.

PMID- 15518287
TI  - ["For" and "against" the use of cytotec in obstetrics and gynaecology].
AB  - The aim of this outlook was to study the application of Misoprostol in obstetrics
      and gynaecology. Because this preparation is not approved for use in Bulgaria,
      publications on the topic from various journals cited in Medline, Cochrane
      library, Nature, Science, Lancet, GyneWeb and others have been taken into
      consideration. Indications, methods of administration, dosages and side effects
      in use of this drug were described.

PMID- 15518288
TI  - [Iron-deficiency anaemia in everyday gynaecological practice].
AB  - INTRODUCTION: Iron-deficiency anaemia /IDA/ is of utmost significance to clinical
      practice. Chronic haemorrhages from the genital tract are the major etiological
      factor for its appearance in 60-70% of the patients. Abnormal genital bleeding
      for the specialist in Obstetrics and gynaecology and IDA for the haematologist
      are frequently met problems in their everyday practice, which require detailed
      examination, good colaboration and synchronization between the work of both
      specialists. PURPOSE: Diagnosing and etiological treatment of IDA of gynaecologic
      origin by mutual timely and adequate co-operation of gynaecologist and
      haematologist. MATERIALS AND METHODS: Clinical survey based on the algorithm
      worked out. Its everyday application started in July-August 2001 and till today
      /30.04.2003/ 253 cases with IDA in the Department of Gynaecology are taken in. A
      record of proceedings was made for every patient and that helped the further
      diagnostic and therapeutic activity and respective data processing. RESULTS AND
      DISCUSSION: The data and results obtained verify the achievement of final
      diagnostic specification of IDA, the role of the algorithm as a stepping-stone to
      its etiological treatment, complete and durable correction of iron deficiency.

PMID- 15518289
TI  - A catalogue of selected derivatization reactions to label molecules in the
      subnanomolar or nanomolar range for CE and micro-HPLC with LIF detection.
AB  - Sensitivity is a major obstacle to biochemists studying complex biological
      mixtures. Laser-induced fluorescence (LIF) is a very sensitive method that can be
      used with micro-HPLC (microHPLC) or capillary electrophoresis studies and
      provides an effective solution to these problems. Derivatization is a very useful
      tool in LIF detection because it allows for the detection of many compounds and
      is selective, i.e., one dye will label one chemical function specifically. The
      major difficulty is choosing a derivatization reaction among the huge number of
      reactions described in the literature and making it work at a very low level of
      concentration. Another limitation is the use of a laser wavelength, which can
      excite the derivatized molecules. This article discusses selected derivatization
      reactions for labeling molecules in the subnanomolar or nanomolar range for CE
      and microHPLC. Derivatization for amines, sugars, aldehydes, carboxylic acids,
      thiols, diols, and nucleotides are described, and derivatization procedures are
      presented. In many cases, the subnanomolar and nanomolar concentration of these
      compounds can be detected using these chemical reactions.

PMID- 15518290
TI  - Optimization of enantiomeric separations in capillary electrophoresis by applying
      a design of experiments approach.
AB  - During early-phase pharmaceutical development, it is important to find an initial
      separation of enantiomeric compounds quickly in order to determine the
      enantiomeric purity of chiral drug substances. Highly selective screening methods
      are necessary to analyze the products to discover a satisfactory separation of
      the enantiomeric compounds. A screening approach based on the use of mixtures of
      multiple cyclodextrins in chiral capillary electrophoresis was employed to find
      the initial separation of chiral compounds. In a later phase of development,
      these complex methods need to be simplified for transferability. This study
      describes the simplification of the complex mixture of cyclodextrins into a
      single or dual system of only the enantioselective cyclodextrins. This was
      achieved by applying fractional factorial experimental designs to select the
      cyclodextrins that were responsible for the enantiomeric separation and response
      surface modeling designs for the optimization of the separation. In order to
      obtain robust methods, the concentration of the chiral selector, together with
      other important electrophoretic method parameters such as the concentration of
      the background electrolyte, pH, and run voltage, were optimized by employing a
      Box-Behnken experimental design.

PMID- 15518291
TI  - Capillary electrophoresis of cereal proteins: an overview.
AB  - Cereal grains are important both nutritionally and economically in virtually
      every country in the world. Cereal grains can be made into a wide range of human
      foods and are also important animal feed components. Although all of the
      biochemical components of cereal grains are important, cereal proteins play major
      functional, as well as nutritional, roles in foods. Cereal proteins are complex
      mixtures of proteins that are often difficult to solubilize and separate. Because
      of this, a wide range of analytical techniques have been used to separate and
      characterize cereal proteins. One of the new techniques used to separate these
      challenging proteins is high-performance capillary electrophoresis (HPCE). This
      review covers methods developed to separate cereal proteins by HPCE.

PMID- 15518292
TI  - Sports medicine, sports science: the multidisciplinary road to sports success.

PMID- 15518293
TI  - Player movement patterns and game activities in the Australian Football League.
AB  - In the Australian Football League (AFL), specific game movements and activities
      have not been studied since the 1970s and 1980s and the game is now much faster
      than it was 20-30 years ago. Using lapsed-time video analysis, AFL players from
      five different positions (full forward/full back, centre half forward/centre half
      back, small forward/small back, mid fielders and ruckmen) had their movement
      patterns (stand, walk, jog, fast-run, sprint, change of direction) and game
      activities (possessions, ruck duels, ground ball contests, shepherds, spoils,
      bumps and tackles) recorded in two games each in the 2000 season. A descriptive
      analysis of the results was undertaken. The main findings were: full forward/full
      back were most different from the other positions, as they were seen to stand
      more and jog and fast-run less: ruckmen and midfielders were involved in more
      game activities than the other positions; for all positions, there were more than
      150 high intensity movements (fast-run plus sprint) in the game, but these
      accounted for only 4-6% of total movement time: virtually all of the high
      intensity movements lasted for <6 secs; more than half of all sprints involved at
      least one change of direction, mostly within the 0-90 degrees arc (left or right)
      and all ground ball contests took <6 secs, with midfielders having 2-3 times as
      many as the other positions. Improvements in specific pre-season and in-season
      training practices for different positions should be possible after careful
      interpretation of these findings.

PMID- 15518294
TI  - Comparison of training activities and game demands in the Australian Football
      League.
AB  - his paper serves as a companion to our recent study of the movement patterns and
      game activities of players (from five different positions) during matches in the
      2000 Australian Football League season. Using lapsed-time video analysis, the
      same individual players (n= 11) as filmed in matches were also monitored during
      21 in-season, main training sessions conducted by their clubs in order to assess
      the degree to which training activities matched game demands. In general, the
      training sessions did not involve physical pressure; therefore there were very
      few contested marks and ground balls or tackles, shepherds and spoils, thereby
      not matching these game demands. Players typically had more possessions (kicks
      and handballs) at training than in games. They also spent a greater percentage of
      total time standing and less time walking at training than in games. Fast-running
      and sprinting efforts at training were almost all for durations of <6 secs, which
      matched game demands, as did changes of direction when sprinting, which were
      almost all in a 0-90 degrees arc. However, across all players filmed, high
      intensity (fast-running and sprinting) movements were not performed as frequently
      at training (one every 76 secs) as in games (one every 51 secs). Therefore, while
      some game demands were adequately replicated at training, others were not closely
      simulated, suggesting that, after careful interpretation of these results, some
      improvements in training practices could be made.

PMID- 15518295
TI  - Energy system contribution to 100-m and 200-m track running events.
AB  - While sprint track running events, lasting 10-25 secs, are characterised by an
      anaerobic metabolic dominance, no actual track running data exist which have
      quantified the relative energy system contributions. Using previous methods
      employed by our laboratory, including 'in race' measures of VO2, accumulated
      oxygen deficit (AOD), blood lactate concentration and estimated phosphocreatine
      degradation (La/PCr), the aerobic-anaerobic energy system contributions to 100-m
      and 200-m events were calculated. For the 100-m event, results indicated a
      relative aerobic-anaerobic energy system contribution (based on AOD measures) of
      21%-79% and 25-75% for males and females respectively (9%-91% and 11%-89% based
      on La/PCr measures; p<0.05 for both genders for 100-m from AOD estimates). For
      the 200-m, a 28%-72% and 33%-67% contribution for male and female athletes was
      estimated (21%-79% and 22%-78% based on La/PCr measures; NS from AOD estimates).
      A range of energy system contribution estimates for events of these durations
      have previously been proposed using a variety of techniques. The data from the
      current study also show different results depending on the measurement technique
      utilised. While AOD measures are often used to estimate anaerobic energy
      contribution, at such high exercise intensities (and brief exercise durations) as
      used in the present study, AOD measures showed larger aerobic energy estimates
      than expected.

PMID- 15518296
TI  - Muscle metabolism during sprint exercise in man: influence of sprint training.
AB  - In order to examine the influence of sprint training on metabolism and exercise
      performance during sprint exercise, 16 recreationally-active, untrained, men
      (VO2peak= 3.8+/-0.1 l.min(-1)) were randomly assigned to either a training (n= 8)
      or control group (n= 8). Each subject performed a 30-sec cycle sprint and a test
      to measure VO2peak before and after eight weeks of sprint training. The training
      group completed a series of sprints three times per week which progressed from
      three 30-sec cycle sprints in weeks 1 and 2, to six 30-sec sprints in weeks 7 and
      8. Three mins of passive recovery separated each sprint throughout the training
      period. Muscle samples were obtained at rest and immediately following the pre-
      and post-training sprints and analysed for high energy phosphagens, glycogen and
      lactate; the activities of both phosphofructokinase (PFK) and citrate synthase
      (CS) were also measured and muscle fibre types were quantified. Training resulted
      in a 7.1% increase in mean power output (p<0.05), an 8% increase in VO2peak (p<
      0.001), a 42% increase (p< 0.01) in CS activity and a 17% increase (p< 0.05) in
      resting intramuscular glycogen content. In contrast, neither PFK activity nor
      fibre type distribution changed with training. An increase (p< 0.05) in mean
      power output and attenuated (p< 0.01) ATP degradation were observed during sprint
      exercise following training. Glycogen degradation during sprint exercise was
      unaffected by sprint training. These data demonstrate that sprint training may
      have enhanced muscle oxidative but not glycolytic capacity.

PMID- 15518297
TI  - Longitudinal assessment of the effects of field-hockey training on repeated
      sprint ability.
AB  - Repeated-sprint ability is thought to be an important fitness component of team
      sports. However, little is known about the effect sport-specific training has on
      this fitness component. Therefore, the purpose of this study was to investigate
      the effects of field-hockey specific training on repeated-sprint ability, plasma
      hypoxanthine (Hx) concentration and other blood parameters in 18 elite female
      field-hockey players. All subjects performed a repeated-sprint ability test on a
      cycle ergometer (5 x 6-sec maximal sprints every 30 secs) before and after seven
      weeks of training, designed to improve repeated-sprint ability. Following
      training, there was a significant (P< 0.05) increase in absolute total work
      (20.73+/-2.00 to 21.15+/-2.07 kJ, mean+/-SD). However, there was no significant
      change in total work when expressed per kg of body mass (341.3+/-16.4 to 345.5+/
      18.8 J x kg(-1)). In addition, training resulted in a significant (P< 0.05)
      decrease in change values (peak-rest values) for Hx (8.2+/-3.8 to 5.5+/-2.7
      micromol x L(-1)) and hydrogen ion concentration (22.8+/-5.2 to 19.1+/-5.1 nmol x
      L(-1)). The significant increase in absolute total work following seven weeks of
      field-hockey specific training was most likely due to an increase in lean muscle
      mass. The significant decrease in plasma Hx concentration (post-test minus rest
      values) following seven weeks of field hockey-specific training provides evidence
      that Hx production and/or efflux from the muscle are reduced. Therefore, one
      adaptation of sport-specific repeated-sprint training may be to conserve the
      purine nucleotide pool.

PMID- 15518298
TI  - Changes in stress and recovery after heavy training in rowers.
AB  - In this study, the effect of rapidly increased training volume on performance,
      recovery-stress state and stress hormones over a six-day training camp were
      investigated in competitive male rowers (n=21). The training regimen consisted
      mainly of low-intensity on-water rowing and resistance training, in total 19.6+/
      3.8 hrs, corresponding to approximately 100% increase in training load. Two
      thousand metre rowing ergometer performance time worsened by the end of a heavy
      training period. The resting blood testosterone decreased and cortisol remained
      unchanged. The Recovery-Stress-Questionnaire for Athletes (RESTQ-Sport) revealed
      an increase in somatic components of stress (Fatigue, Somatic Complaints,
      Fitness/Injury) and a decrease in recovery factors (Success, Social Relaxation,
      Sleep Quality, Being in Shape, Self-Efficacy). Relationships were observed
      between training volume, and Fatigue (r=0.49), Somatic Complaints (r=0.50) and
      Sleep Quality (r=-0.58) at the end of heavy training. In addition, relationships
      were also observed between cortisol and Fatigue (r=0.48) at the end of heavy
      training as well as between changes in cortisol and changes in Fatigue (r=0.57)
      and Social Stress (r=0.51). In conclusion, changes in specific stress and
      recovery scales of the RESTQ-Sport for athletes and changes in stress hormone
      values indicated a state of heavy training stress and incomplete recovery at the
      end of a six-day heavy training period.

PMID- 15518299
TI  - Influence of injuries on team playing performance in Rugby League.
AB  - All injuries have the potential to impact on individual sporting performance and
      as a result may influence team playing performance. However, the influence of
      injuries on team playing performance is unclear. The purpose of this study was to
      investigate the influence of injuries on team playing performance in Rugby
      League. All injuries sustained by one semi-professional first grade Rugby League
      team were prospectively studied during the 2001 competitive season. An injury was
      defined as any pain or disability suffered by a player during a match. Team
      playing performance for each match was estimated from the metres gained while in
      possession of the football, points scored, points conceded, the final points
      differential and the completion rates of attacking sets of tackles. A total of
      294 injuries were recorded. The average metres gained for all matches was 1471
      (95% confidence interval, CI: 1383 to 1559) m. The team averaged 42 (95% CI: 32
      to 51) points in attack each match and conceded an average of 15 (95% CI: 9 to
      21) points in defence. The average completion rate for the season was 65.3 (95%
      CI: 60.6 to 70.0)%. There was no significant association (p>0.05) between the
      number of injuries sustained and team-playing performance. These findings suggest
      that injuries have minimal impact on team-playing performance in Rugby League.
      Further research on a larger sample (including winning and losing teams), is
      required to provide a detailed analysis of the influence of injuries on team
      playing performance in Rugby League.

PMID- 15518300
TI  - Reviewing knee osteoarthritis--a biomechanical perspective.
AB  - Osteoarthritis (OA) is the most common form of arthritis and is a major cause of
      disability in people aged over 65. Despite the major socioeconomic burden imposed
      by OA, the aetiology of this condition remains unclear. Although controversial,
      several metabolic factors have been implicated in the disease pathogenesis.
      Nevertheless, no unequivocal systemic risk factors for the onset or progression
      of OA have been identified. Recently, there has been a growing interest in the
      biomechanical factors associated with the pathogenesis of OA. This review aims to
      discuss several of the more pertinent biomechanical and neuromuscular factors,
      such as the knee adduction moment and muscle strength, that are becoming
      increasingly accepted as factors that contribute toward the pathogenesis of knee
      OA.

PMID- 15518301
TI  - Mastery of fundamental movement skills among children in New South Wales:
      prevalence and sociodemographic distribution.
AB  - Fundamental movement skills form the foundation for many of the specific motor
      skills employed in popular sports and leisure activities. Little data exist on
      the prevalence and socioeconomic distribution of fundamental movement skill
      mastery among young children in Australia. This study process-assessed
      performance on six fundamental movement skills in a randomly selected sample of
      students from Years 1 through 3 in the Sydney metropolitan area of New South
      Wales. The prevalence and sociodemographic distribution of mastery and near
      mastery for each skill and each skill component is reported for boys and girls in
      each school year. The findings revealed that the prevalence of mastery and near
      mastery of each of fundamental movement skill was generally low. Boys performed
      significantly better than girls in the run and in the four object-control skills
      (throw, catch, kick, and strike) whilst girls performed better than boys in the
      skip. There was no consistent association between prevalence of skill mastery and
      socio-economic status (SES), with only the kick and vertical jump for boys and
      catch, dodge, and vertical jump for girls differing across SES tertiles. Based on
      these results, we recommend that adequate curriculum time, resources, and
      professional development continue to be devoted to fundamental movement skills in
      NSW primary schools.

PMID- 15518302
TI  - Musculoskeletal health in elite male adolescent middle-distance runners.
AB  - The impact of high training volumes on musculoskeletal adaptations of male
      adolescents is poorly understood. We compared bone mineral content (BMC) of total
      body, lumbar spine and proximal femur using Dual X-ray Absorptiometry (Lunar
      Prodigy, GE Medical Systems, Madison WI) in elite level (n=20), male adolescent
      middle distance runners (mean 16.8 yrs, range 14-18 yrs) and age-matched (n=20)
      controls. Athletes averaged 14 hrs of physical activity per week and controls
      reported participating in physical activity an average of two hrs per week. Total
      body mass was 10.97 kg less in athletes than controls (p=0.005). Within the total
      body mass difference, fat tissue mass of athletes was 10.93 kg less in athletes
      than controls (p= 0.001). Multiple regression analysis identified total body lean
      mass and total body fat mass as the strongest predictors of total body BMC (R2
      0.71). After adjusting for lean tissue mass per kg of body weight (p=0.07), no
      difference in BMC was detected. Lower limb muscle strength and macronutrient
      intakes were also measured but no between group differences were found. The
      number of weeks of training and/or competition missed through injury was not
      associated with total body BMC (R2=0.19) among athletes. Our results imply high
      training volumes in middle distance running are not detrimental to
      musculoskeletal health and are associated with positive body composition profiles
      in elite adolescent male athletes.

PMID- 15518303
TI  - Incidence and risk factors for injury in non-elite Australian Football.
AB  - This paper identifies the risk and protective factors for injury in non-elite
      Australian Football. Five hundred and thirty five non-elite Australian
      footballers completed a baseline questionnaire at the commencement of the 1997
      preseason. Participants were telephoned each month during the 1997 and 1998
      playing seasons to provide details of their exposure at training and games and
      any injury experiences in the previous four weeks. The incidence of injury in
      this study was 24 injuries per 1000 player hours. The risk factors for injury
      were identified as: not wearing sports-specific football boots (IRR 1.40, 95% CI
      1.03-1.90); an existing back pathology (IRR 1.29, 95% CI 1.10-1.51); excessive
      foot pronation (IRR 1.29, 95% CI 1.07-1.56); and extroverted behaviour (IRR 1.01,
      95% CI 1.00-1.03). Cooling down after training (IRR 0.95, 95% CI 0.90-0.99) and
      not being injured in the previous 12 months (IRR 0.73, 95% CI 0.61-0.88) were
      found to be protective against injury. This study found that there was a high
      risk of injury associated with playing Australian Football at a community level.
      Further research is required to gain an understanding of the mechanisms by which
      the identified risk factors influence injury risk in community level Australian
      Football.

PMID- 15518304
TI  - Anatomical variations within the deep posterior compartment of the leg and
      important clinical consequences.
AB  - The management of musculoskeletal conditions makes up a large part of a sports
      medicine practitioner's practice. A thorough knowledge of anatomy is an essential
      component of the armament necessary to decipher the large number of potential
      conditions that may confront these practitioners. To cloud the issue further,
      anatomical variations may be present, such as supernumerary muscles, thickened
      fascial bands or variant courses of nerves and blood vessels, which can
      themselves manifest as acute or chronic conditions that lead to significant
      morbidity or limitation of activity. There are a number of contentious areas
      within the literature surrounding the anatomy of the leg, particularly involving
      the deep posterior compartment. Conditions such as chronic exertional compartment
      syndrome, tibial periostitis (shin splints), peripheral nerve entrapment and
      tarsal tunnel syndrome may all be affected by subtle anatomical variations. This
      paper primarily focuses on the deep posterior compartment of the leg and uses the
      gross dissection of cadaveric specimens to describe definitively the anatomy of
      the deep posterior compartment. Variant fascial attachments of flexor digitorum
      longus are documented and potential clinical sequelae such as chronic exertional
      compartment syndrome and tarsal tunnel syndrome are discussed.

PMID- 15518305
TI  - Presentation and mechanisms of concussion in professional Rugby League Football.
AB  - The present study prospectively recorded the circumstances, incidence,
      mechanisms, injury detection and presentation of concussion in Rugby League.
      Forty-three consecutive concussions were recorded over three competitive seasons
      in 175 professional Rugby League players. Data showed (i) the incidence of
      concussion ranged from 5.9 to 9.8 injuries/1000 player hours across grades -
      except when age-group players were mismatched (18.4): (ii) 'head-high tackles'
      accounted for a significant number of concussions; (iii) concussion rarely
      involved a loss of consciousness with the most common indicators of concussion
      being amnesia, headache and unsteadiness, with the mechanism of injury often
      missed: and (iv) concussion often occurs concurrently with other injuries.
      Concussion (including repeated episodes) is a common injury in Rugby League.
      Systematic mental status questioning is warranted whenever concussion is
      suspected. Coaches, trainers and players need more education in the recognition
      and management of concussion. Stricter penalties for illegal 'head-high' tackling
      are strongly recommended.

PMID- 15518306
TI  - Endorsement of physical activity recommendations for children and youth in
      Australia.

PMID- 15518307
TI  - [Social phobia in children and adolescents].
AB  - Epidemiological data indicate that anxiety disorders are the most common
      childhood disorders. 1% of children and adolescents suffer from social phobia and
      it may influence further adult life. The aim of the article is to show
      differences of child and adolescent social phobia and its diagnostic criteria.
      Contrast and distinction of childhood social phobia symptoms are also shown, such
      as risk factors of appearance of childhood social phobia. The article presents
      main therapeutic methods--psychotherapy and pharmacotherapy applied to children
      with phobia and difficulties with estimating efficacy of the particular therapy
      in this group of patients. Phobic children perceive surroundings more negatively.
      They have reduced estimations of their own competency to cope with danger. They
      also show cognitive impairments of ambiguous situations. As much as 60% children
      with social phobia suffer from a second, concurrent disorder. Widening of
      information about symptoms and therapeutic methods may reduce the intensity of
      the disorder during adulthood.

PMID- 15518308
TI  - [Comorbidity of different forms of anxiety disorders and depression].
AB  - AIM: Comorbidity of some anxiety disorders and depression were examined in order
      to compare their statistical closeness. METHOD: Patients treated in an out
      patient care center for psychiatric disorders and/or family medicine were
      recruited. Persons that have anxiety and depressive symptoms as a consequence of
      somatic illnesses or consequence of other psychiatric disorders were excluded.
      Disorders were diagnosed a with diagnostic questionnaire based on Schedule for
      Assessment in Neuropsychiatry (SCAN), version 2.0, according to ICD-10 criteria.
      Analyses include selected disorders: generalized anxiety disorder, panic
      disorder, agoraphobia, specific phobias, social phobia and depression. RESULTS:
      104 patients were included. 35 of them (33.7%) had anxiety disorders, 13 persons
      (12.5%) have depression. Analyses show that in patients with generalized anxiety
      disorder, depression occurred at least twice as often as in the remaining
      patients (odds ratio = 7.1), while in patients with agoraphobia the occurrence of
      panic disorder increased at least by 2.88 times (odds ratio = 11.9). In other
      disorders the odds ratios was greater than 1, but the differences were not
      statistically significant. CONCLUSION: Depression/generalized anxiety disorder
      and agoraphobia/panic disorder were shown to be statistically closer than other
      disorders.

PMID- 15518309
TI  - [Effects of exercise on anxiety, depression and mood].
AB  - This article reviews the studies on the effects of physical activity on the
      emotional states--anxiety, depression and mood. The meta-analyses of
      correlational and experimental studies reveal positive effects of exercise, in
      healthy people and in clinical populations (also in patients with emotional
      disorders) regardless of gender and age. The benefits are significant especially
      in subjects with an elevated level of anxiety and depression because of more room
      for possible change. The most improvements are caused by rhythmic, aerobic
      exercises, using of large muscle groups (jogging, swimming, cycling, walking), of
      moderate and low intensity. They should be conducted for 15 to 30 minutes and
      performed a minimum of three times a week in programs of 10-weeks or longer. The
      results confirm the acute effect of exercise i.e. the reductions in anxiety and
      depression after single sessions of exercise. The changes in anxiety, depression
      and mood states after exercise are explained most frequently by the endorphin and
      monoamine hypotheses. Exercise may also increase body temperature, blood
      circulation in the brain and impact on hypothalamic-pituitary-adrenal axis and
      physiological reactivity to stress. The possible psychological mechanisms include
      improvement of self-efficacy, distraction and cognitive dissonance.

PMID- 15518310
TI  - [Depression syndromes in patients suffering from anorexia nervosa].
AB  - AIM: The purpose of the study was the estimation of comorbidity of depressive
      syndromes and anorexia nervosa (based on criteria of ICD-10 and DSM-IV). A group
      of 30 children (average age--13.5), 27 girls and 3 boys suffering from a first
      episode of anorexia nervosa was considered. METHOD: Anamnesis from patients and
      their parents, clinical observation, the psychiatric investigation with use of
      The Depression Rating Scale for Children (Elva o. Poznanski and comp.) and the
      Hamilton Depression Rating Scale. RESULTS: The comorbidity of depressive
      syndromes and anorexia nervosa was frequently observed. 73.3% children suffered
      from depressive syndromes in the course of anorexia nervosa. As for intensity--in
      33% it was moderate, in 20%--severe, and in 20%--mild depression. In the
      investigated group of children depressive syndromes appeared in the bulimic
      subtype of anorexia nervosa in 88.8% cases and in the restricting subtype in
      72.2%. Statistically, in the considered group, the depression was significantly
      frequent in the first and the second degree relatives. CONCLUSIONS: In the
      examined group, the number of biological as well as psychological events which
      could predispose to depression was found. However, the children were not
      suffering from depression until they were sick from anorexia nervosa and their
      bodies were not cachectic.

PMID- 15518311
TI  - [Assessment of quality of life of medical students relative to the number and
      intensity of depressive symptoms].
AB  - AIM: To assess the number and intensity of depressive symptoms in medical
      students of the Lodz Medical University as well as students of other faculties
      and to find the correlation between the intensity of depression and factors
      determining the quality of life. METHOD: Beck's Depression Inventory was applied
      to evaluate the depression intensity and the F. Baker and J. Intagliate Quality
      of Life Scale was used to find out about the life-quality. 177 2nd year and 86
      4th year medical students and 109 students from other faculties in Lodz, took
      part in the study. RESULTS: 28.8% of the 2nd year students and 14% of the 4th
      year medical students were diagnosed with depressive symptoms. A negative
      correlation between the depressive symptom intensity and a feeling of
      satisfaction with life was shown. Amongst the students of architecture and
      pedagogy, the depressive symptoms were above average for the general population.
      No statistically significant differences were noted amongst the groups of medical
      students and others in relation to the life perspectives, possibility of
      professional and personal development. CONCLUSIONS: To find the other causes of
      depression in the academic society, further research is necessary. This has a
      vital role for the protection of mental health of this specific professional
      group of people.

PMID- 15518312
TI  - [Trichotillomania. Its course and psychosocial consequences].
AB  - The article contains the definition and characteristics of trichotillomania, its
      prevalence, main syndromes and factors which intensify the pressure of
      uncontrolled hair pulling. It also raises the problem of the role of tension in
      maintaining these behaviours what is connected with some controversy around the
      definition of trichotillomania. In addition this article includes its
      relationship with other mental disorders. Special attention was given to the
      subjective experiences of chronic hair-pulling, and to social and psychological
      consequences of trichotillomania.

PMID- 15518313
TI  - [Coping with stress in those who experienced a traumatic situation].
AB  - AIM: Does the traumatic experience influence the choice of a particular coping
      style? If yes, which style is preferred by those who experienced trauma?
      Answering these two essential questions is the aim of this paper. The authors
      have accepted the assumption (Holman, Silver, 1998), that the individuals who
      experienced trauma prefer past temporal orientation and they present a higher
      level of distress. METHOD: The authors investigated two groups. The experimental
      group consisted of 46 victims of the Gdansk Shipyard concert hall fire. The
      control group comprised the 41 individuals who never experienced any trauma. Two
      psychological methods were used. CISS--Endler and Parker, which measures coping
      styles. STAI--Spielberger and al., was the second method used for measuring the
      level of anxiety as an essential distress indicator. RESULTS AND CONCLUSIONS: The
      results show, that individuals who experienced trauma, presented a significantly
      higher level of anxiety and that the victims of trauma prefer the emotional
      coping style. The difference is statistically significant. There is also an
      indirect conclusion (based on these results), which confirms the above mentioned
      assumption.

PMID- 15518314
TI  - [Psychological changes in the victims of the Gdansk Shipyard hall fire in the
      period of 1995-1999].
AB  - AIM: The aim of this paper was to answer two questions. First--has a particular
      traumatic event (the Gdansk Shipyard concert-hall fire) caused any
      psychopathological changes in the victims? Secondly--if yes, how do the dynamics
      of these changes manifest themselves? METHOD: The authors used two psychological
      methods. Adjective Check List, which measures the structure of psychological
      needs, and in some way, the picture of oneself (before and after the fire) and
      HADS-M, which measures the intensity of negative emotions (anxiety,
      depressiveness and aggression). The first investigation in 1995 included two
      groups: 46 victims of the fire and a control group (47 youngsters, who did not
      participate in this particular concert). The investigation of the victims group
      was then repeated twice, in 1996 (35 persons) and in 1999 (39 persons). RESULTS:
      The series of investigations lead to the conclusion that the traumatic event
      (Gdansk Shipyard hall fire) caused statistically significant, psychopathological
      changes in the victims (the first investigation). The changes concerned the
      worsening of the picture of oneself and an increase in the intensity of negative
      emotions (anxiety, depressiveness, aggression). All these changes still exist,
      despite the time which passed since the traumatic event (the repeated
      investigations).

PMID- 15518315
TI  - [Intensification of post-traumatic stress disorder of Siberian deportees from the
      North-East region of Poland].
AB  - AIM: Presentation of Post-Traumatic Stress Disorder based on the approach of
      various authors concentrating, upon the concept of the American classification:
      DSM III (1980) and DSM IV (1994). We acknowledged the necessity of displaying
      empirical results of intensification of PTSD among the Siberian deportees
      population in the region of North-East part of Poland. METHOD: In our analysis,
      we stressed the importance of the distant in time, psychological consequences of
      dwelling in extremely difficult living conditions that often threatened the life
      of those who had been deported to Siberia between 1939 and 1956. 40 "Siberian
      deportees" (20 men and 20 women) were examined. The method of PTSD-Interview
      (PTSD-I) was used here in order to obtain, in each individual case, the
      indicatory number indispensable for the statistical analysis. RESULTS AND
      CONCLUSION: An average result of PTSD intensification in the case of women
      reaches a "very significant" level and in the case of men it is even higher. The
      disparity between the average results of women and of men are statistically
      significant (p<0.05). This research has confirmed the assumptions that suffering
      from trauma in the early stage of development (within the age range of 8-15)
      leaves a permanent mark in the human psyche. Statistical analysis revealed a high
      level of intensification of PTSD among the population of the "Siberian deportees"
      from the North-East region of Poland.

PMID- 15518316
TI  - [Treatment methods in various stages of the pathway to psychiatric care].
AB  - AIM: The aim of this study was to analyse the treatment methods at the different
      stages of the pathway to psychiatric care. METHOD: In a period of two months all
      patients age 15 and over who applied to the Psychiatric Service in the Zabkowice
      catchment area and Psie-Pole catchment area were assessed by psychiatrists for
      their eligibility to enter the study. Those who had fulfilled the entry criteria
      were interviewed using a Polish version of WHO's encounter form (EF) by the
      mental health professionals during their initial interview. RESULTS: A total of
      228 patients (105 men and 123 women) were seen. Encounter forms were completed on
      200 people. 28 patients refused to answer some of the questions. There were
      significant differences in treatments offered to patients by hospital doctors and
      medical specialists, general practitioners (GP's) and psychiatrists. Our data
      show that sedative/hypnotics are the main psychotropic drugs prescribed by GP's.
      The small percentage of antidepressant (10% of all psychotropic drugs) used by
      GP's and medical specialists was noteworthy. They didn't decide to prescribe
      neuroleptics to their patients. CONCLUSIONS: The study revealed that GP's,
      hospital doctor & medical specialists prescribed antidepressant and neuroleptics
      far too rarely and GP's far too often prescribed sedative/hypnotics. This can
      indicate that they have difficulties in diagnosing of mental disorders as well as
      poor knowledge concerning indications relating the use of psychotropic drugs.

PMID- 15518318
TI  - [Object relation with drug--case report].
AB  - Psychoanalytic exploration of the action of psychotropic drugs has a long
      tradition which begins in the pioneer days of contemporary psychopharmacotherapy
      in 1950-ties. This exploration and publications based on them theorized about
      influence of neuroleptics on ego defences, id drives and intrapsychic conflicts
      and decrease in symptomatology as a result of action of the medication on all
      listed above. The paper presented is the case story about psychodynamic meaning
      of medication with a neuroleptic drug in a new context. The patient after a
      psychotic episode (paranoid type) was treated with quetiapine 600 mg per day and
      in the same time had an individual psychotherapy. During psychotherapy her
      inability to establish object stability was disclosed. In that particular
      intrapsychic situation the patient established a relation with an omnipotent and
      idealized representation of the drug. Medication was an absolutely idealized
      object for her one that was controllable and stabile and could not abandon her.
      The quality of relation with the drug was based on a primary defence mechanism
      like splitting, idealization and omnipotence and denial.

PMID- 15518317
TI  - [Nurses opinion on the necessity of educating psychiatric patients and their
      families].
AB  - AIM: To gather information on the need for educating psychiatric patients and
      their families by the nursing staff. METHOD: An anonymous questionnaire was
      especially constructed for this study. 628 nurses who worked in different health
      institutions (except for psychiatric departments) were asked to answer the
      questionnaire. RESULTS: Getting the patient ready for functioning in the normal
      world and showing him ways to cope with the illness were considered as the most
      important educational themes. It is disturbing to note that 14.01% of the
      responders did not answer this question at all. According to the nurses, the
      families should be educated well on how they should deal with their ill member.
      Most of those questioned declared a readiness to educate the ill, but only 31.8%
      of them felt only minimally prepared for the task. The best form of learning to
      be an educator were (according to 79.7% responders) training seminars in the
      preferable form of talks, lectures or lessons. The medical doctor should be the
      one who would help in the educational role. CONCLUSIONS: The majority of the
      nurses believe that they are not prepared well enough for this educational
      function. Only 4.5% of those studied did not show any need for educating patients
      and their families. Training seminars for nurses should be organized, so that the
      nurses feel competent to educate patients and their families. Interdisciplinary
      teams dealing with the issue of educating patients and their families should be
      formed.

PMID- 15518319
TI  - [Why schizophrenic patients use psychoactive substances?].
AB  - In the article the problems of prevalence of schizophrenic disorders and
      comorbidity with psychoactive substances such as drugs and alcohol were
      presented. This review summarizes the recent literature concerning: personality,
      schizophrenia and coming to decision to use psychoactive substances such as drugs
      and alcohol.

PMID- 15518320
TI  - [Oxidative stress in experimental acute glomerulonephritis].
AB  - The aim of this study was to estimate the concentration of lipid peroxidation
      products (TBARS -thiobarbituric acid reactive substances) in serum and in renal
      cortex, and erythrocytes superoxide dismutase (SOD), glutathione peroxidase (GPx)
      activity in blood during the development of experimental acute
      glomerulonephritis. Total antioxidant capacity of plasma and some of plasma
      nonenzymatic antioxidants, such as total protein level and uric acid were also
      measured. Acute glomerulonephritis was induced by intravenous injection of bovine
      serum albumin (BSA) in rabbits, at a dose of 250 mg/kg. Blood and tissues for
      analysis were taken from animals on the 2nd, 4th, 8th and 12th day after antigen
      administration. Morphologic changes in kidneys were verified by light and
      electron microscope. Injection of the BSA resulted in diffuse endocapillary
      proliferative glomerulonephritis with transient proteinuria with peak on the 8th
      day after antigen administration. Morphological alterations were associated with
      marked increase of TBARS in serum (on the 2nd, 4th, and 12th day) and renal
      cortex (on the 2nd, 4th and 8th day). In immunized rabbits we observed an
      increase in SOD activity (after 8 and 12 days of BSA injection). Activity of GPx
      was elevated throughout the observation period. We also noted an exhaustion of
      nonenzymatic antioxidants in plasma expressed as the decrease of total plasma
      antioxidant capacity (on the 2nd, 4th, 8th and 12th day), uric acid and total
      plasma protein level (8th day). We conclude, that during development of
      experimental acute glomerulonephritis, oxidative stress occurs which manifests as
      an increase of lipid peroxidation products, changes in antioxidant enzymes and
      exhaustion of nonenzymatic scavengers. The oxidant-antioxidant imbalance may
      contribute in the development of pathogenic changes in this model of
      glomerulonephritis.

PMID- 15518321
TI  - [The sperm quality in young patients before cancer therapy].
AB  - In the last years increasing incidence of malignant diseases in young men is
      observed. Sperm cryopreservation before cancer therapy gives the opportunity for
      these men to have a child in the future, but it is not know whether pretreatment
      sperm quality is sufficient to preserve fertility potential after thawing. The
      aim of this study was to compare the semen parameters (volume, total count,
      concentration, motility, morphology) in young cancer patients before treatment
      with healthy men, and examining the differences in sperm quality among patients
      group. Semen specimens were obtained from 81 patients with different neoplasms
      (testicular cancer n = 65, others n = 16 (Hodgkin's disease n = 11, lymphoma n =
      3, Ewing's sarcoma n = 1, osteosarcoma n = l1). Control group consisted of 43
      healthy males at similar age that came to our division as potential sperm donors.
      The total sperm count, concentration per ml, motility (grade A, B and C) and
      morphology were significantly lower in the cancer patients compared with normal
      men (p < 0.05), but still adequate for the future assisted reproductive
      technologies. Patients with testicular neoplasms had only significantly lower
      total sperm count and concentration in comparison with other cancer patients (p <
      0.05). Our results indicate that routine sperm banking should be offered for men
      before radio/chemotherapy to preserve future fertility.

PMID- 15518322
TI  - [Pediatric open heart surgery on cardiopulmonary bypass without the use of blood
      products].
AB  - Pediatric open heart surgery is associated with the usage of cardiopulmonary
      bypass. The circuit is primed with blood products because of risk of excessive
      hemodilution. The aim of the study was to prove the safety of open heart surgery
      on cardiopulmonary bypass without the use of blood products in the pediatric
      group. In this study, 78 patients with atrial septal defect (ASD type II) were
      enrolled and underwent elective atrial septal defect repair between the years of
      1999 and 2003. The group I included 37 children aged from 3 to 16 years (8.79 +/-
      4.45) who weighed from 13 to 68.8 kg (29.93 +/- 15.00). In this group, the
      transfusion of blood products during the surgery and postoperative course was
      avoided. Blood products were used in a control group (group II 4.1 patients) both
      during and after surgery. Children from this population ranged in age from 2.5 to
      17 years (8.41+/- 4.18) and weighed from 11.5 to 59.7 kg (26.99 +/-12.95). For
      statistical analysis the t-Student test and U Mann Whitney test were used. The
      length of stay in the intensive care unit (1.18 +/- 0.47 vs 1.20 +/- 0.61 days)
      and total hospital stay (8.91 +/- 3.05 vs 10.05 +/- 4.28 days) did not differ
      statistically between the groups. Values of haematocrit and hemoglobin levels
      were statistically lower in group I during the postoperative course compared to
      the control group (intraoperative Hct: 19.43 +/- 4.93 vs 23.37 +/- 4.68%, p <
      0.001), but these levels did not correlate with the occurrence of hypoxic,
      neurologic or coagulation complications. Directly after the surgery, group I had
      significantly higher platelet and leucocyte counts compared to the control group.
      There were no differences between the confronted populations in regard to
      postoperative bleeding (4.61 +/- 2.24 vs 4.76 +/- 1.75 ml/kg). The avoidance of
      using blood products in pediatric patients during open heart surgery with
      cardiopulmonary bypass is found to be safe, is not correlated with an increased
      surgical risk, and does not result in a prolonged hospital stay.

PMID- 15518323
TI  - [Electroglottography in patients operated for thyroid gland malignancies].
AB  - Electroglottography (EGG) was performed in 9 patients with vocal fold paresis
      (VFP) arisen after thyroid gland surgery performed for malignant tumours.
      Clinical symptoms, EGG waveforms and % Irregularity were analysed and correlation
      between dysphonia and % Irregularity computed. % Irregularity proved to be an
      effective measure of vocal fold dysfunction, significantly correlated with
      dysphonia.

PMID- 15518324
TI  - [Cardiovascular autonomic neuropathy and nephropathy in patients with type-1
      diabetes mellitus].
AB  - In the last few years much attention is being given to the problem of diabetes
      mellitus, to it's development, prevalence and progression of chronic
      complications. The aim of the study was to 1. evaluate correction of metabolic
      disturbances in patients with long-term type 1 diabetes mellitus; 2. evaluate
      occurrence of diabetic nephropathy and excretion function in patients with long
      term type 1 diabetes mellitus; 3. evaluate function of the cardiovascular
      autonomic nervous system in patients with long-term type 1 diabetes mellitus; 4.
      search for connections between the type and change dynamics in the cardiovascular
      system and degree of diabetic nephropathy advancement. The study was performed in
      a group consisting of 31 patients with type 1 diabetes mellitus (20 women, 11
      males). Mean age of the study group equaled 37.6 +/- 10.75 years, duration of
      diabetes mellitus 21.3 +/- 9.55 years. Concentration of cystatin C in the study
      group was 0.98 +/- 0.23 ng/ml, in the group of patients with diabetic retinopathy
      1.13 +/- 0.30 ng/ml, while in the group without diabetic retinopathy 0.89 +/-
      0.13 ng/ml. Concentration of cystatin C (p <0.05) and calculated GFR according to
      equations proposed by F.J. Hoeck [GFR/1.73 m2 = -4.32 + 80.3/plasma cystatin] (p
      < 0.01) also G.D. Tan [GFR -10 = (87.1/plasma cystine) - 6.87] (p < 0.01)
      significantly differentiated the discussed groups. CONCLUSIONS: despite normal
      levels of blood creatinine in the studied patients, decreased glomerular
      filtration was calculated for plasma cystatin C. Plasma cystatin C concentrations
      and calculated glomerular clearance significantly differentiated the group with
      retinopathy from the group without diabetic retinopathy. Determining cystatin C
      concentrations as a protein which probably does not undergo glycation in plasma,
      may play a role in the detection of early diabetic nephropathy, when as well as
      plasma creatinine levels and albumin/creatinine index calculated from a sample of
      morning urine do not differentiate the studied group of patients.

PMID- 15518325
TI  - [Cardiovascular diseases, medical apocalypse of the 21st century?].
AB  - The aim of this article is to bring forward and realise the size of
      cardiovascular diseases and the burden of its numbers that concern practising
      doctors in Lower Silesia, in Poland, Europe and the world. Every fourth patient
      knocking at the GP's door comes with a problem with the circulatory system. These
      diseases are the reason for every second in hospitalization or referral to a
      specialist. The most common diagnosis is not the common cold but arterial
      hypertension. Three of the most common diseases in patients over 65 years old
      are: hypertension, ischaemic heart disease, and atherosclerosis of the brain
      arteries. Poland belongs to the group of developed countries with an emerging
      economy, where degenerative diseases dominate, and cardiovascular diseases
      account for the biggest problems within the Health System. Nearly half of male
      deaths (46%) and over half of female deaths (56%) are the consequence of
      cardiovascular diseases. 80% of people around the world live in developing
      economies, where cardiovascular diseases cause 23% of all deaths. Every fifth
      person lives in a developed country and has a 50% chance of dying because of
      cardiovascular diseases. Will these diseases become "the number one killer" of
      the 21st century? 27% lost healthy life years are due to arterial hypertension,
      ischeamic heart disease, and congestive heart failure so their epidemiology is
      being regarded in this article.

PMID- 15518326
TI  - [Chlamydia pneumoniae and cardiovascular diseases].
AB  - The theories formulated to explain atherogenesis evolved from vessel wall lipid
      to endothelial dysfunction with vascular wall remodelling. Chlamydia pneumoniae
      has been demonstrated to play an important role in the development of
      inflammatory and immunological process and can initiate atherogenesis. This
      pathogen is found in atherosclerotic plaques, which can induce complex activation
      of local inflammatory and immunological events and lead to the development of
      unstable plaque, vascular remodelling and vessel lumen constriction.

PMID- 15518327
TI  - [Role of Chlamydia trachomatis infection in the pathology of male urogenital
      tract].
AB  - Based on literature data, the authors have presented the informations on
      epidemiology, pathogenesis, clinical picture, diagnostics and treatment of
      Chlamydia trachomatis urogenital infections in men.

PMID- 15518328
TI  - [Anthrax as a bioweapon].
AB  - The risk of biological and chemical terrorism is growing according to
      availability of modern biotechnologies and financial resources. The most potent
      biological weapon mentioned in the last decade is anthrax. The number of
      naturally acquired infections in humans is constantly reduced, however endemic
      areas are located in South and Middle Americas, South Europe, Asia and Africa. In
      any case of infection laboratory confirmation is indicated. Primary basic testing
      is available in all microbiology laboratories. In the current situation the
      medical and epidemiological infrastructure and microbiology diagnostics must be
      prepared for early and rapid coordinated action in order to detect and respond to
      biological and chemical attacks.

PMID- 15518329
TI  - [Use of oximes in the therapy of acute intoxication by organophosphorus
      compounds].
AB  - The treatment of patients who consumed lethal doses of various organophosphorus
      compounds (OP) still remains a great challenge to clinical toxicologists. The
      oximes in combination with atropine and diazepam are an integral part of the
      treatment of acute intoxications with organophosphate. Treatment with atropine,
      which relieves the muscarinic effects of acetylcholine and anticonvulsive agents
      (diazepam) is well established. However, the effectiveness of oxime compounds in
      counteracting the effect of intoxication in still a matter of debate. Based on
      literature reports, opinions are presented concerning the role of oximes in the
      treatment of intoxications by various OP.

PMID- 15518330
TI  - [Problem of HIV-infected patients receiving dialysis].
AB  - According to UNAIDS data there are 40 millions of HIV infected people in the
      world. 7880 people are infected with HIV (official statistics) in Poland. Because
      of improvement of dialysis accessibility in Poland there is no limitations of
      qualification for dialysis for HIV infected patients. In this article authors
      present general information about HIV infection (epidemiology, diagnostic,
      clinical picture and treatment), post exposure management and prophylaxis in
      dialysis centers. We present also algorithms of management with patient with
      acute/chronic renal failure in dependence on result of HIV test.

PMID- 15518331
TI  - [New measurement techniques in biology and medicine: atomic force microscopy
      (part III)].
AB  - Biological samples can be investigated with atomic force microscopy (AFM) in
      either of two imaging modes: contact mode or tapping mode. Applications of fluid
      tapping mode AFM in biology and medical sciences are constantly growing and the
      data obtained with this technique are improving, especially in terms of
      resolution. Even dynamic processes can be observed almost as they would occur in
      vivo. AFM is a proven imaging technique that has recently gained attention in
      biomaterials due to its ability to analyze surface properties, non-destructively
      at nanometer-level resolution in ambient air or in fluid environments.

PMID- 15518332
TI  - [Cutaneous lupus--current problem in dermatology].
AB  - A case of lupus vulgaris in 83-year-old woman is presented. Skin lesions appeared
      20 years earlier and till now were not treated. Cutaneous tuberculosis is a
      particular form of infection caused by Mycobacterium tuberculosis. Until recently
      tuberculosis occurred infected with human immunodeficiency virus a greater
      incidence of cutaneous tuberculosis is being observed.

PMID- 15518333
TI  - [Resection of the renal vein leiomyosarcoma with preservation of the kidney].
AB  - We present a case of 75 years old woman who successfully underwent resection of
      the right renal vein leiomyosarcoma (LMS-VR) with preservation of the kidney. It
      is the first reported case in Polish and fifth in world literature. The patient
      is alive without recurrence 24 months after operation. The surgical resection of
      LMS-VR with the preservation of the kidney should always be considered when the
      tumour does not infiltrate the renal hilus.

PMID- 15518334
TI  - A synthetic, non-peptide CXCR2 antagonist blocks MIP-2-induced neutrophil
      migration in mice.
AB  - Non-peptide antagonists of chemokine receptors are considered an intriguing
      alternative for the treatment of acute and chronic diseases. Particularly the
      recruitment of neutrophils to inflammatory sites often causes harmful side
      effects and is mediated by chemokine ligands of the CXC chemokine receptor 2
      (CXCR2). Hence, this receptor has been proposed as an important target for novel
      drugs. This study investigates the potential of the non-peptide CXCR2 antagonist
      SB 455821 to block neutrophil migration in mice. By using bone marrow derived
      neutrophils we established a migration assay which revealed SB 455821 as a potent
      inhibitor of macrophage inflammatory protein 2 (MIP-2)-induced neutrophil
      migration in vitro (IC50-20 nM). In vivo, injection of MIP-2 into the peritoneal
      cavities of mice markedly increased neutrophil numbers in peritoneal lavages
      which were reduced to control levels by co-administration of SB 455821 indicating
      that the compound effectively binds to the receptor under physiological
      conditions and exhibits biological activity in vivo. Nevertheless, using
      intraperitoneal injection of zymosan as a complex inflammatory stimulus, SB
      455821 was unable to block neutrophil recruitment to the peritoneal cavity of
      mice possibly due to other chemotactic mediators overruling signals derived from
      CXCR2 ligands. Our data show that SB 455821 blocks MIP-2-induced neutrophil
      migration in vitro and after injection in mice suggesting that selective CXCR2
      antagonists may be useful drugs in diseases where neutrophil accumulation plays a
      major role and leads to exacerbation of acute or chronic inflammations.

PMID- 15518335
TI  - Effect of pulmonary surfactant on TNF-alpha-activated endothelial cells and
      neutrophil adhesion in vitro.
AB  - Pulmonary surfactant given to infants and adults with respiratory failure is
      metabolized and recycled to a large extent. A small proportion also enters the
      circulation in cases of increased permeability of the alveolar-capillary
      membrane. We therefore investigated whether exogenous surfactants such as a
      natural bovine (natSF) or a synthetic (synSF) preparation had an impact on
      inflammatory conditions involving the adhesion of neutrophils to endothelial
      cells. Human umbilical cord vein endothelial cells (HUVEC) were plated on
      coverslips until confluence, activated by tumor necrosis factor-alpha and
      incubated with or without surfactant in the media. Human neutrophils passed the
      HUVEC layer in a flow chamber and interactions were visualized using a video
      microscope. To test if surfactant affected the expression of cell adhesion
      molecules, RT-PCR analyses were performed for E-selectin, vascular cell adhesion
      molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1). Using
      concentrations between 50 and 300 microg/ml of surfactant in the pre-incubation
      media the number of adherent neutrophils increased by 10-20% at the higher
      concentration of the natSF (*P < 0.05) whereas the synSF had no effect. Increased
      neutrophil adhesion was associated with a significant up-regulation of mRNA
      levels for E-selectin and VCAM-1; mRNA levels for ICAM-1, however, were not
      affected by the presence of surfactant. These observations indicate that natSF
      but not synSF might have pro-inflammatory effects when higher amounts of the
      exogenous dose reach the circulation. This might be explained by different fatty
      acid profiles, e.g. the presence of arachidonic acid in the natSF or higher
      concentrations of surfactant-associated protein-C in the synSF.

PMID- 15518336
TI  - New type of natural antibodies reactive to cytotoxic T lymphocyte-directed cancer
      vaccine peptides.
AB  - We recently reported the existence of antibodies (Abs) reactive to cytotoxic T
      lymphocyte-directed cancer vaccine peptides derived from non-mutated and
      proliferation-related self-proteins in the sera of healthy donors. The IgG class
      of these Abs was either lacking or unbalanced in atopic dermatitis patients,
      although the induction of a specific IgG by peptide vaccination was correlated
      with long survival in cancer patients, suggesting its positive role in the host
      defense. To understand the biological features of these Abs, we employed murine
      models due to the sequence homology of these peptides in human and mouse. Both
      IgM and IgG classes of these peptide-specific Abs were detected in all of the
      euthymic mice tested; however, only IgM was found in athymic nu/nu mice, and not
      in SCID mice. Maintenance of euthymic mice under germ-free conditions resulted in
      a lack of the IgG class of the Abs in these mice. Ab levels were found to
      increase with age-maturation, but they decreased under tumor bearing conditions
      or in cases of graft-versus-host disease. The Abs showed catalytic activity upon
      hydrogen peroxide (H2O2) production. These results suggest the existence of a
      novel type of natural Ab that is reactive to cancer vaccine peptides.

PMID- 15518337
TI  - Mls presentation by peritoneal cavity B cells.
AB  - DBA/2J spleen and peritoneal cells were compared for their ability to present the
      minor lymphocyte stimulatory superantigen Mls-1a. Although capable of Mls
      presentation in vivo, peritoneal cells were less effective than spleen cells in
      vitro. This difference was not due to cell concentration or culture duration.
      Flow cytometric comparison of spleen and peritoneal B cells revealed no
      significant differences in cell surface markers needed for cognate interaction
      with T cells. Resolution of peritoneal B cell subsets by cell sorting revealed
      that even though B-1 cells were capable of Mls presentation, they were less
      effective than B-2 cells. Mixing experiments showed that B-1 cells did not
      inhibit B-2 cell presentation of Mls. In contrast, total peritoneal cells
      inhibited T cell responses to Mls presented by spleen cells. The peritoneal
      cavity harbors B cells that can present Mls as well as other cells that can
      suppress this response.

PMID- 15518338
TI  - Preferential use of lambda light chains is associated with defective mouse
      antibody responses to the capsular polysaccharide of Neisseria meningitidis group
      B.
AB  - The capsular polysaccharide of Neisseria meningitidis group B (CpsB) is a very
      poor immunogen in mammals; this has been considered to be due to the induction of
      tolerance to cross-reactive host glycoconjugates. It has hampered the development
      of an effective vaccine against this meningococcal group for many years.
      Syngeneic populations have a similar tolerogenic background. Thus, we used the
      variability in ability to mount CpsB-specific immunoglobulin (Ig) responses of
      individuals from these populations to reveal underlying mechanisms to tolerance
      contributing to the poor immunogenicity of CpsB. Here we analyze by ELISA, the
      individual CpsB-specific Ig response of BALB/c and other syngeneic mice to
      immunization with intact bacteria, using the distribution of light chains as a
      direct indicator of the repertoire dynamics of the response. Although
      approximately 96% of anti-CpsB Ig bear kappa-light chains, BALB/c mouse
      populations were heterogeneous in the light chain composition of their individual
      anti-CpsB Ig responses. The proportion of kappa and lambda-light chains used for
      anti-CpsB Ig was a private characteristic that remained relatively constant, for
      each individual, through repetitive immunizations regardless of the bacterial
      stimuli size. Despite the prevalence of individual use of kappa-light chains, 5%
      of BALB/c mice showed restricted usage of lambda-light chains in their CpsB
      specific Ig responses, and an additional 11% use them significantly. The
      preferential use of lambda-light chains in these mice was strongly associated
      with defective IgM, and absent or barely detectable IgG anti-CpsB responses even
      after repetitive bacterial immunization. We conclude that differences in the
      private repertoire of specific Ig also contribute to mouse unresponsiveness to
      CpsB.

PMID- 15518339
TI  - Immunomodulating effects of cefodizime on Klebsiella pneumoniae-stimulated
      neutrophils.
AB  - To explore the immunoregulating effects of cefodizime on neutrophils and its
      mechanisms, we detected the expression of some cytokines secreted by neutrophils
      after heat-killed Klebsiella pneumoniae induced inflammation. We analyzed the
      changes of signal transduction in this process by detecting the mRNA expression
      of toll like receptor 4 (TLR4) and the inhibitor factor of kappaBalpha (I
      kappaBalpha) expressed by neutrophils. The activity of nuclear factor kappaB (NF
      kappaB) in neutrophils was also assayed by electrophoretic mobility shift assay
      (EMSA). We found cefodizime increased neutrophil production of TNF-alpha, IL
      1beta in the early stage of inflammation, which was in agreement with the
      enhanced mRNA expression of TLR4 and DNA-binding activity of NF-kappaB. Taken
      together, the immunomodulating effects of cefodizime on cytokine production of K.
      pneumoniae stimulated neutrophils is possibly due to its regulation of TLR4 mRNA
      expression and DNA binding activities of NF-kappaB through the LPS-TLR4-NF-kappaB
      pathway.

PMID- 15518340
TI  - UL16 binding proteins.
AB  - According to present concepts, innate immunity plays an important role in tumor
      surveillance and immune modulation. The state of NK cells depends on the balance
      between inhibitory and activating signals from corresponding receptors. As one of
      the activating receptors, NKG2D recognises some self ligands such as MICA/B in
      human and Rae1 in mice, which is dissimilar to those toll-like receptors that
      recognise some pathogen-derived ligands. NKG2D is expressed not only on NK cells,
      but on gammadelta T cells, CD8+ alphabeta T cells in normal individuals and CD4+
      alphabeta T cells in rheumatoid arthritis patients and plays a different role on
      respective cells. Whereas NKG2D can only function as a costimulatory receptor on
      CD8+ alphabeta T cells under the domination of alphabeta TCR in spite of a
      deficiency of costimulatory molecule CD28, NKG2D can directly activate NK cells
      even in the presence of inhibitory signals from MHC-I and corresponding receptor
      complexes. Experiments in mice have identified that alternative splicing produces
      two distinct NKG2D polypeptides that associate differentially with the DAP10 and
      DAP12 signaling subunits and that differential expression of these isoforms and
      of signaling proteins determines whether NKG2D only functions as a costimulatory
      receptor in the adaptive immune system (CD8+ T cells) or as both a primary
      recognition unit and a costimulatory receptor in the innate immune system
      (natural killer cells and macrophages). This review summarizes the research
      achievements in a new ligand family (UL16 binding proteins) of NKG2D in human and
      shows the possible prospects of ULBP function and application.

PMID- 15518341
TI  - Penicilliosis in China.

PMID- 15518342
TI  - Fifteen cases of penicilliosis in Guangdong, China.
AB  - We analyzed the occurrence, clinical and physical features, laboratory findings,
      diagnostic criteria, reaction to therapy and prognosis of 15 cases Penecilliosis
      marneffei. Four were localized infection on skin, eleven were systemic infection,
      all cases were found in Guangdong province of China. We found that males were
      predominant in infection compared with females in 15 patients, and all patients
      observed had different occupations. The patients with AIDS as underlying disease
      were commonly drivers or unemployed. Thirteen of 15 patients had underlying
      diseases, i.e., connective tissue disease, aplastic anemia, kidney transplant,
      AIDS. Clinical features showed different symptoms, including weight loss, high
      fever, skin lesions, and respiratory system symptoms. Seven of 15 patients
      received antifungal therapy, the remaining eight patients did not receive therapy
      for different reasons. Nine of the patients died five recovered. Fifteen isolates
      were cultured from skin lesions, blood, bone marrow, peritoneum dialysis and
      pleural effusion and were confirmed to be Penicillium marneffei by morphology,
      thermal dimorphism, pathology and DNA sequence analysis. This report indicates
      that Penicillium marneffei may exist in nature in Guangdong province of SE China.

PMID- 15518343
TI  - Anti-rhinosporidial antibody levels in patients with rhinosporidiosis and in
      asymptomatic persons, in Sri Lanka.
AB  - The only report hitherto, from India in 1982, on anti-rhinosporidial antibody
      levels in patients with rhinosporidiosis recorded that antibody was not detected
      in Indian patients. The present report describes the use of the dot-ELISA assay
      of serum anti-rhinosporidial IgG, IgM and IgA and salivary sIgA in patients with
      diverse clinical presentations, in rural asymptomatic persons who had bathed in
      ground waters that probably harboured the causative pathogen, Rhinosporidium
      seeberi, and in laboratory persons who were exposed to R. seeberi. Ultrasonic
      extracts of purified endospores and sporangia of R. seeberi were used as antigen.
      The geometric mean (reciprocal) titres of serum antibody detected in patients
      were IgM 142.1, IgG 178.5, IgA 84.6, with ranges of 0-640, 30-960 and 0-160
      respectively, salivary sIgA titres ranged from 0 to 18 with a mean of 4.6. The
      levels of antibody had no correlation with the site, the number of sporangia,
      duration and recurrence of the disease. Asymptomatic persons from the same
      endemic area as patients showed mean titres of IgM 89.6, IgG 69.1, IgA 95.5, with
      salivary sIgA titres of 3.1. Asymptomatic personnel who had been working in a
      laboratory where rhiniosporidial work was being done, showed mean titres of 169.6
      IgM, 62.8 IgG, and 6.5 salivary sIgA. These results indicate that an anti
      rhinosporidial antibody response occurs in rhinosporidial patients, as well as in
      asymptomatic persons who were exposed to R. seeberi in the environment. Anti-R.
      seeberi antibody does not appear to be protective in rhinosporidiosis since
      appreciable titres were present in patients with recurrent, single, multiple or
      disseminated lesions of long duration.

PMID- 15518344
TI  - Voriconazole proves effective in long-term treatment of a cerebral cryptococcoma
      in a chronic nephropathic HIV-negative patient, after fluconazole failure.
AB  - Although being a rare occurrence, brain cryptococcoma may represent an emerging
      issue, because of its relationship with a broadening range of risk factors,
      including malignancies, neutropenia, end-organ failure, bone marrow and solid
      organ transplantation, and multiple underlying causes of primary-secondary
      immunodeficiency. A cerebral cryptococcoma in a chronic nephropathic HIV-negative
      subject with homocystinuria, completely cured with neurosurgery and voriconazole
      after fluconazole failure, is described.

PMID- 15518345
TI  - Trichoderma spp. antagonism to the dermatophyte Trichophyton rubrum: implications
      in treatment of onychomycosis.
AB  - Onychomycosis--the dermatophytic invasion of the nail--is difficult to eradicate
      with drug treatment. The hyphae of the main invading pathogen, Trichophyton
      rubrum, are often interwoven with the nail plate, preventing effective anti
      mycotic agents from reaching its growing tips. An alternative approach to treat
      onychomycosis may possibly be the application of a biological control agent
      against the pathogen. In analogy with the success of biocontrol of
      phytopathogenic fungi, we screened a series of commercially available Trichoderma
      strains for potential antagonism between Trichoderma and Trichophyton spp. A wide
      spectrum of antagonism capacity, ranging from effective overgrowth to no
      interaction was found, with Trichoderma virens NRRL 26672 being the most
      effective against the Trichophyton strains tested e.g. T. rubrum NCPF118.
      Furthermore, T. virens NRRL 26672 grown with T. rubrum NCPF118 hyphae as a carbon
      source, exhibited enhanced induced secretion of active extracellular chitinases
      and beta-glucosidases, affecting lysis and sporulation on T. rubrum NCPF118
      hyphae. Growth of Trichod. virens NRRL 26672 in poor medium also resulted in
      secretion of antibiotics active in arresting the growth of T. rubrum NCPF118
      inoculum. Our findings may open new directions for the treatment of
      onychomycosis, either in combination with known medications or as a new "natural"
      route.

PMID- 15518346
TI  - Onychomycosis in Cali, Colombia.
AB  - This study presents the epidemiological and mycological aspects of 299 patients
      with nail lesions who were referred to three diagnostic laboratories in the city
      of Cali. The diagnosis of mycoses was established through visualization of
      mycotic structures in a direct microscopic examination of skin scrapings and by
      isolation. Onychomycosis was found in 183 cases (61.2%), of which 141 were in
      toenails (44 in males and 97 in females), 38 in fingernails (9 males and 29
      females), and 4 cases in toenails and fingernails simultaneously (all females).
      No statistically significant relation was found between sex and onychomycosis.
      Yeasts accounted for 40.7% of the mycoses, dermatophytes for 38%, nondermatophyte
      molds for 14% and the etiology was mixed in the remaining cases (7.3%). Candida
      albicans was the most commonly isolated yeast species; the most common
      dermatophyte was Trichophyton rubrum and Fusarium spp. and Scytalidium dimidiatum
      were the most common nondermatophytic molds. Them common fungi found in
      fingernails were yeasts; in toenails dermatophytes were more prevalent (chi2 with
      Yates' correction = 19.75, P= 0.000088). Yeasts were observed more frequently in
      females while dermatophytes were more common in males. The difference between
      these two etiologic groups was statistically significant (chi2 with Yates'
      correction = 7.43, P = 0.0064); no relation was observed according to age.

PMID- 15518347
TI  - Electrophoretic variants of intracellular catalase of different Candida species.
AB  - Intracellular and extracellular catalases of different species of Candida were
      investigated using different culture media. All the Candida strains produced
      intracellular catalase, whose enzymatic activity was detected by non-denaturating
      polyacrylamide gradient (4-30%) gel electrophoresis. The cell extracts presented
      a major 230 kDa catalase band and in some strains variants of catalase with
      different molecular weights were detected. Candida catalase activity was not
      affected by heating at 50 degrees C and incubation with beta-mercaptoethanol, but
      treatment with sodium dodecyl sulphate inhibited or reduced enzymatic activity.
      Extracellular enzyme activity was not detected in any of the culture filtrate
      extracts tested.

PMID- 15518348
TI  - Cryptococcus neoformans varieties from material under the canopies of eucalyptus
      trees and pigeon dropping samples from four major cities in Jordan.
AB  - To our best knowledge, any study related to the ecological distribution of
      Cryptococcus neoformans in Jordan does not exist in the medical literature. In
      order to determine the environmental occurrence of both varieties of Cryptococcus
      neoformans in Jordan, pigeon droppings and material under the canopies of
      eucalyptus trees were collected from four major cities of this country. For the
      isolation of Cryptococcus neoformans variety gattii from environmental sources,
      500 samples of the mixed soil debris, including tree materials, under the
      eucalyptus trees from cities of Amman, Irbid, Jerash, and Ajlun were collected.
      Also, 509 samples of pigeon droppings were collected from the same cities for the
      isolation of Cryptococcus neoformans variety neoformans. After inoculating the
      samples onto modified Staib agar medium in Petri dishes, a total of 336 melanoid
      yeast colonies were picked up during screening process. At the end of serial
      mycological studies, none of these isolates was identified as Cryptococcus
      neoformans, but all were Cryptococcus species other than C. neoformans. For
      determining the exact status, more extensive environmental studies need to be
      done in the future.

PMID- 15518349
TI  - A pilot-scale expressed sequence tag analysis of Beauveria bassiana gene
      expression reveals a tripeptidyl peptidase that is differentially expressed in
      vivo.
AB  - The entomopathogen Beauveria bassiana is a dimorphic fungus that displays an in
      vivo-specific, yeast-like parasitic phase. In order to study the transcriptome of
      B. bassiana during this unique developmental phase, we developed a method to
      harvest in vivo B. bassiana cells from infected Manduca sexta larvae. The
      infected hemolymph was collected just prior to insect death and subjected to
      gradient centrifugation, which allowed for separation of the B. bassiana in vivo
      produced cells from remaining insect hemocytes. Total RNA was extracted from the
      harvested fungal cells and used to construct a cDNA library that is
      representative of B. bassiana gene expression in vivo. Expressed Sequence Tags
      (ESTs) were generated and led to the cloning of two protease genes. One of these
      proteases was identified as a tripeptidyl peptidase (Bb TPP). The Bb TPP protease
      was shown to be up-regulated during infection, and identification of a signal
      peptide suggested that the enzyme is secreted in the host hemolymph. Although its
      activity and role have yet to be characterized, the Bb TPP protease appears as a
      likely candidate for being involved in B. bassiana pathogenesis. The
      identification of this novel, up-regulated protease also suggests that random
      sequencing from our in vivo cDNA library may be a valuable step towards
      identifying biologically active metabolites produced in vivo by B. bassiana.

PMID- 15518350
TI  - A proposed role for the cuticular fatty amides of Liposcelis bostrychophila
      (Psocoptera: Liposcelidae) in preventing adhesion of entomopathogenic fungi with
      dry-conidia.
AB  - Maximum challenge exposure of Liposcelis bostrychophila to Beauveria bassiana,
      Paecilomyces fumosoroseus, Aspergillus parasiticus or Metarhizium anisopliae
      resulted in no more than 16% mortality. We investigated several of L.
      bostrychophila's cuticular lipids for possible contributions to its tolerance for
      entomopathogenic fungi. Saturated C14 and C16 fatty acids did not reduce the
      germination rates of B. bassiana or M. anisopliae conidia. Saturated C6 to C12
      fatty acids that have not been identified in L. bostrychophila cuticular extracts
      significantly reduced germination, but the reduction was mitigated by the
      presence of stearamide. Cis-6-hexadecenal did not affect germination rates.
      Mycelial growth of either fungal species did not occur in the presence of
      caprylic acid, was reduced by the presence of lauric acid, and was not
      significantly affected by palmitic acid. Liposcelis bostrychophila is the only
      insect for which fatty acid amides have been identified as cuticular components.
      Stearamide, its major fatty amide, did not reduce germination of B. bassiana or
      M. anisopliae conidia or growth of their mycelia. Adhesion of conidia to
      stearamide preparations did not differ significantly from adhesion to the cuticle
      of L. bostrychophila. Pretreatment of a beetle known to be fungus-susceptible,
      larval Oryzaephilus surinamensis, with stearamide significantly decreased
      adhesion of B. bassiana or M. anisopliae conidia to their cuticles. This evidence
      indicates that cuticular fatty amides may contribute to L. bostrychophila's
      tolerance for entomopathogenic fungi by decreasing hydrophobicity and static
      charge, thereby reducing conidial adhesion.

PMID- 15518351
TI  - Regulation of aflatoxin synthesis by FadA/cAMP/protein kinase A signaling in
      Aspergillus parasiticus.
AB  - Analysis of fadA and pkaA mutants in the filamentous fungus Aspergillus nidulans
      demonstrated that FadA (Galpha) stimulates cyclic AMP (cAMP)-dependent protein
      kinase A (PKA) activity resulting, at least in part, in inhibition of conidiation
      and sterigmatocystin (ST) biosynthesis. In contrast, cAMP added to the growth
      medium stimulates aflatoxin (AF) synthesis in Aspergillus parasiticus. Our goal
      was to explain these conflicting reports and to provide mechanistic detail on the
      role of FadA, cAMP, and PKA in regulation of AF synthesis and conidiation in A.
      parasiticus. cAMP or dibutyryl-cAMP (DcAMP) were added to a solid growth medium
      and intracellular cyclic nucleotide levels, PKA activity, and nor-1 promoter
      activity were measured in A. parasiticus D8D3 (nor1::GUS reporter) and TJYP1-22
      (fadAGA2R, activated allele). Similar to Tice and Buchanan [34], cAMP or DcAMP
      stimulated AF synthesis (and conidiation) associated with an AflR-dependent
      increase in nor-1 promoter activity. However, treatment resulted in a 100-fold
      increase in intracellular cAMP/DcAMP accompanied by a 40 to 80 fold decrease in
      total PKA activity. ThefadAG42R allele in TJYP1-22 decreased AF synthesis and
      conidiation, increased basal PKA activity 10 fold, and decreased total PKA
      activity 2 fold. In TJYP1-22, intracellular cAMP increased 2 fold without cAMP or
      DcAMP treatment; treatment did not stimulate conidiation or AF synthesis. Based
      on these data, we conclude that: (1) FadA/PKA regulate toxin synthesis and
      conidiation via similar mechanisms in Aspergillus spp.; and (2) intracellular
      cAMP levels, at least in part, mediate a PKA-dependent regulatory influence on
      conidiation and AF synthesis.

PMID- 15518352
TI  - Structural and ultrastructural alterations in BALB/c mice: effects of Penicillium
      citrinum metabolites.
AB  - The aims of this work were to determine the effect of feeding BALB/c mice a diet
      containing culture materials of a citrinin producing strain of Penicillium
      citrinum (Thom). Changes in hematological parameters, serum chemistry and
      histological changes in liver, kidney and heart were determined. After 60 days,
      control treated (CT) mice appeared normal in all respects, whereas, the mice fed
      the feeds supplemented with Penicillium (CMT) showed decreased weight gain, lower
      hematocrits, increased serum alanine aminotransferase (ALT) and clear signs of
      renal and hepatotoxicity based on histological changes. Changes observed in the
      liver of CMT mice included portal and lobular infiltration of polymorphonuclear
      cells, with concomitant hepatocellular necrosis, hepatic steatosis, prominent
      Kupffer's cells, hemosiderin granules in the cytoplasm of periportal hepatocytes
      and other lipid inclusions in the surrounding mitochondria were also observed.
      Our findings suggest that in vivo, P. citrinum Thom metabolites, which contain
      citrinin, could cause illnesses such as toxic hepatitis or intravascular
      hemolysis.

PMID- 15518353
TI  - Contamination of aflatoxins in herbal medicinal products in Thailand.
AB  - Twenty-eight herbal medicinal products from Thailand were investigated for
      aflatoxin (AF) contaminations by employing a specific HPLC assay for the
      determination of AFB1, B2, G1 and G2. The samples were extracted with 80% (v/v)
      methanol in water before further cleaned up with an immunoaffinity column and
      followed by the detection of AFs by using an electrochemically post-column
      derivatization with iodine and fluorescence detector. The extraction procedure
      was optimized in order to obtain the best recovery. The method was successfully
      carried out with all the herbal products diversified as to compositions and
      dosage forms. The results revealed that five (18%) of herbal samples were
      contaminated with detectable amount of the total AFs ranging from 1.7 to 14.3
      ng/g. The association between particular herbal/plant and the AF contaminated
      could not be determined due to the low frequency of positive samples. The
      contaminated products were those in tablet (4) and capsule (1) dosage forms. It
      was possible that the original fungal infection of these products may have been
      derived from either the crude herbal or other ingredients making these
      preparations, such as starch. In conclusion, none of the AF contaminated level
      found was above the current legislative level permissible in Thailand (20 ng/g).
      A word of caution, however, exporting some high AF-contaminated herbal products
      to countries where more stringent permissable level of aflatoxins exist could
      result in trade Barriers.

PMID- 15518354
TI  - Investigation of fungal contamination in sheep and goat cheeses in southern
      Italy.
AB  - One hundred and twenty-two samples of cheeses made from goat and sheep milk and a
      mixture of the two types, produced in Southern Italy by industrial establishments
      or artisans, were analysed for the detection of fungal contamination and the
      presence of potentially toxigenic moulds. Only organoleptically acceptable
      cheeses without evident fungal contamination were studied. Among these, 40 were
      unripened, 30 medium and 52 long ripened cheeses. Moulds were found in 54 of the
      122 analysed samples (44.3%). The most contaminated cheeses were the medium and
      long ripened ones (46.3% and 35.2%), and the industrial cheeses (59.1%). The
      artisan cheeses were the least contaminated (26.8%). Among the cheeses that
      tested positive, Penicillium species were the most frequently isolated (72.9%),
      followed by Geotrichum spp. (7.3%), Aspergillus spp. (4.2%) and Mucor spp.
      (4.2%). The potentially toxigenic species within the genera Penicillium,
      Aspergillus and Fusarium were mainly detected in sheep cheeses.

PMID- 15518355
TI  - Morphological variation and host range of two Ganoderma species from Papua New
      Guinea.
AB  - Two species of Ganoderma belonging to different subgenera which cause disease on
      oil palms in PNG are identified by basidiome morphology and the morphology of
      their basidiospores. The names G. boninense and G. tornatum have been applied.
      Significant pleiomorphy was observed in basidiome characters amongst the
      specimens examined. This variation in most instances did not correlate well with
      host or host status. Spore morphology appeared uniform within a species and spore
      indices varied only slightly. G. tornatum was found to have a broad host range
      whereas G. boninense appears to be restricted to palms in Papua New Guinea.

PMID- 15518356
TI  - Introduction to the American Hospital Quest for Quality Prize.

PMID- 15518357
TI  - Sentara Norfolk General Hospital: accelerating improvement by focusing on
      building a culture of safety.
AB  - BACKGROUND: To accelerate progress in improving patient safety, Sentara Norfolk
      General Hospital (SNGH) supplemented its improvement programs with an initiative
      to strengthen its organizational culture of safety. CREATING A CULTURE OF SAFETY:
      SNGH established and intternalized behaviors in the organization that would
      result in safer and more reliable and productive human erformance. Four areas of
      focus were identified: (1) creating Behavior-Based Expectations (BBEs) for error
      prevention for all positions, (2) establishing Red Rules to focus employees on
      rules with the highest level of consequence and risk if not followed exactly, (3)
      develping a technically based Root Cause and Common Cause Analysis process, and
      (4) implementing an appproach to focus and simplify policies and procedures. KEYS
      TO SUCCESS: The senior leadership made the safety initiative the number-one
      priority; operational goals were prioritized to ensure the availability of time
      and resources for the safety initiative. A team of five operational leaders led
      implementation and ensured efffective communication across the organization.
      Medical staff provided support to the safety initiative; for example, it
      developed and implemented its own BBEs list. Finally, employees were engaged in
      all phases of the initiative. SNGH's largest challenge remains to continue to
      accelerate improvement while simultaneously holding gains previously made.

PMID- 15518358
TI  - The Johns Hopkins Hospital: identifying and addressing risks and safety issues.
AB  - BACKGROUND: At The Johns Hopkins Hospital (JHH), a culture of safety refers to
      the presence of characteristics such as the belief that harm is untenable and the
      use of a systems approach to analyzing safety issues. PATIENT SAFETY AS A
      LEADERSHIP AND ORGANIZATIONAL PRIORITY: The leadership of JHH provides strategic
      planning guidance for safety and improvement initiatives, involves the patient
      safety committee in capital investment allocation decisions and in designing and
      planning new hospital facilities, and ensures that safety and quality head the
      agenda of board-of-trustees meetings. Although JHH takes a systems approach,
      structures such as monitoring staff behavior trends are used to hold people
      accountable for job performance. CHALLENGES AND LESSONS LEARNED: JHH encountered
      three major hurdles in implementing and sustaining a culture of safety. First,
      JHH's decentralized organizational structure contributes to a silo effect that
      limits the spread of ideas, practices, and culture. JHH intends to create an
      internal collaborative of departmental safety initiatives to foster opportunities
      for units to share ideas and results. Second, in response to the challenge of
      encouraging teams to think and act in an interdisciplinary fashion, communication
      and teamwork training are being used to enhance the effectiveness of
      interdisciplinary teams. Further development of valid and meaningful safety
      related measurement and data collection methodologies is JHH's largest remaining
      challenge.

PMID- 15518359
TI  - Mary Lanning Memorial Hospital: communication is key.
AB  - BACKGROUND: Mary Lanning Memorial Hospital (MLMH) defines a culture of safety "as
      a pattern of behavior, both individual and organizational, and an underlying
      philosophy that seeks to minimize hazards and harm to patients that result from
      the processes of care." The hospital's strategic plan designates quality of care
      as its first priority, and one of its two priority goals is "To continue to
      identify and implement patient safety initiatives that will positively affect
      care delivery processes while minimizing patient safety errors, defects, and
      sentinel events, and striving for zero defects." PATIENT SAFETY AS A LEADERSHIP
      AND ORGANIZATIONAL PRIORITY: An occurrence in 2000 highlighted the need for a
      standardized medication administration process. It is anticipated that the
      ongoing bar-code point-of-care technology project will significantly reduce
      medication administration errors as they relate to the five rights, better
      capture near-miss data for further analysis, and increase nursing personnel time
      efficiency. CHALLENGES AND LESSONS LEARNED: MLMH has experienced three
      significant challenges in implementing and sustaining a culture of safety. First,
      as the central component of all patient safety activities, communication requires
      constant vigilance. Second, on the basis of the experience, for example, with the
      bar-code point-of-care technology project, introducing technology presents a
      variety of challenges. Third, although many patient safety initiatives can be
      accomplished with minimal funding, large-scale initiatives usually necessitate a
      significant financial commitment.

PMID- 15518360
TI  - Advocate health care: a systemwide approach to quality and safety.
AB  - BACKGROUND: Advocate Health Care's culture of safety is rooted in its mission,
      values, and philosophy and demonstrates a profound regard for the welfare of
      those it serves. Its five values--excellence, compassion, partnership, equality,
      and stewardship--provide the foundation for interactions with patients. PATIENT
      SAFETY AS A LEADERSHIP AND ORGANIZATIONAL PRIORITY: Patient safety has been a
      leadership and organizational priority since 1999, when the chief executive
      officer and chief medical officer appointed an eight-member patient safety task
      force. The treatment of patient safety as a priority is reflected, for example,
      in sustained support for the patient safety task force's four teams (labor and
      delivery, nosocomial infection prevention, medication error prevention, and
      delayed/missed diagnoses), in the allocation of significant financial resources
      to technology, and in the dedication of additional capital to create safer
      physical-facility designs. CHALLENGES AND LESSONS LEARNED: To implement and
      sustain a culture of safety, Advocate addressed three challenges: complexity of
      the system, underreporting of patient safety events, and medical staffs
      acceptance of the disclosure policy. For example, strategies to address the
      underreporting challenge include creating a standardized patient safety event
      form, integrating disparate databases for patient safety event reporting, and
      providing ongoing education to reinforce the need to report events. Advocate's
      most significant area for improvement is to become less reliant on risk reduction
      strategies that may result only in short-term improvements.

PMID- 15518361
TI  - Methodological issues in public reporting of patient perspectives on hospital
      quality.
AB  - BACKGROUND: Increasing attention is being focused on public reporting of patient
      satisfaction and experience with hospital care, both nationally and at the state
      level. Comparative reports on hospital patient satisfaction use a standard
      survey, but little is known about underlying methodological approaches for
      reporting these quality measures. METHODS: Literature, Web sites, and key
      informants were used to identify nine public reports. In-depth reviews were
      conducted to determine approaches to collecting, analyzing, and publicly
      reporting comparative data. Data were grouped into four analytic categories:
      survey, sampling, computation of scores, and reporting of scores. RESULTS: The
      reports were similar in response rates and sampling procedures but differed in
      the number of hospitals included, the survey instrument, and survey procedure.
      The reports varied considerably in the techniques for computing hospital scores
      and decisions about reporting scores. CONCLUSIONS: Reports from nine locales
      illustrate the decision making necessary to produce comparative reports on
      hospital patient satisfaction. Differences stem from decisions about the survey
      instrument and statistical decisions about how to interpret and report data.
      These issues should be clearly delineated as part of any public reporting
      process.

PMID- 15518362
TI  - Poor interface design and lack of usability testing facilitate medical error.
AB  - BACKGROUND: A fictional scenario based on a compilation of several real events
      describes seven medical errors that at first appear to be caused by the
      paramedics and nurses involved. HUMAN FACTORS ENGINEERING (HFE) ANALYSIS: An
      emergency medical services paramedic attempted to use a debrillator on a 67-year
      old man with ventricular tachycardia Yet nothing happened. The defibrillator
      displayed an indication that it was in synchronized mode but provided no feedback
      to tell the user that it was not prepared to shock because of low QRS amplitude.
      USABILITY TESTING: A hands-on approach to discovering the difficulties and
      potential for error that people encounter when trying to use a product, usability
      testing can help to create medical devices and systems that are not only more
      "user friendly" and efficient-but safer. RECOMMENDATIONS: Recommendations are
      presented to enable health care leaders to apply human factors considerations in
      their product evaluation and purchasing decisions. Medical device manufacturers
      should involve human factors engineers in the design process from the outset and
      should perform usability testing. Health care organizations should expect an
      optimized and tested user interface in the medical devices they purchase.
      SUMMARY: Many adverse events in medicine are the result of poor interface design
      rather than human error. The HFE concepts of usability and standardization are
      critical to patient safety.

PMID- 15518363
TI  - Adult acute lymphoblastic leukemia.

PMID- 15518364
TI  - Role of estrogens in the secondary hormonal manipulation of hormone refractory
      prostate cancer.
AB  - OBJECTIVE: To evaluate the role of Estrogens (Honvan) in the secondary hormonal
      manipulation of patients with hormone refractory prostate cancer (HRCP). METHODS:
      Twelve patients diagnosed as hormone refractory prostate cancer received
      intravenous estrogens for six days (Fosfestrol, a synthetic phosphorylated
      estrogen derivative), followed by a maintenance oral dose of 120 mg thrice daily
      as second line hormonal treatment. During the treatment they were given deep
      venous thrombosis prophylaxis. Their stage at initial presentation, primary
      treatment, mode of androgen ablation, prostate specific antigen (PSA) level,
      duration of remission prior of HRPC status, PSA doubling time before and after
      estrogen treatment were recorded. The morbidity and mortality of the treatment
      was also recorded. A drop in PSA of > 50% was classified as major responder. The
      drop of < 50% was defined as minor responders. Treatment failure was defined as a
      rise in PSA > the level prior to the start of treatment. RESULTS: The mean age at
      diagnosis of prostate cancer was 66.6 + 5.4 years (range 57-73). At the time of
      initial diagnosis only 3 patients (25%) had localized disease and 9 (75%) had
      metastatic prostate cancer. Six patients each opted for surgical or medical
      castration (LHRH analogs) as the mode of androgen ablation. The mean initial PSA
      at diagnosis was 340 + 728.1 ng/ml (range 4.1-2375, Median 94). After development
      of HRPC, six patients (50%) had major response, four (33%) had minor response to
      estrogen administration. Two patients (17%) did not respond to estrogens. The
      mean PSA before receiving Fosfestrol was 60.5 + 82 ng/ml (range 0.013-246). The
      PSA (nadir) after treatment was 24.3 +/- 33.2 ng/ml (range 0.9-81.3). One patient
      developed gynaecomastia and one had congestive cardiac failure. Two patients died
      of non cancer related deaths and one patient died of cancer related death.
      CONCLUSION: Synthetic estrogens are well tolerated, in-expensive agents and could
      be considered for palliative use against hormone resistant prostate cancer.

PMID- 15518365
TI  - Socioeconomic status and breast cancer survival in Pakistani women.
AB  - OBJECTIVES: No data is available from developing countries correlating
      socioeconomic status (SES) with survival in female breast cancer patients. We
      decided to test the hypotheses whether SES is an independent determinant for
      disease stage, access to minimal expected treatment (MET) and survival. METHODS:
      Two hundred eighty six patients diagnosed with breast cancer were recruited
      between April 1996 to May 1998. Patients were divided into three groups according
      to their SES. Prognostic factors analyzed were age, tumor size, nodal status;
      stage at presentation, estrogen receptor status, time elapsed before diagnosis
      and access to MET. Disease free survival (DFS) and overall survival (OS) were
      determined according to the SES of the patients. RESULTS: Patients were
      categorized into three socioeconomic groups, high (21%), middle (44%) and low
      (35%). Mean age of all patients was 46 years, in patients from lower SES mean age
      was 43 years compared to 50 years in high SES. Mean time elapsed before diagnosis
      for women from high-income group was 4.3 months versus 10.6 months in low-income
      group. Early breast cancer was more common in affluent strata, 70% versus 41% in
      the lower strata. Eighty-nine percent patients received MET from the affluent
      group compared to only 43% patients in the lower strata. Literacy rate of
      patients from high SES was 73.7% compared to 15% in the low SES. Five year DFS
      and OS are 79% and 86% for high income group, 48% and 68% for middle income group
      and 31%,49% for lower strata which were statistically significant (P=.0001 and
      P<.0001). CONCLUSION: In our cohort of patients strong association was noted
      between low SES and advanced disease, delay in diagnosis, limited access to MET
      and inferior DFS and OS. The outcome of these patients may be improved by patient
      education and availability of better health care facilities.

PMID- 15518366
TI  - Efficacy of concomitant use of PUVA and methotrexate in disease clearance time in
      plaque type psoriasis.
AB  - OBJECTIVE: To document the efficacy of concomitant use of PUVA and methotrexate
      in disease clearance time in plaque type psoriasis. METHOD: Sixty male patients
      between 18 to 50 years of age suffering from plaque type of psoriasis with PASI
      score more than 10 were enrolled in the study between March 2001 to November
      2001. They were divided into three groups of 20 patients each. Group A received
      only PUVA, Group B received only Methotrexate and group C received both PUVA and
      Methotrexate concomitantly. PUVA was given four times a week according to11011
      schedule. The end point for clearance of psoriasis was taken as 75% reduction in
      PASI score from the baseline. RESULTS: Group A: The minimum number of PUVA
      sessions needed for clearance was 20 and the maximum number was 25 (mean - 22.5).
      The mean clearance time was 5.5 weeks. The cumulative dose of UVA radiation
      ranged from 150-250 J/cm2 (mean -200 J/cm2). Group B: The time required for
      clearance was 7 weeks at the minimum and 9 weeks at the maximum (mean - 8 weeks).
      Group C: The minimum number of PUVA sessions needed for clearance was 8 and
      maximum was 12 (mean 10). The mean time for clearance was 2.5 weeks. The
      cumulative dose of UVA radiation ranged from 56-108 J/cm2 (mean-82 J/cm2). No
      significant side effects were seen in the three treatment groups. CONCLUSION: The
      results suggest that combination of PUVA and methotrexate is an effective and
      safe modality for clearance of psoriasis.

PMID- 15518367
TI  - Posters as a tool for disseminating health related information in a developing
      country: a pilot experience.
AB  - OBJECTIVE: To investigate the effectiveness of posters as a tool, for imparting
      information related to high blood pressure. METHODS: The intervention involved
      hanging posters conveying information about blood pressure, in the waiting rooms
      of 339 health facilities. The impact of this intervention was assessed after 30
      days of hanging the posters with the main assessment component of the survey
      aimed at the target audience at the facilities. 1017 people attending the
      facilities were interviewed. RESULTS: Mean age of this population was 40.4 (SD
      11.06) years. There were 79% males and 21% females. 80.2% (n=816) of the
      respondents had noticed the posters. 84.5% of the people were of the opinion that
      the poster was good. 63.7% of the people understood the overall message of the
      poster correctly. Regarding change in behaviour, 96.7% (n=789) of the people
      thought that the poster was asking them to do something; 85.9% (n=501) of these
      got their blood pressure checked compared to 60.9% (n=14) of those who did not
      think the poster was asking them to do anything (p=0.004). Of those who said that
      the poster was asking them to do something, there were varied responses as to
      what they thought the poster was asking them to do. If the response was that they
      should have their blood pressure checked, it was taken as a correct response.
      87.3% of those who said that the poster was asking them to get their blood
      pressure checked, actually got their blood pressure checked compared to 83.7% of
      those who did not understand this message (p=0.241). CONCLUSIONS: Given the
      limitations of the study it is difficult to assess the effectiveness of the
      poster in changing people's behaviour regarding blood pressure check up. This
      experience will serve as a pilot for a larger prospective study to assess poster
      as a tool for prompting people to get their blood pressure checked.

PMID- 15518368
TI  - Prevalence and factors associated with practice of modern contraceptive methods
      among currently married women in District Naushahro Feroze.
AB  - OBJECTIVE: To estimate the prevalence and factors associated with practice of
      modern contraceptive methods among currently married women of reproductive age
      group (15-49 years) in District Naushahro Feroze. METHODS: A community based
      cross-sectional survey was conducted from May to June 2000. We interviewed 420
      currently married women of reproductive age group (15-49) years. Information
      regarding socio-demographic factors, economic condition, their source of
      information for the message of family planning and reason of using any modern
      contraceptive method. RESULTS: The prevalence of modern contraceptive method was
      27.9%. Final multiple logistic regression analysis showed that with husband
      agreement (OR, 5.4; 95% CI 2.2-13.2), women could go alone to a health care
      provider (OR, 1.4; 95% CI 1.1-2.4) and women employment status (OR, 2.5 95% CI
      1.2-5.2) were significantly associated with practice of modern contraceptive
      methods. Similarly, those women who had 3 or more children were more likely to
      use any modern contraceptive methods compared to those who have 2 or less
      children. In addition, husband's education was also found significantly
      associated with family planning practice. CONCLUSION: The practice of modern
      contraceptive method is low. Socio demographic factors of women were
      significantly associated with use of modern contraceptive methods. Male and
      female education and small group discussions of various issues related to family
      planningand reproductive health may be helpful in creating awareness in the
      district.

PMID- 15518369
TI  - In-vitro activity of nitrofurantoin in enterococcus urinary tract infection.
AB  - OBJECTIVE: To compare in-vitro antimicrobial susceptibility of nitrofurantoin
      against commonly used antimicrobials for the treatment of urinary tract infection
      caused by enterococci. METHODS: A total of 144 enterococci (Enterococcus
      faecalis, n=130, Enterococcus faecium, n=14) isolated and confirmed by
      biochemical tests at the department of Microbiology, Armed Forces Institute of
      Pathology, Rawalpindi, for a period of three years were included in the study.
      The antimicrobial susceptibility tests of isolated organisms were performed by
      standard disc diffusion method as recommended by NCCLS. In addition to
      nitrofurantoin (NIT), doxycycline (DOX), co-trimoxazole (COT), ampicillin (AMP),
      imipenem (IPM) and vancomycin (VAN) were used for antimicrobial susceptibility
      testing. RESULTS: One hundred and twenty seven (88%) isolates of Enterococci were
      susceptible to NIT while 72% (n = 103) to AMP, 13% to COT, 11% to DOX, 91% to IPM
      and 99% to VAN. Among the strains resistant to AMP, COT, DOX, IPM and VAN, 50-88%
      were susceptible to NIT. CONCLUSION: Nitrofurantoin is an effective antimicrobial
      in vitro and can be used for treatment of Enterococcus urinary tract infections.

PMID- 15518370
TI  - Multi-drug resistant tuberculosis in Northern Pakistan.
AB  - OBJECTIVE: To determine the resistance pattern of Mycobacterium tuberculosis
      isolates in Rawalpindi-Islamabad. METHODS: The study was carried out at the
      Department of Microbiology, Armed Forces Institute of Pathology, Rawalpindi
      between September 2000 and August 2002. We examined 1359 pulmonary and extra
      pulmonary specimens from suspected cases of tuberculosis. The radiometric Bactec
      460 TB system was used for culture and antimicrobial susceptibility testing.
      RESULTS: Mycobacterium tuberculosis was isolated from 325 clinical specimens.
      Antimicrobial susceptibility of the isolates was tested against the four first
      line anti-tuberculous drugs (rifampicin, isoniazid, streptomycin and ethambutol).
      Fifteen percent of the isolates were resistant to a single drug, 28% were multi
      drug resistant including 7% which were resistant to all the four drugs. The
      overall resistance against individual drugs was rifampicin 32%, isoniazid 37%,
      streptomycin 19% and ethambutol 17%. CONCLUSIONS: The increasing level of drug
      resistance among mycobacterial isolates in our population is most alarming.
      Strict implementation of control measures is required to combat this unfolding
      crisis.

PMID- 15518371
TI  - Impact of antibiotic usage on resistance in microorganisms; urinary tract
      infections with E-coli as a case in point.
AB  - OBJECTIVES: In this study, we sought to establish a correlation between
      consumption of flouoroquinolones in our hospital and the emergence of ofloxacin
      resistant strains of E. coli in the urinary specimens. Data of all urinary
      samples, received at Aga Khan University Hospital between January 1995 and
      December 2002, was retrieved and analyzed. Specimens yielding E-coli as an
      isolate were included in this study. METHODS: E. coli Isolates showing >103
      colonies were identified using standard microbiological techniques. Antibiotic
      susceptibility of E. coli was tested using Kirby Bauer disc diffusion method.
      Antimicrobial usage data, obtained through hospital Pharmacy as unit utilized per
      year for Quinolones in different medical and surgical units was available only
      for the period of 1997- 2002. RESULTS: Among 32,722 urinary specimens E. coli
      (53%) was the most frequent isolate. Steady increase in the number of ofloxacin
      resistant E. coli was noted, 24% in 1995 to 55% in 2002. Maximum quinolone
      resistant E. coli have been observed in Medical units, 41% in 1997 increasing to
      70% in 2002, followed by Surgery units (35% to 54%) and Pediatrics (12 to 38%).
      Sharp increase in ofloxacin consumption in our hospital, 1997 (28613 units) to
      2002 (96880 units) has been observed. Trends in quinolone resistance correlate
      significantly with utilization in the same period as shown by linear regression.
      CONCLUSION: E. coli resistance against most antibiotics has been on a rise
      particularly for quinolones. The utilization of quinolones correlates with
      increasing resistance in our hospitalized patients.

PMID- 15518372
TI  - Is there a correlation between degree of viremia and liver histology in chronic
      hepatitis C?
AB  - OBJECTIVE: To determine the correlation between degree of histological liver
      damage and serum HCV RNA level in patients of chronic hepatitis C, in order to
      evaluate the usefulness of HCV RNA estimation as an alternate to liver biopsy.
      METHODS: This non-interventional descriptive study, was carried out at the
      department of Pathology, Army Medical College, Rawalpindi, Pakistan between April
      and September 2002. Core needle liver biopsies of fifty five patients of chronic
      hepatitis C were evaluated according to Knodell's histological activity index
      system. The patients were categorized into four subgroups depending upon the
      grade and stage of disease according to Desmet's classification, and into three
      groups according to degree of viremia. RESULTS: Five patients had mild viremia,
      43 moderate and 7 had severe viremia. Seven patients had minimal disease, 9 mild,
      22 moderate and 17 had severe chronic hepatitis. Eight patients had no fibrosis,
      20 had fibrous portal expansion, 19 bridging fibrosis, and 8 patients had
      cirrhosis. No significant correlation was found between serum HCV RNA levels and
      grade or stage of the disease, with correlation coefficients of rs = -.054 and rs
      = .034 respectively. Moreover, no individual component of the HAI correlated with
      serum HCV RNA levels. CONCLUSION: Serum HCV RNA level does not determine the
      degree of hepatic injury precisely and liver biopsy is necessary to accurately
      evaluate the extent of liver damage.

PMID- 15518373
TI  - Wilson's disease: a review.

PMID- 15518374
TI  - Fatal endocarditis due to Aspergillus flavus in Iran.

PMID- 15518375
TI  - Sexual and reproductive health promotion at the grassroots; theater for
      development--a case study.

PMID- 15518376
TI  - Localization of upper GI bleed on delayed imaging with 99mTc tagged RBC
      angiogram.

PMID- 15518377
TI  - Cardiovascular health--behaviour of medical students in Karachi.
AB  - OBJECTIVE: To assess the health behaviour and perceptions of medical students
      towards cardiovascular disease. METHODS: This descriptive cross-sectional survey
      was conducted on 203 Pakistani medical students enrolled in a private medical
      college in Karachi, Pakistan using systematic random sampling. It was based on a
      self-administered questionnaire. RESULTS: Eight percent smoked, 9% were
      overweight, 33% had a family history of coronary artery disease, 32% regulated
      dietary fat intake, 28% exercised regularly, 62.1% knew personal blood pressure
      and 5.4% personal cholesterol levels. Regarding developing cardiovascular disease
      in the future, 62% showed concern but only 54% of these adopted preventive
      practices. About 46% believed medical college life had a harmful effect on their
      health. Gender, family history and personal health status perception were
      behavior modifying influences (p<0.05). Reasons reported for their behavior were:
      no need of prevention at their age (38.3%) and never thinking about these issues
      (37.0%). CONCLUSIONS: The study shows a high prevalence of coronary artery
      disease family history, inappropriate dietary intake, physical inactivity; poor
      screening practices and lack of awareness. The results underscore the urgent need
      to promote preventive knowledge and practices among medical students, if they are
      to become prevention oriented physicians and counsel patients on preventive
      strategies to counter the rapidly increasing burden of cardiovascular diseases
      effectively.

PMID- 15518378
TI  - Immunity in medicine.

PMID- 15518379
TI  - Professionals need more understanding of club drugs.

PMID- 15518380
TI  - The road to service excellence: quality system implementation in health and human
      services.

PMID- 15518381
TI  - Facilities' smoking dilemma: clamp down or lighten up? Centers address positives,
      perils of smoking bans.

PMID- 15518382
TI  - Bringing integrated treatment for co-occurring disorders to life.

PMID- 15518383
TI  - Making recovery real: the critical role of treatment planning.

PMID- 15518384
TI  - Picking up where facilities leave off: MCO closes gap between facility treatment,
      discharge aftercare.

PMID- 15518385
TI  - Independent medical review, patient protection, and behavioral healthcare.

PMID- 15518386
TI  - Electrochemical scanning tunneling microscope imaging of self-assembled monolayer
      of double-stranded DNA on Au(111).
AB  - Self-assembled monolayer of a double-stranded DNA, which was formed by a 20-nt 5'
      thiol-modified oligonucleotide at the interface of Au(111)/solution, has been
      imaged and studied with electrochemical scanning tunneling microscopy (ECSTM).
      The results showed that the preferred directions of the adsorbed DNA were <110>
      and <112>. The measured width of the DNA stripes was 0.95 +/- 0.02 nm, which was
      consistent with the width of dsDNA base pairs. The contour of DNA in the STM
      image consisted of a series of blobs, which were due to the anchoring of the
      bases to the substrate along the dsDNA chain. The imaging of a large-scale array
      of DNA lying flat on the substrate offers a convenient method for the further
      application of high-resolution STM to the study of the interaction between DNA
      and a variety of molecules.

PMID- 15518387
TI  - Photocatalytic activity of gold nanocrystals and its role in determining the
      stability of surface thiol monolayers.
AB  - Colloidal gold nanocrystals were found to be efficient photocatalysts for the
      oxidation of thiols to the corresponding disulfide in aqueous solution under UV
      radiation, although no noticeable catalytic effect of gold nanocrystals was
      observed under dark conditions for the same process. The turnover number per
      particle increased with the size of the nanocrystals and reached 1200 molecules/s
      for 45-nm gold nanocrystals. The photochemical instability of colloidal gold
      nanocrystals coated by thiol ligands was found to be determined by the
      photocatalytic oxidation of the thiol ligands.

PMID- 15518388
TI  - A new class of far-red and near-infrared biological labels based on alloyed
      semiconductor quantum dots.
AB  - Ternary cadmium selenium telluride quantum dots (CdSe(1-x)Tex, x = mole fraction
      of tellurium) have been prepared for potential use as constant-size biolabels
      with tunable fluorescence emission in the far-red and near-infrared (650-850 nm)
      spectral range. In contrast to particle size tuning reported for binary dots, we
      show that molar composition can be used to tune the optical and electronic
      properties of alloyed semiconductor nanocrystals without changing the particle
      size. A surprising finding is a nonlinear relationship between the composition
      and the absorption/emission energies, leading to new properties not obtainable
      from the parent CdSe and CdTe binary systems. Coating the alloy cores with a
      higher band-gap material such as CdS improves the fluorescence efficiencies to
      about 40-60% at room temperature and allows the preparation of water-soluble and
      biocompatible alloyed dots at similar quantum yields. A cadmium-rich surface is
      found to improve mercapto ligand binding and the long-term stability of water
      soluble dots.

PMID- 15518389
TI  - Integration of an immunoassay system into a microchip for high-throughput assay.
AB  - An immunosorbent assay system was integrated into a glass microchip. The scale
      merits of liquid microspace for molecular behavior contributed remarkably to
      reduced assay time, and troublesome operations required for conventional
      immunosorbent assays could be replaced by simple operations. Moreover, a micro
      immunoassay system suitable for simultaneous assay of multiple samples was
      constructed on a microchip. The chip had branching multichannels and four
      reaction and detection regions; thus the constructed system could process four
      samples at a time with only one pump unit. A higher throughput assay was realized
      with the branching structure chip.

PMID- 15518390
TI  - Covalent immobilization of DNA onto functionalized mica for atomic force
      microscopy.
AB  - The immobilization of DNA on the self-assembled monolayer of 3
      aminopropyltrimethoxysilane (APTES) on mica wafer functionalized with
      glutaraldehyde (GA) by chemical bonding was studied by atomic force microscopy
      (AFM). The DNA used for our investigation was amplified by polymerase chain
      reaction, and primers were labeled with a -NH2 group at their 5' terminus. The
      surfaces were analyzed by X-ray photoelectron spectroscopy (XPS) and AFM. Results
      from XPS and AFM showed that the mica with the APTES and activated with GA can be
      formed, and the flatness of the mica can be adapted for AFM images. We found that
      the modified surface was capable of binding DNA molecules so that it withstood a
      thorough rinsing with a solution of sodium dodecylsulfate. Covalent binding
      between the aldehyde-terminated membrane and -NH2 groups at both ends of double
      stranded DNA resulted in immobilization and straightening of the DNA.

PMID- 15518391
TI  - A novel fluorescent label based on organic dye-doped silica nanoparticles for
      HepG liver cancer cell recognition.
AB  - In this paper, we report a method for the recognition of HepG liver cancer cells
      with the use of a novel fluorescent label based on organic dye-doped fluorescent
      silica nanoparticles. The novel organic dye-doped silica nanoparticles are
      prepared with a water-in-oil microemulsion technique. The silica network is
      produced by the controlled synchronous hydrolysis of tetraethoxysilane and 3
      amino-propyltriethoxysilane (APTES). The organic dye fluorescein isothiocyanate
      is doped inside as a luminescent signaling element, through covalent bonding to
      the amino group of APTES. The organic dye-doped core-shell nanoparticles are
      highly luminescent and exhibit minimal dye leaching and excellent photostability.
      A novel fluorescent label method based on biological fluorescent nanoparticles
      has been developed. The dye-doped fluorescent silica nanoparticles are covalently
      immobilized with anti-human liver cancer monoclonal antibody HAb18. We have used
      antibody-labeled fluorescent nanoparticles to recognize HepG liver cancer cells.
      It has been observed that the bioassay based on the organic dye-doped
      nanoparticles can identify the target cells selectively and efficiently. The
      fluorescent nanoparticle label also exhibits high photostability.

PMID- 15518392
TI  - Luminescent nanoparticle probes for bioimaging.
AB  - Bioimaging with luminescent nanoparticle probes have recently attracted
      widespread interest in biology and medicine. In comparison with commonly used
      organic dyes, luminescent nanoparticles are better in terms of photostability and
      sensitivity. These optical features of nanoparticle probes are critical for real
      time tracking and monitoring of biological events in the cellular level, which
      may not be accomplished using regular fluorescent dyes. Nanoparticle probes are
      also shown highly suitable for immunoassay and other diagnostic and therapeutic
      applications. In this article, we describe a variety of optical nanoparticle
      probes such as quantum dots, metal nanoparticles, dye-doped nanoparticles etc.
      for bioimaging applications.

PMID- 15518393
TI  - Protein immobilization on carbon nanotubes through a molecular adapter.
AB  - A new approach to the modification of carbon nanotubes with biomolecules for the
      development of nanoscale biosensors is presented. Alkaline phosphatase was
      immobilized on the surface of multi-wall carbon nanotubes utilizing a layer-by
      layer methodology. Carbon nanotubes were incubated with streptavidin, resulting
      in the formation of a protein layer on the surface of the nanotubes. Biotinylated
      alkaline phosphatase was then allowed to bind to streptavidin, anchoring the
      sensing protein onto the surface. Electrochemical biosensors were constructed by
      using carbon nanotubes compacted into pellets. 1-Naphthyl phosphate, which is
      hydrolyzed by alkaline phosphatase to the electroactive 1-naphthol, was used as a
      substrate. Electrodes constructed in this manner were observed to generate an
      electrochemical signal that was a function of substrate concentration.

PMID- 15518394
TI  - Template synthesis of gold nanotubes in an anodic alumina membrane.
AB  - Nanotube-containing membranes prepared by the template method show promise for
      use as highly selective filters for membrane-based chemical and biological
      separations. Most of the work to date has been done on gold nanotubes prepared by
      electroless deposition of Au within the pores of polymeric filtration membranes.
      These polymeric filters have very low porosities (< 1%), and, as a result, the
      flux through Au nanotube membranes based on these templates is very low. In
      contrast, the other popular template membranes-anodic aluminas-have high
      porosities-30% to 50%. In spite of this potential advantage of anodic alumina
      templates, there have been no reports of electrolessly plated Au nanotubes within
      the pores of these templates. This is because the electroless plating method used
      to deposit Au nanotubes in polymeric templates does not work in aluminas. We have
      developed a modified electroless plating strategy that can be used to deposit
      high-quality Au nanotubes within the pores of the alumina templates. We describe
      this new plating method here.

PMID- 15518395
TI  - Study of the effect of metal ion on the specific interaction between protein and
      aptamer by atomic force microscopy.
AB  - We have studied the effect of metal ions on the specific interaction between a
      protein, immunoglobulin E (IgE), and its 37-nt DNA aptamer with atomic force
      microscopy (AFM). Protein aptamers are a new class of synthetic single-stranded
      DNA/RNA oligonucleotide generated from in vitro selection to selectively bind
      with target proteins. The IgE aptamers have been developed and are expected to be
      promising reagents in IgE detection and new anti-allergic drug development. It is
      known that the presence of metal ions in the buffer usually has a strong effect
      on the affinity of single-stranded DNA for protein. In this work, the effect of
      two representative monovalent ion and divalent ion on the binding of IgE and the
      aptamer has been studied at the single-molecule level. The results from the AFM
      force measurements show that the metal ions not only reduce the single-molecular
      rupture force but also reduce the number of bonds formed between IgE and the
      aptamer.

PMID- 15518396
TI  - Single-molecule imaging of the dynamic interactions between macromolecules.
AB  - In recent years, the development of single-molecule detection techniques has
      allowed the dynamic properties of biomolecules, which are normally obscured in
      conventional ensemble measurements, to be measured. One of these single-molecule
      detection techniques allows the measurement of dissociation and association
      events of individual molecules to be measured. This technique is based on the
      unique premise that the mobility between molecules that are bound and the
      mobility between those that are free in solution are different. The binding of
      ATP at the beginning and its dissociation at the end of the hydrolysis reaction
      were detected at the single-molecule level in real time. In this study, we
      extended this technique to image the dynamic interactions between large
      biomolecules (protein/protein and protein/polysaccharide). The binding and
      dissociation of fluorescently labeled macromolecules to partner molecules fixed
      on a glass surface were visualized by total internal reflection fluorescence
      microscopy. The dynamic interactions between the proteins in two energy
      conversion systems, that is, signaling proteins and enzyme molecules moving on
      dextran, have been measured. In these systems, the dynamic interactions were
      sensitive to the factors determining the chemical reactions. Thus, the dynamic
      interactions monitored in the single-molecule measurements provided useful
      information to further the understanding of the underlying mechanisms of energy
      conversion systems.

PMID- 15518397
TI  - Plasmon absorption of gold nanoparticles in linear polymer solutions.
AB  - Gold nanoparticles (GNPs) are stable in a number of linear polymer solutions,
      including poly(vinyl alcohol), poly(N-vinyl-2-pyrrolidone), hydroxyethyl
      cellulose, and poly(ethylene oxide) (PEO). Of these, PEO, with a wide range of
      molecular mass (from 0.3 to 8 MDa), is particularly attractive for exploring the
      interaction between the GNPs and polymer molecules. We have found that the colors
      of the GNPs are significantly different in PEO solutions at concentrations below
      and above entanglement threshold concentration (Phi*), which allows one to
      determine Phi* values for different sizes of PEO from the inflection points of
      the plots of the absorbance at 600 nm against the concentration of PEO. The Phi*
      values are close to those obtained by the viscosity measurements, showing the
      usefulness of this simple method. Transmission electron microscopy images have
      confirmed that the change in the absorbance is due to the aggregation and/or
      agglomeration of the GNPs in PEO solutions.

PMID- 15518398
TI  - Polyelectrolyte-mediated assembly of copper-phthalocyanine tetrasulfonate
      multilayers and the subsequent production of nanoparticulate copper oxide thin
      films.
AB  - An approach to producing films of nanometer-sized copper oxide particulates,
      based on polyelectrolyte-mediated assembly of the precursor,
      copper(II)phthalocyanine tetrasulfonate (CPTS), is described. Multilayered CPTS
      and polydiallyldimethylammonium chloride (PDADMAC) were alternately assembled on
      different planar substrates via the layer-by-layer (LbL) procedure. The growth of
      CPTS multilayers was monitored by UV-visible spectrometry and quartz crystal
      microbalance (QCM) measurements. Both the UV-visible spectra and the QCM data
      showed that a fixed amount of CPTS could be attached to the substrate surface for
      a given adsorption cycle. Cyclic voltammograms at the CPTS/PDADMAC-covered gold
      electrode exhibited a decrease in peak currents with the layer number, indicating
      that the permeability of CPTS multilayers on the electrodes had diminished. When
      these CPTS multilayered films were calcined at elevated temperatures, uniform
      thin films composed of nanoparticulate copper oxide could be produced.
      Ellipsometry showed that the thickness of copper oxide nanoparticulate films
      could be precisely tailored by varying the thickness of CPTS multilayer films.
      The morphology and roughness of CPTS multilayer and copper oxide thin films were
      characterized by atomic force microscopy. X-ray diffraction (XRD) measurements
      indicated that these thin films contained both CuO and Cu2O nanoparticles. The
      preparation of such copper oxide thin films with the use of metal complex
      precursors represents a new route for the synthesis of inorganic oxide films with
      a controlled thickness.

PMID- 15518399
TI  - Assembly of silica nanoparticles for two-dimensional nanomaterials.
AB  - To realize the great potential of nanoparticles as new materials for biomedical
      applications, the nanoparticles will have to be assembled in such a way that the
      newly created assembly will have unique properties that conventional materials do
      not possess. This will enable nanomaterials to be used for many novel
      applications. We have attempted to assemble silica nanoparticles to create a two
      dimensional nanomaterial, which might be useful for biosensor and biochip
      production. The silica nanoparticles are synthesized and assembled in a monolayer
      fashion through the use of halogenated silanes. Photolithography techniques are
      used to pattern the glass surface prior to nanoparticle attachment. The
      concentration of the silica nanoparticles in the solution controls the surface
      coverage of nanoparticles on the glass surface. Different patterned silica arrays
      can be made with controlled surface coverage. The nanoparticle-covered surface is
      successfully tested for surface-enhanced enzymatic reactivity for the detection
      of a neurotransmitter, glutamate. This report demonstrates the feasibility of
      assembling nanoparticles for biosensor development.

PMID- 15518400
TI  - Methods for labeling quantum dots to biomolecules.
AB  - Semiconductor quantum dots (QDs) are thought to be the most promising fluorescent
      probe for biological and biomedical applications because of their unique size
      dependent optical and electronic properties. QD bioconjugates provide important
      advantages over conventional organic dyes. This review compares the optical
      properties of nanoparticles and dyes and describes the surface modification of
      the QDs and the methods for biomolecules conjugating to QDs. In addition, the
      effect of QDs on normal physiology in real biological applications is discussed.

PMID- 15518401
TI  - IBVA President warns of dangers of complacency on animal health.

PMID- 15518402
TI  - Support for new graduates: tackling the issue from both ends.

PMID- 15518403
TI  - Maintaining momentum on animal health and welfare.

PMID- 15518404
TI  - Errors associated with milk cell counting.
AB  - The accuracy of somatic cell counts in milk samples was investigated in four
      studies. First, the counts recorded by one milk buyer in one supply over six
      months ranged from 105,000 to 401,000 cells/ml with no apparent changes in the
      volume of milk consigned or the level of mastitis in the herd that would explain
      this wide range. Secondly, the counts in daily samples from one bulk milk supply
      for 28 days ranged from 84,000 to 282,000 cells/ml, again with no apparent
      changes in the performance of the herd to explain the wide range. Thirdly, the
      replicated counts recorded for one sample by three separate laboratories agreed
      closely; however, when a sample with a high cell count was interspersed then two
      of the three laboratories reported high cell counts suggestive of 'carry-over' in
      excess of the 2 per cent 'allowable' Finally, cell count data from three separate
      laboratories on samples from 21 cows for 33 days revealed problems with the
      misidentification of samples on the farm in 1 per cent of the samples, and
      misidentification and mishandling of 1 to 2.6 per cent of the samples in the
      laboratories. All three laboratories differentiated samples from cows with
      subclinical and clinical mastitis, but the mean cell count of the uninfected cows
      varied between the laboratories with one of them recording statistically
      significantly higher counts over the period.

PMID- 15518405
TI  - Ultrasonographic evaluation of partially attenuated congenital extrahepatic
      portosystemic shunts in 14 dogs.
AB  - Doppler ultrasonography was used to evaluate the portal vein in 14 dogs before,
      immediately after and four weeks after a partial ligation of a congenital
      extrahepatic portocaval shunt. By four weeks after the operation, the hepatofugal
      or zero flow in the portal vein segment cranial to the shunt origin had become a
      hepatopetal flow in 13 of the dogs, which became clinically healthy. The other
      dog continued to have a hepatofugal flow in the portal vein cranial to the origin
      of the shunt and continued to show clinical signs of hepatic encephalopathy. The
      shunt remained functional in six of the dogs, and three of them developed
      portosystemic collaterals in addition. In the other eight dogs the patent shunt
      was non-functional, because a hepatopetal flow was detected in the shunt adjacent
      to the portal vein. This flow was the result of the splenic vein entering the
      shunt, and the splenic blood dividing; some flowed via the shunt towards the
      portal vein, preventing the portal blood from shunting, and the rest flowed via
      the attenuated shunt segment to the caudal vena cava. Shunting of the splenic
      venous blood was clinically insignificant.

PMID- 15518406
TI  - Listeria monocytogenes in horses in Iceland.
AB  - Twenty isolates of Listeria monocytogenes associated with five confirmed and four
      suspected incidents of listeriosis in horses in Iceland were characterised by
      serotyping, pulsed-field gel electrophoresis and ribotyping. Semiquantitative
      estimates of the numbers of L monocytogenes were made on faeces from horses with
      clinical signs of listeriosis and on grass silage fed to them. Large numbers of L
      monocytogenes were often found in the faeces of horses with severe signs of
      disease. The 20 isolates could be divided into six genotypes, each incident
      involving only one genotype. One serovar 1/2a genotype was associated with three
      confirmed incidents of listeriosis in 1991, 1993 and 1997. In one incident, the
      same genotype was isolated from the organs of a horse with listeriosis and from
      the spoiled grass silage fed to it.

PMID- 15518407
TI  - Possible introduction of bluetongue into the Balearic Islands, Spain, in 2000,
      via air streams.

PMID- 15518408
TI  - Large granular lymphoma in a mule.

PMID- 15518409
TI  - Malignant catarrhal fever in a Barbary sheep (Ammotragus lervia).

PMID- 15518410
TI  - Variable tuition fees.

PMID- 15518411
TI  - Early neutering of cats.

PMID- 15518412
TI  - Selecting for scrapie-resistant sheep.

PMID- 15518413
TI  - Badgers and bovine TB.

PMID- 15518414
TI  - Badgers and bovine TB.

PMID- 15518415
TI  - The Hobday Family.

PMID- 15518416
TI  - [Thyroid and cardiovascular disorders].
AB  - In this study three problems concerning interactions between thyroid and
      cardiovascular system are discussed. Cardiac arrhythmias, congestive heart
      failure, pleural effusion, hyperlipidaemia, arterial hypertension may be
      consequences of thyroid disorders leading to inappropriate hormone secretion.
      During such illnesses as heart failure, myocardial infarction and in patients
      undergoing coronary artery bypass surgery profound changes may occur in thyroid
      hormone metabolism known as sick euthyroid syndrome. Treatment with amiodarone
      may lead to changes in thyroid tests results and to development of hypothyroidism
      or thyrotoxicosis.

PMID- 15518417
TI  - [Specific and nonspecific fetal cardiac problems].
AB  - Data base of our Department for Diagnosis & Prophylaxis of Congenital
      Malformations Research Institute Polish Mother's Memorial Hospital was analyzed
      for 1994-2001, including 7047 fetal echocardiographic examinations in 5196
      fetuses. In 1861 pregnant women at least one congenital malformation was
      diagnosed. There were 68% of low risk pregnancies and 32% of high risk
      pregnancies. The majority of fetal malformations were central nervous system
      malformations (25%) and congenital heart defects (23%). Fetal cardiac anomalies
      were analyzed both in singleton and multiple pregnancies. The most common fetal
      cardiac anomalies similar to postnatal life were congenital heart defects (8%),
      tricuspid valve regurgitation in normal heart anatomy (6%) and fetal arrhythmias
      (6%). The most common cardiac anomalies specific for fetal life were cardiac
      anomalies due to non-immunological hydrops fetalis (4.2%) and functional
      tricuspid valve regurgitation due to maternal pharmacotherapy or fetal infection
      (3.2%), other rare anomalies were: ectopia cordis, relative cardiomegaly and
      premature ductus arteriosus closure. There were also other sporadic specific for
      fetal life cardiac anomalies. The most common cardiac anomalies in twin
      pregnancies was twin to twin transfusion syndrome (10%), the other are cardiac
      problems in conjoined twins.

PMID- 15518418
TI  - [Left ventricular mass and function in hypertensive and obese children and
      adolescents with family history of cardiovascular diseases].
AB  - The aim of the study was to answer the question if there are any abnormalities in
      the function of left heart ventricle and in its mass in children and adolescents
      with hypertension and obesity and positive family history of cardiovascular
      diseases. MATERIAL AND METHODS: The study group consisted of 70 children and
      adolescents aged 11-19 yrs. They were divided into: group A--patients with
      hypertension (n=17) group B--patients with hypertension and positive family
      history of hypertension (n=16), group C--patients with hypertension, obesity and
      positive family history of hypertension (n=19). Control group consisted of 18
      healthy children. Left ventricle heart mass and systolic-diastolic function were
      assessed with use of ultrasonographic method on Hewlett Packard Sonos 4500.
      RESULTS: In 35 (50%) of the studied patients we confirmed hypertension in the
      family. In children with hypertension and positive family history we found
      statistically higher left ventricle mass (p<0.05), higher ratio E/A (p<0.001),
      shorter deceleration time of wave E (p<0.05) in comparison to control group. In
      the group of children with hypertension, positive family history and additionally
      obesity we found longer isovolumetric relaxation time (IVRT) (p<0.05) and EF
      (p<0.05) in comparison to control group. CONCLUSIONS: 1. Children and adolescents
      with hypertension and positive family history of hypertension revealed to have
      higher left ventricle heart mass and diminished parameters of systolic-diastolic
      function of left ventricle. 2. Normotensive children of hypertensive parents and
      children with hypertension should be taken into particular medical health care by
      pediatricians or general practitioners.

PMID- 15518419
TI  - [Estimation of autonomic nervous system tension in patients with syncope of
      unknown origin--traps in clinical interpretation results of heart rate
      variability].
AB  - Voluntary character of a choice of statistical methods weakens the reliability of
      the results of heart rate variability assessment and based on them clinical
      conclusions. The aim of the study was to estimate reliability of the chosen
      statistical methods of analysing changes in spectral components during tilt
      testing (TT). MATERIAL AND METHODS: 62 patients (34 women), the average age 38.8
      +/- 12.8 years, with at least 2 syncopes during the last 6 months that had not
      been diagnosed by other examinations, were enrolled. The control group consisted
      of 44 age- and sex-matched volunteers (21 women), the average age 37.4 +/- 12.6
      years, who had no history of syncope. All subjects underwent tilt testing
      according to Westminster protocol. If the result of a passive phase was negative,
      0.25 mg nitroglycerine was applied sublingually and the examination was continued
      for the next 20 minutes. The type of syncopal reaction was defined according to
      VASIS classification (the vasovagal syncope international study). The evaluation
      of heart rate variability was based on the frequency domain methods. The low
      frequency (LF), the high frequency (HF) component and the balance (the LF/HF
      ratio) were estimated. The response of the autonomic nervous system (AUN) to
      tilting was evaluated by tests comparing mean values of respective components
      (the quantitative analysis) and by the modulation index (deltaXFm) reflecting, in
      percentage terms, changes in analyzed variable values. Taking into account the
      obtained results there was also a qualitative analysis performed. This analysis
      referred to the modulation index, which reflected increase or decrease in
      spectral component value. RESULTS: Tilt testing explained vasovagal origin of
      syncope in 35 (60%) patients with syncope. Patients were divided into 3 groups
      according to anamnesis data and results of tilt testing. Group I consisted of 42
      healthy volunteers who had negative result of TT Group II--35 patients with
      history of syncopes and positive result of TT, and Group III--23 patients with
      history of syncopes and negative result of TT. In all study groups the
      quantitative analysis revealed the decrease in the LF and HF component values,
      whereas the evaluation of autonomic nervous system reactivity based on deltaXFm
      showed the increase in LF power, concomitant with strongly marked, nearly uniform
      decrease in HF power in Group I and II. The results obtained from the qualitative
      analysis did not reveal statistically significant differences between study
      groups in distribution of defined types of autonomic nervous system reactions.
      CONCLUSIONS: 1. The quantitative analysis has limited credibility in clinical
      interpretation of changes in autonomic nervous system activity (especially in the
      low frequency component--LF) occurring during tilt testing. 2. The best
      estimation of autonomic nervous system activity during tilt testing is assured by
      the modulation index supplemented by the preliminary selection of data, i.e.,
      rejection of extreme values or those rarely occurring qualitative changes in
      spectral components.

PMID- 15518420
TI  - [Formation of the selected biochemical markers in the patients with
      atherosclerotic arterial obliteration and the coexistent infection with Chlamydia
      psittaci].
AB  - In the arterial wall which is atheromatously changed both basic EB and reticular
      RB bodies of Chlamydia bacteria may be present. The role of these micro-organisms
      in the pathogenesis of arteriosclerosis is not thoroughly recognized yet. It is
      unknown whether Chlamydia initiate or lead to the inflammation of the already
      existent disease process. That is why it is expedient to carry out the research
      determining the correlation between the presence of Chlamydia bacteria in the
      operated arteries and the formation of the selected biochemical indicators.
      During the operation the imprint specimen was taken from the arterial wall, which
      was subsequently painted using stamp's method. EB bodies were marked in the
      immunofluorescence test with the usage of specific antibodies. The concentration
      of C-reactive protein was marked with the help of the rocket
      immunoelectrophoresis. The examination of blood lipids and fibrinogens was
      conducted with the usage of a colorimetric method with the help of ready-made
      kits. On the basis of the obtained data two groups of patients were
      distinguished. The first group comprised 16 patients (26%); here elementary EB
      bodies were detected both in the imprint specimens and the blood serum. In all
      the patients assigned to the first group the presence of anti-Chlamydia
      antibodies in the blood serum was observed. The second group consisted of the
      remaining 47 patients (74%); here no currently lasting Chlamydia infection was
      stated. On the basis of the conducted research and statistic calculations it is
      justified to point the correlation between the concentration of C-reactive
      protein and HDL cholesterol in the group of patients with the detected Chlamydia
      bacteria in comparison to the group of patients with no infection. However no
      statistically significant relationship between the concentration of fibrinogen,
      total cholesterol, LDL cholesterol and triglycerides was observed in the relation
      to the analyzed groups.

PMID- 15518421
TI  - [Is obesity associated with a polymorphism Pro12Ala and Pro115Gln in PPARgamma
      gene?].
AB  - Gene PPARgamma is one of the pivotal factors that influence adipocyte
      differentiation. It is transcriptional factor that plays a crucial role in the
      regulation of genes involved in lipid utilisation and storage as well as insulin
      action. The aim of this study was to evaluate whether PPARgamma Pro12Ala and
      Pro115Gln polymorphisms are connected with obesity and its anthropological
      parameters. MATERIAL AND METHODS: we investigated 93 subjects: 72 women (37 non
      obese and 35 obese) and 21 men (8 non-obese and 13 obese). We performed
      anthropological examination: BMI, WHR and total-body densitometry in the whole
      group. PPARg polymorphism was studied using PCR and RFLP. RESULTS: Pro12Pro
      ("wild" type) variant was present in 57 subjects (32 obese and 25 non-obese): 45
      women (26 obese and 19 non-obese) and 12 men (6 obese and 6 non-obese).
      Heterozygosity Pro12Ala was observed in 20 subjects (8 obese and 12 controls): 15
      women (4 obese and 11 lean) and 5 men (4 obese). Homozygosity Ala12Ala was
      discovered in 16 subjects (8 obese and 8 controls): 12 women (5 obese and 7 non
      obese) and 4 men (3 obese). Pro115Gln variant was not found in any of the studied
      subjects. CONCLUSIONS: The frequency Ala allele (pro12Ala and Ala12Ala variant)
      was 28% in the whole group and 25% in the obese subjects. However the Pro12Ala
      polymorphism is quite common, it does not seem to be directly connected with
      onset of obesity. But it is interesting that the Ala allele is more frequent in
      non-obese women comparing to obese women (33 vs 20%). Reverse tendency was seen
      in men. Pro12Ala and/or Ala12Ala polymorphism is twice more frequent in obese
      subjects comparing to non-obese ones (38 vs 19%).

PMID- 15518422
TI  - [Evaluation of the vascular endothelial growth factor in children and adolescents
      with type 1 diabetes].
AB  - Diabetes type 1 is the chronic disease, leading to many acute and late
      complications. Pathogenesis of the late complications is not fully understood.
      Lately, growth factors, and especially vascular endothelial growth factor (VEGF)
      are gaining great interest as potential risk factors of late diabetic
      complications, mainly nephropathy and retinopathy The aim of the study was
      evaluation of the level of VEGF in children and adolescents with diabetes type 1,
      and searching for correlation between level of this cytokine and microangiopathy
      and metabolic control. MATERIAL AND METHODS: 68 young diabetic type patients were
      studied, aged 8-20 yrs (x = 15.54 yrs), suffering from diabetes type 1 from 2.3
      16.5 yrs (x = 7.84 yrs), 34 boys, 34 girls. They were all under control of
      Outpatient Diabetic Department. Control group were healthy children, age and
      gender matched. Metabolic control was assessed on the basis of HbA1c level. All
      children underwent ophthalmology examination, microalbuminuria was evaluated in
      24 hours urine samples. VEGF was estimated with use of immunoenzymatic method (RD
      Systems). RESULTS: In the study group we found: significantly higher levels of
      VEGF compared to control group (328.68 +/- 251.6 vs 132.19 +/- 85.51 pg/ml:
      p<0.05). We did not find any differences between genders in VEGF level. VEGF
      increases with diabetes duration time, and the highest values are in children
      with diabetes duration over 10 years, although the differences did not reach
      statistical significance. VEGF level was significantly higher in children with
      poor metabolic control of the disease (406.65 +/- 322.11 pg/ml vs 132.19 +/-
      85.51 pg/ml; p<0.05). Patients with retinopathy had the highest level of VEGF,
      compared to children without complications. CONCLUSIONS: Assessment of VEGF level
      can be useful method in prognosis of diabetes microangiopathic complications. As
      microalbuminuria occurs relatively late in diabetic complications process,
      evaluation of VEGF may become a prognostic marker of the earliest phases of this
      complication.

PMID- 15518423
TI  - [Serum copper and zinc level in patients suffering from infectious mononucleosis
      and after the regression of clinical symptoms].
AB  - The aim of this work was to assess the serum copper (Cu) and zinc (Zn) level and
      ratio Cu/Zn in the acute, symptomatic period of infectious mononucleosis and
      during the convalescence period, when no clinical symptoms were present. MATERIAL
      AND METHODS: We examined 50 persons, including 26 patients (14 women and 12 men)
      in the age of 16 to 27 years, examined in the acute, symptomatic period of the
      disease. The diagnosis of infectious mononucleosis was based on the clinical,
      haematological, biochemical and serologic criteria. Cu and Zn concentration was
      measured 3 times: on the 1st day and the 2nd week of hospitalisation, and also
      after the regression of clinical symptoms. The control group consisted of 24
      healthy individuals (13 men and 11 women) in the age of 17 to 26 years. Cu and Zn
      concentration was measured once in this group. All measurements of Cu and Zn
      serum concentration were done using the method of atomic absorption
      spectrophotometry (AAS) with AAS-3 spectrophotometer of Carl Zeiss-Jena
      production, at the wavelength for Cu--324.8, Zn--213.9 nm. We observed the Cu and
      Zn serum concentration and ratio Cu/Zn in patients with acute, symptomatic
      infectious mononucleosis and also after the regression of clinical symptoms to be
      statistically higher that the results from the healthy individuals. CONCLUSION:
      The statistical significant elevated serum Cu and Zn concentration observed
      during the course of infectious mononucleosis and after clinical symptoms
      regression in comparison to healthy persons expressed the perturbation of trace
      elements homeostasis. If copper to zinc ratio reflects myeloproliferative
      diseases activity, the practical value for infectious mononucleosis monitoring is
      the same as copper and zinc serum level measurement.

PMID- 15518424
TI  - [Concentration of soluble CD4, CD8, CD25 receptors as well IFN-gamma and IL-4
      released by lymphocyte of chronic Lyme patients cultured with 3 genotypes of
      Borrelia burgdorferi].
AB  - The aim of the study was the evaluation of sCD4, sCD8, sCD25, IFN-gamma and IL-4
      released in the supernatant of lymphocyte cultures from patients with chronic
      Lyme stimulated by B. burgdorferi. Three genotypes of B. burgdorferi: sensu
      stricto B-31, B. garinii 20047 and B. afzelii--VS 46110 were used for
      stimulation. The study group consisted of 23 patients (13 males and 10 females).
      The control group (K) consisted of 10 healthy people. Peripheral blood
      mononuclear cells were incubated in atmosphere of 5% CO2 at 37 degrees C after
      the addition of spirochetes of B. afzelii (VS 46110), B. garinii (20047), B.
      burgdorferi sensu stricto (B-31) in the concentration of 10(8) spirochetes/well,
      for 5 days. The supernatants were analyzed for concentration of sCD4, sCD8, sCD25
      and IL-4, IFN-gamma by means of ELISA method. The increase in sCD4, sCD8 and
      sCD25 concentrations indicates the activation of these lymphocytes with CD4, CD8,
      CD25 receptors in this group of patients. A significantly higher concentration of
      IFN-gamma shows the long-lasting cellular response with the advantage of Th1 type
      profile cytokines. All used strains had immunogenic properties but B. afzelii had
      the strongest in patients with chronic borreliosis.

PMID- 15518425
TI  - [Analysis of voice diseases in patients treated in the Podlaski region].
AB  - Analysis of professional dysphonia in 309 patients treated in Phoniatric
      Outpatient Clinic of the (chair and) Department of Otolaryngology AM in Bialystok
      was performed. The teachers of primary and lower secondary schools were the
      majority of the patients. The teachers were compared with the 65 patients of
      other occupations. Additional harmful factors were excluded in both groups. In
      all patients' otolaryngologic, phoniatric and videostroboscopic examinations were
      completed. The analysis paid attention to functional and organic dysphonias. In
      the group of voice workers there were found early functional laryngeal disorders,
      which were progressive with the period of work. In other patients organic
      disorders were more common and occurred earlier than functional ones. The degree
      of dysphonia depended on laryngeal pathology, especially in case of functional
      dysphonia.

PMID- 15518426
TI  - [Value of dobutamine stress echocardiography for the diagnosis of coronary artery
      disease in women with aortic valve stenosis].
AB  - Dobutamine stress echocardiography (DSE) is widely used for diagnosis of coronary
      artery disease (CAD). However, data regarding the diagnosis of coronary artery
      disease in patients with moderately elevated maximal gradient across the stenosed
      aortic valve (AS) are limited. This study was designed to the value of DSE in the
      diagnosis of CAD in women with moderately elevated maximal gradient across the
      AS. PATIENTS AND METHODS: DSE was performed in 162 patients within the
      multicentre study. The group included 58 (mean age 61 +/- 13 years) females and
      104 (mean age 58 +/- 13 years) males. DSE was performed with step-wise infusion
      every three minutes (5, 10, 20, 30 and 40 microg/kg/min). If the target heart
      rate was not reached, a further dose of 40 mcg/kg/min. together with atropine
      0.25-1 mg was administered, in the absence of signs and symptoms of ischemia.
      Ischaemia was defined as new or worsened wall motion abnormalities at
      echocardiography. Coronarography was performed according to generally accepted
      indications. The significant coronary artery disease (>1 = 50% luminal diameter
      stenosis) of one of the major epicardial vessel was accepted as positive result
      for making the diagnosis of CAD. RESULTS: There was significant difference at
      rest between women and men with regard to left ventricular diastolic diameter
      (47.7 +/- 6.5 vs 55.6 +/- 8.8 mm), systolic diameter (30.1 +/- 7.9 vs 38.1 +/-
      11.5 mm), ejection fraction (67 +/- 12 vs 55 +/- 17%), wall motion score index
      (1.05 +/- 0.17 vs 1.22 +/- 0.36) p<0.001. There were also a significant
      difference in left ventricular mass index and diastolic septum diameter (131 +/-
      48 vs 152 +/- 46) and (12.5 + 2.7 vs 13.5 +/- 2.6 mm). Dobutamine peak dose was
      31 +/- 11 microg/kg/min. The mean heart rate, mean systolic pressure and
      diastolic pressure were 114 +/- 26/min, 143 +/- 26 and 81 +/- 15 mmHg
      respectively. Sensitivity, specificity, and accuracy of DSE for the diagnosis of
      CAD in women were 77.8%, 95.8% and 90.9%. Those in men were 72.7%, 78.8% and
      75.6%, respectively (NS). CONCLUSION: The diagnostic value of dobutamine stress
      echocardiography for the diagnosis of coronary artery disease in women with
      stenosed aortic valve is high. DSE is good method for the diagnosis.

PMID- 15518427
TI  - [Gastroesophagopharyngeal reflux in infants and children with recurrent symptoms
      of the upper respiratory tract].
AB  - Gastroesophageal reflux (GER) plays an important role in pathogenesis of
      recurrent/chronic disorders of the respiratory tract. Atypical symptoms of GER
      can be suggested to be cause of the otorhinolaryngological problems. For these
      last manifestations no cause-effect relationship has yet been proven. There are
      many therapeutic studies, in which treatment of GERD is examined for its impact
      on coexisting respiratory disorders. The aim of our study was to confirm the
      presence of acid reflux by using 24-hour intraesophageal pH monitoring. From the
      group of 29 patients with recurrent episodes of the pharyngitis, laryngitis and
      tracheitis, we evaluated 18 children aged 3 months to 8 years (mean, 4.23 +/-
      2.85) with coexisting reflux symptoms. The protocol included a parenteral
      interview, physical examination, roentgenograms of the chest and larynx,
      laryngoscopy, as well as 24-hour simultaneous proximal and distal esophageal pH
      monitoring. The most significant differences between examined patients and
      control subjects was noted in terms of the lowest pH value, number of reflux
      episodes and index reflux while pH dropped below 4. Every significant drop under
      pH 6 recorded in proximal esophagus was simultaneous with reflux episode in
      distal esophagus. We found increased both sensitivity and specificity of the
      simultaneous pH monitoring in the distal and proximal part of the esophagus
      comparing to monitoring by the single probe. We confirmed the presence of
      gastroesophagopharyngeal reflux in patients with recurrent disorders of pharynx,
      larynx and/or trachea.

PMID- 15518428
TI  - [Role of the hemostatic system in pathogenesis of atherosclerosis as the main
      etiology of coronary ischemia] [corrected].
AB  - Coronary artery disease is a leading cause of mortality in highly developed
      societies. This occurs in spite of growing therapeutic opportunities.
      Atherosclerosis begins as a functional or/and structural damage of endothelium,
      which in turn causes its discontinuation and impairs humoral and secreting
      function. Haemostasis plays an important role in the progression of
      atherosclerosis and development of cardiac complications--acute coronary
      syndromes. Research still continues to determine precisely role of each of
      haemostasis disorders in increased risk of coronary artery disease and its
      complications. The aim of this paper is to review the literature data concerning
      haemostatic risk factors and their role of development of coronary artery
      disease. Fibrinogen, thrombocytes, factor VII, factor VIII, von Willebrand factor
      (vWF), thrombomodulin (TM), plasminogen activator inhibitor--type 1 (PAI-1),
      tissue-plasminogen activator (t-PA) and other haemostatic factors, were described
      as more or less helpful in estimation of risk of occurrence of coronary artery
      disease and its cardiovascular complications. Only some of the described
      hematologic factors were verified so far in large prospective studies, and were
      recognized as independent risk factors of cardiovascular diseases.

PMID- 15518429
TI  - [Role of the hemostasis in unstable angina pectoris].
AB  - Haemostasis plays an important role in the development of cardiac complications-
      acute coronary syndromes. The thrombus formation in coronary arteries, related to
      unstable atherosclerotic plaque rupture is the basic pathogenesis of acute
      coronary syndromes. The balance between coagulation and fibrinolytic system
      influences on ruptured atherosclerotic plaque and following acute coronary
      syndrome. Critical narrow or total occlusion of the coronary artery could be a
      consequence of this interaction. Researches are continued to determine precisely
      role of haemostasis disorders in unstable angina pectoris. The aim of this paper
      is to review the literature data concerning haemostatic risk factors in unstable
      angina pectoris. Fibrinogen, thrombocytes, factor VIII, von Willebrand factor
      (vWF), thrombomodulin (TM), plasminogen activator inhibitor--type 1 (PAI-1),
      tissue-plasminogen activator (t-PA) and other haemostatic factors, play more or
      less essential role in unstable angina pectoris. However further investigations
      are needed to determine their utility and to search for new and better
      haemostatic factors of acute coronary syndromes.

PMID- 15518430
TI  - [Transplant coronary artery disease--treatment with statins].
AB  - Hypercholesterolemia is a common disorder after heart transplantation and my be
      associated with the development of transplant coronary artery disease. 3-hydroxy
      3-methylglutaryl coenzyme A reductase inhibitors (HMG CoA) are the most effective
      drugs to lower cholesterol level in transplant patients. However, interaction of
      immunosuppressants with HMG CoA inhibitors, which are metabolized by cytochrome P
      450, increase incidence of skeletal muscle myopathy and rhabdomyolysis.

PMID- 15518431
TI  - [Urotensin II--new peptide which regulates function of cardiovascular system].
AB  - Human urotensin II is one of the new peptide which regulates function of
      cardiovascular system. It stimulates cardiomyocytes and vascular smooth muscle
      hypertrophy and also shows inotropic properties. Urotensin II has the potential
      pathophysiological role in cardiovascular, lung and kidney diseases. The vascular
      function of this peptide in humans, however, has yet to be determined. Human
      urotensin II is an endocrine hormone with range vasoactive properties dependent
      on the anatomic site and the species. Preliminary results showed strong
      expression of urotensin II in the cardiomyocytes, and to a lesser extent in the
      vascular smooth muscle cells, endothelial cells, and inflammatory cells of
      patients with end-stage chronic heart failure. The development of selective human
      urotensin II antagonists may be of utility in the management of cardiovascular
      disorders.

PMID- 15518432
TI  - [Psychoprophylaxis in patients after coronary artery bypass graft operations].
AB  - The paper presented problems of quality of life and psychosocial functioning of
      patients following coronary artery bypass grafting operations. Possibilities of
      psychoprophylactic effects towards these patients and its efficacy were
      described.

PMID- 15518433
TI  - [Homocysteine as the factor of atherosclerosis risk].
AB  - A great number of epidemiologic and experimental results of scientific research
      led to the conclusion, that hyperhomocysteinemia could be possible risk factor
      for the cardiovascular diseases development in patients suffering from the
      homocysteinuria and in all the population, because of homocysteine's ability to
      the activation of the thrombogenesis processes and to the creation of the
      atherosclerotic changes. Furthermore, the elevated homocysteine concentration
      exacerbates the effects of the other atherosclerogenous factors, such as tobacco
      smoking or arterial hypertension. The increased mortality caused by the
      cardiovascular diseases was observed in patients with the homocysteine
      concentration elevated above 15 micromol/l on an empty stomach and 38 micromol/l
      after the methionine intake (the mortality was twice higher). The concentration
      aimed 10 to 15 micromol/l is assumed to be the normal high concentration. There
      were no screening researches led on the population for the showing the number of
      people with the increased homocysteine concentration, however such kind of
      investigation could be recommended in patients with diabetes, kidney diseases,
      family history with reported cardiovascular diseases, heart and other organs
      transplantation, and in patients with the constant intake medicaments increasing
      the homocysteine concentration. We have no results of prospective research
      conducted on the numerous patient group, which could document the profits
      resulted by the treatment of the hyperhomocysteinemia in the primary and
      secondary prophylactic of the cardiovascular disease.

PMID- 15518434
TI  - [Bartter's syndrome].
AB  - Bartter syndrome is an uncommon tubular disorder inherited as an autosomal
      recessive entity. It is associated with hypokalemic metabolic alkalosis with high
      renin and aldosterone plasma concentration with low or normal blood pressure.
      Recent studies have demonstrated genetic heterogeneity in Bartter syndrome.
      Mutations of two genes encoding the Na/K/2Cl cotransporter and potassium channel
      ROMK are responsible for clinical features of neonatal Bartter syndrome.
      Mutations of gen encoding the chloride channel ClC-Kb is identified as being
      causative for the classic Bartter syndrome. And dysfunction of Na/Cl
      cotransporter in the distal convoluted renal tubule is described as Gitelman
      syndrome.

PMID- 15518435
TI  - [Hormonal factors in etiology of common acne].
AB  - Common acne is steatorrhoeic chronic disease, to which specific is, among others,
      the presence of blackheads, papulopustular eruptions, purulent cysts and
      cicatrices. Such hormonal factors belong to elements inherent in etiology of the
      affection. Sebaceous glands have cell receptors on their surface for androgens.
      In etiopathogenesis of common/simple acne, a decisive role is played by a
      derivative of testosterone, i.e. 5-alpha-dihydrotestosterone (DHT). However, some
      experts are of opinion that there is no correlation between the increased
      intensity of common acne and other symptoms of hyperandrogenism. Numerous authors
      assume, however, that common acne-affected patients may be sometimes subjected to
      intense reactions caused by sebaceous glands against physiological androgens
      concentrations. Naturally, estrogens can inhibit release of such androgens. Under
      physiological conditions, natural progesterone does not conduct to
      intensification of the seborrhea, but the activity of sebum secretion may be
      triggered off by its synthetic counterparts. Hormonal etiology can be very
      distinctly visible in the steroid, androgenic, premenstrual, menopausal acne, as
      well as in juvenile acne and acne neonatorum. In case of females affected by
      acne, hormonal therapy should be persistently supported and consulted with
      dermatologists, endocrinologists and gynecologists. Antiandrogenic preparations
      are applied, such as: cyproterone acetate concurrently administered with
      estrogens and, as well as not so frequently with chlormadinone acetate
      (independently or during estrogenic therapy).

PMID- 15518436
TI  - [Stewart-Treves syndrome].
AB  - Angiosarcoma arising in the area of chronically lymphoedematous extremity is
      referred to as Stewart-Treves syndrome. In the world literature we can find about
      400 cases of Stewart-Treves syndrome occurring after treatment for breast cancer.
      There are also occasional case reports of Stewart-Treves syndrome within
      chronically lymphoedematous upper extremity not related to breast cancer
      treatment and within chronically lymphoedematous leg. Treatment of choice is wide
      surgical resection with clear surgical margins. Adjuvant radiotherapy is advised.
      Treatment outcomes are generally poor. 5 year survival is estimated at 10%.

PMID- 15518437
TI  - [Adjuvant and salvage radiotherapy after radical prostatectomy].
AB  - Currently radical prostatectomy remains the standard mode of treatment for
      patients with locally and localized stage of prostate cancer. On the other hand,
      after radical prostatectomy approximately 50% of patients have postoperative
      positive margin. Therefore implementation of effective mode of adjuvant
      radiotherapy treatment after radical prostatectomy plays important role in
      clinic. Currently available data, which evaluated the effectiveness of
      radiotherapy after radical prostatectomy are based on retrospective studies.
      These studies indicated that post-operative radiotherapy reduced the local
      recurrence rate but the influence on the patient's survival is unknown.
      Generally, the following factors are considered as prognostic for failure: the
      presence of pathologic T3 (pT3), positive surgical margin, preoperative
      concentration of prostatic specific antigen (PSA) above 25ng/ml, metastases to
      lymph nodes, Gleason >7. Radiotherapy is performed as typical adjuvant
      radiotherapy in case of pT3 or positive margin without rising of PSA level. This
      mode of treatment is efficient and gives the excellent local control rate but
      without marked influence on overall survival of patients. Another strategy, which
      is considered after radical prostatectomy, is salvage radiotherapy. This mode of
      treatment is introduced when the rising level of PSA and/or the pathological
      recurrence mass in the tumor bed is occurred. The efficacy of the salvage
      radiotherapy is lower than classical adjuvant radiotherapy. Still remain
      questions about the following issues: timing of radiotherapy, optimal dose,
      treatment technique, involved target for radiotherapy, and the role of adjuvant
      hormonal therapy. The last issue now is evaluating in the randomized clinical
      trial. In summary, currently until outcomes from well conducted randomized trials
      will available patients after radical prostatectomy with adverse significant
      factors for local recurrence or/and increased level of PSA should be considered
      for postoperative radiotherapy.

PMID- 15518438
TI  - [Improvement of public health care].
AB  - We discussed problems of health care in Poland and forms of doctors' professional
      training aiming to change present system of medical service.

PMID- 15518439
TI  - From research evidence to context: the challenge of individualizing care.

PMID- 15518440
TI  - Systematic reviews of diagnostic test evaluations: what's behind the scenes?

PMID- 15518442
TI  - Exercise training reduced ischemic events more than percutaneous coronary
      intervention in stable coronary artery disease.

PMID- 15518441
TI  - Cardiac outcomes occurred more frequently with PCI than CABG or medical therapy
      in coronary artery disease.

PMID- 15518443
TI  - Review: lactulose or lactitol may improve hepatic encephalopathy but may be less
      effective than antibiotics.

PMID- 15518444
TI  - Cardiac resynchronization therapy reduced all-cause death and hospitalization in
      chronic heart failure.

PMID- 15518445
TI  - A prophylactic cardioverter-defibrillator prevented sudden death from arrhythmia
      in nonischemic cardiomyopathy.

PMID- 15518446
TI  - Review: exercise-based cardiac rehabilitation reduces all-cause and cardiac
      mortality in coronary heart disease.

PMID- 15518447
TI  - Review: Exercise training in patients with heart failure is safe.

PMID- 15518448
TI  - Perioperative use of atorvastatin reduced cardiovascular events in patients
      having vascular surgery.

PMID- 15518449
TI  - Review: lipid-lowering agents reduce cardiovascular events in type 2 diabetes.

PMID- 15518450
TI  - Review: prophylactic use of Vitamin D reduces falls in older persons.

PMID- 15518451
TI  - Training informal caregivers of patients with stroke improved patient and
      caregiver quality of life and reduced costs.

PMID- 15518452
TI  - Adding aspirin to clopidogrel increased bleeding without reducing recurrent
      ischemic vascular events in high-risk patients.

PMID- 15518453
TI  - Combination disease-modifying antirheumatic drug therapy reduced work disability
      in early rheumatoid arthritis.

PMID- 15518454
TI  - Intensive management reduced disease activity in rheumatoid arthritis.

PMID- 15518455
TI  - Noninvasive positive-pressure ventilation increased risk for death in respiratory
      failure after extubation.

PMID- 15518456
TI  - Review: adults who require inhaled corticosteroids benefit from a moderate
      starting dose.

PMID- 15518457
TI  - Review: antileukotriene agents at licensed doses plus inhaled corticosteroids do
      not reduce asthma exacerbations more than inhaled corticosteroids alone.

PMID- 15518458
TI  - Fondaparinux was as effective as (noninferior to) enoxaparin in acute symptomatic
      deep venous thrombosis.

PMID- 15518459
TI  - Helicobacter pylori eradication had no effect on heartburn or gastroesophageal
      reflux in H pylori infection.

PMID- 15518460
TI  - Review: several factors are associated with the performance of D-dimer assays for
      detecting deep venous thrombosis.

PMID- 15518461
TI  - Review: of the various D-dimer assays, negative ELISA results are most useful for
      excluding a diagnosis of deep venous thrombosis or pulmonary embolism.

PMID- 15518462
TI  - Men had greater risk for recurrent venous thromboembolism than women.

PMID- 15518464
TI  - A bedside prediction tool predicted all-cause mortality 6 months after discharge
      for the acute coronary syndrome.

PMID- 15518463
TI  - A low or high ankle brachial index increased the risk for all-cause mortality in
      Native Americans.

PMID- 15518465
TI  - The recalibration of the Framingham functions to the Chinese population improved
      coronary heart disease risk estimates.

PMID- 15518466
TI  - Why do drying films crack?
AB  - Understanding the mechanism by which films fail during drying is the first step
      in controlling this natural process. Previous studies have examined the spacing
      between cracks with predictions made by assuming a balance between elastic energy
      released with a surface energy consumed. We introduce a new scaling for the
      spacing between cracks in drying dispersions. The scaling relates to the distance
      that solvent can flow, to relieve capillary stresses, as a film fails. The
      scaling collapses data for a range of evaporation rates, film thicknesses,
      particle sizes, and materials. This work identifies capillary pressures, induced
      by packed particle fronts travelling horizontally across films, as responsible
      for the failure in dried films.

PMID- 15518467
TI  - Immobilization and recovery of au nanoparticles from anion exchange resin: resin
      bound nanoparticle matrix as a catalyst for the reduction of 4-nitrophenol.
AB  - The immobilization of gold nanoparticles in anion exchange resin and their
      quantitative retrieval by means of a cationic surfactant, cetylpyridinium
      chloride, is studied. The resin-bound gold nanoparticles (R-Au) have been used
      successfully as a solid-phase catalyst for the reduction of 4-nitrophenol by
      sodium borohydride. At the end of the reaction, the solid matrix remains
      activated and separated from the product. The recycling of catalyst particles
      after the quantitative reduction of 4-nitrophenol and the recovery of gold
      nanoparticles with unaffected particle morphology from the resin-bound gold
      nanoparticle entity have been reported.

PMID- 15518468
TI  - Fast directed motion of "fakir" droplets.
AB  - In this Letter, we report on the motion of water droplets on surfaces decorated
      with molecular gradients comprising semifluorinated (SF) organosilanes. SF
      molecular gradients deposited on flat silica substrates facilitate faster motion
      of water droplets relative to the specimens covered with an analogous hydrocarbon
      gradient. Further increase in the drop speed is achieved by advancing it along
      porous substrates coated with the SF wettability gradients. The results of our
      experiments are in quantitative agreement with a simple scaling theory that
      describes the faster liquid motion in terms of reduced friction at the
      liquid/substrate interface.

PMID- 15518469
TI  - Photocontrolled gel-to-sol-to-gel phase transitioning of meta-substituted
      azobenzene bisurethanes through the breaking and reforming of hydrogen bonds.
AB  - An azobenzene derivative substituted at its meta positions with two urethane
      moieties linked to two cholesteryl ester units forms a gel that exhibits sol-gel
      phase transitions upon photoirradiation as a result of trans-cis isomerization of
      the azobenzene unit. During the sol-gel phase transitions, hydrogen bonds, which
      are partly responsible for stabilizing the gels, are broken or reformed. Using
      circular dichroism spectroscopy, we detected asymmetrical fibrous networks in the
      aggregates of these gelators.

PMID- 15518470
TI  - Polymer-induced fractal patterns of [60]fullerene containing poly(methacrylic
      acid) in salt solutions.
AB  - Well-defined water-soluble pH-responsive [60]fullerene (C60) containing
      poly(methacrylic acid) (PMAA-b-C60) was synthesized using the atom transfer
      radical polymerization technique. By varying pH and salt concentration, different
      types of fractal patterns at nano- to microscopic dimensions were observed for
      negatively charged PMAA-b-C60, while such structure was not observed for
      positively charged poly(2-dimethylaminoethyl methacrylate)-b-C60. We demonstrated
      that negatively charged fullerene containing polymeric systems can serve as
      excellent nanotemplates for the controlled growth of inorganic crystals at the
      nano- to micrometer length scale, and the possible mechanism was proposed.

PMID- 15518471
TI  - Controlled production of monodisperse double emulsions by two-step droplet
      breakup in microfluidic devices.
AB  - A microfluidic device having both hydrophobic and hydrophilic components is
      exploited for production of multiple-phase emulsions. For producing water-in-oil
      in-water (W/O/W) dispersions, aqueous droplets ruptured at the upstream
      hydrophobic junction are enclosed within organic droplets formed at the
      downstream hydrophilic junction. Droplets produced at each junction could have
      narrow size distributions with coefficients of variation in diameter of less than
      3%. Control of the flow conditions produces variations in internal/external
      droplet sizes and in the internal droplet number. Both W/O/W emulsions (with two
      types of internal droplets) and oil-in-water-in-oil emulsions were prepared by
      varying geometry and wettability in microchannels.

PMID- 15518472
TI  - Facile fabrication of AgCl@polypyrrole-chitosan core-shell nanoparticles and
      polymeric hollow nanospheres.
AB  - A one-step sequential method for preparing AgCl@polypyrrole-chitosan core-shell
      nanoparticles and subsequently the formation of polypyrrole-chitosan hollow
      nanospheres is reported. The formation of the core and the shell is performed in
      one reaction medium almost simultaneously. Transmission electron microscopy (TEM)
      images show the presence of core-shell nanoparticles and hollow nanospheres.
      Ultraviolet-visible (UV-vis) studies reveal that AgCl was formed first followed
      by polypyrrole. X-ray diffration (XRD) and UV-vis studies show that AgCl was
      present in the core-shell nanoparticles and could be removed completely from the
      core.

PMID- 15518473
TI  - "Direct" detection and separation of DNA using nanoporous alumina filters.
AB  - The concept of using alumina nanoporous filters (AAO) modified with DNA for
      "label-free" detection and separation/purification of the target ss-DNA is
      demonstrated. The high surface density of DNA (4 x 10(12) cm(-2)) and high
      efficiency of hybridization (ca. 70%) in combination with increased effective
      surface area make this system very attractive for development of various ss-DNA
      (or RNA) detection methods. Moderate transparency of AAO in the UV and IR regions
      allows direct detection of DNA hybridization by optical and IR absorption. Close
      to the quantitative efficiency of binding the target ss-DNA from solution using a
      single pass through the modified filter is observed.

PMID- 15518474
TI  - Inverse and reversible switching gradient surfaces from mixed polyelectrolyte
      brushes.
AB  - We report on a thin polyelectrolyte film (mixed polyelectrolyte brush) with a
      gradual change of the composition (ratio between two different oppositely charged
      surface-grafted weak polyelectrolytes) across the sample. The gradient of surface
      composition creates a gradient in surface charge density and, consequently, a
      gradient of the wetting behavior. The gradient film is sensitive to a pH signal
      and can be reversibly switched via pH change.

PMID- 15518475
TI  - Anomalous IR properties of nanostructured films created by square wave potential
      on an array of Pt microelectrodes: an in situ microscope FTIRS study of CO
      adsorption.
AB  - Thin films of different nanostructures on an array of nine Pt microelectrodes
      were prepared by applying a square wave potential treatment for different times
      (tau). It has been measured from the cyclic voltammetric studies that the
      relative surface roughness of the films was increased slightly and reached a
      maximal value of about 2.5. SEM studies demonstrated that with the increase of
      tau, the growth of island-shaped Pt crystallites on the films led to the
      formation of plumelike crystallites that can reach about 2-3.5 microm in length
      when tau exceeded 70 min. In situ microscope FTIR reflection spectroscopic
      studies illuminated that CO adsorbed on the array yielded different anomalous IR
      features. With the increase of tau, the direction of the CO L band (linearly
      bonded CO) was transformed from the negative-going direction (normal IR
      adsorption) to bipolar (Fano-like spectral line shape) and finally to the
      positive-going direction (abnormal IR adsorption). The intensity of the CO L band
      was enhanced significantly and a maximal enhancement factor of about 33 was
      measured when tau was 40 min; the center of the CO L band and the Stark tuning
      rate also showed regular changes. This study demonstrated that specific
      nanostructures of Pt thin films can be prepared through a square wave potential
      treatment for different times and revealed the intrinsic relationship between
      anomalous IR properties and surface nanostructures of the thin films.

PMID- 15518476
TI  - Effects of soluble surfactants on the deformation and breakup of stretching
      liquid bridges.
AB  - Surfactants are routinely used to control the breakup of drops and jets in many
      applications such as inkjet printing, crop spraying, and DNA or protein
      microarraying. The breakup of surfactant-free drops and jets has been extensively
      studied. By contrast, little is known about the closely related problem of
      interface rupture when surfactants are present. Solutions of a nonionic
      surfactant, pentaethylene glycol monododecyl ether, or C12E5, in water and in 90
      wt % glycerol/water are used to show the effects of surfactant and viscosity on
      the deformation and breakup dynamics of stretching liquid bridges. Equilibrium
      surface tensions for both solutions can be fitted with the Langmuir-Szyskowski
      equation. All experiments have been done at 24 degrees C. The critical micelle
      concentrations for C12E5 are 0.04 and 0.4 mM in water and the glycerol/water
      solution, respectively. With high-speed imaging, the dynamic shapes of bridges
      held captive between two rods of 3.15 mm diameter are captured and analyzed with
      a time resolution of 0.1-1 ms. The bridge lengths are 3.15 mm initially and about
      5-7 mm at pinch-off. Breakup occurs after stretching for about 0.2-0.3 s,
      depending on the solution viscosity and the surfactant concentration. When the
      liquid bridges break up, the volume of the sessile drop left on the bottom rod is
      about 3 times larger than that of the pendant drop left on the top rod. This
      asymmetry is due to gravity and is influenced by the equilibrium surface
      tensions. Surfactant-containing low-viscosity water bridges are shown to break up
      faster than surfactant-free ones because of the effect of gravity. With or
      without surfactant, water bridges form satellite drops. Surfactant-containing
      high-viscosity glycerol/water bridges break up more slowly than surfactant-free
      ones because of strong viscous effects. Moreover, the shapes of the sessile drops
      close to breakup exhibit a "pear-like" tip; whether a satellite forms depends on
      the surface age of the bridge before stretching commences. These unexpected
      effects arising from the addition of surfactants are due to the capillary
      pressure reduction and Marangoni flows linked to dynamic surface tension.

PMID- 15518477
TI  - Structural evolution in cationic micelles upon incorporation of a polar organic
      dopant.
AB  - Micelles of cetyltrimethylammonium bromide (CTAB), when doped with increasing
      levels of 4-ethylphenol, show microstructural transitions from spherical micelles
      to elongated wormlike micelles, disks, and subsequently to globular and then to
      tubular vesicles. Wormlike micelles are observed at a dopant-to-CTAB molar ratio
      of 1:3. At higher dopant ratios (1:1), globular vesicles are observed which
      transition to tubular vesicles when the dopant becomes the predominant species at
      a ratio of 3:1. These transitions are reflected in small-angle neutron scattering
      analysis and, interestingly, can be directly observed through cryo-transmission
      electron microscopy. The para-substituted phenol is interfacially active and
      modulates interfacial curvature of the micelles. The observations of
      microstructure modifications have relevance to the synthesis of mesoporous
      materials using CTAB as the template.

PMID- 15518478
TI  - Heat capacity of transfer of (Ethylene oxide)13-(propylene oxide)30-(ethylene
      oxide)13 from water to the aqueous anionic surfactant solutions at 298 K. A
      quantitative treatment.
AB  - Heat capacities of transfer (DeltaCpt) of unimeric (ethylene oxide)13-(propylene
      oxide)30-(ethylene oxide)13 from water to the aqueous surfactant solutions as
      functions of the surfactant concentrations (mS) were determined at 298 K. The
      surfactants investigated are sodium hexanoate, sodium heptanoate, sodium
      octanoate, sodium undecanoate, and sodium dodecanoate. For short alkyl chain
      surfactants, the profiles of the DeltaCpt versus mS curves show maxima and
      minima; for long alkyl chain surfactants, the maximum becomes sharper and moved
      to lower mS values whereas the minimum tends to disappear. These experimental
      trends are different from those of the enthalpy in agreement with the fact that
      heat capacity, being the derivative of enthalpy with respect to temperature,
      reflects additional terms generated by temperature change on the equilibria in
      solution. On the basis of a thermodynamic model recently proposed by us for
      properties first derivatives of Gibbs free energy, a quantitative treatment of
      the experimental data was done. Such an approach assumes that even in the dilute
      surfactant region monomers of surfactant associate with unimeric copolymer
      generating surfactant-copolymer aggregation complexes and, whenever the
      surfactant achieves the conditions for the micellization, the formation of
      copolymer-micelle mixed aggregates takes place. The equation derived for the heat
      capacity of transfer is more complex than that for the enthalpy because it
      contains five additional terms due to the shift of the equilibria induced by the
      temperature change. It turned out that these contributions, evaluated by using
      the equilibrium constants and the associated enthalpies, cannot be neglected for
      a quantitative treatment of the experimental data. The minimizing procedure
      provided the heat capacity changes for the formation of the surfactant-copolymer
      aggregation complexes and the copolymer-micelle mixed aggregates.

PMID- 15518479
TI  - Kinetic study in water-ethylene glycol cationic, zwitterionic, nonionic, and
      anionic micellar solutions.
AB  - The spontaneous hydrolysis of phenyl chloroformate was studied in water-ethylene
      glycol, EG, cationic, zwitterionic, nonionic, and anionic micellar solutions, the
      surfactants being tetradecyltrimethylammonium bromide, tetradecyl-N,N-dimethyl-3
      ammonio-1-propanesulfonate, tricosaoxyethylene glycol ether, and sodium dodecyl
      sulfate. The dependence of the observed rate constant on surfactant concentration
      as well as on the percentage by weight of EG, varying from 0 to 50 wt %, was
      investigated. Information about changes in the critical micelle concentrations,
      in the micellar ionization degrees (for ionic surfactants), in the aggregation
      numbers, and in the polarity of the interfacial region of the micelles upon
      changing the weight percent of EG was obtained through conductivity, surface
      tension, spectroscopic, and fluorescence measurements. A simple pseudophase model
      was adequate to rationalize the kinetic data. Micellar medium effects were
      explained by considering charge-charge interactions and polarity, ionic strength,
      and water content in the micellar interfacial region. The acceleration of the
      reaction produced by an increase in the amount of EG present in the mixture was
      explained on the basis of the substantial decrease in the equilibrium binding
      constant of phenyl chloroformate molecules to the micelles, resulting in the
      contribution of the reaction taking place in the bulk water-EG phase being more
      important. The weight percent of EG did not substantially influence the rate
      constant in the micellar pseudophase.

PMID- 15518480
TI  - Hybrid fluorocarbon-hydrocarbon CO2-philic surfactants. 1. synthesis and
      properties of aqueous solutions.
AB  - Six different hybrid fluorocarbon-hydrocarbon (F-H) sulfate and sulfonate
      surfactants, with variations in the relative F/H carbon chain length, have been
      synthesized and characterized in aqueous solution. These compounds have been
      targeted for potential activity in densified CO2. Tensiometric data and chemical
      analyses were consistent with surfactants of high chemical purity. Fluorination
      in terms of the F/H ratio exerts a strong control over all the surfactant
      physicochemical properties, including critical micelle concentrations (cmc's) and
      adsorption isotherms. One of these partially fluorinated surfactants (the
      sulfonate phi-F6H4) achieves very low surface tensions in water (gamma(cmc)
      approximately 19 mN m(-1)) more reminiscent of fully fluorinated double-chain
      compounds. Detailed 19F NMR studies revealed that omega'-CF3 groups can exhibit
      separate signals for monomeric and micellized forms, hence facilitating cmc
      determinations. Small-angle neutron scattering investigations confirmed the
      presence of ellipsoidal or extended disklike micelles, depending on the F-H chain
      asymmetry. For example, a symmetric hybrid F8H8 generates disklike micelles,
      whereas chain asymmetry in F8H4 or phi-F6H4 tends to drive cylindrical
      aggregation structures. These changes are consistent with variations in the
      surfactant packing parameter caused by the different chain F/H ratios. Hence,
      adsorption and aggregation are shown to respond in a predictable way to the
      molecular structure of these unusual surfactants.

PMID- 15518481
TI  - Hybrid fluorocarbon-hydrocarbon CO2-philic surfactants. 2. formation and
      properties of water-in-CO2 microemulsions.
AB  - Hybrid fluorocarbon-hydrocarbon (F-H) sulfate surfactants are shown to be
      efficient stabilizers in water-in-CO2 (w/c) microemulsions. The chain structure
      and F-H ratio affect the regions of P-T phase stability and aggregation structure
      in these w/c phases. High-pressure near-infrared spectroscopy and small-angle
      neutron scattering measurements of microemulsified water provide evidence for the
      stabilization of w/c microemulsion droplets. The relative lengths of the two
      chains were found to influence the favored aggregation structure: for symmetric
      chain surfactants (F8H8, F7H7) spherical reverse micelles are present, but for
      asymmetric chain surfactants (F7H4, F8H4) extended cylinder aggregates form.
      These changes in aggregation are consistent with different surfactant packing
      parameters owing to the controlled variations in molecular structure.
      Furthermore, the general order of w/c phase transition pressures (F8H8 < F7H7 and
      F8H4 < F7H4) is in line with estimations of surfactant fractional free volume, as
      proposed by Johnston et al. (J. Phys. Chem. B 2004, 108, 1962-1966). Studies of
      adsorption at the poly(dimethylsiloxane)-water interface are shown to be valuable
      for assessing the CO2-philicity of new surfactants. All in all, the symmetric
      F8H8 and F7H7 analogues are seen to be the most efficient compounds from this
      class for applications in CO2.

PMID- 15518482
TI  - Hydrogel microspheres: influence of chemical composition on surface morphology,
      local elastic properties, and bulk mechanical characteristics.
AB  - Hydrogel microspheres, beads, and capsules of uniform size, differing in their
      chemical composition, have been prepared by electrostatic complex formation of
      sodium alginate with divalent cations and polycations. These have served as model
      spheres to study the influence of the chemical composition on both surface
      characteristics and bulk mechanical properties. Resistance to compression
      experiments yielding the compression work clearly identified differences as a
      function of the composition, with forces at maximal compression in the range of
      34-455 mN. The suitability and informative value of atomic force microscopy have
      been confirmed for the case where surface characterization is performed in a
      liquid environment equivalent to physiological conditions. Surface imaging and
      mechanical response to indentation revealed different average surface roughness
      and Young's moduli for all hydrogel types ranging from 0.9 to 14.4 nm and from
      0.4 to 440 kPa, respectively. The hydrogels exhibited pure elastic behavior.
      Despite a relatively high standard deviation, resulting from both surface and
      batch heterogeneity, nonoverlapping ranges of Young's moduli were reproducibly
      identified for the selected model spheres. The findings indicate the reliability
      of contact mode atomic force microscopy to quantify local surface properties,
      which may have an impact on the biocompatibility of alginate-based hydrogel
      materials of different composition and conditions of preparation. Moreover, it
      seems that local elastic properties and bulk mechanical characteristics are
      subject to analogous composition influences.

PMID- 15518483
TI  - Mixed spherical and wormlike micelles: a contrast-matching study by small-angle
      neutron scattering.
AB  - Small-angle neutron scattering studies were used to investigate the effect of
      adding an alcohol ethoxylate nonionic surfactant (d-C12E20) to aqueous solutions
      of a cationic surfactant, erucyl bis(hydroxyethyl) methylammonium chloride
      (EHAC), with and without salt (KCl). The systematic use of contrast-matching, by
      alternately highlighting or hiding one of the surfactants, confirms that mixed
      micelles are formed. In salt-free solutions, mixed spherical micelles are formed
      and a core-shell model combined with a Hayter-Penfold potential was used to
      describe the data. The core radius is dominated by the EHAC tails and the outer
      radius determined by the ethoxylate headgroups of the nonionic surfactant.
      Addition of KCl promotes micellar growth; however, results of varying the solvent
      contrast revealed that when the nonionic surfactant is incorporated into the
      wormlike structure micellar breaking is promoted. Thus, mixed wormlike micelles
      with shorter contour lengths compared to the pure EHAC worms are formed.

PMID- 15518484
TI  - Modulation with acetonitrile of the dynamics of guest binding to the two distinct
      binding sites of cholate aggregates.
AB  - Bile salt aggregates are supramolecular systems containing two different binding
      sites. The effect of the addition of acetonitrile on the specificity and dynamics
      of guest binding to the two binding sites of cholate aggregates was studied. The
      protection of guests included in the aggregate from interaction with ions in the
      aqueous phase was evaluated from quenching of the singlet and triplet excited
      states of guest molecules bound to the cholate aggregates. The dynamics of guest
      binding to the primary and secondary binding sites of the cholate aggregates were
      determined at increasing acetonitrile mole fractions. The structure of the
      aggregates was not significantly altered provided the cholate concentrations were
      higher than 20 mM and the acetonitrile mole fraction did not exceed 0.033 (9.1%
      v/v). These results show that acetonitrile can be used to modulate the solubility
      of guests in the aggregates and to manipulate the residence time of guests in the
      primary and secondary binding sites.

PMID- 15518485
TI  - Temperature-actuated changes in wettability at elastomer/water interfaces.
AB  - Surface modification of 1,4-polybutadiene and cis-1,4-polyisoprene to introduce
      polar functional groups provided surfaces that reconstructed reversibly against
      water as a function of temperature. These surfaces became hydrophobic in contact
      with hot water, but their original hydrophilicity returned upon equilibration
      against cold water. Repeated cycling between hot and cold water, however, led to
      a damping of this reversibility. A series of parallel experiments on both the
      interfacial and bulk behavior of these elastomers strongly indicated that this
      damping was due to the alignment of extended interfacial chains during
      temperature cycling and to a decay of the restoring force on the interfacial
      chains under extension. These studies thus demonstrate that the interfacial
      behavior of elastomers can display close analogies to the bulk viscoelastic
      properties of the solid.

PMID- 15518486
TI  - Surface hydrophobicity of fluorinated block copolymers enhanced by supercritical
      carbon dioxide annealing.
AB  - Supercritical carbon dioxide (scCO2) annealing enhances the hydrophobicity of the
      surfaces of asymmetric perfluorinated block copolymers. X-ray photoelectron
      spectroscopy (XPS) and contact angle measurement reveal that the surface domains
      of the fluorinated block (PF) of poly[styrene-block-4
      (perfluorooctylpropyloxy)styrene] (PS-PF) become thicker than those annealed in a
      vacuum. Consequently, the contact angles of water on the surfaces of PS-PF block
      copolymers significantly increase after the scCO2 annealing compared to those
      annealed in a vacuum. The surface hydrophobicity enhanced by the scCO2 annealing
      is related to the thickness of the surface PF domain and the conformation of the
      PF block.

PMID- 15518487
TI  - Frictional dynamics of fluorine-terminated alkanethiol self-assembled monolayers.
AB  - The frictional dynamics of fluorine-terminated alkanethiol (S(CH2)8CF3) self
      assembled monolayers (SAMs) on gold are studied using molecular dynamics
      simulations. The simulations treat the interactions between two SAMs on flat
      surfaces. The structure and frictional behavior are investigated as a function of
      applied pressure (200 MPa to 1 GPa) for a shear velocity of 2 m/s and compared to
      methyl-terminated alkanethiol SAMs. The maximum adhesive pressure between the
      SAMs is 220 MPa for both end groups. In agreement with experiments on the
      molecular scale, the shear stress and the coefficient of friction for CF3
      terminated alkanethiols are larger than for CH3-terminated alkanethiols. The main
      source for the difference is primarily the tighter packing of the fluorinated
      terminal group resulting in a higher degree of order. The molecular scale
      coefficient of friction is correlated with the degree of order among all the
      systems.

PMID- 15518488
TI  - Wetting behavior of water droplets on hydrophobic microtextures of comparable
      size.
AB  - The wetting behavior of water droplets on periodically structured hydrophobic
      surfaces was investigated. The effect of structure geometry, roughness, and
      relative pore fraction on the contact angles was investigated experimentally for
      droplets of size comparable to the size of the structures. It was found that
      surface geometry may induce a transition from groove-filling and Wenzel-like
      behavior to nonfilling of surface grooves and consequential Cassie-Baxter
      behavior. Numerical calculations of the free energy of these systems suggest that
      the equilibrium behavior is in line with the experimental observations. The
      observations may serve as guidelines for the design of surfaces with the desired
      wetting behavior.

PMID- 15518489
TI  - Frontal photopolymerization for microfluidic applications.
AB  - Frontal photopolymerization (FPP) offers numerous advantages for the rapid
      prototyping of microfluidic devices. Quantitative utilization of this method,
      however, requires a control of the vertical dimensions of the patterned resist
      material. To address this fundamental problem, we study the ultraviolet (UV)
      photopolymerization of a series of multifunctional thiolene resists through a
      combination of experiments and analytical modeling of the polymerization fronts.
      We describe this nonlinear spatio-temporal growth process in terms of a "minimal"
      model involving an order parameter phi(x, t) characterizing the extent of monomer
      to-polymer conversion, the optical attenuation T(x, t), and the solid front
      position h(t). The latter exhibits an induction time (or equivalent critical UV
      dose) characterizing the onset of frontal propagation. We also observe a novel
      transition between two logarithmic rates of growth, determined by the Beer
      Lambert attenuation constants mu(0) and mu(infinity) of the monomer and fully
      polymerized material, respectively. The measured frontal kinetics and optical
      transmission of the thiolene resist materials are consistent with our
      photopolymerization model, exhibiting both "photodarkening" and "photoinvariant"
      polymerization. This is apparently the first observation of photodarkening
      reported in FPP. On the basis of these results, multilevel fluidic devices with
      controlled height are readily fabricated with modulated illumination. A
      representative two-level microfluidic device, incorporating a chaotic mixer, a T
      junction, and a series of controlled flow constrictions, illustrates the
      practical versatility of this fabrication method.

PMID- 15518490
TI  - Elucidation of the deposition processes and spatial structures of alkanethiol and
      arylthiol molecules adsorbed on Pt111 electrodes with in situ scanning tunneling
      microscopy.
AB  - In situ scanning tunneling microscopy (STM) was used to examine the spatial
      structures of n-alkane thiols (1-hexanethiol, 1-nonanethiol, and 1
      octahexanethiol) and arylthiols (benzenethiol and 4-hydroxybenzenethiol) adsorbed
      on well-ordered Pt111 electrodes in 0.1 M HClO4. The electrochemical potential
      and molecular flux were found to be the dominant factors in determining the
      growth mechanisms, final coverages, and spatial structures of these organic
      adlayers. Depending on the concentrations of the thiols, deposition of self
      assembled monolayers (SAMs) followed either the nucleation-and-growth mechanism
      or the random fill-in mechanism. Low and high thiol concentrations respectively
      produced two ordered structures, (2 x 2) and (square root of 3 x square root of
      3)R30 degrees , between 0.05 and 0.3 V. On average, an ordered domain spanned 500
      A when the SAMs were made at 0.15 V, but this dimension shrank substantially once
      the potential was raised above 0.3 V. This potential-induced order-to-disorder
      phase transition resulted from a continuous deposition of thiols, preferentially
      at domain boundaries of (square root of 3 x square root of 3 x )R30 degrees
      arrays. All molecular adlayers were completely disordered by 0.6 V, and this
      restructuring event was irreversible with potential modulation. Since all thiols
      were arranged in a manner similar to that adopted by sulfur adatoms (Sung et al.
      J. Am. Chem. Soc. 1997, 119, 194), it is likely that they were adsorbed mainly
      through their sulfur headgroups in a tilted configuration, irrespective of the
      coverage. Both the sulfur and phenyl groups of benzenethiol admolecules gave rise
      to features with different corrugation heights in the molecular-resolution STM
      images. All thiols were adsorbed strongly enough that they remained intact at a
      potential as negative as -1.0 V in 0.1 M KOH.

PMID- 15518491
TI  - Accurate height and volume measurements on soft samples with the atomic force
      microscope.
AB  - The suitability of three common atomic force microscope (AFM) imaging modes for
      quantitative height and volume measurements on soft samples was investigated. The
      height and volume of rehydrated human metaphase chromosomes in liquid were
      measured using the contact mode, the tapping mode, and the force mapping mode. In
      both the contact and tapping modes, the measured height and volume strongly
      depended on the imaging setpoint that sets the imaging force. Measurement
      deviations up to 50% were observed. The force mapping mode, on the other hand,
      yielded reproducible height and volume measurements independent of the imaging
      force. It is therefore suggested that the force mapping mode should be used
      whenever the height or volume of soft samples need to be accurately determined.

PMID- 15518492
TI  - Ultrathin binary grafted polymer layers with switchable morphology.
AB  - Polymer surface layers comprised of mixed chains grafted to a functionalized
      silicon surface with a total layer thickness of only 1-3 nm are shown to exhibit
      reversible switching of their structure. Carboxylic acid-terminated polystyrene
      (PS) and poly (butyl acrylate) (PBA) were chemically attached to a silicon
      surface that was modified with an epoxysilane self-assembled monolayer by a
      "grafting to" routine. While one-step grafting resulted in large, submicron
      microstructures, a refined, two-step sequential grafting procedure allowed for
      extremely small spatial dimensions of PS and PBA domains. By adjusting the
      grafting parameters, such as concentration of each phase and molecular weight,
      very finely structured surfaces resulted with roughly 10-nm phase domains and
      less than 0.5-nm roughness. Combining the glassy PS and the rubbery PBA, we
      implemented a design approach to fabricate a mixed brush from two immiscible
      polymers so that switching of the surface nanomechanical properties is possible.
      Post-grafting hydrolysis converted PBA to poly(acrylic acid) to amplify this
      switching in surface wettability. Preliminary tribological studies showed a
      difference in wear behavior of glassy and rubbery surface layers. Such switchable
      coatings have practical applications as surface modifications of complex
      nanoscale electronic devices and sensors, which is why we restricted total
      thickness for potential nanoscale gaps.

PMID- 15518493
TI  - Bovine serum albumin adsorption onto colloidal Al2O3 particles: a new model based
      on zeta potential and UV-vis measurements.
AB  - We investigated the adsorption of bovine serum albumin (BSA) on colloidal Al2O3
      particles in an aqueous environment. Changes in the zeta potential of the Al2O3
      particles upon the adsorption of BSA were measured using an electro-acoustic
      technique. The mass of protein adsorbed was determined by using UV-vis
      spectroscopy. The change of the isoelectric point of the Al2O3 powder-protein
      suspension was found to be a function of adsorbed protein mass. It was shown that
      approximately one monolayer of BSA was needed to fully mask the surface and to
      compromise the charge of Al2O3. From titration experiments it follows that about
      30-36% of the negatively charged groups of the protein form bonds with the
      protonated and charged Al2O3 surface. On the basis of our observations we
      introduced a new adsorption model for BSA on Al2O3 particles.

PMID- 15518494
TI  - Layering transitions and Schlieren textures in Langmuir films of two organic
      radicals.
AB  - Two paramagnetic radicals have been investigated in terms of their film-forming
      properties at the air-water interface. Although the radicals failed to display
      any mesomorphic behavior in the bulk, they were found prone to built-up
      multilayer films on the Langmuir trough. The molecules seem to dimerize in the
      upper layers of the films that exhibit striking Schlieren textures when observed
      with Brewster angle microscopy. These Schlieren textures, together with the
      ability to form multilayers, indicate that the molecules came close to displaying
      smectic mesomorphism. A tentative model of the layers' structure is proposed, and
      a suggestion for synthesizing new molecules with actual mesomorphism is offered.
      The presented results show that the study of the behavior of molecules at the air
      water interface can shed a new light on their behavior in the bulk and help in
      the design of new magnetic mesogens.

PMID- 15518495
TI  - Chemical reactions with upright monolayers of cruciform pi-systems.
AB  - The study below details the synthesis and self-assembly of new cruciform pi
      systems and their in situ chemical reactions in monolayer films. Analysis of the
      packing in the crystal structure of one of these unusually shaped molecules
      reveals that the terphenyl arm, which is twisted out of conjugation, makes edge
      to-face contact with neighboring molecules aligning the conjugated bisoxazole
      arms in rows. In self-assembled monolayers on metal surfaces, these cruciform pi
      systems present reactive groups at the film/air interface. Films that present
      aldehyde functionality react with aromatic anilines to give surface-bound imines.
      Dimers that are >4.5 nm in length and contain a conjugated imine linkage can be
      made in situ on gold substrates through this strategy.

PMID- 15518496
TI  - Can contact-angle measurements determine the disjoining pressure in liquid
      nanofilms on rigid substrates?
AB  - The disjoining pressure of lubricant nanofilms used in the magnetic recording
      industry controls the equilibrium wetting, the dynamics of film restoration, and
      the evaporation kinetics of the film. It has been claimed that by measuring the
      contact angle of nonpolar and polar liquids on lubricant films, the disjoining
      pressure can be extracted using the method of Girafalco and Good, and such
      analyses have appeared in the literature. The approximations underlying the
      method have been discussed before in the literature. In view of the importance of
      measuring disjoining pressure in nanofilms of lubricants, it is timely to revisit
      these assumptions to understand the validity of the contact-angle method
      presently in use. We re-derive the relevant equations using a thermodynamic
      interaction-energy approach which is free of the problems inherent in the
      original derivation and make explicit the assumptions which must be made in the
      derivation. General interaction energy arguments are then invoked to demonstrate
      that it does not appear possible to obtain the disjoining pressure in the film
      from contact-angle measurements in an unambiguous manner.

PMID- 15518497
TI  - A facile photochemical surface modification technique for the generation of
      microstructured fluorinated surfaces.
AB  - We describe a simple photochemical process which allows fluoropolymers to be
      chemically bound at room temperature onto SiO2 surfaces. To achieve this, at
      first a benzophenone silane is used to form a self-assembled monolayer on the
      surface of the substrate, which is subsequently coated with the fluoropolymer and
      irradiated with UV light of wavelength 365 nm. Using this very simple approach,
      we have been able to create ultrahydrophobic surfaces with very low surface free
      energies together with a good degree of control in thickness and composition as
      well as strong adhesion to the monolayer. The use of a UV-based process to attach
      the films on SiO2 surfaces opens the door for photopatterning of surfaces with
      fluorinated and nonfluorinated compounds to yield well-defined microstructures
      with spatial control of the wetting properties of the substrates.

PMID- 15518498
TI  - Structural properties of oligonucleotide monolayers on gold surfaces probed by
      fluorescence investigations.
AB  - We present optical investigations on the conformation of oligonucleotide layers
      on Au surfaces. Our studies concentrate on the effect of varying surface coverage
      densities on the structural properties of layers of 12- and 24mer single-stranded
      DNA, tethered to the Au surface at one end while being labeled with a fluorescent
      marker at the opposing end. The distance-dependent energy transfer from the
      marker dye to the metal surface, which causes quenching of the observed
      fluorescence, is used to provide information on the orientation of the DNA
      strands relative to the surface. Variations in the oligonucleotide coverage
      density, as determined from electrochemical quantification, over 2 orders of
      magnitude are achieved by employing different preparation conditions. The
      observed enhancement in fluorescence intensity with increasing DNA coverage can
      be related to a model involving mutual steric interactions of oligonucleotides on
      the surface, as well as fluorescence quenching theory. Finally, the applicability
      of the presented concepts for investigations of heterogeneous monolayers is
      demonstrated by means of studying the coadsorption of mercaptohexanol onto DNA
      modified Au surfaces.

PMID- 15518499
TI  - Modification of aliphatic self-assembled monolayers by free-radical-dominant
      plasma: the role of the plasma composition.
AB  - Modification of octadecanethiolate self-assembled monolayers on Au by nitrogen
      oxygen or argon-oxygen downstream microwave plasma with a low oxygen content
      (estimated below several percent) has been studied by synchrotron-based high
      resolution X-ray photoelectron spectroscopy and water contact angle measurements.
      For both types of plasma, the primary processes were found to be the loss of
      conformational and orientational order and the oxidation of the alkyl matrix and
      headgroup-substrate interface. At the same time, the film modification occurred
      much faster and with different intermediates for the nitrogen plasma than for the
      argon plasma. The reasons for these differences are considered in terms of the
      different reactivities and different efficiencies of the energy transfer between
      the plasma constituents in these two types of plasma.

PMID- 15518500
TI  - Transformation diagrams for the collapse of a phospholipid monolayer.
AB  - The kinetics of phase transitions in three-dimensional bulk materials are
      commonly presented in transformation diagrams. Time-temperature transformation
      (TTT) and continuous-cooling-transformation (CCT) diagrams plot the time required
      to transform specific fractions of the material to the new phase by cooling below
      a transition temperature. Transformation occurs isothermally for the TTT diagrams
      and during continuous cooling through a range of temperatures for CCT curves.
      Here we present analogous transformation diagrams for two-dimensional monolayers,
      which collapse at the equilibrium spreading pressure (pi e) to form a three
      dimensional bulk phase. Time-surface pressure-transformation (TpiT) diagrams give
      the time required for specific fractions of the film to collapse when surface
      pressure is constant, and continuous-compression-transformation diagrams give the
      same information when surface pressure varies continuously. The diagrams,
      constructed here from previously reported data for 1-palmitoyl-2-oleoyl
      phosphatidylcholine, provide insights into the behavior of the films. The TpiT
      diagrams successfully predict the existence and approximate magnitude of a
      threshold rate for compressing the films to high surface pressures above pi e and
      the approximate shape of isotherms obtained with different rates of interfacial
      compression. The diagrams also caution that the behavior of mixed monolayers,
      explained previously in terms of compositional changes, can instead result from
      collapse that varies with surface pressure. Finally, the similarity between the
      shapes of the TTT and TpiT diagrams, with the time for transformation passing
      through a minimum and then increasing as the systems deviate further from
      equilibrium, suggests that analogous mechanisms determine the behavior of both
      systems.

PMID- 15518501
TI  - Thermo-reversible swelling of thin hydrogel films immobilized by low-pressure
      plasma.
AB  - Thin films of graft copolymers consisting of poly(N-isopropylacrylamide)
      (PNiPAAm) or poly(N,N-diethylacrylamide) (PDEAAm) as polymer backbone and
      poly(ethyleneglycol) as side chains were cross-linked on fluoropolymer substrates
      by low-pressure plasma treatment. All immobilized polymers exhibit a lower
      critical solution temperature between 34 and 40 degrees C. The swelling and
      collapsing of the hydrogels was examined with temperature-dependent spectroscopic
      ellipsometry. Two time ranges of swelling were observed: a fast 'dynamic' and a
      slow 'equilibrium' swelling. The dynamic swelling occurs within minutes or less,
      whereas the equilibrium swelling needs several days to complete. The surface
      bound hydrogels show a shift in the transition temperature toward lower
      temperatures compared with the behavior in solution. Full reversibility of the
      dynamic swelling/collapsing was found, but the temperature scan exhibits a
      hysteresis between heating and cooling cycles. The PNiPAAm-containing hydrogels
      show a sharper transition compared to the PDEAAm-containing hydrogels, which is
      almost linear over a wide temperature range.

PMID- 15518502
TI  - Quantitative information on pore size distribution from the tangents of
      comparison plots.
AB  - The comparison plot obtained from the nitrogen adsorption data has a similar
      shape to that of the curve of accumulating pore volume of a solid. The intrinsic
      nature of this relation is discussed. It is known that the derivatives of the
      accumulating pore volume with respect to the pore size are the pore size
      distribution (PSD) of the solid. Thus, the tangent curve of the comparison plot
      can display, at least qualitatively, the PSD of a solid, over a wide range of
      pore sizes (from approximately 1 to 50 nm) because the comparison plot is
      applicable to both micropores and mesopores. Quantitative pore structure
      information can be derived from the comparison plots by establishing a
      relationship between the t value and the pore size from the samples with uniform
      pore structure and known pore sizes, such as MCM-41 and alumina pillared clay
      samples. A calculation procedure to derive quantitative PSD from the comparison
      plots is suggested, giving reasonable results. This study proposes concise and
      reliable methods based on the comparison plots to derive information on pore
      structure in porous solids.

PMID- 15518503
TI  - Effects of omega-functional groups on pH-dependent reductive desorption of
      alkanethiol self-assembled monolayers.
AB  - Self-assembled monolayers (SAMs) of alkanethiols having various terminal groups
      on their omega-positions were formed on a Au111 electrode, and their reductive
      desorption was studied by linear sweep voltammetry, focusing on effects of
      solution pH on the desorption behavior. The peak potentials (Ep) of cathodic
      waves representing reductive desorption were found to be reflected by the pKa
      value of the thiol group and were negatively shifted with an increase in pH of
      the electrolyte solution. The magnitude of the pH dependency of Ep was greatly
      influenced by the hydrophobicity of the terminal groups. In the cases of
      alkanethiol SAMs having pH-sensitive terminal groups such as carboxyl and amino
      groups, their basicity was estimated from bending points appearing in the pH
      titration profile of Ep. This method allows direct determination of not only the
      pKa value of the arrayed groups but also that of the groups dissolved in solution
      simultaneously. The pKa values of the arrayed carboxyl groups in SAMs were larger
      by ca. 3 pH units than their original ones, while those for amino groups were
      smaller by ca. 2 pH units.

PMID- 15518505
TI  - Thermoresponsive poly(N-isopropylacrylamide) copolymers: contact angles and
      surface energies of polymer films.
AB  - Surface properties of poly(N-isopropylacrylamide) (PNIPAM) copolymer films were
      studied by contact angle measurements and optical and atomic force microscopy. We
      prepared a series of copolymers of N-isopropylacrylamide with N-tert
      butylacrylamide (NtBA) in order of increasing hydrophobicity. The measurements of
      the advancing contact angle of water at 37 degrees C were hampered by the
      observation of a distinct stick/slip pattern on all polymers in the series with
      the exception of poly(NtBA) (PNtBA). We attributed this behavior to the film
      deformation by the vertical component of liquid surface tension leading to the
      pinning of the moving contact line. This was confirmed by the observation of a
      ridge formed at the pinned contact line by optical microscopy. However,
      meaningful contact (without the stick/slip pattern and with a time-independent
      advancing contact angle) angles for this thermoresponsive polymer series could be
      obtained with carefully selected organic liquids. We used the Li and Neumann
      equation of state to calculate the surface energy and contact angles of water for
      all polymers in the series of copolymers and van Oss, Chaudhury, and Good (vOCG)
      acid-base theory for PNtBA. The surface energies of the thermoresponsive polymers
      were in the range of 38.9 mJ/m2 (PNIPAM) to 31 mJ/m2 (PNtBA) from the equation of
      state approach. The surface energy of PNtBA calculated using vOCG theory was 29.0
      mJ/m2. The calculated contact angle for PNIPAM (74.5 +/- 0.2 degrees ) is
      compared with previously reported contact angles obtained for PNIPAM-modified
      surfaces.

PMID- 15518506
TI  - Contact-angle hysteresis on super-hydrophobic surfaces.
AB  - The relationship between perturbations to contact angles on a rough or textured
      surface and the super-hydrophobic enhancement of the equilibrium contact angle is
      discussed theoretically. Two models are considered. In the first (Wenzel) case,
      the super-hydrophobic surface has a very high contact angle and the droplet
      completely contacts the surface upon which it rests. In the second (Cassie
      Baxter) case, the super-hydrophobic surface has a very high contact angle, but
      the droplet bridges across surface protrusions. The theoretical treatment
      emphasizes the concept of contact-angle amplification or attenuation and
      distinguishes between the increases in contact angles due to roughening or
      texturing surfaces and perturbations to the resulting contact angles. The theory
      is applied to predicting contact-angle hysteresis on rough surfaces from the
      hysteresis observable on smooth surfaces and is therefore relevant to predicting
      roll-off angles for droplets on tilted surfaces. The theory quantitatively
      predicts a "sticky" surface for Wenzel-type surfaces and a "slippy" surface for
      Cassie-Baxter-type surfaces.

PMID- 15518504
TI  - Surface-dependent transitions during self-assembly of phospholipid membranes on
      mica, silica, and glass.
AB  - Formation of supported membranes by exposure of solid surfaces to phospholipid
      vesicles is a much-used technique in membrane research. Freshly cleaved mica,
      because of its superior flatness, is a preferred support, and we used
      ellipsometry to study membrane formation kinetics on mica. Neutral dioleoyl
      phosphatidylcholine (DOPC) and negatively charged dioleoyl
      phosphatidylserine/dioleoyl-phosphatidylcholine (20% DOPS/80% DOPC) vesicles were
      prepared by sonication. Results were compared with membrane formation on silica
      and glass, and the influence of stirring, buffer, and calcium was assessed.
      Without calcium, DOPC vesicles had a low affinity (Kd approximately 30 microM)
      for mica, and DOPS/DOPC vesicles hardly adsorbed. Addition of calcium promptly
      caused condensation of the adhering vesicles, with either loss of excess lipid or
      rapid additional lipid adsorption up to full surface coverage. Vesicle-mica
      interactions dominate the adsorption process, but vesicle-vesicle interactions
      also seem to be required for the condensation process. Membranes on mica proved
      unstable in Tris-HCl buffer. For glass, transport-limited adsorption of DOPC and
      DOPS/DOPC vesicles with immediate condensation into bilayers was observed, with
      and without calcium. For silica, vesicle adsorption was also rapid, even in the
      absence of calcium, but the transition to condensed layers required a critical
      surface coverage of about 50% of bilayer mass, indicating vesicle-vesicle
      interaction. For all three surfaces, additional adsorption of DOPC (but not
      DOPS/DOPC) vesicles to condensed membranes was observed. DOPC membranes on mica
      were rapidly degraded by phospholipase A2 (PLA2), which pleads against the role
      of membrane defects as initial PLA2 targets. During degradation, layer thickness
      remained unchanged while layer density decreased, in accordance with recent
      atomic force microscopy measurements of gel-phase phospholipid degradation by
      PLA2.

PMID- 15518507
TI  - Disruption of viscoelastic beta-lactoglobulin surface layers at the air-water
      interface by nonionic polymeric surfactants.
AB  - Nonequilibrium interfacial layers formed by competitive adsorption of beta
      lactoglobulin and the nonionic triblock copolymer PEO99-PPO65-PEO99 (F127) to the
      air-water interface were investigated in order to explain the influence of
      polymeric surfactants on protein film surface rheology and foam stability.
      Surface dilatational and shear rheological methods, surface tension measurements,
      dynamic thin-film measurements, diffusion measurements (from fluorescence
      recovery after photo bleaching), and determinations of foam stability were used
      as methods. The high surface viscoelasticity, both the shear and dilatational, of
      the protein films was significantly reduced by coadsorption of polymeric
      surfactant. The drainage rate of single thin films, in the presence of beta
      lactoglobulin, increased with the amount of added F127, but equilibrium F127
      films were found to be thicker than beta-lactoglobulin films, even at low
      concentration of the polymeric surfactant. It is concluded that the effect of the
      nonionic triblock copolymer on the interfacial rheology of beta-lactoglobulin
      layers is similar to that of low molecular weight surfactants. They differ
      however in that F127 increases the thickness of thin liquid films. In addition,
      the significant destabilizing effect of low molecular weight surfactants on
      protein foams is not found in the investigated system. This is explained as due
      to long-range steric forces starting to stabilize the foam films at low
      concentrations of F127.

PMID- 15518508
TI  - Shear and dilatational relaxation mechanisms of globular and flexible proteins at
      the hexadecane/water interface.
AB  - Proteins adsorbed at fluid/fluid interfaces influence many phenomena: food
      emulsion and foam stability (Murray et al. Langmuir 2002, 18, 9476 and Borbas et
      al. Colloids Surf., A 2003, 213, 93), two-phase enzyme catalysis (Cascao-Pereira
      et al. Biotechnol. Bioeng. 2003, 83, 498; 2002, 78, 595), human lung function
      (Lunkenheimer et al. Colloids Surf., A 1996, 114, 199; Wustneck et al.; and
      Banerjee et al. 2000, 15, 14), and cell membrane mechanical properties (Mohandas
      et al. 1994, 23, 787). Time scales important to these phenomena are broad,
      necessitating an understanding of the dynamics of biological macromolecules at
      interfaces. We utilize interfacial shear and dilatational deformations to study
      the rheology of a globular protein, lysozyme, and a disordered protein, beta
      casein, at the hexadecane/water interface. Linear viscoelastic properties are
      measured using small amplitude oscillatory flow, stress relaxation after a sudden
      dilatational displacement, and shear creep response to probe the rheological
      response over broad experimental time scales. Our studies of lysozyme and beta
      casein reveal that the interfacial dissipation mechanisms are strongly coupled to
      changes in the protein structure upon and after adsorption. For beta-casein, the
      interfacial response is fluidlike in shear deformation and is dominated by
      interfacial viscous dissipation, particularly at low frequencies. Conversely, the
      dilatational response of beta-casein is dominated by diffusion dissipation at low
      frequencies and viscous dissipation at higher frequencies (i.e., when the
      experimental time scale is faster than the characteristic time for diffusion).
      For lysozyme in shear deformation, the adsorbed protein layer is primarily
      elastic with only a weak frequency dependence. Similarly, the interfacial
      dilatational moduli change very little with frequency. In comparison to beta
      casein, the frequency response of lysozyme does not change substantially after
      washing the protein from the bulk solution. Apparently, it is the irreversibly
      adsorbed fraction that dominates the dynamic rheological response for lysozyme.
      Using stress relaxation after a sudden dilatational displacement and shear creep
      response, the characteristic time of relaxation was found to be 1000 s in both
      modes of deformation. The very long relaxation time for lysozyme likely results
      from the formation of a glassy interfacial network. This network develops at high
      interfacial concentrations where the molecules are highly constrained because of
      conformation changes that prevent desorption.

PMID- 15518509
TI  - Adsorption and activity of Candida rugosa lipase on polypropylene hollow fiber
      membrane modified with phospholipid analogous polymers.
AB  - Efforts have recently been made toward the study of interactions of phospholipid
      with various enzymes. It seems that phospholipids may be directly involved in
      regulating the enzyme activity. In this work, three phospholipid analogous
      polymers (PAPs), containing hydrophobic octyloxy, dodecyloxy, and octadecyloxy
      groups (abbreviated as 8-PAP, 12-PAP, and 18-PAP, respectively), were tethered on
      polypropylene hollow fiber microfiltration membrane (PPHFMM) to create a
      biocompatible interface for lipase immobilization. Lipase from Candida rugosa was
      immobilized on these PPHFMMs by adsorption. The adsorption capacity, activity,
      and thermal stability of enzyme on the PAP-modified PPHFMMs were compared with
      those of enzyme on the nascent ones. It was found that, as for the PAP-modified
      PPHFMMs, the adsorption capacities of lipase are lower than that of the nascent
      ones, while the activity retention of immobilized lipase increases from 57.5% to
      74.1%, 77.5%, and 83.2% respectively for the 8-PAP-, 12-PAP-, and 18-PAP-modified
      PPHFMMs. In addition, the experimental results of thermal stability show that the
      residual activity of the immobilized lipase at 50 degrees C for 2 h is 62% for
      the 8-PAP-modified PPHFMM, 59% for the 12-PAP-modified PPHFMM, and 66% for the 18
      PAP-modified PPHFMM, which are also higher than that of the nascent ones.

PMID- 15518510
TI  - Evaluation of the adhesion properties of inorganic materials with high surface
      energies.
AB  - With the aim of checking the validity of methods for characterizing the adhesion
      between inorganic materials with high surface energies, the properties of the
      adhesion between an inorganic material (indium tin oxide (ITO)) and model
      surfaces with various surface energies (Cl-, NH2-, CH(3)-, and CF3-functionalized
      surfaces) were evaluated using atomic force microscopy (AFM) and the Johnson
      Kendall-Roberts (JKR) apparatus. For this purpose, the AFM tip and the JKR lens
      were modified with ITO using radio frequency (rf) magnetron sputtering. The work
      of adhesion between the ITO coating and each model surface was estimated using
      AFM and the JKR apparatus and compared with the result obtained from contact
      angle measurements. The adhesion forces determined from the force-displacement
      curves (AFM) were found to agree with the predictions of the Derjaguin-Muller
      Toporov (DMT) theory. The JKR equation used in the interpretation of the JKR
      experiments was modified by taking into account the differences between the
      surface and bulk moduli of the ITO-coated poly(dimethylsiloxane) (PDMS) lens. The
      ratio of the surface modulus to the bulk modulus we used in this modified JKR
      equation was obtained by determining the slope of the attracting part of the
      force-displacement curve. The values of the work of adhesion calculated using the
      modified JKR equation were also found to agree with the values obtained from
      contact angle measurements. We conclude that the two methods using AFM and the
      JKR apparatus can be used in the evaluation of the work of adhesion between
      inorganic materials with high surface energies such as metal and metal oxide
      surfaces.

PMID- 15518511
TI  - Surface plasmon near-field imaging of very thin microstructured polymer layers.
AB  - We report on the near-field imaging of microstructured polymer layers deposited
      on an homogeneous metal thin film on which a surface plasmon mode is excited. The
      microstructures in the polymer layers are designed by electron beam lithography,
      and the near-field imaging is performed with a photon scanning tunneling
      microscope (PSTM). We show that, despite their very small height, the
      microstructures can be conveniently imaged with a PSTM thanks to the field
      enhancement at the surface of the metal thin film supporting the surface plasmon.
      The influence of the illumination conditions on the contrast of the PSTM images
      is discussed. In particular, we show that both the field enhancement and the near
      field intensity distribution around the microstructures depend dramatically upon
      the illumination conditions, leading to the conclusion that the PSTM is well
      suited for spatially resolved near-field surface plasmon sensing purposes.

PMID- 15518512
TI  - Surface restructuring behavior of various types of poly(dimethylsiloxane) in
      water detected by SFG.
AB  - Surface structures of several different poly(dimethylsiloxane) (PDMS) materials,
      tetraethoxysilane-cured hydroxy-terminated PDMS (TEOS-PDMS), platinum-cured vinyl
      terminated PDMS (Pt-PDMS), platinum-cured vinyl-terminated poly(diphenylsiloxane)
      co-poly(dimethylsiloxane) (PDPS-co-PDMS), and PDMS-co-polystyrene (PDMS-co-PS)
      copolymer in air and water have been investigated by sum frequency generation
      (SFG) vibrational spectroscopy. The SFG spectra collected from all PDMS surfaces
      in both air and water are dominated by methyl group stretches, indicating that
      all the surfaces are mainly covered by methyl groups. Other than surface
      dominating methyl groups, some -Si-CH2-CH2- moieties on the Pt-PDMS surface have
      also been detected in air, which are present at cross-linking points. Information
      about the average orientation angle and angle distribution of the methyl groups
      on the PDMS surface has been evaluated. Surface restructuring of the methyl
      groups has been observed for all PDMS surfaces in water. Upon contacting water,
      the methyl groups on all PDMS surfaces tilt more toward the surface. The detailed
      restructuring behaviors of several PDMS surfaces in water and the effects of
      molecular weight on restructuring behaviors have been investigated. For
      comparison, in addition to air and water, surface structures of PDMS materials
      mentioned above in a nonpolar solvent, FC-75, have also been studied. By
      comparing the different response of phenyl groups to water on both PDPS-co-PDMS
      and PS-co-PDMS surfaces, we have demonstrated how the restructuring behaviors of
      surface phenyl groups are affected by the structural flexibility of the molecular
      chains where they are attached.

PMID- 15518513
TI  - Enhancement of electrochemical activity by small-sizing the vinylferrocene
      immobilized polystyrene latex particles.
AB  - Voltammetry of vinylferrocene (VFc)-immobilized polystyrene(PS)-based latex
      particles was carried out in aqueous suspensions by changing the size of latex
      particles in order to investigate the dependence of the electroactivity of the
      particles on their size. The anodic peak current was controlled by diffusion of
      the latex. The voltammetric peak currents increased with an increase in the
      diameter of PS latex particles for a given analytical concentration of the
      particles, exhibiting the dependence on 1.5 powers of the diameter of the
      particles. The increase can be explained in terms of combination of the uniform
      distribution of VFc in the particle, the partial charge transfer, and the Stokes
      Einstein equation for diffusion coefficients. The oxidation of VFc occurs in the
      restricted domain (0.07 microm) from a contact point of the particle with the
      electrode. The overall reaction mechanism is diffusion of the particle to the
      electrode, partial oxidation to VFc+, release of VFc+ from the particle to the
      solution, and reduction of the released VFc+.

PMID- 15518514
TI  - In situ STM imaging and direct electrochemistry of Pyrococcus furiosus ferredoxin
      assembled on thiolate-modified Au111 surfaces.
AB  - We have addressed here electron transfer (ET) of Pyrococcus furiosus ferredoxin
      (PfFd, 7.5 kDa) in both homogeneous solution using edge plane graphite (EPG)
      electrodes and in the adsorbed state by electrochemistry on surface-modified
      single-crystal Au111 electrodes, This has been supported by surface microscopic
      structures of PfFd monolayers, as revealed by scanning tunneling microscopy under
      potential control (in situ STM). Direct ET between PfFd in phosphate buffer
      solution, pH 7.9, and EPG electrodes is observed in the presence of promoters.
      Neomycin gives rise to a pair of redox peaks with a formal potential of ca -430
      mV (vs SCE), corresponding to [3Fe-4S]1+/0. The presence of an additional
      promoter, which can be propionic acid, alanine, or cysteine, induces a second
      pair of redox peaks at approximately -900 mV (vs SCE) arising from [3Fe-4S]0/1-.
      A robust neomycin-PfFd complex was detected by mass spectrometry. The results
      clearly favor an ET mechanism in which the promoting effect of small organic
      molecules is through formation of promoter-protein complexes. The interaction of
      PfFd with small organic molecules in homogeneous solution offers clues to confine
      the protein on the electrode surface modified by the same functional group
      monolayer and to address diffusionless direct electrochemistry, as well as
      surface microstructures of the protein monolayer. PfFd molecules were found to
      assemble on either mercaptopropionic acid (MPA) or cysteine-modified Au111
      surfaces in stable monolayers or submonolayers. Highly ordered (2 radical 3 x
      5)R30 degrees cluster structures with six MPA molecules in each cluster were
      found by in situ STM. Individual PfFd molecules on the MPA layer are well
      resolved by in situ STM. Under Ar protection reversible cyclic voltammograms were
      obtained on PfFd-MPA/Au111 and PfFd-cysteine/Au111 electrodes with redox
      potentials of -220 and -201 mV (vs SCE), respectively, corresponding to the
      [Fe3S4]1+/0 couple. These values are shifted positively by 200 mV relative to
      homogeneous solution due to interactions between the promoting layers and the
      protein molecules. Possible mechanisms for such interactions and their ET
      patterns are discussed.

PMID- 15518515
TI  - Single-electron charging features of larger, dodecanethiol-protected gold
      nanoclusters: electrochemical and scanning tunneling microscopy studies.
AB  - In this report, we demonstrate the single-electron charging features of larger
      sized (ca. 3.72 nm) Au nanoclusters protected with dodecanethiol [approximate
      composition, Au1415(RS)328] using combined electrochemical and scanning tunneling
      microscopic (STM) studies. In particular, these nanoclusters show a highly
      populated single-electron charging peak in voltammetric experiments, where the
      calculated capacitance is in good agreement with the experimentally obtained
      value of 1.6 aF. In comparison to the voltammetric studies, STM measurements over
      a single Au particle on the highly oriented pyrolytic graphite surface reveal
      nonlinear current-voltage (I-V) characteristics with a large central gap,
      signifying single-electron-transfer features. The I-V results demonstrate a clear
      Coulomb blockade effect with a central gap of around 0.2 eV, which is in good
      agreement with the orthodox theory for the double barrier tunnel junction system.
      The standard heterogeneous electron-transfer rate constant estimated from
      impedance measurements is found to be of 7.97 x 10(-6) cm.s(-1), suggesting that
      the process is very sluggish. Furthermore, diffusion coefficient (Dc) values
      calculated from chronoamperometry and impedance measurements are in good
      agreement with theoretically calculated values using the modified Stokes-Einstein
      equation. The electron-transfer rate constant estimated from cyclic voltammograms
      of adsorbed monolayer protected Au nanoclusters is found to be about 2 s(-1),
      which is slower than that reported for its smaller analogues.

PMID- 15518516
TI  - Electrodeposition of mesoporous semimetal and magnetic metal films from lyotropic
      liquid crystalline phases.
AB  - Mesoporous semimetal bismuth film and magnetic metal nickel and cobalt thin films
      have been electrodeposited from hexagonal or lamellar structured lyotropic liquid
      crystalline phases with polyoxyethylene surfactant. The liquid crystalline
      templates are characterized by low-angle X-ray diffraction (XRD) and polarized
      light optical microscopy (POM). The metal films are characterized by low-angle
      and wide-angle XRD, scanning electron microscopy (SEM), and transmission electron
      microscopy (TEM). The magnetic measurements on the mesoporous nickel and cobalt
      films are shown to have higher coercivity (Hc) than the nonporous polycrystalline
      films.

PMID- 15518517
TI  - (S)-cysteine chemisorption on Cu110, from the gas or liquid phase: an FT-RAIRS
      and XPS study.
AB  - (S)-Cysteine has been deposited on a Cu110 surface from sublimation of a
      crystalline phase. The surface was characterized by Fourier transform reflection
      absorption infrared spectroscopy (FT-RAIRS) during exposure and compared to the
      same copper surface after immersion into cysteine solutions at various pH values.
      X-ray photoelectron spectroscopy (XPS) measurements provided a chemical
      characterization of the surface at certain stages. The combination of these two
      techniques highlighted the importance of the cysteine "source" for the adsorbed
      form of the molecules and the mode of interaction. The zwitterionic amino acid
      was found to be predominant after adsorption at pH values close to the
      isoelectric point (IEP) of the molecule but also when the layer was formed in the
      vapor phase. This state was very sensitive to the atmosphere, contained an excess
      of hydroxyls, and/or underwent reduction into the anionic form when in contact
      with water or air. Weakly bound cysteine or cystine molecules, formed in the
      adsorbed phase, were considered to explain the average thickness of the adsorbed
      layer that was close to 20 A. As expected, immersion in very acidic or very basic
      solutions led to cationic and anionic forms, respectively.

PMID- 15518518
TI  - Reversible intercalation of large-capacity hemoglobin into in situ prepared
      titanate interlayers with enhanced thermal and organic medium stabilities.
AB  - The exfoliated single-layer titanate can rapidly restack and reversibly release
      heme protein simply by adjustment of the pH value. The composites have regularly
      layered structure and powdery morphology by their ideal layer-to-layer assembly,
      which provides the titanate nanosheet an unusual specific intercalation capacity
      of 5900 mg g(-1) for the protein. The bound and released proteins keep active
      relative to the intact protein. The hemoglobin thermal and organic solvent
      stabilities are improved by the protective environment of the titanate host.

PMID- 15518519
TI  - Interactions of dendrimers with selected amino acids and proteins studied by
      continuous wave EPR and Fourier transform EPR.
AB  - Interactions of polyamidoamine dendrimers, termed Gn, where n indicates the
      generation (=number of amidoamine layers), at different protonation levels with
      selected amino acids and proteins have been investigated by means of continuous
      wave electron paramagnetic resonance (cw-EPR) and pulsed-EPR (electron spin-echo
      = ESE) analyses. A low-generation dendrimer (G2) and a high-generation one (G6)
      were labeled with nitroxides for the EPR measurements. Gly, Glu, Arg, and Leu
      were selected as representative of neutral(zwitterionic)-polar, acidic, basic,
      and low-polar amino acids, respectively. The water-soluble proteins alpha
      chymotrypsin and albumin were selected on the basis of a basic and an acidic
      isoelectric point, respectively. The cw-EPR spectra were analyzed by computing
      the line shapes to extract information about the dendrimer-biomolecule
      interactions. In general, dendrimers at a high protonation level interact
      stronger with amino acids than those at a low level of protonation. However, even
      for highly protonated dendrimers, a synergistic effect between hydrophilic and
      hydrophobic interactions promoted the formation of stable Gn-amino acid adducts,
      as demonstrated by the enhanced interactions with Leu. As expected from acid-base
      interactions, stable adducts were formed between Arg and highly protonated
      dendrimers and between Glu and low level protonated dendrimers. The relatively
      strong dendrimer interactions with the protein chymotrypsin and the poor
      interactions of dendrimers with albumin demonstrated that the protonated amino
      groups of the dendrimers are predominantly involved in the interactions with
      these proteins and indicated a significant role in the interactions with the
      dendrimers of the hydrophobic external residues of chymotrypsin. Computer-aided
      analysis of the ESE experiments was consistent with the cw-EPR results and
      supported the conclusion of a partial complexation of the nitroxides of the
      dendrimer with Leu and alpha-chymotrypsin.

PMID- 15518520
TI  - Effect of macromolecular crowding on DNA:Au nanoparticle bioconjugate assembly.
AB  - DNA:Au nanosphere bioconjugates have applications in biosensing and in the bottom
      up assembly of materials. These bioconjugates can be selectively assembled into
      three-dimensional aggregates upon addition of complementary DNA oligonucleotides
      and can be dissociated by heating above a melting transition temperature at which
      the DNA duplexes are denatured. Herein we describe the impact of polymeric
      solutes on the thermal denaturation behavior of DNA:Au nanoparticle bioconjugate
      assemblies. Polymeric solutes can dramatically impact biochemical reactions via
      macromolecular crowding. Poly(ethylene glycol)s (PEGs) and dextrans of varying
      molecular weights were used as crowding reagents. While both PEG and dextran
      increased the stability of DNA:Au aggregates, melting transition temperatures in
      the presence of PEG were impacted more significantly. Polymer molecular weight
      was less important than polymer chemistry and weight percent in solution. For a
      high (15%) weight percent of PEG, aggregation was observed even in the absence of
      complementary oligonucleotides. These results underscore the importance of
      polymer chemistry in addition to physical volume exclusion in macromolecular
      crowding and point to the importance of understanding these effects when
      designing biorecognition-based nanoparticle assembly schemes in complex matrixes
      (i.e., any involving polymeric solutes).

PMID- 15518521
TI  - Patterning adjacent supported lipid bilayers of desired composition to
      investigate receptor-ligand binding under shear flow.
AB  - To achieve efficient targeting, carriers containing either drugs or imaging
      agents must have surface properties that promote binding to targets yet at the
      same time block rapid immune system clearance. Here we describe a versatile
      technique that allows simultaneous comparison of the effects of carrier surface
      composition on binding properties under identical flow conditions. Parallel lanes
      of supported lipid bilayers that mimic the surface of liposomal delivery vehicles
      are formed using the vesicle fusion method in microfluidic channels created via
      standard soft lithography techniques. Vesicle stock solutions are premixed and
      injected into lanes formed by a poly(dimethylsiloxane) (PDMS) stamp reversibly
      sealed to a glass slide to create adjacent lanes of distinct composition. After
      removing the stamp, an adsorbed layer of bovine serum albumin (BSA) is used to
      prevent bilayer spreading before assembling the patterned substrate into a flow
      chamber for binding studies. Advantages of this method include easy and rapid
      preparation of bilayers with desired compositions from an unlimited number of
      lipid types, choice of feature size, time-stable features, and low nonspecific
      binding. Feature sizes on the order of tens of microns allow multiple
      compositions to be analyzed in one field of view, thereby reducing the number of
      experiments, ensuring identical flow conditions, and enabling simultaneous
      incorporation of controls. We show that the presence of a long poly(ethylene
      glycol) (PEG) tether (MW 2000) between the lipid and ligand results in higher
      detachment resistances as compared to a short six-carbon spacer.

PMID- 15518522
TI  - Electrochemical deposition of silver in room-temperature ionic liquids and its
      surface-enhanced Raman scattering effect.
AB  - The use of room-temperature ionic liquids (RTILs) as media for electrochemical
      application is very attractive. In this work, the electrochemical deposition of
      silver was investigated at a glassy carbon electrode in hydrophobic 1-n-butyl-3
      methylimidazolium hexafluorophosphate (BMIMPF6) and hydrophilic 1-n-butyl-3
      methylimidazolium tetrafluoroborate (BMIMBF4) RTILs and in KNO3 aqueous solution
      by cyclic voltammetric and potentiostatic transient techniques. The voltammograms
      showed the presence of reduction and oxidation peaks associated with the
      deposition and dissolution of silver from AgBF4 in both BMIMPF6 and BMIMBF(4),
      resembling the redox behavior of AgNO3 in KNO3 aqueous solution. A crossover loop
      was observed in all the cyclic voltammograms of these electrochemical systems,
      indicating a nucleation process. From the analysis of the experimental current
      transients, it was shown that the electrochemical deposition process of silver in
      these media was characteristic of 3D nucleation with diffusion-controlled
      hemispherical growth, and the silver nucleation closely followed the response
      predicted for progressive nucleation in BMIMPF6 and instantaneous nucleation in
      KNO3 aqueous solution, respectively. Compared with these two cases, the
      electrochemical deposition of silver in BMIMBF4 deviated from both the
      instantaneous and progressive nucleation models, which could be controlled by
      mixed kinetics and diffusion. On the basis of the experimental results, it was
      shown that parameters such as viscosity and water miscibility of RTILs would
      affect the electrodeposition behavior of silver. Atom force microscopy was
      employed to probe the surface morphology of the silver deposit, and it showed
      that the shining electrodeposit of silver was fairly dense and separate
      nanoclusters of <100 nm were in evidence, corresponding to an island growth
      model. The strongly enhanced Raman scattering from the monolayer film of 4
      mercaptobenzoic acid demonstrated that as-prepared silver nanoparticular film was
      surface-enhanced Raman scattering (SERS) active. The enhancement factor was
      calculated to be up to 9.0 x 10(5) and 1.0 x 10(6) for the silver film obtained
      in BMIMPF6 and BMIMBF4 RTILs, respectively.

PMID- 15518523
TI  - Flexible ureasil hybrids with tailored optical properties through doping with
      metal nanoparticles.
AB  - Hybrid organic-inorganic nanocomposites containing uniform distributions of metal
      nanoparticles have been prepared by mixing a preformed nanoparticle colloid with
      the precursors of a ureasil, prior to the sol-gel transition. These
      nanocomposites possess not only high optical quality and optical features
      dictated by the size and shape of the nanoparticle dopants but also a high degree
      of flexibility, which can largely enhance the range of applications in practical
      devices. The deposition of a uniform silica shell on the nanoparticle surface
      prior to the sol-gel transition was found to be required to maintain the
      colloidal stability during the process and, thus, to retain the optical
      properties in the final nanocomposite material. This method can be readily
      extended to other materials, such as semiconductor and magnetic nanoparticles.

PMID- 15518524
TI  - Gold nanoparticle embedded, self-sustained chitosan films as substrates for
      surface-enhanced Raman scattering.
AB  - In this work, self-sustained, biocompatible, biodegradable films containing gold
      nanostructures have been fabricated for potential application in nanobioscience
      and ultrasensitive chemical and biochemical analysis. We report a novel synthesis
      of gold nanoparticles mediated by the biopolymer chitosan. Self-supporting thin
      films are formed from the resultant gold-chitosan nanocomposite solutions and
      characterized by UV-visible surface plasmon absorption, transmission electron
      microscopy, atomic force microscopy, infrared absorption, and Raman scattering
      measurements. Results demonstrate control over the size and distribution of the
      nanoparticles produced, which is promising for several applications, including
      the development of biosensors. As a proof of principle, we demonstrate that gold
      chitosan films can be employed in trace analysis using surface-enhanced Raman
      scattering.

PMID- 15518525
TI  - Surface modification and characterization of magnetic polymer nanospheres
      prepared by miniemulsion polymerization.
AB  - A novel and effective protocol for the surface modification and quantitative
      characterization of magnetic polymeric nanospheres prepared by miniemulsion
      polymerization is reported. Composite nanospheres consisting of polymer-coated
      iron oxide nanoparticles were prepared by the miniemulsion polymerization of
      methyl methacrylate and divinylbenzene in the presence of magnetic fluid. Surface
      modification reaction of the magnetic polymer with poly(ethylene glycol) (PEG)
      was employed to obtain a hydrophilic hydroxyl-group-functionalized magnetic
      nanospheres. An affinity dye, Cibacron blue F3G-A (CB), was then coupled
      covalently to prepare a magnetic nonporous affinity adsorbent. The morphology and
      magnetic property of the polymer nanospheres obtained were examined by
      transmission electron microscopy and a vibrating sample magnetometer. The
      contents of surface groups modified were quantitatively measured by using
      diffusive reflectance Fourier transform infrared spectroscopy on the basis of a
      linear relationship between the intensity ratio of IC-O-C/IC=O and the content of
      PEG. X-ray photoelectron spectroscopy (XPS) was used to examine the surface of
      magnetic nanospheres. It was confirmed by the comparison of XPS spectra of both
      dye-coated and uncoated magnetic nanospheres to which the CB ligand was coupled,
      and the surface of the PEG-modified nanospheres had an exact 3:7 atomic ratio of
      sulfur to nitrogen.

PMID- 15518527
TI  - Influence of the pore structure of MCM-41 and SBA-15 silica fibers on atomic
      layer chemical vapor deposition of cobalt carbonyl.
AB  - Mesoporous high surface area MCM-41 and SBA-15 type silica materials with fibrous
      morphology were synthesized and used as support materials for the ALCVD (atomic
      layer chemical vapor deposition) preparation of Co/MCM-41 and Co/SBA-15
      catalysts. Co/MCM-41 and Co/SBA-15 catalysts were prepared by deposition of
      Co2(CO)8 from the gas phase onto the surfaces of preheated support materials in a
      fluidized bed reactor. For both silica materials, two different kinds of
      preparation methods, direct deposition and a pulse deposition method, were used.
      Pure silica supports as well as supported cobalt catalysts were characterized by
      various spectroscopic (IR) and analytical (X-ray diffraction, Brunauer-Emmett
      Teller, elemental analysis) methods. MCM-41 and SBA-15 fibers showed considerable
      ability to adsorb Co2(CO)8 from the gas phase. For MCM-41 and SBA-15 silicas,
      cobalt loadings of 13.7 and 12.1 wt % were obtained using the direct deposition
      method. The cobalt loadings increased to 23.0 and 20.7 wt % for MCM-41 and SBA-15
      silicas, respectively, when the pulse deposition method was used. The reduction
      behavior of silica-supported cobalt catalysts was found to depend on the catalyst
      preparation method and on the mesoporous structure of the support material.
      Almost identical reduction properties of SBA-15-supported catalysts prepared by
      different deposition methods are explained by the structural properties of the
      mesoporous support and, in particular, by the chemical structure of the inner
      surfaces and walls of the mesopores. Pulse O2/H2 chemisorption experiments showed
      catalytically promising redox properties and surface stability of the prepared
      MCM-41- and SBA-15-supported cobalt catalysts.

PMID- 15518526
TI  - Iron and cobalt oxide and metallic nanoparticles prepared from ferritin.
AB  - Metallic Fe and Co and Fe- and Co-based oxide nanoparticles were prepared by a
      novel method utilizing the biologically relevant protein ferritin. In particular,
      iron and cobalt oxyhydroxide nanoparticles were assembled within horse spleen and
      Listeria innocua derived ferritin, respectively, in the aqueous phase. Ferritin
      containing either Fe or Co oxide was transferred and dried on a SiO2 support
      where the protein shell was removed during exposure to a highly oxidizing
      environment. It was also shown that the metal oxide particles could be reduced to
      the respective metal by heating in hydrogen. X-ray photoelectron spectroscopy was
      used to characterize the composition of the particles and atomic force microscopy
      was used to characterize the size of the nanoparticles. Depending on the Fe or Co
      loading and/or type of ferritin used, metallic and oxide nanoparticles could be
      produced within a range of 20-60 A.

PMID- 15518528
TI  - Synthesis and characterization of nitric oxide-releasing sol-gel microarrays.
AB  - Diazeniumdiolate-modified sol-gel microarrays capable of releasing low levels of
      nitric oxide are reported as a viable means for improving the blood compatibility
      of a surface without fully modifying the underlying substrate. Several parameters
      are characterized including: (1) NO surface flux as a function of sol-gel
      composition and microarray geometry; (2) microstructure dimensions and spacing
      for optimal blood compatibility; and (3) the effect of sol-gel surface
      modification on analyte accessibility to platinum electrodes. The sol-gel
      microarrays release biologically relevant levels of NO under physiological
      conditions for >24 h. In vitro platelet adhesion assays indicate that a NO
      surface flux of 2.2 pmol cm(-2) s(-1) effectively reduces platelet adhesion to
      glass substrates modified with sol-gel microstructures separated by 50 microm.
      The blood compatibility observed for these micropatterned surfaces is comparable
      to NO-releasing sol-gel films. When the separation between NO-releasing
      microstructures is reduced to 10 microm, the NO surface flux required to reduce
      platelet adhesion is lowered to 0.4 pmol cm(-2) s(-1). Finally, the oxygen
      response of platinum electrodes modified with NO-releasing sol-gel microarrays
      indicates that selective modification via micropatterning enhances analyte
      accessibility to the sensor surface.

PMID- 15518529
TI  - Supported particle track etched polyimide membranes: a grazing incidence small
      angle X-ray scattering study.
AB  - Particle track etched polyimide membranes on silicon substrates covered with a
      native oxide layer are investigated. Preparation steps similar to the common
      classical particle track etched membrane production, giving rise to free-standing
      membranes, are successfully applied to the supported membranes. Polyimide films
      are used as a starting material for a template preparation based on high energy
      ion irradiation. The film/membrane structure is probed at different length scales
      by grazing incidence small-angle X-ray scattering at each individual preparation
      step. In addition, characterization with atomic force microscopy, variable-angle
      spectroscopic ellipsometry, Fourier transform infrared transmission, and
      attenuated total reflection spectroscopy is performed. An amount of 6 +/- 1 vol %
      pores inside the polyimide film is detected. The pores are oriented perpendicular
      to the substrate surface and have a conical shape, yielding a slightly reduced
      pore size at the substrate/film interface.

PMID- 15518530
TI  - Time-resolved in situ studies of the formation of cubic mesoporous silica formed
      with triblock copolymers.
AB  - The mechanism of formation of two different cubic mesoporous silica materials
      formed with Pluronic triblock copolymers is investigated with in situ time
      resolved small-angle synchrotron X-ray scattering, in situ time-resolved 1H
      nuclear magnetic resonance, and time-resolved transmission electron microscopy.
      The materials studied are the micellar cubic (Imm) SBA-16 formed with Pluronic
      F108 and the bicontinuous cubic (Iad) silica material formed with Pluronic P103
      and NaI. The formation mechanisms of the two cubic structures are shown to be
      dissimilar. For the Imm material, in the early stages of the synthesis, flocs of
      unordered micelles are observed, but areas where the micelles have started to
      order are also present. With time, there is an increase in order; however, there
      is a coexistence of unordered micelles and ordered material all through this
      study. The bicontinuous cubic silica is formed via a different path. The system
      is phase-separated already before the addition of the silica source, which
      implies that a concentrated phase is present, acting as the structure director of
      the Iad structure. The results are compared with earlier reports on the formation
      of the hexagonal SBA-15 material.

PMID- 15518531
TI  - Interparticle spacing control in the superlattices of carboxylic acid-capped gold
      nanoparticles by hydrogen-bonding mediation.
AB  - We have demonstrated that carboxylic acid-capped gold nanoparticles were self
      assembled to form two-dimensional (2D) and/or three-dimensional (3D)
      superlattices at an air/water interface in the presence of a bifunctional
      hydrogen-bonding mediator such as 4-pyridinecarboxylic acid (PyC) or trans-3-(3
      pyridyl)acrylic acid (PyA). Transmission electron microscopy revealed a hexagonal
      close-packed arrangement of nanoparticles in the superlattice with an extension
      of interparticle spacing. In the 2D superlattices, larger particles produced a
      higher-quality assembly having long-range translational ordering. Attenuated
      total reflectance IR (ATR-IR) spectroscopy revealed the presence of hydrogen
      bonds between the mediator used and the capping agents of carboxylic acid on
      nanoparticle surfaces. Since the experimentally obtained interparticle separation
      distance agreed approximately with that obtained by the geometrical model
      calculations, we conclude that the hydrogen-bonding mediation controlled the
      interparticle spacing or structure by monomolecular incorporation between
      adjacent nanoparticles in the superlattices.

PMID- 15518532
TI  - Electrokinetics of diffuse soft interfaces. 1. Limit of low Donnan potentials.
AB  - The current theoretical approaches to electrokinetics of gels or polyelectrolyte
      layers are based on the assumption that the position of the very interface
      between the aqueous medium and the gel phase is well defined. Within this
      assumption, spatial profiles for the volume fraction of polymer segments (phi),
      the density of fixed charges in the porous layer (rho fix), and the coefficient
      modeling the friction to hydrodynamic flow (k) follow a step-function. In
      reality, the "fuzzy" nature of the charged soft layer is intrinsically
      incompatible with the concept of a sharp interface and therefore necessarily
      calls for more detailed spatial representations for phi, rho fix, and k. In this
      paper, the notion of diffuse interface is introduced. For the sake of
      illustration, linear spatial distributions for phi and rho fix are considered in
      the interfacial zone between the bulk of the porous charged layer and the bulk
      electrolyte solution. The corresponding distribution for k is inferred from the
      Brinkman equation, which for low phi reduces to Stokes' equation. Linear
      electrostatics, hydrodynamics, and electroosmosis issues are analytically solved
      within the context of streaming current and streaming potential of charged
      surface layers in a thin-layer cell. The hydrodynamic analysis clearly
      demonstrates the physical incorrectness of the concept of a discrete slip plane
      for diffuse interfaces. For moderate to low electrolyte concentrations and
      nanoscale spatial transition of phi from zero (bulk electrolyte) to phi o (bulk
      gel), the electrokinetic properties of the soft layer as predicted by the theory
      considerably deviate from those calculated on the basis of the discontinuous
      approximation by Ohshima.

PMID- 15518533
TI  - Pattern formation and dewetting in thin films of liquids showing complete
      macroscale wetting: from "pancakes"to "swiss cheese".
AB  - Based on the complete 3D numerical solutions of the nonlinear thin film equation,
      we address the problems of surface instability, dynamics, morphological diversity
      and evolution in unstable thin films of the liquids that display complete
      macroscale wetting. The twin constraints of complete macroscale wettability and
      nanoscale instability produce a variety of microscopic morphological phases
      approximating sharp crystal surfaces with flat tops resembling a mesa or a micro
      "pancake" or a slice of Swiss cheese. While the maximum thickness of flat regions
      is found to be independent of the initial film thickness, the precise lateral
      morphology of microdomains formed depends on the film thickness. As the film
      thickness is increased, the initial pathway of evolution changes from the
      formation of small spherical droplets, to long mesas (parapets) and islands, to
      circular holes, all of which eventually resolve by ripening into a collection of
      round pancakes at equilibrium. However, beyond a certain transition thickness, a
      novel metastable honeycombed morphology, resembling a membrane or a slice of
      Swiss cheese, is uncovered, which is produced by an abrupt "freezing" of the
      evolution during hole growth. In contrast, the spinodal dewetting in thin films
      of partially wettable systems always engenders spherical droplets at equilibrium.
      The equilibrium dewetted area from simulations, as well as from simple mass
      balance, is shown to decline linearly with the initial film thickness.

PMID- 15518534
TI  - Acoustic second harmonic generation from rough surfaces under shear excitation in
      liquids.
AB  - Emission of compressional acoustic waves at the second harmonic frequency (second
      harmonic generation, SHG) is possible from rough surfaces undergoing oscillatory
      shear in liquids. This nonlinear response is a consequence of the inertial term
      in the Navier-Stokes equation. On a corrugated surface, the streamlines of the
      sheared liquid are not strictly parallel to the surface, leading to variation of
      pressure along the streamlines and a concomitant Bernoulli pressure. Being
      quadratic in speed, the Bernoulli pressure contains a static term and a term at
      the second harmonic frequency, 2omega. Pressure fluctuations at 2omega generate
      compressional waves.

PMID- 15518535
TI  - Diblock polyampholytes grafted onto spherical particles: Monte Carlo simulation
      and lattice mean-field theory.
AB  - Spherical brushes composed of diblock polyampholytes (diblock copolymers with
      oppositely charged blocks) grafted onto solid spherical particles in aqueous
      solution are investigated by using the primitive model solved with Monte Carlo
      simulations and by lattice mean-field theory. Polyampholyte chains of two
      compositions are considered: a copolymer with a long and a short block, A100B10,
      and a copolymer with two blocks of equal length, A50B50. The B block is end
      grafted onto the surface, and its charge is varied, whereas the charge of the A
      block is fixed. Single-chain properties, radial and lateral spatial distributions
      of different types, and structure factors are analyzed. The brush structure
      strongly depends on the charge of the B block. In the limit of an uncharged B
      block, the chains are stretched and form an extended polyelectrolyte brush. In
      the other limit with the charges of the blocks compensating each other, the
      chains are collapsed and form a polyelectrolyte complex surrounding the
      particles. At intermediate charge conditions, a polyelectrolyte brush and a
      polyelectrolyte complex coexist and constitute two substructures of the spherical
      brush. The differences of the brush structures formed by the A100B10 and A50B50
      polyampholytes are also analyzed. Finally, a comparison of the predictions of the
      two theoretical approaches is made.

PMID- 15518536
TI  - Ornithine cyclodeaminase: structure, mechanism of action, and implications for
      the mu-crystallin family.
AB  - Ornithine cyclodeaminase catalyzes the conversion of L-ornithine to L-proline by
      an NAD(+)-dependent hydride transfer reaction that culminates in ammonia
      elimination. Phylogenetic comparisons of amino acid sequences revealed that the
      enzyme belongs to the mu-crystallin protein family whose three-dimensional fold
      has not been reported. Here we describe the crystal structure of ornithine
      cyclodeaminase in complex with NADH, refined to 1.80 A resolution. The enzyme
      consists of a homodimeric fold whose subunits comprise two functional regions:
      (i) a novel substrate-binding domain whose antiparallel beta-strands form a 14
      stranded barrel at the oligomeric interface and (ii) a canonical Rossmann fold
      that interacts with a single dinucleotide positioned for re hydride transfer. The
      adenosyl moiety of the cofactor resides in a solvent-exposed crevice on the
      protein surface and makes contact with a "domain-swapped"-like coil-helix module
      originating from the dyad-related molecule. Diffraction data were also collected
      to 1.60 A resolution on crystals grown in the presence of l-ornithine. The
      structure revealed that the substrate carboxyl group interacts with the side
      chains of Arg45, Lys69, and Arg112. In addition, the ammonia leaving group
      hydrogen bonds to the side chain of Asp228 and the site of hydride transfer is
      3.8 A from C4 of the nicotinamide. The absence of an appropriately positioned
      water suggested that a previously proposed mechanism that calls for hydrolytic
      elimination of the imino intermediate must be reconsidered. A more parsimonious
      description of the chemical mechanism is proposed and discussed in relation to
      the structure and function of mu-crystallins.

PMID- 15518537
TI  - Reconstituting modular activity from separated domains of 6-deoxyerythronolide B
      synthase.
AB  - The hallmark of a type I polyketide synthase (PKS), such as the 6
      deoxyerythronolide B synthase (DEBS), is the presence of catalytic modules
      comprised of covalently fused domains acting together to catalyze one round of
      chain elongation. In addition to an obligate ketosynthase (KS), acyl transferase
      (AT), and acyl carrier protein (ACP), a module may also include a ketoreductase
      (KR), dehydratase (DH), and/or enoyl reductase (ER) domain. The size,
      flexibility, and fixed domain-domain stoichiometry of these PKS modules present
      challenges for structural, mechanistic, and protein-engineering studies. Here, we
      have harnessed the power of limited proteolysis and heterologous protein
      expression to isolate and characterize individual domains of module 3 of DEBS, a
      150-kD protein consisting of a KS, an AT, an ACP, and an inactive KR domain. Two
      interdomain boundaries were identified via limited proteolysis, which led to the
      production of a 90-kD KS-AT, a 142-kD KS-AT-KR(0), and a 10-kD ACP as
      structurally stable stand-alone proteins. Each protein was shown to possess the
      requisite catalytic properties. In the presence of the ACP, both the KS-AT and
      the KS-AT-KR(0) proteins were able to catalyze chain elongation as well as the
      intact parent module. Separation of the KS from the ACP enabled direct
      interrogation of the KS specificity for both the nucleophilic substrate and the
      partner ACP. Malonyl and methylmalonyl extender units were found to be equivalent
      substrates for chain elongation. Whereas ACP2 and ACP4 of DEBS could be exchanged
      for ACP3, ACP6 was a substantially poorer partner for the KS. Remarkably, the
      newly identified proteolytic sites were conserved in many PKS modules, raising
      the prospect of developing improved methods for the construction of hybrid PKS
      modules by engineering domain fusions at these interdomain junctions.

PMID- 15518538
TI  - Investigating the dynamic properties of the transmembrane segment of
      phospholamban incorporated into phospholipid bilayers utilizing 2H and 15N solid
      state NMR spectroscopy.
AB  - (2)H and (15)N solid-state NMR spectroscopic techniques were used to investigate
      the membrane composition, orientation, and side-chain dynamics of the
      transmembrane segment of phospholamban (TM-PLB), a sarcoplasmic Ca(2+)-regulator
      protein. (2)H NMR spectra of (2)H-labeled leucine (deuterated at one terminal
      methyl group) incorporated at different sites (CD(3)-Leu28, CD(3)-Leu39, and
      CD(3)-Leu51) along the TM-PLB peptide exhibited line shapes characteristic of
      either methyl group reorientation about the C(gamma)-C(delta) bond axis or by
      additional librational motion about the C(alpha)-C(beta) and C(beta)-C(gamma)
      bond axes. The (2)H NMR line shapes of all CD(3)-labeled leucines are very
      similar below 0 degrees C, indicating that all of the residues are located inside
      the lipid bilayer. At higher temperatures, all three labeled leucine residues
      undergo rapid reorientation about the C(alpha)-C(beta), C(beta)-C(gamma), and
      C(gamma)-C(delta) bond axes as indicated by (2)H line-shape simulations and
      reduced quadrupolar splittings. At all of the temperatures studied, the (2)H NMR
      spectra indicated that the Leu51 side chain has less motion than Leu39 or Leu28,
      which is attributed to its incorporation in the pentameric PLB leucine zipper
      motif. The (15)N powder spectra of Leu39 and Leu42 residues indicated no backbone
      motion, while Leu28 exhibited slight backbone motion. The chemical-shift
      anisotropy tensor values for (15)N-labeled Leu TM-PLB were sigma(11) = 50.5 ppm,
      sigma(22) = 80.5 ppm, and sigma(33) = 229 ppm within +/-3 ppm experimental error.
      The (15)N chemical-shift value from the mechanically aligned spectrum of (15)N
      labeled Leu39 PLB in DOPC/DOPE phospholipid bilayers was 220 ppm and is
      characteristic of a TM peptide that is nearly parallel with the bilayer normal.

PMID- 15518539
TI  - Why zinc fingers prefer zinc: ligand-field symmetry and the hidden thermodynamics
      of metal ion selectivity.
AB  - The zinc finger, a motif of protein-nucleic acid recognition broadly conserved
      among eukaryotes, is a globular minidomain containing a tetrahedral metal-binding
      site. Preferential coordination of Zn(2+) (relative to Co(2+)) is proposed to
      reflect differences in ligand-field stabilization energies (LFSEs) due to
      complete or incomplete occupancy of d orbitals. LFSE predicts that the preference
      for Zn(2+) should be purely enthalpic in accord with calorimetric studies of a
      high-affinity consensus peptide (CP-1; Blasie, C. A., and Berg, J. (2002)
      Biochemistry 41, 15068-73). Despite its elegance, the general predominance of
      LFSE is unclear as (i) the magnitude by which CP-1 prefers Zn(2+) is greater than
      that expected and (ii) the analogous metal ion selectivity of a zinc
      metalloenzyme (carbonic anhydrase) is driven by changes in entropy rather than
      enthalpy. Because CP-1 was designed to optimize zinc binding, we have
      investigated the NMR structure and metal ion selectivity of a natural finger of
      lower stability derived from human tumor-suppressor protein WT1. Raman
      spectroscopy suggests that the structure of the WT1 domain is unaffected by
      interchange of Zn(2+) and Co(2+). As in CP-1, preferential binding of Zn(2+)
      (relative to Co(2+)) is driven predominantly by differences in enthalpy, but in
      this case the enthalpic advantage is less than that predicted by LFSE. A
      theoretical framework is presented to define the relationship between LFSE and
      other thermodynamic factors, such as metal ion electroaffinities, enthalpies of
      hydration, and the topography of the underlying folding landscape. The
      contribution of environmental coupling to entropy-enthalpy compensation is
      delineated in a formal thermodynamic cycle. Together, these considerations
      indicate that LFSE provides an important but incomplete description of the
      stringency and thermodynamic origin of metal-ion selectivity.

PMID- 15518540
TI  - Atomic mapping of the interactions between the antiviral agent cyanovirin-N and
      oligomannosides by saturation-transfer difference NMR.
AB  - The minimum oligosaccharide structure required for binding to the potent HIV
      inactivating protein cyanovirin-N (CV-N) was determined by saturation-transfer
      difference (STD) NMR spectroscopy. Despite the low molecular mass of the protein
      (11 kDa), STD-NMR spectroscopy allowed the precise atomic mapping of the
      interactions between CV-N and various di- and trimannosides, substructures of Man
      9, the predominant oligosaccharide on the HIV viral surface glycoprotein gp120.
      Contacts with mannosides containing the terminal Manalpha(1-->2)Manalpha unit of
      Man-9 were observed, while (1-->3)- and (1-6)-linked di- and trimannosides showed
      no interactions, demonstrating that the terminal Manalpha(1-->2)Manalpha
      structure plays a key role in the interaction. Precise epitope mapping revealed
      that, for Manalpha(1-->2)ManalphaOMe, Manalpha(1-->2)Manalpha(1-->3)ManalphaOMe,
      and Manalpha(1-->2)Manalpha(1-->6)ManalphaOMe, the protein is in close contact
      with H2, H3, and H4 of the nonreducing terminal mannose unit. In contrast, the
      STD-NMR spectrum of the CV-N/trisaccharide Manalpha(1-->2)Manalpha(1-
      >2)ManalphaOMe complex was markedly different, with resonances on all sugar units
      displaying equal enhancements, suggesting that CV-N is able to discriminate
      between the three structurally related trisaccharides.

PMID- 15518541
TI  - Hydrophobic core around tyrosine for human endothelin-1 investigated by
      photochemically induced dynamic nuclear polarization nuclear magnetic resonance
      and matrix-assisted laser desorption ionization time-of-flight mass spectrometry.
AB  - Human endothelin-1 (ET-1) is a potent cardiovascular bioactive peptide. Its
      activity is based on the C-terminal residues, e.g., Trp 21 in particular.
      Recently, we reported an NMR solution structure of ET-1, which has a C-terminal
      hydrophobic core around Tyr 13. This C-terminal conformation does not agree with
      a previously reported X-ray crystal structure. To clarify the discrepancy, we
      performed photo-CIDNP NMR in combination with MALDI-TOF MS. The photo-CIDNP
      results revealed that the Tyr 13 aromatic ring is concealed in a hydrophobic
      interaction. MALDI-TOF MS experiments showed this is an intramolecular
      interaction in monomeric form, which is also supported by sedimentation analysis
      and two-dimensional NMR cross-peak line shapes. Thus, we confirmed the
      intramolecular hydrophobic core around Tyr 13 in aqueous solution, which agrees
      with the solution structure. The C-terminal conformational discrepancy between
      the solution and crystal was caused by the intermolecular hydrogen bond between
      Tyr 13 of one molecule and Asp 8 of the other in a dimer-like formation of
      crystalline ET-1. On the other hand, we indicated that endothelin-3, another
      isoform of the endothelin, has an apparent self-association equilibrium under the
      same condition in which three tyrosines participate.

PMID- 15518542
TI  - NMR structures of salt-refolded forms of the 434-repressor DNA-binding domain in
      6 M urea.
AB  - The N-terminal 63-residue fragment of the phage 434-repressor, 434(1-63), has a
      well-defined globular fold in H(2)O solution, and is unfolded in 6 M urea at pH
      7.5. In this study, 434(1-63) has been refolded by adding either 1.7 M NaCl or
      0.47 M NaTFA to the solution in 6 M urea, and the NMR structures of both refolded
      forms have been determined. The two refolded forms have similar free energies of
      unfolding and are approximately 16 kJ/mol less stable than the protein in H(2)O
      solution. 434(1-63) refolded with NaCl exhibits NMR chemical shifts very similar
      to and a three-dimensional structure nearly identical to those of 434(1-63) in
      H(2)O solution. The protein refolded with NaTFA also has a similar global fold,
      but it shows local differences near Phe44, of which two different orientations of
      the aromatic ring are compatible with the experimental data. This local
      conformational polymorphism attracted our interest because hydrophobic contacts
      between two subdomains of residues 1-36 and 45-63 are mediated by the Phe44 side
      chain. Anion binding experiments suggest that this polymorphism is caused by
      binding of TFA(-) anions to a cluster of positively charged Arg and Lys residues
      located in the loop connecting the two subdomains, with apparent binding
      constants for TFA(-) (K(app)) on the order of 30 mM(-1).

PMID- 15518543
TI  - Tumor cells resistant to a microtubule-depolymerizing hemiasterlin analogue, HTI
      286, have mutations in alpha- or beta-tubulin and increased microtubule
      stability.
AB  - Hemiasterlins are sponge-derived tripeptides that inhibit cell growth by
      depolymerizing existing microtubules and inhibiting microtubule assembly. Since
      hemiasterlins are poor substrates for P-glycoprotein, they are attractive
      candidates for cancer therapy and have been undergoing clinical trials. The basis
      of resistance to a synthetic analogue of hemiasterlin, HTI-286 (HTI), was
      examined in cell populations derived from ovarian carcinoma (A2780/1A9) cells
      selected in HTI-286. 1A9-HTI-resistant cells (1A9-HTI(R) series) were 57-89-fold
      resistant to HTI. Cross-resistance (3-186-fold) was observed to other tubulin
      depolymerizing drugs, with collateral sensitivity (2-14-fold) to tubulin
      polymerizing agents. Evaluation of the percentage of polymerized and soluble
      tubulin in 1A9 parental and 1A9-HTI(R) cells corroborated the HTI cytotoxicity
      data. At 22 degrees C or 37 degrees C, in the absence of any drug, the percentage
      of polymerized microtubules for each of the 1A9-HTI(R) populations was greater
      than that in the 1A9 parental cells, consistent with more stable microtubules.
      Furthermore, microtubules in the 1A9-HTI(R) populations were also more resistant
      to depolymerization at 4 degrees C and had more acetylated and detyrosinated (Glu
      tubulin) alpha-tubulin, all characteristic of more stable microtubules. The 1A9
      HTI(R) cell populations exhibited either a single nucleotide change in the M40
      beta-tubulin isotype, S172A, or in two cell populations where no beta-tubulin
      mutation was detected, mutations in the Kalpha-1 alpha-tubulin isotype, S165P and
      R221H in one resistant cell population and I384V in another. Unlike reports of
      mutations resulting in reduced drug affinity, the experimental data and location
      of mutations are consistent with resistance to HTI-286 mediated by microtubule
      stabilizing mutations in beta- or alpha-tubulin.

PMID- 15518544
TI  - Localization of the antimitotic peptide and depsipeptide binding site on beta
      tubulin.
AB  - Several naturally occurring peptides and depsipeptides which include the
      cryptophycins, dolastatin 10, hemiasterlin, and phomopsin A have been found to be
      potent antimitotic agents, causing cell death at picomolar or low nanomolar
      concentrations. These compounds inhibit microtubule growth, modulate the dynamics
      of microtubules, and induce the self-association of tubulin dimers into single
      walled rings and spirals. These peptides exhibit mutual competitive inhibition in
      binding to beta-tubulin, while noncompetitively inhibiting the binding of
      vinblastine and vincristine to beta-tubulin. Despite the abundance of biochemical
      information, the details of their molecular interactions with tubulin are not
      known. In this study, using a combination of molecular dynamics simulations and
      molecular docking studies, a common binding site for cryptophycin 1, cryptophycin
      52, dolastatin 10, hemiasterlin, and phomopsin A on beta-tubulin has been
      identified. Application of these same methods to alpha-tubulin indicated no
      interaction between alpha-tubulin and any of the peptides. On the basis of the
      docking results, a model for the mechanism of microtubule disruption and
      formation of aberrant nonmicrotubule structures is proposed. Both the active site
      and mechanism of microtubule depolymerization predictions are in good agreement
      with experimental findings.

PMID- 15518545
TI  - Biochemical and biophysical characterization of serotonin 5-HT2C receptor
      homodimers on the plasma membrane of living cells.
AB  - While many studies have provided evidence of homodimerization and
      heterodimerization of G-protein-coupled receptors (GPCRs), few studies have used
      fluorescence resonance energy transfer (FRET) combined with confocal microscopy
      to visualize receptor dimerization on the plasma membrane, and there have been no
      reports demonstrating the expression of serotonin receptor dimers/oligomers on
      the plasma membrane of living cells. In the study presented here, biochemical and
      biophysical techniques were used to determine if 5-HT(2C) receptors exist as
      homodimers on the plasma membrane of living cells. Immunoprecipitation followed
      by Western blotting revealed the presence of immunoreactive bands the predicted
      size of 5-HT(2C) receptor monomers and homodimers that were detergent and cross
      linker sensitive. Bioluminescence resonance energy transfer (BRET) was assessed
      in HEK293 cells expressing 5-HT(2C) receptors labeled with Renilla luciferase and
      yellow fluorescent protein. BRET levels were not altered by pretreatment with
      serotonin. Confocal microscopy provided direct visualization of FRET on the
      plasma membrane of live cells expressing 5-HT(2C) receptors labeled with cyan
      (donor) and yellow (acceptor) fluorescent proteins. FRET, assessed by acceptor
      photobleaching, was dependent on the donor/acceptor ratio and independent of
      acceptor expression levels, indicating that FRET resulted from receptor
      clustering and not from overexpression of randomly distributed receptors,
      providing evidence for GPCR dimers/oligomers in a clustered distribution on the
      plasma membrane. The results of this study suggest that 5-HT(2C) receptors exist
      as constitutive homodimers on the plasma membrane of living cells. In addition, a
      confocal-based FRET method for monitoring receptor dimerization directly on the
      plasma membrane of living cells is described.

PMID- 15518546
TI  - Membrane assembly of M13 major coat protein: evidence for a structural adaptation
      in the hinge region and a tilted transmembrane domain.
AB  - New insights into the low-resolution structure of the hinge region and the
      transmembrane domain of the membrane-bound major coat protein of the
      bacteriophage M13 are deduced from a single cysteine-scanning approach using
      fluorescence spectroscopy. New mutant coat proteins are labeled and reconstituted
      into phospholipid bilayers with varying headgroup compositions (PC, PE, and PG)
      and thicknesses (14:1PC, 18:1PC, and 22:1PC). Information about the polarity of
      the local environment around the labeled sites is deduced from the wavelength of
      maximum emission using AEDANS attached to the SH groups of the cysteines as a
      fluorescent probe. It is found that the protein is almost entirely embedded in
      the membrane, whereas the phospholipid headgroup composition of the membrane
      hardly affects the overall embedment of the protein in the membrane. From the
      assessment of a hydrophobic and hydrophilic face of the transmembrane helix, it
      is concluded that the helix is tilted with respect to the membrane normal. As
      compared to the thicker 18:1PC and 22:1PC membranes, reconstitution of the
      protein in the thin 14:1PC membranes results in a loss of helical structure and
      in the formation of a stretched conformation of the hinge region. It is suggested
      that the hinge region acts as a flexible spring between the N-terminal
      amphipathic arm and transmembrane hydrophobic helix. On average, the membrane
      bound state of the coat protein can be seen as a gently curved and tilted,
      "banana-shaped" molecule, which is strongly anchored in the membrane-water
      interface at the C-terminus. From our experiments, we propose a rather small
      conformational adaptation of the major coat protein as the most likely reversible
      mechanism for responding to environmental changes during the bacteriophage
      disassembly and assembly process.

PMID- 15518547
TI  - Divergence of function in the thioredoxin fold suprafamily: evidence for
      evolution of peroxiredoxins from a thioredoxin-like ancestor.
AB  - The thioredoxin fold is found in proteins that serve a wide variety of functions.
      Among these are peroxiredoxins, which catalyze the reduction of hydrogen peroxide
      and alkyl peroxides. Although the common structural fold shared by thioredoxins
      and peroxiredoxins suggests the possibility that they have evolved from a common
      progenitor, it has been difficult to examine this hypothesis in depth because
      pairwise sequence identities between proteins in these two superfamilies are
      statistically insignificant. Using the Shotgun program, we have found that
      sequences of reductases involved in maturation of cytochromes in certain bacteria
      bridge the sequences of thioredoxins and peroxiredoxins. Analysis of motifs found
      in a divergent set of thioredoxins, cytochrome maturation proteins, and
      peroxiredoxins provides further support for an evolutionary relationship between
      these proteins. Within the conserved motifs are specific residues that are
      characteristic of individual protein classes, and therefore are likely to be
      involved in the specific functions of those classes. We have used this
      information, in combination with existing structural and functional information,
      to gain new insight into the structure-function relationships in these proteins
      and to construct a model for the emergence of peroxiredoxins from a thioredoxin
      like ancestor.

PMID- 15518548
TI  - Crystal structure of CaiB, a type-III CoA transferase in carnitine metabolism.
AB  - Carnitine is an important molecule in human metabolism, mainly because of its
      role in the transport of long-chain fatty acids across the inner mitochondrial
      membrane. Escherichia coli uses carnitine as a terminal electron acceptor during
      anaerobic metabolism. Bacteria present in our large intestine break down
      carnitine that is not absorbed in the small intestine. One part of this catabolic
      pathway is reversible and can be utilized for bioproduction of large amounts of
      stereochemically pure L-carnitine, which is used medically for the treatment of a
      variety of human diseases. Here, we present the crystal structure of the E. coli
      protein CaiB, which is a member of the recently identified type-III coenzyme A
      (CoA) transferase family and catalyzes the transfer of the CoA moiety between
      gamma-butyrobetaine-CoA and carnitine forming carnityl-CoA and gamma
      butyrobetaine. This is the first protein from the carnitine metabolic pathway to
      be structurally characterized. The structure of CaiB reveals a spectacular fold
      where two monomers are interlaced to form an interlocked dimer. A molecule of the
      crystallization buffer bis-(2-hydroxyethyl)imino-tris(hydroxymethyl)methane (bis
      tris) is bound in a large pocket located primarily in the small domain, and we
      propose that this pocket constitutes the binding site for both substrate moieties
      participating in the CaiB transfer reaction. The binding of CoA to CaiB induces a
      domain movement that closes the active site of the protein. This is the first
      observation of a domain movement in the type-III CoA transferase family and can
      play an important role in coupling substrate binding to initiation of the
      catalytic reaction.

PMID- 15518549
TI  - Folding thermodynamics and kinetics of YNMG RNA hairpins: specific incorporation
      of 8-bromoguanosine leads to stabilization by enhancement of the folding rate.
AB  - Modified nucleotides allow fundamental energetic and kinetic properties of
      nucleic acids to be probed. Here, we demonstrate that an RNA hairpin containing
      the nucleotide analogue 8-bromoguanosine (8BrG or G), gcUUCGgc, has enhanced
      stability relative to the unmodified hairpin, with DeltaDeltaG(37)(degrees)= 
      0.69 +/- 0.15 kcal mol(-1) and DeltaT(M) = +6.8 +/- 1.4 degrees C. NMR
      spectroscopic data suggest that the enhanced stability of gcUUCGgc does not arise
      from the native state; laser temperature-jump experiments support this notion, as
      gcUUCGgc and gcUUCGgc have similar unfolding rate constants, but the folding rate
      constant of gcUUCGgc is 4.1-fold faster at 37.5 degrees C and 2.8-fold faster
      under isoenergetic conditions. On the basis of these findings, we propose that
      8BrG reduces the conformational entropy of the denatured state, resulting in an
      accelerated conformational search for the native state and enhanced stability.

PMID- 15518550
TI  - Metal-dependent DNA cleavage mechanism of the I-CreI LAGLIDADG homing
      endonuclease.
AB  - The LAGLIDADG homing endonucleases include free-standing homodimers,
      pseudosymmetric monomers, and related enzyme domains embedded within inteins. DNA
      bound structures of homodimeric I-CreI and monomeric I-SceI indicate that three
      catalytic divalent metal ions are distributed across a pair of overlapping active
      sites, with one shared metal participating in both strand cleavage reactions.
      These structures differ in the precise position and binding interactions of the
      metals. We have studied the metal dependence for the I-CreI homodimer using site
      directed mutagenesis of active site residues and assays of binding affinity and
      cleavage activity. We have also reassessed the binding of a nonactivating metal
      ion (calcium) in the wild-type enzyme-substrate complex, and determined the DNA
      bound structure of two inactive enzyme mutants. The conclusion of these studies
      is that the catalytic mechanism of symmetric LAGLIDADG homing endonucleases, and
      probably many of their monomeric cousins, involves a canonical two-metal
      mechanism in each of two active sites, which are chemically and structurally
      tethered to one another by a shared metal ion. Failure to occupy the shared metal
      site, as observed in the presence of calcium or when the metal-binding side chain
      from the LAGLIDADG motif (Asp 20) is mutated to asparagine, prevents cleavage by
      the enzyme.

PMID- 15518551
TI  - Crystal structure of the beta-subunit of acyl-CoA carboxylase: structure-based
      engineering of substrate specificity.
AB  - Acetyl-CoA carboxylase (ACC) and propionyl-CoA carboxylase (PCC) catalyze the
      carboxylation of acetyl- and propionyl-CoA to generate malonyl- and methylmalonyl
      CoA, respectively. Understanding the substrate specificity of ACC and PCC will
      (1) help in the development of novel structure-based inhibitors that are
      potential therapeutics against obesity, cancer, and infectious disease and (2)
      facilitate bioengineering to provide novel extender units for polyketide
      biosynthesis. ACC and PCC in Streptomyces coelicolor are multisubunit complexes.
      The core catalytic beta-subunits, PccB and AccB, are 360 kDa homohexamers,
      catalyzing the transcarboxylation between biotin and acyl-CoAs. Apo and substrate
      bound crystal structures of PccB hexamers were determined to 2.0-2.8 A. The
      hexamer assembly forms a ring-shaped complex. The hydrophobic, highly conserved
      biotin-binding pocket was identified for the first time. Biotin and propionyl-CoA
      bind perpendicular to each other in the active site, where two oxyanion holes
      were identified. N1 of biotin is proposed to be the active site base. Structure
      based mutagenesis at a single residue of PccB and AccB allowed interconversion of
      the substrate specificity of ACC and PCC. The di-domain, dimeric interaction is
      crucial for enzyme catalysis, stability, and substrate specificity; these
      features are also highly conserved among biotin-dependent carboxyltransferases.
      Our findings enable bioengineering of the acyl-CoA carboxylase (ACCase) substrate
      specificity to provide novel extender units for the combinatorial biosynthesis of
      polyketides.

PMID- 15518552
TI  - Amino-terminal residues 1-45 of the Escherichia coli pyruvate dehydrogenase
      complex E1 subunit interact with the E2 subunit and are required for activity of
      the complex but not for reductive acetylation of the E2 subunit.
AB  - While N-terminal amino acids 1-55 are not seen in the structure of the
      Escherichia coli pyruvate dehydrogenase complex E1 subunit (PDHc-E1), mass
      spectrometric analysis indicated that this amino-terminal region of PDHc-E1 was
      protected by PDHc-E2. Hence, five deletion constructs of PDHc-E1 were created,
      Delta6-15, Delta16-25, Delta26-35, Delta36-45, and Delta46-55, along with single
      site substitutions at Asp7, Asp9, Pro10, Ile11, Glu12, Thr13, Arg14, and Asp15.
      The decarboxylation of pyruvate and the ability of PDHc-E1 to dimerize are not
      affected by any of the deletions or substitutions. While Delta46-55 and the
      Pro10Ala, Ile11Ala, and Thr13Ala variants could form a complex with PDHc-E2, and
      produced NADH in the overall assay, Delta16-25, Delta26-35, and Delta36-45 and
      the Asp7Ala, Asp9Ala, Glu12Gln, Glu12Asp, Arg14Ala, and Asp15Ala variants failed
      in both respects. Remarkably, all constructs of PDHc-E1 from E. coli, as well as
      PDHc-E1 from Mycobacterium tuberculosis, could carry out reductive acetylation of
      the E. coli lipoyl domain, but only constructs of the E. coli PDHc-E1 could
      reductively acetylate E. coli PDHc-E2. It was concluded that there are at least
      two loci of interaction between the PDHc-E1 and PDHc-E2 subunits: (1) the thiamin
      diphosphate-bound substrate on PDHc-E1 and the lipoylamide of PDHc-E2, as
      reflected by the ability to reductively acetylate the latter; and (2) amino
      terminal residues 1-45 of PDHc-E1 with regions of PDHc-E2 (so far undefined for
      the E. coli complex), as reflected by the overall activity of the entire complex.
      These studies add important information regarding recognition within this
      multienzyme complex class with an alpha(2) E1 assembly.

PMID- 15518553
TI  - Biochemical and crystallographic analyses of maltohexaose-producing amylase from
      alkalophilic Bacillus sp. 707.
AB  - Maltohexaose-producing amylase, called G6-amylase (EC 3.2.1.98), from
      alkalophilic Bacillus sp.707 predominantly produces maltohexaose (G6) from starch
      and related alpha-1,4-glucans. To elucidate the reaction mechanism of G6-amylase,
      the enzyme activities were evaluated and crystal structures were determined for
      the native enzyme and its complex with pseudo-maltononaose at 2.1 and 1.9 A
      resolutions, respectively. The optimal condition for starch-degrading reaction
      activity was found at 45 degrees C and pH 8.8, and the enzyme produced G6 in a
      yield of more than 30% of the total products from short-chain amylose (DP = 17).
      The crystal structures revealed that Asp236 is a nucleophilic catalyst and Glu266
      is a proton donor/acceptor. Pseudo-maltononaose occupies subsites -6 to +3 and
      induces the conformational change of Glu266 and Asp333 to form a salt linkage
      with the N-glycosidic amino group and a hydrogen bond with secondary hydroxyl
      groups of the cyclitol residue bound to subsite -1, respectively. The indole
      moiety of Trp140 is stacked on the cyclitol and 4-amino-6-deoxyglucose residues
      located at subsites -6 and -5 within a 4 A distance. Such a face-to-face short
      contact may regulate the disposition of the glucosyl residue at subsite -6 and
      would govern the product specificity for G6 production.

PMID- 15518554
TI  - Mechanistic crystallography. Mechanism of inactivation of gamma-aminobutyric acid
      aminotransferase by (1R,3S,4S)-3-amino-4-fluorocyclopentane-1-carboxylic acid as
      elucidated by crystallography.
AB  - (1R,3S,4S)-3-Amino-4-fluorocyclopentane-1-carboxylic acid (7) was previously
      shown to be a mechanism-based inactivator of gamma-aminobutyric acid
      aminotransferase (GABA-AT) [Qiu, J. and Silverman, R. B. (2000) J. Med. Chem. 43,
      706-720]. Two mechanisms were considered as reasonable possibilities, a Michael
      addition mechanism and an enamine mechanism. On the basis of a variety of
      chemical studies, including tedious radiolabeling experiments, it was concluded
      that inactivation by 7 proceeds by a Michael addition mechanism. Here, a crystal
      structure of 7 bound to pig liver GABA-AT is reported, which clearly demonstrates
      that the adduct formed is derived from an enamine mechanism. This represents
      another example of how crystallography is an important tool for elucidation of
      inactivation mechanisms.

PMID- 15518555
TI  - Characterization of the heptad repeat regions, HR1 and HR2, and design of a
      fusion core structure model of the spike protein from severe acute respiratory
      syndrome (SARS) coronavirus.
AB  - Severe acute respiratory syndrome coronavirus (SARS-CoV) is a newly emergent
      virus responsible for a worldwide epidemic in 2003. The coronavirus spike
      proteins belong to class I fusion proteins, and are characterized by the
      existence of two heptad repeat (HR) regions, HR1 and HR2. The HR1 region in
      coronaviruses is predicted to be considerably longer than that in other type I
      virus fusion proteins. Therefore the exact binding sequence to HR2 from the HR1
      is not clear. In this study, we defined the region of HR1 that binds to HR2 by a
      series of biochemical and biophysical measures. Subsequently the defined HR1 (902
      952) and HR2 (1145-1184) chains, which are different from previously defined
      binding regions, were linked together by a flexible linker to form a single-chain
      construct, 2-Helix. This protein was expressed in Escherichia coli and forms a
      typical six-helix coiled coil bundle. Highly conserved HR regions between mouse
      hepatitis virus (MHV) and SARS-CoV spike proteins suggest a similar three
      dimensional structure for the two fusion cores. Here, we constructed a homology
      model for SARS coronavirus fusion core based on our biochemical analysis and
      determined the MHV fusion core structure. We also propose an important target
      site for fusion inhibitor design and several strategies, which have been
      successfully used in fusion inhibitor design for human immunodeficiency virus
      (HIV), for the treatment of SARS infection.

PMID- 15518556
TI  - Crystal structure of chicken liver basic fatty acid-binding protein complexed
      with cholic acid.
AB  - Two paralogous groups of liver fatty acid-binding proteins (FABPs) have been
      described: the mammalian type liver FABPs and the basic type (Lb-FABPs)
      characterized in several vertebrates but not in mammals. The two groups have
      similar sequences and share a highly conserved three-dimensional structure, but
      their specificity and stoichiometry of binding are different. The crystal
      structure of chicken Lb-FABP complexed with cholic acid and that of the
      apoprotein refined to 2.0 A resolution are presented in this paper. The two forms
      of the protein crystallize in different space groups, and significant changes are
      observed between the two conformations. The holoprotein binds two molecules of
      cholate in the interior cavity, and the contacts observed between the two ligands
      can help to explain the reason for this stoichiometry of binding. Most of the
      amino acids involved in ligand binding are conserved in other members of the Lb
      FABP family. Since the amino acid sequence of the Lb-FABPs is more similar to
      that of the bile acid-binding proteins than to that of the L-FABPs, the
      possibility that the Lb-FABPs might be more appropriately called liver bile acid
      binding proteins (L-BABPs) is suggested.

PMID- 15518557
TI  - Transition to a beta-sheet-rich structure in spidroin in vitro: the effects of pH
      and cations.
AB  - Unlike man-made fibers, the silks of spiders are spun from aqueous solutions and
      at atmospheric pressure in a process still poorly understood. The molecular
      mechanism of this process involves the conversion of a highly concentrated,
      predominantly disordered silk protein (spidroin) into beta-sheet-rich structures.
      To help store and transport the spidroins in solution, as well as probably
      control their conversion, a liquid crystalline arrangement is established in the
      storage region in the ampulla and persists into the duct. Although it has been
      suggested that changes in the concentration of hydrogen and metal ions play a
      role in the formation of the solid thread, there is no reported evidence that
      these ions influence the secondary structure of native spidroin in solution.
      Here, we demonstrate that pH values between approximately 3.5 and 4.5 induce a
      slow change of conformation from the disordered to the beta-sheet-rich form. We
      also report that Al(3+), K(+), and Na(+) ions induce similar changes in
      structure, while Ca(2+) and Mg(2+) stabilize the predominantly disorder state of
      the protein. Cs(+) and Li(+) have no apparent effect. Direct volumetric and
      spectrophotometric titration showed a pI of 4.22 +/- 0.33 and apparent pK values
      of 6.74 +/- 0.71 and 9.21 +/- 0.27, suggesting a mechanism for the effect of low
      pH on the protein and a rationale for the observed reduction in pH in the duct.
      We discuss the importance of these findings for the spinning process and the
      active role played by the spider to alter the kinetics of the transition.

PMID- 15518558
TI  - Structural basis for phosphomannose isomerase activity in phosphoglucose
      isomerase from Pyrobaculum aerophilum: a subtle difference between distantly
      related enzymes.
AB  - The crystal structure of a dual-specificity phosphoglucose/phosphomannose
      isomerase from the crenarchaeon Pyrobaculum aerophilum (PaPGI/PMI) has been
      determined in complex with glucose 6-phosphate at 1.16 A resolution and with
      fructose 6-phosphate at 1.5 A resolution. Subsequent modeling of mannose 6
      phosphate (M6P) into the active site of the enzyme shows that the PMI activity of
      this enzyme may be due to the additional space imparted by a threonine. In PGIs
      from bacterial and eukaryotic sources, which cannot use M6P as a substrate, the
      equivalent residue is a glutamine. The increased space may permit rotation of the
      C2-C3 bond in M6P to facilitate abstraction of a proton from C2 by Glu203 and,
      after a further C2-C3 rotation of the resulting cis-enediolate, re-donation of a
      proton to C1 by the same residue. A proline residue (in place of a glycine in
      PGI) may also promote PMI activity by positioning the C1-O1 region of M6P. Thus,
      the PMI reaction in PaPGI/PMI probably uses a cis-enediol mechanism of catalysis,
      and this activity appears to arise from a subtle difference in the architecture
      of the enzyme, compared to bacterial and eukaryotic PGIs.

PMID- 15518559
TI  - Prevention of beta strand movement into a zymogen-like position does not confer
      higher activity to coagulation factor VIIa.
AB  - Coagulation factor VIIa (FVIIa) belongs to the chymotrypsin family of S1
      peptidases, whose members require the cleavage of at least one internal peptide
      bond to attain an active conformation. FVIIa also requires association with
      tissue factor (TF) to attain full catalytic competency. Without this, FVIIa has
      very low activity toward peptide and physiologic substrates. Reregistration of
      beta strands has been suggested to play a part in the activation of FVII, and
      their positioning is possibly important for the active conformation of FVIIa. To
      scrutinize this hypothesis, we have designed FVIIa variants which prevent beta
      strand movement and lock FVIIa in the alleged active conformation. The V299M
      mutation, alone or combined with the L280I mutation, was introduced to alter the
      first of two Leu-X-Val motifs in beta strand B2 and thereby prevent
      reregistration. Along the same line, C164V/V299C-FVIIa has a new disulfide which
      would keep beta strand B2 in the registration of active FVIIa. The amidolytic and
      proteolytic activities of V299M-, L280I/V299M-, and C164V/V299C-FVIIa were
      indistinguishable from or lower than those of wild-type FVIIa, and none of the
      mutants displayed an altered exposure of the N-terminal amino group of the
      protease domain. Moreover, the affinities of mutant and native FVIIa for TF
      increased to a similar extent upon incorporation of an active site inhibitor, and
      the enzymatic activities were equally stimulated by TF. In conclusion, we found
      no evidence that the mutants were in a more active state than native FVIIa. Thus,
      the proposed beta strand reregistration, if part of the regulatory mechanism
      governing FVIIa activity, apparently does not suffice for the transformation of
      FVIIa into an enzymatically active conformation. Our data raise the possibility
      that the structural differences between enzymatically latent (zymogen-like) and
      active FVIIa resemble those between trypsinogen and trypsin.

PMID- 15518560
TI  - Disentangling the web of allosteric communication in a homotetramer: heterotropic
      activation in phosphofructokinase from Escherichia coli.
AB  - Phosphofructokinase from Escherichia coli (EcPFK) is a homotetramer with four
      active sites and four allosteric sites. Understanding the allosteric activation
      of EcPFK by MgADP has been complicated by the complex web of possible
      interactions, including active site homotropic interactions, allosteric site
      homotropic interactions, and heterotropic interactions between active and
      allosteric sites. The current work has simplified this web of possible
      interactions to a series of single heterotropic interactions by forming and
      isolating hybrid tetramers. Each of the four unique heterotropic interactions
      have independently been isolated and compared to a control that has all four of
      the unique heterotropic interactions. If the interactions are labeled with the
      distances between interacting ligands, the 45-A interaction contributes 20% +/-
      1%, the 33-A interaction contributes 34% +/- 1%, the 30-A interaction contributes
      21% +/- 1%, and the 23-A interaction contributes 25% +/- 1% with respect to the
      total free energy of MgADP/fructose 6-phosphate (Fru-6-P) activation in the
      control. The free energies of the isolated interactions sum to 100% +/- 2% of the
      total. Therefore, the four unique interactions are all contributors to
      activation, are nonequivalent, and are additive.

PMID- 15518561
TI  - Inhibitor-resistant class A beta-lactamases: consequences of the Ser130-to-Gly
      mutation seen in Apo and tazobactam structures of the SHV-1 variant.
AB  - A bacterial response to the clinical use of class A beta-lactamase inhibitors
      such as tazobactam and clavulanic acid is the expression of variant beta
      lactamases with weaker binding affinities for these mechanism-based inhibitors.
      Some of these inhibitor-resistant variants contain a glycine mutation at Ser130,
      a conserved active site residue known to be adventitiously involved in the
      inhibition mechanism. The crystallographic structure of a complex of tazobactam
      with the Ser130Gly variant of the class A SHV-1 beta-lactamase has been
      determined to 1.8 A resolution. Two reaction intermediates are observed. The
      primary intermediate is an acyclic species bound to the reactive Ser70. It is
      poorly primed for catalytic hydrolysis because its ester carbonyl group is
      completely displaced from the enzyme's oxyanion hole. A smaller fraction of the
      enzyme contains a Ser70-bound aldehyde resulting from hydrolytic loss of the
      triazoyl-sulfinyl amino acid moiety from the primary species. This first
      structure of a class A beta-lactamase lacking Ser130, the side chain of which
      functions in beta-lactam binding and possibly in catalysis, gives
      crystallographic evidence that the acylation step of beta-lactam turnover can
      occur without Ser130. Unexpectedly, the crystal structure of the uncomplexed
      Ser130Gly enzyme, also determined to 1.8 A resolution, shows that a critical
      Glu166-activated water molecule is missing from the catalytic site. Comparison of
      this uncomplexed variant with the wild-type structure reveals that Ser130 is
      required for orienting the side chain of Ser70 and ensuring the hydrogen bonding
      of Ser70 to both Lys73 and the catalytic water molecule.

PMID- 15518562
TI  - NO binding and dynamics in reduced heme-copper oxidases aa3 from Paracoccus
      denitrificans and ba3 from Thermus thermophilus.
AB  - Cytochrome c oxidase (CcO) has a high affinity for nitric oxide (NO), a property
      involved in the regulation of respiration. It has been shown that the
      recombination kinetics of photolyzed NO with reduced CcO from Paracoccus
      denitrificans on the picosecond time scale depend strongly on the NO/enzyme
      stoichiometry and inferred that more than one NO can be accommodated by the
      active site, already at mildly suprastoichiometric NO concentrations. We have
      largely extended these studies by monitoring rebinding dynamics from the
      picosecond to the microsecond time scale, by performing parallel steady-state low
      temperature electron paramagnetic resonance (EPR) characterizations on samples
      prepared similarly as for the optical experiments and comparing them with
      molecular-modeling results. A comparative study was performed on CcO ba(3) from
      Thermus thermophilus, where two NO molecules cannot be copresent in the active
      site in the steady state because of its NO reductase activity. The kinetic
      results allow discrimination between different models of NO-dependent
      recombination and show that the overall NO escape probability out of the protein
      is high when only one NO is bound to CcO aa(3), whereas strong rebinding on the
      15-ns time scale was observed for CcO ba(3). The EPR characterizations show
      similar results for aa(3) at substoichiometric NO/enzyme ratios and for ba(3),
      indicating formation of a 6-coordinate heme-NO complex. The presence of a second
      NO molecule in the aa(3) active site strongly modifies the heme-NO EPR spectrum
      and can be rationalized by a rotation of the Fe-N-O plane with respect to the
      histidine that coordinates the heme iron. This proposal is supported by molecular
      modeling studies that indicate a approximately 63 degrees rotation of heme-bound
      NO upon binding of a second NO to the close-lying copper center CuB. It is argued
      that the second NO binds to CuB.

PMID- 15518563
TI  - Crystal structure of archaeal ribonuclease P protein aRpp29 from Archaeoglobus
      fulgidus.
AB  - The crystal structure of ribonuclease P protein aRpp29 from the sulfate-reducing
      hyperthermophile Archaeoglobus fulgidus was determined at 1.7 A resolution using
      X-ray diffraction methods. The central feature of this archaeal protein is a
      sheet of six antiparallel beta-strands twisted around a conserved hydrophobic
      core. Residues near the N- and C-termini form helical structures that are
      oriented in an antiparallel manner. A comparison of conserved amino acids
      indicates that archaeal aRpp29 is homologous to human ribonuclease P protein
      Rpp29. The aRpp29 protein is structurally similar to bacterial transcription
      factors Hfq and NusG, as well as the Sm and Sm-like RNA-associated proteins from
      eukarya. The crystal structure of A. fulgidus aRpp29 differs from the previously
      reported solution structure, where NMR data did not detect the helices and
      indicated that approximately 40% of the residues are relatively flexible or
      disordered. Circular dichroism data indicate that the protein has less helical
      content than the amount observed in the crystal, suggesting that in solution the
      helical regions are unfolded or in equilibrium between folded and unfolded forms;
      this hypothesis is consistent with amide proton exchange rate data. Surface
      residues that are conserved from archaea to humans and are likely to interact
      with the ribonuclease P RNA or other protein subunits are identified in the
      structure. The model of the aRpp29 protein defined by this work provides an
      essential step toward eventually understanding the overall architecture of
      ribonuclease P.

PMID- 15518564
TI  - A structural and mechanistic study of the oxidation of methionine residues in
      hPTH(1-34) via experiments and simulations.
AB  - The relationship between the conformational properties of 1-34 human parathyroid
      hormone [hPTH(1-34)] and the oxidation of its methionine residues, Met8 and
      Met18, by hydrogen peroxide is analyzed as a function of pH by measuring the
      rates of oxidation and by performing MD simulations with an explicit
      representation of water molecules. Between pH 4 and pH 8, both Met8 and Met18
      have nearly pH independent rates of oxidation, and Met18 is oxidized at a rate
      that is 90-100% of that of freeMet and 10-20% faster than that of Met8. We also
      found that average 2SWCNs calculated from MD simulations correlate well to the
      rates of oxidation of Met8 and Met18. The use of 2SWCNs is based on the mechanism
      that we proposed, the water-mediated mechanism, in which water molecules
      stabilize the transition state via specific interactions, but the transfer of
      protons (acid-catalyzed mechanism) does not play a role [Chu, J. W., and Trout,
      B. L. (2004) J. Am. Chem. Soc. 126 (3), 900-908]. Only at very low pH values, pH
      1 for the oxidation of freeMet, does the acid-catalyzed oxidation mechanism
      become important. For the oxidation of Met8 and Met18 in hPTH(1-34), the acid
      catalyzed mechanism becomes significant at a higher pH value, pH 2, probably due
      to the proximity of nearby acidic residues to Met8 (Glu4) and Met18 (Glu22). In
      this study, we have demonstrated that the chemistry of oxidation and the
      structure of polypeptides can be correlated via a detailed understanding of the
      reaction mechanism, appropriate sampling of configurational space, and a suitable
      choice of a structural property, water coordination number.

PMID- 15518565
TI  - Investigation of the role of the N-terminal proline, the distal heme ligand in
      the CO sensor CooA.
AB  - A unique feature of CooA, a heme-containing transcription factor, is that the N
      terminal proline is the distal heme ligand in the ferrous state, and this ligand
      is displaced upon CO binding. To investigate the importance of Pro(2) in CO
      dependent DNA binding, several CooA variants that alter N-terminal ligation were
      characterized. Electronic absorption, electron paramagnetic resonance, and
      magnetic circular dichroism spectra of these variants provide the most definitive
      evidence that Pro(2) is the distal ligand in Fe(III) CooA. Furthermore, the
      functional and spectroscopic properties of these proteins depended on whether a
      weak ligand occupied the distal heme coordination site: for CooA variants in
      which distal coordination is disrupted, the DNA-binding affinities and Fe(II)-CO
      spectral properties showed an unexpected dependence on the order of CO addition
      and heme reduction. If N-terminal variant samples were incubated with CO before
      the heme was reduced, the proteins displayed DNA-binding affinities and Fe(II)-CO
      spectral characteristics similar to those of wild-type (WT) CooA. However, if the
      same samples were incubated with CO after the heme was reduced, the extent of
      functional and spectral similarity to WT CooA negatively correlated with the
      amount of high-spin heme present in the ferric state. From these data, it was
      inferred that the absence of a distal heme ligand in the ferric state prevents WT
      like CO binding to the ferrous state, and it was hypothesized that correct CO
      binding is inhibited by the collapse of the distal heme pocket upon reduction.
      Together with the observation that L116H CooA, a variant in which His(116)
      replaces Pro(2) as the distal heme ligand, binds CO more slowly than WT CooA,
      these data indicate that the presence of a weak distal heme ligand, not
      specifically ligation by the N-terminal proline, is crucial for proper function.
      The role of Pro(2) in CooA is apparently to direct CO to bind on the distal side
      of heme and to help maintain the integrity of the distal heme pocket during the
      redox-mediated ligand switch.

PMID- 15518566
TI  - In situ effects of mutations of the extrinsic cytochrome c550 of photosystem II
      in Synechocystis sp. PCC6803.
AB  - The H(2)O oxidizing domain of the cyanobacterial photosystem II (PSII) complex
      contains a low potential, c-type cytochrome termed c(550) that is essential for
      the in vivo stability of the PSII complex. A mutant lacking cytochrome c(550)
      (DeltapsbV) in Synechocystis sp. PCC6803 has been further analyzed together with
      a construct in which the distal axial heme iron ligand, histidine 92, has been
      substituted with a methionine (C550-H92M). Heme staining of SDS-PAGE showed that
      the C550-H92M mutation did not disturb the accumulation and heme-binding
      properties of the cytochrome. In DeltapsbV cells, the number of charge separating
      PSII centers was estimated to be 56% of the wild type, but of the existing
      centers, 33% lacked photooxidizable Mn ions. C550-H92M did not discernibly affect
      the intrinsic PSII electron-transfer kinetics compared to the wild type nor did
      it exhibit a significant fraction of centers lacking photooxidizable Mn; however,
      the number of charge separating PSII centers in mutant cells was 69% of the wild
      type. C550-H92M lost photoautotrophic growth ability in the absence of Ca(2+),
      but its growth was not affected by depletion of Cl(-), which differs from
      DeltapsbV. Taken together, the results suggest that in the absence of cytochrome
      c(550) electron transfer on the donor side is retarded perhaps at the level of
      Y(z) to P680(+) transfer, the heme ligand. His92 is not absolutely required for
      assembly of functional PSII centers; however, replacement by methionine prevents
      normal accumulation of PSII centers in the thylakoid membranes and alters the
      Ca(2+) requirement of PSII. The results are discussed in terms of current
      understanding of the Ca(2+) site of PSII.

PMID- 15518567
TI  - Structural stability of the PsbQ protein of higher plant photosystem II.
AB  - We have characterized the stability and folding behavior of the isolated
      extrinsic PsbQ protein of photosystem II (PSII) from a higher plant, Spinacia
      oleracea, using intrinsic protein fluorescence emission and near- and far-UV
      circular dichroism (CD) spectroscopy in combination with differential scanning
      calorimetry (DSC). Experimental results reveal that both chemical denaturation
      using guanidine hydrochloride (GdnHCl) and thermal unfolding of PsbQ proceed as a
      two-state reversible process. The denaturation free-energy changes (DeltaG(D)) at
      20 degrees C extrapolated from GdnHCl (4.0 +/- 0.6 kcal mol(-1)) or thermal
      unfolding (4.4 +/- 0.8 kcal mol(-1)) are very close. Moreover, the far-UV CD
      spectra of the denatured PsbQ registered at 90 degrees C in the absence and
      presence of 6.0 M GdnHCl superimpose, leading us to conclude that both denatured
      states of PsbQ are structurally and energetically similar. The thermal unfolding
      of PsbQ has been also characterized by CD and DSC over a wide pH range. The
      stability of PsbQ is at its maximum at pH comprised between 5 and 8, being wider
      than the optimal pH for oxygen evolution in the lumen of thylakoid membranes. In
      addition, no significant structural changes were detected in PsbQ between 50 and
      55 degrees C in the pH range of 3-8, suggesting that PsbQ behaves as a soluble
      and stable particle in the lumen when it detaches from PSII under physiological
      stress conditions such as high temperature (45-50 degrees C) or low pH (<5.0).
      Sedimentation experiments showed that, in solution at 20 degrees C, the PsbQ
      protein is a monomer with an elongated shape.

PMID- 15518568
TI  - Characterization of two type 1 Cu sites of Hyphomicrobium denitrificans nitrite
      reductase: a new class of copper-containing nitrite reductases.
AB  - We report (1) the amino acid sequence of Hyphomicrobium denitrificans nitrite
      reductase (HdNIR), containing two type 1 Cu sites and one type 2 Cu site; (2) the
      expression and preparation of wild-type HdNIR and two mutants replacing the Cys
      ligand of each type 1 Cu with Ala; and (3) their spectroscopic and functional
      characterization. The open-reading frame of 50-kDa HdNIR is composed of the 15
      kDa N-terminal domain having a type 1 Cu-binding motif like cupredoxins and the
      35-kDa C-terminal domain having type 1 Cu-binding and type 2 Cu-binding motifs
      such as common nitrite reductases (NIRs). Moreover, the amino acid sequences of
      the N- and C-terminal domains are homologous to those of plastocyanins and NIRs,
      respectively. The point mutation of the Cys ligand of each type 1 Cu with Ala
      gives two mutants, C114A and C260A, possessing one type 1 Cu and one type 2 Cu.
      The spectroscopic data of C114A reveal that the C-terminal NIR-like domain has
      the green type 1 Cu (type 1 Cu(C)), showing two intense absorption peaks at 455
      (epsilon = 2600 M(-1) cm(-1)) and 600 nm (epsilon = 2800 M(-1) cm(-1)) and a
      rhombic EPR signal like those of the green type 1 Cu of Achromobacter
      cycloclastes NIR (AcNlR). The spectroscopic data of C260A elucidate that the N
      terminal Pc-like domain in HdNIR contains the blue type 1 Cu (type 1 Cu(N)),
      exhibiting an intense absorption band at 605 nm (epsilon = 2900 M(-1) cm(-1)) and
      an axial EPR signal like those of the blue type 1 Cu of Alcaligenes xylosoxidans
      NIR (AxNIR). The sum of the visible absorption or EPR spectra of C114A and C260A
      is almost equal to the corresponding spectrum of wild-type HdNIR. The
      spectroscopic characterization of the type 1 Cu indicates that the geometries of
      the type 1 Cu(N) and Cu(C) sites are slightly distorted tetrahedral (or axially
      elongated bipyramidal) and flattened tetrahedral, respectively. In the cyclic
      voltammograms, the midpoint potentials (E(1/2)), probably because of the type 1
      Cu ions of C114A and C260A, are observed at +321 and +336 mV versus normal
      hydrogen electrode (NHE) at pH 7.0, respectively. These values, which are close
      to each other, are more positive than those ( approximately +0.24-0.28 V at pH
      7.0) of the type 1 Cu sites of AcNIR and AxNIR. The electron-accepting capability
      of C114A from cytochrome c(550) is almost similar to that of wild-type HdNIR,
      whereas that of C260A is very low. This suggests that the type 1 Cu(C) in the C
      terminal domain is essential for the enzyme functions of HdNIR.

PMID- 15518569
TI  - SOUL in mouse eyes is a new hexameric heme-binding protein with characteristic
      optical absorption, resonance Raman spectral, and heme-binding properties.
AB  - SOUL is specifically expressed in the retina and pineal gland and displays more
      than 40% sequence homology with p22HBP, a heme protein ubiquitously expressed in
      numerous tissues. SOUL was purified as a dimer in the absence of heme from the
      Escherichia coli expression system but displayed a hexameric structure upon heme
      binding. Heme-bound SOUL displayed optical absorption and resonance Raman spectra
      typical of 6-coordinate low-spin heme protein, with one heme per monomeric unit
      for both the Fe(III) and Fe(II) complexes. Spectral data additionally suggest
      that one of the axial ligands of the Fe(III) heme complex is His. Mutation of
      His42 (the only His of SOUL) to Ala resulted in loss of heme binding, confirming
      that this residue is an axial ligand of SOUL. The K(d) value of heme for SOUL was
      estimated as 4.8 x 10(-9) M from the association and dissociation rate constants,
      suggesting high binding affinity. On the other hand, p22HBP was obtained as a
      monomer containing one heme per subunit, with a K(d) value of 2.1 x 10(-11) M.
      Spectra of heme-bound p22HBP were different from those of SOUL but similar to
      those of heme-bound bovine serum albumin in which heme bound to a hydrophobic
      cavity with no specific axial ligand coordination. Therefore, the heme-binding
      properties and coordination structure of SOUL are distinct from those of p22HBP,
      despite high sequence homology. The physiological role of the new heme-binding
      protein, SOUL, is further discussed in this report.

PMID- 15518570
TI  - Light-harvesting complex 1 stabilizes P+QB- charge separation in reaction centers
      of Rhodobacter sphaeroides.
AB  - The kinetics of charge recombination following photoexcitation by a laser pulse
      have been analyzed in the reaction center-light harvesting complex 1 (RC-LH1)
      purified from the photosynthetic bacterium Rhodobacter sphaeroides. In RC-LH1
      core complexes isolated from photosynthetically grown cells P(+)Q(B)(-)
      recombines with an average rate constant, k approximately 0.3 s(-1), more than
      three times smaller than that measured in RC deprived of the LH1 (k approximately
      1 s(-1)). A comparable, slowed recombination kinetics is observed in RC-LH1
      complexes purified from a pufX-deleted strain. Slowing of the charge
      recombination kinetics is even more pronounced in RC-LH1 complexes isolated from
      wild-type semiaerobically grown cells (k approximately 0.2 s(-1)). Since the
      kinetics of P(+)Q(A)(-) recombination is unaffected by the presence of the
      antenna, the P(+)Q(B)(-) state appears to be energetically stabilized in core
      complexes. Determinations of the ubiquinone-10 (UQ(10)) complement associated
      with the purified RC-LH1 complexes always yield UQ(10)/RC ratios larger than 10.
      These quinone molecules are functionally coupled to the RC-LH1 complex, as judged
      from the extent of exogenous cytochrome c(2) rapidly oxidized under continuous
      light excitation. Analysis of P(+)Q(B)(-) recombination, based on a kinetic model
      which considers fast quinone equilibrium at the Q(B) binding site, indicates that
      the slowing down of charge recombination kinetics observed in RC-LH1 complexes
      cannot be explained solely by a quinone concentration effect and suggests that
      stabilization of the light-induced charge separation is predominantly due to
      interaction of the Q(B) site with the LH1 complex. The high UQ(10) complements
      detected in RC-LH1 core complexes, but not in purified light-harvesting complex 2
      and in RC, are proposed to reflect an in vivo heterogeneity in the distribution
      of the quinone pool within the chromatophore bilayer.

PMID- 15518571
TI  - Human ribosomal protein S3 interacts with DNA base excision repair proteins
      hAPE/Ref-1 and hOGG1.
AB  - The human ribosomal protein S3 (hS3) possesses associated activities that suggest
      alternative roles beyond its participation in protein translation. For example,
      it is capable of cleaving apurinic/apyrimidinic (AP) DNA via a beta-elimination
      reaction, an activity that is missing in partially purified extracts of xeroderma
      pigmentosum group-D fibroblasts. In a recent study, we showed by surface plasmon
      resonance (SPR) that hS3 also has a very high apparent binding affinity for 7,8
      dihydro-8-oxoguanine (8-oxoG) and AP sites in DNA. Using the same SPR technology,
      it is shown here that hS3 positively interacts with the human base excision
      repair (BER) enzymes N-glycosylase/AP lyase OGG1 and APE/Ref-1. Using a DNA
      substrate that allows for the detection of 8-oxoG repair, we also show that hOGG1
      N-glycosylase activity becomes increasingly more robust in the presence of hS3.
      Human S3 was found to co-immunoprecipitate with both hOGG1 and APE/Ref-1,
      indicating that these proteins physically interact with one another. These
      results raise the possibility that hS3 not only functions as a ribosomal protein
      but, in addition, may influence repair activities at sites of DNA damage.

PMID- 15518572
TI  - Influence of sequence context and length on the structure and stability of
      triplet repeat DNA oligomers.
AB  - Genetic expansion diseases have been linked to the properties of triplet repeat
      DNA sequences during replication. The most common triplet repeats associated with
      such diseases are CAG, CCG, CGG, and CTG. It has been suggested that gene
      expansion occurs as a result of hairpin formation of long stretches of these
      sequences on the leading daughter strand synthesized during DNA replication
      [Gellibolian, R., Bacolla, A., and Wells, R. D. (1997) J. Biol. Chem. 272, 16793
      7]. To test the biophysical basis for this model, oligonucleotides of general
      sequence (CNG)(n), where N = A, C, G, or T and n = 4, 5, 10, 15, or 25, were
      synthesized and characterized by circular dichroism (CD) spectropolarimetry,
      optical melting studies, and differential scanning calorimetry (DSC). The goal of
      these studies was to evaluate the influence of sequence context and oligomer
      length on their secondary structures and stabilities. The results indicate that
      all single oligomers, even those as short as 12 nucleotides, form stable hairpin
      structures at 25 degrees C. Such hairpins are characterized by the presence of
      N:N mismatched base pairs sandwiched between G:C base pairs in the stems and
      loops of three to four unpaired bases. Thermodynamic analysis of these structures
      reveals that their stabilities are influenced by both the sequence of the
      particular oligomer and its length. Specifically, the stability order of CGG >
      CTG > CAG > CCG was observed. In addition, longer oligomers were found to be more
      stable than shorter oligomers of the same sequence. However, a stability plateau
      above 45 nucleotides suggests that the length dependence reaches a maximum value
      where the stability of the G:C base pairs can no longer compensate the
      instability of the N:N mismatches in the stems of the hairpins. The results are
      discussed in terms of the above model proposed for gene expansion.

PMID- 15518573
TI  - SV40 DNA replication inhibition by the monofunctional DNA alkylator Et743.
AB  - Ecteinascidin 743 (Et743) is a highly cytotoxic anticancer agent isolated from
      the squirt Ecteinascidia turbinate, which alkylates DNA in the minor groove at GC
      rich sequences resulting in an unusual bending toward the major groove. The
      ability of Et743 to block DNA replication was studied using the well-established
      simian virus (SV40) model for mammalian DNA replication in cells and cell-free
      extracts. Intracellular SV40 DNA isolated from Et743-treated BSC-1 cells was
      analyzed by native, two-dimensional agarose gel electrophoresis. A low frequency
      of Et743 adducts detected at 30-100 nM drug concentrations inhibited SV40 origin
      activity and induced formation of unusual DNA replication intermediates. Under
      cell-free conditions, only a high Et743 adduct frequency reduced SV40 DNA
      synthesis. Comparative studies involving related DNA alkylators, tomamycin and
      saframycin A, revealed inhibition of SV40 DNA replication in cells at
      concentrations approximately 10 times higher than Et743. Under cell-free
      conditions tomamycin- or saframycin-A-adducted DNA templates inhibited DNA
      synthesis similarly to Et743. Et743 appears to be unusual among other alkylators,
      because its adducts strongly inhibit intracellular SV40 DNA replication but are
      relatively weak as cis inhibitors as measured under cell-free conditions.

PMID- 15518574
TI  - Acid denaturation and refolding of green fluorescent protein.
AB  - Green fluorescent protein from the jellyfish Aequorea victoria can serve as a
      good model protein to understand protein folding in a complex environment with
      molecular chaperones and other macromolecules such as those in biological cells,
      but little is known about the detailed mechanisms of the in vitro folding of
      green fluorescent protein itself. We therefore investigated the kinetic refolding
      of a mutant (F99S/M153T/V163A) of green fluorescent protein, which is known to
      mature more efficiently than the wild-type protein, from the acid-denatured
      state; refolding was observed by chromophore fluorescence, tryptophan
      fluorescence, and far-UV CD, using a stopped-flow technique. In this study, we
      demonstrated that the kinetics of the refolding of the mutant have at least five
      kinetic phases and involve nonspecific collapse within the dead time of a stopped
      flow apparatus and the subsequent formation of an on-pathway intermediate with
      the characteristics of the molten globule state. We also demonstrated that the
      slowest phase and a major portion of the second slowest phase were rate-limited
      by slow prolyl isomerization in the intermediate state, and this rate limitation
      accounts for a major portion of the observed kinetics in the folding of green
      fluorescent protein.

PMID- 15518575
TI  - A piezoelectric quartz crystal biosensor: the use of two single cysteine mutants
      of the periplasmic Escherichia coli glucose/galactose receptor as target proteins
      for the detection of glucose.
AB  - We have examined the potential utility of a glucose biosensor that employs the
      glucose/galactose receptor of Escherichia coli with a quartz crystal microbalance
      (QCM). Two different genetically engineered mutant proteins were utilized, each
      involving the incorporation of a single cysteine into the amino acid sequence of
      the protein. The proteins were immobilized on the surface of a piezoelectric
      crystal by a direct sulfur-gold linkage. Since the cysteines were located at
      different positions in the sequence, the receptors attach to the surface with
      different orientations. Considering only mass effects, the target sugars for this
      receptor are predicted to be too small to be detectable with a QCM. However, our
      sensors indicated measurable and reproducible frequency responses when
      immobilized receptor was exposed to sugar. This unexpectedly large frequency
      response occurs because the protein film is transformed from a viscous layer to a
      more rigid nondissipative film. The QCM can detect these changes because of the
      direct linkage of the proteins to the surface. Calculations of the frequency
      response expected for a viscoelastic film with different rheological
      characteristics support this hypothesis. This study is significant because it
      illustrates a widened applicability for the QCM methodology to protein systems
      that bind small molecules and undergo ligand-induced conformational changes.

PMID- 15518576
TI  - Detection of TAP family dimerizations by an in vivo assay in mammalian cells.
AB  - The transporter associated with antigen presentation (TAP) is an ATP-binding
      cassette (ABC) protein which transports peptides for presentation to the immune
      system. TAP is composed of two half transporters, TAP1 (ABCB2) and TAP2 (ABCB3),
      which heterodimerize to function. In humans, the TAP family consists of TAP1,
      TAP2, and TAPL (ABCB9). While the TAP1-TAP2 complex is well characterized, TAPL's
      dimerization state and function are unknown. To identify interactions within the
      human TAP family, we adapted the dihydrofolate reductase protein-fragment
      complementation assay (DHFR PCA) to half ABC transporters. This assay has been
      shown to be suitable for the study of membrane-bound proteins in vivo [Remy, I.,
      Wilson, I. A., and Michnick, S. W. (1999) Science 283, 990-993]. With this
      method, in vivo TAP1-TAP2 heterodimerization was confirmed, no homodimerizations
      were detected with TAP1 or TAP2, and TAPL did not show any interaction with TAP1
      or TAP2. However, we found strong evidence that TAPL forms homodimers. These
      results provide evidence of a novel homomeric TAPL interaction and demonstrate
      that the DHFR PCA will be of general utility in studies of half ABC transporter
      interactions in vivo.

PMID- 15518577
TI  - Identification of an unusual [2Fe-2S]-binding motif in the CDP-6-deoxy-D-glycero
      l-threo-4-hexulose-3-dehydrase from Yersinia pseudotuberculosis: implication for
      C-3 deoxygenation in the biosynthesis of 3,6-dideoxyhexoses.
AB  - CDP-6-deoxy-L-threo-D-glycero-4-hexulose-3-dehydrase (E(1)) catalyzes the C-3
      deoxygenation in the biosynthesis of 3,6-dideoxyhexoses in Yersinia
      pseudotuberculosis. E(1) is a pyridoxamine 5'-phosphate (PMP)-dependent enzyme
      that also contains a [2Fe-2S] center. This iron-sulfur cluster is catalytically
      essential, since removal of the [2Fe-2S] center leads to inactive enzyme. To
      identify the [2Fe-2S] core in E(1) and to study the effect of impairing the iron
      sulfur cluster on the activity of E(1), a series of E(1) cysteine mutants were
      constructed and their catalytic properties were characterized. Our results show
      that E(1) displays a cluster-binding motif (C-X(57)-C-X(1)-C-X(7)-C) that has not
      been observed previously for [2Fe-2S] proteins. The presence of such an unusual
      iron-sulfur cluster in E(1), along with the replacement of the active site lysine
      by a histidine residue (H220), reflects a distinct evolutionary path for this
      enzyme. The cysteine residues (C193, C251, C253, C261) implicated in the binding
      of the iron-sulfur cluster in E(1) are conserved in the sequences of its
      homologues. It is likely that E(1) and its homologues constitute a new subclass
      in the family of iron-sulfur proteins, which are distinguished not only by their
      cluster ligation patterns but also by the chemistry used in catalyzing a simple,
      albeit mechanistically challenging, reaction.

PMID- 15518578
TI  - The structure of rabbit extracellular superoxide dismutase differs from the human
      protein.
AB  - The cDNA sequence encoding rabbit, mouse, and rat extracellular superoxide
      dismutase (EC-SOD) predicts that the protein contains five cysteine residues.
      Human EC-SOD contains an additional cysteine residue and folds into two forms
      with distinct disulfide bridge patterns. One form is enzymatically active (aEC
      SOD), while the other is inactive (iEC-SOD). Due to the lack of the additional
      cysteine residue rabbit, mouse, and rat EC-SOD are unable to generate an inactive
      fold identical to human iEC-SOD. The amino acid sequences predict the formation
      of aEC-SOD only, but other folding variants cannot be ruled out based on the
      heterogeneity observed for human EC-SOD. To test this, we purified EC-SOD from
      rabbit plasma and determined the disulfide bridge pattern. The results revealed
      that the disulfide bridges are homogeneous and identical to human aEC-SOD. Four
      cysteine residues are involved in two intra-disulfide bonds while the C-terminal
      cysteine residue forms an intersubunit disulfide bond. No evidence for other
      folding variants was detected. These findings show that rabbit EC-SOD exists as
      an enzymatically active form only. The absence of iEC-SOD in rabbits suggests
      that the structure and aspects of the physiological function of EC-SOD differs
      significantly between rabbit and humans. This is an important notion to take when
      using these animals as model systems for oxidative stress.

PMID- 15518580
TI  - Identification and mechanism of a bacterial hydrolyzing UDP-N-acetylglucosamine 2
      epimerase.
AB  - This paper reports the first identification of a fully functional hydrolyzing UDP
      N-acetylglucosamine 2-epimerase from a bacterial source. The epimerase (known as
      SiaA or NeuC) from Neisseria meningitidis MC58 group B is shown to catalyze the
      conversion of UDP-GlcNAc into ManNAc and UDP in the first step of sialic acid (N
      acetylneuraminic acid) biosynthesis. The mechanism is proposed to involve an anti
      elimination of UDP to form 2-acetamidoglucal as an intermediate, followed by the
      syn addition of water. The observation that the alpha-anomer of ManNAc is the
      true product and that solvent deuterium is incorporated at C-2 is consistent with
      this mechanism. The use of the (18)O-labeled substrate confirms that the overall
      hydrolysis reaction proceeds via cleavage of the C-O bond. Furthermore, the
      putative intermediate 2-acetamidoglucal is shown to serve as a catalytically
      competent substrate and is enzymatically hydrated to give ManNAc exclusively.
      Isotope effect studies show that cleavage of the C-H bond is not rate limiting
      during catalysis. Mutagenesis studies show that three active site carboxylate
      residues are crucial for catalysis. In two of the mutants that were studied
      (E122Q and D131N), 2-acetamidoglucal was released from the active site during
      catalysis, providing direct evidence that the enzyme is capable of catalyzing the
      anti elimination of UDP from UDP-GlcNAc.

PMID- 15518579
TI  - Chromium(VI) enhances (+/-)-anti-7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy
      7,8,9,10-tetrahydrobenzo[a]pyrene-induced cytotoxicity and mutagenicity in
      mammalian cells through its inhibitory effect on nucleotide excision repair.
AB  - Chromium(VI) [Cr(VI)], a ubiquitous environmental contaminant, is a well-known
      carcinogen to both humans and experimental animals, although it is a weak mutagen
      by itself. Occupational exposure to Cr(VI) is strongly associated with a high
      incidence of lung cancer, but the underlying mechanisms remain unclear. Tobacco
      smoking is the major cause of lung cancer, and polycyclic aromatic hydrocarbons
      (PAHs) in tobacco smoke are the major etiological agents. Since humans are
      frequently exposed to both Cr(VI) and PAHs, it is possible that Cr(VI) and PAHs
      have a synergistic effect on mutagenecity and cytotoxicity that contributes to
      the high incidence of lung cancer associated with exposure to both agents. In
      this study, we tested this possibility by determining the effect of Cr(VI)
      exposure on (+/-)-anti-7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10
      tetrahydrobenzo[a]pyrene (BPDE, an active metabolite of PAHs) induced
      cytotoxicity, mutagenicity, and DNA adduct formation in Chinese hamster ovary
      (CHO) cells. Using the adenine phosphoribosyltransferase (APRT(+)) --> APRT(-)
      forward mutation assay, we found that while Cr(VI) alone induced low mutation
      frequency, it greatly enhanced BPDE-induced mutations in nucleotide excision
      repair (NER)-proficient CHO cells. Cr(VI) exposure also greatly enhanced BPDE
      induced killing in NER-proficient cells. It is known that the cytotoxicity and
      mutagenicity of BPDE are mainly caused by the formation of DNA adduct, which are
      removed by NER. To test the possibility that the enhancement of cytotoxicity and
      mutagenicity by Cr(VI) is caused by the inhibition of NER, NER-deficient cells
      were used, and the enhancement effects of Cr(VI) were not observed in those
      cells. We further found that while Cr(VI) exposure does not change the total BPDE
      DNA adduct formation, it significantly inhibited the repair of BPDE-DNA adducts
      from genomic DNA in NER-proficient cells. Using a host cell reactivation assay,
      we found that the repair of BPDE-DNA adduct in a luciferase reporter gene is
      greatly inhibited after Cr(VI) exposure in NER-proficient cells while not in NER
      deficient cells. Together these results clearly demonstrate that Cr(VI) exposure
      can greatly enhance the mutagenicity and cytotoxicity of PAHs by inhibiting the
      cellular NER pathway, and this may constitute an important mechanism for Cr(VI)
      induced human carcinogenesis.

PMID- 15518581
TI  - The HevCaLP protein mediates binding specificity of the Cry1A class of Bacillus
      thuringiensis toxins in Heliothis virescens.
AB  - Retrotransposon-mediated disruption of the BtR-4 gene encoding the Heliothis
      virescens cadherin-like protein (HevCaLP) is linked to high levels of resistance
      in the YHD2 strain to Cry1Ac toxin from Bacillus thuringiensis. This suggests
      that HevCaLP functions as a Cry1Ac toxin receptor on the surface of midgut cells
      in susceptible larvae and that the BtR-4 gene disruption eliminates this protein
      in resistant larvae. However, Cry1Ac toxin binding to HevCaLP is yet to be
      reported. We used the polymerase chain reaction and immunoblotting as tools to
      discriminate between individual H. virescens larval midguts from susceptible
      (YDK) and resistant (CXC, KCBhyb, and YHD2-B) strains according to their BtR-4
      gene disruption genotype and phenotype. This approach allowed us to test the
      correlation between BtR-4 gene disruption, lack of HevCaLP, and altered Cry1A
      toxin binding. Toxin-binding assays using brush border membrane vesicles revealed
      that a wild-type BtR-4 allele is necessary for HevCaLP production and Cry1Aa
      toxin binding, while most of Cry1Ab and Cry1Ac binding was independent of the BtR
      4 genotype. Moreover, toxin competition experiments show that KCBhyb midguts
      lacking HevCaLP are more similar to midguts of the original YHD2 strain than to
      the current YHD2-B strain. This resolves discrepancies in published studies of
      Cry1A binding in YHD2 and supports our earlier suggestion that a separate genetic
      change occurred in YHD2 after appearance of the cadherin disruption, conferring
      even higher resistance in the resulting YHD2-B strain as well as a large
      reduction in Cry1Ab and Cry1Ac binding.

PMID- 15518582
TI  - Prostaphopain B structure: a comparison of proregion-mediated and staphostatin
      mediated protease inhibition.
AB  - Prostaphopain B is the precursor of staphopain B, a papain-type secreted cysteine
      protease from the pathogen Staphylococcus aureus. Here, we describe the 2.5 A
      crystal structure of the proenzyme. Its 21 kDa proregion is organized around a
      central half-barrel or barrel-sandwich hybrid and occludes primed, but not
      nonprimed, sites in the active site cleft of the protease. The structure of the
      mature part of the protease is similar to previously reported staphopain
      structures, and no distortion of the catalytic residues is apparent at 2.5 A
      resolution. A comparison of prostaphopain B with the staphopain B-staphostatin B
      complex shows that the proregion and the inhibitor interact with largely
      nonoverlapping parts of the protease surface. In a modeled complex of
      prostaphopain B with staphostatin B, clashes occur both inside and outside the
      active site cleft, but involve mostly poorly ordered regions of the protein that
      may be mobile.

PMID- 15518587
TI  - Open form of syntaxin-1A is a more potent inhibitor than wild-type syntaxin-1A of
      Kv2.1 channels.
AB  - We have shown that SNARE (soluble N-ethylmaleimide-sensitive fusion protein
      attachment protein receptor) proteins not only participate directly in
      exocytosis, but also regulate the dominant membrane-repolarizing Kv channels
      (voltage-gated K+ channels), such as Kv2.1, in pancreatic beta-cells. In a recent
      report, we demonstrated that WT (wild-type) Syn-1A (syntaxin-1A) inhibits Kv2.1
      channel trafficking and gating through binding to the cytoplasmic C-terminus of
      Kv2.1. During beta-cell exocytosis, Syn-1A converts from a closed form into an
      open form which reveals its active H3 domain to bind its SNARE partners SNAP-25
      (synaptosome-associated protein of 25 kDa) and synaptobrevin. In the present
      study, we compared the effects of the WT Syn-1A and a mutant open form Syn-1A
      (L165A, E166A) on Kv2.1 channel trafficking and gating. When co-expressed in HEK
      293 cells (human embryonic kidney-293 cells), the open form Syn-1A decreased
      Kv2.1 current density more than (P<0.05) the WT Syn-1A (166+/-35 and 371+/-93
      pA/pF respectively; control=911+/-91 pA/pF). Confocal microscopy and
      biotinylation experiments showed that both the WT and open form Syn-1A inhibited
      Kv2.1 expression at the plasma membrane to a similar extent, suggesting that the
      stronger reduction of Kv2.1 current density by the open form compared with the WT
      Syn-1A is probably due to a stronger direct inhibition of channel activity.
      Consistently, dialysis of the recombinant open form Syn-1A protein into Kv2.1
      expressing HEK-293 cells caused stronger inhibition of Kv2.1 current amplitude
      (P<0.05) than the WT Syn-1A protein (73+/-2 and 82+/-3% of the control
      respectively). We found that the H3 but not H(ABC) domain is the putative active
      domain of Syn-1A, which bound to and inhibited the Kv2.1 channel. When co
      expressed in HEK-293 cells, the open-form Syn-1A slowed down Kv2.1 channel
      activation (tau=12.3+/-0.8 ms) much more than (P<0.05) WT Syn-1A (tau=7.9+/-0.8
      ms; control tau=5.5+/-0.6 ms). In addition, only the open form Syn-1A, but not
      the WT Syn-1A, caused a significant (P<0.05) left-shift in the steady-state
      inactivation curve (V(1/2)=33.1+/-1.3 and -29.4+/-1.1 mV respectively; control
      V(1/2)=-24.8+/-2 mV). The present study therefore indicates that the open form of
      Syn-1A is more potent than the WT Syn-1A in inhibiting the Kv2.1 channel. Such
      stronger inhibition by the open form of Syn-1A may limit K+ efflux and thus
      decelerate membrane repolarization during exocytosis, leading to optimization of
      insulin release.

PMID- 15518588
TI  - High sensitivity 1H-NMR spectroscopy of homeopathic remedies made in water.
AB  - BACKGROUND: The efficacy of homeopathy is controversial. Homeopathic remedies are
      made via iterated shaking and dilution, in ethanol or in water, from a starting
      substance. Remedies of potency 12 C or higher are ultra-dilute (UD), i.e. contain
      zero molecules of the starting material. Various hypotheses have been advanced to
      explain how a UD remedy might be different from unprepared solvent. One such
      hypothesis posits that a remedy contains stable clusters, i.e. localized regions
      where one or more hydrogen bonds remain fixed on a long time scale. High
      sensitivity proton nuclear magnetic resonance spectroscopy has not previously
      been used to look for evidence of differences between UD remedies and controls.
      METHODS: Homeopathic remedies made in water were studied via high sensitivity
      proton nuclear magnetic resonance spectroscopy. A total of 57 remedy samples
      representing six starting materials and spanning a variety of potencies from 6 C
      to 10 M were tested along with 46 controls. RESULTS: By presaturating on the
      water peak, signals could be reliably detected that represented H-containing
      species at concentrations as low as 5 microM. There were 35 positions where a
      discrete signal was seen in one or more of the 103 spectra, which should
      theoretically have been absent from the spectrum of pure water. Of these 35,
      fifteen were identified as machine-generated artifacts, eight were identified as
      trace levels of organic contaminants, and twelve were unexplained. Of the
      unexplained signals, six were seen in just one spectrum each. None of the
      artifacts or unexplained signals occurred more frequently in remedies than in
      controls, using a p < .05 cutoff. Some commercially prepared samples were found
      to contain traces of one or more of these small organic molecules: ethanol,
      acetate, formate, methanol, and acetone. CONCLUSION: No discrete signals
      suggesting a difference between remedies and controls were seen, via high
      sensitivity 1H-NMR spectroscopy. The results failed to support a hypothesis that
      remedies made in water contain long-lived non-dynamic alterations of the H
      bonding pattern of the solvent.

PMID- 15518589
TI  - The Molecular Pages of the mesotelencephalic dopamine consortium (DopaNet).
AB  - BACKGROUND: DopaNet http://www.dopanet.org is a Systems Biology initiative that
      aims to investigate precisely and quantitatively all the aspects of
      neurotransmission in a specific neuronal system, the mesotelencephalic dopamine
      system. The project should lead to large-scale models of molecular and cellular
      processes involved in neuronal signaling. A prerequisite is the proper storage of
      knowledge coming from the literature. METHODS: DopaNet Molecular Pages are highly
      structured descriptions of quantitative parameters related to a specific
      molecular complex involved in neuronal signal processing. A Molecular Page is
      built by maintainers who are experts in the field, and responsible for the
      quality of the page content. Each piece of data is identified by a specific
      ontology code, annotated (method of acquisition, species, etc.) and linked to the
      relevant bibliography. The Molecular Pages are stored as XML files, and processed
      through the DopaNet Web Service, which provides functionalities to edit the
      Molecular Pages, to cross-link the Pages and generate the public display, and to
      search them. CONCLUSIONS: DopaNet Molecular Pages are one of the core resources
      of the DopaNet project but should be of widespread utility in the field of
      Systems Neurobiology.

PMID- 15518590
TI  - A common genetic factor underlies hypertension and other cardiovascular
      disorders.
AB  - BACKGROUND: Certain conditions characterised by blood vessel occlusion or
      vascular spasm have been found to cluster together in epidemiological studies.
      However the biological causes for these associations remain controversial. This
      study used a classical twin design to examine whether these conditions are linked
      through shared environmental exposures or by a common underlying genetic
      propensity to vasospasm. METHODS: We investigated the association between
      hypertension, migraine, Raynaud's phenomenon and coronary artery disease in twins
      from a national register. Phenotype status was determined using a questionnaire
      and the genetic and environmental association between phenotypes was estimated
      through variance components analysis. RESULTS: Responses were obtained from 2,204
      individuals comprising 525 monozygotic and 577 dizygotic pairs. There was a
      significant genetic contribution to all four traits with heritabilities ranging
      from 0.34 to 0.64. Multivariate model-fitting demonstrated that a single common
      genetic factor underlies the four conditions. CONCLUSIONS: We have confirmed an
      association between hypertension, migraine, Raynaud's phenomenon and coronary
      artery disease, and shown that a single genetic factor underlies them. The
      demonstration of a shared genetic factor explains the association between them
      and adds weight to the theory of an inherited predisposition to vasospasm.

PMID- 15518591
TI  - A two-layered mechanical model of the rat esophagus. Experiment and theory.
AB  - BACKGROUND: The function of esophagus is to move food by peristaltic motion which
      is the result of the interaction of the tissue forces in the esophageal wall and
      the hydrodynamic forces in the food bolus. The structure of the esophagus is
      layered. In this paper, the esophagus is treated as a two-layered structure
      consisting of an inner collagen-rich submucosa layer and an outer muscle layer.
      We developed a model and experimental setup for determination of elastic moduli
      in the two layers in circumferential direction and related the measured elastic
      modulus of the intact esophagus to the elastic modulus computed from the elastic
      moduli of the two layers. METHODS: Inflation experiments were done at in vivo
      length and pressure-diameters relations were recorded for the rat esophagus.
      Furthermore, the zero-stress state was taken into consideration. RESULTS: The
      radius and the strain increased as function of pressure in the intact as well as
      in the individual layers of the esophagus. At pressures higher than 1.5 cmH2O the
      muscle layer had a larger radius and strain than the mucosa-submucosa layer. The
      strain for the intact esophagus and for the muscle layer was negative at low
      pressures indicating the presence of residual strains in the tissue. The stress
      strain curve for the submucosa-mucosa layer was shifted to the left of the curves
      for the muscle layer and for the intact esophagus at strains higher than 0.3. The
      tangent modulus was highest in the submucosa-mucosa layer, indicating that the
      submucosa-mucosa has the highest stiffness. A good agreement was found between
      the measured elastic modulus of the intact esophagus and the elastic modulus
      computed from the elastic moduli of the two separated layers.

PMID- 15518592
TI  - Recruiting pregnant smokers for a placebo-randomised controlled trial of nicotine
      replacement therapy.
AB  - BACKGROUND: Smoking in pregnancy is a public health problem and effective methods
      for reducing this are required. Although nicotine replacement therapy (NRT) is
      effective for smoking cessation in non-pregnant people, there is no direct
      evidence concerning its effectiveness in pregnancy. Despite this, clinical
      guidelines recommend the cautious use of NRT during pregnancy. Randomised
      controlled trials are needed to determine the safety and efficacy of NRT when
      used by pregnant women for smoking cessation, but the feasibility of recruiting
      women to such trials is unknown. Consequently, in this study we aimed to
      determine i) the feasibility of recruiting women to a RCT of NRT in pregnancy as
      they attend hospital antenatal ultrasound examinations, ii) the proportion of
      such women who are eligible for and interested in trial enrollment and iii)
      research staff perceptions of how one method of trial recruitment could be
      improved. METHODS: During a one month period, all women attending for antenatal
      ultrasound examination in an English teaching hospital were asked to complete a
      questionnaire which determined their eligibility to enroll in a proposed placebo
      controlled randomised trial investigating the effectiveness of NRT in pregnancy.
      Women who were eligible to participate were asked whether they would do so and
      those who accepted enrollment were offered an appointment with a smoking
      cessation advisor. RESULTS: Over 99% (851/858) of women agreed to complete a
      questionnaire about smoking habits whilst waiting for ultrasound examinations.
      10.3% (88/851) of women attending for antenatal ultrasound fitted eligibility
      criteria for a proposed RCT of NRT in pregnancy, but only 3.6% [(31/851), 95% CI,
      2.4 to 4.9%] indicated on the questionnaire that they would like to take part in
      a study involving randomisation to placebo or active patches. Researchers offered
      trial enrollment to 26 of these 31 women and 96% (25) accepted. Staff recruiting
      women believed that trial recruitment would be maximised if women attending the
      ultrasound department knew about trial recruitment before attending and greater
      staff resources were made available for this. It was also perceived that women
      generally under-reported the amount they smoked on questionnaires completed
      whilst waiting in ultrasound department areas. CONCLUSIONS: It is feasible to
      recruit women for a trial of NRT in pregnancy as they wait for antenatal
      ultrasound examinations. Using similar recruitment methods, researchers can
      expect to recruit between 24 and 49 women per 1000 approached.

PMID- 15518593
TI  - A systematic review of the effectiveness of antimicrobial rinse-free hand
      sanitizers for prevention of illness-related absenteeism in elementary school
      children.
AB  - BACKGROUND: Absenteeism due to communicable illness is a major problem
      encountered by North American elementary school children. Although handwashing is
      a proven infection control measure, barriers exist in the school environment,
      which hinder compliance to this routine. Currently, alternative hand hygiene
      techniques are being considered, and one such technique is the use of
      antimicrobial rinse-free hand sanitizers. METHODS: A systematic review was
      conducted to examine the effectiveness of antimicrobial rinse-free hand sanitizer
      interventions in the elementary school setting. MEDLINE, EMBASE, Biological
      Abstract, CINAHL, HealthSTAR and Cochrane Controlled Trials Register were
      searched for both randomized and non-randomized controlled trials. Absenteeism
      due to communicable illness was the primary outcome variable. RESULTS: Six
      eligible studies, two of which were randomized, were identified (5 published
      studies, 1 published abstract). The quality of reporting was low. Due to a large
      amount of heterogeneity and low quality of reporting, no pooled estimates were
      calculated. There was a significant difference reported in favor of the
      intervention in all 5 published studies. CONCLUSIONS: The available evidence for
      the effectiveness of antimicrobial rinse-free hand sanitizer in the school
      environment is of low quality. The results suggest that the strength of the
      benefit should be interpreted with caution. Given the potential to reduce student
      absenteeism, teacher absenteeism, school operating costs, healthcare costs and
      parental absenteeism, a well-designed and analyzed trial is needed to optimize
      this hand hygiene technique.

PMID- 15518594
TI  - The impact of antidepressant treatment on population health: synthesis of data
      from two national data sources in Canada.
AB  - BACKGROUND: In randomized, controlled trials, antidepressant medications have
      been shown to reduce the duration of major depressive episodes and to reduce the
      frequency of relapse during long-term treatment. The epidemiological impact of
      antidepressant use on episode duration and relapse frequency, however, has not
      been described. METHODS: Data from two Canadian general health surveys were used
      in this analysis: the National Population Health Survey (NPHS) and the Canadian
      Community Health Survey (CCHS). The NPHS is a longitudinal study that collected
      data between 1994 and 2000. These longitudinal data allowed an approximation of
      episode incidence to be calculated. The cross-sectional CCHS allowed estimation
      of episode duration. The surveys used the same sampling frame and both
      incorporated a Short Form version of the Composite International Diagnostic
      Interview. RESULTS: Episodes occurring in antidepressant users lasted longer than
      those in non-users. The apparent incidence of major depressive episodes among
      those taking antidepressants was higher than that among respondents not taking
      antidepressants. Changes in duration and incidence over the data collection
      interval were not observed. CONCLUSIONS: The most probable explanation for these
      results is confounding by indication and/or severity: members of the general
      population who are taking antidepressants probably have more highly recurrent and
      more severe mood disorders. In part, this may have been due to the use of a brief
      predictive diagnostic interview, which may be prone to detection of sub-clinical
      cases. Whereas antidepressant use increased considerably over the data-collection
      period, differences in episode incidence and duration over time were not
      observed. This suggests that the impact of antidepressant medications on
      population health may have been less than expected.

PMID- 15518595
TI  - Alteration of T cell immunity by lentiviral transduction of human monocyte
      derived dendritic cells.
AB  - BACKGROUND: Dendritic cells (DCs) are professional antigen-presenting cells that
      play important roles during human immunodeficiency virus type 1 (HIV-1)
      infection. HIV-1 derived lentiviral vectors (LVs) transduce DCs at high
      efficiency but their effects on DC functions have not been carefully studied.
      Modification of DCs using LVs may lead to important applications in
      transplantation, treatment of cancer, autoimmune and infectious diseases.
      RESULTS: Using DCs prepared from multiple blood donors, we report that LV
      transduction of DCs resulted in altered DC phenotypes and functions. Lentiviral
      transduction of DCs resulted in down-regulation of cell surface molecules
      including CD1a, co-stimulatory molecules CD80, CD86, ICAM-1, and DC-SIGN. DCs
      transduced with LVs displayed a diminished capacity to polarize naive T cells to
      differentiate into Th1 effectors. This impaired Th1 response could be fully
      corrected by co-transduction of DCs with LVs encoding interleukin-12 (IL-12),
      interferon-gamma (IFN-gamma), or small interfering RNA (siRNA) targeting IL-10.
      CONCLUSIONS: DCs transduced with LVs in vitro displayed diminished Th1 functions
      due to altered DC phenotypes. Our study addresses an important issue concerning
      lentiviral infection and modification of DC functions, and provides a rational
      approach using LVs for immunotherapy.

PMID- 15518596
TI  - Long-term effects of radiation therapy on cognitive and endocrine function in
      children with leukemia and brain tumors.
AB  - BACKGROUND: As the number of long-term survivors of childhood cancer has grown,
      it has become increasingly clear that central nervous system therapy may have
      serious long-term effects on cognition and endocrine function. These
      complications have been studied most extensively in children with brain tumors
      and leukemia. REVIEW SUMMARY: Children with acute lymphoblastic leukemia
      previously treated with cranial irradiation are at risk for cognitive decline.
      Chemotherapy-only regimens, which rely on high-dose frequently administered
      methotrexate, are also associated with producing cognitive dysfunction. Children
      irradiated for brain tumors are even more vulnerable. Risk factors include
      perioperative morbidity, young age, large-volume high-dose cranial irradiation,
      supra-tentorial location of tumor, moyamoya syndrome, and leukoencephalopathy.
      Cognitive decline is progressive over at least a decade. The most common
      radiation-induced endocrinopathies are hypothyroidism and growth hormone
      deficiency. Treatment effects on growth are multifactorial and include growth
      hormone deficiency,spinal shortening, precocious puberty, undetected
      hypothyroidism,and poor nutrition. Fifty percent to 80% of children treated with
      craniospinal radiation for brain tumors will experience growth failure. In hopes
      of reducing neurotoxicity, current treatments limit the dose and volume of
      radiation while adding chemotherapy. Results have not been uniformly positive,
      however, and may increase toxicity in some cases. CONCLUSIONS: The standard of
      care in 2004 is that children who have been treated for brain tumors and leukemia
      should be monitored for cognitive and endocrine dysfunction. Until effective non
      neurotoxic treatment is identified, long-term effects assessments are essential
      to maximize the quality of life of survivors of childhood cancer.

PMID- 15518597
TI  - The diabetic neuropathies.
AB  - BACKGROUND: Diabetes remains the most common cause of neuropathy in the United
      States and is a significant source of morbidity and mortality, accounting for
      substantial suffering and billions of dollars in health care expenditures each
      year. REVIEW SUMMARY: Our insight into the pathophysiology of the diabetic
      neuropathies has increased considerably over the last decade. aided by advances
      in the basic science of diabetes itself. A wide variety of potential mechanisms
      for nerve injury in diabetes has been identified, including the polyol pathway of
      glucose metabolism, oxidative nerve injury, the deposition of advanced
      glycosylation end products within the nerve and the effects of vascular
      insufficiency, among others. Diabetic neuropathy may take a variety of clinical
      forms beyond the well-known distal symmetric neuropathy, many of which are often
      misdiagnosed or overlooked entirely, sometimes with serious consequences for the
      patient. Proper therapy after diagnosis is also critical and may include not only
      primary management, but also treatment of painful diabetic neuropathy through an
      expanding repertoire of increasingly effective pharmacologic agents. Though
      primary treatment trials have not yet provided effective therapies, ongoing and
      future trials offer continuing promise. CONCLUSIONS: The diabetic neuropathies
      are exceedingly common, but often improperly diagnosed and incompletely treated.
      A proper understanding of the mechanisms underlying these diseases and the
      clinical recognition of their various forms is highly important as appropriate
      primary and symptomatic management can substantially reduce the morbidity and
      mortality associated with these disorders.

PMID- 15518598
TI  - Magnetic resonance spectroscopic findings in neuro-Behcet disease.
AB  - BACKGROUND: Behcet disease is a heterogeneous, multisystem disorder with elements
      of both environmental and autoimmune pathologic processes. Neuro-Behcet, found in
      10%-25% of Behcet patients, has been characterized as a vasculitis primarily
      affecting the brain stem. On magnetic resonance imaging, some cases demonstrate
      extension to the bilateral cerebral cortices and/or the spinal cord, often with a
      degree of mass effect. Content of this paper provides a case study, along with
      review of the literature regarding this disease entity, and proceeds to outline
      the appearance of neuro-Behcet on magnetic resonance spectroscopy. CONCLUSION: In
      essence, a drop in the N-acetyl aspartate peak indicative of axonal loss in
      concert with elevations in lipid myoinositol and choline/creatine ratios
      (nonspecific markers of myelin breakdown) is found, indicating that a possible
      demyelinating process is complexed with the vasculitic pathology neuro-Behcet is
      traditionally ascribed to.

PMID- 15518599
TI  - Charcot-Marie-Tooth disease (hereditary motor sensory neuropathies) and
      hereditary sensory and autonomic neuropathies.
AB  - BACKGROUND: Since the description of Charcot-Marie-Tooth disease over a century
      ago. it has now been recognized that these conditions are not caused by
      generalized metabolic defects but rather have various discrete genetic origins.
      These disorders can also have variable phenotypes due to dysfunction of
      peripheral nerve axons or their myelin due to the genetic defects that affect the
      formation of specific nerve proteins. REVIEW SUMMARY: This article summarizes the
      clinical presentation of various phenotypes of the hereditary motor sensory
      neuropathies and the hereditary sensory and autonomic neuropathies, genetic
      mutations, and their relevant protein products. Proper identification of the
      genetic defects provides the opportunity for better genetic counseling and
      hopefully therapies in the future.

PMID- 15518600
TI  - Vitamin B12 and folate depletion: clinical evidence in a neurological population.
AB  - In cross-sectional studies, low levels of folate and vitamin B12 have been
      associated with poor cognition and dementia. Results are quite controversial and
      a debate continues in the literature. Still not completely understood are the
      differential roles of folate and vitamin B12 in memory acquisition and cognitive
      development. More intriguing and not fully understood is the rule that treating a
      vitamin B12-deficient patient with folate may exacerbate the neurological
      consequences of either deficiency. Starting from these quite confusing
      perspectives, the aim of this study was to define a possible role of vitamin B12
      and folate in cognitive disruption. Data were collected among a cohort of people,
      admitted to the Neurology Clinic of the University of Trieste, in a period
      between November 1,2000, and November 1, 2002. We examine potential risk factors,
      concomitant drug-therapies, and cognitive global performance and correlate these
      parameters with folate and vitamin B 12 serum levels.We discuss the results with
      an overview of the literature.

PMID- 15518601
TI  - Patient and family fact sheet. Cognitive function in the elderly.

PMID- 15518602
TI  - Early effects of statins in patients with coronary artery disease and high C
      reactive protein.
AB  - Statins improve survival in patients with coronary artery disease, especially
      those with elevated C-reactive protein (CRP). Although some randomized studies
      have shown a delay in statin-related survival advantage of up to 2 years, recent
      studies demonstrated early (<2 months) survival benefit in certain patient
      groups. We hypothesized that this early benefit relates to baseline CRP
      concentration. Patients (n = 2,924) with significant, angiographically defined
      coronary artery disease (>/=70% stenosis in >/=1 coronary artery) were followed
      for an average of 2.4 years after discharged on a statin prescription. CRP was
      divided into tertiles (<1.2, 1.2 to 1.7, >1.7 mg/dl), and Kaplan-Meier methods
      were used to determine timing of statin benefit in both the overall population
      and a propensity score-matched subgroup. Cox regressions (multivariable and
      propensity score approaches) were used to predict mortality. Statins were
      prescribed for 28.4% of patients. In the first CRP tertile, no early statin
      benefit was observed (adjusted hazard ratio 0.69, 95% confidence interval [CI]
      0.30 to 1.6, p = 0.39), and survival curves separated after >2 years. However, in
      the second and the third tertiles, statin survival curves separated much earlier
      ( approximately 3 months and 1 week, respectively) and statins predicted improved
      survival (second tertile: hazard ratio 0.63, 95% CI 0.32 to 1.2, p = 0.17; third
      tertile: hazard ratio 0.35, 95% CI 0.18 to 0.67, p = 0.002). Propensity score
      analysis confirmed both statin benefit and early timing. Thus, statin use in
      patients with high CRP provides not only a larger but also a significantly
      earlier absolute survival benefit than statin use in patients with lower CRP.
      This provides further evidence of an anti-inflammatory effect of statins.

PMID- 15518603
TI  - Sequential risk stratification using TIMI risk score and TIMI flow grade among
      patients treated with fibrinolytic therapy for ST-segment elevation acute
      myocardial infarction.
AB  - In the setting of ST-segment elevation myocardial infarction (STEMI), the
      Thrombolysis In Myocardial Infarction (TIMI) risk score (TRS) and indexes of
      epicardial and myocardial perfusion are associated with mortality. The
      association between TRS at presentation and angiographic indexes of epicardial
      and myocardial perfusion after reperfusion therapy has not been investigated. We
      hypothesized that TRS, TIMI flow grade (TFG), and TIMI myocardial perfusion grade
      (TMPG) would provide independent prognostic information and that angiographic
      indexes of poor flow and perfusion would be associated with a higher TRS. TRS and
      angiographic data were evaluated in 3,801 patients from the TIMI 4, 10A, 10B, 14,
      20, 23, and 24 trials. Within each TRS stratum (TRS 0 to 2, 3 to 4, >/=5), 30-day
      mortality increased stepwise among patients with impaired TFG at 60 minutes after
      fibrinolytic administration. In a multivariate model adjusting for the TRS
      strata, impaired TMPG (0/1) was independently associated with higher mortality
      (odds ratio 2.28, p = 0.018). In a multivariate model adjusting for the TFG and
      infarct location, the likelihood of impaired TMPG (0/1) was greater among
      intermediate-risk (TRS 3 to 4) and high-risk (TRS >/=5) patients than among low
      risk (TRS 0 to 2) patients (odds ratio 1.43, p = 0.019 and 1.50, p = 0.055,
      respectively). Thus, impaired epicardial flow and myocardial perfusion are
      independently associated with increased 30-day mortality among patients
      identified by TRS as high risk, although there is no synergism between either TFG
      or TMPG and TRS. High TRS at presentation is associated with abnormal myocardial
      perfusion, even after adjusting for possible confounders.

PMID- 15518604
TI  - In-hospital management and outcome in women with acute myocardial infarction
      (data from the AMI-Florence Registry).
AB  - Primary percutaneous coronary intervention proved to be superior to thrombolysis
      in reducing ST-segment elevation acute myocardial infarction (STEAMI) mortality.
      However, whether such benefit is similar in women and men remains unclear. The
      aim of the present analysis was to assess the independent effect of female gender
      on management and on early and 1-year mortality in Florence, Italy, where primary
      percutaneous coronary intervention is the preferred reperfusion strategy for
      STEAMI. The study included a cohort of 920 unselected patients with STEAMI (men =
      627, women = 293) prospectively enrolled in the AMI-Florence, population-based
      registry over 12 months. Women were older (76 vs 68 years, p <0.001) and more
      frequently had Killip class >I heart failure than men. The median delay to
      hospital admission was marginally longer in women (160 vs 130 minutes, p = 0.09).
      Coronary reperfusion treatment was performed less often in women (49% vs 58%, p
      <0.013); primary percutaneous coronary intervention was performed more often in
      both genders (90% vs 91%) and with similar median door-to-balloon time (50 vs 45
      minutes, p = 0.44). Both in-hospital (16% vs 8%, p <0.001) and 1-year mortality
      (25% vs 18%, p = 0.016) were higher in women. However, after adjusting for age
      and other baseline characteristics, reperfusion treatment (odds ratio 1.27, 95%
      confidence interval [CI] 0.78 to 2.08) and 1-year mortality (hazard ratio [HR]
      0.91, 95% CI 0.67 to 1.24) were independent of female gender. Compared with
      conservative therapy, reperfusion treatment was associated with a similar
      reduction in 1-year mortality in women (HR 0.59, 95% CI 0.34 to 1.02) and men (HR
      0.58, 95% CI 0.37 to 0.92). Our data suggest that older age and several age
      related factors may largely account for the higher mortality of women after
      STEAMI. Even in the general population,improvement in prognosis associated with
      reperfusion treatment is independent of gender.

PMID- 15518605
TI  - Disparate opinions regarding indications for coronary artery revascularization
      before elective vascular surgery.
AB  - Despite consensus guidelines, the optimal strategy for preoperative cardiac risk
      management among patients scheduled for major noncardiac surgery remains
      controversial. This study assesses current opinion about the role of preoperative
      coronary revascularization for patients with coronary artery disease scheduled
      for elective vascular surgery. Thirty-one practicing cardiologists recruited from
      4 different regions reviewed case records, imaging tests, and coronary angiograms
      of 12 patients with coronary artery disease participating in the Coronary Artery
      Revascularization Prophylaxis (CARP) trial. The need for preoperative coronary
      revascularization was determined and results summarized using 3 categories:
      favoring conservative management, neutral, or recommending revascularization
      (either by percutaneous intervention or bypass surgery). We found recommendations
      were frequently disparate and often deviated from published guidelines (40% of
      the time). The likelihood of discordance between 2 cardiologists was 54%, with a
      26% chance that recommendations for revascularization would be directly
      contradictory. Opinions were more often conservative (43%) or aggressive (40%)
      than neutral (17%). Similar inconsistency was found as to the preferred method of
      revascularization, with only 1 patient having complete agreement. Thus, this
      study reveals substantial differences of opinion among cardiologists across the
      country about the role of preoperative coronary artery revascularization for
      patients scheduled for elective vascular operations. Deviations from published
      guidelines are common, suggesting that current consensus statements need
      additional data to support their recommendations.

PMID- 15518606
TI  - Prognostic value of endocardial electromechanical mapping in patients with left
      ventricular dysfunction undergoing percutaneous coronary intervention.
AB  - Endocardial electromechanical mapping (EEM) has been proposed as a method for
      myocardial viability assessment. However, the impact of EEM data on clinical
      outcome has not been studied before. We sought to assess the prognostic value of
      EEM in patients with left ventricular (LV) dysfunction undergoing percutaneous
      coronary intervention (PCI). Seventy-five patients with coronary artery disease
      and LV dysfunction (angiographic LV ejection fraction [EF] 49 +/- 15%) underwent
      LV EEM for myocardial viability assessment before coronary revascularization. EEM
      parameters included mean unipolar electrographic amplitude, mean local
      shortening, LV volumes, LVEF, number of regions with electrographic amplitudes
      <7.5 mV, number of electromechanical mismatch, and match regions. Cardiac death,
      nonfatal myocardial infarction, nonfatal stroke, and acute heart failure
      requiring hospitalization were defined as clinical events. During a follow-up of
      3.6 +/- 1.8 years, 20 clinical events occurred. Event-free survival after
      coronary revascularization was significantly better in patients with a mean
      unipolar electrographic amplitude of >/=9.5 mV than in patients with a mean
      unipolar electrographic amplitude of <9.5 mV (88% vs 57%; p <0.005). Cox
      regression analysis revealed angiographic LVEF, mean electrographic amplitude,
      number of regions with electrographic amplitudes <7.5 mV, number of
      electromechanical match regions, and EEM EF as univariate predictors of clinical
      events. In a multivariate analysis, angiographic LVEF <40% (hazard ratio 4.78, p
      <0.005) and mean electrographic amplitude <9.5 mV (hazard ratio 2.92, p <0.05)
      were independent predictors of clinical events. Thus, EEM provides prognostic
      information in patients with LV dysfunction undergoing coronary
      revascularization.

PMID- 15518607
TI  - Effectiveness and safety of the Proxis system in demonstrating retrograde
      coronary blood flow during proximal occlusion and in capturing embolic material.
AB  - The Feasibility And Safety Trial for its embolic protection device during
      transluminal intervention in coronary vessels: a European Registry (FASTER) was
      designed to demonstrate that (1) the Proxis embolic protection system can control
      anterograde flow and reverse blood flow in native coronary arteries and saphenous
      vein grafts; and (2) this system can capture embolic debris. Percutaneous
      coronary intervention on stenotic coronary lesions revolutionized treatment of
      coronary disease, but is associated with the risk of major adverse cardiac
      events. This prospective, nonrandomized, multicenter clinical feasibility and
      safety study enrolled 40 patients with 51 lesions at 4 centers who underwent
      treatment of stenotic lesions with proximal emboli protection (Proxis system).
      Proxis was successfully used 95% of the time, and embolic debris was
      qualitatively identified in all cases. Major adverse cardiac events occurred in 2
      patients (5.0%): 1 late in-stent thrombosis resulting in death and 1 non-Q-wave
      infarction when a lesion was crossed before deployment of the Proxis system. Mean
      vessel occlusion time was 4.3 +/- 2.4 minutes. Native flow reversal was
      sufficient in 31 patients, with a mean aspirate volume of 11.8 +/- 6.5 ml. When
      the infusion catheter was used to augment reflow, mean occlusion time was 4.6
      minutes. In conclusion, this trial is the first to demonstrate that retrograde
      blood flow can be achieved during proximal occlusion and that the Proxis system
      can be used safely during intervention of saphenous vein grafts and native
      coronary arterial lesions to capture embolic material.

PMID- 15518608
TI  - Comparative pharmacokinetic interaction profiles of pravastatin, simvastatin, and
      atorvastatin when coadministered with cytochrome P450 inhibitors.
AB  - Three-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors (statins) are
      first-line treatments for hypercholesterolemia. Although exceedingly well
      tolerated, treatment with statins incurs a small risk of myopathy or potentially
      fatal rhabdomyolysis, particularly when coadministered with medications that
      increase their systemic exposure. Studies compared the multiple-dose
      pharmacokinetic interaction profiles of pravastatin, simvastatin, and
      atorvastatin when coadministered with 4 inhibitors of cytochrome P450-3A4
      isoenzymes in healthy subjects. Compared with pravastatin alone, coadministration
      of verapamil, mibefradil, or itraconazole with pravastatin was associated with no
      significant changes in pravastatin pharmacokinetics. However, concomitant
      verapamil increased the simvastatin area under the concentration:time curve (AUC)
      approximately fourfold, the maximum serum concentration (C(max)) fivefold, and
      the active metabolite simvastatin acid AUC and C(max) approximately four- and
      threefold, respectively (all comparisons p <0.001). Similar (greater than
      fourfold) important increases in these parameters and a >60% increase in the
      serum half-life (p = 0.03) of atorvastatin were observed when coadministered with
      mibefradil. The half-life of atorvastatin also increased by approximately 60% (p
      = 0.052) when coadministered with itraconazole, which elicited a 2.4-fold
      increase in the C(max) of atorvastatin and a 47% increase in the AUC (p <0.001
      for C(max) and AUC). Clarithromycin significantly (p <0.001) increased the AUC
      (and C(max)) of all 3 statins, most markedly simvastatin ( approximately 10-fold
      increase in AUC) and simvastatin acid (12-fold), followed by atorvastatin
      (greater than fourfold) and then pravastatin (almost twofold). Pravastatin has a
      neutral drug interaction profile relative to cytochrome P450-3A4 inhibitors, but
      these substrates markedly increase systemic exposure to simvastatin and
      atorvastatin.

PMID- 15518609
TI  - Gender and risk of adverse outcomes in heart failure.
AB  - Congestive heart failure (CHF) is the leading cause of hospitalization in the
      elderly, and these patients are at high risk for subsequent hospitalization.
      Whether gender affects the risk of rehospitalization in patients who have CHF is
      less well understood. We studied a random sample of 1,700 adults who had been
      hospitalized with CHF (from July 1, 1999 to June 30, 2000) and identified all
      readmissions through June 30, 2001. We used proportional hazards regression to
      evaluate whether gender affects the risk of all-cause and CHF-specific
      rehospitalization, after adjusting for differences in demographic
      characteristics, health-related behaviors, co-morbid conditions, left ventricular
      systolic function status, and use of CHF therapies. Among 1,591 adults who had
      confirmed CHF, 752 were women (47.3%). Women were older than men (73 vs 71 years,
      p <0.001) and more likely to have preserved systolic function (55.3% vs 40.9%, p
      <0.001), hypertension (83.1% vs 75.2%, p <0.001), and prior renal insufficiency
      (46.8% vs 34.6%, p <0.001). No significant differences existed between women and
      men with respect to crude rates of any readmission (144.7 vs 134.6 per 100 person
      years, p = 0.36) or CHF-specific readmission (39.9 vs 37.4 per 100 person-years,
      p = 0.65). After adjusting for potential confounders, there was no significant
      difference between women and men with respect to risk of any readmission
      (adjusted hazard ratio 0.88, 95% confidence interval 0.76 to 1.02) or readmission
      for CHF (adjusted hazard ratio 0.89, 95% confidence interval 0.71 to 1.11). Among
      a contemporary, diverse population of patients who had CHF, rates of readmission
      overall and for CHF remained high, but gender was not independently associated
      with a differential risk of readmission.

PMID- 15518610
TI  - Importance of in-hospital initiation of evidence-based medical therapies for
      heart failure-a review.
AB  - Patients who have had heart failure (HF) face very high risks of hospitalization
      and mortality. Despite the compelling scientific evidence that angiotensin
      converting enzyme inhibitors, aldosterone antagonists, and beta blockers decrease
      rates of hospitalization and mortality in patients who have had HF, these life
      prolonging therapies continue to be underused. Many studies in a variety of
      clinical settings have documented that important numbers of patients who have had
      HF are not receiving treatment with these evidence-based therapies, which are
      recommended by national guidelines, when guided by conventional care. This HF
      treatment gap results from a variety of complex issues, including lack of systems
      and disease management programs. This gap in beta-blocker therapy may be due in
      part to persisting perceptions, despite recent evidence to the contrary, that it
      should be delayed until patients who developed HF have been stable for 2 to 4
      weeks after hospital discharge and that its initiation results in a substantial
      risk of worsening HF. Conversely, recent clinical trial evidence has
      substantiated that beta blockers can be safely initiated for patients with HF in
      the hospital and that there are early benefits, including decreased risks of
      mortality and hospitalization for worsening HF. It has become increasingly
      evident that in-hospital initiation of evidence-based cardiovascular therapies
      and patient education have a positive effect on long-term patient compliance and
      clinical outcomes. Adopting in-hospital initiation of these therapies as the
      standard of care (in the absence of contraindications or intolerance) in patients
      who have HF and stabilized systolic dysfunction could substantially improve
      treatment rates, decrease the risk of future hospitalizations, and prolong life
      in the large number of patients who are hospitalized each year for HF.

PMID- 15518611
TI  - Short-term (28 days) prognosis between genders according to the type of coronary
      event (Q-wave versus non-Q-wave acute myocardial infarction versus unstable
      angina pectoris).
AB  - The type of acute coronary syndrome may account for different prognoses between
      men and women after myocardial infarction. This study assessed gender differences
      in 28-day mortality rates for first or recurrent Q-wave and non-Q-wave myocardial
      infarctions and unstable angina by using data from 5 registries that included
      20,836 patients (24.8% women). Mortality rates were higher in women with first Q
      wave myocardial infarction but not in the other patients after adjusting for
      confounding variables.

PMID- 15518612
TI  - Comparison of outcomes in acute coronary syndrome in patients receiving statins
      within 24 hours of onset versus at later times.
AB  - The clinical benefits of statins in acute coronary syndromes are well
      established, but the optimal time for administration in this setting has not been
      well studied. In this study, patients who had acute coronary syndrome and
      received statins <24 hours of presentation had lower incidences of death, stroke,
      reinfarction, heart failure, and pulmonary edema compared with delayed
      administration. Prompt administration of statins appears to be significantly
      beneficial in patients who present with an acute coronary syndrome.

PMID- 15518613
TI  - New electrocardiographic criteria for identifying the culprit artery in inferior
      wall acute myocardial infarction-usefulness of T-wave amplitude ratio in leads
      II/III and T-wave polarity in the right V5 lead.
AB  - ST-segment elevations in the right ventricular lead and those greater in lead III
      than in lead II strongly suggest that right, rather than left circumflex,
      coronary arterial occlusion occurs in acute myocardial infarction in the inferior
      wall. Our study demonstrated that, in the very early stages of infarction, a T
      wave amplitude that is greater in lead III than in lead II and an upright or
      positive biphasic T wave in lead V(5)R are just as predictive as ST-segment
      changes and are often easier to measure.

PMID- 15518614
TI  - Class effect of angiotensin-converting enzyme inhibitors on prevention of
      myocardial infarction.
AB  - Angiotensin-converting enzyme (ACE) inhibitors differ in their affinity for
      tissue-bound ACE. It has been hypothesized that tissue ACE affinity might be
      responsible for some of the beneficial cardiovascular properties of ACE
      inhibitors. The present study examined this question and found no correlation
      between tissue ACE affinity and risk of first nonfatal myocardial infarction in
      patients who have hypertension.

PMID- 15518615
TI  - Comparison of the risk of vascular complications associated with femoral and
      radial access coronary catheterization procedures in obese versus nonobese
      patients.
AB  - In this retrospective review of 5,234 cardiac catheterizations and percutaneous
      coronary interventions, the rate of vascular complications was highest in
      extremely thin and morbidly obese patients and lowest in moderately obese
      patients, consistent with the previously reported "obesity paradox." The use of
      transradial access and arterial access closure devices was associated with
      reduced vascular complications in the population of obese patients.

PMID- 15518616
TI  - Comparison of transradial and transfemoral approaches for coronary angiography
      and angioplasty in octogenarians (the OCTOPLUS study).
AB  - This prospective multicenter study was conducted to compare the incidence of
      significant vascular complications delaying hospital discharge after coronary
      angiography and percutaneous coronary intervention (PCI) between the radial
      approach (n = 192) and the femoral approach (n = 185) in octogenarians, a rapidly
      growing population with numerous risk factors for complications. By intention-to
      treat analysis, the incidence of vascular complications was found to be
      significantly less in the radial group (1.6% vs 6.5%, p = 0.03), without any
      decrease in the efficacy of PCI and only a slight increase in procedure duration
      for coronary angiography. All vascular complications, except for 1, occurred in
      patients treated with the transfemoral approach.

PMID- 15518617
TI  - Combined effects of smoking and hypercholesterolemia on inflammatory process,
      thrombosis/fibrinolysis system, and forearm hyperemic response.
AB  - The combined effects of smoking and hypercholesterolemia on the inflammatory
      process, the thrombosis/fibrinolysis system, and forearm hyperemic response were
      investigated. It was shown that smokers with hypercholesterolemia (n = 25) had a
      reduced and delayed forearm hyperemic response compared with healthy smokers (n =
      24), patients with hypercholesterolemia (n = 26), and healthy controls (n = 75; p
      <0.01 for all). This phenomenon was associated with a respective increase in the
      inflammatory process and changes in the thrombosis/fibrinolysis system.

PMID- 15518618
TI  - Flecainide and propafenone induced ST-segment elevation in patients with atrial
      fibrillation: clue to specificity of Brugada-type electrocardiographic changes.
AB  - Potent sodium channel, blockade with type IC antiarrhythmics can provoke
      characteristic electrocardiographic changes consistent with Brugada's syndrome in
      unselected patients with atrial fibrillation. In 176 treated patients, the
      incidence of the characteristic abnormality is small (2.3%), and thus although no
      ventricular arrhythmia events were observed during follow-up, the long-term
      clinical significance in a larger patient cohort remains to be determined. These
      data provide insight into the specificity of the response to type I drug
      administration in patients suspected of having Brugada's syndrome.

PMID- 15518619
TI  - Prevalence and time of appearance of Brugada electrocardiographic pattern in
      young male adolescents from a three-year follow-up study.
AB  - The prevalence of Brugada's electrocardiographic (ECG) pattern in 7,022 male
      adolescents in the seventh grade was determined, and the same subjects were
      reexamined 3 years later, while in tenth grade. Two subjects (0.03%) and 7
      subjects (0.10%) showed Brugada's ECG pattern by the conventional criterion (J
      point or ST-segment >/=0.1 mV in leads V(1) to V(3)), and no subjects (0%) and 2
      subjects (0.03%) fulfilled the recent criterion (J point or ST-segment >/=0.2 mV)
      in the seventh and tenth grades, respectively, indicating that Brugada's ECG
      pattern begins to appear during junior high school and increases until late
      adulthood.

PMID- 15518620
TI  - Usefulness of pindolol for treatment of neurocardiogenic syncope.
AB  - This study evaluated the efficacy of pindolol, a noncardioselective beta blocker
      with intrinsic sympathetic activity, on neurocardiogenic syncope using a head-up
      tilt-table test in 66 patients. Pindolol was equally effective in men and women
      and the 2 age groups (>60 and <60 years) of the study cohort. The earliest
      benefit was seen </=3 days after initiating treatment. Side effects were better
      tolerated in younger patients (age <60 years).

PMID- 15518621
TI  - Time intervals of cardiac resynchronization therapy in heart failure.
AB  - Systolic and diastolic time intervals were measured in 11 patients with heart
      failure before and 1 and 3 months after the placement of atrial biventricular
      pacemakers for cardiac resynchronization therapy (CRT). CRT shortened the
      preejection period, principally by reducing left ventricular (LV)
      electromechanical delay with lesser reduction of isovolumic contraction time, and
      shortened the duration of LV systole, with a consequent trend of lengthening
      diastolic time.

PMID- 15518622
TI  - Relation of calcium-phosphorus product to the severity of aortic stenosis in
      patients with normal renal function.
AB  - Calcium-phosphorus product (CaxP) has been associated with severity of aortic
      stenosis (AS) in dialysis patients, but it is unknown whether a relation exists
      in patients with normal renal function. One hundred seven patients with AS and
      normal serum creatinine were studied to determine whether there was an
      association between CaxP and AS severity, and it was found that CaxP was
      inversely related to AS severity, as measured by aortic valve area and
      transvalvular gradients.

PMID- 15518623
TI  - Role of troponin I in active infective endocarditis.
AB  - Infective endocarditis (IE) remains a disease associated with high morbidity and
      mortality rates. In this pilot study, the role of troponin I in IE was assessed.
      Myocardial involvement distal to the site of infection in IE has been previously
      described. Elevated troponin was demonstrated in 11 of 15 patients diagnosed with
      the condition. Patients diagnosed with staphylococcal endocarditis were more
      likely to have elevated troponin (3 of 3 patients). Patients with elevated
      troponin I were not more likely to need valve replacement. Troponin I levels did
      not predict perivalvular extension. It is hypothesized that elevated troponin I
      is a reflection of myocardial involvement.

PMID- 15518624
TI  - Development of exercise-induced arm-leg blood pressure gradient and abnormal
      arterial compliance in patients with repaired coarctation of the aorta.
AB  - Often, the lack of systemic arterial hypertension and the lack of a resting arm
      leg blood pressure gradient are used to assess the adequacy of the anatomic
      result after intervention for coarctation of the aorta (CoA). Some patients with
      no arm-leg gradient at rest may develop a gradient with exercise, leading
      caregivers to question the success of the repair. It is not clear what the
      prevalence is of patients who have undergone a successful intervention for CoA
      and have no arm-leg gradient at rest but develop a significant gradient with
      exercise and which factors may predict the development of an arm-leg gradient
      with exercise. This study evaluates the prevalence and predictors of an exercise
      induced arm-leg gradient in subjects who have undergone an apparently successful
      intervention for CoA.

PMID- 15518625
TI  - Analysis of right ventricular Doppler tissue imaging and load dependence in
      patients undergoing percutaneous closure of atrial septal defect.
AB  - In patients with volume overload due to atrial septal defect (ASD) and Doppler
      tissue imaging E'/A' <1 at baseline, right ventricular (RV) myocardial velocities
      show load independence after closure with a device. Conversely, in patients with
      ASD with basal E'/A' >1, regional velocities are load-dependent and positively
      correlate with RV dimension. Because RV Doppler tissue imaging velocities are
      still in the normal range 1 month after ASD closure, cardiac function does not
      seem to be affected by the presence of the occluder device.

PMID- 15518626
TI  - Effect of HMR 3339, a novel selective estrogen receptor modulator, on C-reactive
      protein levels in healthy postmenopausal women.
AB  - We investigated the 12-week effects of 3 doses of HMR 3339, a novel selective
      estrogen receptor modulator, in comparison with raloxifene and placebo, on plasma
      concentrations of C-reactive protein in 96 healthy postmenopausal women. A dose
      dependent reduction in C-reactive protein was observed, the largest reduction
      with HMR 3339 50 mg.

PMID- 15518627
TI  - Effect of preload reduction by hemodialysis on left atrial volume and
      echocardiographic Doppler parameters in patients with end-stage renal disease.
AB  - Left atrial (LA) volume has been proposed as a less preload-dependent parameter
      of diastolic function than Doppler mitral inflow. We hypothesize that in the
      absence of mitral regurgitation and atrial fibrilation, LA enlargement could be a
      more practical (and relatively preload-independent) method for the evaluation of
      left ventricular diastolic function. The aim of the present study was to
      determine the effects of preload reduction by hemodialysis on LA volume.

PMID- 15518628
TI  - Racial differences in aortic atheroma in patients undergoing transesophageal
      echocardiography for unexplained stroke or transient ischemic attack.
AB  - Racial differences in the prevalence of complex thoracic aortic atheroma were
      evaluated in 318 patients referred for transesophageal echocardiography after
      unexplained stroke or transient ischemic attack. African-Americans were found to
      have fewer complex thoracic aortic atheroma and fewer combined cardiac sources of
      embolus than Caucasian patients. This finding persists after adjusting for racial
      differences in atherosclerotic risk factors.

PMID- 15518629
TI  - Isolated noncompaction involving the left ventricular apex in adults.
AB  - We present a series of 9 adults in 2 families with isolated noncompaction of the
      ventricular myocardium involving the left ventricular apex. Three of these
      patients had been previously misdiagnosed as having dilated cardiomyopathy,
      apical hypertrophic cardiomyopathy, or apical mural thrombus. Phenotypic
      variation was observed with gradation of severity of noncompaction and left
      ventricular systolic dysfunction between first-degree relatives.

PMID- 15518630
TI  - Resting and ambulatory heart rate variability in chronic anorexia nervosa.
AB  - Heart rate variability was measured at rest and during ambulation in 6 women with
      anorexia nervosa. Compared with 10 nonanorexic women controls, resting and
      ambulatory measures of heart rate variability tended to be lower in patients,
      despite no differences in resting heart rate.

PMID- 15518631
TI  - The Amish, body weight, and exercise.

PMID- 15518632
TI  - Reporting measures of endothelial dysfunction independent of baseline arterial
      diameter.

PMID- 15518633
TI  - Will green tea be even better than black tea to increase coronary flow velocity
      reserve?

PMID- 15518634
TI  - Pacing for heart block after septal reduction therapy.

PMID- 15518635
TI  - Effect of Vigabatrin on motor responses to transcranial magnetic stimulation: an
      effective tool to investigate in vivo GABAergic cortical inhibition in humans.
AB  - In this study, transcranial magnetic stimulation (TMS) of the hand primary motor
      area was used to test possible excitability changes induced by the administration
      of Vigabatrin (Gamma-Vinyl-gamma-aminobutryic acid;4-amino-hex-5-enoic acid;
      GVG), a selective GABAergic drug, on cortical inhibitory mechanisms in healthy
      subjects. In a group of 15 healthy volunteers, the level of motor cortical
      excitability was studied by means of paired-pulse TMS (p-TMS) protocols exploring
      the early (1-6 ms of interstimulus intervals, ISI) and the late cortical
      inhibition (20-250 ms ISI), and by evaluating the cortical silent period (CSP)
      duration obtained in response to single pulse stimulation of cortical motor area.
      In all participants TMS procedures were carried out before and after
      administering GVG for three consecutive days at a daily dosage of 50 mg/kg. Three
      months later, a third TMS recording session was repeated to investigate possible
      long-lasting GVG effects on cortical excitability. GVG induces relevant changes
      of cortical excitability consisting in an increase of late cortical inhibition in
      response to the long ISI p-TMS and in a prolonged duration of the CSP. No
      significant change in the early cortical inhibition was observed in response to
      the short ISI p-TMS. The analysis of peripheral motor excitability was also
      assessed, with no effects. The present electrophysiological data show that GVG is
      able to induce a significant increase of the late cortical inhibition, whereas it
      does not affect the early cortical inhibition. These data suggest that the great
      availability of synaptic GABA differently acts on the inhibitory circuitries
      controlled by different GABA-receptor subtypes.

PMID- 15518636
TI  - Oral administration of an AT1 receptor antagonist prevents the central effects of
      angiotensin II in spontaneously hypertensive rats.
AB  - Peripheral and brain angiotensin II AT(1) receptor blockade decreases high blood
      pressure, stress, and neuronal injury. To clarify the effects of long-term brain
      Ang II receptor blockade, the AT(1) blocker, candesartan, was orally administered
      to spontaneously hypertensive rats (SHRs) for 40 days, followed by
      intraventricular injection of 25 ng of Ang II. Before Ang II injection, AT(1)
      receptor blockade normalized blood pressure and decreased plasma
      adrenocorticotropic hormone (ACTH) and corticosterone. After central
      administration of excess Ang II, the reduction of ACTH and corticosterone release
      induced by AT(1) receptor blockade no longer occurred. Central Ang II
      administration to vehicle-treated SHRs further increased blood pressure, provoked
      drinking, increased tyrosine hydroxylase (TH) mRNA expression in the locus
      coeruleus, and stimulated sympathoadrenal catecholamine release. Pretreatment
      with the AT(1) receptor antagonist eliminated Ang II-induced increases in blood
      pressure, water intake, and sympathoadrenal catecholamine release; inhibited
      peripheral and brain AT(1) receptors; increased AT(2) receptor binding in the
      locus coeruleus, inferior olive, and adrenal cortex; and decreased AT(2) receptor
      binding in the adrenal medulla. Inhibition of brain AT(1) receptors correlated
      with decreased TH transcription in the locus coeruleus, indicating a decreased
      central sympathetic drive. This, and the diminished adrenomedullary AT(1) and
      AT(2) receptor stimulation, result in decreased sympathoadrenomedullary
      stimulation. Oral administration of AT(1) antagonists can effectively block
      central actions of Ang II, regulating blood pressure and reaction to stress, and
      selectively and differentially modulating sympathoadrenal response and the
      hypothalamic-pituitary-adrenal stimulation produced by brain Ang II--effects of
      potential therapeutic importance.

PMID- 15518637
TI  - Absence of localized grey matter volume changes in the motor cortex following
      spinal cord injury.
AB  - The consequences of spinal cord injury (SCI) have considerable effects on motor
      function, typically resulting in functional impairment. Pathological changes have
      been studied at the site of trauma, rostrocaudally within the cord, and in the
      periphery. Few studies, however, have investigated the consequences of SCI at the
      cortical level. Magnetic resonance imaging (MRI) was used to explore the
      morphological changes in the grey and white matter within the primary motor (M1)
      cortex of individuals with cervical SCI. The "precentral knob," a landmark of M1
      cortex dedicated to hand function, was selected for regionally specific
      measurements of change. Thirty-one hemispheres of SCI subjects and 28 hemispheres
      of control subjects were compared using a manual measurement after the images
      were segmented into grey matter, white matter, and cerebral spinal fluid (CSF).
      No significant differences in grey matter area measured at the precentral knob
      were found with the manual approach. An automated voxel-based morphometric
      analysis was also performed and demonstrated no significant differences in grey
      or white matter volume within an M1 region of interest. These data suggest that
      there is no gross anatomical change within M1 following cervical SCI. Our
      previously reported findings of reorganization of cortical motor output maps
      following SCI therefore likely result from changes in functional organization
      rather than anatomical changes.

PMID- 15518638
TI  - Fatigue in a simple repetitive motor task: a combined electrophysiological and
      neuropsychological study.
AB  - Fatigue is one of the most common psychophysiological symptoms that interact with
      the control mechanisms regulating task behaviour. The cortical processes involved
      in preparation and feedback control of voluntary movement are associated with EEG
      activity time-locked to movement onset: a pre-movement Movement-Related Cortical
      Potential (MRCP) is followed by a post-movement potential (PMP). The aim of this
      study was to determine whether changes in subjective fatigue which arise in the
      course of a simple repetitive motor task affect cortical information processing
      as measured by MRCPs or PMPs. MRCPs/PMPs were recorded in 33 healthy subjects
      while they made 100 self-paced unilateral button presses with their left or right
      index finger, and then continued with the other index finger for another 100
      movements. Before and after the motor tasks, subjective fatigue was assessed via
      questionnaire. (1) Subjects who reported a higher increase of fatigue when they
      had finished the motor tasks showed smaller (more negative) amplitudes of the
      PMP. (2) This increase of negativity was strongest during the initial part of the
      tasks. (3) Physical aspects of perceived fatigue had a stronger effect on PMP
      amplitude than cognitive aspects. Smaller amplitudes of the PMP in more fatigued
      subjects might be explained by reduced attention to somatosensory feedback.
      Adaptation of this effect may result from more automatic performance at later
      stages of the task when all subjects required a lower degree of attentional
      control. In conjunction with previous studies, effects of fatigue could be
      separated from habituation.

PMID- 15518639
TI  - The thalamic intergeniculate leaflet modulates photoperiod responsiveness in
      Siberian hamsters.
AB  - Siberian hamsters are seasonal breeders that use changes in day length to
      synchronize their reproductive effort with those times of the year most favorable
      for successful reproduction. The ability of Siberian hamsters to measure and
      respond to changes in day length depends upon accurate photoentrainment of the
      circadian clock in the suprachiasmatic nucleus (SCN) of the hypothalamus. Two
      pathways have been characterized through which entraining stimuli reach the SCN:
      the retinohypothalamic tract (RHT), which transmits light information from the
      retinae, and the geniculohypothalamic tract (GHT) from the intergeniculate
      leaflet of the thalamus (IGL), which is involved in transmitting both photic and
      nonphotic cues. Ablating the IGL/GHT results in only modest alterations in
      entrainment to static day lengths and fails to interfere with seasonal responses
      induced by transfer from static long day to static short day lengths. Because
      several studies suggest that the IGL may be involved in tracking the time of dusk
      and dawn, we sought to determine whether an intact IGL is necessary for hamsters
      to respond to a simulated natural photoperiod (SNP) in which the time of dusk and
      dawn gradually changes in a pattern approximating the rate of change in day
      length that occurs during autumn at the latitude this species inhabits in nature.
      The results indicate that neurochemical lesions of the IGL alter both the pattern
      of circadian entrainment and photoperiodic responsiveness of Siberian hamsters to
      an SNP. Both intact and IGL-lesioned hamsters exhibited testicular regression in
      shortening day lengths, but only IGL-intact hamsters exhibited seasonal pelage
      molt.

PMID- 15518640
TI  - Microinjection of bicuculline into the central nucleus of the amygdala alters
      gustatory responses of the rat parabrachial nucleus.
AB  - The central amygdaloid nucleus (CeA) receives projection from the parabrachial
      nucleus (PBN) gustatory neurons and descendingly projects to the PBN, and taste
      responses in the PBN are significantly affected by stimulation or lesion of the
      CeA. To examine whether the GABA receptors within the CeA are involved in this
      modulation, the effects of microinjection of bicuculline, a GABA(A)-selective
      antagonist, into the CeA on the activities of PBN taste neurons were observed by
      using extracellular recording technique. In general, after bicuculline was
      administered to ipsilateral CeA, the responses of PBN neurons to four tastants
      all increased, with the magnitudes significantly higher than those obtained
      before drug administration (P<0.01), respectively. However, after bicuculline was
      delivered into the contralateral CeA, only the responses to NaCl, HCl and QHCl
      increased. According to the best-stimulus category, 47% NaCl-best (8/17), 64% HCl
      best (7/11), 80% QHCl-best (4/5), and 33% sucrose-best (1/3) increased their
      responses to at least one basic taste stimulus after GABA(A) receptors within the
      ipsilateral CeA were blocked. After contralteral CeA injection, more NaCl-best
      neurons (6/8) increased responses than that after ipsilateral CeA injection, but
      other best-stimulus units showed no differences before and after drug injection
      into the contralateral CeA. Analyses of across-unit patterns indicated that the
      correlation coefficient of responses between NaCl and sucrose was apparently
      higher after drug administration to the CeA. However, after drug injection into
      the contralateral CeA, the correlations between NaCl and the other three tastants
      were higher than those before. These results indicate that the GABA(A) receptors
      within the CeA play an important role in modulating the gustatory activities of
      PBN neurons.

PMID- 15518641
TI  - Role of central 5-HT3 receptors in the control of blood pressure in stressed and
      non-stressed rats.
AB  - The aim of the present study was to investigate the participation of central 5
      HT(3) receptors in the control of blood pressure and heart rate (HR) of non
      stressed and stressed rats. The pharmacological stimulation of brain 5-HT(3)
      receptors by third ventricle injections of the selective 5-HT(3) receptor agonist
      m-CPBG induced a significant decrease in blood pressure in non-stressed rats and
      impaired the hypertensive response induced by restraint stress. The blockade of
      brain 5-HT(3) receptors by the central administration of the selective 5-HT(3)
      antagonist ondansetron elicited a significant increase in blood pressure in non
      stressed rats. Conversely, the hypertensive response induced by restraint stress
      was not affected by central administration of ondansetron. Additionally,
      baroreflex-mediated bradycardia during phenylephrine-induced hypertensive
      response was preserved in non-stressed animals receiving third ventricle
      injections of m-CPBG, while the baroreflex-mediated tachycardia that occurs
      during the hypotensive response induced by the administration of sodium
      nitroprusside was impaired. It is concluded that the serotoninergic component
      represented by the brain 5-HT(3) receptors exerts a tonic inhibitory influence on
      the central control of blood pressure in non-stressed rats, probably by a
      sympathoinhibitory-related mechanism. On the other hand, during stress, this
      central 5-HT(3)-dependent inhibitory drive is overwhelmed by the different
      neurochemical systems that harmonically trigger and sustain the hypertensive
      response.

PMID- 15518642
TI  - Antisense oligonucleotide against GTPase Rab5b inhibits metabotropic agonist DHPG
      induced neuroprotection.
AB  - (S)-3,5-dihydroxyphenylglycine (DHPG), a group I metabotropic glutamate receptor
      (mGluR1 and 5) agonist reduced NMDA-mediated membrane currents, NMDA-induced cell
      death and up-regulated Rab5b, a small GTPase involved in endocytosis [M.
      Blaabjerg, A. Baskys, J. Zimmer and M. P. Vawter, Changes in hippocampal gene
      expression after neuroprotective activation of group I metabotropic glutamate
      receptors, Molec. Brain Res. 117 (2003) 196-205; M. Blaabjerg, L. Fang, J. Zimmer
      and A. Baskys, Neuroprotection against NMDA excitotoxicity by group I
      metabotropic glutamate receptors is associated with reduction of NMDA stimulated
      currents, Experimental Neurol. 183 (2003) 573-580.]. To examine the role of Rab5b
      on DHPG-mediated neuroprotection in organotypic hippocampal cultures, we
      developed antisense oligonucleotide targeted to suppress Rab5b translation.
      Treatment of cultures with the antisense (24 h) but not scrambled sequence
      oligonucleotide suppressed DHPG-induced increase in Rab5b expression and
      significantly disrupted DHPG-induced protection against NMDA toxicity in a
      concentration-dependent manner (0.01-10 nM). Antisense but not scrambled
      oligonucleotide treatment reduced NMDA toxicity (to 74.4+/-5.9% of control) and
      this effect could be blocked by protein kinase C inhibitor staurosporine (0.2
      microM) or with the protease inhibitor leupeptin (100 microM). Application of
      osmotic shock followed by K(+) depletion to disrupt endocytosis abolished the
      protective effect of DHPG. These data suggest that neuroprotection by DHPG
      against NMDA-mediated injury may involve facilitation of NMDA receptor
      endocytosis likely stimulated by DHPG-induced increase in Rab5b synthesis.

PMID- 15518643
TI  - In the adult CNS, ethanol prevents rather than produces NMDA antagonist-induced
      neurotoxicity.
AB  - Single doses of an NMDA antagonist cause an adult or a prepubertal form of
      neurodegeneration, depending on the age of the animal. Single doses of ethanol
      (EtOH) by blocking NMDA receptors produce apoptotic neurodegeneration in young
      animals. This capability could account, in part, for the ability of EtOH to
      produce the fetal alcohol syndrome. We investigated whether EtOH could produce
      NMDA antagonist-induced neurotoxicity (NAN), a different neurotoxicity that is
      seen only in adult animals. In spite of producing blood EtOH levels (30 to 600
      mg/dl) known to block NMDA receptors, EtOH was unable to produce neurotoxicity in
      the adult central nervous system (CNS). Moreover, EtOH in a dose-dependent
      fashion (ED(50)=138 mg/dl) prevented the selective and powerful NMDA antagonist,
      MK-801, from producing NAN in adult animals, suggesting that activity at another
      site might be negating the neurotoxic effect of EtOH's inherent NMDA antagonistic
      activity. Because GABA(A) agonism and non-NMDA glutamate antagonism, properties
      which EtOH possesses, can prevent NAN, we proceeded to study whether GABA(A)
      antagonists (or agents capable of reversing EtOH's GABAergic effects) and non
      NMDA agonists could reverse EtOH's protective effect. Bicuculline, Ro15-4513,
      finasteride, kainic acid or AMPA, alone or in combination, did not significantly
      reverse EtOH's protective effect. Given that EtOH has effects on a wide range of
      ion channels and receptors, determining the precise mechanism of EtOH's
      protective effect will take additional effort. The inability of EtOH to acutely
      produce NAN in the adult CNS indicates that, in contrast to fetuses, brief
      exposure of the adult CNS to EtOH is non-toxic for neurons.

PMID- 15518644
TI  - Contrasting grooming phenotypes in C57Bl/6 and 129S1/SvImJ mice.
AB  - Since C57 and 129 mice are the commonly used background strains, a better
      knowledge of all their behavioural characteristics is important in neuroscience
      research. Grooming is a complex and essential ritual in the rodent behavioural
      repertoire, normally proceeding in a cephalocaudal progression (paws-nose-face
      body-legs-tail and genitals). Various stressors as well as genetic manipulations
      have been reported to alter mouse grooming and its patterning, underlying the
      importance of analysis of grooming behaviours in detail. Although strain
      differences between C57BL/6 and 129S1/SvImJ substrains have been assessed in many
      studies, no ethological analyses of their grooming have been performed. Here we
      show strain differences between these mice in spontaneous (novelty-induced) and
      artificial (water-induced) grooming. Overall, 129S1/SvImJ mice demonstrated less
      grooming activity, more interrupted and incomplete bouts, and more incorrect
      transitions (contrary to the cephalocaudal rule) between patterns, accompanied by
      lower vertical activity and higher defecation/urination in both tests. These
      results are consistent with general hypoactive anxious phenotype in 129S1/SvImJ
      mice and suggest that ethological analysis of mouse grooming may be used in
      neurobehavioural stress research, including behavioural phenotyping of both
      mutant and background mice.

PMID- 15518645
TI  - Inhomogeneous propagation of cortical spreading depression-detection by electro-
      and magnetoencephalography in rats.
AB  - Spreading depression (SD) propagates in cortical regions that are different in
      their morphological and functional characteristics. We tested whether the
      propagation pattern of spreading depression was different between parts of the
      cortex. In six adult rats, we recorded the ECoG by a 4 x 4 electrode array that
      covered parts of the frontal, parietal cortex and the cingulate cortex.
      Simultaneously a 16-channel magnetoencephalogram was recorded to characterize the
      development and direction of intracortical ion movements accompanying this
      phenomenon. Spreading depression was initiated by occipital application of 0.3
      molar KCl solution. Depolarization was observed, at first, at lateral cortical
      regions and then at medial cortical regions. Thereafter, the propagation velocity
      increased in medial cortical regions and was faster than in lateral regions.
      Negative potential shifts were detected by all electrodes, but the depolarization
      reached a maximum over lateral and caudal cortical regions. The recorded magnetic
      fields indicated the same orientation of currents underlying these fields, which
      was perpendicular to the wave front and points away from the depolarization
      region. Overall, the data indicated that propagation patterns of spreading
      depression differed between parts of the cortex and, thus, propagation was
      inhomogeneous. This propagation was accompanied by strong currents parallel to
      the cortical surface.

PMID- 15518646
TI  - Altered expression of BDNF and its high-affinity receptor TrkB in response to
      complex motor learning and moderate exercise.
AB  - We report that rats learning complex motor skills or exercising moderately show
      changes in expression of brain-derived neurotrophic factor (BDNF) and its
      receptor, TrkB protein, in cerebellum and motor cortex. It is now known that
      physical activity increases expression of some neurotrophins. We examined the
      time course of BDNF and TrkB expression after 1, 3, 5, 7 or 14 days in one of
      three conditions: (1) an "acrobatic" motor skill learning condition (AC), (2) a
      motor activity condition (moderately paced running on a flat track; MC) and (3)
      an inactive social-only control (SC) that served as a baseline group. Expression
      levels of BDNF and TrkB were evaluated by measuring relative optical density of
      the immunocytochemical reaction product. In cerebellar molecular layer,
      expression of BDNF correlated significantly with time spent in AC and MC over the
      first 7 days of training and remained elevated after 14 days of AC but not of MC.
      Changes in TrkB protein expression in cerebellar molecular layer mirrored those
      for BDNF during the first 7 days of training, but subsequently its expression
      subsided to the control level. In motor cortex, a significant increase in BDNF
      and TrkB protein expression was detected in the upper layers after 14 days in AC.
      Increased expression of BDNF, but not of TrkB, was observed in upper motor
      cortical layers after 14 days of MC. These data indicate that complex motor
      learning and moderate physical activity with little learning produce different
      effects on the expression pattern of BDNF and its receptor and may have
      implications for neural plasticity arising from such experiences.

PMID- 15518647
TI  - Prevention of endoplasmic reticulum stress-induced cell death by brain-derived
      neurotrophic factor in cultured cerebral cortical neurons.
AB  - Brain-derived neurotrophic factor (BDNF), one of the neurotrophic factors acting
      in the central nervous system (CNS), prevents ordinary types of neuronal cell
      death induced by various stimulants. On the other hand, an accumulation of
      unfolded proteins in the endoplasmic reticulum (ER) leads to ER stress and then
      induces ER stress-mediated cell death. The ER stress-mediated cell death is
      distinctive because the caspase-12 activity plays a crucial role in the
      progression of cell death. We previously showed that nerve growth factor (NGF)
      attenuated ER stress-mediated cell death in non-neuronal PC12 cells. Here, we
      report that BDNF suppressed the ER stress-mediated cell death in tunicamycin (Tm)
      treated cerebral cortical neurons. An analysis using a specific inhibitor of
      phosphatidylinositol 3-kinase (PI3-K), LY294002, revealed that BDNF prevented
      this cell death via the PI3-K signaling pathway. We found that the number of
      NeuN/TUNEL-double positive cells and the activity of caspase-3 suppressed by BDNF
      were increased by LY294002. We also discovered that LY294002 diminished the
      effect of BDNF on the activation of caspase-12, indicating that BDNF prevents ER
      stress-mediated cell death via a PI3-K-dependent mechanism by suppressing the
      activation of caspase-12 in cultured CNS neurons.

PMID- 15518648
TI  - Inactivation of the medial prefrontal cortex with the GABAA receptor agonist
      muscimol increases open-arm activity in the elevated plus-maze and attenuates
      shock-probe burying in rats.
AB  - This study examined the effects of infusions of a direct GABA(A) receptor
      agonist, muscimol, into the medial prefrontal cortex (MPFC), on fear behavior
      measured in the elevated plus-maze and shock-probe burying tests. Bilateral
      infusions of either a 0.175 or 4 nmol/0.5 microl dose of muscimol increased the
      percentage of entries and time spent in the open arms, and attenuated shock-probe
      burying. These findings indicate that intra-MPFC infusions of muscimol induce
      anxiolysis, and suggest that the direct stimulation of MPFC GABA(A) receptors
      attenuates fear-related behavior.

PMID- 15518649
TI  - Supranigral injection of neuregulin1-beta induces striatal dopamine overflow.
AB  - Previous studies have provided anatomical evidence that the functional neuregulin
      receptor, ErbB4, is present within the ventral midbrain where it is co-localized
      to dopamine neurons of the substantia nigra and ventral tegmental area. In this
      study, we provide evidence that neuregulin1-beta (a.k.a. heregulin1-beta), a
      neuregulin-1 gene isoform that preferentially binds to and activates the ErbB4
      receptor, evokes an almost immediate overflow of striatal dopamine when injected
      into a region just dorsal to the ipsilateral substantia nigra. These data are
      indicative that neuregulins can modulate the activity of mesostriatal
      dopaminergic neurons.

PMID- 15518650
TI  - Construction and evaluation of an average CT brain image for inter-subject
      registration.
AB  - An average CT brain image is constructed to serve as reference frame for inter
      subject registration. A set of 96 clinical CT images is used. Registration
      includes translation, rotation, and anisotropic scaling. A temporary average
      based on a subset of 32 images is constructed. This image is used as reference
      for the iterative construction of the average CT image. This approach is
      computationally efficient and results in a consistent registration of the 96
      images. Registration of new images to the average CT is more consistent than
      registration to a single CT image. The use of the average CT image is
      illustrated.

PMID- 15518651
TI  - A statistical method for the quantification of the learning index by means of
      multiple answer tests-Graduated Response Test.
AB  - In the fields of didactics and continuous professional development (CPD) plans,
      the increasing use of multiple answer tests for the evaluation of the level of
      knowledge in various kinds of subjects makes it increasingly important to have
      reliable and effective tools for data processing and for the evaluation of the
      results. The aim of the present work is to explore a new methodological approach
      based on a widely tested statistical analysis able to yield more information
      content when compared with the traditional methods. With this purpose we suggest
      a Graduated Response Test and the relative operating characteristic curve (ROC)
      for the evaluation of the results. A short description of a computerized
      procedure, written in Visual Basic Pro (v.6.0), which automatically performs the
      statistical analysis, the ROC curves plot and the calculation of a learning index
      is given as well.

PMID- 15518652
TI  - ECG characterization of paroxysmal atrial fibrillation: parameter extraction and
      automatic diagnosis algorithm.
AB  - Paroxysmal atrial fibrillation (PAF) is one of the most common heart arrhythmias.
      It is very difficult to detect unless an explicit Atrial Fibrillation episode
      occurs during the exploration. The present paper describes a number of low level
      parameters extracted from ECG traces where no Atrial Fibrillation process is
      present. The ability of this parameter set to characterize PAF patients is
      studied and discussed. Based on these parameters a modular automatic
      classification algorithm for PAF diagnosis is developed and evaluated.

PMID- 15518653
TI  - Computer simulation tool for rhinoplasty planning.
AB  - Rhinoplasty is a collection of surgical procedures performed on nose for the
      purpose of correcting functional and shape deformities. Nose is a facial feature
      which naturally draws attention during everyday contact. Any operation performed
      on nose has to blend well with the other facial features of the face. For this
      reason rhinoplasty is a type of surgery which requires artistic skills from
      surgeon as well as surgical skills. In this paper we present an artistic
      simulation tool which manipulates the shape of the nose on the bases of
      rhinoplasty procedures to be used during the surgery. Unlike other artistic
      simulation tools which can modify shape with no constraints, this tool simulates
      the effect of individual operations. Simulation tool can be valuable only if it
      predicts the outcome of the surgery with accuracy. Ultimately the outcome of the
      simulation depends largely on the experience of the surgeon. This is also the
      case with the tool presented in this study, so with experience the tool can be
      useful for predicting outcome more and more accurately. In this paper, the
      mechanical model of the nose and tools used for simulation are discussed. The
      simulation results are compared with actual rhinoplasty results to see the
      fidelity of the approach. A flowchart of the decision process and how
      rhinoplastic simulation together with the ideal nose data can be used to aid
      actual rhinoplastic surgery is given at the end.

PMID- 15518654
TI  - Development of a virtual reality environment for somatosensory and perceptual
      stimulation in the balance assessment of children.
AB  - In this study, we developed a balance assessment system in which the visual
      stimulus was generated by a virtual reality (VR) technique and somatosensation
      was obtained from a movable platform. By standing on the movable platform, the
      center of pressure (COP) was measured to express the subject's postural control
      in response to varied visual stimuli. From the COP data, a singular value
      decomposition technique was used to derive the sway area and direction,
      represented in a polar form. Our system demonstrated the feasibility of using a
      VR environment in postural control trials and provided more realistic
      somatosensory and visual inputs.

PMID- 15518655
TI  - Desensitizing and non-desensitizing subtypes of alpha-bungarotoxin-sensitive
      nicotinic acetylcholine receptors in cockroach neurons.
AB  - Two alpha-bungarotoxin-sensitive nicotinic receptor subtypes in cockroach neurons
      are identified as desensitizing (nAChD), selectively inhibitable with 100 nM
      imidacloprid, and non-desensitizing (nAChN), selectively inhibitable with 100 pM
      methyllycaconitine. Although the desensitization rate of nAChD receptors is
      highly variable, pharmacology is largely independent of desensitization rate.
      Because desensitized states tightly bind agonists, nAChD receptors are potently
      inhibited by neonicotinoids and specifically measured in radiolabeled
      imidacloprid binding assays. However, they are not usually detected in binding
      assays with radiolabeled alpha-bungarotoxin, which has a Kd for the resting state
      of 21 nM, but binds poorly to desensitized states often present in binding
      assays. In contrast, nAChN receptors are specifically measured in binding assays
      with radiolabeled alpha-bungarotoxin, which binds them with a Kd of 1.3 nM. nAChN
      receptors are activated by neonicotinoids at micromolar concentrations, and
      allosterically by spinosyn A, with an EC50 of 27 nM. Spinosyn A weakly
      antagonizes nAChD receptors -23% at 10 microM. The roles of the two nAChR
      subtypes in insecticide poisoning are discussed.

PMID- 15518656
TI  - Digestive enzymes of leaf-cutting ants, Acromyrmex subterraneus (Hymenoptera:
      Formicidae: Attini): distribution in the gut of adult workers and partial
      characterization.
AB  - Enzyme activities associated with the labial glands, midgut and rectum of adult
      Acromyrmex subterraneus were investigated in order to understand their role in
      digestion of plant and fungal material. High chitinolytic activity was detected
      in the labial glands, indicating a possible role in the degradation of fungus
      ingested by the ants. Chitinolytic activity seen in other compartments of the
      alimentary canal probably originated in the labial glands. The highest activity
      detected in the midgut was for alpha-glucosidase, which was considered to be of
      insect origin due to its association with midgut epithelium and it is probably
      involved in glucose assimilation from nutrient sources such as maltose and
      sucrose present in plant material. A large range of enzyme activities were
      detected in the rectal lumen contents, and as in the midgut the highest values
      were for alpha-glucosidase activity. The absence of activity associated with the
      epithelium, in the particulate fraction, indicates that the rectal epithelium
      does not have a secretory function. The detection of enzymes in the rectal lumen
      contents, which were not detected in the midgut lumen contents, indicates that
      the rectum acts as a reservoir, accumulating enzymes. The major digestive enzymes
      were partially characterized using hydrophobic interaction chromatography, gel
      filtration and SDS-PAGE. The pH of the adult intestinal tract and flow rate of
      dye through the tract was investigated. A gradual acidification of the intestinal
      tract was noted commencing with the crop (pH 6-8.2) and terminating with the
      rectum (pH 3-5). The flow of dye through the different compartments of the tract
      showed a rapid fill time for all the gut compartments and a short residence time
      in the crop. In all other compartments, the dye remained detectable for 10 days
      or longer.

PMID- 15518657
TI  - Wing morph-related differences in developmental pattern of accessory gland
      proteins in adult males of Pyrrhocoris apterus (L.) and their endocrine control.
AB  - The study showed that the amounts of the total proteins and 53 kDa protein in
      male accessory glands (AGs) of the firebug Pyrrhocoris apterus (L.) increased
      with age of the adult life. The 53 kDa protein, the most abundant polypeptide
      detected in the secretion of the AGs, and some other smaller peptides were
      identified as glycoproteins. Changes in the amounts of the total proteins and 53
      kDa protein in AGs were found to be wing morph-dependent and their levels were
      significantly higher in 1-10 days old brachypterous males than in macropterous
      males of the same age. Macropterous males were characterized by delayed growth of
      the AGs. Treatment of adult macropterous males with methoprene significantly
      increased the amounts of total proteins and 53 kDa protein in their AGs when
      compared to acetone-treated macropterous controls of the same age. Allatectomy of
      brachypterous males decreased the levels of the total proteins and 53 kDa protein
      in their AGs, while application of methoprene enhanced the quantity of
      allatectomy-suppressed proteins in these tissues. This is the first report of
      juvenile hormone-dependent wing morph-related differences in the synthesis of AG
      proteins and their endocrine control in wing-polymorphic insects.

PMID- 15518658
TI  - Follicular epithelial cell apoptosis of atretic follicles within developing
      ovaries of the mosquito Culex pipiens pallens.
AB  - Follicular atresia, the degeneration of developing follicles, is always incident
      to normal oogenesis in both oviparous and viviparous animals. Photo- and electron
      microscopic observation of degenerating follicles within developing ovaries taken
      from blood-fed Culex pipiens pallens mosquitoes showed gradual degradation of the
      internal structures including yolk granules in the oocyte. The epithelial cells,
      which sometimes incorporated yolk granules from the oocyte along with the
      shrinkage of the follicle, gradually lost their uniform columnar shape, while
      their integrity as a covering layer remained. In situ active caspase analysis
      detected active enzymes in these epithelial regions. In the latest stages of
      atresia where either the nurse cells or oocyte were lost, the follicle was mainly
      comprised of irregularly shaped epithelial cells, and some of these cells' nuclei
      contained condensed chromatin peripherally, one of the characteristics of
      apoptotic cells. Also terminaldeoxynucleotidyl transferase-mediated dUTP-biotin
      nick-end labeling treatment indicated that DNA fragmentation occurred in these
      follicles. It seems likely that in atretic follicles the epithelial cells survive
      to play key roles in the event, and then finally undergo their own apoptotic cell
      death so as to give the developmental site to the next follicle in the same
      ovariole.

PMID- 15518659
TI  - Patterns of chromatic information processing in the lobula of the honeybee, Apis
      mellifera L.
AB  - The honeybee, Apis mellifera L., is one of the living creatures that has its
      colour vision proven through behavioural tests. Previous studies of honeybee
      colour vision has emphasized the relationship between the spectral sensitivities
      of photoreceptors and colour discrimination behaviour. The current understanding
      of the neural mechanisms of bee colour vision is, however, rather limited. The
      present study surveyed the patterns of chromatic information processing of visual
      neurons in the lobula of the honeybee, using intracellular recording stimulated
      by three light-emitting diodes, whose emission spectra approximately match the
      spectral sensitivity peaks of the honeybee. The recorded visual neurons can be
      divided into two groups: non-colour opponent cells and colour opponent cells. The
      non-colour opponent cells comprise six types of broad-band neurons and four
      response types of narrow-band neurons. The former might detect brightness of the
      environment or function as chromatic input channels, and the latter might supply
      specific chromatic input. Amongst the colour opponent cells, the principal neural
      mechanism of colour vision, eight response types were recorded. The receptive
      fields of these neurons were not centre surround as observed in primates. Some
      recorded neurons with tonic post-stimulus responses were observed, however,
      suggesting temporal defined spectral opponency may be part of the colour-coding
      mechanisms.

PMID- 15518660
TI  - The NMDA receptor antagonist MK-801 inhibits vitellogenesis in the flesh fly
      Neobellieria bullata and in the desert locust Schistocerca gregaria.
AB  - We found that in the flesh fly Neobellieria bullata, vitellogenesis can be
      inhibited in a dose-dependent way by two injections of 60 microg MK-801/g body
      mass. In the desert locust Schistocerca gregaria, vitellogenesis can also be
      fully inhibited but only by repeated injections of 200-400 microg/g body mass. In
      this species, the inhibition can be overruled by coapplication of juvenile
      hormone. Vitellogenin bands remained visible in electropherograms of hemolymph of
      MK-801-treated female locusts, but vitellogenin did not accumulate as might be
      expected when only its uptake by the oocytes, and not its synthesis by the fat
      body, would be affected. Whether MK-801 acts by inhibiting juvenile hormone
      synthesis by the corpora allata remains to be investigated.

PMID- 15518661
TI  - Cuticular hydrocarbon dynamics in young adult Polistes dominulus (Hymenoptera:
      Vespidae) and the role of linear hydrocarbons in nestmate recognition systems.
AB  - In social insects, cuticular hydrocarbons (CHCs) play an important role in
      nestmate discrimination processes, but young individuals are usually not
      discriminated. We studied CHC changes in young workers of the social wasp
      Polistes dominulus. A quantitative estimation demonstrated that total quantities
      of CHCs increased after emergence, with branched alkanes increasing drastically
      when compared with other classes of hydrocarbons. The relative quantity of longer
      chain compounds increased with respect to shorter ones; unsaturated compounds
      decreased. These changes might reduce the capacity of the cuticle to acquire
      compounds of environmental origin. We then tested whether individuals acquire
      hydrocarbons from the environment, and whether this capability equally
      characterises newly emerged and mature wasps. We exposed wasps of two age classes
      (adults younger or older than 24 h) to four linear hydrocarbons in turn, and
      observed how nestmates reacted to their re-introduction into the natal colony.
      Exposed young wasps elicited significantly more aggressive responses than control
      sisters; but treated wasps older than 24 h were generally accepted by nestmates.
      Chemical assays showed that exposed young wasps readily absorbed hydrocarbons;
      older ones did not incorporate hydrocarbons, suggesting that the chemical
      profiles of mature wasps are less prone to chemical shifts than those of newly
      emerged wasps.

PMID- 15518662
TI  - Effect of mating stage on water balance, cuticular hydrocarbons and metabolism in
      the desert harvester ant, Pogonomyrmex barbatus.
AB  - Water-loss rates increase after mating in queens of the harvester ant
      Pogonomyrmex barbatus (Formicidae: Myrmicinae), then increase again after the
      mated queens excavate an incipient nest. We determined the mechanistic basis for
      these increased water-loss rates by examining cuticular permeability, respiratory
      water loss, metabolic rates, and cuticular hydrocarbons for queens at three
      stages in the mating sequence: unmated alate queens, newly mated dealate queens,
      and mated queens excavated from their incipient nest. Both total water loss and
      cuticular transpiration increased significantly following mating, with cuticular
      transpiration accounting for 97% of the increased water loss. In contrast,
      metabolic rate and respiratory water loss were unaffected by mating stage. The
      total quantity of cuticular hydrocarbons did not vary by mating stage. However,
      relative amounts of four of the most abundant cuticular hydrocarbons did vary by
      mating stage, as did quantities of n-alkanes and methylalkanes. The general
      pattern was that percent composition of n-alkanes decreased through the mating
      sequence, while percent composition of methylalkanes increased over the same
      sequence. We discuss three mechanisms that might cause these post-mating
      increases in cuticular permeability. Our data support the hypothesis that part of
      this increase results from soil particles abrading the cuticle during the process
      of nest excavation.

PMID- 15518663
TI  - Lectin-induced haemocyte inactivation in insects.
AB  - Most multimeric lectins are adhesion molecules, promoting attachment and
      spreading on surface glycodeterminants. In addition, some lectins have counter
      adhesion properties, detaching already spread cells which then acquire round or
      spindle-formed cell shapes. Since lectin-mediated adhesion and detachment is
      observed in haemocyte-like Drosophila cells, which have haemomucin as the major
      lectin-binding glycoprotein, the two opposite cell behaviours may be the result
      of lectin-mediated receptor rearrangements on the cell surface. To investigate
      oligomeric lectins as a possible extracellular driving force affecting cell shape
      changes, we examined lectin-mediated reactions in lepidopteran haemocytes after
      cytochalasin D-treatment and observed that while cell-spreading was dependent on
      F-actin, lectin-uptake was less dependent on F-actin. We propose a model of cell
      shape changes involving a dynamic balance between adhesion and uptake reactions.

PMID- 15518664
TI  - A morph-specific daily cycle in the rate of JH biosynthesis underlies a morph
      specific daily cycle in the hemolymph JH titer in a wing-polymorphic cricket.
AB  - A previous study documented a high amplitude, morph-specific daily cycle in the
      hemolymph JH titer in the wing-polymorphic cricket, Gryllus firmus. The JH titer
      rose and fell 10-20 fold in the flight-capable [LW(f), long-winged] morph during
      the late-photophase-early scotophase, while it was relatively constant during
      that time in the flightless (SW, short-winged) morph. In the present study we
      documented a dramatic morph-specific daily cycle in the in vitro rate of juvenile
      hormone (JH) biosynthesis that was tightly correlated with the hemolymph JH titer
      on days 5-7 of adulthood. Biosynthetic rates rose and fell 1-2 fold between the
      late photophase-early scotophase on each of days 5-6 and 6-7 of adulthood in the
      LW(f) morph, while biosynthetic rates were relatively constant during this period
      in the flightless, short-winged morph (SW), except for a slight dip in the rate
      of biosynthesis late in the photophase on these days. Similar morph-specific
      patterns of JH biosynthesis were observed whether rates were measured on corpora
      allata attached to corpora cardiaca in males or females, or on corpora allata
      alone. Hemolymph juvenile hormone esterase activity was significantly higher in
      the LW(f) vs. the SW morph during the beginning of scotophase, when the JH titer
      is decreasing rapidly in the LW(f) morph. Results indicate that the morph
      specific daily cycle in the JH titer in G. firmus is primarily regulated by a
      morph-specific daily cycle in the rate of JH biosynthesis and to a lesser degree
      by hemolymph JH esterase activity. This is the first documentation of a diurnal
      cycle in the rate of JH biosynthesis in any insect, or a daily cycle in the rate
      of JH biosynthesis that is correlated with a specific morph in a polymorphic
      species. Results have important implications for the endocrine regulation of
      dispersal polymorphism, circadian rhythms of insect hormone titers and their
      regulators, and general studies of the JH titer and its regulation in insects.

PMID- 15518665
TI  - The basis for colorless hemolymph and cocoons in the Y-gene recessive Bombyx mori
      mutants: a defect in the cellular uptake of carotenoids.
AB  - Bombyx mori is an excellent model for the study of carotenoid-binding proteins
      (CBP). In previous papers, we identified and molecularly characterized a CBP from
      the Y-gene dominant mutants. In the present study, we attempted to correlate and
      establish lipid metabolism and distribution in these mutants. When [3H]-triolein
      was fed to the mutants, typical patterns of uptake of labeled fatty acids from
      midgut to hemolymph and subsequent delivery to fat body and silk glands were
      obtained in all mutants. Further analysis of lipid and carotenoid profiles
      revealed that the yellow coloration in the hemolymph associated with lipophorin
      is not attributed to a difference in lipophorin concentrations among the mutants,
      nor to its lipid composition, but rather to its carotenoid content. Lipophorin of
      the Y+I mutant exhibited the highest concentration of total carotenoids of 55.8
      microg/mg lipophorin compared to 3.1 microg/mg in the +Y+I mutant, 1.2 microg/mg
      in the YI mutant and 0.5 microg/mg in the +YI mutant. Characteristic retention
      time in HPLC of the different classes of carotenoids of lipophorin identified the
      presence of lutein as the major chromophore (62-77%), followed by beta-carotenes
      (22-38%). Although lutein and beta-carotene content of mutants' lipophorin
      differed significantly, the ratio of lutein to beta-carotene of 3:1 was not
      different among mutants. Similarly, lipid compositions of mutant silk glands were
      not significantly different, but carotenoid contents were. The significantly high
      concentration of lutein in the Y+I mutant silk gland represented more than 160
      fold increase compared to +Y+I mutant (p<0.001). In this report, we conclude that
      lipid metabolism in the mutants is not defected and that the molecular basis for
      colorless hemolymph and cocoons is a defect in the cellular uptake of lutein
      associated with the Y-gene recessive mutants.

PMID- 15518666
TI  - Adjustment to trauma exposure: prevalence and predictors of posttraumatic stress
      disorder symptoms in mountain guides.
AB  - OBJECTIVE: The present study was designed to assess the frequency of trauma
      exposure, the prevalence rates of posttraumatic stress disorder, comorbid
      symptoms, and sense of coherence (SOC) in Swiss mountain guides. METHOD: All
      mountain guides (n=1347) were surveyed using of the Posttraumatic Stress
      Diagnostic Scale (PDS), the General Health Questionnaire (GHQ-28), and the Sense
      of Coherence Self-Rating Scale (SOC-29). RESULTS: Although Swiss mountain guides
      are exposed to many traumatic situations, the prevalence rate of PTSD is very low
      (2.7%), and their SOC total scores are high (157.9+/-18.4). Subgroups
      differentiated by the extent of traumatic stress symptoms differ significantly in
      SOC and GHQ total scores. Regression analysis showed SOC total score to be a
      significant predictor, although it only accounted for 1% of the variance in the
      number of PTSD symptoms endorsed. CONCLUSION: The low prevalence rate of PTSD is
      not in line with findings in other high-risk populations for PTSD. SOC seems to
      be a marker for psychological health rather than a protective factor against
      PTSD.

PMID- 15518667
TI  - Adjustment to trauma exposure in mountain guides.

PMID- 15518668
TI  - Depression in HIV-infected patients: allopathic, complementary, and alternative
      treatments.
AB  - OBJECTIVES: The purpose of this review article is to synthesize the current
      knowledge related to depression and HIV disease. METHODS: The research literature
      was critically evaluated for several selected therapies that are prescribed for
      HIV-infected persons to treat depression. These therapies included
      pharmacotherapy, psychotherapy, alternative, and complementary therapies.
      RESULTS: Several therapies are currently available for the treatment of
      depression in HIV disease. When prescribing treatments, clinicians should be
      aware of problems associated with diagnoses, drug-drug interactions, and the
      benefits of some of the new therapies that are now available. Treatment regimes
      should be carefully designed to meet the individual needs of the patient and will
      optimally include a combination of approaches including psychotherapy,
      pharmacotherapy, education, and/or complementary therapies. CONCLUSIONS: Although
      HIV is now a treatable disease, the prevalence of depression in the HIV
      population remains high and should be continually addressed.

PMID- 15518669
TI  - Depression and anxiety symptoms are related to increased 24-hour urinary
      norepinephrine excretion among healthy middle-aged women.
AB  - OBJECTIVE: Depression is a risk factor for morbidity and mortality in a variety
      of populations, and anxiety has also been associated with risk of mortality among
      cardiac patients. Dysfunction of the autonomic nervous system may be involved in
      this risk. The primary goal of this study was to evaluate the relationship
      between levels of self-reported symptoms of depression and anxiety and 24-hour
      urinary catecholamine excretion. METHOD: Ninety-one women aged 47-55 years were
      evaluated. Depression symptoms were assessed with the Beck Depression Inventory
      (BDI) and state anxiety was assessed with the state anxiety portion (SAI) of the
      Spielberger State-Trait Anxiety Inventory (STAI). Twenty-four hour urine
      collections were assayed for epinephrine (EPI), norepinephrine (NE) and cortisol
      (CORT). EPI, NE and CORT were indexed by body surface area to control for
      individual differences in body size. RESULTS: Higher levels of depression
      symptoms were associated with increased 24-hour NE excretion (r=.27, P=.009),
      with depressed women (n=17, BDI scores >/=10) exhibiting an approximately 25%
      higher rate of urinary NE excretion than women with BDI scores <10 (n=74),
      P=.007. Higher levels of state anxiety were also related to greater NE excretion
      (r=.28, P=.01), and CORT excretion was related to both depression (r=.23, P=.02)
      and anxiety (r=.22, P=.04). Depression and anxiety symptoms were unrelated to
      urinary EPI excretion. CONCLUSIONS: The current findings that higher levels of
      depression and anxiety symptoms are related to increased 24-hour urinary NE and
      CORT excretion among women suggests that depression and anxiety may be associated
      with increased sympathetic nervous system (SNS) activity, and are consistent with
      the possibility that SNS activity may play a role in the increased mortality
      associated with depression in community-dwelling older adults.

PMID- 15518670
TI  - Age at menarche and depression at the age of 31 years: findings from the Northern
      Finland 1966 Birth Cohort Study.
AB  - OBJECTIVE: Early age at menarche has been found to be associated with higher
      oestrogen levels among girls around the onset of puberty and in early adulthood.
      The role of oestrogen in depression is not clear, although it affects
      serotonergic functions in the central nervous system (CNS). We wanted to test the
      hypothesis that age at menarche is associated with depression in young adulthood.
      METHODS: The material consisted of 3952 women born in 1966 in Northern Finland.
      Depression was defined by the Hopkins Symptom Checklist-25 (HSCL-25), the use of
      antidepressants and by self-reported lifetime depression diagnosed by physician.
      Menarcheal age was divided as 9-11, 12-15 and 16 years or over. RESULTS: The
      prevalence of depression was 1.8-fold in current depression, 2.8-fold in the use
      of antidepressants and 2.1-fold in self-reported physician-diagnosed depression
      in women with menarche at the age of 16 years or later. After adjusting for
      confounders, the significant positive association between current depression and
      late menarche remained, but the use of antidepressants and depression diagnosed
      by physician had not statistically significant association with the age of
      menarche. CONCLUSION: A possible explanation for the result may be oestrogen as a
      protective factor against depression.

PMID- 15518671
TI  - Autobiographical memories in patients treated for breast cancer.
AB  - OBJECTIVE: Previous research has shown that several clinical groups have
      difficulties with generating specific autobiographical memories. The aim of this
      study was to investigate autobiographical memory function in women who had been
      treated for breast cancer and to compare those patients who had undergone
      mastectomy only with those who had undergone breast reconstruction surgery after
      mastectomy. METHOD: A sample of 26 women treated for breast cancer were tested
      via telephone using the Autobiographical Memory Test (AMT). RESULTS: Breast
      cancer patients had difficulty retrieving specific autobiographical memories
      compared to a group of age-matched controls without any history of breast cancer.
      There were essentially no differences between the two patient groups. CONCLUSION:
      Since breast cancer patients are vulnerable to emotional distress,
      autobiographical memory deficits should be investigated further.

PMID- 15518672
TI  - Causal illness attributions in somatoform disorders: associations with
      comorbidity and illness behavior.
AB  - OBJECTIVE: To compare causal illness beliefs between patients with unexplained
      physical symptoms and different comorbid disorders and to assess the association
      of causal illness beliefs with illness behavior. METHODS: We examined a sample of
      233 patients attending treatment in primary care. Inclusion criteria were
      "unexplained physical symptoms." All patients were investigated using structured
      interviews and self-rating scales [Screening for Somatoform Symptoms (SOMS), Beck
      Depression Inventory (BDI), Beck Anxiety Inventory, and a 12-item instrument to
      assess causal attributions]. By means of factor analysis, the following illness
      attributions were considered: vulnerability to infection and environmental
      factors, psychological factors, organic causes including genetic and aging
      factors, and distress (including exhaustion and time pressure). RESULTS: Most
      patients reported multiple illness attributions. The more somatoform symptoms
      patients had, the more explanations in general they considered. Especially for
      vulnerability and organic illness beliefs, patients with somatoform symptoms had
      increased scores. Comorbidity with depression and with anxiety disorders was
      associated with more psychological attributions. Even when the influence of
      somatization, depression, and anxiety is controlled for, illness beliefs still
      showed associations with illness behavior. Organic causal beliefs and
      vulnerability attributions were associated with a need for medical diagnostic
      examinations, increased expression of symptoms, increased illness consequences,
      and bodily scanning. CONCLUSIONS: Multiple causal attributions can coexist
      demonstrating different associations with comorbid depression and illness
      behavior.

PMID- 15518673
TI  - Perceived stigma in functional somatic syndromes and comparable medical
      conditions.
AB  - OBJECTIVE: To determine if patients with functional somatic syndromes (FSS)
      perceive greater levels of stigma than patients with comparable medical
      conditions that have a clear medical pathology. METHODS: Patients with chronic
      fatigue syndrome (CFS), fibromyalgia (FM), or irritable bowel syndrome (IBS) were
      compared to multiple sclerosis (MS), rheumatoid arthritis (RA), and inflammatory
      bowel disease (IBS), respectively. RESULTS: There were greater levels of
      perceived stigma in the combined group of FSS compared to the medical control
      group. When each FSS was compared to its matched control group, only CFS had a
      higher level of perceived stigma. These results remained when controlling for
      other variables relevant to stigma. CONCLUSIONS: The higher level of perceived
      stigma in CFS may be due to the ambiguity of its status as a medical condition.
      The absence of this effect in FM and IBS is consistent with a greater level of
      acceptance of these disorders as medical illnesses.

PMID- 15518674
TI  - Multiple medically unexplained physical symptoms and health care utilization:
      outcome of psychological intervention and patient-related predictors of change.
AB  - OBJECTIVES: To test the effect of psychological intervention on multiple
      medically unexplained physical symptoms, psychological symptoms, and health care
      utilization in addition to medical care as usual. To identify patient-related
      predictors of change in symptoms and care utilization. METHODS: In a randomized
      controlled trial, subjects were assigned to one of two conditions: psychological
      intervention by a qualified therapist plus care as usual by a general
      practitioner (GP) or care as usual only. Participants (N=98) were administered a
      standardized interview and several outcome measures at intake and after 6 months
      and 12 months after intake. GPs rated medically unexplained and explained
      symptoms and consultations over a period of 1 1/2 years. RESULTS: ANOVAs for
      repeated measures showed that self-reported and GP-registered unexplained
      physical symptoms decreased from pretest to posttest to follow-up. Psychological
      symptoms and consultations decreased from pretest to posttest. GP-registered
      explained symptoms did not decrease. However, intervention and control groups did
      not differ in symptom reduction. Path analysis revealed two paths to a decrease
      in self-reported unexplained physical symptoms: from more negative affectivity
      via more psychological attribution and more pretreatment anxiety, and from more
      somatic attribution via more psychological attribution and more pretreatment
      anxiety. CONCLUSION: Intervention and control groups did not differ in symptom
      reduction. Reduction of self-reported medically unexplained symptoms was well
      predicted by patient-related symptom perception variables, whereas the prediction
      of change in registered symptoms and consultations requires a different model.

PMID- 15518676
TI  - The relation between pathological worrying and fatigue in a working population.
AB  - OBJECTIVE: This study aimed to explore cross-sectional and longitudinal
      associations between pathological worry and fatigue in a working population.
      METHODS: In employees with very low or very high fatigue levels, psychometrics of
      the Penn State Worry Questionnaire (PSWQ; measuring pathological worry) and the
      Checklist Individual Strength (CIS; measuring fatigue) were examined and their
      cross-sectional and longitudinal associations were explored. RESULTS:
      Pathological worry and fatigue can be measured as different constructs. However,
      pathological worry and fatigue were also associated on a cross-sectional level.
      Pathological worry predicted fatigue level 10 months later, but this association
      disappeared after adjustment for the cross-sectional association between
      pathological worry and fatigue. CONCLUSION: Although they can be measured as
      different constructs, pathological worry and fatigue seem to be associated. When
      studying longitudinal relations between pathological worry and fatigue, their
      cross-sectional association should be taken into account. Pathological worry
      might not be a risk factor for fatigue per se, but might act more like a
      mediating factor.

PMID- 15518675
TI  - The effect of brief exercise cessation on pain, fatigue, and mood symptom
      development in healthy, fit individuals.
AB  - OBJECTIVE: Abnormalities of the biological stress response (hypothalamic
      pituitary-adrenal axis and the autonomic nervous system) have been identified in
      both fibromyalgia (FM) and chronic fatigue syndrome (CFS). Although these changes
      have been considered to be partly responsible for symptom expression, we examine
      an alternative hypothesis that these HPA and autonomic changes can be found in
      subsets of healthy individuals in the general population who may be at risk of
      developing these conditions. Exposure to "stressors" (e.g., infections, trauma,
      etc.) may lead to symptom expression (pain, fatigue, and other somatic symptoms)
      in part by precipitating lifestyle changes. In particular, we focus on the effect
      of deprivation of routine aerobic exercise on the development of somatic
      symptoms. METHODS: Eighteen regularly exercising (>/=4 h/week) asymptomatic,
      healthy adults refrained from physical activity for 1 week. We predicted that a
      subset of these individuals would develop symptoms of FM/CFS with exercise
      deprivation, and this manuscript focuses on the baseline HPA axis, immune, and
      autonomic function measures that may predict the development of symptoms.
      RESULTS: Eight of the subjects reported a 10% increase in one or more symptoms
      (pain, fatigue, mood) after 1 week of exercise deprivation. These symptomatic
      subjects had lower HPA axis (baseline cortisol prior to VO2max testing), immune
      (NK cell responsiveness to venipuncture), and autonomic function (measured by
      heart rate variability) at baseline (prior to cessation of exercise) when
      compared to the subjects who did not develop symptoms. CONCLUSIONS: A subset of
      subjects developed symptoms of pain, fatigue, or mood changes after exercise
      deprivation. This cohort was different from the individuals who did not develop
      symptoms in baseline measures of HPA axis, immune, and autonomic function. We
      speculate that a subset of healthy individuals who have hypoactive function of
      the biological stress response systems unknowingly exercise regularly to augment
      the function of these systems and thus suppress symptoms. These individuals may
      be at risk for developing chronic multisymptom illnesses (CMIs) (e.g., FM or CFS
      among others) when a "stressor" leads to lifestyle changes that disrupt regular
      exercise.

PMID- 15518678
TI  - Asian transplant registry.

PMID- 15518679
TI  - Immunosuppression use in renal transplantation from Asian transplant centers: a
      preliminary report from the Asian Transplant Registry.
AB  - Since the first renal transplant (RTx) in 1956 in Asia in Japan, over 100,000 RTx
      have been performed in over 300 centers across the region. A survey was conducted
      to evaluate immunosuppression (IS) use among Asian RTx. Briefly, directors of RTx
      centers were surveyed regarding IS use for RTx performed at their centers in 2001
      for (1) induction therapy, (2) maintenance IS therapy at hospital discharge, (3)
      antirejection treatment (REJ) to 1 year post-RTx, and (4) maintenance IS therapy
      to 1 year post-RTx. Categories and types of IS included in the survey were
      polyclonal antilymphocyte antibodies (PAB), OKT3, IL2 receptor antibodies
      (IL2RAb), corticosteroids (CS), cyclosporine (CyA), tacrolimus (Tac),
      azathioprine (Aza), mycophenolate mofetil (MMF), Mizoribine (Miz), Sirolimus
      (Sir), and other agents. Though only 17 RTx centers in Asia responded to the
      survey, a wide variation in IS use was demonstrated. In the 334 living and 85
      cadavericRTx among whom actual usage was reported, induction therapy was used in
      only 18.4% of Asian RTx (14.1%, IL2RAb; 4.3%, PAB), in contrast to the 59.3%
      reported as using induction IS among RTx from the UNOS database in the same year.
      For maintenance therapy at hospital discharge, 87.1% of Asian RTx received CyA
      based IS while only 12.4% received Tac-based therapy. This is in contrast to the
      55.3% use of Tac for new RTx in the United States. Generic CyA has widespread use
      in Asia with over 29.9% on CyA using generic versus the Neoral formulation.
      Azathioprine is still the predominant antimetabolite in use in Asian RTx, with
      MMF being used in only 33.6% of patients, in contrast to its 77% usage in the
      United States. Usage of Tac and MMF for maintenance therapy was significantly
      higher among cadavericRTx (P < .005). Corticosteroids were used in 51.1% of REJ
      episodes while PAB or OKT3 were used in 31.9% and 17% of REJ episodes,
      respectively. As these results may be skewed due to participation of few centers
      in the survey, greater participation will ensure more accurate evaluation of
      immunosuppression use in Asia for de novo RTx.

PMID- 15518680
TI  - Improving cadaveric organ donation rates in kidney and liver transplantation in
      Asia.
AB  - In the year 2001, cadaveric kidney and liver transplant rates (CadTx) in
      countries with well-established transplant programs such as the United States and
      Spain ranged from 51 to 61.9 and 18.7 to 31.3 per million population (pmp),
      respectively. However, overall kidney and liver transplant rates in Asia are
      significantly lower at 4.3 and 0.3 pmp, respectively. Improving CadTx rates to
      meet the needs of organ failure patients poses several unique challenges in Asia.
      Across Asia, there is a wide disparity in prehospital emergency services and
      intensive care facilities that allow victims of cerebrovascular accident or
      trauma to be sent to hospitals for optimal management. Identification of the
      brain-dead victim in an intensive care setting, donor referral to an organ
      procurement coordinator/network, making the request for organ donation, and
      obtaining consent for organ donation from the family are other critical issues
      that impact on successful cadaveric donation. While affirmative legislation
      regarding organ donation is existent in most Asian countries, religious, ethnic,
      and cultural influences on concepts of death and the sanctity of the human body
      remain major barriers to obtaining consent for cadaveric donation. Although there
      are no overt objections to CadTx among the major religions of Asia, perceptions
      to the contrary largely limit consent for organ donation from potential donor
      families. Development of transportation and communication networks, public and
      donor hospital education programs, legislative initiatives such as presumed
      consent, and establishment of effective organ procurement practices are all key
      initiatives that will improve CadTx rates. Broadening donor criteria as with the
      use of expanded criteria donors, including non-heart-beating and older donors,
      may further improve cadaveric donation rates by as much as 20%. Finally, ethical
      transplant practices that prohibit trade in organs will promote an environment
      conducive to cadaveric donation. Together with efforts to increase living donor
      TX transplant rates, it is hoped that these measures will increase the supply of
      organs so as to meet the needs of organ failure patients in Asia.

PMID- 15518681
TI  - Paid organ procurement: pragmatic and ethical viewpoints.
AB  - None of the familiar arguments against paid organ procurement really works. Most
      arguments spring from revulsion that arises from the abuses of the practice
      rather than the act itself. This has not stopped official condemnation. However,
      the evidence we have at present is that such condemnation, aimed at correcting a
      perceived moral wrong rather than at abuses of a practice (the correction of
      which might actually bring some moral good), has utterly failed, and many more
      countries including the United States now harbor paid organ procurement. We can
      try to develop and articulate a truly compelling moral argument against paid
      organ procurement or we can try to minimize the harm that comes out of this
      practice. Since it is unlikely that all countries will agree on a standardized
      approach in such a muddled field, the best way may be to let every country decide
      on what is best for itself. Some may want to ban the practice using legislation.
      Others may want to try regulating the practice, knowing full well that they
      cannot stop it and that turning a blind eye to the practice, or simply condemning
      it, does no good whatsoever and actually increases the harm because everything is
      done underground, with middlemen and mafia-like organizations making a lot of
      money out of a lot of misery. Some countries may choose to find other, more
      innovative solutions. We call attention to an important resolution dealing with
      this subject at the December 2002 ethics and transplantation congress in Munich.

PMID- 15518682
TI  - Increasing organ donation rates from Muslim donors: lessons from a successful
      model.
AB  - As the great majority of the population in Saudi Arabia is Muslim, the Islamic
      views about organ donation and transplantation have been the focus of interest to
      the transplant community in this and other Muslim countries. The first resolution
      of the Islamic council in Saudi Arabia (Senior Ulama Commission) about organ
      donation and transplantation was issued in 1982. It permitted tissue and organ
      transplantation from both living and cadaveric donors. This resolution marked a
      new era in organ transplantation in Saudi Arabia, leading to the formation of the
      Saudi Center of organ transplantation (SCOT), which organizes the process of
      organ donation and transplantation in Saudi Arabia. There were major strategies
      to reach the goals of the organ procurement centers adopted by SCOT: improving
      the awareness of the medical community to the importance of organ donation and
      transplantation, improving the awareness of the public at large to the importance
      of organ donation and transplantation, and developing an efficient coordinated
      system with both the donating hospitals and the transplant centers. Various
      organs had been transplanted in Saudi Arabia through the end of 2002: 3759 kidney
      transplants (1267 cadaver, 2492 living); 279 liver transplants(225 cadaver, 54
      living); 92 heart transplants; 421 cornea transplants; 8 lungs; and 5 combined
      kidneys and pancreas. In addition, there have been many tissue donations of bone
      marrow, heart valves (264 hearts), skin, and bone. Despite the success of the
      Saudi program, there have been public and medical obstacles that have obviated
      the full benefit of cadaver donors. We suggest increasing the awareness of the
      medical community and the public at large to the importance of organ donation and
      transplantation.

PMID- 15518683
TI  - The efficiency of utilization of potential donors for organ transplantation in
      Saudi Arabia: a pilot study.
AB  - Organ shortage has been the main obstacle in the progress of organ
      transplantation in Saudi Arabia. The aim of this pilot study was to determine the
      percentage of potential donors among all deaths in Riyadh hospital intensive care
      units (ICUs). Mortality data were collected by a medical professional in each ICU
      and analyzed on weekly basis for 1 year (June 2001 through May 2002): The final
      analysis at the end of the year showed the number of brain death cases in all
      hospitals to be 114 out of 542 deaths. Fifty-four percent occurred in one
      hospital. Thirty-eight cases were reported to the Saudi Center for Organ
      Transplantation (33%). Documentation was completed in only 23 cases (60%). Only
      four cases became actual donors. In conclusion, there is underreporting of brain
      death cases. Dealing with the reported cases is inefficient since only four cases
      became actual donors out of 38. Improving the efficiency of ICUs in dealing with
      brain death cases (reporting, documentation, maintenance and consent) will
      require solving several problems at the medical, administrative, religious, and
      mass media levels.

PMID- 15518684
TI  - Knowledge and attitude of intensivists toward organ donation in Riyadh, Saudi
      Arabia.
AB  - Organ transplantation has been widely accepted as a solution for end-stage organ
      failure. The limitation has been organ shortage. The intensivist plays a major
      role in the different stages of the donation process. This study investigated the
      knowledge and attitude toward organ donation and transplantation amongst
      intensivists in the major hospitals of Riyadh. The study was conducted in June
      2002. Twenty-two intensivists in the intensive care units (ICUs)of 4 hospitals in
      Riyadh participated in the study. A questionnaire was distributed concerning
      knowledge and attitude on donation and transplantation. The information was
      tabulated and analyzed. Only 50% appreciated the high success rate of modern
      organ transplantation. One fourth did not know of the role of the Saudi Center
      for Organ Transplantation (SCOT). Most of the intensivists knew the Islamic view
      on transplantation. Many would be willing to allow donation from a deceased
      relative. However, only 13% carry donation cards. Most participants believed that
      the organ shortage was mainly due to family refusal to donate. Intensivists need
      to have better insight into the obstacles to donation that can be solved at the
      level of the hospital and the ICUs. Moreover, the communication gap between ICUs
      and SCOT needs to be bridged to optimize the use of all potential donors.

PMID- 15518685
TI  - Non-heart-beating donation: ten evidence-based ethical recommendations.
AB  - The renewed interest in non-heart-beating donation (NHBD) in the past decade has
      resulted in renewed examination of the concept and meaning of death; of the
      nature of consent; of the propriety of interventions for the benefit of the
      recipient and not the donor; of potential conflicts of interest; and of defining
      futility. There is recognition of the need to maintain public trust. Recent
      experience indicates that NHBD could make a significant contribution to total
      renal transplant numbers. While there is graft dysfunction in the short term, the
      long-term results are comparable to those of transplants from heart-beating
      kidney donors, and in one series, even to living donors. The University of
      Zurich's experience indicates that waiting 10 minutes after asystole and not
      using in situ cooling do not adversely affect long-term outcomes. NHBD under
      ideal conditions could be extended to other organs such as the liver and
      pancreas. Ethical concerns are not insurmountable and can be minimized if cooling
      procedures and the use of drugs, such as heparin and phentolamine, is minimized,
      and if a period of 10 minutes is allowed to elapse after asystole before death is
      declared. We make a series of evidence-based recommendations for protocol
      development.

PMID- 15518686
TI  - Kidney transplantation from non-heart-beating donors: analysis of organ
      procurement and outcome.
AB  - INTRODUCTION: Most donors in Japan have been non-heart-beating donors (NHBD), so
      called "marginal donors." In Western countries kidney transplants from NHBD have
      also been increasing. We analyzed 120 kidneys harvested from NHBD with regard to
      organ procurement, renal function, graft survival, and the donor factors that
      affected graft survival. METHODS: Donors were moved into the operating room after
      cardiac arrest. A double-balloon catheter was inserted into the abdominal aorta
      via laparotomy. In situ cooling by Euro-Collins solution was started at 500
      mL/min. We did not performed cannulation into the femoral artery or vein prior to
      cardiac arrest. RESULTS: Warm ischemia time (WIT) was 18.6 minutes. Among 108
      kidneys (90%) used for transplantation, 102 kidneys functioned. There were no
      cases of bilateral nonfunctioning kidneys. The delayed graft function (DGF) rate
      was 86%; however, the death-censored graft survival was 80.0% at 5 years and
      62.9% at 10 years. Kidneys implanted after more than 24 hours of total ischemia
      time required a significantly longer period of hemodialysis. Donor risk factors
      that affected graft survival included WIT >/= 20 minutes, donor age >/= 50 years,
      and serum creatinine level at admission > 1.0 mg/dL. CONCLUSIONS: Organ
      procurement without cannulation prior to cardiac arrest entailed a long WIT and a
      high DGF rate. However, the graft survival was good. It has been necessary to use
      grafts from NHBD despite the inherent risk factors. It is important to reduce
      kidney damage both at the organ procurement and during the posttransplant
      management.

PMID- 15518687
TI  - Non-heart-beating donation: current state of the art.
AB  - The use of non-heart-beating donors (NHBD) helps us to deal with the problem of
      the organ shortage. In addition to difficulties with legal and ethical
      acceptability, there are concerns regarding medical safety, which prevent the
      widespread use of these donors. To make optimum use of this potential organ
      supply, the ischemic injury that occurs after a period of warm ischemia needs to
      be reversed. To minimize the warm ischemia time, once the subject is declared
      dead, most centers commence in situ cold perfusion via a femoral access or a
      rapid aortic cannulation. This usually occurs within minutes of arriving at the
      emergency department, before the next of kin have been notified of the patient's
      death. The European experience of kidney transplantation from NHBD shows
      promising results. The long-term outcomes are similar to HBD kidneys
      notwithstanding a higher rate of delayed graft function, which seems not to
      affect the long-term survival of these kidneys. In summary, NHBD may have an
      important impact on the large discrepancy that exists between the organ supply
      and the demand. Current data suggest that the results may be further improved by
      better patient selection and retrieval team organization.

PMID- 15518688
TI  - Improving kidney and live donation rates in Asia: living donation.
AB  - Organ transplantation started with organs donated by living subjects. Increasing
      demands brought cadaveric organ donation. The brain-death law, mandatory for this
      procedure, is prevalent in all countries involved in organ transplantation except
      Pakistan. Spain is the leading country in cadaveric organ donation (32.5 pmp).
      Despite the sources of living and cadaveric organs, both heart-beating and non
      heart-beating, the gap between the demand and supply has widened. An example is
      the United States, where the numbers of patients on the waiting list for kidney
      transplantation have risen from 30,000 in 1988 to more than 116,000 in 2001. This
      has caused a resurgence in living donors all over the world. These can be
      related, unrelated, spousal, marginal, or ABO-incompatible donors. Family
      apprehensions, medical care costs, and nonexistent social security can be
      barriers to this form of organ donation. Unrelated organ donation can open the
      doors to commercialism. To make this process more successful, transplantation
      should be made reachable by all sectors of the population. This is possible when
      transplantation is taken to the public sector institutions and financed jointly
      by the government and community. To increase living organ donation especially in
      Asian countries, which face barriers of low literacy rates, ignorance, and
      cultural and religious beliefs, more efforts are needed. Public awareness and
      education play an important role. Appreciation and supporting the donors is
      necessary and justified. It is a noble act and should be recognized by offering
      job security, health insurance, and free education for the donor's children.

PMID- 15518689
TI  - Attitudes of black South Africans to living related kidney transplantation.
AB  - Between September 1992 and April 2003, 96 patients in chronic renal failure had
      134 potential related living donors. The aim of this study was to determine the
      factors that influence living related kidney transplantation among black South
      Africans. METHODS: Potential recipients and donors were screened for suitability
      to donate or receive kidneys. The relationship of the donor to the recipient was
      documented. RESULTS: Ninety-six potential recipients of median age 32 years
      (range, 7 to 53) and a female to male ratio of 1:1.6 had potential related
      donation from 47 sisters, 33 brothers, 27 mothers, 8 fathers, and 11 children.
      Eight potential donors were from cousins, spouses, stepbrothers, and friends.
      One, two, or three potential donors per recipient were counted among 54, 19, and
      10 recipients, respectively. Contraindications to transplantation in 45 potential
      donors were ABO incompatibility (n = 19); hypertension (n = 11); HIV positivity
      (n = 10); and one each for nephrotic syndrome, gastric cancer, Hepatitis B,
      withdrawal, and a single functioning kidney. Thirty-five patients were
      transplanted from relatives. Although HLA-A, B, and DR antigens were studied in
      transplanted patients using both serologic and polymerase chain reaction-sequence
      specific oligonucleotide methods, HLA matching was not used for donor selection.
      Only two living related pairs were HLA identical. Actual 1-year graft survival
      after transplantation was 95%. In conclusion, the concept of related living
      donation is acceptable among black South Africans and the number of donors per
      recipient suggests that HLA matching can be improved.

PMID- 15518690
TI  - Hand-assisted laparoscopic live donor nephrectomy: report of 100 cases.
AB  - INTRODUCTION: Laparoscopic live donor nephrectomy is not yet widespread in Japan.
      After our first hand-assisted laparoscopic live donor nephrectomy (HALapNx) in
      2001, we report our 100 cases and examine the possibility of making this
      technique widely available in Japan. METHODS: HALapNx was performed in 100 cases
      (44 males and 56 females) from February 2001 through July 2003. The operative
      procedure for HALapNx was briefly described here. First, 2 12-mm ports were
      placed in the midaxillary line at the superior and inferior level of the
      umbilicus. Next, a 5-cm incision was made in the midline periumbilicus and the
      hand port system was fitted through the abdominal incision. After 10 mm Hg
      pneumoperitoneum, HALapNx begins with mobilization of the left colon. RESULTS:
      HALapNx was completed successfully in all cases and no patients required
      conversion to laparotomy. The estimated blood loss was 33.5 +/- 40.3 g and no
      patient required blood transfusion. The mean operative time was 168.8 +/- 47.6
      minutes, and there was no major complication in a donor. CONCLUSIONS: HALapNx is
      technically feasible and may offer several advantages over open donor nephrectomy
      in terms of less blood loss, less postoperative pain, and minimal cosmetic
      disfigurement. In Japan, laparoscopic donor nephrectomy is not yet widespread,
      possibly due to the need for surgical laparoscopic skills. We believe that the
      best way to make laparoscopic donor naphrectomy widely available is through hand
      assisted laparoscopic surgery.

PMID- 15518691
TI  - Initial experience with laparoscopic donor nephrectomies.
AB  - BACKGROUND: Laparoscopic donor nephrectomy (LDN) is being adopted rapidly by
      transplant centres around the world as it offers less postoperative pain, quicker
      convalescence, and better cosmetic result when compared with the open approach.
      There may, however, be a steep learning curve with this technique. METHOD: A
      retrospective review was performed to evaluate the donor morbidity and graft
      outcome of 21 consecutive LDN performed at one centre between May 2002 and August
      2003. RESULTS: Eighteen LDN were performed on the left and three on the right
      side. All left and one right LDN were done transperitoneally while the remaining
      two right side kidneys were removed by a retroperitoneal approach. The mean (+/
      SD) operating time and warm ischemic time were, respectively, 236 minutes (+/-
      46) and 4 minutes (+/- 1). The mean time for resuming oral intake was 23 hours
      (SD +/- 22.7). The median length of hospital stay was 5 days (range 3 to 18). One
      patient was reoperated for bleeding and required four units of packed cell
      transfusion. One recipient displayed delayed graft function requiring dialysis
      for 14 days. There were no graft losses. The mean creatinine of the recipients at
      the time of discharge was 1.15 mg/dL (+/- 0.21). CONCLUSIONS: There is
      undoubtedly a learning curve with LDN. Nevertheless, with prior skills in similar
      procedures such as laparoscopic radical nephrectomies, it is feasible to diminish
      the learning curve and morbidity of LDN to yield results consistent with those in
      the published literature.

PMID- 15518692
TI  - Hand-assisted transperitoneal laparoscopic living donor nephrectomy.
AB  - OBJECTIVE: We introduced and evaluated the advantages and disadvantages of the
      hand-assisted transperitoneal laparoscopic technique for living donor
      nephrectomy. MATERIALS AND METHODS: In December 2001, we started using the
      technique of hand-assisted transperitoneal laparoscopic living donor nephrectomy
      (HLDN) in 10 cases. The procedure utilizes a hand-assisted device to increase
      safety and control of the laparoscopic technique. RESULTS: Only left nephrectomy
      was performed. The mean total operating and the warm ischemia times were 130
      minutes and 3.0 minutes, respectively. Average lengths of renal artery and vein
      were 1.95 cm and 2.8 cm, respectively. There were no intraoperative or
      postoperative complications. CONCLUSIONS: HLDN is an easier procedure than the
      traditional laparoscopic living donor nephrectomy and can greatly mitigate the
      learning curve. HLDN has shortened warm ischemia time and operating time. It is
      also good for trocar placement, prevention of torsion of the kidney, control of
      potential bleeding at the final stage of vascular stapling, and kidney removal.
      Therefore, HLDN is a promising method for living donor nephrectomy.

PMID- 15518693
TI  - Terminal hand-assist for laparoscopic donor nephrectomy.
AB  - BACKGROUND: Laparoscopic donor nephrectomy (LDN) has become widely popular in
      developed countries but not so in developing countries. One explanation for this
      maybe the difficulty in getting access devices due to the prohibitive cost. We
      report our method of terminal hand-assisted LDN in which successful donor
      nephrectomy is feasible without expensive access devices. METHOD: The patient is
      placed in the corresponding classic renal surgery position. Three ports are
      placed for left-sided and four for right-sided LDN. After complete mobilization
      of the kidney laparoscopically, the assistant's right hand is introduced for left
      sided LDN through a 7-cm left lower quadrant transverse muscle-splitting
      incision. For right-sided LDN, the surgeon's right hand is inserted through a
      corresponding ipsilateral incision (for right-handed surgeons). A simple method
      to prevent the leakage of pneumoperitoneum is described. The hand inside the
      abdomen aids in the final steps and completes the extraction of the kidney
      swiftly. Manual mopping, lavage, and hemostasis are also possible. RESULTS: Five
      cases of LDN at our centre were done in this fashion, four on the left side and
      one on the right. The mean kidney retrieval time after clamping the renal artery
      was 3:18 +/- 0:46 minutes (range 2:30 to 4:30). Postoperative stay was 4 to 5
      days. Recipient serum creatinine normalized within 3 to 4 days. CONCLUSIONS:
      Short duration terminal hand-assist for LDN without any special access device is
      possible without the fear of excessive gas leakage. It is helpful to reduce
      prolonged warm ischemia and to relieve the surgeon's apprehension, at least in
      the initial learning phase of LDN.

PMID- 15518694
TI  - Right-sided laparaoscopic donor nephrectomy is feasible: experience with three
      cases.
AB  - BACKGROUND: Laparoscopic donor nephrectomy (LDN) is more difficult on the right
      than the left and is typically not recommended for the right kidney. MATERIALS
      AND METHODS: Between November 2002 and May 2003, three patients underwent right
      sided donor nephrectomy: one transperitoneally and two retroperitoneoscopically.
      All procedures were performed in the right kidney position. Three ports were
      placed for retroperitoneoscopic approach and four for transperitoneal, including
      one to retract the liver. Renal arteries were clipped thrice and divided, and
      renal veins divided using an endo-GIA30 stapler. Kidneys were retrieved in all
      cases by extending the lower port incision by 7 to 8 cm. The records of donors
      and recipients, including early graft outcomes were reviewed. RESULTS: Kidney
      retrieval time and total warm ischemic time were 3:30 minutes and 5 minutes,
      respectively, for transperitoneal LDN and 3:40 to 4:10 minutes and 5 to 7
      minutes, respectively, for retroperitoneal LDN. The operating times were 176,
      224, and 160 minutes, respectively. The first donor (transperitoneal) was
      discharged on the fourth postoperative day, and the other two (retroperitoneal)
      on the third day. The serum creatinine of all recipients normalized within 72
      hours, with normal isotope renal scans on the fifth postoperative day.
      CONCLUSIONS: Right-sided LDN is feasible and safe without adversely affecting
      graft quality. The retroperitoneal approach is technically easier, gives a longer
      length of renal artery, and has a quicker convalescence.

PMID- 15518695
TI  - Laparoscopic donor nephrectomy: new combination of hand-assisted and standard
      approaches.
AB  - BACKGROUND: Although laparoscopic live donor nephrectomy (LLDN) was conceived to
      decrease morbidity and reduce donor disincentives, it requires considerable
      experience. We present a new combination of hand-assisted and standard
      laparoscopic approaches to live donor nephrectomy. METHODS: Between March 2002
      and February 2003, ten LLDNs were performed with the new procedures. Using the
      new methodology the surgeon can withdraw his hand and insert a trocar through the
      hand-assisted device whenever he desires. Although the hand-assisted procedure
      was performed in most patients, we attempted to dissect the renal hilum without
      hand assistance in the final patient, successfully procuring the kidney. RESULTS:
      Mean operation time was 245 minutes and warm ischemic time was 179 seconds. No
      vascular, renal parenchymal, or ureteral injuries occurred. The patient with
      multiple left renal arteries had a longer warm ischemic time and delayed graft
      function. Mean predonation creatinine was 0.97 mg/dL, it increased to 1.44 and
      1.15 mg/dL at 7 days and 3 months postdonation, respectively. One patient had
      chylous ascites and another had a transient left brachial plexus paralysis.
      CONCLUSIONS: Both pure laparoscopic and hand-assisted LLDN have advantages and
      disadvantages. In our modification, the free conversion from hand-assisted to a
      purely laparoscopic approach allows the surgeon to practice two procedures
      simultaneously. With this combination, 90% of the LLDN were accomplished, with
      pure laparoscopy in the last case.

PMID- 15518696
TI  - Laparoscopic live donor nephrectomy in a patient with duplex inferior vena cava.
AB  - BACKGROUND: Modern imaging, such as CT and MRI, improves the preoperative
      assessment for variants of renal vasculature. We present a kidney donor with a
      duplex inferior vena cava. In conjunction with CT and hand-assisted laparoscopic
      surgery, live donor nephrectomy was performed successfully. METHODS: A 35-year
      old woman wished to donate a kidney to her son. Preoperative CT showed normal
      functional kidneys without uretal duplication. A duplex inferior vena cava was
      noted below the level of the left renal vein. A hand-assisted transperitoneal
      laparoscopic left nephrectomy was performed. Blood loss was minimal and the warm
      ischemia time was 3 minutes. Renal transplantation was performed with good
      initial perfusion and urine output. RESULTS: The donor was discharged in good
      condition at 3 days postoperatively. Both donor and recipient are alive with good
      renal function and without late surgical complications at 9 months. CONCLUSIONS:
      Live donor nephrectomy is unique as it involves two different patients. Benefits
      from laparoscopic operation include less pain, shorter hospital stay, earlier
      resumption of normal food intake, and earlier return to full activity. Graft
      function was not deleteriously affected and the survival of graft and recipient
      was not affected. Vascular anomalies, although uncommon, had a significant
      influence on live renal transplantation. Our patient represents a case of a rare
      venous anomaly, which has an an incidence rate of 0.5% to 3%. Helical CT with
      reconstruction of vascular anatomy helped in evaluating donor vasculature. In
      conjunction with modern imaging techniques and laparoscopic operation, live donor
      nephrectomy can be performed safely, even in patients with vascular anomalies.

PMID- 15518697
TI  - Evaluation of live renal donors with three-dimensional contrast-enhanced magnetic
      resonance angiography in comparison to catheter angiography.
AB  - BACKGROUND: Catheter angiography is traditionally used to determine renal
      arterial anatomy in live renal donors. Three-dimensional (3D) contrast-enhanced
      magnetic resonance imaging (MRA) has been suggested as a noninvasive replacement.
      We assessed the possibility of using MRA in live renal donors in Malaysia.
      METHODS: Twenty-six consecutive live renal donors were recruited from 2000 to
      2002. All potential donors underwent evaluation of the renal arteries using both
      techniques. Angiographic findings from both modalities were subsequently compared
      with surgical findings at the time of donor nephrectomy. The total number and
      diameter of the arteries and the presence of early branching and renal
      abnormalities were noted. RESULTS: Both angiographic modalities were able to
      detect multiple renal arteries with catheter angiography having a sensitivity of
      100% and MRA a sensitivity of 97%. MRA missed one 1-mm artery due to a low index
      of suspicion. Renal artery caliber measurements were not significantly different
      between the two methods. However, both techniques tended to overestimate the
      caliber of the renal arteries when compared with measurements taken at surgery.
      Early branching was found in two arteries at the time of surgery, but only one
      was detected by both techniques. Renal cysts seen on MR were not detected by
      catheter angiography. CONCLUSIONS: Our findings suggest that noninvasive MRA is a
      promising substitute for catheter angiography to evaluate the renal arteries of
      live donors.

PMID- 15518698
TI  - Retroperitoneoscopic live donor nephrectomy: extended experience in a single
      center.
AB  - INTRODUCTION: Retroperitoneoscopic live donor nephrectomy (RPLDN) was performed
      because it is considered to be less invasive than open live donor-nephrectomy
      (OLDN) or transperitoneal laparoscopic live donor nephrectomy. PATIENTS AND
      METHODS: Between July 2001 and May 2003, 118 consecutive live donor kidney grafts
      were procured using RPLDN or OLDN. The patients who underwent RPLDN were divided
      into 2 groups: an initial group 1 (n = 38) and a subsequent group 2 (n =
      48).Thirty-two patients who underwent OLDN during the same period were used as
      controls (group 3). The patients were placed in the lateral position. Three
      retroperitoneoscopic ports were inserted. The kidneys were retrieved through a 5
      cm flank incision just below the 11th rib in group 1. In group 2, a 5-cm
      Pfannenstiel incision was used to extract the kidney. RESULTS: The operative time
      was 307 +/- 88 minutes, 245 +/- 42 minutes, and 215 +/- 70 minutes in groups 1,
      2, and 3, respectively (group 1 vs group 2 or 3, P < .01). The mean postoperative
      pentazocine (painkiller) requirements were 12 mg, 4.4 mg, and 22 mg in groups 1,
      2, and 3, respectively (group 2 vs group 1 or 3, P < .01). The hospital stay was
      6.6 +/- 1.6, 4.9 +/- 0.7, and 7.0 +/- 0.1 days in groups 1, 2, and 3,
      respectively (group 2 vs group 1 or 3, P < .01). There were no serious
      complication, such as massive bleeding or bowel injury. CONCLUSIONS: RPLDN may be
      safer and less invasive than open donor nephrectomy.

PMID- 15518699
TI  - Risks and quality-of-life changes in living kidney donors.
AB  - INTRODUCTION: Although the benefits of living donor organs for recipients are
      well documented, the risks and quality-of-life changes in living kidney donors
      are seldom reported. METHODS: From July 1992 to June 2002, all living kidney
      donors underwent regular follow-up at our hospital. The MOS 36-item short-form
      health survey (SF-36), a standardized questionnaire to measure quality of life,
      was used in this study. Furthermore, donor renal function and associate
      complications were assessed. RESULTS: Seventeen donors answered the
      questionnaire, including eight men and nine women of mean age of 41 years (range
      = 25 to 56). No perioperative mortality was noted. No proteinuria or hematuria
      was found during long-term follow-up. The mean serum creatinine level was 0.95 +/
      0.22 mg/dL before the operation. The postoperative mean serum creatinine levels
      at 6 months, 1 year, and 3 years were 1.22 +/- 0.34, 1.19 +/- 0.20, and 1.29 +/-
      0.21 mg/dL, respectively. Two cases underwent scar revision and one complained
      long-term wound pain for more than 1 year. One donor became depressed because of
      graft failure in her son. The SF-36 scores were 84.4 +/- 4.4 (physical function),
      84.0 +/- 4.7 (role-physical), 78.4 +/- 8.0 (body pain), 81.5 +/- 5.9 (general
      health), 83.2 +/- 3.7 (vitality), 83.9 +/- 5.9 (social functioning), 79.9 +/- 4.1
      (role-emotional), and 78.6 +/- 2.3 (mental health), respectively. CONCLUSION: The
      quality-of-life changes and risks after donation are low; most donors are
      concerned about cosmetic problems and pain-related scar formation.

PMID- 15518700
TI  - The influence of brain death on liver in rats.
AB  - OBJECTIVE: Donor brain death produces functional and morphological changes in
      peripheral organs. We examined the influence of brain death on liver function.
      METHODS: Fifty rats were randomly divided into three groups: controls (C), sham
      operated (E1), and brain-dead (E2). All rats underwent tracheotomy with assisted
      respiration. The sera of rats at 1 and 3 hours after brain death were tested for
      the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST),
      hyaluronic acid (HA), and endothelin-1 (ET-1). At the end of assisted
      respiration, liver samples were collected for ultrastructural observation.
      RESULTS: At 1 and 3 hours, the levels of ALT, AST, HA, and ET-1 in group E2 were
      significantly higher than those in groups C and E1 (P < .05). The levels of ALT,
      AST, HA, and ET1 at 3 hours were significantly higher than those at 1 hour (P <
      .05). Under the electronic microscope, Kupffer cells were activated, sinusoidal
      endothelial cells (SEC) denuded, fenestration widened, and hepatocytes under the
      SEC exposed in group E2. In group C and E1, Kupffer cells were not obviously
      activated and SEC were almost intact. CONCLUSIONS: Brain death damages
      hepatocytes and nonparenchymal cells in rat. Endothelin-1 and Kupffer cells play
      an important role in the process. The clearance of hyaluronic acid may provide
      reliable index to judge SEC function after brain death.

PMID- 15518701
TI  - Prevention of primary nonfunction after canine liver allotransplantation: the
      effect of gadolinium chloride.
AB  - PURPOSE: Effective suppression of Kupffer cell function is believed to contribute
      to the prevention of preservation/reperfusion injury. In this study, effect of
      gadolinium, a synthetic Kupffer cell suppressant, on the reperfusion injury was
      examined using a canine partial liver transplantation model. METHODS: About a 70%
      partial liver segment was harvested and reimplanted in a mongrel recipient dog
      weighing 20 to 25 kg. Gadolinium chloride (10 mg/kg) was infused via the cephalic
      vein 24 hours before harvest of the partial liver (gadolinium group, n = 5).
      Serum aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate
      dehydrogenase (LDH), and morphologic grading of graft were compared with those of
      a control group (n = 5). Statistical analysis was done with an independent t
      test. RESULTS: Average total ischemic time was 4 hours and 27 minutes. At 1 hour
      after reperfusion, there were no significant differences in AST, ALP, or LDH
      levels, or pathologic scores. At 48 hours after reperfusion, AST (P = .03) and
      LDH (P = .05) levels were significantly lower in the gadolinium group.
      CONCLUSION: Kupffer cell blockade using gadolinium chloride may be effective to
      reduce ischemia reperfusion injury, but the effect is not evident at an early
      stage of reperfusion.

PMID- 15518702
TI  - On the possible impact of the flushout solution in conditioning livers from non
      heartbeating donors during preservation by gaseous oxygen.

PMID- 15518703
TI  - Pulmonary preservation effect of nitroglycerine in isolated rat lung reperfusion
      model.
AB  - PURPOSE: Though nitric oxide has many favorable protective effects on donor
      lungs, it may also have cytotoxic side effects. In this regard, we investigated
      whether administration of nitroglycerine, a nitric oxide donor, could minimize
      ischemia-reperfusion injury in an isolated rat lung reperfusion model. MATERIALS
      AND METHODS: Thirty-five Sprague-Dawley rats were used for this experiment. The
      nitroglycerine (NTG) group (n = 18) received the drug intravenously and the 17
      control group hosts were treated with the same amount of normal saline. The heart
      lung block was retrieved, weighed, and maintained in University of Wisconsin
      solution for 24 hours at 10 degrees C. Reperfusion was performed using human
      blood diluted in Krebs-Hensleit solution for 60 minutes. Peak inspiratory
      pressure, pulmonary artery pressure, and blood gas analysis were performed. After
      60 minutes of reperfusion, the amount of protein in bronchoalveolar lavage (BAL)
      fluid and the myeloperoxidase (MPO) activity in the lung were measured. RESULTS:
      There were no major statistical differences between the two groups in peak
      inspiratory pressure and pulmonary artery pressure, but the NTG group maintained
      lower pulmonary artery pressure during the whole period of reperfusion. Oxygen
      tension in the NTG group was significantly higher, whereas there were no
      differences in carbon dioxide tension, BAL fluid, protein, or MPO activity.
      CONCLUSION: Administration of NTG before donor lung preservation resulted in
      better lung protection, a possible strategy for clinical application.

PMID- 15518704
TI  - Ultrastructural evaluation of the protective effect of nitroglycerin in
      preservation-reperfusion injury of rat lungs.
AB  - AIM OF STUDY: Nitric oxide (NO) has been reported as a favorable protective
      supplement in donor lung preservation, but related ultrastructural studies are
      rare in the literature. This study was performed to assess the ultrastructural
      changes and to evaluate the protective effect of NO as donor nitroglycerin (NTG)
      treatment of ischemia-reperfusion injury in rat lungs. MATERIALS AND METHODS:
      Fifteen Sprague-Dawley rats weighing 300 to 350 g were used in this study. The
      NTG group (n = 5) used intravenous administration followed by mixture in the
      University of Wisconsin (UW) solution. For the non-NTG group (n = 5), we injected
      the same amount of normal saline intravenously followed by admixture in the UW
      solution. The heart-lung blocks were removed, weighed, and kept in UW solution
      for 24 hours at 10 degrees C. Reperfusion using human blood diluted in Krebs
      Hensleit solution was done for 60 minutes. For the control group (n = 5), we
      injected the same amount of normal saline intravenously, and removed the lungs
      with no preservation and reperfusion procedures. RESULTS: The non-NTG group
      showed multiple patchy areas of alveolar collapse with marked swelling and
      destruction of type I epithelial cells, loss of type II cell surfactant granules,
      endothelial swelling and papillary projection, interstitial edema, and alveolar
      macrophages with active phagocytosis of the destroyed materials. The NTG group
      showed similar ultrastructural changes, but in a lesser severity compared with
      the non-NTG group. CONCLUSION: Administration of the NTG reduced the ischemia
      reperfusion injury in the rat donor lungs. Ultrastructural examination was an
      effective tool to evaluate the protective effect of NTG in ischemia-reperfusion
      procedures of donor lungs.

PMID- 15518705
TI  - The expression of cyclooxygenases and lipoxygenases in renal ischemia-reperfusion
      injury.
AB  - Recent studies of ischemia-reperfusion (I/R) injury have focused on the function
      of neutrophils as well as the actions of inflammatory cytokines. However, few
      reports address cyclooxygenases (COXs) and lipoxygenases (LOXs). We researched
      the expression of COXs (COX-1 and COX-2) and LOXs (5-LOX and 12-LOX) in rat renal
      I/R injury. The right kidney of male Lewis rats was excised, and the left renal
      artery and vein clamped for a 90-minute ischemia time. Rats were humanely killed
      at 0, 1.5, 3, 5, and 12 hours after reperfusion. COX and LOX expressions were
      studied using immunohistostaining. COX-2 and LOX expressions were observed only
      on endothelial cells of normal kidney. From 1.5 to 5 hours after reperfusion, COX
      2 and LOXs expressions gradually intensified on endothelial cells. COX-2 and LOXs
      expression were most intense on endothelial cells at 5 hours after reperfusion.
      Twelve hours after reperfusion, necrosis extended throughout the ischemic kidney
      and nearly all the tubular epithelial cells were destroyed. Thus, at 12 hours
      after reperfusion, COX-2 and LOXs expressions on endothelial cells became weaker.
      However, COX-1 expression was not different at every time after reperfusion. COX
      2 and LOXs were expressed in a rat model showing renal I/R injury. Several hours
      after the maximum of COX-2 and LOXs expressions, the maximal renal I/R injury was
      observed. These results suggest a relationship between COX-2 and LOXs expressions
      and renal I/R injury.

PMID- 15518706
TI  - The effect of a nitric oxide donor on endogenous endothelin-1 expression in renal
      ischemia/reperfusion injury.
AB  - The balance between nitric oxide (NO) and endothelin-1 (ET-1) production is
      essential to the vascular function that controls organ perfusion. Elevated ET-1
      levels in the peritubular capillary network following renal transplantation may
      be associated with renal allograft rejection. Administration of a nitric oxide
      donor during the preischemic period has been shown to protect kidney against
      ischemia-reperfusion injury, but the mechanism underlying this therapeutic
      benefit remains incompletely understood. We hypothesized that early
      administration of the NO donor sodium nitroprusside (SNP) may suppress ET-1,
      thereby improving renal function in an ischemia/reperfusion injury. Sprague
      Dawley rats were subjected to 60 minutes of renal warm ischemia and contralateral
      nephrectomy. Renal biopsies were performed prior to ischemia and reperfusion, and
      at 1 hour and 48 hours after reperfusion. The animals were divided into four
      groups: sham group without warm ischemia; early SNP group (SNP given before
      ischemia); late SNP group (SNP given before reperfusion); and ischemic control.
      ET-1 expression was assessed by semiquantitative analysis with
      immunohistochemical stain using ET-1 monoclonal antibody and hematoxylin-eosin
      staining. Serum creatinine was measured at 48 hours after reperfusion. There were
      significant improvements in all parameters of the early compared with the late
      SNP group and the ischemic control, but there was no difference between the late
      SNP group and the ischemic control. These data suggest that early administration
      of SNP in renal ischemia-reperfusion improves renal function by suppressing ET-1
      expression.

PMID- 15518707
TI  - Study of peroxisome proliferator-activated receptor (PPAR)-gamma in renal
      ischemia-reperfusion injury.
AB  - Recent studies of ischemia-reperfusion (I/R) injury have focused on the function
      of neutrophils, the action mechanism of inflammatory cytokines. However, few
      reports have addressed peroxisome proliferator-activated receptor (PPAR)-gamma.
      PPAR-gamma is a ligand-activated transcriptional factor belonging to the steroid
      receptor superfamily. It plays a role in both adipocyte differentiation and
      tumorigenesis. We researched the expression of PPAR-gamma in renal I/R injury of
      the rat. Male Lewis rats were used. The right kidney was harvested and the left
      renal artery and vein were clamped at 90 minutes of ischemic time. Rats were
      killed at 0, 1.5, 3, 5, and 12 hours after reperfusion. PPAR-gamma expression was
      studied by immunohistostaining. PPAR-gamma expression was observed only on
      mesangial and endothelial cells of normal kidney. From 1.5 to 3 hours after
      reperfusion, PPAR-gamma expression gradually became stronger on mesangial and
      endothelial cells. PPAR-gamma expression was most intense on mesangial cells and
      endothelial cells at 3 hours after reperfusion. Twelve hours after reperfusion,
      necrosis extended throughout the ischemic kidney and nearly all the tubular
      epithelial cells were destroyed, but 12 hours after reperfusion PPAR-gamma
      expression gradually became weaker on mesangial and endothelial cells. PPAR-gamma
      was expressed in the rat model having renal I/R injury. Several hours after
      maximal of PPAR-gamma expression, maximal renal I/R injury was observed. These
      results may indicate a relationship between PPAR-gamma expression and renal I/R
      injury.

PMID- 15518708
TI  - Effect of ligustrazine on ischemia-reperfusion injury in murine kidney.
AB  - INTRODUCTION: Ischemia-reperfusion (I/R) injury is unavoidable in cadaveric renal
      transplantation. It contributes to acute rejection and chronic allograft
      dysfunction. Studies have shown that Ligustrazine, a purified and chemically
      identified component of a Chinese herbal remedy, is a potent blocker of
      vasoconstriction and has strong effects to scavenge oxygen free radicals. Since
      warm I/R is potentially more damaging than cold storage, we investigated the
      possible protective effect of Ligustrazine on warm I/R in mice. METHODS:
      Unilaterally nephrectomized C57BL/6 male mice were subjected to 50 minutes of
      left renal ischemia. Group I were sham-operated animals; group II, nontreated
      animals (saline, iP 30 minutes before I/R); and group III, Ligustrazine-treated
      animals (80 mg/kg, iP 30 minutes before I/R). Mice were sacrificed 24 hours
      postreperfusion. Serum creatinine, blood urea nitrogen, kidney malondialdehyde
      (MDA)level, and superoxide dismutase (SOD) were determined as well as examining
      the kidneys histologically with immunohistochemistry for Bcl-2, and ICAM-1.
      RESULTS: I/R produced a six fold increase in creatinine and urea nitrogen levels
      in group II. Ligustrazine halved the increase, as well as attenuated the necrosis
      and apoptosis in the tubules (P < .01). Ligustrazine decreased MDA levels and
      ameliorated the down-regulation of SOD activity. Bcl-2 was up-regulated following
      I/R, especially in the Ligustrazine-treated group (P < .01). The up-regulation of
      ICAM-1 was greatly diminished by Ligustrazine (P < .01). CONCLUSION: These
      findings suggest that Ligustrazine reduces the renal dysfunction associated with
      warm I/R of the kidney.

PMID- 15518709
TI  - Effects of polyhemoglobin-antioxidant enzyme complex on ischemia-reperfusion in
      kidney.
AB  - INTRODUCTION: The kidney suffers ischemia-reperfusion (I/R) injury during
      transplantation. The purpose of the present study was to investigate the
      therapeutic effect of artificials cells on renal I/R injury through biochemical
      assays and histological examination. METHODS: We prepared artificial cells using
      cross-linked hemoglobin (Hb), superoxide dismutase (SOD), and catalase. Normal
      male Sprague-Dawley rats were divided into 6 groups: the sham-operated control
      group, the group treated with polyHb,and the group treated with polyHb-SOD
      catalase (PSC) (per groups were subjected to ischemia for 1 hour or 2 hours).
      After reperfusion for 4 hours, kidney and blood samples were obtained. RESULTS:
      The levels of SOD and catalase in the PSC group were 15 and 50 times higher than
      those of the control group, respectively. In the polyHb group, the levels of
      blood urea nitrogen (BUN), serum creatinine, renal hydrogen peroxide, and renal
      malondialdehyde were increased. However, their levels were significantly
      decreased by PSC administration. Renal SOD activity did not show any significant
      changes in the polyHb group, but renal catalase activity was decreased by polyHb
      treatment in comparison with the control group. The activities of renal SOD and
      catalase were increased using PSC treatment. In the histological findings, the
      PSC group showed no evidence of acute tubular necrosis in proximal convoluted
      tubules; their microvilli and cytoplasmic microorganelles were relatively well
      preserved. CONCLUSIONS: These results show that PSC effectively reduces renal
      damage via diminished oxygen free radical-mediated injury after I/R.

PMID- 15518710
TI  - Synergistic effect of cold and warm ischemia time on postoperative graft function
      and outcome in human liver transplantation.
AB  - Prolonged cold ischemia time (CIT) during graft preservation and warm ischemia
      time (WIT) during rewarming time have been reported to cause postoperative graft
      dysfunction after orthotopic liver transplantation (OLT). However, the effects of
      both CIT and WIT in combination on patient and graft survivals are not yet
      defined. The aim of this study was to determine whether simultaneously prolonged
      CIT and WIT were associated with early graft outcomes after clinical OLT. For
      analysis of liver graft survival within 90 days of OLT and postoperative graft
      function, 186 consecutive OLT cases were divided into four groups as follows:
      group A, CIT < 12 hours and WIT < 45 minutes; group B, CIT > 12 hours and WIT <
      45 minutes; group C, CIT < 12 hours and WIT > 45 minutes; and group D, CIT > 12
      hours and WIT > 45 minutes. The graft loss rates were 5.4% in group A, 9.8% in
      group B, 11.1% in group C, and 42.9% in group D. The mean highest aspartate
      aminotransferase (AST) value after OLT in group D (3352.3 +/- 569.4 U/L) was
      significantly greater than those in groups A (1411.7 +/- 169.2 U/L) and B (1931.3
      +/- 362.6 U/L). The simultaneously prolonged cold and warm ischemia times
      significantly caused hepatic allograft injury and failure, suggesting some
      cumulative effects of CIT and WIT on postoperative graft function.

PMID- 15518711
TI  - Effect of artificial cells on hepatic function after ischemia-reperfusion injury
      in liver.
AB  - BACKGROUND: The liver suffers from ischemia/reperfusion injury during
      transplantation. Reactive oxygen species generated by xanthine oxidase during
      reperfusion of the ischemic liver may be partially responsible for the hepatic
      injury. Oxygen free radicals are removed by antioxidant enzymes such as
      superoxide dismutase (SOD), catalase, and glutathione peroxidase. Using
      glutaraldehyde and lysine we constructed crosslinked hemoglobin, containing SOD
      and catalase, and assessed its ability to protect against ischemia/reperfusion
      injury during transplantation. METHODS: In contrast to the sham-operated control
      groups, blood was exchanged using crosslinked hemoglobin (polyHb) a PolyHb-SOD
      catalase (PSC) group. After ischemia/reperfusion injury, several parameters of
      hepatic damage and oxygen free radicals were measured as well as microscopic
      examination. RESULTS: Alanine aminotransferase, aspartate aminotransferase,
      superoxide production, hydrogen peroxide, and malondialdehyde levels were higher
      among the PolyHb group than sham-operated controls. The PolyHb group revealed a
      few apoptotic bodies, some acute inflammatory infiltrates in the sinusoids,
      nuclear fragmentations, cell shrinkage, and chromatin clumping with formation of
      apoptotic bodies in the apoptotic cells under microscopic examination. Alanine
      aminotransferase, aspartate aminotransferase, superoxide production, and hydrogen
      peroxide levels were lower in the PSC than the PolyHb group. Hepatic structures
      were well preserved in the PSC group. CONCLUSIONS: Reactive oxygen species
      contribute to hepatic dysfunction with morphologic changes. PSC is effective to
      reduce hepatic damage by lowering oxygen free radical-mediated injury after
      ischemia/reperfusion in the liver.

PMID- 15518712
TI  - Induction of inducible nitric oxide synthase in hepatocytes isolated from rats
      with ischemia-reperfusion injury.
AB  - BACKGROUND: Recent evidence indicates that nitric oxide (NO) has a crucial role
      in hepatic ischemia-reperfusion (I/R) injury. However, little is known about how
      I/R influences the gene expression of inducible nitric oxide synthase (iNOS) in
      hepatocytes. Under inflammatory conditions, we compared the induction of iNOS in
      hepatocytes isolated from normal and I/R-treated rats. METHODS: Hepatocytes were
      isolated using the collagenase perfusion method from rats treated with I/R (30
      minute ischemia of middle and left lobes, followed by 3-hour reperfusion) or sham
      operation (control): Primary cultures of rat hepatocytes were incubated with an
      inflammatory cytokine, interleukin-1beta (IL-1beta), to compare the iNOS
      induction/NO production between the 2 groups. RESULTS: Both control and I/R
      groups had no production of nitrite (a stable metabolite of NO) in the absence of
      IL-1beta. In the control group, IL-1beta stimulated dose- and time-dependent
      production of NO. The I/R group showed more than 2-fold increased levels of NO
      production. Western and Northern blot analyses revealed that the I/R group also
      showed increased levels of iNOS protein and its messenger RNA. CONCLUSION: These
      results suggest that I/R directly affects the inducibility of the iNOS gene in
      hepatocytes by IL-1beta. Increased NO may be associated with protective or toxic
      effects in hepatic I/R injury.

PMID- 15518713
TI  - Synthetic sulfonolipids deduced from sulfonoquinovosyl diacylglycerols of sea
      urchin reduces hepatic ischemia-reperfusion injury in rats.
AB  - BACKGROUND: In hepatic surgery and liver transplantation, ischemia-reperfusion
      (I/R) is an unavoidable process, and protection against hepatic I/R injury is a
      major unresolved problem. In this study, we investigated whether 3-O-(6-deoxy-6
      sulfono-beta-D-glucopyranosyl)-1,2-di-O-acylglycerol bound to saturated C18 fatty
      acids (beta-SQAG9), which was derived from sea urchin intestines, could reduce
      this injury. This agent was recently reported to have immunosuppressive effects
      in allogeneic rat skin grafts. MATERIALS & METHODS: Male Lewis rats were divided
      into two experimental groups. Group 1 rats were injected with SQAG9 (50 mg/kg)
      into the penile vein 15 minutes before the induction of ischemia and into the
      portal vein just reperfusion. The same amounts of normal saline were injected
      into rats in the control group (group 2). Each experimental groups included six
      rats. Seventy percent hepatic ischemia (20 minutes) was induced by occluding the
      blood vessels and bile duct with a vascular clamp. For examination of hepatic
      function, serum levels of aspartate aminotransferase, (AST) alanine transaminase
      (ALT), and lactic dehydrogenase (LDH) were measured. In addition, histological
      examination was also assessed. RESULTS: Three hours after reperfusion, the mean
      plasma concentration of AST, ALT, LDH in group 1 was suppressed compared with
      group 2. Six hours after reperfusion, the hepatic damage in group 1 was mild in
      comparison with that in group 2. CONCLUSIONS: Our data demonstrated that SQAG-9
      reduced the warm hepatic I/R injury.

PMID- 15518714
TI  - The role of ischemic preconditioning in rat liver graft.
AB  - OBJECTIVE: The objective of this study was to investigate the protective effects
      of different modes of ischemic preconditioning (IPC) on an ischemia/reperfusion
      (I/R) injury in rat liver graft. METHODS: A total of 192 Wistar rats were
      randomly allocated into 4 groups, each including 48 rats: control group (C),
      experimental group 1 (E(1)), experimental group 2 (E(2)), and experimental group
      3 (E(3)). IPC was not performed in group C. Among the animals in the experimental
      groups, IPC was performed by blocking blood flow by the portal vein and the
      hepatic artery followed by reperfusion by removal of the clamp before donor liver
      resection: Group E(1), 5-minute ischemia and 10-minute reperfusion; Group E(2), 5
      minute ischemia and 5-minute reperfusion and immediately the same procedure; and
      Group E(3), 10-minute ischemia and 15-minute reperfusion. Liver transplantations
      were performed 4 hours after IPC. At 0.5 hour, 2 hours, 6 hours, and 24 hours
      after portal vein reperfusion recipient blood and graft samples were obtained to
      determine the levels of ALT, AST, TNF-alpha, and apoptosis index (AI). RESULTS:
      At 0.5 hour and 2 hours after portal vein reperfusion, serum tumor necrosis
      factor (TNF)-alpha in the experimental groups (E(1), E(2), and E(3)) was
      significantly lower than in the control group (P < .05). The values in group E(2)
      were significantly lower than those in groups E(1) and E(3) (P < .05). At 24
      hours serum TNF-alpha in group E(2) was significantly lower than groups C, E(1),
      and E(3) (P < .05). At 2 hours and 6 hours, AI values in experimental groups
      (E(1), E(2), and E(3)) were significantly lower than in group C (P < .05). AI in
      group E(2) was significantly lower than that in groups E(1) and E(3) (P < .05).
      At 24 hours, AI values among experimental groups (E(1), E(2), and E(3)) were
      significantly lower than that in the control group (P < .05). CONCLUSION: IPC may
      attenuate liver graft injury by decreasing apoptosis of hepatocytes and
      production of TNF-alpha. The method of IPC with 5-minute ischemia and 5-minute
      reperfusion followed immediately by another cycle of the same procedure was a
      better way to protect a liver graft from I/R injury.

PMID- 15518715
TI  - Pirfenidone protects endotoxin-induced liver injury after hepatic ischemia in
      rats.
AB  - BACKGROUND: Pirfenidone (PFD), an experimental antifibrotic agent, was
      investigated for its effects on endotoxin-induced liver injury after hepatic
      ischemia-reperfusion. METHODS: Male Sprague-Dawley rats were subjected to 30
      minutes of partial hepatic ischemia, followed by reperfusion for 24 hours.
      Lipopolysaccharide (LPS) was injected at 30 minutes of reperfusion. PFD (300
      mg/kg) or its vehicle (0.5% carboxymethylcellulose) was given orally following
      LPS administration. RESULTS: PFD prevented the increase in activities of serum
      alanine transaminase, aspartate transaminase, and lactate dehydrogenase after
      reperfusion. PFD inhibited the increase of cytokine-induced neutrophil
      chemoattractant in serum and liver tissue. The number of neutrophils infiltrating
      the liver was significantly lower in the PFD-treated group than the control
      group. CONCLUSION: These results indicate that PFD prevents endotoxin-induced
      liver injury after hepatic ischemia-reperfusion, in part through the decrease of
      neutrophil infiltration to the liver.

PMID- 15518716
TI  - Effects of pirfenidone on endotoxin-induced liver injury after partial
      hepatectomy in rats.
AB  - BACKGROUND: In living donor liver transplantation, restrictions on graft size are
      a serious obstacle to expand indications for adult recipients. The sequence of
      gram-negative infection, septicemia, and multiple-organ failure is a common cause
      of early mortality after liver transplantation. An effective therapy has not been
      established for endotoxemia following extended hepatectomy in donors or small-for
      size grafts in recipients. Pirfenidone (PFD), a new experimental antifibrotic
      agent, was used to ameliorate on endotoxin-induced liver injury following partial
      hepatectomy. METHODS: Male Sprague-Dawley rats were intravenously administered
      lipopolysaccharide (LPS) 48 hours after 70% hepatectomy. Prior to LPS
      administration, PFD (300 mg/kg) or its vehicle (0.5% carboxymethylcellulose) was
      given orally twice. RESULTS: The survival rate of the PFD-treated group was
      markedly improved compared with that of the controls. PFD prevented the increases
      in the activities of serum enzymes (aspartate transaminase [AST], alanine
      transaminase [ALT], and lactate dehydrogenase [LDH]) and total bilirubin. The
      serum and liver tissue levels of inflammatory cytokines, such as tumor necrosis
      factor-alpha, interleukin-1beta, interferon-gamma, and interleukin-6, were
      significantly lower among the PFD than the control group. Furthermore, the degree
      of necrosis in the remnant liver was significantly decreased in the PFD-treated
      rats compared with controls. CONCLUSION: These results indicate that PFD
      alleviates endotoxin-induced liver injury after partial hepatectomy through the
      inhibition of production of inflammatory cytokines in the residual liver. PFD may
      be useful to prevent endotoxin-induced liver injury after hepatectomy.

PMID- 15518717
TI  - Effect of hepatocyte growth factor on induction of cytokine-induced neutrophil
      chemoattractant in rat hepatocytes.
AB  - BACKGROUND: Restrictions on graft size are a serious obstacle to the expansion of
      indications for adult recipients in living donor liver transplantation.
      Hepatocyte growth factor (HGF) has a crucial role in regeneration following
      hepatic injury. Rat cytokine-induced neutrophil chemoattractant (CINC), a member
      of the interleukin-8 superfamily in humans, has been implicated in chronic liver
      diseases or development of liver ischemia-reperfusion injury. Studies were
      performed to examine whether HGF influences the induction of CINC in hepatocytes.
      METHODS: Primary cultures of rat hepatocytes were treated with or without
      recombinant human (rh) HGF. The release of CINC into the culture medium and
      levels of CINC mRNA were measured using an enzyme-linked immunosorbent assay and
      Northern blot analysis. Transcription of nuclear factor (NF)-kappa B was detected
      by electrophoretic mobility shift assays. RESULTS: rhHGF increased the release of
      CINC in the medium dose- and time-dependently, showing a maximal effect at 100
      ng/mL. Genistein (100 mumol/L) blocked the release of CINC stimulated by rhHGF.
      Levels of CINC mRNA were also increased, reaching a maximum at 8 hours after
      addition of rhHGF. Electrophoretic mobility shift assays revealed rhHGF activated
      transcription factor, NF-kappa B. CONCLUSION: These results suggest that HGF
      stimulates the induction of CINC gene expression through activation of NF-kappa
      B. CINC may be involved in the function of HGF during liver regeneration.

PMID- 15518718
TI  - Effect of pirfenidone on induction of chemokines in rat hepatocytes.
AB  - BACKGROUND: Hepatic ischemia-reperfusion results in a neutrophil-dependent liver
      injury. The process of neutrophil recruitment and activation in this injury is at
      least partially dependent on the induction of chemokines, such as cytokine
      induced neutrophil chemoattractant (CINC) and macrophage inflammatory protein-2
      (MIP-2) in rats. In the liver, parenchymal cells (hepatocytes), in addition to
      nonparenchymal cells such as Kupffer cells, have been reported to produce
      chemokines in the regulation of hepatic inflammation. Pirfenidone (PFD) is a new
      experimental drug used as an antifibrotic agent. Studies were performed to
      determine whether PFD influences the production of CINC and MIP-2 stimulated by
      interleukin (IL)-1beta in a primary culture model of rat hepatocytes. METHODS:
      Primary cultures of rat hepatocytes were treated with IL-1beta in the presence
      and absence of PFD. The protein and mRNA of CINC and MIP-2 were analyzed using
      enzyme-linked immunosorbent assays and Northern blots. RESULTS: IL-1beta
      increased the release of CINC and MIP-2 into culture media in a dose- and time
      dependent manner. PFD inhibited both CINC and MIP-2 release in dose-dependent
      fashion. However, PFD had no effect on the levels of CINC mRNA induced by IL
      1beta. CONCLUSION: These results suggest that PFD inhibits the production of CINC
      and MIP-2 by IL-1beta at a posttranscriptional step in hepatocytes.

PMID- 15518719
TI  - Fibronectin protects endotoxin-induced liver injury after partial hepatectomy in
      rats.
AB  - Endotoxemia following extended hepatectomy may be a cause of postoperative death.
      Multiple organ failure related to septemia is a common cause of early mortality
      after liver transplantation. Fibronectins (Fns) are involved in cellular
      adhesion, motility, differentiation, apoptosis, hemostasis, wound healing, and
      ischemic injury. Studies were performed to determine whether Fn influences the
      survival rate of rats subjected to endotoxin-induced liver injury after partial
      hepatectomy. Male Sprague-Dawley rats were intravenously administered
      lipopolysaccharide (LPS) 48 hours after 70% hepatectomy. Prior to LPS
      administration, plasma Fn or bovine serum albumin was given intravenously. The
      survival rate of the Fn-treated group was higher than that of the controls. Fn
      prevented increases in serum enzyme activity and total bilirubin related to liver
      injury. The levels of inflammatory cytokines including tumor necrosis factor
      alpha, interleukin-1beta, and interleukin-6 interferon-gamma were also
      significantly lower in the Fn-treated than the control group. Furthermore, the
      number of apoptotic cells and the degree of necrosis in the remnant liver were
      significantly decreased in the Fn-treated rats compared with controls. These
      results indicate that Fn prevents endotoxin-induced liver injury after partial
      hepatectomy, at least in part through inhibiting the production of inflammatory
      cytokines, and the necrosis apoptosis in the remaining liver.

PMID- 15518720
TI  - Attenuation of canine warm ischemic small bowel injury by novel combination of
      nitric oxide donor, FK409, and cytokine suppressive anti-inflammatory agent
      FR167653.
AB  - Organ ischemia-reperfusion injury is caused by two consecutive steps,
      microcirculatory disturbance and neutrophil-endothelial cell interactions, which
      are caused by inflammatory cytokines. We examined the hypothesis that combination
      therapy with a donor (FK409) of nitric oxide, one of the potent mediators with
      diverse roles as a vosodilator and a platelet inhibitor, together with the
      cytokine suppressor agent (FR167653) attenuates warm ischemic injury in canine
      small bowel. Small bowel ischemia was initiated by clamping the superior
      mesenteric artery and vein. Animals were divided into two groups: a control group
      (n = 5) subjected to 2-hour small bowel ischemia only, and a combination therapy
      group (FK/FR group, n = 5) that received FK409 (300 mcg/kg/h) plus FR167653 (1
      mg/kg/h) intravenously before and after the ischemic event. We evaluated animal
      survival, small bowel tissue blood flow, and enzyme release from the small bowel.
      All controls died from severe acidosis within 2 days and all the FK/FR animals
      survived 7 days (P < .05). The FK/FR group recovered more than 70% of blood flow
      immediately after the revascularization, while the flow was less than 40% among
      the controls. Serum creatine phosphokinase values in the control group after
      reperfusion were significantly higher than those in the FK/FR group. In
      conclusion improvement of the microcirculation by FK409 and inhibition of
      cytokine release by FR167653 together attenuated warm ischemic small bowel
      injury.

PMID- 15518721
TI  - Etiology of cardiovascular diseases in the transplant population: will the choice
      of immunosuppressant matter?

PMID- 15518722
TI  - Low-grade lymphoma: the optimal timing.
AB  - The median survival of patients with follicular lymphoma (FL), the most frequent
      low-grade non-Hodgkin's lymphoma, is 7 to 10 years with most patients exhibiting
      a pattern of relapsing disease and increasing drug resistance. The subset with
      poorest prognostic features, however, has a median survival of less than 2 years.
      The failure of conventional chemotherapy to cure such patients has led to the
      evaluation of high-dose therapy (HDT) and hemopoietic stem cell transplantation.
      Although no large randomized trials have been performed, historical comparisons
      within individual centers as well as registry analysis appear to support HDT with
      autologous stem cell support in patients with relapsed and refractory FL.
      Appropriate patient selection on the basis of prognostic markers as well as
      transplantation earlier in the course of the disease have been identified as key
      issues that predict the success of transplantation in these patients. HDT with
      autologous support as part of planned initial therapy or in first remission has
      also been the subject of a number of studies including at least two large
      randomized trials. Although preliminary analyses suggest an advantage in the HDT
      approach, longer follow-up will be required before definitive conclusions can be
      drawn. A variety of purging strategies have been evaluated for autologous
      transplants but results are still inconclusive. Allogeneic transplantation is an
      option for selected patients, although its wider application is restricted by
      transplant-related complications. Experience with nonmyeloablative conditioning
      strategies is limited, and as yet the expectation of a reduction of transplant
      related morbidity and mortality remains to be demonstrated.

PMID- 15518723
TI  - Management of pregnancy in transplant recipients.
AB  - Transplantation offers the best prospect of pregnancy in fertile women with
      various types of end-stage organ disease. Based on data from the USA National
      Transplantation Pregnancy Registry, >70% of posttransplant pregnancies have a
      successful live birth. Greatest experience has been seen in transplants involving
      the kidney, followed by the liver and then heart. Most pregnancies do not affect
      graft function significantly but are associated with significant obstetric
      problems such as spontaneous abortions, premature deliveries, low birthweight,
      intrauterine growth retardation, preeclampsia, etc. Cesarian section is required
      in 30% to 50% of patients, due to obstetric or maternal concerns. Neonatal death
      is rare, but 30% to 50% of live births have complications. Thus, management
      requires a multidisciplinary team. Similar data have been documented in developed
      Asian countries such as Japan and Singapore. Although fertility is restored early
      (<6 months), the current recommendation is to wait for >/=1 year, if not 2 years,
      after transplantation before allowing pregnancy. Patients without evidence of
      graft dysfunction and hypertension are more likely to have successful outcomes.
      Acute rejections may occur but the incidence does not appear to be increased
      dramatically. Treatment should be to similar to that of nonpregnancy treatment.
      Further pregnancies may be considered in instances of good outcome for the graft,
      fetus, and mother. Significant experience and safety has been accumulated in
      treatment using cyclosporine, azathioprine, prednisolone, and tacrolimus.
      However, few data are available with regard to the newer immunosuppressants, such
      as mycophenolate mofetil, and thus these agents are not recommended. Most live
      births have normal growth and development. Although there is much information
      available on posttransplant pregnancy it is imperative that each center maintains
      its own registry of pregnancy and offspring outcomes.

PMID- 15518724
TI  - Spectrum of severe infections in an Asian renal transplant population.
AB  - Infections in renal transplant recipients (RTX) account for 26% of
      hospitalization days annually and 40% of overall mortalities. A retrospective
      study of infections requiring hospitalization occurring among 725 Asian RTX in
      2002 was performed. RESULTS: Serious infections requiring at least one
      hospitalization occurred in 9.2% of RTX (n = 67). Multiple pathogens affected
      28.4% of patients, resulting in 118 infectious episodes during 93
      hospitalizations. Mean age of affected patients was 48 years and female to male
      ratio was 2:1. Forty-one (61.2%) had impaired renal function (serum creatinine
      >141 mumol/L). Mean duration of hospitalization per patient was 17 days and the
      in-patient mortality rate was 17.9% eighty-one (87%) hospitalizations were for
      late infections (>6 months posttransplant). Cyclosporine (CsA) with prednisolone
      with or without azathioprine was the immunosuppressant in 62.7% (n = 42) of RTX
      but proportionally, infections were more frequent among RTX on other more potent
      immunosuppressants (n = 21; 7.4% CsA-based vs. 19.3%, potent, P < .05).
      Bacterial, viral, fungal, and Pneumocystis carinii infections comprised 64.4%,
      20.3%, 5.9%, and 4.2% respectively. Urinary tract infection, pneumonia, and
      bacterial septicemia (35.52%, 31.6%, and 11.8%, respectively) were the major
      presentations. E. coli, cytomegalovirus (CMV), and Candida were the most common
      pathogens. Notably, 13 out of 18 (72.2%) viral CMV infections were co-
      infections, occurring together with bacterial infections. CONCLUSIONS: Late
      infections with the use of potent immunosuppressives and concurrent CMV
      reactivation are a major cause of morbidity. Longer antibacterial prophylaxis and
      closer monitoring for CMV infections may help reduce morbidity.

PMID- 15518725
TI  - Role of patient-support groups in the Thailand transplant program.
AB  - Thailand started kidney transplantation in 1972 when vascular and nonvascular
      transplant programs were first established. Presently, we have 27 kidney, 6
      liver, and 6 intrathoracic private or governmental transplantation centers, all
      approved and members of the Organ Donation Centres Thai Red Cross Society (ODC).
      They also provide organ procurement teams to the ODC. The Thai Medical Council
      has issued and supervised the criterion of brain death and ethical rules of
      transplantation to all practicing physicians since 1989. All recipients must
      register at these selected transplantation centers and at the ODC. When the
      potential donor arrives from any hospital in Thailand, the donor hospital
      notifies the ODC and organ procurement teams are sent out to harvest organs and
      transfer them to the recipient transplantation centers. The ODC computerizes and
      shares organs according to ABO, HLA typing, and crossmatching results. After
      transplantation all patients register with the Thai Transplantation Society (TTS)
      and the ODC. The TTS, the Thai Transplant Coordinator Society, and the ODC are
      responsible for the education of surgeons, physicians, nurses, patients, the
      public, and mass media to improve our transplant program. Bone marrow
      transplantation has separate regulations. Pooled, nonrelated bone marrow donors
      are registered at the blood-bank of the Thai Red Cross Society to provide donors
      for bone marrow transplantation. Financially, government support recipients only
      if they are state enterprise workers or civil servants. Public fund support
      through the ODC for organ procurement and the Kidney Foundation of Thailand is
      available for kidney transplantation. The ODC and the transplantation centers are
      the main patient-support groups for transplant programs in Thailand.

PMID- 15518726
TI  - Effect of panel-reactive antibody positivity on graft rejection before or after
      kidney transplantation.
AB  - INTRODUCTION: Because it is well known that kidney transplant recipients with
      preformed lymphocytotoxic antibodies against HLA antigens have increased graft
      rejection rates, a serological crossmatch is routinely performed before kidney
      transplantation. But, the presence of these antibodies is not routinely monitored
      after transplantation. We investigated the panel-reactive antibody (PRA) response
      to know whether variations before or after kidney transplantation were associated
      with graft rejection. METHODS: We prospectively analyzed sera from 350 renal
      allograft recipients from September 1998 to March 2003. Pretransplantation and
      posttransplantation sera at 3 or 5 weeks postoperatively were tested in PRA.
      Recipients were stratified into 3 groups according to their PRA levels group I,
      PRA = 0; group II, PRA = less than 50%, and group III, PRA = more than 50%.
      RESULTS: The total graft rejection rate among 350 recipients was 9.4% (n = 33).
      Twenty-four pretransplantation PRA-positive recipients had a graft rejection rate
      of 20.8% (n = 5), compared with an 8.6% (n = 28) rate among 326
      pretransplantation PRA-negative recipients. Six of 24 posttransplantation PRA
      positive recipients (25%) experienced a graft rejection versus 27 (8.3%) of 326
      posttransplantation PRA-negative subjects. Among the pretransplantation PRA
      stratae, the rejection rate in group III was 25% (1 of 4) versus 20% (4 of 20) in
      group II and 8.6% (28 of 326) in group I (P < .05). According to the
      postransplantation PRA level, 37.5% (3 of 8) in group III versus 18.8% (3 of 16)
      in group II and 8.3% (27 of 326) in group I (P < .05) had a graft rejection.
      CONCLUSION: Our study suggests that the PRA response pretransplantation and in
      the early posttransplantation period correlates with the kidney allograft
      rejection rate.

PMID- 15518727
TI  - Laparoscopic simultaneous bilateral pretransplant nephrectomy for uncontrolled
      hypertension.
AB  - Severe hypertension resistant to multiple antihypertensive drugs represents an
      indication for bilateral pretransplant renal ablation by surgery or
      angioembolization. Besides causing severe pain and renal postinfarction syndrome,
      angioembolization may be ineffective. We present our experience with simultaneous
      bilateral laparoscopic pretransplant nephrectomies in patients with end-stage
      renal disease and severe uncontrollable hypertension. Among the three patients
      considered for bilateral pretransplant laparoscopic nephrectomy between September
      2002 and August 2003, the procedure was successfully performed in two patients.
      Left nephrectomy was performed transperitoneally and right nephrectomy
      retroperitoneoscopically. In one of the three patients, a prior attempt at
      angioembolization had produced a dense perirenal reaction, rendering laparoscopic
      surgery impossible. Total operating time for bilateral laparoscopic nephrectomies
      was 260 and 280 minutes. Within 1 month following the nephrectomies, all patients
      became normotensive with minimal or no antihypertensive medications. We conclude
      that simultaneous bilateral laparoscopic nephrectomy is feasible and less morbid
      in end-stage renal disease patients. Prior angioembolisation can make
      laparoscopic surgery difficult or impossible.

PMID- 15518728
TI  - Renal replacement therapy options from an Indian perspective: dialysis versus
      transplantation.
AB  - In developing countries such as India, the management of end-stage renal disease
      (ESRD) is largely guided by economic considerations. In the absence of health
      insurance plans, fewer than 10% of all patients receive renal replacement therapy
      (RRT). Hemodialysis (HD) is mainly a short-term measure to support ESRD patients
      prior to transplant. Infections are common in dialysis patients. The majority of
      patients starting HD die or are forced to abandon treatment because of cost
      constraints within the first 3 months. The cost of peritoneal dialysis (PD) is
      two times higher than that of HD, fewer than 2% of patients are started on PD.
      Among the three RRT options available, renal transplant is the preferred mode, as
      it is most cost-effective and provides a better quality of life. But due to
      financial constraints and nonavailability of organs, only about 5% of ESRD
      patients undergo transplant surgery. Though the removal of organs from brain-dead
      patients has been legalized, the concept of donation of organs from deceased
      donors has not received adequate social sanction. Only 2% of all transplants are
      performed from deceased donors. Due to limited access to RRT, the ideal approach
      should be to reduce the incidence of ESRD and attempt preventive measures.
      Preemptive transplant, reducing the duration of dialysis prior to transplant, use
      of immunosuppression for only up to 1 year, and availability of more deceased
      donor organs may be helpful to make RRT options within the reach of the common
      man.

PMID- 15518729
TI  - Influence of donor and recipient gender on early graft function after living
      donor kidney transplantation.
AB  - Long-term effects of donor and recipient gender on the outcome of living donor
      kidney transplantation have been examined but the impact on early graft function
      is less certain. In this study, we analyzed age, gender, body weight, height,
      body surface area (BSA), and lean body weight (LBW) of both donors and
      recipients. Preoperatively we collected 24-hour urine samples to measure
      creatinine excretion from donor and postoperatively we determined when the
      recipient serum creatinine (Scr) reached baseline levels. Variables included were
      ischemic times, kidney graft weight, duration of dialysis, cause of end-stage
      renal disease (ESRD), degree of HLA match, and mismatch, types of
      immunosuppression (cyclosporine or FK506, dual or triple), and episodes of acute
      rejection. The variables were analyzed by independent sample t tests and chi
      square statistics using SPSS. Values of P < .05 were considered significant. Male
      patients of both donors and recipients were significantly taller and heavier
      (higher BSA and LBW) than female. Urinary 24-hour creatinine excretion was
      greater in male patients whether donors or recipients. There were no statistical
      differences in graft weight or creatinine clearance based on the gender of the
      donor or recipient. The creatinine of male donors or recipients was higher than
      that of females. The other variables were not significantly different. In
      conclusion, the effect of donor or recipient gender on early graft function
      depends on the metabolic demands, which are higher in male recipients.

PMID- 15518730
TI  - Transplantation of pediatric cadaveric kidneys into adult or pediatric
      recipients.
AB  - In Japan, nationwide cadaveric organ sharing for kidney transplantation by the
      Japan Organ Transplant Network (JOTN) has operated since April 1995. This study
      retrospectively analyzed the long-term results of single pediatric donor kidneys
      transplanted into adult or pediatric recipients at a single center. From March
      1983 to December 2002, 281 cadaveric renal allografts were transplanted at our
      center, including, 17 recipients of cadaveric kidneys from donors aged less than
      16 years. We divided these 17 recipients into two groups: 10 adult recipients
      (group 1; G1) and seven pediatric recipients (group 2; G2). HLA-AB, -DR
      mismatches were 1.3 +/- 1.3, 0.7 +/- 0.5 in G1 and 2.6 +/- 1.3, 1.4 +/- 0.8 in
      G2, respectively (P < .05 for both). The end of the observation of this study was
      March 2003. Among G1, two recipients died with functioning grafts and one died
      after graft loss. Among G2, no recipients died. Patient survival rates at 1 and 5
      years were 90% and 80% in G1 and 100% and 100% in G2, respectively. At the end of
      the observation in this study, five recipients among G1 and six recipients among
      G2 had functioning grafts. Graft survival rates at 1 and 5 years were 90% and 80%
      in G1 and 85.7% and 85.7% in G2, respectively. Our results demonstrate that
      transplantation of pediatric cadaveric kidneys into pediatric recipients was
      excellent compared to adult recipients in terms of survival. Priority to
      pediatric patients should be given especially in cases of pediatric donors.

PMID- 15518731
TI  - Comparison of survival probabilities for living-unrelated versus cadaveric renal
      transplant recipients.
AB  - Any attempt to improve organ donation would be of benefit due to the growing
      shortage of cadaveric sources for transplantation. OBJECTIVE: We compared the
      graft survivals and possible predictive variables among renal transplant
      recipients with organs from living unrelated (LURD) versus cadaveric donors (CD).
      METHOD: Among 104 consecutive renal transplants performed from July 1992 to
      February 2003, 41 were from LURD and 24 from CD. Immunosuppressive regimens were
      based on cyclosporine and steroids with mycophenolate mofetil added after 1998.
      Patient and graft survivals were estimated using the Kaplan-Meier method and
      compared using log-rank tests. The significance level of predictive variables was
      analyzed with the Cox proportional hazard model. The follow-up period was 2 to
      127 months (median 46 months). RESULTS: Eight recipients lost their grafts (six
      from LURD and two from CD) due to four chronic rejections, one acute rejection,
      one recurrence of primary disease, and one death with a functioning graft. The
      graft survival rates at 1, 3, 5, and 7 years were 97.6%, 91.9%, 88.5%, and 82.2%
      for LURD transplants versus 95.5%, 90.9%, 90.9%, and 90.9% for CD transplants,
      respectively (P > .05). Delayed graft function and donor age (>55 years old) were
      statistically significant predictors of graft survival among LURD transplants.
      Donor age (>55 years old) and multiple preoperative transfusion history were
      significant in CD transplants. CONCLUSION: LURD transplant survival was similar
      to that of CD transplants in our series. LURDs are an excellent source of organs
      to expand the donor pool.

PMID- 15518732
TI  - Risk factors on graft survival of living donor kidney transplantation.
AB  - Living donors have always been the basic resources of transplantation in our
      country, where cadaveric harvesting is still hampered for various reasons.
      OBJECTIVE: The aim of this study was to compare graft survival rates between
      living unrelated donor (LURD) and living related donor (LRD), to assess the
      potential risk factors for the graft survival, and to discuss the role of LURD.
      METHOD: From October 1991 to February 2003, 77 living donor renal transplants
      were performed: 41 were LURD and 36 were LRD transplants. The analyzed variables
      were donor relationship, recipient age and sex, donor age and sex, HLA-DR
      mismatching, nonspecific blood transfusion history of donor, acute rejection
      episodes, repeated rejection episode (more than 3 times), delayed graft function,
      recurred primary disease, and immunosuppressive regimen. Graft survival rate was
      assessed with the Kaplan-Meier method and the significance of possible variables
      with the Cox proportional hazard model. RESULTS: Eleven recipients lost their
      grafts (6 from LURD and 5 from LRD), most of them are due to chronic rejection (n
      = 7). Overall 3-, 5- and 10-year graft survival in live donors were 92.8%, 86.6%,
      and 76.9%, respectively. Graft survival at 3, 5, and 10 years being 91.9%, 88.5%,
      and 74.7% for the LURD versus 94%, 84%, and 78.8% for LRD transplants (P > .05).
      Acute rejection episodes, especially more than 3 times (risk ratio [RR] = 11.1)
      and preoperative multiple transfusion history (RR = 4.2) were significant factors
      on graft survival in our series. CONCLUSION: Acute rejection episodes markedly
      decreased the long-term graft survival in live donor renal transplants. The use
      of LURD transplants provides graft survival comparable with LRD transplants and
      proper management to acute rejection is essential for long-term graft survival.

PMID- 15518733
TI  - Analysis of cause of death with a functioning graft: a single-center experience.
AB  - INTRODUCTION: After the introduction of new immunosuppressants, such as
      tacrolimus and mycophenolate mofetil, we have achieved excellent results for
      kidney transplantation with a low acute rejection rate. Currently,
      nonimmunological factors are considered to be the main cause of graft loss for
      long-term transplant patients. In this study, we analyzed the cause of death with
      a functioning graft. PATIENTS AND METHODS: We performed 1375 cases of living
      kidney transplantation (LKT) and 219 cases of cadaveric kidney transplantation
      (CKT) between January 1983 and December 2002. Of these patients, 86 LKT patients
      and 19 CKT patients died with a functioning graft. RESULTS: The mean duration of
      graft function was 4.8 +/- 4.5 years. The incidence of the causes of death were:
      infection, 24%; stroke, 17%; cardiovascular disease, 16%; malignant disease, 15%;
      hepatic failure, 11%; gastric ulcer, 4%; and accident/suicide 2%. Five- and 10
      year graft survivals for LKT were 80.2 and 62.0%, respectively. The corresponding
      values for patients (with the exception of the patients who died with a
      functioning graft) was 83.0% and 66.1%, respectively. The 5- and 10-year graft
      survival rates for cadaveric kidney transplants were 70.8% and 48.9%,
      respectively. The corresponding values for patients (with the exception of the
      patients who died with a functioning graft) were 75.3% and 52.6%, respectively.
      CONCLUSION: To prevent death with a functioning graft, management of vascular
      disorders such as stroke and cardiovascular disease, malignant disease, and
      infectious disease is crucial for kidney transplant patients.

PMID- 15518734
TI  - Quality of life in cadaver and living-related renal transplant recipients in
      Kuala Lumpur hospital.
AB  - OBJECTIVE: To examine the quality of life in cadaver (CAD) and living-related
      (LRRT) renal transplant recipients. METHODS: A cross-sectional study was done on
      patients followed in renal transplant clinic from 1/4/03 to 1/7/03 using the SF
      36 questionnaire. Inclusion criteria were age >16 years,minimum of 3 months'
      posttransplant, and informed consent. Exclusion criteria were current treatment
      for rejection or infection or any life-threatening conditions. Information on
      duration of transplant, duration of dialysis prior to transplant, number of co
      morbidities, and sociodemodraphic data were collected. RESULTS: Sixty-four among
      110 patients (58.1%) completed the SF36 questionnaire. The LRRT recipients were
      younger, had a longer duration of transplant, and had spent significantly less
      time on dialysis prior to transplant compared to CAD transplant patients.
      Overall, the physical composite and the mental composite scores were not
      significantly different between the two transplant groups. Age was negatively
      associated with the physical composite score (Spearman's rho -0.251, P < .05) and
      bodily pain (Spearman's rho -0.266, P < .05). Duration of dialysis prior to
      transplant was negatively correlated with social functioning (Spearman's rho 
      0.28, P < .05) and mental health (Spearman's rho -0.39, P < .005). In multiple
      regression analysis, age was a significant predictor of the SF36 physical
      composite score (P < .05). CONCLUSION: This study shows that the quality of life
      between LRRT and CAD recipients was not significantly different. Increased age
      was associated with poorer physical capacity.

PMID- 15518735
TI  - Outcome of renal transplantation in children with pericardiopleural effusion.
AB  - INTRODUCTION: Children with end-stage renal disease may present with
      pericardiopleural effusion secondary to volume overload and overhydration. The
      present study was designed to investigate the efficacy and safety of renal
      transplantation in these pediatric patients. METHODS: From 1981 to 2001, six of
      20 patients (30%) under 18 years old who received renal transplants showed
      pericardiopleural effusion after serial pretransplant imaging studies. These
      patients also displayed associated diseases, such as congestive heart failure (n
      = 3), ascites (n = 2), and splenomegaly (n = 2). The recipients included five
      boys and one girl of mean age of 12.7 years (range, 8 to 17 years), all of whom
      had undergone hemodialysis before transplantation. The waiting time for grafts
      ranged from 1.3 to 6 years (mean = 2.6 years). Episodes of acute pulmonary edema
      had been observed in three patients pretransplant. RESULTS: One recipient died
      with a functioning graft due to heart failure with acute pulmonary edema at 4
      months after transplantation. Acute rejection episodes were observed in three,
      and chronic rejection in two children. The median follow-up was 11 years (range =
      6 to 16 years) in the other five recipients, all of whom presently survive with
      functioning grafts. The posttransplant mean serum creatinine levels at 1 year, 3
      years, and 5 years were 1.54 +/- 0.44, 1.74 +/- 0.56, and 1.92 +/- 0.56 mg/dL,
      respectively. CONCLUSION: Renal transplantation in children displaying
      pericardiopleural effusion was associated with a high success rate. However,
      these patients must be followed closely with regular cardiopulmonary evaluation
      since their condition may deteriorate.

PMID- 15518736
TI  - Graft survival analysis in kidney transplantation: a 12-year experience in a Thai
      medical center.
AB  - INTRODUCTION: To analyze graft survival and to find the factors that influence
      survival in kidney transplantation recipients, we performed an analytic
      retrospective study. METHODS: A retrospective analysis was undertaken on records
      of all patients who underwent transplantation from December 25, 1990 to December
      24, 2002. Survival studies were calculated using the Kaplan-Meier method. The
      outcome endpoints were death, redialysis, lost to follow-up, and study
      termination. RESULTS: One hundred thirty-eight operations (49 living-related
      kidney transplantations [LRKT] and 89 cadaveric kidney transplantations
      [CDKT])were recruited. Age of patients was 39.9 +/- 9.8 years (range, 9-57
      years). The male to female ratio was 1.9:1. The waiting time was 24.25 +/- 25.2
      months. Only 9 recipients had diabetes mellitus. The graft survival rate of the
      cadaveric group was slightly higher than the living related group: 90.65% vs
      87.48%, 88.97% vs 85.05%, 83.04% vs 79.72%, and 76.65% vs 67.78% at 1, 2, 3, and
      4 years, respectively (P = .94). Age, sex, waiting time, modality of dialysis,
      diabetes mellitus, ischemia time, HLA-mismatch, 2 DR-mismatch, delayed graft
      function (DGF), and body mass index (BMI) had no influence on graft survival.
      Acute rejection had a negative influence on graft survival in both the LRKT group
      (P = .09) and the CDKT group (P = .015). Patients who received cyclosporine
      (CSA), prednisone (Pred), and mycophenolate mofetil (MMF) showed better graft
      survival than ones on CSA, Pred, and azathioprine (Aza) (P = .18). CONCLUSION:
      There was no significant difference in graft survival between the LRKT and CDKT
      groups. In this study, only acute rejection was demonstrated to have negative
      influence on survival rates in CDKT. The timing of transplantation may play a
      major confounding factor on the results.

PMID- 15518737
TI  - Prognostic factors affecting graft and patient survival in cadaveric and living
      kidney transplantation.
AB  - Numerous studies have reported various prognostic factors that affect graft and
      patient survival in living and cadaveric donor kidney transplantation (KT). The
      purpose of this study was to evaluate the clinical outcomes and prognostic
      factors affecting graft and patient survivals in living and cadaveric donor KT.
      Between February 1995 and December 2001, 421 patients who had undergone cadaveric
      donor KT (group I: 216 cases, 51.3%) or living donor KT (group II: 205 cases,
      48.7%), were retrospectively analyzed. Five-year overall graft survival rates in
      living was significantly better than that in cadaveric donor KT, respectively (P
      = .0234). There was no difference in patient survival rates between the two
      groups. Such factors as absence of rejection, female donor, female recipient,
      adult KT according to recipient age (>14 years), and donor serum creatinine level
      just before transplantation (< 2.5 mg/dL) were significantly associated with good
      graft survival among cadaveric donor KT, whereas two factors-absence of rejection
      and adult KT according to recipient age (>14 years)-influenced graft survival in
      living donor KT. In multivariate analysis, the only significant prognostic factor
      related to graft survival was the presence of rejection. In conclusion, we
      suggest that the presence of rejection is the only factor that impairs graft
      survival in both cadaveric and living donor KT, while other factors affected
      graft survival differently in the two groups.

PMID- 15518738
TI  - The impact of sex and age matching for long-term graft survival in living donor
      renal transplantation.
AB  - BACKGROUND: Deficient functional renal mass leads to progressive renal injury
      owing to the detrimental effects of glomerular hyperfiltration. Therefore, renal
      transplant mass is an important determinant of outcome. MATERIALS AND METHODS: We
      retrospectively analyzed 614 living donor renal transplantations performed from
      1979 to 2002. Patients were divided into 4 groups according to donor-recipient
      gender differences: group 1 (male to male), group 2 (male to female), group 3
      (female to male), and group 4 (female to female). We analyzed the clinical and
      immunological data to compare the 4 groups with respect to long-term graft
      survival, age gender, acute rejection episodes an HLA matching. We used the
      Kaplan-Meier method with the log-rank test to assess graft survival. RESULTS: The
      actuarial graft survival rate was 86.24% at 5 years for donors younger than 50
      years of age compared with 73.15% for those older than 50 years (P = .0000). The
      graft survival from younger donors than recipients was 85.23% at 5 years compared
      with 80.35% for older donors (P = .0213). The graft survival of group 3 (female
      donor to male recipient) was 75.12% at 5 years compared with 85.72%, 85.33%, and
      83.16% for groups 1, 2, and 4, respectively (P = .0165). The main parameters
      significantly associated with graft survival were donor age (P = .0000), acute
      rejection episode (P = .0000), donor gender (P = .0215). HLA-DR matching (P =
      .0516), and donor and recipient age matching (P = .0213). CONCLUSIONS: The
      results suggest that the sex and age matching between donors and recipients
      should be considered as a criterion in the choice of donor and recipient pairs
      for living donor renal transplantation.

PMID- 15518739
TI  - The impact of donor and recipient age on the outcome of kidney transplantation.
AB  - BACKGROUND: As survival has improved in the general population over the last few
      decades, the age of patients participating in renal transplantation has also
      increased. This study sought to investigate the impact of donor and recipient age
      as predictors of long-term graft survival in renal transplantation. MATERIALS AND
      METHODS: We analyzed transplantation outcomes in 598 patients who received renal
      transplants from 1979 to 2002. Patients were divided into 4 groups according to
      their age at renal transplantation. Group A (donor age <50 years, recipient age
      >50 years, n = 19/3.2%); group B (donor age >50 years, recipient age <50 years, n
      = 153/25.5%); group C (donor age <50 years, recipient age >50 years, n =
      69/11.6%), and group D (donor age <50 years, recipient age <50 years, n =
      357/59.8%). Univariate analysis to assess the effect of donor and recipient age
      as predictor factors of graft outcome was complimented by Kaplan-Meier and log
      rank methods to assess graft survival with P < 1.05 considered significant.
      RESULTS: In the elderly donor group, graft survival was 92.8% at 1 year and 85.6%
      at 3 years; in the younger donor group, they were 93.4% and 90.2%, respectively,
      a difference that was statistically significant (P = .02). Univariate analysis of
      age factors showed a significant reduction in graft survival among recipients who
      received kidneys transplants from donors older than 50 years, although recipient
      age >50 years was not found to be an independent risk factor. The incidence of
      acute rejection was 24.6% in the elderly donor group and 23.5% in the younger
      donor group (P = not significant). Among the 4 groups, the best result was group
      D with 1-year and 3-year graft survival rates of 93.3% and 90.5%, respectively,
      but this result was not statistically significant. CONCLUSIONS: These results may
      help the design for transplantation strategies for kidneys procured from elderly
      donors and for allocation to elderly recipients.

PMID- 15518740
TI  - Comparison of patient survival between various subgroups among renal transplant
      patients: a single center experience.
AB  - OBJECTIVES: To compare patient graft survival between various subgroups among
      renal transplant patients. PATIENTS AND METHODS: A retrospective analysis of all
      renal transplant patients from January 1, 1993, to June 1, 2003, was performed
      using follow-up records and data submitted to the National Renal Registry.
      RESULTS: A total of 91 renal transplant patients were followed, with a male-to
      female ratio of 57:34 (62.6%:37.4%) and mean age at transplant 35.6 +/- 12.1
      years (range 10.1-64.4 years) with 38 (41.8%) cases transplanted locally and 53
      (58.2%) cases transplanted overseas, of which 36 (39.6%) were from live donors
      and the remaining 55 (60.4%) from cadavers. As of June 1, 2003, 50 transplant
      patients are on regular follow-up, with 41 patients lost due to 12 (29.3%)
      deaths, 16 (39.0%) graft failures, 11 (26.8%) transfers, and 2 (4.9%) lost to
      follow-up. Overall patient and graft survival rates at 2, 5, and 10 years were
      93.1%, 77.4%, and 49.2%, respectively. Survival rates for male transplant
      patients were 91.4%, 71.9%, and 46.7% compared to 96.1%, 86.9%, and 53.6% for
      females. Survival rates for Malay race patients were 92.0%, 59.5%, and 28.6%;
      Chinese rates were 96.0%, 81.6%, and 54.8%, and Indian rates were 81.0%, 81.0%,
      and 46.3%, respectively. The survivals for transplants from living donors were
      96.9%, 85.6%, and 62.3% compared to cadaveric kidney transplants namely 89.9%,
      71.3%, and 35.0%. The local transplant survival rates were 96.9%, 82.3%, and
      60.8% compared to overseas transplants, with survival rates of 89.9%, 73.5%, and
      35.7%. Finally, living-related donor transplantation survival rates were 96.8%,
      84.9%, and 62.2% compared to nonrelated donors-90.1%, 71.3%, and 35.0%-at 2
      years, 5 years, and 10 years, respectively. CONCLUSION: Overall survival has been
      good. The survival rates were better among female gender, Chinese race, local
      transplantation, and kidneys from living-related donors.

PMID- 15518741
TI  - Effect of posttransplant anti-HLA antibody on outcome of renal transplantation.
AB  - Pretransplant anti-HLA antibody has an impact on renal transplantation (RT)
      outcome. However, the role of posttransplant anti-HLA antibody in renal allograft
      outcome remains unclear. We conducted this study to determine whether
      posttransplant anti-HLA plays an important role in the outcome of renal
      allografts. Our investigation used a cross sectional design. Class I and II anti
      HLA antibodies were obtained in 41 renal transplant patients. Patients had
      undergone either living-related (n = 15) or cadaveric (n = 26) RT. All patients
      had been transplanted for >6 months. The correlation of posttransplant class I
      and class II, anti-HLA antibodies with renal allograft function glomerular
      filtration rate (GFR) was analyzed. Patients displaying a GFR of >60 mL/min
      showed positive anti-HLA antibody status for class I (n = 2) and class II (n =
      9). In contrast, those whose renal transplants showed a GFR <60 mL/min included
      three patients positive for HLA class I and 19 patients for HLA class II.
      Posttransplant class II anti-HLA antibody showed a negative correlation with GFR
      (r = -0.31, P = .03). Preliminary results indicated that class II posttransplant
      anti-HLA antibody might be one mechanism of chronic renal allograft rejection and
      may confirm the important role of HLA matching in renal transplantation outcome.

PMID- 15518742
TI  - Sirolimus (rapamycin) reduces the incidence of acute rejection episodes in renal
      transplantation: an initial experience in Taiwan.
AB  - BACKGROUND: Acute rejection is the major cause of graft loss in renal
      transplantation. Sirolimus (rapamycin) inhibits the effects of cytokines on T and
      B cells; therefore, it provides prophylaxis against acute renal rejection. This
      open-label trial assessed the incidence of biopsy-confirmed acute rejection
      episodes, variation in renal function, as well as graft and patient survival
      rates up to 12 months posttransplantation when using sirolimus in combination
      with cyclosporine and prednisolone as immunosuppressants. METHODS: Ten kidney
      transplant recipients received sirolimus 2 mg daily after a 6-mg loading dose.
      Doses were then adjusted to keep the whole-blood trough level between 5 and 20
      mg/mL. All patients received sirolimus in combination with cyclosporine and
      prednisolone. RESULTS: At 12 months after renal transplantation, the graft and
      patient survival rates were 90% and 90%, respectively. One patient died at 2
      months due to sepsis with a functioning graft. The mean serum creatinine levels
      at 1, 3, and 6 months were 1.59 mg/dL, 1.71 mg/dL, and 1.65 ml/dL, respectively.
      There was no biopsy-confirmed acute rejection episode within 12 months.
      CONCLUSIONS: Sirolimus in combination with cyclosporine and prednisolone
      significantly protected kidney transplant recipients from acute rejection for up
      to 1 year of follow-up.

PMID- 15518743
TI  - Sirolimus in chronic allograft nephropathy.
AB  - Chronic allograft nephropathy (CAN) is the most common cause of late renal
      transplant loss. Calcineurin inhibitor (CNI) nephrotoxicity is known to
      contribute to CAN. A sirolimus-based regimen way allow for early CNI reduction or
      elimination. The aim of the present study was to determine the efficacy and
      safety of a sirolimus-based regimen for CAN. From December 2001 to August 2003,
      kidney transplant (KTx) recipients with CAN were enrolled for treatment with
      sirolimus. Among 32 studied patients, 24 (75%) underwent graft biopsy before the
      initiation of sirolimus. Baseline maintenance immunosuppression consisted of
      cyclosporine/tacrolimus and prednisone with or without mycophenolate mofetil. The
      follow-up duration on sirolimus therapy was 8.5 +/- 5.9 months (range: 1 to 22
      months). The average dosage of sirolimus was 1.8 +/- 0.5 mg/d at the end of
      follow-up. The mean trough level of sirolimus was 5.1 +/- 2.1 ng/mL. Sirolimus
      was effective in 16 (50%) patients while 3 (9.4%) patients improved (serum
      creatinine [Cr] decrease > 10%) and 13 (40.6%) maintained stable (change of serum
      Cr within 10%). Sirolimus was effective in 5 (35.7%) patients whose serum Cr was
      over 3.0 mg/dL but failed to rescue all four patients whose serum Cr was over 4.0
      mg/dL. Eleven (68.8%) of 16 responders showed a reduction (29.8% +/- 13.8%) in
      CNI dosage. The most common adverse events were hyperlipidemia (37.5%), anemia
      (25%), and diarrhea (21.8%). Twelve patients discontinued sirolimus due to graft
      failure (4), severe infection (3), stroke related mortality (1), anemia (2),
      diarrhea (1), and edema (1). In conclusion, sirolimus is effective in 50% of KTx
      recipients with CAN, especially when the serum Cr is less than 3.0 mg/dL.
      However, the increased incidence of infection, diarrhea, and hyperlipidemia are
      of major concern.

PMID- 15518744
TI  - Is sirolimus a safe alternative to reduce or eliminate calcineurin inhibitors in
      chronic allograft nephropathy in kidney transplantation?
AB  - PURPOSE: We evaluate whether cyclosporine (CsA) or tacrolimus (FK) could be
      reduced or eliminated after sirolimus was added in chronic allograft nephropathy
      (CAN). By reducing doses of CsA or FK, we expected that renal function would
      improve. METHOD AND MATERIAL: Twenty-one patients with CAN had sirolimus added as
      an immunosuppressive agent. We evaluated the creatinine (Cr) level 3 months after
      addition. The doses of CsA and FK were decreased gradually and then eliminated
      over a course of 4 to 6 weeks. If the Cr level rose rapidly or other prominent
      signs of rejection occurred; low-dose CsA or FK would be added per protocol. We
      evaluated the duration of engraftment before sirolimus and the Cr level when it
      was added. RESULTS: Renal function improved in 13 of 21 cases. The improvement in
      Cr ranged from 12.5% maximally to 1.84% minimally. Seven of 13 cases still
      required low-dose CsA. The average duration of engraftment before sirolimus was
      13.66 +/- 10.80 months. The average Cr level before sirolimus was 1.65 +/- 0.56
      mg/dL. In the other eight cases, the Cr level kept rising from 5.1% to 20.4%. The
      average duration of engraftment was 88.38 +/- 42.21 months. The average Cr level
      before sirolimus was 2.85 +/- 0.54 mg/dL. Hyperuricemia was noted in 31.3% and
      hyperlipidemia in 68.8%. CONCLUSION: Sirolimus is a safe alternative to reduce or
      eliminate CsA or FK in CAN. In cases with a long duration of engraftment and high
      Cr level, sirolimus might have some effect as a substitute for CNI and thus
      prevent further nephrotoxicity.

PMID- 15518745
TI  - Pharmacokinetic variability of sirolimus in Taiwanese renal transplant
      recipients.
AB  - To evaluate the pharmacokinetic variability of sirolimus (Rapamycin, SRL) in our
      renal transplant (RTx) recipients, dose-normalized trough concentration (C(0)) of
      SRL, and their intrasubject coefficients of variation (%CV) were analyzed. Thirty
      eight patients were enrolled in regimens containing SRL. Concomitant
      immunosuppression included steroids (n = 38), cyclosporine (n = 33), tacrolimus
      (n = 3), and mycophenolate mofetil (n = 7). The mean dose-normalized C(0) was
      2.13 +/- 0.91 ng/mL/mg. The intrasubject %CV of the dose-normalized C(0) ranged
      from 14% to 88% and averaged 42% in our series. The mean dose-normalized C(0) of
      SRL in our RTx recipients was much lower than that reported in Phase III trials.
      The intrasubject variation of dose-normalized C(0), even after administrating SRL
      for 6 months, could still be quite prominent. Thus, we suggest that, to maintain
      adequate therapeutic concentrations, periodic (monthly or bimonthly) SRL C(0)
      measurement is necessary in Taiwanese (Oriental) patients receiving SRL.

PMID- 15518747
TI  - Pharmacokinetics of mycophenolic acid after a single and multiple oral doses of
      mycophenolate mofetil in Chinese renal transplant recipients.

PMID- 15518746
TI  - Selective use of mycophenolate mofetil in renal transplant patients in Indian
      scenario.
AB  - PURPOSE: Although mycophenolate mofetil (MMF) has emerged as a valuable
      immunosuppressive in renal transplantation, its high cost demands that it be used
      selectively. MATERIALS AND METHODS: This retrospectively study included 55 renal
      transplant patients on MMF for rescue therapy after treatment of acute vascular
      rejection (n = 45), acute/chronic liver disease with elevated transaminases (n =
      4), early chronic rejection (n = 2), cyclosporine toxicity (n = 3), and
      cyclosporine-induced hemolytic-uremic syndrome (n = 1). The patients were given
      1.5 to 2 g MMF in divided doses for at least 6 months, depending upon the
      tolerability, adverse effects, and finances, and followed for 1 year. The
      patients on MMF following treatment of acute rejections were compared with
      controls who received azathioprine-based triple immunosuppression after treatment
      of an acute rejection episode. RESULTS: The incidence of recurrent acute
      rejection in the first year was 18% in the MMF group compared to 42% in the
      control group (P < .005). The serum transaminases in the acute/chronic liver
      disease group reached normal levels at 3 to 6 months. The serum creatinine
      remained stable for a mean duration of 8 months in the early chronic rejection
      patients. The patients with cyclosporine toxicity showed stable graft function on
      low-dose cyclosporine. The patient with hemolytic-uremic syndrome showed stable
      graft function for 4 years. The MMF-based triple regimen is two times more
      expensive than an azathioprine-based regimen. CONCLUSION: MMF significantly
      decreases the recurrence of acute rejection. It is a good alternative agent in
      special situations like acute/chronic liver diseases with elevated transaminases,
      early chronic rejection, cyclosporine toxicity, and cyclosporine-induced
      hemolytic-uremic syndrome. Because of the high cost it should be used selectively
      in our population.

PMID- 15518748
TI  - Safety of mycophenolate mofetil versus azathioprine in renal transplantation: a
      systematic review.
AB  - INTRODUCTION: To evaluate the safety of mycophenolate mofetil (MMF) versus
      azathioprine (Aza) in renal transplantation, we compared their side effects using
      evidence-based methods. METHODS: Medline, Embase, Cochrane library, and Chinese
      Biomedicine database (CBM) were searched to select randomized clinical trials
      that had one group using MMF and another group using Aza as an immunosuppressive
      drugs. Safety analysis consist of the following factors: diarrhea, abdominal
      pain, vomiting, nausea, constipation, CMV infection, leukopenia, anemia,
      thrombocytopenia or skin malignancy. RevMan 4.11 software was used for the
      systematic review analysis. RESULT: Twenty trials including 6387 patients were
      identified. The diarrhea incidence with MMF (3 g/d) was higher than for Aza at 1
      and 3 years (P < .05). Diarrhea on MMF (2 g/d) was higher than for Aza within 6
      months (P < .05). CMV infection incidence on MMF (3 g/d) was higher than for
      Aza's at 3 years (P < .05), but MMF (2 g/d) did not show a statistical
      significance compared with Aza. Leukopenia incidence on MMF (3 g/d) was higher
      than that on Aza, whereas the incidence with MMF (2 g/d) was not significantly
      different from Aza. Skin malignancy incidence showed no statistical difference
      between MMF 3 g/d, MMF 2 g/d, or Aza. CONCLUSION: The use of MMF is associated
      with slight increases in gastrointestinal adverse effects, some hematologic
      adverse events, and CMV infections compared with Aza. Larger sample sizes of
      randomized controlled trials are needed to evaluate the safety of MMF.

PMID- 15518749
TI  - Efficacy of mycophenolate mofetil versus azathioprine after renal
      transplantation: a systematic review.
AB  - INTRODUCTION: Our objective was to evaluate the efficacy of mycophenolate acid
      (MMF) versus azathioprine (AZA) after renal transplantation. MATERIALS AND
      METHODS: The following electronic databases were searched: Medline, Embase,
      Cochrane library, and Chinese Biomedicine database (CBM). Randomized controlled
      trials (RCTs) were subjected to Revman 4.11 for statistical analyses. RESULTS:
      Twenty-three RCTs were identified to compare MMF and AZA for antirejection,
      prophylaxis after renal transplantation. The data showed that MMF (2 g/d) was
      more beneficial than AZA to improve graft and long-term patient survivals, but
      there was no statistical differences between MMF (3 g/d) and AZA. Whether at 6
      months or at 1 year after renal transplantation, the use of MMF (2 g/d) or MMF (3
      g/d) markedly reduced the incidence of biopsy-proven rejection. CONCLUSION:
      Compared with AZA, MMF is a more potent immunosuppressive drug, that is more
      efficient in reducing the incidence of acute rejection episodes after renal
      transplantation. MMF can improve the graft and patient survival rate. The 2 g per
      day dosage is more acceptable.

PMID- 15518750
TI  - Clinical experience of mycophenolate mofetil in the treatment of chronic
      allograft nephropathy in kidney transplantation: three-year follow-up.
AB  - BACKGROUND: Mycophenolate mofetil (MMF) in conjunction with calcineura
      antagonists has been shown to prevent acute rejection in renal allograft
      recipients. Its role in treatment of chronic rejection or allograft nephropathy
      is still controversial. We initiated the study to investigate the effect of
      adding MMF to a cyclosporine plus prednisolone regimen in renal recipients with
      chronic allograft nephropathy. MATERIALS AND METHODS: We retrospectively studied
      36 patients with chronic allograft nephropathy, defined clinically as increased
      of serum creatinine, proteinuria, and hypertension. Renal function, cyclosporine
      level, renal biopsy, and renal scan were regularly done as indicated. MMF was
      added to 20 recipients after initial treatment with cyclosporine and
      prednisolone. The other 16 recipients were managed without adding MMF. Serum
      creatinine was monitored for 3 years. RESULTS: The demographic characteristics of
      the patients in the two groups were comparable. The average dose of prednisolone
      was unchanged throughout the study and the trough level of cyclosporine was
      maintained in the range of 100 to 150 ng/mL. The serum creatinine decreased
      initially in the group on MMF, but renal function deteriorated progressively
      after 6 months. There was a difference in serum creatinine between the two groups
      but this did not reach statistical significance. CONCLUSION: MMF therapy tender
      to improve renal function initially but did not attenuate significantly the
      impairment in chronic allograft nephropathy.

PMID- 15518751
TI  - The pharmacokinetics of mycophenolate mofetil in Thai kidney transplant
      recipients.
AB  - Mycophenolate mofetil, in addition to cyclosporine and prednisolone significantly
      reduces the rate of acute rejection. The original recommended dose of MMF is
      fixed at 2 g/day. However, Thai patients cannot tolerate this dose due to
      gastrointestinal adverse effects. So the majority of patients are maintained on
      MMF at doses ranging from 0.5 to 2 g/day, according to their tolerability with an
      acceptable rate of acute rejection episodes. This study sought to determine the
      steady state pharmacokinetics of MMF in Thai kidney transplant recipients on
      stable doses of MMF. Forty-six kidney transplant patients more than 3 months on a
      stable MMF dose of 0.5, 1, 1.5, and 2 g/day together with cyclosporine and
      prednisolone underwent a single pharmacokinetic blood sampling for 12 hours
      following the morning dose of MMF. The analysis of plasma concentrations of
      mycophenolic acid (MPA), the sole pharmacologically active metabolite of MMF, was
      performed by using an high performance liquid chromatography method. Sparse
      efficient sampling strategies were employed to optimize the blood sampling
      schedule. Hence, blood samples were collected at 0, 0.5, 2, 12 hours after the
      MMF dose. The sampling time was designed to best estimate AUC(0-tau) at steady
      state. The initial MPA-Bayesian estimator were used for MPA concentrations that
      would allow the best estimation of Vc, CLt, and Ka. In this study, there is a
      high interindividual variability in the AUC. The median MPA AUC was 34.3 ug.h/mL
      (range 14.1-65.4). Thirty-one of 45 (68.9%) patients had a MPA AUC within 20 to
      40 ug.h/mL, which is the most reasonable risk: benefit ratio in terms of
      preventing acute rejection episodes. Forty-one of 45 (91.1%) patients had MPA AUC
      within 20 to 60 ug.h/mL, which is the MPA therapeutic range. The highest Pearson
      correlation coefficient of determination between MPA AUC and a single
      concentration was observed with MPA 2 hours (r = 0.622) Without a fixed dosing
      regimen, most Thai kidney transplant recipients who receive MMF as part of a
      maintenance immunosuppressive regimen have the MPA AUC within the therapeutic
      window. The single drug concentration that correlates well with the AUC is MPA at
      2 hours postdose.

PMID- 15518752
TI  - Correlation of mycophenolic acid pharmacokinetic parameters with side effects in
      Chinese kidney transplant recipients treated with mycophenolate mofetil.

PMID- 15518753
TI  - Primary immunosuppression with tacrolimus in kidney transplantation: three-year
      follow-up in a single center.
AB  - INTRODUCTION: The 1-year results of the phase III US Multicenter Trial comparing
      tacrolimus- and cyclosporine (Sandimmun)-based immunosuppressive therapy in
      kidney transplantation revealed a significant reduction in the incidence and
      severity of acute rejection episodes among patients maintained on tacrolimus.
      This retrospective, nonrandomized, single-center study represented 3-year data
      for patient and graft survival and safety in the tacrolimus-treated patients.
      METHODS: Among 97 consecutive kidney transplant recipients 41 who received
      tacrolimus and 56 cyclosporine-based immunosuppression were followed for 3 years
      for patient and graft survivals and for the incidence of acute rejection episodes
      as well as serious adverse events. RESULTS: The 3-year patient and graft survival
      rates for tacrolimus and cyclosporine were similar (91.0% vs 90.2%, 96.5% vs
      95.0%). However, the incidence of acute rejection episodes was significantly
      lower in the tacrolimus (17.1%) compared with the cyclosporine group (35.7%, P =
      .043). There was a higher incidence of headache, posttransplant diabetes, and
      alopecia reported in the tacrolimus group, whereas hypertension,
      hypercholesterolemia, and hirsutism were more frequent in the cyclosporine group.
      The incidences of hand tremor, hyperkalemia, and viral infections were comparable
      in both groups. Two patients in the tacrolimus group were converted to
      cyclosporine due to nephrotoxicity and posttransplant diabetes, respectively,
      whereas 12 patients in the cyclosporine group were converted to tacrolimus as
      rescue therapy for acute rejection (41.7%), gingival hyperplasia (33.3%),
      nephrotoxicity (8.3%), neurotoxicity (8.3%), and hirsutism (8.3%), respectively.
      CONCLUSION: The 3-year results of tacrolimus treatment show excellent efficacy
      and safety in kidney transplantation. Due to different side-effect profiles, it
      is necessary to develop individualized immunosuppressive strategies in kidney
      transplant recipients.

PMID- 15518754
TI  - Primary immunosuppression with tacrolimus and low-dose mycophenolate mofetil in
      renal transplant recipients.
AB  - Both tacrolimus and mycophenolate mofetil (MMF) are potent immunosuppressive
      agents used in combination for prevention of acute rejection in renal
      transplantation. We studied the efficacy and safety of tacrolimus/MMF-based
      primary immunosuppression as well as their pharmacokinetics (PK) in Chinese renal
      transplant recipients. Oral tacrolimus was initiated at about 0.2 mg/kg/d, dose
      which was adjusted to achieve target trough levels of 10 to 20 ng/mL at 3 months
      and 5 to 10 ng/mL thereafter. The patients also received MMF (0.5 g bid) and
      prednisolone. PK profiles were studied at 1 week, and 1, 3, and 6 months
      posttransplant. Blood samples were taken at 0 (predose), 20, 40, 60, 75, and 90
      minutes and 2, 4, 6, 8, 10, and 12 hours postdose for each profile. Plasma MPA
      and whole blood tacrolimus levels were determined by HPLC and EMIT methods
      respectively. Eight patients were studied with mean follow-up of 16.1 +/- 2.4
      months. One patient (12.5%) experienced a borderline acute rejection episode.
      Both 1-year graft and patient survival rates were 100%. Posttransplant diabetes,
      diarrhea, and hand tremor occurred in 12.5%, 12.5%, and 37.5%, respectively. No
      patient had an opportunistic infection. Tacrolimus trough concentrations showed a
      fair correlation with AUC(0-12h) (R(2) = 0.587). Mean MPA AUC values at 1, 3, and
      6 months were 40.5 +/- 9.4, 44.4 +/- 17.3, and 57.2 +/- 20.7 mug*h/mL,
      respectively (P = .0486, n = 7). In conclusion, primary immunosuppression with
      tacrolimus, low-dose MMF (0.5 g bid), and prednisolone is effective and safe with
      adequate systemic MPA exposure in renal transplant recipients.

PMID- 15518755
TI  - Results of kidney transplantation in patients receiving MMF- or MMF and
      basiliximab-containing immunosuppression.
AB  - Mycophenolate mofetil (MMF) is a more potent immunosuppressive drug than
      azathioprine or mizoribine in combination with cyclosporine (CsA) and steroids.
      Recently, basiliximab (BA), an interleukin-2 receptor antagonist, has become
      available in Japan. The purpose of this study was to evaluate the efficacy of an
      extremely low CsA dose immunosuppressive protocol with MMF versus MMF plus BA
      after renal transplantation (RTx). PATIENTS: Between September 2001 and March
      2003, we performed 79 RTx with CsA-based immunosuppression, including nine from
      cadavers and 70 from living donors with 15 ABO-incompatible RTx.
      Immunosuppression consisted of methylprednisolone (MP), CsA and MMF (group 1; n =
      24) versus added BA during the induction phase (group 2; n = 55). In group 2, MP
      was withdrawn on postoperative day 14. Supplementary MP, muromonab-CD3, or
      gusperimus was administered if rejection was suspected clinically or diagnosed by
      biopsy. RESULTS: The incidence of biopsy-proven acute rejection (AR) was
      significantly higher among group 1 than group 2 patients (P < .05). CsA C2 levels
      in group 1 were significantly higher than group 2 at each time (P < .01). The
      incidence of infection was comparable. Patient and graft survival rates in group
      1 were 100% and 100%; in group 2, they were 98% and 98%, respectively.
      CONCLUSION: The short-term results of RTx were favorable in both the MMF, and the
      MMF plus BA immunosuppression. In addition, BA significantly reduced the number
      of AR episodes. Early steroid withdrawal in recipients receiving BA induction was
      not associated with an increased risk of AR.

PMID- 15518756
TI  - Conversion from mycophenolate mofetil to azathioprine in high-risk renal
      allograft recipients on cyclosporine-based immunosuppression.
AB  - OBJECTIVE: In a randomized control trial of mycophenolate mofetil (MMF) versus
      azathioprine (AZA) with cyclosporine and steroids, we demonstrated that MMF
      reduced acute rejection (AR) among renal allograft recipients (RTX) who were of
      low to moderate risk. However, 10% had AR when converted from MMF to AZA at 6
      months, postrenal transplantation (RT). Two clinical markers, abnormal serum
      creatinine (SCr) and proteinuria at 6 months, post-RT, were associated with AR
      postconversion. The present study examined the safety of such conversion in
      selected high-risk RTX at 1 year of MMF therapy. METHODS: Thirteen high-risk RTX
      receiving MMF for either high panel reactive antibody (n = 9) or following AR (n
      = 4), with normal SCr and no proteinuria at 1 year, were selected for conversion.
      The incidence of AR, adverse events, and renal parameters (SCr, creatinine
      clearance, proteinuria) at 6 months postconversion was evaluated. Eight high-risk
      RTX who did not meet these selection criteria were retrospectively reviewed and
      used as controls. RESULTS: Renal parameters (SCr 123 +/- 26 vs 129 +/- 27
      mumol/L; pre- vs postconversion) were not significantly different; no episodes of
      AR or proteinuria were documented. Azathioprine was discontinued in two patients
      due to leukopenia. In the control group, one patient had graft loss from chronic
      rejection, whereas one developed posttransplant lymphoproliferative disease
      necessitating MMF withdrawal. CONCLUSION: These results suggest that selective
      conversion from MMF to AZA after 1 year is safe, even in high-risk RTX. Normal
      SCr and absence of proteinuria are good screening parameters to identify patients
      at low risk for AR following such conversion.

PMID- 15518757
TI  - Effects of and predictors for tacrolimus rescue therapy among renal transplant
      patients under cyclosporine-based immunosuppression.
AB  - BACKGROUND: Though cyclosporine has dramatically decreased rejection rates and
      improved graft survival rates of renal allografts, there is still a remarkable
      rate of acute rejection and progressive deterioration of renal function after
      transplantation. Rescue therapy with tacrolimus has been used for allografts
      failing under cyclosporine-based treatment in order to get some renal functional
      recovery or stabilization. The aim was to evaluate tacrolimus rescue therapy for
      failing allografts under cyclosporine-based immunosuppression for possible
      prediction factors for success. PATIENTS AND METHODS: Thirty-five renal allograft
      recipients with failing transplants under cyclosporine-based immunosuppression
      were enrolled into this study. Renal function was evaluated by reciprocal serum
      creatinine level (1/Cr) and calculated CCr. The slope of changes in 1/Cr and CCr
      were calculated before and after tacrolimus therapy. The possible risk factors
      that affect the outcome of tacrolimus rescue therapy were analyzed. RESULTS:
      Nineteen patients showed improved renal function (group 1) and 16 patients,
      persistent deterioration (group 2) after rescue therapy. Group 1 showed positive
      slopes of changes of 1/Cr and CCr after rescue therapy. Group 2 patients showed
      persistent negative slopes although less negative than before rescue therapy.
      Only the posttransplant time was the significant predictive factor for successful
      tacrolimus therapy (P = .018). CONCLUSION: Tacrolimus rescue therapy improved or
      stabilized renal function in some patients with failing grafts under cyclosporine
      based immunosuppression. To assure a successful rescue effect, it should be given
      early after transplantation, if there is a tendency toward deterioration of renal
      function.

PMID- 15518758
TI  - Increased tacrolimus trough levels in association with severe diarrhea, a case
      report.
AB  - It is well known that during diarrhea episodes decreased cyclosporine and
      tacrolimus levels are often observed, usually requiring an increase in dose. An
      increase in tacrolimus trough levels is infrequently recognized as a potential
      cause of the adverse effect of severe diarrhea. Herein, we report the case of a
      renal transplant patient who displayed increased tacrolimus trough levels during
      an episode of gastroenteritis with severe diarrhea. The patient is 32-year-old
      male who received a renal transplant from his mother. Immunosuppression was
      initiated with tacrolimus in combination with mycophenolate mofetil and
      prednisone. The postoperative course was uneventful. The function of the
      transplanted kidney was normal. Eight months after transplantation he presented
      to our hospital with a history of high fever, abdominal pain, nausea and severe
      diarrhea. He was admitted with a diagnosis of enterocolitis of unknown etiology.
      The blood trough level of tacrolimus had increased from 6.7 ng/mL to 28.7 ng/mL
      after the onset of diarrhea. A therapeutic trough level of tacrolimus was reached
      6 weeks after complete relief of diarrhea. Tacrolimus shows large variability in
      bioavailability after oral administration, both due to intestinal metabolism by
      cytochrome P450 (CYP3A4) and active secretion from enterocyte into intestinal
      lumen by P-glycoprotein. The epithelial cells of the intestine, may be destroyed
      abrogating P-glycoproteins during the course of enterocolitis, thereby increasing
      the levels of tacrolimus. It is recommended to monitor trough levels of
      tacrolimus during severe diarrhea of any nature to prevent tacrolimus-related
      complications.

PMID- 15518759
TI  - Randomized trial of tacrolimus versus cyclosporine in steroid withdrawal in
      living donor renal transplant recipients.
AB  - The introduction of new immunosuppressants has prompted trials of steroid
      withdrawal. However, several groups have reported a higher incidence of
      rejection. We conducted a randomized two-arm, parallel-group, open-label,
      prospective study to compare steroid withdrawal (at 6 months posttransplant) from
      the regimens of tacrolimus + mycophenolate mofetil (MMF) (FK group) versus
      cyclosporine + MMF (CSA group). The entry criteria were recipients of first
      living donor transplants with no diabetes mellitus (DM), congestive heart
      failure, chronic liver disease, or acute rejection within 6 months
      posttransplant. The primary endpoint was a biopsy-proven acute rejection episode
      or treatment failure within 1 year posttransplant. While 87 recipients were
      assigned to FK (n = 43) and CSA groups (n = 44) before transplantation, 76
      recipients (FK 39, CSA 37) could be tapered off steroids at 6 months
      posttransplant, since 11 were excluded due to acute rejection within 6 months
      posttransplant (FK two, CSA three) or protocol violations (FK two, CSA four).
      After steroid withdrawal, the incidence of acute rejection episodes was 0% in the
      FK group and 13.5% in the CSA group (P < .05). Other results at 12 months
      posttransplantation were comparable: the incidences of DM 7.8% versus 0% (FK
      group vs CSA group), hypercholesterolemia 41.0% versus 59.5%, hypertensives 48.7%
      versus 59.6% as well as the levels of plasma creatinine 1.21 +/- 0.24 versus 1.31
      +/- 0.50 mg/dL (P > .05 in every variable). These data suggest that steroid
      withdrawal is successful in first living donor renal transplant recipients.
      Tacrolimus may be significantly more effective than cyclosporine to prevent acute
      rejection after steroid withdrawal.

PMID- 15518760
TI  - C4d-positive acute humoral renal allograft rejection: rescue therapy by
      immunoadsorption in combination with tacrolimus and mycophenolate mofetil.
AB  - OBJECTIVE: We investigated the efficacy of immunoadsorption (IA) in combination
      with tacrolimus (FK506) and mycophenolate mofetil (MMF) rescue therapy for C4d
      positive acute humoral rejection (AHR) of renal transplants. METHODS: Six of 185
      cadaveric renal allograft recipients developed AHR at a mean of 4.8 +/- 0.8 days
      after the operation. C4d deposits were observed in peritubular capillaries (PTC)
      with accumulation of granulocytes. IA with staphylococcal protein A and FK506-MMF
      combination therapy were administered. RESULTS: After treatment with IA for 6.3
      +/- 1.03 sessions combined with FK506 (0.14 to 0.16 mg.kg(-1).d(-1)) and MMF (1.5
      g/d) therapy, renal function recovered in all the patients. The mean duration of
      treatment to a serum creatinine decrease was 14 +/- 2.9 days. The pre-IA panel
      reactive antibody reactivity (PRA) peaked at 50.2% +/- 6.1%, and was
      significantly reduced to 8.3% +/- 2.9% after IA. In four of six patients repeat
      allograft biopsy revealed a remission of AHR. With a mean follow-up of 18.8 +/-
      5.46 months, patient and allograft survival are 100% and renal function remains
      stable with a mean serum creatinine of 1.2 +/- 0.22 mg/dL. CONCLUSION: The
      optimal treatment for alloantibody-mediated AHR remains uncertain. Our findings
      suggest that a therapeutic approach combining IA and FK506-MMF rescue improves
      the outcome of AHR.

PMID- 15518761
TI  - Role of postdose cyclosporine monitoring in living renal transplant recipients.
AB  - Achieving optimal cyclosporine (Neoral) absorption is critical for successful
      graft outcome. Recently there have been studies on postdose monitoring of
      cyclosporine. Two- and 3-hour postdose cyclosporine levels measured by
      radioimmunoassay were correlated with occurrence of rejection and cyclosporine
      nephrotoxicity in 30 patients; C(2) and C(3) levels were significantly lower than
      the desired therapeutic levels in patients with acute rejection. Based on our
      study and those of others we suggest C(3) levels should be adopted in clinical
      practice.

PMID- 15518762
TI  - Evaluation of cyclosporine C2 levels in long-term stable renal allograft
      recipients.
AB  - BACKGROUND: The use of cyclosporine was traditionally monitored by the trough
      level (C(0)). However, the immunosuppressive effects of cyclosporine correlate
      with its drug exposure, represented by the area under curve (AUC). It was also
      noted that cyclosporine C(0) level correlated with AUC poorly, while C(2) level
      (concentration at 2 hours after drug administration) satisfactorily correlated
      with AUC. Most recent studies concern the use of C(2) levels in de novo renal
      transplant patients; target levels of C(2) have been suggested. There is rare
      discussion about the C(2) target level for long-term cyclosporine-maintenance
      patients. Our objectives were to analyze the cyclosporine C(2) levels of patients
      more than 12 months after transplantation as well as changes in C(2) with time
      and the correlation between C(2) level and renal function. METHODS AND PATIENTS:
      This was a cross-sectional case-controlled study of 101 kidney recipients
      immunosuppressed with a cyclosporine-based regimen for at least 12 months. Both
      C(0) and C(2) levels were examined at various time points during outpatient
      clinic follow-up. The patients were stratified according to the time after
      transplant surgery, or to their renal function. RESULTS: The 101 patients were
      divided into three groups based on the time after renal transplant surgery.
      Groups 1, 2, and 3 represented patients transplanted for 1 to 3 years (n = 16), 4
      to 6 years (n = 35), and more than 6 years (n = 50), respectively. The C(2)
      levels for each group were 657 +/- 232, 561 +/- 186, and 580 +/- 243 ng/mL,
      respectively, (P = NS). When stratified into low versus high C(2) groups, there
      were no significant differences in renal function both at the beginning and at
      the end of 1 year follow-up. Seven of 67 patients shifted to stronger
      immunosuppression in the low C(2) group, but only 2/34 in the high C(2) group, a
      difference that was not significant (P = .234 by Fisher Exact Test). Patients
      with creatinine levels greater than 1.5 mg/dL or lower than 1.5 mg/dL showed no
      difference in C(2) on C(0) levels. Patients with deterioration of renal function
      during this period had no different C(2) levels as those with no deterioration of
      renal function. CONCLUSION: The average C(2) levels among long-term cyclosporine
      maintained patients were significantly lower than those previously suggested.
      C(2) levels did not correlate with the long-term outcome of renal function in
      patients at least 1 year after renal transplantation.

PMID- 15518763
TI  - Use of simulect can reduce the incidence of acute rejection and demonstrates with
      superior 3-year patient and graft survival rates in renal transplantation.
AB  - BACKGROUND: Acute rejection is a major cause of graft loss in renal
      transplantation. Because the highest risk for acute rejection is in the first
      month posttransplantation, improved prophylaxis could be most beneficial in this
      period. Simulect administration provides 30 to 45 days of immunoprophylaxis
      against acute rejection during the critical period after transplantation.
      OBJECTIVES: We sought to assess the incidence of acute rejection episodes and the
      safety and tolerability of Simulect plus Neoral immunosuppression. Patient and
      graft survival rates up to 3 years posttransplantation were evaluated. METHOD:
      Forty-one transplant recipients received Simulect by intravenous infusion of an
      initial 20-mg dose on the day of renal transplantation and a second 20-mg dose on
      day 4 posttransplant. All renal recipients received immunosuppression with Neoral
      and steroid. RESULTS: There were eight cases (19.5%) of acute rejection within 1
      year. The rejection episodes were easily reversed with steroid pulse therapy in
      seven patients except for graft loss. The 1-, 2-, and 3-year graft survival rates
      were 95%, 93%, and 88%, respectively. Overall, the 3-year patient survival rate
      was 100%. CONCLUSIONS: Simulect in combination with Neoral and steroid-reduced
      the incidence of acute rejection without an increase in adverse events. The low
      incidence and severity of acute rejection may have led to the superior 3-year
      patient and graft survival rates in renal transplantation.

PMID- 15518764
TI  - The role of anti-IL-2 receptor in high-risk kidney transplant patients.
AB  - Anti-IL-2 receptor has been proved to be effective in reducing the rate of acute
      rejection in kidney transplantation and also improving both the rate of graft and
      patient survival. In this study, we retrospectively review the role of anti-IL-2
      receptor as induction immunosuppression in immunologically high-risk kidney
      transplant patient compared with normally low-risk patients. METHODS: From
      January 1999 to December 2002, we performed 246 kidney transplantations in two
      transplant centers in Bangkok. These were divided into two groups: group 1, high
      risk group containing 50 patients who had one of the following criteria: (1) high
      panel reactive antibody (>50%); (2) retransplantation; (3) marginal donor (with
      expectancy of delayed graft function); (4) spouse donor; (5) >4 HLA mismatch. All
      group 1 patients receive anti-IL-2 receptor as induction immunosuppression
      (either Basiliximab (n = 27) or Daclizumab (n = 23).) Group 2 consisted of the
      control group of 196 patients with normal immunological risk. The following data
      of both groups were collected and analyzed: patient demography, type of donor,
      acute rejection incidence, severity, and time. RESULTS: In this study, the anti
      IL-2 receptors are 27 cases of Basiliximab and 23 cases of Daclizumab. The rates
      of acute rejection are not significantly different in both groups, namely, 46 of
      194 (23.7%) in group 2 compared with 10 of 50 (20%) episodes in group 1 (P =
      .602). All rejections in both groups responded to pulse steroid treatment. The
      mortality rate and rate of graft failure were also not significantly different,
      i.e., 6 of 196 (3.1%) vs 2 of 50 (4.0%) (P = .666) and 7 of 196 (3.6%) vs 3 of 50
      (6.0%) (P = .429) in low risk group versus high risk group, respectively. Kaplan
      Meier estimates of the probabilities of acute rejection free, patient survival
      rate, and graft survival rate also showed no difference between groups.
      CONCLUSIONS: The use of anti-IL-2 receptor antibodies as induction
      immunosuppression in immunologically high-risk patients results in the same rate
      of acute rejection, severity of acute rejection, graft survival, and patient
      survival as recipients with normal immunological risk.

PMID- 15518765
TI  - BK virus infection in kidney transplant recipients.
AB  - INTRODUCTION: Nephropathy associated with the polyomavirus type BK virus (BKV)
      has emerged as a cause of allograft failure linked to immunosuppressive regimens
      containing tacrolimus or mycophenolate mofetil (MMF). The outcome in BKV
      nephropathy is generally unfavorable, namely 50% of patients lose graft function.
      We herein report nine cases of BKV nephropathy after kidney transplantation.
      METHODS: From October 1998 to May 2003, 138 of 169 consecutive kidney transplant
      patients received tacrolimus-based immunosuppression, and 31 received
      cyclosporine-based immunosuppression. Additionally, 88.2% of the patients
      received mycophenolate mofetil (MMF). The diagnosis of BK infection was made by
      the presence of decoy cells in the urine and by allograft biopsy. RESULTS: There
      were nine cases of BKV nephropathy in kidney transplant recipients, an incidence
      of 5.3%. All patients with BKV nephropathy received tacrolimus, MMF, and
      steroids. The median time to diagnosis of BKV infection was 7.8 months after
      transplantation. All patients experienced an elevated serum creatinine, which
      stabilized or decreased in seven patients with altered or decreased
      immunosuppression. After a mean follow-up of 11.1 months, 2 (22.2%) of nine
      patients lost the graft. CONCLUSION: Because BKV nephropathy is a rare but
      serious complication after kidney transplantation, it should be included in the
      clinical differential of transplant dysfunction. In the absence of documented
      antiviral treatment, early diagnosis and judicious use of immunosuppressive
      agents is indicated to minimize the occurrence of BKV infection.

PMID- 15518766
TI  - Polymerase chain reaction for the diagnosis of human polyomavirus-associated
      nephropathy in renal transplant recipients.
AB  - Human polyomavirus type BK may be related to interstitial nephropathy or renal
      allograft dysfunction. Patients with nephropathy due to infection with human
      polyomavirus may be identified early using the polymerase chain reaction(PCR). We
      attempted to evaluate whether the positive response in the PCR test of BK virus
      DNA in the plasma of renal transplant recipients affects the function of the
      renal allograft. Seventy-seven patients were prospectively analyzed according to
      the operative sex, age, sources of allograft, serum creatinine levels during PCR
      test for BK virus, postoperative type of immunosuppressant, and presence of graft
      rejection. Two groups were distinguished according to the PCR result for BK
      virus: group 1 (n = 12) positive PCR reaction and group 2 (n = 65) negative
      reaction. The mean follow-up was 32.6 weeks. The incidence of positive PCR tests
      for BK virus replication after renal transplantation was 15.6%. Decoy cells in
      the urine were detected in 20.7%. The incidence of BK virus nephropathy was 1.3%.
      The mean serum creatinine levels of group 1 and 2 at the time of the PCR tests
      were 1.34 and 1.22, respectively. The rejection rates in group 1 and 2 were 8%
      and 4.5%, respectively (P > .05). We consider that a PCR assay to detect BK virus
      in renal recipients blood may be useful to identify patients at risk for
      nephropathy. It may serve as a noninvasive indicator of BK virus replication,
      although this study is limited by the short follow-up and small numbers.

PMID- 15518767
TI  - Viral infection following kidney transplantation: long-term follow-up in a single
      center.
AB  - INTRODUCTION: Viral infections are a leading cause of posttransplantation
      morbidity and mortality. The use of more potent immunosuppressive agents is
      responsible in part for the increasing incidence of some viral infections. This
      study summarized our experience with viral infections in 561 kidney transplant
      recipients. METHODS: The spectrum of viral infections in 561 consecutive kidney
      transplant recipients was examined retrospectively from November 1982 to November
      2002. RESULTS: During a mean follow-up of 64.0 months, 193 virus infections in
      156 of 561 kidney transplant recipients were recorded, an incidence of 34.2%. The
      most common viruses were cytomegalovirus (36.3%), varicella zoster virus (29.0%),
      herpes simplex virus (23.8%), BK virus (4.7%), hepatitis B virus (3.6%), and
      hepatitis C virus (2.6%). Among the CMV infections, 77.1% developed subclinical
      CMV infection and 22.9% had CMV disease. Generalized herpes zoster infection
      occurred in three cases and chicken pox in six cases. During a mean follow-up of
      64.0 months, two of 159 patients died of CMV pneumonia. CONCLUSION: Viral
      infections among the kidney transplant recipients continue to be a major problem
      despite significant progress in understanding the pathogenesis of viral infection
      and the advent of antiviral therapy.

PMID- 15518768
TI  - Therapeutic implication of quantitative pp65 antigen assay in living renal
      transplant in a high seroendemic population.
AB  - Various methods have been used to diagnose cytomegalovirus (CMV)
      infection/disease; however, pp65 antigenemia assay has emerged as a good marker
      for CMV disease in a high seroendemic population. We studied the role of
      quantitative pp65 antigen assay in live related renal transplant recipients in a
      high seroendemic population. Between November 1998 and May 2003, a total of 350
      blood samples from 250 symptomatic patients were tested by quantitative pp65
      antigen assay; 14% of the patients tested positive. There were 5 (14%) low
      positive and 30 (86%) high-positive patients. All high-positive patients had CMV
      disease. The response to antiviral therapy monitored by the assay was dramatic,
      and one low-positive patient responded to reduction in immunosuppression. In
      conclusion, pp65 antigen assay is a good test for diagnosing CMV disease and
      monitoring response to antiviral therapy in a high seroendemic population.

PMID- 15518769
TI  - Does mycophenolate mofetil increase the incidence of infections in stable renal
      transplant recipients initially treated with a two-drug regimen?
AB  - BACKGROUND: A drug regimen including a calcineurin inhibitor (cyclosporine or
      tacrolimus) and prednisone has been the mainstay of maintenance immunosuppression
      in our renal transplant recipients for more than 10 years. After the introduction
      of mycophenolate mofetil (MMF), a new, potent immunosuppressant that may reduce
      the incidence of late rejection in renal transplant recipients, the
      immunosuppressive protocol in some recipients was changed to an MMF-based
      regimen. We sought to ascertain whether the addition of MMF lead to greater
      susceptibility to infectious complications. PATIENTS AND METHODS: Between May
      1991 and November 2002, all renal transplant recipients who received a two-drug
      regimen initially for more than 6 months were changed to an MMF-based regimen.
      The study includes patients with functional grafts for more than 6 months
      thereafter. Differences in the incidence, etiology, and outcome of infections
      were compared during the non-MMF versus the MMF periods. RESULTS: Eighty patients
      of mean age of 38.6 years (range 13 to 69) included 43 men and 37 women. The mean
      daily MMF dose was 663 mg/patient (range 250 to 1500 mg). The mean follow-up time
      of non-MMF period and MMF periods were 3.4 and 2.1 years, respectively. The
      overall incidence of infections in the two periods was similar (0.2
      infections/patient in the non-MMF period and 0.25 infections/patient in the MMF
      period, P = .57). No mortality was associated with these infectious
      complications. In conclusion, addition of MMF, a more potent immunosuppressive
      protocol, did not increase the incidence of infections in stable renal transplant
      recipients initially treated with a two-drug regimen.

PMID- 15518770
TI  - Antiviral therapy for hepatitis B after kidney transplantation.
AB  - The clinical outcome of HBsAg-positive renal transplant recipients has been
      adversely affected by potentially fatal acute hepatitic exacerbations and chronic
      liver disease, in addition to the increased risk of hepatocellular carcinoma. The
      difficulty in predicting the evolution and severity of liver disease after kidney
      transplantation further confounds the management of these patients. The clinical
      course of HBsAg-positive renal transplant recipients can be modified favorably
      after nucleoside analogue therapy and quantitative HBV DNA assays have become
      available. The latter allow earlier detection of increased viral replication,
      before the onset of biochemical abnormality. We have combined serial HBV DNA
      monitoring with preemptive lamivudine therapy, and our results showed that this
      strategy markedly improved patient survival. Prolonged treatment, however, was
      associated with the selection of drug-resistant YMDD variants. Hepatitic flares
      were common after the development of drug resistance and could lead to
      decompensation in a small proportion of patients. With careful selection,
      discontinuation of antiviral treatment was feasible in 18.5% of treated subjects.
      While the outcome of HBsAg-positive renal allograft recipients should continue to
      improve with the availability of more effective antiviral agents, financial
      constraints and the paucity of research data could hamper the optimal adoption of
      recent advances into clinical practice.

PMID- 15518771
TI  - A survey on the prevalence and management of hepatitis B after renal
      transplantation in Asian-Pacific countries.
AB  - The carrier rate for hepatitis B virus (HBV) varies from 1% to 2% to 10% in Asian
      Pacific countries. A survey involving 12 transplant centers from 11 countries in
      this region showed that 1% to 25% of kidney transplant recipients were infected
      with HBV, and up to 60% of these subjects showed abnormal liver biochemistry.
      While nearly all centers tested anti-HBs in potential kidney transplant
      recipients, HBV vaccination of nonimmune subjects was routine in only 66.7%. One
      third of the surveyed units rejected HBsAg-positive subjects as kidney donors,
      while the others demonstrated differing policies in choosing the respective
      recipients. Two units (16.7%) excluded HBsAg-positive patients from kidney
      transplantation, whereas the others only excluded those with severe liver
      disease. Heterogeneity also applies to the immunosuppressive regimens, the use of
      HBV DNA in serial monitoring, and the timing of antiviral therapy in HBsAg
      positive kidney transplant recipients. The data showed that despite HBV infection
      being a significant problem in kidney transplantation, there is a lack of uniform
      management policy, attributable to the clinical complexity and deficiency of
      research data. Although improvement in clinical outcome is likely with the advent
      of nucleoside analogue therapy and better monitoring, the financial implications
      in the adoption of these recent advances remain realistic concerns.

PMID- 15518772
TI  - Intestinal cryptosporidiasis in living related renal transplant recipients.
AB  - Cryptosporidium infestations are common in immunocompromised AIDS patients.
      However, the literature in renal transplant recipients is scarce. We conducted a
      study to know the prevalence, disease manifestations, and management of
      cryptosporidial infestations in live related renal transplant recipients.
      Cryptosporidial infestations were observed in 20% of patients, including 16.6%
      who had symptomatic diarrhea. We conclude that the prevalence is high in the
      transplant population, but only a few patients are symptomatic. Clinicians should
      routinely request special stains to demonstrate cryptosporidium in stool
      specimens.

PMID- 15518773
TI  - Effect of tacrolimus and cyclosporine on renal microcirculation and nitric oxide
      production.
AB  - OBJECTIVES: Cyclosporine (CSA) and tacrolimus (TAC) frequently induce
      nephrotoxicity and similar pathologic changes. Acute CSA-induced nephrotoxicity
      has been reported to be mediated by activation of vasoconstrictors such as
      endothelin. The purpose of the present study was to investigate the acute effects
      of TAC and CSA on the renal microcirculation and upon a vasodilator such as
      nitric oxide (NO) production. METHODS: Renal blood flow (RBF) in the
      microcirculation was measured by a Laser Doppler flow meter in uninephrectomised
      rats. RBF, mean arterial pressure (MAP), and renal vascular resistance (RVR) were
      measured in the following groups: (a) TAC (0.1 to 2.0 mg/kg/h, n = 3
      approximately 6); CSA (20 and 50 mg/kg/h, n = 5); (b) L-NAME (10 mg/kg), an NO
      synthase inhibitor, 8 minutes prior to TAC (0.5 and 1.5 mg/kg/h, n = 5), or CSA
      (20 and 50 mg/kg/h, n = 5). Stable NO end-products, serum NO(2) and NO(3), were
      measured by the Griess method (n = 5). RESULTS: None of the parameters were
      changed by TAC alone, whereas TAC with L-NAME significantly reduced RBF (-28 +/-
      7%) and increased RVR (46 +/- 17%) in a dose-dependent manner. CSA alone
      significantly reduced RBF (-37 +/- 6%) and increased RVR (69 +/- 22%) without any
      changes in MAP. The effects of CSA were enhanced by L-NAME. Serum concentration
      of NO(2) + NO(3) was significantly reduced by both L-NAME alone and CSA (50
      mg/kg) (P < .05), while there were no changes with TAC (1.5 mg/kg). CONCLUSIONS:
      Blockade of NO production enhance the vasoconstrictive effect of CSA, and
      unmasked such an effect of TAC. These results suggest that the nephrotoxicity of
      CSA and TAC may involve the NO system.

PMID- 15518774
TI  - Effect of epigallocatechin gallate on renal function in cyclosporine-induced
      nephrotoxicity.
AB  - INTRODUCTION: Nephrotoxicity is a clinically important side effect of
      cyclosporine (CsA). CsA-induced nephrotoxicity results from increased production
      of free radical species in the kidney. Epigallocatechin gallate (EGCG) acts as an
      antioxidant, thus, EGCG may have a protective effect on the alteration of renal
      function resultant from oxygen free radicals. The purpose of the present study
      was to investigate the protective effect of EGCG in a rodent model. METHODS:
      Experiments were performed on 3 groups. The normal control group (group 1)
      received normal saline solution. The CsA-treated group (group 2; 15 mg/kg body
      weight/d for 14 days) received subcutaneous injections. The EGCG-treated group
      (group 3) in addition received 25 mg of EGCG/kg body weight by intraperitoneal
      injection. RESULTS: There were significant increases in levels of blood urea
      nitrogen (BUN)(42.8 +/- 8.2 mg/dL; P < .001), serum creatinine (1.18 +/- 0.60
      mg/dL; P < .05), and serum malondialdehyde (3.09 +/- 0.20 nmol/mL; P < .001), and
      a significant decrease in CCr(0.07 +/- 0.02 mL/min; P < .001) in group 2 compared
      with group 1. Levels of BUN (30.2 +/- 0.7 mg/dL; P < .01)and CCr (0.12 +/- 0.08
      mL/min) were lower in group 3 than in group 2. Serum creatinine (0.71 +/- 0.04
      mg/dL) and serum malondialdehyde level (2.13 +/- 0.15; P < .001 nmol/mL) were
      lower in group 3 than in group 2. There was no significant difference in CsA
      levels between group 2 (6.86 +/- 1.48 mug/mL) and group 3 (6.69 +/- 0.62 mug/mL).
      CONCLUSIONS: EGCG treatment significantly protected renal function and free
      radical-mediated injury in the kidney from CsA-induced changes.

PMID- 15518775
TI  - Microscopic examination of the urine helps to confirm the recovery of acute
      tubular necrosis after cadaveric renal transplantation: a case report.
AB  - INTRODUCTION: Delayed graft function due to acute tubular necrosis (ATN) is
      frequently seen in kidney transplants from non-heart-beating donors. However,
      only a biopsy can be used to assess the severity of ATN. Therefore, we studied
      the validity of microscopic findings in tubular epithelial cells (TECs) from
      urine as a means to monitor ATN. MATERIALS AND METHODS: The first voided urine in
      the morning was examined for the appearance and nuclear cytoplasmic (N/C) ratio
      of the TECs, using a murine staining with URO-3 monoclonal antibody to detect
      proximal tubular cells (PTCs). CASE: A 58-year-old man underwent cadaveric kidney
      transplantation in January, 2003 using tacrolimus, mycophenolate mofetil, and
      prednisone following basiliximab induction therapy. His graft did not function
      immediately; needle biopsy was performed on day 17. The pathological findings
      showed severe ATN without evidence of acute rejection. A large quantity of TECs
      was seen in his urine between days 7 and 14. After day 28, TECs with a large N/C
      ratio and that were URO-3 antibody-positive were detected. Urine volume increased
      gradually and hemodialysis was not necessary after day 36. CONCLUSION: The
      presence of URO-3-positive TECs with large N/C ratios suggests the reconstruction
      of PTCs. Therefore, it may be useful to monitor TEC findings to assess the
      severity ATN after cadaveric kidney transplantation.

PMID- 15518776
TI  - Risk factors and incidence of posttransplant diabetes mellitus in renal
      transplant recipients.
AB  - OBJECTIVE: This study reviewed the incidence of post-transplantation diabetes
      mellitus (PTDM) and risk factors for its development among renal transplant
      recipients in Malaysia. METHODS: Records of all kidney recipients with no known
      diabetes mellitus prior to transplantation and followed for at least 6 months
      posttransplant were selected for this retrospective study. PTDM was diagnosed
      according to American Diabetic Association/WHO criteria or the need to start
      insulin or an oral hypoglycemic agent. The data set included recipient age,
      gender, race, weight, donor type, duration of transplant, HCV antibody status,
      and immunosuppressive medication. RESULTS: Of the 316 patients who fulfilled the
      selection criteria, 13.3% had PTDM. Gender, race, type of donor, HCV serologic
      status, and use of tacrolimus did not differ significantly between recipients
      with versus without PTDM. However, recipients who developed PTDM were
      significantly older (median age 50.5 versus 42.0 years, P < 0.0001), had
      significantly longer posttransplant follow-up (median duration 125.5 versus 85.0
      months, P = .0030) and weighed more at transplantation/first follow-up (median
      weight 57.6 versus 52.3 kg, P = .0103). CONCLUSION: The overall cumulative
      incidence of PTDM in this study was similar to the published reports. Older age,
      longer posttransplant duration, and heavier weight were the only variables
      significantly associated with PTDM.

PMID- 15518777
TI  - Impact of fluvastatin on hyperlipidemia after renal transplantation.
AB  - BACKGROUND: Renal transplant recipients are at increased risk of atherosclerotic
      vascular disease with hyperlipidemia. Many recipients have preexisting
      cardiovascular disease at the time of transplantation, and immunosuppressive
      therapy may aggravate existing risk factors or promote development of new risk
      factors, notably hyperlipidemia and hypertension. Fluvastatin is one of the
      statins, an HMG-CoA reductase inhibitor, which has been shown to be effective in
      lowering cholesterol levels. We treated hyperlipidemia after renal
      transplantation with Fluvastatin for more than 6 months. We attempted to clarify
      the efficacy of fluvastatin on hyperlipidemia in renal transplant recipients.
      MATERIALS: Forty-five renal transplant recipients with hyperlipidemia were
      enrolled in this study. The mean age was 44.2 years, with 23 men and 22 women.
      Thirty-seven transplantations were from a living related donors and eight from
      cadaveric donors. Thirty-three recipients were ABO-compatible, seven recipients
      had minor mismatches, and five recipients were ABO-incompatible. The dose of
      fluvastatin was 20 mg per day. Levels of total cholesterol (TC), triglyceride
      (TG), HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), serum creatinine (s-Cr),
      ALT, ALP, uric acid (UA), hematocrit (Ht), CPK, and blood pressure were examined
      in all recipients before treatment as well as 1, 3, and 6 months after
      Fluvastatin administration. RESULTS: The mean levels of TC and TG were
      significantly reduced from 256, to 224 and 215 mg/dL, and from 188 to 170 and 147
      mg/dL at 1 and 6 months after treatment, respectively. The mean levels of HDL-C
      were 72 mg/dL before treatment, 81 mg/dL at 1 month, and 80 mg/dL at 6 months
      after treatment. The mean levels of LDL-C were 153 mg/dL before treatment, 145
      mg/dL at 1 month, and 145 mg/dL at 6 months after treatment. Fluvastatin
      significantly produced a reduction rate in TC of 16%, TG of 22%, and LDL-C of 5%
      after 6 months of treatment, respectively. The mean levels of HDL-C of were
      increased 10% after 6 months of treatment. The serum creatinine and CPK were not
      significantly different. There were no clinically significant differences in
      other factors. No significant adverse effects were observed. CONCLUSIONS:
      Fluvastatin seemed to be safe and highly effective to control TC, TG, LDL-C, and
      HDL-C in renal transplant recipients.

PMID- 15518778
TI  - Posttransplant Kaposi's sarcoma: report from a single center.
AB  - Posttransplant Kaposi's sarcoma (KS) is not uncommon. This study investigated the
      clinical manifestations, impact of immunosuppression, and presence of HHV-8
      antigen in our patients. METHODS: Among 568 renal transplant recipients, four
      developed KS. The physical findings, radiologic studies, immunosuppressive
      regimens, and the clinical outcomes were reviewed. In two patients, the
      expression of human herpes virus-8 was examined with polymerase chain reaction
      and in situ hybridization. RESULTS: The incidence of KS was 0.7% in our
      recipients. The intervals between the transplantation and the development of KS
      ranged from 2 months to 8.4 years. All KS patients had calcineurin inhibitor
      based antirejection therapies. Peripheral lymphadenopathy was the initial
      manifestation in three of four patients; the fourth presented with violaceous
      papules over his lower legs. Besides lymphadenopathy, KS in one patient also
      involved internal visceral organs. One patient died at the time of diagnosis
      because of Salmonellosis; the other three experienced tumor regression after
      discontinuation of calcineurin inhibitors. HHV-8 expression was detected in two
      examined specimens. CONCLUSION: Lymph node involvement is the most common
      clinical presentation in our posttransplant KS patients. HHV-8 infection is
      associated with the development of KS. Early withdrawal of calcineurin inhibitors
      produces a favorable outcome in posttransplant KS.

PMID- 15518779
TI  - Posttransplant lymphoproliferative disease masquerading as postbiopsy hematoma.

PMID- 15518780
TI  - De novo cancer occurrence after renal transplantation: a medical center
      experience in Taiwan.
AB  - INTRODUCTION: Renal transplantation has been advocated as the treatment of choice
      for end-stage renal disease. Organ transplantation increases the incidence of
      cancer through unclear mechanisms. A literature review showed that the most
      common neoplasms are of skin origin, which are uncommon in Eastern people. We
      reviewed cancer patterns in our renal transplant series. MATERIALS AND METHODS:
      From July 1981 to December 2002, among 560 renal transplantations performed in
      this hospital, we retrospectively surveyed cancer incidence, types, and usage of
      immunosuppressants. RESULTS: Twenty nine cancer cases 5.18% (incidence) included
      hepatocellular carcinoma (HCC) as the highest mortality rate (9 of 13 cases).
      Eight of these 13 cases were hepatitis B carriers. All four hepatitis C carriers
      expired three of them with unresectable multinodular tumors at diagnosis in
      Posttransplantation lymphoproliferative disorder (PTLD) was the second most
      common cancer (seven cases); all but one survived with reduced doses of or
      changes in immunosuppressants. No skin cancer other than four Kaposi's sarcomas
      with skin manifestations was detected in our series. DISCUSSIONS: HCC was the
      main cancer in our series. Accepting hepatitis B carriers as candidates for renal
      recipients and donors may be one of the causes. PTLD was the second most common
      cancer, while there were no skin cancers.

PMID- 15518781
TI  - Transitional cell carcinoma in renal transplant recipients.
AB  - We describe our experience in managing transitional cell carcinoma (TCC) in renal
      transplant (RTx) recipients. Nineteen RTx recipients (7 men; 12 women) presented
      with hematuria or hydronephrosis of native kidneys and were suspected with TCC
      were reviewed retrospectively; 17 of them proved to have TCC. The mean interval
      of the occurrence of TCC was 58.7 months (range, 3-144 months) after RTx. The
      patients with suspected upper tract lesions received bilateral
      nephroureterectomies (BNU) and bladder cuff resection. Transurethral resection of
      the bladder tumor (TUR-BT) was performed in patients with concomitant or solitary
      superficial bladder lesions. Of the 15 patients with upper tract TCC, 8 had
      bilateral lesions pathologically, but only 2 of them were suspected
      preoperatively on image study. With a mean follow-up of 28 months (range, 1-57
      months) both the overall graft and patient survival rates were 76%; 4 patients
      with advanced diseases at presentation died. Bladder recurrence was noted in 6
      patients (35%). Transplant patients with hematuria warrant detailed study of the
      whole urinary system and periodic ultrasonography of the native kidneys is
      recommended in all RTx recipients. Simultaneous BNU for the native kidneys is
      mandatory if there is any evidence of TCC in either renal/ureteral unit.

PMID- 15518782
TI  - A case of fungal sepsis due to aspergillus spondylitis followed by
      cytomegalovirus infection in a renal transplant recipient.
AB  - Although advances in immunosuppressive therapy have led to increased survival of
      renal transplant recipients, there are greater risks of developing infectious
      complications. Because of its rarity and the lack of medical awareness,
      aspergillus spondylitis is often misdiagnosed as tuberculous spondylitis,
      especially in its early stages. We report a case of aspergillus spondylitis in a
      renal transplant followed by cytomegalovirus (CMV) retinitis. CASE: A 59-year-old
      woman was admitted due to general weakness and abdominal discomfort. She had
      undergone renal transplantation 3 years previously. One month before admission,
      she was diagnosed with CMV retinitis and treated with IV ganciclovir. On
      admission, she suffered from lower abdominal pain. Colonoscopy revealed multiple
      circular or patchy ulcers with surrounding severe mucosal edema in the sigmoid
      colon findings consistent with intestinal tuberculosis. On hospital day 30, she
      complained of lower extremity paresthesia and weakness. An MRI of the spine
      revealed a well-demarcated paraspinal mass around the L2-4 body; tuberculous
      spondylitis was initially considered. But despite antituberculosis medication,
      the patient progressed to spastic paraparesis and sensory changes in both lower
      legs, requiring urgent surgical decompression. At hospital day 60, she suffered
      persistent fever and developed thrombocytopenia. Wound discharge continued and
      paraparesis became denser. A CT of the spine showed progression of the paraspinal
      abscess from the L2 body to the iliac crest. CT-guided psoas muscle drainage was
      performed. Fungal culture showed Aspergillus species. Despite antifungal therapy,
      the patient died after a prolonged hospital stay due to fungal sepsis and septic
      shock from aspergillosis.

PMID- 15518783
TI  - A case of primary cutaneous aspergillosis in a renal transplant recipient.
AB  - Opportunistic fungal infections are life-threatening complications which are a
      major cause of morbidity and mortality in immunocompromized hosts such as those
      who have undergone organ transplantation. Aspergillosis comprises a spectrum of
      disease caused by a ubiquitous saprophytic mold. Invasive aspergillus is a
      serious life-threatening complication in immunocompromised hosts. Primary
      cutaneous aspergillosis occurs relatively less frequently and is poorly
      characterized. We report a case of cutaneous aspergillosis in a 51-year-old renal
      transplant recipient, which was successfully treated with local excision and
      concomitant antifungal therapy. CASE: A 51-year-old male renal transplant
      recipient presented with cutaneous nodules on the dorsum of the right hand. He
      underwent renal transplantation for end-stage renal disease due to adult dominant
      polycystic kidney disease (ADPKD) 3 years prior. Initially he suffered an acute
      rejection episode that was treated with steroid pulse and OKT3 therapy.
      Eventually he was stabilized on a combination of tacrolimus, prednisone, and
      mycophenolate mofetil. Three years after transplantation, he developed painless
      multiple (largest one 5 x 3 cm sized) nodules on the dorsum of his right hand. He
      was afebrile with no systemic symptoms. A skin biopsy showed a dense solid
      infiltration of giant cells, histiocytes, and lymphoplasma cells admixed with
      intra- and extracellular fungal hyphae and spores. The hyphae were septate and
      acute angle branching, which was consistent with aspergillosis. Oral itraconazole
      200 mg/d for 5 weeks was ineffective. Treatment with liposomal amphotericin B for
      4 weeks was initiated and MMF was discontinued. The medication was well tolerated
      with no hepatotoxic effects. Although new lesions did not appear, existing ones
      did not significantly improve after 4 weeks of treatment. Therefore, most lesions
      were excised surgically and liposomal amphotericin B continued for 2 weeks
      followed by treatment with oral fluconazole for 2 months. Ten moths later there
      was no evidence of recurrence.

PMID- 15518784
TI  - Postoperative alopecia areata: is pressure-induced ischemia the only cause to
      blame?
AB  - INTRODUCTION: Postoperative alopecia areata (PAA) following surgery has been
      reported, especially after certain gynecologic and cardiac procedures; however,
      no cases have been reported after liver transplant (LT). Localized pressure
      associated with prolonged anesthesia is usually blamed. Herein we report a few
      cases of PAA encountered especially in relation to LT procedures. OBJECTIVE: To
      report our PAA cases, identifying possible contributing risk factors. METHODS:
      Between April 2001 and May 2003 the data on eight PAA cases were analyzed for
      age, sex, type of surgery, duration of anesthesia, type of head support, periods
      of hypotension, and psychiatric comorbidity. RESULTS: Median age of affected
      patients was 27 years (10 to 44) and the male/female ratio 3/5. The type of
      surgery included: two LT recipients, two LT donors, three cardiac valve
      replacements, and one coronary bypass surgery. Median anesthesia time was 6 hours
      (3 to 12). Sponge or jelly donut was used for head support with frequent change
      of its position as per protocol. There were no significant periods of
      hypotension. Surprisingly, almost all patients had a documented psychiatric
      comorbidity, mainly anxiety, adjustment/adaptation, or mood disorders.
      CONCLUSIONS: PAA is a rare complication following certain surgeries including
      both donor and recipient LT procedures. Although pressure-induced ischemia is the
      most likely etiological factor, we believe that psychiatric comorbidity plays a
      major role in its development. Therefore, preoperative thorough psychiatric
      counseling in addition to frequent intraoperative head repositioning will help to
      avoid this minor but distressing postoperative complication.

PMID- 15518785
TI  - Two cases of recurrent IgA nephropathy following kidney transplantation.
AB  - Recurrence of immunoglobulin (Ig) A nephropathy following kidney transplantation
      has been described as occurring in 40% to 60% of cases. Although this type of
      recurrence was considered a benign condition for a long time, more recent data
      showed that recurrent transplant IgA nephropathy may be a significant contributor
      to graft loss. We present 2 cases of recurrent IgA nephropathy following kidney
      transplantation. In case 1, renal function remained stable with a creatinine
      level of 1.2 mg/dL at 5 months after diagnosis and 61 months after
      transplantation. In case 2, the patient lost his graft and returned to regular
      hemodialysis at 36 months after diagnosis and 125 months after kidney
      transplantation.

PMID- 15518786
TI  - Mucocutaneous lesions in transplant recipient in a tropical country.
AB  - Dermatological manifestations are common in renal transplant patients, but differ
      markedly with ethnic group and geographical location. We studied mucocutaneous
      lesions in 54 renal allograft recipients (related donors = 30; unrelated donors =
      24) living in tropical atmospheres. Their gender was 50 males, and 4 females
      ranging in age between 15 and 63 years (mean = 37.84 years). The mean duration of
      follow-up was 124 months (range = 4 to 173 months). All patients received kidneys
      from living donors and were kept on immunosupression with mean daily doses of
      prednisolone, azathioprine, and cyclosporine of 10.2 mg, 68.6 mg, and 252 mg,
      respectively. The mean trough concentration of cyclosporine was 185 ng/mL. The
      mucocutaneous lesions were divided into four groups: drug-induced (n = 24,
      44.4%), fungal (n = 18, 33.3%), viral (n = 9, 16.6%), and bacterial (n = 10,
      18.5%). Cushingoid features, gum hypertrophy, and hypertrichosis were seen in 7
      (12.9%) patients. Steroid acne was seen in three cases. Pityriasis versicolor was
      the most common (20.3%) fungal infection of the skin. In addition, Tinea unguium
      and mucocutaneous candidiasis were noted in four and three cases respectively.
      Herpes virus infection (Herpes zoster 5; Herpes simplex 2) was noted in 7 (12.9%)
      cases. Chicken pox at 5 years posttransplant and cutaneous vasculitis associated
      with cytomegalovirus disease at 6 months posttransplant were seen in one case
      each. We have not seen warts in our patients. Pyogenic bacterial infection of
      skin in the form of abscess (n = 6), cellulitis (n = 3), and pyoderma (n = 1)
      were observed in 10 (18.5%) patients. Thus, drug-induced mucocutaneous side
      effects and skin fungal infections are the most common dermatological
      manifestations among renal transplant recipients living in a tropical country.

PMID- 15518787
TI  - Effect of melatonin on the malondialdehyde level of neutrophils in cyclosporine
      treated rats.
AB  - INTRODUCTION: Cyclosporine (CsA) may contribute to oxygen free radical metabolism
      in neutrophils, thus resulting in the damage to these cells. This damage may be
      mitigated by antioxidants such as melatonin. In this study, we measured the
      malondialdehyde level, which was used as a marker of free radical-induced tissue
      damage from neutrophils in rats treated with CsA and melatonin. METHODS: The
      experiments included the following: (1) normal controls (group 1) that received
      Cremophor EL and 0.5 mL of 5% ethanol-saline solution; (2) CsA alone-treated
      (group 2) rats that received 15 mg/kg of body weight per day for 14 days by
      subcutaneous injection; and (3) melatonin-treated (group 3) rats received CsA as
      for group 2 plus melatonin (715 mug). RESULTS: Malondialdehyde level was
      significantly higher among group 2 (13.34 +/- 7.54 nmol/10(7) neutrophils) than
      group 1 animals (7.33 +/- 2.63 nmol/10(7) neutrophils; P < .05). The level was
      significantly lower in group 3 (5.58 +/- 1.59 nmol/10(7) neutrophils) than group
      2 (P < .01). CsA levels were not significantly different between group 2 (6.25 +/
      1.60 mug/mL) and group 3 (6.09 +/- 2.01 mug/mL). CONCLUSIONS: In this
      experiment, the malondialdehyde level in neutrophils was increased after CsA
      treatment, suggesting that damage resulted from oxygen free radicals by CsA. This
      damage was reduced by melatonin. Thus, CsA-induced neutrophils oxidative damage
      may be protected by melatonin in transplant recipients.

PMID- 15518788
TI  - Recurrence of focal glomerulosclerosis in post-renal transplant recipients:
      report of two cases.
AB  - INTRODUCTION: Focal segmental glomerulosclerosis (FGS) has a tendency to recur
      frequently after kidney transplantation. To evaluate the incidence and outcome of
      recurrence of FGS, we report 2 cases of recurrence. PATIENTS: Among 12 patients
      with renal failure caused by biopsy-proved FGS who received kidney allografts
      from living related donors, 2 experienced recurrent FGS. CASE REPORTS: Case 1 was
      a 28-year-old man who received a renal transplant from his mother. The recurrence
      of FGS happened just after the scheduled reduction in immunosuppressants at 36
      months after the transplantation. He developed subsequently end-stage renal
      failure (ESRD) 50 months after transplantation. Case 2 was a 22-year-old man who
      received a renal transplant from this ABO disparate mother. A few days after
      renal transplantation, he displayed a severe nephrotic syndrome due to recurrent
      FGS, reaching ESRD at 23 months. To treat recurrent FGS, plasma exchange was
      partially effective, reducing the proteinuria but not stopping the progression of
      disease. DISCUSSION: Two recipients with severe proteinuria were diagnosed as
      having recurrent FGS. The incidence of recurrent FGS was 16.7% with 5-year and 10
      year graft survival rates among recipients with ESRD caused by FGS of 79.6% and
      68.2%, respectively. The incidence and graft survival rates were better than
      those expected based upon previous reports. Once the recurrence occurred, it was
      difficult to halt the progression of disease. Effective prevention of FGS and
      careful observations with maintained of immunosuppression are necessary in these
      patients.

PMID- 15518790
TI  - Impact of HLA-identity on results of ABO-incompatible living kidney
      transplantation.
AB  - INTRODUCTION: Due to the continuing shortage of cadaveric donors in Japan, ABO
      incompatible living kidney transplantation is being performed. Our previous
      studies showed that the long-term graft survival in ABO-incompatible living
      kidney transplantation was comparable to that in ABO-compatible living kidney
      transplantation. However, the impact on HLA-identity on the results of ABO
      incompatible living donor kidney transplantation had not been investigated
      previously. MATERIALS AND METHODS: One hundred twenty-seven recipients underwent
      ABO-incompatible living kidney transplantation between January 1989 and December
      2000. Five were grafted from HLA-identical sibling donors group (I). The
      remaining 122 recipients received grafts from an HLA-nonidentical donor (group
      N). Both groups were similar in terms of recipient age, donor age, warm ischemic
      time, and total ischemic time. Three or four sessions of plasmapheresis were
      performed prior to transplantation. Cyclosporine or tacrolimus,
      methylprednisolone, and azathioprine or mycophenolate mofetil were used for
      immunosuppression. Splenectomy was done at the time of kidney transplantation in
      all patients. RESULTS: Graft loss was seen in one of the five HLA-identical
      recipients due to chronic rejection. Five- and 10-year graft survival rates were
      80.0% I vs 72.0% N, and 80.0% I vs 54.2% N, respectively. The incidence of acute
      rejection in the HLA-identical recipients was lower than that in the HLA
      nonidentical recipients (20% I vs 67.2% N). In conclusion, long term graft
      survival among ABO-incompatible kidney transplants from HLA-identical sibling
      donors was much better than that from HLA-nonidentical sibling donors.

PMID- 15518789
TI  - Impact of positive PRA on the results of ABO-incompatible kidney transplantation.
AB  - INTRODUCTION: Due to the continuing shortage of cadaveric donors in Japan, ABO
      incompatible living kidney transplantation (LKT) is being performed. It is well
      known that highly sensitized patients with positive panel reactive antibodies
      (PRA) often present with acute rejection. Therefore, we examined the impact of a
      positive PRA on the results of ABO-incompatible LKT. MATERIALS AND METHODS: One
      hundred seventy-seven recipients underwent ABO-incompatible LKT between January
      1989 and March 2003. Of these patients, 37 who had been examined for PRA before
      transplantation were included in this study. There were 25 men and 12 women of
      mean age 37.3 years. Plasmapheresis was performed to remove anti-ABO antibodies
      before transplantation. During the induction phase, methylprednisolone,
      azathioprine, or mycophenolate mofetil and cyclosporine or tacrolimus were used
      for immunosuppression. Splenectomy was performed at the time of kidney
      transplantation in all patients. PRA was measured using FlowPRA by flow
      cytometer. RESULTS: Eight of the 37 patients had a positive PRA before
      transplantation (class I, 5; class II, 1; class I and class II, 2). The incidence
      of acute rejection was 37.9% in the patients with a negative PRA and 37.5% in
      patients with a positive PRA. One patient with a negative PRA and one patient
      with a positive PRA lost grafts due to acute rejection. CONCLUSIONS: Positive PRA
      may not increase the incidence of acute rejection in ABO-incompatible LKT because
      plasmapheresis and splenectomy are performed to eliminate anti-ABO antibody.

PMID- 15518791
TI  - Excellent outcome of ABO-incompatible living kidney transplantation under
      pretransplantation immunosuppression with tacrolimus, mycophenolate mofetil, and
      steroid.
AB  - INTRODUCTION: ABO-incompatible living kidney transplantation (LKT) has been
      performed to widen the indications for kidney transplantation. Since 2001, using
      a 7-day period of pretransplantation immunosuppression with tacrolimus (FK) plus
      mycophenolate mofetil (MMF) plus methylprednisolone (MP), we have observed a
      marked reduction in acute humoral/vascular rejection without any serious
      complications. PATIENTS AND METHODS: Forty-five adult patients underwent ABO
      incompatible LKT at our institute between January 2000 and September 2002. There
      were 20 men and 25 women of mean age 33 years. Plasmapheresis was performed to
      remove anti-AB antibodies prior to kidney transplantation. In 2000, 13 patients
      were treated with FK plus MMF plus MP without 7-day pretransplantation
      immunosuppression (group 1). Since January 2001, we have administered FK (0.1
      mg/kg/d) plus MMF (1-2 g/d) plus MP (125 mg/d) concomitantly with plasmapheresis
      starting from 7 days before transplantation in 32 patients (group 2). Splenectomy
      was performed at the time of kidney transplantation in all patients. RESULTS:
      Patient survival rate was 100% in both treatment groups. Graft survival rate was
      92% and 97% in groups 1 and 2, respectively. One patient in group 1 lost the
      graft due to severe pancreatitis and 1 patient in group 2, due to severe humoral
      rejection. The incidence of acute rejection was 56% and 19% in group 1 and group
      2, respectively. No patient experienced any lethal infectious complication.
      CONCLUSION: Pretransplantation immunosuppression for 7 days using FK, MMF, and MP
      in ABO-incompatible LKT provides an excellent outcome without severe infectious
      complications.

PMID- 15518792
TI  - Efficacy of IgM anti-blood type antibody monitoring by enzyme-linked
      immunosorbent assay after renal transplantation across the blood barrier: high
      dose immunoglobulin administration blocks IgM rather than IgG anti-blood type
      antibodies.
AB  - We used an enzyme linked immunosorbent assay (ELISA) to investigate the presence
      of subtypes of anti-blood-type antibodies in patients with biopsy-proven humoral
      rejection after ABO-incompatible renal transplantation. High agglutinin IgG and
      IgM anti-blood type antibodies from 12 ABO-incompatible recipients with vascular
      rejection were separately assessed using an ELISA. Patients who exhibited
      excellent renal function despite high agglutinin titers of anti-blood-type
      antibodies(n = 8) were also examined. All 12 rejection patients exhibited highly
      elevated titers of IgG and IgM, while the eight stable patients exhibited only
      slightly elevated IgG titers, but not IgM. IgG and IgM titers did not change
      after plasmapheresis and steroid pulse therapy, whereas IVIg treatment
      significantly blocked both IgG and IgM, with IgM being blocked to a larger extent
      than IgG. Blocking of IgM seems to play an important role in improving ABO
      incompatible grafts.

PMID- 15518793
TI  - Efficacy of basiliximab induction therapy in ABO-incompatible kidney
      transplantation: a rapid steroid withdrawal protocol.
AB  - INTRODUCTION: We have performed ABO-incompatible (ABO-i) kidney transplantation
      (KT) to alleviate the severe organ shortage in our country. Induction therapy
      with basiliximab, a monoclonal anti-interleukin-2 receptor antibody, is known to
      be effective in reducing the incidence of acute rejection (AR) after ABO
      compatible KT. However, the efficacy of basiliximab in ABO-i KT is still unknown.
      In this study, we evaluated the effect of basiliximab to decrease overall
      maintenance immunosuppression (a steroid withdrawal protocol) and to improve the
      outcome of ABO-i KT. PATIENTS AND METHODS: Between April 2002 and May 2003, 14
      adult patients underwent ABO-i KT from living donors with cyclosporine (CsA)
      based immunosuppression. There were seven men and seven women of mean age 48 +/-
      10 years. Three of the 12 cases were second KT. Three sessions of plasmapheresis
      were performed to remove anti-AB antibodies before KT. Splenectomy was performed
      in all patients. Immunosuppression consisted of methylprednisolone (MP), CsA, and
      mycophenolate mofetil, in addition to antibody induction with basiliximab. MP was
      completely withdrawn on postoperative day 14. RESULTS: In 3 of 14 recipients, MP
      was restarted because of AR or a suspicion of AR. Both patient and graft
      survivals were 100%. The incidence of biopsy-proven AR was 14% (2/14). There was
      no adverse effect related to the antibody therapy. CONCLUSION: The use of
      basiliximab induction therapy may eliminate the need for steroid maintenance
      therapy without increasing AR risk, even among ABO-i KT recipients. We conclude
      that basiliximab provides safe and effective induction immunosuppression in ABO-i
      KT recipients.

PMID- 15518794
TI  - The utility of resistance index of distal interlobular arteries in evaluating
      renal graft function.
AB  - The correlations of the mean values of resistance index (RI) of the distal
      interlobular, arcuate, and interlobal arteries of the kidneys were evaluated with
      HDI 5000 ultrasonographic system using a 2- to 5-mHz scan probe under the power
      Doppler detection mode in 60 patients with various native renal conditions and 70
      renal allografts. The mean values of RIs of the distal interlobular arteries and
      those of the interlobal arteries in the renal allografts were significantly
      correlated with the recipients' renal functions (P = .015 and .030,
      respectively), whereas those of arcuate arteries were not.

PMID- 15518795
TI  - Body composition by bioelectrical impedance analysis in renal transplant
      recipients.
AB  - Bioelectrical impedance analysis was introduced more than a decade ago to measure
      body composition and nutritional status. There are presently limited data on the
      nutritional status and body composition measured with bioelectrical impedance
      analysis in renal transplant recipients, especially among the Asian population.
      The normal values for these data in renal transplant recipients remain unknown.
      METHODS: All renal transplant recipients with stable graft function who attended
      the outpatient renal transplant clinic in June 2003 were recruited for this cross
      sectional study. Demographic and clinical data were obtained from participating
      patients and their outpatient clinic notes. Body composition and bioelectrical
      impedance data were obtained using the Metron BioScan 916 v3 analyzer. RESULTS:
      Out of a total of 168 renal transplant recipients, 110 participated in this study
      of body composition and bioelectrical impedance for comparison with data from a
      previous study of 419 normal healthy volunteer controls. When compared to the
      healthy Malaysians, renal transplant recipients showed similar body composition
      in terms of body mass index, body cell mass, muscle bulk, percentage of body fat,
      percentage of fat free mass, and percentage of total body water. However, renal
      transplant recipients have more extracellular water, a lower phase angle, and a
      lower reactant. CONCLUSION: Malaysians who have undergone renal transplantation
      have similar body composition to the healthy Malaysians when measurements are
      obtained using bioelectrical impedance analysis.

PMID- 15518797
TI  - Three-legged pair of pants anastomosis: a rare technique for renal
      transplantation.
AB  - Because of the shortage of donors, kidneys previously judged to be unsuitable are
      now accepted for transplantation. Successful engraftment of kidneys with multiple
      renal arteries is one of the challenges and requires meticulous vascular surgical
      technique. In one of our case of renal allograft with three renal arteries, we
      created a single lumen by suturing three arteries together, like a three-legged
      pair of pants. The end of the single lumen was anastomesed to the side of
      external iliac artery. There was brisk diuresis on table after transplantation.
      Postoperatively, the patient had an uneventful course and normal graft function.

PMID- 15518796
TI  - An intraoperative fluorescent imaging system in organ transplantation.
AB  - An intraoperative fluorescent imaging system (SPY system; Novadaq Technologies,
      Inc, Concord, Ontario, Canada) that enables vascular surgeons to confirm the
      location and states of the reconstructed vessels during surgery, has been
      developed in the field of open heart surgery. In this paper, we evaluated the
      usefulness of the SPY system in kidney and liver transplantation. PATIENTS AND
      METHODS: SPY system visualizes arteries and grafts intraoperatively, using
      indocyanine green (ICG) with a portable imaging device. The modality was
      evaluated in 15 patients undergoing kidney (n = 13) or liver (n = 2)
      transplantation with respect to safety, feasibility of use, and image quality.
      Images were generated and acquired with a portable laser diode/infrared camera
      device after injection of 10 mL of ICG (2.5 mg/mL) intravenously. RESULT: There
      was no complication associated with ICG injection or the imaging device. The SPY
      system was easily used during transplant surgery and adequately demonstrated
      reconstructed arteries and patency in all patients. CONCLUSION: The
      intraoperative imaging system enables the surgeon to view, record, and replay
      real-time images of the reconstructed arteries during surgery. The system may
      provide useful information during surgery such as solid organ transplantation
      that requires vascular reconstruction.

PMID- 15518798
TI  - Experimental islet isolation in porcine pancreas with new enzyme Liberase PI.
AB  - The aim of this study was to investigate the results of 20 consecutive porcine
      islet isolations using a new enzyme Liberase PI. Twenty pancreata were procured
      for islet isolation, which was performed using modified Ricordi's method with
      Liberase PI. Quantitation of islet viability staining, insulin stimulation assay,
      intracellular insulin content/DNA, and in vivo transplantability into diabetic
      nude mice were examined for quality control. The results were compared between a
      high-yield group (>2500 IEQ/g pancreas) and a low-yield group (<2500 IEQ/g
      pancreas). Sufficient amount of purified islets (3000 IEQ/g pancreas) were
      obtained using the new brand enzyme Liberase PI. These islets showed good quality
      in structure and functions, which were demonstrated by in vitro and in vivo
      standard assays. Isolation index (IEQ/number) of the low-yield group was lower
      than that of high-yield group (0.75 vs 0.86), which means more fragmentation of
      islets in the low-yield group. There were no differences in function between the
      two groups. In conclusion, we obtained sufficient numbers of viable, functional
      islets from porcine pancreas using a new brand enzyme Liberase PI and low
      temperature isolation technique. However, overdigestion of islets during the
      isolation remains to be overcome. Advance in porcine islet isolation technique
      will in the future make the porcine islet xenotransplantation a reality for the
      cure of diabetes mellitus.

PMID- 15518799
TI  - Cytomegalovirus infection of the graft duodenum and urinary bladder after
      simultaneous pancreas-kidney transplantation.
AB  - Cytomegalovirus (CMV) is an important cause of morbidity after solid organ
      transplantation. We report a case of CMV infection involving the transplanted
      duodenum that developed after simultaneous pancreas-kidney transplantation. The
      patient, a 30-year-old woman with insulin-dependent diabetes undergoing
      hemodialysis due to chronic renal failure, received a simultaneous cadaveric
      pancreas-kidney transplantation. The exocrine secretion was diverted using
      bladder drainage. Immunosuppression was maintained by a combination of
      tacrolimus, mycophenolate mofetil, and steroids together with OKT3 induction.
      Both the donor and the recipient were serologically positive for CMV IgG CMV
      prophylaxis consisted of a short course of parenteral gancyclovir. The patient
      was discharged on postoperative day 39 with normal pancreas and kidney function.
      She presented 2 months after transplantation with hematuria. Cystoscopic pancreas
      allograft biopsy specimens showed evidence of tissue invasive CMV infection in
      the graft duodenum and bladder. The CMV antigenemia test was positive. At 4
      months after transplantation, the patient underwent surgery with the diagnosis of
      acute abdomen. The surgical findings consisted of a diffuse acute purulent
      peritonitis due to perforation of the duodenal graft. We sutured the perforation
      with nonreabsorbable material. The CMV antigenemia test was negative. Eight days
      later, the patient developed massive hematuria. At surgery, the graft was
      removed. The patient was discharged from the hospital with normal renal function.
      Pathological study of the removed graft showed the duodenal segment to have
      multiple wide ulcers with CMV inclusions in epithelial cells.

PMID- 15518800
TI  - Transduction of human islets with the lentiviral vector.
AB  - Establishment of an efficient gene delivery system for human pancreatic beta
      cells is important for the development of diabetes-targeted cell therapies. The
      human immunodeficiency virus type 1 (HIV-1)-derived lentiviral vector is well
      documented to be an effective gene transfer tool for various types of cells.
      Thus, we examined the efficiency of lentivirus-mediated gene delivery for human
      islets. Human islets were isolated using defined protocols for enzymatic
      dissociation and purification using discontinuous Ficoll gradients with a
      refrigerated Cobe 2991 machine. Isolated islets were shipped to Japan,
      cryopreserved for 3 months, and then subjected to transduction. A vesicular
      stomatitis virus G-protein (VSV-G)-pseudotyped lentiviral vector LtV-NLS/LacZ was
      produced in 293T cells under the Fugene6 method. 804G extracellular matrices were
      applied for monolayer formation of islets. Detection of NLS/LacZ expression was
      performed using X-gal staining. Lentiviral transduction was effective in these
      monolayer islets.

PMID- 15518801
TI  - Cobalt-protoporphyrin treatment enhances murine isoislets engraftment.
AB  - To study the effect of treatment with cobalt-protoporphyrin (CoPP) for the
      induction of the heme oxygenase-1 (HO-1) enzyme on islet engraftment donor mice
      received either a single intraperitoneal injection of CoPP (20 mg/kg body weight)
      1 day prior to islet isolation or this injection plus a 9 day posttransplantation
      course of Copp. After a single injection of CoPP, the CoPP-induced islets
      contained higher HO-1 proteins than did the normal islets both at 12 (5.3 +/- 1.5
      vs 0.1 +/- 0.1 ng/mg protein, P < .01) and at 30 hours (6.8 +/- 2.1 vs 0.4 +/-
      0.3 ng/mg protein, P < .05), but not at 56 hours (1.9 +/- 0.8 vs 1.6 +/- 0.8
      ng/mg protein, P > .05). In contrast, diabetic mice that received 75 CoPP-induced
      islets and a 9-day CoPP injection course posttransplantation showed better
      improvement in blood glucose levels and body weights than did the mice that only
      received CoPP-induced islets. Mice of both CoPP-treated groups displayed better
      improvement in glycemic control than mice that received control islets. At 8
      weeks after transplantation, the insulin content of grafts from both CoPP groups
      was significantly higher than that in the control group. In conclusion, CoPP
      treatment for the induction of HO-1 enhances engraftment of islets in a syngeneic
      murine transplantation model.

PMID- 15518802
TI  - Reengineering paramyxovirus tropism.
AB  - Receptor specificity is a critical determinant of viral tropism, but the capacity
      of viruses to switch to alternative receptors has not been extensively studied.
      Here, we engineered the attachment protein of an attenuated measles virus and
      generated truly retargeted viruses that are blind to the native receptors CD46
      and SLAM, but which propagate efficiently and exclusively via alternative
      cellular receptors, epidermal growth factor receptor, or CD38. The engineered
      receptor tropisms were stably maintained during multiple serial virus passage
      without reversion to native receptor usage, even on cells offering the choice of
      both native and alternative receptors. We conclude that paramyxoviruses have a
      remarkably flexible and adaptable entry mechanism.

PMID- 15518804
TI  - The murine cytomegalovirus M73.5 gene, a member of a 3' co-terminal alternatively
      spliced gene family, encodes the gp24 virion glycoprotein.
AB  - We have identified a novel family of five 3' co-terminal transcripts in murine
      cytomegalovirus (MCMV) arranged in a tail-to-tail orientation with respect to the
      MCMV glycoprotein H (gH) gene M75. They share the same exon 2 sequence but
      possess different exon 1 sequences. Two of these spliced transcripts (M73) encode
      the MCMV homolog of glycoprotein N (gN) entirely within exon 1. Two other
      transcripts designated M73.5 encode a previously described virion glycoprotein
      gp24 that shares its first 20 amino acids with gN, but which has another 64 amino
      acids encoded within exon 2. The fifth transcript, designated m60, has an 80-bp
      exon 1 near the MCMV oriLyt region 10.8 kb upstream of exon 2. Both MCMV M73.5
      and m60 encode type II glycoproteins expressed at the cell surface. Their shared
      exon 2 coding sequences likely represent the highly conserved region of an as yet
      unidentified betaherpesvirus-specific glycoprotein species.

PMID- 15518803
TI  - Use of a Clostridium perfringens vector to express high levels of SIV p27 protein
      for the development of an oral SIV vaccine.
AB  - Clostridium perfringens is a normal bacterial flora of the small and large
      intestines of humans and other animals. The current study investigates the
      potential use of a noncytotoxic C. perfringens as an oral vaccine vehicle for
      expression and intestinal delivery of a large amount of SIV antigens. Here we
      report the construction of a recombinant C. perfringens vaccine vector expressing
      high levels of SIV p27 during sporulation. Following oral administration of this
      recombinant C. perfringens vaccine vector to mice, large amounts of intact p27
      protein were detected in the terminal ileum where the majority of Peyer's Patches
      (PPs) are located. Furthermore, dendritic cells (DCs) beneath the mucosal surface
      in the PPs were able to capture SIV p27 antigen, when PPs were exposed to C.
      perfringens expressing SIV p27 antigen. In addition, uptake of C. perfringens was
      able to induce maturation of mouse DCs. These results support the potential use
      of C. perfringens as an oral SIV/HIV vaccine vector.

PMID- 15518805
TI  - Differential roles of CCL2 and CCR2 in host defense to coronavirus infection.
AB  - The CC chemokine ligand 2 (CCL2, monocyte chemoattractant protein-1) is important
      in coordinating the immune response following microbial infection by regulating T
      cell polarization as well as leukocyte migration and accumulation within infected
      tissues. The present study examines the consequences of mouse hepatitis virus
      (MHV) infection in mice lacking CCL2 (CCL2(-/-)) in order to determine if
      signaling by this chemokine is relevant in host defense. Intracerebral infection
      of CCL2(-/-) mice with MHV did not result in increased morbidity or mortality as
      compared to either wild type or CCR2(-/-) mice and CCL2(-/-) mice cleared
      replicating virus from the brain. In contrast, CCR2(-/-) mice displayed an
      impaired ability to clear virus from the brain that was accompanied by a
      reduction in the numbers of antigen-specific T cells as compared to both CCL2(-/
      ) and wild-type mice. The paucity in T cell accumulation within the central
      nervous system (CNS) of MHV-infected CCR2(-/-) mice was not the result of either
      a deficiency in antigen-presenting cell (APC) accumulation within draining
      cervical lymph nodes (CLN) or the generation of virus-specific T cells within
      this compartment. A similar reduction in macrophage infiltration into the CNS was
      observed in both CCL2(-/-) and CCR2(-/-) mice when compared to wild-type mice,
      indicating that both CCL2 and CC chemokine receptor 2 (CCR2) contribute to
      macrophage migration and accumulation within the CNS following MHV infection.
      Together, these data demonstrate that CCR2, but not CCL2, is important in host
      defense following viral infection of the CNS, and CCR2 ligand(s), other than
      CCL2, participates in generating a protective response.

PMID- 15518806
TI  - Markedly reduced severity of Dengue virus infection in mosquito cell cultures
      persistently infected with Aedes albopictus densovirus (AalDNV).
AB  - AalDNV-infected C6/36 cells serially passaged for over 10 weeks showed a decline
      in percentage of anti-AalDNV-positive cells (APC) from an initial 92% to
      approximately 20%. Cultures of persistent APC were indistinguishable from
      uninfected cultures by direct microscopy but most stained cells from early APC
      passages had enlarged nuclei with eosinophilic inclusions, while late APC
      passages had few and naive cells none. Super challenge of persistent APC cultures
      did not increase percentage APC and supernatants from persistent APC cultures
      gave low APC (40%) in naive C6/36 cell cultures. When challenged with dengue
      virus serotype 2 (DEN-2), naive C6/36 cells showed severe cytopathic effects
      (CPE) and high mortality within 4 days, as did early passage APC cultures.
      Remarkably, DEN-2 infections in persistent APC cultures were much less severe,
      being characterized by reduced DEN-2 infection percentage, retarded DEN-2 virion
      production, no CPE and no significant mortality. Reasons for rapid reduction in
      APC and resistance to superinfection upon serial passage remain unproven but may
      relate to production of AalDNV-defective interfering particles (DIP) by molecular
      mechanisms still open to speculation. More difficult to explain is cross
      protection against DEN-2-induced mortality seen in persistent APC cultures.
      However, by comparison to work on shrimp viruses, we speculate that this may
      involve blockage of viral-triggered apoptosis. The phenomena described raise
      questions regarding the potential for persistent infections by unknown viruses to
      confound experimental results with insect cell lines.

PMID- 15518807
TI  - No apoptotic deaths and different levels of inductions of inflammatory cytokines
      in alveolar macrophages infected with influenza viruses.
AB  - Influenza viruses are reported to infect mainly the respiratory tract epithelium
      of hosts. Our studies in a pig model show that influenza A viruses infect
      alveolar macrophages that constitutively reside in the respiratory tract, without
      causing apoptosis. Tumor necrosis factor alpha was the inflammatory cytokine most
      highly induced in these macrophages. In vivo, alveolar macrophages infected with
      human H3N2 influenza virus showed greater expression of tumor necrosis factor
      alpha than did alveolar macrophages infected with human H1N1 influenza virus.
      Induction of specific inflammatory cytokine such as TNF-alpha is a polygenic
      trait that involves the HA and NA genes. Markedly elevated expression of tumor
      necrosis factor alpha may be responsible for the high mortality rate caused by
      H3N2 influenza virus infection in elderly patients.

PMID- 15518808
TI  - Low-level HIV infection of plasmacytoid dendritic cells: onset of cytopathic
      effects and cell death after PDC maturation.
AB  - Plasmacytoid dendritic cells (PDC), the natural type-1 interferon (IFN) producing
      cells, are part of the innate immune defense against human immunodeficiency virus
      (HIV). PDC numbers are reduced in advanced stages of infection. These cells can
      be infected in vivo by HIV since highly purified PDC showed evidence of
      infectious HIV. Moreover, when PDC derived from uninfected donors were exposed to
      high-titered HIV isolates, productive infection occurred although with low-level
      replication. Using real-time amplification, PDC and unstimulated CD4+ cells were
      found equally susceptible to HIV infection; however, HIV replication was
      considerably limited in the PDC. Virus replication was enhanced after PDC
      treatment with CD40L and antibodies against IFN-alpha, most likely reflecting the
      reduction in IFN-alpha activity. On maturation, the infected PDC showed
      multinuclear cell syncytia formation and death. These findings indicate that PDC
      can be reservoirs for HIV dissemination and that HIV infection of PDC can
      contribute to their decline.

PMID- 15518809
TI  - Recombinant Sendai viruses with L1618V mutation in their L polymerase protein
      establish persistent infection, but not temperature sensitivity.
AB  - The Sendai virus pi strain (SeVpi) isolated from cells persistently infected with
      SeV shows mainly two phenotypes: (1) temperature sensitivity and (2) an ability
      of establishing persistent infection (steady state). Three amino acid
      substitutions are found in the Lpi protein and are located at aa 1088, 1618, and
      1664. Recombinant SeV(Lpi) (rSeV(Lpi)) having all these substitutions is
      temperature sensitive and is capable of establishing persistent infection (steady
      state). rSeVs carrying the fragment containing L1618V show both phenotypes.
      rSeV(L1618V), in which leucine at aa 1618 is replaced with valine, has the
      ability of establishing persistent infection, but is not a temperature-sensitive
      mutant, indicating that the ability of a virus to establish persistent infection
      can be separated from temperature sensitivity. The amino acid change at 1618(L-
      >V) coexisting with aa 1169 threonine is required for acquirement of a
      temperature-sensitive phenotype. Three amino acid substitutions are also found in
      the Ppi protein, but rSeV(Ppi) does not show these phenotypes.

PMID- 15518810
TI  - Human immunodeficiency virus type 1 Nef protein mediates neural cell death: a
      neurotoxic role for IP-10.
AB  - HIV-1 Nef is expressed in astrocytes, but a contribution to neuropathogenesis and
      the development of HIV-associated dementia (HAD) remains uncertain. To determine
      the neuropathogenic actions of the HIV-1 Nef protein, the brain-derived (YU-2)
      and blood-derived (NL4-3) Nef proteins were expressed in neural cells using an
      alphavirus vector, which resulted in astrocyte death (P < 0.001). Supernatants
      from Nef-expressing astrocytes also caused neuronal death, suggesting the release
      of neurotoxic molecules by astrocytes. Analysis of pro-inflammatory gene
      induction in astrocytes expressing Nef revealed increased IP-10 mRNA expression
      (4000-fold) that was Nef sequence dependent. Recombinant IP-10 caused selective
      cell death in neurons (P < 0.001) but not astrocytes, and the cytotoxicity of
      supernatant from astrocytes expressing Nef YU-2 was blocked by an antibody
      directed against the chemokine receptor CXCR3 (P < 0.001). SCID/NOD mice
      implanted with a Nef YU-2-expressing vector displayed abnormal motor behavior (P
      < 0.05), neuroinflammation, and neuronal loss relative to controls. Analysis of
      mRNA levels in brains from patients with HAD also revealed increased expression
      of IP-10 (P < 0.05), which was confirmed by immunoreactivity detected principally
      in astrocytes. Phylogenetic and protein structure analyses of Nef sequences
      derived from HIV/AIDS patients with and without HAD suggested viral evolution
      toward a neurotropic Nef protein. These results indicate that HIV-1 Nef
      contributes to neuropathogenesis by directly causing astrocyte death together
      with indirect neuronal death through the cytotoxic actions of IP-10 on neurons.
      Furthermore, Nef molecular diversity was evident in brain tissue among patients
      with neurological disease and which may influence IP-10 production by astrocytes.

PMID- 15518811
TI  - Conserved residues in the coiled-coil pocket of human immunodeficiency virus type
      1 gp41 are essential for viral replication and interhelical interaction.
AB  - The human immunodeficiency virus type 1 (HIV-1) gp41 plays an important role in
      mediating the fusion of HIV with host cells. During the fusion process, three N
      terminal helices and three C-terminal helices pack in an anti-parallel direction
      to form a six-helix bundle. X-ray crystallographic analysis of the gp41 core
      demonstrated that within each coiled-coil interface, there is a deep and large
      pocket, formed by a cluster of residues in the N-helix coiled-coil. In this
      report, we systematically analyzed the role of seven conserved residues that are
      either lining or packing this pocket on the infectivity and interhelical
      interaction using novel approaches. Our results show that residues L568, V570,
      W571, and K574 of the N-helix that are lining the side chain and right wall of
      the pocket are important for establishing a productive infection. Mutations V570A
      and W571A completely abolished replication, while replication of the L568A and
      K574A mutants was significantly attenuated relative to wild type. Similarly,
      residues W628, W631, and I635 of the C-helix that insert into the pocket are
      essential for infectivity. The impaired infectivity of these seven mutants is in
      part attributed to the loss in binding affinity of the interhelical interaction.
      Molecular modeling of the crystal structure of the coiled-coil further shows that
      alanine substitution of those residues disrupts the hydrophobic interaction
      between the N- and C-helix. These results suggest that the conserved residues in
      the coiled-coil domain play a key role in HIV infection and this coiled-coil
      pocket is a good target for development of inhibitors against HIV. In addition,
      our data indicate that the novel fluorescence polarization assay described in
      this study could be valuable in screening for inhibitors that block the
      interhelical interaction and HIV entry.

PMID- 15518812
TI  - Protein interactions among the vaccinia virus late transcription factors.
AB  - The viral proteins A1L, A2L, G8R, and H5R positively modulate vaccinia virus late
      gene expression. Host-encoded proteins hnRNP A2 and RBM3 may also interact with
      these viral factors to influence late gene expression. In these studies, a yeast
      two-hybrid screen and in vitro pulldown and crosslinking experiments were used to
      investigate protein--protein interactions among these factors. These studies
      confirmed a previous observation that G8R interacts with itself and A1L. However,
      self-interactions of A1L and H5R, and interactions between A2L and G8R, A2L and
      H5R, and H5R and G8R were also observed. In addition, the proteins hnRNP A2 and
      RBM3 both showed some interaction with A2L. Illustration of these interactions is
      a step toward understanding the architecture of the late gene transcription
      complex as it occurs in poxviruses.

PMID- 15518813
TI  - Baculovirus proteins IE-1, LEF-3, and P143 interact with DNA in vivo: a
      formaldehyde cross-linking study.
AB  - IE-1, LEF-3, and P143 are three of six proteins encoded by Autographa californica
      nucleopolyhedrovirus (AcMNPV) essential for baculovirus DNA replication in
      transient replication assays. IE-1 is the major baculovirus immediate early
      transcription regulator. LEF-3 is a single-stranded DNA binding protein (SSB) and
      P143 is a DNA helicase protein. To investigate their interactions in vivo, we
      treated AcMNPV-infected Spodoptera frugiperda cells with formaldehyde and
      separated soluble proteins from chromatin by cell fractionation and cesium
      chloride equilibrium centrifugation. Up to 70% of the total LEF-3 appeared in the
      fraction of soluble, probably nucleoplasmic proteins, while almost all P143 and
      IE-1 were associated with viral chromatin in the nucleus. This suggests that LEF
      3 is produced in quantities that are higher than needed for the coverage of
      single stranded regions that arise during viral DNA replication and is consistent
      with the hypothesis that LEF-3 has other functions such as the localization of
      P143 to the nucleus. Using a chromatin immunoprecipitation procedure, we present
      the first direct evidence of LEF-3, P143, and IE-1 proteins binding to closely
      linked sites on viral chromatin in vivo, suggesting that they may form
      replication complexes on viral DNA in infected cells.

PMID- 15518814
TI  - Identification of the 5' sequences required for incorporation of an engineered
      ssRNA into the Reovirus genome.
AB  - Using a reovirus reverse genetics system, we have identified the 5' sequences
      required of an engineered s2 ssRNA for efficient incorporation into the dsRNA
      genome of Reovirus. Employing an engineered, functionally active reovirus S2/CAT
      gene retaining the first 198 5' terminal nucleotides and the last 284 3' terminal
      nucleotides of the wild-type S2 segment, we have determined the 5' sequence
      required by a ssRNA to be recognized, replicated to dsRNA, and stably
      incorporated into an infectious reovirus. The 5' sequence retains 96 nucleotides
      of the wild-type s2 ssRNA and a predicted sequence-structure element. Within
      these 96 nucleotides, we have identified three nucleotides A-U-U at positions 79
      81 that are essential for the incorporation of in vitro-generated ssRNAs into new
      reovirus progeny viral particles. This study establishes a firm foundation for
      additional investigation into the assortment and encapsidation mechanism of all
      10 ssRNAs into the dsRNA genome of reovirus.

PMID- 15518815
TI  - The role of tumor necrosis factor in modulating responses of murine embryo
      fibroblasts by flavivirus, West Nile.
AB  - Murine embryo fibroblasts (MEF) transcribe tumor necrosis factor (TNF) mRNA and
      secrete soluble TNF in response to infection by West Nile virus (WNV) and TNF was
      demonstrated to be protective against WNV infection in vitro. TNF is not required
      for the WNV-induced upregulation of MHC-I expression on MEF, as TNF deficiency
      did not affect the upregulation of major histocompatibility complex class I (MHC
      I) by WNV. Furthermore, NF-kappaB was activated by WNV in TNF-deficient MEF,
      demonstrating that WNV induces NF-kappaB activation in a TNF-independent manner.
      The subunits of NF-kappaB activated by TNF and WNV differed, WNV-activated a
      p65/p50 NF-kappaB complex while TNF-activated NF-kappaB was composed of p65, p50,
      and c-Rel. Furthermore, TNF-induced activation of NF-kappaB occurred earlier than
      WNV-induced NF-kappaB activation. The data demonstrate that WNV infection of MEF
      is associated with TNF production, but the WNV-induced activation of NF-kappaB
      and subsequent upregulation of MHC-I by WNV is TNF-independent.

PMID- 15518816
TI  - Human immunodeficiency virus 1 favors the persistence of infection by activating
      macrophages through TNF.
AB  - Macrophages play a major role in HIV-1 persistence. In the present paper, we
      demonstrate that the absence of apoptosis in HIV-1-infected primary human
      monocyte-differentiated macrophages (MDM) correlates with an increase in anti
      apoptotic (Bcl-2 and Bcl-x(L)) and a decrease in pro-apoptotic (Bax and Bad)
      proteins. This is associated with macrophage activation as shown by tumor
      necrosis factor (TNF) production and NF-kappaB activation upon infection. TNF
      production was shown to be involved in the upregulation of Bcl-2 and Bcl-x(L)
      because this increase was abolished by an anti-TNF anti-serum or an inhibitor of
      TNF synthesis. In parallel, inhibition of TNF production induced an increase in
      the number of apoptotic cells. Furthermore, using an inhibitor of NF-kappaB
      activation, we demonstrated that TNF-induced upregulation of Bcl-x(L) and Bcl-2
      occurs, respectively, through a NF-kappaB-dependent and an NF-kappaB-independent
      pathway.

PMID- 15518817
TI  - Coxsackievirus B3 infection and type 1 diabetes development in NOD mice:
      insulitis determines susceptibility of pancreatic islets to virus infection.
AB  - Group B coxsackieviruses (CVB) are believed to trigger some cases of human type 1
      diabetes (T1D), although the mechanism by which this may occur has not been
      shown. We demonstrated previously that inoculation of young nonobese diabetic
      (NOD) mice with any of several different CVB strains reduced T1D incidence. We
      also observed no evidence of CVB replication within islets of young NOD mice,
      suggesting no role for CVB in T1D induction in the NOD mouse model. The failure
      to observe CVB replication within islets of young NOD mice has been proposed to
      be due to interferon expression by insulin-producing beta cells or lack of
      expression of the CVB receptor CAR. We found that CAR protein is detectable
      within islets of young and older NOD mice and that a CVB3 strain, which expresses
      murine IL-4, can replicate in islets. Mice inoculated with the IL-4 expressing
      CVB3 chimeric strain were better protected from T1D onset than were mock-infected
      control mice despite intraislet viral replication. Having demonstrated that CVB
      can replicate in healthy islets of young NOD mice when the intraislet environment
      is suitably altered, we asked whether islets in old prediabetic mice were
      resistant to CVB infection. Unlike young mice in which insulitis is not yet
      apparent, older NOD mice demonstrate severe insulitis in all islets. Inoculating
      older prediabetic mice with different pathogenic CVB strains caused accelerated
      T1D onset relative to control mice, a phenomenon that was preceded by detection
      of virus within islets. Together, the results suggest a model for resolving
      conflicting data regarding the role of CVB in human T1D etiology.

PMID- 15518818
TI  - Activation of HTLV-I gene transcription by protein tyrosine phosphatase
      inhibitors.
AB  - Human T-cell leukemia virus type I (HTLV-I) transcription generally depends on
      the ability of the viral Tax protein to bind the CREB transcription factor and
      form an active complex by recruiting CBP/p300 coactivators to the long terminal
      repeat (LTR). Studies have demonstrated that T-cell activating agents that
      stimulate CREB are potent inducers of HTLV-I transcription. Herein, we
      demonstrate that bpV[pic], a protein tyrosine phosphatase (PTP) inhibitor
      activates the HTLV-I LTR in the presence and absence of Tax expression. Optimal
      activation occurred at 8 h and was synergistic with forskolin or PGE(2). Infected
      cell lines and cells transfected with HTLV-I proviral DNA were equally responsive
      to the synergistic effect of bpV and forskolin on HTLV-I gene expression.
      Activation of the LTR by bpV[pic] was T-cell receptor-independent, but required
      ZAP70, calcineurin activity and functional calcium entry. Inhibition of the SHP-1
      PTP was suggested to be important. Transfection experiments with a CREB dominant
      negative mutant and with isolated TRE1- or CREB-responsive reporter constructs
      and treatment with the MDL-12,330A adenylate cyclase inhibitor all supported the
      involvement of a CREB/ATF family member in this bpV-dependent activation of the
      HTLV-I LTR, although CREB itself did not seem to be involved. Analysis of HTLV-I
      reporter constructs containing mutated CREB-binding sites also implied the
      involvement of another element in this activation. These results demonstrate for
      the first time a powerful effect of PTP inhibitors on HTLV-I LTR activity and
      suggest participation of both CREB-dependent and -independent pathways in this
      activation.

PMID- 15518819
TI  - Improved isolation of undersampled bacteriophages: finding of distant terminase
      genes.
AB  - Isolation and characterization of new environmental bacteriophages are performed
      for (1) analyzing microbial evolution and ecology and (2) delivering biological
      therapy. The sampling of environmental bacteriophages appears, however, to be
      limited by the procedure (usually liquid enrichment culture) used to propagate
      them. An alternative, less competitive procedure is developed here for the
      purpose of isolating new bacteriophages. This procedure involves extraction
      directly into and then propagation in a dilute agarose gel. Adaptations of this
      procedure are used to avoid repeated isolation of the same bacteriophage. Some
      newly isolated bacteriophages grow so poorly that they appear inaccessible to
      liquid enrichment culture. Four comparatively high titer bacteriophages were
      isolated and characterized by a genomic sequence survey. Some had genomes with
      extremely distant relationships to those of other bacteriophages, based on a tree
      built from the large terminase genes. These methods find novel genomes by rapidly
      isolating and screening diverse bacteriophages.

PMID- 15518820
TI  - An orthologue of the cor gene is involved in the exclusion of temperate lambdoid
      phages. Evidence that Cor inactivates FhuA receptor functions.
AB  - A new set of lambdoid phages (mEp) classified into different immunity groups was
      previously described. Phages mEp213, mEp237, and mEp410 were unable to grow in
      mEp167 lysogenic cells, presumably due to an exclusion mechanism expressed
      constitutively by the mEp167 repressed prophage. In this work, to analyze the
      exclusion phenomenon, we constructed a genomic library from mEp167 phage in a
      pPROEX derivative plasmid. A DNA fragment containing an open reading frame for a
      77 amino acid polypeptide was selected by its ability to confer resistance to
      heteroimmune phage infection. This ORF shows high amino acid sequence identity
      with putative Cor proteins of phages HK022, phi80 and N15. Cells expressing the
      mEp167 cor gene from a plasmid (Cor(+) phenotype) excluded 13 of 20 phages from
      different infection immunity groups. This exclusion was observed in both tonB(-)
      and tonB(+) cells. Lambdoid mEp phages that were excluded in these cells were
      unable to infect cells defective in the outer membrane FhuA receptor (fhuA(-)).
      Thus, Cor-mediated exclusion was only observed in fhuA(+) cells. Phage production
      after DNA transfection or the spontaneous induction of mEp prophage in Cor(+)
      cells was not blocked. In addition, ferrichrome uptake, which is mediated by
      FhuA, was inhibited in Cor(+) cells. Our results show that not only phage
      infection via FhuA but also a FhuA transport activity (ferrichrome uptake) are
      inhibited by Cor, presumably by inactivation of FhuA.

PMID- 15518821
TI  - Long-term infection with retroviral structural gene vector provides protection
      against bovine leukemia virus disease in rabbits.
AB  - Bovine leukemia virus (BLV) infection of rabbits is a tractable model system to
      evaluate vaccination strategies against lymphotropic retroviruses, which
      represent a global human health problem. We have previously developed genetically
      simplified BLV structural gene vector (SGV) that replicates BLV structural and
      enzymatic genes independently of BLV regulatory and accessory genes. Results of a
      20-month study in a rabbit model demonstrated that BLV SGV induces an antiviral
      immunological response and lacks pathogenicity. Here, these chronically infected
      BLV SGV rabbits are assessed in a proof-of-principle study of preventative
      vaccination against challenge with pathogenic BLV. This study commences 24 months
      after BLV SGV inoculation and proceeds for an additional 20 months. The
      previously characterized BLV SGV rabbits and age-matched control rabbits were
      challenged with 1 x 10(8) fetal lamb kidney/BLV producer cells. BLV SGV rabbits
      seroconverted upon BLV challenge, but did not progress to BLV infection nor
      clinical disease. By contrast, naive rabbits became infected and succumbed to
      lymphotropic disease. Our findings provide proof-of-principle that chronic
      infection with BLV SGV induces protection against BLV infection. The data
      indicate that SGV based on HTLV or HIV is a promising approach against
      lymphotropic disease by human retroviruses.

PMID- 15518822
TI  - Complementarity between RNA dimerization elements favors formation of functional
      heterozygous murine leukemia viruses.
AB  - The cis-elements that direct packaging and dimerization of retroviral RNAs
      overlap, and it has been suggested that dimerization is required for RNA
      packaging. This also implies that heterodimerization would be necessary for co
      packaging and recombination. Moreover, co-packaging of distinct RNAs may be
      reduced if incapable of heterodimerizing. In this study, we have designed a novel
      two-vector rescue system in which co-packaging and interstrand transfer are
      necessary for transduction. Thus, the rescue titer is a measure of the ability of
      a given vector combination to co-package and subsequently generate a provirus. In
      the current MLV-based set-up, we explored Akv- and MLV-like-endogenous virus
      (MLEV)-derived vectors with modulated dimerization signals. Results show that
      rescue is influenced by competition at the level of RNA packaging, as well as
      complementarity between dimerization elements. Altogether, the results support
      the hypothesis that complementarity between dimerization elements may favor co
      packaging of distinct retroviral RNAs.

PMID- 15518823
TI  - Mutant hepatitis B virus surface antigens (HBsAg) are immunogenic but may have a
      changed specificity.
AB  - Mutant hepatitis B virus with substitutions within the coding region for HBV
      surface antigen (HBsAg) has been found naturally in chronic carriers. It is
      therefore important to clarify whether the identified substitutions within the
      HBsAg have impact on the antigenicity and immunogenicity of HBsAg. A total of
      nine mutated HBV s-genes with single representative mutations were generated by
      site-directed mutagenesis and subcloned into an expression vector. The binding of
      polyclonal and monoclonal antibodies to these mutant HBsAg (mtHBsAg) was tested
      by immunofluorescence (IF) staining of cells transfected with the expression
      vectors. The amino acid (aa) substitutions like G145R, F134S, and C147W affected
      the binding of anti-HBs antibodies to corresponding mtHBsAg to different extents.
      The impact of aa substitutions G145R and F134S on the immunogenicity was accessed
      by genetic immunization of mice with vectors expressing middle HBsAg with the
      corresponding mutations. The immunized mice developed antibodies to recombinant
      HBsAg containing the HBV preS region and HBsAg-specific cytotoxic T-cell.
      However, the development of antibody response to wild-type small HBsAg was
      significantly impaired by the aa substitutions in HBsAg. Based on this fact, we
      further investigated whether the mtHBsAg with the aa substitution G145R is able
      to induce mutant-specific antibody responses. Strikingly, serum samples from mice
      immunized with mtHBsAg with G145R recognized plasma-derived mtHBsAg. Two mouse
      MAbs specific to mtHBsAg were generated. One MAb recognized mtHBsAg with G145R
      but not wild type and other mtHBsAg. We conclude that HBsAg with aa substitutions
      are immunogenic but may have a changed fine specificity.

PMID- 15518824
TI  - Potency of HIV-1 envelope glycoprotein gp120 antibodies to inhibit the
      interaction of DC-SIGN with HIV-1 gp120.
AB  - The interaction of DC-SIGN with gp120 provides an attractive target for
      intervention of HIV-1 transmission. Here, we have investigated the potency of
      gp120 antibodies to inhibit the DC-SIGN-gp120 interaction. We demonstrate that
      although the V3 loop is not essential for DC-SIGN binding, antibodies against the
      V3 loop partially inhibit DC-SIGN binding, suggesting that these antibodies
      sterically hinder DC-SIGN binding to gp120. Polyclonal antibodies raised against
      non-glycosylated gp120 inhibited both low and high avidity DC-SIGN-gp120
      interactions in contrast to polyclonal antibodies raised against glycosylated
      gp120. Thus, glycans present on gp120 may prevent the generation of antibodies
      that block the DC-SIGN-gp120 interactions. Moreover, the polyclonal antibodies
      against non-glycosylated gp120 efficiently inhibited HIV-1 capture by both DC
      SIGN transfectants and immature dendritic cells. Therefore, non-glycosylated
      gp120 may be an attractive immunogen to elicit gp120 antibodies that block the
      binding to DC-SIGN. Furthermore, we demonstrate that DC-SIGN binding to gp120
      enhanced CD4 binding, suggesting that DC-SIGN induces conformational changes in
      gp120, which may provide new targets for neutralizing antibodies.

PMID- 15518825
TI  - Comprehensive sequence analysis of the E1A proteins of human and simian
      adenoviruses.
AB  - Despite extensive study of human adenovirus type 5 E1A, surprisingly little is
      known about the E1A proteins of other adenoviruses. We report here a
      comprehensive analysis of the sequences of 34 E1A proteins. These represent all
      six primate adenovirus subgroups and include all human representatives of
      subgroups A, C, E, and F, eight from subgroup B, nine from subgroup D, and seven
      simian adenovirus E1A sequences. We observed that many, but not all, functional
      domains identified in human adenovirus type 5 E1A are recognizably present in the
      other E1A proteins. Importantly, we identified highly conserved sequences without
      known activities or binding partners, suggesting that previously unrecognized
      determinants of E1A function remain to be uncovered. Overall, our analysis forms
      a solid foundation for future study of the activities and features of the E1A
      proteins of different serotypes and identifies new avenues for investigating E1A
      function.

PMID- 15518826
TI  - Human Parvovirus B19 nonstructural protein transactivates the p21/WAF1 through
      Sp1.
AB  - The expression of human Parvovirus B19 nonstructural protein 1 (NS1) induces cell
      cycle arrest at the G1 phase and is accompanied by increased expression of the
      cyclin-dependent kinase inhibitor, p21/WAF1. Here, we provide direct evidence
      that NS1 mediates the transactivation of p21/WAF1. Up-regulation of p21/WAF1 by
      wild-type NS1 but not an NS1 mutant deleted of its NTP binding motif was
      observed. We also demonstrated that the wild-type NS1 is unable to induce G1
      arrest in p21-deficient cells. Using reporter plasmids containing various mutants
      of the p21/WAF1 promoter, luciferase assay further revealed that the binding
      sites of the promoter to the transcription factor Sp1 are critical for NS1
      mediated transactivation. Indeed Sp1 interacts only with the wild-type NS1 but
      not the NS1 mutant. These results indicate a cooperative contribution of NS1 and
      Sp1 to the transactivation of p21/WAF1, which leads to G1 arrest.

PMID- 15518827
TI  - Sustained transmission of dengue virus type 1 in the Pacific due to repeated
      introductions of different Asian strains.
AB  - Outbreaks of dengue due to dengue virus type 1 (DENV-1) occurred almost
      simultaneously in 2001 in Myanmar and at multiple sites almost 10,000 km away in
      the Pacific. Phylogenetic analyses of the E protein genes of DENV-1 strains
      recovered from Asia and the Pacific revealed three major viral genotypes (I, II,
      and III) with distinct clades within each. The majority of strains from the
      Pacific and Myanmar, and a number of other Asian strains fell into genotype I.
      Genotype II comprised a smaller set of Asian and Pacific strains, while genotype
      III contained viruses from diverse geographical localities. These analyses
      suggested that the continuing outbreak of dengue in the Pacific has been due to
      multiple, direct, introductions of dengue viruses from a variety of locations in
      Asia followed by local transmission. There was no evidence that the introduction
      of these viruses into the Pacific was associated with any adaptive changes in the
      E protein of the viruses.

PMID- 15518828
TI  - Glutathione, altruistic metabolite in fungi.
AB  - Glutathione (GSH; gamma-L-glutamyl-L-cysteinyl-glycine), a non-protein thiol with
      a very low redox potential (E'0 = 240 mV for thiol-disulfide exchange), is
      present in high concentration up to 10 mM in yeasts and filamentous fungi. GSH is
      concerned with basic cellular functions as well as the maintenance of
      mitochondrial structure, membrane integrity, and in cell differentiation and
      development. GSH plays key roles in the response to several stress situations in
      fungi. For example, GSH is an important antioxidant molecule, which reacts non
      enzymatically with a series of reactive oxygen species. In addition, the response
      to oxidative stress also involves GSH biosynthesis enzymes, NADPH-dependent GSH
      regenerating reductase, glutathione S-transferase along with peroxide-eliminating
      glutathione peroxidase and glutaredoxins. Some components of the GSH-dependent
      antioxidative defence system confer resistance against heat shock and osmotic
      stress. Formation of protein-SSG mixed disulfides results in protection against
      desiccation-induced oxidative injuries in lichens. Intracellular GSH and GSH
      derived phytochelatins hinder the progression of heavy metal-initiated cell
      injuries by chelating and sequestering the metal ions themselves and/or by
      eliminating reactive oxygen species. In fungi, GSH is mobilized to ensure
      cellular maintenance under sulfur or nitrogen starvation. Moreover, adaptation to
      carbon deprivation stress results in an increased tolerance to oxidative stress,
      which involves the induction of GSH-dependent elements of the antioxidant defence
      system. GSH-dependent detoxification processes concern the elimination of toxic
      endogenous metabolites, such as excess formaldehyde produced during the growth of
      the methylotrophic yeasts, by formaldehyde dehydrogenase and methylglyoxal, a by
      product of glycolysis, by the glyoxalase pathway. Detoxification of xenobiotics,
      such as halogenated aromatic and alkylating agents, relies on glutathione S
      transferases. In yeast, these enzymes may participate in the elimination of toxic
      intermediates that accumulate in stationary phase and/or act in a similar fashion
      as heat shock proteins. GSH S-conjugates may also form in a glutathione S
      transferases-independent way, e.g. through chemical reaction between GSH and the
      antifugal agent Thiram. GSH-dependent detoxification of penicillin side-chain
      precursors was shown in Penicillium sp. GSH controls aging and autolysis in
      several fungal species, and possesses an anti-apoptotic feature.

PMID- 15518829
TI  - The role of the flavodiiron proteins in microbial nitric oxide detoxification.
AB  - The flavodiiron proteins (first named as A-type flavoproteins) constitute a large
      superfamily of enzymes, widespread among anaerobic and facultative anaerobic
      prokaryotes, from both the Archaea and Bacteria domains. Noticeably, genes
      encoding for homologous enzymes are also present in the genomes of some
      pathogenic and anaerobic amitochondriate protozoa. The fingerprint of this enzyme
      family is the conservation of a two-domain structural core, built by a metallo
      beta-lactamase-like domain, at the N-terminal region, harbouring a non-heme
      diiron site, and a flavodoxin-like domain, containing one FMN moiety. These
      enzymes have a significant nitric oxide reductase activity, and there is
      increasing evidence that they are involved in microbial resistance to nitric
      oxide. In this review, we will discuss available data for this novel family of
      enzymes, including their physicochemical properties, structural and phylogenetic
      analyses, enzymatic properties and the molecular genetic approaches so far used
      to tackle their function.

PMID- 15518830
TI  - Stress responsive bacteria: biosensors as environmental monitors.
AB  - The delicate and dynamic balance of the physiological steady state and its
      maintenance is well characterized by studies of bacterial stress response.
      Through the use of genetic analysis, numerous stress regulons, their
      physiological regulators and their biochemical processes have been delineated. In
      particular, transcriptionally activated stress regulons are subjects of study and
      application. These regulons include those that respond to macromolecular damage
      and toxicity as well as to nutrient starvation. The convenience of reporter gene
      fusions has allowed the creation of biosensor strains, resulting from the fusion
      of stress-responsive promoters with a variety of reporter genes. Such cellular
      biosensors are being used for monitoring dynamic systems and can report the
      presence of environmental stressors in real time. They provide a greater range of
      sensitivity, e.g. to sub-lethal concentrations of toxicants, than the simple
      assessment of cell viability. The underlying physiological context of the
      reporter strains results in the detection of bioavailable concentrations of both
      toxicants and nutrients. Culture conditions and host strain genotypes can be
      customized so as to maximize the sensitivity of the strain for a particular
      application. Collections of specific strains that are grouped in panels are used
      to diagnose targets or mode of action for unknown toxicants. Further application
      in massive by parallel DNA and gene fusion arrays greatly extends the information
      available for diagnosis of modes of action and may lead to development of novel
      high-throughput screens. Future studies will include more panels, arrays, as well
      as single reporter cell detection for a better understanding of the population
      heterogeneity during stress response. New knowledge of physiology gained from
      further studies of novel systems, or using innovative methods of analysis, will
      undoubtedly yield still more useful and informative environmental biosensors.

PMID- 15518831
TI  - Bacterial Na+ - or H+ -coupled ATP synthases operating at low electrochemical
      potential.
AB  - In certain strictly anaerobic bacteria, the energy for growth is derived entirely
      from a decarboxylation reaction. A prominent example is Propionigenium modestum,
      which converts the free energy of the decarboxylation of (S)-methylmalonyl-CoA to
      propionyl-CoA (DeltaG degrees =-20.6 kJ/mol) into an electrochemical Na(+) ion
      gradient across the membrane. This energy source is used as a driving force for
      ATP synthesis by a Na(+)-translocating F(1)F(0) ATP synthase. According to
      bioenergetic considerations, approximately four decarboxylation events are
      necessary to support the synthesis of one ATP. This unique feature of using Na(+)
      instead of H(+) as the coupling ion has made this ATP synthase the paradigm to
      study the ion pathway across the membrane and its relationship to rotational
      catalysis. The membrane potential (Deltapsi) is the key driving force to convert
      ion translocation through the F(0) motor components into torque. The resulting
      rotation elicits conformational changes at the catalytic sites of the peripheral
      F(1) domain which are instrumental for ATP synthesis. Alkaliphilic bacteria also
      face the challenge of synthesizing ATP at a low electrochemical potential, but
      for entirely different reasons. Here, the low potential is not the result of
      insufficient energy input from substrate degradation, but of an inverse pH
      gradient. This is a consequence of the high environmental pH where these bacteria
      grow and the necessity to keep the intracellular pH in the neutral range. In
      spite of this unfavorable bioenergetic condition, ATP synthesis in alkaliphilic
      bacteria is coupled to the proton motive force (DeltamuH(+)) and not to the much
      higher sodium motive force (DeltamuNa(+)). A peculiar feature of the ATP
      synthases of alkaliphiles is the specific inhibition of their ATP hydrolysis
      activity. This inhibition appears to be an essential strategy for survival at
      high external pH: if the enzyme were to operate as an ATPase, protons would be
      pumped outwards to counteract the low DeltamuH(+), thus wasting valuable ATP and
      compromising acidification of the cytoplasm at alkaline pH.

PMID- 15518832
TI  - Dissimilatory Fe(III) and Mn(IV) reduction.
AB  - Dissimilatory Fe(III) and Mn(IV) reduction has an important influence on the
      geochemistry of modern environments, and Fe(III)-reducing microorganisms, most
      notably those in the Geobacteraceae family, can play an important role in the
      bioremediation of subsurface environments contaminated with organic or metal
      contaminants. Microorganisms with the capacity to conserve energy from Fe(III)
      and Mn(IV) reduction are phylogenetically dispersed throughout the Bacteria and
      Archaea. The ability to oxidize hydrogen with the reduction of Fe(III) is a
      highly conserved characteristic of hyperthermophilic microorganisms and one
      Fe(III)-reducing Archaea grows at the highest temperature yet recorded for any
      organism. Fe(III)- and Mn(IV)-reducing microorganisms have the ability to oxidize
      a wide variety of organic compounds, often completely to carbon dioxide. Typical
      alternative electron acceptors for Fe(III) reducers include oxygen, nitrate,
      U(VI) and electrodes. Unlike other commonly considered electron acceptors,
      Fe(III) and Mn(IV) oxides, the most prevalent form of Fe(III) and Mn(IV) in most
      environments, are insoluble. Thus, Fe(III)- and Mn(IV)-reducing microorganisms
      face the dilemma of how to transfer electrons derived from central metabolism
      onto an insoluble, extracellular electron acceptor. Although microbiological and
      geochemical evidence suggests that Fe(III) reduction may have been the first form
      of microbial respiration, the capacity for Fe(III) reduction appears to have
      evolved several times as phylogenetically distinct Fe(III) reducers have
      different mechanisms for Fe(III) reduction. Geobacter species, which are
      representative of the family of Fe(III) reducers that predominate in a wide
      diversity of sedimentary environments, require direct contact with Fe(III) oxides
      in order to reduce them. In contrast, Shewanella and Geothrix species produce
      chelators that solubilize Fe(III) and release electron-shuttling compounds that
      transfer electrons from the cell surface to the surface of Fe(III) oxides not in
      direct contact with the cells. Electron transfer from the inner membrane to the
      outer membrane in Geobacter and Shewanella species appears to involve an electron
      transport chain of inner-membrane, periplasmic, and outer-membrane c-type
      cytochromes, but the cytochromes involved in these processes in the two organisms
      are different. In addition, Geobacter species specifically express flagella and
      pili during growth on Fe(III) and Mn(IV) oxides and are chemotactic to Fe(II) and
      Mn(II), which may lead Geobacter species to the oxides under anoxic conditions.
      The physiological characteristics of Geobacter species appear to explain why they
      have consistently been found to be the predominant Fe(III)- and Mn(IV)-reducing
      microorganisms in a variety of sedimentary environments. In comparison with other
      respiratory processes, the study of Fe(III) and Mn(IV) reduction is in its
      infancy, but genome-enabled approaches are rapidly advancing our understanding of
      this environmentally significant physiology.

PMID- 15518835
TI  - Treatment of multilevel cervical fusion with cages.
AB  - BACKGROUND: Multilevel cervical discectomy usually requires plate and screw
      fixation for maintaining the spinal curvature, and increasing the graft fusion
      rate. However, the use of plate and screw fixation may cause a few complications,
      such as screw breakage, screw pullout, esophagus perforation, and cord or nerve
      root injury. In this study, we try to use cages to replace plate function in
      multilevel cervical fusion. METHODS: From January 1997 to June 2001, there were
      180 consecutive cases of multilevel cervical degenerative disease. We randomized
      them into three groups: Group A (60 patients) underwent anterior discectomy and
      polyetheretherketone (PEEK) fusion, Group B (50 patients) underwent anterior
      discectomy, autogenous iliac crest graft (AICG) fusion and plate fixation, and
      Group C (70 patients) underwent anterior discectomy and AICG only. X-ray of
      cervical spine was taken every 3 months until fusion was complete. Spinal
      curvature was measured by lateral view of X-ray. The functional and working
      status were evaluated by Prolo scale. Blood loss and operation time were
      recorded, respectively. RESULTS: The total complication rates were 3.3%, 16%, and
      54.3% in Groups A, B, and C respectively. The graft complications were evaluated
      by radiographic findings (graft collapse, nonunion, or dislodged graft). However,
      only 37.1% of patients (13/35) with graft complications had clinical symptoms
      (severe neck pain, radicular pain, or neurologic deficits). The fusion rate was
      better, and the time to fusion was sooner in Groups A and B than Group C, p <
      0.001 (chi(2) test). PEEK cage is statistically better than plating group in
      total complications, p < 0.05. Graft collapse and nonunion were the major graft
      complications in Group C (AICG without plating). Screw pullout, and screw
      breakage were the main causes of plating complication. Blood loss was minimum in
      Group A, p < 0.05. Spinal lordosis increased by a mean of 4.61 +/- 2.93 mm and
      1.68 +/- 5.02 mm in Groups A and B, respectively, but spinal kyphosis increased
      by a mean of -2.09 +/- 4.77 mm in Group C. Group A had a statistically better
      Prolo scale than Group C, p < 0.0001. CONCLUSIONS: Both PEEK cage without plating
      and AICG with plating are good methods for interbody fusion in multilevel
      cervical degenerative diseases. They increase spinal lordosis and graft fusion
      rate, and cause fewer surgical complications. However, PEEK cage is preferred in
      our study for multilevel fusion, because it has the fewest complication rates and
      the least amount of blood loss.

PMID- 15518839
TI  - A new epineural nerve repair technique with external metallic circle.
AB  - BACKGROUND: Despite the existence of various nerve coaptation techniques,
      functional results of nerve repair are still inadequate. Potential benefits of
      developing modified coaptation techniques cannot be disregarded. METHODS: The
      authors report a new coaptation technique in which the epineural sutures were
      performed with an external metallic circle to increase the coaptation surface.
      The sciatic nerves of 30 male Wistar albino rats were used in the study. RESULTS:
      The mean Sciatic Function Index values in external metallic circle repair (n:11)
      and conventional epineural repair (n:10) groups were -42.35 +/- 22.95 and -69.34
      +/- 17.96, respectively (p = 0.020). Electrophysiological studies revealed that
      the duration of compound muscle action potentials (CMAP) was (p = 0,012) shorter
      in conventional nerve repair group than it was in external metallic nerve repair.
      When external metallic circle repair and conventional epineural repair groups
      were examined for distal nerve segments, there were significant findings for the
      diameter of axons (p = 0.005), diameter of nerves (p = 0.000), and for G ratios
      (p = 0.000). The mean intraepineural cross sectional areas of external metallic
      circle repair and conventional epineural repair groups were 3.57 +/- 0.21 and
      2.92 +/- 0.23 mm(2), respectively (p = 0.000). CONCLUSION: The external metallic
      circle repair technique enhances nerve regeneration by enabling a larger
      sprouting and contact area for nerve fibers.

PMID- 15518841
TI  - Apoptosis, vascularity, and proliferation in primary central nervous system
      lymphomas (PCNSL): a histopathological study.
AB  - BACKGROUND: In the present study apoptosis, vascularity, and proliferation were
      quantitatively analyzed with immunohistopathological techniques in primary
      central nervous system lymphomas (PCNSL). Statistical analysis of these
      parameters was performed to evaluate their possible relationship with the
      unfavorable outcome of this tumor. METHODS: A series of 32 PCNSL patients for a
      total of 33 tumors treated from 1984 to 2000 in the Neurosurgical Department were
      reviewed, and their histologic specimens examined for apoptosis, vascularity, and
      proliferation. RESULTS: Patients were treated with either gross total/subtotal
      tumor removal or stereotactic biopsy. Vascularity was studied by means of FVIII
      staining, proliferative index with Ki-67 staining, and apoptosis with the TUNEL
      technique. Most tumors could be classified as immunoblastic or centroblastic B
      Cell NHL. Mean Mib-1 Labeling Index was 35.34% (5-80), blood vessel density of
      40.8 per 10 high power fields. Apoptotic cells were zero or less than 8 cells per
      10 high power fields. CONCLUSION: No statistically significant correlation
      between survival and histopathological parameters could be shown. However, the
      apoptosis index was found to be negatively correlated with proliferative index
      and may account for a more aggressive clinical course of PCNSL.

PMID- 15518846
TI  - Experimental microaneurysms in rats: I. Model for induction.
AB  - BACKGROUND: Small aneurysms (lesser than 2 mm) in humans called sessile, baby
      aneurysms, or microaneurysms, generally are not able to be clipped or to be coil
      packed through endovascular route. Among the modalities of treatment that have
      been used for treating microaneurysms, bipolar coagulation and wrapping of the
      lesion are outstanding. Nevertheless, demonstration of the efficacy of these
      treatments is difficult because most reported experimental models for inducting
      aneurysms are complex and difficult to be reproduced. This study aimed to develop
      a simple and reproducible model for inducing microaneurysms. METHODS:
      Microaneurysms were induced using a mechanical lesion of the bifurcation of the
      aorta in 72 rats. Three groups of 10 animals were sacrificed 7, 14, and 21 days
      after the lesion and 2 groups (35 and 7 animals) after 30 days. The aortic
      bifurcation was macro/microscopically analyzed in the first 4 groups and a
      resistance test was applied in the fifth group. RESULTS: Microaneurysms occurred
      in 77.8% of cases. Microscopically, degenerative changes were observed in the
      intima, media, and adventitia and in the internal elastic lamina. The bursting
      pressure ranged from 368 to 1,472 mm Hg during the resistance test in the fifth
      group. CONCLUSIONS: The presented model of experimental microaneurysm induction
      is simple, reproducible and gives a high rate of positivity.

PMID- 15518843
TI  - Trigeminal neuralgia: what are the important factors for good operative outcomes
      with microvascular decompression.
AB  - BACKGROUND: Microvascular decompression has been widely used as the first choice
      in treating trigeminal neuralgia, but in a few patients, facial pain cannot be
      effectively controlled by microvascular decompression. We sought to clarify the
      important factors for good operative outcomes. METHODS: We reviewed 62 patients
      with trigeminal neuralgia treated by microvascular decompression during the
      period 2000 through 2002, including clinical presentation, operative findings,
      techniques, and outcomes. Neurovascular conflicts were divided into single
      contact, contact and indentation, single adhesion, adhesion and indentation, and
      trigeminal nerve atrophy. Operative outcomes were graded into immediate
      postoperative complete pain relief (excellent), delayed postoperative complete
      pain relief (better), significant pain relief (good), and no response to
      microvascular decompression (poor). RESULTS: All patients' presentations were
      typical at the time of pain onset, but the symptom in 17 patients changed to
      atypical before surgery. During operation, single contact and single adhesion was
      found in 14 patients and 15 patients, respectively; contact or adhesion in
      combination with indentation was found in 7 patients and 18 patients,
      respectively; atrophy occurred in 8 patients. Postoperatively, immediate and
      delayed complete pain relief was achieved in 32 (51.6%) patients and 17 (27.4%)
      patients, respectively; 11(17.7%) patients got significant pain relief; and 2
      patients showed no response. The overall rate of complete pain relief in patients
      with shorter duration, typical presentation, artery compression and complete
      decompression was higher than that in patients with longer duration, atypical
      presentation, venous compression, and incomplete decompression. CONCLUSIONS:
      Shorter duration, typical presentation, single artery compression, and complete
      decompression are the positive factors for better operative outcomes with
      microvascular decompression. Worse outcomes are usually related to venous
      compression, longer duration, and atypical presentation.

PMID- 15518847
TI  - Experimental microaneurysms in rats: II. Comparison between cotton wrapping and
      microbipolar coagulation.
AB  - BACKGROUND: Microsurgical aneurysm clipping is considered the best treatment for
      intracranial aneurysms, but often it cannot be used for microaneurysms. These
      aneurysms may require different type of treatment like bipolar coagulation or
      wrapping to reinforce the aneurysm wall, but these treatments have no
      experimentally proven efficacy. In this study the authors analyze the efficacy of
      2 methods of treatment to prevent rupture of experimentally induced
      microaneurysms. METHODS: Microaneurysms were induced using mechanical compression
      of the wall of the aortic bifurcation in 60 rats. The animals were divided in
      three groups according to aneurysm treatment: Group 1-aneurysms treated using
      microbipolar coagulation; Group 2-aneurysms wrapped with cotton, and Group 3-no
      treatment. Four weeks after the treatment, the resistance of the microaneurysm
      was tested applying intraluminal hyperpressure (up to 2,427 mm Hg). After that,
      the vessels were microscopically analyzed. RESULTS: No rupture of the aneurysms
      was observed in Group 2 and all aneurysms ruptured in Groups 1 and 3 during the
      resistance test. Comparison between the mean bursting pressure of Groups 1 and 3
      showed no significant difference (Student's t test, p > 0.05). The probability of
      rupture of the microaneurysms was significantly different between Groups 1 and 2,
      favoring Group 2 (Fisher exact test, p < 0.001). CONCLUSIONS: Wrapping of
      experimental microaneurysms with cotton was effective to protect aneurysm rupture
      under hyperpressure; and there was no protection using microbipolar coagulation.

PMID- 15518850
TI  - Early external decompressive craniectomy with duroplasty improves functional
      recovery in patients with massive hemispheric embolic infarction: timing and
      indication of decompressive surgery for malignant cerebral infarction.
AB  - BACKGROUND: Extensive cerebral hemispheric infarction associated with massive
      brain swelling is known as malignant infarction because of the rapid clinical
      deterioration and mortality as high as 80% unless appropriate treatment is
      performed. Decompressive craniectomy is an effective treatment, but patient
      selection, timing, functional recovery, and complications remain unclear.
      METHODS: Seventy-one patients with massive embolic hemispheric infarctions
      (infarct volume >200 cm(3)) associated with brain swelling were retrospectively
      divided into 3 groups according to the therapeutic modalities: 21 patients were
      treated conservatively (conservative group); 50 patients were treated by external
      decompressive craniectomy with duroplasty in 2 groups; 29 patients treated after
      the appearance of clinical and radiologic findings of brain herniation (late
      surgery group); and 21 patients treated before the onset of brain herniation
      (early surgery group). RESULTS: The mortality at 1 and 6 months in the
      conservative group were 61.9% and 71.4%, respectively. The mortality at 1 and 6
      months in the late surgery group were significantly improved to 17.2% and 27.6%,
      respectively, (p < 0.01) and in the early surgery group were further improved to
      4.8% and 19.1%, respectively. The functional recovery of the patients was
      estimated by the Glasgow Outcome Scale (GOS) and Barthel Index (BI) at 6 months
      after the ictus. The GOS scores of the early surgery group were significantly
      better than that of the late surgery group (p < 0.05). The mean BI score of the
      survivors in the late surgery group (26.9 +/- 30.4) was not significantly
      different from that of the conservative group (28.3 +/- 42.2), but was
      significantly improved in the early surgery group (52.9 +/- 34.2) compared with
      the late surgery group (p < 0.05). CONCLUSIONS: Early decompressive craniectomy
      with duroplasty before the onset of brain herniation should be performed to
      achieve satisfactory functional recovery if the infarct volume of the hemispheric
      cerebral infarction is more than 200 cm(3) and computed tomography on the second
      day after the ictus shows mass effect.

PMID- 15518852
TI  - Successful management of post-traumatic C7-T1 spondyloptosis with uninstrumented
      ventral surgery.
AB  - BACKGROUND: Total spondyloptosis of the cervical spine is a very rare injury. The
      authors describe an unusual case of post-traumatic total spondyloptosis of the
      cervical spine at C7-T1 level. CASE DESCRIPTION: A 40-year-old man presented with
      weakness of all four limbs, impaired sensations in all limbs and neck pain after
      a fall. A magnetic resonance image (MRI) of the cervical spine revealed a total
      spondyloptosis at C7-T1 level. He was managed successfully with ventral
      decompression and uninstrumented in situ fusion. The patient had a good
      neurologic outcome. CONCLUSION: Selected patients with spondyloptosis of the
      cervical spine can be successfully managed with uninstrumented ventral surgery.

PMID- 15518853
TI  - Gamma knife radiosurgery for trigeminal schwannomas.
AB  - BACKGROUND: Trigeminal schwannomas are uncommon tumors that may be
      microsurgically removed in selected cases, albeit with significant risk for new
      neurological morbidity. We evaluated the role of stereotactic radiosurgery as an
      alternative for patients with newly diagnosed or residual trigeminal schwannomas.
      METHODS: The records of 23 patients who underwent radiosurgery for trigeminal
      schwannoma were reviewed. The most frequent presenting symptoms were facial
      numbness (11 patients), diplopia (6 patients), and facial pain (3 patients). One
      patient presented with partial complex seizures as the first symptom. Twelve
      patients had undergone one or more prior resections. Eleven underwent
      radiosurgery on the basis of imaging diagnosis only. The mean tumor volume was
      4.5 mL (range 0.46-11.2 cc). Radiosurgery was performed using a median marginal
      dose of 15 Gy (range, 13-20 Gy). RESULTS: At a median imaging follow-up of 40
      months (range, 12-146), 20 of 22 evaluable patients (91%) had tumor growth
      control (regression in 15 and no further tumor growth in 5). One 80-year-old
      patient died of unrelated cause 4 months after radiosurgery. Two patients with
      enlarged tumors were treated effectively with repeat radiosurgery. Twelve of 23
      patients (52%) reported improvement and 9 (39%) had no change in their symptoms.
      Two patients noted new neurological complaints (transient facial weakness in 1
      patient and worsening of the preradiosurgery facial numbness in another patient).
      CONCLUSIONS: Radiosurgery is an effective minimally invasive management option
      for patients with residual or newly diagnosed trigeminal schwannomas.

PMID- 15518856
TI  - Solitary Langerhans-cell histiocytosis of the clivus and sphenoid sinus with
      parasellar and petrous extensions: case report and a review of literature.
AB  - BACKGROUND: In Langerhans-cell histiocytosis, there occurs an uncontrolled clonal
      proliferation of dendritic cells that have Langerhans cell like characteristics.
      In this report, a unique case of a solitary, skull base Langerhans-cell
      histiocytosis (LCH) is described. CASE DESCRIPTION: A 15-year-old boy presented
      with raised intracranial pressure, decreased visual acuity, bilateral abducent
      nerve palsy, and 25% hypoesthesia in all three divisions of the right trigeminal
      nerve. He had normal strength but with a left-sided upper and lower limb
      hypertonia and hyper-reflexia and an upgoing plantar reflex. The magnetic
      resonance (MR) imaging revealed a heterogeneously iso-to hyperintense lesion of
      the clivus and the sphenoid sinus, extending to the right cavernous sinus to
      encase the right cavernous internal carotid artery segment, and also involving
      the right petrous apex and the extradural space in the prepontine region. The
      lesion was brilliantly enhancing on contrast. An extended frontobasal approach
      was used to excise the lesion. Following surgery, the residual parasellar and the
      right petrous apex tumor was treated with a low dose radiation therapy. At follow
      up after 1.5 years, there was significant clinical improvement and the computed
      tomographic scan showed no residual lesion. CONCLUSION: A review of the
      literature reveals that this is only the second reported case of a spheno-clival
      LCH. An additional feature includes extensions into the parasellar as well as the
      petrous apex regions. Despite the extensive spread, the surgical excision with
      low dose radiation therapy was successful in providing complete resolution of the
      tumor.

PMID- 15518857
TI  - Treatment of giant fusiform aneurysms of the basilar trunk with intra-aneurysmal
      and basilar artery coil embolization.
AB  - OBJECTIVE: The authors report their experience in endovascular treatment of
      basilar artery (BA) trunk aneurysms by intra-aneurysmal and BA occlusion.
      METHODS: Four patients were referred to our hospital from 1995 until 2002 with
      variable clinical presentations and radiologic appearances. All the patients were
      subjected for tolerability to balloon BA occlusion test to verify the collateral
      supply from the posterior communicating arteries. The patients were treated by
      intra-aneurysmal embolization together with basilar artery occlusion. RESULTS:
      All the aneurysms were successfully isolated from the circulation. Transient
      postoperative neurologic deficits were constant findings in all the cases.
      Outcome was finally good for all the patients. CONCLUSIONS: Endovascular
      treatment of complex BA trunk aneurysm by intra-aneurysmal embolization and BA
      occlusion method is a valuable alternative for management and successful
      isolation in patients with good collateral arterial flow.

PMID- 15518860
TI  - Obliteration of a tentorial dural arteriovenous fistula causing spinal cord
      myelopathy using the cranio-orbito zygomatic approach.
AB  - BACKGROUND: Intracranial dural arteriovenous fistulas account for 10 to 15% of
      all intracranial arteriovenous malformations. Tentorial dural arteriovenous
      fistulas with spinal medullary venous drainage causing spinal cord myelopathy are
      very rare, but have been previously described. We describe a case using a cranio
      orbito zygomatic approach with intraoperative angiography for the surgical
      treatment of a tentorial artery dural arteriovenous fistula causing spinal cord
      myelopathy. CASE PRESENTATION: A 42-year-old male presented complaining of a 1
      year history of incoordination and dizziness and a 2-month history of progressive
      myelopathy with bowel and bladder incontinence. The patient had magnetic
      resonance imaging (MRI) performed along with cerebral and spinal angiography that
      revealed a right tentorial artery dural arteriovenous fistula with spinal
      medullary venous involvement down to T11. Angiographic embolization was
      attempted, but selective catheterization was unsuccessful. The patient underwent
      a cranio-orbito zygomatic approach with obliteration of the dural arteriovenous
      fistula. An intraoperative angiogram confirmed complete obliteration of the dural
      arteriovenous fistula. CONCLUSION: Intracranial dural arteriovenous fistulas are
      a rare cause of spinal cord myelopathy. When a patient presents with suspicion of
      spinal dural fistula and negative spinal angiography, an intracranial origin
      should be suspected and a cerebral angiogram performed. Skull base approaches
      along with intraoperative angiography provide an alternative modality for
      obliteration of the dural arteriovenous fistula nidus, thereby eliminating the
      venous congestion and hence the spinal cord ischemia.

PMID- 15518863
TI  - Why medicine, physicians and neuroscience ventures fail.

PMID- 15518865
TI  - Re: Vertebrobasilar junction aneurysms associated fenestration: experience of
      five cases treated with Guglielmi detachable coils. Surg Neurol 2004;61:248-54.

PMID- 15518866
TI  - Re: Biomechanical models to guide the surgical approach in atlantoaxial
      instability. Surg Neurol 2004;62:3.

PMID- 15518867
TI  - Re: The keys to the future of healthcare everywhere. Surg Neurol 2004;61:499-500.

PMID- 15518872
TI  - Plant-associated Pseudomonas populations: molecular biology, DNA dynamics, and
      gene transfer.
AB  - Bacteria of the genus Pseudomonas are usual colonizers of plant leaves, roots,
      and seeds, establishing at relatively high cell densities on plant surfaces,
      where they aggregate and form microcolonies similar to those observed during
      biofilm development on abiotic surfaces. These plant-associated biofilms undergo
      chromosomal rearrangements and are hot spots for conjugative plasmid transfer,
      favored by the close proximity between cells and the constant supply of nutrients
      coming from the plant in the form of exudates or leachates. The molecular
      determinants known to be involved in bacterial colonization of the different
      plant surfaces, and the mechanisms of horizontal gene transfer in plant
      associated Pseudomonas populations are summarized in this review.

PMID- 15518873
TI  - Host controlled plasmid replication: Escherichia coli minichromosomes.
AB  - Escherichia coli minichromosomes are plasmids replicating exclusively from a
      cloned copy of oriC, the chromosomal origin of replication. They are therefore
      subject to the same types of replication control as imposed on the chromosome.
      Unlike natural plasmid replicons, minichromosomes do not adjust their replication
      rate to the cellular copy number and they do not contain information for active
      partitioning at cell division. Analysis of mutant strains where minichromosomes
      cannot be established suggest that their mere existence is dependent on the
      factors that ensure timely once per cell cycle initiation of replication. These
      observations indicate that replication initiation in E. coli is normally
      controlled in such a way that all copies of oriC contained within the cell,
      chromosomal and minichromosomal, are initiated within a fairly short time
      interval of the cell cycle. Furthermore, both replication and segregation of the
      bacterial chromosome seem to be controlled by sequences outside the origin
      itself.

PMID- 15518874
TI  - Transcriptional regulation of pWW0 transfer genes in Pseudomonas putida KT2440.
AB  - The conjugative IncP-9 plasmid pWW0 (TOL) carries transfer genes, many of whose
      functions can be predicted from sequence similarities to the well-studied IncW
      and IncP-1 plasmids, and that are clustered with the replication and maintenance
      genes of the plasmid core. In this study we show that the IncP-9 transfer genes
      are transcribed from at least three promoter regions. The promoters for traA and
      traD act divergently from the region found to encode the origin of transfer,
      oriT. These promoters regulate expression of traA, B, and perhaps traC in one
      direction and traD in the other, all of whose gene products are predicted to be
      involved in relaxasome formation and DNA processing during transfer, and they are
      repressed by TraA. The third promoter region, upstream of mpfR, is responsible
      for transcription of mpfR and mpfA to mpfJ, encoding proteins involved in mating
      pair formation. Transcription from this region is negatively autoregulated by
      MpfR. Thus the pWW0 transfer genes, like those of the IncP-1 plasmids, are
      expressed at all times, but kept in control by a negative feed back loop to limit
      the metabolic burden on the host. Although many of the related mating pair
      formation systems are, as in pWW0, transcribed divergently from an operon for
      replication and/or stable inheritance functions, MpfR is not related to the known
      regulatory proteins of these other transfer systems outside those of the IncP-9
      family and indeed the regulators tend to be specific for each plasmid family.
      This suggests that the general pattern of genetic organisation exhibited by these
      systems has arisen a number of times independently and must therefore be highly
      favourable to plasmid survival and spread.

PMID- 15518875
TI  - The complete nucleotide sequence of the resistance plasmid R478: defining the
      backbone components of incompatibility group H conjugative plasmids through
      comparative genomics.
AB  - Horizontal transfer of resistance determinants amongst bacteria can be achieved
      by conjugative plasmid DNA elements. We have determined the complete 274,762 bp
      sequence of the incompatibility group H (IncH) plasmid R478, originally isolated
      from the Gram negative opportunistic pathogen Serratia marcescens. This self
      transferable extrachromosomal genetic element contains 295 predicted genes, of
      which 144 are highly similar to coding sequences of IncH plasmids R27 and pHCM1.
      The regions of similarity among these three IncH plasmids principally encode core
      plasmid determinants (i.e., replication, partitioning and stability, and
      conjugative transfer) and we conducted a comparative analysis to define the
      minimal IncHI plasmid backbone determinants. No resistance determinants are
      included in the backbone and most of the sequences unique to R478 were contained
      in a large contiguous region between the two transfer regions. These findings
      indicate that plasmid evolution occurs through gene acquisition/loss
      predominantly in regions outside of the core determinants. Furthermore, a modular
      evolution for R478 was signified by the presence of gene neighbors or operons
      that were highly related to sequences from a wide range of chromosomal,
      transposon, and plasmid elements. The conjugative transfer regions are most
      similar to sequences encoded on SXT, Rts1, pCAR1, R391, and pRS241d. The dual
      partitioning modules encoded on R478 resemble numerous sequences; including pMT1,
      pCTX-M3, pCP301, P1, P7, and pB171. R478 also codes for resistance to
      tetracycline (Tn10), chloramphenicol (cat), kanamycin (aphA), mercury (similar to
      Tn21), silver (similar to pMG101), copper (similar to pRJ1004), arsenic (similar
      to pYV), and tellurite (two separate regions similar to IncHI2 ter determinants
      and IncP kla determinants). Other R478-encoded sequences are related to Tn7,
      IS26, tus, mucAB, and hok, where the latter is surrounded by insLKJ, and could
      potentially be involved in post-segregation killing. The similarity to a diverse
      set of bacterial sequences highlights the ability of horizontally transferable
      DNA elements to acquire and disseminate genetic traits through the bacterial gene
      pool.

PMID- 15518876
TI  - Complete nucleotide sequence and structural organization of pPB1, a small
      Lactobacillus plantarum cryptic plasmid that originated by modular exchange.
AB  - A small cryptic plasmid designated pPB1 was isolated from Lactobacillus plantarum
      BIFI-38 and its complete 2899 bp nucleotide sequence was determined. Sequence
      analysis revealed four putative open reading frames. Based on sequence analysis
      two modules could be identified. First, the replication module consisted of a
      sequence coding for a replication protein (RepB) and its corresponding target
      site, and two putative repressor proteins (RepA and RepC). Sequence analysis
      indicated the possible synthesis of an antisense RNA that might regulate RepB
      production. A putative lagging-strand initiation site was also found, suggesting
      that pPB1 replicates via a rolling circle mechanism. The second module of pPB1
      consisted of a sequence coding for a putative mobilization protein and its
      corresponding oriT site. Since the nucleotide sequence of the replication module
      showed 94.5% identity to the similar region on the Leuconostoc lactis plasmid
      pCI411, and the nucleotide sequence of the mobilization module had 97.5% identity
      to L. plantarum plasmid pLB4, it is concluded that pPB1 originated by modular
      exchange between two such plasmids by homologous recombination. Putative
      recombination sites where crossover might have taken place were also identified.

PMID- 15518877
TI  - Plasmid transfer in bacilli by a self-transmissible plasmid p19 from a Bacillus
      subtilis soil strain.
AB  - The cryptic 95-kb plasmid p19 of the Bacillus subtilis 19 soil strain promotes
      the transfer of a small kanamycin resistance plasmid pUB110. To facilitate direct
      selection for p19 transfer, a plasmid derivative carrying the chloramphenicol
      resistance gene was constructed. The frequency of transfer of the large plasmid
      between cells of B. subtilis 19 approached 100% but was more than two orders of
      magnitude lower when the strain B. subtilis 168 was a recipient. However, when
      the restriction-deficient strain B. subtilis 168 was a recipient, the transfer
      efficiency was almost completely recovered. The effectiveness of pUB110
      mobilization was virtually not altered in all these cases. pC194 was not
      mobilized by p19. The kinetics of p19 conjugative transfer is also presented.

PMID- 15518878
TI  - Sequence analysis and characterization of sulfonamide resistance plasmid pRF-1
      from Salmonella enterica serovar Choleraesuis.
AB  - The nucleotide sequence of a small plasmid, designated pRF-1, isolated from
      Salmonella enterica serovar Choleraesuis, was determined. We identified seven
      open reading frames (ORFs) encoded by 6066 nucleotides with a total G + C content
      of 53.6%. Analysis of the complete nucleotide sequence revealed a replicon of pRF
      1 to have high similarity to the p15A origin of replication, with a possible cer
      like region. ORF1, which is composed of 816 nucleotides, shows a high degree of
      similarity to dihydropteroate synthetase encoded by the sulII gene from plasmids
      in several enteropathogenic bacteria, which functions as the sulfonamide
      resistance determinant. In fact, Salmonella and Escherichia coli strains carrying
      pRF-1 were found to show strong resistance to sulfathiazole, suggesting that orf1
      is a functional gene. Four of seven ORFs were found to encode putative proteins
      of unknown function.

PMID- 15518879
TI  - Sequence analysis of pDN571, a plasmid encoding novel bacteriocin production in M
      type 57 Streptococcus pyogenes.
AB  - Production of the novel bacteriocin streptococcin A-M57 (SA-M57) by Streptococcus
      pyogenes strains of M-protein type 57 is plasmid-associated. Plasmid pDN571
      (3351bp) harbored by S. pyogenes 71-724, the prototype M-type 57 strain, has been
      completely sequenced and contains three putative open reading frames (repA,
      scnM57 and ORF3). In addition, the double-strand and single-strand (SSO) origins
      of replication were identified. Analysis of the replication-associated genetic
      elements places pDN571 in the ubiquitous pC194/pUB110 family of rolling-circle
      plasmids. The SSO of pDN571 is of the ssoA type. SA-M57 (encoded by scnM57) is
      synthesized as a secreted 179-amino acid polypeptide with a 27-residue secretion
      signal peptide and has no homology to proteins of known function.

PMID- 15518880
TI  - Organization of the horizontally transferred pheBA operon and its adjacent genes
      in the genomes of eight indigenous Pseudomonas strains.
AB  - Horizontal transfer of genes encoding phenol degradation (pheBA) in the
      environment has been previously described. Complete or partial phe-operon was
      redetected in plasmids of several indigenous Pseudomonas strains isolated from
      the river water. The sequences of up- and downstream regions of the acquired phe
      DNA in eight different plasmids were analyzed. In all cases, miniature
      insertional elements or putative transposase genes were found suggesting
      transposase dependent pheBA integration into plasmids. In three cases, an open
      reading frame encoding homologue to the transcription regulator protein (CatR) of
      the pheBA operon was determined.

PMID- 15518881
TI  - Structural insights into the regulation and the activation mechanism of mammalian
      guanylyl cyclases.
AB  - Guanylyl cyclases (GC) are proteins that are essential for the production of the
      second messenger cyclic guanosine monophosphate (cGMP). Mammalian GC have
      attracted considerable interest due to their roles in important physiological
      processes such as vasodilation, vision, and bone growth. In addition, their link
      to disease and concomitant pharmaceutical potential have made these cyclases a
      long standing target for probing their intriguing mechanism of activation with
      the aim of drug development. The vasodilatory drugs nitroglycerin and nesiritide
      act through (different) GC pathways and have both been shown to provide
      beneficial relief for congestive heart failure patients. New structural insights
      are recently emerging on the activation mechanism and regulation of these
      receptors. The aim of this review is to discuss the interesting differences and
      similarities between members of the soluble and membrane bound GC in detail and
      put these in context with the structural knowledge that is available to date.
      These efforts contribute to an enhanced understanding of the GC and will likely
      lead to an increased success in structure-based therapeutic intervention.

PMID- 15518882
TI  - mda-9/syntenin: recent insights into a novel cell signaling and metastasis
      associated gene.
AB  - PDZ (an acronym representing three proteins--postsynaptic density protein
      PSD95/SAP90, drosophila tumor suppressor DLGA, and tight junction protein ZO-1)
      domain containing proteins are adapter proteins that play indispensable roles in
      regulating cell growth, development, and differentiation, predominantly through
      their capacity to serve as central organizers of protein complexes at the plasma
      membrane. A recently identified member of this protein family is melanoma
      differentiation associated gene-9 (mda-9), also known as syntenin, which was
      first identified as a gene down-regulated during human melanoma differentiation
      as mda-9 and subsequently recognized as an interacting partner of the cell
      surface heparan sulfate syndecans, syntenin. Interest in mda-9/syntenin is
      intensifying because of its involvement in organization of protein complexes in
      the plasma membranes, regulation of B cell development, intracellular trafficking
      and cell surface targeting, cancer metastasis, synaptic transmission, and axonal
      outgrowth. In this review, we discuss the identification, structure and function
      of mda-9/syntenin and delineate future studies to address its role in regulating
      key physiological and pathological processes.

PMID- 15518883
TI  - Anandamide transport.
AB  - N-Arachidonylethanolamine (anandamide) is an endogenous agonist of the
      cannabinoid CB1 and CB2 receptors and displays many of the same receptor-mediated
      physiological effects as delta9-tetrahydrocannabinol (delta9-THC), the active
      component of marijuana. As with any neurotransmitter, there must be tight control
      of anandamide receptor-mediated signaling and a means of rapid removal of the
      molecule from the system. Thus, the process by which anandamide is transported
      into the cell for metabolism has been a topic of much interest and has been
      implicated as a potential drug target in the treatment of several disease states
      that are reported to have an association with the endocannabinoid system. In this
      review, we will discuss the current models proposed for the mechanism of
      anandamide transport, the progress that has been made in the development of
      compounds that specifically inhibit anandamide transport, the observed effects of
      anandamide transport inhibition in vivo, and finally, potential therapeutic
      applications of compounds that inhibit anandamide transport.

PMID- 15518884
TI  - Uroguanylin and guanylin peptides: pharmacology and experimental therapeutics.
AB  - Guanylin, uroguanylin, and the bacterial heat-stable enterotoxin (ST) peptides
      comprise a new family of cyclic guanosine 3'-5' monophosphate (cGMP)-regulating
      agonists. The discovery of guanylin and uroguanylin peptides stems from studies
      of cellular mechanisms underlying a form of secretory diarrhea caused by enteric
      bacteria. Guanylin, uroguanylin, and microbial ST peptides activate a common
      apical membrane receptor-guanylate cyclase (R-GC) that elicits large increases in
      the intestinal secretion of chloride and bicarbonate via the intracellular second
      messenger, cGMP. Guanylin and uroguanylin were isolated from rat jejunum and
      opossum urine, respectively. These peptides are endogenous peptide hormones that
      physiologically regulate R-GC signaling proteins in target cells. Physiological
      roles for these peptides include the regulation of epithelial cell balance in the
      intestinal epithelium and modulation of sodium balance through actions in the
      kidney. The guanylin-uroguanylin-ST peptides are candidate therapeutic agents
      targeting receptors in the intestine, kidney, and other epithelia. For example,
      uroguanylin has anti-tumor actions in an animal model for human colon cancer. The
      ST peptides can be used as diagnostic agents to detect secondary colon cancers by
      single photon-emitting computed tomography (SPECT) imaging, thus localizing
      metastatic forms of colon cancer. Other examples of potential therapeutic
      applications for the guanylin family of cGMP-regulating agonists are: (1) the
      irritable bowel syndrome (IBS) with constipation, (2) salt-dependent forms of
      high blood pressure, (3) liver regeneration and repair, and (4) respiratory
      diseases such as asthma. Competitive pharmacological antagonists of bacterial ST
      peptides offer a means for treating the diarrhea caused by ST-secreting strains
      of enteric bacteria.

PMID- 15518886
TI  - Compound exocytosis of secretory granules containing salivary chromogranin A in
      granular duct cells in rat submandibular gland: the last study in collaboration
      with the late Professor Noboru Yanaihara at Yanaihara Institute.
AB  - Chromogranin A (CgA) is a member of a family of chromogranins, which are co
      stored and co-released with adrenaline and noradrenalin (NAd) in the adrenal
      medulla in response to stimulation of the splanchnic nerve. Double
      immunohistochemical staining is carried out by use of antibodies against CgA and
      1,4,5-trisphosphate receptor type 2 (IP3R2) on the same sections prepared from
      the isolated and perfused submandibulllar gland of rat. In the control sections
      prepared from resting state, an intense IP3R2 immunoreactivity (IR) appeared
      preferentially at the apical pole of subpopulation of the granulated duct cells,
      in which CgA-like IR distributed throughout the cytoplasm. Electron-micrograph
      showed that the granular cells in the resting state stored numerous membrane
      bound granules in the apical cytoplasm. Stimulation with 1 microM NAd caused
      rapid immediate increase in secretory responses. Sections prepared from the gland
      at the peak of secretory responses exhibited that, in the granular duct cells,
      the apically converge IP3R2 IR became diffuse and indistinguishable, and that the
      apical half of the cells was occupied, indicating that mobilization of Ca2+ from
      the IP3-sensitive pool may preferentially be involved in the secretory responses
      to alpha-adrenergic agonist.

PMID- 15518887
TI  - Neural-restrictive silencers in the regulatory mechanism of pituitary adenylate
      cyclase-activating polypeptide gene expression.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is known as a
      pleiotropic neuropeptide and is present abundantly in central nervous system.
      During a detailed analysis of the 5'-flanking region of the mouse PACAP gene, we
      found and characterized two negative regulatory elements, which are homologous to
      the neural-restrictive silencer element, and are termed neural-restrictive
      silencer-like elements 1 and 2 (NRSLE1 and NRSLE2). Their sequence and position
      were significantly conserved among mouse, human, and rat PACAP genes. In the
      electrophoretic mobility shift assay (EMSA) with nuclear extracts of Swiss-3T3
      cells and individual oligonucleotide probes for NRSLE1 and NRSLE2, a specific
      complex was observed to have the same migration as compared with the NRSE probe
      of rat type II sodium channel gene (NaII). Furthermore, these complexes were
      efficiently competed by the unlabeled NaII probe. In the luciferase reporter
      assay, the reporter gene constructs containing NRSLEs, driven by heterologous
      SV40 promoter, exhibited repression of luciferase activity almost equal to basal
      level in Swiss-3T3 cells. In contrast, the repression was not observed in
      differentiated PC12 cells with NGF. These results suggested that the neural
      restrictive silencer system might be involved in the regulatory mechanism of
      neuron-specific PACAP gene expression.

PMID- 15518888
TI  - Transcriptome of pituitary adenylate cyclase-activating polypeptide
      differentiated PC12 cells.
AB  - Addition of pituitary adenylate cyclase-activating polypeptide (PACAP) into the
      cultured PC12 cells secreted dopamine and promoted neurite outgrowth of the
      cells, indicating cell differentiation. To characterize the PACAP-differentiated
      PC12 cell transcriptome, we applied DNA macroarray techniques, using Atlas Rat
      1.2 Array membranes (BD Biosciences Clontech) that have 1176 cDNA. RNA samples
      were harvested from PC12 cells before and at a time of 6 h treatment with 1 nM
      PACAP, when neuritogenesis was remarkably observed under the condition used.
      Several genes regulated by PACAP have been associated with neuritogenesis (i.e.
      villin 2 and tissue plasminogen activator) or cell growth/differentiation (i.e.
      cyclin or ornitine decarboxylase). Also, cytoskeleton proteins such as actin or
      tubulin were up-regulated for cell morphology remodeling. A message of vehicle
      trafficking molecule (synaptotagmin IV) was more remarkably increased (3.95-6.85
      fold). Signaling molecules such as small G proteins (rab12, rab16, or ral),
      IkappaB, or STAT3 were altered by PACAP. It is noteworthy that PACAP inhibited
      the expression of galanin receptor 2, whose ligand was shown to inhibit tyrosine
      hydroxylase activity. Thus, in this study the transcriptome of PACAP
      differentiated PC12 was established, leading to the elucidation of the molecular
      mechanism of neuritogenesis by the neuropeptide.

PMID- 15518889
TI  - Development of the circadian melatonin rhythm and the effect of PACAP on
      melatonin release in the embryonic chicken pineal gland. An in vitro study.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) has been shown to
      participate in modulation of circadian rhythm and to stimulate melatonin (MT)
      secretion in both the rat and chicken pineal glands. In contrast to mammals, the
      main regulator of circadian rhythm in birds is the pineal gland, which begins its
      rhythmic MT production already during embryonic life. In the present study, we
      investigated the development of MT secretion in explanted embryonic chicken
      pineals and their responsiveness to PACAP in a perifusion system. Our results
      show that: (1) the circadian clock and/or the intracellular signal transduction
      system connecting the clock to MT synthesizing apparatus develop between the
      embryonic days 16-18 (E16-18), even in vitro. (2) Exposure of the embryonic
      chicken pineal gland to PACAP induces transitory increase in MT secretion but
      does not induce visible phase shift in the circadian rhythm. (3) Cyclic AMP
      (cAMP) efflux also responds to PACAP at or before day E13 in embryonic chicken
      pineal gland in vitro.

PMID- 15518890
TI  - Expression of mRNAs for PACAP and its receptor in human neuroblastomas and their
      relationship to catecholamine synthesis.
AB  - PURPOSE: Pituitary adenylate cyclase-activating polypeptide (PACAP), a member of
      the secretin/glucagon/vasoactive intestinal peptide family, induces the
      expression of catecholamine-synthesizing enzymes in adrenal medullary cells. In
      addition, PACAP and its receptor have been detected in human neuroblastoma
      tissues and cell lines, though it is not yet known whether PACAP enhances the
      expression of genes encoding catecholamine-synthesizing enzymes. To address this
      question, we analyzed PACAP, PACAP receptor and tyrosine hydroxylase (TH) mRNAs
      in neuroblastomas. METHODS: The levels of mRNA for PACAP and vasoactive
      intestinal peptide (VIP), as well as their receptors and the mRNA for TH were
      measured by RT-PCR or real-time PCR analysis. RESULTS: VPAC1R mRNA was detected
      in all of 16 tissues and 3 cell lines that were examined, while VPAC2R mRNA was
      detected in 5 of 16 (31%) tissue and 2 of 3 cell lines. PAC1R mRNA was detected
      in 6 out of 16 (38%) tissues and none of 3 cell lines. mRNA expression of PACAP
      and TH were detected in many tissues (10/16 and 16/16, respectively). However,
      neither in tissues nor cell lines did PACAP mRNA expression correlate with TH
      mRNA expression. CONCLUSION: Our findings suggest that PACAP is not involved in
      the regulation of expression of TH in neuroblastomas.

PMID- 15518891
TI  - Differential regulation of activity-dependent neuroprotective protein in rat
      astrocytes by VIP and PACAP.
AB  - Activity-dependent neuroprotective protein (ADNP) was shown to be a vasoactive
      intestinal peptide (VIP) responsive gene in astrocytes derived from the cerebral
      cortex of newborn rats. The present study was set out to identify VIP receptors
      that are associated with increases in ADNP expression in developing astrocytes.
      Using VIP analogues specific for the VPAC1 and the VPAC2 receptors, it was
      discovered that VIP induced changes in ADNP expression in astrocytes via the
      VPAC2 receptor. The constitutive synthesis of ADNP and VPAC2 was shown to be age
      dependent and increased as the astrocyte culture developed. Pituitary adenylate
      cyclase-activating polypeptide (PACAP) also induced changes in ADNP expression.
      The apparent changes induced by VIP and PACAP on ADNP expression were
      developmentally dependent, and while stimulating expression in young astrocytes,
      an inhibition was demonstrated in older cultures. In conclusion, VIP, PACAP and
      the VPAC2 receptor may all contribute to the regulation of ADNP gene expression
      in the developing astrocyte.

PMID- 15518892
TI  - Pituitary adenylate cyclase-activating polypeptide inhibits caspase-3 activity
      but does not protect cerebellar granule neurons against beta-amyloid (25-35)
      induced apoptosis.
AB  - The beta-amyloid (Abeta) peptide Abeta25-35 provokes apoptosis of cerebellar
      granule cells through activation of caspase-3 while the neuropeptide pituitary
      adenylate cyclase-activating polypeptide (PACAP) promotes granule cell survival
      by inhibiting caspase-3 activation through the intrinsic apoptotic pathway. The
      aim of the present study was to determine whether PACAP could prevent Abeta25-35
      neurotoxicity by inhibiting caspase-3 activity. A 24-h exposure of cultured
      cerebellar granule cells to Abeta25-35 induced shrinkage of cell bodies, neurite
      retraction and alteration of mitochondrial activity. Administration of graded
      concentrations (10-80 microM) of Abeta25-35 induced a dose-related decrease of
      the number of living cells, and the neurotoxic effect was highly significant
      after a 24-h exposure to 80 microM Abeta25-35. Exposure of cerebellar granule
      cells to Abeta25-35 markedly enhanced caspase-3 but not caspase-9 activity. Co
      incubation with 1 microM PACAP significantly reduced Abeta25-35-evoked caspase-3
      activation. In contrast, PACAP did not prevent the deleterious effects of Abeta25
      35 on mitochondrial potential and granule cell survival. Taken together, these
      data suggest that caspase-3 activation is not the main pathway activated by
      Abeta25-35 that leads to granule cell death. The results also demonstrate that
      PACAP cannot be considered as a potent neuroprotective factor against Abeta25-35
      induced apoptosis in cerebellar granule neurons.

PMID- 15518893
TI  - Effects of PACAP on in vitro and in vivo neuronal cell death, platelet
      aggregation, and production of reactive oxygen radicals.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) exerts neuroprotective
      effects in various in vitro and in vivo models of cerebral pathologies. It has
      been shown that PACAP protects neurons in rat models of both global and focal
      ischemia. In the present study, we investigated factors that may play a role in
      the neuroprotective effects of PACAP. PACAP strongly reduced the anisomycin
      induced apoptosis of PC12 cells, which was abolished in a PKA-deficient PC12 cell
      line (A126). This effect was also observed in vivo, in permanent occlusion of the
      middle cerebral artery, where the number of TUNEL-positive neurons was
      significantly reduced in the ischemic core of PACAP-treated animals. Our results
      show that PACAP has a minor antioxidant effect in a non-cellular in vitro system,
      and has considerable antioxidant effects in an in vitro red blood cell filtration
      model. PACAP had no effect on platelet aggregation induced by collagen, ADP or
      epinephrine. Our results demonstrate that the effects of PACAP on delayed
      neuronal death may play a significant role in the reduction of the infarct size
      in vivo, but the antioxidant effect could only be observed at concentrations
      higher than that used in the model of focal ischemia.

PMID- 15518895
TI  - Effects of pituitary adenylate cyclase activating polypeptide in a rat model of
      traumatic brain injury.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) is a widely
      distributed neuropeptide that has numerous different actions. Recent studies have
      shown that PACAP exerts neuroprotective effects not only in vitro but also in
      vivo, in animal models of global and focal cerebral ischemia, Parkinson's disease
      and axonal injuries. Traumatic brain injury has an increasing mortality and
      morbidity and it evokes diffuse axonal injury which further contributes to its
      damaging effects. The aim of the present study was to examine the possible
      neuroprotective effect of PACAP in a rat model of diffuse axonal injury induced
      by impact acceleration. Axonal damage was assessed by immunohistochemistry using
      an antiserum against beta-amyloid precursor protein, a marker of altered
      axoplasmic transport considered as key feature in axonal injury. In these
      experiments, we have established the dose response curves for PACAP
      administration in traumatic axonal injury, demonstrating that a single post
      injury intracerebroventricular injection of 100 microg PACAP significantly
      reduced the density of damaged, beta-amyloid precursor protein-immunoreactive
      axons in the corticospinal tract.

PMID- 15518894
TI  - Effect of pituitary adenylate cyclase-activating polypeptide 38 (PACAP38) on
      tissue oxygen content--treatment in central nervous system of mice.
AB  - It has been reported that pituitary adenylate cyclase-activating polypeptide
      (PACAP) plays an important role in preventing neuronal cell death and is also a
      potent vasodilator. Cerebral hypotension and hypoperfusion during cerebral
      ischemia and neurodegenerative diseases are well known as some of the negative
      factors which aggravate neuronal cell death. Nevertheless, the effect of PACAP on
      the cerebral circulation was not understood well. Therefore, in the present
      study, we determined the mean arterial blood pressure (MBP), regional cerebral
      blood flow (rCBF) and cerebral oxygen content (pO2) in mice, and estimated the
      therapeutically useful doses of PACAP. Under barbiturate anesthesia, polyethylene
      tubes were inserted into mice to monitor MBP and to administer PACAP (5 x 10(-13)
      5 x 10(-8) mol/kg) or vasoactive intestinal peptide (VIP; 5 x 10(-12) and 5 x 10(
      9) mol/kg). Then, MBP, rCBF and cerebral pO2 were simultaneously measured in the
      mice. PACAP (5 x 10(-10)-5 x 10(-9) mol/kg) injections transiently decreased MBP,
      and cerebral pO2. PACAP (5 x 10(-8) mol/kg) injections produced a long-lasting
      potent decline of MBP, rCBF and cerebral pO2. Therefore, PACAP should be applied
      at low doses which do not influence the MBP and cerebral circulation to determine
      the therapeutically useful doses of PACAP for neuroprotection.

PMID- 15518896
TI  - Effects of hypoxia on endothelial/pericytic co-culture model of the blood-brain
      barrier.
AB  - The blood-brain barrier (BBB) is composed of endothelial cells, pericytes and
      astrocytic foot processes. Most research for the in vitro BBB is performed
      endothelial cells with or without astrocytes. Hypoxia damage to the BBB induces
      vasogenic brain edema. We have generated a new model of the BBB with brain
      endothelial cells and pericytes and have examined the effects of hypoxia using
      this model. Brain microvascular endothelial cells and pericytes were isolated
      from three-week-old male Wister rats using enzyme and mechanical homogenization.
      Three models (A: only endothelial monolayer, B: endothelial monolayer with
      pericytes non-contact condition, and C: contact condition) were made by culturing
      these cells using Transwell co-culture system and were exposed to hypoxic
      condition. We evaluated barrier function with transendothelial electrical
      resistance (TEER) and permeability of Evans blue-albumin and sodium fluorescein.
      The tightest barrier was observed in the endothelial/pericytic contact model.
      Despite hypoxia-induced disruption of the barrier in endothelial monolayer and
      non-contact co-culture models, a minimum of dysfunction was seen in the contact
      co-culture model. Therefore, it is considered that pericytes effect on the
      endothelia by secreting factors or through a gap junction. In short, pericytes
      induce endothelial maturation and a tighter barrier function, which supports the
      function against the hypoxic injury. Intercellular communication might be
      important to keep the BBB functional and stabilize in hypoxia.

PMID- 15518897
TI  - Morphological and functional effects of PACAP in 6-hydroxydopamine-induced lesion
      of the substantia nigra in rats.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) has several different
      actions in the nervous system, including neuroprotective effects. In the present
      study, we investigated the effects of different doses of PACAP on the functional
      and morphological outcome in a rat model of Parkinson's disease. Rats were given
      unilateral injections of 6-hydroxydopamine (6-OHDA) into the substantia nigra.
      PACAP-treated animals received 1, 0.1 or 0.01 microg PACAP as a pretreatment.
      Control animals without PACAP treatment displayed severe hypokinesia at 1 and 10
      days post-lesion when compared to normal animals or those receiving saline only.
      PACAP treatment resulted in less severe acute hypokinesia, and complete recovery
      by 10 days. Asymmetrical signs were observed in all lesioned animals 1 day post
      lesion. PACAP-treated animals, however, showed better recovery as they ceased to
      display asymmetrical signs 10 days later and showed markedly less apomorphine
      induced rotations. Best behavioral outcome was observed in animals treated with
      0.1 microg PACAP. Tyrosine-hydroxylase (TH) immunohistochemistry revealed
      increased number of dopaminergic neurons in the substantia nigra pars compacta
      and in the ventral tegmental area in all PACAP-treated rats in contrast to the
      severe cell loss in control animals. These results indicate that PACAP may be a
      promising therapeutic agent in Parkinson's disease.

PMID- 15518898
TI  - Reduced hypothermic and hypnotic responses to ethanol in PACAP-deficient mice.
AB  - Using pituitary adenylate cyclase-activating polypeptide (PACAP)-deficient mice,
      we investigated whether PACAP is involved in the intoxicating effects of ethanol.
      The structure of PACAP is highly conserved during evolution, and in Drosophila,
      loss-of-function mutations in a PACAP-like neuropeptide gene, amnesiac, result in
      impairment of memory retention and increased sensitivity to ethanol. In mice,
      PACAP deficiency is associated with impaired memory performance and hippocampal
      long-term potentiation (LTP), however, sensitivity to ethanol has not been well
      investigated. Here, we addressed this issue in our recently developed PACAP
      deficient mice. Sleep time (duration of the loss of righting reflex) was markedly
      shortened in PACAP-deficient mice compared with wild-type, although latency to
      the loss of righting reflex was not different between the two groups. Ethanol
      induced hypothermia in wild-type control mice was significantly reduced in PACAP
      deficient mice. Blood ethanol levels were not different between the two groups,
      excluding the possibility of increased ethanol metabolism. Thus, in contrast to
      that in Drosophila, PACAP deficiency in mammals caused a reduced sensitivity to
      ethanol. However, in both cases, PACAP or amnesiac products are likely to play
      significant roles in modifying the intoxicating effects of ethanol.

PMID- 15518899
TI  - Effects of in ovo treatment with PACAP antagonist on general activity, motor and
      social behavior of chickens.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) has been shown to
      influence nervous system development. The aim of the present study was to
      investigate the effects of in ovo treatment with the PACAP antagonist PACAP6-38
      during embryonic life (E8 and E16) on motor activity and social behavior in
      chicken. Our results showed that a single injection of PACAP6-38 during the first
      half of embryonic life caused subtle transient changes in general behavior and
      motor control when compared to saline-treated controls. Increased activity and
      reduced anxiety were observed also in a novel environment at 2 days after
      hatching. However, most of these behavioral differences disappeared by 2 weeks.
      PACAP6-38-treatment during the first half of embryonic life resulted in markedly
      reduced social behavior, which was still present at 2 weeks of age. Treatment
      during the second half of embryonic life resulted in no behavioral differences
      between control and PACAP6-38-treated chicken. PACAP content in different brain
      areas was not different between control and PACAP6-38-treated chicken at 5 days
      or 3 weeks of age, but it decreased significantly with age in both groups. In
      summary, our results show that PACAP6-38 treatment at E8 caused transient changes
      in motor behavior, and long-lasting reduction in social behavior.

PMID- 15518900
TI  - Pituitary adenylate cyclase activating polypeptide and PAC1 receptor signaling
      increase Homer 1a expression in central and peripheral neurons.
AB  - Pituitary adenylate cyclase activating polypeptides (PACAP) and PAC1 receptor
      signaling have diverse roles in central and peripheral nervous system development
      and function. In recent microarray analyses for PACAP and PAC1 receptor
      modulation of neuronal transcripts, the mRNA of Homer 1a (H1a), which encodes the
      noncrosslinking and immediate early gene product isoform of Homer, was identified
      to be strongly upregulated in superior cervical ganglion (SCG) sympathetic
      neurons. Given the prominent roles of Homer in synaptogenesis, synaptic protein
      complex assembly and receptor/channel signaling, we have examined the ability for
      PACAP to induce H1a expression in sympathetic, cortical and hippocampal neurons
      to evaluate more comprehensively the roles of PACAP in synaptic function. In both
      central and peripheral neuronal cultures, PACAP peptides increased transiently
      H1a transcript levels approximately 3.5- to 6-fold. From real-time quantitative
      PCR measurements, the temporal patterns of PACAP-mediated H1a mRNA induction
      among the different neuronal cultures appeared similar although the onset of
      sympathetic H1a transcript expression appeared protracted. The increase in H1a
      transcripts was accompanied by increases in H1a protein levels. Comparative
      studies with VIP and PACAP(6-38) antagonist demonstrated that the PACAP effects
      reflected PAC1 receptor activation and signaling. The PAC1 receptor isoforms
      expressed in central and peripheral neurons can engage diverse intracellular
      second messenger systems, and studies using selective signaling pathway
      inhibitors demonstrated that the cyclic AMP/PKA and MEK/ERK cascades are
      principal mediators of the PACAP-mediated H1a induction response. In modulating
      H1a transcript and protein expression, these studies may implicate broad roles
      for PACAP and PAC1 receptor signaling in synaptic development and plasticity.

PMID- 15518901
TI  - Diverse effects of intrathecal pituitary adenylate cyclase-activating polypeptide
      on nociceptive transmission in mice spinal cord.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) immunoreactive neural
      elements have been detected in the mouse spinal cord. The discrepancy of PACAP
      actions in the role of sensory transmission has been proposed to have
      potentiation and inhibition on nociceptive responses after intrathecal
      application of PACAP. The aim of the present study was to assess nociceptive
      transmission of PACAP in the mouse spinal cord by comparison with that of
      substance P (SP). The intrathecal injection of PACAP induced licking or
      scratching behavior similar to that of SP. These PACAP-induced aversive behaviors
      showed different manner from SP-induced responses in point of time course. SP
      induced aversive responses quickly increased and suddenly disappeared almost
      within 1 min. Meanwhile, following a long latency after the injection, PACAP
      induced aversive responses gradually appeared, and then persisted more than 60
      min. In the early phase, PACAP produced an increase of tail flick latency.
      Pretreatment with 6-hydroxydopamine (6-OHDA) which destroys noradrenaline neuron
      of descending pain inhibitory systems in the spinal cord markedly abridged the
      latency and augmented the duration of PACAP-induced aversive responses. In this
      way, PACAP exhibits diverse effects on nociception, such as an analgesic role in
      early phase of the injection and subsequently lasting algesia. These results
      suggest that PACAP as a neurotransmitter or neuromodulator might have crucial
      role in nociceptive transmission system.

PMID- 15518902
TI  - Pituitary adenylate cyclase-activating polypeptide enhances the hyperpolarization
      activated nonselective cationic conductance, Ih, in dissociated guinea pig
      intracardiac neurons.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) peptides, which are co
      localized with acetylcholine in preganglionic parasympathetic fibers innervating
      guinea pig intracardiac ganglia, depolarize and increase excitability of
      intracardiac neurons. Perforated patch whole cell recordings were used to test
      whether PACAP27-enhanced activation of Ih contributed to the increase in
      excitability. In current clamp, 100 nM PACAP27 increased rectification during 500
      ms hyperpolarizations and increased the number of anodal break action potentials
      (APs). PACAP27 also increased the number of APs produced by 500-ms depolarizing
      currents. In voltage clamp, the effects of 100 nM PACAP27 were determined during
      hyperpolarizing steps from -50 mV to voltages between -60 and -120 mV. PACAP27
      increased the amplitude and rate of activation of Ih. PACAP27 shifted the voltage
      dependence of activation of Ih by 6.6 mV. The effect of PACAP27 was eliminated by
      pretreatment with the Ih inhibitor ZD7288 (100 microM). The adenylyl cyclase
      activator forskolin (10 microM) produced a similar shift in the voltage
      dependence of Ih activation. We conclude that PACAP27 enhances Ih by shifting the
      voltage dependence of activation and propose that this effect is mediated
      primarily by PAC1 receptor activation of adenylyl cyclase and generation of cAMP.
      Furthermore, we propose that the peptide-enhanced Ih contributes to the PACAP27
      induced increase in membrane excitability.

PMID- 15518903
TI  - PACAP facilitate the nerve regeneration factors in the facial nerve injury.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) has been reported as a
      strong neurotrophic factor in the various sites of nervous system. The facial
      nerve injury is one of the common problems in patients at the Otolaryngology
      since the nerve damage could occur easily due to the anatomical characteristics.
      Once it happens, the regeneration is little observed and functional recovery is
      poor. Thus, we investigated that PACAP might have some influence for regeneration
      after the facial nerve transaction in the guinea pig. PACAP treatment accelerated
      time for the appearance of compound muscle action potentials (CMAP) after the
      nerve transaction (first appeared at 1 versus 2 weeks in control) and shortened
      the latency at 4 weeks. The number of myelinated fibers increased at 4 weeks.
      Histochemical demonstration of GAP-43, a growth cone protein, was observed at the
      injury area at 2-4 days. PACAP increased the level of glial cell line-derived
      neurotrophic factor (GDNF), a neurotrophin, in facial target muscles at 1 day-4
      weeks. These data indicated that PACAP promotes the regeneration factors and
      increases the possibility of functional recovery following the facial nerve
      injury.

PMID- 15518904
TI  - Effect of PACAP on LH release studied by cell immunoblot assay depends on the
      gender, on the time of day and in female rats on the day of the estrous cycle.
AB  - We have previously demonstrated that pituitary adenylate cyclase activating
      polypeptide (PACAP) can be released from cultured rat anterior pituitary cells
      and when added to the medium in physiological concentration it releases LH from
      individual gonadotropes. In the present work, we studied whether the release of
      PACAP and the responsiveness of LH cells to PACAP depend on the gender, on the
      time of day when the animals were sacrificed, and in females on the stage of the
      estrous cycle. Anterior pituitary cells were cultured on nitrocellulose membrane.
      We found that the number of PACAP releasing cells was higher in proestrous than
      in diestrous female or in male rats and their number was always higher in the
      evening than at the other times. The effect of PACAP on LH cells was stimulatory
      in the morning of proestrus and diestrus. In proestrous rats, PACAP did not
      influence LH release in the afternoon or the evening, but in diestrous rats it
      decreased it in the afternoon and the evening. In males, there was a decrease of
      LH due to PACAP treatment at 10 and 20 h; however, PACAP did not influence LH at
      16 h. It was concluded that in vivo PACAP might be involved in the circadian and
      episodic release of LH at pituitary level.

PMID- 15518905
TI  - Cytosolic Ca2+ responses to sub-picomolar and nanomolar PACAP in pancreatic beta
      cells are mediated by VPAC2 and PAC1 receptors.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) potentiates glucose
      induced insulin release and increases cytosolic Ca2+ concentration ([Ca2+]i) in
      islet beta-cells in a concentration-dependent manner with two peaks at 10(-13)
      and 10(-9) M. PAC1 receptor (PAC1-R) and VPAC2 receptor (VPAC2-R) are expressed
      in pancreatic beta-cells and thought to be involved in insulin release. We aimed
      to determine the receptor types involved in the [Ca2+]i responses to 10(-13) and
      10(-9) M PACAP. We measured [Ca2+]i in beta-cells and examined comparative
      effects of PAC1-R-selective agonist maxadilan, its antagonist M65, VPAC2-R
      selective agonist Ro25-1553, and native ligands of PACAP and VIP. In the presence
      of 8.3 mM glucose, maxadilan, Ro25-1553, PACAP, and VIP at 10(-13) and 10(-9) M
      all increased [Ca2+]i. PACAP and maxadilan elicited greater effects at 10(-9) M
      than at 10(-13) M both in the incidence and amplitude of [Ca2+]i responses. For
      VIP and Ro25-1553, in contrast, the effects at 10(-9) and 10(-13) M were
      comparable. Furthermore, the amplitude of [Ca2+]i responses to 10(-9) M PACAP,
      but not 10(-13) M PACAP, was suppressed by M65. The results suggest that VPAC2-R
      and PAC1-R contribute equally to [Ca2+]i responses to sub-picomolar
      concentrations of PACAP, while PAC1-R has greater contribution to [Ca2+]i
      responses to nanomolar concentrations of this peptide.

PMID- 15518906
TI  - Overexpression of PACAP in the pancreas failed to rescue early postnatal
      mortality in PACAP-null mice.
AB  - PACAP exerts multiple activities as a hormone and neurotransmitter, and has been
      proposed to play vital roles in a variety of neuronal functions. PACAP is also
      involved in insulin secretion from pancreatic beta-cells. Recently, we and other
      groups demonstrated that PACAP-deficient mice (PACAP(-/-)) are viable, but suffer
      from increased postnatal mortality. To ascertain whether this high mortality is
      rescued by overexpression of PACAP in peripheral tissue (such as pancreas), we
      performed a genetic cross between PACAP(-/-) and our recently developed
      transgenic mice overexpressing PACAP in pancreatic beta-cells; and then examined
      the survival rate of their F2 progeny. PACAP(-/-) mice were segregated into two
      groups based on mortality as well as body weight gain: PACAP(-/-) that survived
      >20 days of age with normal weight gain and PACAP(-/-) that died before 20 days
      with a marked weight loss. Kaplan-Meier survival analysis demonstrated that
      PACAP(-/-) mice and those carrying the PACAP transgene have similarly lower
      survival probability compared with their heterozygous littermates that served as
      positive controls. Further study using additional tissue-specific transgenic or
      knockout mouse models will be required to determine the causative defects
      underlying the high mortality of PACAP(-/-) mice.

PMID- 15518907
TI  - Long-lasting smooth-muscle relaxation by a novel PACAP analogue in human bronchi.
AB  - We compared the relaxant effect of original pituitary adenylate cyclase
      activating peptide (PACAP)1-27 with that of a newly developed, synthetic PACAP1
      27 analogue, [Arg15,20,21 Leu17]-PACAP-Gly-Lys-Arg-NH2, in human bronchi in vitro
      (n=4-5 in each group). Using precontraction by carbachol (0.1 microM), cumulative
      administration of PACAP1-27 and salbutamol caused concentration-dependent smooth
      muscle relaxation with similar potencies and maximum relaxant effects. Non
      cumulative administration of the PACAP1-27 analogue and the original PACAP1-27
      caused concentration-dependent relaxation with a similar maximum relaxant effect
      and potency as well. However, the onset and offset of action was markedly slower
      for the PACAP1-27 analogue than for the original PACAP1-27 (>90% versus <10% of
      peak relaxation remaining 5 h after administration). Peptidase inhibition by
      captopril (10 microM) and phosphoramidon (1 microM) significantly increased the
      maximum relaxant effect and duration of action of PACAP1-27 but not of the PACAP1
      27 analogue, during the 3 h of observation in the human bronchi. We conclude that
      [Arg15,20,21 Leu17]-PACAP-Gly-Lys-Arg-NH2 produces significant concentration
      dependent and sustained bronchial smooth muscle relaxation in vitro. The
      sustained relaxant effect is due, at least in part, to the synthetic PACAP1-27
      analogue being less susceptible to cleavage by peptidases than the original
      peptide PACAP1-27.

PMID- 15518908
TI  - Expression of PAC1 receptor in rat thymus after irradiation.
AB  - In the present work, PAC1-R (G-protein-coupled receptor specific for PACAP) was
      detected on cells in the normal thymus. Immunohistochemically PAC1-R was
      expressed strongly in stromal cells of the thymic medulla. Positive cells were
      also observed in the thymus of fetal and old adult rats. After 8 Gy irradiation
      to 9-week-old rats, PAC1-R expressions in the thymus decreased and almost
      recovered by day 21. The expression of PAC1-R mRNA was weak in the thymus and
      decreased further after irradiation. The expression almost recovered by day 28.
      Hip and hip/hop variants, which were not expressed in the normal thymus, were
      expressed in the thymus on days 3, 5 and 21 after irradiation. The expressions of
      IL-6 and IL-10 tended to increase initially after irradiation then decreased.
      Histologically, the thymic structures were destroyed on day 3 after irradiation
      and the thymus almost recovered by day 21. Thus PACAP is thought to be one of the
      important factors for cross-talk between cells involved in thymic regeneration.

PMID- 15518909
TI  - Isolation and characterization of four VIP-related peptides from red-bellied
      newt, Cynops pyrrhogaster.
AB  - Four novel bioactive peptides were isolated from the red-bellied newt, Cynops
      pyrrhogaster, using a bioassay system monitoring the rectum contraction of the
      Japanese quail, Coturnix japonica. As these peptides are structurally related to
      vasoactive intestinal polypeptide (VIP), we termed these peptides newt VIP
      related peptides 1, 2, 3, and 4 (NVRP-1, -2, -3, and -4). The primary sequences
      of these peptides were determined to be HSDAVFTDNYSRLLGKTALKNYLDGALKKE (NVRP-1),
      HSDAVFTDNYSRLLAKTALKNYLDGALKKE (NVRP-2), HSDAVFT-DNYSRLLGKIALKNYLDEALKKE (NVRP
      3), and HSDAVFTDNYSRLLGKT-ALKNYLDSALKKE (NVRP-4). The N-terminal regions of these
      NVRPs possessed homology at the amino-acid level to various VIP, while the NVRP C
      termini differed from VIPs significantly. All of the VIP consist of 28 amino-acid
      residues with amidated forms at the C-termini, whereas NVRPs possess 30 amino
      acid residues and have free forms at the C-termini. NVRPs exert relaxant
      activities on isolated quail rectums in a dose-dependent manner, with threshold
      concentrations between 1 x 10(-8) and 3 x 10(-8) M. NVRPs also exhibited potent
      relaxant activities acting on the newt duodenum at 3 x 10(-8) M. As yet, this is
      the first isolation of biologically active VIP-related peptides from urodele.

PMID- 15518910
TI  - Presence of a N-terminal signal peptide in class II G protein-coupled receptors:
      crucial role for expression of the human VPAC1 receptor.
AB  - The hVPAC1 receptor for vasoactive intestinal peptide (VIP) and pituitary
      adenylyl cyclase activating peptide (PACAP) has an N-terminal signal peptide like
      all other class II G protein-coupled receptors (GPCRs). We determined the role of
      the signal peptide in expression of human VPAC1 receptor in transfected CHO
      cells. Three constructs were transfected: Flag30-hVPAC1, a receptor containing an
      inserted FLAG sequence between Ala30 and Ala31 and fused in the C-terminal
      position to GFP; Flag30-[delta1-30]-hVPAC1, the same construct as Flag30-hVPAC1
      but lacking the 1-30 putative signal peptide (SP) sequence; Flag0-hVPAC1, a
      receptor containing an N-terminal FLAG sequence and fused in the C-terminal
      position to GFP. For each construct, we determined 125I-VIP binding, VIP-induced
      cAMP production, GFP fluorescence and indirect immunofluorescence on
      nonpermeabilized cells incubated with mouse monoclonal anti-Flag antibodies. The
      data were consistent with a crucial role of the signal peptide for expression of
      functional VPAC1 receptors at the cell surface and suggested that the signal
      peptide is cleaved during the translocation of the receptor to the plasma
      membrane, probably in the endoplasmic reticulum.

PMID- 15518911
TI  - The development of VIP-ellipticine conjugates.
AB  - The mechanism by which vasoactive intestinal peptide (VIP)-ellipticine (E)
      conjugates are cytotoxic for human lung cancer cells was investigated. VIP-alanyl
      leucyl-alanyl-leucyl-alanine (ALALA)-E and VIP-leucyl-alanyl-leucyl-alanine
      (LALA)-E inhibited (125)I-VIP binding to NCI-H1299 cells with an IC50 values of
      0.5 and 0.1 microM, respectively. VIP-ALALA-E and VIP-LALA-E caused elevation of
      cAMP in NCI-H1299 cells with ED50 values of 0.7 and 0.1 microM. Radiolabeled VIP
      LALA-E was internalized at 37 degrees C and delivered the cytotoxic E into NCI
      H1299 cells. VIP-LALA-E inhibited the growth of NCI-H1299 cells in vitro. Three
      days after the addition of VIP-LALA-E to NCI-H1299 cells, cell viability
      decreased based on trypan blue exclusion and reduced 3H-thymidine uptake. These
      results suggest that VIP-E conjugates are internalized in lung cancer cells as a
      result of VPAC1 receptor-mediated endocytosis.

PMID- 15518912
TI  - Long-acting analogue of vasoactive intestinal peptide, [R15, 20, 21, L17]-VIP-GRR
      (IK312532), protects rat alveolar L2 cells from the cytotoxicity of cigarette
      smoke.
AB  - Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating
      polypeptide (PACAP) act as neurotransmitters in numerous biological responses. We
      previously reported that the replacement of Lys by Arg, and Met by Leu in VIP
      (IK312532; [Arg15, 20, 21, Leu17]-VIP) resulted in a significant improvement in
      metabolic stability and biological activity. In the present study, we
      investigated the effect of VIP and its related peptides including long-acting VIP
      derivative (IK312532) and PACAP27 on the cytotoxicity of cigarette smoke extract
      (CSE), a causative factor of chronic obstructive pulmonary disease (COPD), in rat
      alveolar L2 cells. RT-PCR displayed the dominant expression of mRNA for the VIP
      specific VPAC2 receptor in L2 cells, and VIP and the related peptides showed the
      specific binding activity and potent stimulation of adenylate cyclase. CSE at a
      concentration of 0.1% or higher induced significant apoptotic death of L2 cells.
      Interestingly, the addition of neuropeptides at a concentration of 10(-11) M or
      higher in L2 cells with CSE (0.25%) resulted in significant attenuation of cell
      death with the deactivation of CSE-evoked caspase-3 activity. IK312532 was much
      stable against the enzymatic digestion compared to VIP, and the protective effect
      of IK312532 was 1.6-fold higher than that of VIP. Taken together with our
      previous report showing that IK312532 has long-acting relaxant activity in the
      lung, IK312532 may be a potential candidate for drug treatment of asthma and
      COPD.

PMID- 15518913
TI  - Pharmacological effects and lung-binding characteristics of a novel VIP analogue,
      [R15, 20, 21, L17]-VIP-GRR (IK312532).
AB  - A novel VIP derivative, [R15, 20, 21, L17]-VIP-GRR (IK312532), relaxed potently
      the carbachol-induced contraction of guinea-pig isolated trachea with longer
      duration than that induced by VIP. IK312532 competed with [125I]VIP for the
      binding sites in the rat lung in a concentration-dependent manner. There was
      considerable decrease in specific [125I]VIP binding in each lobe of right and
      left lung 0.5 h after the intratracheal administration of IK312532 (50
      microg/rat) as dry powder inhaler (DPI). Rosenthal analysis revealed that the
      administration of IK312532 (50 and 100 microg/rat)-DPI brought about a
      significant decrease of maximal number of binding sites (Bmax) for specific
      [125I]VIP binding in anterior and posterior lobes of rat right lung, suggesting a
      significant occupancy of lung VIP receptors. This effect by IK312532 in the
      posterior lobe of the right lung was dose-dependent and lasted until at least 2 h
      after the intratracheal administration. Furthermore, the antigen-evoked
      infiltration of granulocytes in the rat bronchiolar mucosa was markedly
      suppressed by the intratracheal administration of IK312532 (50 microg/rat)-DPI.
      In conclusion, the present study has shown that IK312532 exhibits long-lasting
      relaxation of tracheal smooth muscles and that the intratracheal administration
      of this peptide exerts a significant occupancy of lung VIP receptors as well as a
      suppression of the antigen-evoked infiltration of granulocytes in the bronchiolar
      mucosa. Thus, the formulation of IK312532 as DPI may be a pharmacologically
      useful drug delivery system for the therapy of pulmonary diseases such as asthma.

PMID- 15518914
TI  - Secretin and autism: a basic morphological study about the distribution of
      secretin in the nervous system.
AB  - For the first time, the relationship between secretin and autism has been
      demonstrated by one of us. Intravenous administration of secretin in autistic
      children caused a fivefold higher pancreaticobiliary fluid secretion than in
      healthy ones and, at least in some of the patients, better mental functions were
      reported after the secretin test. Because the precise localization of secretin in
      the brain is still not completely known, the abovementioned observation led us to
      map secretin immunoreactivity in the nervous system of several mammalian species.
      In the present work, the distribution of secretin immunoreactivity in cat and
      human nervous systems was compared with that of rats using an immunohistochemical
      approach. Secretin immunoreactivity was observed in the following brain
      structures of both humans and in colchicine-treated rats: (1) Purkinje cells in
      the cerebellar cortex; (2) central cerebellar nuclei; (3) pyramidal cells in the
      motor cortex; and (4) primary sensory neurons. Additionally, secretin
      immnoreactive cells were observed in the human hippocampus and amygdala and in
      third-order sensory neurons of the rat auditory system. In cats, secretin was
      only observed in the spinal ganglia. Our findings support the view that secretin
      is not only a gastrointestinal peptide but that it is also a neuropeptide. Its
      presence or the lack of its presence may have a role in the development of
      behavioral disorders.

PMID- 15518915
TI  - Functional characterization and purification of the secretin receptor expressed
      in baculovirus-infected insect cells.
AB  - Structural insights into Class II G protein-coupled receptors have been limited
      by the absence of a plentiful and highly enrichable source such as rhodopsin in
      the Class I family. With structural differences predicted to exist between these
      families, and with the key importance of an intact, disulfide-bonded amino
      terminal domain for the Class II receptors, an overproduction and purification
      scheme is critically important. In this work, we have established and
      characterized a baculoviral expression and purification system for the secretin
      receptor. Hemagglutinin epitope-tagged wild-type rat secretin receptor construct
      was expressed using the recombinant baculovirus/Sf9 insect cell-based system,
      achieving a level of expression substantially higher than that previously
      achieved in Chinese hamster ovary (CHO-SecR) cells. Receptor expressed in Sf9
      cells had similar affinity for secretin (Ki=1.4+/-0.2 nM) and similar potency to
      stimulate intracellular cAMP in response to this hormone (EC50=194+/-45 pM) as
      did wild-type receptor expressed in CHO cells. Receptors from Sf9 cells were also
      affinity labeled saturably and specifically by a photolabile secretin analogue.
      The receptors were purified to homogeneity by solubilization with sodium
      deoxycholate, selective ammonium sulfate precipitation, gel filtration and
      immunoaffinity purification. This expression system should facilitate the
      structural characterization of this receptor and its important amino-terminal
      domain.

PMID- 15518916
TI  - Motor hyperactivity caused by a deficit in dopaminergic neurons and the effects
      of endocrine disruptors: a study inspired by the physiological roles of PACAP in
      the brain.
AB  - Recent studies have revealed that the pituitary adenylate cyclase-activating
      polypeptide (PACAP) might act as a psychostimulant. Here we investigated the
      mechanisms underlying motor hyperactivity in patients with pervasive
      developmental disorders, such as autism, and attention-deficit hyperactivity
      disorder (ADHD). We studied the effects of intracisternal administration of 6
      hydroxydopamine (6-OHDA) or endocrine disruptors (EDs) on spontaneous motor
      activity (SMA) and multiple gene expression in neonatal rats. Treatment with 6
      OHDA caused significant hyperactivity during the dark phase in rats aged 4-5
      weeks. Motor hyperactivities also were observed after treatment with endocrine
      disruptors, such as bisphenol A, nonylphenol, diethylhexyl phthalate and dibutyl
      phthalate, during both dark and light phases. Gene-expression profiles produced
      using cDNA macroarrays of 8-week-old rats with 6-OHDA lesions revealed the
      altered expression of several classes of gene, including the N-methyl-D-aspartate
      (NMDA) receptor 1, glutamate/aspartate transporter, gamma-aminobutyric-acid
      transporter, dopamine transporter 1, D4 receptor, and peptidergic elements such
      as the galanin receptor, arginine vasopressin receptor, neuropeptide Y and
      tachykinin 2. The changes in gene expression caused by treatment with endocrine
      disruptors differed from those induced by 6-OHDA. These results suggest that the
      mechanisms underlying the induction of motor hyperactivity and/or compensatory
      changes in young adult rats might differ between 6-OHDA and endocrine disruptors.

PMID- 15518918
TI  - Coming out of the dark: the evolving role of fluorescence imaging in drug
      delivery research.

PMID- 15518919
TI  - Fluorescence techniques for drug delivery research: theory and practice.
AB  - Advances in drug delivery require an understanding of drug design, drug stability
      and metabolism together with the complexities imposed by the biological system
      such as cell/tissue penetration, drug-target interaction, and the pharmacodynamic
      consequences. Fluorescence microscopy provides a comprehensive tool for
      investigating many of these aspects of drug delivery in single cells and whole
      tissue. This review presents the fundamental concepts of fluorescence-based
      methodologies. The core principles which underlie the fluorescence process and
      the interpretation of these events drives instrument design and the components
      required to illuminate and detect fluorescent probes. Many drugs are inherently
      auto-fluorescent and therefore can be tracked using microscopy techniques, while
      other more indirect approaches assay the consequences of drug perturbation. This
      review addresses the two principle aims in fluorescence microscopy; to generate
      and enhance fluorescence-derived contrast that may reveal a central process of
      drug delivery.

PMID- 15518920
TI  - Intracellular trafficking pathways and drug delivery: fluorescence imaging of
      living and fixed cells.
AB  - Cellular processes depend on the fidelity of intracellular membrane traffic.
      Lipids, proteins, receptor ligands and solute molecules are trafficked to
      distinct compartments within the cell through both the biosynthetic and endocytic
      pathways. An appreciation of these pathways is vital for a complete understanding
      of intracellular drug delivery. Recent advances in fluorescence imaging have
      facilitated the analysis of these pathways in great detail. It is now possible to
      gain insight into the real-time dynamics of cellular components and
      macromolecular pharmacological agents as they are delivered into and traffic
      within single cells. Here, we discuss the analysis of intracellular drug delivery
      from the perspective of fluorescence imaging of both living and fixed cells. This
      review aims to cover trafficking pathways, markers for subcellular compartments,
      fluorescent labels for intracellular structures and pharmacological agents and
      relevant recent developments in imaging technology. In particular, we shall focus
      on the application of live cell imaging to the study of endocytic drug delivery.

PMID- 15518921
TI  - Real-time multiple-particle tracking: applications to drug and gene delivery.
AB  - Complex biological environments, such as the cell cytoplasm or the mucus lining
      the airways of the lungs, can pose significant barriers to efficient therapeutic
      drug and gene delivery. Biological barriers are particularly important in
      controlled drug delivery applications that utilize a large carrier particle, such
      as a liposome or a polymer micro- or nanosphere. The dynamic transport of
      particulate drug and gene delivery vehicles through these barriers is poorly
      understood, having been primarily studied with static methods in the past.
      Recently, the transport of synthetic drug and gene carriers has been investigated
      quantitatively with real-time particle tracking technology, providing new insight
      into particle behavior in complex biological environments that is guiding
      rational improvements in particle design. This review briefly highlights basic
      principles of particle tracking and its application to elucidate important
      phenomena that limit effective particulate drug and gene delivery.

PMID- 15518922
TI  - Imaging living central neurones using viral gene transfer.
AB  - Studies of central neurones and other cellular components of the brain, such as
      glial and vascular cells, can be greatly advanced by the use of the modern
      optical techniques such as confocal live cell imaging. Fluorescent proteins have
      allowed imaging of particular cell types or intracellular elements to be
      visualised and distinguished from irrelevant background structures. To introduce
      the genetic information encoding for fluorescent proteins into relevant cellular
      targets, molecular tools are required. Viral vectors are one of the best ways of
      gene delivery into differentiated postnatal brain neurones and glia. Current
      progress in this field allows targeting of various cell types and therefore makes
      it possible to express a variety of fluorescent constructs in selected
      subpopulations of neurones, for example. In this review, we will discuss and
      compare the properties of the most popular viral gene delivery systems and the
      advantages of different brain cell preparations to illustrate how they can be
      used for high-resolution live cell confocal imaging in order to study new aspects
      of central nervous system (CNS) structure and function.

PMID- 15518923
TI  - Fluorescence microscopy to follow the targeting of liposomes and micelles to
      cells and their intracellular fate.
AB  - Fluorescence microscopy may provide important information regarding interactions
      between nanoparticulate drugs carriers, such as liposomes and micelles, with
      target cells as well as their intracellular fate. Current paper describes various
      applications of fluorescence microscopy to investigate specific targeting of
      antibody-modified drug carriers to cancer cells. The enhanced antibody-mediated
      targeting of drug-loaded immunomicelles confirmed by fluorescence microscopy
      resulted in enhanced cancer cell killing compared to free drug or drug-loaded
      nontargeted micelles. Fluorescence microscopy was also used to prove the
      endosomal escape of properly assembled polymeric micelles (based on polyethylene
      glycol-phosphatidylethanolamine conjugate, PEG-PE) containing various additives
      destabilizing the endosomal membrane. When loaded with the anticancer drug
      (paclitaxel or vitamin K3), such micelles demonstrate increased cytotoxicity.
      Fluorescence microscopy was also applied to investigate the capture of cell
      penetrating TAT peptide-modified liposomes by various cells and stability and
      intracellular trafficking of captured TAT-liposomes inside cells. It was also
      used to confirm the successful transfection of cells with TAT-liposomes bearing
      the plasmid encoding for the Green Fluorescent Protein (GFP).

PMID- 15518924
TI  - Applications of imaging techniques to studies of epithelial tight junctions.
AB  - The intercellular junctional complex, which consists of the tight junction (TJ),
      adherens junction, and desmosomes, mediates cell-cell adhesion in epithelia and
      endothelia. The TJ forms the apical-most portion of this complex in epithelia,
      serving as a fence to lateral diffusion of apical and basolateral membrane
      components and as a semi-permeable barrier or gate to the flow of ions and
      solutes through the paracellular pathway. The TJ consists of a series of integral
      membrane and cytoplasmic plaque proteins with complex interactions. Included
      among the TJ proteins are the claudins, which play a major role in mediating the
      charge and solute selectivity of the junction. Yet, the profile of claudin and
      associated protein expression differs among epithelia and the function and
      regulation of many of the TJ proteins remain unknown. This review discusses the
      application of techniques to discern the function, localization, and regulation
      of epithelial TJs based on examples from published studies.

PMID- 15518925
TI  - Use of fluorescence imaging to investigate the structure and function of
      intestinal M cells.
AB  - Fluorescence imaging technology can be applied to many aspects of cell biology
      ranging from the analysis of specific markers in cells and tissues to the
      biological actions and distribution of fluorescent proteins or particles in
      living cells. In this review, we examine the role of fluorescence imaging, in
      conjunction with other microscopical techniques, to study sites of uptake of
      material across the gastrointestinal epithelium. We will focus primarily on
      intestinal M cells, specialised antigen-sampling cells in the epithelium of the
      gut-associated lymphoid tissue (GALT), including Peyer's patches. In addition to
      their importance as sites for uptake of inert material, and hence their potential
      as a route of delivery of vaccines, etc., M cells are also a major site of
      infection by a range of microbial pathogens. The application of new fluorescence
      imaging technologies has expanded our knowledge on the structure, development and
      function of these fascinating cells.

PMID- 15518926
TI  - Intravital imaging of tumour vascular networks using multi-photon fluorescence
      microscopy.
AB  - The blood supply of solid tumours affects the outcome of treatment via its
      influence on the microenvironment of tumour cells and drug delivery. In addition,
      tumour blood vessels are an important target for cancer therapy. Intravital
      microscopy of tumours growing in 'window chambers' in animal models provides a
      means of directly investigating tumour angiogenesis and vascular response to
      treatment, in terms of both the morphology of blood vessel networks and the
      function of individual vessels. These techniques allow repeated measurements of
      the same tumour. Recently, multi-photon fluorescence microscopy techniques have
      been applied to these model systems to obtain 3D images of the tumour
      vasculature, whilst simultaneously avoiding some of the problems associated with
      the use of conventional fluorescence microscopy in living tissues. Here, we
      review the current status of this work and provide some examples of its use for
      studying the dynamics of tumour angiogenesis and vascular function.

PMID- 15518927
TI  - Advanced microscopy solutions for monitoring the kinetics and dynamics of drug
      DNA targeting in living cells.
AB  - Many anticancer drugs require interaction with DNA or chromatin components of
      tumor cells to achieve therapeutic activity. Quantification and exploration of
      drug targeting dynamics can be highly informative in the rational development of
      new therapies and in the drug discovery pipeline. The problems faced include the
      potential infrequency and transient nature of critical events, the influence of
      micropharmacokinetics on the drug-target equilibria, the dependence on preserving
      cell function to demonstrate dynamic processes in situ, the need to map events in
      functional cells and the confounding effects of cell-to-cell heterogeneity. We
      demonstrate technological solutions in which we have integrated two-photon laser
      scanning microscopy (TPLSM) to track drug delivery in subcellular compartments,
      with the mapping of sites of critical molecular interactions. We address key
      design concepts for the development of modular tools used to uncover the
      complexity of drug targeting in single cells. First, we describe the combination
      of two-photon excitation with fluorescence lifetime imaging microscopy (FLIM) to
      map the nuclear docking of the anticancer drug topotecan (TPT) at a subset of DNA
      sites in nuclear structures of live breast tumor cells. Secondly, we demonstrate
      how we incorporate the smart design of a two-photon 'dark' DNA binding probe,
      such as DRAQ5, as a well-defined quenching probe to uncover sites of drug
      interaction. Finally, we discuss the future perspectives on introducing these
      modular kinetic assays in the high-content screening arena and the interlinking
      of the consequences of drug-target interactions with cellular stress responses.

PMID- 15518928
TI  - Fluorescence correlation spectroscopy of molecular motions and kinetics.
AB  - The foundations for fluorescence correlation spectroscopy (FCS) were already laid
      in the early 1970s, but this technique did not become widely used until single
      molecule detection was established almost 20 years later with the use of
      diffraction-limited confocal volume element. The analysis of molecular noise from
      the GHz- to the Hz-region facilitates measurements over a large dynamic range
      covering photophysics, conformational transitions and interactions as well as
      transport properties of fluorescent biomolecules. From the Poissonian nature of
      the noise spectrum the absolute number of molecules is obtainable. Originally
      used for the analysis of molecular interactions in solutions, the strength of FCS
      lies also in its applicability to molecular processes at either the surface or
      interior of single cells. Examples for the analysis of surface kinetics including
      on and off rates of ligand-receptor interactions will be given. The possibility
      of obtaining this type of information by FCS will be of particular interest for
      cell-based drug screening.

PMID- 15518929
TI  - Studying biophysical barriers to DNA delivery by advanced light microscopy.
AB  - Advanced light microscopy (ALM) has been intensively employed by biophysicists to
      reveal cellular mechanisms. As described in this review, ALM clearly has
      potential to enhance our understanding of the mechanisms that affect
      macromolecular therapeutics or nanoscopic drug vectors in biological
      environments. However, while in recent years confocal microscopy and related
      techniques became rather routinely used in drug delivery it remains challenging
      to extract reliable information on the biophysical behaviour of drug delivery
      systems from ALM measurements. This review discusses studies in which confocal
      imaging, fluorescence recovery after photobleaching (FRAP), fluorescence
      correlation spectroscopy (FCS) and fluorescence energy transfer were employed to
      reveal biophysical properties of DNA and DNA containing nanoparticles in extra-
      and intracellular media.

PMID- 15518930
TI  - Neurocognitive mechanisms of cognitive control: the role of prefrontal cortex in
      action selection, response inhibition, performance monitoring, and reward-based
      learning.
AB  - Convergent evidence highlights the differential contributions of various regions
      of the prefrontal cortex in the service of cognitive control, but little is
      understood about how the brain determines and communicates the need to recruit
      cognitive control, and how such signals instigate the implementation of
      appropriate performance adjustments. Here we review recent progress from
      cognitive neuroscience in examining some of the main constituent processes of
      cognitive control as involved in dynamic decision making: goal-directed action
      selection, response activation and inhibition, performance monitoring, and reward
      based learning. Medial frontal cortex is found to be involved in performance
      monitoring: evaluating outcome vis-a-vis expectancy, and detecting performance
      errors or conflicting response tendencies. Lateral and orbitofrontal divisions of
      prefrontal cortex are involved in subsequently implementing appropriate
      adjustments.

PMID- 15518931
TI  - Prefrontal and hippocampal contributions to visual associative recognition:
      interactions between cognitive control and episodic retrieval.
AB  - The ability to recover episodic associations is thought to depend on medial
      temporal lobe mnemonic mechanisms and frontal lobe cognitive control processes.
      The present study examined the neural circuitry underlying non-verbal associative
      retrieval, and considered the consequences of successful retrieval on cognitive
      control demands. Event-related fMRI data were acquired while subjects retrieved
      strongly or weakly associated pairs of novel visual patterns in a two-alternative
      forced choice associative recognition paradigm. Behaviorally, successful
      retrieval of strongly associated relative to weakly associated pairs was more
      likely to be accompanied by conscious recollection of the pair's prior co
      occurrence. At the neural level, right ventrolateral prefrontal cortex (VLPFC)
      and hippocampus were more active during successful retrieval of Strong than of
      Weak associations, consistent with a role in visual associative recollection. By
      contrast, Weak trials elicited greater activation in right anterior cingulate
      cortex (ACC), which may detect conflict between the similarly familiar target and
      foil stimuli in the absence of recollection. Consistent with this interpretation,
      stronger ACC activity was associated with weaker hippocampal and stronger right
      dorsolateral PFC (DLPFC) responses. Thus, recollection of relevant visual
      associations (hippocampus and VLPFC) results in lower levels of mnemonic conflict
      (ACC) and decreased familiarity-based monitoring demands (DLPFC). These findings
      highlight the interplay between cognitive control and episodic retrieval.

PMID- 15518932
TI  - Physiological evidence for response inhibition in choice reaction time tasks.
AB  - Inhibition is a widely used notion proposed to account for data obtained in
      choice reaction time (RT) tasks. However, this concept is weakly supported by
      empirical facts. In this paper, we review a series of experiments using Hoffman
      reflex, transcranial magnetic stimulation and electroencephalography to study
      inhibition in choice RT tasks. We provide empirical support for the idea that
      inhibition does occur during choice RT, and the implications of those findings
      for various classes of choice RT models are discussed.

PMID- 15518933
TI  - The N2 in go/no-go tasks reflects conflict monitoring not response inhibition.
AB  - The functional significance of the N2 in go/no-go tasks was investigated by
      comparing electrophysiological data obtained from two tasks: a go/no-go task
      involving both response inhibition as well as response conflict monitoring, and a
      go/GO task associated with conflict monitoring only. No response was required to
      no-go stimuli, and a response with maximal force to GO stimuli. The relative
      frequency of the go stimuli (80% vs. 50%) was varied. The N2 peaked on both no-go
      and GO trials, with larger amplitudes for both signals when presented in a
      context of frequent (80%) go signals. These results support the idea that the N2
      reflects conflict monitoring not response inhibition.

PMID- 15518934
TI  - Age-related changes in antisaccade task performance: inhibitory control or
      working-memory engagement?
AB  - In antisaccade tasks, subjects are required to generate a saccade in the
      direction opposite to the location of a sudden-onset target stimulus. Compared to
      young adults, older adults tend to make more reflex-like eye movements towards
      the target, and/or show longer saccadic onset latencies on correct direct
      antisaccades. To better understand the nature of these effects of aging on
      antisaccade performance, we examined the role of age-related deficiencies in
      inhibitory control vis-a-vis age changes in the engagement of working memory.
      Inhibitory demands were manipulated using fixation-offset conditions, while
      working-memory demands were manipulated by varying memory-updating requirements.
      The results indicate that inhibitory oculomotor functions remain largely intact
      with advancing age; older adults' performance breaks down only when their limited
      working-memory capacity is taxed by increasing updating demands.

PMID- 15518935
TI  - Error-related psychophysiology and negative affect.
AB  - The error-related negativity (ERN/Ne) and error positivity (Pe) have been
      associated with error detection and response monitoring. More recently, heart
      rate (HR) and skin conductance (SC) have also been shown to be sensitive to the
      internal detection of errors. An enhanced ERN has consistently been observed in
      anxious subjects and there is some suggestion that the ERN is related to general
      negative affective experience (NA). The ERN has been source localized to the
      anterior cingulate cortex-a structure implicated in the regulation of affective,
      response selection, and autonomic resources. Thus, the findings that autonomic
      measures and affective distress are related to response monitoring are consistent
      with anterior cingulate cortex function. In the present experiment, we sought to
      evaluate more comprehensively the relationship between self-reported negative
      affect and error-related physiology in a between-groups design. Results indicate
      that high NA was associated with significantly greater ERN and error-related SCR,
      and smaller Pe. These results are discussed in terms of anterior cingulate cortex
      function, psychopathology, and response monitoring.

PMID- 15518936
TI  - A goal activation approach to the study of executive function: an application to
      antisaccade tasks.
AB  - We argue that a general control process, responsible for the activation and
      maintenance of task goals, is central to the concept of executive function.
      Failures of this process can become manifest as goal neglect: disregard of a task
      requirement even though it has been understood (Duncan, 1995). We discuss the
      results of several published and new experiments using various versions of the
      antisaccade task in order to investigate the circumstances under which goal
      neglect is likely to occur. Potentially conflicting results in the literature on
      adaptive control of saccadic eye movements are argued to be attributable to the
      extent to which different task versions elicit goal neglect. The results suggest
      an increased susceptibility to goal neglect of high-functioning older adults
      (Experiment 1) and of first-episode schizophrenia patients (Experiment 2), but
      not of patients with obsessive-compulsive disorder (Experiment 3). However, the
      degree to which such differences in susceptibility become manifest in task
      performance, is shown to be strongly influenced by manipulations of the relative
      saliency of task requirements. Theoretical and methodological implications for
      the study of executive function are discussed.

PMID- 15518937
TI  - The effects of uncertainty in error monitoring on associated ERPs.
AB  - A series of experiments were conducted to address the effect of uncertainty
      regarding performance for predicting the likelihood of a correct-response
      negativity (CRN) in addition to error-related negativity (ERN). In Study 1, 18
      healthy young adults completed letter discrimination tasks during single and dual
      attention conditions designed to manipulate response certainty. In the second
      study, the same participants completed easy and difficult tone discrimination
      tasks designed to influence stimulus certainty. In the third study, task
      difficulty was manipulated to produce different error rates without altering
      certainty. Studies 1 and 2 indicated that error and correct responses are
      processed more similarly when uncertainty is present (i.e., ERN approximately
      CRN). Furthermore, uncertainty was associated with attenuation of the ERN and
      enhancement of the CRN, consistent with an error detection hypothesis. Study 3
      indicated that task difficulty alone does not influence the ERN or likelihood of
      a CRN. These results offer support for the error detection account of the ERN and
      establish the role of uncertainty in predicting the CRN, as postulated by .

PMID- 15518938
TI  - Effects of stop-signal probability in the stop-signal paradigm: the N2/P3 complex
      further validated.
AB  - The aim of this study was to examine the effects of frequency of occurrence of
      stop signals in the stop-signal paradigm. Presenting stop signals less frequently
      resulted in faster reaction times to the go stimulus and a lower probability of
      inhibition. Also, go stimuli elicited larger and somewhat earlier P3 responses
      when stop signals occurred less frequently. Since the amplitude effect was more
      pronounced on trials when go signals were followed by fast than slow reactions,
      it probably reflected a stronger set to produce fast responses. N2 and P3
      components to stop signals were observed to be larger and of longer latency when
      stop signals occurred less frequently. The amplitude enhancement of these N2 and
      P3 components were more pronounced for unsuccessful than for successful stop
      signal trials. Moreover, the successfully inhibited stop trials elicited a
      frontocentral P3 whereas unsuccessfully inhibited stop trials elicited a more
      posterior P3 that resembled the classical P3b. P3 amplitude in the unsuccessfully
      inhibited condition also differed between waveforms synchronized with the stop
      signal and waveforms synchronized with response onset whereas N2 amplitude did
      not. Taken together these findings suggest that N2 reflected a greater
      significance of failed inhibitions after low probability stop signals while P3
      reflected continued processing of the erroneous response after response
      execution.

PMID- 15518939
TI  - Additive factors analysis of inhibitory processing in the stop-signal paradigm.
AB  - This article reports an additive factors analysis of choice reaction and
      selective stop processes manipulated in a stop-signal paradigm. Three experiments
      were performed in which stimulus discriminability (SD) and stimulus-response
      compatibility (SRC) were manipulated in a factorial fashion. In each experiment,
      the effects of SD and SRC were assessed first for going and next for stopping.
      Two experiments yielded the anticipated additive relation between SD and SRC for
      going but stopping appeared to be insensitive to the SD manipulation. Increasing
      the SD demands in the third experiment by using a different display resulted in a
      significant (over-additive) interaction between SD and SRC for going and a non
      significant (under-additive) interaction for stopping. The pattern of results
      that emerged from this set of experiments was interpreted to suggest that going
      and stopping are both similar and different. They are similar in that distinct
      stages can be identified in both going and stopping but they are also different,
      as selective stopping seems to be less sensitive to discrimination manipulations
      relative to going.

PMID- 15518940
TI  - Errors without conflict: implications for performance monitoring theories of
      anterior cingulate cortex.
AB  - Recent theories of the neural basis of performance monitoring have emphasized a
      central role for the anterior cingulate cortex (ACC). Replicating an earlier
      event-related potential (ERP) study, which showed an error feedback negativity
      that was modeled as having an ACC generator, we used event-related fMRI to
      investigate whether the ACC would differentiate between correct and incorrect
      feedback stimuli in a time estimation task. The design controlled for response
      conflict and frequency and expectancy effects. Although participants in the
      current study adjusted their performance following error feedback, we did not
      observe error feedback-evoked ACC activity. In contrast, we did observe ACC
      activity while the same subjects performed the Stroop task, in which an area of
      the ACC activated during both conflict and error trials. These findings are
      inconsistent with previous dipole models of the error feedback negativity, and
      suggest the ACC may not be involved in the generation of this ERP component.
      These results question involvement of the ACC in the detection of errors per se
      when controlling for conflict.

PMID- 15518941
TI  - [Adipose tissue, plastic and reconstructive surgery: come back to sources].
AB  - The adipose tissue represents a large amount of adult tissue. For long time, it
      was considered as a filling tissue and used in plastic and reconstructive
      surgery. It was always studied for its main involvement in energy metabolism and
      energy disorders as diabetes and obesity. More recently, its endocrine functions
      emerged and thus play a key role in many physiological functions as inflammation
      and immunity. The presence of preadipocytes throughout life was demonstrated
      using primary culture technology from cells derived from adipose tissue. In
      recent papers, cells derived from adipose tissue were used for haematopoiesis,
      vascularisation or skeletal muscle recovery. Differentiation into functional
      cardiomyocytes, osteoblasts and neural cells was obtained in vitro. These
      spectacular data, the fact that adipose tissue is easy to sample and the
      possibility to create cell or tissue banks open numerous and promising
      perspectives in regenerative medicine.

PMID- 15518942
TI  - [Historical review of the use of adipose tissue transfer in plastic and
      reconstructive surgery].
AB  - Use of adipose tissue transfer in plastic and reconstructive surgery is not new,
      and has been the subject of numerous studies. Transfer of autologous adipose
      tissue was reported for the first time at the end of the 19th century. Ideas and
      techniques have greatly changed during the last century. Adipocyte transfer has
      attracted renewed interest in recent years, due in particular to the development
      of Lipostructure by Coleman, who introduced a procedure based on strict
      methodology and the use of specific material. The history of adipose tissue
      transfer is retraced through the works of various authors and briefly recounted
      by highlighting the major landmarks of its advance. The evolution of ideas and
      techniques can be divided into three periods. The period before the introduction
      of lipoaspiration was termed "open surgery", when adipose tissue was harvested by
      surgical excision. The next period is that following the discovery of
      lipoaspiration, called the "unrefined" period, during which adipose tissue was
      obtained by aspiration and reinjected without preparation. During the third
      period, following the works of Coleman, the adipose tissue now undergoes non
      traumatic refinement before grafting; this period is called "non-traumatic
      refined". Various studies have shown that this technique causes little damage to
      the cells and have demonstrated survival of the tissue transferred. Discovery of
      the developmental capacities of the various lineages from a mesodermal stem cell,
      and in vitro culture of these cells, opens up new research perspectives and
      clinical applications. From this precursor cell, adipocytes, osteoblasts,
      chondrocytes, myocytes and neurone-like cells can be developed. The future of
      autologous reconstruction appears promising.

PMID- 15518943
TI  - [The effect of different factors on the survival of transplanted adipocytes].
AB  - Most authors supported the theory of adipocyte survival. The viability of these
      cells has been demonstrated by various experimental clinical, radiological and
      biochemical studies. After a review of the literature, the authors report the
      various factors, which influence the survival of the transplanted adipocytes.
      These factors are presented according to their chronology in the operative
      procedure. The techniques used are very diverse. The reference technique chosen
      is that described by Coleman (Lipostructure). The following factors are studied:
      type of anaesthesia, infiltration, donor site of adipose tissue, method of
      harvesting, method of refining adipose tissue, anabolic complements, receiving
      site, reinjection technique, number of grafting sessions, freezing of adipose
      tissue and complementary postoperative treatments. It seems imperative that each
      phase of the operative procedure should be carried out without damage to the
      adipocytes, in particular their harvesting, refining and reinjection. All the
      other factors studied require comparative analysis in order to demonstrate their
      true importance. This opens up various directions of research aiming to improve
      the survival of the transplanted adipocytes.

PMID- 15518944
TI  - [Clinical evaluation of structural fat tissue graft (Lipostructure) in volumetric
      facial restoration with face-lift. About 100 cases].
AB  - INTRODUCTION: Adipose tissue has been used for volume restoration for over a
      century. Coleman's Lipostructure is a recent procedure for adipocyte transfer,
      based on strict methodology and the use of specific material. Our aim in this
      work is to provide an answer to several questions: what is the place of this
      technique in the restoration of facial volumes? Do aesthetic subunits have an
      impact on the result? MATERIAL AND METHODS: This retrospective study concerned
      100 patients who had undergone volumetric facial restoration with face-lift and
      Lipostructure. A five-member jury carried out subjective evaluation through a
      questionnaire sent to the patients, and objective evaluation by assessment of pre
      and postoperative photographs. RESULTS: Mean time since surgery was 15 months.
      Overall patient satisfaction was 82% with a mean score of 15/20 on subjective
      evaluation and of 13.3/20 on objective evaluation. The results differed
      significantly according to the facial aesthetic subunit involved, the best
      results being obtained in the malar region and the cheek, and the least
      satisfactory in the upper and lower lips. This technique has few drawbacks.
      Prolonged oedema is the only complication (8%). CONCLUSION: We consider that at
      the present time Lipostructure is the best means of restoring facial volume. It
      is a simple, effective and reproducible technique. Its application in all fields
      of plastic surgery is an essential adjunct to our specialty.

PMID- 15518946
TI  - [Injectable collagen].
AB  - The aim of this paper is to evaluate the so-called "American" injectable
      collagen, produced since 1975 by Collagen Corporation. Main interest of that work
      concerns an actual follow-up on millions of patients, treated since 25 years,
      with more than 280 clinic studies published throughout international literature.
      Everybody knows that--in human therapeutic--a very long follow-up and a great
      number of patients is a warranty for a complete security. This Collagen is
      natural, extracted from bovine dermis; this is the first "true cosmetic drug".
      Therefore, rigorous practice conditions have to be respected.

PMID- 15518947
TI  - [Soft tissue filling with hyaluronic acid].
AB  - PHYSIOLOGY AND PHARMACOLOGY: Hyaluronan was discovered by Karl Meyer in 1934 in
      the vitreous humor of cattle eye. Hyaluronic acid, (AH), is a natural
      polysaccharide and a ubiquitous component of the extra cellular matrix. It is
      largely biocompatible and has a short half life. In the early 1990's, preceded by
      the use of bovine collagen, AH started to be employed in the fields of
      Dermatology and Plastic Surgery; currently it is a major intervention product in
      both soft tissue augmentation and facial volume loss treatments. Often well
      tolerated, AH, has high water retention properties and is an effective tissue
      volumizer. Industry first attempted to extract AH from rooster comb, then through
      bacterial fermentation and succeeded in increasing its lifespan by cross linking.
      However, industrially produced AH can contain residues from the manufacturing
      process. It thus appears critical to us to be informed of the process used in
      manufacturing AH including the reticulant utilized. Manufacturers should be
      legally required to publish this data as well as to conduct physiochemical follow
      up studies over the short, mid and long terms. LEGAL CONSIDERATIONS: In Europe,
      CE marking is a prerequisite to market injectable products. However, a CE marking
      does not necessarily imply that the product's efficacy and side effects have been
      assessed objectively in clinical studies. However, this marking is expected to
      fall into line with the US legislation, where the marketing of any medicinal
      product is subject to FDA approval, based on comprehensive animal and clinical
      studies and on more systematic and better centralised side effect reporting. We
      have examined most of the products used in Europe and internationally in 2004,
      whether of animal or bacterial origin, reticulated or non-reticulated, and used
      to restore, increase volume or as a product vector. Before injecting these
      products, it is essential to have a thorough understanding of their absolute and
      relative contraindications and anaesthetic requirements, differences between
      types of wrinkles to fill in and indicated techniques, differences between
      concerned regions or tissues, and the impact of associated cosmetic treatments.
      These resorbable injectable products have mild and, more importantly, short-lived
      side effects. However, in patients with a relative contraindication, a double
      test is justified, as allergic reactions are known to occur in 1 to 3% of
      patients. It is also advisable not to inject HA in a site previously injected
      with a non-resorbable product. More precise statistics on results and side
      effects based on double-blind randomised studies are still wanting, due to the
      lack of legal requirement and effective centralisation of data. Therefore, all
      side effects must be reported to improve our knowledge as well as the safety of
      injections. CONCLUSION: Although their duration of effect is limited, HA products
      are the most commonly used fillers, before collagens. Many questions have yet to
      be answered, but they produce very significant results in filling procedures.
      Both clinicians and patients praise these products for their tolerance,
      resorbable nature, and limited side effects.

PMID- 15518948
TI  - [Slowly absorbable and non absorbable injectable products].
AB  - Products which are non absorbable or slowly absorbable make the correction of
      facial wasting of any origin possible. These highly efficient products are
      unfortunately sometimes responsible for complications or even undesirable after
      effects. In order to avoid this the following are necessary: clinical and
      histological analysis of facias granulomas, a proposal for guidelines for their
      use which would predict in situ tolerance.

PMID- 15518949
TI  - [Facial rejuvenation: rationale use of lasers and thermal systems].
AB  - The methods additional or substitution for the surgery of facial skin ageing are
      dramatically rising before 40 years. These methods are addressed more to the
      wrinkles and others signs of aging skin. They can constitute a door of entry in
      the aesthetic treatments and needs a professional approach. These noninvasive
      methods (within the meaning of the incision) can present complications this the
      more so as the tendency is with the vulgarizing and with under considerations of
      the initial diagnosis and the treatment itself. The devices of thermal effects
      consist of lasers, pulsed flashlamps and radiofrequency. The objective of this
      development is to consider the bonds, which link the initial diagnosis and the
      proposal for a treatment by considering side effects and complications of each
      method.

PMID- 15518950
TI  - [Complications of laser facial resurfacing].
AB  - Laser resurfacing is a burn of the superficial skin layers: it's a controlled
      burn in its depth, that can destroy epidermis and the dermis superficial part,
      but not deeper for avoiding healing complications. All complications and the
      normal postoperative follow-up can be explained by the fact that laser
      resurfacing is a burn of the dermis and epidermis, with the destruction, partial
      or total, of their components. It's essential to understand the normal
      postoperative process and complications to avoid them and to treat them in the
      beginning. Infection, persistent erythema, pigmentation troubles like
      hyperpigmentation or depigmentation and demarcation surrounding the resurfacing
      area, healing troubles like hypertrophic scarring, keloids, excess of skin
      retraction are the main complications. Careful preoperative explanation of laser
      resurfacing follow-up will help the patient adjust more easily to postoperative
      care.

PMID- 15518951
TI  - [Frontal muscular balance and botulinum toxin].
AB  - A good knowledge of the anatomy of the muscles of upper third of the face and
      their function, a good understanding of the famous Frontal Muscular Balance, to
      consider the anatomic and histological modifications induced by ageing in the
      cutaneous layer and the muscular function of the underlying "peaucier muscles",
      are essential for a better approach and for an easy and safe use of botulinum
      toxin, remarkable product, and for avoiding its operator-dependent risks.

PMID- 15518952
TI  - [Functional facial analysis after botulin on toxin injection].
AB  - As usual, the face at rest is analysed before btx injection. But the interest of
      the analysis of the face dynamically, in a functional way, with the help of the
      palpation, is demonstrated. A key point is to decide to favor the high position
      of the highbrow more than to totally fade the frontal wrinkles. To perform this,
      a new functional segmentation of the frontalis muscle is described. The role of
      the procerus muscle as antagonist of the frontalis muscle, inferior medial part,
      is explained. To elevate the medium third of the eyebrow, the lateral part of the
      corrugator muscle is injected with a specific technique. This technique decreases
      the risk of weakening the overlying frontalis muscle and the underlying levator
      palpebrae muscle. To achieve a higher elevation of the eyebrow tail, and to
      totally fade the upper and medium crow's foot, different points of injection on
      the lateral orbital rim are described, without the risk of migration to the oculo
      motor muscles. Fading the tear trough with the injection of the superior malar
      part of the orbicularis oculi muscle is explained. Thanks to the use of the
      functional analysis of the face and to the comprehension of the fabulous
      possibilities of the botulinum toxin A, it is now justified to switch from a
      "ready to wear" way of injection to a "haute couture" way, that is to say adapted
      to each patient.

PMID- 15518953
TI  - [Botulinum toxin and wrinkles: few side effects and effective combining
      procedures with other treatments].
AB  - Chemical denervation, through the biologic effect of botulinum toxin, provides a
      very effective, low risk, lasting treatment for hyperkinetic wrinkles, mainly of
      the upper face. Patients with such rhytides, when treated with surgical myotomies
      or other alternative medical treatments, are at greater risk and with potentially
      less lasting results. Botulinum toxin has been widely used for the last 20 years
      in many areas of medicine. It has been used for 13 years in dermatology and
      plastic surgery, without important complications or sequellae. Any complications
      appear to be reversible. In these two specialties, with the minute quantities
      (units) and volume of material injected, complications are infrequent; some of
      them are now anecdotal. The only main complication from a cosmetic point of view
      is blepharoptosis, which is more and more rare. Because of a better anatomical
      knowledge of the affected muscles, and our improved technique, risks are greatly
      reduced. In our two latest multicenter studies on glabellar wrinkles, between
      2002 and 2004, we saw no blepharoptosis. Conversely, in case of dynamic wrinkles
      associated with muscle, fat, and skin relapse, and/or deep furrows, only surgical
      procedures and/or other surface treatments are effective. Botulinum toxin
      injections are not meant to replace upper, mid, or mandibular face and neck
      lifts; indeed, botulinum toxin injections may optimize results from these
      surgical procedures. These injections play a fundamental process in producing
      long lasting results. The current and future evolution, in cosmetic surgery, is
      toward full achieved, but focused, natural, and minimally invasive surgical
      procedures in combination with effective and minimal risk techniques such as the
      botulinum toxin injections. To optimize the effect of the medical procedures,
      botulinum toxin should be injected three weeks before surgery. In addition
      botulinum toxin injections may optimize and prolong the effect of the surface
      procedures, as lasers, peels and fillers. This medicosurgical combination is one
      of the examples that best describes the evolution of plastic and aesthetic
      surgery in 2004.

PMID- 15518954
TI  - Roles of the mammalian subventricular zone in cell replacement after brain
      injury.
AB  - The subventricular zones (SVZs) are essential sources of new cells in the
      developing brain and remnants of these germinal zones persist into adulthood. As
      these cells have the capacity to replenish neurons and glia that are turning
      over, many investigators have assessed the SVZ's role in replacing neural cells
      eliminated by brain injuries. A review of the literature reveals that the
      progenitors within the SVZs are vulnerable to chemical, radiation and ischemia
      induced damage, whereas the neural stem cells are resilient. With moderate
      insults, the SVZ can recover, but it cannot recover after more severe injury.
      Thus, the vulnerability of these cells has important ramifications when
      considering therapeutic interventions for the treatment of brain tumors and for
      the prospect of recovery after ischemia. The cells of the perinatal and adult SVZ
      not only have the capacity to replenish their own numbers, but they also have the
      capacity to replace neurons and glia after ischemic and traumatic brain injuries.
      Moreover, the mechanisms underlying these regenerative responses are beginning to
      be revealed. By reviewing, comparing and contrasting the responses of the SVZs to
      different injuries, our goal is to provide a foundation from which current and
      future studies on the potential of the SVZs for cell replacement can be
      evaluated.

PMID- 15518955
TI  - The rhinal cortices: a wall of inhibition between the neocortex and the
      hippocampus.
AB  - Anatomical data indicate that the parahippocampal region, comprised of the
      perirhinal (PRC), postrhinal (POR) and entorhinal (ERC) cortices, is an essential
      link between neocortex and hippocampus. Lesion studies demonstrated that memory
      functions previously ascribed to the hippocampus depend on the integrity of the
      rhinal cortices. This review will consider recent data suggesting that the ERC
      and PRC, far from being passive relay stations, actively gate impulse traffic
      between neocortex and hippocampus, because they are endowed with a powerful
      intrinsic inhibitory system. It is proposed that the cross-talk between PRC and
      ERC is not organized to unrestrictedly transfer information, but to select
      relevant inputs. The implication of these new evidences for the propagation of
      epileptiform activity will be considered.

PMID- 15518956
TI  - On dendrites in Down syndrome and DS murine models: a spiny way to learn.
AB  - Since the discovery in the 1970s that dendritic abnormalities in cortical
      pyramidal neurons are the most consistent pathologic correlate of mental
      retardation, research has focused on how dendritic alterations are related to
      reduced intellectual ability. Due in part to obvious ethical problems and in part
      to the lack of fruitful methods to study neuronal circuitry in the human cortex,
      there is little data about the microanatomical contribution to mental
      retardation. The recent identification of the genetic bases of some mental
      retardation associated alterations, coupled with the technology to create
      transgenic animal models and the introduction of powerful sophisticated tools in
      the field of microanatomy, has led to a growth in the studies of the alterations
      of pyramidal cell morphology in these disorders. Studies of individuals with Down
      syndrome, the most frequent genetic disorder leading to mental retardation, allow
      the analysis of the relationships between cognition, genotype and brain
      microanatomy. In Down syndrome the crucial question is to define the mechanisms
      by which an excess of normal gene products, in interaction with the environment,
      directs and constrains neural maturation, and how this abnormal development
      translates into cognition and behaviour. In the present article we discuss mainly
      Down syndrome-associated dendritic abnormalities and plasticity and the role of
      animal models in these studies. We believe that through the further development
      of such approaches, the study of the microanatomical substrates of mental
      retardation will contribute significantly to our understanding of the mechanisms
      underlying human brain disorders associated with mental retardation.

PMID- 15518957
TI  - A collection of papers presented at the Annual Symposium of the Mary Kay O'Connor
      Process Safety Center, Texas A&M University, College Station, Texas, USA. 28-29
      October 2003.

PMID- 15518958
TI  - Learning from experience.
AB  - Some process accidents and the actions needed to prevent them occurring again are
      described. They illustrate the following points: Some investigators are too eager
      to recommend changes in instructions or better observation of them than to look
      for ways of removing hazards or for changes in design that will make an accident
      less likely. Some people fail to calculate the effects of changes or the time
      required for them to take place. Facts that are well known in one industry or
      company may be unknown in another. The incidents have been chosen because of
      their value as learning experiences.

PMID- 15518959
TI  - Drivers of accident preparedness and safety: evidence from the RMP Rule.
AB  - This paper provides an overview of recent results derived from the accident
      history data collected under 112(r) of the Clean Air Act Amendments (the Risk
      Management Program (RMP) Rule) covering the period 1994-2000, together with a
      preliminary assessment of the effectiveness of the RMP Rule as a form of
      Management System Regulation. These were undertaken at the University of
      Pennsylvania by a multi-disciplinary team of economists, statisticians and
      epidemiologists with the support of the US Environmental Protection Agency and
      its Office of Emergency Prevention, Preparedness and Response (OEPPR, formerly
      CEPPO). Section 112(r) of the Clean Air Act Amendments of 1990 requires that
      chemical facilities in the US that had on premises more than specified quantities
      of toxic or flammable chemicals file a 5-year history of accidents. The initial
      data reported under the RMP Rule covered roughly the period from mid-1994 through
      mid-2000, and provided details on economic, environmental and acute health
      affects resulting from accidents at some 15,000 US chemical facilities for this
      period. This paper reviews research based on this data. The research is in the
      form of a retrospective cohort study that considers the statistical associations
      between accident frequency and accident severity at covered facilities (the
      outcome variables of interest) and a number of facility characteristics (the
      available predictor variables provided by the RMP Rule), the latter including
      such facility characteristics as size, hazardousness, financial characteristics
      of parent company-owners of the facility, regulatory programs in force at the
      facility, and host community characteristics for the surrounding county in which
      the facility was located, as captured in the 1990 Census. Among the findings
      reviewed are: (1) positive associations with (a measure of) facility
      hazardousness and accident, injury and economic costs of accidents; (2) positive
      (resp., negative) associations between accident propensity and debt-equity ratios
      (resp., sales) of parent companies; (3) several interrelated associations between
      accident propensity and regulatory programs in force; and (4) strong associations
      between facility hazardousness, facility locations decisions, observed accident
      frequencies and community demographics.

PMID- 15518960
TI  - Making the business case for process safety using value-at-risk concepts.
AB  - An increasing emphasis on chemical process safety over the last two decades has
      led to the development and application of powerful risk assessment tools. Hazard
      analysis and risk evaluation techniques have developed to the point where
      quantitatively meaningful risks can be calculated for processes and plants.
      However, the results are typically presented in semi-quantitative "ranked list"
      or "categorical matrix" formats, which are certainly useful but not optimal for
      making business decisions. A relatively new technique for performing valuation
      under uncertainty, value at risk (VaR), has been developed in the financial
      world. VaR is a method of evaluating the probability of a gain or loss by a
      complex venture, by examining the stochastic behavior of its components. We
      believe that combining quantitative risk assessment techniques with VaR concepts
      will bridge the gap between engineers and scientists who determine process risk
      and business leaders and policy makers who evaluate, manage, or regulate risk. We
      present a few basic examples of the application of VaR to hazard analysis in the
      chemical process industry.

PMID- 15518961
TI  - The role of adverse weather conditions in acute releases of hazardous substances,
      Texas, 2000-2001.
AB  - High winds, flooding, lightning, and other phenomena associated with adverse
      weather can cause power failures, equipment damage, and process upsets resulting
      in chemical releases. Of the 5000 events in Texas that were reported to the
      Hazardous Substances Emergency Events Surveillance (HSEES) system during 2000
      2001, adverse weather conditions contributed to 110 (2%) events. Rain was the
      most frequent adverse weather condition. Most events to which adverse weather
      conditions contributed occurred during June or September; these months correspond
      with the high temperature and hurricane season in Texas. Most events occurred in
      coastal counties with large numbers of industrial facilities. Three industries
      reported the majority of events: industrial and miscellaneous chemicals
      manufacturing; petroleum refining; and plastics, synthetics, and resin
      manufacturing. Power failures were associated more often with adverse weather
      related events than with nonweather-related events. Releases occurred most
      commonly from ancillary process equipment and process vessels. Events associated
      with adverse weather-related conditions involved nine victims. System and process
      design improvements, such as improved backup power generation and redesigned
      secondary containment systems, could be explored to reduce the potential negative
      effects of severe weather.

PMID- 15518962
TI  - Lessons learned from hazardous chemical incidents--Louisiana Hazardous Substances
      Emergency Events Surveillance (HSEES) system.
AB  - Since 2001, the Louisiana Department of Health and Hospitals (LDHH) has
      participated in the Hazardous Substances Emergency Events Surveillance (HSEES)
      system. In 2001, there were 815 events qualified for HSEES surveillance. Data for
      each event was gathered and analyzed. During these hazardous substances events,
      there were 1164 chemicals released resulting in injuries to 63 people, most with
      respiratory system irritation. Even though more people were injured in fixed
      facility events, injuries were more likely to result from transportation-related
      events. The quantity and frequency of hazardous substance releases do not always
      positively correlate with the number of injuries sustained during those releases.
      A higher percentage of "Rail" transport events was observed in Louisiana when
      compared with other HSEES states. By collecting and analyzing more data and
      disseminating results to the public, it is expected that further adverse public
      health consequences from hazardous releases/spills in Louisiana can be reduced
      and/or minimized.

PMID- 15518963
TI  - New York hazardous substances emergency events surveillance: learning from
      hazardous substances releases to improve safety.
AB  - Since 1993, the New York State Department of Health, funded by the Agency for
      Toxic Substances and Disease Registry, has collected data about non-petroleum
      hazardous substances releases through the Hazardous Substances Emergency Events
      Surveillance (NYHSEES) project. This study investigates risk factors for
      hazardous substances releases that may result in public health consequences such
      as injury or reported health effects. The 6428 qualifying events that occurred
      during the 10-year-period of 1993-2002 involved 8838 hazardous substances, 842
      evacuations, more than 75,419 people evacuated, and more than 3120 people
      decontaminated. These events occurred both at fixed facilities (79%) and during
      transport (21%). The causative factors most frequently contributing to reported
      events were equipment failure (39%) and human error (33%). Five of the 10
      chemicals most frequently associated with injuries were also among the 10
      chemicals most frequently involved in reported events: sulfuric acid,
      hydrochloric acid, ammonia, sodium hypochlorite, and carbon monoxide. The
      chemical categories most frequently associated with events, and with events with
      adverse health effects were volatile organic compounds (VOCs) and solvents, and
      acids. Events with releases of hazardous substances were associated with injuries
      to 3089 people including employees (37%), responders (12%), the general public
      (29%) and students (22%). The most frequently reported adverse health effects
      were respiratory irritation, headache, and nausea or vomiting. Most of the
      injured were transported to the hospital, treated, and released (55%) or treated
      at the scene (29%). These data have been used for emergency response training,
      planning, and prevention activities to reduce morbidity and mortality from future
      events.

PMID- 15518964
TI  - Evaluation of 1,3-butadiene dimerization and secondary reactions in the presence
      and absence of oxygen.
AB  - Thermal stability evaluation of exothermic chemical reactions is of great
      importance to the safer design and operation of chemical processes. Dominant
      reaction stoichiometries and their thermochemistry parameters are key elements in
      the evaluation process. Identification of significant reaction pathways under
      possible process conditions will lead to an understanding of the overall
      thermodynamic and kinetic behavior. The kinetics of 1,3-butadiene (BD) is an
      excellent example of conjugated dienes that undergo addition reactions. At
      elevated temperatures, 1,3-butadiene monomers can dimerize exothermally, and as
      temperature increases, secondary exothermic reactions will take place. The very
      high temperature and pressure rates that these reactions can attain may lead to a
      reaction runaway or even a thermal explosion. BD is a vapor at ambient
      conditions, usually stored as a pressurized liquid, and is a carcinogen, so the
      experimental evaluation is potentially difficult and hazardous. In this paper,
      the thermal stability of BD is evaluated. Dimerization and other secondary
      reactions are investigated by experimental thermal analysis using an automatic
      pressure adiabatic calorimeter (APTAC), by theoretical computational quantum
      chemistry methods, and empirical thermodynamic-energy correlations. A theoretical
      approach is conducted to predict some of the BD reaction behavior. Results are
      compared to other literature data obtained using different experimental methods.

PMID- 15518965
TI  - Calorimetric study on the decomposition of hydroxylamine in the presence of
      transition metals.
AB  - Hydroxylamine (HA), hydroxylamine chloride (HAC1), and hydroxylamine nitrate
      (HAN) were each mixed with aqueous solutions of Cr3+, Cr6+, Mn7+, Co2+, Co3+, and
      Cu2+, and their heat flow profiles were monitored by a small-scaled reaction
      calorimeter, SuperCRC. These mixing tests demonstrated that HA was less reactive
      than HACl and HAN with Mn7+ and Cr6+. Their UV-vis spectra confirmed that the
      substrates reacted when Mn7+ and Cr6+ were reduced. HA was more reactive with
      Cu2+ than HAC1 and HAN and exhibited the highest reactivity among the three
      substrates with regard to metals in the intermediate oxidation states: Cr3+,
      Co3+, and Co2+. During the reaction of HA and Co3+, an induction period was
      observed. All exothermic reactions were accompanied by precipitation or a change
      in the UV-vis spectra.

PMID- 15518966
TI  - Chemical reactivity assessments in R&D.
AB  - The evaluation of reactive chemical hazards at the pilot and manufacturing scale,
      using laboratory testing, is increasingly used and has been well documented.
      However, reactive chemical hazard evaluation at the R&D scale presents special
      challenges. The typical hazard testing program requires a significant amount of
      sample, often takes time (>3 days) to complete, and is can be quite costly. On
      the other hand, the synthesis of new molecules in the R&D environment often
      produces only a few grams, occurs quickly (<2 days), may only happen once and
      many synthetic reactions may be carried out before a suitable candidate for scale
      up will be found. However, with each new synthesis there is the risk of injury,
      possibly serious or fatal, caused by unexpected and maybe violent reactivity.
      While it may not be possible at the R&D stage of product development to define
      the critical limits of temperature, pressure, concentration, and safe dosing
      rates of processes it is possible to identify the potential hazards of the
      planned synthesis. This paper describes a staged approach for chemical reactivity
      hazard evaluation and assessment applicable to an R&D environment. We will
      describe these initial phases of the R&D hazard evaluation process that rely on
      only data that can be obtained from the open literature. We will also indicate
      how the need for additional assessments can be determined from this initial
      hazard review.

PMID- 15518967
TI  - The reactivity of 1,3-butadiene with butadiene-derived popcorn polymer.
AB  - Adiabatic calorimetry performed on butadiene-derived popcorn polymer samples from
      industrial facilities has revealed exothermic behavior accompanied by non
      condensible gas production, indicative of possible decomposition, at elevated
      temperatures. In the presence of low concentrations of 1,3-butadiene, reactivity
      is observed at temperatures of 60-70 degrees C; that is, 20-30 degrees C below
      those usually seen for butadiene alone. Once the butadiene is consumed, the
      reaction behavior reverts to that of the popcorn polymer alone. At higher
      butadiene concentrations, the low temperature reaction persists, eventually
      merging with typical butadiene behavior. The butadiene reactivity with popcorn
      polymer is attributed to polymerization reaction at free radical sites in the
      popcorn polymer. Different popcorn polymer samples exhibit distinct extents of
      reactivity, presumably depending on the nature and concentration of the free
      radical sites and the structure of the material. Uninhibited butadiene exposed to
      100 psia air, which may act to generate peroxide species, shows a small,
      additional exotherm around 50-80 degrees C. Contact of butadiene with lauroyl
      peroxide, providing free radicals upon decomposition, generates an exotherm at
      temperatures as low as 60 degrees C.

PMID- 15518969
TI  - Use of ARC in screening for explosive properties.
AB  - The use of a modified version of the accelerating rate calorimeter (ARC) as a
      screening method for the explosive properties of chemicals has been investigated.
      Definitive tests for classifying energetic chemicals for transportation are
      provided by UN Recommendations [United Nations, Recommendations on the Transport
      of Dangerous Goods, Manual of Tests and Criteria, third revised ed., 1999].
      Recently, decomposition energy screening criteria were added to the
      recommendations, however, maximum rate of pressure rise in a closed vessel may
      provide a less conservative, more accurate screen. Pressure rate data for organic
      chemicals are compared to the UN test results. Preliminary screens are suggested
      to minimize the need for the larger scale, more expensive, and time-consuming UN
      recommended testing. Results from this method are compared to those from
      published mini-autoclave data [M.W. Whitmore, G.P. Baker, J. Loss Prev. Process
      Ind. 12 (1999) 207-216]. Further work is planned to expand the range of chemical
      classes tested and to specify acceptable, conservative screening criteria.

PMID- 15518968
TI  - Study of condition-dependent decomposition reactions; Part I. The thermal
      behaviour and decomposition of 2-nitrobenzoyl chloride.
AB  - The risks associated with batch processing in the manufacture of chemicals and
      pharmaceuticals via highly exothermic reactions are of special interest due to
      the possibility of runaway reactions. o-Nitrated benzoyl chlorides are
      intermediates in the production of agrochemicals and are produced via the
      reaction of o-nitrated carboxylic acids with thionyl chloride in a solvent
      mixture. ortho-Nitrated acyl chlorides have exploded violently on attempted
      distillation on numerous occasions. An inadequate investigation of the process
      prior to large-scale operation is the most likely cause. Here we present
      preliminary results of studies on the decomposition of 2-nitrobenzoyl chloride.
      This study has revealed that the decomposition reaction is strongly condition
      dependent. The heating rate of the sample plays a preponderant role in the course
      of the decomposition reaction. That renders the interpretation of differential
      scanning calorimetry (DSC) or adiabatic calorimetry measurements, which are
      routinely used to assess the thermochemistry and safety of the large-scale
      reactions, problematic. Following this on-going study, we report here key
      features of the system that have been identified.

PMID- 15518970
TI  - Testing strategy for classifying self-heating substances for transport of
      dangerous goods.
AB  - A testing strategy for the classification of self-heating substances for
      transport of dangerous goods is proposed. The strategy was developed based on the
      tests described and correlations used in the UN Recommendations. It was
      demonstrated that the value of activation energy of the exothermic reaction has a
      significant impact on the extrapolation of test results with regard to different
      container sizes and temperatures. Based on a combination of the Grewer Oven test
      screening, the 25 mm cube test at 140 degrees C, and the determination of the
      activation energy of a specific material, a flowchart is presented for
      classifying chemicals as self-heating. The presented approach allows predicting
      chemical stability in large containers more accurately and eliminates the need to
      perform hazardous large-scale tests of energetic chemicals in a laboratory.

PMID- 15518971
TI  - Effect of droplet size distribution on reaction heat in a liquid-liquid
      heterogeneous reaction process.
AB  - In heterogeneous liquid-liquid reaction processes, explosions have been reported.
      An aim of this study is to simulate the accident stories, which might be caused
      by inappropriate mixing conditions in the heterogeneous reaction process. The
      reaction of water-insoluble anhydride and water was selected as a model process.
      The experimental trend data of droplet size with agitation in a batch reactor
      were fitted to an empirical equation. The good fittings show the applicability of
      the equation in our reaction conditions.

PMID- 15518972
TI  - Learning from what went wrong--two case studies.
AB  - Safer design of process equipment can protect against unexpected events. Two case
      studies involving the design of a process vessel and the subsequent events will
      be reviewed. One case study will show how the original design minimized equipment
      damage from an operational error, and how additional safeguards will prevent
      recurrence. The second case study will show that over time small process changes
      can lead to an unexpected chemical reaction that results in a vessel rupture. We
      will also cover the additional safeguards added to prevent recurrence.

PMID- 15518973
TI  - Chlorine transfer hose failure.
AB  - On the morning of 14 August 2002, a 1 in. transfer hose used in a rail tank car
      unloading operation at DPC Enterprises, near Festus, Missouri, catastrophically
      ruptured and initiated a sequence of events that led to the release of 48,000
      pounds of chlorine--a toxic gas--into neighboring areas. The facility repackages
      bulk dry liquid chlorine into 1 ton containers and 150 pound cylinders for
      commercial, industrial, and municipal use in the St. Louis metropolitan area.
      Fortunately, the wind direction on the day of the release limited the effects of
      the chlorine plume on the surrounding community. However, 63 people sought
      hospital treatment due to exposure, and hundreds of others were affected by the
      release (the community was advised to shelter-in-place for 4 h, and traffic was
      halted on Interstate 55 for 1.5 h). The US Chemical Safety and Hazard
      Investigation Board (CSB) investigated this incident for the following reasons:
      This paper presents the lesson-learned from this incident to help prevent similar
      occurrences. This paper is based on US Chemical Safety and Hazard Investigation
      Board Report Number 2002-04-I-MO, which was approved by the Board on 1 May 2003.
      This paper has not been independently approved by the Board and is published for
      general informational purposes only. Every effort has been made to accurately
      present the contents of the Board-approved report in this paper. Any material in
      the paper that did not originate in the Board-approved report is solely the
      responsibility of the author and does not represent an official finding,
      conclusion, or position of the Board. A complete copy of the Board investigation
      report upon which this paper is based is available on the CSB website at
      "Completed Investigations."

PMID- 15518974
TI  - Whose fault is it anyway? A practical illustration of human factors in process
      safety.
AB  - Major process accidents have typically occurred not through a single failure, but
      through a combination of events, some of which had contributors from past actions
      and failures (latent or unrevealed failures). People are integral and key
      features of business systems; therefore systems, tools, and equipment should be
      designed with the potential capabilities and limitations of people in mind. This
      paper demonstrates the benefits of using human factors approaches to improve
      system safety and reliability. Practical examples from past experience are quoted
      and a framework for human error prediction is described. Guidance is given on the
      practicalities of deriving recommendations from these types of studies.

PMID- 15518975
TI  - Explosion caused by flashing liquid in a process vessel.
AB  - An explosion occurred at a polyvinyl chloride (PVC) resin manufacturing plant.
      The explosion originated at an atmospheric storage vessel when it received a
      slurry discharge from a suspension polymerization reactor. The pressure rise
      caused by the uncontrolled flashing of superheated liquid vinyl chloride resulted
      in the complete separation of the roof from the tank shell. A cloud of vinyl
      chloride vapor was released and ignited resulting in a vapor cloud explosion. The
      accident caused significant property damage but no serious injuries. An
      investigation was conducted to determine the causes of the accident. It was
      discovered that the facility had experienced numerous overpressure incidents in
      the atmospheric storage vessels used as slurry tanks. Many of these incidents
      resulted in modest structural damage to these slurry tanks. It was determined by
      Exponent that the rapid flashing of residual liquid monomer present in the
      product slurry stream caused the earlier overpressure incidents. The facility
      operator did not adequately investigate or document these prior overpressure
      events nor did it communicate their findings to the operating personnel. Thus,
      the hazard of flashing liquid vinyl chloride was not recognized. The overpressure
      protection for the slurry tanks was based on a combination of a venting system
      and a safety instrumentation system (SIS). The investigation determined that
      neither the venting system nor the SIS was adequate to protect the slurry tank
      from the worst credible overpressure scenario. Fundamentally, this is because the
      performance objectives of the venting system and SIS were not clearly defined and
      did not protect against the worst credible overpressure scenario. The lessons
      learned from this accident include: use prior incident data for recognizing
      process hazards; identify targets vulnerable to these hazards; explicitly define
      performance objectives for safeguards to protect against the worst credible
      overpressure scenario. The ultimate lesson learned here is that a liquid trapped
      under pressure above its normal boiling point represents an overpressure hazard.
      To avoid exceeding the design pressure of the receiving vessel, the superheated
      liquid must be discharged slowly so that the vapor production rate caused by
      flashing does not exceed the venting rate of the receiving vessel.

PMID- 15518977
TI  - Consequence modeling using the fire dynamics simulator.
AB  - The use of Computational Fluid Dynamics (CFD) and in particular Large Eddy
      Simulation (LES) codes to model fires provides an efficient tool for the
      prediction of large-scale effects that include plume characteristics, combustion
      product dispersion, and heat effects to adjacent objects. This paper illustrates
      the strengths of the Fire Dynamics Simulator (FDS), an LES code developed by the
      National Institute of Standards and Technology (NIST), through several small and
      large-scale validation runs and process safety applications. The paper presents
      two fire experiments--a small room fire and a large (15 m diameter) pool fire.
      The model results are compared to experimental data and demonstrate good
      agreement between the models and data. The validation work is then extended to
      demonstrate applicability to process safety concerns by detailing a model of a
      tank farm fire and a model of the ignition of a gaseous fuel in a confined space.
      In this simulation, a room was filled with propane, given time to disperse, and
      was then ignited. The model yields accurate results of the dispersion of the gas
      throughout the space. This information can be used to determine flammability and
      explosive limits in a space and can be used in subsequent models to determine the
      pressure and temperature waves that would result from an explosion. The model
      dispersion results were compared to an experiment performed by Factory Mutual.
      Using the above examples, this paper will demonstrate that FDS is ideally suited
      to build realistic models of process geometries in which large scale explosion
      and fire failure risks can be evaluated with several distinct advantages over
      more traditional CFD codes. Namely transient solutions to fire and explosion
      growth can be produced with less sophisticated hardware (lower cost) than needed
      for traditional CFD codes (PC type computer verses UNIX workstation) and can be
      solved for longer time histories (on the order of hundreds of seconds of computed
      time) with minimal computer resources and length of model run. Additionally
      results that are produced can be analyzed, viewed, and tabulated during and
      following a model run within a PC environment. There are some tradeoffs, however,
      as rapid computations in PC's may require a sacrifice in the grid resolution or
      in the sub-grid modeling, depending on the size of the geometry modeled.

PMID- 15518976
TI  - Practicing chemical process safety: a look at the layers of protection.
AB  - This presentation will review a few public perceptions of safety in chemical
      plants and refineries, and will compare these plant workplace risks to some of
      the more traditional occupations. The central theme of this paper is to provide a
      "within-the-fence" view of many of the process safety practices that world class
      plants perform to pro-actively protect people, property, profits as well as the
      environment. It behooves each chemical plant and refinery to have their story on
      an image-rich presentation to stress stewardship and process safety. Such a
      program can assure the company's employees and help convince the community that
      many layers of safety protection within our plants are effective, and protect all
      from harm.

PMID- 15518978
TI  - Human performance breakdowns are rarely accidents: they are usually very poor
      choices with disastrous results.
AB  - When human error is involved in the error chain of accidents in complex systems,
      the causes of the errors are very seldom the result of: a random slip, one
      inadvertent oversight, a single unintended action, one mis-perceived event,
      simple mal-performance of a complex action, or a poor training program for the
      human operators. Invariably, the cause of the break down is in a very poor
      conscious choice by someone from the operator back through system designer, the
      supervision, management and leadership through the entire organization. Usually
      the operator bears the burden of the blame and is either rebuked, retrained or
      replaced. In systems such as commercial aviation, complex manufacturing systems,
      power plants, process control systems, information-processing systems and
      communications networks, the replacement or retraining of individuals or even
      classes of individuals usually does not result in any long-term improvement of
      the safety or effectiveness of the system. What is needed is a system that
      identifies the reasons why the operators made the errors. Further a system is
      needed that can recommend what can be done to improve the future performance
      within the system. The professional performance analysis system (PPAS) has been
      developed and applied to more than 50 major aircraft accidents in the past 30
      years. The PPAS is a direct outgrowth of the human performance analysis system
      developed by Robert Mager over 45 years ago. The PPAS system is applied after a
      complete and unbiased definition and description of the events of the accident or
      incident has been developed by the teams of accident investigation and accident
      reconstruction professionals. The PPAS then uses a systematic protocol and
      algorithm to determine the reasons as to why the humans committed the errors or
      why they performed at subnormal performance levels. This process is based on
      quantitative behavioral science principles and findings that have been
      demonstrated valid for many generations. The PPAS looks at five attributes of
      human performance to identify the factors that can be changed to improve
      performance in the future. The result is a series of objective definitions of
      changes that have been demonstrated to be the attributes that influence human
      performance. The PPAS provides a tool to the analyst, who lacks sophistication or
      experience in quantitative behavioral sciences, to arrive at recommendations that
      are based on validated human performance principles.

PMID- 15518979
TI  - Initial perspectives on process threat management.
AB  - Terrorist and criminal acts are now considered credible risks in the process
      industries. Deliberate attacks on the nation's petroleum refineries and chemical
      plants would pose a significant threat to public welfare, national security, and
      the US economy. To-date, the primary response of government and industry has been
      on improved security to prevent attacks and the associated consequences. While
      prevention is clearly preferred, the potential for successful attacks must be
      addressed. If plant security is breached, the extent of the inflicted damage is
      determined by the available plant safety systems and procedures. We refer to this
      "inside the gate" response as process threat management. The authors have
      initiated a joint industry/academia study to address: the level of safety
      provided by existing plant equipment and safety systems in response to a
      terrorist act, and identification of process (rather than security) needs or
      opportunities to address this new safety concern. This paper describes the
      initial perspectives and issues identified by the team at the beginning of the
      study.

PMID- 15518980
TI  - A new method for defining and managing process alarms and for correcting process
      operation when an alarm occurs.
AB  - A new mathematical treatment of alarms that considers them as multi-variable
      interactions between process variables has provided the first-ever method to
      calculate values for alarm limits. This has resulted in substantial reductions in
      false alarms and hence in alarm annunciation rates in field trials. It has also
      unified alarm management, process control and product quality control into a
      single mathematical framework so that operations improvement and hence economic
      benefits are obtained at the same time as increased process safety. Additionally,
      an algorithm has been developed that advises what changes should be made to
      Manipulable process variables to clear an alarm. The multi-variable Best
      Operating Zone at the heart of the method is derived from existing historical
      data using equation-free methods. It does not require a first-principles process
      model or an expensive series of process identification experiments. Integral with
      the method is a new format Process Operator Display that uses only existing
      variables to fully describe the multi-variable operating space. This combination
      of features makes it an affordable and maintainable solution for small plants and
      single items of equipment as well as for the largest plants. In many cases, it
      also provides the justification for the investments about to be made or already
      made in process historian systems. Field Trials have been and are being conducted
      at IneosChlor and Mallinckrodt Chemicals, both in the UK, of the new geometric
      process control (GPC) method for improving the quality of both process operations
      and product by providing Process Alarms and Alerts of much high quality than ever
      before. The paper describes the methods used, including a simple visual method
      for Alarm Rationalisation that quickly delivers large sets of Consistent Alarm
      Limits, and the extension to full Alert Management with highlights from the Field
      Trials to indicate the overall effectiveness of the method in practice.

PMID- 15518981
TI  - The new risk paradigm for chemical process security and safety.
AB  - The world of safety and security in the chemical process industries has certainly
      changed since 11 September, but the biggest challenges may be yet to come. This
      paper will explain that there is a new risk management paradigm for chemical
      security, discuss the differences in interpreting this risk versus accidental
      risk, and identify the challenges we can anticipate will occur in the future on
      this issue. Companies need to be ready to manage the new chemical security
      responsibilities and to exceed the expectations of the public and regulators.
      This paper will outline the challenge and a suggested course of action.

PMID- 15518982
TI  - Evaluating and assessing process hazard analyses.
AB  - Process hazard analysis (PHA) is widely used across a spectrum of industries and
      facilities, but there are few metrics for the evaluation and assessment of PHAs.
      Most existing protocols address PHA solely in terms of regulatory compliance, but
      do not address the completeness or depth of the assessment, as most PHAs have
      been performed on a "performance basis" under the relevant regulations. It is
      possible to objectively assess PHAs, in order to determine adequacy of completion
      and degree of review, using both audit protocol and scoring approaches. Audit
      protocol approaches offer simplicity and ease of use, and when combined with
      specific scoring for adequacy allow for informed decisions about remedial action
      with respect to the PHA.

PMID- 15518983
TI  - Tracking and predation on earthworms by the invasive terrestrial planarian
      Bipalium adventitium (Tricladida, Platyhelminthes).
AB  - The potential ecological impact of exotic terrestrial planarians will be
      determined in part by their sensory abilities and predatory behavior. It has been
      suggested that these flatworms may only encounter their earthworm prey by chance,
      hence restricting the breadth of species they will feed upon and the number of
      microhabitats in which predator-prey interactions occur. We hypothesized that
      those flatworms that have already successfully invaded North America (genus
      Bipalium) actually detect and follow chemical trails of earthworms and possess
      the behavioral repertoire needed to feed on the prey in a range of microhabitats.
      We examined: (1) the tendency of Bipalium adventitium to follow chemical trails
      left by injured and un-injured earthworms; (2) the behavioral repertoire and
      predatory success of B. adventitium feeding on three earthworm species in
      subterranean tunnels; and (3) the response of flatworms to the reportedly
      defensive secretions of the earthworm Eisenia fetida in tunnels. B. adventitium
      detected and followed trails of earthworm mucus and secretions left by injured
      and un-injured earthworms. Flatworms followed trails on a range of substrates and
      pursued and captured three species of earthworms in subterranean tunnels,
      including individuals many times their mass. Although most behavior exhibited
      during underground attacks was similar to that reported for surface encounters,
      the flatworms also behaved in ways that blocked earthworm escape from tunnels.
      The flatworms were less successful at preying on E. fetida than on Lumbricus
      rubellus and Lumbricus terrestris in underground tunnels and showed some aversion
      to the secretions from E. fetida.

PMID- 15518984
TI  - Behavior strategy learning in rat: effects of lesions of the dorsal striatum or
      dorsal hippocampus.
AB  - Depending on task demands, there is a growing body of evidence suggesting that
      the dorsal striatum plays a critical role in not only learning new response
      strategies but also in the inhibition of pre-existing strategies when a shift in
      strategy is required. The present experiment examined the effects of lesions of
      the dorsal striatum or dorsal hippocampus on acquisition of a response-learning
      rule and a place-learning rule in a Greek Cross version of the Morris water maze.
      Specifically, adult Long-Evans rats were prepared with either sham lesions or
      lesions to one of two subcortical areas of the brain considered necessary for
      processing nondeclarative or declarative memories, the dorsal striatum or the
      hippocampus, respectively. An analysis of the trial 2 performance pooled across
      reversals revealed hippocampus lesions induced accelerated acquisition when a
      response-learning rule was required. A much smaller enhancement effect was
      observed in dorsal striatum-lesioned animals in the place-learning paradigm.
      Dorsal hippocampus- and dorsal striatum-lesioned animals were highly impaired on
      place learning and response learning, respectively. The present results are
      congruent with a growing body of literature suggesting that different anatomical
      substrates are involved in the acquisition and maintenance of different types of
      information, that these processes can occur simultaneously and in parallel, and
      that the dorsal striatum is necessary for the mediation of stimulus-response
      learning, while the hippocampus is necessary to mediate the expression of place
      learning.

PMID- 15518985
TI  - Measuring state changes in human delay discounting: an experiential discounting
      task.
AB  - A new experiential discounting task (EDT) is presented. Unlike existing question
      based measures of delay discounting, which rely on imagined consequences during
      task completion, this EDT requires that participants experience choice
      consequences (i.e. delays and pseudo consumatory responses) during the
      measurement period. As a preliminary examination of this task's sensitivity to
      variability in discounting, 12 participants (six females) completed a timing test
      (production and reproduction), a question-based measure of delay discounting, and
      the EDT during non-sleep-deprived (awake 7 h) and sleep-deprived (awake 21 h)
      conditions. Based on evidence that sleep deprivation increases impulsive
      behavior, it was hypothesized that participants would underrepresent time
      intervals in both production and reproduction procedures and discount
      significantly more with the discounting procedures while sleep deprived.
      Unfortunately, data from the question-based discounting procedure could not be
      reported due to invalid task completion. However, as hypothesized, certain
      production and reproduction intervals were underrepresented on the timing test,
      and discounting was significantly steeper on the EDT when participants were sleep
      deprived. Also, rate of discounting on the EDT was better characterized by a
      hyperbolic function than by exponential function, which is consistent with
      previous delay-discounting research. These preliminary results suggest this EDT
      may be a useful measure for assessing state changes in discounting processes.

PMID- 15518986
TI  - Taste aversion learning induced by delayed swimming activity.
AB  - The experiment reported here demonstrated that forced swimming endows rats with
      aversion to a taste solution consumed 30 min before the swimming. The
      experimental rats were allowed to drink 0.2% sodium saccharin solution, which was
      followed by a 30-min empty interval, and then a 20-min swimming opportunity in
      water. Compared with the control rats, which were returned to their home cages
      after drinking the saccharin, the experimental rats drank a small amount of
      saccharin solution both in the later sessions of one-bottle training and in the
      subsequent two-bottle choice (saccharin versus tap water) testing. The delayed
      swimming procedure was as effective as an immediate swimming procedure, extending
      the generality of the swimming-induced taste aversion, which we recently
      discovered with the immediate swimming procedure.

PMID- 15518987
TI  - Interactions among unit-price, fixed-ratio value, and dosing regimen in
      determining effects of repeated cocaine administration.
AB  - Previous research has shown tolerance to cocaine that was dependent on fixed
      ratio (FR) parameter size in the context of a multiple FR schedule of food
      reinforcement. Completion of the FR requirement in these studies resulted in the
      same magnitude of reinforcement, regardless of ratio size. The cost-to-benefits
      ratio (unit-price) was therefore not equated across the different FR components.
      The current study examined the effects of repeated administration of cocaine to
      pigeons when unit-price under FR schedules was either the same or different.
      Additionally, the role of a chronic variable-dosing versus chronic fixed-dosing
      procedure was examined when unit-price was equated across different ratio values.
      Pigeons were trained to key peck in daily sessions under a three-component
      multiple FR schedule of food presentation, according to which either 10, 30, or
      100 pecks were required for each delivery of food. In Experiment 1, completion of
      the FR 10, FR 30, and FR 100 resulted in 1.5, 4.5, and 15.0 s access to food,
      respectively. That is, the response requirement was correlated with access to
      food time so that unit-price (pecks per second of access to food) was equated
      across components. After assessing acute effects of a range of doses of cocaine,
      drug administration occurred daily before each session, with the dose varying
      from day to day. Tolerance, the magnitude of which was unrelated to the peck
      requirement, developed under the repeated-dosing regimen. In order to assess
      whether having equal unit-price was responsible for producing similar levels of
      tolerance across components, daily drug administration continued in Experiment 2
      using the variable-dose regimen, but the amount of food presented each time was
      fixed at 4.5 s access to food, yielding different unit-prices under the three
      pecking requirements. Subsequently, the conditions of Experiment 1 were
      reinstated, i.e., unit-price was equated. Making unit-price different or the same
      had little influence on effects of cocaine. In Experiment 3, a fixed dose of
      cocaine was administered before each session while programmed unit-price remained
      the same across components. Under these conditions, tolerance became peck
      requirement related. Specifically, tolerance was most prevalent under the smaller
      requirements and less robust or absent when the largest requirement was in
      effect. Differences in unit-price, therefore, were not related to degree of
      tolerance, but work requirement was. Differences in effects of cocaine across
      responses requirements, however, were observed only when each session was
      preceded by the same dose, not when dose varied from session to session.

PMID- 15518988
TI  - Human implicit memory for irrelevant dimension values is similar to rats'
      incidental memory in simultaneous discrimination tasks.
AB  - Participants completed a category-learning task in which they needed to discover
      which of three stimulus dimensions (shape, color or size) was relevant. After
      meeting a learning criterion (nine of 10 consecutive correct responses),
      participants continued making categorization choices and response latencies
      associated with these trials were examined. In both Experiments 1 and 2, people
      responded reliably faster when correct responses matched the previous responses
      with respect to irrelevant dimension values. Thus, they demonstrated a form of
      incidental short-term memory analogous to that we previously reported in studies
      of rats. In Experiment 2, participants' explicit memory for irrelevant dimension
      values was assessed after category learning was complete. The results indicated
      that people were unaware of the irrelevant dimension values encountered on trials
      preceding surprise probe trials. This indicates that memory for the irrelevant
      dimension values was implicit (i.e. unconscious). The findings are discussed with
      respect to both human and non-human studies of hippocampus-independent memory and
      implicit memory.

PMID- 15518989
TI  - Functional equivalence in pigeons involving a four-member class.
AB  - Research suggests that animals are capable of forming functional equivalence
      relations or stimulus classes of the kind usually demonstrated by humans (e.g.,
      the class defined by an object and the word for that object). In pigeons, such
      functional equivalences are typically established using many-to-one matching-to
      sample in which two samples are associated with one comparison stimulus and two
      different samples are associated with the other. Evidence for the establishment
      of functional equivalences between samples associated with the same comparison
      comes from transfer tests. In Experiment 1, we found that pigeons can form a
      single class consisting of four members (many-to-one matching) when the
      alternative class has only one member (one-to-one matching). In Experiment 2, we
      ruled out the possibility that the pigeons acquired the hybrid one-to-one/many-to
      one task by developing a single-code/default coding strategy as earlier research
      suggested that it might. Thus, pigeons can develop a functional class consisting
      of as many as four members, with the alternative class consisting of a single
      member.

PMID- 15518990
TI  - Pigeons shift their preference toward locations of food that take more effort to
      obtain.
AB  - Although animals typically prefer to exert less effort rather than more effort to
      obtain food, the present research shows that requiring greater effort to obtain
      food at a particular location appears to increase the value of that location. In
      Experiment 1, pigeons' initial preference for one feeder was significantly
      reduced by requiring 1 peck to obtain food from that feeder and requiring 30
      pecks to obtain food from the other feeder. In Experiment 2, a similar decrease
      in preference was not found when pigeons received reinforcement from both feeders
      independently of the amount of effort required. These results are consistent with
      the within-trial contrast effect proposed by in which the relative hedonic value
      of a reward depends on the state of the animal immediately prior to the reward.
      The greater the improvement from that prior state the greater the value of the
      reinforcer.

PMID- 15518991
TI  - Operant conditioning in the ant Myrmica sabuleti.
AB  - Operant conditioning could be obtained in the ant Myrmica sabuleti by presenting
      to the workers, during a six-day period, an apparatus containing either sugared
      water or meat as a reward. The conditioning obtained using sugared water as a
      reward was short lasting. A reconditioning was more persistent and lasted four
      hours. The ants' response was very precise, since they exhibited it only in front
      of an apparatus identical to that used during the training phase. Operant
      conditioning obtained using meat as a reward was more pronounced than that
      obtained by using sugared water, probably because meat is more valuable as a
      reward than sugar for the species studied, which is essentially a carnivorous
      one. Such a conditioning was rather persistent. Indeed, a first operant
      conditioning obtained by using meat as a reward could still be detected after
      seven hours, and a reconditioning was still significant after eight hours. One
      day after this eight-hour period without rewarding the ants, the response was
      higher again and a further day later, it was still significant. Since the operant
      conditioning is easy to perform and quantify and since the ants' response is very
      precise, such a conditioning can be used for further studying M. sabuleti
      workers' visual perception.

PMID- 15518992
TI  - Defensive behaviour and biological activities of the abdominal secretion in the
      ant Crematogaster scutellaris (Hymenoptera: Myrmicinae).
AB  - Using bioassays, the defensive behaviour of Crematogaster scutellaris and the
      biological activities of its abdominal secretion were investigated. Beside
      classical aggressive behaviours such as grips, C. scutellaris workers performed
      frequent characteristic gaster flexions during interspecific encounters,
      sometimes tempting to apply their abdominal secretion topically on the enemy. The
      toxicity of the venom of C. scutellaris to other ants greatly differed among the
      species tested, some being killed after the topical application of only three
      droplets, while others were quite resistant to a dose of 90 droplets. All ant
      species tested were strongly and immediately repelled by a contact between their
      antennae or mouthparts with the venom of C. scutellaris. Abdominal secretion was
      never used during intraspecific interference and workers were resistant to a
      topical application of the venom of their own species. Intraspecific repellency
      was significant but moderate compared to interspecific one. Workers of C.
      scutellaris were never seen using their venom during prey capture. In conclusion,
      the main biological activity of the abdominal secretion of C. scutellaris seems
      to be its repellency to other ant species. This is supported by field experiments
      showing that Pheidole pallidula foragers were efficiently repelled at coexploited
      baits, allowing the monopolization of most prey by C. scutellaris.

PMID- 15518993
TI  - The effects of changes in consequences on hens' performance in delayed-matching
      to-sample tasks.
AB  - A delayed-matching-to-sample (DMTS) task was used to investigate remembering with
      domestic hens. In Conditions 1 and 3 of Experiment 1, six hens responded under a
      mixed-delay procedure with delays of 0.25, 2, and 8 s. In Condition 2, the
      reinforcer for correct responding was delayed for 6 s after each correct matching
      response on 2-s delay trials. In Condition 1, discrimination performance
      decreased monotonically over the three delays. With the delay to the reinforcer,
      the decreases were non-monotonic as a result of the considerable drop in the
      accuracy of discrimination on the 2-s delay trials. Performance at the 2-s delay
      did not recover completely in Condition 3. In Conditions 1 and 3 of Experiment 2,
      five hens responded under a mixed-delay procedure with delays of 0, 4, and 16 s.
      In Condition 2 no reinforcers were provided for correct responding on 0- and 16-s
      delay trials. When reinforcers were available on all trials discrimination
      performance decreased monotonically with delay. There were non-monotonic changes
      in discrimination with delay when there was extinction at two delays resulting
      mainly from a large drop in discrimination performance at 0 s. In addition,
      response latencies increased markedly at the two delays associated with
      extinction. Performance recovered completely in Condition 3. The data support the
      ideas that remembering involves a temporal discrimination that the effects of
      delaying reinforcement and removing reinforcement may differ, and that the
      measurement of response latencies may be a useful tool in DMTS procedures.

PMID- 15518994
TI  - Disturbance chemical cues determine changes in spatial occupation by the convict
      cichlid Archocentrus nigrofasciatus.
AB  - I studied the effect of disturbance chemical cues on fish that make trade-offs
      between foraging in an open area and remaining in a safe refuge. I used convict
      cichlids Archocentrus nigrofasciatus that were either visually exposed to a
      predator (n = 8) or exposed to water conditioned by chemical cues from disturbed
      conspecifics (n = 8). Fish visually exposed to a predator decreased their
      ingestion rate and spent more time in the refuge than in the foraging area, while
      fish receiving water from frightened conspecifics did not alter their ingestion
      rate or time spent in the refuge and foraging site, but increased their spatial
      occupation (i.e., motion). These results suggest that convict cichlids recognized
      the predator by visual cues. Moreover, disturbance cues are a form of threatening
      public information that may increase fish spatial occupation due to increased
      exploring behaviour; but is not sufficiently alarming to alter feeding or
      increase refuge use.

PMID- 15518995
TI  - Aromatase inhibition blocks the expression of sexually-motivated cloacal gland
      movements in male quail.
AB  - In Japanese quail (Coturnix japonica), activation of appetitive and consummatory
      aspects of male sexual behavior requires aromatization of testosterone (T) into
      estrogens. Appetitive male sexual behavior (ASB) is usually assessed with the use
      of a learned social proximity procedure. In the present experiment, we
      investigated the role of estrogens in the activation of an another index of ASB,
      the female-induced activation of rhythmic cloacal sphincter movements (RCSMs)
      that are produced in reaction to the visual presentation of a female.
      Consummatory sexual behavior (CSB) was also assessed by the frequency and latency
      of copulatory behaviors. Castrated male quail were treated with Silastic implants
      filled with T in association with chronic injections of the aromatase inhibitor
      Vorozole (R83842; 1mg/kg twice a day; CX + T + VOR group). Control birds were
      implanted with T capsules only (CX + T group). CSB was almost completely blocked
      by injections of the aromatase inhibitor. The RCSM frequency decreased
      progressively in the CX + T + VOR group by comparison with the CX + T group and
      was therefore significantly reduced at the end of the experiment. These results
      demonstrate that the frequency of RCSM, a second measure of ASB is, like the
      social proximity response and CSB, blocked by inhibition of estrogen production.
      It was shown previously that lesions of the preoptic area inhibit both aspects of
      the appetitive sexual behavior (proximity response and RCSM). It is therefore,
      likely that both responses are controlled, like copulation, by aromatase
      containing neurons of the preoptic area.

PMID- 15518996
TI  - The influence of the scout upon the decision-making process of recruited workers
      in three Acromyrmex species (Formicidae: Attini).
AB  - We examined how the information communicated by a scout worker influences the
      plant species transported by recruited workers in Acromyrmex balzani, Acromyrmex
      rugosus, and Acromyrmex crassispinus, three species of leaf-cutting ant that have
      different substrate and habitat preferences. We verified that certain plant
      species were more likely to be transported than others and that recruitment
      occurs. We found that recruited workers were more likely to transport non
      preferred plant species when they were recruited to these by scout workers. The
      results suggest that the scout worker can communicate information about plant
      identity to recruited workers, but that recruited workers integrate the
      information communicated with their own experience during the decision-making
      process.

PMID- 15518997
TI  - Excitatory backward conditioning in an appetitive conditioned reinforcement
      preparation with rats.
AB  - Four experiments were conducted to examine appetitive backward conditioning in a
      conditioned reinforcement preparation. In all experiments, off-line classical
      conditioning was conducted following lever-press training on two levers.
      Presentations of a sucrose solution by a liquid dipper served as an unconditioned
      stimulus (US) and two auditory stimuli served as conditioned stimuli (CSs); one
      was paired with the US in either a forward (Experiment 1a) or a backward
      (Experiments 1b, 2, and 3) relationship, and the other served as a control CS,
      which was not paired with the US. In testing, each lever-press response produced
      a presentation of one of the CSs instead of appetitive reinforcers. The response
      to a lever was facilitated, compared to the response to another lever, when the
      response produced the backward CS presentation as well as when it produced the
      forward CS presentation; that is, the backward CS served as an excitatory
      conditioned reinforcer.

PMID- 15518998
TI  - Transfer between views of conspecific faces at different ages or in different
      orientations by sheep.
AB  - Sheep are able to discriminate photographs of conspecific faces. The present
      study investigates adult ewe's recognition of faces of the same animal between
      different ages or between different orientations. Twelve adult sheep were first
      trained to discriminate between faces of two unfamiliar animals, one of which was
      associated with a food reward. Transfer of discrimination from this pair to the
      same pair but at a different age, or in a different orientation, was then
      evaluated (transfer test), and compared with a new pair of the same condition
      (control test). Learned discrimination of a frontal view of unfamiliar 3-month
      old lambs' faces improved subsequent discrimination of the same pair when they
      were 1-month-old in comparison to discrimination of new 1-month-old faces.
      Moreover, sheep that were trained to discriminate frontal views of unfamiliar
      adult individuals discriminated profile views of the same animals more accurately
      than that of novels. However, learned discrimination of the profile view of
      unfamiliar adult faces had no effect on subsequent discrimination of the frontal
      view of that same pair. These results suggest that to some extent sheep recognise
      faces of unfamiliar animals at different ages and in different orientations.

PMID- 15518999
TI  - Interval timing in Siamese fighting fish (Betta splendens).
AB  - The present study evaluated the temporal performance of Siamese fighting fish
      (Betta splendens) given short-term exposure to four fixed interval (FI) schedules
      of reinforcement, FI 30, 60, 120, and 240 s, during which a reinforcer (mirror
      image) was given for the first response (swimming through a hoop) after the
      interval requirement had elapsed. Response levels were generally low early in an
      interval and increased as the interval elapsed; wait times and break points in an
      interval increased with increases in the FI requirement. The results were similar
      to that obtained with other species and different types of responses and
      reinforcers, and demonstrate that the procedure is a feasible method for studying
      interval timing in fish.

PMID- 15519000
TI  - Lateralisation in birds of prey: adaptive and phylogenetic considerations.
AB  - Lateralisation, the different use of one or other side or appendix of the body,
      is basically determined by brain asymmetry which, in turn, is likely to be due to
      adaptive reasons. Several studies have been carried out on birds in general.
      However, birds of prey in particular, although they are very good candidates,
      have not been investigated from the sensory lateralisation point of view. In
      fact, many species scan for prey while perched and capture terrestrial prey with
      the feet, having at the same time the obvious necessity to keep their balance.
      This paper, therefore, investigates the existence of some sort of lateralisation
      in several species of both Falconiformes and Strigiformes temporarily in
      captivity. Attention is given to: (a) the direction of body rotation when
      perceiving a sound stimulus from behind the body and (b) the use of the feet when
      grasping a terrestrial prey. Lateralisation was found to be clearly present in
      both types of tests, although with some difference in its expression. In fact,
      almost every species tested rotated its body anti-clockwise, i.e. to the left,
      both in the first test and in repeated tests, with no noticeable difference
      between Falconiformes and Strigiformes. Also prey grasping showed a preferential
      use of one foot. Falconiformes preferred clearly to grasp the prey with one foot
      only in both the first test and in subsequent ones. Strigiformes, on the other
      hand, preferred using both feet, although a not insignificant proportion of
      individuals used one foot. Only the little owl seemed to have the tendency to
      prefer to use the right foot only, in a similar manner to Falconiformes. In fact,
      this bird is the most "diurnal" owl species among those tested, suggesting that
      lateralisation in footedness might be affected by adaptive constraints more than
      by phylogenetic similarities. Lateralisation, therefore, seems to be very
      widespread among birds of prey. Preferential use of the right foot also appears
      to be a general habit, and this is probably connected to the use of left
      hemisphere when manipulating food items.

PMID- 15519001
TI  - Introduction of a retention interval in a sustained attention task in rats:
      effects of a visual distracter and increasing the inter-trial interval.
AB  - The impact of manipulating explicit attentional demands on working memory has not
      been well studied in rodents. The present experiment was designed to test the
      effects of incorporating a retention interval in a two-lever sustained attention
      task that requires discrimination of visual signals and non-signals and that has
      previously been shown to yield valid measures of attention in the rat. Upon
      establishing baseline performance, additional manipulations, including
      presentation of a visual distracter and increasing the length and variability of
      the inter-trial interval were conducted. During baseline conditions, accurate
      detection of signals, but not non-signals, decreased as the retention interval
      was increased. Presentation of a flashing houselight throughout the session
      eliminated delay-dependent detection of signals. Increasing the inter-trial
      interval improved detection of signals and decreased detection of non-signals at
      the longest retention interval. Finally, increasing the variability of the inter
      trial interval did not have significant effects on performance above and beyond
      the effects of increasing the inter-trial interval. The present experiment
      demonstrates that manipulation of explicit attentional demands can alter working
      memory performance in the rat. This task may be employed to understand the
      neuropharmacological and neuroanatomical substrates mediating memory while
      attentional load is systematically varied.

PMID- 15519002
TI  - Evidence for an alternation strategy in time-place learning.
AB  - Many different conclusions concerning what type of mechanism rats use to solve a
      daily time-place task have emerged in the literature. The purpose of this study
      was to test three competing explanations of time-place discrimination. Rats (n =
      10) were tested twice daily in a T-maze, separated by approximately 7 h. Food was
      available at one location in the morning and another location in the afternoon.
      After the rats learned to visit each location at the appropriate time, tests were
      omitted to evaluate whether the rats were utilizing time-of-day (i.e., a
      circadian oscillator) or an alternation strategy (i.e., visiting a correct
      location is a cue to visit the next location). Performance on this test was
      significantly lower than chance, ruling out the use of time-of-day. A phase
      advance of the light cycle was conducted to test the alternation strategy and
      timing with respect to the light cycle (i.e., an interval timer). There was no
      difference between probe and baseline performance. These results suggest that the
      rats used an alternation strategy to meet the temporal and spatial contingencies
      in the time-place task.

PMID- 15519003
TI  - Habituation of hissing by Madagascar hissing cockroaches (Gromphadorhina
      portentosa): evidence of discrimination between humans?
AB  - Anecdotal reports suggest that insects can be "tamed" with frequent human
      contact. In the present experiment, repeated handling of Madagascar hissing
      cockroaches by the same person resulted in habituation of the hissing response in
      ten of 12 subjects. These subjects were then handled by a novel person in order
      to determine whether habituation might be specific to a particular human. Four of
      ten "habituated" subjects immediately began to hiss in the presence of the novel
      handler, but again ceased hissing when contact with the familiar person was
      reestablished. Our results suggest that in some cases "taming" may be person
      specific, rather than a generalized response to humans. These preliminary
      findings are the first evidence of discrimination between humans by an insect
      species, although comparable results are well documented in mammals and birds.

PMID- 15519004
TI  - Do high rates of cigarette consumption increase delay discounting? A cross
      sectional comparison of adolescent smokers and young-adult smokers and
      nonsmokers.
AB  - The present report attempts to help clarify the causal or consequent relation
      between frequently reported high rates of delay discounting (DD) associated with
      cigarette-smoking status in adults. Delay-discount functions of adolescent
      smokers and young-adult smokers and nonsmokers from two earlier studies
      [Reynolds, B., Karraker, K., Horn, K., Richards, J.B., 2003. Delay and
      probability discounting as related to different stages of adolescent smoking and
      non-smoking. Behav. Process. 64, 333-344; Reynolds, B., Richards, J.B., Horn, K.,
      Karraker, K., 2004. Delay discounting and probability discounting as related to
      cigarette smoking status in adults. Behav. Process. 65, 35-42] were cross
      sectionally compared. If a high rate of DD is a predisposing factor to future
      smoking status, adolescent and young-adult smokers were expected to have similar
      rates of DD, but both groups were expected to have higher rates of discounting
      than young-adult nonsmokers. Alternatively, if a high rate of cigarette
      consumption over an extended period is related to increases in DD, young-adult
      smokers were expected to discount more than adolescent smokers and young-adult
      nonsmokers. Results supported the hypothesis that a high rate of cigarette
      consumption is related to higher rates of DD, rather than the alternative
      hypothesis that smokers are predisposed with higher rates of DD. Also, after
      combining adolescent and young-adult smokers, self-reported number of cigarettes
      consumed per day was positively correlated with rate of DD; however, reported
      length of smoking history was not correlated with DD. Possible neurological
      mechanisms leading to increased discounting are discussed.

PMID- 15519005
TI  - Contrast nephropathy: review focusing on prevention.
AB  - Contrast nephropathy (CN) accounts for significant morbidity and mortality.
      Patients with pre-existing renal insufficiency, especially those with diabetic
      nephropathy, are at particular risk. Medullary hypoxia due to decreased renal
      blood flow and direct cytotoxicity contribute to the pathogenesis. Contrast
      nephropathy is usually defined as an increase in serum creatinine concentration
      >0.5 mg/dl or 25% above the baseline level within 48 h. Intravenous hydration
      (saline 0.45%, if tolerated 0.9% at a rate of 1 ml/kg/h) 12 h before and after
      contrast exposure and the use of low or iso-osmolality contrast agents are
      advisable. The benefit of low-dose dopamine as well as the selective dopamine-1
      receptor agonist fenoldopam is unproven. Studies on the effectiveness of the
      adenosine antagonist theophylline have led to conflicting results. Because
      theophylline has a narrow therapeutic range and may be associated with adverse
      effects, it is not a prophylactic agent of first choice. The administration of N
      acetylcysteine (NAC) has been evaluated in several trials with inconsistent
      results. Newer data suggest a benefit of high-dose NAC (1,200 mg twice daily) for
      patients receiving high doses (>140 ml) of contrast agent, or those with advanced
      renal insufficiency (creatinine >2.5 mg/dl). Whereas prophylactic hemodialysis
      does not prevent CN, a recent study demonstrated a marked benefit of prophylactic
      hemofiltration.

PMID- 15519006
TI  - Clinical outcomes in managed-care patients with coronary heart disease treated
      aggressively in lipid-lowering disease management clinics: the alliance study.
AB  - OBJECTIVES: This study sought to determine if an aggressive, focused low-density
      lipoprotein cholesterol (LDL-C)-lowering strategy was superior to usual care for
      coronary heart disease (CHD) patients enrolled in health maintenance organization
      or Veterans Administration settings. BACKGROUND: Statin therapy benefits are well
      established. No prospective, randomized studies have tested strategies to
      optimize these benefits in a "real-world" setting. METHODS: A total of 2,442 CHD
      patients with hyperlipidemia were randomized to either an aggressive treatment
      arm using atorvastatin or usual care and followed for 51.5 months on average.
      Atorvastatin-group patients were titrated to LDL-C goals of <80 mg/dl (2.1
      mmol/l) or a maximum atorvastatin dose of 80 mg/day. Usual-care patients received
      any treatment deemed appropriate by their regular physicians. End point
      assessments were complete in 958 atorvastatin-group and 941 usual-care patients.
      Partial assessments occurred in 259 patients in the atorvastatin group and 284
      patients in the usual care group who did not complete four years of study
      participation because of adverse events, withdrawn consent, or follow-up loss.
      The primary efficacy parameter was time to first cardiovascular event. RESULTS: A
      total of 289 (23.7%) patients in the atorvastatin group compared with 333 (27.7%)
      patients in the usual care group experienced a primary outcome (hazard ratio,
      0.83; 95% confidence interval 0.71 to 0.97, p = 0.02). This reduction in
      morbidity was largely due to fewer non-fatal myocardial infarctions (4.3% vs.
      7.7%, p = 0.0002). Levels of LDL-C were reduced more (34.3% vs. 23.3%, p <
      0.0001) and National Cholesterol Education Program goals (LDL-C <100 mg/dl) more
      likely met at end-of-study visits (72.4% vs. 40.0%) in patients receiving
      atorvastatin compared with those receiving usual care. CONCLUSIONS: An
      aggressive, focused statin therapy management strategy outperformed usual care in
      health maintenance organization and Veterans Administration clinic patients with
      CHD.

PMID- 15519007
TI  - Contrast-induced nephropathy in patients undergoing primary angioplasty for acute
      myocardial infarction.
AB  - OBJECTIVES: The aim of this research was to assess the incidence, clinical
      predictors, and outcome of contrast-induced nephropathy (CIN) after primary
      percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI).
      BACKGROUND: Contrast-induced nephropathy is associated with significant morbidity
      and mortality after PCI. Patients undergoing primary PCI may be at higher risk of
      CIN because of hemodynamic instability and unfeasibility of adequate prophylaxis.
      METHODS: In 208 consecutive AMI patients undergoing primary PCI, we measured
      serum creatinine concentration (Cr) at baseline and each day for the following
      three days. Contrast-induced nephropathy was defined as a rise in Cr >0.5 mg/dl.
      RESULTS: Overall, CIN occurred in 40 (19%) patients. Of the 160 patients with
      baseline Cr clearance >/=60 ml/min, only 21 (13%) developed CIN, whereas it
      occurred in 19 (40%) of those with Cr clearance <60 ml/min (p < 0.0001). In
      multivariate analysis, age >75 years (odds ratio [OR] 5.28, 95% confidence
      interval [CI] 1.98 to 14.05; p = 0.0009), anterior infarction (OR 2.17, 95% CI
      0.88 to 5.34; p = 0.09), time-to-reperfusion >6 h (OR 2.51, 95% CI 1.01 to 6.16;
      p = 0.04), contrast agent volume >300 ml (OR 2.80, 95% CI 1.17 to 6.68; p = 0.02)
      and use of intraaortic balloon (OR 15.51, 95% CI 4.65 to 51.64; p < 0.0001) were
      independent correlates of CIN. Patients developing CIN had longer hospital stay
      (13 +/- 7 days vs. 8 +/- 3 days; p < 0.001), more complicated clinical course,
      and significantly higher mortality rate (31% vs. 0.6%; p < 0.001). CONCLUSIONS:
      Contrast-induced nephropathy frequently complicates primary PCI, even in patients
      with normal renal function. It is associated with higher in-hospital complication
      rate and mortality. Thus, preventive strategies are needed, particularly in high
      risk patients.

PMID- 15519008
TI  - Impact of mild or moderate chronic kidney disease on the frequency of restenosis:
      results from the PRESTO trial.
AB  - OBJECTIVES: The goal of this study was to determine if restenosis is increased in
      mild and moderate chronic kidney disease (CKD) patients after percutaneous
      coronary intervention (PCI). BACKGROUND: Mortality is increased in CKD after PCI.
      Restenosis may contribute to increased late mortality. METHODS: We analyzed
      11,187 patients with a creatinine <1.8 mg/dl from the Prevention of REStenosis
      with Tranilast and its Outcomes (PRESTO) trial, grouped by estimated creatinine
      clearance (CrCl) (<60, 60 to 89, >89 ml/min). The Cox proportional hazards models
      investigated the association between CrCl group and death, myocardial infarction,
      and target vessel revascularization (TVR). Generalized estimating equation
      regression models determined the association between CrCl group and lesion
      specific restenosis. RESULTS: At 30 days, there was no difference in myocardial
      infarction, death, or TVR between the CrCl groups. At nine months, mortality was
      higher in the lowest CrCl group (2.2%, 1.2%, 0.8%; p < 0.001), which was no
      longer significant after adjusting for confounding variables. Myocardial
      infarction and TVR were not different between the groups. In patients undergoing
      protocol follow-up angiography, restenosis (>/=50%) was not increased with CKD
      (32%, 32%, 37%; p = 0.02). CONCLUSIONS: Mortality nine months after PCI is mildly
      increased in mild or moderate CKD patients. However, restenosis is not and does
      not account for the increased mortality.

PMID- 15519009
TI  - Economic evaluation of bivalirudin with provisional glycoprotein IIB/IIIA
      inhibition versus heparin with routine glycoprotein IIB/IIIA inhibition for
      percutaneous coronary intervention: results from the REPLACE-2 trial.
AB  - OBJECTIVES: The purpose of this study was to compare the cost of percutaneous
      coronary intervention (PCI) using bivalirudin with provisional platelet
      glycoprotein (GP) IIb/IIIa inhibition with that of heparin + routine GP IIb/IIIa
      inhibition. BACKGROUND: Although GP IIb/IIIa inhibition has been shown to reduce
      ischemic complications in a broad range of patients undergoing PCI, many patients
      currently do not receive such therapy because of concerns about bleeding
      complications or cost. Recently, bivalirudin with provisional GP IIb/IIIa
      inhibition has been validated as an alternative to heparin + routine GP IIb/IIIa
      inhibition for patients undergoing PCI. However, the cost-effectiveness of this
      novel strategy is unknown. METHODS: In the Randomized Evaluation in PCI Linking
      Angiomax to Reduced Clinical Events (REPLACE)-2 trial, 4,651 U.S. patients
      undergoing non-emergent PCI were randomized to receive bivalirudin with
      provisional GP IIb/IIIa (n = 2,319) versus heparin + routine GP IIb/IIIa (n =
      2,332). Resource utilization data were collected prospectively through 30-day
      follow-up on all U.S. patients. Medical care costs were estimated using standard
      methods including bottom-up accounting (for procedural costs), the Medicare fee
      schedule (for physician services), hospital billing data (for 2,821 of 4,862
      admissions), and regression-based approaches for the remaining hospitalizations.
      RESULTS: Among the bivalirudin group, 7.7% required provisional GP IIb/IIIa.
      Thirty-day ischemic outcomes including death or myocardial infarction were
      similar for the bivalirudin and GP IIb/IIIa groups, but bivalirudin resulted in
      lower rates of major bleeding (2.8% vs. 4.5%, p = 0.002) and minor bleeding
      (15.1% vs. 28.1%, p < 0.001). Compared with routine GP IIb/IIIa, in-hospital and
      30-day costs were reduced by $405 (95% confidence interval [CI] $37 to $773) and
      $374 (95% CI $61 to $688) per patient with bivalirudin (p < 0.001 for both).
      Regression modeling demonstrated that, in addition to the costs of the
      anticoagulants themselves, hospital savings were due primarily to reductions in
      major bleeding (cost savings = $107/patient), minor bleeding ($52/patient), and
      thrombocytopenia ($47/patient). CONCLUSIONS: Compared with heparin + routine GP
      IIb/IIIa inhibition, bivalirudin + provisional GP IIb/IIIa inhibition resulted in
      similar acute ischemic events and cost savings of $375 to $400/patient depending
      on the analytic perspective.

PMID- 15519010
TI  - Cost-effectiveness of distal embolic protection for patients undergoing
      percutaneous intervention of saphenous vein bypass grafts: results from the SAFER
      trial.
AB  - OBJECTIVES: The goal of this research was to determine the incremental cost and
      cost-effectiveness of embolic protection in patients undergoing percutaneous
      revascularization (PCI) of diseased saphenous vein bypass grafts (SVGs).
      BACKGROUND: Distal protection using the GuardWire balloon occlusion device has
      been shown to reduce major ischemic complications in patients undergoing SVG PCI,
      but the cost-effectiveness of this approach is unknown. METHODS: We prospectively
      measured medical resource utilization and cost for 801 patients undergoing SVG
      intervention who were randomized to distal protection using the GuardWire (n =
      406) or conventional treatment (n = 395) in the Saphenous Vein Graft Angioplasty
      Free of Emboli Randomized (SAFER) trial. Long-term survival and cost
      effectiveness were projected based on observed 30-day outcomes and a validated
      survival model for postcoronary artery bypass graft patients. RESULTS: Compared
      with conventional treatment, distal protection increased initial procedural costs
      by approximately $1,600 ($6,326 vs. $4,779, p < 0.001). However, by reducing
      ischemic complications, distal protection reduced mean length of stay by 0.4 days
      and other hospital costs by nearly $1,000 ($6,846 vs. $7,811, p = 0.018). As a
      result, overall initial hospital costs were only $582 per patient higher with
      distal protection. Based on the observed 30-day cost and outcome differences in
      the trial, the incremental cost-effectiveness ratio for distal protection was
      $3,718 per year of life saved and remained <$40,000 per year of life saved in
      97.3% of bootstrap simulations (95% confidence interval, $0 to $43,079).
      CONCLUSIONS: For patients undergoing PCI of diseased SVGs, distal protection
      using the GuardWire system is an attractive use of limited health care resources.

PMID- 15519011
TI  - Economic impact of new interventional therapies: are we asking the right
      questions?

PMID- 15519012
TI  - Association among plasma levels of monocyte chemoattractant protein-1,
      traditional cardiovascular risk factors, and subclinical atherosclerosis.
AB  - OBJECTIVES: We sought to evaluate the association between plasma levels of
      monocyte chemoattractant protein (MCP)-1 and the risk for subclinical
      atherosclerosis. BACKGROUND: Monocyte chemoattractant protein is a chemokine that
      recruits monocytes into the developing atheroma and may contribute to
      atherosclerotic disease development and progression. Plasma levels of MCP-1 are
      independently associated with prognosis in patients with acute coronary
      syndromes, but few population-based data are available from subjects in earlier
      stages of atherosclerosis. METHODS: In the Dallas Heart Study, a population-based
      probability sample of adults in Dallas County </=65 years old, plasma levels of
      MCP-1 were measured in 3,499 subjects and correlated with traditional
      cardiovascular risk factors, high-sensitivity C-reactive protein (hs-CRP), and
      coronary artery calcium (CAC) measured by electron beam computed tomography.
      RESULTS: Higher MCP-1 levels were associated with older age, white race, family
      history of premature coronary disease, smoking, hypertension, diabetes,
      hypercholesterolemia, and higher levels of hs-CRP (p < 0.01 for each). Similar
      associations were observed between MCP-1 and risk factors in the subgroup of
      participants without detectable CAC. Compared with the subjects in the lowest
      quartile of MCP-1, the odds of prevalent CAC (CAC score >/=10) for subjects in
      the second, third, and fourth quartiles were 1.30 (95% confidence interval [CI]
      0.99 to 1.73), 1.60 (95% CI 1.22 to 2.11), and 2.02 (95% CI 1.54 to 2.63),
      respectively. The association between MCP-1 and CAC remained significant when
      adjusted for traditional cardiovascular risk factors, but not when further
      adjusted for age. CONCLUSIONS: In a large population-based sample, plasma levels
      of MCP-1 were associated with traditional risk factors for atherosclerosis,
      supporting the hypothesis that MCP-1 may mediate some of the atherogenic effects
      of these risk factors. These findings support the potential role of MCP-1 as a
      biomarker target for drug development.

PMID- 15519013
TI  - Plasma leptin and prognosis in patients with established coronary
      atherosclerosis.
AB  - OBJECTIVES: This study was designed to evaluate the relationship between plasma
      leptin and prognosis in patients with angiographically confirmed coronary
      atherosclerosis. BACKGROUND: Experimental studies suggest that leptin, an adipose
      tissue-derived hormone, exerts important cardiovascular effects. METHODS: Study
      subjects were recruited prospectively from a cohort of patients undergoing
      clinically indicated coronary angiography (n = 382). The median duration of
      follow-up was four years. Follow-up information was available for 361 patients.
      RESULTS: The combined end point of cardiac death, myocardial infarction (MI),
      cerebrovascular accident, or re-vascularization occurred in 44 subjects. In the
      simple Cox model, leptin had a significant (p < 0.001) non-linear/cubic
      univariate relationship with the combined end point. Other variables associated
      with prognosis in the univariate analysis were body mass index (BMI), prior MI,
      insulin resistance, C-reactive protein (CRP), fibrinogen, and number of coronary
      vessels with >50% stenosis. A positive relationship between leptin and prognosis
      was also seen when leptin levels were split by quintiles, with a hazard ratio of
      6.46 for the highest quintile. The only two variables significantly associated
      with the combined end point in the multivariate Cox model were leptin (p = 0.004)
      and number of coronary vessels with >50% stenosis (p < 0.001). A similar
      relationship between leptin and prognosis was observed when leptin was adjusted
      for BMI. CONCLUSIONS: In patients with angiographically confirmed coronary
      atherosclerosis, leptin is a novel predictor of future cardiovascular events
      independent of other risk factors, including lipid status and CRP.

PMID- 15519014
TI  - Impact of initiating carvedilol before angiotensin-converting enzyme inhibitor
      therapy on cardiac function in newly diagnosed heart failure.
AB  - OBJECTIVES: The purpose of this research was to evaluate the therapeutic value of
      initiating a beta-blocker before an angiotensin-converting enzyme inhibitor
      (ACEI) in the treatment of heart failure. BACKGROUND: Although ACEI and
      carvedilol produce benefits in heart failure, whether the order of initiation of
      therapy determines the impact on left ventricular (LV) function and New York
      Heart Association functional class (NYHA FC) has not been determined. METHODS: A
      single-center, prospective, randomized, open-label study was performed. We
      evaluated whether initiation of therapy with carvedilol either before (n = 38) or
      after (n = 40) perindopril therapy in newly diagnosed patients in NYHA FC II to
      III heart failure with idiopathic dilated cardiomyopathy, with the addition of
      the alternative agent after six months, determined subsequent changes in NYHA FC
      and LV function (echocardiography and radionuclide ventriculography). Study drugs
      were titrated to maximum tolerable doses. RESULTS: There were no differences in
      baseline characteristics between the study groups. After 12 months 11 patients
      died (6 in the group where the ACEI was initiated). At 12 months the group
      receiving carvedilol as initial therapy achieved a higher tolerable dose of
      carvedilol (43 +/- 17 mg vs. 33 +/- 18 mg, p = 0.03); a lower dose of furosemide
      (p < 0.05); and better improvements in symptoms (NYHA FC, p < 0.002), LV ejection
      fraction (radionuclide: 15 +/- 16% vs. 6 +/- 13%, p < 0.05; echocardiographic, p
      < 0.01), and plasma N-terminal pro-brain natriuretic peptide concentrations (p <
      0.02). CONCLUSIONS: As opposed to the conventional sequence of drug use in the
      treatment of heart failure, initiation of therapy with carvedilol before an ACEI
      results in higher tolerable doses of carvedilol and better improvements in FC and
      LV function.

PMID- 15519015
TI  - Dismantling mandates in the treatment of heart failure.

PMID- 15519016
TI  - Left ventricular dyssynchrony predicts response and prognosis after cardiac
      resynchronization therapy.
AB  - OBJECTIVES: This study was designed to predict the response and prognosis after
      cardiac resynchronization therapy (CRT) in patients with end-stage heart failure
      (HF). BACKGROUND: Cardiac resynchronization therapy improves HF symptoms,
      exercise capacity, and left ventricular (LV) function. Because not all patients
      respond, preimplantation identification of responders is needed. In the present
      study, response to CRT was predicted by the presence of LV dyssynchrony assessed
      by tissue Doppler imaging. Moreover, the prognostic value of LV dyssynchrony in
      patients undergoing CRT was assessed. METHODS: Eighty-five patients with end
      stage HF, QRS duration >120 ms, and left bundle-branch block were evaluated by
      tissue Doppler imaging before CRT. At baseline and six months follow-up, New York
      Heart Association functional class, quality of life and 6-min walking distance,
      LV volumes, and LV ejection fraction were determined. Events (death,
      hospitalization for decompensated HF) were obtained during one-year follow-up.
      RESULTS: Responders (74%) and nonresponders (26%) had comparable baseline
      characteristics, except for a larger dyssynchrony in responders (87 +/- 49 ms vs.
      35 +/- 20 ms, p < 0.01). Receiver-operator characteristic curve analysis
      demonstrated that an optimal cutoff value of 65 ms for LV dyssynchrony yielded a
      sensitivity and specificity of 80% to predict clinical improvement and of 92% to
      predict LV reverse remodeling. Patients with dyssynchrony >/=65 ms had an
      excellent prognosis (6% event rate) after CRT as compared with a 50% event rate
      in patients with dyssynchrony <65 ms (p < 0.001). CONCLUSIONS: Patients with LV
      dyssynchrony >/=65 ms respond to CRT and have an excellent prognosis after CRT.

PMID- 15519017
TI  - A hard look at angiotensin receptor blockers in heart failure.
AB  - Multiple trials over the past several years have examined indications for
      angiotensin receptor blockers (ARBs) in the treatment of left ventricular
      dysfunction, both acutely after myocardial infarction and in chronic heart
      failure. Yet despite these data, there is still confusion regarding the efficacy
      of ARBs as monotherapy in these patient populations, as well as the specific
      indications for combination ARB/angiotensin-converting enzyme (ACE) inhibitor
      therapy. We examine the key differences among the trials-including the ACE
      inhibitor dose, the ARB and its dose, blood pressure reduction, and patient
      populations-to present our perspective on ARB use, alone or in combination with
      ACE inhibitors, in patients with chronic heart failure and post-myocardial
      infarction left ventricular dysfunction. We conclude that ACE inhibitors remain
      the first-line therapy for left ventricular dysfunction. Angiotensin receptor
      blockers should be reserved for monotherapy in ACE intolerant patients and for
      combination therapy in symptomatic class II/III patients with chronic heart
      failure.

PMID- 15519018
TI  - Relation of weights of operatively excised stenotic aortic valves to preoperative
      transvalvular peak systolic pressure gradients and to calculated aortic valve
      areas.
AB  - OBJECTIVES: The purpose of this study was to correlate the weights of operatively
      excised stenotic aortic valves to preoperative transvalvular peak systolic
      gradients and to calculated aortic valve areas. BACKGROUND: No previous
      publication has correlated the weights of stenotic aortic valves to the
      transvalvular gradients or to the calculated aortic valve areas. METHODS: We
      weighed operatively excised stenotic aortic valves in 324 adults who had
      undergone preoperative left-sided cardiac catheterization. RESULTS: As the
      weights of the operatively excised stenotic aortic valves increased (from <1 g to
      >6 g), the average transvalvular peak systolic pressure gradients progressively
      increased. For any valve weight, in general, the women had higher average
      transvalvular gradients (p </= 0.005) and lower average valve areas (p </= 0.008)
      than did the men. Correlation between aortic valve weight and transvalvular
      gradient improved further when gender was taken into account. CONCLUSIONS:
      Preoperative transvalvular peak systolic pressure gradients across stenotic
      aortic valves correlate better with the weights of the operatively excised valves
      than do the calculated valve areas.

PMID- 15519019
TI  - Low flow-low gradient aortic stenosis: the pathologist weighs in.

PMID- 15519020
TI  - Induction of local angiotensin II-producing systems in stenotic aortic valves.
AB  - OBJECTIVES: The purpose of this study was to investigate the expression of
      angiotensin II (Ang II)-producing enzyme systems in normal and stenotic aortic
      valves. BACKGROUND: Chronic inflammation and fibrosis are involved in the
      pathogenesis of aortic stenosis (AS), but the detailed molecular mechanisms of
      this atherosclerosis-like process remain obscure. Angiotensin II, a powerful
      mediator of inflammation and fibrosis, may participate in AS progression.
      METHODS: Stenotic aortic valves (n = 86) were obtained from patients undergoing
      valve replacement surgery, and control valves (n = 11) were obtained from
      patients undergoing cardiac transplantation. Angiotensin-converting enzyme (ACE)
      and mast cell (MC)-derived chymase were quantified by reverse-transcription
      polymerase chain reaction, autoradiography, and immunostaining. The MCs,
      macrophages, and T lymphocytes were detected by immunohistochemistry, and
      angiotensin II type 1 receptor (AT-1R) by autoradiography. RESULTS: Compared with
      control valves, stenotic aortic valves showed a significant increase in both
      messenger ribonucleic acid (mRNA) (p = 0.001) and protein (p < 0.001) expression
      of ACE, which colocalized with macrophages. Similarly, the expression of AT-1R
      protein and chymase mRNA and protein was upregulated (p < 0.001), and the number
      of MCs was six-fold higher in stenotic than in normal valves. The MCs were
      associated with the calcified areas, and-in contrast to control valves-showed an
      increased degree of degranulation, a prerequisite for chymase secretion and
      action. CONCLUSIONS: Angiotensin-converting enzyme and chymase, two Ang II
      forming enzymes, are locally expressed in aortic valves, and owing to
      infiltration of macrophages and MCs, are further upregulated in stenotic valves.
      These novel findings, implicating chronic inflammation and an increased
      expression of local Ang II-forming systems, suggest that therapeutic
      interventions aiming at inhibiting these processes may slow AS progression.

PMID- 15519021
TI  - Diagnostic performance of coronary magnetic resonance angiography as compared
      against conventional X-ray angiography: a meta-analysis.
AB  - OBJECTIVES: This study was designed to define the current role of coronary
      magnetic resonance angiography (CMRA) for the diagnosis of coronary artery
      disease (CAD). BACKGROUND: Coronary magnetic resonance angiography has been
      proposed as a promising noninvasive method for diagnosis of CAD, but individual
      studies evaluating its clinical value have been of limited sample size. METHODS:
      We identified all studies (MEDLINE and EMBASE) that evaluated CAD by both CMRA
      and conventional angiography in >/=10 subjects during the period 1991 to January
      2004. We recorded true and false positive and true and false negative CMRA
      assessments for detection of CAD using X-ray angiography as the reference
      standard. Analysis was done at segment, vessel, and subject level. RESULTS: We
      analyzed 39 studies (41 separate comparisons). Across 25 studies (27 comparisons)
      with data on 4,620 segments (993 subjects), sensitivity and specificity for
      detection of CAD were 73% and 86%, respectively. Vessel-level analyses (16
      studies, 2,041 vessels) showed sensitivity 75% and specificity 85%. Subject-level
      analyses (13 studies, 607 subjects) showed sensitivity 88% and specificity 56%.
      At the segment level, sensitivity was 69% to 79% for all but the left circumflex
      (61%) coronary artery; specificity was 82% to 91%. There was considerable between
      study heterogeneity, but weighted summary receiver-operating characteristic
      curves agreed with these estimates. There were no major differences between
      subgroups based on technical or population characteristics, year of publication,
      reported blinding, or sample size. CONCLUSIONS: In evaluable segments of the
      native coronary arteries, CMRA has moderately high sensitivity for detecting
      significant proximal stenoses and may have value for exclusion of significant
      multivessel CAD in selected subjects considered for diagnostic catheterization.

PMID- 15519022
TI  - Functional significance of stenoses in coronary artery bypass grafts. Evaluation
      by single-photon emission computed tomography perfusion imaging, cardiovascular
      magnetic resonance, and angiography.
AB  - OBJECTIVES: This study was designed to perform a head-to-head comparison between
      single-photon emission computed tomography (SPECT) and cardiovascular magnetic
      resonance (CMR) to evaluate hemodynamic significance of angiographic findings in
      bypass grafts. BACKGROUND: The hemodynamic significance of a bypass graft
      stenosis may not always accurately be determined from the coronary angiogram. A
      variety of diagnostic tests (invasive or noninvasive) can further characterize
      the hemodynamic consequence of a lesion. METHODS: Fifty-seven arterial and vein
      grafts in 25 patients were evaluated by angiography, SPECT perfusion imaging, and
      coronary flow velocity reserve determination by CMR. Based on angiography and
      SPECT, four different groups could be identified: 1) no significant stenosis
      (<50%), normal perfusion; 2) significant stenosis (>/=50%), abnormal perfusion;
      3) significant stenosis, normal perfusion (no hemodynamic significance); and 4)
      no significant stenosis, abnormal perfusion (suggesting microvascular disease).
      RESULTS: A complete evaluation was obtained in 46 grafts. Single-photon emission
      computed tomography and CMR provided similar information in 37 of 46 grafts
      (80%), illustrating good agreement (kappa = 0.61, p < 0.001). Eight grafts
      perfused a territory with scar tissue. When agreement between SPECT and CMR was
      restricted to grafts without scar tissue, it improved to 84% (kappa = 0.68).
      Integration of angiography with SPECT categorized 14 lesions in group 1, 23 in
      group 2, 6 in group 3, and 3 in group 4. Single-photon emission computed
      tomography and CMR agreement per group was 86%, 78%, 100%, and 33%, respectively.
      CONCLUSIONS: Head-to-head comparison showed good agreement between SPECT and CMR
      for functional evaluation of bypass grafts. Cardiovascular magnetic resonance may
      offer an alternative method to SPECT for functional characterization of
      angiographic lesions.

PMID- 15519024
TI  - The heart does not have Alzheimer's disease: electrical and mechanical cardiac
      memory after ventricular pacing.

PMID- 15519023
TI  - Left ventricular function during and after right ventricular pacing.
AB  - OBJECTIVES: The aim of this research was to evaluate right ventricular pacing
      effects on left ventricular function. BACKGROUND: Right ventricular pacing alters
      the ventricular activation sequence and reduces left ventricular ejection
      fraction (EF). It is unclear whether the observed reduction in EF can be
      completely attributed to the alteration in activation sequence. METHODS: Twelve
      subjects (eight women), mean age 68 +/- 12 years, with transvenous dual-chamber
      pacemakers, normal left ventricular function, and intact atrioventricular (AV)
      conduction were studied with serial-gated blood pool studies. Left ventricular EF
      was measured at a fixed rate after at least 1 week of atrial pacing only
      (baseline), during short-term (2 h) and mid-term (1 week) AV sequential pacing
      with a short AV delay, and after short- and mid-term AV pacing. RESULTS: Baseline
      EF was 66.5 +/- 4.5%. Short-term AV pacing resulted in a decrease in EF to 60.3
      +/- 5.2% (p < 0.0002). After one week of AV pacing, there was a further decline
      in EF to 52.9 +/- 8.3% (p < 0.0001). After cessation of mid-term pacing, EF was
      57.3 +/- 5.9% (p < 0.0001 vs. baseline). A total of 2, 5, 8, and 24 h later, EF
      remained depressed (59% to 60%, p < 0.007). At 32 h, EF was 62.9 +/- 7.6% (p <
      0.11 compared with baseline). CONCLUSIONS: The abnormal activation sequence
      resulting from right ventricular pacing accounts for only part of the reduction
      in EF as mid-term pacing is associated with a lower EF than short-term pacing,
      and EF remains depressed after cessation of AV pacing. Changes in ventricular
      function induced by right ventricular pacing may account for some of its
      associated adverse effects.

PMID- 15519025
TI  - Beat-to-beat analysis of pressure wave morphology for pre-symptomatic detection
      of orthostatic intolerance during head-up tilt.
AB  - OBJECTIVES: The aim of this study was to noninvasively define the hemodynamic
      profile characterizing the early response to tilting. BACKGROUND: The mechanisms
      causing orthostatic intolerance have not been fully elucidated. Usually, patients
      undergoing tilt test are studied in a time-consuming way. Moreover, the test can
      cause discomfort to the patient and even be potentially hazardous. METHODS:
      Nineteen orthostatic intolerant patients (OIP), compared with 22 healthy subjects
      (HS), performed head-up tilt test while their arterial pressure waveform was
      noninvasively recorded. We elaborated data using the Pressure Recording
      Analytical Method to obtain hemodynamic parameters, then analyzing the variables
      by discriminant analysis. RESULTS: Compared with HS, OIP showed lower stroke
      volume index (SVI) values even in baseline conditions associated with higher
      values of systemic vascular resistance (SVR) and heart rate (HR). From the third
      minute of the tilted position and until symptoms appeared, patients exhibited
      lower values of blood pressure (BP) and SVI and higher HR values but no
      difference in SVR. At termination, patients showed a further significant
      reduction in BP and SVI and a persistent increase in HR. CONCLUSIONS: This
      investigation underlines: 1) the possibility of beat-to-beat monitoring of
      hemodynamic changes during tilting; 2) the cardiovascular profile of OIP at rest,
      characterized by lower SVI and higher SVR and HR; 3) the maladaptive response to
      postural challenge of OIP mainly identifiable in impaired vascular regulation;
      and 4) the possibility of detecting parameters that enable prompt identification
      of the positive response to tiltingin these patients, thus guiding the duration
      of the test.

PMID- 15519026
TI  - An algorithm to predict implantable cardioverter-defibrillator lead failure.
AB  - OBJECTIVES: The goal of this analysis was to test an algorithm that identifies
      implantable cardioverter-defibrillator (ICD) lead problems before clinical
      failure and/or inappropriate therapy. BACKGROUND: The ICD lead failures typically
      present as inappropriate shock therapy. Identifying lead failures before their
      clinical presentation may prevent patient discomfort, improve device longevity,
      and avoid device-induced proarrhythmia. METHODS: We tested an algorithm that uses
      two measures of oversensing and one measure of abnormal impedance to detect a
      lead failure. The oversensing measures consisted of a counter for RR intervals
      <140 ms and nonsustained ventricular tachycardia episodes with mean RR interval
      <200 ms. The impedance measure tracked lead impedances every day and each week.
      Abnormal impedance was defined as a decrease in impedances or an outlier value
      compared with baseline. Lead failures were identified when both oversensing
      measures were met or abnormal impedance and one oversensing measure occurred. The
      stored data from 696 patients with an ICD were analyzed to determine the
      sensitivity and specificity of the algorithm to detect lead failures. RESULTS:
      Twenty-nine patients demonstrated clinical lead failures with an average of 6 +/-
      9 inappropriate shocks per patient. The two oversensing measures used in the
      algorithm predicted 72% (21 of 29) of the lead failures. Fulfilling at least two
      of the three impedance and oversensing measures, the sensitivity of our algorithm
      was 83% (24 of 29) with a 100% (667 of 667) specificity. CONCLUSION: Oversensing
      combined with abnormal impedance trends may be used to identify ICD lead failures
      with high sensitivity and very high specificity.

PMID- 15519027
TI  - Myosin binding protein C mutations and compound heterozygosity in hypertrophic
      cardiomyopathy.
AB  - OBJECTIVES: We sought to determine the frequency and phenotype of mutations in
      myosin binding protein C (MYBPC3) in a large outpatient cohort of patients with
      hypertrophic cardiomyopathy (HCM) seen at our tertiary referral center.
      BACKGROUND: Mutations in MYBPC3 are one of the most frequent genetic causes of
      HCM and have been associated with variable onset of disease and prognosis.
      However, the frequency of mutations and associated clinical presentation have not
      been established in a large, unrelated cohort of patients. METHODS: Using
      deoxyribonucleic acid from 389 unrelated patients with HCM, each protein coding
      exon of MYBPC3 was analyzed for mutations by polymerase chain reaction,
      denaturing high-performance liquid chromatography, and direct deoxyribonucleic
      acid sequencing. Clinical data were extracted from patient records blinded to
      patient genotype. RESULTS: Of 389 patients with HCM, 71 (18%) had mutations in
      MYBPC3. In all, 46 mutations were identified, 33 of which were novel (72%).
      Patients with MYBPC3 mutations did not differ significantly from patients with
      thick filament-HCM, thin filament-HCM, or genotype-negative HCM with respect to
      age at diagnosis, degree of hypertrophy, incidence of myectomy, or family history
      of HCM or sudden death. Patients with multiple mutations (n = 10, 2.6%) had the
      most severe disease presentation. CONCLUSIONS: This study defines the frequency
      and associated phenotype for MYBPC3 and/or multiple mutations in HCM in the
      largest cohort to date. In this cohort, unrelated patients with MYBPC3-HCM
      virtually mimicked the phenotype of those with mutations in the beta-myosin heavy
      chain. Patients with multiple mutations had the most severe phenotype.

PMID- 15519028
TI  - Smoking and caffeine have a synergistic detrimental effect on aortic stiffness
      and wave reflections.
AB  - OBJECTIVES: We investigated the acute and chronic combined effect of cigarette
      smoking and caffeine intake on aortic stiffness and wave reflections. BACKGROUND:
      We have shown that smoking and caffeine separately increase arterial stiffness.
      Aortic stiffness and wave reflections are important determinants of the efficient
      performance of the cardiovascular system and prognosticators of cardiovascular
      risk. METHODS: The acute effects of smoking (one cigarette), caffeine (200 mg,
      equivalent to 2 cups of coffee), and smoking plus caffeine were studied in 24
      healthy subjects according to a randomized, placebo- and sham procedure
      controlled crossover design. The chronic effect of smoking and caffeine was
      studied in a population study that enrolled 160 healthy subjects. RESULTS: Acute
      study: there was a significant interaction between caffeine and smoking with
      regard to pulse-wave velocity (p < 0.01) and augmentation index (p < 0.05). When
      smoking followed caffeine intake, pulse-wave velocity and augmentation index
      increased further by 0.52 m/s and 13.4%, respectively, reaching a total of 0.85
      m/s and 17.4%, 0.17 m/s and 9.2% in excess of the mere sum of caffeine effect
      (0.33 m/s and 4%) alone and smoking effect alone (0.35 m/s and 4.2%). Population
      study: there was a significant interaction of chronic coffee consumption and
      smoking regarding pulse-wave velocity (p < 0.05) and augmentation index (p =
      0.001). CONCLUSIONS: The present study shows, for the first time, that when
      smoking and caffeine intake are combined, they interact and exert a synergistic,
      unfavorable effect on aortic stiffness and wave reflections on both an acute and
      chronic basis.

PMID- 15519029
TI  - Moderate and chronic hemodynamic overload of sheep atria induces reversible
      cellular electrophysiologic abnormalities and atrial vulnerability.
AB  - OBJECTIVES: The aim of this study was to evaluate the myocardial consequences of
      a chronic volume overload of the left atrium (LA). BACKGROUND: Atrial dilation is
      a major risk factor for atrial fibrillation (AF), but the underlying mechanisms
      are poorly understood. METHODS: A left-right aorto-pulmonary artery shunt (APS)
      was created in sheep. The cardiopathy was characterized by echocardiography,
      electrophysiologic testing, and histologic analysis. Cellular action potential
      (AP) and calcium current (I(Ca)) were recorded by means of microelectrode and
      patch clamp techniques. RESULTS: Three to four months after surgery, all animals
      in the APS state had a dilated LA (146.2 +/- 35.4 cm(2)/m(2) vs. 91.7 +/- 10.4
      cm(2)/m(2) in the control state; p = 0.0024) but remained in sinus rhythm.
      Repetitive atrial firing was triggered by a single extra beat in five of six
      animals in the APS state and in two of six animals in the control state.
      Moreover, in two animals in the APS state, a single extra beat triggered
      sustained AF. Myocytes were enlarged and 39.8% showed some degree of myolysis. In
      animals in the APS state, the AP had no plateau phase or small amplitude and
      numerous myocytes were unexcitable. The I(Ca) density was 45.2% lower in APS
      animals than in control animals. Beta-adrenergic stimulation normalized I(Ca) and
      restored the plateau phase of the AP. After shunt suppression, the
      electrophysiologic properties of the atria returned to normal. CONCLUSIONS: The
      APS induced moderate, isolated LA dilation, which was sufficient to cause major
      changes in cellular electrophysiologic properties and to render the atria
      vulnerable to fibrillation. These effects were reversed by shunt suppression.

PMID- 15519030
TI  - Cardiac resynchronization therapy: a novel adjunct to the treatment and
      prevention of systemic right ventricular failure.
AB  - OBJECTIVES: This study aimed to evaluate the technical feasibility and
      hemodynamic benefit of cardiac resynchronization therapy (CRT) in patients with
      systemic right ventricle (RV). BACKGROUND: Patients with a systemic RV are at
      high risk of developing heart failure. Cardiac resynchronization therapy may
      improve RV function in those with electromechanical dyssynchrony. METHODS: Eight
      patients (age 6.9 to 29.2 years) with a systemic RV and right bundle-branch block
      (n = 2) or pacing from the left ventricle (LV) (n = 6) with a QRS interval of 161
      +/- 21 ms underwent CRT (associated with cardiac surgery aimed at decrease in
      tricuspid regurgitation in 3 of 8 patients) and were followed-up for a median of
      17.4 months. RESULTS: Change from baseline rhythm to CRT was accompanied by a
      decrease in QRS interval (-28.0%, p = 0.002) and interventricular mechanical
      delay (-16.7%, p = 0.047) and immediate improvement in the RV filling time
      (+10.9%, p = 0.002), Tei index (-7.7%, p = 0.008), estimated RV maximum
      +dP/dt(+45.9%, p = 0.007), aortic velocity-time integral (+7.0%, p = 0.028), and
      RV ejection fraction by radionuclide ventriculography (+9.6%, p = 0.04). The RV
      fractional area of change increased from a median of 18.1% before
      resynchronization to 29.5% at last follow-up (p = 0.008) without a significant
      change in the end-diastolic area (+4.0%, p = NS). CONCLUSIONS: The CRT yielded
      improvement in systemic RV function in patients with spontaneous or LV pacing
      induced electromechanical dyssynchrony and seems to be a promising adjunct to the
      treatment and prevention of systemic RV failure.

PMID- 15519031
TI  - N-terminal pro-brain natriuretic peptide in relation to inflammation, myocardial
      necrosis, and the effect of an invasive strategy in unstable coronary artery
      disease.

PMID- 15519032
TI  - Troponin and outcomes.

PMID- 15519034
TI  - The diet-heart hypothesis: an evolutionary support.

PMID- 15519037
TI  - Intercellular signaling between adipose tissue and muscle tissue.
AB  - Adipose and muscle tissues undergo regulated growth and differentiation processes
      that are modulated by a wide range of factors. The interactions between myogenic
      cells and adipocytes play a significant role in growth and development, including
      the rate and extent of myogenesis, muscle growth, adipogenesis,
      lipogenesis/lipolysis, and in the utilization of energy substrates. Important
      hormones and growth factors involved in the regulation of these processes include
      glucocorticoids, insulin-like growth factors, various cytokines, insulin, and
      leptin. Interactions among these axes have important implications in their
      influence on relative fat and lean deposition and the efficiency of energy
      utilization in growth and development. As research progresses to better clarify
      the interactions among adipose tissue depots and muscle of different fiber types,
      pathways will become better understood, ultimately leading to the optimized
      management of fat and lean growth in domestic livestock species. This review will
      focus on elements of intercellular signaling, using data from cell culture
      studies to illustrate specific examples of signaling pathways between cells.

PMID- 15519038
TI  - Plasma concentrations of inhibin A in cattle with follicular cysts: relationships
      with turnover of follicular waves and plasma levels of gonadotropins and steroid
      hormones.
AB  - We investigated the profiles of circulating levels of inhibin A and total inhibin
      in beef cows with follicular cysts in relation to the patterns of follicular
      development and circulating gonadotropins and steroid hormones. Turnover of
      follicular waves was monitored in five cows every 2 days for 70 days from 10 days
      after detection of estrus without ovulation. The mean interwave intervals were
      19.6 +/- 1.0 days (n = 18 waves with cysts from the five cows). Circulating
      levels of inhibin A were approximately 170 pg/ml before emergence of follicular
      waves with cysts and increased (P < 0.05) concomitantly with follicle emergence.
      High concentrations of inhibin A (greater than 300 pg/ml) were noted for 7 days
      during the growth phase of cystic follicles, but inhibin A levels decreased
      gradually when development of the cysts reached a plateau. This profile of
      inhibin A was similar to those of total inhibin and estradiol, but was inversely
      related to the changes in plasma FSH concentrations. LH pulse frequency and mean
      concentrations of LH in cows with cysts were higher than those observed in the
      luteal phase of normal cyclic cows. These results indicate that the capacity to
      secrete inhibin, as well as estradiol, is maintained in cystic follicles, the
      growth of which is extended by LH secretion at levels greater than those seen in
      the normal luteal phase. Inhibin A plays an important role in the extension of
      interwave intervals by suppressing recruitment of a new cohort of follicles.

PMID- 15519039
TI  - Mammary uptake and excretion of prostanoids in relation to mammary blood flow and
      milk yield during pregnancy-lactation and somatotropin treatment in dairy goats.
AB  - Mammary arterious-venous differences (A-V) and excretion into milk of four
      prostanoids were related to changes in milk yield and milk vein blood velocity
      (MBV) in goats at different stages of pregnancy and lactation, and during
      somatotropin (ST) treatment in mid-lactation. Arterial concentrations and mammary
      A-V for the vasodilators prostacyclin (PGI(2)) and prostaglandin (PG) E(2)
      (measured as 6-keto-PGF(1 alpha) and bicyclic PGE(2), respectively) decreased
      from late pregnancy to lactation. A-V were negatively correlated to MBV (r = 
      0.32 to -0.34). Arterial concentrations of the vasoconstrictors PGF(2 alpha) and
      TXA(2) (measured as TXB(2)) changed similarly, but no A-V across the mammary
      gland were found. The vasodilator to vasoconstrictor ratio in plasma was around
      1:1, and in skimmed milk around 0.29-0.49 due to significantly higher TXB(2)
      levels in milk compared to plasma. Close linear correlations were established
      between milk yield and excretion of TXB(2) into milk (r = 0.80, P < 0.001), and
      between MBV and PGE(2) excretion into milk (r = 0.69, P < 0.001). ST treatment
      stimulated MBV and mammary prostanoid supply, and decreased prostanoid
      concentration in milk vein plasma. The high arterial levels of prostaglandins
      during pregnancy most likely reflected uterine synthesis. Our results support a
      role for PGI(2) and PGE(2) in local mammary blood flow regulation during
      lactation. Increased mammary uptake of these two prostanoids may be involved in
      the mammary blood flow response to ST. TXA(2) may be synthesized by mammary
      epithelial as well as vascular cells, and TXA(2) may be an important factor in
      regulation of mammary function.

PMID- 15519040
TI  - Growth hormone increases Stat5 and Stat1 expression in lactating goat mammary
      gland: a specific effect compared to milking frequency.
AB  - In ruminants, both milking frequency and exogenous GH treatment affect milk
      production. In a previous report, we showed that the modulation of milk yield due
      to variations in milking frequency and GH treatment was associated with
      variations in mammary cell numbers. The aim of this study was to clarify the
      different mechanisms governing the effects of GH treatment and milking frequency
      on signal transducer and activator of transcription (Stat) expression and
      activation, and on the expression of genes involved in mammary cell
      differentiation. Six Saanen goats in late lactation were milked once daily from
      one half-udder and thrice daily from the other half-udder for 23 days. At the
      same time, the goats were divided into two groups: GH-treated versus control
      group. After slaughter of the goats, soluble mammary proteins and RNA were
      extracted from half-udder samples. Levels of Stat5, Stat3 and Stat1 proteins and
      the Stat activation by phosphorylation were analysed by Western blot. The amounts
      of Stat5 protein and mRNA were significantly elevated by GH treatment in all half
      udders (milked once or thrice daily). Positive Stat5 immunoreactivity was
      principally localised in the nuclei of epithelial cells, with heterogeneous
      intensity between cells. No significant changes in Stat5 protein phosphorylation
      levels were observed. Furthermore, GH significantly increased Stat1 protein
      levels, without modifying the level of Stat1 tyrosine phosphorylation, and tended
      to reduce the abundance of Stat3 protein. In contrast, milking frequency failed
      to modify Stat gene expression, protein level and phosphorylation. Using Northern
      blot, we showed that levels of kappa casein and prolactin receptor mRNA were not
      affected by the treatments. These observations suggest that GH probably acts
      specifically on mammary cells by regulating the expression of Stat1, 3 and 5. In
      contrast, milking frequency does not act through this regulatory pathway.

PMID- 15519041
TI  - The response of phospholipase C/protein kinase C and adenylyl cyclase/protein
      kinase A pathways in porcine theca interna cells to opioid agonist FK 33-824.
AB  - Opioids were found as factors affecting porcine ovarian steroidogenesis. The
      mechanism of opioid action, however, on porcine theca interna cells is completely
      unknown. Therefore, the present study was designed to investigate the possible
      involvement of two intracellular pathways, phospholipase C/protein kinase C and
      adenylyl cyclase/protein kinase A, in opioid signal transduction in porcine theca
      cells treated with mu opioid receptor agonist, FK 33-824. Incubation of the cells
      for 4 h with FK 33-824 at the dose 1 nM resulted in decreases in inositol
      phosphate accumulation as well as androstenedione (A(4)), testosterone (T), and
      estradiol (E(2)) secretions. Protein kinase C (PKC) inhibitors, staurosporine (1
      100 nM), D-sphingosine (10-500 nM), and PKCi (100-2000 nM), both added alone and
      together with the opioid agonist, depressed release of the steroid hormones. PKC
      activator, phorbol ester (PMA, 1-100 nM), used alone was without effect on theca
      cell steroidogenesis, but added in combination with FK 33-824 abolished
      inhibitory influence of the opioid on A(4), T, and E(2) output. The steroid
      hormone secretion by PKC-deficient theca cells was inhibited by the opioid
      agonist. FK 33-824 also suppressed PKC activity reducing [(3)H]PDBu specific
      binding to theca cells, whereas ionomycin (a positive control) increased labeled
      phorbol ester binding to the cells. In the next experiment, cAMP release from
      theca cells during 2 and 4 h incubations with FK 33-824 (1-100 nM), naloxone (10
      microM; opioid receptor antagonist), and LH (100 ng/mL; a positive control) was
      examined. FK 33-824 at the dose 1 nM inhibited cAMP secretion during 2 h
      incubation, but had no effect during longer incubation. LH in a manner
      independent on incubation time multiplied cAMP release. Protein kinase A
      inhibitor, PKAi (100-2000 nM), alone and in combination with FK 33-824 (1 nM),
      inhibited A(4), T, and E(2) secretions by theca cells. PKA activator, 8BrcAMP (10
      1000 microM), stimulated the steroid hormone release, but this stimulatory effect
      was diminished in the presence of FK 33-824. The results allow to suggest that
      opioid peptides affect porcine theca cell steroidogenesis and their acute action
      on the cells is connected with the inhibition of phospholipase C/protein kinase C
      and adenylyl cyclase/protein kinase A signal transduction systems.

PMID- 15519042
TI  - Differential expression of bone morphogenetic protein 4-6 (BMP-4, -5, and -6) and
      growth differentiation factor-9 (GDF-9) during ovarian development in neonatal
      pigs.
AB  - Growth differentiation factor-9 (GDF-9) and bone morphogenetic proteins (BMPs),
      comprise the largest subgroups of ligands in the TGF-beta superfamily, and have
      been shown to be involved in follicle development in mammals. However, whether
      these factors are involved in folliculogenesis in pigs is still unknown. The
      present study was performed to determine the relationships between early
      folliculogenesis and the expression of GDF-9 and BMP (BMP-4, -5 and -6) mRNAs in
      neonatal pigs. Ovaries were removed at 5, 16, 28 and 39 days after birth to
      examine the follicular population (the right ovary of each animal) and to detect
      mRNA expression (the left ovary of each animal). Primordial follicles accounted
      for >80% of the ovarian follicles from 5 days until 39 days after birth. A marked
      increase in primary follicles and the appearance of secondary follicles were
      observed in the ovaries at 28 days after birth. BMP-4, -5, and -6 and GDF-9 mRNAs
      were expressed by ovaries at 5-, 16-, 28- and 39-day-old pigs. The peak
      expression of BMP-4, -5, and -6 and GDF-9 mRNAs was observed in the ovaries at 5,
      39, 28 and 16 days, respectively, after birth. These data demonstrate that
      folliculogenesis in piglets might be controlled by the interaction with these
      factors. We conclude that BMPs and GDF-9 may have distinct functions in several
      stages of follicle development in neonatal pig ovaries.

PMID- 15519043
TI  - Expression of IglC is necessary for intracellular growth and induction of
      apoptosis in murine macrophages by Francisella tularensis.
AB  - Francisella tularensis is a facultative intracellular bacterium capable of
      inducing apoptosis in murine macrophages. In a previous study, an iglC null
      mutant of F. tularensis live vaccine strain LVS was generated by allelic
      replacement and in the current study this iglC mutant was successfully
      complemented in trans. We characterized the capacity of this iglC mutant and the
      complemented strain to induce macrophage apoptosis. The iglC mutant did not
      induce apoptosis in the infected cells. In contrast, the complemented iglC strain
      was able to multiply in the murine macrophage-like cell line J774A.1 and induced
      apoptosis similar to that of the wild-type strain. It is the first successful
      example of complementation in trans of a F. tularensis mutant strain and more
      importantly this work provides direct evidence that the intracellular growth
      ability is essential for F. tularensis to induce macrophage apoptosis.

PMID- 15519044
TI  - Ecto-ATPases of clinical and non-clinical isolates of Acanthamoeba.
AB  - Acanthamoeba are opportunistic protozoan parasites that can cause fatal
      granulomatous amoebic encephalitis and eye keratitis, however the pathogenic
      mechanisms of Acanthamoeba remain unclear. In this study, we described the
      ability of live Acanthamoeba to hydrolyse extracellular ATP. Both clinical and
      non-clinical isolates belonging to genotypes, T1, T2, T3, T4 and T7 exhibited
      ecto-ATPase activities in vitro. Using non-denaturing polyacrylamide gel
      electrophoresis, ecto-ATPases were further characterized. All Acanthamoeba
      isolates tested, exhibited a single ecto-ATPase band (approximate molecular
      weight of 272 kDa). However, clinical isolates exhibited additional bands
      suggesting that ecto-ATPases may play a role in the pathogenesis of Acanthamoeba.
      This was supported using suramin (ecto-ATPase inhibitor), which inhibited
      Acanthamoeba-induced host cell cytotoxicity. Previously, we and others have shown
      that Acanthamoeba binds to host cells using their mannose-binding protein and
      binding can be blocked using exogenous alpha-mannose. In this study, we observed
      that alpha-mannose significantly increased ecto-ATPase activities of pathogenic
      Acanthamoeba belonging to T1, T2, T3 and T4 genotypes but had no effect on non
      pathogenic Acanthamoeba (belonging to T7 genotype). Overall, we have shown, for
      the first time, that Acanthamoeba exhibit ecto-ATPase activities, which may play
      a role in the pathogenesis of Acanthamoeba as well as their potential role in the
      differentiation of pathogenic Acanthamoeba.

PMID- 15519045
TI  - The role of integrase/recombinase xerD and monofunctional biosynthesis
      peptidoglycan transglycosylase genes in the pathogenicity of Brucella abortus
      infection in vitro and in vivo.
AB  - Brucella abortus clones identified previously using a green fluorescence protein
      reporter system after 4h macrophage infection provided insight regarding possible
      genes involved in early host-pathogen interaction. Among identified genes were an
      integrase/recombinase (xerD) gene involved in cell division, and a monofunctional
      biosynthesis peptidoglycan transglycosylase (mtgA) gene that catalyzes the final
      stages of the peptidoglycan membrane synthesis. Here, we evaluate the in vitro
      and in vivo survival of B. abortus xerD and mtgA insertional mutants. B. abortus
      xerD::kan and B. abortus mtgA::kan demonstrated no significant growth defects in
      broth culture when compared to the parental strain, S2308. Also, neither gene was
      required for B. abortus S2308 replication in RAW 264.7 macrophages. However,
      experimental evidence using interferon regulatory factor 1 knockout mice, a mouse
      strain highly susceptible to virulent Brucella, revealed that mice infected with
      B. abortus xerD::kan or B. abortus mtgA::kan survived longer than mice infected
      with S2308. Additionally, in immunocompetent BALB/c mice, B. abortus xerD::kan
      had a significantly lower level of bacterial survival when compared to S2308.
      Together, these results suggest that B. abortus xerD and mtgA genes play a role
      during the initial phase of infection in mice.

PMID- 15519046
TI  - Endothelial cells from bovine pulmonary microvasculature respond to Mycoplasma
      bovis preferentially with signals for mononuclear cell transmigration.
AB  - Mycoplasma bovis can cause arthritis or mastitis following pneumonia and
      mycoplasmemia in cattle. Interactions with pulmonary vascular endothelium have
      been recorded as localized vasculitis, perivascular mononuclear cell
      infiltrations, and accumulation of inflammatory cells in lesions. We compared
      adhesion mediators and cytokine gene expression as well as cytotoxicity of
      cultured primary bovine aortic and bovine pulmonary microvascular endothelial
      cells (BPMEC) challenged with M. bovis. We also tested if abscess-forming ability
      of strains of M. bovis is associated with changes on endothelial cells. Increased
      VCAM-1 surface expression was found in both cell types, while only infected BPMEC
      increased MCP-1 transcription, both mediators specific for mononuclear cell
      transmigration. Given no induction of ICAM-1 mRNA in either cell type, induction
      of IL-8 mRNA by BPMEC suggested that neutrophil transmigration was signaled in
      microvascular areas. Infected BPMEC showed early induction of IL-1beta and IL-6
      mRNA. Excepting VCAM-1, differential strain effects were limited to BPMEC and not
      correlated with their abscess-forming capability. In addition, only strain DSA16
      had minor cytotoxic effect on both cell types. We thus show that BPMEC are more
      susceptible than aortic cells to M. bovis-induced activation. Activation
      preferentially yielded signals for mononuclear cell transmigration, correlating
      well with in vivo observations of infiltrating cells at pulmonary sites.

PMID- 15519047
TI  - Inhibition of bovine macrophage and polymorphonuclear leukocyte superoxide anion
      production by Haemophilus somnus.
AB  - Virulent strains of the bovine opportunistic pathogen Haemophilus somnus
      (Histophilus somni) cause multi-systemic diseases in cattle. One of the reported
      virulence factors that H. somnus may use to persist in the host is resistance to
      intracellular killing. We report here that H. somnus significantly (P < 0.001)
      inhibited production of superoxide anion (O2-) by bovine mammary and alveolar
      macrophages as well as by polymorphonuclear leukocytes. Inhibition of O2- was
      time- and dose-dependent and did not occur after incubation with Escherichia
      coli, H. influenzae, or Brucella abortus. Non-viable H. somnus, purified
      lipooligosaccharide, or cell-free supernatant from mid-log phase cultures did not
      inhibit O2- production, indicating that O2- inhibition required contact with live
      H. somnus. Furthermore, preincubation of phagocytic cells with cytochalasin B to
      prevent phagocytosis did not decrease the ability of H. somnus to inhibit O2-
      production. Some H. somnus isolates from the prepuce of healthy bulls were less
      capable or incapable of inhibiting macrophage O2- production compared to isolates
      tested from disease sites. Our results suggest that inhibition of O2- may be an
      important virulence factor exploited by pathogenic strains of H. somnus to resist
      killing by professional phagocytic cells.

PMID- 15519048
TI  - Parasite-derived trans-sialidase binds to heart tissue in Trypanosoma cruzi
      infected animals.
AB  - Trypanosoma cruzi is an obligate intracellular protozoan parasite that actively
      penetrates into non-phagocytic mammalian cells. To accomplish this, the parasite
      relies on the binding of cell surface ligands. It is reported herein that the T.
      cruzi trans-sialidase (TS), which is exposed on the parasite surface, binds to
      mouse heart cells, and should therefore be further studied as a possible cell
      penetration-related ligand. In addition, as has been proposed elsewhere, the
      binding of T. cruzi to tissues may turn them into targets for parasite-specific
      immune reactions. Washed heart sections from T. cruzi-infected mice were
      subjected to immunoenzymatic staining with antisera against whole T. cruzi and
      with polyclonal or monoclonal antibodies against TS. The anti-TS antibodies
      stained both parasites and uninfected heart cells in the vicinity of T. cruzi
      nest remains/trypomastigotes. On the other hand, an anti-T. cruzi serum, which
      did not recognize TS, only stained the parasites. In addition, normal heart
      sections from uninfected nude mice were shown to react with both enzymatically
      active and inactive recombinant TS molecules, probably through their amino
      terminal region, since a recombinant TS lacking this region failed to bind.

PMID- 15519049
TI  - Cataract formation after implantation of myopic phakic posterior chamber IOLs.

PMID- 15519050
TI  - Improved functional vision with a modified prolate IOL.

PMID- 15519053
TI  - Subjective and objective measurement of human accommodative amplitude.

PMID- 15519055
TI  - Residual bed thickness and corneal forward shift after laser in situ
      keratomileusis.

PMID- 15519056
TI  - Small-gauge, sutureless pars plana vitrectomy to manage vitreous loss during
      phacoemulsification.

PMID- 15519058
TI  - Pseudophakic preoperative maculopathy.

PMID- 15519059
TI  - Effect of diclofenac versus dexamethasone on posterior capsule opacification.

PMID- 15519061
TI  - Tissue plasminogen activator in the management of anterior chamber fibrin
      formation.

PMID- 15519065
TI  - Aqueous humor levels of topically applied bupivacaine 0.75% in cataract surgery.

PMID- 15519066
TI  - Bilateral keratectasia after laser in situ keratomileusis.

PMID- 15519067
TI  - Effect of environmental factors on myopic laser in situ keratomileusis
      enhancement rates.

PMID- 15519068
TI  - Consultation section. Refractive surgical problem.

PMID- 15519072
TI  - Irrigating chopper and vacuum capsulorhexis: a new technique in
      phacoemulsification.
AB  - A continuous curvilinear capsulorhexis (CCC) technique for cataract extraction
      surgery by phacoemulsification is described. The technique replaces a forceps or
      needles with vacuum traction and further modifies vacuum capsulorhexis. The
      technique was performed in 30 patients. The achieved CCCs were compared with the
      desired CCC of approximately 6.0 mm (range 5.8 to 6.2 mm). The desired CCC was
      achieved in 19 patients; 7 patients had a smaller-diameter CCC and 2, a larger
      than-desired diameter. Two patients had partial capsule tear. The mean diameter
      was 5.79 mm +/- 0.57 (SD). This technique allows CCC to be performed through
      small incisions (1.0 mm) without the use of ophthalmic viscosurgical devices.

PMID- 15519073
TI  - Modifications in cataract surgery for the morbidly obese patient.
AB  - We describe a standing phacoemulsification technique (SPT) with the patient in
      reverse Trendelenburg position (RTP) as a means of performing surgery in morbidly
      obese patients. These patients have elevated vitreous pressure, leading to a high
      rate of posterior capsule rupture and vitreous loss. The SPT with RTP normalizes
      vitreous pressure, facilitating cataract surgery.

PMID- 15519074
TI  - Long-term results of implantation of phakic posterior chamber intraocular lenses.
AB  - PURPOSE: To study the incidence and progression of lens opacification after
      implantation of phakic posterior chamber intraocular lenses for myopia and its
      correlation with vaulting and endothelial cell density (ECD). SETTING: Department
      of Ophthalmology, University of Vienna Medical School, Vienna, Austria. METHODS:
      An implantable contact lens (ICL V4, Staar Surgical Inc.) was inserted in 76
      myopic eyes. Patients were prospectively followed preoperatively and at 1, 3, 6,
      12, 24, and 36 months. The uncorrected visual acuity and best corrected visual
      acuity (BCVA) were determined. Vaulting was measured optically with a Jaeger II
      pachymeter, and the crystalline lens was examined at the slitlamp for the
      presence and characteristics of opacification. Endothelial cell morphometry was
      performed by specular microscopy, and the ECD was calculated. Eyes in which lens
      opacification developed were followed for at least 12 months to determine the
      degree and course of visual impairment. RESULTS: Lens opacification occurred in
      11 eyes (14.5%). Opacification was correlated with intraoperative trauma to the
      crystalline lens, age older than 50 years, and decreased ECD values throughout
      the observation period. Vaulting of the ICL did not correlate with the risk for
      lens opacification. After onset of lens opacification, 6 eyes (55%) had a stable
      BCVA within +/-0.5 lines and 5 eyes had progressive opacification, losing between
      3.5 lines and 0.5 lines (mean 1.8 lines +/- 1.1 [SD]). Three eyes (3.9%) in the
      progressive group had a 1- to 2-line loss of BCVA over preoperative values and
      subsequently had cataract surgery. CONCLUSIONS: Risk factors for lens
      opacification after implantation of the model V4 ICL included intraoperative
      trauma to the crystalline lens and older age. Decreased ECD in eyes with
      opacification suggests ongoing inflammation as a cause. Patients younger than 45
      years may have a significantly lower incidence of opacification.

PMID- 15519075
TI  - Phakic posterior chamber intraocular lens for high myopia.
AB  - PURPOSE: To evaluate the efficacy, predictability, stability, and safety of the
      surgical correction of high myopia using a phakic posterior chamber intraocular
      lens (PPC IOL). SETTING: Centro Oftalmologico de Valencia-CEOVAL, Valencia,
      Venezuela. METHODS: A retrospective study was performed to analyze 18 eyes of 12
      patients who had implantation of a modified PPC IOL, the implantable contact lens
      (ICL), for the treatment of high myopia. The target postoperative spherical
      equivalent (SE) refraction was emmetropia. RESULTS: The mean follow-up was 26.6
      months +/- 11.3 (SD) (range 12 to 36 months). The mean preoperative SE was -15.27
      +/- 3.47 diopters (D) (range -10.0 to -21.25 D) and the mean postoperative SE, 
      0.62 +/- 0.81 D (range -2.75 to +0.75 D). Eleven eyes (61.1%) had an SE within +/
      1.00 D of emmetropia. The best spectacle-corrected visual acuity was maintained
      or improved in all except 1 eye, which lost more than 2 lines of Snellen visual
      acuity. Two eyes (11.1%) developed pupillary block the first day after surgery.
      Four eyes (22.2%) had moderate pigmentary dispersion. Two eyes (11.1%) had lens
      opacification, 1 with mild peripheral anterior capsule opacification and the
      other eye with central anterior subcapsular opacification. One eye (5.5%) had a
      significant decrease in anterior chamber depth after surgery. CONCLUSIONS:
      Implantation of an ICL was effective for the correction of high myopia.
      Predictability must be improved and the long-term safety of the ICL determined.
      The main concerns over potential cataract formation, pigmentary dispersion, and
      angle-closure glaucoma remain.

PMID- 15519076
TI  - Contrast sensitivity after implantation of toric iris-claw lenses in phakic eyes.
AB  - PURPOSE: To evaluate the change in contrast sensitivity after implantation of the
      Verisyse toric phakic intraocular lens (IOL) (AMO) for the correction of myopia
      with astigmatism. SETTING: Department of Ophthalmology, Johannes Gutenberg
      University, Mainz, Germany. METHODS: Eighteen eyes had implantation of an iris
      supported toric phakic IOL to correct myopia with astigmatism. The mean
      preoperative spherical equivalent was -12.65 diopters +/- 3.6 (SD). The contrast
      sensitivity with best spectacle correction was determined before surgery and 3
      months after surgery using the CSV-1000 HGT instrument (Vector Vision Inc.).
      RESULTS: Three months after IOL implantation, the mean contrast sensitivity had
      significantly increased from preoperatively at midrange spatial frequencies from
      3.2 to 4.4 (6 cycles per degree [cpd]; P = .033) and from 2.4 to 3.7 (12 cpd; P =
      .032). The differences at spatial frequencies of 3 cpd and 18 cpd were not
      statistically significant (P = .59 and P = .086, respectively). CONCLUSIONS:
      Implantation of the Verisyse toric iris-claw lens in phakic eyes to correct high
      or moderate myopia with astigmatism has the potential to improve contrast vision.
      The mean contrast sensitivity increased considerably at all spatial frequencies
      compared with preoperative levels.

PMID- 15519077
TI  - Predicting time to refractive stability after discontinuation of rigid contact
      lens wear before refractive surgery.
AB  - PURPOSE: To determine whether discontinuing rigid contact lenses for 3 weeks is
      sufficient to achieve refractive stability and if not, to identify factors,
      including indicators of corneal warpage, that are associated with prolonged
      corneal instability. SETTING: University-based refractive surgery practice.
      METHODS: Charts of patients seen for refractive surgery consultation from January
      1999 to March 2001 were reviewed. Patients with a history of rigid gas-permeable
      (RGP) contact lens use were identified and instructed to discontinue wearing
      lenses 3 weeks before the initial examination. Patients were examined at 3-week
      intervals until a stable refraction was achieved (within +/-0.25 diopter [D]
      sphere and 0.25 D cylinder with less than 25 degrees of axis orientation). Visual
      acuity, subjective refraction, and corneal topography were obtained at each
      visit. RESULTS: Of 55 eyes of 28 patients, 31 eyes achieved refractive stability
      by the second visit (early-stability group) and 24 eyes required more than 2
      visits to achieve stability (late-stability group). No statistically significant
      between-group difference was observed in age, sex, refractive cylinder,
      topographic cylinder, difference between refractive and topographic cylinders,
      surface regularity index, surface asymmetry index, or spherical equivalent at the
      initial examination. The number of years of contact lens wear was significantly
      different between the groups (P = .05). CONCLUSIONS: The time for contact lens
      induced corneal changes to reach a steady state after cessation of lens wear is
      highly variable. Among the variables examined, including those indicating corneal
      warpage, the factor that correlated with the required time to refractive
      stability after discontinuation of RGP wear was the length of time of contact
      lens use. Patients who are long-term RGP wearers should be counseled that
      multiple visits will likely be required before a stable refraction is obtained.

PMID- 15519078
TI  - Flap and stromal bed thickness in laser in situ keratomileusis enhancement.
AB  - PURPOSE: To evaluate whether flap thickness changes after the primary laser in
      situ keratomileusis (LASIK) procedure and to assess the accuracy of
      intraoperative pachymetry and ablation depth measurements in predicting stromal
      bed thickness before enhancement in eyes that have had primary myopic LASIK.
      SETTING: Bascom Palmer Eye Institute, Miami, Florida, USA. METHODS: This
      retrospective noncomparative interventional case series comprised 57 eyes of 42
      patients who had LASIK enhancement between June 2001 and September 2002.
      Exclusion criteria included previous ocular surgery or complications during the
      first LASIK procedure. Only patients who had had LASIK and enhancement by the
      same surgeon at our institution and had intraoperative pachymetry readings for
      both procedures were included. The original flap was relifted in all enhancement
      procedures. Corneal thickness was routinely measured intraoperatively by
      ultrasound pachymetry. The age, eye, refraction, date of primary LASIK, central
      corneal thickness (CCT) and central stromal bed thickness at primary LASIK, depth
      of ablation, flap thickness (subtraction pachymetry), date of enhancement, CCT
      and central stromal bed thickness at enhancement, and flap thickness at
      enhancement were recorded. RESULTS: Thirty-one eyes of 26 patients were myopic
      and 26 eyes of 16 patients were hyperopic before primary LASIK. The mean time
      between LASIK and enhancement was 218 days +/- 115 (SD) (193 +/- 88 days in
      myopic eyes and 248 +/- 136 days in hyperopic eyes [P = .068]). The flap tended
      to be thicker at enhancement than in the primary LASIK procedure by 9.3 +/- 25.7
      microm in myopic eyes (P = .054) and 10.5 +/- 16.6 microm in hyperopic eyes (P =
      .004). A strong correlation was found between flap thickness in the first and
      second procedures in myopic and hyperopic eyes (r = 0.6). In myopic eyes, the
      mean difference between the estimated stromal bed thickness after the first
      procedure (central bed thickness- ablation depth) and the stromal bed thickness
      measured directly at enhancement was not statistically significant (3 +/- 29
      microm; P = .54, paired t test). A strong correlation was found between the 2
      measurements (r = 0.8, P<.001). Another strong correlation was found in myopic
      eyes between the estimated corneal thickness after the primary LASIK and the
      corneal thickness measured at enhancement (r = 0.81, P<.001). No correlation was
      found between the difference in flap thickness and the time to enhancement (r =
      0.09 in myopic eyes and r = 0.01 in hyperopic eyes). CONCLUSIONS: Flap thickness
      tended to be thicker at enhancement than at primary LASIK. Intraoperative
      pachymetry and ablation depth measurements proved to be precise tools to predict
      stromal bed thickness before enhancement in eyes that had had primary myopic
      LASIK. This information may help in planning LASIK enhancements.

PMID- 15519079
TI  - Laser in situ keratomileusis to correct post-keratoplasty astigmatism; 1-step
      versus 2-step procedure.
AB  - PURPOSE: To investigate the correction of post-penetrating keratoplasty (PKP)
      astigmatism using laser in situ keratomileusis (LASIK). Visual and refractive
      outcomes were evaluated after LASIK was performed in 1 step (lamellar cut and
      ablation in 1 procedure) or 2 steps (lamellar cut then ablation in 2 successive
      procedures). SETTING: Department of Cornea and Refractive Surgery, Vissum
      Instituto Oftalmologico de Alicante, University of Miguel Hernandez, Alicante,
      Spain. METHODS: In this prospective observational study, 22 consecutive eyes were
      divided into 2 groups depending on the LASIK procedure performed to correct post
      PKP astigmatism. Group 1 (1-step LASIK) included 11 eyes and Group 2 (2-step
      LASIK), 11 eyes. The patients were followed for 6 months. RESULTS: A
      statistically significant improvement was obtained in Group 2 with a mean vector
      analysis result of the cylinder of -4.37 diopters (D) +/- 1.79 (SD) (P = .018).
      In Group 1, the mean astigmatism correction was 2.38 +/- 1.71 D. The number of
      reoperations and residual refractive defects were significantly better in Group
      2. CONCLUSION: The 2-step technique improved the accuracy of excimer laser
      correction of post-PKP astigmatism.

PMID- 15519080
TI  - Effect of preoperative tear function on early functional visual acuity after
      laser in situ keratomileusis.
AB  - PURPOSE: To assess the effect of preoperative tear function on early changes in
      functional visual acuity (FVA) after laser in situ keratomileusis (LASIK).
      SETTING: Minamiaoyama Eye Clinic, Tokyo, Japan. METHODS: This prospective single
      center study assessed the effect of preoperative and postoperative tear functions
      on FVA in 30 eyes of 15 patients who had LASIK. Functional visual acuity was
      defined as the binocular recognition acuity measured by the FVA tester
      (Wellsystem) during a 10-second, blink-free period. All patients had a Schirmer
      test with anesthesia and tear-film breakup time (BUT) measurements preoperatively
      and 1 day and 1 week after LASIK. Corneal topography and Landolt visual acuity
      and FVA measurements were performed before surgery and 1 day and 1 week after
      LASIK. Eyes with a Schirmer test reading less than 5.0 mm and a BUT less than 5
      seconds were grouped as definite dry eye (DDE). Eyes with a normal Schirmer test
      score but a shortened BUT were grouped as probable dry eye (PDE). RESULTS: In all
      patients, the best uncorrected Landolt visual acuity was 20/20 or better at the
      postoperative examination times. In the DDE group, the mean preoperative FVA
      declined from 1.2 to 0.75 +/- 0.16 (SD) at 1 day and increased to 1.2 at 1 week.
      No change in FVA was observed postoperatively in the PDE group. CONCLUSION: Laser
      in situ keratomileusis patients with low basal tearing and full uncorrected
      distance Landolt acuity may experience a transient decrease in FVA that returns
      to baseline within 1 week.

PMID- 15519081
TI  - Early changes in corneal sensation, ocular surface integrity, and tear-film
      function after laser-assisted subepithelial keratectomy.
AB  - PURPOSE: To investigate the changes in corneal sensation, ocular surface
      integrity, and tear-film function after laser-assisted subepithelial keratectomy
      (LASEK). SETTING: Department of Ophthalmology, University of Graz, Graz, Austria.
      METHODS: Laser-assisted subepithelial keratectomy was performed in 21 consecutive
      patients (37 myopic eyes). The patients were observed for subjective complaints
      of dry eye, corneal sensation, tear-film breakup time (BUT), Schirmer test
      without local anesthesia, and fluorescein and lissamin-green staining
      preoperatively and 1 week and 1, 3, and 6 months postoperatively. RESULTS: The
      subjective score for dry-eye symptoms was not statistically significantly higher
      after the procedure. Corneal sensation was reduced up to 1 month after LASEK
      (P<.05). There were obvious decreases in BUT at 1 week and 1 month (P<.01) and no
      significant changes in Schirmer test results. In fluorescein staining of the
      cornea, dots were more concentrated at 1 week (P<.05). In lissamin-green
      staining, no significant changes were found at any follow-up examination.
      CONCLUSIONS: Laser-assisted subepithelial keratectomy induced a short-term
      reduction in corneal sensation and affected the ocular surface and tear film
      slightly. Epithelial flap repositioning in LASEK may have a positive influence on
      tear-film and ocular-surface factors.

PMID- 15519082
TI  - Effect of anterior capsule polishing on fibrotic capsule opacification: three
      year results.
AB  - PURPOSE: To evaluate the long-term effect of anterior capsule polishing on
      anterior capsule opacification (ACO) and peripheral fibrotic posterior capsule
      opacification (PCO). SETTING: Department of Ophthalmology, Medical University of
      Vienna, Vienna, Austria. METHODS: This randomized double-blind study comprised
      104 eyes of 52 patients with bilateral age-related cataract. All patients
      received round-edged intraocular lenses (IOLs); 26 received an SI-40 IOL
      (Advanced Medical Optics Inc.) in both eyes, and 26 received a Silens6 IOL
      (Domilens) in both eyes. Both IOLs consist of different silicone material and
      have different haptic angulation. The SI-40 IOL has 13.0 mm open-loop poly(methyl
      methacrylate) (PMMA) haptics angulated by 10 degrees. The Silens6 IOL has 12.5 mm
      open-loop PMMA haptics with no angulation. In 1 eye, the anterior capsule was
      extensively polished. The anterior capsule was left unpolished in the
      contralateral eye, which acted as a control. Digital slitlamp photographs of the
      ACO and fibrotic PCO were taken with a standardized technique for 3 years
      postoperatively. The intensity of ACO was measured objectively (score 0% to 100%)
      using Adobe Photoshop software. Fibrotic PCO was graded subjectively (score 0 to
      4). RESULTS: The mean ACO was 17% in the polished eyes and 26% in the control
      eyes (P = .0001). The mean fibrotic PCO score was 0.5 and 1.0, respectively (P =
      .0007). The mean ACO was 15% in the polished SI-40 eyes and 26% in the control SI
      40 eyes (P = .01). It was 19% in the polished Silens6 eyes and 26% in the control
      Silens6 eyes (P = .003). The mean fibrotic PCO score was 0.4 in the polished SI
      40 eyes and 1.1 in the control SI-40 eyes (P = .0006). It was 0.6 in the polished
      Silens6 eyes and 0.9 in the control Silens6 eyes (P = .08). CONCLUSIONS: Three
      years after surgery, eyes in which the anterior capsule was extensively polished
      had less ACO and fibrotic PCO with both round-edged silicone IOLs. In eyes with
      Silens6 IOLs, however, the reduction in fibrotic PCO was not significant.

PMID- 15519083
TI  - Complications associated with anterior basement membrane dystrophy after laser in
      situ keratomileusis.
AB  - PURPOSE: To evaluate the complications associated with anterior basement membrane
      dystrophy (ABMD) after laser in situ keratomileusis (LASIK). SETTING: Cornea
      Service, Wills Eye Hospital, Jefferson Medical College, Thomas Jefferson
      University, Philadelphia, Pennsylvania, USA. METHODS: In this noncontrolled
      retrospective case series, the medical records of all patients with LASIK
      complications seen in the Cornea Service at Wills Eye Hospital from January 1,
      1998, to December 31, 2002, were reviewed. All patients who presented with ABMD
      changes after LASIK were included in the study. Patients with a history of trauma
      before or after surgery were excluded. RESULTS: Thirty-five eyes of 18 patients
      were included. The mean age was 46.2 years. Thirteen eyes (37.1%) had a flap-lift
      procedure to remove epithelial ingrowth or for an enhancement. The most common
      reason for the visit was visual complaints, which were seen in 77.8% of patients.
      Seven patients (38.9%) had visual complaints alone; 27.8% had visual complaints
      associated with recurrent erosions and 11.1%, with dry eyes. Four patients
      (22.2%) had recurrent corneal erosions with no visual complaints. On examination,
      the most common finding was negative staining with fluorescein dye within the
      LASIK flap, which was seen in all patients. In addition to the ABMD changes,
      25.7% had some degree of epithelial ingrowth and 45.7%, irregular astigmatism.
      CONCLUSIONS: Anterior basement membrane dystrophy changes post LASIK were
      associated with visual complaints and/or recurrent erosions. Patients should be
      carefully screened for ABMD. Those who have ABMD signs or symptoms may not be
      ideal candidates for LASIK.

PMID- 15519084
TI  - NeoSoniX ultrasound versus ultrasound alone for phacoemulsification: randomized
      clinical trial.
AB  - PURPOSE: To evaluate the difference in consumption of ultrasound (US) energy
      required with NeoSoniX (Alcon) in conjunction with US (NeoSonix US) versus US
      alone. SETTING: Iladevi Cataract & IOL Research Center, Ahmedabad, India.
      METHODS: This prospective randomized study comprised 120 consecutive eyes having
      phacoemulsification with the Alcon Legacy 20000 series at Iladevi Cataract & IOL
      Research Centre. Two groups of 60 eyes each were formed based on cataract grade
      according to the Emery classification: grade 2 and 3 nuclear sclerosis (Group A)
      and grade 4 and 5 nuclear sclerosis (Group B). In each group, 30 eyes had
      phacoemulsification using NeoSoniX US and 30 eyes, using US alone. The main
      parameters were intraoperative US time and mean US power. Effective phaco time
      (EPT) was calculated by multiplying the US time and mean US power and dividing
      the product by 100. The unpaired Student t test was used to evaluate the
      differences between NeoSoniX US and US alone. The corresponding 95% confidence
      intervals were calculated. RESULTS: In Group A, the mean US time was 106 seconds
      with NeoSoniX US and 144.30 seconds with US alone (P = .002), the mean US power
      was 13.50% and 15.83%, respectively (P = .059), and the mean EPT was 15.17
      seconds and 22.94 seconds, respectively (P = .006). In Group B, the mean US time
      was 193.67 seconds with NeoSoniX US and 255.17 seconds with US alone (P = .000),
      the mean US power was 18.31% and 22.76%, respectively (P = .000), and the mean
      EPT was 35.67 seconds and 59.15 seconds, respectively (P = .000). The EPT was
      33.5% and 39.6% less with NeoSoniX US than with US alone in Group A and Group B,
      respectively. CONCLUSIONS: Ultrasound energy consumption with NeoSoniX was
      significantly less than with US alone, indicating the value of NeoSoniX in
      emulsifying cataracts of optimum density and dense hard cataracts. Combining
      NeoSoniX and US significantly reduced the consumption of US energy.

PMID- 15519085
TI  - Effect of expanding the treatment zone of the Nidek EC-5000 laser on laser in
      situ keratomileusis outcomes.
AB  - PURPOSE: To evaluate the effect of expanding the treatment zone of the Nidek EC
      5000 laser on postoperative visual acuity as well as night glare and halos after
      laser in situ keratomileusis (LASIK) using 4 ablation zone diameters. SETTING:
      Division of Ophthalmology, Evanston Northwestern Healthcare and Northwestern
      University Medical School, Glenview, Illinois, USA. METHODS: This prospective
      study comprised 301 eyes of 154 consecutive patients who had LASIK in 1 or both
      eyes using the Nidek EC-5000 laser by 1 surgeon with experience in keratomileusis
      and excimer laser refractive surgery. A 6.5 mm optical zone was used with a
      transition zone 1.0 mm larger than the pupil under scotopic conditions (7.5, 8.0,
      8.5, or 9.0 mm). Targeted correction was calculated according to a customized
      clinical nomogram. All patients were queried about glare and halos preoperatively
      and 3 months postoperatively using a questionnaire assigning numeric values to
      the degree of perceived visual disturbance (0 = no glare or halos, 1 = minimal, 2
      = moderate, 3 = severe). RESULTS: The baseline uncorrected visual acuity (UCVA)
      was 20/200 or worse in 293 eyes. The baseline best spectacle-corrected visual
      acuity was 20/20 or better. The mean preoperative refractive sphere was -6.33
      diopters (D) +/- 2.80 (SD) (range -1.00 to -16.25 D) and the mean preoperative
      refractive cylinder, 0.86 +/- 0.83 D (range 0 to +3.25 D). Three months
      postoperatively, 78% of eyes had a UCVA of 20/20 and 99%, of 20/40 or better.
      Preoperatively, 94 eyes (31%) had glare and halos. At 3 months, glare, halos, or
      both were present in 19 eyes of 11 patients (6.3%) (P<.0001); in 14 eyes,
      patients reported less severe glare and halos postoperatively than
      preoperatively. CONCLUSIONS: The use of a peripheral transition zone 1.0 mm
      larger than the pupil under scotopic conditions resulted in a low incidence of
      glare and halos postoperatively and did not adversely affect visual acuity. There
      was no increase in postoperative complications including corneal ectasia.

PMID- 15519086
TI  - Performance of the Hansatome microsuction ring for laser in situ keratomileusis
      in eyes with narrow palpebral apertures.
AB  - PURPOSE: To evaluate the performance of a new microsuction ring during laser in
      situ keratomileusis (LASIK) in eyes with narrow palpebral apertures. SETTING:
      Singapore National Eye Centre, Singapore, Republic of Singapore. METHODS: Laser
      in situ keratomileusis was performed sequentially in both eyes of 33 Chinese
      patients. A randomization table was used to determine the control and test eyes.
      A standard suction ring (20.3 mm diameter) was used in control eyes, and a
      microsuction ring (19.0 mm diameter) was used in test eyes. Corneal flaps were
      created using the Hansatome microkeratome (Baush & Lomb). The following ring
      performance parameters were evaluated: flap diameter deviation (actual minus
      nominal flap diameter), ease of suction ring application, adequacy of suction,
      and overall microkeratome performance. Parameters 2 to 4 were rated by the
      surgeons using a subjective 1 to 100 scale. RESULTS: The mean flap diameter
      deviation was 0.45 mm in the control eyes and 0.22 mm in the study eyes; the mean
      difference was 0.23 mm (95% confidence interval, 0.39-0.07) (P<.001). For ease of
      application, the mean score of the microsuction ring was 100 and of the standard
      suction ring, 89.9. For adequacy of suction, the mean score of the microsuction
      ring was 99.7 and of the standard suction ring score, 98.2 (P = .13). The mean
      overall microkeratome performance score using the microsuction ring was 99.4 and
      using the standard suction ring, 94.6 (P = .011). CONCLUSION: The Hansatome
      microsuction ring was easy to apply during LASIK in eyes with narrow palpebral
      apertures, and there appeared to be no compromise of ring performance and safety.

PMID- 15519087
TI  - Predicting cataract surgery results using a macular function test.
AB  - PURPOSE: To assess the predictive value of a macular function test in the
      preoperative evaluation of cataract patients. SETTING: Clinique Generale St-Jean,
      Brussels, Belgium. METHODS: This prospective study comprised 396 uneventful
      consecutive cataract procedures performed by 1 surgeon from September 2000 to
      February 2001. The best corrected visual acuity (BCVA) and the density and
      location of the lens opacities were recorded preoperatively. Macular function was
      assessed preoperatively using a Parinaud test at 12 cm with a hyperaddition of
      +8.0 diopters and extra illumination. The postoperative BCVA was compared with
      the results of the macular function test. RESULTS: Of the 359 eyes (90.7%) that
      could read the Parinaud 1 line on the preoperative hyperaddition test, 338
      (94.2%) attained a final BCVA of 20/25 or better and 356 (99.2%), of 20/30 or
      better. Twenty-five eyes that could not read Parinaud 1 and presented with a
      dense nuclear or posterior subcapsular cataract also achieved a BCVA of 20/25 or
      better. Three eyes could read Parinaud 1 preoperatively but did not attain a BCVA
      of 20/30 or better postoperatively; 2 of the eyes had macular edema and 1, an
      opaque posterior capsule. CONCLUSIONS: The results of this study suggest that
      this simple macular function test has a positive predictive value of 94.2% in
      predicting a visual outcome of 20/25 or better after cataract surgery. The
      sensitivity was 94.2% and the specificity, 32.4%. The negative predictive value
      was 32.4% and the positive predictive value for a BCVA of 20/30 or better, 99.2%.

PMID- 15519088
TI  - Incidence of and risk factors for residual posterior capsule opacification after
      cataract surgery.
AB  - PURPOSE: To evaluate the incidence of and determine the risk factors for residual
      posterior capsule opacification (PCO). SETTING: University of New Mexico Health
      Sciences Center and the Veterans Administration Medical Center, Albuquerque, New
      Mexico, USA. METHODS: This study evaluated 194 uneventful cataract surgeries.
      Immature cataracts were graded for nuclear sclerosis (NS), posterior subcapsular
      cataract (PSC), and anterior cortical spokes on a 1 to 4 scale. Preoperative
      Snellen best corrected visual acuity was converted to the logMAR scale. The
      posterior capsule was examined after polishing and was classified as clear or as
      having residual opacity. Those with residual capsule opacity were evaluated 6
      weeks postoperatively for the presence of visually significant PCO. RESULTS: The
      incidence of residual capsule opacity was 23% (44 eyes). Seven (54%) of 13 eyes
      with white mature cataract had residual capsule opacity. In contrast, 37 (20%) of
      181 eyes with immature cataract had residual capsule opacity (P = .01). In eyes
      with immature cataract, the mean preoperative logMAR acuity was +1.14 +/- 0.60
      (SD) in the residual capsule opacity group and +0.73 +/- 0.46 in the clear group
      (P<.001). In eyes with immature cataract, the adjusted odds ratio for each
      increasing grade of NS was 2.3 and of PSC, 1.8 (P = .002 and P<.001,
      respectively). Eleven percent (5 eyes) of residual capsule opacities resulted in
      visually significant PCO 6 weeks postoperatively. All 5 opacities were centrally
      located at surgery. CONCLUSIONS: Results indicate that aggressive polishing of
      peripheral or adherent residual capsule opacities is not advisable as only 5 eyes
      with central residual capsule opacities developed visually significant PCO.

PMID- 15519089
TI  - Corneal edema and intraocular pressure after cataract surgery: randomized
      comparison of Healon5 and Amvisc Plus.
AB  - PURPOSE: To compare the protective effect of Healon5 (sodium hyaluronate 2.3%)
      and Amvisc Plus (sodium hyaluronate 1.6%) against corneal edema and their
      association with postoperative intraocular pressure (IOP) spikes in patients
      having phacoemulsification and intraocular lens (IOL) implantation. SETTING:
      Ophthalmology department of a general hospital. METHODS: One hundred forty
      patients were randomly assigned to have surgery with Healon5 (n = 70) or Amvisc
      Plus (n = 70). One eye of each patient was analyzed. Data collected
      preoperatively included best corrected visual acuity (BCVA) and IOP. Central
      ultrasonic pachymetry was performed in all patients. The same ophthalmologist
      performed all surgeries. The IOP and central corneal thickness (CCT) were
      measured 1 and 4 days and 1 month after surgery. The BCVA was also assessed at 1
      month. RESULTS: There were no significant preoperative differences between the
      Healon5 and Amvisc Plus groups in sex, age, ocular pathology, BCVA, IOP, or CCT.
      Intraoperative variables were similar between groups, but it took significantly
      longer to remove the Healon5. Postoperatively, there were no differences between
      groups in the evolution of CCT or of IOP. Intraocular pressure spikes over 30 mm
      Hg were detected at 1 day in 7 patients in the Healon5 group and 2 patients in
      the Amvisc Plus group (10.0% versus 2.9%; P = .165). CONCLUSIONS: Both OVDs were
      beneficial in a wide range of cataract patients. However, the results suggest a
      tendency toward a higher complication rate with Healon5.

PMID- 15519090
TI  - Efficacy of the soft-shell technique using Viscoat and Hyal-2000.
AB  - PURPOSE: To evaluate whether the soft-shell technique using Viscoat (sodium
      hyaluronate 3%-chondroitin sulfate 4%) and Hyal-2000 (sodium hyaluronate 1%)
      reduces corneal endothelial cell damage during cataract surgery. SETTING:
      Department of Ophthalmology, Kangnam St. Mary's Hospital, Seoul, Korea. METHODS:
      The nuclear opacity in 252 eyes of 230 cataract patients was classified as grade
      1, 2, 3, or > or =4 using the Lens Opacities Classification System III. In each
      classification, the patients were divided into 4 groups before
      phacoemulsification based on the type of ophthalmic viscosurgical device (OVD)
      used during surgery: Viscoat and Hyal-2000 (soft-shell technique), Viscoat alone,
      Hyal-2000 alone, or Provisc (sodium hyaluronate 1%) alone. All patients were
      operated on using the same technique except for the OVD. The visual acuity,
      corneal endothelial cell density, corneal thickness, and intraocular pressure
      (IOP) were evaluated postoperatively. RESULTS: The rate of endothelial cell loss
      2 months after surgery in eyes with a nuclear opacity grade of > or =4 was
      significantly different between the 4 OVD groups. The rate in eyes with a nuclear
      opacity grade of < or =3 was not significantly different between the groups.
      There were no statistically significant differences between the 4 groups in
      visual acuity, corneal thickness, or IOP throughout the follow-up period.
      CONCLUSION: The soft-shell technique using Viscoat and Hyal-2000 protected
      corneal endothelial cells during cataract surgery in patients with a nuclear
      opacity grade of > or =4.

PMID- 15519091
TI  - Cataract surgery in sympathetic ophthalmia.
AB  - PURPOSE: To analyze the results of cataract surgery in patients with sympathetic
      ophthalmia. SETTING: Sankara Nethralaya, Medical Research Foundation, Chennai,
      India. METHODS: This study comprised 66 patients (132 eyes) with sympathetic
      ophthalmia seen at the uveitis referral clinic between January 1990 and July
      2001; 42 eyes (31.8%) had cataract. Cataract surgery was performed in 17
      sympathizing eyes and 1 exciting eye (17 patients). The records of these 18 eyes
      were retrospectively analyzed. Three eyes had extracapsular cataract extraction
      (ECCE) with intraocular lens (IOL) implantation, 6 eyes had ECCE without IOL
      implantation, and 9 eyes had phacoemulsification with IOL implantation. The mean
      follow-up was 28.7 months (range 3 to 60 months). RESULTS: The causes of
      sympathetic ophthalmia were penetrating trauma (n = 8 eyes), ocular surgery (n =
      6), perforated corneal ulcer (n = 2), and cyclocryotherapy (n = 1). The most
      common cataract type, present in 7 eyes (38.8%), was mixed (posterior subcapsular
      and posterior polar). Visual acuity improved after surgery in 13 eyes (72.2%).
      The main factors impairing visual recovery were submacular scar and optic
      atrophy, which were sequelae of the sympathetic ophthalmia. Posterior capsule
      opacification was noted in 14 eyes (77.7%); it was visually significant in 6
      eyes. There was no significant difference in postoperative inflammation or
      disease reactivation between the 3 types of surgery. CONCLUSIONS: Cataract
      extraction in cases of sympathetic ophthalmia can be safely and successfully
      performed with vigilant preoperative and postoperative control of inflammation,
      careful surgical planning, and meticulous surgical technique. The final visual
      outcome, however, depends on the posterior segment complications of the disease.

PMID- 15519092
TI  - Normal values for a clinical test of letter-recognition contrast thresholds.
AB  - PURPOSE: To investigate the contrast thresholds (CTs) in normal subjects using a
      high-luminance, letter-recognition task under clinically relevant testing
      conditions. SETTING: Texas Tech University Health Sciences System, Lubbock,
      Texas, USA. METHODS: Sixty normal subjects aged 20 to 49 years with a best
      corrected visual acuity of 20/20 or better in both eyes participated. M & S
      Technologies software was used to display black-on-white Sloan letters at
      contrast levels of 25%, 20%, 15%, 12%, and 10% through 1% in 1% decrements. The
      effects of age, sex, optotype size, eye dominance, ambient illumination level
      (bright = 625 - 630 lux; dim = <3 lux), and direction of approach to threshold
      were analyzed using a multivariate, ordinary, least-squares analysis. RESULTS:
      Age and sex did not influence CTs. Ascending versus descending testing was not
      statistically significant (P>.5). The effects of room illumination and eye
      dominance were significant (P<.01). Significant differences were found between
      20/30 and 20/50, 20/30 and 20/70, and 20/50 and 20/70 optotype sizes (P<.01 for
      all comparisons). CONCLUSIONS: A commercially available, computer-based test of
      CTs was easy to administer and apparently easy for inexperienced subjects to
      perform. The results suggest criteria for detecting visual problems concerned
      with familiar but complex spatial-image shapes. This information might be used to
      assess the effects of treatments such as laser refractive surgery on recognition
      contrast. Further study is warranted.

PMID- 15519093
TI  - Combined ICRS insertion and LASIK to maximize postoperative residual bed
      thickness in high myopia.
AB  - PURPOSE: To describe a new technique and early outcomes of combined intrastromal
      corneal ring segment (ICRS) insertion and laser in situ keratomileusis (LASIK) to
      treat patients with moderate to high myopia and thin corneas. SETTING: University
      based academic practice, Boston, Massachusetts, USA. METHODS: Combined ICRS
      insertion and LASIK was performed in 2 stages: ICRS channel formation (stage I)
      followed by LASIK and ICRS insertion (stage II). RESULTS: Fifteen eyes of 11
      patients with a mean preoperative spherical equivalent of -9.98 diopters (D) +/-
      2.60 (SD) (range -7.13 to -16.25 D) and mean preoperative astigmatism of 1.11 +/-
      0.75 D (range 0.00 to -3.00 D) were treated with combined ICRS insertion and
      LASIK. The mean central pachymetry was 526.13 +/- 35.69 microm (472 to 579
      microm). The uncorrected visual acuity was 20/40 or better in 7 of 15 eyes
      (46.67%) at 1 month, 6 of 12 eyes (50.00%) at 3 months, 5 of 12 eyes (41.67%) at
      6 months, and 6 of 12 eyes (50.00%) at 12 months. The best spectacle-corrected
      visual acuity was 20/40 or better at all times. Postoperative maps confirmed the
      absence of ectasia. The postoperative spherical equivalent was within +/-1.00 D
      of the intended refraction in 11 of 15 eyes (73.33%) at 1 month, 9 of 12 eyes at
      3 and 6 months, and 8 of 12 eyes (66.67%) at 12 months. CONCLUSIONS: Results of
      combined ICRS insertion and LASIK in moderately to highly myopic patients with
      relatively thin corneas were good. Long-term studies are needed to determine
      whether this procedure will decrease the risk of LASIK-induced keratectasia in
      these patients.

PMID- 15519094
TI  - Refractive changes after phacoemulsification combined with deep sclerectomy
      assisted by corneal topography.
AB  - PURPOSE: To evaluate the corneal surgically induced refractive change (SIRC)
      after phacoemulsification and deep sclerectomy. SETTING: Glaucoma Unit,
      Department of Ophthalmology, Hospital Ramon y Cajal, Madrid, Spain. METHODS: This
      prospective study comprised 38 eyes of 35 patients with a mean age of 77 years
      having phacoemulsification using a right clear corneal approach (temporal
      approach and nasal approach in the right eye and the left eye, respectively)
      combined with a deep sclerectomy and placement of a reticulated hyaluronic acid
      implant in the superior quadrant. Computerized keratography was performed
      preoperatively and 1 month and 3 months postoperatively. The SIRC was calculated
      at each follow-up by the Holladay-Cravy-Koch method and was expressed vectorially
      in 3 Cartesian coordinates to facilitate statistical analysis. RESULTS: The
      magnitude of the resulting mean SIRC components was very small. No significant
      change was observed in any vectorial component 1 month and 3 months
      postoperatively. Overall, 47.4% of patients had an induced with-the-rule
      astigmatism change at 3 months (range 0.03 to 1.67 diopters [D]); however, the
      mean change was less than 0.50 D and not statistically significant. The mean
      spherical postoperative change was greater in left eyes than in right eyes (P =
      .05). No statistically significant changes between the right eye and left eye
      were observed in the astigmatism vectorial components. CONCLUSIONS: Overall, the
      refractive change after phacoemulsification combined with deep sclerectomy was
      mild and not clinically significant. The greater mean spherical change in left
      eyes than in right eyes might be related to the phacoemulsification approach.

PMID- 15519095
TI  - Comparison of the biomechanical behavior of foldable intraocular lenses.
AB  - PURPOSE: To compare a standardized battery of biomechanical laboratory tests to
      assess the performance of popular foldable intraocular lenses (IOLs). SETTING:
      Biomedical testing facilities, Alcon Research, Ltd., Fort Worth, Texas, USA.
      METHODS: Using industry-standard biomechanical testing techniques, 1- and 3-piece
      foldable IOLs (Alcon AcrySof MA60BM, MA30BA, SA30AL, SA60AT; Allergan Sensar
      AR40, PhacoFlex II SI-40NB; Bausch & Lomb Soflex LI61U; Pharmacia & Upjohn CeeOn
      920) and a 1-piece all-poly(methyl methacrylate) (PMMA) IOL (Alcon MZ30BD) were
      tested under identical conditions with regard to (1) tensile/elastic properties
      by comparing haptic pull strength and haptic elongation and (2) compression
      properties by comparing haptic compression forces, haptic compression force decay
      over time, and axial displacement. All tests were performed with the IOLs
      submersed in a controlled-temperature water bath (mean 35 degrees C +/- 2 degrees
      C [SD]). RESULTS: For all IOLs, the ultimate elongation and pull strength of the
      haptics before failure was highest with the Alcon SA30AL and SA60AT. Similarly,
      the force required to compress haptics to a prescribed 10.0 mm diameter was least
      with the SA30AL and the SA60AT lenses. These 1-piece lenses also showed the least
      decay of residual compression force as a function of time. Optic displacement
      along the optical axis with haptic compression to 10.0 mm was least with the
      Alcon 1-piece IOLs and the all-PMMA control IOL. CONCLUSION: AcrySof 1-piece
      SA30AL and SA60AT IOLs demonstrated superior biomechanical characteristics over
      other foldable IOL designs.

PMID- 15519096
TI  - Posterior capsule opacification in rabbit eyes implanted with hydrophilic acrylic
      intraocular lenses with enhanced square edge.
AB  - PURPOSE: To evaluate the development of posterior capsule opacification (PCO)
      after implantation of single-piece hydrophilic acrylic intraocular lenses (IOLs)
      with an enhanced square edge. SETTING: John A. Moran Eye Center, University of
      Utah, Salt Lake City, Utah, USA. METHODS: The standard 570H Centerflex (Rayner
      Ltd.) design was compared to 2 new designs with enhanced square edges: the 570E
      and the 570C. Ten IOLs of each type were implanted in a randomized manner by the
      same surgeon in 15 pigmented rabbits. After a follow-up of 3 weeks, the rabbits
      were killed and the eyes were analyzed from the posterior view. The intensity of
      central PCO, peripheral PCO, and Soemmering's ring formation was graded from 0 to
      4. The area of Soemmering's ring was graded from 0 to 4 based on the number of
      quadrants involved. Other parameters analyzed were capsulorhexis coverage of the
      IOL edge and IOL centration and fixation. Results from the posterior view were
      complemented by histopathological evaluation. RESULTS: Posterior capsule
      opacification was lowest in the 570C group, highest in the 570H group, and
      intermediate in the 570E group. There was a statistically significant difference
      between the 3 groups in peripheral PCO (P = .039). No significant difference was
      found between the groups in the other parameters analyzed. When cell ingrowth
      occurred with the 570H, it started at the optic-haptic junctions, as observed
      during the clinical follow-up and confirmed by gross and histopathological
      analyses. CONCLUSIONS: The square optic edge is the most important IOL design
      feature for PCO prevention. However, it should be present for 360 degrees around
      the IOL optic to provide an effective barrier effect.

PMID- 15519097
TI  - Removal times for a dispersive and a cohesive ophthalmic viscosurgical device
      correlated with intraocular lens material.
AB  - PURPOSE: To investigate the removal times of ophthalmic viscosurgical devices
      (OVDs) with different intraocular lens (IOL) designs and materials. SETTING:
      Center for Research on Ocular Therapeutics and Biodevices, Department of
      Ophthalmology, Storm Eye Institute, Medical University of South Carolina,
      Charleston, South Carolina, USA, and Heidelberg IOL & Refractive Surgery Research
      Group, Department of Ophthalmology, Ruprecht-Karls-University of Heidelberg,
      Heidelberg, Germany. METHODS: In a standardized laboratory setup, the Miyake
      Apple posterior view video technique was used to evaluate OVD removal from
      capsular bags in human autopsy eyes implanted with poly(methyl methacrylate)
      (PMMA), silicone, and acrylic IOLs. The cohesive OVD ProVisc (sodium hyaluronate
      1.0%) and the dispersive OVD Viscoat (sodium hyaluronate 3.0% and chondroitin
      sulfate 4.0%) were stained with fluorescein for better visualization. The open
      sky preparation and an Alcon Series 20000 Legacy phaco machine with a flow rate
      of 25 mL/min and a vacuum setting of +500 mm Hg (maximum irrigation/aspiration)
      were used. The time needed for complete removal of the cohesive and dispersive
      OVDs with each IOL type was measured and analyzed statistically. RESULTS: The
      mean removal times for both OVDs were as follows: Alcon MZ60BD PMMA IOL-25.0
      seconds +/- 3.7 (SD) (Viscoat), 15.9 +/- 6.9 seconds (ProVisc); Alcon AcrySof
      MA60BM IOL-35.5 +/- 10.0 seconds (Viscoat), 25.6 +/- 4.7 seconds (ProVisc);
      Chiron/Bausch & Lomb C1043 silicone IOL-46.5 +/- 10.5 seconds (Viscoat), 17.3 +/-
      2.1 seconds (ProVisc); AMO SI-30 silicone IOL-33.5 +/- 3.1 seconds (Viscoat),
      15.3 +/- 6.3 seconds (ProVisc); and Pharmacia 912 silicone IOL-18.3 +/- 5.8
      seconds (Viscoat), 19.8 +/- 4.3 seconds (ProVisc). CONCLUSIONS: Differences in
      OVD removal times were detected. The removal time for the cohesive OVD correlated
      with the IOL material. Overall, the time needed for complete removal was
      significantly longer for the dispersive OVD than for the cohesive OVD.

PMID- 15519098
TI  - Evaluation of cut quality using the Amadeus microkeratome with different
      settings.
AB  - PURPOSE: To evaluate the quality of keratectomy specimens created with the
      Amadeus microkeratome (AMO) using scanning electron microscopy (SEM). SETTING:
      Johannes Gutenberg-University Hospital, Department of Ophthalmology, Mainz, and
      the Department of Anatomy, Justus Liebig-University, Giessen, Germany. METHODS:
      Corneal cuts were performed in freshly enucleated pig eyes using the Amadeus
      microkeratome with 9 combinations of oscillation rate and head-advance speed. For
      the cutting trials, oscillation rates of 8000, 13,000, and 18,000 rpm and head
      advance speeds of 1.0, 2.5, and 4.0 mm/s were chosen. Fifty-four eyes were
      included, resulting in 9 groups of 6 eyes for each configuration. The surfaces
      and edges of the flaps were examined using SEM. RESULTS: At fixed oscillation
      rates, an increase in head-advance speed led to lower quality cuts, higher
      surface roughness, and irregular cut edges. At fixed head-advance speeds, an
      increase in oscillation rates improved the cut quality, resulting in smoother
      surface characteristics. CONCLUSIONS: Smooth and regular surfaces and cut edges
      can be achieved by choosing high oscillation rates and low head-advance speeds.
      Microkeratomes that enable the user to adjust the oscillation rate and head
      advance speed can be used to maximize surface smoothness and improve customized
      refractive surgery.

PMID- 15519099
TI  - Photochemical keratodesmos as an adjunct to sutures for bonding penetrating
      keratoplasty corneal incisions.
AB  - PURPOSE: To evaluate the benefit of photochemical keratodesmos (PKD) in acute
      wound closure of penetrating keratoplasty (PKP) corneal incisions in vivo.
      SETTING: Massachusetts General Hospital and Massachusetts Eye and Ear Infirmary,
      Boston, Massachusetts, USA. METHODS: Penetrating keratoplasty incisions were
      performed in both eyes of 6 New Zealand white rabbits, followed by application of
      1.5 mM rose bengal dye at the wound edges. The incision in 1 eye of each rabbit
      was irradiated with neodymium:YAG laser light at 532 nm and fluence of 40 J/cm2;
      the contralateral control eye was untreated. Intraocular pressure at which fluid
      leaked at the edges (IOPL) was determined immediately after surgery. RESULTS: The
      mean IOPL was 410 mm Hg +/- 70 (SD) in the PKD-treated eyes and 250 +/- 150 mm Hg
      in the unirradiated eyes. The difference was statistically significant by paired
      t test (P<.05). CONCLUSIONS: Photochemical keratodesmos may be a useful adjunct
      to sutures for approximating PKP corneal incisions in the immediate postoperative
      period. This process does not induce high temperature, and thus denaturation can
      be avoided and structural integrity restored.

PMID- 15519100
TI  - Beyond the P: III: Possible insignificance of the nonsignificant P value.

PMID- 15519101
TI  - Ferrara intracorneal ring implantation and cataract surgery for the correction of
      pellucid marginal corneal degeneration.
AB  - We report a case of Ferrara intracorneal ring (Mediphacos) implantation and
      cataract surgery for the correction of pellucid marginal corneal degeneration.
      Preoperatively, the patient's uncorrected visual acuity (UCVA) was 0.05 in the
      right eye and 0.10 in the left eye. The best spectacle-corrected visual acuity
      (BSCVA) was 0.50 with -2.00 -11.25 x 80 in the right eye and 0.60 with -2.00 
      5.50 x 95 in the left eye. One month postoperatively, the UCVA was 0.50 in the
      right eye and 0.30 in the left eye. The BSCVA was 0.80 with -1.00 in the right
      eye and 0.60 with -0.75 -1.25 x 160 in the left eye. Ferrara intrastromal rings
      and cataract surgery resulted in a more regular corneal shape with a reduction in
      astigmatism for good visual recovery.

PMID- 15519102
TI  - Ten-year follow-up of a ciliary sulcus-fixated silicone phakic posterior chamber
      intraocular lens.
AB  - In 1992, a ciliary sulcus-fixated, silicone, phakic posterior chamber intraocular
      lens (PPC IOL) (Adatomed, Fyodorov type) was implanted in both eyes of a 42-year
      old white woman to correct high myopia (right eye, -17.0 diopters [D]; left eye, 
      11.5 D). In the right eye, localized cortical opacification was present in the
      anterior part of the natural lens preoperatively but did not progress during a 10
      year follow-up period. With Scheimpflug photography, it was possible to detect a
      space between the natural lens and the IOL that was not evident on slitlamp
      examination. Maintenance of space between an IOL and the natural lens appears to
      be an important factor in preventing cataract formation after PPC IOL
      implantation.

PMID- 15519103
TI  - Sudden visual loss after uneventful cataract surgery: Snuff syndrome.
AB  - We describe a case in which the patient had routine, uneventful cataract surgery
      and developed snuff syndrome on day 1 postoperatively. The patient had
      pseudoexfoliation syndrome and normal intraocular pressure that was well
      controlled by timolol and previous laser trabeculoplasty. Although the visual
      result had been good after surgery in the first (right) eye with a best corrected
      visual acuity (BCVA) of 6/5, this adverse event, which decreased the BCVA in the
      left eye from 6/24 preoperatively to hand movements postoperatively, was
      unexpected. Systemic evaluation failed to identify a specific cause. Data were
      collected prospectively on 1000 subsequent, consecutive cases of cataract
      surgery, but we were unable to find pathogenetic data on this occurrence.

PMID- 15519104
TI  - Lenticular myopia from oil-drop cataract: a cautionary note in laser in situ
      keratomileusis.
AB  - We present 5 patients with oil-drop cataracts in whom the underlying lenticular
      cause of myopic regression after laser in situ keratomileusis (LASIK) had been
      missed by their ophthalmologists. As a result, the patients were scheduled for or
      had had LASIK enhancement before presentation to us. After oil-drop cataracts
      were diagnosed, phacoemulsification was performed successfully in at least 1 eye
      of all patients. These cases underscore the importance of considering lens
      induced myopia in refractive surgery patients, especially those with an unstable
      preoperative refraction or postoperative myopic regression. Refractive surgery in
      these cases can unnecessarily complicate the measurement of intraocular lens
      strength in cataract surgery.

PMID- 15519105
TI  - Postoperative Corynebacterium macginleyi endophthalmitis.
AB  - A 72-year-old man with chronic endophthalmitis who received steroid treatment for
      3 months came to our center. Sterile endophthalmitis after cataract extraction
      had been diagnosed. Aqueous samples including smears, classic cultures, and
      polymerase chain reaction were taken for microbiological study. Amplified DNA was
      sequenced to identify the pathogen. Polymerase chain reaction amplification was
      positive for bacteria. Sequence analysis showed Corynebacterium macginleyi as the
      causal agent in 48 hours. The culture and smear stains from the ocular samples
      were negative. The patient was successfully treated with vancomycin. Polymerase
      chain reaction and subsequent DNA-typing were useful in detecting the
      microorganisms that caused the chronic endophthalmitis.

PMID- 15519106
TI  - Acute angle-closure glaucoma caused by vitreous prolapse after neodymium:YAG
      posterior capsulotomy.
AB  - We report the second known case of acute angle-closure glaucoma from vitreous
      prolapse after neodymium:YAG (Nd:YAG) laser posterior capsulotomy in a patient
      with a posterior chamber intraocular lens (IOL). This is the first reported case
      to result in corneal decompensation that required penetrating keratoplasty. The
      rare complication of vitreous prolapse was unusual in this patient because of the
      presence of a posterior chamber IOL, a small 4.0 mm capsulotomy opening, and low
      (26 mJ) Nd:YAG laser energy.

PMID- 15519107
TI  - Assessment of capsular block syndrome with anterior segment optical coherence
      tomography.
AB  - A 59-year-old woman developed progressive, moderate myopia 1 year after routine
      phacoemulsification and insertion of a soft posterior chamber intraocular lens
      (IOL). After biomicroscopy, late capsular block was diagnosed and treated with a
      neodymium:YAG laser posterior capsulotomy. The myopia disappeared immediately.
      This case was illustrated using optical coherence tomography developed for the
      anterior segment. After capsulotomy, the IOL moved backward by 448 microm,
      corresponding to -0.75 diopter of induced myopia.

PMID- 15519108
TI  - Topical anesthesia for cataract surgery in highly myopic eyes.

PMID- 15519109
TI  - Sliding scale of IOL power for sulcus fixation using computer simulation.

PMID- 15519110
TI  - Mini-nuc technique in phacoemulsification.

PMID- 15519111
TI  - Measuring gross motor recovery in young children with early brain injury.
AB  - Motor outcome measures may be used in both research and clinical practice.
      Although many motor outcome measures exist, only a small subset are suitable for
      use in children, and an even smaller subset is suitable for use in children under
      the age of 5 years who are undergoing rapid motor development. In this article,
      the issues involved in choosing an outcome measure are reviewed, and four of the
      most common gross motor outcomes measures used in young children are discussed.

PMID- 15519113
TI  - Value of biochemical markers for outcome in term infants with asphyxia.
AB  - The aim of this study was to define the predictive values of serum and
      cerebrospinal fluid concentrations of interleukin-6 and neuron-specific enolase
      and urinary uric acid/creatinine ratio for outcome in term infants with perinatal
      asphyxia. All biochemical markers were measured simultaneously within the 24-72
      hours of life in 21 infants. The infants were monitored with a standardized
      neurologic and developmental evaluation protocol over the 2 years of life. The
      overall outcome at 2 years of age was categorized as "favorable" or "adverse".
      According to Sarnat and Sarnat classification, 12 infants had mild encephalopathy
      and 9 infants had moderate to severe encephalopathy. Seven of 9 (78%) infants
      with moderate to severe encephalopathy had adverse outcome. However, all infants
      with mild encephalopathy had favorable outcome. Interleukin-6 and neuron specific
      enolase levels in cerebrospinal fluid and serum interleukin-6 levels were
      significantly correlated with the degree of encephalopathy, as well as the
      outcome. Interleukin-6 in cerebrospinal fluid (cutoff value, 25.9 pg/mL) had the
      highest predictive value among the biochemical markers. The predictive factors
      identified in this study should be examined for their ability in a fresh clinical
      sample in the neonatal intensive care unit before these markers can be applied to
      the routine clinical of infants with perinatal asphyxia.

PMID- 15519112
TI  - Volumetric analysis of regional cerebral development in preterm children.
AB  - Preterm birth is frequently associated with both neuropathologic and cognitive
      sequelae. This study examined cortical lobe, subcortical, and lateral ventricle
      development in association with perinatal variables and cognitive outcome. High
      resolution volumetric magnetic resonance imaging scans were acquired and
      quantified using advanced image processing techniques. Seventy-three preterm and
      33 term control children ages 7.3-11.4 years were included in the study. Results
      indicated disproportionately enlarged parietal and frontal gray matter, occipital
      horn, and ventricular body, as well as reduced temporal and subcortical gray
      volumes in preterm children compared with control subjects. Birth weight was
      negatively correlated with parietal and frontal gray, as well as occipital horn
      volumes. Intraventricular hemorrhage was associated with reduced subcortical gray
      matter. Ventricular cerebrospinal fluid was negatively correlated with
      subcortical gray matter volumes but not with white matter volumes. Maternal
      education was the strongest predictor of cognitive function in the preterm group.
      Preterm birth appears to be associated with disorganized cortical development,
      possibly involving disrupted synaptic pruning and neural migration. Lower birth
      weight and the presence of intraventricular hemorrhage may increase the risk for
      neuroanatomic abnormality.

PMID- 15519114
TI  - Pediatric physical functioning reference curves.
AB  - We developed normative profiles of physical functioning (mobility and self-care)
      in infancy up through 14 years of age with an expanded version of the Pediatric
      Evaluation of Disability Inventory. Mobility and self-care reference curves were
      based on the original Pediatric Evaluation of Disability Inventory
      standardization data (n = 412) and data from an additional cross-sectional,
      convenience sample (n = 373) via web-based survey, telephone or in-person
      interviews of parents. This new sample, which included children up through 14
      years-of-age, was stratified for race, age, and sex, but was primarily limited
      geographically to the Northeast region of the United States. Goodness of fit of
      male, female, and combined sex (male and female) reference curves was examined.
      The mobility and self-care reference curves produced efficient and well-fitting
      estimates of conventional percentiles (3rd, 10th, 25th, 50th, 75th, 97th).
      Differences between males' and females' reference curves were negligible. This
      study highlights the use of these reference curves for determining the functional
      impact of Pompe disease, a lysosomal storage disorder that affects skeletal and
      cardiac muscle, restricting normal expression of mobility and self-care
      activities. This physical functioning instrument could also be used to evaluate
      the impact of muscle weakness in other neuromuscular disorders.

PMID- 15519115
TI  - Do serum sodium levels predict febrile seizure recurrence within 24 hours?
AB  - The American Academy of Pediatrics Practice Parameter, The Neurodiagnostic
      Evaluation of a Child with a First Simple Febrile Seizure, does not recommend
      serum electrolytes be obtained routinely. Two reports from Europe, however,
      identified relative hyponatremia as a risk factor for febrile seizure recurrence
      within 24 hours. If confirmed, this would have potential impact on the approach
      to these patients. The charts of 175 sequential children ages 6 months to 5 years
      who presented to the Children's Hospital of Buffalo emergency room in 1999 with
      generalized seizures lasting less than 15 minutes were retrospectively reviewed.
      One hundred thirty-six patients were febrile and 39 (control group) were
      afebrile. Serum electrolytes were performed on all. The mean serum sodium for the
      27 children with more than 1 febrile seizure in 24 hours (135.48 mmol/L) did not
      differ from those 109 febrile children whose seizures did not recur within 24
      hours (135.56 mmol/L). Of interest, the mean serum sodium for the 109 children
      with simple febrile seizures, as well as those with recurrent "simple" febrile
      seizures were significantly lower than the control group of children with
      afebrile seizures. These findings reaffirm the recommendation of the American
      Academy of Pediatrics Practice Parameter to not routinely obtain electrolytes.

PMID- 15519116
TI  - Dopamine D4 receptor gene and attention deficit hyperactivity disorder.
AB  - Attention deficit hyperactivity disorder is a prevalent disorder characterized by
      hyperactivity, impulsivity, and attentional dysfunction. It is familial and
      heritable. Its pathophysiology is thought to involve an abnormality of the
      brain's dopaminergic neurotransmitter system. Recent work has identified a
      distinct polymorphism of the dopamine D4 receptor gene in normal people with a
      behavioral temperament profile characterized by features of "novelty seeking"
      which include impulsive and exploratory behaviors. These personality traits are
      also characteristic of children with attention deficit hyperactivity disorder,
      especially the hyperactive-impulsive type. This study investigated the
      relationship between dopamine D4 receptor gene polymorphism, temperament
      categories, and attention deficit hyperactivity disorder in 81 children with the
      disorder and 24 control subjects. There was no significant association between
      dopamine D4 receptor gene alleles, Novelty Seeking traits, and the Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition diagnosis of attention
      deficit hyperactivity disorder--Hyperactive impulsive type or Inattentive type.

PMID- 15519117
TI  - Topiramate slow dose titration: improved efficacy and tolerability.
AB  - Topiramate is an effective treatment for several types of seizures. The aim of
      this study is to assess the efficacy and tolerability of slow topiramate dose
      titration as add-on therapy in childhood epilepsy. This investigation is a
      prospective open-label, single-center, add-on study in 22 children with a
      diagnosis of refractory epilepsy. Topiramate (dose 0.5-2 mg/kg/day) was titrated
      at 2-week intervals up to the recommended dose of 6-12 mg/kg/day. Seizure
      frequency rate reduction was significant, declining from 23 +/- 5.1 seizures/week
      (mean +/- S.E.M.) at baseline phase to 3.5 +/- 1.2 seizures/week at the end of
      the 16-week stabilization phase (P < 0.001). After 16 weeks of stabilization, 19
      patients (86%) had more than 50% seizure reduction. Seven patients (31%) were
      100% seizure-free. Two patients (9%) manifested no improvement; only one patient
      (5%) did not tolerate the added drug and discontinued topiramate. One patient
      manifested severe side effects, whereas 21 patients experienced mild to moderate
      side effects mostly represented by somnolence, nervousness, and anorexia with or
      without weight loss. We conclude that slow dose titration improves efficacy and
      tolerability of topiramate as add-on therapy in the treatment in refractory
      epilepsy.

PMID- 15519118
TI  - Leptomeningeal angiomatosis with infantile spasms.
AB  - We describe a 7-month-old female with leptomeningeal angiomatosis who developed
      infantile spasms. She did not manifest facial nevus or ocular choroidal angioma.
      Leptomeningeal angiomatosis is characterized by venous angiomas of leptomeninges
      and usually accompanied by facial nevus, a condition known as Sturge-Weber
      syndrome. In Sturge-Weber syndrome, leptomeningeal angiomas can cause infantile
      spasms but much less frequently than in other neurocutaneous syndromes, such as
      tuberous sclerosis. This patient is the first reported case of leptomeningeal
      angiomatosis without facial nevus who developed infantile spasms. Leptomeningeal
      angiomas should be taken into consideration as a cause of infantile spasms, even
      in the absence of facial nevus. We suggest that this case is clinically within
      the spectrum of Sturge-Weber syndrome, and that the embryologic origin of this
      case is similar to that of Sturge-Weber syndrome.

PMID- 15519119
TI  - Kinesigenic attacks with ictal electroencephalographic abnormalities.
AB  - We report on a 14-year 5-month-old male who had attacks similar to those of
      paroxysmal kinesigenic choreoathetosis. The attacks were elicited exclusively by
      sudden movements. On several occasions, these attacks were immediately followed
      by loss of consciousness or a seizure. Ictal electroencephalograms of his attacks
      without loss of consciousness or a seizure indicated 1.5-3.0 Hz activity in the
      left hemisphere. A small dosage of carbamazepine was remarkably effective in
      stopping the attacks. This case demonstrates that a thorough ictal
      electroencephalographic examination is indispensable for clarifying the
      pathophysiology of kinesigenic attacks. The relationship between paroxysmal
      kinesigenic choreoathetosis and supplementary motor area seizures is also
      discussed.

PMID- 15519120
TI  - Development of tuberculoma during therapy presenting as hemianopsia.
AB  - A 6-year-old, previously healthy male presented with fever and lethargy.
      Tuberculous meningitis was suspected after cerebrospinal fluid examination.
      Antituberculous drugs were administered, and an initial computed tomographic scan
      of brain revealed mild ventriculomegaly only. Steroids were instituted on day 16
      and gradually withdrawn 1 month later. Nine weeks after the initiation of
      antituberculous therapy, markedly impaired visual acuity and bitemporal
      hemianopsia were observed. Magnetic resonance imaging of brain revealed multiple
      tuberculomas, including involvement of the optic chiasm. Hydrocephalus was
      present. A ventriculoperitoneal shunt was inserted, and steroids were
      reinstituted. Visual acuity improved 9 weeks after the onset of visual acuity
      impairment and returned to normal 24 weeks later.Follow-up computed tomographic
      scan of brain 1 year later demonstrated complete resolution of tuberculomas.
      Development of intracranial tuberculoma during antituberculous therapy, although
      rare, dose not represent treatment failure, and continuation of antituberculous
      drugs, with or without the addition of steroids, will usually resolve the
      lesions.

PMID- 15519121
TI  - Noonan syndrome, moyamoya-like vascular changes, and antiphospholipid syndrome.
AB  - This reports describes a 12-year-old Japanese female with Noonan syndrome who had
      antiphospholipid syndrome and moyamoya-like vascular changes. She presented
      choreic movements in her face and extremities. She manifested phenotypic features
      of Noonan syndrome with short stature, mental retardation, and a webbed neck.
      Magnetic resonance angiography revealed occlusion of bilateral internal carotid
      arteries and moyamoya-like vascular changes around the basal ganglion region.
      Pimozide completely resolved the patient's choreic movements. Tests for
      anticardiolipin antibody and lupus anticoagulant were positive. The patient has
      manifested no symptoms for 2 years with pimozide, aspirin, and growth hormone
      treatment, without further aggravation of moyamoya-like vascular changes. This
      article is the first report of Noonan syndrome with antiphospholipid syndrome and
      moyamoya-like vascular lesions.

PMID- 15519122
TI  - Hypersomnia and low cerebrospinal fluid hypocretin levels in acute disseminated
      encephalomyelitis.
AB  - A 7-year-old Japanese female diagnosed as having acute disseminated
      encephalomyelitis presented seizures, visual symptoms, and hypersomnia with
      bilateral lesions in the white matter, basal ganglia, and hypothalamus. Her
      clinical findings and demonstrated lesions in neuroimages were similar to those
      of Von Economo's encephalitis lethargica. Her hypocretin, the hypothalamic
      neuropeptide controlling sleep-awake cycle, was significantly low in the
      cerebrospinal fluid (146 pg/mL) on admission. Successive measures resulted in the
      gradual recovery of cerebrospinal fluid hypocretin to the normal range (263
      pg/mL) as her excessive daytime sleepiness was reduced. Decreased hypothalamic
      hypocretin neurotransmission may be involved in this symptomatic case of
      hypersomnia associated with acute disseminated encephalomyelitis.

PMID- 15519123
TI  - A case of X-linked agammaglobulinemia with progressive encephalitis.
AB  - This report describes a case of agammaglobulinemia with progressive encephalitis.
      The patient was a 6-year-old male who was diagnosed as having Bruton-type
      agammaglobulinemia at age 6 months. After the diagnosis was made, he received
      monthly intravenous immunoglobulin replacement with a residual immunoglobulin G
      level of more than 400 mg/dL. At 5 years of age, he presented with symptoms of
      mental deterioration and gait disturbance. He had no history of infection of the
      central nervous system. Brain biopsy revealed CD8-positive T-cell infiltration
      with cortical damage, but no infectious agents were observed by either
      immunohistochemistry or virus isolation. Treatment with subcutaneous interferon
      alpha and high-dose intravenous immunoglobulin was begun, and clinical symptoms
      improved within a month. Hence, patients with agammaglobulinemia should be
      carefully monitored for complications of the central nervous system even if there
      is no history of infection.

PMID- 15519124
TI  - Paralytic ileus in MELAS with phenotypic features of MNGIE.
AB  - This report describes a child having the syndrome of overlapping phenotypic
      features of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke
      like episodes (MELAS) and mitochondrial neurogastrointestinal encephalopathy
      syndrome (MNGIE). Mitochondrial DNA analysis revealed a point mutation at
      position A3243G, whereas activity of thymidine phosphorylase and its
      corresponding gene analysis were normal. The most striking feature of this case
      was paralysis of one segment of the terminal ileum observed on laparotomy. The
      electron microscopic findings of the resected ileum and colon by limited right
      hemicolectomy disclosed accumulation of numerous enlarged mitochondria with ill
      defined cristae which were similar to mitochondria reported in three previous
      MELAS cases and one MNGIE case with intestinal dysmotility. We emphasize that the
      MELAS and MNGIE phenotypes overlapped in this case and that the mechanism of
      acute ileus in MELAS was associated with functional paralysis of the intestine.

PMID- 15519126
TI  - Temporo-occipital spikes: are they so typical for Kabuki syndrome?

PMID- 15519128
TI  - c-Fos immunohistochemical mapping of the audiogenic seizure network and tonotopic
      neuronal hyperexcitability in the inferior colliculus of the Frings mouse.
AB  - The Frings mouse is a model of audiogenic seizure (AGS) susceptibility. The
      genetic locus responsible for the AGS phenotype in the Frings mouse has been
      named monogenic audiogenic seizure-susceptible (MASS1). MASS1 is unique in that
      it is one of only two identified seizure loci that are not associated with an ion
      channel mutation. Furthermore, Frings mice display a robust AGS phenotype
      demonstrating very high and prolonged susceptibility to sound-induced tonic
      extension seizures. The purpose of this investigation was to use c-Fos
      immunohistochemistry to map the brain structures involved in the Frings AGS and
      to examine neuronal hyperexcitability in the inferior colliculus, the brain
      structure that is recognized as the site of AGS initiation. AGS mapping revealed
      that intense seizure-induced neuronal activation was mostly limited to structures
      involved in a brainstem seizure network, including the external and dorsal nuclei
      of the inferior colliculus, as observed in other AGS rodents. Acoustically
      induced c-Fos expression in the central nucleus of the inferior colliculus to sub
      AGS threshold tone stimulations displayed a greater level of neuronal activation
      in AGS-susceptible Frings, DBA/2J and noise-primed C57BL/6J mice compared to AGS
      resistant C57BL/6J and CF1 mice. The AGS-susceptible mice also displayed c-Fos
      immunoreactivity that was more focused within the tonotopic response domain of
      the inferior colliculus compared to AGS-resistant mice. Furthermore, Frings mice
      displayed significantly greater tonotopic hyper-responsiveness compared to other
      AGS-susceptible mice.

PMID- 15519127
TI  - Carbamazepine pharmacokinetics are not affected by zonisamide: in vitro
      mechanistic study and in vivo clinical study in epileptic patients.
AB  - Carbamazepine is metabolized by CYP3A4 and several other cytochrome P450 enzymes.
      The potential effects of zonisamide on carbamazepine pharmacokinetics (PK) have
      not been well characterized, with contradictory literature reports. Hence, an in
      vitro study was designed to evaluate the cytochrome P450 inhibition spectrum of
      zonisamide using human liver microsomes. Further, an in vivo steady-state study
      was performed to measure the effect of zonisamide on carbamazepine PK in
      epileptic patients, and monitor zonisamide PK. In vitro human liver microsomes
      were incubated with zonisamide (200, 600 or 1000 microM) in the presence of
      appropriate probe substrates to assess selected cytochrome P450 activities. In
      vivo, the effect of zonisamide, up to 400 mg/day, on the steady-state PK of
      carbamazepine and carbamazepine-epoxide (CBZ-E) was studied in 18 epileptic
      patients. In vitro, zonisamide did not inhibit CYP1A2 and 2D6, and only weakly
      inhibited CYP2A6, 2C9, 2C19, and 2E1. The estimated Ki for zonisamide inhibition
      of CYP3A4 was 1076 microM, 12 times higher than typical unbound therapeutic serum
      zonisamide concentrations. In vivo, no statistically significant differences were
      observed for mean Cmax, Tmax, and AUC0-12 of total and free carbamazepine and CBZ
      E measured before and after zonisamide administration (300-400 mg/day for 14
      days). However, CBZ-E renal clearance was significantly (p < 0.05) reduced by
      zonisamide. The observed mean zonisamide t1/2 (36.3h), relative to approximately
      65 h reported in subjects on zonisamide monotherapy, reflects known CYP3A4
      induction by carbamazepine. Based on the lack of clinically relevant in vitro and
      in vivo effects, adjustment of carbamazepine dosing should not be required with
      concomitant zonisamide administration.

PMID- 15519129
TI  - Zonisamide and associated oligohidrosis and hyperthermia.
AB  - Zonisamide is an antiepileptic agent that is indicated as adjunctive therapy for
      the treatment of partial seizures in adults. Oligohidrosis has been reported in a
      small number of patients receiving zonisamide and, in a proportion of these
      patients, hyperthermia has occurred. Most reports of hyperthermia have been in
      children, typically occurring during the summer months. However, the mechanism of
      zonisamide-associated oligohidrosis is not fully understood. Thirteen events of
      oligohidrosis, or hyperthermia, associated with zonisamide were reported in the
      US during the 3 years after zonisamide was approved, an estimated incidence of 1
      case per 4590 patient-years. These events happened mostly in children. In Japan,
      all reported cases of zonisamide-associated oligohidrosis or hyperthermia have
      been in children, with an incidence of 1 case per 10,000 pediatric-years during
      the first 11 years of marketing. In each case, oligohidrosis was reversible upon
      discontinuation of zonisamide. Ensuring that children remain cool and well
      hydrated during hot weather can minimize the potential for hyperthermia resulting
      from oligohidrosis.

PMID- 15519130
TI  - The ketogenic diet does not alter brain expression of orexigenic neuropeptides.
AB  - Neuropeptide Y (NPY) and galanin are neuropeptides that are regulated by energy
      states and are also anticonvulsant. We tested the hypothesis that the
      anticonvulsant efficacy of the ketogenic diet (KD) is mediated by increased
      expression of NPY and galanin via alterations in food intake and energy
      metabolism. In situ hybridization revealed no effect of the KD on NPY or galanin
      mRNA expression, suggesting that increased expression of NPY and galanin do not
      contribute to the anticonvulsant effect of the KD.

PMID- 15519131
TI  - Levetiracetam influences human motor cortex excitability mainly by modulation of
      ion channel function--a TMS study.
AB  - PURPOSE: Levetiracetam (LEV) is a new compound with anticonvulsive efficacy in
      focal and generalized epilepsies. Recent in vitro studies suggest LEV to act as a
      selective N-type-calcium-channel blocker. METHODS: We used transcranial magnetic
      stimulation (TMS) in order to investigate if ion-channel blockade is relevant to
      the inhibitory CNS effects of LEV in vivo and if motor thresholds (MTs) are a
      valid TMS parameter to detect this mode of action. In a double blind, placebo
      controlled, crossover study, the effects of single oral doses of 500 and 2000 mg
      LEV on motor thresholds, recruitment curves (REC), cortical induced silent period
      (CSP) and on intracortical inhibition (ICI) and facilitation (ICF) were studied
      in 10 healthy subjects. RESULTS: A significant increase of motor thresholds was
      noticed after 2000 mg LEV as compared to placebo. The recruitment curve showed a
      trend towards motor evoked potential (MEP) amplitude reduction after LEV. LEV had
      no significant effect on CSP or on intracortical excitability as measured by
      inhibition and facilitation. CONCLUSIONS: We conclude that the modulation of ion
      channel function, reflected by motor threshold elevation and a trend towards
      recruitment curve suppression, is relevant to the inhibitory CNS effects of LEV
      in vivo, and therefore, may contribute to the anticonvulsive efficacy of LEV.
      GABAergic or glutamatergic mechanisms seem to be less important in vivo as
      measured by TMS.

PMID- 15519132
TI  - Refractory atypical absence seizures in rat: a two hit model.
AB  - Medically refractory seizure disorders in children usually have malignant
      neurodevelopmental outcomes and often are associated with the presence of
      congenital cortical dysplasias in the brain. To date, there are no animal models
      of these disorders by which to test hypotheses of pathogenesis or to screen novel
      drugs for antiepileptic activity. In rats, treatment with the antimitotic agent
      methylazoxymethanol acetate (MAM) on gestational day (G) 15 produces a neuronal
      migration disorder similar to the cortical dysplasias seen in human brain. We
      sought to produce chronic, recurrent, medically refractory seizures by
      administration of the cholesterol biosynthesis inhibitor AY-9944 (AY) during
      postnatal development in rats exposed prenatally to MAM. Prenatal MAM and
      postnatal AY treatments resulted in spontaneous, recurrent atypical absence
      seizures that were characterized by bilaterally synchronous slow spike-and-wave
      discharges (SWD) with a frequency of 6 Hz. The MAM-AY-induced seizures were
      refractory to ethosuximide, sodium valproate, and the GABABR antagonist CGP
      35348, and were exacerbated by carbamazepine. Histological examination of brains
      from MAM-treated rats showed hippocampal heterotopias, in addition to atrophy and
      abnormalities of cortical lamination. The MAM-AY-treated rat represents a
      reproducible model of refractory atypical absence seizures in children with brain
      dysgenesis.

PMID- 15519133
TI  - Effect of pentylenetetrazol-induced epileptic seizure on thiol redox state in the
      mouse cerebral cortex.
AB  - In the present study we examined the effects of pentylenetetrazol (PTZ)
      administration on the thiol redox state (TRS), lipid peroxidation and protein
      oxidation in left and right mouse cerebral cortex in order (a) to quantitate the
      major components of the thiol redox state and relate them with oxidative stress
      and cortical laterality, and (b) to investigate whether neuronal activation
      without synchronization, induced by subconvulsive doses of PTZ, can cause similar
      qualitative effects on the thiol redox state. Specifically, we examined the TRS
      components [glutathione (GSH), glutathione disulfide (GSSG), cysteine (CSH),
      protein (P) thiols (PSH) and protein and non-protein (NP) mixed/symmetric
      disulfides (PSSR, NPSSR, NPSSC, PSSP)]. At 15 min after seizure, GSH, GSSG, CSH,
      NPSSC, PSSR and PSSC levels are decreased in left (14-50%) and right (11-53%)
      cortex while PSSP levels are increased in both left (1400%) and right (1600%)
      cortex. At 30 min after seizure, GSSG, CSH, NPSSC, PSSR and PSSC levels are
      decreased in left (14-51%) and right (18-56%) cortex while PSSP and protein
      carbonyl levels are increased in left (2300% and 20%, respectively) and right
      (2800% and 21%, respectively) cortex. At 24 h after seizure, the TRS components
      return to normal and protein carbonyl levels are decreased in left (16%) and
      right (20%) cortex. The significant decrease in GSH, GSSG, CSH, NPSSC, PSSR and
      PSSC, as well as the increase in protein carbonyl and the high increase in PSSP
      levels after PTZ-induced seizure indicate increased oxidative stress in cerebral
      cortex of mice, and of similar magnitude and TRS-component profiles between left
      and right cerebral cortex.

PMID- 15519134
TI  - Predictors of epilepsy surgery outcome: a meta-analysis.
AB  - The potential efficacy of temporal and extratemporal resection in patients with
      partial epilepsy uncontrolled by anti-epileptic drugs is undisputed. However,
      there are still uncertainties about which patients will benefit most. A
      systematic review of the available literature has been undertaken by four pairs
      of reviewers to assess the overall outcome of epilepsy surgery and to identify
      factors better correlated to seizure outcome. A Medline search for studies on
      epilepsy surgery published since 1984 was performed. Studies were included if
      they had a well-defined population and design, a sample size of at least 30
      patients, an MRI performed in least 90% of cases, an expected duration of follow
      up of at least one year, and a post-operative outcome measured as seizure
      remission. A good outcome was considered as seizure control or seizure-free
      status for at least one year or Engel class I. Based on the review of 47 articles
      meeting all the eligibility criteria, febrile seizures (odds ratio, OR, 0.48; 95%
      confidence interval, CI, 0.27-0.83), mesial temporal sclerosis (OR 0.47; 95% CI
      0.35-0.64), tumors (OR 0.58; 95% CI 0.42-0.80), abnormal MRI (OR 0.44; 95% CI
      0.29-0.65), EEG/MRI concordance (OR 0.52; 95% CI 0.32-0.83), and extensive
      surgical resection (OR 0.24; 95% CI 0.16-0.36) were the strongest prognostic
      indicators of seizure remission (positive predictors); by contrast, post
      operative discharges (OR 2.41; 95% CI 1.37-4.27) and intracranial monitoring (OR
      2.72; 95% CI 1.60-4.60) predicted an unfavorable prognosis (negative predictors).
      Firm conclusions cannot be drawn for extent of resection, EEG/MRI concordance and
      post-operative discharges for the heterogeneity of study results.
      Neuromigrational defects, CNS infections, vascular lesions, interictal spikes,
      and side of resection did not affect the chance of seizure remission after
      surgery. Despite a number of limitations, the results of the review provide some
      insight into the selection of the best surgical candidates in clinical practice
      but raise concerns on the quality of published reports, and may serve as the
      basis for the identification of better standards to assess surgical outcome in
      observational studies.

PMID- 15519135
TI  - Ictal functional TCD for the lateralization of the seizure onset zone--a report
      of two cases.
AB  - Ictal functional transcranial Doppler sonography (I-fTCD) was used to lateralize
      the ictal onset zone in the presurgical evaluation of two patients with temporal
      lobe epilepsy. In one patient, I-fTCD and ictal SPECT were performed
      simultaneously during EEG-monitoring. In both patients, results were concordant
      with the ictal SPECT findings, PET and semiology. I-fTCD seems to be an
      interesting new method to non-invasively lateralize the seizure onset zone with
      high temporal resolution. I-fTCD and SPECT may give complementary information to
      lateralize the seizure onset zone.

PMID- 15519136
TI  - Chemokine receptors and melanoma metastasis.
AB  - Cancer metastasis is the end result of a complex series of biologic events that
      leads to the formation of clinically significant secondary tumors at distant
      sites. The sites of distant metastasis are not random since certain tumors show a
      tendency to develop metastases in specific organs. Human melanoma, for example,
      demonstrates frequent metastasis to brain, lungs, lymph nodes, and skin. Herein,
      we review the evidence that suggests that a limited number of chemokine receptors
      may play critical roles in determining organ-selective metastasis in melanoma by
      regulating diverse processes such as chemoattraction, adhesion, and survival. In
      particular, we describe roles for CC chemokine receptor 7 (CCR7) in lymph node
      metastasis, CXC chemokine receptor 4 (CXCR4) in pulmonary metastasis, and CCR10
      in skin metastasis, using a mouse model of melanoma. Preliminary evidence in this
      preclinical model suggests that inhibiting the function of these receptors may
      decrease the ability of cancer cells to disseminate to other sites and/or block
      their ability to survive and form tumors. Therefore, manipulation of the
      chemokine network could have therapeutic potential in human malignancies.

PMID- 15519137
TI  - Repetitive DNA alterations in human skin cancers.
AB  - Repetitive sequences constitute landmarks for genome regulation, evolution, and
      chromatin architecture. Patterns of specific and non-specific repetitive
      sequences change in many types and stages of tumor cells, characterized by band
      loss, gain, and (de) increased staining of pre-existing bands. In this work,
      repetitive DNA was studied in search of genome instability of skin cancers: basal
      and squamous cell carcinomas (BCC and SCC), malignant melanoma (MM), melanocytic
      nevus (MN), and actinic keratosis (AK) lesions. DNAs were extracted from blood
      and tumor samples from 21 BCC, 7 SCC, 11 MM and 7 lesions. Banding patterns were
      obtained by random amplification of polymorphic DNA (RAPD), and specific D9S50
      and D9S52 microsatellites (9p21). D9S50 patterns revealed microsatellite
      instability (MSI) and/or loss of heterozygosity (LOH) in 36% BCC, 25% SCC, and
      57% MM tumors. D9S52 microsatellite showed 28.5%; 42.8%; and 71.4% altered
      tumors, respectively. No microsatellite alterations were found in MN and AK. On
      the other hand, genomic rearrangements detected by RAPD were present in 100%
      tumors. In BCC, the mean number of tumor DNA alterations showed predominant gain
      of bands. On the contrary, MM samples presented loss, or decreased intensity
      signal of RAPD bands. Genome alterations in skin cancers would result from
      chromosomal rearrangements, aneuploidy and/or polysomies. The low-cost and quick
      RAPD technique may reveal unknown genes or DNA sequences associated with tumor
      development and progression, and may be easily implemented in clinical diagnosis.

PMID- 15519138
TI  - Effect of defensin peptides on eukaryotic cells: primary epithelial cells,
      fibroblasts and squamous cell carcinoma cell lines.
AB  - BACKGROUND: Although the usefulness of the antimicrobial peptides known as
      defensins has been suggested against oral and skin infections, possible adverse
      effects of the defensins on the host should be understood before clinical
      applications can be contemplated. OBJECTIVE: In the present study, we
      investigated how alpha-defensin (HNP-1) and beta-defensins (hBD-1, -2, -3) affect
      cells including primary epithelial cells, fibroblasts and squamous cell carcinoma
      cell lines, SCC-9 and KB. METHOD: Cell proliferation was assessed by the direct
      cell counting and XTT assay. RESULTS: We found that alpha-defensin promotes
      proliferation of the epithelial cells at low concentration but has a cytotoxic
      effect at high concentration. In contrast, beta-defensins have little effect on
      these cells at any concentration, suggesting that beta-defensins may have no
      adverse effects on the host. CONCLUSION: Therefore, in terms of host response
      beta-defensins may be more suitable antimicrobial agents for clinical
      applications than alpha-defensins.

PMID- 15519139
TI  - Modulation of androgen receptor transcriptional activity by anti-acne reagents.
AB  - BACKGROUND: To study the potential anti-androgenic activity of roxithromycin
      (RXM), we previously used human dermal fibroblasts transiently transfected with
      the expression vector of androgen receptor (AR) coactivator ARA55 as the in vitro
      model reflecting the end-organ hypersensitivity. OBJECTIVE: To examine the
      potential anti-androgenic activity of anti-acne therapeutic agents, nadifloxacin
      (NDFX), RXM, all-trans retinoic acid (atRA), and glycolic acid (GA), we carried
      out the transient transfection assays using the CV-1 cells as a more sensitive
      assay system. RESULTS: The result showed that 5 microg/ml of RXM suppress 10(-9)M
      R1881-induced AR transcriptional activity by 21.2%. 50 microg/ml of NDFX can
      suppress AR transcriptional activity to 29.8%. Furthermore, the assays with
      treatment of 1, 5, 10, or 50 microg/ml NDFX in the presence of 1 microg/ml RXM
      showed that 5, 10, or 50 microg/ml NDFX inhibits the AR transactivity by 32.7,
      31.1 or 61.0%, respectively, indicating the synergistic effect of NDFX and RXM.
      Besides 10(-5)M atRA suppressed the R1881-induced luciferase activity by 50%, but
      GA did not alter AR transactivity. CONCLUSIONS: We demonstrated that anti-acne
      agents available in the clinical practice can exert anti-androgenic effects in
      the treatment of acne.

PMID- 15519140
TI  - Identification of PUVA-inducible genes in primary cultured dermal fibroblasts
      using suppression subtractive hybridization.

PMID- 15519142
TI  - TNF-238A is associated with juvenile onset psoriasis in patients of Han
      population in Southwest China.

PMID- 15519141
TI  - Investigation on the IVS5 +5G --> a splice site mutation of HPS1 gene found in
      Japanese patients with Hermansky-Pudlak syndrome.

PMID- 15519143
TI  - Interferon-beta confers on mouse macrophages a resistance to glucocorticoid
      suppression of inducible nitric-oxide synthase mRNA expression.

PMID- 15519144
TI  - Mannose-binding lectin polymorphisms in patients with Behcet's disease.

PMID- 15519145
TI  - Differential regulation of the secretion of vascular endothelial growth factor
      from human skin fibroblasts by growth factors and cytokines.

PMID- 15519146
TI  - Exclusion of the TAP1 and TAP2 genes within the HLA class II region as candidate
      susceptibility genes to pemphigus in the Japanese population.

PMID- 15519147
TI  - Molecular typing of Trichophyton tonsurans by PCR-RFLP of the ribosomal DNA
      nontranscribed spacer region.

PMID- 15519148
TI  - Sphingolipids as coenzymes in anion transfer and tumor death.
AB  - Many kinds of natural sphingolipids and their analogs stimulate or inhibit a wide
      assortment of biochemical phenomena and enzymes. The puzzle considered here is:
      how can these lipids control so many different kinds of processes? In almost
      every study in which a structural comparison was made, an allylic alcohol moiety
      [-CH=CH-CH(OH)-] was found to be an essential feature of the sphingolipid. Many
      of those stimulations lead to cell death, emphasizing the importance of allylic
      sphingolipid structure in the design of chemotherapeutic agents. The proposal
      offered here is that these lipids function as coenzymes, in which the allylic
      moiety acts as an anion transferring agent, forming transient phosphate or acyl
      or peptidyl esters for the synthesis or hydrolysis of phosphoproteins, proteins,
      and phospholipids. Sphingolipids that inhibit these reactions may simply displace
      the active sphingolipids from their sites in the enzymes' active regions, or bind
      to the enzymes' allosteric region. This kind of competition could act as a major
      homeostatic control mechanism. Some of the allylic sphingolipids also generate
      reactive oxygen, possibly by oxidation of the allylic alcohol group. This
      explains the need to control redox-controlling metabolites in sphingolipid
      controlled processes (e.g., glutathione). Many anticancer drugs that produce
      apoptosis in tumors possess an allylic alcohol residue, affect protein
      phosphorylation, and produce reactive oxygen species. They may be therapeutically
      useful because they control the action of sphingolipids as anion transfer
      agonists or inhibitors.

PMID- 15519149
TI  - Solution chemistry and cytotoxic properties of novel organogold(III) compounds.
AB  - The solution behaviour of some novel organogold(III) compounds was investigated,
      and their cytotoxic properties evaluated against a few human tumour cell lines
      (A2780/S, A2780/R, MCF7, HT29 and A549). Specifically, the following compounds
      were considered: [Au(bipy(dmb)-H)(2,6-xylidine-H)][PF(6)] (AuXyl) and
      [Au(bipy(dmb)-H)(p-toluidine-H)][PF(6)] (AuTol) (in which bipy(dmb)=6-(1,1
      dimethylbenzyl)-2,2'-bipyridine), [Au(py(dmb)-H)(AcO)(2)] (AuPyAcO) (in which
      py(dmb)=2-(1,1-dimethylbenzyl)-pyridine) and [Au(pz(Ph)-H)Cl(3)]K (AuPzCl) (in
      which pz(Ph)=1-phenylpyrazole). The solution chemistry of these compounds, under
      physiological-like conditions, was investigated through UV-vis absorption and
      (1)H NMR spectroscopies. Significant cytotoxic effects in vitro were observed in
      selected cases.

PMID- 15519150
TI  - Inhibition of human beta-tryptase by Bowman-Birk inhibitor derived peptides:
      creation of a new tri-functional inhibitor.
AB  - Bowman-Birk inhibitor proteins (BBIs), which are potent inhibitors of
      chymotrypsin-like proteases, do not inhibit human beta-tryptase despite this
      protein having a chymotrypsin-like fold. We have reported previously that, in
      contrast, BBI-derived peptides (whose sequences incorporate the solvent exposed
      reactive site loop motif) are able to inhibit human beta-tryptase. This is due to
      their small size, which allows them to access the restricted active site(s) of
      tryptase, which has an unusual tetrameric arrangement with four active sites
      flanking a central pore. In this paper, we have examined the possibility of
      creating additional interactions within this pore by adding extensions to the BBI
      peptide motif. We have taken the core disulfide-bridged sequence SCTKSIPPQCY and
      examined a series of extensions, at both the C- and N-termini, that bear a second
      positively charged Lys residue at their end. The aim was to construct inhibitors
      that could make additional interactions in tryptase by spanning the gap between
      adjacent active sites in the enzyme, producing a double-headed inhibitor; a
      positively charged group was used as the dominant specificity of this enzyme is
      for a positively charged P1 residue. Both N- and C-terminal extensions are found
      to produce inhibitors of much increased potency, with a strong dependence of
      potency on chain length. Moreover, it was found that the C- and N-terminal
      extensions were able to synergise, with their combination on the same peptide
      producing an even better inhibitor with a potency 10(4)-fold greater than the
      original sequence. We suggest that the C- and N-terminal extensions are picking
      up interactions with separate additional sites on the tryptase, making the doubly
      extended BBI peptide a tri-functional tryptase inhibitor.

PMID- 15519151
TI  - Synthesis and structure-activity relationships of potent 3- or 4-substituted-2
      cyanopyrrolidine dipeptidyl peptidase IV inhibitors.
AB  - Dipeptidyl peptidase IV (DPP-IV) inhibitors have attracted attention as potential
      drugs for use in the treatment of type 2 diabetes because they prevent
      degradation of glucagon-like peptide-1 (GLP-1) and extend its duration of action.
      A series of 2-cyanopyrrolidines are among the most potent of DPP-IV inhibitors.
      We focused our attention on substitutions at the 3- or 4-position of 2
      cyanopyrrolidines and synthesized and evaluated various derivatives. Among them,
      the 4-fluoro derivative was found to exhibit better DPP-IV inhibitory activity
      and higher plasma drug concentrations after oral administration to rats than the
      4-unsubstituted derivative. We report here on the synthesis and biological data
      of the aforementioned derivatives.

PMID- 15519152
TI  - The synthesis of phosphorylated disaccharide components of the extracellular
      phosphomannan of Pichia (Hansenula) holstii NRRL Y-2448.
AB  - Methods for the stereoselective synthesis of alpha-(1-->2)- and alpha-(1-->3)
      linked 6(II)-O-phosphomannobiosides were developed. Two strategies were
      successfully employed: a D-mannosyl acceptor was coupled with a phosphorylated D
      mannosyl trichloroacetimidate donor, or alternatively with a differentially 6-O
      protected D-mannosyl trichloroacetimidate donor which, after glycosylation, was
      selectively deprotected and phosphorylated. Two target phosphomannobiosides
      intended for use in SAR studies of the antiangiogenic drug candidate PI-88, 2-O
      (6-O-phospho-alpha-D-mannopyranosyl)-D-mannopyranose and methyl 3-O-(6-O-phospho
      alpha-D-mannopyranosyl)-alpha-D-mannopyranoside, were synthesized. The former is
      a minor component of the side-chain repeating unit of the extracellular
      phosphomannan of Pichia (Hansenula) holstii NRRL Y-2448, whilst the latter
      represents a nonreducing end fragment of the phosphomannan.

PMID- 15519153
TI  - Preparation and preliminary biological evaluation of a 177Lu labeled sanazole
      derivative for possible use in targeting tumor hypoxia.
AB  - The preparation of a polyazamacrocyclic-nitrotriazole conjugate for radiolabeling
      with the therapeutic radioisotope viz. (177)Lu is described. The nitroimidazole
      used for the present study is [N-2'(carboxyethyl)-2-(3'-nitro-1'
      triazolyl)acetamide], the carboxylic acid derivative of sanazole, which possesses
      an optimal combination of desired properties such as, selective toxicity for
      hypoxic cells, lowered lipophilicity resulting in lowered neurotoxicity. The
      bifunctional chelating agent is a DOTA derivative viz. 1,4,7,10-tetraaza-1-(4'
      aminobenzylacetamido)-cyclododecane-4,7,10- triacetic acid (p-amino-DOTA
      anilide). (177)Lu was produced in adequate specific activity (110TBq/g) and high
      radionuclidic purity (approximately 100%) by irradiating enriched (60.6% (176)Lu)
      Lu(2)O(3) target and used for radiolabeling of the sanazole-BFCA conjugate.
      approximately 98% Complexation yield was achieved under optimized conditions. The
      complex has been characterized by paper chromatography and HPLC studies.
      Bioevaluation studies in Swiss mice bearing fibrosarcoma tumors revealed moderate
      tumor uptake (0.88%/g at 1h post-injection) with favorable tumor to blood (4.00
      at 1h post-injection) and tumor to muscle (4.63 at 1h post-injection) ratios.

PMID- 15519154
TI  - Flexible docking of pyridinone derivatives into the non-nucleoside inhibitor
      binding site of HIV-1 reverse transcriptase.
AB  - Potent non-nucleoside reverse transcriptase inhibitors (NNRTIs) of the pyridinone
      derivative type were docked into nine NNRTIs binding pockets of HIV-1 reverse
      transcriptase (RT) structures. The docking results indicate that pyridinone
      analogues adopt a butterfly conformation and share the same binding mode as the
      crystal inhibitors in the pocket geometries of nevirapine, 1051U91, 9-Cl-TIBO, Cl
      alpha-APA, efavirenz, UC-781, and S-1153. The results are in agreement with the
      data concerning mutational and structure-activity relationships available for
      pyridinone analogues and aid in the understanding, at the molecular level, of the
      biological response of published hybrid pyridinone molecules. Strategies to
      design further pyridinone derivatives active against RT containing mutations are
      discussed.

PMID- 15519155
TI  - Chrysin and its phosphate ester inhibit cell proliferation and induce apoptosis
      in Hela cells.
AB  - To improve the biological activities of chrysin (CR), we synthesize Diethyl
      Chysin-7-yl phosphate (CPE: C(19)H(19)O(7)P) and tetraethyl bis-phosphoric ester
      of chrysin (CP: C(23)H(28)O(10)P(2)) through a simplified Atheron-Todd reaction.
      The interactions of the CR and CPE with lysozyme were explored by electrospray
      ionization mass spectrometry (ESI) and fluorescence spectrometry method.
      Experimental results indicate that CPE could form the noncovalent compound with
      lysozyme, while the interaction of the CR with lysozyme was not detected. In
      addition, whether and how the compounds CPE and CP affect proliferation and
      apoptosis in human cervical cancer Hela cells were investigated. Moreover, the
      effects of CPE and CP in Hela cells were compared with that of the nonmodified CR
      compound. The Hela cells were co-cultured with CR, CP, and CPE as experimental
      groups, respectively, and corresponding control groups treated without CR, CP,
      and CPE. The proliferation and apoptosis were detected using MTT assay, HCl
      denatured-methyl green-pyronin staining, PCNA immunohistochemistry and TUNEL
      techniques. The cell growth IC(50), relative absorbance (RA), proliferating index
      (PI), PCNA-IR (immunoreactivity IR) integration value (IV), and apoptosis index
      (AI) were calculated and their correlation was analyzed in each group. The
      results show that all CR, CP, and CPE could inhibit proliferation and induce
      apoptosis in Hela cells. Moreover, the effects of CP and CPE were more potent
      than that of CR. The CP and CPE were proved to be a kind of stronger apoptosis
      inducers than nonphosphated CR. There was a negative correlation between
      proliferation and apoptosis. In conclusion, the CR, CP, and CPE could effectively
      inhibit growth by down-regulated expression of PCNA, and induce apoptosis in Hela
      cells. The efficiency of the modified CP and CPE preceded nonmodified CR
      compounds. The CP and CPE may be a new potential anti-cancer drug for therapy of
      human cervical carcinoma.

PMID- 15519156
TI  - Ionization, lipophilicity, and molecular modeling to investigate permeability and
      other biological properties of amlodipine.
AB  - This paper uses a recent approach toward drug discovery, in which in silico tools
      and experimental data are combined together to study the structural features of
      amlodipine and their relevance in the peculiar pharmacodynamic and
      pharmacokinetic profiles of this long acting calcium antagonist. Results reveal
      for amlodipine two families of conformers (folded and extended) but also
      demonstrate that protonation is the predominant factor governing amlodipine
      intermolecular interactions among which ionic forces play a major role.

PMID- 15519157
TI  - Fluorescent epsilon-ATP analogues for probing physicochemical properties of
      proteins. Synthesis, biochemical evaluation, and sensitivity to properties of the
      medium.
AB  - Despite the significance of the elucidation of proteins' physicochemical
      parameters to understand various molecular phenomena, direct methods for
      measuring these parameters are not readily available. Here, we propose the use of
      8-[p-amino-Ph]-epsilon-ATP, 3b, as a fluorescent probe for the elucidation of
      physicochemical parameters of binding sites in certain proteins. We synthesized
      novel fluorescent nucleotide analogues based on an extension of the epsilon-ATP
      scaffold. These analogues bear a primary or tertiary p-amino-phenyl moiety on the
      etheno-bridge. We explored the recognition of the fluorescent analogues by the
      target proteins: P2Y(1)-receptor (P2Y(1)-R) and NTPDase1. Based on the high
      affinity to the P2Y(1)-R (EC(50) 100nM), 3b proved a suitable probe for the
      investigation of this receptor. Next, we elucidated the dependencies of the
      absorption and emission spectra of 3b on environmental parameters, for
      establishing correlation equations. These equations will help determine the
      properties of the ATP-binding site from the spectral data of the protein-bound
      3b. For this purpose, the sensitivity of the probe to acidity, dielectricity, H
      bonding, viscosity, and to correlation between these parameters was determined.
      Thus, the pH-dependence of 3b emission intensity is bell shaped. At pH2.8 the
      quantum yield (phi) is enhanced 150-fold, as compared to neutral pH. The basic
      nitrogen atoms of 3b were assigned and pK(a) values were determined. A linear
      relationship was found between log phi and log viscosity, however, emission
      maxima (lambda(max)) remained constant. A linear relationship was found between
      both phi and lambda(max) and dielectricity, as measured in protic or aprotic
      solvents of comparable viscosity. pK(a)-like values were measured in acid
      titrated alcohols with varying dielectricity but comparable viscosity, or with
      varying viscosity but comparable dielectricity. An inverse relationship and a
      linear relationship were found between the pK(a) values of 3b and the medium
      dielectricity and viscosity, respectively. These correlations help the
      calibration of properties of a protein ATP-binding site.

PMID- 15519158
TI  - Quantitative structure-activity relationship study using refractotopological
      state atom index on some neonicotinoid insecticides.
AB  - Importance of atom-level topological descriptors like electrotopological state
      atom (E-state) index in QSAR study is increasing. These descriptors help to
      relate structure and activity at atomic/fragmental level. In view of the earlier
      success of E-state index on some azidopyridinyl neonicotinoid insecticides, a
      relatively new atom-level topological descriptor; refractotopological state atom
      (R-state) index was used in this work. This was used to identify the important
      atoms/fragments related to dispersive/van der Waals interactions of
      neonicotinoids with the nicotinic acetylcholine receptor (nAChR). This study
      showed the structural requirements for the mammal alpha(4)beta(2) and Drosophila
      nAChR agonistic activity. It also revealed that substituted imine, nitromethylene
      at X-position were selective to the insecticidal activity. Azido substitution at
      pyridine ring of neonicotinoids disfavored the binding with the receptors. This
      study confirmed the validity of the R-state index as a new tool for quantitative
      structure-activity relationships. It has the ability to find out the required
      structural features as well as to predict the activity of the neonicotinoids.

PMID- 15519159
TI  - Syntheses and bioactivities of macrocyclic paclitaxel bis-lactones.
AB  - Five macrocyclic paclitaxel bis-lactones and their corresponding open chain
      taxoids were synthesized as models of the tubulin-binding conformation of
      paclitaxel. Macrocyclic lactones with a 19-21-membered ring underwent
      isomerization to form smaller rings. The lactones were evaluated for cytotoxicity
      and tubulin-polymerization ability. All five macrocyclic paclitaxel lactones were
      active, but less so than paclitaxel, while the rearranged macrocyclic lactones
      and the corresponding open-chain taxoids were much less active or inactive.

PMID- 15519160
TI  - Synthesis and structure-activity correlations of the cytotoxic bifunctional 1,4
      diamidoanthraquinone derivatives.
AB  - Anthraquinone-based compounds are attractive target for the design of new
      anticancer drugs. We have previously described a series of 1,5- and 1,4
      difunctionalized anthraquinones, which exhibit different spectra of potency,
      together with human telomerase evaluation. The present study details the
      preparation of further, distinct series of regioisomeric difunctionalized
      amidoanthraquinone and examines their in vitro cytotoxicity in C6, Hepa G2, and
      2.2.15 cell lines. Two structurally related compounds, mitoxantrone and
      adriamycin, were tested in parallel as positive controls. The structure-activity
      relationships indicated amido substitution may lead to a different mechanism of
      cytotoxicity. Compounds, which have -(CH2)n- side chains terminating in basic
      groups such as aminoalkyl-substituted, showed cytotoxic activity in several cell
      lines. The exact mode of intercalative binding may be dictated by the positional
      placement of substituent side chains. Implications for amidoanthraquinone
      cytotoxicity as potential anticancer agents are discussed. In addition, we
      further delineate the nature of the pharmacophore for this class of compounds,
      which provides a rational basis for the structure-activity relationships.

PMID- 15519161
TI  - Studies of nonnucleoside HIV-1 reverse transcriptase inhibitors. Part 1: Design
      and synthesis of thiazolidenebenzenesulfonamides.
AB  - A random high-throughput screening (HTS) program to discover novel nonnucleoside
      reverse transcriptase inhibitors (NNRTIs) has been carried out with MT-4 cells
      against a nevirapine-resistant virus, HIV-1(IIIB-R). The primary hit, a
      thiazolidenebenzenesulfonamide derivative, possessed good activity. A systematic
      modification program examining various substituents at the 3-, 4-, and 5
      positions on the thiazole ring afforded compounds with enhanced anti-HIV-1 and
      reverse transcriptase (RT) inhibitory activities. These results confirm the
      important role of the substituents at these positions and the
      thiazolidenebenzenesulfonamide motif as a valuable lead series for the next
      generation NNRTIs.

PMID- 15519162
TI  - A DFT-based QSARs study of protoporphyrinogen oxidase inhibitors: phenyl
      triazolinones.
AB  - The equilibrium geometries, electronic structures, and electrostatic potentials
      of a series of substituted phenyl triazolinones, a kind of important
      protoporphyrinogen oxidase (Protox) inhibitors, had been investigated using
      density functional theory (DFT) method at the B3LYP/6-31G(d,p) basis set. The
      quantum chemical descriptors, such as energy difference (DeltaE) between the
      lowest unoccupied molecular orbital and the highest occupied molecular orbital,
      electrophilic and nucleophilic frontier electron density (f(i)(E) and f(i)(N)),
      and net atomic charge (Q(i)), were computed at the same DFT level. Based on these
      useful quantum chemical descriptors, the quantitative structure-activity
      relationships was carried out and the results showed that descriptors, Q(C11),
      f(N5)(E), f(C10)(N), f(O6)(E), f(C11)(N), and DeltaE, were most likely to be
      responsible for the in vitro biological activity and the greenhouse pre-emergence
      activity of phenyl triazolinones. The descriptors accounted for 77-86% of the
      variation in the in vitro biological activity among the herbicidal phenyl
      triazolinone analogs 1-26 (except compounds 19 and 20). The results of the
      regression analysis showed that the activity was parabolically related not only
      with the descriptor f(O6)(E), but also with the descriptor f(C11)(N) . The
      optimum values of the terms f(O6)(E) and f(C11)(N) were about 11.15 and 0,
      respectively. Studies also showed that compound 19 exhibiting the highest in
      vitro activity mimicked the three-ring portion of protoporphyrinogen IX
      (Protogen). The present work had proved that the DFT-based quantum chemical
      descriptors could lead to the better correlation relationship than that the PM3
      based electronic descriptors, therefore, DFT-based QSARs could be expected to
      help facilitate the design of additional substituted phenyl triazolinone
      derivatives of Protox inhibitors with good biological activity.

PMID- 15519163
TI  - Molecular docking and 3D QSAR studies on 1-amino-2-phenyl-4-(piperidin-1-yl)
      butanes based on the structural modeling of human CCR5 receptor.
AB  - In the present study, we have used an approach combining protein structure
      modeling, molecular dynamics (MD) simulation, automated docking, and 3D QSAR
      analyses to investigate the detailed interactions of CCR5 with their antagonists.
      Homology modeling and MD simulation were used to build the 3D model of CCR5
      receptor based on the high-resolution X-ray structure of bovine rhodopsin. A
      series of 64 CCR5 antagonists, 1-amino-2-phenyl-4-(piperidin-1-yl)-butanes, were
      docked into the putative binding site of the 3D model of CCR5 using the docking
      method, and the probable interaction model between CCR5 and the antagonists were
      obtained. The predicted binding affinities of the antagonists to CCR5 correlate
      well with the antagonist activities, and the interaction model could be used to
      explain many mutagenesis results. All these indicate that the 3D model of
      antagonist-CCR5 interaction is reliable. Based on the binding conformations and
      their alignment inside the binding pocket of CCR5, three-dimensional structure
      activity relationship (3D QSAR) analyses were performed on these antagonists
      using comparative molecular field analysis (CoMFA) and comparative molecular
      similarity analysis (CoMSIA) methods. Both CoMFA and CoMSIA provide statistically
      valid models with good correlation and predictive power. The q(2)(r(cross)(2))
      values are 0.568 and 0.587 for CoMFA and CoMSIA, respectively. The predictive
      ability of these models was validated by six compounds that were not included in
      the training set. Mapping these models back to the topology of the active site of
      CCR5 leads to a better understanding of antagonist-CCR5 interaction. These
      results suggest that the 3D model of CCR5 can be used in structure-based drug
      design and the 3D QSAR models provide clear guidelines and accurate activity
      predictions for novel antagonist design.

PMID- 15519164
TI  - Pyrazole derivatives as new potent and selective 20-hydroxy-5,8,11,14
      eicosatetraenoic acid synthase inhibitors.
AB  - Improvement of the physical properties of pyrazole derivative 1, which we
      reported previously as a potent and selective 20-HETE synthase inhibitor (IC(50)
      5.7 nM), is described. Introduction of a sufficient substituted-amino group on
      the side chain enhanced the water-solubility of 1 (0.014 mg/mL at pH 6.8). Among
      the products, 2-piperazinoethoxy derivatives 3e and 6b showed solubility suitable
      for injection and potent inhibitory activity toward 20-HETE synthase (IC(50) 21.2
      and 14.0 nM, respectively).

PMID- 15519165
TI  - A novel class of achiral seco-analogs of CC-1065 and the duocarmycins: design,
      synthesis, DNA binding, and anticancer properties.
AB  - The synthesis, DNA binding properties, and in vitro and in vivo anticancer
      activity of fifteen achiral seco-cyclopropylindoline (or achiral seco-CI) analogs
      (5a-o) of CC-1065 and the duocarmycins are described. The achiral seco-CI analogs
      contain a 4-hydroxyphenethyl halide moiety that is attached to a wide range of
      indole, benzimidazole, pyrrole, and pyridyl-containing noncovalent binding
      components. The 4-hydroxyphenethyl halide moiety represents the simplest mimic of
      the seco-cyclopropylpyrroloindoline (seco-CPI) pharmacophore found in the natural
      products, and it lacks a chiral center. The sequence and minor groove specificity
      of the achiral compounds was ascertained using a Taq DNA polymerase stop assay
      and a thermal induced DNA cleavage experiment using either a fragment of pBR322
      or pUC18 plasmid DNA. For example, seco-CI-InBf (5a) and seco-CI-TMI (5c)
      demonstrated specificity for AT-rich sequences, particularly by reacting with the
      underlined adenine-N3 position of 5'-AAAAA(865)-3'. This is also the sequence
      that CC-1065 and adozelesin prefer to alkylate. The achiral seco-CI compounds
      were subjected to cytotoxicity studies against several human (K562, LS174T, PC3,
      and MCF-7) and murine cancer cell lines (L1210 and P815). Following continuous
      drug exposure, the achiral compounds were found to be cytotoxic, with IC(50)
      values in the muM range. Interestingly, the carbamate protected compound 5p was
      significantly less cytotoxic than agent 5c, supporting the hypothesis that loss
      of HCl and formation of a spiro[2,5]cyclopropylcyclohexadienone intermediate is
      necessary for biological activity. The achiral seco-CI compounds 5a and 5c were
      submitted to the National Cancer Institute for further cytotoxicity screening
      against a panel of 60 different human cancer cell lines. Both compounds showed
      significant activity, particularly against several solid tumor cell lines. Flow
      cytometry studies of P815 cells that were incubated with compound 5c at its
      IC(50) concentration for 24h showed induction of apoptosis in a large percentage
      of cells. Compounds 5a and 5c were selected by the NCI for an in vivo anticancer
      hollow-fiber test, and received composite scores of 18 and 22, respectively.
      These two compounds were subsequently evaluated for in vivo anticancer activity
      against the growth of a human advanced stage SC UACC-257 melanoma in skid mice.
      At a dose of 134 mg/kg administered IP, compound 5c gave a T/C value of 40% (for
      day 51), and the median number of days of doubling tumor growth was 27.7, versus
      15.8 for untreated animals. For compound 5a, at 200mg/kg, the T/C was 58% and the
      median number of days of doubling tumor growth was 20.0 versus 8.7 for untreated
      animals. At these doses no toxicity or weight loss was observed for either
      compound. Furthermore, compound 5c was not toxic to murine bone marrow cell
      growth in culture, at a dose that was toxic for the previously reported seco-CBI
      (cyclopropylbenzoindoline)-TMI (4).

PMID- 15519166
TI  - Synthesis and biological evaluation of 5R- and 5S-methyl substituted D- and L
      configuration 1,3-dioxolane nucleoside analogs.
AB  - 1,3-Dioxolane and 1,3-oxathiolane nucleoside analogs play an important role in
      anti-viral and anti-neoplastic chemotherapy. We report here the synthesis of 2
      hydroxymethyl-5-methyl-1,3-dioxolanylpurine nucleosides from 4-acetoxy-2
      (benzyloxymethyl)-5-methyldioxolane. Dioxolanes of alpha-D-, beta-D-, alpha-L-,
      and beta-L-configuration were prepared, that included 5-methyl derivatives of
      both 5R and 5S configuration. Molecular mechanics calculations indicate that the
      5S and 5R diastereoisomeric 1,3-dioxolanes possess distinct conformational bias,
      suggesting that methyl substitution may alter the conformational preference of
      1,3-dioxolanes. The ability of the 1,3-dioxolanes to inhibit HCV RNA replication
      was evaluated in a cell-based, subgenomic replicon assay. In addition, activity
      against vaccinia and HIV was evaluated in cell-based assays. The 2-hydroxymethyl
      5-methyl-1,3-dioxolanes were found to be inactive.

PMID- 15519167
TI  - Serendipitous discovery of an unexpected rearrangement leads to two new classes
      of potential protease inhibitors.
AB  - The pathogenesis of a range of human diseases arises from the aberrant activity
      of proteolytic enzymes. Agents capable of selectively modulating the activity of
      these enzymes are of potential therapeutic value. Thus, there is a continuing
      need for the design of scaffolds that can be used in the development of new
      classes of protease inhibitors. We describe herein the serendipitous discovery of
      an unexpected rearrangement that leads to the formation of two novel templates
      that can be used in the design of protease inhibitors.

PMID- 15519168
TI  - Carboxylic acid and phosphate ester derivatives of fluconazole: synthesis and
      antifungal activities.
AB  - Two classes of fluconazole derivatives, (a) carboxylic acid esters and (b) fatty
      alcohol and carbohydrate phosphate esters, were synthesized and evaluated in
      vitro against Cryptococcus neoformans, Candida albicans, and Aspergillus niger.
      All carboxylic acid ester derivatives of fluconazole (1a-l), such as O-2
      bromooctanoylfluconazole (1g, MIC=111 microg/mL) and O-11
      bromoundecanoylfluconazole (1j, MIC=198 microg/mL), exhibited higher antifungal
      activity than fluconazole (MIC > or = 4444 microg/mL) against C. albicans ATCC
      14053 in SDB medium. Several fatty alcohol phosphate triester derivatives of
      fluconazole, such as 2a, 2b, 2f, 2g, and 2h, exhibited enhanced antifungal
      activities against C. albicans and/or A. niger compared to fluconazole in SDB
      medium. For example, 2-cyanoethyl-omega-undecylenyl fluconazole phosphate (2b)
      with MIC value of 122 microg/mL had at least 36 times greater antifungal activity
      than fluconazole against C. albicans in SDB medium. Methyl-undecanyl fluconazole
      phosphate (2f) with a MIC value of 190 microg/mL was at least 3-fold more potent
      than fluconazole against A. niger ATCC 16404. All compounds had higher estimated
      lipophilicity and dermal permeability than those for fluconazole. These results
      demonstrate the potential of these antifungal agents for further development as
      sustained-release topical antifungal chemotherapeutic agents.

PMID- 15519170
TI  - Bisquaternary caracurine V and iso-caracurine V salts as ligands for the muscle
      type of nicotinic acetylcholine receptors: SAR and QSAR studies.
AB  - The binding constants (K(i) values) of 24 caracurine V and 6 iso-caracurine V
      analogues for the muscle type of nicotinic ACh receptors (nAChR) from Torpedo
      californica were determined in a binding assay using (+/-)-[(3)H]epibatidine as a
      radioligand. The allyl alcohol group present in the iso-caracurine V ring system
      was found to be essential for high binding affinity. The most potent compounds
      are the dimethyl and di-(4-nitrobenzyl)-iso-caracurinium V salts 29 (18 nM), and
      31 (79 nM), respectively. Compound 29 and the corresponding diallyl analogue 30
      (350 nM) exhibited similar binding affinities as the equally substituted
      neuromuscular-blocking agents toxiferine I (14 nM) and alcuronium (234 nM),
      respectively. The SAR results were confirmed by QSAR studies, which additionally
      revealed that the presence of hydrogen-bond acceptor groups close to the
      quaternary nitrogen, is detrimental for the nicotinic binding affinity. The
      diallyl- and dimethylcaracurinium V salts 13 and 27, respectively, which are
      known to be among the most potent allosteric modulators of M(2) receptors
      (EC(50)=10 and 8nM, respectively), exhibited rather low nicotinic binding
      affinities for muscle type nAChR (K(i)=1.5 and 5.2 microM, respectively). Such a
      large difference in affinity suggests that it is possible to develop compounds
      with high muscarinic allosteric potency and low or negligible affinities for
      (alpha1)(2)beta1gammadelta nAChR. Additionally, the iso-caracurine V analogues
      with binding affinities comparable to those of (+)-tubocurarine and alcuronium
      could become a new class of neuromuscular-blocking agents.

PMID- 15519169
TI  - New lupane triterpenoids from Solidago canadensis that inhibit the lyase activity
      of DNA polymerase beta.
AB  - Bioassay-directed fractionation of a methyl ethyl ketone extract of Solidago
      canadensis L. (Asteraceae), using an assay to detect the lyase activity of DNA
      polymerase beta, resulted in the isolation of the four new lupane triterpenoids 1
      4 and the seven known compounds lupeol, lupeyl acetate, ursolic acid,
      cycloartenol, cycloartenyl palmitate, alpha-amyrin acetate, and stigmasterol. The
      structures of the new compounds were established as 3beta-(3R
      acetoxyhexadecanoyloxy)-lup-20(29)-ene (1), 3beta-(3-ketohexadecanoyloxy)-lup
      20(29)-ene (2), 3beta-(3R-acetoxyhexadecanoyloxy)-29-nor-lupan-20-one (3), and
      3beta-(3-hetohexadecanoyloxy)-29-nor-lupan-20-one (4), respectively, on the basis
      of extensive 1D and 2D NMR spectroscopic interpretation and chemical modification
      studies. All 11 compounds were inhibitory to the lyase activity of DNA polymerase
      beta.

PMID- 15519171
TI  - Synthesis and topoisomerase I inhibitory properties of luotonin A analogues.
AB  - Luotonin A, a naturally occurring pyrroloquinazolinoquinoline alkaloid, has been
      previously demonstrated to be a topoisomerase I poison. A number of luotonin A
      derivatives have now been prepared through the condensation of anthranilic acid
      derivatives and 1,2-dihydropyrrolo[3,4-b]quinoline-3-one in the presence of
      phosphorus oxychloride. When dichloromethane was used as solvent the reaction
      proceeded to a single product. In contrast when the reaction was carried out in
      tetrahydrofuran or in phosphorus oxychloride, an additional isomeric product was
      obtained. The luotonin A analogues were evaluated for their ability to effect
      stabilization of the covalent binary complex formed between human topoisomerase I
      and DNA, and for cytotoxicity toward a yeast strain expressing the human
      topoisomerase I.

PMID- 15519172
TI  - Structural requirements for 2,4- and 3,6-disubstituted pyran biomimetics of cis
      (6-benzhydryl-piperidin-3-yl)-benzylamine compounds to interact with monoamine
      transporters.
AB  - In our effort to delineate novel pharmacophoric configuration of bioisosteric
      pyran versions of cis-(6-benzhydryl-piperidin-3-yl)-benzylamine derivatives in
      interacting with the monoamine transporter, further structure-activity
      relationship study was carried out. Both cis and trans 2,4- and 3,6-disubstituted
      derivatives were synthesized to determine the positional importance of N
      substitution on affinity for monoamine transporters, that is the dopamine
      transporter (DAT), the serotonin transporter (SERT), and the norepinephrine
      transporter (NET) in rat brain. For that purpose, the potency of compounds was
      determined in competing for the binding of [(3)H]WIN 35,428, [(3)H]citalopram,
      and [(3)H]nisoxetine, respectively. Selected compounds were also evaluated for
      their activity in inhibiting the uptake of [(3)H]DA by DAT. Our binding results
      demonstrated potency in 3,6-disubstituted derivatives while 2,4-disubstituted
      derivatives failed to exhibit any appreciable binding affinity. Further
      structural exploration of the exocyclic N-atom in 3,6-disubstituted derivatives
      produced compounds potent at both DAT and NET. Compounds 16h and 16o with
      hydroxyl and amino groups in the phenyl moiety of the benzyl group produced the
      highest activity for the NET. In this regard, compound 16e with a methoxy
      substituent produced weak affinity at NET, which upon conversion into a hydroxyl
      functionality as in 16h produced potent affinity for the NET. Various indole
      derivatives displayed different interactions; the 5-substituted indole derivative
      16n exerted potent affinity for NET, confirming the bioisosteric equivalence
      between this indole moiety and the phenyl-4-hydroxy group in 16h.

PMID- 15519173
TI  - Direct percutaneous valve replacement: the next step?

PMID- 15519174
TI  - Redo antireflux surgery--the importance of a tailored approach.
AB  - OBJECTIVE: Although several studies have examined early outcome following redo
      antireflux surgery, there is little data on the long-term efficacy of these
      procedures. We reviewed our experience of these operations in order to assess the
      long-term results which can be achieved by choosing redo antireflux procedures
      based on the results obtained from pre-operative oesophageal function testing.
      METHODS: The case notes of 26 patients who underwent a repeat antireflux
      procedure between 1981 and 2000 were reviewed. Clinical history, examination,
      endoscopy, pH studies, oesophageal manometry and video barium contrast studies
      were performed on all patients prior to re-operation. In all cases, a
      standardised pre-formulated algorithm, based on the results of the pre-operative
      oesophageal function tests, was used to determine the choice of surgical
      procedure. Post-operatively, patients were classified into three groups: Group A
      (those with no symptoms), Group B (symptoms controlled by medication) and Group C
      (symptoms refractory to medical treatment). Patients in Groups B and C underwent
      repeat oesophageal function studies. RESULTS: In all cases, the indication for re
      operation was gastro-oesophageal reflux symptoms refractory to medical treatment.
      Twenty-one patients (81%) underwent a left thoracotomy, of whom 11 patients (42%)
      underwent a gastroplasty. The mean follow-up period was 8.27 years (range 1.5
      19.8 years), after which 14 patients (54%) were classified as Group A; 10
      patients (38%) as Group B; and 2 patients (8%) as Group C. Within Groups B and C,
      manometry showed that re-operation had increased basal lower oesophageal
      sphincter pressure (4.6 vs 12.7 mmHg, pre- vs post-operative P=0.03), and in all,
      but one case pH studies showed no evidence of recurrent acid reflux. CONCLUSIONS:
      Redo antireflux surgery can provide complete symptomatic relief in approximately
      50% of patients and symptomatic improvement over 90% of patients. We advocate a
      tailored approach in the selection of re-operative procedures based on the
      results of pre-operative oesophageal function testing.

PMID- 15519175
TI  - Complete mechanical cervical anastomosis using a narrow gastric tube after
      esophagectomy for cancer.
AB  - OBJECTIVE: Fibrous stenosis of the esophagogastric cervical anastomosis remains a
      significant complication occurring in up to one-third of cases. Trying to reduce
      the incidence of this complication, we describe our technique of cervical
      esophagogastric anastomosis using endoscopic linear stapler which seems to reduce
      the incidence of fibrous stricture formation after resection of esophageal
      cancer. METHODS: Between March 2000 and June 2003, 26 patients (15 males and 11
      females) underwent esophagectomy using tubulized stomach for reconstruction.
      Cervical esophagogastric anastomosis using linear endoscopic stapler was
      performed in all cases. The occurrence of post-operative anastomotic leak and
      development of anastomotic stricture were recorded and analyzed. RESULTS: All
      patients survived esophagectomy and were available for post-operative follow-up.
      Anastomotic leak developed in one case. No patient developed fibrous stenosis
      that required dilatation therapy. CONCLUSION: Complete mechanical esophagogastric
      anastomosis, using endoscopic linear stapler is effective and safe, even when a
      narrow gastric tube is used as esophageal substitute. This technique seems
      superior to other techniques to reduce the incidence of post-operative
      anastomotic complications.

PMID- 15519176
TI  - Spontaneous mediastinal emphysema.
AB  - OBJECTIVE: Spontaneous mediastinal emphysema is uncommon. Its cause has not been
      determined precisely, but the entity is usually associated with suddenly raised
      alveolar pressure. METHODS: Between 1980 and 2001, 114 patients with mediastinal
      emphysema of various causes were hospitalized in the Wolfson Medical Center. In
      22 of these patients (19.3%) the emphysema occurred without an obvious preceding
      event and was classified as spontaneous. The commonest symptoms and signs were
      chest pain, dyspnea and subcutaneous emphysema. All patients were kept under
      observation. Contrast esophagogram was performed in two patients who vomited.
      Pleural drains were inserted in six patients who had concomitant pneumothorax.
      RESULTS: All patients recovered and were followed for at least one year. There
      were no complications and no recurrences. CONCLUSIONS: Spontaneous mediastinal
      emphysema is usually a benign condition, which can be treated expectantly. The
      patients should be observed for 24 h. Recurrences are rare.

PMID- 15519177
TI  - Video-assisted thoracoscopic management of recurrent primary spontaneous
      pneumothorax after prior talc pleurodesis: a feasible, safe and efficient
      treatment option.
AB  - OBJECTIVE: To assess the role of video-assisted thoracoscopic surgery (VATS) in
      the management of a recurrent primary spontaneous pneumothorax after a prior talc
      pleurodesis. METHODS: From 1996 to 2002, we retrospectively reviewed all patients
      who were treated for a recurrent primary spontaneous pneumothorax after a
      previous talc pleurodesis. Data on the talc procedure and the recurrent
      pneumothorax, delay between both, and operative features were studied. Conversion
      rate to a thoracotomy and postoperative complications as well as long-term
      outcome were reported. RESULTS: We collected 39 patients (28 male) with a median
      age of 25 years (15-41 years). The initial procedure consisted of thoracoscopic
      talc poudrage in all cases. The median delay between the talc procedure and the
      recurrence was 23 months [10 days-13 years]. Size of recurrence involved 10-80%
      of the hemithorax. The VATS procedure was successfully achieved in 27 patients
      (69%) while 12 required conversion to a thoracotomy. The main cause for
      conversion was the presence of dense pleural adhesion at the mediastinal part of
      the pleural cavity. Postoperative morbidity was limited to pleural complications
      in the VATS group (n=6, 22%). Median follow-up was 26 months [10-38 months]. One
      patient treated by VATS developed a partial recurrent pneumothorax at 12 months
      with a favorable outcome without further surgery. CONCLUSIONS: Feasibility,
      safety and efficacy of VATS for management of recurrent primary spontaneous
      pneumothorax following thoracoscopic talc poudrage are strongly suggested.

PMID- 15519178
TI  - Video-assisted thoracic surgery for primary spontaneous hemopneumothorax.
AB  - OBJECTIVE: Video-assisted thoracic surgery (VATS) has changed the way we manage a
      number of thoracic conditions. This study presents near over a decade of
      experience from our institution on management of spontaneous hemopneumothorax
      (SHP), with particular reference to the use of VATS. METHODS: Retrospective
      review between March 1988 and December 2002 with 793 patients treated for
      spontaneous pneumothorax, 30 (3.8%) patients had SHP. The clinical features,
      indications for surgery and outcomes are discussed. RESULTS: All 30 SHP patients
      were male with mean age of 25 years. Signs of significant hypovolemia occurred in
      4 patients, 3 required blood transfusion. Mean initial blood drainage from tube
      thoracostomy was 594 ml. All SHP patients received surgery (5 thoracotomies, 25
      VATS). Active bleeding was identified in 16 patients; 12 from torn apical
      vascular adhesion band and 4 from vascular bleb. Postoperative complications
      after thoracotomy include 2 chest infections and 1 air leak, while VATS had 1
      chest infection and 1 air leak (P=0.022). Mean postoperative hospital stay
      following VATS was 3.9 days and thoracotomy 7.5 days (P=0.0021). There is no
      recurrence of pneumothorax or SHP during mean follow-up of 21 months. CONCLUSION:
      SHP can be life threatening and is a cause for patients presenting with
      unexplained signs of significant hypovolemia. Surgery in the form of VATS should
      be considered early in the management of SHP, with potentially less postoperative
      complications and shorter postoperative hospital stay compared with open
      thoracotomy.

PMID- 15519179
TI  - A prospective study of autologous 'blood patch' pleurodesis for persistent air
      leak after pulmonary resection.
AB  - OBJECTIVE: To evaluate the efficacy and risks of autologous 'blood patch'
      pleurodesis in patients with persistent air leak after pulmonary resection.
      METHODS: All patients operated on by a single surgeon between January 2002 and
      January 2004 and presenting with a persistent air leak after pulmonary resection
      have been treated by the autologous blood patch pleurodesis technique. Fifty
      millilitres of autologous blood were injected through the chest tube that was
      then rinsed, clamped for 30 min and then unclamped and placed back to water seal.
      RESULTS: We have obtained a 100% success rate in 11 patients with persistent air
      leak who have been treated with this technique over a 2-year period. Most air
      leaks (72.7%) ceased within 12 h of blood injection. No patient developed
      empyema, but two patients developed fever and pleural fluid grew Staphylococcus
      after blood pleurodesis. At 3-month follow-up, all patients were well and their
      lungs were expanded fully. CONCLUSIONS: In our experience a single injection of
      50 ml of blood is sufficient to seal persistent air leaks in less than 48 h.
      Although highly effective, the autologous blood patch pleurodesis technique
      should not be used in patients with incomplete lung re-expansion or positive
      pleural fluid culture to minimize the risk of empyema.

PMID- 15519180
TI  - Beta-blocking therapy in patients with the Marfan syndrome and entire aortic
      replacement.
AB  - OBJECTIVE: Beta-blocking therapy is the standard therapy in non-operated Marfan
      patients, however its efficacy after entire aortic replacement is unknown. The
      aim of this study was to describe the influence of (nearly) entire aortic
      replacement and beta-blocking therapy on blood pressure and wave reflections in
      Marfan patients. METHODS: Four Marfan patients (mean age 31+/-3 years) and 8 age
      matched control subjects were studied. Blood pressure and wave reflections
      (reflection coefficient and augmentation index) were studied by means of magnetic
      resonance imaging, continuous non-invasive blood pressure measurements and
      applanation tonometry. Patients were studied with atenolol, labetalol and without
      beta-blocking therapy. RESULTS: In Marfan patients, aortic systolic pressure
      (129+/-13 vs 114+/-10 mmHg), pulse pressure (58+/-13 vs 40+/-5 mmHg), wave speed
      (11+/-3 vs 4+/-0.4 m s(-1)) and reflection coefficient (65+/-22 vs 41+/-5%) were
      significantly increased compared to controls. There was no difference in aortic
      pressure between various medications in Marfan patients (atenolol 129/76 mmHg,
      labetalol 121/75 mmHg and without beta-blocking therapy 129/71 mmHg). Higher
      reflection coefficients were seen in patients with atenolol compared to
      discontinued medication (73+/-18 vs 65+/-22%), and also the augmentation index
      was higher with atenolol compared to labetalol and discontinued medication (24+/
      22 vs 17+/-17 vs 22+/-22%, respectively). CONCLUSION: Our results describe
      increased pulse pressure, systolic pressure, wave speed and wave reflections in
      four Marfan patients after entire aortic replacement. The use of atenolol or
      labetalol did not decrease aortic pressure and with atenolol increased wave
      reflections were observed. Therefore, the beneficial effect of atenolol in these
      patients is doubtful.

PMID- 15519181
TI  - Near-infrared spectroscopy for monitoring cerebral ischemia during selective
      cerebral perfusion.
AB  - OBJECTIVE: To minimize the neurological complications following cardiovascular
      surgery, it is essential to prevent an occurrence of cerebrovascular embolism and
      to detect and solve cerebral malperfusion without delay in the operating theater.
      Although we have introduced near-infrared spectroscopy (NIRS) monitoring for the
      purpose of detecting cerebral malperfusion, no criterion has been available. We
      searched for this criterion by examining the relationship of sustained drop in
      the regional oxygen saturation (rSO2) of the frontal lobes to the occurrence of
      neurological events. METHODS: The 59 consecutive patients undergoing aortic
      surgery with selective cerebral perfusion (SCP) were examined. The rSO2 was
      monitored throughout the surgery and the durations of drops in rSO2 to below 55%
      and those below 60% were determined for each patient. The durations of rSO2 drop
      and other surgery-related parameters were compared between the patients in whom
      neurological events occurred and those without such events. RESULTS: A total of
      16 cases (27.1%) presented with neurological events. Newly developed cerebral
      infarction was documented in 6 of these 16 cases. Operation time and the
      durations for which rSO2 dropped were significantly longer for the 16 patients
      with neurological events than for the 43 patients without events (Op time: 546.8
      versus 448.1 min, P=0.0064; rSO2 below 60%: 141.2 versus 49.8 min, P=0.0032; rSO2
      below 55%: 66.6 versus 10.6 min, P=0.0011), while there was no significant
      difference in age, bypass time, aortic clamping time, SCP time, and circulatory
      arrest time between the two groups. In the 3 patients with infarcts suggestive to
      hypoperfusion, sustained decrease in rSO2 was observed, while it was not
      significant in the remaining 3 patients with infarcts suggestive to embolism.
      Among the 53 patients without infarction, transient neurological events occurred
      more frequently in patients with sustained drop in rSO2 below 55% for over 5 min
      (44.4% versus 5.7%, P=0.0014). CONCLUSIONS: A sustained drop in rSO2 during
      aortic surgery is closely related to the occurrence of neurological events
      following surgery. We recommend that recovery of drop in rSO2 below 55% should be
      addressed without delay. However, use of NIRS is limited for detecting embolic
      events or hypoperfusion in the basilar region.

PMID- 15519182
TI  - Cerebral activation of mitogen-activated protein kinases after circulatory arrest
      and low flow cardiopulmonary bypass.
AB  - OBJECTIVES: Mitogen-activated protein kinases (MAPK) are important intermediates
      in the signal transduction pathways involved in neuronal dysfunction following
      cerebral ischemia-reperfusion injury. One subfamily, extracellular regulated
      kinase 1/2, has been heavily implicated in the pathogenesis of post-ischemic
      neuronal damage. However, the contribution of extracellular regulated kinase 1/2
      to neuronal damage following deep hypothermic circulatory arrest and low flow
      cardiopulmonary bypass is unknown. We attempted to correlate the extent of
      neuronal damage present following deep hypothermic circulatory arrest and low
      flow cardiopulmonary bypass with phosphorylated extracellular regulated kinase
      1/2 expression in the cerebral vascular endothelium. METHODS: Piglets underwent
      normal flow cardiopulmonary bypass (n=4) deep hypothermic circulatory arrest
      (n=6) and low flow cardiopulmonary bypass (n=5). Brains were harvested following
      24 h of post-cardiopulmonary bypass recovery. Cerebral cortical watershed zones,
      hippocampus, basal ganglia, thalamus, cerebellum, mesencephalon, pons and medulla
      were evaluated using hematoxylin and eosin staining. A section of ischemic cortex
      was evaluated by immunohistochemistry with rabbit polyclonal antibodies against
      phosphorylated extracellular regulated kinase 1/2. RESULTS: Compared to
      cardiopulmonary bypass controls, the deep hypothermic circulatory arrest and low
      flow cardiopulmonary bypass piglets exhibited diffuse ischemic changes with
      overlapping severity and distribution. Significant neuronal damage occurred in
      the frontal watershed zones and basal ganglia of the deep hypothermic circulatory
      arrest group (P<0.05). No detectable phosphorylated extracellular regulated
      kinase 1/2 immunoreactivity was found in the cardiopulmonary bypass controls;
      however, ERK 1/2 immunoreactivity was present in the cerebral vascular
      endothelium of the deep hypothermic circulatory arrest and low flow
      cardiopulmonary bypass groups. CONCLUSIONS: Our results indicate that
      phosphorylated extracellular regulated kinase 1/2 may play a prominent role in
      early cerebral ischemia-reperfusion injury and endothelial dysfunction. The
      pharmacologic inhibition of extracellular regulated kinase 1/2 represents a new
      and exciting opportunity for the modulation of cerebral tolerance to low flow
      cardiopulmonary bypass and deep hypothermic circulatory arrest.

PMID- 15519183
TI  - The short term effects of cardiopulmonary bypass on neurologic function in
      children and young adults.
AB  - OBJECTIVE: Cognitive deficits are common in adults following surgery utilizing
      cardiopulmonary bypass (CPB). A previous retrospective study suggested that
      surgical closure of an ASD in children was associated with neurologic injury,
      while transcather therapy was not. In a prospective study, we sought to determine
      whether neurologic deficits occur following repair of non-complex congenital
      heart lesions in school-age children and young adults. METHODS: Inclusion
      criteria were: age between 5 and 20 years, cardiac surgery utilizing CPB without
      deep hypothermic circulatory arrest, and no prior cardiac surgery. Patients
      underwent psychometric testing 1-3 days prior to surgery and re-evaluation 7-18
      days after surgery. In order to determine the test/re-test effect an age-matched
      cohort of children undergoing transcather closure of ASD under general anesthesia
      was also evaluated. The primary outcome measures were verbal and picture memory.
      Additional psychometric tests included: computerized performance test (CPT) and
      Digit Span (DS). Forty-one patients were enrolled, 29 undergoing surgery with CPB
      and 12 controls. Surgical procedures included ASD closure (n=13), VSD closure
      (n=10), resection of sub-aortic stenosis (n=3), mitral valvuloplasty (n=3). Mild
      hypothermia was used in all cases. The mean duration of CPB was 54+/-22 min.
      RESULTS: There was no significant difference in any of the psychometric test
      scores between subjects undergoing surgery with CPB or controls. CONCLUSIONS:
      There are no marked adverse neurologic effects of CPB in school-age children and
      young adults undergoing non-complex open-heart surgery. These data are important
      in counseling patients and families and should be considered in the debate as to
      the relative merits of transcather versus open-heart repair of various heart
      lesions.

PMID- 15519184
TI  - Reduced complement activation during cardiopulmonary bypass does not affect the
      postoperative acute phase response.
AB  - OBJECTIVE: In the present study the relationship was evaluated between
      perioperative inflammation and the postoperative acute phase response in patients
      undergoing elective coronary artery bypass grafting (CABG) assisted by
      cardiopulmonary bypass (CPB). CPB circuits contained either non-coated- (UMS),
      Carmeda- (BPS) or Trillium-coated oxygenators (BAS). METHODS: Prospectively, 71
      CABG patients were randomly allocated to one of the oxygenator groups (UMS: n=25,
      BPS: n=25 and BAS: n=21). Terminal complement complexes (TCC) and elastase were
      determined in plasma samples collected before, during and after bypass. Secretory
      phospholipase A2 (sPLA2) and C-reactive protein (CRP) were determined before and
      after bypass. RESULTS: Demographic, CPB and clinical outcome data were similar
      for the three groups. TCC and elastase increased during CPB, and decreased
      thereafter. Significant differences between the groups were present in the levels
      of TCC at the end of CPB (P=0.002) and at the first (P=0.012) and second
      (P<0.001) postoperative days, the BPS and BAS groups having reduced levels of TCC
      compared to the UMS group. Also elastase concentrations differed significantly
      between the groups at the end of CPB (P<0.001). The postoperative sPLA2 and CRP
      levels increased in all three groups on the first and second postoperative days,
      but no significant differences were present between the groups. CONCLUSIONS:
      Material-induced reduction of the inflammatory response during CPB does not
      affect the postoperative acute phase response. Thus, in CABG patients this
      response seems relatively unaffected by the composition and/or biocompatibility
      of the modern CPB circuit and rather to be evoked by surgical trauma, anesthetics
      and organ perfusion.

PMID- 15519185
TI  - The effect of methylprednisolone treatment on the cardiopulmonary bypass-induced
      systemic inflammatory response.
AB  - OBJECTIVE: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with
      an inflammatory response caused by contact of blood with artificial surfaces of
      the extracorporeal circuit, ischemia-reperfusion injury, and release of
      endotoxin. The inflammatory reaction involves activation of complement
      leucocytes, and endothelial cells with secretion of cytokines, proteases,
      arachidonic acid metabolites, and generation of oxygen derived free radicals
      (OFR) by polymorphonuclear neutrophils (PMN). Although this inflammatory response
      to CPB often remains at subclinical levels, it can also lead to major organ
      dysfunction. A number of studies have demonstrated that treatment of patients
      with a high-dose (30 mg/kg) of corticosteroids (methylprednisolone) attenuates
      the CPB-induced SIR and improves the outcome of patients undergoing cardiac
      surgery. However, large doses of steroids can cause abnormal metabolic responses
      such as metabolic acidosis and hyperglycemia. In the present study, we examined
      the efficacy of low doses of methylprednisolone (5 and 10 mg/kg) to attenuate the
      CPB-induced inflammatory response, during and after heart operations. METHODS:
      Thirty-six adult patients undergoing cardiac surgery, were randomized into three
      groups: (1) control group: group A; (2) methylprednisolone, 5 mg/kg body weight:
      group B; and (3) methylprednisolone, 10 mg/kg body weight: group C. Plasma levels
      of the cytokines interleukin-6 (IL-6) and TNF-alpha were analyzed by enzyme
      linked immunosorbent assay, before, during, and after CPB. OFR production was
      determined by cytofluorometry (FACS) at the same end points. RESULTS: No
      significant differences in age, body weight, CPB time, and cross-clamp time were
      observed among the three groups. CPB induced a marked increased in cytokine
      release and OFR generation. Low-dose of methylprednisolone (5 mg/kg) effectively
      reduced the increase in TNF-alpha and IL-6 secretion (P<0.05 compared to control
      group) after release of the cross-clamp. However, OFR generation was
      significantly reduced with a greater dose of methylprednisolone (10 mg/kg).
      CONCLUSIONS: The results indicate that a single low-dose of methylprednisolone
      (10 mg/kg) reduces the inflammatory reaction during and after CPB, by inhibition
      of proinflammatory cytokine release and OFR generation after release of the
      aortic cross-clamp.

PMID- 15519186
TI  - Red blood cell aggregation during cardiopulmonary bypass: a pathogenic cofactor
      in endothelial cell activation?
AB  - OBJECTIVE: The bio-incompatibility of the cardiopulmonary bypass (CPB) circuit
      and the use of artificial colloids trigger massive defense reaction that involves
      endothelial cells and several blood cells: platelets, neutrophils, monocytes, red
      blood cells (RBC) and lymphocytes. Investigating the effects on RBC aggregation
      and endothelial cells activation, the present study addresses two different prime
      solutions commonly used in the clinical practice. METHODS: RBC aggregation was
      measured by means of Laser-assisted Optical Rotation Cell Analyzer, in an in
      vitro study designed to mimic the human blood-material interactions during
      extracorporeal circulation. A clinical study investigating endothelial activation
      was conducted in 20 patients undergoing elective coronary bypass surgery,
      randomly assigned for CPB using two different priming solutions: HAES-steril 6%
      (HES 200/0.5) and Voluven 6% (HES 130/0.4). RESULTS: Circulation trough a
      Chandler loop of HES-blood mixes altered significantly RBC aggregability. The use
      of HES 130/0.4 resulted in marked decrease in RBC aggregation (aggregation index
      (AI) before and after circulation was 23.5+/-3.8 and 18+/-2.9, respectively), no
      significant differences being found when compared with Ringer's lactate group.
      The use of HES 200/0.5 resulted in better maintained RBC aggregation (AI 39.7+/
      5.9 and 29.7+/-4.7 before and after circulation, respectively). The AI measured
      for the whole blood (control) sample was 61.9+/-4.9 before circulation, and
      58.1+/-4 after. Markers of endothelial activation (von Willebrand factor (vWF),
      thrombomodulin (TM), tissue plasminogen activator (tPA) and E-selectin)
      significantly increased during CPB. Differences between HES treatment groups were
      evident post-bypass. While the markers of endothelial activation returned to
      baseline in HES 200/0.5 group, HES 130/0.4 was associated on the first post
      operative day with further increase of vWF and tPA. CONCLUSION: RBC aggregation
      significantly drooped as consequence of blood dilution and blood-material
      interaction. We reason that low RBC aggregation added to plasma viscosity
      reduction and non-physiologic flow conditions during extracorporeal circulation
      are important factors contributing to loss of shear stress at the venous
      endothelial wall. The loss of shear stress triggers complex signaling leading to
      endothelial activation. Additional fundamental research is needed in order to
      verify the hypothesis introduced by the present study. Characterizing the impact
      of rheologic parameters on endothelial function could prove to be valuable in
      patients undergoing CPB.

PMID- 15519187
TI  - How much heparin do we really need to go on pump? A rethink of current practices.
AB  - OBJECTIVES: Patients undergoing myocardial revascularisation using extracorporeal
      circulation require heparin anticoagulation. We aimed to evaluate the effect of
      reducing heparin dosage on target activated clotting time (ACT) and postoperative
      blood loss. METHODS: In a prospective randomised trial, 195 patients undergoing
      isolated primary CABG were randomised into four groups A, B, C, and D receiving
      an initial heparin dosage of 100, 200, 250 and 300 iu/kg, respectively. Extra
      incremental heparin (50 iu/kg) was added if required to achieve a target ACT of
      480 s before initiating cardiopulmonary bypass. Postoperative blood loss was
      measured from the time of heparin reversal to drain removal 24h later. RESULTS:
      Target ACT was achieved in 0, 63, 68.3 and 82.4% of patients in groups A, B, C
      and D, respectively, after the initial dose of heparin. In group B, of those not
      achieving target act a single increment of heparin was sufficient to achieve
      target ACT in further 18.6%. The mean ACT after the initial dose in groups B, C
      and D was 482.9, 519 and 588 s, respectively (P<0.05). Postoperative blood loss
      in millilitre per kilogram was directly proportional to preoperative heparin
      dose. CONCLUSIONS: Patients receiving lower dose of heparin has lower
      postoperative blood loss. Of those achieving the target ACT, group B was
      significantly the closest to the target ACT. A starting dose of 200 iu/kg of
      heparin and if necessary one 50 iu/kg increment achieved target ACT in 81.5% of
      patients. The added benefit of significant drop in postoperative blood loss is
      evident.

PMID- 15519188
TI  - Influence of low molecular weight heparin preparations on human internal thoracic
      artery contraction.
AB  - OBJECTIVE: Low molecular weight heparins (LMWHs) offer practical and potential
      pharmacological advantages over unfractionated heparin in multiple applications
      but have not been studied as vasoactive agents. The purpose of this study was to
      investigate the effects of two commercial preparations of LMWHs, enoxaparin
      sodium and nadroparin calcium, on vasoconstriction in the human internal thoracic
      artery (ITA) in vitro. METHODS: Samples of redundant ITA segments obtained from
      36 patients who underwent coronary artery bypass surgery were cut into 3mm wide
      rings and suspended in 20 ml organ bath. Activity of ITA rings precontracted with
      80 mM KCl, 0.1 microM endothelin-1 (ET-1) and 1 microM norepinephrine (NE) after
      administration of enoxaparin and nadroparin in accumulative concentration ranging
      from 0.1 to 13.2 UI AXa/ml were recorded under isometric conditions by means of
      force transducers with digital output. The contraction after 80 mmol KCl, 0.1
      microM ET-1 and 1 microM NE administration was treated as a control. RESULTS:
      Both studied LMWHs in concentration ranging from 0.12 to 13.2 UI AXa/ml did not
      change basal tonus and KCl precontracted ITA rings. When used in concentrations
      higher than 13.2 UI AXa/ml nadroparin but not enoxaparin significantly increased
      the tension in KCl precontracted arterial rings. In NE and ET-1 precontracted
      rings enoxaparin and nadroparin caused dose dependent relaxation without
      significant differences between both preparations. Incubation with nitric oxide
      blocker-Nomega-NITRO-L-ARGININE (L-NNA) in concentration 0.2 mM caused a
      significant attenuation of relaxant responses to both studied LMWHs in NE and ET
      1 precontracted rings. CONCLUSION: LMWHs can have vasorelaxant effects on the
      receptor-mediated ITA vasoconstriction. The results suggest that LMWHs-induced
      relaxation in the human ITA is at least partially caused by nitric oxide release.
      Although the vasoactive effects are not the primary advantage of these drugs used
      as antithrombotics, such effects might have some clinical importance in the
      treatment and prophylaxis of graft spasm.

PMID- 15519189
TI  - Reactivity of the human internal thoracic artery to vasodilators in coronary
      artery bypass grafting.
AB  - OBJECTIVE: The internal thoracic artery (ITA) is a useful conduit for coronary
      artery bypass grafting (CABG) and the patency rate is indispensable. Recently we
      have developed a method for increasing ITA blood flow during surgery by directly
      injecting phosphodiesterase III inhibitor (PDE III-I) into the left ITA (LITA) to
      prevent its contracture. In this study, we compared the reactivity of LITA blood
      flows before and after injection of four drugs: saline, papaverine hydrochloride,
      isosorbide dinitrate (ISDN), and PDE III-I. METHOD: 80 patients who were
      undergoing the first primary CABG, were randomly separated into four groups. Each
      group consisted of 20 patients. LITA graft free flow (GFF) and systemic mean
      blood pressure (MBP) were measured before and 1 min after direct intra LITA drug
      administration and blood vessel resistance (R) was calculated. RESULT: The saline
      group showed no significant changes in GFF, R value, and MBP. Significant
      increase in GFF was observed in the PDE III-I and ISDN groups. Except the saline
      group, each group exhibited a significant decrease in both the R value and MBP. A
      comparison of the change rate of MBP showed no significant differences among the
      four groups. The PDE III-I significantly increased the change rate of GFF and
      decreased the change rate of R value, when compared to the saline and papaverine
      hydrochloride groups. The PDE III-I showed a tendency to increase the change rate
      of GFF and to decrease the change rate of the R value compared to the ISDN group.
      CONCLUSION: The results of this study suggested that the PDE III-I is the most
      effective for increasing the blood flow of a LITA graft for CABG during surgery.

PMID- 15519190
TI  - Adenovirus-mediated overexpression of inhibitor kappa B-alpha attenuates
      postinfarct remodeling in the rat heart.
AB  - OBJECTIVE: The transcription factor nuclear factor kappa B (NF-kB) plays an
      important role in the inflammatory response following myocardial infarction. We
      hypothesized that NF-kB-blockade in an animal model of acute ischemia reduces the
      inflammatory response and therefore attenuates ventricular remodeling. METHODS:
      Myocardial infarcts (MI) were produced in male Sprague-Dawley rats by ligation of
      the LAD and followed by adenovirus-mediated intramyocardial delivery of inhibitor
      kappa Balpha-gene (n=10), the physiological inhibitor of the transcription factor
      nuclear factor kappa B, respectively, of a beta-gal reporter-gene (n=11). Sham
      operated animals (n=10) received neither ligation nor gene transfer. Five days
      after MI IkB-expression levels were determined by western blotting. Seven weeks
      after MI in vivo cardiac function was evaluated by transthoracic
      echocardiography. Based on left ventricular endsystolic and enddiastolic
      diameters ejection fraction and fractional shortening were calculated. Only
      animals with MI involving more than 30% of the left ventricle were included. Data
      are given as mean+/-SD. RESULTS: In IkBalpha-transfected hearts IkBalpha-levels
      were six-fold higher (P<0.05) than in beta-gal transfected hearts. Concerning in
      vivo hemodynamics IkBalpha-treated hearts showed reduced systolic and diastolic
      left ventricular dimensions compared to the beta-gal MI-group (systolic 48+/-4
      vs. 66+/-3 mm; diastolic 67+/-5 vs. 84+/-6 mm; P<0.01). Consequently fractional
      shortening (27.8+/-1.5 vs. 20.4+/-4.0%; P<0.01) and ejection fraction (63.4+/-3.6
      vs. 49.1+/-8.3%; P<0.05) were preserved in IkBalpha hearts compared to beta-gal
      MI-hearts. CONCLUSION: It can be concluded that overexpression of IkBalpha leads
      to an improved cardiac function thereby attenuating postinfarct remodeling.

PMID- 15519191
TI  - Myocardial protection by remote preconditioning: the role of nuclear factor kappa
      B p105 and inducible nitric oxide synthase.
AB  - OBJECTIVE: Adaptation to ischemia by brief episodes of ischemia and reperfusion
      (preconditioning) of the heart protects the heart against sustained ischemia,
      where the transcription factor nuclear factor kappa-B (NFkappaB) appears crucial
      for the protection. Preconditioning of the heart may even be evoked by brief
      episodes of ischemia and reperfusion in other organs. The present study
      investigates a possible role for NFkappaB and inducible nitric oxide synthase
      (iNOS) in adaption to ischemia by remote, delayed protection. METHODS: Mice (wild
      types, or with targeted deletions of the NFkappaB p105 or the iNOS gene) were
      subjected to cycles of occlusion and reperfusion of both hind limbs, and 24 h
      later their hearts were isolated and Langendorff-perfused with induced global
      ischemia and reperfusion. Infarct size was measured. Skeletal muscles from
      ischemized limbs as well as hearts were also collected for polymerase chain
      reaction (PCR) and electromobility shift assay (EMSA). RESULTS: Hind limb
      preconditioning protected left ventricular function and reduced infarct size
      during reperfusion in wild-type mice. Nuclear translocation of NFkappaB was
      detected in both heart and preconditioned skeletal muscle 1-2 h after the
      preconditioning episodes (EMSA); while cardiac mRNA for iNOS gradually increased
      in a 24-h time course after hind limb preconditioning (real-time PCR). When hind
      limbs of mice with targeted deletions for the p105 subunit of NFkappaB or the
      iNOS gene were preconditioned, no beneficial effect was observed in the heart.
      CONCLUSIONS: Delayed cardioprotection induced by hind limb preconditioning
      involves signaling through NFkappaB and iNOS.

PMID- 15519192
TI  - Myocardial protective effect of FR167653; a novel cytokine inhibitor in ischemic
      reperfused rat heart.
AB  - OBJECTIVES: In this study, a newly synthesized cytokine inhibitor FR167653 was
      investigated using a rat heart ischemia-reperfusion model to prove its myocardial
      protective effect and its role in the inhibition of cytokine production in
      ischemic myocardium. METHODS: Studies were performed with isolated, Langendorff
      perfused Lewis rat hearts (n=80) which were either treated with FR167653 or
      untreated, as the control group, and subjected to ischemia-reperfusion. RESULTS:
      Reperfusion followed by 30min of 37 degrees C ischemia induced marked myocardial
      cytokine expression and activated p38MAPK. FR167653 administered before ischemia
      and during reperfusion significantly reduced ischemia-activated myocardial
      TNFalpha mRNA expression (190+/-97 vs. 4805+/-3017, P=0.024) as well as TNFalpha
      production (0 vs. 9.6+/-2.5 ng/ml, P<0.05) and also inhibited p38 MAPK
      activation. Its administration improved recovery of cardiac contractile function
      during reperfusion: LVDP (130+/-18 vs. 82+/-21 mmHg (P=0.002)), max/min dP/dt
      (2812+/-328/-2283+/-216 vs. 1520+/-424/-1325+/-237 mmHg/s, P=0.003). CPK leakage
      was significantly reduced in FR167653 treated hearts versus untreated hearts
      (54+/-6 vs. 0.5+/-0.1, P<0.05) and reduction of coronary flow was improved (110+/
      13 vs. 77+/-11%) 1h after beginning of reperfusion (P<0.05). Moreover, FR
      administration attenuated the number of TUNEL positive cardiomyocytes (3+/-1 vs.
      9+/-2%). CONCLUSION: These data demonstrated positive inotropic and antiapoptotic
      effects of a newly synthesized compound (FR167653) of cytokine inhibitors and its
      inhibitory effect on myocardial TNFalpha production and p38 MAPK activation in
      ischemic-reperfused rat heart. This suggested that cytokine inhibition is
      significant as a method for myocardial protection against ischemia-reperfusion
      injury.

PMID- 15519193
TI  - Enhancement of Na+,K(+)-ATPase and Ca(2+)-ATPase activities in multi-cycle
      ischemic preconditioning in rabbit hearts.
AB  - OBJECTIVE: Ischemic preconditioning (IP) has been shown to attenuate
      intracellular Na+ accumulation and Ca2+ overload during ischemia and reperfusion,
      both of which are closely related to the outcome of myocardial damage. We
      compared the effects of single- and four-cycle IP in Na+,K(+)-activated adenosine
      5'-triphosphatase (Na+,K(+)-ATPase) and Ca(2+)-activated adenosine 5'
      triphosphatase (Ca(2+)-ATPase) activities in in vivo rabbit hearts, correlating
      these differences to the quality of protection against subsequent ischemia.
      METHODS: The morphological outcome was evaluated in in vivo rabbit hearts
      subjected to 30 min of coronary occlusion and reperfusion for 180 min by
      assessing the ratio of infarct volume to risk zone volume. The effects of single-
      and four-cycle preconditioning ischemia were then examined. Another set of in
      vivo rabbit hearts was subjected to the measurement of ATPase activities at the
      conclusion of final preconditioning ischemia and at 60 min after reperfusion
      following 30 min of ischemia. RESULTS: The infarct volume was reduced by single
      cycle IP to 38% of that in the control group. The four-cycle IP further reduced
      the infarct volume, which was 11% of that in the control group. Na+,K(+)-ATPase
      activity at 60 min after reperfusion in the four-cycle group was increased to
      172% of that in the control group (10.8 micromol ADP/h/mg protein), whereas no
      difference was found in the single-cycle group. On the other hand, Ca(2+)-ATPase
      activity at the conclusion of IP was increased by single-cycle IP, the value
      being 255% of that in the control group (4.9 micromol ADP/h/mg protein). The four
      cycle IP further increased the activity, and the value was 158% of that in the
      single-cycle group. CONCLUSIONS: Since increases in Na+,K(+)-ATPase and Ca(2+)
      ATPase activities contribute to the decrease in intracellular Ca2+ concentration,
      the enhancement of these activities by four-cycle IP may be involved in the
      additional protection.

PMID- 15519194
TI  - Duration of action of antispasmodic agents: novel use of a mouse model as an in
      vivo pharmacological assay.
AB  - OBJECTIVE: Radial arteries are increasingly used as conduits for coronary artery
      bypass grafts, but perioperative graft vasospasm remains a concern. In vitro
      testing has demonstrated the efficacy of phenoxybenzamine and
      verapamil/nitroglycerin as topical antispasmodic agents, but their duration of
      action in vivo is unknown. Using an in vivo mouse model, we measured their
      duration of action in functioning vascular grafts, and compared this to their in
      vitro duration of action in ungrafted vascular segments. METHODS: Two millimetre
      mouse aortic segments (C57/BL6) were incubated with phenoxybenzamine,
      verapamil/nitroglycerin, or buffer (controls) for 15 min in organ chambers.
      Isometric tension responses to phenylephrine and prostaglandin F2alpha were
      measured at 0, 2, 6 and 12 h post-incubation. In parallel, 36 murine infrarenal
      aortic interposition grafts (2 mm) were performed. Twelve grafts were pre-treated
      (15 min) with phenoxybenzamine, 12 with verapamil/nitroglycerin and 12 remained
      untreated (controls). Isometric tension responses to the same agonists were
      measured in grafts harvested 2, 6, 13 and 23 h after surgery. RESULTS:
      Phenoxybenzamine prevented alpha-adrenergic vasoconstriction for up to 16 h in
      vivo (grafts), and 12h in vitro (ungrafted segments). Verapamil/nitroglycerin was
      effective for at least 2 h in vitro, but did not prevent vasoconstriction after 2
      h in vivo. CONCLUSIONS: The mouse model appears to be a useful technique for
      assessing the pharmacological properties of antispasmodic agents in vivo.
      Phenoxybenzamine has an extended action in arterial grafts in vivo.
      Verapamil/nitroglycerin is short-lived in vivo but lasts longer in vitro.
      Measurements of antispasmodic duration of action in vitro should be interpreted
      with caution.

PMID- 15519195
TI  - Non-viral in vivo thrombomodulin gene transfer prevents early loss of
      thromboresistance of grafted veins.
AB  - OBJECTIVE: Immediate loss of thrombomodulin activity in the endothelium of vein
      grafts has been demonstrated during 90 min exposure to arterial circulation; this
      loss of activity is ascribed as an important cause of early thrombosis.
      Conventional ex vivo gene transfection after vein harvest cannot cover this acute
      period immediately after implantation. We have established a highly efficient non
      viral gene therapy protocol utilizing modified transferrin receptor-facilitated
      gene transfer. Using this technique, we examined whether in vivo thrombomodulin
      gene therapy, directed to the endothelium of rat veins 2 days prior to grafting,
      may prevent thromboresistance impairment of vein grafts under simulated arterial
      circulation. METHODS: Abdomen of SD rat was opened and cationic
      liposome:transferrin:thrombomodulin gene complexes or the vector without DNAs
      were applied to the inferior vena cava of rats while blood flow was reduced by
      proximal and distal clamping. After 2 days, the transfected veins were harvested
      and thrombomodulin expression and thromboresistance properties determined before
      and after exposure to an artificial circuit. RESULTS: The trial of gene
      transfection using variable doses of DNAs confirmed that 7.5 microg of total DNAs
      was the most efficient quantity for thrombomodulin gene transfection to IVCs,
      although accompanying an increase of gene expression in other downstream organs.
      By transfection of the thrombomodulin gene in IVCs, the generation capacity of
      activated protein C in venous endothelium increased three-fold compared with
      veins treated with vector alone (P<0.01). Under simulated arterial circulation,
      perfusion of veins treated with vector alone decreased thrombomodulin activity to
      36% of preperfused levels (P<0.01), whereas transfected grafts preserved the
      activity at normal vein endothelium levels even after perfusion. Consequently,
      the increase in endothelial thrombin activity induced by simulated arterial
      circulation was markedly attenuated in transfected veins (P<0.01), while
      immunohistochemistry confirmed the preservation of endothelial lining.
      CONCLUSIONS: Transferrin receptor-facilitated in vivo gene transfer to the
      inferior vena cava resulted in sufficient thrombomodulin gene expression
      immediately after graft implantation and subsequent maintenance of
      thromboresistance even after exposure to arterial pressure. Although further
      studies are needed, the present results suggest the possibility of gene therapy
      targeting acute phases of vein graft disease.

PMID- 15519196
TI  - Vasomotor dysfunction after cardiac surgery.
AB  - Cardiopulmonary bypass and cardioplegic arrest, which allow for support of the
      circulation and stabilization of the heart during cardiac procedures, are still
      used for the vast majority of cardiac operations worldwide. However, in addition
      to a well-recognized systemic inflammatory response, cardiopulmonary bypass and
      cardioplegic arrest elicit complex, multifactorial vasomotor disturbances that
      vary according to the affected organ bed, with reduced vascular resistances in
      the skeletal muscle and peripheral circulation, and increased propensity to spasm
      in the cardiac, pulmonary, mesenteric and cerebral vascular beds. This article
      outlines the nature, mechanistic basis, and clinical correlates of the vasomotor
      alterations encountered in patients undergoing cardiac surgery using
      cardiopulmonary bypass and cardioplegic arrest.

PMID- 15519197
TI  - Are wound healing disturbances and length of hospital stay reduced with minimally
      invasive vein harvest? A meta-analysis.
AB  - Minimally invasive great saphenous vein harvest for coronary artery bypass
      grafting aims to reduce post-operative leg-wound related morbidity. In a meta
      analysis of randomised trials we have shown leg wound infection rates to be
      significantly lower in patients undergoing minimally invasive harvest. This study
      aims to use meta-analysis to compare the two techniques with regards to non
      infective wound healing disturbances (NIWHD) (wound drainage, haematoma,
      dehiscence, necrosis, need for surgical debridement, and seroma formation). A
      meta-analysis of all studies published between 1995 and 2002 reporting a
      comparison between the two techniques was performed. Primary outcomes of interest
      were the six wound healing disturbances mentioned above and length of hospital
      stay. Heterogeneity was assessed using graphical exploration and sensitivity
      analysis with subgroup analysis. Twenty-seven studies published between 1997 and
      2002 matched our selection criteria, with a combined total of 4953 subjects, of
      which 2442(49%) underwent minimally invasive harvest and 2511(51%) underwent
      conventional surgery. When considering only randomised studies, the total number
      of non-infective wound disturbances was lower in minimally invasive (4%) as
      compared to the conventional (13%) group (random effect OR 0.24, CI 0.16-0.38).
      Similar results were found when only fully matched studies were considered. The
      absolute risk reduction when comparing the two techniques was calculated to be
      0.10, which translates to a number of patients needed to treat of 10. Length of
      stay was significantly reduced in the minimally invasive group in comparison to
      the conventional group (random effect weighted mean difference of -1.04, CI -1.92
      to -0.16). Our results suggest that NIWHD all reduced with minimally invasive
      harvest techniques. Despite the limitations of this meta-analysis, we feel we
      have once again illustrated an important link between minimally invasive great
      saphenous vein harvest and improved tissue healing when compared to conventional
      open surgery. This has the potential to reduce wound-related morbidity,
      infection, post-operative pain, length of hospital stay, and re-admission rate.

PMID- 15519198
TI  - Early hemofiltration improves survival in post-cardiotomy patients with acute
      renal failure.
AB  - OBJECTIVE: The application and timing of hemofiltration (continuous veno-venous
      hemofiltration, CVVH) in patients with acute renal failure (ARF) post cardiac
      surgery has been called into question because of uncertain short-term outcome.
      The aim of the present study was to identify how the timing of introduction of
      hemofiltration affects the morbidity and mortality in patients with ARF after
      cardiac surgery. METHODS: 1264 consecutive patients who underwent adult cardiac
      surgical procedures performed between January 2002 and January 2003 were audited.
      Out of these, case notes of 64 patients who required renal supportive
      intervention were reviewed. Statistical significance was accepted at a level of
      P<0.05. RESULTS: Of the 64 (5%) patients, who developed ARF and required CVVH,
      there were 48 males and 16 females. Mean age was 70+/-6.8 years. The hospital
      mortality was 43% (12 patients) in Group-I and 22% (8) in Group-II (P<0.05),
      giving an overall 1.5% mortality associated with ARF. The mean time between the
      operation and the initiation of CVVH was 2.55+/-2.2 days in Group-I and 0.78+/
      0.2 days in Group-II (P<0.001). The mean duration of CVVH was 4.57+/-11.4 days in
      Group-I and 4.61+/-2.0 days in Group-II (P=NS). Older age (P=0.013), elevated
      preoperative creatinine (P=0.002), postoperative pulmonary oedema (P=0.01),
      sepsis (P=0.001), multiple organ failure (P=0.031), hypotension (P=0.031) and
      preoperative renal failure (P<0.05) were the independent factors influencing the
      poor postoperative outcome and cardiac instability. CONCLUSION: Early and
      aggressive use of CVVH is associated with better than expected survival in severe
      ARF after cardiac operations.

PMID- 15519199
TI  - Computer tools to assist the monitoring of outcomes in surgery.
AB  - OBJECTIVE: In recent years, there has been increasing use of analytical and
      graphical methods to assist the monitoring of outcomes in adult cardiac surgery.
      In this paper, we present extensions to the basic VLAD methodology that add
      flexibility and assist in its interpretation. METHODS: Using techniques from
      probability theory, we have devised graphical tools whereby deviations from
      expected outcomes can be monitored to see how likely they are to have occurred by
      chance. The methods are based upon pre-operative assessments of risk and use
      exact analytical techniques. RESULTS: These tools allow deviations from expected
      outcomes to be readily assessed and compared with the distribution of chance
      outcomes. Appropriate colour coding allows interpretation in terms of a
      temperature gradient. CONCLUSIONS: Exact analysis methods based on the use of pre
      operative risk assessment provide a useful means for assisting the interpretation
      of VLAD charts. Such analysis has the advantage that it is applicable even for
      relatively short series of operations. Also, it takes specific account of the
      heterogeneity of case mix when quantifying the variability that is expected. By
      displaying the overall history of outcomes in a visually intuitive manner, it
      complements the more formal tools for detecting isolated good and bad runs that
      are available.

PMID- 15519200
TI  - Computed tomography angiographic demonstration of a ventricular septal defect.

PMID- 15519201
TI  - Intramuscular lipoma in the chest wall.

PMID- 15519203
TI  - Myxoma of the anterior leaflet of the mitral valve presenting with stroke in a
      young male.

PMID- 15519202
TI  - A penetrative cardiac injury by craftsmen meat hook.

PMID- 15519204
TI  - Azygos lobe small cell carcinoma.

PMID- 15519205
TI  - Unusual chronic rheumatoid empyema, presenting as a chest wall mass.

PMID- 15519206
TI  - Pneumopericardium--complication of an unknown tuberculosis in a HIV positive
      patient.

PMID- 15519207
TI  - Use of muscular VSD Amplatzer occluder for closing right ventricular free wall
      perforation after hybrid procedure.
AB  - In some patients, so cold hybrid cardiologic procedures are performed whereas a
      heart is exposed surgically to puncture directly the heart cavity. After
      performing the interventional procedure, the opening in ventricular wall is
      closed surgically. We present our initial experience with closing the right
      ventricular (RV) cavity opening with the muscular ventricular septal defect
      Amplatzer occluder (A-MVSDO). In four sheep, heart was exposed surgically and
      punctured under direct vision by needle and guide wire, 14F and 26F sheath were
      introduced into right ventricle and the A-MVSDO was introduced causing closure of
      the RV opening. In all four cases, the occluder was successfully placed closing
      the opening in RV. No major bleeding after occlusion was observed. Following
      complications were observed: pneumothorax in two animals, rhythm disturbances and
      thrombus suspected in one. A-MVSDO occluder seems to be a useful device to close
      RV opening after hybrid interventional cardiologic procedure.

PMID- 15519208
TI  - A combined small cell carcinoma of the lung containing three components: small
      cell, spindle cell and squamous cell carcinoma.
AB  - A 61-year-old man was referred to our hospital because of rapid growth of a mass
      shadow revealed by chest radiography. The mass was diagnosed as pure small cell
      carcinoma by CT-guided needle biopsy, and the patient underwent chemotherapy.
      However, as the tumor showed no response, we considered the possibility of some
      other form of malignancy and performed surgery. Postoperatively, the mass was
      diagnosed as small cell carcinoma combined with small cell, spindle cell and
      squamous cell carcinoma. We report this case in view of the rarity of this
      combination of morphologic patterns in a primary bronchogenic carcinoma.

PMID- 15519209
TI  - Use of extracorporeal membrane oxygenation (ECMO) during whole lung lavage in
      pulmonary alveolar proteinosis associated with lung cancer.
AB  - We describe a case of pulmonary alveolar proteinosis in a male adult with lung
      cancer. To achieve the successful operation of lung cancer, we used percutaneous
      veno-venous extracorporeal membrane oxygenation (ECMO) during whole lung lavage
      (WLL) of the contralateral lung. We performed successful WLL under ECMO support.

PMID- 15519210
TI  - Hypoplastic left heart syndrome in situs inversus totalis.
AB  - A very rare case of a newborn with hypoplastic left heart syndrome and situs
      inversus totalis is herein reported. Successful surgical treatment of this
      cardiac malformation was accomplished at our institution and consisted of:
      modified Norwood stage I procedure, with direct anastomosis of the transected
      main pulmonary artery to the aortic arch, without any prosthetic material
      interposition and right ventricle to pulmonary artery polytetrafluoroethylene
      shunt.

PMID- 15519211
TI  - The implications of 'Haute Couture' on coronary blood flow: the bulk of
      hypothesis.

PMID- 15519212
TI  - Leaflet arrest in St Jude and CarboMedics valves: an experimental study.

PMID- 15519215
TI  - Paroxysmal nocturnal hemoglobinuria--pre- and perioperative rationale during
      cardiac surgery using extracorporeal circulation.

PMID- 15519218
TI  - Stents and sensibility--use of the Montgomery T-tube in tracheal stenosis.

PMID- 15519219
TI  - Mechanism of [M + H]+ formation in photoionization mass spectrometry.
AB  - In this paper we examine the mechanism of [M + H]+ (henceforth MH+) formation by
      direct photoionization. Based on comparisons of the relative abundance of M+ and
      MH+ ions for photoionization of a variety of compounds M as vapor in air versus
      in different solvents, we conclude that the mechanism is M + hnu --> M+ + e-
      followed by the reaction M+ + S --> MH+ + S(-H). The principal evidence for
      molecular radical ion formation M+ followed by hydrogen atom abstraction from
      protic solvent S are: (1) Nearly exclusive formation of M+ for headspace
      ionization of M in air, (2) significant relative abundance of MH+ in the presence
      of protic solvents (e.g., CH3OH, H2O, c-hexane), but not in aprotic solvents
      (e.g., CCl4-), (3) observation of induced equilibrium oscillations in the
      abundance of MH+ and M+, and (4) correlation of the ratio of MH+/M+ to reaction
      length in the photoionization source. Thermodynamic models are advanced that
      explain the qualitative dependence of the MH+/M+ equilibrium ratio on the
      properties of solvent S and analyte M. Though the hydrogen abstraction reaction
      is endothermic in most cases, it is shown that the equilibrium constant is still
      expected to be much greater than unity in most of the cases studied due to the
      very slow reverse reaction involving the very low abundant MH+ and S(-H) species.

PMID- 15519220
TI  - Competing fragmentation processes in tandem mass spectra of heparin-like
      glycosaminoglycans.
AB  - Heparin-like glycosaminoglycans (HLGAGs) are highly sulfated, linear
      carbohydrates attached to proteoglycan core proteins and expressed on cell
      surfaces and in basement membranes. These carbohydrates bind several families of
      growth factors and growth factor receptors and act as coreceptors for these
      molecules. Tandem mass spectrometry has the potential to increase our
      understanding of the biological significance of HLGAG expression by providing a
      facile means for sequencing these molecules without the need for time-consuming
      total purification. The challenge for tandem mass spectrometric analysis of
      HLGAGs is to produce abundant ions derived via glycosidic bond cleavages while
      minimizing the abundances of ions produced from elimination of the fragile
      sulfate groups. This work describes the competing fragmentation pathways that
      result from dissociation of high negative charge state ions generated from
      HLGAGs. Glycosidic bond cleavage ion formation competes with losses of
      equivalents of H2SO4, resulting in complex ion patterns. For the most highly
      sulfated structure examined, an octasulfated tetramer, an unusual loss of charge
      from the precursor ion was observed, accompanied by low abundance ions
      originating from subsequent backbone cleavages. These results demonstrate that
      fragmentation processes competing with glycosidic bond cleavages are more favored
      for highly sulfated HLGAG ions. In conclusion, reduction of charge-charge
      repulsions, such as is achieved by pairing the HLGAG ions with metal cations, is
      necessary in order to minimize the abundances of ions derived via fragmentation
      processes that compete with glycosidic bond cleavages.

PMID- 15519221
TI  - Characterization of glycopeptides from HIV-I(SF2) gp120 by liquid chromatography
      mass spectrometry.
AB  - Previously, we have characterized the HIV-I(SF2) gp120 glycopeptides using matrix
      assisted laser desorption/ionization mass spectrometry (MALDI/MS) and nanospray
      electrospray ionization (ESI). Although we characterized 25 of 26 consensus
      glycosylation sites, we could not obtain any information about the extent of
      sialylation of the complex glycans. Sialylation is known to alter the biological
      activity of some glycoproteins, e.g., infectivity of some human and nonhuman
      primate lentiviruses is reduced when the envelope glycoproteins are extensively
      sialylated, and thus, characterization of the extent of sialylation of complex
      glycoproteins is of biological interest. Since neither MALDI/MS nor nanospray ESI
      provided much information about sialylation, probably because of suppression
      effects inherent in these techniques, we utilized online nanocapillary high
      performance liquid chromatography (nHPLC) with ESI/MS to characterize the sites
      and extent of sialylation on gp120. Eight of the known 26 consensus glycosylation
      sites of HIV-ISF2 gp120 were determined to be sialylated. Two of these sites were
      previously uncharacterized complex glycans. Thirteen high mannose sites were also
      determined. The heterogeneity of four of these sites had not been previously
      characterized. In addition, a peptide containing two consensus glycosylation
      sites, which had previously been determined to contain complex glycans, was also
      determined to be high mannose as well.

PMID- 15519222
TI  - Folding analysis of hormonal polypeptide calcitonins and the oxidized calcitonins
      using electrospray ionization mass spectrometry combined with H/D exchange.
AB  - Conformational change of calcitonins has been examined by measuring the rate of
      hydrogen/deuterium (H/D) exchange in amino acids. Time dependent m/z shift caused
      by H/D exchange was monitored by electrospray ionization quadrupole ion trap mass
      spectrometry (ESI-QIT MS). The rate constants of H/D exchange were calculated
      from apparent first-order kinetics. The time course of H/D exchange exhibited two
      phases of faster and slower exchange. The smaller rate constant (k2) estimated
      from the slower H/D exchange was correlated with an alpha-helix content that
      reflected the folding state. The order of k2 values obtained for human calcitonin
      (hCT), porcine calcitonin (pCT), salmon calcitonin (sCT), and elcatonin (ECT) was
      hCT > pCT approximately sCT > ECT. Although the amino acid sequence of sCT is
      similar to that of ECT, their k2 values were considerably different. The results
      suggest that ECT is relatively rigid on the N-terminal side cyclic structure in
      the folded state. Further, the effect of methionine oxidation on k2 has been
      examined. In the oxidized pCT that possesses similar biological activity with the
      intact pCT, the k2 values obtained were nearly equal. The k2 of hCT increased via
      methionine oxidation, and the biological activity was weakened by oxidation. This
      suggested that methionine oxidation of hCT produced unfolding in the secondary
      structure and that oxidative unfolding of hCT led to the loss of biological
      activity. The results indicate that the H/D exchange rate constant may be used as
      an informative parameter to elucidate the relationship between the folded state
      and biological activity of polypeptides like calcitonins with secondary
      structure.

PMID- 15519223
TI  - Tandem mass spectrometry for the determination of the sites of DNA interstrand
      cross-link.
AB  - Formation of DNA interstrand cross-link is implicated in the mechanism of
      anticancer activity of some drugs. Here we examined the fragmentation of
      deprotonated ions of double-stranded oligodeoxynucleotides (ODNs) that are
      covalently held together with either a mitomycin C or a 4,5',8-trimethylpsoralen.
      Our results showed that, upon collisional activation, the covalently-bound duplex
      ODNs cleaved to give a series of wn and [an-base] ions; the sites of interstrand
      cross-linking could be determined from the mass shifts of some product ions. In
      addition, compared with the product-ion spectra acquired on an ion trap, those
      obtained from sustained off-resonance irradiation-collisionally activated
      dissociation (SORI-CAD) on a Fourier transform mass spectrometer offered high
      mass-resolving power, which facilitated unambiguous assignment of product ions
      and made it an effective method for locating the cross-linking sites.

PMID- 15519224
TI  - Transport of 13C-oleate in adipocytes measured using multi imaging mass
      spectrometry.
AB  - The mechanism of long chain free fatty acid (FFA) transport across cell membranes
      is under active investigation. Here we describe the use of multi imaging mass
      spectrometry (MIMS) to monitor intracellular concentrations of FFA and provide
      new insight into FFA transport in cultured adipocytes. Cells were incubated with
      13C-oleate:BSA and either dried directly or dried after washing with a medium
      deprived of 13C-oleate:BSA. Cells were analyzed with MIMS using a scanning
      primary Cs+ ion beam and 12C-, 13C-, 12C14N-, 13C14N-) (or 12C 15N-) were imaged
      simultaneously. From these quantitative images the values of the 13C/ 12C ratios
      were determined in the intracellular lipid droplets, in the cytoplasm and outside
      the 3T3F442A adipocytes. The results indicate that after incubation with 13C
      oleate:BSA the droplet 13C/ 12C ratio was 15 +/- 6%. This value is about 14-fold
      higher than the 13C/ 12C terrestrial ratio (1.12%). After washing the 13C
      oleate:BSA, the droplet 13C/ 12C ratios decreased to 1.6 +/- 0.1%, about 40%
      greater than the natural abundance. Results for washed cells indicate that
      relatively little FFA was esterified. The unwashed cell results, together with
      the value of the lipid water partition coefficient, reveal that intracellular
      unbound FFA (FFAu) concentrations were on average about 4.5-fold greater than the
      extracellular FFAu concentrations. These results are consistent with the
      possibility that FFA may be pumped into adipocytes against their electro-chemical
      potential. This work demonstrates that MIMS can be used to image and quantitate
      stable isotope labeled fatty acid in intracellular lipid droplets.

PMID- 15519225
TI  - Infrared multiphoton dissociation (IRMPD) and collisionally activated
      dissociation of peptides in a quadrupole ion trap with selective IRMPD of
      phosphopeptides.
AB  - Dissociation of protonated peptides via infrared multiphoton dissociation (IRMPD)
      provides more extensive sequence information than is obtained with collisionally
      activated dissociation (CAD) in a quadrupole ion trap due to the lack of the CAD
      low m/z cutoff and the ability to form secondary and higher order fragments with
      the non-resonant photoactivation technique. In addition, IRMPD is shown to be
      useful for the selective dissociation of phosphopeptides over those which are not
      phosphorylated because the greater photon absorption efficiency of the
      phosphorylated peptides leads to their more rapid dissociation. Finally, the
      selectivity of the IRMPD technique for phosphorylated species in complex mixtures
      is confirmed with the analysis of a mock peptide mixture and a tryptic digest of
      alpha-casein.

PMID- 15519226
TI  - Evaluation of complexes of DNA duplexes and novel benzoxazoles or benzimidazoles
      by electrospray ionization mass spectrometry.
AB  - Electrospray ionization mass spectrometry is used to compare the metal ion
      binding and metal-mediated DNA binding of benzoxazole (1, 2, 3, 4) and
      benzimidazole (5) compounds and to elucidate the putative binding modes and
      stoichiometries. The observed metal versus non-metal-mediated DNA binding, as
      well as the specificity of DNA binding, is correlated with the biological
      activities of the analogs. The ESI-MS spectra for the antibacterial benzoxazole
      and benzimidazole analogs 4 and 5 demonstrated non-specific and non-metal
      mediated binding to DNA, with the appearance of DNA complexes containing multiple
      ligands. The anticancer analog 2 demonstrates a clear preference for metal
      mediated DNA interactions, with an apparent selectivity for Ni2+ -mediated
      binding over the more physiologically relevant Mg2+ or Zn2+ cations. Complexation
      between DNA and the biologically inactive analog 1 was not observed, either in
      the absence or presence of metal cations.

PMID- 15519227
TI  - Strategy for selective chemical cross-linking of tyrosine and lysine residues.
AB  - Chemical cross-linking of proteins combined with mass spectral analysis is a
      powerful technique that can be utilized to yield protein structural information,
      such as the spatial arrangement of multi-protein complexes or the folding of
      monomeric proteins. The succinimidyl ester cross-linking reagents are commonly
      used to cross-link primary amine-containing amino acids (N-terminus and lysine).
      However, in this study they were used to react with tyrosines as well, which
      allowed for the formation of cross-links between two primary amines, one primary
      amine and one tyrosine, or two tyrosines. This result is extremely important to
      the chemical cross-linking community for two reasons: (1) all possible cross
      linked residues must be considered when analyzing data from these experiments to
      generate correct distance constraints and structural information, and (2)
      utilizing the versatility of these cross-linking reagents allows more information
      content to be generated from a single cross-linking reagent, which may increase
      the number of cross-links obtained in the experiment. Herein, we study the
      reactivity of the succinimidyl ester labeling and cross-linking reagents with
      angiotensin I and oxidized insulin beta-chain. Using the succinimidyl acetate
      labeling reagent, the reactivity of the N-terminus was found to be greater than
      either lysine or tyrosine. However, a selectivity of the cross-linking reagent
      was observed for either tyrosine or lysine depending on the pH of the reaction
      solution. In acidic pH, it was observed that tyrosine was more reactive, while in
      alkaline pH lysine was more reactive. Exploiting this selectivity predominantly N
      terminus-tyrosine or tyrosine-tyrosine cross-links were favored at acidic pH,
      while N-terminus-tyrosine or tyrosine-lysine cross-links were favored at alkaline
      pH.

PMID- 15519228
TI  - Using amino acids for probing structural information of cytochrome c by
      electrospray ionization mass spectrometry.
AB  - By using electrospray ionization mass spectrometry (ESI-MS), protein complexes of
      cytochrome c with amino acids were studied. Different amino acids were
      investigated to explore these complexes. Using these amino acids, a strategy for
      probing the structure of cytochrome c was established. It was found that L-Arg
      and L-Glu could bind with cytochrome c to form noncovalent complexes. At low pH
      solution, complexes between the cytochrome c molecule with several L-Arg
      molecules (multiple L-Arg adducts) were formed, and the number of binding ligands
      depended on the charge state of cytochrome c. While in neutral solution, the
      cytochrome c molecule complexed with only one L-Arg molecule (single L-Arg
      adducts). As for L-Glu, only single L-Glu adducts were formed in both acidic and
      neutral solutions.

PMID- 15519229
TI  - Collisional activation of ions in RF ion traps and ion guides: the effective ion
      temperature treatment.
AB  - Ion transfer and storage using inhomogeneous radio frequency (RF) electric fields
      in combination with gas-assisted ion cooling and focusing constitutes one of the
      basic techniques in mass spectrometry today. The RF motion of ions in the bath
      gas environment involves a large number of ion-neutral collisions that leads to
      the internal activation of ions and their effective "heating" (when a thermal
      distribution of internal energies results). The degree of ion activation required
      in various applications may range from a minimum level (e.g., slightly raising
      the average internal energy) to an intense level resulting in ion fragmentation.
      Several research groups proposed using the effective temperature as a measure of
      ion activation under conditions of multiple ion-neutral collisions. Here we
      present approximate relationships for the effective ion temperature relevant to
      typical operation modes of RF multipole devices. We show that RF ion activation
      results in near-thermal energies for ions occupying an equilibrium position at
      the center of an RF trap, whereas increased ion activation can be produced by
      shifting ions off-center, e.g., by means of an external DC electric field. The
      ion dissociation in the linear quadrupole ion trap using the dipolar DC ion
      activation has been observed experimentally and interpreted in terms of the
      effective ion temperature.

PMID- 15519230
TI  - Carbon nanotubes as affinity probes for peptides and proteins in MALDI MS
      analysis.
AB  - Recently, carbon nanotubes (CNTs) have been reported to be an effective MALDI
      matrix for small molecules (Anal. Chem.2003, 75, 6191). In a somewhat related
      study, we have employed CNTs produced by using NaH-treated anodic aluminum oxide
      (Na@AAO) as a reactive template as the assisting matrix for MALDI analysis upon
      the addition of high concentrations of citrate buffer. Our results indicate that
      the mass range can be extended to ca. 12,000 Da and that alkali metal adducts of
      analytes are effectively reduced. Furthermore, we have employed citric acid
      treated CNTs as affinity probes to selectively concentrate traces of analytes
      from aqueous solutions. High concentrations of salts and surfactants in the
      sample solutions are also tolerated. This approach is very suitable for the MALDI
      analysis of small proteins, peptides, and protein enzymatic digest products.

PMID- 15519231
TI  - Tandem mass spectrometric investigation of acylpolyamines of spider venoms and
      their 15N-labeled derivatives.
AB  - The fragmentation mechanism of the acylpentamine toxins 1-4 found in the venom of
      the spider Agelenopsis aperta has been investigated in detail. To identify the
      origin of the two doublets of unexpected fragment ions at m/z 129/112 and m/z
      115/98, three synthetic 15N-labeled analogs 5-7 have been prepared and subjected
      to CID fragmentation on a triple quadrupole mass spectrometer. It appears that
      the unexpected doublet of fragment ions arises from an internal portion of the
      polyamine backbone after either a transaminative Zip reaction or a sequential
      fragmentation of the quasi-molecular ion. The second option has been proven by in
      source CID experiments. The detailed knowledge of acylpentamine fragmentation
      mechanisms is essential for the correct characterization of isomeric compounds,
      particularly for coeluting compounds within complex mixtures such as spider
      venoms.

PMID- 15519232
TI  - Forensic confirmatory analysis of ethyl sulfate--a new marker for alcohol
      consumption--by liquid-chromatography/electrospray ionization/tandem mass
      spectrometry.
AB  - Ethyl sulfate (EtS)--a new direct marker for ethanol intake besides ethyl
      glucuronide (EtG) and others--was detected in urine samples by electrospray
      ionization tandem mass-spectrometry (LC-ESI-MS/MS). Ethyl sulfate sodium salt was
      used for method development, yielding a precursor [M - H]- m/z 125 and product
      ions m/z 97 [HSO4]- and m/z 80 [SO3]-. Pentadeuterated EtS (D5-EtS) was
      synthesized by esterification of sulfuric acid with anhydrous hexadeutero ethanol
      ([M - H]- m/z 130, product ions m/z 98 [DSO4]- and m/z 80 [SO3]-). After addition
      of D5-EtS and D5-EtG, urine samples were analyzed by direct injection into the
      gradient LC-MS/MS system. Analysis was performed in accordance with forensic
      guidelines for confirmatory analysis using one precursor and two product ions.
      EtS has been detected (in addition to EtG) in the urine samples of nine
      volunteers after drinking sparkling wine containing between 9 and 49 g of
      ethanol. Both EtS and EtG could be detected up to 36 h after consumption of
      alcohol. The excretion profile was found to be similar to that of EtG. No EtS was
      found in teetotalers' urine samples. Method validation parameters are presented.
      EtS was stable in urine upon storage up to twenty days at room temperature. In
      addition to EtG, EtS can be used to detect recent alcohol consumption, thus
      providing a second marker for the time range of up to approximately one day after
      elimination of ethanol from urine samples. The determination of EtS can be used
      in addition to EtG as proof of ethanol consumption in workplace monitoring
      programs.

PMID- 15519233
TI  - Fully-automated chip-based nanoelectrospray tandem mass spectrometry of
      gangliosides from human cerebellum.
AB  - The introduction of chip-based electrospray (ESI) ion sources into biological
      mass spectrometry (MS) addressed the fundamental issue of how to analyze minute
      amounts of complex biological systems. The automation of sample delivery into the
      MS combined with the chip-based ESI allows for high quality bioanalysis in a high
      throughput fashion. These advantages have already been demonstrated in
      proteomics, direct screening of drugs and drug discovery. As part of our
      continuing effort to implement automated chip-based mass spectrometry into the
      field of complex carbohydrate analysis, we hereby report the development of a
      chipESI MS and MS/MS methodology for the screening of gangliosides. A strategy to
      characterize a complex ganglioside mixture from human cerebellar tissue, by
      automated ESIchip-quadrupole time-of-flight (QTOF) MS and MS/MS is presented
      here. The feasibility of this method, and the general experimental requirements
      for automated chipESI MS analysis of these carbohydrate species is described.

PMID- 15519234
TI  - Indirect detection of protein-metal binding: interaction of serum transferrin
      with In3+ and Bi3+.
AB  - Transferrins comprise a class of monomeric glycoproteins found in all
      vertebrates, whose function is iron sequestration and transport. In addition to
      iron, serum transferrin also binds a variety of other metals and is believed to
      provide a route for the in vivo delivery of such metals to cells. In the present
      study, ESI MS is used to investigate interactions between human serum transferrin
      and two nonferrous metals, indium (a commonly used imaging agent) and bismuth (a
      component of many antiulcer drugs). While the UV-Vis absorption spectroscopy
      measurements clearly indicate that both metals bind strongly to transferrin in
      solution, the metal-protein complex can be detected by ESI MS only for indium,
      but not for bismuth. Despite the apparently low stability of the transferrin
      bismuth complex in the gas phase, presence of such complex in solution can be
      established by ESI MS indirectly. This is done by monitoring the evolution of
      charge state distributions of transferrin ions upon acid-induced protein
      unfolding in the presence and in the absence of the metal in solution. The
      anomalous instability of the transferrin-bismuth complex in the gas phase is
      rationalized in terms of conformational differences between this form of
      transferrin and the holo-forms of this protein produced by binding of metals with
      smaller ionic radii (e.g., Fe3+ and In3+). The large size of Bi3+ ion is likely
      to prevent formation of a closed conformation (canonical structure of the holo
      protein), resulting in a non-native metal coordination. It is suggested that
      transferrin retains the open conformation (characteristic of the apo-form) upon
      binding Bi3+, with only two ligands in the metal coordination sphere provided by
      the protein itself. This suggestion is corroborated by the results of circular
      dichroism measurements in the near-UV range. Since the cellular consumption of
      metals in the transferrin cycle critically depends upon recognition of the holo
      protein complex by the transferrin receptor, the noncanonical conformation of the
      transferrin-bismuth complex may explain very inefficient delivery of bismuth to
      cells even when a high dosage of bismuth-containing drugs is administered for
      prolonged periods of time.

PMID- 15519235
TI  - Strategies and data analysis techniques for lipid and phospholipid chemistry
      elucidation by intact cell MALDI-FTMS.
AB  - Ions attributed to lipids and phospholipids are directly observed by desorption
      from whole bacteria using intact cell (IC) matrix-assisted laser desorption
      ionization (MALDI) Fourier transform mass spectrometry (FTMS). Saccharomyces
      cerevisiae are grown in rich media broth, concentrated, and applied directly to
      the MALDI surface without lysis or chemical treatment. FTMS of MALDI ions gives
      excellent signal to noise ratios with typical resolving powers of 90,000 and mass
      precision better than 0.002 Da. Use of accurate mass measurements and a simple
      set of rules allow assignment of major peaks into one of twelve expected lipid
      classes. Subsequently, fractional mass versus whole number mass plots are
      employed to enhance visual interpretation of the high-resolution data and to
      facilitate detection of related ions such as those representing homologous series
      or different degrees of unsaturation. This approach, coupled with rules based on
      bacterial biochemistry, is used to classify ions with m/z up to about 1000. Major
      spectral peaks in the range m/z 200-1000 are assigned as lipids and
      phospholipids. In this study, it is assumed that biologically-derived ions with
      m/z values lower than 1000 are lipids. This is not unreasonable in view of the
      facts that molecular weights of lipids are almost always less than 1000 Da, that
      the copy numbers for lipids in a cell are higher than those for any single
      protein or other component, and that lipids are generally collections of distinct
      homologous partners, unlike proteins or other cell components. This paper
      presents a new rapid lipid-profiling method based on IC MALDI-FTMS.

PMID- 15519236
TI  - Generation of arylnitrenium ions by nitro-reduction and gas-phase synthesis of N
      heterocycles.
AB  - Nitro-reduction by the vinyl halide radical cation CH2 = CH-X+* (X = Cl or Br)
      converts nitroaromatics into arylnitrenium ions, significant intermediates in
      carcinogenesis, and the present study reports on the scope and regioselectivity
      of this versatile reaction. The reaction is general for different kinds of
      substituted nitroaromatics; para/meta substitutents have little effect on the
      reaction while ortho substitutents result in low yields of arylnitrenium ions.
      The phenylnitrenium ion PhNH+ can be generated by chemical ionization (CI) of
      nitrobenzene using 1,2-dichloroethane as the reagent gas or by atmospheric
      pressure chemical ionization (APCI) of 1,2-dichloroethane solution doped with
      nitrobenzene. The chemical reactivities of the arylnitrenium ions include one
      step ion/molecule reactions with nucleophiles ethyl vinyl ether and 1,3
      dioxolanes, respectively, involving the direct formation of new CN bonds and
      synthesis of indole and benzomorpholine derivatives. The indole formation
      reaction parallels known condensed phase chemistry, while the concise morpholine
      forming reaction remains to be sought in solution. The combination of collision
      induced dissociation (CID) with novel ion/molecule reactions should provide a
      selective method for the detection of explosives such as TNT, RDX and HMX in
      mixtures using mass spectrometry. In addition to the reduction of the nitro
      group, reduction of methyl phenyl sulfone PhS(O)2Me to the thioanisole radical
      cation PhSMe+* occurs using the same chemical ionization reagent 1,2
      dichloroethane. This probably involves an analogous reduction reaction by the
      reagent ion CH2 = CH-Cl+*.

PMID- 15519237
TI  - Long-term NR2B expression in the cerebellum alters granule cell development and
      leads to NR2A down-regulation and motor deficits.
AB  - N-methyl-D-aspartate receptor (NMDAR) composition in granule cells changes
      characteristically during cerebellar development. To analyze the importance of
      NR2B replacement by NR2C and NR2A subunits until the end of the first month of
      age, we generated mice with lasting NR2B expression but deficiency for NR2C (NR2C
      2B mice). Mutant phenotype was different from NR2C knock-out mice as loss of
      granule cells and morphological changes in NR2C/2B cerebellar architecture were
      already evident from the second postnatal week. Increased NR2B subunit levels led
      also to a gradual down-regulation of cerebellar NR2A levels, preceding the
      development of motor impairment in adult animals. Therefore, cerebellar NR2A is
      important for proper motor coordination and cannot be replaced by long-term
      expression of NR2B. Consequently, the physiological exchange of NMDA receptor
      subunits during cerebellar granule cell maturation is important for accurate
      postnatal development and function.

PMID- 15519238
TI  - Synaptic targeting of neuroligin is independent of neurexin and SAP90/PSD95
      binding.
AB  - Synaptic cell adhesion and synaptogenesis are thought to involve the interaction
      of neuroligin, a postsynaptic transmembrane protein, with its presynaptic ligand
      neurexin. Neuroligin also interacts with SAP90/PSD95, a multidomain scaffolding
      protein thought to recruit proteins to postsynaptic sites. Using expression of
      GFP-tagged versions of neuroligin in cultured hippocampal neurons, we find that
      neuroligin is targeted to synapses via intracellular sequences distinct from its
      SAP90/PSD95 binding site. A neuroligin mutant lacking the intracellular domain
      fails to target to synapses. These data indicate that postsynaptic targeting of
      neuroligin does not rely on the scaffolding action of SAP90/PSD95 and is not
      induced by binding to presynaptic neurexin. Neuroligin is rather targeted to
      synapses via a postsynaptic mechanism, which may precede and be necessary for
      subsequent recruitment of neurexin and other neuroligin interactors such as
      SAP90/PSD95, suggesting a pivotal position for neuroligin in a putative hierarchy
      of interactions assembling or stabilizing synapses.

PMID- 15519239
TI  - Dimerization of Parkinson's disease-causing DJ-1 and formation of high molecular
      weight complexes in human brain.
AB  - Mutations in the DJ-1 gene have been implicated in the PARK7-linked autosomal
      recessive form of Parkinson's disease (PD). The molecular properties of DJ-1WT,
      DJ-1L166P, and a newly identified disease-causing mutant DJ-1M26I were explored
      after they were transiently expressed in mammalian cells. Treatment of intact,
      living cells with the chemical crosslinker disuccinimidyl suberate (DSS) revealed
      that DJ-1WT and mutant DJ-1M26I were present as stable homodimers; DJ-1L166P in
      particular tended to form high-order complexes as well. In contrast to DJ-1L166P
      that is quickly degraded by the proteasome, DJ-1M26I was found to be an
      efficiently expressed and stable variant of DJ-1, suggesting that these mutations
      have distinct biochemical effects on DJ-1. We further provide evidence that in
      human brain, under nondenaturing conditions, DJ-1 is present in high molecular
      weight (HMW) complexes of approximately 250-700 kDa containing parkin, another PD
      associated protein.

PMID- 15519240
TI  - Increased expression of Nkx2.2 and Olig2 identifies reactive oligodendrocyte
      progenitor cells responding to demyelination in the adult CNS.
AB  - Within the adult CNS, a quiescent population of oligodendrocyte progenitor cells
      (OPCs) become activated in response to demyelination and give rise to
      remyelinating oligodendrocytes. During development, OPC differentiation is
      controlled by several transcription factors including Olig1 and Olig2, and
      Nkx2.2. We hypothesized that these genes may serve similar functions in activated
      adult OPCs allowing them to become remyelinating oligodendrocytes and tested this
      hypothesis by examining their expression during the remyelination of a toxin
      induced rodent model of demyelination. During the acute phase of demyelination,
      OPCs within the lesion increased their expression of Nkx2.2 and Olig2, two
      transcription factors that in combination are critical for oligodendrocyte
      differentiation during developmental myelination. This activation was not
      associated with increases in Sonic hedgehog (Shh) expression, which does not
      appear essential for CNS remyelination. Consistent with a role in the activation
      and differentiation of OPCs, these increases were delayed in old adult animals
      where the rate of remyelination is slowed. Our data suggest the hypothesis that
      increased expression of Nkx2.2 and Olig2 plays a critically important role in the
      differentiation of adult OPCs into remyelinating oligodendrocytes and that these
      genes may present novel targets for therapeutic manipulation in cases where
      remyelination is impaired.

PMID- 15519241
TI  - LIF receptor signaling modulates neural stem cell renewal.
AB  - Activation of the leukemia inhibitory factor (LIF) receptor has been reported to
      promote gliogenesis and also to support neural stem cell (NSC) renewal. To
      investigate this paradox, we isolated NSCs and generated neurospheres from
      embryonic mice either wild-type, heterozygous, or homozygous null for LIF
      receptor (LIFR)-beta. Exogenous LIF abrogated neurosphere formation and promoted
      expression of GFAP by all cells in wild-type and heterozygous cultures. LIF also
      stimulated a twofold increase in the number of multipotential clones generated
      from these cultures in comparison with those pretreated with EGF and FGF-2 (E+F)
      alone. In contrast, the clonogenicity of low-density cultures of LIFR knockout
      cells was reduced in comparison with that of wild-type cells grown in E+F and was
      unaffected by LIF. Thus, although LIFR signaling is not necessary for NSC self
      renewal, it enhances both the clonogenicity and the expression of GFAP by these
      multipotential cells.

PMID- 15519242
TI  - Inhibition of c-Jun phosphorylation reduces axonal outgrowth of adult rat nodose
      ganglia and dorsal root ganglia sensory neurons.
AB  - The role of c-Jun activation for survival and regeneration of sensory neurons is
      unclear. Here we report that c-Jun N-terminal kinase (JNK)-mediated c-Jun
      activation is important for axonal outgrowth of sensory neurons in rat nodose and
      dorsal root ganglia (DRG). Peripheral severance of the vagus or the sciatic nerve
      resulted in a massive and rapid, but transient increase of the activated JNK (p
      JNK) in neuronal nuclei, followed by c-Jun phosphorylation and activating
      transcription factor-3 (ATF3) induction. JNK inhibition by the selective JNK
      inhibitors SP600125 and (D)-JNKI1 did not affect neuronal survival in explanted
      or dissociated ganglia, but dramatically reduced axonal outgrowth, c-Jun
      activation, and ATF3 induction. Using retrograde labeling, we demonstrated that
      activated c-Jun (p-c-Jun) and ATF3 were associated with regenerative neurons.
      Taken together, our results suggest that JNK-mediated c-Jun activation is one of
      the first cell body reactions in response to nerve injury and that this
      activation and subsequent ATF3 induction are associated with axonal outgrowth.

PMID- 15519243
TI  - A single brain-derived neurotrophic factor injection modifies hypothalamo
      pituitary-adrenocortical axis activity in adult male rats.
AB  - Immobilization stress induces in adult male rats rapid activation of brain
      derived neurotrophic factor (BDNF) expression in the hypothalamic paraventricular
      nucleus (PVN) preceding the increases in corticotropin releasing hormone (CRH)
      and arginin-vasopressin (AVP) expression. The BDNF mRNA signal belatedly co
      localizes with CRH and AVP mRNA signals in the PVN, as determined by in situ
      hybridization. Intracerebroventricular BDNF injections (5 microg/rat) in non
      anesthetized adult male rats induce a gradual increase in the CRH mRNA signal
      whereas AVP mRNA signal progressively decreases in the parvocellular and
      magnocellular PVN portions. At the same time, the CRH hypothalamic content
      decreases while the AVP content increases. These variations are accompanied by
      increases in ACTH and corticosterone plasma concentrations. These results
      strongly suggest that BDNF could be a stress-responsive intercellular messenger
      since when it is exogenously administered acts as an important and early
      component in the activation and recruitment of hypothalamic CRH and AVP neurons.

PMID- 15519244
TI  - Astrocyte activation and dysfunction and neuron death by HIV-1 Tat expression in
      astrocytes.
AB  - Human immunodeficiency virus type 1 (HIV-1) Tat protein plays an important role
      in HIV-associated neuropathogenesis. Astrocytosis and neuron death are two
      hallmarks of HIV-1 infection of the central nervous system (CNS). However,
      whether there is a direct link between Tat expression, astrocytosis and
      subsequent neuron death is not known. In this study, we expressed Tat in
      astrocytes and examined Tat effects on astrocyte function and subsequent neuronal
      survival. The results showed that Tat expression resulted in a significant
      increase in glial fibrillary acidic protein (GFAP) expression, a cellular marker
      of astrocyte activation or astrocytosis. The GFAP promoter-driven reporter gene
      assay showed that Tat transactivated GFAP expression at the transcriptional
      level. Furthermore, Tat expression markedly impaired glutamate uptake by
      astrocytes. Importantly, cell culture supernatants from Tat-expressing astrocytes
      induced dramatic neuron death. Taken together, these data provide evidence for
      the first time to directly link Tat expression in astrocytes to astrocytosis,
      astrocyte dysfunction, and subsequent neuron death. In addition, these data
      suggest that astrocyte dysfunction contributes, at least in part, to Tat
      neurotoxicity and subsequently HIV-associated neuropathogenesis.

PMID- 15519245
TI  - MECP2 is progressively expressed in post-migratory neurons and is involved in
      neuronal maturation rather than cell fate decisions.
AB  - Rett syndrome is a neurodevelopmental disorder and one of the causes of mental
      retardation and autistic behavior in girls, as well as in a small group of boys.
      It was recently discovered that mutation of the methyl-CpG-binding protein 2
      (MECP2) gene encoding a transcriptional repressor on the X chromosome causes Rett
      syndrome. Although it is evident that phenotypes of MECP2 mutant mice that
      resemble those of Rett syndrome are attributable to lack of the MECP2 gene in the
      central nervous system (CNS), there is little understanding of the
      neuropathological abnormalities in the CNS of MECP2-null mice. Here, we
      investigated the developmental regulation and specific cellular expression of
      MECP2 during neural development both in vitro and in vivo. MECP2 is expressed in
      mature neurons, but not in astroglia or oligodendroglia, and is increasingly
      expressed during development of the mouse neocortex. In addition, in vitro
      culture studies suggest that MECP2 is expressed in more differentiated neurons
      rather than in less differentiated neuroblasts. Under in vitro conditions using
      neural precursor cultures, we find that MECP2 mutant neural precursors
      differentiate into morphologically mature neurons and glia, and no significant
      differences in differentiation are detected between cells from wild-type and
      MECP2 mutant mice, suggesting that MECP2 may play a different role in mice than
      it does in Xenopus embryos. In agreement with this hypothesis, neocortical
      projection layers in MECP2 -/y mice are thinner than those in wild-type mice, and
      pyramidal neurons in layer II/III in MECP2 -/y mice are smaller and less complex
      than those in wild-type mice. Taken together, our results indicate that MECP2 is
      involved in the maturation and maintenance of neurons, including dendritic
      arborization, rather than in cell fate decisions.

PMID- 15519246
TI  - Neural stem cells protect against glutamate-induced excitotoxicity and promote
      survival of injured motor neurons through the secretion of neurotrophic factors.
AB  - Besides their capacity to give rise to neurons and/or glia, neural stem cells
      (NSCs) appear to inherently secrete neurotrophic factors beneficial to injured
      neurons. To test this potential, we have implanted NSCs onto or adjacent to
      spinal cord cultures. When NSCs were placed adjacent to the spinal cord sections,
      motor neuron axons grew toward the NSCs. Furthermore, conditioned medium from
      NSCs cultures was also able to induce similar axonal outgrowth, suggesting that
      these NSCs secrete soluble factors that have tropic and/or trophic properties.
      ELISA revealed that the NSCs secrete glial cell-line-derived factor (GDNF) and
      nerve growth factor (NGF). Interestingly, preincubation of the conditioned medium
      with GDNF-blocking antibodies abolished axonal outgrowth. We also showed that
      NSCs can protect spinal cord cultures from experimentally induced excitotoxic
      damage. The neuroprotective potential of NSCs was further confirmed in vivo by
      their ability to protect against motor neuron cell death.

PMID- 15519247
TI  - SoxB transcription factors specify neuroectodermal lineage choice in ES cells.
AB  - Knowledge of lineage decision machinery in pluripotent embryonic stem (ES) cells
      may shed light on the process of germ layer segregation in the mammalian embryo
      and enable directed differentiation in vitro for biomedical applications. We have
      investigated the contribution of Class B1 Sox transcription factors to lineage
      choice during ES cell differentiation. We report that forced expression of Sox1
      or Sox2 did not impair propagation of undifferentiated ES cells, but upon release
      from self-renewal promoted differentiation into neuroectoderm at the expense of
      mesoderm and endoderm. The efficient specification of a primary lineage by
      transcription factor manipulation provides a paradigm for instructing
      differentiation of ES cells for biopharmaceutical screening and cell therapy
      applications.

PMID- 15519248
TI  - Bone metabolism in relation to alterations in systemic growth hormone.
AB  - Growth hormone (GH) has a major role in the maintenance of bone mass in adults by
      regulating bone remodeling through a complex interaction of circulating GH,
      insulin-like growth factors (IGFs), IGF binding protein (IGFBPs), and locally
      produced IGFs and IGFBPs, acting in an autocrine and paracrine way. In vitro data
      has greatly increased our understanding of GH and IGFs effects and regulation in
      bone cells under controlled conditions, and especially the molecular pathways
      involved. However, the GH-and type I IGF-receptor are present in many tissues and
      various systemic factors may potentially regulate local expression of IGFs and
      IGFBPs in the intact organism. The use of genetically altered mice has changed
      this and had a major impact on defining the role of IGFs in skeletal homeostasis,
      and especially the role of systemic IGF-I in the development and maintenance of
      the adult skeleton. The focus of this review is to describe recent work on the
      effect of GH/IGF on remodeling in the adult skeleton emphasizing on data obtained
      in patient populations (i.e. acromegaly, GH deficiency, postmenopausal
      osteoporosis) and experimental models (i.e. animals with genetically altered
      expression of different GH and IGF family members) characterized by different
      systemic levels of these proteins. The role of IGF-I as a coupling agent between
      resorption and bone formation through effects on osteoprotegerin (OPG) and
      receptor activator of NFkappaB ligand (RANKL) are also discussed.

PMID- 15519249
TI  - The physiological and pathophysiological roles of the GH/IGF-axis in the kidney:
      lessons from experimental rodent models.
AB  - The growth hormone (GH)/insulin-like growth factor (IGF) system plays an
      important role in renal development, growth, function and pathophysiology. IGF-I
      has been associated with renal/glomerular hypertrophy and compensatory renal
      growth. Potential effects on glomerular size are of interest, since an increase
      in glomerular size may be permissive for the development of glomerulosclerosis.
      In an effort to abolish the decline of renal function and possibly to restore the
      renal structure, different approaches have been tested in experimental models of
      nephropathy, focusing mainly on early renal changes. The involvement of the
      GH/IGF system in renal pathophysiology has been studied in much detail in the
      rat. In view of the growing interest in murine physiology, occurring in large
      part by genetically modified animals, this review examines those aspects of GH,
      IGFs, their receptors and binding proteins that relate both to mouse kidney
      physiology and to a number of conditions characterized by pathophysiological
      renal changes. A deeper understanding of the role of the GH/IGF system in renal
      dysfunction may stimulate the development of novel therapeutic approaches aiming
      at preventing or retarding various kidney diseases.

PMID- 15519250
TI  - Mini-review: estrogen action in the uterus and insulin-like growth factor-I.

PMID- 15519251
TI  - Insulin-like growth factor I levels during growth hormone (GH) replacement in GH
      deficient adults: a gender difference.
AB  - To evaluate the variation of serum IGF-1 levels during GH replacement and observe
      gender differences, 29 adults with GH deficiency (mean age 42.5 +/- 10.1 year),
      were studied. Serum IGF-1 was assessed every 4 weeks during the titration period
      and afterwards every 3 months of GH therapy. At baseline 77.7% of women and 45.4%
      of men had serum baseline IGF-1 levels below the lower limit of normal age
      related reference range. The time to reach the maintenance dose was lower in men
      than women (p < 0.05). There was an increase in IGF-1 levels after one year of GH
      therapy, significant only in men (p < 0.01). IGF-1 concentrations were higher in
      men than women (p < 0.05), at the 12th and 18th months of GH therapy. GH dose was
      reduced by 25% in men (p < 0.01). At the end of the study the mean GH dose was
      lower in men than in women (p < 0.05). The factor responsible for these findings
      is not known, however a possible role of androgens has been suggested.

PMID- 15519252
TI  - Pituitary hormone deficiencies due to transcription factor gene alterations.
AB  - Mechanisms that control pituitary development are gradually better understood.
      They involve molecular signals from surrounding structures and the expression of
      a cascade of homeodomain transcription factors. Mutations of these transcription
      factors cause defects of embryologic development of the anterior pituitary
      responsible for isolated or multiple pituitary hormone deficiencies
      (respectively, IPHD and MPHD) in both rodents and humans. In this review we
      emphasize the description of human phenotypes associated with genetic alterations
      found in IPHD (e.g. isolated corticotroph deficiency and Tpit mutations) and MPHD
      (mutations of POU1F1, PROP1, Hesx1, Lhx3, Lhx4, Ptx2).

PMID- 15519253
TI  - Serum adiponectin levels in adult growth hormone deficiency and acromegaly.
AB  - Atherosclerosis and insulin resistance are common complications of adult growth
      hormone deficiency (GHD) and acromegaly. Circulating adiponectin, an adipocyte
      derived protein, has both anti-atherogenic and insulin-sensitising effects. In
      this study, we measured serum adiponectin levels in patients with either adult
      GHD or acromegaly to clarify the impact of GH secretory states on the regulation
      of serum adiponectin levels. Serum adiponectin level was measured by
      radioimmunoassay in 32 patients with adult GHD, 49 patients with acromegaly and
      25 normal subjects. The relationships between adiponectin and insulin sensitivity
      index assessed as quantitative insulin sensitivity check index (QUICKI), BMI, and
      serum GH and IGF-I levels were then investigated. The values of QUICKI were
      significantly lower in patients with acromegaly or adult GHD compared to normal
      subjects (0.33 +/- 0.03, P < 0.01, 0.35 +/- 0.04, P < 0.05 and 0.36 +/- 0.01,
      respectively). While patients with adult GHD had significantly lower serum
      adiponectin levels than patients with acromegaly (6.5 +/- 3.9, 9.2 +/- 5.0, P <
      0.01) these levels were not significantly different from those found in normal
      subjects (7.8 +/- 4.3 mug/ml). There was an inverse correlation between serum
      adiponectin levels and BMI in both patient groups (GHD r = -0.39, P < 0.05;
      Acromegaly r = -0.35, P < 0.05). However, serum adiponectin levels correlated
      positively with QUICKI (R(s) = 0.37, P < 0.05) only in patients with adult GHD.
      In patients with acromegaly, the levels of circulating adiponectin showed an
      inverse correlation with serum IGF-I levels (R(s) = -0.34, P < 0.05), but not
      with basal GH levels. These results demonstrate that adiponectin levels are
      significantly lower in patients with adult GHD than in patients with acromegaly.
      Adiponectin levels are similar in patients with GHD and healthy controls, whereas
      in patients with acromegaly, insulin resistance appears to be not closely related
      to adiponectin levels compared with BMI. The different relationship between
      adiponectin and QUICKI observed in the adult GHD and acromegaly groups presumably
      reflects differences in the mechanisms of insulin resistance under states of GH
      deficiency or excess.

PMID- 15519254
TI  - Spontaneous growth hormone secretion and IGF1:IGFBP3 molar ratios in children
      born small for gestational age (SGA).
AB  - OBJECTIVE: To analyze spontaneous nocturnal GH profiles, IGF1 and IGFBP3 serum
      levels, as well as IGF1:IGFBP3 molar ratios in SGA children without postnatal
      catch-up growth. METHODS: Short statured prepubertal SGA children (n = 24) were
      matched retrospectively for sex, age and BMI to short statured children born
      appropriate for gestational age (AGA), who underwent the same diagnostic program.
      GH deficiency was excluded in all children by a normal increase of GH in 2
      stimulation tests (>8 microg/L). For assessment of spontaneous nocturnal GH
      secretion, GH serum levels were measured every 20 min for 10 h. Pulsatility was
      analyzed with Pulsar. RESULTS: None of the Pulsar derived descriptive parameters
      showed a significant difference between SGA and AGA children. Overall, median
      IGF1 levels were approximately one SDS below zero SDS (p < 0.001), whereas IGFBP3
      levels were normal in both groups. Thus, the IGF1:IGFBP3 molar ratios were
      significantly lower from zero (p < 0.01) in SGA as well as in AGA children.
      However, IGF1- and IGFBP3-SDS levels related either to chronological or to bone
      age did not differ significantly between SGA and AGA children. CONCLUSIONS:
      Building matched pairs of short statured children born either SGA or AGA for sex,
      age and BMI we did not find any significant differences in spontaneous nocturnal
      GH secretion, IGF1, IGFBP3, and IGF1:IGFBP3 molar ratios.

PMID- 15519255
TI  - Lack of contribution of 11betaHSD1 and glucocorticoid action to reduced muscle
      mass associated with reduced growth hormone action.
AB  - 11Beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1) is expressed in several
      tissues and converts inactive glucocorticoids (GC) to active GC. 11betaHSD1
      activity, evaluated by urine cortisol metabolites, is increased in patients with
      hypopituitarism and decreased by GH replacement. Skeletal muscle wasting is one
      of the major characteristics of GH deficiency (GHD). We hypothesized that
      increased 11betaHSD1 activity and increased GC action in skeletal muscle may play
      a role in the development of muscle atrophy observed in GHD patients. Glutamine
      synthetase (GS) mRNA in muscle has been reported to be related to GC-induced
      muscle atrophy. In this study, we measured mRNA levels of 11betaHSD1 and GS in
      skeletal muscle of GH receptor gene disrupted (GHR-/-) mice and of their age
      matched wild-type mice controls to elucidate the physiological significance of
      11betaHSD1 and GC in the development of GHD-associated muscle atrophy in vivo. We
      also measured the expression of these genes in hypertrophied muscles of giant,
      bovine GH transgenic mice. In skeletal muscle, although IGF-I mRNA levels were
      decreased in GHR-/- mice, 11betaHSD1 mRNA levels were not significantly changed
      compared to wild-type mice. In addition, expression level of 11betaHSD1 in muscle
      was lower compared to that seen in liver. GS mRNA in skeletal muscle of GHR-/-
      mice was not significantly different from that of controls. In bGH mice,
      11betaHSD1 and GS mRNA levels were not altered compared to control mice. These
      data do not support a significant role of 11betaHSD1 and GC action in skeletal
      muscle in the development of muscle atrophy associated with GHD.

PMID- 15519256
TI  - Guidelines on management (diagnosis and treatment) of syncope--update 2004.

PMID- 15519257
TI  - Closed loop stimulation in prevention of vasovagal syncope. Inotropy Controlled
      Pacing in Vasovagal Syncope (INVASY): a multicentre randomized, single blind,
      controlled study.
AB  - OBJECTIVES: To determine whether dual-chamber rate-adaptive Closed Loop
      Stimulation (CLS) could prevent recurrence of Vasovagal Syncope (VVS).
      BACKGROUND: During VVS, an increase in myocardial contractility associated with a
      reduction of ventricular filling produces an increase in baroreceptor afferent
      flow and a consequent decrease in the heart rate. The CLS algorithm is a form of
      rate-adaptive pacing, which responds to myocardial contraction dynamics, by
      measuring variations in right ventricular intracardiac impedance: during an
      incipient VVS it could increase paced heart rate and avoid bradycardia, arterial
      hypotension and syncope. METHODS: Fifty patients (27 males, mean age 59+/-18
      year) with severe and recurrent vasovagal syncope and positive Head Up Tilt Test
      (HUTT) with cardioinhibition, received a CLS pacemaker (INOS2, Biotronik GmbH
      Co., Germany). The primary end point was recurrence of two VVSs during a minimum
      of 1 year of follow-up. Randomization between DDD-CLS and DDI mode (40 bpm)
      pacing was performed only during the first stage of the study (first year): 9/26
      randomized to DDI mode (control group) and 17/26 in DDD-CLS mode. All the 24
      patients recruited in the second stage of the study (second year) were programmed
      in DDD-CLS mode. RESULTS: Of the nine patients randomized to the DDI mode, seven
      had recurrences of syncope during the first year. At the end of the first year
      the nine patients were reprogrammed to the CLS mode and no syncope occurred after
      reprogramming. The 41 patients programmed to CLS had a mean follow-up of 19+/-4
      months: none reported VVS, only four (10%) reported occasional presyncope and
      their quality of life greatly improved. Positive HUTT at the end of the first
      year failed to predict the clinical response to CLS pacing. CONCLUSIONS: The
      study demonstrates the effectiveness of CLS pacing in preventing cardioinhibitory
      VVS. A possible placebo effect of pacemaker implantation occurred in 22% of
      patients.

PMID- 15519258
TI  - The head-up tilt test -- a cause of myocardial infarction.
AB  - INFARCTION: A 74-year-old man with no known ischaemic heart disease presented to
      the Cardiology Department with a history of multiple episodes of pre-syncope.
      During a head-up tilt test to investigate a neurocardiogenic cause, after
      glyceryl trinitrate provocation he became profoundly hypotensive and unwell.
      Subsequent ECGs and Troponin-T levels confirmed a Non ST-Elevation Myocardial
      Infarction. Angiography confirmed coronary artery disease. This case highlights a
      rare complication of tilt testing and emphasises that the test is not without
      risk.

PMID- 15519259
TI  - Understanding capture detection.
AB  - Automatic capture detection systems are currently available in several cardiac
      pacing devices. All current systems use low-polarization electrodes and no beat
      to beat detection system is available for all types of electrodes. In addition
      the success ratio for currently available systems is not always 100%. Failure to
      detect capture reliably is often related to the behaviour of the electrode-tissue
      interface under different circumstances. Pacemaker electrodes can be considered
      electrochemical cells with complicated characteristics depending on time,
      temperature and electrical charge. This electrochemical cell is disturbed when a
      charge is transferred across the electrode-tissue interface during pacing.
      Several measures can be taken in order to minimise this disturbance or pace
      polarization artefact (PPA) including the use of high active surface area
      electrodes and application of tri-phasic pacing pulses. Another factor
      influencing detection of evoked potentials is the input circuit of the pacemaker
      affecting the PPA and the evoked response. Positive PPAs can be falsely
      interpreted as evoked potentials due to the undershoot of the second order
      filters applied in modern cardiac pacemakers. This paper explains the behaviour
      of the interface between the electrode and the cardiac tissue in combination with
      the pacemaker output circuits and input amplifiers under different circumstances.

PMID- 15519260
TI  - Reduction of the pace polarization artefact for capture detection applications by
      a tri-phasic stimulation pulse.
AB  - This study investigated the ability to minimize pace polarization artefacts (PPA)
      by adjusting the post-stimulus pulse duration of a tri-phasic stimulation pulse.
      Adjustment of the stimulation pulse was enabled by downloading special study
      software into an already implanted pacemaker. Tests were performed in a total of
      296 atrial leads and 311 ventricular leads. Both chronic and acute leads were
      included in the study. Statistically significant differences were found in the
      initial PPA (without any adjustment of the stimulus pulse) between atrial and
      ventricular leads. In addition, significant differences were observed among
      various lead models with respect to changes over time in the initial ventricular
      PPA. Successful PPA reduction was defined as a reduction of the PPA below 0.5 mV
      for atrial leads and below 1 mV for ventricular leads. Results show a success
      rate for ventricular and atrial PPA reduction of 97.8% and 98.7%, respectively.
      Threshold tests showed that after reduction of the PPA loss of ventricular
      capture can be reliably detected. However, atrial threshold tests showed many
      false positive evoked response detections. In addition, unexpectedly high evoked
      response amplitudes were observed in the atrium after reduction of the PPA.
      Results from additional measurements suggest that these high atrial evoked
      response amplitudes come from the influence of the input filter of the pacemaker.

PMID- 15519261
TI  - Evaluation of pacemaker telemetry as a diagnostic feature for detecting atrial
      tachyarrhythmias in patients with sick sinus syndrome.
AB  - AIM: The aim of the present study was to validate pacemaker telemetry as a
      diagnostic feature for detecting atrial tachyarrhythmias (AT) during pacemaker
      treatment in patients with sick sinus syndrome (SSS). METHODS AND RESULTS:
      Patients with SSS and bradytachy syndrome (n = 28, 20 women), mean age 71 +/-
      10.3 years, were included. The patients were treated with AAIR (n = 14) or DDDR
      pacing. At a routine follow-up visit pacemaker telemetry was reset and the
      patients underwent Holter recording for at least 24 h. Episodes of atrial
      fibrillation (AF) during Holter recording were compared with episodes of AT
      detected by the pacemaker. Only episodes of AF lasting for at least 1 min during
      Holter recording were registered. AT detected by the pacemaker telemetry was
      defined as: an atrial high rate episode with a rate of > or = 220 bpm for > or =
      5 min, atrial sensing with a rate of > or = 170 bpm in > or = 5% of total counted
      beats, mode-switching in > or = 5% of total time recorded or a mode-switching
      episode of > or = 5 min. Twenty-eight Holter recordings (mean duration 31.5 h,
      range 20-72 h) were used for evaluation. Ten patients had one or more episodes of
      AF lasting at least 1 min on their Holter recordings. Nine of these patients had
      AT detected by their pacemaker telemetry according to our criteria. None of the
      patients had AT detected by the pacemaker telemetry and not by the Holter
      recording. The specificity and sensitivity for detection of AT recorded by the
      pacemaker telemetry in this study was 100% and 90%, respectively. The false
      positive rate was 0%. CONCLUSION: Pacemaker telemetry was found to be a reliable
      tool for detecting AT in patients with SSS.

PMID- 15519262
TI  - Reduction in hospitalization rates following cardiac resynchronisation therapy in
      cardiac failure: experience from a single centre.
AB  - AIMS: Frequent, lengthy hospital admissions for congestive cardiac failure (CCF)
      result in excessive health care costs. Cardiac resynchronisation therapy (CRT) is
      a novel treatment option for patients with CCF and associated cardiac conduction
      defects. We investigated whether CRT resulted in significant improvements in New
      York Heart Association (NYHA) symptom class, exercise tolerance, and
      hospitalization rates in such patients. METHODS: Twenty-seven patients who
      underwent CRT in a single centre were studied, with NYHA symptom class, exercise
      tolerance and hospitalization rates noted in the 12 months prior to and following
      CRT. RESULTS: Following 12 months of CRT, NYHA symptom class improved from 3.3 +/
      0.5 to 2.1 +/- 0.4 (P < 0.05). Exercise tolerance, assessed by 6 min hall walk
      test increased by 64% from 195 +/- 114 m to 320 +/- 85 m (P = 0.007). Days in
      hospital for stabilisation of cardiac failure decreased by 98% from 472 to 9 days
      (P < 0.001). Significant hospitalization cost savings of 201,684 euros were
      calculated, with an overall saving of 12,420 euros. CONCLUSIONS: These data
      demonstrate that CRT results in significant improvement in clinical parameters,
      and considerable reductions in hospital admissions, and costs in patients with
      CCF.

PMID- 15519263
TI  - A new treatment for atrial fibrillation based on spectral analysis to guide the
      catheter RF-ablation.
AB  - BACKGROUND: By studying the spectrum of atrial potentials by fast Fourier
      transform (FFT) we have found two types of atrial muscle: the compact (CM) and
      the fibrillar (FM) myocardium. The former presents normal in-phase conduction
      inferring a great number of cellular connections, long-lasting refractoriness and
      leftward FFT-shift. The latter shows anisotropic out-of-phase conduction, fewer
      cellular connections, short refractoriness and a segmented right-FFT-shift. The
      compact is the normal predominant muscle and the fibrillar is different and may
      be neural input, vein insertion, interatrial (1A) septum, left atrial (LA) roof,
      etc. or pathological tissue, being so by loss of cellular connections this is a
      possible mechanism for conversion of compact into fibrillar-like myocardium.
      During atrial fibrillation (AF), clusters of FM (AF nests) present higher
      frequencies than any surrounding tissue. PURPOSE: The purpose was to describe a
      new method for paroxysmal AF RF-ablation targeting AF nests. METHOD: Forty
      patients, six control and 34 having idiopathic drug-refractory paroxysmal or
      persistent AF were studied and treated. Two catheters were placed in the LA by
      transseptal approach. RF (30-40 J/60-70 degrees C) was applied to all sites
      outside the pulmonary veins (PV) presenting right-FFT-shift (AF nests). RESULTS:
      Numerous AF nests were found in 34/34 AF patients and only in 1/6 controls (only
      in this case it was possible to induce AF despite an absence of AF history). The
      main FM sites were: LA roof, LA septum, close to the insertion of the superior
      PV, near the insertion of the inferior PV, LA posterior wall, RA near the
      superior vena cava insertion, RA lateral and anterior wall and the right IA
      septum. Ablation of all AF nests near PV insertions resulted in 35 PV isolations.
      After 9.9 +/- 5 months only two AF patients presented relapse of a different AF
      form (coarse AF) which was very well controlled with medication previously
      ineffective. The AF was more frequent as the ratio FM/CM increased. CONCLUSIONS:
      The RF-ablation of AF nests decreasing the fibrillar/compact myocardium ratio
      eliminated 94% of the paroxysmal AF in patients in the FU of 9.9 +/- 5 months.
      The AF nests may be easily identified by spectral analysis and seem to be the
      real AF substrate. Paroxysmal AF may be cured or controlled by applying RF in
      several places outside the PV and, thereby, avoiding PV stenosis.

PMID- 15519264
TI  - Comparison of the effects of ipratropium bromide and salbutamol on autonomic
      heart rate control.
AB  - AIMS: B2-agonists and anticholinergic drugs may alter cardiac autonomic
      modulation. The aim of this study was to investigate the effects of inhaled
      salbutamol and ipratropium bromide on heart rate variability (HRV). METHODS AND
      RESULTS: A randomized, double-blind, crossover design study was conducted on 13
      healthy volunteers. Salbutamol, ipratropium or placebo was administered in three
      different testing sessions. Time domain parameters; mean R-R interval (mean-RR),
      the standard deviation of R-R interval (SDNN) and the root mean square of
      successive R-R interval differences (RMSSD) and power spectral analysis of HRV
      were assessed in the supine position and during handgrip exercise before and
      after taking each drug. In time domain analyses, ipratropium administration
      resulted in a reduced mean-RR, SDNN and RMSSD during handgrip exercise compared
      with baseline values (775 +/- 30 ms vs. 748 +/- 21 ms, P < 0.05; 57 +/- 5 ms vs.
      50 +/- 5 ms, P < 0.05; 30 +/- 2 ms vs. 26 +/- 2 ms, P < 0.01, respectively). This
      effect was not detected with salbutamol or placebo administration. In frequency
      domain analyses, salbutamol but not ipratropium and placebo inhalation increased
      high frequency power/total power during handgrip exercise compared with baseline
      (0.09 +/- 0.02 vs. 0.12 +/- 0.02, P < 0.05). CONCLUSION: Ipratropium inhalation
      may alter autonomic control of the heart rate in therapeutic doses during mild
      sympathetic stimulation in healthy subjects, while salbutamol does not show these
      effects.

PMID- 15519265
TI  - Electroanatomical mapping and radiofrequency ablation of an accessory pathway
      associated with a large aneurysm of the coronary sinus.
AB  - We report a case of a patient with a left posteroseptal accessory pathway
      associated with a coronary sinus (CS) aneurysm. The patient had undergone two
      previous failed ablation attempts at other institutions despite multiple
      radiofrequency applications delivered within and outside the CS aneurysm.
      Electroanatomical mapping was performed and allowed delineation of the three
      dimensional anatomy of the aneurysm, so as to identify the ventricular insertion
      site, and to permit successful ablation of the pathway without any complications.

PMID- 15519266
TI  - Spontaneous and induced pulmonary vein tachycardia after pulmonary vein
      isolation.
AB  - A case is reported of recurrence of paroxysmal atrial fibrillation after
      pulmonary vein ablation. A second procedure achieved isolation of three pulmonary
      veins and showed persistence of pulmonary vein tachycardia in one with
      implications concerning the electrophysiology of atrial fibrillation.

PMID- 15519267
TI  - Verification of implantable cardioverter defibrillator (ICD) interventions by
      nonlinear analysis of heart rate variability -- preliminary results.
AB  - AIMS: Conventional ICD algorithms yield approximately 10-30% of spurious
      interventions. Our aim was to check whether nonlinear dynamics methods might be
      useful in the verification of ICD interventions. METHODS AND RESULTS: We
      extracted 190 consecutive RR files (approximately 2000-9000 RR intervals long)
      from the ICDs of 70 patients (36 with coronary artery disease, 8 with
      hypertrophic cardiomyopathy, 19 with dilated cardiomyopathy and 7 with other
      diseases). The 3D phase space trajectories in delay coordinates, window pattern
      entropy, and algorithmic complexity of the RR intervals were examined within a 50
      beat sliding window. Data were not filtered for arrhythmia and artefacts. Of the
      83 recordings with appropriate interventions 79 were correctly recognised in a
      blind test. Two interventions were not identified in patients with fast atrial
      fibrillation and two in cases of complex and frequent forms of arrhythmia. There
      were nine spurious interventions. In all except one case (atrial fibrillation
      with a fast ventricular response) the analysis by nonlinear methods showed that
      the intervention was not necessary. All of the 98 control recordings were
      correctly identified in the blind test. CONCLUSIONS: The results show that
      nonlinear dynamics methods may be used to supplement the existing ICD detection
      algorithms to enhance the detection success rate.

PMID- 15519268
TI  - Transmission of hepatitis C virus quasispecies between human adults.
AB  - To elucidate how hepatitis C virus (HCV) with multiple variants (quasispecies) is
      transmitted and adapts to the host during infection, we compared nucleotide and
      deduced amino acid sequences from hypervariable region1 (HVR1) of the E2 gene of
      HCV between a donor and a recipient who developed hepatitis after a needlestick
      accident. Thirty clones from each subject were sequenced after PCR amplification,
      cloning, and purification of plasmid DNA from single colonies of transformed
      bacteria. Genetic analysis revealed that the recipient's viral sequences were
      much less diverse than the donor's. We found a single predominant HCV HVR1 clone
      of the recipient in 22/30 isolates with the same amino acid sequence, and mimic
      clones in 8/30 isolates with only one amino acid substitution. These were all
      absent in the donor, who had 21 highly diverse sequences. Phylogenetic analysis
      of virus E1/E2 gene sequences showed that the recipient's unique sequences were
      related to the population of variants from the donor, in whom one isolate had 96%
      similarity to the recipient's predominant amino acid sequence. These results
      suggest that a minor subset of the donor's HCV variants is selectively
      transmitted to the recipient, and that the selection determines the predominant
      variant in the new host.

PMID- 15519269
TI  - Prediction of treatment outcome with daily high-dose IFN alpha-2b plus ribavirin
      in patients with chronic hepatitis C with genotype 1b and high HCV RNA levels:
      relationship of baseline viral levels and viral dynamics during and after
      therapy.
AB  - Data on 334 patients with HCV genotype 1b and high viral levels were extracted
      from two multicenter double-blind studies conducted in Japan comparing IFN alpha
      2b plus ribavirin (n = 209) with IFN alpha-2b alone (n = 125) for 24 weeks. HCV
      RNA assay was conducted before and 4, 12, and 24 weeks after the start and 4, 12,
      and 24 weeks after the end of treatment. Both sustained viral response (SVR) rate
      and relapse rate after the end of treatment were analyzed in relation to baseline
      viral levels and the time of first disappearance of virus. In the combination
      treatment group, the percentage of patients who were HCV RNA-negative within 4
      weeks decreased with increase in baseline viral levels (i.e. 42%, 15%, and 11%
      were HCV RNA-negative in the groups exhibiting <500, 500 to <850, and
      >/=850kcopies/mL, respectively). In the IFN monotherapy group, the response rates
      were lower at 13%, 15%, and 1%, respectively. Disappearance of virus within 12
      weeks after the start of combination treatment was indicative of higher
      probability of SVR. The risk of relapse was more highly correlated with the
      timing of initial viral disappearance than with baseline HCV levels; it was 4.8
      and 10.3 times higher in patients who became HCV-negative at 4-12 and 13-24 weeks
      compared with in those who were HCV-negative within 4 weeks.

PMID- 15519270
TI  - Development of quantitative neuropsychological tests for diagnosis of subclinical
      hepatic encephalopathy in liver cirrhosis patients and establishment of
      diagnostic criteria-multicenter collaborative study in Japanese.
AB  - At present, there are no generally accepted diagnostic criteria or methods for
      subclinical hepatic encephalopathy (SHE) associated with liver cirrhosis. We
      therefore developed an easily conducted computer-aided quantitative
      neuropsychiatric function test system for use in routine medical practice. We
      established normal values in healthy Japanese subjects and determined differences
      between healthy persons and liver cirrhosis patients without clinical
      encephalopathy in a multi-center clinical trial. The test system consists of
      eight tests: number connection tests A and B, a figure position test, a digit
      symbol test, a block design test, and reaction time tests A, B and C. The test
      results were affected by age, but not by gender or facility. No learning effect
      was noted. The results were therefore reported by 5-year quartile ranges and
      differences were evaluated between 542 healthy subjects and 292 cirrhotic
      patients. When the cut-off value was set at the 10th/90th percentile of the
      results in healthy subjects, the results of each of the 8 tests were abnormal in
      about 25% of cirrhotic patients, and at least 1 of the 8 tests gave values
      greater than the 10th/90th percentile cut-off value in 58.2% of the 292 liver
      cirrhosis patients. SHE patients were thought to be included in these 58.2% of
      patients. The developed test makes it possible to quantitatively assess
      neuropsychiatric function, and the results obtained can be used as a basis for
      the diagnosis of SHE.

PMID- 15519271
TI  - The effect of octreotide on fasting and postprandial splanchnic hemodynamics in
      cirrhosis.
AB  - The effect of octreotide on splanchnic hemodynamics was examined in cirrhotic
      patients both in the fasting and postprandial states using echo-Doppler
      flowmetry. The splanchnic parameters examined were portal venous blood flow
      (PVBF), superior mesenteric venous blood flow (SMVBF), and splenic venous blood
      flow (SPBF). In the fasting state, nine cirrhotic patients were examined at
      baseline and at 30 and 60min after octreotide administration. In the postprandial
      state, 16 cirrhotic patients were investigated in a prospective, placebo
      controlled, crossover study. Data were collected at baseline, 30min after a
      standard liquid meal and at 30 and 60min after octreotide or placebo
      administration. In the fasting state, octreotide induced a mild reduction both in
      PVBF (-16%) and SMVBF (-12%). In contrast, in the postprandial state, octreotide
      induced a significantly larger decrease in PVBF (-32%) and SMVBF (-32%). SPBF
      showed no significant changes in either the fasting or postprandial state.
      Octreotide suppressed the release of glucagon, and in the postprandial state,
      changes in SMVBF significantly correlated with changes in glucagon after
      octreotide administration. We conclude that octreotide significantly reduces PVBF
      and SMVBF in the postprandial state, but has comparatively little effect in the
      fasting state, and may act via suppression of glucagon.

PMID- 15519272
TI  - Mutation analysis of the multidrug resistance protein 2 (MRP2) gene in a Japanese
      patient with Dubin-Johnson syndrome.
AB  - Dubin-Johnson syndrome (DJS) is a recessive inherited disorder with conjugated
      hyperbilirubinemia caused by a dysfunction of multidrug resistance protein 2
      (MRP2) on the canalicular membrane of hepatocytes. A mutational analysis of the
      MRP2 gene was carried out in a Japanese female with DJS. In this patient, we
      found a homozygous 2125T > C mutation in exon 17. This mutation affects the
      conversion of tryptophan(709) to arginine(709) (W709R) in the first ATP-binding
      cassette in the MRP2 protein. It was concluded that this homozygous mutation of
      the MRP2 gene contributed to the induction of hyperbilirubinemia in this case.

PMID- 15519273
TI  - Influence of common variants in the pharmacokinetic genes (OATP-C, UGT1A1, and
      MRP2) on serum bilirubin levels in healthy subjects.
AB  - To assess the contribution of OATP-C to the hepatobiliary transport of bilirubin,
      a pharmacogenomic evaluation with regard to polymorphisms of three candidate
      genes, OATP-C, MRP2, and UGT1A1, was performed. Serum total and direct
      (conjugated) bilirubin levels were used as phenotypic indexes. Pharmacokinetic
      variables of pravastatin, a typical substrate for OATP-C, were obtained from our
      previous study. Among 23 volunteers, two variants (Val417Ile and Ser789Phe) were
      observed in the MRP2 gene. While there was no apparent effect of these two
      variants and the UGT1A1*28 on direct bilirubin levels, the OATP-C variants were
      associated with differences in unconjugated bilirubin levels. Subjects with the
      OATP-C*15 allele had higher bilirubin levels; unconjugated bilirubin levels in
      *1b/*1b (n = 3), *1b/*15 (n= 7), and *15/*15 (n = 1) subjects were 0.40 +/- 0.10,
      0.77 +/- 0.35, and 0.70 (mg/dL), respectively. In addition, the correlation
      between unconjugated bilirubin levels and pharmacokinetic parameters of
      pravastatin revealed that the subjects with higher bilirubin levels had lower non
      renal clearance values, and then higher serum concentrations of pravastatin.
      Large clinical studies are needed to confirm a role of OATP-C in the carrier
      mediated uptake of bilirubin in the human liver.

PMID- 15519274
TI  - Hepatic resection leads to predominance of the T helper-2 lymphocyte phenotype.
AB  - Recent studies have shown that the type 1/2 T helper (Th1/2) cell balance is
      shifted toward a Th2-type immune response not only by malignancy but also by
      surgical stress. This study evaluates in immune responses to surgical stress from
      liver surgery in comparison with other major abdominal surgeries. PATIENTS AND
      METHODS:: Eighty-five patients who underwent abdominal surgeries were divided
      into three groups: hepatic resection (n = 17), gastric resection (n = 38), and
      colorectal resection (n = 30). Blood sampling was performed before surgery, and
      on postoperative days (POD) 2 and 14. Cell surface markers were used to
      characterize Th1/2 balance by flow cytometry and a ratio of the percent IFN-gamma
      producing (Th1) cells to IL-4-producing (Th2) cells were expressed as the Th1/2
      balance. RESULTS:: The postoperative ratio of Th1 to Th2 was decreased
      significantly in all subjects to 4.5 +/- 3.0 on POD 2 from 6.7 +/- 4.2. The ratio
      of Th1 to Th2 in patients who underwent hepatic resection markedly decreased to
      2.8 +/- 1.6 on POD 2, significantly different from those in patients undergoing
      gastric resection or colorectal resection. However, on POD 14 there were no
      longer any significant differences among the three surgical groups. CONCLUSIONS::
      This study shows that hepatic resection induces a more marked shift of the Th1/2
      balance toward Th2 than other major abdominal surgeries.

PMID- 15519275
TI  - Lack of peroxisome proliferator-activated receptor alpha in mice enhances
      methionine and choline deficient diet-induced steatohepatitis.
AB  - Pathogenesis of steatohepatitis, a common liver disease, remains controversial.
      It is proposed that fatty liver with a second hit capable of inducing
      necroinflammation results in nonalcoholic steatohepatitis. Long chain and very
      long chain fatty acids are considered important in induction of steatohepatitis.
      Peroxisome proliferator-activated receptor alpha (PPARalpha) plays an important
      role in beta-oxidation of long chain and very long chain fatty acids and
      mitogenic effect caused by peroxisome proliferators in the liver. To determine
      the role of PPARalpha in the pathogenesis of steatohepatitis and compensatory
      liver cell hyperplasia, we have used PPARalpha null mice and methionine and
      choline deficient nutritional model. Male and female PPARalpha null mice and wild
      type mice were fed methionine and choline deficient diet (MCDD) or normal chow
      for 4 weeks. Livers were analyzed morphologically for steatosis, steatohepatitis
      and hepatocyte proliferation (PCNA labeling) and biochemically for triglyceride
      levels. In addition, serum alanine transaminase, aspartate transaminase and
      triglyceride levels were measured. In MCDD fed PPARalpha null mice there was
      severe steatohepatitis and very high liver triglyceride levels compared to wild
      type mice. Serum aspartate transaminase levels were also significantly higher in
      MCDD fed PPARalpha null mice compared to wild type mice. The severity of
      steatohepatitis in MCDD fed male and female PPARalpha null mice was greater
      compared to wild type mice fed the same diet. The PCNA labeling index was similar
      in PPARalpha null mice and wild type mice fed MCDD, and significantly higher in
      both the groups compared to the mice fed control diet. These findings indicate
      that defective fatty acid oxidation aggravates steatohepatitis caused by
      methionine and choline deficiency and further establishes the role of long chain
      and very long chain fatty acids in the pathogenesis of steatohepatitis. In
      addition, the results of this study also indicate that there is no difference
      between males and females in the severity of steatohepatitis induced by MCDD and
      lack of PPARalpha does not affect compensatory hyperplasia in the liver.

PMID- 15519276
TI  - Six cases of primary biliary cirrhosis complicated by psoriasis.
AB  - Six cases of primary biliary cirrhosis (PBC) complicated by psoriasis are
      presented. Three of six patients had psoriasis vulgaris and three had
      palmoplantar pustulosis. PBC was diagnosed before the onset of psoriasis in three
      patients and after the onset of psoriasis in the other three patients.
      Interestingly, all three cases of psoriasis vulgaris were diagnosed after the
      onset of PBC. We recognized no obvious characteristics specific to PBC
      complicated by psoriasis except that all cases were in an early stage of PBC.
      Although the etiologies of psoriasis and PBC remain unknown, the two diseases
      have many common features as to pathogenesis. We believe that case of PBC
      psoriasis overlap hold the key to clarifying the nature of these diseases.

PMID- 15519277
TI  - HNF-4alpha: from MODY to late-onset type 2 diabetes.
AB  - Maturity-onset diabetes of the young (MODY) is a rare subtype of type 2 diabetes
      that is characterized by autosomal-dominant inheritance and can be caused by
      mutations in hepatocyte nuclear factor 4alpha (HNF-4alpha). Odom and colleagues
      have combined chromatin immunoprecipitation with promoter microarrays to identify
      numerous promoters occupied by HNF-4alpha in the human liver and islet,
      suggesting a very broad role for HNF-4alpha in glucose homeostasis. This notion
      is supported by recent genetic studies linking HNF-4alpha to the much more common
      late-onset type 2 diabetes.

PMID- 15519279
TI  - JAK3 inhibition, a viable new modality of immunosuppression for solid organ
      transplants.
AB  - The field of organ transplantation has had tremendous success because of the
      availability of immunosuppressive drugs that efficiently prevent acute organ
      rejection. Numerous and severe side effects are, however, associated with all
      current immunosuppressive therapies and justify a search for drugs with better
      efficacy and safety profiles. Janus kinase (JAK) 3, a tyrosine kinase that is
      crucial for mediating signals from the common gamma-chain of cytokine receptors,
      is peculiar in that its expression, contrarily to the targets of most current
      immunosuppressive drugs, is limited to cells that actively participate to the
      immune response to allografts. The recent demonstration in stringent preclinical
      models that JAK3 inhibition results in efficacy for the prevention of allograft
      rejection with a narrow side-effect profile might lead to a new era in the field
      of immunosuppression.

PMID- 15519278
TI  - The multifactorial nature of HIV-1 latency.
AB  - HIV-1 can avoid host immune responses and antiretroviral drugs through the latent
      infection of resting memory CD4(+) T cells. Recently, latent viral genomes have
      been shown to reside within the introns of active host genes. Therefore, latency
      is not simply due to an inaccessibility of the integrated proviruses to the
      transcriptional machinery. Rather, latency might result from insufficient nuclear
      levels of the crucial activation-dependent host transcription factors required to
      overcome the transcriptional interference that is an automatic consequence of the
      nature of HIV-1 integration sites. In addition, resting cells lack sufficient
      levels of HIV-1 Tat and Tat-associated activation-dependent host factors that are
      necessary for processive transcription. Defects at consecutive steps of
      transcriptional initiation and elongation enable HIV-1 to remain hidden within
      resting CD4(+) T cells.

PMID- 15519280
TI  - Oncogenic transformation of human cells: shortcomings of rodent model systems.
AB  - Long-standing difficulties in the in vitro transformation of human cells have
      been overcome. Using telomerase, several successful oncogene-mediated
      transformations of human cells have been reported and the following cellular
      requirements for human cell transformation have been proposed: the maintenance of
      telomere sequences, the inactivation of Rb and p53 pathways, the perturbation of
      protein phosphatase 2A (PP2A) and the expression of activated Ras. Even when all
      of these requirements are fulfilled, however, the transformed phenotypes of human
      cells seem to be much less malignant than those of rodent cells meeting the same
      requirements. This suggests the existence of undefined cell-autonomous mechanisms
      that render human cells resistant to malignant transformation.

PMID- 15519281
TI  - Nrf2-Keap1 defines a physiologically important stress response mechanism.
AB  - The transcription factor Nrf2 regulates the basal and inducible expression of
      numerous detoxifying and antioxidant genes. The cytoplasmic protein Keap1
      interacts with Nrf2 and represses its function. Analysis of keap1-knockout mice
      provides solid evidence that Keap1 acts as a negative regulator of Nrf2 and as a
      sensor of xenobiotic and oxidative stresses. The simultaneous ablation of the
      keap1 and nrf2 genes reversed all apparent phenotypes of the Keap1-deficient
      mice, suggesting that Nrf2 is a primary target of Keap1. The Nrf2-Keap1 system is
      now recognized as one of the major cellular defence mechanisms against oxidative
      and xenobiotic stresses. Furthermore, extensive studies have suggested that the
      Nrf2-Keap1 system contributes to protection against various pathologies,
      including carcinogenesis, liver toxicity, respiratory distress and inflammation.

PMID- 15519282
TI  - Roles for bone-marrow-derived cells in beta-cell maintenance.
AB  - With more than 177 million people suffering from diabetes worldwide, and the
      number expected to double by 2030, finding new ways to treat this disease is a
      high priority. Intensive effort is being directed towards developing mechanisms
      for increasing beta-cell expansion as a diabetic therapeutic. Recent studies, in
      which adult bone marrow has been used to induce beta-cell expansion in mice, have
      shown both exciting and controversial results. In these reports, marrow-derived
      cells can contribute towards beta-cell maintenance both by promoting endogenous
      beta-cell expansion and possibly by transdifferentiation into beta-cells. These
      studies reveal mechanisms for potential therapeutic intervention.

PMID- 15519283
TI  - Alzheimer's disease meets the ubiquitin-proteasome system.
AB  - Ubiquitin-positive deposits are histopathologically found in patients with
      Alzheimer's disease (AD). It is not understood why ubiquitin is accumulated in
      intra- and extra-cellular deposits or how it is involved in AD pathogenesis.
      Interestingly, recent evidence, including studies of E2-25K/Hip-2, has elucidated
      the molecular mechanism of the ubiquitin-proteasome system (UPS) malfunction in
      AD. The neurotoxicity and proteasome inhibition by Abeta, a main cause of AD
      pathogenesis, are mediated by increased E2-25K/Hip-2 in the brains of patients
      with AD. Furthermore, E2-25K/Hip-2 is required for the neurotoxicity that is
      mediated by a ubiquitin B mutant (UBB+1), which is a potent inhibitor of
      proteasomes that is found in patients with AD. Intensive research is required to
      identify the components of the UPS that are involved in AD pathogenesis.

PMID- 15519285
TI  - The epidemiologic basis for population-wide cholesterol reduction in the primary
      prevention of coronary artery disease.
AB  - A number of recent epidemiologic observations support the need for new and
      broader strategies to reduce serum cholesterol levels on a population-wide basis.
      First, the limited data available suggest a halt in the declining incidence of
      coronary artery disease (CAD) in the United States since 1990, raising concerns
      about our current strategies to promote primary prevention of CAD. Data from the
      1970s and 1980s support a key role for population-wide cholesterol lowering as a
      strategy to reduce CAD. Second, large and carefully performed surveys support no
      further reductions in serum cholesterol levels in the US population since 1990.
      Is this observation and that of stagnating declines of CAD incidence a
      coincidence? Interestingly, the lack of cholesterol level reduction occurred in
      the setting of increased use of prescription cholesterol-lowering drugs,
      suggesting that drug treatment of the highest-risk persons alone will not shift
      the population curve. Third, the treatment gap persists, with recent population
      wide data suggesting that half of all people with hypercholesterolemia (>/=200
      mg/dL) are unaware of their condition, only half of those persons aware are
      treated, and only half of those treated are controlled. Finally, the moderate
      risk population (10% to 20% risk of CAD over 10 years) is sizable in the ages
      recommended for over-the-counter statin use (>/=45 years in men, >/=55 years in
      women). Risk reduction in this group, which contributes a significant portion of
      CAD cases, should be part of any program to reduce the population burden of CAD.

PMID- 15519286
TI  - Understanding physician and consumer attitudes concerning cholesterol management:
      results from the National Lipid Association surveys.
AB  - Two online surveys commissioned by the National Lipid Association (NLA) were
      conducted to determine the current attitudes of physicians and consumers
      regarding cholesterol and heart disease. Physicians and consumers from
      preexisting independent panels were randomly invited to participate in the online
      surveys that were open from January 26 to 30, 2004. Both physicians (n = 200) and
      consumers (n = 600) agreed that high cholesterol and coronary artery disease
      (CAD) are significant health risks. Physicians reported the primary barriers for
      patients being prescribed cholesterol-lowering medication as patient fear of side
      effects (61%) and reluctance to take prescription medications (52%). While most
      physicians were aware of and felt they adhered to the National Cholesterol
      Education Program Adult Treatment Panel III (NCEP ATP III) guidelines,
      considerably fewer thought the same of other physicians. The consumer survey
      focused on untreated moderate-risk patients (an approximate 10% to 20% 10-year
      risk of myocardial infarction and cardiac death) because this group is often
      undertreated. Untreated moderate-risk patients reported that their physicians did
      not advise them to take prescription cholesterol-lowering drugs (51%) and that
      they were trying to control their cholesterol with diet and exercise (58%).
      Consumers believe they are taking an increased role in their own health
      management and decision making. Current attitudes of physicians and consumers are
      similar with regard to their recognition of the significance of cholesterol and
      CAD for health, but differ with regard to why patients do not take prescription
      medications.

PMID- 15519287
TI  - The National Lipid Association surveys of consumers, physicians, and pharmacists
      regarding an over-the-counter statin in the United States: is this a good idea?
AB  - Surveys commissioned by the National Lipid Association (NLA) were conducted to
      determine the current attitudes and perceptions of physicians, consumers, and
      pharmacists regarding the impact of an over-the-counter (OTC) statin. Individuals
      from preexisting independent databases were randomly invited to participate in
      the online surveys that were open from January 26 to 30, 2004 for physicians and
      consumers and from March 1 to 12, 2004 for pharmacists. The results of these
      surveys indicate that consumers and pharmacists are more positive regarding the
      idea of an OTC statin, whereas physicians are more guarded. Concerns of both
      physicians and pharmacists included the discontinuation by patients of their
      prescription cholesterol-lowering therapy without consulting their physician,
      safety issues such as potential drug interactions and side effects, and patient
      ability to self-manage OTC statins. Consumers interested in purchasing an OTC
      statin reported that they would consult their physician before doing so, and
      pharmacists were interested in supporting consumers who use OTC statins. Although
      such support would require further training and time, pharmacists believed that
      they could facilitate consumer self-care programs and follow-up with physicians.

PMID- 15519288
TI  - Consumer behavior in the setting of over-the-counter statin availability: lessons
      from the consumer use study of OTC Mevacor.
AB  - Despite the proven benefits of statins, large numbers of patients meeting
      guideline criteria for therapy are not receiving these drugs. It has been
      suggested that over-the-counter (OTC) availability of statins would allow more
      consumers to use statins and achieve cardiovascular risk reduction. However,
      concerns have been raised as to the consumers' ability to self-manage
      hyperlipidemia and use statins safely. The Consumer Use Study of OTC Mevacor
      (CUSTOM) was designed to define consumer behaviors in the setting of OTC statin
      availability. The study was conducted in a simulated OTC setting and allowed
      consumers to purchase once-daily lovastatin 20 mg. The CUSTOM dataset includes
      >3,300 consumers who evaluated OTC lovastatin for potential purchase at study
      sites and follow-up information on purchasers for up to 6 months of self-managed
      therapy. These data have been analyzed to address consumers' knowledge of their
      cholesterol concentrations as well as their ability to make OTC use decisions
      based on their cardiovascular risk, avoid drug-drug interactions, self-manage
      their cholesterol treatment after deciding to use the OTC product, and maintain
      interactions with physicians while using lovastatin OTC. The results showed that
      most study participants appropriately self-selected OTC statin therapy and
      managed their treatment. Use of OTC statins by consumers needing more intensive
      statin therapy or facing the risk of potential drug-drug interactions remains an
      area of concern but occurred infrequently in CUSTOM. These data are important for
      making an informed risk-benefit decision concerning OTC statin availability.

PMID- 15519289
TI  - Is there value in liver function test and creatine phosphokinase monitoring with
      statin use?
AB  - Statins have transformed the care of patients with vascular disease. Patients in
      almost every category that has been studied have benefited substantially. On the
      other hand, although the incidence of side effects is remarkably low, statins,
      like any other therapy, are not entirely free of serious risks. From the outset,
      based on the mechanism of action of statins, hepatotoxicity has been a concern.
      Moreover, although the mechanisms remain obscure, significant skeletal muscle
      injury, which can lead to renal failure and death, unquestionably does occur. To
      mitigate these risks, screening and monitoring programs for hepatic and skeletal
      muscle injury were put in place when statins were introduced into clinical
      practice. This article reviews the benefits and the costs of these efforts.
      Although the benefits have not been shown, the costs are real and substantial.
      These include the harm caused by inappropriate withdrawal of therapy, which has
      been shown to be life-saving, as well as the considerable financial expenditure.
      The conclusion that follows, based on the evidence in hand, is that although
      these programs were appropriate at the time statins were introduced, they are not
      appropriate now.

PMID- 15519290
TI  - Reclassification of simvastatin to over-the-counter status in the United Kingdom:
      a primary prevention strategy.
AB  - Simvastatin (10-mg tablet) has been reclassified for sale as a pharmacy-only over
      the-counter medicine in the United Kingdom. It is designed to be a primary
      prevention agent targeting that segment of the population having a moderate risk
      of coronary artery disease (CAD). The anticipated effect is a reduction of risk
      of a first major coronary event (nonfatal myocardial infarction or CAD death).
      Simvastatin is a component of the Heart Health Programme, which also addresses
      other modifiable risk factors such as diet, exercise, and smoking. Men >/=55
      years of age, men aged 45 to 54 years with >/=1 risk factor, and women aged >/=55
      years with >/=1 risk factor have a moderate (10% to 15%) 10-year risk of
      developing CAD. Risk factors include having a first-degree relative with a
      history of early family CAD, smoking, being overweight, and South Asian
      ethnicity. Simvastatin 10 mg lowers low-density lipoprotein cholesterol levels by
      approximately 30%, with a resultant 33% reduction in risk of a major CAD event
      after 3 years. After the patient completes a check-box questionnaire regarding
      his or her medical history and other specific risk factors, the pharmacist
      performs a few simple physical measurements and makes a decision as to CAD risk
      and simvastatin eligibility. After 1 month of simvastatin therapy, cholesterol
      testing is highly recommended to patients, and a kit is made available that
      permits home blood collection and analysis at a central laboratory.

PMID- 15519291
TI  - Cloning, characterization, and structural analysis of a C-type lectin from
      Bothrops insularis (BiL) venom.
AB  - Lectins are carbohydrate-binding molecules that mediate a variety of biological
      processes. In this work, we identify and characterize a lectin from Bothrops
      insularis venom, with respect to its biochemical properties and theoretical
      structure. Initially, from a venom gland cDNA library, we cloned and sequenced a
      cDNA encoding a protein with high identity to snake venom lectins. A lectin
      molecule was purified to homogeneity from the venom by affinity column and gel
      filtration. This protein named BiL displayed hemagglutinating activity that was
      inhibited by galactose, lactose, and EDTA. Mass spectrometry analysis and sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis showed that BiL is a disulfide
      linked dimeric protein consisting of monomers with 16,206 m/z. The amino acid
      sequence, deduced from its cDNA sequence, was confirmed by Edman sequencing and
      by peptide mass fingerprint analysis. BiL shows similarity to other C-type lectin
      family members. Modeling studies provide insights into BiL dimeric structure and
      its structural determinants for carbohydrate and calcium binding.

PMID- 15519292
TI  - Cys-His proteases are among the wired proteins of the cell.
AB  - Integrated cell protein degradation can be paced by the transfer of reductive
      energy, as revealed by experimental agents of informative actions. The
      peptidolytic pair of Cys-His proteases can undergo oxidative reactions to
      inactive derivatives and inhibitory metal binding. Proton-dependent ionizations
      can modify ongoing activity. If the reaction rate of a Cys-His protease were
      found responsive to the ranges of metal/redox/proton factors regulated within the
      cell, then these factors might serve to link the peptidolytic reaction rate to
      cell controls. Here, cathepsin B (cat B) was found to be inhibited by Zn2+, Fe3+,
      and Cu2+ (1-50 microM) under excess GSH or DTT protease activators (6 mM). Under
      DTT or GSH (6 mM) the initial inhibitory action of Zn2+ is stable indefinitely;
      however, the inhibitory actions of Fe3+ and Cu2+ are reversed over approximately
      1h. The 12-14 min half time of reversal of initial protease inhibition is
      correlated with the measured reduction of Fe3+ to Fe2+ by DTT or GSH (pH 5.5 or
      6.5). Endogenous Fe2+ concentrations (100 microM) inhibit cat B only marginally.
      However, the inhibitory threshold of several microM Fe3+ is only a few percent
      oxidation of the endogenous pool. Without metals cat B reaction is reportedly
      proportional to GSH concentration, and is inhibited by increasing GSSG/GSH redox
      ratio. Following activation with GSH, cat B can be influenced by Fe3+/Fe2+,
      Cu2+/Cu+, and GSSG/GSH ratios and concentrations. Results are interpreted in
      relation to properties of the thiolate-imidazolium pair as illustrated by Dock
      modeling of their shared Fe3+ binding. It is proposed that the interaction of Cys
      His with 1 electron transition between Fe2+ and Fe3+ serves as a sensor, signal
      integrator and switch wiring cat B reaction rate to the transfer of reductive
      energy in the presence of excess GSH. Speciated metals might also serve among
      electron acceptors transferring from reduced protease to oxygen. Results provide
      a model for pharmacologic redox switching of protease functions with metal
      interactive drugs, and other nano-technology engineering.

PMID- 15519293
TI  - Porcine purple acid phosphatase: heterologous expression, characterization, and
      proteolytic analysis.
AB  - Uteroferrin is an iron-binding glycoprotein, which is abundantly synthesized in
      porcine uterine glandular endometrium and believed to be involved in
      maternal/fetal iron transport. In the present study, uteroferrin has been cloned
      and functionally expressed using baculovirus-infected insect host cells
      Spodoptera frugiperda. The work also addresses the possible role of proteolytic
      cleavage to facilitate the release of uteroferrin-bound iron. The enzyme secreted
      in culture medium exhibits a molecular mass and catalytic properties similar to
      native porcine uteroferrin. The specific activity was estimated at 233 U/mg using
      p-nitrophenyl phosphate as substrate. Partial cleavage of the enzyme with trypsin
      resulted in a 1.7-fold enhancement in specific activity and a two-subunit
      polypeptide as observed in preparations of most mammalian purple acid
      phosphatases. Digestion with the aspartic protease pepsin resulted in a 2.5-fold
      enzyme inactivation correlated with the appearance of low molecular weight
      polypeptide fragments and the release of enzyme-bound iron.

PMID- 15519294
TI  - Selective liberation of NO from S-nitrosocysteine with potassium thiocyanate, as
      monitored by an amperometric sensor.
AB  - S-Nitrosocysteine (CysNO) releases either NO (in the presence of divalent
      cations) or NO+ (in the presence of chelating agents). NO+ is then transferred to
      peptides or protein SH groups to form high-mass nitrosothiols. The aim of this
      work was the development of a specific reaction between thiocyanate (SCN-) and
      CysNO. This reaction selectively liberates NO from CysNO in the presence of high
      mass nitrosothiols. Free NO is measured with an amperometric sensor. We examine
      with this system the transnitrosylation reaction between CysNO and BSA at low
      molecular ratios and could assay nitrites, SNO-BSA, and CysNO in the incubation
      mixture without any preliminary purification steps.

PMID- 15519295
TI  - Molecular cloning of Mucor hiemalis endo-beta-N-acetylglucosaminidase and some
      properties of the recombinant enzyme.
AB  - Endo-M, endo-beta-N-acetylglucosaminidase from Mucor hiemalis, is known as a
      useful enzyme for the synthesis of neoglycopeptides due to its transglycosylation
      activity. We cloned the Endo-M gene encoding a putative 744 amino acids, which
      shows high identity to glycoside hydrolase family 85 endo-beta-N
      acetylglucosaminidases. The gene encoding Endo-M was expressed in protease
      deficient Candida boidinii with a molecular mass of 85 kDa as a monomeric form.
      Recombinant Endo-M could liberate both high-mannose type and biantennary complex
      type oligosaccharides from glycopeptides, which was same as the native enzyme.
      The Km and Kcat values for DNS-Man6GlcNAc2Asn were 0.51 mM and 8.25 s(-1),
      respectively. Recombinant Endo-M also exhibited transglycosylation activity
      toward high-mannose type and biantennary complex type oligosaccharides, which
      were transferred to alcohols, monosaccharides, oligosaccharides, and glycosides.
      To investigate about the catalytically essential amino acids of Endo-M, site
      directed mutagenesis was performed, and it was found that mutants E177G and E177Q
      completely abolished the hydrolytic activity and W228R partially abolished the
      transglycosylation activity.

PMID- 15519296
TI  - Initiation of mitochondrial-mediated apoptosis during cardiac reperfusion.
AB  - Reperfusion of myocardial tissue can result in programmed cell death.
      Nevertheless, relatively little information exists concerning pathways initiated
      in vivo that ultimately commit cardiac cells to apoptosis during
      ischemia/reperfusion. The goal of the present study was to determine whether
      mitochondrial-mediated mechanisms of apoptosis are initiated during in vivo
      cardiac ischemia/reperfusion. We provide evidence that the content of cytochrome
      c in the cytosol increases exclusively during reperfusion. Over the same time
      interval Bax, a pro-apoptotic protein implicated in release of cytochrome c from
      mitochondria, was found to disappear from cytosolic extracts. This was associated
      with the appearance of tightly associated Bax in the mitochondrial fraction.
      Cytochrome c from reperfused cytosolic extracts is present as a high molecular
      weight oligomer consistent with formation of the apoptosome. In addition, pro
      caspase-9 was found to disappear exclusively during reperfusion. Therefore, the
      results of the current study indicate that the mitochondrial-mediated pathway of
      apoptosis is initiated as a result of in vivo cardiac ischemia/reperfusion.

PMID- 15519297
TI  - Mapping tissue-specific genes correlated with age-dependent changes in protein
      stability and function.
AB  - Biophysical measurements indicative of protein stability and function were
      performed on crude extracts from liver, muscle, and lens of a genetically
      heterogeneous mouse population. Genetic information was used to search for
      quantitative trait loci (QTL) that influenced the biophysical traits, with
      emphasis on phenotypes that previously have been shown to be altered in aged
      animals. Spectroscopic and enzymatic assays of crude liver and muscle tissue
      extracts from approximately 600 18-month-old mice, the progeny of
      (BALB/cJxC57BL/6J)F1 females and (C3H/HeJxDBA/2J)F1 males, were used to measure
      the susceptibility of a ubiquitous glycolytic enzyme, glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH), to thermal denaturation. The rate constant for thermal
      inactivation of GAPDH correlated with markers on chromosome 5 (D5Mit79 and
      D5Mit251) for muscle lysates and chromosome 15 (D15Mit63 and D15Mit100) for liver
      tissue. The degree of variability of inactivation rate constants, a measure of
      the heterogeneity of muscle GAPDH in tissue extracts, was also associated with
      markers on chromosome 5 (D5Mit79 and D5Mit205). In addition, spectroscopic
      characteristics of extracted eye lens proteins were evaluated for their
      susceptibility to photooxidative stress. Absorbance and fluorescence emission
      characteristics of the lens proteins were mapped to QTL on chromosomes 5 and 15
      (D5Mit25 and D15Mit171) while the degree of heterogeneity in photochemical
      oxidation kinetics was associated with a marker on the chromosome 8 (D8Mit42).
      Recent work has shown that GAPDH possesses a number of non-glycolytic functions
      including DNA/RNA binding and regulation of protein expression. Tissue specific
      differences in GAPDH stability may have significant consequences to these
      alternate functions during aging.

PMID- 15519298
TI  - Isoforms of cAMP-dependent protein kinase in the bivalve mollusk Mytilus
      galloprovincialis: activation by cyclic nucleotides and effect of temperature.
AB  - Two different isoforms of cAMP-dependent protein kinase (PKA) have been partially
      purified from the posterior adductor muscle and the mantle tissue of the sea
      mussel Mytilus galloprovincialis. The holoenzymes contain as regulatory subunit
      (R) the previously identified isoforms Rmyt1 and Rmyt2, and were named PKAmyt1
      and PKAmyt2, respectively. Both cAMP and cGMP can activate these PKA isoforms
      completely, although they exhibit a sensitivity approximately 100-fold higher for
      cAMP than for cGMP. When compared to PKAmyt2, the affinity of PKAmyt1 for cAMP
      and cGMP is 2- and 3.5-fold higher, respectively. The effect of temperature on
      the protein kinase activity of both PKA isoforms was examined. Temperature
      changes did not affect significantly the apparent activation constants (Ka) for
      cAMP. However, the protein kinase activity was clearly modified and a remarkable
      difference was observed between both PKA isoforms. PKAmyt1 showed a linear
      Arrhenius plot over the full range of temperature tested, with an activation
      energy of 15.3+/-1.5 kJ/mol. By contrast, PKAmyt2 showed a distinct break in the
      Arrhenius plot at 15 degrees C; the activation energy when temperature was above
      15 degrees C was 7-fold higher than that of lower temperatures (70.9+/-8.1 kJ/mol
      vs 10.6+/-6.5 kJ/mol). These data indicate that, above 15 degrees C, PKAmyt2
      activity is much more temperature-dependent than that of PKAmyt1. This different
      behavior would be related to the different role that these isoforms may play in
      the tissues where they are located.

PMID- 15519299
TI  - Characterization of a partially folded intermediate of papain induced by
      fluorinated alcohols at low pH.
AB  - A systematic investigation of the effects of aqueous 1,1,1,3,3,3
      hexafluoroisopropanol (HFIP) and 2,2,2-trifluoroethanol (TFE) on the structure of
      acid-unfolded papain (EC. 3.4.22.2) was made using circular dichroism (CD),
      intrinsic tryptophan fluorescence, and 1-anilino 8-sulfonic acid (ANS) binding.
      At pH 2, papain exhibits substantial secondary structure as beta-sheet and is
      relatively less denatured as compared to 6 M guanidine hydrochloride (GdnHCl) but
      loses the persistent tertiary structure of the native state. Addition of HFIP and
      TFE caused an induction of alpha-helical structure as evident from the increase
      in the mean residue ellipticity value at 208 and 222 nm. Induction was 20% more
      in HFIP than TFE. Interestingly, at 13% (v/v) HFIP and 30% (v/v) TFE a near-UV CD
      spectrum approaches the native-like spectral features. Tryptophan fluorescence
      studies indicate the change in the environment of the tryptophan residues on the
      addition of HFIP and TFE to acid-unfolded papain. Maximum ANS binding occurs at
      13% (v/v) HFIP and 30% (v/v) TFE, suggesting a compact "molten globule"-like
      conformation with enhanced exposure of hydrophobic surface area. Acid-unfolded
      papain in presence of 13% (v/v) HFIP and 30% (v/v) TFE showed the recovery of
      enzymatic activity by 54 and 61%, respectively. Thermal stability of these states
      was assessed by changes in fluorescence emission maximum and absorbance at 292
      nm. Temperature-induced unfolding of papain at pH 2 was non-cooperative and the
      transition curves were biphasic in nature. Temperature-induced unfolding of HFIP
      and TFE-induced state was weakly cooperative in comparison to cooperative
      transition of native.

PMID- 15519300
TI  - Evidence that L1AD3, an apoptosis-inducing cyclic peptide, binds a leukemic T
      cell membrane protein receptor.
AB  - Human leukemic T-lymphocytes undergo extensive and rapid apoptosis in the
      presence of L1AD3, a small cyclic peptide derivative of cobra cardiotoxin. The
      first step in this process involves its binding to membranes of susceptible
      cells. By the use of a biotin "handle" synthetically incorporated at the N
      terminus of L1AD3, we show that binding is saturable and selective: normal human
      peripheral blood lymphocytes do not bind this peptide. Fluorescence resonance
      energy transfer experiments indicate that the binding sites are separated by at
      least 55 A. Loss of binding occurs if membrane proteins are enzymatically
      degraded, suggesting that L1AD3's target is a cell-membrane surface protein
      receptor. Finally, crosslinking of cyclic BTNL1AD3 peptide to a leukemic T-cell
      membrane surface receptor, as examined using a biotin-avidin blot, indicated a
      molecular weight of approximately 34,400.

PMID- 15519301
TI  - Enhancement of 7-methoxyresorufin O-demethylation activity of human cytochrome
      P450 1A2 by molecular breeding.
AB  - Alkylresorufins are model substrates for cytochrome P450 (P450) 1A2. The ability
      of human P450 1A2 to catalyze 7-methoxyresorufin O-demethylation was improved by
      screening of random mutant libraries (expressed in Escherichia coli) on the basis
      of 7-methoxyresorufin O-demethylation. After three rounds of mutagenesis and
      screening, the triple mutant E163K/V193M/K170Q yielded a kcat > five times faster
      than wild type P450 1A2 in steady-state kinetic analysis using either isolated
      membrane fractions or purified, reconstituted enzymes. The enhanced catalytic
      activity was not attributed to changes in substrate affinity. The kinetic
      hydrogen isotope effect of the triple mutant did not change from wild type enzyme
      and suggests that C-H bond cleavage is rate-limiting in both enzymes. Homology
      modeling, based on an X-ray structure of rabbit P450 2C5, suggests that the
      locations of mutated residues are not close to the substrate binding site and
      therefore that structural elements outside of this site play roles in changing
      the catalytic activity. This approach has potential value in understanding P450
      1A2 and generating engineered enzymes with enhanced catalytic activity.

PMID- 15519302
TI  - Plasma quercetin metabolites: structure-antioxidant activity relationships.
AB  - We studied quercetin metabolism in rats to determine the nature and conjugation
      positions on the resulting metabolites and to evaluate their contribution to the
      antioxidant activity of plasma. HPLC analysis showed that quercetin is primarily
      metabolized to glucuronides and sulfoglucuronides and, to a minor extent, to
      sulfates. ESI-MS/MS studies confirmed these results and indicate that the most
      plausible positions for glucuronidation and sulfation are the hydroxyl groups
      located at positions 5 and 7, excluding the 3'-OH and 4'-OH groups. Plasma
      antioxidant status was significantly higher in animals to which quercetin was
      administrated, suggesting that quercetin metabolites can retain some antioxidant
      activity when the o-catechol group does not undergo conjugation reactions. It was
      also shown that plasma quercetin metabolites could compete in vivo with other
      molecules for peroxynitrite. These results enabled the establishment of quercetin
      metabolite structure-antioxidant activity relationships and, hence, to understand
      their contribution for the antioxidant potential of plasma.

PMID- 15519303
TI  - Preferred orientations of LDL in vitreous ice indicate a discoid shape of the
      lipoprotein particle.
AB  - The structure of the human low-density lipoprotein (LDL) was analyzed in vitreous
      ice using cryo-electron microscopy (cryo-EM). In relatively thick cryo-EM
      preparations, random orientation of LDL particles produced various types of
      projections on the microscope screen, including circular projections with a high
      density ring and rectangular projections with two high-density bands. However, in
      especially thin preparations, preferred, non-random orientations of the LDL
      particle produced only circular projections of the lipoprotein structure. In
      preparations with high LDL concentrations, ordered two-dimensional arrays,
      including hexagonal arrangements of circular projections and short stacks of
      rectangular projections, were observed. These observations are consistent with a
      discoid shape of the LDL particle, and suggest that surface tension forces may
      influence orientation of the LDL disc in thin aqueous films. Face-on orientation
      of LDL in especially thin cryo-EM preparations may explain earlier difficulties
      in identifying discoid features of the lipoprotein particle, and illustrates that
      some caution is warranted when attempts are made to reconstruct the three
      dimensional structure of LDL from cryo-electron micrographs.

PMID- 15519305
TI  - Lipids in membrane protein structures.
AB  - This review describes the recent knowledge about tightly bound lipids in membrane
      protein structures and deduces general principles of the binding interactions.
      Bound lipids are grouped in annular, nonannular, and integral protein lipids. The
      importance of lipid binding for vertical positioning and tight integration of
      proteins in the membrane, for assembly and stabilization of oligomeric and
      multisubunit complexes, for supercomplexes, as well as their functional roles are
      pointed out. Lipid binding is stabilized by multiple noncovalent interactions
      from protein residues to lipid head groups and hydrophobic tails. Based on
      analysis of lipids with refined head groups in membrane protein structures,
      distinct motifs were identified for stabilizing interactions between the
      phosphodiester moieties and side chains of amino acid residues. Differences
      between binding at the electropositive and electronegative membrane side, as well
      as a preferential binding to the latter, are observed. A first attempt to
      identify lipid head group specific binding motifs is made. A newly identified
      cardiolipin binding site in the yeast cytochrome bc(1) complex is described.
      Assignment of unsaturated lipid chains and evolutionary aspects of lipid binding
      are discussed.

PMID- 15519307
TI  - Thermodynamics of lipid-peptide interactions.
AB  - This review is focused on peptide molecules which exhibit a limited solubility in
      the aqueous phase and bind to the lipid membrane from the aqueous medium. Surface
      adsorption, membrane insertion, and specific binding are usually accompanied by
      changes in the heat content of the system and can be measured conveniently with
      isothermal titration calorimetry, avoiding the necessity of peptide labeling. The
      driving forces for peptide adsorption and binding are hydrophobicity,
      electrostatics, and hydrogen bonding. An exclusively hydrophobic interaction is
      exemplified by the immunosuppressant drug cyclosporine A. Its insertion into the
      membrane can be described by a simple partition equilibrium X(b)=K(0)C(eq). If
      peptide and membrane are both charged, electrostatic interactions are dominant
      leading to nonlinear binding curves. The concentration of the peptide near the
      membrane interface can then be much larger than its bulk concentration.
      Electrostatic effects must be accounted for by means of the Gouy-Chapman theory
      before conventional binding models can be applied. A small number of peptides and
      proteins bind with very high affinity to a specific lipid species only. This is
      illustrated for the lantibiotic cinnamycin (Ro 09-0198) which forms a 1:1 complex
      with phosphatidyethanolamine with a binding constant of 10(8) M(-1). Membrane
      adsorption and insertion can be accompanied by conformational transitions
      facilitated, in part, by hydrogen bonding mechanisms. The two membrane-induced
      conformational changes to be discussed are the random coil-to-alpha-helix
      transition of amphipathic peptides and the random coil-to-beta-structure
      transition of Alzheimer peptides.

PMID- 15519306
TI  - Diversity and versatility of lipid-protein interactions revealed by molecular
      genetic approaches.
AB  - The diversity in structures and physical properties of lipids provides a wide
      variety of possible interactions with proteins that affect their assembly,
      organization, and function either at the surface of or within membranes. Because
      lipids have no catalytic activity, it has been challenging to define many of
      their precise functions in vivo in molecular terms. Those processes responsive to
      lipids are attuned to the native lipid environment for optimal function, but
      evidence that lipids with similar properties or even detergents can sometimes
      partially replace the natural lipid environment has led to uncertainty as to the
      requirement for specific lipids. The development of strains of microorganisms in
      which membrane lipid composition can be genetically manipulated in viable cells
      has provided a set of reagents to probe lipid functions. These mutants have
      uncovered previously unrecognized roles for lipids and provided in vivo
      verification for putative functions described in vitro. In this review, we
      summarize how these reagent strains have provided new insight into the function
      of lipids. The role of specific lipids in membrane protein folding and
      topological organization is reviewed. The evidence is summarized for the
      involvement of anionic lipid-enriched domains in the organization of amphitropic
      proteins on the membrane surface into molecular machines involved in DNA
      replication and cell division.

PMID- 15519308
TI  - Where sterols are required for endocytosis.
AB  - Sterols are essential membrane components of eukaryotic cells. Interacting
      closely with sphingolipids, they provide the membrane surrounding required for
      membrane sorting and trafficking processes. Altering the amount and/or structure
      of free sterols leads to defects in endocytic pathways in mammalian cells and
      yeast. Plasma membrane structures functioning in the internalization step in
      mammalian cells, caveolae and clathrin-coated pits, are affected by cholesterol
      depletion. Accumulation of improper plasma membrane sterols prevents
      hyperphosphorylation of a plasma membrane receptor in yeast. Once internalized,
      sterols still interact with sphingolipids and are recycled to the plasma membrane
      to keep an intracellular sterol gradient with the highest amount of free sterols
      at the cell periphery. Interestingly, cells from patients suffering from
      sphingolipid storage diseases show high intracellular amounts of free
      cholesterol. We propose that the balanced interaction of sterols and
      sphingolipids is responsible for protein recruitment to specialized membrane
      domains and their functionality in the endocytic pathway.

PMID- 15519309
TI  - How lipids affect the activities of integral membrane proteins.
AB  - The activities of integral membrane proteins are often affected by the structures
      of the lipid molecules that surround them in the membrane. One important
      parameter is the hydrophobic thickness of the lipid bilayer, defined by the
      lengths of the lipid fatty acyl chains. Membrane proteins are not rigid entities,
      and deform to ensure good hydrophobic matching to the surrounding lipid bilayer.
      The structure of the lipid headgroup region is likely to be important in defining
      the structures of those parts of a membrane protein that are located in the lipid
      headgroup region. A number of examples are given where the conformation of the
      headgroup-embedded region of a membrane protein changes during the reaction cycle
      of the protein; activities of such proteins might be expected to be particularly
      sensitive to lipid headgroup structure. Differences in hydrogen bonding potential
      and hydration between the headgroups of phosphatidycholines and
      phosphatidylethanolamines could be important factors in determining the effects
      of these lipids on protein activities, as well as any effects related to the
      tendency of the phosphatidylethanolamines to form a curved, hexagonal H(II)
      phase. Effects of lipid structure on protein aggregation and helix-helix
      interactions are also discussed, as well as the effects of charged lipids on ion
      concentrations close to the surface of the bilayer. Interpretations of lipid
      effects in terms of changes in protein volume, lipid free volume, and curvature
      frustration are also described. Finally, the role of non-annular, or 'co-factor'
      lipids, tightly bound to membrane proteins, is described.

PMID- 15519310
TI  - Bacterial osmosensing: roles of membrane structure and electrostatics in lipid
      protein and protein-protein interactions.
AB  - Bacteria act to maintain their hydration when the osmotic pressure of their
      environment changes. When the external osmolality decreases (osmotic downshift),
      mechanosensitive channels are activated to release low molecular weight osmolytes
      (and hence water) from the cytoplasm. Upon osmotic upshift, osmoregulatory
      transporters are activated to import osmolytes (and hence water). Osmoregulatory
      channels and transporters sense and respond to osmotic stress via different
      mechanisms. Mechanosensitive channel MscL senses the increasing tension in the
      membrane and appears to gate when the lateral pressure in the acyl chain region
      of the lipids drops below a threshold value. Transporters OpuA, BetP and ProP are
      activated when increasing external osmolality causes threshold ionic
      concentrations in excess of about 0.05 M to be reached in the proteoliposome
      lumen. The threshold activation concentrations for the OpuA transporter are
      strongly dependent on the fraction of anionic lipids that surround the
      cytoplasmic face of the protein. The higher the fraction of anionic lipids, the
      higher the threshold ionic concentrations. A similar trend is observed for the
      BetP transporter. The lipid dependence of osmotic activation of OpuA and BetP
      suggests that osmotic signals are transmitted to the protein via interactions
      between charged osmosensor domains and the ionic headgroups of the lipids in the
      membrane. The charged, C-terminal domains of BetP and ProP are important for
      osmosensing. The C-terminal domain of ProP participates in homodimeric coiled
      coil formation and it may interact with the membrane lipids and soluble protein
      ProQ. The activation of ProP by lumenal, macromolecular solutes at constant ionic
      strength indicates that its structure and activity may also respond to
      macromolecular crowding. This excluded volume effect may restrict the range over
      which the osmosensing domain can electrostatically interact. A simplified version
      of the dissociative double layer theory is used to explain the activation of the
      transporters by showing how changes in ion concentration could modulate
      interactions between charged osmosensor domains and charged lipid or protein
      surfaces. Importantly, the relatively high ionic concentrations at which
      osmosensors become activated at different surface charge densities compare well
      with the predicted dependence of 'critical' ion concentrations on surface charge
      density. The critical ion concentrations represent transitions in Maxwellian
      ionic distributions at which the surface potential reaches 25.7 mV for monovalent
      ions. The osmosensing mechanism is qualitatively described as an "ON/OFF switch"
      representing thermally relaxed and electrostatically locked protein
      conformations.

PMID- 15519311
TI  - Membrane proteins, lipids and detergents: not just a soap opera.
AB  - Studying membrane proteins represents a major challenge in protein biochemistry,
      with one of the major difficulties being the problems encountered when working
      outside the natural lipid environment. In vitro studies such as crystallization
      are reliant on the successful solubilization or reconstitution of membrane
      proteins, which generally involves the careful selection of solubilizing
      detergents and mixed lipid/detergent systems. This review will concentrate on the
      methods currently available for efficient reconstitution and solubilization of
      membrane proteins through the use of detergent micelles, mixed lipid/detergent
      micelles and bicelles or liposomes. We focus on the relevant molecular properties
      of the detergents and lipids that aid understanding of these processes. A
      significant barrier to membrane protein research is retaining the stability and
      function of the protein during solubilization, reconstitution and
      crystallization. We highlight some of the lessons learnt from studies of membrane
      protein folding in vitro and give an overview of the role that lipids can play in
      stabilizing the proteins.

PMID- 15519312
TI  - The protein-lipid interface: perspectives from magnetic resonance and crystal
      structures.
AB  - Lipid-protein interactions in membranes are dynamic, and consequently are well
      studied by magnetic resonance spectroscopy. More recently, lipids associated with
      integral membrane proteins have been resolved in crystals by X-ray diffraction,
      mostly at cryogenic temperatures. The conformation and chain ordering of lipids
      in crystals of integral proteins are reviewed here and are compared and
      contrasted with results from magnetic resonance and with the crystal structures
      of phospholipid bilayers. Various aspects of spin-label magnetic resonance
      studies on lipid interactions with single integral proteins are also reviewed:
      specificity for phosphatidylcholine, competition with local anaesthetics,
      oligomer formation of single transmembrane helices, and protein-linked lipid
      chains. Finally, the interactions between integral proteins and peripheral or
      lipid-linked proteins, as reflected by the lipid-protein interactions in double
      reconstitutions, are considered.

PMID- 15519313
TI  - Membrane fluidity and its roles in the perception of environmental signals.
AB  - Poikilothermic organisms are exposed to frequent changes in environmental
      conditions and their survival depends on their ability to acclimate to such
      changes. Changes in ambient temperature and osmolarity cause fluctuations in the
      fluidity of cell membranes. Such fluctuations are considered to be critical to
      the initiation of the regulatory reactions that ultimately lead to acclimation.
      The mechanisms responsible for the perception of changes in membrane fluidity
      have not been fully characterized. However, the analysis of genome-wide gene
      expression using DNA microarrays has provided a powerful new approach to studies
      of the contribution of membrane fluidity to gene expression and to the
      identification of environmental sensors. In this review, we focus on the
      mechanisms that regulate membrane fluidity, on putative sensors that perceive
      changes in membrane fluidity, and on the subsequent expression of genes that
      ensures acclimation to a new set of environmental conditions.

PMID- 15519314
TI  - Computer simulations of membrane proteins.
AB  - Computer simulations are rapidly becoming a standard tool to study the structure
      and dynamics of lipids and membrane proteins. Increasing computer capacity allows
      unbiased simulations of lipid and membrane-active peptides. With the increasing
      number of high-resolution structures of membrane proteins, which also enables
      homology modelling of more structures, a wide range of membrane proteins can now
      be simulated over time spans that capture essential biological processes. Longer
      time scales are accessible by special computational methods. We review recent
      progress in simulations of membrane proteins.

PMID- 15519315
TI  - The alignment, structure and dynamics of membrane-associated polypeptides by
      solid-state NMR spectroscopy.
AB  - Solid-state NMR spectroscopy is being developed at a fast pace for the structural
      investigation of immobilized and non-crystalline biomolecules. These include
      proteins and peptides associated with phospholipid bilayers. In contrast to
      solution NMR spectroscopy, where complete or almost complete averaging leads to
      isotropic values, the anisotropic character of nuclear interactions is apparent
      in solid-state NMR spectra. In static samples the orientation dependence of
      chemical shift, dipolar or quadrupolar interactions, therefore, provides angular
      constraints when the polypeptides have been reconstituted into oriented
      membranes. Furthermore, solid-state NMR spectroscopy of aligned samples offers
      distinct advantages in allowing access to dynamic processes such as topological
      equilibria or rotational diffusion in membrane environments. Alternatively, magic
      angle sample spinning (MAS) results in highly resolved NMR spectra, provided that
      the sample is sufficiently homogenous. MAS spinning solid-state NMR spectra allow
      to measure distances and dihedral angles with high accuracy. The technique has
      recently been developed to selectively establish through-space and through-bond
      correlations between nuclei, similar to the approaches well-established in
      solution-NMR spectroscopy.

PMID- 15519316
TI  - Lipids do influence protein function-the hydrophobic matching hypothesis
      revisited.
AB  - A topical review of the current state of lipid-protein interactions is given with
      focus on the physical interactions between lipids and integral proteins in lipid
      bilayer membranes. The concepts of hydrophobic matching and curvature stress are
      revisited in light of recent data obtained from experimental and theoretical
      studies which demonstrate that not only do integral proteins perturb the lipids,
      but the physical state of the lipids does also actively influence protein
      function. The case of the trans-membrane water-channel protein aquaporin GlpF
      from E. coli imbedded in lipid-bilayer membranes is discussed in some detail.
      Numerical data obtained from Molecular Dynamics simulations show on the one side
      that the lipid bilayer adapts to the channel by a hydrophobic matching condition
      which reflects the propensity of the lipid molecules for forming curved
      structures. On the other side, it is demonstrated that the transport function of
      the channel is modulated by the matching condition and/or the curvature stress in
      a lipid-specific manner.

PMID- 15519317
TI  - Do proteins facilitate the formation of cholesterol-rich domains?
AB  - Both biological and model membranes can exhibit the formation of domains. A brief
      review of some of the diverse methodologies used to identify the presence of
      domains in membranes is given. Some of these domains are enriched in cholesterol.
      The segregation of lipids into cholesterol-rich domains can occur in both pure
      lipid systems as well as membranes containing peptides and proteins. Peptides and
      proteins can promote the formation of cholesterol-rich domains not only by
      preferentially interacting with cholesterol and being sequestered into these
      regions of the membrane, but also indirectly as a consequence of being excluded
      from cholesterol-rich domains. The redistribution of components is dictated by
      the thermodynamics of the system. The formation of domains in a biological
      membrane is a consequence of all of the intermolecular interactions including
      those among lipid molecules as well as between lipids and proteins.

PMID- 15519318
TI  - On the role of lipid in colicin pore formation.
AB  - Insights into the protein-membrane interactions by which the C-terminal pore
      forming domain of colicins inserts into membranes and forms voltage-gated
      channels, and the nature of the colicin channel, are provided by data on: (i) the
      flexible helix-elongated state of the colicin pore-forming domain in the fluid
      anionic membrane interfacial layer, the optimum anionic surface charge for
      channel formation, and voltage-gated translocation of charged regions of the
      colicin domain across the membrane; (ii) structure-function data on the voltage
      gated K(+) channel showing translocation of an arginine-rich helical segment
      through the membrane; (iii) toroidal channels formed by small peptides that
      involve local participation of anionic lipids in an inverted phase. It is
      proposed that translocation of the colicin across the membrane occurs through
      minimization of the Born charging energy for translocation of positively charged
      basic residues across the lipid bilayer by neutralization with anionic lipid head
      groups. The resulting pore structure may consist of somewhat short, ca. 16
      residues, trans-membrane helices, in a locally thinned membrane, together with
      surface elements of inverted phase lipid micelles.

PMID- 15519319
TI  - Folding and assembly of beta-barrel membrane proteins.
AB  - Beta-barrel membrane proteins occur in the outer membranes of Gram-negative
      bacteria, mitochondria and chloroplasts. The membrane-spanning sequences of beta
      barrel membrane proteins are less hydrophobic than those of alpha-helical
      membrane proteins, which is probably the main reason why completely different
      folding and membrane assembly pathways have evolved for these two classes of
      membrane proteins. Some beta-barrel membrane proteins can be spontaneously
      refolded into lipid bilayer model membranes in vitro. They may also have this
      ability in vivo although lipid and protein chaperones likely assist with their
      assembly in appropriate target membranes. This review summarizes recent work on
      the thermodynamic stability and the mechanism of membrane insertion of beta
      barrel membrane proteins in lipid model and biological membranes. How lipid
      compositions affect folding and assembly of beta-barrel membrane proteins is also
      reviewed. The stability of these proteins in membranes is not as large as
      previously thought (<10 kcal/mol) and is modulated by elastic forces of the lipid
      bilayer. Detailed kinetic studies indicate that beta-barrel membrane proteins
      fold in distinct steps with several intermediates that can be characterized in
      vitro. Formation of the barrel is synchronized with membrane insertion and all
      beta-hairpins insert simultaneously in a concerted pathway.

PMID- 15519320
TI  - Protein-lipid interactions in membrane trafficking at the Golgi complex.
AB  - The integrated interplay between proteins and lipids drives many key cellular
      processes, such as signal transduction, cytoskeleton remodelling and membrane
      trafficking. The last of these, membrane trafficking, has the Golgi complex as
      its central station. Not only does this organelle orchestrates the biosynthesis,
      transport and intracellular distribution of many proteins and lipids, but also
      its own function and structure is dictated by intimate functional and physical
      relationships between protein-based and lipid-based machineries. These
      machineries are involved in the control of the fundamental events that govern
      membrane traffic, such as in the budding, fission and fusion of transport
      intermediates, in the regulation of the shape and geometry of the Golgi membranes
      themselves, and, finally, in the generation of "signals" that can have local
      actions in the secretory system, or that may affect other cellular systems. Lipid
      protein interactions rely on the abilities of certain protein domains to
      recognize specific lipids. These interactions are mediated, in particular,
      through the headgroups of the phospholipids, although a few of these protein
      domains are able to specifically interact with the phospholipid acyl chains.
      Recent evidence also indicates that some proteins and/or protein domains are more
      sensitive to the physical environment of the membrane bilayer (such as its
      curvature) than to its chemical composition.

PMID- 15519321
TI  - Nonbilayer lipids affect peripheral and integral membrane proteins via changes in
      the lateral pressure profile.
AB  - Nonbilayer lipids can be defined as cone-shaped lipids with a preference for
      nonbilayer structures with a negative curvature, such as the hexagonal phase. All
      membranes contain these lipids in large amounts. Yet, the lipids in biological
      membranes are organized in a bilayer. This leads to the question: what is the
      physiological role of nonbilayer lipids? Different models are discussed in this
      review, with a focus on the lateral pressure profile within the membrane. Based
      on this lateral pressure model, predictions can be made for the effect of
      nonbilayer lipids on peripheral and integral membrane proteins. Recent data on
      the catalytic domain of Leader Peptidase and the potassium channel KcsA are
      discussed in relation to these predictions and in relation to the different
      models on the function of nonbilayer lipids. The data suggest a general mechanism
      for the interaction between nonbilayer lipids and membrane proteins via the
      membrane lateral pressure.

PMID- 15519322
TI  - Synthesis of unnatural sugar nucleotides and their evaluation as donor substrates
      in glycosyltransferase-catalyzed reactions.
AB  - New unnatural sugar nucleotides, UDP-Fuc and CDP-Fuc were synthesized from fucose
      beta-1-phosphate and nucleotide monophosphates activated as morpholidates.
      Furthermore, a nucleotide analogue was prepared by phosphorylation of 1-(beta-D
      ribofuranosyl)cyanuric acid, itself obtained as a protected derivative by
      condensation of the persilylated derivative of cyanuric acid with 1-O-acetyl
      2,3,5-tri-O-benzoyl-beta-D-ribofuranose in 74% yield. This phosphate activated
      according to the same procedure was condensed with fucose-beta-1-phosphate,
      affording a new sugar nucleotide conjugate (NDP-Fuc) which was evaluated together
      with UDP-Fuc, CDP-Fuc and ADP-Fuc, as fucose donors in alpha-(1-->4/3)
      fucosyltransferase (FucT-III) catalyzed reaction. Fucose transfer could be
      observed with each of the donors and kinetic parameters were determined using a
      fluorescent acceptor substrate. Efficiency of the four analogues towards FucT-III
      was in the following order: UDP-Fuc=ADP-Fuc>NDP-Fuc>CDP-Fuc. According to the
      same strategy ADP-GlcNAc was prepared from AMP-morpholidate and N
      acetylglucosamine-alpha-1-phosphate; tested as a glucosaminyl donor towards
      Neisseria meningitidis N-acetylglucosaminyl transferase (LgtA), ADP-GlcNAc was
      recognized with 0.1% efficiency as compared with UDP-GlcNAc, the natural donor
      substrate.

PMID- 15519323
TI  - A facile approach to anhydrogalactosucrose derivatives from chlorinated sucrose.
AB  - Three new anhydrosucrose derivatives: 1,4:3,6-dianhydro-beta-D-fructofuranosyl 4
      chloro-4-deoxy-alpha-D-galactopyranoside (4), 1,4:3,6-dianhydro-beta-D
      fructofuranosyl 3,6-anhydro-4-chloro-4-deoxy-alpha-D-galactopyranoside (6) and
      1,6-dichloro-1,6-dideoxy-beta-D-fructofuranosyl-3,6-anhydro-4-chloro-4-deoxy
      alpha-D-galactopyranoside (8) were prepared from chlorinated sucrose. The
      structures of these anhydrides were confirmed by their (1)H and (13)C NMR
      spectra, ESIMS and elemental analysis. The crystal structures of 6 and the
      acetate of 4 (5) are presented. The relative reactivity of the chloromethyl
      groups towards S(N)2 reactions in 1,6-dichloro-1,6-dideoxy-beta-d-fructofuranosyl
      4,6-dichloro-4,6-dideoxy-alpha-D-galactopyranoside was found to be in order
      6>6'>1'.

PMID- 15519324
TI  - Structure of minor oligosaccharides from the lipopolysaccharide fraction from
      Pseudomonas stutzeri OX1.
AB  - A minor oligosaccharide fraction was isolated after complete de-acylation of the
      lipooligosaccharide extracted from Pseudomonas stutzeri OX1. The full structure
      of this oligosaccharide was obtained by chemical degradation, NMR spectroscopy
      and MALDI-TOF MS spectrometry. These experiments showed the presence of two novel
      oligosaccharides (OS1 and OS2): [structure: see text] where R=(S)-Pyr(-->4,6) in
      OS1 and alpha-Rha-(1-->3) in OS2. All sugars are D-pyranoses, except Rha, which
      is L-pyranose. Hep is L-glycero-D-manno-heptose, Kdo is 3-deoxy-D-manno-oct-2
      ulosonic acid, Pyr is pyruvic acid, P is phosphate.

PMID- 15519325
TI  - Structural investigation of a novel rhamnoglucogalactan isolated from the
      fruiting bodies of the fungus Hericium erinaceus.
AB  - A new heteropolysaccharide (HEP-1) was isolated from the fruiting bodies of
      Hericium erinaceus. It was estimated to have a molecular weight of 1.8x10(4) da
      and showed [alpha](D)(20) +129 (c 0.295, H(2)O). HEP-1 is composed of rhamnose,
      galactose, and glucose in the ratio of 1.19:3.81:1.00. Its structural features
      were investigated using composition analysis, methylation analysis, partial
      hydrolysis, and IR and NMR spectroscopy. The results showed that HEP-1 has a (1-
      >6)-linked alpha-d-galactopyranosyl backbone with branches that are composed of
      rhamnose and glucose attached to O-2.

PMID- 15519326
TI  - Succinyl and acetyl starch derivatives of a hybrid maize: physicochemical
      characteristics and retrogradation properties monitored by differential scanning
      calorimetry.
AB  - Starch isolated from a hybrid maize (8535-23) was chemically modified by
      succinylation and acetylation. No pronounced difference was observed between the
      X-ray pattern of native starch and modified starch samples, and the samples gave
      the characteristic A pattern of cereal starches. Onset temperature (T(o)), peak
      temperature (T(p)), concluding temperature (T(c)) and enthalpy of gelatinisation
      (DeltaH), reduced after succinylation and acetylation, but gelatinisation
      temperature range increased following starch modifications. Modifications reduced
      starch retrogradation.

PMID- 15519327
TI  - Structural parameters of amylopectin clusters and semi-crystalline growth rings
      in wheat starches with different amylose content.
AB  - Small-angle X-ray scattering (SAXS) and scanning electron microscopy (SEM) were
      used to investigate the internal structure of wheat starch granules with
      different amylose content. Different approaches were used for treatment
      (interpretation) of SAXS data to assess the values of structural parameters of
      amylopectin clusters and the size of crystalline and amorphous lamella in
      different wheat starches. The average values of the semi-crystalline growth rings
      thickness in starches have been determined and the relationship between
      structural characteristics and thermodynamic melting parameters is discussed.

PMID- 15519328
TI  - Preparation and antibacterial activity of chitosan nanoparticles.
AB  - Chitosan nanoparticles, such as those prepared in this study, may exhibit
      potential antibacterial activity as their unique character. The purpose of this
      study was to evaluate the in vitro antibacterial activity of chitosan
      nanoparticles and copper-loaded nanoparticles against various microorganisms.
      Chitosan nanoparticles were prepared based on the ionic gelation of chitosan with
      tripolyphosphate anions. Copper ions were adsorbed onto the chitosan
      nanoparticles mainly by ion-exchange resins and surface chelation to form copper
      loaded nanoparticles. The physicochemical properties of the nanoparticles were
      determined by size and zeta potential analysis, atomic force microscopy (AFM),
      FTIR analysis, and XRD pattern. The antibacterial activity of chitosan
      nanoparticles and copper-loaded nanoparticles against E. coli, S. choleraesuis,
      S. typhimurium, and S. aureus was evaluated by calculation of minimum inhibitory
      concentration (MIC) and minimum bactericidal concentration (MBC). Results show
      that chitosan nanoparticles and copper-loaded nanoparticles could inhibit the
      growth of various bacteria tested. Their MIC values were less than 0.25
      microg/mL, and the MBC values of nanoparticles reached 1 microg/mL. AFM revealed
      that the exposure of S. choleraesuis to the chitosan nanoparticles led to the
      disruption of cell membranes and the leakage of cytoplasm.

PMID- 15519329
TI  - Flexible chitin films: structural studies.
AB  - Chitin gels were transformed into thin, flexible chitin films with minimal
      dimensional shrinkage and maximum flexibility and thickness in the range of 25-80
      microm by a cold-press process. Solvent residue was removed by heating the films
      at 50 degrees C for 12 h, followed by rinsing in 95% ethanol. The crystallinity
      and mechanical properties of the flexible chitin films were found to be a
      function of the amount of shrinkage from the gel to the final film that was
      obtained. For 28-microm thick films with 30% shrinkage, transparency of up to 90%
      was found. X-ray diffractometry (XRD) showed that the number of diffraction peaks
      appearing at 2theta;=23 degrees and 2theta;=27 degrees became increasingly
      sharper with shrinkage. Topographical information obtained from scanning electron
      microscopy (SEM) and atomic force microscopy (AFM) attributed the structural
      morphology of the films to the formation of sub-microscopic micelles. Scanning
      transmission electron microscopy (STEM) showed that shrinkage resulted in coarser
      microstructure, affecting tensile properties, where the ductility and toughness
      were proportional to the amount of shrinkage. These flexible chitin films have
      potential as wound dressing materials.

PMID- 15519330
TI  - Vibrational circular dichroism of carbohydrate films formed from aqueous
      solutions.
AB  - Vibrational circular dichroism (VCD) spectra in the entire 2000-900 cm(-1) region
      have been recorded, for the first time, for films of carbohydrates prepared from
      aqueous solutions. Eight different carbohydrates, alpha-D-glucopyranosyl-(1-->4)
      D-glucose, cyclomaltohexaose, alpha-D-glucopyranosyl alpha-D-glucopyranoside,
      beta-D-glucopyranosyl-(1-->6)-D-glucose, beta-D-glucopyranosyl-(1-->4)-D-glucose,
      D-glucose, and both enantiomers of 6-deoxygalactose and of allose, were
      investigated. The VCD spectra obtained for films are found to be identical to the
      corresponding spectra obtained for aqueous solutions of carbohydrates. These
      measurements demonstrate several advantages of significant importance. The strong
      infrared absorption of water has prevented, in the past, the pursuit for routine
      applications of VCD in determining the structures of carbohydrates in aqueous
      solutions. This limitation is not present for film studies because water solvent
      is removed in the process of preparing the films. Also, strong infrared
      absorption of water at 1650 cm(-1) requires the use of very short-pathlength (6
      microm) cells for measurements on aqueous solutions. This requirement and
      concomitant inconveniences (such as laborious assembling of a demountable liquid
      cell or purchasing an expensive variable pathlength liquid cell) have been
      eliminated for film measurements. The removal of interfering water absorption in
      film studies resulted in higher light throughput and better signal-to-noise
      ratios for VCD measurements. Another point of significance is that the amount of
      carbohydrate sample required for VCD measurements on films is approximately one
      to two orders of magnitude smaller than that required for corresponding VCD
      measurements on aqueous solutions. Since carbohydrate samples can now be studied
      as films, VCD spectroscopy becomes much more broadly applicable for carbohydrates
      than previously believed. The present work, in combination with other film
      measurements in our laboratory, indicate that VCD studies on films can be used
      more generally, providing a convenient and powerful approach for probing
      structural information for biologically important compounds.

PMID- 15519331
TI  - Development of a digital video-microscopy technique to study lactose
      crystallisation kinetics in situ.
AB  - Polarised light microscopy was employed non-invasively to monitor lactose
      crystallisation from non-seeded supersaturated solutions in real time. Images
      were continuously recorded, processed and characterised by image analysis, and
      the results were compared with those obtained by refractometry. Three
      crystallisation temperatures (10, 20 and 30 degrees C) and three different levels
      of initial relative supersaturation (C/C(s)=1.95; 2.34; 3.15) were investigated.
      Induction times using the imaging technique proved to be substantially lower than
      those determined using refractive index. Lactose crystals were isolated digitally
      to determine geometrical parameters of interest, such as perimeter, diameter,
      area, roundness and Feret mean, and to derive crystal growth rates. Mean growth
      rates obtained for single crystals were fitted to a combined mass transfer model
      (R(2)=0.9766). The model allowed the effects of temperature and supersaturation
      on crystallisation rate to be clearly identified. It also suggested that, in this
      set of experiments, surface integration seemed to be the rate controlling step.
      It is believed that a similar experimental set-up could be implemented in a real
      food system to characterise a particular process where crystallisation control is
      of interest and where traditional techniques are difficult to implement.

PMID- 15519332
TI  - 1,5-Anhydroxylitol from leaves of Olea europaea.
AB  - 1,5-Anhydroxylitol, a compound never found previously in the vegetal kingdom was
      obtained from Olea europaea leaves in approximately 0.5-1% yield.

PMID- 15519333
TI  - The condition for dynamic stability.
AB  - The well-known condition for standing stability in static situations is that the
      vertical projection of the centre of mass (CoM) should be within the base of
      support (BoS). On the basis of a simple inverted pendulum model, an extension of
      this rule is proposed for dynamical situations: the position of (the vertical
      projection of) the CoM plus its velocity times a factor (square root l/g) should
      be within the BoS, l being leg length and g the acceleration of gravity. It is
      proposed to name this vector quantity 'extrapolated centre of mass position'
      (XcoM). The definition suggests as a measure of stability the 'margin of
      stability' b, the minimum distance from XcoM to the boundaries of the BoS. An
      alternative measure is the temporal stability margin tau, the time in which the
      boundary of the BoS would be reached without intervention. Some experimental data
      of subjects standing on one or two feet, flatfoot and tiptoe, are presented to
      give an idea of the usual ranges of these margins of stability. Example data on
      walking are also presented.

PMID- 15519334
TI  - Validity of procedures involved in ultrasound-based measurement of human
      plantarflexor tendon elongation on contraction.
AB  - Ultrasonography is becoming increasingly popular for studying the tensile
      behaviour of in vivo human tendons through elongation measurements during
      isometric contraction. For the plantarflexor tendons specifically, which receive
      much attention due to their functional role in locomotion, elongations are
      conventionally measured by fixing the scanning probe on the calf. Elongation
      corrections are also made to account for artifactual ankle rotations during the
      isometric test, by assuming that these occur round the tibio-talar joint axis, as
      is the case for passive ankle plantarflexion-dorsiflexion rotations. The present
      work was set out to examine the validity of these procedures. The displacement of
      the calcaneum, a skin marker on the calf, and the gastrocnemius myotendinous
      junction, were measured from rest to maximum isometric voluntary plantarflexion
      contraction (MVC) in six men by using ultrasound probes mounted on externally
      fixed points (active test). A passive ankle plantarflexion rotation equal in
      magnitude to that recorded during MVC was then performed (passive test). In the
      active test, the calcaneum and the skin marker shifted in the proximo-distal
      direction by approximately 13 mm. Moreover, the calcaneal displacements in the
      active and passive tests took place round different rotational axes, as indicated
      by a calcaneal displacement difference of approximately 10 mm between the two
      tests. These effects resulted in underestimating by 35% the actual elongation of
      the gastrocnemius tendon when following the currently suggested procedures. The
      present results directly invalidate the procedures conventionally followed for
      assessing the tensile response of the human plantarflexor tendons with
      ultrasonography.

PMID- 15519335
TI  - The intra-push velocity profile of the over-ground racing wheelchair sprint
      start.
AB  - The aim of this study was to analyse the first six pushes of a sprint start in
      over-ground racing wheelchair propulsion. One international male wheelchair
      athlete (age=28 years; body mass=60.6 kg; racing classification=T4) performed
      maximal over-ground sprint trials, over approximately 10 m, in his own racing
      wheelchair fitted with a velocometer. Each trial was filmed at 200 Hz using a
      "Pan and Tilt" system. Eight trials were manually digitised at 100 Hz. Raw co
      ordinate data were smoothed and differentiated using a quintic spline routine.
      Across the period from pushes one to six the duration of each push cycle
      decreased (0.82+/-0.02-0.45+/-0.01 s) with the mean duration of the propulsive
      phase decreasing from 0.62+/-0.02 to 0.21+/-0.01 s and the recovery phase
      increasing from 0.20+/-0.01 to 0.24+/-0.02 s. The push-rim was contacted
      progressively closer to top dead centre and released progressively closer to
      bottom dead centre with each push. The data indicate that peak velocity occurred
      after release. The main findings of this study support the observation that
      racing wheelchair sprint propulsion is a complex form of locomotion and cannot be
      described accurately by using just the established definitions of a propulsive
      and a recovery phase.

PMID- 15519336
TI  - Analysis of forces of ACL reconstructions at the tunnel entrance: is tunnel
      enlargement a biomechanical problem?
AB  - Bone tunnel enlargement is a common phenomenon following reconstruction of the
      anterior cruciate ligament (ACL). Biomechanical and biological factors have been
      reported as potential causes of this problem. However, there is no analysis of
      forces between the graft and bone, as the graft changes direction at the bone
      tunnel entrance. The purpose of this study was to study these 'redirecting
      forces'. Magnetic resonance images of 10 patients with an ACL reconstruction
      (age: 26+/-6.8 years) were used to determine the angle between graft and drill
      holes. Vector analysis was used to calculate the direction and magnitude of the
      perpendicular component of the force between the bone tunnel and the graft at the
      entrance of the bone tunnel. Force components were projected into the
      radiographically important sagittal and coronal planes. Tension of ACL
      reconstructions was recorded during passive knee motion in 10 cadaveric knee
      experiments (age: 28.9+/-10.6 years) and the tension multiplied with the force
      component for each plane. Results are reported for the coronal and sagittal
      planes, respectively: For -10 degrees of extension, the percentages of graft
      tension were determined to be 17+/-7 (max: 26; min: 7%) and 26+/-9 (max: 39; min:
      16%) for the tibia. They were 59+/-6 (max: 66; min: 48%) and 99+/-1 (max: 1.00;
      min: 99%) for the femur. Force components were 14.68+/-6.54 and 25.73+/-12.96 N
      for the tibial tunnel. For the femoral tunnel, they were 52.48+/-19.03 and
      90.77+/-32.06 N. Percentages of graft tension and force components were
      significantly higher for the femoral tunnel compared with the tibial tunnel.
      Moreover, in the sagittal direction, force components for the femoral tunnel were
      significantly higher compared with the coronal plane (Wilcoxon test, p < 0.01).
      The differences in force components calculated in this study corresponds with the
      amount of tunnel enlargement in the radiographic planes in the literature
      providing evidence that biomechanical forces play a key role in postoperative
      tunnel expansion.

PMID- 15519337
TI  - Effects of helium-oxygen mixtures on endotracheal tubes: an in vitro study.
AB  - QUESTION: To determine flow pattern and critical Reynolds numbers in endotracheal
      tubes submitted to different helium-oxygen mixtures under laboratory conditions.
      MATERIALS AND METHODS: Flow-pressure relationships were performed for seven
      endotracheal tubes (rectilinear position, entry length applied) with distal end
      open to atmosphere (predicted internal diameters: 6-9 mm). Nine helium-oxygen
      mixtures were tested, with FIHe varying from zero to 0.78 (increment: 10%). Nine
      flows were tested, with rates varying from 0.25 to 1.60 l s(-1) (increment: 0.15
      l s(-1)). Gas flow resistance was calculated, and for each endotracheal tube, a
      Moody diagram was realised. Flow regime and critical Reynolds numbers were then
      determined (fully established laminar, nonestablished laminar, smooth turbulent,
      or rough). RESULTS: Even low concentration of helium in inspiratory mixture
      reduces endotracheal tubes resistance. Effect is maximal for high flows, small
      tube and high FIHe. Critical Reynolds numbers are inversely correlated to tube
      diameter. ANSWER: Under laboratory conditions, flow pattern in endotracheal tubes
      varies from fully established laminar to rough. Knowledge of the critical
      Reynolds numbers allows correct application of fluid mechanic formula when
      studying tube or gaseous mixture effects on respiratory mechanisms.

PMID- 15519338
TI  - On the use of a patient-specific rapid-prototyped model to simulate the response
      of the human head to impact and comparison with analytical and finite element
      models.
AB  - Every year, thousands of fatalities result from head injuries, the majority of
      which are sustained in automotive accidents. In this paper, an experimental study
      of the response of the human head to impact is presented. A rapid prototyped
      model of a human head was generated based on high-resolution magnetic resonance
      imaging (MRI) scan data. The physical model was subjected to low velocity impacts
      using a metallic pendulum and a sensitivity study was performed to explore the
      influence of various parameters, including mass and velocity of the impactor, on
      the response. The experimental response characteristics are compared with
      predictions from an analytical model as well as with numerical predictions from
      finite element (FE) models generated from the same MRI data set. The results from
      the experimental tests closely match those predicted by both the analytical and
      the FE models and thus provide us with substantive corroboration of all three
      approaches. The remarkable agreement obtained between the measured response
      characteristics of rapid-prototyped skulls and numerical (FE) models obtained
      from in vivo MRI data clearly demonstrates the potential use of rapid-prototyping
      to generate experimental models for head impact studies, and, more generally, for
      the study of the response of complex bio-structures to loading. In addition, the
      quantitative and qualitative accuracy of the predictions from the analytical
      model is clearly demonstrated by the FE and experimental corroboration. In
      particular, the analytical prediction that, as impact mass drops the impact
      duration becomes increasingly short, appears to be substantiated, which has
      important implications for the onset of high pressure and shear strain gradients
      in the brain with potentially deleterious effects.

PMID- 15519339
TI  - Automated classification of peripheral distal by-pass geometries reconstructed
      from medical data.
AB  - Abnormal haemodynamic conditions are implicated in the development of anastomotic
      myointimal hyperplasia (MIH). However, these conditions are difficult to
      determine in vivo, prompting research using ex vivo idealised models. To relate
      the understanding gained in idealised geometries to anatomically correct
      conditions we have investigated a reproducible approach to classify in vivo
      distal graft anastomoses and their inter-patient variability. In vivo distal
      anastomotic geometries were acquired by magnetic resonance (MR) angiography from
      13 patients who had undergone infrageniculate autologous venous by-pass surgery.
      On average, the images were acquired 2 weeks post-operatively. Five patients also
      underwent repeat examinations 2 to 7 weeks later. For each geometry, the surface
      of the arterial lumen is represented by the zero level set of an implicit
      function constructed from radial basis functions that minimise curvature. The
      three-dimensional binary image created from the interpolated surface is processed
      using a skeletonisation algorithm to obtain the centreline of each branch in the
      geometry. This allows for the measurement of the branching angles between
      straight line approximations of the centrelines of each vessel, averaging them
      over a characteristic length of each anastomosis. The main finding in the
      application of the proposed classification methodology to this set of patients is
      that the spectrum of anastomoses can be reduced to a small subset of cases
      characterised by two angles: the angle between the graft and the plane of the
      host artery and the angle between the graft and the proximal branch of the
      artery.

PMID- 15519340
TI  - The fixion proximal femur nailing system: biomechanical properties of the nail
      and a cadaveric study.
AB  - The treatment of choice for early mobilization of hip fracture is surgery, which
      traditionally employs side plates and screws or intramedullary nails. We examined
      the biomechanical properties of a new proximal femoral nail system. The new
      expandable Fixion proximal femur nailing (PFN) system, made of stainless-steel
      alloy, consists of a nail, a peg and an anti-rotation pin. Upon positioning, the
      nail and peg are expanded to their maximal diameter. The current biomechanical
      study investigated: nail bending strength and stiffness, fatigue properties and
      hip peg strength. A cadaveric study that determined the effect of the expandable
      peg on the femoral head included subsidence testing, pull and torsion testing and
      intra-osseous pressure (IOP) measurements before and after expansion.
      Biomechanical properties of the new nail met ASTM F384 guideline requirements.
      The cadaver study yielded equivalent results for the pullout test between the peg
      and the hip screw, but found the peg superior in the torsion strength test. IOP
      during peg insertion and expansion was substantially lower than the threshold
      pressure that causes avascular necrosis. The biomechanical tests found the new
      system to be safe and able to provide good abutment of the nail to the bone. We
      conclude that the Fixion PFN system proved to be an effective proximal femur
      fracture fixation device.

PMID- 15519341
TI  - Collagen fibril diameter distribution does not reflect changes in the mechanical
      properties of in vitro stress-deprived tendons.
AB  - The purpose of this study was to determine if an association exists between the
      tensile properties and the collagen fibril diameter distribution in in vitro
      stress-deprived rat tail tendons. Rat tail tendons were paired into two groups of
      21 day stress-deprived and 0 time controls and compared using transmission
      electron microscopy (n = 6) to measure collagen fibril diameter distribution and
      density, and mechanical testing (n =6) to determine ultimate stress and tensile
      modulus. There was a statistically significant decrease in both ultimate tensile
      strength (control: 17.95+/-3.99 MPa, stress-deprived: 6.79+/-3.91 MPa) and
      tensile modulus (control: 312.8+/-89.5 MPa, stress-deprived: 176.0+/-52.7 MPa) in
      the in vitro stress-deprived tendons compared to controls. However, there was no
      significant difference between control and stress-deprived tendons in the number
      of fibrils per tendon counted, mean fibril diameter, mean fibril density, or
      fibril size distribution. The results of this study demonstrate that the decrease
      in mechanical properties observed in in vitro stress-deprived rat tail tendons is
      not correlated with the collagen fibril diameter distribution and, therefore, the
      collagen fibril diameter distribution does not, by itself, dictate the decrease
      in mechanical properties observed in in vitro stress-deprived rat tail tendons.

PMID- 15519342
TI  - Unconfined creep compression of chondrocytes.
AB  - The study of single cell mechanics offers a valuable tool for understanding
      cellular milieus. Specific knowledge of chondrocyte biomechanics could lead to
      elucidation of disease etiologies and the biomechanical factors most critical to
      stimulating regenerative processes in articular cartilage. Recent studies in our
      laboratory have suggested that it may be acceptable to approximate the shape of a
      single chondrocyte as a disc. This geometry is easily utilized for generating
      models of unconfined compression. In this study, three continuum mechanics models
      of increasing complexity were formulated and used to fit unconfined compression
      creep data. Creep curves were obtained from middle/deep zone chondrocytes (n =
      15) and separately fit using the three continuum models. The linear elastic solid
      model yielded a Young's modulus of 2.55+/-0.85 kPa. The viscoelastic model
      (adapted from the Kelvin model) generated an instantaneous modulus of 2.47+/-0.85
      kPa, a relaxed modulus of 1.48+/-0.35 kPa, and an apparent viscosity of 1.92+/
      1.80 kPa-s. Finally, a linear biphasic model produced an aggregate modulus of
      2.58+/-0.87 kPa, a permeability of 2.57 x 10(-12)+/-3.09 m(4)/N-s, and a
      Poisson's ratio of 0.069+/-0.021. The results of this study demonstrate that
      similar values for the cell modulus can be obtained from three models of
      increasing complexity. The elastic model provides an easy method for determining
      the cell modulus, however, the viscoelastic and biphasic models generate
      additional material properties that are important for characterizing the
      transient response of compressed chondrocytes.

PMID- 15519343
TI  - Mechanics of the taper integrated screwed-in (TIS) abutments used in dental
      implants.
AB  - The tapered implant-abutment interface is becoming more popular due to the
      mechanical reliability of retention it provides. Consequently, understanding the
      mechanical properties of the tapered interface with or without a screw at the
      bottom has been the subject of a considerable amount of studies involving
      experiments and finite element (FE) analysis. This paper focuses on the tapered
      implant-abutment interface with a screw integrated at the bottom of the abutment.
      The tightening and loosening torques are the main factors in determining the
      reliability and the stability of the attachment. Analytical formulas are
      developed to predict tightening and loosening torque values by combining the
      equations related to the tapered interface with screw mechanics equations. This
      enables the identification of the effects of the parameters such as friction,
      geometric properties of the screw, the taper angle, and the elastic properties of
      the materials on the mechanics of the system. In particular, a relation between
      the tightening torque and the screw pretension is identified. It was shown that
      the loosening torque is smaller than the tightening torque for typical values of
      the parameters. Most of the tightening load is carried by the tapered section of
      the abutment, and in certain combinations of the parameters the pretension in the
      screw may become zero. The calculations performed to determine the loosening
      torque as a percentage of tightening torque resulted in the range 85-137%,
      depending on the values of taper angle and the friction coefficient.

PMID- 15519344
TI  - Tendon properties in interleukin-4 and interleukin-6 knockout mice.
AB  - Cytokines are known to play an important role in normal tendon development,
      function, and maintenance through interactions with fibroblasts and extracellular
      matrix proteins. However, the role of interleukins on normal tendon activity
      remains poorly understood. Previous studies that have researched the role of
      specific cytokines by exogenously applying them have often reported conflicting
      results. Therefore, a knockout mouse model was used to investigate the role of
      interleukins 4 and 6 on normal tendon organizational and biomechanical
      properties. It was hypothesized that interleukin-6 knockout (IL6 -/-) mice will
      display more organized collagen orientation and greater cross-sectional area and
      mechanical properties when compared to that of control mice. In addition,
      interleukin-4 knockout (IL4 -/-) mice will display the most disorganized collagen
      orientation and lowest cross-sectional area and mechanical properties. As
      hypothesized, IL6 -/- mice show a trend towards lower angular deviation (more
      organized) (p<0.1) when compared to IL4 -/- mice. In addition, the IL6 -/- mice
      show a trend towards a higher percent relaxation (p<0.1) and a significantly
      higher modulus (p<0.01) when compared to CTL and IL4 -/- mice. Unexpectedly, the
      IL6 -/- mice exhibited no significant differences in collagen fiber distribution
      and maximum stress from the other groups and actually had a smaller cross
      sectional area than CTL mice (p<0.1). This study supports transgenic mice as an
      animal model for investigating how cytokines affect normal tendon properties. In
      addition, this study demonstrates that interleukins may play an important role in
      tendon development, function, and maintenance.

PMID- 15519345
TI  - A new method for estimating joint parameters from motion data.
AB  - Joint centers and axes of rotation (joint parameters) are central to all branches
      of movement analysis. In gait analysis, the standard protocol used to determine
      hip and knee joint parameters is prone to errors arising from palpation,
      anthropometric regression equations, and misplaced alignment devices. Several
      alternative methods have been proposed, but to date none have been shown to be
      accurate and reliable enough for use in the clinical setting. This article
      describes a new method for joint parameter estimation. The new method can be
      summarized as follows: (i) the motions of two adjacent segments spanning a single
      joint are tracked, (ii) the axis of rotation between every pair of observed
      segment configurations is computed, (iii) the most likely intersection of all
      axes (effective joint center) and most likely orientation of the axes (effective
      joint axis) is found. Initial validation of the method was conducted on a hinged
      mechanical analog and a single healthy adult subject. For the analog, the center
      was found to be within 3.8 mm of the geometric center and 2.0 degrees of the
      geometric axis (standard deviation). For the adult subject, hip centers varied on
      the order of 1-3 mm, knee centers by 3-9 mm, and knee axes by 2.0 degrees. The
      results suggest that the new method is an objective, precise, and practical
      alternative to the standard clinical approach.

PMID- 15519346
TI  - On the mechanism of cell lysis by deformation.
AB  - In this study, we identify the extent of deformation that causes cell lysis using
      a simple technique where a drop of cell suspension is compressed by two flat
      plates. The viability of human prostatic adenocarcinoma PC-3 cells in solutions
      of various concentrations of NaCl is determined as a function of the gap size
      between the plates. The viability declines with decreasing gap size in the
      following order: 700 mM >150 mM >75 mM NaCl. This is considered to be due to the
      difference in cell size, which is caused by the osmotic volume change before
      deformation; cell diameter becomes smaller in a solution of higher NaCl
      concentration, which appears to increase the survival ratio in a given gap size.
      The deformation-induced decrease in cell viability is correlated with the cell
      surface strain, which is dependent on the increase in surface area, irrespective
      of NaCl concentration. In addition, the treatment of cells with cytochalasin D
      results in the disappearance of cortical actin filaments and a marked drop in the
      viability, indicating that cell lysis is closely related to the deformation of
      the cytoskeleton.

PMID- 15519347
TI  - The influence of the oscillation angle and the neck anteversion of the prosthesis
      on the cup safe-zone that fulfills the criteria for range of motion in total hip
      replacements. The required oscillation angle for an acceptable cup safe-zone.
AB  - A normal hip joint has more than 120 degrees flexion. The reduced range of motion
      (ROM) of total hip arthroplast leads to frequent prosthetic impingement,
      subluxation and dislocation. Prosthetic impingement may be more serious for metal
      on-metal and ceramic-on-ceramic total hip prosthesis (THP). A larger oscillation
      angle of THP (OsA) and proper cup and neck positions make a larger theoretical
      ROM of a patient's artificial hip joint. But what OsA is required and what range
      of cup positions is kinetically accepted are not clearly understood. A ROM of
      more than 120 degrees flexion, 45 degrees internal-rotation at 90 degrees
      flexion, 30 degrees extension and 40 degrees external-rotation was defined as
      severe criteria for an acceptable ROM. Theoretical cup safe-zones were created
      that fulfill the severe criteria of ROM for (OsA=110 degrees , 120 degrees , 135
      degrees ) by the mathematical formulas. The size of the cup safe-zone mainly
      depends on the size of the OsA. There is no cup safe-zone for 110 degrees OsA, an
      extremely small safe-zone for 120 degrees OsA and an acceptable safe-zone for 135
      degrees OsA. Each THP has its own OsA, because OsA is the function of head and
      neck diameter and cup design. More than 135 degrees OsA enlarges the safe-zone of
      the prosthetic position, so it extends the acceptable range of error that
      surgeons cannot avoid completely. However, few THPs with more than 135 degrees
      OsA are currently clinically available. Both surgeons and manufacturers must
      realize that OsA is as essential as cup and neck orientations for ROM.

PMID- 15519348
TI  - The effect of muscle loading on the simulation of bone remodelling in the
      proximal femur.
AB  - A large number of finite element analyses of the proximal femur rely on a
      simplified set of muscle and joint contact loads to represent the boundary
      conditions of the model. In the context of bone remodelling analysis around hip
      implants, muscle loading affects directly the spatial distribution of the
      remodelling signal. In the present study we performed a sensitivity analysis on
      the effect of different muscle loading configurations on the outcome of the bone
      remodelling simulation. An anatomical model of the femur with the implanted stem
      in place was constructed using the CT data of the Visible Human Project dataset
      of the National Institute of Health. The model was loaded with three muscle force
      configurations with increasing level of complexity. A strain adaptive remodelling
      rule was employed to simulate the post-operative bone changes around the implant
      stem and the results of the simulation were assessed quantitatively in terms of
      the bone mineral content changes in 18 periprosthetic regions of interest. The
      results showed considerable differences in the amount of bone loss predicted
      between the three cases. The simplified models generally predicted more
      pronounced bone loss. Although the overall remodelling patterns observed were
      similar, the bone conserving effect of additional muscle forces in the vicinity
      of their areas of attachment was clear. The results of this study suggest that
      the loading configuration of the FE model does play an important role in the
      outcome of the remodelling simulation.

PMID- 15519349
TI  - Tensile and compressive stress yield criteria for cancellous bone.
AB  - Experimentally based isotropic tensile and compressive strain yield criteria for
      cancellous bone are shown to imply tensile and compressive stress yield criteria,
      respectively. In particular, it is deduced that the directional variation of
      uniaxial yield stress is proportional to the one of Young's modulus. The obtained
      tensile and compressive stress yield criteria, in turn, imply information about
      the total stress yield criterion for cancellous bone.

PMID- 15519350
TI  - Factors influencing performance in the Hecht vault and implications for
      modelling.
AB  - This paper investigated the factors that influence Hecht vault performance and
      assessed the level of model complexity required to give an adequate
      representation of vaulting. A five-segment planar simulation model with a visco
      elastic shoulder joint and a torque generator at the shoulder joint was used to
      simulate the contact phase in vaulting. The model was customized to an elite
      gymnast by determining subject-specific segmental inertia and joint torque
      parameters. The simulation model was matched to a performance of the Hecht vault
      by varying the visco-elastic characteristics of the shoulders and the arm-horse
      interface and the activation time history of the shoulder torque generator until
      the best match was found. Perturbing the matching simulation demonstrated that
      appropriate initial kinematics are necessary for a successful performance. Fixing
      the hip and knee angles at their initial values had a small effect with 3 degrees
      less rotation. Applying shoulder torque during the contact phase also had a small
      effect with only a 7 degrees range in landing angles. Excluding the hand segment
      from the model was found to have a moderate effect with 15 degrees less rotation
      and the time of contact reduced by 38%. Removing shoulder elasticity resulted in
      50 degrees less rotation. The use of a five-segment simulation model confirmed
      that the use of shoulder torque plays a minor role in vaulting performance and
      that having appropriate initial kinematics at touchdown is essential. However,
      factors such as shoulder elasticity and the hands which have previously been
      ignored also have a substantial influence on performance.

PMID- 15519351
TI  - Method of testing very soft biological tissues in compression.
AB  - Mechanical properties of very soft tissues, such as brain, liver, kidney and
      prostate have recently joined the mainstream research topics in biomechanics.
      This has happened in spite of the fact that these tissues do not bear mechanical
      loads. The interest in the biomechanics of very soft tissues has been motivated
      by the developments in computer-integrated and robot-aided surgery--in
      particular, the emergence of automatic surgical tools and robots-as well as
      advances in virtual reality techniques. Mechanical testing of very soft tissues
      provides a formidable challenge for an experimenter. Very soft tissues are
      usually tested in compression using an unconfined compression set-up, which
      requires ascertaining that friction between sample faces and stress-strain
      machine platens is close to zero. In this paper a more reliable method of testing
      is proposed. In the proposed method top and bottom faces of a cylindrical
      specimen with low aspect ratio are rigidly attached to the platens of the stress
      strain machine (e.g. using surgical glue). This arrangement allows using a no
      slip boundary condition in the analysis of the results. Even though the state of
      deformation in the sample cannot be treated as orthogonal the relationships
      between total change of height (measured) and strain are obtained. Two important
      results are derived: (i) deformed shape of a cylindrical sample subjected to
      uniaxial compression is independent on the form of constitutive law, (ii)
      vertical extension in the plane of symmetry lambda(z) is proportional to the
      total change of height for strains as large as 30%. The importance and relevance
      of these results to testing procedures in biomechanics are highlighted.

PMID- 15519352
TI  - Dynamic shear stress in parallel-plate flow chambers.
AB  - An in vitro model using a parallel-plate fluid flow chamber is supposed to
      simulate in vivo fluid shear stresses on various cell types exposed to dynamic
      fluid flow in their physiological environment. The metabolic response of cells in
      vitro is associated with the wall shear stress. However, parallel-plate flow
      chambers have not been characterized for dynamic fluid flow experiments. We use a
      dimensionless ratio h / lambda(v), in determining the exact magnitude of the
      dynamic wall shear stress, with its oscillating components scaled by a shear
      factor T. It is shown that, in order to expose cells to predictable levels of
      dynamic fluid shear stress, two conditions have to be met: (1) h / lambda(v) < 2,
      where h is the distance between the plates and lambda(v) is the viscous
      penetration depth; and (2) f(0) < f(c) / m, where the critical frequency f(c) is
      the upper threshold for this flow regime, m is the highest harmonic mode of the
      flow, and f(0) is the fundamental frequency of fluid flow.

PMID- 15519353
TI  - The video technique developed for measuring epicardial strains on guinea pig's
      left ventricle.
AB  - Single-plain video used for measurements of epicardial strains is a technique
      that yields minor interference with the studied mechanical properties of the
      ventricle. Due to its low temporal resolution, the existing technique is,
      however, not appropriate for small animals. We questioned whether the technique
      could be improved enough to cope with higher heart rates and miniaturization
      necessary for experiments on rats, mice and guinea pigs. Therefore, we developed
      a high-speed video system and used it for measuring epicardial strains in guinea
      pig hearts in situ with the open chest. The improvement was achieved in video
      hardware (camera: Dalsa D6-0256; framegraber: EPIX PIXCI D32) and software, the
      markers (glowing acrylate crystals; diameter approximately 0.15 mm) and
      illumination (UVA light, OSRAM L). Three markers were attached onto the
      epicardium in the equatorial region of the left ventricular free wall, 1.5 mm
      apart, with fibrin glue. From their coordinates, we calculated two-dimensional
      finite strains with end diastole as the reference point. The accuracy of the
      displacement measurement of the technique and the error introduced by approximate
      visual estimation of the left ventricle coordinate system were evaluated. The
      accuracy of the displacement measurement was +/-1.6 microm and the temporal
      resolution was 2 ms. Error due to approximate coordinate system orientation was
      +/-3% of the strain amplitude. The typical amplitude of strains was -0.06, -0.11
      and 0.04 in circumferential, axial direction and in-plane shear, respectively.
      The improvements enable us to perform physiologically relevant measurements of
      epicardial deformations on guinea pig heart.

PMID- 15519354
TI  - Baseline measures are altered in biomechanical studies.
AB  - The purpose of this investigation was to examine if baseline measures are altered
      between conditions in biomechanical studies and to determine the need for
      baseline measurements in biomechanics. Ten runners were asked to run at varying
      speeds and obstacle heights. Baseline measures were acquired between all
      conditions. Right lower extremity kinematic and kinetic data were collected for
      all baseline trials and evaluated by both a group and a single subject analysis.
      The group analysis revealed significant differences between baselines only for
      the obstacle perturbation. The single subject analysis indicated that baseline
      measures are altered in a greater degree for kinematics than kinetics. These
      findings suggested that baseline measures are altered between conditions in
      biomechanical studies, and they should be used when a repeated measures or a
      single subject experimental design is being utilized.

PMID- 15519355
TI  - An articular cartilage contact model based on real surface geometry.
AB  - Abnormal, excessive stresses acting on articular joint surfaces are speculated to
      be one of the causes for joint degeneration. However, articular surface stresses
      have not been studied systematically, since it is technically difficult to
      measure in vivo contact areas and pressures in dynamic situations. Therefore, we
      implemented a numerical model of articular surface contact using accurate surface
      geometries. The model was developed for the cat patellofemoral joint. We
      demonstrated that small misalignments of the patella relative to the femur change
      the joint contact mechanics substantially for a given external load. These
      results suggest that misalignment might be studied as one of the factors causing
      articular cartilage disorder and joint degeneration.

PMID- 15519356
TI  - A CFD level-set method for soft tissue growth: theory and fundamental equations.
AB  - A level-set method, specifically conceived for the case of soft organic tissue
      growth from feeding solutions, is introduced and described in detail. The model
      can handle the morphological evolution of the organic specimen under the
      influence of external convection (fluid-dynamics of the bioreactor). The
      analogies and differences between this technique and a previous volume of
      fraction method are discussed pointing out advantages and limitations of both
      formulations.

PMID- 15519357
TI  - On the elastic properties of arteries, by Stephanis, C.G., et al., 2000.; Journal
      of Biomechanics 36, 1727-1731.

PMID- 15519359
TI  - Toward a comprehensive model for induced endoreduplication.
AB  - Both the biological significance and the molecular mechanism of endoreduplication
      (END) have been debated for a long time by cytogeneticists and researchers into
      cell cycle enzymology and dynamics alike. Mainly due to the fact that a wide
      variety of agents have been reported as able to induce endoreduplication and the
      diversity of cell types where it has been described, until now no clear or unique
      mechanism of induction of this phenomenon, rare in animals but otherwise quite
      common in plants, has been proposed. DNA topoisomerase II (topo II), plays a
      major role in mitotic chromosome segregation after DNA replication. The classical
      topo II poisons act by stabilizing the enzyme in the so-called cleavable complex
      and result in DNA damage as well as END, while the true catalytic inhibitors,
      which are not cleavable-complex-stabilizers, do induce END without concomitant
      DNA and chromosome damage. Taking into account these observations on the
      induction of END by drugs that interfere with topo II, together with our recently
      obtained evidence that the nature of DNA plays an important role for chromosome
      segregation [Cortes, F., Pastor, N., Mateos, S., Dominguez, I., 2003. The nature
      of DNA plays a role in chromosome segregation: endoreduplication in halogen
      substituted chromosomes. DNA Repair 2, 719-726.], a straightforward model is
      proposed in which the different mechanisms leading to induced END are considered.

PMID- 15519360
TI  - Hypoglycemic and hypolipidemic effects and antioxidant activity of fruit extracts
      from Lycium barbarum.
AB  - The hypoglycemic and hypolipidemic effects of Lycium barbarum fruit water
      decoction, crude polysaccharide extracts (crude LBP), and purified polysaccharide
      fractions (LBP-X) in alloxan-induced diabetic or hyperlipidemic rabbits were
      investigated through designed sequential trials and by measuring blood glucose
      and serum lipid parameters. Total antioxidant capacity was also assessed using
      trolox equivalent antioxidant capacity (TEAC) and oxygen radical absorbance
      capacity (ORAC) assay. It was found that the three Lycium barbarum fruit
      extracts/fractions could significantly reduce blood glucose levels and serum
      total cholesterol (TC) and triglyceride (TG) concentrations and at same time
      markedly increase high density lipoprotein cholesterol (HDL-c) levels after 10
      days treatment in tested rabbits, indicating that there were substantial
      hypoglycemic and hypolipidemic effects. Hypoglycemic effect of LBP-X was more
      significant than those of water decoction and crude LBP, but its hypolipidemic
      effect seemed to be weaker. Total antioxidant capacity assay showed that all
      three Lycium barbarum extracts/fractions possessed antioxidant activity. However,
      water and methanolc fruit extracts and crude polysaccharide extracts exhibited
      stronger antioxidant activity than purified polysaccharide fractions because
      crude extracts were identified to be rich in antioxidants (e.g., carotenoids,
      riboflavin, ascorbic acid, thiamine, nicotinic acid). Lycium barbarum
      polysaccharides (glycocojugates), containing several monosaccharides and 17 amino
      acids, were major bioactive constituents of hypoglycemic effect. Both
      polysaccharides and vitamin antioxidants from Lycium barbarum fruits were
      possible active principles of hypolipidemic effect.

PMID- 15519361
TI  - Neuroprotective effects of ONO-1924H, an inhibitor of poly ADP-ribose polymerase
      (PARP), on cytotoxicity of PC12 cells and ischemic cerebral damage.
AB  - N-[3-(4-Oxo-3,4-dihydro-phthalazin-1-yl)phenyl]-4-(morpholin-4-yl) butanamide
      methanesulfonate monohydrate (ONO-1924H) is a novel inhibitor of poly ADP-ribose
      polymerase (PARP). In this study, we examined the effects of ONO-1924H on
      cytotoxicity induced by hydrogen peroxide in PC12 cells in vitro and cerebral
      damage and neurological deficits induced by middle cerebral artery (MCA) thrombus
      occlusion in vivo in rat. In the in vitro cytotoxicity assay, exposure to 0.5
      mmol/L hydrogen peroxide induced cell death in differentiated PC12 cells. ONO
      1924H, a PARP inhibitor (Ki=0.21 micromol/L), reduced cell death in a
      concentration-dependent manner that was correlated with inhibition of PARP
      activation. A 50% reduction in cell death (EC50) was achieved with 2.4 micromol/L
      ONO-1924H. In the MCA occlusion model, ONO-1924H was injected intravenously at
      doses of 3, 10 and 30 mg/kg/h for 3 h, and cerebral damage and neurological
      deficits were estimated 24 h after MCA occlusion. ONO-1924H treatment led to a
      significant decrease in cerebral damage in the 10 mg/kg/h-treated group (P <
      0.05) and the 30 mg/kg/h-treated group (P < 0.01). Further, ONO-1924H at doses of
      30 mg/kg/h significantly (P < 0.05) improved neurological deficits. These
      findings suggest that the novel PARP inhibitor, ONO-1924H, affords effective
      neuroprotection and is a useful therapeutic candidate for the treatment of
      ischemic stroke.

PMID- 15519362
TI  - Long-term induction of beta-CGRP mRNA in rat lungs by allergic inflammation.
AB  - Calcitonin gene-related peptide (CGRP) is one of the major neuropeptides released
      from sensory nerve endings and neuroendocrine cells of the lung. Two CGRP
      isoforms, alpha-and beta-CGRP, have been identified in rats and humans, but no
      studies have attempted to reveal direct evidence of differences in action or
      location of these isoforms in allergic inflammation (AI). We investigated mRNA
      expressions of alpha-and beta-CGRP in lungs, nodose ganglia (NG), and dorsal root
      ganglia (DRG) of an animal model for AI of the airways, utilizing a model created
      by sensitizing Brown Norway (BN) rats with ovalbumin (OVA). By semiquantitative
      RT-PCR analysis, long-lasting enhanced expression of the beta-CGRP mRNA was shown
      in the lungs of the AI rats (14.5-fold enhancement at 6 hr, 8.1-fold at 24 hr,
      and 3.7-fold at 120 hr after OVA-challenge compared to the level in the lungs of
      phosphate-buffered saline (PBS)-challenged control rats). In contrast, the mRNA
      expression of the alpha-CGRP in AI lungs showed only a transient increase after
      OVA-challenge (2.7-fold at 6 hr) followed by a lower level of expression (0.5
      fold at 48 hr and 0.6-fold at 120 hr). The mRNA expressions of both isoforms in
      NG, but not in DRG, were transiently up-regulated at 6 hr after antigen
      challenge. In situ RT-PCR in combination with immunohistochemical analysis
      revealed that beta-CGRP was expressed in neuroendocrine cells in clusters (termed
      neuroepithelial bodies [NEBs]) in AI lungs. These results indicate that the long
      term induction of beta-CGRP in NEBs may play an important role in pulmonary AI
      such as bronchial asthma.

PMID- 15519363
TI  - Possible involvement of enhanced intestinal microsomal triglyceride transfer
      protein (MTP) gene expression in acceleration of lipid absorption by a western
      type diet in apolipoprotein E knockout mice.
AB  - Evidence has been accumulating that triglyceride (TG)-rich lipoproteins are
      atherogenic. Microsomal TG transfer protein (MTP) is essential for the synthesis
      of both chylomicron in the intestine and very low density lipoprotein in the
      liver. To investigate whether a western-type diet, a so-called atherogenic diet,
      alters intestinal lipid absorption via change in intestinal MTP expression, the
      effects of two different diet regimes in apolipoprotein-E knockout (apoE KO) mice
      were examined. Male apoE KO mice aged 6 weeks were fed a western-type diet or a
      chow diet for 5 weeks. Then, measurement of plasma TG levels after oral fat
      loading and analysis of jejunal MTP gene expression were performed. Both the
      maximum level and the 0-8 h area under the curve (AUC) of the increase in TG
      levels in the western-type diet-fed mice were almost three times greater than
      those in the chow diet-fed mice. MTP gene expression, determined by reverse
      transcriptase-polymerase chain reaction (RT-PCR), was obviously enhanced in the
      western-type diet-fed mice compared to the chow diet-fed mice. These results
      suggest that the enhancement of intestinal MTP gene expression is involved in the
      accelerated lipid absorption in the western-type diet-fed mice.

PMID- 15519364
TI  - The inhibitory effect of a herbal formula comprising ginseng and carthamus
      tinctorius on breast cancer.
AB  - A compound (Zhu-xiang) from herbal extracts containing ginseng and carthamus
      tinctorius was used to treat the MDA-MB-231 breast cancer cell and normal human
      mammary gland cell lines. The inhibition of cell proliferation by Zhu-xiang,
      epirubicin, 5-fluorouracil and cyclophosphamide was determined by WST-1 assays.
      The apoptotic effect was studied by flow cytometry analysis of DNA strand breaks
      and ApopTag Peroxidase In Situ Apoptosis kit by the TUNEL assay. The
      proliferation index as well as cell cycle progression were also evaluated by flow
      cytometry using Ki-67 and propidium iodide respectively as markers. The Zhu-xiang
      showed significantly inhibition in cell proliferation and the inhibition was dose
      dependent. The inhibitory effect of Zhu-xiang was significantly greater than
      commonly used cytotoxic drugs. The inhibitory effect is a result of the induction
      of apoptosis, which is concentration- and time-dependent. DNA histograms indicate
      that the compound causes accumulation of cells mainly in the S phase. The
      viability of cells in breast solid tumours was measured by ATP bioluminescence
      assay to determine the drug-induced cytotoxicity of Zhu-xiang. The three
      different concentrations of Zhu-xiang all exhibited the ability to inhibit
      proliferation in solid tumour. Zhu-xiang could be a useful anti-cancer compound
      against breast cancer.

PMID- 15519365
TI  - The effects of magnesium sulfate on blood-brain barrier disruption caused by
      intracarotid injection of hyperosmolar mannitol in rats.
AB  - The study was performed to evaluate whether magnesium sulfate could alter the
      degree of disruption of the blood-brain barrier (BBB) caused by hyperosmotic
      mannitol. Wistar adult female rats were infused with 25% mannitol into the left
      internal carotid artery. Each animal received intraperitoneally a 300 mg/kg
      loading dose of magnesium sulfate, dissolved in 0.9% saline, followed by a
      further 100 mg/kg dose. In the other group, intracarotid infusion of magnesium
      sulfate was performed at a dose of 150 mg/kg 10 min before mannitol
      administration. Evans blue (EB) dye was used as a marker of BBB disruption. The
      measured serum glucose and magnesium levels increased after mannitol and/or
      magnesium administration when compared with their initial values before treatment
      (P < 0.01). Water content of the left hemisphere was significantly increased by
      hyperosmotic mannitol (P < 0.01). The increased water content in the mannitol
      perfused hemisphere was significantly decreased by magnesium treatment (P <
      0.05). The content of EB dye in the mannitol-perfused hemisphere markedly
      increased when compared with the right hemisphere of the same brain (P < 0.01).
      The EB dye content in the mannitol-perfused hemisphere following both
      intraperitoneal and intraarterial administration of magnesium decreased when
      compared with mannitol alone (P < 0.01). We conclude that although magnesium
      sulfate administration by both intracarotid arterial and intraperitoneal routes
      attenuates BBB disruption caused by hyperosmolar mannitol, particularly
      intraperitoneal route of magnesium sulfate administration may provide a useful
      strategy to limit the transient osmotic opening of the BBB.

PMID- 15519366
TI  - Antinociceptive and gastroprotective effects of inhaled and orally administered
      Lavandula hybrida Reverchon "Grosso" essential oil.
AB  - In this study the antinociceptive and the gastroprotective effects of orally
      administered or inhaled Lavandula hybrida Reverchon "Grosso" essential oil, and
      its principal constituents linalool and linalyl acetate were evaluated in
      rodents. Either when orally administered (100 mg/kg) or inhaled for 60 min
      lavender essential oil significantly reduced the acetic acid-writhing response in
      a naloxone-sensitive manner. In the hot plate test, analgesic activity observed
      after oil inhalation was inhibited by naloxone, atropine, mecamylamine
      pretreatment suggesting the involvement of opioidergic as well as cholinergic
      pathways. Regardless of the administration route and the experimental model used
      both linalool and linalyl acetate did not produce significant analgesic response.
      Oral or inhalatory treatment with analgesic doses of essential oil did not affect
      mice spontaneous locomotor activity. Concerning the gastric effects, lavender
      oil, linalool and linalyl acetate oral administration protected against acute
      ethanol-induced gastric ulcers but did not prevent indomethacin-induced lesions
      indicating no interference with arachidonic acid metabolic cascade. In
      conclusion, besides this gastroprotection, lavender oil reveals an interesting
      analgesic activity mainly relevant after inhalation, at doses devoid of sedative
      side effect, suggesting the interest for potential application of this oil in
      aromatherapy.

PMID- 15519367
TI  - Atypical properties of several classes of antipsychotic drugs on the basis of
      differential induction of Fos-like immunoreactivity in the rat brain.
AB  - Acute administration of typical and atypical antipsychotics has been reported to
      induce regionally distinct patterns of c-Fos expression in the rat forebrain.
      Furthermore, atypical index, the difference in the extent of increased Fos-like
      immunoreactivity (Fos-LI) in the nucleus accumbens (NAc) shell versus the
      dorsolateral striatum (DLSt), has been proposed to classify antipsychotics into
      typical or atypical antipsychotics. The present study was conducted to
      investigate the atypical properties of 24 antipsychotics that are used in Japan
      and blonanserin, a novel 5-HT2A and D2 receptor antagonist. We systematically
      examined the effects of the drugs on Fos-LI in the NAc and DLSt in the rat brain
      using immunohistochemistry and calculated the atypical index, comparing with
      those of haloperidol and clozapine. Floropipamide, oxypertine, nemonapride,
      pimozide and mosapramine, as well as clozapine, olanzapine, quetiapine and
      risperidone, showed high positive atypical index. Zotepine, perospirone,
      sulpiride, moperone, sultopride, thioridazine, carpipramine, clocapramine and
      blonanserin showed moderate ones. In contrast, fluphenazine, bromperidol,
      timiperone, spiperone, propericiazine, perphenazine, chlorpromazine and
      levomepromazine had negative atypical index like haloperidol. These results
      suggest that not only so-called atypical antipsychotics, but also several
      conventional drugs, possess atypical properties.

PMID- 15519368
TI  - Adsorption and cosorption of cadmium and glyphosate on two soils with different
      characteristics.
AB  - Glyphosate [N-(phosphonomethyl)glycine] (GPS; H3G) is a widely used pesticide
      throughout the world. It affects metal behaviors in soil-plant system due to its
      functional groups, which react with metal ions to form metal complexes.
      Adsorption and cosorption of cadmium and glyphosate on a Wushan soil (WS soil,
      Anthrosol) and a Zhuanhong soil (ZH soil, Udic Ferrisol) as affect by solution pH
      were studied by means of batch adsorption experiments. It indicated that the
      adsorption quantity of Cd or glyphosate was highly relevant to soil
      characteristics. The WS soil had higher adsorption capacity of Cd than the ZH
      soil, due to its high organic matter content and cation exchange capacity (CEC).
      In contrast, the adsorption quantity of glyphosate on the WS soil was less than
      that on the ZH soil, because the WS soil has lower iron and aluminum oxides
      content but higher pH than the ZH soil. The herbicide glyphosate affected Cd
      adsorption on the two soils when they coexisted in a same soil solution, which
      was attributed to a glyphosate-induced pH-decrease and the corresponding decline
      in negative surface charges of the soil. Beside that, glyphosate reacted with
      solution Cd to form the water-soluble complexes that had lower affinity to soil
      surface in comparison with Cd itself. On the other hand, the presence of Cd in
      the soil solution also affected the adsorption of glyphosate on the soils. The
      presence of Cd increased adsorption quantity of glyphosate on the WS and ZH
      soils, which was resulted from the decrease of equilibrium solution pH caused by
      Cd2+ exchange with H+ ions of soil surface. In addition to that, glyphosate
      adsorption possibly takes place on sites where Cd was previously adsorbed and
      acted as a bridge between the soil and glyphosate.

PMID- 15519369
TI  - Analysis of extinction in ultraviolet and visible spectra of water bodies of the
      Paraguay and Brazil wetlands.
AB  - The extinction spectra in ultraviolet and visible radiation were analyzed using
      filtered and unfiltered water samples obtained in 11 open water bodies in the
      Neembucu (Paraguay) and Pantanal (Brazil) wetlands. The role of dissolved and
      suspended matter in the total extinction was analyzed between 260 nm and 700 nm.
      The chromophoric dissolved organic matter (CDOM) was the major component in
      extinction of considered ultraviolet radiation (260-400 nm). The differences in
      CDOM concentrations explained the main pattern of extinction of the ultraviolet
      radiation in the samples. Nevertheless, differences between the studied water
      bodies were found also to depend on the rate of photodegradation and
      photobleaching. The methodology developed in the present study was to distinguish
      "humic optic waters" according to quantity and quality of dissolved and suspended
      matter present. In the "humic optic water", the penetration of 10% of incident UV
      radiation and the photoactive layer are estimated. The influence of particulate
      matter increases in the total extinction of the wavelengths higher than 400 nm.
      The integral of the extinction curve of suspended matter in the visible
      wavelengths (400-700 nm) was found to relate with the total suspended solids and
      chlorophyll concentrations.

PMID- 15519370
TI  - Investigating the affinities and persistence of VX nerve agent in environmental
      matrices.
AB  - Laboratory experiments were conducted to determine environmental variables that
      affect the affinities and persistence of the nerve agent O-ethyl S-(2
      diisopropylaminoethyl) methylphosphonothiolate (VX) at dilute concentrations in
      environmental matrices. Quantitative analyses of VX and its degradation products
      were performed using LC-MS. Batch hydrolysis experiments demonstrated an
      increasing hydrolysis rate as pH increased, as shown in previous studies, but
      also indicated that dissolved aqueous constituents can cause significant
      differences in the absolute hydrolysis rate. Adsorption isotherms from batch
      aqueous experiments revealed that VX has a high affinity for hydrophobic
      organics, a moderate affinity for montmorillonite clay, and a very low affinity
      for an iron-oxyhydroxide soil mineral, goethite. The adsorption on goethite was
      increased with the presence of dissolved organic matter in solution. VX degraded
      rapidly when dried onto goethite, when specific adsorption was forced. No
      enhanced degradation occurred with goethite in small amounts of water. These
      results suggest that aqueous conditions have important controls on VX adsorption
      and degradation in the environment and a more mechanistic understanding of these
      controls is needed in order to enable accurate predictions of its long-term fate
      and persistence.

PMID- 15519371
TI  - Determination of volatile organohalogen compounds in urban precipitation in
      Tricity area (Gdansk, Gdynia, Sopot).
AB  - Chlorinated and brominated derivatives of methane and ethene were determined in
      samples of atmospheric precipitation collected between November 2000 and May 2001
      at four sites in two cities, Gdansk and Sopot, located on the Gulf of Gdansk
      (Baltic Sea, Poland). The analytes were determined by direct aqueous injection of
      the samples to the capillary column using ECD detection (DAI-GC-ECD). Chloroform
      and carbon tetrachloride were detected the most often at all sites. The highest
      concentrations of the analytes were recorded at the intersection of two major
      streets (no. 3), next to a major route leading to two subdivisions (no. 2) and at
      Narutowicza Street (no. 1). In general, analyte concentration levels were lower
      during the spring months. During precipitation, concentrations of the analytes
      were higher in samples collected at the beginning of the event due to scavenging
      of the volatile compounds from the atmosphere. After a period of 75 min from the
      beginning of the precipitation event, analyte concentrations were lower by 10
      80%, depending on the initial concentration and nature of the analyte.

PMID- 15519372
TI  - The anthropogenic contribution to the organic load of the Lippe River (Germany).
      Part I: Qualitative characterisation of low-molecular weight organic compounds.
AB  - GC/MS-screening analyses of water samples from the Lippe River, Germany, revealed
      the presence of a wide spectrum of low-molecular weight organic compounds ranging
      from non-polar constituents like aliphatic hydrocarbons to polar constituents
      like n-carboxylic acids and phenols. Most of the identified compounds could be
      attributed to anthropogenic input and are used as plasticizers, flame retardants,
      pharmaceutical drugs or fragrances. Some of them had rarely been noticed as
      organic pollutants of aquatic environments before. These are, among others, 9
      methylacridine, the plasticizer 2,2,4-trimethyl-1,3-pentandioldiisobutyrate
      (TXIB), the surfactant 2,4,7,9-tetramethyl-5-decyne-4,7-diol (TMDD),
      triphenylphosphinoxide and the flame retardant tris(chloropropyl)phosphate. On
      the other hand, most of the identified trialkyl phosphates, pharmaceutical drugs
      and synthetic fragrances have been reported in surface waters by several authors
      so far. Input pathways of the detected compounds were traced back by sampling
      various input sources of organic matter such as discharges of wastewater and
      Lippe River tributaries. Several contaminants were ubiquitous in Lippe River
      water and also occurred in sewage effluent from a municipal sewage treatment
      plant and in samples from the tributaries. This observation suggests that they
      are typical sewage derived contaminants and have the potential to be used as
      anthropogenic molecular markers.

PMID- 15519373
TI  - The anthropogenic contribution to the organic load of the Lippe River (Germany).
      Part II: Quantification of specific organic contaminants.
AB  - The major goal of this study was to investigate the organic pollution of a river
      on a quantitative basis. To this end, 14 anthropogenic contaminants which were
      identified in Lippe River water samples as reported in part I (Dsikowitzky et
      al., submitted parallel to this manuscript) were surveyed. Dissolved organic
      loads of the specific compounds were calculated on the basis of their
      concentrations in water and river runoff on the day of sampling. The organic
      loads of each compound were compiled along the longitudinal section of the river
      in order to generate individual spatial pollution profiles. It was observed that
      distribution of organic loads along the river showed distinctive patterns,
      depending upon the input situation and physico-chemical properties of the
      compound. The compounds were classified into three types of which Type 1, due to
      their stability in the aqueous phase, are of special interest for potential
      application as anthropogenic markers.

PMID- 15519374
TI  - pH dependence of ferrous sorption onto two smectite clays.
AB  - This work examines the abilities of two smectite minerals (SWa-1 and Wyoming
      montmorillonite) to adsorb ferrous iron at concentrations from 0.037 mM (2 ppm)
      to 2.5 mM (240 ppm) over a range of pHs from 4.0 to 8.0. Both sorption isotherm
      and sorption edge data are presented. Ferrous sorption (Fe(aq)2+ = 0.1 mM) to
      both SWa-1 and Wyoming montmorillonite over the pH range 4.0-6.75 is relatively
      constant at approximately 1000 l kg(-1) for both minerals. Sorption in this pH
      range is attributed to the cation exchange capacity of the clay along the basal
      surfaces. At pH values above 6.75 the amount of ferrous iron sorbed increases
      dramatically. At pH 8, sorption (Fe(aq)+ = 0.1 mM) reaches 6600 l kg(-1) and 8000
      l kg(-1) for Swa-1 and Wyoming montmorillonite respectively. This is attributed
      to the specific interaction between ferrous ions and surface sites along mineral
      edges. The overriding geochemical implication is that in reduced sediments
      containing more than a few percent clay, the pool of sorbed ferrous iron is vast.
      This pool of reduced iron is both redox labile and bio-available and is not
      readily indicated by simple measurement of dissolved Fe2+.

PMID- 15519375
TI  - Mineralisation of Monuron photoinduced by Fe(III) in aqueous solution.
AB  - The degradation of Monuron (3-(4-chlorophenyl)-1,1-dimethylurea) photoinduced by
      Fe(III) in aqueous solution has been investigated. The rate of degradation
      depends on the concentration of Fe(OH)2+, the most photoreactive species in terms
      of *OH radical formation. These *OH radicals are able to degrade Monuron until
      total mineralisation. The primordial role of the speciation of Fe(III)-hydroxy
      complex in aqueous solution, for the efficiency of the elimination of pollutant,
      was shown and explained in detail. The formation of Fe(II) in the irradiated
      solution was monitored and correlated with the total organic carbon evolution.
      Degradation photoproducts were identified and a mechanism of degradation is
      proposed.

PMID- 15519376
TI  - Formation of PCDD/Fs and PCBs in the process of production of 1,4
      dichlorobenzene.
AB  - The occurrence and distribution of polychlorinated dibenzo-p-dioxins (PCDDs),
      polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs) in a
      typical process of production of 1,4-dichlorobenzene (p-DCB) were investigated
      systematically in this study. P5CDFs and H6CDFs were the main congeners of
      PCDD/Fs, while only low levels of other PCDD/Fs were detected in the samples. The
      concentrations of PCBs were up to 4614 ng/g in the semi-manufactured products,
      and 1797 ng/g in the product p-DCB. It was also found that high chlorinated PCB
      congeners increased with the further chlorination. The levels of PCDD/Fs
      decreased obviously in the purification process, while PCBs could not be removed
      effectively. Polychlorophenols and other important dioxin precursors (1,4
      dichloro-2-phenoxybenzene and 2-phenyl-2',5,5'-trichlorophenol) were also
      analyzed. Polychlorophenols which ortho- and para-positions of the hydroxyl were
      substituted by chlorine were the main congeners. In addition, a possible pathway
      of the formation of PCDD/Fs and PCBs in the production of p-DCB was presented.
      The results of this article suggest that re-estimation on the risk of using p-DCB
      products, especially the products for daily use such as mothballs, is expected.

PMID- 15519377
TI  - Cadmium adsorption and desorption behaviour on goethite at low equilibrium
      concentrations: effects of pH and index cations.
AB  - The transport and bioavailability of cadmium is governed mainly by its adsorption
      desorption reactions with minerals such as goethite--a common iron oxide mineral
      in variable charged and highly weathered tropical soils. Soil factors such as pH,
      temperature, solution Cd concentration, ionic strength and ageing affect Cd
      adsorption on goethite. The desorption behaviour of Cd from goethite at low
      concentrations is not fully understood. This study investigates the adsorption
      desorption of Cd at low Cd concentrations (Cd adsorbed on goethite from 20 to 300
      microM Cd solutions) in Na and Ca nitrate solutions of 0.03 M nominal ionic
      strengths. Synthetic goethite prepared by ageing a ferric hydroxide gel at high
      pH and room temperature was used for Cd adsorption and desorption studies. For
      desorption experiment 10 successive desorptions were made for the whole range of
      initial Cd concentrations (20-300 microM) in the presence of 0.01 M Ca(NO3)2 or
      0.03 M NaNO3 solutions. Cadmium adsorption was found to be higher in Na+ than
      Ca2+ probably due to the competition of Ca2+ ions with Cd2+ ions for adsorption
      sites on the surfaces of goethite. The effect of index cation on Cd adsorption
      diminished with increase in pH from 5.0 to 6.0. Cadmium desorption decreased with
      increase in pH from 5.0 to 6.0 in both Na and Ca systems. After 10 successive
      desorptions with 0.03 M NaNO3 at the lowest initially adsorbed Cd approximately
      45%, 20% and 7% of the adsorbed Cd was desorbed at pH 5.0, 5.5 and 6.0,
      respectively. The corresponding desorptions in the presence of 0.01 M Ca(NO3)2
      were 49%, 22% and 8%, respectively. The Freundlich parameter, k, based on each
      progressive step of desorption at different adsorbed concentration increased with
      increasing desorption step, which may indicates that a fraction of Cd was
      resistant to desorption. Low Cd desorbability from goethite may be due to its
      specific adsorption and/or possibly as a result of Cd entrapment in the cracks or
      defects in goethite structure.

PMID- 15519378
TI  - Mass spectrometry up to 1 million mass units for the simultaneous detection of
      primary soot and of soot precursors (nanoparticles) in flames.
AB  - A hybrid setup consisting of low pressure burner, flow reactor and photo
      ionization mass spectrometer was used for the simultaneous detection of primary
      soot and of flame generated nanoparticles precursing soot. The studied flames
      were low pressure (120-180 mbar) C2H4/O2 flames surrounded by an N2 shield. The
      flow reactor was not used in this study. Through variation of the burner
      conditions (stoichiometry, sampling height) it could be shown that nanoparticles
      and soot are entirely independent species. The former, in particular, are found
      very early in the flame and their concentration profiles do not vary very much
      throughout the flame. This renders the possibility that nanoparticles are emitted
      together with soot and consequently may constitute an additional environmental
      hazard. Photo-ionization mass spectrometry is well suited for the detection of
      these particles.

PMID- 15519379
TI  - Organohalogenated compounds in pine needles from Beijing city, China.
AB  - Pine needles collected from 22 sites of six areas in Beijing city, China, were
      analyzed by instrumental neutron activation analysis (INAA) combined with organic
      extraction for extractable organohalogens (EOX) and extractable persistent
      organohalogens (EPOX). The concentrations of EOX (EOX = ECl + EOBr + EOI) were in
      the order of EOCl >> EOBr > EOI. About 1.6-34% of EOCl remained as extractable
      persistent organochlorine (EPOCl) after treatment with concentrated sulfuric
      acid, which suggested that major fractions of EOCl in pine needles were an acid
      liable or acid-soluble fraction. The fact that pine needle contained higher EOCl
      contents in chemical industrial and traffic hub areas indicated that chemical
      industries and exhaust emission from vehicle were the main sources of
      organochlorines in the Beijing's air. The relative proportions of the known
      organochlorines (such as HCHs, DDTs, chlordanes, HCB and PCBs) to total EOCl and
      EPOCl were 0.32-0.76% and 2.5-11.4%, respectively, which implied that a major
      portion of the EOCl and EPOCl measured in pine needles was unknown. The
      organochlorinated pesticides (OCPs) and PCBs concentrations in six areas were as
      follows: sigma HCH (sigma HCH = alpha- + beta- + gamma- + delta-HCH), 11.7-20.8
      ng/g; sigma DDT (p,p'-DDT + p,p'-DDE + p,p'-DDD), 12.5-113.3 ng/g;
      hexachlorobenzene (HCB), 1.1-5.3 ng/g; sigma chlordane (cis-chlordane + trans
      chlordane + heptachlor), 1.7-9.5 ng/g, sigma PCB, 41.8-270.5 ng/g, on dry weight
      basis. The samples from chemical industrial area and residential area nearby
      chemical industries contained the highest concentrations of sigma DDT, HCB, sigma
      chlordane and sigma PCB, while the contamination levels of most OCPs and PCBs in
      iron-steel industrial area were the lowest. The ratios of alpha/gamma-HCH (ranged
      from 0.9-1.5) and p,p'-DDT/DDTs (ranged from 72.1% to 91.0%) revealed the
      presence of the recent use of lindane and DDTs or impure dicofol in Beijing.

PMID- 15519380
TI  - Interspecific and geographical variations of trace element concentrations in
      Pectinidae from European waters.
AB  - Cd, Cu and Zn were analysed in the organs and tissues of the three scallop
      species from the Bay of Biscay, the variegated Chlamys varia L., the queen
      scallop Aequipecten opercularis L. and the common scallop Pecten maximus L. for
      interspecific comparisons. In P. maximus the greatest concentrations of Cd and Cu
      were found in the digestive gland, whereas the two other species showed similar
      levels of Cd between digestive gland and kidneys and higher renal Cu
      concentrations. However, the digestive gland of all Pectinidae species contained
      from 75% to 93% and 52% to 74% of the total body burdens of Cd and Cu,
      respectively. Whatever the species, kidneys displayed the highest Zn
      concentrations, which therefore contained from 53% to 97% of the total body
      burden of this metal. Also using reported results, ratios between the
      concentrations in the digestive gland and that in the kidneys discriminated two
      groups of Pectinidae: (1) the Pecten group (P. maximus, P. jacobeus and
      Adamussium colbecki) with a Cd ratio > or = 4, a Cu ratio > or = 1 and a Zn ratio
      > 20x10(-3); (2) the Chlamys group with a Cd ratio < or = 1, a Cu ratio < or = 1
      and a Zn ratio < or = 6x10(-3). However, no differences in the detoxification
      processes in the digestive gland were found between groups in this study. 72-80%
      of the total Cd was found to be soluble, probably bound to metalloproteins such
      as metallothioneins, while Cu and Zn were mainly found associated to the
      insoluble fraction of the digestive gland cells whatever the species. Queen
      scallops from the Faroe Islands were also considered to examine variations of the
      metal concentrations due to the geographical origin. In this northern area, queen
      scallops displayed Cd concentrations 2, 4 and 6 times higher in kidneys, muscle
      and digestive gland, respectively, compared to those from the Bay of Biscay.
      Consequently, the Cd concentrations in the whole soft parts of the queen scallops
      were more than 6 times higher in the Faroe Islands than in the Bay of Biscay. In
      contrast to Cd, both Cu and Zn concentrations in the whole soft parts were 2
      times lower in the Faroe Islands, suggesting lower bioavailability of these
      essential elements.

PMID- 15519381
TI  - Characterization of hydrocarbons, halocarbons and carbonyls in the atmosphere of
      Hong Kong.
AB  - Ambient air quality measurements of 156 species including 39 alkanes, 32 alkenes,
      2 alkynes, 24 aromatic hydrocarbons, 43 halocarbons and 16 carbonyls, were
      carried out for 120 air samples collected at two sampling stations (CW and TW) in
      2001 throughout Hong Kong. Spatial variations of volatile organic compounds
      (VOCs) in the atmosphere were investigated. Levels of most alkanes and alkenes at
      TW site were higher than that at the CW site, while the BTEX concentrations at
      the two sites were close. The BTEX ratios at CW and TW were 1.6:10.1:1.0:1.6 and
      2.1:10.8:1.0:2.0, respectively. For major halogenated hydrocarbons, the mean
      concentrations of chloromethane, CFCs 12 and 22 did not show spatial variations
      at the two sites. However, site-specific differences were observed for
      trichloroethene and tetrachloroethene. Furthermore, there were no significant
      differences for carbonyls such as formaldehyde, acetaldehyde and acetone between
      the two sites. The levels of selected hydrocarbons in winter were 1-5 times that
      in summer. There were no common seasonal trends for carbonyls in Hong Kong. The
      ambient level of formaldehyde, the most abundant carbonyl, was higher in summer.
      However, levels of acetaldehyde, acetone and benzaldehyde in winter were 1.6-3.8
      times that in summer. The levels of CFCs 11 and 12, and chloromethane in summer
      were higher than that in winter. Strong correlation of most hydrocarbons with
      propene and n-butane suggested that the primary contributors of hydrocarbons were
      vehicular emissions in Hong Kong. In addition, gasoline evaporation, use of
      solvents, leakage of liquefied petroleum gas (LPG), natural gas leakage and other
      industrial emissions, and even biogenic emissions affected the ambient levels of
      hydrocarbons. The sources of halocarbons were mainly materials used in industrial
      processes and as solvents. Correlation analysis suggested that photochemical
      reactions made significant contributions to the ambient levels of carbonyls in
      summer whereas in winter motor vehicle emissions would be the major sources of
      the carbonyls. The photochemical reactivity of selected VOCs was estimated in
      this study. The largest contributors to ozone formation were formaldehyde,
      toluene, propene, m,p-xylene, acetaldehyde, 1-butene/i-butene, isoprene and n
      butane, suggesting that motor vehicles, gasoline evaporation, use of solvents,
      leakage of LPG, photochemical processes and biogenic emission are sources in the
      production of ozone. On the other hand, VOCs from vehicles and gasoline
      evaporation were predominant with respect to reactions with OH radical.

PMID- 15519382
TI  - Vapour pressures, aqueous solubilities, Henry's Law constants, and octanol/water
      partition coefficients of a series of mixed halogenated dimethyl bipyrroles.
AB  - Basic physical-chemical properties of five bromine and chlorine containing mixed
      halogenated dimethyl bipyrroles (HDBPs) were determined using established
      methods. Subcooled liquid vapour pressures (P(o)(L,25)), aqueous solubilities
      (S(w,25)), and octanol/water partition coefficients (K(ow)) were determined using
      the gas chromatography-retention time, generator column, and slow-stirring
      methods, respectively. Henry's Law constants (H25) were estimated using
      experimentally-derived P(o)(L) and S(w,25) data. Values of all four properties
      were generally similar to those reported for other polyhalogenated aromatic
      compounds [P(o)(L,25) = (7.55-191) x 10(-6) Pa; S(w,25) = (1.0-1.9) x 10(-5) g/l;
      log K(ow) = 6.4-6.7; H25 = 0.0020-0.14 Pa m3/mol]. The effect of replacing a
      chlorine with a bromine atom significantly decreased P(o)(L,25) (log P(o)(L,25) =
      -0.4197 (# bromine atoms) - 2.643, p<0.01) and H25 (log H25 = -0.508 (# bromine
      atoms) + 0.394, p<0.02). There were no significant effects of bromine/chlorine
      substitution on S(w,25) or K(ow). A simple Level I equilibrium partitioning model
      predicted the environmental behaviour of HDBPs to be similar to a tetrabrominated
      diphenyl ether. Only slight differences in behaviour amongst HDBP congeners were
      predicted since substitution of a bromine for a chlorine (Cl/Br substitution)
      atom had less effect than H/Cl or H/Br substitution on P(o)(L,25), S(w,25), H25,
      and K(ow).

PMID- 15519383
TI  - EPR characterization of the catalytic activity of clays for PCE removal by gamma
      radiation induced by acid and thermal treatments.
AB  - Clays from tidal flat sediments showed efficient catalytic activity in the
      decomposition of PCE by gamma-radiation. The highest PCE removal of 98.6% was
      obtained with clays heated to 700 degrees C after acid treatment. The improved
      catalytic activity was identified by electron paramagnetic resonance (EPR)
      spectroscopy. The EPR spectra of clays were significantly changed by the acid and
      thermal treatments. The intensity of a narrow signal at g=2 (signal III) was
      decreased with increasing thermal treatment temperature and this increased the
      PCE removal efficiency. The acid treatment completely removed a broad signal at
      g=2 (signal II), decreased the intensity of signal III, and improved the gamma
      radiation treatment of PCE.

PMID- 15519384
TI  - Current multi-element distribution in forest epigeic moss in the Czech Republic-
      a survey of the Czech national biomonitoring programme 2000.
AB  - The content of 35 elements was determined in moss samples collected at 250 sites
      in the Czech Republic (CZ) in 2000. Four main areas of increased element contents
      in moss were revealed in the CZ (southern Moravia, Czech part of the former Black
      Triangle I territory, industrial northeastern Moravia, and the surroundings of a
      smelting town in southwestern Bohemia). The bioindicated high levels of Al, Ce,
      Co, Ga, La, Li, Pr, S, Th, U, V and Y atmospheric deposition loads in southern
      Moravia have never been reported in any paper before. Correlations were found in
      element content in moss vs. altitude, precipitation sums and bedrock types of the
      moss sampling plots. The current variability of element content in the CZ moss
      samples can be explained by the operation of not more than six factors.

PMID- 15519385
TI  - Photodegradation of organic pollutants on the spruce needle wax surface under
      laboratory conditions.
AB  - The photochemistry of selected organic compounds, including common pollutants, on
      the paraffin (as a model matrix) and spruce wax surfaces was studied under
      laboratory conditions. Two model transformations were evaluated: (1)
      intramolecular rearrangements of valerophenone and 2-nitrobenzaldehyde, and (2)
      hydrogen abstraction between an excited benzophenone and the hydrocarbon
      paraffin/wax chains. The steric or polar influence of the solid matrix on
      conformational and translational motion, its optical properties, hydrogen
      abstraction probabilities, and consequences of the guest-molecule segregation are
      discussed in this work. Furthermore, the photochemical reactivity of some common
      anthropogenic pollutants, such as chlorinated biphenyls (4-chlorobiphenyl, 2,4
      dichlorobiphenyl, and 4,4'-dichlorobiphenyl), 4-chlorophenol, and DDT, was
      evaluated. The surface of spruce wax is presented as probable reaction medium for
      photochemical transformations. Although the matrix presents certain restrictions
      for bimolecular reactions, common photodegradations should be generally feasible
      in nature. In addition, paraffin was found to be a suitable model matrix for the
      studies of possible photochemical transformations that can occur on natural plant
      surfaces.

PMID- 15519386
TI  - Impact of FEBRA (fermented brown rice with Aspergillus oryzae) intake and
      concentrations of PCDDs, PCDFs and PCBs in blood of humans from Japan.
AB  - Impact of FEBRA (fermented brown rice with Aspergillus oryzae, a rich dietary
      fiber) intake on the concentrations of polychlorinated-biphenyls (PCBs), -dioxin
      like polychlorinated biphenyls (DLPCBs), -dibenzo-p-dioxins (PCDDs), and 
      dibenzofurans (PCDFs) in blood of nine married Japanese were studied for 2 years.
      Concentrations of total PCBs (average+/-standard deviation) were greater
      326,000+/-263,000 and 207,000+/-89,000 in FEBRA-intake and non-FEBRA-intake
      groups, respectively, on pg/g lipid (from now onwards data expressed on pg/g
      lipid). DLPCBs were second major contaminants 94,000+/-77,000 and 60,000+/
      28,000, orderly in FEBRA-intake and non-FEBRA-intake groups. The concentrations
      of PCDD/DFs were several orders of magnitude lower than those of PCBs, whereas
      PCDDs were greater (433+/-233 and 512+/-511, in FEBRA-intake and non-FEBRA-intake
      groups, respectively) than PCDFs (56+/-50 and 43+/-35). Calculated toxic
      equivalency (TEQ) concentrations were 34+/-24 and 23+/-10 in FEBRA-intake and non
      FEBRA-intake groups, respectively. In order to corroborate the impact of FEBRA,
      the changes of PCDD/DFs and PCB concentrations for 0.5-year, 1-year, 1.5-year,
      and 2-year samples were estimated from average concentration of 1-day before
      study commences and 1-week study samples. The results explicit FEBRA-intake group
      eliminated 7%, 33%, 45%, 36%, and 26% and non-FEBRA-intake group eliminated 8%,
      28%, 36%, 31%, and 20% of DLPCBs, PCDDs, PCDFs, PCDD/DF TEQ and total TEQ,
      respectively. This study is the first of its kind showing the possible
      elimination of PCDDs, PCDFs and their TEQ in humans from Japan after the
      consumption of FEBRA.

PMID- 15519387
TI  - A modelling assessment of the atmospheric fate of volatile methyl siloxanes and
      their reaction products.
AB  - Volatile methyl siloxanes break down in the atmosphere by reacting with OH
      radicals to form OH-substituted silanols. As the silanols become increasingly OH
      substituted they are increasingly likely to be removed from the atmosphere by wet
      and dry deposition. A simple equilibrium partitioning model was constructed to
      explore the relative rates of removal by different mechanisms (reaction vs.
      deposition) for siloxanes and their resultant silanols. A mass balance is
      calculated for the parent siloxane molecule and for each silanol, characterised
      by the number of OH substitutions. The model includes the effect of incomplete
      equilibrium between the vapour, adsorbed and dissolved phases of silanols in the
      atmosphere using a non-equilibrium factor (epsilon) expressing relative departure
      from equilibrium. Model results show: (1) maximum vapour-phase concentrations for
      non-substituted siloxanes and single-OH-substituted silanols; (2) maximum
      dissolved-phase and adsorbed-phase concentrations for two-OH-substituted
      silanols; (3) >99% of the original material will be removed in wet deposition and
      <1% in dry deposition as silanols. For increasing OH-substitutions, the
      decreasing concentration of precursor molecules (as a consequence of combined
      removal processes) means that concentrations are negligible, in all phases,
      beyond three or four substitutions. Predictions were relatively insensitive to
      assumed departures from phase equilibrium. Predictions of silanol hydrolysis in
      liquid water droplets suggest that the mix of diol chain lengths in precipitation
      may not be in thermodynamic equilibrium and will depend on atmospheric residence
      time and pH.

PMID- 15519388
TI  - Study on the possibility of hydrogen peroxide pretreatment and plant system to
      remediate soil pollution.
AB  - Hydrogen peroxide was widely selected as the chemical oxidant in chemical
      remediation or as the donor of oxygen in in situ aerobic bioremediation of
      organic pollutants. In this paper, hydrogen peroxide pretreatment and plant
      system was done to examine its possibility to remediate the heavy metal
      contaminated soil or heavy metal-organic combined contaminated soil. Heavy metal
      contaminated soil was collected from the heavily industrialized area, in Fuyang
      county, Zhejiang province, China. And heavy metal-organic combined contaminated
      soil was prepared from the same contaminated soil by spiking 100 microg g(-1) 2,4
      dichlorophenol (2,4-DCP). Results showed that H2O2 could improve the dissipation
      of 2,4-DCP and enhance the availability of Cu and Zn in soil. The greatly
      increased DOC (dissolved organic carbon) in the oxidation process was probably
      the main reason for the greatly increased water soluble Cu in higher pH
      condition. Water soluble Zn, however, easily rebound to soil components with the
      time being and had no positive relation with dissolved organic carbon. Planting
      with ryegrass influenced the behavior of pollutants in soil. It was observed that
      the dissipation of 2,4-DCP could be enhanced by the presence of plant roots and
      the availability of Cu and Zn in the planted soil was changed due to the
      mobilization and rebound mechanisms in the rhizosphere. Co-contamination of 2,4
      DCP caused the greater availability of Cu and Zn in H2O2 pretreatment. But with
      the ryegrass planting, it was easier to rebound to the less available phase in
      the rhizosphere. Both Cu and Zn concentration in shoots increased with the H2O2
      treatment. Therefore our results suggested that H2O2 pretreatment was probably a
      promising way for promoting the dissipation of persistent organic pollutants and
      enhancing the solubility of Cu and Zn in soil. A combination of H2O2 pretreatment
      and suitable plant might be an efficient alternative for remedying heavy metal or
      heavy metal-organic contaminated soil.

PMID- 15519389
TI  - Determination of quantum yields for the photolysis of Fe(III)-hydroxo complexes
      in aqueous solution using a novel kinetic method.
AB  - The determination of quantum yields for the photolysis of Fe(III)-hydroxo
      complexes is important for the quantitative investigation of hydroxyl radical
      (*OH) production, not only in a natural water body, but also in the photo-Fenton
      process. A novel kinetic method, using a *OH probe compound, was established for
      the determination of the quantum yields in this study. The method was based on
      measuring the pseudo-first-order rate constant of the photodecomposition of
      dimethylsulfoxide (DMSO) in which DMSO and its primary products scavenged the *OH
      at an identical rate. The preliminary experiments for the photodecomposition
      kinetics supported the suitability of DMSOs as a probe compound for determining
      quantum yields. The individual quantum yields for the photolysis of the monomeric
      Fe(III) complexes, in the wavelength range 240-380 nm, were determined by the
      photodecomposition kinetics of the hydroxyl radical (*OH) probe compound (DMSO).
      The determined values of the individual quantum yields were 0.046+/-0.00052 for
      Fe3+ (H2O)6 (hexaaquo ion) and 0.69+/-0.025 for Fe(OH)2+ (H2O)5 (hydroxypentaaquo
      ion) at 254 nm, and showed decreasing values with increasing wavelength, in the
      ranges of 240-380 nm. The quantum yields between 240 and 280 nm were newly
      reported in this study, and the values obtained between 280 and 380 nm were in
      good agreement with the literature values.

PMID- 15519390
TI  - Effect of chemical amendments on the concentration of cadmium and lead in long
      term contaminated soils.
AB  - The availability of metal in contaminated soil can be reduced by the addition of
      soil amendments. The objectives of this study are to study the effects of
      applying different soil amendments on the concentration of Cd and Pb in soil
      solution, DTPA or EDTA extractable Cd and Pb, and the uptake of Cd and Pb by
      wheat (Triticum vulgare) when growing in long-term Cd and Pb-contaminated soils,
      more than 20 years. The soil amendments, including check, compost, zinc oxide,
      calcium carbonate, calcium carbonate mixed with zinc oxide, and calcium carbonate
      mixed with compost, were conducted in a four replicates pot cultural study. The
      amended soils were incubated for six months under 60% of water holding capacity.
      Following incubation, wheat was grown for four months in greenhouse. Analyses of
      Cd concentration demonstrated a significant decrease in soil solution
      concentration and DTPA or EDTA extractable in soils amended with calcium
      carbonate or calcium carbonate mixed with ZnO (or compost) (p<0.01). These
      amendments can significantly reduce the Cd concentration in the grain, leaf and
      stem, or reduce the total Cd uptake in all parts of wheat species grown in highly
      contaminated soil amended with calcium carbonate or calcium carbonate mixed with
      ZnO (or compost) (p<0.01). The concentration of Cd in soil solution and extracted
      with DTPA or EDTA can predict the Cd concentration in wheat, especially for soil
      solution.

PMID- 15519391
TI  - Speciation of chromium in 12 agricultural soils from Turkey.
AB  - The objective of the study was to speciate and to evaluate various soil Cr
      species in relation to soil properties. Surface soil samples were taken from
      outskirts of the Cr factory and applied a sequential extraction procedure.
      Extracts analyzed in atomic absorption spectrophotometry (AAS). Chromium was
      partitioned into exchangeable Cr, Cr bound to carbonate, Fe-Mn oxide, and organic
      matter, and residual Cr. The most common form of chromium was in the residual
      form, followed by the organic form. Very low concentrations of Cr were found in
      the exchangeable and carbonate forms. Mean values of the extractable forms of Cr,
      expressed in percentages of total soil contents were: 0.94% exchangeable, 0.80%
      carbonates, 2.13% oxides, 7.08% organics and 89.81% residual. Multiple regression
      analysis of analytical data revealed that soil pH, contents of organic matter and
      calcium carbonate were the most important factor controlling the distribution of
      Cr forms determined.

PMID- 15519392
TI  - Determination of antibiotic substances in hospital sewage water using solid phase
      extraction and liquid chromatography/mass spectrometry and group analogue
      internal standards.
AB  - A method for determination of antibiotics in hospital sewage water has been
      developed and validated. Analogue internal standards for fluoroquinolones,
      sulfonamides, trimethoprim, beta-lactams (penicillins and cephalosporins),
      nitroimidazoles and tetracyclines were successfully used for calibration and
      shown to generally improve precision compared to external calibration. Matrix
      components caused ion suppression/enhancement effects during the MS detection for
      all analytes studied. Two effects were observed: general suppression and short
      term variations in the MS response. In the hospital sewage water large temporal
      variations in the analyte concentration were observed during the course of the
      sampling period (seven grab samples in 13 h). Analyte concentrations varied
      within the following ranges (in microg l(-1)): ciprofloxacin, 3.6-101.0;
      metronidazole, 0.1-90.2; sulfamethoxazole, 0.4-12.8; ofloxacin, 0.2-7.6;
      trimethoprim, 0.6-7.6; and doxycycline, 0.6-6.7.

PMID- 15519393
TI  - Influence of some additives to aluminium species distribution in aluminium
      coagulants.
AB  - Aluminium ions hydrolyse and polymerise into different species in water. Main
      aluminium species in aluminium coagulant solutions are monomeric Al species (Al1)
      and polymeric Al species Al13O4(OH)24(7+) (Al13). The aluminium species
      distribution in coagulant solutions can be influenced by many parameters. This
      paper studies influences of concentrations of total aluminium species (Al(t)) and
      other species--OH-, polysilicic acid and ferric species, which were added in
      aluminium coagulant solutions, on the aluminium species distribution through 27Al
      nuclear magnetic resonance (NMR) analysis. Results show that only Al1 and no Al13
      exist in coagulant solutions at higher Al(t) concentrations (over 1 mol l(-1)),
      while both species exist at lower Al(t) concentrations (0.1 mol l(-1)). The
      increase of OH/Al value (molar ratio) increases the concentration of Al13 in
      coagulant solutions, while the addition of polysilicic acid and ferric species
      decreases the concentration of Al13.

PMID- 15519394
TI  - An overview of OSPAR priority compounds and selection of a representative
      training set.
AB  - The aim of our study was to chemically characterize a set of priority substances
      in order to systematically select a representative set of heterogeneous
      substances for experimental studies of their persistence, bioaccumulation and
      toxicity (PBT). By including structurally diverse compounds in a PBT-screening
      protocol, structure-based knowledge would be achieved as a basis for more
      detailed studies of specific compounds from certain regions of the chemical
      domain. Initially compounds on the Draft Preliminary List of Substances of
      Possible Concern presented by the Oslo & Paris Commission (OSPAR) were subjected
      to broad chemical characterization using Principal Component Analysis (PCA).
      Molecular weight and seven physico-chemical descriptors collected from the
      literature, five calculated properties and 25 constitutional descriptors were
      used in this characterization. The OSPAR list represents a broad spectrum of
      substances, and thus provides a good basis for selecting heterogeneous
      substances. D-optimal design was applied to the first four principal components
      derived in the PCA. In total, 19 structurally diverse substances were chosen as
      representatives of the chemical domain including 353 substances.

PMID- 15519395
TI  - Cosolvent effect on the catalytic reductive dechlorination of PCE.
AB  - Reductive dechlorination of chlorinated organic contaminants is an effective
      approach to treat this widespread group of environmentally hazardous substances.
      Metalloporphyrins can be used to catalyze reduction reactions by shuttling
      electrons from a reducing agent (electron donor) to chlorinated organic
      contaminants, thus rendering them to non-chlorinated acetylene, ethylene or
      ethane as major products. Iron, nickel and vanadium oxide tetraphenyl porphyrins
      (TPPs) were used as models of non-soluble metalloporphyrins that are common in
      subsurface environments, and hence may inflect on the ability to use natural
      ones. The effect of cosolvents on metalloporphyrins is demonstrated to switch the
      reduction of tetrachlorethylene (PCE) from no reaction to complete PCE
      transformation within 24 h and the production of final non-chlorinated compounds.
      Variations in product distributions for the different metalloporphyrins indicate
      that changes in the core metal can influence reaction rates and effective
      pathways. Furthermore, different cosolvents can generate varied product
      distributions, again suggesting that different pathways and/or rates are
      operative in the reduction reactions. Comparison of different cosolvent effects
      on PCE reduction using vitamin B12--a soluble natural metalloporphyrinogen--as
      the catalyst shows less pronounced differences between reactions in various
      cosolvent solutions versus only aqueous solution.

PMID- 15519396
TI  - Chemical stability of chlortetracycline and chlortetracycline degradation
      products and epimers in soil interstitial water.
AB  - Tetracyclines and tetracycline degradation products and epimers end up in the
      environment. In order to predict the persistence of the potential dominating
      species of the chlortetracyclines in the environment, the chemical stability of
      chlortetracycline (CTC) and four major CTC degradation products and epimers (iso
      CTC, 4-epi-CTC, anhydro-CTC, and 4-epi-anhydro-CTC) was studied in milliQ water
      and soil interstitial water (SIW) under environmentally relevant conditions
      (oxygen, light, pH (3-9), and temperature (6 degrees C and 20 degrees C)). The
      chemical stability of the compounds was evaluated by following the decrease in
      amount of parent compound over time. In order to compare the results obtained
      under the varying conditions, apparent pseudo-first-order rate constants (k(obs))
      for the disappearance of the parent compound and corresponding apparent half
      lives were calculated. A statistical evaluation of the data showed that the
      chemical stability of the chlortetracyclines was generally dependent on
      photolysis, temperature, and matrix. The presence or absence of oxygen did not
      influence on the chemical stability. The presence of calcium and magnesium ions
      in SIW is believed to account for the significant differences in half-lives
      between milliQ water and SIW, although numerous of other factors are believed to
      influence as well. Generally, the five compounds were more persistent at pH 3-4
      than at pH above 5.

PMID- 15519397
TI  - Determination of time-dependent partition coefficients for several pesticides
      using diffusion theory.
AB  - Diffusion-retarded partitioning of pesticides with aggregated soils results in a
      time-dependent partition coefficient (Kd') which is different at equilibrium from
      the partition coefficient derived from conventional 24-h batch studies (Kd)
      measured on dispersed soil. An experiment was undertaken to determine the
      importance of Kd' for the prediction of pesticide concentrations in solutions
      bathing artificial soil aggregates and to determine whether diffusion theory
      could accurately predict the concentrations. Two clay soils were mixed with
      polyacrylamide to create artificial aggregates of 0.8, 1.4 and 1.7 cm diameter
      when dry. After saturation, the aggregates were immersed in solutions containing
      isoproturon or a mixture of isoproturon, chlorotoluron and triasulfuron. The
      decline with time of the pesticide concentrations in the bathing solution was
      monitored and the results were compared with predictions from a diffusion-based
      model. The effective diffusion coefficients of the compounds were obtained by
      either fitting the non-linear diffusion model to the data (D(ef)) or by
      independent calculations based on the properties of the compounds and of the
      aggregates (D(ec)). The diffusion model was able to predict the temporal
      variation in pesticide concentrations in the bathing solution reasonably well
      whether D(ef) or D(ec) values were used. However, equilibrium concentrations in
      solution were sometimes overestimated due to increased sorption with time at the
      particle scale. Overall, the ratio between D(ef) and D(ec) ranged from 0.23 to
      0.95 which was a reasonable variation when compared to the range of aggregate
      sizes used in the experiments and of the Kd values of the compounds.

PMID- 15519398
TI  - Sorption of lead in soil as a function of pH: a study case in Mexico.
AB  - Reactions of lead sorption onto soil are largely affected by properties and
      composition of soil and its solution. In this study, the lead sorption onto
      regosol eutric soil from Francisco I. Madero, Zacatecas, Mexico is evaluated at
      different pH values. Soil samples were suspended in lead solutions of 10, 25, 50,
      100, 150, 200, 300, and 400 mg/l (as Pb(NO3)2). The pH was adjusted at 2, 3, 4,
      and 5.5 with nitric acid for each of the lead solution concentrations. In all the
      cases the ionic strength was I=0.09 M with calcium nitrate. The solid-liquid
      ratios were fixed in 1:100 and 1:200 g/ml. The results show that lead sorption
      increases when pH increases. Experimental isotherms were adjusted by both
      Langmuir and Freundlich models. The Langmuir affinity parameter, K, indicates
      that the lead sorption capacity of Francisco I. Madero soils is largely
      perceptible to pH changes.

PMID- 15519399
TI  - Aqueous solubility, Henry's law constants and air/water partition coefficients of
      n-octane and two halogenated octanes.
AB  - New data on the aqueous solubility of n-octane, 1-chlorooctane and 1-bromooctane
      are reported between 1 degree C and 45 degrees C. Henry's law constants, K(H),
      and air/water partition coefficients, K(AW), were calculated by associating the
      measured solubility values to vapor pressures taken from literature. The mole
      fraction aqueous solubility varies between (1.13-1.60)x10(-7) for n-octane with a
      minimum at approximately 23 degrees C, (3.99-5.07)x10(-7) for 1-chlorooctane
      increasing monotonically with temperature and (1.60-3.44)x10(-7) for 1
      bromooctane with a minimum near 18 degrees C. The calculated air-water partition
      coefficients increase with temperature and are two orders of magnitude lower for
      the halogenated derivatives compared to octane. The precision of the results,
      taken as the average absolute deviations of the aqueous solubility, the Henry's
      law constants, or the air/water partition coefficients, from appropriate
      smoothing equations as a function of temperature is of 3% for n-octane and of 2%
      and 4% for 1-chlorooctane and 1-bromooctane, respectively. A new apparatus based
      on the dynamic saturation column method was used for the solubility measurements.
      Test measurements with n-octane indicated the capability of measuring
      solubilities between 10(-6) and 10(-10) in mole fraction, with an estimated
      accuracy better than +/-10%. A thorough thermodynamic analysis of converting
      measured data to air/water partition coefficients is presented.

PMID- 15519400
TI  - Detection of lead-induced oxidative stress in the rat epididymis by
      chemiluminescence.
AB  - It has been shown that lead (Pb) is able to induce lipid peroxidation, one of the
      main manifestations of oxidative stress. In this study we examined the
      relationship between chronic Pb exposure and level of reactive oxygen species
      (ROS) in reproductive system tissues of sexually mature male Wistar rats. One
      group of animals (control, K) was allowed to drink distilled water, the second
      group (Pb) was allowed to drink freely 1% aqueous solution of lead acetate.
      Another groups had a following supplements: rats were allowed to drink distilled
      water containing vitamin C (vit C) at concentration of 500 mg/l or Trolox (a
      vitamin E analog) at concentration of 48 mg/l or vit C (500 mg/l) + Trolox (48
      mg/l). The similar groups among Pb-treated animals were examined after treatment
      with the same vitamins and using the same vitamin doses, dissolved in 1% aqueous
      solution of lead acetate. In all cases the time of drinking was 6 months. It was
      found that lead content in samples of tissues from testis, epididymis and in a
      whole blood in Pb- and Pb with antioxidants treated rats was significantly
      elevated. Chemiluminescence (CL) emitted by the Pb-treated tissues was
      significantly higher when compared to the light emission by tissues isolated from
      the animals of control group. The increase in the CL caused by lead occurs in the
      following increasing order within the studied tissues: cauda of epididymis <
      testis < caput of epididymis (19%, 39% and 51%, respectively). Dietary vit C
      supplementation to the Pb-treated rats for 6 months period decreased the CL from
      caput of epididymis, cauda of epididymis and testis (by 43%, 24%, 39%,
      respectively) more effectively in comparison to the control group (35%, 17%, 33%,
      respectively). Also stronger quenching effect on the light emission from the
      above mentioned tissues after Trolox supplementation was observed in the Pb
      treated group (42%, 21%, 35%, respectively) than in the control group (23%, 13%,
      13% respectively). The combination of both antioxidants treatments (vit C and
      Trolox) did not give a higher significant quenching effect compared to the
      treatment with the vitamins separately. No ultrastructural changes were found in
      the seminiferous epithelium of Pb-treated animals. However, we found
      abnormalities in ultrastructure of epididymal epithelial cells and epididymal
      spermatozoa in rats of Pb-treated groups. These findings provide ex vivo evidence
      that Pb causes oxidative cellular damage in reproductive system tissues of adult
      male rats, which may be closely associated with the ROS production.

PMID- 15519401
TI  - Determination of herbicides in stemflow and throughfall of beeches (Fagus
      sylvatica L.) and in rainfall.
AB  - The pesticide contamination of water samples collected in and nearby a beech
      forest in northern Germany was evaluated. For this purpose, a method for the
      collection of water samples from stemflow and throughfall of beeches (Fagus
      sylvatica L.) and rainfall was developed in response to the demands for the
      analysis of organic contaminants in water samples. Furthermore a sensitive and
      selective multiresidue method was developed to determine 18 pesticides,
      frequently used in Germany, in aqueous samples. The samples collected were taken
      from the stemflow, the crown throughfall and the rainfall between May and
      November 2001. Analysis based on reversed-phase liquid chromatography with a
      pneumatically assisted electrospray mass spectrometer followed a solid phase
      extraction using C-18 extraction cartridges. Isoproturon, metolachlor,
      prosulfocarb and terbuthylazine were found during and shortly after their
      application period. In rainfall metolachlor, terbuthylazine and prosulfocarb were
      detectable in concentrations between 5 and 65 ng l(-1) and isoproturon in
      concentrations between 20 and 360 ng l(-1) respectively. In most of the samples,
      concentrations of those four pesticides were higher and detectable for a longer
      time in stemflow than in rainfall. Crown throughfall samples were collected from
      the end of August to November. Absolute deposition of isoproturon to forest soil
      were up to 70 times higher in comparison to rainwater samples.

PMID- 15519402
TI  - Leaching of brominated flame retardants in leachate from landfills in Japan.
AB  - Leachate samples were taken from seven different landfills and concentrations of
      brominated flame retardants (BFRs), i.e. polybrominated diphenyl ethers (PBDEs)
      and tetrabromobisphenol A (TBBPA), were quantified. Leaching characteristics of
      BFRs, especially factors affecting leachability, were clarified to obtain basic
      information regarding the release of BFRs into the environment. The results
      obtained for observed levels of the sum of PBDE-47, -99 and -100 were n.d.--4000
      pg/l for the raw leachate and n.d. for the treated one, respectively, and those
      of TBBPA were n.d.--620,000 pg/l for the raw leachate and n.d.--11,000 pg/l for
      the treated one, respectively. Three sites that not only had crushed material
      from bulk wastes such as waste electric and electronic equipment, but also were
      under operation or within a year since closure, indicated a higher concentration
      of BFRs than the other sites. In particular extremely high concentration of PBDEs
      was observed at a site with a large amount of organics. Considering the leaching
      characteristics of BFRs, there exists the possibility that leachability of PBDEs
      is influenced by the presence of dissolved humic matter (DHM) in the leachate.
      The high removal efficiency for BFRs in the leachate treatment process was also
      confirmed.

PMID- 15519403
TI  - Acute and chronic effects of clofibrate and clofibric acid on the enzymes
      acetylcholinesterase, lactate dehydrogenase and catalase of the mosquitofish,
      Gambusia holbrooki.
AB  - The objective of this study was to investigate both acute and chronic effects of
      clofibrate and clofibric acid on the enzymes acetylcholinesterase (AChE), lactate
      dehydrogenase (LDH) and catalase (CAT) of the mosquitofish (Gambusia holbrooki).
      AChE, commonly used as a biomarker of neurotoxicity, was determined in the total
      head. LDH, an important enzyme of anaerobic metabolism, was quantified in dorsal
      muscle, and CAT, enzyme which has been used as indicative parameter of peroxisome
      proliferation, was determined in the liver. Furthermore, alterations of body and
      liver weight were also determined, through the calculation of the ratios final
      body weight/initial body weight, liver weight/final body weight, liver
      weight/gills weight and liver weight/head weight. Acute exposure of G. holbrooki
      to both clofibrate and clofibric acid induced a decrease in liver CAT activity,
      an increase in muscle LDH activity, while no effects were observed on AChE
      activity. However, chronic exposure did not alter significantly the enzymatic
      activities, suggesting reduced or null effects over these pathways, relative to
      effects reported in other species. No effects were observed for the calculated
      ratios, except a significant weight reduction for males chronically exposed to
      clofibrate.

PMID- 15519404
TI  - Effects of cadmium and zinc on oxygen consumption, ammonium excretion, and
      osmoregulation of white shrimp (Litopenaeus vannamei).
AB  - White shrimp, Litopenaeus vannamei, a globally important cultured prawn species,
      is an ideal animal for studying the impairment caused by the effects of heavy
      metals that are often detected in coastal areas. The main purpose of the present
      study was to detect the acute toxicity of Cd and Zn to L. vannamei, and to
      investigate their effects on gill functions, which have not been carried out in
      this species before, hoping to obtain some important significance. First of all,
      we examined the acute toxicity of cadmium (Cd) and zinc (Zn) to L. vannamei and
      obtained 24-, 48-, 72-, and 96-h medium lethal concentration (LC50) values of
      2.58, 1.30, 1.14, and 1.07 mgCd l(-1) and 3.98, 2.14, 1.75, and 1.35 mgZn l(-1),
      respectively. Furthermore, we also found that exposure of shrimp to Cd or Zn
      caused an inhibition in oxygen consumption of 91.3% and 75.9% lower than that of
      the control. However, after separate exposure to Cd or Zn, elevations in ammonium
      excretion were obtained, which were 153.7% and 144.1%, respectively, higher than
      the control. It is most likely that elevations in ammonium excretion were related
      to decreased osmotic pressure of shrimp blood. Finally, the distribution of Cd
      and Zn within gills was also determined.

PMID- 15519405
TI  - Sources of variability in plant toxicity testing.
AB  - Published literature is investigated regarding the response of plants to various
      substances to determine the sensitivity of agricultural plants versus other
      species, the similarity of effects seen at different taxonomic levels,
      sensitivity of plants growing outdoors versus in a greenhouse, and the
      sensitivity of different measurement endpoints. We find that agricultural species
      are not consistently more or less sensitive to the herbicides tested than non
      crop species. Genus and family taxonomic groupings may show similar responses
      among species, but this similarity quickly decreases as the comparison progress
      between orders and classes. Results from field and greenhouse studies are less in
      agreement between studies than data from the other topics. Shoot length will be
      affected at concentrations lower than for other vegetative endpoints for most
      species tested for inorganic substances, but for organic substances root and
      shoot mass were more sensitive. Overall, there is no one species or endpoint that
      is consistently the most sensitive for all species or all chemicals in all soils,
      and differences in bioavailability among compounds may confound comparison of
      test results. Therefore, species sensitivity distributions, adjusted for
      bioavailability when possible, should be considered in order to better evaluate
      effects to non-target terrestrial plants.

PMID- 15519406
TI  - Populations, longevity, mortality and fecundity of Chrysoperla carnea
      (Neuroptera, Chrysopidae) from olive-orchards with different agricultural
      management systems.
AB  - The influence that different styles of olive-orchard management (conventional,
      integrated, and organic) exert on the predator Chrysoperla carnea has been
      studied to strengthen this insect's role in the integrated management against
      pests. For this, the adult chrysopid populations were determined by McPhail
      traps, and laboratory examinations were made of certain biological
      characteristics of the first generation of adults captured in each of the olive
      orchards studied. The chrysopid populations increasing significantly during some
      months in the integrated and organic olive orchard. The most abundant species in
      all the zones was C. carnea, representing 95% of all captures in the conventional
      olive orchard. It was found that the larvae from the integrated olive orchard
      took longer to develop, while the pupae from the organic orchard evolved most
      rapidly to adulthood. The highest mortality rate was for larvae in the
      conventional olive orchard. The fecundity of the females from the organic
      orchards was significantly greater, presumably due to their greater longevity and
      shorter pre-oviposition period. These results can be used to improve conservation
      strategies and to increase C. carnea populations and their predatory activity.

PMID- 15519407
TI  - Effects of the endocrine disrupter chemicals chlordane and lindane on the male
      green neon shrimp (Neocaridina denticulata).
AB  - The purpose of this study was to investigate the effect of chlordane and lindane
      on morphological changes and endocrine disruption in male Green neon shrimp
      (Neocaridina denticulata). In this experiment, individuals of N. denticulata, a
      common inhabitant of freshwater systems in Taiwan, were exposed to chlordane (1
      and 10 ng/l and lindane (0.1 and 1 microg/l morphological changes and
      reproductive hormone levels were observed following four weeks exposure.
      According to our findings, an increase in estrogen, a reduction in testosterone,
      and morphological alternations of the masculine appendage were observed in both
      chlordane- and lindane-treated shrimp, while induction of a vitellogenin-like
      protein appeared only in shrimp treated with 10 ng/l chlordane. An endocrine
      disruption effect on N. denticulata was demonstrated, and may apply to other
      organochlorine pesticides or endocrine disruption chemicals.

PMID- 15519408
TI  - Phenotypic plasticity in Scenedesmus incrassatulus (Chlorophyceae) in response to
      heavy metals stress.
AB  - The microalgae genus Scenedesmus is commonly found in freshwater bodies,
      wastewater facilities and water polluted with heavy metals. Phenotypic plasticity
      in Scenedesmus has been documented in response to a wide variety of conditions;
      however, heavy metals have not been comprehensively documented as phenotypic
      plasticity inducers. In this study, we report the phenotypic plasticity of
      Scenedesmus incrassatulus (a non-spiny, four-cell coenobium forming species) in
      response to EC(50) value of copper, cadmium and hexavalent chromium. S.
      incrassatulus was grown in batch cultures in the presence of each metal.
      Chlorophyll-a content, cell size, parameters derived from the schematic energy
      flux model for photosystem II, and morphotype expressions were recorded. Divalent
      cation metals induced unicellular forms, and hexavalent chromium produced out-of
      shape coenobia corresponding to various stages of autospore formation. The
      changes induced by divalent metals were interpreted as phenotypic plasticity,
      because they were always associated to population doublings and were reversible
      when toxicant pressure was removed (only for Cu). Copper was the best inductor of
      unicellular forms and also affected significantly all the photosynthetic
      parameters measured. The developed morphotypes could confer ecological advantages
      to S. incrassatulus in metal stressed environments.

PMID- 15519409
TI  - Nonylphenols in freshwaters of the hydrologic system of an Italian district:
      association with human activities and evaluation of human exposure.
AB  - A sampling campaign for the determination of concentrations of nonylphenol
      isomers (NPs) in freshwaters and sediments of the hydrologic system of the Rieti
      district (central Italy) was conducted from 2002 to 2003. Eighteen sampling
      points, selected on the basis of the different human activities in the vicinity,
      were monitored; six series of water samples (from June 2002 to February 2003) and
      one of sediment samples (summer 2002) were analyzed by GC/MS. There was a direct
      relationship between concentrations of NPs and the presence of urban or
      industrial activities near the sampling point. However, concentrations of NPs in
      water were in the range of < 0.1-1.4 microg l(-1), and their presence limited to
      short distances from the sources of contamination. Accumulation factors in
      sediment samples ranged from 10(2) to 5x10(3).

PMID- 15519410
TI  - Determination of estrogenic activity by LYES-assay (yeast estrogen screen-assay
      assisted by enzymatic digestion with lyticase).
AB  - In order to enhance the sensitivity and the speed of the yeast estrogen screen
      (YES)-assay, which has been established in many laboratories for the
      determination of estrogenic activity of compounds and environmental samples, the
      LYES-assay, a modified version of the YES-assay including a digestion step with
      the enzyme lyticase, was developed. With the LYES-assay the estrogenic activities
      of natural (17beta-estradiol E2 and estrone), synthetic (17alpha-ethinylestradiol
      EE2) and pharmaceutical estrogens (diethylstilbestrol DES) as well as
      xenoestrogens (4-nonylphenol NP and five parabens) were determined and compared
      with the results obtained by other in vitro-assays namely the conventional YES
      assay, the E-Screen-assay (MCF-7 breast tumor cell proliferation) and a receptor
      binding-assay (RB) with human estrogen receptors hER-alpha and hER-beta. In the
      case of E2 the LYES-assay had a significantly lower limit of quantification (LOQ)
      than the conventional YES-assay and even two orders of magnitude lower than the
      RB-assay. Compared to the E-Screen-assay the LOQ of the LYES-assay was almost one
      order of magnitude higher. The time required to perform the LYES-assay was as
      little as seven hours compared to three to five days for the conventional YES
      assay. Thus, the LYES-assay is a very good alternative to existing estrogenic in
      vitro-assays, since it has a good sensitivity, is cheap and much faster than the
      other assays.

PMID- 15519411
TI  - Distribution of mercury in adult penaeid shrimps from Altata-Ensenada del
      Pabellon lagoon (SE Gulf of California).
AB  - The Altata-Ensenada del Pabellon lagoon system is located in the central part of
      Sinaloa state, NW Mexico. The major sources of pollution are represented by the
      waste effluents from the intensive agriculture and the urban sewage from the
      cities of Culiacan (population of 750000) and Navolato (population of 50000). In
      this lagoon system diverse penaeid shrimps occur; the crystal shrimp
      Farfantepenaeus brevirostris, the brown shrimp F. californiensis, the blue shrimp
      Litopenaeus stylirostris, the white shrimp L. vannamei and the Pacific seabob
      Xiphopenaeus kroyeri. With the purpose of knowing distribution and relative
      concentrations of Hg in the main tissues of penaeid shrimps, levels of Hg in five
      species from Altata-Enesenada del Pabellon lagoon on the SE Gulf of California
      were determined. Analysis were carried out by reducing mercury compounds after
      acid digestion reduction with SnCl(2) and detection by cold vapour atomic
      absorption. In general, hepatopancreas was the tissue where Hg was mostly
      accumulated, followed by muscle and exoskeleton. The sequence of Hg
      concentrations in the five species studied here for every tissue was:
      hepatopancreas L. vannamei>F. californiensis>L. stylirostris>F. brevirostris>X.
      kroyeri; muscle L. stylirostris>F. brevirostris>L. vannamei>F. californiensis=X.
      kroyeri and exoskeleton F. brevirostris>F. californiensis>L. vannamei>L.
      stylirostris>X. kroyeri.

PMID- 15519412
TI  - Response of antioxidants in sunflower (Helianthus annuus L.) grown on different
      amendments of tannery sludge: its metal accumulation potential.
AB  - The interaction of metals present in tannery waste and their tolerance in the
      plants of sunflower (Helianthus annuus L.) was studied in the present paper under
      field conditions. Effects of 100% tannery sludge and various amendments of
      tannery sludge (10%, 25%, 35%, 50%, 75%) along with one set of control were
      studied on the physiological and biochemical parameters of the plant along with
      their metal accumulation potential after 30, 60 and 90d after sowing. The plants
      of H. annuus were found effective in the accumulation of metals (Cr, Fe, Zn and
      Mn) in roots, shoots and leaves, however, the level of toxic metal, Cr was found
      below detection limit in the seeds of the plant. The oil was extracted from the
      seeds of the plant and the level of oil content was increased up to 35% tannery
      sludge as compared to control followed by decrease at higher tannery sludge
      ratio. An increase in the chlorophyll, protein, cysteine, non-protein thiol and
      sugar contents was observed at the lower amendment of tannery sludge at initial
      exposure periods followed by decrease than their respective controls.
      Malondialdehyde content in the roots and leaves was increased beyond 50% sludge
      amendments at all the exposure periods as compared to control. However, proline
      and ascorbic acid contents of the roots and leaves of the plant increased at all
      the exposure periods and sludge amendments, compared to their respective
      controls.

PMID- 15519413
TI  - Toxicological and biochemical responses of the earthworm Lumbricus rubellus to
      pyrene, a non-carcinogenic polycyclic aromatic hydrocarbon.
AB  - The effects of the polycyclic aromatic hydrocarbon (PAH) pyrene on earthworms
      were investigated in contact and soil tests. In addition to measuring toxic
      effects on survival and reproduction, Ethoxyresorufin-o-deethylase (EROD)
      activity and catalase activity were also studied as possible biomarkers of toxic
      stress. The survival data indicated that LC50 values were 0.0068 mg/ml for the
      contact test, and 283 mg/kg in the soil test. Cocoon production rate was
      significantly reduced compared to controls at 160, 640 and 2560 mg/kg in the soil
      test. No EROD activity could be detected in preliminary studies using control and
      exposed animals from the contact test, so this assay was not used to the soil
      test. Catalase activity was shown to be significantly lower at 640 mg/kg in the
      soil test compared to all other treatments and the control. When compared to
      toxicological data for other soil invertebrates, Lumbricus rubellus has an
      intermediate sensitivity in respects of survival and a lower sensitivity for
      reproductive effects, although the soil used in this study had a higher organic
      content than previous studies, meaning that the sensitivity of this species may
      be underestimated in comparison to previous published data for other soil
      invertebrates.

PMID- 15519414
TI  - Postmetamorphic Xenopus laevis shows decreased plasma triiodothyronine
      concentrations and phosphorylase activity due to subacute phytosterol exposure.
AB  - Postmetamorphic South African clawed frogs (Xenopus laevis) were exposed to a
      phytosterol mixture (ca. 80% beta-sitosterol and less sitostanol, campesterol,
      and campestanol) for 14 days at 30 mugl(-1) in a flow-through system. The effects
      of phytosterols (PS) on the plasma thyroid hormone (T(3) and T(4)), testosterone,
      leptin-immunoreactive peptide and tissue glycogen concentrations were determined.
      The following enzyme activities were also analyzed from the liver and muscle:
      glycogen phosphorylase and lipase, and from the liver only: glucose-6
      phosphatase. The plasma T(3) concentration was lower in the PS-exposed female
      frogs. Both muscle lipase and glycogen phosphorylase activities were also lower
      in the PS-exposed animals. These results could indicate that the basal metabolic
      rate and locomotion activity of the frogs were decreased. The effects could not
      be attributed to the possible estrogenicity of the PS mixture. Further studies
      will be needed to evaluate the possible significance of these effects.

PMID- 15519415
TI  - Dynamics of fipronil residue in vegetable-field ecosystem.
AB  - Fipronil insecticide has been widely used to control vegetable pests in China
      recently. The research was conducted to evaluate the fate of fipronil in
      vegetable-field ecosystem and provide the scientific basis of using this
      insecticide. Developed on the analytical methods of fipronil residue and its four
      metabolisms, the degradation dynamics of their residue in a vegetable and the
      soil of the vegetable fields was studied. The results showed that (1) degradation
      of fipronil was faster in pakchoi (half-life 2.6 days) than in soil (half-life
      7.3 days); (2) degradation reaction occurred in soil was governed mainly by
      photodegradation and oxidization accompanying with production of the metabolites,
      MB46513 and MB46136. Reduction and hydrolyzation played little role in the
      degradation process. In pakchoi, degradation was mainly contributed by reduction
      though oxidization and hydrolyzation occurred simultaneously. The metabolite
      products were MB45950, MB46136 and RPA200766; (3) the final residue in pakchoi
      was at a level of 0.003 mg kg(-1), which was much lower than the USA's upper
      limit of 0.04 mg kg(-1) in rice. Therefore, a dosage of 24 g hm(-2) was suggested
      and considered as safe to human beings and animals.

PMID- 15519416
TI  - Evaluation of approaches for terrestrial hazard classification.
AB  - Hazard assessment is an essential element in the evaluation of the potential
      effects of chemical substances on the environment. To date, most work has focused
      on hazard assessment schemes for the aquatic environment, but in recent years, a
      number of proposals have been developed for other environmental compartments. Due
      to limited datasets, the suitability of the toxicity cut-off values in these
      schemes has not been fully determined and the practicalities associated with
      using these approaches have not been fully established. This study, which focused
      on the soil compartment, was performed to examine cut-off values proposed by two
      terrestrial hazard assessment schemes and establish the availability of data.
      Data on earthworms indicated that current proposals for toxicity cut-off values
      are appropriate. However, analysis of IUCLID (International Uniform ChemicaL
      Information Database) indicates that even for commonly used high production
      volume chemicals, insufficient data are available to enable classification.
      Whilst the necessary data may already be available for selected groups of
      substances (e.g. pesticides and veterinary medicines), a significant experimental
      testing programme would therefore be required before a terrestrial classification
      system could be applied widely. Such data may become available in the future as a
      result of initiatives such as REACH.

PMID- 15519417
TI  - Changes in water quality after addition of sea salts to fresh water: implications
      during toxicity testing.
AB  - Sea salts (seven brands from six commercially-available sources) were dissolved
      in water to develop 30 g/l solutions, and selected water quality characteristics
      were then monitored for 96 h. One or more water quality characteristics changed
      significantly during the 96 h period in six of the reconstituted sea salts.
      Measured characteristics of sea water diluted to 30 g/l demonstrated no changes
      during the observation period. The sea salts from different sources also
      demonstrated differences in absolute concentrations of some characteristics
      measured. Application of the Biotic Ligand Model to predict copper toxicity to
      the bivalve Mytilus edulis in solutions of the salts tested yielded 96-h median
      lethal concentrations that ranged from 2 to 13 microg/l. Since water quality
      affects toxicity of many environmental pollutants, the source of the sea salt and
      equilibration time should be considered when planning toxicity tests.

PMID- 15519418
TI  - Testing sediment biological effects with the freshwater amphipod Hyalella azteca:
      the gap between laboratory and nature.
AB  - The freshwater amphipod, Hyalella azteca, is widely used in laboratory sediment
      toxicity and bioaccumulation tests. However, its responses in the laboratory are
      probably very different from those in the field. A review of the literature
      indicates that in its natural habitat this species complex is primarily
      epibenthic, derives little nutrition from the sediments, and responds primarily
      to contaminants in the overlying water column (including water and food), not
      sediment or porewater. In laboratory sediment toxicity tests H. azteca is
      deprived of natural food sources such as algal communities on or above the
      sediments, and is subjected to constant light without any cover except that
      afforded by burial into the sediments. Under these constraining laboratory
      conditions, H. azteca has been reported to respond to sediment or porewater
      contamination. In nature, contamination of overlying water from sediment is less
      likely than in the laboratory because of the large, generally non-static sink of
      natural surface water. H. azteca does not appear to be the most appropriate test
      species for direct assessments of the bioavailability and toxicity of sediment
      contaminants, though it is probably appropriate for testing the toxicity of
      surface waters. Toxic and non-toxic responses will be highly conservative, though
      the latter are probably the most persuasive given the exposure constraints. Thus
      H. azteca is probably a suitable surrogate species for determining sediments that
      are likely not toxic to field populations; however, it is not suitable for
      determining sediments that are likely toxic to field populations.

PMID- 15519419
TI  - Comparative toxic effects of formulated simazine on Vibrio fischeri and gilthead
      seabream (Sparus aurata L.) larvae.
AB  - The use of Early Life Stage (ELS) tests is a useful tool in risk assessment. The
      purpose of this study was to compare the sensitivity of the seabream (Sparus
      aurata) larvae with the extensively used Microtox test on a commercial
      formulation containing simazine, an s-triazine herbicide. To this end, survival,
      growth and histopathological changes displayed by seabream yolk sac larvae
      exposed during 72 h post-hatching to nominal concentrations of the commercial
      preparation up to its saturating concentration in water, and bioluminescence of
      the marine bacteria Vibrio fischeri (Microtox) were studied. Survival of larvae
      after three days of exposure was significantly reduced in the highest (4.5 mg/l)
      concentration, but no effects on growth were found in any of the simazine
      treatments. The 72 h LC50 value for yolk sac larvae was estimated as 4.19 mg/l.
      Commercial grade simazine did not exert any significant toxicity to the marine
      bacterium V. fischeri at the concentrations tested.

PMID- 15519420
TI  - Evaluation of antimicrobial agents for veterinary use in the ecotoxicity test
      using microalgae.
AB  - The influence of antimicrobial agents approved as veterinary drugs in Japan on
      the growth of green algae, Selenastrum capricornutum and Chlorella vulgaris, was
      studied in accordance with the OECD guidelines for testing chemicals. Among the
      agents tested, growth inhibitory activity was very varied, i.e. erythromycin
      showed the strongest activity (EC50, 50% effective concentration, = 0.037 mg/l),
      sulfa drugs had activity to some extent (EC50s of sulfamethoxazole, sulfadiazine,
      and sulfadimethoxine were 1.5, 2.2, and 2.3 mg/l, respectively), but ampicillin
      and cefazolin did not inhibit growth (EC50s>1000 mg/l). We also investigated
      synergistic effect of combining sulfa drugs with trimethoprim or pyrimethamine,
      which are commonly used as a combined drug. By adding trimethoprim, the growth
      inhibitory activity of sulfamethoxazole and sulfadiazine was significantly
      enhanced. Growth inhibition by sulfa drugs was reduced by the addition of folic
      acid, indicating that they inhibit folate synthesis in green algae.

PMID- 15519421
TI  - Holographic QSAR of selected esters.
AB  - The HQSAR (Holographic QSAR) method, which has been recently developed, can offer
      the ability to rapidly and easily generate QSAR models of high statistical
      quality and predictive value. HQSAR analysis requires selecting values for
      parameters that specify the size of the hologram that is to be used, and the size
      and type of fragment substructures that are to be encoded. The color coding is
      provided by HQSAR to reflect which molecular fragments may be important
      contributors to the biological activity. In this work, we studied the
      quantitative structure activity relationship of selected esters using the HQSAR
      method. A robust HQSAR model with r(2) (non-cross-validated regression
      coefficient) of 0.981 and q(2) (cross-validated regression coefficient) of 0.912,
      was developed after optimizing the fragment size and the hologram length. The
      color coding analysis, which has rarely been reported before, was done here to
      explain the outlier successfully.

PMID- 15519423
TI  - First- and midtrimester Down syndrome screening and detection.
AB  - Overall, Down syndrome detection capabilities have improved remarkably over the
      last 2 decades. Widely practiced first-trimester screening and less extensively
      elevated midtrimester urine screening promise even greater accuracy than was
      available a decade ago. Recently, the combination of first- and second-trimester
      screening has been reported to enhance discrimination of the Down syndrome fetus
      from normal cases. Although the advances are welcome, they present the
      significant prospect of multiple competitive algorithms with the risk of
      confusing patients, practitioners, and health care planners. The need for
      reasonable consensus has never been more pressing.

PMID- 15519424
TI  - Controversies regarding cervical incompetence, short cervix, and the need for
      cerclage.
AB  - Cervical incompetence (CI) is not an all or nothing phenomenon but a continuous
      variable. CI and preterm labor are not distinct entities but rather part of a
      spectrum leading to preterm delivery. Cervical length (CL) is an independent
      variable in the prediction of preterm delivery, to which it is inversely related.
      Application of a primary transvaginal cervical cerclage appears to be an
      unnecessary intervention in about 50% of women presenting with a history
      suggesting cervical incompetence. A better alternative for women with a history
      of or risk factors for CI is transvaginal ultrasonographic follow-up of CL. To
      facilitate the comparison of studies of CI, the authors suggest a nomenclature
      reflecting the different stages of prevention: primary, secondary, and tertiary
      transvaginal cervical cerclage.

PMID- 15519425
TI  - Prevention and management of RhD isoimmunization.
AB  - An Rh-negative woman is at risk for developing Rh isoimmunization upon exposure
      to RhD antigens from her Rh-positive baby through fetal-maternal hemorrhage. The
      incidence of Rh isoimmunization and fetal hemolytic disease has decreased
      substantially since Rh immune globulin was introduced in 1968. When RhD
      sensitization does occur, careful follow-up of these mothers and judicious
      intervention can result in good outcomes for most pregnancies. Both Doppler
      assessment of middle cerebral artery peak systolic velocity and spectral analysis
      of amniotic fluid at 450 nm (DeltaOD 450) are useful in the diagnosis and
      management of fetal anemia.

PMID- 15519426
TI  - Diagnosis and management of intrauterine growth restriction.
AB  - The growth-restricted fetus is a fetus who fails to reach his growth potential
      and is at risk for perinatal morbidity and mortality. When a fetus has an
      estimated weight below the 10th percentile, in the absence of congenital
      anomalies and in the presence of a normal amount of amniotic fluid, Doppler
      velocimetry gives the most important information to differentiate the truly
      growth-restricted fetus from the fetus that is constitutionally small but
      otherwise normal. One area of debate and research is whether Doppler velocimetry
      can help in timing the delivery of the growth-restricted fetus. Data appear to
      support the use of ductus venosus velocimetry in deciding when to deliver, but
      randomized data on this point are still lacking.

PMID- 15519427
TI  - Preterm premature rupture of the membranes: diagnosis and management.
AB  - Preterm premature rupture of the membranes (preterm PROM) is a common and
      significant cause of preterm birth and perinatal morbidity and mortality. The
      obstetric caregiver has the opportunity significantly to alter pregnancy and
      perinatal outcome for women suffering from this complication. Although management
      is often predetermined by the presence of clinical infection, vaginal bleeding,
      labor, or nonreassuring fetal heart-rate pattern on admission, a gestational age
      based approach to the management of the stable patient with preterm PROM offers
      the potential to reduce perinatal infectious and gestational age-dependent
      morbidity for patients who are amenable to conservative management.

PMID- 15519428
TI  - Screening and management of inherited thrombophilias in the setting of adverse
      pregnancy outcome.
AB  - Inherited thrombophilic conditions are associated with adverse pregnancy
      outcomes, including severe pre-eclampsia, fetal loss, abruptio placentae, and
      intauterine growth restriction. Although the prevalence of these complications is
      approximately 8% in the general population, their presence is associated with a
      significantly increased recurrence risk. Thrombophilic conditions most strongly
      associated with adverse pregnancy outcome include factor V Leiden, prothrombin
      gene mutation, and deficiencies of protein S, protein C, and antithrombin. Other
      thrombophilic conditions, such as protein Z deficiency, also appear to be
      associated with an increased risk of pregnancy complications. Antenatal
      administration of heparin to prevent pregnancy complications has shown promise in
      small studies, but a randomized, placebo-controlled trial is necessary to
      determine whether heparin administration is beneficial in preventing adverse
      pregnancy outcome.

PMID- 15519429
TI  - Diagnosis and management of hemolysis, elevated liver enzymes, and low platelets
      syndrome.
AB  - Pregnancies complicated by hemolysis, elevated liver enzymes, and low platelets
      (HELLP) syndrome require a well-formulated management plan. The development of
      this syndrome after 34 weeks' gestation or with documentation of maternal or
      fetal compromise is an indication for delivery. Acute fatty liver of pregnancy,
      hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura may present
      with signs, symptoms, and laboratory abnormalities that may be confused with
      HELLP syndrome. Thorough investigation is warranted because of the differences in
      proper management among these various complications of pregnancy. Expectant
      management in patients with HELLP syndrome remote from term and the use of
      corticosteroids to improve postpartum maternal outcome remain experimental.

PMID- 15519430
TI  - Imitators of severe pre-eclampsia/eclampsia.
AB  - Several microangiopathic disorders that are encountered during pregnancy provide
      physicians with a formidable diagnostic challenge. Severe pre-eclampsia with
      hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome and many
      other obstetric and medical or surgical conditions produce similar clinical
      presentations and laboratory study results to pre-eclampsia. Pre-eclampsia is
      frequently superimposed on one of the above disorders, further confounding an
      already difficult differential diagnosis. Because of the remarkably similar
      clinical and laboratory findings of these disease processes, even the most
      experienced physician will face a diagnostic challenge. An effort should be made
      to make an accurate diagnosis, given the fact that management strategies and
      outcome may differ among these conditions.

PMID- 15519431
TI  - Diagnosis and management of women with stroke during pregnancy/postpartum.
AB  - Although the incidence of stroke is extremely low, the complications are serious.
      Maternal mortality has been reported to be as high as 26%. It is important for
      doctors to be aware of the causes, diagnostic techniques, and management
      strategies for stroke in order to achieve the best outcome for the mother and
      fetus. Recurrence risk appears extremely low, so women should feel confident in
      future positive pregnancy outcomes.

PMID- 15519432
TI  - Sexual knowledge and emotional reaction as indicators of sexual abuse in young
      children: theory and research challenges.

PMID- 15519433
TI  - Child maltreatment and perceived family environment as risk factors for adult
      rape: is child sexual abuse the most salient experience?
AB  - OBJECTIVE: Child maltreatment and family functioning were examined as predictors
      of adult rape in a sample of 925 college women. METHOD: Information was obtained
      from retrospective self-report questionnaires. Child sexual abuse (CSA) was
      assessed with the Life Experiences Questionnaire, child emotional abuse (CEA) and
      physical abuse (CPA) were assessed with the Childhood Trauma Questionnaire,
      family functioning was assessed with the Family Environment Scale, and adult rape
      was assessed with the Sexual Experiences Survey. RESULTS: Approximately 17% of
      women reported a history of any form of child abuse: 8.9% reported CSA, 4.2%
      reported CPA, and 8.6% reported CEA. Fifteen percent of participants reported a
      history of rape since age 17. CSA and CEA, but not CPA, were related to adult
      rape. Experiencing multiple forms of child abuse increased the risk of adult
      rape. Logistic regression analyses indicated that CSA predicted adult rape
      (OR=1.9). Further, low levels of family cohesion predicted adult rape only in the
      absence of CEA (OR=1.2), and low levels of emotional expressiveness in the family
      predicted adult rape only in the presence of CEA (OR=1.4). CONCLUSIONS: Findings
      highlight the need to consider multiple forms of child abuse as well as family
      functioning in relation to the risk of adult sexual victimization. Findings
      suggest CSA is a risk factor for adult victimization independent of family
      functioning, and family dysfunction exerts an impact on rape only in relation to
      CEA.

PMID- 15519434
TI  - Adolescents who experienced sexual abuse: fears, needs and impediments to
      disclosure.
AB  - OBJECTIVE: Understanding the impediments that prevented sexually abused
      adolescents from disclosure to their family or to professionals, and analyzing
      the responses they received when they did disclose. METHODS: In depth anonymous
      interviews were conducted in Italy through a toll-free telephone line with 36
      young people who experienced sexual abuse in adolescence. A qualitative analysis
      was carried out of the adolescents' feelings, fears and needs, and of the help
      received, if any. RESULTS: The main impediments to disclose to a family member
      were fear of not being believed, shame, and fear of causing trouble to the
      family. The main impediments for not seeking services were ignorance of the
      existence/functioning of protective agencies, wish to keep the secret, lack of
      awareness of being abused, mistrust of adults and professionals, and fear of the
      consequences of disclosure. When they did disclose to professionals, the teens
      received very limited support. CONCLUSION: Adolescents need to receive proper
      information about the risk of being sexually abused and about the help they can
      receive from their social network and protective agencies. There is a crucial
      need for appropriate training of professionals.

PMID- 15519435
TI  - Childhood trauma and adult interpersonal functioning: a study using the Core
      Conflictual Relationship Theme Method (CCRT).
AB  - OBJECTIVE: This study aimed to examine the long-term correlates of childhood
      trauma in regard to interpersonal functioning in adulthood. METHOD: One hundred
      and nineteen (N=119) subjects from the Austen Riggs Follow-along Study were
      included in the study. The Traumatic Antecedent Interview scoring method was used
      to assess 10 types of childhood trauma. Two additional positive variables were
      also assessed. Interpersonal patterns in adulthood were assessed using the Core
      Conflictual Relationship Theme Method. RESULTS: Subjects reporting childhood
      physical abuse had a higher prevalence of the wish to be hurt, and experienced
      others as strict and stern. Those reporting physical neglect had a higher
      prevalence of the need to be comforted. Subjects who had experienced significant
      separations during childhood later felt less self-confident in interpersonal
      situations. Results also showed that subjects who had access to a
      caretaker/confidant had less need for love. A number of additional findings were
      nominally significant but did not remain so after correction for multiple
      comparisons. CONCLUSIONS: The findings indicate that internalized thoughts and
      affects regarding childhood traumatic events may still play a role long after the
      time period of the events. Results also suggest that a continuous measurement
      approach to the study of traumata may provide information not captured by a
      dichotomous approach.

PMID- 15519436
TI  - Self-perceived peer harassment in a community sample of Norwegian school
      children.
AB  - OBJECTIVE: The experience of being harassed is associated with various forms of
      maladjustment. This study examined the prevalence of three domains of harassment,
      and their associations with emotional and behavioral problems. METHOD: A total of
      4130 young people in 6th through 10th grade in 66 primary and secondary schools
      in Norway completed questionnaires on self-perceived harassment and emotional and
      behavioral problems. RESULTS: The structural psychometric properties of the
      scales of harassment showed an acceptable fit to the data. Boys reported more
      harassment on all items and domains than girls across grades. Strong associations
      between self-perceived harassment and psychiatric impact and behavioral and
      emotional problems, especially peer problems and conduct disorder, were revealed.
      DISCUSSION: The study adds to the understanding of the concept of harassment and
      its correlations with emotional and behavioral problems. The study underscores
      the importance of conducting routine screening in school as an important basis
      for the subsequent improvement in children's relationships.

PMID- 15519437
TI  - The effects of the Webster-Stratton parenting program on maltreating families:
      fostering strengths.
AB  - OBJECTIVE: This study examined the effects of the Webster-Stratton parenting
      program on the parenting skills of maltreating mothers and on the autonomy of
      their children (3-8 years). METHOD: A randomized controlled trial was used.
      Twenty-six maltreating families were randomly assigned to one of two conditions:
      the 16-hour weekly intervention group, or the 4-month wait list control group.
      Pre- and post-intervention independent assessments included a 2-hour home visit
      involving videotaped mother-child interactions during two prescribed, 10-minute
      play activities. RESULTS: Compared to the control group, treatment mothers
      demonstrated significant improvement in involvement and marginally significant
      improvement in autonomy-support, but no improvement in structure. Treatment group
      children showed no significant improvement in autonomy when compared to control
      group children. CONCLUSIONS: This parenting program proved effective with
      maltreating parents. The lack of demonstrated effect on children may reflect the
      need for a larger and more sustained treatment dose and/or the need to include
      parent-child interaction opportunities in the program. At the same time, while
      treatment gains were limited to the parent, the high treatment adherence rate
      (92% attended six or more of the eight program sessions) and low attrition rate
      (n=1) indicate that the treatment gains may hold potential for more thorough
      examination.

PMID- 15519438
TI  - Abusive head trauma in young children: characteristics and medical charges in a
      hospitalized population.
AB  - OBJECTIVE: To describe the presenting characteristics, hospital course, and
      hospital charges associated with hospital admissions for head trauma in young
      children at a regional pediatric trauma center, and to examine whether these
      factors differ among abused and non-abused subjects. METHOD: Comparative case
      series study involving a retrospective medical record review of children less
      than 3 years of age admitted to Children's Hospital of Pittsburgh from January 1,
      1995 to December 31, 1999. Subjects (n=377) were identified on the basis of ICD-9
      CM codes for head injury. Subjects were classified as abused or non-abused based
      on standard criteria using information about the type of injuries, the history
      provided by the caretaker, and physical and radiographic findings. RESULTS:
      Eighty nine (23.6%) subjects were classified as abused and 288 (76.4%) were
      classified as non-abused. Abused subjects were more likely then non-abused
      subjects to be <1 year of age (vs. >1 year of age) (OR: 9.8; 95% CI: 5.0, 19.2),
      covered by Medicaid (vs. commercial insurance) (OR: 2.8; 95% CI: 1.7, 4.8), and
      admitted to the ICU (OR: 3.5; 95% CI: 2.1, 5.8; p<.001). The caretakers of abused
      subjects were more likely to give a history of no trauma or minor trauma compared
      to the caretakers of non-abused subjects (97% vs. 54%, p<.001). Length of stay
      was significantly greater for abused subjects versus non-abused subjects (mean:
      9.25 days vs. 3.03 days, p<.001). Hospital charges (1999 dollars) were
      significantly higher for abused (mean+/-SD: 40,082 dollars +/- 58,004 dollars)
      versus non-abused (mean +/- SD: 15,671 dollars +/- 41,777 dollars) subjects.
      CONCLUSIONS: These results highlight the differences in the demographics,
      presenting characteristics and economic impact of abusive head injuries compared
      to non-abusive head injuries.

PMID- 15519439
TI  - Child protection: a neglected area of pediatric residency training.
AB  - BACKGROUND: Child maltreatment is prevalent in Canadian society, and medical
      professionals are frequently required to provide care in these cases. Physician
      knowledge and training in child protection have been questioned. This study
      examined the experience, perceived adequacy of training, and perceived competency
      of Canadian pediatric residents in child protection. METHODS: Structured
      questionnaires were sent to child protection program directors (CPPDs), pediatric
      program directors (PPDs) and pediatric residents at the 16 Canadian pediatric
      academic centers. Data were analyzed using descriptive statistics, chi(2)
      analyses, a Mann-Whitney test, and linear regression. RESULTS: Responses were
      obtained from 15 of 16 CPPDs, all 16 PPDs, and 190 of 348 (54.6%) residents. All
      programs provided didactic teaching sessions. Only 3 programs had mandatory
      clinical rotations, 9 programs offered clinical electives, and 7 programs did not
      offer any specific clinical experience in child protection. Half of the residents
      had seen 5 or fewer cases of maltreatment. Residents and program directors most
      commonly rated the training as "somewhat adequate, needs improvement" with a
      significant minority rating it as "poor, inadequate." Residents' self-rating of
      competency was positively associated with number of years of training and number
      of cases of maltreatment seen. Almost all residents (92%) felt that they needed
      further training in child protection, including 85% of graduating residents. Some
      of the residents (16.4%) did not anticipate dealing with child protection cases
      as practicing pediatricians. CONCLUSIONS: Canadian pediatric residents receive
      little exposure and limited training in child abuse and neglect. As a result,
      even senior pediatric residents feel poorly trained. These results highlight the
      need to establish effective training programs for residents in child protection.

PMID- 15519440
TI  - What's wrong with nursing education research?

PMID- 15519441
TI  - Problem solving strategies integrated into nursing process to promote clinical
      problem solving abilities of RN-BSN students.
AB  - A set of problem solving strategies integrated into nursing process in nursing
      core courses (PSNP) was developed for students enrolled in a post-RN
      baccalaureate nursing program (RN-BSN) in a university in Taiwan. The purpose of
      this study, therefore, was to evaluate the effectiveness of PSNP on students'
      clinical problem solving abilities. The one-group post-test design with repeated
      measures was used. In total 114 nursing students with 47 full-time students and
      67 part-time students participated in this study. The nursing core courses were
      undertaken separately in three semesters. After each semester's learning,
      students would start their clinical practice, and were asked to submit three
      written nursing process recordings during each clinic. Assignments from the three
      practices were named post-test I, II, and III sequentially, and provided the data
      for this study. The overall score of problem solving indicated that score on the
      post-test III was significantly better than that on post-test I and II, meaning
      both full-time and part-time students' clinical problem solving abilities
      improved at the last semester. In conclusion, problem-solving strategies
      integrated into nursing process designed for future RN-BSN students are
      recommendable.

PMID- 15519442
TI  - Evaluation of a mentorship programme for specialist practitioners.
AB  - Health care professionals moving from general care to specialist cancer and
      palliative care face many challenges during their role transition. Mentorship has
      been identified as an effective support mechanism during role transition and the
      Macmillan National Institute of Education devised and piloted a mentorship
      training programme to enable established specialist practitioners to support new
      practitioners through their transition into specialist practice. The 12-month
      programme consisted of a two day workshop and continued support for mentors using
      action learning groups. The pilot programme was evaluated to identify whether or
      not it was meeting the needs of mentors and mentees. Using a self-report
      questionnaire comprising open and closed questions the programme was evaluated
      from the perspective of mentors, mentees, line managers and Macmillan service
      development managers. Results demonstrated that there was a shared belief that
      the presence of a mentor was important during role transition, and that the
      programme was effective in preparing and supporting mentors for their role. As
      new practitioners were supported in role transition there were identified
      benefits for service development. The programme was evaluated positively in
      respect of both the two day workshop and the action learning groups.

PMID- 15519443
TI  - Approaches to learning of student nurses.
AB  - This paper presents findings from a study of student nurses' learning styles in
      an Institution of Higher Education in South Wales, United Kingdom (UK). The aim
      of the research was to evaluate students' approaches to learning as measured by a
      study process questionnaire (SPQ). The questionnaire is viewed as a reliable and
      valid measure of students' learning, and has been used extensively with students
      in higher education in Australia. The SPQ is a 42-item questionnaire measuring
      surface, deep and achieving approaches to learning. It was distributed to 300
      student nurses attending the common foundation program of a preregistration
      nursing course. Data were entered into SPSS Windows Release 10. The results
      indicated that many of the students were taking a surface approach or surface
      achieving approach to their studies. There was little difference in results
      between undergraduates and diploma students or between students majoring in
      different nursing specialties. The deep and achieving approaches to learning
      scores correlated positively and significantly with overall mean assessment
      scores of students, the deep approach with Sociology scores and negatively and
      significantly with Psychology scores. The implications of these results are
      discussed in relation to curriculum design and the demands of higher education.

PMID- 15519444
TI  - Academic freedom, analysis, and the Code of Professional Conduct.
AB  - Despite nursing's move into higher education, academic freedom has received
      little attention within the literature. After discussing the concept of academic
      freedom, this paper argues that there is a potential tension between academic
      freedom and the requirement to educate student nurses who are fit for practice.
      One way in which this tension might be revealed is in the marking of student
      assignments. We ask the question--how should nurse educators mark an essay which
      is sufficiently analytical but reaches moral conclusions that lie outside the
      Code of Professional Conduct? We argue that despite an understandable temptation
      to penalise such an essay, invoking the Code of Professional Conduct to do so, no
      penalty should be applied, and academic freedom for students within higher
      education should be encouraged. This is because first, academic freedom is a good
      in itself especially as it allows unconventional and unpalatable conclusions to
      be discussed and rebutted, and second, applying a penalty on these grounds is
      necessarily inconsistent.

PMID- 15519445
TI  - Reflective learning with drama in nursing education--a Swedish attempt to
      overcome the theory praxis gap.
AB  - It is obvious that the gap between theory and praxis in nursing education affects
      the students' ability to develop understanding and professional knowledge that
      stems both from theory and practice. Appropriate didactic methods are thus needed
      in nursing education. In a project we developed and practised a didactic model
      with the intention of encouraging a reflective attitude within the student,
      considering caring science in theory as well as in praxis. The didactic model,
      based on educational drama, was implemented during three terms of the nursing
      education programme. In this paper we present the educational model and its
      theoretical foundation. We also present the preliminary outcomes of the project.

PMID- 15519446
TI  - Negotiating socialisation: the journey of novice nurse academics into higher
      education.
AB  - In this paper we seek to explore the socialisation process experienced by novice
      nurse academics when they make the transition from the health sector into the
      education sector. We will do this by identifying the theoretical tensions between
      individual freedom in the context of organisational needs. The ramifications of
      these tensions will be highlighted and solutions for raising awareness as to how
      to manage them are discussed. We conclude that a socialisation process that
      protects individual freedom and promotes self-development is one that carries the
      greatest benefit for the novice nurse academic and the educational institution.

PMID- 15519447
TI  - Curriculum changes and moral issues in nursing education.
AB  - Through history nursing education has strongly advocated the importance of
      educating students towards moral and ethical responsibility. In today's society
      however, it has become increasingly difficult to honour this concern. One
      peephole to capture the ongoing struggle is to look into the curriculum where
      different stakeholders voice different opinions. Following a social constructive
      perspective the curriculum texts represent specific interest among stakeholders
      related to nursing education in a certain historical periods. By analysing the
      two last versions of the curriculum we get an insight into moral and ethical
      issues at stake and different ways of addressing these questions. While moral and
      ethical issues in the curriculum of 1987 follow a disciplinary discourse
      emphasising the importance of learning ethical concepts and modes of arguments,
      the curriculum of 2000 places ethical and moral issues within an employability
      discourse. In this curriculum moral issues are seen as an obligation linked to
      students practical and technical skills. The 2000 curriculum represents a shift
      from emphasising the independent and reflective professional to underline the
      skillful and morally obliged practitioner.

PMID- 15519448
TI  - What 'really' affects health professions students' satisfaction with their
      educational experience? Implications for practice and research.
AB  - Student satisfaction has been widely recognised as an indicator of the quality of
      the students' learning and teaching experience. The aim of the study was to
      explore the extent to which student satisfaction is influenced by 13 demographic-
      and educational-related variables. A cross-sectional survey was undertaken (18
      item questionnaire, 1660 questionnaires). Principal component analysis
      categorised the 18 items into four learning and teaching dimensions. Each of the
      13 variables was analysed for its influence on student satisfaction generally and
      on the four dimensions individually, before and after controlling for all the
      other variables. After controlling for all the variables, none of the demographic
      characteristics was associated with satisfaction. Most of the educational
      variables exercised their own independent and significant effects on general
      satisfaction and on satisfaction with the four individual dimensions.
      Collectively, decreased satisfaction was associated with being a pre
      registration, full-time student, usually with A level entry qualifications,
      attending term two modules whose assessment/s comprised combined strategies.
      Decreased satisfaction was also significantly associated with larger class sizes
      as regards the student numbers and with attaining lower grades in the
      assessments. The demographic variables were not as influential as the educational
      ones as regards the affects on students' satisfaction. The implications of the
      findings for research and practice are discussed.

PMID- 15519449
TI  - Evaluation of an assertiveness training program on nursing and medical students'
      assertiveness, self-esteem, and interpersonal communication satisfaction.
AB  - This study's objective was to evaluate the effect of an assertiveness training
      program on nursing and medical students' assertiveness, self-esteem, and
      interpersonal communication satisfaction. Using a longitudinal research design,
      69 participants whose scores on the Assertive Scale were < or = 50% (i.e., low
      assertiveness) and who were willing to participate were included and assigned to
      an experimental group (33 subjects) or comparison group (36 participants;
      participants were matched with the experimental group by grade and sex).
      Participants in the experimental group received eight 2-h sessions of
      assertiveness training once a week. Data were collected before and after training
      and again one month after the end of the training using the Rotter's Internal
      versus External Control of Reinforcement Scale, Sex Role Inventory, Assertive
      Scale, Esteem Scale, and Interpersonal Communication Satisfaction Inventory. The
      generalized estimated equation (GEE) method was used for statistical analysis.
      The assertiveness and self-esteem of the experimental group were significantly
      improved in nursing and medical students after assertiveness training, although
      interpersonal communication satisfaction of the experimental group was not
      significantly improved after the training program.

PMID- 15519450
TI  - Environmental applications for biosurfactants.
AB  - Biosurfactants are surfactants that are produced extracellularly or as part of
      the cell membrane by bacteria, yeasts and fungi. Examples include Pseudomonas
      aeruginosa which produces rhamnolipids, Candida (formerly Torulopsis) bombicola,
      one of the few yeasts to produce biosurfactants, which produces high yields of
      sophorolipids from vegetable oils and sugars and Bacillus subtilis which produces
      a lipopeptide called surfactin. This review includes environmental applications
      of these biosurfactants for soil and water treatment. Biosurfactant applications
      in the environmental industries are promising due to their biodegradability, low
      toxicity and effectiveness in enhancing biodegradation and solubilization of low
      solubility compounds. However, more information is needed to be able to predict
      and model their behaviour. Full scale tests will be required. The role of
      biosurfactants in natural attenuation processes has not been determined. Very
      little information is available concerning the influence of soil components on
      the remediation process with biosurfactants. As most of the research until now
      has been performed with rhamnolipids, other biosurfactants need to be
      investigated as they may have more promising properties.

PMID- 15519451
TI  - Establishing principal soil quality parameters influencing earthworms in urban
      soils using bioassays.
AB  - Potential contamination at ex-industrial sites means that, prior to change of
      use, it will be necessary to quantify the extent of risks to potential receptors.
      To assess ecological hazards, it is often suggested to use biological assessment
      to augment chemical analyses. Here we investigate the potential of a commonly
      recommended bioassay, the earthworm reproduction test, to assess the status of
      urban contaminated soils. Sample points at all study sites had contaminant
      concentrations above the Dutch soil criteria Target Values. In some cases, the
      relevant Intervention Values were exceeded. Earthworm survival at most points was
      high, but reproduction differed significantly in soil from separate patches on
      the same site. When the interrelationships between soil parameters and
      reproduction were studied, it was not possible to create a good model of site
      soil toxicity based on single or even multiple chemical measurements of the
      soils. We thus conclude that chemical analysis alone is not sufficient to
      characterize soil quality and confirms the value of biological assays for risk
      assessment of potentially contaminated soils.

PMID- 15519452
TI  - The use of the barbell cluster ANOVA design for the assessment of environmental
      pollution: a case study, Wigierski National Park, NE Poland.
AB  - This report presents an assessment of chemical variability in natural ecosystems
      of Wigierski National Park (NE Poland) derived from the calculation of
      geochemical baselines using a barbell cluster ANOVA design. This method enabled
      us to obtain statistically valid information with a minimum number of samples
      collected. Results of summary statistics are presented for elemental
      concentrations in the soil horizons-O (Ol + Ofh), -A and -B, 1- and 2-year old
      Pinus sylvestris L. (Scots pine) needles, pine bark and Hypogymnia physodes (L.)
      Nyl. (lichen) thalli, as well as pH and TOC. The scope of this study also
      encompassed S and C stable isotope determinations and SEM examinations on Scots
      pine needles. The variability for S and trace metals in soils and plant
      bioindicators is primarily governed by parent material lithology and to a lesser
      extent by anthropogenic factors. This fact enabled us to study concentrations
      that are close to regional background levels.

PMID- 15519453
TI  - Recycling EDTA solutions used to remediate metal-polluted soils.
AB  - The objective of this research was to investigate the recycling of
      ethylenediamine-tetraacetic acid (EDTA) used for the removal of trace metals from
      contaminated soils. We successfully used Na2S combined with Ca(OH)2 to
      precipitate the trace metals allowing us to recycle the EDTA. The results of
      batch and column leaching experiments show that both Ca-EDTA and Na-EDTA are
      powerful chelating agents with a similar soil remediation potential. The major
      advantage of Ca-EDTA is the preservation of soil organic matter. We found that
      Na2S was capable of separating the metals Cd, Cu and Pb from EDTA; however, the
      precipitation of Zn required the addition of Ca(OH)2. After reusing the reclaimed
      EDTA seven times, over a 14-day period, EDTA reagent losses ranged from 19.5% to
      23.5%. Successive washing cycles enhanced the removal of trace metals from
      contaminated soils. The metal sulfide precipitates contain high concentrations of
      metals and could potentially be recycled.

PMID- 15519454
TI  - Zn, Cd and Pb accumulation and arbuscular mycorrhizal colonisation of pennycress
      Thlaspi praecox Wulf. (Brassicaceae) from the vicinity of a lead mine and smelter
      in Slovenia.
AB  - Significant hyperaccumulation of Zn, Cd and Pb in field samples of Thlaspi
      praecox Wulf. collected from a heavy metal polluted area in Slovenia was found,
      with maximal shoot concentrations of 14,590 mg kg(-1) Zn, 5960 mg kg(-1) Cd and
      3500 mg kg(-1) Pb. Shoot/root ratios of 9.6 for Zn and 5.6 for Cd show that the
      metals were preferentially transported to the shoots. Shoot bioaccumulation
      factors exceeded total soil Cd levels 75-fold and total soil Zn levels 20-fold,
      further supporting the hyperaccumulation of Cd and Zn. Eighty percent of Pb was
      retained in roots, thus indicating exclusion as a tolerance strategy for Pb. Low
      level colonisation with arbuscular mycorrhizal fungi (AMF) of a Paris type was
      observed at the polluted site, whereas at the non-polluted site Arum type
      colonisation was more common. To our knowledge this is the first report of Cd
      hyperaccumulation and AMF colonisation in metal hyperaccumulating T. praecox.

PMID- 15519455
TI  - Effects of golf course construction and operation on water chemistry of headwater
      streams on the Precambrian Shield.
AB  - To investigate the effects of golf course construction and operation on the water
      chemistry of Shield streams, we compared the water chemistry in streams draining
      golf courses under construction (2) and in operation (5) to streams in forested
      reference locations and to upstream sites where available. Streams were more
      alkaline and higher in base cation and nitrate concentrations downstream of
      operational golf courses. Levels of these parameters and total phosphorus
      increased over time in several streams during golf course construction through to
      operation. There was evidence of inputs of mercury to streams on two of the
      operational courses. Nutrient (phosphorus and nitrogen) concentrations were
      significantly related to the area of unmanaged vegetation in a 30 x 30 m area on
      either side of the sampling sites, and to River Bank Quality Index scores,
      suggesting that maintaining vegetated buffers along the stream on golf courses
      will reduce in-stream nutrient concentrations.

PMID- 15519456
TI  - Priority volatile organic compounds in surface waters of the southern North Sea.
AB  - The occurrence of 25 volatile organic compounds (VOCs) was studied from April
      1998 to October 2000 in the southern North Sea. Target VOCs were selected from
      lists of priority pollutants for the marine environment and included, e.g.,
      chlorinated short-chain hydrocarbons (CHCs), monocyclic aromatic hydrocarbons
      (MAHs), and chlorinated monocyclic aromatic hydrocarbons (CMAHs). Water samples
      were taken from the Channel, the Belgian Continental Shelf, the mouth of the
      Scheldt estuary and the Southern Bight, and were analysed by purge-and-trap and
      high-resolution gas chromatography-mass spectrometry. All data were produced by
      analyses deemed 'in control' by a rigorous quality assurance/quality control
      program provided by QUASIMEME (Quality Assurance of Information for Marine
      Environmental Monitoring in Europe). Chloroform and trichloroethene were commonly
      detected at concentrations up to 1900 and 270 ng l(-1), respectively. The other
      CHCs were generally found below 5 ng l(-1), and rarely exceeded 10 ng l(-1).
      Concentrations of MAHs were at least one order of magnitude higher than those of
      the CHCs. The higher levels were attributed to anthropogenic emissions from oil
      related activities in coastal areas. CMAHs, except chlorobenzene and 1,4
      dichlorobenzene, were hardly detected in North Sea waters. The levels of several
      CHCs and MAHs were shown to decrease compared to previous investigations in 1994
      1995, probably as a result of on-going emission reduction efforts. The occurrence
      of 1,1,1-trichloroethane, for instance, was substantially reduced since the
      Montreal Protocol was implemented in 1995.

PMID- 15519458
TI  - Effects of some environmental parameters on catalase activity measured in the
      mussel (Mytilus galloprovincialis) exposed to lindane.
AB  - Mussels (Mytilus galloprovincialis), collected from the Bizerta lagoon, were
      acclimated for four days to various conditions of temperature, salinity,
      photoperiod and food supply and then exposed to lindane at a concentration of 40
      microg l(-1). Catalase activity, which is a biomarker of exposure to an oxidative
      stress, was measured in the whole soft tissues of control and assay groups. In
      control mussels, high temperature, high salinity and light duration significantly
      increased catalase activity whereas this activity decreased when food, composed
      of freeze-dried, algae was available. When mussels were treated with lindane,
      catalase activities were higher than in controls. This increase was significant
      with temperature, salinity and light duration. The food supply did not change
      catalase activity, which was always higher compared to controls. Oxidative stress
      was shown in mussels exposed to lindane. The results highlight the need of
      considering abiotic parameters in biomonitoring studies, and especially when
      using catalase as a biomarker.

PMID- 15519457
TI  - Influence of temperature and salinity on heavy metal uptake by submersed plants.
AB  - Submersed plants can be useful in reducing heavy metal concentrations in
      stormwater, since they can accumulate large amounts of heavy metals in their
      shoots. To investigate the effects of water temperature and salinity on the metal
      uptake of two submersed plant species, Elodea canadensis (Michx.) and Potamogeton
      natans (L.), these plants were grown in the presence of Cu, Zn, Cd, and Pb at 5,
      11, and 20 degrees C in combination with salinities of 0, 0.5, and 5 per
      thousand. The metal concentrations in the plant tissue increased with increasing
      temperature in both species; the exception was the concentration of Pb in Elodea,
      which increased with decreasing salinity. Metal concentrations at high
      temperature or low salinity were up to twice those found at low temperature or
      high salinity. Plant biomass affected the metal uptake, with low biomass plants
      having higher metal concentrations than did high biomass plants.

PMID- 15519459
TI  - Polycyclic aromatic hydrocarbons storage by Fusarium solani in intracellular
      lipid vesicles.
AB  - Accumulation and elimination of polycyclic aromatic hydrocarbons (PAHs) were
      studied in the fungus Fusarium solani. When the fungus was grown on a synthetic
      medium containing benzo[a]pyrene, hyphae of F. solani contained numerous lipid
      vesicles which could be stained by the lipid-specific dyes: Sudan III and
      Rhodamine B. The fluorescence produced by Rhodamine B and PAH benzo[a]pyrene were
      at the same locations in the fungal hyphae, indicating that F. solani stored PAH
      in pre-existing lipid vesicles. A passive temperature-independent process is
      involved in the benzo[a]pyrene uptake and storage. Sodium azide, a cytochrome c
      oxidation inhibitor, and the two cytoskeleton inhibitors colchicine and
      cytochalasin did not prevent the transport and accumulation of PAH in lipid
      vesicles of F. solani hyphae. F. solani degraded a large range of PAHs at
      different rates. PAH intracellular storage in lipid vesicles was not necessarily
      accompanied by degradation and was common to numerous other fungi.

PMID- 15519460
TI  - Pinus nigra and Pinus pinaster needles as passive samplers of polycyclic aromatic
      hydrocarbons.
AB  - Nine polycyclic aromatic hydrocarbons (PAHs) were analysed in pine needles of
      different ages (from 6 to 30 months) collected from two species, Pinus nigra and
      Pinus pinaster, in seven sites located along a transect from a suburban to a
      rural area of Genoa (Italy). In all sites and for both species, concentrations of
      more volatile PAHs (phenanthrene, anthracene, fluoranthene, pyrene) were higher
      than those for other less volatile PAHs, which are preferentially sorbed to
      airborne particulates (benzo[a]anthracene, chrysene, benzofluoranthenes,
      benzo[a]pyrene). Concentrations of total PAHs found in P. nigra in the rural
      sites were, on the average, 2.3 times higher than those in P. pinaster growing
      nearby. In both pine species, concentrations of volatile PAHs increased according
      to needle age. Annual trends of other PAHs were more variable, with a general
      decrease in older needles. P. pinaster needles are shown to be more reliable
      passive samplers, since they are more resistant to plant diseases, and
      considerable variation in PAH concentration was observed in P. nigra needles with
      moulds and fungi.

PMID- 15519461
TI  - UV-absorbing compounds in subarctic herbarium bryophytes.
AB  - The UV-B-absorbing compounds of herbarium specimens of 10 subarctic bryophyte
      species collected during the years 1926-1996 and available at the Botanical
      Museum, University of Oulu, were studied. We studied whether herbarium specimens
      reflect changes in the past radiation climate through their methanol-extractable
      compounds. The order of gametophytes based on the average amount of total
      compounds (sum of A280-320 nm) per mass from the lowest to the highest was
      Polytrichum commune, Pleurozium schreberi, Hylocomium splendens, Sphagnum
      angustifolium, Dicranum scoparium, Funaria hygrometrica, Sphagnum fuscum,
      Sphagnum warnstorfii, Sphagnum capillifolium and Polytrichastrum alpinum, and the
      amount of UV-B-absorbing compounds per specific surface area correlated with the
      summertime daily global radiation and latitude. P. alpinum, F. hygrometrica and
      three Sphagnum species seem to be good indicators for further studies. The amount
      of UV-B-absorbing compounds revealed no significant trends from the 1920s till
      the 1990s, with the exception of S. capillifolium, which showed a significant
      decreasing trend.

PMID- 15519462
TI  - Environmental specimen bank samples of Pleurozium schreberi and Hylocomium
      splendens as indicators of the radiation environment at the surface.
AB  - Pleurozium schreberi (Brid.) Mitt. and Hylocomium splendens (Hedw.) Schimp.
      samples from the Finnish Environmental Specimen Bank were used to study the UV-B
      absorbing compounds as potential screens of the past radiation environment. The
      first series from southern and central Finland consisted of samples collected
      from 18 P. schreberi or H. splendens dominated sites in 1985 and 1995. The second
      series from four H. splendens dominated sites (two in southern and two in
      northern Finland) and two P. schreberi dominated sites (one southern and one
      northern) were from the years 1985, 1990, 1995 and 2000. In the first series, the
      moss surface area of the analyzed specimens (5 +/- 0.2 mg DW) was smaller in 1995
      (40% of both species collected in June) than in 1985 (40% of P. schreberi and 55%
      of H. splendens collected in September). The methanol-extractable UV-B-absorbing
      compounds of P. schreberi in 1985 and 1995 measured as absorbance at 10 nm
      intervals at 280-360 nm per mg DW revealed a negative correlation with
      reconstructed UV-radiation data. In the second series, the UV-B-absorbing
      compounds per specific surface area (surface area mm2 per DW) showed significant
      differences between the years. The highest values in both species were obtained
      in 1990. In H. splendens, a difference between the southern and northern samples
      was observed. The preliminary study encouraged the use of environmental specimen
      bank samples to indicate changes in surface radiation conditions.

PMID- 15519463
TI  - Uptake of radionuclides by vegetation at a High Arctic location.
AB  - Radionuclide levels in vegetation from a High Arctic location were studied and
      compared to in situ soil concentrations. Levels of the anthropogenic radionuclide
      137Cs and the natural radionuclides 40K, 238U, 226Ra and 232Th are discussed and
      transfer factor (TF) values and aggregated transfer (Tag) values are calculated
      for vascular plants. Levels of 137Cs in vegetation generally followed the order
      mosses > lichen > vascular plants. The uptake of 137Cs in vascular plants showed
      an inverse relationship with the uptake of 40K, with 137Cs TF and Tag values
      generally higher than 40K TF and Tag values. 40K activity concentrations in all
      vegetation showed little correlation to associated soil concentrations, while the
      uptake of 238U, 226Ra and 232Th by vascular and non-vascular plants was generally
      low.

PMID- 15519464
TI  - The significance of water ionic strength on aluminium toxicity in brown trout
      (Salmo trutta L.).
AB  - The toxicity of aluminium to fish is related to interactions between aluminium
      and the gill surface. We investigated the possible effect of water ionic strength
      on this interaction. The mortality of brown trout (Salmo trutta L.) exposed to
      three different degrees of Al polymerisation was compared in water with increased
      ionic strength (mean 7.31 x 10(-4) M) after additions of the base cations Ca2+,
      Mg2+, Na+ or K+, and in water with no such addition (mean ionic strength 5.58 x
      10(-4) M). Only a very slight ameliorating effect of increased ionic strength was
      observed, while the degree of Al polymerisation was of major importance in fish
      mortality. In addition, it was observed that smaller fish survived the Al
      exposures for a longer time than larger fish. We hypothesise that this is because
      larger fish are more susceptible to hypoxia than smaller fish.

PMID- 15519465
TI  - Age dependence of the accumulation of organochlorine pollutants in brown trout
      (Salmo trutta) from a remote high mountain lake (Redo, Pyrenees).
AB  - Polychlorobiphenyls (PCBs), hexachlorocyclohexanes (HCHs), hexachlorobenzene
      (HCB) and DDT were examined in the muscle of brown trout (Salmo trutta) from a
      high mountain lake located in the Pyrenees (Catalonia, Spain) that was used as a
      model of these lacustrine environments. Results indicate that fish age is the
      main factor of variability among specimens in this population that is subjected
      to atmospheric inputs of the organochlorine compounds (OC). Increases of 2- and
      20-fold between fish aged 1 year and 15 years old are found. The observed pattern
      cannot be explained in terms of fish size, condition factor, or muscle lipid
      content. Higher molecular weight compounds (higher lipophilicity) are better
      correlated with fish age than low molecular weight compounds. A transformation
      from 4,4'-DDT to 4,4'-DDE occurs in fish after ingestion; this results in
      amplified age-dependent signals, especially in male specimens. In contrast, PCB
      congener #180 has lower age dependence than the general OC group, which could be
      due to its high hydrophobicity (log K(ow) > 7). In any case, selective
      accumulation of hydrophobic compounds is already observed among younger fish
      (age, 1 year). Due to this effect, the relative OC composition does not reflect
      the main OC pollutants in the lake waters.

PMID- 15519466
TI  - Modelling the transport of suspended particulate matter by the Rhone River plume
      (France). Implications for pollutant dispersion.
AB  - A model to simulate the transport of suspended particulate matter by the Rhone
      River plume has been developed. The model solves the 3D hydrodynamic equations,
      including baroclinic terms and a 1-equation turbulence model, and the suspended
      matter equations including advection/diffusion of particles, settling and
      deposition. Four particle classes are considered simultaneously according to
      observations in the Rhone. Computed currents, salinity and particle distributions
      are, in general, in good agreement with observations or previous calculations.
      The model also provides sedimentation rates and the distribution of different
      particle classes over the sea bed. It has been found that high sedimentation
      rates close to the river mouth are due to coarse particles that sink rapidly.
      Computed sedimentation rates are also similar to those derived from observations.
      The model has been applied to simulate the transport of radionuclides by the
      plume, since suspended matter is the main vector for them. The radionuclide
      transport model, previously described and validated, includes exchanges of
      radionuclides between water, suspended matter and bottom sediment described in
      terms of kinetic rates. A new feature is the explicit inclusion of the dependence
      of kinetic rates upon salinity. The model has been applied to 137Cs and
      239,240Pu. Results are, in general, in good agreement with observations.

PMID- 15519467
TI  - A comparative study of cadmium phytoextraction by accumulator and weed species.
AB  - Phytoextraction has shown great potential as an alternative technique for the
      remediation of metal contaminated soils. The objective of this study was to
      investigate cadmium (Cd) phytoextraction ability of high biomass producing weeds
      in comparison to indicator plant species. The pot study conducted with 10 to 200
      mg Cd kg(-1) soil indicated that Ipomoea carnea was more effective in removing Cd
      from soil than Brassica juncea. Among the five species, B. juncea accumulated
      maximum Cd, but I. carnea followed by Dhatura innoxia and Phragmytes karka were
      the most suitable species for phytoextraction of cadmium from soil, if the whole
      plant or above ground biomass is harvested. In the relatively short time of this
      experiment, I. carnea produced more than 5 times more biomass in comparison to B.
      juncea. There were significant differences (p < 0.05) between the shoot length
      and shoot mass of control and treated plants.

PMID- 15519468
TI  - Heavy metal accumulation, heat shock protein expression and cytogenetic changes
      in Tetrix tenuicornis (L.) (Tetrigidae, Orthoptera) from polluted areas.
AB  - The orthopteran insect Tetrix tenuicornis, collected from polluted and unpolluted
      areas, was used to study heavy metal accumulation and its impact on stress
      protein levels and on changes in the number and morphology of chromosomes in
      mitotic and meiotic cells. During two consecutive years, insects were collected
      from polluted areas of zinc-lead mine spoils near Boleslaw (Poland) and from
      unpolluted areas near Busko and Staszow (Poland). T. tenuicornis from the
      polluted area showed 1.5, 4.03, 4.32 and 41.73 times higher concentrations of
      copper (Cu), zinc (Zn), lead (Pb) and cadmium (Cd), respectively, than insects of
      the same species collected from unpolluted areas. Insects exposed to heavy metals
      showed only small changes, and rather a decrease in the concentration of
      constitutive and inducible heat shock proteins Hsp70, the level of which
      increases under stress conditions. A cytogenetic study of T. tenuicornis revealed
      intra-population anomalies in chromosome number and morphology in mitotic and
      meiotic cells and the presence of an additional B chromosome in germinal cells.
      In 50% of females collected from polluted areas, mosaic oogonial mitotic
      chromosome sets and diploid, hypo- or hypertetraploid, tetraploid, and octoploid
      chromosome numbers were detected. In turn, 14.6% of males showed a heterozygous
      deficiency of chromatin in L2 and M3 bivalents in addition to the presence of B
      chromosomes.

PMID- 15519469
TI  - Study of PAH emission from the solid fuels combustion in residential furnaces.
AB  - The procedure for and results of a test study of polycyclic aromatic hydrocarbon
      (PAH) emission from a few types of solid fuels combustion in residential furnaces
      of various designs typical for Belarus are discussed. Greatest levels of PAH
      emission were detected from domestic wastes and wood waste combustion. Lowest
      levels of PAH emission are from peat briquette combustion. It was found that PAH
      concentration in off-gases from firewood combustion also varies significantly
      depending on the type of wood: the highest values of PAH are typical for waste
      gases from birch firewood combustion in comparison with pine firewood combustion.
      Draft PAH emission factors are proposed with intended application for emission
      inventory of such installations.

PMID- 15519470
TI  - Community-acquired pneumonia: new management strategies for evolving pathogens
      and antimicrobial susceptibilities.
AB  - Community-acquired pneumonia (CAP) is still one of the leading causes of
      mortality and morbidity. The most common bacterial cause of CAP is Streptococcus
      pneumoniae. The increase in antimicrobial resistance has raised concerns about
      the efficacy of available therapies, and a call for the reassessment of both
      existing and newer therapeutic agents. Although microbiological breakpoints are
      useful for monitoring the emergence of resistance, the current National Committee
      for Clinical Laboratory Standards (NCCLS) guidelines make no distinction between
      clinical and microbiological breakpoints. Recent changes in NCCLS breakpoints for
      extended spectrum cephalosporins have provided a more meaningful approach to
      susceptibility testing and to consideration of the site of infection. Further
      controversy surrounds the clinical guidelines relating to CAP in terms of which
      antimicrobial agents should be given empirically to which types of patients.
      Within this review, the role of monotherapy versus the need for combination
      antimicrobial therapy, which often includes a macrolide and an extended spectrum
      cephalosporin such as ceftriaxone, is discussed. This review also discusses the
      various aspects of antimicrobial susceptibilities of S. pneumoniae, the drivers
      and influences of increasing resistance, the clinical relevance of this
      resistance and possible therapeutic options in the face of changing
      susceptibilities and mixed bacterial aetiologies. New guidelines from the IDSA
      attempt to embrace these changes.

PMID- 15519471
TI  - Cyclic dipeptides exhibit synergistic, broad spectrum antimicrobial effects and
      have anti-mutagenic properties.
AB  - Cyclic dipeptides are known to have antiviral, antibiotic and antitumour
      properties. The aim of this study was to determine the combined effects of
      cyclo(L-leucyl-L-prolyl) and cyclo(L-phenylalanyl-L-prolyl) on the growth of
      vancomycin-resistant enterococci (VRE) and pathogenic yeasts, as well as
      determining their anti-mutagenic effects. This drug combination was especially
      effective against five VRE strains: Enterococcus faecium (K-99-38), E. faecalis
      (K-99-17), E. faecalis (K-99-258), E. faecium (K-01-312) and E. faecalis (K-01
      511) with MIC values of 0.25-1 mg/l. It was also effective against Escherichia
      coli, Staphylococcus aureus, Micrococcus luteus, Candida albicans and
      Cryptococcus neoformans with MIC values of 0.25-0.5 mg/l. In addition, the cyclic
      dipeptides exerted anti-mutagenic activity against Salmonella typhimurium TA98
      and TA100 strains in a Salmonella mutation assay. The number of mutant colonies
      of S. typhimurium strains TA98 and TA100 induced by exposure to AF-2 (0.2
      microg/plate) decreased in a concentration-dependent manner in the presence of
      the two cyclic dipeptides (correlation 0.72 and 0.78, respectively). Here, for
      the first time, we report synergistic effects of the cyclic dipeptides [cyclo(L
      leu-L-pro) and cyclo(L-phe-L-pro)] in inhibiting the growth of pathogenic
      microorganisms, as well as their anti-mutagenic effects in Salmonella strains.

PMID- 15519472
TI  - The importance of active efflux systems in the quinolone resistance of clinical
      isolates of Salmonella spp.
AB  - The aim of this study was to determine the importance of the active elimination
      of antibiotics by active efflux systems, in the decrease in fluoroquinolone
      sensitivity of clinical isolates of Salmonella spp. as well as the intrinsic
      antibiotic activity of certain active efflux system inhibitors. The effect of the
      active efflux system on the decrease in sensitivity to nalidixic acid,
      ciprofloxacin, ofloxacin and sparfloxacin was studied by investigating the
      variation in the in vitro activity of these compounds when assayed in association
      with reserpine and MC 207.110. The active efflux systems inhibited by reserpine
      displayed low activity in the elimination of these compounds, whereas those
      inhibited by MC 207.110 showed high activity in the elimination of nalidixic acid
      and sparfloxacin, but were less effective in the elimination of ofloxacin and
      ciprofloxacin. These two compounds did not exhibit intrinsic inhibitory activity
      against Salmonella spp. at the concentrations assayed. These mechanisms of
      resistance to antibiotics are complex and vary depending on the chemical
      composition of the antibiotics used, and perhaps the inhibitors of these systems,
      although they do not exhibit any intrinsic antibiotic activity, may be used as
      adjuvants to increase the activity of certain antibiotics. These mechanisms
      complement the mutations in the gyrA gene and this supports the thesis that it is
      necessary to lower the breakpoint established by the NCCLS for ciprofloxacin,
      since the strains studied have resistance mechanisms that reduce the activity of
      this drug and may favour the emergence of resistant mutants during treatment.

PMID- 15519473
TI  - High levels of dual resistance to clarithromycin and metronidazole and in vitro
      activity of levofloxacin against Helicobacter pylori isolates from patients after
      failure of therapy.
AB  - Current treatment for Helicobacter pylori infections generally includes two or
      more antimicrobials (amoxicillin, clarithromycin, nitroimidazoles, tetracycline,
      etc.), but treatment fails in 10-20% of all cases, often because of drug
      resistance. Levofloxacin has been proposed as an alternative for these refractory
      infections. We examined 67 H. pylori isolates from patients unsuccessfully
      treated with amoxicillin, clarithromycin, metronidazole and levofloxacin. Minimum
      inhibitory concentrations determined with the epsilometer test revealed
      clarithromycin and metronidazole resistance in 91 and 82.1% of the isolates,
      respectively; 52 (77.6%) were resistant to both drugs. All 67 isolates were
      susceptible to amoxicillin and tetracycline. Fifty-two isolates had levofloxacin
      MICs of 0.01-2 mg/l; the remaining 15 (22.4%), all clarithromycin- and
      metronidazole-resistant, had MICs >/= 8 mg/l. Levofloxacin may be an option for
      refractory H. pylori infections, but the choice should be based on in vitro
      susceptibility data, and physicians should consider local resistance patterns
      when treating these infections empirically.

PMID- 15519474
TI  - Characterisation of viridans group streptococci with different levels of Tet(M)
      mediated tetracycline resistance.
AB  - Streptococcus oralis 264-3, Streptococcus mitis 254-1 and S. mitis 264-1,
      isolated from the oral cavities of two children were each found to carry the
      tet(M) gene but exhibited different degrees of reduced susceptibility to
      tetracycline (tetracycline MICs of 2, 8 and 64 mg/L, respectively). The aim of
      this study was to determine the molecular basis for the different levels of
      tetracycline resistance (Tc(R)) observed. Escherichia coli HB101 carrying the
      cloned tet(M) genes exhibited similar levels of tetracycline susceptibility to
      those observed in the parental streptococcal strains (MICs of 1, 16, and 64 mg/L
      for tet(M) genes from S. oralis 264-3, S. mitis 254-1 and S. mitis 264-1,
      respectively). DNA sequencing revealed that S. oralis 264-3 had a tet(M) gene
      highly homologous to tet(M) carried by Tn916 from Enterococcus faecalis (99.6%
      identity), while the intermediate- and high-level Tc(R) strains had tet(M)
      sequences that resembled the tet(M) gene of Tn5251 from Streptococcus pneumoniae
      (99.3% and 99.4% identity, respectively). No differences were observed in the
      upstream attenuator structure for each of the strains and differences in reduced
      tetracycline susceptibilities could be attributed to changes in the deduced amino
      acid sequences of the Tet(M) proteins.

PMID- 15519475
TI  - Bactericidal activity of quinupristin-dalfopristin against strains of
      Staphylococcus aureus with the MLS(B) phenotype of resistance according to the
      erm gene type.
AB  - The bactericidal activity of quinupristin-dalfopristin was assessed by time-kill
      experiments against Staphylococcus aureus strains with characterized phenotypes
      and genotypes of MLS(B) resistance. A set of laboratory strains composed of
      isogenic pairs of S. aureus RN4220 derivatives containing or not the erm(A),
      erm(B) or erm(C) genes constitutively expressed and of 13 clinical isolates
      containing these genes inducibly or constitutively expressed were studied. Three
      of the clinical isolates with erm(B) or erm(A) genes had an unusual inducible
      MLS(B) cross resistance. The early bactericidal activity of quinupristin
      dalfopristin was altered against strains expressing constitutive quinupristin
      resistance regardless of the erm(A), erm(B) or erm(C) type of gene. We conclude
      that the bactericidal activity of quinupristin-dalfopristin against staphylococci
      was dependent on the activity of quinupristin rather than on the erm genotype of
      the strain.

PMID- 15519476
TI  - Screening of isolates from faeces for carbapenem-resistant Bacteroides strains;
      existence of strains with novel types of resistance mechanisms.
AB  - Isolates from faecal samples (n = 224) from the UK and Hungary were screened for
      carbapenem-resistant Bacteroides strains and were consecutively investigated for
      the resistance mechanisms through detection of cfiA genes, the presence or lack
      of insertion sequence insertions in their upstream regions and the production of
      carbapenemase activities. In this way, a significant number of strains (n = 7,
      3.1%) were recovered. They included 2 Bacteroides fragilis strains (one in each
      country) which harboured cfiA genes, but which were not activated by insertion
      sequence elements; this is reminiscent of some novel clinical B. fragilis
      strains. The cfiA-negative strains exhibited lower levels of carbapenem
      resistance and varying levels of carbapenemase activity, suggesting that other
      resistance mechanisms may also exist.

PMID- 15519478
TI  - Impact of antimicrobial exposure and beta-lactamase-producing bacteria on
      salivary beta-lactamase activity in infancy.
AB  - Beta-lactamase production by oral bacteria is common in infancy and is associated
      with use of antimicrobial agents in infants. The present longitudinal study aimed
      to examine the frequency of salivary beta-lactamase activity (SbetaA), to compare
      SbetaA with the presence of beta-lactamase-producing (beta+) aerobic and
      anaerobic species in saliva, and to estimate the impact of antimicrobial exposure
      on the emergence of SbetaA in healthy infants during their first year of life. At
      6 months, SbetaA was detected in 46% infants; 89% SbetaA-positive infants and 55%
      SbetaA-negative infants harboured beta+ species at this time (OR 7.08; CI 1.31
      38.34). At 12 months, SbetaA was detected in 54% infants. Exposure to
      antimicrobials during the first year of life increased the risk (OR 2.60; CI 0.72
      9.36) of having SbetaA.

PMID- 15519477
TI  - Significance of nested PCR and quantitative real time PCR for cytomegalovirus
      detection in renal transplant recipients.
AB  - Immunocompromised renal transplant recipients are susceptible to severe
      cytomegalovirus (CMV) infection that makes its detection important in clinical
      practice. A total of 536 blood and 536 serum samples from 67 renal transplant
      recipients who had previously been diagnosed with terminal renal insufficiency
      were studied for CMV infection. In all samples, serology, shell vial culture,
      antigenaemia and nested polymerase chain reaction (PCR) in blood and serum were
      tested, and a real-time quantitative PCR was run on 90 specimens. Sixty-seven
      blood donors were used as controls. The results show that the quantitative real
      time PCR assay could be of great interest for predicting CMV disease, and to
      monitor the onset of pre-emptive therapy.

PMID- 15519479
TI  - The effect of adsorption, filter material and point of dilution on antibiotic
      elimination by haemofiltration an in vitro study of levofloxacin.
AB  - We studied an in vitro model of continuous venous-venous haemofiltration (CVVH),
      into which levofloxacin 100 mg was infused, to determine levofloxacin adsorption
      and to determine the effect of filter material and point of dilution (pre- or
      post-filter) on sieving coefficient. Mean (standard deviation; S.D.) adsorption
      was 18.7 (5.3) mg for the polyamide filter and 40.2 (2.0) mg for the
      polyacrylonitrile (PAN) filter (P < 0.001). Post-dilution resulted in a minor,
      but statistically significant, decrease in sieving coefficient (pre-dilution 0.96
      (S.D. 0.10), post-dilution 0.88 (S.D. 0.11) with the PAN filter. These data
      indicate that the variability in published values for levofloxacin sieving
      coefficient are not due to variation in point of dilution or membrane type (PAN
      or polyamide). Significant adsorption of levofloxacin onto PAN filters occurs.

PMID- 15519480
TI  - Outpatient parenteral antibiotic therapy (OPAT) in different countries: a
      comparison.
AB  - In order to assess how outpatient parenteral antibiotic therapy (OPAT) is managed
      in different countries, we analyzed the data collected in the USA, UK and Italy
      by the International OPAT Registry using an ad hoc Access/Excel Microsoft
      program. The analysis of data concerned 9826 patients in the USA, 981 in the UK
      and 620 in Italy. Differences were observed in several aspects of OPAT management
      such as the infections treated and the antibiotics utilized. The duration of
      therapy also differed: it was much longer in Italy (56.0 average days), than in
      the USA (22.5 days) and UK (19.9 days). Delivery model, delivery route and
      infusion devices show substantial differences. The present analysis shows that
      OPAT is carried out with substantial differences in different countries probably
      according to different programmes and guidelines adopted.

PMID- 15519481
TI  - Pharmacodynamic target attainment analysis against Streptococcus pneumoniae using
      levofloxacin 500 mg, 750 mg and 1000 mg once daily in plasma (P) and epithelial
      lining fluid (ELF) of hospitalized patients with community acquired pneumonia
      (CAP).
AB  - The pharmacokinetics and pharmacodynamics of levofloxacin in patients with
      respiratory infections such as community-acquired pneumonia (CAP) are poorly
      documented. This work aimed at assessing the pharmacodynamic target attainment
      against Streptococcus pneumoniae using levofloxacin 500 mg, 750 mg and 1000 mg
      administered once daily in plasma (P) and epithelial lining fluid (ELF) of
      hospitalized patients with community acquired pneumonia. The pharmacokinetics of
      levofloxacin in elderly (>/=65 years) compared with younger patients (<65 years)
      hospitalized with CAP were simulated. Susceptibility data with S. pneumoniae from
      our ongoing national surveillance study (Canadian Respiratory Organism
      Susceptibility Study-CROSS) were then used to produce pharmacodynamic indices of
      AUC(0-24)/MIC(all.) Monte Carlo simulations were then used to analyse target
      attainment of levofloxacin using doses of 500 mg, 750 mg and 1000 mg once daily
      to achieve free drug AUC(0-24)/MIC(all) >/= 30-100 versus S. pneumoniae in
      patients with CAP. Pharmacokinetics of levofloxacin simulated after 500 mg, 750
      mg and 1000 mg once daily dosing resulted in levofloxacin volume of distribution:
      elderly patients = younger patients, while levofloxacin clearance was: elderly
      patients < younger patients. Levofloxacin t(1/2) values were longer in elderly
      patients (9.8 +/- 2.5h) than younger patients with CAP (7.4 +/- 2.5h). Free
      levofloxacin AUC(0-24) as well as AUC(0-24)/MIC(all) for S. pneumoniae were
      higher in elderly patients than younger patients. Monte Carlo simulation using
      levofloxacin 500 mg yielded probabilities of achieving free-drug AUC(0
      24)/MIC(all) of 30 in P and ELF (95.7% and 98.1%) in elderly and younger patients
      (72.7% and 80.6%) respectively. Levofloxacin 750 mg and 1000 mg once daily had
      probability of achieving free-drug AUC(0-24)/MIC(all) of 30 in P/ELF of
      98.1%/98.6% and 99.2%/99.0%, respectively, in elderly patients compared with
      89.9%/94.1% and 95.2%/96.5%, respectively, for younger patients. Probability of
      achieving of AUC(0-24)/MIC(all) of 100 in P or ELF was very low in both patient
      populations at different doses except in the case of elderly patients receiving
      levofloxacin in a dose of 1000 mg once daily P/ELF of 78.5%/87.0%. We conclude
      that levofloxacin pharmacokinetics in elderly patients with CAP are markedly
      different from those of younger patients. Levofloxacin 750 mg OD provides high
      probabilities of achieving free-drug AUC(0-24)/MIC(all) of 30 in both plasma and
      epithelial lining fluid in patients with CAP including younger patients.
      Levofloxacin 500 mg OD provides high probabilities of achieving free-drug AUC(0
      24)/MIC(all) of 30 in elderly patients with CAP, although we favour the 750 mg
      dosing in these patients as well. Levofloxacin 750 mg OD results in high
      probability of pharmacodynamic target attainment and improved bacteriological
      outcome against S. pneumoniae in patients with CAP.

PMID- 15519482
TI  - Severity scoring in community-acquired pneumonia caused by Streptococcus
      pneumoniae: a 5-year experience.
AB  - Multiple severity scoring systems have been devised and evaluated in community
      acquired pneumonia (CAP), but a simplified set of prognostic indicators has not
      yet been developed. Streptococcus pneumoniae is the most frequent aetiological
      agent of CAP. Our aim was to characterise the outcome in the light of different
      severity scoring systems and to compare the predictive values of different sets
      of clinical parameters, using available clinical data for pneumococcal CAP
      patients. This is a case series retrospective analysis that included consecutive
      adult pneumococcal CAP patients admitted to Danbury Hospital between 1 January
      1996 and 31 December 2000. The aetiology was confirmed by positive sputum and/or
      blood cultures. The severity assessment included the Pneumonia Outcome Research
      Trial (PORT) and British Thoracic Society (BTS) scoring systems and other
      additional parameters. Primary end-points were in-hospital CAP-attributable
      deaths and length of hospitalisation. N = 151 patients with S. pneumoniae CAP
      were identified. The mean (+/- standard deviation) age at the time of diagnosis
      was 68 (+/-15) years. Thirty-three patients (22%) were admitted to the medical
      intensive care unit. The mean (median) hospitalisation duration was 7.5 (+/-5)
      days. Door-to-antibiotic mean (median) administration time was 3.7 (2) hours.
      Most frequent antibiotics used initially were cephalosporins plus/minus
      macrolides or fluoroquinolones. The mean (+/- standard deviation) PORT score was
      105 (+/-37). The observed CAP-related mortality was 9/151 (5.9%, 95% confidence
      interval: 3-9%). The mortality rate in ICU was 18% (6/33). Sixty-nine patients
      (45%) had S. pneumoniae bacteraemia an admission. The bacteraemic and non
      bacteraemic patients had similar PORT scores (107 vs. 104, P = 0.66), length of
      hospitalisation (8 vs. 7 days, P = 0.41) and mortality rates (9% vs. 4%, P =
      0.30). In conclusion, patients admitted with pneumococcal CAP, although severe
      and with multiple co-morbidities had low in-hospital mortality rates and lengths
      of hospitalisation. Neither prior antimicrobial use (or failure) nor
      antimicrobial resistance contributed to an adverse outcome. S. pneumoniae
      bacteraemia failed to correlate with need for ICU, length of stay, higher
      morbidity index or fatal outcome. Low rates of empirical antibiotic use for non
      bacterial infections in the local community, implementation of an emergency
      department protocol for CAP therapy, early recognition of higher risk patients
      and placement in ICU, use of broad spectrum antibiotics, infectious disease
      approval or critical pathway restriction for admission orders, could all have
      combined to effect a good outcome for these patients.

PMID- 15519483
TI  - Taurolidine is effective in the treatment of central venous catheter-related
      bloodstream infections in cancer patients.
AB  - Taurolidine is an antimicrobial agent that was originally used in the local
      treatment of peritonitis and was shown to be effective in the prevention of
      catheter-related bloodstream infections (CR-BSI). In this pilot study, we used
      taurolidine solution as an intravenous (i.v.) lock into the totally implantable
      intravascular devices of 11 consecutive oncological patients with catheter
      related bloodstream infections not responding to systemic antimicrobial
      chemotherapy. All patients recovered completely from the infection. No adverse
      drug effects were seen. Three patients were successfully retreated for a
      recurrent infection. Our data suggest a beneficial role of taurolidine i.v. lock
      for the therapy of catheter-related bloodstream infections in oncological
      patients. Taurolidine i.v. lock application is feasible and could especially be
      useful in infections resistant to antibiotic chemotherapy.

PMID- 15519484
TI  - General and URTI-specific antibiotic prescription rates in a Malaysian primary
      care setting.
AB  - Antibiotic prescribing by primary care doctors has received renewed interest due
      to the continuing emergence of antibiotic resistance and the attendant cost to
      healthcare. We examined the antibiotic prescribing rate in relation to selected
      socio-demographic characteristics of the prescribers at the Seremban Health
      Clinic, a large public primary care clinic, designated for teaching, in the state
      of Negeri Sembilan, Malaysia. Data were obtained from: (1) retrospective review
      of prescriptions for the month of June 2002 and (2) a questionnaire survey of
      prescribers. A total of 10667 prescriptions were reviewed. The overall antibiotic
      prescribing rate was 15%; the rate (16%) was higher for the general Outpatient
      Department (OPD) than the 3% for the Maternal & Child Health Clinic (MCH). The
      antibiotic prescription rates for upper respiratory tract infection (URTI) were
      26% and 16%, respectively, for the OPD and MCH. Half of all the antibiotic
      prescriptions were for URTI making prescribing for URTI an appropriate target for
      educational intervention. The URTI-specific antibiotic prescription rate did not
      correlate with the prescribers' intention to specialise, patient load, perceived
      patient's expectation for an antibiotic, or the score for knowledge of
      streptococcal tonsillitis. Prescribing behaviours and record-keeping practices
      requiring correction were identified.

PMID- 15519485
TI  - Treatment of brucella spondylitis: lessons from an impossible meta-analysis and
      initial report of efficacy of a fluoroquinolone-containing regimen.
AB  - Although spondylitis is the most common of the complications of brucellosis, and
      is often debilitating and difficult to treat, there is no consensus on the
      preferred combination of antibiotics used. We attempted to perform a meta
      analysis based on series on brucellar spondylitis published in the last 22 years.
      Meta-analysis was aborted largely due to insufficient data recorded in most
      series. However, useful conclusions could be drawn, such as the importance of
      prolonged treatment, usually more than 12 weeks. No antibiotic combination was
      proven to be superior, but 14 different regimens were used in the series studied.
      The authors propose the use of a combination of doxycycline and ciprofloxacin for
      a period of 3 months, and report the successful use of such a combination in five
      patients with brucellosis and spondylitis.

PMID- 15519486
TI  - Prevalence of extended-spectrum beta-lactamase-producing Escherichia coli and
      Klebsiella pneumoniae in an urban hospital in Dhaka, Bangladesh.
AB  - The prevalence of extended-spectrum beta-lactamases (ESBL)-producing organisms in
      an urban hospital in Dhaka City was assessed over a 10-month period. A double
      disk test was performed to detect ESBL-producing Escherichia coli and Klebsiella
      pneumoniae. 43.2% and 39.5% of E. coli and K. pneumoniae had ESBL phenotypes,
      respectively. The combination of augmentin with ceftazidime detected the most
      ESBL-producing E. coli (39.5%) while augmentin with ceftriaxone was the best
      combination for the detection of ESBL (31.6%) in K. pneumoniae.

PMID- 15519487
TI  - Determination of avilamycin A and B in pig faeces by solid phase extraction and
      reverse-phase HPLC assay.
AB  - A HPLC method is described for the simultaneous determination of avilamycin A and
      B in pig faeces, following extraction using acetonitrile and normal-phase solid
      phase extraction. The HPLC stationary phase was Kromosil 5 micro C-18 with a
      mobile phase of 48% acetonitrile and 52% 0.01N ammonium acetate buffer, pumped at
      a flow rate of 1 ml/min. Detection was by UV absorbance at 295 nm and an
      injection volume of 50 microl was used. Recovery from faeces was >98% and intra
      assay precision (CV) was <9.0% for both compounds. The lowest limit of
      quantification was 0.9 mg/kg (avilamycin A) and 0.2 mg/kg (avilamycin B) with an
      accuracy of <15% error. No interference was seen from endogenous materials in pig
      faeces and commonly used veterinary antibiotics.

PMID- 15519488
TI  - Antimicrobial susceptibility profiles of Pseudomonas aeruginosa and
      Staphylococcus aureus isolated in Italy from patients with hospital-acquired
      infections.
AB  - Here we report the results of the Sentinel Project 2000 and give the
      susceptibility to selected antibiotics of 108 Pseudomonas aeruginosa and 108
      Staphylococcus aureus strains isolated from patients with hospital-acquired lower
      respiratory tract infections. In P. aeruginosa, susceptibility to aztreonam and
      ciprofloxacin was lower than 50%. The resistance rate to beta-lactams was up to
      25% and to amikacin 15.7%. Blood isolates showed 80-90% susceptibility to all
      antibiotics tested except for aztreonam and tobramycin. Overall, oxacillin
      resistance in S. aureus was 45%, reaching 64.3% among the bronchoalveolar lavage
      isolates, and 42.9% among the blood isolates. These worrying results confirm the
      need for continuous monitoring of bacterial resistance trends in the hospitals,
      mainly in ICUs.

PMID- 15519489
TI  - Piperacillin and gentamicin suppress Pseudomonas aeruginosa pyoderma acuta
      complicated by diabetes mellitus.

PMID- 15519490
TI  - Topoisomerases mutations and fluoroquinolone resistance in Stenotrophomonas
      maltophilia.

PMID- 15519491
TI  - Drug resistant patterns of enterococci recovered from patients in Tehran during
      2000-2003.

PMID- 15519492
TI  - MLS resistance genotypes in Group C and G streptococci.

PMID- 15519493
TI  - Susceptibility of Staphylococcus spp. to anti-infective agents during the past
      seven years.

PMID- 15519494
TI  - Methotrexate enhances prostaglandin D2-stimulated heat shock protein 27 induction
      in osteoblasts.
AB  - As for the pathogenesis of rheumatoid arthritis (RA), prostaglandins (PGs) act as
      important mediators of inflammation and joint destruction. Among them, PGD2 is
      well recognized as a potent regulator of osteoblastic functions. We previously
      showed that PGD2 stimulates the induction of heat shock protein 27 (HSP27) via
      protein kinase C (PKC)-dependent p38 mitogen-activated protein (MAP) kinase and
      p44/p42 MAP kinase in osteoblast-like MC3T3-E1 cells. Therefore, it is a current
      topic to clarify how HSP27 plays a role for regulating osteoblastic functions in
      the lesion of RA. On the other hand, methotrexate (MTX) is one of the most
      effective medicines for the treatment of RA. Here, we examined the effect of MTX
      on PGD2-stimulated HSP27 induction in MC3T3-E1 cells. The cells were pretreated
      with various doses of MTX including therapeutic dosage for RA, and then
      stimulated by PGD2. MTX significantly enhanced the PGD2- increased levels of
      HSP27 in a dose-dependent manner, although MTX alone had no effect on the levels
      of HSP27. In addition, MTX amplified the PGD2-increased levels of HSP27 mRNA. On
      the contrary, MTX had little effect on PGD2-induced formation of inositol
      phosphates, PKC activation and phosphorylations of MAP kinases. Our results
      strongly suggest that MTX enhances PGD2-stimulated HSP27 induction at a point
      downstream from MAP kinases in osteoblasts.

PMID- 15519495
TI  - Essential fatty acids in erythrocyte phospholipids during pregnancy and at
      delivery in mothers and their neonates: comparison with plasma phospholipids.
AB  - Evidence that the essential fatty acid (EFA) status during pregnancy and at birth
      may not be optimal is mainly based on fatty acid profiles of maternal and
      neonatal plasma phospholipids. However, erythrocyte phospholipids may be more
      reliable than plasma phospholipids to reflect the EFA status of an individual.
      Therefore, the present study compares the levels of EFA and of their derivatives
      (LCPUFA) in erythrocyte and plasma phospholipids collected during pregnancy and
      at delivery of 184 women and of their infants at birth. In general, the relative
      concentrations of erythrocyte and plasma phospholipid fatty acids (% of total
      fatty acids) were strongly correlated, but not at early pregnancy. The overall
      changes in fatty acid concentrations during pregnancy were qualitatively
      comparable between erythrocytes and plasma, although the comparability became
      less towards the end of pregnancy. The changes in absolute amounts (mg/l) of
      fatty acids in erythrocyte and plasma phospholipids also compare quite well till
      32 weeks of gestation, but not thereafter. Most maternal-neonatal differences in
      relative fatty acid concentrations are qualitatively comparable for erythrocyte
      and plasma phospholipids. However, significant differences were observed for the
      absolute amounts of arachidonic and docosahexaenoic acids. No matter these
      differences, plasma and erythrocyte phospholipids seem equally suitable to
      reliably quantify the more functional EFA and LCPUFA status based on fatty acid
      ratios. Correlations between neonatal and maternal fatty acid values at
      delivery/birth are highly significant in erythrocyte as well as plasma
      phospholipids. Neonatal erythrocyte (but not plasma) values also correlated
      strongly with maternal values at early pregnancy. Therefore, the neonatal EFA and
      LCPUFA status might be predicted on the basis of EFA and LCPUFA concentrations of
      maternal erythrocyte phospholipids at early pregnancy.

PMID- 15519496
TI  - Human bronchial smooth muscle cell proliferation via thromboxane A2 receptor.
AB  - Thromboxane A2 receptor (TP) mediates bronchial smooth muscle cell (BSMC)
      contraction, airway hyperresponsiveness, and airway inflammation in patients with
      asthma. In the present study, a pathogenic role of TP activation in airway
      remodeling was examined using primary cultures of human BSMC. A TP agonist, I
      BOP, concentration-dependently enhanced not only bromodeoxyuridine (BrdU) uptake
      but also cell proliferation of BSMC. A TP-selective antagonist, AA-2414, blocked
      the effects of I-BOP on both BrdU uptake and cell proliferation. I-BOP-induced
      BrdU uptake was significantly blocked by two non-selective tyrosine kinase
      inhibitors, genistein and herbimycin A, or a Src family tyrosine kinase
      inhibitor, PP2, but not by an inhibitor of epidermal growth factor (EGF) receptor
      associated tyrosine kinase, AG1478. In conclusion, TP receptor activation causes
      DNA synthesis and cell proliferation of human BSMC by activating tyrosine kinases
      including Src, but not by EGF receptor transactivation.

PMID- 15519497
TI  - Vitamin A deficiency reduces liver and colon docosahexaenoic acid levels in rats
      fed high linoleic and low alpha-linolenic acid diet.
AB  - Studies indicate that the transcription factor peroxisome proliferator-activated
      receptors (PPARs) regulate the activity of delta-6 and -5 desaturases and several
      key enzymes of peroxisomal beta-oxidation, including acyl-CoA oxidase. These
      enzymes are vital for the synthesis of docosahexaenoic (22:6 omega 3; DHA) and
      osbond (22:5 omega 6, OA) acids. An activated PPAR must form a hetrodimer with
      the obligate cofactor retinoid X receptor (RXR) to interact with a peroxisome
      proliferator responsive element (PPRE) of a target gene and to regulate
      transcriptional expression. The vitamin A metabolite, 9-cis retinoic acid, is the
      most potent ligand of RXR. We have tested the possibility that deficiency of
      vitamin A would compromise tissue levels of both DHA and OA in rats. Two groups
      of male Wistar rats were randomly distributed to receive vitamin A deficient
      (VAD) or sufficient (VAS) diet. After seven weeks of feeding, the rats were
      killed and colon and liver tissues removed for the analysis of fatty acids and
      antioxidant status. The VAD compared to the VAS rats had elevated levels of
      arachidonic (AA, P<0.001), adrenic acid (22:4 omega 6, P<0.005) and OA (P<0.0001)
      and reduced proportions of eicosapentaenoic (EPA, docosapentaenoic (DPA), DHA and
      total omega 3 fatty (P<0.0001) in colon choline phosphoglycerides (CPG).
      Similarly, liver CPG of the VAD rats had higher AA and adrenic acid and OA
      (P<0.0001), and lower EPA, DPA and DHA (P<0.0001) than the VAS rats. There was a
      similar fatty acid pattern in ethanolamine phosphoglycerides of the colon and
      liver tissues. These differences could not be explained by the conventional
      microsomal-peroxisomal pathway of the synthesis of the long-chain omega 6 and
      omega 3 polyunsaturated fatty acids. We postulate that deficiency of dietary
      vitamin A and the consequential depletion of retinoids inhibits DHA, and enhances
      OA, synthesis by differential effects on the independent synthetic pathways of
      the two fatty acids in the mitochondria. Various studies have documented that
      both DHA and vitamin A are vital for optimal visual and neural development and
      function. There is a need for further investigations to elucidate how vitamin A
      deficiency reduces membrane DHA level, and to delineate the synergistic effect of
      the two nutrients on vision, learning and memory.

PMID- 15519498
TI  - Effect of metformin vs. placebo treatment on serum fatty acids in non-diabetic
      obese insulin resistant individuals.
AB  - Metformin improves insulin sensitivity, which is correlated to phospholipid fatty
      acid composition in obese type 2 diabetics. We aimed at investigating the
      relationship between Metformin and fatty acids in obese insulin resistant non
      diabetic individuals. A double-blind, placebo-controlled 20-week trial was
      performed in 21 BMI and age-matched insulin resistant non-diabetic individuals
      receiving either Metformin or placebo. Insulin sensitivity together with
      metabolic parameters and fatty acids in serum phospholipids were measured at
      baseline and at 20 weeks. A significant decrease in body weight, BMI, percentage
      body fat, the sum of saturated fatty acids in serum phospholipids and increase in
      insulin sensitivity index were observed following the 20-week treatment. These
      changes did not differ significantly between the groups. Energy restriction
      rather than Metformin treatment appears to be responsible for the observed
      changes. The associations previously found in diabetics between insulin
      sensitivity and phospholipid fatty acids may not be mediated by Metformin.

PMID- 15519499
TI  - Prostaglandin E2 receptor subtype EP-2 is not involved in the induction of non
      pregnant guinea pig uterine contractions associated with terminal pregnancy.
AB  - Prostaglandin E2 (PGE2) exerts its biological effects through 4 different
      receptor subtypes, EP-1, EP-2, EP-3, and EP-4. Recently we have demonstrated the
      importance of the prostaglandin E2 receptor subtype EP-2 in the healing of bone
      defects and fractures. This discovery led to the identification of CP-533,536, an
      EP-2 selective agonist, a promising therapeutic alternative for the enhancement
      of bone healing and the treatment of fractures (J Bone Miner Res 18 (2003) 2033).
      PGE2 has a myriad of effects throughout the body including the induction of
      uterine contractions, which results in termination of pregnancies. Our objective
      in this study was to determine the role of the EP-2 receptor and specifically
      that of CP-533,536, an EP-2 specific agonist, to induce uterine contractions and
      terminate pregnancy in guinea pigs, an animal model of human pregnancy.
      Preliminary experiments confirmed earlier reports that the guinea pig uterus was
      more sensitive than that of the rat. The guinea pig uterus contains the four PGE2
      receptor subtypes, and ex vivo treatment of the uterus with PGE2 as expected
      causes profound uterine contractions. However, using receptor selective
      prostaglandin agonists including CP-533,536 we showed that the EP-1 and 3
      receptors not the EP-2 receptor is responsible for the induction of uterine
      contractions of PGE2. Further, CP-533,536 did not antagonize the ability of PGE2
      to induce uterine contractions in this model.

PMID- 15519500
TI  - No association between the PTGS2/PLA2G4A locus and schizophrenia in a Chinese
      population.
AB  - The present study was undertaken to replicate an association between the
      PTGS2/PLA2G4A locus and schizophrenia among a Chinese population. We recruited
      168 Chinese parent-offspring trios of Han descent, consisting of fathers, mothers
      and affected offspring with schizophrenia. Of 3 informative SNPs genotyped, no
      one showed allelic association with schizophrenia; the haplotype analysis also
      failed to capture a haplotypic association with the illness. Because the
      frequencies of alleles and genotypes of SNPs analyzed differ in the Chinese
      population as compared with a British population that initially showed the
      genetic association between the PTGS2/PLA2G4A locus and schizophrenia, the ethnic
      background may be a major reason for poor replication of the initial finding.

PMID- 15519501
TI  - Comments on Elevated urinary 8-isoprostaglandin F2 alpha in females with Graves'
      hyperthyroidism: K.M. Kim, K.-J. Paeng, J.R. Hahm, D.R. Kim, B.C. Chung.
      Prostagl. Leukotr. and Essent. Fatty Acids 71 (2004) 143-147.

PMID- 15519502
TI  - Urinary 8-isoprostoglandin F-2 alpha: a new marker in hyperthyroidism?

PMID- 15519503
TI  - Chemotherapy for advanced lung cancer.

PMID- 15519504
TI  - Intensity modulated radiation therapy.

PMID- 15519505
TI  - Best practice in assessing ototoxicity in children with cancer.

PMID- 15519506
TI  - Cutaneous malignant melanoma in Europe.
AB  - Cutaneous malignant melanoma is on the rise in fair skinned societies. Both its
      incidence and mortality rates have been increasing in Europe over the past
      decades, the latter seem to stabilise in Scandinavia. The main cause of melanoma
      is intermittent exposure to ultraviolet radiation, especially in combination with
      endogenous factors like skin type and genetic predisposition. Evidence on an
      association between sunbed use and melanoma is inconclusive, but seems to point
      to a slightly increased risk associated with sunbed use. Within Europe,
      considerably variation in patterns of melanoma incidence and mortality existed.
      In this paper, we discuss the possible explanations for the observed trends and
      options for primary and secondary prevention. Early detection seems the most
      promising way to combat the relatively poor survival rates in Southern and
      Eastern Europe.

PMID- 15519507
TI  - Perspectives in melanoma prevention: the case of sunbeds.
AB  - The incidence of cutaneous malignant melanoma (melanoma) and of basal cell
      carcinoma is still increasing in most fair-skinned populations. The fashion of
      intermittent exposure to solar ultraviolet (UV) radiations is considered the main
      cause of this increase. In 20 years time, tan acquisition through exposure to
      artificial sources of UV radiations has become frequent among fair-skinned
      adolescents and young adults. Modern sunbeds are powerful sources of UV
      radiations that do not exist in the nature, and repeated exposures to high doses
      of UVA constitute a new phenomenon in humans. A large prospective cohort study on
      106,379 Norwegian and Swedish women conducted between 1991 and 1999 has provided
      evidence for a significant, moderate increase in melanoma risk among regular
      sunbed users. Failure of past case-control studies to document with consistency
      the sunbed-melanoma association was probably due to a too short latency period
      between sunbed use and melanoma diagnosis, and to too few subjects with high
      total durations of sunbed use. Regulations of sunbed installation, operation and
      use should become standardised across the 25 European Union countries.
      Enforcement of regulations in tanning parlours remains inadequate. In contrast,
      the existence of regulations is presented by many tanning salon operators as a
      guarantee that sunbed use is safe. We stress the need for the control of
      information disseminated by the "tanning industry" on suppositions that sunbed
      use is safer than sun exposure, and on the hypothetical health benefits of
      tanning. New fluorescent UV lamps are proposed that have a spectrum similar to
      the midday sun. Given the known association between intermittent sun exposure and
      melanoma, public-health authorities should reconsider the soundness of the
      commercialisation of these lamps.

PMID- 15519508
TI  - Thalidomide in solid tumours: the resurrection of an old drug.
AB  - Following reports of its teratogenicity, thalidomide was banned from the market
      in the 1960s. Later, the elucidation that the inhibition of angiogenesis
      underlies this teratogenicity and the recognition of the importance of
      angiogenesis in malignancies has raised interest in thalidomide as an anti-tumour
      agent. Since then, numerous other mechanisms accounting for the anti-tumour
      effect of thalidomide have been revealed and many studies exploring the efficacy
      of thalidomide in tumours have been initiated. This Review focuses on the
      application of thalidomide and its derivatives in solid tumours, the mechanisms
      underlying their anti-tumour effects, and their potential to be applied in
      combination with other anti-tumour agents.

PMID- 15519509
TI  - Multistep laryngeal carcinogenesis helps our understanding of the field
      cancerisation phenomenon: a review.
AB  - In this paper, we try to briefly review the most recent knowledge on head and
      neck cancer, and especially multistep laryngeal carcinogenesis, and to simply
      explain how this has modified our understanding of field cancerisation
      phenomenon. Experimental studies, made possible by the recent evolution of
      microdissection systems, have demonstrated that the "spatial progression"of the
      histopathological phenotype in the surroundings of malignant or premalignant head
      and neck lesions correlates with molecular progression. Such a "spatial
      progression" can be hypothesised to reflect temporal progression. The field
      cancerisation process has been divided into three phases, each with its own
      histological and molecular characteristics. Each of these phases may have
      clinical implications: detection and monitoring of fields may help cancer
      prevention (molecular epidemiology), early detection of recurrence (or, more
      exactly, of second field tumours (SFTs)) (molecular diagnostics) and prognostic
      prediction after treatment. This model appears plausible, especially in
      explaining the development of multiple primary tumours (MPTs) in adjacent head
      and neck mucosal regions, with peculiar clinical and prognostic implications:
      These tumours can be defined as multiple field tumours (SFTs). However, the
      model, in our opinion, does not convincingly explain the development of second
      primary tumours (SPTs) at more distant sites, such as the lung, colon and
      prostate.

PMID- 15519510
TI  - Independent prognostic factors for distant metastases and survival in patients
      with primary uveal melanoma.
AB  - Adjuvant treatment strategies in uveal melanoma require determination of
      prognostic factors. Patients, who received primary therapy in 1994 and 1995 at
      our institution, were analysed. Of 271 patients 85% and 71% were available for
      follow up of 4 and 5 years. Forty three patients (15.9%) developed metastases.
      Kaplan-Meier analysis revealed a 5-year progression free survival (PFS) of 79%
      for the whole patient cohort. Extraocular tumor growth (EOG), ciliary body
      involvement or a largest tumor diameter (LTD) >14 mm were associated with a
      significantly lower 5-year PFS of 28%, 61.4% or 67.6%. In multivariate analysis
      time to progression was significantly associated with ciliary body involvement
      and LTD, and survival was associated with ciliary body involvement. Ciliary body
      involvement profoundly increased the risk for metastases (hazard ratio 6.9,
      P<0.001) within the first 3 years. This study determined patients with ciliary
      body involvement to be candidates for future adjuvant therapeutic interventions.

PMID- 15519511
TI  - Surgery and outcomes of ductal carcinoma in situ of the breast: a population
      based study in Australia.
AB  - We examined surgery and outcome in a population-based series of 2109 women newly
      diagnosed with ductal carcinoma in situ (DCIS) in 1995-2000 in New South Wales
      (NSW), Australia. The sole data source for the study was pathology records in the
      NSW Cancer Registry. Most DCIS was treated with breast-conserving surgery (BCS);
      use of breast conservation increased throughout the 6 years of the study. Women
      who were younger, had higher grade DCIS or had larger lesions were significantly
      and independently less likely to have BCS than other women. Eighteen percent of
      women had lymph nodes removed, most often with mastectomy. The NSW Cancer
      Registry does not collect information about radiotherapy. Based on cancer
      registrations alone, 97.7% of women were free of ipsilateral invasive cancer
      after three years; more women who had mastectomy were cancer-free (100%) than
      women who had breast-conserving surgery (97.2%; P=0.05).

PMID- 15519512
TI  - Same gain, less pain: potential patient preferences for adjuvant treatment in
      premenopausal women with early breast cancer.
AB  - The aim of this study was to determine the treatment preferences (adjuvant
      goserelin or cyclophosphamide, methotrexate and fluorouracil (CMF) chemotherapy)
      of healthy premenopausal women should they hypothetically develop oestrogen
      receptor (ER) positive early breast cancer. Two hundred pre or peri-menopausal
      women read two scenarios describing goserelin or chemotherapy. Information
      included: How and where treatments were administered, side-effects, their likely
      persistence and impact on fertility. Women stated their unprompted initial and
      final preferences with reasons for the choices made. Respondents showed an
      overwhelming preference for goserelin. 156 (78%) women favoured goserelin, 22
      (11%) chemotherapy and 22 (11%) remained undecided (P<0.0001). Primary reasons
      for preferring goserelin for were 105 (71%) avoidance of chemotherapy side
      effects, especially hair loss, perceived convenience and less disruption to
      normal life 54 (36%). The minority who preferred chemotherapy, valued the
      treatment finishing more quickly. These results together with clinical trial data
      showing equivalence of goserelin with CMF regimens suggest that premenopausal
      women with ER-positive tumours should at least be offered the choice of either
      adjuvant hormone therapy or chemotherapy.

PMID- 15519513
TI  - High conformality radiotherapy in Europe: thirty-one centres participating in the
      quality assurance programme of the EORTC prostate trial 22991.
AB  - Today, conformality in radiotherapy is at the centre of many investments in
      equipment and staffing. To estimate the current situation within the European
      Organisation for Research and Treatment of Cancer (EORTC) conformal radiotherapy
      trial for prostate cancer, a technology questionnaire was designed to assess
      whether participating centres can comply with the required radiotherapy
      procedures of EORTC trial 22991, where a high dose is prescribed to the prostate.
      Questions covered various items of computed tomography, data acquisition,
      treatment planning, delivery and verification. All centres (n=31) replied to the
      questionnaire. All generate beam's eye views and dose volume histograms. All, but
      two, centres use digitally reconstructed radiographs to display images. The vast
      majority of the centres perform at least weekly treatment verification and half
      have access to individual in vivo dosimetry. The results of the questionnaire
      indicate that participating centres have access to the equipment and apply the
      procedures that are essential for conformal prostate radiotherapy. The technology
      questionnaire is the first step in the extensive quality assurance programme
      dedicated to this high-tech radiotherapy trial.

PMID- 15519514
TI  - Thrombospondin-1 expression in relation to p53 status and VEGF expression in
      human breast cancers.
AB  - The aim of the present study was to study the expression and relationship of
      potential angiogenic factors. Paraffin-embedded tumour sections from 261 breast
      cancer patients were stained immunohistochemically for thrombospondin (TSP-1)
      expression. p53 status was previously determined by cDNA-based sequencing, and
      vascular endothelial growth factor (VEGF) protein expression had been previously
      analysed using an immunoassay. 241 cancers (92%) had detectable levels of TSP-1.
      No associations between TSP-1 and p53 status or VEGF were found. No correlations
      between TSP-1 and relapse-free (P=0.3), breast cancer-corrected (P=0.2) or
      overall survival (P=0.5) were found. A correlation was found for patients with
      p53 mutations, but negative p53 expression, with higher VEGF levels (P=0.009),
      but there was no correlation between this p53 group and those with low TSP-1
      levels (P=0.2). In conclusion, TSP-1 expression was not prognostic and was not
      associated with neither p53-status or VEGF expression.

PMID- 15519515
TI  - Oral vinorelbine given as monotherapy to advanced, elderly NSCLC patients: a
      multicentre phase II trial.
AB  - Vinorelbine intravenously (i.v.) demonstrated its efficacy and tolerability in
      advanced non-small cell lung cancer (NSCLC) patients, including elderly subjects.
      Since vinorelbine is now available as an oral formulation this phase II open
      study was designed to evaluate its activity and tolerability in advanced, elderly
      NSCLC patients. A total of 56 chemonaive patients were recruited from April 2001
      through to March 2002. The dosage schedule, already tested in younger NSCLC
      patients, was 60 mg/m(2)once a week for three weeks (first cycle), followed by 80
      mg/m(2) once a week until disease progression or development of unacceptable
      toxicity. A limited sampling scheme was used for performing pharmacokinetic
      analysis on 52 of 56 patients enrolled in the study. Treatment was well tolerated
      with grade 3/4 neutropenia in 11/17 patients (20/30%) and febrile neutropenia in
      1 (2%). Six partial responses (11%) and 25 stable disease responses were
      recorded, with a disease control rate of 55%. Median overall survival was 8.2
      months (95% Confidence Interval (CI) [6.2-11.3]). The clinical benefit response
      rate was 31% on 32 evaluable patients. Pharmacokinetic profiles appeared quite
      similar to the historical profiles recorded following i.v. administration. Oral
      vinorelbine appears to be a reasonable alternative to i.v. vinorelbine, both in
      terms of activity and tolerability, in advanced, elderly NSCLC patients.

PMID- 15519516
TI  - Gemcitabine, epirubicin and docetaxel as primary systemic therapy in patients
      with early breast cancer: results of a multicentre phase I/II study.
AB  - Developing primary systemic chemotherapy (PST) regimens that induce higher
      pathological complete response (pCR) rates remains a challenge in operable breast
      cancer. We recruited 77 eligible patients into a multicentre phase I/II study to
      evaluate the maximum tolerated dose (MTD), toxicity and efficacy of preoperative
      gemcitabine day 1 and 8 (800 mg/m(2) fixed dose), epirubicin and docetaxel on day
      1 (doses escalated from 60 mg/m(2)) (GEDoc), repeated 3-weekly for 6 cycles with
      filgrastim support. MTD for epirubicin was 90 mg/m(2) and for docetaxel 75
      mg/m(2). Dose-limiting toxicities (DLTs) included febrile neutropenia and grade 3
      diarrhoea. Clinical response rate was 92%, pCR rate was 26%. 79% of patients had
      breast-conserving surgery. Grade 3/4 leucopenia was the main toxicity, occurring
      in 55 (87%) of 63 patients treated at the MTD. Non-haematological toxicity caused
      no serious clinical problems. In conclusion, GEDoc is highly active as PST.
      Efficacy and toxicity compare favourably with other effective combinations.

PMID- 15519517
TI  - Development of a questionnaire module to supplement the EORTC QLQ-C30 to assess
      quality of life in patients with hepatocellular carcinoma, the EORTC QLQ-HCC18.
AB  - Measurement of quality of life (QoL) in hepatocellular carcinoma (HCC) requires
      assessment of factors related to chronic liver disease, as well as issues related
      to the primary tumour and its treatment. This study describes the development of
      a questionnaire module in patients from Europe, as well as Taiwan and Hong Kong.
      The questionnaire was developed according to the European Organisation for
      Research and Treatment of Cancer (EORTC) QoL Group guidelines. Twenty nine QoL
      issues were identified from a literature search. Semi-structured interviews with
      patients (n=32) and health-care professionals (n=10) reduced the issues to 22
      items forming a provisional questionnaire. This was tested in 158 patients from
      three countries. Descriptive statistics and clinical judgement reduced the module
      to 18 items conceptualised as containing six scales and two single item. This
      study recommends the EORTC QLQ-HCC18 to accompany the QLQ-C30 to measure QoL in
      clinical trials in HCC.

PMID- 15519518
TI  - Predicting cisplatin ototoxicity in children: the influence of age and the
      cumulative dose.
AB  - The aim of this study was to determine the risk factors for high-frequency
      hearing loss in children treated with cisplatin. We scored off-treatment pure
      tone audiograms from 153 children (age 6 months to 18 years) who had completed
      cisplatin therapy (40-200 mg/m(2)/cycle) for germ cell tumours, hepatoblastoma,
      neuroblastoma or osteosarcoma. The risk of developing bilateral moderate to
      severe high-frequency hearing loss was significantly related to the age at
      treatment (P<0.001), and individual and cumulative cisplatin dosages (both
      P<0.005). Logistic regression showed that children younger than 5 years were at a
      greater risk of sustaining cisplatin ototoxicity than children older than 15
      years, controlling for individual and cumulative doses of cisplatin (Odds Ratio
      (OR)=21.17, 95% Confidence Interval (CI): 2.48-180.94). Age at treatment and the
      cumulative dose of cisplatin were the two most important risk factors in
      predicting moderate to severe high-frequency hearing loss in children treated
      with cisplatin.

PMID- 15519519
TI  - Port-A-Cath infections in children with cancer.
AB  - Implanted subcutaneous (s.c.) central venous port accesses including Port-A-Cath
      (PAC) facilitate the administration of chemotherapy or blood products and are
      frequently used in children with cancer. The incidence of PAC-related infections
      was determined in 155 consecutive paediatric cancer patients with PAC followed
      for a total of 134,773 days (median, 738; range, 25-2080). Overall, 48
      bloodstream infections occurred in 26 patients. 12 (25%) of these infections and
      3 local infections at the insertion site were treatment-resistant and demanded
      removal of the PAC. Coagulase-negative staphylococci were involved in 12 of these
      15 episodes. The rate of clearly PAC-related infections in this so far largest
      reported series was 0.11 episodes per 1000 PAC days, one of the lowest in the
      literature. Although catheter-related infections demanded PAC removal in 8% of
      our patients, the long periods PAC were in use and their benefits argue for
      continued PAC use in the paediatric cancer population.

PMID- 15519520
TI  - Inherited cancer in children: practical/ethical problems and challenges.
AB  - Over recent years significant molecular advances have led to a better
      understanding of the genetics of both syndromic and non-syndromic paediatric
      cancers. In addition many hereditary cancer predisposition syndromes are now
      recognised, some of which have implications for children in affected families.
      Improvements in gene mutation screening will increase the sensitivity, accuracy
      and therefore the applicability of genetic testing in these conditions. This
      review will deal with four main areas pertaining to paediatric cancer genetics
      (i) genetic aspects of some non-syndromic paediatric cancers (ii) paediatric
      cancer predisposition syndromes, (iii) the management of children in families
      with predominantly adult- onset cancer predisposition syndromes and (iv) special
      ethical, legal, social and psychological considerations in the management of
      children, with actual or possible genetic cancer predisposition. Current concepts
      and controversies in the rapidly changing field of paediatric cancer genetics
      will be examined in detail and the application of existing guidelines and their
      limitations will be discussed.

PMID- 15519521
TI  - Genetics and childhood cancer. Commentary on: inherited cancer in children:
      practical/ethical problems and challenges.

PMID- 15519522
TI  - A gene-environment interaction between occupation and BRCA1/BRCA2 mutations in
      male breast cancer?
AB  - The association of male breast cancer (MBC) with a positive breast cancer (BC)
      family history and with BRCA1/2 germ-line mutations points to a genetic
      component; a relationship with occupation has also been reported. Recently, we
      identified pathogenetic BRCA1/2 mutations in a population-based series of Italian
      MBC patients: here in, we investigated interactions between a carrier status for
      BRCA1/2 mutations and occupation using a case-case design and estimating case
      only odds ratios (CORs). Truck-driving was the most frequent occupation (3/4 BRCA
      related cases and 2/19 unrelated cases). An interaction between carrier status
      and working as a truck-driver emerged, when we classified MBC cases as
      "ever/never-held" this job title (COR 25.5; 95% Confidence Limits (CL): 1.1
      1,412.5) or according to truck-driving as the "longest-held" work (COR 54.0; 95%
      CL: 1.6-2,997.5). The possible modifying effect on MBC risk in subjects carrying
      BRCA1/2 germ-line mutations of an occupation characterised by exposure to
      chemicals such as polycyclic aromatic hydrocarbons (PAH) that are capable of
      inducing DNA damage, may provide clues to the role of environmental exposures in
      modifying BC risk in mutation carriers in both genders.

PMID- 15519523
TI  - Familial association of colorectal adenocarcinoma with cancers at other sites.
AB  - Data on the familial associations of colorectal cancer (CRC) of adenocarcinoma
      histology are limited, but they are of interest because they may give us clues
      about as yet unknown family clusters. We calculated standardised incidence ratios
      (SIRs) for right- and left-sided colon cancer and rectal cancer in offspring
      using data from the Swedish Family-Cancer Database covering familial tumours from
      1991 to 2000. The offspring were at an increased risk of developing colon
      adenocarcinoma when parents presented with CRC (SIR 1.81), endometrial (SIR 1.52)
      and kidney (SIR 1.42) cancers. The SIRs in siblings were increased when a co
      sibling was diagnosed with CRC (SIR 3.26), myeloma (SIR 2.65) and leukaemia (SIR
      2.53). Right-sided colon cancer was associated with familial pancreatic, squamous
      cell skin cancers, thyroid gland cancer and Hodgkin's disease. Left-sided colon
      cancer was associated with testicular cancers. Rectal cancer was associated with
      cervical and genital cancers in mothers. Most of the findings were consistent
      with data on known cancer syndromes. A new association was noted where rectal
      cancer in offspring was related to cervical and female genital cancers in mothers
      through an unknown mechanism. Hodgkin's disease and myeloma were also associated
      with right-sided colon cancer in offspring. The association with carcinoma of the
      testis, renal parenchyma, skin and leukaemia need to be confirmed in an
      independent series.

PMID- 15519524
TI  - The impact of education and occupation on the employment status of cancer
      survivors.
AB  - We explored the effect of a diagnosis of cancer on employment according to cancer
      type, education, occupation, age, gender, mother tongue (Swedish or Finnish),
      calendar time and hospital district. All 12,542 new cancer cases diagnosed in
      1987-1988 and 1992-1993, aged 15-60 years at the time of the diagnosis were
      identified from the Finnish Cancer Registry. The employment rate of the cancer
      survivors 2-3 years after the diagnosis was only 9% lower than their gender- and
      age-matched referents. However, we found that education and occupation modified
      the effect of cancer on the employment; the difference between cancer survivors
      and their referents in the probability of being employed was greater in the lower
      than in the higher educational groups. A modifying effect of education on the
      probability of employment was found among people with cancer of the lung,
      stomach, rectum and cervix uteri and those with cancers of the nervous system.

PMID- 15519525
TI  - Hybrid analysis for up-to-date long-term survival rates in cancer registries with
      delayed recording of incident cases.
AB  - Up-to-date monitoring of long-term survival is an important task of population
      based and clinical cancer registries. A few years ago, a new method of survival
      analysis, denoted period analysis, was introduced to provide more up-to-date
      estimates of long-term survival. However, a prototypical period analysis may not
      be applicable in situations with delayed recording of incident cases. We
      introduce herein a hybrid type of analysis that combines elements of both
      traditional and period analyses which may still be feasible in such settings. The
      performance of the hybrid type of analysis compared with other design options is
      empirically evaluated and illustrated for children diagnosed with cancer in the
      United States. The empirical evaluation indicates that hybrid analysis may be
      useful to derive more up-to-date estimates of long-term survival compared with
      traditional design options if there is a strong improvement of survival over
      time, even in situations with a substantial delay in recording of incident cases.

PMID- 15519526
TI  - Epidemiological differences for cutaneous melanoma in a relatively dark-skinned
      Caucasian population with chronic sun exposure.
AB  - The aim of this study was to reveal differences in the epidemiology and to
      identify significant risk factors for cutaneous melanoma (CM) in a relatively
      dark-skinned, chronically sun-exposed Caucasian population. This group is
      considered to have a low risk for this tumour. One hundred and ten newly
      diagnosed patients with primary CM and 110 age- and gender-matched controls, all
      of Cretan origin, were interviewed and underwent a complete skin examination.
      Solar keratoses odds ratio (OR) 6.2 and lentigines (OR 2.2), common and atypical
      naevi (OR 5.4 and 3.0, respectively), blonde or red hair colour (OR 3.1), skin
      phototypes I/II (OR 1.8), as well as total sun exposure (weeks per year) (OR
      1.03), were all significantly associated with CM risk in a multivariate logistic
      regression analysis. In the relatively dark-skinned Cretan population, sun
      exposure indices represent the most important risk markers for CM which contrasts
      with data from fair-skinned Caucasian populations where melanocytic naevi are the
      main risk factors.

PMID- 15519527
TI  - Different signalling pathways regulate VEGF and IL-8 expression in breast cancer:
      implications for therapy.
AB  - Elevated expression of pro-angiogenic cytokines is associated with aggressive
      tumour growth and decreased survival of patients with breast cancer. In general,
      the breast cancer cell lines with high vascular endothelial growth factor (VEGF)
      expression also express high levels of interleukin-8 (IL-8). The consequence of
      inhibiting mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3
      kinase (PI3K), both implicated in regulation of these cytokines, was examined in
      four cell lines. Treatment with the mitogen-activated protein
      kinase/extracellular signal-related kinase (MEK) inhibitor U0126 reduced
      expression of VEGF and IL-8 in MDA-MB-231 cells, partially inhibited expression
      in MDA-MB-468 and Hs578T cells, with minimal effects in GI101A cells. Treatment
      with LY294002 reduced cytokine expression in GI101A and MDA-MB-468 cells, with
      partial reduction in Hs578T and less effect in MDA-MB-231 cells. Thus, IL-8 and
      VEGF were regulated by different signalling pathways in different cell lines;
      this suggests that inhibition of the dominantly active pathway can downregulate
      both angiogenic cytokines. Recognising which signalling pathway is active may
      identify targets for anti-angiogenic therapy of breast cancer.

PMID- 15519528
TI  - Somatic D-loop mitochondrial DNA mutations are frequent in uterine serous
      carcinoma.
AB  - The mitochondria plays a role in apoptosis. Its genome is also more susceptible
      to mutations because of high levels of reactive oxygen species and limited repair
      mechanisms. The D-loop of mitochondrial DNA (mtDNA) contains essential
      transcription and replication elements, and mutations in this region might alter
      the rate of DNA replication. We examined genetic alterations in the D-loop region
      of mtDNA in uterine serous carcinoma (USC) samples and their paired normal
      adjacent endometrium. DNA was extracted after laser-capture microdissection of
      paraffin-embedded tissues from eight patients with USC. The entire D-loop genome
      was amplified using nine pairs of overlapping primers. Denatured polymerase chain
      reaction (PCR) products were subjected to single-strand conformation polymorphism
      (SSCP) analysis. Somatic mtDNA alterations were detected in five tumours (63%).
      Our study indicates that mtDNA D-loop sequence alterations occur at a high
      frequency in USC suggesting that mtDNA mutations may play a role in the
      development of USC.

PMID- 15519529
TI  - Analysis of transcripts from 17p13.3 in medulloblastoma suggests ROX/MNT as a
      potential tumour suppressor gene.
AB  - Haploinsufficiency of the human 17p13.3 region is associated with 35% to 50% of
      medulloblastomas, indicating the presence of one or more tumour suppressor genes
      which have not yet been identified. Of 119 genes residing in this region, seven
      genes--14-3-3epsilon (YWHAE), HIC-1, ROX/MNT (a helix-loop-helix transcription
      factor and member of the MYC/MAX superfamily), KIAA0399, UBE2G1 (ubiquitin
      ligase), ALOX15, and MINK--encode proteins with potential links to cancer. We
      investigated these genes and found significant levels of expression of ROX/MNT in
      adult human cerebellum, and in embryonic and postnatal mouse cerebellum. Six of
      14 medulloblastomas showed a reduction of ROX/MNT expression, accompanied by a
      reduction of both UBE2G1 and 14-3-3epsilon in three tumours and a reduction of
      UBE2G1 in one tumour. Moreover, the relative expression of MYC to ROX/MNT was
      increased in 4 of the 14 medulloblastomas. Collectively, these data suggest that
      ROX/MNT should be considered a potential tumour suppressor gene in
      medulloblastoma.

PMID- 15519530
TI  - Dementia of Alzheimer's disease and other neurodegenerative disorders--memantine,
      a new hope.
AB  - Alzheimer's disease is the fourth largest cause of death for people over 65 years
      of age. Dementia of Alzheimer's type is the commonest form of dementia, the other
      two forms being vascular dementia and mixed dementia. At present, the therapy of
      Alzheimer's disease is aimed at improving both, cognitive and behavioural
      symptoms and thereby, quality of life for the patients. Since the discovery of
      Alzheimer's disease by Alois Alzheimer, many pathological mechanisms have been
      proposed which led to the testing of various new treatments. Until recently the
      available drugs for the treatment of Alzheimer's disease are cholinesterase
      inhibitors, which have limited success because these drugs improve cognitive
      functions only in mild dementia and cannot stop the process of neurodegeneration.
      Moreover, drugs of this category show gastrointestinal side effects. As the cells
      of central and peripheral nervous system cannot regenerate, newer strategies are
      aimed at preserving the surviving neurons by preventing their degeneration. NMDA
      receptor-mediated glutamate excitotoxicity plays a major role in Abeta-induced
      neuronal death. Hence, it was thought that NMDA receptors could be a promising
      target for preventing the progression of Alzheimer's disease. All the compounds
      synthesized initially in this category showed toxicity mainly because of their
      high affinity for NMDA receptors. Memantine (1-amino adamantane derivative), NMDA
      receptor antagonist was reported to be effective therapeutically in Alzheimer's
      disease. It was available in Germany as well as European Union and has been
      approved for moderate to severe dementia in United States of America recently. It
      is an uncompetitive, moderate affinity antagonist of NMDA receptors that inhibits
      the pathological functions of NMDA receptors while physiological processes in
      learning and memory are unaffected. Memantine is also reported to have beneficial
      effects in other CNS disorders viz., Parkinson's disease (PD), stroke, epilepsy,
      CNS trauma, amyotrophic lateral sclerosis (ALS), drug dependence and chronic
      pain. Mechanisms of neuroprotection, preclinical and clinical evidence for
      effectiveness of memantine have been provided. Pharmacology and pharmacokinetics
      of memantine and other NMDA-receptor antagonists in comparison with currently
      approved drugs for dementia treatment have been discussed. The focus is on
      'glutamate excitotoxicity' and glutamate receptors as drug target. Various other
      novel strategies for the treatment of dementia of neurodegenerative disorders
      have also been discussed.

PMID- 15519531
TI  - Cancer--an ayurvedic perspective.
AB  - An integrated approach is needed to manage cancer using the growing body of
      knowledge gained through scientific developments. Thousands of herbal and
      traditional compounds are being screened worldwide to validate their use as anti
      cancerous drugs. The science of Ayurveda is supposed to add a step on to the
      curative aspects of cancers that have resemblance with clinical entities of
      arbuda and granthi mentioned in Sushrutha samhita. Hence, an attempt is made in
      this review to discuss about the pathology and therapeutic management of various
      cancers described in Ayurveda. Review of literature on anticancer drugs of plant
      origin revealed identification of newer ayurvedic drugs that are not mentioned in
      the ancient texts. These new findings add up to ayurvedic science that has been
      developed through ages. In addition, details of experimental and clinical studies
      conducted on single and compound ayurvedic preparations for their anticancer
      efficacy strongly emphasize ayurvedic therapy as a scientifically driven one and
      not simply unconventional.

PMID- 15519532
TI  - Effect of atorvastatin on non-cholesterol sterols in patients with type 2
      diabetes mellitus and cardiovascular disease.
AB  - An increased risk of cardiovascular morbidity and mortality in diabetes mellitus
      type 2 has been associated with disturbances of lipid homeostasis. Recently,
      decreased intestinal absorption of cholesterol and increased liver cholesterol
      production have been reported. To investigate the influence of cholesterol
      lowering therapy using statin on cholesterol turnover in diabetes mellitus type
      2, the levels of non-cholesterol based sterols were studied. One hundred and
      thirty five patients with type 2 diabetes and non-diabetic controls with
      cardiovascular diseases were studied. Both groups were divided into two
      subgroups: treated with atorvastatin and without statin therapy. The diabetics
      showed significantly higher levels of lathosterol (6.97micromol l(-1) versus
      5.11micromol l(-1), p = 0.012) and lower levels of sitosterol (5.03micromol l(-1)
      versus 8.98micromol l(-1), p < 0.001) and campesterol (6.35micromol l(-1) versus
      9.80micromol l(-1), p < 0.001). Non-diabetics showed no significant differences
      in non-cholesterol based sterols in relation to atorvastatin therapy. A
      significantly lower level of lathosterol as well as a decrease in
      lathosterol/cholesterol ratio in the statin treated groups was found in diabetics
      (4.11micromol l(-1) versus 7.83micromol l(-1), p < 0.001). The results based on
      ANOVA analysis show that the effect of atorvastatin on the lathosterol level is
      more pronounced in diabetics. Regression analysis showed the relationship between
      increased triglycerides levels and the increase in cholesterol synthesis. The
      calculated regression model for loglathosterol in diabetics has the following
      form: log(lathosterol) = 2.76 - 0.52.statin + 0.22.cholesterol (ANOVA, p < 0.001,
      R(2) = 34%, p = 0.005 for statin, p < 0.001 for cholesterol). We conclude that in
      spite the total cholesterol level in diabetics type 2 is not increased, its
      endogenous synthesis is enhanced. Our results show that the diabetics type 2 with
      increased serum lathosterol and expressed metabolic syndrome (mild increase of
      triglycerides) might represent a suitable group for intensive treatment with
      statins.

PMID- 15519533
TI  - Hypovolaemia-induced vasodilatation during angiotensin AT1 receptor blockade:
      role of the AT2 receptor.
AB  - AT(1) receptor antagonists may interfere with the haemodynamic determinants of
      arterial pressure either directly or indirectly through the stimulation of AT(2)
      receptor provided Ang II is available to interact with them. In order to evaluate
      the counteracting haemodynamic effect of AT(2) receptor, a prospective,
      randomized, controlled experimental study was carried out in anaesthetised
      juvenile pigs. Pigs were randomly assigned to receive placebo (n = 6), valsartan,
      an AT(1) receptor antagonist (a-AT(1) group; n = 6), or valsartan and PD 123319,
      an AT(2) receptor antagonist (a-AT(1-2) group; n = 6) after anaesthesia and
      before hypovolaemia by 20% of the total estimated blood volume. Thirty minutes
      after bleeding, the mean arterial pressure decreased significantly and similarly
      in the three groups (25-30%). The placebo group had a significant decrease in
      cardiac output (CO) without significant change in systemic vascular resistance
      (SVR). Conversely, in the a-AT(1) group, SVR decreased significantly with a
      moderate change in CO and addition of the AT(2) antagonist to the AT(1)
      antagonist (a-AT(1-2) group) did not abolish the lowering in SVR. The results
      suggest that AT(2) receptor has only a small if any contribution in the
      vasodilatation observed in the AT(1)-blockade group.

PMID- 15519534
TI  - Effect of elevated intraocular pressure on endothelin-1 in a rat model of
      glaucoma.
AB  - The role of endothelin-1 (ET-1) a potent vasoactive peptide, in glaucoma
      pathogenesis is receiving increasing attention, particularly in astroglial
      activation in optic nerve damage. Our laboratory has also shown that ET-1
      treatment causes proliferation of cultured human optic nerve head astrocytes to
      possibly initiate astrogliosis. ET-1 is distributed in retina, optic nerve, and
      ciliary epithelium, however the effects of elevated intraocular pressure (IOP)
      (as seen in glaucoma) on ET-1 and ET(B) receptors are not clearly understood. In
      the present study, the levels of immunoreactive ET-1 (ir-ET-1) in aqueous humour
      (AH) and optic nerve head (ONH) were determined in the Morrison elevated IOP
      model of glaucoma. Additionally in the ONH of these rats, immunohistochemical
      analyses of ET(B) receptors and glial fibrillary acidic protein (GFAP; a marker
      for astroglial cells and for astrogliosis) were performed. There was 2- to 2.5
      fold increase in AH ir-ET-1 levels for rats subjected to elevated IOP, compared
      to their respective controls. In the Morrison rat model of glaucoma, elevated IOP
      increased optic nerve ir-ET-1 with concomitant increases in ir-ET(B) and ir-GFAP
      labelling (possibly indicative of astrogliosis and hypertrophy). As seen in brain
      astrocytes subjected to neurotrauma, the present findings are suggestive of ET
      1's role in astroglial activation, particularly in response to elevated IOP in
      glaucoma.

PMID- 15519535
TI  - Green tea extract attenuates cyclosporine A-induced oxidative stress in rats.
AB  - Cyclosporine A (CsA) nephrotoxicity underweighs the therapeutic benefits of such
      a powerful immunosuppressant. Whether oxidative stress plays a role in such
      toxicity is not well delineated. We investigated the potential of green tea
      extract (GTE) to attenuate CsA-induced renal dysfunction in rats. Three main
      groups of Sprague-Dawley rats were used: CsA, GTE, and GTE plus CsA-receiving
      animals. Corresponding control groups were also used. CsA was administered in a
      dose of 20mg kg(-1) day(-1), i.p., for 21 days. In the GTE/CsA groups, the rats
      received different concentrations of GTE (0.5, 1.0 and 1.5%), as their sole
      source of drinking water, 4 days before and 21 days concurrently with CsA. The
      GTE group was treated with 1.5% concentration of GTE only for 25 days. A
      concomitant administration of GTE, to CsA receiving rats, markedly prevented the
      generation of thiobarbituric acid-reacting substances (TBARS) and significantly
      attenuated CsA-induced renal dysfunction as assessed by estimating serum
      creatinine, blood urea nitrogen, uric acid and urinary excretion of glucose. A
      considerable improvement in terms of reduced glutathione content and activity of
      antioxidant enzymes in the kidney homogenate of the GTE/CsA-receiving rats was
      observed. The activity of lysosomal enzymes, N-acetyl-beta-glucosaminidase, beta
      glucuronidase and acid phosphatase was significantly inhibited following GTE co
      administration. Our data prove the role of oxidative stress in the pathogenesis
      of CsA-induced kidney dysfunction. Supplementation of GTE could be useful in
      reducing CsA nephrotoxicity in rats. However, clinical studies are warranted to
      investigate such an effect in human subjects.

PMID- 15519536
TI  - A study of unfractionated and low molecular weight heparins in a model of
      cholestatic liver injury in the rat.
AB  - Forty-eight rats with biliary obstruction induced by double ligation and section
      of the common bile duct were randomly and blindly assigned to receive
      subcutaneous injection of either conventional heparin sodium (1000IU kg(-1)),
      three already marketed low molecular weight heparin (LMWH) preparations:
      nadroparin (1000 anti-Xa IU kg(-1)), tinzaparin (1000 anti-Xa IU kg(-1)),
      enoxaparin (180 anti-Xa IU kg(-1)) or saline. Drugs were administered once a day,
      starting 7 days after surgery and continued for 3 weeks. At the end of the
      treatment period, rats were killed and analyzed for blood biochemistry and liver
      pathology. Liver fibrosis was assessed by image analysis. Data indicated that
      treatment with nadroparin decreased plasma total bilirubin, serum alkaline
      phosphatase (ALP) and gamma glutamyltransferase (GGT) levels by 80.3, 70.7 and
      42%, compared with bile duct ligated (BDL) control values. The reduction in
      plasma total protein observed in BDL controls was prevented by nadroparin.
      Enoxaparin-treated rats showed significant reduction in plasma total bilirubin
      and alanine aminotransferase levels by 32.5 and 38.4% versus BDL controls. Liver
      necrosis evaluated histologically was significantly reduced in the nadroparin-
      and enoxaparin-treated rats. Morphometric analysis showed significant reduction
      in fibrosis on nadroparin and enoxaparin treatment: area of fibrosis: 1.66 +/-
      0.17% and 14.03 +/- 1.1% versus 18.94 +/- 2.4% (P<0.05); nadroparin and
      enoxaparin versus BDL control. By contrast, neither conventional heparin nor
      tinzaparin prevented the bile duct ligation-induced liver damage as indicated by
      increased plasma aminotransferases, ALP and GGT concentrations and the
      histological evidence of necrosis. Total serum bilirubin was increased by 27.5%
      in rats treated with conventional heparin, while ALP and GGT levels were 38.6 and
      31.4% higher after tinzaparin treatment versus BDL controls. Significant increase
      in the area of fibrosis was observed after tinzaparin treatment compared to BDL
      control group. Results suggest a beneficial effect for nadroparin and enoxaparin
      in the therapy of patients with obstructive jaundice or cholestatic liver
      disorders. The present data from bile duct ligated rats suggest an antifibrotic
      effect for nadroparin and enoxaparin.

PMID- 15519537
TI  - Selegiline modifies the extinction of responding following morphine self
      administration, but does not alter cue-induced reinstatement, reacquisition of
      morphine reinforcement, or precipitated withdrawal.
AB  - Selegiline is an irreversible inhibitor of monoamine oxidase (MAO) with
      psychostimulant and neuroprotective effects which can prevent decreases in
      dopamine efflux that follow opiate withdrawal. The present study evaluated
      effects of selegiline treatment on morphine-seeking behavior and morphine
      reinforcement in Wistar rats (n = 26). In additional animals (n = 30), the
      ability of single doses of selegiline to modify naloxone-precipitated withdrawal
      was determined. After pretreatment with noncontingent morphine to establish
      opiate dependence, rats acquired self-administration of intravenous morphine.
      Daily intravenous treatment with saline or 2.0mg kg(-1) doses of selegiline was
      then initiated and continued over 14 days during extinction, reinstatement, and
      reacquisition of morphine self-administration. To reduce the potential for
      psychostimulant effects, selegiline was administered approximately 1h following
      self-administration, extinction, or reinstatement sessions. In some animals (n =
      23), effects of saline or selegiline administration on locomotor activity were
      determined following extinction sessions. Daily selegiline treatment decreased
      the number of ratios completed and increased response latency during extinction,
      without modifying these measures during reinstatement or reacquisition of
      morphine self-administration. Chronic selegiline treatment increased locomotor
      activity recorded between 4 and 7h after selegiline administration on day 7 of
      extinction, but otherwise did not alter locomotor activity. Pretreatment with
      single, 2.0mg kg(-1) doses of selegiline did not modify naloxone-precipitated
      withdrawal. In conclusion, pretreatment with selegiline produced only a small
      decrease in responding during extinction of morphine self-administration and did
      not modify cue-induced reinstatement of morphine-seeking behavior, reacquisition
      or morphine reinforcement, or precipitated withdrawal.

PMID- 15519538
TI  - Trazodone addition for insomnia in venlafaxine-treated, depressed inpatients: a
      semi-naturalistic study.
AB  - In this paper, we present the results of a prospective semi-naturalistic study of
      the addition of trazodone for insomnia to a 4 week, 300mg/day venlafaxine
      treatment in 50 depressed inpatients. The Montgomery and Asberg depression rating
      scale was used as a rating instrument. The study is designated as semi
      naturalistic due to the fact that, although the venlafaxine treatment regimen was
      strictly defined, the timing of the trazodone introduction and the dosage were
      determined by the clinicians. The indication was based on the persistency of
      insomnia despite the use of authorized sedative co-medication (zopiclone as a
      hypnotic, clorazepate as an anxiolytic). Among the 42 patients who completed the
      study, 27 did not receive trazodone (G1) while 15 did (G2). Although the two
      groups were not clinically different at study entry, G2 patients showed less
      improvement than G1 patients during venlafaxine treatment alone, both in terms of
      insomnia (MADRS item 4) and inner tension (MADRS item 3). After trazodone
      introduction, insomnia improved and the median (interquartile range) of this item
      in G1 and G2 patients showed no statistically significant difference on Day 28
      (G1: 0 (0-1); G2: 0 (0-2)). However, inner tension did not improve and the median
      (interquartile range) was higher on Day 28 in G2 patients (G1: 1 (0-2); G2: 2 (1
      4); P < 0.05). Thus, trazodone is probably used for patients who develop not only
      insomnia, but also inner tension/anxiety during venlafaxine treatment. However,
      it alleviates only the first symptom, not the second.

PMID- 15519539
TI  - Monoclonal antibodies specific to haemocytes of black tiger prawn Penaeus
      monodon.
AB  - Monoclonal antibodies specific to haemocytes of Penaeus monodon were generated
      from a mouse immunized with a mixture of SDS-treated and formalin-fixed
      haemocytes. Hybridoma clones were selected by immunohistochemistry against fixed
      haemocytes, heart, lymphoid organ, and haemopoietic tissue, and Western blot
      against haemocyte extract and haemolymph. Sixteen monoclonal antibodies specific
      to haemocytes were obtained and could be divided into six groups according to
      their binding capacities to various haemocyte proteins in Western blot analyses,
      102, 43, approximately 20, 61, 175 and approximately 230 kDa, and their
      differences in recognition of haemocyte sub-populations. The first group of
      antibodies strongly recognized a small subset of semi-granulocytes (SG) and
      hyalinocytes (H) but occasionally stained lightly a very small population of
      granulocytes (G). The antibodies also bound to a group of cells in haemopoietic
      tissue as well as cells located at the inner layers of the tubules in the
      lymphoid organ but not in the spheroid. The second group of antibodies strongly
      bound to a large sub-population of G and SG with coarse granules but did not bind
      to most of the H. This group of antibodies also cross-reacted with cells in the
      outer layer of the tubules in the lymphoid organ. The third group of antibodies
      recognized all G and only a small portion of SG. The fourth, fifth and sixth
      groups bound to sub-populations of G, SG and H in similar proportions. None of
      the antibodies showed any cross-reactivity to other components in haemolymph. The
      common antigens recognized by the first and the second groups of antibodies in
      the haemopoietic tissue and the lymphoid organ may reflect relationships among
      these organs in the development of the sub-populations of G and SG. Haemopoietic
      tissue may be the site for haemocyte production and the lymphoid organ may be the
      site for further differentiation of at least two different lines of haemocytes.

PMID- 15519540
TI  - Evolution and trans-species polymorphism of MHC class IIbeta genes in cyprinid
      fish.
AB  - The polymorphism of DAB genes encoding MHC IIbeta was investigated in 11 cyprinid
      species from central Europe. The species belonged to four subfamilies:
      Cyprininae, Tincinae, Gobioninae and Leuciscinae. Two paralogous groups of
      sequences, DAB1 and DAB3, were recognised according to the similarity of their
      nucleotide and amino-acid sequences and from phylogenetic analyses using either
      partial exon 2 or partial exon 3 sequences. A high allelic variability among
      species was found for exon 2, indicating extensive MHC polymorphism. Time
      divergence estimation supports the separation of DAB1 and DAB3 groups predating
      the separation into fish subfamilies, and a cyprinid origin of the DAB genes.
      Phylogenetic trees using exon 2 support the hypothesis of trans-species
      polymorphism, which appears to be limited to the subfamily level, i.e. the
      presence of sequences from different species in the same allelic group was more
      often recognised within subfamilies Cyprininae and Leuciscinae than between them.
      Phylogenetic trees using exon 3 reflect the phylogenetic patterns previously
      found for Cyprinidae systematics. Specific nucleotides and amino-acids in exon 3
      that separate both subfamilies, as well as the species within the Cyprininae
      subfamily were observed. A lack of segregation in leuciscin species was
      recognised and the alleles of different leuciscin species tend to share similar
      motifs in exon 3. This could be explained by the ancient and complicated
      dispersion history of Cyprininae and the radiation of Leuciscinae. The effects of
      selective pressures were investigated: (1) within species, (2) among lineages,
      and (3) among sites. From intraspecific analyses, exon 2 sequences were
      identified as the targets of diversifying selection, whilst the evolution of exon
      3 seems to be under the influence of purifying selection. The analyses among
      lineages indicate positive selection in many branches when using exon 2,
      therefore confirming trans-species polymorphism, whilst the DAB lineages of exon
      3 are potentially submitted to purifying selection to some extent. Moreover, our
      results suggest the secondary acquisition of function of DAB1 group after
      duplication. The analyses among sites reveal that exon 2 exhibits sites under
      positive selection mostly corresponding to the putative PBR sites involved in the
      alpha-helix structure of the protein.

PMID- 15519541
TI  - Modulation of the immune response to an Aeromonas hydrophila aroA live vaccine in
      rainbow trout: effect of culture media on the humoral immune response and
      complement consumption.
AB  - The Aeromonas hydrophila aroA is an attenuated strain that has been assessed as a
      live vaccine in rainbow trout, Oncorhynchus mykiss. In this study the effects of
      different culture media used to grow the strain on its survival after in vitro
      exposure to rainbow trout serum, and on its immunogenicity in rainbow trout were
      compared. Four culture media were tested: Luria broth (LB), Luria broth with
      0.25% glucose, trypticase soy broth (TSB), and brain-heart infusion broth (BHIB).
      Bacteria grown in culture media with glucose (TSB, BHIB and LB with 0.25%
      glucose) showed reduced complement consumption and a lower serum susceptibility.
      O. mykiss vaccinated with inocula prepared with BHIB- and LB-grown aroA cells
      resuspended in phosphate-buffered saline (PBS) showed higher and longer-lasting
      serum agglutinating antibody titres than those vaccinated with TSB-grown
      bacteria. Thus, a direct relationship between serum resistance and immunogenicity
      could not be established, but BHIB and LB culture media were the most effective
      in increasing the immunogenicity of the A. hydrophila aroA vaccine.

PMID- 15519542
TI  - Protection against experimental Aeromonas salmonicida infection in carp by oral
      immunisation with bacterial antigen entrapped liposomes.
AB  - Liposome-entrapped atypical Aeromonas salmonicida antigen was prepared to
      investigate the potential protective efficacy for A. salmonicida infection. Carp
      (Cyprinus carpio) were immunised orally with liposome-entrapped A. salmonicida
      antigen. After immunisation, significantly higher antigen-specific antibodies
      were detected in serum, intestinal mucus and bile than non-immunised control
      group. Furthermore, immunised carp were challenged by immersion with 1 x 10(6)
      cfu ml(-1) of A. salmonicida for 60 min. Of the eight non-immunised carp, three
      carp died (62.5% survival), whereas five out of six (83.5%) immunised survived.
      Furthermore, the development of skin ulcers was significantly inhibited in carp
      immunised with liposomes containing A. salmonicida antigen. These results suggest
      that liposomes containing A. salmonicida antigen have the potential for the
      induction of a protective immune response against atypical A. salmonicida
      infection and also suggest the possibility of developing a vaccine that may
      ultimately be used for the prevention of fish diseases.

PMID- 15519543
TI  - New MHC class Ia domain lineages in rainbow trout (Oncorhynchus mykiss) which are
      shared with other fish species.
AB  - Major histocompatibility complex (MHC) class Ia genes in salmonid fishes are
      encoded by a single locus with probably the highest allelic diversity ever
      described. Various combinations of very different domain lineages contribute to
      the diversity of alleles. An extensive PCR survey distinguishing most domain
      lineages and their combinations was established. This survey has practical value
      for researchers investigating salmonid MHC class Ia variation. In the present
      study it was used to find new domain lineages. Applied for 24 hatchery strains in
      Japan, the survey identified two new rainbow trout alpha1 lineages and one new
      rainbow trout alpha2 lineage. The alpha2 lineage and one of the alpha1 lineages
      had been described in Atlantic salmon, but the other alpha1 lineage is novel. The
      newly identified trout alpha1 lineages are evolutionary very old. The present
      study should be the most extensive description of very deep MHC class Ia lineages
      to date: six trout alpha1 lineages cluster with non-salmonid sequences whereas
      previous studies mentioned this for only two salmonid alpha1 lineages. Although
      exon-shuffling events significantly contributed to salmonid MHC class Ia
      variation, analysis of 800 trout siblings did not detect such events within a
      single generation.

PMID- 15519544
TI  - Salinity influences the humoral immune parameters of gilthead seabream (Sparus
      aurata L.).

PMID- 15519545
TI  - Gradient separation and cytochemical characterisation of neutrophils from kidney
      of fathead minnow (Pimephales promelas Rafinesque, 1820).

PMID- 15519546
TI  - Abstracts of the 8th Annual Meeting of the European Association of
      Echocardiography. Athens, Greece, 1-4 December 2004.

PMID- 15519547
TI  - The rhombencephalon and breathing: a view from the pons.

PMID- 15519548
TI  - Pontine influences on breathing: an overview.
AB  - Historical and contemporary views of the functional organization of the lateral
      pontine regions influencing breathing are reviewed. In vertebrates, the
      rhombencephalon generates a breathing rhythm and detailed motor pattern that
      persist throughout life. Key to this process is an essentially continuous column
      of neurons extending from the spino-medullary border through the ventrolateral
      medulla, continuing through the ventral pons and arcing into the dorsolateral
      medulla. Comparative neuroanatomy and physiology indicate this is a richly
      interconnected network divided into serial, functionally distinct compartments.
      Serial compartmentalization of pontomedullary structures related to breathing
      also reflects the developmental segmentation of the rhombencephalon. However,
      with migration of cell groups such as the facial nucleus from the pons to the
      medulla during ontogeny, the boundaries of the adult pons are sometimes difficult
      to precisely define. Accordingly, a working definition of rostral and caudal
      pontine boundaries for adult mammals is depicted.

PMID- 15519549
TI  - Functional organization of the parabrachial complex and intertrigeminal region in
      the control of breathing.
AB  - Although the medulla oblongata contains the epicenter for respiratory rhythm
      generation, many other parts of the neuraxis play significant substratal roles in
      breathing. Accumulating evidence suggests that the pons contains several groups
      of neurons that may belong to the central respiratory system. This article will
      review data from microstimulation mapping and tract-tracing studies of the
      parabrachial complex (PB) and intertrigeminal region (ITR). Chemical activation
      of neurons in these areas has distinct effects on ventilatory and airway muscle
      activity. Tract-tracing experiments from functionally identified sites reveal
      specific respiratory-related sensory inputs and outputs that are likely
      anatomical substrates for these effects. The data suggest that an important
      physiological role for the rostral pons may be reflexive respiratory responses to
      airway stimuli.

PMID- 15519550
TI  - Role in the inspiratory off-switch of vagal inputs to rostral pontine inspiratory
      modulated neurons.
AB  - Neurons of the pontine respiratory group (PRG) in the region of the nucleus
      parabrachialis medialis and the Kolliker-Fuse nucleus are believed to play an
      important role in promoting the inspiratory (I) off-switch (IOS). In decerebrate
      gallamine-paralyzed cats ventilated with a cycle-triggered pump system (lung
      inflation during the neural I phase), we studied the effects of vagal (V)
      afferent inputs on firing of I-modulated neurons (the most numerous population in
      PRG) and on I duration. The predominant V effect on unit activity was inhibitory,
      as shown by two types of test: (a) withholding of inflation during an I phase,
      which produced increase of unit firing and of its respiratory modulation (58/66
      neurons in 14 cats), indicating disinhibition due to removal of phasic V input;
      (b) delivery of afferent V stimulus trains during a no-inflation I phase, which
      produced decrease of unit firing and of its respiratory modulation (20 neurons).
      In addition, application of V input during the neural expiratory (E) phase, which
      lengthened E phase duration, produced no effect on the neurons' firing,
      suggesting that the inhibition during I was presynaptic in origin. The results
      may be interpreted by the hypothesis that the medullary late-I presumptive IOS
      neurons receive excitatory inputs from the PRG I-modulated neurons as well as
      from V afferents.. With relatively strong V input, this pontine excitatory output
      is reduced by inhibition, whereas with relatively weak V input that excitatory
      output is increased due to reduction of inhibition. Thus the pontine and the V
      influences on the IOS can operate in a complementary manner dependent on state.

PMID- 15519551
TI  - Pontine GABAergic pathways: role and plasticity in the hypoxic ventilatory
      response.
AB  - The hypoxic ventilatory response (HVR) was compared before and after uni- and bi
      lateral injections of bicuculline, a GABA(A) receptor antagonist, into the
      ventrolateral (vl) pons and before and after conditioning animals to chronic
      sustained hypoxia (CSH). The HVR was assessed by recording phrenic nerve activity
      (PNA) during and after brief exposures to hypoxia (8% O(2) and 92% N(2) for 45s).
      Inspiratory (T(I)) and expiratory (T(E)) durations were averaged before hypoxia,
      at the peak breathing frequency during hypoxia, before the end of hypoxia,
      immediately after hypoxia, and 60s after hypoxia. Blocking GABA(A) receptors in
      the vl pons prolonged T(E) during, but not after hypoxia. After CSH induced by 14
      days in a hypobaric chamber (0.5atm), the HVR was attenuated compared to that in
      the naive animals. This plasticity of HVR was associated with selective induction
      of alpha6 and delta GABA(A) receptor subunit mRNAs specifically in the pons
      compared to the medulla. These physiological and molecular results illustrate the
      importance of pontine GABAergic pathways in shaping the response to hypoxia.

PMID- 15519552
TI  - Development of adaptive behaviour of the respiratory network: implications for
      the pontine Kolliker-Fuse nucleus.
AB  - Breathing is constantly modulated by afferent sensory inputs in order to adapt to
      changes in behaviour and environment. The pontine respiratory group, in
      particular the Kolliker-Fuse nucleus, might be a key structure for adaptive
      behaviours of the respiratory network. Here, we review the anatomical
      connectivity of the Kolliker-Fuse nucleus with primary sensory structures and
      with the medullary respiratory centres and focus on the importance of pontine and
      medullary postinspiratory neurones in the mediation of respiratory reflexes.
      Furthermore, we will summarise recent findings from our group regarding
      ontogenetic changes of respiratory reflexes (e.g., the diving response) and
      provide evidence that immaturity of the Kolliker-Fuse nucleus might account in
      neonates for a lack of plasticity in sensory evoked modulations of respiratory
      activity. We propose that a subpopulation of neurones within the Kolliker-Fuse
      nucleus represent command neurones for sensory processing which are capable of
      initiating adaptive behaviour in the respiratory network. Recent data from our
      laboratory suggest that these command neurones undergo substantial postnatal
      maturation.

PMID- 15519553
TI  - Respiration-related afferents to parabrachial pontine regions.
AB  - The dorsolateral pons around the parabrachial nucleus is an important participant
      in respiratory control. This area involves various respiration-related neurons,
      and their respiratory modulation is thought to arise from afferents from
      medullary respiratory neurons. Today, however, only a limited number of afferent
      sources have been identified. First, relatively well-characterized afferents to
      the pons are those originating from two types of the lung stretch receptors,
      slowly adapting and rapidly adapting receptors. That is, the majority of the
      second-order relay neurons of these receptors in the nucleus tractus solitarii
      project to the pons. Second, certain types of respiratory neurons of the
      medullary respiratory groups are either known to or presumed to project to the
      pons. For instance, major inhibitory neurons of the Botzinger complex, augmenting
      and decrementing expiratory neurons, send afferents to the pons. This article
      overviews such afferents and discusses their connectivity with pontine neurons.

PMID- 15519554
TI  - Nucleus isthmi and control of breathing in amphibians.
AB  - Despite recent advances, the mechanisms of neurorespiratory control in amphibians
      are far from understood. One of the brainstem structures believed to play a key
      role in the ventilatory control of anuran amphibians is the nucleus isthmi (NI).
      This nucleus is a mesencephalic structure located between the roof of the
      midbrain and the cerebellum, which differentiates during metamorphosis; the
      period when pulmonary ventilation develops in bullfrogs. It has been recently
      suggested that the NI acts to inhibit hypoxic and hypercarbic drives in breathing
      by restricting increases in tidal volume. This data is similar to the influence
      of two pontine structures of mammals, the locus coeruleus and the nucleus raphe
      magnus. The putative mediators for this response are glutamate and nitric oxide.
      Microinjection of kynurenic acid (an ionotropic receptor antagonist of excitatory
      amino acids) and l-NAME (a non-selective NO synthase inhibitor) elicited
      increases in the ventilatory response to hypoxia and hypercarbia. This article
      reviews the available data on the role of the NI in the control of ventilation in
      amphibians.

PMID- 15519555
TI  - Modulation of the respiratory rhythm generator by the pontine noradrenergic A5
      and A6 groups in rodents.
AB  - The aim of the present review is to summarise available studies dealing with the
      respiratory control exerted by pontine noradrenergic neurones in neonatal and
      adult mammals. During the perinatal period, in vitro studies on neonatal rodents
      have shown that A5 and A6 neurones exert opposite modulations onto the
      respiratory rhythm generator, inhibitory and facilitatory respectively, that the
      anatomical support for these modulations already exists at birth, and that
      genetically induced alterations in the formation of A5 and A6 neurones affect the
      maturation of the respiratory rhythm generator, leading to lethal respiratory
      deficits at birth. The A5-A6 modulation of the respiratory rhythm generator is
      not transient, occurring solely during the perinatal period but it persists
      throughout life: A5 and A6 neurones display a respiratory-related activity,
      receive inputs from and send information to the medullary respiratory centres and
      contribute to the adaptation of adult breathing to physiological needs.

PMID- 15519556
TI  - Rhythms, synchrony and electrical coupling in the Locus coeruleus.
AB  - Electrical coupling of neurones is believed to promote synchronized activity. It
      may, however, also be a requirement for the maintenance of endogenous rhythmic
      activity in some systems. In en bloc isolated brainstem-spinal cord of the
      neonatal rat simultaneous whole cell recordings from pairs of LC neurones (n = 47
      pairs) disclosed for the most part strongly synchronized activity which could
      take the form of tonic spiking or phasic bursts. Simultaneous whole cell
      recording from LC neurones and glia also revealed synchronized waves of
      depolarization in 7 of 17 pairs. This synchrony was partly due to respiratory
      phased synaptic input and partly due to mechanisms, which were not dependent on
      chemical synapses. The gap junction uncoupler carbenoxolone suppressed non
      synaptic rhythmic activity in LC neurones, but did not suppress either
      respiratory-phased synaptic input to these neurones or their excitatory response
      to increased CO(2). We give preliminary direct evidence for the existence of a
      current pathway between LC neurones, which is inhibited by carbenoxolone. Within
      the LC nucleus carbenoxolone-sensitive electrical coupling, which may involve
      neurone-glia as well as neurone-neurone interactions, may be required not just
      for synchronization, but also for the maintenance of rhythm.

PMID- 15519557
TI  - Parabrachial-lateral pontine neurons link nociception and breathing.
AB  - We investigated the role of the parabrachial complex in cutaneous nociceptor
      induced respiratory stimulation in chloralose-urethane anesthetized, vagotomized
      rats. Noxious stimulation (mustard oil, MO) applied topically to a forelimb or
      hindlimb enhanced the peak amplitude of the integrated phrenic nerve discharge
      and, with forelimb application, increased phrenic nerve burst frequency.
      Bilateral inactivation of neural activity in the parabrachial complex with
      injection of the GABA agonist muscimol (3nl) markedly attenuated the response to
      MO application. Injection of the retrograde tracer FluoroGold within the
      medullary ventral respiratory column labeled neurons in dorsolateral pontine
      regions known to receive nociceptive inputs (i.e., Kolliker-Fuse, lateral
      crescent, and superior lateral subnuclei of the parabrachial complex).
      Extracellular recordings of 65 dorsolateral parabrachial neurons revealed about
      15% responded to a noxious cutaneous pinch with either an increase or a decrease
      in discharge and approximately 40% of these exhibited a phasic respiratory
      related component to their discharge. In conclusion, parabrachial pontine neurons
      contribute to cutaneous nociceptor-induced increases in breathing.

PMID- 15519558
TI  - Pontine cholinergic mechanisms and their impact on respiratory regulation.
AB  - Activation of pontomedullary cholinergic neurons may directly and indirectly
      cause depression of respiratory motoneuronal activity, activation of respiratory
      premotor neurons and acceleration of the respiratory rate during REM sleep, as
      well as activation of breathing during active wakefulness. These effects may be
      mediated by distinct subpopulations of cholinergic neurons. The relative
      inactivity of cholinergic neurons during slow-wave sleep also may contribute to
      the depressant effects of this state on breathing. Cholinergic muscarinic and
      nicotinic receptors are expressed in central respiratory neurons and motoneurons,
      thus allowing cholinergic neurons to act on the respiratory system directly.
      Additional effects of cholinergic activation are mediated indirectly by
      noradrenergic, serotonergic and other neurons of the reticular formation.
      Excitatory and suppressant respiratory effects with features of natural states of
      REM sleep or active wakefulness can be elicited in urethane-anesthetized rats by
      pontine microinjections of the cholinergic agonist, carbachol. Carbachol models
      help elucidate the neural basis of respiratory disorders associated with central
      cholinergic activation.

PMID- 15519559
TI  - Pontine and basal forebrain cholinergic interaction: implications for sleep and
      breathing.
AB  - Pontine and forebrain cholinergic nuclei contribute to the regulation of
      breathing and arousal. This report summarizes experiments in rat (n = 20)
      concerning the cholinergic interaction between pons and basal forebrain. In vitro
      [(35)S]guanylyl-5'-O-(gamma-thio)-triphosphate ([(35)S]GTPgammaS) autoradiography
      quantified carbachol-stimulated guanine nucleotide binding (G) protein activation
      in seven basal forebrain nuclei. Carbachol significantly increased
      [(35)S]GTPgammaS binding in the vertical and horizontal limbs of the diagonal
      band of Broca, medial and lateral septum, and nucleus basalis (B)/substantia
      innominata (SI). In vitro receptor autoradiography demonstrated muscarinic
      receptors in the same nuclei where carbachol caused G protein activation. In vivo
      experiments showed that carbachol administered to the pontine reticular formation
      (PnO) significantly decreased the number of 7-14Hz spindles in the
      electroencephalogram (EEG), decreased acetylcholine release in SI, and decreased
      respiratory rate. Carbachol microinjection into SI did not alter the number of
      EEG spindles or respiratory rate. The results help clarify that EEG and rate of
      breathing are more effectively modulated by cholinergic neurotransmission in PnO
      than in SI.

PMID- 15519560
TI  - Pontine influences on respiratory control in ectothermic and heterothermic
      vertebrates.
AB  - Respiratory rhythm generators appear both evolutionarily and developmentally as
      paired segmental rhythm generators in the reticular formation, associated with
      the motor nuclei of cranial nerves V, VII, IX, X, and XII. Those associated with
      the Vth and VIIth motor nuclei are "pontine" in origin and in fishes that employ
      a buccal suction/force pump for breathing the primary pair of respiratory rhythm
      generators are associated with the trigeminal nuclei. In amphibians, while the
      basic respiratory pump remains the same, the dominant site of respiratory rhythm
      generation has been assumed by the facial, glossopharyngeal and vagal motor
      nuclei. In reptiles, birds and mammals, in general there is a switch to an
      aspiration pump driven by thoraco-lumbar muscles innervated by spinal nerves. In
      these groups, the critical sites necessary for respiratory rhythmogenesis now sit
      near the ponto-medullary border, in the parafacial region (which may underlie
      expiratory-dominated, intercostal-abdominal breathing in non-mammalian tetrapods)
      and in a more caudal region, the preBotzinger complex (which may underlie
      inspiratory-dominated diaphragmatic breathing in mammals).

PMID- 15519561
TI  - Functional and structural models of pontine modulation of mechanoreceptor and
      chemoreceptor reflexes.
AB  - The dorsolateral and ventrolateral pons (dl-pons, vl-pons) are critical brainstem
      structures mediating the plasticity of the Hering-Breuer mechanoreflex (HBR) and
      carotid chemoreflex (CCR). Review of anatomical evidence indicates that dl-pons
      and vl-pons are connected reciprocally with one another and with medullary
      nucleus tractus solitarius (NTS) and ventral respiratory group (VRG). With this
      structural map, functional models of HBR and CCR are proposed in which the
      respiratory rhythm is modulated by short-term depression (STD) or potentiation
      (STP) of corresponding primary NTS-VRG and auxiliary pons-VRG excitatory or
      inhibitory pathways. Behaviorally, STD and STP of respiratory reflexes are akin
      to non-associative learning such as habituation, sensitization or desensitization
      to afferent inputs. Computationally, the STD and STP effects amount to signal
      differentiation and integration in the time domain, or high-pass and low-pass
      filtering in the frequency domain, respectively. These functional and structural
      models of pontomedullary signal processing provide a novel conceptual framework
      that unifies a wealth of experimental observations regarding mechanoreceptor and
      chemoreceptor reflex control of breathing.

PMID- 15519562
TI  - Modulation of reflex and sleep related apnea by pedunculopontine tegmental and
      intertrigeminal neurons.
AB  - We describe and summarize here our recent findings about the role in respiration
      of two pontine structures that are not classically included in the pontine
      respiratory group: the pedunculopontine tegmental nucleus (PPT) and the
      intertrigeminal region (ITR). We also discuss significant contributions of other
      workers in the field, especially, S. Datta [Cell. Mol. Neurobiol. 17: 341-365,
      1997], R. Lydic and H. Baghdoyan [Sleep, 25: 617-622, 2002], and N. Chamberlin
      and C. Saper [J. Neurosci. 18: 6048-6056, 1998], who postulated a role for the
      ITR in modulating reflex apnea. In anesthetized and freely moving rats we have
      consistently documented that PPT and ITR have a role in respiration.
      Neurochemical manipulations of each area affected the brainstem respiratory
      pattern generator and respiratory pattern variability,observed as spontaneous
      disturbances during sleep or as induced reflex apnea. Although the exact central
      mechanisms of apnea cannot be determined from our studies to date, we postulate
      that reflex and sleep-related apneas in rats share some common brainstem
      pathways, which may include PPT and ITR.

PMID- 15519563
TI  - Modeling the ponto-medullary respiratory network.
AB  - The generation and shaping of the respiratory motor pattern are performed in the
      lower brainstem and involve neuronal interactions within the medulla and between
      the medulla and pons. A computational model of the ponto-medullary respiratory
      network has been developed by incorporating existing experimental data on the
      medullary neural circuits and possible interactions between the medulla and pons.
      The model reproduces a number of experimental findings concerning alterations of
      the respiratory pattern following various perturbations/stimulations applied to
      the pons and pulmonary afferents. The results of modeling support the concept
      that eupneic respiratory rhythm generation requires contribution of the pons
      whereas a gasping-like rhythm (and the rhythm observed in vitro) may be generated
      within the medulla and involve pacemaker-driven mechanisms localized within the
      medullary pre-Botzinger Complex. The model and experimental data described
      support the concept that during eupnea the respiration-related pontine structures
      control the medullary network mechanisms for respiratory phase transitions,
      suppress the intrinsic pacemaker-driven oscillations in the pre-BotC and provide
      inspiration-inhibitory and expiration-facilitatory reflexes which are independent
      of the pulmonary Hering-Breuer reflex but operate through the same medullary
      phase switching circuits.

PMID- 15519564
TI  - Role of pontile mechanisms in the neurogenesis of eupnea.
AB  - We have proposed a "switching concept" for the neurogenesis of ventilatory
      activity. Eupnea reflects the output of a pontomedullary neuronal circuit,
      whereas gasping is generated by medullary pacemaker mechanisms. Pontile
      mechanisms, then, are hypothesized to play a fundamental role in the neurogenesis
      of eupnea. If pontile mechanisms do play such a critical role, several criteria
      must be fulfilled. First, perturbations of pontile regions must alter eupnea
      under all experimental conditions. Second, neuronal activities that are
      consistent with generating the eupneic rhythm must be recorded in pons. Finally,
      medullary mechanisms alone cannot fully explain the neurogenesis of eupnea.
      Evidence from previous studies that support the validity of these criteria is
      presented herein. We conclude that pontile mechanisms play a critical role in the
      neurogenesis of eupnea.

PMID- 15519565
TI  - Equivalence test in quantitative reverse transcription polymerase chain reaction:
      confirmation of reference genes suitable for normalization.
AB  - In quantitative reverse transcription-polymerase chain reaction (qRT-PCR),
      normalization using reference genes is a common useful approach, but the
      validation of suitable reference genes remains a crucial problem. Use of
      unconfirmed reference genes may lead to misinterpretation of the expression of
      target genes. The aim of this study was to adapt an adequate statistical approach
      to identify and validate reference genes suitable for normalization in qRT-PCR
      assays. We introduce the equivalence test for the identification of stably
      expressed reference genes. To evaluate the advantages of this test, the
      expression of five genes widely used as reference genes (18S, B2M, HPRT1, LMNB1,
      and SDHA), and of two target genes (TP53 and MMP2), was determined with qRT-PCR
      in different tissues (clear cell renal cell carcinoma, colon carcinoma, and
      gastrointestinal stromal tumors). We demonstrate that a stable expression of a
      reference gene in one tumor type does not predict a stable expression in another
      tumor type. In addition, we found that even within one tumor type, the expression
      of a reference gene was not stable for different biological groupwise
      comparisons. These observations confirm that there is no universal reference gene
      and underline the importance of specific validation of potential reference genes
      for any experimental condition.

PMID- 15519566
TI  - N-linked oligosaccharide analysis of glycoprotein bands from isoelectric focusing
      gels.
AB  - Glycoproteins often display a complex isoelectric focusing profile because of the
      presence of negatively charged carbohydrates, such as sialic acid, phosphorylated
      mannose, and sulfated GalNAc. Until now, understanding the role of these charged
      carbohydrates in determining the isoelectric focusing profile has been limited to
      observing pattern shifts following complete removal of the sugars in question. We
      have developed a simple and sensitive method for analyzing N-linked
      oligosaccharides from the individual isoelectric focusing bands of a glycoprotein
      using recombinant human thyroid-stimulating hormone as a model system. N-linked
      oligosaccharides were released and profiled from individual bands following
      electroblotting of isoelectric focusing gels. As might be predicted, high-pH
      anion-exchange chromatography-pulsed amperometric detection and matrix-assisted
      laser desorption/ionization-time of flight analyses indicated that the bands that
      migrated closer to the positive electrode contained more sialylated N-linked
      oligosaccharides. The sialic acid content of these bands correlated with that
      predicted from the corresponding oligosaccharide analyses.

PMID- 15519567
TI  - Mass spectrometric pathway monitoring of secondary metabolites: systematic
      analysis of culture extracts of Streptomyces species.
AB  - Streptomyces spheroides, Streptomyces rishiriensis, and Streptomyces
      roseochromogenes are producers of the aminocoumarin-type antibiotics novobiocin,
      coumermycin A(1), and clorobiocin, respectively, all of which are bacterial
      gyrase inhibitors. In an attempt to develop a general analytical method for
      pathway monitoring of secondary metabolites from culture extracts of these
      strains, we used superior mass spectrometric methods. The aim was to develop and
      apply a technique for the rapid analysis of Streptomyces culture extracts with
      respect to those substances, thereby providing a method for screening extracts of
      genetically modified strains for new pharmaceutically active antibiotics with
      improved pharmacological effects. The combination of full scan mass spectrometry
      (MS), parent ion scan MS, product ion scan MS, and in-source collision-induced
      fragmentation prior to product ion scans (pseudo-MS(3) scan), using
      characteristic fragmentation of the central aminocoumarin unit, was employed for
      the detection and structural interpretation of expected and new intermediates. We
      were able to show the applicability of this methodology to the three culture
      extracts, where the main intermediates could be found, and to demonstrate its use
      for interpretation of secondary metabolite biosynthesis. Some new compounds were
      discovered, including bis-carbamoylated novobiocin, hydroxylated clorobiocin, and
      several structurally and not yet fully elucidated coumermycin derivatives or
      precursors.

PMID- 15519568
TI  - Reference genes identified in SH-SY5Y cells using custom-made gene arrays with
      validation by quantitative polymerase chain reaction.
AB  - Transcriptomic methods are widely used as an initial approach to gain a
      mechanistic insight into physiological and pathological processes. Because
      differences in gene regulation to be assessed by RNA screening methods (e.g.,
      SAGE, Affymetrix GeneChips) can be very subtle, these techniques require stable
      reference genes for accurate normalization. It is widely known that housekeeping
      genes, which are routinely used for normalization, can vary significantly
      depending on the tissue, and experimental test. In this study, we aimed at
      identifying stable reference genes for a fibrillar Abeta(42) peptide-treated,
      human tau-expressing SH-SY5Y neuroblastoma cell line derived to model aspects of
      Alzheimer's disease in tissue culture. We selected genes exhibiting potential
      normalization characteristics from public databases to create a custom-made
      microarray allowing the identification of reference genes for low, intermediate,
      and abundant mRNAs. A subset of these candidates was subjected to quantitative
      real-time polymerase chain reaction and was analyzed with geNorm software. By
      doing so, we were able to identify GAPD, M-RIP, and POLR2F as stable and usable
      reference genes irrespective of differentiation status and Abeta(42) treatment.

PMID- 15519569
TI  - Development of a homogeneous binding assay for histamine receptors.
AB  - Histamine is critically involved in a wide range of physiological and
      pathological processes through its actions at different receptors. Thus,
      histamine receptors have been actively pursued as therapeutic targets in the
      pharmaceutical industry for the treatment of a variety of diseases. There are
      currently four histamine receptors that have been cloned, all of which are G
      protein-coupled receptors. Studies from both academia and pharmaceutical
      companies have identified compounds that modulate the function of specific
      histamine receptors. These efforts led to the successful introduction of
      histamine H(1) and H(2) receptor antagonists for the treatment of allergy and
      excess gastric acid secretion, respectively. Histamine H(3) receptor ligands are
      currently under investigation for the treatment of obesity and neurological
      disorders. The recently identified histamine H(4) receptor is preferentially
      expressed in the immune tissues, suggesting a potential role in normal immune
      functions and possibly in the pathogenesis of inflammatory diseases. Even with
      the long history of histamine research and the important applications of
      histamine receptor ligands, assays to measure the affinity of compounds binding
      to histamine receptors are still routinely analyzed using a filtration assay, a
      very low-throughput assay involving washing and filtration steps. This article
      describes a simple, robust, and homogeneous binding assay based on the
      scintillation proximity assay (SPA) technology that provides results equivalent
      to those obtained using the more complex filtration assay. The SPA format is
      easily adapted to high-throughput screening because it is amenable to automation.
      In summary, this technique allows high-throughput screening of compounds against
      multiple histamine receptors and, thus, facilitates drug discovery efforts.

PMID- 15519570
TI  - Custom chemical microarray production and affinity fingerprinting for the S1
      pocket of factor VIIa.
AB  - The goal of this study was to explore the applicability of surface plasmon
      resonance (SPR)-based fragment screening to identify compounds that bind to
      factor VIIa (FVIIa). Based on pharmacophore models virtual screening approaches,
      we selected fragments anticipated to have a reasonable chance of binding to the
      S1-binding pocket of FVIIa and immobilized these compounds on microarrays. In
      affinity fingerprinting experiments, a number of compounds were identified to be
      specifically interacting with FVIIa and shown to fall into four structural
      classes. The results demonstrate that the chemical microarray technology platform
      using SPR detection generates unique chemobiological information that is useful
      for de novo discovery and lead development and allows the detection of weak
      interactions with ligands of low molecular weight.

PMID- 15519571
TI  - Detection of mRNA degradation intermediates in tissues using the 3'-end poly(A)
      tailing polymerase chain reaction method.
AB  - It has become increasingly clear that mRNA stability is an important determinant
      of mRNA abundance in virtually all organisms. Although our understanding of
      prokaryotic lower eukaryotic mRNA stability mechanisms has progressed
      considerably, little is known about mammalian mRNA stability mechanisms,
      particularly at the tissue and animal levels. This is due largely to the lack of
      suitable methods to approach the problem. In this study, we have developed and
      refined the 3'-end poly(A)-tailing polymerase chain reaction (PCR) method to
      detect degradation intermediates in vivo. Using an in vitro transcribed RNA as a
      template, we found that the method could be used to detect a homogeneous pool of
      RNA down to 0.1 ng. The addition of 10 microg of total RNA from tissues decreased
      the sensitivity limit to 4 ng. Detection limits of the technique were determined
      precisely by varying the concentrations of in vitro transcribed RNA in a constant
      amount of total RNA and varying the concentration of total RNA while maintaining
      a constant amount of in vitro transcribed RNA. Our overall results showed that
      the poly(A)-tailing PCR method could be used to detect specific RNA species of
      approximately 1000 nt in a pool of heterogeneous RNA in the range of 1 in 2500 to
      1 in 10,000. To our knowledge, this is the most sensitive method to date for
      identifying mRNA degradation intermediates. Employing sense strand gene-specific
      primers in this method, we have discovered the class II and class III P
      glycoprotein (Pgp) mRNA degradation intermediates in normal rat tissues. This
      method should serve as an additional tool to help us understand mRNA decay
      mechanisms in tissues and at animal levels.

PMID- 15519572
TI  - Evaluation of enzymatic assays and compounds affecting ATP production in
      mitochondrial respiratory chain complex I deficiency.
AB  - Isolated complex I deficiency is the most common oxidative phosphorylation defect
      and is associated with substantial morbidity and mortality. The diagnosis is made
      by enzymatic analysis and for most patients the molecular pathology remains
      undefined. Various cofactors and vitamins are frequently administered, but their
      efficacy have been difficult to assess. We employed determination of ATP
      production in fibroblast cell lines from patients with complex I deficiency to
      evaluate the usefulness of therapeutic agents. The effect of each additive varied
      among the different patients with certain agents favorably affecting ATP
      production rate in some of the patients and adversely affecting it in others. The
      reduced nicotinamide adenine dinucleotide (NADH)-ferricyanide reductase assay in
      muscle mitochondria correlated better than the NADH-coenzyme Q and NADH
      cytochrome c assays with ATP production rate in fibroblasts. Our results
      underscore the necessity of evaluation of different agents for each patient
      separately. The NADH-ferricyanide reductase assay play a helpful role in
      directing mutation analysis and identifying patients which are more likely to
      have their cells amenable for ATP production assessment.

PMID- 15519573
TI  - DRESSA: biosensing of dioxin and dioxin-like chemicals using secreted alkaline
      phosphatase.
AB  - In this article, we describe a highly sensitive biosensing system, DRESSA, for
      detection of dioxin and dioxin-like chemicals. Tandem copies of the dioxin
      responsive element (DRE) fused to a minimal viral promoter were subcloned into an
      expression plasmid upstream of a secreted alkaline phosphatase (SEAP) gene. When
      murine hepatoma cell line Hepa-1c1c7 was stably transfected with this construct,
      established sensor clones secreted SEAP following stimulation with 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD). A clone HeDS49 was found to be extremely
      sensitive; it secreted SEAP in response to TCDD in dose- and time-dependent
      manners, and the minimal detection limit was 100 fM. To detect more than 6 pM of
      TCDD, the whole assay time (from cell seeding to measurement of SEAP activity)
      could be reduced to 4h. Secretion of SEAP was induced selectively by other
      activators of DRE (3-methylcholanthrene, benzo[a]pyrene, and beta-naphthoflavone)
      but not by activators of unrelated responsive elements. These data suggested that
      because of the rapidity, easiness, specificity, and high sensitivity of DRESSA,
      it is more suitable than currently available detection systems for dioxin and
      dioxin-like chemicals and would be of great advantage to high-throughput
      screening of these pollutants in environmental samples.

PMID- 15519574
TI  - Alzheimer's beta-peptide oligomer formation at physiologic concentrations.
AB  - When diluted from dimethyl sulfoxide or 1,1,1,3,3,3-hexafluoro-2-propanol,
      synthetic human Abeta(1-42) readily forms oligomeric structures at near
      physiologic concentrations (1-20 nM). Oligomers 40 kDa are detected in a sandwich
      enzyme-linked immunosorbant assay where the capture and detection antibodies
      recognize the same primary sequence epitope. Monomeric peptide with a single
      epitope does not react in this format. Abeta(1-40) peptide does not oligomerize
      readily under these conditions. The rate of oligomer formation has a steep linear
      temperature dependence but is weakly affected by ionic strength up to 0.5M NaCl
      or KCl. Oligomer formation is inhibited by concentrations of Tween 20 and several
      other detergents well below their critical micelle concentrations. Once formed,
      high-molecular-weight oligomers are stabilized by Tween 20. Gel permeation
      chromatography of an oligomer preparation formed at nanomolar concentrations
      indicates that the majority of the Abeta(1-42) peptide chromatographs as
      monomers/dimers of apparent mw approximately 10 kDa. The most abundant oligomers
      have apparent mobilities corresponding to 220 kDa (48-mer) and higher multiples
      of this without detectable concentrations of intermediate low-molecular-weight
      species. Very little immunoreactive peptide appears in the void volume (>1.5 MDa)
      of a Superose 12 column. The oligomers are stable, rechromatographing at their
      original position. Abeta(1-42) oligomer formation at physiologic concentrations
      is a reproducible process that is amenable to kinetic analysis and inhibition.

PMID- 15519575
TI  - Phenylalanine hydroxylase: possible involvement in the S-oxidation of S
      carboxymethyl-l-cysteine.
AB  - Activated phenylalanine 4-monooxygenase, phenylalanine hydroxylase (PAH), is
      known to be involved in the S-oxidation of a number of sulfide compounds. One of
      these compounds, S-carboxymethyl-l-cysteine (SCMC), is currently used for the
      treatment of chronic obstructive pulmonary disease and otitis media with effusion
      as a mucolytic agent, and the S-oxides are the major metabolites found in urine.
      However, the enzyme catalyzing the S-oxidation of SCMC has yet to be identified.
      Here we report on the role of nonactivated phenylalanine 4-monooxygenase activity
      in rat liver cytosol in the S-oxidation of SCMC. Linearity of the enzyme assays
      was seen for both time (0-16 min) and cytosolic protein concentration (0.1
      0.5mg/ml). The calculated K(m) and V(max) values for the formation of SCMC (S) S
      oxide were 3.92+/-0.15 mM and 1.10+/-0.12 nmol SCMC (S) S-oxide formed/mg
      protein/min, respectively. The calculated K(m) and V(max) values for the
      formation of SCMC (R) S-oxide were 9.18+/-1.13 mM and 0.46+/-0.11 nmol SCMC (R) S
      oxide formed/mg protein/min, respectively. These results indicate that in the
      female Wistar rat, nonactivated PAH showed a stereospecific preference for the
      formation of the (S) S-oxide metabolite of SCMC against the (R) S-oxide
      metabolite of SCMC.

PMID- 15519576
TI  - Quantification of sodium dodecyl sulfate in microliter biochemical samples by gas
      chromatography.
AB  - A novel gas chromatography (GC) method has been developed to accurately
      quantitate sodium dodecyl sulfate (SDS) in aqueous biochemical samples. This
      method is based on the quantitative conversion of SDS to 1-dodecanol in the GC
      injection port at elevated temperature, and the thermal degradation product 1
      dodecanol was analyzed to determine SDS concentration. It was found that the
      addition of guanidinium chloride (GnHCl) to SDS samples (via direct dilution with
      GnHCl/MeOH solution) is necessary to ensure accurate quantitation. The presence
      of GnHCl enables quantitative conversion of SDS to 1-dodecanol, improves
      sensitivity, and virtually eliminates interference from proteins and other
      chemicals commonly present in biochemical samples. The method features direct
      analysis of diluted SDS samples, is free from interference, and is capable of
      quantifying less than 1 ng SDS in biochemical samples. It is also suitable for
      samples with limited volume, with as little as 1 microl sample being sufficient
      for quantitation.

PMID- 15519577
TI  - A high-performance liquid chromatography method for determining transition metal
      content in proteins.
AB  - Transition metals are common components of cellular proteins and the detailed
      study of metalloproteins necessitates the identification and quantification of
      bound metal ions. Screening for metals is also an informative step in the initial
      characterization of the numerous unknown and unclassified proteins now coming
      through the proteomic pipeline. We have developed a high-performance liquid
      chromatography method for the quantitative determination of the most prevalent
      biological transition metals: manganese, iron, cobalt, nickel, copper, and zinc.
      The method is accurate and simple and can be adapted for automated high
      throughput studies. The metal analysis involves acid hydrolysis to release the
      metal ions into solution, followed by ion separation on a mixed-bead ion-exchange
      column and absorbance detection after postcolumn derivatization with the
      metallochromic indicator 4-(2-pyridylazo)resorcinol. The potential interferences
      by common components of protein solutions were investigated. The metal content of
      a variety of metalloproteins was analyzed and the data were compared to data
      obtained from inductively coupled plasma-atomic emission spectroscopy. The
      sensitivity of the assay allows for the detection of 0.1-0.8 nmol, depending on
      the metal. The amount of protein required is governed by the size of the protein
      and the fraction of protein with metal bound. For routine analysis 50 microg was
      used but for many proteins 10 microg would be sufficient. The advantages,
      disadvantages, and possible applications of this method are discussed.

PMID- 15519578
TI  - Resonant mirror biosensor detection method based on yessotoxin-phosphodiesterase
      interactions.
AB  - Yessotoxin (YTX) is a generic name for a group of lipophilic compounds recently
      discovered and chemically characterized. Association measurements were done in a
      resonant mirror biosensor. The instrument detects changes in the refractive index
      and/or thickness occurring within a few hundred nanometers form the sensor
      surface where a molecule is attached. We used aminosilane surfaces where
      phosphodiesterase 3',5'-cyclic-nucleotide-specific from bovine brain (PDEs) was
      immobilized. Over this immobilized ligand different amounts of YTX were added and
      typical association curve profiles were observed. These association curves fit a
      pseudo-first-order kinetic equation where the apparent association rate constant
      (k(on)) can be calculated. The value of this constant increases with YTX
      concentration. From the representation of k(on) versus YTX concentration we
      obtained the association rate constant (k(ass)) 248+/-40 M(-1)s(-1) and the
      dissociation rate constant (k(diss)) 9.36 x 10(-4)+/-1.72 x 10(-4)s(-1). From
      these values the kinetic equilibrium dissociation constant (K(D)) for YTX-PDEs
      association can be calculated. The value of this last constant is 3.74 x 10(-6)+/
      8.25 x 10(-8)M YTX. The PDE-YTX association was used as a method suitable for
      determination of the toxin concentration in a shellfish sample. The assay had
      sufficient sensitivity and can be used on simple shellfish extracts.

PMID- 15519579
TI  - Amino acid analysis in mammalian cell culture media containing serum and high
      glucose concentrations by anion exchange chromatography and integrated pulsed
      amperometric detection.
AB  - The direct separation detection of amino acids by anion exchange chromatography
      with integrated pulsed amperometric detection was optimized for the analysis of
      typical mammalian cell culture broth samples. Existing gradient elution
      conditions were adapted, considering the additions of peptone (2 g/L) and 10 vol%
      fetal calf serum to the medium as well as changing concentrations of glucose from
      5.5 g/L up to complete consumption. Samples had to be analyzed in two dilutions
      with water (1:33.3 and 1:200) due to the strongly varying amino acid
      concentrations in the samples as a result of the medium composition and cell
      metabolism. The method was validated in a linear working range for the most
      common amino acids (2.5-7.5 and 1.25-3.75 microM for cystine/cysteine with 15
      microl injection volume). The relative standard deviation of the method for all
      amino acids was less than 5%, with detection limits of less than 0.6 microM and
      quantitation limits of less than 1.6 microM. As an example, data for the amino
      acid composition of different media used for the production of inactivated
      influenza vaccines in cell culture are shown.

PMID- 15519580
TI  - N-[3H]Benzoylglycylglycylglycine as a probe for hydroxyl radicals.
AB  - N-[4-(3)H]Benzoylglycylglycylglycine ([(3)H]BzG(3)) was tested as a probe for
      detecting hydroxyl radicals (*OH). Aerated solutions of l-ascorbate generated
      *OH, which oxidized [(3)H]BzG(3), yielding hydrophilic (probably hydroxylated)
      derivatives plus tritiated water. The (3)H(2)O was separated from organic
      products and remaining [(3)H]BzG(3) on Dowex-1. (3)H(2)O production was much
      greater with *OH than with other reactive oxygen species (ROS) (e.g., H(2)O(2),
      superoxide). The slight (3)H(2)O production in the presence of H(2)O(2) or
      superoxide was blocked by *OH scavengers (e.g., glycerol, mannitol, butan-1-ol)
      that do not scavenge H(2)O(2) or superoxide. This indicates that (3)H(2)O
      production was caused by *OH and that other ROS only generated any (3)H(2)O by
      forming traces of *OH. Doses of *OH that caused detectable nonenzymic
      polysaccharide scission also caused (3)H(2)O production, indicating that
      [(3)H]BzG(3) is a sensitive *OH probe in studies of polymer scission. The ability
      of scavengers and chelators to protect against ascorbate-mediated polysaccharide
      scission paralleled their ability to inhibit concurrent (3)H(2)O production,
      indicating that both processes were due to *OH. Thus, [(3)H]BzG(3) is a simple,
      specific, sensitive, and robust probe for detecting *OH production in vitro. It
      may have applications for in vivo detection of extracellular *OH in arthritic
      joints and of apoplastic *OH in plant cell walls.

PMID- 15519581
TI  - Mechanism of enzymatic degradation of the azo dye Orange II determined by ex situ
      1H nuclear magnetic resonance and electrospray ionization-ion trap mass
      spectrometry.
AB  - Removal of azo dye effluents generated by textile photography industries is a
      main issue in wastewater treatment. Enzymatic treatment of dyes appears to be one
      of the most efficient processes for their degradation. The elucidation of
      degradation pathways is of special interest considering health and environmental
      priorities. Ex situ nuclear magnetic resonance (NMR) spectroscopy and
      electrospray ionization (ESI)-ion trap mass spectrometry performed directly on
      incubation medium have been used for the first time to follow kinetics of
      sulfonated azo dye Orange II enzymatic degradation. Nine transformation products
      were identified using these complementary analyses performed ex situ without any
      prior treatment. Three types of cleavage are proposed for the degradation
      pathway: (i) a symmetrical splitting of the azo linkage that leads to the
      formation of 4-aminobenzenesulfonate (and 1-amino-2-naphthol, not detected); (ii)
      an asymmetrical cleavage on the naphthalene side that generates 1,2
      naphthoquinone and 4-diazoniumbenzenesulfonate as products, with the latter one
      being transformed into 4-hydroxybenzensulfonate; and (iii) a third degradation
      pathway that leads to 2-naphthol and 4-hydroxybenzenesulfonate. Moreover, three
      other intermediates have been identified. This study, which constitutes the first
      concomitant use of (1)H NMR spectroscopy and ESI-ion trap mass spectrometry in
      this field, illustrates the indubitable interest of the ex situ approach.

PMID- 15519582
TI  - A strategy for establishing accurate quantitation standards of oligonucleotides:
      quantitation of phosphorus of DNA phosphodiester bonds using inductively coupled
      plasma-optical emission spectroscopy.
AB  - A novel approach for quantitation of DNA (oligonucleotides) with an unprecedented
      accuracy of approximately 1% is reported. Quantitation of DNA is commonly
      performed by measuring UV absorption or fluorescence from dyes intercalated into
      DNA. Both methods need accurate quantitation standards to yield more comparable
      results between laboratories. For establishing technically authentic standards
      for DNA quantitation, a new measurement approach carrying an inherent capability
      of absolute quantitation is demanded. The proposed approach is based on the
      stoichiometric existence of phosphorus (P) in DNA. The quantity of P from the
      phosphodiester backbone of a purified oligonucleotide was accurately determined
      using inductively coupled plasma-optical emission spectroscopy (ICP-OES) with
      yttrium internal standard via acid digestion. The number of moles of
      oligonucleotides was then calculated from that of P using the stoichiometry. The
      major issues regarding the validity of the suggested approach were (i) effective
      removal of extra P sources, (ii) quantitative recovery of P through the digestion
      process, and (iii) oligomeric purity of the target oligonucleotide. These issues
      were investigated experimentally using various analytical techniques such as
      matrix-assisted laser desorption/ionization-time of flight mass spectrometry
      (MALDI-TOF MS), capillary electrophoresis, electrical conductometry, UV
      spectrometry, and gravimetry. In conclusion, it is feasible to certify pure
      oligonucleotide reference materials with uncertainties less than 1% using the
      proposed approach.

PMID- 15519583
TI  - Fibronectin in collaboration with Mg2+ enhances transgene expression by calcium
      phosphate coprecipitates.

PMID- 15519584
TI  - High-throughput molecular haplotype analysis (allelic assignment) of single
      nucleotide polymorphisms by fluorescent polymerase chain reaction.

PMID- 15519585
TI  - General method for facile intramolecular disulfide formation in synthetic
      peptides.

PMID- 15519586
TI  - Immortalization of mouse melanocytes carrying mutations in various pigmentation
      genes.

PMID- 15519587
TI  - Thermal analysis of bone cement polymerisation at the cement-bone interface.
AB  - The two major problems that have been reported with the use of
      polymethylmethacrylate (PMMA) cement are thermal necrosis of surrounding bone due
      to the high heat generation during polymerisation and chemical necrosis due to
      unreacted monomer release. Computer models have been used to study the
      temperature and monomer distribution after cementation. In most of these models,
      however, polymerisation is modelled as temperature independent and cancellous
      bone is modelled as a continuum. Such models thus cannot account for the expected
      important role of the trabecular bone micro-structure. The aim of this study is
      to investigate the distribution of temperature and monomer leftover at the
      cancellous bone-cement interface during polymerisation for a realistic trabecular
      bone-cement micro-structure and realistic temperature-dependent polymerisation
      kinetics behaviour. A 3-D computer model of a piece of bovine cancellous bone
      that underwent pressurization with bone-cement was generated using a micro
      computed tomography scanner. This geometry was used as the basis for a finite
      element model and a temperature-dependent problem for bone cement polymerisation
      kinetics was solved to simulate the bone cement polymerisation process in the
      vicinity of the interface. The transient temperature field throughout the
      interface was calculated, along with the polymerisation fraction distribution in
      the cement domain. The calculations revealed that the tips of the bone trabeculae
      that are embedded in the cement attain temperatures much higher than the average
      temperature of the bone volume. A small fraction of the bone (10%) is exposed to
      temperatures exceeding 70 degrees C, but the exposure time to these high
      temperatures is limited to 50s. In the region near the bone, the cement
      polymerisation fraction (about 84%) is less than that in the centre (where it is
      reaching values of over 96%). An important finding of this study thus is the fact
      that the bone tissue that is subjected to the highest temperatures is also
      subjected to high leftover monomer concentration. Furthermore the maximum bone
      temperature is reached relatively early, when monomer content in the neighbouring
      cement is still quite high.

PMID- 15519588
TI  - Contribution of the support limb in control of angular momentum after tripping.
AB  - Tripping over an obstacle can result in a fall when the forward angular momentum,
      obtained from impact with the obstacle, is not arrested. Angular momentum can be
      restrained by proper placement of the recovery limb, anteriorly of the body, but
      possibly also by a reaction in the contralateral support limb during push-off.
      The purpose of this study was to quantify the extent to which the support limb
      contributes to recovery after tripping by providing time and clearance for proper
      positioning of the recovery limb, and by restraining the angular momentum of the
      body during push-off. Twelve young adults were repeatedly tripped over an
      obstacle during mid-swing, while walking over a platform. Kinematics and ground
      reaction forces at the support limb were measured. Quantification of the angular
      momentum was based on calculation of the external moment, which equals the rate
      of change in the angular momentum of the body. Results showed that all subjects
      acquired a similar increase in angular momentum during foot-obstacle contact, on
      average 11.4 kg m2s(-1). In all subjects, the support limb played a role in
      recovery after tripping by providing time and clearance for proper positioning of
      the recovery limb, as indicated by body elevation (6%) and the increased forward
      pelvis displacement over recovery stride (43%). Almost all subjects were also
      able to restrain the forward angular momentum of the body during push-off by the
      support limb. Less angular momentum remained to be further accomplished by the
      recovery limb. Reductions in the quality of the support limb responses may be
      among the factors that increase the risk of falling in the elderly.

PMID- 15519589
TI  - A repeated sampling bone chamber methodology for the evaluation of tissue
      differentiation and bone adaptation around titanium implants under controlled
      mechanical conditions.
AB  - A repeated sampling bone chamber methodology was developed for the study of the
      influence of the mechanical environment on skeletal tissue differentiation and
      bone adaptation around titanium implants. Via perforations, bone grows into the
      implanted outer bone chamber, containing an inner bone chamber with a central
      test implant. An actuator--easily mounted on the outer bone chamber--allows a
      controlled mechanical stimulation of the test implant. After each experiment, the
      inner bone chamber--with its content--can be harvested and analysed. A new inner
      bone chamber with a central implant can be inserted consecutively in the outer
      bone chamber and a new experiment can start. Pilot studies led to a reliable
      surgical protocol and showed the applicability of the methodology, offering the
      possibility to study skeletal tissue differentiation and adaptation around
      implants under well-controlled mechanical conditions, and this protected from
      external loading. Repeated sampling of the bone chamber allows conducting several
      experiments within the same animal at the same site, thereby excluding subject-
      and site-dependent variability and reducing the amount of experimental animals.

PMID- 15519590
TI  - Ligament fibre recruitment at the human ankle joint complex in passive flexion.
AB  - Knowledge of ligament fibre recruitment at the human ankle joint complex is a
      fundamental prerequisite for analysing mobility and stability. Previous
      experimental and modelling studies have shown that ankle motion must be guided by
      fibres within the calcaneofibular and tibiocalcaneal ligaments, which remain
      approximately isometric during passive flexion. The purpose of this study was to
      identify these fibres. Three below-knee amputated specimens were analysed during
      passive flexion with combined radiostereometry for bone pose estimation and 3D
      digitisation for ligament attachment area identification. A procedure based on
      singular value decomposition enabled matching bone pose with digitised data and
      therefore reconstructing position in space of ligament attachment areas in each
      joint position. Eleven ordered fibres, connecting corresponding points on origin
      and insertion curves, were modelled for each of the following ligaments:
      posterior talofibular, calcaneofibular, anterior talofibular, posterior
      tibiotalar, tibiocalcaneal, and anterior tibiotalar. The measured changes in
      length for the ligament fibres revealed patterns of tightening and slackening.
      The most anterior fibre of the calcaneofibular and the medio-anterior fibre of
      the tibiocalcaneal ligament exhibited the most isometric behaviour, as well as
      the most posterior fibre of the anterior talofibular ligament. Fibres within the
      calcaneofibular ligament remain parallel in the transverse plane, while those
      within the tibiocalcaneal ligament become almost parallel in joint neutral
      position. For both these ligaments, fibres maintain their relative inclination in
      the sagittal plane throughout the passive flexion range. The observed significant
      change in both shape and orientation of the ankle ligaments suggest that this
      knowledge is fundamental for future mechanical analysis of their response to
      external forces.

PMID- 15519591
TI  - Analysis of the human and ape foot during bipedal standing with implications for
      the evolution of the foot.
AB  - The ratio of the power arm (the distance from the heel to the talocrural joint)
      to the load arm (that from the talocrural joint to the distal head of the
      metatarsals), or RPL, differs markedly between the human and ape foot. The arches
      are relatively higher in the human foot in comparison with those in apes. This
      study evaluates the effect of these two differences on biomechanical
      effectiveness during bipedal standing, estimating the forces acting across the
      talocrural and tarsometatarsal joints, and attempts to identify which type of
      foot is optimal for bipedal standing. A simple model of the foot musculoskeletal
      system was built to represent the geometric and force relationships in the foot
      during bipedal standing, and measurements for a variety of human and ape feet
      applied. The results show that: (1) an RPL of around 40% (as is the case in the
      human foot) minimizes required muscle force at the talocrural joint; (2) the
      presence of an high arch in the human foot reduces forces in the plantar
      musculature and aponeurosis; and (3) the human foot has a lower total of force in
      joints and muscles than do the ape feet. These results indicate that the
      proportions of the human foot, and the height of the medial arch are indeed
      better optimized for bipedal standing than those of apes, further suggesting that
      their current state is to some extent the product of positive selection for
      enhanced bipedal standing during the evolution of the foot.

PMID- 15519592
TI  - A numerical and experimental study of compliance and collapsibility of preterm
      lamb tracheae.
AB  - Knowledge of the mechanical behaviour of immature tracheae is crucial in order to
      understand the effects exerted on central airways by ventilatory treatments,
      particularly of Total Liquid Ventilation. In this study, a combined experimental
      and computational approach was adopted to investigate the compliance and
      particularly collapsibility of preterm lamb tracheae in the range of pressure
      likely applied during Total Liquid Ventilation (-30 to 30 cmH2O). Tracheal
      samples of preterm lambs (n = 5; gestational age 120-130 days) were tested by
      altering transmural pressure from -30 to 30 cmH2O. Inflation (Si) and collapsing
      (Sc) compliance values were calculated in the ranges 0 to 10 cmH2O and -10 to 0
      cmH2O, respectively. During the tests, an asymmetric behaviour of the DeltaV/V0
      vs. P curves at positive and negative pressure was observed, with mean Si = 0.013
      cmH2O(-1) and Sc = 0.053 cmH2O(-1). A different deformed configuration of the
      sample regions was observed, depending on the posterior shape of cartilaginous
      ring. A three-dimensional finite-element structural model of a single tracheal
      ring, based on histology measurements of the tested samples was developed. The
      model was parameterised in order to represent rings belonging to three different
      tracheal regions (craniad, median, caudal) and numerical analyses replicating the
      collapse test conditions were performed to evaluate the ring collapsibility at
      pressures between 0 and -30 cmH2O. Simulation results were compared to
      experimental data to verify the model's reliability. The best model predictions
      occurred at pressures -30 to -10 cmH2O. In this range, a model composed of median
      rings best interpreted the experimental data, with a maximum error of 2.7%; a
      model composed of an equal combination of all rings yielded an error of 12.6%.

PMID- 15519593
TI  - A quasi-static three-dimensional, mathematical, three-body segment model of the
      canine knee.
AB  - A mathematical, three-dimensional, anatomically accurate model of the canine knee
      was created to determine the forces in the knee ligaments and the knee joint
      reaction forces during the stance phase of a slow walk. This quasi-static model
      considered both the tibio-femoral and patello-femoral articulations. The
      geometric and morphometric data of the hind limb were obtained from cadaver data.
      Muscle forces acting on the femur and the hip joint reaction force were
      determined by numerical optimization. Ligaments were modeled as non-linear
      springs. Ligament material properties were obtained from the literature
      pertaining to the human knee. The model consists of-28 non-linear algebraic
      equations describing equilibrium of the femur and the patella, and geometric
      constraints. This system of equations was solved by a non-linear least-squares
      method. Results are presented for a knee with an intact cranial cruciate ligament
      (CCL) and for a knee with a ruptured CCL. Forces predicted to occur in the CCL by
      analysis of the model were found to be very similar to reported results of CCL
      forces measured in vivo in goats.

PMID- 15519594
TI  - A time-dependent healing function for immediate loaded implants.
AB  - Current interest in immediate dental implant loading has grown due to a number of
      clinical advantages this treatment modality offers. To obtain a deeper insight
      into the changing mechanical properties during the healing phase, results from
      removal torque tests are used in a biomechanical model. The ultimate removal
      torques, which depend on healing time, are described by a time-dependent healing
      function. The bone behavior is modeled using an elastic law with damage. The
      evolution of damage is represented with an incremental equation with an initial
      damage value and two material parameters. The nonlinear relationship between the
      torque and the angle of rotation up to the ultimate torque can be calculated. By
      changing the elastic parameter in the elastic damage law, the remodeling process
      can be characterized. In a further step, the elastic parameters and the limits
      for shear stress from the biomechanical model for the removal torque will be used
      in an FE analysis in order to obtain information on the axial loading limits of a
      dental implant at different healing times.

PMID- 15519595
TI  - Quantification of human motion: gait analysis-benefits and limitations to its
      application to clinical problems.
AB  - The technology supporting the analysis of human motion has advanced dramatically.
      Past decades of locomotion research have provided us with significant knowledge
      about the accuracy of tests performed, the understanding of the process of human
      locomotion, and how clinical testing can be used to evaluate medical disorders
      and affect their treatment. Gait analysis is now recognized as clinically useful
      and financially reimbursable for some medical conditions. Yet, the routine
      clinical use of gait analysis has seen very limited growth. The issue of its
      clinical value is related to many factors, including the applicability of
      existing technology to addressing clinical problems; the limited use of such
      tests to address a wide variety of medical disorders; the manner in which gait
      laboratories are organized, tests are performed, and reports generated; and the
      clinical understanding and expectations of laboratory results. Clinical use is
      most hampered by the length of time and costs required for performing a study and
      interpreting it. A "gait" report is lengthy, its data are not well understood,
      and it includes a clinical interpretation, all of which do not occur with other
      clinical tests. Current biotechnology research is seeking to address these
      problems by creating techniques to capture data rapidly, accurately, and
      efficiently, and to interpret such data by an assortment of modeling,
      statistical, wave interpretation, and artificial intelligence methodologies. The
      success of such efforts rests on both our technical abilities and communication
      between engineers and clinicians.

PMID- 15519596
TI  - Evolutionary optimization for robust hierarchical computation of the rotation
      centres of kinematic chains from reduced ranges of motion the lower spine case.
AB  - A novel technique based on evolutionary optimization is proposed here to compute
      the average rotation centres (RCs) of ball joints linked into kinematic chains
      using 3D trajectories of the markers attached to the external surface of the
      corresponding articulated structures. The chain is hierarchically solved by
      iteratively minimizing the variance of the marker distances from the actual RC
      through an evolutional strategy method (ESM) from proximal to distal joints. In
      particular, the technique is compared to the non-rigid sphere-fitting method,
      recently proposed in literature and implemented through a closed-form solution
      (CFS), in conditions of random and systematic noise superimposed to the marker
      coordinates. Results from simulated motions showed that, in case of small range
      of motion (5 degrees , 10 degrees ) the performance of CFS is really unreliable
      whereas ESM provided satisfactory accuracy. Error propagation along the kinematic
      chain was found to be negligible. Also in the case of systematic errors, ESM
      provides an accuracy that is sensibly better than that of the CFS. As a case
      study, ESM was applied to the in vivo computation of the RCs of the vertebrae in
      the lower spine region using a specific marker protocol. A set of spine movements
      by a normal adult male, recorded by an optoelectronic motion capture system, were
      processed with the developed method. The variability of the estimated average RCs
      was small (few millimeters) in agreement with the literature data from cadaveric
      studies and X-ray imaging.

PMID- 15519597
TI  - Accuracy of non-differential GPS for the determination of speed over ground.
AB  - Accurate determination of speed is important in many studies of human and animal
      locomotion. Some global positioning system (GPS) receivers can data log
      instantaneous speed. The speed accuracy of these systems is, however, unclear
      with manufacturers reporting velocity accuracies of 0.1-0.2 ms(-1). This study
      set out to trial non-differential GPS as a means of determining speed under real
      life conditions. A bicycle was ridden around a running track and a custom-made
      bicycle speedometer was calibrated. Additional experiments were performed around
      circular tracks of known circumference and along a straight road. Instantaneous
      speed was determined simultaneously by the custom speedometer and a data logging
      helmet-mounted GPS receiver. GPS speed was compared to speedometer speed. The
      effect on speed accuracy of satellite number; changing satellite geometry,
      achieved through shielding the GPS antenna; speed; horizontal dilution of
      precision and cyclist position on a straight or a bend, was evaluated. The
      relative contribution of each variable to overall speed accuracy was determined
      by ANOVA. The speed determined by the GPS receiver was within 0.2 ms(-1) of the
      true speed measured for 45% of the values with a further 19% lying within 0.4 ms(
      1) (n = 5060). The accuracy of speed determination was preserved even when the
      positional data were degraded due to poor satellite number or geometry. GPS data
      loggers are therefore accurate for the determination of speed over-ground in
      biomechanical and energetic studies performed on relatively straight courses.
      Errors increase on circular paths, especially those with small radii of
      curvature, due to a tendency to underestimate speed.

PMID- 15519598
TI  - Numerical investigation of the non-Newtonian blood flow in a bifurcation model
      with a non-planar branch.
AB  - The non-Newtonian fluid flow in a bifurcation model with a non-planar daughter
      branch is investigated by using finite element method to solve the three
      dimensional Navier-Stokes equations coupled with a non-Newtonian constitutive
      model, in which the shear thinning behavior of the blood fluid is incorporated by
      the Carreau-Yasuda model. The objective of this study is to investigate the
      influence of the non-Newtonian property of fluid as well as of curvature and out
      of-plane geometry in the non-planar daughter vessel on wall shear stress (WSS)
      and flow phenomena. In the non-planar daughter vessel, the flows are typified by
      the skewing of the velocity profile towards the outer wall, creating a relatively
      low WSS at the inner wall. In the downstream of the bifurcation, the velocity
      profiles are shifted towards the flow divider. The low WSS is found at the inner
      walls of the curvature and the lateral walls of the bifurcation. Secondary flow
      patterns that swirl fluid from the inner wall of curvature to the outer wall in
      the middle of the vessel are also well documented for the curved and bifurcating
      vessels. The numerical results for the non-Newtonian fluid and the Newtonian
      fluid with original Reynolds number and the corresponding rescaled Reynolds
      number are presented. Significant difference between the non-Newtonian flow and
      the Newtonian flow is revealed; however, reasonable agreement between the non
      Newtonian flow and the rescaled Newtonian flow is found. Results of this study
      support the view that the non-planarity of blood vessels and the non-Newtonian
      properties of blood are an important factor in hemodynamics and may play a
      significant role in vascular biology and pathophysiology.

PMID- 15519599
TI  - The flow of bile in the human cystic duct.
AB  - Clinical studies suggest that the flow of bile in the biliary system may be a
      contributing factor in the pathogenesis of cholelithiasis, but little is known
      about its transport mechanism. This paper reports a numerical study of steady
      flow in human cystic duct models. In order to obtain parametric data on the
      effects of various anatomical features in the cystic duct, idealised models were
      constructed, first with staggered baffles in a channel to represent the valves of
      Heister and lumen. The qualitative consistency of these findings are validated by
      modelling two of the real cystic ducts obtained from operative cholangiograms.
      Three-dimensional (3D) models were also constructed to further verify the two
      dimensional (2D) results. It was found that the most significant geometric
      parameter affecting resistance is the baffle clearance (lumen size), followed by
      the number of baffles (number of folds in the valves of Heister), whilst the
      least significant ones are the curvature of the cystic duct and the angle between
      the neck and the gallbladder. The study presented here forms part of a larger
      project to understand the functions of the human cystic duct, especially the
      influence of its various anatomical structures on the resistance to bile flow, so
      that it may aid the assessment of the risk of stone formation in the gallbladder.

PMID- 15519600
TI  - An analysis of the complete strain field within Flexercell membranes.
AB  - The purpose of the current investigation was to use finite element analysis to
      quantify the complete strain field for the membranes of the Flexercell apparatus,
      a device extensively used to study the effects of mechanical loading on cultured
      cells. Four vacuum pressure simulations were run for the membrane for both the
      uniaxial and biaxial loading post, yielding the distribution of longitudinal
      (Exx) and transverse (Eyy) strain for the uniaxial post, and the radial (Err) and
      the circumferential (Ethetatheta) strain for the biaxial post. The discrete
      values of each strain were evaluated at the center of the loading post as well as
      the region off of the post. Experimental measurements were made for both types of
      loading posts in order to validate our simulations. The biaxial post simulation
      was found to provide a central circular region of equal and constant Err and
      Ethetatheta in the membrane on the post. Likewise, the uniaxial post simulation
      provided a definitive region of constant Exx for a central rectangular region on
      the post. For the uniaxial simulation, the region on the post resulted in small
      compressive Eyy, while the region off the post resulted in tensile Eyy. The
      biaxial simulation resulted in large tensile Err and Ethetatheta on the post,
      while the region off the post resulted in large Err and smaller Ethetatheta. Our
      simulations were reasonably consistent with the experimental measurements made
      for both types of loading posts. We believe that the results of this study will
      allow scientists to more accurately describe the response of cells to known
      strains on all portions of the membrane, thus increasing the range of known
      strain regions for investigation in the Flexercell apparatus.

PMID- 15519601
TI  - Understanding how an arm swing enhances performance in the vertical jump.
AB  - This investigation was conducted to examine the various theories that have been
      proposed to explain the enhancement of jumping performance when using an arm
      swing compared to when no arm swing is used. Twenty adult males were asked to
      perform a series of maximal vertical jumps while using an arm swing and again
      while holding their arms by their sides. Force, motion and electromyographical
      data were recorded during each performance. Participants jumped higher (0.086 m)
      in the arm swing compared to the no-arm swing condition and was due to increased
      height (28%) and velocity (72%) of the center of mass at take-off. The increased
      height at take-off was due to the elevation of the arm segments. The increased
      velocity of take-off stemmed from a complex series of events which allowed the
      arms to build up energy early in the jump and transfer it to the rest of the body
      during the later stages of the jump. This energy came from the shoulder and elbow
      joints as well as from extra work done at the hip. This energy was used to (i)
      increase the kinetic and potential energy of the arms at take-off, (ii) store and
      release energy from the muscles and tendons around the ankle, knee and hip joint,
      and (iii) 'pull' on the body through an upward force acting on the trunk at the
      shoulder. It was concluded that none of the prevailing theories exclusively
      explains the enhanced performance in the arm swing jump, but rather the enhanced
      performance is based on several mechanisms operating together.

PMID- 15519602
TI  - Oscillatory tension differentially modulates matrix metabolism and cytoskeletal
      organization in chondrocytes and fibrochondrocytes.
AB  - Several modes of mechanical stimulation, including compression, shear, and
      hydrostatic pressure, have been shown to modulate chondrocyte matrix synthesis,
      but the effects of mechanical tension have not been widely explored. Since
      articular cartilage is primarily loaded in compression, tension is not generally
      viewed as a major contributor to the stress state of healthy tissue. However,
      injury or attempted repair may cause tension to become more significant.
      Additionally, fibrocartilaginous tissues experience significant tensile stresses
      in their normal mechanical environment. In this study we investigated mechanical
      tension as a means to modulate matrix synthesis and cytoskeletal organization in
      bovine articular chondrocytes and meniscal fibrochondrocytes (MFCs) in a three
      dimensional fibrin construct culture system. Oscillatory tension was applied to
      constructs at 1.0 Hz and 0-10% displacement variation using a custom device. For
      nearly all conditions and both cell types, oscillatory tension inhibited matrix
      synthesis as indicated by 3H-proline and 35S-sulfate incorporation. Additionally,
      oscillatory tension significantly increased proliferation by chondrocytes but not
      MFCs. Confocal imaging revealed that all cells initially displayed a rounded
      morphology, but over time MFCs spontaneously developed a three-dimensional,
      stellate morphology with numerous projections containing organized cytoskeletal
      filaments. Interestingly, while unloaded chondrocytes remained rounded,
      chondrocytes subjected to oscillatory tension developed a similar stellate
      morphology. Both the biochemical and morphological results of this study have
      important implications for successfully developing cartilage and fibrocartilage
      tissue replacements and repair strategies.

PMID- 15519603
TI  - Distribution of nitroreductive activity toward nilutamide in rat.
AB  - Nilutamide is a pneumotoxic and hepatotoxic nitroaromatic (R-NO2) antiandrogen
      used in the treatment of prostate carcinoma in man. Previously, we established
      that in the rat lung, the drug is metabolized into the corresponding
      hydroxylamine (R-NHOH) and amine (R-NH2) derivatives. These results evidenced a
      cytosolic oxygen-sensitive (type II) nitroreductase activity in lung. In the
      present studies, we extended the characterization of nilutamide metabolism in
      liver, brain, kidney, heart, blood, intestine (small, cecum, and large, and their
      respective luminal contents) of male Sprague-Dawley rats. Subcellular fractions
      for all tissues (except blood) examined (postmitochondrial, cytosolic, and
      microsomal) were prepared by differential ultracentrifugation. Blood and
      intestinal contents were sonicated before investigation. Incubations were run in
      the presence or absence of O2 to assess type I and II nitroreductase activities.
      Organic extracts were analyzed by HPLC methods and results were expressed as
      pmoles of R-NH2 formed per milligram protein per minute. Four distinct
      nitroreductive activities were evidenced. Cytosolic and microsomal type II
      nitroreductase activities were detected in all tissue samples studied. Type I NR
      activity was not observed in any of the cytosols, but was detected in the small
      intestine, lung, kidney, and liver microsomes. Nilutamide was also reduced in the
      intestinal lumen, possibly by a bacterial type I nitroreductase. Highest
      activities were observed in cytosols and were oxygen sensitive. These results
      evidence and characterize previously unknown nitroreductive activities toward
      nilutamide in rat tissues that might provide some explanation to the side effects
      of nilutamide and other nitroaromatic compounds observed in human therapeutics.

PMID- 15519604
TI  - The combined antiandrogenic effects of five commonly used pesticides.
AB  - In this study, mixture effects of five dissimilarly acting pesticides were
      analyzed for antiandrogenic effects in vitro and in vivo. Deltamethrin,
      methiocarb, prochloraz, simazine, and tribenuron-methyl are all commonly used for
      agricultural and horticultural purposes. Concentration-response curves for the
      inhibition of R1881-induced transcriptional activity of the androgen receptor
      (AR) in vitro of each pesticide alone and in an equimolar mixture were obtained.
      The IC25 values for deltamethrin, methiocarb, prochloraz, and the mixture were
      5.8, 5.8, 3.5, and 7.5 microM, respectively. Simazine and tribenuron-methyl were
      ineffective. Applying the isobole method resulted in an isobole coefficient of
      0.94 at IC25 for the effect of the mixture, indicating additive effects of the
      compounds. Comparison of observed effects and effects calculated by assuming
      additivity also strongly indicated additive effects of the pesticides in vitro.
      In vivo, each of the five pesticides and a mixture of the pesticides were tested
      for antiandrogenic effects in castrated testosterone-treated Wistar rats. The
      mixture induced a significant change of weights of the levator
      ani/bulbocavernosus muscle and adrenal glands. Changes in gene expression in
      ventral prostates were observed as distinct effects on levels of ornithin
      decarboxylase (ODC) mRNA and effects on levels of prostate binding protein
      subunit C3 (PBP C3) mRNA. No pesticide-induced effect on the level of
      testosterone-repressed prostatic message 2 (TRPM-2) mRNA was observed, whereas
      flutamide increased TRPM-2 levels. In conclusion, the pesticides were found to
      act additively in vitro. In vivo, the organ weight changes indicated that the
      pesticides had an accumulating effect that was not observed for the individual
      pesticides. Several pesticide-induced gene expression changes were observed,
      indicating that these are either very sensitive antiandrogenic end-points or that
      these changes are induced by a pathway not related to AR.

PMID- 15519605
TI  - Paraquat induces oxidative stress and neuronal cell death; neuroprotection by
      water-soluble Coenzyme Q10.
AB  - Neuronal cell death induced by oxidative stress is correlated with numerous
      neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's
      disease (PD), and stroke. The causes of sporadic forms of age-related
      neurodegenerative diseases are still unknown. Recently, a correlation between
      paraquat exposure and neurodegenerative diseases has been observed. Paraquat, a
      nonselective herbicide, was once widely used in North America and is still
      routinely used in Taiwan. We have used differentiated Human Neuroblastoma (SHSY
      5Y) cells as an in vitro model to study the mechanism of cell death induced by
      paraquat. We observed that paraquat-induced oxidative stress in differentiated
      SHSY-5Y cells as indicated by an increase in the production of cellular reactive
      oxygen species (ROS). Furthermore, apoptosis was evident as indicated by cellular
      and nuclear morphology and DNA fragmentation. Interestingly, pretreatment of SHSY
      5Y cells with water-soluble Coenzyme Q10 (CoQ10) before paraquat exposure
      inhibited ROS generation. Pretreatment with CoQ10 also significantly reduced the
      number of apoptotic cells and DNA fragmentation. We also analyzed the effect of
      paraquat and CoQ10 on isolated mitochondria. Our results indicated that treatment
      with paraquat induced the generation of ROS from isolated mitochondria and
      depolarization of the inner mitochondrial membrane. Pretreatment with CoQ10 was
      able to inhibit ROS generation from isolated mitochondria as well as the collapse
      of mitochondrial membrane potential. Our results indicate that water-soluble
      CoQ10 can prevent oxidative stress and neuronal damage induced by paraquat and
      therefore, can be used for the prevention and therapy of neurodegenerative
      diseases caused by environmental toxins.

PMID- 15519606
TI  - Arsenic exposure exacerbates atherosclerotic plaque formation and increases
      nitrotyrosine and leukotriene biosynthesis.
AB  - A correlation between arsenic and cardiovascular disease (CVD) has been
      established through epidemiological studies, although the mechanisms are unknown.
      Using a mouse model that develops atherosclerotic lesions on a normal chow diet,
      we have confirmed a connection between long-term arsenic intake and CVD. Our
      results reveal a significant increase in the degree of atherosclerotic plaque
      stenosis within the innominate artery of ApoE-/-/LDLr-/- mice treated with 10 ppm
      sodium arsenite (133 microM) in drinking water for 18 weeks compared to controls.
      Immunohistochemistry shows nitrotyrosine formation, a marker of reactive nitrogen
      species generation, is significantly higher within the atherosclerotic plaque of
      arsenic-treated mice. In addition, there is a significant increase in the 5
      lipoxygenase (5-LO) product, leukotriene E4 (LTE4), in the serum of arsenic
      treated mice. This is supported by induction of the 5-LO protein and subsequent
      increases in LTE4 synthesis in bovine aortic endothelial cells. This increase in
      LTE4 is partially inhibited by inhibitors of nitric oxide synthase, suggesting a
      link between reactive nitrogen species and arsenic-induced inflammation.
      Furthermore, there is a significant increase in prostacyclin (PGI2) in the serum
      of arsenic-treated mice. We conclude that changes in specific inflammatory
      mediators such as LTE4 and PGI2 are related to arsenic-induced atherosclerosis.
      In addition, amplified synthesis of reactive species such as peroxynitrite
      results in increased protein nitration in response to arsenic exposure. This
      finding is consistent with the pathology seen in human atherosclerotic plaques.

PMID- 15519607
TI  - Benzo[a]pyrene-induced immunotoxicity in Japanese medaka (Oryzias latipes):
      relationship between lymphoid CYP1A activity and humoral immune suppression.
AB  - Exposure to the environmental contaminant benzo[a]pyrene (BaP) results in
      suppression of immune function in both mammalian and fish species. This
      laboratory has previously demonstrated that a single intraperitoneal (IP)
      injection of BaP reduced lymphocyte proliferation, phagocyte-mediated superoxide
      generation, and antibody-forming cell (AFC) numbers in Japanese medaka (Oryzias
      latipes). The objective of the current study was to determine the role of BaP
      metabolism in the observed immunosuppression. Results from rodent studies have
      suggested that BaP elicits its immunotoxic effects via upregulation of cytochrome
      P4501A1 (CYP1A1) and the subsequent production of immunosuppressive BaP
      metabolites. In this study, exposure of medaka to 200 microg BaP/g BW
      significantly induced CYP1A expression or activity within lymphoid tissue 48 h
      post-IP injection; induction was observed specifically within distinct
      subpopulations of kidney mononuclear cells. Concurrent injection of fish with BaP
      and the CYP1A1 inhibitors alpha-naphthoflavone (ANF) or dehydroepiandrosterone
      (DHEA) resulted in inhibition of renal EROD activity and amelioration of BaP
      induced suppression of medaka AFC numbers. Results of this study suggest that (1)
      BaP-induced suppression of medaka humoral immunity relies upon the CYP1A
      catalyzed production of immunotoxic BaP metabolites and (2) BaP metabolites may
      be created in situ, directly by specific cells within kidney lymphoid tissue.
      Thus, apparently, mechanisms involved in BaP-induced immunosuppression have been
      phylogenetically conserved from fish to mammals.

PMID- 15519608
TI  - Increased vulnerability of neonatal rats and mice to 1-nitronaphthalene-induced
      pulmonary injury.
AB  - The postnatal period of lung development is a critical window of susceptibility
      to environmental toxicants, including polyaromatic hydrocarbons (PAHs) and
      furans. To determine whether the increased susceptibility of neonatal lung injury
      due to environmental toxicants is a universal response across species and also
      applies to nitrated compounds, adult and 7-day-old male mice and rats were given
      a single intraperitoneal dose (0, 12.5, 25, 50, or 100 mg/kg) of 1
      nitronaphthalene and killed 24 h later. Exposure to 1-nitronaphthalene, a nitro
      polyaromatic hydrocarbon, results in pulmonary lesions in both adult rats and
      mice, although the severity of the injury is species-specific (greater in rats
      than in mice). Pulmonary lesions, as assessed by quantitative histopathology,
      included dose-dependent vacuolization and exfoliation of both ciliated and
      nonciliated airway epithelial cells throughout the airway tree in both rats and
      mice. In both species, the 7-day-old animals were more susceptible to injury by 1
      nitronaphthalene than adult animals. In contrast to adult response, neonatal mice
      were more susceptible to 1-nitronaphthalene-induced pulmonary injury than
      neonatal rats. This indicates that neonatal susceptibility to environmental
      pollutant-induced lung injury cannot be reliably predicted based on adult
      susceptibility.

PMID- 15519609
TI  - Toxicology of antisense therapeutics.
AB  - Targeting unique mRNA molecules using antisense approaches, based on sequence
      specificity of double-stranded nucleic acid interactions should, in theory, allow
      for design of drugs with high specificity for intended targets. Antisense-induced
      degradation or inhibition of translation of a target mRNA is potentially capable
      of inhibiting the expression of any target protein. In fact, a large number of
      proteins of widely varied character have been successfully downregulated using an
      assortment of antisense-based approaches. The most prevalent approach has been to
      use antisense oligonucleotides (ASOs), which have progressed through the
      preclinical development stages including pharmacokinetics and toxicological
      studies. A small number of ASOs are currently in human clinical trials. These
      trials have highlighted several toxicities that are attributable to the chemical
      structure of the ASOs, and not to the particular ASO or target mRNA sequence.
      These include mild thrombocytopenia and hyperglycemia, activation of the
      complement and coagulation cascades, and hypotension. Dose-limiting toxicities
      have been related to hepatocellular degeneration leading to decreased levels of
      albumin and cholesterol. Despite these toxicities, which are generally mild and
      readily treatable with available standard medications, the clinical trials have
      clearly shown that ASOs can be safely administered to patients. Alternative
      chemistries of ASOs are also being pursued by many investigators to improve
      specificity and antisense efficacy and to reduce toxicity. In the design of ASOs
      for anticancer therapeutics in particular, the goal is often to enhance the
      cytotoxicity of traditional drugs toward cancer cells or to reduce the toxicity
      to normal cells to improve the therapeutic index of existing clinically relevant
      cancer chemotherapy drugs. We predict that use of antisense ASOs in combination
      with small molecule therapeutics against the target protein encoded by the
      antisense-targeted mRNA, or an alternate target in the same or a connected
      biological pathway, will likely be the most beneficial application of this
      emerging class of therapeutic agent.

PMID- 15519610
TI  - Mexico, 2004: global health needs a new research agenda.

PMID- 15519611
TI  - Zero tolerance for domestic violence.

PMID- 15519612
TI  - Integrating the management of childhood illness.

PMID- 15519613
TI  - The effect of health care on population health.

PMID- 15519614
TI  - Applying the right standards to improve hospital performance in Africa.

PMID- 15519615
TI  - Avoiding HIV and dying of syphilis.

PMID- 15519616
TI  - Injury surveillance is key to preventing injuries.

PMID- 15519617
TI  - The meeting that did not happen: Cairo, 10 years on.

PMID- 15519618
TI  - When will health care pass the orange-wire test?

PMID- 15519619
TI  - Health and hunger in Zimbabwe.

PMID- 15519620
TI  - Should rosuvastatin be withdrawn from the market?

PMID- 15519621
TI  - Should rosuvastatin be withdrawn from the market?

PMID- 15519624
TI  - Should rosuvastatin be withdrawn from the market?

PMID- 15519625
TI  - Discontinuation of Mysoline: lessons to be learned.

PMID- 15519627
TI  - The Tailor of Gloucester: a jacket for the Marfan's aorta.

PMID- 15519628
TI  - Effectiveness and cost of facility-based Integrated Management of Childhood
      Illness (IMCI) in Tanzania.
AB  - BACKGROUND: The Integrated Management of Childhood Illness (IMCI) strategy is
      designed to address major causes of child mortality at the levels of community,
      health facility, and health system. We assessed the effectiveness of facility
      based IMCI in rural Tanzania. METHODS: We compared two districts with facility
      based IMCI and two neighbouring comparison districts without IMCI, from 1997 to
      2002, in a non-randomised study. We assessed quality of case-management for
      children's illness, drug and vaccine availability, and supervision involving case
      management, through a health-facility survey in 2000. Household surveys were used
      to assess child-health indicators in 1999 and 2002. Survival of children was
      tracked through demographic surveillance over a predefined 2-year period from mid
      2000. Further information on contextual factors was gathered through interviews
      and record review. The economic cost of health care for children in IMCI and
      comparison districts was estimated through interviews and record review at
      national, district, facility, and household levels. FINDINGS: During the IMCI
      phase-in period, mortality rates in children under 5 years old were almost
      identical in IMCI and comparison districts. Over the next 2 years, the mortality
      rate was 13% lower in IMCI than in comparison districts (95% CI -7 to 30 or 5 to
      21, depending on how adjustment is made for district-level clustering), with a
      rate difference of 3.8 fewer deaths per 1000 child-years. Contextual factors,
      such as use of mosquito nets, all favoured the comparison districts. Costs of
      children's health care with IMCI were similar to or lower than those for case
      management without IMCI. INTERPRETATION: Our findings indicate that facility
      based IMCI is good value for money, and support widespread implementation in the
      context of health-sector reform, basket funding, good facility access, and high
      utilisation of health facilities.

PMID- 15519630
TI  - Human resources and health outcomes: cross-country econometric study.
AB  - BACKGROUND: Only a few studies have investigated the link between human resources
      for health and health outcomes, and they arrive at different conclusions. We
      tested the strength and significance of density of human resources for health
      with improved methods and a new WHO dataset. METHODS: We did cross-country
      multiple regression analyses with maternal mortality rate, infant mortality rate,
      and under-five mortality rate as dependent variables. Aggregate density of human
      resources for health was an independent variable in one set of regressions;
      doctor and nurse densities separately were used in another set. We controlled for
      the effects of income, female adult literacy, and absolute income poverty.
      FINDINGS: Density of human resources for health is significant in accounting for
      maternal mortality rate, infant mortality rate, and under-five mortality rate
      (with elasticities ranging from -0.474 to -0.212, all p values < or = 0.0036).
      The elasticities of the three mortality rates with respect to doctor density
      ranged from -0.386 to -0.174 (all p values < or = 0.0029). Nurse density was not
      associated except in the maternal mortality rate regression without income
      poverty (p=0.0443). INTERPRETATION: In addition to other determinants, the
      density of human resources for health is important in accounting for the
      variation in rates of maternal mortality, infant mortality, and under-five
      mortality across countries. The effect of this density in reducing maternal
      mortality is greater than in reducing child mortality, possibly because qualified
      medical personnel can better address the illnesses that put mothers at risk.
      Investment in human resources for health must be considered as part of a strategy
      to achieve the Millennium Development Goals of improving maternal health and
      reducing child mortality.

PMID- 15519629
TI  - Integrated Management of Childhood Illness (IMCI) in Bangladesh: early findings
      from a cluster-randomised study.
AB  - BACKGROUND: We report the preliminary findings from a continuing cluster
      randomised evaluation of the Integrated Management of Childhood Illness (IMCI)
      strategy in Bangladesh. METHODS: 20 first-level outpatient facilities in the
      Matlab sub-district and their catchment areas were randomised to either IMCI or
      standard care. Surveys were done in households and in health facilities at
      baseline and were repeated about 2 years after implementation. Data on use of
      health facilities were recorded. IMCI implementation included health worker
      training, health systems support, and community level activities guided by
      formative research. FINDINGS: 94% of health workers in the intervention
      facilities were trained in IMCI. Health systems supports were generally
      available, but implementation of the community activities was slow. The mean
      index of correct treatment for sick children was 54 in IMCI facilities compared
      with 9 in comparison facilities (range 0-100). Use of the IMCI facilities
      increased from 0.6 visits per child per year at baseline to 1.9 visits per child
      per year about 21 months after IMCI introduction. 19% of sick children in the
      IMCI area were taken to a health worker compared with 9% in the non-IMCI area.
      INTERPRETATION: 2 years into the assessment, the results show improvements in the
      quality of care in health facilities, increases in use of facilities, and gains
      in the proportion of sick children taken to an appropriate health care provider.
      These findings are being used to strengthen child health care nationwide. They
      suggest that low levels of use of health facilities could be improved by
      investing in quality of care and health systems support.

PMID- 15519631
TI  - Pneumatocoele and conjunctivitis in a newborn.

PMID- 15519632
TI  - HIV and hepatitis C virus RNA in seronegative organ and tissue donors.
AB  - The objective of our study was to determine whether nucleic acid testing could
      detect HIV RNA or hepatitis C virus (HCV) RNA in a large series of seronegative
      organ and tissue donors, and whether this technique should be routinely used to
      improve viral safety of grafts. We studied 2236 organ donors, 636 tissue donors,
      and 177 cornea donors. We identified five HCV RNA-positive donors in 2119 HCV
      seronegative organ donors, and one HCV RNA-positive donor in 631 HCV-seronegative
      tissue donors. No HIV-seronegative, HIV RNA-positive donor was identified. Our
      data suggest that routine nucleic acid testing of organ and tissue donors might
      increase viral safety in transplantation.

PMID- 15519633
TI  - Seasonality of tuberculosis in India: is it real and what does it tell us?
AB  - India has a third of the world's tuberculosis cases. Large-scale expansion of a
      national programme in 1998 has allowed for population-based analyses of data from
      tuberculosis registries. We assessed seasonal trends using quarterly reports from
      districts with stable tuberculosis control programmes (population 115 million).
      In northern India, tuberculosis diagnoses peaked between April and June, and
      reached a nadir between October and December, whereas no seasonality was reported
      in the south. Overall, rates of new smear-positive tuberculosis cases were 57 per
      100000 population in peak seasons versus 46 per 100000 in trough seasons. General
      health-seeking behaviour artifact was ruled out. Seasonality was highest in
      paediatric cases, suggesting variation in recent transmission.

PMID- 15519634
TI  - Use of research to inform public policymaking.
AB  - To improve health and reduce health inequalities, public policymakers need to
      find the best solutions to the most burdensome health problems, the best ways to
      fit these solutions into complex and often overstretched and underresourced
      health systems, and the best ways to bring about the desired changes in health
      systems. Systematic reviews can inform public policymaking by providing research
      based answers to these questions. Public policymakers can encourage more informed
      policymaking by asking to see systematic reviews on priority issues,
      commissioning reviews when none exists, and placing more value on such work in
      their deliberations and in their interactions with stakeholders. Donors and
      international agencies can encourage more informed public policymaking by
      supporting national and regional efforts to undertake reviews and assess their
      local applicability, and by supporting regional or worldwide efforts to
      coordinate review and assessment processes.

PMID- 15519635
TI  - Delivery of paediatric care at the first-referral level in Kenya.
AB  - We aimed to investigate provision of paediatric care in government district
      hospitals in Kenya. We surveyed 14 first-referral level hospitals from seven of
      Kenya's eight provinces and obtained data for workload, outcome of admission,
      infrastructure, and resources and the views of hospital staff and caretakers of
      admitted children. Paediatric admission rates varied almost ten-fold. Basic anti
      infective drugs, clinical supplies, and laboratory tests were available in at
      least 12 hospitals, although these might be charged for on discharge. In at least
      11 hospitals, antistaphylococcal drugs, appropriate treatment for malnutrition,
      newborn feeds, and measurement of bilirubin were rarely or never available. Staff
      highlighted infrastructure and human and consumable resources as problems.
      However, a strong sense of commitment, support for the work of the hospital, and
      a desire for improvement were expressed. Caretakers' views were generally
      positive, although dissatisfaction with the physical environment in which care
      took place was common. The capacity of the district hospital in Kenya needs
      strengthening by comprehensive policies that address real needs if current or new
      interventions and services at this level of care are to enhance child survival.

PMID- 15519636
TI  - Pushing the international health research agenda towards equity and
      effectiveness.

PMID- 15519637
TI  - Dying for economic growth? Evidence of a flawed economic policy in Uganda.

PMID- 15519638
TI  - The man with "milk-shake" urine.

PMID- 15519640
TI  - Immunological tolerance and liver transplantation.

PMID- 15519641
TI  - Isoflurane pretreatment lowers portal venous resistance by increasing hepatic
      heme oxygenase activity in the rat liver in vivo.
AB  - BACKGROUND/AIMS: The heme oxygenase (HO) system contributes to the maintenance of
      hepatic perfusion and integrity. It was the objective of this study to determine
      the influence of isoflurane (ISO) on hepatic HO-1 induction and its impact on
      hepatic hemodynamics. METHODS: Rats were pretreated with or without ISO for 5h.
      After hemodynamic measurements by pressure-, laser doppler-, and ultrasound based
      techniques, the liver was harvested. HO-1 was analyzed by an HO activity assay,
      Northern- and Western blotting. RESULTS: ISO pretreatment induced hepatic HO-1
      mRNA and protein resulting in an increase of HO activity. No effect on hsp-27,
      hsp-70 and hsp-90 mRNA could be observed. ISO lowered portal resistance. HO
      inhibition by tin protoporphyrine IX increased portal resistance in ISO
      pretreated animals up to control levels. This was associated with an increase in
      portal pressure and a reduction of portal flow. Microvascular flux was also
      impaired after HO blockade and ISO. However, hepatic arterial and systemic
      hemodynamics remained unchanged, indicating a specific effect within the portal
      vascular bed. CONCLUSIONS: ISO pretreatment induces hepatic HO-1 mRNA and protein
      followed by an increase in HO activity, thereby reducing portal resistance. These
      findings indicate a beneficial effect of ISO on hepatic hemodynamics in vivo.

PMID- 15519642
TI  - Patterns of transgene expression and viral clearance from the transplanted liver
      following ex vivo adenovirus-mediated gene transfer.
AB  - BACKGROUND/AIMS: In the rat liver transplant model, the liver graft can be
      transduced ex vivo by adenovirus encoding CTLA-4Ig (AdCTLA-4Ig) to achieve high
      level of immunosuppression in the liver after transplantation. To characterize
      the pattern of transgene expression following ex vivo gene transfer to the liver
      and examine whether immunosuppression would promote adenovirus persistence, we
      followed the life span of vector DNA and transgene expression in the transplanted
      liver. METHODS: Rat liver grafts were perfused ex vivo with adenovirus carrying
      the reporter gene beta-galactosidase (AdlacZ). The period of transgene expression
      was assessed at predetermined intervals after transplantation into syngeneic,
      allogeneic or nude (athymic) recipients. Clearance of vector DNA was assessed by
      PCR analysis of liver DNA after transplantation. RESULTS: Graft transduction with
      AdCTLA-4Ig or systemic cyclosporine treatment effectively abrogated the
      alloimmune response but did not result in sustained lacZ expression. The course
      of viral DNA clearance from the liver was also unaffected by immunosuppression as
      was the implied nucleolytic cleavage of viral DNA. CONCLUSIONS: In the transplant
      setting, local expression of CTLA-4Ig or systemic immunosuppression does not
      solve the problem of viral clearance from the liver. Non-adaptive immune
      mechanisms may have a significant role in the host response to adenovirus after
      liver transplantation.

PMID- 15519643
TI  - Polyunsaturated fatty acid deficiency reverses effects of alcohol on
      mitochondrial energy metabolism.
AB  - BACKGROUND/AIMS: Polyunsaturated fatty acids (PUFA) deficiency is common in
      patients with alcoholic liver disease. The suitability of reversing such
      deficiency remains controversial. The aim was to investigate the role played by
      PUFA deficiency in the occurrence of alcohol-related mitochondrial dysfunction.
      METHODS: Wistar rats were fed either a control diet with or without alcohol
      (control and ethanol groups) or a PUFA deficient diet with or without alcohol
      (PUFA deficient and PUFA deficient+ethanol groups). After 6 weeks, liver
      mitochondria were isolated for energetic studies and fatty acid analysis.
      RESULTS: Mitochondria from ethanol fed rats showed a dramatic decrease in oxygen
      consumption rates and in cytochrome oxidase activity. PUFA deficiency showed an
      opposite picture. PUFA deficient+ethanol group roughly reach control values,
      regarding cytochrome oxidase activity and respiratory rates. The relationship
      between ATP synthesis and respiratory rate was shifted to the left in ethanol
      group and to the right in PUFA-deficient group. The plots of control and PUFA
      deficient+ethanol groups were overlapping. Phospholipid arachidonic over linoleic
      ratio closely correlated to cytochrome oxidase and oxygen uptake. CONCLUSIONS:
      PUFA deficiency reverses alcohol-related mitochondrial dysfunction via an
      increase in phospholipid arachidonic over linoleic ratio, which raises cytochrome
      oxidase activity. Such deficiency may be an adaptive mechanism.

PMID- 15519644
TI  - Pirfenidone inhibits the induction of iNOS stimulated by interleukin-1beta at a
      step of NF-kappaB DNA binding in hepatocytes.
AB  - BACKGROUND/AIMS: Pirfenidone has antiinflammatory effects in animals with
      endotoxemia. We reported that pirfenidone inhibits the enhancement of
      inflammatory cytokines and inducible nitric oxide synthase (iNOS) in liver of
      endotoxin-treated rats, leading to the prevention of hepatic injury. However, the
      mechanisms involved in suppression of these gene inductions are obscure. Studies
      were performed to investigate whether pirfenidone directly influences iNOS
      induction in hepatocytes. METHODS: Cultured hepatocytes were treated with
      interleukin-1beta (IL-1beta) in the presence and absence of pirfenidone, and iNOS
      induction and its signal including NF-kappaB were analyzed. RESULTS: Pirfenidone
      inhibited the induction of iNOS mRNA and protein, resulting in the decrease of
      nitric oxide production. Gel shift assay demonstrated that pirfenidone inhibited
      the activation of NF-kappaB. Consistent with this observation, transfection
      experiments revealed that pirfenidone decreased transcriptional activation of
      iNOS gene promoter. In contrast, pirfenidone had no effect on the degradation of
      IkappaB, and could not prevent nuclear translocation of p50/p65. Finally,
      pirfenidone inhibited the activation of Akt and up-regulation of IL-1 receptor
      stimulated by IL-1beta. CONCLUSIONS: Results indicate that pirfenidone inhibits
      the induction of iNOS gene expression at a step of NF-kappaB DNA binding, but not
      its nuclear translocation, partly through the inhibition of IL-1 receptor
      induction in hepatocytes.

PMID- 15519645
TI  - Mature hepatocytes are the source of small hepatocyte-like progenitor cells in
      the retrorsine model of liver injury.
AB  - BACKGROUND/AIMS: Mature hepatocytes divide to restore liver mass after injury.
      However, when hepatocyte division is impaired by retrorsine poisoning,
      regeneration proceeds from another cell type: the small hepatocyte-like
      progenitor cells (SHPCs). Our aim was to test whether SHPCs could originate from
      mature hepatocytes. METHODS: Mature hepatocytes were genetically labeled using
      retroviral vectors harboring the beta-galactosidase gene. After labeling,
      retrorsine was administered to rats followed by a partial hepatectomy to trigger
      regeneration. A liver biopsy was performed one month after surgery and rats were
      sacrificed one month later. RESULTS: We observed the proliferation of small
      hepatocytes arranged in clusters in liver biopsies. These cells expressed Ki67
      antigen and displayed a high mitotic index. At sacrifice, regeneration was
      completed and clusters had merged. A significant proportion of clusters also
      expressed beta-galactosidase demonstrating their origin from labeled mature
      hepatocytes. Finally, the overall proportion of beta-galactosidase positive cells
      was identical at the time of hepatectomy as well as in liver biopsy and at
      sacrifice. CONCLUSIONS: The constant proportion of beta-galactosidase positive
      cells during the regeneration process demonstrates that mature hepatocytes are
      randomly recruited to proliferate and compensate parenchyma loss in this model.
      Furthermore, mature hepatocytes are the source of SHPC after retrorsine injury.

PMID- 15519646
TI  - Genetic polymorphisms of ADH2, ADH3, CYP4502E1 Dra-I and Pst-I, and ALDH2 in
      Spanish men: lack of association with alcoholism and alcoholic liver disease.
AB  - BACKGROUND/AIMS: The relationship between polymorphisms at the alcohol
      dehydrogenase 2 (ADH(2)), ADH(3), CYP(450)2E1 and aldehyde dehydrogenase 2
      (ALDH(2)) loci and the individual predisposition to alcoholism and alcoholic
      liver disease in Caucasians is controversial. METHODS: We determined the
      genotypes of ADH(2), ADH(3), CYP(450)2E1 (Pst-I and Dra-I) and ALDH(2) in 519
      male Spaniards: 264 alcoholic subjects (47 without liver disease, 118 with non
      cirrhotic liver disease and 99 with cirrhosis) and 255 non-alcoholic subjects (64
      healthy controls, 110 with non-cirrhotic non-alcoholic liver disease and 81 with
      cirrhosis unrelated to alcohol). Genotyping was performed using PCR-RFLP methods
      on white cell DNA. RESULTS: The distribution of the allelic variants (allele *1
      and allele *2) in the whole subjects analyzed was: ADH(2) 93.1% and 6.9%; ADH(3)
      55.7 and 44.3%; CYP(450)2E1 Dra-I 11.2 and 88.8%; CYP(450)2E1 Pst-I 96.2 and 3.8%
      and ALDH2 100 and 0%, respectively. No differences were observed in the allelic
      distributions of the alcoholic and non-alcoholic subjects for the loci examined.
      Allele distribution in alcoholics with no liver disease, with alcoholic steatosis
      or hepatitis, and with cirrhosis was also similar. CONCLUSIONS: ADH(2), ADH(3),
      and CYP(450)2E1 Pst-I and Dra-I genetic variations are not related to alcoholism
      or susceptibility to alcoholic liver disease in our male population. ALDH(2)
      locus is monomorphic.

PMID- 15519647
TI  - Silent non-alcoholic fatty liver disease-a clinical-histological study.
AB  - BACKGROUND/AIMS: We studied the prevalence of non-alcoholic fatty liver disease
      and non-alcoholic-steatohepatitis in patients with metabolic-syndrome but normal
      liver enzymes. The histological findings of patients with normal liver enzymes
      and non-alcoholic-steatohepatitis were compared with those of a control-group
      with persistently abnormal liver enzymes. METHODS: Patients presenting with
      normal liver enzymes were enrolled in the study and underwent liver biopsy.
      Prevalence of non-alcoholic-steatohepatitis and risk factors for fibrosis and
      cirrhosis were evaluated. Data from a control-group with non-alcoholic
      steatohepatitis and abnormal liver enzymes were used to compare the histological
      findings. RESULTS: Fifty-eight of the 80 patients enrolled had varying degrees of
      non-alcoholic steatohepatitis, of these 26 had fibrosis and 8 silent cirrhosis.
      The association of metabolic-syndrome, female-sex, a long-history of obesity and
      body mass index>45 were considered to be independent risk-factors for fibrosis.
      Comparing the histological findings of cases and controls we found a similar
      severity of steatosis and fibrosis, with a greater prevalence of ballooning
      degeneration and glycogenated-nuclei rather than lobular-inflammation.
      CONCLUSIONS: In the subjects selected according to our criteria, liver enzyme
      levels could not be used as surrogate markers of non-alcoholic-steatohepatitis.
      Histological hallmarks of patients with metabolic-syndrome, normal liver enzymes
      and non-alcoholic-steatohepatitis consist to a lesser degree of lobular
      inflammation and a more severe ballooning and glycogenated-nuclei.

PMID- 15519648
TI  - The H1069Q mutation in ATP7B is associated with late and neurologic presentation
      in Wilson disease: results of a meta-analysis.
AB  - BACKGROUND AND AIMS: Wilson disease is an hereditary disorder of copper
      metabolism, caused by mutations in the ATP7B gene, and leading to hepatic or
      neurologic disease. We examined whether H1069Q, the most common ATP7B mutation,
      is associated with a specific phenotype. METHODS: Genotyping results in 70 Dutch
      patients were related to clinical presentation. Subsequently a meta-analysis for
      genotype-phenotype correlation was performed on all patients available from
      literature, combined with the current Dutch group, a total of 577 patients.
      RESULTS: The Dutch patients homozygous or heterozygous for the H1069Q mutation
      presented more frequently with neurologic disease (63% and 43% vs. 15%), and at a
      later age (20.9 and 15.9 vs. 12.6 years) than patients without the H1069Q
      mutation. In the meta-analysis the odds-ratio for neurologic presentation in
      homozygous or heterozygous H1069Q vs. non-H1069Q patients was 3.50 (95% CI 2.01
      6.09) and 2.13 (95% CI 1.18-3.83), respectively. Age at presentation was 21.1,
      19.2 and 16.5 years, respectively, corresponding to a weighted mean difference
      (WMD) of 4.41 (95% CI 1.56-7.26) for homozygous H1069Q vs. heterozygous patients
      and 6.68 (95% CI 4.33-9.38) for homozygous H1069Q vs. non-H1069Q patients.
      CONCLUSIONS: Our results indicate that the H1069Q mutation is associated with a
      late and neurologic presentation.

PMID- 15519649
TI  - Heme oxygenase-1 protects human hepatocytes in vitro against warm and cold
      hypoxia.
AB  - BACKGROUND/AIMS: Hepatic injury induced by ischemia/reperfusion following
      surgery, transplantation, or circulatory shock combined with resuscitation is a
      major clinical problem. METHODS: In this study, hypoxic and inflammatory
      conditions were mimicked by exposing human hepatocytes to N(2) (at 4 and 37
      degrees C) or to cytokines/endotoxin to investigate the potential protective
      effects of heme oxygenase-1 (HO-1). Incubation of human hepatocytes with single
      cytokines (IFN-gamma, IL-1beta, TNF-alpha) or LPS, as well as a combination of
      all four stimuli (CM, cytomix) caused a time-dependent HO-1 mRNA expression over
      12h and a decline by 24 h. In parallel, we observed a time-dependent membrane
      leakage for LDH and AST and a maximum HO-1 protein expression between 3-24 h.
      RESULTS: Warm and cold hypoxia showed similar results in HO-1 mRNA and protein
      expression and the release of LDH and AST. CoPP, a potent HO-1 inducer, and
      bilirubin, a co-product of the HO-pathway, protected human hepatocytes from warm
      and cold hypoxia. HO-1 enzyme activity was highest during warm hypoxia, followed
      by cold hypoxia and CM which was confirmed by intracellular Fe(2+) formation.
      CONCLUSIONS: Taken together, we demonstrated, that HO-1 induction protected human
      hepatocytes against warm and cold hypoxia. Our results also suggest that HO-1
      induction may have therapeutic potential against inflammatory insults.

PMID- 15519650
TI  - Inhibition of inducible nitric oxide synthase protects against liver injury
      induced by mycobacterial infection and endotoxins.
AB  - BACKGROUND/AIMS: Bacillus Calmette Guerin (BCG) infection causes hepatic injury
      following granuloma formation and secretion of cytokines which render mice highly
      sensitive to endotoxin-mediated hepatotoxicity. This work investigates the role
      of inducible nitric oxide synthase (iNOS) in liver damage induced by BCG and
      endotoxins in BCG-infected mice. METHODS: Liver injury and cytokine activation
      induced by BCG and by LPS upon BCG infection (BCG/LPS) were compared in wild-type
      and iNOS-/- mice. RESULTS: iNOS-/- mice infected with living BCG are protected
      from hepatic injury when compared to wild-type mice which express iNOS protein in
      macrophages forming hepatic granulomas. In addition, iNOS-/- mice show a decrease
      in BCG-induced IFN-gamma serum levels. LPS challenge in BCG-infected mice
      strongly activates iNOS in the liver and spleen of wild-type mice which show
      important liver damage associated with a dramatic increase in TNF and IL-6 and
      also Th1 type cytokines. In contrast, iNOS-/- mice are protected from liver
      injury after BCG/LPS challenge and their TNF, IL-6 and Th1 type cytokine serum
      levels raise moderately. CONCLUSIONS: These results demonstrate that nitric oxide
      (NO) from iNOS is involved in hepatotoxicity induced by both mycobacterial
      infection and endotoxin effects upon BCG infection and that inhibition of NO from
      iNOS protects from liver injuries.

PMID- 15519651
TI  - Interferon-alphaCon1 suppresses proliferation of liver cancer cell lines in vitro
      and in vivo.
AB  - BACKGROUND/AIMS: We investigated the effects of consensus interferon (IFN
      alphaCon1), a nonnaturally occurring type I interferon with higher specific
      activity than other type I IFNs, on the growth of human liver cancer cells.
      METHODS: The effect of IFN-alphaCon1 on the proliferation of 13 liver cancer cell
      lines was investigated in vitro. Hepatocellular carcinoma (HCC) cells (KIM-1 and
      HAK-1B) were transplanted subcutaneously into the back of nude mice, then IFN
      alphaCon1 was subcutaneously administered to the mice once a day for 2 weeks, and
      tumor volume and histology were examined. RESULTS: IFN-alphaCon1 expressed a dose
      dependent growth inhibitory effect in all cell lines in vitro. KIM-1 tumor volume
      in mice that received 0.01 microg (10(4)IU)/mouse/day of IFN-alphaCon1 (similar
      to the clinical dose for chronic hepatitis C) was 62% of the control,
      0.1microg/mouse/day resulted in 26%, and 1 microg/mouse/day resulted in 10%. HAK
      1B tumor volume under the same treatment was 61, 24 and 0% of the control,
      respectively. The number of apoptotic cells significantly increased and the
      number of blood vessels significantly decreased with the increase in IFN
      alphaCon1 dose. CONCLUSIONS: IFN-alphaCon1 suppressed HCC growth in nude mice.
      These data indicate the potential clinical application of IFN-alphaCon1 in the
      prevention and treatment of HCC.

PMID- 15519652
TI  - Suppression of C/EBP alpha expression in biliary cell differentiation from
      hepatoblasts during mouse liver development.
AB  - BACKGROUND/AIMS: Intrahepatic biliary cell differentiation takes place in
      periportal hepatoblasts under the influence of the subjacent mesenchyme, which
      leads to the suppression of mature hepatocyte marker expression. This study was
      undertaken to analyze C/EBP alpha and beta expression, which may govern
      transcription of mature hepatocyte marker genes, during mouse liver development
      with special attention given to biliary differentiation. METHODS: Expression of
      C/EBP alpha and beta was immunohistochemically examined. Expression of alpha
      fetoprotein, albumin and urea cycle enzymes, the genes of which have CCAAT motifs
      in their upstream regulatory sequences, was examined immunohistochemically or by
      using in situ hybridization. RESULTS: C/EBP alpha started to be expressed in
      endodermal cells of 9.5-day liver primordium, and continued to be expressed in
      hepatoblasts and hepatocytes throughout development. Although biliary cell
      progenitors transiently expressed mature hepatocyte markers, their expression of
      C/EBP alpha was weak or totally absent. The signals of C/EBP beta in hepatocytes
      were weak in fetal liver, but became stronger with postnatal development.
      Differentiated epithelial cells of intrahepatic biliary structures did not
      express C/EBP alpha. CONCLUSIONS: These data suggest that the suppression of
      C/EBP alpha expression may be prerequisite to biliary cell differentiation in the
      hepatoblast population and one of its earliest signs.

PMID- 15519653
TI  - Peripheral benzodiazepine receptor ligands induce apoptosis and cell cycle arrest
      in human hepatocellular carcinoma cells and enhance chemosensitivity to
      paclitaxel, docetaxel, doxorubicin and the Bcl-2 inhibitor HA14-1.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is one of the most common causes
      of cancer deaths worldwide. Thus, novel therapies are urgently needed. A
      promising approach is the use of peripheral benzodiazepine receptor (PBR) ligands
      which inhibit the proliferation of various tumors. METHODS: PBR expression both
      in human HCC cell lines and in tumor specimens of HCC patients was analyzed by RT
      PCR and immunostaining. To evaluate PBR ligands for the treatment of HCC, we
      tested their effects on human HCC cells. RESULTS: PBR was localized to the
      mitochondria both of HCC cell lines and tumor tissues of HCC patients. In
      contrast, normal liver did not express PBR. PBR ligands inhibited the
      proliferation of HCC cell lines by inducing apoptosis and cell cycle arrest.
      Apoptosis was characterized by a breakdown of the mitochondrial membrane
      potential, caspase-3 activation and nuclear degradation. Furthermore, pro
      apoptotic Bax was overexpressed while anti-apoptotic Bcl-2 and Bcl-X(L) were
      suppressed. Cell cycle was arrested both at the G1/S- and G2/M-checkpoints.
      Synergistic anti-neoplastic effects were obtained by a combination of PBR ligands
      with cytostatic drugs (paclitaxel, docetaxel, doxorubicin), or with an
      experimental Bcl-2 inhibitor. CONCLUSIONS: This is the first report on the
      induction of apoptosis and cell cycle arrest by PBR ligands in HCC cells.
      Moreover, PBR ligands sensitized HCC cells to taxans and doxorubicin.

PMID- 15519654
TI  - Enhanced epidermal growth factor receptor activation in human cholangiocarcinoma
      cells.
AB  - BACKGROUND/AIMS: Epidermal growth factor receptor (EGFR) signaling has been
      implicated in the genesis and progression of cholangiocarcinoma. However, the
      characteristics of EGFR signaling in cholangiocarcinoma cells have not been
      characterized. Thus, we attempted to more fully characterize EGF/EGFR signaling
      in human cholangiocarcinoma cells. METHODS: EGFR phosphorylation and
      ubiquitination were evaluated using immunoblot techniques. EGFR internalization
      was analyzed by immunofluorescent staining of EGFR or by immunoblot analysis for
      biotinylated EGFR. Cell growth was assessed using the MTS assay. RESULTS: EGFR
      activation was sustained following EGF stimulation in cholangiocarcinoma cells as
      compared to hepatoma cells. This prolonged EGFR activation resulted in extended
      p42/44 MAPK activation in cholangiocarcinoma cells. Despite ubiquitination, EGFR
      activation-dependent internalization was defective in cholangiocarcinoma cells.
      Cell growth was increased in cholangiocarcinoma cells following EGF stimulation
      as compared to hepatoma cells, and this was significantly attenuated by EGFR
      kinase inhibitors. The EGFR kinase inhibitors also significantly decreased COX-2
      expression in cholangiocarcinoma cells, while this was not evident in hepatoma
      cells. CONCLUSIONS: The results demonstrate that cholangiocarcinoma cells exhibit
      sustained EGFR activation due to defective receptor internalization. As EGFR
      kinase inhibitors effectively attenuated cellular growth, these agents may be
      therapeutically efficacious in human cholangiocarcinoma.

PMID- 15519655
TI  - Vitamin E down-modulates iNOS and NADPH oxidase in c-Myc/TGF-alpha transgenic
      mouse model of liver cancer.
AB  - BACKGROUND/AIMS: Co-expression of c-Myc and TGF-alpha in the mouse liver
      accelerates hepatocarcinogenesis and enhances DNA damage due to chronic oxidative
      stress. Dietary supplementation with vitamin E (VE) inhibits hepatocarcinogenesis
      and reduces chromosomal alterations in the same mice. Here we investigated the
      sources of reactive oxygen species (ROS) production in c-Myc/TGF-alpha transgenic
      mice. METHODS: Inducible nitric oxide synthase (iNOS) and NADPH oxidase levels
      were determined in c-Myc, TGF-alpha and c-Myc/TGF-alpha mice by RT-PCR, western
      blot analysis and immunohistochemistry. RESULTS: iNOS and nitrotyrosines levels
      were higher in the three transgenic lines when compared with wild-type mice.
      Preneoplastic and neoplastic lesions from c-Myc, TGF-alpha and c-Myc/TGF-alpha
      transgenic mice displayed upregulation of NADPH oxidase subunits p47-, 67-phox,
      Rac1, HSP 70, and HO-1. Importantly, dietary supplementation with vitamin E
      abolished iNOS expression, lowered nitrotyrosines, p47-, p67-phox, and Rac1
      levels, and suppressed HSP 70 and HO-1 proteins in c-Myc/TGF-alpha livers.
      CONCLUSIONS: The results suggest that iNOS and NADPH oxidase are involved in ROS
      generation during c-Myc/TGF-alpha hepatocarcinogenesis and are inhibited by VE
      treatment. The data provide additional evidence for the potential use of VE in
      treatment of chronic liver diseases and HCC prevention.

PMID- 15519656
TI  - Involvement of c-Myc in growth inhibition of Hep 3B human hepatoma cells by a
      vitamin K analog.
AB  - BACKGROUND/AIMS: A synthetic vitamin K analog, compound 5 (Cpd 5), is a potent
      inhibitor of cell growth. The aim was to investigate whether c-Myc was involved
      in Cpd 5-induced cell growth inhibition. METHODS: Human hepotoma cells (Hep 3B)
      were cultured and treated with Cpd 5, and c-Myc protein expression and
      phosphorylation were investigated using Western blot analysis. RESULTS: Cpd 5 was
      found to inhibit c-Myc protein expression and induce c-Myc phosphorylation in Hep
      3B cells. The phosphorylation of c-Myc was induced by both Cpd 5-mediated
      persistent extracellular signal-regulated kinase (ERK) phosphorylation and Cpd 5
      increased glycogen synthase kinase-3 (GSK-3) activity. When using GSK-3
      inhibitor, SB216763, c-Myc phosphorylation was significantly decreased and c-Myc
      levels were restored in Cpd 5 treated cells, suggesting that Cpd 5-mediated
      increase of GSK-3 activity enhanced c-Myc degradation and resulted in reduction
      of c-Myc levels. The lower c-Myc levels were found to cause altered expression of
      two c-Myc target genes, growth arrest gene gadd45 and ornithine decarboxylase
      (ODC). CONCLUSIONS: The results suggest that Cpd 5-mediated c-Myc phosphorylation
      resulted in enhanced c-Myc protein degradation and reduced c-Myc protein levels,
      which may contribute to cell growth inhibition by Cpd 5.

PMID- 15519657
TI  - Fibrosis progression after liver transplantation in patients with recurrent
      hepatitis C.
AB  - BACKGROUND/AIMS: Aim of our study was to analyze fibrosis progression after liver
      transplantation (OLT) in hepatitis C virus (HCV)-infected patients based on
      protocol liver biopsies and to identify risk factors, which may play a role in
      the development of severe fibrosis stages. METHODS: One hundred and eighty-three
      liver graft recipients who had a histological follow-up evaluation of 1 year
      after OLT were analyzed. Overall 1039 protocol liver biopsies were performed
      after 1-, 3-, 5-, 7- and 10 years and staged according to the Scheuer score.
      RESULTS: The fibrosis progression rate was not linear. The fibrosis scores were
      1.2 after one, 1.7 after three, 1.9 after five, 2.1 after 7 and 2.2 after 10
      years. The 39 recipients with fibrosis stages 3 or 4 in the 1-year biopsy had a
      significantly reduced survival rate, while fibrosis stage 0-2 indicated excellent
      survival. Independent risk factors for progression of fibrosis at 1 year were HCV
      genotype 1 and 4 (P=0.01) and donor age>33 years (P=0.01), whereas risk factors
      for development of cirrhosis (30/183 recipients (16%)) were donor age (P=0.002)
      and multiple steroid pulses (P=0.05). CONCLUSIONS: These data provide information
      on the course of recurrent hepatitis C and may be helpful to individualize the
      treatment of transplanted patients.

PMID- 15519658
TI  - Regional and transient ischemia/reperfusion injury in the liver improves
      therapeutic efficacy of allogeneic intraportal hepatocyte transplantation in low
      density lipoprotein receptor deficient Watanabe rabbits.
AB  - BACKGROUND/AIMS: Hepatocyte transplantation has the potential to become an
      alternative to organ transplantation for the treatment of hereditary liver
      disease. Currently used hepatocyte transplantation techniques are often not
      sufficient for phenotypic correction. In a pre-clinical model we investigated the
      effect of regional transient ischemia reperfusion injury and repeated infusions
      of allogeneic hepatocytes on LDL cholesterol levels in LDL receptor deficient
      hyperlipidemic Watanabe rabbits. METHODS: A catheter was surgically inserted into
      the inferior mesenteric vein. Blood supply to the right liver lobe was
      transiently interrupted. Nine infusions of 2.5x10(7) adult allogeneic hepatocytes
      from white New Zealand rabbits were applied over a period of 2 months. RESULTS:
      Compared to pretreatment levels LDL cholesterol decreased significantly in
      Watanabe rabbits with transient ischemia reperfusion injury and repeated
      hepatocyte transplantation (-42+/-3%). Repeated hepatocyte transplantation
      without transient ischemia reperfusion injury decreased LDL cholesterol levels
      only moderately (-11+/-4%). LDL receptor messenger RNA and proteins were detected
      in hepatocyte transplanted liver but not in the liver of sham treated animals.
      CONCLUSIONS: Our data indicate that transient ischemia reperfusion injury of the
      recipient liver is safe and significantly improves the therapeutic efficacy of
      allogeneic hepatocyte transplantation in hyperlipidemic rabbits with congenital
      LDL receptor deficiency.

PMID- 15519659
TI  - Hepatitis C virus infection affects the brain-evidence from psychometric studies
      and magnetic resonance spectroscopy.
AB  - BACKGROUND/AIMS: Up to 50% of patients infected with the hepatitis C virus (HCV)
      complain of chronic fatigue and difficulties in concentration and memory. The aim
      of the present study was to seek evidence for the presence of central nervous
      system involvement in HCV infected patients with only mild liver disease.
      METHODS: Thirty HCV infected patients with normal liver function, 15 of whom were
      identified as having mild and 15 moderate to severe fatigue using the fatigue
      impact scale, underwent neurological and neuropsychological examination,
      electroencephalography (EEG) and cerebral proton magnetic resonance imaging (MRI)
      and spectroscopy (MRS). Fifteen healthy volunteers, matched for age and
      educational attainment, served as controls. RESULTS: In comparison to the healthy
      controls the patients with HCV infection showed evidence of cognitive impairment,
      primarily attention and higher executive functions, higher levels of anxiety and
      depression and impairment of quality of life. In addition they showed a
      significant decrease of the N-acetyl-aspartate/creatine ratio in the cerebral
      cortex on 1H MRS while the EEG was slowed in 25%. In general the deficits were
      more marked in the patients with moderate rather than mild fatigue. CONCLUSIONS:
      The data provide evidence of central nervous system involvement in patients with
      HCV infection.

PMID- 15519660
TI  - Safety and efficacy of alamifovir in patients with chronic hepatitis B virus
      infection.
AB  - BACKGROUND/AIMS: Alamifovir is a purine nucleotide analogue prodrug that shows
      potent activity against wild type and lamivudine resistant hepatitis B virus in
      preclinical studies. The aim of this study was to assess the safety and potential
      antiviral effects of alamifovir in humans. METHODS: A randomised, placebo
      controlled, dose escalation study of oral alamifovir was conducted in 66 chronic
      hepatitis B infected patients who were selected based on stable HBV DNA
      (>10(5)copies/ml), with no significant liver pathology. They received either
      placebo or alamifovir at a total daily dose ranging from 2.5 to 20mg in single or
      divided doses for 28 days and were followed up for approximately 12 weeks after
      cessation of treatment. RESULTS: All doses showed significant antiviral activity,
      with mean plasma viral load reductions ranging from 1.5 to 2.6 log(10) after 28
      days of dosing. Once and twice daily regimen for the same daily dose (5mg BID vs
      10mg QD, 10mg BID vs 20mg QD) showed no apparent difference in the rate and
      extent of viral decline, or viral reduction at day 28. Post-treatment viral
      suppression was dose dependent. There were no serious adverse events attributable
      to study drug, nor were significant dose related events identified. CONCLUSIONS:
      Alamifovir has shown potent in vivo anti-HBV activity, with a favourable safety
      profile.

PMID- 15519661
TI  - Sustained activation of epidermal growth factor receptor in cholangiocarcinoma: a
      potent therapeutic target?

PMID- 15519662
TI  - Fibrosis progression after liver transplantation in patients with recurrent
      hepatitis C.

PMID- 15519663
TI  - Angiogenesis and hepatocellular carcinoma.

PMID- 15519664
TI  - Membranoproliferative glomerulonephritis associated with hepatitis C infection.

PMID- 15519665
TI  - Spontaneous recovery in neonatal hemochromatosis.

PMID- 15519666
TI  - Up and down regulation of apoptosis in hepatitis C virus-related liver damage.

PMID- 15519668
TI  - Sampling variability in liver biopsies.

PMID- 15519670
TI  - Distribution of metabotropic P2Y receptors in the rat retina: a single-cell RT
      PCR study.
AB  - P2Y receptors are metabotropic G-protein linked purinergic receptors, which are
      especially widespread in the central nervous system. The purpose of the present
      study was to determine the distribution patterns of P2Y receptors in distinct
      retinal cell types in the adult retina. Retinal ganglion cells (RGC), bipolar
      cells (BPC) and Muller cells (MC) of adult pigmented rats were analyzed for their
      expression of P2Y-receptor subtypes P2Y1, P2Y2, P2Y4, and P2Y6 by single-cell
      reverse transcription polymerase chain reaction (SC-RT-PCR). SC-RT-PCR resulted
      in a positive amplification signal for all P2Y-receptor subtype mRNAs in all cell
      types examined. However, subtype distribution differed among the different cell
      types. The percentage of cells expressing a distinct P2Y subtype was: (a) for
      RGCs: 80% with P2Y1, 100% with P2Y2, 30% with P2Y4 and 50% with P2Y6, (b) for
      BPCs: 60% with P2Y1, 40% with P2Y2, 20% with P2Y4 and 80% with P2Y6, and (c) for
      MCs: 60% with P2Y1, 80% with P2Y2, 60% with P2Y4 and 100% with P2Y6. Our data
      show that different subtypes of P2Y receptors (P2Y1, P2Y2, P2Y4 and P2Y6) are
      expressed in various retinal cells and indicate that extracellular purines and
      pyrimidines act on RGCs, BPCs and MCs via different P2Y receptors.

PMID- 15519671
TI  - Effect of transgene copy number on survival in the G93A SOD1 transgenic mouse
      model of ALS.
AB  - Transgenic mice expressing multiple copies of the G93A mutant form of SOD1
      develop motor neuron pathology and clinical symptoms similar to those seen in
      patients with amyotrophic lateral sclerosis (ALS). The phenotype of these mice is
      dependent on the number of transgene copies in their genome. Changes in transgene
      copy number, although rare, can sometimes occur while mating due to intra locus
      recombination events during meiosis. The objective of this study was to develop a
      real time quantitative PCR method to determine changes in transgene copy number
      in these mice and to evaluate the effect of transgene copy number on the
      phenotype of the G93A SOD1 mouse model of ALS.

PMID- 15519672
TI  - Mice with a fra-1 knock-in into the c-fos locus show impaired spatial but regular
      contextual learning and normal LTP.
AB  - The immediate early gene c-fos is part of the AP-1 transcription factor complex,
      which is involved in molecular mechanisms underlying learning and memory. Mice
      that lack c-Fos in the brain show impairments in spatial reference and contextual
      learning, and also exhibit a reduced long-term potentiation of synaptic
      transmission (LTP) at CA3-to-CA1 synapses. In the present study, we investigated
      mice in which c-fos was deleted and replaced by fra-1 (c-fos(fra-1) mice) to
      determine whether other members of the c-fos gene family can substitute for the
      functions of the c-fos gene. In c-fos(fra-1) mice, both CA3-to-CA1 LTP and
      contextual learning in a Pavlovian fear conditioning task were similar to wild
      type littermates, indicating that Fra-1 expression restored the impairments
      caused by brain-specific c-Fos depletion. However, c-Fos-mediated learning
      deficits in a reference memory task of the Morris watermaze were also present in
      c-fos(fra-1) mice. These findings suggest that different c-Fos target genes are
      involved in LTP, contextual learning, and spatial reference memory formation.

PMID- 15519673
TI  - Bacterial endotoxin induces IL-20 expression in the glial cells.
AB  - The regulatory mechanisms leading to IL-20 expression during infection have not
      been elucidated. In the present study, we found that bacterial lipopolysaccharide
      (LPS) induced IL-20 expression in the primary cultured glial cells and RAW264.7
      macrophage cell line. Pretreatment with protein synthesis inhibitor puromycin or
      cycloheximide failed to inhibit the expression of IL-20, suggesting that the
      expression was not dependent on de novo protein synthesis. Myeloid
      differentiation factor 88 (MyD88) is an important adaptor molecule for Toll-like
      receptor signaling. We observed complete inhibition of LPS-induced expression of
      IL-20 in the primary cultured glial cells prepared from MyD88-deficient mice.
      Furthermore, a p38 MAP kinase inhibitor, SB203580, inhibited LPS-induced
      expression of IL-20 mRNA. LPS-induced p38 MAP kinase phosphorylation was delayed
      in MyD88-deficient glial cells. Therefore, it is suggested that LPS induces IL-20
      expression through MyD88-p38-dependent mechanisms. As dexamethasone inhibited LPS
      induced IL-20 expression, the expression of IL-20 is regulated by a negative
      feedback loop mediated through glucocorticoids. Therefore, it is suggested that
      IL-20 may play a crucial role in inflammatory conditions in the brain.

PMID- 15519674
TI  - Induction of murine HRD1 in experimental cerebral ischemia.
AB  - Hrd1p in yeast plays an important role in endoplasmic reticulum-associated
      degradation (ERAD). In the present study, we used an in vivo model of hypoxia
      ischemia in mice to study the expression of murine HRD1. Hypoxia-ischemia induced
      a significant increase in mRNA levels of genes including GRP78, CHOP and MyD116,
      the expression of which are specifically activated under conditions associated
      with ER dysfunction. The level of mHRD1 mRNA was significantly increased after
      ischemia. Interestingly, induction of mHRD1 was elevated at a later time point
      (12-48 h) in the ischemic cortex, whereas it increased at an earlier time point
      (3-12 h) in the injured striatum. We also examined the changes of mHRD1 mRNA
      expression in neuroblastoma Neuro2a and primary glial cells exposed to
      hypoxia/reoxygenation. The expression of mHRD1 mRNA was remarkably up-regulated
      in glial cells subjected to 24 h hypoxia, whereas no significant changes were
      observed in Neuro2a cells under hypoxia/reoxygenation. In addition, the levels of
      mHRD1 mRNA were markedly elevated in glial cells exposed to treatment with
      tunicamycin (Tm, an ER stress inducer). These findings suggest that hypoxia
      ischemia triggers ER dysfunction and mHRD1 may play a role in ischemia-induced ER
      dysfunction.

PMID- 15519675
TI  - Age-dependent effects of serotonin-1A receptor gene deletion in spatial learning
      abilities in mice.
AB  - The serotonin (5-hydroxytryptamine, 5-HT) receptor 1A is involved in many
      physiological functions, including the regulation of learning and memory by
      acting either as an autoreceptor located on 5-HT neurons (raphe nuclei) or as a
      heteroreceptor on non-5-HT neurons, mainly in the hippocampal formation. To
      investigate whether the effects of 5-HT via 5-HT1A receptors on learning are age
      sensitive, we evaluated the performance of young-adult (3 months old) and aged
      (22 months old) 5-HT1A knockout (KO) mice and their homologous wild types (WT) in
      the hippocampal-dependent spatial reference memory version of the Morris water
      maze. We demonstrated that young-adult 5-HT1AKO mice exhibit an impairment in
      learning and retention of the spatial task, as compared to WT mice, without
      showing any sign of change in their sensori-motor and locomotor abilities or
      motivation. This genotype effect does not persist during aging. In fact, aged 5
      HT1AKO mice seem to be slightly facilitated during the early stages of learning.
      These results are consistent with a possible prevalence of 5-HT1A raphe functions
      in learning and memory abilities of young-adult animals, since the effects of the
      mutation on mice performance (impairment) are opposite to those found after intra
      raphe injection of 5-HT1A agonists (facilitation), and with data showing
      increased activity of 5-HT neurons in 5-HT1AKO mice. The reduced effect of the
      mutation in aged animals possibly reflects the lower efficacy of autoreceptors
      due to aging and/or a prevalence of hippocampal heteroreceptors.

PMID- 15519676
TI  - A real-time quantitative PCR comparative study between rat optic and sciatic
      nerves: determination of neuregulin-1 mRNA levels.
AB  - Injured axons from peripheral nervous system (PNS) possess the ability to
      regenerate. In contrast, regeneration of injured axons does not occur in the
      central nervous system (CNS) or occurs to a limited extent. Previous works have
      shown that rat sciatic nerve conditioned medium (CM) produced PC12 cells neuronal
      like differentiation and neurite outgrowth. In the present work, we compared the
      expression of neuregulin-1s (NRG-1s) from rat sciatic and optic nerves as members
      of the PNS and CNS, respectively. Sciatic nerve CM showed a higher neurotrophic
      activity on PC12 cells than rat optic nerve CM. RT-PCR analysis verified the
      presence of all three types of NRG-1 mRNAs and their receptors in both types of
      nerves. Real-time quantitative PCR (QPCR) assays showed that the relative
      expression levels of all three types of NRG-1 mRNAs were higher in optic nerves
      than in sciatic nerves. Eleven-day cultured optic nerves showed an increased in
      NDF and SMDF when compared to freshly isolated optic nerves, whereas GGF
      decreased. However, 11-day-cultured sciatic nerves only showed an increase in
      SMDF mRNA. Western blots corroborated the differences in NRG-1 expression profile
      for both types of nerves and their CMs. Incubation of both CMs with the anti-pan
      NRG-1 antibody showed that the neurotrophic activity of the optic nerve CM
      increased, whereas the sciatic nerve CM remained unchanged. These results
      indicated that different NRG-1 levels are expressed upon nerve degeneration and
      the balance between those levels and other neurotrophic factors could have an
      important role on nerve regeneration.

PMID- 15519677
TI  - Effects of selective D1- or D2-like dopamine receptor antagonists with acute
      "binge" pattern cocaine on corticotropin-releasing hormone and
      proopiomelanocortin mRNA levels in the hypothalamus.
AB  - We have previously demonstrated that there are stimulatory effects of acute (1
      day) "binge" cocaine on corticotropin-releasing hormone (CRH) gene expression in
      the rat hypothalamus and on the stress responsive hypothalamic-pituitary-adrenal
      (HPA) activity. The first aim of the present study was to investigate the
      possible role of dopamine (DA) D1- or D2-like receptors (D1R or D2R) in
      modulating these acute effects. Administration of acute "binge" cocaine (3x15
      mg/kg, i.p.) was preceded by injections of either the selective D1R antagonist
      (SCH23390, 2 mg/kg) or D2R antagonist (sulpiride, 50 mg/kg). The D1R or D2R
      blockade by SCH23390 or sulpiride, respectively, did not alter the mRNA levels of
      CRH in the hypothalamus, CRH-R1 or proopiomelanocortin (POMC) in the anterior
      pituitary. However, the acute "binge" cocaine-induced increase in hypothalamic
      CRH mRNA levels was not found in the rats that received either D1R or D2R
      antagonist pretreatment. In the anterior pituitary, acute "binge" cocaine or its
      combinations with either DA antagonist did not alter CRH-R1 receptor or POMC mRNA
      levels. Both the D1R and D2R antagonists attenuated the elevation of plasma
      corticosterone levels induced by acute "binge" cocaine. These results suggest
      that both D1R and D2R mediate acute cocaine's stimulatory effect on HPA axis at
      the hypothalamic CRH level. Neurobiological evidence has demonstrated functional
      interactions between dopaminergic and opioidergic systems that regulate
      preproenkephalin and preprodynorphin gene expression in the striatum. The second
      aim of our study was to investigate the roles that D1R or D2R could play in
      regulation of POMC mRNA levels in the hypothalamus in response to acute "binge"
      cocaine. The D2R blockade by sulpiride increased POMC mRNA levels in the
      hypothalamus, indicating that D2R exerts a tonic inhibitory effect on
      hypothalamic POMC gene expression. The POMC mRNA increases induced by the D2R
      blockade were attenuated by acute "binge" cocaine. Neither the D2R blockade nor
      acute "binge" cocaine altered POMC mRNA levels in the amygdala, anterior
      pituitary or neurointermediate lobe of the pituitary. In contrast to the D2R, the
      D1R blockade by SCH23390, acute "binge" cocaine or their combination had no
      effect on hypothalamic POMC mRNA levels. These results support a specific role
      for D2R in acute cocaine's effects on hypothalamic POMC gene expression.

PMID- 15519678
TI  - Identification of a novel alternative splicing form of human netrin-4 and
      analyzing the expression patterns in adult rat brain.
AB  - Netrins are a family of secreted proteins that function as tropic cues directing
      axon growth and cell migration during neural development. Beta-netrin or netrin-4
      (NTN4), the fourth member of this family, was previously reported by Koch (M.
      Koch, J.R. Murrell, D.D. Hunter, P.F. Olson, W. Jin, D.R. Keene, W.J. Brunken,
      R.E. Burgeson. A novel member of the netrin family, beta-netrin, shares homology
      with the beta chain of laminin: identification, expression, and functional
      characterization. J. Cell Biol. 151 (2000) 221-234) and Yin (Y. Yin, J.R. Sanes,
      J.H. Miner, Identification and expression of mouse netrin-4. Mech. Dev. 96 (2000)
      115-119), respectively. However, whether there is another isoform of netrin-4 and
      the expression patterns have not been fully determined. Here we report the
      cloning of a novel isoform of human netrin-4 using rapid amplification of
      complementary DNA (cDNA) ends (RACE) technique and analysis on the netrin-4 mRNA
      expression in adult rat brain using in situ hybridization. The new isoform lacks
      the signal peptide region and might represent a truncated form at the Laminin-N
      terminal domain of human netrin-4. Examination of the expression pattern of
      netrin-4 mRNA in adult rat brain revealed that the netrin-4 mRNA was widely
      expressed in many regions of the brain. High levels of netrin-4 mRNA was found in
      the pyramidal cell layer of the cerebral cortex, prepiriform cortex, amygdaloid
      nuclei, pyramidal layer of hippocampus, Purkinje's cells, medial cerebellar
      nucleus and interposed cerebellar nucleus, medial nucleus of the trapezoid body
      and mitral cell layer of the olfactory bulb. Moderate signals were present in
      frontal cortex, several thalamic and hypothalamic nuclei. The widespread
      expression of netrin-4 in adult rat brain indicates that netrin-4 is not only
      important for axon guidance during embryonic development, but also critical to
      neuronal plasticity in adult stage.

PMID- 15519679
TI  - Overexpression of the full-length neurotrophin receptor trkB regulates the
      expression of plasticity-related genes in mouse brain.
AB  - Significant body of evidence indicates an important role for brain-derived
      neurotrophic factor (BDNF) in the hippocampal synaptic plasticity; however, the
      exact mechanisms how the BDNF signal is converted to plastic changes during
      memory processes are under an intense investigation. To specifically address the
      role of the trkB receptor, we have previously generated transgenic mice
      overexpressing the full-length trkB receptor and observed a continuous activation
      of the trkB.TK+ receptor, improved learning and memory but an attenuated LTP in
      these mice. In this study, we describe the trkB.TK+ mRNA and protein distribution
      in the transgenic mice, showing the most prominent increase in the full-length
      trkB expression in the cortical layer V pyramidal neurons and dentate gyrus of
      the hippocampus. In addition, we have analyzed the mRNA expression patterns of a
      group of genes associated with both plastic changes in the nervous system and
      BDNF signaling. Regulated expression of immediate early genes c-fos, fra-2 and
      junB was observed in the transgenic mice. Furthermore, the mRNA expression of
      alpha-Ca2+/calmodulin-dependent kinase II (alpha-CaMKII) was reduced in both the
      hippocampus and parietal cortex, whereas growth-associated protein 43 (GAP-43)
      mRNA expressions were induced in the corresponding regions. Conversely, the mRNA
      expression of the transcription factor cAMP response element binding protein
      (CREB) was not altered in the trkB.TK+mice. Finally, the density of neuropeptide
      Y (NPY)-expressing cells was increased in the trkB.TK+ mice dentate hilus.
      Altogether, these results demonstrate in vivo that the increased trkB.TK+
      signaling regulates several important plasticity-related genes.

PMID- 15519680
TI  - Heat acclimation affects the neuromodulatory role of AngII and nitric oxide
      during combined heat and hypohydration stress.
AB  - We studied the effect of heat acclimation on the neuromodulatory role of
      angiotensin (AngII) and nitric oxide during combined heat (39 degrees C) and
      hypohydration (water deprivation, -10% body weight) stress. Rats were divided
      into control (C), short (2d-STHA) or long (30d-LTHA) acclimation (34 degrees C)
      groups. AngII, 7-nitroindazole (7NI)-nNOS blocker, or both were centrally
      administered (5 mul, bolus) under light chloroform anesthesia prior to each
      experimental paradigms: (1) In vivo: measurements of skin-vasodilatation (VTsh)
      and salivation-cooling (STsh) thresholds, and heat endurance in conscious
      heat/hypohydrated stressed rats; (2) expression of AT(1) and AT(2) AngII
      receptors and nNOS were measured in the hypothalamus (Western blot); (3)
      transcript levels of the coding genes were measured using real-time PCR. A
      synthesis of the results shows a biphasic acclimatory profile of VTsh, STsh, and
      transcript levels of all studied genes, with transient up/down-regulatory changes
      on STHA. AngII affected the physiological integrative outcome primarily during
      euhydration, although AT membranal changes (except in LTHA) were confined to
      hypohydration. 7NI had an impact during hypohydration. Evidence is provided that
      AngII and 7NI modulate thermoregulation primarily via AT(1) and AT(2) receptors,
      with predominance of AT(2) signaling following LTHA and/or hypohydration,
      opposing a drop in AT(1)-mediated thresholds. The final shaping of AngII
      signaling depends on cross-talk between nNOS and AngII receptors at both
      molecular and protein levels. Hypohydration induces transcriptional responses but
      desensitizes AngII receptors signaling, attenuating their effect on VTsh and
      STsh, and abolishing the beneficial thermoregulatory effects achieved by heat
      acclimation. nNOS, AngII receptor-independent pathway is also implicated.

PMID- 15519681
TI  - Effect of dark exposure in the middle of the day on Period1, Period2, and
      arylalkylamine N-acetyltransferase mRNA levels in the rat suprachiasmatic nucleus
      and pineal gland.
AB  - The suprachiasmatic nucleus (SCN) of the mammalian hypothalamus contains a
      central circadian pacemaker, which adjusts circadian rhythms within the body to
      environmental light-dark cycles. It has been shown that dark exposure in the day
      causes phase shifts in circadian rhythms, but it does not induce changes in the
      melatonin levels in the pineal gland. In this study, we examined the effect of
      dark exposure on two "circadian clock" genes Period1 and Period2 mRNA levels in
      the rat SCN, and on Period1, Period2, and arylalkylamine N-acetyltransferase (Aa
      Nat, the rate-limiting enzyme in melatonin synthesis) gene expression in the
      pineal gland. Period1 and Period2 mRNA levels were significantly decreased in the
      SCN after 0.5 and 2 h, respectively, therefore suggesting that changes in those
      mRNA levels may be the part of the mechanisms of dark-induced phase shifts.
      Period1 and Aa-Nat mRNA levels in the pineal gland were not affected by darkness,
      but Period2 was moderately affected. Since Period1 and Aa-Nat mRNA levels in the
      pineal gland did not respond to dark stimulation, we further examined whether the
      pineal gland itself is capable of responding to adrenergic stimulation at this
      time of the day. Isoproterenol significantly induced Period1 and Aa-Nat mRNA
      levels; however, it did not affect Period2. Although previous studies have
      reported that during the day the SCN "gates" the dark information reaching the
      pineal, our data demonstrate that dark information may reach the pineal during
      the daytime.

PMID- 15519682
TI  - Differential regulation of short and long dopamine D2 receptor mRNA levels by
      hypoxia in the adrenals of 1-day-old and adult rabbits.
AB  - We tested the hypothesis that hypoxic exposure exerts distinct modulation on the
      mRNA level of the short and long isoform of the D2 dopamine (DA) receptor (D(2)r)
      and on tyrosine hydroxylase (TH) in the adrenals and superior cervical ganglion
      (SCG) of 1-day-old and adult rabbits. One-day-old and adult rabbits have been
      exposed to moderate (FiO(2): 0.15) or severe (FiO(2): 0.08) hypoxia for 0
      (control), 6 or 24 h. At the end of the hypoxic exposure, the adrenals and SCG
      were rapidly dissected and kept frozen. Standard procedure for Northern blot and
      RT-PCR for evaluation of the short (D(2S)) or long (D(2L)) isoform of D(2)r and
      TH have been used. In the adrenals of adult rabbits, moderate and severe hypoxia
      decreased the D(2S) and D(2L) mRNA with a more prominent effect on the short
      isoform and increased TH mRNA. In 1-day-old rabbits, changes of D(2)r and TH mRNA
      levels were observed only after 24 h of severe or moderate hypoxic exposure and
      only the D(2S) receptor mRNA was significantly reduced. In the SCG, the
      expression level of both TH and D(2)r mRNA were not affected by hypoxic exposure
      in adult and newborn rabbits. Hence, sustained hypoxic exposure exerts distinct
      changes on mRNA level of D(2)r isoform and TH in an age- and tissue-dependent
      pattern.

PMID- 15519683
TI  - Repeated peripheral electrical stimulations suppress both morphine-induced CPP
      and reinstatement of extinguished CPP in rats: accelerated expression of PPE and
      PPD mRNA in NAc implicated.
AB  - Previous studies have shown that peripheral electrical stimulation (PES) can
      suppress morphine-induced conditioned place preference (CPP) and the
      reinstatement of extinguished CPP in the rat. The present study was performed to
      elucidate if preproenkephalin (PPE) and preprodynorphin (PPD) mRNAs in the
      nucleus accumbens (NAc) play a role in this event. Rats were trained with
      morphine for 4 days to establish CPP paradigm. They were then given 15-min test
      once a day for eight consecutive days for extinction trial. Twenty-four hours
      after the 8th session of extinction trials, rats were given peripheral electrical
      stimulation (PES) at 2 or 100 Hz once a day for 3 days, then a morphine-priming
      injection at a dose of 1, 2, or 4 mg/kg to reinstate the extinguished CPP. At the
      end of the experiment, PPE and PPD mRNA levels in the nucleus acccumbens (NAc)
      were determined by the semiquantitative RT-PCR technique. The results showed that
      PES at 2- and 100-Hz administered 30 min a day for 3 days suppressed both the
      expression of morphine-induced CPP and the reinstatement of extinguished CPP. PES
      at 2 Hz increased preproenkephalin (PPE) mRNA levels, whereas PES of 100 Hz that
      of preprodynorphin (PPD) mRNA levels in the NAc. These findings suggest that
      enkephalin and dynorphin in NAc may play important roles in the mechanisms
      underlying the inhibitory effect of PES on the expression and reinstatement of
      morphine-induced CPP in rats.

PMID- 15519684
TI  - Noise overstimulation induces immediate early genes in the rat cochlea.
AB  - In mammals, exposure to intense noise produces a permanent hearing loss called
      permanent threshold shift (PTS), whereas a moderate noise produces only a
      temporary threshold shift (TTS). Little is known about the molecular responses to
      such high intensity noise exposures. In this study we used gene arrays to examine
      the early response to acoustic overstimulation in the rat cochlea. We compared
      cochlear RNA from noise-exposed rats with RNA from unexposed controls. The
      intense PTS noise induced several immediate early genes encoding both
      transcription factors (c-FOS, EGR1, NUR77/TR3) and cytokines (PC3/BTG2, LIF and
      IP10). In contrast, the TTS noise down-regulated the gene for growth hormone. The
      response of these genes to different noise intensities was examined by
      quantitative RT-PCR 2.5 h after the 90-min noise exposure. For most genes, the
      extent of induction correlates with the intensity of the noise exposure. Three
      proteins (EGR1, NUR77/TR3, and IP10) were detected in many regions of the
      unexposed cochlea. After exposure to 120 dB noise, these proteins were present at
      higher levels or showed extended expression in additional regions of the cochlea.
      LIF was undetectable in the cochlea of unexposed rats, but could be seen in the
      organ of Corti and spiral ganglion neurons following noise. NUR77/TR3 was a
      nuclear protein before noise, but following noise translocated to the cytoplasm.
      These studies provide new insights into the molecular response to noise
      overstimulation in the mammalian cochlea.

PMID- 15519685
TI  - Auditory-conditioned-fear-dependent c-Fos expression is altered in the emotion
      related brain structures of Fyn-deficient mice.
AB  - Fyn-tyrosine-kinase-deficient mice exhibit increased fearfulness. To elucidate
      the neural mechanisms of their emotional defects, we compared fyn(-/-) and fyn(+/
      ) mice by behavioral analysis of conditioned fear and by functional
      neuroanatomical analysis of the distribution of highly responsive neurons
      associated with conditioned fear. The mice were exposed to the auditory
      conditioned stimulus paired with electric shock as the unconditioned stimulus.
      After the fear conditioning, auditory stimulus-induced freezing behavior was
      enhanced in fyn(-/-) mice. When the occurrence of c-Fos-immunoreactive neurons in
      the brain of fear-conditioned mice was examined following exposure to the
      auditory stimulus, a significant increase in immunoreactive neurons was found in
      the amygdala, hypothalamus, and midbrain of both genotypes. The occurrence of
      conditioned-fear-dependent c-Fos-immunoreactive neurons was enhanced in the
      central, medial, cortical, and basomedial amygdaloid subdivisions, the
      hypothalamic nuclei, and the midbrain periaqueductal gray of the fyn(-/-) mice in
      comparison with the fyn(+/-) mice. However, remarkably, the occurrence of
      conditioned-fear-dependent c-Fos-immunoreactive neurons was very low in the
      basolateral and lateral amygdaloid subdivisions of the fyn(-/-) mice, in striking
      contrast to a significant increase in c-Fos-immunoreactive neurons in these
      subdivisions in the fyn(+/-) mice. These findings suggest that the increased
      excitability of the specific amygdaloid subdivisions including the central
      nucleus, and of the projection targets such as the hypothalamus and midbrain in
      fyn(-/-) mice, is directly related to the enhanced fear response, and that the
      decreased excitability in the basolateral and lateral amygdaloid subdivisions is
      involved in the defective control of the neural circuit for emotional expression
      in this mutant.

PMID- 15519686
TI  - Altered processing of the amyloid precursor protein and decreased expression of
      ADAM 10 by chronic hypoxia in SH-SY5Y: no role for the stress-activated JNK and
      p38 signalling pathways.
AB  - Clinical studies suggest that the incidence of Alzheimer's disease (AD) is
      increased following an ischaemic or hypoxic episode, such as stroke. Furthermore,
      levels of the AD-associated amyloid beta-peptides (Abeta) and the amyloid
      precursor protein (APP) are enhanced in experimental ischaemia. In our previous
      study [Webster, N.J., Green, K.N., Peers, C., Vaughan, P.F., Altered processing
      of amyloid precursor protein in the human neuroblastoma SH-SY5Y by chronic
      hypoxia, J. Neurochem., 83 (2002) 1262-1271] we reported that exposing cells of
      neuronal origin to a period of chronic hypoxia (CH; 2.5% O(2), 24 h) led to a
      decrease in processing of the amyloid precursor protein (APP) by the alternative
      and neuroprotective alpha-secretase pathway. In SH-SY5Y cells, the most likely
      mechanism was that CH inhibits the protein level of ADAM 10, a disintegrin
      metalloprotease widely believed to be the alpha-secretase. One effect of CH is to
      alter the activity of the stress-activated protein kinases (SAPKs) c-Jun amino
      terminal kinase (JNK) and p38. Thus, the main aims of this study were to
      investigate the effect of CH on (1) the activity of these SAPKs in SH-SY5Y and
      (2) whether changes in the activity of these kinases may account for the CH
      induced decreases in ADAM 10 expression and sAPPalpha secretion. We demonstrated
      that the phosphorylation (activity) of JNK was decreased approximately 50%
      following a period of CH. An inhibitor of JNK did not mimic the effects of CH on
      either ADAM 10 expression or sAPPalpha secretion under conditions in which the
      phosphorylation of c-Jun was inhibited by approximately 80%. Thus the loss of JNK
      activity does not appear to be linked to the decrease in expression of ADAM 10
      and secretion of sAPPalpha. In contrast, phosphorylation (activity) of p38 was
      enhanced approximately 300% following a period of CH. However, inhibitors of p38
      were unable to reverse the loss of sAPPalpha in CH cells, indicating that this
      increase in activity was not linked to the altered processing of APP.

PMID- 15519687
TI  - Differential regulation of multiple brain-derived neurotrophic factor transcripts
      in the postnatal and adult rat hippocampus during development, and in response to
      kainate administration.
AB  - Brain-derived neurotrophic factor (BDNF) is expressed at high levels in the
      hippocampus, where it has been implicated in physiological functions such as the
      modulation of synaptic strength as well as in the pathophysiology of epileptic
      seizures. BDNF expression is highly regulated and the BDNF gene can generate
      multiple transcript isoforms by alternate splicing of four 5' exons (exons I-IV)
      to one 3' exon (exon V). To gain insight into the regulation of different BDNF
      transcripts in specific hippocampal subfields during postnatal development, exon
      specific riboprobes were used. Our data shows that BDNF exon I and exon II mRNAs
      are regulated in hippocampal subfields during postnatal development, in contrast
      to BDNF exon III and exon IV mRNA, which remain relatively stable through this
      period. Further, exons I and II show distinct temporal patterns of expression in
      the hippocampus: BDNF I mRNA peaks in adulthood in contrast to BDNF II mRNA which
      peaks at postnatal day 14 (P14). Finally, we have addressed whether kainate
      treatment in postnatal pups and adults regulates BDNF through the recruitment of
      the same, or distinct, BDNF promoters. Our data indicates that kainate-induced
      seizures induce strikingly different expression of distinct BDNF transcripts,
      both in magnitude as well as spatial patterns in the hippocampal subfields, of
      pups as compared to adults. These results suggest that kainate-mediated seizures
      differentially recruit BDNF promoters in the developing postnatal hippocampus in
      contrast to the adult hippocampus to achieve a hippocampal subfield specific
      regulation of exon-specific BDNF mRNAs.

PMID- 15519688
TI  - Brain-derived neurotrophic factor acutely enhances tyrosine phosphorylation of
      the AMPA receptor subunit GluR1 via NMDA receptor-dependent mechanisms.
AB  - Brain-derived growth factor (BDNF) acutely regulates synaptic transmission and
      modulates hippocampal long-term potentiation (LTP) and long-term depression
      (LTD), cellular models of plasticity associated with learning and memory. Our
      previous studies revealed that BDNF rapidly increases phosphorylation of NMDA
      receptor subunits NR1 and NR2B in the postsynaptic density (PSD), potentially
      linking receptor phosphorylation to synaptic plasticity. To further define
      molecular mechanisms governing BDNF actions, we examined tyrosine phosphorylation
      of GluR1, the most well-characterized subunit of AMPA receptors. Initially, we
      investigated synaptoneurosomes that contain intact pre- and postsynaptic
      elements. Incubation of synaptoneurosomes with BDNF for 5 min increased tyrosine
      phosphorylation of GluR1 in a dose-dependent manner, with a maximal, 4-fold
      enhancement at 10 ng/ml BDNF. NGF had no effects, suggesting the specificity of
      BDNF actions. Subsequently, we found that BDNF elicited a maximal, 2.5-fold
      increase in GluR1 phosphorylation in the PSD at 250 ng/ml BDNF within 5 min,
      suggesting that BDNF enhances the phosphorylation through postsynaptic
      mechanisms. Activation of trkB receptors was critical as k252-a, an inhibitor of
      trk receptor tyrosine kinase, blocked the BDNF-activated GluR1 phosphorylation.
      In addition, AP-5 and MK 801, NMDA receptor antagonists, blocked BDNF enhancement
      of phosphorylation in synaptoneurosomes or PSDs. Conversely, NMDA, the specific
      receptor agonist, evoked respective 3.8- and 2-fold increases in phosphorylation
      in synaptoneurosomes and PSDs within 5 min, mimicking the effects of BDNF. These
      findings raise the possibility that BDNF modulates GluR1 activity via changes in
      NMDA receptor function. Moreover, incubation of synaptoneurosomes or PSDs with
      BDNF and ifenprodil, a specific NR2B antagonist, reproduced the results of AP-5
      and MK-801. Finally, coexposure of synaptoneurosomes or PSDs to BDNF and NMDA was
      not additive, suggesting that BDNF and NMDA activate the same tyrosine
      phosphorylation site(s) in GluR1. Our findings suggest that BDNF-mediated GluR1
      tyrosine phosphorylation potentially regulates synaptic plasticity
      postsynaptically through NR2B subunits of the NMDA receptor.

PMID- 15519689
TI  - Exposure to hexanal odor induces extraordinary Fos expression in the medial
      preoptic area and amygdala of Fyn tyrosine kinase-deficient mice.
AB  - Our previous study revealed that the odor of hexanal, which is derived from the
      wood chips used as bedding, influenced mouse maternal behavior and induced the
      neonatal death of Fyn-deficient (fyn(-/-)) pups born of fyn(-/-) parents. To
      clarify what regions of the brain are involved in this effect, we examined which
      brain regions of fyn(-/-) and Fyn-heterozygous (fyn(+/-)) females were activated
      by hexanal odor using Fos immunohistochemistry. Hexanal induced Fos
      immunoreactivity in the primary olfactory cortex and in the medial and central
      amygdala of both fyn(+/-) and fyn(-/-) mice. In fyn(-/-) females, hexanal also
      induced the activation of the medial preoptic area and the basolateral and
      posteriomedial cortical amygdala, which are known to be involved in the control
      of maternal and emotional behavior.

PMID- 15519690
TI  - Where do we go in the nucleus?

PMID- 15519691
TI  - Higher order chromatin architecture in the cell nucleus: on the way from
      structure to function.
AB  - The cell nucleus is a highly compartmentalized structure. In this review we
      describe controversial views on higher order chromatin organization from the
      level of higher order chromatin domains built up from folded chromatin fibers to
      the level of chromosome territories and the interchromatin compartment (IC),
      which harbors non-chromatin nuclear domains, such as interchromatin granule
      clusters (IGCs visualized in the electron microscope) or splicing factor
      containing speckles (visualized by fluorescence microscopy). Emphasis is laid on
      the definition and functional importance of a nuclear compartment located at the
      periphery of chromatin domains in direct contact with the IC, termed the
      perichromatin region (PR). Ongoing experiments to elucidate the topological
      relationships between PR and IC have provided new insights into the functional
      interplay between transcription and splicing. As an example, we discuss the
      structure and nuclear topology of perichromatin fibrils (FPs) contained in the PR
      and their functional interplay with IGCs/speckles. In addition we discuss the
      advantages and drawbacks of experimental approaches currently used to study
      nuclear architecture and function in fixed and living cells.

PMID- 15519692
TI  - Positioning the genome within the nucleus.
AB  - Higher eukaryotic genomes contain both housekeeping genes and genes of which the
      expression is restricted to a defined time and space. It is well established that
      a correlation exists between structural organization of the genome and gene
      expression control. The functional mechanisms underlying this correlation are
      still poorly understood. Here I describe several observations that are the basis
      of present concepts of genome organization and nuclear architecture related to
      functionality. Regarding the relationship between positioning and disturbed cell
      functionality, I describe observations showing that the proximity of selected
      gene loci is statistically correlated with their propensity for oncogenic
      translocations as well as observations of patterns occurring in neurodegenerative
      disorders where unstable repeats are translated into an expanded polyglutamine
      tract. Such observations underscore the importance to understand how genetic
      perturbations lead to the global reorganization of nuclear architecture,
      chromatin structure and widespread changes in gene expression.

PMID- 15519693
TI  - The nucleolus and transcription of ribosomal genes.
AB  - Ribosome biogenesis is a highly dynamic, steady-state nucleolar process that
      involves synthesis and maturation of rRNA, its transient interactions with non
      ribosomal proteins and RNPs and assembly with ribosomal proteins. In the few
      years of the 21st century, an exciting progress in the molecular understanding of
      rRNA and ribosome biogenesis has taken place. In this review, we discuss the
      recent results on the regulation of rRNA synthesis in relation to the functional
      organization of the nucleolus, and put an emphasis on the situation encountered
      in mammalian somatic cells.

PMID- 15519694
TI  - Internal organisation of the nucleus: assembly of compartments by macromolecular
      crowding and the nuclear matrix model.
AB  - Many and possibly all macromolecules in the nucleus are segregated into discrete
      compartments, but the current model that this is achieved by a fibrillar nuclear
      matrix which structures the nuclear interior and compartments is not consistent
      with all experimental observations, as reviewed here. New results are presented
      which suggest that macromolecular crowding forces play a crucial role in the
      assembly of at least two compartments, nucleoli and PML bodies, and an in vitro
      system in which crowding assembles macromolecular complexes into structures which
      resemble nuclear compartments is described. Crowding forces, which are strong in
      the nucleus due to the high macromolecule concentration (in the range of 100
      mg/ml), vastly increase the association constants of intermolecular interactions
      and can segregate different macromolecules into discrete phases. The model that
      they play a role in compartmentalisation of the nucleus is generally consistent
      with the properties of compartments, including their spherical or quasispherical
      form and their dynamic and mobile nature.

PMID- 15519696
TI  - Boundary elements and nuclear organization.
AB  - Functional compartmentalization of eukaryotic genomes is thought to be necessary
      for the proper regulation of gene expression. Chromatin insulators or boundary
      elements have been implicated in the establishment of this compartmentalization,
      as they may be involved in creating independent chromatin domains. Recent
      advances in understanding the mechanisms of insulator function suggest a role for
      boundary elements in determining transcriptional identity of chromatin and in
      organizing chromatin into structural compartments within the nucleus. Insulators
      may thus be involved in setting up topological chromatin domains associated with
      particular transcriptional states.

PMID- 15519695
TI  - Rearrangement of nuclear ribonucleoprotein (RNP)-containing structures during
      apoptosis and transcriptional arrest.
AB  - The aim of this paper is to review the data in the literature concerning
      ribonucleoprotein components during apoptosis, where a major rearrangement of
      RNPs takes place. In parallel with chromatin changes, the nucleoplasmic
      constituents (perichromatin fibrils; perichromatin granules; interchromatin
      granules and nuclear bodies) as well as the nucleoli aggregate into heterogeneous
      clusters called HERDS, in the interchromatin space. Later, these RNP-containing
      structures are extruded from the nucleus and leave the cell within cytoplasmic
      blebs. We propose also a role for HERDS as markers of irreversible
      transcriptional arrest.

PMID- 15519697
TI  - Heterochromatin structure and function.
AB  - Although heterochromatin has long been used as a model for studying chromatin
      condensation and heritable gene silencing, it is only relatively recently that
      detailed information has become available on the mechanisms that underlie its
      structure. Current evidence suggests that these operate on at least three
      different levels. A regular nucleosome array may facilitate packaging of the
      chromatin into a highly condensed configuration. Methylation of histone H3 lysine
      9 and lysine 27 generates heterochromatin marks that are recognised through
      binding of heterochromatin proteins such as HP1. Finally, very recent studies
      using genetic and biochemical approaches have indicated that the RNAi machinery
      plays an important role in the formation of heterochromatin.

PMID- 15519698
TI  - Nuclear export of RNA.
AB  - A defining feature of eukaryotic cells is the presence of a nuclear envelope
      separating transcription and DNA replication in the nucleus from the site of
      protein synthesis in the cytoplasm. The regulation of gene expression relies in
      part on the controlled exchange of molecules between these two compartments.
      Factors implicated in transcription regulation and DNA replication have to be
      imported into the nucleus, whereas RNAs produced in the nucleus have to be
      exported, either to fulfill their function in protein synthesis or to mature into
      functional particles. This review summarizes studies performed over the last 15
      years that led to the identification of cellular factors mediating nuclear export
      of the different classes of RNAs, including tRNAs, UsnRNAs, micro-RNAs, ribosomal
      RNAs and mRNAs. We also discuss recent evidence indicating that the nuclear
      transport step is intimately linked to RNA synthesis, processing and mRNP
      assembly, thus ensuring that only properly matured ribonucleoprotein (RNP)
      complexes reach the cytoplasm.

PMID- 15519699
TI  - The role of intranuclear lipids.
AB  - The presence of phospholipids as a component of chromatin is now well documented
      and many enzymes such as sphingomyelinase, sphingomyelin-synthase, reverse
      sphingomyelin-synthase and phosphatidylcholine-dependent phospholipase C have
      been described and characterised. Other lipids were demonstrated inside the
      nucleus especially plasmalogens and cholesterol. The chromatin phospholipids,
      comprising 10% of that present in the nucleus, show a different metabolism with
      respect to those present in either microsomes or in nuclear membranes; they
      increase also during the DNA duplication as shown during both liver regeneration
      and cell maturation. They appear localised near newly synthesized RNA in
      decondensed chromatin. Digestion of chromatin with RNase, but not with DNase,
      causes a loss of phospholipids. The composition of the chromatin phospholipid
      fraction shows an enrichment in sphingomyelin and phosphatidylserine. In this
      review the behaviour of single lipids in relation to cell proliferation, cell
      differentiation and apoptosis is described. Sphingomyelin, the lipid most
      represented in chromatin with respect to microsomes and nuclear membranes, is
      localised near to newly synthesized RNA, its presence appearing to protect RNA
      from RNase digestion. This effect is reversed by sphingomyelinase which digests
      sphingomyelin and, as a consequence, RNA may be hydrolysed. The amount of
      sphingomyelin is restored by sphingomyelin-synthase. Sphingomyelin increases
      during the differentiation process and apoptosis. An increase of sphingomyelinase
      with consequent decrease in sphingomyelin is observed at the beginning of S-phase
      of the cell cycle. A possible role in stabilising the DNA double helix is
      indicated. Phosphatidylserine behaves similarly during differentiation and
      appears to stimulate both RNA and DNA polymerases. Phosphatidylcholine is
      implicated in cell proliferation through the activation of intranuclear
      phosphatidylcholine-dependent phospholipase C and diacylglycerol production. The
      increase in diacylglycerol stimulates phosphatidylcholine synthesis through the
      major pathway from cytidyltriphosphate. An inhibition of phosphatidylcholine
      synthesis is responsible for the initiation of apoptosis. The presence of reverse
      sphingomyelin-synthase favours the formation of phosphatidylcholine, the donor of
      phosphorylcholine, from sphingomyelin. Little information has been reported for
      phospatidylethanolamine, but phosphtidylinositol appears to influence cell
      differentiation and proliferation. This last effect is due to the action of two
      enzymes: PI-PLCss1 having a role in the onset of DNA synthesis and PC-PLCgamma1
      acting in G2 transit. Phosphoinositides also may have an important role: in
      membrane-stripped nuclei isolated from mitogen stimulated cells a decrease in PIP
      and PIP2 followed by an increase in diacylglycerol and a translocation of protein
      kinase C inside the nucleus is observed. On the other hand, overexpression of the
      enzyme inositol polysphosphate-1-phosphatase reduced DNA synthesis by 50%.
      Nevertheless, an enhanced rate of phosphorylation has been demonstrated in cells
      induced to differentiate. These molecules probably favour RNA transcription,
      counteracting the inhibition of H1 on RNA polymerase II. Plasmalogens were
      demonstrated in the nucleus and their increase favours the increased activity of
      phosphatidylcholine-dependent phospholipase C when DNA synthesis starts.
      Moreover, two forms of cholesterol has been described in chromatin: one, a less
      soluble sphingomyelin-linked form and a free fraction. Cholesterol increases
      during liver regeneration, first as a linked fraction and then, when DNA
      synthesis starts, as a free fraction. The changes of these components have been
      summarised in relation to cell function in order to give an overview of their
      possible roles in the different phases of cell duplication and their influence on
      cell differentiation and during apoptosis. Finally, the relevance of these
      molecules as intranuclear signals is discussed and future directions are
      indicated in clarifying pathological process such as tumour cell transformation
      and the possibility in finding new therapeutic tools.

PMID- 15519700
TI  - Immunisation with aluminium-containing vaccine of a child with itching nodule
      following previous vaccination.
AB  - Vaccination of children with aluminium sensitisation against diphtheria and
      tetanus presents a problem, since vaccine without aluminium against these
      potentially serious infectious diseases is no longer available. This case report
      presents a 7-month-old boy who, after his second immunisation with DTaP-IPV,
      developed an itching injection site nodule. Before being tested for aluminium
      sensitisation, he was vaccinated again with DTaP-IPV without developing any
      reactions. This third vaccine dose was administered intramuscularly.

PMID- 15519701
TI  - Examination of the value of treatment of decompensated viral hepatitis patients
      by intentionally coinfecting them with an apathogenic IBDV and using the lessons
      learnt to seriously consider treating patients infected with HIV using the
      apathogenic hepatitis G virus.
AB  - Hepatitis virus infection persistent worldwide (approximately 600 m people)
      results in chronic hepatitis progressing to hepatocellular carcinoma (HCC) in
      many (approximately 1 m deaths/year). The review examines the usefulness of
      treating chronic viral hepatitis, including decompensated patients, by
      intentional coinfection with an attenuated infectious bursal disease virus (IBDV;
      apathogenic in man, stable at pH 2, orally administered). Learning lessons from
      the IBDV studies, the case is made to treat human immunodeficiency virus (HIV)
      infected patients (worldwide prevalence approximately 50 m people) by coinfecting
      with apathogenic hepatitis G virus (GBV-C). These ideas are reinforced by (i)
      eight out of ten studies reporting a beneficial effect of GBV-C viremia on HIV
      related mortality or response to therapy and (ii) the recent reports of improved
      or delayed survival of HIV patients, naturally coinfected with an apathogenic
      virus.

PMID- 15519702
TI  - Antibody persistence, PRP-specific immune memory, and booster responses in
      infants immunised with a combination DTPa-HBV-IPV/Hib vaccine.
AB  - A new single-injection combination vaccine against six diseases has been
      developed to accommodate the growing number of recommended paediatric vaccines. A
      pentavalent liquid diphtheria, tetanus, acellular pertussis (3-component),
      hepatitis B, and inactivated polio (types 1-3) combined vaccine (DTPa-HBV-IPV) is
      extemporaneously mixed with a lyophilized Haemophilus influenza type B (Hib)
      conjugate vaccine (polyribosyl-ribitol phosphate (PRP)-T) and given as a single
      injection. A cohort of 368 healthy infants was initially studied to evaluate the
      immunogenicity and reactogenicity of this hexavalent combination given as a
      primary course at 2, 4, and 6 months of age. At 15 months of age, from this
      cohort, 219 children received a booster dose of a licensed DTPa/Hib (PRP-T)
      vaccine to assess the booster response, while 70 received a challenge dose of
      unconjugated PRP (PRP) vaccine (to evaluate Hib-specific memory) plus a separate
      DTPa vaccine. Seven to 10 days following plain PRP challenge, anti-PRP geometric
      mean antibody concentrations (GMCs) had increased 13-fold to 5.67 microg/ml, and
      thirty days after conjugated PRP booster vaccination, anti-PRP antibody GMCs
      increased 102-fold. Both responses are indicative of immune memory. Vaccination
      was well tolerated following all primary and booster doses, although 10.5% of
      booster recipients experienced >50-mm local swelling at the site of DTPa
      vaccination. We conclude that DTPa-HBV-IPV/Hib is safe and immunogenic for
      primary vaccination, and that Hib-specific memory is induced by primary
      vaccination.

PMID- 15519703
TI  - Functional differences in IgG anti-polysaccharide antibodies elicited by
      immunization of mice with C3d versus ovalbumin conjugates of pneumococcal
      serotype 14 capsular polysaccharide.
AB  - We previously have shown that conjugation of C3d to pneumococcal serotype type 14
      capsular polysaccharide (PPS14) significantly enhances anti-PPS14 antibody
      production to a degree similar to that found when the T-dependent protein carrier
      ovalbumin (OVA) is coupled to PPS14. However, the anti-PPS14 antibody response to
      PPS14-C3d conjugates is characterized by less switching from IgM to IgG and lower
      serum concentrations of anti-PPS14 IgG after secondary immunization. To determine
      if these quantitative differences in anti-PPS14 IgG are accompanied by
      qualitative differences in the IgG anti-PPS14 antibodies, we performed several
      functional assays on serum IgG anti-PPS14 antibodies from mice immunized with
      PPS14-C3d or PPS14-OVA. Compared with antibodies elicited by immunization with
      PPS14-C3d, IgG anti-PPS14 antibodies produced after immunization with PPS14-OVA
      were found to have higher avidity and enhanced function as opsonins. Comparisons
      of avidity for IgG from serum samples obtained after primary and secondary
      immunization demonstrated a higher degree of avidity maturation after
      immunization with PPS14-OVA than with PPS14-C3d. These results suggest that PPS14
      C3d conjugates are unlikely to be more efficacious than PPS14 conjugate vaccines
      incorporating T-dependent protein carriers.

PMID- 15519704
TI  - Comparison of two combined vaccines against typhoid fever and hepatitis A in
      healthy adults.
AB  - A prospective, randomised, observer-blind, comparative study was performed in
      healthy adults with a new hepatitis A/typhoid combined vaccine, Viatim, and the
      marketed Hepatyrix vaccine. Both vaccines induced high levels of protective
      antibodies, but typhoid responses were higher and hepatitis A responses more
      rapid with Viatim compared with Hepatyrix. Both vaccines were well tolerated, no
      serious adverse events (SAEs) occurred, but more Viatim vaccinees had more mild
      or moderate local reactions (82.7%) than Hepatyrix (53.1%, p < 0.001). In this
      direct comparison Viatim induced more local reactions, but elicited a more rapid
      and higher immune response to both antigens than Hepatyrix.

PMID- 15519705
TI  - Effectiveness of Haemophilus influenzae type b vaccination against bacterial
      pneumonia in Colombia.
AB  - AIMS: To assess the effectiveness of a Hib vaccination program against X-ray
      defined bacterial pneumonia in children <2 years in Colombia. METHODS: 389 cases
      of radiologically confirmed pneumonia were recruited from hospitals in Bogota and
      Medellin, Colombia. Two controls per case, matched on age, sex, and socio
      economic level, were selected from children attending child health services at
      the hospitals where pneumonia cases were admitted. RESULTS: The risk of having X
      ray confirmed pneumonia decreased with each Hib dose received; the vaccine
      effectiveness was 47% (2-72%) among those receiving one dose; 52% for two doses
      received, and 55% for three doses. These effectiveness levels remained after
      adjusting for other factors associated with risk of pneumonia. CONCLUSIONS: This
      study indicates that trials may have underestimated the proportion of
      radiological pneumonia in the under 2s that is due to Hib. This suggests that the
      impact of the vaccination will be greater than expected if it can be extended to
      reach the poorest children, who are at the greatest risk.

PMID- 15519706
TI  - Anthrax capsule vaccine protects against experimental infection.
AB  - Efficacy of a poly-gamma-D-glutamic acid anthrax capsule vaccine was assessed in
      a mouse model of infection. Capsule by itself was protective against lethal
      challenge with a toxin(-), capsule(+) Bacillus anthracis strain. Conjugation of
      capsule to bovine serum albumin resulted in enhanced IgG anti-capsule antibodies
      measured by ELISA, but completely abrogated the protection. The protective
      unconjugated capsule vaccine elicited significantly higher IgM titers and opsonic
      activity than did the non-protective capsule conjugate. When tested against a
      fully virulent toxin(+), capsule(+) B. anthracis strain, neither capsule nor
      protective antigen alone was protective. However, the combination of the two
      protected against a lethal challenge. These results suggest that capsule may
      enhance the protection afforded by protective antigen vaccines against anthrax if
      opsonizing antibodies are produced. Surprisingly, some protection was also
      observed when protective antigen was conjugated to itself.

PMID- 15519707
TI  - Comparative sequence analysis of Bordetella bronchiseptica pertactin gene (prn)
      repeat region variants in swine vaccines and field isolates.
AB  - The product of the Bordetella bronchiseptica pertactin gene, prn, has been
      implicated as an adhesin and a protective immunogen in swine. Recent studies
      demonstrate prn sequence heterogeneity in swine isolates and vaccine strains
      within and surrounding the region 1 amino acid repeat GGXXP(n) and the region 2
      amino acid repeat PQP(n). However, only a few isolates have been evaluated.
      Allelic variation between vaccine strains and field isolates may affect vaccine
      efficacy, since region 2 is known to encode an immunodominant protective epitope.
      In the present study, the DNA and predicted amino acid sequences of the pertactin
      repeat regions from a collection of 81 recent swine field isolates and 5 vaccine
      strains from the United States were determined. Two region 1 variants and four
      region 2 variants, one of which has not been previously reported, were
      identified, comprising four pertactin types. Four vaccines are derived from
      strains with a region 1 variant identical to that found in the majority of field
      isolates. However, only two vaccines possess the most commonly identified
      sequence in region 2, while two others contain a variant found in only one other
      swine isolate. Ribotype analysis demonstrated that although vaccines containing
      the novel region 2 variant fall within the same major cluster as other common
      swine ribotypes, they are less closely related. No relationship was observed
      between pertactin type and ribotype.

PMID- 15519708
TI  - A liposomal peptide vaccine inducing CD8+ T cells in HLA-A2.1 transgenic mice,
      which recognise human cells encoding hepatitis C virus (HCV) proteins.
AB  - Virus specific T cell responses play an important role in resolving acute
      hepatitis C virus (HCV) infections. Using the HLA-A2.1 transgenic mouse model we
      investigated the potential of a liposomal peptide vaccine to prime a CD8(+) T
      cell response against 10 different HCV epitopes, relevant for human applications.
      We were able to demonstrate the induction of strong cytotoxic T cell responses
      and high numbers of IFN-gamma-secreting cells, which persisted at high levels for
      at least 3 months. Co-integrating CpG oligonucleotides into liposomes further
      increased the number of IFN-gamma-secreting cells by 2-10-fold for most epitopes
      tested. The frequency of specific cells was further analysed with chimeric A2
      tetramers bearing the NS31073-1081 epitope and was estimated at 2-23% of the
      CD8(+) T cell population. Importantly, mouse effector cells, specific for this
      epitope, were also capable of lysing a human target cell line expressing HCV
      proteins. This finding and the specific protection observed in challenge
      experiments with recombinant vaccinia virus expressing HCV sequences emphasise
      the biological relevance of the vaccine-induced immune response. In conclusion,
      such liposome formulations represent a safe and promising strategy to stimulate
      the CD8(+) T cell against HCV.

PMID- 15519709
TI  - Foot-and-mouth disease polyvalent oil vaccines inoculated repeteadly in cattle do
      not induce detectable antibodies to non-structural proteins when evaluated by
      various assays.
AB  - The use of foot-and-mouth disease (FMD) vaccines that do not induce antibodies
      against non-structural proteins (NSP) is extremely relevant for the demonstration
      of regions "free of FMDV infection" and control strategies. In this study cattle
      were primed and boosted with five doses of oil vaccines containing high antigenic
      payloads on days 0, 90, 130, 160 and 200. The serological response against NSP
      was measured using four commercially available assays: two 3ABC-ELISAs; one 3B
      ELISA (and complementary 3A-ELISA) and an enzyme-immunotransfer blot assay
      (EITB). Additionally, locally produced NSP antibodies detection reagents and VIAA
      antibodies were evaluated. A high level of specific immune response against
      vaccine strains was shown. After four doses of vaccine, non-reactive animals were
      detected by any of the NSP assays. After the fifth immunization, 2 of 17 animals
      were reactive in one ELISA kit, but these samples proved negative by confirmatory
      tests. Antibodies against NSP were not detected in single dose immunized cattle.
      The principle of the NSP-ELISA used as a screening test for large sero-surveys in
      South America is established and this paper emphasizes the importance of using
      vaccines that have demonstrated no interference with NSP antibodies detection
      assays.

PMID- 15519710
TI  - The protective effect of a Schistosoma japonicum Chinese strain 23 kDa plasmid
      DNA vaccine in pigs is enhanced with IL-12.
AB  - The schistosome integral membrane protein Sm/Sj23 was initially shown to induce
      protection in mice as a synthetic peptide vaccine and further, as a plasmid DNA
      vaccine to induce protection in mice, sheep and water buffalo. In this study we
      asked if we could induce protection against challenge infection in pigs against
      Schistosoma japonicum by vaccinating them with a plasmid DNA vaccine encoding the
      S. japonicum Chinese strain 23 kDa membrane protein. Further, we asked if we
      could enhance protective efficacy of this vaccine by the addition of IL-12. We
      compared vaccination with SjC23 plasmid DNA alone or with IL-12 plasmid DNA in
      pigs. Pigs were immunized three times at three weekly intervals. Thirty Chinese
      Songjang native pigs were divided into three groups. In group A, each pig was
      immunized with 500 microg of SjC23 plasmid DNA by intramuscular (i.m.) injection
      in both buttocks. In group B each pig was immunized with 500 microg of SjC23
      plasmid DNA, and 500 microg of each of pcDNA3.1-p35 and 500 microg of pcDNA3.1
      p40 DNA by i.m. injection. In group C each pig was immunized with 500 microg of
      pcDNA3.1 as the control. Thirty days post-vaccination, pigs were challenged with
      S. japonicum cercariae and adult and egg burdens and granuloma size determined 45
      days post-challenge. The results showed that worm reduction rates in SjC23 group
      compared with control group were 29.2% and in the SjC23 + IL-12 group reduced
      58.6%. Similarly the female worm reduction rates were 50.8 and 58.8%, the hepatic
      egg reduction rates were 48.2 and 56.4%, and the mean square measure reduction
      rates of hepatic egg granulomas were 48.6 and 44.4%, the mean diameter reduction
      rates of granulomas were 27.6 and 22.8% in pigs vaccinated with SjC23 or SjC23 +
      IL-12 compared to plasmid vaccinated pigs, respectively. Analysis of sera from
      pigs vaccinated with SjC23 showed that 4 of 10 pigs had anti-Sj23 antibody
      responses; with 5 of 10 pigs positive for anti-Sj23 in the SjC23+IL-12 group.
      These results suggest that vaccination with Sj23 DNA vaccine induces not only a
      significant reduction in worm and egg burdens, but also significantly reduces the
      size of egg granulomas, thus is also anti-pathology.

PMID- 15519711
TI  - Preventive vaccines against bioterrorism: evaluation of efficacy and safety.
AB  - This paper discusses the US Food and Drug Administration's approach to evaluation
      of vaccines in general, and vaccines against diseases of bioterrorism in
      particular. We summarize the scientific bases for development and approval of
      vaccines and then discuss specific issues regarding vaccines against disease
      organisms that could potentially be used as weapons of bioterrorism.

PMID- 15519712
TI  - Does influenza vaccination exacerbate asthma in children?
AB  - BACKGROUND: The risks of influenza vaccination in asthmatic children are still
      being discussed. Especially, the risk that influenza vaccination may exacerbate
      asthma is an issue in this debate. METHODS: We conducted a randomised double
      blind placebo-controlled trial in 696 children 6-18 years of age with asthma
      recruited in general practice during two influenza seasons, 1999-2000 and 2000
      2001. Children participated for only one season. During the first week after
      vaccination, participants recorded local, influenza like and asthma symptoms as
      well as use of medication, health care use and absenteeism. RESULTS: Except for
      cough during the day in the first season, favouring placebo, there were no
      differences indicating that vaccination exacerbates asthma. CONCLUSIONS:
      Influenza vaccination does not seem to exacerbate asthma.

PMID- 15519713
TI  - On the road to a tumor cell vaccine: 20 years of cellular immunotherapy.
AB  - Cellular immunotherapy (CI), as we now know it, began in the early 1980s with the
      use of lymphokine-activated killer cells (LAK) and progressed to the use of the
      immunologically specific, tumor-infiltrating lymphocytes (TIL). TIL were shown to
      be particularly effective against melanoma and it was in these trials that we
      learned the importance of immunologic specificity for tumor. With the
      identification and characterization of tumor antigens recognized by TIL, we now
      see the use of these antigens in various forms constituting vaccines.
      Investigators are using tumor antigens alone or in combination with dendritic
      cells (DCs), the body's most efficient and powerful antigen-presenting cell.
      Therapies are being delivered to many patients with different types of cancer in
      order to combat bulky disease, eliminate micro-metastatic disease, and provide a
      memory mechanism to fight tumor recurrence. This review will detail the past 18
      years and present the developments that have been made in this therapy. Many
      believe that with continued development, immunotherapy will provide a fourth
      modality of cancer therapy.

PMID- 15519714
TI  - Immune responses to a DNA/protein vaccination strategy against Staphylococcus
      aureus induced mastitis in dairy cows.
AB  - The fibronectin binding protein (FnBP) and clumping factor A (ClfA) of
      Staphylococcus aureus are important proteins involved in the pathogenesis of
      staphylococcal bovine mastitis. These antigens were the targets of a DNA and
      protein vaccination strategy against S. aureus induced mastitis in dairy cows.
      The DNA vaccine comprised the bicistronic plasmid (pCI-D(1)D(3)-IRES-ClfA) that
      encoded the fusion of two sequences, (D1(21-34); D3(20-33)) from the fibronectin
      binding motifs of FnBP and a fragment from ClfA (aa 221-550) of S. aureus 8325-4
      separated by an Internal Ribosomal Entry Site (IRES) sequence. In addition, the
      vaccine contained the plasmid encoding the bovine granulocyte-macrophage-colony
      stimulatory factor gene (pCI-bGM-CSF). Four, 7-month pregnant heifers were
      immunized twice with the DNA vaccine and boosted once with recombinant D(1)D(3)
      and ClfA proteins while four others were not immunized. The immunization induced
      lymphoproliferative responses and functional antibodies against D(1)D(3) and ClfA
      antigens. Three weeks after calving, three mammary quarters of each vaccinated
      and non-vaccinated cow were challenged with 900 CFU/each of S. aureus Newbould
      305. The fourth quarter received saline only. Serum haptoglobin levels, cardiac
      rhythm and the body temperature of vaccinated cows during the 24-72 h post
      challenge were lower than in non-vaccinated animals. At 21 days post-challenge,
      bacteria were present in 5 of the vaccinated and 11 of the control challenged
      quarters. The bacteria averaged 1.4 and 3.3 log(10) CFU/ml of milk from
      vaccinated and control cows respectively. In summary, DNA-protein vaccination
      against FnBP and ClfA of S. aureus caused both lymphoproliferative and humoral
      immune responses that provided partial protection of mammary gland from
      staphylococcal mastitis and better post-challenge conditions in vaccinated cows.

PMID- 15519715
TI  - Aquatic microcosm assessment of the effects of tylosin on Lemna gibba and
      Myriophyllum spicatum.
AB  - Tylosin is a macrolide antibiotic commonly used for therapeutic treatment and
      prophylaxis in livestock. As part of a larger ecotoxicological study, the
      potential phytotoxic effects of tylosin on the rooted macrophyte Myriophyllum
      spicatum and the floating macrophyte Lemna gibba were assessed under semi-field
      conditions using 15 12 000-L microcosms. Concentrations of 0, 10, 30, 300
      microg/L (n = 3), and 600, 1000, and 3000 microg/L (n = 1) were evaluated as part
      of separate ANOVA and regression analyses over an exposure period of 35 days.
      Fate of tylosin was monitored over time in the highest three treatments, where
      dissipation followed pseudo-first order kinetics with associated half-lives
      ranging from 9 to 10 days. For both M. spicatum and L. gibba, tylosin was found
      to cause no biologically significant changes to any endpoint assessed compared to
      controls at a Type I error rate of 0.1. However, subsequent power analyses
      revealed that there was generally insufficient power to declare that there were
      no significant differences at a Type II error rate of 0.2. Conclusions concerning
      biologically significant impacts were therefore further assessed based on other
      statistical criteria including comparisons of percent differences between
      replicated treatments and controls, minimum significant and minimum detectable
      differences, and coefficients of variation. Based on these criteria, at an
      ecological effect size of >20% change, tylosin was concluded to elicit no
      biologically or ecologically significant toxicity to M. spicatum or L. gibba. A
      hazard quotient assessment indicated that tylosin poses little risk to either
      species of macrophyte, with an HQ value calculated to be nearly three orders of
      magnitude below 1 (0.002).

PMID- 15519716
TI  - Monitoring and modelling of biosphere/atmosphere exchange of gases and aerosols
      in Europe.
AB  - Monitoring and modelling of deposition of air pollutants is essential to develop
      and evaluate policies to abate the effects related to air pollution and to
      determine the losses of pollutants from the atmosphere. Techniques for monitoring
      wet deposition fluxes are widely applied. A recent intercomparison experiment,
      however, showed that the uncertainty in wet deposition is relatively high, up to
      40%, apart from the fact that most samplers are biased because of a dry
      deposition contribution. Wet deposition amounts to about 80% of the total
      deposition in Europe with a range of 10-90% and uncertainty should therefore be
      decreased. During recent years the monitoring of dry deposition has become
      possible. Three sites have been operational for 5 years. The data are useful for
      model development, but also for model evaluation and monitoring of progress in
      policy. Data show a decline in SO(2) dry deposition, whereas nitrogen deposition
      remained constant. Furthermore, surface affinities for pollutants changed leading
      to changes in deposition. Deposition models have been further developed and
      tested with dry deposition measurements and total deposition measurements on
      forests as derived from throughfall data. The comparison is reasonable given the
      measurement uncertainties. Progress in ozone surface exchange modelling and
      monitoring shows that stomatal uptake can be quantified with reasonable accuracy,
      but external surface uptake yields highest uncertainty.

PMID- 15519717
TI  - Concentrations and compositions of organochlorine contaminants in sediments,
      soils, crustaceans, fishes and birds collected from Lake Tai, Hangzhou Bay and
      Shanghai city region, China.
AB  - Contamination by persistent organochlorines (OCs), such as DDTs,
      hexachlorocyclohexane isomers (HCHs), chlordane compounds (CHLs),
      hexachlorobenzene (HCB) and polychlorinated biphenyls (PCBs) were examined in
      sediments, soils, fishes, crustaceans, birds, and aquaculture feed from Lake Tai,
      Hangzhou Bay, and in the vicinity of Shanghai city in China during 2000 and 2001.
      OCs were detected in all samples analyzed, and DDT and its metabolites were the
      predominant contaminants in most sediments, soils and biota. Concentrations of
      p,p'-DDT and ratio of p,p'-DDT to SigmaDDTs were significantly higher in marine
      fishes than those in freshwater fishes. While the use of DDTs has been officially
      banned in China since 1983, these results indicate a recent input of technical
      DDTs into the marine environment around Hangzhou Bay. Comparison of
      organochlorine concentrations in fishes collected from Lake Tai and Hangzhou Bay
      suggests the presence of local sources of HCHs, chlordanes and PCBs at Lake Tai.
      Higher proportions of penta- and hexa-PCB congeners in fishes at Lake Tai may
      suggest the use of highly chlorinated PCB product, such as PCB(5), around this
      lake. To our knowledge, this is a first comprehensive study to examine the
      present status of organochlorine contamination in various environmental media,
      such as sediments, soils and wildlife, in China.

PMID- 15519718
TI  - Modelling the fate of sulphur-35 in crops. 1. Calibration data.
AB  - Gas-cooled nuclear power plants in the UK release sulphur-35 during their routine
      operation. The gas is in the form of COS which can be readily assimilated by
      vegetation. It is therefore necessary to be able to model the uptake of such
      releases in order to quantify any potential contamination of the food chain. To
      develop such models experimental data are required. A series of experiments was
      undertaken to determine the rate of deposition, the partition and subsequent loss
      of sulphur-35 in crops exposed to CO(35)S. The mass normalised deposition rate
      was similar for the range of crops tested, while the partition of the (35)S
      paralleled the growth of crop components. There was no significant loss of
      radioactivity other than that expected from radioactive decay.

PMID- 15519719
TI  - Modelling the fate of sulphur-35 in crops. 2. Development and validation of the
      CROPS-35 model.
AB  - Gas-cooled nuclear power plants in the UK release sulphur-35 during their routine
      operation, which can be readily assimilated by vegetation. It is therefore
      necessary to be able to model the uptake of such releases in order to quantify
      any potential contamination of the food chain. A model is described which
      predicts the concentration of (35)S in crop components following an aerial
      gaseous release. Following deposition the allocation to crop components is
      determined by an export function from a labile pool, the leaves, to those
      components growing most actively post exposure. The growth rates are determined
      by crop growth data, which is also used to determine the concentration. The loss
      of activity is controlled by radioactive decay only. The paper describes the
      calibration and the validation of the model. To improve the model, further
      experimental work is required particularly on the export kinetics of (35)S. It
      may be possible to adapt such a modelling approach to the prediction of crop
      content for gaseous releases of (3)H and (14)C from nuclear facilities.

PMID- 15519720
TI  - Intrinsic and induced isoproturon catabolic activity in dissimilar soils and
      soils under dissimilar land use.
AB  - The catabolic activity with respect to the systemic herbicide isoproturon was
      determined in soil samples by (14)C-radiorespirometry. The first experiment
      assessed levels of intrinsic catabolic activity in soil samples that represented
      three dissimilar soil series under arable cultivation. Results showed average
      extents of isoproturon mineralisation (after 240 h assay time) in the three soil
      series to be low. A second experiment assessed the impact of addition of
      isoproturon (0.05 microg kg(-1)) into these soils on the levels of catabolic
      activity following 28 days of incubation. Increased catabolic activity was
      observed in all three soils. A third experiment assessed levels of intrinsic
      catabolic activity in soil samples representing a single soil series managed
      under either conventional agricultural practice (including the use of
      isoproturon) or organic farming practice (with no use of isoproturon). Results
      showed higher (and more consistent) levels of isoproturon mineralisation in the
      soil samples collected from conventional land use. The final experiment assessed
      the impact of isoproturon addition on the levels of inducible catabolic activity
      in these soils. The results showed no significant difference in the case of the
      conventional farm soil samples while the induction of catabolic activity in the
      organic farm soil samples was significant.

PMID- 15519721
TI  - The effects of perennial ryegrass and alfalfa on microbial abundance and
      diversity in petroleum contaminated soil.
AB  - Enhanced rhizosphere degradation uses plants to stimulate the rhizosphere
      microbial community to degrade organic contaminants. We measured changes in
      microbial communities caused by the addition of two species of plants in a soil
      contaminated with 31,000 ppm of total petroleum hydrocarbons. Perennial ryegrass
      and/or alfalfa increased the number of rhizosphere bacteria in the hydrocarbon
      contaminated soil. These plants also increased the number of bacteria capable of
      petroleum degradation as estimated by the most probable number (MPN) method. Eco
      Biolog plates did not detect changes in metabolic diversity between bulk and
      rhizosphere samples but denaturing gradient gel electrophoresis (DGGE) analysis
      of PCR-amplified partial 16S rDNA sequences indicated a shift in the bacterial
      community in the rhizosphere samples. Dice coefficient matrices derived from DGGE
      profiles showed similarities between the rhizospheres of alfalfa and perennial
      ryegrass/alfalfa mixture in the contaminated soil at week seven. Perennial
      ryegrass and perennial ryegrass/alfalfa mixture caused the greatest change in the
      rhizosphere bacterial community as determined by DGGE analysis. We concluded that
      plants altered the microbial population; these changes were plant-specific and
      could contribute to degradation of petroleum hydrocarbons in contaminated soil.

PMID- 15519722
TI  - Quantifying the role of forest soil and bedrock in the acid neutralization of
      surface water in steep hillslopes.
AB  - The role of soil and bedrock in acid neutralizing processes has been difficult to
      quantify because of hydrological and biogeochemical uncertainties. To quantify
      those roles, hydrochemical observations were conducted at two hydrologically well
      defined, steep granitic hillslopes in the Tanakami Mountains of Japan. These
      paired hillslopes are similar except for their soils; Fudoji is leached of base
      cations (base saturation <6%), while Rachidani is covered with fresh soil (base
      saturation >30%), because the erosion rate is 100-1000 times greater. The results
      showed that (1) soil solution pH at the soil-bedrock interface at Fudoji (4.3)
      was significantly lower than that of Rachidani (5.5), (2) the hillslope discharge
      pH in both hillslopes was similar (6.7-6.8), and (3) at Fudoji, 60% of the base
      cations leaching from the hillslope were derived from bedrock, whereas only 20%
      were derived from bedrock in Rachidani. Further, previously published results
      showed that the stream pH could not be predicted from the acid deposition rate
      and soil base saturation status. These results demonstrate that bedrock plays an
      especially important role when the overlying soil has been leached of base
      cations. These results indicate that while the status of soil acidification is a
      first-order control on vulnerability to surface water acidification, in some
      cases such as at Fudoji, subsurface interaction with the bedrock determines the
      sensitivity of surface water to acidic deposition.

PMID- 15519723
TI  - Mercury burdens in Chinese mitten crabs (Eriocheir sinensis) in three tributaries
      of southern San Francisco Bay, California, USA.
AB  - Chinese mitten crabs (Eriocheir sinensis), endemic to Asia, were first reported
      in the San Francisco Bay in 1992. They are now established in nearly all San
      Francisco Bay tributaries. These crabs accumulate more metals, such as mercury,
      than crustaceans living in the water column. Because their predators include
      fish, birds, mammals and humans, their mercury burdens have an exceptional
      potential to impact the ecosystem and public health. We sought to elucidate the
      potential threat of mitten crab mercury burdens in three adjacent streams in
      southern San Francisco Bay, one of which is known to be contaminated with
      mercury. Mitten crabs had hepatopancreas concentrations of total mercury and
      methylmercury that did not differ among streams. The maximum burden we measured
      was below the action level of 1 ppm recommended by the USEPA. Hepatopancreas
      concentrations of methylmercury declined with increasing crab size, suggesting a
      mechanism for mercury excretion and that predators might reduce mercury exposure
      if they select larger crabs. Because mercury may be heterogeneously distributed
      among tissues, estimation of the impacts of crab mercury burdens on the
      environment requires more data on the feeding preferences of predators.

PMID- 15519724
TI  - Accumulation of butyl- and phenyltin compounds in starfish and bivalves from the
      coastal environment of Korea.
AB  - Triphenyltin (TPT) and tributyltin (TBT) concentrations were determined in two
      starfish species (Asteria pectinifera and Asterias amurensis), bivalves
      (Crassostrea gigas or Mytilus edulis), and seawater samples from sites around the
      coasts of Korea. Both TPT and TBT concentrations in starfish ranged from 8 to
      1560 ng/g and from <2 to 797 ng/g as Sn on a dry weight basis, respectively. TPT
      concentration accounted for 75.4% and 86.4% of total phenyltin concentration in
      A. pectinifera and A. amurensis, respectively, while monobutyltin, a degradation
      product of TBT, accounted for 86.3% and 57.2% of total butyltin, respectively.
      Triphenyltin concentrations in A. pectinifera were significantly correlated to
      water and bivalve TPT concentrations, which implies that dietary uptake of TPT
      from contaminated prey as well as direct uptake from surrounding water contribute
      to TPT body residues in the starfish. Starfish could be target organisms for
      monitoring TPT compound in the marine environment, due to their high accumulation
      and low degradation capacity towards TPT.

PMID- 15519725
TI  - Brominated flame retardants in Alburnus alburnus from Cinca River Basin (Spain).
AB  - Thirty-two bleak fish (Alburnus alburnus) from three places along the Spanish
      River Cinca, a tributary of Ebro River, were collected for polybrominated
      diphenyl ether (PBDE) and hexabromocyclododecane (HBCD) determinations. Sampling
      sites corresponded to up- and downstream from Monzon, a heavily industrialized
      town draining to the river. Four different PBDE congeners (BDE-47, -153, -154 and
      -183) and HBCD were found at levels ranging from not detected (nd) to 573 ng/g
      wet weight for total PBDEs and from nd to 1643 ng/g wet weight for HBCD. The
      lowest values were found upstream of the industrialized area. Concentrations in
      fish were compared with previous data in sediment samples collected at the same
      sampling sites, and large fish to sediment ratios for these brominated compounds
      indicate that they are highly bioavailable. Moreover, PBDE and HBCD
      concentrations are correlated with fish length and weight indicating the
      bioaccumulation of these contaminants.

PMID- 15519726
TI  - Temporal trends of organochlorine contamination in Black Guillemots in Iceland
      from 1976 to 1996.
AB  - The levels of several different persistent organochlorines (OCs) in Black
      Guillemots Cepphus grylle, collected during the summers of 1976-1996 at
      Breioafjorour in W-Iceland, were investigated. The levels of about 40 different
      organochlorines (PCBs, DDTs, chlordanes, toxaphenes, HCH, HCB) were compared with
      respect to age, sex, fat content, and year of collection. The levels of PCBs
      correlated very closely with those of DDE, indicating long-range transport as the
      major source of these contaminants in Iceland, with the ratio PCBs/DDE mostly in
      the range of 2-5. Unlike the Gyrfalcon Falco rusticolus, the organochlorine
      levels did not seem to accumulate substantially with age, neither in males nor
      females. The variation in the levels of OCs at the age of 2 years was even
      greater than the variation in OC levels over an age range of 12 years. In
      immature birds the levels of PCBs, DDE, HCB and beta-HCH declined very slowly
      (T(1/2) from 12 to 20 years) over the years 1976-1996, whereas the levels of
      alpha-HCH and p,p'-DDT declined much faster. The levels of trans-nonachlor, alpha
      chlordane, gamma-chlordane, oxychlordane, and toxaphene did not correlate with
      the year of collection. As the Black Guillemot is mostly a resident seabird,
      feeding mainly on small fish and invertebrates, this investigation should give a
      good indication of the temporal trends of organochlorine pollution at
      Breioafjorour, Iceland, during this 20 year period and is likely to reflect
      baseline trends in the marine environment of the North-Atlantic Ocean.

PMID- 15519727
TI  - Evaluation of photolysis and hydrolysis of atrazine and its first degradation
      products in the presence of humic acids.
AB  - Relative importance of hydrolysis and photolysis of atrazine and its degradation
      products in aqueous solutions with dissolved humic acids (HA) has been assessed
      under exposure to sunlight and under UV irradiation. Quantum yield for direct
      photolysis of atrazine at 254 nm was 0.037 mol photon(-1), the reaction order was
      0.8. Atrazine, desethylatrazine and desisopropylatrazine converted to their 2
      hydroxy analogs with rate constants 0.02-0.08 min(-1) in clear solutions, while
      addition of HA (300 mg L(-1)) caused a 10-fold increase in rate constants.
      Hydroxyatrazine was not degraded. No evidence of photo-Fenton reaction was found.
      Under exposure to solar light, atrazine, desethylatrazine and
      desisopropylatrazine were converted to 2-hydroxy analogs only at pH 2 because of
      acid hydrolysis and possible contribution of photolysis. At lower HA
      concentration, only their light-shielding effect was noticed, while at higher
      concentrations, HA-catalysed hydrolysis prevailed. Hydroxyatrazine concentration
      diminished at all pH values in solutions without HA exposed to sunlight.

PMID- 15519728
TI  - Differential swimming performance of two natricine snakes exposed to a
      cholinesterase-inhibiting pesticide.
AB  - Environmental contaminants have direct effects on organisms at the molecular,
      cellular, and tissue levels, but the net results of these sub-organismal effects
      are only consequential to exposed populations if they alter organism-level traits
      that ultimately influence fitness (e.g., growth, locomotor performance,
      reproduction, and survival). Here, we explore the possibility that the swimming
      performance of neonate black swamp snakes (Seminatrix pygaea) and diamondback
      water snakes (Nerodia rhombifer) may be affected by exposure to carbaryl (2.5 and
      5.0 mg/L). The highest concentration of carbaryl caused greater reductions in
      swim velocity in S. pygaea than in N. rhombifer. Most individuals recovered from
      the effects of carbaryl on swimming performance within 96 h, but recovery was
      significantly slower in S. pygaea than in N. rhombifer. We hypothesize that the
      sensitivity of S. pygaea may arise from its highly permeable integument compared
      to other natricines. Our findings suggest that performance can serve as an
      ecologically relevant response to contaminant exposure in reptiles and warrants
      further study.

PMID- 15519729
TI  - Clonal variation in heavy metal accumulation and biomass production in a poplar
      coppice culture. II. Vertical distribution and phytoextraction potential.
AB  - Short rotation coppice cultures (SRC) are intensively managed, high-density
      plantations of multi-shoot trees. In April 1996, an SRC field trial with 17
      different poplar clones was established in Boom (Belgium) on a former waste
      disposal site. In December 1996 and January 2001, all shoots were cut back to a
      height of 5 cm to create a coppice culture. For six clones, wood and bark were
      sampled at the bottom, middle and top of a shoot in August and November 2002. No
      significant height effect of metal concentration was found, but for wood, metal
      concentrations generally increased toward the top of the shoot in August, and
      decreased toward the top of the shoot in November. Phytoextraction potential of a
      clone was primarily determined by metal concentration and by biomass production.
      Shoot size and number of shoots per stool were less important, as a high biomass
      production could be achieved by producing a few large shoots or many smaller
      shoots. Clone Fritzi Pauley accumulated 1.4 kg ha(-1) of Al over two years;
      Wolterson and Balsam Spire showed a relatively high accumulation of Cd and Zn,
      i.e. averaging, respectively 47 and 57 g ha(-1) for Cd and 2.4 and 2.0 kg ha(-1)
      for Zn over two years.

PMID- 15519730
TI  - Physiological and foliar symptom response in the crowns of Prunus serotina,
      Fraxinus americana and Acer rubrum canopy trees to ambient ozone under forest
      conditions.
AB  - The crowns of five canopy dominant black cherry (Prunus serotina Ehrh.), five
      white ash (Fraxinus americana L.), and six red maple (Acer rubrum L.) trees on
      naturally differing environmental conditions were accessed with scaffold towers
      within a mixed hardwood forest stand in central Pennsylvania. Ambient ozone
      concentrations, meteorological parameters, leaf gas exchange and leaf water
      potential were measured at the sites during the growing seasons of 1998 and 1999.
      Visible ozone-induced foliar injury was assessed on leaves within the upper and
      lower crown branches of each tree. Ambient ozone exposures were sufficient to
      induce typical symptoms on cherry (0-5% total affected leaf area, LAA), whereas
      foliar injury was not observed on ash or maple. There was a positive correlation
      between increasing cumulative ozone uptake (U) and increasing percent of LAA for
      cherry grown under drier site conditions. The lower crown leaves of cherry showed
      more severe foliar injury than the upper crown leaves. No significant differences
      in predawn leaf water potential (psi(L)) were detected for all three species
      indicating no differing soil moisture conditions across the sites. Significant
      variation in stomatal conductance for water vapor (g(wv)) was found among
      species, soil moisture, time of day and sample date. When comparing cumulative
      ozone uptake and decreased photosynthetic activity (P(n)), red maple was the only
      species to show higher gas exchange under mesic vs. drier soil conditions (P <
      0.05). The inconsistent differences in gas exchange response within the same
      crowns of ash and the uncoupling relationship between g(wv) and P(n) demonstrate
      the strong influence of heterogeneous environmental conditions within forest
      canopies.

PMID- 15519731
TI  - Stochastic analysis to assess the spatial distribution of groundwater nitrate
      concentrations in the Po catchment (Italy).
AB  - A large database including temporal trends of physical, ecological and socio
      economic data was developed within the EUROCAT project. The aim was to estimate
      the nutrient fluxes for different socio-economic scenarios at catchment and
      coastal zone level of the Po catchment (Northern Italy) with reference to the
      Water Quality Objectives reported in the Water Framework Directive (WFD
      2000/60/CE) and also in Italian legislation. Emission data derived from different
      sources at national, regional and local levels are referred to point and non
      point sources. While non-point (diffuse) sources are simply integrated into the
      nutrient flux model, point sources are irregularly distributed. Intensive farming
      activity in the Po valley is one of the main Pressure factors Driving groundwater
      pollution in the catchment, therefore understanding the spatial variability of
      groundwater nitrate concentrations is a critical issue to be considered in
      developing a Water Quality Management Plan. In order to use the scattered point
      source data as input in our biogeochemical and transport models, it was necessary
      to predict their values and associated uncertainty at unsampled locations. This
      study reports the spatial distribution and uncertainty of groundwater nitrate
      concentration at a test site of the Po watershed using a probabilistic approach.
      Our approach was based on geostatistical sequential Gaussian simulation used to
      yield a series of stochastic images characterized by equally probable spatial
      distributions of the nitrate concentration across the area. Post-processing of
      many simulations allowed the mapping of contaminated and uncontaminated areas and
      provided a model for the uncertainty in the spatial distribution of nitrate
      concentrations.

PMID- 15519732
TI  - Absorption of decabromodiphenyl ether and other organohalogen chemicals by grey
      seals (Halichoerus grypus).
AB  - An input-output balance study was performed for polybrominated diphenyl ethers,
      polychlorinated biphenyls and some organochlorine pesticides on three captive,
      juvenile grey seals (Halichoerus grypus). The animals were fed a diet of herring
      for six months, during the last three months of which this study was performed. A
      supplement of decabromodiphenyl ether was included in the diet during the second
      month of the study. Consistently high absorption (>89%) was observed for all of
      the chemicals studied, whereas work on other animals has generally shown high
      (>80%) net absorption at log K(OW) < approximately 6, dropping towards higher log
      K(OW), and very low absorption of decabromodiphenyl ether. The half-life of
      decabromodiphenyl ether in blood was estimated to be between 8.5 and 13 days.
      Measurable concentrations of decabromodiphenyl ether were detected in seal
      blubber at the end of the study, indicating that this chemical can be stored in
      adipose and may bioaccumulate. Current understanding of the mechanism of
      absorption of organohalogen chemicals and the potential for accumulation of
      decabromodiphenyl ether will need reassessing in the light of these results.

PMID- 15519733
TI  - Spray irrigation of landfill leachate: estimating potential exposures to workers
      and bystanders using a modified air box model and generalised source term.
AB  - Generalised source term data from UK leachates and a probabilistic exposure model
      (BPRISC(4)) were used to evaluate key routes of exposure from chemicals of
      concern during the spraying irrigation of landfill leachate. Risk estimates
      secured using a modified air box model are reported for a hypothetical worker
      exposed to selected chemicals within a generalised conceptual exposure model of
      spray irrigation. Consistent with pesticide spray exposure studies, the key risk
      driver is dermal exposure to the more toxic components of leachate. Changes in
      spray droplet diameter (0.02-0.2 cm) and in spray flow rate (50-1000 l/min) have
      little influence on dermal exposure, although the lesser routes of aerosol
      ingestion and inhalation are markedly affected. The risk estimates modelled using
      this conservative worst case exposure scenario are not of sufficient magnitude to
      warrant major concerns about chemical risks to workers or bystanders from this
      practice in the general sense. However, the modelling made use of generic
      concentration data for only a limited number of potential landfill leachate
      contaminants, such that individual practices may require assessment on the basis
      of their own merits.

PMID- 15519734
TI  - Involvement of mitochondrial- and Fas-mediated dual mechanism in CoCl2-induced
      apoptosis of rat PC12 cells.
AB  - Hypoxic/ischemic condition induces neuronal apoptotic events, which consequently
      lead to neuronal cell death. However, its specific mechanistic pathways remain
      obscure. Cobalt chloride (CoCl(2)) could mimic the hypoxic condition including
      the production of reactive oxygen species (ROS). In this report, we investigated
      the signal pathway of CoCl(2)-induced apoptosis in PC12 cells. The main mechanism
      for these apoptosis appeared to be mitochondria-mediated pathway accompanied with
      loss of the mitochondrial transmembrane potential (Delta Psi m) followed by
      cytochrome c release from the mitochondria into the cytosol, resulting in the
      activation of caspase-9 and caspase-3. Also, upregulation of pro-apoptotic
      protein Bax, and downregulation of anti-apoptotic protein Bcl-2 by presence of
      CoCl(2) appeared significantly and it might result in activating mitochondria
      mediated apoptosis. We showed that expression of Fas and Fas ligand was
      upregulated and caspase-8 was significantly activated in CoCl(2)-induced
      apoptotic cells. In addition, ZB4, an antagonistic Fas-antibody, inhibited the
      activation of caspase-8 by CoCl(2), indicating that Fas receptor was involved in
      this pathway. These results demonstrate that CoCl(2) induce apoptosis in PC12
      cells via different dual apoptosis pathway through death receptor as well as
      mitochondria.

PMID- 15519735
TI  - Behavioral effects of metyrapone on Pavlovian extinction.
AB  - This is the first study of the action of metyrapone on Pavlovian extinction.
      Pavlovian acquisition memory can be impaired when 50 mg/kg metyrapone, a
      corticosterone synthesis inhibitor, is injected 90 min before training. It was
      hypothesized that the same treatment given before extinction may also impair
      Pavlovian extinction memory, and thereby facilitate recovery of the extinguished
      behavior. This study examined the behavioral effects of 50 mg/kg metyrapone on
      the extinction of conditioned freezing following Pavlovian conditioning of tone
      (CS) and footshock (US). On days 1-2, mice were habituated to the training
      context. On days 4-5, mice received 4 tone-shock pairings per day. On day 6,
      metyrapone or saline was injected s.c. 90 min before an extinction session with
      60 tone presentations. Probe sessions with 4 tones were conducted in the
      extinction context on day 7 and in the acquisition context on day 9. Metyrapone
      treatment did not affect performance during extinction or pre-CS freezing
      behavior. But metyrapone-treated animals showed greater conditioned freezing when
      tested with the tone the day after extinction in the extinction context
      (spontaneous recovery) and 3 days after extinction in the acquisition context
      (renewal effect). It was concluded that 50 mg/kg metyrapone did not affect
      extinction performance, but it effectively facilitated the subsequent recovery of
      the extinguished behavior. This effect may be explained by an impairment of the
      consolidation of the Pavlovian extinction memory. This interpretation is
      consistent with previous studies showing that metyrapone may interfere with
      memory consolidation for a variety of learned responses.

PMID- 15519736
TI  - Optical detection of convergent projections in the embryonic chick NTS.
AB  - Multiple-site optical recording of neural activity was performed in the nucleus
      of the tractus solitarius (NTS) of the chick embryo with stimulation of the
      glossopharyngeal nerve (N. IX) and vagus nerve (N. X). We measured the amplitudes
      of the optical signals related to glutamate-mediated excitatory postsynaptic
      responses, and calculated the ratio of the signal evoked by simultaneous N. IX/N.
      X stimulation to the signal obtained after mathematical summation of the
      individual N. IX and N. X responses. The ratio was significantly lower than 100%
      in the rostral region of the NTS, in which postsynaptic responses were elicited
      by both N. IX and N. X stimulations. This result means that there is a
      convergence of visceral inputs via the N. IX and N. X in the embryonic chick NTS.
      The existence of the convergence suggests that the NTS performs complex
      integration of information from multiple sensory inputs from the early stages of
      embryogenesis.

PMID- 15519737
TI  - Erythropoietin is neuroprotective in models of HIV sensory neuropathy.
AB  - HIV-associated sensory neuropathy (HIV-SN) is the most common neurological
      complication of HIV infection. Presently, there are no effective therapies for
      this painful neuropathy. The pathology of HIV-SN is characterized by 'dying back'
      sensory axonal degeneration and a more modest loss of dorsal root ganglion (DRG)
      sensory neurons. It has been hypothesized that HIV-SN results from neurotoxicity
      by secreted viral proteins, such as the HIV envelope glycoprotein gp120.
      Furthermore, neurotoxicity by dideoxynucleoside (DDX) agents, results in the
      observed higher incidence of HIV-SN in HIV-infected patients taking these
      antiretroviral drugs. In this study we show that administration of picomolar
      amounts of the hormone erythropoietin (EPO) prevents sensory axonal degeneration
      and in vitro DRG neuronal death by both gp120 and ddC (a neurotoxic DDX drug).
      Our results suggest that EPO may be useful in the treatment of HIV-SN.

PMID- 15519738
TI  - Zinc-histidine complex protects cultured cortical neurons against oxidative
      stress-induced damage.
AB  - The levels of zinc in the brain are directly affected by dietary zinc and
      deficiency has been associated with alcohol withdrawal seizures, excitotoxicity,
      impaired learning and memory and an accelerated rate of dysfunction in aged
      brain. Although zinc is essential for a healthy nervous system, high
      concentrations of zinc are neurotoxic, thus it is important to identify the most
      effective forms of zinc for treatment of conditions of the central nervous
      system. Accumulating evidence suggests that zinc-histidine complex (Zn(His)(2))
      has greater biological potency and enhanced bioavailability compared with other
      zinc salts and also has antioxidant potential. Therefore, in this study we
      investigated the ability of zinc-histidine to protect cultured cortical neurons
      against hydrogen peroxide-induced damage. Pre-treating neurons for 18 h with
      subtoxic concentrations of zinc-histidine (5-25 microM) improved neuronal
      viability and strongly inhibited hydrogen peroxide-induced (75 microM, 30 min)
      cell damage as assessed by MTT turnover and morphological analysis 24h later. Low
      concentrations of zinc-histidine were more neuroprotective than zinc chloride.
      There was evidence of an anti-apoptotic mechanism of action as zinc-histidine
      inhibited hydrogen peroxide-induced caspase-3 activation and c-jun-N-terminal
      kinase phosphorylation. In summary, zinc supplementation with zinc-histidine
      protects cultured neurons against oxidative insults and inhibits apoptosis which
      suggests that zinc-histidine may be beneficial in the treatment of diseases of
      the CNS associated with zinc deficiency.

PMID- 15519739
TI  - Effects of stimulus location on automatic detection of changes in motion
      direction in the human brain.
AB  - We extended the results of a previous report by further exploring the underlying
      mechanisms of an electrophysiological index of attention-free memory-based
      detection mechanism to motion-direction changes in the human visual system. By
      means of presenting bilateral, right- and left-hemifield stimulation in separate
      conditions, we tried to assess whether the location of the stimuli within the
      peripheral visual field affected the processing of motion-direction deviations,
      and to identify brain regions involved in the detection of unattended infrequent
      changes of motion direction using low-resolution brain electromagnetic tomography
      (LORETA). Results indicated that the ERP component related to visual change was
      not affected by stimulus location, and that bilateral temporal and medial regions
      were activated during this deviance-related response regardless of the hemifield
      stimulated. The bilateral activation foci observed in this study suggest that
      brain generators of this deviance-related component could be located at the
      vicinity of motion processing areas.

PMID- 15519740
TI  - Neuronal electrical high frequency stimulation modulates presynaptic GABAergic
      physiology.
AB  - Electrical high frequency deep brain stimulation (DBS) of the globus pallidus
      internus (GPi) or the subthalamic nucleus (STN) has dramatic beneficial motor
      effects in advanced Parkinson's disease (PD). However, the mechanisms underlying
      these clinical results remain unclear. It is proposed that the gamma-aminobutyric
      acid (GABA) system is involved in the effectiveness of DBS. To prove this
      hypothesis, rat striatal slices were stimulated electrically (130 Hz) in vitro;
      GABA and glutamate (GLU) outflow from striatal slices of normal or kainic acid
      lesioned rats were measured after o-phthaldialdehyde sulphite derivatization
      using HPLC with electrochemical detection. Our results could demonstrate that
      high frequency stimulation (HFS) did not modulate basal GABA outflow in the
      perfusate. In the presence of submaximal concentrations of the voltage-gated
      sodium channel opener veratridine, HFS significantly enhanced GABA outflow. When
      the GABA transporter inhibitor, nipecotic acid, was added to the incubation
      medium, the HFS effects decreased to nearly control values. Destruction of
      striatal GABAergic neurons by kainic acid completely reversed the effects of HFS
      on GABA outflow. In the present study no effect of HFS on glutamate outflow was
      observed under any condition. These results suggest that HFS has a specific
      effect on GABAergic neuronal terminals resulting in an enhancement of
      extracellular GABA in the caudate nucleus. This effect is probably due to an
      inhibitory effect of HFS on the GABA uptake system rather than to stimulation of
      vesicular GABA release from GABAergic neurons, which are both associated with the
      presynaptic GABAergic physiology.

PMID- 15519741
TI  - Lack of cross-tolerance to the antinociceptive effects of systemic and topical
      cannabinoids in morphine-tolerant mice.
AB  - Opioids and cannabinoids produce antinociception through activity at spinal,
      supraspinal and peripheral sites. Tolerance to the antinociceptive effects of
      both the opioids and the cannabinoids develop when these agents are administered
      chronically. Although mutual potentiation of antinociceptive effects have been
      reported between opioids and cannabinoids, the development of antinociceptive
      cross-tolerance between these systems has not been demonstrated consistently. In
      the present investigation, we explored the possibility of antinociceptive cross
      tolerance between systemic or topical morphine and systemic or topical
      cannabinoids in mice. Mice were made tolerant to morphine either by the
      subcutaneous (s.c.) implantation of a morphine pellet or repeated topical
      administration and then challenged with the mixed CB(1) and CB(2) receptor
      agonist WIN 55, 212-2 given s.c. or topically. Antinociception was indicated by
      increased tail-flick latencies to noxious radiant heat. Implantation with
      morphine pellets did not attenuate the antinociceptive potency of systemic or
      topical WIN 55,212-2. Moreover, twice-daily topical administration of morphine
      did not attenuate the antinociceptive potency of WIN 55,212-2 applied topically.
      These observations suggest that opioids and cannabinoids produce antinociception
      through mechanisms that are independent of each other at either the systemic or
      peripheral levels.

PMID- 15519742
TI  - Ethanol increases nuclear factor-kappa B activity in human astroglial cells.
AB  - Alcohol abuse adversely affects essentially all the organs of the body, either
      directly or indirectly. Ethanol may contribute to brain damage via inflammation.
      Ethanol may also alter CNS immunocompetence and further the progression of
      certain CNS infections. Nuclear factor (NF)-kappa B helps regulate inflammatory
      gene expression in glia. It is possible that ethanol effects on CNS pathology are
      partly a consequence of ethanol modulation of NF-kappa B-associated pathways in
      glia. We have assessed the effects of 0.5-6 h ethanol exposure on cytokine (5
      ng/ml interleukin-1 beta + 100 ng/ml interferon gamma + 30 ng/ml tumor necrosis
      factor-alpha)-induced NF-kappa B activation in human A172 astroglial cells.
      Immunoblot analysis indicated that NF-kappa B p65 nuclear translocation occurred
      within 0.5 h after cytokine stimulation. Stimulation in the presence of ethanol
      resulted in increased nuclear p65 levels at 3 h, with 200 mM causing a greater
      increase than 50 mM ethanol. Gel shift assay data suggested that cytokine-induced
      NF-kappa B binding activity was greatest in cells exposed to 50 mM ethanol,
      followed by 200 and 0 mM ethanol exposed cells, respectively. Thus, in cytokine
      stimulated cells, 200 mM ethanol resulted in greater nuclear p65 levels, yet, 50
      mM ethanol exposure resulted in more pronounced DNA binding by NF-kappa B. These
      findings demonstrate that acute ethanol enhances p65 activity in human astroglia
      and further support the hypothesis that ethanol-mediated brain pathology involves
      modulation of NF-kappa B pathways. A better understanding of the mechanistic
      events involved in ethanol-induced CNS pathology should provide for therapeutic
      strategies to combat detrimental effects of alcohol on the CNS.

PMID- 15519743
TI  - Corticotropin-releasing hormone potentiates neural injury induced by oxygen
      glucose deprivation: a possible involvement of microglia.
AB  - While corticotropin-releasing hormone (CRH) has been implicated in a variety of
      brain disorders such as ischemic injury, the molecular mechanism by which CRH
      elicits its activities is largely unclear. In the present study, we have
      determined the effect of CRH on oxygen-glucose deprivation (OGD) induced
      apoptosis in fetal hippocampal neurons. CRH alone at concentrations of 10-200 nM
      had no effect on neuronal apoptosis. However, when neurons were co-cultured with
      microglia, CRH alone at concentrations greater than 100 nM induced neuronal
      apoptosis and CRH potentiated significant neuronal apoptosis following exposure
      to OGD. The effect of CRH on neuronal apoptosis was inhibited in the presence of
      the CRH antagonist astressin. Real-time RT-PCR revealed an increase in mRNA
      levels of Fas ligand (Fas-L), a membrane protein related to the TNF family, in
      cultured microglia following OGD exposure. In the presence of CRH, OGD-induced
      Fas-L expression was significantly increased. The effect of CRH on Fas-L
      expression was inhibited by specific inhibitors of the extracellular signal
      regulated protein kinase (PD98059) and p38 mitogen-activated protein kinase
      (SB203580). These results suggest that CRH potentiates neuronal apoptosis induced
      by OGD in the presence of microglia and that this effect may be mediated through
      the induction of proinflammatory mediators in microglia.

PMID- 15519744
TI  - Rapid vestibular compensation in guinea pig even with prolonged anesthesia.
AB  - The results of previous studies have suggested that prolonged anesthesia
      following unilateral labyrinthectomy (UL) results in a retardation of vestibular
      compensation, the process of behavioral recovery that occurs following the
      lesion. In this study we investigated the effects of short-term (25 min) and long
      term (4 h) anesthesia with isoflurane on the time course of vestibular
      compensation following UL in guinea pig. Although there were significant
      differences in the frequency of spontaneous nystagmus (SN) (p < 0.05) and its
      rate of compensation (p < 0.05) between the 25 min and 4h isoflurane groups,
      these differences appeared to be due largely to the 5, 9 and 13 h time points.
      There was also a significant difference in the rate of yaw head tilt (YHT)
      compensation, largely due to the 5 h time point. When exponential regression
      analysis was performed to evaluate the overall pattern of compensation, there was
      no significant difference in the time required to reach 100% SN or YHT
      compensation between the 25 min and 4 h isoflurane groups. Furthermore, there
      were no significant differences in roll head tilt (RHT) compensation between the
      two groups. These results suggest that the time course of vestibular compensation
      is largely independent of the duration of the anesthesia used for UL surgery.

PMID- 15519745
TI  - Analysis of association between butyrylcholinesterase K variant and
      apolipoprotein E genotypes in Alzheimer's disease.
AB  - Recent studies indicate that there is a synergic association between
      butyrylcholinesterase-K variant (BChE-K) and apolipoproteinE-epsilon 4 (ApoE
      epsilon 4) to promote risk for Alzheimer's disease (AD). Most subsequently
      replicative studies have been unable to confirm these finding. We attempted to
      replicate this finding in 105 AD cases and age and sex matched 129 controls from
      Tehran population, Iran. The BChE genotype of patients were found to be
      significantly different from controls (chi(2) = 12.2, d.f. = 2, p = 0.002). The
      frequency of BChE-K allele was also found to differ significantly in cases
      compared to controls [24% versus 12% (chi(2) = 20.6, d.f. = 2, p < 0.001)]
      leading to an increased risk of AD in subjects with this allele (OR = 2.5, 95% CI
      = 1.64-3.8, p = 0.001). This risk was found to increase from (OR = 2.37, 95% CI =
      1.3-4.2, p = 0.006) in subjects less than 75 years old to (OR = 3.16, 95% CI =
      1.41-7.1, p = 0.001) in subjects 75 years and older. But, the ApoE-epsilon 4
      allele association risk was found to decrease from (OR = 9.5, 95% CI = 3.74-24.1,
      p = 0.001) in subjects <75 years to (OR = 1.36, 95% CI = 0.49-4.1, p = 0.58) in
      those subjects 75 years and older. Furthermore, we found a very strong synergic
      association between BChE-K and ApoE-epsilon 4 OR = 19.1 (95% CI = 428-85.45, p <
      0.001). In spite of this, synergism decreased from OR = 36.2 (95% CI = 4.4-296, p
      = 0.001) in subjects <75 year olds to OR = 6.2 (95% CI = 0.9-72.4, p = 0.06) in
      subjects > or =75 years. We have found that BChE-K and ApoE-epsilon 4 alleles act
      synergistically to increase the risk of the late-onset AD, particularly in age
      group <75 years in Tehran, Iran.

PMID- 15519746
TI  - Facilitatory effects of WAY-100635, a 5-HT1A receptor antagonist, on lordosis in
      female rats.
AB  - Effects of the serotonin (5-HT) receptor 1A antagonist, WAY-100635, on lordosis
      in female rats were examined. Ovariectomized rats were implanted with a silicon
      tube containing estradiol and behavioral tests were performed. Next, 5, 10 or 20
      mg/kg bw WAY-100635 or saline was injected subcutaneously in female rats with a
      lordosis quotient (LQ) from 10 to 30 and the behavioral test was performed again.
      As a result, the mean LQs in 10 or 20 mg WAY-100635-treated groups were higher
      than in the saline-treated group (P < 0.01 and P < 0.05, 10 or 20 mg groups
      versus saline, respectively). In the experiment on the time-course of change in
      LQ after injection with 10 mg WAY-100635, the mean LQ was increased (P < 0.01,
      versus saline) 15 min after the injection and high levels persisted for 1 h. This
      finding shows that WAY-100635 has the potency to enhance lordosis behavior
      acutely in female rats with a low estrous state. In order to investigate
      relationships between the 5-HT(1A) receptor and the GABA(B) receptor in
      regulating lordosis, 10 mg baclofen, a GABA(B) receptor agonist, was injected and
      this was followed 1 h later by the injection of 10 mg/kg WAY-100635. Mean LQ
      decreased after the injection of baclofen (P < 0.0001, versus placebo-treated
      control), but the decrease in LQs was not reversed by injection with WAY-100635.

PMID- 15519747
TI  - Dendritic localization of the RNA-binding protein HuD in hippocampal neurons:
      association with polysomes and upregulation during contextual learning.
AB  - The RNA-binding protein HuD binds to and stabilizes a number of neuronal-specific
      mRNAs. Recent work from our laboratory indicated that HuD expression is increased
      in neurons during peripheral nerve regeneration. To gain further insight into the
      function of this protein in CNS neurons we examined the levels of expression and
      localization of HuD in hippocampal neurons under normal conditions and in animals
      subjected to a learning paradigm, contextual fear conditioning (CFC). In the
      adult hippocampal formation, HuD immunoreactivity was highest in CA3 pyramidal
      neurons and interneurons in the hilus, moderate in the CA1 region and not
      detectable in dentate granule cells. Using confocal microscopy we found that HuD
      immunoreactivity was associated with large cytoplasmic granules in the neuronal
      cell body and smaller granules in dendrites. Both types of granules were also
      stained with the ribosomal marker Y10B, suggesting that they also contain
      ribosomes. Consistent with this idea, subcellular fractionation and
      immunoprecipitation analyses indicated that HuD is present in both the polysomal
      (P130) and cytosolic (S130) fraction. In addition to the basal pattern of HuD
      expression, we examined changes in the levels of this protein 24 h after rats
      were subjected to a single trial CFC paradigm. HuD protein expression was found
      to increase in the hilus and CA3 regions of the hippocampus but not in CA1. Our
      findings suggest that HuD plays a role in synaptic plasticity mechanisms
      stabilizing mRNAs associated with ribosomes both in the soma and dendrites of
      hippocampal neurons.

PMID- 15519748
TI  - Could mitochondrial haplogroups play a role in sporadic amyotrophic lateral
      sclerosis?
AB  - Mitochondrial impairment has been implicated in the pathogenesis of the
      amyotrophic lateral sclerosis (ALS). Furthermore, mitochondrial-specific
      polymorphisms were previously related to other neurodegenerative diseases, such
      as Parkinson, Friedreich and Alzheimer disease. To investigate if specific
      genetic polymorphisms within the mitochondrial genome (mtDNA) could act as
      susceptibility factors and contribute to the clinical expression of sporadic ALS
      (sALS), we have genotyped predefined European mtDNA haplogroups in 222 Italian
      patients with sALS and 151 matched controls. Individuals classified as haplogroup
      I demonstrated a significant decrease in risk of ALS versus individuals carrying
      the most common haplogroup, H (odds ratio 0.08, 95% confidence interval 0.04-0.4,
      p < 0.01). Further stratification of the dataset by sex, age and site of onset of
      disease and survival failed to reach significance for association. Our study
      provides evidence of the contribution of mitochondrial variation to the risk of
      ALS development in Caucasians. Further it may help elucidate the mechanism of the
      mitochondrial dysfunction detectable in ALS, and may be of relevance in
      development of strategies for the treatment of this disease.

PMID- 15519749
TI  - Plasminogen activities and concentrations in patients with sporadic Creutzfeldt
      Jakob disease.
AB  - Human plasminogen has been shown to interact with the abnormal disease-specific
      prion protein. Till now, no data are available for patients with Creutzfeldt
      Jakob disease (CJD). Therefore, we compared plasminogen concentrations and
      plasminogen activities in patients with sporadic CJD and controls with other
      dementia, which were collected in the framework of the German CJD Surveillance
      study. Patients with CJD had significantly higher plasminogen concentrations than
      patients with other forms of dementia and plasminogen specific activities were
      lower in CJD patients. The reasons for these abnormalities are not clear at the
      moment. The results may reflect a disease-specific prion protein and plasminogen
      interaction in patients with CJD. Other possible explanations are plasminogen
      polymorphisms and genotypes with distinct plasminogen activity levels in CJD than
      in controls, which should be a subject for further studies.

PMID- 15519750
TI  - The effect of WIN 55,212-2, a cannabinoid agonist, on tactile allodynia in
      diabetic rats.
AB  - The antinociceptive action of cannabinoids in acute and inflammatory pain states
      have been well-documented. There is also accumulating evidence suggesting that
      cannabinoids are effective analgesics in chronic pain conditions. WIN 55,212-2, a
      mixed CB1 and CB2 cannabinoid receptor agonist, has been shown to be effective
      against hyperalgesia and allodynia in painful peripheral mononeuropathy.
      Recently, in addition to their spinal and supraspinal antinociceptive action,
      cannabinoids have also reported to exert local analgesic effects. The aim of this
      study is to observe the effect of a high affinity cannabinoid, WIN 55,212-2, on
      tactile allodynia and thermal hyperalgesia in diabetic rats. Diabetes was
      produced with the injection of a single dose of streptozocin (50 mg/kg, i.p.) and
      this procedure resulted in neuropathic pain behaviors in the hindlimbs.
      Mechanical allodynia was detected by application of von Frey filaments to the
      plantar surface of the foot, and thermal hyperalgesia was studied using the
      Hargreaves' method; however, thermal hyperalgesia did not develop in diabetic
      rats. With its higher doses, both systemic (3 and 10 mg/kg, i.p.) and peripheral
      (30 microg, i.p.l.) injections of WIN 55,212-2 reduced mechanical allodynia.
      These results suggest that WIN 55,212-2 has an antiallodynic effect in
      streptozocin-induced diabetic rats and may be a promising approach in the
      treatment of diabetic neuropathy.

PMID- 15519751
TI  - A anticonvulsive fraction from Scaptocosa raptoria (Araneae: Lycosidae) spider
      venom.
AB  - Several spider neurotoxins are known to show highly selective effects on nervous
      tissues. Intracerebral injection into rats of spider venom from Scaptocosa
      raptoria, prevents seizures induced by convulsant agents. Injection of phenytoin
      (390 pmol/200 nl), muscimol (90 pmol/200 nl), baclofen (500 pmol/200 nl) into the
      substantia nigra (SN) pars reticulata, protected rats from convulsions evoked by
      unilateral focal injection of bicuculline into the area tempestas by 50, 80, and
      100%, respectively. Denatured S. raptoria crude venom (4.6 microg, 2.3 microg,
      and 920 ng/200 nl), when administered into the SN, prevented seizures elicited by
      bicuculline in the area tempestas by 100, 100, and 87.5%, respectively. The
      injection into the SN of 160 ng/200 nl of fraction SrTx1 isolated from S.
      raptoria venom, reduced the magnitude of seizures. This fraction was
      rechromatographed affording fractions SrTx1.1, SrTx1.2 and SrTx1.3, and they were
      administered into the SN at doses of 100, 200, and 400 ng/200 nl respectively.
      Fraction SrTx1.3 protected 50, 85.7, and 100% of the animals against the seizures
      elicited by bicuculline injected into the area tempestas. This suggests that S.
      raptoria venom as well as its SrTx1.3 fraction, might be potential sources of new
      anticonvulsant drugs.

PMID- 15519752
TI  - Labeling of the scrapie-associated prion protein in vitro and in vivo.
AB  - Prion diseases are a group of infectious neurodegenerative diseases that affect
      both animals and humans. A characteristic of prion diseases is the aggregation
      and accumulation of a disease-associated isoform of the prion protein in the
      brains of infected individuals. The amyloid imaging probe (trans,trans)-1-bromo
      2,5-bis-(3-hydroxycarbonyl-4-hydroxy)styrylbenzene (BSB) has shown potential in
      the diagnosis of other amyloid disorders and we hypothesized that this compound
      would be effective in labeling prion protein plaques in vitro and in vivo. To
      test this, we compared BSB fluorescence to prion protein immunostaining on
      infected and uninfected brain tissue sections from scrapie-infected hamsters. We
      found that both methods labeled the same plaques in infected tissues while not
      substantially staining uninfected tissues. To test the potential of BSB as an in
      vivo label for prion aggregates, we perfused scrapie-infected animals with BSB
      and observed BSB labeled plaques co-stained with an anti-prion protein antibody.
      These results suggest that BSB may have use as a diagnostic tool for prion
      diseases. We were unable to detect BSB staining in preclinical scrapie-infected
      hamsters suggesting that the diagnostic potential of BSB could be limited in
      cases of prion disease that do not have plaques either due to a preclinical lack
      of pathology or disease agents like sporadic Creutzfeldt-Jakob disease (CJD),
      which generally lack prion plaques. However, BSB may be a useful for prion
      diseases where plaques are present, such as clinical variant CJD.

PMID- 15519753
TI  - Natural rhythm: evidence for occult 40 Hz gamma oscillation in resting motor
      cortex.
AB  - Fast gamma oscillations, often at 40 Hz, have been demonstrated throughout the
      brain including the thalamus, auditory, visual and motor cortices. The function
      of gamma rhythms is elusive, but several authors have hypothesized that they
      contribute to the "binding" of diverse information into a single coherent
      percept, and to the synchronization of movement. In skeletal muscle a "Piper
      rhythm" around 40 Hz is commonly observed during maximal voluntary contraction,
      and has been shown to correlate with activity of similar frequency in a limited
      area of contralateral motor cortex. Gamma rhythms are detected primarily during
      complex cortical activity, and are seldom recorded at rest or coherently over
      wide areas. Here we use bihemispheric transcranial magnetic stimulation (TMS) to
      study time-dependent correlations between evoked motor potentials from non
      homologous muscles in opposite limbs of normal volunteers. The results suggest
      the presence of an occult, synchronous 40 Hz rhythm across broad areas of resting
      motor cortex in both hemispheres.

PMID- 15519754
TI  - The effect of rTMS over the cerebellum in normal human volunteers on peg-board
      movement performance.
AB  - Low frequency rTMS over the paramedian part of the right cerebellum was used to
      test the effects of TMS-induced disruption of the cerebellum on performance of
      the 10-hole pegboard task. A test group (n = 14) showed significantly increased
      movement times lasting about 3 min after the 5-min 1 Hz rTMS train, compared to a
      control group who received no rTMS (n = 14), tested in a parallel group design.
      The increase was greatest for the hand ipsilateral to the stimulation, but the
      difference between the two hands was not statistically significant. These results
      suggest that the rTMS affects cerebellar excitability and cause a short-lasting
      bilateral change in sensory-motor performance.

PMID- 15519755
TI  - Exposure to hypomagnetic field space for multiple generations causes amnesia in
      Drosophila melanogaster.
AB  - This is the introduction of Drosophila into the study of learning and memory
      affected by removal of the geomagnetic field (GMF) for successive generations.
      Using the operant visual learning/memory paradigm at a flight simulator, the
      present study revealed that wild-type flies raised in a hypomagnetic field
      environment continuously for 10 successive generations were gradually impaired in
      visual conditioning learning and memory formation and finally the 10th generation
      flies became morphs of nonlearners and completely amnesiac. The control
      experiments show that the impairment could not be ascribed to any apparent
      sensorimotor problems in Drosophila. The reverse shift from hypomagnetic field
      (HMF) to natural GMF restored the GMF-free induced amnesia fully after six
      consecutive generations. Thus, our findings demonstrate conclusively that some
      serious, but reversible learning and memory impairment may occur for living
      organisms in a prolonged separation from GMF over many consecutive generations.
      And Drosophila has the potential to develop into a new model organism for the
      study of the neurobiology of magnetism for multiple generations.

PMID- 15519756
TI  - S100 protein-like immunoreactivity in the crypt olfactory neurons of the adult
      zebrafish.
AB  - The olfactory epithelium of some teleosts, including zebrafish, contains three
      types of olfactory sensory neurons. Because zebrafish has become an ideal model
      for the study of neurogenesis in the olfactory system, it is of capital
      importance the identification of specific markers for different neuronal
      populations. In this study we used immunohistochemistry to analyze the
      distribution of S100 protein-like in the adult zebrafish olfactory epithelium.
      Surprisingly, specific S100 protein-like immunostaining was detected exclusively
      in crypt neurons, whereas ciliated and microvillous neurons were not reactive,
      and the supporting glial cells as well. The pattern of immunostaining was
      exclusively cytoplasmic without apparent polarity within the soma, and the
      intensity of immunostaining was not related with the maturative stage of the
      neurons. The role of S100 protein in crypt olfactory neurons is unknown, although
      it is probably associated with the capacity of these cells to respond to chemical
      stimuli. In any case, it represents an excellent marker to identify crypt
      olfactory neurons in zebrafish.

PMID- 15519757
TI  - Progressive changes in regulation of apolipoproteins E and J in glial cultures
      during postnatal development and aging.
AB  - Apolipoprotein (Apo) E and ApoJ are lipid- and cholesterol-carriers in the
      central nervous system and are implicated in age-related neurodegenerative
      diseases. The primary source of secreted ApoE and ApoJ (clusterin) in the brain
      is glia. Regulation of these apolipoproteins in mixed glial cultures from rat
      cerebral cortex differed most strongly between neonatal- and adult-derived glia.
      Basal secretion of ApoJ was two-fold greater in neonatal than adult glia.
      Responses to cytokines also differed by donor age. In adult glia, IL-6 increased
      ApoE secretion, but slightly decreased ApoJ. Both IL-1 beta and TNFalpha
      treatments increased ApoJ secretion from adult glia, with little effect on ApoE.
      In contrast to adult glia, neonatal ApoJ secretion did not respond to IL-1 beta,
      IL-6, or TNFalpha, and ApoE secretion from neonatal glia was slightly increased
      by IL-6. These differences may contribute to age-related neuroinflammatory
      processes, and are pertinent to the general use of neonatal-derived primary glia
      in models for neurodegenerative disease.

PMID- 15519758
TI  - The neuroprotective effect of melatonin against the induction of c-Jun
      phosphorylation by 6-hydroxydopamine on SK-N-SH cells.
AB  - Melatonin is synthesized mainly in pineal gland. It has been suggested that
      melatonin has proven antioxidant effects and protective effects against neuronal
      cell degeneration. There are several studies indicating that c-Jun-N-terminal
      kinase pathways might be involved in neuronal cell death. In this study, the
      effects of melatonin on 6-hydroxydopamine (6-OHDA)-treated cultured SK-N-SH cells
      were investigated. The results showed that 6-OHDA significantly decreased cell
      viability as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium
      bromide (MTT) assay, and melatonin was able to reverse the toxic effects of 6
      OHDA on cell viability. In addition, induction of c-Jun phosphorylation by 6-OHDA
      was diminished by melatonin. These results demonstrate some protective properties
      of melatonin against neuronal cell degeneration and its action on the inhibition
      of c-Jun-N terminal kinase signaling cascade.

PMID- 15519759
TI  - Rosuvastatin reduces caspase-3 activity and up-regulates alpha-secretase in human
      neuroblastoma SH-SY5Y cells exposed to A beta.
AB  - An increasing number of studies suggest that disturbances in cholesterol
      homeostasis may promote the formation and deposition of beta-amyloid (A beta) and
      the progression of Alzheimer's disease (AD). In this paper, we have analyzed the
      effect of the lipid-lowering compound rosuvastatin on apoptosis and caspase-3
      activity in human neuroblastoma SH-SY5Y cells. Exposure of SH-SY5Y cells to A
      beta(1-42) alone resulted in a significantly increased caspase-3 activity
      approximately by 35% (135+/-15%, p<0.05), and decreased alpha-secretase activity
      by 34% (67.4+/-2.7%, p<0.001) compared to the controls (100+/-18.1%).
      Rosuvastatin alone decreased caspase-3 activity by 15% (85.3+/-1.5%, p<0.0005)
      compared to the controls and by 50% to cells exposed to A beta alone (p<0.00005).
      Cells exposed to rosuvastatin alone had a higher alpha-secretase activity
      compared to cells exposed to A beta (76.4+/-23.8%, n.s.) but a slightly lower
      activity compared to the controls (n.s.). Pre-treatment of SY-SY5Y cells with
      rosuvastatin prior to incubation with A beta(1-42) resulted in decreased caspase
      3 activity by approximately 15% compared to the controls and by approximately 48%
      (86.8+/-16.9%, p<0.05) compared to cells treated with A beta(1-42) alone. Also,
      alpha-secretase activity was increased by approximately 50% compared to the
      controls and by 84% (151.3+/-10.1%, p<0.05), compared to cells treated with A
      beta(1-42) alone. Mevalonate abrogated the effect of rosuvastatin in vitro. To
      our knowledge, this is the first study demonstrating that the hydrophilic
      compound rosuvastatin decreases caspase-3 activity and increases alpha-secretase
      activity in human neuroblastoma SH-SY5Y cells exposed to A beta in vitro. These
      effects are essential for modulation of the amyloidogenic pathway and mediators
      of apoptosis in AD.

PMID- 15519760
TI  - Immunolocalization of 14-3-3 isoforms in brains with Pick body disease.
AB  - Immunolocalization of 14-3-3 protein isoforms in relation to Pick bodies in Pick
      body disease (PBD) brains was investigated. Weakly granular immunoreactivity of
      14-3-3 proteins was found in neurons in control subjects and in Pick body disease
      brains. In addition to this granular immunoreactivity, many Pick bodies were
      immunopositive for 14-3-3 proteins as confirmed with double-immunofluorescence
      with an anti-PHF tau (AT8) and anti-14-3-3 that recognizes all its isoforms
      (common). When probed with isoform-specific antibodies, Pick bodies were positive
      for beta, gamma, epsilon, eta, tau, and zeta isoform and exhibited immunostaining
      pattern similar to that observed with the anti-14-3-3 proteins (common). In
      addition, immunoreactivity of sigma isoform, so far considered to be exclusively
      extraneuronal, was unexpectedly found in Pick bodies, normal hippocampal neurons
      and brain homogenate from age-matched controls. Although localization of 14-3-3
      proteins in Pick bodies suggests their involvement in Pick body formation, their
      role may be variable dependent on the isoforms differently expressed in different
      area in the brain.

PMID- 15519761
TI  - Movement preparation in self-initiated versus externally triggered movements: an
      event-related fMRI-study.
AB  - In the present study, we used fMRI to investigate whether event-related
      preparatory processes of self-initiated and externally triggered movements
      differ. Twenty subjects were examined with 1000 T2*-weighted images in two
      consecutive sessions. During the first session subjects performed self-initiated
      abductions of the right index finger. For the second session subjects were
      instructed to perform the movements in response to visual cues. Number and timing
      of movements were matched between conditions. For statistical inference on
      multisubject level, random effects analyses were performed. Significantly
      enhanced activity during self-initiated compared to externally triggered
      movements was found within the left SMA, the left pre- and sensorimotor cortex,
      the right putamen, the left anterior cingulate gyrus, and the left inferior
      parietal lobe. The significantly increased activity during self-initiated in
      comparison to externally triggered movements might represent differential demands
      of the two conditions on the neuronal motor net during movement preparation,
      reflecting utilization of precise knowledge when to move in self-initiated
      movements. Our results emphasize a possible role of the primary motor cortex for
      movement preparation as observed in electrophysiological studies, but do not
      support a specific involvement of the dorsolateral prefrontal cortex as suggested
      by former block design studies.

PMID- 15519762
TI  - The advanced glycation end-product N epsilon-(carboxymethyl)lysine level is
      elevated in cerebrospinal fluid of patients with amyotrophic lateral sclerosis.
AB  - Oxidative stress is involved in the aetiopathogenesis of amyotrophic lateral
      sclerosis (ALS), a fatal degenerative disorder. To test whether oxidative stress
      in ALS is increased and confined to the central nervous system, we have measured
      the glycoxidation product N(epsilon)-(carboxymethyl)lysine (CML) in serum and
      cerebrospinal fluid (CSF) samples by means of a novel enzyme immunoassay.
      Significant increases of CSF/serum ratio of CML in ALS patients (n = 25) as
      compared to normal controls (n = 20, p = 0.001) and to Alzheimer disease patients
      (n = 9, p = 0.029) suggest intrathecal production of this glycoxidation product.
      Measurement of CML levels may provide a novel diagnostic tool and may supplement
      current monitoring strategies in interventional trials.

PMID- 15519764
TI  - The spinal muscarinic receptor subtypes contribute to the morphine-induced
      antinociceptive effects in thermal stimulation in mice.
AB  - The present study was undertaken to clarify how spinal muscarinic receptors can
      be involved in the antinociceptive effects induced by morphine in thermal
      stimulation. The morphine-induced antinociceptive effects (26.6 micromol/kg,
      s.c.) was inhibited by an intrathecal (i.t.) injection of the muscarinic
      antagonist (M) atropine and the M(1)/M(4) antagonist pirenzepine in a dose
      dependent manner. In contrast, the M(2) antagonist methoctramine and the M(3)
      antagonist 4-DAMP did not inhibit the morphine-induced antinociceptive effects.
      Injection (i.t.) of the putative M(1) agonist McN-A-343 resulted in dose
      dependent antinociceptive effects in thermal stimuli. In addition,
      antinociceptive effects induced by the i.t. injection of morphine were not
      inhibited by the M(1)/M(4) antagonist pirenzepine, although pirenzepine did
      inhibit the intracerebroventricular (i.c.v.) injection of morphine-induced
      antinociceptive effects. These results suggest that the morphine-induced
      antinociceptive effects in thermal stimuli are regulated by the M(1) or M(4)
      receptor in the spinal cord.

PMID- 15519763
TI  - Evaluation of a proposed mechanism of ligand-gated ion channel activation in the
      GABAA and glycine receptors.
AB  - Ligand-gated ion channels (LGICs) mediate rapid chemical neurotransmission in the
      mammalian brain. This gene superfamily includes the nicotinic acetylcholine
      (nAChR), GABA(A), 5-hydroxytryptamine type 3, and glycine receptors. Upon agonist
      binding these receptors undergo a rapid allosteric transition from the closed to
      open state. The molecular mechanism of coupling between agonist binding and
      channel gating remains poorly understood, in part due to the lack of a high
      resolution structure of the entire receptor. Miyazawa, Fujiyoshi, and Unwin
      published a 4A resolution structure of the nAChR, and proposed that a single
      residue--valine 44 in Loop 2 of the extracellular domain--functions as a critical
      determinant of a "pin-into-socket" mechanism for receptor activation in nAChR.
      Here we examined whether this proposed "pin-into-socket" mechanism also
      contributes to channel activation in the GABA(A) and glycine receptors. We
      mutated residues corresponding to nAChR valine 44 in the GABA(A) (alpha(1)
      histidine 56 and beta(2) valine 53) and glycine (alpha(1) threonine 54)
      receptors. The results obtained in this study do not support a simple "pin-into
      socket" mechanism of activation for the activation of GABA(A) and glycine
      receptors. This conclusion is consistent with other recent reports in which
      mutations of residues distributed throughout several loops of nAChR, GABA(A) and
      glycine receptors had large effects on gating behavior.

PMID- 15519765
TI  - Abnormal migration of human wild-type alpha-synuclein upon gel electrophoresis.
AB  - Alpha-synuclein aggregates have been linked to the pathogenesis of Parkinson's
      disease (PD), with Lewy bodies (LBs) and Lewy neurites (LNs) constituting the
      pathological hallmarks in the brains of patients with PD and dementia with LBs.
      LBs are formed by the conversion of soluble monomers of alpha-synuclein into
      insoluble aggregates. Here we report an abnormal electrophoretic mobility, at a
      higher molecular weight (MW) than the expected theoretical MW, of both
      recombinant histidine-tagged human alpha-synuclein, human alpha-synuclein
      expressed in SH-SY5Y human neuroblastoma cells or Ltk(-) fibroblasts, and rat
      brain alpha-synuclein, on SDS-PAGE polyacrylamide, but not on Nu-PAGE gradient
      peptide, gels, suggesting possible alpha-synuclein data misinterpretations
      associated with gel electrophoresis. These studies raise important considerations
      about the type of protein gel electrophoresis system suitable to study the
      alterations of alpha-synuclein associated with neurodegeneration, PD and other
      synucleinopathies.

PMID- 15519766
TI  - Light response of the neuronal firing activity in the suprachiasmatic nucleus of
      mice.
AB  - To investigate the neural mechanisms underlying the mammalian photic entrainment
      of circadian rhythms, the response of neuronal extracellular firing activity to
      retinal light stimulation was investigated in the suprachiasmatic nucleus (SCN)
      of anesthetized mice during nighttime and daytime. In nighttime, most recorded
      SCN cells (83%) increased their firing frequency in response to retinal
      illumination. Some SCN cells (11%) responded by decreasing their firing rate. In
      daytime, the retinal illumination increased the firing rate in only 26% of the
      SCN cells, and no response was observed in the remaining cells. The light
      intensity threshold for the activation of SCN cells at zeitgeber time (ZT) 16 was
      approximately 3 x 10(11) photons cm(-2)s(-1) and the maximum response was
      observed at approximately 1 x 10(14) photons cm(-2)s(-1). Therefore, photic
      response in the firing of mouse SCN cells may be phase-dependent and have a
      higher threshold, which corresponds to properties of the photic entrainment in
      locomotor activity of mice.

PMID- 15519767
TI  - Neural progenitor cells do not differentiate prematurely in presenilin-1 null
      mutant mice.
AB  - Mice with a null mutation of the presenilin-1 (PS1-/-) gene die during late
      intrauterine life or shortly after birth and exhibit defects in cortical
      development. A previous report suggested that neurons differentiate prematurely
      in PS1-/- brain [M. Handler, X. Yang, J. Shen, Presenilin-1 regulates neuronal
      differentiation during neurogenesis, Development 127 (2000) 2593-2606]. Here we
      reexamined the issue of whether premature neuronal differentiation occurs in PS1
      /- brain using fresh cell suspensions from embryonic E11.5 and E13.5
      telencephalon where individual cell phenotypes can be easily determined with cell
      type specific markers. Immunostaining with seven neuronal specific markers (MAP2,
      beta-III tubulin, GABA, reelin, GluR2/3, calbindin, and calretinin) failed to
      reveal any evidence of premature neuronal differentiation in PS1-/-
      telencephalon. We also determined the fraction of cells expressing the neural
      progenitor marker nestin and found no evidence for premature depletion of neural
      progenitor cells in PS1-/- telencephalon. Moreover, based on MAP2 staining of
      tissue sections from E12.5 embryos the topography of newly generated neurons also
      appeared to be undisturbed in the telencephalon of PS1-/- embryos. These studies
      thus argue that premature neuronal differentiation is unlikely to be a core
      pathophysiological feature underlying the aberrant cortical development that
      occurs in PS1-/- brain.

PMID- 15519768
TI  - Fractionation and late rectal toxicity.

PMID- 15519769
TI  - Is prostate cancer like lung cancer?

PMID- 15519770
TI  - Prophylaxis versus treatment: is there a better way to manage radiotherapy
      induced nausea and vomiting?
AB  - Nausea and vomiting are two of the most distressing side effects of radiotherapy
      and cytotoxic drugs, which currently are often combined to treat moderately
      advanced and advanced solid tumors. Inadequate control of these symptoms may
      result in significant patient suffering and decrease in the patient's quality of
      life, which has been shown to decrease patients' compliance to treatment, with
      potential impact on disease outcome. It is, therefore, important that radiation
      oncologists recognize the need for adequate prophylactic treatment of radiation
      induced nausea and vomiting (RINV) to avoid the detrimental effects on patients'
      quality of life, and optimize chances for cure. The 5-hydroxytryptamine type 3 (5
      HT(3))-receptor antagonists have been proved to provide effective antiemetic
      therapy in patients undergoing highly emetogenic radiotherapy. Nevertheless,
      several large surveys have shown that optimal treatments are not always used.
      Hence, a risk exists that waiting for RINV symptoms rather than prescribing
      prophylactic antiemetic treatment may lead to increased patient suffering, poorer
      disease control, and less cost-effective therapy options. Prophylactic management
      with an effective 5-HT(3)-receptor antagonist should offer a better treatment
      option for patients at high to moderate risk of RINV. Adequate control of RINV
      should contribute to patient compliance to treatment, improved therapy outcomes,
      and decreased burdens on nursing and health care resources.

PMID- 15519771
TI  - American Society for Therapeutic Radiology and Oncology and American College of
      Radiology practice guideline for the performance of stereotactic body radiation
      therapy.

PMID- 15519772
TI  - Rectal bleeding after hypofractionated radiotherapy for prostate cancer:
      correlation between clinical and dosimetric parameters and the incidence of grade
      2 or worse rectal bleeding.
AB  - PURPOSE: To investigate the incidence and severity of rectal bleeding after high
      dose hypofractionated radiotherapy (RT) for prostate cancer, and to explore the
      factors affecting the incidence of Grade 2 or worse rectal bleeding. METHODS AND
      MATERIALS: The data of 52 patients who had been treated by external beam RT for
      localized prostate cancer between 1999 and 2002 were analyzed. All the patients
      had received hypofractionated external beam RT to a total dose of 69 Gy in 3-Gy
      fractions, three fractions weekly. The clinical and dosimetric factors affecting
      the incidence of Grade 2 or worse late rectal bleeding were analyzed by
      univariate and multivariate analyses. The effect of the percentage of the whole
      rectal volume receiving 30%, 50%, 80%, and 90% of the prescribed radiation dose
      (V(30), V(50), V(80), and V(90), respectively) on the incidence of rectal
      bleeding was evaluated. RESULTS: Of the 52 patients, 13 (25%) developed Grade 2
      or worse rectal bleeding. One patient who needed laser coagulation and blood
      transfusion for the treatment of rectal bleeding was classified as having Grade 3
      rectal bleeding. The median time to the development of Grade 2 or worse rectal
      bleeding was 11 months. The results of the univariate analysis revealed that the
      presence of a history of diabetes mellitus (p < 0.001), and V(30) >/= 60%, V(50)
      >/= 40% (p < 0.05), V(80) >/= 25%, and V(90) >/= 15% (p < 0.001) were
      statistically significant risk factors for the occurrence of Grade 2 or worse
      rectal bleeding. The results of the multivariate analysis revealed that a history
      of diabetes mellitus was the most statistically significant risk factor for the
      occurrence of rectal bleeding after hypofractionated RT for prostate cancer (p <
      0.05). CONCLUSION: A history of diabetes mellitus was the most statistically
      significant risk factor for the occurrence of Grade 2 or worse rectal bleeding
      after high-dose hypofractionated RT, although dosimetric factors were also
      closely associated with the risk of rectal bleeding.

PMID- 15519773
TI  - PSA failure and the risk of death in prostate cancer patients treated with
      radiotherapy.
AB  - PURPOSE: To determine the relationship between prostate-specific antigen (PSA)
      failure and cause-specific and overall survival in prostate cancer patients
      treated with radical radiotherapy. METHODS AND MATERIALS: Patients with and
      without PSA failure were compared with respect to overall survival and cause
      specific survival in a cohort of 1786 patients. The relationship between PSA
      failure and survival was further investigated among six subgroups defined by
      three tumor risk groups (high, intermediate, and low risk based on T stage,
      Gleason score, and presenting PSA) and two age groups (<75 years and >/=75
      years). RESULTS: The 5-year overall survival among patients who had PSA failure
      was 79.5% vs. 87.5% among patients who had not failed (p = 0.0003). The
      corresponding 5-year cause-specific survival was 84.4% vs. 99.0% (p <0.0001).
      When the six subgroups are considered separately, PSA failure was associated with
      a worse cause-specific survival in the groups with intermediate- and high-risk
      disease. PSA failure was only associated with a worse overall survival in one
      subgroup: patients younger than 75 with high-risk disease. Deaths from
      nonprostate causes made the survival curves of patients with and without PSA
      failure in the other subgroups almost identical. CONCLUSION: PSA failure in
      prostate cancer patients treated with radiotherapy was associated with a poorer
      overall survival, which is seen mainly in younger patients with high-risk
      disease.

PMID- 15519774
TI  - Use of MRI and spectroscopy in evaluation of external beam radiotherapy for
      prostate cancer.
AB  - PURPOSE: To characterize the metabolic response in the prostate, the time to
      resolution of disease, and the correlation between magnetic resonance imaging
      (MRI) with spectroscopy (MRSI) results, biopsy findings, and serum prostate
      specific antigen (PSA) level after external beam radiotherapy. METHODS AND
      MATERIALS: A total of 55 patients underwent MRSI before and/or at varying times
      after external beam radiotherapy. The percentage of the cancerous, healthy, and
      atrophic voxels was calculated, and the time to resolution of disease was
      determined and compared with the PSA nadir. RESULTS: Of the 55 patients, 70% had
      negative MRSI and 30% had positive MRSI findings. A strong correlation was found
      between negative MRSI and negative biopsy findings (n = 11) and between positive
      MRSI and positive biopsy findings (n = 7). A weak correlation was observed
      between the PSA level and the MRSI and biopsy findings. The mean time to disease
      resolution was 40.3 months and the mean time to PSA nadir was 50 months. With
      time, an increase in atrophy and a decline in cancerous metabolism was found.
      CONCLUSION: When used in conjunction with PSA measurement and biopsy, the results
      of this study suggest that MRSI contributes to a greater level of confidence in
      determining the outcome and may be a useful adjunct for assessing local control
      before PSA failure when striving to distinguish the benign "blip" from local
      recurrence.

PMID- 15519775
TI  - The GETUG 70 Gy vs. 80 Gy randomized trial for localized prostate cancer:
      feasibility and acute toxicity.
AB  - PURPOSE: To describe treatments and acute tolerance in a randomized trial
      comparing 70 Gy and 80 Gy to the prostate in patients with localized prostate
      cancer. METHODS AND MATERIALS: Between September 1999 and February 2002, 306
      patients were randomized to receive 70 Gy (153 patients) or 80 Gy (153 patients)
      in 17 institutions. Patients exhibited intermediate-prognosis tumors. If the risk
      of node involvement was greater than 10%, surgical staging was required. Previous
      prostatectomy was excluded, and androgen deprivation was not admitted. The
      treatment was delivered in two steps. PTV1-including seminal vesicles, prostate,
      and a 1-0.5-cm margin-received 46 Gy given with a 4-field conformal technique.
      PTV2, reduced to prostate with the same margins, irradiated with at least 5
      fields. Dose was prescribed according to ICRU recommendations in the 70 Gy group,
      but adapted at the 80 Gy level. RESULTS: All patients but one in the 80 Gy arm
      completed the treatment. In the 70 Gy arm, the mean dose to the PTV2 was 69.5 Gy.
      In the 80 Gy arm, the mean dose in the PTV2 was 78.5 Gy. Acute toxicity according
      to Radiation Therapy Oncology Group scale during treatment was reported in 306
      patients. There was no statistically significant difference between the two arms:
      12% had no toxicity, 80% complained of bladder toxicity, and 70% complained of
      rectal symptoms. Two months after the end of treatment, 43% of the 70 Gy level
      and 48% of the 80 Gy level complained of side effects, including 24% and 20% of
      sexual disorders. There was 6% and 2% of Grade 3 urinary and rectal toxicity.
      Five patients required a 10-29-day suspension of the treatment. Acute Grade 2 and
      3 side effects were related to PTV and CTV1 size, which was the only independent
      predictive factor in multivariate analysis. Toxicity was not related to the
      center, age, arm of treatment, or selected data from dose-volume histogram of
      organ at risk. CONCLUSION: Treatments were completed in respect to constraints.
      Acute toxicity was acceptable. Intensity of toxicity depended on target volumes.

PMID- 15519776
TI  - Longitudinal assessment of changes in sexual function and bother in patients
      treated with external beam radiotherapy or brachytherapy, with and without
      neoadjuvant androgen ablation: data from CaPSURE.
AB  - PURPOSE: To evaluate the effects of external beam radiotherapy (EBRT), with or
      without brachytherapy (BT) boost or brachytherapy monotherapy with and without
      short-term androgen ablation (<==6 months; STAD) on sexual function (SF) and
      sexual bother (SB) in men treated for localized prostate cancer. METHODS AND
      MATERIALS: A total of 992 men with newly diagnosed prostate cancer enrolled in
      the Cancer of the Prostate Strategic Urological Research Endeavor database were
      studied to assess treatment-related changes in SF and SB. Six treatment subgroups
      (EBRT - STAD, EBRT + STAD, BT - STAD, BT + STAD, EBRT + BT - STAD, EBRT + BT +
      STAD) were compared. RESULTS: The greatest reported changes in SF occurred during
      the first 2 posttreatment years. Patients receiving BT reported greater SF and
      the least change in SF overall; those receiving EBRT + BT reported the greatest
      decline in SF. SF scores associated with STAD were initially lower than in
      patients without STAD; however by 1 year no statistically significant difference
      in SF or SB was noted. CONCLUSION: Each treatment for prostate cancer can
      negatively affect SF and SB. Initial differences among treatment subgroups exist,
      but diminish with time. SF changes associated with EBRT +/- BT were statistically
      significant and those for BT were not. STAD appeared to confer only temporary and
      recoverable impairment of erectile function.

PMID- 15519777
TI  - Do differences in target volume definition in prostate cancer lead to clinically
      relevant differences in normal tissue toxicity?
AB  - PURPOSE: Many studies have described the quantitated differences between
      clinicians in target volume definition in prostate cancer. However, few studies
      have looked at the clinical effects of this. We aimed to assess the relevance and
      sequelae of such differences. METHODS AND MATERIALS: Five experienced radiation
      oncologists were given the clinical details of 5 patients with early-stage
      prostate cancer and asked to define the clinical target volume, consisting of the
      prostate and seminal vesicles (CTV1) and the prostate alone (CTV2), on specified
      planning CT scans of the pelvis. Planning target volumes (PTV1) were generated by
      automatic expansion of the CTV1 by a 1-cm margin. The PTV2 was defined as the
      CTV2. The rectum and bladder were defined by a single experienced clinician for
      each plan without knowledge of the involved clinician marking the CTVs. The
      Pinnacle planning system was used to generate the plans, using four-field
      conformal radiotherapy, to deliver 64 Gy in 32 fractions to the PTV1 followed by
      a boost of 10 Gy to the PTV2 (Medical Research Council RT01 trial protocol). Dose
      volume histograms were generated for the whole bladder and rectum for each plan
      and the volume receiving a specific percentage of the dose (e.g., V(90))
      calculated for 74 Gy, followed by estimates of normal tissue complication
      probabilities (NTCPs) for the bladder and rectum. RESULTS: Statistically
      significant differences were found in the CTV1 and CTV2 and, consequently, the
      PTV1 among the 5 clinicians (p < 0.0005). Most of the discrepancies occurred at
      the delineation of the prostatic apex and seminal vesicles, with the smallest
      variance noted at the rectum-prostate and bladder-prostate interfaces. No
      statistically significant differences were found among clinicians for the rectal
      V(90), V(85), V(80), V(70), or V(50) or for the bladder V(85), V(80), V(70), or
      V(50). A difference was noted among consultants for the bladder V(90) (p =
      0.015), although no correlation was found between the bladder V(90) and the size
      of the outlined volumes. No statistically significant differences were found
      between the estimates of bladder (p = 0.1) and rectal (p = 0.09) NTCPs.
      CONCLUSION: The statistically significant difference in outlined volumes of the
      CTV1, CTV2, and PTV1 among the 5 clinicians is in keeping with the findings of
      previous studies. However, the interclinician variability did not result in
      clinically relevant outcomes with respect to the irradiated volume of rectum and
      bladder or NTCP. This may have been because the outlined areas in which
      interclinician differences were smallest (the rectal-prostate and prostate
      bladder interfaces) are the areas that have the greatest effect on normal tissue
      toxicity. For the areas in which the interclinician correlation was lowest (the
      prostatic apex and distal seminal vesicles), the effects on normal tissue
      toxicity are smallest. The results of this study suggest that interclinician
      outlining differences in prostate cancer may have less clinical relevance than
      was previously thought.

PMID- 15519778
TI  - Both pretreatment prostate-specific antigen level and posttreatment biochemical
      failure are independent predictors of overall survival after radiotherapy for
      prostate cancer.
AB  - PURPOSE: To assess the impact of pretreatment prognostic factors plus subsequent
      biochemical failure on overall survival after radiotherapy for prostate cancer.
      METHODS AND MATERIALS: We analyzed the prostate-specific antigen (PSA) and
      survival records of 1571 men with clinically localized prostate cancer treated
      with external beam radiotherapy monotherapy at the former Queensland Radium
      Institute between 1990 and 1997. The pretreatment PSA level, biopsy Gleason
      score, clinical stage, patient age, and the development of biochemical failure
      were assessed in relationship to overall survival and cause-specific survival,
      using fixed, as well as time-dependent, statistics. RESULTS: The median follow-up
      was 88.1 months (95 months for those still alive). The actuarial overall
      survival, cause-specific survival, and biochemical failure-free survival rate at
      10 years was 61.1%, 80.9%, and 25.9% respectively. Cause-specific survival was
      independently influenced by the pretreatment PSA level, Gleason score, clinical
      stage, and the development of biochemical failure (relative risk, 19.1). Using
      the overall survival endpoint, multivariate analysis showed age, pretreatment PSA
      level, Gleason score, and biochemical failure (relative risk 1.27) to be
      statistically significant variables. CONCLUSION: In addition to previously
      identified factors, the pretreatment PSA level and occurrence of biochemical
      failure after radiotherapy for prostate cancer are associated with an increased
      overall mortality risk. Both pretreatment PSA level and posttreatment biochemical
      failure are independent predictors of overall survival after radiotherapy for
      prostate cancer.

PMID- 15519779
TI  - Effect of oral sucralfate on late rectal injury associated with radiotherapy for
      prostate cancer: A double-blind, randomized trial.
AB  - PURPOSE: To assess whether oral sucralfate is effective in preventing late rectal
      injury in prostate cancer patients treated with radiotherapy. METHODS AND
      MATERIALS: A double-blind, placebo-controlled, randomized trial was conducted
      across four institutions in Australia. Patients receiving definitive radiotherapy
      for prostate cancer were randomized to receive either 3 g of oral sucralfate
      suspension or placebo twice daily. Data on patients' symptoms were collected for
      2 years, and flexible sigmoidoscopy was scheduled at 12 months after treatment.
      RESULTS: A total of 338 patients were randomized, of whom 298 had adequate follow
      up data available for an analysis of late symptoms. Of the 298 patients, 143 were
      randomized to receive sucralfate and 155 placebo. The cumulative incidence of
      Radiation Therapy Oncology Group Grade 2 or worse late rectal toxicity at 2 years
      was 28% for placebo and 22% for the sucralfate arm (p = 0.23; 95% confidence
      interval for the difference -3% to 16%). Seventeen percent of patients in the
      sucralfate group had significant bleeding (Grade 2 or worse) compared with 23% in
      the placebo group (p = 0.18, 95% confidence interval -15% to 3%). No
      statistically significant difference was found between the two groups with
      respect to bowel frequency (p = 0.99), mucus discharge (p = 0.64), or fecal
      incontinence (p = 0.90). Sigmoidoscopy findings showed a nonstatistically
      significant reduction in Grade 2 or worse rectal changes from 32% with placebo to
      27% in the sucralfate group (p = 0.25). CONCLUSION: This trial demonstrated no
      statistically significant reduction in the incidence of late rectal toxicity in
      patients randomized to receive sucralfate. However, this result was considered
      inconclusive, because the trial was unable to exclude clinically important
      differences in the late toxicity rates.

PMID- 15519780
TI  - Long-term results using local excision after preoperative chemoradiation among
      selected T3 rectal cancer patients.
AB  - PURPOSE: To assess the pelvic failure among patients with T3 rectal cancer
      treated with local excision after preoperative chemoradiation. METHODS AND
      MATERIALS: Between January 1990 and June 2002, 431 patients with clinically
      staged T3 rectal cancer were treated with preoperative chemoradiation followed by
      surgical resection. Full-thickness local excision [Kraske (n = 3) or a transanal
      excision (n = 23)] was performed in 26 patients because of patient refusal of
      abdominoperineal resection (APR) (n = 13), medical comorbidity (n = 4), physician
      preference after a complete clinical response (n = 6), and other reasons (n = 3).
      All patients were treated with continuous-infusion 5-fluorouracil (5-FU) (300
      mg/m(2) Monday to Friday) and concomitant pelvic radiation (45 Gy in 25 fractions
      with a 3-field belly board technique). Ten local-excision patients received a
      concomitant boost during the last week of therapy (1.5-Gy second daily fractions)
      for a total dose of 52.5 Gy. Similar preoperative treatment was followed by total
      mesorectal excision in 405 patients. Among the local-excision patients, the
      median tumor size was 3.5 cm (range, 0.5-7 cm). Well-differentiated or moderately
      differentiated histology was present in all but 3 cases, and endoscopic
      ultrasound staging examination was performed in 25 of 26 patients. Based on CT
      findings, 1 patient was node positive. The median circumference involved by tumor
      was 33%, (20%-75%). The median distance from the anal verge was 3 cm (range, 1-8
      cm). RESULTS: The mean follow-up was 46 months (range, 5-109 months) in the local
      excision group. In the local-excision group, 19 of 26 patients had only residual
      scarring noted on digital rectal examination and rigid proctoscopy before
      surgery. Fourteen patients (54%) had a complete histologic response to
      chemoradiation, 9 patients (35%) had microscopic residual disease, and 3 patients
      (12%) had gross residual disease. Two intrapelvic recurrences occurred at 76 and
      20 months among the 26 patients treated with local excision (6% 5-year actuarial
      pelvic recurrence rate). This rate compared with an 8% 5-year actuarial pelvic
      recurrence rate among T3 patients treated with mesorectal excision and a 6%
      pelvic recurrence rate in the subgroup of mesorectal-excision patients with a
      complete clinical response to preoperative chemoradiation. One additional local
      excision patient recurred in an inguinal lymph node after local excision and
      subsequently died of metastatic disease. A total of 2 local-excision patients
      died of metastatic rectal cancer. Actuarial overall survival at 5 years was 86%
      in the local-excision group compared with 81% among mesorectal-excision patients
      (p = NS), and 85% in patients with a complete clinical response to chemoradiation
      followed by mesorectal excision by APR or LAR (p = NS). CONCLUSIONS: In an
      experience stimulated by patient refusal of APR, highly selected patients who
      responded well to conventional external-beam radiotherapy (CXRT) were selected to
      undergo local excision. Most of these patients had pathologic complete response.
      Local control and survival rates are comparable to those achieved with
      chemoradiation followed by mesorectal excision. This strategy should be
      prospectively studied in a group of patients with low rectal cancer who have no
      clinical evidence of tumor after chemoradiation.

PMID- 15519781
TI  - Predictors of acute esophagitis in patients with non-small-cell lung carcinoma
      treated with concurrent chemotherapy and hyperfractionated radiotherapy followed
      by surgery.
AB  - PURPOSE: To evaluate possible clinical and dosimetric predictors of acute
      esophagitis in patients with locally advanced non-small-cell lung carcinoma
      treated in a prospective Phase I-II trimodality protocol. METHODS AND MATERIALS:
      The data from 36 patients with Stage III non-small-cell lung carcinoma treated in
      a Phase I-II high-dose concurrent chemoradiotherapy protocol were analyzed for
      possible predictors of acute esophagitis. The median age was 58 years (range, 38
      77 years). Patients included in this study had either Stage IIIA (n = 24) or IIIB
      (n = 12) disease. All patients were treated with induction concurrent carboplatin
      (area under the plasma concentration-time curve 1), vinorelbine (5-15 mg/m(2)),
      and hyperfractionated radiotherapy (69.6 Gy) followed by consolidation
      chemotherapy (carboplatin area under the plasma concentration-time curve 6,
      vinorelbine 25 mg/m(2), docetaxel 75 mg/m(2)) or surgery (n = 19) plus
      consolidation chemotherapy. Acute toxicities were graded using the Radiation
      Therapy Oncology Group criteria. The following clinical and dosimetric parameters
      were analyzed: age, gender, race, T stage, N stage, pretreatment body mass index,
      percentage of weight lost during therapy, pretherapy serum albumin, tumor
      location, length of esophagus in treatment field, percentage of esophagus volume
      treated to >40, >45, >50, >55, >60, and >65 Gy. These parameters were coded and
      analyzed against Grade 2 and worse esophagitis using univariate and multivariate
      regression analyses. RESULTS: Of the 36 patients, Grade 1, 2, and 3 acute
      esophagitis was observed in 16 (44%), 12 (33%), and 2 (5.5%) patients,
      respectively. Grade 4 or 5 toxicity was not observed in this patient cohort. Only
      the pretreatment body mass index (rho = -0.431, p = 0.004) and percentage of
      esophagus volume treated to >50 Gy (rho = 0.297, p = 0.040) demonstrated a
      statistically significant correlation with the incidence of Grade 2 or worse
      esophagitis on univariate analysis. These parameters retained their statistical
      significance on multivariate regression analysis (p = 0.029 and 0.049,
      respectively). CONCLUSION: In patients undergoing concurrent high-dose
      chemotherapy and hyperfractionated radiotherapy, a low pretherapy body mass index
      and percentage of esophagus volume treated to >50 Gy were significantly
      associated with acute Grade 2 or worse esophagitis.

PMID- 15519782
TI  - Radiotherapy and prognostic factors for thymoma: a retrospective study of 175
      patients.
AB  - PURPOSE: To assess the factors that predict local control and survival in
      patients with thymoma treated with adjuvant radiotherapy (RT) and suggest
      strategies for optimizing adjuvant RT. METHODS AND MATERIALS: The study
      population comprised 47 patients with noninvasive thymoma and 128 patients with
      invasive thymoma. Treatment was surgery in 175 patients and radiotherapy in 169
      patients; 25 patients also received adjuvant chemotherapy. The clinical factors
      (age, histologic features, stage, presence of myasthenia gravis) and therapeutic
      factors (extent of operation, irradiation dose, and field size) were
      retrospectively recorded and accessed using multivariate analysis. RESULTS: The
      overall survival rate at 5 and 10 years was 86.4% and 80.6%, respectively. Only 2
      patients had a relapse in the noninvasive group. None died of thymoma during the
      study period. The patients with invasive disease had a 5- and 10-year disease
      free survival rate of 64.4% and 55.6%, respectively, with 24 intrathoracic
      failures, 14 extrathoracic failures, and 8 combined failures. The univariate and
      multivariate analyses showed that Mosaoka stage and extent of resection were the
      important prognostic factors for patient with invasive thymoma. The 5-year
      survival rate and local control rate was 96% and 96% for Stage II, 77.8% and
      56.4% for Stage III, 56.6% and 42.7% for Stage lVa, and 35.6% and 21.6% for Stage
      IVb (p < 0.0001 among different stage groups), respectively. The 5-year local
      control rate in patients with the tumor bed irradiated was 68.2%, comparable to
      the group treated with an extended RT field (66.6%). Age, histopathologic
      findings, radiation dose, and presence of myasthenia gravis were not
      statistically significant prognostic factors. CONCLUSION: Disease stage and
      extent of resection affected the prognosis of invasive thymoma patients.
      Extending the radiation field prophylactically was not associated with greater
      local control and is of questionable value for patients with invasive thymoma.

PMID- 15519783
TI  - Clinical results of proton beam therapy for skull base chordoma.
AB  - PURPOSE: To evaluate clinical results of proton beam therapy for patients with
      skull base chordoma. METHODS AND MATERIALS: Thirteen patients with skull base
      chordoma who were treated with proton beams with or without X-rays at the
      University of Tsukuba between 1989 and 2000 were retrospectively reviewed. A
      median total tumor dose of 72.0 Gy (range, 63.0-95.0 Gy) was delivered. The
      patients were followed for a median period of 69.3 months (range, 14.6-123.4
      months). RESULTS: The 5-year local control rate was 46.0%. Cause-specific,
      overall, and disease-free survival rates at 5 years were 72.2%, 66.7%, and 42.2%,
      respectively. The local control rate was higher, without statistical
      significance, for those with preoperative tumors <30 mL. Partial or subtotal
      tumor removal did not yield better local control rates than for patients who
      underwent biopsy only as the latest surgery. CONCLUSION: Proton beam therapy is
      effective for patients with skull base chordoma, especially for those with small
      tumors. For a patient with a tumor of <30 mL with no prior treatment, biopsy
      without tumor removal seems to be appropriate before proton beam therapy.

PMID- 15519784
TI  - Tolerability of the Intergroup 0099 (INT 0099) regimen in locally advanced
      nasopharyngeal cancer with a focus on patients' nutritional status.
AB  - PURPOSE: The Intergroup 0099 trial (INT 0099) for locally advanced nasopharyngeal
      cancer (NPC) has set a standard of practice. This retrospective review documents
      our institutional experience with this regimen. METHODS AND MATERIALS: For all
      NPC patients treated between January 1998 and December 2002 with the INT 0099
      regimen, compliance, toxicity, weight change, and feeding tube use were recorded.
      Patients were grouped by therapy completion status and by feeding tube status.
      RESULTS: Of 78 consecutive patients, 75 were evaluable. Compliance with
      radiotherapy was excellent. Only 43% and 61% of patients received all cycles of
      concurrent and adjuvant chemotherapy, respectively. Patients who successfully
      completed therapy had a higher average baseline weight and were more likely to
      have had a prophylactic feeding tube. Forty of 75 patients had a feeding tube
      inserted and were analyzed as two groups. Patients with prophylactic insertion (n
      = 23) had a more gradual drop in weight, and recovered to a greater degree at 1
      year (93.6% vs. 87.2%), than those with a feeding tube inserted therapeutically
      during treatment (n = 17). CONCLUSIONS: The INT 0099 regimen was generally
      delivered with modifications to the chemotherapy component, as in the original
      trial. The prophylactic insertion of a feeding tube may facilitate therapy
      completion and weight recovery in some patients.

PMID- 15519785
TI  - Combined treatment of anaplastic thyroid carcinoma with surgery, chemotherapy,
      and hyperfractionated accelerated external radiotherapy.
AB  - PURPOSE: To analyze a prospective protocol combining surgery, chemotherapy (CT),
      and hyperfractionated accelerated radiotherapy (RT) in anaplastic thyroid
      carcinoma. METHODS AND MATERIALS: Thirty anaplastic thyroid carcinoma patients
      (mean age, 59 years) were treated during 1990-2000. Tumor extended beyond the
      capsule gland in 26 patients, with tracheal extension in 8. Lymph node metastases
      were present in 18 patients and lung metastases in 6. Surgery was performed
      before RT-CT in 20 patients and afterwards in 4. Two cycles of doxorubicin (60
      mg/m(2)) and cisplatin (120 mg/m(2)) were delivered before RT and four cycles
      after RT. RT consisted of two daily fractions of 1.25 Gy, 5 days per week to a
      total dose of 40 Gy to the cervical lymph node areas and the superior
      mediastinum. RESULTS: Acute toxicity (World Health Organization criteria) was
      Grade 3 or 4 pharyngoesophagitis in 10 patients; Grade 4 neutropenia in 21, with
      infection in 13; and Grade 3 or 4 anemia and thrombopenia in 8 and 4,
      respectively. At the end of the treatment, a complete local response was observed
      in 19 patients. With a median follow-up of 45 months (range, 12-78 months), 7
      patients were alive in complete remission, of whom 6 had initially received a
      complete tumor resection. Overall survival rate at 3 years was 27% (95%
      confidence interval 10-44%) and median survival 10 months. In multivariate
      analysis, tracheal extension and macroscopic complete tumor resection were
      significant factors in overall survival. Death was related to local progression
      in 5% of patients, to distant metastases in 68%, and to both in 27%. CONCLUSIONS:
      Main toxicity was hematologic. High long-term survival was obtained when RT-CT
      was given after complete surgery. This protocol avoided local tumor progression,
      and death was mainly caused by distant metastases.

PMID- 15519786
TI  - Patterns of radiotherapy practice for patients with carcinoma of the uterine
      cervix: a patterns of care study.
AB  - PURPOSE: To determine the influence of research findings and evolving technology
      on the practice of radiotherapy in patients with carcinoma of the cervix. METHODS
      AND MATERIALS: Radiation oncology facilities were randomly selected from two
      strata: those that treated <500 and those that treated >/=500 new cancer patients
      annually. Patient records were randomly selected from lists of eligible patients
      treated between 1996 and 1999 at each institution. A total of 442 patient records
      were reviewed at 59 facilities (55 with eligible patients). National estimates
      were made using weights that reflected the relative contribution of each
      institution and of each patient within the sampled institutions. Most estimates
      were based on the 383 patients who had received their initial therapy at a
      surveyed facility (excluding the 59 patients who were referred for brachytherapy
      only after initial treatment at another facility). The estimates of brachytherapy
      practice were based on the 408 patients who had received their brachytherapy at a
      surveyed facility. The data were compared with those obtained from a similar 1992
      1994 survey. RESULTS: Overall, 40.5%, 25.4%, and 33.9% of patients had Stage IA
      IIA, IIB, or IIIA-IVA disease, respectively. CT was the most common method of
      nodal evaluation, with surgical evaluation performed in only 12% of patients. Of
      the 55 facilities with eligible patients, 32 had treated <==8 eligible patients
      during the 4-year study period. We estimated that 27.5% of patients were treated
      at facilities that treated <==2 patients with intact cervical cancer annually;
      43% were treated at facilities that treated <500 new patients annually. Patients
      treated at small facilities were significantly more likely to have received a
      total dose to Point A of <80 Gy, to have had their treatment protracted to >70
      days, and to have undergone adjuvant hysterectomy or chemotherapy. In large
      facilities, radiotherapy was less likely to be protracted to >70 days in the 1996
      1999 survey than in the 1992-1994 survey (p < 0.0001); however, in small
      facilities, treatment was more likely to be protracted than in the earlier survey
      (p = 0.06), contributing to increasing disparities between the treatments given
      in large and small facilities. Overall, 92.4% of patients treated with
      nonpalliative intent were treated with brachytherapy. Of the patients who
      received brachytherapy, 16.4% had at least part of their brachytherapy delivered
      at a high dose rate; this was not significantly greater than the proportion
      treated with high-dose-rate brachytherapy in the 1992-1994 survey (9.1%; p =
      0.3). The proportion of patients receiving chemotherapy as part of their initial
      treatment in 1996-1999 (34.6%) was not significantly different statistically from
      that in 1992-1994 (25.6%; p = 0.3). However, in 1999, 63% of patients had
      received chemotherapy compared with 19%, 28%, and 26% in 1996, 1997, and 1998,
      respectively. The details and confirmation of chemotherapy administration were
      rarely documented in the radiation oncology clinic notes and hospital records.
      CONCLUSION: The sharp increase in the use of chemotherapy in 1999 suggested rapid
      application of the results from randomized trials. However, considerable
      heterogeneity in practice patterns remains, particularly in the use of
      brachytherapy. The practice at small facilities appears to differ significantly
      from that at larger facilities in several respects, with a statistically
      significantly larger proportion of treatments at small facilities failing to meet
      current guidelines for optimal treatment.

PMID- 15519787
TI  - Concurrent chemotherapy and hypofractionated twice-daily radiotherapy in cervical
      cancer patients with stage IIIB disease and bilateral parametrial involvement: a
      phase I-II study.
AB  - PURPOSE: Stage IIIB cervical cancer patients with bilateral parametrial
      involvement have a poor prognosis with low survival rates. In an effort to
      improve outcome of these patients, we initiated a prospective, Phase I-II trial
      of concomitant chemotherapy with cisplatin and 5-fluorouracil and
      hypofractionated twice-daily radiotherapy. This program was initiated on the
      basis of the encouraging results obtained in the treatment of bladder cancer
      using a similar regimen. The purpose of this study was to evaluate the results of
      treatment (toxicity, survival, and patterns of failure) using this novel
      approach. METHODS AND MATERIALS: A total of 34 patients with Stage IIIB squamous
      cell cervical cancer and bilateral parametrial involvement entered the study.
      After inclusion of the first 14 patients, the study was put on hold for 6 months,
      and the patients were carefully observed. Once the toxicity level was found
      acceptable, the remaining 20 patients entered the study. External beam
      radiotherapy was delivered twice daily on Days 1 and 3, 15 and 17, 45 and 47, and
      59 and 61. The whole pelvis was treated each treatment day at a dose of 2.5 Gy
      b.i.d. Low-dose-rate brachytherapy (35 Gy to Point A) was delivered on Day 29.
      Chemotherapy was administered on Days 1-3, 15-17, 45-47, and 59-61 and consisted
      of cisplatin 15 mg/m(2) and 5-fluorouracil 400 mg/m(2). RESULTS: The treatments
      were well tolerated. None of the patients developed Grade 3-4 acute toxicity.
      Late Grade 3-4 GI or GU toxicity was seen in 4 (11.7%) and 1 (3%) patient,
      respectively. At a median follow-up of 60 months, 18 patients were alive. The 3
      year and 5-year overall survival rate was 76% and 59%, respectively. CONCLUSION:
      This protocol, comprising concomitant chemotherapy and twice-daily
      hypofractionated split-course radiotherapy was associated with moderate toxicity
      and a survival that exceeds that previously reported for this high-risk
      population.

PMID- 15519788
TI  - Proposed guidelines for image-based intracavitary brachytherapy for cervical
      carcinoma: report from Image-Guided Brachytherapy Working Group.
AB  - PURPOSE: To present issues to be considered in, and make proposals for, image
      based brachytherapy for cervical cancer. METHODS AND MATERIALS: The Image-Guided
      Brachytherapy Working Group, consisting of representatives from the Gynecology
      Oncology Group (GOG), Radiologic Physics Center (RPC), American Brachytherapy
      Society (ABS), American College of Radiology (ACR), American College of Radiology
      Imaging Network (ACRIN), American Association of Physicists in Medicine (AAPM),
      Radiation Therapy Oncology Group (RTOG), and American Society for Therapeutic
      Radiology and Oncology (ASTRO), proposed guidelines for image-based brachytherapy
      for cervical cancer. This report was based on their aggregate clinical experience
      and a review of the literature. It reflects only the personal opinions of the
      authors and is not meant to be an endorsement from any of the above
      organizations. RESULTS: The Group recommended T(2)-weighted MRI using a pelvic
      surface coil with MRI-compatible brachytherapy applicators in place for image
      based intracavitary brachytherapy for cervical cancer. Imaging must be performed
      with the patient in the treatment position, with all other treatment conditions
      duplicated as closely as possible. Future use of positron emission tomography or
      positron emission tomography/CT may obviate the need for special applicators. The
      group proposed the following terminology for image-based brachytherapy. The
      GTV((I)) is defined as the gross tumor volume as defined through imaging, GTV is
      defined as the GTV((I)) plus any clinically visualized or palpable tumor
      extensions, and GTV + cx is defined as the GTV plus the entire cervix. The dose
      volume histograms (DVH) of the GTV, GTV((I)), GTV + cx should be performed, and
      the dose to 100%, 95%, or 90% of the GTV (D(100), D(95), and D(90), respectively)
      and the percentage of the GTV covered by Point A dose (V(100)) should be
      reported. Similarly, the DVH of the bladder and rectum wall should be performed,
      and the maximal dose at any point within the bladder and rectal wall should be
      reported, along with the maximal dose to a contiguous 1, 2, and 5 cm(3) volume of
      the bladder and rectum, respectively. In addition, the dose at the International
      Commission on Radiation Units and Measurements reference point for the bladder
      and rectum should be reported. The Group thought that the current dose
      prescription method in use for cervical cancer brachytherapy (i.e., to prescribe
      to Point A in most institutions) should not be changed as yet, because image
      based dosimetry is not ready for routine practice. The Group proposes that for
      research purposes, individual centers and cooperative groups (e.g., GOG, RTOG,
      ACRIN) collect image-based dosimetry information and perform DVHs and correlate
      these data with the clinical outcome to determine which of the above parameters
      are relevant. The Group encourages external funding for image-based dosimetry and
      recommends that brachytherapy manufacturers develop image-compatible applicators.
      CONCLUSION: Although current institutional brachytherapy prescription for
      cervical cancer should continue, image-based data collection and analysis are
      needed to optimize cervical cancer brachytherapy. Proposals are made for research
      in image-based brachytherapy for cervical cancer.

PMID- 15519789
TI  - High-dose-rate brachytherapy alone versus whole breast radiotherapy with or
      without tumor bed boost after breast-conserving surgery: seven-year results of a
      comparative study.
AB  - PURPOSE: To report the 7-year results of a prospective study of accelerated
      partial breast irradiation (APBI) using interstitial high-dose-rate brachytherapy
      and compare the treatment results with those achieved by standard, whole breast
      radiotherapy (WBRT), with or without a tumor bed boost (TBB). METHODS AND
      MATERIALS: Between 1996 and 1998, 45 prospectively selected patients with T1N0
      N1mi (single nodal micrometastasis), nonlobular breast cancer without the
      presence of an extensive intraductal component and with negative surgical margins
      were treated with APBI using interstitial high-dose-rate implants. A total dose
      of 30.3 Gy (n = 8) and 36.4 Gy (n = 37) in seven fractions within 4 days was
      delivered to the tumor bed plus a 1-2-cm margin. During the same period, 80
      patients, who met the eligibility criteria for APBI but who were treated with 50
      Gy WBRT with (n = 36) or without (n = 44) a 10-16-Gy TBB, were selected as
      controls. The median follow-up for the APBI and control groups was 81 and 83
      months, respectively. Local control, relapse-free survival, cancer-specific
      survival, late side effects, and cosmetic results were assessed. RESULTS: The
      crude rate of total ipsilateral breast failure was 6.7% (3 of 45), 11.4% (5 of
      44), and 8.3% (3 of 36) for patients treated with APBI, WBRT, and WBRT + TBB,
      respectively. The differences in the 5- and 7-year actuarial rates of ipsilateral
      breast recurrence were not statistically significant among patients treated with
      APBI (4.4% and 9.0%), WBRT (4.7% and 14.8%), and WBRT + TBB (5.7% and 9.5%). No
      statistically significant difference in either the 7-year probability of relapse
      free survival (79.8%, 73.5%, and 77.7% for APBI, WBRT, and WBRT + TBB,
      respectively) or cancer-specific survival (93.3%, 92.9%, and 93.9% for APBI,
      WBRT, and WBRT + TBB, respectively) was found. The 7-year actuarial elsewhere
      breast failure rate was 9.0% in the APBI group and 8.3% in the control group (p =
      0.80). The rate of excellent/good cosmetic results was 84.4% in the APBI group
      and 68.3% in the control group (p = 0.04). The corresponding rates of
      asymptomatic fat necrosis were 20.0% and 20.6%. Symptomatic fat necrosis occurred
      in 1 patient (2.2%) treated with APBI. The incidence of Grade 2 or worse late
      radiation side effects was similar for both groups (26.7% vs. 28.6%). CONCLUSION:
      Accelerated partial breast irradiation using interstitial high-dose-rate
      implants, with proper patient selection and quality assurance, yields similar 7
      year results to those achieved with standard breast-conserving therapy. APBI does
      not increase the risk of elsewhere breast failures.

PMID- 15519790
TI  - Postmastectomy CT-based electron beam radiotherapy: dosimetry, efficacy, and
      toxicity in 118 patients.
AB  - PURPOSE: To evaluate the technique, dosimetry, acute and late toxicity, local
      control (LC), and overall survival (OS) with the use of computed tomography (CT)
      based postmastectomy electron beam therapy (PMEBT) in high-risk patients. METHODS
      AND MATERIALS: From 1990 to 2000, 118 patients with pathologic stage I-IIIB
      breast cancer underwent PMEBT of the chest wall (CW) (n = 3), CW and
      supraclavicular fossa (SCV) (n = 63), CW, SCV, and internal mammary lymph nodes
      (IMN) (n = 51), and SCV+IMN (n = 1). Radiation therapy was delivered with an en
      face electron beam with a custom cutout. Treatment plans were all CT-based. The
      plans of 16 patients were retrospectively reviewed to analyze dosimetry data. A
      retrospective chart review was conducted to assess acute and late complications,
      LC, and OS. RESULTS: At a median follow-up of 43 months, 5-year LC and OS were
      91% and 61%, respectively. Sixty-one patients developed acute grade 3-4 skin
      toxicity, necessitating treatment breaks in 33 patients. Fifteen patients
      experienced a worsening of lymphedema, and 2 patients developed cardiac injury
      thought to be unrelated to radiotherapy. No patients developed symptomatic
      pneumonitis. Dosimetric analysis revealed heart and lung normal tissue
      complication probabilities of zero. Analysis of other clinically relevant
      dosimetric parameters revealed PMEBT to be comparable to previously reported
      techniques. CONCLUSION: Postmastectomy electron beam therapy is an effective way
      to deliver radiation to the postmastectomy chest wall and adjacent nodal sites.
      It offers acceptable acute and late toxicities and a high degree of local control
      given the high-risk population to which it is offered.

PMID- 15519791
TI  - Postmastectomy electron-beam chest-wall irradiation in women with breast cancer.
AB  - PURPOSE: This retrospective study evaluates the results of postmastectomy
      electron-beam chest-wall irradiation in patients with breast cancer. METHODS AND
      MATERIALS: From 1980 to 1994, 144 women with localized breast cancer received
      postmastectomy radiotherapy. The chest wall was irradiated by electron beam, 6 to
      12 MeV energy, depending on wall thickness, 2.0 Gy daily, 5 times/week for total
      dose of 50 Gy. Forty-one patients received 16-Gy boosts to the mastectomy scar.
      In addition, the supraclavicular and axilla areas were irradiated by anterior
      field with 6-MV photon beam. RESULTS: Median follow-up was 84 months. Fifteen
      patients (10%) had local-regional recurrence (LRR) and 57 patients (40%) had
      systemic relapse (SR). Median time from mastectomy to LRR was 20 months and
      median time to SR was 33 months. Axillary lymph nodes status influenced both LRR
      and SR. LRR rate was 0% in N0 and 12% in N1 disease; SR rate was 14% in N0 and
      45% in N1 disease. Disease-free and overall survival was 58% and 67% in 10 years
      and 50% and 55% in 20 years, respectively. No cardiac toxicity was related to
      left chest-wall irradiation. CONCLUSION: Postmastectomy electron-beam chest-wall
      irradiation is as effective as photon-beam irradiation in breast cancer.

PMID- 15519792
TI  - Cardiac chamber and coronary artery doses associated with postmastectomy
      radiotherapy techniques to the chest wall and regional nodes.
AB  - PURPOSE: To compare the estimated radiation doses delivered to the cardiac
      chambers (CC) and coronary arteries (CA) for 5 postmastectomy radiotherapy (PMRT)
      techniques. METHODS AND MATERIALS: A dosimetry study of 20 left-sided PMRT cases
      was conducted. Cardiac chambers (left and right atria [LA/RA] and left and right
      ventricles [LV/RV]) and coronary vessels (left main [LM], left anterior
      descending [LAD], left circumflex [LCX], right coronary [RCA] and posterior
      descending [PDA] arteries) were contoured on contrast-enhanced CT scans and
      verified by a cardiologist (T.K.). Five PMRT techniques were applied to each
      case; 50 Gy in 2 Gy fractions was delivered to the chest wall +/- internal
      mammary node targets. The techniques were: (1) standard tangents (TAN); (2)
      cobalt (Co); (3) reverse hockey stick (RHS); (4) mixed photon/electron beam
      (20/80); and (5) partially wide tangent fields (PWTF). Three-dimensional dose
      calculations for 100 plans were performed for all structures. Plans were compared
      by using the mean dose (Dmean) and the volume that received more than 30 Gy
      (V(30)) and 45 Gy (V(45)) for each structure. RESULTS: Cobalt and 20/80
      techniques delivered higher Dmeans to the whole heart and individual cardiac
      chambers (RA, RV, LA, and LV) as compared with the other three techniques. The
      heart received a Dmean of 21.03 +/- 3.5 Gy from Co and 11.87 +/- 5.22 Gy from
      20/80. The remaining techniques delivered heart Dmeans of 2.90-4.94 Gy. When
      V(30) was used as a metric, all techniques had comparably low V(30) to the heart,
      except for Co, which resulted in a significantly higher irradiated volume of
      right-sided cardiac chambers (59.06% +/- 30.7 for RA F-test < 0.0001; and 61.46%
      +/- 22.13 for RV, F-test < 0.0001). Dmean to the proximal LAD (LAD_p) was
      significantly higher for RHS (17.64 +/- 7.43 Gy) and 20/80 (20.52 +/- 8.36 Gy)
      and lowest for PWTF (9.5 +/- 4.16 Gy). The Dmean for the distal LAD (LAD_d) was
      significantly lower with PWTF (11.02 +/- 7.34 Gy) than with all other techniques,
      including TAN (p < 0.0001). Similar results for PWTF and TAN were observed when
      V30 and V45 were used. CONCLUSIONS: Cardiac substructures receive the most
      radiation exposure after PMRT with CO, 20/80 or both and least exposure with
      PWTF. Although TAN resulted in significant sparing of the majority of the cardiac
      structures, a significantly higher dose and volume of LAD was exposed when
      compared with PWTF. Although the clinical relevance of these dose differences is
      not clearly understood, these dosimetric estimates can serve as a baseline in the
      development of new techniques for locoregional treatment that will further reduce
      cardiac exposure.

PMID- 15519793
TI  - Impact of radiation oncology practice on pain: a cross-sectional survey.
AB  - PURPOSE: A cross-sectional study was performed to evaluate the prevalence of pain
      in our radiotherapy (RT) department. The impact of RT practice on pain and pain
      management were analyzed. METHODS AND MATERIALS: Of 126 patients, 93 (73.8%)
      completed the questionnaire proposed in this survey. It was designed to assess
      the proportion of patients experiencing pain in the department, the impact of RT
      practice on pain, and patients' estimate of the quality of management of their
      pain by the medical staff. Pain intensity and patient satisfaction were assessed
      using an 11-point numeric rating scale. RESULTS: Of the 93 patients, 66
      experienced pain during RT, 13 of whom were totally relieved by analgesic
      treatment. The mean pain intensity was 3.9 (SD 2.3). A total of 26 patients had a
      numeric rating >/=4, indicating that their pain was not sufficiently treated. The
      objective length of waiting time for a session, transportation, and mobilization
      for session positioning worsened the pain of a substantial proportion of
      patients. A total of 56% of patients had a favorable opinion about pain
      management in our department. A high percentage (72.2%) of patients found that
      the time spent by the medical staff for pain management was inadequate, and 54.5%
      believed that the psychological support they received was insufficient. Personnel
      in the RT department remained the primary source of information regarding pain
      control. However, 17.5% of patients did not report their pain or talked about it
      to non-health care professionals. CONCLUSION: The prevalence of pain was high in
      the department. The specific practice of RT worsened pain and nearly one-half of
      patients were not satisfied with its management. The necessity for medical staff
      to be more available was highlighted by patients.

PMID- 15519794
TI  - Efficacy of orgotein in prevention of late side effects of pelvic irradiation: a
      randomized study.
AB  - PURPOSE: To study whether orgotein is effective in preventing late radiation
      induced effects. METHODS AND MATERIALS: Patients >18 years old who were diagnosed
      with rectal cancer, had an indication for pelvic irradiation (RT) after surgery,
      and complied with the selection criteria were randomly assigned at the end of RT
      to receive orgotein for 7 weeks or no treatment (control). The Radiation Therapy
      Oncology Group toxicity scale was used to evaluate the RT-induced side effects
      for up to 2 years. Interruptions due to toxicity, concomitant medication, and non
      RT adverse events were also recorded. RESULTS: A total of 100 patients were
      included, with 50 in each group. The groups were comparable in terms of the
      demographic and baseline characteristics. The orgotein group had statistically
      significant less late toxicity than the control group (p = 0.036) and nontreated
      patients had a 66% greater chance of developing late toxicity at 2 years.
      Grouping toxicity as nonrelevant (Radiation Therapy Oncology Group Grade 0-1) and
      relevant (Grade 2 or worse), patients given orgotein had a lower incidence of
      late relevant toxicity than did controls, with statistical significance reached
      at all follow-up visits. After 2 years, patients not treated with orgotein had,
      in general, a 37% greater chance of developing late relevant toxicity; this risk
      was 26% when referring specifically to GI toxicity. No adverse events
      attributable to orgotein were recorded at any time during the study. CONCLUSION:
      Orgotein is a safe treatment that significantly prevents the overall occurrence
      of late toxicity, with toxicity reduction particularly evident in the lower GI
      tract.

PMID- 15519795
TI  - Triple combination of irradiation, chemotherapy (pemetrexed), and VEGFR
      inhibition (SU5416) in human endothelial and tumor cells.
AB  - PURPOSE: This is the first preclinical report evaluating a trimodal therapy
      consisting of irradiation, chemotherapy, and antiangiogenesis in the context of a
      multimodal anticancer strategy. The combination of the folate antimetabolite
      pemetrexed, SU5416, a receptor tyrosine kinase inhibitor of VEGFR2, and
      irradiation was investigated in human endothelial cells and tumor cell lines.
      METHODS AND MATERIALS: Primary isolated human umbilical vein endothelial cells
      (HUVEC), human dermal microvascular endothelial cells (HDMEC), and human
      glioblastoma (U87) and prostate cancer cells (PC3) were exposed to pemetrexed (2
      h) alone and in combination with SU5416 (2 h). When combined with irradiation up
      to 8 Gy, fixed concentrations of pemetrexed (1.06 muM) and SU5416 (1.0 muM) were
      used. Proliferation and clonogenic assays were conducted with endothelial and
      tumor cells. The migration/invasion ability of endothelial cells and the ability
      to produce tubular structures were tested in Matrigel and tube formation assays.
      Apoptosis was measured by sub-G1 DNA and caspase-3 flow cytometry. To investigate
      underlying cell signaling, immunocytochemistry was used to detect Akt survival
      signaling involvement. RESULTS: Triple combination using only a low-toxicity drug
      exposure of pemetrexed and SU5416 results in greater response than each treatment
      alone or than each combination of two modalities in all tested endothelial and
      tumor cell models. Triple combination substantially inhibits proliferation,
      migration/invasion, tube formation, and clonogenic survival. Triple combination
      also induced the highest rate of apoptosis in HDMEC and HUVEC as indicated by sub
      1 G1 and caspase-3 assessment. Interestingly, triple combination therapy also
      reduces proliferation and clonogenic survival significantly in U87 and PC3 tumor
      cell lines. SU5416 potently inhibited Akt phosphorylation which could be induced
      by radiation and radiochemotherapy in human endothelial cells. CONCLUSIONS: Our
      findings demonstrate the high antiendothelial/antitumoral efficacy of the
      concurrent administration of irradiation, chemotherapy, and angiogenesis
      inhibition in vitro. A potential explanation for the favorable combination would
      be that VEGF signaling inhibition downregulates Akt survival signaling upon
      activation by radiation and/or chemotherapy. The data also suggest that
      endothelial cell apoptosis may have an important role in the benefits of the
      presented therapy.

PMID- 15519796
TI  - Efficacy of combined antiangiogenic and vascular disrupting agents in treatment
      of solid tumors.
AB  - PURPOSE: To evaluate the antitumor efficacy of a vascular targeting strategy that
      combines an agent that disrupts established tumor blood vessels (ZD6126) with one
      that interferes with new vessel formation (ZD6474) in models of human renal cell
      carcinoma (Caki-1) and Kaposi's sarcoma (KSY-1). METHODS AND MATERIALS: Caki-1
      and KSY-1 xenograft-bearing nude mice were treated with ZD6126 and ZD6474 either
      as single agents or in combination when the tumors reached a size of
      approximately 200 mm(3). ZD6126 therapy consisted of three doses of 100 mg/kg
      administered 1, 3, and 5 days after the tumor reached the starting size. ZD6474
      was administered daily (25 mg/kg) on Days 1-5. In the combination studies, ZD6474
      treatment began immediately after the first dose of ZD6126. The tumor response to
      treatment was evaluated using a regrowth delay endpoint. RESULTS: Significant
      tumor growth delays were observed in both tumor models with either agent with the
      treatment regimen used. In the Caki-1 and KSY-1 models, respectively, ZD6126
      treatment resulted in a tumor growth delay of 23 and 26 days and ZD6474 produced
      a tumor growth delay of 24.5 and 14.5 days. When ZD6126 and ZD6474 were combined,
      the tumor growth delays increased to 55 (Caki-1) and 86 (KSY-1) days. In the KSY
      1 model, the combination therapy also resulted in 3 of 8 long-term tumor-free
      survivors. CONCLUSION: These results indicate that statistically significant
      antitumor efficacy can be achieved using a treatment strategy that combines a
      therapy that targets the established tumor blood vessels with one that interferes
      with the process of angiogenesis.

PMID- 15519797
TI  - A challenge to traditional radiation oncology.
AB  - PURPOSE: To investigate and compare the biologically effective doses, equivalent
      doses in 2-Gy fractions, log tumor cells killed, and late effects that can be
      estimated for the large fractions in short overall times that are now being
      delivered in various clinically used schedules in several countries for the
      treatment of cancer in human lungs, liver, and kidney. METHODS AND MATERIALS:
      Linear quadratic (LQ) modeling is employed with only the standard assumptions
      that tumor alpha/beta ratio is 10 Gy, pneumonitis and late complication
      alpha/beta ratios are 3 Gy, that intrinsic radiosensitivity of tumor cells is
      0.35 ln/Gy, that no tumor repopulation occurs within 2 weeks, and that LQ
      modeling is valid up to 23 Gy per fraction. As well as the planning target volume
      (PTV), we propose a practical term called the prescription isodose volume (PIV)
      to be used in this discussion. In the ideal case of 100% conformity, PIV equals
      PTV, but usually PIV is larger than the PTV. Biologically effective doses (BED)
      in Gy(10) for tumors or Gy(3) for normal lung are calculated and converted to
      equivalent doses in 2 Gy fractions (= normalized total doses [NTD]), and to
      estimated log cell kill. How such large biologic doses might be delivered to
      tissues is discussed. RESULTS: Tumor cell kill varies between 16 and 27 logs to
      base 10 for schedules from 4F x 12 Gy to 3F x 23 Gy. The rationale for the high
      end of this scale is the possible presence of hypoxic or otherwise
      extraordinarily resistant cells, but how many tumors and which ones require such
      doses is not known. How can such large doses be tolerated? In "parallel type
      organs," it is shown to be theoretically possible, provided that suitably small
      volumes are irradiated, with rapid fall-off of dose outside the PTV, and a mean
      dose (excluding PTV and allowing for local fraction size) to both lungs of less
      than 19 Gy NTD. If suitably small PTVs were used, local late BEDs have been given
      which were as large as 600 Gy(3), equivalent to 2 Gy x 180F = 360 Gy in 2-Gy
      fractions, with remarkably few complications reported clinically. Questions of
      concurrent chemotherapy and microscopic extension of lung tumor cells are
      discussed briefly. CONCLUSIONS: Such large doses can apparently be given, with
      suitable precautions and experience. Ongoing clinical trials from an increasing
      number of centers will be reporting the results of tumor control and
      complications from this new modality of biologically higher doses.

PMID- 15519798
TI  - Modulation of rodent spinal cord radiation tolerance by administration of
      platelet-derived growth factor.
AB  - PURPOSE: To examine the role of platelet-derived growth factor (PDGF) for
      ameliorating radiation myelopathy of the cervical spinal cord in a rodent model.
      METHODS AND MATERIALS: After developing the technique for cannulation of the
      basal cistern, initial animal experiments were conducted to test the feasibility
      of intrathecal continuous infusion of PDGF in a model of cervical spinal cord
      irradiation in adult Fisher F-344 rats and to determine the most effective dose
      level of PDGF. Subsequently, the dose-modification factor was determined in a
      larger group of rats. Irradiation was given in 2 fractions (16 Gy followed by 14
      24 Gy) and animals were examined for the development of paresis. RESULTS: The
      initial dose-finding experiment revealed significant differences in the incidence
      of radiation myelopathy (100% in saline-treated control rats, 25% with the most
      effective dose of PDGF, up to 100% with less effective doses). The most effective
      dose of PDGF was 0.014 mug per day. Subsequent experiments revealed a median
      effective dose (ED(50)) of 35.6 Gy (95% confidence interval, 34.7-36.5 Gy) for
      animals receiving this dose of PDGF in contrast to 33.8 Gy (33.4-34.3 Gy) for the
      control group (p = 0.003). The dose-modification factor obtained with this dose
      of PDGF was 1.05. CONCLUSIONS: Intrathecal administration of PDGF concomitant to
      irradiation of the cervical spinal cord in rats was feasible. Treatment with PDGF
      significantly increased the tolerance of the spinal cord. The PDGF experiments
      should be viewed as a proof of principle that brief therapeutic intervention in
      the earliest phase of damage induction can reduce late effects in the spinal
      cord. They form the basis for further studies of growth factor administration in
      this particular model.

PMID- 15519799
TI  - Effect of pH on radiation-induced p53 expression.
AB  - PURPOSE: In most tumors, the intratumor environment is acidic. The purpose of
      this study was to elucidate the effect of acidic extracellular environment on the
      radiation-induced expression of p53 and related molecular signals. METHODS AND
      MATERIALS: Cultured RKO.C human colorectal cancer cells carrying wild-type p53
      were used. Cells grown in pH 7.5 medium or pH 6.6 medium were irradiated with
      gamma-rays, and the expression of p53 and p53 mRNA, as well as the degradation
      rate of the molecules, was determined. The transcriptional activity for p53 was
      investigated using cells transfected with a p53 reporter construct. The
      expression of Mdm2 and the phosphorylation of p53, essential factors for p53
      degradation, were also investigated. RESULTS: The pH 6.6 environment prolonged
      the radiation-induced expression of p53 and p53 mRNA. The radiation-induced
      increase in transcriptional activity of p53 lasted longer in pH 6.6 medium than
      in pH 7.5 medium. The degradation of p53 was delayed at pH 6.6. The radiation
      induced expression of Mdm2 was markedly suppressed, whereas the phosphorylation
      of p53 was markedly increased after irradiation in pH 6.6 medium. CONCLUSION:
      Acidic environment significantly enhances the radiation-induced expression of
      p53, partly by increasing the formation of p53 and also partly by slowing down
      the degradation of p53 through inhibiting p53-Mdm2 complex formation. The
      potential implication of acidic intratumor microenvironment for the response of
      tumors to radiotherapy remains to be elucidated.

PMID- 15519800
TI  - Defining a radiotherapy target with positron emission tomography.
AB  - PURPOSE: F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) imaging
      is now considered the most accurate clinical staging study for non-small-cell
      lung cancer (NSCLC) and is also important in the staging of multiple other
      malignancies. Gross tumor volume (GTV) definition for radiotherapy, however, is
      typically based entirely on computed tomographic data. We performed a series of
      phantom studies to determine an accurate and uniformly applicable method for
      defining a GTV with FDG-PET. METHODS AND MATERIALS: A model-based method was
      tested by a phantom study to determine a threshold, or unique cutoff of
      standardized uptake value based on body weight (standardized uptake value [SUV])
      for FDG-PET based GTV definition. The degree to which mean target SUV, background
      FDG concentration, and target volume influenced that GTV definition were
      evaluated. A phantom was constructed consisting of a 9.0-L cylindrical tank.
      Glass spheres with volumes ranging from 12.2 to 291.0 cc were suspended within
      the tank, with a minimum separation of 4 cm between the edges of the spheres. The
      sphere volumes were selected based on the range of NSCLC patient tumor volumes
      seen in our clinic. The tank and spheres were filled with a variety of known
      concentrations of FDG in several experiments and then scanned using a General
      Electric Advance PET scanner. In the initial experiment, six spheres with
      identical volumes were filled with varying concentrations of FDG (mean SUV = 1.85
      approximately 9.68) and suspended within a background bath of FDG at a similar
      concentration to that used in clinical practice (0.144 muCi/mL). The second
      experiment was identical to the first, but was performed at 0.144 and 0.036
      muCi/mL background concentrations to determine the effect of background FDG
      concentration on sphere definition. In the third experiment, six spheres with
      volumes of 12.2 to 291.0 cc were filled with equal concentrations of FDG and
      suspended in a standard background FDG concentration of 0.144 muCi/mL. Sphere
      images in each experiment were auto-contoured (simulating a GTV) using the
      threshold SUV that yielded a volume matching that of the known sphere volume. A
      regressive function was constructed to represent the relationship between the
      threshold SUV and the mean target SUV. This function was then applied to define
      the GTV of 15 NSCLC patients. The GTV volumes were compared to those determined
      by a fixed image intensity threshold proposed by other investigators. RESULTS:
      There was a strong linear relationship between the threshold SUV and the mean
      target SUV. The linear regressive function derived was: threshold SUV = 0.307 x
      (mean target SUV) + 0.588. The background concentration and target volume
      indirectly affect the threshold SUV by way of their influence on the mean target
      SUV. We applied the linear regressive function, as well as a fixed image
      intensity threshold (42% of maximum intensity) to the sphere phantoms and 15
      patients with NSCLC. The results indicated that a much smaller deviation occurred
      when the threshold SUV regressive function was utilized to estimate the phantom
      volume as compared to the fixed image intensity threshold. The average absolute
      difference between the two methods was 21% with respect to the true phantom
      volume. The deviation became even more pronounced when applied to true patient
      GTV volumes, with a mean difference between the two methods of 67%. This was
      largely due to a greater degree of heterogeneity in the SUV of tumors over
      phantoms. CONCLUSIONS: An FDG-PET-based GTV can be systematically defined using a
      threshold SUV according to the regressive function described above. The threshold
      SUV for defining the target is strongly dependent on the mean target SUV of the
      target, and can be uniquely determined through the proposed iteration process.

PMID- 15519801
TI  - Four-dimensional CT scans for treatment planning in stereotactic radiotherapy for
      stage I lung cancer.
AB  - PURPOSE: Hypofractionated stereotactic radiotherapy (SRT) for Stage I non-small
      cell lung cancer requires that meticulous attention be paid toward ensuring
      optimal target definition. Two computed tomography (CT) scan techniques for
      defining internal target volumes (ITV) were evaluated. METHODS AND MATERIALS: Ten
      consecutive patients treated with SRT underwent six "standard" rapid multislice
      CT scans to generate an ITV(6 CT) and one four-dimensional CT (4DCT) scan that
      generated volumetric datasets for 10 phases of the respiratory cycle, all of
      which were used to generate an ITV(4DCT). Geometric and dosimetric analyses were
      performed for (1) PTV(4DCT), derived from the ITV(4DCT) with the addition of a 3
      mm margin; (2) PTV(6 CT), derived from the ITV(6 CT) with the addition of a 3-mm
      margin; and (3) 6 PTV(10 mm), derived from each separate GTV(6 CT), to which a
      three-dimensional margin of 10 mm was added. RESULTS: The ITV(4DCT) was not
      significantly different from the ITV(6 CT) in 8 patients, but was considerably
      larger in 2 patients whose tumors exhibited the greatest mobility. On average,
      the ITV(6 CT) missed on average 22% of the volume encompassing both ITVs, in
      contrast to a corresponding mean value of only 8.3% for ITV(4DCT). Plans based on
      PTV(4DCT) resulted in coverage of the PTV(6 CT) by the 80% isodose in all
      patients. However, plans based on use of PTV(6 CT) led to a mean PTV(4DCT)
      coverage of only 92.5%, with a minimum of 77.7% and 77.5% for the two most mobile
      tumors. PTVs derived from a single multislice CT expanded with a margin of 10 mm
      were on average twice the size of PTVs derived using the other methods, but still
      led to an underdosing in the two most mobile tumors. CONCLUSIONS: Individualized
      ITVs can improve target definition for SRT of Stage I non-small-cell lung cancer,
      and use of only a single CT scan with a 10-mm margin is inappropriate. A single
      4D scan generates comparable or larger ITVs than are generated using six
      unmonitored rapid CT scans, a finding related to the ability to account for all
      respiration-correlated mobility.

PMID- 15519802
TI  - Correlation of gross tumor volume excursion with potential benefits of
      respiratory gating.
AB  - PURPOSE: To test the hypothesis that the magnitude of thoracic tumor motion can
      be used to determine the desirability of respiratory gating. METHODS AND
      MATERIALS: Twenty patients to be treated for lung tumors had computed tomography
      image data sets acquired under assisted breath hold at normal inspiration (100%
      tidal volume), at full expiration (0% tidal volume), and under free breathing. A
      radiation oncologist outlined gross tumor volumes (GTVs) on the breath-hold
      computed tomographic images. These data sets were registered to the free
      breathing image data set. Two sets of treatment plans were generated: one based
      on an internal target volume explicitly formed from assessment of the excursion
      of the clinical target volume (CTV) through the respiratory cycle, representing
      an ungated treatment, and the other based on the 0% tidal volume CTV,
      representing a gated treatment with little margin for residual motion. Dose
      volume statistics were correlated to the magnitude of the motion of the center of
      the GTV during respiration. RESULTS: Patients whose GTVs were >100 cm(3) showed
      little decrease in lung dose under gating. The other patients showed a
      correlation between the excursion of the center of the GTV and a reduction in
      potential lung toxicity. As residual motion increased, the benefits of
      respiratory gating increased. CONCLUSION: Gating seems to be advantageous for
      patients whose GTVs are <100 cm(3) and for whom the center of the GTV exhibits
      significant motion, provided residual motion under gating is kept small.

PMID- 15519803
TI  - Correlation of lung tumor motion with external surrogate indicators of
      respiration.
AB  - PURPOSE: To assess the correlation of respiratory volume and abdominal
      displacement with tumor motion as seen with X-ray fluoroscopy. Measurements
      throughout the patient's treatment course allowed an assessment of the
      interfractional reproducibility of this correlation. METHODS AND MATERIALS: Data
      were acquired from 11 patients; 5 were studied over multiple days. Measurements
      of respiratory volume by spirometry and abdominal displacement by a real-time
      position tracking system were correlated to simultaneously acquired X-ray
      fluoroscopy measurements of superior-inferior tumor displacement. The linear
      correlation coefficient was computed for each data acquisition. The phase
      relationship between the surrogate and tumor signals was estimated through cross
      correlation delay analysis. RESULTS: Correlation coefficients ranged from very
      high to very low (0.99-0.39, p < 0.0001). The correlation between tumor
      displacement and respiratory volume was higher and more reproducible from day to
      day than between tumor displacement and abdominal displacement. A nonzero phase
      relationship was observed in nearly all patients (-0.65 to +0.50 s). This
      relationship was observed to vary over inter- and intrafractional time scales.
      Only 1 of 5 patients studied over multiple days had a consistent relationship
      between tumor motion and either surrogate. CONCLUSIONS: Respiratory volume has a
      more reproducible correlation with tumor motion than does abdominal displacement.
      If forming a tumor-surrogate prediction model from a limited series of
      observations, the use of surrogates to guide treatment might result in geographic
      miss.

PMID- 15519804
TI  - Reproducibility of organ position using voluntary breath-hold method with
      spirometer for extracranial stereotactic radiotherapy.
AB  - PURPOSE: To evaluate in healthy volunteers the reproducibility of organ position
      using a voluntary breath-hold method with a spirometer and the feasibility of
      this method for extracranial stereotactic radiotherapy in a clinical setting.
      METHODS AND MATERIALS: For this study, 5 healthy volunteers were enrolled. After
      training sessions, they held their breath at the end-inspiration and the end
      expiration phase under spirometer-based monitoring. Computed tomography (CT)
      scans were performed twice at each respiratory phase, with a 10-min interval, on
      2 separate days. The total number of CT scans was four at each respiratory phase.
      After CT volume data were transferred to a three-dimensional treatment-planning
      system, digitally reconstructed radiographs (DRRs) were calculated for anterior
      posterior and left-right beams. Verification was performed with DRRs relative to
      the diaphragm position, bony landmarks, and the isocenter in each healthy
      volunteer at each respiratory phase. To evaluate intrafraction reproducibility,
      we measured the distance between diaphragm position and bony landmarks. To
      evaluate interfraction reproducibility, we measured the distance between
      diaphragm position and the isocenter. Reproducibility and setup error were
      defined as the average value of the differences between each DRR with regard to
      the first DRR. RESULTS: Intrafraction reproducibility of the caudal-cranial
      direction was 4.0 +/- 3.5 mm at the end-inspiration phase and 2.2 +/- 2.0 mm at
      the end-expiration phase. Interfraction reproducibility of the caudal-cranial
      direction was 5.1 +/- 4.8 mm at the end-inspiration phase and 2.1 +/- 1.8 mm at
      the end-expiration phase. The end-expiration phase was more stable than the end
      inspiration phase. CONCLUSIONS: The voluntary breath-hold method with a
      spirometer is feasible, with relatively good reproducibility. We are encouraged
      about the use of this technique clinically for extracranial stereotactic
      radiotherapy.

PMID- 15519805
TI  - Dose conformation of intensity-modulated stereotactic photon beams, proton beams,
      and intensity-modulated proton beams for intracranial lesions.
AB  - PURPOSE: This study evaluates photon beam intensity-modulated stereotactic
      radiotherapy (IMSRT) based on dynamic leaf motion of a micromultileaf collimator
      (mMLC), proton beams, and intensity-modulated proton therapy (IMPT) with respect
      to target coverage and organs at risk. METHODS AND MATERIALS: Dose plans of 6
      stereotactically treated patients were recalculated for IMSRT by use of the same
      field setup and an inverse planning algorithm. Proton and IMPT plans were
      calculated anew. Three different tumor shapes, multifocal, ovoid, and irregular,
      were analyzed, as well as dose to organs-at-risk (OAR) in the vicinity of the
      planning target volume (PTV). Dose distributions were calculated from beam-setup
      data for a manual mMLC for stereotactically guided conformal radiotherapy (SCRT),
      a dynamic mMLC for IMSRT, the spot-scanning technique for protons, and a modified
      spot-scanning technique for IMPT. SCRT was included for a part of the comparison.
      Criteria for assessment were PTV coverage, dose-volume histograms (DVH), volumes
      of specific isodoses, and the dose to OAR. RESULTS: Dose conformation to the PTV
      is equally good for all three techniques and tumor shapes considered. The volumes
      of the 90% and 80% isodose were comparable for all techniques. For the 50%
      isodose volume, a divergence between the two modes was seen. In 3 cases, this
      volume is smaller for IMSRT, and in the 3 other cases, it is smaller for IMPT.
      This difference was even more pronounced for the volumes of the 30% isodose; IMPT
      shows further improvement over conventional protons. OAR in concavities (e.g.,
      the brainstem) were similarly well spared by protons and IMSRT. IMPT spares
      critical organs best. Fewer proton beams are required to achieve similar results.
      CONCLUSIONS: The addition of intensity modulation improves the conformality of
      mMLC-based SCRT. Conformation of dose to the PTV is comparable for IMSRT,
      protons, and IMPT. Concerning the sparing of OAR, IMSRT is equivalent to IMPT,
      and IMPT is superior to conventional protons. The advantage of protons lies in
      the lower integral dose.

PMID- 15519806
TI  - Development of methods for beam angle optimization for IMRT using an accelerated
      exhaustive search strategy.
AB  - PURPOSE: The purpose of this article is to explore the use of the accelerated
      exhaustive search strategy for developing and validating methods for optimizing
      beam orientations for intensity-modulated radiation therapy (IMRT). Combining
      beam-angle optimization (BAO) with intensity distribution optimization is
      expected to improve the quality of IMRT treatment plans. However, BAO is one of
      the most difficult problems to solve adequately because of the huge hyperspace of
      possible beam configurations (e.g., selecting 7 of 36 uniformly spaced coplanar
      beams would require the intercomparison of 8,347,680 IMRT plans). METHODS AND
      MATERIALS: An "influence vector" (IV) approximation technique for high-speed
      estimation of IMRT dose distributions was used in combination with a fast
      gradient search algorithm (Newton's method) for IMRT optimization. In the IV
      approximation, it is assumed that the change in intensity of a ray (or bixel)
      proportionately changes dose along the ray. Evidence is presented that the IV
      approximation is valid for BAO. The scatter contribution at points away from the
      ray is accounted for fully in IMRT optimization after the optimum beam
      orientation has been determined. IVs for all candidate beam angles are generated
      before the start of optimization. For all subsets of beams selected from a given
      pool of beams (e.g., 5 of 24 uniformly spaced beams), the distribution of
      planning scores for the best and the worst plans, optimum angle distributions,
      dose distributions, and dose-volume histograms (DVH) were analyzed for one
      prostate and two lung cancer cases. The results of the exhaustive search
      technique were used to develop a "multiresolution" search strategy. In this
      approach, a smaller number of beams (e.g., three) is first used to explore the
      hyperspace of solutions to determine the most preferred and the least preferred
      directions. The results of such exploration are then used as a starting point for
      determining an optimum configuration comprising a larger number of beams (e.g.,
      seven). This two-step process is considerably faster than full exhaustive search.
      The question to be answered was whether the two methods lead to the same or
      similar solutions. The results of exhaustive search and multiresolution
      approaches were also compared with a previously published approach that used
      beam's-eye-view dosimetrics (BEVD). RESULTS: The relative ranks of plans
      optimized by an accurate dose calculation method were highly correlated with
      those of the plans optimized by the fast calculation method (i.e., using the IV
      approximation), which suggests that an approximate dose calculation algorithm can
      be used effectively for ranking of plans during BAO. We found that dose
      distributions and DVH of many beam configurations within a specified subset from
      a given pool of beams (e.g., 5 of 18) may be clinically indistinguishable and
      acceptable. Their optimized IMRT scores fall in a narrow range, although beam
      configurations and dose distributions may be different. We used the frequency
      distributions as a function of beam angles for the best 100 and the worst 100
      plans to determine the most and the least preferred beam angles. We found that
      the most and the least preferred angle distributions for 3 of 18 configurations
      were very similar to those for 5, 6, 7, or 8 of 18 or 24 configurations, but the
      size of the search space was much smaller for the 3 of 18 case. Using fewer than
      three beams was discovered to be inadequate. This information was used to select
      the most preferred angles and eliminate the least preferred ones before searching
      for the optimum angles for the remaining beams. For the cases we studies, the
      multiresolution strategy produced very similar results to the full exhaustive
      search. Based on the observation that the worst plans had at least one parallel
      opposed pair of beams and virtually all of the best plans had none, we were able
      to further reduce the size of the search space dramatically by using a pool of
      only nonparallel-opposed equispaced beams (i.e., 7 of 19 instead of 7 of 36).
      Another observation was that the probability of finding an optimum configuration
      in a smaller beam pool is substantially lower than in a larger pool (e.g., 5 of
      18 vs. 5 of 24). The implication of this BAO is not very important when a large
      number of beams (nine or more) is used and vice versa. Our results showed that
      the plans with fewer but optimally placed beams could be as good as or better
      than plans using a larger number of unoptimized or uniformly placed beams.
      CONCLUSION: Exhaustive search with fast IMRT algorithms provides a novel and
      realistic approach to study the characteristics of IMRT dose distributions as a
      function of beam angles and to design practical BAO strategies for IMRT planning.

PMID- 15519808
TI  - Plantar fasciitis and the need for translational clarification: in regard to
      Micke et al. (Int J Radiat Oncol Biol Phys 2004;58: 828-843).

PMID- 15519809
TI  - Adjuvant neck dissection after concurrent chemoradiation for advanced head-and
      neck cancer: in regard to Brizel et al. (Int J Radiat Oncol Biol Phys 2004;58:
      1418-1423).

PMID- 15519811
TI  - Determination of TGF-beta1 plasma levels: In regard to Anscher et al. (Int J
      Radiat Oncol Biol Phys 2003;56: 988-995) and de Jaeger et al (Int J Radiat Oncol
      Biol Phys 2004;58: 1378-1387).

PMID- 15519814
TI  - An overview of infection control strategies for equine facilities, with an
      emphasis on veterinary hospitals.
AB  - Infection control entails preventing or minimizing exposure to infectious agents
      or optimizing resistance to infection at the individual and population levels
      should exposure occur. The degree to which each of these strategies is applied
      varies according to the attributes of the disease agent and the population at
      risk. In developing an infection control, biosecurity, or biocontainment plan, it
      is important to decide which agent or agents are to be controlled, the method by
      which they might be introduced to the individual or population, and methods by
      which they might spread once at a farm or veterinary clinic.

PMID- 15519815
TI  - Evolution of equine infection control programs.
AB  - The science of control of infectious diseases in hospitals was born in 1847 when
      Semmelweis, a physician, ordered his medical students to scrub their hands in
      chlorinated lime water between patients and demonstrated that this simple
      procedure resulted ina dramatic decline in patient morbidity and mortality. In
      the late nineteenth century came huge breakthroughs in the understanding that
      microorganisms cause many disorders, and methods to eliminate and control these
      microorganisms were attempted. By 1910, sterile instruments, gowns, masks, and
      gloves had become standard for surgical procedures in large university human
      hospitals, and isolation of human and veterinary patients with contagious
      diseases became standard. With the advent of vaccines, many epidemic viral
      diseases could be controlled, and antimicrobial drugs allowed many previously
      devastating bacterial diseases to be treated effectively. Before long, however,
      bacterial resistance became an important issue and remains so today, particularly
      for Salmonella and Staphylococcus aureus in horses. Vaccination has decreased the
      number of animals susceptible to equine influenza and equine herpesvirus 1, yet
      these contagious diseases still pose a serious issue in large equine veterinary
      hospitals. The development of equine isolation facilities and improved methods of
      barn cleaning; mandatory application of procedures, such as handwashing or use of
      disinfectant hand wipes, to prevent the spread of infectious diseases; and
      monitoring of antimicrobial resistance and use of restricted antimicrobial drugs
      were driven by recognition and necessity and have given rise to current equine
      infection control programs.

PMID- 15519816
TI  - Environmental disinfection to control equine infectious diseases.
AB  - Cleaning and disinfection are essential to the environmental control of
      infectious diseases of all animals. By understanding the types of pathogens,
      environment, and disinfection process, success can be attained in effectively
      stopping disease outbreaks.

PMID- 15519817
TI  - Barrier precautions, isolation protocols, and personal hygiene in veterinary
      hospitals.
AB  - Because nosocomial and zoonotic diseases are inherent and ever-present risks in
      veterinary hospitals, proactive policies should be in place to reduce the risk of
      sporadic cases and outbreaks. Policies should ideally be put in place before
      disease issues arise, and policies should be effectively conveyed to all relevant
      personnel. Written policies are required for practical and liability reasons and
      should be reviewed regularly. Although no infection control program can eliminate
      disease concerns, proper implementation of barrier precautions and isolation can
      reduce the exposure of hospitalized animals and hospital personnel to infectious
      agents. Appropriate personal hygiene, particularly hand hygiene, can assist in
      the prevention of disease transmission when pathogens bypass barriers and are
      able to contact personnel. Veterinary hospitals have moral, professional, and
      legal requirements to provide a safe workplace and to reduce the risks to
      hospitalized patients. Based on experience in the human medical field and on the
      continual emergence of new infectious diseases, infection control challenges can
      only be expected to increase in the future. Regular reassessment of protocols
      based on ongoing research and clinical experiences is required.

PMID- 15519818
TI  - Surveillance for nosocomial infections in veterinary hospitals.
AB  - Surveillance for nosocomial infection and disease is a critical component in an
      integrated and highly effective infection control program. Surveillance
      activities provide a sensory role to guide ongoing control practices so that they
      are focused and efficient. Without input from surveillance results, infection
      control practices are likely to be guided more by emotion and opinion than by
      data and evidence. This article discusses issues to be considered when developing
      effective nosocomial infection surveillance programs as well as the historical
      perspective of surveillance efforts for nosocomial infection in human health care
      settings.

PMID- 15519819
TI  - Salmonella culture: sampling procedures and laboratory techniques.
AB  - In some respects, the multitude of options for isolation of Salmonella and the
      lack of interlaboratory consistency make Salmonella isolation one of the most
      variable procedures in veterinary laboratories. Even with the vast number of
      techniques available, it seems that at least one or two new media become
      available every year that promise to be more sensitive, more specific,and more
      rapid. With all the potential media and techniques available, the diagnostic
      laboratory must choose those that efficiently and accurately give the timely
      results required clinically and epidemiologically. Many veterinary diagnostic
      laboratories have invested the time and effort to explore these options and
      usually have developed standard methods to ensure that their laboratory tests
      have high sensitivity and specificity. Clients have greater assurance in the
      accuracy of laboratory results if these standards and the process of deriving
      them are made available to them. Many laboratories participate in external
      quality assurance programs to demonstrate their ability to culture microorganisms
      accurately. These quality control programs are designed to ensure that the client
      receives the correct answers to questions that are vital for the treatment and
      health care of their horses. This important information is available only if the
      initial steps of collecting and shipping the samples have been executed
      appropriately.

PMID- 15519820
TI  - Multidrug-resistant Salmonella and nosocomial infections.
AB  - Nosocomial infections are a serious threat to optimum patient care. In addition,
      nosocomial infections can have far-reaching consequences for the hospital
      personnel and the financial aspects of the hospital. Nosocomial infections with
      Salmonella spp have been described among hospitalized equine populations more
      frequently than any other agent. Salmonella spp associated with hospitalized
      equids often possess more antimicrobial resistance determinants than do
      Salmonella spp isolated from healthy horses in the general population. There is
      little evidence to suggest that resistant salmonellae are more virulent than
      nonresistant forms. MDR forms of Salmonella complicate the selection of
      appropriate antimicrobials when they are indicated, however. Furthermore, the use
      of some antimicrobials may apply selection pressure toward enhanced ability of
      MDR Salmonella to colonize equine patients. Further research should help to
      elucidate the risky uses of antimicrobials in the hospital setting and define the
      role of disinfectants and treatments such as NSAIDs in the ecology of MDR forms
      of nosocomial infections, including Salmonella. In the meantime, thoughtful
      selection of when and how to use antimicrobials in equine patients, together with
      deliberate selection of which antimicrobials to use based on monitoring data and
      other factors, such as safety and spectrum, is advised.

PMID- 15519821
TI  - Methicillin-resistant Staphylococcus aureus in horses and horse personnel.
AB  - Fortunately, MRSA infection and colonization are currently uncommon in veterinary
      medicine. Nevertheless, the increasing reports of the occurrence of MRSA
      infection in horses, veterinarians, and equine personnel dictate that serious
      consideration be given to the control of this pathogen in veterinary hospitals as
      well as in the equine community. It is unclear whether extrapolation from human
      hospitals and people in the community is appropriate; however, given the rapid
      increase in nosocomial MRSA in human hospitals and the recent shift of certain
      clones of MRSA into the community, it would be unwise to ignore this potential
      pathogen. If equine MRSA did, indeed, originate in the human population, complete
      eradication in the equine population is unlikely, regardless of the prevalence of
      infection in horses and the intensity of infection control measures, without
      concurrent eradication of MRSA in the human population, which is surely an
      impossible feat. Early institution of appropriate surveillance and other
      infection control measures should be used to attempt to limit the impact of MRSA
      in veterinary medicine, however. It has been stated, "The time to act is now,
      before the prevalence of MRSA in the community begins to rise and we end up with
      50% of the community strains becoming methicillin-resistant". This statement was
      directed at control of MRSA in people; however, it is equally relevant in the
      veterinary context and should receive strong consideration.

PMID- 15519822
TI  - Clostridium difficile diarrhea: infection control in horses.
AB  - C difficile has emerged as an important cause of diarrheic disease in horses. C
      difficile diarrhea is usually diagnosed in mature horses, mostly when they are
      treated with antimicrobials and hospitalized. It is important for clinicians at
      veterinary hospitals to have knowledge about the organism and the infection. To
      prevent C difficile diarrhea, judicious use of antimicrobials is important, as is
      minimizing different stress factors at the animal hospital or clinic. Infected
      horses must be isolated. Routine examination for C difficile and toxin A or B is
      recommended in horses with antibiotic-associated diarrhea. When treating foals
      for R equi pneumonia, it is important to avoid accidental ingestion of
      erythromycin by the dams. To reduce the number of environmental spores, thorough
      cleaning and surface disinfection of the animal hospital and clinic are
      important. Routine handwashing should be performed by all staff.

PMID- 15519823
TI  - Equine herpesvirus 1 and 4.
AB  - Equine herpesvirus infections in horses remain a significant cause of abortion
      and neurologic disease. These viruses are also responsible for mild signs of
      respiratory disease. The ability to establish latent infections with periodic
      reactivation or transmission to other horses is an important feature of these
      herpesviruses. One of the most unique aspects of this report is the description
      of horses demonstrating neurologic signs serving as the source of infection for
      other horses. Accurate diagnosis and better means of protection for horses remain
      problems facing veterinarians and horse owners.

PMID- 15519824
TI  - Horses and the risk of zoonotic infections.
AB  - Infectious agents are insidious, often changing to adapt to host defenses or
      treatment advances. Because these challenges will continue, the need to apply
      standard and transmission-based precautions is important not only in the human
      hospital setting but in the veterinary clinic setting. In addition, to prevent
      human infection and potential liability, clinics need to establish program
      algorithms to prevent disease spread for specific agents or planned procedures to
      respond to potential nosocomial and zoonotic disease events. These need to be
      done proactively. Furthermore, more money needs to be dedicated to establish
      infection control programs and to improve the science of infection control in the
      veterinary setting.

PMID- 15519825
TI  - [Extreme prematurity: optimism or pessimism].

PMID- 15519826
TI  - [Consequences for the family of a very preterm birth two months after discharge.
      Results of the EPIPAGE qualitative study].
AB  - OBJECTIVES: To assess mothers' and fathers' psychological health 2 months after
      discharge of a very preterm infant. To describe the problems encountered with the
      child, the quality of the marital relationship, the organization of the family
      and to compare the answers made by mothers and fathers. POPULATION: Mothers
      having delivered before 33 weeks in two maternity units in Paris and in Rouen
      were contacted. Among the 38 mothers who were eligible, 21 accepted to
      participate. Their children were born between 26 weeks and 32 weeks and weighted
      from 630 to 2100 g. METHOD: A semi-structured interview was conducted at home by
      a psychologist with each member of the couple. It lasted approximately 1 h. Each
      interview was tape-recorded and fully transcribed. The analysis allowed to
      discover the main themes emerging from the interviews and to search for the role
      of factors. RESULTS: Two months after discharge, mothers expressed anxiety and
      feelings of depression. Fathers noted considerable fatigue and both parents
      expressed concerns about the child's health and development. Marital
      dissatisfaction and behavioural symptoms in siblings were also noted. Mothers'
      difficulties were not linked to the degree of prematurity or length of stay in
      neonatal unit but with the baby's present health state, his rehospitalizations
      and maternal characteristics such as isolation, lack of support and previous
      perinatal loss. The mother's psychological organisation modifies the role of
      objective factors. Fathers seemed more able to cope with and overcome the
      traumatic event caused by the very preterm birth. They insisted on their role of
      support for the mother and the mother-child relationship. CONCLUSION: The
      consequences of a very preterm birth are important and concern the whole family.
      After hospital discharge, the follow-up care of the very preterm baby should take
      the family social and psychological situation into account.

PMID- 15519827
TI  - [Use of diazepam in the treatment of opioid neonatal abstinence syndrome].
AB  - INTRODUCTION: The fetal opiate exposure presents many risks for the newborn. One
      of the most important is the neonatal abstinence syndrome that associates
      neurological and digestive signs. In some cases the vital prognosis can be
      involved. The evaluation of the syndrome's severity is based on certificated
      scales. The mortality has been reduced by the improved management of these
      neonates. Diamorphine, phenobarbital, chlorpromazine and diazepam are the most
      currently used. However, there is no consensus on the treatment. The data
      concerning the treatment are controversial, especially for the use of diazepam.
      The aim of our study was to describe the effects of diazepam obtained in three
      different centers and to compare our results to those of the literature.
      POPULATION AND METHODS: Twenty-three neonates were included. They were all
      hospitalized for abstinence syndrome and treated by diazepam. The Finnegan scale
      was used to evaluate the symptom's severity and the effects of the diazepam. The
      principal evaluation criteria were the duration of treatment and hospitalization,
      the timing in recovery of birth weight and the percentage of birth weight loss.
      RESULTS: The average treatment duration was 7 days, the average hospitalization
      duration was 18 days, the birth weight was recovered at 10 days of life and the
      percentage of loss of birth weight was 6.5%. Diazepam treatment failed in only
      one case. No case of intense dehydration occurred. CONCLUSION: Due to the
      retrospective design of the study, the diazepam could not be compared to other
      drugs. Nevertheless, it argues against the "anti-diazepam" attitude. A controlled
      randomised prospective study is needed to evaluated the optimal therapeutic
      strategy.

PMID- 15519828
TI  - [A routine prospective survey process to detect nosocomial bacterial colonization
      in a neonatal unit: risk factors for acquisition].
AB  - A systematic analysis of weekly nasal and rectal swabs was carried out in a
      neonatal unit in order to detect colonization with multiresistant bacteria (MRB).
      PATIENTS AND METHODS: During a 6-month period, rectal and nasal samples were
      taken in 187 consecutively hospitalized newborns, the day of the admission (day
      0) and every week until discharge, in order to detect MRB, mainly methicillin
      resistant coagulase negative staphylococci (MRCoNS), Staphylococcus aureus and
      multi-resistant Gram-negative bacilli. RESULTS: Among 187 infants, 50 were
      already colonized at entrance and excluded from the study. In others, 49 (35%)
      were colonized by at least one MRB, with a total of 71 strains isolated. The most
      frequent was MRCoNS, especially Staphylococcus epidermidis (66.1%). Gram-negative
      bacilli accounted for 9.8%. Colonization began earlier with MRCoNS than with Gram
      negative bacilli, 7.8 +/- 6 vs. 15.5 +/- 16 days, P=0.004, and finished earlier
      22.7 +/- 15 vs. 38.5 +/- 16 days, P=0.03. Colonized children exhibited by
      univariate analysis a lower birth weight, more frequent parenteral nutrition or
      previous hospitalization in a neonatal unit and a younger age at admission. Odds
      ratio for colonization were 4.06 for prematurity and 43.83 for a previous
      hospitalization. MRCoNS at days 15 (P <0.05) and 22 (P <0.05) were correlated
      with the empiric use of antibiotics. No nosocomial infection occurred during the
      study. CONCLUSION: A high rate of newborns were colonized with MRB in our unit,
      especially MRCoNS, acquired earlier than Gram-negative bacilli, with a favoring
      action of empiric antibiotherapy.

PMID- 15519829
TI  - [Prolonged fever in children. Retrospective study of 67 cases].
AB  - BACKGROUND: The first problem to face in prolonged fever is its etiologic
      diagnosis. Its incidence varies between 0,5 to 3% of all paediatric hospital
      stay. Precise diagnosis need an extensive questionnary, complete physical
      examination and an algorithm of complementary exams. PURPOSE: To precise the
      epidemiologic profile and causes of prolonged fever in a children. POPULATION AND
      METHODS: Retrospective review of 67 children between two and 15 years old
      admitted in the general paediatrics department of the Fattouma Bourguiba
      university hospital in Monastir (Tunisia), for prolonged fever between 1(st)
      January 1988 and 31 December 1998. RESULTS: The incidence of prolonged fever was
      1,02%. The mean age was seven years with female predominance. The mean fever
      duration was 30 days. Fever was isolated in 23,9% of cases. Fever was associated
      to rheumatic or respiratory signs in respectively 26,9% and 20,9% of cases.
      Hospital-stay was of 11 days in 50% of cases. Prominent causes were dominated by
      infectious diseases (56,7%) with predominance of localized infections, followed
      by inflammatory diseases (20,9%) with predominance of rheumatic fever and
      neoplasms (3%). Fever remained of unknown origin was seen in 19,4% of cases.
      CONCLUSION: Prolonged fever is still dominated by infectious and inflammatory
      diseases and depend on local epidemiological particularities. In fact we noted in
      this study the relative high-frequency of visceral leishmaniasis, complicated
      pulmonary hydatic cyst and rheumatic fever. The diagnosis approach should be
      based on complementary exams of first and second stage because of their high
      number and cost. Prognosis of fever of unknown origin is often favorable.

PMID- 15519830
TI  - [Thyroid dysfunction after haematopoietic stem cell transplantation during
      childhood].
AB  - To evaluate the percentage and risk factors of thyroid dysfunction in 79 children
      who underwent bone marrow transplantation in a single centre. PATIENTS AND
      METHODS: The mean age of the cohort was 6.8 and mean follow-up 5.5 years. The 79
      patients were divided in two groups according to the pretransplant conditioning
      regimen: fractionated total body irradiation (TBI)(N=54), chemotherapy with
      Busulphan (N=25). Thyroid function was evaluated by thyroid-stimulating hormone
      (TSH) and free thyroxine (fT4) tests. Overt hypothyroidism was defined by low fT4
      blood levels and TSH > 4 mU/l, and compensated hypothyroidism by normal fT4 index
      and TSH >4 mU/L. RESULTS: The six-year probability of hypothyroidism was 36 +/-6%
      for the whole group of 79 patients, 49 +/-8% after TBI and 9 +/-6% in the
      Busulphan group (P <0.001). Neither gender, nor primary disease, nor presence of
      graft versus host disease were found to be statistically significant for
      occurrence of hypothyroidism in the TBI group. However, a younger age seemed to
      influence statistically the 6-year probability of hypothyroidism in the TBI
      group: 59 +/-9% if age <7.7 years versus 34 +/-13% if age >7.7 years (P =0.02).
      CONCLUSION: A careful follow-up of thyroid function is recommended even without
      TBI conditioning regimen. Young age as a potential risk factor of hypothyroidism
      has never been described and needs to be studied in a larger cohort.

PMID- 15519831
TI  - [Honey bees massive poisoning in an infant].
AB  - The authors report the case of an infant who survived a massive poisoning of
      honey bees (>350 bees stings) in 2002. The infant presented convulsions, anaemia,
      renal failure and haematuria. The main treatment consisted in administration of
      adrenaline. Systematic and early administration of this drug has limited the
      severe clinical picture despite massive attack.

PMID- 15519832
TI  - [Hereditary neuralgic amyotrophy: a paediatric and familial presentation of
      Parsonage-Turner syndrome].
AB  - Hereditary neuralgic amyotrophy is a rare disorder, characterized by recurrent
      attacks of pain in a brachial plexus distribution. We report the case of a 12
      year-old boy with several attacks of pain and atrophy of the muscles of the
      shoulders. The age of onset of this disease is variable, most frequently in the
      second or third decade. Pediatric onsets, during the first decade are rare. The
      differences between the hereditary neuralgic amyotrophy and the sporadic
      Parsonage-Turner syndrome are painful recurrent episodes of weakness and similar
      familial cases. The analysis of several families has shown that hereditary
      neuralgic amyotrophy phenotype is heterogeneous and two different clinical
      courses can be discerned. Recent evidence indicates that HNA is genetically
      heterogeneous. Pathophysiology of the disease remains unclear, so the treatment
      is not clearly established.

PMID- 15519833
TI  - [Gluthathion synthetase deficit in a newborn infant].
AB  - CASE REPORT: We report an observation of a triplet newborn presenting with
      haemolysis, metabolic acidosis with no lactic acidosis revealing a glutathione
      synthetase deficiency. These biological signs were associated with multiple
      malformations (IUGR, toes hypoplasia and cerebral ventricular anomalies), not
      described in this disease. CONCLUSION: This rare diagnosis can be confirmed by
      elevation of urinary 5-oxoproline. Prognosis is linked to diagnosis and treatment
      precocity. We have no argument to think that the malformations we found are
      related to a glutathione synthetase deficiency. However, as the neurological
      evolution is often unfavourable, neuroradiological explorations could give
      information about the location and severity of potential cerebral lesions.

PMID- 15519834
TI  - [Patent omphalomesenteric duct (a case report)].
AB  - PURPOSE: To report a rare case of patent omphalo-mesenteric duct and discuss the
      pathogenesis, clinical and radiological findings of this pathology. CASE REPORT:
      A two-month-old infant presented with umbilical liquid production since birth.
      Local examination showed an inflammatory umbilical tumefaction. Catheterization
      and injection of contrast material through the canal evidenced a communication
      with the gut, consistent with a patent omphalo-mesenteric duct. DISCUSSION:
      Persistent omphalo-mesenteric duct is a rare affection. Diagnostis is based on
      clinical and radiological findings. Clinical findings may be atypical in some
      cases. Complications are severe and include prolapsus, occlusion, ulcus,
      haemorrhage and perforation. CONCLUSION: Diagnostis of patent omphalo-mesenteric
      duct must be precocious to avoid complications.

PMID- 15519835
TI  - [Secondary surfactant deficiencies in extremely low birth weight premature
      infants].
AB  - Primary deficiency of surfactant is responsible for the respiratory distress
      syndrome and concerns premature neonates born before 33 weeks of gestation.
      However, newborns may develop respiratory disorders related to a secondary
      deficiency or dysfunction of surfactant. We report the course of three extremely
      low birth weight premature infants who experienced clinical respiratory
      decompensation at two weeks and showed a marked improvement after exogenous
      natural surfactant administration.

PMID- 15519836
TI  - [Secondary surfactant deficiencies].
AB  - Preterm babies born before the 33rd week of gestation often exhibit primary
      surfactant deficiency responsible for the respiratory distress syndrome or
      hyaline membrane disease. In that situation, there is a limited and insufficient
      production of surfactant by type II alveolar cells of the lung due to immaturity.
      Secondary surfactant deficiencies occur in patients with prior normal surfactant
      synthesis and can be related to sepsis, hypoxia, ventilator induced lung injury
      or surfactant inhibition by a variety of substances reaching the alveolar spaces.
      They occur in full-term newborns with meconium aspiration syndrome, acute
      respiratory distress syndrome and congenital diaphragmatic hernia. In children
      and adults, acute respiratory distress syndrome and respiratory syncytial virus
      bronchiolitis can be responsible. In prematures they occur after the initial
      primary deficiency during pulmonary hemorrhage, pneumonia and bronchopulmonary
      dysplasia. Treatment with exogenous surfactant may be beneficial. There is a need
      for randomized controlled studies for evaluation of this treatment. Next
      generation of surfactants containing recombinant surfactant protein or synthetic
      peptides appear as promising agents in these situations of secondary surfactant
      deficiencies.

PMID- 15519837
TI  - [Vaccination against hepatitis A in children].
AB  - Hepatitis A is usually considered as a mild disease and is asymptomatic in more
      than 80% of children less than 5 years of age. Furthermore, incidence of the
      disease decreased dramatically in France during the past decades. For these
      reasons mass routine vaccination is not required in our country. However,
      infected children shed the virus in the community and are responsible for
      secondary cases, sometimes severe. That is why, despite the cost and the absence
      of reimbursement of the vaccine, immunisation against hepatitis A is recommended
      in children attending health-care institutions, in children with chronic liver
      disease and in those travelling in endemic areas. Prophylaxis around an index
      case is the main problem because non-specific immunoglobulins, although
      recommended, are not available in France for this indication. Vaccination in the
      few days following exposition has been reported to be efficient in household
      contacts and small communities, including nurseries. This strategy is recommended
      by the British Advisory Board within the 7 days following exposition, but not in
      France. However, it can be proposed to the family by paediatricians.

PMID- 15519839
TI  - [Are IgE-independent food hypersensitivity and functional constipation in
      children related?].

PMID- 15519838
TI  - [Immunity, infections, and nutritional status of HIV-positive children in the
      pediatric's ward UHC of Treichville in Ivory Coast].

PMID- 15519840
TI  - [Inhaled treatment for asthma in practice].
AB  - The modalities of an inhaled treatment depends on the characteristics of the
      aerosol, on the age of the child, and mainly on the inhalatory system. Before the
      age of 8 years, the pressurised metered dose inhaler must be used together with a
      spacer device. Above this age, the use of a breath-actuated inhaler or of a dry
      powder inhaler can be proposed. Demonstration and educational instructions will
      increase the probability of compliance and efficiency of the treatment.

PMID- 15519841
TI  - [Management of acute visual loss in children].
AB  - Acute or rapidly progressive visual loss in children needs urgent attention and
      treatment. It may be unilateral orbilateral. Etiology depends upon the involved
      areas: eye ball, optic nerve, retro-chiasmatic pathways. Psychogenic origin is
      quite common in school-age children, however, it has to be considered last.
      Unilateral visual loss may be overlooked. Acute total transitory visual loss may
      be due to epilepsy or to migraine. Rapidly progressive visual loss may be due to
      retinal disease, optic neuritis or cortical blindness. Management of visual loss
      depends on clinical features, associated symptoms, and aspect of the optic disc.
      It needs collaboration between ophthalmologist,pediatrician and
      neuropediatrician. Retinal hemorrhages first call to mind a traumatic origin.
      Swelling of the optic disc may be due to increased intracranial pressure or due
      to optic neuritis. When the optic disc is normal it is necessary to rule out
      organic diseases before establishing the diagnosis of a psychogenic vision
      disturbance. In emergency, brain neuroimaging is the best way to diagnose
      intracranial mass and visualize optic pathways.

PMID- 15519842
TI  - [Headache in childhood: which diagnostic imaging strategies?].
AB  - There are various causes of headaches in children. The majority of cases are
      considered as primary and include migraine and tension headaches. Headaches
      secondary to an underlying pathology are much less frequent. The aim of imaging
      will be to depict lesions that can benefit from specific therapy and hence
      improve life quality and expectancy of the affected child. In case of secondary
      headaches, imaging will have to precise the diagnosis, which is based mainly upon
      history of the disease and clinical findings. These findings are important to the
      radiologist as they will help to choose the more adequate technique between CT
      scan and MRI. This choice is based upon the presumed diagnoses, degree of
      emergency and availability of the technique. Knowledge of the differential
      diagnoses influences the way to perform the examination itself (choice of slice
      thickness, plane of imaging, MR sequences, need for an MR angiogram or injection
      of contrast medium...). In our opinion, dedicated MR imaging is the technique of
      choice to investigate secondary headaches in children given its superior
      sensitivity in depicting certain tumors (glioma of the pons, posterior fossa
      tumors...), intracranial hypotension, Chiari I malformation, lesions of the
      hypothalamo-hypophyseal axis etc...

PMID- 15519843
TI  - [Asthma among elite athletes].
AB  - The prevalence of asthma and exercise induced asthma increase in elite athletes
      of national and international level especially in endurance sports. Prolonged
      hyperventilation of dry or cold air and increased inhalation of pollutants or
      allergens could be an explanation. The subsequent airway inflammation which seems
      to regress in subjects quitting competition differs from classical asthma. This
      could represent a chronic adaptive response to exercise hyperventilation. With a
      proper treatment, asthma and exercise induced asthma are not a limiting factor
      for sport results, but the short and long term effects of exercise on intensive
      training athletes need further study. Moreover, a specific follow-up is needed in
      all individuals, asthmatic or not, training intensively.

PMID- 15519844
TI  - [Use of palivizumab for the prevention of respiratory syncytial virus infections
      in children with congenital heart disease. Recommendations from the French
      Paediatric Cardiac Society].
AB  - Palivizumab is now authorized in France for prophylaxis of respiratory syncytial
      virus (RSV) infections in infants with haemodynamically significant congenital
      cardiac disease. A multicentre randomised trial was shown that treatment was safe
      and effective for such children. The therapeutic protocol is similar to that used
      in preterm infants and consists of five, monthly, intramuscular injections of
      palivizumab, at a dose of 15 mg/kg, started 2 months before the onset of epidemic
      season. To guide clinicians to identify children most likely to benefit from
      prophylaxis, the Pediatric Cardiac Group of French Cardiac Society has proposed
      recommendations. Prophylaxis with palivizumab is recommended in high-risk infants
      for respiratory complications after RSV infection: infants under I year old; left
      to right shunt with cardiac failure, failure to thrive, pulmonary hypertension or
      bronchial compression; cyanotic heart disease with oxygen saturation lower than
      0.8 at rest; congenital cardiac disease expected to need admission for surgery or
      catheterization during the epidemic season; cardiomyopathy with cardiac failure;
      primary or secondary pulmonary hypertension; symptomatic children aged over I
      year with complex cardiac disease. Decisions regarding prophylaxis with
      palivizumab should be made in collaboration with the pediatric cardiologist in
      order to optimize the cost-benefice ratio, on the basis of the degree of
      physiologic cardiovascular compromise.

PMID- 15519845
TI  - [Hyperactivity in infants below the age of six].
AB  - "Attention deficit with hyperactivity disorder" is a syndrome very difficult to
      detect at the earlier age of the life,before 3 or 4 years. Early signs are
      aspecific and the impact of the syndrome on socio-scolar adaptation is only
      detectable later on. So, the proto-syndrome is still discussed. It seems really
      important to face this problem in a polyfactorial perspective and in the light of
      child's history, because the signification and the meaning of the troubles are
      the key of the therapeutical choice which is not reducible only to amphetamine
      like treatment.

PMID- 15519846
TI  - Magic touch: how does cell-cell adhesion trigger actin assembly?
AB  - The formation of cadherin-mediated cell-cell junctions is accompanied by a
      profound remodeling of the actin cytoskeleton. The Arp2/3 complex and its
      activator cortactin drive the assembly of branching actin-filament arrays, and
      formin-1 promotes the nucleation of non-branching actin filaments. Recruitment of
      these actin nucleators to nascent adhesions, formation of the links between them
      and the cytoplasmic cadherin domain, and triggering of their actin-polymerizing
      functions are vital steps in the development of cell-cell junctions. In this
      article, I discuss recent results showing that proteins involved in the
      regulation of actin polymerization have crucial roles in the development and
      maintenance of the cadherin junctions.

PMID- 15519847
TI  - An enemy within: fly reconnaissance deploys an endonuclease to destroy nonsense
      containing mRNA.
AB  - Quality-control mechanisms function in cells to ensure proper gene expression.
      Nonsense-mediated mRNA decay (NMD) is one such mechanism and it degrades abnormal
      mRNAs that contain a premature-termination codon. Although NMD is conserved in
      all eukaryotes that have been examined, it can manifest mechanistic differences
      in different organisms. A recent study using Drosophila melanogaster describes a
      new mechanistic twist to NMD.

PMID- 15519848
TI  - Mechanism of the eukaryotic chaperonin: protein folding in the chamber of
      secrets.
AB  - Chaperonins are key components of the cellular chaperone machinery. These large,
      cylindrical complexes contain a central cavity that binds to unfolded
      polypeptides and sequesters them from the cellular environment. Substrate folding
      then occurs in this central cavity in an ATP-dependent manner. The eukaryotic
      chaperonin TCP-1 ring complex (TRiC, also called CCT) is indispensable for cell
      survival because the folding of an essential subset of cytosolic proteins
      requires TRiC, and this function cannot be substituted by other chaperones. This
      specificity indicates that TRiC has evolved structural and mechanistic features
      that distinguish it from other chaperones. Although knowledge of this unique
      complex is in its infancy, we review recent advances that open the way to
      understanding the secrets of its folding chamber.

PMID- 15519849
TI  - Plant and animal stem cells: conceptually similar, molecularly distinct?
AB  - Animals and plants maintain small pools of stem cells that continuously provide
      the precursors of more-specialized cells to sustain growth or to replace tissues.
      A comparison of plant and animal stem cells can highlight core aspects of stem
      cell biology. In both types of organism, stem cells are maintained by
      intercellular signals that are available only in defined regions (niches) in the
      tissues. Although plants use different signals and are more flexible at
      establishing stem-cell niches in new locations, recent evidence suggests that the
      mechanisms restricting cell fate in stem-cell progeny are similar in both
      kingdoms and might pre-date the evolution of multicellular organisms.

PMID- 15519850
TI  - Of rings and levers: the dynein motor comes of age.
AB  - After nearly four decades of investigation, the dynein motor is finally on the
      verge of revealing its inner secrets. This multisubunit ATPase participates in
      several important microtubule-based motilities in eukaryotic cells. Numerous
      recent articles have advanced the understanding of the dynein motor substructure
      and its mechanism of force production, revealing both similarities to other
      motors and some surprises. We are now in a position to summarize a basic
      blueprint for dynein. At its core, the motor is a ring-shaped object with two
      protruding levers: one engages cargo and might provide much of the force for
      movement, and the other interacts with the microtubule track. The activities of
      both levers are linked through nucleotide-dependent conformational changes in the
      ring.

PMID- 15519851
TI  - Gastrulation dynamics: cells move into focus.
AB  - During vertebrate gastrulation, a relatively limited number of blastodermal cells
      undergoes a stereotypical set of cellular movements that leads to formation of
      the three germ layers: ectoderm, mesoderm and endoderm. Gastrulation, therefore,
      provides a unique developmental system in which to study cell movements in vivo
      in a fairly simple cellular context. Recent advances have been made in
      elucidating the cellular and molecular mechanisms that underlie cell movements
      during zebrafish gastrulation. These findings can be compared with observations
      made in other model systems to identify potential general mechanisms of cell
      migration during development.

PMID- 15519852
TI  - CSF-1 regulation of the wandering macrophage: complexity in action.
AB  - Most tissue macrophages and osteoclasts are regulated by colony-stimulating
      factor-1 (CSF-1, also known as macrophage CSF). The effects of CSF-1 are mediated
      by the CSF-1 receptor tyrosine kinase (CSF-1R), through autophosphorylation of
      CSF-1R and the subsequent phosphorylation of downstream molecules. Triggering
      this phosphorylation cascade increases gene transcription and protein
      translation, and induces cytoskeletal remodeling by several signaling pathways,
      leading to the survival, proliferation and differentiation of target cells. CSF-1
      regulated tissue macrophages are important for innate immunity and for tissue
      development and function. Because CSF-1 regulates the survival, proliferation and
      chemotaxis of macrophages and supports their activation, this factor is involved
      in the pathogenesis of several diseases.

PMID- 15519853
TI  - Renewing the conspiracy theory debate: does Raf function alone to mediate Ras
      oncogenesis?
AB  - Ras proteins function as signal transducers and are mutationally activated in
      many human cancers. In 1993, Raf was identified as a key downstream effector of
      Ras signaling, and it was believed then that the primary function of Ras was
      simply to facilitate Raf activation. However, the subsequent discovery of other
      proteins that are effectors of Ras function suggested that oncogenic activities
      of Ras are mediated by both Raf-dependent and Raf-independent signaling. Further
      complexity arose with the identification of Ras effectors with putative tumor
      suppressor, rather than oncogenic, functions. However, the recent identification
      of B-raf mutations in human cancers has renewed the debate regarding whether Raf
      activation alone promotes Ras-mediated oncogenesis. In this article, we summarize
      the current knowledge of the contribution of Ras effectors in Ras-mediated
      oncogenesis.

PMID- 15519854
TI  - Bacterial social engagements.
AB  - Quorum sensing is a process that enables bacteria to communicate using secreted
      signaling molecules called autoinducers. This process enables a population of
      bacteria to regulate gene expression collectively and, therefore, control
      behavior on a community-wide scale. Quorum sensing is widespread in the bacterial
      world and, generally, processes controlled by quorum sensing are unproductive
      when undertaken by an individual bacterium but become effective when undertaken
      by the group. Cell-cell communication can occur within and between bacterial
      species, and between bacteria and their eukaryotic hosts, which suggests that the
      chemical lexicon is complex. Prokaryotic and eukaryotic mechanisms for enhancing
      and inhibiting quorum sensing have been identified, which suggests that
      manipulation of quorum-sensing-controlled processes could be common in bacterial
      bacterial and bacterial-eukaryotic associations.

PMID- 15519855
TI  - Targeted therapy for malignant gliomas.
AB  - The identification of markers that are associated with tumour but not normal
      tissue has allowed the development of highly-specific targeted therapies.
      Monoclonal antibodies, either alone or linked to radioisotopes or toxins, have
      provided a powerful tool for research, as well as the basis for promising
      therapeutic agents with less side effects than standard radiotherapy or
      chemotherapy. A new class of drugs, the tyrosine kinase inhibitors, which
      interfere with the function of key molecules in cancer-promoting pathways, have
      had a dramatic effect in haematological malignancy and are being trialled in
      solid tumours, including glioma. Although the problem of achieving specific, high
      level delivery of these various agents to tumours in the brain remains a major
      issue, encouraging early results with some targeted agents support the attractive
      theoretical principles of this new paradigm. Further work to identify new
      molecular targets and to develop agents exploiting them, is needed, as well as
      confirmation of their safety and efficacy by clinical trials.

PMID- 15519856
TI  - Acute complications of dopamine agonist treatment for macroprolactinoma - how
      uncommon?
AB  - Dopamine agonists are first line treatment for prolactinomas. This treatment can
      cause serious complications in patients with invasive macroprolactinomas. This
      study reviewed 195 patients attending the endocrine clinic and/or undergoing
      surgery for pituitary tumours at The Royal Melbourne Hospital in a seven-year
      period (1996-2002). Thirty three patients had macroprolactinoma (diameter >10
      mm). Eleven of them were treated with dopamine agonist prior to surgery and four
      developed severe complications. This study suggests that the severe complications
      of dopamine agonist therapy may be higher than previously reported. All patients
      should be educated about these complications and their early recognition.

PMID- 15519857
TI  - Cost analysis of unilateral and bilateral pallidotomy for Parkinson's disease.
AB  - With the rapid increase in provision of deep brain stimulation for Parkinson's
      disease, the efficacy of pallidotomy in symptom alleviation appears to be
      increasingly ignored. We demonstrate that lesional surgery is effective with
      benefit over a significant period of time with very significant societal cost
      savings. Such studies are essential for future planning of services so that
      maximum numbers of patients can benefit from surgery, both lesional and
      neuromodulation, as deemed appropriate.

PMID- 15519858
TI  - CT scan in minor head injury: a guide for rural doctors.
AB  - Minor head injury in a developing country like Malaysia is managed by primary
      care physicians and/or medical assistants in district hospitals. These patients
      are seen initially in their local hospitals, which have at least an X-ray machine
      for the purpose of screening. This study aimed to guide these physicians to
      manage these patients at a primary care level. A cross-sectional study was
      conducted and the study revealed significant predictors of significant computed
      tomographic (CT) findings. The presence of a Glasgow coma scale (GCS) score of 14
      or 13 was associated with the risk of developing significant CT findings compared
      to patients with a GCS of 15 (p<0.001). Thirty-seven out of 50 patients with GCS
      of 14 or 13 developed clinically significant brain injury on CT scan. Similarly,
      the presence of skull fracture was associated with the risk of developing CT
      abnormalities (p<0.001). Forty-two out of 51 patients with skull fracture
      developed clinically significant CT findings. Vomiting was associated with
      developing CT abnormalities (p=0.017). Twenty-seven out of 40 patients with
      vomiting showed significant CT findings. Soft tissue injury was also found to be
      associated with developing CT abnormalities (p=0.007). Therefore, we propose
      reclassifying minor head injury based on the GCS score. Patients with a GCS score
      of 15 were classified as having mild head injury, while patients with a GCS score
      of 13 or 14 were at higher risk of developing brain injury and therefore
      categorized as high risk mild head injury. This group requires emergency CT scan
      examination, especially when associated with non-motor vehicle accidents,
      abnormal central nervous system (CNS) examination, craniofacial injuries or skull
      fractures. They should be referred to a general surgical unit which can treat
      head injuries or a neurosurgical tertiary centre.

PMID- 15519859
TI  - Surface rendered three-dimensional MR imaging for the evaluation of trigeminal
      neuralgia and hemifacial spasm.
AB  - Surface rendered three-dimensional (SR3D) magnetic resonance (MR) imaging was
      used to visualize the cerebellopontine angle nerves, blood vessels and brain stem
      and compared with the operative view in patients undergoing microvascular
      decompression. Thirty-one patients with 32 affected nerves manifesting as
      trigeminal neuralgia (TN, 16 cases), hemifacial spasm (HFS, 14 cases) and
      glossopharyngeal neuralgia (2 cases) underwent microvascular decompression at the
      Kanto Neurosurgical Hospital between February 2001 and July 2002. Preoperative MR
      imaging and MR angiography were performed in all patients. The SR3D MR image and
      the operative view correlated in 30 of the 31 patients. A very thin artery was
      not detected in one patient with TN. SR3D MR imaging can clearly demonstrate the
      three-dimensional relationship between the nerves and the offending vessel, so is
      very effective for the preoperative planning of microvascular decompression in
      cases of TN and HFS.

PMID- 15519860
TI  - Functional MRI near vascular anomalies: comparison of cavernoma and arteriovenous
      malformation.
AB  - BACKGROUND AND PURPOSE: Mapping of eloquent cortex using blood-oxygen-level
      dependent (BOLD) contrast functional MRI (fMRI) has rapidly gained acceptance as
      part of the evaluation of patients being considered for neurosurgical
      interventions. The BOLD signal measures local susceptibility in the blood, which
      can change during periods of increased neuronal activation as a result of
      alteration in blood flow and cerebral oxygen utilisation. Vascular anomalies
      could influence the BOLD signal via their effects on both blood flow and
      susceptibility. METHODS: In the present study we have compared the fMRI signal
      associated with functional activation near arteriovenous malformations and
      cavernomas in a group of patients referred for pre-surgical mapping of eloquent
      cortex. RESULTS: The magnitude of the BOLD signal was not different for the
      cavernoma group and the AVM group (mean percentage signal change 6.3% vs. 5.5%).
      For subjects with cavernoma, there was an increase in cavernoma volume on the
      functional images compared to T1-weighted anatomical images (mean 570%), and a
      BOLD signal was only detected outside the enlarged cavernoma. CONCLUSION: The
      findings show that susceptibility effects associated with cavernoma, most likely
      due to hemosiderin deposition, can result in an apparent increase in the
      separation between the BOLD signal and the cavernoma itself. This could lead to
      falsely high levels of surgical confidence during neurosurgical resection.
      Differential patterns of blood flow associated with cavernoma and AVM do not
      appear to significantly affect the BOLD signal magnitude.

PMID- 15519861
TI  - Outcome after traumatic frontal intracerebral haemorrhage: a comparison of
      unilateral and bilateral haematomas.
AB  - Frontal intracerebral haemorrhage (ICH) is a common result of cranial trauma.
      Outcome differences between bilateral and unilateral frontal ICH are not well
      studied but would be valuable to predict prognosis in clinical practice. Two aims
      are proposed in this study: first to compare the risk of developing delayed ICH
      after bilateral or unilateral frontal ICH, and second to determine the variables
      helpful to predict outcome according to the Glasgow Outcome Scale (GOS). Between
      January 1993 and December 1997, 694 consecutive patients with traumatic ICH were
      admitted to the Chang Gung Medical Center within 24 h of the trauma. Patients
      with ICH in sites other than the frontal lobes were excluded. A total of 161
      cases (mean age 46.3+/-20.3 years), including 57 bilateral (mean age 52.5+/-18.7
      years) and 104 unilateral (mean age 42.9+/-20.5 years) traumatic frontal ICH were
      studied. Twenty-eight of 57 patients (49%) with bifrontal ICH versus 17 of 104
      patients (16%) with unilateral frontal ICH had a further, delayed ICH. In 42 of
      45 patients (93%) with delayed ICH, this occurred within 5 days of the initial
      trauma. Multivariate logistic regression was used to select significant
      predictors of outcome. We found that delayed ICH (p<0.001), age (p=0.004) and
      mechanism of injury (p=0.001) explained the worse outcome in patients with
      bifrontal ICH. The best-fitting logistic regression model included three
      variables: delayed ICH (p=0.011), initial GCS (p=0.023), and a sum score of
      clinical and radiological variables (p=0.003). Bifrontal ICH tended to occur in
      older patients after a fall and was associated with a higher risk of developing
      delayed ICH or brain stem compression compared to unilateral ICH damage. Using
      these three variables - delayed ICH, initial GCS, and the sum score - in a
      logistical regression model is useful to predict outcome in patients with
      traumatic frontal ICH and may aid patient management.

PMID- 15519862
TI  - Critical relationship between sodium valproate dose and human teratogenicity:
      results of the Australian register of anti-epileptic drugs in pregnancy.
AB  - To compare the incidence of foetal malformations (FMs) in pregnant women with
      epilepsy treated with different anti-epileptic drugs (AED) and doses, and the
      influence of seizures, family and personal history, and environmental factors. A
      prospective, observational, community-based cohort study. METHODS: A voluntary,
      Australia-wide, telephone-interview-based register prospectively enrolling three
      groups of pregnant women: taking AEDs for epilepsy; with epilepsy not taking
      AEDs; taking AEDs for a non-epileptic indication. Four hundred and fifty eligible
      women were enrolled over 40 months. Three hundred and ninety six pregnancies had
      been completed, with 7 sets of twins, for a total of 403 pregnancy outcomes.
      RESULTS: 354 (87.8%) pregnancy outcomes resulted in a healthy live birth, 26
      (6.5%) had a FM, 4 (1%) a death in utero, 1 (0.2%) a premature labour with
      stillbirth, 14 (3.5%) a spontaneous abortion and 4 lost to follow-up. The FM rate
      was greater in pregnancies exposed to sodium valproate (VPA) in the first
      trimester (16.0%) compared with those exposed to all other AEDs (16.0% vs. 2.4%,
      P < 0.01) or no AEDs (16.0% vs. 3.1%, [Formula: see text] ). The mean daily dose
      of VPA taken in pregnancy with FMs was significantly greater than in those
      without (1,975 vs. 1,128 mg, P < 0.01). The incidence of FM with VPA doses >or=
      1,100 mg was 30.2% vs. 3.2% with doses <1,100 mg (P <0.01). CONCLUSIONS: There is
      a dose-effect relationship for FM and exposure to VPA during the first trimester
      of pregnancy, with higher doses of VPA associated with a significantly greater
      risk than with lower doses or with other AEDs. These results highlight the need
      to limit, where possible, the dose of VPA in pregnancy.

PMID- 15519863
TI  - Intracavernous carotid artery aneurysms.
AB  - Six patients with intracavernous carotid artery aneurysms (ICCAAns) were seen at
      our department from 1998 to 2002. All patients had only one intracranial aneurysm
      and their ages at diagnosis ranged from 36 to 72 years (median 56). Five were
      women and four had a history of hypertension. One patient was pregnant. All of
      the ICCAAns were symptomatic at diagnosis. Duration of symptoms was 2-30 days. On
      admission to our department, initial symptom was headache in four patients,
      visual loss in two, eye pain in one, third nerve paresis in two and subarachnoid
      hemorrhage (SAH) in one. Spontaneous thrombosis was present in two patients. All
      of the ICCAAns were saccular. Computed tomography (CT) was superior when compared
      with magnetic resonance imaging (MRI) for diagnosis of ICCAAns on admission.
      Angiography remains the gold standard for diagnosis and determination of specific
      anatomical details, which are necessary to plan treatment.

PMID- 15519864
TI  - Experience of a single institution treating foramen magnum meningiomas.
AB  - Despite the introduction of skull base approaches, there is still controversy in
      the optimum surgical management of foramen magnum meningiomas. Between January
      1990 and January 2003, 22 patients underwent 23 surgical procedures with a
      diagnosis of foramen magnum meningioma at Marmara University, Department of
      Neurosurgery. The suboccipital approach was used for 2 posteriorly located tumors
      with radiological total removal. The paramedian suboccipital approach was
      replaced by the far-lateral modification in the treatment of ventral meningiomas.
      1 of the 20 ventral tumors was operated twice. The classical suboccipital
      approach was followed by the far-lateral modification. A gross-total removal was
      achieved in 21 patients. The overall morbidity was 32%. No specific and
      clinically significant complications attributable to the far-lateral modification
      were observed. The far-lateral approach has improved the success of surgery in
      ventrally located lesions. The posterior suboccipital approach is still indicated
      in the removal of lesions placed posterior to the dentate ligament.

PMID- 15519865
TI  - Non-transcallosal ipsilateral area 3b responses to median nerve stimulus.
AB  - We report two patients with left hemisphere lesions who had no normal left
      hemispheric responses to right median nerve stimulus on magnetoencephalography
      but displayed right area 3b responses. One patient had suffered a severe left
      hemispheric contusion and the other left hemispheric infarction. Equivalent
      current dipoles of these ipsilateral responses were detected on the central
      sulcus adjacent to the location of the N20m response to left median nerve
      stimulus. The somatosensory afferent pathway from the hand may extend directly to
      the ipsilateral area 3b without following the transcallosal pathway in at least
      part of the population.

PMID- 15519866
TI  - Australian norms for a quantitative olfactory function test.
AB  - Quantitative olfactory assessment is often neglected in clinical practice,
      although olfactory loss can assist diagnosis and leads to significant morbidity.
      The aim of this study was to develop normative data for the Australian population
      for the 'Sniffin' Sticks', an internationally established olfactory function
      test. As in other populations, Australian females performed better than males and
      both lost olfactory function with age. From the normative data, criterion test
      scores for males and females were established for clinical classifications
      ('normosmic', 'hyposmic', and 'nosmic'). These clinical classifications were
      assessed in Parkinson's patients: 81.1% were anosmic or severely hyposmic and
      only 7.7% were normosmic. A new term ('rebyosmia') is introduced to describe age
      related loss of olfactory capacity of unknown aetiology. With these norms, the
      Sniffin' Sticks can be used in the Australian population to compare an
      individual's olfactory function against the population of others of similar age
      and sex and to identify olfactory dysfunction.

PMID- 15519867
TI  - Correlation of injury severity and tissue Evans blue content, lipid peroxidation
      and clinical evaluation in acute spinal cord injury in rats.
AB  - OBJECTIVE: To demonstrate the changes in microvascular permeability occurring in
      association with graded acute spinal cord injury and to determine whether tissue
      Evans blue content is a useful indicator of the severity of spinal cord injury.
      The study also aimed to test the ability of the Evans blue method to demonstrate
      secondary injury after spinal cord contusion. METHODS: In step one of the study,
      spinal cord lipid peroxidation levels and spinal cord Evans blue content were
      evaluated at 2 h post-injury in five groups of rats: a control group, a
      laminectomy-only group and three trauma groups (10, 50, and 100 gcm). In step
      two, these rats were used for Evans blue assessment following clinical
      examination at 24 h post-injury. RESULTS: The laminectomy-only group showed no
      difference from the control group with regard to spinal cord lipid peroxidation
      levels, tissue Evans blue content, and clinical findings. Increase in spinal cord
      tissue Evans blue content and lipid peroxidation was correlated with increasing
      intensity of trauma. There was a negative correlation between trauma intensity
      and clinical findings, and there was an increase in spinal cord tissue Evans blue
      content at 24 h compared with that at 2 h. CONCLUSIONS: Determination of spinal
      cord tissue Evans blue content is a reliable, rapid, simple and inexpensive
      method that can be used in experimental spinal cord injury to assess the severity
      of injury and to evaluate neuroprotection studies. The present study is the first
      to show that the Evans blue technique is a useful method to demonstrate secondary
      injury of spinal cord tissue and vasculature.

PMID- 15519868
TI  - Elevated ankyrin G in a plexiform neurofibroma and neuromas associated with pain.
AB  - Ankyrin G has recently been shown to be responsible for activation of sodium
      channels in the developing and regenerating axonal membrane. Via this sodium
      channel mechanism, elevated ankyrin G levels have been linked with spontaneous
      ectopic hyperexcitability and thus with pain phenomena in nervous tissue. Ankyrin
      G, a transmembrane, structural protein of the axon, was examined in four
      conditions: (a) painful plexiform neurofibroma; (b) painful neuroma; (c) non
      painful neuromas; (d) normal nerve. Neurofibroma tissue was obtained from an 18
      year old male patient who developed an intensely painful, plexiform neurofibroma
      of the posterior femoral cutaneous nerve and subsequently underwent surgery.
      Sample proteins were separated by PAGE and labeled with anti-ankyrin G antibodies
      in a Western blot procedure. RESULTS: The ankyrin G band density (mug) of protein
      for the painful neurofibroma was 6014 and was 3557 for the painful neuroma as
      compared to 3041, 1988 and 606 (mean+/-SD=1878+/-1221) for the three non-painful
      neuromas. Ankyrin G expression in normal nerves (8 specimens from 7 patients) was
      comparatively less (mean+/-SD=411+/-339). CONCLUSION: Our results may represent
      the first evidence for abnormally increased levels of ankyrin G protein with
      painful neurofibromas. Due to ankyrin G's multifunctional role in the development
      and remodeling of excitable membranes, it can be hypothesized that the
      significant increase contributes to the development of hyperexcitable axonal
      membranes in neurofibromas and potentially other peripheral pain conditions.

PMID- 15519869
TI  - Management of acute odontoid fractures with single anterior screw fixation.
AB  - The use of anterior odontoid screw fixation has grown in popularity for the
      management of acute, unstable Anderson and d'Alonzo Type II and rostral Type III
      odontoid fractures. This study critically reviews our clinical experience of 48
      patients with single odontoid screw fixation for the treatment of Type II and
      Type III odontoid fractures between 1997 and 2001. This series had a complication
      rate of 10% (malposition rate 6% and non-union rate 4%), with a satisfactory
      overall fusion rate of 96%. Odontoid screw fixation is technically demanding and
      requires strict patient selection, thorough preoperative planning and careful
      surgical technique. In our experience, advanced age should not be considered a
      contraindication to anterior odontoid screw fixation, as satisfactory results can
      be obtained in some of these patients. This study also emphasises that sagittally
      oblique type II fractures are associated with a high rate of fusion failure when
      treated by anterior odontoid screw fixation, and should be treated with other
      instrumentation methods, such as posterior atlantoaxial arthrodesis.

PMID- 15519870
TI  - Treatment of vertebral artery dissecting aneurysms presenting with progressive
      myelopathy.
AB  - Two patients with vertebral artery dissecting aneurysm are presented in which the
      posterior inferior cerebellar artery (PICA) arose from the wall of the aneurysm.
      The patients presented with progressive myelopathy due to mass effect on the
      medulla. One patient was treated with proximal occlusion of the vertebral artery
      using Guglielmi detachable coils (GDCs). The other patient underwent complete
      excision of the aneurysm, with reimplantation of the PICA into the vertebral
      artery proximal to the dissecting aneurysm. We obtained good results with
      improvement of myelopathy in both patients, but the patient who underwent bypass
      surgery suffered longstanding palsy of the lower cranial nerves. This report
      emphasizes that complete aneurysm clipping or excision for such patients is the
      gold standard of treatment, but preservation of PICA flow may require technically
      sophisticated surgical techniques. However, even if the aneurysm is not
      completely eliminated, the myelopathy can be dramatically improved with
      conservative endovascular treatment with proximal occlusion. Therefore, the
      choices for treatment in such lesions varies with the angiographic findings,
      degrees of mass effect on the brainstem, and the patient's physical condition.

PMID- 15519871
TI  - Cervical spondylosis with thoracic level Brown-Sequard syndrome.
AB  - Brown-Sequard Syndrome (BSS) caused by cervical spondylosis (CS) is rare. About
      70% of patients with CS presenting with BSS show lesion-dermatome discrepancy,
      which may be due to spinal cord lamination. From the clinical point of view, this
      discrepancy should be carefully evaluated and these patients should be treated as
      an emergency.

PMID- 15519872
TI  - Meningitis and Pneumocephalus. A rare complication of external
      dacryocystorhinostomy.
AB  - Meningitis due to fracture of the fovea ethmoidalis during external
      dacryocystorhinostomy is a rare complication. We report a case of pneumocephalus
      and meningitis in a 51-year-old female who underwent an external
      dacryocystorhinostomy (DCR). Although extracranial complications during or after
      external DCR have been well-described, only one case of meningitis has been
      reported in the literature. Physical examination, computerised tomography, lumbar
      puncture, and bacteriologic cultures were used to make the diagnosis. The patient
      responded well to antibiotic therapy. Her symptoms resolved immediately and she
      was discharged on the 21st post-operative day. This complication emphasises the
      importance of careful surgical technique and a thorough knowledge of regional
      anatomy, during DCR and similar procedures.

PMID- 15519873
TI  - Overriding fifth finger: an unusual sign in lower brachial plexopathy.
AB  - Hand deformities are often useful clinical signs. To our knowledge, they have not
      been described in association with brachial plexus lesions. A 28-year-old female
      presented with sudden left shoulder pain and medial forearm parasthesia.
      Examination showed the left fifth finger adducting and flexing over the dorsal
      aspect of the fourth finger. Neurophysiological studies and MRI supported a
      brachial plexus lesion. The physical sign was not present 5 months post onset and
      the patient experienced near complete clinical improvement. The unusual physical
      sign occurred in association with neuralgic amyotrophy. Its occurrence can be
      explained in terms of transient patchy involvement of nerve fascicles in the
      brachial plexus.

PMID- 15519874
TI  - Fibrous dysplasia of the frontal sinus: an uncommon cause of frontal lobe
      abscess.
AB  - Fibrous dysplasia of the cranial air sinuses is rarely reported in the
      literature. This is the first report of frontal lobe abscess (FLA) associated
      with fibrous dysplasia of the frontal sinus (FDFS). A 29-year-old female
      presented with seizures and acute confusion. Cranial computed tomography (CT)
      revealed fibrous dysplasia of the left frontal sinus and associated FLA. She was
      referred to the neurosurgical service and the abscess and dysplastic tissue were
      removed. Histological examination confirmed fibrous dysplasia. We review the
      radiological appearance of FDFS with FLA. Clinicians should be aware of the
      association between these two conditions.

PMID- 15519875
TI  - Peritumoural haematoma and meningioma: a common tumour with an uncommon
      presentation.
AB  - Spontaneous peritumoural haemorrhage in meningiomas is a rare but serious
      complication with a grave prognosis. It occurs at the interface between the
      tumour and the parenchyma, either from the tumour surface or the cortical vessels
      in association with it. Although several pathophysiologic mechanisms for this
      complication have been proposed, they all remain speculative. We report a 72-year
      old female who presented with sudden onset of headache and a left homonymous
      hemianopia. Neuroimaging revealed a parasagittal meningioma at the posterior
      third of the superior sagittal sinus with peritumoural intracerebral haematoma, 1
      cm away from the tumour. An uncomplicated gross total excision of the meningioma
      and aspiration of the haematoma was achieved through a craniotomy. The
      postoperative course was uneventful with an excellent clinical outcome. Possible
      mechanisms for this unusual complication are discussed. We emphasise the
      importance of prompt diagnosis and simultaneous excision of the tumour and
      aspiration of the haematoma as prerequisites for a favourable outcome.

PMID- 15519876
TI  - Cervical subdural empyema following acupuncture.
AB  - A review of the literature reveals only a few cases of spinal subdural empyema.
      Etiologies of spinal subdural empyema include hematogenous spread from skin
      lesions, systemic sepsis, direct spread from spinal osteomyelitis and
      complications of discography. However, in this report, we describe a patient who
      developed spinal subdural empyema following several cervical acupuncture
      sessions. Operative treatment with adequate laminectomy, removal of abscess, and
      copious irrigation resulted in good recovery. Microbiologic culture study of pus
      obtained at surgery was positive for Staphylococcus aureus. The need for
      sterilization procedures for acupuncture is emphasized and a brief review of the
      relevant literature is presented.

PMID- 15519877
TI  - Solitary intraspinal lumbar vertebral osteochondroma: a case report.
AB  - 1-4% of osteochondromas involve the spine. They are commonly found in the
      posterior elements of the vertebra and can cause radicular symptoms. We report a
      35 year-old man, suffering from right leg pain, which became worse over five
      years. His neurological examination revealed a positive right straight leg
      raising test and L4-L5 hypoesthesia. Lumbar computerised tomography (CT) and
      magnetic resonance imaging (MRI) studies revealed an exophytic, pedunculated bony
      projection. Osteochondroma should be considered while evaluating a patient with
      low back pain or radiculopathy without a CT or MRI appearance of a herniated
      lumbar disc.

PMID- 15519878
TI  - Intracerebellar granulocytic sarcoma complicating acute myelogenous leukemia: a
      case report and review of the literature.
AB  - Granulocytic sarcoma is a solid mass composed of premature precursors of
      granulocytic series cells in an extramedullary region. Intraparenchymal central
      nervous system localization without skull or meningeal invasion is extremely
      rare. Although different theories have been proposed to explain the mechanism of
      this unusual disorder, its exact mechanism is still unclear. Some degree of
      improvement can be achieved after surgery and radiotherapy but its prognosis is
      poor and most patients die within months. Nine cases of purely intraparenchymal
      granulocytic sarcomas have been reported in the literature. Here, we report the
      tenth case and review the current literature.

PMID- 15519879
TI  - Cerebral metastases in malignant mesothelioma: case report and literature review.
AB  - Malignant mesothelioma is an uncommon tumour with an inevitably poor outcome.
      Statistics from the US National Cancer Institute reveal a steady rise in its
      incidence over the past 25 years. It typically arises from the pleura, but can
      also originate in the peritoneum, pericardium, genital tracts and tunica
      vaginalis. Previously considered a local disease with low incidence of
      metastasis, there is increasing evidence suggesting otherwise. Reported cases of
      cerebral metastasis are rare and the vast majority are postmortem findings. This
      report documents a patient with symptomatic cerebral metastasis from malignant
      mesothelioma, who underwent craniotomy and excision of two cerebral lesions. It
      is one of a handful of case reports in the literature in which histological
      confirmation has been obtained ante-mortem and where surgical treatment of the
      intracranial mesothelioma was undertaken.

PMID- 15519880
TI  - Primary carnitine deficiency: adult onset lipid storage myopathy with a mild
      clinical course.
AB  - We studied two adult patients with myalgia and muscular fatigability during
      prolonged physical exercise. Serum creatine kinase was increased and muscle
      biopsy revealed a lipid storage myopathy affecting predominantly the type I
      fibres. Skeletal muscle carnitine content was reduced to 15% and 21% of the
      normal mean values, while serum carnitine levels were either normal or decreased.
      Four months of oral therapy with L-carnitine (3 g per day) resolved the clinical
      symptoms completely in both patients, and a subsequent muscle biopsy confirmed a
      marked reduction of lipid storage, along with increased muscle carnitine levels.
      The analysis of renal carnitine excretion and the exclusion of possible secondary
      carnitine deficiencies in both patients are compatible with mild defects of the
      carnitine transporter in one patient and of carnitine biosynthesis in the other.
      Since myalgia and muscular fatigue are frequent but unspecified complaints of
      otherwise clinically unremarkable adult patients, it is important to identify
      myopathies associated with primary carnitine deficiency because they may be
      amenable to treatment.

PMID- 15519881
TI  - Cerebral venous sinus thrombosis and thrombophilia presenting as pseudo-tumour
      syndrome following mild head injury.
AB  - Cerebral venous sinus thrombosis (CVT) after mild head injury is infrequent. A 38
      year-old patient presented with a Glasgow Coma score (GCS) of 15 after a road
      traffic accident. CT scan revealed a temporal contusion. He was treated with
      measures to prevent cerebral oedema and anticonvulsants. Three weeks later he
      presented with features of pseudo-tumour syndrome. Investigations revealed the
      presence of cerebral venous sinus thrombosis, protein C deficiency and elevated
      titres of antiphospholipid antibodies. He was treated with anticoagulants and
      showed improvement. This case report highlights that multiple "hits" may lead to
      CVT and hence laboratory screening of patients with CVT is necessary even if the
      clinical situation seemingly provides sufficient explanation for a thrombotic
      event. The presence of acquired and inherited causes of thrombophilia need not
      always lead to symptomatic thrombosis. As illustrated by this case, a second hit,
      such as trauma, may be the precipitating factor that unmasks the prothrombotic
      state.

PMID- 15519882
TI  - Supratentorial tanycytic ependymoma.
AB  - Tanycytic ependymoma is a rare fibrillary variant of ependymoma with a
      predilection for the spinal cord. We present an unusual supratentorial
      subcortical tanycytic ependymoma in a 17-year old male presenting with seizures.
      Only two other cases of subcortical tanycytic ependymoma have been reported.

PMID- 15519883
TI  - A case of hyperdense diploic epidermoid cyst on CT scan mimicking meningioma.
AB  - Epidermoid cysts typically have images characteristic similar to cerebrospinal
      fluid (CSF). A case of a hyperdense epidermoid cyst on computed tomography (CT)
      scan mimicking meningioma is described and the possibility of unusual imaging
      characteristics of epidermoids is highlighted as a diagnostic problem.

PMID- 15519884
TI  - Transient long segment spinal cord hyperintensity after anterior cervical
      discectomy.
AB  - A 69-year-old man was admitted to our hospital with progressive numbness in both
      feet and gait disturbance. MR imaging revealed a large cervical disc herniation
      resulting in significant spinal cord compression with hyperintensity of the
      spinal cord on T2-weighted images at C-5/6. Immediately after undergoing anterior
      cervical discectomy, the patient developed severe weakness of his left hand and
      lower extremities. MR imaging obtained 5 days after surgery revealed a long
      segment hyperintensity between C-3 and T-2 on T2-weighted images. This long
      segment hyperintensity disappeared after 2 weeks of steroid administration. We
      suspect that the persistent, localised, patchy C-5/6 cord hyperintensity
      represents spinal cord degeneration due to ischaemia and trauma resulting from
      the disc herniation. However, the transient long segment hyperintensity may
      represent oedema, probably due to minor trauma of an already compromised cord,
      during the decompression surgery. Clinicians should be aware that even careful
      surgery can result in a significant change in radiological studies and
      neurological condition.

PMID- 15519885
TI  - Jamieson "Ladye Jayne" temporary vascular clip and applicator (Cushing/Cairns
      artery forceps).

PMID- 15519886
TI  - The role of the AT1 angiotensin receptor in cardiac hypertrophy: angiotensin II
      receptor or stretch sensor?
AB  - Activation of the AT(1) angiotensin receptor is a clinically important
      maladaptive response during cardiac hypertrophy. Autocrine and paracrine effects
      of locally generated angiotensin II, are believed to be the main mediators of
      these responses. However, a recent report has suggested that mechanical stress
      can activate AT(1) receptors independently of angiotensin II generation. This
      finding, as well as recent studies on intracrine effects and the pharmacological
      consequences of receptor hetero-oligomerization, suggest that unexpected
      mechanisms could contribute to the role of the renin-angiotensin system during
      cardiac hypertrophy.

PMID- 15519887
TI  - Intranuclear organization and function of the androgen receptor.
AB  - We have entered an exciting era for androgen-receptor (AR) research that should
      provide a detailed description of how the AR functions as a ligand-regulated
      transcription factor. That AR activity is regulated by subcellular
      compartmentalization was first established a decade ago with the finding that
      binding of androgen to the AR induces its translocation from the cytoplasm to the
      nucleus. The contribution of compartmentalization to AR activity is, however,
      likely to extend beyond simple delivery to the nucleus. Defects in AR and
      coregulator compartmentalization in the nucleus have been demonstrated in
      prostate cancer, androgen-insensitivity syndrome, and spinal and bulbar muscular
      atrophy. A complete understanding of AR function and dysfunction in disease
      requires integrating transcription with the spatial and temporal regulation
      imposed by subnuclear organization and nuclear transport.

PMID- 15519888
TI  - 11beta-hydroxysteroid dehydrogenase type 1 as a modulator of glucocorticoid
      action: from metabolism to memory.
AB  - Increases in plasma cortisol and glucocorticoid pharmacotherapy cause myriad
      adverse effects from obesity and diabetes to impairments in memory. The common
      metabolic syndrome phenotypically resembles the rare disorder Cushing's syndrome,
      but plasma cortisol levels are usually normal. 11beta-Hydroxysteroid
      dehydrogenase type 1 (11beta-HSD1) catalyses the regeneration of active
      glucocorticoids (cortisol and corticosterone) from inert 11-keto forms in
      specific tissues, notably liver, adipose and brain. Recent work shows that obese
      humans and rodents have increased 11beta-HSD1 activity selectively in adipose
      tissue. By locally amplifying glucocorticoid action, this increase in activity
      might explain the Cushing's syndrome/metabolic syndrome paradox. Indeed, mice
      deficient in 11beta-HSD1 resist both the metabolic syndrome that develops with
      dietary obesity and glucocorticoid-associated cognitive impairments that develop
      with ageing. The ongoing development of selective 11beta-HSD1 inhibitors affords
      the opportunity to explore a new approach to some major common disorders.

PMID- 15519889
TI  - Effective treatments for insulin resistance: trim the fat and douse the fire.
AB  - Currently, only limited treatments are available for insulin resistance, a major
      cause of type 2 diabetes (T2D) and the metabolic syndrome. Combined innovative
      pharmaceutical and non-pharmaceutical strategies are needed. Obesity, a major
      cause of insulin resistance in T2D, can be treated relatively safely with modern
      bariatric surgery. Exercise training to increase VO(2max) is an important non
      pharmaceutical approach to decrease insulin resistance. The thiazolidinediones
      are useful in treating insulin resistance, but newer agents with broader
      specificity might be more efficacious without deleterious side effects. Recently
      oxidative stress has been implicated in insulin resistance. One antioxidant that
      is safe and appears effective is alpha-lipoic acid. Thus, combinations of
      surgery, exercise training, insulin sensitizers and antioxidants will probably
      constitute future insulin resistance management.

PMID- 15519890
TI  - The backdoor pathway to dihydrotestosterone.
AB  - Dihydrotestosterone (DHT) is the androgen responsible for formation of the male
      external genitalia during embryogenesis and for most androgen-mediated events at
      male puberty. In most circumstances, testosterone (T) derived from the testis is
      converted to DHT by 5alpha-reductase type 2 in genital skin and prostate. By
      contrast, the testes of pouch young of the tammar wallaby and immature postnatal
      testes of several species synthesize 5alpha-androstane-3alpha,17beta-diol, which
      is the proximal precursor of DHT in androgen-target tissues. Human steroidogenic
      enzymes efficiently catalyze all the required steps in a route to DHT that does
      not involve the T intermediate, called the 'backdoor pathway'. This alternative
      pathway of DHT production appears to explain how potent androgens are produced in
      some normal and pathological conditions when the conventional androgen
      biosynthetic pathways fail to account completely for the of patterns androgen
      synthesis that are observed.

PMID- 15519891
TI  - Cell-cell interactions at the ectoplasmic specialization in the testis.
AB  - During spermatogenesis, the movement of developing germ cells across the
      seminiferous epithelium involves the restructuring of adherens junctions that
      form between Sertoli cells and between Sertoli and germ cells such as the
      ectoplasmic specialization (ES). At the ultrastructural level, the ES has been
      thoroughly studied for the past three decades. Until recently, however,
      relatively little has been known about the molecular architecture, not to mention
      the mechanism, that regulates the ES. Recent findings in the field have
      highlighted several areas of research that deserve attention in future studies.
      For example, proteins that constitute the ES can be targeted to compromise cell
      adhesion. This approach will not only provide a better understanding of ES
      dynamics, but also will yield innovative approaches for the development of male
      contraceptives.

PMID- 15519892
TI  - GPR54 and puberty.
AB  - At puberty, pulsatile secretion of hormones initiates sexual maturation of the
      gonads. The G-protein-coupled receptor GPR54 is crucially involved in the
      initiation of puberty, along with its ligand metastin. Mice lacking GPR54 fail to
      undergo puberty and have immature reproductive organs and low levels of sex
      steroids and gonadotrophic hormones, but have normal levels of gonadotrophin
      releasing hormone in the hypothalamus. In humans, several cases of hypogonadism
      have been ascribed to mutations in GPR54. Production of metastin and, to a lesser
      extent, GPR54 are negatively regulated by testosterone and oestrogen, and
      injecting GPR54 ligands can increase hormone secretion in rodents. Thus, GPR54 is
      required for normal functioning of the hypothalamic-pituitary-gonadal axis,
      probably at the level of gonadotrophin-releasing-hormone secretion.

PMID- 15519893
TI  - CART in feeding and obesity.
AB  - CART (cocaine- and amphetamine-regulated transcript) peptides are
      neurotransmitters that have received much attention as mediators of feeding
      behavior and body-weight regulation in mammals. CART peptides and their mRNAs are
      found in many brain regions and in peripheral tissues that are involved in
      feeding, and many animal studies implicate CART as an inhibitor of feeding.
      Animal studies also demonstrate that CART expression is regulated by both leptin
      and glucocorticoids, two hormones known to be associated with the regulation of
      body weight. A recent study also links a mutation in the CART gene to obesity in
      humans. These peptides might become targets for drug development in the area of
      obesity.

PMID- 15519894
TI  - Body mass index and mortality among US male physicians.
AB  - PURPOSE: To assess the relationship between body mass index and mortality in a
      population homogeneous in educational attainment and socioeconomic status.
      METHODS: We analyzed the association between body mass index (BMI) and both all
      cause and cause-specific mortality among 85,078 men aged 40 to 84 years from the
      Physicians' Health Study enrollment cohort. RESULTS: During 5 years of follow-up,
      we documented 2856 deaths (including 1212 due to cardiovascular diseases and 891
      due to cancer). In age-adjusted analyses, we observed a U-shaped relation between
      BMI and all-cause mortality; among men who never smoked a linear relation was
      observed with no increase in mortality among leaner men (P for trend, <0.001).
      Among never smokers, in multivariate analyses adjusted for age, alcohol intake,
      and physical activity, the relative risks of all-cause mortality increased in a
      stepwise fashion with increasing BMI. Excluding the first 2 years of follow-up
      further strengthened the association (multivariate relative risks, from BMI<20 to
      > or = 30 kg/m2, were 0.93, 1.00, 1.00, 1.16, 1.45, and 1.71 [P for trend,
      <0.001]). In all age strata (40-54, 55-69, and 70-84 years), never smokers with
      BMIs of 30 or greater had approximately a 70% increased risk of death compared
      with the referent group (BMI 22.5-24.9). Higher levels of BMI were also strongly
      related to increased risk of cardiovascular mortality, regardless of physical
      activity level (P for trend, <0.01). CONCLUSIONS: All-cause and cardiovascular
      mortality was directly related to BMI among middle-aged and elderly men.
      Advancing age did not attenuate the increased risk of death associated with
      obesity. Lean men (BMI<20) did not have excess mortality, regardless of age.

PMID- 15519895
TI  - Maternal exposure to biomass smoke and reduced birth weight in Zimbabwe.
AB  - PURPOSE: To examine the association between household use of biomass fuels for
      cooking and birth weight. METHODS: Analysis is based on 3559 childbirths in the 5
      years preceding the 1999 Zimbabwe Demographic and Health Survey. Birth weights,
      recorded by trained professionals at local health clinics, were derived from
      health cards at home or from mother's recall. Multiple regression method was used
      to estimate the effect of household use of biomass cooking fuels (wood, dung, or
      straw) on birth weight, after controlling for child's sex and birth order,
      mother's education and nutritional status, pregnancy care, household living
      standard, and other potentially confounding factors. RESULTS: Babies born to
      mothers cooking with wood, dung, or straw were 175 g lighter (95% CI,-300,-50),
      on average, compared with babies born to mothers using LPG, natural gas, or
      electricity. The difference was 120 g (95% CI,-301, 61) for children whose birth
      weights were taken from health cards, and 183 g (95% CI,-376, 10) for children
      whose birth weights were reported by mothers. CONCLUSIONS: Household use of high
      pollution cooking fuels may cause reduced birth weight. The relationship needs to
      be further investigated using more direct measures of smoke exposure and birth
      weight and accounting for environmental tobacco smoke.

PMID- 15519896
TI  - Does vasectomy reversal protect against prostate cancer?

PMID- 15519897
TI  - Age, alcohol consumption, and all-cause mortality.
AB  - PURPOSE: Numerous epidemiological studies on middle aged men suggest that
      moderate alcohol consumption lowers all-cause mortality. Uncertainty exists
      whether this finding also applies to younger adults. METHODS: The authors studied
      the age specific association between alcohol consumption and all-cause mortality
      in a cohort of 19,943 male employees in the German construction industry (age
      range 25-64 years) who underwent an occupational health examination between 1986
      and 1992 and were followed with respect to vital status over an average period of
      10 years. Information on alcohol consumption at baseline examination relied on
      self report and strongly correlated with biological markers of alcohol
      consumption. Covariates considered in the proportional hazard regression analysis
      included age, nationality, smoking status, and comorbidity. RESULTS: Age specific
      analysis revealed that the J/U-shaped association between alcohol consumption and
      all-cause mortality is limited to men aged 35 years and above. In contrast, a
      linear positive dose-response relationship was observed for men aged 25 to 34
      years (p-trend=0.02). CONCLUSIONS: Recommendations regarding alcohol consumption
      and potential health benefits should not be generalized to all ages.

PMID- 15519898
TI  - Calibration of a semi-quantitative food frequency questionnaire in early
      pregnancy.
AB  - PURPOSE: We assessed the validity of a semi-quantitative food frequency
      questionnaire (FFQ) among pregnant women. METHODS: We enrolled 72 African
      American and 132 Caucasian pregnant women in a calibration study of an existing
      FFQ. For eight categories of intake of fatty acids, carotenoids, and gamma-
      tocopherol estimated by the FFQ (energy-adjusted deciles 1, 2, 3, 4+5, 6+7, 8, 9,
      10) we compared measurements of the corresponding nutrient level measured in
      pooled blood specimens from all participants in each category. RESULTS: For alpha
      carotene, plasma levels were 1.9 (p=0.10) and 2.9 (p=0.0007) microg/L higher for
      every 100 microg increase in dietary intake among African American and Caucasian
      women, respectively. A high percent increase in plasma levels was apparent
      between extreme dietary deciles of alpha-carotene (275% for African American and
      152% for Caucasian women). Increases across deciles were evident for lycopene,
      lutein, and gamma-tocopherol, ranging from 12% to 64%. We also observed
      relationships between dietary intake and their erythrocyte concentrations of long
      chain n-3 fatty acids and trans-fatty acids, but not alpha-linolenic acid.
      CONCLUSION: The observed differences in biomarkers across varying levels of
      dietary intake suggest that this FFQ is an appropriate epidemiologic tool for
      assessing intake of at least several important nutrients during early pregnancy
      in both African American and Caucasian women.

PMID- 15519899
TI  - Ischemic stroke hospital stay and discharge destination.
AB  - PURPOSE: Stroke hospitalizations are among the most expensive, with a mean length
      of stay (LOS) higher than other hospitalizations. This retrospective study
      assesses factors influencing ischemic stroke LOS taking into consideration the
      discharge destination of patients. METHODS: Linked hospital separation records
      between July 1995 and December 1999 were extracted to determine the first
      admission for ischemic stroke in Western Australia. Multiple hospitalization
      records for the same patient were screened to obtain the total duration of
      hospitalization. Demographic characteristics, hospital type, and medical history
      of patients were also retrieved. In the presence of censoring and without prior
      assumption on the time-to-discharge distribution, the Cox's proportional hazards
      model was used to assess the factors affecting LOS. RESULTS: During the study
      period, 6469 patients with a first-ever admission for ischemic stroke were
      identified, with average LOS being 28 days (95% CI, 26-30 days). Hospital stays
      were significantly longer for females and patients directly admitted to hospitals
      maintaining a specialist stroke unit, whereas patients residing in rural areas
      had shorter stays. CONCLUSIONS: The impact of stroke severity and placement in
      nursing homes after discharge need to be understood to manage LOS and the cost of
      acute care. Accurate diagnosis upon initial presentation would benefit both the
      efficiency of hospitals and the outcomes of rural ischemic stroke patients.

PMID- 15519900
TI  - Impact of season of food frequency questionnaire administration on dietary
      reporting.
AB  - PURPOSE: Foods consumed near the time of food frequency questionnaire (FFQ)
      administration may prime the memory, such that FFQ responses emphasize recently
      consumed foods. This study investigates the effect of season of FFQ
      administration, a proxy for the recent diet, on FFQ responses. METHODS: FFQ data
      from 74,958 Shanghai Women's Health Study (SWHS) subjects were compared with FFQ
      data from these subjects by season of FFQ administration (i.e., winter, spring,
      summer, and fall). All analyses were adjusted for age, BMI, and energy intake.
      Furthermore, quintile categories derived from all study subjects were compared
      with categories derived from the distribution of subjects recruited in the same
      season. RESULTS: Compared with the study group as a whole, subjects completing
      the FFQ in winter reported higher intakes of meat (2.1%), vegetable (3.9%), fish
      (3.1%), and soy foods (4.1%), but lower fruit (- 3.9%) intake. Subjects
      completing the FFQ in summer reported lower than average meat (- 2.0%), vegetable
      (- 3.2%), fish (- 2.3%), and soy food (- 4.6%) intakes, but greater fruit intake
      (0.9%). Completion of the FFQ in spring and fall usually led to intermediate
      differences from the group average, although fruit intake was 5.9% higher among
      subjects completing the FFQ in the fall. Variations across macronutrients and
      micronutrients by season of FFQ administration were smaller. If seasonal FFQ
      reporting is ignored, up to 13% of subjects would be classified to a different
      diet intake exposure category. However, reclassification was always to an
      adjacent category. CONCLUSIONS: FFQ responses varied with season of FFQ
      administration, consistent with theory that current diet intake influences
      reporting of habitual past diet intake. However, season of FFQ administration did
      not alter dietary exposure category assignments sufficiently to effect
      interpretation of most epidemiologic studies.

PMID- 15519901
TI  - Occupational risk factors associated with voice disorders among teachers.
AB  - PURPOSE: This study was designed to determine the occupational risk factors
      associated with voice disorders among schoolteachers, a high-risk population for
      developing voice problems. METHODS: Telephone interviews were completed by 1243
      teachers from Utah and Iowa. Response rates were 98% and 95%, respectively.
      Bivariate analyses were computed and assessed using chi-square test and Cochran
      Mantel-Haenszel test, and logistic regression analyses were performed and
      resulting odds ratios assessed using 95% confidence intervals. RESULTS: Teachers
      of vocal music, drama, other performing arts and chemistry were at significantly
      greater risk of having a voice disorder (OR=2.2, 95% CI: 1.2-4.0; OR=2.1, 95% CI:
      0.9-4.8; OR=1.6, 95% CI: 1.0-2.4; OR=2.0, 95% CI: 1.1-3.4), while teachers of
      special and vocational education had a significantly lower risk (OR=0.5, 95% CI:
      0.3-0.7; OR=0.6, 95% CI: 0.4-0.9). When adjusted for the intensity of
      vocalization, only teachers of chemistry were significantly at risk (OR=2.0, 95%
      CI: 1.1-3.5) while teachers of special education continued to have less of a risk
      (OR=0.5, 95% CI: 0.4-0.8). Chronic voice disorders were more prevalent among
      teachers of vocal music (OR=4.1, 95% CI: 2.2-7.9) and less prevalent among
      teachers of vocational education (OR=0.29, 95% CI: 0.09-0.95). CONCLUSIONS: These
      findings suggest that teachers of specific courses are at greater risk of
      developing a voice disorder.

PMID- 15519902
TI  - Epidemiological marker for oxidant status: comparison of the ELISA and the gas
      chromatography/mass spectrometry assay for urine 2,3-dinor-5,6-dihydro-15-F2t
      isoprostane.
AB  - PURPOSE: A biomarker of oxidant status applicable to epidemiological research is
      essential to studying the relationship between free radicals and chronic disease
      risk. Gas chromatography with mass-spectrometry detection (GC/MS) is the gold
      standard for measurement of urinary F2-isoprostanes (F2-isoPs), a non-invasive
      marker of oxidant status. However, this method is laborious and costly, which
      prohibits its use in large epidemiological studies. METHODS: We compared GC/MS
      assay with an inexpensive quick enzyme-linked immunoassay (ELISA) in measurements
      of 2,3-dinor-5,6-dihydro-15-F2t-isoprostane (F2-isoPM), an abundant beta
      oxidation metabolite of 8-iso-prostaglandin-F2alpha. We measured F2-isoPM in
      urine of 52 participants of the Insulin Resistance Atherosclerosis Study by both
      methods. RESULTS: The ELISA measurements showed approximately 30-fold greater
      mean and median (22.10, SD 12.92, and 18.49 ng/mg creatinine) than the GC/MS
      measurements (0.703, SD 0.468, and 0.597 ng/mg creatinine). We found low linear
      correlation (Pearson correlation coefficient 0.51; 95% CI, 0.28-0.70) and weak
      agreement in ranking subjects by tertiles (weighted Kappa statistic 0.34) between
      a GC/MS and ELISA. CONCLUSIONS: We conclude that the current ELISA method is not
      a valid substitute for the GS/MS assay.

PMID- 15519903
TI  - Murine models for the study of congestive heart failure: Implications for
      understanding molecular mechanisms and for drug discovery.
AB  - Congestive heart failure (CHF) is a complex illness of diverse aetiology. Despite
      the current multiple therapies, the prognosis for CHF patients remains poor, and
      new therapeutic targets need to be identified. With the advent of the genetic
      era, the mouse has become an increasingly valuable animal species in experimental
      CHF research. A large number of murine models of cardiac hypertrophy and CHF have
      been created by genetic engineering. Meanwhile, traditional CHF models created by
      coronary artery ligation, cardiac pressure, or volume overload have been adapted
      to mice. The present review categorizes and highlights the value of these murine
      models of cardiac hypertrophy and CHF. These models, combined with sophisticated
      physiological measurements of cardiac haemodynamics, are expected to yield more
      and valuable information regarding the molecular mechanisms of CHF and aid in the
      discovery of novel therapeutic targets.

PMID- 15519904
TI  - How to measure electrocardiographic QT interval in the anaesthetized rabbit.
AB  - Many drugs prolong QT or QU intervals [QT(U)] in the electrocardiogram (ECG), and
      this may be associated with the generation of drug-induced torsades de pointes.
      Therefore, it is essential to assess the ability of the newly developed drugs to
      prolong QT(U) interval. For this purpose, both in vivo and in vitro rabbit models
      are frequently used. However, it is very difficult to locate the end of the QT(U)
      interval in most rabbit ECGs when repolarisation is delayed, as the shape of the
      T and U waves may be deformed. In addition, as the heart rate of the rabbit is
      very high, the T (or U) wave may overlap the P wave or even the QRS complex of
      the following sinoatrial beat. In these circumstances, application of the
      "extrapolation method" makes it possible to determine the length of the QT(U)
      interval. This article describes the extrapolation method, shows ECG examples of
      typical T and U waves in the anaesthetized rabbit, and makes an attempt to
      provide a useful guide for researchers to measure reliably and reproducibly the
      duration of the QT(U) interval in rabbit studies.

PMID- 15519905
TI  - The [3H]dofetilide binding assay is a predictive screening tool for hERG blockade
      and proarrhythmia: Comparison of intact cell and membrane preparations and
      effects of altering [K+]o.
AB  - INTRODUCTION: The human ether-a-go-go-related gene (hERG) encodes a potassium
      channel responsible for the cardiac delayed rectifier current (IKr) involved in
      ventricular repolarization. Drugs that block hERG have been associated with QT
      interval prolongation and serious, sometimes fatal, cardiac arrhythmias
      (including torsade de pointes). While displacement of [3H]dofetilide, a potent
      methanesulfonanilide hERG blocker, from cells heterologously expressing hERG has
      been suggested as a screening assay, questions have been raised about its
      predictive value. METHODS: To validate the utility of this assay as a screening
      tool, we performed a series of saturation and competition binding studies using
      [3H]dofetilide as ligand and either intact cells or membrane preparations from
      HEK 293 cells stably transfected with hERG K+ channels. The object of these
      experiments was to (1) compare binding Ki values for 22 hERG blockers using
      intact cells or membrane homogenates to determine whether maintaining cell
      integrity enhanced assay reliability; (2) evaluate the ability of different K+
      concentrations (2, 5, 10, 20, and 60 mM) to modulate hERG binding; and (3) to
      establish the predictive value of the assay by comparing Ki values from binding
      studies at 5 and 60 mM [K+]o to functional IC50 values for hERG current block
      using 56 structurally diverse drugs. RESULTS: We found (a) comparable Ki values
      in the intact cell and isolated membrane binding assays, although there were some
      differences in rank order; (b) increasing [K+]o lowered the Kd and increased the
      Bmax for [3H]dofetilide, particularly in the membrane assay; and (c) good
      correlation between binding Ki values and functional IC50 values for hERG current
      block. DISCUSSION: In conclusion, increasing K+ concentrations results in an
      increase in both [3H]dofetilide affinity for hERG and available binding sites,
      particularly when using membrane homogenates. There are no meaningful differences
      between Ki values when comparing intact cell versus membrane assay, neither are
      there meaningful trends with increasing [K+]o within assays. There is good
      correlation between binding Ki values and functional (whole-cell patch clamp)
      IC50 values at both 5 and 60 mM K+ concentrations (R2 values of .824 and .863,
      respectively). The simplicity, predictability, and adaptability to high
      throughput platforms make the [3H]dofetilide membrane binding assay a useful tool
      for screening and ranking compounds for their potential to block the hERG K+
      channel.

PMID- 15519906
TI  - QT interval measurement in the dog: chest leads versus limb leads.
AB  - INTRODUCTION: An accurate measurement of the QT interval is dependent on the
      accurate identification of the end of the T wave. Although chest leads have been
      recommended in dog toxicology studies, their use has not been widely put into
      practice, as shown by a recent survey on methodology for ECG collection in the
      pharmaceutical industry. Therefore, there is little published data on dog QT
      measurement from chest leads. METHODS: Electrocardiograms (ECGs) were taken from
      100 beagle dogs (50 males, 50 females), with the dogs restrained in a sling. On
      the day of recording, measurements were performed at time zero and 1 h later.
      Recordings were repeated 7 to 10 days later. QT interval measurements were taken
      simultaneously from Lead II and the chest Lead CV5RL. Heart rate was taken from
      Lead II. Statistical analyses included the calculation of a QT correction
      formula, comparison of the mean values and variability of QT and QTc measurements
      from Leads II and CV5RL, the comparison of T-wave polarity from both leads, and a
      power analysis for QT and QTc. RESULTS: The T wave was positive in almost all
      dogs (99/100) in the Lead CV5RL at all measurement periods, while it was either
      positive or negative in Lead II (64-75/100), and the incidence of positive T wave
      varied between measurement periods. The QT interval was significantly shorter
      (194+/-11 to 197+/-12 vs. 197+/-13 to 200+/-12 ms) when measured from the CV5RL
      lead at all recording periods and in both sexes. In addition, the standard
      deviation for QT measurement within each individual ECG record demonstrates less
      intra-animal variation when QT is measured from Lead CV5RL compared with Lead II
      (3.8 vs. 13.2 ms). The linear regression between QT and heart rate was improved
      when QT measurements were taken from CV5RL, as shown by the percentage of
      variability R2. DISCUSSION: Estimates of the sample sizes showed that fewer
      animals would be required to detect a change at both the high and the mid-doses
      when using the chest Lead CV5RL. Using Lead II, we are able to detect within
      animal changes of 10% in either QT or QTc; with Lead CV5RL, we are able to detect
      10% change in QT and 5% change in QTc.

PMID- 15519907
TI  - Caenorhabditis elegans as model system for rapid toxicity assessment of
      pharmaceutical compounds.
AB  - INTRODUCTION: The model organism Caenorhabditis elegans is widely used for
      genetic studies as well as a living biomonitor in ecotoxicology. In this study,
      we investigated whether C. elegans may represent a suitable model for rapid
      preliminary toxicity studies of pharmaceutical compounds. METHODS: For this
      purpose, we used the EGFR kinase inhibitors BIBU1361, BIBX1382, and an inactive
      chemical analogue BIBU1476. As a first parameter to score for toxicity, we
      determined lethality of the wild-type C. elegans strain N2 (Bristol) in the
      presence of the compounds. The transgenic C. elegans strain PC72 (lacZ, heat
      shock protein-16 [hsp-16] construct) was used as a report organism for toxic
      effects. PC72 expresses beta-Galactosidase which is induced by hsp-16 in direct
      response when exposed to toxic compounds. The expression of beta-Galactosidase in
      cells was subsequently visualized by histochemical staining with X-Gal. RESULTS:
      A rank order of potency with respect to lethality was established:
      BIBU1361>BIBX1382>>BIB1476. The induction of beta-Galactosidase was concentration
      dependent for each compound and demonstrated the same order of potency as
      observed for lethality. Furthermore, these compounds showed the same order for
      lethality in rodents, the first requirement of validation. DISCUSSION: These
      results indicate that wild-type C. elegans and the transgenic strain PC72 are
      both suitable models to determine the toxicity of pharmaceutical compounds. This
      approach allows for an easy and fast ranking of compound toxicity, which may lead
      to a more rational choice for further in vivo tests.

PMID- 15519908
TI  - A new method of quantifying glutathione levels in freshly isolated single
      superfused rat cardiomyocytes.
AB  - INTRODUCTION: Glutathione (GSH) is an important antioxidant in the heart whose
      content changes during cardiac insults. However, there are currently no methods
      for continuously monitoring free cytoplasmic GSH levels in single isolated and
      superfused cardiomyocytes exposed to normal and pathological conditions. METHODS:
      GSH was measured using CellTracker Blue CMAC (Molecular Probes), a member of a
      new family of thiol-sensitive dyes. The fluorescence of 5 microM CellTracker Blue
      CMAC was measured in various solutions containing glutathione-S-transferase and
      in freshly isolated single superfused cardiomyocytes using an inverted
      fluorescence microscope. The cardiomyocytes were isolated by standard procedures
      and loaded with either CellTracker Blue CMAC or monochlorobimane by 15 min of
      shaking incubation in the dark at room temperature followed by centrifugation
      with resuspension of the cells in dye-free media. Cell volume was calculated from
      the 3H2O and [14C]sucrose space. RESULTS: CellTracker Blue CMAC fluorescence was
      linearly proportional to 0-100 microM GSH, as described by the equation: Y =
      182.2 (X) + 681.6 (r2 = .99, P < .001). Fluorescence was not affected by changing
      the glutathione-S-transferase level, the calcium concentration, or the pH,
      neither was the fluorescence quenched by H2O2 or cyanide. Exposure of freshly
      isolated single superfused cardiomyocytes to oxidative stress in the presence of
      0-1 mM H2O2 caused a progressive decrease in cellular GSH. In contrast, brief
      exposure to metabolic inhibition in the presence of 2.5 mM NaCN evoked a
      significant increase in cardiomyocyte GSH followed by a return to control levels
      during washoff. In comparison to monochlorobimane, cells loaded with CellTracker
      Blue CMAC gave a stronger signal with better cellular retention of the probe.
      DISCUSSION: These results suggest that CellTracker Blue CMAC fluorescence will be
      a good tool for measuring GSH in freshly isolated single superfused
      cardiomyocytes because it shows the expected changes to oxidative stress and
      metabolic inhibition, and is reversible.

PMID- 15519909
TI  - An improved method for assaying phosphatidylcholine in mouse tissue.
AB  - INTRODUCTION: To measure levels of phosphatidylcholine (PtdCh) in various mouse
      tissues, we developed a rapid and precise method using high-performance liquid
      chromatography (HPLC) with electrochemical detection (ECD) and an immobilized
      enzyme column. To generate an example data set, the effect of methoxamine (an
      alpha1-adrenergic agonist) on the PtdCh levels was examined by this method in the
      artery and the submandibular gland of the mouse in vivo. METHODS: Under our
      modifications of the method of Zapata et al. [J. Neurosci. 18 (1998) 3597], the
      mixture of lipophilic choline metabolites (PtdCh, lyso-PtdCh, and sphingomyelin)
      extracted by chloroform from the tissue homogenate was dried without prior
      separation and hydrolyzed with free choline by a 1-N perchloric acid solution
      containing ethylhomocholine (an internal standard for choline assay) at 90
      degrees C for 1 h. Subsequently, the hydrolyzed mixture was injected directly
      into the HPLC system for PtdCh assay. RESULTS: The present method permitted PtdCh
      assay within 5 min in one chromatographic run. Recovery of an authentic PtdCh
      sample was 99% (n = 10). The within-run coefficients of variation for choline
      derived from PtdCh in the same tissue samples were 0.6% (n = 10) and 1.3% (n =
      30). Under the present method, the lowest and highest PtdCh values in tissue
      samples were about 2 micromol/g (eye ball) and 29 micromol/g (spinal cord),
      respectively. Methoxamine significantly decreased PtdCh levels and increased free
      choline levels in mouse artery and submandibular gland. DISCUSSION: Under the
      present sample processing procedure, the choline values originating from lyso
      PtdCh and sphingomyelin were much less than those originating from PtdCh
      hydrolysis. Thus, it was possible to inject the hydrolyzed mixture directly into
      the HPLC system for PtdCh assay. Since the present method provides simple, rapid,
      and highly reliable PtdCh determination, it is suitable for routine assay of
      PtdCh in a large number of samples.

PMID- 15519910
TI  - Cholemic transgenic mice: a novel animal model to investigate the effects of bile
      acids.
AB  - INTRODUCTION: Laboratory investigations into cholestatic liver disease and the
      effects of cholemia on organ function are long-standing subjects of scientific
      enquiry. A widely-used strategy to investigate these topics relies on animal
      based research using experimental animal models. Targeted inactivation of the
      spgp gene, the gene responsible for expressing the bile salt export pump (BSEP)
      in the hepatocyte canalicular membrane impairs the canalicular secretion of bile
      salts resulting in systemic cholemia. The results of in vitro experiments have
      established bile acids as pro-oxidants and the collection of unambiguous in vivo
      data on the pro-oxidant activity of bile acids in the existing models of cholemia
      cannot be done. Therefore, we decided to use these genetically modified mice to
      determine whether this model of cholemia has evidence of extrahepatic or systemic
      oxidative stress, one of the features of cholestatic liver disease. METHODS: The
      extent of lipid peroxidation in livers, kidneys, hearts and brains harvested from
      cholemic homozygous (spgp -/-) mice using the thiobarbituric acid reactive
      substances (TBARS) assay. The data were compared to equivalent data collected
      from heterozygous (spgp +/-) and control mice. RESULTS: We found (1) substantial
      increases in malondialdehyde (MDA) levels in the brains and hearts; (2) a
      moderate increase in MDA levels in the kidneys; and (3) no change in MDA levels
      in the livers of the homozygous cholemic mice compared to the control and
      heterozygous mice. DISCUSSION: The transgenic mouse model of cholemia has an
      intact enterohepatic circulation and is uncomplicated by the adverse consequences
      of hepatotoxins or biliary surgery. Hepatocellular injury, as well as plasma and
      tissue accumulation of bilirubin and other liver-derived compounds are also
      negligible. Although this preliminary study could not establish a causal
      relationship between cholemia and oxidative stress, we believe this model is
      worthy of further investigation to study the impact of short-term and long-term
      cholemia on diverse physiological and biochemical functions such as trying to
      establish a causal role for bile acids in the development of oxidative stress in
      cholestatic liver disease.

PMID- 15519911
TI  - Two-year outcome audit in an adult learning disability population with refractory
      epilepsy.
AB  - Current evidence suggests that epilepsy outcome for people with a learning
      disability is poor, with the majority remaining refractory to treatment. There is
      very little evidence from randomised controlled trials in this population and
      despite the many uncontrolled variables it is suggested that an outcome audit may
      be one method of adding to the evidence base. This audit reports on the outcome
      for 37 patients with learning disability and refractory epilepsy. All patients
      were seen for the first time before March 2001 and the mean number of seizures
      for the sample was 10.4 per month. The exit audit included all patients at a date
      2 years after their initial visit following a programme of medication changes.
      The mean seizure frequency had reduced to 5.9 per month. Ten patients had become
      seizure-free and 76% had experienced an improvement in seizure frequency overall.
      A simple questionnaire was administered to carers and relatives at the exit audit
      in an attempt to establish an impression of global changes in alertness,
      assertiveness and challenging behaviour following interventions. Sixty-five
      percent of patients were regarded as being more aware and interactive with their
      surroundings following medication changes and 49% were reported to be more
      assertive. Thirty percent presented with an increase in behaviours regarded as
      challenging and 22% were reported to present with less challenging behaviour. The
      results of this audit suggest that the outcome for the majority of patients with
      learning disability and refractory epilepsy may be better than that has been
      previously reported.

PMID- 15519912
TI  - Antiepileptic drug treatment in seizure-free mesial temporal lobe epilepsy
      patients with hippocampal sclerosis following selective amygdalohippocampectomy.
AB  - Retrospectively we analysed postoperative AED treatment in patients with mesial
      temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS) who were seizure free
      following selective amygdalohippocampectomy (AHE). In this subgroup, we compared
      the patients without AEDs with that in the entire series. RESULTS: During the
      year prior to surgery, in the MTLE-HS group, a mean of 2.3 +/- 0.8 AEDs were
      taken. The percentage of seizure-free MTLE-HS patients without AEDs increases to
      40% from the postoperative year 5 on. In the ILAE Class 1a (seizure- and aura
      free since surgery) at postoperative year 5 more than 60% and from postoperative
      year 7 on more than 90% have discontinued AED intake. CONCLUSION: These figures
      indicate that reduction and discontinuation of AEDs is the same in the subgroup
      "seizure-free MTLE-HS patients" compared to the entire series.

PMID- 15519913
TI  - The investigation of syncope.
AB  - Patients with syncope are usually referred to either neurology or cardiology
      clinics, yet the facilities for detailed syncope investigation are mostly in
      cardiac units. The diagnosis rests principally upon the history, but
      investigations may be required to support the clinical diagnosis. Close
      collaboration between the epilepsy clinician and a cardiologist is essential for
      effective investigation and safe management of syncope. It is frequently
      misdiagnosed and often erroneously treated as epilepsy. Furthermore, it is
      potentially a marker of sudden death when associated with certain cardiac
      disorders. Here we review the main syncope types and explore diagnostic
      approaches.

PMID- 15519914
TI  - Full neurologic recovery after fulminant thrombotic thrombocytopenic purpura with
      status epilepticus.
AB  - Thrombotic thrombocytopenic purpura (TTP) is an ischemic vasculopathy frequently
      associated with neurological dysfunction including seizures. However, status
      epilepticus (SE) has rarely been reported in this condition. We report on a 70
      year-old woman with fulminant TTP who developed convulsive SE despite high
      therapeutic serum levels of phenytoin and phenobarbital. Her electroencephalogram
      (EEG) was characterized by bilateral independent periodic lateralizing
      epileptiform discharges (BIPLEDs) propagating into clinical and electrographic
      seizures. She recovered completely after intensive plasmapheresis and treatment
      with pentobarbital induced coma for 5 days. This case illustrates that aggressive
      treatment with pentobarbital and plasmapheresis may prevent permanent neurologic
      deficits when TTP is complicated by SE and that periodic lateralizing
      epileptiform discharges (PLEDs) in this syndrome can be the manifestation of a
      reversible ischemic insult.

PMID- 15519915
TI  - The Department of Health Action Plan "Improving Services for People with
      Epilepsy": a significant advance or only a first step?
AB  - The government in England has supported the production of a number of reports on
      services for people with epilepsy over the last three or four decades but these
      have not come with any promise to provide resources or to achieve change. In
      recent years, the voluntary agencies have worked with government in undertaking
      some very worthwhile initiatives. The publication of the audit on epilepsy
      related deaths and the commitment of the Chief Medical Officer have led to the
      production of an Action Plan entitled "Improving Services for People with
      Epilepsy". This Plan covers many of the key issues in the management of epilepsy
      and is seen as an important first step towards actual improvement of services.
      There is certainly a consensus that improvement is necessary with too many people
      receiving inadequate diagnosis and management leading, in some cases, to
      avoidable morbidity and mortality. A critical overview of the Action Plan and a
      suggested 10-point model Action Plan are presented. Whether the further necessary
      steps following the Department of Health Action Plan will be taken, remains to be
      seen. All those responsible for the management and wellbeing of people with
      epilepsy very much hope that the required measures will be taken to ensure
      significant long-term improvements in services.

PMID- 15519916
TI  - The contribution of the EEG technologists in the diagnosis of Panayiotopoulos
      syndrome (susceptibility to early onset benign childhood autonomic seizures).
AB  - PURPOSE: To assess the contribution of the EEG technologists in the diagnosis of
      children with epileptic seizures. METHODS: We analysed the clinical information
      obtained by the EEG technologists from children with epileptic seizures and their
      parents, and assessed its value for the generation of a clinically useful EEG
      report and a plausible electroclinical diagnosis. Interviews were based on a
      qualitative questionnaire, and were videotaped. We focused on Panayiotopoulos
      syndrome (PS) because it has a high rate of misdiagnosis, usually for
      encephalitis or other severe cerebral insults. RESULTS: Between 1998 and 2001,
      424 EEG were performed in 308 children aged 1-14 years, of whom 228 (74%) had one
      or more epileptic seizures. We diagnosed PS in 14 children (6.1%), mainly based
      on clinical information. Three other had symptomatic ictal vomiting. In 9 of the
      14 children with PS, diagnosis was achieved by the information collected by the
      EEG technologist. Five of these children were being treated for encephalitis, and
      management was altered accordingly. In a further three children the diagnosis of
      PS was confirmed. CONCLUSION: These findings demonstrate that the contribution of
      the EEG technologists to the diagnosis of people with epilepsies can expand well
      beyond their established role of recording and describing an EEG. We propose that
      technologists should be actively involved in prospective electroclinical studies
      if carefully designed protocols are used.

PMID- 15519917
TI  - The pharmacokinetic inter-relationship of tiagabine in blood, cerebrospinal fluid
      and brain extracellular fluid (frontal cortex and hippocampus).
AB  - PURPOSE: Tiagabine is a unique antiepileptic drug with a novel mechanism of
      action. Whilst some limited data are available as to the peripheral blood
      pharmacokinetics of tiagabine, data regarding the kinetics of tiagabine in the
      central brain compartment are very limited. We therefore sought to investigate
      serum, cerebrospinal fluid (CSF) and frontal cortex and hippocampal extracellular
      fluid (ECF) kinetic inter-relationship of tiagabine in a freely moving rat model.
      METHODS: Adult male rats were implanted with either a jugular vein catheter and a
      cisterna magna catheter for blood and CSF sampling, respectively, or a blood
      catheter and a microdialysis probe in the hippocampus and frontal cortex (for ECF
      sampling). Tiagabine was administered intraperitoneal (i.p.) at 20 or 40 mg/kg
      and blood, CSF and ECF were collected at timed intervals for the measurement of
      tiagabine concentrations by high performance liquid chromatography. RESULTS:
      Tiagabine concentrations in blood and CSF rose linearly and dose-dependently and
      time to maximum concentration (Tmax) was 15 and 29 min, respectively. Mean
      CSF/serum tiagabine concentration ratios (range, 0.008-0.01) were much smaller
      than the mean free/total tiagabine concentration ratios in serum (0.045 +/-
      0.003). Entry of tiagabine into brain ECF (frontal cortex and hippocampus) was
      rapid with Tmax values of 31-46 min. Distribution of tiagabine in brain was not
      brain region specific with values in the frontal cortex and hippocampus being
      indistinguishable. Whilst elimination from CSF was comparable to that of serum,
      half-life (t(1/2)) values in ECF were three times longer. CONCLUSIONS: Tiagabine
      is associated with linear kinetic characteristics and with rapid brain
      penetration. However, CSF concentrations are not reflective of free non-protein
      bound concentrations in serum. The observation that tiagabine elimination from
      the brain is threefold slower than that seen in blood, may explain as to the
      relatively long duration of action of tiagabine.

PMID- 15519918
TI  - Spinal muscular atrophy and progressive myoclonic epilepsy: one case report and
      characteristics of the epileptic syndrome.
AB  - INTRODUCTION: Spinal muscular atrophies (SMAs) are a group of degenerative
      diseases primarily affecting the anterior horn cells of the spinal cord and motor
      cells of cranial nerve nuclei. Even if the clinical picture is mainly dominated
      by the diffuse muscular atrophy, in some cases, patients may show associated,
      atypical clinical features ("SMA plus"). In particular, the association of SMA
      and progressive myoclonic epilepsy (PME) has been rarely described. CASE REPORT:
      We present the clinical and electrophysiological data of a boy with childhood
      onset SMA associated with PME and reviewed cases of the literature. CONCLUSION:
      The association of SMA with PME may constitute a separate and, probably,
      genetically independent syndrome with unique clinical and electroencephalographic
      findings or, at least, a variant of a neurodegenerative or metabolic disease, due
      to yet unknown causes.

PMID- 15519919
TI  - Vagus nerve stimulation therapy: 5-year or greater outcome at a university-based
      epilepsy center.
AB  - OBJECTIVE: This retrospective study documented long-term outcome of patients
      receiving vagus nerve stimulation (VNS) therapy for pharmacoresistant epilepsy.
      METHODS: Medical charts of 28 patients implanted for 5 years or longer were
      reviewed for changes in seizure frequency after 1 year of VNS therapy and at
      follow up, which ranged from 5 to 7 years. Numbers of antiepileptic drugs (AEDs)
      taken by the patients were also computed at 1 year and follow up. One patient had
      died and one had discontinued VNS therapy; data were available for 26 patients.
      RESULTS: The median percent change in seizure frequency from baseline increased
      from -28% (P = 0.0053, Wilcoxon signed-rank test) at 12 months to -72% (P <
      0.0001) at follow up. Some patients whose seizure frequency was not reduced
      during the initial 12 months of VNS therapy did experience reductions in seizure
      frequency during the follow-up period. CONCLUSION: In this retrospective study,
      the effectiveness of VNS therapy increased over time. Physicians should be aware
      that response to VNS therapy may be delayed for some patients.

PMID- 15519920
TI  - Effects of levetiracetam on spike and wave discharges in WAG/Rij rats.
AB  - Effects of the novel anti-epileptic drug levetiracetam (50 and 100 mg/kg) on
      spike and wave discharges (SWDs) of WAG/Rij rats were studied. Levetiracetam
      decreased the incidence, average duration, total duration and peak frequency of
      the SWDs. There was no difference between the two doses. These results agree with
      results obtained in Genetic Absence Epilepsy Rat from Strasbourg (GAERS).
      Furthermore, the decrease of the SWD peak frequency might support the suggestions
      that levetiracetam might have a GABAergic mechanism of action.

PMID- 15519921
TI  - Cardiac asystole during a temporal lobe seizure.
AB  - The association between temporal lobe seizures and cardiac arrhythmias has been
      anecdotally reported in the literature. Ictal bradycardia and cardiac asystole
      are rare, and maybe underestimated. The physiological mechanism is poorly
      understood. We report a patient with left temporal lobe seizures who developed
      ictal bradycardia and cardiac asystole during a complex partial seizure and
      required a subsequent placement of a pacemaker.

PMID- 15519923
TI  - Complications of botulinum toxin A use in facial rejuvenation.
AB  - The esthetic application of botulinum toxin type A (Botox) is a safe treatment
      modality; nevertheless complications can occur as a result of patient-and
      physician-related factors. Fortunately, adverse effects and undesirable sequelae
      after Botox injections are temporary. Complications may be more serious in
      patients who have more severe rhytids (which require more Botox), previous facial
      plastic surgery (altered anatomy), and those who have pre-existing neuromuscular
      disease. The physician can reduce complications by using proper injection
      techniques, appropriate regional Botox dosing, and by being conservative in the
      overall approach to Botox-mediated facial rejuvenation.

PMID- 15519924
TI  - The use of Botox to treat glabellar rhytids.
AB  - The goal of the article is to allow a physician to become more familiar with
      Botox as a treatment of glabellar wrinkles. An overview of the anatomy of that
      region is reviewed. Evaluation of the facial muscles before treatment and
      injection technique is also covered.

PMID- 15519925
TI  - Rhytidectomy analysis: twenty years of experience.
AB  - Careful analysis of a rhytidectomy patient is an important aspect of facial
      plastic surgery. Surgeons and physicians are successful when they diagnose
      patients correctly and apply the correct treatment plan. The skilled facial
      plastic surgeon appropriately evaluates the patient physically and emotionally
      then performs the correct surgical maneuvers to achieve the desired results. The
      focus of this article is the senior author's 20 years of experience in analyzing
      faces, and the goal of this article is to assist surgeons in achieving
      postoperative patients who are happy and "natural looking."

PMID- 15519926
TI  - Clinical presentations of cutaneous melanoma.
AB  - Cutaneous melanoma is responsible for the majority of skin cancer deaths. Early
      and accurate detection are the most important means to improve patient survival.
      This article reviews the common clinical presentations of head and neck cutaneous
      melanoma, and discusses lesions that might be clinically mistaken for melanoma.

PMID- 15519927
TI  - Upper blepharoplasty in the Asian patient: the "double eyelid" operation.
AB  - Upper Blepharoplasty in the Asian eye is a challenging procedure. This article
      aims to provide more than a basic description of upper blepharoplasty in the
      Asian patient. A system for reliable construction on upper lid of a specific size
      and shape and a system for staged modification of the epicanthal fold are
      presented.

PMID- 15519928
TI  - African American rhinoplasty.
AB  - This article describes the topographic and surgical anatomy of the African
      American nose and the surgical techniques used in the authors' practice.

PMID- 15519929
TI  - Evaluation and treatment of deformities of the chin.
AB  - Chin deformities present commonly to the facial plastic surgeon. Proper
      evaluation of the face is essential to allow the surgeon to counsel the patient
      properly regarding optimal management of chin deformities. This article reviews
      such analysis and discusses treatment modalities, including both the use of chin
      implants and osseous genioplasty.

PMID- 15519930
TI  - A modern approach to nasal osteotomies.
AB  - A thorough understanding of the anatomy of the nose is paramount in rhinoplasty.
      Correction of deformities of the nasal vault presents a challenge to the facial
      plastic surgeon. Suboptimal aesthetic results may occur when either inadequate or
      excessive mobilization of the nasal bony-cartilaginous framework is performed.
      Furthermore, postoperative complications such as collapse of the nasal airway may
      occur. A number of techniques are available to appropriately mobilize and
      reposition the bony nasal vault. In this article, we will review pertinent
      anatomy, technical considerations and clinical perspectives on mobilization of
      the nasal bones.

PMID- 15519931
TI  - Structure approach in rhinoplasty.
AB  - Over the past decade, rhinoplasty techniques have moved away from excisional
      methods and focused more on repositioning and restructuring existing tissues.
      These changes in surgical technique were made in part because of some of the
      untoward long-term complications noted in noses that were treated with excisional
      techniques. The incidence of many of these complications is greater in patients
      with certain nasal anatomy. It is the responsibility of the surgeon to identify
      these anatomic variants and make necessary adjustments in surgical technique to
      avoid complications.

PMID- 15519932
TI  - Deep plane rhytidectomy: a personal evolution.
AB  - As the rhytidectomy procedure has evolved over the years, the understanding of
      facial anatomy and critical examination of results have lead to the adoption and
      modification of the deep plane technique by the senior author. Experience with
      the deep plane rhytidectomy technique has shown that reliable, safe, and
      effective results can be achieved consistently. The aesthetic benefit has
      increased particularly with respect to the nasolabial fold and the jowl, while
      complications have been few. The historical background, evolution, and details of
      the technique are presented.

PMID- 15519933
TI  - Current lasers in skin resurfacing.
AB  - Lasers are a useful tool to combat signs of aging, photodamage, and environmental
      effects on the skin. This article reviews the history, basic science,
      indications, clinical considerations, and procedural techniques of various
      ablative lasers.

PMID- 15519934
TI  - Endoscopic techniques for rejuvenation of the midface.
AB  - Esthetic facial rejuvenation has gained widespread acceptance among the general
      public. As more and younger patients seek facial rejuvenation, surgeons have been
      searching for improved techniques, providing longer-lasting, natural-appearing
      results while decreasing peri- and postoperative sequelae. Toward this end, the
      endoscope was adapted to esthetic facial surgery. The intent of this article is
      to provide (1) the author's bias to rejuvenation of the midface and (2) an in
      depth review in how the endoscope can be useful for selective rejuvenation of the
      midface.

PMID- 15519935
TI  - Management of the cleft lip deformity.
AB  - A congenital cleft lip is a deformity that has significant physical and
      psychologic impact. Many surgical repairs have been proposed for reconstruction
      of unilateral cleft lip deformities, including straight-line repairs and various
      forms of geometric flap repair. This article classifies cleft deformities and
      describes the history and specific techniques of unilateral cleft lip repair.
      Understanding and application of these techniques can aid the cleft surgeon in
      maximizing function and appearance of a child born with a cleft lip deformity.

PMID- 15519936
TI  - Detection and management of the unstable patient.
AB  - The vast majority of doctor-patient interactions in the field of facial plastic
      surgery are mutually rewarding. Unstable patients will be encountered, however,
      because of the psychological components of cosmetic surgery. The harm or chaos
      such patients cause can be minimized by an awareness of unstable patient
      characteristics, an effort to screen for unstable behavior potential, and
      development of plans and protocols to manage such patients when they are
      encountered.

PMID- 15519937
TI  - The last decade--complementary therapies in nursing and midwifery. The first
      decade--complementary therapies in clinical practice.

PMID- 15519938
TI  - The effects of slow-stroke back massage on anxiety and shoulder pain in elderly
      stroke patients.
AB  - This study explores the effect of slow-stroke back massages on anxiety and
      shoulder pain in hospitalized elderly patients with stroke. An experimental
      quantitative design was conducted, comparing the scores for self-reported pain,
      anxiety, blood pressure, heart rate and pain of two groups of patients before and
      immediately after, and three days after the intervention. The intervention
      consisted of ten minutes of slow-stroke back massage (SSBM) for seven consecutive
      evenings. One hundred and two patients participated in the entire study and were
      randomly assigned to a massage group or a control group. The results revealed
      that the massage intervention significantly reduced the patients' levels of pain
      perception and anxiety. In addition to the subjective measures, all physiological
      measures (systolic and diastolic blood pressures and heart rate) changed
      positively, indicating relaxation. The prolonged effect of SSBM was also evident,
      as reflected by the maintenance of the psycho-physiological parameters three days
      after the massage. The patients' perceptions of SSBM, determined from a
      questionnaire, revealed positive support for SSBM for elderly stroke patients.
      The authors suggest that SSBM is an effective nursing intervention for reducing
      shoulder pain and anxiety in elderly patients with stroke. From a nursing
      perspective, this nursing practice provides a challenge and an opportunity for
      nurses and family caregivers to blend alternative therapies with technology to
      provide more individualized and holistic patient care.

PMID- 15519939
TI  - Sharing the spirit of the policy agenda? Private complementary therapists'
      attitudes towards practising in the British NHS.
AB  - During recent years, complementary medicine (CM) has grown as a significant
      provider of health care in the UK, the majority of this provision being allocated
      through the small private business sector to privately paying clients. Given the
      substantial demand for CM, the government acknowledges its structural integration
      with orthodox medicine (OM) to be a logical progression. However, although the
      time frame, evidence bases and regulatory structures are as yet undetermined, key
      to the current emphasis on integration is an underlying assumption that private
      sector providers would be willing participants, potentially alongside nurses. In
      this context, using a combined questionnaire (n=426) and interview (n=49) survey,
      this paper makes an initial exploration and considers the current connections
      that private therapists have with OM and their attitudes towards collaborating
      with and working within the NHS. The majority of therapists claimed not to have
      existing business connections with NHS providers, though many stated that they
      had established some form of informal arrangements. In general, therapists were
      happy that they had experienced increasingly positive reactions from orthodox
      clinicians towards their therapies. The overwhelming majority of therapists were
      positive about the proposition of working within OM but did have certain
      reservations. Given the range and intensity of opinion found in this initial
      investigation, the paper concludes by signposting some substantive avenues of
      focused research inquiry on the structural integration of CM and OM.

PMID- 15519940
TI  - The use of acupuncture in maternity care: a pilot study evaluating the
      acupuncture service in an Australian hospital antenatal clinic.
AB  - This paper outlines an exploratory study charting the circumstances of use and
      patient perspectives regarding the acupuncture service offered in an antenatal
      clinic at an Australian public hospital. Study participants were recruited from
      women attending the antenatal clinic. Upon completion of their course of
      acupuncture treatment, 52 women were given a questionnaire, of which 37 (71%)
      were completed and returned. Of the 37 women who attended the acupuncture clinic,
      18 (49%) had previously used at least one form of complementary medicine/therapy.
      The most common reason for treatment was physiological symptoms including back
      pain, symphysis pubis dysfunction and sciatica. All 37 women stated that the
      acupuncture improved their well-being and this finding was statistically
      significant (P<0.001). These findings are offered as a means of identifying
      potential issues for future investigation in this under-researched area.

PMID- 15519941
TI  - Breech presentation: increasing maternal choice.
AB  - Pregnant women with a third trimester breech presentation are almost invariably
      offered Caesarean section as the mode of delivery of first choice, especially
      when external version has failed to turn the fetus to cephalic. However,
      increasingly women are resorting to alternatives, to avoid either operative
      delivery or manipulative intervention in late pregnancy. This paper reviews some
      of the options for women with breech presentation, focusing especially on
      integrating these options into conventional maternity care.

PMID- 15519942
TI  - Nursing students' opinions and knowledge about complementary and alternative
      medicine therapies.
AB  - The aim of this study was to determine the nursing students' opinions and
      knowledge of complementary and alternative medicine (CAM) therapies in Turkey. A
      descriptive study was conducted via questionnaire to a convenience sample of 276
      nursing students. Students expressed positive opinions about CAM therapies, but
      their personal knowledge about CAM therapies was limited. Many students (64.5%,
      n=178) indicated that they wanted CAM to be integrated into the nursing
      curriculum and used in clinical practice (62.3%, n=172). Although students
      expressed knowledge of massage, diet, vitamins, herbal products, and praying,
      they had limited knowledge of biofeedback. Nursing students knowledge and
      understanding about CAM therapies in general, was found to be limited. It is
      suggested that the inclusion of CAM within in the nursing curriculum would
      prepare nurses to respond to knowledgably to patient questions related to CAM
      therapies.

PMID- 15519943
TI  - Eye movement desensitization in fibromyalgia: a pilot study.
AB  - The purpose of this study was to investigate the effectiveness of eye movement
      desensitization (EMD) for the relief of pain, fatigue and anxiety and depression
      in fibromyalgia patients. Six Caucasian female patients (mean age=43.2 yr)
      participated in two treatment sessions. Outcome assessments included the
      Fibromyalgia Impact Questionnaire, Fatigue Scale, Beck Anxiety Inventory, and
      Beck Depression Inventory. In-session process measures included thermal
      biofeedback monitoring and subjective units of discomfort ratings of pain,
      stress, and fatigue. Four out of six subjects were considered treatment
      responders. Thermal biofeedback monitoring revealed an average increase in hand
      temperature of 5.4 degrees indicating a relaxation effect. At treatment
      termination, average scores decreased on the measures of anxiety (28.6%),
      depression (29.9%), fibromyalgia impact (12.6%), and fatigue (11.5%). At the 3
      month follow-up assessment, total reductions in average scores from pre-treatment
      baseline reflected further improvements on measures of anxiety (45.8%),
      depression (31.6%), fibromyalgia impact (19.2%), and fatigue (26.7%). Because EMD
      produced a somewhat automatic relaxation response with minimal patient
      participation, it may be especially useful when standard relaxation techniques
      fail.

PMID- 15519944
TI  - So you fancy a career in complementary therapies?
AB  - This interview highlights key issues nurses should be aware of when deciding
      whether or not to set up in private practice. Fiona Mantle raises a number of
      generic issues nurses may need to consider before choosing the pathway to private
      practice. Whilst the issues she highlights are not exhaustive, her aim is to
      direct potential practitioners to seek advice and guidance in order to make
      informed decisions about future careers in clinical practice with complementary
      and alternative medicines.

PMID- 15519945
TI  - Anecdotal obsessions? A comment on the use of anecdotes by the general media to
      support claims in CAM.

PMID- 15519946
TI  - Reading-related oculomotor testing and training protocols for acquired brain
      injury in humans.
AB  - Many individuals with acquired brain injury (ABI) report reading problems of
      oculomotor origin. These may include frequent loss of place, skipping of lines
      and difficulty shifting to the next line of print. We describe two protocols for
      the testing and training of reading-related eye movements in adult individuals
      with ABI (traumatic brain injury [TBI] and stroke with hemianopia), who
      experience oculomotor-based symptoms when reading. These protocols use objective
      eye movement recording techniques and computer-based stimulus presentation and
      analysis. One protocol tests and the other trains basic horizontal and vertical
      versional eye movements (fixation, saccades and pursuit), as well as reading eye
      movements using simulated single and multiple line dynamic arrays. In addition, a
      reading rating-scale questionnaire is administered before and after completion of
      training to assess subjective reading improvement. In all paradigms, the target
      consists of a 0.5 degrees luminous square, which is displayed on a computer
      monitor positioned 40 cm from the subject along the midline. All testing and
      training are conducted under binocular viewing conditions with optical correction
      in place. There are two modes of training: normal internal oculomotor visual
      feedback either alone (4 weeks) or in conjunction with external oculomotor
      auditory feedback (4 weeks) administered in a counterbalanced manner within each
      diagnostic group. Training is performed 1 h, twice weekly for the 8 weeks.
      Oculomotor testing is conducted before, midway and after training. Following
      training, reading-related eye movements and reading ability improved as assessed
      both subjectively and objectively. These protocols provide a systematic approach
      to the quantitative and comprehensive testing and training of reading-related eye
      movement skills and behaviors in the ABI population manifesting oculomotor-based
      reading dysfunctions. Furthermore, the training protocol results in the rapid
      remediation of the eye movement deficits, which appear to transfer to activities
      of daily living.

PMID- 15519947
TI  - Detection and semi-quantitative determination of low abundance GFAP mRNA in mouse
      brain by capillary electrophoresis coupled with laser-induced fluorescence.
AB  - The sensitivity of capillary electrophoresis coupled with laser-induced
      fluorescence (CE-LIF) was compared with conventional agarose gel electrophoresis
      ethidium bromide-UV method (AE-EUV) for detection and semi-quantitative
      determination of GFAP mRNA in mouse brain. GFAP expression was induced by the
      neurotoxin MPTP in C57BL mice. Serially diluted RNA samples (0.0003, 0.003, 0.03,
      0.3, and 3 microg total RNA) were subjected to RT-PCR and analyzed by both
      procedures. The integrated pixel density (AE-EUV) and peak area (CE-LIF) were
      directly proportional to the amount of RNA. However, the observed high
      sensitivity of CE-LIF suggests its potential application for detection and semi
      quantitative determination of low-abundance mRNA transcripts.

PMID- 15519948
TI  - Recombinant adeno-associated virus serotype 2 effectively transduces primary rat
      brain astrocytes and microglia.
AB  - Recombinant adeno-associated virus-2 (rAAV2) under control of the chicken beta
      actin promoter/truncated CMV enhancer (CBA) was investigated for its ability to
      transduce primary cultures of rat brain neurons, microglia and astrocytes. This
      vector was highly effective in all three cell types in heparin-sensitive manners
      (astrocytes, microglia and neurons transduced by >98%, 75%, and 95%,
      respectively). However, astrocytes co-cultured with neurons were not transduced.
      rAAV2/CBA is an important new method for genetic manipulation of brain cells,
      though this may be modulated by interactions among cell types.

PMID- 15519949
TI  - Assessment of cognitive functions in severely paralysed and severely brain
      damaged patients: neuropsychological and electrophysiological methods.
AB  - A systematic neuropsychological assessment technique is described for use with
      severely physically disabled individuals, possibly with combined motor and
      cognitive disorders. Target neurological conditions may be, e.g., an incomplete
      locked-in state, a minimally conscious state, or severe combinations of
      paralysis, agnosia, and apraxia. Neuropsychological assessment in these patients
      is difficult, because standard neuropsychological tests require fast motor
      responses, which can be manual, verbal, or both. To assess the cognitive status
      of patients with residual motor function, tests have been applied that can be
      answered by a binary (yes/no) signal and whose outcomes were not based on
      reaction times. Further, a battery of neurophysiological examination procedures
      based on event-related brain potentials has been developed. These procedures can
      be performed directly at a patient's bedside (at home or in a hospital) and
      applied for assessment of cognitive functions even in patients without residual
      motor function.

PMID- 15519950
TI  - A pre-clinical assessment model of rat autogeneic bone marrow stromal cell
      transplantation into the central nervous system.
AB  - In order to verify the biological aspects of 'autogeneic' bone marrow stromal
      cells (BMSC) transplantation for neurological disorders, we aimed our study
      towards the assessment of the survival, distribution, and differentiation of
      autologous BMSC in the central nervous system (CNS). We harvested rat BMSC from
      femur bones, and the nuclei were then fluorescently labeled by a 24-h co-culture
      with bis-benzimide. These BMSC were stereotactically injected into the striatum
      (n=6) or thoracic cord (n=8) of each animal. We evaluated the distribution and
      differentiation of 'autogeneic' BMSC in the brain and spinal cord after 4 weeks,
      using the immunohistochemistry technique. We found some injected cells in the
      ipsilateral striatum, hippocampus, neocortex, and bilateral corpus callosum, and
      approximately 20% and 15% of the engrafted cells expressed neuronal and
      astrocytic markers, respectively. Other injected cells were distributed in the
      dorsal funiculus and adjacent gray matter, and about 10% and 15% of these cells
      expressed neuronal and astrocytic markers, respectively. Although the precise
      mechanism of BMSC transdifferentiation still remains unclear, the present results
      show that 'autogeneic' BMSC could highly differentiate into their own CNS neural
      cells, suggesting that they are surrounded by favorable conditions.

PMID- 15519951
TI  - Use of frozen sections to determine neuronal number in the murine hippocampus and
      neocortex using the optical disector and optical fractionator.
AB  - Stereology is an important technique for the quantification of neurons in
      subregions of the central nervous system. A commonly used method of stereology
      relies upon embedment of tissue in glycol methacrylates to allow production of
      sections that are resistant to shrinkage in thickness. However, the use of glycol
      methacrylates for stereology has several disadvantages, including severe
      constraints on the size of tissue that can be processed and the long duration of
      time often required for infiltration. We describe a novel method of stereology
      utilizing tissue sections cut in the frozen state. This new methodology relies
      upon the staining of sections as free-floating sections and upon the mounting of
      these sections onto slides with a water-based mounting media. Sections cut in the
      frozen state and processed by these methods undergo little or no shrinkage in
      thickness and are ideal for stereological cell counts utilizing either the
      optical disector or optical fractionator methods of stereology. We demonstrate
      that frozen sections can be utilized to estimate neuronal number with high
      degrees of precision and with low coefficients of error. Because large tissue
      blocks can be cut as frozen sections, this method expands the range of tissues
      that can be processed efficiently for stereology and readily allows
      quantification of neurons from multiple brain regions from the same tissue
      sections. We applied this new methodology to estimate neuronal numbers in the
      neocortex and hippocampus of 10-day-old mice. The method was useful for
      estimation of both large, sparsely packed cell populations, such as the
      neocortex, and small, densely packed cells, such as the dentate gyrus granule
      cells. Thus, frozen section methodology offers many potential advantages over the
      use of glycol methacrylate embedment for stereology. These advantages include
      expansion of the size of tissue blocks that can be processed, reduction in
      expended time and costs, and ability to quantify multiple brain regions from a
      single set of sections.

PMID- 15519952
TI  - Meditation in health: an operational definition.
AB  - Despite its evergrowing use in health-related areas, procedures characterized as
      meditation have been little or not at all defined operationally, which hinders
      its use in a standardized manner. In the present study, the authors present a
      possible operational definition of meditation, which has been used in social and
      academic projects, developed in Universidade Federal de Sao Paulo. In this
      proposal, it is emphasized that, in order to be characterized as meditation, the
      procedure should encompass the following requirements: (1) the use of a specific
      technique (clearly defined), (2) muscle relaxation in some moment of the process
      and (3) "logic relaxation"; (4) it must necessarily be a self-induced state, and
      (5) use of "self-focus" skill (coined "anchor").

PMID- 15519953
TI  - Executive neurocognitive functioning and neurobehavioral systems indicators in
      borderline personality disorder: a preliminary study.
AB  - It is argued that borderline personality disorder (BPD) represents the
      interaction of underlying neurobehavioral systems that are reflected principally
      in the phenotypic constructs of positive emotion, negative emotion, and
      nonaffective constraint (Depue & Lenzenweger, 2001). This preliminary and
      exploratory study sought to examine predictions made from the Depue-Lenzenweger
      model with respect to controlled (effortful) information processing in BPD. It
      was hypothesized that (a) BPD subjects may display deficits on tasks that require
      controlled information processing (sustained attention, spatial working memory,
      and executive functioning), (b) they may reveal elevated negative emotion as well
      as decreased positive emotion and nonaffective constraint, and (c) nonaffective
      constraint should be substantially inversely associated with accurate performance
      on controlled information processing tasks. The results of this study, which
      examined 24 BPD diagnosed individuals and 68 normal adults, found support for
      each of these predictions in relation to performance on the Wisconsin Card
      Sorting Test. The implications of these results for further experimental
      psychopathology investigations of BPD as well as further refinement of
      theoretical models of the disorder are discussed.

PMID- 15519954
TI  - Borderline psychopathology in the first-degree relatives of borderline and axis
      II comparison probands.
AB  - The purpose of this study was to assess the prevalence of each of the nine DSM
      criteria for borderline personality disorder and the prevalence of the disorder
      itself in the first-degree relatives of borderline probands and Axis II
      comparison subjects. Four hundred and forty-five inpatients were interviewed
      about familial borderline psychopathology using the Revised Family History
      Questionnaire--a semistructured interview of demonstrated reliability. Of these
      445 subjects, 341 met both DIB-R and DSM-III-R criteria for BPD and 104 met DSM
      III-R criteria for another type of personality disorder (and neither criteria set
      for BPD). The psychopathology of 1,580 first-degree relatives of borderline
      probands and 472 relatives of Axis II comparison subjects was assessed. Both DSM
      III-R and DSM-IV BPD were found to be more common among the relatives of
      borderline than Axis II comparison probands. However, five of the criteria for
      BPD (inappropriate anger, affective instability, paranoia/dissociation, general
      impulsivity, and intense, unstable relationships) and all four sectors of
      borderline psychopathology (affect, cognition, impulsivity, and interpersonal
      relationships) were found to be both more common and discriminating than the BPD
      diagnosis itself. Taken together, the results of this study suggest that the
      subsyndromal phenomenology of BPD may be more common than the borderline
      diagnosis itself.

PMID- 15519955
TI  - A comparison of personality function among patients with seasonal depression,
      nonseasonal depression, and nonclinical participants.
AB  - Although a large body of research has accumulated concerning the relationship
      between nonseasonal depression and personality, comparatively few studies have
      examined the relationship between seasonal affective disorder (SAD) and
      personality. This study compared dimensional aspects of personality in patients
      diagnosed with SAD (N = 60), nonseasonal depression (N = 273), and nonclinical
      controls (N = 297) using the Dimensional Assessment of Personality Pathology
      (DAPP-BQ; Livesley & Jackson, in press). Analysis by ANCOVA indicated that
      significant between-group differences occurred in several of the 18 DAPP-BQ
      dimensions, with patients with SAD exhibiting personality psychopathology that
      was intermediate between the nonclinical sample and patients with nonseasonal
      depression. The results demonstrated that the traits associated with seasonal and
      nonseasonal depression differ in degree, not kind.

PMID- 15519956
TI  - Personality disorder and future-directed thinking in parasuicide.
AB  - Parasuicide patients have been found to lack positive expectations for the
      future. The aim of the present study was to look at variations in this lack of
      positive future-thinking as a function of personality status. A sample (N = 442)
      of repeat parasuicide patients was assessed on positive and negative future
      thinking and the presence of personality disorder or personality difficulty.
      Those with a Cluster B personality disorder (borderline or dissocial) were
      significantly lower in positive future-thinking than those with no Cluster B
      symptoms or those with Cluster B personality difficulty. Neither Cluster A nor
      Cluster C symptomatology was related to positive future-thinking. Negative future
      thinking was not significantly related to any type of personality disorder or
      difficulty. The results are interpreted as evidence of the importance of
      personality status in influencing positive future-thinking and gives some
      indications of why those with Cluster B personality disorder have such high rates
      of recurrent self-harm.

PMID- 15519957
TI  - Early maladaptive schemas in personality disordered individuals.
AB  - The present study aimed to examine the specificity of schema domains in three
      personality disorder (PD) groups, namely borderline (BPD), obsessive-compulsive
      (OCPD), and avoidant PD (AvPD), and to correctly identify the three PD groups on
      the basis of these schemas. The sample consisted of 48 clinical participants
      diagnosed with PDs and assigned to 1 of 3 groups on the basis of their Axis II
      diagnoses (BPD: n = 13; OCPD: n = 13; AvPD: n = 22). High scores on
      Dependence/Incompetence, Defectiveness/ Shame and Abandonment were found for the
      BPD group. Such pattern appears to be most consistent with Young's theory of BPD.
      Consistent with the theory and empirical findings of Beck et al. (1990, 2001),
      OCPD was associated with elevations on the Unrelenting Standards schema domain,
      but not on Emotional Inhibition, which was found to be elevated for AvPD. In
      conclusion, the present study suggests that there are different patterns of
      schema domains across different PDs and that the Schema Questionnaire (SQ) is
      potentially useful in differentiating between these PDs.

PMID- 15519958
TI  - A "little five" lexically based perspective on personality disorder symptoms in
      adolescence.
AB  - Recently, De Clercq and De Fruyt (2003) examined the relation between adaptive
      and maladaptive personality functioning in adolescence, using adult measures to
      describe adolescent personality and personality pathology, i.e., that is the
      NEOPI-R (Costa & McCrae, 1992) and the ADP-IV (Schotte & De Doncker, 1994)
      respectively. The present study extends this work, administering a lexically
      based and age-specific measure of adaptive personality, i.e., that is the
      Hierarchical Personality Inventory for Children (HiPIC; Mervielde & De Fruyt,
      1999), to 454 nonclinical adolescents. Results largely replicated across adult
      FFM versus lexically derived and age-specific measures, although HiPIC domains
      explained a larger proportion of disorder variance, with Benevolence and
      Conscientiousness especially demonstrating less descriptive specificity.
      Lexically derived facets were further helpful to achieve greater disorder
      descriptive specificity. Finally, adolescent personality pathology, when
      operationalized using Axis II criteria, showed more overlap in adolescence than
      in adults. It is concluded that future studies should focus on age-specific
      taxonomies and measures to assess personality pathology in adolescence.

PMID- 15519959
TI  - Pathological gambling and personality disorders: an exploratory study with the
      IPDE.
AB  - This article describes the most frequent personality disorders related to
      pathological gambling. Participants included 50 pathological gamblers assessed
      with the IPDE, and 50 normative subjects from the general population with the
      same demographic features (age, sex, and socioeconomic level). Thirty-two percent
      of the clinical sample (vs. the 8% of the normative sample) showed at least one
      personality disorder. The most prevalent disorders were Borderline (16%),
      followed by Antisocial, Paranoid, Narcissistic, and Non-specified (8% each).
      Gamblers with personality disorders presented an average of 1.5 disorders and
      they reported higher gambling severity and more severe symptoms of anxiety,
      depression and alcohol abuse. The implications of this study for clinical
      practice and research are discussed.

PMID- 15519960
TI  - Confidential reproductive health services for minors: the potential impact of
      mandated parental involvement for contraception.
AB  - CONTEXT: Recent legislative efforts to implement mandated parental involvement
      for minor adolescents seeking family planning services threaten the rights of
      adolescents younger than 18 to access reproductive health care. METHODS: State
      and federal laws and policies pertaining to minor adolescents' rights to access
      services for contraception and sexually transmitted diseases are reviewed, and
      research examining issues of parental involvement among adolescents using clinic
      based reproductive health services is synthesized. RESULTS: Attempts to mandate
      parental involvement for reproductive health care often focus on contraceptive
      services and are typically linked to federal or state funding. Studies of
      teenagers using clinic-based family planning services suggest that slightly more
      than one-half would obtain contraceptives at family planning clinics even if
      parental notification were required. Mandated parental involvement for
      contraception would discourage few teenagers from having sex, but would likely
      result in more teenagers' using the least effective methods, such as withdrawal,
      or no method at all. Family planning clinics encourage teenagers to voluntarily
      talk to their parents, but relatively little information is available about the
      extent to which activities to promote parent-child communication have been
      adopted. CONCLUSIONS: Mandated parental involvement for teenagers seeking
      contraceptive care would likely contribute to increases in rates of teenage
      pregnancy. Research that will help clinics implement and improve efforts to
      encourage voluntary parental involvement is urgently needed.

PMID- 15519961
TI  - Differences between mistimed and unwanted pregnancies among women who have live
      births.
AB  - CONTEXT: Mistimed and unwanted pregnancies that result in live births are
      commonly considered together as unintended pregnancies, but they may have
      different precursors and outcomes. METHODS: Data from 15 states participating in
      the 1998 Pregnancy Risk Assessment Monitoring System were used to calculate the
      prevalence of intended, mistimed and unwanted conceptions, by selected variables.
      Associations between unintendedness and women's behaviors and experiences before,
      during and after the pregnancy were assessed through unadjusted relative risks.
      RESULTS: The distribution of intended, mistimed and unwanted pregnancies differed
      on nearly every variable examined; risky behaviors and adverse experiences were
      more common among women with mistimed than intended pregnancies and were most
      common among those whose pregnancies were unwanted. The likelihood of having an
      unwanted rather than mistimed pregnancy was elevated for women 35 or older
      (relative risk, 2.3) and was reduced for those younger than 25 (0.8); the pattern
      was reversed for the likelihood of mistimed rather than intended pregnancy (0.5
      vs. 1.7-2.7). Parous women had an increased risk of an unwanted pregnancy (2.1
      4.0) but a decreased risk of a mistimed one (0.9). Women who smoked in the third
      trimester, received delayed or no prenatal care, did not breast-feed, were
      physically abused during pregnancy, said their partner had not wanted a pregnancy
      or had a low-birth-weight infant had an increased risk of unintended pregnancy;
      the size of the increase depended on whether the pregnancy was unwanted or
      mistimed. CONCLUSION: Clarifying the difference in risk between mistimed and
      unwanted pregnancies may help guide decisions regarding services to women and
      infants.

PMID- 15519962
TI  - Measuring factors underlying intendedness of women's first and later pregnancies.
AB  - CONTEXT: Unintended pregnancy is associated with poor health outcomes for mothers
      and infants, and is indicative of gaps in family planning services. Conventional
      measures of pregnancy intendedness do not reflect the multiple factors affecting
      a woman's pregnancy-related intentions and attitudes. METHODS: Data collected
      between March 2002 and February 2003 from 701 women in a public family planning
      clinic and 671 women in a public prenatal clinic in New Orleans were analyzed to
      examine factors underlying intendedness (including attitudes toward pregnancy and
      motivations to achieve or avoid pregnancy). RESULTS: In factor analyses,
      variables measuring pregnancy intendedness were represented by a single latent
      factor, pregnancy desirability. For first pregnancy, variables that best captured
      desirability were those measuring happiness, effort in achieving the pregnancy,
      extent of looking forward to telling friends, whether the pregnancy was intended
      (i.e., came at the right time or later), and whether the woman wanted to have a
      baby with her partner. For last or current pregnancies that were second or higher
      order ones, they were happiness, pregnancy wantedness, effort in achieving the
      pregnancy, whether the pregnancy was planned and whether the woman wanted to have
      a baby with her partner. Among women younger than 18 at first pregnancy,
      happiness and whether a woman wanted a baby with her partner were the only items
      that captured pregnancy desirability. CONCLUSIONS: Future surveys on pregnancy
      intendedness could reduce the number of questions used to capture pregnancy
      desirability. This should help standardize surveillance systems and permit better
      assessment of trends in pregnancy desirability over time.

PMID- 15519963
TI  - The availability and use of publicly funded family planning clinics: U.S. trends,
      1994-2001.
AB  - CONTEXT: It is important to monitor trends among publicly funded family planning
      clinics to determine where clinics are successfully meeting the contraceptive
      service needs of low-income women and where more effort is needed. METHODS:
      Service data for all U.S. agencies and clinics providing subsidized family
      planning services were collected for 2001 and compared with similar data
      collected for 1997 and 1994. Trends reflecting clinic structure and capacity were
      analyzed at the national and state levels. Client numbers were compared with
      numbers of women needing publicly funded contraceptive services to create a
      measure of met need for states and groups of states, according to Medicaid family
      planning waiver status. RESULTS: In 2001, some 7,683 publicly funded family
      planning clinics provided contraceptive services to 6.7 million women
      representing an 8% rise in clinics and a 2% increase in clients since 1994.
      Change varied by type of provider and clinic location. Health departments and
      Planned Parenthood affiliates served more clients at fewer sites; community
      health centers served fewer clients at more sites. One-third of states
      experienced growth in clinic capacity, with 5-65% increases in met need. In
      another third of states, met need declined by 5% or more. States with income
      based Medicaid family planning waivers served 24% more clients, with met need
      increasing from 40% to 50%. CONCLUSIONS: Among states, there has been tremendous
      variation in the ability of publicly funded family planning clinics to serve
      women. Implementation of income-based Medicaid family planning waivers in some
      states was associated with clinics' serving greater numbers of women. Further
      efforts are needed to ensure access to family planning services for low-income
      women in every state.

PMID- 15519964
TI  - Introduction and synthesis: Plant phylogeny and the origin of major biomes.
AB  - Phylogenetic trees based upon DNA sequence data, when calibrated with a dimension
      of time, allow inference of: (i) the pattern of accumulation of lineages through
      time; (ii) the time of origin of monophyletic groups; (iii) when lineages arrived
      in different geographical areas; (iv) the time of origin of biome-specific
      morphologies. This gives a powerful new view of the history of biomes that in
      many cases is not provided by the incomplete plant fossil record. Dated plant
      phylogenies for angiosperm families such as Leguminoaceae (Fabaceae),
      Melastomataceae sensu stricto, Annonaceae and Rhamnaceae indicate that long
      distance, transoceanic dispersal has played an important role in shaping their
      distributions, and that this can obscure any effect of tectonic history,
      previously assumed to have been the major cause of their biogeographic patterns.
      Dispersal from other continents has also been important in the assembly of the
      Amazonian rainforest flora and the Australian flora. Comparison of dated
      biogeographic patterns of plants and animals suggests that recent long-distance
      dispersal might be more prevalent in plants, which has major implications for
      community assembly and coevolution. Dated plant phylogenies also reveal the role
      of past environmental changes on the evolution of lineages in species-rich
      biomes, and show that recent Plio-Pleistocene diversification has contributed
      substantially to their current species richness. Because of the critical role of
      fossils and morphological characters in assigning ages to nodes in phylogenetic
      trees, future studies must include careful morphological consideration of fossils
      and their extant relatives in a phylogenetic context. Ideal study systems will be
      based upon DNA sequence data from multiple loci and multiple fossil calibrations.
      This allows cross-validation both of age estimates from different loci, and from
      different fossil calibrations. For a more complete view of biome history, future
      studies should emphasize full taxon sampling in ecologically important groups,
      and should focus on geographical areas for which few species-level phylogenies
      are available, such as tropical Africa and Asia. These studies are urgent because
      understanding the history of biomes can both inform conservation decisions, and
      help predict the effects of future environmental changes at a time when
      biodiversity is being impacted on an unprecedented scale.

PMID- 15519965
TI  - Global climate and the distribution of plant biomes.
AB  - Biomes are areas of vegetation that are characterized by the same life-form.
      Traditional definitions of biomes have also included either geographical or
      climatic descriptors. This approach describes a wide range of biomes that can be
      correlated with characteristic climatic conditions, or climatic envelopes. The
      application of remote sensing technology to the frequent observation of biomes
      has led to a move away from the often subjective definition of biomes to one that
      is objective. Carefully characterized observations of life-form, by satellite,
      have been used to reconsider biome classification and their climatic envelopes.
      Five major tree biomes can be recognized by satellites based on leaf longevity
      and morphology: needleleaf evergreen, broadleaf evergreen, needleleaf deciduous,
      broadleaf cold deciduous and broadleaf drought deciduous. Observations indicate
      that broadleaf drought deciduous vegetation grades substantially into broadleaf
      evergreen vegetation. The needleleaf deciduous biome occurs in the world's
      coldest climates, where summer drought and therefore a drought deciduous biome
      are absent. Traditional biome definitions are quite static, implying no change in
      their life-form composition with time, within their particular climatic
      envelopes. However, this is not the case where there has been global ingress of
      grasslands and croplands into forested vegetation. The global spread of grasses,
      a new super-biome, was probably initiated 30-45 Myr ago by an increase in global
      aridity, and was driven by the natural spread of the disturbances of fire and
      animal grazing. These disturbances have been further extended over the Holocene
      era by human activities that have increased the land areas available for domestic
      animal grazing and for growing crops. The current situation is that grasses now
      occur in most, if not all biomes, and in many areas they dominate and define the
      biome. Croplands are also increasing, defining a new and relatively recent
      component to the grassland super-biome. In the case of both grassland and
      croplands, various forms of disturbance, particularly frequent disturbance, lead
      to continued range extensions of the biomes.

PMID- 15519966
TI  - Assessing the quality of molecular divergence time estimates by fossil
      calibrations and fossil-based model selection.
AB  - Estimates of species divergence times using DNA sequence data are playing an
      increasingly important role in studies of evolution, ecology and biogeography.
      Most work has centred on obtaining appropriate kinds of data and developing
      optimal estimation procedures, whereas somewhat less attention has focused on the
      calibration of divergences using fossils. Case studies with multiple fossil
      calibration points provide important opportunities to examine the divergence time
      estimation problem in new ways. We discuss two cross-validation procedures that
      address different aspects of inference in divergence time estimation. 'Fossil
      cross-validation' is a procedure used to identify the impact of different
      individual calibrations on overall estimation. This can identify fossils that
      have an exceptionally large error effect and may warrant further scrutiny.
      'Fossil-based model cross-validation' is an entirely different procedure that
      uses fossils to identify the optimal model of molecular evolution in the context
      of rate smoothing or other inference methods. Both procedures were applied to two
      recent studies: an analysis of monocot angiosperms with eight fossil calibrations
      and an analysis of placental mammals with nine fossil calibrations. In each case,
      fossil calibrations could be ranked from most to least influential, and in one of
      the two studies, the fossils provided decisive evidence about the optimal
      molecular evolutionary model.

PMID- 15519967
TI  - Multiple Miocene Melastomataceae dispersal between Madagascar, Africa and India.
AB  - Melastomataceae sensu stricto (excluding Memecylaceae) comprise some 3000 species
      in the neotropics, 1000 in Asia, 240 in Africa, and 230 in Madagascar. Previous
      family-wide morphological and DNA analyses have shown that the Madagascan species
      belong to at least three unrelated lineages, which were hypothesized to have
      arrived by trans-oceanic dispersal. An alternative hypothesis posits that the
      ancestors of Madagascan, as well as Indian, Melastomataceae arrived from Africa
      in the Late Cretaceous. This study tests these hypotheses in a Bayesian
      framework, using three combined sequence datasets analysed under a relaxed clock
      and simultaneously calibrated with fossils, some not previously used. The new
      fossil calibration comes from a re-dated possibly Middle or Upper Eocene
      Brazilian fossil of Melastomeae. Tectonic events were also tentatively used as
      constraints because of concerns that some of the family's fossils are difficult
      to assign to nodes in the phylogeny. Regardless of how the data were calibrated,
      the estimated divergence times of Madagascan and Indian lineages were too young
      for Cretaceous explanations to hold. This was true even of the oldest ages within
      the 95% credibility interval around each estimate. Madagascar's Melastomeae
      appear to have arrived from Africa during the Miocene. Medinilla, with some 70
      species in Madagascar and two in Africa, too, arrived during the Miocene, but
      from Asia. Gravesia, with 100 species in Madagascar and four in east and west
      Africa, also appears to date to the Miocene, but its monophyly has not been
      tested. The study afforded an opportunity to compare divergence time estimates
      obtained earlier with strict clocks and single calibrations, with estimates based
      on relaxed clocks and different multiple calibrations and taxon sampling.

PMID- 15519969
TI  - Metacommunity process rather than continental tectonic history better explains
      geographically structured phylogenies in legumes.
AB  - Penalized likelihood estimated ages of both densely sampled intracontinental and
      sparsely sampled transcontinental crown clades in the legume family show a mostly
      Quaternary to Neogene age distribution. The mode ages of the intracontinental
      crown clades range from 4-6 Myr ago, whereas those of the transcontinental crown
      clades range from 8-16 Myr ago. Both of these young age estimates are detected
      despite methodological approaches that bias results toward older ages. Hypotheses
      that resort to vicariance or continental history to explain continental disjunct
      distributions are dismissed because they require mostly Palaeogene and older
      tectonic events. An alternative explanation centring on dispersal that may well
      explain the geographical as well as the ecological phylogenetic structure of
      legume phylogenies is Hubbell's unified neutral theory of biodiversity and
      biogeography. This is the only dispersalist theory that encompasses evolutionary
      time and makes predictions about phylogenetic structure.

PMID- 15519968
TI  - Historical biogeography of two cosmopolitan families of flowering plants:
      Annonaceae and Rhamnaceae.
AB  - Annonaceae are a pantropically distributed family found predominantly in
      rainforests, so they are megathermal taxa, whereas Rhamnaceae are a cosmopolitan
      family that tend to be found in xeric regions and may be classified as
      mesothermal. Phylogenetic analyses of these families are presented based on rbcL
      and trnL-F plastid DNA sequences. Likelihood ratio tests revealed rate
      heterogeneity in both phylogenetic trees and they were therefore made ultrametric
      using non-parametric rate smoothing and penalized likelihood. Divergence times
      were then estimated using fossil calibration points. The historical biogeography
      of these families that are species rich in different biomes is discussed and
      compared with other published reconstructions. Rhamnaceae and most lineages
      within Annonaceae are too young to have had their distribution patterns
      influenced by break-up of previously connected Gondwanan landmasses. Contrasts in
      the degree of geographical structure between these two families may be explained
      by differences in age and dispersal capability. In both groups, long-distance
      dispersal appears to have played a more significant role in establishing modern
      patterns than had previously been assumed. Both families also contain examples of
      recent diversification of species-rich lineages. An understanding of the
      processes responsible for shaping the distribution patterns of these families has
      contributed to our understanding of the historical assembly of the biomes that
      they occupy.

PMID- 15519970
TI  - Epiphytism and pollinator specialization: drivers for orchid diversity?
AB  - Epiphytes are a characteristic component of tropical rainforests. Out of the
      25,000 orchid species currently known to science, more than 70% live in tree
      canopies. Understanding when and how these orchids diversified is vital to
      understanding the history of epiphytic biomes. We investigated whether orchids
      managed to radiate so explosively owing to their predominantly epiphytic habit
      and/or their specialized pollinator systems by testing these hypotheses from a
      statistical and phylogenetic standpoint. For the first approach, species numbers
      of 100 randomly chosen epiphytic and terrestrial genera were compared.
      Furthermore, the mean number of pollinators per orchid species within the five
      subfamilies was calculated and correlated with their time of diversification and
      species richness. In the second approach, molecular epiphytic orchid phylogenies
      were screened for clades with specific suites of epiphytic adaptations. Epiphytic
      genera were found to be significantly richer in species than terrestrial genera
      both for orchids and non-orchids. No evidence was found for a positive
      association between pollinator specialization and orchid species richness.
      Repeated associations between a small body size, short life cycle and specialized
      clinging roots of twig epiphytes in Bulbophyllinae and Oncidiinae were
      discovered. The development of twig epiphytism in the first group seems
      repeatedly correlated with speciation bursts.

PMID- 15519971
TI  - Origins of the southeastern Australian vegetation.
AB  - Australia is an ancient continent with an interesting geological history that
      includes a recent major shift in its position, both globally and compared with
      neighbouring land masses. This has led to a great deal of confusion over many
      years about the origins of the Australian biomes. The plant fossil record is now
      clarifying this, and it is clear that the ancient Gondwanan rainforests that
      covered Australia while it was still part of that supercontinent contained many
      of the elements of the modern vegetation. However, major climatic sifting, along
      with responses to other factors, including soil nutrient levels, disturbance
      regimes, atmospheric CO2 levels, fire frequency and intensity, glaciations and
      the arrival of humans, have had profound impacts on the Australian vegetation,
      which today reflects the sum of all these factors and more. The origins of
      Australian vegetation and its present-day management cannot be properly
      understood without an appreciation of this vast history, and the fossil record
      has a vital role to play in maintaining the health of this continent's vegetation
      into the future.

PMID- 15519972
TI  - Radiation of the Australian flora: what can comparisons of molecular phylogenies
      across multiple taxa tell us about the evolution of diversity in present-day
      communities?
AB  - The Australian fossil record shows that from ca. 25 Myr ago, the aseasonal-wet
      biome (rainforest and wet heath) gave way to the unique Australian sclerophyll
      biomes dominated by eucalypts, acacias and casuarinas. This transition coincided
      with tectonic isolation of Australia, leading to cooler, drier, more seasonal
      climates. From 3 Myr ago, aridification caused rapid opening of the central
      Australian arid zone. Molecular phylogenies with dated nodes have provided new
      perspectives on how these events could have affected the evolution of the
      Australian flora. During the Mid-Cenozoic (25-10 Myr ago) period of climatic
      change, there were rapid radiations in sclerophyll taxa, such as Banksia,
      eucalypts, pea-flowered legumes and Allocasuarina. At the same time, taxa
      restricted to the aseasonal-wet biome (Nothofagus, Podocarpaceae and
      Araucariaceae) did not radiate or were depleted by extinction. During the
      Pliocene aridification, two Eremean biome taxa (Lepidium and Chenopodiaceae)
      radiated rapidly after dispersing into Australia from overseas. It is clear that
      the biomes have different histories. Lineages in the aseasonal-wet biome are
      species poor, with sister taxa that are species rich, either outside Australia or
      in the sclerophyll biomes. In conjunction with the fossil record, this indicates
      depletion of the Australian aseasonal-wet biome from the Mid-Cenozoic. In the
      sclerophyll biomes, there have been multiple exchanges between the southwest and
      southeast, rather than single large endemic radiations after a vicariance event.
      There is need for rigorous molecular phylogenetic studies so that additional
      questions can be addressed, such as how interactions between biomes may have
      driven the speciation process during radiations. New studies should include the
      hitherto neglected monsoonal tropics.

PMID- 15519973
TI  - Palaeobotanical studies from tropical Africa: relevance to the evolution of
      forest, woodland and savannah biomes.
AB  - Fossil plants provide data on climate, community composition and structure, all
      of which are relevant to the definition and recognition of biomes. Macrofossils
      reflect local vegetation, whereas pollen assemblages sample a larger area. The
      earliest solid evidence for angiosperm tropical rainforest in Africa is based
      primarily on Late Eocene to Late Oligocene (ca. 39-26 Myr ago) pollen assemblages
      from Cameroon, which are rich in forest families. Plant macrofossil assemblages
      from elsewhere in interior Africa for this time interval are rare, but new work
      at Chilga in the northwestern Ethiopian Highlands documents forest communities at
      28 Myr ago. Initial results indicate botanical affinities with lowland West
      African forest. The earliest known woodland community in tropical Africa is dated
      at 46 Myr ago in northern Tanzania, as documented by leaves and fruits from lake
      deposits. The community around the lake was dominated by caesalpinioid legumes,
      but included Acacia, for which this, to my knowledge, is the earliest record.
      This community is structurally similar to modern miombo, although it is different
      at the generic level. The grass-dominated savannah biome began to expand in the
      Middle Miocene (16 Myr ago), and became widespread in the Late Miocene (ca. 8 Myr
      ago), as documented by pollen and carbon isotopes from both West and East Africa.

PMID- 15519974
TI  - Mechanisms and tempo of evolution in the African Guineo-Congolian rainforest.
AB  - This paper reviews how and when African rainforest diversity arose, presenting
      evidence from both plant and animal studies. Preliminary investigations show that
      these African forests are an assemblage of species of varying age. Phylogenetic
      evidence, from both African rainforest angiosperms and vertebrates, suggest a
      Tertiary origin for the major lineages in some of these groups. In groups where
      savannah species are well represented and rainforest species are a minority, the
      latter appear to be relics of a Mid-Tertiary rainforest. By contrast, species
      that are primarily adapted to rainforest have arisen in the past 10 Myr with the
      main morphological innovations dating from the Late Miocene, and Quaternary
      speciation dominating in large, morphologically homogeneous groups. The small
      number of species-level phylogenies for African rainforest plants hinders a more
      incisive and detailed study into the historical assembly of these continental
      forests.

PMID- 15519975
TI  - South American palaeobotany and the origins of neotropical rainforests.
AB  - Extant neotropical rainforest biomes are characterized by a high diversity and
      abundance of angiosperm trees and vines, high proportions of entire-margined
      leaves, high proportions of large leaves (larger than 4500 mm2), high abundance
      of drip tips and a suite of characteristic dominant families: Sapotaceae,
      Lauraceae, Leguminosae (Fabaceae), Melastomataceae and Palmae (Arecaceae). Our
      aim is to define parameters of extant rainforests that will allow their
      recognition in the fossil record of South America and to evaluate all known South
      American plant fossil assemblages for first evidence and continued presence of
      those parameters. We ask when did these critical rainforest characters arise?
      When did vegetative parameters reach the level of abundance that we see in
      neotropical forests? Also, when do specific lineages become common in neotropical
      forests? Our review indicates that evidence of neotropical rainforest is
      exceedingly rare and equivocal before the Palaeocene. Even in the Palaeocene, the
      only evidence for tropical rainforest in South America is the appearance of
      moderately high pollen diversity. By contrast, North American sites provide
      evidence that rainforest leaf physiognomy was established early in the
      Palaeocene. By the Eocene in South America, several lines of evidence suggest
      that neotropical rainforests were diverse, physiognomically recognizable as
      rainforest and taxonomically allied to modern neotropical rainforests. A mismatch
      of evidence regarding the age of origin between sites of palaeobotanical high
      diversity and sites of predicted tropical climates should be reconciled with
      intensified collecting efforts in South America. We identify several lines of
      promising research that will help to coalesce previously disparate approaches to
      the origin, longevity and maintenance of high diversity floras of South America.

PMID- 15519976
TI  - The role of immigrants in the assembly of the South American rainforest tree
      flora.
AB  - The Amazon lowland rainforest flora is conventionally viewed as comprising
      lineages that evolved in biogeographic isolation after the split of west Gondwana
      (ca. 100 Myr ago). Recent molecular phylogenies, however, identify immigrant
      lineages that arrived in South America during its period of oceanic isolation
      (ca. 100-3 Myr ago). Long-distance sweepstakes dispersal across oceans played an
      important and possibly predominant role. Stepping-stone migration from Africa and
      North America through hypothesized Late Cretaceous and Tertiary island chains may
      have facilitated immigration. An analysis of inventory plot data suggests that
      immigrant lineages comprise ca. 20% of both the species and individuals of an
      Amazon tree community in Ecuador. This is more than an order of magnitude higher
      than previous estimates. We also present data on the community-level similarity
      between South American and palaeotropical rainforests, and suggest that most
      taxonomic similarity derives from trans-oceanic dispersal, rather than a shared
      Gondwanan history.

PMID- 15519977
TI  - Evolution of the species-rich Cape flora.
AB  - The Cape Floristic Region ('fynbos biome') has very high levels of plant species
      diversity and endemism. Much of this diversity is concentrated in a relatively
      small number of clades centered in the region (Cape clades), and these form a
      vegetation called 'fynbos'. The general explanation for the origin of this
      diversity is that much of it evolved in the Pliocene and Late Miocene in response
      to progressive aridification. We present a phylogenetic analysis of an almost
      complete species sample of the largest clade of Restionaceae, the third largest
      Cape clade. This indicates that the radiation of the Restionaceae started between
      20 and 42 Myr ago, and since then there were no, or at most gradual, changes in
      the speciation rate in this clade. For seven other clades, the estimated starting
      dates for their radiation ranges from 7 to 20 Myr ago. Combining the radiation
      patterns for these clades shows that ca. 15% of the modern species evolved during
      the Pleistocene, and almost 40% since the beginning of the Pliocene. We suggest
      that these clades might have radiated in response to the fynbos vegetation
      increasing its extent in the Cape as a result of climatic change.

PMID- 15519978
TI  - Patterns in the assembly of temperate forests around the Northern Hemisphere.
AB  - Recent studies of Northern Hemisphere biogeography have highlighted potentially
      significant differences between disjunction patterns in plants versus animals. To
      assess such differences, we compiled a larger sample of relevant plant
      phylogenies from which disjunction patterns, ancestral areas and directions of
      movement could be inferred. We considered 66 plant clades with species variously
      endemic today to eastern Asia (EA), Europe (including southwestern Asia), eastern
      North America (ENA), and/or western North America (WNA). Within these clades we
      focused on 100 disjunctions among these major areas, for 33 of which absolute
      divergence times have also been inferred. Our analyses uphold the view that
      disjunctions between EA and ENA are exceptionally common in plants, apparently
      more so than in animals. Compared with animals, we find few disjunctions between
      EA and WNA, consistent with increased extinction in WNA or failure of some groups
      to colonize that region. Taken at face value, our data also support the view that
      many temperate forest plant groups originated and diversified within EA, followed
      by movement out of Asia at different times, but mostly during the last 30 Myr.
      This favours Beringia over a North Atlantic land bridge as the primary path
      between the Old World and the New World. Additional studies are needed,
      especially to evaluate the impacts of differential extinction on these patterns,
      to more confidently establish divergence times, and to assess the statistical
      significance of these findings. Fortunately, many more plant groups show relevant
      disjunction patterns and could soon be added to such analyses.

PMID- 15519979
TI  - Environmental causes for plant biodiversity gradients.
AB  - One of the most pervasive patterns observed in biodiversity studies is the
      tendency for species richness to decline towards the poles. One possible
      explanation is that high levels of environmental energy promote higher species
      richness nearer the equator. Energy input may set a limit to the number of
      species that can coexist in an area or alternatively may influence evolutionary
      rates. Within flowering plants (angiosperms), families exposed to a high energy
      load tend to be both more species rich and possess faster evolutionary rates,
      although there is no evidence that one drives the other. Specific environmental
      effects are likely to vary among lineages, reflecting the interaction between
      biological traits and environmental conditions in which they are found. One
      example of this is demonstrated by the high species richness of the iris family
      (Iridaceae) in the Cape of South Africa, a likely product of biological traits
      associated with reproductive isolation and the steep ecological and climatic
      gradients of the region. Within any set of conditions some lineages will tend to
      be favoured over others; however, the identity of these lineages will fluctuate
      with a changing environment, explaining the highly labile nature of
      diversification rates observed among major lineages of flowering plants.

PMID- 15519980
TI  - Organogenic responses of Pinus pinea cotyledons to hormonal treatments: BA
      metabolism and cytokinin content.
AB  - Isolated cotyledons from mature Pinus pinea L. embryos were cultured in vitro in
      a factorial combination of 4.4, 10 and 44.4 microM N6-benzyladenine (BA) for 2,
      4, 8, 16 and 35 days to optimize shoot regeneration. Incubation of explants in
      44.4 microM BA for 4 days, in place of the standard incubation in 4.4 microM BA
      for 35 days, reduced the entire culture period to 4 weeks. Shortening the culture
      period had no significant effect on the caulogenic response or the number of buds
      formed per cotyledon. To establish the relationship between key moments in the
      caulogenic process induced by 4.4 microM BA and the endogenous concentrations of
      the active forms of BA and other isoprenoid-type cytokinins (CKs), we examined
      uptake, metabolism and amount of BA, as well as the amounts of zeatin,
      dihydrozeatin and their ribosides in P. pinea cotyledons after 1, 2, 6, 12 and 24
      h, and 2, 4, 8, 16 and 35 days of exposure to 8-[14C]BA. Uptake and release of BA
      were associated with water movement between explants and the medium during the
      first 8 days of culture. The interconvertible forms of BA were the main
      metabolites formed in the tissues. Inactivation of BA as a result of conjugation
      or oxidation was insignificant. The endogenous concentration of BA + N6
      benzyladenosine was 20-fold higher than the exogenously applied BA during the
      competence acquisition phase (Days 0-3). The concentration of isoprenoid-type CKs
      also increased 16-fold and then decreased during this time. Induction of shoot
      buds (Days 4-8) was characterized by a second peak of BA uptake by explants that
      triggered the synthesis of N6-benzyladenosine-5 -monophosphate and by the
      maintenance of isoprenoid-type CKs. Reestablishment of CK homeostasis marked the
      shift from the induction phase to the shoot development phase in this organogenic
      process (Days 8-12).

PMID- 15519981
TI  - Somatic embryogenesis from vegetative shoot apices of mature trees of Pinus
      patula.
AB  - Embryogenic cultures were initiated and established from apical shoots of mature
      trees of three genotypes of Pinus patula Scheide et Deppe. Factors affecting
      initiation, including cold pretreatment, basal medium composition, growth
      regulators and gelling agent concentration, and the effect of partial desiccation
      on somatic embryo maturation were investigated. Cold pretreatment of thick
      sections (0.5-1.0 mm) of apical shoots at 2 degrees C for 3 days on 0.3%
      activated charcoal induced white mucilaginous embryogenic callus on initiation
      medium. Subculture of this embryogenic callus on maintenance medium resulted in
      the formation of embryonal suspensor masses with proembryos. Partial desiccation
      (12-90 h) of embryogenic tissue at the proembryo stage of development, prior to
      transfer to maturation medium containing 9 g l(-1) Gellan gum, enhanced somatic
      embryo maturation and germinability. The frequency of maturation increased from
      5.3 to 16.5% after 12 h of desiccation and from 16.5 to 73.8% after 24 h of
      desiccation, but longer periods of desiccation were ineffective.

PMID- 15519982
TI  - Carbon budget for Scots pine trees: effects of size, competition and site
      fertility on growth allocation and production.
AB  - Time series of carbon fluxes in individual Scots pine (Pinus sylvestris L.) trees
      were constructed based on biomass measurements and information about component
      specific turnover and respiration rates. Foliage, branch, stem sapwood, heartwood
      and bark components of aboveground biomass were measured in 117 trees sampled
      from 17 stands varying in age, density and site fertility. A subsample of 32
      trees was measured for belowground biomass excluding fine roots. Biomass of fine
      roots was estimated from the results of an earlier study. Statistical models were
      constructed to predict dry mass (DW) of components from tree height and basal
      area, and time derivatives of these models were used to estimate biomass
      increments from height growth and basal area growth. Biomass growth (G) was
      estimated by adding estimated biomass turnover rates to increments, and gross
      photosynthetic production (P) was estimated by adding estimated component
      respiration rates to growth. The method, which predicts the time course of G, P
      and biomass increment in individual trees as functions of height growth and basal
      area growth, was applied to eight example trees representing different dominance
      positions and site fertilities. Estimated G and P of the example trees varied
      with competition, site fertility and tree height, reaching maximum values of 22
      and 43 kg(DW) year(-1), respectively. The site types did not show marked
      differences in productivity of trees of the same height, although height growth
      was greater on the fertile site. The G:P ratio decreased with tree height from 65
      to 45%. Growth allocation to needles and branches increased with increasing
      dominance, whereas growth allocation to the stem decreased. Growth allocation to
      branches decreased and growth allocation to coarse roots increased with
      increasing tree size. Trees at the poor site allocated 49% more to fine roots
      than trees at the fertile site. The belowground parts accounted for 25 to 55% of
      annual G, increasing with tree size and decreasing with site fertility. Annual G
      and P per unit needle mass varied over the ranges 1.9-2.4 and 3.5-4.0 kg(DW) kg(
      1), respectively. The relationship between P and needle mass in the example trees
      was linear and relatively independent of competition, site fertility and age.

PMID- 15519983
TI  - Environmental controls on sap flow in a northern hardwood forest.
AB  - Our objective was to gain a detailed understanding of how photosynthetically
      active radiation (PAR), vapor pressure deficit (D) and soil water interact to
      control transpiration in the dominant canopy species of a mixed hardwood forest
      in northern Lower Michigan. An improved understanding of how these environmental
      factors affect whole-tree water use in unmanaged ecosystems is necessary in
      assessing the consequences of climate change on the terrestrial water cycle. We
      used continuously heated sap flow sensors to measure transpiration in mature
      trees of four species during two successive drought events. The measurements were
      scaled to the stand level for comparison with eddy covariance estimates of
      ecosystem water flux (Fw). Photosynthetically active radiation and D together
      explained 82% of the daytime hourly variation in plot-level transpiration, and
      low soil water content generally resulted in increased stomatal sensitivity to
      increasing D. There were also species-specific responses to drought. Quercus
      rubra L. showed low water use during both dry and wet conditions, and during
      periods of high D. Among the study species, Acer rubrum L. showed the greatest
      degree of stomatal closure in response to low soil water availability. Moderate
      increases in stomatal sensitivity to D during dry periods were observed in
      Populus grandidentata Michx. and Betula papyrifera Marsh. Sap flow scaled to the
      plot level and Fw demonstrated similar temporal patterns of water loss suggesting
      that the mechanisms controlling sap flow of an individual tree also control
      ecosystem evapotranspiration. However, the absolute magnitude of scaled sap flow
      estimates was consistently lower than Fw. We conclude that species-specific
      responses to PAR, D and soil water content are key elements to understanding
      current and future water fluxes in this ecosystem.

PMID- 15519984
TI  - Dependency of branch diameter growth in young Acer trees on light availability
      and shoot elongation.
AB  - Many biomechanical and theoretical studies have been based on the pipe-model
      theory, according to which a tree is regarded as an assemblage of pipes, each
      having the same amount of leaf area or leaf mass. However, the physiological
      mechanisms underlying the theory have not been extensively examined, particularly
      at the branch level. We analyzed how branches and trunks thickened in nine young
      Acer mono Maxim. var. marmoratum (Nichols) Hara f. dissectum (Wesmael) Rehder.
      and A. rufinerve (Siebold & Zucc.) trees. In particular, we examined the roles of
      light, allocation of photosynthates and shoot heterogeneity. The cross-sectional
      area (A) of a branch was proportional to cumulative leaf mass or leaf area of the
      branch, and cumulative cross-sectional area of the daughter branches (SigmaA)
      above a branching point was equal to the A of the mother branch. These results
      indicate the validity of the pipe-model theory. However, the theory was invalid
      for current-year growth of branch cross-sectional area (DeltaA). The
      DeltaA/SigmaDeltaA for a branching point was greatest (nearly equal to 1) at the
      crown surface, decreased with crown depth, and tended to increase again at the
      trunk base, and DeltaA strongly depended on light interception and the yearly
      increment of leaves on the branch. We examined factors that influenced DeltaA
      with multiple regression analysis. The ratio of DeltaA of a branch to branch leaf
      area depended on both relative irradiance and mean current-year shoot length of
      the branch, suggesting that diameter growth of a branch is determined by the
      balance between supply of photosynthates, which depends on light interception by
      the branch, and demand for photosynthates, which is created by the high cambial
      activity associated with vigorous shoot elongation.

PMID- 15519985
TI  - Respiratory responses of Scots pine stems to 5 years of exposure to elevated CO2
      concentration and temperature.
AB  - Stem respiration in 20-year-old Scots pine (Pinus sylvestris L.) trees was
      examined following 5 years of exposure to ambient conditions (CON), elevated
      atmospheric carbon dioxide concentration ([CO2]) (ambient + 350 micromol mol(-1),
      (EC)), elevated temperature (ambient + 2-6 degrees C, (ET)) or a combination of
      elevated [CO2] and elevated temperature (ECT). Stem respiration varied seasonally
      regardless of the treatment and displayed a similar trend to temperature, with
      maximum rates occurring around Day 190 in summer and minimum rates in winter.
      Respiration normalized to 15 degrees C (R15) was higher in the growing season
      than in the non-growing season, whereas the temperature coefficient (Q10) was
      lower in the growing season. Annually averaged R15 was 0.36, 0.43, 0.40 and 0.44
      micromol m(-2) s(-1) under CON, EC, ET and ECT conditions, respectively, whereas
      the corresponding values for total stem respiration were 6.55, 7.69, 7.50 and
      7.90 mol m(-2) year(-1). The EC, ET and ECT treatments increased R15 by 18, 11
      and 22%, respectively, relative to CON, and increased the modeled annual total
      stem respiration by 18, 15 and 21%. The increase in modeled annual stem
      respiration under EC and ECT conditions was caused mainly by higher maintenance
      respiration (22 and 25%, respectively, whereas the increase in growth respiration
      was 9 and 12%). Growth respiration was unaltered by ET. The treatments did not
      significantly affect the respiratory response to stem temperature; the mean Q10
      value was 2.04, 2.10, 1.99 and 2.12 in the CON, EC, ET and ECT treatments,
      respectively. It is suggested that the increase in stem respiration was partly a
      result of the increased growth rate. We conclude that elevated [CO2] increased
      the maintenance component of respiration more than the growth component.

PMID- 15519986
TI  - Forest thinning and soil respiration in a ponderosa pine plantation in the Sierra
      Nevada.
AB  - Soil respiration is controlled by soil temperature, soil water, fine roots,
      microbial activity, and soil physical and chemical properties. Forest thinning
      changes soil temperature, soil water content, and root density and activity, and
      thus changes soil respiration. We measured soil respiration monthly and soil
      temperature and volumetric soil water continuously in a young ponderosa pine
      (Pinus ponderosa Dougl. ex P. Laws. & C. Laws.) plantation in the Sierra Nevada
      Mountains in California from June 1998 to May 2000 (before a thinning that
      removed 30% of the biomass), and from May to December 2001 (after thinning).
      Thinning increased the spatial homogeneity of soil temperature and respiration.
      We conducted a multivariate analysis with two independent variables of soil
      temperature and water and a categorical variable representing the thinning event
      to simulate soil respiration and assess the effect of thinning. Thinning did not
      change the sensitivity of soil respiration to temperature or to water, but
      decreased total soil respiration by 13% at a given temperature and water content.
      This decrease in soil respiration was likely associated with the decrease in root
      density after thinning. With a model driven by continuous soil temperature and
      water time series, we estimated that total soil respiration was 948, 949 and 831
      g C m(-2) year(-1) in the years 1999, 2000 and 2001, respectively. Although
      thinning reduced soil respiration at a given temperature and water content,
      because of natural climate variability and the thinning effect on soil
      temperature and water, actual cumulative soil respiration showed no clear trend
      following thinning. We conclude that the effect of forest thinning on soil
      respiration is the combined result of a decrease in root respiration, an increase
      in soil organic matter, and changes in soil temperature and water due to both
      thinning and interannual climate variability.

PMID- 15519987
TI  - Assessing forest structure and function from spectral transmittance measurements:
      a case study in a Mediterranean holm oak forest.
AB  - Annual changes in structural attributes and seasonal dynamics in water content,
      photosynthetic rate and light-use efficiency (LUE) were assessed by spectral
      transmittance for 4 years (1999-2003) in six stands of a Mediterranean holm oak
      forest. Green biomass, total biomass and leaf area index (LAI) were determined.
      In 1999, seasonal dynamics of net carbon dioxide (CO2) exchange and water content
      were measured. We recorded photosynthetically active radiation (PAR)
      transmittance and hyperspectral transmittance in the 400-1100 nm region and
      derived reflectance-based vegetation indices. Transmittance over the PAR region
      derived from either ceptometer or spectroradiometer measurements (PART and TPAR,
      respectively) was related to green and total biomass. Both PART and TPAR were
      also related to LAI (r=0.79 and r=0.70, respectively, P <0.001) and were
      appropriate for comparison among stands, whereas subtle changes in LAI within a
      stand were better assessed by the transmittance amplitude in the red edge region
      (TRE) (within a stand, r=0.77-0.99, P <0.001). Spectral transmittance-based
      indices successfully captured physiological processes that occurred on temporal
      (seasonal) and spatial scales. The transmittance-based water index (TWI) was
      related to both foliage and canopy water content (r=0.69, P <0.001). Estimates of
      foliage and canopy water content improved in dense (closed) stands (r=0.84 and
      r=0.87, respectively, P <0.001) compared with low-density stands. Under non
      drought conditions, transmittance-based photochemical reflectance index (TPRI)
      was related to LUE (r=0.58, P <0.05) and net CO2 exchange (r=0.72, P <0.01), and
      the combined TPAR x TPRI index greatly improved these relationships (r=0.93 and
      r=0.84, respectively, P <0.01), indicating that both structural and physiological
      adjustments modified CO2 fixation capacity in these forest stands. Our novel
      approach to the study of transmitted radiation provides a tool for estimating
      structural and functional variables such as LAI, LUE and water content, which are
      key determinants of terrestrial productivity.

PMID- 15519988
TI  - Scots pine responses to elevated temperature and carbon dioxide concentration:
      growth and wood properties.
AB  - Growth and wood properties of 20-year-old Scots pine (Pinus sylvestris L.) trees
      were studied for 6 years in 16 closed chambers providing a factorial combination
      of two temperature regimes (ambient and elevated) and two carbon dioxide
      concentrations ([CO2]) (ambient and twice ambient). The elevation of temperature
      corresponded to the predicted effect at the site of a doubling in atmospheric
      [CO2]. Annual height and radial growth and wood properties were analyzed during
      1997-2002. Physical wood properties analyzed included early- and latewood widths
      and their proportions, intra-ring wood densities, early- and latewood density and
      mean fiber length. Chemical wood properties analyzed included concentrations of
      acetone-soluble extractives, lignin, cellulose and hemicellulose. There were no
      significant treatment effects on height growth during the 6-year study. Elevated
      [CO2] increased ring width by 66 and 47% at ambient and elevated temperatures,
      respectively. At ambient [CO2], elevated temperature increased ring width by 19%.
      Increased ring width in response to elevated [CO2] resulted from increases in
      both early- and latewood width; however, there was no effect of the treatments on
      early- and latewood proportions. Mean wood density, earlywood density and fiber
      length increased in response to elevated temperature. The chemical composition of
      wood was affected by elevated [CO2], which reduced the cellulose concentration,
      and by elevated temperature, which reduced the concentration of acetone-soluble
      extractives. Thus, over the 6-year period, radial growth was significantly
      increased by elevated [CO2], and some wood properties were significantly affected
      by elevated temperature or elevated [CO2], or both, indicating that climate
      change may affect the material properties of wood.

PMID- 15519989
TI  - Element accumulation patterns of deciduous and evergreen tree seedlings on acid
      soils: implications for sensitivity to manganese toxicity.
AB  - Foliar nutrient imbalances, including the hyperaccumulation of manganese (Mn),
      are correlated with symptoms of declining health in sensitive tree species
      growing on acidic forest soils. The objectives of this study were to: (1) compare
      foliar nutrient accumulation patterns of six deciduous (sugar maple (Acer
      saccharum Marsh.), red maple (Acer rubrum L.), red oak (Quercus rubra L.), white
      oak (Quercus alba L.), black cherry (Prunus serotina Ehrh.) and white ash
      (Fraxinus americana L.)) and three evergreen (eastern hemlock (Tsuga canadensis
      L.), white pine (Pinus strobus L.) and white spruce (Picea glauca (Moench)
      Voss.)) tree species growing on acidic forest soils; and (2) examine how leaf
      phenology and other traits that distinguish evergreen and deciduous tree species
      influence foliar Mn accumulation rates and sensitivity to excess Mn. For the
      first objective, leaf samples of seedlings from five acidic, non-glaciated field
      sites on Pennsylvania's Allegheny Plateau were collected and analyzed for leaf
      element concentrations. In a second study, we examined growth and photosynthetic
      responses of seedlings exposed to excess Mn in sand culture. In field samples, Mn
      in deciduous foliage hyperaccumulated to concentrations more than twice as high
      as those found in evergreen needles. Among species, sugar maple was the most
      sensitive to excess Mn based on growth and photosynthetic measurements.
      Photosynthesis in red maple and red oak was also sensitive to excess Mn, whereas
      white oak, black cherry, white ash and the three evergreen species were tolerant
      of excess Mn. Among the nine species, relative rates of photosynthesis were
      negatively correlated with foliar Mn concentrations, suggesting that
      photosynthetic sensitivity to Mn is a function of its rate of accumulation in
      seedling foliage.

PMID- 15519990
TI  - Seasonal variation in biomass and carbohydrate partitioning of understory sugar
      maple (Acer saccharum) and yellow birch (Betula alleghaniensis) seedlings.
AB  - We investigated seasonal patterns of biomass and carbohydrate partitioning in
      relation to shoot growth phenology in two age classes of sugar maple (Acer
      saccharum Marsh.) and yellow birch (Betula alleghaniensis Britt.) seedlings
      growing in the understory of a partially harvested forest. The high root:shoot
      biomass ratio and carbohydrate concentration of sugar maple are characteristic of
      species with truncated growth patterns (i.e., cessation of aboveground shoot
      growth early in the growing season), a conservative growth strategy and high
      shade tolerance. The low root:shoot biomass ratio and carbohydrate concentration
      of yellow birch are characteristic of species with continuous growth patterns, an
      opportunistic growth strategy and low shade tolerance. In both species, starch
      represented up to 95% of total nonstructural carbohydrates and was mainly found
      in the roots. Contrary to our hypothesis, interspecific differences in shoot
      growth phenology (i.e., continuous versus truncated) did not result in
      differences in seasonal patterns of carbohydrate partitioning. Our results help
      explain the niche differentiation between sugar maple and yellow birch in
      temperate, deciduous understory forests.

PMID- 15519991
TI  - Effects of seed origin and sowing time on timing of height growth cessation of
      Betula pendula seedlings.
AB  - We studied the effects of seed origin and sowing time on height development and
      timing of height growth cessation of first-year silver birch (Betula pendula
      Roth) seedlings in a greenhouse experiment. Seeds of seven origins ranging in
      latitudes from 58 degrees to 67 degrees N were sown at 1-2-week intervals eight
      times from May 21 to July 30, 2001. The day/night temperature in the greenhouse
      was set at 20/10 degrees C, but lighting was natural and day length varied
      accordingly. Seedling height was measured twice a week. The interaction term
      between seed origin and sowing date was significant, but the pattern of height
      development and timing of growth cessation depended systematically on latitude of
      seed origin and sowing date. As seed origin became increasingly northern, growth
      cessation began earlier and resulted in shorter growth periods. Later sowing
      dates delayed growth cessation but also shortened the growth period. Final
      seedling height systematically decreased with increasingly northern origins and
      with later sowings. Linear regression analysis predicted timing of growth
      cessation, night length at growth cessation, length of growth period and final
      seedling height with high precision when the latitude of seed origin and sowing
      time were predictor variables. The timing of height growth cessation was
      determined by the seed origin, night length and developmental stage of the
      seedlings.

PMID- 15519992
TI  - Low temperature, but not photoperiod, controls growth cessation and dormancy
      induction and release in apple and pear.
AB  - In contrast to most temperate woody species, apple and pear and some other woody
      species of the Rosaceae family are insensitive to photoperiod, and no alternative
      environmental seasonal signal is known to control their dormancy. We studied
      growth and dormancy induction in micropropagated plants of four apple (Malus
      pumila Mill.) and one pear (Pyrus communis L.) commercial rootstock cultivars in
      controlled environments. The results confirm that growth cessation and dormancy
      induction in apple and pear are not influenced by photoperiod, and demonstrate
      that low temperature (< 12 degrees C) consistently induces both processes,
      regardless of photoperiodic conditions. Successive stages of the autumn syndrome
      (growth cessation, formation of bud scales and winter buds, leaf senescence and
      abscission, and dormancy induction) occurred in response to low temperature. Long
      days increased internode length at higher temperatures, but had no significant
      effect on leaf production in any of the cultivars. Chilling at 6 or 9 degrees C
      for at least 6 weeks (about 1000 h) was required for dormancy release and growth
      resumption, whereas treatment at 12 degrees C was marginally effective, even
      after 14 weeks of exposure. We are thus faced with the paradox that the same low
      temperature conditions that induce dormancy are also required for dormancy
      release in these species.

PMID- 15519993
TI  - Effects of soil temperature on shoot and root growth and nutrient uptake of 5
      year-old Norway spruce seedlings.
AB  - Soil temperature is a main factor limiting root growth in the boreal forest. To
      simulate the possible soil-warming effect of future climate change, 5-year-old
      Norway spruce (Picea abies (L.) Karst.) seedlings were subjected to three
      simulated growing seasons in controlled environment rooms. The seedlings were
      acclimated to a soil temperature of 16 degrees C during the first (GS I) and
      third growing seasons (GS III), but were assigned to random soil-temperature
      treatments of 9, 13, 18 and 21 degrees C during the second growing season (GS
      II). In GS II, shoot diameter growth was lowest in the 21 degrees C treatment and
      root growth was lowest in the 9 degrees C treatment. In GS III, shoot height and
      root length growth improved in seedlings that had been kept at 9 degrees C during
      GS II, indicating compensatory growth in response to increased soil temperature.
      The temporary decrease in soil temperature had no long-lasting significant effect
      on seedling biomass or total nutrient uptake. At the end of GS III, fine roots of
      seedlings exposed to a soil temperature of 21 degrees C in GS II were distributed
      more evenly between the organic and mineral soil layers than roots of seedlings
      in the other treatments. During GS II and GS III, root growth started earlier
      than shoot growth, decreased during the rapid shoot elongation phase and
      increased again as shoot growth decreased.

PMID- 15519994
TI  - Light sources with different spectra affect root and mycorrhiza formation in
      Scots pine in vitro.
AB  - We studied the effects of broad-spectrum light quality on the interaction between
      the ectomycorrhizal fungus Pisolithus tinctorius (Pers.) Coker and Couch and
      Scots pine (Pinus sylvestris L.) seedlings and hypocotyl cuttings cultured in
      vitro. The light sources were cool white (CW), warm white (WW) and red-rich
      daylight (RD) fluorescent lamps. Inoculation with P. tinctorius enhanced
      adventitious root formation of the cuttings in all light treatments. Rooting of
      the inoculated cuttings was highest in WW light (89%), followed by CW (73%) and
      RD light (66%). During 6 weeks of in vitro culture, rooted cuttings formed only a
      few lateral roots. The fungus grew over lateral roots, but the Hartig net was
      absent in all light treatments. In non-inoculated cuttings, neither root
      formation nor subsequent root growth was affected by light quality. In the
      seedling experiment, inoculation in the WW treatment resulted in a significantly
      (P < 0.05) greater number of lateral roots than inoculation in the RD treatment.
      The percentage of lateral roots covered with fungal hyphae was also highest in WW
      light (62%), followed by CW (50%) and RD (27%) light. A similar pattern was
      observed in the intensity of Hartig net formation. We conclude that effects of
      broad-spectrum light quality on the ectomycorrhizal fungus-root interaction are
      dependent on the developmental stage of the root.

PMID- 15519995
TI  - Mutational analysis of the alpha-1 repeat of the cardiac Na(+)-Ca2+ exchanger.
AB  - The Na(+)-Ca2+ exchanger contains internal regions of sequence homology known as
      the alpha repeats. The first region (alpha-1 repeat) includes parts of
      transmembrane segments (TMSs) 2 and 3 and a linker modeled to be a reentrant
      loop. To determine the involvement of the reentrant loop and TMS 3 portions of
      the alpha-1 repeat in exchanger function, we generated a series of mutants and
      examined ion binding and transport and regulatory properties. Mutations in the
      reentrant loop did not substantially modify transport properties of the exchanger
      though the Hill coefficient for Na+ and the rate of Na(+)-dependent inactivation
      were decreased. Mutations in TMS 3 had more striking effects on exchanger
      activity. Of mutations at 10 positions, 3 behaved like the wild-type exchanger
      (V137C, A141C, M144C). Mutants at two other positions expressed no activity
      (Ser139) or very low activity (Gly138). Six different mutations were made at
      position 143; only N143D was active, and it displayed wild-type characteristics.
      The highly specific requirement for an asparagine or aspartate residue at this
      position may indicate a key role for Asn143 in the transport mechanism. Mutations
      at residues Ala140 and Ile147 decreased affinity for intracellular Na+, whereas
      mutations at Phe145 increased Na+ affinity. The cooperativity of Na+ binding was
      also altered. In no case was Ca2+ affinity changed. TMS 3 may form part of a site
      that binds Na+ but not Ca2+. We conclude that TMS 3 is involved in Na+ binding
      and transport, but previously proposed roles for the reentrant loop need to be
      reevaluated.

PMID- 15519996
TI  - Differential regulation of G protein alpha subunit trafficking by mono- and
      polyubiquitination.
AB  - Previously we used mass spectrometry to show that the yeast G protein alpha
      subunit Gpa1 is ubiquitinated at Lys-165, located within a subdomain not present
      in other G alpha proteins (Marotti, L. A., Jr., Newitt, R., Wang, Y., Aebersold,
      R., and Dohlman, H. G. (2002) Biochemistry 41, 5067-5074). Here we describe the
      functional role of Gpa1 ubiquitination. We find that Gpa1 expression is elevated
      in mutants deficient in either proteasomal or vacuolar protease function.
      Vacuolar protease pep4 mutants accumulate monoubiquitinated Gpa1, and much of the
      protein is localized within the vacuolar compartment. In contrast, proteasome
      defective rpt6/cim3 mutants accumulate polyubiquitinated Gpa1, and in this case
      the protein exhibits cytoplasmic localization. Cells that lack Ubp12 ubiquitin
      processing protease activity accumulate both mono- and polyubiquitinated forms of
      Gpa1. In this case, Gpa1 accumulates in both the cytoplasm and vacuole. Finally,
      a Gpa1 mutant that lacks the ubiquitinated subdomain remains unmodified and is
      predominantly localized at the plasma membrane. These data reveal a strong
      relationship between the extent of ubiquitination and trafficking of the G
      protein alpha subunit to its site of degradation.

PMID- 15519998
TI  - Double-stranded RNAs from the helminth parasite Schistosoma activate TLR3 in
      dendritic cells.
AB  - Stimulation of dendritic cells (DCs) by the egg stage of the helminth parasite
      Schistosoma mansoni activates a signaling pathway resulting in type I interferon
      (IFN) and IFN-stimulated gene (ISG) expression. Here, we demonstrate that S.
      mansoni eggs disjointedly activate myeloid differentiation factor 88 (MyD88)
      dependent and MyD88-independent pathways in DCs. Inflammatory cytokine expression
      and NF-kappa B activation in DCs from MyD88-deficient mice were impaired, whereas
      signaling transducer activator of transcription (STAT) 1(Tyr701) phosphorylation
      and ISG expression were intact in MyD88 or Toll-like receptor (TLR)4-deficient
      counterparts. Accordingly, we analyzed distinct TLR members for their ability to
      respond to schistosome eggs and established that TLR3 resulted in the activation
      of NF-kappa B and the positive regulatory domain III-I site from IFN-beta
      promoter. Unexpectedly, egg-derived RNA possessed RNase A-resistant and RNase III
      sensitive structures capable of triggering TLR3 activation, suggesting the
      involvement of double-stranded (ds) structures. Moreover, DCs from TLR3-deficient
      mice displayed a complete loss of signaling transducer activator of transcription
      1 phosphorylation and ISG expression in response to egg-derived dsRNA. Finally,
      TLR3-deficient DCs showed a reduced response to schistosome eggs relative to wild
      type cells. Collectively, our data suggest for the first time that dsRNA from a
      non-viral pathogen may act as an inducer of the innate immune system through
      TLR3.

PMID- 15519997
TI  - Mnt1p and Mnt2p of Candida albicans are partially redundant alpha-1,2
      mannosyltransferases that participate in O-linked mannosylation and are required
      for adhesion and virulence.
AB  - The MNT1 gene of the human fungal pathogen Candida albicans is involved in O
      glycosylation of cell wall and secreted proteins and is important for adherence
      of C. albicans to host surfaces and for virulence. Here we describe the molecular
      analysis of CaMNT2, a second member of the MNT1-like gene family in C. albicans.
      Mnt2p also functions in O-glycosylation. Mnt1p and Mnt2p encode partially
      redundant alpha-1,2-mannosyltransferases that catalyze the addition of the second
      and third mannose residues in an O-linked mannose pentamer. Deletion of both
      copies of MNT1 and MNT2 resulted in reduction in the level of in vitro
      mannosyltransferase activity and truncation of O-mannan. Both the mnt2Delta and
      mnt1Delta single mutants were significantly reduced in adherence to human buccal
      epithelial cells and Matrigel-coated surfaces, indicating a role for O
      glycosylated cell wall proteins or O-mannan itself in adhesion to host surfaces.
      The double mnt1Deltamnt2Delta mutant formed aggregates of cells that appeared to
      be the result of abnormal cell separation. The double mutant was attenuated in
      virulence, underlining the importance of O-glycosylation in pathogenesis of C.
      albicans infections.

PMID- 15519999
TI  - EVI1 abrogates interferon-alpha response by selectively blocking PML induction.
AB  - EVI1 is an oncogene frequently associated with chronic and acute myeloid
      leukemia. In hematopoietic cells, EVI1 impairs several pathways including
      proliferation, differentiation, and apoptosis. Interferon-alpha (IFN-alpha) is a
      powerful cytokine that controls the immune response and limits the expansion of
      several tissues including bone marrow. These properties contribute to the
      effectiveness of IFN-alpha in the treatment of many neoplastic disorders
      especially chronic myeloid leukemia. We report here that in murine hematopoietic
      progenitors the expression of EVI1 completely abrogates the antiproliferative and
      apoptotic effects of IFN-alpha. EVI1 does not repress the JAK/STAT signaling
      pathway or the activation of many IFN-responsive genes. On the contrary, EVI1
      prolongs the phosphorylation of STAT1 and the activation of an IFN-dependent
      reporter gene. However, EVI1 specifically represses the IFN-dependent induction
      of the tumor suppressor PML and blocks the apoptotic pathways activated by PML.
      We show that the position of the ISRE, which is located within the first exon of
      PML, is critical to block PML induction by IFN-alpha. The relocation of the ISRE
      to a position upstream of the transcription start site is sufficient to re
      establish the response to IFN in the presence of EVI1. Our data suggest that
      stabilized STAT1 phosphorylation and prolonged binding of the STAT1 complex to
      the first exon could impair PML transcription and inhibit the activation of PML
      dependent apoptotic pathways resulting in loss of IFN response. These results
      point to a novel mechanism utilized by an oncogene to escape normal cell response
      to growth-controlling cytokines.

PMID- 15520000
TI  - The structure of RalF, an ADP-ribosylation factor guanine nucleotide exchange
      factor from Legionella pneumophila, reveals the presence of a cap over the active
      site.
AB  - The Legionella pneumophila protein RalF is secreted into host cytosol via the
      Dot/Icm type IV transporter where it acts to recruit ADP-ribosylation factor
      (Arf) to pathogen-containing phagosomes in the establishment of a replicative
      organelle. The presence in RalF of the Sec7 domain, present in all Arf guanine
      nucleotide exchange factors, has suggested that recruitment of Arf is an early
      step in pathogenesis. We have determined the crystal structure of RalF and of the
      isolated Sec7 domain and found that RalF is made up of two domains. The Sec7
      domain is homologous to mammalian Sec7 domains. The C-terminal domain forms a cap
      over the active site in the Sec7 domain and contains a conserved folding motif,
      previously observed in adaptor subunits of vesicle coat complexes. The importance
      of the capping domain and of the glutamate in the "glutamic finger," conserved in
      all Sec7 domains, to RalF functions was examined using three different assays.
      These data highlight the functional importance of domains other than Sec7 in Arf
      guanine nucleotide exchange factors to biological activities and suggest novel
      mechanisms of regulation of those activities.

PMID- 15520002
TI  - Novel mechanism of interaction of p85 subunit of phosphatidylinositol 3-kinase
      and ErbB3 receptor-derived phosphotyrosyl peptides.
AB  - Ligand-activated and tyrosine-phosphorylated ErbB3 receptor binds to the SH2
      domain of the p85 subunit of phosphatidylinositol 3-kinase and initiates
      intracellular signaling. Here, we studied the interactions between the N- (N-SH2)
      and C- (C-SH2) terminal SH2 domains of the p85 subunit of the
      phosphatidylinositol 3-kinase and eight ErbB3 receptor-derived phosphotyrosyl
      peptides (P-peptides) by using molecular dynamics, free energy, and surface
      plasmon resonance (SPR) analyses. In SPR analysis, these P-peptides showed no
      binding to the C-SH2 domain, but P-peptides containing a phospho-YXXM or a non
      phospho-YXXM motif did bind to the N-SH2 domain. The N-SH2 domain has two
      phosphotyrosine binding sites in its N- (N1) and C- (N2) terminal regions.
      Interestingly, we found that P-peptides of pY1180 and pY1241 favored to bind to
      the N2 site, although all other P-peptides showed favorable binding to the N1
      site. Remarkably, two phosphotyrosines, pY1178 and pY1243, which are just 63
      amino acids apart from the pY1241 and pY1180, respectively, showed favorable
      binding to the N1 site. These findings indicate a possibility that the pair of
      phosphotyrosines, pY1178-pY1241 or pY1243-pY1180, will fold into an appropriate
      configuration for binding to the N1 and N2 sites simultaneously. Our model
      structures of the cytoplasmic C-terminal domain of ErbB3 receptor also strongly
      supported the speculation. The calculated binding free energies between the N-SH2
      domain and P-peptides showed excellent qualitative agreement with SPR data with a
      correlation coefficient of 0.91. The total electrostatic solvation energy between
      the N-SH2 domain and P-peptide was the dominant factor for its binding affinity.

PMID- 15520001
TI  - Excess mannose limits the growth of phosphomannose isomerase PMI40 deletion
      strain of Saccharomyces cerevisiae.
AB  - Phosphomannose isomerase (PMI40) catalyzes the conversion between fructose 6
      phosphate and mannose 6-phosphate and thus connects glycolysis, i.e. energy
      production and GDP-mannose biosynthesis or cell wall synthesis in Saccharomyces
      cerevisiae. After PMI40 deletion (pmi(-)) the cells were viable only if fed with
      extracellular mannose and glucose. In an attempt to force the GDP-mannose
      synthesis in the pmi(-) strain by increasing the extracellular mannose
      concentrations, the cells showed significantly reduced growth rates without any
      alterations in the intracellular GDP-mannose levels. To reveal the mechanisms
      resulting in reduced growth rates, we measured genome-wide gene expression
      levels, several metabolite concentrations, and selected in vitro enzyme
      activities in central metabolic pathways. The increasing of the initial mannose
      concentration led to an increase in the mannose 6-phosphate concentration, which
      inhibited the activity of the second enzyme in glycolysis, i.e. phosphoglucose
      isomerase converting glucose 6-phosphate to fructose 6-phosphate. As a result of
      this limitation, the flux through glycolysis was decreased as was the median
      expression of the genes involved in glycolysis. The expression levels of RAP1, a
      transcription factor involved in the regulation of the mRNA levels of several
      enzymes in glycolysis, as well as those of cell cycle regulators CDC28 and CLN3,
      decreased concomitantly with the growth rates and expression of many genes
      encoding for enzymes in glycolysis.

PMID- 15520003
TI  - Characterization of the iron-sulfur cluster N7 (N1c) in the subunit NuoG of the
      proton-translocating NADH-quinone oxidoreductase from Escherichia coli.
AB  - The proton-pumping NADH-quinone oxidoreductase from Escherichia coli houses nine
      iron-sulfur clusters, eight of which are found in its mitochondrial counterpart,
      complex I. The extra putative iron-sulfur cluster binding site with a
      CXXCXXXCX(27)C motif in the NuoG subunit has been assigned to ligate a [2Fe-2S]
      (N1c). However, we have shown previously that the Thermus thermophilus N1c
      fragment containing this motif ligates a [4Fe-4S] (Nakamaru-Ogiso, E., Yano, T.,
      Ohnishi, T., and Yagi, T. (2002) J. Biol. Chem. 277, 1680-1688). In the current
      study, we individually inactivated four sets of the iron-sulfur binding motifs in
      the E. coli NuoG subunit by replacing all four ligands with Ala. Each mutant
      subunit, designated Delta N1b, Delta N1c, Delta N4, and Delta N5, was expressed
      as maltose-binding protein fusion proteins. After in vitro reconstitution, all
      mutant subunits were characterized by EPR. Although EPR signals from cluster N1b
      were not detected in any preparations, we detected two [4Fe-4S] EPR signals with
      g values of g(x,y,z) = 1.89, 1.94, and 2.06, and g(x,y,z) = 1.91, 1.94, and 2.05
      at 6-20 K in wild type, Delta N1b, and Delta N5. The former signal was assigned
      to cluster N4, and the latter signal was assigned to cluster N1c because of their
      disappearance in Delta N4 and Delta N1c. Confirming that a [4Fe-4S] cluster
      ligates to the N1c motif, we propose to replace its misleading [2Fe-2S] name,
      N1c, with "cluster N7." In addition, because these mutations differently affected
      the assembly of peripheral subunits by in trans complementation analysis with the
      nuoG knock-out strain, the implicated structural importance of the iron-sulfur
      binding domains is discussed.

PMID- 15520004
TI  - Distinct molecular mechanisms for agonist peptide binding to types A and B
      cholecystokinin receptors demonstrated using fluorescence spectroscopy.
AB  - Fluorescence spectroscopy provides a direct method for evaluating the environment
      of a fluorescent ligand bound to its receptor. We utilized this methodology to
      determine the environment of Alexa within a cholecystokinin (CCK)-like probe
      (Alexa488-Gly-[(Nle(28,31))CCK-26-33]; CCK-8 probe) bound to the type A CCK
      receptor (Harikumar, K. G., Pinon, D. L., Wessels, W. S., Prendergast, F. G., and
      Miller, L. J. (2002) J. Biol. Chem. 277, 18552-18560). Here, we study this probe
      at the type B CCK receptor and develop another probe with its fluorophore closer
      to the carboxyl-terminal pharmacophore of type B receptor ligands (Alexa488-Trp
      Nle-Asp-Phe-NH2; CCK-4 probe). Both probes bound to type B CCK receptors in a
      saturable and specific manner and represented full agonists. Similar to the type
      A receptor, at the type B receptor these probes exhibited shorter lifetimes and
      lower anisotropy when the receptor was in the active conformation than when it
      was shifted to its inactive, G protein-uncoupled state using guanosine 5'
      [beta,gamma-imido]-triphosphate trisodium salt. Absolute values for lifetime and
      anisotropy were lower for the CCK-8 probe bound to the type B receptor than for
      this probe bound to the type A receptor, and Alexa fluorescence was more easily
      quenched by iodide at the type B receptor. This represents the first direct
      evidence that, despite having identical affinities for binding and potencies for
      activating type A and B receptors, CCK is docked via distinct mechanisms, with
      the amino terminus more exposed to the aqueous milieu when bound to the type B
      CCK receptor than to the type A CCK receptor. Of interest, despite this
      difference in binding, activation of both receptors results in analogous
      direction of movement of the fluorescent indicator probes.

PMID- 15520005
TI  - The key role of protein flexibility in modulating IgE interactions.
AB  - The interaction between IgE and its high affinity receptor (FcepsilonRI) is a
      critical step in the development of allergic responses. Detailed characterization
      of the IgE-FcepsilonRI interaction may offer insights into possible modes of
      inhibiting the interaction, which could thereby act as a potential therapy for
      allergy. In this study, NMR, CD, and fluorescence spectroscopies have been used
      to characterize structurally the Cepsilon3 domain of IgE and its interaction with
      other protein ligands, namely, Cepsilon2, Cepsilon4, sFcepsilonRIalpha, and CD23.
      We have shown that the recombinant Cepsilon3 domain exists alone in solution as a
      "molten globule." On interaction with sFcepsilonRIalpha, Cepsilon3 adopts a
      folded tertiary structure, as shown by the release of the fluorescent probe 8
      anilinonaphthalene-1-sulfonate and by characteristic changes in the (1)H, (15)N
      heteronuclear single quantum coherence NMR spectrum. However, the interactions
      between the Cepsilon3 domain and Cepsilon2, Cepsilon4, or CD23 do not induce such
      folding and would therefore be expected to involve only local interaction
      surfaces. The conformational flexibility of the Cepsilon3 domain of the whole IgE
      molecule may play a role in allowing fine tuning of the affinity and specificity
      of IgE for a variety of different physiological ligands and may be involved in
      the conformational change of IgE postulated to occur on interaction with
      FcepsilonRI.

PMID- 15520006
TI  - RGS14 is a centrosomal and nuclear cytoplasmic shuttling protein that traffics to
      promyelocytic leukemia nuclear bodies following heat shock.
AB  - RGS14, a member of the regulator of G-protein signaling (RGS) protein family,
      possesses an N-terminal RGS domain, two Raf-like Ras-binding domains, and a
      GoLoco motif, which has GDP dissociation inhibitor activity. In this study we
      show that unique among the known mammalian RGS proteins, RGS14 localizes in
      centrosomes. Its first Ras-binding domain is sufficient to target RGS14 to
      centrosomes. RGS14 also shuttles between the cytoplasm and nucleus, and its
      nuclear export depends on the CRM-1 nuclear export receptor. Mutation of a
      nuclear export signal or treatment with leptomycin B causes nuclear accumulation
      of RGS14 and its association with promyelocytic leukemia protein nuclear bodies.
      Furthermore, a point mutant defective in nuclear export fails to target to
      centrosomes, suggesting that nuclear cytoplasmic shuttling is necessary for its
      proper localization. Mild heat stress, but not proteotoxic or transcription
      linked stresses, re-localizes the RGS14 from the cytoplasm to promyelocytic
      leukemia nuclear bodies. Expression of RGS14, but not point mutants that disrupt
      the functional activity of its RGS domain or GoLoco motif, enhances the reporter
      gene activity. The multifunctional domains and the dynamic subcellular
      localization of RGS14 implicate it in a diverse set of cellular processes
      including centrosome and nuclear functions and stress-induced signaling pathways.

PMID- 15520007
TI  - Methylglyoxal, a metabolite derived from glycolysis, functions as a signal
      initiator of the high osmolarity glycerol-mitogen-activated protein kinase
      cascade and calcineurin/Crz1-mediated pathway in Saccharomyces cerevisiae.
AB  - Methylglyoxal (MG) is a typical 2-oxoaldehyde derived from glycolysis, although
      it inhibits the growth of cells in all types of organism. Hence, it has been
      questioned why such a toxic metabolite is synthesized via the ubiquitous energy
      generating pathway. We have previously reported that expression of GLO1, coding
      for the major enzyme detoxifying MG, was induced by osmotic stress in a high
      osmolarity glycerol (HOG)-mitogen-activated protein (MAP) kinase-dependent manner
      in Saccharomyces cerevisiae. Here we show that MG activates the HOG-MAP kinase
      cascade. Two osmosensors, Sln1 and Sho1, have been identified to function
      upstream of the HOG-MAP kinase cascade, and we reveal that MG initiates the
      signal transduction to this MAP kinase cascade through the Sln1 branch. We also
      demonstrate that MG activates the Msn2 transcription factor. Moreover, MG
      activated the uptake of Ca(2+) in yeast cells, thereby stimulating the
      calcineurin/Crz1-mediated Ca(2+) signaling pathway. We propose that MG functions
      as a signal initiator in yeast.

PMID- 15520008
TI  - Prostaglandin E2 regulates the complement inhibitor CD55/decay-accelerating
      factor in colorectal cancer.
AB  - Cyclooxygenase-derived prostaglandin E(2) (PGE(2)) stimulates tumor progression
      by modulating several proneoplastic pathways. The mechanisms by which PGE(2)
      promotes tumor growth and metastasis through stimulation of cell migration,
      invasion, and angiogenesis have been fairly well characterized. Much less is
      known, however, about the molecular mechanisms responsible for the
      immunosuppressive effects of PGE(2). We identified PGE(2) target genes and
      subsequently studied their biologic role in colorectal cancer cells. The
      complement regulatory protein decay-accelerating factor (DAF or CD55) was induced
      following PGE(2) treatment of LS174T colon cancer cells. Analysis of PGE(2)
      mediated activation of the DAF promoter employing 5'-deletion luciferase
      constructs suggests that regulation occurs at the transcriptional level via a
      cyclic AMP/protein kinase A-dependent pathway. Nonsteroidal anti-inflammatory
      drugs blocked DAF expression in HCA-7 colon cancer cells, which could be restored
      by the addition of exogenous PGE(2). Finally, we observed an increase in DAF
      expression in the intestinal mucosa of Apc(Min+/-) mice treated with PGE(2) in
      vivo. In summary, these results indicate a novel immunosuppressive role for
      PGE(2) in the development of colorectal carcinomas.

PMID- 15520009
TI  - Alpha-conotoxin BuIA, a novel peptide from Conus bullatus, distinguishes among
      neuronal nicotinic acetylcholine receptors.
AB  - Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion
      channels. Alpha subunits, together with beta 2 and/or beta 4 subunits, form
      ligand-binding sites at alpha/beta subunit interfaces. Predatory marine snails of
      the genus Conus are a rich source of nAChR-targeted peptides. Using conserved
      features of the alpha-conotoxin signal sequence and 3'-untranslated sequence
      region, we have cloned a novel gene from the fish-eating snail, Conus bullatus;
      the gene codes for a previously unreported alpha-conotoxin with unusual 4/4
      spacing of amino acids in the two disulfide loops. Chemical synthesis of the
      predicted mature toxin was performed. The resulting peptide, alpha-conotoxin
      BuIA, was tested on cloned nAChRs expressed in Xenopus oocytes. The peptide
      potently blocks numerous rat nAChR subtypes, with highest potency for alpha 3-
      and chimeric alpha 6-containing nAChRs; BuIA blocks alpha 6/alpha 3 beta 2 nAChRs
      with a 40,000-fold lower IC(50) than alpha 4 beta 2 nAChRs. The kinetics of toxin
      unblock are dependent on the beta subunit. nAChRs with a beta 4 subunit have very
      slow off-times, compared with the corresponding beta 2 subunit-containing nAChR.
      In each instance, rat alpha x beta 4 may be distinguished from rat alpha x beta 2
      by the large difference in time to recover from toxin block. Similar results are
      obtained when comparing mouse alpha 3 beta 2 to mouse alpha 3 beta 4, and human
      alpha 3 beta2 to human alpha 3 beta 4, indicating that the beta subunit
      dependence extends across species. Thus, alpha-conotoxin BuIA also represents a
      novel probe for distinguishing between beta 2- and beta 4-containing nAChRs.

PMID- 15520010
TI  - Insulin-induced beta-arrestin1 Ser-412 phosphorylation is a mechanism for
      desensitization of ERK activation by Galphai-coupled receptors.
AB  - Beta-arrestin1 is an adapter/scaffold for many G protein-coupled receptors during
      mitogen-activated protein kinase signaling. Phosphorylation of beta-arrestin1 at
      position Ser-412 is a regulator of beta-arrestin1 function, and in the present
      study, we showed that insulin led to a time- and dose-dependent increase in beta
      arrestin1 Ser-412 phosphorylation, which blocked isoproterenol- and
      lysophosphatidic acid-induced Ser-412 dephosphorylation and impaired ERK
      signaling by these G protein-coupled receptor ligands. Insulin treatment also led
      to accumulation of Ser-412-phosphorylated beta-arrestin1 at the insulin-like
      growth factor 1 receptor and prevented insulin-like growth factor 1/Src
      association. Insulin-induced Ser-412 phosphorylation was partially dependent on
      ERK as treatment with the MEK inhibitor PD98059 inhibited the insulin effect (62%
      reduction, p = 0.03). Inhibition of phosphatidylinositol 3-kinase by wortmannin
      did not have a significant effect (9% reduction, p = 0.41). We also found that
      the protein phosphatase 2A (PP2A) was in a molecular complex with beta-arrestin1
      and that the PP2A inhibitor okadaic acid increased Ser-412 phosphorylation.
      Concomitant addition of insulin and okadaic acid did not produce an additive
      effect on Ser-412 phosphorylation, suggesting a common mechanism. Small t antigen
      specifically inhibited PP2A, and in HIRcB cells expressing small t antigen, beta
      arrestin1 Ser-412 phosphorylation was increased, and insulin had no further
      effect. Insulin treatment caused increased beta-arrestin1 Ser-412
      phosphorylation, which blocked mitogen-activated protein kinase signaling and
      internalization by beta-arrestin1-dependent receptors with no effect on beta
      adrenergic receptor Gs-mediated cAMP production. These findings provide a new
      mechanism for insulin-induced desensitization of ERK activation by Galphai
      coupled receptors.

PMID- 15520011
TI  - alpha2-Macroglobulin-proteinase complexes protect Streptococcus pyogenes from
      killing by the antimicrobial peptide LL-37.
AB  - The significant human bacterial pathogen Streptococcus pyogenes expresses GRAB, a
      surface protein that binds alpha(2)-macroglobulin (alpha(2)M), a major proteinase
      inhibitor of human plasma. alpha(2)M inhibits proteolysis by trapping the
      proteinase, which, however, still remains proteolytically active against smaller
      peptides that can penetrate the alpha(2)M-proteinase complex. Here we report that
      SpeB, a cysteine proteinase secreted by S. pyogenes, is trapped by alpha(2)M
      bound to protein GRAB. As a consequence, SpeB is retained at the bacterial
      surface and protects S. pyogenes against killing by the antibacterial peptide LL
      37.

PMID- 15520012
TI  - Production of the neuromodulator H2S by cystathionine beta-synthase via the
      condensation of cysteine and homocysteine.
AB  - Hydrogen sulfide (H2S) has been observed in relatively high concentrations in the
      mammalian brain and has been shown to act as a neuromodulator. However, there is
      confusion in the literature regarding the actual source of H2S production.
      Reactions catalyzed by the cystathionine beta-synthase enzyme (CBS) are one
      possible source for the production of H2S. Here we show that the CBS enzyme can
      efficiently produce H2S via a beta-replacement reaction in which cysteine is
      condensed with homocysteine to form cystathionine and H2S. The production of H2S
      by this reaction is at least 50 times more efficient than that produced by
      hydrolysis of cysteine alone via beta-elimination. Kinetic studies demonstrate
      that the Km and Kcat for cysteine is 3-fold higher and 2-fold lower,
      respectively, than that for serine. Consistent with these data, in vitro
      reconstitution studies show that at physiologically relevant concentrations of
      serine, homocysteine, and cysteine, about 5% of the cystathionine formed is from
      cysteine. We also show that AdoMet stimulates this H2S producing reaction but
      that there is no evidence for stimulation by calcium and calmodulin as reported
      previously. In summary, these results confirm the ability of CBS to produce H2S,
      but show in contrast to prior reports that the major mechanism is via beta
      replacement and not cysteine hydrolysis. In addition, these studies provide a
      biochemical explanation for the previously inexplicable homocysteine-lowering
      effects of N-acetylcysteine treatments in humans.

PMID- 15520013
TI  - DNA-dependent protein kinase and XRCC4-DNA ligase IV mobilization in the cell in
      response to DNA double strand breaks.
AB  - Repair of DNA double strand breaks (DSBs) by the non-homologous end joining
      (NHEJ) pathway in mammals requires at least the DNA-dependent protein kinase (DNA
      PK) and the DNA ligase IV-XRCC4 protein complexes. DNA-PK comprises the Ku70/Ku80
      heterodimer and the catalytic subunit DNA-PKcs. Here we report the first
      description of the nuclear mobilization of endogenous NHEJ proteins after
      exposure of human cells to double strand-breaking agents. DSB infliction
      specifically induced a dose- and time-dependent mobilization of Ku70/80, DNA
      PKcs, XRCC4, and DNA ligase IV proteins from a soluble nucleoplasmic compartment
      to a less extractable nuclear fraction. XRCC4 recruitment was accompanied by its
      DNA-PK-dependent phosphorylation. The recruited proteins co-immunoprecipitated,
      indicating that they had assembled into complexes. However, DNA-PK was attached
      to chromatin, whereas XRCC4-ligase IV resisted solubilization by DNase I. The
      rates of appearance and dissolution of NHEJ proteins paralleled that of histone
      variant H2AX phosphorylation and dephosphorylation. We established that under
      conditions of genomic DSB infliction 1) Ku recruitment was not dependent on the
      co-recruitment of the other NHEJ proteins, 2) DNA-PKcs was physically required
      for the mobilization of the XRCC4-ligase IV complex, 3) DNA ligase IV was
      physically necessary for stable recruitment of XRCC4, and 4) phosphorylation of
      either H2AX or XRCC4 was unnecessary for DNA-PK or XRCC4-ligase IV recruitment.
      Altogether these results offer insights into the interplay between key NHEJ
      proteins during this repair process in the cell.

PMID- 15520014
TI  - A primer-dependent polymerase function of pseudomonas aeruginosa ATP-dependent
      DNA ligase (LigD).
AB  - Pseudomonas aeruginosa encodes two putative DNA ligases: a classical NAD(+)
      dependent DNA ligase (LigA) plus an ATP-dependent DNA ligase (LigD). LigD
      exemplifies a family of bacterial proteins that consist of a ligase domain fused
      to flanking domains that resemble nucleases and/or polymerases. Here we purify
      LigD and show that it possesses an intrinsic polymerase function resident within
      an autonomous C-terminal polymerase domain, LigD-(533-840), that flanks an
      autonomous DNA ligase domain, LigD-(188-527). Native LigD and the polymerase
      domain are both monomeric proteins. The polymerase activity is manifest in three
      ways: (i) non-templated nucleotide addition to a blunt-ended duplex DNA primer;
      (ii) non-templated addition to a single-stranded DNA primer; and (iii) templated
      extension of a 5'-tailed duplex DNA primer-template. The divalent cation cofactor
      requirement for non-templated and templated polymerase activity is satisfied by
      manganese or cobalt. rNTPs are preferred over dNTPs as substrates for non
      templated blunt-end addition, which typically entails the incorporation of only 1
      or 2 nucleotides at the primer terminus. Templated dNMP addition to a 5'-tailed
      substrate is efficient with respect to dNTP utilization; the primer is elongated
      to the end of the template strand and is then further extended with a non
      templated nucleotide. The polymerase activity is abolished by alanine
      substitution for two aspartates (Asp-669 and Asp-671) within the putative metal
      binding site. We speculate that polymerase activity is relevant to LigD function
      in nonhomologous end-joining.

PMID- 15520015
TI  - Staphylococcus aureus IsdG and IsdI, heme-degrading enzymes with structural
      similarity to monooxygenases.
AB  - Heme-degrading enzymes are involved in human diseases ranging from stroke,
      cancer, and multiple sclerosis to infectious diseases such as malaria,
      diphtheria, and meningitis. All mammalian and microbial enzymes identified to
      date are members of the heme oxygenase superfamily and assume similar monomeric
      structures with an all alpha-helical fold. Here we describe the crystal
      structures of IsdG and IsdI, two heme-degrading enzymes from Staphylococcus
      aureus. The structures of both enzymes resemble the ferredoxin-like fold and form
      a beta-barrel at the dimer interface. Two large pockets found on the outside of
      the barrel contain the putative active sites. Sequence homologs of IsdG and IsdI
      were identified in multiple Gram-positive pathogens. Substitution of conserved
      IsdG amino acid residues either reduced or abolished heme degradation, suggesting
      a common catalytic mechanism. This mechanism of IsdG-mediated heme degradation
      may be similar to that of the structurally related monooxygenases, enzymes
      involved in the synthesis of antibiotics in Streptomyces. Our results imply the
      evolutionary adaptation of microbial enzymes to unique environments.

PMID- 15520016
TI  - Receptor-selective mutants of apoptosis-inducing ligand 2/tumor necrosis factor
      related apoptosis-inducing ligand reveal a greater contribution of death receptor
      (DR) 5 than DR4 to apoptosis signaling.
AB  - Apoptosis-inducing ligand 2 (Apo2L), also called tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL), triggers programmed cell death in various
      types of cancer cells but not in most normal cells. Apo2L/TRAIL is a homotrimeric
      protein that interacts with five receptors: death receptor 4 (DR4) and DR5
      mediate apoptosis activation, whereas decoy receptor 1 (DcR1), DcR2, and
      osteoprotegerin counteract this function. Many cancer cell lines express both DR4
      and DR5, and each of these receptors can initiate apoptosis independently of the
      other. However, the relative contribution of DR4 and DR5 to ligand-induced
      apoptosis is unknown. To investigate this question, we generated death receptor
      selective Apo2L/TRAIL variants using a novel approach that enables phage display
      of mutated trimeric proteins. Selective binding to DR4 or DR5 was achieved with
      three to six-ligand amino acid substitutions. The DR4-selective Apo2L/TRAIL
      variants examined in this study showed a markedly reduced ability to trigger
      apoptosis, whereas the DR5-selective variants had minimally decreased or slightly
      increased apoptosis-inducing activity. These results suggest that DR5 may
      contribute more than DR4 to Apo2L/TRAIL-induced apoptosis in cancer cells that
      express both death receptors.

PMID- 15520017
TI  - Lysosomal acid alpha-glucosidase consists of four different peptides processed
      from a single chain precursor.
AB  - Pompe's disease is caused by a deficiency of the lysosomal enzyme acid alpha
      glucosidase (GAA). GAA is synthesized as a 110-kDa precursor containing N-linked
      carbohydrates modified with mannose 6-phosphate groups. Following trafficking to
      the lysosome, presumably via the mannose 6-phosphate receptor, the 110-kDa
      precursor undergoes a series of complex proteolytic and N-glycan processing
      events, yielding major species of 76 and 70 kDa. During a detailed
      characterization of human placental and recombinant human GAA, we found that the
      peptides released during proteolytic processing remained tightly associated with
      the major species. The 76-kDa form (amino acids (aa) 122-782) of GAA is
      associated with peptides of 3.9 kDa (aa 78-113) and 19.4 kDa (aa 792-952). The 70
      kDa form (aa 204-782) contains the 3.9- and 19.4-kDa peptide species as well as a
      10.3-kDa species (aa 122-199). A similar set of proteolytic fragments has been
      identified in hamster GAA, suggesting that the multicomponent character is a
      general phenomenon. Rabbit anti-peptide antibodies have been generated against
      sequences in the proteolytic fragments and used to demonstrate the time course of
      uptake and processing of the recombinant GAA precursor in Pompe's disease
      fibroblasts. The results indicate that the observed fragments are produced
      intracellularly in the lysosome and not as a result of nonspecific proteolysis
      during purification. These data demonstrate that the mature forms of GAA
      characterized by polypeptides of 76 or 70 kDa are in fact larger molecular mass
      multicomponent enzyme complexes.

PMID- 15520018
TI  - Role of Rho/ROCK and p38 MAP kinase pathways in transforming growth factor-beta
      mediated Smad-dependent growth inhibition of human breast carcinoma cells in
      vivo.
AB  - TGF-beta is a multifunctional cytokine known to exert its biological effects
      through a variety of signaling pathways of which Smad signaling is considered to
      be the main mediator. At present, the Smad-independent pathways, their
      interactions with each other, and their roles in TGF-beta-mediated growth
      inhibitory effects are not well understood. To address these questions, we have
      utilized a human breast cancer cell line MCF10CA1h and demonstrate that p38 MAP
      kinase and Rho/ROCK pathways together with Smad2 and Smad3 are necessary for TGF
      beta-mediated growth inhibition of this cell line. We show that Smad2/3 are
      indispensable for TGF-beta-mediated growth inhibition, and that both p38 and
      Rho/ROCK pathways affect the linker region phosphorylation of Smad2/3. Further,
      by using Smad3 mutated at the putative phosphorylation sites in the linker
      region, we demonstrate that phosphorylation at Ser203 and Ser207 residues is
      required for the full transactivation potential of Smad3, and that these residues
      are targets of the p38 and Rho/ROCK pathways. We demonstrate that activation of
      the p38 MAP kinase pathway is necessary for the full transcriptional activation
      potential of Smad2/Smad3 by TGF-beta, whereas activity of Rho/ROCK is necessary
      for both down-regulation of c-Myc protein and up-regulation of p21waf1 protein,
      directly interfering with p21waf1 transcription. Our results not only implicate
      Rho/ROCK and p38 MAPK pathways as necessary for TGF-beta-mediated growth
      inhibition, but also demonstrate their individual contributions and the basis for
      their cooperation with each other.

PMID- 15520019
TI  - Biomonitoring of titanium, mercury, platinum, rhodium and palladium in dental
      health care workers.
AB  - BACKGROUND: In dentistry, titanium, mercury, platinum, rhodium and palladium are
      used to produce dental fillings. Therefore, dental workers who apply such
      materials may be exposed to these metals. METHODS: The study concerned 40 healthy
      subjects-20 controls and 20 dental health care workers-to determine serum and
      urinary levels of the aforementioned metals by inductively coupled plasma mass
      spectrometry. RESULTS: Mean urinary and serum titanium did not reveal
      statistically significant differences in the two groups. The very low urinary and
      serum levels of mercury, platinum, rhodium and palladium prevented us from making
      a statistical evaluation between the two groups. CONCLUSIONS: We did not find a
      significant increase in serum and urinary titanium levels in dental health care
      workers. Measurement of mercury, platinum, rhodium and palladium in urine and
      serum was not useful in determining occupational exposure.

PMID- 15520020
TI  - The diagnostic value of finger systolic blood pressure and cold-provocation
      testing for the vascular component of hand-arm vibration syndrome in health
      surveillance.
AB  - BACKGROUND: Hand-arm vibration syndrome (HAVS) is a complex condition with
      vascular, sensorineural and musculoskeletal components. A number of quantitative
      tests have been used for assisting in the diagnosis of HAVS and grading disease
      severity. AIMS: To investigate and compare the diagnostic value of finger
      systolic blood pressure (FSBP) and rewarming of finger skin temperature (FST)
      following cold-provocation testing, in the assessment of vascular HAVS. METHODS:
      Twenty-four individuals with vascular HAVS (Stockholm Workshop stage 2 or 3V) and
      22 control subjects underwent FSBP measurements at 30, 15 and 10 degrees C and
      monitoring of FST following immersion of the hands in water at 15 degrees C for 5
      min. RESULTS: There was a significant reduction in median FSBP% in the vascular
      HAVS group in the change in FSBP from 30 to 15 degrees C adjusted for brachial
      blood pressure (FSBPC%). There was no difference in the median time for FST to
      rewarm by 4 degrees C between HAVS cases and controls. The sensitivity and
      specificity of FSBP to discriminate between the groups varied between 44 and 61%
      and 91 and 95%, respectively. The sensitivity and specificity for the time for
      FST to rewarm by 4 degrees C were 71 and 77%. CONCLUSIONS: There is little
      evidence that the described form of finger rewarming after cold-provocation
      testing is a useful diagnostic test for vascular HAVS, although it may have some
      moderate influence in ruling out vascular problems. Based on our data, the FSBP
      may also have limited use in confirming a positive diagnosis of vibration-induced
      vascular problems. The higher specificity of the FSBP test suggests it may have
      some value in ruling out the vascular component of HAVS. The data from this study
      do not confirm the diagnostic power of FSBP for the vascular component of HAVS
      reported by a few other investigators.

PMID- 15520021
TI  - Safe inoculation of blood and bone marrow for liquid culture detection of
      mycobacteria.
AB  - BACKGROUND: Needlestick injuries confer an unnecessary risk of occupational
      bloodborne infections such as human immunodeficiency virus (HIV), hepatitis B
      virus (HBV) and hepatitis C virus (HCV) infections. After an accidental
      needlestick injury, procedures for inoculation of liquid culture media for rapid
      detection of Mycobacterium tuberculosis complex and other mycobacteria from blood
      and bone marrow specimens were reviewed. AIM: To identify a safer transfer
      device, which could replace the ordinary syringe in inoculation of liquid culture
      vials. METHODS: We identified a transfer device to transfer blood or bone marrow
      specimens from bedside tubes into liquid culture vials. CONCLUSION: The changed
      procedure will reduce the risk of needlestick accidents and be of benefit to
      other microbiological laboratories using the same or similar inoculation
      techniques.

PMID- 15520022
TI  - Genome size variation and evolution in Veronica.
AB  - BACKGROUND AND AIMS: The amount of DNA per chromosome set is known to be a fairly
      constant characteristic of a species. Its interspecific variation is enormous,
      but the biological significance of this variation is little understood. Some of
      the characters believed to be correlated with DNA amount are alpine habitat, life
      history and breeding system. In the present study, the aim is to distinguish
      between direct causal connections and chance correlation of the amount of DNA in
      the genus Veronica. METHODS: Estimates of DNA amount were analysed for 42 members
      of Veroniceae in connection with results from a phylogenetic analysis of plastid
      trnL-F DNA sequences and tested correlations using standard statistical tests,
      phylogenetically independent contrasts and a model-based generalized least
      squares method to distinguish the phylogenetic effect on the results. KEY
      RESULTS: There appears to be a lower upper limit for DNA amount in annuals than
      in perennials. Most DNAC-values in Veroniceae are below the mean DNA C-value for
      annuals in angiosperms as a whole. However, the long-debated correlation of low
      genome size with annual life history is not significant (P = 0.12) using either
      standard statistical tests or independent contrasts, but it is significant with
      the generalized least squares method (P < 0.01). CONCLUSIONS: The correlation of
      annual life history and low genome size found in earlier studies could be due to
      the association of annual life history and selfing, which is significantly
      correlated with low genome size using any of the three tests applied. This
      correlation can be explained by models showing a reduction in transposable
      elements in selfers. A significant correlation of higher genome sizes with alpine
      habitats was also detected.

PMID- 15520023
TI  - Aneuploidy study of human oocytes first polar body comparative genomic
      hybridization and metaphase II fluorescence in situ hybridization analysis.
AB  - BACKGROUND: The object of this study was to determine the mechanisms that produce
      aneuploidy in oocytes and establish which chromosomes are more prone to
      aneuploidy. METHODS: A total of 54 oocytes from 36 women were analysed. The whole
      chromosome complement of the first polar body (1PB) was analysed by comparative
      genomic hybridization (CGH), while the corresponding metaphase II (MII) oocyte
      was analysed by fluorescence in situ hybridization (FISH) to confirm the results.
      RESULTS: Matched CGH-FISH results were obtained in 42 1PB-MII doublets, of which
      37 (88.1%) showed reciprocal results. The aneuploidy rate was 57.1%. Two-thirds
      of the aneuploidy events were chromatid abnormalities. Interestingly, the
      chromosomes more frequently involved in aneuploidy were chromosomes 1, 4 and 22
      followed by chromosome 16. In general, small chromosomes (those equal to or
      smaller in size than chromosome 13) were more prone to aneuploidy (chi2-test,
      P=0.07); 25% of the aneuploid doublets would have been misdiagnosed as normal
      using FISH with probes for nine-chromosomes. CONCLUSIONS: The combination of two
      different techniques, CGH and FISH, for the study of 1PB and MII allowed the
      identification and confirmation of any numerical chromosome abnormality, as well
      as helping to determine the mechanisms involved in the genesis of maternal
      aneuploidy.

PMID- 15520024
TI  - No association of the A260G and A386G DAZL single nucleotide polymorphisms with
      male infertility in a Caucasian population.
AB  - BACKGROUND: The human DAZ gene family includes two autosomal genes, BOULE and
      DAZL, and a Y-chromosomal DAZ gene cluster. All are RNA-binding proteins and
      assumed to be master regulators of germline gene expression. We have investigated
      the impact of two DAZL polymorphisms, located at nucleotide positions 260 (SNP
      260) and 386 (SNP 386), on the fertility of Caucasian men. These single
      nucleotide polymorphisms (SNPs) have been described previously to be associated
      with spermatogenic failure. METHODS: Blood samples were collected and genomic DNA
      was extracted from 165 normozoospermic men and 202 oligo- or azoospermic
      patients, of whom 28 displayed an AZFc deletion. The frequencies of A or G
      allelic variants in SNP 260 and 386 were analysed via TaqMan allelic
      discrimination assays. In both cases, the A to G transition leads to a threonine
      to alanine change. RESULTS: A total of 24.2% of the controls showed a
      heterozygous nucleotide variant (AG) for the SNP 260 and the remaining 75.8% were
      homozygous for A. In the AZFc-deleted group, this distribution was significantly
      different, with 39.3% for AG, 57.1% for AA and 3.6% for GG. However, the
      increased heterozygosity was not correlated with sperm counts and morphology. The
      patients without deletions displayed a similar allelic pattern to the controls
      (24.1% AG/75.9% AA). For SNP 386, only the AA nucleotide variant was found in all
      subjects studied and in no case was the previously described heterozygous AG
      variant found. CONCLUSION: In a selected Caucasian population, the DAZL SNP 386
      is completely absent and SNP 260 is not associated with spermatogenic failure and
      therefore does not represent a molecular marker for genetic diagnosis of male
      infertility.

PMID- 15520025
TI  - Developing pineapple fruit has a small transcriptome dominated by
      metallothionein.
AB  - In a first step toward understanding the molecular basis of pineapple fruit
      development, a sequencing project was initiated to survey a range of expressed
      sequences from green unripe and yellow ripe fruit tissue. A highly abundant
      metallothionein transcript was identified during library construction, and was
      estimated to account for up to 50% of all EST library clones. Library clones with
      metallothionein subtracted were sequenced, and 408 unripe green and 1140 ripe
      yellow edited EST clone sequences were retrieved. Clone redundancy was high, with
      the combined 1548 clone sequences clustering into just 634 contigs comprising 191
      consensus sequences and 443 singletons. Half of the EST clone sequences clustered
      within 13.5% and 9.3% of contigs from green unripe and yellow ripe libraries,
      respectively, indicating that a small subset of genes dominate the majority of
      the transcriptome. Furthermore, sequence cluster analysis, northern analysis, and
      functional classification revealed major differences between genes expressed in
      the unripe green and ripe yellow fruit tissues. Abundant genes identified from
      the green fruit include a fruit bromelain and a bromelain inhibitor. Abundant
      genes identified in the yellow fruit library include a MADS box gene, and several
      genes normally associated with protein synthesis, including homologues of
      ribosomal L10 and the translation factors SUI1 and eIF5A. Both the green unripe
      and yellow ripe libraries contained high proportions of clones associated with
      oxidative stress responses and the detoxification of free radicals.

PMID- 15520026
TI  - Metabolite fingerprinting and profiling in plants using NMR.
AB  - Although less sensitive than mass spectrometry (MS), nuclear magnetic resonance
      (NMR) spectroscopy provides a powerful complementary technique for the
      identification and quantitative analysis of plant metabolites either in vivo or
      in tissue extracts. In one approach, metabolite fingerprinting, multivariate
      analysis of unassigned 1H NMR spectra is used to compare the overall metabolic
      composition of wild-type, mutant, and transgenic plant material, and to assess
      the impact of stress conditions on the plant metabolome. Metabolite
      fingerprinting by NMR is a fast, convenient, and effective tool for
      discriminating between groups of related samples and it identifies the most
      important regions of the spectrum for further analysis. In a second approach,
      metabolite profiling, the 1H NMR spectra of tissue extracts are assigned, a
      process that typically identifies 20-40 metabolites in an unfractionated extract.
      These profiles may also be used to compare groups of samples, and significant
      differences in metabolite concentrations provide the basis for hypotheses on the
      underlying causes for the observed segregation of the groups. Both approaches
      generate a metabolic phenotype for a plant, based on a system-wide but incomplete
      analysis of the plant metabolome. However, a review of the literature suggests
      that the emphasis so far has been on the accumulation of analytical data and
      sample classification, and that the potential of 1H NMR spectroscopy as a tool
      for probing the operation of metabolic networks, or as a functional genomics tool
      for identifying gene function, is largely untapped.

PMID- 15520027
TI  - PIP1 and PIP2 aquaporins are differentially expressed during tobacco anther and
      stigma development.
AB  - Several processes during sexual reproduction in higher plants involve the
      movement of water between cells or tissues, such as occurs during dehiscence of
      the anther and hydration of the pollen grain after it is deposited on a stigma.
      To get more insight in these processes, a set of putative aquaporins was cloned
      and it was found that at least 15 are expressed in reproductive organs, which
      indicates that the control of water flow is important for reproduction.
      Functional studies in Xenopus laevis oocytes using two of the cDNAs showed that
      NtPIP2;1 is an efficient aquaporin, whereas NtPIP1;1 is not. Expression studies
      on RNA and protein levels showed that PIP1 and PIP2 genes are differently
      expressed in reproductive organs: PIP1 RNA accumulates in the stigma, and PIP1
      and PIP2 RNA can be detected in most tissues of the anther.

PMID- 15520028
TI  - Effect of sucrose on ascorbate level and expression of genes involved in the
      ascorbate biosynthesis and recycling pathway in harvested broccoli florets.
AB  - The relationship between sucrose (Suc) and ascorbate (AA) metabolism was
      investigated in harvested broccoli (Brassica oleracea L. var. italica) florets.
      Decreases in both Suc and AA content were observed in broccoli florets 48 h after
      all the leaves were excised, but none were observed when the plants were kept
      intact or with leaves attached in a room at 20 degrees C. In harvested broccoli
      plants without leaves and roots, continuous absorption of a 10% (w/v) Suc
      solution from the cut surface of the stem suppressed the degreening of sepals and
      the loss of AA content in florets. The expression of the genes related to AA
      metabolism in chloroplasts and its biosynthesis were up-regulated by Suc feeding
      in broccoli florets. These data suggest that a decline in Suc leads to
      considerable damage not only to AA biosynthesis but also to the hydrogen peroxide
      scavenging system in chloroplasts. In addition, the cessation of the Suc supply
      from leaves can be the main factor of AA degradation in harvested broccoli
      florets.

PMID- 15520029
TI  - Localization of ascorbic acid, ascorbic acid oxidase, and glutathione in roots of
      Cucurbita maxima L.
AB  - To understand the function of ascorbic acid (ASC) in root development, the
      distribution of ASC, ASC oxidase, and glutathione (GSH) were investigated in
      cells and tissues of the root apex of Cucubita maxima. ASC was regularly
      distributed in the cytosol of almost all root cells, with the exception of
      quiescent centre (QC) cells. ASC also occurred at the surface of the nuclear
      membrane and correspondingly in the nucleoli. No ASC could be observed in
      vacuoles. ASC oxidase was detected by immunolocalization mainly in cell walls and
      vacuoles. This enzyme was particularly abundant in the QC and in differentiating
      vascular tissues and was absent in lateral root primordia. Administration of the
      ASC precursor L-galactono-gamma-lactone markedly increased ASC content in all
      root cells, including the QC. Root treatment with the ASC oxidized product,
      dehydroascorbic acid (DHA), also increased ASC content, but caused ASC
      accumulation only in peripheral tissues, where DHA was apparently reduced at the
      expense of GSH. The different pattern of distribution of ASC in different tissues
      and cell compartments reflects its possible role in cell metabolism and root
      morphogenesis.

PMID- 15520030
TI  - The narrative approach as an effective single intervention in functional somatic
      symptoms in a multi-disciplinary referral clinic for primary care frequent
      attenders.
AB  - Mental health problems are underdiagnosed in general practice, primarily because
      they are often somatized and the patient reports only physical symptoms. These
      somatized symptoms are responsible for a large percentage of the frequent
      attenders in general practice. Palpitations are among those somatized symptoms.
      Here we present the theoretical background and the process of assessment and
      treatment of patients referred to a special counselling clinic for frequent
      attenders, through the report of a patient with palpitations. It illustrates the
      use of the narrative approach and the possible mode of action of this specific
      intervention.

PMID- 15520031
TI  - Applying the theory of planned behaviour to pharmacists' beliefs and intentions
      about the treatment of vaginal candidiasis with non-prescription medicines.
AB  - BACKGROUND: It is important to understand health professionals' attitudes and
      beliefs about practice and the barriers to achieving best practice. The theory of
      planned behaviour (TPB) has been widely used to understand behaviour. In this
      study, TPB was used to explore the psychological variables that influence
      community pharmacists and the supply of non-prescription medicines. OBJECTIVES:
      The objectives of the study were to: (i) apply the TPB to community pharmacy
      behaviour; (ii) identify barriers to/facilitators of evidence-based practice;
      (iii) describe psychological variables and responses to written scenarios of
      patients presenting in community pharmacies for non-prescription antifungals for
      the treatment of vulvovaginal candidiasis; and (iv) to examine the relationships
      between beliefs and behavioural intention. METHODS: A questionnaire survey was
      constructed using the TPB and disseminated to pharmacies in Grampian, Scotland.
      The purpose of the study was to explore community pharmacists' attitudes, beliefs
      and intentions about the supply of non-prescription antifungals for the treatment
      of vulvovaginal candidiasis. RESULTS: Of the 121 questionnaires disseminated, 76
      (63%) were returned. Behavioural intention to sell antifungals to women with
      vulvovaginal candidiasis symptoms was strong. Attitude towards recommending these
      medicines was positive. However, only half of the sample responded appropriately
      to all four patient scenarios (n=42, 54%). Most pharmacists felt that they were
      able to recommend antifungals if they wished, but did not feel under social
      pressure to recommend them. Local doctors did not appear to be influential with
      respect to selling antifungals. If a customer was elderly, pregnant or if the
      pharmacist was uncertain of the diagnosis of candidiasis, an antifungal was less
      likely to be recommended. CONCLUSION: TPB provides a valid and useful summary of
      the key psychological variables influencing practice. There is more to pharmacy
      practice than the knowledge and attitudes of the pharmacist.

PMID- 15520032
TI  - The impact of matching the patient's vocabulary: a randomized control trial.
AB  - BACKGROUND: Research in general practice emphasizes the importance of matched
      models, beliefs and vocabulary in the consultation. OBJECTIVE: The present study
      aimed to explore the impact of matched and unmatched vocabulary on patient
      satisfaction with consultations. METHODS: The study took place in one inner city
      general practice. Patients (n=62) were randomized to either matched or unmatched
      vocabulary consultations when consulting for problems relating to sexual or
      bodily function or anatomy. Matched consultations required the doctor to use the
      same vocabulary as the patient. Unmatched consultations required the doctor to
      use medical vocabulary. Completed questionnaires were received from 60 patients.
      The main outcome measure was patient satisfaction (using the Medical Interview
      Satisfaction Scale). This assesses total satisfaction and has four subscales:
      distress relief; communication comfort; rapport; and compliance intent. Doctor
      satisfaction with the consultation was also assessed. RESULTS: The results showed
      that the two groups were comparable for demographic variables and doctor
      satisfaction. However, patients in the matched consultation group had
      significantly higher total satisfaction scores and higher ratings of rapport,
      communication comfort, distress relief and compliance intent than those in the
      unmatched group. CONCLUSION: The results indicate that a doctor's choice of
      vocabulary affects patient satisfaction immediately after a general practice
      consultation and that using the same vocabulary as the patient can improve
      patient outcomes.

PMID- 15520033
TI  - Prospective study of elderly people comparing treatments following first primary
      care consultation for a symptomatic hip or knee.
AB  - BACKGROUND: Symptomatic knee problems in elderly people are considerably more
      common than hip problems, yet far more hips are replaced. OBJECTIVE: The purpose
      of this study was to investigate whether systematic differences occur in early
      primary care management of elderly patients who first consult with hip versus
      knee symptoms. METHODS: A prospective analysis was carried out of anonymized
      records in the MediPlus general practice database. This was a 3 year (1996-1998)
      prospective study of 310,843 patients aged 65+ regarding consultations about a
      new hip or knee problem. Survival analysis techniques were used to analyse time
      to and frequency of various interventions. RESULTS: A total of 1410 new hip and
      3152 new knee consulters were identified. Baseline characteristics of the two
      groups were very similar. By 3 years following the first consultation, more of
      the hip cases had referral to a specialist (38.2% hips versus 31.5% knees, P
      <0.001) and joint replacement (9.6% hips versus 1.8% knees, P <0.001) recorded.
      Non-steroidal anti-inflammatory drug (NSAID) prescribing was high for both
      groups, with approximately 51% prescribed one of the safer forms and
      approximately 15% prescribed one with a lower safety record within 3 years.
      CONCLUSION: Rates of specialist referral and joint replacement in older people
      are much lower, or slower, for those with symptomatic knees relative to hips. In
      the absence of surgery, prescriptions for pain killers are similar for both
      groups. Elderly people with symptomatic knees are therefore at increased risk of
      drug side effects relative to those with symptomatic hips. This may represent
      another facet of unmet need for surgery in people with knee disease.

PMID- 15520034
TI  - Early discontinuation of antidepressants in general practice: association with
      patient and prescriber characteristics.
AB  - BACKGROUND: Most antidepressant treatment is initiated and continued in general
      practice but, despite current guidelines, treatment duration is often short among
      patients with depression. Discontinuation may, however, be caused by a complexity
      of factors, but so far research has focused on drug effects, adverse effects and
      drug regimens. OBJECTIVE: Our aim was to analyse whether early discontinuation of
      first-time antidepressant treatment in general practice may be predicted by (i)
      social position and psychiatric history of the patient; and (ii) demography,
      practice activity and the general prescribing behaviour of the GP. METHODS: Early
      discontinuation, i.e. that patients do not purchase antidepressants in the 6
      months following first prescription, was analysed using established databases.
      Among patients presenting in 174 general practices in Funen County, Denmark, 4860
      adult first-time users of antidepressants were identified (regardless of
      diagnosis). The inclusion period was January 1998-June 1999. RESULTS: One in
      three patients did not purchase antidepressants in the 6 months following first
      prescription, but rates were higher among those prescribed tricyclic compared
      with new generation antidepressants. Patients' age and sex did not have an
      influence, but early discontinuation was more frequent among patients of low
      socio-economic status and patients prescribed in practices characterized by high
      prescribing rates. No association with psychiatric history was observed.
      CONCLUSION: Early discontinuation is frequent in general practice, and patients
      of low social status are at greater risk. Adherence-promoting strategies should
      pay attention to the high prescribing doctors. Further studies may answer the
      question of whether the association between doctors' prescribing behaviour and
      early discontinuation is a feature specific to antidepressants or a more general
      phenomenon.

PMID- 15520035
TI  - Diagnosis of lung cancer in primary care: a structured review.
AB  - BACKGROUND: Lung cancer has the highest cancer incidence and mortality in the UK.
      Despite this, an individual GP encounters only one new presentation approximately
      every 8 months, so gains relatively little experience of its diagnosis. This is
      partly addressed by referral guidelines which aim to help GPs in selection of
      patients for chest X-ray or referral for specialist investigation. OBJECTIVE: The
      purpose of this study was to review the primary care presenting features of lung
      cancer, in the light of the UK Referral Guidelines for Suspected Cancer. METHODS:
      A structured literature review was carried out. RESULTS: Little research has been
      undertaken in primary care, and the predictive values for most symptoms are
      unknown. Approximate likelihood ratios could be calculated for six symptoms or
      signs: haemoptysis 13; fatigue 5.7; cough 5.3; finger clubbing 3.9; weight loss
      2.9; and dyspnoea 1.5-5.7, but none of these figures derived from single primary
      care studies. Three recommendations for urgent investigation of possible lung
      cancer in the UK Referral Guidelines are questioned: for unexplained dyspnoea,
      hoarseness or cervical lymphadenopathy. For all these presentations, other
      serious diagnoses are more likely. CONCLUSION: The UK Guidelines for referral of
      suspected lung cancer have a weak evidence base.

PMID- 15520036
TI  - Program sustainability: focus on organizational routines.
AB  - Program sustainability is an ongoing concern for most people in health promotion.
      However, the current notion of sustainability in organizations, namely
      routinization, needs refinement. This article examines organizational routines.
      In so doing, it refines the notion of sustainability and the assessment of
      routines. Drawing on the organizational literature, a routinized program is
      defined by the presence of routinized activities, meaning that these activities
      exhibit four characteristics of organizational routines: memory, adaptation,
      values and rules. To answer the question of how these characteristics are useful,
      we conducted an empirical study of the routinization of the Quebec Heart Health
      Demonstration Project in five community health centers. Our method consisted of a
      multiple-case study. We observed project activities in each center in 2000. The
      data came from documents and interviews with project actors. Our results show
      that, in one of the centers, no resources had been officially committed to
      project activities. Even so, the actors continued some activities on an informal
      basis. In another center, the activities satisfied three of the four routine
      characteristics. In the three others, activities satisfied all of the
      characteristics. These results suggest focusing the study of program
      sustainability on the routinization of activities resulting from it. They
      indicate four distinct degrees of sustainability: (1) the absence of
      sustainability; no program activity is continued; (2) precarious sustainability;
      some residual activities are pursued, at least unofficially; (3) weak
      sustainability; the program produces some official activities that are not
      routinized; and (4) sustainability through routinization; routinized activities
      result from the program.

PMID- 15520037
TI  - Towards the development of scales to measure 'will' to promote heart health
      within health organizations in Canada.
AB  - This paper describes the development and psychometric evaluation of scales
      measuring the dimensions of 'will' (belief, confidence, prior action and desire)
      for heart health promotion specifically and health promotion in general at both
      an individual and organizational level. Content validity was established through
      a series of focus groups and expert opinion assessments, based on a compilation
      of capacity-assessment instruments developed by other provinces involved in the
      Canadian Heart Health Initiative and the literature. Psychometric analyses of
      questionnaire data provided empirical evidence of the construct validity and
      reliability of the 16 individual and 21 organizational level 'will' scales. A
      series of principal component analyses assisted in verifying the
      unidimensionality of the measures and all scales yielded high internal
      consistencies with Cronbach's alpha coefficients ranging between 0.73 and 0.96.
      These measures can be used by both researchers and practitioners for assessing
      the 'will' to promote heart health specifically and health promotion in general.

PMID- 15520038
TI  - The effect of health education interventions on child malaria treatment-seeking
      practices among mothers in rural refugee villages in Belize, Central America.
AB  - This paper reports on a study conducted to examine the effect of health education
      interventions on mothers' treatment-seeking behaviors for their children's
      malaria fevers. The study used a quasi-experimental post-test community-based
      design with an intervention and control group. A post-intervention survey was
      conducted to assess knowledge, attitudes and child fever and malaria treatment
      seeking behaviors and access and exposure to health messages. Survey results
      indicated that some health education interventions, especially interpersonal
      communication, appeared to have a positive impact on fever and malaria beliefs
      and attitudes and on positive treatment-seeking behaviors. While some
      interventions appeared to have a positive impact on fever and malaria beliefs and
      attitudes and on positive treatment-seeking behaviors, limitations in the study
      design made assigning specific effects to the interventions difficult. However,
      health education interventions remain a valuable tool in addressing malaria in
      children.

PMID- 15520040
TI  - Cigarette access and pupil smoking rates: a circular relationship?
AB  - Adolescents obtain cigarettes from both commercial and social sources. While the
      relationship between commercial access and adolescent smoking has been
      researched, no one has considered in detail whether rates of peer smoking affect
      cigarette availability. In two relatively deprived Scottish schools that differed
      in their pupil smoking rates, we assess pupil access to cigarettes. 896 13 and 15
      year olds were surveyed, and 25 single-sex discussion groups held with a sub
      sample of the 13 year olds. Smokers in both schools obtained cigarettes from
      shops, food vans and other pupils. However, pupils in the 'high' smoking school
      perceived greater access to both commercial and social sources, and had access to
      an active 'peer market'. These findings suggest that variations in cigarette
      access may contribute to school differences in pupil smoking rates, and that the
      relationship between access and adolescent smoking is circular, with greater
      availability increasing rates, and higher rates enhancing access.

PMID- 15520039
TI  - Acceptability and feasibility of a community-based screening programme for
      melanoma in Australia.
AB  - The evaluation of a community-based screening programme for melanoma (SkinWatch)
      in 18 regional communities (total adult population >30 years 63 035) in
      Queensland, Australia is described. The aim of the SkinWatch programme was to
      promote whole-body skin screening for melanoma by primary care physicians. The
      programme included community education, education and support for local medical
      practitioners and open-access skin screening clinics. Programme delivery was
      achieved through assistance of local volunteers. All programme activities and
      resources were recorded for process evaluation. A baseline telephone survey (n =
      3110) and a telephone survey four months after programme launch (n = 680)
      assessed community awareness of the SkinWatch programme and, 37 face-to-face
      interviews with community members, doctors and community leaders were conducted
      to assess satisfaction with the programme. A sample of 1043 of 16,383 residents
      who attended the skin screening clinics provided as part of the programme were
      interviewed to assess reasons for attending, and positive and negative aspects of
      SkinWatch programme. Community awareness of the SkinWatch programme increased by
      over 30% (p < 0.001) within four months of the start of the programme. Interview
      participants described the SkinWatch programme as a useful service for the
      communities and 90% stated they would revisit the clinics. A total of 43% of all
      attendees were over 50 years old, and nearly 50% were men. These findings
      demonstrate the acceptability and feasibility of a community-based screening
      programme for melanoma in rural areas. Volunteers were instrumental in increasing
      community ownership of and involvement in the SkinWatch programme.

PMID- 15520041
TI  - How can critical incidents be used to describe health promotion in the Finnish
      European Network of Health Promoting Schools?
AB  - The purpose of this study was to elicit critical incidents that illustrate the
      reality in which health promotion processes take place in the Finnish European
      Network of Health Promoting Schools (ENHPS). In this study, critical incidents
      were used as a data collection method. The data were collected by asking
      representatives (n = 30) of the schools to describe in writing both positive and
      negative critical incidents related to health promotion in their school
      community. Altogether 48 critical incidents were analysed using qualitative
      content analysis. The results show that collaboration in a network of
      participants from inside and outside the school community to plan and implement a
      special school health day was the most commonly described positive critical
      incident. In addition, the organizational culture of the schools seemed to
      improve in a positive way. The reorganization of resources for health promotion
      resulted in positive progress, whereas a lack of resources had a frustrating and
      negative effect. The most commonly described negative critical incident was a
      failure to discourage smoking by pupils.

PMID- 15520042
TI  - Creating health-promoting schools in China with a focus on nutrition.
AB  - This pilot project in Zhejiang Province, China, aimed at improving the nutrition
      and health status of students, school personnel and parents, and developing a
      model project for nutrition interventions for the development of health-promoting
      schools (HPS) in China. Three primary and three secondary schools participated.
      Interventions included establishing school-based working groups, nutrition
      training for school staff, distribution of materials on nutrition, nutrition
      education for students, student competitions, school-wide health promotion
      efforts and outreach to families and communities. Results of a pre- and post
      intervention survey one and a half years apart showed improvements in nutrition
      knowledge, attitudes and behavior among all target groups. Primary school
      students at the pilot schools made the greatest knowledge gains in the areas of
      Chinese dietary guidelines (increased from 49.2 to 78.0%, p < 0.01) and adequate
      dietary principles (increased from 42.9 to 68.0%, p < 0.01). Scores of secondary
      school students who reported liking school lunches rose at pilot schools from
      17.9 to 45.2% (p < 0.01). School staff at control schools who reported taking
      breakfast declined from 81.4 to 66.6% (p < 0.01), while staff who reported taking
      lunch at school increased in pilot schools from 87.5% at baseline to 93.9% (p <
      0.01). The largest increases in nutrition knowledge among all target groups
      occurred among parents and guardians. At the pilot schools parents increased
      their knowledge in the areas of nutritional deficiencies (from 35.0 to 66.2%, p <
      0.01) and nutrient-rich foods (from 38.8 to 66.8%, p < 0.01). Talks with target
      groups confirmed changes in attitudes and behavior, and school visits revealed
      improvements to school facilities and school health services, establishing of
      school policies and a positive school climate. This study suggests that nutrition
      can effectively serve as an entry point to establish HPS in China and that the
      HPS concept is feasible to improve the dietary knowledge, attitudes and behavior
      of students, parents and school personnel.

PMID- 15520043
TI  - The impact of splenectomy on antiviral T cell memory in mice.
AB  - The contribution of the spleen to protective antiviral T cell memory was studied
      using the mouse model of infection with respiratory syncytial virus (RSV). Virus
      specific CD8+ memory T cells were induced by local (intranasal or intracutaneous)
      or systemic (intravenous) immunization using RSV or vaccinia virus-recombinants
      expressing an RSV protein. After all three routes of immunization, the spleen was
      clearly identified as the main anatomic compartment harbouring virus-specific
      memory T cells. Surprisingly, however, splenectomy performed 30 days after
      immunization did not impair the efficacy of the memory T cell response to a
      subsequent RSV challenge infection. Irrespective of the route of priming,
      splenectomy did not influence the number or the functional activity of virus
      specific memory T cells recruited to the lung following RSV challenge. More
      importantly, splenectomy did not impair pulmonary virus control by antiviral
      memory T cells in vivo. These findings were confirmed under experimental
      conditions where no neutralizing antibodies were induced by the priming
      infection. Thus, although most memory CD8+ T cells localize to the spleen after
      viral infections, this important lymphoid organ is dispensable for efficient
      recall responses. These findings have implications for the immunocompetence of
      splenectomized patients.

PMID- 15520044
TI  - Altered splenic B cell subset development in mice lacking phosphoinositide 3
      kinase p85alpha.
AB  - The signaling enzyme phosphoinositide 3-kinase (PI3K) is activated following B
      cell receptor (BCR) engagement and by many other receptors on B lymphocytes. Mice
      lacking p85alpha, the predominant PI3K regulatory isoform, exhibit defects in B
      cell development and activation that are grossly similar to those found in mice
      lacking Bruton's tyrosine kinase (Btk) and other critical signaling molecules.
      However, a detailed analysis of splenic B cell subsets in p85alpha-deficient mice
      has not been reported. Here we show that these mice are deficient in four major B
      cell subsets: transitional-1, transitional-2, follicular and marginal zone. These
      defects are distinct from those observed in Xid mice that express a mutant Btk
      unable to interact with PI3K lipid products. Moreover, mice with both genetic
      lesions exhibit even greater impairment in B cell development. Finally, we show
      that transgenic expression of the anti-apoptotic protein Bcl-2 in p85alpha
      deficient mice restores the transitional B cell subsets but not the marginal zone
      subset, and produces a follicular population with an aberrant phenotype. These
      findings establish a role for PI3K-p85alpha in differentiation of both follicular
      and marginal zone B cells, and suggest that these functions are required not
      solely for the propagation of anti-apoptotic signals.

PMID- 15520045
TI  - Control of Foxp3+ CD25+CD4+ regulatory cell activation and function by dendritic
      cells.
AB  - Naturally occurring CD4+CD25+ regulatory T (TR) cells play crucial roles in
      normal immunohomeostasis. CD4+CD25+ TR cells exhibit a number of interesting in
      vitro properties including a 'default state' of profound anergy refractory to
      conventional T cell stimuli. We investigated the in vitro activation requirements
      of CD4+CD25+ TR cells using bone marrow-derived DC, which as professional antigen
      presenting cells (APC) can support the activation of normal naive T cells.
      Comparison of different APC types revealed that LPS-matured DC were by far the
      most effective at breaking CD4+CD25+ TR cell anergy and triggering proliferation,
      and importantly their IL-2 production. Examination of Foxp3, a key control gene
      for CD4+CD25+ TR cells, showed this to be stably expressed even during active
      proliferation. Although CD4+CD25+ TR cell proliferation was equivalent to that of
      CD25- cells their IL-2 production was considerably less. Use of IL-2-/- mice
      demonstrated that the DC stimulatory ability was not dependent on IL-2
      production; nor did IL-15 appear crucial but was, at least in part, related to
      costimulation. DC also blocked normal CD4+CD25+ TR cell-mediated suppression
      partially via IL-6 secretion. DC therefore possess novel mechanisms to control
      the suppressive ability, expansion and/or differentiation of CD4+CD25+ TR cells
      in vivo.

PMID- 15520048
TI  - Increased fasting plasma ghrelin levels during alcohol abstinence.
AB  - AIMS: Ghrelin is a peptide hormone that antagonizes the action of leptin and is
      thereby thought to regulate feeding behaviour. The actions of ghrelin and leptin
      appear to be mediated by the neuropeptide Y (NPY) and Agouti-related protein
      (AGRP) system. Recent studies have suggested that leptin and NPY play significant
      roles in the pathophysiology of alcoholism. The aim of this study was to
      determine whether ghrelin is associated with the state and duration of abstinence
      in individuals with alcohol dependence. METHODS: Fasting plasma ghrelin levels
      were compared between 47 individuals with chronic alcoholism during a period of
      abstinence and 50 control subjects. RESULTS: Fasting plasma ghrelin levels were
      higher in alcohol abstainers than those in controls. Furthermore, a positive
      correlation was observed between ghrelin levels and the duration of abstinence.
      In addition, daily alcohol intake prior to abstinence was inversely related to
      ghrelin levels. CONCLUSIONS: These findings suggest that ghrelin plays a role in
      the pathogenesis of alcohol dependence, particularly during the abstinence
      period, in individuals with chronic alcoholism.

PMID- 15520046
TI  - Kinin B1 receptors: key G-protein-coupled receptors and their role in
      inflammatory and painful processes.
AB  - Kinins are a family of peptides implicated in several pathophysiological events.
      Most of their effects are likely mediated by the activation of two G-protein
      coupled receptors: B(1) and B(2). Whereas B(2) receptors are constitutive
      entities, B(1) receptors behave as key inducible molecules that may be
      upregulated under some special circumstances. In this context, several recent
      reports have investigated the importance of B(1) receptor activation in certain
      disease models. Furthermore, research on B(1) receptors in the last years has
      been mainly focused in determining the mechanisms and pathways involved in the
      process of induction. This was essentially favoured by the advances obtained in
      molecular biology studies, as well as in the design of selective and stable
      peptide and nonpeptide kinin B(1) receptor antagonists. Likewise, development of
      kinin B(1) receptor knockout mice greatly helped to extend the evidence about the
      relevance of B(1) receptors during pathological states. In the present review, we
      attempted to remark the main advances achieved in the last 5 years about the
      participation of kinin B(1) receptors in painful and inflammatory disorders. We
      have also aimed to point out some groups of chronic diseases, such as diabetes,
      arthritis, cancer or neuropathic pain, in which the strategic development of
      nonpeptidic oral-available and selective B(1) receptor antagonists could have a
      potential relevant therapeutic interest.

PMID- 15520049
TI  - Perspectives, preferences, care practices, and outcomes in late-stage cancer
      patients: connecting the dots.

PMID- 15520047
TI  - Antihyperalgesic effect of pentoxifylline on experimental inflammatory pain.
AB  - The antihyperalgesic effect of pentoxifylline was investigated in three
      experimental pain models. Pentoxifylline (0.5-1.6 mg kg(-1)) given 30 min before
      the stimulus significantly inhibited the writhing response induced by the
      intraperitoneal (i.p.) administration of either acetic acid (-90%) or zymosan (
      83%), but not that of iloprost, in mice, as well as the zymosan-induced articular
      hyperalgesia in the zymosan arthritis in rats (-50%). Pentoxifylline also
      inhibited the mechanical hypernociception in rats induced by the intraplantar
      injection of either carrageenin (-81%), bradykinin (-56%) or tumor necrosis
      factor alpha (TNF-alpha; -46%), but not that induced by interleukin-1beta (IL
      1beta) or prostaglandin E(2) (PGE(2)). Pentoxifylline did not inhibit the
      nociceptive response in the hot plate test in mice. Further, the antinociceptive
      effect of pentoxifylline in the writhing test in mice and the zymosan-induced
      articular hyperalgesia were not reversed by the coadministration of the opioid
      receptor antagonist naloxone. Thus, pentoxifylline antinociceptive effect is
      probably not mediated at a central level. Pentoxifylline significantly reduced
      TNF-alpha (-43%) and IL-1beta (-42%) concentrations in the joint exudates of rats
      stimulated by intra-articular injection of zymosan and the production of both
      cytokines (-66 and -86%, respectively) by mouse peritoneal macrophages stimulated
      in vivo with zymosan as well as the expression of TNF-alpha at the tissue level
      in carrageenin-injected rat paws. In conclusion, the antinociceptive activity of
      pentoxifylline is associated with the inhibition of the release of both TNF-alpha
      and IL-1beta.

PMID- 15520050
TI  - Mandibular osteoradionecrosis.

PMID- 15520051
TI  - Allogeneic peripheral blood versus bone marrow transplantation: children are
      small adults and more.

PMID- 15520052
TI  - Hyperbaric oxygen therapy for radionecrosis of the jaw: a randomized, placebo
      controlled, double-blind trial from the ORN96 study group.
AB  - PURPOSE: To determine the efficacy and safety of hyperbaric oxygen therapy (HBO)
      for overt mandibular osteoradionecrosis. PATIENTS AND METHODS: This prospective,
      multicenter, randomized, double-blind, placebo-controlled trial was conducted at
      12 university hospitals. Ambulatory adults with overt osteoradionecrosis of the
      mandible were assigned to receive 30 HBO exposures preoperatively at 2.4 absolute
      atmosphere for 90 minutes or a placebo, and 10 additional HBO dives
      postoperatively or a placebo. The main outcome measure was 1-year recovery rate
      from osteoradionecrosis. Secondary end points included time to treatment failure,
      time to pain relief, 1-year mortality rate, and treatment safety. RESULTS: At the
      time of the second interim analysis, based on the triangular test, the study was
      stopped for potentially worse outcomes in the HBO arm. A total of 68 patients
      were enrolled and analyzed. At 1 year, six (19%) of 31 patients had recovered in
      the HBO arm and 12 (32%) of 37 in the placebo arm (relative risk = 0.60; 95% CI,
      0.25 to 1.41; P = .23). Time to treatment failure (hazard ratio = 1.33; 95% CI,
      0.68 to 2.60; P = .41) and time to pain relief (hazard ratio = 1.00; 95% CI, 0.52
      to 1.89; P = .99) were similar between the two treatment arms. CONCLUSION:
      Patients with overt mandibular osteoradionecrosis did not benefit from hyperbaric
      oxygenation.

PMID- 15520053
TI  - Recommendations for a global core curriculum in medical oncology.

PMID- 15520054
TI  - Perspectives, preferences, care practices, and outcomes among older and middle
      aged patients with late-stage cancer.
AB  - PURPOSE: To evaluate relationships among physician and cancer patient survival
      estimates, patients' perceived quality of life, care preferences, and outcomes,
      and how they vary across middle-aged and older patient groups. PATIENTS AND
      METHODS: Subjects were from the Study to Understand Prognoses and Preferences for
      Risks of Treatments (SUPPORT) prospective cohort studied in five US teaching
      hospitals (from 1989 to 1994), and included 720 middle-aged (45 to 64 years) and
      696 older (> or = 65 years) patients receiving care for advanced cancer.
      Perspectives were assessed in physician and patient/surrogate interviews; care
      practices and outcomes were determined from hospital records and the National
      Death Index. General linear models were used within age groups to obtain adjusted
      estimates. RESULTS: Although most patients had treatment goals to relieve pain,
      treatment preferences and care practices were linked only in the older group. For
      older patients, preference for life-extending treatment was associated with more
      therapeutic interventions and more documented discussions; cardiopulmonary
      resuscitation (CPR) preference was linked to more therapeutic interventions and
      longer survival. For middle-aged patients, better perceived quality of life was
      associated with preferring CPR. In both groups, patients' higher survival
      estimates were associated with preferences for life-prolonging treatment and CPR;
      physicians' higher survival estimates were associated with patients' preferences
      for CPR, fewer documented treatment limitation discussions about care, and actual
      6-month survival. More discussions were associated with readmissions and earlier
      death. More aggressive care was not related to outcomes. CONCLUSION: Fewer older
      patients preferred CPR or life-prolonging treatments. Although older patients'
      goals for aggressive treatment were related to care, this was not so for middle
      aged patients. Aggressive care was not related to prolonged life in either group.

PMID- 15520055
TI  - Higher mortality after allogeneic peripheral-blood transplantation compared with
      bone marrow in children and adolescents: the Histocompatibility and Alternate
      Stem Cell Source Working Committee of the International Bone Marrow Transplant
      Registry.
AB  - PURPOSE: Peripheral-blood stem cells (PBSC) may be used as an alternative to bone
      marrow (BM) for allogeneic transplantation. Despite lack of data on PBSC
      transplantation in children, there has been a change in clinical practice, with
      increasing numbers of children receiving PBSC allografts. PATIENTS AND METHODS:
      We compared the results of 143 PBSC and 630 BM transplants from human leukocyte
      antigen-identical sibling donors in children aged 8 to 20 years with acute
      leukemia. PBSC transplant recipients were older, and were more likely to have
      advanced leukemia, receive growth factors post-transplantation, and have
      undergone transplantation more recently. Risks of acute and chronic graft-versus
      host disease (GVHD), treatment-related mortality, relapse, treatment failure
      (relapse or death), and overall mortality were compared using Cox proportional
      hazards regression to adjust for potentially confounding factors. RESULTS:
      Hematopoietic recovery was faster after PBSC transplantation. Risks of grade 2 to
      4 acute GVHD were similar, but chronic GVHD risk was higher after PBSC
      transplantation (relative risk [RR], 1.85; 95% CI, 1.28 to 2.66; P = .001). In
      contrast to reports in adults, treatment-related mortality (RR, 1.89; 95% CI,
      1.28 to 2.80; P = .001), treatment failure (RR, 1.31; 95% CI, 1.03 to 1.68; P =
      .03), and mortality (RR, 1.38; 95% CI, 1.07 to 1.79; P = .01) were higher after
      PBSC transplantation. Risks of relapse were similar. CONCLUSION: These data
      suggest poorer outcomes after PBSC compared with BM transplantation in children
      after adjusting for relevant risk factors. Given the trend toward increased use
      of PBSC allografts in children, prospective clinical trials are required to
      determine their appropriate role in this group of patients.

PMID- 15520057
TI  - Chemotherapy for patients with hormone-refractory prostate cancer.

PMID- 15520058
TI  - Palliative chemotherapy for advanced gastric cancer.
AB  - BACKGROUND: More than two-thirds of patients diagnosed with gastric cancer will
      have unresectable disease. They present a difficult problem to clinicians as to
      whether to choose a strictly supportive approach or expose patients to the side
      effects of a potentially ineffective treatment. The objective of this article is
      to review the clinical trials utilizing cytotoxic chemotherapy in patients with
      advanced gastric cancer. METHODS: A computerized (Medline) search was carried out
      to identify papers published on this topic between 1966 and 2003. Only articles
      with an English abstract were reviewed, and studies only presented in abstract
      form were not included in the analysis. RESULTS: A total of 101 trials were
      subsequently identified. Four randomized trials compared palliative chemotherapy
      with best supportive care in 174 patients with advanced gastric cancer.
      Effectiveness and side-effects were evaluated in 73 phase II studies and 24
      randomized phase III trials. CONCLUSION: Analysis of results shows chemotherapy
      to be superior to best supportive care alone. Combination chemotherapy compared
      with monochemotherapy is associated with significantly higher overall (complete
      plus partial) response rates but nevertheless results in similar survival. ECF
      (epirubicin, cisplatin and 5-fluorouracil) currently represents one of the most
      effective regimens for advanced gastric cancer, whereas among the newer
      combinations, irinotecan- or taxane-based regimens have also given promising
      results. In patients with a poor performance status, consideration could be given
      to leucovorin-modulated 5-fluorouracil alone. Prognosis for the majority of
      patients, however, remains poor, as increases in survival were moderate at best.

PMID- 15520059
TI  - Perceptions of older people with cancer of information, decision making and
      treatment: a systematic review of selected literature.
AB  - BACKGROUND: Several studies have identified inadequacies in the care and
      treatment received by older patients with cancer, as opposed to their younger
      counterparts. These include over or under diagnosis, ineffective symptom
      management and lower survival rates in older people with cancer. Despite these
      inadequacies, there is a lack of evidence of older peoples' perspectives
      regarding their cancer diagnosis and treatment. MATERIALS AND METHODS: Studies
      for review were identified from systematic searches of literature published
      between January 1990 and November 2003, using PubMed, CINAHL and PsycINFO.
      Studies were selected for inclusion by using a number of criteria (i.e. date and
      language of publication, age of participants and thematic area). The aims of the
      review were to summarize and evaluate previous evidence on the views of older
      patients with cancer, regarding information, decision making and treatment.
      RESULTS: Eighteen studies of various methodologies met the criteria of the
      present review. In summary, older people with cancer are generally content with
      the information they receive, but not entirely satisfied with the quantity and
      quality of care and contact. They present with various needs, which are not
      always well met. Finally, they wish to be kept informed of their cancer diagnosis
      and treatment progress, but often do not wish to be told about progression of
      their illness and length of survival. CONCLUSIONS: Previous research has suffered
      a number of limitations regarding sampling procedures and methods of data
      collection. Other limitations included lack of consideration of the heterogeneity
      of older people with cancer and lack of a well-defined theoretical framework to
      guide design and data analysis. These may compromise not only rigour and the
      ability to generalize findings, but also the provision of patient-focused care.
      The difficulties of doing research in this area are also discussed and
      suggestions for future research are made.

PMID- 15520060
TI  - Recommendations for a Global Core Curriculum in Medical Oncology.

PMID- 15520061
TI  - Randomised phase III study of intravenous vinorelbine plus hormone therapy versus
      hormone therapy alone in hormone-refractory prostate cancer.
AB  - BACKGROUND: Vinorelbine (VRL) has been shown to be active in hormone-refractory
      prostate cancer (HRPC) in phase II studies, alone or in combination. Its moderate
      toxicity profile is well tolerated in elderly patients. PATIENTS AND METHODS:
      Patients with metastatic prostate cancer, progressive after primary hormonal
      therapy, were randomised to receive intravenous VRL 30 mg/m2 on days 1 and 8
      every 3 weeks, and hydrocortisone 40 mg/day or hydrocortisone alone until disease
      progression. Centres could choose to add aminoglutethimide 1000 mg/day to
      hydrocortisone as second-line hormone therapy (HT) for all their patients.
      Randomisation was stratified by centre. Further chemotherapy was allowed after
      progression. The primary end point was progression-free survival (PFS). The final
      analysis was performed on a total of 414 patients. Reported results were all
      based on intention-to-treat analyses. All progressions and responses were
      reviewed by an independent panel. RESULTS: PFS was significantly prolonged in the
      VRL plus HT arm compared with the HT alone arm, according to the statistical
      hypothesis of the protocol (P=0.055 in the two-sided log-rank test with a pre
      specified significance level of 10%). The 6-month PFS rates were 33.2% versus
      22.8%, and the median durations of PFS were 3.7 versus 2.8 months. In the
      multivariate Cox analysis, which included age, Karnofsky performance status (PS),
      haemoglobin, alkaline phosphatase at study entry and number of prior hormonal
      treatments, the P value was decreased to 0.005. The prostate-specific antigen
      (PSA) response rate (> or =50% decline sustained for at least 6 weeks) was
      significantly higher for VRL plus HT compared with HT (30.1% versus 19.2%;
      P=0.01). Clinical benefit, defined as a decrease in pain intensity or analgesic
      consumption or an improvement of Karnofsky PS for at least 9 weeks, and at least
      stable assessment in the other two, was also more frequently observed in patients
      who received VRL plus HT versus HT alone (30.6% and 19.2%; P=0.008). There was no
      statistical difference in overall survival. Forty-three per cent of patients in
      the HT arm received at least one line of further chemotherapy after progression,
      compared with 28% of patients in the VRL-based arm. Aminoglutethimide did not
      seem to result in better efficacy for either arm. VRL plus HT was well tolerated,
      with a median administered relative dose intensity of 90%; grade 4 neutropenia
      occurred in 6.5% of patients and non-haematological toxicity was rare.
      CONCLUSIONS: The combination of VRL and hydrocortisone compared with
      hydrocortisone alone resulted in improved clinical benefit, PFS and PSA response
      rate. This therapeutic gain is similar to that previously reported with
      mitoxantrone in combination with low-dose corticosteroids. There was no gain in
      survival; however, the combination is well tolerated in this elderly group of
      patients, who often present cardiac co-morbidities, and therefore offers an
      active and safe therapeutic option for patients with hormone-refractory prostate
      cancer.

PMID- 15520062
TI  - Tamoxifen-induced tissue factor pathway inhibitor reduction: a clue for an
      acquired thrombophilic state?
AB  - BACKGROUND: Current understanding of hemostatic systems enables us to better
      explore the enigmatic pathobiology of tamoxifen (TAM)-induced thrombotic
      diathesis. We have therefore aimed to assess the hemostatic changes in breast
      cancer patients receiving TAM on an adjuvant basis. PATIENTS AND METHODS: The
      study population consisted of 43 female patients with hormone receptor-positive
      breast cancer who received TAM 20 mg/day as part of their adjuvant treatment.
      Mean age was 52+/-12 years (range 25-74). Twenty-one patients (49%) were
      premenopausal. Plasma samples were collected prior to and following 6 months of
      TAM therapy and were assayed for total tissue factor pathway inhibitor (TFPI),
      free TFPI, lipid-bound TFPI, thrombomodulin, D dimer, activated protein C
      resistance (APC res), factors VIIa, II, V, VII and X, and global fibrinolytic
      capacity (GFC). RESULTS: Median total TFPI decreased significantly from 48.5
      ng/ml to 36.2 ng/ml (P=0.001), free TFPI from 10 to 7.6 ng/ml (P=0.001) and lipid
      bound TFPI from 39.1 to 28.7 ng/ml (P=0.001). There were significant decreases in
      the levels of factor II (P=0.03), factor V (P=0.001), factor VII (P=0.06),
      thrombomodulin (P=0.01) and D dimer (P=0.001). However, APC res times were
      significantly prolonged (P=0.04). The remaining parameters that we have studied
      were not significantly affected. CONCLUSION: Our findings suggest that TAM tends
      to activate the coagulation pathway by counteracting major molecules involved in
      coagulation inhibition, namely TFPI and TM. As reflected by unchanged GFC, the
      drug appears to impair the expected compensatory activation of the fibrinolytic
      system, which removes fibrin polymers resulting from coagulation activation.

PMID- 15520063
TI  - Micrometastatic bone marrow cells at diagnosis have no impact on survival of
      primary breast cancer patients with extensive axillary lymph node involvement
      treated with stem cell-supported high-dose chemotherapy.
AB  - BACKGROUND: To determine the impact of micrometastatic bone marrow cells (MMC) on
      survival in high-risk primary breast cancer (HRPBC) patients treated with high
      dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT).
      PATIENTS AND METHODS: Ninety-one HRPBC patients (73 patients with > or =10
      involved axillary lymph nodes (ALN), 18 premenopausal women with > or =4 involved
      ALN) received one cycle (eight patients) or two cycles of HDCT and ASCT. Bone
      marrow aspiration was performed before systemic treatment to search for MMC using
      a cocktail of four monoclonal epithelial-specific antibodies (5D3, HEA125, BM7
      and BM8). The influence of MMC and other prognostic factors on disease-free
      survival (DFS), distant DFS (DDFS), and overall survival (OS) was analysed.
      RESULTS: In 23 of 91 patients (25%) we detected a median of three MMC (range, 1
      43) among 10(6) mononuclear cells. With a median follow-up of 62 months (range,
      10-117), the detection of MMC was not associated with DFS (P=0.929), DDFS
      (P=0.664) or OS (P=0.642). In multivariate analysis the strongest predictor was
      nodal ratio for DFS (P=0.012) and expression of p53 for OS (P <0.001).
      CONCLUSION: The detection of MMC at diagnosis has no impact on survival in HRPBC
      patients treated with HDCT and ASCT.

PMID- 15520064
TI  - Minimal and small size invasive breast cancer with no axillary lymph node
      involvement: the need for tailored adjuvant therapies.
AB  - BACKGROUND: Prognosis of patients with node-negative disease and tumor size <1 cm
      is a matter of controversy. While data exist to clearly correlate small tumor
      size to better prognosis, the fact that very small breast cancers may express
      biological markers of dire prognosis leads many to ignore small tumor size during
      treatment decision-making. PATIENTS AND METHODS: Data from 425 patients
      classified as having node-negative pT1mic, pT1a or pT1b after surgery (from April
      1997 to December 2001) at the European Institute of Oncology, were analyzed to be
      described as disease-free according to prognostic variables including: Ki-67
      (<20% versus > or =20% of the cells), ER (absent versus positive > or =1% of the
      cells), PgR (absent versus positive > or =1% of the cells), grade, overexpression
      or amplification of HER2/neu, presence of peritumoral vascular invasion and age
      (by decade). The median follow-up for this cohort of patients was 43 months.
      RESULTS: No local or distant relapse was observed for patients with pT1mic breast
      cancer; 4-year disease-free survival for pT1a and pT1b was 97.0% and 97.6%,
      respectively. In both univariate and multivariate analyses the most relevant
      prognostic factor for this low-risk population was Ki-67 labeling. The 4-year
      disease-free survival was 99.2% for tumors with low Ki-67 and 93.3% for tumors
      with high Ki-67 (> or =20%) labeling. The hazard ratio (HR) for patients with
      high Ki-67 was 12.9 (95% CI 1.5-112.0, P=0.02). CONCLUSIONS: Within the first 4
      years, microinvasive breast cancer parallels ductal carcinoma in situ (DCIS)
      rather than invasive carcinoma. Costs and benefits of adjuvant therapy should be
      accurately weighted in these patients. Patients with pT1a and pT1b, node-negative
      disease have a limited but substantial risk of recurrence and therefore adjuvant
      therapy, according to endocrine responsiveness of the tumor and patient
      preference, should continue to be offered as a reasonable treatment option.

PMID- 15520065
TI  - Risk factors for brain relapse in patients with metastatic breast cancer.
AB  - BACKGROUND: The occurrence of brain metastases is an emerging problem in patients
      with metastatic breast cancer. In the present study, we looked at risk factors
      for brain metastasis among patients with metastatic breast cancer. PATIENTS AND
      METHODS: The risk factors for brain metastasis were first determined in a series
      of 215 patients with metastatic breast cancer. Risk factors identified in the
      multivariate analysis were re-evaluated in a confirmatory series of 199 patients
      with metastatic breast cancer. All the patients had been included in prospective
      randomized trials that evaluated chemotherapy or endocrine therapy in an adjuvant
      setting. RESULTS: In the first series, the presence of lung metastases (hazard
      ratio = 4.3, 95% CI: 1.9-9.3, P=0.0003) and negative hormone receptor status
      (hazard ratio = 4.2, 95% CI: 1.7-11, P=0.002) were the only predictive factors
      associated with the occurrence of brain metastases in the multivariate analysis.
      The second series confirmed that the presence of lung metastases and negative
      hormone receptor status were associated with the occurrence of brain metastases.
      CONCLUSION: The presence of lung metastases as the first site of relapse and a
      negative hormone receptor status are predictive for the occurrence of brain
      metastases in patients with metastatic breast cancer. A prophylactic treatment
      should be evaluated in these subsets of patients.

PMID- 15520066
TI  - Long-term survival of surgically staged IIIA-N2 non-small-cell lung cancer
      treated with surgical combined modality approach: analysis of a 7-year
      prospective experience.
AB  - BACKGROUND: The aim of this study was to analyse the outcome of surgically staged
      IIIA-N2 non-small-cell lung cancer (NSCLC) treated with induction chemotherapy
      followed by surgical exploration. METHODS: Univariate and multivariate analyses
      were carried out on a prospective cohort of 131 mediastinoscopy-proven IIIA-N2
      NSCLC patients. Three preoperative cycles of vindesine-ifosfamide-cisplatin (VIP)
      were given. Patients with at least stable disease (SD) were considered for
      surgery, or radical radiotherapy in selected cases. RESULTS: The response rate
      after VIP was 54% (95% confidence interval 45% to 63%) and was important for the
      final outcome. The median and 5-year survival for the total group were 24 months
      and 21% (38 months and 30% in responders), respectively. Involvement of
      subcarinal nodes at diagnosis was the most important prognostic factor (P=0.022).
      Seventy-five patients were considered for surgery. Downstaging occurred in 34 of
      70 resection specimens, with a pathological complete response in six. Median and
      5-year survival in the surgical cohort were 45 months and 35%, respectively.
      Surgery was rewarding both in patients with a response and in those with SD,
      although the complete resection rate was significantly lower in the latter. On
      multivariate analysis, favourable prognostic factors were low pathological T
      stage (P=0.001) and downstaging of mediastinal nodes in the resection specimen
      (P=0.008). CONCLUSIONS: VIP induction chemotherapy followed by surgical
      exploration was rewarding in mediastinoscopy-proven stage IIIA-N2 NSCLC, both in
      cases of response and SD, despite a lower complete resection rate in the latter.
      Patients with subcarinal nodes at diagnosis (5-year survival 8.5%) or without
      nodal downstaging at post-induction surgery (13.7%) might preferably be treated
      with a non-surgical approach.

PMID- 15520067
TI  - Nuclear localization of survivin is a positive prognostic factor for survival in
      advanced non-small-cell lung cancer.
AB  - BACKGROUND: Expression of survivin, a member of the inhibitor of apoptosis
      protein family, is commonly detected in cancers but not in normal differentiated
      tissues. Survivin is usually localized in the cytoplasm of cancer cells, but
      nuclear localization has also been described, and we recently reported that
      survivin is a nuclear-cytoplasmic shuttling protein. PATIENTS AND METHODS: Fifty
      three tumor specimens from patients with inoperable non-small-cell lung cancer
      (NSCLC) (55% stage IIIA, 17% stage IIIB and 28% stage IV) who underwent
      chemotherapy treatment were evaluated with immunohistochemistry for survivin
      expression and localization. These two sets of data were processed and tested for
      correlation with major patient characteristics, response to chemotherapy, and
      overall and relapse-free survival. RESULTS: Survivin was present only in
      malignant tissues, and 47/53 (89%) of the specimens were positive. The overall
      median expression of tumor cells was 40%, and this value was used as a cut-off
      point for statistical analysis. By dichotomizing the specimens as expressing low
      or high levels of survivin, a significant association was seen between the
      expression of survivin and the histology of the tumors (P=0.020), squamous cell
      carcinoma being the histotype with lower levels of survivin expression. Three
      patterns of localization were observed: 42% of cases (22/53) showed reactivity
      confined to the nucleus, 17% (nine of 53) only in the cytoplasm and 30% (16/53)
      in both the nucleus and the cytoplasm. Interestingly, nuclear survivin levels
      predicted longer overall and relapse-free survival, in univariate and
      multivariate analyses. Expression and localization of survivin did not correlate
      with response to chemotherapy. CONCLUSIONS: Our results indicate that
      differential localization of survivin may be a prognostic factor for NSCLC.
      Further studies are warranted.

PMID- 15520068
TI  - Hepatitis B reactivation in patients with hepatocellular carcinoma undergoing
      systemic chemotherapy.
AB  - BACKGROUND: Cancer patients who are hepatitis B virus (HBV) carriers and
      undergoing chemotherapy (CT) may be complicated by HBV reactivation. Over 80% of
      hepatocellular carcinoma (HCC) patients are HBV carriers; however, the incidence
      of HBV reactivation during CT has not been well-reported. A prospective study was
      conducted to determine the incidence of HBV reactivation, the associated
      morbidity and mortality, and possible risk factors. PATIENTS AND METHODS: 102
      HBsAg-positive patients with inoperable HCC underwent systemic CT. Patients
      received either combination cisplatin, interferon, doxorubicin and fluorouracil
      (PIAF) or single-agent doxorubicin. They were followed up during and for 8 weeks
      after CT. RESULTS: In 102 patients, 59 (58%) developed hepatitis amongst whom 37
      (36%) were attributable to HBV reactivation. Twelve (30%) died of HBV
      reactivation. CT was interrupted in 32 patients (86%) with reactivation and 54
      (83%) without reactivation (P>0.05). The median survivals were 6.00 and 5.62
      months, respectively (P=0.694). Elevated baseline alanine aminotransferase (ALT)
      was found to be a risk factor. CONCLUSION: HBV reactivation is a common cause of
      liver damage during CT in HBsAg-positive HCC patients. The only identifiable
      associated risk factor was elevated pre-treatment ALT. Further studies into the
      role of antiviral and novel anticancer therapies are required to improve the
      prognosis of these patients.

PMID- 15520069
TI  - Neo-adjuvant chemotherapy for primary high-grade extremity soft tissue sarcoma.
AB  - BACKGROUND: The purpose of this study was to retrospectively analyze the
      relationship between neo-adjuvant chemotherapy (NAC) and outcome in patients with
      high-grade extremity sarcomas. PATIENTS AND METHODS: Inclusion criteria were high
      grade, deep, >5 cm extremity soft tissue sarcomas. Patients diagnosed between
      1990 and 2001 were treated with surgery only (n=282) or NAC containing
      doxorubicin/ifosfamide/mesna (AIM) (n=74). The stratified Cox proportional
      hazards model was used to test the effect of NAC on disease-specific survival and
      recurrence while adjusting for known prognostic factors. RESULTS: NAC was
      associated with improved disease-specific survival for this cohort of patients
      (P=0.02). This overall improvement appears to be driven by the benefit of NAC on
      disease-specific survival for patient with tumors >10 cm. The 3-year disease
      specific survival for tumors >10 cm was 0.62 (95% CI: 0.53-0.71) for patients not
      receiving NAC and 0.83 (95% CI: 0.72-0.95) for patients receiving NAC.
      CONCLUSION: NAC with AIM was associated with a significant improvement in disease
      specific survival in patients with high-grade extremity soft tissue sarcomas >10
      cm. These data emphasize the need for further prospective clinical studies of neo
      adjuvant or adjuvant chemotherapy for patients with large high-grade extremity
      sarcomas.

PMID- 15520070
TI  - CD20-negative large-cell lymphoma with plasmablastic features: a clinically
      heterogenous spectrum in both HIV-positive and -negative patients.
AB  - BACKGROUND: Plasmablastic lymphoma (PBL) has been described as a rapidly
      progressive and almost invariably fatal CD20- VS38c+ diffuse large-cell lymphoma
      with plasmablastic features, almost exclusively involving the jaw and oral mucosa
      in HIV-positive patients. METHODS: From 2001 to 2003 we evaluated 12 men with
      PBL, and report the pathology, clinical findings, treatment and outcome. Six of
      12 were HIV-positive while among the others, one was post-renal transplant, one
      had ulcerative colitis and four had no known immunodeficiency. RESULTS: Tumor
      growth pattern, in general, showed cohesiveness and a starry-sky pattern; the
      morphology varied from typical plasmablastic to centroblastic cells. Partial
      immunophenotypes were (+/total): CD138, 11 of 12 (91.7%); MIB1 10 of 11 (4+,
      range 75-95%); p63/VS38c, nine of 10 (90%); EBV, eight of 11 (73%); LCA(CD45),
      two of 12 (16.7%); HHV8/LANA, zero of 10; ALK, zero of seven; and CD20, zero of
      12. Three had stage IE and nine stage IV disease. Nine of 12 had an
      intermediate/high International Prognostic Index or high-risk disease. Computed
      tomography and positron emission tomography scan in four of 12 revealed extensive
      bone metastases. Eight of 12 are alive after treatment, with a median follow-up
      of 11+ months (range 1-24). Of the HIV-positive patients, five of six are alive
      with a median follow-up of 17 months. CONCLUSIONS: It appears that PBL are
      heterogenous in terms of clinical presentation and morphology. The outcome
      presented here is superior to that originally reported.

PMID- 15520071
TI  - Chemotherapy with cyclophosphamide, doxorubicin, etoposide, vincristine and
      prednisone (CHOEP) is not effective in patients with enteropathy-type intestinal
      T-cell lymphoma.
AB  - BACKGROUND: Enteropathy-type intestinal T-cell lymphoma (ETCL) is a highly
      aggressive disease with poor response to conventional CHOP (cyclophosphamide,
      doxorubicin, vincristine and prednisone) chemotherapy. According to promising
      data with the addition of etoposide (E) to the CHOP regimen (CHOEP) in aggressive
      lymphomas including T-cell lymphomas, we have treated patients with ETCL with
      CHOEP chemotherapy. PATIENTS AND METHODS: Ten consecutive patients (six female,
      four male) suffering from ETCL were given CHOEP at our institution. Four patients
      had advanced disease (stage III/IV), while five patients were rated to be in
      stage II and one in stage I. Treatment consisted of doxorubicin 50 mg/m2,
      cyclophosphamide 750 mg/m2 and vincristine 1.4 mg/m2 by intravenous infusion on
      day 1, etoposide 100 mg/m2 intravenously days 1-3 and oral prednisone days 1-5.
      Cycles were repeated every 3 weeks for a maximum of six courses. Assessment of
      response was done by means of conventional computed tomography scanning,
      endoscopy and also [18F]fluorodeoxyglucose positron emission tomography (FDG PET)
      in seven patients. RESULTS: A total of 41 cycles (median six, range one to six)
      were administered to our patients. Leukocytopenia/neutropenia WHO grade IV
      necessitating granulocyte colony-stimulating factor support occurred in all
      patients evaluable for toxicity, and febrile neutropenia was seen in two
      patients. Two patients had to undergo emergency surgery due to intestinal
      perforation after one and three courses of treatment, respectively. Therapeutic
      results, however, were disappointing: two patients had complete remission (CR),
      three had partial remissions and five patients progressed during treatment.
      Remissions, however, where only short-lasting, as only two patients are alive at
      a median follow-up of 7 months (range 2-16). One patient is in ongoing CR 10
      months after initiation of chemotherapy and the other is currently undergoing
      second-line treatment for progressive disease as judged by follow-up
      investigations after three cycles of CHOEP. CONCLUSIONS: Our data demonstrate
      that CHOEP chemotherapy results in a high rate of hematotoxicity in patients with
      ETCL. In spite of this, therapeutic results were disappointing and do not appear
      to be superior to conventional CHOP chemotherapy. We conclude that CHOEP cannot
      be recommended for routine use in patients with ETCL.

PMID- 15520072
TI  - Once-weekly dosing of recombinant human erythropoietin alpha in patients with
      myelodysplastic syndromes unresponsive to conventional dosing.
AB  - BACKGROUND: Once-weekly dosing of recombinant human erythropoietin (rhEPO) in
      patients with myelodysplastic syndromes (MDS) has not been investigated
      thoroughly. We performed a clinical trial to evaluate the effects of this new
      dosing regimen in patients with MDS who were unresponsive to the conventional
      three-times-weekly schedule. PATIENTS AND METHODS: Forty-eight patients with low-
      or intermediate-risk MDS were enrolled in a 12-week study. rhEPO alpha
      (rhEPOalpha) was administered once-weekly by subcutaneous injection with a
      starting dose of 40,000 U fixed dose. The drug dosage was increased to 60,000 U
      fixed dose if after 6 weeks there was no or suboptimal erythroid response.
      RESULTS: Clinically significant responses were seen in 13 (27%) patients, with 11
      improving their response after dose escalation of rhEPOalpha. Only one patient
      (case 23) maintains a response after a follow-up period of 14 months. All other
      patients had responses lasting between 10 and 43 weeks, with a median time to
      relapse of 20 weeks. Treatment was well tolerated, with no relevant adverse
      events. Response to therapy was associated with significantly higher
      concentrations of circulating erythroid blast-forming units and a decrease of the
      bone marrow fraction of apoptic CD34+ cells. CONCLUSIONS: Once-weekly rhEPOalpha
      therapy results in an improvement of erythropoiesis in a subset of MDS patients
      who are unresponsive to conventional dosing, and may act by inhibiting apoptosis
      of erythroid precursors. These results warrant further investigation of this
      dosing regimen either alone or in combination with other agents.

PMID- 15520073
TI  - Rituximab consolidation after high-dose chemotherapy and autologous blood stem
      cell transplantation in follicular and mantle cell lymphoma: a prospective,
      multicenter phase II study.
AB  - BACKGROUND: Patients with follicular (FL) or mantle cell lymphoma (MCL) are
      incurable with conventional therapy. We investigated the safety and efficacy of
      rituximab consolidation after autologous stem cell transplantation (ASCT) in
      order to prevent relapse by clearance of minimal residual disease (MRD). METHODS:
      Rituximab was given approximately 8 weeks after CD34+ cell enriched ASCT at 375
      mg/m2, weekly for 4 weeks. Monitoring of MRD was performed by repetitive PCR
      analyses. RESULTS: Thirty-one patients were included; one died early after ASCT
      before rituximab administration. Thirty patients (20 FL, 10 MCL) were evaluable
      after rituximab consolidation, and 27 of these were assessable for MRD detection.
      Rituximab consolidation post-ASCT was safe, the most common toxicity being
      infection. At a median follow-up of 42 months (range 13-96) after ASCT, 25
      patients were censored with an actuarial event-free survival (EFS) of 81% at 4
      and 5 years. Four patients (two FL, two MCL) relapsed, and one additional MCL
      patient died unexpectedly in complete remission. PCR-negativity was observed in
      22% of the patients before ASCT, 53% post-ASCT (P=0.0547), 72% after rituximab
      (P=0.0018) and 100% at 6 months post-transplant (P < 0.001). CONCLUSIONS: One
      single course of rituximab consolidation given after ASCT is safe, may help to
      eliminate MRD and may translate into improved EFS in both FL and MCL patients.

PMID- 15520074
TI  - Contribution of PET imaging to the initial staging and prognosis of patients with
      Hodgkin's disease.
AB  - BACKGROUND: Positron emission tomographic (PET) scanning utilizing
      [18F]fluorodeoxyglucose (FDG) is a new method of tumor imaging based on the
      increased glucose metabolic activity of malignant tumors. In Hodgkin's disease
      (HD), PET has proven value for the evaluation of residual masses following
      treatment and for the early diagnosis of relapse. In the initial staging of HD,
      PET frequently shows a higher stage than conventional methods (upstaging by PET).
      In the present study, we evaluated the frequency of stage changes by PET in a
      multicenter setting and determined its prognostic relevance. PATIENTS AND
      METHODS: A total of 73 patients with newly diagnosed HD were staged with both
      conventional methods and whole-body PET scanning. All histological types and
      stages were represented. The median time of follow-up after the initial diagnosis
      was 25 months (range 1 month to 5 years). The response to treatment was
      determined by standard clinical and diagnostic criteria. For the purpose of this
      analysis, data from a PET center associated with a university medical center and
      a PET center associated with a group oncology practice were combined. RESULTS: A
      total of 21 patients (28.8%) were upstaged by PET compared with conventional
      methods. In two cases (2.7%), a lower stage was suggested by PET scanning. With
      one possible exception, the upstaging had no obvious clinical or biological
      correlate. Among 12 patients in stage I (A + B) by conventional methods, seven
      were upstaged by PET (58.3%), four to stage II, one to stage III and two to stage
      IV. Among 42 patients in stage II, eight were upstaged by PET (19.0%), six to
      stage III and two to stage IV. Among 12 patients in stage III, six (50%) were
      upstaged to stage IV by PET. If only early-stage patients and major changes are
      considered (stages IA-IIB to III or IV), among 49, 10 were upstaged to III or IV,
      whereas in 39 staging was unchanged following PET. In the former group, three
      relapsed or were refractory compared with none in the latter group (P<0.006). In
      advanced stage patients (IIIA or IIIB) a trend toward treatment failure was
      apparent in patients who were upstaged by PET. CONCLUSIONS: PET scanning is an
      interesting new modality for the accurate staging of patients with HD and
      frequently shows a higher stage than conventional methods. PET should be
      performed at initial diagnosis and should be included in prospective studies of
      patients with HD. Upstaging by PET may represent a risk factor for a more
      advanced stage or a biologically more aggressive tumor. Patients with early-stage
      disease as identified by conventional methods have a significant risk of
      treatment failure if a more advanced stage is indicated by PET. At present, major
      stage changes suggested by PET imaging should be confirmed by an independent
      diagnostic method.

PMID- 15520075
TI  - A phase I study of the oral combination of CI-994, a putative histone deacetylase
      inhibitor, and capecitabine.
AB  - BACKGROUND: This study was conducted to determine the toxicity profile, maximum
      tolerated dose (MTD) and pharmacokinetics of the putative histone deacetylase
      inhibitor CI-994 in combination with capecitabine. PATIENTS AND METHODS: Fifty
      four patients were treated according to three different dosing schemes in which
      the capecitabine dose was fixed and the CI-994 dose was escalated. Capecitabine
      was administered in twice daily divided doses, and CI-994 was given as a single
      daily dose. In schedule A, 26 patients were treated with capecitabine 1650
      mg/m2/day and CI-994 for 2 weeks of a 3-week cycle. In schedule B, six patients
      received capecitabine 1650 mg/m2/day for two 3-week cycles and CI-994 for 5 of 6
      weeks. In schedule C, 22 patients were treated with capecitabine 2000 mg/m2/day
      and CI-994 for 2 of 3 weeks. RESULTS: At the MTD, the principal dose-limiting
      toxicity was thrombocytopenia. The pharmacokinetics of CI-994 were unaltered by
      capecitabine, and there was no correlation between body surface area and major
      pharmacokinetic parameters. Platelet count nadir was best predicted by the
      observed maximal concentration (C(max)) of CI-994. CONCLUSIONS: The recommended
      phase II dose is 6 mg/m2 (or 10 mg) of CI-994 in combination with capecitabine
      2000 mg/m2/day for 2 weeks of a 3-week cycle.

PMID- 15520076
TI  - Trends in cancer mortality in Mexico, 1970-1999.
AB  - BACKGROUND: Few data on cancer mortality have been published for Mexico over the
      last few decades. It is therefore of interest to conduct a systematic and updated
      analysis of cancer mortality in this country. PATIENTS AND METHODS: Age
      standardised (world population) mortality rates, at all ages and truncated at age
      35-64 years, from major cancers and all cancers combined were computed on the
      basis of certified deaths derived from the World Health Organization database for
      the period 1970-99. RESULTS: Mortality rates for all neoplasms showed an upward
      trend in men of all ages (from 58.2/100,000 in 1970-74 to 87.1/100,000 in 1995
      99) and in middle-aged men (from 76.1 to 93.7/100,000, respectively). This
      reflects the rise until the early 1990s in lung cancer mortality (from
      8.1/100,000 in 1970-74 to 15.6/100,000 in 1995-99) and prostate cancer (from 5.5
      to 12.2/100,000, respectively). In women, overall mortality rates showed an
      increase between the early 1970s (75.4/100,000) and the late 1990s
      (82.3/100,000). Total cancer mortality rates remained low, however, compared with
      other American countries (e.g. 153.3/100,000 men and 108.6/100,000 women in 1999
      in the United States). Truncated rates were stable (126.5/100,000 in 1970-74 and
      125.8/100,000 in 1995-99), although they were much higher than overall rates,
      reflecting exceedingly high rates for uterine (mostly cervical) cancer mortality
      in middle-aged women (29.5/100,000 in 1995-99). CONCLUSIONS: Total cancer
      mortality in Mexico has remained comparably low on a worldwide scale, and the
      upward trends in mortality rates for lung and other tobacco-related neoplasms
      have tended to level off over the last decade. However, steady rises have been
      observed for other major cancers, including prostate and breast. Cervical cancer
      remains a major health problem in women.

PMID- 15520077
TI  - Dietary fatty acids regulate the activation status of Her-2/neu (c-erbB-2)
      oncogene in breast cancer cells.

PMID- 15520079
TI  - Expression of Cox-2 protein in radioresistant laryngeal cancer.

PMID- 15520080
TI  - Insurance for independent cancer trials.

PMID- 15520081
TI  - t(14;18) and bcl-2 should not be used synonymously.

PMID- 15520082
TI  - Trimethoprim/sulfamethoxazole: clinical update.

PMID- 15520083
TI  - What's new in pediatric cardiology.

PMID- 15520084
TI  - Neonatal cholestasis.

PMID- 15520085
TI  - Index of suspicion.

PMID- 15520086
TI  - Are clinical impressions of adolescent substance use accurate?
AB  - OBJECTIVE: To compare providers' impressions of adolescents' level of substance
      use with diagnostic classifications from a structured diagnostic interview.
      METHODS: Secondary analysis of data was conducted from a validation study of the
      CRAFFT substance abuse screening test of 14- to 18-year-old medical clinic
      patients (n = 533) and their corresponding medical care providers (n = 109) at an
      adolescent clinic affiliated with a large tertiary care pediatric hospital.
      Medical care providers completed a form that recorded their clinical impressions
      of patients' level of alcohol and drug involvement (none, minimal, problem,
      abuse, dependence) and demographic characteristics. The form included brief
      diagnostic descriptions for each level of use. After the medical visit, patients
      completed the Adolescent Diagnostic Interview (ADI), a structured diagnostic
      interview that yields diagnoses of abuse and dependence according to the
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV).
      On the basis of their past 12 months of alcohol and drug use on the ADI
      interview, adolescents were classified into 5 mutually exclusive diagnostic
      groups. "None" was defined by no reported use of alcohol or drugs during the past
      year. "Minimal use" was defined as use of alcohol or drugs but no report of any
      substance-related problems. "Problem use" was defined as reporting 1 or more
      substance-related problems but no diagnosis of abuse or dependence. "Abuse" was
      defined by meeting any 1 of 4 DSM-IV diagnostic criteria for either alcohol or
      drug abuse but no diagnosis of dependence. "Dependence" was defined by meeting
      any 3 of 7 diagnostic criteria for either alcohol or drug dependence, with or
      without a diagnosis of abuse. Proportions were compared using Fisher exact test.
      Agreement was assessed with the weighted kappa, and these analyses were
      stratified by substance used (ie, alcohol vs drug) and demographic
      characteristics. Sensitivity, specificity, and positive and negative predictive
      values were calculated from 2 x 2 tables. RESULTS: Compared with the criterion
      standard interview, providers identified significantly fewer patients with
      problem use and abuse and no patients with dependence. Of >100 patients whom the
      ADI classified with substance problem use, providers correctly identified 18. Of
      50 patients who were classified with a diagnosis of alcohol or drug abuse,
      providers correctly identified 10. Of 36 patients who were classified with a
      diagnosis of alcohol or drug dependence, providers correctly identified none. For
      the 86 adolescents who were classified with a substance-related disorder (ie,
      abuse or dependence), providers' impressions were "none" (24.4%), "minimal use"
      (50%), "problem use" (15.1%), "abuse" (10.5%), and "dependence" (0%). There was
      only marginal agreement between providers' impressions and diagnoses related to
      alcohol use (kappa = .29), drug use (kappa = .31), and any substance use (kappa =
      .30). Kappa was not significantly affected by the patient's age, but it was by
      gender. Among boys, kappa was significantly higher for impressions of drug use
      versus alcohol use (kappa = .48 vs kappa = .27); and, among drug users, kappa was
      significantly higher among boys compared with girls (kappa = .48 vs kappa = .24).
      Kappa did not differ significantly across race/ethnicity subgroups, although
      there is a suggestive trend toward higher agreement for black non-Hispanic
      compared with white non-Hispanic adolescents (kappa = .35 vs kappa = .21). Kappa
      did not differ significantly on the basis of the visit type, but the size of this
      difference (kappa = .36 vs kappa = .24) suggests that the longer well-child visit
      yielded greater identification of substance-related pathology. Providers'
      impressions had a sensitivity of .63 for identifying use of alcohol or drugs.
      However, sensitivity was poor for identification of problem use (.14), abuse
      (.10), and dependence (0), whereas specificity and positive predictive values
      were high. Of the 86 adolescents with a diagnosis of abuse or dependence, 75.6%
      were correctly identified by providers as using substances; however, the level of
      use in 50% of these adolescents was reported by providers as minimal.
      CONCLUSIONS: In this study, clinical impressions of adolescents' alcohol/drug
      involvement underestimated substance-related pathology. When providers thought
      that use was present, there was a very high likelihood that a problem or disorder
      existed. The use of structured screening devices would likely improve
      identification of adolescents with substance-related pathology in primary care
      settings and should be considered for use with all adolescent patients, rather
      than only those who are perceived to be at higher risk.

PMID- 15520087
TI  - Health-related quality of life in children and adolescents who have a diagnosis
      of attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: The aim of treatment for attention-deficit/hyperactivity disorder
      (ADHD) is to decrease symptoms, enhance functionality, and improve well-being for
      the child and his or her close contacts. However, the measurement of treatment
      response is often limited to measuring symptoms using behavior rating scales and
      checklists completed by teachers and parents. Because so much of the focus has
      been on symptom reduction, less is known about other possible health problems,
      which can be measured easily using health-related quality-of-life (HRQL)
      questionnaires, which are designed to gather information across a range of health
      domains. The aim of our study was to measure HRQL in a clinic-based sample of
      children who had a diagnosis of ADHD and consider the impact of 2 clinical
      factors, symptom severity and comorbidity, on HRQL. Our specific hypotheses were
      that parent-reported HRQL would be poorer in children with ADHD than in normative
      US and Australian pediatric samples, in children with increasing severity of ADHD
      symptoms, and in children who had diagnoses of comorbid psychiatric disorders.
      METHODS: Cross-sectional survey was conducted in British Columbia, Canada. The
      sample included 165 respondents of 259 eligible children (63.7% response rate)
      who were referred to the ADHD Clinic in British Columbia between November 2001
      and October 2002. Children who are seen in this clinic come from all parts of the
      province and are diverse in terms of socioeconomic status and case mix. ADHD was
      diagnosed in 131 children, 68.7% of whom had a comorbid psychiatric disorder.
      Some children had >1 comorbidity: 23 had 2, 5 had 3, and 1 had 4. Fifty-one
      children had a comorbid learning disorder (LD), 45 had oppositional defiant
      disorder or conduct disorder (ODD/CD), and 27 had some other comorbid diagnosis.
      The mean age of children was 10 years (standard deviation: 2.8). Boys composed
      80.9% (N = 106) of the sample. We used the 50-item parent version of the Child
      Health Questionnaire to measure physical and psychosocial health. Physical
      domains include the following: physical functioning (PF), role/social limitations
      as a result of physical health (RP), bodily pain/discomfort (BP), and general
      health perception (GH). Psychosocial domains include the following: role/social
      limitations as a result of emotional-behavioral problems (REB), self-esteem (SE),
      mental health (MH), general behavior (BE), emotional impact on parent (PTE), and
      time impact on parents (PTT). A separate domain measures limitations in family
      activities (FA). There is also a single-item measure of family cohesion (FC).
      Individual scale scores and summary scores for physical (PhS) and psychosocial
      health (PsS) can be computed. Symptom severity data (parent and teacher) came
      from the Child/Adolescent Symptom Inventory 4. These checklists provide
      information on symptoms for the 3 ADHD subtypes (inattentive, hyperactive, and
      combined). Each child underwent a comprehensive psychiatric assessment by 1 of 4
      child psychiatrists. Documentation included a full 5-axis Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition diagnosis on the basis of
      a comprehensive assessment. Clinical information for each child was extracted
      from hospital notes. RESULTS: Compared with both population samples, children
      with ADHD had comparable physical health but clinically important deficits in
      HRQL in all psychosocial domains, FA, FC, and PsS, with effect sizes as follows:
      FC = -0.66, SE = -0.90, MH = -0.97, PTT = -1.07, REB = -1.60, BE = -1.73, PTE = 
      1.87, FA = -1.95, and PsS = -1.98. Poorer HRQL for all domains of psychosocial
      health, FA, and PsS correlated significantly with more parent-reported
      inattentive, hyperactive, and combined symptoms of ADHD. Children with > or =2
      comorbid disorders differed significantly from those with no comorbidity in most
      areas, including RP, GH, REB, BE, MH, SE, PTT, FA, and PsS, and from those with 1
      comorbid disorder in 3 domains, including BE, MH, and FA and the PsS. The mean
      PsS score for children in the ODD/CD group (mean difference: -12.9; effect size =
      -1.11) and children in the other comorbidity group (-9.0; effect size = -.77) but
      not children in the LD group were significantly lower than children with no
      comorbid disorder. Predictors of physical health in a multiple regression model
      included child's gender (beta = .177) and number of comorbid conditions (beta = 
      .197). These 2 variables explained very little variation in the PhS. Predictors
      of psychosocial health included the number of comorbid conditions (beta = -.374)
      and parent-rated combined ADHD symptoms (beta = -.362). These 2 variables
      explained 31% of the variation in the PsS. CONCLUSIONS: Our study shows that ADHD
      has a significant impact on multiple domains of HRQL in children and adolescents.
      In support of our hypotheses, compared with normative data, children with ADHD
      had more parent-reported problems in terms of emotional-behavioral role function,
      behavior, mental health, and self-esteem. In addition, the problems of children
      with ADHD had a significant impact on the parents' emotional health and parents'
      time to meet their own needs, and they interfered with family activities and
      family cohesion. The differences that we found represent clinically important
      differences in HRQL. Our study adds new information about the HRQL of children
      with ADHD in relation to symptom severity and comorbidity. Children with more
      symptoms of ADHD had worse psychosocial HRQL. Children with multiple comorbid
      disorders had poorer psychosocial HRQL across a range of domains compared with
      children with none and 1 comorbid disorder. In addition, compared with children
      with no comorbidity, psychosocial HRQL was significantly lower in children with
      ODD/CD and children in the other comorbidity group but not in children with an
      LD. The demonstration of a differential impact of ADHD on health and well-being
      in relation to symptom severity and comorbidity has important implications for
      policies around eligibility for special educational and other supportive
      services. Because the impact of ADHD is not uniform, decisions about needed
      supports should incorporate a broader range of relevant indicators of outcome,
      including HRQL. Although many studies focus on measuring symptoms using rating
      scales and checklists, in our study, using a multidimensional questionnaire, we
      were able to show that many areas of health are affected in children with ADHD.
      We therefore argue that research studies of children with ADHD should include
      measurement of these broader domains of family impact and child health.

PMID- 15520088
TI  - Palivizumab use in very premature infants in the neonatal intensive care unit.
AB  - OBJECTIVE: The purpose of this study was to determine the ability of young
      hospitalized premature (born < or =30 weeks' gestational age) infants to achieve
      serum levels of palivizumab that are protective against RSV infection. METHODS:
      Palivizumab, 15 mg/kg per dose intramuscularly, was administered every 28 days to
      stable premature infants who were hospitalized in the neonatal intensive care
      unit starting at 1 month of postnatal life. Palivizumab concentrations were
      assayed in serum samples that were drawn from infants who remained in the
      hospital at 14 days (midpoint concentration) and at 28 days (trough
      concentration) after each dose was administered. RESULTS: The gestational age of
      the 24 infants who were enrolled was 27.5 +/- 1.8 weeks (mean +/- standard
      deviation), and birth weight was 928 +/- 159 g. Midpoint palivizumab
      concentrations in the 24 infants after the first dose were 45.6 +/- 13.0
      microg/mL; 71% (17 of 24) of the infants maintained optimal palivizumab
      concentrations (> or =40 microg/mL). The concentrations dropped subsequently;
      trough concentrations just before the second dose were 32.2 +/- 10.5 microg/mL,
      and only 23% (5 of 22) of the infants had concentrations in the optimal range.
      Sixteen infants were given 2 doses and 6 were given three doses of palivizumab
      while in the neonatal intensive care unit. Midpoint concentrations after the
      second dose were significantly higher than those after the first dose. Likewise,
      trough concentrations before the third dose were 51.9 +/- 7.8 microg/mL and
      higher than those before the second dose; the concentrations were >40 microg/ml
      in all 6 infants tested. CONCLUSIONS: Very premature infants had sustained
      optimal protective serum concentrations only after the second dose of
      palivizumab; 77% of infants tested had trough concentrations <40 microg/mL before
      the second dose. Additional studies are needed to establish the optimal timing of
      the initial dose and optimal dosing interval of palivizumab in this most
      vulnerable population.

PMID- 15520089
TI  - "Who is sitting across from me?" Immigrant mothers' knowledge of parenting and
      children's development.
AB  - OBJECTIVE: Although parents' knowledge about child development and child rearing
      is relevant to pediatric practice, very little is known about immigrant parents'
      knowledge. To fill this gap in research, this study investigated parenting
      knowledge in 2 groups of mothers who had immigrated to the United States. DESIGN:
      Japanese and South American immigrant mothers of 2-year-olds completed a
      standardized survey of parenting knowledge and provided information about
      sociodemographic and infant health status. Their data were compared with European
      American mothers in the United States. RESULTS: Immigrant mothers scored
      approximately 70% on the evaluation of parenting knowledge, significantly lower
      than multigenerational US mothers. The majority of immigrant mothers did not know
      correct answers for 25% of the items, and their incorrect answers were mostly to
      questions about normative child development. CONCLUSIONS: Parents' knowledge is
      relevant to pediatricians' evaluations of the health and welfare of children as
      understood by their parents. Gaps in parenting knowledge have implications for
      clinical interactions with parents, child diagnosis, pediatric training, and
      parent education.

PMID- 15520090
TI  - Inequality of access to surgical specialty health care: why children with
      government-funded insurance have less access than those with private insurance in
      Southern California.
AB  - OBJECTIVE: More than 25 million children in the United States are dependent on
      federal and state medical insurance programs for their health care needs. In
      California, 3.25 million children depend on Medi-Cal for their health insurance.
      In Southern California alone, the figure is as high as 1.81 million. However,
      9.30 million children nationally and 1.55 million in California have no health
      insurance. Various public policies that would increase enrollment in these
      programs are being discussed to address this problem. However, before their
      implementation, it is important to understand what impact such policies would
      have on the actual delivery of health care to this patient population. In
      California, 2 predominant health care delivery models exist for Medi-Cal: a fee
      for-service (so-called regular or straight Medi-Cal) and a managed care plan. One
      third of the children in Medi-Cal in the state are enrolled in the fee-for
      service plan with the remainder in the managed care plan, whereas in Southern
      California, this figure is slightly lower at 28% in the fee-for-service plan. The
      objective of this study was to determine the number of otolaryngologists in
      Southern California who would offer a new patient appointment for an evaluation
      for tonsillectomy for a child with commercial insurance versus government-funded
      (Medi-Cal) insurance through direct contact with the physician and to determine
      whether the surgeon would offer to perform the procedure or refer the patient to
      another institution and to identify the specific reason(s) for any disparity in
      access to health care. METHODS: A written questionnaire was sent via regular mail
      to 303 otolaryngologists in the Southern California area in 2003. RESULTS: A
      total of 100 fully completed questionnaires were received. Ninety-seven surgeons
      would offer an office appointment to a child with commercial insurance as
      compared with only 27 for a child with Medi-Cal. Of those 27 surgeons, 8 would
      then refer the child to another physician to perform the surgery, and only 19
      would actually offer to perform surgery, if indicated. Reasons provided for not
      offering an office appointment or surgery for the child with Medi-Cal include
      excessive paperwork and/or administrative burdens (96%), low monetary
      reimbursement for the surgery (92%), and low monetary reimbursement for the
      office visit (87%). CONCLUSIONS: There is a tremendous inequality of access to
      surgical specialty health care for children with government-funded insurance when
      compared with those with commercial insurance in Southern California. Physicians
      indicate that this disparity is related to excessive administrative burdens and
      low monetary reimbursement. The implications of our findings on public health
      care policies are discussed.

PMID- 15520091
TI  - Integrating adherence to highly active antiretroviral therapy into children's
      daily lives: a qualitative study.
AB  - OBJECTIVE: To acquire a deeper understanding of factors that influence adherence
      to highly active antiretroviral therapy (HAART) in a pediatric population.
      METHODS: We performed a qualitative study of adherence in children who receive
      HAART in a Belgian pediatric acquired immune deficiency syndrome referral center.
      Eleven primary caregivers were interviewed to assess their child's adherence and
      influencing factors. The interview guidelines were developed on the basis of an
      extensive literature review. Adherence to treatment was assessed using
      caregivers' self-report and laboratory results. Content analysis for common items
      was performed, and statements of adherent and less-adherent patients were
      compared. RESULTS: Three main factors influenced adherence. Adherent patients
      were found to internalize the medical information to a stronger extent than less
      adherent patients. Adherent patients showed stronger motivation to stick to the
      medical regimen on the basis of personal cost-benefit analyses, ie, perceived
      benefits outweighed the costs or difficulties experienced. Adherent patients
      developed greater problem-solving capacities, ie, ways to deal with practical
      complications of medication intake. The interviews revealed a fourth, more
      dynamic component: knowledge, motivation, and capacities evolved in a progressive
      way, related to individual stages of coping with human immunodeficiency virus
      (HIV). CONCLUSIONS: The data suggest that coping with HIV and the process of
      establishing good adherence may be interrelated. Caregivers who accept the
      disease may be more likely to internalize the received information and thus
      develop a stronger motivation to fight for the child's life. Problem-solving
      skills sustain this adherence, and medication becomes a priority in the adherent
      caregivers' daily lives. On the contrary, less-adherent caregivers may be
      situated at less advanced stages of the coping process. Thus, tailor-made
      approaches adapted to the individual HIV-related coping strategies need to be
      developed to improve adherence in children and caregivers.

PMID- 15520092
TI  - Policy versus practice: comparison of prescribing therapy and durable medical
      equipment in medical and educational settings.
AB  - OBJECTIVE: The American Academy of Pediatrics (AAP) has promoted pediatrician
      involvement in the care of children with special health care needs (CSHCN),
      including the prescription and/or supervision of therapies and durable medical
      equipment (DME) for children in both medical and educational settings, such as
      schools and early intervention programs. Through this survey, we attempted to
      quantify objectively how pediatricians direct and coordinate therapy and DME for
      CSHCN and how these efforts correlate with AAP recommendations. METHODS: A survey
      was mailed to a random sample of 500 physicians listed in the AAP directory,
      resulting in a final sample of 217 responding physicians who indicated that they
      provide services to CSHCN. Results of the survey were reported as proportions,
      means with standard deviations, or medians with interquartile range. Comparisons
      of proportions among certain subgroups of interest were made using Fisher exact
      tests. RESULTS: The most recent AAP policy revision addressing the role of
      physicians in prescribing therapy services for children with motor disabilities
      appeared in Pediatrics 1996. It listed 6 key items that should be part of a
      therapy prescription: diagnosis, precautions, type, frequency, anticipated goals
      (educators may prefer the term "objectives"), and duration. The policy addressed
      and emphasized the need for what may be additional objectives, namely regular
      communication between all parties involved, ongoing supervision and reevaluation
      of the program and problem, and awareness of other community resources for
      possible referrals. Except for providing a diagnosis, the majority of surveyed
      pediatricians do not regularly comply with AAP policy recommendations on
      prescribing therapies and DME in medical and educational settings. Physicians who
      were trained before 1980 tend to follow AAP recommendations more closely than
      later graduates. Decreasing involvement of private outpatient pediatricians in
      coordinating and supervising CSHCN's care was noted. Furthermore, the majority is
      willing to defer decisions about treatment and goals to nonphysician health care
      providers (NPHCPs) and, in some cases, even equipment vendors. More than two
      thirds of the respondents indicated that they would sign a prescription for
      therapy without their previous initiation if it had been initiated by a
      therapist. Likewise, most respondents said that they would sign a wheelchair
      prescription sent to them by a therapist. Few expressed confidence in determining
      the appropriateness of leg brace (orthosis) prescriptions and arm/hand brace
      prescriptions. The majority of survey participants said that they give open-ended
      length of time (no limits under 1 year) on prescriptions for therapy services as
      part of school-based programs. However, patients' conditions and their
      therapeutic or equipment needs may change during the school year. Because open
      ended prescriptions do not require periodic renewal, they do not provide
      opportunities for periodic feedback that helps to ensure that the pediatrician is
      kept abreast of the patient's status and progress. The majority of respondents
      indicated that they would see a patient before signing either a therapy or DME
      prescription if they had not seen that patient in the past year. A little more
      than half of survey respondents said that they would participate initially in
      recommending which professional services or therapies should be performed as part
      of early intervention programs most of the time, but one third said that they
      participated less than half the time and approximately 14% said that they never
      participated. A majority would require being involved before authorizing therapy
      services as part of a school-based program, but a substantial minority would
      provide retroactive authorization for services that they did not initiate
      themselves. More than three quarters of respondents would prefer to let the
      therapist or educator set the goals. Only 58% of pediatricians reported receiving
      a detailed progress report once or twice a year, and approximately one fifth
      received no reports on patients in school-based programs. A literature review
      suggested that there are different perceptions among physicians and educationally
      based service providers regarding the physician's role in initiating and
      supervising educationally based services and equipment, which may influence the
      extent of physician involvement. AAP and other professional organizations, such
      as the American Medical Association and the American Academy of Physical Medicine
      and Rehabilitation, as well as federal guidelines and third-party payers
      emphasize the important role of physicians in initiating, determining the medical
      necessity, and ordering of services as well as in ongoing patient treatment. If
      therapists through their states' scope of practice guidelines have autonomy of
      practice or if the school self-funds educationally based services, then there may
      be no issues regarding physician authorization. However, if a physician's
      authorization is required for reimbursement, then the physician's professional,
      legal, and practice guidelines come into play. Physicians should be conscientious
      about fulfilling their responsibilities in serving as the medical home and
      supervising and monitoring medical services for their patients in both community
      and educational settings. Failure to properly fulfill the responsibilities
      inherent in signing a prescription may bring adverse consequences for the patient
      as well subject the physician to legal liability if adverse events occur.
      CONCLUSIONS: Ideally, there should be a seamless continuity and cooperation among
      the environments of medicine, home, community, and education rather than separate
      and perhaps conflicting domains. All health care professionals and other service
      providers involved should be acknowledged as collaborative team members. Except
      for provision of the diagnosis, the majority of surveyed pediatricians do not
      comply with AAP policy recommendations on prescribing community/medical-based and
      educationally based services for CSHCN. Furthermore, the majority are willing to
      defer these decisions to other NPHCP. This raises issues regarding overall
      continuity of care versus care of the child in a variety of environments, the
      concept of the medical home, and legal risk as a result of failure to follow
      federal and state practice guidelines. Also, there seem to be different cultural
      perceptions among physicians and educationally based service providers regarding
      the physician's role in educationally based services. These cultural differences
      should be explored further to promote a greater collegial cooperation and
      understanding. Decreasing involvement of private outpatient pediatricians in
      coordinating and supervising CSHCN care and a trend toward greater deference to
      NPHCP since 1979 were noted. If the numerous policies and guidelines previously
      promoted by AAP have not had a significant impact on pediatrician practices in
      these fields, then other, more effective alternatives should be explored.

PMID- 15520093
TI  - Neurologic complications associated with influenza A in children during the 2003
      2004 influenza season in Houston, Texas.
AB  - OBJECTIVES: Our objectives were to (1) describe the clinical characteristics of
      and viruses isolated from patients who presented with neurologic symptoms
      associated with influenza A infection and were hospitalized at Texas Children's
      Hospital during October and November 2003 and (2) to raise awareness of the
      neurologic complications of influenza among US children. METHODS: We reviewed the
      medical and laboratory records of all children who were hospitalized with
      neurologic symptoms and who also had evidence of influenza virus infection by
      rapid antigen testing or viral isolation. RESULTS: Eight children aged 5 months
      to 9 years with neurologic complications associated with influenza A were
      identified. None of the children had received the influenza vaccine. Four
      presented with seizures, 3 with mental status changes, and 1 with mutism. All but
      1 of the patients had influenza A viral antigen detected in nasal wash samples.
      Influenza A virus was isolated in culture from nasal wash specimens obtained from
      6 of the patients; influenza A virus was also isolated from the cerebrospinal
      fluid of 1 of these patients. None of the patients had serum metabolic
      abnormalities or other cerebrospinal fluid abnormalities. Three of the patients
      had brain imaging abnormalities. Five of the patients were treated with
      antivirals. All 8 of the patients survived, 6 with complete recovery and 2 with
      sequelae (1 mild and 1 severe). CONCLUSIONS: Neurologic symptoms and sequelae
      were associated with influenza A virus infection in children during the 2003-2004
      influenza season in Houston, Texas. Influenza should be considered in the
      differential diagnosis in patients with seizures and mental status changes,
      especially if they present with respiratory symptoms or during an influenza
      outbreak.

PMID- 15520094
TI  - Dental screening and referral of young children by pediatric primary care
      providers.
AB  - OBJECTIVE: Several health care organizations recommend that physicians provide
      preventive dentistry services, including dental screening and referral. This
      study is the first to investigate characteristics of medical providers that
      influence their referral to a dentist of children who are at risk for dental
      disease. METHODS: A cross-sectional survey was undertaken of primary care
      clinicians in 69 pediatric practices and 49 family medicine practices who were
      enrolled in a study to evaluate a pediatric preventive dentistry program targeted
      toward Medicaid-eligible children in North Carolina. A 100-item, self
      administered questionnaire with 23 items on some aspect of dental referral
      elicited providers' knowledge and opinions toward oral health, their provision of
      dental services, and their confidence in providing these services. We
      hypothesized that providers' dental knowledge, opinions about the importance of
      oral health, and confidence in providing oral health services would be associated
      with their propensity to refer children who are younger than 3 years and are
      suspected of having risk factors for future dental disease or a few teeth in the
      beginning stages of decay. We also hypothesized that providers' perceived
      referral difficulty would affect their referral activities. Patient
      characteristics (tooth decay status, insurance status, immigrant status, English
      speaking), practice characteristics (setting, number of providers, patient
      volume, busyness), practice environment (perceived and actual availability of
      dentists), and other provider characteristics (gender, type, practice experience,
      board certification, training in oral health during or after professional
      education, hours worked, teaching of residents, preventive behaviors) were
      assessed and used as control variables. Preliminary bivariate analysis (analysis
      of variance, chi2) identified characteristics associated with referral activity.
      Multivariable logistic regression analysis using backward stepwise logistic
      regression tested the posed hypotheses, with provider, practice, and patient
      characteristics included as potential control variables. RESULTS: Nearly 78% of
      169 primary care clinicians who participated in the survey reported that they
      were likely to refer children who had signs of early decay or high risk for
      future disease. Approximately half (54%) call a dental office sometimes or more
      frequently to make an appointment for a child whom they refer, but the most
      common method is to give the caregiver the name of a dentist without additional
      assistance (96%). Bivariate analysis revealed that providers who had high
      confidence in their ability to perform screenings and reported low overall
      referral difficulty were more likely to refer children. Bivariate analyses also
      found that providers who were not in group practices, were board certified,
      graduated 20 years ago or more, saw 80 or more patients per week, had >60% of
      their total patients who were infants and toddlers, and saw >3.5 patients per
      hour were significantly less likely to refer at-risk children for dental care. No
      patient characteristics were associated with referral. The regression model
      revealed that an increase in odds of referral was significantly associated with
      confidence in screening abilities (odds ratio [OR]: 5.0; 95% confidence interval
      [CI]: 1.7-15.1), low referral difficulty (OR: 6.0; 95% CI: 1.0-34.5), and group
      practice (OR: 4.2; 95% CI: 1.4-12.1). Having a patient population of >60% infants
      or toddlers was significantly associated with a decrease in odds of referral (OR:
      0.2; 95% CI: 0.1-0.7). Oral health knowledge and opinions did not help to explain
      referral practices. CONCLUSIONS: Tooth decay remains a substantial problem in
      young children and is made worse by existing barriers that prevent them from
      obtaining dental care. Because most children are exposed to medical care but not
      dental care at an early age, primary care medical providers have the opportunity
      to play an important role in helping children and their families gain access to
      dental care. This study has identified several factors that need consideration in
      the further exploration and development of primary care physicians' role in
      providing for the oral health of their young patients. First, instructional
      efforts to increase providers' dental knowledge or opinions of the importance of
      oral diseases are unlikely to be effective in increasing dental referral unless
      they include methods to increase confidence in providers' ability to identify and
      appropriately refer children with disease. Medical education in oral health may
      need to be designed to include components that address self-efficacy in providing
      risk assessment, early detection, and referral services. Traditional, didactic
      instruction does not fulfill these requirements, but because the effectiveness of
      instructional methods for teaching medical providers oral health care,
      particularly confidence-building aspects, is untested, controlled evaluations are
      necessary. A second conclusion from this study is that the referral environment
      is more important than provider knowledge, experience, opinions, or patient
      characteristics in determining whether medical practitioners refer at-risk
      children for dental care. Most providers in this study held positive opinions
      about providing dental services in their practices, had relatively high levels of
      knowledge, screened for dental disease, accessed risk factors in their patients,
      and referred; they can be instrumental in helping young children get dental care,
      yet most providers face difficulties in making dental referrals, and changes in
      the availability of dental care will be necessary to decrease these barriers
      before referral can be most effective. The longer-term approach of increasing the
      number of dental graduates can be complemented in the shorter term by other
      approaches to increase dentists' participation in Medicaid, such as increases in
      reimbursement rates; training general dentists to treat young children; and
      community organization activities to link families, physicians, dentists, and
      public programs such as Early Head Start. Finally, pediatric primary health care
      providers can provide oral health promotion and disease prevention activities,
      thereby eliminating or delaying dental disease and the need for treatment at a
      very young age. However, effective and appropriate involvement of pediatric
      primary care clinicians can be expected only after they receive the appropriate
      training and encouragement and problems with the dental referral environment are
      addressed.

PMID- 15520095
TI  - A new complication of stem cell transplantation: measles inclusion body
      encephalitis.
AB  - Measles inclusion body encephalitis (MIBE) is a disease of the immunocompromised
      host and typically occurs within 1 year of acute measles infection or
      vaccination. We report a 13-year-old boy who had chronic granulomatous disease
      and presented 38 days after stem cell transplantation with afebrile focal
      seizures that progressed despite multiple anticonvulsants. After an extensive
      diagnostic evaluation, brain biopsy was performed, revealing numerous
      intranuclear inclusion bodies consistent with paramyxovirus nucleocapsids.
      Measles studies including reverse transcriptase-polymerase chain reaction and
      viral growth confirmed measles virus, genotype D3. Immunohistochemistry was
      positive for measles nucleoprotein. Despite intravenous ribavirin therapy, the
      patient died. MIBE has not been described in stem cell recipients but is a
      disease of immunocompromised hosts and typically occurs within 1 year of measles
      infection, exposure, or vaccination. Our case is unusual as neither the patient
      nor the stem cell donor had apparent recent measles exposure or vaccination, and
      neither had recent travel to measles-endemic regions. The patient had an
      erythematous rash several weeks before the neurologic symptoms; however, skin
      biopsy was consistent with graft-versus-host disease, and immunohistochemistry
      studies for measles nucleoprotein were negative. As measles genotype D3 has not
      been seen in areas where the child lived since his early childhood, the
      possibility of an unusually long latency period between initial measles infection
      and MIBE is raised. In addition, this case demonstrates the utility of brain
      biopsy in the diagnosis of encephalitis of unknown cause in the immunocompromised
      host.

PMID- 15520096
TI  - Essential tremor among children.
AB  - OBJECTIVE: To characterize the clinical and therapeutic aspects of essential
      tremor (ET) among children. BACKGROUND: ET, an autosomal dominant disorder, has
      been studied extensively among adults, but little is known regarding its
      occurrence, clinical characteristics, treatment, and prognosis in pediatric
      populations. Often stigmatized as a disorder of the elderly, ET may be
      misdiagnosed among children. Previous studies of childhood-onset ET were limited
      by small sample sizes. METHODS: Clinical data, including gender, age at onset,
      family history, associated disorders, and response to treatment, were collected
      for consecutive patients diagnosed with childhood-onset ET at the Movement
      Disorders Clinic at Baylor College of Medicine. RESULTS: Of the 39 patients with
      ET, 29 (74.4%) were male. The mean age at onset was 8.8 +/- 5.0 years, and the
      mean age at evaluation was 20.3 +/- 14.4 years. A family history of tremor was
      noted for 79.5% of the patients. Eighteen (46.2%) had some neurologic
      comorbidity, such as dystonia, which was noted for 11 patients (28.2%). Only 24
      of the patients (61.5%) were treated with a specific antitremor medication; 5 of
      the 12 patients treated with propranolol experienced improvement. CONCLUSIONS:
      Concomitant movement disorders, such as dystonia, are common among patients with
      childhood-onset ET, which supports the concept that ET is a heterogeneous
      disorder. Treatment strategies used for adult patients with ET seem to be
      effective also for children with ET, although controlled therapeutic trials in
      this population of patients with ET are lacking.

PMID- 15520097
TI  - Increased use of second-generation macrolide antibiotics for children in nine
      health plans in the United States.
AB  - BACKGROUND: Widespread use of broad-spectrum antibiotics contributes to
      increasing rates of bacterial resistance to antibiotics. Second-generation
      macrolides have become popular for use among children because of their broad
      spectrum and favorable dosing and side-effect profiles, although experts do not
      generally recommend them for use as initial treatment of infections among younger
      children. OBJECTIVE: To assess trends in second-generation macrolide use from
      1996 to 2000 among children treated as outpatients in 9 US health plans,
      including associated diagnoses and use as initial treatment. METHODS: We sampled
      claims data for 25000 children, 3 months to <18 years of age, who were enrolled
      between September 1, 1995, and August 31, 2000, in each of 9 US health plans.
      Medications dispensed were linked with ambulatory visit claims to assign
      diagnoses. Dispensings without another antibiotic dispensing recorded in the
      previous 42 days were analyzed as initial treatment of a new illness episode. We
      analyzed trends in prescribing overall, for initial therapy, and, within specific
      diagnoses, for differences among health plans. RESULTS: From 1995-1996 to 1999
      2000, although overall antibiotic use decreased from 1.15 to 0.91 dispensings per
      person-year, second-generation macrolide use increased from 0.022 to 0.063
      dispensings per person-year. Use as a proportion of all antibiotic dispensings
      increased from 1.9% to 6.9%, and use as initial therapy increased from 1.4% to
      6%. For children <6 years of age, second-generation macrolide use as initial
      therapy increased from 0.9% to 5.0% for otitis media and from 5.2% to 24.0% for
      pneumonia. There was a wide range of prescribing rates among health plans during
      the last year of the study, from 0.006 to 0.135 dispensings per person-year.
      CONCLUSIONS: Despite recent trends toward decreased antibiotic use among
      children, the use of second-generation macrolides among children has increased
      dramatically, even among younger children, for whom use for initial treatment of
      illness is not recommended. Large differences in prescribing rates exist among
      health plans. Continued efforts to promote the use of narrower-spectrum agents
      when appropriate are needed.

PMID- 15520098
TI  - Group A streptococci among school-aged children: clinical characteristics and the
      carrier state.
AB  - OBJECTIVE: A 4-year longitudinal study of school-aged children was conducted to
      describe the clinical characteristics and epidemiologic features of infections
      with group A streptococci (GAS). METHODS: Between 1998 and 2002, surveillance
      throat cultures were performed twice per month (October to May) for a cohort of
      elementary school children in Pittsburgh, Pennsylvania. In addition, throat
      cultures were obtained during any respiratory illness. Erythromycin and
      clindamycin susceptibility testing was performed for all isolates. Molecular
      typing was performed with field-inversion gel electrophoresis. Representative
      isolates from each field-inversion gel electrophoresis group were emm typed.
      Strict definitions were used to characterize each GAS infection. Children were
      classified into 4 categories each year, ie, single episode, recurrent episodes,
      carriers of GAS, and no infections. RESULTS: A total of 48 to 100 children per
      year were studied for 4 years; 61 (49%) were male. The mean age was 9.6 years
      (range: 5-15 years). A total of 5658 throat cultures were performed; 878 (15.5%)
      were positive for GAS. Antimicrobial agents were used to treat 209 episodes of
      infection. Thirteen emm types were observed during the 4-year period. GAS were
      isolated most often from children who were carriers; isolates from single
      episodes were next most common. Children carried a single emm type for a mean of
      10.8 weeks (range: 3-34 weeks). Carriers were likely to be classified again as
      carriers in subsequent years and frequently switched emm types. Sixty-two percent
      of the children had > or =1 year with no infections. CONCLUSIONS: GAS infections
      are common among school-aged children. The majority of positive throat cultures
      observed in this longitudinal study were obtained from children who were carriers
      of GAS. Carriers switched emm types but tended to become carriers repeatedly
      during the study. Practitioners should consider treating children known to be GAS
      carriers when they develop a new illness that is consistent with streptococcal
      pharyngitis, because they may acquire new emm types and be at risk for rheumatic
      heart disease.

PMID- 15520099
TI  - Children with unexplained chronic pain: do pediatricians agree regarding the
      diagnostic approach and presumed primary cause?
AB  - OBJECTIVE: To investigate the opinions of general pediatricians regarding
      children with unexplained chronic pain (UCP), with respect to the presumed cause
      of the pain and the optimal diagnostic approach for these children. DESIGN:
      Diagnostic follow-up study. SETTING: Outpatient clinic of a university children's
      hospital. PARTICIPANTS: A total of 134 consecutive patients, 8 to 18 years of
      age, referred for pain of > or =3-month duration without a satisfactory
      explanation at presentation. METHODS: A full copy of the patient records from
      routine medical practice and data from standardized psychiatric assessments,
      standardized questionnaires, and standardized follow-up assessments were provided
      to 17 pediatricians assigned to 3 panels. MAIN OUTCOME MEASURES: Agreement
      regarding the presumed primary cause and diagnostic approach for children with
      UCP, with consensus being defined as > or =80% agreement among the pediatricians.
      RESULTS: The mean age of the children (73% girls) was 11.8 years (SD: 2.6 years).
      Psychiatric (co)morbidity was present for 60% of the children. Consensus
      regarding the presumed primary cause was reached for 43% of the patients (58 of
      134 patients), ie, 72% (42 of 58 patients) primarily dysfunctional, 17% (10 of 58
      patients) primarily psychologic, and 10% (6 of 58 patients) primarily somatic.
      Consensus regarding the diagnostic approach was reached for 63% of the children
      (84 of 134 children), leaving more than one-third of the children (37%) without
      diagnostic consensus. CONCLUSIONS: The relatively high rates of disagreement
      regarding the optimal diagnostic approach and presumed primary cause illustrate
      the difficulties of diagnostic evaluation and subsequent therapeutic strategy
      design for this patient group. Therefore, children with UCP might be at risk for
      suboptimal care.

PMID- 15520100
TI  - Usefulness of the serum electrolyte panel in the management of pediatric
      dehydration treated with intravenously administered fluids.
AB  - BACKGROUND: The serum electrolyte panel (SEP) is a frequently ordered laboratory
      test, but it has unproven usefulness in the treatment of dehydrated pediatric
      patients. Our study purpose was to evaluate the usefulness of routinely ordering
      a SEP in the treatment of dehydrated pediatric patients receiving intravenous
      fluids (IVFs). METHODS: Children 2 months to 9 years of age who were receiving
      IVFs because of dehydration were prospectively studied in a pediatric emergency
      department (PED). Historical data, physical examination findings, degree of
      dehydration, and SEP results were recorded. After patient evaluation, attending
      physicians documented whether they would have ordered a SEP. Outcome measurements
      included changes in clinical management on the basis of SEP results, as well as
      correlations of dispositions and unscheduled return visits (URVs) with SEP
      results. RESULTS: A total of 182 patients were enrolled in the study. One hundred
      eleven patients had mild dehydration, 55 moderate dehydration, and 16 severe
      dehydration. Eighty-eight patients (48%; 95% confidence interval: 41-56%) had >
      or =1 abnormal SEP value. Clinically relevant findings included bicarbonate
      levels of <16 mmol/L for 28% of patients, hypoglycemia for 9.9%, hypokalemia for
      6.0%, and hypernatremia for 3.0%. The attending physicians predicted that a SEP
      would be clinically important for 34% of all patients. There was a 58%
      sensitivity in detecting which children would have clinically significant SEP
      results. Overall, SEP results changed clinical management in 10.4% of cases. One
      hundred sixty-five (91%) of the patients were discharged from the PED (including
      48 who were initially observed), of whom 7 (3.8%) had URVs to the PED within 72
      hours and were given additional IVFs. Seventeen patients were admitted (median:
      2.6 days), 2 of whom had URVs after hospital discharge for additional IVFs.
      CONCLUSIONS: On the basis of initial presentation, attending physicians were poor
      at predicting which children would have clinically significant SEP results. Low
      bicarbonate values were correlated with observation unit use but not with
      hospitalization or URVs. The observation unit provided effective care for a
      subset of dehydrated patients, avoiding the need for hospitalization. Obtaining a
      SEP can provide useful information for the treatment of some children receiving
      IVFs because of dehydration.

PMID- 15520101
TI  - Well-child visits in the video age: pediatricians and the American Academy of
      Pediatrics' guidelines for children's media use.
AB  - OBJECTIVES: The goal of this study was to evaluate awareness of, agreement with,
      and implementation of the American Academy of Pediatrics (AAP) media use
      guidelines among pediatricians. Pediatricians' beliefs about several media
      effects were also measured, as was their own media use. Pediatricians were also
      asked about how often they make media recommendations as part of anticipatory
      guidance during well-child visits, as well as the perceived efficacy of and
      barriers to making such recommendations. DESIGN: A cross-sectional survey mailed
      to all members of the Minnesota chapter of the AAP. PARTICIPANTS: A total of 365
      pediatricians completed the survey. MEASURES: The 58-item survey assessed
      familiarity with, agreement with, and implementation of each of 3 AAP
      recommendations, to limit children's media time, to discourage television (TV)
      viewing among children <2 years of age, and to encourage alternative
      entertainment for children. Pediatricians were also asked about the perceived
      effectiveness of and barriers to guideline implementation. In addition,
      pediatricians were asked to report their own TV viewing habits and their opinions
      about how much media affect children's health and behavior. RESULTS: Most
      pediatricians were familiar with and also agreed with the 3 AAP recommendations.
      Their agreement may stem from the fact that pediatricians almost universally
      believe that children's media use negatively affects children in many different
      areas, including children's aggressive behavior, eating habits, physical activity
      levels, risk for obesity, high-risk behaviors, and school performance.
      Pediatricians were most likely to have encouraged alternative entertainment and
      were least likely to have discouraged TV viewing for children <2 years of age.
      The majority of pediatricians provided all 3 recommendations to parents at least
      sometimes. Most pediatricians reported that their recommendations were at least a
      little effective when they did make them. The most frequent barrier pediatricians
      reported facing was a lack of parental motivation or support for the
      recommendations, with approximately one-third of pediatricians also citing a lack
      of time and a sense of futility in affecting patients' media habits as barriers.
      Finally, pediatricians who watched the greatest amounts of TV were significantly
      more likely than those who watched less to think that the AAP recommendation to
      limit children's total media time to no more than 1 to 2 hours per day is
      unrealistic, whereas those who watched less were more likely to agree with the
      recommendation. CONCLUSIONS: Results suggest that the efforts of the AAP in
      reaching pediatricians have been largely successful, with the majority of
      pediatricians in Minnesota being aware of and agreeing with the 3 major
      recommendations suggested by the AAP policy statement on children, adolescents,
      and television. However, implementation of the recommendations could be improved,
      especially because pediatricians usually think that the recommendations are at
      least a little effective when made. Strategies for overcoming barriers to making
      recommendations need to be addressed, including the sense of futility in
      affecting media use that some pediatricians may feel.

PMID- 15520102
TI  - A double-blind, randomized, placebo-controlled trial of acupuncture for the
      treatment of childhood persistent allergic rhinitis.
AB  - OBJECTIVE: To compare active acupuncture with sham acupuncture for the treatment
      of persistent allergic rhinitis among children. METHODS: Subjects with persistent
      allergic rhinitis were recruited from the pediatric outpatient clinic. They were
      randomized to receive either active acupuncture or sham acupuncture. Main outcome
      measures included daily rhinitis scores, symptom-free days, visual analog scale
      scores for immediate effects of acupuncture, daily relief medication scores,
      blood eosinophil counts, serum IgE levels, nasal eosinophil counts, patients' and
      parents' preferences for treatment modalities, and adverse effects. RESULTS:
      Eighty-five patients were recruited from the pediatric outpatient clinic at Kwong
      Wah Hospital, in Hong Kong. Thirteen patients withdrew before randomization; 35
      patients (mean age: 11.7 +/- 3.2 years) were randomized to receive active
      acupuncture for 8 weeks, and 37 patients (mean age: 11 +/- 3.8 years) were
      randomized to receive sham acupuncture for 8 weeks. Acupuncture was performed
      twice per week for both groups. Both the assessing pediatricians and the patients
      were blinded. There were significantly lower daily rhinitis scores and more
      symptom-free days for the group receiving active acupuncture, during both the
      treatment and follow-up periods. The visual analog scale scores for immediate
      improvement after acupuncture were also significantly better for the active
      acupuncture group. There was no significant difference in the following outcome
      measures between the active and sham acupuncture groups: daily relief medication
      scores, blood eosinophil counts, serum IgE levels, and nasal eosinophil counts,
      except for the IgE levels before and 2 months after acupuncture in the sham
      acupuncture group. No severe adverse effects were encountered. Numbness,
      headache, and dizziness were found in both the active and sham acupuncture
      groups, with no difference in incidence, and the effects were self-limiting.
      CONCLUSIONS: This study showed that active acupuncture was more effective than
      sham acupuncture in decreasing the symptom scores for persistent allergic
      rhinitis and increasing the symptom-free days. No serious adverse effect was
      identified. A large-scale study is required to confirm the safety of acupuncture
      for children.

PMID- 15520103
TI  - Hospital staff and family perspectives regarding quality of pediatric palliative
      care.
AB  - BACKGROUND: Development of a pediatric palliative care program was preceded by a
      needs assessment that included a staff survey and family interviews regarding
      improving pediatric palliative care. METHODS: Four hundred forty-six staff
      members and community physicians responded to a written survey regarding comfort
      and expertise in delivering end of life care. Sixty-eight family members of 44
      deceased children were interviewed regarding treatment, transition to palliative
      care, and bereavement follow-up contact. Frequencies were generated for responses
      to the staff survey. Five interviewers reviewed the families' narratives and
      identified frequently occurring themes. RESULTS: Staff members reported feeling
      inexperienced in communicating with patients and families about end of life
      issues, transition to palliative care, and do not resuscitate status. Families
      reported distress caused by uncaring delivery of bad news and careless remarks
      made by staff members. Staff members reported feeling inexperienced in symptom
      and pain management and described occasions when pain could have been better
      managed. Families believed pain had been managed as well as possible despite
      observing their children suffer. Fifty-four percent of staff members reported
      that adequate support was not provided for those who treat dying children. Staff
      members and family members stated their desire for more support. Staff members
      who described their most difficult experiences caring for a dying child
      referenced personal pain and inadequate support most frequently. CONCLUSIONS:
      Albeit from different perspectives, staff members and family members shared
      common concerns and experiences regarding pediatric palliative care. These
      experiences emphasize the need for additional systematic study, improved
      education and support for staff members, and continued development of more
      effective and compassionate delivery of pediatric palliative care.

PMID- 15520104
TI  - Screening for domestic violence in a general pediatric clinic: be prepared!
AB  - OBJECTIVES: Exposure to violence, particularly domestic violence (DV), negatively
      affects children's physical, emotional, and cognitive well-being. The American
      Academy of Pediatrics recommends routine DV screening of female caretakers of
      pediatric patients. Few reports of screening in pediatric practices exist, and
      none have reported outcomes from a resident-run urban academic center. We set out
      to determine whether the use of the Partner Violence Screen (PVS) increases
      detection of DV and to test the mechanics of implementing large-scale DV
      screening in a busy, pediatric residency training clinic. METHODS: Using the PVS,
      we screened a sample of consecutive female caretakers/guardians of children seen
      for pediatric care in the general pediatric clinic of Children's Hospital of
      Michigan from March 1, 2002, through February 28, 2003. Positive screens obtained
      during the study period were compared with the number of DV referrals received by
      the clinic social workers from January 1, 2001, through December 31, 2001, before
      PVS screening began. To test the mechanics of screening, we also analyzed the
      number of forms returned blank or marked "no opportunity to screen" in the last 8
      months of the study period. RESULTS: In the 12 months before use of the PVS, our
      social work department received 9 referrals because of DV from the general
      pediatric clinic, among a total of 5446 caretakers/guardians bringing 6380
      children for a total of 13,576 patient care visits. In contrast, the social work
      department received 164 referrals because of positive screening results among
      5445 caretakers/guardians bringing 7429 children for 17,346 patient care visits
      in the 12-month study period after introduction of the PVS. Fourteen of 164
      positive PVSs were found to involve nondomestic violence perpetrated by
      nonpartners or violence with the patient as the victim, not the mother or female
      caretaker. A total of 150 PVSs involved true DV. The difference in identification
      of DV with the PVS, compared with the rate before its introduction, was highly
      significant. The positive predictive value for the PVS was 91.5%, and the
      identified prevalence rate was 3.7%. In the last 8 months of the study period,
      6301 of 8055 PVS forms (78%) were completed; 1754 of 8055 PVS forms (22%) were
      left blank, but it was not possible to determine whether these represented
      duplicate screening forms for instances in which the mother or female caretaker
      had brought >1 child for care. CONCLUSIONS: Formal screening for DV with the PVS
      in this study setting of a busy, urban, academic, general pediatric clinic
      appeared to be very successful, in terms of increasing referrals and
      documentation of previously unrecognized DV situations. This increase signals the
      need for resources (time and/or social work services) to provide appropriate
      referral services. The PVS identifies nonpartner violence occasionally.

PMID- 15520105
TI  - Physical activity among children attending preschools.
AB  - OBJECTIVES: Obesity rates are increasing among children of all ages, and reduced
      physical activity is a likely contributor to this trend. Little is known about
      the physical activity behavior of preschool-aged children or about the influence
      of preschool attendance on physical activity. The purpose of this study was to
      describe the physical activity levels of children while they attend preschools,
      to identify the demographic factors that might be associated with physical
      activity among those children, and to determine the extent to which children's
      physical activity varies among preschools. METHODS: A total of 281 children from
      9 preschools wore an Actigraph (Fort Walton Beach, FL) accelerometer for an
      average of 4.4 hours per day for an average of 6.6 days. Each child's height and
      weight were measured, and parents of participating children provided demographic
      and education data. RESULTS: The preschool that a child attended was a
      significant predictor of vigorous physical activity (VPA) and moderate-to
      vigorous physical activity (MVPA). Boys participated in significantly more MVPA
      and VPA than did girls, and black children participated in more VPA than did
      white children. Age was not a significant predictor of MVPA or VPA. CONCLUSIONS:
      Children's physical activity levels were highly variable among preschools, which
      suggests that preschool policies and practices have an important influence on the
      overall activity levels of the children the preschools serve.

PMID- 15520106
TI  - Prognosis for ambulation in cerebral palsy: a population-based study.
AB  - OBJECTIVES: To determine independent predictors of ambulation among children with
      cerebral palsy and to develop a simple tool that estimates the probability that a
      child will walk. METHODS: In a retrospective study of all children with cerebral
      palsy who were not yet walking at 2 to 3(1/2) years of age, while receiving
      services from the California Department of Developmental Services during the
      years 1987-1999, we analyzed medical and functional data obtained annually by
      Department of Developmental Services physicians and social workers. Using
      logistic regression analyses, we determined independent predictors of a child's
      ability to walk well alone at least 20 feet, without assistive devices, by age 6.
      We then estimated the probabilities of walking at various levels of ability over
      time, using multistate survival analysis. RESULTS: Of 5366 study subjects, 2295
      (43%) were evaluated at age 6; 12.8% could walk independently and 18.4% walked
      with support. Independent predictors of successful ambulation included early
      motor milestones such as sitting (odds ratio: 12.5; 95% confidence interval: 5.8
      27.2) and pulling to a stand (odds ratio: 28.5; 95% confidence interval: 13.4
      60.4) when compared with lack of rolling at age 2, cerebral palsy type other than
      spastic quadriparesis (odds ratio: 2.2; 95% confidence interval: 1.5-3.1), and
      preserved visual function (odds ratio: 2.4; 95% confidence interval: 1.1-5.4).
      Our ambulation charts depict the probability of remaining nonambulatory,
      transitioning to 1 of 3 possible ambulatory states, or expiring at all subsequent
      ages through age 14. CONCLUSION: The ambulation charts provide a simple
      straightforward way to estimate the probability that a child with cerebral palsy
      who is nonambulatory at 2 to 3 12 years of age will eventually walk with or
      without support.

PMID- 15520107
TI  - Health care preferences and priorities of adolescents with chronic illnesses.
AB  - BACKGROUND: Efforts to make health care for adolescents with chronic illnesses
      more patient-centered must be grounded in an understanding and clear measures of
      adolescents' preferences and priorities. OBJECTIVE: To develop a measure of
      health care preferences of adolescents with chronic illnesses and to determine
      demographic, developmental, and health factors associated with adolescents'
      preferences. DESIGN: Mixed-method questionnaire development and survey. SETTING:
      Subspecialty clinics of a tertiary care children's hospital. PARTICIPANTS: All
      adolescents (age: 11-19 years) with juvenile rheumatoid arthritis, sickle cell
      disease, inflammatory bowel disease, or cystic fibrosis of at least 2-year
      duration who were being treated at the participating center were eligible to
      participate, and 155 of 251 did so (62%). The participants had a mean age of 15.5
      +/- 2.4 years, 45% were male, and 75% were white. INTERVENTION: None. MAIN
      OUTCOME MEASURES: Ratings of 65 items related to quality of care and 17 items
      related to physician-patient communication styles. RESULTS: An 82-item
      questionnaire, devised from qualitative analysis of focus group results,
      contained 65 Likert scale items that adolescents considered important for health
      care quality and 17 forced-choice items related to adolescents' preferences for
      communication. Among the first 65 items, the group of questions related to
      physician trust and respect had the highest rating of 5.24 +/- 0.62 of 6,
      followed by patient power and control (mean rating: 4.72 +/- 0.77) and then
      caring and closeness in the patient-doctor relationship (mean rating: 4.19 +/-
      0.91). For the communication items, the adolescents, on average, preferred
      communication directly to them rather than to their parents and were nearly
      neutral regarding physicians' inquiries about personal issues. CONCLUSIONS:
      Participants rated aspects of interpersonal care (especially honesty, attention
      to pain, and items related to respect) as most important in their judgments of
      quality. As in most previous studies of adults, technical aspects of care were
      also rated highly, suggesting that adolescents understand and value both
      scientific and interpersonal aspects of care.

PMID- 15520108
TI  - Pediatric Crohn's disease and growth retardation: the role of genotype,
      phenotype, and disease severity.
AB  - BACKGROUND: Delayed growth is a well-established feature of pediatric Crohn's
      disease. Several factors have been shown to affect growth, including disease
      location, severity, and treatment. The recently discovered NOD2 gene has been
      correlated to ileal location of Crohn's disease and subsequently could affect
      growth through the resulting phenotype or as an independent risk factor. The aim
      of our study was to determine if growth retardation is affected by genotype
      independently of disease location or severity. METHODS: Genotyping for 3 NOD2
      single-nucleotide polymorphisms was performed in 93 patients with detailed growth
      records. Parameters including disease location, disease severity, and NOD 2
      genotype and their effect on z scores for height and weight at disease onset and
      during follow-up were analyzed. RESULTS: NOD2 mutations were correlated with
      ileal location but not with disease severity or growth retardation. Ileal
      involvement was significantly associated with height retardation at disease onset
      and the lowest z score during follow-up. Use of steroids affected weight but not
      height. Regression models for growth variables revealed that the strongest
      association with impaired growth is with disease severity (weight- and height
      failure odds ratios: 6.17 and 4.52, respectively). CONCLUSIONS: Severity of
      disease is correlated with growth failure for both height and weight. Location of
      disease is a weaker predictor of disordered growth and is correlated with growth
      retardation but not growth failure. The NOD2 genotype was not correlated with
      growth retardation or growth failure.

PMID- 15520110
TI  - Long-term pulmonary sequelae in children who were treated with extracorporeal
      membrane oxygenation for neonatal respiratory failure.
AB  - OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) is a life-saving therapy
      for neonates with intractable respiratory failure, but the long-term pulmonary
      outcome is unknown. Our aim was to investigate the long-term pulmonary sequelae
      of these children. STUDY DESIGN: We studied 50 children at 11.1 +/- 1.1 years
      (mean +/- SD) who had been treated with neonatal ECMO for meconium aspiration
      syndrome (38%), sepsis (18%), sepsis with pneumonia (12%), congenital
      diaphragmatic hernia (12%), congenital heart disease (8%), persistent pulmonary
      hypertension of the newborn (6%), and respiratory distress syndrome (4%) and 27
      healthy controls (10.8 +/- 1.6 years). All subjects completed a respiratory
      questionnaire and performed pulmonary function and graded cardiopulmonary
      exercise testing. RESULTS: Neonatal ECMO survivors had hyperinflation (median
      residual volume: 131%), airway obstruction (median forced expired volume in 1
      second: 79%), lower oxygen saturation with exercise, and lower peak oxygen
      consumption than controls. The ECMO group achieved similar exercise minute
      ventilation to controls, with more rapid and shallow breathing. ECMO survivors
      had an increased frequency of exercise-induced bronchospasm. Those who required
      higher inspired oxygen tension and ventilator pressures after weaning from ECMO
      had lower forced expired volume in 1 second and oxygen saturation values.
      CONCLUSION: Neonatal ECMO survivors experience lung injury lasting into later
      childhood. Lung dysfunction correlates with the extent and duration of barotrauma
      and oxygen exposure as neonates.

PMID- 15520109
TI  - Neurodevelopmental outcome and growth at 18 to 22 months' corrected age in
      extremely low birth weight infants treated with early erythropoietin and iron.
AB  - BACKGROUND: Clinical trials evaluating the use of erythropoietin (Epo) have
      demonstrated a limited reduction in transfusions; however, long-term
      developmental follow-up data are scarce. OBJECTIVE: We compared anthropometric
      measurements, postdischarge events, need for transfusions, and developmental
      outcomes at 18 to 22 months' corrected age in extremely low birth weight (ELBW)
      infants treated with early Epo and supplemental iron therapy with that of
      placebo/control infants treated with supplemental iron alone. METHODS: The
      National Institute of Child Health and Human Development Neonatal Research
      Network completed a randomized, controlled trial of early Epo and iron therapy in
      preterm infants < or =1250 g. A total of 172 ELBW (< or =1000-g birth weight)
      infants were enrolled (87 Epo and 85 placebo/control). Of the 72 Epo-treated and
      70 placebo/control ELBW infants surviving to discharge, follow-up data (growth,
      development, rehospitalization, transfusions) at 18 to 22 months' corrected age
      were collected on 51 of 72 Epo-treated infants (71%) and 51 of 70
      placebo/controls (73%) by certified examiners masked to the treatment group.
      Statistical significance was determined using chi2 analysis. RESULTS: There were
      no significant differences between treatment groups in weight or length or in the
      percentage of infants weighing <10th percentile either at the time of discharge
      or at follow-up, and no difference was found in the mean head circumference
      between groups. A similar percentage of infants in each group was rehospitalized
      (38% Epo and 35% placebo/control) for similar reasons. There were no differences
      between groups with respect to the percentage of infants with Bayley-II Mental
      Developmental Index <70 (34% Epo and 36% placebo/control), blindness (0% Epo and
      2% placebo/control), deafness or hearing loss requiring amplification (2% Epo and
      2% placebo/control), moderate to severe cerebral palsy (16% Epo and 18%
      placebo/control) or the percentage of infants with any of the above-described
      neurodevelopmental impairments (42% Epo and 44% placebo/control). CONCLUSIONS:
      Treatment of ELBW infants with early Epo and iron does not significantly
      influence anthropometric measurements, need for rehospitalization, transfusions
      after discharge, or developmental outcome at 18 to 22 months' corrected age.

PMID- 15520111
TI  - Brain-type natriuretic peptide in the diagnosis and management of persistent
      pulmonary hypertension of the newborn.
AB  - OBJECTIVE: The diagnosis of persistent pulmonary hypertension (PPHN) can often be
      difficult to make, especially in a clinical setting in which pediatric
      echocardiography is not readily available. A noninvasive test that could
      differentiate PPHN from other cardiorespiratory disease would be very useful in
      the early management of the disease, because it would allow rapid identification
      of those infants at greatest risk of requiring the services of a level 3 nursery.
      Brain-type natriuretic peptide (BNP) is an endogenous peptide hormone secreted by
      the cardiac ventricles in response to increased wall stress and related
      ventricular filling pressures. The purpose of this study was to determine if BNP
      levels are elevated in newborns with PPHN and therefore may be used as a marker
      for differentiating PPHN from other forms of respiratory disease during the early
      newborn period. METHOD: We used a prospective cohort design with 3 groups. One
      group was diagnosed with PPHN by clinical and echocardiographic criteria (PPHN
      group: n = 15). The second group had been diagnosed with respiratory disease;
      however, PPHN had been ruled out by having no evidence of elevated pulmonary
      pressure by echocardiography (RD group: n = 17). The third group had no
      respiratory disease and was breathing room air (RA group: n = 15). BNP levels
      were measured with a point-of-care fluorescence immunoassay at various time
      intervals between birth and 150 hours of life. RESULTS: There were no differences
      between groups for birth weight, gestational age, gender, race, Apgar scores at 1
      minute, or age at time of initial blood sampling. Initial BNP levels (pg/mL) were
      elevated in the PPHN group relative to both the RA and RD groups (median [25%,
      75%]: PPHN group = 1610 [1128, 1745]; RD group = 132 [76, 327]; RA group = 248
      [127, 395]). There was no difference in the initial BNP level between the RA and
      RD groups. BNP levels remained elevated in the PPHN group over both groups for
      the first 4 days of life. BNP levels correlated with the gradient of the
      tricuspid regurgitation jet and with the ratio of tricuspid regurgitation jet
      gradient to mean blood pressure. BNP levels were not affected by administration
      of dopamine or dobutamine. BNP weakly correlated with the oxygenation index but
      not with the alveolar-arterial oxygenation gradient. CONCLUSIONS: Our findings
      indicate that BNP levels are elevated in infants with PPHN but not in infants
      with other forms of respiratory distress not associated with PPHN. Elevated BNP
      levels in term or near-term infants with respiratory distress should increase the
      suspicion of PPHN. Serial determination may also be helpful in monitoring the
      clinical course of such infants.

PMID- 15520112
TI  - Impact of a physiologic definition on bronchopulmonary dysplasia rates.
AB  - OBJECTIVE: Bronchopulmonary dysplasia (BPD) is the endpoint of many intervention
      trials in neonatology, yet the outcome measure when based solely on oxygen
      administration may be confounded by differing criteria for oxygen administration
      between physicians. We previously reported a technique to standardize the
      definition of BPD between sites by using a timed room-air challenge in selected
      infants. We hypothesized that a physiologic definition of BPD would reduce the
      variation in observed rates of BPD among different neonatal centers. Methodology.
      A total of 1598 consecutive inborn premature infants (501-1249 g birth weight)
      who remained hospitalized at 36 weeks' postmenstrual age were prospectively
      assessed and assigned an outcome with both a clinical definition and physiologic
      definition of BPD. The clinical definition of BPD was oxygen supplementation at
      exactly 36 weeks' postmenstrual age. The physiologic definition of BPD was
      assigned at 36 +/- 1 weeks' postmenstrual age and included 2 distinct
      subpopulations. First, neonates on positive pressure support or receiving >30%
      supplemental oxygen with saturations between 90% and 96% were assigned the
      outcome BPD and not tested further. Second, those receiving < or =30% oxygen or
      effective oxygen >30% with saturations >96% underwent a room-air challenge with
      continuous observation and oxygen-saturation monitoring. Outcomes of the room-air
      challenge were "no BPD" (saturations > or =90% during weaning and in room air for
      30 minutes) or "BPD" (saturation <90%). At the conclusion of the room-air
      challenge, all infants were returned to their baseline oxygen levels. Safety
      (apnea, bradycardia, increased oxygen use) and outcomes of the physiologic
      definition versus the clinical definition were assessed. RESULTS: A total of 560
      (35.0%) neonates were diagnosed with BPD by the clinical definition of oxygen use
      at 36 weeks' postmenstrual age. The physiologic definition diagnosed BPD in 398
      (25.0%) neonates in the cohort. All infants were safely studied. There were
      marked differences in the impact of the definition on BPD rates between centers
      (mean reduction: 10%; range: 0-44%). Sixteen centers had a decrease in their BPD
      rate, and 1 center had no change in their rate. CONCLUSIONS: The physiologic
      definition of BPD reduced the overall rate of BPD and reduced the variation among
      centers. Significant center differences in the impact of the physiologic
      definition were seen, and differences remained even with the use of this
      standardized definition. The magnitude of the change in BPD rate is comparable to
      the magnitude of treatment effects seen in some clinical trials in BPD. The
      physiologic definition of BPD facilitates the measurement of BPD as an outcome in
      clinical trials and the comparison between and within centers over time.

PMID- 15520113
TI  - Griseofulvin versus terbinafine in the treatment of tinea capitis: a meta
      analysis of randomized, clinical trials.
AB  - OBJECTIVE: Tinea capitis, a common pediatric infection in the United States, is
      caused mainly by Trichophyton species and affects many urban children. Although
      the current treatment of choice is oral griseofulvin, terbinafine has been shown
      to be variably effective in several comparative, randomized trials. The purpose
      of this study was to perform a meta-analysis of randomized, clinical trials
      comparing the efficacies of oral terbinafine and oral griseofulvin for the
      treatment of childhood tinea capitis. METHODS: The Medline database was searched
      for randomized, clinical studies comparing griseofulvin and terbinafine for the
      treatment of tinea capitis. Acceptance criteria included oral administration of
      griseofulvin for at least 6 weeks and the identification of a pathogenic
      dermatophyte from the scalp at the time of enrollment in the study. Scalp culture
      status at least 8 weeks after enrollment was used as the outcome. The common odds
      ratio (OR) with 95% confidence intervals (CIs), the Cochran-Mantel-Haenszel test
      for significance, and the Breslow-Day test for homogeneity were calculated.
      RESULTS: Six articles that satisfied all inclusion criteria were identified.
      These studies were combined by using outcomes at 12 to 16 weeks after enrollment.
      The common OR was 0.86 (95% CI: 0.57-1.27). When the 5 studies that identified
      Trichophyton species as the predominant pathogen were combined, using outcomes 12
      weeks after enrollment, the results nearly favored terbinafine (OR: 0.65 [95% CI:
      0.42-1.01]). For outcomes at 8 weeks after enrollment, no difference was found
      between the agents (OR: 0.84 [95% CI: 0.54-1.32]). Consclusions.A 2- to 4-week
      course of terbinafine is at least as effective as a 6- to 8-week course of
      griseofulvin for the treatment of Trichophyton infections of the scalp.
      Griseofulvin is likely to be superior to terbinafine for the rare cases caused by
      Microsporum species.

PMID- 15520114
TI  - Providing life-saving health care to undocumented children: controversies and
      ethical issues.
AB  - Pediatricians and hospitals with special pediatric expertise are facing the
      dilemma of rationing care to uninsured, undocumented children, especially for
      expensive life-saving care such as transplants, chemotherapy, and dialysis. This
      article reviews a relevant case history and provides a review and discussion of
      the ethical and policy issues associated with this problem.

PMID- 15520115
TI  - Otitis, antibiotics, and the greater good.

PMID- 15520116
TI  - Preemptive strike in the war on pain: is it a safe strategy for our vulnerable
      infants?

PMID- 15520117
TI  - To sleep or not to sleep: that remains the question.

PMID- 15520118
TI  - Gains in children's health insurance coverage but additional progress needed.

PMID- 15520119
TI  - Levels of neonatal care.
AB  - The concept of designations for hospital facilities that care for newborn infants
      according to the level of complexity of care provided was first proposed in 1976.
      Subsequent diversity in the definitions and application of levels of care has
      complicated facility-based evaluation of clinical outcomes, resource allocation
      and utilization, and service delivery. We review data supporting the need for
      uniform nationally applicable definitions and the clinical basis for a proposed
      classification based on complexity of care. Facilities that provide hospital care
      for newborn infants should be classified on the basis of functional capabilities,
      and these facilities should be organized within a regionalized system of
      perinatal care.

PMID- 15520120
TI  - Relief of pain and anxiety in pediatric patients in emergency medical systems.
AB  - Whether a component of a disease process, the result of acute injury, or a
      product of a diagnostic or therapeutic procedure, pain should be relieved and
      stress should be decreased for pediatric patients. Control of pain and stress for
      children who enter into the emergency medical system, from the prehospital arena
      to the emergency department, is a vital component of emergency care. Any barriers
      that prevent appropriate and timely administration of analgesia to the child who
      requires emergency medical treatment should be eliminated. Although more research
      and innovation are needed, every opportunity should be taken to use available
      methods of pain control. A systematic approach to pain management and anxiolysis,
      including staff education and protocol development, can have a positive effect on
      providing comfort to children in the emergency setting.

PMID- 15520121
TI  - Injury risk of nonpowder guns.
AB  - Nonpowder guns (ball-bearing [BB] guns, pellet guns, air rifles, paintball guns)
      continue to cause serious injuries to children and adolescents. The muzzle
      velocity of these guns can range from approximately 150 ft/second to 1200
      ft/second (the muzzle velocities of traditional firearm pistols are 750 ft/second
      to 1450 ft/second). Both low- and high-velocity nonpowder guns are associated
      with serious injuries, and fatalities can result from high-velocity guns. A
      persisting problem is the lack of medical recognition of the severity of injuries
      that can result from these guns, including penetration of the eye, skin, internal
      organs, and bone. Nationally, in 2000, there were an estimated 21840 (coefficient
      of variation: 0.0821) injuries related to nonpowder guns, with approximately 4%
      resulting in hospitalization. Between 1990 and 2000, the US Consumer Product
      Safety Commission reported 39 nonpowder gun-related deaths, of which 32 were
      children younger than 15 years. The introduction of high-powered air rifles in
      the 1970s has been associated with approximately 4 deaths per year. The advent of
      war games and the use of paintball guns have resulted in a number of reports of
      injuries, especially to the eye. Injuries associated with nonpowder guns should
      receive prompt medical management similar to the management of firearm-related
      injuries, and nonpowder guns should never be characterized as toys.

PMID- 15520122
TI  - Age terminology during the perinatal period.
AB  - Consistent definitions to describe the length of gestation and age in neonates
      are needed to compare neurodevelopmental, medical, and growth outcomes. The
      purposes of this policy statement are to review conventional definitions of age
      during the perinatal period and to recommend use of standard terminology
      including gestational age, postmenstrual age, chronological age, corrected age,
      adjusted age, and estimated date of delivery.

PMID- 15520124
TI  - Review of Fomon's "assessment of growth of formula-fed infants: evolutionary
      considerations".

PMID- 15520126
TI  - The pediatric eye disease investigator group report may be too optimistic about
      efficacy of treatment.

PMID- 15520128
TI  - Meconium obstruction in the very low birth weight premature infant.

PMID- 15520130
TI  - Hospital-acquired hyponatremia is associated with excessive administration of
      intravenous maintenance fluid.

PMID- 15520131
TI  - Rebound seizures during rewarming.

PMID- 15520132
TI  - Smoking patterns among young people with asthma.

PMID- 15520133
TI  - Effect of dextromethorphan, diphenhydramine, and placebo on nocturnal cough and
      sleep quality for coughing children and their parents.

PMID- 15520134
TI  - Compassion or opportunism?

PMID- 15520135
TI  - Celiac disease in children with migraine.

PMID- 15520136
TI  - Does children's watching of television cause attention problems? Retesting the
      hypothesis in a Danish cohort.

PMID- 15520137
TI  - Adult lactose tolerance is not an advantageous evolutionary trait.

PMID- 15520140
TI  - Effectiveness of neonatal intensive care for extremely low birth weight infants.

PMID- 15520142
TI  - Comments on the Prosser et Al approach to value disease reduction in children.

PMID- 15520143
TI  - MRSA--past, present, future.

PMID- 15520144
TI  - Metabolic syndrome: maladaptation to a modern world.

PMID- 15520145
TI  - Methicillin-resistant Staphylococcus aureus in a general intensive care unit.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) has presented special problems
      in intensive care units (ICUs) because of the difficulties in implementing
      infection control measures. The prevalence and rate of acquisition of MRSA were
      studied over thirty months in a nine-bed ICU. Nasal and groin swabs were taken on
      admission and then weekly, and other cultures as clinically indicated. Of 1361
      admissions 119 were MRSA-positive on arrival. 21 cases had been identified before
      admission and the remainder were detected by screening; in 57 the positive result
      was known only after discharge. Of the 1242 admissions initially negative 68
      acquired MRSA while in the ICU. The ICU had no known MRSA-positive patients on
      185 (20.3%) of 914 days, the longest sequence being 17 days. Positive patients
      occupied 1387 (16.9%) of the 8226 available bed days. Length of stay predicted
      the risk of acquiring MRSA. Estimated from patients who completed each weekly
      screening cycle, the risk was 7.5% per week in the first week and 20.3% per week
      thereafter. The risk was not influenced by initial APACHE II score, the use of
      haemofiltration, or the number of MRSA-positive patients in the unit. The data
      suggest that a further 38 of those discharged between weekly screenings acquired
      MRSA, giving an incidence of 8.5%. MRSA was grown from blood in 17 patients, and
      from sputum in 53 (ICU-acquired in 18% and 47%). This study suggests that nearly
      10% of admissions to a general ICU will be MRSA-positive, of whom only half will
      be identified before discharge. With standard prevention the risk of previously
      negative patients acquiring MRSA approximates to 1% per day in the first week and
      3% per day thereafter, with nearly one-fifth progressing to bacteraemia; one-half
      will have MRSA in sputum. Patients with longer stays constitute a high-risk
      minority for whom additional measures such as decontamination with oropharyngeal
      and enteral vancomycin should be considered.

PMID- 15520146
TI  - Biochemical recovery time scales in elderly patients with osteomalacia.
AB  - Osteomalacia is not rare in the UK and climatically similar countries,
      particularly in elderly people and those of Asian descent. Overt clinical
      osteomalacia is usually treated with a loading dose of vitamin D, followed by a
      regular supplement. However, little is known of the time taken to reach a stable
      biochemical state after starting treatment. Such information would shed light on
      the duration of the bone remineralization phase and guide decisions on the length
      of follow-up. To address this we conducted a 2-year follow-up study of 42
      patients (35 female, mean age 80.8 years) with biopsy proven osteomalacia treated
      with a standard replacement regimen and general nutritional support. Although
      normocalcaemia was attained within 4 weeks the mean values continued to rise, to
      a mid-range plateau at 52 weeks. The phosphate and alkaline phosphatase values
      also took at least a year to reach a stable mean, with a slight further trend
      towards the mid-range for the entire 104 weeks. The mean serum albumin also rose
      throughout the first 52 weeks, indicating an effective response to the general
      nutritional support measures. Our observations suggest that the dynamic
      relationship between calcium, phosphate and bone requires at least a year, and
      probably longer, to reach an equilibrium after treatment for osteomalacia in
      elderly patients. The findings emphasize the need for close medical and social
      follow-up in this clinical context.

PMID- 15520147
TI  - What happens when children with attention deficit/hyperactivity disorder grow up?

PMID- 15520148
TI  - Methotrexate toxicity induced by acute renal failure.

PMID- 15520149
TI  - Cerebellar atrophy in systemic sclerosis.

PMID- 15520150
TI  - Cryptogenic multifocal ulcerous stenosing enteritis.

PMID- 15520151
TI  - A tense case--Carney's triad.

PMID- 15520152
TI  - Unsuspected acquired haemophilia in a patient with myocardial infarction.

PMID- 15520153
TI  - Appendicitis after appendicectomy.

PMID- 15520154
TI  - Child and adolescent psychiatry--a model for medical teaching.

PMID- 15520156
TI  - Camptodactyly in a painting by Dirk Bouts (c. 1410-1475).

PMID- 15520157
TI  - Helmets for cyclists and the ethics of legislation.

PMID- 15520158
TI  - Medical abbreviations.

PMID- 15520159
TI  - Home or hospital: choices at the end of life.

PMID- 15520160
TI  - Medical care in France.

PMID- 15520161
TI  - Access to scrotal ultrasonography.

PMID- 15520162
TI  - Aberrant and alternative splicing in cancer.
AB  - Pre-mRNA splicing is a sophisticated and ubiquitous nuclear process, which is a
      natural source of cancer-causing errors in gene expression. Intronic splice site
      mutations of tumor suppressor genes often cause exon-skipping events that
      truncate proteins just like classical nonsense mutations. Also, many studies over
      the last 20 years have reported cancer-specific alternative splicing in the
      absence of genomic mutations. Affected proteins include transcription factors,
      cell signal transducers, and components of the extracellular matrix. Antibodies
      against alternatively spliced products on cancer cells are currently in clinical
      trials, and competitive reverse transcription-PCR across regions of alternative
      splicing is being used as a simple diagnostic test. As well as being associated
      with cancer, the nature of the alternative gene products is usually consistent
      with an active role in cancer; therefore, the alternative splicing process itself
      is a potential target for gene therapy.

PMID- 15520163
TI  - PTEN up-regulates the tumor metastasis suppressor gene Drg-1 in prostate and
      breast cancer.
AB  - PTEN (phosphatase and tensin homologue deleted on chromosome 10) has been shown
      to be inactivated in a wide variety of cancers, and the role of this gene as a
      tumor suppressor has been well established. On the other hand, results of recent
      animal studies as well as clinical evidence indicate that PTEN is also involved
      in tumor metastasis suppression. Although PTEN is known to play a key role in
      controlling cell growth and apoptosis, how PTEN exerts the metastasis suppressor
      function remains largely unknown. Recently, a microarray analysis identified the
      Drg-1 gene (differentiation related gene 1) as one of the potential targets of
      PTEN. The Drg-1 gene has been shown to suppress tumor metastasis in animal models
      of prostate and colon cancer, and the expression of this gene is significantly
      reduced with advancement of prostate and breast cancers in clinical setting. In
      this study, we explored the possibility that PTEN controls tumor metastasis by
      regulating the expression of the Drg-1 gene. Our results indicate that
      overexpression of PTEN significantly augments the endogenous expression of Drg-1
      protein, whereas inhibition of PTEN by small interfering RNA decreases Drg-1 in a
      dose- and time-dependent manner. We also found that the control of the Drg-1 gene
      by PTEN seems to be at the transcriptional level, and that a phospho-Akt
      inhibitor restores the Drg-1 expression, indicating that PTEN controls Drg-1 by
      an Akt-dependent pathway. Consistent with these results, our immunohistochemical
      analysis revealed that PTEN expression correlates significantly with Drg-1 in
      both prostate and breast cancer cases. Furthermore, combination of the two
      markers, PTEN and Drg-1, emerged as a significantly better predictor of prostate
      and breast cancer patient survival than either marker alone.

PMID- 15520164
TI  - Gene silencing in androgen-responsive prostate cancer cells from the tissue
      specific prostate-specific antigen promoter.
AB  - The success of gene therapy using a RNA interference approach relies on small
      interfering RNA (siRNA) expression from a highly tissue-specific RNA polymerase
      II promoter rather than from ubiquitous RNA polymerase III. Accordingly, we have
      developed a prostate-specific vector that expresses siRNAs from the human
      prostate-specific antigen promoter, a RNA polymerase II promoter. Our data
      demonstrate androgen-dependent and tissue-specific siRNA-mediated gene silencing
      in the androgen-responsive prostate cancer cell line, LNCaP. The biological
      significance was evidenced by altered apoptotic activity through the inhibition
      of the apoptosis-related regulatory gene. These results demonstrate that siRNA
      mediated gene silencing from a tissue-specific RNA polymerase II promoter could
      be a potential tool for tissue-specific gene therapy.

PMID- 15520165
TI  - Breast cancer cells isolated by chemotaxis from primary tumors show increased
      survival and resistance to chemotherapy.
AB  - In this study, we have collected a migratory population of carcinoma cells by
      chemotaxis to epidermal growth factor-containing microneedles held in the primary
      tumor. The collected cells were subjected to microarray analysis for differential
      gene expression. The results show that anti-apoptotic genes are up-regulated and
      pro-apoptotic genes are down-regulated coordinately in the migratory
      subpopulation. Induction of apoptosis by doxorubicin, cisplatin, and etoposide in
      these cells demonstrates that they exhibit a lower drug-induced apoptotic index
      and lower cell death compared with carcinoma cells of the whole tumor. Our study
      indicates, for the first time, the capability of using a rat alograft model for
      evaluating the apoptotic status of a migratory subpopulation of tumor cells and
      the ability to study their resistance to chemotherapeutic agents directly. In
      addition, these results indicate that tumor cells that are chemotactic and
      migratory in response to epidermal growth factor in the primary tumor have a
      survival advantage over stationary tumor cells.

PMID- 15520166
TI  - Nanoparticle-aptamer bioconjugates: a new approach for targeting prostate cancer
      cells.
AB  - Nucleic acid ligands (aptamers) are potentially well suited for the therapeutic
      targeting of drug encapsulated controlled release polymer particles in a cell- or
      tissue-specific manner. We synthesized a bioconjugate composed of controlled
      release polymer nanoparticles and aptamers and examined its efficacy for targeted
      delivery to prostate cancer cells. Specifically, we synthesized poly(lactic acid)
      block-polyethylene glycol (PEG) copolymer with a terminal carboxylic acid
      functional group (PLA-PEG-COOH), and encapsulated rhodamine-labeled dextran (as a
      model drug) within PLA-PEG-COOH nanoparticles. These nanoparticles have the
      following desirable characteristics: (a) negative surface charge (-50 +/- 3 mV,
      mean +/- SD, n = 3), which may minimize nonspecific interaction with the
      negatively charged nucleic acid aptamers; (b) carboxylic acid groups on the
      particle surface for potential modification and covalent conjugation to amine
      modified aptamers; and (c) presence of PEG on particle surface, which enhances
      circulating half-life while contributing to decreased uptake in nontargeted
      cells. Next, we generated nanoparticle-aptamer bioconjugates with RNA aptamers
      that bind to the prostate-specific membrane antigen, a well-known prostate cancer
      tumor marker that is overexpressed on prostate acinar epithelial cells. We
      demonstrated that these bioconjugates can efficiently target and get taken up by
      the prostate LNCaP epithelial cells, which express the prostate-specific membrane
      antigen protein (77-fold increase in binding versus control, n = 150 cells per
      group). In contrast to LNCaP cells, the uptake of these particles is not enhanced
      in cells that do not express the prostate-specific membrane antigen protein. To
      our knowledge, this represents the first report of targeted drug delivery with
      nanoparticle-aptamer bioconjugates.

PMID- 15520167
TI  - A novel nuclear protein, MGC5306 interacts with DNA polymerase beta and has a
      potential role in cellular phenotype.
AB  - A novel protein MGC5306 has been identified in yeast-two-hybrid analysis by
      screening a HeLa cDNA library with a truncated DNA polymerasebeta (polbetaDelta)
      as bait. The polbetaDelta is expressed in various types of cancers. Co
      immunoprecipitation-Western blot analysis confirms not only its interaction with
      polbetaDelta but also with wild-type polbeta. Binding to polbeta indicates
      potential function of MGC5306 in repair pathway. Transfection of cells with
      MGC5306-GFP and Western blot analysis with anti-MGC5306 antibody reveal its
      nuclear localization. MGC5306 is expressed in human carcinomas and tumor cell
      lines but not in normal tissues, suggesting MGC5306 is most likely involved in
      carcinogenesis. An antigrowth activity and modulations of cell cycle events are
      identified in cells expressing siRNAMGC5306.

PMID- 15520168
TI  - Mutation of the PIK3CA gene in ovarian and breast cancer.
AB  - Phosphatidylinositol 3'-kinases are lipid kinases with important roles in
      neoplasia. Recently, a very high frequency of somatic mutations in PIK3CA has
      been reported among a large series of colorectal cancers. However, the relevance
      of PIK3CA mutation in other cancer types remains unclear because of the limited
      number of tumors investigated. We have screened a total of 284 primary human
      tumors for mutations in all coding exons of PIK3CA using a combination of single
      stranded conformational polymorphism and denaturing high-performance liquid
      chromatography analysis. Among 70 primary breast cancers, 40% (28 of 70) harbored
      mutations in PIK3CA, making it the most common mutation described to date in this
      cancer type. Mutations were not associated with histologic subtype, estrogen
      receptor status, grade or presence of tumor in lymph nodes. Among the primary
      epithelial ovarian cancers only 11 of 167 (6.6%) contain somatic mutations, but
      there was a clear histologic subtype bias in their distribution. Only 2 of 88
      (2.3%) of serous carcinomas had PIK3CA mutations compared with 8 of 40 (20.0%)
      endometrioid and clear cell cancers, which was highly significant (P = 0.001). In
      contrast, PIK3CA gene amplification (>7-fold) was common among all histologic
      subtypes (24.5%) and was inversely associated with the presence of mutations.
      Overall, PIK3CA mutation or gene amplification was detected in 30.5% of all
      ovarian cancers and 45% of the endometrioid and clear cell subtypes. Our study is
      the first direct evidence that PIK3CA is an oncogene in ovarian cancer and
      greatly extends recent findings in breast cancer.

PMID- 15520169
TI  - Androgenic suppression of ATP-binding cassette transporter A1 expression in LNCaP
      human prostate cancer cells.
AB  - Alteration of lipid metabolism is commonly observed in sex hormone-dependent
      cancer cells, yet its mechanistic involvement in cancer cell proliferation and
      progression is unclear. We have found that the expression of the cholesterol
      transporter, ATP-binding cassette transporter A1 (ABCA1), was 15- to 20-fold
      higher in androgen-dependent than in androgen-independent LNCaP human prostate
      cancer cells, indicating a possible relationship between the expression levels of
      ABCA1 and prostate cancer progression. On the basis of real-time quantitative PCR
      and Western blot analysis, expression of ABCA1 in androgen-dependent cells was
      inhibited by androgen. The antiandrogen Casodex blocked the effect of androgen,
      implicating the androgen receptor in regulation of ABCA1 expression by androgens.
      Using an ABCA1 promoter-reporter gene assay, androgenic suppression was observed
      at the transcriptional level in androgen-dependent but not in androgen
      independent prostate cancer cells. ABCA1 appears to have a role in modulating
      cell proliferation because knockdown of ABCA1 expression by RNA interference in
      androgen-dependent cells increased their rate of proliferation. Therefore, a
      suppressive effect of androgen on ABCA1 expression may be one of the mechanisms
      by which androgens regulate proliferation in prostate cancer cells. Attenuated
      ABCA1 expression in androgen-independent cells thus may contribute, in part, to
      prostate cancer progression.

PMID- 15520170
TI  - Antiproliferative effect of liver X receptor agonists on LNCaP human prostate
      cancer cells.
AB  - Liver X receptors function as central transcriptional regulators for lipid
      homeostasis, for which agonists have been developed as potential drugs for
      treatment of cardiovascular diseases and metabolic syndromes. Because
      dysregulation of lipid metabolism has been implicated in sex hormone-dependent
      cancers, we investigated the effect of liver X receptor agonists on prostate and
      breast cancer cell proliferation. Treatment of human prostate cancer LNCaP cell
      lines with the synthetic liver X receptor agonist T0901317 decreased the
      percentage of S-phase cells in a dose-dependent manner and increased the
      expression of cyclin-dependent kinase inhibitor p27(Kip-1) (p27). Knockdown of
      p27 by RNA interference blocks T0901317-induced growth inhibition, suggesting
      that p27 expression plays a crucial role in this signaling. Liver X receptor
      agonists also inhibited the proliferation of other prostate and breast cancer
      cell lines. The level of liver X receptor alpha expression correlated directly
      with sensitivity to growth inhibition by liver X receptor agonists. Retroviral
      expression of liver X receptor alpha in human breast cancer MDA-MB435S cells,
      which express low levels of endogenous liver X receptors and are insensitive to
      T0901317, sensitized these cells to T0901317. Consistent with our observations in
      LNCaP cells, T0901317 induces dramatic up-regulation of p27 in liver X receptor
      alpha-overexpressing MDA-MB435S cells. Furthermore, oral administration of
      T0901317 inhibited the growth of LNCaP tumors in athymic nude mice. Based on
      these results, modulation of the liver X receptor signaling pathway is a new
      target for controlling tumor cell proliferation; therefore, liver X receptor
      agonists may have utility as antitumorigenic agents.

PMID- 15520171
TI  - Activin type II receptor restoration in ACVR2-deficient colon cancer cells
      induces transforming growth factor-beta response pathway genes.
AB  - The activin type II receptor (ACVR2) gene is a putative tumor suppressor gene
      that is frequently mutated in microsatellite-unstable colon cancers (MSI-H colon
      cancers). ACVR2 is a member of the transforming growth factor (TGF)-beta type II
      receptor (TGFBR2) family and controls cell growth and differentiation. SMAD
      proteins are major intracellular effectors shared by ACVR2 and TGFBR2 signaling;
      however, additional shared effector mechanisms remain to be explored. To discover
      novel mechanisms transmitting the ACVR2 signal, we restored ACVR2 function by
      transfecting wild-type ACVR2 (wt-ACVR2) into a MSI-H colon cancer cell line
      carrying an ACVR2 frameshift mutation. The effect of ACVR2 restoration on cell
      growth, SMAD phosphorylation, and global molecular phenotype was then evaluated.
      Decreased cell growth was observed in wt-ACVR2 transfectants relative to ACVR2
      deficient vector-transfected controls. Western blotting revealed higher
      expression of phosphorylated SMAD2 in wt-ACVR2 transfectants versus controls,
      suggesting cells deficient in ACVR2 had impaired SMAD signaling. Microarray-based
      differential expression analysis revealed substantial ACVR2-induced
      overexpression of genes implicated in the control of cell growth and
      tumorigenesis, including the activator protein (AP)-1 complex genes JUND, JUN,
      and FOSB, as well as the small GTPase signal transduction family members, RHOB,
      ARHE, and ARHGDIA. Overexpression of these genes is shared with TGFBR2
      activation. This observed similarity between the activin and TGF-beta signaling
      systems suggests that activin may serve as an alternative activator of TGF-beta
      effectors, including SMADs, and that frameshift mutation of ACVR2 may contribute
      to MSI-H colon tumorigenesis via disruption of alternate TGF-beta effector
      pathways.

PMID- 15520173
TI  - Tumor cells fail to trans-induce telomerase in human umbilical vein endothelial
      cell cultures.
AB  - The shortening of the telomeres that occurs in most somatic cells and
      untransformed cell cultures is considered a hallmark of cellular senescence. Re
      activation of telomerase, which is usually present in immortal cells, avoids
      telomere shortening and considerably extends the culture life span. Normal human
      endothelial cells are characterized by an accelerated rate of telomere shortening
      and reach replicative senescence after a limited number of cell divisions. It has
      recently been reported that human telomerase reverse transcriptase expression may
      be strongly up-regulated in human endothelial cells cocultivated with tumor
      cells. Due to the important implications of this finding on tumor progression, we
      have extensively analyzed for the presence of telomerase in primary human
      endothelial cells either cocultivated with tumor cells or grown with tumor
      conditioned medium. We found modest, but readily detectable, amounts of
      telomerase in all human endothelial cell cultures analyzed that disappeared as
      the cultures approached senescence. Quantitative reverse transcription-PCR also
      showed a direct correlation between human telomerase reverse transcriptase
      expression and the proliferative index of the cultures. Nevertheless, we did not
      find any evidence of induction of telomerase activity by tumor cells in any of
      the tested conditions. All data indicate that telomerase in human endothelial
      cells follows an activation program that is strictly associated to the culture
      growth rate.

PMID- 15520172
TI  - CXC chemokine receptor 3 expression by activated CD8+ T cells is associated with
      survival in melanoma patients with stage III disease.
AB  - Despite the presence of tumor Ag-specific CD8(+) T cells in the peripheral blood,
      metastatic melanoma often evades immune-mediated destruction. Even after
      therapeutic efforts to expand Ag-specific T-cell populations, the correlation
      between magnitude of response and clinical efficacy has been weak. Because the
      migratory phenotype of tumor Ag-specific effector T cells may determine their
      ability for tumor control, we hypothesized that the expression of CC or CXC
      chemokine receptor (CCR) molecules on activated CD8(+) T cells may define
      phenotypes associated with more effective control of melanoma progression and
      prolonged survival. In a retrospective evaluation of patient isolates, CCR
      expression was determined for activated CD8(+) T cells derived from the
      peripheral blood or tumor-involved lymph nodes of 52 patients with stage III or
      IV metastatic melanoma. In patients with stage III disease, expression of CXCR3
      by CD8(+)CD45RO(+) cells was significantly associated with enhanced survival.
      This was a stage-specific effect, because it was not observed in patients with
      stage IV disease. In addition, CCR4 and CXCR3 were highly coexpressed and
      associated with enhanced survival in stage III patients; however, CXCR3 seems to
      be the dominant receptor associated with clinical outcome. These findings support
      the hypothesis that the host immune system affects cancer progression and
      control, and that measures of CCR status of circulating lymphocytes may have
      prognostic value.

PMID- 15520174
TI  - Overexpression of histone deacetylase 1 confers resistance to sodium butyrate
      mediated apoptosis in melanoma cells through a p53-mediated pathway.
AB  - Melanoma cells typically express wild-type p53, yet they are notoriously
      resistant to DNA-damaging agents. Here, we show that sodium butyrate (NaB), a
      histone deacetylase (HDAC) inhibitor, induced apoptosis in human melanoma cells
      in a dose- and time-dependent manner. Apoptosis was associated with HDAC1
      dependent induction of Bax and acetylation of p53. Down-regulation of HDAC1 by an
      antisense vector sensitized the cells to NaB-induced apoptosis, whereas its
      overexpression conferred resistance to this agent. Increased HDAC1 levels and
      activity impaired NaB-mediated activation of Bax promoter and Bax protein levels.
      Finally, using p53-null melanoma cell line and RNA interference in cells
      expressing wild-type p53 protein, we show that Bax induction and NaB-mediated
      apoptosis is p53 dependent.

PMID- 15520176
TI  - Activation of the BCL2 promoter in response to Hedgehog/GLI signal transduction
      is predominantly mediated by GLI2.
AB  - Aberrant activation of the Hedgehog (HH)/GLI signaling pathway has been
      implicated in the development of basal cell carcinoma (BCC). The zinc finger
      transcription factors GLI1 and GLI2 are considered mediators of the HH signal in
      epidermal cells, although their tumorigenic nature and their relative
      contribution to tumorigenesis are only poorly understood. To shed light on the
      respective role of these transcription factors in epidermal neoplasia, we
      screened for genes preferentially regulated either by GLI1 or GLI2 in human
      epidermal cells. We show here that expression of the key antiapoptotic factor
      BCL2 is predominantly activated by GLI2 compared with GLI1. Detailed promoter
      analysis and gel shift assays identified three GLI binding sites in the human
      BCL2 cis-regulatory region. We found that one of these binding sites is critical
      for conferring GLI2-specific activation of the human BCL2 promoter and that the
      selective induction of BCL2 expression depends on the zinc finger DNA binding
      domain of GLI2. In vivo, GLI2 and BCL2 were coexpressed in the outer root sheath
      of hair follicles and BCC and in plasma cells that infiltrated BCC tumor islands.
      On the basis of the latter observation, we analyzed plasma cell-derived tumors
      and found strong expression of GLI2 and BCL2 in neoplastic cells of plasmacytoma
      patients, implicating HH/GLI signaling in the development of plasma cell-derived
      malignancies. The results reveal a central role for GLI2 in activating the
      prosurvival factor BCL2, which may represent an important mechanism in the
      development or maintenance of cancers associated with inappropriate HH signaling.

PMID- 15520175
TI  - Epidermal growth factor receptor regulates aberrant expression of insulin-like
      growth factor-binding protein 3.
AB  - Epidermal growth factor receptor (EGFR) is frequently overexpressed in esophageal
      carcinoma and its precursor lesions. To gain insights into how EGFR
      overexpression affects cellular functions in primary human esophageal cells, we
      performed gene expression profiling and identified insulin-like growth factor
      binding protein (IGFBP)-3 as the most up-regulated gene. IGFBP-3 regulates cell
      proliferation through both insulin-like growth factor-dependent and independent
      mechanisms. We found that IGFBP-3 mRNA and protein expression was increased in
      EGFR-overexpressing primary and immortalized human esophageal cells. IGFBP-3 was
      also up-regulated in EGFR-overexpressing cells in organotypic culture and in EGFR
      transgenic mice. Furthermore, IGFBP-3 mRNA was overexpressed in 80% of primary
      esophageal squamous cell carcinomas and 60% of primary esophageal
      adenocarcinomas. Concomitant up-regulation of EGFR and IGFBP-3 was observed in
      60% of primary esophageal squamous cell carcinomas. Immunohistochemistry revealed
      cytoplasmic localization of IGFBP-3 in the preponderance of preneoplastic and
      neoplastic esophageal lesions. IGFBP-3 was also overexpressed in esophageal
      cancer cell lines at both mRNA (60%) and protein (40%) levels. IGFBP-3 secreted
      by cancer cells was capable of binding to insulin-like growth factor I.
      Functionally, epidermal growth factor appeared to regulate IGFBP-3 expression in
      esophageal cancer cell lines. Finally, suppression of IGFBP-3 by small
      interfering RNA augmented cell proliferation, suggesting that IGFBP-3 may inhibit
      tumor cell proliferation as a negative feedback mechanism. In aggregate, we have
      identified for the first time that IGFBP-3 is an aberrantly regulated gene
      through the EGFR signaling pathway and it may modulate EGFR effects during
      carcinogenesis.

PMID- 15520177
TI  - Tid1, the human homologue of a Drosophila tumor suppressor, reduces the malignant
      activity of ErbB-2 in carcinoma cells.
AB  - The ErbB-2/HER-2 receptor tyrosine kinase is overexpressed in a wide range of
      solid human tumors. The ErbB-2 gene product is a transmembrane glycoprotein
      belonging to the epidermal growth factor receptor family, and its cytoplasmic
      domain is responsible for sending the mitogenic signals into cells. We discovered
      that this domain of ErbB-2 interacts with Tid1 protein, the human counterpart of
      the Drosophila tumor suppressor Tid56, whose null mutation causes lethal
      tumorigenesis during the larval stage. Tid1 also is known as a cochaperone of
      heat shock protein 70 (HSP70) and binds to HSP70 through its conserved DnaJ
      domain. We found that increased expression of Tid1 in human mammary carcinomas
      overexpressing ErbB-2 suppresses the expression level of ErbB-2 and attenuates
      the resultant ErbB-2-dependent oncogenic extracellular signal-regulated kinase
      1/2 and big mitogen-activated protein kinase 1 signaling pathways leading to
      programmed cell death (PCD). A functional DnaJ domain of Tid1 also is required
      for its inhibition of ErbB-2 expression and the consequent PCD of carcinoma cells
      resulting from increased Tid1 expression. Importantly, ErbB-2-dependent tumor
      progression in animals is inhibited by increased expression of Tid1 in tumor
      cells. Collectively, these results suggest that Tid1 modulates the uncontrolled
      proliferation of ErbB-2-overexpressing carcinoma cells by reducing ErbB-2
      expression and as a result suppresses the ErbB-2-dependent cancerous signaling
      and tumor progression. Moreover, the cochaperonic and regulatory functions of
      Tid1 on HSP70 most likely play an essential role in this antitumor function of
      Tid1 in carcinoma cells.

PMID- 15520178
TI  - Development of gastric carcinoma from intestinal metaplasia in Cdx2-transgenic
      mice.
AB  - In the progression of chronic gastritis, gastric mucosal cells deviate from the
      normal pathway of gastric differentiation to an intestinal phenotype. Many
      epidemiologic studies have found an association between the formation of
      intestinal metaplasia and the development of gastric carcinoma. However, there is
      no direct evidence that shows intestinal metaplasia is a precursor lesion of
      gastric carcinoma, to date. We periodically examined the intestinal metaplastic
      mucosa of Cdx2-transgenic mice we have previously generated. Gastric polyps
      developed from intestinal metaplastic mucosa in all stomachs of Cdx2-transgenic
      mice examined. These gastric polyps consisted of intestinal-type adenocarcinoma
      that invaded the submucosa and muscularis propria and occasionally spread into
      the subserosa. p53 and APC gene mutations were recognized in the adenocarcinomas.
      The participation of APC and p53 gene mutations in gastric carcinogenesis from
      the intestinal metaplasia was verified by the Cdx2-transgenic mice, carrying
      Apc(Min) mutation or p53 deficiency, that developed gastric polyps much earlier
      than Cdx2 alone. We successfully showed that long-term intestinal metaplasia
      induces invasive gastric carcinoma. These results indicate that intestinal
      metaplasia itself plays a significant role in the genesis and progression of
      gastric carcinoma.

PMID- 15520180
TI  - Protein kinase C epsilon is an endogenous photosensitizer that enhances
      ultraviolet radiation-induced cutaneous damage and development of squamous cell
      carcinomas.
AB  - Chronic exposure to UV radiation (UVR), especially in the UVA (315-400 nm) and
      UVB (280-315 nm) spectrum of sunlight, is the major risk factor for the
      development of nonmelanoma skin cancer. UVR is a complete carcinogen, which both
      initiates and promotes carcinogenesis. We found that protein kinase C epsilon
      (PKCepsilon), a member of the phospholipid-dependent threonine/serine kinase
      family, is an endogenous photosensitizer, the overexpression of which in the
      epidermis increases the susceptibility of mice to UVR-induced cutaneous damage
      and development of squamous cell carcinoma. The PKCepsilon transgenic mouse
      (FVB/N) lines 224 and 215 overexpressed 8- and 18-fold PKCepsilon protein,
      respectively, over endogenous levels in basal epidermal cells. UVR exposure (1
      kJ/m(2) three times weekly) induced irreparable skin damage in high PKCepsilon
      overexpressing mouse line 215. However, the PKCepsilon transgenic mouse line 224,
      when exposed to UVR (2 kJ/m(2) three times weekly), exhibited minimum cutaneous
      damage but increased squamous cell carcinoma multiplicity by 3-fold and decreased
      tumor latency by 12 weeks. UVR exposure of PKCepsilon transgenic mice compared
      with wild-type littermates (1) elevated the levels of neither cyclobutane
      pyrimidine dimer nor pyrimidine (6-4) pyrimidone dimer, (2) reduced the
      appearance of sunburn cells, (3) induced extensive hyperplasia and increased the
      levels of mouse skin tumor promoter marker ornithine decarboxylase, and (4)
      elevated the levels of tumor necrosis factor alpha (TNFalpha) and other growth
      stimulatory cytokines, granulocyte colony-stimulating factor, and granulocyte
      macrophage colony-stimulating factor. The role of TNFalpha in UVR-induced
      cutaneous damage was evaluated using PKCepsilon transgenic mice deficient in
      TNFalpha. UVR treatment three times weekly for 13 weeks at 2 kJ/m(2) induced
      severe cutaneous damage in PKCepsilon transgenic mice (line 215), which was
      partially prevented in PKCepsilon-transgenic TNFalpha-knockout mice. Taken
      together, the results indicate that PKCepsilon signals UVR-induced TNFalpha
      release that is linked, at least in part, to the photosensitivity of PKCepsilon
      transgenic mice.

PMID- 15520179
TI  - From mice to humans: identification of commonly deregulated genes in mammary
      cancer via comparative SAGE studies.
AB  - Genetically engineered mouse mammary cancer models have been used over the years
      as systems to study human breast cancer. However, much controversy exists on the
      utility of such models as valid equivalents to the human cancer condition. To
      perform an interspecies gene expression comparative study in breast cancer we
      used a mouse model that most closely resembles human breast carcinogenesis. This
      system relies on the transplant of p53 null mouse mammary epithelial cells into
      the cleared mammary fat pads of syngeneic hosts. Serial analysis of gene
      expression (SAGE) was used to obtain gene expression profiles of normal and tumor
      samples from this mouse mammary cancer model (>300,000 mouse mammary-specific
      tags). The resulting mouse data were compared with 25 of our human breast cancer
      SAGE libraries (>2.5 million human breast-specific tags). We observed significant
      similarities in the deregulation of specific genes and gene families when
      comparing mouse with human breast cancer SAGE data. A total of 72 transcripts
      were identified as commonly deregulated in both species. We observed a systematic
      and significant down-regulation in all of the tumors from both species of various
      cytokines, including CXCL1 (GRO1), LIF, interleukin 6, and CCL2. All of the mouse
      and most human mammary tumors also displayed decreased expression of genes known
      to inhibit cell proliferation, including NFKBIA (IKBalpha), GADD45B, and CDKN1A
      (p21); transcription-related genes such as CEBP, JUN, JUNB, and ELF1; and
      apoptosis-related transcripts such as IER3 and GADD34/PPP1R15A. Examples of
      overexpressed transcripts in tumors from both species include proliferation
      related genes such as CCND1, CKS1B, and STMN1 (oncoprotein 18); and genes related
      to other functions such as SEPW1, SDFR1, DNCI2, and SP110. Importantly, abnormal
      expression of several of these genes has not been associated previously with
      breast cancer. The consistency of these observations was validated in independent
      mouse and human mammary cancer sets. This is the first interspecies comparison of
      mammary cancer gene expression profiles. The comparative analysis of mouse and
      human SAGE mammary cancer data validates this p53 null mouse tumor model as a
      useful system closely resembling human breast cancer development and progression.
      More importantly, these studies are allowing us to identify relevant biomarkers
      of potential use in human studies while leading to a better understanding of
      specific mechanisms of human breast carcinogenesis.

PMID- 15520181
TI  - Metallothionein-I/II double knockout mice are hypersensitive to lead-induced
      kidney carcinogenesis: role of inclusion body formation.
AB  - Lead is an environmental nephrotoxicant and probable human carcinogen.
      Elucidating factors predisposing populations to lead toxicity is an important
      public health issue. Recently, we found that metallothionein-I/-II double
      knockout (metallothionein-null) mice that are unable to produce the major forms
      of metallothionein do not produce lead inclusion bodies, which are thought to
      mitigate lead toxicity, and were sensitive to the subchronic toxic effects of
      lead exposure (10 weeks), showing modestly diminished renal function and
      nephromegaly compared with wild-type (WT) mice. It is unclear how this knockout
      might impact lead carcinogenesis. Thus, the effects of lead(II) acetate were
      tested in groups (n = 25) of male metallothionein-null and WT mice receiving
      drinking water with 0, 1,000, 2,000, or 4,000 parts per million lead for up to
      104 weeks. Renal proliferative lesions (adenoma and cystic tubular atypical
      hyperplasia) were much more common and more severe in lead-exposed
      metallothionein-null mice than in WT mice. A metastatic renal cell carcinoma also
      occurred in a lead-treated metallothionein-null mouse, whereas none occurred in
      WT mice. Lead-induced renal proliferative lesions showed marked overexpression of
      cyclin D1, a common feature of human renal tumors. Renal lead-containing nuclear
      inclusion bodies were frequently observed in WT mice but did not form in
      metallothionein-null mice. Metallothionein was often found associated with the
      outer portion of these inclusion bodies. Thus, the metallothionein-null mice
      cannot form renal inclusion bodies, even after protracted lead exposure, and this
      increases the carcinogenic potential of lead. Poor production of metallothionein
      may predispose human populations to lead carcinogenicity.

PMID- 15520182
TI  - Pten loss causes hypertrophy and increased proliferation of astrocytes in vivo.
AB  - Somatic mutations of PTEN are found in many types of cancers including
      glioblastoma, the most malignant astrocytic tumor. PTEN mutation occurs in 25 to
      40% of glioblastomas but is rarely observed in low-grade glial neoplasms. To
      determine the role of Pten in astrocytes and glial tumor formation, we
      inactivated Pten by a Cre-loxP approach with a GFAP-cre transgenic mouse that
      induced Cre-mediated recombination in astrocytes. Pten conditional knockout mice
      showed a striking progressive enlargement of the entire brain. Increased nuclear
      and soma size was observed in both astrocytes and neurons, which contributed in
      part to the increase in brain size. Pten-deficient astrocytes showed accelerated
      proliferation in vitro and aberrant ongoing proliferation in adult brains in
      vivo. In contrast, neurons lacking Pten did not show alterations in
      proliferation. This study shows cell-type dependent effects of Pten loss in the
      adult brain, including increased astrocyte proliferation that may render
      astroglial cells susceptible to neoplastic transformation or malignant
      progression.

PMID- 15520183
TI  - The gamma-glutamylcysteine synthetase and glutathione regulate asbestos-induced
      expression of activator protein-1 family members and activity.
AB  - Asbestos fibers cause persistent increases in activator protein-1 (AP-1) family
      member proto-oncogenes in lung epithelial and mesothelial cells that are linked
      to proliferation and cell transformation. Using lung epithelial cells, the
      progenitor cells of lung cancers, we report that crocidolite asbestos initially
      depletes intracellular glutathione followed by up-regulation of both catalytic
      and modifier subunits of gamma-glutamylcysteine synthetase. In vivo asbestos
      inhalation experiments confirm increased protein levels of gamma-glutamylcysteine
      synthetase in mouse lungs. We also show that asbestos-induced mRNA levels of
      fos/jun proto-oncogenes, fra-1 transactivation, and AP-1 to DNA binding activity
      are glutathione-dependent. Epidermal growth factor receptor activity by asbestos
      is blocked by N-acetyl-l-cysteine, suggesting that it is an initial redox
      activated event leading to downstream AP-1 proto-oncogene up-regulation. The
      overexpression of subunits of gamma-glutamylcysteine synthetase in combination
      completely blocked asbestos-induced up-regulation of AP-1 proto-oncogene
      expression. However, when overexpressed individually, the modifier subunit had
      more dramatic effects than the catalytic subunit. Our work shows that the
      glutathione-controlled redox status of the epithelial cell plays a pivotal role
      in asbestos-induced epidermal growth factor receptor and proto-oncogene
      activation as well as AP-1 activity.

PMID- 15520184
TI  - Notch1 and notch2 have opposite effects on embryonal brain tumor growth.
AB  - The role of Notch signaling in tumorigenesis can vary; Notch1 acts as an oncogene
      in some neoplasms, and a tumor suppressor in others. Here, we show that different
      Notch receptors can have opposite effects in a single tumor type. Expression of
      truncated, constitutively active Notch1 or Notch2 in embryonal brain tumor cell
      lines caused antagonistic effects on tumor growth. Cell proliferation, soft agar
      colony formation, and xenograft growth were all promoted by Notch2 and inhibited
      by Notch1. We also found that Notch2 receptor transcripts are highly expressed in
      progenitor cell-derived brain tumors such as medulloblastomas, whereas Notch1 is
      scarce or undetectable. This parallels normal cerebellar development, during
      which Notch2 is predominantly expressed in proliferating progenitors and Notch1
      in postmitotic differentiating cells. Given the oncogenic effects of Notch2, we
      analyzed its gene dosage in 40 embryonal brain tumors, detecting an increased
      copy number in 15% of cases. Notch2 gene amplification was confirmed by
      fluorescence in situ hybridization in one case with extremely high Notch2 mRNA
      levels. In addition, expression of the Notch pathway target gene Hes1 in
      medulloblastomas was associated with significantly shorter patient survival (P =
      0.01). Finally, pharmacological inhibition of Notch signaling suppresses growth
      of medulloblastoma cells. Our data indicate that Notch1 and Notch2 can have
      opposite effects on the growth of a single tumor type, and show that Notch2 can
      be overexpressed after gene amplification in human tumors.

PMID- 15520185
TI  - The SmoA1 mouse model reveals that notch signaling is critical for the growth and
      survival of sonic hedgehog-induced medulloblastomas.
AB  - To develop a genetically faithful model of medulloblastoma with increased tumor
      incidence compared with the current best model we activated the Sonic Hedgehog
      (Shh) pathway by transgenically expressing a constitutively active form of
      Smoothened in mouse cerebellar granule neuron precursors (ND2:SmoA1 mice). This
      resulted in early cerebellar granule cell hyper-proliferation and a 48% incidence
      of medulloblastoma formation. Gene expression studies showed an increase in the
      known Shh targets Gli1 and Nmyc that correlated with increasing hyperplasia and
      tumor formation. Notch2 and the Notch target gene, HES5, were also significantly
      elevated in Smoothened-induced tumors showing that Shh pathway activation is
      sufficient to induce Notch pathway signaling. In human medulloblastomas reverse
      transcription-PCR for Shh and Notch targets revealed activation of both of these
      pathways in most tumors when compared with normal cerebellum. Notch pathway
      inhibition with soluble Delta ligand or gamma secretase inhibitors resulted in a
      marked reduction of viable cell numbers in medulloblastoma cell lines and primary
      tumor cultures. Treatment of mice with D283 medulloblastoma xenografts with a
      gamma secretase inhibitor resulted in decreased proliferation and increased
      apoptosis, confirming that Notch signaling contributes to human medulloblastoma
      proliferation and survival. Medulloblastomas in ND2:SmoA1 mice and humans have
      concomitant increase in Shh and Notch pathway activities, both of which
      contribute to tumor survival.

PMID- 15520186
TI  - Cooperative autocrine and paracrine functions of granulocyte colony-stimulating
      factor and granulocyte-macrophage colony-stimulating factor in the progression of
      skin carcinoma cells.
AB  - Tumor growth and progression are critically controlled by alterations in the
      microenvironment often caused by an aberrant expression of growth factors and
      receptors. We demonstrated previously that tumor progression in patients and in
      the experimental HaCaT tumor model for skin squamous cell carcinomas is
      associated with a constitutive neoexpression of the hematopoietic growth factors
      granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony
      stimulating factor (GM-CSF), causing an autocrine stimulation of tumor cell
      proliferation and migration in vitro. To analyze the critical contribution of
      both factors to tumor progression, G-CSF or GM-CSF was stably transfected in
      factor-negative benign tumor cells. Forced expression of GM-CSF resulted in
      invasive growth and enhanced tumor cell proliferation in a three-dimensional
      culture model in vitro, yet tumor growth in vivo remained only transient.
      Constitutive expression of G-CSF, however, caused a shift from benign to
      malignant and strongly angiogenic tumors. Moreover, cells recultured from G-CSF
      transfected tumors exhibited enhanced tumor aggressiveness upon reinjection,
      i.e., earlier onset and faster tumor expansion. Remarkably, this further step in
      tumor progression was again associated with the constitutive expression of GM-CSF
      strongly indicating a synergistic action of both factors. Additionally,
      expression of GM-CSF in the transfected tumors mediated an earlier recruitment of
      granulocytes and macrophages to the tumor site, and expression of G-CSF induced
      an enhanced and persistent angiogenesis and increased the number of granulocytes
      and macrophages in the tumor vicinity. Thus both factors directly stimulate tumor
      cell growth and, by modulating the tumor stroma, induce a microenvironment that
      promotes tumor progression.

PMID- 15520187
TI  - Profiling the evolution of human metastatic bladder cancer.
AB  - Pulmonary metastases frequently develop in patients with aggressive bladder
      cancer, yet investigation of this process at the molecular level suffers from the
      poor availability of human metastatic tumor tissue and the absence of suitable
      animal models. To address this, we developed progressively more metastatic human
      bladder cancer cell lines and an in vivo bladder-cancer lung-metastasis model,
      and we successfully used these to identify genes of which the expression levels
      change according to the degree of pulmonary metastatic potential. By initially
      intravenously injecting the poorly metastatic T24T human urothelial cancer cells
      into nude mice, and then serially reintroducing and reisolating the human tumor
      cells from the resultant mouse lung tumors, three derivative human lines with
      increasingly metastatic phenotypes, designated FL1, FL2, and FL3, were
      sequentially isolated. To identify the genes associated with the most lung
      metastatic phenotype, the RNA complement from the parental and derivative cells
      was evaluated with oligonucleotide microarrays. In doing so, we found 121 genes
      to be progressively up-regulated during the transition from T24T to FL3, whereas
      43 genes were progressively down-regulated. As expected, many of the genes
      identified in these groups could, according to the ascribed functions of their
      protein product, theoretically participate in tissue invasion and metastasis. In
      addition, the magnitude of gene expression changes observed during the metastatic
      transition correlated with the in vivo propensity for earlier lung colonization
      and decreased host survival. To additionally define which genes found in the
      experimental system were of relevance to human bladder cancer lung metastasis, we
      evaluated gene expression profiles of 23 primary human bladder tumors of various
      stages and grades, and then we compared these gene expression profiles to the
      altered profiles in our model cell lines. Here we found that the expression of
      epiregulin, urokinase-type plasminogen activator (uPA), matrix metalloproteinase
      (MMP)14, and tissue inhibitor of metalloproteinase (TIMP-2) were consistently and
      progressively up-regulated when viewed as a function of tumor stage in tissues of
      patients versus the metastatic potential seen in the mouse lung model. The strong
      correlation of these four markers between the experimental and clinical
      situations helps validate this system as a useful tool for the study of lung
      metastasis and defines targets of therapy that may reduce the incidence of this
      process in patients.

PMID- 15520188
TI  - VEGF165b, an inhibitory vascular endothelial growth factor splice variant:
      mechanism of action, in vivo effect on angiogenesis and endogenous protein
      expression.
AB  - Growth of new blood vessels (angiogenesis), required for all tumor growth, is
      stimulated by the expression of vascular endothelial growth factor (VEGF). VEGF
      is up-regulated in all known solid tumors but also in atherosclerosis, diabetic
      retinopathy, arthritis, and many other conditions. Conventional VEGF isoforms
      have been universally described as proangiogenic cytokines. Here, we show that an
      endogenous splice variant, VEGF(165)b, is expressed as protein in normal cells
      and tissues and is circulating in human plasma. We also present evidence for a
      sister family of presumably inhibitory splice variants. Moreover, these isoforms
      are down-regulated in prostate cancer. We also show that VEGF(165)b binds VEGF
      receptor 2 with the same affinity as VEGF(165) but does not activate it or
      stimulate downstream signaling pathways. Moreover, it prevents VEGF(165)-mediated
      VEGF receptor 2 phosphorylation and signaling in cultured cells. Furthermore, we
      show, with two different in vivo angiogenesis models, that VEGF(165)b is not
      angiogenic and that it inhibits VEGF(165)-mediated angiogenesis in rabbit cornea
      and rat mesentery. Finally, we show that VEGF(165)b expressing tumors grow
      significantly more slowly than VEGF(165)-expressing tumors, indicating that a
      switch in splicing from VEGF(165) to VEGF(165)b can inhibit tumor growth. These
      results suggest that regulation of VEGF splicing may be a critical switch from an
      antiangiogenic to a proangiogenic phenotype.

PMID- 15520189
TI  - Smad3 knockout mice exhibit a resistance to skin chemical carcinogenesis.
AB  - It has been shown that Smad3 exerts both tumor-suppressive and -promoting roles.
      To evaluate the role of Smad3 in skin carcinogenesis in vivo, we applied a
      chemical skin carcinogenesis protocol to Smad3 knockout mice (Smad3(-/-) and
      Smad3(+/-)) and wild-type littermates (Smad3(+/+)). Smad3(-/-) mice exhibited
      reduced papilloma formation in comparison with Smad3(+/+) mice and did not
      develop any squamous cell carcinomas. Further analysis revealed that Smad3
      knockout mice were resistant to 12-O-tetradecanoylphorbol-13-acetate (TPA)
      induced epidermal hyperproliferation. Concurrently, increased apoptosis was
      observed in TPA-treated Smad3(-/-) skin and papillomas when compared with those
      of wild-type mice. Expression levels of activator protein-1 family members (c
      jun, junB, junD, and c-fos) and transforming growth factor (TGF)-alpha were
      significantly lower in TPA-treated Smad3(-/-) skin, cultured keratinocytes, and
      papillomas, as compared with Smad3(+/+) controls. Smad3(-/-) papillomas also
      exhibited reduced leukocyte infiltration, particularly a reduction of tumor
      associated macrophage infiltration, in comparison with Smad3(+/+) papillomas. All
      of these molecular and cellular alterations also occurred to a lesser extent in
      Smad3(+/-) mice as compared with Smad3(+/+) mice, suggesting a Smad3 gene dosage
      effect. Given that TGF-beta1 is a well-documented TPA-responsive gene and also
      has a potent chemotactic effect on macrophages, our study suggests that Smad3 may
      be required for TPA-mediated tumor promotion through inducing TGF-beta1
      responsive genes, which are required for tumor promotion, and through mediating
      TGF-beta1-induced macrophage infiltration.

PMID- 15520190
TI  - SUMO-1 modification of the Wilms' tumor suppressor WT1.
AB  - SUMO-1 conjugation modulates numerous cellular functions, including the
      subnuclear localization of its target proteins. The WT1 tumor suppressor encodes
      a four-zinc finger protein with distinct splicing isoforms. WT1(-KTS), encoding
      uninterrupted zinc fingers, functions as a transcription factor and has a
      diffusely nuclear distribution; WT1(+KTS), with an insertion of three amino acids
      (KTS) between zinc fingers three and four, localizes to discrete nuclear
      speckles, the function of which is unknown. Because the SUMO-1 E2-conjugating
      enzyme, Ubc9, interacts with WT1, we tested whether sumoylation modulates the
      cellular localization of WT1. We find here that both WT1 isoforms are directly
      sumoylated on lysine residues 73 and 177. Although RNA interference-mediated Ubc9
      depletion effectively suppresses WT1 nuclear speckles, a SUMO-1-deficient
      WT1(+KTS)(K73, 177R) double mutant retains localization to speckles. Thus, direct
      sumoylation of WT1 is not responsible for its cellular localization, and other
      sumoylated proteins may target WT1 to these nuclear structures. Identification of
      other components of WT1-associated speckles is likely to provide clues to their
      function.

PMID- 15520191
TI  - Ceramide promotes apoptosis in lung cancer-derived A549 cells by a mechanism
      involving c-Jun NH2-terminal kinase.
AB  - Ceramide regulates diverse signaling pathways involving cell senescence, the cell
      cycle, and apoptosis. Ceramide is known to potently activate a number of stress
      regulated enzymes, including the c-Jun NH(2)-terminal kinase (JNK). Although
      ceramide promotes apoptosis in human lung cancer-derived A549 cells, a role for
      JNK in this process is unknown. Here, we report that ceramide promotes apoptosis
      in A549 cells by a mechanism involving JNK. The JNK inhibitor SP600125 proved
      effective at protecting cells from the lethal effects of ceramide. To understand
      which JNK-mediated pathway may be involved, a number of JNK target proteins were
      examined, including the transcription factor, c-Jun, and the apoptotic regulatory
      proteins Bcl-X(L) and Bim. A549 cells exhibited basal levels of phosphorylated c
      Jun in nuclear fractions, revealing that active c-Jun is present in these cells.
      Ceramide was found to inhibit c-Jun phosphorylation, suggesting that JNK-mediated
      phosphorylation of c-Jun is not likely involved in ceramide-induced apoptosis.
      Ceramide did not promote Bcl-X(L) phosphorylation. On the other hand, ceramide
      promoted phosphorylation of Bim and induced translocation of active JNK from the
      nucleus to the cytoplasm and mitochondrial fraction. Ceramide-mediated changes in
      localization of JNK were consistent with the observed changes in phosphorylation
      status of c-Jun and Bim. Furthermore, ceramide promoted Bim translocation to the
      mitochondria. Mitochondrial localization of Bim has been shown recently to
      promote apoptosis. These results suggest that JNK may participate in ceramide
      induced apoptosis in A549 cells by a mechanism involving Bim.

PMID- 15520192
TI  - Alterations in vascular gene expression in invasive breast carcinoma.
AB  - The molecular signature that defines tumor microvasculature will likely provide
      clues as to how vascular-dependent tumor proliferation is regulated. Using
      purified endothelial cells, we generated a database of gene expression changes
      accompanying vascular proliferation in invasive breast cancer. In contrast to
      normal mammary vasculature, invasive breast cancer vasculature expresses
      extracellular matrix and surface proteins characteristic of proliferating and
      migrating endothelial cells. We define and validate the up-regulated expression
      of VE-cadherin and osteonectin in breast tumor vasculature. In contrast to other
      tumor types, invasive breast cancer vasculature induced a high expression level
      of specific transcription factors, including SNAIL1 and HEYL, that may drive gene
      expression changes necessary for breast tumor neovascularization. We demonstrate
      the expression of HEYL in tumor endothelial cells and additionally establish the
      ability of HEYL to both induce proliferation and attenuate programmed cell death
      of primary endothelial cells in vitro. We also establish that an additional
      intracellular protein and previously defined metastasis-associated gene, PRL3,
      appears to be expressed predominately in the vasculature of invasive breast
      cancers and is able to enhance the migration of endothelial cells in vitro.
      Together, our results provide unique insights into vascular regulation in breast
      tumors and suggest specific roles for genes in driving tumor angiogenesis.

PMID- 15520193
TI  - Hydrogen peroxide-mediated cytosolic acidification is a signal for mitochondrial
      translocation of Bax during drug-induced apoptosis of tumor cells.
AB  - Absence of the proapoptotic protein Bax renders tumor cells resistant to drug
      induced apoptosis. We have shown that hydrogen peroxide (H(2)O(2))-mediated
      cytosolic acidification is an effector mechanism during drug-induced apoptosis of
      tumor cells. Here, we report that Bax is critical in determining the sensitivity
      of tumor cells to H(2)O(2)-induced apoptosis. More importantly, exposure of
      colorectal carcinoma (HCT116) and leukemia cells (HL60 and CEM) to H(2)O(2) or
      its intracellular production during drug-induced apoptosis is a signal for
      mitochondrial translocation of Bax. Furthermore, we provide evidence that drug
      induced H(2)O(2)-mediated Bax translocation in tumor cells is caspase independent
      but involves cytosolic acidification. Inhibiting cytosolic acidification prevents
      Bax translocation, and contrarily enforced acidification of the intracellular
      milieu results in mitochondrial recruitment of Bax, even in the absence of a
      trigger. These findings provide a novel mechanism for mitochondrial translocation
      of Bax and directly implicate H(2)O(2)-mediated cytosolic acidification in the
      recruitment of the mitochondrial pathway during drug-induced apoptosis of tumor
      cells.

PMID- 15520194
TI  - Effects of chronic jet lag on tumor progression in mice.
AB  - Frequent transmeridian flights or predominant work at night can increase cancer
      risk. Altered circadian rhythms also predict for poor survival in cancer
      patients, whereas physical destruction of the suprachiasmatic nuclei (SCN), the
      hypothalamic circadian pacemaker, accelerates tumor growth in mice. Here we
      tested the effect of functional disruption of circadian system on tumor
      progression in a novel experimental model of chronic jet lag. B6D2F(1) mice were
      synchronized with 12 hours of light and 12 hours of darkness or underwent repeat
      8-hour advances of the light/dark cycle every 2 days before inoculation of
      Glasgow osteosarcoma. The 24-hour changes were assessed for plasma
      corticosterone, clock protein mPER1 expression in the SCN, and mRNA expression of
      clock genes mPer2 and mRev-erbalpha in liver and tumor. Time series were analyzed
      by spectral analysis and/or Cosinor. Differences were compared with analysis of
      variance (ANOVA). The 24-hour rest/activity cycle was ablated, and the rhythms of
      body temperature, serum corticosterone, and mPER1 protein expression in the SCN
      were markedly altered in jet-lagged mice as compared with controls (ANOVA, P <
      0.001 for corticosterone and P = 0.01 for mPER1). Tumor grew faster in the jet
      lagged animals as compared with controls (ANOVA, P < 0.001), whereas exposure to
      constant light or darkness had no effect (ANOVA, P = 0.66 and P = 0.8,
      respectively). The expression of mPer2 and mRev-erbalpha mRNAs in controls showed
      significant circadian rhythms in the liver (P = 0.006 and P = 0.003,
      respectively, Cosinor) and in the tumor (P = 0.04 and P < 0.001). Both rhythms
      were suppressed in the liver (P = 0.2 and P = 0.1, respectively, Cosinor) and in
      the tumor (P = 0.5) of jet-lagged mice. Altered environmental conditions can
      disrupt circadian clock molecular coordination in peripheral organs including
      tumors and play a significant role in malignant progression.

PMID- 15520195
TI  - Reduction of human metastatic breast cancer cell aggressiveness on introduction
      of either form a or B of the progesterone receptor and then treatment with
      progestins.
AB  - The sex steroid hormone progesterone (Pg) is critically involved in the
      development of the mammary gland, and it also is thought to play a role in breast
      cancer progression. However, the effect of Pg on malignant phenotypes is not
      fully understood in breast cancer. We previously reported that in Pg receptor
      (PR)-positive T47D breast cancer cells, Pg was able to counterbalance the
      stimulatory effect of estrogen or serum on proliferation and on expression level
      of Id-1, which generally stimulates cell proliferation and inhibits
      differentiation. Conversely, metastatic MDA-MB231 breast cancer cells lack PR and
      express high levels of Id-1 constitutively, and Pg showed no effect on Id
      expression, proliferation, and invasion in these cells. However, after
      introducing PR (either PR-A or PR-B) into MDA-MB231 cells, Pg inhibited the
      expression of Id-1 mRNA drastically. PR-transfected MDA-MB231 cells exhibited
      less proliferative activity after Pg treatment than parental or control MDA-MB231
      cells, an effect which correlated well with reduction of Id-1 mRNA. This
      inhibitory effect on proliferation was accompanied by p21 up-regulation and c-myc
      down-regulation. Moreover, Pg-treated PR transfectants showed significant
      morphologic change, appearing more flattened and spread out than control ethanol
      treated cells. Boyden chamber invasion assay revealed that PR-transfected MDA
      MB231 cells also lost most of their invasive properties after Pg treatment.
      Zymographic analysis revealed that Pg drastically inhibited matrix
      metalloproteinase-9 (MMP-9) activity in cells transfected with either PR-A or PR
      B. To determine whether Id-1 could act as a key mediator of the effects of Pg, we
      prepared cells transfected with Id-1 and PR. The morphologic change and p21 up
      regulation still were observed after Pg treatment. However, c-myc down-regulation
      was not observed; the proliferative and invasive activities were mostly
      recovered; and MMP-9 down-regulation could not be detected anymore. From these
      observations, we conclude that either form of the PR is sufficient to reduce the
      malignant phenotypes on treatment with Pg and that Id-1 plays an important role
      as a mediator of the effects of Pg on breast cancer cell proliferation and
      invasion.

PMID- 15520196
TI  - BRCA1 induces antioxidant gene expression and resistance to oxidative stress.
AB  - Mutations of the breast cancer susceptibility gene 1 (BRCA1), a tumor suppressor,
      confer an increased risk for breast, ovarian, and prostate cancers. To
      investigate the function of the BRCA1 gene, we performed DNA microarray and
      confirmatory reverse transcription-PCR analyses to identify BRCA1-regulated gene
      expression changes. We found that BRCA1 up-regulates the expression of multiple
      genes involved in the cytoprotective antioxidant response, including glutathione
      S-transferases, oxidoreductases, and other antioxidant genes. Consistent with
      these findings, BRCA1 overexpression conferred resistance while BRCA1 deficiency
      conferred sensitivity to several different oxidizing agents (hydrogen peroxide
      and paraquat). In addition, in the setting of oxidative stress (due to hydrogen
      peroxide), BRCA1 shifted the cellular redox balance to a higher ratio of reduced
      to oxidized glutathione. Finally, BRCA1 stimulated antioxidant response element
      driven transcriptional activity and enhanced the activity of the antioxidant
      response transcription factor nuclear factor erythroid-derived 2 like 2 [also
      called NRF2 (NFE2L2)]. The ability of BRCA1 to stimulate antioxidant response
      element-dependent transcription and to protect cells against oxidative stress was
      attenuated by inhibition of nuclear factor erythroid-derived 2 like 2. These
      findings suggest a novel function for BRCA1, i.e., to protect cells against
      oxidative stress. This function would be consistent with the postulated role of
      BRCA1 as a caretaker gene in preserving genomic integrity.

PMID- 15520197
TI  - Retinoic acid induces neuroblastoma cell death by inhibiting proteasomal
      degradation of retinoic acid receptor alpha.
AB  - To seek a novel therapeutic approach to neuroblastoma (NBL), we used three NBL
      cell lines (SK-N-DZ, NH12, and SK-N-SH) to examine the underlining molecular
      mechanisms of cellular reactions and sensitivity to all-trans-retinoic acid
      (ATRA). SK-N-DZ cells expressed relatively high levels of retinoic acid receptor
      alpha (RAR-alpha) and underwent ATRA-induced cell death that was blocked by an
      RAR-alpha antagonist. By contrast, RAR-alpha expression gradually decreased in
      NH12 and SK-N-SH cells, which did not experience increased cell death in response
      to ATRA. We report here the ubiquitin-dependent down-regulation of RAR-alpha
      expression during ATRA treatment. Our data suggest that SK-N-DZ cells have a
      defect in RAR-alpha down-regulation, resulting in sustained high expression of
      RAR-alpha that confers high sensitivity to ATRA. Accordingly, treatment with a
      proteasome inhibitor dramatically increased ATRA-induced cell death in NH12 and
      SK-N-SH cell lines. Our results reveal the crucial involvement of the RAR-alpha
      signaling pathway in NBL cell death and show that three NBL cell lines are
      differentially sensitive to ATRA. These data suggest a potential novel therapy
      for NBL involving retinoic acid treatment combined with the inhibition of RAR
      alpha degradation.

PMID- 15520198
TI  - Analysis of Wnt gene expression in prostate cancer: mutual inhibition by WNT11
      and the androgen receptor.
AB  - The Wnt signaling pathway is aberrantly activated in many tumor types, including
      those of the prostate, in which beta-catenin accumulates in cell nuclei and acts
      as a transcriptional coregulator for the androgen receptor. Because activating
      mutations in the beta-catenin gene are rare in prostate cancer, we have looked
      for altered expression of other components of the Wnt signaling pathway in
      prostate cancer cells. Here we determined the expression levels of Wnt family
      genes in cultured human prostate cells and prostate cancer cell lines. We found
      that WNT11 expression is elevated in hormone-independent prostate cancer cell
      lines. Additional analysis indicated that WNT11 expression is also elevated in
      high-grade prostatic tumors and in hormone-independent xenografts. Growth of
      hormone-dependent LNCaP cells in hormone-depleted media led to increased WNT11
      expression, which was repressed by the synthetic androgen R1881. This repression
      was inhibited by the antiandrogen bicalutamide, suggesting that androgens
      negatively regulate WNT11 expression through the androgen receptor. Expression of
      WNT11 inhibited androgen receptor transcriptional activity and cell growth in
      androgen-dependent cells but not in androgen-independent cells. WNT11 inhibited
      activation of the canonical Wnt pathway by WNT3A in HEK 293 cells and inhibited
      basal beta-catenin/Tcf transcriptional activity in LNCaP cells. However,
      expression of stabilized beta-catenin did not prevent the inhibition of androgen
      receptor transcriptional activity by WNT11. Our observations are consistent with
      a model in which androgen depletion activates WNT11-dependent signals that
      inhibit androgen-dependent but not androgen-independent cell growth.

PMID- 15520200
TI  - Luteolin inhibits vascular endothelial growth factor-induced angiogenesis;
      inhibition of endothelial cell survival and proliferation by targeting
      phosphatidylinositol 3'-kinase activity.
AB  - In an attempt to identify phytochemicals contributing to the well-documented
      preventive effect of plant-based diets on cancer incidence and mortality, we have
      previously shown that certain flavonoids inhibit in vitro angiogenesis. Here, we
      show that the flavonoid luteolin inhibited tumor growth and angiogenesis in a
      murine xenograft model. Furthermore, luteolin inhibited vascular endothelial
      growth factor (VEGF)-induced in vivo angiogenesis in the rabbit corneal assay. In
      agreement, luteolin inhibited both VEGF-induced survival and proliferation of
      human umbilical vein endothelial cells (HUVECs) with an IC(50) of about 5
      mumol/L. Luteolin inhibited VEGF-induced phosphatidylinositol 3'-kinase (PI3K)
      activity in HUVECs, and this inhibition was critical for both the antisurvival
      and antimitotic affects of the compound. Indeed, luteolin abolished VEGF-induced
      activation of Akt, a downstream target of PI3K conveying both survival and
      mitotic downstream signals. Because overexpression of a constitutively active
      form of Akt rescued HUVECs only from the antisurvival effects of luteolin, the
      result indicated that luteolin targeted mainly the survival signals of the
      PI3K/Akt pathway. With regard to its antimitotic activity, luteolin inhibited
      VEGF-induced phosphorylation of p70 S6 kinase (S6K), a downstream effector of
      PI3K responsible for G(1) progression. Indeed, VEGF-induced proliferation of
      HUVECs was sensitive to rapamycin, an inhibitor of p70 S6K activation.
      Surprisingly, luteolin did not affect VEGF-induced phosphorylation of
      extracellular signal-regulated kinase 1/2 mitogen-activated protein kinases, a
      pathway that is considered important for the mitotic effects of VEGF. Thus,
      blockade of PI3K by luteolin was responsible for the inhibitory effects of the
      compound on VEGF-induced survival and proliferation of HUVECs. The antisurvival
      effects of luteolin were mediated via blockage of PI3K/Akt-dependent pathways,
      whereas inhibition of the PI3K/p70 S6K pathway mediated the antimitotic effects
      of the compound.

PMID- 15520199
TI  - The synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid induces
      caspase-dependent and -independent apoptosis in acute myelogenous leukemia.
AB  - In acute myeloid leukemia (AML), resistance to chemotherapy is associated with
      defects in both the extrinsic and intrinsic pathways of apoptosis. Novel agents
      that activate endogenous apoptosis-inducing mechanisms directly may be
      potentially useful to overcome chemoresistance in AML. We examined the mechanisms
      of apoptosis induction by the novel synthetic triterpenoid 2-cyano-3,12
      dioxooleana-1,9-dien-28-oic acid (CDDO) in AML cells. CDDO-induced apoptosis was
      associated with the loss of mitochondrial inner transmembrane potential, caspases
      activation, the translocation of apoptosis-inducing factor to the nucleus, and
      DNA fragmentation in AML cells. Apoptosis was equally evident in cells deficient
      in caspase-9 or caspase-8 after exposure to CDDO, suggesting caspase-independent
      cell death. The use of small interfering RNA to reduce the expression of
      apoptosis-inducing factor partially inhibited CDDO-induced apoptosis in AML
      cells. Cells overexpressing Bcl-2 were markedly resistant to CDDO-induced
      apoptosis. Moreover, CDDO promoted the release of cytochrome c from isolated
      mitochondria, suggesting that CDDO targets the mitochondria directly to trigger
      the intrinsic pathway of cell death in intact cells. Together, these results
      suggest that CDDO functions by activating the intrinsic pathway of apoptosis and
      initiates caspase-dependent and independent cell death. The direct modulation of
      mitochondrial-mediated, caspase-independent apoptosis by CDDO may be advantageous
      for overcoming chemoresistance in AML.

PMID- 15520201
TI  - Breast cancer cells can evade apoptosis-mediated selective killing by a novel
      small molecule inhibitor of Bcl-2.
AB  - Proteins of the Bcl-2 family are key regulators of caspase activation and
      apoptosis. Some members of this family, notably Bcl-2 and Bcl-x(L), are
      overexpressed in cancer cells, which have been associated with chemoresistance.
      We have designed and synthesized a small molecule inhibitor of Bcl-2, named
      YC137, and studied its role in cancer cells. In vitro studies showed that YC137
      inhibits the binding of the Bid BH3 peptide to Bcl-2, thus disrupting an
      interaction essential for the antiapoptotic activity of Bcl-2. This inhibitor
      induces apoptosis of hematopoietic progenitors overexpressing Bcl-2 but not Bcl
      x(L) and breast cancer cells that express high levels of Bcl-2. On the contrary,
      a variety of normal primary cells, including CD34(+) progenitors, myoblasts, and
      peripheral blood mononuclear cells, do not respond to the inhibitor. A breast
      cancer cell line resistant to YC137 was generated. Analysis of resistant cells
      revealed a reduced expression of Bcl-2, which correlated with low activation of
      signal transducer and activator of transcription-3 (Stat3) and reduced expression
      of the human epidermal growth factor receptor-2 (HER2). Of note, YC137-resistant
      cells were more sensitive to apoptosis induced by chemotherapy. Because HER2 has
      not been linked previously to the Stat3-Bcl-2 transcriptional pathway, we
      additionally confirmed that specific blockade of HER2 in breast cancer cells
      resulted in down-regulation of Stat3 activity and reduced levels of Bcl-2.
      Consistently, HER2 blockade led to YC137 resistance. These data provide evidence
      for the selective killing of tumor cells by YC137 and represent the first example
      of in vitro selection of cancer cells refractory to a Bcl-2 inhibitor.

PMID- 15520202
TI  - SD-208, a novel transforming growth factor beta receptor I kinase inhibitor,
      inhibits growth and invasiveness and enhances immunogenicity of murine and human
      glioma cells in vitro and in vivo.
AB  - The cytokine transforming growth factor (TGF)-beta, by virtue of its
      immunosuppressive and promigratory properties, has become a major target for the
      experimental treatment of human malignant gliomas. Here we characterize the
      effects of a novel TGF-beta receptor (TGF-betaR) I kinase inhibitor, SD-208, on
      the growth and immunogenicity of murine SMA-560 and human LN-308 glioma cells in
      vitro and the growth of and immune response to intracranial SMA-560 gliomas in
      syngeneic VM/Dk mice in vivo. SD-208 inhibits the growth inhibition of TGF-beta
      sensitive CCL64 cells mediated by recombinant TGF-beta1 or TGF-beta2 or of TGF
      beta-containing glioma cell supernatant at an EC(50) of 0.1 mumol/L. SD-208
      blocks autocrine and paracrine TGF-beta signaling in glioma cells as detected by
      the phosphorylation of Smad2 or TGF-beta reporter assays and strongly inhibits
      constitutive and TGF-beta-evoked migration and invasion, but not viability or
      proliferation. Peripheral blood lymphocytes or purified T cells, cocultured with
      TGF-beta-releasing LN-308 glioma cells in the presence of SD-208, exhibit
      enhanced lytic activity against LN-308 targets. The release of interferon gamma
      and tumor necrosis factor alpha by these immune effector cells is enhanced by SD
      208, whereas the release of interleukin 10 is reduced. SD-208 restores the lytic
      activity of polyclonal natural killer cells against glioma cells in the presence
      of recombinant TGF-beta or of TGF-beta-containing glioma cell supernatant. The
      oral bioavailability of SD-208 was verified by demonstrating the inhibition of
      TGF-beta-induced Smad phosphorylation in spleen and brain. Systemic SD-208
      treatment initiated 3 days after the implantation of SMA-560 cells into the
      brains of syngeneic VM/Dk mice prolongs their median survival from 18.6 to 25.1
      days. Histologic analysis revealed no difference in blood vessel formation,
      proliferation, or apoptosis. However, animals responding to SD-208 showed an
      increased tumor infiltration by natural killer cells, CD8 T cells, and
      macrophages. These data define TGF-beta receptor I kinase inhibitors such as SD
      208 as promising novel agents for the treatment of human malignant glioma and
      other conditions associated with pathological TGF-beta activity.

PMID- 15520203
TI  - RNA interference reveals that ligand-independent met activity is required for
      tumor cell signaling and survival.
AB  - Hepatocyte growth factor/scatter factor-Met signaling has been implicated in
      tumor growth, invasion, and metastasis. Suppression of this signaling pathway by
      targeting the Met protein tyrosine kinase may be an ideal strategy for
      suppressing malignant tumor growth. Using RNA interference technology and
      adenovirus vectors carrying small-interfering RNA constructs (Ad Met small
      interfering RNA) directed against mouse, canine, and human Met, we can knock down
      c-met mRNA. We show a dramatic dependence on Met in both ligand-dependent and
      ligand-independent mouse, canine, and human tumor cell lines. Mouse mammary tumor
      (DA3) cells and Met-transformed NIH3T3 (M114) cells, as well as both human and
      canine prostate cancer (PC-3 and TR6LM, human sarcoma (SK-LMS-1), glioblastoma
      (DBTRG), and gastric cancer (MKN45) cells, all display a dramatic reduction of
      Met expression after infection with Ad Met small-interfering RNA. In these cells,
      we observe suppression of tumor cell growth and viability in vitro as well as
      inhibition of hepatocyte growth factor/scatter factor-mediated scattering and
      invasion in vitro, whether Met activation was ligand dependent or not.
      Importantly, Ad Met small-interfering RNA led to apoptotic cell death in many of
      the tumor cell lines, especially DA3 and MKN45, but did not adversely affect MDCK
      canine kidney cells. Met small-interfering RNA also abrogated downstream Met
      signaling to molecules such as Akt and p44/42 mitogen-activated protein kinase.
      We further show that intratumoral infection with c-met small-interfering RNA
      adenovirus results in a substantial reduction in tumor growth. Thus, Met small
      interfering RNA adenoviruses are reliable tools for studying Met function and
      raise the possibility of their application for cancer therapy.

PMID- 15520204
TI  - Aerosol delivery of glucosylated polyethylenimine/phosphatase and tensin
      homologue deleted on chromosome 10 complex suppresses Akt downstream pathways in
      the lung of K-ras null mice.
AB  - Difficulties in achieving long-term survival of lung cancer patients treated with
      conventional therapies suggest that novel approaches are required. Although
      several genes have been investigated for antitumor activities using gene
      delivery, problems surrounding the methods used such as efficiency, specificity,
      and toxicity hinder its application as an effective therapy. This has lead to the
      re-emergence of aerosol gene delivery as a noninvasive approach to lung cancer
      therapy. In this study, glucosylated conjugated polyethylenimine (glucosylated
      PEI) was used as carrier. After confirming the efficiency of glucosylated PEI
      carriers in lungs, the potential effects of the phosphatase and tensin homologue
      deleted on chromosome 10 (PTEN) tumor suppressor gene on Akt downstream pathways
      were investigated. Aerosol containing glucosylated PEI and recombinant plasmid
      pcDNA3.0-PTEN complex was delivered into K-ras null lung cancer model mice
      through a nose-only inhalation system. Investigation of proteins in the
      phosphatidylinositol 3'-kinase/Akt signaling pathway in PTEN-delivered mouse lung
      revealed that the PTEN protein was highly expressed, whereas the protein levels
      of PDK1, total Akt1, phospho-(Thr-308)-Akt, phospho-(Ser-2448)-mTOR, p70S6K, and
      4E-BP1 were decreased to varying degrees. Additionally, the kinase activities of
      both Akt and mTOR were suppressed. Finally, apoptosis was detected in PTEN
      delivered mouse lung by terminal deoxynucleotidyltransferase-mediated nick end
      labeling assay, suggesting that our aerosol PTEN delivery is capable of
      functionally altering cell phenotype in vivo. In summary, Western blot analysis,
      kinase assays, immunohistochemistry, and terminal deoxynucleotidyltransferase
      mediated nick end labeling assays suggest that our aerosol gene delivery
      technique is compatible with in vivo gene delivery and can be applied as a
      noninvasive gene therapy.

PMID- 15520205
TI  - Tumor cell and endothelial cell therapy of oral cancer by dual tyrosine kinase
      receptor blockade.
AB  - Expression of the epidermal growth factor (EGF) and activation of its receptor
      (EGFR), a tyrosine kinase, are associated with progressive growth of head and
      neck cancer. Expression of the vascular endothelial growth factor (VEGF) is
      associated with angiogenesis and progressive growth of tumor. The tyrosine kinase
      inhibitor NVP-AEE788 (AEE788) blocks the EGF and VEGF signaling pathways. We
      examined the effects of AEE788 administered alone, or with paclitaxel (Taxol), on
      the progression of human head and neck cancer implanted orthotopically into nude
      mice. Cells of two different human oral cancer lines, JMAR and MDA1986, were
      injected into the tongues of nude mice. Mice with established tumors were
      randomized to receive three times per week oral AEE788, once weekly injected
      paclitaxel, AEE788 plus paclitaxel, or placebo. Oral tumors were resected at
      necropsy. Kinase activity, cell proliferation, apoptosis, and mean vessel density
      were determined by immunohistochemical immunofluorescent staining. AEE788
      inhibited cell growth, induced apoptosis, and reduced the phosphorylation of
      EGFR, VEGFR-2, AKT, and mitogen-activated protein kinase in both cell lines. Mice
      treated with AEE788 and AEE788 plus paclitaxel had decreased microvessel density,
      decreased proliferative index, and increased apoptosis. Hence, AEE788 inhibited
      tumor vascularization and growth and prolonged survival. Inhibition of EGFR and
      VEGFR phosphorylation by AEE788 effectively inhibits cellular proliferation of
      squamous cell carcinoma of the head and neck, induces apoptosis of tumor
      endothelial cells and tumor cells, and is well tolerated in mice. These data
      recommend the consideration of patients with head and neck cancer for inclusion
      in clinical trials of AEE788.

PMID- 15520206
TI  - Sublethal irradiation of human tumor cells modulates phenotype resulting in
      enhanced killing by cytotoxic T lymphocytes.
AB  - Local radiation of tumor masses is an established modality for the therapy of a
      range of human tumors. It has recently been recognized that doses of radiation,
      lower than or equal to those that cause direct cytolysis, may alter the phenotype
      of target tissue by up-regulating gene products that may make tumor cells more
      susceptible to T-cell-mediated immune attack. Previously, we demonstrated that
      radiation increased Fas (CD95) gene expression in carcinoembryonic antigen (CEA)
      expressing murine tumor cells, which consequently enhanced their susceptibility
      to CEA-specific CTL-mediated killing. The present study was designed to determine
      whether these phenomena also occur with human tumor cells. Here, 23 human
      carcinoma cell lines (12 colon, 7 lung, and 4 prostate) were examined for their
      response to nonlytic doses of radiation (10 or 20 Gy). Seventy-two hours
      postirradiation, changes in surface expression of Fas (CD95), as well as
      expression of other surface molecules involved in T-cell-mediated immune attack
      such as intercellular adhesion molecule 1, mucin-1, CEA, and MHC class I, were
      examined. Twenty-one of the 23 (91%) cell lines up-regulated one or more of these
      surface molecules postirradiation. Furthermore, five of five irradiated
      CEA(+)/A2(+) colon tumor cells lines demonstrated significantly enhanced killing
      by CEA-specific HLA-A2-restricted CD8(+) CTLs compared with nonirradiated
      counterparts. We then used microarray analysis to broaden the scope of observed
      changes in gene expression after radiation and found that many additional genes
      had been modulated. These up-regulated gene products may additionally enhance the
      tumor cells' susceptibility to T-cell-mediated immune attack or serve as
      additional targets for immunotherapy. Overall, the results of this study suggest
      that nonlethal doses of radiation can be used to make human tumors more amenable
      to immune system recognition and attack and form the rational basis for the
      combinatorial use of cancer vaccines and local tumor irradiation.

PMID- 15520207
TI  - A prostate-specific membrane antigen-targeted monoclonal antibody
      chemotherapeutic conjugate designed for the treatment of prostate cancer.
AB  - MLN2704 is an antibody-chemotherapeutic conjugate designed to target prostate
      specific membrane antigen (PSMA). PSMA is a transmembrane receptor whose
      expression is largely restricted to prostatic epithelium and prostate cancer
      cells with its expression level increasing during the progression of malignancy.
      MLN2704 consists of a de-immunized, monoclonal antibody that is specific for PSMA
      conjugated to drug maytansinoid 1 (DM1), a microtubule-depolymerizing compound.
      After antibody binding to PSMA and the subsequent cellular internalization of
      this complex, DM1 is released leading to cell death. MLN2704 has an approximate
      half-life of 39 hours in scid mice bearing CWR22 tumor tissue, and the antibody
      effectively penetrates xenograft tumor tissue. Optimization of dosage and
      schedule of MLN2704 administration defined interdependency between these
      conditions that maximized efficacy with no apparent toxicity. Tumor growth delays
      of approximately 100 days could be achieved on the optimized schedule of one dose
      of 60 mg/kg MLN2704 every 14 days for five doses (q14dx5). The unconjugated
      antibody (MLN591) demonstrated essentially no antitumor activity and DM1 alone or
      a non-PSMA targeted antibody-DM1 conjugate was only weakly active. Furthermore,
      we show that MLN2704 is active in a novel model of osteoblastic prostate cancer
      metastasis.

PMID- 15520208
TI  - A novel peptide specifically binding to nasopharyngeal carcinoma for targeted
      drug delivery.
AB  - Nasopharyngeal carcinoma (NPC) is a common cancer among Chinese living in
      southern China, Taiwan, and Singapore. The 5-year survival rate in the early
      stage of NPC has been reported as high as 90 to 95% with the use of radiotherapy,
      but in the advanced cases, even with the use of both chemotherapy and
      radiotherapy, the survival rate is still <50%. To improve the survival rate, we
      identify a 12-mer peptide (L-peptide) specifically binding to NPC cells with a
      phage displayed random peptide library. The L-phage and synthetic L-peptide bound
      to the tumor cell surfaces of most NPC cell lines and biopsy specimens, but not
      normal nasal mucosal cells, and the L-peptide-linked liposomes containing
      fluorescent substance (L-peptide-Lipo-HPTS) were capable of binding to and
      translocating across plasma membranes. L-Peptide-linked liposomes that carried
      doxorubicin (L-peptide-Lipo-Dox) caused marked cytotoxicity in NPC cells. In SCID
      mice bearing NPC xenografts, the L-phages specifically bound to the tumor mass,
      an effect that was inhibited by competition with synthetic L-peptide. In
      addition, the L-peptide-Lipo-Dox suppressed tumor growth better than Lipo-Dox.
      These results indicate that the novel L-peptide specifically binds NPC cells and
      is a good candidate for targeted drug delivery to NPC solid tumors.

PMID- 15520209
TI  - In vivo near-infrared fluorescence imaging of integrin alphavbeta3 in brain tumor
      xenografts.
AB  - Noninvasive visualization of cell adhesion molecule alpha(v)beta(3) integrin
      expression in vivo has been well studied by using the radionuclide imaging
      modalities in various preclinical tumor models. A literature survey indicated no
      previous use of cyanine dyes as contrast agents for in vivo optical detection of
      tumor integrin. Herein, we report the integrin receptor specificity of novel
      peptide-dye conjugate arginine-glycine-aspartic acid (RGD)-Cy5.5 as a contrast
      agent in vitro, in vivo, and ex vivo. The RGD-Cy5.5 exhibited intermediate
      affinity for alpha(v)beta(3) integrin (IC(50) = 58.1 +/- 5.6 nmol/L). The
      conjugate led to elevated cell-associated fluorescence on integrin-expressing
      tumor cells and endothelial cells and produced minimal cell fluorescence when
      coincubated with c(RGDyK). In vivo imaging with a prototype three-dimensional
      small-animal imaging system visualized subcutaneous U87MG glioblastoma xenograft
      with a broad range of concentrations of fluorescent probe administered via the
      tail vein. The intermediate dose (0.5 nmol) produces better tumor contrast than
      high dose (3 nmol) and low dose (0.1 nmol) during 30 minutes to 24 hours
      postinjection, because of partial self-inhibition of receptor-specific tumor
      uptake at high dose and the presence of significant amount of background
      fluorescence at low dose, respectively. The tumor contrast was also dependent on
      the mouse viewing angles. Tumor uptake of RGD-Cy5.5 was blocked by unlabeled
      c(RGDyK). This study suggests that the combination of the specificity of RGD
      peptide/integrin interaction with near-infrared fluorescence detection may be
      applied to noninvasive imaging of integrin expression and monitoring anti
      integrin treatment efficacy providing near real-time measurements.

PMID- 15520210
TI  - Nitric oxide and ionizing radiation synergistically promote apoptosis and growth
      inhibition of cancer by activating p53.
AB  - Nitric oxide (NO) is a potent tumor radiosensitizer; however, its clinical use is
      limited by systemic side effects. We have demonstrated previously that gene
      transfer of the human inducible NO synthase (iNOS) gene into tumor cells and
      tumors induces high-output NO production that significantly enhances tumor
      radioresponsiveness, with no observed side effects. Notably, iNOS gene transfer
      enhances tumor radioresponsiveness via apoptotic cell death. Because NO and
      ionizing radiation are both known to promote p53-dependent apoptosis, we
      hypothesized that p53 activation might be a primary mechanism for the synergy of
      these two genotoxic stresses. We report that NO and ionizing radiation
      synergistically activate p53 in colorectal cancers grown in athymic mice by
      augmenting phosphorylation of p53 at serine 15. The effect of NO and ionizing
      radiation on tumor cell apoptosis and tumor radioresponsiveness is significantly
      reduced in p53 knockout isogenic cancer cell lines. Furthermore, the transfer of
      both p53 and iNOS genes into tumor cells lacking functional p53 enhanced their
      radioresponsiveness more than transfer of either gene alone.

PMID- 15520211
TI  - Vaccination by genetically modified dendritic cells expressing a truncated neu
      oncogene prevents development of breast cancer in transgenic mice.
AB  - Dendritic cells (DCs) are powerful antigen-presenting cells that process antigens
      and present peptide epitopes in the context of the major histocompatibility
      complex molecules to generate immune responses. DCs are being studied as
      potential anticancer vaccines because of their ability to present antigens to
      naive T cells and to stimulate the expansion of antigen-specific T-cell
      populations. We investigated an antitumor vaccination using DCs modified by
      transfer of a nonsignaling neu oncogene, a homologue of human HER-2/neu, in a
      transgenic model of breast cancer. BALB-neuT mice develop breast cancers as a
      consequence of mammary gland-specific expression of an activated neu oncogene. We
      vaccinated BALB-neuT mice with bone marrow-derived DCs transduced with Ad.Neu, a
      recombinant adenovirus expressing a truncated neu oncoprotein. The vaccine
      stimulated the production of specific anti-neu antibodies, enhanced interferon
      gamma expression by T cells, and prevented or delayed the onset of mammary
      carcinomas in the mice. Over 65% of vaccinated mice remained tumor free at 28
      weeks of age, whereas all of the mice in the control groups developed tumors.
      When challenged with a neu-expressing breast cancer cell line, vaccinated tumor
      free animals had delayed tumor growth compared with controls. The antitumor
      effect of the vaccine was specific for expression of neu. Studies showed that
      CD4+ T cells were required in order to generate antitumor immunity. Importantly,
      the effectiveness of the vaccine was not diminished by preexisting immunity to
      adenovirus, whereas the protection afforded by vaccination that used direct
      injection of Ad.Neu was markedly reduced in mice with anti-adenovirus antibody
      titers. DCs modified by recombinant adenoviruses expressing tumor-associated
      antigens may provide an effective antitumor vaccination strategy.

PMID- 15520212
TI  - DNA polymerase zeta regulates cisplatin cytotoxicity, mutagenicity, and the rate
      of development of cisplatin resistance.
AB  - DNA polymerase zeta participates in translesional bypass replication. Here we
      show that reduced expression of the catalytic subunit hREV3 renders human
      fibroblasts more sensitive to the cytotoxic effect of cisplatin, reduces their
      sensitivity to the ability of cisplatin exposure to generate drug resistant
      variants in the surviving population, and reduces the rate of emergence of
      resistance to cisplatin at the population level. Reduction of REV3 mRNA did not
      alter the rate of cisplatin adduct removal but did impair both spontaneous and
      cisplatin-induced extrachromosomal homologous recombination and attenuated bypass
      replication as reflected by reduced ability to express luciferase from a
      platinated plasmid. Cisplatin induced a concentration- and time-dependent
      increase in hREV3 mRNA. The results indicate that, following formation of
      cisplatin adducts in DNA, REV3 mRNA levels increase, and polymerase zeta
      functions to promote both cell survival and the generation of drug-resistant
      variants in the surviving population. We conclude that when cisplatin adducts are
      present in the DNA, polymerase zeta is an important contributor to cisplatin
      induced genomic instability and the subsequent emergence of resistance to this
      chemotherapeutic agent.

PMID- 15520213
TI  - Casein kinase I attenuates tumor necrosis factor-related apoptosis-inducing
      ligand-induced apoptosis by regulating the recruitment of fas-associated death
      domain and procaspase-8 to the death-inducing signaling complex.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis
      in a wide variety of malignant cell lines, in contrast to normal cells, but with
      considerable heterogeneity in response. Death receptor-mediated apoptosis may be
      attenuated by a variety of different mechanisms, including phosphorylation-based
      signaling pathways. We have demonstrated that casein kinase I can attenuate TRAIL
      induced apoptosis in human cell lines derived from colon adenocarcinoma (HT29 and
      HCT8) and pediatric rhabdomyosarcoma (JR1). Inhibition of casein kinase I (CKI)
      phosphorylation events in HT29, HCT8, and JR1 cells by CKI-7 dramatically
      increased apoptosis after exposure to TRAIL, in the absence of apoptosis induced
      by TRAIL treatment alone. CKI inhibition enhanced the recruitment of Fas
      associated death domain and procaspase-8 to the death-inducing signaling complex
      after TRAIL treatment and enhanced cleavage of procaspase-8 at the death-inducing
      signaling complex. In HT29 cells studied further, rapid cleavage of caspase-8,
      caspase-3, Bid, and the caspase substrate poly(ADP-ribose) polymerase occurred
      when CKI-7 and TRAIL were combined. Overexpression of Bcl-2, Bcl-xL, or mutant DN
      Fas-associated death domain protected HT29 cells from TRAIL-induced apoptosis in
      the presence of the CKI inhibitor. In addition, TRAIL combined with CKI-7
      promoted the release of cytochrome c, Smac/DIABLO, HtrA2/Omi, and AIF from the
      mitochondria and down-regulated the expression of XIAP and c-IAP1. Small hairpin
      RNAs directed against CKI revealed that the CKIalpha isoform contributed
      significantly to the inhibition of TRAIL-induced apoptosis. These findings
      suggest that CKIalpha plays an antiapoptotic role through the generation of
      phosphorylated sites at the level of the death-inducing signaling complex,
      thereby conferring resistance to caspase cleavage mediated by TRAIL.

PMID- 15520214
TI  - Long-term radioiodine retention and regression of liver cancer after sodium
      iodide symporter gene transfer in wistar rats.
AB  - Radioiodine therapy of nonthyroid cancers after sodium iodide symporter (NIS)
      gene delivery has been proposed as a potential application of gene therapy.
      However, it seems to be precluded by the rapid efflux of taken up iodine from
      most transduced xenografted tumors. We present an in vivo kinetic study of NIS
      related hepatic iodine uptake in an aggressive model of hepatocarcinoma induced
      by diethylnitrosamine in immunocompetent Wistar rats. We followed the whole-body
      iodine distribution by repeated imaging of live animals. We constructed a rat NIS
      (rNIS) adenoviral vector, Ad-CMV-rNIS, using the cytomegalovirus (CMV) as a
      promoter. Injected in the portal vein in 5 healthy and 25 hepatocarcinoma-bearing
      rats and liver tumors in 9 hepatocarcinoma-bearing rats, Ad-CMV-rNIS drove
      expression of a functional NIS protein by hepatocytes and allowed marked (from 20
      to 30% of the injected dose) and sustained (>11 days) iodine uptake. This
      contrasts with the massive iodine efflux found in vitro in human hepatic tumor
      cell lines. In vivo specific inhibition of NIS by sodium perchlorate led to a
      rapid iodine efflux from the liver, indicating that the sustained uptake was not
      attributable to an active retention mechanism but to permanent recycling of the
      effluent radioiodine via the high hepatic blood flow. Radioiodine therapy after
      Ad-CMV-rNIS administration achieved a strong inhibition of tumor growth, the
      complete regression of small nodules, and prolonged survival of hepatocarcinoma
      bearing rats. This demonstrates for the first time the efficacy of NIS-based
      radiotherapy in a relevant preclinical model of nonthyroid human carcinogenesis.

PMID- 15520215
TI  - Induction of unresponsiveness limits tumor protection by adoptively transferred
      MDM2-specific cytotoxic T lymphocytes.
AB  - There is evidence showing that high avidity CTLs can be more effective than low
      avidity CTLs for adoptive tumor immunotherapy. Because many T cell-recognized
      tumor antigens are nonmutated self-proteins, tolerance mechanisms are likely to
      render high avidity T cells unresponsive or cause T cell elimination by clonal
      deletion. We recently used the allo-restricted strategy to circumvent immunologic
      tolerance to a ubiquitously expressed tumor-associated protein, MDM2, and raised
      high avidity CTLs in humans and in mice. In this study, we investigated whether
      high avidity MDM2-specific CTLs can mediate tumor protection without causing
      damage to normal tissues in mice. Although the CTLs prolonged survival of tumor
      bearing mice without causing damage to normal tissues, tumor protection was
      incomplete. We show that tumor growth occurred despite the continued presence of
      MDM2-specific CTLs and the continued susceptibility of tumor cells to CTL
      killing. However, analysis of the CTLs revealed that they had been rendered
      unresponsive in vivo because they did not produce interferon gamma in response to
      antigen-specific stimulation. These experiments suggest that induction of
      unresponsiveness may be an important mechanism limiting the efficacy of adoptive
      CTL therapy.

PMID- 15520216
TI  - Antitumor vaccination in patients with head and neck squamous cell carcinomas
      with autologous virus-modified tumor cells.
AB  - Prognosis of patients with advanced head and neck squamous cell carcinomas
      (HNSCC) is still poor. Therefore, we analyzed whether antitumor vaccination with
      a virus-modified autologous tumor cell vaccine is feasible and safe in HNSCC
      patients. Furthermore, we determined the influence on disease-free survival and
      overall survival and the vaccination-induced antitumor reactivity. In a
      nonrandomized pilot study, 20 patients were vaccinated postoperatively. Vaccine
      was prepared from the tumor cell cultures of patients by infection of the cells
      with Newcastle Disease Virus, followed by gamma-irradiation, and vaccine was
      applied up to five times. Antitumor immune reactivity was determined in the skin
      by delayed type hypersensitivity skin reaction and in the blood by enzyme-linked
      immunospot assay. Establishment of tumor cell cultures was successful in about
      80% of the cases. After vaccination, we observed no severe side effects.
      Percentages of survival of vaccinated patients with stage III and stage IV tumors
      (n = 18) were 61% at 5 years. Immune monitoring revealed significant increases of
      antitumor delayed type hypersensitivity reactivity especially in disease-free
      patients, and in a significant proportion of vaccinated patients the presence of
      tumor-reactive T-cells in the peripheral blood even 5 to 7 years after the last
      vaccination. Postoperative vaccination with virus-modified autologous tumor cells
      seems to be feasible and safe and may improve the prognosis of HNSCC patients
      with advanced tumors. This could be supported by antitumor immune responses that
      we observed especially in long-term surviving patients.

PMID- 15520217
TI  - Failed adoptive immunotherapy with tumor-specific T cells: reversal with low-dose
      interleukin 15 but not low-dose interleukin 2.
AB  - Adoptive immunotherapy with tumor-specific T cells has emerged as a valid
      approach for prevention or treatment of diseases, such as melanoma and EBV
      associated lymphoma. As interleukin (IL) 15 promotes survival of CD8(+) memory
      CTLs, we hypothesized that it could be used to enhance antitumor immunity in vivo
      through the maintenance of adoptively transferred memory CTL. To test this, we
      treated mice bearing P1A(+) tumors with adoptively transferred T cells possessing
      a transgenic Valpha8(+) T-cell receptor specific for the P1A tumor antigen
      (called P1CTL). Mice were then randomized to receive daily low-dose IL-15 (0.5
      microg/day) or PBS. Mice receiving the transgenic P1CTL and IL-15 experienced a
      significantly delayed tumor relapse or complete tumor regression (P < 0.002
      compared with PBS), with a striking persistence of the CD8(+) Valpha8(+) P1CTL
      compared with mice receiving the CD8(+) Valpha8(+) P1CTL and PBS vehicle (26.3
      versus 5.1% P < 10(-5)). Animals exhibiting complete tumor regression had a
      significant population of CD8(+) Valpha8(+) P1CTL (46%) that persisted with IL-15
      treatment until 140 days after adoptive transfer and successfully defended them
      against tumor rechallenge without IL-15. Low-dose IL-2 afforded no protection
      over vehicle and resulted in lower percentages of T cells with an activated
      memory phenotype, lower Bcl-2 expression, and lower ex vivo antitumor
      cytotoxicity compared with mice treated with IL-15. Collectively, the data
      support the notion that exogenous low-dose IL-15 therapy can enhance and even
      reverse the limited efficacy of adoptively transferred tumor-specific T-cell
      therapy and may do so in a fashion that is superior and distinct from exogenous
      IL-2 therapy.

PMID- 15520218
TI  - Therapeutic effectiveness of recombinant cancer vaccines is associated with a
      prevalent T-cell receptor alpha usage by melanoma-specific CD8+ T lymphocytes.
AB  - Definition of immune variables that correlate with the antitumor activity of
      cancer vaccines is critical for monitoring immunotherapy protocols. To define
      surrogate end points predictive of the therapeutic efficacy of recombinant
      vaccines based on melanoma antigen tyrosinase-related protein (TRP)-2, we
      evaluated several properties of antigen-specific CD8(+) T lymphocytes in single
      mice undergoing either prophylactic or therapeutic immunization. Predictive
      markers for the efficacy of genetic vaccination were identified in the
      prophylactic model used. Interestingly, the number of tetramer(+) CD8(+) T
      lymphocytes expanded in vitro after a single cycle of stimulation with the
      immunodominant TRP-2 peptide was of the highest predictive value. In the
      therapeutic model, no variable examined at a single mouse level predicted the
      long-term therapeutic effect. Mice that survived did not show the highest
      expansion of antigen-specific lymphocytes or the more functionally active
      effectors, ex vivo or after in vitro culture with the peptide antigen. Successful
      therapy correlated strictly with the skewing of the T-cell receptor repertoire of
      tetramer-sorted, TRP-2-specific CD8(+) T lymphocytes, which showed a preferential
      alpha chain usage with a common CDR3 region.

PMID- 15520219
TI  - A unique mucin immunoenhancing peptide with antitumor properties.
AB  - Implantation of DA-3 mammary tumor cells into BALB/c mice results in tumor
      growth, metastatic lesions, and death. These cells were transfected with genes
      encoding for either the transmembrane (DA-3/TM) or secreted (DA-3/sec) form of
      human mucin 1 (MUC1). Although the gene for the secreted form lacks the
      transmembrane and cytoplasmic domains, the 5' sequences of these mucins are
      identical; however, the gene for the secreted mucin isoform ends with a sequence
      encoding for a unique 11 amino acid peptide. The DA-3/TM or DA-3 cells
      transfected with the neomycin vector only (DA-3/neo) have the same in vivo growth
      characteristics as the parent cell line. In contrast, DA-3/sec cells fail to grow
      when implanted in immunocompetent BALB/c animals. DA-3/sec cells implanted in
      nude mice resulted in tumor development verifying the tumorigenic potential of
      these cells. Pre-exposure of BALB/c mice to DA-3/sec cells afforded protection
      against challenge with DA-3/TM or DA-3/neo mammary tumors and the unrelated
      tumors K7, an osteosarcoma, and RENCA, a renal cell carcinoma. Partial protection
      against subsequent tumor challenges was also achieved by substituting the 11
      amino acid peptide found only in the secreted MUC1 isoform, for the live DA-3/sec
      cells. Notably, the efficacy of this peptide is not strain restricted because it
      also retarded the growth of Lewis lung carcinoma cells in C57 BL/6 mice. These
      findings reveal that a unique peptide present in the secreted MUC1 has
      immunoenhancing properties and may be a potential agent for use in immunotherapy.

PMID- 15520220
TI  - Cargo from tumor-expressed albumin inhibits T-cell activation and responses.
AB  - In this study, we show that rodent albumin is expressed by and cell surface
      localized on at least some murine tumor cells. We have been able to purify this
      tumor-expressed albumin from in vivo grown tumor masses. The tumor-expressed
      albumin, unlike normal serum albumin purified from blood, is capable of
      inhibiting T-cell activation, proliferation, and function in both in vitro and in
      vivo settings. Tumor-expressed albumin does not appear to affect antigen
      processing or presentation by professional antigen-presenting cells. The activity
      appears to lie in relatively small, lipid-like moieties that are presumably cargo
      for tumor-expressed albumin, and that activity can be removed from the albumin by
      lipid removal or treatment with lipase. Thus, we herein report of a novel form of
      tumor-induced immune suppression attributable to lipid-like entities, cloaked by
      albumin produced by tumors.

PMID- 15520221
TI  - Insulin receptor, insulin receptor substrate-1, Raf-1, and Mek-1 during hormonal
      hepatocarcinogenesis by intrahepatic pancreatic islet transplantation in diabetic
      rats.
AB  - Low-number transplantation of pancreatic islets into the livers of diabetic rats
      leads to transformation of the downstream liver acini into clear-cell foci of
      altered hepatocytes (FAHs). These FAHs correspond to the glycogen-storing (clear
      cell) phenotype of hepatocellular preneoplasias and develop into hepatocellular
      adenomas (HCAs) and hepatocellular carcinomas (HCCs) within 6 to 24 months. In
      addition, they show metabolic alterations that resemble well-known insulin
      effects, most likely constituting the result of the local hyperinsulinemia. Thus,
      we investigated FAHs, HCAs, and HCCs for altered expression of insulin receptor,
      insulin receptor substrate-1 (IRS-1), Raf-1 and Mek-1. Light and electron
      microscopic immunohistochemistry revealed a translocation of insulin receptor
      from the plasma membrane (normal tissue) into the cytoplasm in clear-cell FAHs
      and an increase in insulin receptor expression in HCAs and HCCs. FAHs also showed
      an increase in IRS-1 gene expression, investigated by in situ hybridization and
      quantitative reverse transcription-PCR. IRS-1, Raf-1, and Mek-1 proteins were
      strongly overexpressed in FAHs and tumors, as compared with the unaltered liver
      tissue. These overexpressions were closely linked to the clear-cell phenotype of
      preneoplastic and neoplastic hepatocytes, because basophilic FAHs (later stages)
      and basophilic tumors showed no overexpressions. In this endocrine model of
      hepatocarcinogenesis, severe alterations of insulin signaling were induced by the
      pathological local action of islet hormones in the livers and may substantially
      contribute to the carcinogenic process.

PMID- 15520222
TI  - Absence or low expression of fas-associated protein with death domain in acute
      myeloid leukemia cells predicts resistance to chemotherapy and poor outcome.
AB  - In acute myeloid leukemia (AML), coexpression of death receptors and ligands of
      the tumor necrosis factor (TNF) receptor/TNF-alpha superfamily on leukemic cells
      after chemotherapy is not always accompanied by apoptosis, suggesting that the
      apoptotic death receptor signaling pathway is disrupted. Because Fas-associated
      protein with death domain (FADD) is the main adaptor for transmitting the Fas,
      TNF-related apoptosis-inducing ligand receptors, and TNF receptor 1 death signal,
      expression of FADD was analyzed by Western blot and immunocytochemistry in
      leukemic cells of 70 de novo AML patients treated with the European Organization
      of Research and Treatment of Cancer AML-10 randomized trial before initiation of
      induction chemotherapy. Thirty seven percent of patients (17 of 46) with FADD
      negative/low (FADD(-/low)) leukemic cells had a primary refractory disease
      compared with 12% of FADD(+) patients (3 of 24; P = 0.05). FADD(-/low) expression
      was significantly associated with a worse event-free survival [EFS (P = 0.04)]
      and overall survival (P = 0.04). In multivariate analysis, FADD(-/low) protein
      expression was independently associated with a poor EFS and overall survival (P =
      0.002 and P = 0.026, respectively). Importantly, FADD(-/low) protein expression
      predicted poor EFS even in patients with standard- or good-risk AML (P = 0.009).
      Thus, we identified low or absent expression of the FADD protein in leukemic
      cells at diagnosis as a poor independent prognostic factor that can predict worse
      clinical outcome even for patients with standard- or good-risk AML.

PMID- 15520223
TI  - Microarray analyses uncover UBE1L as a candidate target gene for lung cancer
      chemoprevention.
AB  - Retinoids, natural and synthetic derivatives of vitamin A, are active in cancer
      therapy and chemoprevention. We reported previously that all-trans-retinoic acid
      (RA) treatment prevented carcinogen-induced transformation of immortalized human
      bronchial epithelial (HBE) cells. To identify cancer chemopreventive mechanisms,
      immortalized (BEAS-2B), carcinogen-transformed (BEAS-2B(NNK)), and RA
      chemoprevented (BEAS-2B(NNK/RA)) HBE cells were used to conduct microarray
      analyses independently. Species increased in chemoprevented as compared with
      immortalized HBE cells (group I) and those augmented in chemoprevented as
      compared with transformed HBE cells (group II) included known RA-target genes as
      well as previously unrecognized RA-target genes in HBE cells. Unexpectedly, both
      groups were also enriched for interferon-stimulated genes. One interferon
      stimulated gene of particular interest was UBE1L, the ubiquitin-activating enzyme
      E1-like protein. UBE1L expression was also induced after prolonged RA-treatment
      of immortalized HBE cells. UBE1L mRNA was shown previously as repressed in
      certain lung cancer cell lines, directly implicating UBE1L in lung
      carcinogenesis. Notably, UBE1L immunoblot expression was reduced in a subset of
      malignant as compared with adjacent normal lung tissues that were examined.
      Immunohistochemical analyses were performed using a new assay developed to detect
      this species using rabbit polyclonal anti-UBE1L antibodies independently raised
      against the amino- or carboxyl-termini of UBE1L. Studies done on paraffin
      embedded and fixed tissues revealed abundant UBE1L, but low levels of cyclin D1
      expression in the normal human bronchial epithelium, indicating an inverse
      relationship existed between these species. To study this further, cotransfection
      into HBE cells of wild-type or mutant UBE1L species was accomplished. In a dose
      dependent manner, wild-type but not mutant UBE1L species repressed cyclin D1
      expression. This implicated UBE1L in a retinoid chemoprevention mechanism
      involving cyclin D1 repression described previously. Taken together, these
      findings directly implicate UBE1L as a candidate-pharmacologic target for lung
      cancer chemoprevention. These findings also provide a mechanistic basis for the
      tumor suppressive effects of UBE1L through cyclin D1 repression.

PMID- 15520224
TI  - Localization of cancer susceptibility genes by genome-wide single-nucleotide
      polymorphism linkage-disequilibrium mapping.
AB  - With the large numbers of single nucleotide polymorphisms (SNPs) available and
      new technologies that permit high throughput genotyping, we have investigated the
      possibility of the localization of disease genes with genome-wide panels of SNP
      markers and taking advantage of the linkage-disequilibrium (LD) between the
      disease gene and closely linked markers. For this purpose, we selected cases from
      the Ashkenazi Jewish population, in which the mutant alleles are expected to be
      identical by descent from a common founder and the regions of LD encompassing
      these mutant alleles are large. As a validation of this approach for
      localization, we performed two trials: one in autosomal recessive Bloom syndrome,
      in which a unique mutation of the BLM gene is present at elevated frequencies in
      cases, and the other in autosomal dominant hereditary nonpolyposis colorectal
      cancer (HNPCC), in which a unique mutation of MSH2 is present at elevated
      frequencies. In the Bloom syndrome trial, we genotyped 3,258 SNPs in 10 Jewish
      Bloom syndrome cases and 31 non-Bloom syndrome Jewish persons as a comparison
      group. In the HNPCC trial, we genotyped 8,549 SNPS in 13 Jewish HNPCC cases whose
      colon cancers exhibited microsatellite instability and in 63 healthy Jews as a
      comparison group. To identify significant associations, we performed (a) Fisher's
      exact test comparing genotypes at each locus in cases versus controls and (b) a
      haplotype analysis by estimating the frequency of haplotypes with the expectation
      maximization algorithm and comparing haplotype frequencies in cases versus
      controls by logistic regression and a maximum likelihood ratio method. In the
      Bloom syndrome trial, by Fisher's exact test, statistically significant
      association was detected at a single locus, TSC0754862, which is a locus 1.7
      million bp from BLM. Two-locus, three-locus, and four-locus haplotypes that
      included TSC0754862 and flanked BLM were also statistically more frequent in
      cases versus controls. In the HNPCC trial, although a significant P value was not
      obtained by the single SNP genotype analysis, significant associations were
      detected for several multilocus haplotypes in an 11-million-bp region that
      contained the MSH2 gene. This work demonstrates the power of the LD mapping
      approach in an isolated population and its general applicability to the
      identification of novel cancer-causing genes.

PMID- 15520225
TI  - Head and neck cancer: meeting summary and research opportunities.
AB  - Head and neck squamous cell carcinoma (HNSCC) is the most common malignant
      neoplasm arising in the mucosa of the upper aerodigestive tract. Nearly two
      thirds of patients present with advanced (stage III and IV) disease. Fifty
      percent of HNSCC patients die of their disease, and 5% of HNSCC patients per year
      will develop additional second primary tumors. Currently used therapeutic
      modalities (surgery, radiation, and/or chemotherapy) have been associated with
      rather modest improvements in patient survival. The Head and Neck Cancer:
      Research and Therapeutic Opportunities Workshop (held in Washington, DC, May 24
      26, 2004) was organized by the Division of Cancer Biology at the National Cancer
      Institute to identify research areas and directions that will advance
      understanding of HNSCC biology and accelerate clinical translation. The primary
      goal of the workshop was to identify the barriers that impede basic science
      discovery and the translation of these developments to the clinical setting. Over
      a 2.5-day period, experts in both HNSCC and other cancer-related fields met to
      identify and prioritize the key areas for future research. The overall consensus
      was that HNSCC is a relatively understudied malignancy and that investigations
      that focus on the biology of this tumor have the potential to impact
      significantly on the prevention and treatment of epithelial malignancies. The
      chief objective is to communicate these research goals to the cancer biology
      community and encourage more interest in HNSCC as a tumor model to test
      translational research hypotheses.

PMID- 15520226
TI  - The death receptor antagonist FAIM promotes neurite outgrowth by a mechanism that
      depends on ERK and NF-kapp B signaling.
AB  - Fas apoptosis inhibitory molecule (FAIM) is a protein identified as an antagonist
      of Fas-induced cell death. We show that FAIM overexpression fails to rescue
      neurons from trophic factor deprivation, but exerts a marked neurite growth
      promoting action in different neuronal systems. Whereas FAIM overexpression
      greatly enhanced neurite outgrowth from PC12 cells and sympathetic neurons grown
      with nerve growth factor (NGF), reduction of endogenous FAIM levels by RNAi
      decreased neurite outgrowth in these cells. FAIM overexpression promoted NF-kappa
      B activation, and blocking this activation by using a super-repressor I kappa B
      alpha or by carrying out experiments using cortical neurons from mice that lack
      the p65 NF-kappa B subunit prevented FAIM-induced neurite outgrowth. The effect
      of FAIM on neurite outgrowth was also blocked by inhibition of the Ras-ERK
      pathway. Finally, we show that FAIM interacts with both Trk and p75 neurotrophin
      receptor NGF receptors in a ligand-dependent manner. These results reveal a new
      function of FAIM in promoting neurite outgrowth by a mechanism involving
      activation of the Ras-ERK pathway and NF-kappa B.

PMID- 15520227
TI  - Cranial neural crest recycle surface integrins in a substratum-dependent manner
      to promote rapid motility.
AB  - Cell migration is essential for proper development of numerous structures derived
      from embryonic neural crest cells (NCCs). Although the migratory pathways of NCCs
      have been determined, the molecular mechanisms regulating NCC motility remain
      unclear. NCC migration is integrin dependent, and recent work has shown that
      surface expression levels of particular integrin alpha subunits are important
      determinants of NCC motility in vitro. Here, we provide evidence that rapid
      cranial NCC motility on laminin requires integrin recycling. NCCs showed both
      ligand- and receptor-specific integrin regulation in vitro. On laminin, NCCs
      accumulated internalized laminin but not fibronectin receptors over 20 min,
      whereas on fibronectin neither type of receptor accumulated internally beyond 2
      min. Internalized laminin receptors colocalized with receptor recycling vesicles
      and were subsequently recycled back to the cell surface. Blocking receptor
      recycling with bafilomycin A inhibited NCC motility on laminin, indicating that
      substratum-dependent integrin recycling is essential for rapid cranial neural
      crest migration.

PMID- 15520228
TI  - Netrins and neogenin promote myotube formation.
AB  - Differentiation of skeletal myoblasts into multinucleated myotubes is a multistep
      process orchestrated by several families of transcription factors, including
      myogenic bHLH and NFAT proteins. The activities of these factors and formation of
      myotubes are regulated by signal transduction pathways, but few extracellular
      factors that might initiate such signals have been identified. One exception is a
      cell surface complex containing promyogenic Ig superfamily members (CDO and BOC)
      and cadherins. Netrins and their receptors are established regulators of axon
      guidance, but little is known of their function outside the nervous system. We
      report here that myoblasts express the secreted factor netrin-3 and its receptor,
      neogenin. These proteins stimulate myotube formation and enhance myogenic bHLH-
      and NFAT-dependent transcription. Furthermore, neogenin binds to CDO in a cis
      fashion, and myoblasts lacking CDO are defective in responding to recombinant
      netrin. It is proposed that netrin-3 and neogenin may promote myogenic
      differentiation by an autocrine mechanism as components of a higher order complex
      of several promyogenic cell surface proteins.

PMID- 15520230
TI  - A role for BiP as an adjustor for the endoplasmic reticulum stress-sensing
      protein Ire1.
AB  - In the unfolded protein response, the type I transmembrane protein Ire1 transmits
      an endoplasmic reticulum (ER) stress signal to the cytoplasm. We previously
      reported that under nonstressed conditions, the ER chaperone BiP binds and
      represses Ire1. It is still unclear how this event contributes to the overall
      regulation of Ire1. The present Ire1 mutation study shows that the luminal domain
      possesses two subregions that seem indispensable for activity. The BiP-binding
      site was assigned not to these subregions, but to a region neighboring the
      transmembrane domain. Phenotypic comparison of several Ire1 mutants carrying
      deletions in the indispensable subregions suggests these subregions are
      responsible for multiple events that are prerequisites for activation of the
      overall Ire1 proteins. Unexpectedly, deletion of the BiP-binding site rendered
      Ire1 unaltered in ER stress inducibility, but hypersensitive to ethanol and high
      temperature. We conclude that in the ER stress-sensory system BiP is not the
      principal determinant of Ire1 activity, but an adjustor for sensitivity to
      various stresses.

PMID- 15520229
TI  - A cell sizer network involving Cln3 and Far1 controls entrance into S phase in
      the mitotic cycle of budding yeast.
AB  - Saccharomyces cerevisiae must reach a carbon source-modulated critical cell size,
      protein content per cell at the onset of DNA replication (Ps), in order to enter
      S phase. Cells grown in glucose are larger than cells grown in ethanol. Here, we
      show that an increased level of the cyclin-dependent inhibitor Far1 increases
      cell size, whereas far1 Delta cells start bud emergence and DNA replication at a
      smaller size than wild type. Cln3 Delta, far1 Delta, and strains overexpressing
      Far1 do not delay budding during an ethanol glucose shift-up as wild type does.
      Together, these findings indicate that Cln3 has to overcome Far1 to trigger Cln
      Cdc28 activation, which then turns on SBF- and MBF-dependent transcription. We
      show that a second threshold is required together with the Cln3/Far1 threshold
      for carbon source modulation of Ps. A new molecular network accounting for the
      setting of Ps is proposed.

PMID- 15520232
TI  - Enrollment, cost, and academic admission criteria of U.S. Dental schools by
      geographic region and institution type.
AB  - This article presents the academic qualifications of matriculating dental
      students (as indicated by overall undergraduate GPA, undergraduate science GPA,
      average DAT scores, and average PAT scores) and total cost of education for
      students at U.S. dental schools according to geographic location and funding
      sources. Dental schools were divided on the basis of geographic location
      (Northeast, South, Central, or West) and principal means of funding (public
      versus private). Average four-year total educational expenses as reported in the
      1996-97 and 2000-01 matriculation years were compared as well as undergraduate
      overall GPA, science GPA, DAT academic average, and PAT score. Public dental
      schools in the southern region cost significantly less than any other region of
      any funding type. Public dental schools in the western region had significantly
      higher average GPA, average science GPA, DAT academic average, and PAT scores
      among their matriculating classes than did any other region. Public dental
      schools from the western region also had the least amount of increase in
      projected four-year expenses between the two matriculation years compared.
      Excluding PAT scores, western public dental schools had the highest academic
      admission criteria of any region of either funding type.

PMID- 15520231
TI  - A pRb-independent mechanism preserves the postmitotic state in terminally
      differentiated skeletal muscle cells.
AB  - In skeletal muscle differentiation, the retinoblastoma protein (pRb) is
      absolutely necessary to establish definitive mitotic arrest. It is widely assumed
      that pRb is equally essential to sustain the postmitotic state, but this
      contention has never been tested. Here, we show that terminal proliferation
      arrest is maintained in skeletal muscle cells by a pRb-independent mechanism.
      Acute Rb excision from conditional knockout myotubes caused reexpression of E2F
      transcriptional activity, cyclin-E and -A kinase activities, PCNA, DNA ligase I,
      RPA, and MCM2, but did not induce DNA synthesis, showing that pRb is not
      indispensable to preserve the postmitotic state of these cells. Muscle-specific
      gene expression was significantly down-regulated, showing that pRb is constantly
      required for optimal implementation of the muscle differentiation program. Rb
      deleted myotubes were efficiently reactivated by forced expression of cyclin D1
      and Cdk4, indicating a functionally significant target other than pRb for these
      molecules. Finally, Rb removal induced no DNA synthesis even in pocket-protein
      null cells. Thus, the postmitotic state of myotubes is maintained by at least two
      mechanisms, one of which is pocket-protein independent.

PMID- 15520233
TI  - Reforming dental health professions education: a white paper.
AB  - The oral health education system is in need of major reform! This is especially
      apparent in university-based education for the health professions. So-called
      preclinical as well as clinical education simply has not kept pace with or been
      responsive enough to shifting patient demographics and patient/population desires
      and expectations, changing health system expectations, evolving interdisciplinary
      expertise and practice requirements, new scientific discoveries and scientific
      information, focus on quality improvement, and/or integration of emerging
      technologies. Moreover, university-based "dental education" is the most costly
      professional degree education within the entire university portfolio, and dental
      student accumulated debt is increasing each year well beyond national inflation
      estimates. Today, we have an enormous opportunity to explore major reforms in
      health professional education. Through the Santa Fe "process" of open and candid
      engagements and discussions (see www.santafegroup.org), we advance an argument as
      well as a national strategy that can enable major reforms in the oral health
      education system. We further suggest that major revisions can result in an
      outcome-based education system that prepares oral health professionals to meet
      both the needs of patients/families/communities and the requirements of a
      changing health system.

PMID- 15520234
TI  - An evaluation of two dental simulation systems: virtual reality versus
      contemporary non-computer-assisted.
AB  - Contemporary dental simulation systems were developed to improve dental students'
      transition from the preclinical laboratory to the clinic. The purpose of this
      study was to compare the efficacy of a virtual reality computer-assisted
      simulation system (VR) with a contemporary non-computer-assisted simulation
      system (CS). The objectives were to determine whether there were differences
      between the two systems in the quality of dental students' preparations and the
      amount of faculty instruction time. Students who completed their first year of
      dental school and had no previous experience preparing teeth were group matched
      according to their performance in the first-year Dental Anatomy laboratory course
      and assigned to VR (n=15) or CS (n=13). In the summer, they spent two weeks
      (approximately 3 hrs/day) executing amalgam and crown preparations on typodont
      teeth. Short presentations describing the preparations were given to both groups;
      however, preparation criteria were available on the computer for the VR group,
      while the CS group received handouts. Both groups could request feedback from
      faculty, although VR also obtained input from the computer. A log was kept of all
      student-faculty (S-F) interactions. Analysis of the data indicated significant
      differences between groups for the following variables: mean number of S-F
      interactions was sixteen for the VR group versus forty-two for the CS group; and
      mean time of S-F interactions was 1.9+/-2 minutes versus 4.0+/-3 minutes
      (p<0.001) for VR and CS, respectively. Faculty spent 44.3 hours "interacting"
      with twenty-eight students, averaging 0.5 hours per VR student and 2.8 hours per
      CS student. Thus, CS students received five times more instructional time from
      faculty than did VR students. There were no statistical differences in the
      quality of the preparations. While further study is needed to assess virtual
      reality technology, this decreased faculty time in instruction could impact the
      dental curriculum.

PMID- 15520235
TI  - Perceptions of dental schools from within and outside the university.
AB  - Perceptions of dental schools held by high-level administrators of their parent
      institutions and officials in the local community have great potential to
      influence the future of dental education. The intent of this investigation was to
      gain a preliminary knowledge of such perceptions at seven institutions in the
      United States and to use this information to formulate hypotheses that can
      provide the basis for further targeted investigations that provide evidence
      useful in decision making and planning processes within dental schools.
      Interviews with university administrators, executive directors of state dental
      associations, and state government officials in seven areas of the United States
      were conducted. The hypotheses drawn from these interviews are: 1) dental schools
      are generally too insular and need to interact more with their parent
      institutions and external community; 2) dental schools need to systematically and
      continually get the message of the value of their services out to the public and
      political constituencies; and 3) multidisciplinarity and integration with other
      units are important to university administrators but largely outside the concerns
      of those external to the university. We suggest that these hypotheses form the
      basis of subsequent, more targeted, follow-up investigations with the intent of
      formulating specific recommendations for action.

PMID- 15520236
TI  - Strategies for combating dental anxiety.
AB  - Dental anxiety and subsequent avoidance of dental care and deterioration of oral
      health pose a significant problem for the dental profession. In an attempt to
      elucidate preferences of anxious dental patients, we gathered survey data from
      121 persons at a small, private liberal arts college in the mid-Atlantic region
      of the United States. Half of the respondents experienced dental anxiety, and
      most of these (66 percent) attributed anxiety to fear of anticipated pain. The
      majority of anxious patients preferred a dentist to be friendly (93 percent),
      talkative (82 percent), and to have an office with adorned walls (89 percent) and
      a slightly cool temperature (63 percent). Patients who identified themselves as
      anxious also indicated that music in the background (89 percent) and magazines
      and books in the dental office (75 percent) were helpful. Anxious patients were
      more likely than non-anxious patients to prefer a male dentist (77 percent versus
      52 percent). This finding was especially marked among anxious male respondents,
      93 percent of whom preferred a male dentist compared to 73 percent of anxious
      female respondents. These survey data may assist dental professionals in
      understanding and combating patients' dental anxiety, in order to increase the
      frequency of dental visits and to prompt a corresponding restoration or
      maintenance of oral health.

PMID- 15520237
TI  - Cultural consistency in Australian dental students from two different ethnic
      backgrounds.
AB  - The objective of this study was to examine the value orientations of dental
      students from different ethnic backgrounds studying in Australian dental schools.
      A ninety-eight-item questionnaire was used to collect the data, including fifteen
      subscales developed consistent with the Kluckhohn and Strodtbeck value
      orientation model. To compare the value orientation structure and to determine if
      any ethnic differences existed, a multivariate analysis of variance called
      profile analysis was performed on the fifteen value subscales. Of the 401
      participants, 30.2 percent were Anglo-Australian and 44.9 percent were Asian. The
      remainder (24.9 percent) were "Other-background residents" or "Other
      international students." This article presents data from Asian (n=184) and Anglo
      Australian (n=124) background respondents. Mean age was 21.7 years (s.e. 0.35
      years) among Anglo-Australian and 20.8 years (s.e. 0.17 years) among Asians.
      Asians born overseas represented 70.7 percent (n=130) of this group. Of Australia
      born Asians (n=54), 90.6 percent were first-generation Australians. When
      comparing their value profile, we found a significant association between
      ethnicity and value orientation profile scores (p<0.05). Despite the significant
      overall result, the strength of the association (eta(2)=0.007) indicated that
      this effect was trivial relative to the unexplained variance in value
      orientation. The findings suggest that, behind an apparent ethnic diversity, a
      single distinctive value profile might exist to which the majority of dental
      students subscribe.

PMID- 15520238
TI  - The relationship between dental caries status and oral health attitudes and
      behavior in young Israeli adults.
AB  - The aim of this study was to investigate the epidemiologic relationship between
      oral health attitudes and behavior as measured by the Hiroshima University-Dental
      Behavioral Inventory (HU-DBI) and dental caries status using the DMF in a sample
      of young Israeli adults. The HU-DBI (in Hebrew) was used to survey 123 young
      Israeli army recruits (eighteen and nineteen years old). All participants
      submitted to a clinical and radiographic dental examination. Dental caries status
      was evaluated using the World Health Organization (WHO) caries diagnostic
      criteria for decayed, missing, and filled teeth and surfaces (DMFT and DMFS,
      respectively). Data were statistically analyzed. DMFT and DMFS scores, which
      measure dental disease, ranged from 0 to 24 (average 6.77) and from 0 to 48
      (average 10.95), respectively. There were sixteen (13 percent) caries free
      (DMF=0) participants. When relating the different DMF values to the HU-DBI
      responses, a statistically significant relation was found between seven items and
      DMF scores or their components and indices. The HU-DBI score ranged from 2 to 9
      (mean 5.8, SD=1.5). Low DS and DT values significantly correlated with a high
      total HU-DBI score (p<0.05); that is, subjects with low levels of dental disease
      had more positive oral health attitudes and behavior. In young Israeli adults,
      dental disease, as measured by DMF scores or their components, were related to HU
      DBI, which demonstrate the relationship of dental caries status with oral health
      behavior. Special emphasis should be given to improving patients' oral health
      attitudes and behaviors by providing patient education during treatment.

PMID- 15520239
TI  - Cheating behaviors of dental students.
AB  - There has always been some degree of cheating in educational institutions. Many
      students who have difficulty retaining information, or who are just too lazy to
      work, turn to cheating as an easy way to obtain high marks. The aims of this
      study were to investigate undergraduate dental students' attitudes about the
      seriousness of thirteen cheating behaviors and to determine the students'
      attitudes about justification for cheating. A multiple choice questionnaire was
      distributed to 200 undergraduate dental students at the Faculty of Dentistry of
      the Jordan University of Science and Technology in the second through the fifth
      year of the curriculum in order to rate thirteen cheating behaviors and report
      their degree of satisfaction with studying dentistry. The response rate was 100
      percent. Nine out of the thirteen cheating behaviors were considered as serious
      by about 85 percent of students. This majority also reported that they enjoyed
      studying dentistry compared to 10 percent who liked dentistry and 5 percent who
      disliked dentistry. Those 85 percent reported that they considered themselves to
      be ethical, while 10 percent selected somewhat ethical and 5 percent selected not
      ethical. This study revealed the importance of the issue of cheating and how it
      is evaluated by dental students who may benefit from educational programs as part
      of their curriculum.

PMID- 15520240
TI  - Incorporating bioterrorism training into dental education: report of ADA-ADEA
      terrorism and mass casualty curriculum development workshop.
AB  - Numerous areas have been identified in which the dental profession may be called
      upon to assist in the event of a major terrorism attack. In order to successfully
      fulfill these roles, dentists and dental students must be adequately prepared.
      Dental schools play a vital role in this preparation. Participants in an ADA-ADEA
      workshop reached consensus that all dental students should be trained in a core
      set of competencies enabling them to respond to a significant bioterrorism
      attack, help contain the spread of the attack, and participate in surveillance
      activities as appropriate upon direction of proper authorities. Further emergency
      response training should be available to individuals interested in gaining
      additional knowledge and skills to assist in response to an attack. Participants
      also concluded that, where possible, training should be seamlessly implemented
      into the current curriculum without the addition of new courses; however, the
      group also recognized the possible need for alternative models at some dental
      schools. Challenges to implementing bioterrorism training into the dental school
      curriculum include regional variation, management of the basic science
      curriculum, and financial considerations. The development of an exportable
      training package will be considered and funding sources explored in moving
      forward with the development of a curriculum.

PMID- 15520241
TI  - Pregnancy-associated malaria and the prospects for syndrome-specific antimalaria
      vaccines.
AB  - Aided by the Plasmodium falciparum genome project, recent discoveries regarding
      the molecular basis of malaria pathogenesis have led to a better understanding of
      the interactions between host and parasite. Although vaccines that prevent
      infection by malaria parasites remain only hopes for the future, there are now
      more immediate prospects for vaccines that protect against specific disease
      syndromes. Here, we discuss the latest advances in the development of a vaccine
      that specifically targets pregnancy-associated malaria (PAM).

PMID- 15520242
TI  - NF-kappaB and the immunoglobulin kappa gene enhancer.
AB  - Enhancers regulate lineage choice and the developmental timing of antigen
      receptor gene rearrangements. The transcription factor NF-kappaB has been
      implicated as a key component of the recombination and transcription activation
      potential of the immunoglobulin kappa chain gene intronic enhancer. Here, I
      discuss the implications of the new observation that an NF-kappaB binding site
      mutated enhancer in the correct biological context does not appear to affect
      kappa gene expression.

PMID- 15520243
TI  - ATM is required for efficient recombination between immunoglobulin switch
      regions.
AB  - Ataxia telangiectasia mutated (ATM) kinase is critical for initiating the
      signaling pathways that lead to cell cycle checkpoints and DNA double strand
      break repair. In the absence of ATM, humans and mice show a primary
      immunodeficiency that includes low serum antibody titers, but the role of ATM in
      antigen-driven immunoglobulin gene diversification has not been defined. Here, we
      show that although ATM is dispensable for somatic hypermutation, it is required
      for efficient class switch recombination (CSR). The defect in CSR is not due to
      alterations in switch region transcription, accessibility, DNA damage checkpoint
      protein recruitment, or short-range intra-switch region recombination. Only long
      range inter-switch recombination is defective, indicating an unexpected role for
      ATM in switch region synapsis during CSR.

PMID- 15520244
TI  - Essential roles of CD8+CD122+ regulatory T cells in the maintenance of T cell
      homeostasis.
AB  - Regulation of immune system is of paramount importance to prevent immune attacks
      against self-components. Mice deficient in the interleukin (IL)-2/IL-15 receptor
      beta chain, CD122, are model animals of such immune attacks and
      characteristically have a high number of abnormally activated T cells. Here, we
      show that the transfer of CD8+CD122+ cells into CD122-deficient neonates totally
      prevented the development of abnormal T cells. Furthermore, recombination
      activating gene-2-/- mice that received wild-type mice-derived CD8+CD122- cells
      died within 10 wk after cell transfer, indicating that normal CD8+CD122- cells
      become dangerously activated T cells in the absence of CD8+CD122+ T cells.
      CD8+CD122+ cells could control activated CD8+ or CD4+ T cells both in vivo and in
      vitro. Our results indicate that the CD8+CD122+ population includes naturally
      occurring CD8+ regulatory T cells that control potentially dangerous T cells.

PMID- 15520245
TI  - Lysosomal fusion is essential for the retention of Trypanosoma cruzi inside host
      cells.
AB  - Trypomastigotes, the highly motile infective forms of Trypanosoma cruzi, are
      capable of infecting several cell types. Invasion occurs either by direct
      recruitment and fusion of lysosomes at the plasma membrane, or through
      invagination of the plasma membrane followed by intracellular fusion with
      lysosomes. The lysosome-like parasitophorous vacuole is subsequently disrupted,
      releasing the parasites for replication in the cytosol. The role of this early
      residence within lysosomes in the intracellular cycle of T. cruzi has remained
      unclear. For several other cytosolic pathogens, survival inside host cells
      depends on an early escape from phagosomes before lysosomal fusion. Here, we show
      that when lysosome-mediated T. cruzi invasion is blocked through
      phosophoinositide 3-kinase inhibition, a significant fraction of the internalized
      parasites are not subsequently retained inside host cells for a productive
      infection. A direct correlation was observed between the lysosomal fusion rates
      after invasion and the intracellular retention of trypomastigotes. Thus,
      formation of a parasitophorous vacuole with lysosomal properties is essential for
      preventing these highly motile parasites from exiting host cells and for allowing
      completion of the intracellular life cycle.

PMID- 15520246
TI  - The role of CXCR4 in maintaining peripheral B cell compartments and humoral
      immunity.
AB  - The chemokine receptor CXCR4 is expressed in B cells at multiple stages of their
      development. CXCR4 function in humoral immunity has not been fully investigated.
      We have generated gene-targeted mice in which CXCR4 can be selectively
      inactivated in B cells and have shown that it is required for retention of B cell
      precursors in the bone marrow. CXCR4-deficient B cell precursors that migrated
      prematurely became localized in splenic follicles despite their unresponsiveness
      to CXCL13. Concomitantly, mature B cell populations were reduced in the splenic
      marginal zone and primary follicles, and in the peritoneal cavity in the mutant
      animals, as were T-independent antibody responses. In addition, aberrant B cell
      follicles formed ectopically in intestinal lamina propria around Peyer's patches.
      These findings establish an important role for CXCR4 in regulating homeostasis of
      B cell compartmentalization and humoral immunity.

PMID- 15520247
TI  - The molecular adapter Carma1 controls entry of IkappaB kinase into the central
      immune synapse.
AB  - Carma1 (also known as caspase recruitment domain [CARD]11, Bimp3) is a CARD
      containing membrane-associated guanylate kinase family protein that plays an
      essential role in antigen receptor-induced nuclear factor kappaB activation. We
      investigated the role of Carma1 in the assembly of signaling molecules at the
      immune synapse using a peptide-specific system. We report that Carma1 is
      essential for peptide-induced interleukin 2 and interferon gamma production, but
      dispensable for proliferation in T cells. Recruitment and distribution of T cell
      receptor, lymphocyte function associated 1, lipid rafts, and protein kinase C
      (PKC)theta; to central and peripheral immune synapse regions occur normally in
      Carma1-/- T cells. Carma1 controls entry of IkappaB kinase (IKK) into lipid raft
      aggregates and the central region of the immune synapse, as well as activation of
      IKK downstream of PKC. Our data provide the first genetic evidence on a new class
      of molecular scaffold that controls entry of defined signaling components, IKK,
      into the central supramolecular activation cluster at T cell-antigen-presenting
      cell interfaces without having any apparent effect on the overall organization
      and formation of immune synapses.

PMID- 15520248
TI  - Loss of Bim allows precursor B cell survival but not precursor B cell
      differentiation in the absence of interleukin 7.
AB  - Interleukin (IL)-7 is a stromal cell-derived cytokine required for the survival,
      proliferation, and differentiation of B cell precursors. Members of the Bcl-2
      family of proteins are known to have profound effects on lymphocyte survival, but
      not lymphocyte differentiation. To distinguish the relative dependence on IL-7 of
      B cell precursor survival versus B cell differentiation, the combined effects of
      lack of IL-7 and lack of the proapoptotic Bcl-2 relative, Bim, were studied. Bim
      is expressed to varying degrees in all B cell precursors and B cells. Lack of Bim
      compensated for lack of IL-7 in the survival of pro-, pre-, and immature B cells;
      however, lack of Bim did not substitute for the requirement for IL-7 in B cell
      precursor differentiation or B cell precursor proliferation. Precursor B cell
      survival is more dependent on sufficient levels of IL-7 than precursor B cell
      differentiation because the number of B cells and their precursors were reduced
      by half in mice heterozygous for IL-7 expression, but were restored to normal
      numbers in mice also lacking Bim. Hence, Bim and IL-7 work together to control
      the survival of B cell precursors and the number of B cells that exist in
      animals.

PMID- 15520249
TI  - Evidence for the involvement of VAR2CSA in pregnancy-associated malaria.
AB  - In Plasmodium falciparum-endemic areas, pregnancy-associated malaria (PAM) is an
      important health problem. The condition is precipitated by accumulation of
      parasite-infected erythrocytes (IEs) in the placenta, and this process is
      mediated by parasite-encoded variant surface antigens (VSA) binding to
      chondroitin sulfate A (CSA). Parasites causing PAM express unique VSA types,
      VSAPAM, which can be serologically classified as sex specific and parity
      dependent. It is sex specific because men from malaria-endemic areas do not
      develop VSAPAM antibodies; it is parity dependent because women acquire anti
      VSAPAM immunoglobulin (Ig) G as a function of parity. Previously, it was shown
      that transcription of var2csa is up-regulated in placental parasites and
      parasites selected for CSA binding. Here, we show the following: (a) that VAR2CSA
      is expressed on the surface of CSA-selected IEs; (b) that VAR2CSA is recognized
      by endemic plasma in a sex-specific and parity-dependent manner; (c) that high
      anti-VAR2CSA IgG levels can be found in pregnant women from both West and East
      Africa; and (d) that women with high plasma levels of anti-VAR2CSA IgG give birth
      to markedly heavier babies and have a much lower risk of delivering low birth
      weight children than women with low levels.

PMID- 15520251
TI  - Tumor-associated CD75s gangliosides and CD75s-bearing glycoproteins with
      Neu5Acalpha2-6Galbeta1-4GlcNAc-residues are receptors for the anticancer drug
      rViscumin.
AB  - The anticancer drug rViscumin, currently under clinical development, has been
      shown in previous studies to be a sialic acid specific ribosome inactivating
      protein (RIP). Comparative binding assays with the CD75s-specific monoclonal
      antibodies HB6 and J3-89 revealed rViscumin to be a CD75s-specific RIP due to
      identical binding characteristics toward CD75s gangliosides. The receptor
      gangliosides are IV6nLc4Cer, VI6nLc6Cer, and the newly characterized ganglioside
      VIII6nLc8Cer, all three carrying the Neu5Acalpha2-6Galbeta1-4GlcNAc motif. To
      elucidate the clinical potential of the rViscumin targets, CD75s gangliosides
      were determined in several randomly collected gastrointestinal tumors. The
      majority of the tumors showed an enhanced expression of CD75s gangliosides
      compared with the unaffected tissues. The rViscumin binding specificity was
      further investigated with reference glycoproteins carrying sialylated and
      desialylated type II N-glycans. Comparative Western blots of rViscumin and ricin,
      an rViscumin homologous but galactoside-specific RIP, revealed specific
      recognition of type II N-glycans with CD75s determinants by rViscumin, whereas
      ricin failed to react with terminally sialylated oligosaccharides such as CD75s
      motifs and others. This strict binding specificity of rViscumin and the increased
      expression of CD75s gangliosides in various tumors suggest this anticancer drug
      as a promising candidate for an individualised adjuvant therapy of human tumors.

PMID- 15520253
TI  - Mouse inbred strain sequence information and yin-yang crosses for quantitative
      trait locus fine mapping.
AB  - The shared ancestry of mouse inbred strains, together with the availability of
      sequence and phenotype information, is a resource that can be used to map
      quantitative trait loci (QTL). The difficulty in using only sequence information
      lies in the fact that in most instances the allelic state of the QTL cannot be
      unambiguously determined in a given strain. To overcome this difficulty, the
      performance of multiple crosses between various inbred strains has been proposed.
      Here we suggest and evaluate a general approach, which consists of crossing the
      two strains used initially to map the QTL and any new strain. We have termed
      these crosses "yin-yang," because they are complementary in nature as shown by
      the fact that the QTL will necessarily segregate in only one of the crosses. We
      used the publicly available SNP database of chromosome 16 to evaluate the mapping
      resolution achievable through this approach. Although on average the improvement
      of mapping resolution using only four inbred strains was relatively small (i.e.,
      reduction of the QTL-containing interval by half at most), we found a great
      degree of variability among different regions of chromosome 16 with regard to
      mapping resolution. This suggests that with a large number of strains in hand,
      selecting a small number of strains may provide a significant contribution to the
      fine mapping of QTL.

PMID- 15520252
TI  - The relative roles in vivo of Saccharomyces cerevisiae Pol eta, Pol zeta, Rev1
      protein and Pol32 in the bypass and mutation induction of an abasic site, T-T (6
      4) photoadduct and T-T cis-syn cyclobutane dimer.
AB  - We have investigated the relative roles in vivo of Saccharomyces cerevisiae DNA
      polymerase eta, DNA polymerase zeta, Rev1 protein, and the DNA polymerase delta
      subunit, Pol32, in the bypass of an abasic site, T-T (6-4) photoadduct and T-T
      cis-syn cyclobutane dimer, by transforming strains deleted for RAD30, REV3, REV1,
      or POL32 with duplex plasmids carrying one of these DNA lesions located within a
      28-nucleotide single-stranded region. DNA polymerase eta was found to be involved
      only rarely in the bypass of the T-T (6-4) photoadduct or the abasic sites in the
      sequence context used, although, as expected, it was solely responsible for the
      bypass of the T-T dimer. We argue that DNA polymerase zeta, rather than DNA
      polymerase delta as previously suggested, is responsible for insertion in bypass
      events other than those in which polymerase eta performs this function. However,
      DNA polymerase delta is involved indirectly in mutagenesis, since the strain
      lacking its Pol32 subunit, known to be deficient in mutagenesis, shows as little
      bypass of the T-T (6-4) photoadduct or the abasic sites as those deficient in Pol
      zeta or Rev1. In contrast, bypass of the T-T dimer in the pol32delta strain
      occurs at the wild-type frequency.

PMID- 15520254
TI  - Drosophila Su(Hw) insulator can stimulate transcription of a weakened yellow
      promoter over a distance.
AB  - The insulator element from the gypsy transposon is a DNA sequence that blocks
      activation of a promoter by a transcriptional enhancer when placed between them.
      The insulator contains reiterated binding sites for the Suppressor of Hairy-wing
      [Su(Hw)] zinc-finger protein. A protein encoded by another gene, modifier of mdg4
      [mod(mdg4)], is also required for the enhancer-blocking activity of the Su(Hw)
      insulator. Here we present evidence that the Su(Hw) insulator activates a
      weakened yellow promoter at a distance. Deletion of the upstream promoter region
      (UPR), located close by the TATA box, significantly reduces yellow expression.
      The Su(Hw) insulator placed at different positions relative to the yellow
      promoter partially compensates for loss of the UPR. Su(Hw) is able to stimulate
      yellow expression even if it is located at a 5-kb distance from the promoter. The
      stimulatory activity depends on the number of Su(Hw)-binding sites. Mutational
      analysis demonstrates that only the DNA-binding domain and adjacent regions of
      the Su(Hw) protein are required for stimulation of yellow transcription.

PMID- 15520255
TI  - Detection of chromosomal rearrangements derived from homologous recombination in
      four mapping populations of Brassica napus L.
AB  - Genetic maps of Brassica napus were constructed from four segregating populations
      of doubled haploid lines. Each mapping population had the same male parent and
      used the same set of RFLP probes, facilitating the construction of a consensus
      map. Chromosomal rearrangements were identified in each population by molecular
      marker analysis and were classified as de novo homologous nonreciprocal
      transpositions (HNRTs), preexisting HNRTs, and homologous reciprocal
      transpositions (HRTs). Ninety-nine de novo HNRTs were identified by the presence
      of a few lines having duplication of a chromosomal region and loss of the
      corresponding homologous region. These de novo HNRTs were more prevalent in one
      population that had a resynthesized B. napus as a parent. Preexisting HNRTs were
      identified by fragment duplication or fragment loss in many DH lines due to the
      segregation of HNRTs preexisting in one of the parents. Nine preexisting HNRTs
      were identified in the three populations involving natural B. napus parents,
      which likely originated from previous homologous exchanges. The male parent had a
      previously described HRT between N7 and N16, which segregated in each population.
      These data suggest that chromosomal rearrangements caused by homologous
      recombination are widespread in B. napus. The effects of these rearrangements on
      allelic and phenotypic diversity are discussed.

PMID- 15520257
TI  - Naturally segregating quantitative trait loci affecting wing shape of Drosophila
      melanogaster.
AB  - Variation in vein position and wing shape of Drosophila melanogaster depends on
      many genes. In the following, we report the results of a QTL analysis of wing
      shape in D. melanogaster. We identified QTL responsible for natural variation for
      wing shape and analyzed their interactions with developmental genetic signaling
      pathways important for vein positioning. The QTL analysis indicated that the
      total number of QTL segregating in this population is likely to be very large.
      The locations of putative QTL identified in this study were compared to those
      identified in previous studies and, while there is more correspondence across
      studies than expected by chance on the third chromosome, the studies appear to
      have identified different QTL. Using a complementation design, we tested for
      interactions among these QTL with the Hedgehog and Decapentaplegic signaling
      pathways, which are important for the development and position of vein pairs L3
      L4 and L2-L5. Three QTL showed strong interactions with these two pathways,
      supporting the hypothesis that these QTL are involved in these pathways.
      Naturally segregating variation can therefore act through known signaling
      pathways to produce variation in vein position.

PMID- 15520256
TI  - Trans-splicing of the mod(mdg4) complex locus is conserved between the distantly
      related species Drosophila melanogaster and D. virilis.
AB  - The modifier of mdg4, mod(mdg4), locus in Drosophila melanogaster represents a
      new type of complex gene in which functional diversity is resolved by mRNA trans
      splicing. A protein family of >30 transcriptional regulators, which are supposed
      to be involved in higher-order chromatin structure, is encoded by both DNA
      strands of this locus. Mutations in mod(mdg4) have been identified independently
      in a number of genetic screens involving position-effect variegation, modulation
      of chromatin insulators, apoptosis, pathfinding of nerve cells, and chromosome
      pairing, indicating pleiotropic effects. The unusual gene structure and mRNA
      trans-splicing are evolutionary conserved in the distantly related species
      Drosophila virilis. Chimeric mod(mdg4) transcripts encoded from nonhomologous
      chromosomes containing the splice donor from D. virilis and the acceptor from D.
      melanogaster are produced in transgenic flies. We demonstrate that a significant
      amount of protein can be produced from these chimeric mRNAs. The evolutionary and
      functional conservation of mod(mdg4) and mRNA trans-splicing in both Drosophila
      species is furthermore demonstrated by the ability of D. virilis mod(mdg4)
      transgenes to rescue recessive lethality of mod(mdg4) mutant alleles in D.
      melanogaster.

PMID- 15520258
TI  - Haplotype analysis of the beta2 adrenergic receptor gene and risk of myocardial
      infarction in humans.
AB  - Polymorphisms in the beta2 adrenergic receptor (ADRB2), in particular G16R, Q27E,
      and T164I, have been implicated in the pathogenesis of cardiovascular and
      metabolic phenotypes. However, no prospective, genetic-epidemiological data are
      available on the risk of cardiovascular disease associated with these variants.
      Using DNA samples collected at baseline in a prospective cohort of 14,916
      initially healthy American men, we evaluated the G16R, Q27E, and T164I
      polymorphisms among 523 individuals who subsequently developed myocardial
      infarction and among 2092 individuals who remained free of reported
      cardiovascular events during follow-up. The haplotype frequency distribution was
      significantly different among cases and controls (chi(2)(7d.f.) = 20.92, P =
      0.0039). Haplotype-based logistic regression, adjusting for age, smoking, and
      randomized treatment group, indicated that G16-Q27-I164 (odds ratio 0.178, 95%
      C.I. 0.043-0.737, P = 0.017) and (non-G16-Q27)-T164 (odds ratio 1.235, 95% C.I.
      1.031-1.480, P = 0.022) haplotypes were significantly associated with altered
      risk of myocardial infarction. These findings remained after further adjustment
      for BMI, history of hypertension, and presence or absence of diabetes. In
      conclusion, variation in haplotype frequencies for the beta2 adrenergic receptor
      gene was found to be associated with risk of myocardial infarction.

PMID- 15520259
TI  - The novel Drosophila tim(blind) mutation affects behavioral rhythms but not
      periodic eclosion.
AB  - Circadian clock function depends on the tightly regulated exclusion or presence
      of clock proteins within the nucleus. A newly induced long-period timeless
      mutant, tim(blind), encodes a constitutively hypophosphorylated TIM protein. The
      mutant protein is not properly degraded by light, and tim(blind) flies show
      abnormal behavioral responses to light pulses. This is probably caused by
      impaired nuclear accumulation of TIM(BLIND) protein, which we observed in brain
      pacemaker neurons and photoreceptor cells of the compound eye. tim(blind) encodes
      two closely spaced amino acid changes compared to the wild-type TIM protein; one
      of them is within a putative nuclear export signal of TIM. Under constant
      conditions, tim(blind) flies exhibit 26-hr free-running locomotor rhythms, which
      are not correlated with a period lengthening of eclosion rhythms and period
      luciferase reporter-gene oscillations. Therefore it seems possible that TIM--in
      addition to its well-established role as core clock factor--functions as a clock
      output factor, involved in determining the period length of adult locomotor
      rhythms.

PMID- 15520260
TI  - High genetic diversity in the chemoreceptor superfamily of Caenorhabditis
      elegans.
AB  - We investigated genetic polymorphism in the Caenorhabditis elegans srh and str
      chemoreceptor gene families, each of which consists of approximately 300 genes
      encoding seven-pass G-protein-coupled receptors. Almost one-third of the genes in
      each family are annotated as pseudogenes because of apparent functional defects
      in N2, the sequenced wild-type strain of C. elegans. More than half of these
      "pseudogenes" have only one apparent defect, usually a stop codon or deletion. We
      sequenced the defective region for 31 such genes in 22 wild isolates of C.
      elegans. For 10 of the 31 genes, we found an apparently functional allele in one
      or more wild isolates, suggesting that these are not pseudogenes but instead
      functional genes with a defective allele in N2. We suggest the term "flatliner"
      to describe genes whose functional vs. pseudogene status is unclear.
      Investigations of flatliner gene positions, d(N)/d(S) ratios, and phylogenetic
      trees indicate that they are not readily distinguished from functional genes in
      N2. We also report striking heterogeneity in the frequency of other polymorphisms
      among these genes. Finally, the large majority of polymorphism was found in just
      two strains from geographically isolated islands, Hawaii and Madeira. This
      suggests that our sampling of wild diversity in C. elegans is narrow and that
      identification of additional strains from similarly isolated regions will greatly
      expand the diversity available for study.

PMID- 15520261
TI  - Mapping multiple Quantitative Trait Loci by Bayesian classification.
AB  - We developed a classification approach to multiple quantitative trait loci (QTL)
      mapping built upon a Bayesian framework that incorporates the important prior
      information that most genotypic markers are not cotransmitted with a QTL or their
      QTL effects are negligible. The genetic effect of each marker is modeled using a
      three-component mixture prior with a class for markers having negligible effects
      and separate classes for markers having positive or negative effects on the
      trait. The posterior probability of a marker's classification provides a natural
      statistic for evaluating credibility of identified QTL. This approach performs
      well, especially with a large number of markers but a relatively small sample
      size. A heat map to visualize the results is proposed so as to allow
      investigators to be more or less conservative when identifying QTL. We validated
      the method using a well-characterized data set for barley heading values from the
      North American Barley Genome Mapping Project. Application of the method to a new
      data set revealed sex-specific QTL underlying differences in glucose-6-phosphate
      dehydrogenase enzyme activity between two Drosophila species. A simulation study
      demonstrated the power of this approach across levels of trait heritability and
      when marker data were sparse.

PMID- 15520262
TI  - Genetic analysis of RpL38 and RpL5, two minute genes located in the centric
      heterochromatin of chromosome 2 of Drosophila melanogaster.
AB  - The Minute mutations of Drosophila melanogaster are thought to disrupt genes that
      encode ribosomal proteins (RPs) and thus impair ribosome function and protein
      synthesis. However, relatively few Minutes have been tied to distinct RP genes
      and more Minute loci are likely to be discovered. We have identified point
      mutations in RpL38 and RpL5 in a screen for factors limiting for growth of the D.
      melanogaster wing. Here, we present the first genetic characterization of these
      loci. RpL38 is located in the centric heterochromatin of chromosome arm 2R and is
      identical to a previously identified Minute, M(2)41A, and also l(2)41Af. RpL5 is
      located in the 2L centric heterochromatin and defines a novel Minute gene. Both
      genes are haplo-insufficient, as heterozygous mutations cause the classic Minute
      phenotypes of small bristles and delayed development. Surprisingly, we find that
      RpL38(-)/+ and RpL5(-)/+ adult flies have abnormally large wings as a result of
      increased cell size, emphasizing the importance of translational regulation in
      the control of growth. Taken together, our data provide new molecular and genetic
      information on two previously uncharacterized Minute/RP genes, the
      heterochromatic regions in which they reside, and the role of their protein
      products in the control of organ growth.

PMID- 15520263
TI  - A spatial statistical model for landscape genetics.
AB  - Landscape genetics is a new discipline that aims to provide information on how
      landscape and environmental features influence population genetic structure. The
      first key step of landscape genetics is the spatial detection and location of
      genetic discontinuities between populations. However, efficient methods for
      achieving this task are lacking. In this article, we first clarify what is
      conceptually involved in the spatial modeling of genetic data. Then we describe a
      Bayesian model implemented in a Markov chain Monte Carlo scheme that allows
      inference of the location of such genetic discontinuities from individual geo
      referenced multilocus genotypes, without a priori knowledge on populational units
      and limits. In this method, the global set of sampled individuals is modeled as a
      spatial mixture of panmictic populations, and the spatial organization of
      populations is modeled through the colored Voronoi tessellation. In addition to
      spatially locating genetic discontinuities, the method quantifies the amount of
      spatial dependence in the data set, estimates the number of populations in the
      studied area, assigns individuals to their population of origin, and detects
      individual migrants between populations, while taking into account uncertainty on
      the location of sampled individuals. The performance of the method is evaluated
      through the analysis of simulated data sets. Results show good performances for
      standard data sets (e.g., 100 individuals genotyped at 10 loci with 10 alleles
      per locus), with high but also low levels of population differentiation (e.g.,
      FST<0.05). The method is then applied to a set of 88 individuals of wolverines
      (Gulo gulo) sampled in the northwestern United States and genotyped at 10
      microsatellites.

PMID- 15520265
TI  - Transmission ratio distortion in offspring of mouse heterozygous carriers of a
      (7.18) Robertsonian translocation.
AB  - Transmission ratio distortion (TRD) is defined as a significant departure from
      expected Mendelian ratios of inheritance of an allele or chromosome. TRD is
      observed among specific regions of the mouse and human genome and is frequently
      associated with chromosome rearrangements such as Robertsonian (Rb) chromosomes.
      We intercrossed mice heterozygous for a (7.18) Rb translocation and genotyped
      chromosomes 7 and 18 in 1812 individuals, 47% of which were informative for
      chromosome segregation. We substantiated previous findings that females were less
      likely than expected to transmit the Rb chromosome to their offspring.
      Surprisingly, however, we report that heterozygous males transmitted the Rb
      translocation chromosome significantly more frequently than the acrocentrics. The
      transmission of the Rb chromosome was not significantly influenced by either the
      sex of the Rb grandparent or the strain of the Rb.

PMID- 15520264
TI  - Distribution of Activator (Ac) throughout the maize genome for use in regional
      mutagenesis.
AB  - A collection of Activator (Ac)-containing, near-isogenic W22 inbred lines has
      been generated for use in regional mutagenesis experiments. Each line is
      homozygous for a single, precisely positioned Ac element and the Ds reporter, r1
      sc:m3. Through classical and molecular genetic techniques, 158 transposed Ac
      elements (tr-Acs) were distributed throughout the maize genome and 41 were
      precisely placed on the linkage map utilizing multiple recombinant inbred
      populations. Several PCR techniques were utilized to amplify DNA fragments
      flanking tr-Ac insertions up to 8 kb in length. Sequencing and database searches
      of flanking DNA revealed that the majority of insertions are in hypomethylated,
      low- or single-copy sequences, indicating an insertion site preference for genic
      sequences in the genome. However, a number of Ac transposition events were to
      highly repetitive sequences in the genome. We present evidence that suggests Ac
      expression is regulated by genomic context resulting in subtle variations in Ac
      mediated excision patterns. These tr-Ac lines can be utilized to isolate genes
      with unknown function, to conduct fine-scale genetic mapping experiments, and to
      generate novel allelic diversity in applied breeding programs.

PMID- 15520266
TI  - The structured ancestral selection graph and the many-demes limit.
AB  - We show that the unstructured ancestral selection graph applies to part of the
      history of a sample from a population structured by restricted migration among
      subpopulations, or demes. The result holds in the limit as the number of demes
      tends to infinity with proportionately weak selection, and we have also made the
      assumptions of island-type migration and that demes are equivalent in size. After
      an instantaneous sample-size adjustment, this structured ancestral selection
      graph converges to an unstructured ancestral selection graph with a mutation
      parameter that depends inversely on the migration rate. In contrast, the
      selection parameter for the population is independent of the migration rate and
      is identical to the selection parameter in an unstructured population. We show
      analytically that estimators of the migration rate, based on pairwise sequence
      differences, derived under the assumption of neutrality should perform equally
      well in the presence of weak selection. We also modify an algorithm for
      simulating genealogies conditional on the frequencies of two selected alleles in
      a sample. This permits efficient simulation of stronger selection than was
      previously possible. Using this new algorithm, we simulate gene genealogies under
      the many-demes ancestral selection graph and identify some situations in which
      migration has a strong effect on the time to the most recent common ancestor of
      the sample. We find that a similar effect also increases the sensitivity of the
      genealogy to selection.

PMID- 15520267
TI  - Genomic heterogeneity of background substitutional patterns in Drosophila
      melanogaster.
AB  - Mutation is the underlying force that provides the variation upon which
      evolutionary forces can act. It is important to understand how mutation rates
      vary within genomes and how the probabilities of fixation of new mutations vary
      as well. If substitutional processes across the genome are heterogeneous, then
      examining patterns of coding sequence evolution without taking these underlying
      variations into account may be misleading. Here we present the first rigorous
      test of substitution rate heterogeneity in the Drosophila melanogaster genome
      using almost 1500 nonfunctional fragments of the transposable element DNAREP1_DM.
      Not only do our analyses suggest that substitutional patterns in heterochromatic
      and euchromatic sequences are different, but also they provide support in favor
      of a recombination-associated substitutional bias toward G and C in this species.
      The magnitude of this bias is entirely sufficient to explain recombination
      associated patterns of codon usage on the autosomes of the D. melanogaster
      genome. We also document a bias toward lower GC content in the pattern of small
      insertions and deletions (indels). In addition, the GC content of noncoding DNA
      in Drosophila is higher than would be predicted on the basis of the pattern of
      nucleotide substitutions and small indels. However, we argue that the fast
      turnover of noncoding sequences in Drosophila makes it difficult to assess the
      importance of the GC biases in nucleotide substitutions and small indels in
      shaping the base composition of noncoding sequences.

PMID- 15520268
TI  - Analysis of conditional paralytic mutants in Drosophila sarco-endoplasmic
      reticulum calcium ATPase reveals novel mechanisms for regulating membrane
      excitability.
AB  - Individual contributions made by different calcium release and sequestration
      mechanisms to various aspects of excitable cell physiology are incompletely
      understood. SERCA, a sarco-endoplasmic reticulum calcium ATPase, being the main
      agent for calcium uptake into the ER, plays a central role in this process. By
      isolation and extensive characterization of conditional mutations in the
      Drosophila SERCA gene, we describe novel roles of this key protein in
      neuromuscular physiology and enable a genetic analysis of SERCA function. At
      motor nerve terminals, SERCA inhibition retards calcium sequestration and reduces
      the amplitude of evoked excitatory junctional currents. This suggests a direct
      contribution of store-derived calcium in determining the quantal content of
      evoked release. Conditional paralysis of SERCA mutants is also marked by
      prolonged neural activity-driven muscle contraction, thus reflecting the
      phylogenetically conserved role of SERCA in terminating contraction. Further
      analysis of ionic currents from mutants uncovers SERCA-dependent mechanisms
      regulating voltage-gated calcium channels and calcium-activated potassium
      channels that together control muscle excitability. Finally, our identification
      of dominant loss-of-function mutations in SERCA indicates novel intra- and
      intermolecular interactions for SERCA in vivo, overlooked by current structural
      models.

PMID- 15520270
TI  - On the effect of fluctuating recombination rates on the decorrelation of gene
      histories in the human genome.
AB  - We show how to incorporate fluctuations of the recombination rate along the
      chromosome into standard gene-genealogical models for the decorrelation of gene
      histories. This enables us to determine how small-scale fluctuations (Poissonian
      hot-spot model) and large-scale variations (Kong et al. 2002) of the
      recombination rate influence this decorrelation. We find that the empirically
      determined large-scale variations of the recombination rate give rise to a
      significantly slower decay of correlations compared to the standard, unstructured
      gene-genealogical model assuming constant recombination rate. A model with long
      range recombination-rate variations and with demographic structure (divergent
      population) is found to be consistent with the empirically observed slow
      decorrelation of gene histories. Conversely, we show that small-scale
      recombination-rate fluctuations do not alter the large-scale decorrelation of
      gene histories.

PMID- 15520269
TI  - The Zn(II)2Cys6 putative Aspergillus nidulans transcription factor repressor of
      sexual development inhibits sexual development under low-carbon conditions and in
      submersed culture.
AB  - Here we have characterized the putative Zn(II)2Cys6 transcription factor RosA
      from the filamentous fungus Aspergillus nidulans. The rosA gene encodes a protein
      of 713 aa, which shares 38% sequence similarity to Pro1 from Sordaria macrospora.
      In contrast to Pro1, which promotes the transition from protoperithecia to
      perithecia, RosA is a negative regulator of sexual development in A. nidulans.
      Transcript levels of rosA were usually very low and were only transiently
      upregulated upon carbon starvation and at 12 hr of asexual development. Deletion
      of rosA only slightly induced fruiting-body formation under standard culture
      conditions, but enabled sexual development under low-glucose and high-osmolarity
      conditions and the production of Hulle cells under submersed growth conditions.
      Stimulation of fruiting-body formation on agar surfaces was dependent on veA. In
      delta rosA strains, transcript levels of the sexual developmental regulators
      nsdD, veA, and stuA were increased. Overexpression of rosA led to a reduction of
      hyphal growth and to a fluffy phenotype. Post-transcriptional regulation of RosA,
      with a regulated accumulation in the nucleus, was shown using a RosA-GFP fusion
      protein. We propose that RosA represses sexual development upon integration of
      several environmental signals.

PMID- 15520271
TI  - How old is the most recent ancestor of two copies of an allele?
AB  - An important clue to the evolutionary history of an allele is the structure of
      the neighboring region of the genome, which we term the genomic background of the
      allele. Consider two copies of the allele. How similar we expect their genomic
      background to be is strongly influenced by the age of their most recent common
      ancestor (MRCA). We apply diffusion theory, first used by Motoo Kimura as a tool
      for predicting the changes in allele frequencies over time and developed by him
      in many articles in this journal, to prove a variety of new results on the age of
      the MRCA under the simplest demographic assumptions. In particular, we show that
      the expected age of the MRCA of two copies of an allele with population frequency
      f is just 2Nf generations, where N is the effective population size. Our results
      are a first step in running exact coalescent simulations, where we also simulate
      the history of the population frequency of an allele.

PMID- 15520272
TI  - Fluorescence imaging of two-photon linear dichroism: cholesterol depletion
      disrupts molecular orientation in cell membranes.
AB  - The plasma membrane of cells is an ordered environment, giving rise to
      anisotropic orientation and restricted motion of molecules and proteins residing
      in the membrane. At the same time as being an organized matrix of defined
      structure, the cell membrane is heterogeneous and dynamic. Here we present a
      method where we use fluorescence imaging of linear dichroism to measure the
      orientation of molecules relative to the cell membrane. By detecting linear
      dichroism as well as fluorescence anisotropy, the orientation parameters are
      separated from dynamic properties such as rotational diffusion and homo energy
      transfer (energy migration). The sensitivity of the technique is enhanced by
      using two-photon excitation for higher photo-selection compared to single photon
      excitation. We show here that we can accurately image lipid organization in whole
      cell membranes and in delicate structures such as membrane nanotubes connecting
      two cells. The speed of our wide-field imaging system makes it possible to image
      changes in orientation and anisotropy occurring on a subsecond timescale. This is
      demonstrated by time-lapse studies showing that cholesterol depletion rapidly
      disrupts the orientation of a fluorophore located within the hydrophobic region
      of the cell membrane but not of a surface bound probe. This is consistent with
      cholesterol having an important role in stabilizing and ordering the lipid tails
      within the plasma membrane.

PMID- 15520273
TI  - PAF1-complex-mediated histone methylation of FLOWERING LOCUS C chromatin is
      required for the vernalization-responsive, winter-annual habit in Arabidopsis.
AB  - The winter-annual habit (which typically involves a requirement for exposure to
      the cold of winter to flower in the spring) in Arabidopsis thaliana is mainly due
      to the repression of flowering by relatively high levels of FLC expression.
      Exposure to prolonged cold attenuates FLC expression through a process known as
      vernalization and thus permits flowering to occur in the spring. Here we show
      that the elevated FLC expression characteristic of nonvernalized winter annuals
      requires two genes, EARLY FLOWERING 7 (ELF7) and EARLY FLOWERING 8 (ELF8), that
      are homologs of components of the PAF1 complex of Saccharomyces cerevisiae.
      Furthermore, ELF7 and ELF8 are also required for the expression of other genes in
      the FLC clade of flowering repressors such as MAF2 and FLM. FLC, FLM, and MAF2
      are involved in multiple flowering pathways that account for the broad effects of
      elf7 and elf8 mutations on flowering behavior. ELF7 and ELF8 are required for the
      enhancement of histone 3 trimethylation at Lys 4 in FLC chromatin. This
      modification of FLC chromatin appears to be required to elevate FLC expression to
      levels that can delay flowering in plants that have not been vernalized. A model
      of the role of ELF7, ELF8, and other previously described genes in the
      modification of the chromatin of flowering repressors is presented.

PMID- 15520274
TI  - Mitochondrial fission proteins regulate programmed cell death in yeast.
AB  - The possibility that single-cell organisms undergo programmed cell death has been
      questioned in part because they lack several key components of the mammalian cell
      death machinery. However, yeast encode a homolog of human Drp1, a mitochondrial
      fission protein that was shown previously to promote mammalian cell death and the
      excessive mitochondrial fragmentation characteristic of apoptotic mammalian
      cells. In support of a primordial origin of programmed cell death involving
      mitochondria, we found that the Saccharomyces cerevisiae homolog of human Drp1,
      Dnm1, promotes mitochondrial fragmentation/degradation and cell death following
      treatment with several death stimuli. Two Dnm1-interacting factors also regulate
      yeast cell death. The WD40 repeat protein Mdv1/Net2 promotes cell death,
      consistent with its role in mitochondrial fission. In contrast to its fission
      function in healthy cells, Fis1 unexpectedly inhibits Dnm1-mediated mitochondrial
      fission and cysteine protease-dependent cell death in yeast. Furthermore, the
      ability of yeast Fis1 to inhibit mitochondrial fission and cell death can be
      functionally replaced by human Bcl-2 and Bcl-xL. Together, these findings
      indicate that yeast and mammalian cells have a conserved programmed death pathway
      regulated by a common molecular component, Drp1/Dnm1, that is inhibited by a Bcl
      2-like function.

PMID- 15520275
TI  - Idling by DNA polymerase delta maintains a ligatable nick during lagging-strand
      DNA replication.
AB  - During each yeast cell cycle, approximately 100,000 nicks are generated during
      lagging-strand DNA replication. Efficient nick processing during Okazaki fragment
      maturation requires the coordinated action of DNA polymerase delta (Pol delta)
      and the FLAP endonuclease FEN1. Misregulation of this process leads to the
      accumulation of double-stranded breaks and cell lethality. Our studies highlight
      a remarkably efficient mechanism for Okazaki fragment maturation in which Pol
      delta by default displaces 2-3 nt of any downstream RNA or DNA it encounters. In
      the presence of FEN1, efficient nick translation ensues, whereby a mixture of
      mono- and small oligonucleotides are released. If FEN1 is absent or not optimally
      functional, the ability of Pol delta to back up via its 3'-5'-exonuclease
      activity, a process called idling, maintains the polymerase at a position that is
      ideal either for ligation (in case of a DNA-DNA nick) or for subsequent
      engagement by FEN1 (in case of a DNA-RNA nick). Consistent with the hypothesis
      that DNA polymerase epsilon is the leading-strand enzyme, we observed no idling
      by this enzyme and no cooperation with FEN1 for creating a ligatable nick.

PMID- 15520276
TI  - Increased gene dosage of Ink4a/Arf results in cancer resistance and normal aging.
AB  - Mammalian genes frequently present allelic variants that differ in their
      expression levels and that, in the case of tumor suppressor genes, can be of
      relevance for cancer susceptibility and aging. We report here the
      characterization of a novel mouse model with increased activity for the Ink4a and
      Arf tumor suppressors. We have generated a "super Ink4a/Arf" mouse strain
      carrying a transgenic copy of the entire Ink4a/Arf locus. Cells derived from
      super Ink4a/Arf mice have increased resistance to in vitro immortalization and
      oncogenic transformation. Importantly, super Ink4a/Arf mice manifest higher
      resistance to cancer compared to normal, nontransgenic, mice. Finally, super
      Ink4a/Arf mice have normal aging and lifespan. Together, these results indicate
      that modest increases in the activity of the Ink4a/Arf tumor suppressor result in
      a beneficial cancer-resistant phenotype without affecting normal viability or
      aging.

PMID- 15520278
TI  - At the interface between signaling and executing anaphase--Cdc14 and the FEAR
      network.
AB  - Anaphase is the stage of the cell cycle when the duplicated genome is separated
      to opposite poles of the cell. The irreversible nature of this event confers a
      unique burden on the cell and it is therefore not surprising that the regulation
      of this cell cycle stage is complex. In budding yeast, a signaling network known
      as the Cdc fourteen early anaphase release (FEAR) network and its effector, the
      protein phosphatase Cdc14, play a key role in the coordination of the multiple
      events that occur during anaphase, such as partitioning of the DNA, regulation of
      spindle stability, activation of microtubule forces, and initiation of mitotic
      exit. These functions of the FEAR network contribute to genomic stability by
      coordinating the completion of anaphase and the execution of mitotic exit.

PMID- 15520277
TI  - Systematic analysis and nomenclature of mammalian F-box proteins.

PMID- 15520279
TI  - YY1 DNA binding and PcG recruitment requires CtBP.
AB  - We found that mammalian Polycomb group (PcG) protein YY1 can bind to Polycomb
      response elements in Drosophila embryos and can recruit other PcG proteins to
      DNA. PcG recruitment results in deacetylation and methylation of histone H3. In a
      CtBP mutant background, recruitment of PcG proteins and concomitant histone
      modifications do not occur. Surprisingly, YY1 DNA binding in vivo is also
      ablated. CtBP mutation does not result in YY1 degradation or transport from the
      nucleus, suggesting a mechanism whereby YY1 DNA binding ability is masked. These
      results reveal a new role for CtBP in controlling YY1 DNA binding and recruitment
      of PcG proteins to DNA.

PMID- 15520280
TI  - Skp2-dependent degradation of p27kip1 is essential for cell cycle progression.
AB  - The activity of the SCF(skp2) E3 ligase is required for the proteolytic turnover
      of several proteins involved in cell cycle control and transcriptional
      regulation. Loss of skp2 in the mouse leads to a complex phenotype including
      changes in cell size and DNA content as well as severe proliferation defects.
      Here we show that the loss of a single skp2 substrate, namely, the cyclin kinase
      inhibitor p27kip1, reverts the phenotype of skp2 knockout hepatocytes to normal.
      By comparing the kinetics of p27 turnover and cell cycle progression in skp2
      knockout and p27T187A knock-in mice, we define a short period in G1 in which p27
      is able to block the cell cycle after the exit from quiescence. Loss of p27
      turnover during this period prevents mitotic division and instead leads to
      compensatory cell growth.

PMID- 15520281
TI  - Pax3:Fkhr interferes with embryonic Pax3 and Pax7 function: implications for
      alveolar rhabdomyosarcoma cell of origin.
AB  - To investigate the role of the translocation-associated gene Pax3:Fkhr in
      alveolar rhabdomyosarcomas, we generated a Cre-mediated conditional knock-in of
      Pax3:Fkhr into the mouse Pax3 locus. Exploring embryonic tumor cell origins, we
      replaced a Pax3 allele with Pax3:Fkhr throughout its expression domain, causing
      dominant-negative effects on Pax3 and paradoxical activation of the Pax3 target
      gene, c-Met. Ectopic neuroprogenitor cell proliferation also occurs. In contrast,
      activation later in embryogenesis in cells that express Pax7 results in viable
      animals with a postnatal growth defect and a moderately decreased Pax7+ muscle
      satellite cell pool, phenocopying Pax7 deficiency but remarkably not leading to
      tumors.

PMID- 15520282
TI  - The Polycomb Ezh2 methyltransferase regulates muscle gene expression and skeletal
      muscle differentiation.
AB  - The Ezh2 protein endows the Polycomb PRC2 and PRC3 complexes with histone lysine
      methyltransferase (HKMT) activity that is associated with transcriptional
      repression. We report that Ezh2 expression was developmentally regulated in the
      myotome compartment of mouse somites and that its down-regulation coincided with
      activation of muscle gene expression and differentiation of satellite-cell
      derived myoblasts. Increased Ezh2 expression inhibited muscle differentiation,
      and this property was conferred by its SET domain, required for the HKMT
      activity. In undifferentiated myoblasts, endogenous Ezh2 was associated with the
      transcriptional regulator YY1. Both Ezh2 and YY1 were detected, with the
      deacetylase HDAC1, at genomic regions of silent muscle-specific genes. Their
      presence correlated with methylation of K27 of histone H3. YY1 was required for
      Ezh2 binding because RNA interference of YY1 abrogated chromatin recruitment of
      Ezh2 and prevented H3-K27 methylation. Upon gene activation, Ezh2, HDAC1, and YY1
      dissociated from muscle loci, H3-K27 became hypomethylated and MyoD and SRF were
      recruited to the chromatin. These findings suggest the existence of a two-step
      activation mechanism whereby removal of H3-K27 methylation, conferred by an
      active Ezh2-containing protein complex, followed by recruitment of positive
      transcriptional regulators at discrete genomic loci are required to promote
      muscle gene expression and cell differentiation.

PMID- 15520283
TI  - The Promoter Targeting Sequence mediates epigenetically heritable transcription
      memory.
AB  - Large gene complexes frequently use "specialized" DNA elements to ensure proper
      regulation of gene activities. The Promoter Targeting Sequence (PTS) from the
      Abdominal-B locus of the Drosophila Bithorax complex overcomes an insulator, and
      facilitates, yet restricts, distant enhancers to a single promoter. We found that
      this promoter-targeting activity is independent of an enhancer's tissue or
      temporal specificity, and can be remembered in all somatic cells in the absence
      of promoter activation. It requires an insulator for its establishment, but can
      be maintained by the PTS in the absence of an insulator. More importantly, the
      promoter-targeting activity can be remembered after the transgene is translocated
      to new chromosomal locations. These results suggest that promoter targeting is
      established independent of enhancer activity, and is maintained epigenetically
      throughout development and subsequent generations.

PMID- 15520284
TI  - Rapid accumulation of mutations during seed-to-seed propagation of mismatch
      repair-defective Arabidopsis.
AB  - During the many cell divisions that precede formation of plant gametes, their
      apical-meristem and floral antecedents are continually exposed to endogenous and
      environmental mutagenic threats. Although some deleterious recessive mutations
      may be eliminated during growth of haploid gametophytes and functionally haploid
      early embryos ("haplosufficiency quality-checking"), the multiplicity of plant
      genome-maintenance systems suggests aggressive quality control during prior
      diploid growth. To test in Arabidopsis a hypothesis that prior mismatch repair
      (MMR) is paramount in defense of plant genetic fidelity, we propagated in
      parallel 36 MMR-defective (Atmsh2-1) and 36 wild-type lines. The Atmsh2-1 lines
      rapidly accumulated a wide variety of mutations: fifth-generation (G5) plants
      showed abnormalities in morphology and development, fertility, germination
      efficiency, seed/silique development, and seed set. Only two Atmsh2-1, but all 36
      wild-type lines, appeared normal at G5. Analyses of insertion/deletion mutation
      at six repeat-sequence (microsatellite) loci showed each Atmsh2-1 line to have
      evolved its own "fingerprint," the results of as many as 10 microsatellite
      mutations in a single line. Thus, MMR during diploid growth is essential for
      plant genomic integrity.

PMID- 15520285
TI  - Fine-tuning of the Escherichia coli sigmaE envelope stress response relies on
      multiple mechanisms to inhibit signal-independent proteolysis of the
      transmembrane anti-sigma factor, RseA.
AB  - Proteolytic cascades are widely implicated in signaling between cellular
      compartments. In Escherichia coli, accumulation of unassembled outer membrane
      porins (OMPs) in the envelope leads to expression of sigma(E)-dependent genes in
      the cytoplasmic cellular compartment. A proteolytic cascade conveys the OMP
      signal by regulated proteolysis of RseA, a membrane-spanning anti-sigma factor
      whose cytoplasmic domain inhibits sigma(E)-dependent transcription. Upon
      activation by OMP C termini, the membrane localized DegS protease cleaves RseA in
      its periplasmic domain, the membrane-embedded protease RseP (YaeL) cleaves RseA
      near the inner membrane, and the released cytoplasmic RseA fragment is further
      degraded. Initiation of RseA degradation by activated DegS makes the system
      sensitive to a wide range of OMP concentrations and unresponsive to variations in
      the levels of DegS and RseP proteases. These features rely on the inability of
      RseP to cleave intact RseA. In the present report, we demonstrate that RseB,
      which binds to the periplasmic face of RseA, and DegS each independently inhibits
      RseP cleavage of intact RseA. Thus, the function of RseB, widely conserved among
      bacteria using the sigma(E) pathway, and the second role of DegS (in addition to
      RseA proteolysis initiation) is to improve the performance characteristics of
      this signal transduction system.

PMID- 15520286
TI  - Serial segmental duplications during primate evolution result in complex human
      genome architecture.
AB  - The human genome is particularly rich in low-copy repeats (LCRs) or segmental
      duplications (5%-10%), and this characteristic likely distinguishes us from lower
      mammals such as rodents. How and why the complex human genome architecture
      consisting of multiple LCRs has evolved remains an open question. Using molecular
      and computational analyses of human and primate genomic regions, we analyzed the
      structure and evolution of LCRs that resulted in complex architectural features
      of the human genome in proximal 17p. We found that multiple LCRs of different
      origins are situated adjacent to one another, whereas each LCR changed at
      different time points between >25 to 3-7 million years ago (Mya) during primate
      evolution. Evolutionary studies in primates suggested communication between the
      LCRs by gene conversion. The DNA transposable element MER1-Charlie3 and
      retroviral ERVL elements were identified at the breakpoint of the t(4;19)
      chromosome translocation in Gorilla gorilla, suggesting a potential role for
      transpositions in evolution of the primate genome. Thus, a series of consecutive
      segmental duplication events during primate evolution resulted in complex genome
      architecture in proximal 17p. Some of the more recent events led to the formation
      of novel genes that in human are expressed primarily in the brain. Our
      observations support the contention that serial segmental duplication events
      might have orchestrated primate evolution by the generation of novel
      fusion/fission genes as well as potentially by genomic inversions associated with
      decreased recombination rates facilitating gene divergence.

PMID- 15520287
TI  - Genome sequence of Haloarcula marismortui: a halophilic archaeon from the Dead
      Sea.
AB  - We report the complete sequence of the 4,274,642-bp genome of Haloarcula
      marismortui, a halophilic archaeal isolate from the Dead Sea. The genome is
      organized into nine circular replicons of varying G+C compositions ranging from
      54% to 62%. Comparison of the genome architectures of Halobacterium sp. NRC-1 and
      H. marismortui suggests a common ancestor for the two organisms and a genome of
      significantly reduced size in the former. Both of these halophilic archaea use
      the same strategy of high surface negative charge of folded proteins as means to
      circumvent the salting-out phenomenon in a hypersaline cytoplasm. A multitiered
      annotation approach, including primary sequence similarities, protein family
      signatures, structure prediction, and a protein function association network, has
      assigned putative functions for at least 58% of the 4242 predicted proteins, a
      far larger number than is usually achieved in most newly sequenced
      microorganisms. Among these assigned functions were genes encoding six opsins, 19
      MCP and/or HAMP domain signal transducers, and an unusually large number of
      environmental response regulators-nearly five times as many as those encoded in
      Halobacterium sp. NRC-1--suggesting H. marismortui is significantly more
      physiologically capable of exploiting diverse environments. In comparing the
      physiologies of the two halophilic archaea, in addition to the expected extensive
      similarity, we discovered several differences in their metabolic strategies and
      physiological responses such as distinct pathways for arginine breakdown in each
      halophile. Finally, as expected from the larger genome, H. marismortui encodes
      many more functions and seems to have fewer nutritional requirements for survival
      than does Halobacterium sp. NRC-1.

PMID- 15520288
TI  - Whole-genome analysis of Alu repeat elements reveals complex evolutionary
      history.
AB  - Alu repeats are the most abundant family of repeats in the human genome, with
      over 1 million copies comprising 10% of the genome. They have been implicated in
      human genetic disease and in the enrichment of gene-rich segmental duplications
      in the human genome, and they form a rich fossil record of primate and human
      history. Alu repeat elements are believed to have arisen from the replication of
      a small number of source elements, whose evolution over time gives rise to the 31
      Alu subfamilies currently reported in Repbase Update. We apply a novel method to
      identify and statistically validate 213 Alu subfamilies. We build an evolutionary
      tree of these subfamilies and conclude that the history of Alu evolution is more
      complex than previous studies had indicated.

PMID- 15520290
TI  - Properties of overlapping genes are conserved across microbial genomes.
AB  - There are numerous examples from the genomes of viruses, mitochondria, and
      chromosomes that adjacent genes can overlap, sharing at least one nucleotide.
      Overlaps have been hypothesized to be involved in genome size minimization and as
      a regulatory mechanism of gene expression. Here we show that overlapping genes
      are a consistent feature (approximately one-third of all genes) across all
      microbial genomes sequenced to date, have homologs in more microbes than do non
      overlapping genes, and are therefore likely more conserved. In addition, the
      size, phase (reading frame offset), and distribution, among other
      characteristics, of overlapping genes are most consistent with the hypothesis
      that overlaps function in the regulation of gene expression. The upstream
      sequences and conservation of overlapping orthologs of two model organisms from
      the genus Prochlorococcus that have significantly different GC-content, and
      therefore different nucleotide sequences for orthologs, are also consistent with
      small overlapping sequence regions and programmed shifts in reading frame as a
      common mechanism in the regulation of microbial gene expression.

PMID- 15520289
TI  - The human L1 promoter: variable transcription initiation sites and a major impact
      of upstream flanking sequence on promoter activity.
AB  - Human L1 elements are non-LTR retrotransposons that comprise approximately 17% of
      the human genome. Their 5'-untranslated region (5'-UTR) serves as a promoter for
      L1 transcription. Now we find that transcription initiation sites are not
      restricted to nucleotide +1 but vary considerably in both downstream and upstream
      directions. Transcription initiating upstream explains additional nucleotides
      often seen between the 5'-target site duplication and the L1 start site. A higher
      frequency of G nucleotides observed upstream from the L1 can be explained by
      reverse transcription of the L1 RNA 5'-CAP, which is further supported by extra
      Gs seen for full-length HERV-W pseudogenes. We assayed 5'-UTR promoter activities
      for several full-length human L1 elements, and found that upstream flanking
      cellular sequences strongly influence the L1 5'-UTR promoter. These sequences
      either repress or enhance the L1 promoter activity. Therefore, the evolutionary
      success of a human L1 in producing progeny depends not only on the L1 itself, but
      also on its genomic integration site. The promoter mechanism of L1 is reminiscent
      of initiator (Inr) elements that are TATA-less promoters expressing several
      cellular genes. We suggest that the L1 5'-UTR is able to form an Inr element that
      reaches into upstream flanking sequence.

PMID- 15520291
TI  - The molecular structure of the DNA fragments eliminated during chromatin
      diminution in Cyclops kolensis.
AB  - Presumptive somatic cells of the copepod Cyclops kolensis specifically eliminate
      a large fraction of their genome by the process of chromatin diminution. The
      eliminated DNA (eDNA) remains only in the germline cells. Very little is known
      about the nature of the sequences eliminated from somatic cells. We cloned a
      fraction of the eDNA and sequenced 90 clones that total 32 kb. The following
      organizational patterns were demonstrated for the eDNA sequences. All do not
      contain open reading frames. Each fragment contains 1-3 families of short repeats
      (10-30 bp) highly homologous within families (87%-100%). Most repeats are
      separated by spacers up to 50 bp long. Homologous regions were found between
      fragments, motifs from 15-300 bp in length. Among fragments there occur groups in
      which the same motifs are ordered in the same fashion. However, spacers between
      the motifs differ in length and nucleotide composition. Ubiquitous motifs (those
      occurring in all fragments) were identified. Analysis of motifs revealed
      submotifs, each occurring within several motifs. Thus, motifs may be regarded as
      mosaic structures composed of submotifs (short repeats). Taken together, the
      results provide evidence of a high organizational ordering of the DNA sequences
      restricted to the germline. With this in mind, it appears incorrect to refer to
      this part of the genome as junk. Moreover, eDNA is redundant for only the somatic
      cells-its function is to be sought in germline cells.

PMID- 15520292
TI  - Patterns of large-scale genomic variation in virulent and avirulent Burkholderia
      species.
AB  - The human diseases melioidosis and glanders are caused by the bacteria
      Burkholderia pseudomallei and B. mallei respectively, and both species are
      regarded as potential biowarfare agents. We used B. pseudomallei DNA microarrays
      to compare the genomes of several clinical and environmental isolates of B.
      pseudomallei, B. mallei, and B. thailandensis, a closely related but avirulent
      species. Open reading frames (ORFs) deleted between the three species were
      associated with diverse cellular functions, including nitrogen and iron
      metabolism, quorum sensing, and polysaccharide production. Deleted ORFs in B.
      mallei exhibited significant genomic clustering, whereas deletions in B.
      thailandensis were more uniformly dispersed, suggesting that B. mallei and B.
      thailandensis may have diverged from B. pseudomallei and each other via distinct
      mechanisms. The genomes of independent B. pseudomallei isolates were highly
      conserved with a large-scale variance of less than 3% between isolates, and at
      least three distinct molecular subtypes could be defined. An analysis of subtype
      specific genomic regions suggests that DNA loss has played an important role in
      the evolutionary radiation of B. pseudomallei in the natural environment. Our
      results raise several hypotheses concerning the possible mechanisms underlying
      the diverse biological properties exhibited by members of the Burkholderia
      family.

PMID- 15520293
TI  - Global analysis of transcript and protein levels across the Plasmodium falciparum
      life cycle.
AB  - To investigate the role of post-transcriptional controls in the regulation of
      protein expression for the malaria parasite, Plasmodium falciparum, we have
      compared mRNA transcript and protein abundance levels for seven different stages
      of the parasite life cycle. A moderately high positive relationship between mRNA
      and protein abundance was observed for these stages; the most common discrepancy
      was a delay between mRNA and protein accumulation. Potentially post
      transcriptionally regulated genes are identified, and families of functionally
      related genes were observed to share similar patterns of mRNA and protein
      accumulation.

PMID- 15520294
TI  - Isolation of the repertoire of VSG expression site containing telomeres of
      Trypanosoma brucei 427 using transformation-associated recombination in yeast.
AB  - Trypanosoma brucei switches between variant surface glycoproteins (VSGs) allowing
      immune escape. The active VSG is in one of many telomeric bloodstream form VSG
      expression sites (BESs), also containing expression site-associated genes (ESAGs)
      involved in host adaptation. The role of BES sequence diversity in parasite
      virulence can best be understood through analysis of the full repertoire of BESs
      from a given T. brucei strain. However, few BESs have been cloned, as telomeres
      are highly underrepresented in standard libraries. We devised a strategy for
      isolating the repertoire of T. brucei 427 BES-containing telomeres in
      Saccaromyces cerevisiae by using transformation-associated recombination (TAR).
      We isolated 182 T. brucei 427 BES TAR clones, 167 of which could be subdivided
      into minimally 17 BES groups. This set gives us the first view of the breadth and
      diversity of BESs from one T. brucei strain. Most BESs ranged between 40 and 70
      kb (average, 57 +/- 17 kb) and contained most identified ESAGs. Phylogenetic
      comparison of the cohort of BES promoter and ESAG6 sequences did not show similar
      trees, indicating rapid evolution most likely mediated by sequence exchange
      between BESs. This cloning strategy could be used for any T. brucei strain,
      facilitating research on the biodiversity of telomeric gene families and host
      pathogen interactions.

PMID- 15520295
TI  - A novel method for multiple alignment of sequences with repeated and shuffled
      elements.
AB  - We describe ABA (A-Bruijn alignment), a new method for multiple alignment of
      biological sequences. The major difference between ABA and existing multiple
      alignment methods is that ABA represents an alignment as a directed graph,
      possibly containing cycles. This representation provides more flexibility than
      does a traditional alignment matrix or the recently introduced partial order
      alignment (POA) graph by allowing a larger class of evolutionary relationships
      between the aligned sequences. Our graph representation is particularly well
      suited to the alignment of protein sequences with shuffled and/or repeated domain
      structure, and allows one to construct multiple alignments of proteins containing
      (1) domains that are not present in all proteins, (2) domains that are present in
      different orders in different proteins, and (3) domains that are present in
      multiple copies in some proteins. In addition, ABA is useful in the alignment of
      genomic sequences that contain duplications and inversions. We provide several
      examples illustrating the applications of ABA.

PMID- 15520296
TI  - A novel, high-performance random array platform for quantitative gene expression
      profiling.
AB  - We have developed a new microarray technology for quantitative gene-expression
      profiling on the basis of randomly assembled arrays of beads. Each bead carries a
      gene-specific probe sequence. There are multiple copies of each sequence-specific
      bead in an array, which contributes to measurement precision and reliability. We
      optimized the system for specific and sensitive analysis of mammalian RNA, and
      using RNA controls of defined concentration, obtained the following estimates of
      system performance: specificity of 1:250,000 in mammalian poly(A(+)) mRNA; limit
      of detection 0.13 pM; dynamic range 3.2 logs; and sufficient precision to detect
      1.3-fold differences with 95% confidence within the dynamic range. Measurements
      of expression differences between human brain and liver were validated by
      concordance with quantitative real-time PCR (R(2) = 0.98 for log-transformed
      ratios, and slope of the best-fit line = 1.04, for 20 genes). Quantitative
      performance was further verified using a mouse B- and T-cell model system. We
      found published reports of B- or T-cell-specific expression for 42 of 59 genes
      that showed the greatest differential expression between B- and T-cells in our
      system. All of the literature observations were concordant with our results. Our
      experiments were carried out on a 96-array matrix system that requires only 100
      ng of input RNA and uses standard microtiter plates to process samples in
      parallel. Our technology has advantages for analyzing multiple samples, is
      scalable to all known genes in a genome, and is flexible, allowing the use of
      standard or custom probes in an array.

PMID- 15520297
TI  - DNA amplification method tolerant to sample degradation.
AB  - Despite recent advances in linear whole genome amplification of intact DNA/RNA,
      amplification of degraded nucleic acids in an unbiased fashion remains a serious
      challenge for genetic diagnosis. We describe a new whole genome amplification
      procedure, RCA-RCA (Restriction and Circularization-Aided Rolling Circle
      Amplification), which retains the allelic differences among degraded amplified
      genomes while achieving almost complete genome coverage. RCA-RCA utilizes
      restriction digestion and whole genome circularization to generate genomic
      sequences amenable to rolling circle amplification. When intact genomic DNA is
      used, RCA-RCA retains gene-amplification differences (twofold or higher) between
      complex genomes on a genome-wide scale providing highly improved concordance with
      unamplified material as compared with other amplification methodologies including
      multiple displacement amplification. Using RCA-RCA, formalin-fixed samples of
      modest or substantial DNA degradation were successfully amplified and screened
      via array-CGH or Taqman PCR that displayed retention of the principal gene
      amplification features of the original material. Microsatellite analysis revealed
      that RCA-RCA amplified genomic DNA is representative of the original material at
      the nucleotide level. Amplification of cDNA is successfully performed via RCA-RCA
      and results to unbiased gene expression analysis (R(2) = 0.99). The simplicity
      and universal applicability of RCA-RCA make it a powerful new tool for genome
      analysis with unique advantages over previous amplification technologies.

PMID- 15520298
TI  - OptStrain: a computational framework for redesign of microbial production
      systems.
AB  - This paper introduces the hierarchical computational framework OptStrain aimed at
      guiding pathway modifications, through reaction additions and deletions, of
      microbial networks for the overproduction of targeted compounds. These compounds
      may range from electrons or hydrogen in biofuel cell and environmental
      applications to complex drug precursor molecules. A comprehensive database of
      biotransformations, referred to as the Universal database (with >5700 reactions),
      is compiled and regularly updated by downloading and curating reactions from
      multiple biopathway database sources. Combinatorial optimization is then used to
      elucidate the set(s) of non-native functionalities, extracted from this Universal
      database, to add to the examined production host for enabling the desired product
      formation. Subsequently, competing functionalities that divert flux away from the
      targeted product are identified and removed to ensure higher product yields
      coupled with growth. This work represents an advancement over earlier efforts by
      establishing an integrated computational framework capable of constructing
      stoichiometrically balanced pathways, imposing maximum product yield
      requirements, pinpointing the optimal substrate(s), and evaluating different
      microbial hosts. The range and utility of OptStrain are demonstrated by
      addressing two very different product molecules. The hydrogen case study
      pinpoints reaction elimination strategies for improving hydrogen yields using two
      different substrates for three separate production hosts. In contrast, the
      vanillin study primarily showcases which non-native pathways need to be added
      into Escherichia coli. In summary, OptStrain provides a useful tool to aid
      microbial strain design and, more importantly, it establishes an integrated
      framework to accommodate future modeling developments.

PMID- 15520299
TI  - Osteopontin: a protective mediator of cardiac fibrosis?

PMID- 15520300
TI  - Blunted decline in systolic blood pressure after exercise predicts future acute
      myocardial infarction.

PMID- 15520301
TI  - Early life factors and blood pressure at age 31 years in the 1966 northern
      Finland birth cohort.
AB  - Data on the birth weight-blood pressure relationship are inconsistent. Although
      an inverse association has been suggested in several large studies,
      interpretation is complicated by publication and other biases. Few data are
      available on the relationship between other early growth measures and blood
      pressure. We examined the shape and size of association between determinants of
      fetal growth, size at birth, growth in infancy, and adult systolic and diastolic
      blood pressure at 31 years in the prospective northern Finnish 1966 birth cohort
      of 5960 participants. Birth weight, birth length, gestational age, ponderal
      index, and birth weight relative to gestational age showed a significant inverse
      association with blood pressure at age 31. Rapid growth in infancy ("change-up")
      was positively associated with blood pressure. Adjusted regression coefficients
      for birth weight indicated systolic/diastolic blood pressure lower by -1.7 (95%
      confidence interval [CI], -2.5, -1.0)/-0.7 (95% CI, -1.4, -0.02) mm Hg for 1 kg
      higher birth weight. The significant inverse association between birth weight and
      systolic blood pressure persisted without adjustment for adult body mass index
      for males. Among females, gestational age showed a stronger association with
      blood pressure than birth weight: gestational age higher by 7 weeks (equivalent
      to an average of 1 kg higher birth weight) among singletons associated with -2.9
      (95% CI, -4.7, -1.1) mm Hg lower systolic blood pressure. Our results support the
      concept that birth weight, other birth measures, and infant growth are important
      determinants of blood pressure and hence cardiovascular disease risk in later
      life.

PMID- 15520302
TI  - Hypertension and RhoA/Rho-kinase signaling in the vasculature: highlights from
      the recent literature.
AB  - Under normal conditions, contractile activity in vascular smooth muscle is
      initiated by either receptor activation (norepinephrine, angiotensin II, etc.) or
      by a stretch-activated mechanism. After this activation, several signaling
      pathways can initiate a Ca2+-calmodulin interaction to stimulate phosphorylation
      of the light chain of myosin. Ca2+ sensitization of the contractile proteins is
      signaled by the RhoA/Rho-kinase pathway to inhibit the dephosphorylation of the
      light chain by myosin phosphatase thereby maintaining force generation. In
      opposition to force generation, NO is released from endothelial cells and causes
      vasodilation through inhibition of the RhoA/Rho-kinase signaling pathway. This
      brief review will highlight recent studies demonstrating a role for the RhoA/Rho
      kinase signaling pathway in the increased vasoconstriction characteristic of
      hypertension.

PMID- 15520303
TI  - Sympathetic neural activation in nondiabetic metabolic syndrome and its further
      augmentation by hypertension.
AB  - Hypertension is a major cardiovascular risk factor in the metabolic syndrome (MS)
      in which the presence of insulin resistance, glucose intolerance, abnormal
      lipoprotein metabolism, and central obesity all confer an increased risk. Because
      essential hypertension (EHT), insulinemia, and visceral fat are associated with
      sympathetic hyperactivity, which is itself known to increase cardiovascular risk,
      the aim of this study was to see if MS is a state of sympathetic nerve
      hyperactivity and if the additional presence of EHT intensifies this
      hyperactivity. In 69 closely matched subjects, comprising hypertensive MS
      (MS+EHT, 18), normotensive MS (MS-EHT, 17), hypertensives without MS (EHT, 16),
      and normotensive controls without MS (NC, 18), we measured resting muscle
      sympathetic nerve activity (MSNA) as assessed from multiunit discharges and from
      single units with defined vasoconstrictor properties (s-MSNA). The s-MSNA in
      MS+EHT (76+/-3.1 impulses/100 beats) was greater (at least P<0.01) than in MS-EHT
      (62+/-3.2 impulses/100 beats) and in EHT (60+/-2.3 impulses/100 beats), and all
      these were significantly greater (at least P<0.01) than in NC (46+/-2.7
      impulse/100 beats). The multi-unit MSNA followed a similar trend. These findings
      suggest that MS is a state of sympathetic nerve hyperactivity and that the
      additional presence of hypertension further intensifies this hyperactivity. The
      degree of sympathetic hyperactivity seen in this study could be argued at least
      partly to contribute to the higher cardiovascular risk and metabolic
      abnormalities seen in MS+EHT patients.

PMID- 15520304
TI  - Extracorporeal cardiac shock wave therapy markedly ameliorates ischemia-induced
      myocardial dysfunction in pigs in vivo.
AB  - BACKGROUND: Prognosis of ischemic cardiomyopathy still remains poor because of
      the lack of effective treatments. To develop a noninvasive therapy for the
      disorder, we examined the in vitro and vivo effects of extracorporeal shock wave
      (SW) that could enhance angiogenesis. METHODS AND RESULTS: SW treatment applied
      to cultured human umbilical vein endothelial cells significantly upregulated mRNA
      expression of vascular endothelial growth factor and its receptor Flt-1 in vitro.
      A porcine model of chronic myocardial ischemia was made by placing an ameroid
      constrictor at the proximal segment of the left circumflex coronary artery, which
      gradually induced a total occlusion of the artery with sustained myocardial
      dysfunction but without myocardial infarction in 4 weeks. Thereafter,
      extracorporeal SW therapy to the ischemic myocardial region (200 shots/spot for 9
      spots at 0.09 mJ/mm2) was performed (n=8), which induced a complete recovery of
      left ventricular ejection fraction (51+/-2% to 62+/-2%), wall thickening fraction
      (13+/-3% to 30+/-3%), and regional myocardial blood flow (1.0+/-0.2 to 1.4+/-0.3
      mL x min(-1) x g(-1)) of the ischemic region in 4 weeks (all P<0.01). By
      contrast, animals that did not receive the therapy (n=8) had sustained myocardial
      dysfunction (left ventricular ejection fraction, 48+/-3% to 48+/-1%; wall
      thickening fraction, 13+/-2% to 9+/-2%) and regional myocardial blood flow (1.0+/
      0.3 to 0.6+/-0.1 mL x min(-1) x g(-1)). Neither arrhythmias nor other
      complications were observed during or after the treatment. SW treatment of the
      ischemic myocardium significantly upregulated vascular endothelial growth factor
      expression in vivo. CONCLUSIONS: These results suggest that extracorporeal
      cardiac SW therapy is an effective and noninvasive therapeutic strategy for
      ischemic heart disease.

PMID- 15520305
TI  - Epicardial mapping of chronic atrial fibrillation in patients: preliminary
      observations.
AB  - BACKGROUND: The mechanisms of chronic atrial fibrillation (AF) are not well
      understood. We performed epicardial mapping of chronic AF in patients undergoing
      open heart surgery to test the hypothesis that chronic AF is due to a left atrial
      "driver" with a regular, short cycle length, resulting in fibrillatory conduction
      to the rest of the atria. METHODS AND RESULTS: Nine patients with chronic AF (1
      month to >15 years' duration) were studied at open heart surgery, 8 before and 1
      during cardiopulmonary bypass. During AF, atrial electrograms (AEGs) were
      recorded for 1 to 5 minutes from 404 epicardial electrodes arranged in bipoles
      along with ECG lead II or ventricular electrogram. Four-second segments of each
      bipolar AEG were also subjected to fast Fourier transform analysis. Two patterns
      of atrial activation were present during AF. In pattern 1 (7/9 patients), AEGs
      from parts of the atria demonstrated a short, regular cycle length with identical
      beat-to-beat morphology, and the rest of the atria were activated irregularly,
      and AEGs that demonstrated constant morphology and cycle length were localized to
      parts of the left atria (5/7), the right atria (1/7), or both atria (1/7). In
      pattern 2 (2/9 patients), AEGs showed no evidence of regular activation or
      constant morphology. CONCLUSIONS: In 9 patients with chronic AF, the commonest
      recorded AEG pattern showed an area of regular, rapid rhythm, consistent with the
      possibility that a driver causing fibrillatory conduction is one mechanism of AF
      in these patients.

PMID- 15520306
TI  - Gelatin hydrogel microspheres enable pinpoint delivery of basic fibroblast growth
      factor for the development of functional collateral vessels.
AB  - BACKGROUND: Various growth factors promote collateral vessel development and are
      regarded as promising for the treatment of vascular occlusive diseases. However,
      an efficacious delivery system for them has yet to be established. We devised a
      strategy to augment functional collateral vessels by using acidic gelatin
      hydrogel microspheres (AGHMs) incorporating basic fibroblast growth factor
      (bFGF). The aim of the present study was to investigate the hypothesis that by
      intra-arterial (IA) administration of bFGF-impregnated AGHMs, bFGF could be
      delivered from AGHMs trapped in distal small-diameter vessels and thereby induce
      functional collateral vessels with an assured blood supply through the process of
      arteriogenesis. METHODS AND RESULTS: Various sizes of AGHMs (3 mg) incorporating
      125I-labeled bFGF were injected into the left internal iliac artery of a rabbit
      model of hindlimb ischemia. Less than 50% of radioactivity accumulated in the
      ischemic hindlimb after injection of AGHMs that were 10 mum in diameter, whereas
      approximately 80% of radioactivity was counted in the ischemic limb after
      administration of 29- or 59-microm-diameter AGHMs. Calf blood pressure ratio and
      the ratio of regional blood flow of the bilateral hindlimbs immediately before
      and after IA administration of 29-microm-diameter AGHMs showed no significant
      change. Then we evaluated the function of the developed collateral vessels 28
      days after IA administration of bFGF-impregnated, 29-microm-diameter AGHMs. IA
      administration of bFGF-impregnated AGHMs induced marked collateral vessel
      improvement compared with IA administration of phosphate buffered saline-treated
      AGHMs and intramuscular administration of bFGF-impregnated AGHMs. CONCLUSIONS: IA
      administration of bFGF-impregnated, 29-microm-diameter AGHMs strongly induced
      functional collateral vessels without worsening ischemia, indicating the possible
      therapeutic usefulness of this approach.

PMID- 15520307
TI  - Pulmonary hypertension and right heart failure in pituitary adenylate cyclase
      activating polypeptide type I receptor-deficient mice.
AB  - BACKGROUND: Pituitary adenylate cyclase-activating polypeptide (PACAP), acting
      via 3 different G protein-coupled receptors, has been implicated in the
      regulation of several homeostatic systems in the body, including cardiopulmonary
      control. To define the physiologic role of the PACAP-preferring type I receptor,
      PAC1, in cardiopulmonary function, we developed a mutant mouse strain lacking
      functional PAC1 receptors. METHODS AND RESULTS: When PAC1-deficient mice were
      crossed onto a C57BL/6 background, almost all mutants died during the second
      postnatal week. Whereas mutant mice were indistinguishable from their wild-type
      littermates at birth, they showed progressive weakness and died from rapidly
      developing heart failure. Right ventricles of PAC1 mutants were massively dilated
      and showed cardiac myocyte hypertrophy, whereas left ventricular structure was
      unaltered. On direct cardiac catheterization, right ventricular pressure was
      elevated by 45% in PAC1-deficient mice, indicating increased pulmonary artery
      pressure, as no malformations were detected in the valves or outflow tract of the
      right ventricle. Consistent with elevated pulmonary pressure, lung capillary
      density was decreased by 30% and small pulmonary arteries of mutant mice had
      significant vascular smooth muscle cell hypertrophy compared with wild-type mice.
      CONCLUSIONS: Whereas PACAP induces vasodilation in isolated pulmonary vessels in
      wild-type mice, the absence of its specific receptor PAC1 causes pulmonary
      hypertension and right heart failure after birth. These in vivo findings
      demonstrate the crucial importance of PAC1-mediated signaling for the maintenance
      of normal pulmonary vascular tone during early postnatal life.

PMID- 15520308
TI  - Value of noncontact mapping for identifying left ventricular scar in an ovine
      model.
AB  - BACKGROUND: We assessed the hypothesis that "virtual electrograms" from a
      noncontact mapping system (EnSite 3000) could be used to localize myocardial
      scar. METHODS AND RESULTS: Myocardial infarctions were induced in sheep by
      inflating an angioplasty balloon in the left anterior descending coronary artery
      for 3 hours. Scar mapping was performed on 8 sheep without inducible ventricular
      tachycardia by use of the noncontact mapping system and a 256-channel contact
      mapping system. Transmural mapping needles were inserted into myocardial regions
      that were (1) scarred, (2) peripheral to the scar, and (3) distant from the scar.
      Unipolar electrograms were exported from both systems and analyzed on a personal
      computer workstation. The percentage of myocardial scarring at each needle site
      was assessed histologically. Pearson's correlation was used to assess the degree
      of association between various electrogram characteristics and the presence of
      myocardial scarring. The only noncontact electrogram characteristic that showed
      any association with the presence of myocardial scarring was the negative slope
      duration (contact, r=0.62, P<0.001; noncontact, r=0.23, P=0.004). The other
      electrogram characteristics studied were electrogram maximal deflection (contact,
      r=0.38, P<0.001; noncontact, r=0.03, P=0.75) and minimal slope (contact, r=0.42,
      P<0.001; noncontact, r=0.05, P=0.54). CONCLUSIONS: Noncontact electrograms do not
      reliably identify ventricular scar. Alternative strategies such as importing
      computed tomography images into the geometry should be used when scar
      localization is important.

PMID- 15520309
TI  - Evidence for a heritable component in death resulting from aortic and mitral
      valve diseases.
AB  - BACKGROUND: Cardiac valvular diseases contribute to >42,000 deaths yearly in the
      United States, but the role of genetics in these deaths is unknown. This study
      evaluated the familiality of death resulting from aortic, mitral, and all
      valvular diseases using a population-based genealogy linked to death records.
      METHODS AND RESULTS: The Utah Population Database contains >2 million individual
      records with genealogy data and 250,000 linked death certificates. Nonrheumatic
      aortic (n=932), mitral (n=1165), and all valvular (n=2504) disease deaths and
      rheumatic heart disease deaths (n=4713) were studied. Familial relative risks
      (FRRs) were assessed for first- and second-degree relatives. Familiality was also
      evaluated with the genealogical index of familiality, which considers all
      relationships in the Utah Population Database. FRRs were increased only for
      mitral valve death in both first-degree (FRR, 2.55; P<0.0001) and second-degree
      (FRR, 1.67; P<0.0001) relatives. Genealogical index of familiality analysis
      showed significant excess relatedness for all groups (P<0.001). Genealogical
      index of familiality results (P<0.001) for early age at death cases showed higher
      mean relatedness, a common characteristic of heritable disorders. Excess
      familiality extended to distant relatives for mitral (second-degree relatives)
      and aortic (beyond second-degree relatives) valve death. CONCLUSIONS: Deaths
      resulting from nonrheumatic mitral and aortic diseases clustered among both close
      and distant relatives, especially among early age at death cases, suggesting a
      significant genetic component in death resulting from valvular diseases. Future
      studies should focus on gene discovery.

PMID- 15520310
TI  - Prevention of iatrogenic atrial tachycardia after ablation of atrial
      fibrillation: a prospective randomized study comparing circumferential pulmonary
      vein ablation with a modified approach.
AB  - BACKGROUND: Circumferential pulmonary vein ablation (CPVA) is effective in curing
      atrial fibrillation (AF), but new-onset left atrial tachycardia (AT) is a
      potential complication. We evaluated whether a modified CPVA approach including
      additional ablation lines on posterior wall and the mitral isthmus would reduce
      the incidence of AT after PV ablation. METHODS AND RESULTS: A total of 560
      patients (291 men, 52%; age, 56.5+/-7.3 years) entered the study; 280 were
      randomized to CPVA alone (group 1) and 280 to modified CPVA (group 2). The
      primary end point was freedom from AT after the procedure. In group 1, 28
      patients (10%) experienced new-onset AT, and 41 (14.3%) experienced recurrent AF.
      In group 2, 11 patients (3.9%) experienced AT, and 36 (12.9%) had recurrent AF.
      Group 1 was more likely to experience AT than group 2 (P=0.005). Freedom from AF
      after ablation was similar in both groups (P=0.57). Among those in group 1, gap
      related macroreentrant AT was documented in 23 of the 28 patients (82%), and
      focal AT was found in 5 (18%). In group 2, gap-related macroreentrant AT was
      found in 8 of the 11 patients (73%), and focal AT was seen in 3 (27%). Two
      patients in group 1 and 1 patient in group 2 had both AT and AF. The strongest
      predictor of AT was the presence of gaps (P<0.001). CONCLUSIONS: Modified CPVA is
      as effective as CPVA in preventing AF but is associated with a lower risk of
      developing incessant AT.

PMID- 15520311
TI  - Increased myocardial collagen content in transgenic rats overexpressing cardiac
      angiotensin-converting enzyme is related to enhanced breakdown of N-acetyl-Ser
      Asp-Lys-Pro and increased phosphorylation of Smad2/3.
AB  - BACKGROUND: Although increased activity of angiotensin-converting enzyme (ACE)
      has been associated with increased cardiac collagen, no studies to date have
      established a direct cause-and-effect relation between the two. METHODS AND
      RESULTS: We used transgenic rats that overexpress human ACE selectively in the
      myocardium. Two independent heterozygous transgenic rat lines were studied, one
      expressing 2 to 3 copies (L1172) and the other expressing 5 to 10 copies (L1173)
      of the ACE transgene. These rats were normotensive but developed a proportionate
      increase in myocardial collagen depending on the ACE gene dose (up to 2.5-fold,
      P<0.01), but cardiac angiotensin II levels remained normal, whereas collagen
      content reversed to control levels on ACE inhibition. To explain these changes,
      we investigated N-acetyl-Ser-Asp-Lys-Pro (AcSDKP), an alternative substrate that
      is catabolized exclusively by ACE. Increased cardiac expression of ACE was
      paralleled by a reciprocal decrease in cardiac AcSDKP and a proportionate
      increase in phosphorylated Smad2 and Smad3, all of which normalized after both
      ACE inhibition and AcSDKP infusion. Furthermore, a functional link of this
      signaling cascade was demonstrated, because AcSDKP inhibited Smad3
      phosphorylation in a dose-dependent manner in cultured cardiac fibroblasts and in
      vivo. CONCLUSIONS: Our findings suggest that increased cardiac ACE activity can
      increase cardiac collagen content by degradation of AcSDKP, an inhibitor of the
      phosphorylation of transforming growth factor-beta signaling molecules Smad2 and
      Smad3. This implies that the antifibrotic effects of ACE inhibitors are mediated
      in part by increasing cardiac AcSDKP, with subsequent inhibition of Smad 2/3
      phosphorylation.

PMID- 15520312
TI  - Abnormal myocardial presynaptic norepinephrine recycling in patients with Brugada
      syndrome.
AB  - BACKGROUND: Life-threatening ventricular tachyarrhythmias can occur in young
      patients without structural heart disease (idiopathic forms). In many patients,
      these are typically triggered by an increased sympathetic tone, eg, by physical
      or mental stress. In contrast, in Brugada syndrome, ventricular tachyarrhythmias
      more often occur during rest or sleep when the vagal tone is predominant.
      Furthermore, adrenergic agonists can reduce the level of ST-segment elevation,
      whereas it is increased by parasympathetic agonists or adrenergic antagonists.
      The aim of this study was to investigate presynaptic and postsynaptic myocardial
      sympathetic function in patients with Brugada syndrome. METHODS AND RESULTS: Nine
      patients with Brugada syndrome (6 male, 3 female; age, 41+/-13 years) were
      enrolled in this study. The cardiac autonomic nervous system was assessed
      noninvasively, quantifying myocardial presynaptic and postsynaptic sympathetic
      function by means of positron emission tomography with the norepinephrine
      analogue 11C-Hydroxyephedrine (11C-HED) and the nonselective beta-blocker 11C-CGP
      12177 (11C-CGP). Presynaptic sympathetic norepinephrine recycling, assessed by
      11C-HED, was globally increased in patients with Brugada syndrome compared with a
      group of age-matched healthy control subjects (92.9+/-16.2 mL/g versus 69.1+/
      14.2 mL/g; P<0.05), whereas postsynaptic beta-adrenoceptor density, assessed by
      11C-CGP, was similar in patients and control subjects (10.4+/-6.7 pmol/g versus
      10.2+/-2.9 pmol/g; P=NS). CONCLUSIONS: The present study on autonomic innervation
      in Brugada syndrome describes an enhanced presynaptic norepinephrine recycling
      with preserved beta-adrenoceptor density, further supporting the hypothesis of an
      autonomic dysfunction in Brugada syndrome. This is a further step toward the
      understanding of the pathophysiology of the disease with potential future impact
      on therapeutic strategies.

PMID- 15520313
TI  - Technique and results of linear ablation at the mitral isthmus.
AB  - BACKGROUND: This prospective clinical study evaluates the feasibility and
      efficacy of combined linear mitral isthmus ablation and pulmonary vein (PV)
      isolation in patients with paroxysmal atrial fibrillation (AF). METHODS AND
      RESULTS: One hundred consecutive patients (13 women; age 55+/-10 years) with drug
      refractory, symptomatic paroxysmal AF underwent PV isolation and linear ablation
      of the cavotricuspid isthmus and the mitral isthmus (lateral mitral annulus to
      the left inferior PV). They were compared with 100 consecutive patients (14
      women; age, 52+/-10 years) undergoing PV isolation and cavotricuspid ablation
      without mitral isthmus ablation. Bidirectional mitral isthmus block was confirmed
      by demonstrating (1) a parallel corridor of double potentials during coronary
      sinus (CS) pacing, (2) an activation detour by pacing either side of the line,
      and (3) differential pacing techniques. Isolation of all PVs and cavotricuspid
      isthmus ablation were performed successfully in all. Mitral isthmus block was
      achieved in 92 patients after 20+/-10 minutes of endocardial radiofrequency
      application and an additional 5+/-4 minutes of epicardial radiofrequency
      application from within the CS in 68, resulting in a conduction delay of 151+/-26
      ms during CS pacing. Thirty-two patients with mitral isthmus ablation compared
      with 49 without had recurrent atrial arrhythmia (P=0.02) requiring further
      ablation. At 1 year after the last procedure, 87 patients with mitral isthmus
      ablation and 69 without (P=0.002) were arrhythmia free without antiarrhythmic
      drugs, mitral isthmus ablation being the only factor associated with long-term
      success (RR for AF recurrence, 0.2; CI, 0.1 to 0.4; P<0.001). CONCLUSIONS:
      Catheter ablation of the mitral isthmus results consistently in demonstrable
      conduction block and is associated with a high cure rate for paroxysmal AF.

PMID- 15520314
TI  - Transcription enhancer factor-1-related factor-transgenic mice develop cardiac
      conduction defects associated with altered connexin phosphorylation.
AB  - BACKGROUND: Conduction system defects and slowed ventricular conduction are
      common in patients with systolic dysfunction and contribute to arrhythmias and
      sudden death. In animal models of heart failure, cardiac alpha1-adrenergic
      signaling is constitutively activated. Here, we report the effects of
      constitutive activation of alpha1-adrenergic signaling on connexin
      phosphorylation and cardiac conduction. METHODS AND RESULTS: Transgenic mice were
      generated with cardiac-specific overexpression of the transcription factor RTEF-1
      (transcription enhancer factor-1-related factor), which mediates alpha1
      adrenergic signaling in cardiac myocytes. Surface and intracardiac ECGs revealed
      prolongation of the PR, QRS, and AH intervals and the appearance of progressive
      atrial arrhythmias in RTEF-1 mice. Optical mapping using voltage-sensitive dye
      revealed slower conduction velocities across the atrial and ventricular
      myocardium. Intercellular dye transfer between RTEF-1 transgenic cardiac myocytes
      confirmed impaired conduction at the cellular level. Conduction defects were
      correlated with dephosphorylation of connexin40 and connexin43 and upregulation
      of protein phosphatase 1beta (PP1beta). Overexpression of PP1beta in HeLa cells
      dephosphorylated cardiac connexin. Confocal microscopy revealed increased levels
      of dephosphorylated connexin43 at the cardiac gap junctions in RTEF-1 mice,
      suggesting that defective conduction is a result of impaired gap-junction
      conductance rather than assembly. CONCLUSIONS: Constitutive activation of alpha1
      adrenergic signaling through the RTEF-1 transcription factor results in chronic
      elevation of PP1beta expression and connexin dephosphorylation. This mechanism
      may underlie some defects in cardiac conduction.

PMID- 15520315
TI  - Testosterone induces cytoprotection by activating ATP-sensitive K+ channels in
      the cardiac mitochondrial inner membrane.
AB  - BACKGROUND: Whereas in the past, androgens were mainly believed to exert adverse
      effects on the cardiovascular system, recent experimental data postulate a
      benefit of testosterone for recovery of myocardial function after
      ischemia/reperfusion injury. Thus, we examined whether testosterone might improve
      myocardial tolerance to ischemia due to activation of mitochondrial (mitoK(ATP))
      and/or sarcoplasmatic (sarcK(ATP)) K(ATP) channels. METHODS AND RESULTS: In a
      cellular model of ischemia, testosterone significantly decreased the rate of
      ischemia-induced death of cardiomyocytes that could be prevented by 5
      hydroxydecainoic acid but was unaffected by the sarcK(ATP) blocker HMR1098 and
      the testosterone receptor antagonist flutamide. To index mitoK(ATP),
      mitochondrial flavoprotein fluorescence was measured. Testosterone induced a
      highly significant increase in mitochondrial flavoprotein fluorescence in intact
      myocytes and isolated mitoplasts that could be abolished by 5-hydroxydecainoic
      acid. Testosterone-mediated flavoprotein oxidation of mitoplasts was K+ dependent
      and ATP sensitive. In mitoplast-attached single-channel recordings, testosterone
      directly activated an ATP-sensitive K+ channel of the inner mitochondrial
      membrane. Addition of the K(ATP) channel opener diazoxide and pinacidil to the
      cytosolic solution activated the ATP-sensitive K+ current comparable to
      testosterone, whereas 5-hydroxydecainoic acid and glibenclamide inhibited the
      testosterone-induced current. Patch-clamp experiments of intact myocytes in whole
      cell configuration did not demonstrate any effect of testosterone on sarcK(ATP)
      channels. CONCLUSIONS: Our results provide direct evidence for the existence of
      cardiac mitoK(ATP) and a link between testosterone-induced cytoprotection and
      activation of mitoK(ATP). Endogenous testosterone might play a more important
      role in recovery after myocardial infarction than is currently assumed.

PMID- 15520316
TI  - Multiscale motion mapping: a novel computer vision technique for quantitative,
      objective echocardiographic motion measurement independent of Doppler: first
      clinical description and validation.
AB  - BACKGROUND: Objective, quantitative, segmental noninvasive/bedside measurement of
      cardiac motion is highly desirable in cardiovascular medicine, but current
      technology suffers from significant drawbacks, such as subjectivity of
      conventional echocardiographic reading, angle dependence of tissue Doppler
      measurements, radiation exposure by computer tomography, and infrastructure
      requirements in MRI. We hypothesized that computer vision technology could
      represent a powerful new paradigm for quantification in echocardiography. METHODS
      AND RESULTS: We present multiscale motion mapping, a novel computer vision
      technology that is based on mathematical image processing and that exploits
      echocardiographic information in a fashion similar to the human visual system. It
      allows Doppler- and border-independent determination of motion and deformation in
      echocardiograms at arbitrary locations. Correctness of the measurements was
      documented in synthetic echocardiograms and phantom experiments. Exploratory case
      studies demonstrated its usefulness in a series of complex motion analyses that
      included abnormal septal motion and analysis of myocardial twisting. Clinical
      applicability was shown in a consecutive series of echocardiograms, in which good
      feasibility, good correlation with expert rating, and good intraobserver and
      interobserver concordance were documented. Separate assessment of 2D displacement
      and deformation at the same location was successfully applied to elucidate
      paradoxical septal motion, a common clinical problem. CONCLUSIONS: This is the
      first clinical report of multiscale motion mapping, a novel approach to
      echocardiographic motion quantification. For the first time, full 2D
      echocardiographic assessment of both motion and deformation is shown to be
      feasible. Overcoming current limitations, this computer vision-based technique
      opens a new door to objective analysis of complex heart motion.

PMID- 15520317
TI  - Alterations of left ventricular myocardial characteristics associated with
      obesity.
AB  - BACKGROUND: Obesity is associated with heart failure, but an effect of weight,
      independent of comorbidities, on cardiac structure and function is not well
      established. We sought whether body mass index (BMI) and insulin levels were
      associated with subclinical myocardial disturbances. METHODS AND RESULTS:
      Transthoracic echocardiography, myocardial Doppler-derived systolic (sm) and
      early diastolic velocity (em), strain and strain rate imaging and tissue
      characterization with cyclic variation (CVIB), and calibrated integrated
      backscatter (cIB) were obtained in 109 overweight or obese subjects and 33
      referents (BMI <25 kg/m2). BMI correlated with left ventricular (LV) mass and
      wall thickness (P<0.001). Severely obese subjects (BMI >35) had reduced LV
      systolic and diastolic function and increased myocardial reflectivity compared
      with referents, evidenced by lower average long-axis strain, sm, cIB, lower CVIB,
      and reduced em, whereas LV ejection fraction remained normal. Differences in
      regional or global strain, sm, and em were identified between the severely obese
      (BMI >35) and the referent patients (P<0.001). Similar but lesser degrees of
      reduced function by sm, em, and basal septal strain and increased reflectivity by
      cIB were present in overweight (BMI, 25 to 29.9) and mildly obese (BMI, 30 to 35)
      groups (P<0.05). Although tissue Doppler measures were not associated with
      duration of obesity, they did correlate with fasting insulin levels and reduced
      exercise capacity. BMI was independently related to average LV strain (beta=0.40,
      P=0.02), sm (beta=-0.36, P=0.002), and em (beta=-0.41, P<0.001). CONCLUSIONS:
      Overweight subjects without overt heart disease have subclinical changes of LV
      structure and function even after adjustment for mean arterial pressure, age,
      gender, and LV mass.

PMID- 15520318
TI  - Galectin-3 marks activated macrophages in failure-prone hypertrophied hearts and
      contributes to cardiac dysfunction.
AB  - BACKGROUND: Inflammatory mechanisms have been proposed to be important in heart
      failure (HF), and cytokines have been implicated to add to the progression of HF.
      However, it is unclear whether such mechanisms are already activated when
      hypertrophied hearts still appear well-compensated and whether such early
      mechanisms contribute to the development of HF. METHODS AND RESULTS: In a
      comprehensive microarray study, galectin-3 emerged as the most robustly
      overexpressed gene in failing versus functionally compensated hearts from
      homozygous transgenic TGRmRen2-27 (Ren-2) rats. Myocardial biopsies obtained at
      an early stage of hypertrophy before apparent HF showed that expression of
      galectin-3 was increased specifically in the rats that later rapidly developed
      HF. Galectin-3 colocalized with activated myocardial macrophages. We found
      galectin-3-binding sites in rat cardiac fibroblasts and the extracellular matrix.
      Recombinant galectin-3 induced cardiac fibroblast proliferation, collagen
      production, and cyclin D1 expression. A 4-week continuous infusion of low-dose
      galectin-3 into the pericardial sac of healthy Sprague-Dawley rats led to left
      ventricular dysfunction, with a 3-fold differential increase of collagen I over
      collagen III. Myocardial galectin-3 expression was increased in aortic stenosis
      patients with depressed ejection fraction. CONCLUSIONS: This study shows that an
      early increase in galectin-3 expression identifies failure-prone hypertrophied
      hearts. Galectin-3, a macrophage-derived mediator, induces cardiac fibroblast
      proliferation, collagen deposition, and ventricular dysfunction. This implies
      that HF therapy aimed at inflammatory responses may need to be targeted at the
      early stages of HF and probably needs to antagonize multiple inflammatory
      mediators, including galectin-3.

PMID- 15520319
TI  - Muscle mechanoreflex and metaboreflex responses after myocardial infarction in
      rats.
AB  - BACKGROUND: During exercise, the sympathetic nervous system is activated and
      blood pressure and heart rate increase. In heart failure (HF), the muscle
      metaboreceptor contribution to sympathetic outflow is attenuated and the
      mechanoreceptor contribution is accentuated. Previous studies suggest that (1)
      capsaicin stimulates muscle metabosensitive vanilloid receptor subtype 1 (VR1),
      inducing a neurally mediated pressor response, and (2) activation of ATP
      sensitive P2X receptors enhances the pressor response seen when muscle
      mechanoreceptors are engaged by muscle stretch. Thus, we hypothesized that the
      pressor response to VR1 stimulation would be smaller and the sensitizing effects
      of P2X stimulation greater in rats with HF due to chronic myocardial infarction
      (MI) than in controls. METHODS AND RESULTS: Eight to 14 weeks after coronary
      ligation, rats with infarcts >35% had an increased left ventricular end-diastolic
      pressure and a marked increase in heart weight. Capsaicin injected into the
      arterial supply of the hindlimb increased blood pressure by 39% (baseline, 93.9+/
      9.5 mm Hg) in control animals but only by 8% (baseline, 94.8+/-10.1 mm Hg) in
      rats with large MIs (P<0.05). P2X receptor stimulation by alpha,beta-methylene
      ATP enhanced the pressor response to muscle stretch by 42% in control animals and
      by 72% in rats with large MIs (P<0.05). CONCLUSIONS: Compared with control
      animals, cardiovascular responses to VR1 stimulation are blunted and P2X-mediated
      responses are augmented in rats with HF owing to large MIs.

PMID- 15520320
TI  - Early intertwin differences in myocardial performance during the twin-to-twin
      transfusion syndrome.
AB  - BACKGROUND: In the twin-to-twin transfusion syndrome (TTTS), pressure rather than
      volume overload is increasingly considered as a key factor in the pathogenesis of
      the cardiomyopathy of the recipient twin. If this is the case, cardiac
      dysfunction should be among the first signs observed with TTTS. The objective of
      this study was to determine whether intertwin differences in myocardial function
      are modified early in the course of TTTS and whether they can help to
      differentiate this condition from intrauterine growth restriction (IUGR). METHODS
      AND RESULTS: Eight variables were analyzed on the first fetal echocardiography on
      21 pairs of twins with TTTS and 11 with IUGR. No difference was found between the
      2 groups for the cardiothoracic ratio, pulsatility indices in the umbilical and
      middle cerebral arteries, and peak velocity of the middle cerebral artery.
      Significant difference was found for ventricular septal thickness, but with no
      association with the conditions under study. With TTTS, left ventricular
      shortening fraction was consistently greater in the donor twins, and myocardial
      performance indices (MPIs) were elevated in the recipient twins. This increase in
      MPI was caused by a lengthening of the isovolumic periods compared with those of
      the donor twin: left ventricular and right ventricular isovolumic periods 0.105+/
      0.047 and 0.097+/-0.026 seconds, respectively, for the recipient twins versus
      0.0561+/-0.46 and 0.065+/-0.03 seconds, respectively, for the donor twins
      (P<0.001). These changes in the isovolumic periods were mainly due to significant
      prolongation of isovolumic relaxation times. A change in left ventricular MPI >
      or =0.09 combined with a change in right ventricular MPI > or =0.05 would
      identify a TTTS with a sensitivity of 75% and a false-positive rate of 9%.
      CONCLUSIONS: The observed diastolic function impairment goes along with the
      pressure-overload pathogenic concept proposed in TTTS. Assessment of intertwin
      difference in MPI is a valuable tool for early differential diagnosis between
      TTTS and isolated IUGR.

PMID- 15520321
TI  - Coenzyme Q10 combined with mild hypothermia after cardiac arrest: a preliminary
      study.
AB  - BACKGROUND: Therapeutic hypothermia can improve survival after cardiopulmonary
      resuscitation (CPR). Coenzyme Q10 (CoQ10) has shown a protective effect in
      neurodegenerative disorders. We investigated whether combining mild hypothermia
      with CoQ10 after out-of-hospital cardiac arrest provides additional benefit.
      METHODS AND RESULTS: Forty-nine patients were randomly assigned to either
      hypothermia plus CoQ10 or hypothermia plus placebo after CPR. Hypothermia with a
      core temperature of 35 degrees C was instituted for 24 hours. Liquid CoQ10 250 mg
      followed by 150 mg TID for 5 days or placebo was administered through nasogastric
      tube. Age, sex, premorbidity, cause of arrest, conditions of CPR, and degree of
      hypoxia were similar in both groups; no side effects of CoQ10 were identified.
      Three-month survival in the CoQ10 group was 68% (17 of 25) and 29% (7 of 24) in
      the placebo group (P=0.0413). Nine CoQ10 patients versus 5 placebo patients
      survived with a Glasgow Outcome Scale of 4 or 5. Mean serum S100 protein 24 hours
      after CPR was significantly lower in the CoQ10 group (0.47 versus 3.5 ng/mL).
      CONCLUSIONS: Combining CoQ10 with mild hypothermia immediately after CPR appears
      to improve survival and may improve neurological outcome in survivors.

PMID- 15520323
TI  - Simvastatin prevents vascular hyporeactivity during inflammation.
AB  - BACKGROUND: There is growing evidence that statins exert anti-inflammatory and
      antioxidative vascular actions that are independent of lipid lowering. We tested
      whether hyporeactivity to the endothelium-dependent vasodilator acetylcholine
      (ACh) and the vasoconstrictor norepinephrine (NE) during acute experimental
      inflammation could be prevented by simvastatin. METHODS AND RESULTS: In a
      randomized, placebo-controlled, parallel group study, forearm blood flow (FBF)
      responses to NE, ACh, and the endothelium-independent vasodilator nitroglycerin
      (NTG) were assessed at baseline, after 4 days of simvastatin 80 mg PO or placebo
      treatment, and during Escherichia coli endotoxin (lipopolysaccharide [LPS])
      induced inflammation in 20 healthy volunteers. Additionally, markers of
      inflammation and neutrophil oxidative burst were assessed. Simvastatin and
      placebo had no effect on FBF or oxidative/inflammatory markers. LPS
      administration decreased the responses of FBF to NE by 43% (P<0.05) and decreased
      responses to ACh by 48% (P<0.05) but did not decrease FBF responses to NTG.
      Simvastatin completely preserved responses to NE and to ACh. The LPS-induced
      increases in neutrophil oxidative burst and plasma tumor necrosis factor-alpha
      concentrations were mitigated by simvastatin (P<0.05 versus placebo).
      CONCLUSIONS: This study demonstrates potent vasoprotective properties of high
      dose simvastatin during endotoxemia that may be useful for patients with acute
      systemic inflammation and associated vascular hyporeactivity.

PMID- 15520322
TI  - Value of electrocardiographic parameters and ajmaline test in the diagnosis of
      Brugada syndrome caused by SCN5A mutations.
AB  - BACKGROUND: The Brugada syndrome is an arrhythmogenic disease caused in part by
      mutations in the cardiac sodium channel gene, SCN5A. The electrocardiographic
      pattern characteristic of the syndrome is dynamic and is often absent in affected
      individuals. Sodium channel blockers are effective in unmasking carriers of the
      disease. However, the value of the test remains controversial. METHODS AND
      RESULTS: We studied 147 individuals representing 4 large families with SCN5A
      mutations. Of these, 104 were determined to be at possible risk for Brugada
      syndrome and underwent both electrocardiographic and genetic evaluation. Twenty
      four individuals displayed an ECG diagnostic of Brugada syndrome at baseline. Of
      the remaining, 71 received intravenous ajmaline. Of the 35 genetic carriers who
      received ajmaline, 28 had a positive test and 7 a negative ajmaline test. The
      sensitivity, specificity, and positive and negative predictive values of the drug
      challenge were 80% (28:35), 94.4% (34:36), 93.3% (28:30), and 82.9% (34:41),
      respectively. Penetrance of the disease phenotype increased from 32.7% to 78.6%
      with the use of sodium channel blockers. In the absence of ST-segment elevation
      under baseline conditions, a prolonged P-R interval, but not incomplete right
      bundle-branch block or early repolarization patterns, indicates a high
      probability of an SCN5A mutation carrier. CONCLUSIONS: In families with Brugada
      syndrome, the data suggest that ajmaline testing is valuable in the diagnosis of
      SCN5A carriers. In the absence of ST-segment elevation at baseline, family
      members with first-degree atrioventricular block should be suspected of carrying
      the mutation. An ajmaline test is often the key to making the proper diagnosis in
      these patients.

PMID- 15520324
TI  - Inhibition of vascular smooth muscle cell proliferation and neointimal formation
      in injured arteries by a novel, oral mitogen-activated protein
      kinase/extracellular signal-regulated kinase inhibitor.
AB  - BACKGROUND: Mitogen-activated protein kinases (MAPKs) are rapidly induced after
      arterial injury in different animal models. However, their precise role in
      vascular smooth muscle cell (VSMC) proliferation and neointimal formation in vivo
      remains to be determined. METHODS AND RESULTS: We investigated the properties of
      a novel, selective inhibitor of the upstream kinase, MAPK/extracellular signal
      regulated kinase, that is orally active (PD0185625). In vitro, PD0185625 was
      shown to abrogate p44/p42 MAPK activation in VSMCs after serum stimulation. This
      was associated with a dose-dependent inhibition of VSMC proliferation. In vivo,
      PD0185625 was administered orally to rats (200 mg x kg(-1) x d(-1)) beginning 2
      days before balloon injury of the left carotid artery and for 2 weeks thereafter.
      Treatment with PD0185625 led to nearly complete inhibition of p44/p42 MAPK
      activation after balloon injury. This resulted in a significant decrease in VSMC
      proliferation (BrdU incorporation) at day 7 after injury. Moreover, neointimal
      formation was significantly reduced in PD0185625-treated animals at 14 and 28
      days after arterial injury. We found that PD0185625 did not increase the rate of
      apoptotic cell death but prevented cell cycle progression and induced a G1 block.
      CONCLUSIONS: PD0185625 reduced neointimal formation after arterial injury. The
      mechanism involved inhibition of VSMC proliferation via a G1 block of the cell
      cycle. Orally active selective MAPK inhibitors could represent a novel
      therapeutic approach for vascular diseases.

PMID- 15520325
TI  - Statins enhance migratory capacity by upregulation of the telomere repeat-binding
      factor TRF2 in endothelial progenitor cells.
AB  - BACKGROUND: Cultivation of endothelial progenitor cells (EPCs) leads to premature
      replicative senescence, limiting ex vivo expansion for potential clinical cell
      therapy. Recent studies have linked senescence to the dysfunction of telomeres,
      the "ends" of chromosomes, via the so-called mitotic clock or culture-induced
      stress. The purpose of this study was to elucidate a possible role of telomere
      biology in the functional augmentation of EPCs by statins. METHODS AND RESULTS:
      Human EPCs were isolated from peripheral blood. Using flow cytometry after
      fluorescence in situ hybridization with a telomere-specific (C3TA2)3 peptide
      nucleic acid probe (Flow-FISH), we found mean telomere length in untreated EPCs
      from healthy subjects to range between 8.5+/-0.2 and 11.1+/-0.5 kb with no change
      over 6 days of culture, excluding telomere erosion as one cause for premature
      senescence. Although mean telomere length did not differ between statin-treated
      and untreated EPCs, atorvastatin (0.1 micromol/L) and mevastatin (1.0 micromol/L)
      both led to a more than 3-fold increase in the expression of the telomere capping
      protein TRF2 (telomere repeat-binding factor), as shown by immunoblotting,
      whereas quantitative reverse transcription-polymerase chain reaction demonstrated
      no increase in TRF2 mRNA. Telomere dysfunction of EPCs was also paralleled by a 4
      fold increase in the DNA damage checkpoint-kinase 2 (Chk2). Conversely, statin
      cotreatment or overexpression of TRF2 completely suppressed Chk2 induction.
      Finally, overexpression of a dominant negative mutant of the TRF2 protein
      abrogated statin-induced enhancement of migratory activity down to baseline
      values. CONCLUSIONS: Ex vivo culturing of EPCs leads to "uncapping" of telomeres,
      indicated by the loss of TRF2. Statin cotreatment of EPCs prevents impairment of
      their functional capacity by a TRF2-dependent, posttranscriptional mechanism.
      This is the first time a beneficial effect of statins on telomere biology has
      been described.

PMID- 15520326
TI  - Long-term amiodarone administration remodels expression of ion channel
      transcripts in the mouse heart.
AB  - BACKGROUND: The basis for the unique effectiveness of long-term amiodarone
      treatment on cardiac arrhythmias is incompletely understood. The present study
      investigated the pharmacogenomic profile of amiodarone on genes encoding ion
      channel subunits. METHODS AND RESULTS: Adult male mice were treated for 6 weeks
      with vehicle or oral amiodarone at 30, 90, or 180 mg x kg(-1) x d(-1). Plasma and
      myocardial levels of amiodarone and N-desethylamiodarone increased dose
      dependently, reaching therapeutic ranges observed in human. Plasma
      triiodothyronine levels decreased, whereas reverse triiodothyronine levels
      increased in amiodarone-treated animals. In ECG recordings, amiodarone dose
      dependently prolonged the RR, PR, QRS, and corrected QT intervals. Specific
      microarrays containing probes for the complete ion-channel repertoire (IonChips)
      and real-time reverse transcription-polymerase chain reaction experiments
      demonstrated that amiodarone induced a dose-dependent remodeling in multiple ion
      channel subunits. Genes encoding Na+ (SCN4A, SCN5A, SCN1B), connexin (GJA1), Ca2+
      (CaCNA1C), and K+ channels (KCNA5, KCNB1, KCND2) were downregulated. In patch
      clamp experiments, lower expression of K+ and Na+ channel genes was associated
      with decreased I(to,f), I(K,slow), and I(Na) currents. Inversely, other K+
      channel alpha- and beta-subunits, such as KCNA4, KCNK1, KCNAB1, and KCNE3, were
      upregulated. CONCLUSIONS: Long-term amiodarone treatment induces a dose-dependent
      remodeling of ion-channel expression that is correlated with the cardiac
      electrophysiologic effects of the drug. This profile cannot be attributed solely
      to the amiodarone-induced cardiac hypothyroidism syndrome. Thus, in addition to
      the direct effect of the drug on membrane proteins, part of the therapeutic
      action of long-term amiodarone treatment is likely related to its effect on ion
      channel transcripts.

PMID- 15520327
TI  - Heparin-induced thrombocytopenia: diagnosis and management.

PMID- 15520328
TI  - Images in cardiovascular medicine. Drug-induced long-QT syndrome with macroscopic
      T-wave alternans.

PMID- 15520329
TI  - Images in cardiovascular medicine. Untreated tetralogy of Fallot with pulmonary
      atresia in a 55-year-old woman: findings from magnetic resonance imaging.

PMID- 15520330
TI  - Prevention Conference VII: Obesity, a worldwide epidemic related to heart disease
      and stroke: Group I: worldwide demographics of obesity.

PMID- 15520331
TI  - Prevention Conference VII: Obesity, a worldwide epidemic related to heart disease
      and stroke: Group II: age-dependent risk factors for obesity and comorbidities.

PMID- 15520332
TI  - Prevention Conference VII: Obesity, a worldwide epidemic related to heart disease
      and stroke: Group III: worldwide comorbidities of obesity.

PMID- 15520333
TI  - Prevention Conference VII: Obesity, a worldwide epidemic related to heart disease
      and stroke: Group IV: prevention/treatment.

PMID- 15520334
TI  - The continuum of risk: vascular pathophysiology, function, and structure.

PMID- 15520335
TI  - Heart rate recovery: predictor of risk today and target of therapy tomorrow?

PMID- 15520336
TI  - Prevention Conference VII: Obesity, a worldwide epidemic related to heart disease
      and stroke: executive summary.

PMID- 15520338
TI  - Pre-med.

PMID- 15520339
TI  - Safety of the trivalent inactivated influenza vaccine among children: a
      population-based study.
AB  - BACKGROUND: To our knowledge, there are no published population-based studies on
      the safety of the inactivated trivalent influenza vaccine among children.
      OBJECTIVE: To screen a large population of children for evidence of increased
      medical visits in the 2 weeks after influenza vaccination compared with 2 control
      periods. Secondary analyses included shorter risk periods and restricted age
      categories. DESIGN: Self-control screening analysis. Children vaccinated from
      January 1, 1993, through December 31, 1999, were randomly divided into 2 equal
      groups. In group 1, risks of outpatient, emergency department, and inpatient
      visits during the 14 days after vaccination were compared with the risks of
      visits in 2 control periods. Significant plausible medically attended events
      identified in group 1 were then analyzed in group 2, using the same 2 control
      periods. Medically attended events significant in both groups were considered
      potentially associated with vaccination and were assessed by medical record
      review. SETTING: Five managed care organizations in the United States.
      PARTICIPANTS: Children younger than 18 years who received an influenza
      vaccination in one of the managed care settings (N = 251 600). MAIN OUTCOME
      MEASURE: Among vaccinated children seen for a medically attended event, the odds
      of the visit occurring in the 2 weeks after vaccination vs during 1 of the 2
      control periods. RESULTS: Study participants incurred 1165, 230, and 489
      different diagnoses during the 14 days after vaccination according to the
      outpatient, emergency department, and inpatient data, respectively. Four
      diagnoses were positively associated with the vaccine in both groups 1 and 2:
      impetigo, dermatitis, uncomplicated diabetes mellitus, and ureteral disorder not
      otherwise specified. After medical record review, impetigo (9 cases) in children
      6 to 23 months old remained significantly associated with vaccination.
      CONCLUSION: This large screening safety study did not reveal any evidence of
      important medically attended events associated with pediatric influenza
      vaccination.

PMID- 15520340
TI  - Childhood severe acute respiratory syndrome in Taiwan and how to differentiate it
      from childhood influenza infection.
AB  - OBJECTIVE: To investigate clinical features and outcomes of children in Taiwan
      with laboratory-confirmed severe acute respiratory syndrome (SARS) vs those of
      children with influenza to differentiate the 2 diseases. DESIGN, SETTING, AND
      PARTICIPANTS: Patients 20 years or younger with clinical, epidemiological, and
      laboratory evidence of SARS from March to July 2003 vs children with virus
      culture-confirmed influenza in a 1:1 age- and sex-matched control group. MAIN
      OUTCOME MEASURES: Rates of symptoms, abnormal laboratory data, and outcomes of
      recovery, sequelae, or death. RESULTS: The 15 SARS patients (9 girls and 6 boys)
      had a median age of 17 years (age range, 4-20 years). Nine patients (60%) were
      infected through household contact, 4 (27%) nosocomially, 1 (7%) through contact
      with a neighbor, and 1 (7%) after returning from Hong Kong. All 15 patients had
      fever, 3 (20%) had chills, and 11 (73%) had cough. Only 1 patient (7%) had sputum
      production; 1 (7%) had rhinorrhea. At presentation, 5 patients (33%) had
      leukopenia, 6 (40%) had lymphopenia, and 5 (33%) had monocytopenia. All children
      recovered without sequelae. Children with SARS had significantly lower incidences
      of rhinorrhea (odds ratio [OR], 0.01; 95% confidence interval [CI], 0.00-0.09),
      sputum production (OR, 0.10; 95% CI, 0.02-0.63), and sore throat (OR, 0.17; 95%
      CI, 0.03-0.85) than children with influenza. Both groups had similar incidences
      of leukopenia or lymphopenia, but SARS patients had a significantly higher
      incidence of monocytopenia (33% vs 0%, P = .04). CONCLUSIONS: Childhood SARS is
      usually not fatal. The absence of rhinorrhea and presence of monocytopenia in
      SARS may distinguish it from influenza.

PMID- 15520341
TI  - Preventing substance use and disordered eating: initial outcomes of the ATHENA
      (athletes targeting healthy exercise and nutrition alternatives) program.
AB  - OBJECTIVES: To implement and to assess the efficacy of a school-based, sport team
      centered program to prevent young female high school athletes' disordered eating
      and body-shaping drug use. DESIGN AND SETTING: Prospective controlled trial in 18
      high schools, with balanced random assignment by school to the intervention and
      usual-care control conditions. PARTICIPANTS: We enrolled 928 students from 40
      participating sport teams. Mean age was 15.4 years, 92.2% were white, and follow
      up retention was 72%. INTERVENTION: The ATHENA (Athletes Targeting Healthy
      Exercise and Nutrition Alternative) curriculum's 8 weekly 45-minute sessions were
      incorporated into a team's usual practice activities. Content was gender
      specific, peer-led, and explicitly scripted. Topics included healthy sport
      nutrition, effective exercise training, drug use and other unhealthy behaviors'
      effects on sport performance, media images of females, and depression prevention.
      MAIN OUTCOME MEASURES: We assessed participants by confidential questionnaire
      prior to and following their sport season. We determined program effects using an
      analysis of covariance-based approach within the Generalized Estimating Equation
      framework. RESULTS: Experimental athletes reported significantly less ongoing and
      new use of diet pills and less new use of athletic-enhancing substances
      (amphetamines, anabolic steroids, and sport supplements) (P<.05 for each). Other
      health-harming actions also were reduced (less riding with an alcohol-consuming
      driver [P = .05], more seat belt use [P<.05], and less new sexual activity
      [P<.05]). The ATHENA athletes had coincident positive changes in strength
      training self-efficacy (P<.005) and healthy eating behaviors (P<.001). Reductions
      occurred in intentions toward future use of diet pills (P<.05), vomiting to lose
      weight (P<.05), and use of tobacco (P<.05) and muscle-building supplements
      (P<.005). The program's curriculum components were altered appropriately
      (controlling mood [P<.005], refusal skills [P = .05], belief in the media
      [P<.005], and perceptions of closest friends' body-shaping drug use [P<.001]).
      CONCLUSIONS: Sport teams are effective natural vehicles for gender-specific, peer
      led curricula to promote healthy lifestyles and to deter disordered eating,
      athletic-enhancing substance use, and other health-harming behaviors.

PMID- 15520342
TI  - Cigarette consumption during childhood and persistence of smoking through
      adolescence.
AB  - BACKGROUND: The childhood cause of adolescent smoking requires prospective study.
      OBJECTIVES: To compare prospective with retrospective estimates of childhood
      smoking and to test cigarette consumption and susceptibility to smoking during
      childhood as predictors of smoking behavior at late adolescence. DESIGN: Eight
      year prospective study. SETTING: From February through April of 1994, 1995, and
      1996, surveys were completed in elementary schools in central North Carolina;
      from February through May 2002, telephone interviews were completed wherever
      participants resided. PARTICIPANTS: Of 868 age-eligible children, 737 (84.9%)
      provided survey data between the ages of 8 and 10 years; of these subjects, 594
      (80.6%) were interviewed at the age of 17 years. MAIN OUTCOME MEASURES: Current,
      established, and daily smoking. RESULTS: Current smoking was reported by 23.0% of
      those having never puffed on a cigarette (abstinent) in childhood vs 42.7% (odds
      ratio [OR], 2.45; 95% confidence interval [CI], 1.58-3.82), 50.0% (OR, 3.36; 95%
      CI, 1.41-8.01), 58.3% (OR, 4.41; 95% CI, 1.46-14.18), and 56.5% (OR, 4.37; 95%
      CI, 1.86-10.29) of those who smoked 1 or fewer, 2 to 4, 5 to 20, and more than 20
      cigarettes, respectively, during childhood. Established smoking was reported by
      15.0% of those abstinent in childhood vs 21.3% (OR, 1.52; 95% CI, 0.89-2.58),
      40.6% (OR, 3.93; 95% CI, 1.61-9.59), 50.0% (OR, 4.96; 95% CI, 1.77-16.18), and
      47.8% (OR, 5.21; 95% CI, 2.20-12.32) of those who smoked 1 or fewer, 2 to 4, 5 to
      20, and more than 20 cigarettes, respectively, during childhood. Daily smoking
      was reported by 10.1% of those abstinent in childhood vs 11.2% (OR, 1.10; 95% CI,
      0.56-2.18), 28.1% (OR, 3.45; 95% CI, 1.24-9.03), 33.3% (OR, 4.47; 95% CI, 1.29
      15.84), and 39.1% (OR, 5.75; 95% CI, 2.35-14.08) of those who smoked 1 or fewer,
      2 to 4, 5 to 20, and more than 20 cigarettes, respectively, during childhood.
      Among abstinent children, high vs low susceptibility to smoking predicted greater
      likelihood of current (37.5% vs 16.7%; OR, 2.98; 95% CI, 1.55-5.74), established
      (32.1% vs 9.3%; OR, 4.81; 95% CI, 2.29-10.07), and daily (21.4% vs 7.0%; OR,
      4.02; 95% CI, 1.71-9.44) smoking at follow-up. CONCLUSION: Relatively small
      increases in the number of cigarettes consumed during childhood are associated
      with significantly higher odds of current, established, and daily smoking in
      adolescence.

PMID- 15520343
TI  - Injuries to the head among children enrolled in special education.
AB  - BACKGROUND: Injuries to the head comprise 20% to 39% of all school-related
      injuries. Head injuries among special education students have not been adequately
      described. OBJECTIVES: (1) To examine the incidence and characteristics of head
      injuries in children enrolled in special education and (2) to determine the
      factors that increase the risk of sustaining a head injury compared with an
      injury to another part of the body. METHODS: Pupil Accident Reports for 6769
      students enrolled in 17 of 18 special education schools in 1 large urban school
      district during the academic years 1994-1998 were reviewed, and information on
      the nature of injury, external cause, and activity was abstracted. Head-injured
      and nonhead-injured cases were identified and compared by race, sex, age,
      characteristics of injury, and disability category. RESULTS: Six hundred ninety
      seven injury events were reported during the 4-year study period. The overall
      injury rate was 4.7 injuries per 100 student-years. Two hundred five children
      (29.4%) sustained injuries to the head, and the rate of head injury was 1.3
      injuries per 100 student-years. Falls were the leading cause of injury. Head
      injuries were most commonly associated with physical education and unstructured
      play and usually occurred on the playground. Disproportionately more head than
      nonhead injuries were sustained in the classroom (12% vs 8%) and the bathroom (9%
      vs 3%). Compared with children with emotional/mental disabilities, children with
      multiple disabilities had the highest risk of a head injury (incidence density
      ratio, 2.4 [95% confidence interval, 1.6-3.5]), followed by children with
      physical disabilities (incidence density ratio, 1.8 [95% confidence interval, 1.1
      3.1]). There appeared to be no significant difference in the rate of head injury
      by sex and age. CONCLUSIONS: Modifications of the classroom, bathroom, and
      playground environments might reduce the risk of head injuries in children
      enrolled in special education. Special modifications and increased supervision
      may, in particular, reduce the risk of head injury for children with physical and
      multiple disabilities.

PMID- 15520344
TI  - Caliber of quality-of-life assessments in congenital heart disease: a plea for
      more conceptual and methodological rigor.
AB  - BACKGROUND: Interest in quality-of-life issues in children, adolescents, and
      adults with congenital heart disease has increased significantly during the past
      decades. In general, quality-of-life research is stimulated by an overall
      interest in outcomes. More specifically, quality-of-life studies add to mortality
      and morbidity data by taking reported physical, psychological, and social
      problems into consideration. However, quality of life can be an ambiguous concept
      that is hindered by methodological weaknesses, a situation that can prevent the
      drawing of firm conclusions. OBJECTIVE: To appraise the conceptual and
      methodological rigor of published quality-of-life assessments in patients with
      congenital heart disease. DESIGN: A review of 70 articles published in the
      medical literature, using the 10 criteria previously developed by Gill and
      Feinstein. For each criterion, the number of articles complying with that
      criterion was counted, and the percentage was calculated. To indicate how well
      individual articles performed on the respective criteria, a summary score was
      calculated by summing the number of criteria an article fulfilled and dividing
      this sum by the number of criteria for which the article was eligible to be
      evaluated; the resulting value was then multiplied by 100. MAIN OUTCOME MEASURE:
      Summary scores ranging from 0, for articles complying with none of the criteria,
      to 100, for articles complying with all of the criteria. RESULTS: We found that
      quality-of-life assessments in patients with congenital heart disease showed
      major conceptual and methodological drawbacks (median summary score, 0).
      Moreover, we found that the term quality of life was often used inappropriately,
      an observation supported by several articles in which the authors drew
      conclusions about patients' quality of life, even though quality of life was not
      specifically measured. CONCLUSIONS: A poor conceptual and methodological basis
      for quality of life implies that many results from quality-of-life studies
      performed in patients with congenital heart disease contribute little to the
      scientific knowledge base of quality of life in this patient population. Future
      quality-of-life studies need to invest in a rigorous conceptualization, an
      adequate operational definition, and a sound measurement of quality of life.

PMID- 15520345
TI  - Asthma and lung function 20 years after wheezing in infancy: results from a
      prospective follow-up study.
AB  - OBJECTIVE: To determine the outcome until adulthood after wheezing in infancy,
      compared with pneumonia in infancy and with controls. DESIGN: An 18- to-20-year
      prospective cohort study. SETTING: Pediatric department at a university hospital,
      providing primary hospital care for a defined population. Patients Fifty-four
      children hospitalized for bronchiolitis and 34 for pneumonia at younger than 2
      years, and 45 controls with no early-life wheezing or hospitalization, were
      studied at median age 19 years. MAIN OUTCOME MEASURES: A questionnaire on asthma
      symptoms and medication, physical examination, flow volume spirometry (FVS),
      methacholine inhalation challenge (MIC), home peak expiratory flow (PEF)
      monitoring, and skin prick testing (SPT) to common inhalant allergens. The 2
      asthma definitions were physician-diagnosed asthma and previously diagnosed
      asthma with recent asthmatic symptoms (physician-diagnosed asthma included).
      RESULTS: By the 2 definitions, asthma was present in 30% (odds ratio [OR], 3.37;
      95% confidence interval [CI], 1.12-10.10) and in 41% (OR 1.38; 95% CI, 0.37-5.21)
      in the bronchiolitis group, in 15% (OR, 5.50; 95% CI, 1.87-16.14) and in 24% (OR,
      2.07; 95% CI, 0.59-7.22) in the pneumonia group, and in 11% in the control group.
      After bronchiolitis, the FVS values were forced vital capacity (FVC), 108% (SD,
      13%) of predicted; forced expiratory volume in 1 second, 98% (SD, 12%); forced
      expiratory volume in 1 second divided by FVC, 91% (SD, 7.6%); midexpiratory flow
      at 50% of the FVC, 74% (SD, 19%); and midexpiratory flow at 25% of the FVC, 74%
      (SD, 22%). Bronchial reactivity by MIC was present in 25 (48%) of 52 subjects in
      the bronchiolitis group, in 13 (42%) of 31 in the pneumonia group, and in 14
      (32%) of 44 in the control group. The prevalence of atopy (positive SPTs) was 48%
      to 63% in the 3 groups. In a logistic regression adjusted for atopy and smoking,
      infantile bronchiolitis was an independent risk factor for asthma by both
      definitions. CONCLUSION: The increased risk for asthma persists until adulthood
      after bronchiolitis in infancy.

PMID- 15520346
TI  - Efficacy of a pediatric emergency department-based influenza vaccination program.
AB  - BACKGROUND: Influenza vaccination effectively reduces influenza-related morbidity
      in children but is underused. The pediatric emergency department is a potential
      intervention point for increasing influenza vaccination in children. OBJECTIVE:
      To assess the effectiveness of a pediatric emergency department-based influenza
      vaccination program. DESIGN: A prospective, randomized, controlled clinical
      trial. PARTICIPANTS: We recruited subjects from persons seeking pediatric
      emergency care at a large tertiary care hospital during influenza vaccination
      season in 2002. Eligible subjects were themselves or had a household member at
      increased risk for influenza complications, according to Advisory Committee on
      Immunization Practices guidelines. INTERVENTIONS: We randomly assigned subjects
      by family to the "vaccine offered" group or the "education only" group. We
      educated both groups about influenza illness, the risks and benefits of influenza
      vaccination, and how to receive influenza vaccination outside the study. We
      offered influenza vaccination to the "vaccine offered" group and later obtained
      telephone reports of the postinfluenza-season vaccination status of both groups.
      RESULTS: Four hundred thirty-seven subjects completed the study (238 from the
      "vaccine offered" group, 199 from the "education only" group). At follow-up, the
      percentage of influenza-vaccinated subjects in the "vaccine offered" group was
      greater than in the "education only" group. This was true for pediatric patients
      (57% vs 36%) (relative risk, 1.59; 95% confidence interval, 1.16-2.16) as well as
      for their accompanying adult and child family members (75% vs 34%) (relative
      risk, 2.19; 95% confidence interval, 1.64-2.92). CONCLUSION: A pediatric
      emergency department-based influenza vaccination program increases vaccination of
      targeted children and family members who use the emergency department during
      influenza vaccination season.

PMID- 15520347
TI  - ATHENA (athletes targeting healthy exercise and nutrition alternatives): a
      promising program up against stiff competition.

PMID- 15520348
TI  - Writing informative abstracts for journal articles.

PMID- 15520349
TI  - Reactions of 2 young children with milk allergy after cutaneous exposure to milk
      containing cosmetic products.

PMID- 15520350
TI  - The message in the silence.

PMID- 15520351
TI  - Philanthropy and medicaid.

PMID- 15520352
TI  - The crucial role of the vanishing school nurse.

PMID- 15520353
TI  - Caffeine consciousness.

PMID- 15520354
TI  - Increasing infant safety in air travel: deficiencies are not limited to child
      restraint systems.

PMID- 15520355
TI  - All things betray thee who betrayest me.

PMID- 15520356
TI  - Brain anatomy in adults with velocardiofacial syndrome with and without
      schizophrenia: preliminary results of a structural magnetic resonance imaging
      study.
AB  - CONTEXT: Velocardiofacial syndrome is associated with interstitial deletions of
      chromosome 22q11, mild to borderline learning disability, characteristic
      dysmorphology, and a high prevalence of schizophrenia. The biological basis for
      this increased risk for schizophrenia is unknown, but people with
      velocardiofacial syndrome may have genetically determined differences in brain
      anatomy that predispose to the development of schizophrenia. OBJECTIVE: To
      determine whether there are differences in brain structure between subjects with
      velocardiofacial syndrome with and without schizophrenia. DESIGN: A cross
      sectional quantitative structural magnetic resonance imaging study in 39 adult
      subjects. SETTING: Referrals were made through medical genetics clinics and
      psychiatric services throughout the United Kingdom. PARTICIPANTS: Thirteen
      subjects with velocardiofacial syndrome and schizophrenia, 12 with
      velocardiofacial syndrome without history of a psychosis, and 14 healthy controls
      volunteered to participate after screening for eligibility. MAIN OUTCOME
      MEASURES: Total and regional brain volumes were analyzed by means of manual
      tracing, and gray- and white-matter densities were obtained by computerized voxel
      based methods. RESULTS: People with velocardiofacial syndrome and schizophrenia,
      compared with both controls and nonschizophrenic patients with velocardiofacial
      syndrome, had a significant (P<.05) reduction in volume of whole-brain (white +
      gray) matter and whole-brain white matter, and an increase in total and sulcal
      cerebrospinal fluid volume. Both velocardiofacial syndrome groups had a reduced
      cerebellar volume compared with controls. CONCLUSIONS: Within velocardiofacial
      syndrome, schizophrenia is associated with generalized differences in brain
      anatomy, but white matter may be particularly implicated. Studies with larger
      samples are needed to replicate our findings.

PMID- 15520357
TI  - The burden of major depression avoidable by longer-term treatment strategies.
AB  - BACKGROUND: Major depression is the largest single cause of nonfatal disease
      burden in Australia. Effective drug and psychological treatments exist, yet are
      underused. OBJECTIVE: To quantify the burden of disease currently averted in
      people seeking care for major depression and the amount of disease burden that
      could be averted in these people under optimal episodic and maintenance treatment
      strategies. DESIGN: Modeling impact of current and optimal treatment strategies
      based on secondary analysis of mental health survey data, studies of the natural
      history of major depression, and meta-analyses of effectiveness data. Monte Carlo
      simulation of uncertainty in the model. SETTING: The cohort of Australian adults
      experiencing an episode of major depression in 2000 are modeled through "what if"
      scenarios of no treatment, current treatment, and optimal treatment strategies
      with cognitive behavioral therapy or antidepressant drug treatment. MAIN OUTCOME
      MEASURE: Disability-Adjusted Life Year. RESULTS: Current episodic treatment
      averts 9% (95% uncertainty interval, 6%-12%) of the disease burden of major
      depression in Australian adults. Optimal episodic treatment with cognitive
      behavioral therapy could avert 28% (95% uncertainty interval, 19%-39%) of this
      disease burden, and with drugs 24% (95% uncertainty interval, 19%-30%) could be
      averted. During the 5 years after an episode of major depression, current
      episodic treatment patterns would avert 13% (95% uncertainty interval, 10%-17%)
      of Disability-Adjusted Life Years, whereas maintenance drug treatment could avert
      50% (95% uncertainty interval, 40%-60%) and maintenance cognitive behavioral
      therapy could avert 52% (95% uncertainty interval, 42%-64%), even if adherence of
      around 60% is taken into account. CONCLUSIONS: Longer-term maintenance drug or
      psychological treatment strategies are required to make significant inroads into
      the large disease burden associated with major depression in the Australian
      population.

PMID- 15520358
TI  - Nicotine dependence and psychiatric disorders in the United States: results from
      the national epidemiologic survey on alcohol and related conditions.
AB  - BACKGROUND: No information is available on the co-occurrence of DSM-IV nicotine
      dependence and Axis I and II psychiatric disorders in the US population.
      OBJECTIVES: To present national data on the co-occurrence of current DSM-IV
      nicotine dependence and other psychiatric disorders by sex and to estimate the
      burden of all US tobacco consumption carried by nicotine-dependent and
      psychiatrically ill individuals. DESIGN: Face-to-face interviews. SETTING: The
      United States. PARTICIPANTS: Household and group-quarters adults (N = 43 093).
      MAIN OUTCOME MEASURES: Prevalence and comorbidity of current nicotine dependence
      and Axis I and II disorders and the percentage of cigarettes consumed in the
      United States among psychiatrically vulnerable subgroups. RESULTS: Among US
      adults, 12.8% (95% confidence interval, 12.0-13.6) were nicotine dependent.
      Associations between nicotine dependence and specific Axis I and II disorders
      were all strong and statistically significant (P<.05) in the total population and
      among men and women. Nicotine-dependent individuals made up only 12.8% (95%
      confidence interval, 12.0-13.6) of the population yet consumed 57.5% of all
      cigarettes smoked in the United States. Nicotine-dependent individuals with a
      comorbid psychiatric disorder made up 7.1% (95% confidence interval, 6.6-7.6) of
      the population yet consumed 34.2% of all cigarettes smoked in the United States.
      CONCLUSIONS: Nicotine-dependent and psychiatrically ill individuals consume about
      70% of all cigarettes smoked in the United States. The results of this study
      highlight the importance of focusing smoking cessation efforts on individuals who
      are nicotine dependent, individuals who have psychiatric disorders, and
      individuals who have comorbid nicotine dependence and other psychiatric
      disorders. Further, awareness of industry segmentation strategies can improve
      smoking cessation efforts of clinicians and other health professionals among all
      smokers and especially among the most vulnerable.

PMID- 15520359
TI  - Psychiatric correlates of gambling in adolescents and young adults grouped by age
      at gambling onset.
AB  - BACKGROUND: Gambling is a prevalent behavior, yet few studies have investigated
      its mental health correlates. Although early-onset engagement in behaviors with
      addictive potential has generally been associated with more severe problems,
      direct investigation of a nationally representative sample of gamblers grouped by
      age at onset of gambling has not been performed. OBJECTIVE: To identify
      differences in psychiatric correlates of gambling and gambling-related attitudes
      and behaviors in adolescents (aged 16-17 years) and in young adults (aged 18-29
      years) with early-onset (before age 18 years) and adult-onset gambling. DESIGN:
      Logistic regression analysis. SETTING: Public access data set derived from random
      digit-dialing telephone surveys. PATIENTS: The study analyzed data from
      adolescent (n = 235), early-onset adult (n = 151), and adult-onset (n = 204) past
      year gamblers and adolescent (n = 299) and adult (n = 187) nongamblers in the
      Gambling Impact and Behavior Study. MAIN OUTCOME MEASURES: Gamblers and
      nongamblers were compared within each group on measures of sociodemographics and
      psychiatric health. Adolescent, early-onset adult, and adult-onset past-year
      gamblers were compared on measures of gambling attitudes and behaviors. RESULTS:
      Adolescent gamblers were more likely than adolescent nongamblers to report
      alcohol and drug use and abuse/dependence and depression. Elevated rates of
      alcohol and drug use and abuse/dependence were observed in early-onset adult
      gamblers vs adult nongamblers, and only elevated rates of alcohol use were
      observed in adult-onset gamblers vs adult nongamblers. Substantial differences in
      reasons for and patterns of gambling were observed among the 3 groups of
      gamblers. CONCLUSIONS: Adolescent-onset gambling is associated with more severe
      psychiatric problems, particularly substance use disorders, in adolescents and
      young adults. More research is needed to investigate the relationships and inform
      prevention and treatment strategies.

PMID- 15520360
TI  - Dispositional optimism and all-cause and cardiovascular mortality in a
      prospective cohort of elderly dutch men and women.
AB  - BACKGROUND: Major depression is known to be related to higher cardiovascular
      mortality. However, epidemiological data regarding dispositional optimism in
      relation to mortality are scanty. OBJECTIVE: To test whether subjects who are
      optimistic live longer than those who are pessimistic. DESIGN: Our analysis
      formed part of a prospective population-based cohort study in the Netherlands
      (Arnhem Elderly Study). SETTING: General community. PARTICIPANTS: Elderly
      subjects aged 65 to 85 years (999 men and women) completed the 30-item validated
      Dutch Scale of Subjective Well-being for Older Persons, with 5 subscales: health,
      self-respect, morale, optimism, and contacts. A total of 941 subjects (466 men
      and 475 women) had complete dispositional optimism data, and these subjects were
      divided into quartiles. MAIN OUTCOME MEASURE: Number of deaths during the follow
      up period. RESULTS: During the follow-up period of 9.1 years (1991-2001), there
      were 397 deaths. Compared with subjects with a high level of pessimism, those
      reporting a high level of optimism had an age- and sex-adjusted hazard ratio of
      0.55 (95% confidence interval, 0.42-0.74; upper vs lower quartile) for all-cause
      mortality. For cardiovascular mortality, the hazard ratio was 0.23 (95%
      confidence interval, 0.10-0.55) when adjusted for age, sex, chronic disease,
      education, smoking, alcohol consumption, history of cardiovascular disease or
      hypertension, body mass index, and total cholesterol level. Protective trend
      relationships were observed between the level of optimism and all-cause and
      cardiovascular mortality (P<.001 and P = .001 for trend, respectively).
      Interaction with sex (P = .04) supported a stronger protective effect of optimism
      in men than women for all-cause mortality but not for cardiovascular mortality.
      CONCLUSIONS: Our results provide support for a graded and independent protective
      relationship between dispositional optimism and all-cause mortality in old age.
      Prevention of cardiovascular mortality accounted for much of the effect.

PMID- 15520361
TI  - Cognitive enhancers as adjuncts to psychotherapy: use of D-cycloserine in phobic
      individuals to facilitate extinction of fear.
AB  - BACKGROUND: Traditional pharmacological approaches to treating psychiatric
      disorders focus on correcting presumed biochemical abnormalities. However, some
      disorders, particularly the anxiety-related disorders exemplified by specific
      phobia, have an emotional learning component to them that can be facilitated with
      psychotherapy. OBJECTIVE: To determine whether D-cycloserine (DCS), a partial
      agonist at the N-methyl-d-aspartate receptor that has previously been shown to
      improve extinction of fear in rodents, will also improve extinction of fear in
      human phobic patients undergoing behavioral exposure therapy. DESIGN: Randomized,
      double-blind, placebo-controlled trial examining DCS vs placebo treatment in
      combination with a precisely controlled exposure paradigm. SETTING: Participants
      were recruited from the general community to a research clinic. PARTICIPANTS:
      Twenty-eight subjects with acrophobia diagnosed by the Structured Clinical
      Interview for DSM-IV were enrolled. INTERVENTIONS: After we obtained pretreatment
      measures of fear, subjects were treated with 2 sessions of behavioral exposure
      therapy using virtual reality exposure to heights within a virtual glass
      elevator. Single doses of placebo or DCS were taken prior to each of the 2
      sessions of virtual reality exposure therapy. Subjects, therapists, and assessors
      were blind to the treatment condition. Subjects returned at 1 week and 3 months
      posttreatment for measures to determine the presence and severity of acrophobia
      symptoms. MAIN OUTCOME MEASURES: Included were measures of acrophobia within the
      virtual environment, measures of acrophobia in the real world, and general
      measures of overall improvement. An objective measure of fear, electrodermal skin
      fluctuation, was also included during the virtual exposure to heights. Symptoms
      were assessed by self-report and by independent assessors at approximately 1 week
      and 3 months posttreatment. RESULTS: Exposure therapy combined with DCS resulted
      in significantly larger reductions of acrophobia symptoms on all main outcome
      measures. Subjects receiving DCS had significantly more improvement compared with
      subjects receiving placebo within the virtual environment (1 week after
      treatment, P</=.001; 3 months later, P</=.05). Subjects receiving DCS also showed
      significantly greater decreases in posttreatment skin conductance fluctuations
      during the virtual exposure (P</=.05). Additionally, subjects receiving DCS had
      significantly greater improvement compared with subjects receiving placebo on
      general measures of real-world acrophobia symptoms (acrophobia avoidance
      [P</=.02], acrophobia anxiety [P</=.01], attitudes toward heights [P</=.04],
      clinical global improvement [P</=.01], and number of self-exposures to real-world
      heights [P</=.01]); the improvement was evident early in treatment and was
      maintained at 3 months. CONCLUSION: These pilot data provide initial support for
      the use of acute dosing of DCS as an adjunct to exposure-based psychotherapy to
      accelerate the associative learning processes that contribute to correcting
      psychopathology.

PMID- 15520362
TI  - Interaction between serotonin transporter gene variation and rearing condition in
      alcohol preference and consumption in female primates.
AB  - BACKGROUND: Serotonin neurotransmission and limbic-hypothalamic-pituitary-adrenal
      (LHPA) axis hormones are thought to be involved in the reinforcement of alcohol
      intake and contribute to the risk for alcoholism. In humans and macaques, a
      promoter polymorphism that decreases transcription of the serotonin transporter
      gene is associated with anxiety and altered LHPA-axis responses to stress, and in
      female macaques, exposure to early-life stress alters LHPA-axis activation in
      response to alcohol. We wanted to determine whether serotonin transporter gene
      promoter variation (rh-5HTTLPR) and rearing condition would interact to influence
      alcohol preference in female rhesus macaques. Because of the involvement of
      stress and LHPA-axis activity in symptoms of withdrawal and relapse, we also
      wanted to determine whether serotonin transporter gene variation and rearing
      condition would influence changes in the patterns of alcohol consumption across a
      6-week alcohol consumption paradigm. METHODS: Female macaques were reared with
      their mothers in social groups (n = 18) or in peer-only groups (n = 14). As young
      adults, they were given access to an aspartame-sweetened 8.4% alcohol solution
      and vehicle for 1 hour per day, and volumes of consumption of alcoholic and
      nonalcoholic solutions were recorded. Serotonin transporter genotype (l/l and
      l/s) was determined using polymerase chain reaction followed by gel
      electrophoresis. RESULTS: We found interactions between rearing condition and
      serotonin transporter genotype, such that l/s peer-reared females demonstrated
      higher levels of ethanol preference. We also found an effect of rearing condition
      on the percentage change in alcohol consumed during the 6 weeks as well as a
      phase by rearing interaction, such that peer-reared animals progressively
      increased their levels of consumption across the course of the study. This was
      especially evident for peer-reared females with the l/s rh5-HTTLPR genotype.
      CONCLUSION: These data suggest a potential interaction between serotonin
      transporter gene variation and early experience in vulnerability to alcoholism.

PMID- 15520363
TI  - A multicenter, randomized, double-blind, placebo-controlled trial of paroxetine
      in children and adolescents with social anxiety disorder.
AB  - BACKGROUND: Social anxiety disorder is a debilitating, highly prevalent disorder
      in children and adolescents. If left untreated, it can interfere with emotional,
      social, and school functioning. OBJECTIVE: To evaluate the efficacy and
      tolerability of paroxetine in children and adolescents with social anxiety
      disorder. DESIGN AND SETTING: Multicenter, 16-week, randomized, double-blind,
      placebo-controlled, flexible-dose, parallel-group, outpatient study. Patients A
      total of 322 children (8-11 years of age) and adolescents (12-17 years of age)
      with social anxiety disorder as their predominant psychiatric illness.
      Intervention Eligible patients were randomized (1:1) to receive paroxetine (10-50
      mg/d) or placebo. RESULTS: Four hundred twenty-five patients were screened, and
      322 were randomized to treatment. Of these, 319 were included in the intention-to
      treat population (paroxetine, n = 163; placebo, n = 156). At the week 16 last
      observation carried forward end point, the odds of responding (Clinical Global
      Impression-Improvement score of 1 or 2) were statistically significantly greater
      for paroxetine (77.6% response [125/161]) than for placebo (38.3% response
      [59/154]) (adjusted odds ratio, 7.02; 95% confidence interval, 4.07 to 12.11;
      P<.001). The proportion of patients who were "very much" improved (Clinical
      Global Impression-Improvement score of 1) was 47.8% (77/161) for paroxetine
      compared with 14.9% (23/154) for placebo. Adverse events occurring at an
      incidence of 5% or greater for paroxetine and twice that for placebo were
      insomnia (14.1% vs 5.8%), decreased appetite (8.0% vs 3.2%), and vomiting (6.7%
      vs 1.9%). Withdrawals due to adverse events were infrequent (5.5% [9/163] for
      paroxetine and 1.3% [2/156] for placebo). CONCLUSION: Paroxetine is an effective,
      generally well-tolerated treatment for pediatric social anxiety disorder.

PMID- 15520364
TI  - Effects of the serotonin transporter gene promoter polymorphism on mirtazapine
      and paroxetine efficacy and adverse events in geriatric major depression.
AB  - BACKGROUND: The "long/short"polymorphism (5HTTLPR) in the promoter of the
      serotonin transporter gene (SLC6A4) has been proposed as a pharmacogenetic marker
      for antidepressant efficacy. Some but not all studies have found that the short
      form of 5HTTLPR (S allele) results in decreased efficacy of selective serotonin
      reuptake inhibitors. OBJECTIVE: To determine if the 5HTTLPR polymorphism
      influences the efficacy and tolerability of mirtazapine and paroxetine
      hydrochloride, 2 frequently prescribed antidepressants with differing
      pharmacologic profiles, in geriatric depression. DESIGN: Double-blind, randomized
      8-week study. SETTING: Eighteen academic and private outpatient clinics.
      PATIENTS: We evaluated 246 cognitively intact patients 65 years or older with
      major depression. INTERVENTIONS: Antidepressant therapy with 15 to 45 mg/d of
      mirtazapine (n = 124) or 20 to 40 mg/d of paroxetine (n = 122). MAIN OUTCOME
      MEASURES: The Hamilton Depression Rating Scale-17 and Geriatric Depression Scale,
      severity of adverse events and dosing compliance indexes, and discontinuations
      due to adverse events. Outcome measures were stratified according to 5HTTLPR
      genotypes. RESULTS: Geriatric Depression Scale scores indicated that S allele
      carriers treated with paroxetine showed a small impairment in antidepressant
      response. Among mirtazapine-treated patients, there was little indication that
      the 5HTTLPR genotype affected antidepressant efficacy. However, the 5HTTLPR
      polymorphism had a dramatic effect on adverse events. Among paroxetine-treated
      subjects, S allele carriers experienced more severe adverse events during the
      course of the study, achieved significantly lower final daily doses, and had more
      discontinuations at days 14, 21, 28, 42, and 49. Surprisingly, among mirtazapine
      treated subjects, S allele carriers had fewer discontinuations due to adverse
      events, experienced less severe adverse events, and achieved higher final daily
      doses. CONCLUSIONS: These results support the hypothesis that the S allele of
      5HTTLPR at the SLC6A4 locus is associated with a poor outcome after treatment
      with selective serotonin reuptake inhibitors. However, the major effect was on
      the tolerability of these drugs rather than efficacy. Results from mirtazapine
      treated patients indicate that the effect of this polymorphism on outcome may
      depend on the mechanism of antidepressant action.

PMID- 15520365
TI  - Does glial asthenia predispose to schizophrenia?

PMID- 15520366
TI  - Biography of E. P. Greenberg.

PMID- 15520367
TI  - Haploinsufficiency of delta-like 4 ligand results in embryonic lethality due to
      major defects in arterial and vascular development.
AB  - Vascular development depends on the highly coordinated actions of a variety of
      angiogenic regulators, most of which apparently act downstream of vascular
      endothelial growth factor (VEGF). One potential such regulator is delta-like 4
      ligand (Dll4), a recently identified partner for the Notch receptors. We
      generated mice in which the Dll4 gene was replaced with a reporter gene, and
      found that Dll4 expression is initially restricted to large arteries in the
      embryo, whereas in adult mice and tumor models, Dll4 is specifically expressed in
      smaller arteries and microvessels, with a striking break in expression just as
      capillaries merge into venules. Consistent with these arterial-specific
      expression patterns, heterozygous deletion of Dll4 resulted in prominent albeit
      variable defects in arterial development (reminiscent of those in Notch
      knockouts), including abnormal stenosis and atresia of the aorta, defective
      arterial branching from the aorta, and even arterial regression, with occasional
      extension of the defects to the venous circulation; also noted was gross
      enlargement of the pericardial sac and failure to remodel the yolk sac
      vasculature. These striking phenotypes resulting from heterozygous deletion of
      Dll4 indicate that vascular development may be as sensitive to subtle changes in
      Dll4 dosage as it is to subtle changes in VEGF dosage, because VEGF accounts for
      the only other example of haploid insufficiency, resulting in obvious vascular
      abnormalities. In summary, Dll4 appears to be a major trigger of Notch receptor
      activities previously implicated in arterial and vascular development, and it may
      represent a new opportunity for pro- and anti-angiogenic therapies.

PMID- 15520369
TI  - A polymer library approach to suicide gene therapy for cancer.
AB  - Optimal gene therapy for cancer must (i) deliver DNA to tumor cells with high
      efficiency, (ii) induce minimal toxicity, and (iii) avoid gene expression in
      healthy tissues. To this end, we generated a library of >500 degradable,
      poly(beta-amino esters) for potential use as nonviral DNA vectors. Using high
      throughput methods, we screened this library in vitro for transfection efficiency
      and cytotoxicity. We tested the best performing polymer, C32, in mice for
      toxicity and DNA delivery after intratumor and i.m. injection. C32 delivered DNA
      intratumorally approximately 4-fold better than one of the best commercially
      available reagents, jetPEI (polyethyleneimine), and 26-fold better than naked
      DNA. Conversely, the highest transfection levels after i.m. administration were
      achieved with naked DNA, followed by polyethyleneimine; transfection was rarely
      observed with C32. Additionally, polyethyleneimine induced significant local
      toxicity after i.m. injection, whereas C32 demonstrated no toxicity. Finally, we
      used C32 to deliver a DNA construct encoding the A chain of diphtheria toxin (DT
      A) to xenografts derived from LNCaP human prostate cancer cells. This construct
      regulates toxin expression both at the transcriptional level by the use of a
      chimeric-modified enhancer/promoter sequence of the human prostate-specific
      antigen gene and by DNA recombination mediated by Flp recombinase. C32 delivery
      of the A chain of diphtheria toxin DNA to LNCaP xenografts suppressed tumor
      growth and even caused 40% of tumors to regress in size. Because C32 transfects
      tumors locally at high levels, transfects healthy muscle poorly, and displays no
      toxicity, it may provide a vehicle for the local treatment of cancer.

PMID- 15520370
TI  - Multiple rare variants in different genes account for multifactorial inherited
      susceptibility to colorectal adenomas.
AB  - Clear-cut inherited Mendelian traits, such as familial adenomatous polyposis or
      hereditary nonpolyposis colorectal cancer, account for <4% of colorectal cancers.
      Another 20% of all colorectal cancers are thought to occur in individuals with a
      significant inherited multifactorial susceptibility to colorectal cancer that is
      not obviously familial. Incompletely penetrant, comparatively rare missense
      variants in the adenomatous polyposis coli gene, which is responsible for
      familial adenomatous polyposis, have been described in patients with multiple
      colorectal adenomas. These variants represent a category of variation that has
      been suggested, quite generally, to account for a substantial fraction of such
      multifactorial inherited susceptibility. The aim of this study was to explore
      this rare variant hypothesis for multifactorial inheritance by using multiple
      colorectal adenomas as the model. Patients with multiple adenomas were screened
      for germ-line variants in a panel of candidate genes. Germ-line DNA was obtained
      from 124 patients with between 3 and 100 histologically proven synchronous or
      metachronous adenomatous polyps. All patients were tested for the adenomatous
      polyposis coli variants I1307K and E1317Q, and variants were also sought in AXIN1
      (axin), CTNNB1 (beta-catenin), and the mismatch repair genes hMLH1 and hMSH2. The
      control group consisted of 483 random controls. Thirty of 124 (24.9%) patients
      carried potentially pathogenic germ-line variants as compared with 55 (
      approximately 12%) of the controls. This overall difference is highly
      significant, suggesting that many rare variants collectively contribute to the
      inherited susceptibility to colorectal adenomas.

PMID- 15520371
TI  - Identification of hair cycle-associated genes from time-course gene expression
      profile data by using replicate variance.
AB  - The hair-growth cycle is an example of a cyclic process that is well
      characterized morphologically but understood incompletely at the molecular level.
      As an initial step in discovering regulators in hair-follicle morphogenesis and
      cycling, we used DNA microarrays to profile mRNA expression in mouse back skin
      from eight representative time points. We developed a statistical algorithm to
      identify the set of genes expressed within skin that are associated specifically
      with the hair-growth cycle. The methodology takes advantage of higher replicate
      variance during asynchronous hair cycles in comparison with synchronous cycles.
      More than one-third of genes with detectable skin expression showed hair-cycle
      related changes in expression, suggesting that many more genes may be associated
      with the hair-growth cycle than have been identified in the literature. By using
      a probabilistic clustering algorithm for replicated measurements, these genes
      were grouped into 30 time-course profile clusters, which fall into four major
      classes. Distinct genetic pathways were characteristic for the different time
      course profile clusters, providing insights into the regulation of hair-follicle
      cycling and suggesting that this approach is useful for identifying hair follicle
      regulators. In addition to revealing known hair-related genes, we identified
      genes that were not previously known to be hair cycle-associated and confirmed
      their temporal and spatial expression patterns during the hair-growth cycle by
      quantitative real-time PCR and in situ hybridization. The same computational
      approach should be generally useful for identifying genes associated with cyclic
      processes from complex tissues.

PMID- 15520372
TI  - Computational modeling reveals how interplay between components of a GTPase-cycle
      module regulates signal transduction.
AB  - Heterotrimeric G protein signaling is regulated by signaling modules composed of
      heterotrimeric G proteins, active G protein-coupled receptors (Rs), which
      activate G proteins, and GTPase-activating proteins (GAPs), which deactivate G
      proteins. We term these modules GTPase-cycle modules. The local concentrations of
      these proteins are spatially regulated between plasma membrane microdomains and
      between the plasma membrane and cytosol, but no data or models are available that
      quantitatively explain the effect of such regulation on signaling. We present a
      computational model of the GTPase-cycle module that predicts that the interplay
      of local G protein, R, and GAP concentrations gives rise to 16 distinct signaling
      regimes and numerous intermediate signaling phenomena. The regimes suggest
      alternative modes of the GTPase-cycle module that occur based on defined local
      concentrations of the component proteins. In one mode, signaling occurs while G
      protein and receptor are unclustered and GAP eliminates signaling; in another, G
      protein and receptor are clustered and GAP can rapidly modulate signaling but
      does not eliminate it. Experimental data from multiple GTPase-cycle modules is
      interpreted in light of these predictions. The latter mode explains previously
      paradoxical data in which GAP does not alter maximal current amplitude of G
      protein-activated ion channels, but hastens signaling. The predictions indicate
      how variations in local concentrations of the component proteins create GTPase
      cycle modules with distinctive phenotypes. They provide a quantitative framework
      for investigating how regulation of local concentrations of components of the
      GTPase-cycle module affects signaling.

PMID- 15520368
TI  - Hematopoietic gene expression profile in zebrafish kidney marrow.
AB  - The zebrafish kidney marrow is considered to be the organ of definitive
      hematopoiesis, analogous to the mammalian bone marrow. We have sequenced 26,143
      ESTs and isolated 304 cDNAs with putative full-length ORF from a zebrafish kidney
      marrow cDNA library. The ESTs formed 7,742 assemblies, representing both
      previously identified zebrafish ESTs (56%) and recently discovered zebrafish ESTs
      (44%). About 30% of these EST assemblies have orthologues in humans, including
      1,282 disease-associated genes in the Online Mendelian Inheritance in Man (OMIM)
      database. Comparison of the effective and regulatory molecules related to
      erythroid functions across species suggests a good conservation from zebrafish to
      human. Interestingly, both embryonic and adult zebrafish globin genes showed
      higher homology to the human embryonic globin genes than to the human fetal/adult
      ones, consistent with evo-devo correlation hypothesis. In addition, conservation
      of a whole set of transcription factors involved in globin gene switch suggests
      the regulatory network for such remodeling mechanism existed before the
      divergence of the teleost and the ancestor of mammals. We also carried out whole
      mount mRNA in situ hybridization assays for 493 cDNAs and identified 80 genes
      (16%) with tissue-specific expression during the first five days of zebrafish
      development. Twenty-six of these genes were specifically expressed in
      hematopoietic or vascular tissues, including three previously unidentified
      zebrafish genes: coro1a, nephrosin, and dab2. Our results indicate that conserved
      genetic programs regulate vertebrate hematopoiesis and vasculogenesis, and
      support the role of the zebrafish as an important animal model for studying both
      normal development and the molecular pathogenesis of human blood diseases.

PMID- 15520373
TI  - Age-related reduction in microcolumnar structure in area 46 of the rhesus monkey
      correlates with behavioral decline.
AB  - Many age-related declines in cognitive function are attributed to the prefrontal
      cortex, area 46 being especially critical. Yet in normal aging, studies indicate
      that neurons are not lost in area 46, suggesting that impairments result from
      more subtle processes. One cortical feature that is functionally important, but
      that has not been examined in normal aging because of a lack of efficient
      quantitative methods, is the vertical arrangement of neurons into microcolumns, a
      fundamental computational unit of the cortex. By using a density-map method
      derived from condensed-matter physics, we quantified microcolumns in area 46 of
      seven young and seven aged rhesus monkeys that had been cognitively tested. This
      analysis demonstrated that there is no age-related reduction in total neuronal
      density or in microcolumn width, length, or periodicity. There was, however, a
      statistically significant decrease in the strength of microcolumns, indicating
      microcolumnar disorganization. This reduction in strength was significantly
      correlated with age-related cognitive decline on tests of spatial working memory
      and recognition memory independent of the effect of age. Modeling demonstrated
      that random neuron displacements of approximately 30% of a neuronal diameter (<3
      mum) produced the observed reduction in strength. Hence, it is possible that,
      with changes in dendrites and myelinated axons, subtle displacements of neurons
      occur that alter microcolumnar structure and correlate with age-induced
      dysfunction. Therefore, quantitative measurement of microcolumnar structure may
      provide a sensitive morphological method to assay microcolumnar function in aging
      and other conditions.

PMID- 15520374
TI  - Inorganic polyphosphate in the origin and survival of species.
AB  - Inorganic polyphosphate (poly P), in chains of tens to hundreds of phosphate
      residues, linked by high-energy bonds, is environmentally ubiquitous and
      abundant. In prebiotic evolution it could have provided a flexible, polyanionic
      scaffold to assemble macromolecules. It has been conserved in every cell in
      nature. In prokaryotes, a major poly P synthetic enzyme is poly P kinase 1
      (PPK1), which is found in 100 bacterial genomes, including numerous pathogens.
      Null mutants of PPK1, with low poly P levels, are defective in survival: namely,
      they show defective responses to physical/chemical stresses and predation.
      Pathogens with a PPK1 deletion are defective in biofilm formation, quorum
      sensing, general stress and stringent responses, motility, and other virulence
      properties. With the exception of Dictyostelium, PPK1 is absent in eukaryotes and
      provides a novel target for chemotherapy that would affect both virulence and
      susceptibility to antibacterial compounds. Remarkably, another PPK in
      Dictyostelium discoideum (PPK2) is an actin-related protein (Arp) complex that is
      polymerized into an actin-like filament, concurrent with its reversible synthesis
      of a poly P chain from ATP.

PMID- 15520375
TI  - Essential role of membrane-attack protein in malarial transmission to mosquito
      host.
AB  - After ingestion of infected blood by a mosquito, malarial parasites are
      fertilized in the mosquito midgut and develop into motile ookinetes. These
      ookinetes invade epithelial cells by rupturing the cell membrane and migrate
      through the cytoplasm toward the basal lamina, on which they develop to oocysts.
      Here we report that a microneme protein with a membrane-attack complex and
      perforin (MACPF)-related domain, which we name membrane-attack ookinete protein
      (MAOP), is produced in the ookinete stage and plays an essential role in midgut
      invasion by the ookinete. Ookinetes with the MAOP gene disrupted completely lost
      infectivity to the midgut. After ingestion of blood infected with the disrupted
      parasite, the midgut epithelium remained intact, making a clear contrast with the
      damaged midgut epithelium invaded by wild-type ookinetes. Electron microscopic
      analysis showed that the disruptant ookinetes migrate to the gut epithelium and
      attach to the cell surface at the apical tip, but are unable to enter the
      cytoplasm by rupturing the cell membrane. These results indicate that the MAOP
      molecule acts on the plasma membrane of the host-cell-like mammalian MACPF family
      proteins that create pores in the membrane of target cells. Another previously
      identified MACPF-related molecule is produced in the liver-infective sporozoite
      and has a crucial role in traversing the liver sinusoidal cell boundary. The
      present finding, thus, suggests that conserved mechanisms for membrane rupture
      involving MACPF-related proteins are used in different host invasive stages of
      the malarial parasite, playing a key role in breaching biological barriers of
      host organs.

PMID- 15520376
TI  - Antitumor polyketide biosynthesis by an uncultivated bacterial symbiont of the
      marine sponge Theonella swinhoei.
AB  - Bacterial symbionts have long been suspected to be the true producers of many
      drug candidates isolated from marine invertebrates. Sponges, the most important
      marine source of biologically active natural products, have been frequently
      hypothesized to contain compounds of bacterial origin. This symbiont hypothesis,
      however, remained unproven because of a general inability to cultivate the
      suspected producers. However, we have recently identified an uncultured
      Pseudomonas sp. symbiont as the most likely producer of the defensive antitumor
      polyketide pederin in Paederus fuscipes beetles by cloning the putative
      biosynthesis genes. Here we report closely related genes isolated from the highly
      complex metagenome of the marine sponge Theonella swinhoei, which is the source
      of the onnamides and theopederins, a group of polyketides that structurally
      resemble pederin. Sequence features of the isolated genes clearly indicate that
      it belongs to a prokaryotic genome and should be responsible for the biosynthesis
      of almost the entire portion of the polyketide structure that is correlated with
      antitumor activity. Besides providing further proof for the role of the related
      beetle symbiont-derived genes, these findings raise intriguing ecological and
      evolutionary questions and have important general implications for the
      sustainable production of otherwise inaccessible marine drugs by using
      biotechnological strategies.

PMID- 15520377
TI  - Transition state and encounter complex for fast association of cytochrome c2 with
      bacterial reaction center.
AB  - Electrostatic interactions strongly enhance the electron transfer reaction
      between cytochrome (Cyt) c(2) and reaction center (RC) from photosynthetic
      bacteria, yielding a second-order rate constant, k(2) approximately 10(9) s(
      1).M(-1), close to the diffusion limit. The proposed mechanism involves an
      encounter complex (EC) stabilized by electrostatic interactions, followed by a
      transition state (TS), leading to the bound complex active in electron transfer.
      The effect of electrostatic interactions was previously studied by Tetreault et
      al. [Tetreault, M., Cusanovich, M., Meyer, T., Axelrod, H. & Okamura, M. Y.
      (2002) Biochemistry 41, 5807-5815] by measuring k(2) for RC and Cyt molecules
      with modified charged residues at the binding interface. The present work is a
      computational analysis of this kinetic study to determine the ensemble of
      configurations of the TS and EC. Changes in the TS energies due to different
      mutations were compared with differences in the calculated electrostatic energies
      for a wide range of Cyt/RC configurations. The TS ensemble, obtained from
      structures having the highest correlation coefficients in the comparison with
      experimental data, has the Cyt displaced by approximately 10 A from its position
      in x-ray crystal structure, close to the average position of the EC ensemble,
      with strong electrostatic interactions between Cyt on the M subunit side of the
      RC surface. The heme of the Cyt is oriented toward Tyr L162 on the RC, the
      tunneling contact in the bound final state on the RC. The similarity between the
      structures of the EC, TS, and bound state can account for the rapid rate of
      association responsible for fast diffusion-controlled electron transfer.

PMID- 15520378
TI  - Different functions of HetR, a master regulator of heterocyst differentiation in
      Anabaena sp. PCC 7120, can be separated by mutation.
AB  - The HetR protein has long been recognized as a key player in the regulation of
      heterocyst development. HetR is known to possess autoproteolytic and DNA-binding
      activities. During a search for mutants of Anabaena sp. PCC 7120 that can
      overcome heterocyst suppression caused by overexpression of the patS gene, which
      encodes a negative regulator of differentiation, a bypass mutant strain, S2-45,
      was isolated that produced a defective pattern (Pat phenotype) of irregularly
      spaced single and multiple contiguous heterocysts (Mch phenotype) in combined
      nitrogen-free medium. Analysis of the S2-45 mutant revealed a R223W mutation in
      HetR, and reconstruction in the wild-type background showed that this mutation
      was responsible for the Mch phenotype and resistance not only to overexpressed
      patS, but also to overexpressed hetN, another negative regulator of
      differentiation. Ectopic overexpression of the hetRR223W allele in the hetRR223W
      background resulted in a conditionally lethal (complete differentiation)
      phenotype. Analysis of the heterocyst pattern in the hetRR223W mutant revealed
      that heterocysts differentiate essentially randomly along filaments, indicating
      that this mutation results in an active protein that is insensitive to the major
      signals governing heterocyst pattern formation. These data provide genetic
      evidence that, apart from being an essential activator of differentiation, HetR
      plays a central role in the signaling pathway that controls the heterocyst
      pattern.

PMID- 15520379
TI  - An unusual tryptophanyl tRNA synthetase interacts with nitric oxide synthase in
      Deinococcus radiodurans.
AB  - In mammals, nitric oxide synthases (NOSs) produce nitric oxide for signaling and
      defense functions; in Streptomyces, NOS proteins nitrate a tryptophanyl moiety in
      synthesis of a phytotoxin. We have discovered that the NOS protein from the
      radiation-resistant bacterium Deinococcus radiodurans (deiNOS) associates with an
      unusual tryptophanyl tRNA synthetase (TrpRS). D. radiodurans contains genes for
      two TrpRSs: the first has approximately 40% sequence identity to typical TrpRSs,
      whereas the second, identified as the NOS-interacting protein (TrpRS II), has
      only approximately 29% identity. TrpRS II is induced after radiation damage and
      contains an N-terminal extension similar to those of proteins involved in stress
      responses. Recombinantly expressed TrpRS II binds tryptophan (Trp), ATP, and D.
      radiodurans tRNA(Trp) and catalyzes the formation of 5' adenyl-Trp and tRNA(Trp),
      with approximately five times less activity than TrpRS I. Upon coexpression in
      Escherichia coli, TrpRS II binds to, copurifies with, and dramatically enhances
      the solubility of deiNOS. Dimeric TrpRS II binds dimeric deiNOS with a
      stoichiometry of 1:1 and a dissociation constant of 6-30 muM. Upon forming a
      complex, deiNOS quenches the fluorescence of an ATP analog bound to TrpRS II, and
      increases its affinity for substrate l-arginine. Remarkably, TrpRS II also
      activates the NOS activity of deiNOS. These findings reveal a link between
      bacterial NOS and Trp metabolism in a second organism and may indicate yet
      another novel biological function for bacterial NOS.

PMID- 15520380
TI  - Atomic structure of a tryptophan-zipper pentamer.
AB  - Coiled-coil motifs are ubiquitous mediators of specific protein-protein
      interactions through the formation of interlocking hydrophobic seams between
      alpha-helical chains. Residues that form these seams occur at the first (a) and
      fourth (d) positions of a characteristic 7-aa repeat and are primarily aliphatic.
      The potential of aromatic residues to promote helix association in a coiled coil
      was explored by engineering a "Trp-zipper" protein with Trp residues at all 14 a
      and d positions. The protein forms a discrete, stable, alpha-helical pentamer in
      water at physiological pH. Its 1.45-A crystal structure reveals a parallel, five
      stranded coiled coil, a previously uncharacterized type of "knobs-into-holes"
      packing interaction between interfacial Trp side chains, and an unusual
      approximately 8-A-diameter axial channel lined with indole rings that is filled
      with polyethylene glycol 400 and water and sulfate ion molecules. The engineered
      Trp-zipper pentamer enlarges current views of coiled-coil assembly, molecular
      recognition, and protein engineering, and may serve as a soluble model for
      membrane ion channels.

PMID- 15520381
TI  - The regulated long-term delivery of therapeutic proteins by using antigen
      specific B lymphocytes.
AB  - Memory lymphocytes are important mediators of the immune response. These cells
      are long-lived and undergo clonal expansion upon reexposure to specific antigen,
      differentiating into effector cells that secrete Ig or cytokines while
      maintaining a residual pool of memory T and B lymphocytes. Here, the ability of
      antigen-specific lymphocytes to undergo repeated cycles of antigen-driven clonal
      expansion and contraction is exploited in a therapeutic protocol aimed at
      regulating protein delivery. The principle of this strategy is to introduce genes
      encoding proteins of therapeutic interest into a small number of antigen-specific
      B lymphocytes. Output of therapeutic protein can then be regulated in vivo by
      manipulating the size of the responder population by antigen challenge. To
      evaluate whether such an approach is feasible, we developed a mouse model system
      in which Emu- and Iglambda-based vectors were used to express human
      erythropoietin (hEPO) gene in B lymphocytes. These mice were then immunized with
      the model antigen phycoerythrin (PE), and immune splenocytes (or purified PE
      specific B lymphocytes) were adoptively transferred to normal or mutant (EPO
      deficient) hosts. High levels of hEPO were detected in the serum of adoptively
      transferred normal mice after PE administration, and this responsiveness was
      maintained for several months. Similarly, in EPO-deficient anemic recipients,
      antigen-driven hEPO expression was shown to restore hematocrit levels to normal.
      These results show that antigen-mediated regulation of memory lymphocytes can be
      used as a strategy for delivering therapeutic proteins in vivo.

PMID- 15520382
TI  - Chicken W: a genetically uniform chromosome in a highly variable genome.
AB  - The Y chromosome of organisms with male heterogamety is expected to show reduced
      levels of genetic diversity, because the effective population size is one-fourth
      that of autosomes. However, studies in mammals, flies, and plants show that Y
      chromosome diversity is lower than expected even when differences in effective
      population size are taken into account. This may be explained by skewed
      reproductive success among males, leading to low male effective population size,
      or by a strong role of selection in shaping levels of nucleotide diversity in
      nonrecombining chromosomes. We tested these hypotheses in a system with female
      heterogamety by estimating nucleotide diversity in the female-specific W
      chromosome of the domestic chicken by resequencing of 7,643 base pairs in 47
      birds from 10 highly divergent breeds. The screening revealed only one single
      segregating site, which is in sharp contrast to our previous observation, using a
      similar panel of birds of, on average, one segregating site every 39 base pairs
      in autosomal sequence. When taking sex-specific mutation rates and differences in
      effective population size into account, the observed degree of W chromosome
      polymorphism is 28-fold lower than expected for the frequency of segregating
      sites and 13-fold lower than expected for estimates of nucleotide diversity
      (autosomes, 6.5 x 10(-3); W, 7.0 x 10(-5)). We note that selection is the only
      factor that can explain the reduced diversity in the sex-limited chromosome
      irrespective of mode of reproduction or whether there is male or female
      heterogamety. Reduced variability in female-specific W chromosomes is not easily
      explained by sexual selection.

PMID- 15520383
TI  - Neuronal Shp2 tyrosine phosphatase controls energy balance and metabolism.
AB  - Shp2, a Src homology 2-containing tyrosine phosphatase, has been implicated in a
      variety of growth factor or cytokine signaling pathways. However, it is
      conceivable that this enzyme acts predominantly in one pathway versus the others
      in a cell, depending on the cellular context. To determine the putative functions
      of Shp2 in the adult brain, we selectively deleted Shp2 in postmitotic forebrain
      neurons by crossing CaMKIIalpha-Cre transgenic mice with a conditional Shp2
      mutant (Shp2(flox)) strain. Surprisingly, a prominent phenotype of the mutant
      (CaMKIIalpha-Cre:Shp2(flox/flox) or CaSKO) mice was the development of early
      onset obesity, with increased serum levels of leptin, insulin, glucose, and
      triglycerides. The mutant mice were not hyperphagic but developed enlarged and
      steatotic liver. Consistent with previous in vitro data, we found that Shp2 down
      regulates Jak2/Stat3 (signal transducer and activator of transcription 3)
      activation by leptin in the hypothalamus. However, Jak2/Stat3 down-regulation is
      offset by a dominant Shp2 promotion of the leptin-stimulated Erk pathway, leading
      to induction rather than suppression of leptin resistance upon Shp2 deletion in
      the brain. Collectively, these results suggest that a primary function of Shp2 in
      postmitotic forebrain neurons is to control energy balance and metabolism, and
      that this phosphatase is a critical signaling component of leptin receptor ObRb
      in the hypothalamus. Shp2 shows potential as a neuronal target for pharmaceutical
      sensitization of obese patients to leptin action.

PMID- 15520384
TI  - Sir2 mediates longevity in the fly through a pathway related to calorie
      restriction.
AB  - Calorie restriction can extend life span in a variety of species including
      mammals, flies, nematodes, and yeast. Despite the importance of this nearly
      universal effect, little is understood about the molecular mechanisms that
      mediate the life-span-extending effect of calorie restriction in metazoans. Sir2
      is known to be involved in life span determination and calorie restriction in
      yeast mother cells. In nematodes increased Sir2 can extend life span, but a
      direct link to calorie restriction has not been demonstrated. We now report that
      Sir2 is directly involved in the calorie-restriction life-span-extending pathway
      in Drosophila. We demonstrate that an increase in Drosophila Sir2 (dSir2) extends
      life span, whereas a decrease in dSir2 blocks the life-span-extending effect of
      calorie reduction or rpd3 mutations. These data lead us to propose a genetic
      pathway by which calorie restriction extends life span and provides a framework
      for genetic and pharmacological studies of life span extension in metazoans.

PMID- 15520385
TI  - Dopamine transporters depolarize neurons by a channel mechanism.
AB  - Neurotransmitter transporters generate larger currents than expected if one
      assumes fixed stoichiometry models. It remains controversial, however, whether
      these depolarizing currents arise from high density and rapid turnover rates of a
      classical transporter, or whether transporters exhibit bona fide channel
      behavior. Although heterologously expressed transporters show single-channel
      behavior and noise analysis in native cells strongly suggests channel behavior,
      no directly observed single-channel events associated with transporters have been
      reported thus far in native cells. We describe single-channel events arising
      directly from the Caenorhabditis elegans dopamine transporter (DAT-1) as
      evidenced by DA-induced channel activity blocked by a high-affinity DAT-1
      inhibitor, increased channel activity in neurons that overexpress DAT-1, and loss
      of channels in dat-1 knockout neurons. Our data indicate that authentic
      transporter channels underlie depolarizing whole-cell currents. Thus, DA
      transporters not only transport DA but also exhibit a channel mode of conduction
      that directly modulates membrane potential and neuronal function.

PMID- 15520386
TI  - Convergent evolution of behavior in an adaptive radiation of Hawaiian web
      building spiders.
AB  - Species in ecologically similar habitats often display patterns of divergence
      that are strikingly comparable, suggesting that natural selection can lead to
      predictable evolutionary change in communities. However, the relative importance
      of selection as an agent mediating in situ diversification, versus dispersal
      between habitats, cannot be addressed without knowledge of phylogenetic history.
      We used an adaptive radiation of spiders within the Hawaiian Islands to test the
      prediction that species of spiders on different islands would independently
      evolve webs with similar architectures. Tetragnatha spiders are the only
      nocturnal orb-weaving spiders endemic to the Hawaiian archipelago, and multiple
      species of orb-weaving Tetragnatha co-occur within mesic and wet forest habitats
      on each of the main islands. Therefore, comparison of web architectures spun by
      spiders on different islands allowed study of replicated evolutionary events of
      past behavioral diversification. We found that species within each island
      construct webs with architectures that differ from one another. However, pairs of
      species on different islands, "ethotypes," share remarkable similarities in web
      architectures. Phylogenetic analysis demonstrated that the species comprising
      these ethotypes evolved independent of one another. Our study illustrates the
      high degree of predictability that can be exhibited by the evolutionary
      diversification of complex behaviors. However, not all web architectures were
      shared between islands, demonstrating that unique effects also have played an
      important role in the historical diversification of behavior.

PMID- 15520387
TI  - Identification of viral genomic elements responsible for rabies virus
      neuroinvasiveness.
AB  - Attenuated tissue culture-adapted and natural street rabies virus (RV) strains
      differ greatly in their neuroinvasiveness. To identify the elements responsible
      for the ability of an RV to enter the CNS from a peripheral site and to cause
      lethal neurological disease, we constructed a full-length cDNA clone of silver
      haired bat-associated RV (SHBRV) strain 18 and exchanged the genes encoding RV
      proteins and genomic sequences of this highly neuroinvasive RV strain with those
      of a highly attenuated nonneuroinvasive RV vaccine strain (SN0). Analysis of the
      recombinant RV (SB0), which was recovered from SHBRV-18 cDNA, indicated that this
      RV is phenotypically indistinguishable from WT SHBRV-18. Characterization of the
      chimeric viruses revealed that in addition to the RV glycoprotein, which plays a
      predominant role in the ability of an RV to invade the CNS from a peripheral
      site, viral elements such as the trailer sequence, the RV polymerase, and the
      pseudogene contribute to RV neuroinvasiveness. Analyses also revealed that
      neuroinvasiveness of an RV correlates inversely with the time necessary for
      internalization of RV virions and with the capacity of the virus to grow in
      neuroblastoma cells.

PMID- 15520388
TI  - Melyrid beetles (Choresine): a putative source for the batrachotoxin alkaloids
      found in poison-dart frogs and toxic passerine birds.
AB  - Batrachotoxins are neurotoxic steroidal alkaloids first isolated from a Colombian
      poison-dart frog and later found in certain passerine birds of New Guinea.
      Neither vertebrate group is thought to produce the toxins de novo, but instead
      they likely sequester them from dietary sources. Here we describe the presence of
      high levels of batrachotoxins in a little-studied group of beetles, genus
      Choresine (family Melyridae). These small beetles and their high toxin
      concentrations suggest that they might provide a toxin source for the New Guinea
      birds. Stomach content analyses of Pitohui birds revealed Choresine beetles in
      the diet, as well as numerous other small beetles and arthropods. The family
      Melyridae is cosmopolitan, and relatives in Colombian rain forests of South
      America could be the source of the batrachotoxins found in the highly toxic
      Phyllobates frogs of that region.

PMID- 15520389
TI  - Uncoupling substrate and activation functions of rotavirus NSP5: phosphorylation
      of Ser-67 by casein kinase 1 is essential for hyperphosphorylation.
AB  - Rotavirus NSP5 is a nonstructural protein that localizes in viroplasms of virus
      infected cells. NSP5 interacts with NSP2 and undergoes a complex
      posttranslational hyperphosphorylation, generating species with reduced PAGE
      mobility. Here we show that NSP5 operates as an autoregulator of its own
      phosphorylation as a consequence of two distinct activities of the protein:
      substrate and activator. We developed an in vivo hyperphosphorylation assay in
      which two NSP5 mutant constructs are cotransfected. One of them, fused to an 11
      aa tag, served as substrate whereas the other was used to map NSP5 domains
      required for activation. The activation and substrate activity could be
      uncoupled, demonstrating a hyperphosphorylation process in trans between the
      activator and substratum. This process involved dimerization of the two
      components through the 18-aa C-terminal tail. Phosphorylation of Ser-67 within
      the SDSAS motif (amino acids 63-67) was required to trigger hyperphosphorylation
      by promoting the activation function. We present evidence of casein kinase 1alpha
      being the protein kinase responsible for this key step as well as for the
      consecutive ones leading to NSP5 hyperphosphorylation.

PMID- 15520390
TI  - The axonal attractant Netrin-1 is an angiogenic factor.
AB  - Blood vessels and nerves often follow parallel trajectories, suggesting that
      distal targets use common cues that induce vascularization and innervation.
      Netrins are secreted by the floor plate and attract commissural axons toward the
      midline of the neural tube. Here, we show that Netrin-1 is also a potent vascular
      mitogen. Netrin-1 stimulates proliferation, induces migration, and promotes
      adhesion of endothelial cells and vascular smooth muscle cells with a specific
      activity comparable to vascular endothelial growth factor and platelet-derived
      growth factor. Our evidence indicates that the netrin receptor, Neogenin,
      mediates netrin signaling in vascular smooth muscle cells, but suggests that an
      unidentified receptor mediates the proangiogenic effects of Netrin-1 on
      endothelial cells. Netrin-1 also stimulates angiogenesis in vivo and augments the
      response to vascular endothelial growth factor. Thus, we demonstrate that Netrin
      1 is a secreted neural guidance cue with the unique ability to attract both blood
      vessels and axons, and suggest that other cues may also function as vascular
      endothelial growth factors.

PMID- 15520391
TI  - Understanding the key factors that control the rate of beta-hairpin folding.
AB  - Both turn sequence and interstrand hydrophobic side-chain-side-chain interaction
      have been suggested to be important determinants of beta-hairpin stability.
      However, their roles in controlling the folding dynamics of beta-hairpins have
      not been clearly determined. Herein, we investigated the structural stability and
      folding kinetics of a series of tryptophan zippers by static IR and CD
      spectroscopies and the IR temperature jump method. Our results support a beta
      hairpin folding mechanism wherein the rate-limiting event corresponds to the
      formation of the turn. We find that the logarithm of the folding rate depends
      linearly on the entropic change associated with the turn formation, where faster
      folding correlates with lower entropic cost. Moreover, a stronger turn-promoting
      sequence increases the stability of a beta-hairpin primarily by increasing its
      folding rate, whereas a stronger hydrophobic cluster increases the stability of a
      beta-hairpin primarily by decreasing its unfolding rate.

PMID- 15520392
TI  - Mechanisms of ammonia activation and ammonium ion inhibition of quinoprotein
      methanol dehydrogenase: a computational approach.
AB  - The mechanism of methanol oxidation by quinoprotein methanol dehydrogenase
      (MDH.PQQ) in combination with methanol (MDH.PQQ.methanol) involves Glu-171--CO2(
      ) general base removal of the hydroxyl proton of methanol in concert with hydride
      equivalent transfer to the >C5=O quinone carbon of pyrroloquinoline quinone (PQQ)
      and rearrangement to hydroquinone (PQQH2) with release of formaldehyde. Molecular
      dynamics (MD) studies of the structures of MDH.PQQ.methanol in the presence of
      activator NH3 and inhibitor NH4(+) have been carried out. In the MD structure of
      MDH.PQQ.methanol.NH3, the hydrated NH3 resides at a distance of approximately 24
      A away from methanol and the ortho-quinone portion of PQQ. As such, influence of
      NH3 on the oxidation reaction is not probable. We find that NH4(+) competes with
      the substrate by hydrogen-bonding to Glu-171CO2(-) such that the
      MDH.PQQ.methanol.NH4(+) complex is not reactive. Ammonia readily forms imines
      with quinone. Imines are present in solution as neutral (>C5=NH) and protonated
      (>C5=NH2(+)) species. MD simulations establish that the >C5=NH2(+) derivative of
      MDH.PQQ(NH2(+).methanol structure is unreactive because of the nonproductive
      means of methanol binding. The structure obtained by the MD simulations with the
      neutral >C5=NH imine of MDH.PQQ(NH).methanol structure is similar to the reactive
      MDH.PQQ.methanol complex. This active site geometry allows for catalysis of
      hydride equivalent transfer to the >C5=NH of PQQ(NH) by concerted Glu-171CO(2)(-)
      general-base removal of the H-OCH3 proton and Arg-324H+ general-acid proton
      transfer to the imine nitrogen. Enzyme-bound <C5(H)NH2 derivative of PQQ
      [PQQ(NH)] and CH(2)O product are formed.

PMID- 15520393
TI  - Ferromagnesian postperovskite silicates in the D'' layer of the Earth.
AB  - Natural olivine with 12 mol % Fe(2)SiO(4) and synthetic orthopyroxenes with 20%
      and 40% FeSiO(3) were studied beyond the pressure-temperature conditions of the
      core-mantle boundary. All samples were found to convert entirely or partially
      into the CaIrO(3) postperovskite structure, which was recently reported for pure
      MgSiO(3). The incorporation of Fe greatly reduces the pressure needed for the
      transition and establishes the new phase as the major component of the D'' layer.
      With the liquid core as an unlimited reservoir of iron, core-mantle reactions
      could further enrich the iron content in this phase and explain the intriguing
      seismic signatures observed in the D'' layer.

PMID- 15520395
TI  - Discriminating males alter sperm production between species.
AB  - Prezygotic reproductive isolation and its importance in speciation is
      traditionally approached from the viewpoint of those events that occur before
      mating. However, recent interest in sperm competition theory has shown that
      prezygotic isolation can be affected by mechanisms that occur after mating but
      before fertilization. One neglected aspect of these studies is how the cost of
      sperm production might play a role in species isolation. We examined differential
      sperm production in a species whose males are sexually parasitized by a unisexual
      gynogenetic species. Gynogens are clonal females that require sperm from males of
      closely related bisexual species to initiate embryogenesis. We tested for
      differential sperm production by male sailfin mollies (Poecilia latipinna) when
      they were in the presence of either a heterospecific, gynogenetic female
      (Poecilia formosa, Amazon molly) or a conspecific female. We found that
      previously demonstrated male mate choice for conspecific over heterospecific
      females also is revealed in sperm production. Males from both an allopatric and a
      sympatric population produce more sperm when in the presence of a conspecific
      female than when in the presence of a heterospecific female. We suggest that
      differential sperm production also could play a role in prezygotic reproductive
      isolation in bisexual species complexes that occur in sympatry.

PMID- 15520396
TI  - An acoustic microscopy technique reveals hidden morphological defenses in
      Daphnia.
AB  - Inducible defenses are common strategies for coping with the selective force of
      predation in heterogeneous environments. In recent years the conspicuous and
      often dramatic morphological plasticity of several waterflea species of the genus
      Daphnia have been found to be inducible defenses activated by chemical cues
      released by predators. However, the exact defensive mechanisms remained
      mysterious. Because even some minute morphological alterations proved to be
      protective against predatory invertebrates, it has been suggested that the
      visible morphological changes are only the tip of the iceberg of the entire
      protective mechanisms. Here we applied a method of ultrasonic microscopy with
      vector contrast at 1.2 GHz to probe hidden morphological defenses. We found that
      induction with predator kairomones increases the stability of the carapace in two
      Daphnia species up to 350%. This morphological plasticity provides a major
      advantage for the induced morphs during predation because predatory invertebrates
      need to crush or puncture the carapace of their prey to consume them. Our
      ultrastructural analyses revealed that the internal architecture of the carapace
      ensures maximal rigidity with minimal material investment. Our results uncover
      hidden morphological plasticity and suggest a reconsideration of former
      classification systems in defended and undefended genotypes in Daphnia and
      possibly in other prey organisms as well.

PMID- 15520394
TI  - Growth factors essential for self-renewal and expansion of mouse spermatogonial
      stem cells.
AB  - Spermatogonial stem cells (SSCs) self-renew and produce large numbers of
      committed progenitors that are destined to differentiate into spermatozoa
      throughout life. However, the growth factors essential for self-renewal of SSCs
      remain unclear. In this study, a serum-free culture system and a transplantation
      assay for SSCs were used to identify exogenous soluble factors that promote
      proliferation of SSCs. Mouse pup testis cells were enriched for SSCs by selection
      with an anti-Thy-1 antibody and cultured on STO (SIM mouse embryo-derived
      thioguanine and ouabain resistant) feeders in a serum-free defined medium. In the
      presence of glial cell line-derived neurotrophic factor (GDNF), SSCs from DBA/2J
      strain mice formed densely packed clumps of cells and continuously proliferated.
      However, other strains of mice required the addition of soluble GDNF-family
      receptor alpha-1 and basic fibroblast growth factor to support replication. The
      functional transplantation assay proved that the clump-forming cells are indeed
      SSCs. Thus, GDNF-induced cell signaling plays a central role in SSC self-renewal.
      The number of SSCs in culture doubled every 5.6 days, and the clump-forming cells
      strongly expressed Oct-4. Under these conditions, SSCs proliferated over 6
      months, reconstituted long-term spermatogenesis after transplantation into
      recipient testes, and restored fertility to infertile recipients. The
      identification of exogenous factors that allow continuous proliferation of SSCs
      in vitro establishes the foundation to study the basic biology of SSCs and makes
      possible germ-line modification by sophisticated technologies. Moreover, the
      ability to recover, culture indefinitely, and transplant SSCs will make the germ
      line of individual males available for periods extending beyond a normal
      lifetime.

PMID- 15520398
TI  - Relation of type 2 diabetes to individual admixture and candidate gene
      polymorphisms in the Hispanic American population of San Luis Valley, Colorado.

PMID- 15520397
TI  - In vivo dynamics of chromatin-associated complex formation in mammalian
      nucleotide excision repair.
AB  - Chromatin is the substrate for many processes in the cell nucleus, including
      transcription, replication, and various DNA repair systems, all of which require
      the formation of multiprotein machineries on the chromatin fiber. We have
      analyzed the kinetics of in vivo assembly of the protein complex that is
      responsible for nucleotide excision repair (NER) in mammalian cells. Assembly is
      initiated by UV irradiation of a small area of the cell nucleus, after which the
      accumulation of GFP-tagged NER proteins in the DNA-damaged area is measured,
      reflecting the establishment of the dual-incision complex. The dynamic behavior
      of two NER proteins, ERCC1-XPF and TFIIH, was studied in detail. Results show
      that the repair complex is assembled with a rate of approximately 30 complexes
      per second and is not diffusion limited. Furthermore, we provide in vivo evidence
      that not only binding of TFIIH, but also its helicase activity, is required for
      the recruitment of ERCC1-XPF. These studies give quantitative insight into the de
      novo assembly of a chromatin-associated protein complex in living cells.

PMID- 15520399
TI  - PTPN11 mutations in patients with LEOPARD syndrome: a French multicentric
      experience.

PMID- 15520400
TI  - Rapid detection of CFTR gene rearrangements impacts on genetic counselling in
      cystic fibrosis.

PMID- 15520401
TI  - No live individual homozygous for a novel endoglin mutation was found in a
      consanguineous Arab family with hereditary haemorrhagic telangiectasia.

PMID- 15520402
TI  - Germline CHEK2*1100delC mutations in breast cancer patients with multiple primary
      cancers.

PMID- 15520403
TI  - Clinical genetic counselling for familial cancers requires reliable data on
      familial cancer risks and general action plans.
AB  - Familial cancer clustering, without obvious heritability, poses a major challenge
      for current cancer risk assessment and management. Reliable determination of
      familial risks for cancer is important for clinical genetic counselling, but
      medically verified data on familial risks for many malignancies have been
      limited. However, the nationwide Swedish Family-Cancer Database allows a reliable
      characterisation of familial risk for all major neoplasms. Even though alert
      genetic counsellors and certainly clinical cancer geneticists will consider
      familial cancer clustering in their purview, the standard medical referral
      systems, which have already been shown to be poor in capturing and referring
      families at high risk for heritable cancers, are unlikely to ascertain familial
      aggregations of other cancers that are not known to belong to an inherited cancer
      syndrome. The data will be helpful in implementing evidence based guidelines for
      helping the general medical system to ascertain and refer even familial cancer
      clusters to cancer genetics professionals.

PMID- 15520405
TI  - Retraction statement.

PMID- 15520406
TI  - Sequence family variant loss from the AZFc interval of the human Y chromosome,
      but not gene copy loss, is strongly associated with male infertility.
AB  - BACKGROUND: Complete deletion of the complete AZFc interval of the Y chromosome
      is the most common known genetic cause of human male infertility. Two partial
      AZFc deletions (gr/gr and b1/b3) that remove some copies of all AZFc genes have
      recently been identified in infertile and fertile populations, and an association
      study indicates that the resulting gene dose reduction represents a risk factor
      for spermatogenic failure. METHODS: To determine the incidence of various partial
      AZFc deletions and their effect on fertility, we combined quantitative and
      qualitative analyses of the AZFc interval at the DAZ and CDY1 loci in 300
      infertile men and 399 control men. RESULTS: We detected 34 partial AZFc deletions
      (32 gr/gr deletions), arising from at least 19 independent deletion events, and
      found gr/gr deletion in 6% of infertile and 3.5% of control men (p>0.05). Our
      data provide evidence for two large AZFc inversion polymorphisms, and for
      relative hot and cold spots of unequal crossing over within the blocks of
      homology that mediate gr/gr deletion. Using SFVs (sequence family variants), we
      discriminate DAZ1/2, DAZ3/4, CDY1a (proximal), and CDY1b (distal) and define four
      types of DAZ-CDY1 gr/gr deletion. CONCLUSIONS: The only deletion type to show an
      association with infertility was DAZ3/4-CDY1a (p = 0.042), suggesting that most
      gr/gr deletions are neutral variants. We see a stronger association, however,
      between loss of the CDY1a SFV and infertility (p = 0.002). Thus, loss of this SFV
      through deletion or gene conversion could be a major risk factor for male
      infertility.

PMID- 15520404
TI  - TLR4 and TNF-alpha polymorphisms are associated with an increased risk for severe
      sepsis following burn injury.
AB  - CONTEXT: Sepsis, organ failure, and shock remain common among patients with
      moderate to severe burn injuries. The inability of clinical factors to identify
      at-risk patients suggests that genetic variation may influence the risk for
      serious infection and the outcome from severe injury. OBJECTIVE: Resolution of
      genetic variants associated with severe sepsis following burn injury. PATIENTS: A
      total of 159 patients with burns > or =20% of their total body surface area or
      any smoke inhalation injury without significant non-burn related trauma (injury
      severity score (ISS)> or =16), traumatic or anoxic brain injury, or spinal cord
      injury and who survived more than 48 h post-admission. METHODS: Candidate single
      nucleotide polymorphisms (SNPs) within bacterial recognition (TLR4 +896, CD14 
      159) and inflammatory response (TNF-alpha -308, IL-1beta -31, IL-6 -174) loci
      were evaluated for association with increased risk for severe sepsis (sepsis plus
      organ dysfunction or septic shock) and mortality. RESULTS: After adjustment for
      age, full-thickness burn size, ethnicity, and gender, carriage of the TLR4 +896 G
      allele imparted at least a 1.8-fold increased risk of developing severe sepsis
      following a burn injury, relative to AA homozygotes (adjusted odds ratio (aOR)
      6.4; 95% confidence interval (CI) 1.8 to 23.2). Carriage of the TNF-alpha -308 A
      allele imparted a similarly increased risk, relative to GG homozygotes (aOR =
      4.5; 95% CI 1.7 to 12.0). None of the SNPs examined were significantly associated
      with mortality. CONCLUSIONS: The TLR4 +896 and TNF-alpha -308 polymorphisms were
      significantly associated with an increased risk for severe sepsis following burn
      trauma.

PMID- 15520407
TI  - FRG2, an FSHD candidate gene, is transcriptionally upregulated in differentiating
      primary myoblast cultures of FSHD patients.
AB  - BACKGROUND: Autosomal dominant facioscapulohumeral muscular dystrophy (FSHD) is
      associated with partial deletion of the subtelomeric D4Z4 repeat array on
      chromosome 4qter. This chromosomal rearrangement may result in regional chromatin
      relaxation and transcriptional deregulation of genes nearby. METHODS AND RESULTS:
      Here we describe the isolation and characterisation of FRG2, a member of a
      chromosomally dispersed gene family, mapping only 37 kb proximal to the D4Z4
      repeat array. Homology and motif searches yielded no clues to the function of the
      predicted protein. FRG2 expression is undetectable in all tissues tested except
      for differentiating myoblasts of FSHD patients, which display low, yet distinct
      levels of FRG2 expression, partly from chromosome 4 but predominantly originating
      from its homologue on chromosome 10. However, in non-FSHD myopathy patients only
      distantly related FRG2 homologues are transcribed, while differentiating
      myoblasts from healthy controls fail to express any member of this gene family.
      Moreover, fibroblasts of FSHD patients and control individuals undergoing forced
      Ad5-MyoD mediated myogenesis show expression of FRG2 mainly originating from
      chromosome 10. Luciferase reporter assays show that the FRG2 promoter region can
      direct high levels of expression but is inhibited by increasing numbers of D4Z4
      repeat units. Transient transfection experiments with FRG2 fusion-protein
      constructs reveal nuclear localisation and apparently FRG2 overexpression causes
      a wide range of morphological changes. CONCLUSION: The localisation of FRG2 genes
      close to the D4Z4 repeats on chromosome 4 and 10, their transcriptional
      upregulation specifically in FSHD myoblast cultures, potential involvement in
      myogenesis, and promoter properties qualify FRG2 as an attractive candidate for
      FSHD pathogenesis.

PMID- 15520408
TI  - Neurofibromatous neuropathy in neurofibromatosis 1 (NF1).
AB  - BACKGROUND: Neurofibromatosis 1 (NF1) is a common, autosomal dominant,
      neurocutaneous disease that is clinically and genetically distinct from the rare
      condition neurofibromatosis 2 (NF2). Neurofibromatous neuropathy has been
      regarded as a common feature of NF2, but is an unusual and unexplained
      complication of NF1. The clinical and histological features of the NF1 neuropathy
      are distinct from those encountered in NF2. We describe eight patients with a
      symmetrical polyneuropathy, which has been called neurofibromatous neuropathy.
      METHODS: Clinical assessments, laboratory investigations, neuroimaging, and
      neurophysiology were undertaken in eight individuals with neurofibromatous
      neuropathy. None were referred because of neuropathic symptoms. Two subjects
      underwent sural nerve biopsy and three agreed to mutational analysis. RESULTS:
      The patients had an indolent symmetrical predominantly sensory axonal neuropathy
      and unusually early development of large numbers of neurofibromas. The biopsied
      nerves showed diffuse neurofibromatous change and disruption of the perineurium.
      Two patients developed a high grade malignant peripheral nerve sheath tumour.
      Disease causing mutations were detected in two individuals and molecular studies
      did not reveal any whole gene deletions. CONCLUSIONS: Neurofibromatous neuropathy
      occurred in 1.3% of 600 patients with NF1. Its cause may be a diffuse neuropathic
      process arising from inappropriate signalling between Schwann cells, fibroblasts,
      and perineurial cells.

PMID- 15520409
TI  - Missense mutations of ACTA1 cause dominant congenital myopathy with cores.

PMID- 15520410
TI  - A novel locus for autosomal recessive form of hypotrichosis maps to chromosome
      3q26.33-q27.3.

PMID- 15520411
TI  - Putative functional alleles of DYX1C1 are not associated with dyslexia
      susceptibility in a large sample of sibling pairs from the UK.

PMID- 15520412
TI  - A new locus for a childhood onset, slowly progressive autosomal recessive
      spinocerebellar ataxia maps to chromosome 11p15.

PMID- 15520413
TI  - The ser9gly SNP in the dopamine D3 receptor causes a shift from cAMP related to
      PGE2 related signal transduction mechanisms in transfected CHO cells.

PMID- 15520414
TI  - A gene responsible for autosomal dominant auditory neuropathy (AUNA1) maps to
      13q14-21.

PMID- 15520415
TI  - Increased recurrence risk in congenital disorders of glycosylation type Ia (CDG
      Ia) due to a transmission ratio distortion.

PMID- 15520416
TI  - Summaries for patients. Cost-effectiveness of rate control vs. rhythm control for
      patients with atrial fibrillation.

PMID- 15520417
TI  - Summaries for patients. Description of the 2003 severe acute respiratory syndrome
      outbreak in Hong Kong.

PMID- 15520418
TI  - Summaries for patients. Diagnosis of renal artery stenosis.

PMID- 15520419
TI  - Summaries for patients. Using a video to teach patients about colorectal cancer
      screening.

PMID- 15520420
TI  - To butterfly or to needle: the specimen testing question.

PMID- 15520421
TI  - Cost-effectiveness of rhythm versus rate control in atrial fibrillation.
AB  - BACKGROUND: Atrial fibrillation is the most common type of sustained cardiac
      arrhythmia, but recent trials have identified no clear advantage of rhythm
      control over rate control. Consequently, economic factors often play a role in
      guiding treatment selection. OBJECTIVE: To estimate the cost-effectiveness of
      rhythm-control versus rate-control strategies for atrial fibrillation in the
      Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM).
      DESIGN: Retrospective economic evaluation. Nonparametric bootstrapping was used
      to estimate the distribution of incremental costs and effects on the cost
      effectiveness plane. DATA SOURCES: Data on survival and use of health care
      resources were obtained for all 4060 AFFIRM participants. Unit costs were
      estimated from various U.S. databases. TARGET POPULATION: Patients with atrial
      fibrillation who were 65 years of age or who had other risk factors for stroke or
      death, similar to those enrolled in AFFIRM. TIME HORIZON: Mean follow-up of 3.5
      years. PERSPECTIVE: Third-party payer. INTERVENTIONS: Management of patients with
      atrial fibrillation with antiarrhythmic drugs (rhythm control) compared with
      drugs that control heart rate (rate control). OUTCOME MEASURES: Mean survival,
      resource use, costs, and cost-effectiveness. RESULTS OF BASE-CASE ANALYSIS: A
      mean survival gain of 0.08 year (P = 0.10) was observed for rate control.
      Patients in the rate-control group used fewer resources (hospital days, pacemaker
      procedures, cardioversions, and short-stay and emergency department visits). Rate
      control costs 5077 dollars less per person than rhythm control. RESULTS OF
      SENSITIVITY ANALYSIS: Cost savings ranged from 2189 dollars o 5481 dollars per
      person. Rhythm control was more costly and less effective than rate control in
      95% of the bootstrap replicates over a wide range of cost assumptions.
      LIMITATIONS: Resource use was limited to key items collected in AFFIRM, and the
      results are generalizable only to similar patient populations with atrial
      fibrillation. CONCLUSION: Rate control is a cost-effective approach to the
      management of atrial fibrillation compared with maintenance of sinus rhythm in
      patients with atrial fibrillation similar to those enrolled in AFFIRM.

PMID- 15520422
TI  - The epidemiology of severe acute respiratory syndrome in the 2003 Hong Kong
      epidemic: an analysis of all 1755 patients.
AB  - BACKGROUND: As yet, no one has written a comprehensive epidemiologic account of a
      severe acute respiratory syndrome (SARS) outbreak from an affected country.
      OBJECTIVE: To provide a comprehensive epidemiologic account of a SARS outbreak
      from an affected territory. DESIGN: Epidemiologic analysis. SETTING: The 2003
      Hong Kong SARS outbreak. PARTICIPANTS: All 1755 cases and 302 deaths.
      MEASUREMENTS: Sociodemographic characteristics; infection clusters by time,
      occupation, setting, and workplace; and geospatial relationships were determined.
      The mean and variance in the time from infection to onset (incubation period)
      were estimated in a small group of patients with known exposure. The mean and
      variance in time from onset to admission, from admission to discharge, or from
      admission to death were calculated. Logistic regression was used to identify
      important predictors of case fatality. RESULTS: 49.3% of patients were infected
      in clinics, hospitals, or elderly or nursing homes, and the Amoy Gardens cluster
      accounted for 18.8% of cases. The ratio of women to men among infected
      individuals was 5:4. Health care workers accounted for 23.1% of all reported
      cases. The estimated mean incubation period was 4.6 days (95% CI, 3.8 to 5.8
      days). Mean time from symptom onset to hospitalization varied between 2 and 8
      days, decreasing over the course of the epidemic. Mean time from onset to death
      was 23.7 days (CI, 22.0 to 25.3 days), and mean time from onset to discharge was
      26.5 days (CI, 25.8 to 27.2 days). Increasing age, male sex, atypical presenting
      symptoms, presence of comorbid conditions, and high lactate dehydrogenase level
      on admission were associated with a greater risk for death. LIMITATIONS:
      Estimates of the incubation period relied on statistical assumptions because few
      patients had known exposure times. Temporal changes in case management as the
      epidemic progressed, unavailable treatment information, and several potentially
      important factors that could not be thoroughly analyzed because of the limited
      sample size complicate interpretation of factors related to case fatality.
      CONCLUSIONS: This analysis of the complete data on the 2003 SARS epidemic in Hong
      Kong has revealed key epidemiologic features of the epidemic as it evolved.

PMID- 15520423
TI  - Accuracy of computed tomographic angiography and magnetic resonance angiography
      for diagnosing renal artery stenosis.
AB  - BACKGROUND: Timely, accurate detection of renal artery stenosis is important
      because this disorder may be a potentially curable cause of hypertension and
      renal impairment. OBJECTIVE: To determine the validity of computed tomographic
      angiography (CTA) and magnetic resonance angiography (MRA) compared with digital
      subtraction angiography (DSA) for detection of renal artery stenosis. DESIGN:
      Prospective multicenter comparative study conducted from 1998 to 2001. Two panels
      of 3 observers judged CTA and MRA image data and were blinded to all other
      results. Digital subtraction angiography images were evaluated by consensus.
      SETTING: 3 large teaching hospitals and 3 university hospitals in the
      Netherlands. PATIENTS: 402 hypertensive patients with suspected renal artery
      stenosis were included. A group of 356 patients who underwent all 3 diagnostic
      tests was used for analysis. MEASUREMENTS: Reproducibility was assessed by
      calculating interobserver agreement. Diagnostic performance was evaluated in
      terms of sensitivity, specificity, and other diagnostic variables.
      Atherosclerotic stenoses of 50% or greater and fibromuscular dysplasia were
      considered clinically relevant. RESULTS: Twenty percent of patients who underwent
      all 3 tests had clinically relevant renal artery stenosis. Moderate interobserver
      agreement was found, with kappa values ranging from 0.59 to 0.64 for CTA and 0.40
      to 0.51 for MRA. The combined sensitivity and specificity were 64% (95% CI, 55%
      to 73%) and 92% (CI, 90% to 95%) for CTA and 62% (CI, 54% to 71%) and 84% (CI,
      81% to 87%) for MRA. LIMITATIONS: Eighteen percent of the patients were included
      nonconsecutively. Digital subtraction angiography may be an imperfect reference
      test. CONCLUSION: Computed tomographic angiography and MRA are not reproducible
      or sensitive enough to rule out renal artery stenosis in hypertensive patients.
      Therefore, DSA remains the diagnostic method of choice. *For a list of the other
      investigators and research coordinators who participated in RADISH, see the
      Appendix.

PMID- 15520425
TI  - Patient education for colon cancer screening: a randomized trial of a video
      mailed before a physical examination.
AB  - BACKGROUND: Colorectal cancer screening is underused, and primary care clinicians
      are challenged to provide patient education within the constraints of busy
      practices. OBJECTIVE: To test the effect of an educational video, mailed to
      patients' homes before a physical examination, on performance of colorectal
      cancer screening, particularly sigmoidoscopy. DESIGN: Randomized, controlled
      trial. SETTING: 5 primary care practices in central Massachusetts. PARTICIPANTS:
      938 patients age 50 to 74 years who were scheduled for an upcoming physical
      examination, had no personal history of colorectal cancer, and were eligible for
      lower-endoscopy screening according to current guidelines. INTERVENTION:
      Participants were randomly assigned to receive usual care (n = 488) or a video
      about colorectal cancer, the importance of early detection, and screening options
      (n = 450). MEASUREMENTS: Baseline and 6-month follow-up telephone assessments
      were conducted. A dependent variable classified screening since baseline as 1)
      sigmoidoscopy with or without other tests, 2) another test or test combination,
      or 3) no tests. RESULTS: Overall screening rates were the same in the
      intervention and control groups (55%). In regression modeling, intervention
      participants were nonsignificantly more likely to complete sigmoidoscopy alone or
      in combination with another test (odds ratio, 1.22 [95% CI, 0.88 to 1.70]).
      Intervention dose (viewing at least half of the video) was significantly related
      to receiving sigmoidoscopy with or without another test (odds ratio, 2.81 [CI,
      1.85 to 4.26]). Recruitment records showed that at least 23% of people coming for
      periodic health assessments were currently screened by a lower-endoscopy
      procedure and therefore were not eligible. LIMITATIONS: The primary care sample
      studied consisted primarily of middle-class white persons who had high screening
      rates at baseline. The results may not be generalizable to other populations. The
      trial was conducted during a period of increased health insurance coverage for
      lower-endoscopy procedures and public media attention to colon cancer screening.
      CONCLUSIONS: A mailed video had no effect on the overall rate of colorectal
      cancer screening and only modestly improved sigmoidoscopy screening rates among
      patients in primary care practices.

PMID- 15520426
TI  - Meta-analysis: angiotensin-receptor blockers in chronic heart failure and high
      risk acute myocardial infarction.
AB  - BACKGROUND: The role of angiotensin-receptor blockers (ARBs) in treating patients
      with chronic heart failure and high-risk acute myocardial infarction (MI) has
      been controversial, and recent clinical trials provide more information on this
      topic. PURPOSE: To quantify the effect of ARBs when compared with placebo (with
      and without background angiotensin-converting enzyme [ACE] inhibitors) and ACE
      inhibitors on all-cause mortality and heart failure hospitalizations in patients
      with chronic heart failure and high-risk acute MI. DATA SOURCES: Data from
      original research published through 13 November 2003. STUDY SELECTION: Predefined
      criteria were used to identify 24 trials. DATA EXTRACTION: 2 reviewers
      independently collected information on study characteristics and data on all
      cause mortality and heart failure hospitalization. DATA SYNTHESIS: 24 trials
      involving 38 080 patients were included. Analysis of chronic heart failure trials
      revealed that 1) ARBs were associated with reduced all-cause mortality (odds
      ratio [OR], 0.83 [95% CI, 0.69 to 1.00]) and heart failure hospitalizations (OR,
      0.64 [CI, 0.53 to 0.78]) as compared with placebo; 2) for ARBs versus ACE
      inhibitors, all-cause mortality (OR, 1.06 [CI, 0.90 to 1.26]) and heart failure
      hospitalization (OR, 0.95 [CI, 0.80 to 1.13]) did not differ; 3) and for
      combinations of ARBs plus ACE inhibitors versus ACE inhibitors alone, all-cause
      mortality was not reduced (OR, 0.97 [CI, 0.87 to 1.08]) but heart failure
      hospitalizations were reduced (OR, 0.77 [CI, 0.69 to 0.87]). For patients with
      high-risk acute MI, 2 randomized trials compared ARBs with ACE inhibitors but did
      not reveal differences in all-cause mortality or heart failure hospitalization.
      LIMITATIONS: Comparative economic data between ARBs and ACE inhibitors are
      lacking. CONCLUSIONS: Because ACE inhibitors and ARBs do not differ in efficacy
      for reducing all-cause mortality and heart failure hospitalizations in patients
      with chronic heart failure and in patients with high-risk acute MI, ARBs should
      be regarded as suitable alternatives to ACE inhibitors.

PMID- 15520427
TI  - Weighing the evidence for expanding physician supply.
AB  - For 2 decades, health planners have forecasted impending physician surpluses, and
      policy decisions related to medical schools and residency programs have been
      based on such expectations. However, these much-heralded surpluses never
      materialized, and a growing body of data and opinion now point in the other
      direction. The question at the forefront is whether the United States is instead
      headed for a physician shortage. What is the evidence? This paper reviews the
      trends that link economic growth to health care spending and to the demand for
      physicians. It assesses the current environment by examining trends in the
      characteristics of clinical practice, signals from the medical market, and recent
      experiences of physician shortages in other English-speaking countries; it also
      discusses why past forecasting approaches may have failed. Taken together, this
      body of information indicates that physician shortages are emerging and that they
      will probably worsen over the next 2 decades. By 2020 or 2025, the deficit could
      be as great as 200,000 physicians--20% of the needed workforce. If remedies are
      to be found, the nature of the problem must be appreciated, and a consensus to
      solve it must be reached.

PMID- 15520428
TI  - Testing for hepatitis C virus infection should be routine for persons at
      increased risk for infection.
AB  - In the United States, chronic hepatitis C virus (HCV) infection affects an
      estimated 3 million persons, most younger than 50 years of age. It is one of the
      leading causes of chronic liver disease morbidity and mortality and the most
      common indication for liver transplantation. Effective treatment can eradicate
      the virus and eliminate or reduce liver inflammation and fibrosis, and counseling
      and immunization can modify or prevent the adverse effect of cofactors (for
      example, alcohol consumption or co-infections) on disease progression. However,
      controversy surrounds the need to routinely identify asymptomatic HCV-infected
      persons. Because no data currently demonstrate that treatment or other
      interventions will reduce future cases of HCV-related chronic disease and deaths,
      the U.S. Preventive Services Task Force found insufficient evidence to recommend
      for or against routine screening for HCV infection in adults at high risk.
      Chronic hepatitis C would require many years of follow-up to determine the
      incidence of complication after treatment of or other interventions in
      asymptomatic persons. It seems inappropriate to wait several decades to measure
      the impact of early identification of this viral infection when current data
      support a positive therapeutic effect that points to long-term benefits. In
      addition, treatment and other interventions must be provided before cirrhosis or
      liver failure occurs. Therefore, medical and public health professionals should
      continue the practice of screening persons for risk factors; offering testing to
      those at increased risk for HCV infection; and providing infected persons with
      appropriate counseling, medical evaluation, and treatment.

PMID- 15520429
TI  - The meaning of the U.S. Preventive Services Task Force grade I recommendation:
      screening for hepatitis C virus infection.
AB  - The U.S. Preventive Services Task Force (USPSTF) formulates evidence-based
      recommendations for clinical preventive services. These recommendations are
      communicated by letter grades that reflect the quality of evidence and the
      magnitude of net health benefit expected from delivering the preventive service.
      When the USPSTF finds insufficient evidence to determine the balance of health
      benefits or harms of delivering a preventive service, because of a lack of
      studies, poor-quality studies, or good-quality studies with conflicting results,
      the USPSTF assigns the service an I letter grade. The USPSTF found insufficient
      evidence to recommend for or against screening for hepatitis C virus infection in
      high-risk individuals (I letter grade). This recommendation reflects the need for
      further research that would provide adequate evidence to assess the net health
      benefit for persons screened for hepatitis C virus infection.

PMID- 15520430
TI  - Is there a role for maintaining sinus rhythm in patients with atrial
      fibrillation?
AB  - Recent studies have indicated that outcomes in patients with atrial fibrillation
      who are managed with rate control and anticoagulation are similar to those in
      patients who have maintenance of sinus rhythm. These studies did not include
      important groups of patients with atrial fibrillation in whom antiarrhythmic
      therapy may be appropriate. This perspective argues for the maintenance of sinus
      rhythm and for the use of antiarrhythmic therapy that includes medications,
      invasive procedures, and a combination of both in appropriate patients.

PMID- 15520431
TI  - To be or not to be in normal sinus rhythm: what do we really know?

PMID- 15520432
TI  - Pitfalls in imaging for renal artery stenosis.

PMID- 15520433
TI  - The U.S. physician workforce: serious questions raised, answers needed.

PMID- 15520434
TI  - Professionalism and the medical student.

PMID- 15520436
TI  - A lesson from the third year.

PMID- 15520437
TI  - Low-carbohydrate diets.

PMID- 15520438
TI  - Rosiglitazone for treatment of HIV lipodystrophy.

PMID- 15520439
TI  - Residents' work hours.

PMID- 15520440
TI  - Residents' work hours.

PMID- 15520441
TI  - Residents' work hours.

PMID- 15520442
TI  - Residents' work hours.

PMID- 15520443
TI  - Residents' work hours.

PMID- 15520444
TI  - Corticosteroids for septic shock.

PMID- 15520445
TI  - Tadalafil in primary pulmonary arterial hypertension.

PMID- 15520446
TI  - On the hepatic mechanism of HDL assembly by the ABCA1/apoA-I pathway.
AB  - The mechanism for the assembly of HDL with cellular lipid by ABCA1 and helical
      apolipoprotein was investigated in hepatocytes. Both HepG2 cells and mouse
      primary culture hepatocytes produced HDL with apolipoprotein A-I (apoA-I) whether
      endogenously synthesized or exogenously provided. Probucol, an ABCA1 inactivator,
      inhibited these reactions, as well as the reversible binding of apoA-I to HepG2.
      Primary cultured hepatocytes of ABCA1-deficient mice also lacked HDL production
      regardless of the presence of exogenous apoA-I. HepG2 cells secreted apoA-I into
      the medium even when ABCA1 was inactivated by probucol, but it was all in a free
      form as HDL production was inhibited. When a lipid-free apoA-I-specific
      monoclonal antibody, 725-1E2, was present in the culture medium, production of
      HDL was suppressed, whether with endogenous or exogenously added apoA-I, and the
      antibody did not influence HDL already produced by HepG2 cells. We conclude that
      the main mechanism for HDL assembly by endogenous apoA-I in HepG2 cells is an
      autocrine-like reaction in which apoA-I is secreted and then interacts with
      cellular ABCA1 to generate HDL.

PMID- 15520448
TI  - Relation of the size and intracellular sorting of apoB to the formation of VLDL 1
      and VLDL 2.
AB  - In this study, we tested the hypothesis that two separate pathways, the two-step
      process and an apolipoprotein B (apoB) size-dependent lipidation process, give
      rise to different lipoproteins. Expression of apoB-100 and C-terminally truncated
      forms of apoB-100 in McA-RH7777 cells demonstrated that VLDL particles can be
      assembled by apoB size-dependent linear lipidation, resulting in particles whose
      density is inversely related to the size of apoB. This lipidation results in a
      LDL-VLDL 2 particle containing apoB-100. VLDL 1 is assembled by the two-step
      process by apoB-48 and larger forms of apoB but not to any significant amount by
      apoB-41. The major amount of intracellular apoB-80 and apoB-100 banded with a
      mean density of 1.10 g/ml. Its formation was dependent on the sequence between
      apoB-72 and apoB-90. This dense particle, which is retained in the cell, possibly
      by chaperones or association with the microsomal membrane, is a precursor of
      secreted VLDL 1. The intracellular LDL-VLDL 2 particles formed during size
      dependent lipidation appear to be the precursors of intracellular VLDL 1. We
      propose that the dense apoB-100 intracellular particle is converted to LDL-VLDL 2
      by size-dependent lipidation. LDL-VLDL 2 is secreted or converted to VLDL 1 by
      the uptake of the major amount of triglycerides.

PMID- 15520447
TI  - Thioredoxin-interacting protein deficiency disrupts the fasting-feeding metabolic
      transition.
AB  - Through a positional cloning approach, the thioredoxin-interacting protein gene
      (Txnip) was recently identified as causal for a form of combined hyperlipidemia
      in mice (Bodnar, J. S., A. Chatterjee, L. W. Castellani, D. A. Ross, J. Ohmen, J.
      Cavalcoli, C. Wu, K. M. Dains, J. Catanese, M. Chu, S. S. Sheth, K. Charugundla,
      P. Demant, D. B. West, P. de Jong, and A. J. Lusis. 2002. Positional cloning of
      the combined hyperlipidemia gene Hyplip1. Nat. Genet. 30: 110-116). We now show
      that Txnip-deficient mice in the fed state exhibit a metabolic profile similar to
      fasted mice, including increased levels of plasma ketone bodies and free fatty
      acids, decreased glucose, and increased hepatic expression of peroxisome
      proliferator-activated receptor-gamma coactivator-1alpha, phosphoenolpyruvate
      carboxykinase, glucose-6-phosphatase, and acyl-CoA oxidase. Dramatic differences
      in the expression of key metabolic enzymes were also observed in other tissues,
      and the fat-to-muscle ratio of Txnip-deficient mice was increased by
      approximately 40%. We demonstrate an effect of Txnip on the redox status, as the
      Txnip-deficient mice in the fed state had a significant increase in the ratio of
      NADH to NAD(+). Surprisingly, we observed that Txnip-deficient mice and wild-type
      mice had similar levels of thioredoxin activity, suggesting that the effects of
      Txnip deficiency may be mediated in part by other interactions. These results
      indicate a role for Txnip in the metabolic response to feeding and the
      maintenance of the redox status.

PMID- 15520449
TI  - Potential role of ABCA7 in cellular lipid efflux to apoA-I.
AB  - ABCA7 is homologous to ABCA1 and has recently been shown in cell culture to bind
      apolipoprotein A-I (apoA-I) and to promote the efflux of phospholipids. However,
      it is not known if ABCA7 promotes lipid efflux in vivo. When expressed in HEK293
      cells, both human and mouse ABCA7 promoted phospholipid efflux to apoA-I but no
      detectable cholesterol efflux. However, genetic knockdown of ABCA7 in mouse
      peritoneal macrophages did not affect phospholipid or cholesterol efflux to apoA
      I. Moreover, in ABCA1-knockout macrophages, there was no detectable apoA-I
      stimulated phospholipid efflux, inconsistent with a residual role of ABCA7. In
      contrast to plasma membrane localization of ABCA7 in transfected embryonic kidney
      cells, immunofluorescence microscopy of endogenous ABCA7 in macrophages showed a
      predominantly intracellular localization of the protein. Strikingly,
      immunofluorescence studies of adult mouse kidney revealed an apical brush border
      membrane localization of ABCA7 in the proximal tubule, suggesting that ABCA7 may
      come in contact with apoA-I in the glomerular filtrate. Although ABCA7 does not
      contribute to apolipoprotein-mediated lipid efflux in resting macrophages, its
      cell surface location in the kidney suggests that it could serve such a role in
      tissue microenvironments.

PMID- 15520450
TI  - Role of CYP27A in cholesterol and bile acid metabolism.
AB  - The CYP27A gene encodes a mitochondrial cytochrome P450 enzyme, sterol 27
      hydroxylase, that is expressed in many different tissues and plays an important
      role in cholesterol and bile acid metabolism. In humans, CYP27A deficiency leads
      to cerebrotendinous xanthomatosis. To gain insight into the roles of CYP27A in
      the regulation of cholesterol and bile acid metabolism, cyp27A gene knockout
      heterozygous, homozygous, and wild-type littermate mice were studied. In contrast
      to homozygotes, heterozygotes had increased body weight and were mildly
      hypercholesterolemic, with increased numbers of lipoprotein particles in the low
      density lipoprotein size range. Cyp7A expression was not increased in
      heterozygotes but was in homozygotes, suggesting that parts of the homozygous
      phenotype are secondary to increased cyp7A expression and activity. Homozygotes
      exhibited pronounced hepatomegaly and dysregulation in hepatic cholesterol, bile
      acid, and fatty acid metabolism. Hepatic cholesterol synthesis and synthesis of
      bile acid intermediates were increased; however, side chain cleavage was
      impaired, leading to decreased bile salt concentrations in gallbladder bile.
      Expression of Na-taurocholate cotransporting polypeptide, the major sinusoidal
      bile salt transporter, was increased, and that of bile salt export pump, the
      major canalicular bile salt transporter, was decreased. Gender played a modifying
      role in the homozygous response to cyp27A deficiency, with females being
      generally more severely affected. Thus, both cyp27A genotype and gender affected
      the regulation of hepatic bile acid, cholesterol, and fatty acid metabolism.

PMID- 15520451
TI  - Common sequence variations in ABCG8 are related to plant sterol metabolism in
      healthy volunteers.
AB  - Polymorphisms in the ATP binding cassette (ABC) transporters ABCG5 and ABCG8 are
      related to plasma plant sterol concentrations. It is not known whether these
      polymorphisms are also associated with variations in serum plant sterol
      concentrations during interventions affecting plant sterol metabolism. We
      therefore decided to study changes in serum plant sterol concentrations with
      ABCG5/G8 polymorphisms after consumption of plant stanol esters, which decrease
      plasma plant sterol concentrations. Cholesterol-standardized serum campesterol
      and sitosterol concentrations were significantly associated with the ABCG8 T400K
      genotype, as were changes in serum plant sterol concentrations after consumption
      of plant stanols. The reduction of -57.1 +/- 38.3 10(2) x micromol/mmol
      cholesterol for sitosterol in TT subjects was significantly greater compared with
      the -36.0 +/- 18.7 reduction in subjects with the TK genotype (P = 0.021) and the
      -16.9 +/- 13.0 reduction in subjects with the KK genotype (P = 0.047). Changes in
      serum campesterol concentrations showed a comparable association. No association
      with serum LDL cholesterol was found. Genetic variation in ABCG8 not only
      explains cross-sectional differences in serum plant sterol concentrations but
      also determines a subject's responsiveness to changes in serum plant sterols
      during interventions known to affect plant sterol metabolism.

PMID- 15520452
TI  - Interaction of cholesterol with sphingosine: physicochemical characterization and
      impact on intestinal absorption.
AB  - Molecular associations between sphingomyelin and cholesterol provide a molecular
      basis for the colocalization of these lipids in plasma membrane microdomains
      (lipid rafts) and for the inhibitory effect of sphingomyelin on the intestinal
      absorption of cholesterol. Using surface pressure measurements at the air-water
      interface, we showed that sphingosine, the common sphingoid backbone of most
      sphingolipids, formed condensed lipid complexes with cholesterol. Structure
      activity relationship studies with long-chain analogs of sphingosine, together
      with molecular mechanics simulations, were consistent with a specific interaction
      between sphingosine and the alpha face of cholesterol. The uptake of micellar
      cholesterol and the effect of sphingosine on cholesterol absorption were studied
      with two human model intestinal epithelial cell lines, Caco-2 and HT-29-D4. Real
      time PCR quantifications of the putative cholesterol transporter Niemann-Pick C1
      like 1 (NPC1L1) mRNA revealed that, in these cell lines, the activity of
      cholesterol transport correlated with the level of NPC1L1 expression. In both
      cell lines, sphingosine induced a dose-dependent decrease of cholesterol
      absorption. Yet the effect of sphingosine was more dramatic in Caco-2 cells,
      which also displayed the highest expression of NPC1L1 mRNA. Altogether, these
      data suggested that sphingosine interacts specifically with cholesterol and
      inhibits the intestinal NPC1L1-dependent transport of micellar cholesterol.

PMID- 15520454
TI  - In memoriam: David L. Williams 1946-2004.

PMID- 15520453
TI  - Removal of chylomicron remnants in transgenic mice overexpressing normal and
      membrane-anchored hepatic lipase.
AB  - The LDL receptor and the LDL receptor-related protein (LRP) mediate the removal
      of chylomicron remnants. The LRP pathway involves sequestration of particles in
      the space of Disse. It has been proposed that either alone or in combination with
      other factors, such as apolipoprotein E and proteoglycans, hepatic lipase (HL)
      may contribute to the sequestration of chylomicron remnants. To test this
      hypothesis, we generated two lines of transgenic mice producing rat HL as a
      native or as a membrane-anchored form. These animals express HL at levels similar
      to normal rat. Chylomicron remnants were perfused in a single nonrecirculating
      pass into the livers of the rat HL transgenic, HL-deficient, and wild-type (WT)
      mice for 20 min, and the rate of chylomicron remnant removal was measured.
      Chylomicron remnants were removed at a rate of approximately 50% per pass in WT
      mice. It was slightly increased in both transgenic mice and reduced in HL
      deficient mice compared with the WT mice. Confocal microscopy of liver sections
      showed that a modest amount of HL colocalized with chylomicron remnant clusters
      in the transgenic mice, suggesting that HL is a component of the LRP-proteoglycan
      clusters. These data suggest that HL helps to direct cholesterol to the tissues
      in which it is localized by a nonenzymatic mechanism.

PMID- 15520455
TI  - An improved assay for platelet-activating factor using HPLC-tandem mass
      spectrometry.
AB  - We describe an improved assay for platelet-activating factor (PAF; 1-O-alkyl-2
      acetyl-sn-glycero-3-phosphocholine) using HPLC-tandem mass spectrometry (LC
      MS/MS). The present method can readily detect as little as 1 pg (1.9 fmol) of
      PAF, a significant improvement over previously described LC-MS/MS methods, and
      gives a linear response up to 1,000 pg of PAF. Our method also overcomes the
      artifacts from isobaric lipids that have limited the usefulness of certain
      existing LC-MS/MS assays for PAF. In the course of these studies, we detected
      three novel lipid species in human neutrophils. One of the novel lipids appears
      to be a new molecular species of PAF, and the other two have chromatographic and
      mass spectrometric properties consistent with stearoyl-formyl
      glycerophosphocholine and oleoyl-formyl-glycerophosphocholine. These observations
      identify previously unknown potential interferences in the measurement of PAF by
      LC-MS/MS. Moreover, our data suggest that the previously described palmitoyl
      formyl-glycerophosphocholine is not unique but rather is a member of a new and
      poorly understood family of formylated lipids.

PMID- 15520456
TI  - Demethylation using the epigenetic modifier, 5-azacytidine, increases the
      efficiency of transient transfection of macrophages.
AB  - This study was aimed at developing a method for high-efficiency transient
      transfection of macrophages. Seven methods were evaluated for transient
      transfection of murine macrophage RAW 264.7 cells. The highest transfection
      efficiency was achieved with DEAE-dextran, although the proportion of cells
      expressing the reporter gene did not exceed 20%. It was subsequently found that
      the cytomegalovirus plasmid promoter in these cells becomes methylated. When
      cells were treated with the methylation inhibitor 5-azacytidine, methylation of
      the plasmid promoter was abolished and a dose-dependent stimulation of reporter
      gene expression was observed with expression achieved in more than 80% of cells.
      Treatment of cells with 5-azacytidine also caused increased efficiency of
      transfection of macrophages with plasmids driven by RSV, SV40, and EF-1alpha
      promoters and transient transfection of human HepG2 cells. Inhibition of
      methylation also increased the amount and activity of sterol 27-hydroxylase
      (CYP27A1) detected in RAW 264.7 cells transfected with a CYP27A1 expression
      plasmid. Treatment of cells with 5-azacytidine alone did not affect either
      cholesterol efflux from nontransfected cells or expression of ABCA1 and CYP27A1.
      However, transfection with CYP27A1 led to a 2- to 4-fold increase of cholesterol
      efflux. We conclude that treatment with 5-azacytidine can be used for high
      efficiency transient transfection of macrophages.

PMID- 15520457
TI  - Laminin-5 promotes cell motility by regulating the function of the integrin
      alpha6beta1 in pancreatic cancer.
AB  - The authors have found that a result reported in the above paper is not
      reproducible and wish to withdraw it from publication. The paper has been
      published online in Carcinogenesis Advance Access and the authors hereby retract
      this paper and discourage citations of it.

PMID- 15520458
TI  - Cancer siRNA therapy by tumor selective delivery with ligand-targeted sterically
      stabilized nanoparticle.
AB  - Potent sequence selective gene inhibition by siRNA 'targeted' therapeutics
      promises the ultimate level of specificity, but siRNA therapeutics is hindered by
      poor intracellular uptake, limited blood stability and non-specific immune
      stimulation. To address these problems, ligand-targeted, sterically stabilized
      nanoparticles have been adapted for siRNA. Self-assembling nanoparticles with
      siRNA were constructed with polyethyleneimine (PEI) that is PEGylated with an Arg
      Gly-Asp (RGD) peptide ligand attached at the distal end of the polyethylene
      glycol (PEG), as a means to target tumor neovasculature expressing integrins and
      used to deliver siRNA inhibiting vascular endothelial growth factor receptor-2
      (VEGF R2) expression and thereby tumor angiogenesis. Cell delivery and activity
      of PEGylated PEI was found to be siRNA sequence specific and depend on the
      presence of peptide ligand and could be competed by free peptide. Intravenous
      administration into tumor-bearing mice gave selective tumor uptake, siRNA
      sequence-specific inhibition of protein expression within the tumor and
      inhibition of both tumor angiogenesis and growth rate. The results suggest
      achievement of two levels of targeting: tumor tissue selective delivery via the
      nanoparticle ligand and gene pathway selectivity via the siRNA oligonucleotide.
      This opens the door for better targeted therapeutics with both tissue and gene
      selectivity, also to improve targeted therapies with less than ideal therapeutic
      targets.

PMID- 15520459
TI  - Pattern of genes influenced by conditional expression of the transcription
      factors HNF6, HNF4alpha and HNF1beta in a pancreatic beta-cell line.
AB  - Using the rat insulinoma cell line INS-1 we generated beta-cell clones that are
      most efficient for gene transfer, as they contain an FRT site for Flp recombinase
      mediated, site-directed integration of a single copy transgene. Therefore, the
      gene-of-interest can be introduced by DNA transfection without the need to select
      individual cell clones. Additionally, the clones contain the tetracycline
      repressor allowing tetracycline induction of the transgene. By oligonucleotide
      microarray we define the beta-cell specific phenotype of the Flp-In T-REx cell
      clones. Using a clone expressing the HNF6, HNF4alpha and HNF1beta transcription
      factors at a limited level, we introduced the expression vectors encoding these
      factors. We show efficient tetracycline induction of these transcription factors
      by western blots and immunocytochemistry. Microarrays reveal that these three
      factors affect a similar number of genes with only few genes regulated in common.
      Statistical analysis reveals that the three transcription factors affect genes
      categorized to different biological processes. Furthermore, we document the
      usefulness of these Flp-In T-REx cells for the functional analysis of mutated
      HNF1beta transcription factors found in human MODY5 patients. We show that the
      expression of the mutant P328L329del and A263insGG affects only very few
      transcripts and these are predominantly distinct from those induced by wild-type
      HNF1beta.

PMID- 15520460
TI  - Quantitative sequential chromatin immunoprecipitation, a method for analyzing co
      occupancy of proteins at genomic regions in vivo.
AB  - Sequential chromatin immunoprecipitation (SeqChIP) is a procedure in which
      formaldehyde-crosslinked, protein-DNA complexes from living cells are subjected
      to two sequential immunoprecipitations with antibodies of different specificity.
      SeqChIP has been used to address, in a qualitative manner, whether two proteins
      can simultaneously co-occupy a stretch of DNA in vivo. Here, we expand on our
      earlier work and describe theoretical and practical considerations for performing
      and interpreting SeqChIP experiments in a quantitative manner. We provide a
      detailed experimental procedure for designing and performing SeqChIP experiments
      as well as experimental examples of the three possible outcomes: full co
      occupancy, no co-occupancy and partial co-occupancy. In some cases of partial co
      occupancy, the order of immunoprecipitations in SeqChIP can strongly influence
      the outcome. We experimentally confirm a quantitative parameter that provides a
      measure of co-occupancy of two proteins on a given region of DNA and provide
      information on how to interpret the results of SeqChIP experiments. Our
      quantitative treatment of SeqChIP data substantially expands the usefulness of
      the technique for elucidating molecular mechanisms in vivo.

PMID- 15520461
TI  - Small circular DNAs for synthesis of the human telomere repeat: varied sizes,
      structures and telomere-encoding activities.
AB  - We describe the construction, structural properties and enzymatic substrate
      abilities of a series of circular DNA oligonucleotides that are entirely composed
      of the C-rich human telomere repeat, (CCCTAA)n. The nanometer-sized circles range
      in length from 36 to 60 nt, and act as templates for synthesis of human telomere
      repeats in vitro. The circles were constructed successfully by the application of
      a recently developed adenine-protection strategy, which allows for
      cyclization/ligation with T4 DNA ligase. Thermal denaturation studies showed that
      at pH 5.0, all five circles form folded structures with similar stability, while
      at pH 7.0 no melting transitions were seen. Circular dichroism spectra at the two
      pH conditions showed evidence for i-motif structures at the lower pH value. The
      series was tested as rolling circle templates for a number of DNA polymerases at
      pH = 7.3-8.5, using 18mer telomeric primers. Results showed that surprisingly
      small circles were active, although the optimum size varied from enzyme to
      enzyme. Telomeric repeats >>1000 nt in length could be synthesized in 1 h by the
      Klenow (exo-) DNA polymerase. The results establish a convenient way to make long
      human telomeric repeats for in vitro study of their folding and interactions, and
      establish optimum molecules for carrying this out.

PMID- 15520462
TI  - Site-selective and hydrolytic two-strand scission of double-stranded DNA using
      Ce(IV)/EDTA and pseudo-complementary PNA.
AB  - By combining Ce(IV)/EDTA with two pseudo-complementary peptide nucleic acids
      (pcPNAs), both strands in double-stranded DNA were site-selectively hydrolyzed at
      the target site. Either plasmid DNA (4361 bp) or its linearized form was used as
      the substrate. When two pcPNAs invaded into the double-stranded DNA, only the
      designated portion in each of the two strands was free from Watson-Crick base
      pairing with the counterpart DNA or the pcPNA. Upon the treatment of this
      invasion complex with Ce(IV)/EDTA at 37 degrees C and pH 7.0, both of these
      single-stranded portions were selectively hydrolyzed at the designated site,
      resulting in the site-selective two-strand scission of the double-stranded DNA.
      Furthermore, the hydrolytic scission products were successfully connected with
      foreign double-stranded DNA by using ligase. The potential of these artificial
      systems for manipulation of huge DNA has been indicated.

PMID- 15520463
TI  - Optical absorption assay for strand-exchange reactions in unlabeled nucleic
      acids.
AB  - The nucleic acid exchange reaction is a common feature for genetic recombination,
      DNA replication and transcription. Due to the fact that in the strand-exchange
      reactions the reactant and product molecules have similar or identical nucleotide
      sequences, the reaction is undetectable. As a rule, the nucleic acids with
      radioactive or fluorescence labels are used in such studies. Besides the fact
      that the labels can perturb the reaction and pose a health risk to the
      investigators, the assays usually involve extra experimental steps: quenching the
      reaction, separation, visualization and quantification of the products. Here, we
      describe a straightforward, direct and precise method to study strand-exchange
      reaction of unlabeled nucleic acids by real-time measurements of optical
      absorption. The method takes advantage of the property of some guanine-rich
      oligonucleotides to adopt monomolecular quadruplex conformation in the presence
      of certain cations. The conformation is characterized by significant absorption
      in long-wavelength range of the ultraviolet region where usually other secondary
      structures are transparent. The 'signal' oligonucleotide is incorporated into
      reactant duplex by annealing with target sequence. Adding the replacement
      sequence initiates the release of the 'signal' oligonucleotide into solution,
      which is accompanied by ultraviolet absorption in long-wavelength range.

PMID- 15520464
TI  - Complex patterns of transcription at the insertion site of a retrotransposon in
      the mouse.
AB  - Here we report that transcriptional effects of the insertion of a retrotransposon
      can occur simultaneously both upstream and downstream of the insertion site. We
      have identified an intra-cisternal A particle (IAP) retrotransposon in intron 6
      of a gene that we have named Cabp (CDK5 activator binding protein). The presence
      of the IAP is associated with an aberrant transcript initiating from a cryptic
      promoter in the IAP, reading out into the adjacent Cabp gene sequence. The
      expression of this transcript is highly variable among isogenic mice within the
      C57BL/6J strain and so Cabp(IAP) can be classified as a metastable epiallele. As
      expected, the presence or absence of the transcript correlates with differential
      DNA methylation of the 5' LTR of the IAP. More surprisingly, in mice where the
      retrotransposon is unmethylated and presumably transcriptionally active, we find
      a number of short Cabp transcripts which initiate at the normal 5' end of the
      gene but terminate prematurely, just 5' of the retrotransposon. This is the first
      report of a retrotransposon having both upstream and downstream effects on
      transcription at the site of insertion and it suggests that alternative
      polyadenylation may sometimes be caused by a downstream convergent transcription
      unit.

PMID- 15520465
TI  - Cleavage of double-stranded RNA by RNase HI from a thermoacidophilic archaeon,
      Sulfolobus tokodaii 7.
AB  - ST0753, the orthologous gene of Type 1 RNase H found in a thermoacidophilic
      archaeon, Sulfolobus tokodaii, was analyzed. The recombinant ST0753 protein
      exhibited RNase H activity in both in vivo and in vitro assays. The protein
      expressed in an RNase H-deficient mutant Escherichia coli strain functioned to
      suppress the temperature-sensitive phenotype associated with the lack of RNase H.
      The in vitro characteristics of the gene's RNase H activity were similar to those
      of Halobacterium RNase HI, the first archaeal Type 1 RNase H to be characterized.
      Surprisingly, the S.tokodaii RNase HI cleaved not only the RNA strand of an
      RNA/DNA hybrid but also an RNA strand of an RNA/RNA duplex in the presence of
      Mn2+ or Co2+. The result of gel filtration column chromatography showed this
      double-stranded RNA-dependent RNase (dsRNase) activity was coincident with
      S.tokodaii RNase HI. A site-directed mutagenesis study of essential amino acids
      for RNase H activity indicated that this activity also affected dsRNase activity.
      A single amino acid replacement of Asp-125 by Asn resulted in loss of dsRNase
      activity but not RNase H activity, suggesting that amino acid residues required
      for dsRNase activity seemed slightly different from those of RNase H activity.
      Some reverse transcriptases from retroelements can cleave double-stranded RNA,
      and this activity requires the RNase H domain. Similarities in primary structure
      and biochemical characteristics between S.tokodaii RNase HI and reverse
      transcriptases imply that the S.tokodaii enzyme might be derived from the RNase H
      domain of reverse transcriptase.

PMID- 15520466
TI  - Core promoter elements of eukaryotic genes have a highly distinctive mechanical
      property.
AB  - In spite of the abundant data on DNA sequence, the mechanical aspects of promoter
      DNA remain poorly understood. We classified 1871 human and 196 mouse RNA
      polymerase II promoters and investigated average flexibility profiles of the
      human promoters containing either a TATA box or an initiator (Inr) sequence only.
      Here, we show that TATA boxes and Inr sequences have a common anomalous
      mechanical property: they are comprised of distinctively flexible and rigid
      sequences, compared with the other parts of the promoter region. The +2 position
      in the Inr consensus sequence does not favor adenine to keep the high flexibility
      and thus this position is more accurately represented as 'T, G, C>>A'.
      Additionally, it was also found that DNA region upstream of TATA box or Inr
      sequence is more rigid than region downstream of each element. These properties
      may function as a marker for recognition by TATA-binding protein and Inr-binding
      protein.

PMID- 15520467
TI  - Alleviation of restriction by DNA condensation and non-specific DNA binding
      ligands.
AB  - During conditions of cell stress, the type I restriction and modification enzymes
      of bacteria show reduced, but not zero, levels of restriction of unmethylated
      foreign DNA. In such conditions, chemically identical unmethylated recognition
      sequences also occur on the chromosome of the host but restriction alleviation
      prevents the enzymes from destroying the host DNA. How is this distinction
      between chemically identical DNA molecules achieved? For some, but not all, type
      I restriction enzymes, alleviation is partially due to proteolytic degradation of
      a subunit of the enzyme. We identify that the additional alleviation factor is
      attributable to the structural difference between foreign DNA entering the cell
      as a random coil and host DNA, which exists in a condensed nucleoid structure
      coated with many non-specific ligands. The type I restriction enzyme is able to
      destroy the 'naked' DNA using a complex reaction linked to DNA translocation, but
      this essential translocation process is inhibited by DNA condensation and the
      presence of non-specific ligands bound along the DNA.

PMID- 15520468
TI  - CTD kinase I is involved in RNA polymerase I transcription.
AB  - RNA polymerase II carboxy terminal domain (CTD) kinases are key elements in the
      control of mRNA synthesis. Yeast CTD kinase I (CTDK-I), is a non-essential
      complex involved in the regulation of mRNA synthesis at the level of
      transcription elongation, pre-mRNA 3' formation and nuclear export. Here, we
      report that CTDK-I is also involved in ribosomal RNA synthesis. We show that CTDK
      I is localized in part in the nucleolus. In its absence, nucleolar structure and
      RNA polymerase I transcription are affected. In vitro experiments show an
      impairment of the Pol I transcription machinery. Remarkably, RNA polymerase I co
      precipitates from cellular extracts with Ctk1, the kinase subunit of the CTDK-I
      complex. In vitro analysis further demonstrates a direct interaction between RNA
      polymerase I and Ctk1. The results suggest that CTDK-I might participate in the
      regulation of distinct nuclear transcriptional machineries, thus playing a role
      in the adaptation of the global transcriptional response to growth signalling.

PMID- 15520469
TI  - Overexpression of human DNA polymerase mu (Pol mu) in a Burkitt's lymphoma cell
      line affects the somatic hypermutation rate.
AB  - DNA polymerase mu (Pol mu) is a DNA-dependent DNA polymerase closely related to
      terminal deoxynucleotidyl transferase (TdT), and prone to induce template/primer
      misalignments and misincorporation. In addition to a proposed general role in non
      homologous end joining of double-strand breaks, its mutagenic potential and
      preferential expression in secondary lymphoid tissues support a role in somatic
      hypermutation (SHM) of immunoglobulin genes. Here, we show that human Pol mu
      protein is expressed in the nucleus of centroblasts obtained from human tonsils,
      forming a characteristic foci pattern resembling that of other DNA repair
      proteins in response to DNA damage. Overexpression of human Pol mu in Ramos
      cells, in which the SHM process is constitutive, augmented the somatic mutations
      specifically at the variable (V) region of the immunoglobulin genes. The nature
      of the mutations introduced, mostly base substitutions, supports the contribution
      of Pol mu to mutation of G and C residues during SHM. In vitro analysis of Pol mu
      misincorporation on specific templates, that mimic DNA repair intermediates and
      correspond to mutational hotspots, indicated that many of the mutations observed
      in vivo can be explained by the capacity of Pol mu to induce transient
      template/primer misalignments.

PMID- 15520470
TI  - Identification of the CRP regulon using in vitro and in vivo transcriptional
      profiling.
AB  - The Escherichia coli cyclic AMP receptor protein (CRP) is a global regulator that
      controls transcription initiation from more than 100 promoters by binding to a
      specific DNA sequence within cognate promoters. Many genes in the CRP regulon
      have been predicted simply based on the presence of DNA-binding sites within gene
      promoters. In this study, we have exploited a newly developed technique, run-off
      transcription/microarray analysis (ROMA) to define CRP-regulated promoters. Using
      ROMA, we identified 176 operons that were activated by CRP in vitro and 16
      operons that were repressed. Using positive control mutants in different regions
      of CRP, we were able to classify the different promoters into class I or class
      II/III. A total of 104 operons were predicted to contain Class II CRP-binding
      sites. Sequence analysis of the operons that were repressed by CRP revealed
      different mechanisms for CRP inhibition. In contrast, the in vivo transcriptional
      profiles failed to identify most CRP-dependent regulation because of the
      complexity of the regulatory network. Analysis of these operons supports the
      hypothesis that CRP is not only a regulator of genes required for catabolism of
      sugars other than glucose, but also regulates the expression of a large number of
      other genes in E.coli. ROMA has revealed 152 hitherto unknown CRP regulons.

PMID- 15520472
TI  - The impact of the Women's Health Initiative study on incident clonidine use in
      Ontario, Canada.
AB  - BACKGROUND: Following publication of the Women's Health Initiative (WHI) study,
      many women discontinued use of estrogen replacement therapy. There is some
      evidence that the antihypertensive agent clonidine can reduce the frequency of
      hot flashes associated with menopause. OBJECTIVES: To determine the impact of the
      WHI study on incident use of clonidine in elderly women in Ontario, Canada.
      METHODS: Retrospective, population-based administrative database design. Data on
      all residents of Ontario over the age of 65 years were included. Time series
      methods were used to analyze change in incident clonidine use following
      publication of the WHI study. RESULTS: Following publication of the WHI study,
      incident use of clonidine increased substantially among elderly women in Ontario,
      Canada. Similar trends were not observed for incident use of other
      antihypertensive medications. CONCLUSION: During a period of time in which a
      large proportion of women discontinued estrogen replacement therapy, incident use
      of clonidine increased. There is some evidence that a small number of women may
      have sought alternative relief from menopausal symptoms using other
      pharmacological therapies.

PMID- 15520471
TI  - Domain organization of the yeast histone chaperone FACT: the conserved N-terminal
      domain of FACT subunit Spt16 mediates recovery from replication stress.
AB  - The abundant nuclear complex termed FACT affects several DNA transactions in a
      chromatin context, including transcription, replication, and repair. Earlier
      studies of yeast FACT, which indicated the apparent dispensability of conserved
      sequences at the N terminus of the FACT subunit Cdc68/Spt16, prompted genetic and
      biochemical studies reported here that suggest the domain organization for Spt16
      and the other FACT subunit Pob3, the yeast homolog of the metazoan SSRP1 protein.
      Our findings suggest that each FACT subunit is a multidomain protein, and that
      FACT integrity depends on Pob3 interactions with the Spt16 Mid domain. The
      conserved Spt16 N-terminal domain (NTD) is shown to be without essential function
      during normal growth, but becomes important under conditions of replication
      stress. Genetic interactions suggest that some functions carried out by the Spt16
      NTD may be partially redundant within FACT.

PMID- 15520473
TI  - Acute coronary syndrome induced by intravenous ephedrine in pregnant woman with
      normal coronaries.
AB  - Intravenous ephedrine administered during a C-section was observed to cause an
      acute coronary syndrome in a pregnant woman with normal coronaries. The patient
      developed sub-sternal chest pain, was noted to have 10 beats of non-sustained
      ventricular tachycardia, ST abnormalities were observed on her ECG and cardiac
      enzymes were elevated. The patient had normal coronary arteries by angiogram and
      during a one-year period of follow up no further cardiac events occurred.

PMID- 15520474
TI  - The economics of adjunctive therapies in coronary angioplasty: drugs, devices, or
      both?
AB  - BACKGROUND: Abciximab reduces the number of ischemic events in patients
      undergoing angioplasty compared to standard therapy. Coronary stenting reduces
      the need for repeat procedures. Abciximab or stents individually are considered
      cost effective interventions. There is a need to quantify the economic value of
      the combination of abciximab and stenting over stenting alone. METHODS: A
      decision analytic model was developed incorporating the outcomes from the
      EPISTENT study. Costs from Canadian sources for hospitalization, procedures and
      medications were used. Life expectancy was estimated using a Markov model. Total
      expected costs and outcomes of the abciximab and stent vs. stent alone were
      compared in an incremental analysis. The perspective of the analysis was a
      Canadian teaching hospital. RESULTS: The acquisition cost for abciximab was
      partially offset by reduced costs for managing clinical events resulting in a net
      incremental cost of 1,076 dollars per patient over one year (8,617 dollars
      combination vs. 7,541 dollars stent alone). This added cost was accompanied by a
      reduction in large MI or death by an absolute rate of 5.7% at one year (5.3%
      combination vs. 11.0% stent alone), yielding an incremental cost-effectiveness
      ratio of 18,877 dollars per death or large MI averted. The long-term survival
      gain was 0.15 to 0.37 years yielding an attractive incremental cost effectiveness
      ratio of 2,832 dollars to 7,173 dollars per life year gained. CONCLUSIONS: The
      combination of abciximab and stenting versus stenting alone provides improved
      clinical outcomes at a very reasonable cost from the Canadian hospital
      perspective.

PMID- 15520475
TI  - The antidepressant effects of risperidone and olanzapine in bipolar disorder.
AB  - OBJECTIVE: To describe the antidepressant effectiveness of olanzapine and
      risperidone and compare their tolerability when employed adjunctively in bipolar
      I/II disorder. METHOD: In an observational study, twenty-one ambulatory subjects
      with DSM-IV defined bipolar I/II disorder, in any phase of the illness, openly
      received adjunctive risperidone or olanzapine. The primary efficacy parameters
      were the Hamilton Depression Rating Scale (HDRS-17) and the Maier and Philips
      Severity Subscale. Secondary efficacy parameters included the Young Mania Rating
      Scale (YMRS) along with the Clinical Global Impressions Scale (CGI). Response was
      defined as a significant change from baseline to endpoint in the total mean HDRS
      17 score. The primary tolerability parameters were the Abnormal Involuntary
      Movement Scale (AIMS) along with changes in weight and body mass index (BMI
      kg/m2). Patients were evaluated prospectively with repeated monthly assessments
      for up to 6 months. RESULTS: Eleven patients openly received risperidone; 10
      received olanzapine adjunctive to either lithium or divalproex. Total mean HDRS
      17 scores significantly decreased from baseline to endpoint in both groups
      (p=0.001), with the mean HDRS-17 total scores falling from 17(SD=3.2) to
      5(SD=1.5) by 6 months in the risperidone-treated group and from 18 (SD=1.9) to 7
      (SD=2.0) in the olanzapine-treated group. Differences between the risperidone
      treated group and the olanzapine-treated group were not significant at 6 months
      (p=0.754). The mean doses of study medication were 2.88 (SD=1.6) mg/day for the
      risperidone-treated group and 12.69 (SD=2.3) mg/day for the olanzapine-treated
      group. Both risperidone and olanzapine were generally well tolerated. No patients
      developed tardive dyskinesia. Significant weight gain was experienced by patients
      in both groups [mean weight gain at endpoint was 5.9 kg in risperidone (p=0.023)
      and 11.3 kg in olanzapine (p=0.001)]. There was a significant difference in
      weight gain between the risperidone-treated group and the olanzapine-treated
      group (p=0.001). CONCLUSIONS: These pilot data, from the first prospective
      comparison study of risperidone and olanzapine in bipolar disorder, suggest that
      adjunctive administration of either agent may reduce depressive symptom severity.
      No subjects receiving risperidone or olanzapine developed tardive dyskinesia.
      Both compounds imparted substantial weight gain with significantly more weight
      gain accrual with olanzapine. As this was an observational study, the
      antidepressant effect and tolerability profile of these compounds requires
      validation via double-blind placebo controlled investigations.

PMID- 15520477
TI  - Tuberculosis research in India.

PMID- 15520476
TI  - Knowledge of safety and herb-drug interations amongst HIV+ individuals: a focus
      group study.
AB  - OBJECTIVE: To determine how HIV+ individuals access safety and knowledge of drug
      interactions related to complementary and alternative medicine (CAM). METHODS: We
      conducted two separate focus group sessions with HIV+ users of complementary
      therapies. A total of 8 men participated at an urban health centre. Focus group
      sessions were audio taped and transcribed verbatim. Analysis was conducted
      independently and in duplicate, using thematic analysis. RESULTS: All focus group
      participants described their use of CAM as very important for their health
      maintenance, giving them a feeling of empowerment in their health care. Potential
      side effects and safety issues were indicated as major concerns for treatment
      decisions, but the participant's knowledge of safety issues involved in CAM care
      for HIV+ patients was limited. The sources used by the participants to gather
      information regarding safety and interactions with medications were varied but
      included: their CAM providers, their physicians, books, resources from AIDS
      Service Organizations, the internet and health food stores. Participants
      acknowledged that appraising the quality of such information is difficult.
      CONCLUSIONS: The participants in this study had a strong trust in CAM and used a
      wide variety of sources to gather information on CAM safety, though their
      knowledge base was poor. As the use of CAM grows, further research on how to
      disseminate reliable information on safety and efficacy to this potentially
      vulnerable population is required.

PMID- 15520478
TI  - Genomics of Mycobacterium tuberculosis: old threats & new trends.
AB  - Tuberculosis (TB) has been declared as a global health emergency by the World
      Health Organization (WHO). This has been mainly due to the emergence of multiple
      drug resistant strains and the synergy between tubercle bacilli and the human
      immunodeficiency virus (HIV). Genomic analysis of strains for outbreak
      investigations is in vogue for about a decade now. However, information available
      from whole genome sequencing efforts and comparative genomics of laboratory and
      field strains is likely to revolutionize efforts towards understanding molecular
      pathogenesis and dissemination dynamics of this dreaded disease. Genomic
      information is also going to fuel discovery projects where new targets will be
      identified and explored towards a new drug for TB. Besides this, efforts of
      information technologists, chemists, population biologists, freelance workers,
      media persons, non-governmental organizations and administrators to needed to
      handle the problem of tuberculosis to prevent it from becoming a pandemic.

PMID- 15520479
TI  - Immunology of tuberculosis.
AB  - Tuberculosis is a major health problem throughout the world causing large number
      of deaths, more than that from any other single infectious disease. The review
      attempts to summarize the information available on host immune response to
      Mycobacterium tuberculosis. Since the main route of entry of the causative agent
      is the respiratory route, alveolar macrophages are the important cell types,
      which combat the pathogen. Various aspects of macrophage-mycobacterium
      interactions and the role of macrophage in host response such as binding of M.
      tuberculosis to macrophages via surface receptors, phagosome-lysosome fusion,
      mycobacterial growth inhibition/killing through free radical based mechanisms
      such as reactive oxygen and nitrogen intermediates; cytokine-mediated mechanisms;
      recruitment of accessory immune cells for local inflammatory response and
      presentation of antigens to T cells for development of acquired immunity have
      been described. The role of macrophage apoptosis in containing the growth of the
      bacilli is also discussed. The role of other components of innate immune response
      such as natural resistance associated macrophage protein (Nramp), neutrophils,
      and natural killer cells has been discussed. The specific acquired immune
      response through CD4 T cells, mainly responsible for protective Th1 cytokines and
      through CD8 cells bringing about cytotoxicity, also has been described. The role
      of CD-1 restricted CD8(+) T cells and non-MHC restricted gamma/deltaT cells has
      been described although it is incompletely understood at the present time.
      Humoral immune response is seen though not implicated in protection. The value of
      cytokine therapy has also been reviewed. Influence of the host human leucocyte
      antigens (HLA) on the susceptibility to disease is discussed. Mycobacteria are
      endowed with mechanisms through which they can evade the onslaught of host
      defense response. These mechanisms are discussed including diminishing the
      ability of antigen presenting cells to present antigens to CD4(+) T cells;
      production of suppressive cytokines; escape from fused phagosomes and inducing T
      cell apoptosis. The review brings out the complexity of the host-pathogen
      interaction and underlines the importance of identifying the mechanisms involved
      in protection, in order to design vaccine strategies and find out surrogate
      markers to be measured as in vitro correlate of protective immunity.

PMID- 15520480
TI  - Molecular epidemiology of tuberculosis.
AB  - Molecular epidemiology (ME), a blend of molecular biology and epidemiology, is
      very useful to study the spread of tubercle bacilli in mini epidemics, outbreaks,
      to analyse the transmission dynamics of tuberculosis (TB) and to determine the
      risk factors for TB transmission in a community. ME has a great role in
      distinguishing between exogenous reinfection and endogenous reactivation. In the
      laboratory, molecular epidemiology can be used to identify cross contamination.
      Many new DNA typing methods have been introduced after the initial introduction
      of restriction fragment length polymorphism (RFLP) in 1993. An internationally
      accepted, standardized protocol for RFLP typing of the Mycobacterium tuberculosis
      complex using IS6110 was published in 1993 and is still used today. Most of the
      newer DNA typing methods are PCR based and microarray based methods are also
      available. This will enable individual strains of M. tuberculosis or clonal
      groups to be identified by specific phenotypic traits. ME will continue to be a
      useful tool in future to measure the impact of any public health intervention
      strategy for control of tuberculosis in the community.

PMID- 15520481
TI  - Epidemiology of tuberculosis: current status in India.
AB  - India is classified along with the sub-Saharan African countries to be among
      those with a high burden and the least prospects of a favourable time trend of
      the disease as of now (Group IV countries). The average prevalence of all forms
      of tuberculosis in India is estimated to be 5.05 per thousand, prevalence of
      smear-positive cases 2.27 per thousand and average annual incidence of smear
      positive cases at 84 per 1,00,000 annually. The credibility and use of the
      estimates are discussed in detail. Reports on recent studies on the time trend of
      the disease from some areas in India, e.g., Chingleput in Tamil Nadu are
      discussed. They confirm the slow downward trend over a fairly long period of
      observation, as in the rural areas around Bangalore. It also outlines the serious
      escalation of disease burden in a tribal population group in Car Nicobar over a
      period 1986-2002, and highlights the nature and extent of the emerging threats.
      Some epidemiologists forecast a rise of 20 per cent in incidence in the next 20
      yr, for India, with a cumulative rise of 46 million cases of tuberculosis during
      that period, largely as a consequence of HIV epidemic. The Governmental efforts
      at intervention through Revised National Tuberculosis Control Programme (RNTCP)
      and at monitoring the epidemiology of intervention through organising routine
      reporting are highlighted, and data are presented and evaluated on these. RNTCP
      needs to be used as an effective instrument to bring a change in epidemiological
      situation, through fast expansion and achievement of global target. The present
      review describes the global tuberculosis situation, and views it in the context
      of the goal of the antituberculosis intervention activities. It presents the
      epidemiological situation in India, comments on the current trend and discusses
      the efforts taken towards making projections on the likely burden of disease in
      India over time.

PMID- 15520482
TI  - Epidemiology of HIV-TB in Asia.
AB  - Tuberculosis (TB) has, for centuries, continued to remain a public health problem
      of enormous importance, particularly in the developing world, taking a heavy toll
      of those at their prime of life. The emergence of human immunodeficiency virus
      (HIV infection) and its close association with TB poses an even greater challenge
      to the health systems in general and TB programmes in particular, in African and
      Asian countries. HIV is considered to be the most potent risk factor for
      progression to active TB among those infected both with TB and HIV; as a result,
      TB is the most common life threatening opportunistic infection associated with
      HIV, and biggest cause of death among patients with acquired immunodeficiency
      syndrome (AIDS). In areas hard-hit by HIV, TB is increasing, leading to greater
      case load, thereby overstretching the already fragile health infrastructure. The
      deadly relationship between HIV and TB, each potentiating the effect of the
      other, requires a clearly defined strategy taking into consideration the natural
      history of the co-infection and its progression to clinical TB (and AIDS). It is
      clear that the only way to fight this is by bringing the two programmes to join
      forces and work creatively and innovatively. The strategy should include not only
      preventing HIV through community-based behavioural interventions and limiting
      progression to clinical TB through the use of isoniazid preventive therapy, but
      also early diagnosis and treatment of HIV-associated TB and AIDS using DOTS
      strategy and combination antiretroviral therapy respectively. The strategy
      probably would not succeed unless both the programmes are first strengthened
      before attempting to forge collaboration based on mutual strengths and
      comparative advantages. In addition, mobilizing national and international
      response, building partnerships and mobilizing resources will help a great deal
      in mounting an appropriate and effective response to HIV/TB in the Asian context.

PMID- 15520483
TI  - Infections due to non-tuberculous mycobacteria (NTM).
AB  - The membership list of genus mycobacterium is ever expanding and it has grown to
      95 in year 2003. While leprosy and tuberculosis are specific diseases caused by
      mycobacteria, other members are usually saprophytes but can be opportunistic and
      at times deadly pathogens. These other mycobacteria are referred to as atypical
      mycobacteria, non-tuberculous mycobacteria (NTM) or mycobacteria other than
      tubercle bacilli (MOTT). These organisms can produce localized disease in the
      lungs, lymph glands, skin, wounds or bone. Occasionally they may produce
      disseminated disease. Of the more than 90 known species of NTM, about one third
      have been associated with disease in humans. The species causing human disease
      are : Mycobacterium avium, M. intracellulare, M. kansasii, M. paratuberculosis,
      M. scrofulaceum, M. simiae, M. habana, M. interjectum, M. xenopi, M.
      heckeshornense, M. szulgai, M. fortuitum, M. immunogenum, M. chelonae, M.
      marinum, M. genavense, M. haemophilum, M. celatum, M. conspicuum, M. malmoense,
      M. ulcerans, M. smegmatis, M. wolinskyi, M. goodii, M. thermoresistible, M.
      neoaurum, M. vaccae, M.palustre, M. elephantis, M. bohemicam and M. septicum.
      Isolation of these mycobacteria from representative specimens and their rapid
      identification is very important as the treatment strategy for tuberculosis and
      other mycobacterioses is different. Several biochemical, chemical (lipid) and
      molecular techniques have been developed for rapid identification of these
      species. Along with suggestive clinical features, poor response to antitubercular
      treatment and repeated isolation of the organisms from the clinical specimens
      these techniques can help in establishing correct diagnosis. Further, many drugs
      like rifampicin, rifabutin, ethambutol, clofazimine, amikacin, new generation
      quinolones and macrolides effective against mycobacterial infections are
      available that can be used in appropriate combinations and dosage to treat these
      infections.

PMID- 15520484
TI  - Abdominal tuberculosis.
AB  - Tuberculosis can involve any part of the gastrointestinal tract and is the sixth
      most frequent site of extrapulmonary involvement. Both the incidence and severity
      of abdominal tuberculosis are expected to increase with increasing incidence of
      HIV infection. Tuberculosis bacteria reach the gastrointestinal tract via
      haematogenous spread, ingestion of infected sputum, or direct spread from
      infected contiguous lymph nodes and fallopian tubes. The gross pathology is
      characterized by transverse ulcers, fibrosis, thickening and stricturing of the
      bowel wall, enlarged and matted mesenteric lymph nodes, omental thickening, and
      peritoneal tubercles. Peritoneal tuberculosis occurs in three forms : wet type
      with ascitis, dry type with adhesions, and fibrotic type with omental thickening
      and loculated ascites. The most common site of involvement of the
      gastrointestinal tuberculosis is the ileocaecal region. Ileocaecal and small
      bowel tuberculosis presents with a palpable mass in the right lower quadrant
      and/or complications of obstruction, perforation or malabsorption especially in
      the presence of stricture. Rare clinical presentations include dysphagia,
      odynophagia and a mid oesophageal ulcer due to oesophageal tuberculosis,
      dyspepsia and gastric outlet obstruction due to gastroduodenal tuberculosis,
      lower abdominal pain and haematochezia due to colonic tuberculosis, and annular
      rectal stricture and multiple perianal fistulae due to rectal and anal
      involvement. Chest X-rays show evidence of concomitant pulmonary lesions in less
      than 25 per cent of cases. Useful modalities for investigating a suspected case
      include small bowel barium meal, barium enema, ultrasonography, computed
      tomographic scan and colonoscopy. Ascitic fluid examination reveals straw
      coloured fluid with high protein, serum ascitis albumin gradient less than 1.1
      g/dl, predominantly lymphocytic cells, and adenosine deaminase levels above 36
      U/l. Laparoscopy is a very useful investigation in doubtful cases. Management is
      with conventional antitubercular therapy for at least 6 months. The recommended
      surgical procedures today are conservative and a period of preoperative drug
      therapy is controversial.

PMID- 15520485
TI  - Extrapulmonary tuberculosis.
AB  - Extrapulmonary involvement can occur in isolation or along with a pulmonary focus
      as in the case of patients with disseminated tuberculosis (TB). The recent human
      immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS)
      pandemic has resulted in changing epidemiology and has once again brought
      extrapulmonary tuberculosis (EPTB) into focus. EPTB constitutes about 15 to 20
      per cent of all cases of tuberculosis in immunocompetent patients and accounts
      for more than 50 per cent of the cases in HIV-positive individuals. Lymph nodes
      are the most common site of involvement followed by pleural effusion and
      virtually every site of the body can be affected. Since the clinical presentation
      of EPTB is atypical, tissue samples for the confirmation of diagnostic can
      sometimes be difficult to procure, and the conventional diagnostic methods have a
      poor yield, the diagnosis is often delayed. Availability of computerised
      tomographic scan, magnetic resonance imaging laparoscopy, endoscopy have
      tremendously helped in anatomical localisation of EPTB. The disease usually
      responds to standard antituberculosis drug treatment. Biopsy and/or surgery is
      required to procure tissue samples for diagnosis and for managing complications.
      Further research is required for evolving the most suitable treatment regimens,
      optimal duration of treatment and safety when used with highly active
      antiretroviral treatment (HAART).

PMID- 15520486
TI  - Multidrug-resistant tuberculosis.
AB  - Multidrug-resistant tuberculosis (MDR-TB) caused by Mycobacterium tuberculosis
      resistant to both isoniazid and rifampicin with or without resistance to other
      drugs is among the most worrisome elements of the pandemic of antibiotic
      resistance. Globally, about three per cent of all newly diagnosed patients have
      MDR-TB. The proportion is higher in patients who have previously received
      antituberculosis treatment reflecting the failure of programmes designed to
      ensure complete cure of patients with tuberculosis. While host genetic factors
      may probably contribute, incomplete and inadequate treatment is the most
      important factor leading to the development of MDR-TB. The definitive diagnosis
      of MDR-TB is difficult in resource poor low income countries because of non
      availability of reliable laboratory facilities. Efficiently run tuberculosis
      control programmes based on directly observed treatment, short-course (DOTS)
      policy is essential for preventing the emergence of MDR-TB. Management of MDR-TB
      is a challenge which should be undertaken by experienced clinicians at centres
      equipped with reliable laboratory service for mycobacterial culture and in vitro
      sensitivity testing as it requires prolonged use of expensive second-line drugs
      with a significant potential for toxicity. Judicious use of drugs, supervised
      individualised treatment, focussed clinical, radiological and bacteriological
      follow up, use of surgery at the appropriate juncture are key factors in the
      successful management of these patients. In certain areas, currently available
      programme approach may not be adequate and innovative approaches such as DOTS
      plus may have to be employed to effectively control MDR-TB.

PMID- 15520487
TI  - Drug resistance in tuberculosis in India.
AB  - The current global concern in the treatment of tuberculosis (TB) is the emergence
      of resistance to the two most potent drugs viz., isoniazid and rifampicin. The
      level of initial drug resistance is an epidemiological indicator to assess the
      success of the TB control programme. Though drug resistance in TB has frequently
      been reported from India, most of the available information is localized, sketchy
      or incomplete. A review of the few authentic reports indicates that there is no
      clear evidence of an increase in the prevalence of initial resistance over the
      years. However, a much higher prevalence of acquired resistance has been reported
      from several regions, though based on smaller numbers of patients. A strong TB
      control programme and continuous surveillance studies employing standardized
      methodology and rigorous quality control measures will serve as useful parameters
      in the evaluation of current treatment policies as well as the management of
      multidrug resistant (MDR) TB cases.

PMID- 15520488
TI  - Some current concepts on childhood tuberculosis.
AB  - As children acquire infection with Mycobacterium tuberculosis from adults in
      their environment, the epidemiology of childhood tuberculosis (TB) follows that
      in adults. While global burden of childhood tuberculosis is unclear, in
      developing countries the annual risk of tuberculosis infection in children is 2-
      5 per cent. Nearly 8-20 per cent of the deaths caused by tuberculosis occur in
      children. It has been suggested that BCG vaccination is responsible for decrease
      in the occurrence of disseminated and severe disease. Localized forms of illness,
      e.g., intrathoracic lymphadenopathy, and localized CNS disease have been reported
      to occur with greater frequency in vaccinated children. Human immunodeficiency
      virus (HIV) infected children are at an increased risk of tuberculosis,
      particularly disseminated disease. Diagnosis of TB in children presents special
      problems as the sputum is generally not available for examination. Diagnostic
      algorithms include scoring system utilizing clinical parameters and results of
      investigations. Various diagnostic techniques such as improved culture
      techniques, serodiagnosis, and nucleic acid amplification have been developed and
      evaluated to improve diagnosis of childhood tuberculosis. Serodiagnosis is an
      attractive investigation but till date none of the tests showed desirable
      sensitivity and specificity. Tests based on nucleic acid amplification are a
      promising development. Relatively less experience in children, need for technical
      expertise and high cost are the limiting factors for their use in childhood
      tuberculosis. Short-course chemotherapy for childhood tuberculosis is well
      established. Treatment with intermittent regimens is comparable to daily
      regimens. Directly observed treatment strategy (DOTS) has also shown encouraging
      results. Pattern of drug resistance among children with TB tends to reflect those
      found among adults in the same population. The rates of drug resistance to any
      drug vary from 20 to 80 per cent in different geographic regions.

PMID- 15520489
TI  - Current trends in chemotherapy of tuberculosis.
AB  - After treptomycin, which heralded the era of antibacterial chemotherapy for
      tuberculosis (TB), many important advances have made available treatment regimens
      that are almost 100 per cent curative. Randomised clinical trials by the
      Tuberculosis Research Centre, in Chennai and British Medical Research Council in
      East Africa and in the Far East have helped to establish many of the principles
      of antituberculosis chemotherapy. With successes have also come fresh challenges.
      Mycobacterium tuberculosis becomes rapidly resistant to the drugs used against it
      and in the last decade, the HIV epidemic has had an adverse impact on the global
      epidemiology of tuberculosis, with many countries in Sub-Saharan Africa
      experiencing a 2-3 fold increase in their TB burden. While the currently
      recommended treatment regimens are very effective, they have failed to control
      the burden of TB in the developing countries due to less than satisfactory
      implementation of the control programmes. Faced with the dual threat of multidrug
      resistant TB and the HIV/facilitated increase in TB, the WHO has instituted a
      Global TB Control Programme based on the directly observed treatment shortcourse
      (DOTS) strategy. Much of the principles of this strategy have come out of
      research in India. As part of this strategy, the Government of India is
      implementing a Revised National Tuberculosis Control Programme (RNTCP). Under the
      RNTCP standardized treatment regimens are prescribed for different treatment
      categories. Already more than 80 per cent of the population is covered by this
      Programme and full coverage is slated for 2005. Meanwhile, fresh research is
      ongoing to shorten treatment duration, a measure that should greatly aid TB
      control.

PMID- 15520490
TI  - Newer diagnostic techniques for tuberculosis.
AB  - Diagnosis of tuberculosis is mainly based on clinical features, histopathology,
      demonstration of acid fast bacilli (AFB) and isolation of Mycobacterium
      tuberculosis from the clinical specimens. These techniques have limitations of
      speed, sensitivity and specificity. During the last two decades several rapid
      techniques for detection of early growth (5-14 days as compared to 2-8 wk with
      conventional methods) have been described which can help in obtaining the culture
      and sensitivity reports relatively early. Prominent among such methods are
      BACTEC, mycobacterial growth indicator tuber (MGIT), Septi-chek, MB/ BacT
      systems. This growth can be established by rapid methods based on lipid analysis
      and specific gene probes, PCR-RFLP methods and ribosomal RNA sequencing. Advances
      in knowledge about genetic structure of tubercle bacillus helped develop gene
      probes and gene amplification methods for identification and detection of
      tubercle bacillus, from culture or directly in clinical specimens and molecular
      detection of drug resistance. While the gene probes can help in rapid
      identification of isolates, gene amplification methods (PCR as well as
      isothermal) developed for diagnosis of tuberculosis are demonstrably highly
      sensitive specially in culture negative specimens from different paucibacillary
      forms of disease. With these molecular methods drug resistant mutants for drugs
      like rifampicin can be detected with reasonable certainty within hours. These
      gene probes, gene amplification methods and in situ approaches offer unparalleled
      capability to enhance the diagnosis of tuberculosis in near future.

PMID- 15520492
TI  - Calcium channel antagonists attenuate cross-sensitization to the locomotor
      effects of nicotine and ethanol in mice.
AB  - The present study was focused on evaluation of locomotor cross-sensitization
      between nicotine and ethanol in mice. First, we demonstrated that, after 5 daily
      injections, nicotine (0.5 mg/kg, ip) produced sensitization to its own locomotor
      stimulant effect. Moreover, nicotine-experienced mice manifested an enhanced
      response to ethanol challenge (2 g/kg, ip) indicating the development of cross
      sensitization between nicotine and ethanol in mice. Additionally, the L-type
      voltage-dependent calcium channel antagonists: verapamil and diltiazem, but not
      nimodipine, at the dose of 20 mg/kg, injected before the ethanol challenge,
      blocked the expression of this cross-sensitization. These findings support the
      hypothesis that similar neural calcium-dependent mechanisms are involved in the
      sensitization to locomotor stimulant effects of nicotine and ethanol and point to
      certain differences in acute behavioral effects of various classes of calcium
      channel inhibitors.

PMID- 15520491
TI  - Age-dependent effects of 5,7-dihydroxytryptamine on serotonin transporter in
      different brain areas in the rat.
AB  - In the present study, we investigated the [(3)H]citalopram binding using a
      quantitative autoradiography following intracerebroventricular injection of 5,7
      dihydroxytryptamine (5,7-DHT) in neonatal and adult male Wistar rats. One group
      of animals was injected with 5,7-DHT at 3 days after birth while the second group
      received the neurotoxin at 3 months after birth. Control group was injected with
      saline. Afterwards, all rats were examined at 4(th) months after birth to
      determine the serotonin (5-HT) and catecholamines concentrations using the liquid
      chromatography with electrochemical detection HPLC system and distribution and
      density of [(3)H]citalopram binding sites in the brain using the quantitative
      autoradiography. A marked depletion of brain 5-HT was observed in rats lesioned
      either in postnatal or adult period of life. Rats lesioned in their adult period
      of life showed dramatic reduction of 5-HT transporter in all investigated brain
      areas (i.e.the frontal cortex, entorhinal cortex, hippocampus, caudate-putamen,
      nucleus accumbens and ventral tegmental area). On the other hand, administration
      of 5,7-DHT to newborn rats failed to reduce 5-HT transporter sites in the ventral
      tegmental area, and produced only slight or moderate reduction in the nucleus
      accumbens. Thus, it appears that the mesolimbic ventral tegmental area-nucleus
      accumbens systems are relatively more resistant to 5,7-DHT neurotoxicity in the
      early postnatal period.

PMID- 15520493
TI  - Effect of chronic treatment with dexamethasone on brain dopamine receptors in
      mice.
AB  - Glucocorticoids are expressed in the central nervous system. Radioligand binding
      studies have shown their presence in the neurons of the limbic system, a
      structure involved in mood control and subtle regulation of hypothalamic
      pituitary-adrenal (HPA) axis. Structures of the limbic system are also rich in
      dopaminergic innervation. It has been hypothesized that glucocorticoids may be
      important in causing and perpetuating depression. Our previous study has
      demonstrated that dexamethasone decreases the locomotor activity of mice and
      counteracts the hyperactivity induced by agonists of dopamine receptors. The aim
      of the present study was to find the possible mechanism responsible for these
      behavioral effects of dexamethasone. So we sought to examine the influence of
      chronic dexamethasone treatment on selective radioligand binding to dopamine D(1)
      ([(3)H]SCH 23390) and D(2) ([(3)H]spiperone) receptors in the brain of mice. The
      male Albino Swiss mice received dexamethasone (4, 8 or 16 mg/kg/day) for 14 days.
      The striatum and limbic system structures were isolated and the binding procedure
      was performed 3.5 or 48 h after the last injection. It was shown that 3.5 h after
      the last dose of dexamethasone (4 mg/kg/day), specific D(2) receptor binding was
      statistically significantly increased (by 64%) in the limbic system. On the
      contrary, the tendency to the reduction of specific D(2) receptor binding was
      observed in the striatum. Dexamethasone treatment did not influence the specific
      binding to D(1) receptors in any structure of the brain.

PMID- 15520494
TI  - Pertussis toxin-sensitive G protein modulates the ability of histamine to
      stimulate cAMP production in the chick pineal gland.
AB  - Histamine (HA) is a potent stimulator of cAMP synthesis in various structures of
      chick brain, including the pineal gland. The action of HA is mediated by
      specific, membrane bound H(2)-like receptors, whose pharmacological profile is
      different from that described for H(2) receptors in mammalian tissues. In this
      work, we analyzed the effects of cholera toxin (CTX) and pertussis toxin (PTX),
      well-known modulators of G(s) and G(i)/G(o) protein, respectively, on the
      stimulatory action of HA on cAMP synthesis in the chick pineal gland organ
      cultures. HA and its two biologically active methylated derivatives, 2-methylHA
      and 4-methylHA, markedly increased cAMP content in the chick pineal glands.
      Pretreatment of the chick pineal glands with CTX potently stimulated basal cAMP
      production. In CTX-pretreated glands, elevations of cAMP synthesis evoked by HA,
      2-methylHA and 4-methylHA were additive to those produced by CTX, which is an
      observation suggesting that H(2)-like HA receptors in the chicken pineal gland
      are not coupled to G(s) proteins. Pretreatment of the chick pineal glands with
      PTX significantly enhanced the stimulatory effect of HA and, to a greater extent,
      2-methylHA on cAMP production. The enhancing action of PTX on the HA-evoked cAMP
      formation was not modified by mepyramine, a selective H(1)-type HA receptor
      antagonist. It is suggested that in the chick pineal gland, a population of HA
      receptors is coupled to G(i) (or G(o)) protein. Stimulation of these receptors
      would tonically suppress the activity of the cAMP generating system functionally
      linked to H(2)-like HA receptors.

PMID- 15520495
TI  - Influence of dopamine on flash visual evoked potentials (FVEP) in prenatally
      mercury intoxicated rats.
AB  - The female adult white Wistar rats were given tap water (control) or 50 ppm of
      methylmercury chloride (MMC) ad libitum throughout their pregnancies. Newborn
      rats drank mother's milk during the first 21 days after delivery and then only
      tap water. The study was carried out on three-month old offsprings of white
      Wistar rats. The flash visual evoked potentials (FVEP) were recorded before and
      after injecting of 10 microl 0.9% saline, 50 or 100 nmols of dopamine (DA) into
      the lateral brain ventricle by method used before in our laboratory. The
      amplitude of the first deep negative (N(1)) peak significantly increased to 109
      114% after both doses of DA in the control group and to 138-139% in mercury
      treated animals. The amplitude of the next positive (P(1)) wave decreased to 94%
      and 86% in the control group after 50 and 100 nmols of DA, respectively. In Hg
      treated group after 50 nmols of DA, the value dropped down to 91%, but increased
      to 109% after 100 nmols of DA. The increasing of DeltaN(1)P(1) was observed in
      the control group to 112% after 50 nmols and to 109% after 100 nmols of DA and in
      Hg-exposed rats, respectively, to 127% and to 129%. The described changes were
      statistically significant (p < 0.05). The N(1) and P(1) latencies were prolonged
      in the control group after both doses of DA. In Hg-treated group, the
      prolongation of N(1) latency was recorded, while the P(1) latency was not
      changed. We concluded that prenatal Hg intoxication disturbed the effect of DA on
      FVEP.

PMID- 15520496
TI  - Effect of different forms of vasoactive intestinal peptide on cAMP formation in
      the mammalian cerebral cortex.
AB  - Chicken, guinea pig and mammalian (human/porcine/rat) vasoactive intestinal
      peptides (VIP; 0.001-3 microM) were compared with respect to their ability to
      stimulate adenosine 3', 5'-cyclic monophosphate (cAMP) formation in the cerebral
      cortical slices of rat and guinea pig. Of the tested peptides, i.e. chicken VIP
      (cVIP), guinea pig VIP (gpVIP) and human/rat/porcine (mammalian) VIP (mVIP), the
      strongest stimulator of cAMP synthesis was cVIP, and the weakest one - the gpVIP.
      Pituitary adenylate cyclase-activating polypeptide (PACAP) used as a reference
      drug at 0.1 microM concentration strongly stimulated cAMP formation in the
      cerebrum of both species, being, however, significantly more potent in the guinea
      pig model. The obtained data demonstrate significant differences in biological
      activity between cVIP and two distinct mammalian VIPs in the cerebral cortex of
      rat and guinea pig.

PMID- 15520497
TI  - Preparation of cardiovascular disease-related genes microarray and its
      application in exploring ligustrazine-induced changes in endothelial gene
      expression.
AB  - To study the molecular mechanism of action of ligustrazine, a low-density
      oligonucleotide microarray for cardiovascular disease-related genes, was
      constructed, and the preparation and hybridization protocols were optimized.
      Under the optimized conditions, the molecular mechanism of action of ligustrazine
      was analyzed with human umbilical vein endothelial cells. After 4 h of treatment
      with 100 microg/ml of ligustrazine, calcium-ATPase gene, sodium channel gene,
      P450c11 gene in human umbilical vein endothelial cells were up-regulated while
      apolipoprotein C-III gene was down-regulated. The results were shown to be
      reproducible. RT-PCR confirmed the results from microarray. These results suggest
      that ligustrazine may act on the function of human umbilical vein endothelial
      cells via modulating the expressions of cardiovascular disease-related genes.
      This also demonstrates the use of oligonucleotide microarray technology as an
      approach to studying targets of active components of Traditional Chinese
      Medicine.

PMID- 15520498
TI  - Epirubicin HCl toxicity in human-liver derived hepatoma G2 cells.
AB  - Epirubicin HCl is a new anthracycline analog and derivative of doxorubicin.
      Doxorubicin is a potent anticancer agent, the use of which is limited by its
      cumulative dose-dependent cardiotoxicity. Epirubicin HCl has more favorable
      therapeutic index than doxorubicin and possesses less hematologic and cardiac
      toxicity at comparable doses. Hepatoma G2 cells are a valuable model to study
      hepatocellular carcinoma and the liver, where drugs are metabolized. The goal of
      our study was to evaluate the cytotoxic effect of epirubicin HCl on viability of
      Hep G2 cells measured using the MTT cytotoxicity test. Epirubicin HCl produced a
      concentration- and time-dependent cytotoxicity to Hep G2 cells. The mechanism of
      cytotoxicity of epirubicin HCl (IC(50) value of 1.6 mug/ml within 24 h) appeared
      to involve a production of free radical species since activities of free radical
      scavenging enzymes (SOD, catalase, Se-dependent GPx) were increased. Addition of
      SOD prevented cytotoxicity of epirubicin HCl, and also counteracted the
      apoptosis. DNA fragmentation was determined to evaluate apoptosis. Western blot
      analysis indicated a decrease in GST-pi expression and increased activity of
      NADPH-dependent cytochrome P450 reductase which is a major enzyme in the
      conversion of epirubicin HCl to a free radical. It is proposed that production of
      reactive oxygen species increased by the treatment with epirubicin HCl can cause
      lipid peroxidation, which subsequently promotes apoptosis and reduces cell
      viability. Superoxide dismutase, catalase and glutathione peroxidase must be
      considered as a part of the intracellular antioxidant defense mechanism of Hep G2
      cells against single electron reducing quinone-containing anticancer antibiotics.

PMID- 15520499
TI  - Acetylator phenotyping in patients with malignant lymphomas, using caffeine as
      the metabolic probe.
AB  - OBJECTIVE: The study was designed to answer the question whether a particular
      (slow/fast) acetylator phenotype is a risk for malignant lymphoma patients.
      Differences in acetylator phenotypes were previously described in urinary bladder
      and colorectal carcinoma patients compared to controls. Addressing this issue may
      help understanding the possible role of xenobiotics' metabolism in the
      pathogenesis of malignant lymphomas. Caffeine is currently preferred as a
      metabolic probe due to its noninvasiveness. DESIGN: Case-control study. SETTING:
      Hematology/oncology inpatient unit and outpatient clinic, Ain Shams University
      Hospitals, Cairo, Egypt: a tertiary care academic medical institution.
      PARTICIPANTS: Urine samples were collected 4 h after the oral administration of a
      caffeine-containing beverage to 83 patients with malignant lymphomas and 92
      control subjects. Diagnosis of lymphoma was ascertained histopathologically.
      Controls were matched in terms of age, sex and residence (urban/rural).
      MEASUREMENTS: To define the acetylation phenotype, the nanomolar ratio of the
      urinary concentrations of the caffeine metabolites: acetylamino-6-amino-3
      methyluracil and 1-methylxanthine (AAMU/1X) was calculated for every study
      subject. RESULTS: An excess of fast acetylators was shown in the malignant
      lymphoma group compared to the control. The odds ratio for malignant lymphoma
      associated with fast acetylation was 1.304 (95% CI, 0.709-2.398; p = 0.439).
      Paradoxically, an excess of the slow acetylator phenotype was observed in
      patients with low-grade non-Hodgkin lymphoma (n = 25) compared to other subjects
      of the lymphoma group. The odds ratio for low-grade lymphoma associated with slow
      acetylation was 4.00 (95% CI, 1.316-12.155; p = 0.014). CONCLUSIONS: Owing to the
      small sample size, the association between the acetylator phenotype and malignant
      lymphomas could not be excluded. However, the study suggests that, compared to
      other types of lymphoma, low-grade non-Hodgkin lymphoma would be associated with
      slow acetylator phenotype.

PMID- 15520500
TI  - Effects of enoxaparin on histomorphometric parameters of bones in rats.
AB  - Enoxaparin sodium is a low-molecular-weight heparin. It is not clear whether the
      risk of development of osteoporosis after administration of low-molecular-weight
      heparins is lower than after administration of standard heparin. The aim of the
      present study was to investigate the effects of enoxaparin on histomorphometric
      parameters of bones in female Wistar rats (13-15 weeks old at the beginning of
      the experiment). Enoxaparin was administered at doses of 1000 anti-Xa IU/kg sc
      daily or 2000 anti-Xa IU/kg sc daily for 4 weeks. Bone mass, mineral and calcium
      content (in the tibia, femur and L-4 vertebra), length and diameter in the tibia
      and femur, and histomorphometric parameters of the tibia (periosteal and
      endosteal transverse growth, width of periosteal and endosteal osteoid, area of
      the transverse cross-section of the cortical bone in the diaphysis and area of
      the transverse cross-section of the marrow cavity) and the femur (width of
      epiphyseal and metaphyseal trabeculae, width of epiphyseal cartilage) were
      examined. Enoxaparin, administered at doses of 1000 anti-Xa IU/kg sc daily or
      2000 anti-Xa IU/kg sc daily for 28 days, induced osteopenic changes in the rat
      skeletal system. The changes observed in bone histomorphometric parameters
      indicate that enoxaparin caused the inhibition of bone formation and
      intensification of bone resorption.

PMID- 15520501
TI  - SIB 1893, a selective mGluR5 receptor antagonist, potentiates the anticonvulsant
      activity of oxcarbazepine against amygdala-kindled convulsions in rats.
AB  - SIB 1893 (a non-competitive antagonist of group I metabotropic glutamate
      receptors), given at 40 mg/kg (but not at 20-30 mg/kg), shortened the
      afterdischarge duration in amygdala-kindled rats, being ineffective on other
      seizure parameters - seizure severity, seizure duration, and afterdischarge
      threshold. Oxcarbazepine (at 7.5 mg/kg, but not at 5 mg/kg), a newer
      antiepileptic drug, reduced seizure severity, seizure and afterdischarge
      durations. When combined at ineffective doses in amygdala kindling, SIB 1893 at
      20 or 30 mg/kg and oxcarbazepine at 5 mg/kg, significantly reduced seizure and
      afterdischarge durations. The results indicate that combinations of oxcarbazepine
      with antagonists of group I metabotropic glutamate receptors may offer a novel
      therapeutic approach in cases of drug-resistant epilepsy.

PMID- 15520502
TI  - Effect of single and repeated in vitro exposure of ovarian follicles to o,p'-DDT
      and p,p'-DDT and their metabolites.
AB  - The aim of the presented study was to compare the effect of o,p'-DDT [1,1
      dichloro-2,2-bis-(p,p'-chlorophenyl)-ethylene] and p,p'-DDT [1,1,1-trichloro-2,2
      bis-(p-chlorophenyl)-ethane] and their metabolites DDE and DDD on estradiol
      secretion by ovarian follicles, the target organs of environmental estrogens.
      Theca interna (Tc) and granulosa cells (Gc) were collected from medium size
      porcine follicles and cultured as a monolayer. The cells were initially cultured
      for 24 h to allow attachment to the plates and then media were changed for the
      new ones and o,p'-DDT and p,p'-DDT and their metabolites: o,p'-DDE, p,p'-DDE and
      o,p'-DDD were added at doses of 4, 40, 400 ng and 4 microg/ml medium to
      investigate dose-dependent effects. Media were collected after 24 h and frozen
      for estradiol content determination. When the effect of single and repeated
      exposure was investigated, the lowest dose of 4 ng/ml and the highest one of 4
      microg/ml were chosen on the basis of the results of Experiment 1. o,p'-DDT
      exerted antiestrogenic action at all doses used while its metabolites and p,p'
      DDT and its metabolites decreased estradiol secretion only when present in the
      medium at a dose of 4 ng/ml. The highest doses caused the increase in estradiol
      secretion. Parent o,p'-DDT and its metabolites showed antiestrogenic action after
      single exposure to 4 ng/ml while parent p,p'-DDT and its metabolites caused
      estrogenic action. All investigated compounds, except o,p'-DDT, increased
      estradiol secretion after single exposure to the dose of 4 microg/ml. Repeated
      exposure resulted in a massive antiestrogenic action of all investigated
      chemicals. In conclusion, our study points to time-dependent effect of DDT and
      its metabolites on ovarian follicles with the strongest estrogenic properties
      observed after single exposure and antiestrogenic action caused by repeated
      exposure. Given the duration of folliculogenesis, one can imagine many different
      potential mechanisms by which DDT could influence steroidogenesis.

PMID- 15520503
TI  - Cytotoxic and proapoptotic effects of new Pd(II) and Pt(II)-complexes with 3
      ethanimidoyl-2-methoxy-2H-1,2-benzoxaphosphinin-4-ol-2-oxide.
AB  - The new palladium (II) and platinum (II) complexes 2 and 3 with 3-ethanimidoyl-2
      methoxy-2H-1,2-benzoxaphospinin-4-ol-2-oxide 1 were synthesized and their
      physicochemical and pharmacological properties were determined. The cytotoxic
      effects of these complexes were examined on the two human leukemia cell lines, HL
      60 and NALM-6. Pd-complex 2 and Pt-complex 3 exerted significant cytotoxic
      activity. The effects exhibited by these two complexes were comparable to those
      reported for cis-platin and carboplatin. On the other hand, ligand 1 was not
      cytotoxic. As determined by caspase-3 activity assay, compounds 2 and 3 differed
      slightly in their mode of induction of the programmed cell death.

PMID- 15520504
TI  - Pharmacokinetic interaction after joint administration of zinc and imipramine in
      forced swim test in mice.
AB  - Recent preclinical and clinical data indicate beneficial role of zinc in the
      antidepressant treatment. To evaluate the mechanism of interaction between zinc
      and antidepressants, in the present study we examined the brain zinc, imipramine
      and desipramine concentrations in mice treated with combinations of zinc and
      imipramine and subjected to the forced swim test. We have chosen doses of zinc
      (10 mg/kg) and imipramine (15 mg/kg) which we have previously found to be
      ineffective in the forced swim test when given alone. However, when administered
      jointly, a significant reduction in the immobility time in this test was
      demonstrated. In the present study, we demonstrated a significant ca. 60%
      reduction in the brain desipramine and non-significant reduction (ca. 40%) in
      brain imipramine concentrations in the group of animals treated with zinc plus
      imipramine compared with animals treated with imipramine alone. The brain zinc
      concentration in the zinc plus imipramine group was reduced when compared with
      the group treated with zinc or imipramine alone. Since there was no increase in
      brain imipramine/desipramine or zinc brain concentration after combined zinc and
      imipramine treatment, the data suggest that pharmacodynamic rather than
      pharmacokinetic interaction between zinc and imipramine is responsible for
      behavioral effect in the forced swim test.

PMID- 15520505
TI  - Influence of lovastatin on BCL-2 and BAX expression by plasma cells and T
      lymphocytes in short-term cultures of multiple myeloma bone marrow mononuclear
      cells.
AB  - Lovastatin (LOV), until now largely used for the treatment of
      hypercholesterolemia is a new promising drug in multiple myeloma (MM), however,
      the precise mechanism of its antitumor activity is not clear yet. It is probable
      that this effect is mediated by down-regulation of BCL-2 expression. In this
      study, we analyzed BCL-2 and BAX expression in cells of MM patients exposed to
      LOV in short-term culture. The obtained results indicate an increase in
      susceptibility to apoptosis both in CD138+ malignant cells and CD8+ T
      lymphocytes. Interestingly, such a tendency was confirmed in vivo in MM patient
      subjected to 3 cycles of LOV therapy.

PMID- 15520506
TI  - Doxepin inhibits CYP2D6 activity in vivo.
AB  - OBJECTIVE: Doxepin is a tricyclic antidepressant formulated as a mixture of E
      (trans) and Z-(cis) stereoisomers. Cytochrome P450 2D6 (CYP2D6) catalyzes the
      hydroxylation of E-doxepin and E-N-desmethyldoxepin stereospecically. There is
      evidence that tricyclic antidepressants might inhibit CYP2D6 activity but there
      is no data about the influence of doxepin on CYP2D6. MATERIALS AND METHODS:
      Eleven patients diagnosed with depression according to ICD-10 criteria were
      included in the study. After wash-out period, before doxepin treatment, sparteine
      metabolic ratio (MR1) was assessed. After 2-weeks of doxepin treatment, MR2 was
      estimated. Sparteine and its metabolites were determined in urine by gas
      chromatographic method of Eichelbaum et al. RESULTS: Based on MR1 values, 10
      patients were classified as EM (extensive metabolizers) and 1 patient as PM (poor
      metabolizer). During the study, after doxepin treatment, none of patients has
      changed phenotype status. However, MR2 values were statistically significantly
      higher than MR1. CONCLUSION: These results show the inhibitory effect of doxepin
      on CYP2D6 activity and may be of clinical value, especially in polymedicated
      patients treated with other CYP2D6 substrates or inhibitors.

PMID- 15520511
TI  - Enzyme inhibiting lignans from Vitex negundo.
AB  - Two new lignans trivially named negundins A (1) and B (2), were isolated along
      with (+)-diasyringaresinol (3), (+)-lyoniresinol (4), vitrofolal E (5) and
      vitrofolal F (6), reported for the first time from this species. The structures
      of the new compounds were established through spectral studies. Compound 2 showed
      potent inhibitory activity against lipoxygenase enzyme, while 5 showed moderate
      activity against butyryl-cholinesterase.

PMID- 15520512
TI  - Cholinesterase inhibiting withanolides from Withania somnifera.
AB  - A total of two new (1, 2) and four known (3-6) withanolides were isolated from
      the whole plant of Withania somnifera. Their structures were elucidated on the
      basis of spectroscopic techniques and were characterized as 6alpha,7alpha-epoxy
      3beta,5alpha,20beta-trihydroxy-1-oxowitha-24-enolide (1), 5beta,6beta-epoxy
      4beta,17alpha,27-trihydroxy-1-oxowitha-2,24-dienolide (2), withaferin-A (3), 2,3
      dihydrowithaferin-A (4), 6alpha,7alpha-epoxy-5alpha,20beta-dihydroxy-1-oxowitha
      2,24-dienolide (5), and 5beta,6beta-epoxy-4beta-hydroxy-1-oxowitha-2,14,24
      trienolide (6), respectively. Compounds 2, 3, 5, and 6 displayed inhibitory
      potential against butyrylcholinesterase, but only compounds 3, 4, and 6 were
      found to be active against acetylcholinesterase.

PMID- 15520513
TI  - Functional analysis of genes implicated in Down syndrome: 1. Cognitive abilities
      in mice transpolygenic for Down Syndrome Chromosomal Region-1 (DCR-1).
AB  - Down syndrome occurs every 1/1000 births and is the most frequent genetic cause
      of mental retardation. The genetic substrate of Down syndrome, an extra
      chromosome 21, was discovered by Lejeune, half-a-century ago, and the chromosome
      has been fully sequenced, although the gene(s) implicated in the mental
      retardation observed with the syndrome are still unknown. Observations of
      patients with partial trisomy of the 21q22.2 fragment suggest that most of the
      signs of the syndrome, including mental retardation, could be influenced by the
      region referred to as the Down Minimal Chromosomal Region-1 (DCR-1) for that
      reason. Using the extensive syntenies between human chromosome 21 and murine
      chromosome 16, Smith et al. (1995, 1997) developed transpolygenic mice with human
      chromosome 21 fragments covering the DCR-1. Here, we explored cognitive
      performances in mice over-expressing the genes carried by these fragments with
      the Morris water-maze and fear-conditioning procedures. The 152F7 transpolygenic
      mice had lower performance levels, compared to non-transgenic and other
      transgenic mice on most measurements in the water-maze. In fear-conditioning, all
      transgenic mice recorded lower performance levels compared to controls in the
      altered context stage. The 230E8, 141G6 and 285E6 mice failed to learn or react
      when the sound used as the conditional stimulus was added. These results showed
      that the 152F7 region played a crucial role in cognitive impairment, supporting
      the hypothesis of DYRK-1A gene involvement. However, the data presented here also
      suggest that other chromosomal regions within the DCR-1 may be involved in
      specific cognitive functions.

PMID- 15520514
TI  - A study of genetic and environmental influences on maternal and paternal CBCL
      syndrome scores in a large sample of 3-year-old Dutch twins.
AB  - BACKGROUND: There is increasing evidence that behavioral problems are common in
      very young children, yet little is known about the etiology of individual
      differences in these problems. It is unclear to what degree environmental and
      genetic factors influence the development of early child psychopathology. In this
      paper, we focus on the following issues. Firstly, to what degree do genetic and
      environmental factors influence variation in behavioral problems? Secondly, to
      what degree are these underlying etiological factors moderated by sex and
      informant? We investigate these issues by analyzing Child Behavior Checklist
      (CBCL) data on 9689 3-year-old twin pairs. METHODS: Rater Bias and Psychometric
      Models were fitted to CBCL/2-3 data obtained from mothers and fathers to
      determine the genetic and environmental contributions to the five CBCL
      syndromes:aggressive, oppositional, overactive, withdrawn, and anxious/depressed
      behavior. RESULTS: Parental ratings are influenced by aspects of the child's
      behavior that are experienced in the same way by both parents and by aspects of
      the child's behavior that are experienced uniquely by each parent. There is
      evidence for high genetic contributions to all CBCL syndromes. Shared and non
      shared environmental influences play significant roles as well. One exception is
      overactive behavior, which is influenced by genetic and non-shared environmental
      influences only. CONCLUSIONS: Variation in behavior problems in the very young
      shows high heritability. Individual raters offer unique perspectives that can
      have an impact on estimates of problem behavior and genetic architecture.
      Therefore, multi-informant approaches in the assessment of the very young will be
      useful to clinicians and researchers alike.

PMID- 15520515
TI  - Genetic influences on CHD-death and the impact of known risk factors: comparison
      of two frailty models.
AB  - The importance of some recognized risk factors on genetic influences for coronary
      heart disease (CHD) needs further clarification. The aim of the present study was
      therefore to study the impact of known risk factors on genetic influences for CHD
      death. Both twin (correlated gamma-frailty) and non-twin models (univariate gamma
      frailty) were utilized and compared regarding their suitability for genetic
      analyses. The study population consisted of twins born in Sweden between 1886 and
      1925. As expected, our findings indicate that genetic influences are important
      for CHD-death. Inclusion of risk factors in the twin-model increased heritability
      estimates, primarily due to a substantial reduction in non-shared environmental
      variances. The genetic influences for CHD-death are only marginally mediated
      through the risk factors among males, but more so among females. Although the
      outcome phenotype used in the present study is not behavioral, the analyses
      demonstrate the potential of frailty models for quantitative genetic analyses of
      categorical phenotypes.

PMID- 15520516
TI  - An empirical comparison of information-theoretic selection criteria for
      multivariate behavior genetic models.
AB  - Information theory provides an attractive basis for statistical inference and
      model selection. However, little is known about the relative performance of
      different information-theoretic criteria in covariance structure modeling,
      especially in behavioral genetic contexts. To explore these issues, information
      theoretic fit criteria were compared with regard to their ability to discriminate
      between multivariate behavioral genetic models under various model, distribution,
      and sample size conditions. Results indicate that performance depends on sample
      size, model complexity, and distributional specification. The Bayesian
      Information Criterion (BIC) is more robust to distributional misspecification
      than Akaike's Information Criterion (AIC) under certain conditions, and
      outperforms AIC in larger samples and when comparing more complex models. An
      approximation to the Minimum Description Length (MDL; Rissanen, J. (1996). IEEE
      Transactions on Information Theory 42:40-47, Rissanen, J. (2001). IEEE
      Transactions on Information Theory 47:1712-1717) criterion, involving the
      empirical Fisher information matrix, exhibits variable patterns of performance
      due to the complexity of estimating Fisher information matrices. Results indicate
      that a relatively new information-theoretic criterion, Draper's Information
      Criterion (DIC; Draper, 1995), which shares features of the Bayesian and MDL
      criteria, performs similarly to or better than BIC. Results emphasize the
      importance of further research into theory and computation of information
      theoretic criteria.

PMID- 15520517
TI  - A genetic analysis of avian personality traits: correlated, response to
      artificial selection.
AB  - Individuals in a range of species consistently differ in their behavior towards
      mild challenges, over age and time. Differences have been found for several
      personality traits in a range of species. In great tits these traits have a
      genetic basis and are phenotypically correlated. Estimates of genetic
      correlations are, however, fundamental to understanding the evolution of
      consistent individual differences in behavior. This study analyzed two selection
      experiments on two avian personality traits, early exploratory behavior and risk
      taking behavior. The selection lines used were both started using wild great tits
      (Parus major) from two natural populations. Genetic correlations were calculated
      using the response and the correlated response to artificial selection. We found
      genetic correlations ranging from 0.51 to 0.66, based on individual values, and
      from 0.84 to 1.00 based on nest means. Genetic correlations can be due to
      pleiotropic effects or to linkage disequilibrium. The different behavioral traits
      might therefore have a common genetic basis, possibly constraining independent
      evolution of personality traits in natural populations. These results are
      discussed in relation to domain generality and domain specificity of
      personalities.

PMID- 15520518
TI  - Behavioral characterization of wild derived male mice (Mus musculus musculus) of
      the PWD/Ph inbred strain: high exploration compared to C57BL/6J.
AB  - PWD/Ph is an inbred mouse strain derived from wild mice trapped in central Czech
      Republic. These mice are of the Mus musculus musculus subspecies, whose ancestors
      separated from those of Mus musculus domesticus about one million years ago.
      There is a high degree of variation in the genomic sequence and a wide range of
      phenotypes between PWD/Ph and standard laboratory inbred mouse strains, the
      genomes of which are principally Mus musculus domesticus in origin, making PWD/Ph
      mice an useful resource for complex trait research. As a first step in taking
      advantage of this resource, a preliminary characterization of the behavior of
      PWD/Ph mice was performed. Groups of 10 PWD/Ph and C57BL/6J male mice were tested
      in the open field, novel object exploration task and Morris water maze. PWD/Ph
      were marginally more anxious than C57BL/6J mice in the open field but
      subsequently displayed much higher levels of exploration and lower anxiety than
      C57BL/6J mice following introduction of a novel object. As C57BL/6J itself is
      rated as highly explorative among classical inbred strains, PWD/Ph probably
      represents an extreme among mouse strains for this specific behavior. PWD/Ph and
      C57BL/6J mice differed in their water escape training profiles in the Morris
      water maze, perhaps reflecting different motivational factors. However, there
      were no differences in overall cognitive ability (spatial learning) as both
      groups learned to find the hidden platform and performed equally well when the
      location of the platform was changed. This is the first quantification of the
      behavior of PWD/Ph mice and the results are promising for the potential of the
      consomic panel currently being generated with PWD/Ph and C57BL/6J as a tool for
      the molecular dissection of behavior.

PMID- 15520525
TI  - Reorganization of nuclear compartments of type A neurons of trigeminal ganglia in
      response to inflammatory injury of peripheral nerve endings.
AB  - In this study we have taken advantage of the high nuclear responsiveness of type
      A sensory ganglia neurons to variations of cellular activity to investigate the
      reorganization and dynamics of nuclear compartments involved in transcription and
      RNA processing in response to neuronal injury. As experimental model we have used
      the inflammatory injury of the peripheral nerve endings induced by formalin
      injection in the areas of ophthalmic/maxillary nerve distribution. We have
      performed immunofluorescence and confocal laser microscopy analysis with specific
      antibodies for different nuclear compartments and ultrastructural analysis. The
      initial response to neuronal injury, within the 3 days post-injury, consisted of
      chromatin condensation, reduction in the expression level of acetylated histone
      H4, accumulation of perichromatin granules, reorganization of splicing factors in
      prominent nuclear speckles, reduction in the number of Cajal bodies and nucleolar
      alterations. These changes tended to revert by day 7 post-injury and are
      consistent with a transient inhibition of transcription and RNA processing.
      Moreover, we have observed an early and sustained expression of the transcription
      factor c-Jun. These results illustrate the transcription-dependent organization
      of nuclear compartments in type A trigeminal neurons and also support the
      importance of the nuclear response to axonal injury as a key component in the
      regenerative capacity of this neuronal population.

PMID- 15520526
TI  - Cellular and subcellular localization of heme oxygenase-2 in monkey retina.
AB  - Carbon monoxide (CO), an activator of soluble guanylate cyclase (SGC) and
      generated enzymatically by heme oxygenases (HO), is considered to function as an
      intra- and intercellular neuromodulator or neurotransmitter in the central and
      peripheral nervous systems. HO-2 is the constitutive isoform of HO and is more
      prevalent in nervous tissues than in the other peripheral tissues. Because
      previous studies have demonstrated different distributions of HO-2 in the retina
      depending on the species of animals, the aim of this study was to identify which
      cell types of the monkey retina express HO-2. The expression of HO-2 protein was
      examined in monkey retina by Western blot analysis. Immunoblottings from monkey
      homogenates revealed a single clear protein band with a molecular mass of 36 kDa
      that is corresponding to rat HO-2. Immunoreactivity of HO-2 was found in the
      perikarya of ganglion cells. Density of immunoreactive ganglion cells was higher
      in the central area of retina than in the peripheral retina, and somata of larger
      ganglion cells were stained more densely than smaller ones. In electron
      microscopy, immunoreactivity of HO-2 was localized on the membrane of the
      endoplasmic reticulum and the nuclear outer membrane of the ganglion cells. By
      contrast, inner plexiform layer, inner nuclear layer and outer nuclear layer were
      devoid of HO-2 immunoreactivity. cGMP were strongly localized in all of ganglion
      cells. Some cells contributed to the relatively faint cGMP staining were seen in
      the inner nuclear layer. In combination of HO-2 and cGMP immunocytochemistry, the
      overlap of co-localization of HO-2 and cGMP would suggest that HO-2 in the
      ganglion cells would serve as a source for CO generation and CO could serve as a
      gaseous signaling molecule modulator of neural activity in the retina of monkey.

PMID- 15520527
TI  - Accumulation of sulfatide in neuronal and glial cells of arylsulfatase A
      deficient mice.
AB  - Arylsulfatase A (ASA) degrades sulfatide, seminolipid and lactosylceramide
      sulfate, glycolipids recognized by the Sulph I antibody although sulfatide is
      considered the main antigen. Sulfatide is myelin associated but studies have
      shown a minor distribution also in non-myelin forming cells. The aim of this work
      was to further study sulfatide in neurons and astrocytes by immunohistochemistry,
      facilitated by investigation of tissue from adult ASA deficient (ASA -/-) mice.
      Cells with a low presence of sulfatide might be detected due to lack of ASA
      activity and accumulation of Sulph I antigens. Sulfatide positive astrocytes and
      neurons were more numerous and intensely stained in ASA -/- mice, demonstrating a
      sulfatide accumulation compared to controls. Sulph I staining was especially
      increased in the molecular layer of cerebellum, in which Purkinje cell dendrites
      displayed an altered morphology, and in layer IV-VI of cerebral cortex. In
      hippocampus, immunostaining was found in neuronal cytoplasm in ASA -/- but in
      nuclear membranes of control mice. We observed a gray matter astrogliosis, which
      appeared to be associated to sulfatide accumulation. In addition, the
      developmental change (<20 months) of Sulph I antigens, galactosylceramide,
      phospholipids and cholesterol were followed by lipid analyses which verified
      sulfatide and seminolipid accumulation in adult ASA -/- mice, although no
      lactosylceramide sulfate could be detected. In addition to demonstrating
      sulfatide in neurons and astrocytes, this study supports the value of ASA -/-
      mice as a model for metachromatic leukodystrophy and suggests that accumulation
      of sulfatide beyond myelin might contribute to the pathology of this disease.

PMID- 15520528
TI  - Chemoarchitectonic heterogeneities in the primate zona incerta: clinical and
      functional implications.
AB  - In view of the recent focus on the zona incerta (and surrounding regions) as a
      target for deep brain stimulation in patients with Parkinson Disease, we have
      explored incertal cyto and chemoarchitecture in normal and MPTP (methyl-4-phenyl
      1,2,3,6-tetrahydropyridine)-treated macaque monkeys. Brains were processed for
      routine tyrosine hydroxylase (TH), nitric oxide synthase (NOs), parvalbumin (Pv)
      and calbindin D 28k (Cal) immunocytochemistry, as well as for Nissl staining. We
      show four main sectors in the zona incerta, namely rostral, dorsal, ventral and
      caudal, each with a largely distinct cytoarchitecture. Each of the antibodies
      screened had signature distribution patterns across the zona incerta; TH+ cells
      were localised within the rostral sector, NOs+ cells were concentrated in the
      dorsal sector, Pv+ cells were found mainly in the ventral sector and Cal+ cells
      were distributed uniformly across all sectors. These patterns match closely those
      reported in non primates. We found no major differences in the distribution and
      shape of labelled cells in the zona incerta of MPTP-treated monkeys when compared
      to control. In conclusion, we report that the primate zona incerta shows
      considerable cyto and chemoarchitectonic heterogeneity; that it forms a nucleus
      with distinct sectors presumably associated with diverse functions--from
      generating arousal to shifting attention, and from controlling visceral activity
      to influencing posture and locomotion. These functions have been proposed for the
      zona incerta of non primates. Our results have clinical implications, in that
      deep brain stimulation of the zona incerta (or parts thereof) could manifest in
      signs and symptoms other than those associated with the motor system. Such
      clinical stimulations could well involve other systems, including those of
      arousal, attention and visceral control.

PMID- 15520529
TI  - Localization of vanilloid receptor 1 (TRPV1/VR1)-like immunoreactivity in
      goldfish and zebrafish retinas: restriction to photoreceptor synaptic ribbons.
AB  - The vanilloid receptor type 1 (TRPV1/VR1) is a non-specific calcium-permeable
      ionotropic cation channel expressed in the peripheral sensory system as well as
      in the central nervous system. An endogenous ligand for TRPV1 is arachidonoyl
      ethanolamide (anandamide), which also activates the metabotropic cannabinoid
      receptor 1 (CB1). Previous studies in this laboratory reported CB1 receptors and
      CB1-mediated effects on voltage-gated currents in goldfish cones and bipolar
      cells. In this study, we show TRPV1-like-immunoreactivity (TRPV1-L-IR) by
      immunoblot analysis of goldfish retina and rat brain homogenates with a guinea
      pig polyclonal antibody against the C-terminus of the rat TRPV1. Light-level
      immunocytochemistry showed restriction of the guinea pig-TRPV1 antibody to a very
      narrow band in the outer plexiform layer in goldfish and zebrafish retinas.
      However, no immunoreactivity was detected using rabbit-polyclonal antibodies
      against the C or N-termini of the rat TRPV1. Pre and post-embedding electron
      microscopy (EM) immunocytochemistry revealed that TRPV1-L-IR (using the guinea
      pig antibody) was restricted to synaptic ribbons of all cones and many rods, but
      never was observed at the synaptic ribbons of bipolar cells. While pre-embedded
      tissue showed diffuse label associated only with photoreceptor-synaptic ribbons,
      analysis of post-embedded tissue showed label tightly restricted to synaptic
      ribbons of all cones and many rods. Oblique sections showed that immunogold
      particles were confined to the outer electron dense region of the ribbons, with
      few or no gold particles in the ribbon core or associated with tethers or
      vesicles. Although TRPV1-L-IR described here, does not necessarily represent
      TRPV1 antigen associated with synaptic ribbons, these data provide an unequivocal
      label with which to study the functional dynamics of ribbon formation and
      degradation in teleost photoreceptors.

PMID- 15520530
TI  - The effects of nerve growth factor upon the neuropeptide content of the
      suprachiasmatic nucleus of rats withdrawn from ethanol are mediated by the
      nucleus basalis magnocellularis.
AB  - It has been previously shown that withdrawal from alcohol decreases the synthesis
      and expression of vasopressin (VP) and vasoactive intestinal polypeptide (VIP) in
      the suprachiasmatic nucleus (SCN), and that the infusion of NGF over 1 month
      completely restores these changes. Because SCN neurons do not express TrkA, NGF
      might have exerted its effects either through direct signalling of the neurons
      via p75NTR or by enhancing the activity of the cholinergic afferents to the SCN,
      which arise from the nucleus basalis magnocellularis (NBM). The observation that
      the infusion of NT-3 to withdrawn rats does not elicit any change in neuropeptide
      expression in the SCN suggests that ACh might be implicated in this process, a
      hypothesis that we have attempted to clarify in this study. For this purpose we
      destroyed, with quinolinic acid, the NBM of rats withdrawn from ethanol and later
      infused them with NGF over a period of 13 days. The total number and the somatic
      volume of SCN neurons immunoreactive for VP and VIP were stereologically
      estimated. No differences were found in the total number of neurons between
      quinolinic-injected NGF-treated withdrawn animals and intact withdrawn rats.
      However, the somatic volume of SCN neurons from quinolinic-injected animals was
      significantly reduced relative to control and withdrawn rats. The present results
      unequivocally demonstrate that the trophic effects exerted by NGF upon SCN
      neurons do not depend on direct neuronal signalling. Instead, they are indirect
      and, according to our results, NBM neurons, whose axons give rise to a
      cholinergic projection to the SCN, seem to be essential for eliciting those
      effects.

PMID- 15520531
TI  - Neurite outgrowth from hippocampal neurons is promoted by choroid plexus
      ependymal cells in vitro.
AB  - Choroid plexus ependymal cells (CPECs) were known to promote axonal growth when
      choroid plexus is grafted into the adult rat spinal cord. The present study was
      carried out to examine whether CPECs promote axonal outgrowth from neurons
      derived from the CNS in vitro. Hippocampal neurons were cocultured on CPEC
      monolayers. After 24 h, neurite extension was evaluated using various parameters
      in comparison with cultures grown on poly-L-lysine (PLL)-coated plates and
      cocultures grown on astrocyte monolayers. The primary neurite length and total
      neurite length were longest in the cocultures with CPECs. The number of primary
      neurites and the number of branches were larger in the cultures with CPECs than
      in the cultures on PLL-coated plates, but almost the same as in the cocultures
      with astrocytes. Next, we examined whether the neurite extension-promoting effect
      occurring within 24 h is due primarily to contact with the CPECs or to factors
      secreted by CPECs into the culture medium. The CPEC monolayers were killed by
      ethanol fixation, and neurons cultured on them. The neurons extended long
      neurites with elaborate branching, as in the case of cocultures grown on living
      CPECs. On the other hand, CPEC-conditioned medium exhibited less promoting effect
      on neurite outgrowth from hippocampal neurons. These results indicate that CPECs
      have a capacity to promote neurite outgrowth from CNS neurons in vitro , and that
      surface plasma membrane-bound components of CPECs strongly contribute to the
      enhancement of neurite outgrowth in the present coculture system.

PMID- 15520532
TI  - Identification of a non-linear model as a new method to detect expiratory airflow
      limitation in mechanically ventilated patients.
AB  - Expiratory flow limitation (EFL) can occur in mechanically ventilated patients
      with chronic obstructive pulmonary disease and other disorders. It leads to
      dynamic hyperinflation with ensuing deleterious consequences. Detecting EFL is
      thus clinically relevant. Easily applicable methods however lack this detection
      being routinely made in intensive care. Using a simple mathematical model, we
      propose a new method to detect EFL that does not require any intervention or
      modification of the ongoing therapeutic. The model consists in a monoalveolar
      representation of the respiratory system, including a collapsible airway that is
      submitted to periodic changes in pressure at the airway opening: EFL provokes a
      sharp expiratory increase in the resistance Rc of the collapsible airway. The
      model parameters were identified via the Levenberg-Marquardt method by fitting
      simulated data on the airway pressure and the flow signals recorded in 10
      mechanically ventilated patients. A sensitivity study demonstrated that only 8/11
      parameters needed to be identified, the remaining three being given reasonable
      physiological values. Flow-volume curves built at different levels of positive
      expiratory pressure, PEEP, during "PEEP trials" (stepwise increases in positive
      end-expiratory pressure to optimize ventilator settings) have shown evidence of
      EFL in three cases. This was concordant with parameter identification (high Rc
      during expiration for EFL patients). We conclude from these preliminary results
      that our model is a potential tool for the non-invasive detection of EFL in
      mechanically ventilated patients.

PMID- 15520533
TI  - Mathematical modelling of an ischemic stroke: an integrative approach.
AB  - Understanding the mechanisms and the time and spatial evolution of penumbra
      following an ischemic stroke is crucially important for developing therapeutics
      aimed at preventing this area from evolving towards infarction. To help in
      integrating the available data, we decided to build a formal model. We first
      collected and categorised the major available evidence from animal models and
      human observations and summarized this knowledge in a flow-chart with the
      potential key components of an evolving stroke. Components were grouped in ten
      sub-models that could be modelled and tested independently: the sub-models of
      tissue reactions, ionic movements, oedema development, glutamate excitotoxicity,
      spreading depression, NO synthesis, inflammation, necrosis, apoptosis, and
      reperfusion. Then, we figured out markers, identified mediators and chose the
      level of complexity to model these sub-models. We first applied this integrative
      approach to build a model based on cytotoxic oedema development following a
      stroke. Although this model includes only three sub-models and would need to
      integrate more mechanisms in each of these sub-models, the characteristics and
      the time and spatial evolution of penumbra obtained by simulation are
      qualitatively and, to some extent, quantitatively consistent with those observed
      using medical imaging after a permanent occlusion or after an occlusion followed
      by a reperfusion.

PMID- 15520534
TI  - Multi-formalism modelling and simulation: application to cardiac modelling.
AB  - Cardiovascular modelling has been a major research subject for the last decade.
      Different cardiac models have been developed at a cellular level as well as at
      the whole organ level. Most of these models are defined by a comprehensive
      cellular modelling using continuous formalisms or by a tissue-level modelling
      often based on discrete formalisms. Nevertheless, both views still suffer from
      difficulties that reduce their clinical applications: the first approach requires
      heavy computational resources while the second one is not able to reproduce
      certain pathologies. This paper presents an original methodology trying to gather
      advantages from both approaches, by means of a hybrid model mixing discrete and
      continuous formalisms. This method has been applied to define a hybrid model of
      cardiac action potential propagation on a 2D grid of endocardial cells, combining
      cellular automata and a set of cells defined by the Beeler-Reuter model. For
      simulations under physiological and ischemic conditions, results show that the
      action potential propagation as well as electrogram reconstructions are
      consistent with clinical diagnosis. Finally, the advantage of the proposed
      approach is discussed within the frame of cardiac modelling and simulation.

PMID- 15520535
TI  - Automated medical diagnosis with fuzzy stochastic models: monitoring chronic
      diseases.
AB  - As the world population ages, the patients per physician ratio keeps on
      increasing. This is even more important in the domain of chronic pathologies
      where people are usually monitored for years and need regular consultations. To
      address this problem, we propose an automated system to monitor a patient
      population, detecting anomalies in instantaneous data and in their temporal
      evolution, so that it could alert physicians. By handling the population of
      healthy patients autonomously and by drawing the physicians' attention to the
      patients-at-risk, the system allows physicians to spend comparatively more time
      with patients who need their services. In such a system, the interaction between
      the patients, the diagnosis module, and the physicians is very important. We have
      based this system on a combination of stochastic models, fuzzy filters, and
      strong medical semantics. We particularly focused on a particular tele-medicine
      application: the Diatelic Project. Its objective is to monitor chronic kidney
      insufficient patients and to detect hydration troubles. During two years,
      physicians from the ALTIR have conducted a prospective randomized study of the
      system. This experiment clearly shows that the proposed system is really
      beneficial to the patients' health.

PMID- 15520536
TI  - A biophysical model of neuronal dendrites' integrative properties: relations to
      morphological data.
AB  - We used a biophysical model to probe the basic integrative properties of primate
      pallidal neurons in order to obtain a better understanding of Basal Ganglia
      physiology. The first results we present here deal mainly with the way dendritic
      morphology influences these properties. Neuronal morphology has been
      quantitatatively analyzed in 3D. Single fast excitatory synaptic inputs resulting
      in AMPA receptors activations have been simulated, without regenerative voltage
      dependent conductances. Dendrites of both pallidal segments (GPi and GPe) showed
      a strong dependence of the synaptic efficacy upon distance from soma, but even
      the most distal dendritic synaptic sites were able to substantially depolarize
      the cell body. The mean synaptic efficacy was the same in both populations, but
      the attenuation of propagated post-synaptic potentials was higher in GPi neurons.
      All these features were very dependent on the dendritic diameters which appear to
      constitute a key parameter in these neuronal populations both with respect to the
      integration of afferent information and to the differences between cells in
      performing this task.

PMID- 15520537
TI  - Transmission of mechanical stresses within the cytoskeleton of adherent cells: a
      theoretical analysis based on a multi-component cell model.
AB  - How environmental mechanical forces affect cellular functions is a central
      problem in cell biology. Theoretical models of cellular biomechanics provide
      relevant tools for understanding how the contributions of deformable
      intracellular components and specific adhesion conditions at the cell interface
      are integrated for determining the overall balance of mechanical forces within
      the cell. We investigate here the spatial distributions of intracellular stresses
      when adherent cells are probed by magnetic twisting cytometry. The influence of
      the cell nucleus stiffness on the simulated nonlinear torque-bead rotation
      response is analyzed by considering a finite element multi-component cell model
      in which the cell and its nucleus are considered as different hyperelastic
      materials. We additionally take into account the mechanical properties of the
      basal cell cortex, which can be affected by the interaction of the basal cell
      membrane with the extracellular substrate. In agreement with data obtained on
      epithelial cells, the simulated behaviour of the cell model relates the
      hyperelastic response observed at the entire cell scale to the distribution of
      stresses and strains within the nucleus and the cytoskeleton, up to cell adhesion
      areas. These results, which indicate how mechanical forces are transmitted at
      distant points through the cytoskeleton, are compared to recent data imaging the
      highly localized distribution of intracellular stresses.

PMID- 15520538
TI  - Model driven quantification of individual and collective cell migration.
AB  - While the control of cell migration by biochemical and biophysical factors is
      largely documented, a precise quantification of cell migration parameters in
      different experimental contexts is still questionable. Indeed, these
      phenomenological parameters can be evaluated from data obtained either at the
      cell population level or at the individual cell level. However, the range within
      which both characterizations of cell migration are equivalent remains unclear. We
      analyse here to which extent both sources of data could be integrated within a
      unified description of cell migration by considering the motility of the
      endothelial cell line EAhy926. Using time-lapse video-microscopy and associated
      analysis of digital image time series, we quantified EAhy926 random motility
      coefficient, migration speed and trajectory persistence time in two different
      migration assays: the in vitro wound healing assay, and the cell-populated
      agarose drop assay. In order to analyse the agreement between independent
      quantifications of cell motility based either on individual cell analysis or cell
      population dynamic analysis, a theoretical multi-agents cellular model was
      developed and discussed as a possible theoretical framework able to unify these
      multi-scale data. Model simulations especially reveal the potential bias induced
      by cell proliferation and cell-cell adhesion when cell migration parameters are
      estimated from the extensively used in vitro wound healing assay.

PMID- 15520539
TI  - Time-delay dynamics for contagious bovine pleuropneumonia.
AB  - Modelling of contagious disease usually employs compartmental SEIR-like models
      where the waiting times in respective compartments are exponentially distributed.
      In this paper, we are interested in investigating how the distributions of
      sojourn times in infective compartments affect the dynamics and persistence of
      the contagious bovine pleuropneumonia, a chronic respiratory disease of cattle.
      Two kinds of extreme distributions of the sojourn times are considered: a Dirac
      delta-function and truncated Gaussian function leading to a model with (non
      constant) delay and the classical exponential distribution that stands for a
      model without delay. Expressions of the basic reproductive numbers are derived
      and dynamical behaviours are discussed for the three models. It is found that the
      spreading of disease exhibits wave-like oscillations for the time-delay dynamics.
      In contrast, the disease appears to last longer when the spreading is described
      by the classical dynamics without delay. Subsequently, the time-delay dynamics
      turns out to be more appropriate for the description of an experimental epidemic
      of CBPP.

PMID- 15520540
TI  - Epigenesis and dynamic similarity in two regulatory networks in Pseudomonas
      aeruginosa.
AB  - Mucoidy and cytotoxicity arise from two independent modifications of the
      phenotype of the bacterium Pseudomonas aeruginosa that contribute to the
      mortality and morbidity of cystic fibrosis. We show that, even though the
      transcriptional regulatory networks controlling both processes are quite
      different from a molecular or mechanistic point of view, they may be identical
      from a dynamic point of view: epigenesis may in both cases be the cause of the
      acquisition of these new phenotypes. This was highlighted by the identity of
      formal graphs modelling these networks. A mathematical framework based on formal
      methods from computer science was defined and implemented with a software
      environment. It allows an easy and rigorous validation and certification of these
      models and of the experimental methods that can be proposed to falsify or
      validate the underlying hypothesis.

PMID- 15520541
TI  - Mathematical methods for inferring regulatory networks interactions: application
      to genetic regulation.
AB  - This paper deals with the problem of reconstruction of the intergenic interaction
      graph from the raw data of genetic co-expression coming with new technologies of
      bio-arrays (DMA-arrays, protein-arrays, etc.). These new imaging devices in
      general only give information about the asymptotical part (fixed configurations
      of co-expression or limit cycles of such configurations) of the dynamical
      evolution of the regulatory networks (genetic and/or proteic) underlying the
      functioning of living systems. Extracting the casual structure and interaction
      coefficients of a gene interaction network from the observed configurations is a
      complex problem. But if all the fixed configurations are supposedly observed and
      if they are factorizable into two or more subsets of values, then the interaction
      graph possesses as many connected components as the number of factors and the
      solution is obtained in polynomial time. This new result allows us for example to
      partly solve the topology of the genetic regulatory network ruling the flowering
      in Arabidopsis thaliana .

PMID- 15520542
TI  - The survival attractor in the sensory functions: the example of hearing.
AB  - High noise levels may have an adverse effect on the normal cochlea function and
      lead to significant hearing loss. Clinically, exposure to high intensity impulse
      noise produces a wide range of audiometric effects which may result in long term
      or even irreversible symptoms. Nevertheless, there is sometimes a spontaneous
      rebound recovery of the auditory function. This phenomenon was previously studied
      in the vision, another sensory function. It was called the visual survival
      attractor. In view of the importance that the sensory organs have for the brain,
      and in particular in its function of recognising and dealing with its
      environment, it was interesting to know whether this survival attractor concept
      already described for vision occurs more generally in all the sensory functions.
      With this in mind we present here the results of a new study, this time on
      hearing. This study was carried out on guinea pigs subjected to a pulsed acoustic
      trauma simulating the sound of a gun going off. Auditory function was explored
      using electrocochleography and two types of investigation were carried out. At
      first the change in hearing loss was studied in relation to frequencies varying
      between 2 and 24 kHz by calculating the difference, at each frequency, between
      the compound action potential thresholds measured before and then 20 mn, 24 h and
      7 days after the acoustic trauma. On the other hand, the change in compound
      action potential amplitude was determined by varying the stimulating sound level
      from the auditory threshold up to 90 dB. This change was also recorded at the
      same time intervals as the investigation of hearing loss. In both the analysis of
      changes to hearing loss and in the investigation of variations in compound action
      potential, the results of the electrocochleographic investigations after acoustic
      trauma confirm the presence of a butterfly catastrophe type reaction process,
      that is positive evidence of a hearing survival attractor.

PMID- 15520543
TI  - Morphogenetic processes: application to cambial growth dynamics.
AB  - Both the physiological and the pathological morphogenetic processes that we can
      meet in embryogenesis, neogenesis and degenerative dysgenesis present common
      features: they are ruled by three different kinds of mechanisms, one related to
      cell migration, the second to cell differentiation and the third to cell
      proliferation. We deal here with an application to the cambial growth which
      essentially involves the third type of mechanism. Woody plants produce secondary
      tissue (secondary xylem and phloem) from a meristematic tissue called vascular
      cambium, responsible for the radial growth of a tree. This paper focuses on the
      formation of secondary xylem, considered in two dimensions in a cross-section
      framework. A new discrete modelling approach is used, based on the cellular
      scale, in order to attain a more accurate understanding of how the elementary
      microscopic behaviour of each cell takes part in the macroscopic morphogenesis.
      The mathematical model essentially uses an occurrence method simulating the main
      features of radial growth with simple geometric rules, such as Thom's division
      rule (Thom,1972)to account for the cell proliferation. The study applies to
      concrete instances in which the changes made in the geometrical cellular patterns
      of the vascular cambium clearly affect the shape of the tree, as in Pinus radiata
      (D. Don.).

PMID- 15520569
TI  - Measuring the domain completeness of the Nursing Interventions Classification in
      parish nurse documentation.
AB  - As the healthcare industry moves toward automating the patient record, care
      providers have been challenged to capture their domain of practice in a
      computerized format. Nurses have responded by developing a number of American
      Nurses Association (ANA) recognized nursing standardized terminologies. This
      study measured the domain completeness and uses of one such terminology, the
      Nursing Interventions Classification (NIC), within the specialty of parish
      nursing, a spiritually focused, community-based practice. Documentation samples
      from 170 health records submitted by 13 parish nurses in 7 sites across the
      country, stratified by urban, suburban, and rural sites were used. The nursing
      interventions that were documented in 1607 unique interactions in these charts
      were mapped into NIC using standardized mapping procedures. Intercoder
      reliability was assessed, with a final kappa of 0.92 (93% agreement) and code
      recode reliability with a kappa of 0.72 (74% agreement). Overall, 93% of the 3059
      interventions mapped into NIC. Recommended modifications in existing NIC labels
      and additional NIC labels are presented. The results suggest that NIC supports
      the documentation of parish nursing practice and has the capability of capturing
      the spiritual dimension of care.

PMID- 15520570
TI  - Conducting a client-focused survey using e-mail.
AB  - An e-mail listserv was used to recruit participants, administer a survey, send
      electronic gift certificates, and disseminate the findings of a study of
      psychological responses to being a carrier of the gene for phenylketonuria, a
      rare genetic disease. The majority of responses to the call for participants were
      received within the first 24 hours, and most surveys (n = 83) were returned via e
      mail within 5 days. The use of e-mail allowed more opportunities for researcher
      participant interaction than Web-based surveys, but the return rate of 51% may
      reflect concerns about privacy when e-mail addresses are required.

PMID- 15520571
TI  - A process for consolidation of redundant documentation forms.
AB  - Forms capturing redundant data can lead to duplicate documentation. This can be a
      source of patient and staff frustration, as well as data errors. The definition
      of a process aimed at examining the data captured on forms documenting similar
      aspects of patient care is necessary to avoid this problem of duplicate
      documentation. A data-driven systematic process for consolidation of the multiple
      redundant forms used in various patient care areas across a healthcare delivery
      system is proposed and tested using the 21 intake forms currently used by a
      regional Health Maintenance Organization (HMO). The analytic and subsequent
      reporting processes used in this project provide a systematic method of forms
      consolidation that can be applied to other settings.

PMID- 15520572
TI  - Computerized versus paper-and-pencil testing methods for a nursing certification
      examination: a review of the literature.
AB  - In conjunction with the decision of the Oncology Nursing Certification
      Corporation (ONCC) to computerize its examinations, the literature was reviewed
      to identify comparative studies of computerized versus paper-and-pencil testing
      methods and to determine the relative advantages of each. Data sources included
      journal articles and newsletter features identified via the ERIC, CINAHL, and
      PubMed databases or through frequent citation in the literature. The majority of
      studies found test scores to be independent of delivery mode. Several advantages
      of computerized testing were identified, including scheduling convenience,
      instant scoring capability, and enhanced security. One disadvantage may be an
      increase in testing anxiety for those without previous experience, although
      results in this area were mixed. Finally, studies and surveys often indicate an
      acceptance and preference for linear computer-based testing (CBT) by examinees.

PMID- 15520574
TI  - The evolution and evaluation of videoconferencing technology for graduate nursing
      education.
AB  - The Integrated Services Digital Network H.323 (ISDN), which has been in use for
      the past 20 years often requires a dedicated telephone line and other equipment
      to implement. Consequently, expansion of ISDN-based videoconferencing requires
      infrastructure not always accessible in those areas that are most in need of
      technological connections. New H.323 technology using Internet Protocol H.320
      (IP) connectivity can accommodate the use in a variety of videoconferencing
      software and fill this void as demonstrated by an experiment conducted live at
      the Syllabus Web '99 conference. When a faculty group were unable to secure ISDN
      connections to demonstrate their clinical evaluation of Family Nurse Practitioner
      (FNP) students using videoconferencing technology, an ad hoc group of computer
      experts, educators, instructional design specialists, and corporate sponsors
      collaborated to design a multipoint PC-based connection using IP connectivity.
      This article describes the first application of this technology, the evolution of
      ISDN and IP systems in nursing education and practice, and suggests appropriate
      future trends for their utility in nursing.

PMID- 15520575
TI  - An experience with an online learning environment to support a change in practice
      in an emergency department.
AB  - Providing continuing education to support a change in practice for a busy
      Emergency Department poses a challenge. Factors such as shift work, high patient
      acuity, and unpredictable patient flow create barriers to traditional methods of
      delivery of a comprehensive educational experience. This article describes an
      experience with introducing a change in practice using an innovative Web-based
      delivery plan. Specific strategies were employed to address presentation of
      content, application of knowledge, establishment of a shared understanding, and
      enhancement of communication opportunities. The Web-based learning environment
      proved to be a successful means of providing nurses with a collaborative learning
      experience around a new practice issue. This experience also highlighted the need
      for a new skill set for learners and educators using online learning
      technologies.

PMID- 15520581
TI  - Data mining as a tool for research and knowledge development in nursing.
AB  - The ability to collect and store data has grown at a dramatic rate in all
      disciplines over the past two decades. Healthcare has been no exception. The
      shift toward evidence-based practice and outcomes research presents significant
      opportunities and challenges to extract meaningful information from massive
      amounts of clinical data to transform it into the best available knowledge to
      guide nursing practice. Data mining, a step in the process of Knowledge Discovery
      in Databases, is a method of unearthing information from large data sets. Built
      upon statistical analysis, artificial intelligence, and machine learning
      technologies, data mining can analyze massive amounts of data and provide useful
      and interesting information about patterns and relationships that exist within
      the data that might otherwise be missed. As domain experts, nurse researchers are
      in ideal positions to use this proven technology to transform the information
      that is available in existing data repositories into useful and understandable
      knowledge to guide nursing practice and for active interdisciplinary
      collaboration and research.

PMID- 15520582
TI  - Internet teaching methods for use in baccalaureate nursing education.
AB  - The advent of technology has had a profound influence on nursing education. As an
      example, use of the Internet is continually gaining importance. The Internet
      allows students to learn in a classroom, via distance education, or at home. Many
      nurse educators now adapt traditional content with ease, using alternative
      teaching methods that integrate Internet technology. In this article, a variety
      of alternative adaptations are considered. Focused on baccalaureate nursing
      education, this article presents a limited review and critique of the literature
      regarding successful use of the Internet.

PMID- 15520584
TI  - Integration of Internet-based learning and traditional face-to-face learning in
      an RN-BSN course in Korea.
AB  - This article describes the development of and student satisfaction with a
      distance learning course using both online and face-to-face methods in an RN-BSN
      program in Korea. Four steps were used for course development: (1) assessment of
      students' learning needs and determination of objectives of the course, (2)
      designing of module/assignment instructions, (3) development of the Internet
      based learning platform, and (4) evaluation of course and Internet-based learning
      platform. Student satisfaction was evaluated by using a 4-point Likert-type
      questionnaire. Forty-eight (92.3%) questionnaires were returned. Overall
      satisfaction with this course was high (X = 3.29). Appropriateness of learning
      methods (X = 3.35) was rated the most satisfactory, followed by appropriateness
      of content (X = 3.31). Most of the students enjoyed the course and they wanted
      more nursing courses to be offered through the online and on-site format. On the
      basis of the findings, additional courses using both online and face-to-face
      methods for RN-BSN students should be developed and implemented for RN-BSN
      nursing programs in Korea.

PMID- 15520585
TI  - The physical, behavioral, and psychosocial consequences of Internet use in
      college students.
AB  - The purposes of this study were to identify the physical, behavioral, and
      psychosocial consequences of Internet use in undergraduate college students; and
      to evaluate whether time, social norms, and adopter category predict the
      consequences of Internet use. Rogers' model for studying consequences of
      innovation was adapted for this study. A descriptive, correlational design was
      used. Convenience sampling yielded 293 undergraduate students who answered the
      online survey. Consequences of Internet use were assessed with the researcher
      developed instrument, the Internet Consequences Scale (ICONS). Mean scores on the
      behavioral and psychosocial subscales of the ICONS indicated positive
      consequences of Internet use, while the physical consequences subscale revealed
      negative consequences. Multiple regression analyses revealed a small, but
      significant, amount of variance in consequences of Internet use that could be
      explained by time, social norms, and adopter category, thus supporting the
      adapted model for the study of consequences of Internet use in college students.

PMID- 15520586
TI  - Computer simulation of the human respiratory system for educational purposes.
AB  - The main objective of this study was the development of a computer simulation
      system for the human respiratory system, in order to educate students of nursing.
      This approach was based on existing mathematical models and on our own
      constructed specific functions. For the development of this educational tool the
      appropriate software packages were used according to the special demands of this
      process. This system is called ReSim (Respiratory Simulation) and consists of two
      parts: the first part deals with pulmonary volumes and the second one represents
      the mechanical behavior of lungs. The target group evaluated ReSim. The outcomes
      of the evaluation process were positive and helped us realize the system
      characteristics that needed improvements. Our basic conclusion is that the
      extended use of such systems supports the educational process and offers new
      potential for learning.

PMID- 15520587
TI  - Survey reveals role, compensation of nurse informaticists.

PMID- 15520588
TI  - Lifelong learning, professional development, and informatics certification.

PMID- 15520594
TI  - Enhancing survey data collection among youth and adults: use of handheld and
      laptop computers.
AB  - Tobacco use, alcohol and other drug use, early sexual behavior, dietary
      practices, physical inactivity, and activities that contribute to unintentional
      and intentional injuries are a significant threat to the health of young people.
      These behaviors have immediate and long-term consequences and contribute to
      diminished health, educational, and social outcomes. Research suggests that
      health risk behaviors exhibited during adolescence and adulthood have their
      origins earlier in childhood and preventive interventions are less successful
      after the risk behaviors have begun. Therefore, efforts to prevent health risk
      behaviors are best initiated in late childhood or early adolescence. However, to
      document the efficacy of these efforts, reliable, valid, and parent/child
      friendly systems of data collection are required. Computerized data collection
      for research has been found to improve privacy, confidentiality, and portability
      over the paper-and-pencil method, which, in turn, enhances the reliability of
      sensitive data such as alcohol use or sexual activity. We developed programming
      tools for the personal computer and a handheld personal data assistant to offer a
      comprehensive set of user interface design elements, relational databases, and
      ample programming languages so that adults could answer 261 items and youth 346
      items. The purpose of the article was to describe an innovative handheld computer
      assisted survey interview method of collecting sensitive data with children aged
      9 to 11. The method was developed as part of a large multisite, national study to
      prevent substance use.

PMID- 15520595
TI  - Installing computers in older adults' homes and teaching them to access a patient
      education web site: a systematic approach.
AB  - This article describes the experiences of nurses who, as part of a large clinical
      trial, brought the Internet into older adults' homes by installing a computer, if
      needed, and connecting to a patient education Web site. Most of these patients
      had not previously used the Internet and were taught even basic computer skills
      when necessary. Because of increasing use of the Internet in patient education,
      assessment, and home monitoring, nurses in various roles currently connect with
      patients to monitor their progress, teach about medications, and answer questions
      about appointments and treatments. Thus, nurses find themselves playing the role
      of technology managers for patients with home-based Internet connections. This
      article provides step-by-step procedures for computer installation and training
      in the form of protocols, checklists, and patient user guides. By following these
      procedures, nurses can install computers, arrange Internet access, teach and
      connect to their patients, and prepare themselves to install future generations
      of technological devices.

PMID- 15520597
TI  - Wireless technology improves nursing workflow and communications.
AB  - Inpatient healthcare delivery involves complex processes that require
      interdisciplinary teamwork and frequent communication among physicians, nurses,
      unit secretaries, and ancillary staff. Often, these interactions are not at a
      nursing unit, or near a phone. In an effort to address the inefficiencies of
      these workflow processes and communications, St. Agnes HealthCare, Baltimore, MD,
      installed a new hands-free communications system that uses a wireless network,
      voice recognition, and a small wearable badge. Developed by Vocera, the
      communications system permits one-button access to others on the system or
      connects to outside phones through PBX integration. While many agree that today's
      technology has the potential to positively impact nursing care delivery, St.
      Agnes HealthCare and Vocera, with assistance from First Consulting Group, decided
      to conduct a comprehensive benefits study in December 2003 to quantify the impact
      of this communications system on workflow and communications. The results
      identified a number of significant findings that demonstrate its value from a
      quantitative and qualitative standpoint. The following article describes this
      study and its findings.

PMID- 15520598
TI  - An evaluation of an online intervention to provide social support and health
      education.
AB  - Managing chronic illness in the isolation of rural environments is challenging
      for women who lack access to personal sources of social support and health
      information. The Women to Women project was designed to provide chronically ill
      rural women access to support and health information via electronic means. This
      article reports on the acquisition of computer skills, the perceptions of
      importance of various aspects of the intervention, and an assessment of women's
      overall satisfaction with participation in the research project. Findings
      indicate that the women's self-ratings of computer skills improved significantly
      over the 22-week intervention and that highly interactive features of the project
      were rated as most important by the participants. Overall, women found the
      program beneficial in assisting them to better manage their chronic illness.

PMID- 15520603
TI  - Ever-present adverse effects.

PMID- 15520599
TI  - Recruitment of research participants through the Internet.
AB  - Despite an increasing amount of Internet research, issues in recruitment for
      studies in this environment rarely have been discussed. The purpose of this
      article is to provide some future directions for participant recruitment via the
      Internet, based on the experiences of recruiting participants for three Internet
      survey studies. The issues in the recruitment process include those related to
      low response rates, selected groups of participants, the importance of timing,
      and potential ethical issues. Based on the discussion of the issues, the
      following suggestions are proposed for future recruitment through the Internet:
      use of creative motivation strategies; sensitivity to the gender, ethnicity, and
      socioeconomic status of potential participants; consideration of the timing of
      data collection; and sensitivity to potential ethical issues.

PMID- 15520604
TI  - The multiple facets of treatment-resistant depression.

PMID- 15520605
TI  - Therapeutic alternatives for difficult-to-treat depression: a narrative review of
      the state of the evidence.
AB  - Despite the large number of depressed patients who do not respond to first-line
      antidepressants, the evidence base of alternate strategies is quite thin. In this
      article, a simple 5-stage system for categorizing treatment-resistant depression
      (TRD) is described and the evidence pertaining to the major strategies currently
      utilized is summarized using four grades, ranging from D (case reports only) to A
      (multiple positive placebo-controlled trials). It is concluded that the level of
      evidence supporting many of the contemporary strategies used for TRD (eg,
      combinations of antidepressants and augmentation with medications such as
      pindolol, buspirone, or modafinil) is scanty at best. Even the fundamental
      question concerning "to augment or to switch" is not answerable with available
      data. It is noted that the best-documented treatments (ie, lithium augmentation,
      switching to a monoamine oxidase inhibitor, and electroconvulsive therapy) are
      among the least utilized. This state of affairs will improve with completion of
      the studies of Systematic Treatment Alternatives to Relieve Depression, a large
      multicenter study of difficult-to-treat depression funded by the National
      Institute of Mental Health. There is a need for greater collaboration among
      academicians and organizations, such as the American Psychiatric Association, the
      National Institute of Mental Health, and the pharmaceutical industry, to ensure
      that sufficient research is conducted so that clinician's choices for patients
      with TRD can be guided by empirical evidence.

PMID- 15520606
TI  - Therapy of treatment resistant depression: focus on the management of TRD with
      atypical antipsychotics.
AB  - Treatment-resistant depression (TRD) represents a significant challenge for
      physicians. About one third of patients with major depressive disorder fail to
      experience sufficient symptom improvement despite adequate treatment. Despite
      this high occurrence of TRD there was no general consensus on diagnosis criteria
      for TRD until 1997 when researchers proposed a model of defining and staging TRD.
      In 1999, others defined operational criteria for the definition of TRD. Treatment
      of TRD is commonly separated into pharmacologic and nonpharmacologic methods.
      This review gives a short overview of these two methods. The nonpharmacologic
      methods include psychotherapy, electroconvulsive therapy, and vagus nerve
      stimulation. Pharmacologic methods include switching to another antidepressant
      monotherapy, and augmentation or combination with two or more antidepressants or
      other agents. This review especially focuses on the augmentation of the
      antidepressant therapy with atypical antipsychotics.

PMID- 15520607
TI  - A review of the treatment for refractory obsessive-compulsive disorder: from
      medicine to deep brain stimulation.
AB  - This article provides an overview of the etiology, epidemiology, and first-line
      treatment options for obsessive-compulsive disorder (OCD). The subject of
      treatment-resistant and treatment-refractory OCD is then discussed, including a
      definition of these often-debated terms, and the latest treatment options
      delineated. This includes a review of the latest research concerning the
      pharmacological agents that have been studied as monotherapy or augmenting agents
      for the treatment of OCD, the use of experimental medications and procedures,
      treatment with reversible, minimally invasive procedures, such as vagal nerve
      stimulation and transcranial magnetic stimulation, invasive but the potentially
      reversible deep brain stimulation, and irreversible lesioning with ablative
      psychosurgery. A discussion of the role of psychotherapy in the treatment of OCD
      is also included.

PMID- 15520608
TI  - Clinical experience with aripiprazole treatment in ten elderly patients with
      schizophrenia or schizoaffective disorder: retrospective case studies.
AB  - BACKGROUND: Clinical trials of aripiprazole, a recently Food and Drug
      Administration-approved atypical antipsychotic, included elderly patients, but
      more data are needed on the effects of aripiprazole in this population,
      especially those with comorbid medical illnesses. OBJECTIVE: To assess the
      response and safety of aripiprazole treatment in elderly patients with
      schizophrenia or schizoaffective disorder. METHOD: Data was obtained by
      retrospective review of medical records. Aripiprazole was used to treat 10
      elderly hospitalized patients between 62 and 85 years of age who manifested signs
      of psychosis related to schizophrenia or schizoaffective disorder. All patients
      had been treated previously with atypical and classic antipsychotics. Response
      was assessed by clinical observation of patients' behavior and Clinical Global
      Impression Scale assigned retrospectively. RESULTS: Seven patients responded to
      treatment, two did not respond, and one had a partial response. The mean Clinical
      Global Impression Scale scores improved from 6 (severely ill) at baseline to 2.3
      (much improved) at discharge. Treatment was discontinued in the two patients who
      did not respond. Of the seven patients who responded, four presented with
      positive symptoms and showed significant improvement while three presented with
      positive and negative symptoms and both symptoms improved significantly. Four
      patients had preexisting extrapyramidal symptoms (EPS) and these symptoms
      decreased in three patients. In addition, two patients were able to discontinue
      antiparkinson medications. One patient who had severe tardive dyskinesia showed
      significant improvement in the dyskinetic symptoms. Four patients showed postural
      hypotension (without clinical symptoms) which resolved over time without
      treatment. Six patients showed a mean weight loss of 5.2 lbs. No adverse
      consequences occurred when divalproex sodium, carbamazepine, clonazepam or
      citalopram were given concurrently. CONCLUSION: The reduction of both positive
      and negative symptoms of schizophrenia and the lack of significant EPS, tardive
      dyskinesia, sedation, weight gain, anticholinergic effects, and QTc prolongation
      gives preliminary indication that aripiprazole may be a safe and effective
      medication for elderly patients with schizophrenia or schizoaffective disorder.

PMID- 15520609
TI  - The role of atypical antipsychotics in glucose/insulin dysregulation and the
      evolving role of the psychiatrist in a new era of drug treatment options.
AB  - This article examines the issue of atypical antipsychotics, glucose/insulin, and
      other metabolic derangements (ie, metabolic syndrome), including a general
      introduction to the health concerns of our patients, a review of the literature,
      possible mechanisms of antipsychotic induced glucose dysregulation, monitoring
      approaches, and management and prevention of metabolic syndrome. Literature
      review leads to mechanism hypotheses and risk estimations, leading to guidelines
      for monitoring and treatment. The patient population suffers from a higher degree
      of baseline metabolic dysregulation resulting in cardiovascular disease through
      components of the metabolic syndrome, and this risk increases with administration
      of atypical antipsychotic medication at different rates, depending on both drug
      and patient risk factors. The growing knowledge of mechanisms behind drug induced
      glucose/insulin and other metabolic dysregulation, as well as advances in
      pharmacogenomics, will help refine drug selection and monitoring for adverse,
      life-threatening metabolic effects.

PMID- 15520610
TI  - Overcoming our limits.

PMID- 15520611
TI  - The truth, the whole truth, and statistical parametric maps.

PMID- 15520612
TI  - An old transmitter in a new millennium.

PMID- 15520613
TI  - Adrenergic pharmacology: focus on the central nervous system.
AB  - Norepinephrine and epinephrine are involved in the control of several important
      functions of the central nervous system (CNS), including sleep, arousal, mood,
      appetite, and autonomic outflow. Catecholamines control these functions through
      activation of a family of adrenergic receptors (ARs). The ARs are divided into
      three subfamilies (alpha1, alpha2, and beta) based on their pharmacologic
      properties, signaling mechanisms, and structure. ARs in the CNS are targets for
      several therapeutic agents used in the treatment of depression, obesity,
      hypertension, and other diseases. Not much is known, however, about the role of
      specific AR subtypes in the actions of these drugs. In this paper, we provide an
      overview of adrenergic pharmacology in the CNS, focusing on the pharmacologic
      properties of subtype-selective AR agonists and antagonists, the accessibility of
      these drugs to the CNS, and the distribution of ARs in different areas of the
      brain.

PMID- 15520614
TI  - Role of norepinephrine in the pathophysiology of neuropsychiatric disorders.
AB  - The concatenation of convergent lines of evidence from basic to clinical research
      continues to reveal that norepinephrine (NE) is a crucial regulator of a myriad
      of behaviors ranging from stress response to memory formation. Furthermore, many
      neuropsychiatric disorders involve neurocircuitry that is directly modulated by
      NE. This report summarizes the physiological roles of NE, as well as the main
      findings implicating a role for NE system dysfunction in mood and anxiety
      disorders, posttraumatic stress disorder, attention-deficit/hyperactivity
      disorder, and Alzheimer's disease. In each of these disorders, there appears to
      be a complex dysregulation of NE function, with changes in locus ceruleus firing,
      NE availability, and both pre- and postsynaptic receptor regulation. Many
      symptoms of these disorders are attributable to abnormalities within distributed
      neural circuits regulated by NE. Appreciation of NE's role in modulating the
      neural circuitry mediating cognition and affect should help elucidate the
      pathophysiology of a variety of neuropsychiatric disorders and the development of
      novel treatments.

PMID- 15520615
TI  - Function and regulation of monoamine transporters: focus on the norepinephrine
      transporter.
AB  - Presynaptic norepinephrine transporters (NETs) mediate the rapid clearance of
      norepinephrine from synaptic spaces. NET is a member of the Na+ and Cl- -coupled
      neurotransmitter transporter gene family, which also includes the serotonin and
      dopamine transporters. Recent studies reveal that these transporter molecules
      might be a dynamic component of synaptic plasticity, rather than a constitutive
      determinant of neurotransmitter levels in synaptic spaces. Recognition that
      cellular signaling molecules and transporter ligands, including cocaine,
      amphetamines, and antidepressants, can modify transporter intrinsic activity,
      trafficking, phosphorylation, and protein levels suggests opportunities for
      revealing unknown mechanisms of drug action. Control of these properties of
      transporter function may allow for the development of new strategies to modulate
      monoaminergic neurotransmission and identify regulatory pathways that may be
      compromised in psychiatric, neurologic, and neurodegenerative disorders.

PMID- 15520616
TI  - Noradrenergic pathology in psychiatric disorders: postmortem studies.
AB  - In this paper, we review research utilizing postmortem brain tissue in order to
      investigate the potential neuropathology of the noradrenergic system in
      psychiatric disorders. The postmortem tissue approach to the study of the
      noradrenergic system has been used primarily in investigations of the biology of
      suicide and depression. Findings from postmortem studies provide data generally
      consistent with the hypothesis that a norepinephrine deficiency exists in
      depression, and possibly in the victims of suicide. However, postmortem studies
      do not presently provide irrefutable evidence of noradrenergic neuropathology.
      Technical shortcomings, issues of reproducibility, and the strengths of
      postmortem research are reviewed. More rigorously performed postmortem research
      is needed to aid researchers in pinpointing specific neuropathologies associated
      with psychiatric disease.

PMID- 15520617
TI  - Radioligands for PET and SPECT Imaging of the central noradrenergic system.
AB  - In the central nervous system, the neurotransmitter norepinephrine is involved in
      normal physiology, neuropsychiatric disorders, and the effects of numerous drugs.
      Although alterations of the central noradrenergic system are involved in the
      pathophysiology and pharmacotherapy of mood disorders, the basis and nature of
      these changes remain unresolved. Positron emission tomography (PET) and single
      photon emission computed tomography (SPECT) imaging agents will be valuable for
      further elucidating the roles of norepinephrine in health and disease. This
      review discusses PET and SPECT radioligands that have been developed for the
      enzymes, receptors, and transporters involved in noradrenergic neurotransmission.
      Currently, imaging agents that exhibit specific in vivo uptake in the brain have
      been described for monoamine oxidase A and beta-adrenergic receptors, but have
      not undergone detailed evaluation or experimental application. Based on the
      successful development and utilization of in vivo imaging agents for elements of
      the central dopaminergic and serotoninergic systems, PET and SPECT radioligands
      are expected to serve as new tools for studying the physiology, pathophysiology,
      and pharmacology of the central noradrenergic system.

PMID- 15520618
TI  - Efficacy of noradrenergic-selective agents in the treatment of neuropsychiatric
      diseases.
AB  - In recent years, a number of antidepressants with varying degrees of selectivity
      for the noradrenergic neurotransmitter system have become available. However,
      these agents represent a pharmacologically heterogeneous group and differ in
      terms of their precise side-effect profile and, possibly, their clinical
      efficacy. Bupropion, which is thought to act on both the dopamine and
      norepinephrine (NE) systems, has not been widely used as an antidepressant and
      has more recently been licensed as adjunctive therapy for smoking cessation. The
      serotonin-NE reuptake inhibitors venlafaxine and nefazodone, the noradrenergic
      and specific serotonergic antidepressant mirtazapine, and the selective NE
      reuptake inhibitor reboxetine (the only truly NE-selective agent available) have
      all demonstrated efficacy in the treatment of depressive disorders. Evidence is
      now emerging for their use in the treatment of anxiety and panic disorders. There
      is some suggestion of a role for noradrenergic agents in other disorders,
      including attention-deficit/hyperactivity disorder and social phobia. The full
      range of disorders for which noradrenergic agents can be used remains to be seen
      and further research in this area is necessary.

PMID- 15520619
TI  - Response of the norepinephrine system to antidepressant drugs.
AB  - Environmental stimuli and drugs affect the norepinephrine (NE) system and may be
      linked to the manifestation and treatment of anxiety and affective disorders. The
      activity of locus ceruleus NE neurons in the brainstem can alter the function of
      forebrain structures associated with several psychiatric disorders. In
      particular, NE neurons send and receive projections from sensory afferents,
      limbic areas, and cortical areas implicated in higher-order brain malfunctions
      and the symptomatology of anxiety and affective disorders. In turn, anxiolytic
      and antidepressant drugs are able to offset perturbations of NE activity and
      forebrain structures with a time course congruent with their therapeutic action.
      All antidepressants, even the agents selective for other biogenic amines or
      peptides, act on the NE system. In the present review, the effects of
      antidepressants on NE neurons are summarized and applied to the treatment of
      neuropsychiatric disorders, with emphasis placed on mechanisms of action.

PMID- 15520622
TI  - What about celebrex?

PMID- 15520621
TI  - Antiviral drugs for prophylaxis and treatment of influenza.

PMID- 15520623
TI  - Coauthorship in pathology, a comparison with physics and a survery-generated and
      member-preferred authorship guideline.
AB  - In a large and detailed survey of scientific coauthorship in pathology, 3500
      members of the US and Canadian Academy of Pathology (USCAP) were surveyed via the
      Internet with a final response rate of 22.5%. The results were compared with a
      previous survey of members of the American Physical Society (APS). The fields are
      found to be very similar. For example, there is no well-defined way to determine
      coauthorship: the byline is arrived at without the use of public coauthorship
      standards according to 90% of respondents (92% in physics). A substantial amount
      of inappropriate authorship is present in both fields using a variety of
      authorship guidelines. For example, using the guideline of the International
      Committee of Medical Journal Editors (the "Uniform Requirements for Manuscripts
      Submitted to Biomedical Journals" [ICMJE]), the average number of coauthors
      judged to be inappropriate in pathology on papers with 4 coauthors is 1.0 (1.2 in
      physics), and using the guideline requiring "direct contributions to scientific
      discovery or invention," we find 1.6 (1.5 in physics). Finally, it is suggested
      that authorship guidelines should be constructed by public surveys rather than
      closed-door committees: an authorship guideline constructed from previous survey
      feedback (from APS members) was found to be preferable to USCAP members (it
      received 40% of the vote, the ICMJE received 24% of the vote).

PMID- 15520624
TI  - Changes in children's exposure as a function of age and the relevance of age
      definitions for exposure and health risk assessment.
AB  - OBJECTIVE: The objective of this study was to review and synthesize the existing
      exposure information available to support the characterization and estimation of
      children's environmental health risks as a function of age. METHOD: This includes
      a review of the existing peer-reviewed literature and reports from the US
      Environmental Protection Agency (EPA) up through January 1, 2003 for information
      about exposure data for American children with a focus on identifying the age
      categories used and data gaps that limit our ability to estimate children's risks
      from exposure to environmental hazards. RESULTS: On the basis of this synthesis,
      several key data gaps emerge that suggest some areas in which exposure assessors
      may want to focus attention, including current breast milk consumption by infants
      and breastfeeding information for children over age 1 year; children's food
      handling practices and how these lead to exposure (eg, by eating with dirty hands
      or by eating food that has dropped onto a contaminated surface); fish-intake
      rates for young children and for children whose families include sport fishers or
      whose families rely on self-caught fish for sustenance; incidental and
      intentional soil intake by children; soil adherence for dermal exposure;
      relationships between various microactivities, macroactivities, and
      microenvironments where children spend time; and a correlation between exposure
      factors and growth (ie, how children's exposure behaviors change over time). In
      contrast, relatively good exposure information exists for characterizing
      children's growth and water ingestion, and at least some exposure information
      exists for the wide ranges of exposures of regulatory interest. CONCLUSION: Given
      the currently available data, exposure assessors can estimate children's
      potential health risks from a number of different types of exposure, but
      longitudinal data are needed to reduce the significant uncertainties that arise
      from reliance on currently available data, and a number of dose-response
      challenges remain.

PMID- 15520625
TI  - Violence, sex and profanity in films: correlation of movie ratings with content.
AB  - CONTEXT: Children's exposure to violence, sexual themes, profanity, and the
      depiction of substances in movies remains a source of parental and public health
      concern. However, limited research quantifies the correlations between movie
      content, ratings, and economics or addresses the issue of ratings "creep."
      OBJECTIVES: To characterize available information about violence, sex, and
      profanity content of movies as a function of rating; quantitatively explore the
      relationships between content, ratings, and economic information; compare the
      amount of violence in animated and non-animated G-rated films; and test for a
      trend of decreased stringency of rating criteria (ie, "ratings creep") as a
      function of time. DESIGN: We developed a complete database of movie ratings
      available from the Motion Picture Association of America (MPAA) to characterize
      the content information (including any indicated reasons noted for ratings) for
      all movies released between January 1, 1992 and December 31, 2003. We then added
      to the database the three Kids-in-Mind content-based scores for: (1) violence and
      gore, (2) sex and nudity, and (3) profanity; and the 15 categories of information
      from Screen It!, which began providing information in mid-1996. Finally, we
      obtained information on gross revenues and movie budgets from the IMDbPro. We
      performed statistical analyses to correlate the content-based scores with the
      overall rating and rating reasons assigned by the MPAA; to test the hypothesis
      that age-based ratings became less stringent over time; to explore correlations
      between film content, ratings, and available economic information; to compare the
      amount of violence in animated and non-animated G-rated films; and to
      characterize the available information about the depiction of substances in
      films. MAIN OUTCOME OF MEASURES: Description of movie ratings, correlation of
      content with rating, and statistical results. RESULTS: Comparing the content
      based scores for different movie ratings, we find large variability exists in the
      types of content that receive different MPAA ratings, and good correlation
      between the content-based scores assigned by Kids-in-Mind and Screen It! The MPAA
      rating reasons correlate with higher scores assigned to content-based ratings,
      and the number of reasons indicated increases with the age-based rating category.
      We found significantly higher rated content in movies as a function of time,
      suggesting that the MPAA applied less stringency in its age-based ratings over
      time for the period of 1992-2003. Animated films rated G by the MPAA received a
      significantly higher content-based score for violence on average than non
      animated films rated G (P < .05). With respect to information about the depiction
      of substances, the MPAA mentioned alcohol or drugs in its rating reason for 226
      films (18%), while Screen It! identified depiction or use of tobacco, alcohol,
      and/or drugs in 1211 films (95%), including 26 of the 51 G-rated films (51%). We
      found significantly higher gross revenues for PG-13- and R-rated films when
      comparing films that received an MPAA rating reason for violence compared with
      those films that did not (P < .001 based on 2-sided t-tests with unequal
      variances for both of the separate tests of PG-13- and R-rated films).
      CONCLUSIONS: Parents and physicians should be aware that movies with the same
      rating can differ significantly in the amount and types of potentially
      objectionable content. Age-based ratings alone do not provide good information
      about the depiction of violence, sex, profanity, and other content, and the
      criteria for rating movies became less stringent over the last decade. The MPAA
      rating reasons provide important information about content, but they do not
      identify all types of content found in films and they may particularly miss the
      depiction of substances.

PMID- 15520626
TI  - Etiology and pathogenesis of necrolytic migratory erythema: review of the
      literature.
AB  - CONTEXT: Necrolytic migratory erythema (NME) is a characteristic skin condition
      seen in the presence of a pancreatic glucagonoma. The presence of NME in the
      absence of a pancreatic tumor has been termed the pseudoglucagonoma syndrome. In
      such cases, NME is commonly associated with conditions, such as liver disease,
      inflammatory bowel disease, pancreatitis, malabsorption disorders (ie, celiac
      sprue), and other malignancies. There are many theories on the pathogenesis of
      NME, which include the direct action of glucagon in inducing skin necrolysis,
      hypoaminoacidemia-inducing epidermal protein deficiency and necrolysis, a
      nutritional or metabolic deficiency of zinc or essential fatty acids, liver
      disease, glucagon induction of inflammatory mediators, a substance secreted from
      pancreatic and other visceral tumors associated with NME, and generalized
      malabsorption. OBJECTIVE: To present a review of the literature on the clinical
      presentation, etiology, pathogenesis, and treatment of NME. DESIGN: Review of the
      literature on NME occurring in patients both with and without a pancreatic
      glucagonoma. METHODS: We performed a PubMed review of the literature on the
      etiology and pathogenesis of NME to identify case reports and reviews published
      in both the internal medicine and dermatology literature. RESULTS: Our literature
      review encompassed 17 primary case reports and literature reviews published in
      the dermatologic and internal medicine literature on NME in patients both with
      and without a pancreatic glucagonoma. Although we found no clear consensus among
      the investigators of a universally accepted pathogenesis for NME, we did identify
      4 main categories of etiologic/pathogenetic mechanisms for NME (glucagon excess,
      nutritional deficiencies, inflammatory mediators, and liver disease) that were
      discussed by many of the investigators and validated by both clinical and
      scientific evidence. CONCLUSION: The exact pathogenesis and treatment of NME
      remain ill-defined despite many case reports and studies on NME in the
      literature. The many systemic diseases and nutritional deficiencies that have
      been found to be associated with NME suggest a multifactorial model for the
      pathogenesis of the disease. The most comprehensive, postulated mechanism for NME
      involves a combination of zinc, amino acid, and fatty acid deficiencies (arising
      from a wide variety of causes, such as dietary insufficiency, malabsorption
      syndromes, liver disease, elevated glucagon levels, and disorders of metabolism)
      that contributes to increased inflammation in the epidermis in response to trauma
      and to the necrolysis observed in NME. The importance of gaining an understanding
      of the etiology and pathogenesis of NME lies in the fact that there is no
      universally accepted mechanism of pathogenesis for NME, and that the only
      treatment reported to resolve the rash in these patients is to adequately
      identify and treat the underlying associated systemic condition or nutritional
      deficiency.

PMID- 15520628
TI  - Alendronate and risedronate for the treatment of postmenopausal osteoporosis:
      clinical profiles of the once-weekly and once-daily dosing formulations.
AB  - OBJECTIVE: The objective of this review is to present the clinical profiles of
      the once-weekly and once-daily dosing formulations of alendronate and
      risedronate, the 2 bisphosphonates currently available in the United States for
      the prevention and treatment of postmenopausal osteoporosis. DATA SOURCE/STUDY
      SELECTION: Data were obtained from a MEDLINE literature search of all English
      language articles published between January 1996 and April 2004 using generic
      names of the bisphosphonates alendronate and risedronate. Results were refined by
      incorporating terms such as "osteoporosis," "bone mineral density," "fracture
      risk," and "adverse events." Randomized, controlled trials of once-daily and once
      weekly bisphosphonate therapies were selected. Also selected for review were post
      hoc analyses and extension studies of the original controlled trials, including
      more recent data from published abstracts from scientific meetings. DATA
      EXTRACTION: Relevant portions of articles obtained from the literature search
      were used to summarize the efficacy and tolerability of the 2 therapies.
      CONCLUSIONS: In prospective trials, both bisphosphonates were effective in
      reducing vertebral and hip fractures in women with postmenopausal osteoporosis.
      In the only prospective trial evaluating hip fracture risk reduction as the
      primary end point, risedronate was effective at reducing hip fracture vs placebo.
      Both alendronate and risedronate are available in once-weekly formulations that
      have efficacy and tolerability profiles similar to the once-daily doses.
      Clinicians should review all available data for both agents as well as the
      medical history of the patient to make the most appropriate treatment choice.

PMID- 15520627
TI  - Anticoagulation therapy for venous thromboembolism.
AB  - CONTEXT: On the basis of theoretical rationale, heparoids and vitamin K
      antagonists are prescribed to prevent complications of venous thromboembolism
      (VTE, including pulmonary emboli [PE] and deep vein thrombosis [DVT]). They have
      been employed as the standard of care for treatment of VTE for over 40 years.
      OBJECTIVE: Critique the evidence supporting the efficacy of anticoagulants for
      the treatment of VTE in reducing morbidity and/or mortality. DATA SOURCES: This
      includes a search of reference lists and Medline. STUDY SELECTION: This includes
      studies concerning the diagnosis and incidence of PE and DVT, efficacy of
      anticoagulants in preventing complications, risks of anticoagulant therapy, and
      the costs of diagnosis and the treatment of VTE. DATA EXTRACTION: I analyzed
      references cited in reviews and meta-analyses of VTE, and from Medline searches
      concerning diagnosis and treatment. The data quality and validity of studies
      depended on the consistency of findings and statistical significance of the data.
      DATA SYNTHESIS: No placebo-controlled trials of anticoagulants as treatment of PE
      with objective criteria for diagnosis have been published. Three randomized
      trials of anticoagulants vs no anticoagulants in DVT showed no benefit with
      heparin and vitamin K antagonists (combined all-cause mortality: anticoagulants =
      6/66, un-anticoagulated controls = 1/60, P = .07). No placebo-controlled trials
      of low-molecular-weight heparins or thrombolytic drugs have been done; therefore,
      their efficacy in VTE depends entirely on randomized comparisons with
      unfractionated heparin. They have not been proven safer or more efficacious than
      unfractionated heparin. Thrombolysis causes more major and fatal bleeds than
      heparin and is no more effective in preventing PE. Diagnosing and treating VTE
      patients in the United States with anticoagulants costs 3.2 dollars to 15.5
      billion dollars per year (1992 dollars). Bleeding and complications of
      angiography cause 1017-3525 deaths annually. CONCLUSION: Anticoagulants have not
      been proven efficacious or safe in VTE. The bleeding risks and other
      complications of anticoagulation are unacceptably high. The use of anticoagulants
      for patients with VTE should be reconsidered.

PMID- 15520629
TI  - Bisphenol A: a scientific evaluation.
AB  - Bisphenol A (BPA) is used in the production of high-volume polycarbonate and
      epoxy resin compounds found in a number of consumer products, including plastic
      bottles and the linings of canned goods. As a result of such applications, very
      small amounts of BPA can migrate into food and drink. In light of reports
      suggesting that low doses of BPA cause estrogenic effects in laboratory animals,
      concerns were raised about the safety of these consumer products, particularly
      plastic bottles used for feeding milk to babies. To evaluate the risk, if any,
      from BPA, investigations were undertaken to more precisely determine human
      exposure levels and more carefully study the validity of the low-dose effects
      reported. On the basis of the most realistic studies of BPA levels in food and
      drink, as well as in human urine, it has been estimated that human exposures,
      including those of children, are very low and range from about .001 to .1 mcg/kg
      body weight (bw)/day. The results of the additional toxicology studies indicated
      that the low-dose effects could not be consistently replicated. In light of this,
      a number of governments and agencies brought together independent expert panels
      to carefully evaluate the toxicologic studies and provide regulatory guidance.
      These panels came to a similar conclusion, namely, that low-dose effects have not
      been demonstrated. They also supported the acceptable daily intake levels
      previously calculated on the basis of high-dose effects shown in laboratory
      animals. Comparing these acceptable intakes with the best exposure estimates
      reveals that human doses of BPA from migration of the compound into food and
      drink are orders of magnitude lower than acceptable daily intakes. Thus, it is
      very unlikely that humans, including infants and young children, are at risk from
      the presence of BPA in consumer products.

PMID- 15520631
TI  - A case report of suspect ginseng allergy.

PMID- 15520630
TI  - Low-dose tiagabine effectiveness in anxiety disorders.
AB  - BACKGROUND: Gamma-aminobutyric acid (GABA), the predominant inhibitory
      neurotransmitter of the central nervous system, is involved in the
      pathophysiology of a wide variety of disorders, including anxiety. Tiagabine
      hydrochloride acts as a selective GABA reuptake inhibitor (SGRI). METHODS AND
      RESULTS: Consecutive patients were offered tiagabine in 1-mg incremental doses
      for the treatment of anxiety, primarily generalized anxiety disorder. Individuals
      failing anxiety treatment with benzodiazepines, selective serotonin reuptake
      inhibitors, and buspirone, and/or with a strong family or personal history of
      substance abuse were allowed trials. The SGRI tiagabine improved anxiety and was
      well tolerated by adult patients with generalized anxiety disorder as well as one
      patient with anxiety secondary to acute antidepressant withdrawal. One
      disinhibition treatment failure is also discussed. CONCLUSION: In acute anxiety
      treatment, very low initial dosing with gradual increases may be sufficient for
      anxiety effects, when compared with the higher doses of tiagabine used in
      epilepsy treatment. Tiagabine may be useful in the treatment of generalized
      anxiety disorder.

PMID- 15520632
TI  - Byline corruption can only be controlled by true stakeholders.

PMID- 15520633
TI  - Through a different lens: a mother's day lament.

PMID- 15520634
TI  - A 46-year-old woman with confusion and syncope.

PMID- 15520635
TI  - Life-threatening acute airway obstruction in achalasia.
AB  - Acute airway obstruction from mega-esophagus is an extremely rare presentation of
      achalasia. We present the case of an 82-year-old woman without previously
      diagnosed achalasia who presented with shortness of breath. Her respiratory
      status deteriorated rapidly, with development of stridor. Prompt nasogastric tube
      placement decompressed the dilated esophagus and relieved airway obstruction.
      This case illustrates an unusual presentation of achalasia and underscores the
      need for emergent life-saving esophageal decompression. Hypotheses regarding the
      mechanism of airway compromise as well as treatment options are reviewed.

PMID- 15520636
TI  - Genetics of colorectal cancer.
AB  - Colorectal cancer (CRC) is the second leading cause of cancer-related mortality
      in the United States. As such, it assumes a significant role in both health
      policy decision-making and scientific research. CRC has been a model for
      investigating the molecular genetics of cancer development and progression; this
      is in part due to the easily detectable, sequential transition of cells from
      normal colonic epithelium to adenoma and then to adenocarcinoma. In addition,
      familial syndromes that predispose to CRC, such as familial adenomatous polyposis
      (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC), have significantly
      contributed to our understanding of the genetic mechanisms underlying CRC
      formation. It is now well recognized that hereditary CRC syndromes are due to
      germline mutations of genes that function as tumor suppressors or, less
      frequently, oncogenes. Accumulation of subsequent mutations in other genes with
      related functions results in the stepwise progression to carcinoma. It is
      important to note that somatic changes in similar genes are involved in the
      formation of sporadic CRC. The identification of these important CRC-related
      genes may help facilitate the early diagnosis, prevention, and treatment of CRC.
      This article reviews the various familial CRC syndromes along with their genetic
      etiology, as well as discusses the principle of genetic testing for these
      conditions.

PMID- 15520637
TI  - Crohn's disease and infections: a complex relationship.

PMID- 15520638
TI  - Endoluminal treatment of GERD--role in contemporary clinical practice.

PMID- 15520639
TI  - An uncommon cause of small bowel obstruction.

PMID- 15520640
TI  - Lentiviral vectors for the central nervous system.

PMID- 15520641
TI  - Conference report--early cancer diagnosis: beating the odds.

PMID- 15520643
TI  - Conference report--gene therapy--quality matters.

PMID- 15520644
TI  - Conference report--gene therapy and lung cancer--no time to wait.

PMID- 15520642
TI  - Telomeres, telomerase, and tumorigenesis--a review.
AB  - Human telomeres function as a protective structure capping both ends of the
      chromosome. They are composed of long, repetitive sequences of TTAGGG, associated
      with a variety of telomere-binding proteins. Telomeres protect the chromosomes
      from end-to-end fusion, recombination, and degradation, all events that can lead
      to cell death. At cell replication, telomeres cannot be completely replicated.
      They are gradually shortened, and when the telomeres reach a critical threshold,
      cell replication is arrested in what is called "replicative senescence." Thus,
      telomeres act as an intrinsic "counting" mechanism of the cell's aging process.
      Telomerase is an enzymatic ribonucleoprotein complex that acts as a reverse
      transcriptase in the elongation of telomeres. Telomerase activity is almost
      absent in somatic cells, but it is detected in embryonic stem cells and in the
      vast majority of tumor cells. Tumor cells, in fact, may contain short and stable
      telomeres that confer immortality to the cancer cells, which are thus able to
      replicate indefinitely. The deregulation of telomeres thus plays an important
      role in the relationship between premature aging syndrome and cancer. This review
      describes the recent advances in the molecular characterization of telomeres, the
      regulation of telomerase

PMID- 15520645
TI  - Conference report--novel therapies for systemic lupus erythematosus?

PMID- 15520646
TI  - Transfusion of RhD-incompatible blood components in RhD-negative blood marrow
      transplant recipients.
AB  - BACKGROUND: Transfusion-dependent bone marrow transplant recipients are routinely
      transfused with ABO group and RhD-compatible blood components. However, because
      of the scarcity of RhD-negative blood components, particularly platelets, a
      policy was developed to transfuse RhD-positive blood components to RhD-negative
      patients during periods of shortage. METHODS: We reviewed the records of 78 RhD
      negative patients with hematologic malignancies who received RhD-negative bone
      marrow and/or peripheral blood stem cells, from June 1995 to August 2000. The
      patients transfused with RhD-incompatible blood components were screened
      periodically for evidence of the development of red blood cell (RBC)
      alloimmunization. RESULTS: Three of 78 patients (4%) developed anti-D antibodies
      after receiving RhD-incompatible platelet transfusions. One of the patients
      developed evidence of anti-RhD antibodies after receiving 42 units of RhD
      positive random donor platelets; the second patient developed such evidence after
      receiving 6 apheresis platelets and 2 infusions of intravenous immunoglobulin G
      (positive for anti-RhD). The third patient received 206 RhD-positive random donor
      platelets and 5 apheresis units. All patients were discharged from the hospital.
      The overall immunization rate was 4%. Six patients received Rh-incompatible
      packed RBCs and showed no evidence of neither anti-RhD nor any other anti-RBC
      antibodies. All 78 patients had received RhD-incompatible platelets throughout
      their engraftment period. CONCLUSION: Transfusion of RhD-positive blood
      components to Rh-negative patients with hematologic cancers, who have received
      RhD-negative bone marrow and/or peripheral blood stem cells, are at low risk of
      developing RhD antibodies. These findings allow for a flexible strategy of blood
      component therapy support for this special patient population during periods of
      shortage.

PMID- 15520647
TI  - Conference report--lupus nephritis: diagnosis, therapy, and outcomes.

PMID- 15520648
TI  - Promotional talks for the pharmaceutical industry.

PMID- 15520649
TI  - Responses from non-US readers to the Webcast video editorial entitled "American
      healthcare is the best in the world if...".

PMID- 15520650
TI  - Responses from US readers to the Webcast video editorial entitled "American
      Healthcare is the best in the world if...".

PMID- 15520651
TI  - Readers' and editors' responses: "American healthcare is the best in the world
      if...".

PMID- 15520652
TI  - Formulary conversion programs: the need for patient-specific risk assessment.

PMID- 15520653
TI  - Patient as gatekeeper: electronic medical records.

PMID- 15520654
TI  - Is politics good for medicine?

PMID- 15520655
TI  - A dissenting voice regarding mandated electronic medical records.

PMID- 15520657
TI  - Medscape's 35th site is cosponsored by the ASCP and dedicated to pathology and
      laboratory medicine.

PMID- 15520658
TI  - MedGenMed delays a policy decision on "registering" clinical trials.

PMID- 15520659
TI  - Should the unpublished results of clinical trials be available to other
      researchers and physicians?

PMID- 15520660
TI  - Is the current standard of medical practice for treating venous thromboembolism
      simply wrong?

PMID- 15520661
TI  - The appropriate medicalization of the management of chemical addiction.

PMID- 15520662
TI  - The 4 phases of a "new" observation-institutionalized racism in healthcare.

PMID- 15520663
TI  - Was there physician complicity in state-sponsored human torture in Guantanamo,
      Iraq, and Afghanistan? An invitation for military physicians to speak out.

PMID- 15520664
TI  - American healthcare is the best in the world if. . .

PMID- 15520665
TI  - What kills people in developed countries?

PMID- 15520666
TI  - Category I CME credit for reading journal articles on Medscape.

PMID- 15520667
TI  - Moving the conflicted issue of authorship forward with data.

PMID- 15520669
TI  - Case 2: an irresistible urge to sleep.

PMID- 15520670
TI  - Amyloid, tau, and cell death in Alzheimer's disease.

PMID- 15520671
TI  - ApoE and Alzheimer's disease--10 years later.

PMID- 15520672
TI  - Weight variations in patients receiving topiramate migraine prophylaxis in a
      tertiary care setting.
AB  - BACKGROUND: Migraine is a highly prevalent chronic neurologic disorder. Frequent
      headache attacks require prophylactic treatment, and side effects are limiting
      prescribing factors among traditional agents for migraine prophylaxis. Beta
      blockers, antidepressants, calcium channel blockers, and anticonvulsants have
      been used since the 1960s, and their efficacy has been demonstrated in several
      controlled studies. However, weight gain commonly occurs with most of these drugs
      and makes adherence to treatment a troublesome issue for many patients.
      Topiramate is a new anticonvulsant with proven efficacy in migraine and other
      conditions, which reportedly confers weight loss in patients receiving doses up
      to 300 mg/day. OBJECTIVE: The aim of this study was to evaluate adherence, weight
      loss, tolerability, and response to topiramate in adult migraineurs receiving
      treatment in a tertiary care center. METHODS: During a 2,5-year period, all
      patients receiving topiramate for migraine were evaluated after 3 months of
      treatment. The parameters evaluated were adherence to treatment, frequency in
      reduction of attacks > 50%, the presence and amount of weight loss, and adverse
      events. RESULTS: Among 175 patients included, 134 (76.6%) adhered to the regimen,
      whereas 4% interrupted before the 3-month evaluation and 19.4% did not return for
      follow-up. Among the 134 patients evaluated, 82 (61.2%) revealed headache
      frequency reduction > 50%; 105 (78.4%) patients experienced weight loss (range 1
      10 kg; average, 3.4 kg). The most frequent side effects were paresthesia (39.6%);
      emotional disturbances, including depression, irritability, and anxiety (17.9%);
      thinking impairment (12.7%); memory disturbances (12.7%); and altered taste
      (11.9%). CONCLUSION: Despite methodologic limitations, we conclude that good
      adherence to topiramate in a "real-world" headache clinic occurred in most of the
      study participants. The majority of patients also experienced weight loss and
      reductions in headache frequency, with an acceptable side-effect profile.

PMID- 15520673
TI  - Prevalence of eating disorders: a comparison of Western and non-Western
      countries.
AB  - OBJECTIVE: To compare the prevalence of eating disorders between Western and non
      Western countries. METHOD: Potential references were identified through an
      English-language literature search using Medline and Medscape articles. RESULTS:
      Prevalence rates in Western countries for anorexia nervosa ranged from 0.1% to
      5.7% in female subjects. Prevalence rates for bulimia nervosa ranged from 0% to
      2.1% in males and from 0.3% to 7.3% in female subjects in Western countries.
      Prevalence rates in non-Western countries for bulimia nervosa ranged from 0.46%
      to 3.2% in female subjects. Studies of eating attitudes indicate abnormal eating
      attitudes in non-Western countries have been gradually increasing. CONCLUSION:
      The prevalence of eating disorders in non-Western countries is lower than that of
      the Western countries but appears to be increasing.

PMID- 15520675
TI  - Sociocultural, environmental, and health challenges facing women and children
      living near the borders between Afghanistan, Iran, and Pakistan (AIP region).
AB  - BACKGROUND: For hundred of years, people in the region encompassed by the
      Afghanistan-Iran-Pakistan borders (AIP region) have been challenged by conflict
      and political and civil instability, mass displacement, human rights abuses,
      drought, and famine. It not surprising that health and quality of life of
      vulnerable groups in this region are among the worst in the world. In general,
      women and children, in particular girls, in the AIP region have had especially
      limited access to healthcare. Women and children have dramatically high rates of
      communicable and non-communicable disease, morbidity, and mortality and a general
      low life expectancy that is rapidly declining. In spite of national and
      international efforts to improve health status of vulnerable populations in this
      region, the key underlying sociocultural determinants of health and disparities
      (ie, gender, language, ethnicity, residential status, and socioeconomic status)
      have not been systematically studied, nor have their relationships to
      environmental challenges been examined. OBJECTIVES: We set out to summarize
      existing information regarding the sociocultural, environmental, and traditional
      determinants of health disparities among different population groups in the AIP
      region; identify gaps in research regarding the communities' needs in the region;
      and highlight factors that must be considered in the design and implementation of
      future health intervention studies in the region. METHODS: We reviewed current
      health literature, official documents, and other information (eg, reports of UN
      agencies) related to the social, cultural, and environmental factors that may
      influence the health outcomes of subpopulations living in the AIP region. We also
      interviewed individuals who had recently worked in this region. RESULTS: Overall,
      the health problems faced by this underdeveloped region can be categorized into
      those resulting from lack of essential supplies and services and those stemming
      from the existing cultural practices in the area. The low health status of the
      people, particularly women and children, in the AIP region is associated with not
      only poor hygiene and lack of water but also limited knowledge and lack of access
      to healthcare services. In addition, cultural, political, and socioenvironmental
      factors play a role, including gender inequality and differences between
      languages spoken locally in the region and those most often used in written
      health education materials. CONCLUSION: Future intervention programs designed for
      this region must use culturally sensitive strategies not only to provide health
      information and health services but also to address the underlying nonmedical
      determinants of health related to gender inequalities.

PMID- 15520677
TI  - Evidence-based medicine needs easy-to-use handheld tools for universal
      utilization.

PMID- 15520678
TI  - Voice recognition and medical transcription.

PMID- 15520679
TI  - An 18-year-old female was admitted to the hospital with uncontrollable writhing
      movements.

PMID- 15520681
TI  - eJIAS and the Bristol-Myers Squibb Foundation's Secure the Future Program.

PMID- 15520682
TI  - eJIAS: Editor's Welcome.

PMID- 15520684
TI  - Dealing with posterior crossbite in young patients.

PMID- 15520685
TI  - Comprehensive clinical evaluation as an outcome assessment for a graduate
      orthodontics program.
AB  - To supplement the American Board of Orthodontics (ABO) objective grading system
      (OGS) for posttreatment dental casts and panoramic radiographs, a comprehensive
      clinical assessment (CCA) method was developed to assess facial form, dental
      esthetics, vertical dimension, arch form, periodontium preservation, root
      resorption, and treatment efficiency. The sum of the CCA and the ABO OGS scores
      was defined as the clinical outcome. To determine a 3-year baseline for treatment
      outcomes in a graduate orthodontic program, the posttreatment records of 521
      consecutive patients were evaluated. The mean ABO OGS score for the entire sample
      was 34.4 points: 32.4, 33.1, and 37.8 points for 1998, 1999, and 2000,
      respectively. The mean CCA score for the entire sample was 4.67 points: 2.96,
      5.13, and 6.15 points for 1998, 1999, and 2000, respectively. Corresponding ABO
      OGS and CCA scores showed a progressive decrease in the quality of finished cases
      that was associated with a treatment time increase from 28.9 to 39.3 months.
      Overall, longer active treatment times resulted in a diminished clinical outcome,
      primarily due to "patient burn-out." Scoring of all finished cases is an
      effective means for determining clinical outcomes. However, the data suggest
      that, in initiating a clinical grading program, it is important to establish a
      multiyear baseline. Patients who are progressing well in treatment tend to be
      finished by the time the current class graduates, and the problem patients are
      transferred. Because long treatment times are associated with diminished clinical
      outcomes, it is often in the best interest of the uncooperative patient to
      terminate treatment rather than extend active mechanics in an attempt to achieve
      a better result.

PMID- 15520686
TI  - Comparing orthodontic treatment outcome between orthodontists and general
      dentists with the ABO index.
AB  - This study used the American Board of Orthodontics (ABO) Objective Grading System
      (ABO index) (ABOI) to compare treatment outcome between patients treated by
      orthodontic specialists (OS) and patients treated by general dentists (GP). The
      sample (n = 196) consisted of 126 dental casts of patients treated by OS and 70
      treated by GPs. All casts were collected in 1997 and 1998 from 10th grade
      students attending high schools in Cuyahoga County, Ohio, and were scored by 1
      operator (Y.A.) calibrated in the use of the ABOI. The mean ABOI score for the OS
      group was 26.0 +/- 11.4 compared with 29.6 +/- 12.8 for the GP group. This
      difference was significant at the P < or = .05 level. Of the 7 components used in
      the ABOI, alignment of teeth was found to be the most significant between groups
      (OS mean = 5.39 +/- 4.37 versus GP mean = 7.8 +/- 5.21, P < or = .0007). In this
      sample, a significantly lower ABOI score was found for patients treated by OS
      compared with patients treated by GP.

PMID- 15520687
TI  - Movement of the lateral and medial poles of the working condyle during
      mastication in patients with unilateral posterior crossbite.
AB  - Patients with unilateral posterior crossbite often show reverse sequential jaw
      movement patterns on the frontal view during mastication on the crossbite side.
      Recent studies show that such patients are prone to suffer from temporomandibular
      joint (TMJ) disc displacement, particularly the lateral portion. The purpose of
      this study was to examine the movement of the lateral and medial poles of the
      working condyle during mastication in such patients. Subjects were 12 consecutive
      patients with unilateral posterior crossbites and without TMJ disc displacements
      and 12 normal subjects. An optoelectronic jaw-tracking system with 6 degrees of
      freedom was used to record the motion of the lateral and medial poles of the
      working condyle during mastication of standardized hard, gummy jelly. The data
      from the first 10 cycles were analyzed. The lateral and medial poles of the
      condyle on the crossbite side moved more in the medial direction and less in the
      lateral direction during mastication in the crossbite patients than the condyle
      in the normal subjects. The lateral pole of the working condyle moved more in the
      posterior and inferior directions and less in the anterior direction than the
      medial pole in all subjects. These results suggest that these condylar movements
      in patients with unilateral posterior crossbites might be related to the
      susceptibility to TMJ disc displacement, particularly the lateral portion.

PMID- 15520688
TI  - Postpubertal assessment of treatment timing for maxillary expansion and
      protraction therapy followed by fixed appliances.
AB  - In this cephalometric investigation, we evaluated the correction of Class III
      malocclusion in subjects who had attained postpubertal skeletal maturity and
      considered whether treatment timing influenced favorable craniofacial
      modifications. All subjects (n = 50) were treated with an initial phase of rapid
      maxillary expansion and protraction facemask therapy, followed by a second phase
      of preadjusted edgewise therapy. The treated sample was divided into an early
      treated group (early mixed or late deciduous dentition, 33 subjects) and a late
      treated group (late mixed dentition, 17 subjects). Mean treatment duration times
      were 7 years 2 months for the early treatment group and 4 years 5 months for the
      late treatment group. The treated patients were matched to untreated controls
      (early control group, 14 subjects; late control group, 10 subjects) on the basis
      of race, sex, mean age at first observation, mean age at second observation, mean
      observation intervals, and type of malocclusion. A modified version of Johnston's
      pitchfork analysis, with additional angular and linear measures for mandibular
      size and shape and for vertical skeletal relationships, was performed. Analysis
      of variance was used to evaluate the difference in means for each cephalometric
      variable in the treated groups compared with the corresponding control groups.
      The findings showed that orthopedic treatment of Class III malocclusion was more
      effective when it was initiated at an early developmental phase of the dentition
      (early mixed or late deciduous) rather than during later stages with respect to
      untreated Class III control groups. Patients treated with rapid maxillary
      expansion and facemask therapy in the late mixed dentition, however, still
      benefited from the treatment, but to a lesser degree. Early treatment produced
      significant favorable postpubertal modifications in both maxillary and mandibular
      structures, whereas late treatment induced only a significant restriction of
      mandibular growth. Significant changes in mandibular size were associated with
      significant changes in mandibular shape only in early treated subjects. The main
      contribution to overall occlusal correction was related to skeletal modifications
      rather than dental changes in both early and late treated groups.

PMID- 15520689
TI  - Skeletal and dental changes in the sagittal, vertical, and transverse dimensions
      after rapid palatal expansion.
AB  - The purpose of this study was to examine the maxillary and mandibular responses
      to rapid palatal expansion (RPE) in all 3 dimensions. Twenty children (average
      age, 11.7 years) who required RPE treatment were included in this study. Pre-
      (T1) and post-RPE (T2) lateral and posteroanterior (PA) cephalograms and study
      models were taken for all patients. For each patient, lateral and PA cephalograms
      at T1 and T2 were traced, and the sagittal, vertical, and transverse measurements
      were made. In addition, on the pre- and postexpansion models, the widths between
      the first premolars, the first molars, and the two acrylic halves of the Haas
      type expander were measured. Results showed that from T1 to T2, the mean SNA
      increased 0.35 degrees (P < .05) and ANB increased 1.00 degrees (P < .05). Both
      the ANS and PNS moved downward (1.30 mm and 1.43 mm, respectively, P < .05), and
      the mandibular plane angle (MP-SN) increased 1.72 degrees (P < .05). The
      maxillary and mandibular incisors did not change significantly after RPE. After
      RPE, the mean increase of maxillary interpremolar width, maxillary intermolar
      width, maxillary width (J-J), nasal width, and interorbital width were found to
      be 110.7%, 104.5%, 30.1%, 23.1%, and 3.3% of the screw expansion, respectively.
      After RPE treatment in children, the maxilla displaced slightly forward and
      downward (P < .05); the mandible rotated downward and backward, and the anterior
      facial height increased significantly (P < .05); and the widths of the maxilla
      and nasal cavity increased significantly (P < .05).

PMID- 15520690
TI  - Spontaneous mandibular arch response after rapid palatal expansion: a long-term
      study on Class I malocclusion.
AB  - The purpose of this study was to investigate the spontaneous mandibular arch
      response to rapid palatal expansion as the sole orthodontic intervention.
      Particular attention was paid to clinically significant effects and long-term
      (mean age, 11.3 years) posttreatment stability in 30 Class I malocclusion
      patients treated during the early and mid mixed dentition. Measurements were made
      directly on 120 dental casts obtained at 4 assessment stages: pre-expansion (A1),
      short-term follow-up (A2), progress (A3), and long-term follow up (A4).
      Comparisons between A1 and A2 showed statistically significant (P < .001)
      increases for intermolar widths (lingual and occlusal values). During the
      transition to the permanent dentition, a significant (P < .001) decrease occurred
      in arch length and arch perimeter. There was a 25% intermolar width (occlusal
      value) decrease from the initial net gain, whereas the lingual values remained
      unchanged. Comparisons between A2 and A4 showed an intermolar width (occlusal
      value) net gain of 50% and a significant (P < .001) decrease for the arch length
      and arch perimeter. There was remarkable stability in intermolar width (lingual
      value) and intercanine width (occlusal value), indicating that the increase in
      the mandibular arch width dimension was in response to the orthopedic effects of
      rapid palatal expansion in the early and mid-mixed dentition and that the
      stability was maintained until adulthood.

PMID- 15520691
TI  - Incremental versus maximum bite advancement during twin-block therapy: a
      randomized controlled clinical trial.
AB  - The aim of this study was to evaluate the effectiveness of incremental and
      maximum bite advancement during treatment of Class II Division 1 malocclusion
      with the Twin-block appliance in the permanent dentition. It was performed at 3
      district general hospitals in the United Kingdom with 4 operators. Two hundred
      three patients, 10-14 years old, were randomized. Control patients had the
      initial bite taken edge-to-edge for appliance construction with a standard Twin
      block. Experimental patients had 2 mm initial bite advancement and subsequent 2
      mm advancements at 6 weekly intervals with a Twin-block appliance incorporating
      advancement screws. Data were collected at the start and the finish of Twin-block
      treatment. The use of incremental advancement of the Twin-block did not confer
      any advantages in terms of process and outcome of the treatment. However, patient
      compliance was influenced by operator and patient age. The duration of treatment
      was influenced by operator and initial overjet. Incremental bite advancement
      produced no advantages over maximum advancement.

PMID- 15520692
TI  - Comparisons of surface roughnesses and sliding resistances of 6 titanium-based or
      TMA-type archwires.
AB  - Six titanium-based or TMA-type archwires (Beta III, Resolve, CNA, TMA, low
      friction ion-implanted TMA or TMAL, and TiMolium) were studied as functions of
      composition, morphology, surface roughness, and sliding mechanics by using a
      scanning electron microscope, an x-ray energy dispersive wavelength analyser, a
      laser specular reflectometer, and a frictional testing machine. In the last
      instrument, all wires were coupled with 0.022-in stainless steel brackets in
      which normal forces were applied by 0.010-in stainless steel ligatures. With
      regard to composition, 5 wires were true beta-titanium alloys having nominal
      compositions of 80% titanium, 10% molybdenum, 6% zirconium, and 4% tin, and 1 was
      an alpha-beta alloy having a nominal composition of 90% titanium, 6% aluminum, 3%
      vanadium, and 1% other. Morphologies varied from surfaces with striations, scale,
      or layers of drawn material that suggested surface steps or fissures. Specular
      reflectance and optical roughness measurements divided the archwires into 2
      groups of 3: Beta III, Resolve, and CNA had an overall mean value of 0.148
      microm; and TMA, TMAL, and TiMolium had a mean overall value of 0.195 microm.
      These roughness measurements and their accompanying details of the compositional
      analyses suggested that there could be as few as 2 vendors manufacturing the 5
      beta-titanium products. For 6 different values of angulation that embraced the
      passive and active regions of sliding, the coefficients of friction varied rather
      narrowly from 0.17 to 0.27 and were independent of surface roughnesses. Although
      these contemporary products are better than their predecessors of over a decade
      ago, other issues might be more important than surface finishes or frictional
      resistances because all products appear fairly comparable.

PMID- 15520693
TI  - Prevalence of malocclusion among adolescents in Ibadan, Nigeria.
AB  - The objective of this study was to determine the prevalence of malocclusion among
      predominantly Yoruba adolescents in Ibadan, Nigeria, and to compare the results
      with those of other authors. The sample for this epidemiological survey comprised
      636 secondary school students, (334 [52.5%] boys and 302 [47.5%] girls), aged 12
      17 years (mean age, 14.72 +/- 1.16 SD). The subjects were randomly selected, and
      none had received previous orthodontic treatment. Occlusal anteroposterior
      relationships were assessed based on the Angle classification. Other variables
      examined were overjet, overbite, crowding, and midline diastema. The results
      showed that about 24% of the subjects had normal occlusions, 50% had Class I
      malocclusions, 14% had Class II malocclusions, and 12% had Class III
      malocclusions. Over 66% had normal overbites, and 14% and 9% had increased and
      reduced values, respectively. Overjet relationship was normal in 66%, increased
      in 16%, and decreased in 8%. Crowding was observed in 20% of the subjects and
      midline diastema in 37%. No statistically significant differences were observed
      for any occlusal variables (P > .05). Class I malocclusion is the most prevalent
      occlusal pattern among these Nigerian students. Different patterns of Class II
      and Class III might be present for the dominant ethnic groups in the country.
      Therefore, a survey of the occlusal pattern in southeastern Nigerians (Ibo ethnic
      group) would appear to be worthwhile.

PMID- 15520694
TI  - Effects of nitric oxide in orthodontic tooth movement in rats.
AB  - The purpose of this study was to evaluate the role of nitric oxide (NO) in
      orthodontic tooth movement in rats. Nomega-nitro-L-arginine methyl ester (L-NAME)
      was used as NO synthase (NOS) inhibitor, and nitro-L-arginine (NLA) was used as
      NOS precursor. Fifty-four Sprague-Dawley rats were divided into 3 equal groups,
      and each group was divided into 3 subgroups. In the first 8 subgroups, 20 g of
      force was applied to the maxillary incisors with a spring. NLA was administered
      in the first 3 subgroups at 10(-4), 10(-5) and 10(-6) mol/L (20 microL/12 hours),
      respectively. L-NAME was administered in the next 3 subgroups with the same
      order, amount, and prescription. The last 3 subgroups were evaluated as control
      groups; in the seventh subgroup, 0.9% NaCl (saline solution) was injected (20
      microL/12 hours). Only the force was administered in the eighth subgroup, and no
      chemical solution or orthodontic force was used in the last subgroup. The rats
      were killed on the fifth day of the experiment. Their premaxillae were dissected,
      and tissue sections were obtained from the coronal, middle, and apical thirds of
      the incisor roots. Multinuclear osteoclasts, Howship's lacunae, capillary
      vascularization, and orthodontic tooth movement were significantly increased in
      the NLA groups compared with the L-NAME and control groups.

PMID- 15520695
TI  - Relationships among nocturnal jaw muscle activities, decreased esophageal pH, and
      sleep positions.
AB  - The purpose of this study was to examine the relationships among nocturnal jaw
      muscle activities, decreased esophageal pH, and sleep positions. Twelve adult
      volunteers, including 4 bruxism patients, participated in this study. Portable pH
      monitoring, electromyography of the temporal muscle, and audio-video recordings
      were conducted during the night in the subjects' homes. Rhythmic masticatory
      muscle activity (RMMA) episodes were observed most frequently, with single short
      burst episodes the second most frequent. The frequencies of RMMA, single short
      burst, and clenching episodes were significantly higher during decreased
      esophageal pH episodes than those during other times. Both the electromyography
      and the decreased esophageal pH episodes were most frequently observed in the
      supine position. These results suggest that most jaw muscle activities, ie, RMMA,
      single short-burst, and clenching episodes, occur in relation to gastroesophageal
      reflux mainly in the supine position.

PMID- 15520696
TI  - Oral appliance titration and nasal resistance in nonapneic subjects.
AB  - Initial mandibular position might be a key factor leading to rapid therapeutic
      outcome in oral appliance therapy for patients with obstructive sleep apnea
      (OSA). The purpose of this study was to investigate the effects of an adjustable
      oral appliance on nasal resistance in 7 nonapneic patients. Upright and supine
      nasal resistance was measured for each subject with an adjustable oral appliance
      in place in 3 mandibular positions: most retruded (MAX0), maximum protrusion
      (MAX100), and 67% of MAX100 (MAX67). A significant decrease in upright and supine
      nasal resistance was observed between MAX0 and MAX67 (P < .01), and between MAX0
      and MAX100 (P < .01), but not between MAX67 and MAX100. In addition, there was a
      positive correlation between the nasal resistance at MAX0 and the nasal
      resistance change from MAX0 to MAX67 (P < .01), indicating that when the mandible
      was advanced from MAX0 to MAX67, the more nasal resistance at MAX0, the greater
      the reduction in nasal resistance at MAX67. These findings suggest that MAX67
      might be indicated as the initial mandibular position and that gradual anterior
      titration of mandibular position beyond MAX67 would give OSA patients rapid
      therapeutic effects by reducing the nasal resistance. Moreover, OSA patients with
      augmented nasal resistance at MAX0 might have a greater reduction in nasal
      resistance in response to MAX67 in oral appliance therapy.

PMID- 15520697
TI  - Acceptance rate of palatal implants: a questionnaire study.
AB  - Implants have gained popularity in orthodontics because they facilitate maximum
      anchorage with minimum patient cooperation. However, some orthodontists avoid
      using implants because psychological aspects of the anchorage systems have not
      been fully reported. In this study, 85 patients who received orthodontic
      treatment with palatal implants in 2 clinics in Austria completed questionnaires.
      The results show that most patients got used to their implants in about 2 weeks;
      95% were satisfied with the treatment, and 86% would recommend the treatment to
      other patients. In addition, 75% of the patients found the orthodontic
      construction between the anchor teeth and the palatal implant less comfortable
      than the implant itself, whereas 7% found the palatal implant less comfortable.
      Approximately 24 months of treatment with the palatal implant is tolerable for
      patients; this is the average orthodontic treatment time.

PMID- 15520698
TI  - Treatment of open bite with microscrew implant anchorage.
AB  - Open bite treatment with microscrew implant anchorage is discussed in relation to
      vertical control of the posterior dentoalvelar dimension. Maxillary microscrew
      implants provided anchorage for intruding the posterior teeth and retracting the
      anterior teeth; mandibular microscrew implants were used to apply intrusion force
      distal to the mandibular first molars to prevent mesial tipping of the posterior
      teeth during space closure. Closing the mandibular plane after intruding the
      maxillary posterior teeth and bodily mesial movement of the mandibular posterior
      teeth contributed to facial profile improvement. The efficacy and potency of
      microscrew implants in open bite treatment are discussed.

PMID- 15520699
TI  - Digital photographs and powerpoint.

PMID- 15520700
TI  - How can I convert my slides to digital images?

PMID- 15520701
TI  - Litigation, legislation, and ethics. Before, during, and after: attributing fault
      to a patient's culpable conduct.

PMID- 15520702
TI  - Out-of-hospital endotracheal intubation and outcome after traumatic brain injury.
AB  - STUDY OBJECTIVE: Previous studies disagree about the effect of out-of-hospital
      endotracheal intubation on traumatic brain injury. This study compares the
      effects of out-of-hospital endotracheal intubation versus emergency department
      (ED) endotracheal intubation on mortality and neurologic and functional outcome
      after severe traumatic brain injury. METHODS: From the 2000 to 2002 Pennsylvania
      Trauma Outcome Study (a registry of all patients treated at trauma centers in the
      Commonwealth of Pennsylvania), adult patients with head/neck Abbreviated Injury
      Scale score of 3 or greater and undergoing out-of-hospital endotracheal
      intubation or ED endotracheal intubation were included. Transferred patients were
      excluded. The primary outcome was death (on hospital discharge). The secondary
      outcomes were neurologic (good versus poor, inferred from discharge to home
      versus long-term care facility) and functional outcome (determined from a
      Functional Impairment Score). The key exposure was endotracheal intubation (out
      of-hospital endotracheal intubation versus ED endotracheal intubation). Using
      multivariate logistic regression, odds estimates for out-of-hospital endotracheal
      intubation were adjusted using age, sex, head/neck Abbreviated Injury Scale
      score, Injury Severity Score, mechanism of injury (penetrating versus blunt),
      admission systolic blood pressure, mode of transport (ground only versus
      helicopter or helicopter + ground), and the use of out-of-hospital neuromuscular
      blocking agents. A propensity score adjustment accounted for the potential
      effects of preexisting conditions, inhospital complications, and social factors
      (drug and alcohol use, race, and insurance coverage). RESULTS: There were 4,098
      patients with head/neck Abbreviated Injury Scale score of 3 or greater who
      received either out-of-hospital endotracheal intubation (n=1,797, 43.9%) or ED
      endotracheal intubation (n=2,301, 56.1%). Adjusted odds of death were higher for
      out-of-hospital endotracheal intubation than ED endotracheal intubation (odds
      ratio [OR] 3.99; 95% confidence interval [CI] 3.21 to 4.93). Out-of-hospital
      endotracheal intubation was associated with an increased adjusted odds of poor
      neurologic outcome (OR 1.61; 95% CI 1.15 to 2.26), moderate or severe functional
      impairment (Functional Impairment Score 6 to 15; OR 1.92; 95% CI 1.40 to 2.64),
      and severe functional impairment (Functional Impairment Score 11 to 15; OR 1.80;
      95% CI 1.29 to 2.52). CONCLUSION: Out-of-hospital endotracheal intubation was
      associated with adverse outcomes after severe traumatic brain injury. The
      implications for current clinical care remain undefined.

PMID- 15520703
TI  - Out-of-hospital endotracheal intubation in traumatic brain injury: outcomes
      research provides us with an unexpected outcome.

PMID- 15520704
TI  - Preprocedural fasting and adverse events in procedural sedation and analgesia in
      a pediatric emergency department: are they related?
AB  - STUDY OBJECTIVE: Fasting time before procedural sedation and analgesia in a
      pediatric emergency department (ED) was recently reported to have no association
      with the incidence of adverse events. This study further investigates
      preprocedural fasting and adverse events. METHODS: Data were analyzed from a
      prospectively generated database comprising consecutive sedation events from June
      1996 to March 2003. Comparisons were made on the incidence of adverse events
      according to length of preprocedural fasting time. RESULTS: Two thousand four
      hundred ninety-seven patients received procedural sedation and analgesia. Four
      hundred twelve patients were excluded for receiving oral or intranasal drugs
      (n=95) or for receiving sedation for bronchoscopy by nonemergency physicians
      (n=317). A total of 2,085 patients received parenteral sedation by emergency
      physicians. Age range was 19 days to 32.1 years (median age 6.7 years); 59.9%
      were male patients. Adverse events observed included desaturations (169 [8.1%]),
      vomiting (156 [7.5%]), apnea (16 [0.8%]), and laryngospasm (3 [0.1%]). Fasting
      time was documented in 1,555 (74.6%) patients. Median fasting time before
      sedation was 5.1 hours (range 5 minutes to 32.5 hours). When the incidence of
      adverse events was compared among patients according to fasting time in hours (0
      to 2, 2 to 4, 4 to 6, 6 to 8, >8, and not documented), no significant difference
      was found. No patients experienced clinically apparent aspiration. CONCLUSION: No
      association was found between preprocedural fasting and the incidence of adverse
      events occurring with procedural sedation and analgesia.

PMID- 15520705
TI  - Clinical practice guideline for emergency department ketamine dissociative
      sedation in children.
AB  - We present an evidence-based clinical practice guideline for the administration
      of the dissociative agent ketamine for emergency department pediatric procedural
      sedation and analgesia. Substantial research in recent years has necessitated
      updates and revisions to the widely disseminated 1990 recommendations. We
      critically discuss indications, contraindications, personnel requirements,
      monitoring, dosing, coadministered medications, recovery issues, and future
      research questions for dissociative sedation.

PMID- 15520706
TI  - Physiologic anterior subluxation: case report of occurrence at C5 to C6 and C6 to
      C7 spinal levels.
AB  - Physiologic anterior subluxation is a phenomenon that is common to the upper
      pediatric cervical spine and characterized by the normal forward displacement of
      one cervical vertebra relative to the subjacent one. Physiologic anterior
      subluxation can be seen in children in the setting of trauma, when it must be
      distinguished from pathologic subluxation. Physiologic anterior subluxation has
      not been reported at lower cervical spinal levels (C 5 to C 6 or C 6 to C 7 ).
      This is a report of physiologic anterior subluxation at C 5 to C 6 and C 6 to C 7
      spinal levels distinguished from pathologic subluxation in a 9-year-old child
      evaluated in the acute setting after cervical spine injury.

PMID- 15520707
TI  - Out-of-hospital delays in patients with acute stroke.
AB  - STUDY OBJECTIVE: We determine the interval between stroke symptom onset and time
      to emergency department (ED) arrival and factors associated with delays in
      presentation. METHODS: All patients with acute stroke presenting at 4 hospitals
      in a metropolitan area and consenting to an interview were prospectively included
      over a 12-month period, excluding patients with presentation greater than 7 days
      after onset of symptoms and discharge or death within 24 hours after ED arrival.
      Initially, National Institutes of Health Stroke Scale and times of symptom onset
      and of ED arrival were registered by a neurologist. Sociodemographic factors and
      data about the course of events were obtained by standardized interview conducted
      with patients or proxies. In a multivariable analysis, an extended Cox
      proportional hazards model was used, and hazard ratios were determined. RESULTS:
      Primary analyses were performed for 558 interviewed patients (mean age 66.8+/
      13.5 years, 45% female patients) with confirmed stroke; 452 (81%) patients had a
      known onset of symptoms. Median interval between symptom onset and ED arrival was
      151 minutes (range 5 to 9,590 minutes). Transport by emergency medical services
      (adjusted hazard ratio 0.28 [95% confidence interval (CI) 0.19 to 0.41]),
      increasing age (hazard ratio 0.99 [95% CI 0.98 to 0.99]), greater stroke severity
      (National Institutes of Health Stroke Scale score; hazard ratio 0.93 [95% CI 0.90
      to 0.96]), having transient ischemic attack rather than persistent symptoms
      (hazard ratio 0.32 [95% CI 0.22 to 0.46]) and symptoms considered urgent (hazard
      ratio 0.68 [95% CI 0.55 to 0.84]) were the factors most strongly associated with
      a shorter out-of-hospital interval. CONCLUSION: There are considerable delays
      between stroke symptom onset and ED arrival. Programs to improve awareness of
      patients with stroke to seek medical help immediately may reduce unnecessary
      delays to ED arrival.

PMID- 15520708
TI  - Emergency department presentation of bilateral carotid artery dissections in a
      postpartum patient.
AB  - Spontaneous unilateral postpartum carotid arterial dissection is a rarely
      reported event. This is the first reported case of bilateral carotid artery
      dissection. A 35-year-old gravida 4, para 3 woman presented to our emergency
      department with complaint of headache for 3 days. Medical history included
      delivery of a full-term infant by cesarean section 9 days before presentation
      because of arrest of descent after 3 hours of pushing. Symptoms were later
      attributed to a parietal lobe cerebral vascular accident and bilateral internal
      carotid artery dissection. Physicians should consider the possibility of arterial
      dissection in any postpartum patient with unremitting headache when evaluation of
      typical causes fails to lead to a diagnosis. Appropriate diagnostic evaluation
      and treatment should be actively pursued in this population.

PMID- 15520709
TI  - Impact of a rapid rule-out protocol for pulmonary embolism on the rate of
      screening, missed cases, and pulmonary vascular imaging in an urban US emergency
      department.
AB  - STUDY OBJECTIVE: This study tests the hypothesis that implementation of a point
      of-care emergency department (ED) protocol to rule out pulmonary embolism would
      increase the rate of evaluation without increasing the rate of pulmonary vascular
      imaging or ED length of stay and that less than 1.0% of patients with a negative
      protocol would have an adverse outcome. METHODS: A baseline study was conducted
      on patients with suspected pulmonary embolism at an urban ED to establish
      baseline measurements performed when only pulmonary vascular imaging was
      available to rule out pulmonary embolism. The intervention protocol used pretest
      probability assessment, a whole-blood d -dimer assay, and an alveolar dead-space
      measurement to rule out pulmonary embolism. The main outcomes were diagnosis of
      venous thromboembolism or sudden unexpected death within 90 days. RESULTS: During
      baseline, 453 of 61,322 patients (0.74%; 95% confidence interval [CI] 0.67% to
      0.81%) underwent pulmonary vascular imaging, and 8% (95% CI 6% to 11%) of scan
      results were positive; 1.20% (95% CI 0.39% to 2.78%) of untreated discharged
      patients were anticoagulated for venous thromboembolism or died unexpectedly
      within 90 days. The median length of stay was 385 minutes. After intervention,
      1,460 of 102,848 patients (1.42%; 95% CI 1.35% to 1.49%) were evaluated for
      pulmonary embolism. Seven hundred fifty-two patients had a negative protocol and
      5 of 752 (0.66%; 95% CI 0.20% to 1.54%) had venous thromboembolism within 90
      days, none with unexpected death. After intervention, the rate of pulmonary
      vascular imaging tended to decrease (0.64%; 95% CI 0.59% to 0.69%), and more
      scans (11%; 95% CI 9% to 14%) were read as positive; the length of stay decreased
      to 297 minutes. CONCLUSION: A point-of-care pulmonary embolism rule-out protocol
      doubled the rate of screening for pulmonary embolism in the ED, had a false
      negative rate of less than 1.0%, did not increase the pulmonary vascular imaging
      rate, and decreased length of stay.

PMID- 15520710
TI  - Prospective validation of Wells Criteria in the evaluation of patients with
      suspected pulmonary embolism.
AB  - STUDY OBJECTIVE: The literature suggests that the d -dimer is useful in patients
      suspected of having pulmonary embolism and who have a low pretest probability of
      disease. A previously defined clinical decision rule, the Wells Criteria, may
      provide a reliable and reproducible means of determining this pretest
      probability. We evaluate the interrater agreement and external validity of Wells
      Criteria in determining pretest probability in patients suspected of having
      pulmonary embolism. METHODS: This was a prospective observational study. Trained
      research assistants enrolled patients during 120 random 8-hour shifts. Patients
      who underwent imaging for pulmonary embolism after a medical history, physical
      examination, and chest radiograph were enrolled. Treating providers and research
      assistants determined pretest probability according to Wells Criteria in a
      blinded fashion. Two d -dimer assays were run. Three-month follow-up for the
      diagnosis of pulmonary embolism was performed. Interrater agreement tables were
      created. kappa Values, sensitivities, and specificities were determined. RESULTS:
      Of the 153 eligible patients, 3 patients were missed, 16 patients declined, and
      134 (88%) patients were enrolled. Sixteen (12%) patients were diagnosed with
      pulmonary embolism. The kappa values for Wells Criteria were 0.54 and 0.72 for
      the trichotomized and dichotomized scorings, respectively. When Wells Criteria
      were trichotomized into low pretest probability (n=59, 44%), moderate pretest
      probability (n=61, 46%), or high pretest probability (n=14, 10%), the pulmonary
      embolism prevalence was 2%, 15%, and 43%, respectively. When Wells Criteria were
      dichotomized into pulmonary embolism-unlikely (n=88, 66%) or pulmonary embolism
      likely (n=46, 34%), the prevalence was 3% and 28%, respectively. The
      immunoturbidimetric and rapid enzyme-linked immunosorbent assay d -dimer assays
      had similar sensitivities (94%) and specificities (45% versus 46%). CONCLUSION:
      Wells Criteria have a moderate to substantial interrater agreement and reliably
      risk stratify pretest probability in patients with suspected pulmonary embolism.

PMID- 15520711
TI  - Heparin-induced thrombocytopenia in the emergency department.
AB  - We describe 3 patients who presented to the emergency department (ED) with
      stroke, deep venous thrombosis, or pulmonary embolism and renal failure after
      undergoing cardiac surgery 7 to 17 days earlier. Their onset of thrombosis after
      previous heparin exposure was temporally plausible for complications of heparin
      induced thrombocytopenia, an immune-mediated thrombotic disorder triggered by
      heparin. The patients had normal platelet counts at presentation, yet each had
      circulating heparin-induced thrombocytopenia antibodies that were ultimately
      confirmed. Two patients had heparin reexposure in the ED, 1 of whom developed
      thrombocytopenia with new thrombosis and died. Alternative parenteral
      anticoagulation prevented further thrombosis in 2 patients. Because heparin use
      can be catastrophic in patients with heparin-induced thrombocytopenia, physicians
      should be vigilant in suspecting heparin-induced thrombocytopenia in patients
      with thrombosis after recent hospitalization or heparin exposure. Alternative
      anticoagulants are available for these at-risk patients.

PMID- 15520712
TI  - The Australasian Triage Scale: examining emergency department nurses' performance
      using computer and paper scenarios.
AB  - STUDY OBJECTIVE: The purpose of this study is to examine emergency nurses'
      performance using triage scenarios characterized by type of patient population
      (adult versus pediatric) and mode of delivery (paper versus computer). METHODS: A
      combination of paper-based (script alone) and computer-based (script plus still
      photographs) triage scenarios were used. Of the 28 scenarios used, half were
      written and half were computer based. Within each subgroup, there were 7 adult
      and 7 pediatric scenarios. Participants were asked to allocate an Australasian
      Triage Scale category for each triage scenario. RESULTS: One hundred sixty-seven
      participants completed a total of 2,349 adult scenarios, and 161 participants
      completed 2,265 pediatric scenarios. Sixty-one percent of the triage decisions
      made by the nurses were "expected" triage decisions, 18% were "undertriage,"
      decisions, and 21% were "overtriage" decisions. Nurse triage allocation decisions
      for the scenarios containing still photographs delivered by computer demonstrated
      a higher average agreement percentage of 66.2% (kappa=0.56; tau b =0.77; P
      <.0001) compared with the average agreement percentage of 55.4% (kappa=0.42; tau
      b =0.75; P <.0001) using paper-based (text-only) scenarios. CONCLUSION: The mode
      of delivery appeared to have an effect on the nurses' triage performance. It is
      unclear whether the use of simple still photographs used in the computer mode of
      delivery resulted in a higher incidence of expected triage decisions and, thus,
      improved performance. The use of cues such as photographs and video footage to
      enhance the fidelity of triage scenarios may be useful not only for the education
      of triage nurses but also the conduct of research into triage decisionmaking.
      However, further exploration and research in this area are warranted.

PMID- 15520713
TI  - Emergency department triage: why we need a research agenda.

PMID- 15520714
TI  - What constitutes the standard of care?

PMID- 15520715
TI  - Update on emerging infections: news from the Centers for Disease Control and
      Prevention. Preliminary FoodNet data on the incidence of infection with pathogens
      transmitted commonly through food--selected sites, United States, 2003.

PMID- 15520716
TI  - Evidence-based emergency medicine/systematic review abstract. Should children
      with otitis media be treated with antibiotics?

PMID- 15520718
TI  - Love, riots, and friendship: My ED.

PMID- 15520717
TI  - Evidence-based emergency medicine/systematic review abstract. Use of
      anticoagulants in acute ischemic stroke.

PMID- 15520719
TI  - Images in emergency medicine. Cavernous sinus thrombosis.

PMID- 15520721
TI  - Flying amid wires: detection and survival, part II.

PMID- 15520723
TI  - Pediatric firearm injuries.

PMID- 15520730
TI  - Serving the twin states for 10 years: The Dartmouth-Hitchcock Advanced Response
      Team.

PMID- 15520731
TI  - Fatal vapor: how weather kills.

PMID- 15520732
TI  - UT LIFESTAR-rising: to new heights for 20 years.

PMID- 15520733
TI  - Using net present value as a decision-making tool.

PMID- 15520734
TI  - Shift length and on-duty rest patterns in rotor-wing air medical programs.
AB  - INTRODUCTION: Air medical teams provide around-the-clock critical care, a pattern
      at risk of inducing performance-altering fatigue from circadian disruption and
      sleep deprivation. Safety is an essential issue in the air medical industry, but
      little data are available on shift length and on-duty rest practices. We report
      the results of a survey concerning those practices and analyze the relationships
      to crew duty practices by program model (hospital-operated, vendor-operated,
      independent, or public safety), base location, flight volume, and job
      requirements. METHODS: A survey was mailed to 182 Association of Air Medical
      Services-member rotor-wing air medical programs in the United States that
      complete scene flights with a flight nurse. One-hundred-twenty-nine programs
      (70.9%) returned anonymous surveys, all of which were used for data analysis.
      Results were analyzed with descriptive and nonparametric statistics. RESULTS: All
      pilots work shifts between 10 and 14 hours. For medical team members the shift
      distribution is: </= 8 hours, 0.4%; 9 to 12 hours, 44.2%; 12 to 16 hours, 7.0%;
      17 to 24 hours, 45%; > 24 hours, 3.5%. An independent association exists between
      shift length greater than 12 hours and each of the following: flight volume per
      aircraft under 731 flights/year, program model other than hospital operated, and
      nonhospital base (Fisher's exact test with Bonferroni correction, P < .01 for
      each). All pilots are allowed on-duty rest on both day and night shifts. On-duty
      rest is permitted for 67.4% of medical team members: 18.2% only at night, and
      49.2% at any time of day. The presence of any period of on-duty crew rest is
      significantly associated with nonhospital base, program model other than hospital
      operated, and shift length exceeding 12 hours (Fisher's exact test with
      Bonferroni correction, P < .01 for each). The presence of a nonflight clinical
      assignment while on flight duty is associated with a prohibition against on-duty
      rest (Fisher's exact test with Bonferroni correction, P < .05). CONCLUSION:
      Notable differences arose between on-duty work and rest patterns for pilots and
      medical team members. Medical team members generally work longer shifts than
      pilots do, with shifts exceeding 12 hours as the most common staffing pattern.
      Medical team members also have less access to on-duty rest than do pilots.
      Traditional hospital-operated programs are more likely to use shorter shifts and
      prohibit on-duty rest for the medical teams, whereas vendor-operated,
      independent, or public safety programs are more likely to use longer shifts and
      permit on-duty rest. As the industry works toward a unified approach to
      mitigating the impact of fatigue on safe operation, variable practices based on
      job description and program style may be a factor.

PMID- 15520747
TI  - Medicaid...the impending storm.

PMID- 15520748
TI  - Low superior vena cava flow during the first postnatal day and neurodevelopment
      in preterm neonates.

PMID- 15520749
TI  - Immature white matter lesions in the premature infant.

PMID- 15520750
TI  - The milk of human constipation.

PMID- 15520751
TI  - Gall bladder abnormalities in children with sickle cell disease: management with
      laparoscopic cholecystectomy.

PMID- 15520752
TI  - An approach to target joint bleeding in hemophilia: prophylaxis for all or
      individualized treatment?

PMID- 15520753
TI  - Acute hospital-induced hyponatremia in children: a physiologic approach.

PMID- 15520755
TI  - Low superior vena cava flow and neurodevelopment at 3 years in very preterm
      infants.
AB  - OBJECTIVES: Low superior vena cava (SVC) flow is common in the first hours after
      very preterm birth and has a strong association with subsequent
      periventricular/intraventricular hemorrhage. We report the neurodevelopmental
      outcome at 3 years of age of very preterm babies who had serial echocardiographic
      studies, including measures of SVC flow, during the first 48 hours after birth.
      STUDY DESIGN: A prospective observational study was performed on a cohort of 126
      babies (<30 weeks), 103 of whom survived to discharge. Neurodevelopmental follow
      up data, which included abnormal developmental quotient, abnormal motor score,
      and cerebral palsy, were available for 93% of this cohort at 3 years of age.
      Relations between 3-year outcome and early hemodynamic measures and clinical
      parameters were explored. RESULTS: After controlling for confounding variables,
      average SVC flow over the first 24 hours of life was significantly associated
      with the primary outcome of death or survival with any disability (P=.004) and
      with the secondary outcome of abnormal developmental quotient (P = .006). A
      greater number of low SVC flow readings during the first 24 hours was
      significantly related to death and adverse developmental outcome, but the
      individual lowest SVC flow was not, suggesting the importance of duration of low
      SVC flow. After adjustment, there was no significant association between average
      mean blood pressure over the first 24 hours and abnormal developmental outcome,
      whereas the proportion of mean blood pressure readings less than the gestational
      age showed a trend toward an association with death and any disability.
      CONCLUSIONS: Low early postnatal blood flow to the upper body and brain may be
      one factor in the causal pathway of impaired preterm neurodevelopmental outcome.

PMID- 15520756
TI  - Trends in severe brain injury and neurodevelopmental outcome in premature newborn
      infants: the role of cystic periventricular leukomalacia.
AB  - OBJECTIVES: To determine if the incidence of sonographically detected cystic
      periventricular leukomalacia (PVL) and periventricular hemorrhagic infarction
      (PVHI) have changed over the past decade and to determine if a decline in cystic
      PVL was associated with a change in neurodevelopmental outcome. STUDY DESIGN:
      Premature newborn infants admitted to our intensive care nursery from 1992 to
      2002 were identified in a comprehensive nursery database. Premature newborn
      infants had routine neurosonography by means of a standardized protocol. Infants
      weighing < or =1500 g at birth surviving to nursery discharge were enrolled in a
      nursery follow-up clinic. RESULTS: Adjusting for gestational age, there was a
      significant decrease in cystic PVL from 1992 to 2002 (P=.003) without a
      concurrent decrease in PVHI (P=0.5). Cystic PVL and PVHI accounted for only 9 of
      the 28 cases of cerebral palsy and 12 of 90 cases of abnormal Developmental
      Scores in infants weighing <1500 g at birth. The decline in cystic PVL was not
      associated with improved developmental outcome from 1992 to 2002. CONCLUSIONS:
      The incidence of cystic PVL declined significantly from 1992 to 2002 at our
      center. Cystic PVL was detected by ultrasound in a minority of infants with
      abnormal neurodevelopmental outcome, indicating that other forms of cerebral
      injury account for the majority of abnormal neurodevelopmental outcomes in
      premature newborn infants.

PMID- 15520757
TI  - Feeding effects on growth during infancy.
AB  - OBJECTIVE: To examine the effects of formula, other milks, other liquids,
      cereals, and other solid foods on growth during infancy. STUDY DESIGN:
      Observational cohort study nested within a large (n=17,046), cluster-randomized
      trial. We compared growth [weight-for-age, length-for-age, and weight-for-length
      z scores (WAZ, LAZ, WLZ) and head circumference (HC)] during the intervals 1 to
      3, 3 to 6, 6 to 9, and 9 to 12 months, using hierarchical multivariate regression
      to control for size at the beginning of each interval, maternal education,
      geographic region, and urban versus rural location. RESULTS: Mixed BF and
      formula/other milk were associated with significantly higher (versus breast milk
      only) LAZ at 1 to 3 months (+0.038 and +0.047, respectively). In the 3- to 6
      month interval, mixed BF and formula/other milk led to significantly higher WAZ
      (+0.125 and +0.139) and LAZ (+0.081 and +0.075), whereas cereal intake was
      associated with large and highly significant reductions in both measures (-0.293
      and -0.240) and in HC (-0.291 cm). Mixed BF and formula/other milk continued to
      have positive albeit smaller associations with WAZ and LAZ in the 6- to 9-month
      and 9- to 12-month intervals. CONCLUSIONS: Our results confirm the growth
      accelerating effects of formula and other milks (versus breast milk) on weight
      and length gain throughout infancy, with a dose-response gradient and largest
      associations observed at 3 to 6 months.

PMID- 15520758
TI  - Lymphoid nodular hyperplasia and cow's milk hypersensitivity in children with
      chronic constipation.
AB  - OBJECTIVE: To investigate the incidence of cow's milk allergy as evidenced by
      milk challenge and the findings of endoscopic and immunohistochemical
      examinations in children with chronic and refractory constipation. STUDY DESIGN:
      Thirty-five study subjects (mean age, 8.3 +/- 3.3 years; range, 3-15 years; 17
      girls) and 15 control subjects (mean age, 11.7 +/- 3.2 years; range, 2-15 years;
      9 girls) were studied by colonoscopy and a 4-week cow's milk elimination and
      challenge. RESULTS: Lymphoid nodular hyperplasia was the most prominent
      endoscopic finding in half of the subjects (46%), mostly occurring patchily in
      the transverse colon. Histologic findings other than lymphoid accumulation and
      mildly increased density of eosinophils were few. During the milk elimination and
      with supportive medication, 83% of subjects remitted. Constipation and/or other
      gastrointestinal or skin symptoms relapsed only in one third (34%) during the
      cow's milk challenge, these having significantly higher densities of
      intraepithelial gammadelta + T cells ( P <.001) in the biopsy samples of the
      terminal ileum as compared with the control subjects. CONCLUSIONS: We were able
      to find formal evidence for the presence of cow's milk allergy in children with
      chronic constipation.

PMID- 15520759
TI  - Effect of probiotics on gastrointestinal symptoms and small intestinal
      permeability in children with atopic dermatitis.
AB  - OBJECTIVE: To determine whether probiotic lactobacilli may alleviate small
      intestinal inflammation and strengthen the intestinal barrier function in
      children with atopic dermatitis. STUDY DESIGN: In a double-blinded, placebo
      controlled, cross-over study, probiotic lactobacilli (Lactobacillus rhamnosus
      19070-2 and L reuteri DSM 12246) were administered for 6 weeks to 41 children
      with moderate and severe atopic dermatitis. Gastrointestinal symptoms were
      registered before and during treatment and small intestinal permeability was
      measured by the lactulose-mannitol test. RESULTS: During Lactobacillus
      supplementation, there was a significant decrease in the frequency of
      gastrointestinal symptoms (39% during the placebo period versus 10% during active
      treatment, P=.002). There was a positive association between the lactulose to
      mannitol ratio and the severity of the eczema (r=0.61, P=.02 after placebo and
      r=0.53, P=.05 after active treatment). After probiotic treatment, the lactulose
      to mannitol ratio was lower (0.073) than after placebo (0.110, P=.001).
      CONCLUSIONS: Impairment of the intestinal mucosal barrier appears to be involved
      in the pathogenesis of atopic dermatitis. The study suggests that probiotic
      supplementation may stabilize the intestinal barrier function and decrease
      gastrointestinal symptoms in children with atopic dermatitis.

PMID- 15520760
TI  - Outcomes for children with gallbladder abnormalities and sickle cell disease.
AB  - OBJECTIVE: To determine whether elective cholecystectomy is justifiable in
      children with sickle cell disease (SCD), gallbladder abnormalities, and minimal
      clinical symptoms. STUDY DESIGN: A retrospective review comparing clinical
      presentations and abdominal ultrasound results with outcomes in 146 children with
      SCD. RESULTS: Ultrasound examination showed sludge or stones in 83 of 146
      children (57%). This was found during a diagnostic ultrasound in 59 patients
      (71%) and during a screening ultrasound in 24 asymptomatic patients (29%). Fifty
      four (65%) children with a positive ultrasound underwent cholecystectomy; 13 of
      these were initially asymptomatic patients who had subsequent development of
      clinical symptoms. Of the patients with cholecystectomy, 93% had histopathologic
      evidence of cholecystitis. Perioperative complications were rare, and there were
      no episodes of postoperative acute chest syndrome. Children who underwent
      elective surgery had an average 12-days-shorter overall hospital stay than those
      who underwent emergent surgery (4 vs 16 days, P <.001). CONCLUSIONS: Elective
      laparoscopic cholecystectomy may be safely performed in children with SCD.
      Surgery should be strongly considered at the time of gallstone diagnosis before
      symptoms or complications develop. Histopathologic chronic cholecystitis does not
      correlate with clinical symptoms.

PMID- 15520761
TI  - Low vitamin D status in children with sickle cell disease.
AB  - OBJECTIVES: To examine vitamin D status in children with sickle cell disease
      (SCD)-SS and its relation to season and dietary intake. STUDY DESIGN: Growth,
      dietary intake, 25-hydroxyvitamin D (25-OHD), and parathyroid hormone levels were
      measured. Children with low and normal vitamin D status were compared. Low
      vitamin D status was defined as a serum concentration of 25-OHD <27.5 nmol/L.
      Serum 25-OHD and parathyroid hormone levels were compared among children with SCD
      SS and healthy children. RESULTS: Children with SCD-SS (n=65), 5 to 18 years of
      age, were evaluated. Mean (+/-SD) serum 25-OHD concentration was 25.5 +/- 12.8
      nmol/L; 65% of subjects had low vitamin D status. Low vitamin D prevalence was
      highest during spring (100%). Children with SCD-SS were at higher risk for low
      vitamin D status than healthy children. Vitamin D intake was lower in subjects
      with SCD-SS and low vitamin D than those with normal serum vitamin D status (P
      <.05). CONCLUSIONS: Low serum vitamin D status was highly prevalent in black
      children with SCD-SS. Vitamin D status was associated with season and dietary
      intake.

PMID- 15520762
TI  - Clinical and cost implications of target joints in Canadian boys with severe
      hemophilia A.
AB  - OBJECTIVE: To compare target joint-associated costs incurred by boys with severe
      hemophilia A 1 year before and 1 year after development of a target joint (pre
      TJ, post-TJ). STUDY DESIGN: Resource utilization data were extracted
      retrospectively from medical and hemophilia clinic charts and patient diaries for
      16 boys attending the Hospital for Sick Children (HSC)'s comprehensive care
      hemophilia program. Resources examined included drugs, medical care,
      hospitalization, laboratory tests, therapies, and transfusions received. All
      costs were figured using standard price lists and were discounted using an annual
      rate of 3%. RESULTS: Fifteen of the 16 boys developed at least one target joint,
      defined as three bleeds into any single joint within a consecutive 3-month
      period, at an average age of 54 months (range, 15-94 months), with ankles being
      most often affected, followed by elbows and knees (46% vs 28% and 23%,
      respectively). The total cost of treating a boy with on-demand Factor VIII
      (FVIII) increased by 119% after development of a target joint, from $20,091 (in
      2002 Canadian dollars [$CDN]) in the year before to $43,890 in the year after
      target joint development. Factor VIII use accounted for 87% of the total cost in
      the year before target joint development and 93% in the year after. CONCLUSIONS:
      This study identified substantial increased costs of care associated with target
      joint development. This finding provides further support for more aggressive
      treatment aimed at reducing target joints-either more aggressive treatment of
      joint bleeds or institution of primary prophylactic therapy at an early age.

PMID- 15520764
TI  - Characteristics of children who have full or incomplete fetal alcohol syndrome.
AB  - OBJECTIVE: To describe the clinical features and hospitalization rates of
      American Indian children with full or incomplete fetal alcohol syndrome (FAS).
      STUDY DESIGN: Two retrospective case-control studies were conducted of Northern
      Plains American Indian children with presumed FAS identified from 1981 to 1993 by
      using the International Classification of Diseases, Ninth Revision, Clinical
      Modification (ICD-9-CM), code 760.71. Children who had full or incomplete FAS
      were compared with each other and with children who did not have FAS. RESULTS:
      Compared with the control children, the 43 children with FAS and the 35 children
      with incomplete FAS had more facial dysmorphology, growth deficiency, central
      nervous system dysfunction, and muscular problems and were hospitalized more
      frequently with otitis media, pneumonia, FAS, dehydration, and anemia. Case
      children were hospitalized more days than were control children. Case children
      were removed from their homes and placed in foster care more often than were
      control children. CONCLUSIONS: Children with full or incomplete FAS had many
      health, learning, and social needs. Health care providers and community programs
      should identify the needs of these children and offer optimal services to meet
      those needs.

PMID- 15520765
TI  - Oxygen saturation as a predictor of prolonged, frequent bronchodilator therapy in
      children with acute asthma.
AB  - OBJECTIVES: To examine if the initial oxygen saturation (SaO2) in the Emergency
      Department is a useful predictor of prolonged frequent bronchodilator therapy
      (FBT) in children with acute asthma. STUDY DESIGN: Prospective cohort study of
      273 children, 1 to 17 years of age, requiring systemic corticosteroids. Patients
      were categorized as needing FBT for >4 hours (n=166) versus >4 hours (n=107) and
      >12 hours (n=79) versus >12 hours (n=194). Multiple logistic regression
      determined the association between SaO2 and these outcomes. RESULTS: Baseline
      SaO2 remains a significant independent predictor of FBT for >4 hours (OR=0.81)
      and >12 hours (OR=0.84); 91% of patients with SaO2 of 90% to 91% had FBT >4 hours
      and 80% of patients with SaO2 of < or =89% had FBT >12 hours. Children with SaO2
      of < or =91% are 14.7 and 12.0 times more likely to require FBT for >4 hours and
      >12 hours, respectively, than those with SaO2 of 98% to 100%. The interval
      likelihood ratios for FBT >4 hours were 12.3 for SaO2 of < or =89%, 6.5 for 90%
      to 91%, but only 1.8 for 92% to 93%. The likelihood ratios for FBT >12 hours
      decreased from 9.8 for SaO2 of < or =89% to 3.5 for SaO2 of 90% to 91%.
      CONCLUSIONS: SaO2 is a useful predictor of FBT >4 hours if it is < or =91% and of
      FBT >12 hours if it is < or =89%.

PMID- 15520767
TI  - Expanding the phenotype of alveolar capillary dysplasia (ACD).
AB  - OBJECTIVES: To define the phenotype of congenital alveolar capillary dysplasia
      (ACD) as a first step toward mapping the responsible gene(s). STUDY DESIGN:
      Analysis of pathology reports and microscopic slides of 23 subjects with ACD and
      sequence analysis of two candidate genes. RESULTS: Our review of the pre- and
      postmortem records delineates both the natural history of this condition and the
      associated anomalies. Our collection of families corroborates the likely
      autosomal recessive nature of this condition in some families and provides
      additional data for genetic and prenatal counseling. Anomalies of many organ
      systems were detected either in the prenatal period or during the hospital
      course. However, some major anomalies were not detected until postmortem
      examination. Left-right asymmetry and gastrointestinal malrotation emerge as
      important, previously recognized but underappreciated phenotypic features of ACD.
      Finally, we used sequence analysis to exclude mutations in the coding region of
      two candidate genes, bone morphogenetic protein type II receptor (BMPR2) and
      endothelial monocyte-activating polypeptide II (EMAP II), as candidates for ACD.
      CONCLUSIONS: Understanding the clinical spectrum of ACD and the cloning of an
      "ACD gene" both have implications for counseling, for prenatal testing, and for
      understanding the molecular pathophysiology of ACD and other organ malformations
      that are associated with this condition.

PMID- 15520768
TI  - Television, video, and computer game usage in children under 11 years of age.
AB  - OBJECTIVE: To conduct a population-based survey of television and other media
      usage in young children to determine (1) total media usage; (2) the proportion of
      children who have televisions in their bedrooms and who eat breakfast or dinner
      in front of the television; and (3) predictors of parental concern about the
      amount of television their child watches. STUDY DESIGN: Telephone survey
      administered to 1454 parents of children <11 years old derived from a diverse
      clinic population. RESULTS: The mean age of the index child was 5.05 years. Mean
      daily reported child media use was as follows: television (1.45 hours; SD, 1.5);
      videos (1.1 hours; SD, 1.30); and computer games (0.54 hours; SD, 0.96). Thirty
      percent of parents reported that their child ate breakfast or dinner in front of
      the television in the past week, and 22% were concerned about the amount of
      television that their child watched. In multivariate linear regression, eating
      breakfast or dinner in front of the television in the past week was associated
      with increased hours of television viewing (0.38 hours [0.21, 0.54]) and video
      (0.19 hours [0.04, 0.34]). Having a television in a child's bedroom was
      associated with increased hours of television (0.25 hours [0.07, 0.43]), video
      viewing (0.31 hours [0.16, 0.47]), and computer games (0.21 hours [0.10, 0.32]).
      In general, higher parental education was associated with decreased hours of
      television and video but not computer games. Older children were 2 to 3 times
      more likely than younger children to have a television in their bedroom and to
      have eaten a meal in front of it in the past week. More educated parents were
      less likely to report that their child had a television in their bedroom and more
      likely to be concerned about the amount of television their child viewed.
      CONCLUSIONS: Combined video and computer game usage exceeded television usage.
      Both children of low- and high-income parents are at risk for certain behaviors
      associated with television usage. Parents whose children watched more television
      were more likely to be concerned about the amount of television their child
      viewed.

PMID- 15520769
TI  - Peripheral inflammatory and fibrinolytic markers in adolescents with growth
      hormone deficiency: relation to postprandial dyslipidemia.
AB  - OBJECTIVE: To determine whether peripheral inflammatory and fibrinolytic markers
      are elevated in growth hormone-deficient (GHD) adolescents and associated with
      increased postprandial lipoproteins. STUDY DESIGN: Fifteen GHD children on GH
      treatment with a chronologic age of 12.7 +/- 2.5 years and 10 untreated GHD
      adolescents with a chronologic age of 13.0 +/- 2.6 years were studied.
      Triglycerides (TG), C-reactive protein (CRP), fibrinogen, interleukin 6 (IL-6),
      and tumor necrosis factor alpha (TNF-alpha) were measured in the fasting state
      and 4 hours after ingesting a high-fat meal; 15 healthy adolescents served as
      controls. RESULTS: Fasting and postprandial TG of untreated GHD children were
      higher than those in treated subjects and healthy controls. Fasting TNF-alpha,
      CRP, and fibrinogen concentrations of untreated GHD adolescents were higher than
      those in healthy controls, but similar to those of GH-treated GHD adolescents.
      Although fibrinogen levels increased after a high-fat meal in GHD adolescents,
      CRP, TNF-alpha, and IL-6 concentrations did not increase further. Fasting and
      postprandial TG of untreated GHD adolescents were positively associated with
      fasting and postprandial CRP, and with postprandial TNF-alpha and IL-6
      concentrations. Fasting TG also correlated positively with fasting fibrinogen
      concentrations in untreated and treated GHD adolescents. CONCLUSIONS: The
      pronounced inflammatory response seen in GHD adolescents seems to be associated
      with the presence of elevated levels of fasting and postprandial TG, which may
      result in an increased susceptibility for premature atherosclerosis.

PMID- 15520770
TI  - Bone mineral acquisition in adolescents with type 1 diabetes.
AB  - OBJECTIVE: To track bone mineral acquisition in adolescents with type 1 diabetes
      (DM). STUDY DESIGN: Subjects were adolescents, ages 12 to 18 years, with DM
      (n=42) and a healthy regional reference (n=199). Measurements of tibia bone
      characteristics by peripheral quantitative computed tomography (pQCT) and spine
      and whole body (WB) by dual-energy x-ray absorptiometry (DEXA), anthropometrics,
      and lifestyle questionnaires were obtained during a 12-month period. Disease
      duration, insulin dose, renal function, and glycosylated hemoglobin (HbA1c)
      values for the previous 12 months were recorded. RESULTS: Body size and
      maturation were similar between groups. DM had lower tibia, spine, and WB bone
      characteristics but greater muscle mass (LBM) and lower bone mineral content
      (BMC)/LBM at baseline and 12 months. Annual gains for tibia cortical bone and WB
      BMC/LBM were lower and inversely related to HbA1c levels (R=-0.36 to -0.51),
      whereas spine area and density and WBLBM were greater and were predicted by
      pubertal-driven growth. Overall, the DM cohort had 8.5% less WB BMC/LBM,
      suggesting that bone mineral deposition was not adequately adapted to muscle
      gains. CONCLUSIONS: Adolescents with type 1 diabetes continue to have smaller
      bone mass and bone size despite normal growth and maturation. Poor metabolic
      control appears to negatively influence bone mineral acquisition.

PMID- 15520771
TI  - Testicular microlithiasis: an unreported feature of McCune-Albright syndrome in
      males.
AB  - OBJECTIVE: To ascertain the incidence of testicular microlithiasis (TM) in boys
      with McCune-Albright syndrome (MAS). STUDY DESIGN: Study population consisted of
      8 boys with MAS whose medical records were reviewed with emphasis on their past
      genitourinary histories. All of the boys underwent a clinical and
      ultrasonographic (US) scanning of the scrotal and inguinal regions. US results in
      boys with MAS were compared with those obtained in two control populations
      consisting of 20 healthy subjects and 12 boys with idiopathic and untreated
      central precocious puberty (CPP). RESULTS: Clinical examination revealed
      urological abnormalities in no patients, whereas US showed a typical picture of
      TM in 5 of 8 boys. TM was observed in none of the subjects belonging to control
      populations (v=15.2 and 11.3, respectively; P <.001). CONCLUSIONS: In a series of
      8 boys with MAS we demonstrated a high prevalence (62%) of TM that was associated
      with neither malignant nor nonmalignant conditions. This finding is unlikely to
      be only occasional, considering the very low prevalence of TM reported until now
      in healthy children and young adults and in our results in control populations.
      TM may be another marker for MAS.

PMID- 15520772
TI  - Idiopathic intracranial hypertension in cystinosis.
AB  - OBJECTIVES: To report a high frequency of idiopathic intracranial hypertension
      (IIH) in patients with cystinosis and to speculate on the relationship between
      these two disorders. STUDY DESIGN: Retrospective case series and review of the
      literature regarding risk factors for the development of IIH in cystinosis.
      RESULTS: Eight patients with cystinosis had documented papilledema, normal
      neuroimaging of the brain, cerebrospinal fluid (CSF) opening pressure greater
      than 200 mm of H2O, and normal CSF composition. No common medication, condition,
      or disease except cystinosis was found in these persons. Six of the patients had
      received prednisone, growth hormone, cyclosporine, oral contraceptives, vitamin
      D, or levothyroxine at the time of onset of IIH. Five patients had previous renal
      transplants. CONCLUSION: No single risk factor for the development of IIH linked
      IIH to cystinosis in our patients. However, thrombosis susceptibility as a result
      of renal disease or impaired CSF reabsorption in the arachnoid villi as a result
      of cystine deposition might lead to the development of IIH in cystinosis.

PMID- 15520780
TI  - Perinatal or early-postnatal cytomegalovirus infection in preterm infants under
      34 weeks gestation born to CMV-seropositive mothers within a high-seroprevalence
      population.
AB  - In a prospective study, we evaluated the frequency, correlates, and clinical
      significance of perinatal or early-postnatal cytomegalovirus (CMV) infection in
      <34-week-gestation infants (n=95) born to CMV-seropositive mothers. None had
      congenital CMV infection. Overall, 21 (22.1%; 95% CI=14.2-31.8) infants were
      found to be infected; 10 excreted CMV at <60 days, and 11 had later excretion.
      Blood transfusion, birth weight, and vaginal delivery were not associated
      factors. Receiving natural breast milk within the first 30 days (OR=4.5, P=.02)
      or for >30 days (OR=7.9, P <.01) was associated with infection. Only one (4.8%)
      of the infected infants was symptomatic. For <34-week-gestation infants,
      frequency of perinatal and early-postnatal CMV infection is high. Early or
      prolonged exposure to breast milk is an associated factor. However, most
      infections are asymptomatic, indicating that CMV infection in preterm infants
      within such a population is a serious problem infrequently.

PMID- 15520781
TI  - Variability of markers of inflammation and infection in induced sputum in
      children with cystic fibrosis.
AB  - To determine reproducibility of inflammatory marker concentrations in induced
      sputum from subjects with cystic fibrosis (CF), 15 nonexpectorating children, 6
      to 13 years of age with mild CF lung disease, underwent 3 weekly sputum
      inductions with 3% saline. Neutrophil elastase concentration and bacterial
      cultures were reproducible. This study provides useful information for
      investigators designing trials of anti-inflammatory therapies in CF involving
      sputum induction.

PMID- 15520782
TI  - Childhood primary angiitis of the central nervous system: two biopsy-proven
      cases.
AB  - Primary angiitis of the central nervous system is a rare idiopathic vasculitis
      predominantly affecting the central nervous system. The literature includes 10
      histologically confirmed cases in childhood. We identify two additional cases,
      one presenting with both uveitis and cerebrospinal fluid neutrophilic
      pleocytosis, which has not been reported previously, and demonstrate the
      importance of biopsy in suspected cases.

PMID- 15520784
TI  - Two siblings with lethal pneumococcal meningitis in a family with a mutation in
      Interleukin-1 receptor-associated kinase 4.
AB  - We describe two siblings with one confirmed and one inferred homozygous base pair
      deletion in the gene for interleukin-1-related kinase 4 (IRAK-4) who died of
      pneumococcal meningitis at 2 and 14 months, respectively. Interleukin-1-related
      kinase 4 deficiency is a potentially lethal immunodeficiency characterized by a
      poor inflammatory response to pyogenic infections.

PMID- 15520785
TI  - Short-term safety assessment in the use of intravenous zoledronic acid in
      children.
AB  - The clinical side effects of the potent new bisphosphonate zoledronic acid in
      children are unknown. In this study of 34 children with various bone disorders,
      the frequency of postinfusion flu-like illness, hypocalcemia, and
      hypophosphatemia was 85%, 74%, and 82%, respectively. No renal side effects were
      detected after up to 3 consecutive infusions.

PMID- 15520786
TI  - Neonatal type IV glycogen storage disease associated with "null" mutations in
      glycogen branching enzyme 1.
AB  - The fatal neonatal form of type IV glycogen storage disease (GSD IV) was
      diagnosed on light and electron microscopy and by analysis of GBE1 , the gene
      encoding glycogen branching enzyme. We report two novel truncating mutations, as
      well as the first genomic mutational analysis of GBE1 using denaturing high
      performance liquid chromatography.

PMID- 15520787
TI  - Purine nucleoside phosphorylase deficiency (PNP-def) presenting with lymphopenia
      and developmental delay: successful correction with umbilical cord blood
      transplantation.
AB  - Purine nucleoside phosphorylase deficiency is a primary immunodeficiency syndrome
      characterized by the triad of recurrent infection, neurologic dysfunction, and
      autoimmunity. This patient presented atypically with few infections and normal T
      cell function. Progressive lymphopenia, ataxia, and developmental delay led to
      diagnosis. Umbilical cord blood transplantation corrected the immunodeficiency.

PMID- 15520788
TI  - Doppler echocardiography and MR angiography for diagnosis of systolic murmurs in
      pulmonary sequestration.

PMID- 15520789
TI  - Gastric suction at birth: not an innocent bystander.

PMID- 15520790
TI  - Diagnostic value of food specific IgE antibodies in children with immediate
      digestive symptoms to cow's milk.

PMID- 15520791
TI  - Molecular genetics and genomics of heart failure.
AB  - Heart failure is a major disease burden worldwide, and its incidence continues to
      increase as premature deaths from other cardiovascular conditions decline.
      Although the overall molecular portrait of this multifactorial disease remains
      incomplete, molecular and genetic studies have implicated, in recent decades,
      various pathways and genes that participate in the pathophysiology of heart
      failure. Here, we highlight the current understanding of the molecular and
      genetic basis of heart failure and show how recently developed genomic tools are
      providing a new perspective on this complex disease.

PMID- 15520792
TI  - Biological robustness.
AB  - Robustness is a ubiquitously observed property of biological systems. It is
      considered to be a fundamental feature of complex evolvable systems. It is
      attained by several underlying principles that are universal to both biological
      organisms and sophisticated engineering systems. Robustness facilitates
      evolvability and robust traits are often selected by evolution. Such a mutually
      beneficial process is made possible by specific architectural features observed
      in robust systems. But there are trade-offs between robustness, fragility,
      performance and resource demands, which explain system behaviour, including the
      patterns of failure. Insights into inherent properties of robust systems will
      provide us with a better understanding of complex diseases and a guiding
      principle for therapy design.

PMID- 15520793
TI  - Quantitative genetic analyses of complex behaviours in Drosophila.
AB  - Behaviours are exceptionally complex quantitative traits. Sensitivity to
      environmental variation and genetic background, the presence of sexual
      dimorphism, and the widespread functional pleiotropy that is inherent in
      behavioural phenotypes pose daunting challenges for unravelling their underlying
      genetics. Drosophila melanogaster provides an attractive system for elucidating
      the unifying principles of the genetic architectures that drive behaviours, as
      genetically identical individuals can be reared rapidly in controlled
      environments and extensive publicly accessible genetic resources are available.
      Recent advances in quantitative genetic and functional genomic approaches now
      enable the extensive characterization of complex genetic networks that mediate
      behaviours in this important model organism.

PMID- 15520794
TI  - Human brain evolution: insights from microarrays.
AB  - Several recent microarray studies have compared gene-expression patterns n
      humans, chimpanzees and other non-human primates to identify evolutionary changes
      that contribute to the distinctive cognitive and behavioural characteristics of
      humans. These studies support the surprising conclusion that the evolution of the
      human brain involved an upregulation of gene expression relative to non-human
      primates, a finding that could be relevant to understanding human cerebral
      physiology and function. These results show how genetic and genomic methods can
      shed light on the basis of human neural and cognitive specializations, and have
      important implications for neuroscience, anthropology and medicine.

PMID- 15520795
TI  - Sharing genomes: an integrated approach to funding, managing and distributing
      genomic clone resources.
AB  - National biological resource centres have a vital role in archiving and
      distributing biological reagents that result from large-scale genome programmes.
      These reagents are invaluable to the research community as they enable
      independent validation of results disclosed in peer review and provide tools that
      facilitate the next steps in discovery science. Here we address the crucial
      issues of open access, quality of materials, integration with public databases
      and sustainability of resources.

PMID- 15520796
TI  - The social and ethical issues of post-genomic human biobanks.
AB  - Biobanking - the organized collection of biological samples and associated data -
      ranges in scope from small collections of samples in academic or hospital
      settings to large-scale national repositories. Biobanks raise many ethical
      concerns, to which authorities are responding by introducing specific
      regulations. Genomics research, which thrives on the sharing of samples and
      information, is affected by two prominent ethical questions: do ethical
      principles prevent or promote the sharing of stored biological resources? How
      does the advent of large-scale biobanking alter the way in which ethical issues
      are addressed?

PMID- 15520797
TI  - The nature of stem cells: state rather than entity.
AB  - Stem cells are endowed with self-renewal and multipotential differentiation
      capacities. Contrary to the expectation that stem cells would selectively express
      specific genes, these cells have a highly promiscuous gene-expression pattern.
      Here, I suggest that the transient stem cell state, termed the 'stem state', may
      be assumed by any cell and that the search for specific genes expressed by all
      stem cells, which would characterize the stem cell as a cell type, might be
      futile.

PMID- 15520798
TI  - Lost in translation.

PMID- 15520799
TI  - Reductionism and complexity in molecular biology. Scientists now have the tools
      to unravel biological and overcome the limitations of reductionism.

PMID- 15520800
TI  - GM crops: good or bad? Those who choose the questions determine the answers.

PMID- 15520801
TI  - Building organs piece by piece. Accomplishments and future perspectives in tissue
      engineering.

PMID- 15520802
TI  - Fashion of the times. The emergence and evolution of new research fields is as
      much determined by scientific interest as it is by social, political and economic
      pressures.

PMID- 15520803
TI  - GM plants for your health. The acceptance of GM crops in Europe might grow as
      soon as the first products to offer direct benefits for consumer health become
      available.

PMID- 15520805
TI  - Natively unfolded domains in endocytosis: hooks, lines and linkers.
AB  - It is commonly assumed that a protein must adopt a tertiary structure to achieve
      its active native state and that regions of a protein that are devoid of alpha
      helix or beta-sheet structures are functionally inert. Although extended proline
      rich regions are recognized as presenting binding motifs to, for example, Src
      homology 2 (SH2) and SH3 domains, the idea persists that natively unfolded
      regions in functional proteins are simply 'spacers' between the folded domains.
      Such a view has been challenged in recent years and the importance of natively
      unfolded proteins in biology is now being recognized. In this review, we
      highlight the role of natively unfolded domains in the field of endocytosis, and
      show that some important endocytic proteins lack a traditionally folded structure
      and harbour important binding motifs in their unstructured linker regions.

PMID- 15520806
TI  - On the mechanism of protein palmitoylation.
AB  - Protein palmitoylation or, more specifically, S-acylation is a reversible post
      translational lipid modification. Despite the identification of several proteins
      that are altered in this way, our understanding of the enzymology of this process
      has been hampered by the lack of well-characterized acyltransferases. We now know
      of three proteins in Saccharomyces cerevisiae that promote palmitoylation:
      effector of Ras function (Erf2), ankyrin-repeat-containing protein (Akr1) and the
      SNARE protein Ykt6. Erf2 and Akr1 are integral membrane proteins that contain a
      cysteine-rich domain and an Asp-His-His-Cys motif, both of which catalyse
      acylation at the carboxyl terminus of their target proteins. Recently, we
      discovered that Ykt6 mediates the amino-terminal acylation of the fusion protein
      Vac8. Even though these three proteins differ in sequence, topology, size and
      substrate specificity, they might function in a similar manner. In this review,
      we discuss these observations in the context of a potential general mechanism of
      acylation.

PMID- 15520807
TI  - The RAF proteins take centre stage.
AB  - Since their discovery over 20 years ago, the RAF proteins have been intensely
      studied. For most of that time, the focus of the field has been the C-RAF isoform
      and its role as an effector of the RAS proteins. However, a report that
      implicates B-RAF in human cancer has highlighted the importance of all members of
      this protein kinase family and recent studies have uncovered intriguing new data
      relating to their complex regulation and biological functions.

PMID- 15520808
TI  - Targeting Rab GTPases to distinct membrane compartments.
AB  - Rab GTPases are key to membrane-trafficking events in eukaryotic cells, and human
      cells contain more than 60 Rab proteins that are localized to distinct
      compartments. The recent determination of the structure of a monoprenylated Rab
      GTPase bound to GDP-dissociation inhibitor provides new molecular details that
      are relevant to models of Rab delivery. The further discovery of an integral
      membrane protein that can dissociate prenylated Rab proteins from GDP
      dissociation inhibitor gives new insights into the mechanisms of Rab
      localization.

PMID- 15520809
TI  - Molecular mechanisms of caspase regulation during apoptosis.
AB  - Caspases, which are the executioners of apoptosis, comprise two distinct classes,
      the initiators and the effectors. Although general structural features are shared
      between the initiator and the effector caspases, their activation, inhibition and
      release of inhibition are differentially regulated. Biochemical and structural
      studies have led to important advances in understanding the underlying molecular
      mechanisms of caspase regulation. This article reviews these latest advances and
      describes our present understanding of caspase regulation during apoptosis.

PMID- 15520810
TI  - Strategies for RNA folding and assembly.
AB  - RNA is structurally very flexible, which provides the basis for its functional
      diversity. An RNA molecule can often adopt different conformations, which enables
      the regulation of its function through folding. Proteins help RNAs reach their
      functionally active conformation by increasing their structural stability or by
      chaperoning the folding process. Large, dynamic RNA-protein complexes, such as
      the ribosome or the spliceosome, require numerous proteins that coordinate
      conformational switches of the RNA components during assembly and during their
      respective activities.

PMID- 15520811
TI  - The LIM domain: from the cytoskeleton to the nucleus.
AB  - First described 15 years ago as a cysteine-rich sequence that was common to a
      small group of homeodomain transcription factors, the LIM domain is now
      recognized as a tandem zinc-finger structure that functions as a modular protein
      binding interface. LIM domains are present in many proteins that have diverse
      cellular roles as regulators of gene expression, cytoarchitecture, cell adhesion,
      cell motility and signal transduction. An emerging theme is that LIM proteins
      might function as biosensors that mediate communication between the cytosolic and
      the nuclear compartments.

PMID- 15520812
TI  - Tackling the challenges of interdisciplinary bioscience.
AB  - The ultimate goal for biology is to become a science that formulates our
      understanding of subcellular, cellular and multicellular systems in terms of
      quantitative, holistic models that are underpinned by the rigorous principles of
      the physical sciences and mathematics. This can only be achieved through
      interdisciplinary research that draws heavily on the expertise and technologies
      of the physical sciences, engineering, computation and mathematics. Here, I
      discuss the benefits and challenges (both intellectual and practical) of
      interdisciplinary bioscience.

PMID- 15520814
TI  - Molecular, cellular and functional imaging of atherothrombosis.
AB  - Recent years have seen a dramatic expansion in our knowledge of the events of
      atherogenesis and in the availability of drugs that can retard the progression -
      and even induce the regression - of this disease process. Our understanding has
      been advanced considerably by developments in genetics and molecular biology and
      by the use of genetically modified mouse models that have provided key
      mechanistic insights. Increasingly sophisticated imaging techniques will
      capitalize on these advances by bringing forward diagnosis, enhancing disease
      characterization and providing more precise evaluation of the effects of
      treatment. In this review, techniques for imaging atherosclerosis and thrombosis
      will be discussed. Particular attention will be given to magnetic resonance
      imaging techniques that enable lesion characterization and allow the targeted
      imaging of cells, molecules and biological processes. Emphasis is given to the
      potential contribution of magnetic resonance imaging methods to therapeutic
      monitoring, drug delivery and drug discovery.

PMID- 15520813
TI  - Happy Hollidays: 40th anniversary of the Holliday junction.
AB  - In 1964, the geneticist Robin Holliday proposed a mechanism of DNA-strand
      exchange that attempted to explain gene-conversion events that occur during
      meiosis in fungi. His proposal marked the birthday of the now famous cross
      stranded DNA structure, or Holliday junction. To understand the importance of the
      Holliday model we must look back in the history of science beyond the last 40
      years, to a time when theories of heredity were being proposed by Gregor Johann
      Mendel.

PMID- 15520815
TI  - Drugs as materials: valuing physical form in drug discovery.
AB  - Traditionally, potency and selectivity (and to some extent metabolism) have been
      the key parameters to consider in the process of discovering new drug candidates.
      Recently, heads of research and CEOs have been learning a new reality: drugs can
      move around the body and act at the molecular level, but the chemical and
      material properties of their physical form need to be identified and optimized
      for in vivo performance, reliable manufacture and the protection of intellectual
      property. This review discusses the challenge of pharmaceutical materials
      discovery, and suggests strategies for addressing the characterization and
      evaluation of physico-chemical and material properties in the drug discovery and
      development process.

PMID- 15520816
TI  - Docking and scoring in virtual screening for drug discovery: methods and
      applications.
AB  - Computational approaches that 'dock' small molecules into the structures of
      macromolecular targets and 'score' their potential complementarity to binding
      sites are widely used in hit identification and lead optimization. Indeed, there
      are now a number of drugs whose development was heavily influenced by or based on
      structure-based design and screening strategies, such as HIV protease inhibitors.
      Nevertheless, there remain significant challenges in the application of these
      approaches, in particular in relation to current scoring schemes. Here, we review
      key concepts and specific features of small-molecule-protein docking methods,
      highlight selected applications and discuss recent advances that aim to address
      the acknowledged limitations of established approaches.

PMID- 15520817
TI  - Principles for modulation of the nuclear receptor superfamily.
AB  - Nuclear receptors are major targets for drug discovery and have key roles in
      development and homeostasis, as well as in many diseases such as obesity,
      diabetes and cancer. This review provides a general overview of the mechanism of
      action of nuclear receptors and explores the various factors that are
      instrumental in modulating their pharmacology. In most cases, the response of a
      given receptor to a particular ligand in a specific tissue will be dictated by
      the set of proteins with which the receptor is able to interact. One of the most
      promising aspects of nuclear receptor pharmacology is that it is now possible to
      develop ligands with a large spectrum of full, partial or inverse agonist or
      antagonist activities, but also compounds, called selective nuclear receptor
      modulators, that activate only a subset of the functions induced by the cognate
      ligand or that act in a cell-type-selective manner.

PMID- 15520818
TI  - Functional genomics to new drug targets.
AB  - The completion of the sequencing of the human genome, and those of other
      organisms, is expected to lead to many potential new drug targets in various
      diseases, and it is predicted that novel therapeutic agents will be developed
      against such targets. The role of functional genomics in modern drug discovery is
      to prioritize these targets and to translate that knowledge into rational and
      reliable drug discovery. Here, we describe the field of functional genomics and
      review approaches that have been applied to drug discovery, including RNA
      profiling, proteomics, antisense and RNA interference, model organisms and high
      throughput, genome-wide overexpression or knockdowns, and outline the future
      directions that are likely to yield new drug targets from genomics.

PMID- 15520819
TI  - Stopping clinical trials by design.
AB  - Before any clinical trial begins, a detailed trial protocol must be prepared. The
      authority of the trial results will depend on the quality of this document. In
      many protocols, a key component is a plan for a series of interim analyses of the
      accumulating trial data, and a 'stopping rule' based on them. Such a rule might
      be intended to prevent participants from continuing to receive a drug that
      already seems to be unsafe, or to allow a successful drug to become generally
      available as soon as sufficient evidence of its advantages has been collected.
      There has been considerable misunderstanding of these rules, and controversies
      associated with them. Here, I discuss why this might be, and what can be done to
      promote their successful and beneficial use in the future.

PMID- 15520820
TI  - An evaluation of factors predicting long-term response to thalidomide in 234
      patients with relapsed or resistant multiple myeloma.
AB  - The aim of this study was to assess the prognostic value of pretreatment clinical
      and laboratory parameters in refractory or relapsed multiple myeloma (MM)
      patients who have a long-term response to thalidomide (THAL), lasting at least 18
      months. The study was carried out on 234 patients who received THAL for
      relapsed/refractory myeloma. Out of the 234 patients, 129 patients (55.1%)
      responded to THAL with a mean response duration of 11.9 months (ranging from 1 to
      48) and an overall survival rate of 20.3 months (ranging 1-55 months). In 64
      patients (27.4% of the whole group), the response to THAL lasted > or =18 months
      with a mean response lasting 24 months. Statistical analysis of the group of
      nonresponders and patients with long-term response to THAL showed a significantly
      higher serum albumin level (P=0.0003) and haemoglobin level (P=0.05), as well as
      a lower beta2 microglobulin (beta2M) (P=0.022), LDH (P=0.045) serum level in
      patients with long-term response. In this study, the LDH and serum albumin level
      were predictors for response to THAL therapy. The beta2M serum level was not a
      predictor for response to THAL. The albumin serum level was the best parameter
      distinguishing the group of patients with long-term response to THAL from the
      entire responding group (P=0.02).

PMID- 15520821
TI  - Childhood and maternal infections and risk of acute leukaemia in children with
      Down syndrome: a report from the Children's Oncology Group.
AB  - Children with Down syndrome (DS) are highly susceptible to acute leukaemia. Given
      the potential role of infections in the aetiology of leukaemia in children
      without DS, we investigated whether there was an association between early-life
      infections and acute leukaemia in children with DS. Maternal infections during
      pregnancy were also examined. We enrolled 158 incident cases of acute leukaemia
      in children with DS (97 acute lymphoblastic leukaemia (ALL) and 61 acute myeloid
      leukaemia (AML)) diagnosed at Children's Oncology Group institutions between 1997
      and 2002. DS controls (N=173) were selected from the cases' primary care clinics
      and frequency matched on age at leukaemia diagnosis. Data were collected on
      demographics, child's medical history, mother's medical history, and other
      factors by maternal interview. Analyses were conducted using unconditional
      logistic regression adjusted for potential confounders. A significant negative
      association was observed between acute leukaemia and any infection in the first 2
      years of life (adjusted odds ratio (OR)=0.55, 95% confidence interval (CI) (0.33
      0.92); OR=0.53, 95% CI (0.29-0.97); and OR=0.59, 95% CI (0.28-1.25) for acute
      leukaemia combined, ALL, and AML respectively). The association between acute
      leukaemia and maternal infections during pregnancy was in the same direction but
      not significant. This study offers support for the hypothesis that early-life
      infections may play a protective role in the aetiology of acute leukaemia in
      children with DS.

PMID- 15520822
TI  - Evaluation of hypoxia in an experimental rat tumour model by
      [(18)F]fluoromisonidazole PET and immunohistochemistry.
AB  - This study aimed to evaluate tumour hypoxia by comparing
      [(18)F]Fluoromisonidazole uptake measured using positron emission tomography
      ([(18)F]FMISO-PET) with immunohistochemical (IHC) staining techniques. Syngeneic
      rhabdomyosarcoma (R1) tumour pieces were transplanted subcutaneously in the
      flanks of WAG/Rij rats. Tumours were analysed at volumes between 0.9 and 7.3
      cm(3). Hypoxic volumes were defined using a 3D region of interest on 2 h
      postinjection [(18)F]FMISO-PET images, applying different thresholds (1.2-3.0).
      Monoclonal antibodies to pimonidazole (PIMO) and carbonic anhydrase IX (CA IX),
      exogenous and endogenous markers of hypoxia, respectively, were used for IHC
      staining. Marker-positive fractions were microscopically measured for each
      tumour, and hypoxic volumes were calculated. A heterogeneous distribution of
      hypoxia was observed both with histology and [(18)F]FMISO autoradiography. A
      statistically significant correlation (P<0.05) was obtained between the hypoxic
      volumes defined with [(18)F]FMISO-PET and the volumes derived from the PIMO
      stained tumour sections (r=0.9066; P=0.0001), regardless of the selected
      threshold between 1.4 and 2.2. A similar observation was made with the CA IX
      staining (r=0.8636; P=0.0006). The relationship found between [(18)F]FMISO-PET
      and PIMO- and additionally CA IX-derived hypoxic volumes in rat rhabdomyosarcomas
      indicates the value of the noninvasive imaging method to measure hypoxia in whole
      tumours.

PMID- 15520823
TI  - Modulation of human Valpha24(+)Vbeta11(+) NKT cells by age, malignancy and
      conventional anticancer therapies.
AB  - Immunotherapy strategies aimed at increasing human Valpha24(+)Vbeta11(+) natural
      killer T (NKT) cell numbers are currently a major focus. To provide further
      information towards the goal of NKT cell-based immunotherapy, we assessed the
      effects of age, cancer status and prior anticancer treatment on NKT cell numbers
      and their expansion capacity following alpha-galactosylceramide (alpha-GalCer)
      stimulation. The percentage and absolute number of peripheral blood NKT cells was
      assessed in 40 healthy donors and 109 solid cancer patients (colorectal (n=33),
      breast (n=10), melanoma (n=17), lung (n=8), renal cell carcinoma (n=10), other
      cancers (n=31)). Responsiveness to alpha-GalCer stimulation was also assessed in
      28 of the cancer patients and 37 of the healthy donors. Natural killer T cell
      numbers were significantly reduced in melanoma and breast cancer patients. While
      NKT numbers decreased with age in healthy donors, NKT cells were decreased in
      these cancer subgroups despite age and sex adjustments. Prior radiation treatment
      was shown to contribute to the observed reduction in melanoma patients. Although
      cancer patient NKT cells were significantly less responsive to alpha-GalCer
      stimulation, they remained capable of substantial expansion. Natural killer T
      cells are therefore modulated by age, malignancy and prior anticancer treatment;
      however, cancer patient NKT cells remain capable of responding to alpha-GalCer
      based immenotherapies.

PMID- 15520824
TI  - Contemporary update of cancer control after radical prostatectomy in the UK.
AB  - Despite a significant increase of the number of radical prostatectomies (RPs) to
      treat organ-confined prostate cancer, there is very limited documentation of its
      oncological outcome in the UK. Pathological stage distribution and changes of
      outcome have not been audited on a consistent basis. We present the results of a
      multicentre review of postoperative predictive variables and prostatic-specific
      antigen (PSA) recurrence after RP for clinically organ-confined disease. In all,
      854 patient's notes were audited for staging parameters and follow-up data
      obtained. Patients with neoadjuvant and adjuvant treatment as well as patients
      with incomplete data and follow-up were excluded. Median follow-up was 52 months
      for the remaining 705 patients. The median PSA was 10 ng ml(-1). A large
      migration towards lower PSA and stage was seen. This translated into improved PSA
      survival rates. Overall Kaplan-Meier PSA recurrence-free survival probability at
      1, 3, 5 and 8 years was 0.83, 0.69, 0.60 and 0.48, respectively. The 5-year PSA
      recurrence-free survival probability for PSA ranges <4, 4.1-10, 10.1-20 and >20
      ng ml(-1) was 0.82, 0.73, 0.59 and 0.20, respectively (log rank, P<0.0001). PSA
      recurrence-free survival probabilities for pathological Gleason grade 2-4, 5 and
      6, 7 and 8-10 at 5 years were 0.84, 0.66, 0.55 and 0.21, respectively (log rank,
      P<0.0001). Similarly, 5-year PSA recurrence-free survival probabilities for
      pathological stages T2a, T2b, T3a, T3b and T4 were 0.82, 0.78, 0.48, 0.23 and
      0.12, respectively (log rank, P=0.0012). Oncological outcome after RP has
      improved over time in the UK. PSA recurrence-free survival estimates are less
      optimistic compared to quoted survival figures in the literature. Survival
      figures based on pathological stage and Gleason grade may serve to counsel
      patients postoperatively and to stratify patients better for adjuvant treatment.

PMID- 15520825
TI  - Interactions between physical activity and variants of the genes encoding
      uncoupling proteins -2 and -3 in relation to body weight changes during a 10-y
      follow-up.
AB  - OBJECTIVE: To examine interactions between physical activity and possibly
      functional variants of the genes encoding uncoupling proteins -2 and -3 in
      relation to body weight change. We hypothesize that physical inactivity acts
      synergistically with a 45 bp insertion variant in the 3'untranslated region
      (3'UTR) of the UCP2-gene and with a t-allele of codon -55 in the promoter of the
      UCP3-gene in relation to subsequent weight change. DESIGN: Population-based
      longitudinal study of cohorts of juvenile obese and nonobese men, who were
      identified at the mandatory draft board examination in Copenhagen and adjacent
      regions at a median age of 19 y in 1943-77 and later examined at general health
      surveys in 1981-83 and 1991-93. The juvenile obese cohort included 568 men who at
      the draft board had a BMI > or =31 kg/m2 and the cohort of controls included 717
      randomly selected draftees. MEASUREMENTS: Height and weight were measured, and
      information about physical activity was collected from a self-administered
      questionnaire. The genotyping of the polymorphisms was performed using RFLP
      techniques. The main outcome measure was change in BMI during the 10-y follow-up
      period. Additional outcome measures were obesity, waist circumference and body
      fat mass index measured at follow-up. RESULTS: Physical activity, the 3'UTR
      insertion polymorphism and the -55 c/t polymorphism were not consistently
      associated with changes in BMI, and there were no evidence for interactions
      between the UCP-variants and physical activity in relation to changes in BMI. No
      evidence for interaction between the UCP-variants and physical activity was found
      in relation to the additional obesity measures. CONCLUSION: This study does not
      support that interactions between physical activity and variants in the UCP2- or
      UCP3-gene are major determinants of subsequent weight changes in Danish Caucasian
      men.

PMID- 15520827
TI  - Composition of the fat-free mass in obese and nonobese children: matched case
      control analyses.
AB  - OBJECTIVE: Most body composition techniques assume constant properties of the fat
      free mass (FFM), such as hydration, density and mineralisation. Previous studies
      suggested that FFM composition may change in childhood obesity; however, this
      issue has not been investigated in detail. AIM: To compare FFM composition in
      obese and nonobese children. DESIGN: Observational matched case-control analyses.
      SUBJECTS: A total of 28 obese children (13 boys, 15 girls) and 22 nonobese
      children (10 boys, 12 girls) aged 7-14 y. Obesity was defined as body mass index
      centile >95. METHODS: Measurements were made of weight, height, total body water,
      and body volume. Bone mineral content was estimated in a subsample. Body
      composition was calculated using three- and four-component models. RESULTS:
      According to the three-component model (n=22 matched pairs), obese children had
      greater hydration (P<0.05), and reduced density (P=0.057) of FFM. According to
      the four component model (n=11 pairs), obese children had greater hydration
      (P<0.01) and reduced density (P<0.002) of FFM. The mineralisation of FFM was
      increased, but not significantly so. CONCLUSION: The greater hydration and
      reduced density of FFM of obese children should be taken into account if body
      composition is to be measured with optimum accuracy during treatment programmes.
      These differences may be addressed by using multicomponent rather than two
      component models of body composition. Although the greater mineralisation of FFM
      in obese children was not significant in the present study, the four-component
      model is best able to address the combined differences in hydration and
      mineralisation that occur in childhood obesity.

PMID- 15520826
TI  - Monocyte chemoattractant protein-1 is produced in isolated adipocytes, associated
      with adiposity and reduced after weight loss in morbid obese subjects.
AB  - BACKGROUND: Obesity is associated with insulin resistance and premature
      atherosclerosis. The human adipose tissue produce several adipokines including
      monocyte chemoattractant protein (MCP)-1, associated with cardiovascular disease
      and found to be involved in the pathogenesis of atherosclerosis in vitro.
      OBJECTIVE: (1) To compare mRNA levels of MCP-1, leptin and a macrophage-specific
      marker (CD68) in isolated adipocytes vs stromal-vascular (SV) cells, (2) to
      compare mRNA levels of MCP-1 in human adipose tissue to circulating MCP-1 and
      adiposity (eg BMI: kg/m2) and (3) investigate the effect of weight loss in obese
      subjects on circulating MCP-1 and leptin. RESULTS: (1) MCP-1 and CD68 mRNA levels
      in isolated adipocytes vs SV cells were 17% (P<0.01) and approximately 2%
      (P<0.001), respectively. Leptin mRNA levels in SV cells were approximately 1% of
      that in isolated adipocytes (P<0.01). (2) MCP-1 mRNA levels correlated with
      circulating MCP-1 (P<0.05) and BMI (P<0.05). (3) A 12% weight loss (P<0.001) was
      associated with a 25% decrease in insulin levels (P<0.01). Circulating MCP-1 and
      leptin decreased by 20% (P<0.001) and by 24% (P<0.001), respectively. DISCUSSION:
      The findings demonstrate that MCP-1 is produced in isolated human adipocytes. In
      addition, the findings suggest that MCP-1 may be involved in obesity-related
      health complications and support the hypothesis that weight loss is beneficial by
      improving the low-grade inflammation observed in obesity.

PMID- 15520828
TI  - Use of surgery to aid weight reduction-experience of two regions of Northern
      England: a database study.
AB  - OBJECTIVE: To determine the usage of surgery in the management of obesity.
      DESIGN: Analysis of routine statistics. DATA SOURCES: Hospital Episode Statistics
      extract held by Public Health Observatories. GEOGRAPHICAL AREAS: Two Government
      Office Regions in England with a population of 7.6 million. TIME PERIOD: Data
      analysed in the study covered the 6 y 1996/1997-2001/2002. RESULTS: The
      availability and uptake of surgery for obesity in the two regions was hugely
      variable. The overall utilisation of the procedures examined (OPCS operation
      codes: G30.1, G30.2, G32.10, G61.00) was 5.6 per million per annum, but ranged by
      Primary Care Trust from zero (the case in eight of the 50 PCTs in the two
      regions) to 24.0 operations per million per year. The rates of access to this
      surgery differed over six-fold between the two regions (1.4 operations per year
      per million population to 7.9 operations per year per million population). The
      PCTs with the highest rates of surgery, were those closest to the large providers
      of service. CONCLUSIONS: Access to this intervention is highly variable. Primary
      Care Trusts in England and service providers need to ensure that there is
      appropriate access to this effective procedure in carefully selected cases. The
      surgical expertise required for these operations could be concentrated in fewer
      centres.

PMID- 15520829
TI  - Recognition, diagnosis and management of obesity after myocardial infarction.
AB  - OBJECTIVE: We investigated the documentation of obesity as a medical problem, and
      subsequent management recommendations, in patients after myocardial infarction
      (MI). DESIGN: We performed a cross-sectional analysis of a randomly selected
      sample of 627 patients discharged after an MI, from five US teaching hospitals
      between 1/1/01 and 12/31/02. Information was extracted from clinical notes using
      standardized definitions. RESULTS: Mean body mass index (BMI) was 31+/-13 kg/m2,
      which was documented in only 14% of patients and had to be calculated post hoc in
      the rest. Waist circumference and waist/hip ratio were not documented at all; 83%
      of patients were overweight, 55% obese, and 8% morbidly obese. In only 20% of
      patients with BMI> or =30 kg/m2 was the diagnosis of obesity documented either as
      a current medical problem, as part of past medical history or as a final
      diagnosis. A dietary counseling was carried out in 61% of patients with BMI> or
      =25 kg/m2 and in 61% of patients with BMI<25 kg/m2, P=0.96. Weight loss was
      described as part of the goals/plan at discharge in 7% of overweight and 9% of
      obese patients. There was no change in either the level of recognition of obesity
      (22 vs 19%, P=0.3) or in the proportion of obese patients for whom weight loss
      was described as part of the goals/plan at discharge (8 vs 10%, P=0.7) before
      (n=301) compared to after (n=326) the Call to Action in Obesity by the Surgeon
      General in December 2001. CONCLUSION: Obesity is underecognized, underdiagnosed
      and undertreated in persons with acute MI.

PMID- 15520830
TI  - The relation between obesity, abdominal fat deposit and the angiotensin
      converting enzyme gene I/D polymorphism and its association with coronary heart
      disease.
AB  - OBJECTIVE: To analyse the relation between overweight, obesity and fat
      distribution with I/D polymorphism of the angiotensin-converting enzyme (ACE)
      gene and its association with coronary heart disease (CHD). DESIGN: Cross
      sectional, case-control study. SUBJECTS: A total of 185 cases (141 males) who had
      suffered at least one episode of CHD and 182 controls (127 males). MEASUREMENTS:
      Body mass index, waist circumference, blood pressure, plasma total cholesterol,
      triglycerides, HDL cholesterol and fasting glucose were measured with standard
      methods, genotyping the I/D polymorphism of ACE gene. RESULTS: Obesity and
      abdominal fat deposit are associated with CHD in women, but not independently. We
      have found an association between obesity and abdominal fat deposit with the ACE
      gene I/D polymorphism in subjects with CHD. Subjects with CHD and DD or ID
      genotypes have significantly higher prevalence of obesity and abdominal fat
      deposit and higher values of weight and waist circumference. In addition, the DD
      and ID genotypes increased crude OR of obesity. The DD and ID genotypes of the
      ACE gene I/D polymorphism and BMI are independently associated with CHD.
      CONCLUSION: There is a relation between the type and grade of obesity with the
      genotypes of the ACE gene I/D polymorphism in subjects with CHD.

PMID- 15520832
TI  - Association and linkage of alpha-2A adrenergic receptor gene polymorphisms with
      childhood ADHD.
AB  - Attention-deficit hyperactivity disorder (ADHD) is a heritable disorder,
      prevalent from childhood through adulthood. Although the noradrenergic (NA)
      system is thought to mediate a portion of the pathophysiology of ADHD, genes in
      this pathway have not been investigated as frequently as those in the
      dopaminergic system. Previous association studies of one candidate gene in the NA
      system, ADRA2A, showed inconsistent results with regard to an MspI polymorphism.
      In the current study, two nearby single-nucleotide polymorphisms, which define
      HhaI and DraI restriction fragment length polymorphisms, were also genotyped and
      were in significant linkage disequilibrium with the MspI RFLP. Transmission
      disequilibrium tests (TDTs) in a sample of 177 nuclear families showed
      significant association and linkage of the DraI polymorphism with the ADHD
      combined subtype (P=0.03), and the quantitative TDT showed association of this
      polymorphism with the inattentive (P=0.003) and hyperactive-impulsive (P=0.015)
      symptom dimensions. The haplotype that contained the less common allele of the
      DraI polymorphism likewise showed a strong relationship with the inattentive
      (P=0.001) and hyperactive-impulsive (P=0.004) symptom dimensions. This study
      supports the hypothesis that an allele of the ADRA2A gene is associated and
      linked with the ADHD combined subtype and suggests that the DraI polymorphism of
      ADRA2A is linked to a causative polymorphism.

PMID- 15520834
TI  - Disability profile of patients with HTLV-I-associated myelopathy/tropical spastic
      paraparesis using the Functional Independence Measure (FIM).
AB  - STUDY DESIGN: Survey. OBJECTIVE: To determine the disability profile of a group
      of patients with human T-cell lymphotropic virus type I-associated
      myelopathy/tropical spastic paraparesis (HAM/TSP), using the Functional
      Independence Measure (FIM) to identify the most affected functional areas.
      SETTING: Reference center for HTLV Rio de Janeiro, Brazil. METHODS: A total of 72
      patients (49 female and 23 male), consecutively referred by tertiary care
      centers, were assessed using the FIM. RESULTS: The average FIM score was 108 (+/
      12 SD) ranging from 58 to 122. The lowest items scores were obtained in
      locomotion and bladder management. When divided into two groups (above, and below
      or equal to the average score), there were significant differences (P<0.05) in
      age at time of assessment, in the degree of muscular power and in low back pain.
      There were no significant differences in terms of age of onset and duration of
      the disease. CONCLUSIONS: The most affected areas in FIM motor items were
      locomotion (walk and stairs) and bladder management. Age, strength in lower limbs
      and low back pain interfere with functional activities in patients with HAM/TSP.
      The duration of the disease is not a significant factor for patient disabilities.
      The goals of rehabilitation in HAM/TSP patients should target the modifiable
      factors, such as pain, strength and the neurogenic bladder.

PMID- 15520831
TI  - Associations between prepulse inhibition and executive visual attention in
      children with the 22q11 deletion syndrome.
AB  - The 22q11 deletion syndrome (DS) results in the loss of approximately 30 gene
      copies and is associated with possible physical anomalies, varied learning
      disabilities, and a specific cluster of neurocognitive deficits, including
      primary impairment in working memory, executive visual attention, and
      sensorimotor processing. Retrospective studies have suggested that children with
      22q11DS are at 25 times greater risk of developing schizophrenia, thus
      specification of early brain network vulnerabilities among children with 22q11DS
      is critical. Previously, we reported that children with 22q11DS as compared with
      sibling controls had selective deficits in visual executive attention, and
      subsequently found lowered prepulse inhibition (PPI) in these same children.
      Visual executive attention and PPI recruit the same brain pathways linking
      prefrontal cortex to basal ganglia structures. To test the specificity of brain
      pathway vulnerability among children with 22q11DS, we examined visual executive
      attention and PPI paradigm data collected during the same test session from 21
      children with 22q11DS and 25 sibling controls. We predicted lower %PPI and less
      efficient executive attention scores, and a significant inverse correlation
      between measures. %PPI in children with 22q11DS as compared with sibling controls
      was 20% lower, and visual executive attention efficiency scores 40% worse. As
      predicted, %PPI was inversely correlated only with executive attention efficiency
      scores. The implications of these findings with regard to brain pathway
      vulnerability in children with 22q11DS are considered. These results suggest that
      children with 22q11DS have early functional abnormality in pathways linking the
      prefrontal cortex and basal ganglia.

PMID- 15520835
TI  - Foramen magnum decompression for the treatment of Arnold Chiari malformation type
      I with associated syringomyelia in an elderly patient.
AB  - STUDY DESIGN: Report of a rare case of an elderly patient with late onset of
      Arnold Chiari malformation type I with associated syringomyelia that was
      successfully treated with foramen magnum decompression. OBJECTIVE: To report this
      rare case along with a literature review. SETTING: Gifu, Japan. METHODS: A 69
      year-old woman with a 4-year history of dull pain in her right arm was referred
      to the clinic. After physical and radiographical examinations, she was diagnosed
      with Arnold Chiari malformation type I with associated syringomyelia. A foramen
      magnum decompression by the removal of the outer layer of the dura mater was
      performed. RESULTS: At 2 years postoperatively, MRI revealed a decrease in the
      size of the syringomyelia. Her symptoms had also remarkably improved.
      CONCLUSIONS: A rare case of symptomatic Arnold Chiari malformation type I with
      associated syringomyelia in an elderly woman was successfully treated with
      foramen magnum decompression by the removal of the outer layer of the dura mater.

PMID- 15520836
TI  - Increased production of reactive oxygen species contributes to motor neuron death
      in a compression mouse model of spinal cord injury.
AB  - STUDY DESIGN: Experimental laboratory investigation of the role and pathways of
      reactive oxygen species (ROS)-mediated motor neuron cell death in a mouse model
      of compression spinal cord injury. OBJECTIVES: To analyze ROS-mediated oxidative
      stress propagation and signal transduction leading to motor neuron apoptosis
      induced by compression spinal cord injury. SETTING: University of Louisville
      Health Science Center. METHODS: Adult C57BL/6J mice and transgenic mice
      overexpressing SOD1 were severely lesioned at the lumbar region by compression
      spinal cord injury approach. Fluorescent oxidation, oxidative response gene
      expression and oxidative stress damage markers were used to assay spinal cord
      injury-mediated ROS generation and oxidative stress propagation. Biochemical and
      immunohistochemical analyses were applied to define the ROS-mediated motor neuron
      apoptosis resulted from compression spinal cord injury. RESULTS: ROS production
      was shown to be elevated in the lesioned spinal cord as detected by fluorescent
      oxidation assays. The early oxidative stress response markers, NF-kappaB
      transcriptional activation and c-Fos gene expression, were significantly
      increased after spinal cord injury. Lipid peroxidation and nucleic acid oxidation
      were also elevated in the lesioned spinal cord and motor neurons. Cytochrome c
      release, caspase-3 activation and apoptotic cell death were increased in the
      spinal cord motor neuron cells after spinal cord injury. On the other hand,
      transgenic mice overexpressing SOD1 showed lower levels of steady-state ROS
      production and reduction of motor neuron apoptosis compared to that of control
      mice after spinal cord injury. CONCLUSION: These data together provide direct
      evidence to demonstrate that the increased production of ROS is an early and
      likely causal event that contributes to the spinal cord motor neuron death
      following spinal cord injury. Thus, antioxidants/antioxidant enzyme intervention
      combined with other therapy may provide an effective approach to alleviate spinal
      cord injury-induced motor neuron damage and motor dysfunction.

PMID- 15520837
TI  - Improved functional outcome after spinal cord injury in iNOS-deficient mice.
AB  - STUDY DESIGN: Functional outcome was evaluated following experimental compression
      type spinal cord injury (SCI) in wild-type mice and knockout mice, lacking the
      inducible nitric oxide synthase (iNOS) gene. OBJECTIVES: To evaluate the role of
      the nitric oxide generating enzyme iNOS in SCI. METHODS: The experimental animals
      were subjected to an extradural compression of the thoracic spinal cord.
      Functional outcome was studied during the first 2 weeks post-injury using a
      scoring system for assessment of hind limb motor function. RESULTS: Injury
      resulted in initial paraplegia followed by gradual improvement of motor function
      in most cases. Mice lacking the iNOS gene (iNOS-/-) clearly tended to have a
      better functional outcome than wild-type mice. The difference was significant on
      day 14 after injury. CONCLUSION: In accordance with a few earlier experimental
      studies, showing beneficial effects of pharmacological iNOS inhibition, the
      present report would indicate a destructive influence of iNOS following spinal
      cord trauma.

PMID- 15520838
TI  - A simple methodology to improve AIS-based assessment of recovery after acute
      spinal cord injury.

PMID- 15520840
TI  - A complex series of events in a patient with sacral anterior root stimulator
      (SARS).

PMID- 15520841
TI  - Walking index for spinal cord injury (WISCI): criterion validation.
AB  - STUDY DESIGN: Retrospective examination. OBJECTIVES: To compare the Walking Index
      for Spinal Cord Injury (WISCI) and current scales for their sensitivity to
      walking changes in subjects with a spinal cord lesion (SCL) and further validate
      the WISCI for use in clinical trails. SETTING: A large rehabilitation hospital in
      the center of Italy. PATIENTS AND METHODS: Retrospective review was performed on
      284 patient records with an SCL. Measurements included neurological evaluation
      with Lower Extremity Motor Scores (LEMS) according to the American Spinal Injury
      Association (ASIA) and walking status assessed by Barthel Index (BI (0-15)),
      Rivermead Mobility Index (RMI (three levels)), Functional Independence Measure
      (FIM (1-7)), Spinal Cord Independence Measure (SCIM (0-8)), and WISCI (0-20). The
      WISCI is a 21-level hierarchical scale which incorporates gradations of physical
      assistance and devices required for walking. Improvement in walking is based on
      the change of scores from admission to discharge. Statistical analysis included
      Spearman rank correlation and chi2 test; P<0.05. RESULTS: There was a significant
      positive correlation between WISCI and other scales (WISCI and BI r=0.67,
      P<0.001; WISCI and RMI r=0.67, P<0.001; WISCI and SCIM r=0.97, P<0.001; WISCI and
      FIM r=0.7, P<0.001). The initial ASIA grade was predictive of mobility outcome on
      the WISCI: of the 78 ASIA A patients, only five achieved independent walking
      versus 4/17 ASIA B (P=0.02), 56/109 ASIA C (P<0.001) and 39/44 ASIA D (P<0.001).
      The correlation of LEMS to the WISCI was 0.58 (P<0.001). At discharge, patients
      were distributed into 12 WISCI levels versus four FIM, three BI, two RMI and five
      SCIM levels. The most frequent WISCI levels at discharge were 13 (walker, no
      braces or assistance), 16 (two crutches, no braces or assistance) and 20 (no
      devices or assistance). CONCLUSIONS: Similar correlation between the WISCI and
      the other scales indicates that all these measures address the same concept,
      mobility, which is a measure of concurrent validity. The correlation is not 100%
      because of conceptual differences (the WISCI incorporates gradations of physical
      assistance and devices required for walking while most of the other scales focus
      on burden of care or mobility in the environment). The WISCI is more detailed and
      appears more sensitive to walking recovery than the other scales, as demonstrated
      by our patients' score distribution at discharge. Within each of the most
      frequent WISCI levels (13, 16, 20) LEMS and other walking features varied;
      therefore the scale would benefit from further refinement based on speed,
      distance and energy cost.

PMID- 15520842
TI  - Prevalence of spinal cord injury in Helsinki.
AB  - STUDY DESIGN: Retrospective register-based epidemiological study. OBJECTIVE: To
      estimate the prevalence rate of persons with spinal cord injury (SCI) with
      special reference to ASIA Impairment Grade A-D. SETTING: Helsinki, Finland.
      METHODS: Cases were identified using the registers of the Kapyla Rehabilitation
      Centre, Helsinki University Central Hospital and the local organization for the
      disabled. Local health centres were informed about the study, residential service
      houses were contacted, and announcements were published in patient magazines.
      RESULTS: A regional population was found to have a prevalence rate of 28/100,000
      inhabitants with SCI (ASIA Impairment Scale A-D). CONCLUSION: The prevalence rate
      in this study is consistent with the data published in other Nordic countries.
      SPONSORSHIP: The Finnish Cultural Foundation.

PMID- 15520843
TI  - The catechol-O-methyltransferase Val108/158Met polymorphism affects short-term
      treatment response to mirtazapine, but not to paroxetine in major depression.
AB  - The catechol-O-methyltransferase (COMT) is a major degrading enzyme in the
      metabolic pathways of catecholaminergic neurotransmitters such as dopamine and
      norepinephrine. This study investigated whether the functionally relevant
      Val(108/158)Met gene variant is associated with differential antidepressant
      response to mirtazapine and/or paroxetine in 102 patients with major depression
      (DSM-IV criteria) participating in a randomized clinical trial with both drugs.
      In patients treated with mirtazapine, but not paroxetine, allelic variations in
      the COMT gene were associated with differential response. COMT(VAL/VAL) and
      COMT(VAL/MET) genotype carriers showed a better response than COMT(MET/MET)
      bearing patients in the mirtazapine group. Moreover, carriers of the
      COMT(VAL/VAL) or COMT(VAL/MET) genotype had significantly greater HAMD-17
      (Hamilton Rating Scale for Depression 17 item version) score reductions than
      COMT(MET/MET) homozygotes from week 2 to 6, respectively, in the mirtazapine
      group. Time course of response and antidepressant efficacy of mirtazapine, but
      not paroxetine, seem to be influenced in a clinically relevant manner by this
      allelic variation within the COMT gene.

PMID- 15520844
TI  - Lost gold: the decline of the academic mission in US medical schools.
AB  - Medical education needs to be redesigned so that it is an equally shared
      responsibility of clinicians and physician-scientists, with greatly enhanced
      opportunities for student-faculty bonding. Traditional departments and divisions
      must be restructured to provide more thoughtful and effective support for
      academic clinicians and physician-scientists. Existing infrastructure should be
      improved so that in exchange for the commitment of time and effort for teaching,
      the faculty members receive tangible services from their institutions (e.g.,
      information technology that actually saves time, state-of-the art teaching aids
      that are user friendly, streamlined administrative oversight to avoid duplicate
      submissions to regulatory offices, more helpful grant management and accounting).

PMID- 15520845
TI  - Resistance rising.

PMID- 15520846
TI  - Embryonic death and the creation of human embryonic stem cells.
AB  - The creation of human embryonic stem cells through the destruction of a human
      embryo pits the value of a potential therapeutic tool against that of an early
      human life. This contest of values has resulted in a polarized debate that
      neglects areas of common interest and perspective. We suggest that a common
      ground for pursuing research on human embryonic stem cells can be found by
      reconsidering the death of the human embryo and by applying to this research the
      ethical norms of essential organ donation.

PMID- 15520847
TI  - How does blood glucose control with insulin save lives in intensive care?
AB  - Patients requiring prolonged intensive care are at high risk for multiple organ
      failure and death. Insulin resistance and hyperglycemia accompany critical
      illness, and the severity of this "diabetes of stress" reflects the risk of
      death. Recently it was shown that preventing hyperglycemia with insulin
      substantially improves outcome of critical illness. This article examines some
      potential mechanisms underlying prevention of glucose toxicity as well as the
      effects of insulin independent of glucose control. Unraveling the molecular
      mechanisms will provide new insights into the pathogenesis of multiple organ
      failure and open avenues for novel therapeutic strategies.

PMID- 15520848
TI  - An integrated view of suppressor T cell subsets in immunoregulation.
AB  - The immune system evolved to protect organisms from a virtually infinite variety
      of disease-causing agents but to avoid harmful responses to self. Because immune
      protective mechanisms include the elaboration of potent inflammatory molecules,
      antibodies, and killer cell activation--which together can not only destroy
      invading microorganisms, pathogenic autoreactive cells, and tumors, but also
      mortally injure normal cells--the immune system is inherently a "double-edged
      sword" and must be tightly regulated. Immune response regulation includes
      homeostatic mechanisms intrinsic to the activation and differentiation of antigen
      triggered immunocompetent cells and extrinsic mechanisms mediated by suppressor
      cells. This review series will focus on recent advances indicating that distinct
      subsets of regulatory CD4+ and CD8+ T cells as well as NK T cells control the
      outgrowth of potentially pathogenic antigen-reactive T cells and will highlight
      the evidence that these suppressor T cells may play potentially important
      clinical roles in preventing and treating immune-mediated disease. Here we
      provide a historical overview of suppressor cells and the experimental basis for
      the existence of functionally and phenotypically distinct suppressor subsets.
      Finally, we will speculate on how the distinct suppressor cell subsets may
      function in concert to regulate immune responses.

PMID- 15520849
TI  - CD4+ Tregs and immune control.
AB  - Recent years have seen Tregs become a popular subject of immunological research.
      Abundant experimental data have now confirmed that naturally occurring CD25+CD4+
      Tregs in particular play a key role in the maintenance of self tolerance, with
      their dysfunction leading to severe or even fatal immunopathology. The sphere of
      influence of Tregs is now known to extend well beyond just the maintenance of
      immunological tolerance and to impinge on a host of clinically important areas
      from cancer to infectious diseases. The identification of specific molecular
      markers in both human and murine immune systems has enabled the unprecedented
      investigation of these cells and should prove key to ultimately unlocking their
      clinical potential.

PMID- 15520850
TI  - Qa-1 restriction of CD8+ suppressor T cells.
AB  - There is increasing evidence that the immune response can be inhibited by several
      T cell subsets, including NK T cells, CD25+CD4+ T cells, and a subpopulation of
      CD8+ T cells. Animal model studies of multiple sclerosis have suggested an
      important role for suppressor CD8+ T cells in protection against disease
      recurrence and exacerbation. The molecular lynchpin of CD8+ suppressive activity
      is the murine MHC molecule Qa-1, termed HLA-E in humans. Here we summarize
      findings from work on Qa-1 that have begun to delineate suppressor CD8+ T cells
      and their mechanisms of action in the context of self tolerance and autoimmune
      disease.

PMID- 15520851
TI  - Homeostatic control of immunity by TCR peptide-specific Tregs.
AB  - Regulation of the immune response is a multifaceted process involving lymphocytes
      that function to maintain both self tolerance as well as homeostasis following
      productive immunity against microbes. There are 2 broad categories of Tregs that
      function in different immunological settings depending upon the context of
      antigen exposure and the nature of the inflammatory response. During massive
      inflammatory conditions such as microbial exposure in the gut or tissue
      transplantation, regulatory CD4+CD25+ Tregs broadly suppress priming and/or
      expansion of polyclonal autoreactive responses nonspecifically. In other immune
      settings where initially a limited repertoire of antigen-reactive T cells is
      activated and expanded, TCR-specific negative feedback mechanisms are able to
      achieve a fine homeostatic balance. Here I will describe experimental evidence
      for the existence of a Treg population specific for determinants that are derived
      from the TCR and are expressed by expanding myelin basic protein-reactive T cells
      mediating experimental autoimmune encephalomyelitis, an animal prototype for
      multiple sclerosis. These mechanisms ensure induction of effective but
      appropriately limited responses against foreign antigens while preventing
      autoreactivity from inflicting escalating damage. In contrast to CD25+ Tregs,
      which are most efficient at suppressing priming or activation, these specific
      Tregs are most efficient in controlling T cells following their activation.

PMID- 15520852
TI  - Tregs in T cell vaccination: exploring the regulation of regulation.
AB  - T cell vaccination (TCV) activates Tregs of 2 kinds: anti-idiotypic (anti-id) and
      anti-ergotypic (anti-erg). These regulators furnish a useful view of the
      physiology of T cell regulation of the immune response. Anti-id Tregs recognize
      specific effector clones by their unique TCR CDR3 peptides; anti-id networks of
      CD4+ and CD8+ Tregs have been described in detail. Here we shall focus on anti
      erg T regulators. Anti-erg T cells, unlike anti-id T cells, do not recognize the
      clonal identity of effector T cells; rather, anti-erg T cells recognize the state
      of activation of target effector T cells, irrespective of their TCR specificity.
      We consider several features of anti-erg T cells: their ontogeny, subset markers,
      and target ergotope molecules; mechanisms by which they regulate other T cells;
      mechanisms by which they get regulated; and therapeutic prospects for anti-erg
      upregulation and downregulation.

PMID- 15520853
TI  - Inflammatory bowel disease reveals the kinase activity of KSR1.
AB  - Kinase suppressor of Ras-1 (KSR1) is a recently identified member of the EGFR-Ras
      Raf-1-MAPK signaling pathway. A new study demonstrates that KSR1 protects
      intestinal epithelium from TNF-alpha-induced apoptosis, abrogating inflammatory
      bowel disease (IBD). Since its discovery, there has been disagreement as to
      whether KSR1 possesses intrinsic kinase activity. Using transgenic mouse models
      and genetically modified mouse colon epithelial cells, Polk and coworkers show
      that the kinase activity of KSR1 is off in normal colon epithelial cells,
      becoming activated only at the onset of IBD. They also provide strong evidence
      that KSR1 kinase activity is essential for anti-apoptotic protection of the
      intestinal epithelium. These new data in support of KSR1 as a kinase highlight an
      ongoing debate as to whether KSR1 does indeed serve as a specific kinase in
      transphosphorylating and transactivating c-Raf-1 toward MEK1.

PMID- 15520854
TI  - p16 and ARF: activation of teenage proteins in old age.
AB  - Cellular senescence induced by different stresses and telomere shortening appears
      to play an important role in the aging process. The products of the INK4a/ARF
      locus--p16INK4a and ARF--arrest cell proliferation at the senescence stage by
      exerting their effects on retinoblastoma protein- and p53-mediated responsive
      pathways. A study in this issue of the JCI provides experimental evidence of a
      specific upregulation of these cell cycle inhibitors in a variety of organs
      during mammalian aging.

PMID- 15520855
TI  - Developing DNA vaccines that call to dendritic cells.
AB  - DNA vaccination is a novel immunization strategy that has great potential for the
      development of vaccines and immune therapeutics. This strategy has been highly
      effective in mice, while less immunogenic in nonhuman primates and humans.
      Enhancing DNA vaccine potency remains a challenge. It is likely that APCs, and
      especially DCs, play a paramount role in the presentation of vaccine antigen to
      the immune system. A new study reports the synergistic recruitment, expansion,
      and activation of DCs in vivo in a mouse model through covaccination with
      plasmids encoding macrophage inflammatory protein-1alpha (MIP-1alpha), fms-like
      tyrosine kinase 3 ligand (Flt3L), and the DNA vaccine. Such cooperative
      strategies delivering vaccine in a single, simple platform result in improved
      cellular immunity in vivo, including enhanced tetramer responses and IFN-gamma
      secretion by antigen-specific cells.

PMID- 15520856
TI  - Do DNA sequence variants in ABCA1 contribute to HDL cholesterol levels in the
      general population?
AB  - HDL has a key role in reverse cholesterol transport, mobilizing cholesterol from
      the peripheral tissues to liver. In this process, the ABC transporter A1 (ABCA1)
      protein controls the efflux of intracellular cholesterol to apoAI, the major
      apolipoprotein of HDL. Since ABCA1 mutations were discovered to cause Tangier
      disease, a rare recessive HDL deficiency, it has been speculated that sequence
      variants in ABCA1 might also contribute to variations in plasma HDL cholesterol
      levels in the general population. A new study provides genetic evidence
      supporting this hypothesis.

PMID- 15520857
TI  - Genetic ablation of Nrf2 enhances susceptibility to cigarette smoke-induced
      emphysema in mice.
AB  - Although inflammation and protease/antiprotease imbalance have been postulated to
      be critical in cigarette smoke-induced (CS-induced) emphysema, oxidative stress
      has been suspected to play an important role in chronic obstructive pulmonary
      diseases. Susceptibility of the lung to oxidative injury, such as that
      originating from inhalation of CS, depends largely on its upregulation of
      antioxidant systems. Nuclear factor, erythroid-derived 2, like 2 (Nrf2) is a
      redox-sensitive basic leucine zipper protein transcription factor that is
      involved in the regulation of many detoxification and antioxidant genes.
      Disruption of the Nrf2 gene in mice led to earlier-onset and more extensive CS
      induced emphysema than was found in wild-type littermates. Emphysema in Nrf2
      deficient mice exposed to CS for 6 months was associated with more pronounced
      bronchoalveolar inflammation; with enhanced alveolar expression of 8-oxo-7,8
      dihydro-2'-deoxyguanosine, a marker of oxidative stress; and with an increased
      number of apoptotic alveolar septal cells--predominantly endothelial and type II
      epithelial cells--as compared with wild-type mice. Microarray analysis identified
      the expression of nearly 50 Nrf2-dependent antioxidant and cytoprotective genes
      in the lung that may work in concert to counteract CS-induced oxidative stress
      and inflammation. The responsiveness of the Nrf2 pathway may act as a major
      determinant of susceptibility to tobacco smoke-induced emphysema by upregulating
      antioxidant defenses and decreasing lung inflammation and alveolar cell
      apoptosis.

PMID- 15520858
TI  - Semaphorin 3F, a chemorepulsant for endothelial cells, induces a poorly
      vascularized, encapsulated, nonmetastatic tumor phenotype.
AB  - Melanoma is the most lethal skin cancer. Most deaths from melanoma result from
      metastases. Semaphorins have been shown to inhibit neuronal and endothelial cell
      migration, but the effects of semaphorins on tumor metastasis have not been
      documented. We found that semaphorin 3F (SEMA3F) was markedly downregulated in
      highly metastatic human cell lines in vitro and in vivo, which suggested that it
      may be a metastasis inhibitor. Metastatic human melanoma cells were transfected
      with SEMA3F and implanted into mice; the resultant tumors did not metastasize.
      Rather, the primary tumors resembled benign nevi characterized by large areas of
      apoptosis, diminished vascularity, inhibition of hyperplasia in overlying
      epidermal cells, and encapsulated tumor borders delineated by thick layers of
      fibroblasts and collagen matrix. This phenotype is in stark contrast to highly
      invasive, vascular mock-transfected tumors. In vitro, tumor cells expressing
      SEMA3F had a diminished capacity to adhere and migrate on fibronectin. Consistent
      with semaphorin-mediated chemorepulsion of neurons, tumor cells expressing SEMA3F
      were chemorepulsive for vascular and lymphatic endothelial cells expressing
      neuropilin-2 (NRP2), a novel mechanism for a tumor angiogenesis inhibitor. The
      repulsive activity was abrogated by NRP2 RNA interference. Together these results
      indicate that SEMA3F is a potent metastasis inhibitor that targets both tumor and
      stromal cells and raise the possibility of SEMA3F having therapeutic potential.

PMID- 15520859
TI  - Kinase suppressor of Ras-1 protects intestinal epithelium from cytokine-mediated
      apoptosis during inflammation.
AB  - TNF plays a pathogenic role in inflammatory bowel diseases (IBDs), which are
      characterized by altered cytokine production and increased intestinal epithelial
      cell apoptosis. In vitro studies suggest that kinase suppressor of Ras-1 (KSR1)
      is an essential regulatory kinase for TNF-stimulated survival pathways in
      intestinal epithelial cell lines. Here we use a KSR1-deficient mouse model to
      study the role of KSR1 in regulating intestinal cell fate during cytokine
      mediated inflammation. We show that KSR1 and its target signaling pathways are
      activated in inflamed colon mucosa. Loss of KSR1 increases susceptibility to
      chronic colitis and TNF-induced apoptosis in the intestinal epithelial cell.
      Furthermore, disruption of KSR1 expression enhances TNF-induced apoptosis in
      mouse colon epithelial cells and is associated with a failure to activate
      antiapoptotic signals including Raf-1/MEK/ERK, NF-kappaB, and Akt/protein kinase
      B. These effects are reversed by WT, but not kinase-inactive, KSR1. We conclude
      that KSR1 has an essential protective role in the intestinal epithelial cell
      during inflammation through activation of cell survival pathways.

PMID- 15520860
TI  - Mitochondrial remodeling in adipose tissue associated with obesity and treatment
      with rosiglitazone.
AB  - Adipose tissue plays a central role in the control of energy homeostasis through
      the storage and turnover of triglycerides and through the secretion of factors
      that affect satiety and fuel utilization. Agents that enhance insulin
      sensitivity, such as rosiglitazone, appear to exert their therapeutic effect
      through adipose tissue, but the precise mechanisms of their actions are unclear.
      Rosiglitazone changes the morphological features and protein profiles of
      mitochondria in 3T3-L1 adipocytes. To examine the relevance of these effects in
      vivo, we studied white adipocytes from ob/ob mice during the development of
      obesity and after treatment with rosiglitazone. The levels of approximately 50%
      of gene transcripts encoding mitochondrial proteins were decreased with the onset
      of obesity. About half of those genes were upregulated after treatment with
      rosiglitazone, and this was accompanied by an increase in mitochondrial mass and
      changes in mitochondrial structure. Functionally, adipocytes from rosiglitazone
      treated mice displayed markedly enhanced oxygen consumption and significantly
      increased palmitate oxidation. These data reveal mitochondrial remodeling and
      increased energy expenditure in white fat in response to rosiglitazone treatment
      in vivo and suggest that enhanced lipid utilization in this tissue may affect
      whole-body energy homeostasis and insulin sensitivity.

PMID- 15520861
TI  - A viral epitope that mimics a self antigen can accelerate but not initiate
      autoimmune diabetes.
AB  - We document here that infection of prediabetic mice with a virus expressing an H
      2Kb-restricted mimic ligand to a self epitope present on beta cells accelerates
      the development of autoimmune diabetes. Immunization with the mimic ligand
      expanded autoreactive T cell populations, which was followed by their trafficking
      to the islets, as visualized in situ by tetramer staining. In contrast, the mimic
      ligand did not generate sufficient autoreactive T cells in naive mice to initiate
      disease. Diabetes acceleration did not occur in H-2Kb-deficient mice or in mice
      tolerized to the mimic ligand. Thus, arenavirus-expressed mimics of self antigens
      accelerate a previously established autoimmune process. Sequential heterologous
      viral infections might therefore act in concert to precipitate clinical
      autoimmune disease, even if single exposure to a viral mimic does not always
      cause sufficient tissue destruction.

PMID- 15520862
TI  - Ink4a/Arf expression is a biomarker of aging.
AB  - The Ink4a/Arf locus encodes 2 tumor suppressor molecules, p16INK4a and Arf, which
      are principal mediators of cellular senescence. To study the links between
      senescence and aging in vivo, we examined Ink4a/Arf expression in rodent models
      of aging. We show that expression of p16INK4a and Arf markedly increases in
      almost all rodent tissues with advancing age, while there is little or no change
      in the expression of other related cell cycle inhibitors. The increase in
      expression is restricted to well-defined compartments within each organ studied
      and occurs in both epithelial and stromal cells of diverse lineages. The age
      associated increase in expression of p16INK4a and Arf is attenuated in the
      kidney, ovary, and heart by caloric restriction, and this decrease correlates
      with diminished expression of an in vivo marker of senescence, as well as
      decreased pathology of those organs. Last, the age-related increase in Ink4a/Arf
      expression can be independently attributed to the expression of Ets-1, a known
      p16INK4a transcriptional activator, as well as unknown Ink4a/Arf coregulatory
      molecules. These data suggest that expression of the Ink4a/Arf tumor suppressor
      locus is a robust biomarker, and possible effector, of mammalian aging.

PMID- 15520863
TI  - Imatinib mesylate inhibits the profibrogenic activity of TGF-beta and prevents
      bleomycin-mediated lung fibrosis.
AB  - Idiopathic pulmonary fibrosis is a progressive and fatal fibrotic disease of the
      lungs with unclear etiology. Prior efforts to treat idiopathic pulmonary fibrosis
      that focused on anti-inflammatory therapy have not proven to be effective. Recent
      insight suggests that the pathogenesis is mediated through foci of dysregulated
      fibroblasts driven by profibrotic cytokine signaling. TGF-beta and PDGF are 2 of
      the most potent of these cytokines. In the current study, we investigated the
      role of TGF-beta-induced fibrosis mediated by activation of the Abelson (Abl)
      tyrosine kinase. Our data indicate that fibroblasts respond to TGF-beta by
      stimulating c-Abl kinase activity independently of Smad2/3 phosphorylation or
      PDGFR activation. Moreover, inhibition of c-Abl by imatinib prevented TGF-beta
      induced ECM gene expression, morphologic transformation, and cell proliferation
      independently of any effect on Smad signaling. Further, using a mouse model of
      bleomycin-induced pulmonary fibrosis, we found a significant inhibition of lung
      fibrosis by imatinib. Thus, Abl family members represent common targets for the
      modulation of profibrotic cytokine signaling.

PMID- 15520864
TI  - Mast cell-derived angiopoietin-1 plays a critical role in the growth of plasma
      cell tumors.
AB  - Multiple myeloma in humans is frequently associated with mast cell infiltration
      and neovascularization, which correlate directly with disease severity, but the
      mechanisms underlying this relationship remain unclear. Here, we report that
      primary murine mast cells express angiopoietin-1 (Ang-1) and low levels of VEGF-A
      but not Ang-2 and that 2 established murine plasmacytoma cell lines express high
      levels of VEGF-A but little or no Ang-1 or Ang-2. An in vivo angiogenesis assay
      using extracellular matrix components shows that mast cells and plasmacytoma
      cells, together, promote marked neovascularization composed of dilated vessels,
      which is prevented by neutralization of VEGF-A and Ang-1 but is only partially
      reduced by neutralization of either VEGF-A or Ang-1. Mast cells within
      extracellular matrix components express Ang-1, and recombinant Ang-1 together
      with plasmacytoma cells promotes extracellular matrix neovascularization similar
      to that induced by mast cells. A transplantation assay shows that primary mast
      cells accelerate tumor growth by established plasmacytoma cell lines and that
      neutralization of Ang-1 alone or with VEGF-A reduces significantly the growth of
      plasmacytomas containing mast cells. These results demonstrate that mast cell
      derived Ang-1 promotes the growth of plasmacytomas by stimulating
      neovascularization and provide further evidence supporting a causal relationship
      between inflammation and tumor growth.

PMID- 15520865
TI  - c-Cbl-deficient mice have reduced adiposity, higher energy expenditure, and
      improved peripheral insulin action.
AB  - Casitas b-lineage lymphoma (c-Cbl) is an E3 ubiquitin ligase that has an
      important role in regulating the degradation of cell surface receptors. In the
      present study we have examined the role of c-Cbl in whole-body energy
      homeostasis. c-Cbl-/- mice exhibited a profound increase in whole-body energy
      expenditure as determined by increased core temperature and whole-body oxygen
      consumption. As a consequence, these mice displayed a decrease in adiposity,
      primarily due to a reduction in cell size despite an increase in food intake.
      These changes were accompanied by a significant increase in activity (2- to 3
      fold). In addition, c-Cbl-/- mice displayed a marked improvement in whole-body
      insulin action, primarily due to changes in muscle metabolism. We observed
      increased protein levels of the insulin receptor (4-fold) and uncoupling protein
      3 (2-fold) in skeletal muscle and a significant increase in the phosphorylation
      of AMP-activated protein kinase and acetyl-CoA carboxylase. These findings
      suggest that c-Cbl plays an integral role in whole-body fuel homeostasis by
      regulating whole-body energy expenditure and insulin action.

PMID- 15520866
TI  - Recruitment and expansion of dendritic cells in vivo potentiate the
      immunogenicity of plasmid DNA vaccines.
AB  - DCs are critical for priming adaptive immune responses to foreign antigens.
      However, the utility of harnessing these cells in vivo to optimize the
      immunogenicity of vaccines has not been fully explored. Here we investigate a
      novel vaccine approach that involves delivering synergistic signals that both
      recruit and expand DC populations at the site of antigen production.
      Intramuscular injection of an unadjuvanted HIV-1 envelope (env) DNA vaccine
      recruited few DCs to the injection site and elicited low-frequency, env-specific
      immune responses in mice. Coadministration of plasmids encoding the chemokine
      macrophage inflammatory protein-1alpha (MIP-1alpha) and the DC-specific growth
      factor fms-like tyrosine kinase 3 ligand with the DNA vaccine resulted in the
      recruitment, expansion, and activation of large numbers of DCs at the site of
      inoculation. Consistent with these findings, coadministration of these plasmid
      cytokines also markedly augmented DNA vaccine---elicited cellular and humoral
      immune responses and increased protective efficacy against challenge with
      recombinant vaccinia virus. These data suggest that the availability of mature
      DCs at the site of inoculation is a critical rate-limiting factor for DNA vaccine
      immunogenicity. Synergistic recruitment and expansion of DCs in vivo may prove a
      practical strategy for overcoming this limitation and potentiating immune
      responses to vaccines as well as other immunotherapeutic strategies.

PMID- 15520867
TI  - Genetic variation in ABC transporter A1 contributes to HDL cholesterol in the
      general population.
AB  - Homozygosity for mutations in ABC transporter A1 (ABCA1) causes Tangier disease,
      a rare HDL-deficiency syndrome. Whether heterozygosity for genetic variation in
      ABCA1 also contributes to HDL cholesterol (HDL-C) levels in the general
      population is presently unclear. We determined whether mutations or single
      nucleotide polymorphisms (SNPs) in ABCA1 were overrepresented in individuals with
      the lowest 1% (n=95) or highest 1% (n=95) HDL-C levels in the general population
      by screening the core promoter and coding region of ABCA1. For all nonsynonymous
      SNPs identified, we determined the effect of genotype on lipid traits in 9,259
      individuals from the general population. Heterozygosity for ABCA1 mutations was
      identified in 10% of individuals with low HDL-C only. Three of 6 nonsynonymous
      SNPs (V771M, V825I, and R1587K) were associated with increases or decreases in
      HDL-C in women in the general population and some with consistent trends in men,
      determined as isolated single-site effects varying only at the relevant SNP.
      Finally, these results were consistent over time. In conclusion, we show that at
      least 10% of individuals with low HDL-C in the general population are
      heterozygous for mutations in ABCA1 and that both mutations and SNPs in ABCA1
      contribute to HDL-C levels in the general population.

PMID- 15520868
TI  - Mice lacking the syndecan-3 gene are resistant to diet-induced obesity.
AB  - The accurate matching of caloric intake to caloric expenditure involves a complex
      system of peripheral signals and numerous CNS neurotransmitter systems. Syndecans
      are a family of membrane-bound heparan sulfate proteoglycans that modulate ligand
      receptor interactions. Syndecan-3 is heavily expressed in several areas of the
      brain, including hypothalamic nuclei, which are known to regulate energy balance.
      In particular, syndecans have been implicated in modulation of the activity of
      the melanocortin system, which potently regulates energy intake, energy
      expenditure, and peripheral glucose metabolism. Our data demonstrate that
      syndecan-3-null mice have reduced adipose content compared with wild-type mice.
      On a high-fat diet, syndecan-3-null male and female mice exhibited a partial
      resistance to obesity due to reduced food intake in males and increased energy
      expenditure in females relative to that of wild-type mice. As a result, syndecan
      3-null mice on a high-fat diet accumulated less adipose mass and showed improved
      glucose tolerance compared with wild-type controls. The data implicate syndecan-3
      in the regulation of body weight and suggest that inhibition of syndecan-3 may
      provide a therapeutic approach for the treatment of obesity resulting from
      exposure to high-fat diets.

PMID- 15520869
TI  - [The role of DNA adducts in smoking-related carcinogenesis].
AB  - Epidemiological studies indicate a close association between smoking and cancer.
      Biological activity of many chemical carcinogens and of their metabolites is
      induced by covalent binding of their reactive derivatives to DNA, which
      consequently causes mutations in critical genes. Carcinogen-DNA adducts formed by
      exposure to tobacco smoke have a key role in the initiation of various types of
      cancer including lung cancer. Presence of tobacco smoke-related carcinogen-DNA
      adducts in various tissues of smokers proves the DNA damaging effect of smoking.
      DNA adducts are important biomarkers for the biomonitoring of human genotoxic
      exposures to tobacco smoke. The paper gives a short overview on the role of
      smoking-related DNA adducts in carcinogenesis.

PMID- 15520870
TI  - [Proteoglycans in the liver].
AB  - Proteoglycans are macromolecules formed by a protein core to which sugar chains
      are covalently attached. They are present on the cell surface and in the ECM of
      living things. In normal liver syndecan-1 is the dominant transmembrane
      proteoglycan, trace amounts of ECM proteoglycans are in the stromal components.
      The amounts of proteoglycans we studied increase in liver cirrhosis. In liver
      cancer abnormal localization of syndecan-1 and stroma rich in agrin was
      characteristic. The core proteins as well as the sugar chains of proteoglycans
      interact with and modulate the effect of regulatory factors. This implies that
      structural alterations of proteoglycans contribute to the development of
      malignant phenotype. Heparan sulfate chains of liver cancer are undersulfated
      with decreased or altered biological activity. Their binding capacity for
      transcription factor decreases, and they do not inhibit topoisomerase I enzyme.
      Truncated form of syndecan-1 lacking the extracellular domain of the molecule
      induces differentiation of hepatoma cell line and inhibits the shedding of
      syndecan-1. This phenomenon calls attention to the importance of syndecan-1
      shedding in the regulation of cell behavior.

PMID- 15520871
TI  - [The occurrence and significance of apoptosis in tumors].
AB  - Decreased apoptotic activity in precancerous lesions and in malignant tumors has
      largely been prejudiced. Results of studies performed in the last years showed
      that this suggestion is correct only in certain types of tumors. Data have been
      revealed on higher apoptotic activity in poorly differentiated tumors, whereas in
      well-differentiated neoplasms this activity is relatively low. At the same time,
      cytostatic or hormonal treatment of well-differentiated tumors result in a
      considerable elevation of the apoptotic index. The author considers the
      inducibility of apoptosis as a predictive factor regarding the efficacy of
      therapy in case of prostate carcinoma, colon carcinoma and acute lymphoid
      leukemia. This statement is less applicable to breast cancer or mesopharyngeal
      carcinoma. Very low apoptotic activity was observed in neuroblastomas, follicular
      adenomas, as well as follicular and papillary carcinomas of the thyroid gland,
      and adenomas of the parathyroid gland. Expression of genes influencing apoptosis,
      such as bcl2, p53, and bax, may rather be of importance from the point of view of
      histological differential diagnosis.

PMID- 15520872
TI  - [Antisense oligonucleotides with antitumor activity].
AB  - Antisense oligonucleotides (AONs) provide an efficient approach for developing
      target-selective anticancer drugs, because they can inhibit gene expression
      sequence specifically. To improve the therapeutic effenciency of AONs, two new
      types of the compounds have been developed. The first group of antisense
      oligodeoxynucleotides investigated contains base modified nucleotide units.
      Incorporation of 5-substituted pyrimidines into AONs increases cell membrane
      permeability (a), duplex stability (b), and nuclease resistance (c). These
      properties were studied using a large number of model oligonucleotides. The
      application of 5-(1-hexynyl)dU has been found to be the best modification.
      Application of MMP-9 collagenase inhibitor oligonucleotides (potential metastasis
      inhibitors) containing these nucleotide units instead of thymidines increased the
      collagenase inhibition potency by one order of magnitude compared to that of
      parental oligonucleotide including thymine bases. The second group of the
      compounds investigated represents a new type of antisense oligonucleotide
      synthesized by the antisense directed prodrug therapy (ADPT) conception.
      According to this principle, a telomerase inhibitor AON was conjugated with 5
      fluoro-2'-deoxyuridine (FdU) and oligo-FdUs by phosphodiester bond at the 3'
      terminus. The antitumor activities of conjugates in comparison with that of FdU
      were tested in HT1080 human fibrosarcoma and HT29 human colon adenocarcinoma cell
      lines. In HT29 cell culture the antiproliferative activity of prodrugs
      significantly increased with increasing length of the 3'-(FdU)n tail. The
      conjugate with one FdU unit was about 5 times, while the AON-(FdU)3 analogue was
      almost 19 times more active than FdU. Antitumor activity of the prodrug
      containing six FdU units was extremely high (relative efficiency = 26.6),
      therefore, in vivo testing of this analogue seems to be reasonable and promising.
      Antiproliferative activity of (FdU)n conjugated with a telomerase inhibitor
      increased by 5-13 times in HT1080 cells as compared to FdU administered in
      nucleoside form.

PMID- 15520873
TI  - [Special function of deoxycytidine kinase (dCK) in the activation of
      chemotherapeutic nucleoside analogs and in the inhibition of cell proliferation].
AB  - Deoxycytidine kinase (dCK) plays a central role in the deoxynucleoside salvage
      processes, phosphorylating dC, dA, and dG to their monophosphates. In mammalian
      cells, the major source of dTTP comes also from dC via dCMP deaminase. Moreover,
      based on its broad substrate specificity, this enzyme is responsible for the
      activation of several nucleoside analogues of therapeutical importance,
      influencing the sensitivity of malignant tissues towards chemotherapy. The
      expression of dCK is highest in different lymphoid cells/tissues, in embryonic
      cells and in most malignant cells (2, 7, 13-15, 18). The activity of dCK is not
      cell cycle-regulated. In contrast to this, dCK activity was found to be elevated
      several fold upon short-term treatments of normal human lymphocytes with
      therapeutic nucleoside analogs, and other genotoxic agents as well as by DNA
      damaging agents including the DNA polymerase inhibitor aphidicolin, the
      topoisomerase II inhibitor etoposide and gamma-irradiation, which might be a
      potentially important phenomenon with respect to the clinical practice, too.
      These findings indicated that the main trigger of activation could be the damaged
      DNA itself, and the biological relevance might be to supply the dNTPs for the
      enhanced DNA repair. Activation of dCK was paralleled by elevated levels of
      intracellular dATP, raising the possibility that dCK activation is linked to the
      induction of apoptosis. With regard to the mechanism of enzyme activation, no
      changes were found in the protein and mRNA levels of dCK upon stimulation, while
      the activation process was calcium dependent and comprised a protein
      phosphorylation step. A positive correlation was found between the enzymatic
      activity and the native immunoreactivity of dCK, strongly arguing that dCK
      undergoes a conformational change during activation, which results in the
      formation of a catalytically more active steric structure (8-11, 22, 26, 32-34,
      35, 36).

PMID- 15520874
TI  - [Heparin inhibits metastatization of experimental melanoma].
AB  - Heparin treatment, at human equivalent doses, modulates coagulation parameters in
      mice similarly to the human situation. Heparins were tested in various melanoma
      metastasis models for their antimetastatic activity. Heparins were active against
      melanoma metastasis without influencing the primary tumor. Tumor cell-induced
      platelet aggregation was not the primary target of heparins, since melanoma cells
      were not active in this respect. Our results support the notion that heparins
      have antimetastatic activity.

PMID- 15520875
TI  - [Potentiation of 5-fluorouracil efficacy. Molecular mechanisms playing a role in
      the cytotoxic action of 5-fluorouracil and 5-ethyl-2'-deoxyuridine (EUdR)
      combination].
AB  - Pharmacologic modulation of 5-fluorouracil (5-FU) metabolism provides a
      possibility for the enhancement of its clinical efficacy. AIM: The purpose of the
      present work was to study the effect of 5-ethyl-2'-deoxyuridine (EUdR), a potent
      5-FU modulator, on different molecular mechanisms, influenced by 5-FU itself, and
      to obtain further data about the mode of action of the combination. MATERIALS AND
      METHODS: SW620 cell line was used for the experiments. Cytotoxicity was studied
      by MTT test, cell kinetic changes by FACStar flow cytometer, apoptosis by
      fluorescent microscope after staining the cells with acridine orange and ethydium
      bromide, DNA fragmentation by PAGE electrophoresis after RNase and proteinase-K
      digestion, thymidine incorporation with 3H-thymidine, p53 and PCNA protein
      expression by Western blotting. RESULTS: The cytotoxicity of 5-FU was potentiated
      dose dependently by EUdR. One hundred muM concentration of EUdR resulted in a 40%
      decrease of the IC50 value of 5-FU. Cell cycle arrest in the G2/M transition
      phase was most pronounced after combined treatment with 5-FU+EUdR. EUdR
      potentiated the incorporation of 3Hthymidine into DNA. In addition to the
      increase of apoptosis rate, the expression of p53 protein, caused by 5-FU was
      further potentiated by UdR. CONCLUSION: This study demonstrated a potential novel
      approach to increase the efficacy of 5-FU by EUdR, which incorporated two
      complementary molecular actions, the selective modulation of TS inhibition and
      potentiation of the p53 protein expression, consequently leading to an increase
      in the apoptotic rate.

PMID- 15520876
TI  - [The clinical importance of methylenetetrahydrofolate reductase (MTHFR) C677T
      polymorphism in the 5-fluoropyrimidine-based therapy of metastatic colorectal
      tumours].
AB  - The authors investigated the methylenetetrahydrofolate reductase (MTHFR) C677T
      polymorphism in 101 metastatic colorectal cancer patients treated with 5
      fluoropyrimidine-based therapy and in 196 healthy individuals by PCR-RFLP method.
      There was no significant difference in genotype distribution of patients and
      healthy controls, and between subgroups investigated according to clinical
      parameters (age, gender, tumor location, grade and treatment type). However,
      after a 3-30 (median 18.5) months follow-up the survival of patients with T
      allele proved to be better than that of patients with wild type (CC) genotype
      (p=0.036). In case of CT and TT genotypes the survival of patients receiving only
      first line therapy was significantly shorter than that of patients receiving more
      lines of treatment (p=0.015). Determination of MTHFR C677T polymorphism has
      prognostic value in case of patients with metastatic colorectal cancer receiving
      5-fluoropyrimidine-based therapy, and may help in designing the individual
      (group) tailored therapy.

PMID- 15520877
TI  - [Assessment of prognostic factors in common ovarian tumors of varying
      malignancy].
AB  - OBJECTIVE: The outcome and prognosis of apparently similar cases of epithelial
      ovarian cancers with the same histology and stage is highly variable. The
      objective was to compare survival and prognostic factors of patients treated at
      the 1st Department of Obstetrics and Gynecology of Semmelweis University between
      1993-2003 with the similar data of the 25th Annual Report on the Results of
      Treatment in Gynecological Cancer of FIGO. In addition, the aim was to assess the
      prognostic value of MMP activities and fibronectin concentration in ovarian
      tumour patients. METHODS: The 25th Annual Report of FIGO included 5694 patients
      with ovarian tumours from 32 countries diagnosed and treated between 1995 and
      1998. Hungary did not participate in this report. Between 1993 and 2003, 180
      patients with common epithelial ovarian tumours had been treated at the 1st
      Department of Obstetrics and Gynecology of Semmelweis University. Treatment and
      survival data derived from medical record review and from the Population Register
      Office. In order to compare different prognostic factors, a multivariate Cox
      proportional regression analysis was performed. The authors measured MMP
      activities in 33 surgically removed ovarian tumours, serum and ascites by
      applying zymographic technique. Fibronectin content was determined by Western
      blot analysis and quantitated by densitometry. RESULTS: The 5-year survival was
      90.0% and 30.9% in the case of ovarian tumours with low malignant potential and
      of epithelial ovarian cancers, respectively. Multivariate analysis identified
      adverse prognostic factors including advanced age (>60 years) and stage, high
      grade and suboptimal operation with residual macroscopic disease and the presence
      of ascites. However, the histological type was not identified to be an adverse
      prognostic factor in this study. No correlation could be seen between the
      histology of the ovarian tumours and the elevation of MMP-2/9 activity. More
      interestingly, however, MMP-9 expression and fibronectin concentration were
      significantly elevated and the activated forms of both MMP-9 and MMP-2 were more
      frequent in ovarian cancer patients who developed recurrent disease. CONCLUSION:
      A great deal of effort should be devoted to identification of further prognostic
      factors to improve treatment of ovarian cancer. These prognostic factors might
      help to identify those ovarian cancer patients at the time of diagnosis whose
      disease will have unfavourable outcome. Our data support the notion that high
      expression of MMP-9 and fibronectin indicates poor prognosis of ovarian cancer
      patients.

PMID- 15520878
TI  - The Tyr (albino) locus of the laboratory mouse.
AB  - The albino mouse was already known in ancient times and was apparently
      selectively bred in Egypt, China, and Japan. Thus, it is not surprising that the
      c or albino locus (now the Tyr locus) was among the first used to demonstrate
      Mendelian inheritance in mammals at the dawn of the past century. This locus is
      now known to encode tyrosinase, the rate-limiting enzyme in the production of
      melanin pigment, and the molecular basis of the albino ( Tyr(c)) mutation is
      known. Here we describe the congenic series of Tyr-locus alleles, from wild type
      to null ( albino). We compare eye and skin pigmentation phenotypes and the
      genetic lesions that cause each. We suggest that this panel of congenic mutants
      contains rich, untapped resources for the study of many questions of basic cell
      biological interest.

PMID- 15520879
TI  - Klotho gene variation and expression in 20 inbred mouse strains.
AB  - A defect in klotho gene expression in the mouse results in a syndrome that
      resembles human aging, with greatly shortened lifespan, arteriosclerosis, and
      defective hearing. In an effort to find functional murine variants of klotho, we
      sequenced the gene and examined renal expression of the secreted and membrane
      bound Klotho isoforms from 16 laboratory-derived and 4 wild-derived inbred
      strains. Among the laboratory-derived strains, no sequence variation was found in
      any of the exons or intron-exon boundaries. Among the wild-derived strains, we
      found 45 sequence variants with six resulting in amino acid substitutions. One
      wild-derived strain, SPRET/Ei, had four amino acid substitutions and higher
      levels of the membrane form and total klotho mRNA. In addition, the membrane to
      secreted klotho expression ratio was elevated in three wild-derived strains with
      amino acid substitutions. Interestingly, SPRET/Ei mice have longer lifespans,
      decreased atherosclerosis risk factors, and better hearing than almost all other
      mouse strains.

PMID- 15520880
TI  - Mouse functional genomics requires standardization of mouse handling and housing
      conditions.
AB  - The study of mouse models is crucial for the functional annotation of the human
      genome. The recent improvements in mouse genetics now moved the bottleneck in
      mouse functional genomics from the generation of mutant mice lines to the
      phenotypic analysis of these mice lines. Simple, validated, and reproducible
      phenotyping tests are a prerequisite to improving this phenotyping bottleneck. We
      analyzed here the impact of simple variations in animal handling and housing
      procedures, such as cage density, diet, gender, length of fasting, as well as
      site (retro-orbital vs. tail), timing, and anesthesia used during venipuncture,
      on biochemical, hematological, and metabolic/endocrine parameters in adult
      C57BL/6J mice. Our results, which show that minor changes in procedures can
      profoundly affect biological variables, underscore the importance of establishing
      uniform and validated animal procedures to improve reproducibility of mouse
      phenotypic data.

PMID- 15520881
TI  - Quantitative trait loci for steady-state platelet count in mice.
AB  - Platelet count in humans is a strongly genetically regulated trait, with
      approximately 85% of the interindividual variance in platelet numbers
      attributable to genetic factors. Inbred mouse strains also have strain-specific
      platelet count ranges. As part of a project to identify novel factors that
      regulate platelet count, we identified two inbred mouse strains, CBA/CaH and
      QSi5, with substantial differences in platelet count (mean values of 581 vs. 1062
      x 10(9)/L). An F(2) intercross resource of 1126 animals was bred from these two
      parental strains for a genomewide scan for quantitative trait loci (QTL) for
      platelet count. QTL were identified on MMU1 (LOD 6.8, p < 0.0005) and MMU11 (LOD
      11.2, p < 0.0005) by selectively genotyping animals from the extremes of the F(2)
      platelet count distribution. Three other QTL of suggestive statistical
      significance were also detected on MMU7, 13, and 17. It is noteworthy that no QTL
      were detected in the vicinity of the genes encoding thrombopoietin ( Thpo), and
      its receptor ( c-Mpl), both known to influence platelet production. Comparison of
      gene expression levels between the parental mouse strains by microarrays also
      showed little difference in the mRNA levels of these known candidate genes. These
      results represent the first published use of a genetic linkage-based approach in
      a mouse model toward the identification of genetic factors that regulate platelet
      count.

PMID- 15520882
TI  - Characterization of the dog Agouti gene and a nonagoutimutation in German
      Shepherd Dogs.
AB  - The interaction between two genes, Agouti and Melanocortin-1 receptor ( Mc1r),
      produces diverse pigment patterns in mammals by regulating the type, amount, and
      distribution pattern of the two pigment types found in mammalian hair: eumelanin
      (brown/black) and pheomelanin (yellow/red). In domestic dogs ( Canis familiaris),
      there is a tremendous variation in coat color patterns between and within breeds;
      however, previous studies suggest that the molecular genetics of pigment-type
      switching in dogs may differ from that of other mammals. Here we report the
      identification and characterization of the Agouti gene from domestic dogs,
      predicted to encode a 131-amino-acid secreted protein 98% identical to the fox
      homolog, and which maps to chromosome CFA24 in a region of conserved linkage.
      Comparative analysis of the Doberman Pinscher Agouti cDNA, the fox cDNA, and 180
      kb of Doberman Pinscher genomic DNA suggests that, as with laboratory mice,
      different pigment-type-switching patterns in the canine family are controlled by
      alternative usage of different promoters and untranslated first exons. A small
      survey of Labrador Retrievers, Greyhounds, Australian Shepherds, and German
      Shepherd Dogs did not uncover any polymorphisms, but we identified a single
      nucleotide variant in black German Shepherd Dogs predicted to cause an Arg-to-Cys
      substitution at codon 96, which is likely to account for recessive inheritance of
      a uniform black coat.

PMID- 15520883
TI  - Comparative map between the domestic pig and dog.
AB  - Cross-species chromosome painting with probes derived from flow-sorted dog and
      human chromosomes was used to construct a high-resolution comparative map for the
      pig. In total 98 conserved autosomal segments between pig and dog were detected
      by probes specific for the 38 autosomes and X Chromosome of the dog. Further
      integration of our results with the published human--dog and cat--dog comparative
      maps, and with data from comparative gene mapping, increases the resolution of
      the current pig--human comparative map. It allows for the conserved syntenies
      detected in the pig, human, and cat to be aligned against the putative ancestral
      karyotype of eutherian mammals and for the history of karyotype evolution of the
      pig lineage to be reconstructed. Fifteen fusions, 17 fissions, and 23 inversions
      are required to convert the ancestral mammalian karyotype into the extant
      karyotype of the pig.

PMID- 15520884
TI  - An interactive bovine in silico SNP database (IBISS).
AB  - An interactive bovine in silico SNP (IBISS) database has been created through the
      clustering and aligning of bovine EST and mRNA sequences. Approximately 324,000
      EST and mRNA sequences were clustered to produce 29,965 clusters (producing
      48,679 consensus sequences) and 48,565 singletons. A SNP screening regime was
      placed on variations detected in the multiple sequence alignment files to
      determine which SNPs are more likely to be real rather than sequencing errors. A
      small subset of predicted SNPs was validated on a diverse set of bovine DNA
      samples using PCR amplification and sequencing. Fifty percent of the predicted
      SNPs in the "putative >1" category were polymorphic in the population sampled.
      The IBISS database represents more than just a SNP database; it is also a genomic
      database containing uniformly annotated predicted gene mRNA and protein
      sequences, gene structure, and genomic organization information.

PMID- 15520885
TI  - Comparative PRNP genotyping of U.S. cattle sires for potential association with
      BSE.
AB  - The recent discovery of significant associations between bovine spongiform
      encephalopathy (BSE) susceptibility in German cattle and the frequency
      distributions of insertion/deletion (indel) polymorphisms within the bovine PRNP
      gene prompted an evaluation of 132 commercial U.S. artificial insemination (AI)
      sires from 39 breeds. Forward primer sequences from published primer sets
      targeting indels within the putative bovine PRNP promoter, intron 1, and the 3'
      UTR (untranslated region) were synthesized with unique 5' fluorescent labels and
      utilized to develop a rapid multiplexed PCR assay for identifying BSE-associated
      indels as well as facilitating polymorphism analyses and/or marker-assisted
      selection. Significant differences ( p < 0.05 all tests) were detected between
      the frequencies of bovine PRNP promoter alleles for 48 healthy German cattle
      previously described and 132 commercial U.S. cattle sires. The frequency of the
      23-bp promoter allele observed for commercial U.S. cattle sires strongly
      resembled that recently described for 43 BSE-affected German cattle. No
      significant difference ( p = 0.051) was detected between the distributions of
      promoter genotypes for healthy German cattle and our panel of commercial U.S.
      cattle sires. Interestingly, significant differences ( p < 0.01; p < 0.02) were
      also noted between the frequencies and distributions of intron 1 alleles and
      genotypes, respectively, for BSE-affected German cattle and our panel of U.S.
      cattle sires. No significant allelic or genotypic differences were detected for
      the 14-bp 3' UTR indel for any given comparison between German cattle and
      commercial U.S. cattle sires.

PMID- 15520886
TI  - Bovine beta-defensins: identification and characterization of novel bovine beta
      defensin genes and their expression in mammary gland tissue.
AB  - beta-Defensin genes code for multifunctional peptides with a broad-range
      antimicrobial activity. In this project we hypothesized that beta-defensin genes
      may be candidate genes for resistance to mastitis. In this article we describe
      the identification and genomic characterization of eight bovine beta-defensin
      genes, including six novel defensin genes and two pseudogenes. Expression in the
      bovine mammary gland of one of the novel genes, DEFB401, has been demonstrated,
      as well as the expression of LAP, TAP, DEFB1, BNBD3, BNBD9, and BNBD12. For
      genomic characterization, 20 BACs from two different bovine BAC libraries (RZPD
      numbers 750 and 754) were isolated by PCR screening with beta-defensin consensus
      primers derived from published sequences. PCR products from BACs generated with
      consensus primers have been subcloned and sequenced, revealing a total of 16
      genes and two pseudogenes. Six novel beta-defensin genes share the typical exon
      intron structure and are highly homologous to published bovine beta-defensin
      genes. They are named DEFB401- DEFB405 and LAP-like, and two novel pseudogenes
      are named EBD-P and EBD-P2. Analysis of mammary gland tissue-derived cDNA from
      nine cows with different clinical findings demonstrated the expression of several
      beta-defensin genes mentioned above. First results indicate that the lactational
      status of the cow presumably has no influence on gene expression. Competent
      knowledge of antimicrobial activity of beta-defensins from literature, the
      abundance of beta-defensin mRNA in the bovine mammary gland, and the inducibility
      of some genes give first evidence that beta-defensins may play a role in local
      host defense during udder infections.

PMID- 15520887
TI  - Polymorphisms in equine immune response genes and their associations with
      infections.
AB  - Polymorphic markers identified in the horse genes encoding the interleukin 12 p40
      subunit, interferon gamma, tumor necrosis factor receptor 1, and inducible nitric
      oxide synthase were identified and tested, along with additional markers, for
      associations with two important horse infections: Rhodococcus equi and Lawsonia
      intracellularis. Eight immune response-related and 14 microsatellite loci
      covering 12 out of 31 equine autosomes were used for the association analysis.
      Markers located on horse Chromosomes Eca10 and 15 were significantly associated
      with the presence of high numbers of R. equi in transtracheal aspirates.
      Significant associations of markers located on Eca9, 15, and 21 with fecal
      shedding of Lawsonia intracellularis were found. Marginal associations with tumor
      necrosis factor alpha, interferon gamma, and other genes suggested that
      variations in immune response-related genes could underlie the phenotypic
      variation observed.

PMID- 15520888
TI  - Analysis of a marsupial MHC region containing two recently duplicated class I
      loci.
AB  - A 37-kb cosmid containing two complete major histocompatibility complex (MHC)
      class I alpha chain loci from the opossum Monodelphis domestica was isolated,
      fully sequenced, and characterized. This sequence represents the largest
      contiguous genomic sequence reported for the MHC region of a nonplacental mammal.
      Based on particular conserved amino acid residues, and limited expression
      analyses, the two MHC-I loci, designated ModoUB and ModoUC, appear to encode
      functional MHC-I molecules. The two coding regions are 98% identical at the
      nucleotide level; however, their promoter regions differ significantly. Two CpG
      islands present in the cosmid sequence correspond to the two coding regions.
      Twelve microsatellites and six retroelements were also present in the cosmid. The
      retroelements share highest sequence homology to the CORE-SINE family of
      retroelements. Due to high sequence identity, it is very likely that ModoUB and
      ModoUC loci are products of recent gene duplication that occurred less than 4
      million years ago.

PMID- 15520889
TI  - A framework for net environmental benefit analysis for remediation or restoration
      of contaminated sites.
AB  - Net environmental benefits are gains in value of environmental services or other
      ecological properties attained by remediation or ecological restoration minus the
      value of adverse environmental effects caused by those actions. Net environmental
      benefit analysis (NEBA) is a methodology for comparing and ranking net
      environmental benefits associated with multiple management alternatives. A NEBA
      for chemically contaminated sites typically involves comparison of several
      management alternatives: (1) leaving contamination in place; (2) physically,
      chemically, or biologically remediating the site through traditional means; (3)
      improving ecological value through onsite and offsite restoration alternatives
      that do not directly focus on removal of chemical contamination; or (4) a
      combination of those alternatives. NEBA involves activities that are common to
      remedial alternatives analysis for state regulations and the Comprehensive
      Environmental Response, Compensation, and Liability Act, post-closure and
      corrective action permits under the Resource Conservation and Recovery Act,
      evaluation of generic types of response actions pertinent to the Oil Pollution
      Act, and land management actions that are negotiated with regulatory agencies in
      flexible regulatory environments (i.e., valuing environmental services or other
      ecological properties, assessing adverse impacts, and evaluating remediation or
      restoration options). This article presents a high-level framework for NEBA at
      contaminated sites with subframeworks for natural attenuation (the contaminated
      reference state), remediation, and ecological restoration alternatives. Primary
      information gaps related to NEBA include nonmonetary valuation methods, exposure
      response models for all stressors, the temporal dynamics of ecological recovery,
      and optimal strategies for ecological restoration.

PMID- 15520890
TI  - Integrating economic development and the environment: artisan fishing production
      in Guanabara Bay, Rio de Janeiro.
AB  - The adoption of environmentally sustainable techniques by cooperatives and small
      companies results in specific difficulties rarely discussed in the literature.
      This paper describes an "action-research" carried out by seafood cultivators and
      university researchers in Guanabara Bay, which resulted in the substitution of
      the previous technique, based on extraction, by one without negative
      environmental impacts. The economic results have been satisfactory, so it can be
      expected that this activity may become more widespread in the region.

PMID- 15520891
TI  - Variability of lotic macroinvertebrate assemblages and stream habitat
      characteristics across hierarchical landscape classifications.
AB  - Streams are naturally hierarchical systems, and their biota are affected by
      factors effective at regional to local scales. However, there have been only a
      few attempts to quantify variation in ecological attributes across multiple
      spatial scales. We examined the variation in several macroinvertebrate metrics
      and environmental variables at three hierarchical scales (ecoregions, drainage
      systems, streams) in boreal headwater streams. In nested analyses of variance,
      significant spatial variability was observed for most of the macroinvertebrate
      metrics and environmental variables examined. For most metrics, ecoregions
      explained more variation than did drainage systems. There was, however, much
      variation attributable to residuals, suggesting high among-stream variation in
      macroinvertebrate assemblage characteristics. Nonmetric multidimensional scaling
      (NMDS) and multiresponse permutation procedure (MRPP) showed that assemblage
      composition differed significantly among both drainage systems and ecoregions.
      The associated R-statistics were, however, very low, indicating wide variation
      among sites within the defined landscape classifications. Regional delineations
      explained most of the variation in stream water chemistry, ecoregions being
      clearly more influential than drainage systems. For physical habitat
      characteristics, by contrast, the among-stream component was the major source of
      variation. Distinct differences attributable to stream size were observed for
      several metrics, especially total number of taxa and abundance of algae-scraping
      invertebrates. Although ecoregions clearly account for a considerable amount of
      variation in macroinvertebrate assemblage characteristics, we suggest that a
      three-tiered classification system (stratification through ecoregion and habitat
      type, followed by assemblage prediction within these ecologically meaningful
      units) will be needed for effective bioassessment of boreal running waters.

PMID- 15520892
TI  - Recent evolution of natural hazard management policy in France, the example of
      Serre-Chevalier (French Alps).
AB  - Since the 1960s, the development of the Serre-Chevalier winter and summer resort
      has led to a rapid extension of the urban fabric on the territory of the village
      of St-Chaffrey. On July 9, 1981, the new neighborhoods built on the alluvial fan
      of the Verdarel torrent were partly devastated by a channeled debris flow. This
      disaster prompted the civil authorities to set up an extensive fluvial regulation
      system, which rapidly contributed to recreating a climate of confidence and
      security favorable to continuing urban expansion. The combination of catastrophic
      floods in July 1995, and a new security-oriented national policy on natural
      hazards, nevertheless led to a return to precautionary measures. The St-Chaffrey
      town council has therefore been forced by the State to accept a building-free
      zone on the land-use plan. This measure is perceived as a real denial of the
      local efficacy of the flood and landslide risk management policy as carried out
      by the council of St-Chaffrey during the previous 20 years.

PMID- 15520893
TI  - The effectiveness of plant conservation: a case study of Opole Province,
      southwest Poland.
AB  - This work presents a method of assessing plant conservation effectiveness in a
      given region, which takes into account the legal, species-centered protection,
      ecosystem conservation, ex situ conservation, restorations and translocations,
      reintroductions, and monitoring. In order to illustrate the conservation
      effectiveness, both legally protected species of plants and threatened species
      were examined. The conservation effectiveness of legally protected species was
      estimated to have a low value of 23.328 points (pts) according to the methods of
      calculation. Habitat conservation is insufficient for these species. Almost 40%
      of all localities are deprived of any ecosystem protection. The conservation
      effectiveness of the threatened group of species scored a very low value of 13.46
      pts. The major reason for this result is a very low level of species protection.
      Less than 30% of the threatened taxa are under legal preservation and some
      species from the Orobanche and Cuscuta genera are treated as harmful organisms,
      which it is obligatory to control within the province territory. Almost 30% of
      all localities of threatened species are deprived of any ecosystem protection and
      only 10% lie inside nature reserves. It is suggested that the conclusion of this
      investigation be used in the preparation and realization of the regional
      floristic diversity preservation strategy.

PMID- 15520894
TI  - An application and evaluation of the CAL3QHC model for predicting carbon monoxide
      concentrations from motor vehicles near a roadway intersection in Muscat, Oman.
AB  - The CAL3QHC model was used to predict carbon monoxide (CO) concentrations from
      motor vehicles at an existing urban intersection (Star Cinema in Muscat area,
      Oman). The CO concentrations predicted from the model were compared with those
      measured in the field. Predicted average CO concentrations were found to compare
      favorably with measured values obtained at all eight receptors considered within
      the modeled intersection. In general, the comparison indicates good agreement
      with some underprediction for CO. For receptor 6, the model overpredicts the
      average CO concentration. This overprediction is associated with the presence of
      trees and green area in the location of receptor 6. In general, the measurements
      and the model results indicated that the highest CO concentrations were found to
      occur close to the intersection and, hence, a decrease in the concentration
      levels was seen as the distance from the road increased. The results indicated
      that the levels of CO were well below the ambient air quality standard and that
      probably no health risk was present in areas adjacent to the star cinema
      intersection. However, the predicted worst-case 1-h CO concentrations assuming
      inversion atmospheric stability conditions (class F) and wind speed of 1 m/s
      indicated that the levels of CO were close to or higher than the Oman's National
      Ambient Air Quality Standards (NAAQS) value of 35 ppm at all receptors
      considered. The results of this study are useful in transport development and
      traffic management planning.

PMID- 15520895
TI  - Destruction of wetlands and waterbird populations by dams and irrigation on the
      Murrumbidgee River in arid Australia.
AB  - The Lowbidgee floodplain is the Murrumbidgee River's major wetland in
      southeastern Australia. From more than 300,000 ha in the early 1900s, at least
      76.5% was destroyed (58%) or degraded (18%) by dams (26 major storages),
      subsequent diversions and floodplain development. Diversions of about 2,144,000
      ML year(-1) from the Murrumbidgee River come from a natural median flow of about
      3,380,000 ML year(-1) providing water for Australia's capital, hydroelectricity,
      and 273,000 ha of irrigation. Diversions have reduced the amount of water
      reaching the Lowbidgee floodplain by at least 60%, from 1888 to 1998. About
      97,000 ha of Lowbidgee wetland was destroyed by development of the floodplain for
      an irrigation area (1975-1998), including building of 394 km of channels and
      2,145 km of levee banks. Over 19 years (1983-2001), waterbird numbers estimated
      during annual aerial surveys collapsed by 90%, from an average of 139,939 (1983
      1986) to 14,170 (1998-2001). Similar declines occurred across all functional
      groups: piscivores (82%), herbivores (87%), ducks and small grebe species (90%),
      large wading birds (91%), and small wading birds (95%), indicating a similar
      decline in the aquatic biota that formed their food base. Numbers of species also
      declined significantly by 21%. The Lowbidgee floodplain is an example of the
      ecological consequences of water resource development. Yanga Nature Reserve,
      within the Lowbidgee floodplain, conserved for its floodplain vegetation
      communities, will lose these communities because of insufficient water. Until
      conservation policies adequately protect river flows to important wetland areas,
      examples such as the Lowbidgee will continue to occur around the world.

PMID- 15520896
TI  - Stricter ozone ambient air quality standard has beneficial effect on ponderosa
      pine in California.
AB  - Ambient air quality standards and control strategies are implemented to protect
      humans and vegetation from adverse effects. We used a process-based tree-growth
      model (TREGRO) to show that over the past 37 years, changes in O(3) exposure,
      with accompanying variation in climate, are reflected in changes in the growth of
      Pinus ponderosa Dougl. ex Laws. in the San Bernardino Mountains near Los Angeles,
      California, USA. Despite variation in temperature and precipitation over the
      study period (1963-1999), O(3) exposure consistently reduced simulated tree
      growth. Simulated growth reductions increased concurrent with increasing O(3)
      exposure. The maximum growth reduction occurred in 1979. As O(3) exposures
      decreased during the 1980s and 1990s, effects on growth also decreased. This
      implies that emission control strategies taken to reduce exposures to attain O(3)
      standards benefited P. ponderosa growth in the San Bernardino Mountains. This
      modeling approach provides a powerful tool for solving the difficult problem of
      evaluating regulatory effectiveness by simulating plant response using long-term
      climate and air pollution exposure records for a given region.

PMID- 15520897
TI  - An innovative index for evaluating water quality in streams.
AB  - A water quality index expressed as a single number is developed to describe
      overall water quality conditions using multiple water quality variables. The
      index consists of water quality variables: dissolved oxygen, specific
      conductivity, turbidity, total phosphorus, and fecal coliform. The objectives of
      this study were to describe the preexisting indices and to define a new water
      quality index that has advantages over these indices. The new index was applied
      to the Big Lost River Watershed in Idaho, and the results gave a quantitative
      picture for the water quality situation. If the new water quality index for the
      impaired water is less than a certain number, remediation-likely in the form of
      total maximum daily loads or changing the management practices-may be needed. The
      index can be used to assess water quality for general beneficial uses.
      Nevertheless, the index cannot be used in making regulatory decisions, indicate
      water quality for specific beneficial uses, or indicate contamination from trace
      metals, organic contaminants, and toxic substances.

PMID- 15520898
TI  - Application of the index of biotic integrity methodology to New Zealand
      freshwater fish communities.
AB  - An index of biotic integrity (IBI) was developed for freshwater fish in New
      Zealand streams. Data on freshwater fish occurrence for 5497 sites over the
      entire country were obtained from the New Zealand freshwater fish database for
      the period 1980-2002. Environmental habitat descriptors for the stream watersheds
      above or at each of these sites were obtained from an existing river environment
      classification using a geographic information system. Of the many IBI metrics in
      use globally, only six were adapted and applied because of differences between
      the fish fauna of New Zealand and the United States. A number of evaluation
      methods showed that all six metrics contributed to the overall IBI scores with
      high levels of consistency. The IBI assessment of sites sampled at different
      times showed high levels of temporal concordance. The IBI scores differed
      significantly among the geological areas, the sampling method used, and the year
      of survey. Overall, the results presented demonstrate the potential for New
      Zealand freshwater fish to be used to assess river condition at large spatial
      scales in New Zealand in the absence of specifically selected reference sites.
      This application demonstrates the effectiveness of the IBI approach even with a
      fauna of limited diversity and limited ecological specialisation as in the New
      Zealand fish fauna.

PMID- 15520899
TI  - Mapping land-cover and mangrove structures with remote sensing techniques: a
      contribution to a synoptic GIS in support of coastal management in North Brazil.
AB  - This article deals with the development and application of a cartographic
      database for a synoptic Geographic Information System (GIS). Its purpose is the
      storage and evaluation of the heterogeneous datasets of the interdisciplinary
      scientific research program MADAM (Mangrove Dynamics and Management), which aims
      to develop recommendations for a tailored integrated coastal management scheme
      for the mangrove ecosystem at Braganca (North Brazil). The article describes the
      integration of remote sensing data, aerial photographs, as well as point data
      provided by fieldwork from different scientific fields. Using various innovative
      processing techniques and different scale-resolution levels, an assessment of
      temporal-spatial changes of the mangrove peninsula and the adjacent rural
      socioeconomic impact area, the type of mangrove structure, as well as a land-use
      cover analyses was undertaken. The definition of the spatial level of detail was
      found to be a major issue in the development of the GIS, as well as during the
      processing and analysis procedures. A division between strong and weak patterns
      in the mangrove ecosystem could be made, which implies different management
      measures and sets of specific interdisciplinary studies and monitoring at
      hierarchical scales.

PMID- 15520900
TI  - Long-term monitoring and prediction for settlement and composition of refuse in
      Shanghai Laogang Municipal Landfill.
AB  - Parameters about composition of refuse such as mass percentage of biodegradable
      matter, volatile solid, organic carbon, cellulose, total sugar, and settlement
      were monitored and analyzed in a large-scale experimental unit. The empirical
      formulas between composition and refuse age were established in terms of the data
      obtained from the experimental unit and verified by comparing with the
      corresponding parameters of refuse in the closed landfill units from 1991 until
      1994 in the Shanghai Laogang Municipal Landfill. Furthermore, the long-term
      prediction for the composition of refuse was made, and it was predicted that the
      half-life is 7 to 11 years for biodegradable matter, 9 to 12 years for organic
      carbon or volatile solid, 7 to 16 years for cellulose, and 4 to 6 years for total
      sugar. In addition, a mathematical model, based on the mechanism of refuse
      biodegradation in the landfill, was developed to simulate the relationship
      between the settlement and the refuse age and manifests the secondary settlement
      potential. The mathematical model was proved not only to be reliable but also
      should be accurate for predicting the settlement of the landfill. The secondary
      settlement, which mainly results from the slow and gradual biodegradation of
      refuse, is linear with respect to the exponent of refuse age. Finally, according
      to the settlement model and empirical biodegradation formulas, it may be
      predicted that, 79.4% of biodegradable matter, 92.9% of total sugar, 72.7% of
      volatile solid and organic carbon, and 73.1% of cellulose will be biodegraded and
      that 79% of the maximum secondary settlement potential will occur before the
      Shanghai Laogang Municipal Landfill is in a high stabilization situation, i.e.,
      approximately 21 years after final closure.

PMID- 15520901
TI  - Abdominal and pelvic CT in the HIV-positive population.

PMID- 15520904
TI  - Regulation of insulin secretion in islets of Langerhans by Ca(2+)channels.
AB  - Insulin secretion from beta-cells of the pancreatic islets of Langerhans is
      triggered by Ca(2+) influx through voltage-dependent Ca(2+) channels.
      Electrophysiological and molecular studies indicate that beta-cells express
      several subtypes of these channels. This review discusses their roles in
      regulating insulin secretion, focusing on recent studies using beta-cells,
      exogenous expression systems, and Ca(2+) channel knockout mice. These
      investigations reveal that L-type Ca(2+) channels in the beta-cell physically
      interact with the secretory apparatus by binding to synaptic proteins on the
      plasma membrane and insulin granule. As a result, Ca(2+) influx through L-type
      channels efficiently and rapidly stimulates release of a pool of insulin granules
      in close contact with the channels. Thus, L-type Ca(2+) channel activity is
      preferentially coupled to exocytosis in the beta-cell, and plays a critical role
      in regulating the dynamics of insulin secretion. Non-L-type channels carry a
      significant portion of the total voltage-dependent Ca(2+) current in beta-cells
      and cell lines from some species, but nevertheless account for only a small
      fraction of insulin secretion. These channels may regulate exocytosis indirectly
      by affecting membrane potential or second messenger signaling pathways. Finally,
      voltage-independent Ca(2+) entry pathways and their potential roles in beta-cell
      function are discussed. The emerging picture is that Ca(2+) channels regulate
      insulin secretion at multiple sites in the stimulus-secretion coupling pathway,
      with the specific role of each channel determined by its biophysical and
      structural properties.

PMID- 15520905
TI  - Intracellular delivery of carbohydrates into mammalian cells through swelling
      activated pathways.
AB  - Volume changes of human T-lymphocytes (Jurkat line) exposed to hypotonic
      carbohydrate-substituted solutions of different composition and osmolality were
      studied by videomicroscopy. In 200 mOsm media the cells first swelled within 1-2
      min and then underwent regulatory volume decrease (RVD) to their original
      isotonic volume within 10-15 min. RVD also occurred in strongly hypotonic 100
      mOsm solutions of di- and trisaccharides (trehalose, sucrose, raffinose). In
      contrast to oligosaccharide media, 100 mOsm solutions of monomeric carbohydrates
      (glucose, galactose, inositol and sorbitol) inhibited RVD. The complex volumetric
      data were analyzed with a membrane transport model that allowed the estimation of
      the hydraulic conductivity and volume-dependent solute permeabilities. We found
      that under slightly hypotonic stress (200 mOsm) the cell membrane was impermeable
      to all carbohydrates studied here. Upon osmolality decrease to 100 mOsm, the
      membrane permeability to monomeric carbohydrates increased dramatically
      (apparently due to channel activation caused by extensive cell swelling), whereas
      oligosaccharide permeability remained very poor. The size-selectivity of the
      swelling-activated sugar permeation was confirmed by direct chromatographic
      measurements of intracellular sugars. The results of this study are of interest
      for biotechnology, where sugars and related compounds are increasingly being used
      as potential cryo- and lyoprotective agents for preservation of rare and valuable
      mammalian cells and tissues.

PMID- 15520906
TI  - Protein- and lipid-reactive agents alter outer hair cell lateral membrane motor
      charge movement.
AB  - Outer hair cells from the mamma*lian cochlea are mechanically active cells that
      rely on charged voltage sensors within their lateral plasma membrane to gate the
      integral membrane motor protein, prestin, into one of two area states. Here we
      use protein and lipid reactive reagents to probe the influence of these bilayer
      components on motor-induced nonlinear membrane capacitance. Of the protein
      reactive reagents tested, cross-linking and sulfhydryl reagents were most
      effective in altering steady state and time-varying motor activity. Of the lipid
      altering agents, chloroform and HePC were most effective. Chloroform, in
      particular, drastically modified the susceptibility of the motor to prior voltage
      (initial conditions). Our data suggest that outer hair cell motor activity
      derives substantially from interactions with its lipid environment.

PMID- 15520907
TI  - Distinct Ca(2+)-permeable cation currents are activated by internal Ca(2+)-store
      depletion in RBL-2H3 cells and human salivary gland cells, HSG and HSY.
AB  - Store-operated Ca(2+) influx, suggested to be mediated via store-operated cation
      channel (SOC), is present in all cells. The molecular basis of SOC, and possible
      heterogeneity of these channels, are still a matter of controversy. Here we have
      compared the properties of SOC currents ( I(SOC)) in human submandibular glands
      cells (HSG) and human parotid gland cells (HSY) with I(CRAC) (Ca(2+) release
      activated Ca(2+) current) in RBL cells. Internal Ca(2+) store-depletion with
      IP(3) or thapsigargin activated cation channels in all three cell types. 1 muM
      Gd(3+) blocked channel activity in all cells. Washout of Gd(3+) induced partial
      recovery in HSY and HSG but not RBL cells. 2-APB reversibly inhibited the
      channels in all cells. I(CRAC )in RBL cells displayed strong inward rectification
      with E(rev)(Ca) = >+90 mV and E(rev) (Na) = +60 mV. I(SOC) in HSG cells showed
      weaker rectification with E(rev)(Ca) = +25 mV and E(rev)(Na) = +10 mV. HSY cells
      displayed a linear current with E(rev) = +5 mV, which was similar in Ca(2+)- or
      Na(+)-containing medium. pCa/ pNa was >500, 40, and 4.6 while pCs / pNa was
      0.1,1, and 1.3, for RBL, HSG, and HSY cells, respectively. Evidence for anomalous
      mole fraction behavior of Ca(2+)/Na(+) permeation was obtained with RBL and HSG
      cells but not HSY cells. Additionally, channel inactivation with Ca(2+) + Na(+)
      or Na(+) in the bath was different in the three cell types. In aggregate, these
      data demonstrate that distinct store-dependent cation currents are stimulated in
      RBL, HSG, and HSY cells. Importantly, these data suggest a molecular
      heterogeneity, and possibly cell-specific differences in the function, of these
      channels.

PMID- 15520908
TI  - CO(2) sensitivity of voltage gating and gating polarity of gapjunction channels-
      connexin40 and its COOH-terminus-truncated mutant.
AB  - The CO(2) sensitivity of transjunctional voltage ( V(j)) gating was studied by
      dual voltage clamp in oocytes expressing mouse Cx40 or its COOH terminus (CT)
      truncated mutant (Cx40-TR). V(j) sensitivity, determined by a standard V(j)
      protocol (20 mV V(j) steps, 120 mV maximal), decreased significantly with
      exposure to 30% CO(2). The Boltzmann values of control versus CO(2)-treated
      oocytes were: V(0) = 36.3 and 48.7 mV, n = 5.4 and 3.7, and G(j min) = 0.21 and
      0.31, respectively. CO(2) also affected the kinetics of V(j)-dependent
      inactivation of junctional current ( I(j)); the time constants of two-term
      exponential I(j) decay, measured at V(j) = 60 mV, increased significantly with
      CO(2) application. Similar results were obtained with Cx40-TR, suggesting that CT
      does not play a role in this phenomenon. The sensitivity of Cx40 channels to 100%
      CO(2) was also unaffected by CT truncation. There is evidence that CO(2)
      decreases the V(j) sensitivity of Cx26, Cx50 and Cx37 as well, whereas it
      increases that of Cx45 and Cx32 channels. Since Cx40, Cx26, Cx50 and Cx37 gate at
      the positive side of V(j), whereas Cx45 and Cx32 gate at negative V(j), it is
      likely that V(j) behavior with respect to CO(2)-induced acidification varies
      depending on gating polarity, possibly involving the function of the postulated
      V(j) sensor (NH(2)-terminus).

PMID- 15520909
TI  - Gastrointestinal bleeding.

PMID- 15520910
TI  - Endoscopic ultrasonography--new developments and interesting trends.

PMID- 15520911
TI  - Colonoscopy.

PMID- 15520912
TI  - Outcome of patients with esophageal carcinoma and suspicious celiac lymph nodes
      as determined by endoscopic ultrasonography.
AB  - BACKGROUND AND STUDY AIMS: The management of patients with esophageal cancer with
      malignant celiac lymph nodes (CLNs) is controversial. In this study we evaluated
      the management and survival of patients with positive CLN findings on endoscopic
      ultrasonography (EUS) and compared the outcome in surgically treated patients
      with that of nonsurgically treated patients. PATIENTS AND METHODS: The EUS
      database of the Academic Medical Center was retrospectively searched for patients
      with esophageal carcinoma and EUS-positive CLN. Follow-up comprised the review of
      medical charts and contact with general practitioners. RESULTS: From 1993 through
      2000, 78 patients with esophageal carcinoma and suspicious CLN were eligible for
      inclusion in this study. The median survival of patients with CLN size < 2 cm was
      13.5 months vs. 7.0 months for patients with CLN size >2 cm ( P = 0.01). In a
      multivariate model, CLN size was the only predictive factor for poor patient
      survival. Of the 78 study patients, 13 underwent a surgical resection and 65
      received nonsurgical treatment. The surgical group was significantly younger and
      all patients in this group had CLN size < 2 cm. The median survival for the
      surgical group was 13.7 months vs. 13.5 months for the nonsurgical group with CLN
      size < 2 cm ( P = 0.63). CONCLUSIONS: In this retrospective study, CLN size was a
      significant predictor for poor survival. The surgically treated patients had a
      medium-term survival similar to that of nonsurgically treated patients with a CLN
      size < 2 cm. These findings underline the prognostic value of CLN size in
      patients with esophageal carcinoma.

PMID- 15520913
TI  - Influence of tumor characteristics on the accuracy of endoscopic ultrasonography
      in staging cancer of the esophagus and esophagogastric junction.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic ultrasonography (EUS) is the most accurate
      method of assessing the locoregional extent of cancer of the esophagus and
      esophagogastric junction. The aim of this study was to evaluate the influence of
      tumor-related factors such as length and location on the accuracy of EUS in
      staging these tumors. PATIENTS AND METHODS: Between January 1997 and September
      2002, 280 consecutive patients underwent preoperative EUS for staging cancer of
      the esophagus and esophagogastric junction. The influence of histopathology, the
      presence of Barrett's dysplasia or stenosis, and the location and length of the
      primary tumor on the accuracy of EUS for T, N, and M staging were studied.
      RESULTS: The overall accuracy rates of EUS for assessing the T, N, and M stages
      were 73 %, 80 %, and 78 %, respectively. The influence of the tumor's
      histopathology and the presence of Barrett's dysplasia or stenosis was minimal.
      The accuracy of EUS was greater in tumors 5 cm or less in size than in tumors
      larger than 5 cm (82 % vs. 52 % for the T stage, P < 0.05; 88 % vs. 59 % for the
      N stage, P < 0.05; and 92 % vs. 56 % for the M stage, P < 0.001). The low
      accuracy of T staging in larger tumors may be due to the exclusion of patients
      with local unresectability or distant metastases. EUS was also significantly
      better in esophageal tumors, particularly for identifying celiac trunk metastases
      (93 % vs. 63 %; P < 0.001). CONCLUSIONS: The accuracy of EUS for staging
      esophageal cancer is lower in tumors larger than 5 cm and in esophagogastric
      junction tumors than in tumors 5 cm in size or less and in esophageal tumors.
      These findings should be considered when treatment decisions are being taken.

PMID- 15520914
TI  - Pancreatic endosonography after Billroth II gastrectomy.
AB  - BACKGROUND AND STUDY AIMS: Prior Billroth II gastrectomy is considered a relative
      contraindication to endoscopic ultrasonography (EUS) of the pancreatic head. This
      study reviews experience with pancreatic EUS in such patients. PATIENTS AND
      METHODS: Eleven patients were identified who had previous Billroth II gastrectomy
      and underwent attempted pancreatic EUS. RESULTS: Examination of the pancreatic
      head was technically feasible in 10 of the patients. The inferior pancreatic
      head, ampulla, and periampullary ducts were seen in all; the superior pancreatic
      head and porta hepatis were visualized in 50 % of cases with radial echo
      endoscopes and 100 % with a linear-array echo endoscope. The pancreatic neck was
      fully imaged in 25 % of cases with radial echo endoscopes and in 60 % with a
      linear-array echo endoscope. One known pancreatic neck mass was not visualized.
      CONCLUSIONS: Pancreatic EUS is technically feasible in most patients with a prior
      Billroth II gastrectomy. Linear-array echo endoscopes provide a more complete
      examination than radial echo endoscopes. The pancreatic neck may be difficult to
      visualize.

PMID- 15520915
TI  - Measuring tumor volume with three-dimensional endoscopic ultrasonography: an
      experimental and clinical study (including video).
AB  - BACKGROUND AND STUDY AIMS: The Olympus EU-IP2 three-dimensional endoscopic
      ultrasound (3D-EUS) imaging system makes it possible to display tumors in three
      dimensions and estimate their volume. MATERIALS AND METHODS: Experimental and
      clinical studies of the volume estimation function of the Olympus EU-IP2 system
      was carried out to evaluate its accuracy and assess the extent of tumor shrinkage
      caused by fixation, dehydration, and staining. Results. In the experimental
      studies, compared with the actual volume of a 1000-mm (3) gelatin column, the
      estimated volume was found to be equivalent to 114 +/- 1.8 % with the 3R probe
      and 143 +/- 0.8 % with the 2R probe (mean plus or minus standard deviation). The
      mean estimated volume of tumor models was 127 +/- 8.5 % with the 3R probe and 131
      +/- 6.8 % with the 2R probe. Greater distance from the probe was associated with
      a greater degree of error than the target object's size, angle, or the number of
      traces of its outline made. In the clinical studies, compared with the
      histologically determined tumor volume (100 %), the mean estimated tumor volume
      was 178 +/- 48.2 % in situ, 168 +/- 31.3 % in resected specimens, and 137 +/-
      31.5 % after fixation. Fixation, dehydration, and staining were thus associated
      with tumor shrinkage. CONCLUSIONS: The volume of gastrointestinal lesions can be
      estimated by 3D-EUS, although it is overestimated in comparison with actual
      values. 3D-EUS also allows direct comparisons to be made between the tumor volume
      before surgery and the volume of fixed pathological specimens, so that the rate
      of tumor shrinkage can be estimated.

PMID- 15520916
TI  - Frequency and costs of echo endoscope repairs: results of a survey of
      endosonographers.
AB  - BACKGROUND AND STUDY AIMS: The need for repair of endoscopic ultrasound (EUS)
      equipment appears to be frequent and expensive. To better quantify the costs
      associated with echo endoscope failure, a survey of endosonographers was carried
      out. METHODS: A survey questionnaire concerning echo endoscope damage and repair
      and consequences of echo endoscope downtime over a 12-month period was sent to
      members of the American Society of Gastrointestinal Endoscopy who had cited an
      interest in EUS. RESULTS: Responses were received from 56 of 138 institutions
      where EUS was carried out (41 %). A median of 325 EUS procedures had been carried
      out in the past year and a median of two endosonographers were employed who used
      an average of three echo endoscopes. Two-thirds of institutions trained fellows.
      A total of 225 repairs were reported for leaks (47 %), mechanical failures (33
      %), images or optics difficulties (26 %), or other problems (1 %). Mechanical
      radial-scanning echo endoscopes tended to break, on average, after 68 procedures,
      while curved linear-array echo endoscopes failed after an average of 107
      procedures. Echo endoscope failures led to rescheduling of procedures at three
      quarters of institutions. Institutions paid an average of $ 10 534 over 12 months
      for echo endoscope repairs. The average repair cost per procedure was $ 41. There
      was an inverse relationship between quantity of procedures and the per-procedure
      repair rate ( P < 0.05). CONCLUSIONS: Direct and indirect costs of echo endoscope
      repairs are significant. Instrument failures are multifactorial; however
      instrument complexity, instrument age, and institutional inexperience may
      contribute to repair costs.

PMID- 15520917
TI  - Accuracy of magnetic resonance cholangiopancreatography for locating
      hepatolithiasis and detecting accompanying biliary strictures.
AB  - BACKGROUND AND STUDY AIMS: Magnetic resonance cholangiopancreatography (MRCP) is
      rapidly replacing diagnostic endoscopic retrograde cholangiopancreatography
      (ERCP) in various pancreaticobiliary diseases. This study was designed to
      evaluate the accuracy of MRCP in detection of hepatolithiasis and accompanying
      biliary strictures. PATIENTS AND METHODS: A prospective study over 2 years was
      conducted in 66 patients with primary intrahepatic stones. All patients with
      hepatolithiasis underwent percutaneous transhepatic cholangioscopy (PTC) within 2
      weeks of the MRCP examination. The MRCP findings were compared with those of PTC
      as the reference standard for assessing the location of intrahepatic stones and
      the presence or absence of accompanying biliary strictures. RESULTS: The
      sensitivity, specificity, and accuracy of MRCP for detecting and locating
      intrahepatic stones were 97 %, 99 %, and 98 %, respectively. The sensitivity,
      specificity, and accuracy of MRCP for detecting and locating intrahepatic bile
      duct strictures were 93 %, 97 %, and 97 %, respectively. During PTC, six of the
      66 patients (9 %) were found on histology to have intraductal cholangiocarcinoma
      in stone-bearing ducts, which had not been suspected on MRCP. CONCLUSIONS: In
      this study, MRCP allowed intrahepatic stones and accompanying biliary strictures
      to be located accurately. MRCP may therefore be able to replace diagnostic ERCP
      in patients with primary intrahepatic stones. However, MRCP had a limited ability
      to reveal concurrent intraductal cholangiocarcinoma associated with
      hepatolithiasis.

PMID- 15520918
TI  - Duodenal versus jejunal biopsies in suspected celiac disease.
AB  - BACKGROUND AND STUDY AIMS: In the past, small-bowel biopsies for diagnosis of
      celiac disease were taken from the jejunum with a suction capsule, but nowadays
      most physicians take endoscopic biopsies from the distal duodenum. To validate
      that practice we compared the diagnostic yield of endoscopic duodenal biopsies
      with that of endoscopic jejunal biopsies. In addition, we describe a method of
      orienting biopsy specimens optimally. PATIENTS AND METHODS: Upper endoscopy was
      performed with a colonoscope. Four jejunal and four duodenal biopsies were taken
      and oriented immediately thereafter. The pathologist rated the orientation as
      poor, adequate, or good, and histopathological results were expressed according
      to the Marsh classification. Jejunal and duodenal biopsy results were compared.
      RESULTS: 146 patients were included. Jejunal biopsies were taken in 142 patients,
      and Marsh I-II lesions were found in 56 and Marsh III lesions in 15 patients. In
      three patients duodenal biopsies were normal while jejunal biopsies showed Marsh
      I-II lesions. No discrepancies were found in patients with Marsh III lesions.
      Orientation was good in all biopsies. CONCLUSION: Duodenal biopsies are
      sufficient to diagnose full-blown celiac disease (Marsh III), but Marsh I-II
      lesions may be missed in some cases.

PMID- 15520919
TI  - Effects of colonoscopy on intracranial pressure: observation in a large animal
      model.
AB  - BACKGROUND AND STUDY AIMS: Increased intra-abdominal pressure has been associated
      with increased intracranial pressure. Bowel insufflation during colonoscopy may
      increase the intra-abdominal pressure. It was hypothesized that colonoscopy may
      be associated with intracranial pressure elevation subsequent to an elevation in
      intra-abdominal pressure. MATERIALS AND METHODS: Colonoscopy was carried out in
      seven anesthetized pigs, and the colonoscope was advanced up to 60 cm from the
      anal verge. Insufflation was used to allow safe advancement of the colonoscope
      and to allow visualization of the colon, in the same way as in the procedure
      performed in humans. Intra-abdominal pressure was measured by determining the
      hydrostatic pressure in the urinary bladder. A subarachnoid screw was used to
      monitor intracranial pressure. The mean arterial blood pressure and intra
      abdominal venous pressure were directly monitored via the femoral vessel access;
      all parameters were recorded before and during colonoscopy. RESULTS: A
      statistically significant elevation in intracranial pressure was demonstrated
      during colonoscopy. The average increase in intracranial pressure was 3.1 mm Hg.
      The intra-abdominal pressure and intra-abdominal venous pressure were also
      significantly elevated during the procedure. CONCLUSIONS: Colonoscopy may
      increase intracranial pressure due to an increase in intra-abdominal pressure.
      This may have clinical implications when colonoscopy is conducted in patients
      with brain pathology associated with high intracranial pressure.

PMID- 15520920
TI  - Balloon dilation of ileocolonic strictures in Crohn's disease.

PMID- 15520921
TI  - On writing (5): fabrication, falsification and plagerism in medical research and
      publishing.

PMID- 15520923
TI  - Four-Step endoscopic esophageal mucosal resection (EEMR) tube method of resection
      for early esophageal cancer.

PMID- 15520924
TI  - Subcapsular hepatic hematoma after guide wire injury during endoscopic retrograde
      cholangiopancreatography: management and review.
AB  - Complications of endoscopic retrograde cholangiopancreatography (ERCP) that are
      associated with the guide wire are fortunately rare, but may be more common than
      is reported. We describe the case of a 43-year-old woman with obstructive
      jaundice from metastatic pancreatic cancer who underwent an elective ERCP for
      biliary stent placement. This was complicated by guide wire-associated injury
      that resulted in the development and eventual rupture of a subcapsular hepatic
      hematoma and which was successfully treated with nonsurgical management. If
      identified and treated rapidly, using a multidisciplinary approach (i. e., with
      medical, interventional radiology, and surgical input), such patients can be
      conservatively managed.

PMID- 15520925
TI  - Ileal mucosa-associated lymphoid tissue lymphoma showing several ulcer scars
      detected using double-balloon endoscopy.
AB  - A 72-year-old man was admitted to our hospital to undergo a novel small
      intestinal endoscopic procedure. He had had occasional episodes of hematochezia
      over a 2-year period, during which he had been hospitalized twice previously.
      However, numerous investigations, including hematological and biochemical
      studies, gastroscopy, colonoscopy, computed tomography, scintigraphy, and
      angiography had failed to detect the source of bleeding in the gastrointestinal
      tract. On this admission, double-balloon enteroscopy was performed and revealed
      several ulcer scars with localized dilation of the ileum. Histopathological
      examination of the biopsy specimens revealed no abnormal findings. Partial
      resection of the ileum was performed to prevent further gastrointestinal
      bleeding, and histopathological examination of the resected specimen revealed
      aggregation of atypical lymphocytes, predominantly in the muscularis propria
      layer. Immunohistochemical examination demonstrated that the tumor cells were
      positive for CD20 and BCL2, but negative for UCHL1. Based on these findings, the
      lesion was diagnosed as a marginal-zone B-cell lymphoma of mucosa-associated
      lymphoid tissue. Eighteen months after surgery, the patient was still in complete
      remission.

PMID- 15520926
TI  - European job profile for endoscopy nurses--August 2004.

PMID- 15520927
TI  - Cost-effective therapeutic strategy for the management of bleeding gastric fundal
      varices.

PMID- 15520930
TI  - Spontaneous fracture of a biliary self-expanding metal stent.

PMID- 15520929
TI  - Volvulus of gastric tube reconstruction after transhiatal esophagectomy: an
      endoscopic solution.

PMID- 15520931
TI  - Combined use of needle-knife and bite biopsy in the diagnosis of a gastric
      submucosal tumor.

PMID- 15520932
TI  - Capsule endoscopy: in difficult cases the capsule can be ingested through an
      overtube.

PMID- 15520933
TI  - Small-bowel polyps in Peutz-Jeghers syndrome: diagnosis by wireless capsule
      endoscopy.

PMID- 15520934
TI  - Hepatic perforation: a complication of proximal biliary stent migration.

PMID- 15520936
TI  - Minimum training for right upper quadrant ultrasonography.
AB  - The objective of this study was to assess if 10 right upper quadrant (RUQ)
      ultrasound (US) examinations could be used as a minimum standard for training.
      This was a retrospective review of patients with suspected gallbladder pathology
      who underwent resident-performed RUQ US before operative or department of
      radiology evaluation. Two hundred twenty-four patients were examined using
      resident-performed RUQ US followed by gold standard evaluations. One hundred
      seventy-eight patients were evaluated by 13 residents who met the "minimum
      training" standard of 10 prior examinations. The results of resident-performed
      RUQ US for gallstones and/or cholecystitis are shown subsequently. Previous
      suggestions that 10 examinations could be used as a minimum standard for training
      in focused abdominal sonography for trauma examinations cannot be used for RUQ
      US. The ACEP 2001 guidelines for 25 examinations are more consistent with the
      learning curve suggested by our data.

PMID- 15520935
TI  - Mapping of a major locus that determines telomere length in humans.
AB  - Telomere length is a crucial factor for both normal chromosomal function and
      senescence. Mean telomere length in humans shows considerable interindividual
      variation and strong genetic determination. To see if a locus (or loci) affecting
      telomere length in humans could be mapped, we performed a quantitative-trait
      linkage analysis of mean leukocyte telomere-restriction-fragment (TRF) lengths,
      measured by Southern blotting, in 383 adult subjects comprising 258 sib pairs.
      Heritability of mean (+/-SE) TRF was 81.9%+/-11.8%. There was significant linkage
      (LOD score 3.20) of mean TRF length to a locus on chromosome 12, which explained
      49% of the overall variability in mean TRF length. We present preliminary
      analysis of a strong candidate gene in the region, the DNA helicase DDX11. In
      conclusion, we report mapping of the first locus that determines mean telomere
      length in humans. Identification of the gene involved and elucidation of its
      mechanism of action could have important implications for our understanding of
      chromosomal assembly, telomere biology, and susceptibility to age-related
      diseases.

PMID- 15520937
TI  - Chronic pain in the ED.
AB  - There has been increasing awareness concerning the problem of acute pain in ED
      patients. There has, however, been little attention devoted to chronic pain in ED
      patients. Our purpose was to determine the extent and severity of chronic pain in
      adult ED patients. Adult noncritical patients were interviewed to determine if
      they had chronic pain. The Chronic Pain Grade scale was used to grade the
      severity of the pain. Four hundred seventy-six patients were enrolled. One
      hundred ninety-three (40.6%) had chronic pain. Sixty-five (13.7%) identified
      their chronic pain as the reason for the ED visit. The spine and abdomen were the
      most common sites of chronic pain. Those with chronic pain were more likely to be
      unemployed (relative risk [RR], 1.77; 95% confidence interval [CI], 1.34-2.34),
      disabled (RR, 3.24; 95% CI, 1.95-5.40), and have had four or more ED visits in
      the past year (RR, 2.47; 95% CI, 1.76-3.47). A total of 32.1% had class 3 pain
      (high disability, moderately limiting) and 58.0% had class 4 pain (high
      disability, severely limiting). Many noncritical ED patients have chronic pain.
      They are high users of ED services and most have not been seen in a pain clinic.
      Further studies are indicated to further delineate the demographics of this
      population and determine which patients would best be served in other healthcare
      settings. In an effort to improve care, ED physicians should be educated in
      diagnosing and treating chronic pain.

PMID- 15520938
TI  - Risk factors for 72-hour admission to the ED.
AB  - This study's purpose was to identify risk factors for return and admission within
      72 hours of discharge from the emergency department (ED). During a 2-year period,
      104,584 patients were seen and discharged in the ED, and 493 (0.47%) patients
      returned within 72 hours requiring admission. Risk factors compared were age,
      sex, race, insurance status, and initial diagnosis. Initial visits were also
      characterized by weekday, means of arrival, time of arrival and discharge, and
      time between visits. Older patients, especially over 65 years, and patients with
      insurance for the elderly (Medicare) were at higher risk. The highest risk
      initial diagnosis categories were mental disorder (1.2%), genitourinary system
      (0.93%), and symptom-based diagnoses (0.76%). Also, a high proportion of patients
      arrived by ambulance. Patients at increased risk of early admission can be
      identified and should be the first target for prospective prevention strategies
      that seek to minimize high-risk early returns to the ED.

PMID- 15520939
TI  - Comparison of sexual assaults by strangers versus known assailants in a community
      based population.
AB  - The medical literature has generally supported the view that sexual assaults by
      strangers are more serious and more violent than assaults by people known to the
      victims. This retrospective study was conducted to compare characteristics of
      sexual assaults by strangers and those by people known to the victims in a
      community-based population of women. Study patients were consecutive female
      patients, age 13 years or older, presenting to a sexual assault clinic during a
      40-month study period. The clinic is associated with a university-affiliated
      emergency medicine residency program and is staffed by forensic nurses trained to
      perform medical-legal examinations using colposcopy with nuclear staining. Case
      files of 849 patients were reviewed; the age range was 13 to 82 years (mean, 22.5
      years). Sexual assault by a person known to the victim accounted for 646 (76%)
      cases. The majority of these assailants (68%) were described as acquaintances;
      139 (21%) were current or previous boyfriends or spouses; 33 (5%) involved other
      family members. Sexual assault by a stranger was more likely to occur in the home
      of the victim (43% v 28%, P < .001), involve weapons or physical coercion (58% v
      31%, P < .001), and was associated with more non-genital injuries (61% v 40%, P <
      .001). However, the overall frequency of anogenital trauma (77% v 71%, P = .10),
      the mean number of anogenital injuries (2.0 v 2.3, P = .05), and the types of
      genital trauma were similar in both groups of women. These results demonstrated
      that 71% of the victims of acquaintance rape sustain anogenital trauma and that
      these injuries may be as extensive as those caused by unknown assailants.

PMID- 15520940
TI  - Point of care pregnancy testing provides staff satisfaction but does not change
      ED length of stay.
AB  - Point of care testing (POCT) is widely viewed as possibly improving ED care and
      reducing length of stay (LOS). However reports are mixed, and regulatory barriers
      complicate considerations. We studied a simple urine pregnancy assay (human
      chorionic gonadotropin-HCG). LOS was evaluated when HCG was moved from central
      lab (HCGLab) to POCT (HCGED) in 2 pre-post 3-month periods (958 HCGLab and 1075
      HCGED). HCG patients were compared with a similar control group, and staff
      perceptions were evaluated. There was no change in LOS for HCG patients (36.8 v
      50.85 min, P = .33), although there was one marginal finding of improved LOS for
      patients presenting with abdominal pain diagnosed as pregnant (P = .17). Staff
      (28/53 physicians, 18/81 nurses) reported HCGED as positive. POCT does not
      improve LOS for broad groups of patients, although POCT does change the ED
      environment. Further study is needed to evaluate how the information flow of POCT
      changes patient care.

PMID- 15520941
TI  - The effect of insurance status, race, and gender on ED disposition of persons
      with traumatic brain injury.
AB  - The objective of this study was to assess the effect of insurance status and
      demographic characteristics on ED disposition among patients with traumatic brain
      injury (TBI). Statewide hospital discharge and ED datasets in South Carolina,
      1996-2001, were analyzed by primary or secondary diagnosis of TBI in a
      multivariable logistic regression model. Of 70,671 unduplicated patients with TBI
      evaluated in the ED, 76% were treated and released; 26% had no insurance. The
      strongest predictors of hospital admission were TBI severity and preexisting
      health conditions. However, the uninsured and black females were less likely to
      be hospitalized after adjusting for demographic, clinical, and hospital
      characteristics (odds ratio [OR], 0.52; 95% confidence interval [CI], 0.48-0.55
      and OR, 0.79; CI, 0.72-0.87, respectively). Although this study does not infer
      causality, insurance status, race, and gender were significant predictors of
      hospital admission. These results suggest that inpatient resources are not
      equitably used.

PMID- 15520942
TI  - Use of a radial artery compression device for noninvasive, near-continuous blood
      pressure monitoring in the ED.
AB  - This study's goal was to test a novel device using continuous partial radial
      artery compression for mean arterial pressure (MAP) measurement. A prospective,
      nonblind, convenience-sample trial at a level I center (annual ED census 70,000)
      enrolled 15 adults with indwelling radial arterial catheters and accessible
      contralateral radial pulse. Subjects had MAPs measured simultaneously by test
      device (TEST assessments), oscillometric brachial artery cuff (OSC), and arterial
      line (ART). There was no difference between the three groups' MAP means (P =
      .98). R(2) values for ART/OSC and ART/TEST were 0.96 and 0.95, respectively (P
      <.001). TEST and OSC MAP readings were equally likely (P = 0.66) to be within 5
      mm Hg of ART in both the overall set of 307 MAPs and in the subset of 120 cases
      in which ART MAPs were below 80 (P = .47). The TEST device performed at least as
      well as oscillometric assessment, offering advantages of noninvasive, near
      continuous data.

PMID- 15520943
TI  - Use of the endotracheal bougie introducer for difficult intubations.
AB  - A difficult to intubate patient occurs infrequently in the emergency department.
      The endotracheal tube introducer or gum elastic bougie is a device used by
      British anesthesiologists in difficult airways. The device is inexpensive, has
      few complications and is easy to use. Similar to the Seldinger technique for
      gaining access to a large central vein, the endotracheal tube introducer is used
      to assist in cannulating the trachea and acts like the wire in central vein
      access.

PMID- 15520944
TI  - SARS changes the ED paradigm.
AB  - Severe acute respiratory syndrome (SARS) is an emerging viral infectious disease.
      The SARS outbreak in Singapore started in mid-March 2003. Emergency departments,
      being the primary portal of entry into the hospitals, had to come up with rapid
      strategic changes and modifications to accommodate and manage this public health
      problem effectively. This report discusses the changes in the Department of
      Emergency Medicine at Singapore General Hospital, the largest public, teaching
      and tertiary hospital in Singapore, during this outbreak. It will highlight the
      safety aspects and universal precautions undertaken, the changes to the triage
      system, working hours, admission policies, as well as the fluctuations in the
      patient load.

PMID- 15520945
TI  - Appropriate use of epinephrine in anaphylaxis.
AB  - We are submitting a case-based presentation illustrating medical errors in the
      use of epinephrine for the treatment of anaphylaxis. Readers will learn from
      mistakes made by other emergency caregivers in treating anaphylaxis. The article
      will specifically review the recommended use of epinephrine in the management of
      anaphylaxis. Four patients are presented who were seen in consultation by our
      outpatient allergy service. In all 4 cases, the history was suggestive of an
      episode of anaphylaxis in which emergency care providers mismanaged treatment. In
      2 cases, the patients required ICU care after improperly receiving intravenous
      epinephrine. In the remaining 2 cases, epinephrine use was either omitted or
      significantly delayed in its administration. Our presentation includes a review
      of consensus statements regarding the treatment of anaphylaxis with particular
      regard to the use of epinephrine. We hope that this information will help prevent
      similar errors from harming other patients.

PMID- 15520946
TI  - Use of FAST to prioritize treatment of concomitant penetrating head, chest and
      torso wounds.

PMID- 15520947
TI  - Elevated plasma cyanide level after hydroxocobalamin infusion for cyanide
      poisoning.

PMID- 15520948
TI  - Mesenteric vein thrombosis: abdominal pain in a thrombophile.

PMID- 15520949
TI  - Additional considerations in presumptive brown recluse spider bites and dapsone
      therapy.

PMID- 15520950
TI  - Informing ED patients of the initiation of a psychiatric 72-hours hold.

PMID- 15520951
TI  - Diphenhydramine-associated wide complex dysrhythmia.

PMID- 15520952
TI  - The prevalence and accuracy of medication lists in an elderly ED population.

PMID- 15520953
TI  - Superactivated charcoal.

PMID- 15520954
TI  - Diabetic mastopathy.

PMID- 15520955
TI  - Hemoptysis caused by aortobronchial fistula.

PMID- 15520956
TI  - Patient's perspective on ED asthma education.

PMID- 15520957
TI  - Locoregional thrombolysis in the ED for pulmonary embolism.

PMID- 15520958
TI  - Bilateral nursemaid's elbow.

PMID- 15520959
TI  - Patient preference for emergency physician age and gender.

PMID- 15520960
TI  - CT findings of impending cardiac arrest.

PMID- 15520961
TI  - Epididymal abscess.

PMID- 15520962
TI  - Endotracheal albuterol treatment of acute bronchospasm.

PMID- 15520964
TI  - Hand injuries during a Muslim Sacrifice Festival.

PMID- 15520963
TI  - Epiploic appendagitis mimicking acute cholecystitis.

PMID- 15520965
TI  - Simultaneous upper and lower genitourinary injuries after blunt trauma highlight
      the need for delayed abdominal CT scans.

PMID- 15520966
TI  - Nitroglycerin in the treatment of the serotonin syndrome.

PMID- 15520967
TI  - Research from the Model Spinal Cord Injury Systems: findings from the current 5
      year grant cycle.
AB  - This issue of the Archives of Physical Medicine and Rehabilitation is dedicated
      to current research findings of the Model Spinal Cord Injury Systems (MSCIS)
      program. The MSCIS grants were established by the Rehabilitation Services
      Administration in the 1970s. Now administered by the National Institute on
      Disability and Rehabilitation Research within the Office of Special Education and
      Rehabilitation Services in the US Department of Education, the program has
      included 27 spinal cord injury centers in the United States over the years. In
      the current 5-year grant cycle (2000-2005), there are 16 designated regional
      MSCIS centers. In addition to establishing a comprehensive system of care, the
      grantees contribute patient data to the National Spinal Cord Injury Database
      (which now contains data on 30,532 subjects with follow-up of up to 30 y). In
      addition, the MSCIS grants enable the conduct of site-specific and collaborative
      research projects. To highlight the research findings of the program, the MSCIS
      have produced a special dissemination effort during each of the previous 5 grant
      cycles, with this issue of the Archives representing the latest of these
      endeavors. This article provides a brief history of the MSCIS program and
      highlights the important findings of the 17 original research articles contained
      in this issue.

PMID- 15520968
TI  - A demographic profile of new traumatic spinal cord injuries: change and stability
      over 30 years.
AB  - OBJECTIVE: To evaluate epidemiologic trends in new spinal cord injuries (SCIs) in
      the United States over 3 decades. DESIGN: Consecutive case series. SETTING: Model
      Spinal Cord Injury Systems (MSCIS) facilities. PARTICIPANTS: Persons (N=30,532)
      admitted to MSCIS facilities within 365 days of injury between 1973 and 2003, and
      enrolled in the National Spinal Cord Injury Database. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Data were collected at MSCIS admission and
      rehabilitation discharge. Variables included age, gender, race and ethnic group,
      year of injury, and level and extent of injury. Specific etiologies were grouped
      as motor vehicle collisions (MVCs), violence, falls, sports, and other.
      Demographic and injury severity trends were analyzed by year of injury groupings
      according to decades (1973-1979, 1980-1989, 1990-1999, 2000-2003.) Chi-square
      tests assessed statistical significance. One-way analysis of variance compared
      mean ages. RESULTS: The male/female ratio remained fairly stable at 4:1, but the
      percentage of women increased slightly over time, especially from MVC etiologies
      ( P <.001). Over time, the mean age at injury increased significantly ( P <.001);
      it was 37.7+/-17.5 years in 2000-2003. The majority of cases were white (66.1%).
      Tetraplegia (54.1%) and complete injuries (55.6%) occurred more than paraplegia
      and incomplete injuries, respectively. MVCs (45.6%) remained the most common
      etiology; falls (19.6%) held the second position over violence (17.8%), except
      for the 1990-1999 period when the positions were reversed. Significantly
      increasing percentages of new injuries were seen for SCI due to automobile,
      motorcycle, bicycle, and all-terrain vehicle crashes, blunt object attacks, snow
      skiing, and medical and surgical mishaps. CONCLUSIONS: Many previously seen SCI
      demographic trends continued into the 2000 decade.

PMID- 15520969
TI  - Symptoms of major depression in people with spinal cord injury: implications for
      screening.
AB  - OBJECTIVES: To provide psychometric data on a self-report measure of major
      depressive disorder (MDD) and to determine whether somatic symptoms are
      nonspecific or count toward the diagnosis. DESIGN: Survey. SETTING: Data from the
      National Spinal Cord Injury Statistical Center representing 16 Model Spinal Cord
      Injury Systems. PARTICIPANTS: Eight hundred forty-nine people with spinal cord
      injury who completed a standardized follow-up evaluation 1 year after injury.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The Patient Health
      Questionnaire-9 (PHQ-9), a measure of MDD as defined by the Diagnostic and
      Statistical Manual of Mental Disorders, 4th Edition . We computed descriptive
      statistics on rates of depressive symptoms and probable MDD, evaluated internal
      consistency and construct validity, and analyzed the accuracy of individual items
      as predictors of MDD. RESULTS: Exactly 11.4% of participants met criteria for
      probable MDD. Probable MDD was associated with poorer subjective health, lower
      satisfaction with life, and more difficulty in daily role functioning. Probable
      MDD was not related to most demographic or injury-related variables. Both somatic
      and psychologic symptoms predicted probable MDD. CONCLUSIONS: The PHQ-9 has
      promise as a tool with which to identify probable MDD in people with SCI. Somatic
      symptoms should be counted toward the diagnosis and should alert health care
      providers to the likelihood of MDD. More efficient screening is only one of the
      quality improvement efforts needed to enhance management of MDD.

PMID- 15520970
TI  - Etiology and incidence of rehospitalization after traumatic spinal cord injury: a
      multicenter analysis.
AB  - OBJECTIVES: To examine the frequency and reasons for rehospitalization in persons
      with acute traumatic spinal cord injury (SCI) during follow-up years and to
      examine the association between rehospitalization and demographics, neurologic
      category, payer sources, length of stay (LOS), discharge motor FIM instrument
      score, and discharge residence. DESIGN: Survey design with analysis of cross
      sectional data. SETTING: Model Spinal Cord Injury Systems (MSCIS) centers.
      PARTICIPANTS: Data for 8668 persons with SCI from 16 MSCIS centers entered in the
      National Spinal Cord Injury Statistical Center database between 1995 and 2002.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: MSCIS Forms I and II were
      used to identify the annual incidence, medical complications, and etiologies of
      rehospitalizations reported at 1-, 5-, 10-, 15-, and 20-year follow-ups. RESULTS:
      The leading cause of rehospitalization was diseases of the genitourinary system,
      including urinary tract infections (UTIs). Diseases of the respiratory system
      tended to be more likely in patients with tetraplegia (C1-8 American Spinal
      Injury Association [ASIA] grades A, B, C); whereas patients with paraplegia (T1
      S5 ASIA grades A, B, C) were more likely to be rehospitalized for pressure
      ulcers. The rate of rehospitalization was significantly higher at year 1, 5, and
      20 for those who were discharged to a skilled nursing facility after acute
      rehabilitation. Lower motor score using the FIM was predictive of
      rehospitalization (P=.000). The average LOS per rehospitalization at the year-5
      follow-up was approximately 12 days, which is lower than in past MSCIS reports.
      CONCLUSIONS: Despite improvements in SCI medical management, rehospitalization
      rates remain high, with an increased incidence in conditions associated with the
      genitourinary system (including UTIs), respiratory complications (including
      pneumonia), and diseases of the skin (including pressure ulcers). Acutely injured
      patients need close follow-up to reduce morbidity and rehospitalizations.

PMID- 15520971
TI  - Health status, community integration, and economic risk factors for mortality
      after spinal cord injury.
AB  - OBJECTIVE: To examine the association of health, community integration, and
      economic status with subsequent mortality and life expectancy among persons with
      spinal cord injury. DESIGN: Cohort study. SETTING: Model Spinal Cord Injury
      Systems (MSCIS) hospitals. PARTICIPANTS: A total of 5947 persons injured since
      1973 who were enrolled in the National Spinal Cord Injury Database and who were
      still alive and received an annual evaluation from November 1995 through March
      2002. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Mortality was
      determined by routine follow-up supplemented by information from the Social
      Security Death Index. A logistic regression model based on the full set of
      predictor variables was developed to estimate the chance of dying in any given
      year. RESULTS: After adjusting for demographic characteristics and injury
      severity, health status indicators, measures of community integration, and
      economic status indicators all had relatively small but statistically significant
      effects (20%-70% increases) on the likelihood of dying during the next year.
      Inclusion of these factors may result in higher life expectancy estimates under
      highly favorable conditions. CONCLUSIONS: Whereas previous reports of the MSCIS
      data have identified the life expectancies associated with a particular set of
      demographic (eg, age, gender) and injury-related characteristics (level and
      completeness of injury; ventilator dependence), the current analysis suggests
      that consideration of health, economic, and psychosocial factors may make
      computations of life expectancy more accurate.

PMID- 15520972
TI  - Gender and minority differences in the pain experience of people with spinal cord
      injury.
AB  - OBJECTIVES: To examine gender and minority differences in the prevalence and
      severity of pain in people with traumatic-onset spinal cord injury (SCI) during
      follow-up, and to determine the relation of those differences to demographic
      characteristics, etiology of injury, and level and extent of the lesion. DESIGN:
      Survey and analysis of cross-sectional data using case-control methodology and
      multiple regression methods. SETTING: Model Spinal Cord Injury Systems (MSCIS).
      PARTICIPANTS: A total of 7379 individuals with traumatic-onset SCI from 16 MSCIS
      entered in the National Spinal Cord Injury Statistical Center database between
      1998 and 2002. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Prevalence
      and severity of pain as reported in follow-up surveys. RESULTS: Pain prevalence
      remained fairly stable over time, ranging from 81% at 1 year postinjury to 82.7%
      at 25 years. Pain was no more common in women than in men, nor did pain severity
      scores differ significantly. However, pain prevalence was significantly lower
      among nonwhites, although they tended to report a higher average pain severity
      score when pain was present. Also, people with SCI who were employed when
      injured, who had more than a high school education, and who were not tetraplegic
      reported a higher prevalence of pain. Pain interfered with work more often for
      women and nonwhites during some, but not all, follow-up years, and for those who
      were not employed at the time of interview, for those whose SCI was caused by
      violence, for those with paraplegia, and for those with incomplete SCI.
      CONCLUSIONS: Pain is a common and significant problem for the majority of people
      with SCI. It may interfere less frequently with work over time, which suggests
      that an adaptive process may be occurring. Gender differences in the pain
      experience did not emerge, but nonwhites tended to have a lower prevalence of
      pain. If pain was present, nonwhites tended to report more severe pain than did
      whites. Further research is needed to delineate the possible psychosocial and
      biomedical causes of these findings.

PMID- 15520973
TI  - Race, employment, and spinal cord injury.
AB  - OBJECTIVES: To examine issues of employment and race for persons with spinal cord
      injury (SCI), by assessing the type of work that was being done before and after
      injury and by placing this in the context of patterns for the general population.
      DESIGN: Retrospective, cross-sectional analysis. SETTING: Centers funded as part
      of the federally sponsored Model Spinal Cord Injury Systems (MSCIS) Project.
      PARTICIPANTS: Two samples: 5925 African Americans and whites with SCI who are
      part of the MSCIS and a subset of 577 people with SCI. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Demographic information, occupational status,
      employment rate, job census codes, Craig Hospital Assessment and Reporting
      Technique-Short Form, and Satisfaction With Life Scale. RESULTS: Racial
      disparities were found in employment rates before injury and at 1, 5, 10, 15, and
      20 years after SCI. Differences were also found in the types of jobs that were
      held before SCI with patterns for participants similar to those of African
      Americans and whites in the general population. No differences were found in the
      types of jobs held by African Americans and whites with SCI at 1 year after
      injury. After injury, African Americans had lower economic self-sufficiency
      scores, regardless of employment status, and lower social integration scores
      among those who were not employed. CONCLUSIONS: Racial disparities found in
      employment patterns among persons with SCI mirrored patterns among the general
      population.

PMID- 15520974
TI  - Environmental factors and their role in participation and life satisfaction after
      spinal cord injury.
AB  - OBJECTIVES: To investigate environmental barriers reported by people with spinal
      cord injury (SCI), and to determine the relative impact of environmental barriers
      compared with demographic and injury characteristics and activity limitations in
      predicting variation in participation and life satisfaction. DESIGN: Cross
      sectional, follow-up survey. SETTING: Individuals rehabilitated at 16 federally
      designated Model Spinal Cord Injury Systems of care, now living in the community.
      PARTICIPANTS: People with SCI (N=2726) who completed routine follow-up research
      interviews between 2000 and 2002. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: The Craig Hospital Inventory of Environmental Factors-Short Form (CHIEF
      SF), the Craig Handicap Assessment and Reporting Technique-Short Form, and the
      Satisfaction With Life Scale. RESULTS: The top 5 environmental barriers reported
      by subjects with SCI, in descending order of importance, were the natural
      environment, transportation, need for help in the home, availability of health
      care, and governmental policies. The CHIEF-SF subscales accounted for only 4% or
      less of the variation in participation; they accounted for 10% of the variation
      in life satisfaction. CONCLUSIONS: The inclusion of environmental factors in
      models of disability was supported, but were found to be more strongly related to
      life satisfaction than to societal participation.

PMID- 15520975
TI  - Metric properties of the ASIA motor score: subscales improve correlation with
      functional activities.
AB  - OBJECTIVE: To apply item response theory (IRT) methods to neurologic and
      functional scales to determine the value of using American Spinal Injury
      Association (ASIA) motor subscores and ability estimates, rather than total ASIA
      motor scores, to predict motor FIM instrument scores. DESIGN: Secondary analysis
      of prospectively collected data. SETTING: Model Spinal Cord Injury Systems
      centers. PARTICIPANTS: People with traumatic spinal cord injury (SCI) (N=4338)
      discharged from inpatient rehabilitation between January 1, 1994, and March 31,
      2003. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Total discharge motor
      FIM scores, FIM subscale scores, and IRT-derived ability estimates of motor FIM
      scores. RESULTS: Use of separate ASIA upper-extremity and lower-extremity motor
      scores improved prediction of motor FIM scores over that of total ASIA motor
      score (R(2) for motor FIM score, .71 vs .59). Use of IRT-based ability estimates
      derived by applying a 2-parameter graded response model to the raw scores,
      however, did not improve prediction of motor FIM scores above that of the ASIA
      motor subscale scores. CONCLUSIONS: Consistent with the metric properties of the
      ASIA motor score, and with recent models of disablement, impairment in SCI is
      more accurately characterized by using separate ASIA upper- and lower-extremity
      motor scores than by using a single motor score. Use of subscores for impairment
      should improve prediction of functional abilities and enhance more complex models
      of disability.

PMID- 15520976
TI  - Late neurologic recovery after traumatic spinal cord injury.
AB  - OBJECTIVE: To present Model Spinal Cord Injury System (MSCIS) data on late
      neurologic recovery after 1 year after spinal cord injury (SCI). DESIGN:
      Longitudinal study of neurologic status as determined by annual evaluations at 1
      and 5 years postinjury. SETTING: MSCIS centers contributing data on people with
      traumatic SCI to the National Spinal Cord Injury Statistical Center database.
      PARTICIPANTS: People with traumatic SCI (N=987) admitted to an MSCIS between 1988
      and 1997 with 1- and 5-year follow-up examinations. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: American Spinal Injury Association (ASIA)
      Impairment Scale (AIS) classification, motor index scores (MIS), motor level, and
      neurologic level of injury (NLI), measured and compared for changes over time.
      RESULTS: The majority of subjects (94.4%) who had a neurologically complete
      injury at 1 year remained complete at 5 years postinjury, with 3.5% improving to
      AIS grade B, and up to 1.05% each improving to AIS grades C and D. There was a
      statistically significant change noted for MIS. There were no significant changes
      for the motor level and NLI over 4 years; however, approximately 20% of subjects
      improved their motor level and NLI. People with complete and incomplete injuries
      had similar improvements in motor level, but subjects with an incomplete injury
      had a greater chance of improvement in NLI and MIS. CONCLUSIONS: There was a
      small degree of neurologic recovery (between 1 and 5 y postinjury) after a
      traumatic SCI. Late conversion, between 1 and 5 years, from a neurologically
      complete to an incomplete injury occurred in 5.6% of cases, but in only up to
      2.1% was there a conversion from motor complete to motor incomplete status.
      Limitations of this study included changes in the ASIA classification during the
      study and in the intra- and interrater reliability typically seen in longitudinal
      studies of the ASIA standards. Functional changes were not studied. Knowledge of
      the degree of late recovery may help in analyzing newer interventions to enhance
      recovery.

PMID- 15520977
TI  - Outcomes of early surgical management versus late or no surgical intervention
      after acute spinal cord injury.
AB  - OBJECTIVE: To compare neurologic, medical, and functional outcomes of patients
      with acute spinal cord injury (SCI) undergoing early (<24 h and 24-72 h) and late
      (>72 h) surgical spine intervention versus those treated nonsurgically. DESIGN:
      Retrospective case series comparing outcomes by surgical and nonsurgical groups
      during acute care, rehabilitation, and at 1-year follow-up. SETTING: Multicenter
      National Spinal Cord Injury Database. PARTICIPANTS: Consecutive patients with
      acute, nonpenetrating, traumatic SCI from 1995 to 2000, admitted in the first 24
      hours after injury. Surgical spinal intervention was likely secondary to nature
      of injury and the need for spinal stabilization. Interventions Not applicable.
      MAIN OUTCOME MEASURES: Changes in neurologic outcomes (motor and sensory levels,
      motor index score, American Spinal Injury Association [ASIA] Impairment Scale
      [AIS]), medical complications (pneumonia and atelectasis, deep vein thrombosis
      and pulmonary embolism, pressure ulcers, autonomic dysreflexia,
      rehospitalization), and functional outcomes (acute and rehabilitation length of
      stay [LOS], hospital charges, FIM instrument score, FIM motor efficiency scores).
      RESULTS: Subjects in the early surgery group were more likely ( P <.05) to be
      women, have paraplegia, and have SCI caused by motor vehicle collisions. The
      nonsurgical group was more likely ( P <.05) to have an older mean age and more
      incomplete injuries. ASIA motor index improvements (from admission to 1-y follow
      up) were more likely ( P <.05) in the nonsurgical groups, as compared with the
      surgical groups. Those with late surgery had significantly ( P <.05) increased
      acute care and total LOS and hospital charges along with higher incidence of
      pneumonia and atelectasis. No differences between groups were found for changes
      in neurologic levels, AIS grade, or FIM motor efficiency. CONCLUSIONS: ASIA motor
      index improvements were noted in the nonsurgery group, though likely related to
      increased incompleteness of injuries within this group. Early versus late spinal
      surgery was associated with shorter LOS and reduced pulmonary complications,
      however, no differences in neurologic or functional improvements were noted
      between early or late surgical groups.

PMID- 15520978
TI  - Effects of gender on neurologic and functional recovery after spinal cord injury.
AB  - OBJECTIVE: To assess gender differences in neurologic and functional outcome
      measures in persons with spinal cord injury (SCI). DESIGN: Case series. SETTINGS:
      Model Spinal Cord Injury Systems (MSCIS) throughout the United States.
      PARTICIPANTS: People (N=14,433) admitted to an MSCIS within 30 days of injury.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Improvement in American
      Spinal Injury Association (ASIA) motor index score, ASIA Impairment Scale, level
      of injury, and FIM instrument scores after SCI. RESULTS: When examining subjects
      grouped by severity of injury, changes in ASIA motor index total scores, from
      system admission to 1-year anniversary, were significantly greater for women than
      men with either complete ( P =.035) or incomplete ( P =.031) injuries. Functional
      comparison of men and women, using the FIM motor subscale, revealed that men had
      higher FIM motor scores at rehabilitation discharge among those with motor
      complete injuries, except for those with C1-4 and C6 neurologic levels. Women
      with motor-incomplete high tetraplegia (C1-4 levels) had higher discharge FIM
      motor scores than did similarly afflicted men. There were no significant
      differences in FIM motor scores among men and women with other levels of motor
      incomplete SCI. CONCLUSIONS: Gender differences in SCI were seen in several
      areas. Women may have more natural neurologic recovery than men; however, for a
      given level and degree of neurologic injury, men tend to do better functionally
      than women at time of discharge from rehabilitation. Future prospective study of
      the effects of estrogen on neurologic recovery and the effects of gender on
      functional potential are recommended.

PMID- 15520979
TI  - Patterns of alcohol and substance use and abuse in persons with spinal cord
      injury: risk factors and correlates.
AB  - OBJECTIVE: To investigate patterns of alcohol consumption and abuse and substance
      use among persons with spinal cord injury (SCI), relating these patterns to
      demographic and injury-related characteristics, as well as to key medical and
      psychosocial outcomes. DESIGN: Retrospective cross-sectional. PARTICIPANTS:
      Subjects with traumatic SCI (N=3041) with dates of injury between June 6, 1975,
      and June 23, 2002, who were interviewed between November 2000 and March 2003.
      SETTING: Sixteen Model Spinal Cord Injury Systems participating in this
      collaborative study during the 2000-2005 grant cycle. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Alcohol consumption, substance use, CAGE
      questionnaire, Satisfaction With Life Scale, Craig Handicap Assessment Reporting
      Technique, and pain. Data were analyzed using chi-square tests, analysis of
      variance, analysis of covariance, and logistic regression models. RESULTS:
      Fourteen percent of the subjects were classified as likely to have an alcohol
      abuse issue, based on the CAGE, and 11% reported using illegal drugs or
      prescription medications for nonmedical reasons. Demographic and injury
      characteristics were associated with alcohol consumption patterns, abuse, and
      substance use. At-risk drinkers and substance users tended to be younger, single,
      male, and less educated. Those who were CAGE positive and substance users
      reported more pain and lower satisfaction with life. Persons who drank without
      indication of problem drinking had superior occupation outcomes. Pressure ulcers
      were associated with substance use. CONCLUSIONS: Alcohol abuse and substance use
      were related to a number of adverse outcomes. The specific role of drinking with
      increased work activity deserves further exploration.

PMID- 15520980
TI  - Aging with spinal cord injury: changes in selected health indices and life
      satisfaction.
AB  - OBJECTIVES: To document the impact of age, age at injury, years postinjury, and
      injury severity on changes over time in selected physical and psychosocial
      outcomes of people aging with spinal cord injury (SCI), and to identify the best
      predictors of these outcomes. DESIGN: Retrospective cross-sectional and
      longitudinal examination of people with SCI. SETTING: Follow-up of people who
      received initial rehabilitation in a regional Model Spinal Cord Injury System.
      PARTICIPANTS: People who meet the inclusion criteria for the National Spinal Cord
      Injury Database were studied at 5, 10, 15, 20, and 25 years postinjury.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Number of pressure ulcers,
      number of times rehospitalized, number of days rehospitalized, perceived health
      status, satisfaction with life, and pain during the most recent follow-up year.
      RESULTS: The number of days rehospitalized and frequency of rehospitalizations
      decreased and the number of pressure ulcers increased as time passed. For the
      variables of pressure ulcers, poor perceived health, the perception of pain and
      lower life satisfaction, the best predictor of each outcome was the previous
      existence or poor rating of that same outcome. CONCLUSIONS: Common complications
      of SCI often herald the recurrence of those same complications at a later point
      in time, highlighting the importance of early intervention to prevent future
      health and psychosocial difficulties.

PMID- 15520981
TI  - Assessing the influence of wheelchair technology on perception of participation
      in spinal cord injury.
AB  - OBJECTIVE: To investigate factors related to the wheelchair, impairment, and
      environment that affect perception of participation of persons with spinal cord
      injury (SCI) in activities performed in 3 settings: in the home, in the
      community, and during transportation. DESIGN: Cross-sectional study. SETTING:
      Research centers and a specialized assistive technology (AT) clinic in Pittsburgh
      (Pitt). Research centers and community-based rehabilitation technology suppliers
      in Saint Louis (SL). PARTICIPANTS: Seventy wheelchair users with SCI.
      INTERVENTIONS: Subjects from Pitt and SL completed a written survey of AT usage
      in daily activities. MAIN OUTCOME MEASURES: Subjects were asked 5 questions
      within each setting (home, community, transportation) related to their perceived
      reason for functional limitations. RESULTS: The wheelchair was the most commonly
      cited factor limiting participation, followed by physical impairment and physical
      environment. Twenty-one percent of subjects with paraplegia reported pain as a
      limiting factor for their transportation use, significantly more (P=.047) than
      subjects with tetraplegia (3%). A trend (P=.099) was seen toward a higher
      percentage of subjects with tetraplegia (tetraplegia, 7%; paraplegia, 3%)
      reporting lack of equipment as a limiting factor for use of transportation.
      Differences were also seen across sites. CONCLUSIONS: The wheelchair was the most
      commonly cited limiting factor, followed by physical impairment and physical
      environment. The wheelchair is the most important mobility device used by persons
      with SCI and the one that users most associate with barriers.

PMID- 15520982
TI  - Demographic and socioeconomic factors associated with disparity in wheelchair
      customizability among people with traumatic spinal cord injury.
AB  - OBJECTIVES: To determine if a standard of care for wheelchair provision exists
      within the participating centers and if there is disparity in wheelchair
      customizability among the study sample. DESIGN: Convenience sample survey.
      SETTING: Thirteen Model Spinal Cord Injury Systems that provide comprehensive
      rehabilitation for people with traumatic spinal cord injury (SCI) and that are
      part of the national database funded through the US Department of Education.
      PARTICIPANTS: A total of 412 people with SCI who use wheelchairs over 40 hours a
      week. INTERVENTION: Survey information was obtained from subjects via telephone
      and in-person interviews and from the national database. Collected information
      included age, race, education, level of injury, and wheelchair funding source.
      MAIN OUTCOME MEASURES: Number and type (manual or power) of wheelchairs.
      Wheelchair customizability as defined by design features (eg, adjustable axle
      position, programmable controls). RESULTS: Ninety-seven percent of manual
      wheelchair users and 54% of power wheelchair users had customizable wheelchairs.
      No power wheelchair user received a wheelchair without programmable controls.
      Minorities with low socioeconomic backgrounds (low income, Medicaid/Medicare
      recipients, less educated) were more likely to have standard manual and standard
      programmable power wheelchairs. Older subjects were also more likely to have
      standard programmable power wheelchairs. CONCLUSIONS: The standard of care for
      manual wheelchair users with SCI is a lightweight and customizable wheelchair.
      The standard of care for power wheelchairs users has programmable controls.
      Unfortunately, socioeconomically disadvantaged people were less likely to receive
      customizable wheelchairs.

PMID- 15520983
TI  - Impact of a pushrim-activated power-assisted wheelchair on the metabolic demands,
      stroke frequency, and range of motion among subjects with tetraplegia.
AB  - OBJECTIVES: To determine differences in metabolic demands, stroke frequency, and
      upper-extremity joint range of motion (ROM) during pushrim-activated power
      assisted wheelchair (PAPAW) propulsion and traditional manual wheelchair
      propulsion among subjects with tetraplegia. DESIGN: Repeated measures. SETTING: A
      biomechanics laboratory within a Veterans Affairs medical center. PARTICIPANTS:
      Fifteen full-time manual wheelchair users who had sustained cervical-level spinal
      cord injuries. INTERVENTIONS: Participants propelled both their own manual
      wheelchairs and a PAPAW through 3 different resistances (slight, 10W; moderate,
      12W; high, 14W) on a wheelchair dynamometer. Each propulsion trial was 3 minutes
      long. MAIN OUTCOME MEASURES: Primary variables that were compared between the 2
      wheelchairs were participants mean steady-state oxygen consumption, ventilation,
      heart rate, mean stroke frequency, and maximum upper-extremity joint ROM.
      RESULTS: When using the PAPAW, participants showed a significant ( P <.05)
      decrease in mean oxygen consumption and ventilation throughout all trials. Mean
      heart rate was significantly lower when using the PAPAW for the high resistance
      trial. Stroke frequency was significantly lower when using the PAPAW for the
      slight and moderate resistances. Overall joint ROM was significantly lower when
      using the PAPAW. CONCLUSIONS: For subjects with tetraplegia, PAPAWs reduce the
      energy demands, stroke frequency, and overall joint ROM when compared with
      traditional manual wheelchair propulsion.

PMID- 15520984
TI  - Patterns of Internet use by persons with spinal cord injuries and relationship to
      health-related quality of life.
AB  - OBJECTIVES: To examine patterns of computer and Internet use among persons with
      spinal cord injuries (SCI) and to assess the relationship between Internet use
      and health-related quality of life (HRQOL). DESIGN: Cross-sectional survey
      design. SETTING: National Model Spinal Cord Injury Systems. PARTICIPANTS: People
      with SCI enrolled in a national database. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Patterns of Internet use and relationship to HRQOL indicators:
      self-perceived health status, health status compared with 1 year ago, severity of
      depression, social integration score, occupation score, contacts with friends,
      business contacts, and satisfaction with life. RESULTS: Most subjects owned
      computers, had Internet access, and used the Internet regularly-primarily for
      email, disability and health information, and shopping. Bivariate analysis
      revealed significant differences in Internet access based on sociodemographics,
      particularly among subjects with less education and among African Americans and
      Hispanics. In initial univariate analysis, most HRQOL indicators were
      significantly better for Internet users; once sociodemographic factors were
      included, 4 indicators remained significant. CONCLUSIONS: Complex factors
      contribute to Internet access among people with SCI, with more barriers among
      specific subgroups. A significant HRQOL benefit from Internet use is suggested.
      Targeted interventions and studies of usage patterns are recommended.

PMID- 15520985
TI  - Triceps denervation as a predictor of elbow flexion contractures in C5 and C6
      tetraplegia.
AB  - OBJECTIVE: To determine whether the existence of elbow flexion contractures in
      persons with C5 or C6 tetraplegia is related to a lack of residual voluntary
      triceps function and triceps denervation (ie, lower motoneuron damage). DESIGN: A
      retrospective study of impairment data from 74 arms to identify the incidence of
      elbow flexion contractures and the contributing factors toward this deformity.
      SETTING: Five spinal cord injury (SCI) rehabilitation centers in the United
      States, 1 in England, and 1 in Australia. PARTICIPANTS: Forty-three subjects with
      motor complete C5 or C6 traumatic SCI. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Active and passive elbow extension, triceps voluntary muscle
      strength, and triceps response to electric stimulation. RESULTS: Subjects with
      weak voluntary triceps had significantly fewer and less severe elbow flexion
      contractures than those with paralyzed triceps ( P =.024). Subjects with
      completely denervated triceps (ie, no response to electric stimulation) had
      significantly more elbow flexion contractures than subjects with even a weak
      response to electric stimulation ( P =.003). Overall, 51% of the arms could not
      be passively extended to zero. Forty-six percent of the arms classified as C5
      lacked full passive elbow extension, compared with 63% of the arms classified as
      C6 ( P =.302). CONCLUSIONS: A relationship has been found between elbow flexion
      contractures and lack of residual voluntary triceps and triceps denervation in
      subjects with C5 or C6 tetraplegia. There should be a greater awareness of the
      elbow flexion contractures that may develop as a result of this relationship. A
      better understanding of this deformity and its characteristics can lead to more
      effective clinical treatment and prevention strategies.

PMID- 15520986
TI  - Inactivated influenza vaccination for people with spinal cord injury.
AB  - OBJECTIVE: To examine the antibody responses of people with spinal cord injury
      (SCI) to the commercially available trivalent influenza vaccine. DESIGN:
      Prospective trial of patients and controls. SETTING: Veterans Affairs medical
      center. PARTICIPANTS: Forty people with SCI and 40 able-bodied subjects.
      INTERVENTION: Intramuscular administration of inactivated influenza vaccine. MAIN
      OUTCOME MEASURES: Antibody responses were determined by using the standard
      hemagglutination-inhibition test before and 4 weeks after vaccination. Serum
      antibody responses were assessed as follows: (1) percentage of each cohort
      achieving a 4-fold or greater rise in antibody titer, (2) percentage of each
      cohort achieving a postvaccination antibody titer of 32 or more, and (3)
      postvaccination geometric mean antibody titers. RESULTS: The serum antibody
      responses to each vaccine antigen were similar for the SCI and the control
      cohorts for the 3 outcomes. Neither the time since injury (</=1 y vs >1 y) nor
      the level of injury (paraplegia vs quadriplegia) affected the vaccine antibody
      responses in the SCI cohort. Subjects older than 65 years had lower
      postvaccination serum antibody levels than those younger than 65 years ( P <.05).
      CONCLUSIONS: People with SCI responded to influenza vaccination in a manner
      similar to able-bodied subjects and would be expected to benefit from
      vaccination.

PMID- 15520987
TI  - A validity study of the WHOQOL-BREF assessment in persons with traumatic spinal
      cord injury.
AB  - OBJECTIVE: To examine the distribution of the scores, internal consistency,
      structure, and discriminant validity of the abbreviated version of the World
      Health Organization Quality of Life (WHOQOL-BREF) assessment in persons with
      traumatic spinal cord injury (SCI). DESIGN: Validation study using multitrait
      analysis and known-groups methods. SETTING: Community and hospital. PARTICIPANTS:
      Persons with SCI (N=111) and non-SCI respondents (N=169). INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURE: The WHOQOL-BREF assessment. RESULTS: The
      frequency distribution of the 4 domains of the WHOQOL-BREF assessment was nearly
      symmetric and showed no floor or ceiling effects. All domains showed good
      internal consistency (Cronbach alpha range, .74-.78), with the exception of the
      social relationships domain (alpha=.54). The 4-domain structure of the WHOQOL
      BREF assessment was confirmed using multitrait analysis. The discriminant
      validity of the WHOQOL-BREF assessment in persons with SCI was satisfactory.
      CONCLUSIONS: The WHOQOL-BREF assessment is suitable for measuring QOL as
      perceived by a person with SCI.

PMID- 15520995
TI  - Disease prevention: the future is here.

PMID- 15520988
TI  - Myotonic dystrophy presenting as new-onset hand weakness and recurrent pneumonia
      in a patient with paraplegia: a case report.
AB  - We describe a previously independent T11 paraplegic patient who had delayed-onset
      hand weakness and recurrent pneumonia caused by myotonic dystrophy. A man in his
      late thirties suffered a thoracic spinal cord injury (SCI) from a gunshot wound
      at the age of 17 years, with resultant T11 American Spinal Injury Association
      class A paraplegia. He lived independently until the age of 36 years when he was
      hospitalized multiple times for pneumonia. During a rehabilitation stay after one
      of the acute hospitalizations, the patient's hand weakness and diffuse muscular
      atrophy were noted. Electrodiagnostic testing was performed, which showed
      myotonic discharges. Genetic testing was consistent with myotonic dystrophy. This
      case shows the importance of considering causes of weakness that affect the
      population as a whole when evaluating a patient with SCI who presents with
      delayed-onset weakness.

PMID- 15520996
TI  - Image of the month.

PMID- 15520997
TI  - Endoscopic balloon dilation compared with sphincterotomy for extraction of bile
      duct stones.
AB  - BACKGROUND AND AIMS: Endoscopic retrograde cholangiopancreatography is commonly
      performed to remove bile duct stones. The aim of this study was to determine
      short-term outcomes of endoscopic balloon dilation of the sphincter of Oddi
      compared with sphincterotomy for stone extraction. METHODS: A randomized,
      controlled multicenter study of 117 patients assigned to dilation and 120 to
      sphincterotomy was performed in a spectrum of clinical and academic practices.
      RESULTS: Characteristics of the patients, procedures, and endoscopists were
      similar except that dilation patients were younger. Procedures were successful in
      97.4% and 92.5% of the dilation and sphincterotomy patients, respectively.
      Overall morbidity occurred in 17.9% and 3.3% ( P < .001; difference, 14.6; 95%
      confidence interval, 7-22.3) and severe morbidity, including 2 deaths, in 6.8%
      and 0%( P < .004; difference, 6.8; 95% confidence interval, 2.3-11.4) for
      dilation and sphincterotomy, respectively. Complications for dilation and
      sphincterotomy, respectively, included: pancreatitis, 15.4% and .8% ( P < .001;
      difference, 14.6; 95% confidence interval, 7.8-21.3); cystic duct fistula, 1.7%
      and 0%; cholangitis, .9% and .8%; perforation, 0% and .8%; and cholecystitis, 0%
      and .8%. There were 2 deaths (1.7%) due to pancreatitis following dilation and
      none with sphincterotomy. The study was terminated at the first interim analysis.
      Dilation patients required significantly more invasive procedures, longer
      hospital stays, and longer time off from normal activities. CONCLUSIONS: In a
      broad spectrum of patients and practices, endoscopic balloon dilation compared
      with sphincterotomy for biliary stone extraction is associated with increased
      short-term morbidity rates and death due to pancreatitis. Balloon dilation of the
      sphincter of Oddi for stone extraction should be avoided in routine practice.

PMID- 15520999
TI  - Computed tomographic colonography without cathartic preparation for the detection
      of colorectal polyps.
AB  - BACKGROUND AND AIMS: We prospectively compared the performance of low-dose
      multidetector computed tomographic colonography (CTC) without cathartic
      preparation with that of colonoscopy for the detection of colorectal polyps.
      METHODS: A total of 203 patients underwent low-dose CTC without cathartic
      preparation followed by colonoscopy. Before CTC, fecal tagging was achieved by
      adding diatrizoate meglumine and diatrizoate sodium to regular meals. No
      subtraction of tagged feces was performed. Colonoscopy was performed 3-7 days
      after CTC. Three readers interpreted the CTC examinations separately and
      independently using a primary 2-dimensional approach using multiplanar
      reconstructions and 3-dimensional images for further characterization.
      Colonoscopy with segmental unblinding was used as reference standard. The
      sensitivity of CTC was calculated both on a per-polyp and a per-patient basis.
      For the latter, specificity, positive predictive values, and negative predictive
      values were also calculated. RESULTS: CTC had an average sensitivity of 95.5%
      (95% confidence interval [CI], 92.1%-99%) for the identification of colorectal
      polyps > or =8 mm. With regard to per-patient analysis, CTC yielded an average
      sensitivity of 89.9% (95% CI, 86%-93.7%), an average specificity of 92.2% (95%
      CI, 89.5%-94.9%), an average positive predictive value of 88% (95% CI, 83.3%
      91.5%), and an average negative predictive value of 93.5% (95% CI, 90.9%-96%).
      Interobserver agreement was high on a per-polyp basis (kappa statistic range, .61
      .74) and high to excellent on a per-patient basis (kappa statistic range, .79
      .91). CONCLUSIONS: Low-dose multidetector CTC without cathartic preparation
      compares favorably with colonoscopy for the detection of colorectal polyps.

PMID- 15521000
TI  - An analysis of the potential impact of computed tomographic colonography (virtual
      colonoscopy) on colonoscopy demand.
AB  - BACKGROUND AND AIMS: There has been much speculation about the potential impact
      on the use of conventional colonoscopy if "virtual" computed tomographic
      colonography (CTC) became a widely accepted modality for colorectal cancer (CRC)
      screening. However, no formal analysis of the impact of CTC on colonoscopy demand
      has been reported. METHODS: A mathematical model to predict colonoscopy demand
      based on several relevant input parameters was constructed. Current national
      colonoscopy practice, estimated using various published reports, was used as the
      foundation to project colonoscopy demand if CTC were implemented as the primary
      CRC screening modality. RESULTS: In the base-case analysis, if CTC were used as
      the primary modality for CRC screening, 1.78 million colonoscopies could be
      eliminated from the total 6.47 million in 2003. Depending on the polyp size
      threshold used to define a CTC study as positive (6 or 10 mm), this loss would be
      partially offset by 1.21 million (6 mm) or .34 million (10 mm) follow-up
      colonoscopies for CTC examinations with positive findings, resulting in a net
      loss of .57 million (8.8% decrease) (6 mm) or 1.44 million (22.3% decrease) (10
      mm). Extensive sensitivity analyses showed that the findings of this model were
      robust and insensitive to most parameters tested but were sensitive to a few
      parameters, including the percentage of CTC examinations with positive findings.
      CONCLUSIONS: Wide-scale implementation of CTC for CRC screening would likely lead
      to a decrease in use of conventional colonoscopy. The percentage of CTC studies
      with positive findings seemed to be a pivotal variable, which would be determined
      in large part by the polyp size ultimately established to define a positive
      finding.

PMID- 15521001
TI  - Risks of clinically significant upper gastrointestinal events with etodolac and
      naproxen: a historical cohort analysis.
AB  - BACKGROUND AND AIMS: Etodolac is a generic nonsteroidal anti-inflammatory drug
      (NSAID). Previous in vitro studies have shown that etodolac is a selective
      inhibitor of cyclooxygenase (COX)-2 with selectivity in between that of other COX
      2 inhibitors such as celecoxib and rofecoxib. However, there are no outcomes data
      assessing clinically significant upper gastrointestinal (CSUGI) events with
      etodolac. METHODS: A historical cohort study was performed at the Dallas Veterans
      Affairs Medical Center in which 16,286 veteran patients (5596 patient-years)
      received etodolac or naproxen during a 3-year period without concurrent use of
      other ulcerogenic drugs other than low-dose aspirin. The primary outcome was the
      CSUGI event rate of the etodolac and naproxen groups without concomitant low-dose
      aspirin. RESULTS: The incidence of CSUGI events was .78% and .24% for naproxen
      and etodolac, respectively. In the NSAID-naive subset, the incidence of CSUGI
      events was .99% and .24% for naproxen and etodolac, respectively. Compared with
      naproxen, etodolac was associated with a reduction in upper gastrointestinal
      events, corresponding to an odds ratio of .39 (95% confidence interval, .20-.76;
      P = .006). Concomitantly used low-dose aspirin increased event rates with
      naproxen 2-fold and etodolac 9-fold. Hence, there was no significant difference
      in gastrointestinal event rates between etodolac and naproxen when low-dose
      aspirin was taken concomitantly. CONCLUSIONS: Etodolac is a generic COX-2
      selective inhibitor that reduces CSUGI events compared with the nonselective
      NSAID naproxen. However, concomitant use of low-dose aspirin negates the
      gastrointestinal safety advantages of etodolac.

PMID- 15521002
TI  - The efficacy of proton pump inhibitors in nonulcer dyspepsia: a systematic review
      and economic analysis.
AB  - BACKGROUND AND AIMS: The evidence that proton pump inhibitor (PPI) therapy
      affects symptoms of nonulcer dyspepsia is conflicting. We conducted a systematic
      review to evaluate whether PPI therapy had any effect in nonulcer dyspepsia and
      constructed a health economic model to assess the cost-effectiveness of this
      approach. METHODS: Electronic searches were performed using the Cochrane
      Controlled Trials Register, MEDLINE, EMBASE, CINAHL, and SIGLE until September
      2002. Dyspepsia outcomes were dichotomized into cured/improved versus same/worse.
      Results were incorporated into a Markov model comparing health service costs and
      benefits of PPI with antacid therapy over 1 year. RESULTS: Eight trials were
      identified that compared PPI therapy with placebo in 3293 patients. The relative
      risk of remaining dyspeptic with PPI therapy versus placebo was .86 (95%
      confidence interval, .78-.95; P = .003, random-effects model) with a number
      needed to treat of 9 (95% confidence interval, 5-25). There was statistically
      significant heterogeneity between trials (heterogeneity chi(2) = 30.05; df = 7; P
      < .001). The PPI strategy would cost an extra US dollar 278/month free from
      dyspepsia if the drug cost US dollar 90/month. If a generic price of US dollar
      19.99 is used, then a PPI strategy costs an extra US dollar 57/month free from
      dyspepsia. A third-party payer would be 95% certain that PPI therapy would be
      cost-effective, provided they were willing to pay US dollar 94/month free from
      dyspepsia. CONCLUSIONS: PPI therapy may be a cost-effective therapy in nonulcer
      dyspepsia, provided generic prices are used.

PMID- 15521003
TI  - Moderate hypothermia in patients with acute liver failure and uncontrolled
      intracranial hypertension.
AB  - BACKGROUND AND AIMS: About 20% of patients with acute liver failure (ALF) die
      from increased intracranial pressure (ICP) while awaiting transplantation. This
      study evaluates the clinical effects and pathophysiologic basis of hypothermia in
      patients with ALF and intracranial hypertension that is unresponsive to standard
      medical therapy. METHODS: Fourteen patients with ALF who were awaiting orthotopic
      liver transplantation (OLT) and had increased ICP that was unresponsive to
      standard medical therapy were studied. Core temperature was reduced to 32 degrees
      C-33 degrees C using cooling blankets. RESULTS: Thirteen patients were
      successfully bridged to OLT with a median of 32 hours (range, 10-118 hours) of
      cooling. They underwent OLT with no significant complications related to cooling
      either before or after OLT and had complete neurologic recovery. ICP before
      cooling was 36.5 +/- 2.7 mm Hg and was reduced to 16.3 +/- .7 mm Hg at 4 hours,
      which was sustained at 24 hours (16.8 +/- 1.5 mm Hg) ( P < .0001). Mean arterial
      pressure and cerebral perfusion pressure increased significantly, and the
      requirement for inotropes was reduced significantly. Hypothermia produced
      sustained and significant reduction in arterial ammonia concentration and its
      brain metabolism, cerebral blood flow, brain cytokine production, and markers of
      oxidative stress. CONCLUSIONS: Moderate hypothermia is an effective and safe
      bridge to OLT in patients with ALF who have increased ICP that is resistant to
      standard medical therapy. Hypothermia reduces ICP by impacting on multiple
      pathophysiologic mechanisms that are believed to be important in its
      pathogenesis. A large multicenter trial of hypothermia in ALF is justified.

PMID- 15521004
TI  - Short-term antiviral efficacy of BILN 2061, a hepatitis C virus serine protease
      inhibitor, in hepatitis C genotype 1 patients.
AB  - BACKGROUND AND AIMS: Novel, potent, and well-tolerated hepatitis C virus (HCV)
      drugs are needed. BILN 2061 is a potent and specific inhibitor of HCV serine
      protease in vitro. Preclinical toxicology data and studies in healthy volunteers
      supported the administration of BILN 2061 to patients with HCV infection.
      METHODS: The antiviral efficacy, pharmacokinetics, and tolerability of 25, 200,
      and 500 mg BILN 2061 twice daily given as monotherapy for 2 days in 31 patients
      infected with chronic genotype 1 HCV infection and with minimal liver fibrosis
      (Ishak score of 0-2) were assessed in a placebo-controlled, double-blind pilot
      study. In 2 subsequent placebo-controlled studies of similar design, 200 mg BILN
      2061 twice daily was administered for 2 days to 10 patients with advanced liver
      fibrosis (Ishak score of 3 or 4) and to 10 patients with compensated cirrhosis
      (Ishak score of 5 or 6). RESULTS: Viral RNA reductions of 2-3 log 10 copies/mL
      were achieved in most of the patients. There was a trend toward a higher number
      of patients receiving 500 mg BILN 2061 achieving a viral RNA reduction > or =3
      log(10) copies/mL as compared with patients receiving 25 mg BILN 2061. Advanced
      fibrosis or compensated cirrhosis did not affect the antiviral efficacy of BILN
      2061. BILN 2061 was well tolerated in all studies. CONCLUSIONS: BILN 2061 is a
      well-tolerated and very active compound that reduced serum viral RNA
      concentrations after 2 days of treatment in patients infected with genotype 1 HCV
      independent of the degree of fibrosis. Nevertheless, further clinical trials are
      on hold pending resolution of animal toxicity issues.

PMID- 15521005
TI  - Occult hepatitis B virus infection in chronic liver disease: full-length genome
      and analysis of mutant surface promoter.
AB  - BACKGROUND AND AIMS: Genome sequence of hepatitis B virus (HBV) from occult
      chronic infection is scarce. Fifty-six (9.4%) of 591 patients seronegative for
      hepatitis B surface antigen (HBsAg) with chronic liver disease were positive for
      HBV DNA. The complete HBV genome from 9 of these patients (S1-S9) and 5 controls
      positive for HBsAg (SWT.1-SWT.5) were analyzed. METHODS: Overlapping genome
      fragment amplification, cloning, and sequencing was performed on these cases.
      Functional analysis of surface promoter was conducted using fusion construct.
      RESULTS: All patients with occult infection except one (S8) had a low viral
      titer. Eight patients had infection with genotype A (S1-S5, SWT.1-2, SWT.5) and 6
      had infection with genotype D (S6-S9, SWT.3-4). S4 and S5.1 of genotype A had the
      characteristic nucleotide deletions in core and pre-S1 region seen in genotype D.
      The major observations in patients with occult HBV infection were as follows:
      frequent quasispecies variation, deletions in pre-S2/S region affecting the
      surface promoters (nt 3025-54) and pre-S protein (S3, S5, S6, S8), truncated
      precore (S6, S8, S7.1) and core (S9) owing to stop signal, alternate start codon
      for the Polymerase gene (S3, S9), and YMDD mutation (S1, S4, S9) in patients not
      on antiviral therapy. HBsAg and core proteins could be shown
      immunohistochemically in 3 of 5 liver biopsy specimens available. The mutant
      surface promoters (pre-S2 and S) on functional analysis showed alterations in
      HBsAg expression. CONCLUSIONS: These changes in the regulatory region with
      possible alterations in the ratio of large and small surface proteins along with
      other mutations in the genome may decrease the circulating HBsAg level
      synergistically, making the immunodetection in serum negative.

PMID- 15521006
TI  - Hepatitis C infection and the increasing incidence of hepatocellular carcinoma: a
      population-based study.
AB  - BACKGROUND AND AIMS: A significant increase in the incidence of hepatocellular
      carcinoma (HCC) has been reported in the United States. The risk factors
      underlying this increase remain unclear. METHODS: By using Surveillance,
      Epidemiology, and End-Results program (SEER)-Medicare-linked data, we conducted a
      population-based study to examine temporal changes in risk factors for patients
      65 years and older diagnosed with HCC between 1993 and 1999. Only patients with
      continuous Medicare enrollment for 2 years before and up to 2 years after HCC
      diagnosis were examined. Univariate and multiple logistic regression analyses
      were used to evaluate changes in risk factors over time (January 1993-June 1996
      and July 1996-December 1999). RESULTS: The age-adjusted incidence of HCC among
      persons 65 years of age and older significantly increased from 14.2 per 100,000
      in 1993 to 18.1 per 100,000 in 1999. We identified 2584 patients with continuous
      Medicare enrollment 2 years before and up to 2 years after HCC diagnosis. The
      proportion of hepatitis C virus (HCV)-related HCC increased from 11% during
      January of 1993 to June of 1996 to 21% during July of 1996 to December of 1999,
      whereas hepatitis B virus (HBV)-related HCC increased from 6% to 11% ( P <
      .0001). In multiple logistic regression analyses that adjusted for age, sex,
      race, and geographic region, the risk for HCV-related HCC and HBV-related HCC
      increased by 226% and 67%, respectively. Idiopathic HCC decreased from 43% to
      39%. This decrease did not fully account for the significant increases observed
      for HCV and HBV. No significant changes over time were observed for alcohol
      induced liver disease, nonspecific cirrhosis, or nonspecific hepatitis.
      CONCLUSIONS: There has been a significant recent increase in HCV- and HBV-related
      HCC. Increasing rates of HCV-related HCC can explain a substantial proportion of
      the reported increase in HCC incidence during recent years.

PMID- 15521007
TI  - No evidence of maternal cell colonization in reverted liver nodules of
      tyrosinemia type I patients.
AB  - BACKGROUND AND AIMS: Hereditary tyrosinemia type I (HTI) is a recessively
      inherited disease caused by a deficiency of fumarylacetoacetate hydrolase (FAH),
      the last enzyme of the tyrosine catabolic pathway. The mosaic pattern of FAH
      expression observed in the livers of >85% of studied patients was shown to result
      from the correction of the mutation in one of the FAH alleles. Bilateral cell
      trafficking can occur between mother and fetus and such an event could be
      responsible for the chimerism observed in some diseases. It also has been
      reported that the liver repopulation observed in a HTI murine model by serial
      transplantation of bone marrow-derived cells was caused by a fusion of these
      cells to host hepatocytes. These observations led us to test the possibility that
      the transfer of nucleated heterozygous maternal cells in the fetal circulation
      could be responsible for the mosaic liver expression of FAH in HTI patients.
      METHODS: We used polymorphic markers of short cytosine-adenine DNA repeats to
      compare DNA from corrected liver sections of 4 HTI patients with DNA from their
      parents' blood. RESULTS: Genotyping showed that only one maternal allele is
      present in DNA isolated from FAH-expressing liver nodules of each proband for at
      least 1 marker. CONCLUSIONS: The corrected liver nodules in HTI patients are not
      of maternal origin and do not support cell trafficking and cell fusion as
      mechanisms of correction of the gene defect in hepatocytes of tyrosinemia
      patients.

PMID- 15521008
TI  - Claudin-1 gene mutations in neonatal sclerosing cholangitis associated with
      ichthyosis: a tight junction disease.
AB  - BACKGROUND AND AIMS: Most human and animal cholestatic disorders are associated
      with changes in hepatocyte cytoskeleton and tight junctions (TJs). These changes
      are usually secondary and nonspecific phenomena, both in intra- and extrahepatic
      cholestasis. Recently, missense mutations in TJ protein 2 (ZO-2) have been
      identified in patients with familial hypercholanemia. In the liver, TJs separate
      bile flow from plasma and are composed of strands of claudins and occludin. We
      previously assigned a syndrome associating ichthyosis and neonatal sclerosing
      cholangitis (NISCH syndrome) to chromosome 3q27-q28. We considered claudin-1 to
      be a strong candidate gene based on its mapping to the minimum interval and on
      the expression pattern of the mouse ortholog. METHODS: The 4 exons and intron
      exon junctions of claudin-1 gene were amplified using standard polymerase chain
      reaction protocols and specific primers. Western blot analysis on cultured
      fibroblasts and immunohistochemistry on liver tissue section were performed using
      rabbit anti-claudin-1 antibodies. RESULTS: We described in 4 patients, of 2
      inbred kindred of Moroccan origin, a 2-bp deletion (200-201 TT) in exon 1 of the
      claudin-1 gene arising in a premature stop codon and resulting in total absence
      of claudin-1 protein in the liver and skin. CONCLUSIONS: Lack of claudin-1 in
      NISCH syndrome may lead to increased paracellular permeability between epithelial
      cells. Bile duct injury may be related to the absence of claudin-1 expression in
      cholangiocytes. Our observation, in conjunction with ZO-2-associated
      hypercholanemia, emphasizes the role played by TJ components in hereditary
      cholestasis.

PMID- 15521009
TI  - Up-regulation of the enzymes involved in prostacyclin synthesis via Ras induces
      vascular endothelial growth factor.
AB  - BACKGROUND AND AIMS: The constitutive activation of Ras is an important step in
      the development and progression of several different cancers and is known to
      increase the level of cyclooxygenase 2 (COX-2). Prostaglandins are the downstream
      bioactive lipid mediators produced by the COX-2 enzyme. We sought to determine
      the role of Ras-induced up-regulation of the enzymes involved in prostacyclin
      biosynthesis in nontransformed rat intestinal epithelial cells (IECs). METHODS:
      Messenger RNA (mRNA) and protein expression were analyzed by Northern and Western
      analysis, respectively, to determine the level of enzymes induced by Ras. In
      vitro assays were used to determine the production of vascular endothelial growth
      factor (VEGF) and prostaglandins as well as the promoter and enzymatic activation
      of the rate-limiting enzyme in prostaglandin production (phospholipase A(2)
      [cPLA(2)]). RESULTS: The inducible expression of Ha-Ras(V12) increased the
      production of prostaglandin (PG)F(2alpha) and prostacyclin by 2- and 13-fold,
      respectively. The induction of Ha-Ras(V12) also up-regulated the mRNA and protein
      levels of cPLA(2), COX-2, and prostacyclin synthase, as well as the promoter and
      enzyme activity of cPLA(2). Furthermore, oncogenic Ras increased the production
      of the pro-angiogenic factor VEGF. The increase of VEGF was abolished after
      treatment with celecoxib, a selective COX-2 inhibitor. The addition of PGI 2
      alone also induced the expression of VEGF. CONCLUSIONS: Inducible Ha-Ras(V12)
      increases the production of PGI(2) through the coordinate up-regulation of
      cPLA(2), COX-2, and prostacyclin synthase (PGIS). The production of PGI(2) leads
      to an increase in the level of the pro-angiogenic factor VEGF, which is known to
      play a crucial role in the regulation of tumor-associated angiogenesis.

PMID- 15521010
TI  - hPepT1 transports muramyl dipeptide, activating NF-kappaB and stimulating IL-8
      secretion in human colonic Caco2/bbe cells.
AB  - BACKGROUND AND AIMS: Bacterial proteoglycan-derived muramyl dipeptide (MDP)
      activates the intracellular NOD2/CARD15 gene product. How intestinal epithelial
      cells take up MDP is poorly understood. We hypothesized that the intestinal
      apical di-/tripeptide transporter, hPepT1, transports MDP, thereby activating
      downstream pathways similar to nuclear factor kappa B (NF-kappaB). METHODS: Time-
      and concentration-dependent (3)H-MDP uptakes were studied in Caco2/bbe (C2) cell
      monolayers where hPepT1 expression was either over- or underexpressed, using an
      inducible adenovirus system or silencing RNA (siRNA), respectively. NF-kappaB
      activation and interleukin (IL)-8 and monocyte chemoattractant protein-1 (MCP-1)
      release were determined by enzyme-linked immunosorbent assay. NOD2/CARD15
      expression was inhibited by siRNA. MDP in human duodenal, cecal, and stool
      samples was measured. RESULTS: MDP, but not its isoforms, inhibited uptake of
      glycosylsarcosine in C2 cells, indicating stereoselective and competitive
      inhibition. Approximately 90% of the MDP was cytosolic, showing uptake rather
      than binding. The K m for MDP uptake was 4.3 mmol/L. Cells overexpressing hPepT1
      showed increased Gly-Sar and MDP uptake, whereas decreased uptake was observed
      after hPepT1 siRNA-inhibition. MDP treatment activated NF-kappaB, resulting in IL
      8 release, an effect blocked by siRNA-inhibited expression of NOD2/CARD15. MDP
      content in cecal and stool samples (in normal subjects) was 20-87 micromol/L, but
      undetectable in duodenal fluid. CONCLUSIONS: In colonic epithelial cells, MDP is
      taken up by hPepT1 and activates NF-kappaB and chemokine production. Because
      hPepT1 expression in chronic colonic inflammation is increased, this may play an
      important role in promoting colonocyte participation in host defense and pathogen
      clearance through increased uptake of MDP.

PMID- 15521011
TI  - H+/amino acid transporter 1 (PAT1) is the imino acid carrier: An intestinal
      nutrient/drug transporter in human and rat.
AB  - BACKGROUND AND AIMS: Amino acid (and related drug) absorption across the human
      small intestinal wall is an essential intestinal function. Despite the revelation
      of a number of mammalian genomes, the molecular identity of the classic Na(+)
      dependent imino acid transporter (identified functionally in the 1960s) remains
      elusive. The aims of this study were to determine whether the recently isolated
      complementary DNA hPAT1 (human proton-coupled amino acid transporter 1), or
      solute carrier SLC36A1, represents the imino acid carrier; the Na(+) -dependent
      imino acid transport function measured at the brush-border membrane of intact
      intestinal epithelia results from a close functional relationship between human
      proton-coupled amino acid transporter-1 and N(+) /H(+) exchanger 3 (NHE3).
      METHODS: PAT1 function was measured in isolation ( Xenopus laevis oocytes) and in
      intact epithelia (Caco-2 cell monolayers and rat small intestine) by measurement
      of amino acid and/or H(+) influx. Tissue and membrane expression of PAT1 were
      determined by reverse-transcription polymerase chain reaction and
      immunohistochemistry. RESULTS: PAT1-specific immunofluorescence was localized
      exclusively to the luminal membrane of Caco-2 cells and human and rat small
      intestine. The substrate specificity of hPAT1 is identical to that of the imino
      acid carrier. In intact epithelia, PAT1-mediated amino acid influx is reduced
      under conditions in which NHE3 is inactive. CONCLUSIONS: The identification in
      intact epithelia of a cooperative functional relationship between PAT1 (H(+)
      /amino acid symport) and NHE3 (N(+) /H(+) exchange) explains the apparent Na +
      dependence of the imino acid carrier in studies with mammalian intestine. hPAT1
      is the high-capacity imino acid carrier localized at the small intestinal luminal
      membrane that transports nutrients (imino/amino acids) and orally active
      neuromodulatory agents (used to treat affective disorders).

PMID- 15521012
TI  - Regeneration of injured intestinal mucosa is impaired in hepatocyte growth factor
      activator-deficient mice.
AB  - BACKGROUND AND AIMS: Hepatocyte growth factor activator (HGFA) is a serum
      proteinase that specifically converts an inactive single-chain form of hepatocyte
      growth factor (HGF) into an active 2-chain form. HGFA is produced in its
      precursor form and then activated in injured tissues. To address the precise role
      of HGFA and to investigate the mechanisms of HGF activation in injured tissues,
      we generated mice deficient in HGFA. METHODS: HGFA-deficient mice were generated
      using targeted gene disruption. The regenerating process of intestinal mucosa
      damaged by oral administration of dextran sodium sulfate (DSS) or by rectal
      administration of acetic acid was examined in both HGFA-deficient and control
      mice. HGF processing activity was analyzed using Western blotting and an HGF
      activation assay. RESULTS: Homozygous mutant mice were viable and fertile without
      obvious abnormalities. When mice were treated with 3% DSS in drinking water for 6
      days followed by distilled water without DSS, 72% of HGFA-deficient mice died
      through day 12 while 75% of control mice survived injury. Similar results were
      also observed in the acetic acid-induced intestinal injury; the survival rate was
      36.6% in HGFA-deficient mice and 84.2% in control mice. In HGFA-deficient mice,
      the injured mucosa was not sufficiently covered by regenerated epithelium and the
      activation of HGF was impaired in the injured colon. CONCLUSIONS: These results
      indicate that HGFA is required for repair of injured intestinal mucosa but is not
      essential for normal development during embryogenesis or after birth.

PMID- 15521013
TI  - Evidence for a new human CYP1A1 regulation pathway involving PPAR-alpha and 2
      PPRE sites.
AB  - BACKGROUND AND AIMS: Cytochrome P450 1A1 catalyzes the degradation of endobiotics
      (estradiol, fatty acids, and so on) and the bioactivation of numerous
      environmental procarcinogens, such as arylamines and polycyclic aromatic
      hydrocarbons, that are found in food. Several peroxisome proliferators and
      arachidonic acid derivatives enhance cytochrome P450 1A1 activity, but the
      mechanisms involved remain unknown. The aim of this work was to study the role of
      peroxisome proliferator-activated receptors in cytochrome P450 1A1 gene
      induction. METHODS: The role of peroxisome proliferator-activated receptor
      transcription factors in cytochrome P450 1A1 induction was assessed by means of
      enzymatic activities, quantitative real-time polymerase chain reaction, gene
      reporter assays, mutagenesis, and electrophoretic mobility shift assay. RESULTS:
      We show that peroxisome proliferator-activated receptor-alpha agonists (WY-14643,
      bezafibrate, clofibrate, and phthalate) induce human cytochrome P450 1A1 gene
      expression, whereas 2,4-thiazolidinedione, a specific peroxisome proliferator
      activated receptor-gamma agonist, represses it. The induction of cytochrome P450
      1A1 transcripts by WY-14643 was associated with a marked increase of
      ethoxyresorufin O -deethylase activity (10-fold at 200 mumol/L). Transfection of
      peroxisome proliferator-activated receptor-alpha complementary DNA enhanced
      cytochrome P450 1A1 messenger RNA induction by WY-14643, although WY-14643 failed
      to activate xenobiotic responsive element sequences. Two peroxisome proliferator
      response element sites were located at positions -931/-919 and -531/-519 of the
      cytochrome P450 1A1 promoter. Their inactivation by directed mutagenesis
      suppressed the inductive effect of WY-14643 on cytochrome P450 1A1 promoter
      activation. Electrophoretic mobility shift assay and chromatin
      immunoprecipitation assay experiments showed that the 2 cytochrome P450 1A1
      peroxisome proliferator response element sites bind the peroxisome proliferator
      activated receptor-alpha/retinoid X receptor-alpha heterodimer. CONCLUSIONS: We
      describe here a new cytochrome P450 1A1 induction pathway involving peroxisome
      proliferator-activated receptor-alpha and 2 peroxisome proliferator response
      element sites, indicating that peroxisome proliferator-activated receptor-alpha
      ligands, which are common environmental compounds, may be involved in
      carcinogenesis.

PMID- 15521014
TI  - Profiling of microdissected gastric epithelial cells reveals a cell type-specific
      response to Helicobacter pylori infection.
AB  - BACKGROUND AND AIMS: Helicobacter pylori colonizes the epithelial lining of the
      human stomach and is associated with disorders ranging from chronic gastritis to
      peptic ulcers and gastric cancer. We have explored the transcriptional response
      of the epithelium globally by applying a whole-genome approach to a murine model
      of infection. METHODS: The 3 major epithelial lineages of the stomach-the
      parietal, mucus-producing, and chief cells-were harvested from cryosections of
      infected and uninfected murine stomachs by laser microdissection and subjected to
      gene expression profiling. The localization and quantity of selected transcripts
      were verified by in situ hybridization and quantitative real-time reverse
      transcription polymerase chain reaction. RESULTS: Each cell type is characterized
      by a transcriptional signature profile. The parietal cell profile is highly
      enriched for factors involved in mitochondrial energy generation, whereas the
      chief cell predominantly expresses digestive enzymes and glycosylation-associated
      proteins. In contrast, the mucus cell signature is distinguished by an abundance
      of cell-surface receptors, signaling molecules, and factors involved in antigen
      presentation. All of these indicate a role in sampling, sensing, and responding
      to environmental stimuli. In line with this biological function, we measured a
      strong transcriptional response to Helicobacter pylori infection only in this
      cell type. The genes that are differentially expressed upon infection are
      implicated in a proinflammatory and mucosal defense response as well as
      modulation of angiogenesis, iron availability, and tumor suppression.
      CONCLUSIONS: Laser microdissection-assisted transcriptional profiling is a useful
      tool to explore the biology of specific cell populations and is sensitive enough
      to measure the transcriptional response to bacterial infection in vivo.

PMID- 15521015
TI  - The lymphotoxin-beta receptor is critical for control of murine Citrobacter
      rodentium-induced colitis.
AB  - BACKGROUND AND AIMS: Lymphotoxin is a tumor necrosis factor-family cytokine.
      Blocking of lymphotoxin alpha 1 beta 2 /lymphotoxin-beta receptor interactions
      prevents experimental colitis in mice, and this suggests a potential treatment
      principle of human inflammatory bowel disease. Infection of mice with Citrobacter
      rodentium serves as an animal model for human infectious colitis induced by
      enteropathogenic Escherichia coli . We studied the role of lymphotoxin alpha 1
      beta 2 /lymphotoxin-beta receptor signaling in Citrobacter rodentium -induced
      colitis. METHODS: Mice with disrupted lymphotoxin alpha 1 beta 2 /lymphotoxin
      beta receptor interactions secondary to gene defects (lymphotoxin-alpha -/- ,
      lymphotoxin-beta -/- , and lymphotoxin-beta receptor -/- ) or treatment with the
      antagonist lymphotoxin-beta receptor-immunoglobulin G fusion protein were
      infected with Citrobacter rodentium . Body weight, fecal excretion of Citrobacter
      rodentium , and disease-related mortality were monitored. Spleen and liver organ
      cultures of mice assessed systemic infection. Intestinal inflammation and
      lymphoid architecture were histologically recorded in the large intestine,
      mesenteric lymph nodes, and spleen of infected mice. RESULTS: Inhibition of
      lymphotoxin alpha 1 beta 2 /lymphotoxin-beta receptor interactions was associated
      with increased severity of Citrobacter rodentium -induced colitis, as indicated
      by increased disease-related mortality, more severe weight loss, intestinal
      bacterial abscesses, and a higher burden of Citrobacter rodentium in the spleen
      and liver of -/- and lymphotoxin-beta receptor-immunoglobulin G-treated mice.
      There was a reduction of CD11c + dendritic cells in the spleen of naive and
      infected -/- and lymphotoxin-beta receptor-immunoglobulin G-treated mice. In
      infected lymphotoxin-beta receptor -/- mice, anti- Citrobacter rodentium
      immunoglobulin G2a levels were decreased, whereas immunoglobulin G1 levels were
      increased. Citrobacter rodentium -induced interleukin-4 secretion was increased
      in lymphotoxin-beta receptor -/- mice. CONCLUSIONS: Lymphotoxin alpha 1 beta 2
      /lymphotoxin-beta receptor interactions are critical for immunity against
      Citrobacter rodentium in mice. Impaired anti-enteropathogenic Escherichia coli
      immunity may be anticipated in anti-lymphotoxin-beta receptor-directed therapy
      for human inflammatory bowel disease.

PMID- 15521016
TI  - Probiotics inhibit nuclear factor-kappaB and induce heat shock proteins in
      colonic epithelial cells through proteasome inhibition.
AB  - BACKGROUND AND AIMS: The extent and severity of mucosal injury in inflammatory
      bowel diseases are determined by the disequilibrium between 2 opposing processes:
      reparative and cytoprotective mechanisms vs. inflammation-induced injury.
      Probiotics may provide clinical benefit by ameliorating colitis; however, their
      mechanisms of action remain largely unknown. Our objective was to investigate
      microbial-epithelial interactions that could explain the beneficial therapeutic
      effects of probiotics. METHODS: The effect of VSL#3-conditioned media on the
      nuclear factor-kappaB pathway in young adult mouse colonic epithelial cells was
      assessed by using monocyte chemoattractant protein-1 enzyme-linked immunosorbent
      assays; IkappaBalpha, IkappaBbeta, and p105 immunoblot analysis; and nuclear
      factor-kappaB luciferase reporter gene and proteasome assays. Effects on heat
      shock proteins were determined by electrophoretic mobility shift assay and
      immunoblot for heat shock proteins 25 and 72 in young adult mouse colonic cells.
      Cytoprotection against oxidant injury was determined by chromium 51 release and
      filamentous and globular actin assays. RESULTS: VSL#3 produces soluble factors
      that inhibit the chymotrypsin-like activity of the proteasome in gut epithelial
      cells. Proteasome inhibition is an early event that begins almost immediately
      after exposure of the epithelial cells to the probiotic-conditioned media. In
      addition, these bacteria inhibit the proinflammatory nuclear factor-kappaB
      pathway through a mechanism different from the type III secretory mechanisms
      described for other nonpathogenic enteric flora. They also induce the expression
      of cytoprotective heat shock proteins in intestinal epithelial cells.
      CONCLUSIONS: The resulting inhibition of nuclear factor-kappaB and increased
      expression of heat shock proteins may account for the anti-inflammatory and
      cytoprotective effects reported for probiotics and may be a novel mechanism of
      microbial-epithelial interaction. These effects seem to be mediated through the
      common unifying mechanism of proteasome inhibition.

PMID- 15521017
TI  - Ischemic preconditioning protects hepatocytes via reactive oxygen species derived
      from Kupffer cells in rats.
AB  - BACKGROUND AND AIMS: Hepatic ischemic preconditioning decreases sinusoidal
      endothelial cell injury and Kupffer cell activation after cold
      ischemia/reperfusion, leading to improved survival of liver transplant recipients
      in rats. Ischemic preconditioning also protects livers against warm
      ischemia/reperfusion injury, in which hepatocyte injury is remarkable. We aimed
      to determine whether ischemic preconditioning directly protects hepatocytes and
      to elucidate its mechanisms. METHODS: Rats were injected with gadolinium chloride
      to deplete Kupffer cells or with N -acetyl- l -cysteine, superoxide dismutase, or
      catalase to scavenge reactive oxygen species. Livers were then preconditioned by
      10 minutes of ischemia and 10 minutes of reperfusion. Subsequently, livers were
      subjected to 40 minutes of warm ischemia and 60 minutes of reperfusion in vivo or
      in a liver perfusion system. In other rats, livers were preconditioned by
      H(2)O(2) perfusion instead of ischemia. In the other experiments, livers were
      perfused with nitro blue tetrazolium to detect reactive oxygen species formation.
      RESULTS: Ischemic preconditioning decreased injury in hepatocytes, but not in
      sinusoidal endothelial cells. Kupffer cell depletion itself did not change
      hepatocyte injury after ischemia/reperfusion, indicating no contribution of
      Kupffer cells to ischemia/reperfusion injury. However, Kupffer cell depletion
      reversed hepatoprotection by ischemic preconditioning. Reactive oxygen species
      formation occurred in Kupffer cells after ischemic preconditioning. Scavenging of
      reactive oxygen species reversed the effect of ischemic preconditioning, and
      H(2)O(2) preconditioning mimicked ischemic preconditioning. CONCLUSIONS: Ischemic
      preconditioning directly protected hepatocytes after warm ischemia/reperfusion,
      which is not via suppression of changes in sinusoidal cells as in cold
      ischemia/reperfusion injury. This hepatocyte protection was mediated by reactive
      oxygen species produced by Kupffer cells.

PMID- 15521018
TI  - The nuclear receptor SHP mediates inhibition of hepatic stellate cells by FXR and
      protects against liver fibrosis.
AB  - BACKGROUND AND AIMS: The farnesoid X receptor (FXR) is an endogenous sensor for
      bile acids and inhibits bile acid synthesis by inducing small heterodimer partner
      (SHP) gene expression. The aim of this study was to investigate whether FXR is
      expressed by and modulates function of hepatic stellate cells (HSCs). METHODS:
      The antifibrotic activity of FXR ligand was tested in 2 rodent models: the
      porcine serum and bile duct ligation (BDL). RESULTS: Twelve-week administration
      of 1-10 mg/kg 6-ethyl chenodeoxycholic acid (6-ECDCA), a synthetic FXR ligand, to
      porcine serum-treated rats prevented liver fibrosis development and reduced liver
      expression of alpha1(I) collagen, TGF-beta1 and alpha-SMA mRNA by approximately
      90%. Therapeutic administration of 6-ECDCA, 3 mg/kg, to BDL rats reduced liver
      fibrosis and alpha1(I) collagen, transforming growth factor (TGF)-beta1, alpha
      SMA, and tissue metalloproteinase inhibitor (TIMP)-1 and 2 messenger RNA (mRNA)
      by 70%-80%. No protection was observed in BDL rats treated with CDCA, 3 mg/kg,
      and ursodeoxycholic acid, 15 mg/kg. FXR expression was detected in HSCs. Exposure
      of HSCs to FXR ligands caused a 3-fold increase of SHP, reduced alpha1(I)collagen
      and TGF-beta1 by approximately 60%-70% and abrogates alpha1(I) collagen mRNA up
      regulation induced by thrombin and TGF-beta1. By retrovirus infection and small
      interference RNA, we generated SHP overexpressing and SHP-deficient HSC-T6. Using
      these cell lines, we demonstrated that SHP binds JunD and inhibits DNA binding of
      adaptor protein (AP)-1 induced by thrombin. CONCLUSIONS: By demonstrating that an
      FXR-SHP regulatory cascade promotes resolution of liver fibrosis, this study
      establish that FXR ligands might represent a novel therapeutic option to treat
      liver fibrosis.

PMID- 15521020
TI  - Negative regulation of liver regeneration by innate immunity (natural killer
      cells/interferon-gamma).
AB  - BACKGROUND AND AIMS: Hepatic lymphocytes are composed mainly of natural killer
      (NK) cells and NKT cells, which play key roles in innate immune responses against
      pathogens and tumors in the liver. This report analyzes the effects of activation
      of innate immunity by viral infection or the toll-like receptor 3 (TLR3) ligand
      on liver regeneration. METHODS: The partial hepatectomy (PHx) method was used as
      a model of liver regeneration. Murine cytomegalovirus (MCMV) infection and the
      TLR3 ligand polyinosinic-polycytidylic acid [poly(I:C)] were used to activate
      innate immunity. RESULTS: NK cells are activated after PHx, as evidenced by
      producing interferon (IFN)-gamma. Infection with MCMV or injection of poly(I:C)
      further activates NK cells to produce IFN-gamma and attenuates liver regeneration
      in the PHx model. Depletion of NK cells or disruption of either the IFN-gamma
      gene or the IFN-gamma receptor gene enhances liver regeneration and partially
      abolishes the negative effects of MCMV and polyI:C on liver regeneration, whereas
      NKT cells may only play a minor role in suppression of liver regeneration.
      Adoptive transfer of IFN-gamma +/+ NK cells, but not IFN-gamma -/- NK cells,
      restores the ability of polyI:C to attenuate liver regeneration in NK-depleted
      mice. Finally, administration of polyI:C or IFN-gamma enhances expression of
      several antiproliferative proteins, including STAT1, IRF-1, and p21cip1/waf1 in
      the livers of partially hepatectomized mice. CONCLUSIONS: Our findings suggest
      that viral infection and the TLR3 ligand negatively regulate liver regeneration
      via activation of innate immunity (NK/IFN-gamma), which may play an important
      role in the pathogenesis of viral hepatitis.

PMID- 15521019
TI  - Hepatitis C core and nonstructural 3 proteins trigger toll-like receptor 2
      mediated pathways and inflammatory activation.
AB  - BACKGROUND AND AIMS: Recent evidence suggests that toll-like receptors (TLRs)
      recognize certain viruses. We reported that hepatitis C virus (HCV) core and
      nonstructural 3 (NS3) proteins activate inflammatory pathways in monocytes. The
      aim of this study was to investigate the role of TLRs in innate immune cell
      activation by core and NS3 proteins. METHODS: Human monocytes, human embryonic
      kidney cells transfected with TLR2, and peritoneal macrophages from TLR2, MyD88
      knockout, and wild-type mice were studied to determine intracellular signaling
      and proinflammatory cytokine induction by HCV proteins. RESULTS: HCV core and NS3
      proteins triggered inflammatory cell activation via the pattern recognition
      receptor TLR2 and failed to activate macrophages from TLR2 or MyD88-deficient
      mice. HCV core and NS3 induced interleukin (IL)-1 receptor-associated kinase
      (IRAK) activity, phosphorylation of p38, extracellular regulated (ERK), and c-jun
      N-terminal (JNK) kinases and induced AP-1 activation. Activation of nuclear
      factor-kappaB by core and NS3 was associated with increased IkappaBalpha
      phosphorylation. TLR2-mediated cell activation was dependent on the conformation
      of core and NS3 proteins and required sequences in the regions of aa 2-122 in
      core and aa 1450-1643 in NS3. Although cellular uptake of core and NS3 proteins
      was independent of TLR2 expression, cell activation required TLR2. HCV core
      protein and TLR2 showed intracellular colocalization. The hyper-elevated TNF
      alpha induction by TLR2 ligands in monocytes of HCV-infected patients was not due
      to increased TLR2 expression. CONCLUSIONS: HCV core and NS3 proteins trigger
      inflammatory pathways via TLR2 that may affect viral recognition and contribute
      to activation of the innate immune system.

PMID- 15521021
TI  - Involvement of the Src family kinase yes in bile salt-induced apoptosis.
AB  - BACKGROUND AND AIMS: Hydrophobic bile acids induce CD95 (Fas, APO-1)-dependent
      hepatocyte apoptosis, which involves epidermal growth factor receptor (EGFR)
      catalyzed CD95 tyrosine phosphorylation. The mechanisms underlying bile salt
      induced EGFR activation remain unclear. METHODS: Bile acid-induced EGFR
      activation was studied in 24-hour cultured rat hepatocytes and perfused rat
      liver. RESULTS: The proapoptotic bile salts taurolithocholate-3-sulfate (TLCS),
      glycochenodesoxycholate (GCDC) and taurochenodeoxycholate (TCDC), but not
      taurocholate (TC), activate within 1 minute the Src kinase family member Yes,
      followed by an association of Yes with EGFR and subsequent EGFR activation. EGFR
      phosphorylation by TLCS involves tyrosines 845 and 1173 but not 1045. Yes/EGFR
      association and EGFR activation were sensitive to inhibition by SU6656 but not by
      PP-2. cAMP had no effect on TLCS and GCDC-induced Yes activation but induced
      Ser/Thr phosphorylation of Yes and prevented Yes/EGFR association and subsequent
      EGFR activation. Both SU6656 and cAMP had no effect on bile salt-induced c-Jun N
      terminal kinase activation, but blocked bile salt-induced CD95 tyrosine
      phosphorylation, membrane trafficking of CD95, formation of the death-inducing
      signaling complex, and apoptosis. In 4-day cultured hepatocytes, knockdown of
      either Yes or EGFR strongly attenuated bile salt-induced CD95 activation and
      apoptosis. CONCLUSIONS: The data identify the Src kinase Yes as an upstream
      target of proapoptotic bile acids, which triggers EGFR activation, subsequent
      CD95 tyrosine phosphorylation, and apoptosis. The antiapoptotic effect of cAMP
      involves a protein kinase A-dependent inhibition of Yes/EGFR association, thereby
      preventing EGFR activation, which is required for CD95 activation.

PMID- 15521022
TI  - Use of laboratory testing to guide 6-mercaptopurine/azathioprine therapy.

PMID- 15521023
TI  - The cholangiopathies: disorders of biliary epithelia.

PMID- 15521024
TI  - CpG island methylation in gastroenterologic neoplasia: a maturing field.
AB  - Fifteen years after the first demonstration of epigenetic tumor-suppressor gene
      inactivation associated with promoter methylation, the field has reached a level
      of understanding that threatens a re-writing of established biologic concepts. In
      gastrointestinal malignancies, epigenetic analysis has led to novel hypotheses
      regarding the etiology of age-associated cancer susceptibility and the
      interactions between environmental exposures and neoplasia. Methylation profiling
      has uncovered a distinct pathway to colorectal neoplasia that may arise from a
      hitherto underestimated precursor lesion, the proximal hyperplastic polyp
      serrated adenoma pathway. Epigenetic information has shown promise in clarifying
      susceptibility to cancer and defining poor prognosis groups in gastrointestinal
      cancers. Finally, the field has engendered renewed interest in therapeutic
      targeting of epigenetic regulatory molecules, and several such drugs are
      currently in clinical trials. It is likely that epigenetic pathways will be
      integrated in the routine management of gastrointestinal malignancies over the
      next decade.

PMID- 15521025
TI  - American Gastroenterological Association medical position statement: diagnosis
      and treatment of gastroparesis.
AB  - This document presents the official recommendations of the American
      Gastroenterological Association (AGA) on Diagnosis and Treatment of
      Gastroparesis. It was approved by the Clinical Practice Committee on May 16,
      2004, and by the AGA Governing Board on September 23, 2004.

PMID- 15521026
TI  - American Gastroenterological Association technical review on the diagnosis and
      treatment of gastroparesis.
AB  - This literature review and the recommendations herein were prepared for the
      American Gastroenterological Association Clinical Practice Committee. The paper
      was approved by the Committee on May 16, 2004, and by the AGA Governing Board on
      September 23, 2004.

PMID- 15521027
TI  - CT colonography: progress toward colorectal evaluation without catharsis.

PMID- 15521028
TI  - Cooling the patient with acute liver failure.

PMID- 15521029
TI  - Hepatitis C: it's a long way to new therapy, it's a long way to go...

PMID- 15521030
TI  - Virtual colonoscopy: good results and not so good results -- why the difference?

PMID- 15521032
TI  - Improving prognosis in pancreatic cancer-an uphill endeavor.

PMID- 15521033
TI  - Anti-TNF therapy for severe acute alcoholic hepatitis: what went wrong?

PMID- 15521034
TI  - The spice of life for cystic fibrosis.

PMID- 15521039
TI  - The treatment of incidental esophageal varices.

PMID- 15521041
TI  - Primary biliary cirrhosis in genetically identical twins.

PMID- 15521043
TI  - Use of fecal lactoferrin to diagnose irritable pouch syndrome: a word of caution.

PMID- 15521044
TI  - Back pain and irritable bowel syndrome.

PMID- 15521046
TI  - Are adherent Escherichia coli in Crohn's disease and colon cancer truly
      pathogenic?

PMID- 15521050
TI  - Gene transfer of constitutively active caspase-3 induces apoptosis in a human
      hepatoma cell line.
AB  - BACKGROUND: The caspase-3 gene is expressed at significantly lower levels in
      human hepatocellular carcinomas than in normal hepatocytes. Gene transfer
      technologies offer the possibility to restore caspase-3 gene expression. We
      explored the interest for cancer gene therapy of a constitutively active
      recombinant caspase-3 (RevCasp3) obtained by rearranging its subunits. METHODS:
      An amphotropic retroviral vector was used to express the RevCasp3 gene. HuH7
      cells were infected 1 and 2 days after plating. Caspase-3 activity was measured
      every 24 h for the following 6 days. The level of poly (ADP-ribose) polymerase
      cleavage induced by caspase-3 was measured by Western blot. The percentage of
      apoptotic cells was estimated after Hoechst-acridine orange and TUNEL stainings.
      RESULTS: Caspase-3 activity significantly increased from days 4 to 7 after
      infection. Caspase-3 activity peaked on day 7, and was 5.4-fold higher in
      RevCasp3-transduced HuH7 cells than in control cells. Poly (ADP-ribose)
      polymerase cleavage was first detected 6 days after the first infection. Hoechst
      acridine orange and TUNEL stainings showed that most infected HuH7 cells were
      apoptotic. CONCLUSIONS: Apoptosis was selectively induced following infection of
      HuH7 cells with RevCasp3, demonstrating that retroviruses expressing RevCasp3 are
      of potential interest for the treatment of hepatocellular carcinomas and other
      tumour types.

PMID- 15521051
TI  - Regulatory sequences of H19 and IGF2 genes in DNA-based therapy of colorectal rat
      liver metastases.
AB  - BACKGROUND: Malignant tumors of the liver are among the most common causes of
      cancer-related death throughout the world. Current therapeutic approaches fail to
      control the disease in most cases. This study seeks to explore the potential
      utility of transcriptional regulatory sequences of the H19 and insulin growth
      factor 2 (IGF2) genes for directing tumor-selective expression of a toxin gene (A
      fragment of diphtheria toxin), delivered by non-viral vectors. METHODS: The
      therapeutic potential of the toxin vectors driven by the H19 and the IGF2-P3
      regulatory sequences was tested in a metastatic model of rat CC531 colon
      carcinoma in liver. RESULTS: Intratumoral injection of these vectors into colon
      tumors implanted in the liver of rats induced an 88% and a 50% decrease
      respectively in the median tumor volume as compared with the control groups. This
      therapeutic action was accompanied by increased necrosis of the tumor.
      Importantly, no signs of toxicity were detected in healthy animals after their
      treatment by the toxin expression vectors. CONCLUSIONS: DT-A was preferentially
      expressed in liver metastases after being transfected with H19 or IGF2-P3
      promoter-driven DT-A expression plasmids, causing a very significant inhibition
      of tumor growth as a result of its cytotoxic effect. Our findings strongly
      support the feasibility of our proposed therapeutic strategy, which may
      contribute to open new gene therapeutic options for human liver metastases.

PMID- 15521053
TI  - Increased SFHR gene correction efficiency with sense single-stranded DNA.
AB  - BACKGROUND: The correction of a mutated gene by the small fragment homologous
      replacement (SFHR) method is a highly attractive approach for gene therapy.
      However, the current SFHR method with a heat-denatured double-stranded PCR
      fragment yielded a low correction efficiency. METHODS: Single-stranded (ss) DNA
      fragments were prepared from ss phagemid DNA and tested in a gene correction
      assay with an inactivated Hyg-EGFP fusion gene, as a model target. RESULTS: A 606
      nt sense, ss DNA fragment dramatically (12-fold) improved the gene correction
      efficiency, although the antisense strand showed only minimal correction
      efficiency. CONCLUSIONS: These results suggest that the use of a sense, single
      stranded DNA fragment is useful in the SFHR method for the correction of mutated
      genes.

PMID- 15521052
TI  - Complement inhibition rescued mice allowing observation of transgene expression
      following intraportal delivery of baculovirus in mice.
AB  - BACKGROUND: The baculovirus Autographa californica nucleo-polyhedrosis virus
      (AcNPV) is an alternative to other viral vectors for hepatic gene delivery. A
      barrier to AcNPV being used in vivo is its susceptibility to inactivation by
      serum complement 1. In vivo utility has only been demonstrated using methods that
      avoid contact with serum 2-5. We have studied the complement pathways involved in
      baculovirus inactivation in vitro and the systemic administration of baculovirus
      vectors in vivo, with the co-administration of the complement inhibitor, soluble
      complement inhibitor 1 (sCR1). RESULTS: EDTA increased baculovirus survival in
      human serum more than EGTA showing that both the alternative and classical
      pathways of complement are activated. Depleting serum of IgM increased survival,
      whereas reconstitution with pooled IgM restored activity against baculovirus,
      suggesting naturally occurring IgM antibodies with affinity for baculovirus may
      be partially responsible for complement activation. Intraportal administration of
      baculovirus led to hepatic expression when the complement inhibitor sCR1 (soluble
      complement receptor type 1) was co-administered by tail vein injection; however,
      liver histology showed hepatic necrosis. Without co-administration of sCR1,
      intraportal infusion of baculovirus was fatal within 24 h. Histology demonstrated
      massive hepatic necrosis. Yolk sac vein injection of baculovirus was associated
      with fetal death. CONCLUSIONS: Transgene expression was demonstrated following
      intraportal infusion of recombinant baculovirus vectors in combination with sCR1;
      however, our experiments suggest a significant associated toxicity.

PMID- 15521054
TI  - Self-assembly of the octanuclear cluster [Cu8(OH)10(NH2(CH2)2CH3)12]6+ and the
      one-dimensional N-propylcarbamate-linked coordination polymer
      {[Cu(O2CNH(CH2)2CH3)(NH2(CH2)2CH3)3](ClO4)}n.
AB  - The reaction of Cu(ClO4)2.6-H2O and n-propylamine in methanol gives two high
      nuclearity products of well-defined compositions. At amine concentrations greater
      than seven equivalents compared to copper ion concentration, the system fixes
      carbon dioxide from air to form the one-dimensional carbamate-bridged
      coordination polymer, {[Cu(mu2-O,O'-O2CNH(CH2)2CH3)(NH2(CH2)2CH3)3](ClO4)}n ({1
      ClO4}n). Lower relative amine concentrations lead to the self-assembly of an
      octanuclear copper-amine-hydroxide cluster [Cu8(OH)10(NH2(CH2)2CH3)12]6+ (2).
      Both compounds exhibit unique structures: {1-ClO4}n is the first mu2-O,O'-mono-N
      alkylcarbamate-linked coordination polymer and 2 is the largest copper-hydroxide
      monodentate amine cluster identified to date. The crystal structures indicate
      that the size of the n-propyl group is probably crucial for directing the
      formation of these compounds. Magnetic susceptibility studies indicate very weak
      antiferromagnetic coupling for 1. The octanuclear cluster 2 displays slightly
      stronger net antiferromagnetic coupling, despite the presence of a number of Cu
      O(H)-Cu angles below the value of about 97 degrees that would normally be
      expected to yield ferromagnetic coupling.

PMID- 15521055
TI  - Intramolecular gamma-hydroxylations of nonactivated C-H bonds with copper
      complexes and molecular oxygen.
AB  - Copper(I) complexes incorporating the isomeric bidentate ligands IMPY
      (iminomethyl-2-pyridines) or AMPY (aminomethylene-2-pyridines) are quite unusual
      in their ability to bind and activate molecular oxygen. Using these complexes,
      hydroxylations of nonactivated CH, CH2, or CH3 groups in the gamma-position in
      relation to the imino-nitrogen atom, and with a specific orientation of one H
      atom with respect to the binuclear Cu-O species, can be achieved in synthetically
      useful yields. Through mechanistic studies employing conformationally well
      defined molecules (for example, cyclic isoprenoids), coupled with solid-state X
      ray structure analyses and force-field calculations, we postulate a seven
      membered transition state for this reaction in which six atoms lie approximately
      in a plane. This plane is defined by the positions of the lone pairs on the
      nitrogen atoms, as well as the copper and the oxygen atoms. For a successful
      hydroxylation, one hydrogen atom should be located close to this plane.
      Prediction of the stereochemical course of these reactions is possible based on a
      simple geometrical criterion. The convenient introduction of IMPY and AMPY groups
      as auxiliaries into oxo and primary amino compounds and the simple hydrolysis
      after the hydroxylation procedure has allowed the synthesis of 3-hydroxy-1-oxo
      and 3-hydroxy-1-amino compounds. If desired, the 3-hydroxy-1-IMPY and -1-AMPY
      compounds can be reduced with NaBH4 to obtain 3-hydroxy-1-aminomethylpyridines.
      For a successful hydroxylation procedure, the method employed for the synthesis
      of the CuI complexes is very important. Starting either from CuI salts or from
      CuII salts with a subsequent reduction with benzoin/triethylamine may turn out to
      be the better way, depending on the ligand and the molecular structure.

PMID- 15521057
TI  - Energy landscape of a small peptide revealed by dihedral angle principal
      component analysis.
AB  - A 100 ns molecular dynamics simulation of penta-alanine in explicit water is
      performed to study the reversible folding and unfolding of the peptide. Employing
      a standard principal component analysis (PCA) using Cartesian coordinates, the
      resulting free-energy landscape is found to have a single minimum, thus
      suggesting a simple, relatively smooth free-energy landscape. Introducing a novel
      PCA based on a transformation of the peptide dihedral angles, it is found,
      however, that there are numerous free energy minima of comparable energy (less
      than or approximately 1 kcal/mol), which correspond to well-defined structures
      with characteristic hydrogen-bonding patterns. That is, the true free-energy
      landscape is actually quite rugged and its smooth appearance in the Cartesian PCA
      represents an artifact of the mixing of internal and overall motion. Well
      separated minima corresponding to specific conformational structures are also
      found in the unfolded part of the free energy landscape, revealing that the
      unfolded state of penta-alanine is structured rather than random. Performing a
      connectivity analysis, it is shown that neighboring states are connected by low
      barriers of similar height and that each state typically makes transitions to
      three or four neighbor states. Several principal pathways for helix nucleation
      are identified and discussed in some detail.

PMID- 15521056
TI  - Risk and protective factors for Parkinson's disease: a study in Swedish twins.
AB  - Many studies have shown a protective effect of cigarette smoking on Parkinson's
      disease. However, criticism has been raised concerning confounding by genetic
      factors. We investigated the associations between Parkinson's disease and
      smoking, alcohol, coffee, area of living, and education in a co-twin control
      study. Because twins are matched for genetic and familial environmental factors,
      this design controls for confounding by these factors. We also examined control
      subjects unrelated to cases. Exposure information was taken from questionnaires
      answered in the 1960s and 1970s. Parkinson's disease cases were identified
      through the Swedish Inpatient Discharge Register (IDR) and the Cause of Death
      Register. In the unrelated control subject comparison, 476 Parkinson's disease
      cases and 2,380 control subjects were included. In the co-twin control
      comparison, 415 same-sex twin pairs were included. There was an inverse
      association between smoking and Parkinson's disease using unrelated control
      subjects and co-twin control cases. There was no association between Parkinson's
      disease and alcohol, coffee, or area of living. High educational level was
      associated with Parkinson's disease in the unrelated control subject comparison
      but not in the co-twin control comparison. We confirm the protective effect of
      smoking on Parkinson's disease and establish that the association is only
      partially explained by genetic and familial environmental factors.

PMID- 15521058
TI  - Associative mechanism for phosphoryl transfer: a molecular dynamics simulation of
      Escherichia coli adenylate kinase complexed with its substrates.
AB  - The ternary complex of Escherichia coli adenylate kinase (ECAK) with its
      substrates adenosine monophosphate (AMP) and Mg-ATP, which catalyzes the
      reversible transfer of a phosphoryl group between adenosine triphosphate (ATP)
      and AMP, was studied using molecular dynamics. The starting structure for the
      simulation was assembled from the crystal structures of ECAK complexed with the
      bisubstrate analog diadenosine pentaphosphate (AP(5)A) and of Bacillus
      stearothermophilus adenylate kinase complexed with AP(5)A, Mg(2+), and 4
      coordinated water molecules, and by deleting 1 phosphate group from AP(5)A. The
      interactions of ECAK residues with the various moieties of ATP and AMP were
      compared to those inferred from NMR, X-ray crystallography, site-directed
      mutagenesis, and enzyme kinetic studies. The simulation supports the hypothesis
      that hydrogen bonds between AMP's adenine and the protein are at the origin of
      the high nucleoside monophosphate (NMP) specificity of AK. The ATP adenine and
      ribose moieties are only loosely bound to the protein, while the ATP phosphates
      are strongly bound to surrounding residues. The coordination sphere of Mg(2+),
      consisting of 4 waters and oxygens of the ATP beta- and gamma-phosphates, stays
      approximately octahedral during the simulation. The important role of the
      conserved Lys13 in the P loop in stabilizing the active site by bridging the ATP
      and AMP phosphates is evident. The influence of Mg(2+), of its coordination
      waters, and of surrounding charged residues in maintaining the geometry and
      distances of the AMP alpha-phosphate and ATP beta- and gamma-phosphates is
      sufficient to support an associative reaction mechanism for phosphoryl transfer.

PMID- 15521059
TI  - Study of the Villin headpiece folding dynamics by combining coarse-grained Monte
      Carlo evolution and all-atom molecular dynamics.
AB  - The folding mechanism of the Villin headpiece (HP36) is studied by means of a
      novel approach which entails an initial coarse-grained Monte Carlo (MC) scheme
      followed by all-atom molecular dynamics (MD) simulations in explicit solvent. The
      MC evolution occurs in a simplified free-energy landscape and allows an efficient
      selection of marginally-compact structures which are taken as viable initial
      conformations for the MD. The coarse-grained MC structural representation is
      connected to the one with atomic resolution through a "fine-graining"
      reconstruction algorithm. This two-stage strategy is used to select and follow
      the dynamics of seven different unrelated conformations of HP36. In a notable
      case the MD trajectory rapidly evolves towards the folded state, yielding a
      typical root-mean-square deviation (RMSD) of the core region of only 2.4 A from
      the closest NMR model (the typical RMSD over the whole structure being 4.0 A).
      The analysis of the various MC-MD trajectories provides valuable insight into the
      details of the folding and mis-folding mechanisms and particularly about the
      delicate influence of local and nonlocal interactions in steering the folding
      process.

PMID- 15521060
TI  - Chronic nicotine and smoke treatment modulate dopaminergic activities in ventral
      tegmental area and nucleus accumbens and the gamma-aminobutyric acid type B
      receptor expression of the rat prefrontal cortex.
AB  - Dopaminergic afferents from the mesencephalic areas, such as ventral tegmental
      area (VTA), synapse with the gamma-aminobutyric acid (GABA)-ergic interneurons in
      the prefrontal cortex (PFC). Pharmacological and electrophysiological data show
      that the reinforcement, the dependence-producing properties, as well as the
      psychopharmacologic effects of nicotine depend to a great extent on activation of
      nicotinic receptors within the mesolimbocortical dopaminergic projection. To
      explore further the relationship between the mesencephalic dopaminergic neurons
      and PFC GABAergic neurons, we investigated the effects of nicotine and passive
      exposure to cigarette smoke on the regulation of tyrosine hydroxylase (TH) in VTA
      and substantia nigra (SNC) and dopamine (DA) D1 receptor levels in nucleus
      accumbens (NAc) and caudate-putamen (CPu). Also, the simultaneous changes in
      GABAB receptors mRNAs in the PFC were studied. The results showed that chronic
      nicotine and smoking treatment differentially changed the levels of TH protein in
      VTA and SNC and DA D1 receptor levels in Nac and CPu. GABAB1 and GABAB2 receptor
      mRNA levels also showed different change patterns. Ten and thirty minutes of
      smoke exposure increased GABAB1 receptor mRNA to a greater extent than that of
      GABAB2, whereas GABAB2 was greatly enhanced after 1 hr of smoke exposure. The TH
      levels in VTA were closely related to DA D1 receptor levels in NAc and with GABAB
      receptor mRNA changes in PFC. These results suggest that the mesolimbic pathway
      and GABAB receptor mRNA in PFC are modulated by nicotine and cigarette smoke,
      implying an important role in nicotine's psychopharmacological effects.

PMID- 15521061
TI  - In vivo optical imaging of tone-evoked activity in the dorsal cochlear nucleus
      with a voltage sensitive dye.
AB  - We investigated the use of optical imaging for observing the spatial patterns of
      neural activation in the dorsal cochlear nucleus (DCN) of hamsters during tonal
      stimulation. The patterns of activation were studied in the DCN, in vivo,
      following application of a voltage sensitive dye, Di-2-ANEPEQ, to the DCN
      surface. Beginning 60-90 min following dye application, tones were presented to
      the ipsilateral ear. Electrophysiological recordings after dye application
      revealed no significant toxicity of Di-2-ANEPEQ that affected the frequency
      tuning properties of DCN neurons. We examined areas of activation in response to
      each of a series of test stimuli consisting of pure tones ranging in frequency
      from 2 to 20 kHz. For each stimulus condition, images were collected over a
      stimulus interval of 400 msec and averaged over 32 stimulus repetitions. These
      images revealed areas of activation with definable epicenters. The epicenters
      shifted from lateral to more medial locations on the DCN surface with increases
      in stimulus frequency. Comparison with electrophysiological data indicated a
      close parallel between the tonotopic gradient defined by optical imaging and that
      defined by the distribution of characteristic frequencies. The principal temporal
      and spatial features of these optical responses are described.

PMID- 15521062
TI  - Solvation influences flap collapse in HIV-1 protease.
AB  - HIV-1 protease (HIVp) is an important target for the development of therapies to
      treat AIDS and is one of the classic examples of structure-based drug design. The
      flap region of HIVp is known to be highly flexible and undergoes a large
      conformational change upon binding a ligand. Accurately modeling the inherent
      flexibility of the HIVp system is critical for developing new methods for
      structure-based drug design. We report several 3-ns molecular dynamics
      simulations investigating the role of solvation in HIVp flap rearrangement. Using
      an unliganded crystal structure of HIVp, other groups have observed flap
      reorganization on the nanosecond timescale. We have also observed rapid, initial
      flap movement, but we propose that it may be caused by system setup. The initial
      solvation of the system creates vacuum regions around the protein that may
      encourage large conformational deformities. By reducing the vacuum space created
      by the solvation routine, the observed flap collapse is attenuated. Also, a more
      thorough equilibration procedure preserves a more stable protein conformation
      over the course of the simulation.

PMID- 15521063
TI  - 5-HT1A receptors modulate small-conductance Ca2+-activated K+ channels.
AB  - Small-conductance calcium-activated potassium channels (SK) are responsible for
      the medium afterhyperpolarisation (mAHP) following action potentials in neurons.
      Here we tested the ability of serotonin (5-HT) to modulate the activity of SK
      channels by coexpressing 5-HT1A receptors with different subtypes of SK channels
      (SK1, SK2, and SK3) in Xenopus laevis oocytes. SK channels were activated by
      intracellular injection of Cd2+. Subsequent activation of 5-HT1A receptors by 8
      OH-DPAT always produced an inhibition of the SK current, showing the existence of
      a specific pathway between the receptor and the ion channel. To investigate the
      physiological relevance of this pathway, we characterized the mAHP present after
      action potentials in spinal motoneurons recorded in a slice preparation from the
      lumbar spinal cord of the adult turtle. By performing current and voltage clamp
      recordings, we showed that 8-OH-DPAT specifically inhibited the fraction of the
      AHP mediated by SK channels. We conclude that the activity of SK channels is
      modulated by activation of serotonergic receptors.

PMID- 15521064
TI  - FGF-2 enhances the mitotic and chondrogenic potentials of human adult bone marrow
      derived mesenchymal stem cells.
AB  - Human mesenchymal stem cells (hMSCs) expanded with and without fibroblast growth
      factor (FGF) supplementation were compared with respect to their proliferation
      rate, ability to differentiate along the chondrogenic pathway in vitro, and their
      gene expression profiles. hMSCs expanded in FGF-supplemented medium were smaller
      and proliferated more rapidly than hMSCs expanded in control conditions.
      Chondrogenic cultures made with FGF-treated cells were larger and contain more
      proteoglycan than those made with control cells. Furthermore, aggregates of FGF
      treated cells lacked the collagen type I-positive and collagen type II-negative
      outer layer characteristic of aggregates of control cells. A total of 358 unique
      transcripts were differentially expressed in FGF-treated hMSCs. Of these, 150
      were upregulated and 208 downregulated. Seventeen percent of these genes affect
      proliferation. Known genes associated with cellular signaling functions comprised
      the largest percentage ( approximately 20%) of differentially expressed
      transcripts. Eighty percent of differentially expressed extracellular matrix
      related genes were downregulated. The present findings that FGF-2 enhances
      proliferation and differentiation of hMSCs adds to a growing body of evidence
      that cytokines modulate the differentiation potential and, perhaps, the
      multipotentiality of adult stem cells. With the generation of gene expression
      profiles of FGF-treated and control cells we have taken the first steps in the
      elucidation of the molecular mechanism(s) behind these phenomena.

PMID- 15521065
TI  - Noonan syndrome type I with PTPN11 3 bp deletion: structure-function
      implications.
AB  - Noonan syndrome was recently reported to be caused by mutations in the PTPN11
      gene in 40% of the cases. This gene encodes the nonreceptor-type protein tyrosine
      phosphatase SHP-2 and has been shown to be self down-regulated with the
      concurrency of two SH2 domains. Insertion of a specific loop (D'EF) from N
      terminal SH2 domain into the SHP-2 active-site is responsible for the reversible
      inhibition of the phosphatase activity. Here we report the first in frame
      trinucleotide deletion resulting in the removal of Aspartate 61 (D61del), a key
      residue of the N-terminal SH2 D'EF loop. Energetic-based structural analysis and
      electrostatic calculations carried out on the wild-type and mutant proteins
      predict lower stability of the D'EF loop for the D61del variant as compared to
      the wild type indicating better access to the active site and most likely an
      enzyme activated for longer extent. Similar computations were performed on the
      previously functionally characterized gain-of-function D61Y mutant and similar
      behaviors were observed. The simulation data for the D61del and D61Y mutants
      suggest that both variants could yield more catalytic cycles than the wild-type
      molecule in the same timespan because of the opening of the active site. It also
      supports the notion that D61 plays a major role for proper down-regulation of the
      protein tyrosine phosphatase activity of SHP-2.

PMID- 15521066
TI  - Expression of the urokinase receptor regulates focal adhesion assembly and cell
      migration in adenoid cystic carcinoma cells.
AB  - Adenoid cystic carcinoma (AdCC) cell lines (ACCS and ACCT) showed higher
      migration responses and adhesion to the extracellular matrix (ECM), especially
      types I and IV collagen, than did the oral squamous cell carcinoma (SCC) lines
      (NA and TF). The response to collagens was largely and exclusively inhibited by
      anti-alpha(2) integrin antibody. Moreover, AdCC cell lines expressed higher
      surface levels of urokinase-type plasminogen activator receptor (uPAR) than did
      SCC cell lines. When AdCC cells were plated on collagen, the surface level of
      uPAR was increased, and numerous focal adhesions consisting of uPAR, vinculin,
      and paxillin were assembled; whereas collagen-stimulated SCC cell counterparts or
      AdCC cells plated on other types of ECM, such as fibronectin, failed to assemble
      such definite focal adhesions. In order to elucidate the association of uPAR with
      collagen-induced events, an ACCS-AS cell line transfected with a vector
      expressing antisense uPAR RNA was established and shown to have reduced uPAR
      (about 10% that of parental ACCS at both the protein and mRNA levels). ACCS-AS
      showed a strong reduction of collagen-stimulated migration and focal adhesion
      assembly of alpha(2) integrin, vinculin, and paxillin. These findings suggest
      that AdCC has a proclivity for migrating to types I and IV collagens due to the
      overexpression of uPAR, which plays a key role in focal adhesion assembly and
      migration.

PMID- 15521067
TI  - Cholesterol depletion perturbs calcium handling by rat submandibular glands.
AB  - The sensitivity to cholesterol depletion of calcium handling by rat submandibular
      glands was investigated. The glands were digested with collagenase. After
      homogenization, the lysate was extracted at 4 degrees C with 0.5% Triton X-100
      and the extract was submitted to an ultracentrifugation in a sucrose
      discontinuous gradient. A population of detergent-resistant membranes (DRM) was
      collected at the 5%-35% interface. The DRM had a higher content of cholesterol,
      saturated and long-chain fatty acids. Caveolin-1 and alpha(q/11) were located in
      these membranes. They were more ordered than vesicles from total cellular lysate
      as determined by anisotropy measurement. They disappeared after cholesterol
      extraction with methyl-beta-cyclodextrin (MCD). Exposure of the cellular
      suspension with MCD nearly abolished the response to carbachol, epinephrine, and
      substance P and inhibited the activation of phospholipase C (PLC) by these
      agonists and by sodium fluoride. MCD did not affect the mobilization of
      intracellular pools of calcium by thapsigargin. It increased the uptake of
      extracellular calcium or barium and did not inhibit the uptake of calcium after
      depletion of the intracellular stores of this ion. From these results, it is
      concluded that Triton X-100 can extract a fraction of membrane resistant to
      detergents. Treatment of the cells with MCD disrupts these membranes. The
      coupling between the heterotrimeric GTP-binding protein G(q/11) and poly
      phosphoinositide-specific PLC is affected by disruption of these membrane
      fractions. At the opposite, the store-operated calcium channel (SOCC) is not
      affected by DRM-disruption.

PMID- 15521068
TI  - Hedgehog signaling in normal urothelial cells and in urothelial carcinoma cell
      lines.
AB  - Constitutive activation of hedgehog signaling, often caused by PTCH1 inactivation
      and leading to inappropriate activation of GLI target genes, is crucial for the
      development of several human tumors including basal cell carcinoma of the skin
      and medulloblastoma. The PTCH1 gene at 9q22 is also considered as a candidate
      tumor suppressor in transitional cell carcinoma (TCC), of which >50% show LOH in
      this region. However, only rare mutations have been found in PTCH1. We have
      therefore investigated GLI-dependent promoter activity and expression of hedgehog
      pathway components in TCC cell lines and proliferating normal urothelial cells.
      Normal urothelial cells cultured in serum-free medium, but not TCC lines
      exhibited low, but significant promoter activity under standard growth
      conditions. Accordingly, GLI1-3 and PTCH1 mRNAs were expressed at moderate
      levels, and sonic hedgehog (SHH) mRNA expression was low to undetectable. In co
      transfection experiments GLI1 increased promoter activity significantly in one
      TCC line and further in normal urothelial cells, but less strongly in other TCC
      lines. Expression patterns of GLI factor mRNAs did not correlate with
      inducibility. No significant effects of SHH or cyclopamine on proliferation were
      observed, ruling out autocrine effects. However, SHH induced GLI-dependent
      promoter activity in normal urothelial cells. Taken together, our data suggest
      that the hedgehog pathway is weakly active in normal adult urothelial cells and
      of limited importance in TCC.

PMID- 15521069
TI  - Mitochondrial tissue specificity of substrates utilization in rat cardiac and
      skeletal muscles.
AB  - As energetic metabolism is crucial for muscles, they develop different
      adaptations to respond to fluctuating demand among muscle types. Whereas
      quantitative characteristics are known, no study described simultaneously
      quantitative and qualitative differences among muscle types in terms of
      substrates utilization patterns. This study thus defined the pattern of
      substrates preferential utilization by mitochondria from glycolytic gastrocnemius
      (GAS) and oxidative soleus (SOL) skeletal muscles and from heart left ventrical
      (LV) in rats. We measured in situ, ADP (2 mM)-stimulated, mitochondrial
      respiration rates from skinned fibers in presence of increasing concentrations of
      pyruvate (Pyr) + malate (Mal), palmitoyl-carnitine (Palm-C) + Mal, glutamate
      (Glut) + Mal, glycerol-3-phosphate (G3-P), lactate (Lact) + Mal. Because the
      fibers oxygen uptake (Vs) followed Michaelis-Menten kinetics in function of
      substrates level we determined the Vs and Km, representing maximal oxidative
      capacity and the mitochondrial sensibility for each substrate, respectively. Vs
      were in the order GAS < SOL < LV for Pyr, Glu, and Palm-C substrates, whereas in
      the order SOL = LV < GAS with G3-P. Moreover, the relative capacity to oxidize
      Palm-C is extremely higher in LV than in SOL. Vs was not stimulated by the Lact
      substrate. The Km was equal for Pyr among muscles, but much lower for G3-P in GAS
      and lower for Palm-C in LV. These results demonstrate qualitative mitochondrial
      tissue specificity for metabolic pathways. Mitochondria of glycolytic muscle
      fibers are well adapted to play a central role for maintaining a satisfactory
      cytosolic redox state in these fibers, whereas mitochondria of LV developed
      important capacities to use fatty acids.

PMID- 15521070
TI  - The role of caldesmon in the regulation of endothelial cytoskeleton and
      migration.
AB  - The actin- and myosin-binding protein, caldesmon (CaD) is an essential component
      of the cytoskeleton in smooth muscle and non-muscle cells and is involved in the
      regulation of cell contractility, division, and assembly of actin filaments. CaD
      is abundantly present in endothelial cells (EC); however, the contribution of CaD
      in endothelial cytoskeletal arrangement is unclear. To examine this contribution,
      we generated expression constructs of l-CaD cloned from bovine endothelium. Wild
      type CaD (WT-CaD) and truncated mutants lacking either the N-terminal myosin
      binding site or the C-terminal domain 4b (containing actin- and calmodulin
      binding sites) were transfected into human pulmonary artery EC. Cell
      fractionation experiments and an actin overlay assay demonstrated that deleting
      domain 4b, but not the N-terminal myosin-binding site, resulted in decreased
      affinity to both the detergent-insoluble cytoskeleton and soluble actin.
      Recombinant WT-CaD co-localized with acto-myosin filaments in vivo, but neither
      of CaD mutants did. Thus both domain 4b and the myosin-binding site are essential
      for proper localization of CaD in EC. Overexpression of WT-CaD led to cell
      rounding and formation of a thick peripheral subcortical actin rim in quiescent
      EC, which correlated with decreased cellular migration. Pharmacological
      inhibition of p38 MAPK, but not ERK MAPK, caused disassembly of this peripheral
      actin rim in CaD-transfected cells and decreased CaD phosphorylation at Ser531
      (Ser789 in human h-CaD). These results suggest that CaD is critically involved in
      the regulation of the actin cytoskeleton and migration in EC, and that p38 MAPK
      mediated CaD phosphorylation may be involved in endothelial cytoskeletal
      remodeling.

PMID- 15521071
TI  - Selective reduction of fibrotic markers in repairing corneas of mice deficient in
      Smad3.
AB  - The cytokine transforming growth factor-beta (TGF-beta) is a key mediator of
      fibrosis in all organs. Expression of fibrotic markers in repairing cutaneous
      wounds is reduced in mice lacking Smad3, a downstream cytoplasmic mediator of TGF
      beta signaling (Ashcroft et al., 1999, Nat Cell Biol 1(5):260-266). This is
      correlated with a reduction in inflammation, and thus in the blood elements
      thought to be a significant source of TGF-beta at the wound site, the principle
      form being TGF-beta1. Since the major cellular source of TGF-beta in corneal
      wounds is the epithelium, and the principal isoform is TGF-beta2, we investigated
      whether Smad3 deficiency has similar anti-fibrotic effects on corneal repair. In
      contrast to the situation of cutaneous repair, expression of the fibrotic marker,
      fibronectin, was equivalent in corneal repair tissue of Smad3-/- mice as compared
      to their +/- littermates, even though expression of a second fibrotic marker not
      previously examined in cutaneous wounds, alpha-smooth muscle (sm) actin, was
      reduced. Also unlike in cutaneous wounds, the inflammatory response was
      unaffected. These differences between corneal and cutaneous repair correlated
      with the lack of apparent change in the levels of corneal TGF-beta2. There was a
      significant reduction of alpha-sm actin expression in stromal cell cultures
      established from Smad3-/- mice as compared to their +/- littermates, but the rate
      of cell proliferation stimulated by TGF-beta, as well as expression of
      fibronectin, was unaffected. Therefore, a deficiency in Smad3 has different
      effects on corneal and cutaneous repair, probably due to the difference in
      cellular source and principal isoform of the TGF-beta involved.

PMID- 15521072
TI  - HSG cells differentiated by culture on extracellular matrix involves induction of
      S-adenosylmethione decarboxylase and ornithine decarboxylase.
AB  - The human salivary gland (HSG) epithelial cell line can differentiate when
      cultured on extracellular matrix preparations. We previously identified >30 genes
      upregulated by adhesion of HSG cells to extracellular matrix. In the current
      studies, we examined the role of one of these genes, the polyamine pathway
      biosynthetic enzyme S-adenosylmethionine decarboxylase (SAM-DC) and the related
      enzyme, ornithine decarboxylase (ODC), on HSG cell differentiation during culture
      on extracellular matrix. HSG cells cultured on fibronectin-, collagen I gel-, and
      Matrigel-coated substrates for 12-24 h upregulated SAM-DC and ODC mRNA expression
      and enzyme activity compared to cells cultured on non-precoated substrates. After
      3-5 days, HSG cells grown on Matrigel- or collagen I gel-coated substrates
      acquired a differentiated phenotype: the cells showed changes in culture
      morphology and increased expression of salivary gland differentiation markers
      (vimentin, SN-cystatin, and alpha-amylase). Further, culturing the cells on
      substrates precoated with an anti-beta1-integrin-antibody promoted
      differentiation-like changes. HSG cells cultured on collagen I- or Matrigel
      coated substrates rapidly entered the cell cycle but showed decreased cell
      proliferation at longer times. In contrast, cell proliferation was enhanced on
      fibronectin-coated substrates compared to cells on non-precoated substrates.
      Treatment with the polyamine synthesis inhibitors, difluoromethylornithine
      (DFMO), and methylglyoxal bis-(guanylhydrazone) (MGBG), inhibited cell
      proliferation and delayed (3)H-thymidine incorporation in HSG cells cultured on
      all of the substrates. Further, inclusion of DFMO and MGBG inhibited or delayed
      acquisition of the differentiated phenotype in HSG cells cultured on Matrigel- or
      collagen I gel-coated substrates. This suggests that the adhesion-dependent
      expression of SAM-DC and ODC contributes to extracellular matrix-dependent HSG
      cell differentiation.

PMID- 15521073
TI  - Transcriptional regulation of thioredoxin reductase 1 expression by cadmium in
      vascular endothelial cells: role of NF-E2-related factor-2.
AB  - Thioredoxin reductase (TrxR) is a selenoprotein that catalyzes the reduction of
      the active site disulfide of thioredoxin (Trx), which regulates the redox status
      of the cells. In the present study, we found that TrxR1, one of the three TrxR
      isozymes, was induced by cadmium as well as tumor necrosis factor alpha
      (TNFalpha) in bovine arterial endothelial cells (BAEC), and investigated the
      mechanism of cadmium-induced TrxR1 expression. We here showed that cadmium,
      differently from TNFalpha, enhanced the promoter activity of the 5'-flanking
      region of human TrxR1 gene (nucleotides -1692 to +49). Deletion and site-directed
      mutation of antioxidant responsive element (ARE) (nucleotides -62 to -48) in this
      region abolished the response to cadmium. Overexpression of NF-E2-related factor
      2 (Nrf2) augmented the TrxR1 promoter activity. In contrast, overexpression of
      the dominant negative mutant of Nrf2 suppressed cadmium-induced activation of
      TrxR1 promoter through the ARE. Chromatin immunoprecipitation (ChIP) assays
      showed that anti-Nrf2 antibody precipitated ARE from the chromatin of the cadmium
      treated cells. These results indicated that cadmium-induced TrxR1 gene expression
      is mediated by the activation of Nrf2 transcription factor and its binding to ARE
      in the TrxR1 gene promoter. We further found that in addition to cadmium, the
      activators of Nrf2, such as diethyl maleate (DEM) and arsenite, induced both
      TrxR1 and Trx gene expression in BAEC. Nrf2 might play an important role in the
      regulation of the cellular Trx system consisting of Trx and TrxR.

PMID- 15521074
TI  - Implications of structural genomics target selection strategies: Pfam5000, whole
      genome, and random approaches.
AB  - Structural genomics is an international effort to determine the three-dimensional
      shapes of all important biological macromolecules, with a primary focus on
      proteins. Target proteins should be selected according to a strategy that is
      medically and biologically relevant, of good value, and tractable. As an option
      to consider, we present the "Pfam5000" strategy, which involves selecting the
      5000 most important families from the Pfam database as sources for targets. We
      compare the Pfam5000 strategy to several other proposed strategies that would
      require similar numbers of targets. These strategies include complete solution of
      several small to moderately sized bacterial proteomes, partial coverage of the
      human proteome, and random selection of approximately 5000 targets from sequenced
      genomes. We measure the impact that successful implementation of these strategies
      would have upon structural interpretation of the proteins in Swiss-Prot, TrEMBL,
      and 131 complete proteomes (including 10 of eukaryotes) from the Proteome
      Analysis database at the European Bioinformatics Institute (EBI). Solving the
      structures of proteins from the 5000 largest Pfam families would allow accurate
      fold assignment for approximately 68% of all prokaryotic proteins (covering 59%
      of residues) and 61% of eukaryotic proteins (40% of residues). More fine-grained
      coverage that would allow accurate modeling of these proteins would require an
      order of magnitude more targets. The Pfam5000 strategy may be modified in several
      ways, for example, to focus on larger families, bacterial sequences, or
      eukaryotic sequences; as long as secondary consideration is given to large
      families within Pfam, coverage results vary only slightly. In contrast, focusing
      structural genomics on a single tractable genome would have only a limited impact
      in structural knowledge of other proteomes: A significant fraction (about 30-40%
      of the proteins and 40-60% of the residues) of each proteome is classified in
      small families, which may have little overlap with other species of interest.
      Random selection of targets from one or more genomes is similar to the Pfam5000
      strategy in that proteins from larger families are more likely to be chosen, but
      substantial effort would be spent on small families.

PMID- 15521075
TI  - Requirement of protein phosphatase 2A for recruitment of IQGAP1 to Rac-bound
      beta1 integrin.
AB  - Serine/threonine protein phosphatase (PP) 2A is thought to dephosphorylate
      phosphorylated beta1 integrin to link with actin filaments (F-actin). However,
      whether PP2A participates in the regulation of F-actin assembly to which beta1
      integrin is anchored is unclear. We report here that the core enzyme of PP2A
      (PP2A-AC), consisting of the regulatory subunit A (PP2A-A) and the catalytic
      subunit C (PP2A-C), forms a complex with beta1 integrin, a small GTPase Rac, and
      its effector IQGAP1 in non-malignant human mammary epithelial (HME) cells.
      Treatment of HME cells with okadaic acid (OA), an inhibitor of PP2A, caused cell
      rounding, reduction in F-actin assembly that links with beta1 integrin, and
      dissociation of IQGAP1-bound PP2A-AC from Rac-beta1 integrin. The dissociation of
      IQGAP1-PP2A-AC was accompanied by loss of F-actin gelating activity of Rac-beta1
      integrin. In breast cancer MCF-7 cells, which possess PP2A-C but lack PP2A-A,
      IQGAP1 was not associated with Rac-beta1 integrin but with PP2A-C, with no
      distinct F-actin assembly that linked to Rac-beta1 integrin even before treatment
      with OA. We therefore propose that PP2A, especially PP2A-A, functions to maintain
      F-actin assembly to which beta1 integrin is anchored by recruitment of IQGAP1 to
      Rac-beta1 integrin.

PMID- 15521076
TI  - Emergency ligation of the brachial artery for complications of vascular access.

PMID- 15521077
TI  - Radioisotope bone scans in the preoperative staging of hepatopancreatobiliary
      cancer.
AB  - BACKGROUND: The aim of the study was to determine the value of radioisotope bone
      scans in the preoperative staging of patients with hepatopancreatobiliary (HPB)
      cancer. METHODS: Bone scanning was performed as part of a routine staging
      protocol in 402 consecutive patients with HPB cancer over a period of 5 years.
      Patients with positive bone scans underwent coned radiography, computed
      tomography with review on bone windows, or a bone biopsy. Bone scans were
      reviewed along with staging investigations, surgical and histological findings.
      Patients were followed for a minimum of 6 months. RESULTS: There were 171
      patients with colorectal liver metastases, 106 with suspected pancreatic cancer,
      47 with hepatocellular cancer, 52 with gallbladder cancer or cholangiocarcinoma,
      and 26 with other types of HPB cancer. Bone scans were negative in 377 patients
      (93.8 per cent) and positive in 25 patients (6.2 per cent). Of the 25 positive
      scans, 16 were falsely positive as a result of degenerative bone disease. Of nine
      patients with a true-positive bone scan, four had locally irresectable disease
      and four distant metastases. In only one patient did the bone scan result alone
      influence the decision to resect the HPB cancer. Overall sensitivity was 100 per
      cent, specificity 95.9 per cent, positive predictive value 36.0 per cent and
      negative predictive value 100 per cent. CONCLUSION: Bone scanning should not be
      included in the routine staging protocol for HPB cancer.

PMID- 15521078
TI  - Long-term results and risk factors influencing outcome of major bile duct
      injuries following cholecystectomy.
AB  - BACKGROUND: Major bile duct injuries usually need operative repair and remain a
      challenge even for surgeons who specialize in hepatobiliary surgery. The purpose
      of this study was to evaluate management and short- and long-term outcomes of
      patients with major complications after cholecystectomy. METHODS: Data were
      analysed for 54 patients who underwent operation for major bile duct injuries
      after cholecystectomy between January 1990 and January 2002. Univariate and
      multivariate analyses were performed to identify risk factors for the development
      of biliary complications. RESULTS: Complete follow-up data were available for all
      54 patients (median duration 61.9 (range 2.6-154.3) months). All underwent Roux
      en-Y hepaticojejunostomy. Three patients (6 per cent) died from biliary tract
      complications during follow-up. Long-term biliary complications occurred in ten
      patients (19 per cent). Nine patients developed biliary stricture of whom five
      developed secondary biliary cirrhosis. A successful long-term result was achieved
      in 50 (93 per cent) of 54 patients, including those who required subsequent
      procedures. Biliary reconstruction in the presence of peritonitis (P = 0.002),
      combined vascular and bile duct injuries (P = 0.029), and injury at or above the
      level of the biliary bifurcation (P = 0.012) were significant independent
      predictors of poor outcome. CONCLUSION: Successful repair of bile duct injuries
      after cholecystectomy can be achieved in specialized hepatobiliary units.

PMID- 15521079
TI  - Randomized clinical trial of the effect of intravenous fluid administration on
      hormonal and renal dysfunction in patients with obstructive jaundice undergoing
      endoscopic drainage.
AB  - BACKGROUND: Renal dysfunction in patients with biliary obstruction is associated
      with extracellular water depletion. This study examined the effect of
      preoperative saline infusion before biliary drainage on hormonal and renal
      functional derangements in patients with obstructive jaundice. METHODS: In a
      randomized study, 49 patients with malignant obstructive jaundice were
      investigated at baseline, on the day of drainage, and at 24 h, 72 h and 7 days
      after internal endoscopic biliary drainage. Patients were randomized to receive
      (n = 22) or not to receive (n = 27) 3000 ml normal saline intravenously for 24 h
      before drainage. Variables analysed included extracellular water volume,
      creatinine clearance, and serum levels of aldosterone, renin, atrial natriuretic
      peptide (ANP), vasopressin and albumin. RESULTS: Preoperative saline infusion
      produced a rise in creatinine clearance, diuresis, ANP concentration and
      extracellular water volume but this did not translate into better recovery of
      renal function after operation. Drainage produced a fall in creatinine clearance
      in all patients, but hormonal and renal function had recovered by 2 days after
      restoration of bile flow, independently of preoperative hydration. CONCLUSION:
      Fluid administration expands the extracellular water compartment before drainage
      but fails to improve renal function after drainage. Definitive improvement in
      endocrine and renal function requires the restoration of bile flow into the
      duodenum.

PMID- 15521080
TI  - Early prediction of organ failure by combined markers in patients with acute
      pancreatitis.
AB  - BACKGROUND: Several biological markers and clinical scoring systems have been
      used to predict the course of acute pancreatitis. Because organ failure is the
      most severe complication of the disease, prognostic markers and their
      combinations that would predict organ failure on hospital admission were sought.
      METHODS: Some 351 consecutive patients with acute pancreatitis were studied.
      Blood samples were taken within 12 h of admission. This case-control study
      included all 33 patients with organ failure and 99 matched controls without organ
      failure. Measurements included 19 prognostic markers and Acute Physiology And
      Chronic Health Evaluation (APACHE) II score. RESULTS: Plasma interleukin 10,
      serum glucose and serum calcium were identified as independent predictors of
      organ failure by logistic regression analysis. Calcium level correlated with
      clinical onset of organ failure. The combination of interleukin 10 (more than 50
      pg/ml) or calcium (less than 1.65 mmol/l) was a significantly better predictor
      than any single marker or APACHE II score, with a sensitivity of 88 per cent,
      specificity 93 per cent and diagnostic odds ratio 94. CONCLUSION: Organ failure
      in acute pancreatitis can be predicted with high accuracy at hospital admission
      using a combination of plasma interleukin 10 and serum calcium measurements.

PMID- 15521081
TI  - Short-stay thyroid surgery.

PMID- 15521082
TI  - Hydrazine-induced post-chemiluminescence phenomenon of permanganate-luminol
      reaction and its applications.
AB  - The post-chemiluminescence phenomenon arising from the permanganate-luminol
      reaction induced by hydrazine and isoniazid was investigated. When hydrazine or
      isoniazid was injected into the mixture after the end of the reaction of
      permanganate with alkaline luminol, a new chemiluminescence (CL) reaction was
      initiated and strong CL signal was detected. A possible CL mechanism is
      suggested, based upon the studies of the kinetic characteristics of the CL
      reaction, the UV-visible spectra, the CL spectra and some other experiments. The
      present reactions allow the determination of 0.1-10.0 mg/L hydrazine and 0.02-1.0
      mg/L isoniazid, with detection limits of 0.03 mg/L and 0.006 mg/L, respectively.
      The method was applied to the determination of isoniazid in pharmaceutical
      preparations.

PMID- 15521083
TI  - Emergency surgery for colonic cancer in a defined population.
AB  - BACKGROUND: The aim of this study was to identify risk factors in emergency
      surgery for colonic cancer in a large population and to investigate the economic
      impact of such surgery. METHODS: Data from the colonic cancer registry (1997
      2001) of the Uppsala/Orebro Regional Oncological Centre were analysed and
      classified by hospital category. Some 3259 patients were included; 806 had an
      emergency and 2453 an elective procedure. Data for calculating effects on health
      economy were derived from a national case-costing register. RESULTS: Patients who
      had emergency surgery had more advanced tumours and a lower survival rate than
      those who had an elective procedure (5-year survival rate 29.8 versus 52.4 per
      cent; P < 0.001). There was a stage-specific difference in survival, with poorer
      survival both for patients with stage I and II tumours and for those with stage
      III tumours after emergency compared with elective surgery (P < 0.001). Emergency
      surgery was associated with a longer hospital stay (mean 18.0 versus 10.0 days; P
      < 0.001) and higher costs (relative cost 1.5 (95 per cent confidence interval 1.4
      to 1.6)) compared with elective surgery. The duration of hospital stay was the
      strongest determinant of cost (r(2) = 0.52, P < 0.001). CONCLUSION: Emergency
      surgery for colonic cancer is associated with a stage-specific increase in
      mortality rate.

PMID- 15521084
TI  - Renal impairment in cystic fibrosis patients due to repeated intravenous
      aminoglycoside use.
AB  - Although there are reports of cases of acute renal failure occurring in cystic
      fibrosis (CF) patients, usually in association with the use of nephrotoxic
      antibiotic therapy, there have been no studies of renal function in this patient
      group. We hypothesized that long-term use of intravenous (IV) nephrotoxic
      antibiotics (aminoglycosides and colistin sulphomethate) may contribute to renal
      disease in CF patients. In a prospective study, we assessed creatinine clearance
      as an index of renal function with two techniques (24-hr urine collections and
      the Cockroft-Gault formula) in a group of 80 stable adult CF outpatients
      chronically infected with Pseudomonas aeruginosa but with no history of preceding
      renal disease. Using a multiple linear regression model, we evaluated their renal
      function in terms of their lifetime IV use of aminoglycosides and colistin.
      Between 31% (Cockroft-Gault formula method) and 42% (24-hr urine collection
      method) of patients had a creatinine clearance below normal range. Using either
      method, there was a strong correlation between aminoglycoside use and diminishing
      renal function (r=- 0.32, P=0.0055), which was potentiated by the
      coadministration of colistin (r=- 0.42, P <0.0002). However, there was no
      correlation with colistin when used in combination with other antibiotics alone
      (r=0.18, P=NS). Repeated IV aminoglycoside use in CF is associated with long-term
      renal damage. Although this effect is potentiated by colistin, colistin on its
      own in moderate doses does not appear to be nephrotoxic. IV aminoglycosides
      should be used cautiously in CF patients, with regular monitoring of renal
      function.

PMID- 15521086
TI  - Three- and four-dimensional reconstruction of the aortic and ductal arches using
      inversion mode: a new rendering algorithm for visualization of fluid-filled
      anatomical structures.

PMID- 15521085
TI  - Increased lung matrix metalloproteinase-9 levels in extremely premature baboons
      with bronchopulmonary dysplasia.
AB  - Matrix metalloproteinases (MMPs) regulate the formation of normal lung
      architecture. Extremely premature infants exposed to hyperoxia and mechanical
      ventilation often develop lung inflammation and injury. We hypothesized that an
      imbalance between MMPs and their tissue inhibitors plays a key role. Our
      hypothesis was tested to: 1) examine the ontogeny of lung MMPs and tissue
      inhibitors of metalloproteinases (TIMPs); and 2) determine the effects of
      hyperoxia and mechanical ventilation on lung MMPs and TIMPs in premature newborn
      baboons developing chronic lung disease/bronchopulmonary dysplasia (CLD/BPD).
      Lung specimens were obtained from five groups of gestational controls (GCs)
      sacrificed at 125, 140, 160, 175, and 185 (term) days of gestation, one fetal
      baboon model of CLD/BPD delivered at 125 days, and two at 140 days of gestation.
      Paraffin-embedded lung tissue sections were examined for pathological changes,
      and frozen lung specimens were analyzed for MMPs-1, -2, -8, and -9; TIMPs-1 and 
      2; and messenger RNA expression of type I collagen. In GCs, MMP-1 and -9 were
      elevated in the last trimester, whereas MMP-2 and -8 levels were decreased.
      Significant changes in lung architecture were noted in the BPD models. MMP-1 was
      increased in the 125-day model, but decreased in both 140-day models. MMP-8 and
      collagen mRNA levels were decreased, while MMP-9 and MMP-9 to TIMP-1 ratios were
      increased in all BPD models. We conclude that an imbalance between MMP-9 and TIMP
      1 leading to excessive MMP-9 activity contributes to lung inflammation and edema
      in CLD/BPD.

PMID- 15521087
TI  - Xanthoma disseminatum: a child with respiratory system involvement and
      bronchiectasis.
AB  - Xanthoma disseminatum (XD) is a rare normolipemic mucocutaneous xanthomatosis due
      to the proliferation of non-x histiocytes. Occasional involvement of the upper
      respiratory system has been reported, but lower respiratory tract involvement is
      very rare. Here, we present a child with severe involvement of the upper and
      lower respiratory tract by XD and bronchiectasis in the lower lobes of both
      lungs. The patient was an 8-year-old boy who was admitted to our hospital because
      of red-brown papules which developed on the skin and progressive dyspnea. He was
      diagnosed as having XD by skin biopsy. Physical examination revealed
      disseminated, numerous yellow-reddish brown papular xanthomas on the forehead and
      eyelids, around the neck and axillary area, and in the oral cavity and pharynx.
      He had respiratory distress and clubbing of the fingers. Chest x-rays showed
      hyperaeration and segmental atelectasis. High-resolution CT of the thorax
      revealed diffuse thickening of the whole tracheal and bronchial wall, and
      bronchiectasis in the lower lobes. Flexible fiberoptic bronchoscopy revealed
      numerous xanthomatous lesions in the nasal cavity, nasopharynx, oropharynx,
      subglottic area, trachea, bifurcation, both main bronchi, and smaller bronchi. To
      the best of our knowledge, this is the first report of a child with typical
      lesions of XD with severe involvement of the lower respiratory tract and
      bronchiectasis.

PMID- 15521089
TI  - Ab initio quantum mechanical study of the binding energies of human estrogen
      receptor alpha with its ligands: an application of fragment molecular orbital
      method.
AB  - We have theoretically examined the relative binding affinities (RBA) of typical
      ligands, 17beta-estradiol (EST), 17alpha-estradiol (ESTA), genistein (GEN),
      raloxifene (RAL), 4-hydroxytamoxifen (OHT), tamoxifen (TAM), clomifene (CLO), 4
      hydroxyclomifene (OHC), diethylstilbestrol (DES), bisphenol A (BISA), and
      bisphenol F (BISF), to the alpha-subtype of the human estrogen receptor ligand
      binding domain (hERalpha LBD), by calculating their binding energies. The ab
      initio fragment molecular orbital (FMO) method, which we have recently proposed
      for the calculations of macromolecules such as proteins, was applied at the
      HF/STO-3G level. The receptor protein was primarily modeled by 50 amino acid
      residues surrounding the ligand. The number of atoms in these model complexes is
      about 850, including hydrogen atoms. For the complexes with EST, RAL, OHT, and
      DES, the binding energies were calculated again with the entire ERalphaLBD
      consisting of 241 residues or about 4000 atoms. No significant difference was
      found in the calculated binding energies between the model and the real protein
      complexes. This indicates that the binding between the protein and its ligands is
      well characterized by the model protein with the 50 residues. The calculated
      binding energies relative to EST were very well correlated with the experimental
      RBA (the correlation coefficient r=0.837) for the ligands studied in this work.
      We also found that the charge transfer between ER and ligands is significant on
      ER-ligand binding. To our knowledge, this is the first achievement of ab initio
      quantum mechanical calculations of large molecules such as the entire ERalphaLBD
      protein.

PMID- 15521094
TI  - Engineered Streptomyces quorum-sensing components enable inducible siRNA-mediated
      translation control in mammalian cells and adjustable transcription control in
      mice.
AB  - BACKGROUND: Recent advances in functional genomics, gene therapy, tissue
      engineering, drug discovery and biopharmaceuticals production have been fostered
      by precise small-molecule-mediated fine-tuning of desired transgenes. METHODS:
      Capitalizing on well-evolved quorum-sensing regulatory networks in Streptomyces
      coelicolor we have designed a mammalian regulation system inducible by the non
      toxic butyrolactone SCB1. Fusion of the S. coelicolor SCB1 quorum-sensing
      receptor ScbR to the human Kox-1-derived transsilencing domain reconstituted a
      mammalian transsilencer (SCS) able to repress transcription from SCS-specific
      operator-containing promoters in a reverse SCB1-adjustable manner. RESULTS: This
      quorum-sensing-derived mammalian transgene control system (Q-ON) enabled precise
      SCB1-specific fine-tuning of (i) desired transgene transcription in a variety of
      mammalian/human cell lines and human primary cells, (ii) small interfering RNA
      mediated posttranscriptional knockdown (siRNA) in mammalian cells, and (iii)
      dosing of a human glycoprotein in mice. CONCLUSIONS: As exemplified by Q-ON
      technology, bacterial quorum-sensing regulons may represent a near-infinite
      source for the design of mammalian gene control systems compatible with molecular
      interventions relevant to future gene therapy and tissue engineering scenarios.

PMID- 15521095
TI  - FVIII gene delivery by muscle electroporation corrects murine hemophilia A.
AB  - BACKGROUND: Hemophilia A treatment relies on costly factor VIII (FVIII)
      replacement that may transmit iatrogenic viral diseases. Viral vectors and cell
      implants are being developed as improvements. We investigated in vivo
      electroporation of naked DNA as a safe and simple method for correcting FVIII
      deficiency. METHODS: B-domain-deleted murine FVIII cDNA expression plasmids were
      constructed with CMV and elongation factor 1alpha promoters for characterisation
      in murine C2C12 myoblasts. The construct conferring highest in vitro FVIII
      secretion was electroporated into skeletal muscle of FVII null mice in vivo for
      phenotypic correction using a protocol that minimised tissue injury. RESULTS: B
      domain-deleted murine FVIII cDNA plasmids induced FVIII secretion from stably
      transfected C2C12 myoblasts (0.54+/-0.20 mU/day/10(5) cells). Phenotypic
      correction of hemophilic mice was more consistently achieved using a protocol for
      in vivo electroporation of gastrocnemius muscle with FVIII cDNA that reduced
      tissue injury by the use of plate electrodes, hyaluronidase pre-treatment and
      lower field strength. This technique was associated with <10% muscle necrosis.
      Activated partial thromboplastin time decreased from 51.4+/-3.3 to 34.7+/-1.1
      (mean+/-s.e.m.) seconds (p=0.0004) following in vivo electroporation (0.1 mg
      plasmid/limb; 8x20 ms pulses, 175 V/cm, 1 Hz) of hemophilic mice. All hemophilic
      mice (8/8) survived hemostatic challenge after muscle electroporation with FVIII
      cDNA, whereas all (9/9) untreated hemophilic mice died. Plasmid DNA was
      detectable only in electroporated muscle and not in all other organs tested,
      including gonads. CONCLUSION: In vivo intramuscular electroporation of naked
      FVIII plasmid successfully corrects murine hemophilia.

PMID- 15521096
TI  - Swiss patent proposal prompts criticism.

PMID- 15521098
TI  - Battle against malaria.

PMID- 15521097
TI  - What every CFO should know about equipment financing.

PMID- 15521099
TI  - More WHO Member States unite in fight against skin cancer caused by excessive
      exposure to UV radiation.

PMID- 15521100
TI  - New edition of WHO prequalification list to include four new anti-AIDS medicines.

PMID- 15521103
TI  - [Bacterial meningitis caused by Neisseria meningitidis. Prophylactic measures].
AB  - Meningitis caused by Neisseria meningitidis is one of the most frequent and most
      serious, with fatal rate between few up to 20%. Majority of cases are caused by
      Neisseria meningitidis of serological groups A, B, C, as well as Y and W 135.
      Vaccination is the most effective prophylactic measure against meningococcal
      meningitidis. Polysaccharide, not conjugated vaccines against Neisseria
      meningitidis serological groups A, C, W 135, Y effective for children over 2
      years old, adolescents and adults as well as vaccine against serogroup C
      conjugated with protein carrier, effective for children over 2 months of life,
      adolescents and adults are used. Conjugated vaccine against serological group C
      was used in 1998/1999 in Great Britain in the mass vaccination of infants in 2,
      3, 4 months of life, children and adolescents up to 17. In Poland as well as in
      other European countries serological group B is an etiological factor of majority
      of cases caused by Neisseria meningitidis. Intensive studies are performed in the
      field on effective, safety, cheap vaccine against all serological groups of
      Neisseria meningitidis.

PMID- 15521102
TI  - Osteoprotegerin production by human intestinal epithelial cells: a potential
      regulator of mucosal immune responses.

PMID- 15521104
TI  - Hypotriploidy 68,XX: a new case report and review of earlier cases.
AB  - We report a prematurely born patient with a 68,XX karyotype. She presented with
      syndactyly of 2nd and 3rd toes, minor facial features, microcephaly, slender
      hands, bicuspid aortic valve, patent ductus arteriosus and hypotonia. Comparison
      with other reported cases is given.

PMID- 15521105
TI  - Deletions on chromosome 4 in sporadic and BRCA mutated tumors and association
      with pathological variables.
AB  - BACKGROUND: Chromosomal aberrations in breast tumors from BRCA1 and BRCA2 germ
      line mutation carriers are considerably more frequent than what is seen in
      sporadic breast tumors. According to Comparative Genomic Hybridisation analysis
      (CGH), deletions on chromosome 4 are one of the most frequent events in BRCA1
      associated tumors, suggesting inactivation of specific tumor suppressor genes.
      MATERIALS AND METHODS: In the present study, 16 microsatellite markers covering
      chromosome 4 were used to map loss of heterozygosity (LOH) in tumors from BRCA1
      (n=41) as well as in tumors from BRCA2 (n=66) mutation carriers and in tumors
      from unselected cases of breast cancer (n =68). RESULTS: The frequency of LOH in
      these groups ranged from 16-73% in BRCA1-associated tumors, 13-42% in BRCA2
      associated tumors and 8-33% in unselected tumors. LOH was significantly more
      frequent in BRCA1-associated tumors as compared to BRCA2-associated tumors and
      unselected tumors, and particularly high (over 70%) at 4q35.2. Pathological
      variables that were found significantly associated (p< or =0.05) with LOH at
      specific markers were: high percentage of cells in S-phase, negative estrogen
      receptor status, young age at diagnosis and large tumors. Deletion mapping
      indicates the existence of seven non-overlapping regions at chromosome 4, which
      were identified in all three groups of tumors. Three of these seven regions,
      4p16.3-p16.1, 4q27-q32.1 and 4q35.1-4qter, have not been reported in breast
      cancer previously. CONCLUSION: The results manifest the frequent alterations of
      chromosome 4 in BRCA1-associated breast tumors and indicate the location of
      several genes of potential importance in breast cancer development.

PMID- 15521106
TI  - The efficacies of affected-limb care with penicillin diethylcarbamazine, the
      combination of both drugs or antibiotic ointment, in the prevention of acute
      adenolymphangitis during bancroftian filariasis.
AB  - Repeated attacks of adenolymphangitis (ADL) contribute significantly to the
      progression of chronic lymphoedema in lymphatic filariasis. They are a cause of
      stigma and, since they may prevent work and require treatment for which payment
      must be made, of economic loss. The aim of the present study was to improve the
      treatment of ADL attacks, which is currently mostly empirical. In a double-blind,
      placebo-controlled, clinical study, 150 subjects who had each suffered at least
      two ADL attacks in the preceding year were enrolled and randomly allocated to a
      programme of self-care of the affected limb (after an intensive training
      programme) and one of five treatments for 12 months. The subjects were supplied
      with tablets and ointment so that they could take oral penicillin (800 mg/day),
      oral diethylcarbamazine (DEC; 1 mg/kg.day) or both of these drugs (at the same
      doses), or apply framycetin ointment to the affected limb, or just take placebo
      tablets and apply placebo (zinc-oxide) ointment. Placebo tablets and placebo
      ointment were used so that neither the subjects nor those assessing the responses
      to treatment were aware of the treatment arm to which each subject had been
      assigned. The subjects were requested to continue with the affected-limb care
      after they had stopped taking the tablets and applying the cream, and were
      followed-up for 24 months from the first treatment.Overall, the mean incidence of
      ADL attacks decreased from 2.7 episodes/person-year in the pre-treatment year to
      just 0.38 episode/person-year during the treatment year (P< 0.01). The greatest
      reduction in incidence was seen in the 58 subjects who received penicillin (with
      or without DEC). Even in the placebo group, however, the incidence of ADL in the
      treatment year was significantly lower than that seen in the pre-treatment year,
      indicating that affected-limb care on its own helps to prevent some attacks. In
      all groups except the placebo, the incidence of ADL attacks in the year post
      treatment exceeded that seen in the treatment year, indicating that
      chemoprophylaxis needs to be continued for more than a year if such attacks are
      to be prevented. In most (84%) of the attacks recorded, titres of anti
      streptococcal antibodies were seen to be elevated (compared with those recorded
      during convalescence),indicating that streptococci have a role in the aetiology
      of ADL. It is recommended that a combination of penicillin prophylaxis and
      affected-limb care be incorporated into filariasis-control programmes, to
      decrease morbidity.

PMID- 15521107
TI  - A need for faculty development in developmental and behavioral pediatrics.
AB  - Identifying and managing issues of child development and behavior is a crucial
      part of primary care pediatrics. Despite its importance, many pediatricians do
      not receive adequate training in developmental and behavioral pediatrics (DBP).
      In a Web-based survey, general pediatric faculty reported a need for improved
      resident education and additional faculty development. Only 4 percent of
      respondents felt the quality of current residency training in DBP was excellent
      and most (64%) felt that too little time was devoted to training in this subject.
      Nearly all the respondents agreed that increasing faculty skills in this area
      would significantly improve residents' training but cited the lack of release
      time (67%) and funding (74%) to attend continuing education as important
      barriers. To improve faculty skills and resident training, the authors recommend
      expanding the scope of DBP fellowship programs to include faculty development and
      making faculty development a regular expectation within academic pediatrics.

PMID- 15521108
TI  - CHEST 2004. October 23-28, 2004, Seattle, Washington, USA. Abstracts.

PMID- 15521109
TI  - Abstracts of the 22nd Conference of European Comparative Endocrinologists. 24-28
      August 2004, Uppsala, Sweden.

PMID- 15521110
TI  - [The informed citizen].

PMID- 15521112
TI  - Tennessee Dental Association directory and membership roster, 2004-2005.

PMID- 15521111
TI  - [The well-informed patient from the statutory health insurance standpoint].
AB  - By introducing competition into the statutory health insurance system the model
      of the informed patient has obtained new importance. As corporations of public
      law,more than 350 statutory health insurance funds (SHI funds) fulfil original
      tasks of in-forming and counselling patients. Although the SHI funds lack
      incentives for more patient orientation due to an inadequate risk equalization
      scheme, the SHI funds are extending their competences to support health consumer
      protection. On the one hand, attractive offers for information and counselling
      are being regarded as an important competitive field in the framework of the
      respective corporate strategy. On the other hand, the SHI funds are highly
      interested in having well-informed patients assume personal responsibility and
      through their well-directed demands contribute to more quality and efficiency in
      the healthcare system. Which objective need for in-formation does the population
      still have?What are the effects of medical lay knowledge on the communication
      between doc-tor and patient? From the SHI funds' point of view, however, there
      are many relevant questions still unsolved. Therefore, they consider health care
      research desirable to help them make user-oriented information avail-able for
      different target groups.

PMID- 15521113
TI  - [Significance of information for cancer patients and the experience of the German
      Cancer Information Service in Heidelberg].
AB  - Cancer patients have a great need for information. Besides the attending
      physician as the most valued source of information they use various other
      sources. The broad avail-ability of information raises the need for "meta
      information" for assessment, explanation and integration into the individual
      context. Here, a telephone information ser-vice meeting high quality standards
      can of-fer substantial support, combining the advantages of mass media with
      interpersonal communication. The cancer information ser-vice (KID), established
      at the German Can-cer Research Center in 1986 with funding by the Federal
      Ministry of Health, has implemented this concept of health information for the
      first time on a national basis. The KID provides comprehensive and up-to-date
      information on all cancer-related issues tailored to individual needs as well as
      address-es and resources of institutions and organisations of cancer care. Around
      40% of KID users are patients. Major concerns are reassurance, assessment and
      integration of information from other sources, the need for guidance through the
      health care system and for supportive communication.Tele-phone information can
      bridge information gaps and deficits and enhance the doctor-patient relationship
      by building a basis for in-depth discussions. To meet the needs and new
      information preferences, the KID also publishes brochures and offers information
      via the Internet and an e-mail service. The KID is integrated in a network of can
      cer care resources and, through documentation and evaluation of the calls,
      contributes to cancer information tailored to the needs of patients.

PMID- 15521114
TI  - [Influence of human genetic variants on resistance and immunity against malaria].
AB  - Certain human genetic variants occur on-ly in areas endemic for malaria. They
      protect against fatal malaria complications and cause inhibition of growth or
      development of malaria parasites in vitro. Among these are the haemoglobins (Hb)
      S and C, alpha-thalassaemias, glucose-6-phosphate dehydrogenase deficiency, as
      well as a deletion in the erythrocyte band 3 protein. Evidence for similar
      effects has been obtained for HbD and HbE, glycophorins A and C as well as for a
      number of immunologically relevant molecules such as human leukocyte
      antigens,tumour-necrosis-factor a and the inducible nitric oxide synthase. The
      findings indicate that malaria in endemic areas has caused a substantial
      selection of the human genome.

PMID- 15521115
TI  - [Shared decision making (SDM) with chronic pain patients. The patient as a
      partner in the medical decision making process].
AB  - Fibromyalgia syndrome (FMS) is an exemplary condition of chronic widespread pain
      that is difficult to control and often leads to frustration and resignation on
      the part of both the patient and the doctor. Shared decision making (SDM) could
      be a means to facilitate doctor-patient interaction and might therefore influence
      therapeutic decisions taken. We conducted a prospective study to evaluate the
      effects of SDM with FMS patients. We developed a communication train-ing program
      for physicians and a computer-based information tool on FMS for patients. The
      study included 133 FMS patients. Intervention group I (IG I) was treated by
      communication-trained doctors and had access to a computer-based information tool
      on FMS,intervention group II (IG II) was treated by standard doctors and received
      the information tool, and the control group (CG) was treated by standard doctors
      and got no additional information. All three groups we-re offered the same
      evidence-based treatment options for FMS. Patients of the IGs were more willing
      to become involved in exercise, to enroll in integrated group therapy for FMS
      patients (IGTF), and to take analgesics. Patients of the CG preferred anti
      depressants. More patients from IG II and CG opted for relaxation techniques.
      Patients in IG I and IG II choose significantly more therapeutic options than
      patients in the CG. SDM is one means to increase FMS patients' readiness for
      treatment. Especially the element of providing sufficient medical information
      seems to account for this effect. The readiness to enroll in physical activities,
      to take analgesics, and to participate in psychotherapeutic elements was most
      likely to be raised through SDM.

PMID- 15521116
TI  - Abstracts of the Annual Meeting of the German, Austrian, and Swiss Societies of
      Hematology and Oncology. Innsbruck, Austria, 2-6 October 2004.

PMID- 15521117
TI  - [11th WaBoLu interior meeting, May 17-19, 2004. Summary of the most important
      results].

PMID- 15521118
TI  - [Report on the 7th Xenotransplantation Mini-Symposium at the Robert Koch
      Institute, Berlin, June 2004].

PMID- 15521119
TI  - Abstracts of the Annual Meeting of the Irish Cardiac Society. 30 September-2
      October 2004, Derry, Ireland.

PMID- 15521120
TI  - Abstracts of the 11th Annual Conference of the International Society for Quality
      of Life Research. October 16-19, 2004, Hong Kong.

PMID- 15521121
TI  - Abstracts of the XVII Annual Meeting of the Latin-American Society of Pediatric
      Endocrinology (SLEP). 24-28 October 2004, Angra dos Reis, Brazil.

PMID- 15521122
TI  - [Nitrates in drinking water. Preventive measures gem. 9 TrinkwV 2001 in non
      compliance with threshold limit values and requirements for nitrates and nitrites
      in drinking water].

PMID- 15521123
TI  - Abstracts of the 1st Global Conference on Cardiovascular Clinical Trials and
      Pharmacotherapy. October 1-3, 2004.

PMID- 15521125
TI  - [Abstracts of the 21st Annual Meeting of the Brazilian Society of Odontology
      Research. Aguas de Lindoia, Brazil, 8-12 September 2004].

PMID- 15521124
TI  - EUFEPS 2004. Abstracts of the 8th European Congress of Pharmaceutical Sciences.
      October 17-20, 2004. Brussels, Belgium.

PMID- 15521126
TI  - The 16th Annual Meeting of the Winter Conference on Neural Plasticity. St. Lucia,
      West Indies. February 21-28, 2004.

PMID- 15521127
TI  - The 9th International Conference on Alzheimer's Disease and Related Disorders.
      Philadelphia, PA. July 17-22, 2004.

PMID- 15521128
TI  - Hypertension, hyperlipidemia and stroke. Utilizing evidence to improve outcome.
      New York Academy of Medicine Symposium. May 17-18, 2004.

PMID- 15521129
TI  - Symposia at the 19th Annual Meeting of American Society of Hypertension. New
      York, May 19, 2004.

PMID- 15521130
TI  - More on seclusion and restraint.

PMID- 15521131
TI  - JCAHO and alternative therapy.

PMID- 15521132
TI  - Trauma and dissociation.

PMID- 15521133
TI  - The future of advanced practice psychiatric nursing.

PMID- 15521134
TI  - The meaning of mental health from elderly women's perspectives: a basis for
      health promotion.
AB  - PROBLEM: To gain a deeper understanding of the meaning of mental health. METHODS:
      Qualitative interviews with 16 women between the ages of 71 and 92. The data were
      collected and analyzed using a phenomenological approach. FINDINGS: The essence
      of mental health is the experience of confirmation, trust and confidence in the
      future, as well as a zest for life, development, and involvement in one's
      relationship to oneself and to others. CONCLUSIONS: Creating arenas for
      encounters confirming the individual's human existence and dignity is an
      important basis for the psychiatric nurse's health-promotion work.

PMID- 15521135
TI  - Settling into and moving in a climate of care: styles and patterns of interaction
      between nurse psychotherapists and clients.
AB  - PURPOSE: To study nonverbal manifestations of rapport between nurse
      psychotherapists and clients. METHODS: A phenomenological investigation of eight
      pairs of nurse psychotherapists and clients was completed using video-cued
      narrative recall. FINDINGS: Emotional congruence, physical mirroring of gestures,
      postures, expressions, and shared cadences were significant to the participants.
      Matching behaviors were responsive, not technique-driven, and occurred only at
      meaningful junctures. Matching behaviors showed up simultaneously and as turn
      taking responses, and felt genuine because they incorporated imperfection and
      were expressed in varied ways. Settling into the climate of the client's world
      and matching her response helped the nurse therapist shape intervention
      possibilities, create a comfortable sense of timing, and establish rapport.
      CONCLUSIONS: Video-cued narrative recall was an effective research strategy.

PMID- 15521136
TI  - Therapeutic approaches to anxiety--a holistic view.
AB  - This then, briefly provides an example of how a number of different techniques
      can be woven into the treatment process, and how relaxation approaches
      particularly can be used. Practitioners who can be flexible in their approach,
      providing both mind and body techniques to help the client explore their anxiety,
      will find a deeper dimension to their work.

PMID- 15521138
TI  - Damage control. A crackdown to prevent conflicts of interest at the NIH.

PMID- 15521137
TI  - Drugs used for cognitive symptoms of Alzheimer's disease.
AB  - AD is a devastating disease that is increasing in real numbers as our population
      ages. The toll on individuals, families, health care, and society will continue
      to escalate unless more effective treatment approaches are developed. To date,
      the most effective treatments are those that increase brain ACh levels by
      retarding the enzymatic breakdown of this neurotransmitter. These agents have
      proved modestly effective but are far from being the answer to AD. Further, when
      these drugs are withdrawn, patients rapidly decompensate to the state of
      disability suffered by those receiving placebo, indicating the deteriorative
      process continues unabated. The long-term effects on cognition of these drugs
      also is not known, but most clinicians are not overly optimistic. Other
      pharmacologic approaches include vitamin E, ginkgo biloba, estrogen, and the
      nonsteroidal anti-inflammatory drugs. Clinical trials do not robustly support
      their efficacy at this time, but there are numerous anecdotal reports to promote
      any or all of these approaches. Newer strategies under study include antiamyloid
      agents and nootropics (which enhance neuronal metabolic activity). The value of
      these approaches remains to be confirmed.

PMID- 15521140
TI  - Volcanic sniffing. Quantum-cascade laser may detect impending eruptions.

PMID- 15521139
TI  - Breathing with hepatitis. Does exposure to a liver-inflaming virus prevent
      asthma?

PMID- 15521141
TI  - Flawed revelations? Contamination may undermine genesis data.

PMID- 15521142
TI  - Connection blues. A hole for external control of bluetooth devices.

PMID- 15521143
TI  - Getting sicker. State budget constraints threaten public health.

PMID- 15521144
TI  - Flying carpets and scientific prayers. Scientific experiments claiming that
      distant intercessory prayer produces salubrious effects are deeply flawed.

PMID- 15521145
TI  - What's in a name? Not much at the moment, thinks biologist Kevin de Queiroz, but
      names could be made to reflect our modern understanding of life's origins and
      complexity.

PMID- 15521147
TI  - Black hole computers.

PMID- 15521146
TI  - Rebuilding broken hearts. Biologists and engineers working together in the
      fledgling field of tissue engineering are within reach of one of their greatest
      goals: constructing a living human heart patch.
AB  - A heart broken by love usually heals with time, but damage to cardiac muscle
      caused by a heart attack gets progressively worse. Unlike liver or skin, heart
      tissue cannot regenerate, so the scar left after a heart attack remains a
      noncontractile dead zone.

PMID- 15521148
TI  - Abrupt climate change.

PMID- 15521150
TI  - Computing at the speed of light.

PMID- 15521149
TI  - Holes in the missile shield. The national missile defense now being deployed by
      the U.S. should be replaced with a more effective system.

PMID- 15521151
TI  - Music and the brain.

PMID- 15521152
TI  - A split at the core.

PMID- 15521154
TI  - How do scientists know the composition of Earth's interior?

PMID- 15521153
TI  - Working knowledge. Keep the beat.

PMID- 15521155
TI  - How does decanting red wine affect its taste? And why not decant white?

PMID- 15521156
TI  - Health information technology as a tool to improve care for acute respiratory
      infections.

PMID- 15521157
TI  - What to do when it's you: Bill Clinton and hospital report cards.

PMID- 15521158
TI  - Increasing adherence to a community-based guideline for acute sinusitis through
      education, physician profiling, and financial incentives.
AB  - OBJECTIVES: To implement a large-scale multifaceted intervention consisting of
      physician education, profiling, and a financial incentive, to improve treatment
      quality for acute sinusitis. STUDY DESIGN: Cohort trial using a historical
      control of treatment patterns among approximately 500 internists, 200 family
      practitioners, and 200 pediatricians in a northeastern community-wide individual
      practice association. PARTICIPANTS AND METHODS: Episode treatment group methods
      were adapted to identify cases (episodes) and to assess care patterns for acute
      sinusitis among 420,000 health maintenance organization patients seen between
      January 1, 1999, and December 31, 2001. The intervention consisted of care
      pathway development, physician and patient education, physician profiling, and a
      financial incentive. RESULTS: A statistical process control chart showed a shift
      toward recommended treatment patterns after our intervention. The rate of
      exceptions per episode of acute sinusitis decreased 20%, from 326 exceptions per
      1000 episodes between January 1, 1999, and October 31, 2000, to 261 between
      November 1, 2000, and December 31, 2001. Decreased use of less effective or
      inappropriate antibiotics accounted for most of the change (199 to 136 exceptions
      per 1000 episodes [32% change]). Azithromycin use decreased 30%, from 97 to 68
      prescriptions per 1000 episodes. Firstline antibiotic (amoxicillin and
      doxycycline) use increased 14%, from 451 to 514 prescriptions per 1000 episodes.
      Inappropriate radiology use decreased 20%, from 15 to 12 per 1000 episodes. These
      changes were significant at P < .005. CONCLUSION: A multifaceted program,
      including education, physician profiling with actionable recommendations, and a
      financial incentive, significantly increased physicians' adherence to a community
      developed care pathway and was successful at improving adherence to recommended
      patterns of antibiotic use in acute sinusitis.

PMID- 15521159
TI  - Improving care for nursing home-acquired pneumonia in a managed care environment.
AB  - OBJECTIVE: To characterize care of nursing home residents who became ill with
      nursing home-acquired pneumonia (NHAP) in a group-model, nonprofit HMO, and to
      pilot-test a strategy to implement evidence-based NHAP care guidelines. STUDY
      DESIGN: Medical record review and intervention pilot test. METHODS: Nursing home
      medical records of 78 patients who developed NHAP in 6 homes where the HMO
      contracts for Medicare services were reviewed for demographics, functional
      status, comorbidity, NHAP severity, care processes, and guideline compliance. The
      intervention, combining organizational change (facilitating immunization and
      providing appropriate emergency antibiotics) and education (quarterly in-services
      for nursing and aide staff), was pilot-tested for 7 months in 1 facility.
      Measures of baseline and intervention guideline adherence at that facility were
      compared with Fisher's exact test. RESULTS: Among the patients with NHAP, 83% had
      a response from their physician in less than 8 hours, 82% were treated with an
      antibiotic that met spectrum recommendations, and 74% were able to swallow were
      treated with oral antibiotics. However, few patients had documentation of
      influenza and pneumococcal vaccination; less than half the direct care staff had
      been vaccinated; and nursing assessments were incomplete for 23%. At the pilot
      test facility, improvement was seen in influenza vaccination (14% to 52%, P =
      .01) and use of the most appropriate antibiotics (47% to 85%; P = .03). The
      guideline adherence score improved from 52% to 63% (P = .04). CONCLUSION: Use of
      a multidisciplinary, multifaceted intervention resulted in improvement in quality
      of care for nursing home residents who become ill with pneumonia.

PMID- 15521160
TI  - Acute exacerbation of chronic bronchitis: a primary care consensus guideline.
AB  - OBJECTIVE: To develop consensus on appropriate treatment for acute exacerbation
      of chronic bronchitis (AECB). CHARACTERISTICS AND ETIOLOGY: Patients with chronic
      bronchitis have an irreversible reduction in maximal airflow velocity and a
      productive cough on most days of the month for 3 months over 2 consecutive years.
      An AECB is characterized by a period of unstable lung function with worsening
      airflow and other symptoms. Most (80%) cases of AECB are due to infection, with
      half due to aerobic bacteria. The remaining 20% are due to noninfectious causes
      such as environmental factors or medication nonadherence. MANAGEMENT: Supportive
      care should be provided to all patients, which might include removal of
      irritants, use of a bronchodilator, oxygen, hydration, use of a systemic
      corticosteroid, and chest physical therapy. Antibacterial treatment should be
      reserved for patients with at least 1 key symptom (ie, increased dyspnea, sputum
      production, sputum purulence) and 1 risk factor (ie, age > or = 65 years, forced
      expiratory volume in 1 second < 50% of the predicted value, > or = 4 AECBs in 12
      months, 1 or more comorbidities). A newer macrolide, extended-spectrum
      cephalosporin, or doxycycline is appropriate for an exacerbation of moderate
      severity, and high-dose amoxicillin/clavulanate or a respiratory fluoroquinolone
      should be used for a severe exacerbation. There has been increasing antibacterial
      resistance by the 3 most prevalent pathogens (Streptococcus pneumoniae,
      Haemophilus influenzae, and Moraxella catarrhalis). CONCLUSION: Although all AECB
      patients should receive supportive care, only patients with at least 1 key
      symptom and 1 risk factor should receive antibiotic therapy.

PMID- 15521161
TI  - Effect of the frequency of delivery of reminders and an influenza tool kit on
      increasing influenza vaccination rates among adults with high-risk conditions.
AB  - OBJECTIVE: To evaluate the incremental effect of a second client reminder
      postcard or an influenza tool kit targeted toward employers on increasing
      influenza vaccination rates among adults age < 65 years at high risk for
      complications from influenza illness. METHODS: In this demonstration study,
      enrollees of 3 managed care organizations (n = 8881) were randomized at the
      employer level into 4 arms: 1 postcard, 2 postcards, 1 postcard + tool kit, and 2
      postcards + tool kit. The postcards and tool kits were mailed during the fall of
      2001, and their effect on influenza vaccination rates was assessed through a
      survey. RESULTS: Compared with a single postcard, 2 postcards increased
      vaccination rates by 4 percentage points (adjusted relative risk = 1.05; P < .05)
      among persons aged 50 to 64 years but did not have any effect among younger
      adults. Older adults had a greater burden of disease and reported more favorable
      knowledge and attitudes toward the influenza vaccine. The influenza tool kit did
      not appear to have any incremental effect on vaccination rates. CONCLUSIONS: Our
      findings underscore the necessity of evaluating the effectiveness of
      interventions in different population subgroups and of identifying factors that
      modify the effectiveness of interventions. Rigorous assessment of intervention
      effectiveness in managed care settings will enable decision makers to optimize
      use of scarce healthcare dollars for improving the health and well-being of
      enrollees.

PMID- 15521162
TI  - Secondary prevention of domestic violence in HMO primary care: evaluation of
      alternative implementation strategies.
AB  - OBJECTIVES: To compare the effectiveness of 2 system-level multifaceted quality
      improvement approaches to enhancing the secondary prevention of domestic violence
      (DV) in health maintenance organization (HMO) primary care settings. STUDY
      DESIGN: A "2 new interventions" pre/post design that compared a basic
      implementation strategy using current staff levels with an augmented basic
      strategy that added a paid part-time role for medical office social workers as DV
      social change agents. METHODS: Comparison of pre-/postimplementation changes in
      clinicians' DV-related knowledge, attitudes, and self-reported practices (KAP)
      and rates of inquiry about DV with female patients. Study outcomes were measured
      in surveys of primary care clinicians and women aged 18 to 45 years who had
      recent appointments with them. RESULTS: Both strategies resulted in significant
      improvements in rates of clinician inquiry about DV and in most clinician KAP
      measures, but only 2 clinician KAP measures showed significantly greater
      improvement in the augmented strategy arm. CONCLUSIONS: Our finding that
      substantial sustainable improvement in secondary prevention of DV in primary care
      is feasible in an HMO primary care setting using existing organizational
      mechanisms and current staff levels should be encouraging to other such
      organizations considering undertaking similar initiatives. Our findings support
      viewing clinician behavior change as a process of organizational cultural change
      to be undertaken over the long term using multifaceted implementation strategies
      that employ techniques consistent with accepted theories of behavior change. They
      also emphasize the need to investigate and address the special barriers to
      screening that apparently exist in the pediatric setting.

PMID- 15521163
TI  - Does improved access to care affect utilization and costs for patients with
      chronic conditions?
AB  - OBJECTIVE: To determine whether a major improvement in access (ie, implementing
      an open access system) in a large multispecialty medical group during 2000 was
      associated with changes in utilization or costs for patients with diabetes,
      coronary heart disease (CHD), or depression. STUDY DESIGN: Multilevel regression
      analysis of health plan administrative data. PATIENTS AND METHODS: Approximately
      7000 patients with diabetes, 3800 with CHD, and 6000 with depression who received
      all of their care in this care system served as the subjects for this study.
      Utilization and costs between 1999 and 2001 (before and after implementation of
      open access) were compared for these patients. The main outcome measures were
      rates of inpatient admissions and various types of outpatient encounters as well
      as associated costs for these subjects. RESULTS: Between 1999 and 2001, total
      office visit changes were small and varied with condition, but the proportion of
      these visits made to primary care physicians increased significantly by an
      absolute 5% to 9% and primary care physician continuity increased for each
      condition. Urgent care visits also decreased significantly by an absolute 5% to
      9%, but there was no change in emergency department visits or hospital
      admissions. Total costs of care for these patients were much larger than those
      for the overall population of the medical group, but increased at a similar rate.
      CONCLUSION: A major improvement in patient access to primary care clinics was
      associated with increased use and continuity of primary care for patients with 3
      chronic conditions, but did not affect overall resource use.

PMID- 15521164
TI  - Expert skills blend when critical care meets oncology nursing.

PMID- 15521165
TI  - ONS members make a difference in health policy at local, state, and federal
      levels.

PMID- 15521166
TI  - [Role of malate dehydrogenase isoforms in the regulation of anabolic and
      catabolic processes in the colorless sulfur bacterium Beggiatoa leptomitiformis D
      402].
AB  - The functional role of tetrameric and dimeric isoforms of malate dehydrogenase in
      the carbon metabolism of the colorless sulfur bacterium Beggiatoa
      leptomitiformis, strain D-402, was studied. This strain can grow both
      lithotrophically and organotrophically. By using the inhibition analysis, the
      tetrameric isoenzyme was shown to operate in the glyoxylate cycle and the dimeric
      one was found to be involved in the TCA cycle. The dynamics of the dimeric
      isoenzyme conversion to the tetrameric isoform was found to be determined by the
      rate of thiosulfate oxidation. The regulation of the carbon metabolism in
      Beggiatoa leptomitiformis is supposed to be accomplished by means of structural
      and functional changes in the protein molecule of malate dehydrogenase.

PMID- 15521167
TI  - [The effect of temperature and pH on the growth of aerobic alkalithermophilic
      bacteria from hot springs in Buryatia].
AB  - Growth parameters (temperature and pH) were determined for collection cultures of
      aerobic heterotrophic bacteria. Analysis of the experimental data with the use of
      the Rosso model made it possible to calculate the extreme values of temperature
      and pH permissive for culture growth. The examined cultures were subdivided into
      three groups with respect to their growth temperature and pH. The first group is
      represented by the cultures with minimum, maximum, and optimal growth
      temperatures of < 20, 60-64, and 38-40 degrees C, respectively, and with the
      optimal growth pH 8.0-8.5. Bacteria of the second group are true
      alkalithermophilic organisms with a temperature optimum of 45-50 degrees C and pH
      optimum of 8.5-9.0. The third group includes a culture of a thermophilic
      alkalitolerant bacterium.

PMID- 15521168
TI  - [Role of trehalose and glycogen in the survival of aging Saccharomyces cerevisiae
      cells].
AB  - The role of the storage carbohydrates trehalose and glycogen in the survival of
      aging Saccharomyces cerevisiae cells was studied. Culture aging for one week did
      not reduce cell viability. During this period, the cells accumulated the storage
      carbohydrates and raised the activity of the glycolytic enzymes hexokinase and
      phosphofructokinase. However, further aging led to a drastic drop in cell
      viability and to a decrease in the cellular content of trehalose and glycogen and
      in the activity of hexokinase and phosphofructokinase. The possible reasons for
      these changes are discussed.

PMID- 15521169
TI  - [Germination of phytopathogenic fungi conidia].
AB  - The autoregulation of conidium germination in phytopathogenic micromycetes of the
      genera Fusarium, Botrytis, and Bipolaris was studied. It was shown that
      Trichoderma longibrachiatum was less competitive than Fusarium oxysporum after
      their simultaneous inoculation but inhibited the phytopathogen growth in the case
      of earlier introduction. In the latter case, no autoinhibition of the germination
      of F. oxysporum conidia occurred; moreover, cooperative effect was observed,
      i.e., the number of germinated F. oxysporum conidia increased with an increase in
      their density.

PMID- 15521170
TI  - [The effect of the carbohydrate components of pea roots on the enzymatic activity
      of the surface agglutinins of Rhizobium leguminosarum bv. viciae 252].
AB  - The interaction of the surface agglutinins of Rhizobium leguminosarum by. viciae
      252 with the carbohydrate components of host pea roots alters the beta
      glucosidase and proteolytic activities of the agglutinins.

PMID- 15521171
TI  - [Utilization of H2O2 as the oxygen source by bacteria of the genera Pseudomonas
      and Rhodococcus].
AB  - The growth of bacteria of the genera Pseudomonas and Rhodococcus in the presence
      of hydrogen peroxide as the sole source of oxygen was studied. The toxic effect
      of H2O2 in the concentration range of 100-200 microg/ml was shown to extend the
      lag phase by 2 to 3 days. Apart from the peroxide toxicity, the bacterial growth
      was inhibited by the toxic effect of dissolved oxygen in concentrations over 100
      microg O2/ml; in the presence of a liquid hydrocarbon phase, this effect was
      alleviated. Under decreased partial pressure of oxygen in the presence of
      hydrocarbons (12-15 vol %), the culture growth was initiated at high initial
      concentrations of H2O2 (300 microg/ml). When hydrogen peroxide concentrations
      exceeded 320 microg/ml, no growth occurred, no matter how much hydrocarbon was
      added.

PMID- 15521172
TI  - [Initial stages of 2,4,6-trinitrotoluene transformation by microorganisms].
AB  - Screening of a wide range of microorganisms (32 strains) isolated from various
      anthropogenic and natural environments and of a number of collection strains
      showed that the early stages of 2,4,6-trinitrotoluene (TNT) transformation by the
      majority of the strains studied resulted in the formation of
      hydroxylaminodinitrotoluenes (HADNTs). The levels of HADNTs were in a number of
      cases comparable to the initial TNT level. The alternative reductive attack at
      TNT through the reduction of the aromatic ring was not characteristic of most of
      the prokaryotes studied. The susceptibility to the toxic effect of TNT was
      different for gram-positive and gram-negative bacteria.

PMID- 15521173
TI  - [Mechanism of action of the extracellular bacteriolytic enzymes of Lysobacter sp.
      on gram-positive bacteria: role of the cell wall anionic polymers of the target
      bacteria].
AB  - The study of the extracellular bacteriolytic enzymes of Lysobacter sp. showed
      that they can efficiently hydrolyze the peptidoglycan of gram-positive bacteria
      provided that there is an electrostatic interaction of these enzymes with the
      cell wall anionic polymers, teichoic and teichuronic acids in particular. The
      hydrolytic action of bacteriolytic enzymes on the cell wall largely depends on
      the negative charge of teichoic and teichuronic acids, rather than on their
      chemical composition.

PMID- 15521174
TI  - [Relationship between the molecular structure of nitrogen source and the activity
      of the extracellular lectins of Lentinus edodes (Berk.) Sing [Lentinula edodes
      (Berk.) Pegler] upon submerged cultivation].
AB  - The activity of the extracellular lectins of Lentinus edodes (Berk.) Sing
      [Lentinula edodes (Berk.) Pegler] and the formation of a pigmented mycelial film
      by this fungus upon submerged cultivation in a synthetic medium were found to
      depend on the presence of some amino acids (particularly, asparagine) and Ca2+
      and Mn2+ ions in the medium. Quantum chemical calculations suggest that the
      different character of the interaction of amino acids with the aforementioned
      ions is due to differences in the hydrophobicity of the amino acids rather than
      to differences in the electron structure of the amino acid zwitterions.

PMID- 15521175
TI  - [The alkaloids of Penicillium aurantiogriseum Dierckx (1901) var. aurantiogriseum
      VKM F-1298].
AB  - The fungus Penicillium aurantiogriseum var. aurantiogriseum VKM F-1298 produces
      two benzodiazepine alkaloids (anacine and aurantine) and one diketopiperazine
      alkaloid (aurantiamine). When cultured in a submerged mode in Abe medium, the
      alkaloids are mostly secreted into the medium. The dynamics of aurantine and
      aurantiamine accumulation in the medium is characterized by the presence of a
      relatively sharp maximum in the idiophase, whereas the accumulation of anacine in
      the medium is characterized by an extended plateau and occurs concurrently with
      fungal growth.

PMID- 15521176
TI  - [Spectral properties of the green alga Trebouxia--a phycobiont of
      cryptoendolithic lichens in the high-latitude polar regions of Antarctica].
AB  - An algologically pure culture of the green alga Trebouxia, a phycobiont of
      cryptoendolithic lichens, was isolated from the sandstone samples collected in
      the high-altitude polar regions of Antarctica. The absorption and the second
      derivative absorption spectra of the acetone extract of the Antarctic phycobiont
      cells were studied in comparison with those of the Trebouxia phycobiont isolated
      recently from the Parmeliaceae lichen in the Mid-European climatic zone. The
      cells of the Antarctic phycobiont were characterized by a lower content of
      chlorophyll a and a higher ratio of chlorophyll b and carotenoids to chlorophyll
      a as compared to the Mid-European phycobiont. Furthermore, the carotenoids of the
      Antarctic phycobiont were more diverse. The low-temperature fluorescence spectra
      of the Antarctic phycobiont were characterized by an increased intensity of the
      short-wavelength fluorescence peak of chlorophyll a and a diminished intensity of
      fluorescence in the long-wavelength spectral region.

PMID- 15521177
TI  - [A comparative analysis of the ice nucleation activity of pseudomonad cells and
      lipopolysaccharides].
AB  - The paper deals with the study of the ice nucleation activity of the cells,
      extracellular lipopolysaccharides (ELPSs), lipopolysaccharides (LPSs), and their
      structural components (lipid A, core oligosaccharide, and O-specific
      polysaccharide) of Pseudomonas fluorescens, P. syringae, P.fragi, and P.
      pseudoalcaligenes. The aqueous suspensions of the intact cells of P. syringae IMV
      1951 and IMV 185 began to freeze at -1 and -4 degrees C, respectively. This
      suggests that these cells possess ice nucleation activity. The aqueous cell
      suspensions of two other strains, P. fluorescens IMV 1433 and IMV 2125, began to
      freeze at lower temperatures than did distilled water (-9 degrees C), which
      suggests that the cells of these strains possess antifreeze activity. The ice
      nucleation activity of the bacterial strains studied did not show any correlation
      with their taxonomic status. The ice nucleation activity of ELPSs depended little
      on their concentration (within a concentration range of 0.2-0.4%). In most cases,
      the ice nucleation activity of ELPSs, LPSs, and their structural components
      differed from that of the intact cells from which these biopolymers were
      obtained. This may indicate that the biopolymers under study play a role in ice
      nucleation, but this role is not crucial. The relationship between the structure
      of LPSs and their effect on ice nucleation is discussed.

PMID- 15521178
TI  - [Correlation between the cellular content of mobile water and the viability of
      lyophilized yeast cells].
AB  - Spin-echo NMR studies showed that lyophilized yeast cells contain isolated mobile
      water (IMW), whose content varied from 0.25% (of the dry weight of cells) in the
      lyophilized exponential-phase yeast cells to 3.8% in the lyophilized lag-phase
      and stationary-phase yeast cells. The viability rate of yeast cells varied from
      20% in the lyophilized preparation of exponential-phase cells to 86% in the
      lyophilized preparation of early-stationary-phase cells. In the lyophilized
      preparation of yeast cells grown in a chemostat mode at a constant specific rate,
      the content of IMW depended on the growth-limiting factor, being minimal in the
      case of growth limitation by carbon source. In the latter case, the viability
      rate of cells was also minimal. The data obtained show that there is a
      correlation between the IMW content and the viability rate of yeast cells in
      lyophilized preparations.

PMID- 15521179
TI  - [Ultrastructure of resting cells of some non-spore-forming bacteria].
AB  - Using electron microscopy (ultrathin sections and freeze-fractures), we
      investigated the ultrastructure of the resting cells formed in the cultures of
      Micrococcus luteus, Arthrobacter globiformis, and Pseudomonas aurantiaca under
      conditions of prolonged incubation (up to 9 months). These resting cells included
      cyst-like forms that were characterized by complex cell structure and the
      following ultrastructural properties: (i) a thickened or multiprofiled cell wall
      (CW), typically made up of a layer of the preexisting CW and one to three de novo
      synthesized murein layers; (ii) a thick, structurally differentiated capsule;
      (iii) presence of large intramembrane particles (d = 180-270 A), occurring both
      on the PF and EF sides of the membrane fractures of M. luteus and A. globiformis;
      (iv) a peculiar structure of the cytoplasm, which was either fine-grained or
      lumpy (coarse-grained) in different parts of the cell population; and (v) a
      condensed nucleoid. Intense formation of cyst-like cells occurred in aged (2- to
      9-month-old) bacterial cultures grown on diluted complex media or on nitrogen-,
      carbon-, and phosphorus-limited synthetic media, as well as in suspensions of
      cells incubated in media with sodium silicate. The general morphological
      properties, ultrastructural organization, and physiological features of cyst-like
      cells formed during the developmental cycle suggest that constitutive dormancy is
      characteristic of non-spore-forming bacteria.

PMID- 15521180
TI  - [New thermophilic methanotrophs of the genus Methylocaldum].
AB  - Two pure cultures of obligate methanotrophs, strains H-11 and 0-12, growing in
      the temperature range from 30 to 61 degrees C with an optimum at 55 degrees C
      were isolated from samples of silage and manure. Based on the results of analysis
      of the 16S rRNA genes, membrane-bound methane monooxygenase, and phenotypic
      properties, the isolates were assigned to the genus Methylocaldum. Significant
      temperature-dependent variations in morphology and phospholipid and fatty acid
      composition were revealed. Both strains assimilated methane carbon via the
      ribulose monophosphate, serine, and ribulose bisphosphate pathways. The activity
      of hexulose phosphate synthase was independent of the cultivation temperature;
      however, the activities of hydroxypyruvate reductase and ribulose bisphosphate
      carboxylase were higher in cells grown at 55 degrees C that in cells grown at 37
      degrees C, indicating the important roles of the serine and ribulose bisphosphate
      pathways in the thermoadaptation of the strains under study. NH4+ assimilation
      occurred through reductive amination of alpha-ketoglutarate and via the glutamate
      cycle. The relationship between the physiological-biochemical peculiarities of
      the isolates and their thermophilic nature is discussed.

PMID- 15521181
TI  - [The biogeochemical cycle of methane in the coastal zone and littoral of the
      Kandalaksha Bay of the White Sea].
AB  - Microbiological and biogeochemical investigations of the processes of methane
      production (MP) and methane oxidation (MO) in the coastal waters and littoral of
      the Kandalaksha Bay of the White Sea were carried out. The studies were conducted
      in the coastal zones and in the water areas of the Kandalaksha Preserve, Moscow
      University White Sea Biological Station, and Zoological Institute (RAS)
      Biological Station in August, 1999, 2000, and 2001 and in March, 2001. The rate
      of CO2 assimilation in the shallow and littoral sediments was 35-27800 microg
      C/(dm3 day) in summer and 32.8-88.9 microg C/(dm3 day) in winter. The maximal
      rates of MP were observed in the littoral sediments in the zone of macrophyte
      decomposition, in local depressions, and in the estuary of a freshwater creak (up
      to 113 microl/(dm3 day)). The maximal level of MO was observed in the shallow
      estuarine sediments (up to 2450 microl/(dm3 day)). During the winter season, at
      the temperature of -0.5 to 0.5 degrees C, the MP rate in the littoral sediments
      was 0.02-0.3 microl/(dm3 day), while MO rate was 0.06-0.7 microl/(dm3 day). The
      isotopic data obtained indicate that the C(org) of the mats and of the upper
      sediment layers is enriched with the heavy 13C isotope by 1-4 per thousand as
      compared to the C(org) of the suspension, comprised on 33.5-34.3% of
      phytoplankton. A striking difference was found between the levels of methane
      emission by the typical littoral microlanscapes. In fine sediments, the average
      emission was 675 microl CH4/(m2 day), in the stormy discharge stretch sediments
      it was 1670 microl CH4/(m2 day), and under the stones and in silted pits, 1370
      microl CH4/(m2 day). The calculation performed with consideration of the
      microlandscape areas with a high production allowed the CH4 production of 1 km2
      of the littoral to be estimated as 192-300 1 CH4/(km2 day).

PMID- 15521182
TI  - [High-temperature microbial sulfate reduction can be accompanied by magnetite
      formation].
AB  - The hyperthermophilic sulfate-reducing archaeon Archaeoglobus fulgidus was found
      to be capable of lithoautotrophic growth on medium containing molecular hydrogen,
      sulfate, and amorphous Fe(III) oxide. During the growth of this microorganism,
      amorphous Fe(III) oxide was transformed into black strongly magnetic sediment
      rich in magnetite, as shown by Mossbauer studies. Experiments involving
      inhibition of microbial sulfate reduction and abiotic controls revealed that
      magnetite production resulted from chemical reactions proceeding at elevated
      temperatures (83 degrees C) between molecular hydrogen, amorphous Fe(III) oxide,
      and sulfide formed enzymatically in the course of dissimilatory sulfate
      reduction. It follows that magnetite production in this system can be
      characterized as biologically mediated mineralization. This is the first report
      of magnetite formation as a result of activity of sulfate-reducing
      microorganisms.

PMID- 15521183
TI  - [Community structure of yeast fungi in forest biogeocenoses].
AB  - The results of longstanding studies of yeasts inhabiting soil, plant surface, and
      plant residues in typical subboreal forests of the European part of Russia are
      summarized. The abundance and species diversity of yeast communities in the array
      of substrates corresponding to succession stages in plant residues decomposition
      are shown to steadily decline. Each stage is characterized by its specific set of
      dominating species. The yeast diversity in forest biogeocenoses is shown to
      surpass that in other geographic zones. This manifests itself in a greater number
      of species occurring in similar arrays of substrates, in the absence of
      conspicuous dominants on the biogeocenotic level, and in a higher differentiation
      of the yeast population with respect to its habitat type. The forest yeast
      populations are also characterized by high diversity of yeasts of ascomycetous
      affinity and of the anamorphic stages of Taphrinales and Tremellales, as well as
      by the presence of typical pedobiont species (except Lipomyces spp.).

PMID- 15521184
TI  - [The ability of saprotrophic bacteria isolated from natural habitats to lyse
      yeasts].
AB  - More than 600 bacterial strains isolated from different horizons of steppe
      biogeocenoses and zoogenous loci (diplopod intestines and feces) were tested for
      the ability to lyse yeast cell walls. About half of the strains that were
      isolated from biotopes with active degradation of plant debris (steppe litters
      and diplopod intestines and feces) were found to possess yeast-lytic activity.
      Most of the yeast-lytic strains belonged to the genera Streptomyces,
      Promicromonospora, Oerskovia, and Agromyces. The yeast-lytic activity of
      actinobacteria from the genera Agromyces, Mycobacterium, and Micrococcus has not
      previously been reported.

PMID- 15521185
TI  - [Spectral properties of ancient green algae from buried ice in the high-latitude
      polar regions of Antarctica].

PMID- 15521186
TI  - [Inhibition of the growth and methane consumption in Methylocapsa acidiphila by
      mineral salts].

PMID- 15521187
TI  - Lipoprotein oxidation products and arteriosclerosis: theory and methods with
      applicability to the clinical chemistry laboratory.

PMID- 15521188
TI  - Measurement of matrix metalloproteinases (MMPs) and tissue inhibitors of
      metalloproteinases (TIMP) in blood and urine: potential clinical applications.

PMID- 15521189
TI  - Molecular method to quantitatively detect micrometastases and its clinical
      significance in gastrointestinal malignancies.

PMID- 15521190
TI  - Zymographic evaluation of plasminogen activators and plasminogen activator
      inhibitors.

PMID- 15521191
TI  - Estrogen metabolites, conjugates, and DNA adducts: possible biomarkers for risk
      of breast, prostate, and other human cancers.

PMID- 15521192
TI  - Organophosphates/nerve agent poisoning: mechanism of action, diagnosis,
      prophylaxis, and treatment.
AB  - OP/nerve agents are still considered as important chemicals acting on living
      organisms and are widely used. They are characterized according to their action
      as compounds influencing cholinergic nerve transmission via inhibition of AChE.
      Modeling of this action and extrapolation of experimental data from animals to
      humans is more possible for highly toxic agents than for the OP. The symptoms of
      intoxication comprise nicotinic, muscarinic, and central symptoms; for some
      OP/nerve agents, a delayed neurotoxicity is observed. Cholinesterases (AChE and
      BuChE) are characterized as the main enzymes involved in the toxic effect of
      these compounds, including molecular forms. The activity of both enzymes (and
      molecular forms) is influenced by inhibitors (reversible, irreversible, and
      allosteric) and other factors, such as pathological states. There are different
      methods for cholinesterase determination; however, the most frequent is the
      method based on the hydrolysis of thiocholine esters and subsequent detection of
      free SH-group of the released thiocholine. The diagnosis of OP/nerve agent
      poisoning is based on anamnesis, the clinical status of the intoxicated organism,
      and on cholinesterase determination in the blood. For nerve agent intoxication,
      AChE in the red blood cell is more diagnostically important than BuChE activity
      in the plasma. This enzyme is a good diagnostic marker for intoxication with OP
      pesticides. Some other biochemical examinations are recommended, especially
      arterial blood gas, blood pH, minerals, and some other specialized parameters
      usually not available in all clinical laboratories. These special examinations
      are important for prognosis of the intoxication, for effective treatment, and for
      retrospective analysis of the agent used for exposure. Some principles of
      prophylaxis against OP/nerve agent poisoning comprising the administration of
      reversible cholinesterase inhibitors such as pyridostigmine (alone or in
      combination with other drugs), scavengers such as preparations of
      cholinesterases, some therapeutic drugs, and possible combinations are given.
      Basic principles of the treatment of nerve agent OP poisoning are described. They
      are based on the administration of anticholinergics (mostly atropine but some
      other anticholinergics can be recommended) as a symptomatic treatment,
      cholinesterase reactivators as a causal treatment (different types but without a
      universal reactivator against all OP/nerve agents) as the first aid and medical
      treatment, and anticonvulsants, preferably diazepam though some other effective
      benzodiazepines are available. New drugs for the treatment are under experimental
      study based on new approaches to the mechanism of action. Future trends in the
      complex research of these compounds, which is important not only for the
      treatment of intoxication but also for the quantitative and qualitative increase
      of our knowledge of toxicology, neurochemistry, neuropharmacology, clinical
      biochemistry, and analytical chemistry in general, are characterized.

PMID- 15521193
TI  - The potential of protein-detecting microarrays for clinical diagnostics.

PMID- 15521194
TI  - Clinical laboratory implications of single living cell mRNA analysis.

PMID- 15521195
TI  - The contribution of exo- as well as endogenous substances to the total
      antioxidant capacity.

PMID- 15521196
TI  - [Are blood lipids a risk factor for drug addicts? A commentary to an article
      "Serum lipids in drug addicts" by Wilczek, H., Ceska, R., Zlatohlavek, L].

PMID- 15521197
TI  - [Recurrent varices].

PMID- 15521198
TI  - [Can be incidence of peritonitis associated with peritoneal dialysis further
      decreased?].

PMID- 15521199
TI  - [Several diagnostic remarks to a casuistry of fibrillar glomerulonephritis--a
      morphologists' opinion].

PMID- 15521200
TI  - [Serum lipids in drug addicts].
AB  - The background and aim is to study profile of serum lipids in drug addicts using
      heroin. METHODS AND RESULTS: The study involved 107 drug addicts using heroin (83
      men and 24 women). Mean age was 29.3 years (variation 20-47 years). Mean time of
      using heroin was 6.5 years. Serum lipids (total cholesterol, HDL-cholesterol,
      triacylglycerol) were measured using enzyme methods. LDL-cholesterol and Body
      Mass Index (BMI) were calculated. All parameters were significantly decreased
      (mean levels of total cholesterol 4.31, triacylglycerol 1.29, HDL-cholesterol
      1.08 and LDL-cholesterol 2.70 mmol/l). Levels of HDL-cholesterol under 1.0 mmol/l
      were found in 32%. Statistical measurments were performed by t-test and results
      compared with control group. CONCLUSIONS: Levels of HDL-cholesterol lower than
      1.0 mmol/l (32%) are of importance and patients must be further controlled.

PMID- 15521201
TI  - [Recurrence of varices in lower extremities].
AB  - Authors have done a retrospective analysis of 94 lower extremities in 88 patients
      examined from 1996 to 2002 for recurrence of varices in lower extremities. The
      goal was to find out the most frequent causes of recurrence of varices in lower
      extremities in patients with history of varices surgery referred to venous
      guidance clinic because of another onset of varices in lower extreminites or
      clinical signs of chronic venous insufficiency. Reflux was proved in 78 lower
      extremities from the total number of 94 (83%) in our sample. Isolated reflux was
      discovered in 59 extremities in saphenofemoral junction (39 extremities), in
      saphenopopliteal junction (14 extreminies), and in perforators (6 extremities).
      Combined reflux detected simultaneously in two or three places (SFJ, SPJ,
      perforators) was found in 19 extremities. In 11 cases the reflux was proved in
      two places and in 8 cases even in 3 places simultaneously. The main cause of
      recurrence of varices in lower extremities in our sample was reflux especially in
      saphenofemoral junction and saphenopopliteal junction. Reflux in perforators was
      usually accompanied with saphenofemoral and/or saphenopopliteal junctions
      incompetence. Isolated reflux in perforators was found very rarely (6.4%). The
      cause of varices recurrence was not disclosed in 17% of cases.

PMID- 15521202
TI  - [Use of assessment of aggregation of thrombocytes induced by cationic propyl
      gallate to estimate recurrence of cardiovascular complications].
AB  - INTRODUCTION: Recently resistance to an acetylsalicylic acid (ASA) administration
      has been a frequently mentioned problem. However, to identify ASA nonresponsive
      patients (ASA resistance) is difficult and common examination procedures can
      contain important preanalytic, analytic and postanalytic mistakes. Recently a
      possibility to use aggregometry after induction with cationic propyl gallate
      (CPG) has been discussed in this context; it's a robust, highly sensitive, and
      specific method for ASA resistance estimates. We asked ourselves following
      questions during our work: GOAL: a) Experience patients with acute coronary
      syndrome (ACS) ASA resistance more often than healthy volunteers?; b) Are
      aggregation values in both patients with different metabolic homeostasis
      disorders and patients with risk factors for atherosclerotic complications
      different?; c) Change results of measured aggregation induced by CPG in patients
      treated with identical ASA therapy during a several years long monitoring;
      respectively are patients assessed differently during the monitoring?; d) Is it
      possible to use one-shot aggregation assessment following CPG to estimate ASA
      resistance or is it necessary to repeat the examinations?; e) Is recurrence of
      ACS complications more frequent during two years of monitoring of patients with
      ACS history resistant to 100 mg doses of ASA per day? METHOD: 103 patients of an
      average age 69 were assessed. All of them suffered from ACS without ST segment
      elevations and were treated conservatively; in addition to it all of them were
      treated with 100 mg ASA/day. They were assessed at the onset of ACS and after 3,
      12 and 24 months. The examination consisted of taking patient history, clinical
      examination, BMI determination, laboratory test for cholesterol, HDL, LDL,
      triacylglycerols, and glucose, and of an aggregation of thrombocytes assessment
      under standard conditions (spontaneous and after CPG induction). RESULTS AND
      CONCLUSION: a) ASA resistance is more frequent in patients with ACS compared to
      healthy volunteers (45% to 6%, p < 0.001). b) Patients with type II DM, smokers,
      patients with low HDL cholesterol levels or high triacylglycerols levels are ASA
      resistant more often (< 0.05). c) Results of measured aggregation of thrombocytes
      don't change during administration of the identical dose of 100 mg ASA/day during
      2 years of monitoring. Respondents usually are assessed identically during
      monitoring (responsive/ASA nonresponsive). d) ASA resistance can be estimated
      from one-shot aggregation assessment following induction with CPG. e) Two years
      after diagnosing the ASA resistance a percentage of cardiovascular complications
      recurrence is higher in patients with history of ACS (p < 0.001). One-shot
      assessments of the CPG induced thrombocytes aggregation and the spontaneous
      aggregation are sensitive in 81% of patients with ACS history and specific in
      100% of patients at risk of recurrence of cardiovascular complications. If these
      results are confirmed it could lead to a change in interventions in patients with
      ASA resistance proved by this method.

PMID- 15521203
TI  - [Deferral of coronary intervention based on measurement of myocardial fractional
      flow reserve].
AB  - BACKGROUND: Myocardial fractional flow reserve (FFR) is a useful method in
      assessment of functional significance of coronary stenosis. Deferral of
      intervention of angiographically intermediate lesion based on FFR measurement is
      safe in selected patient population as previously described. The aim of the study
      was to assess mid-term results after deferring coronary intervention of
      intermediate lesion in a non-selected patient population with no respect to the
      extent of coronary artery disease and to the results of stress tests if
      performed. METHODS: A coronary intervention of angiographically intermediate
      lesion (40 - 70% according to QCA) was deferred in a group of 50 consecutive
      patients (33 men, mean age 60.8 +/- 10.2 y.) on the basis of FFR > or = 0.75
      (mean FFR 0.89 +/- 0.06). FFR was measured in 62 lesions (mean stenosis diameter
      55 +/- 7%, left anterior descending 34 lesions, circumflex artery 13 lesions,
      right coronary artery 15 lesions). One-vessel disease was presented in 14 pts
      (28%), 36 pts (72%) presented with multivessel disease (two-vessel disease in 27
      pts - 54% and three-vessel disease in 9 pts - 18%). Stress test was positive in
      15 pts, in 1 pts. negative, and in 3 pts. non-diagnostic. All-cause mortality,
      cardiac mortality, non-fatal myocardial infarction (MI) and ischemia driven
      target vessel revascularization (TLR) were recorded during follow-up. Severity of
      angina pectoris (CCS classification) and a need for antianginal treatment (beta
      blockers, nitrates, calcium channel blockers) at the baseline and at the end of
      clinical follow-up was recorded. RESULTS: Follow-up was completed in 49 patients
      (98%). Mean time of follow-up is 15.4 +/- 2 months (range 12 - 22 months, median
      15 months), two patients died (4 %)--one from colon cancer, the other patient
      died from lung cancer, there was not any cardiac death recorded, two patients
      (4%) had target vessel revascularization. Estimated 22 months event-free (all
      cause death, MI, TLR) survival was (mean +/- SEM) 86 +/- 7%. There was a
      significant difference in symptom severity--mean grade of angina pectoris at
      baseline was 1.8 +/- 1.3, at follow-up 1.1 +/- 1.0 (p < 0.05). There was not
      difference in use of antianginal drugs was same at baseline and at follow-up (1.7
      +/- 0.8 vs. 1.7 +/- 0.7). Thirty-five patients (71%) were treated by statins.
      CONCLUSIONS: Deferring of coronary interventions of intermediate stenosis based
      on FFR measurement is safe in a mid-term follow-up. Despite of the same intensity
      of antianginal treatment there was a significant decrease in symptom severity.

PMID- 15521204
TI  - [Families at risk of colon cancer II. Hereditary nonpolyposis colorectal
      carcinoma].
AB  - Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant
      inherited disease characterised by almost inevitable development of colorectal
      carcinoma and/or endometrium and other defined malignancies in affected
      individuals. HNPCC is caused by a germline mutation in a mismatch repair genes
      (MMR). The purpose of this review is to summarize current knowledge regarding
      HNPCC with the focus on recent data on genetic testing, surveillance guidelines
      and therapy. Available medical databases were searched from 1998 to May 2003
      using the keywords "hereditary nonpolyposis colorectal cancer", followed by
      further search for particular issues. Additional articles were identified through
      the reference sections of retrieved articles and from personal archive of
      authors. Approximately 200 papers on HNPCC are published yearly. The major
      progress in recent research of HNPCC has been made in the area of genetic testing
      and clinical surveillance. Current guidelines recommend identification of
      microsatelite instability in a tumour of affected family member followed by
      germline testing in this person. Once mutation in particular MMR gene is found,
      screening of all at risk members is recommended. Alternative approach suggests
      direct germline testing in unaffected family member provided that the testing in
      affected member is not possible. Annual colonoscopy examinations starting at 20
      25 years and gyneacological examination starting at 30-35 years are recommended
      in all family members at risk. Recent advances in genetic tests and surveillance
      strategies result in decreased mortality of HNPCC patient.

PMID- 15521205
TI  - [Hypothyroidism and heart failure].
AB  - Effects of thyroid gland hormones on cardiovascular system have been known for
      many years. Thyroid gland hormones deficiency is connected with a range of
      metabolic and hemodynamic changes which can contribute to a genesis of heart
      failure. Recent works refer to an importance of connection of thyroid gland
      hormones metabolism with heart insufficiency pathophysiology. That is especially
      a syndrome of a low trijodthyronin level marked as euthyroid sick syndrome which
      is significantly more frequent in patients with chronic heart failure compared to
      a population of healthy individuals. Recent clinical works proved that treatment
      administration of thyroid gland hormones to patients with heart failure is
      connected with favourable hemodynamic changes and increased working capacity if
      the treatment is well tolerated.

PMID- 15521206
TI  - [The latest trends in the treatment peritonitis of the patients on peritoneal
      dialysis].
AB  - Peritonitis is still one of the major complications ambulatory peritoneal
      dialysis (CAPD). The initial empiric therapy for peritonitis should be effective
      against most grampositive organisms as well as gramnegative organisms.
      Intraperitoneal administration antibiotics has the advantage of a high
      concentration of the antibiotics at the site of infection. The treatment should
      provide broad coverage of all organisms, without side-effects or risk for the
      patient and should not provoke the emergence of resistant germs. The present
      guidelines of the ad hoc advisory committee are of great value in this regard.
      The ISPD guidelines for treatment of peritonitis recommended an empirical therapy
      based on the association of a first-generation cephalosporin with an
      aminoglycoside or ceftazidime.

PMID- 15521207
TI  - [Fibrillary glomerulonephritis--a rare cause of nephrotic syndrome].
AB  - Fibrillary glomerulonephritis (FGN) is a rarely diagnosed disease with clinical
      manifestations such as proteinuria, microscopic hematuria, nephrotic syndrome or
      decreased kidney function. Around one half of patients develop chronic renal
      failure in the course of several years. The diagnosis of fibrillary
      glomerulonephritis is to be established only basing on the results of renal
      biopsy. Pathognomonic is the electron-microscopic examination, evidencing
      fibrillar deposits in mesangium and in basal membranes of glomeruli. Fibrils are
      similar to those seen at amyloidosis, however, with larger diameter, non-linear
      deposition and do not stain with Congo red or thioflavin T. Immunofluorescency
      test usually shows the presence of IgG, namely the subclasses IgG4, C3 and kappa
      and lambda of light immunoglobulin chains. The presented case report describes
      clinical and laboratory findings at a patient suffering from nephrotic syndrome.
      Results of renal biopsy and detailed histological examinations concluded the
      diagnosis as fibrillary glomerulonephritis. The patient was treated with a
      combination of prednisone (1 mg/kg/24 hrs) with cyclophosphamide (2 mg/kg/24 hrs)
      for six months. This led to a decrease of proteinuria from the initial value of
      5.38 g/24 hours to 1.88 g/24 hours, as well as to a partial remission of
      nephritic syndrome. Glomerular filtration, evaluated using endogenous creatinine
      clearance, remained within limits of normal values throughout the follow-up, with
      the value of 2.6 ml/s after the treatment.

PMID- 15521208
TI  - [Case description of the abnormally big pseudoaneurysm in a patient after
      myocardial infarction].
AB  - Authors present a case of a 72 years old woman with an abnormally big left
      ventricular pseudoaneurysm as a consequence of a rupture of the left ventricular
      wall during myocardial infarction. Pseudoaneurysm threatens its carrier with both
      sudden death as a result of the rupture and a progressing heart failure. The
      patient mentioned has undergone an infero-lateral myocardial infarction
      complicated with beginning cardiogenic shock in July 2001. Based on
      coronarography examination which proved only peripheral stenoses in coronary bed
      a conservative procedure was indicated. In June 2002 the patient was admitted to
      a hospital for progressive dyspnoea, nonspecific chest and epigastric pain, and
      dyspeptic complaints. Transtoracal echocardiography examination proved a large
      pseudoaneurysm coming from periapical bottom wall of the left ventricle.
      Diagnosis was further confirmed and specified by ventriculography and the patient
      was indicated for surgery. Authors present a range of clinical signs of
      pseudoaneurysm, an approach to an examination, differential diagnostics and
      treatment procedure in patients with this unusual complication.

PMID- 15521209
TI  - [Czech internists--writers].

PMID- 15521210
TI  - [Ezetimib--a new possibility for combined therapy in hypercholesterolemia].

PMID- 15521211
TI  - Conjectures on knowledge "Under the Tuscan Sun".

PMID- 15521212
TI  - What's in the pipeline about bladder reconstructive surgery? Some remarks on the
      state of the art.
AB  - The fusion of engineering with cell biology and advances in biomaterials may lead
      to de novo construction of implantable organs. Engineering of neobladder from
      autologous urothelial and smooth muscle cells cultured on biocompatible, either
      synthetic or naturally-derived substrates, is now feasible in preclinical studies
      and may have clinical applicability in the near future. The development of a
      bioartificial bladder would warrant the prevention of both the metabolic and
      neoplastic shortcomings of the intestinal neobladder. Two tissue-engineering
      techniques for bladder reconstruction have been tested on animals: 1) the in vivo
      technique involves the use of naturally-derived biomaterials for functional
      native bladder regeneration 2) the in vitro technique involves the establishment
      of autologous urothelial and smooth muscle cell culture from the host's urinary
      tract, after which the cells are seeded on the biodegradable matrix-scaffold to
      create a composite graft that is implanted into the same host for complete
      histotectonic regeneration. Waiting for the creation of a complete tissue
      engineered bladder with a trigone-shaped base, we suggest, in surgical oncology
      after radical cystectomy, the realization of conduit or continent pouch using
      tissue-engineered material.

PMID- 15521213
TI  - The role of epithelial to mesenchymal transdifferentiation in end-stage renal
      disease.

PMID- 15521214
TI  - Serum tonicity, extracellular volume and clinical manifestations in symptomatic
      dialysis-associated hyperglycemia treated only with insulin.
AB  - The absence of osmotic diuresis modifies the effects of hyperglycemia on body
      fluids in patients with advanced renal failure. To determine the relationship
      between clinical manifestations and abnormalities in tonicity and extracellular
      volume in such patients, we analyzed 43 episodes of severe dialysis-associated
      hyperglycemia (serum glucose exceeding 600 mg/dL) treated only with insulin. The
      main manifestations were dyspnea in 22 cases (pulmonary edema in 19), nausea and
      vomiting in 15, coma in 13 and seizures in 3, while 5 patients had no symptoms.
      Treatment with insulin resulted in a decrease in serum glucose value from 913 +/-
      197 mg/dL to 170 +/- 78 mg/dL, an increase in serum sodium level from 125 +/- 5
      to 136 +/- 5 mmol/L, and a fall in calculated serum tonicity value from 300 +/-
      13 to 282 +/- 11 mmol/kg (all at p < 0.001). The ratio of the change in serum
      sodium level over change in serum glucose concentration was -1.50 +/- 0.22 mmol/L
      per 100 mg/dL. The percent increase in extracellular volume secondary to
      hyperglycemia developing from the prior euglycemic state and calculated from
      changes in serum sodium and chloride concentrations, was 10.9% +/- 4.6% (1.5% +/-
      0.6% per 100 mg/dL increase in serum glucose level). All clinical manifestations
      dissipated after correction of hyperglycemia in 42 patients. One woman developed
      during treatment a fatal myocardial infarction. Dialysis patients with severe
      hyperglycemia may develop symptoms as a result of hypertonicity and extracellular
      expansion. Insulin alone may be sufficient treatment for these symptoms. The
      changes in serum tonicity and electrolytes during treatment are consistent with
      theoretical predictions.

PMID- 15521215
TI  - Cardiac calcium evaluation in hemodialysis patients with multisection spiral
      computed tomography.
AB  - AIM: The aim of this study is cardiac calcium content evaluation in hemodialysis
      patients by a new technique, based on ultrafast multisection CT (MTC). METHODS:
      The study was carried out on 30 HD patients, 14 F and 16 M, average age 57.7 +/-
      13.9 years, average HD age 57.3 +/- 47.4 months. The intact PTH levels were 625.4
      +/- 571 pg/mL. Serum calcium, phosphate and CaxP product were 9.75 +/- 0.84
      mg/mL, 6.21 +/- 1.01 mg/dL and 60.2 +/- 10.7 mg2/dL2, respectively. RESULTS: The
      values obtained with the MTC technique were reported in terms of Agatson scores.
      Score values frankly in the pathologic range (>100) were found in 24 patients
      (80%). Correlation analysis has shown positive and significant correlation
      coefficients of the score with patients' age (p = 0.003), serum calcium (p =
      0.012), CaxP (p = 0.015), iPTH (p = 0.049), and borderline, to HD age (p = 0.
      06). CONCLUSION: Risk factors for cardiac calcification are mainly age, degree of
      hyperparathyroidism, increased CaxP and serum calcium levels. A control of
      calcium phosphate parameters in hemodialysis patients seems to be mandatory to
      avoid increased severity of coronary artery disease.

PMID- 15521216
TI  - Natural killer cell activity unaffected by ozonated autohemotherapy in patients
      with end-stage renal disease on maintenance renal replacement therapy.
AB  - Ozonotherapy is a complementary medical approach in the treatment of resistant
      infections, immune deficiency syndromes, orthopedic pathologies and vascular
      diseases. The criticism of this method is associated with potentially harmful
      effects of ozone on cells. The aim of this study was to investigate the influence
      of ozonated autohemotherapy (O3-AHT) on the cellular response of the immunologic
      system represented by cytotoxic activity of natural killer cells. 12 hemodialyzed
      patients (8 M, 4 F) aged 64.8 +/- 7.6 years with peripheral arterial disease as
      the main reason for the treatment with O3-AHT were examined in a prospective,
      placebo controlled, single blind study. They received 9 sessions of
      autohemotherapy without ozone exposure as a placebo-control and subsequent 9
      sessions of O3-AHT. The procedures were performed 3 times a week, just before
      hemodialysis session. Ozone-oxygen gas mixture with ozone concentration of 50
      microg/ml produced by ozone generator (ATO3, KrioMetrum, Poland) was used during
      O3-AHT Natural killer cell activity was measured using lactate dehydrogenase
      release assay There was no statistical difference between natural killer cell
      activity (%) at the baseline (16.78 +/- 8.07), after nine sessions of control
      autohemotherapy (15.98 +/- 6.67), and after nine sessions of O3-AHT (18.26 +/-
      8.82). In conclusion, our findings showed that O3-AHT in a dose of 50 mg/mL does
      not have any significant influence on natural killer cell function in
      hemodialyzed patients.

PMID- 15521217
TI  - Right atrial thrombi complicating use of central venous catheters in
      hemodialysis.
AB  - BACKGROUND: There has been an increase in the use of central venous catheters for
      temporary hemodialysis access. In this report, we describe a case series of 12
      patients on hemodialysis who developed intracardiac clots associated with the use
      of central venous catheters, their outcomes and review the literature on this
      syndrome. METHODS: Retrospective, single-center case series of 12 patients with
      right atrial thrombi associated with central venous catheter use for dialysis
      vascular access. These patients were treated between June 1, 2001 and June 30th
      2002 at the three University of Rochester affiliated dialysis clinics. The
      medical records of these patients were reviewed to obtain information concerning
      demographics, dialysis history, dates of catheter insertion, catheter
      complications, identification and dimensions of intracardiac thrombi,
      echocardiographic data, and outcome of anticoagulant therapy. RESULTS: Right
      heart thrombi were identified in 12 patients in our hemodialysis population over
      the study interval. Anticoagulation for 6 months led to clot resolution in more
      than 50% of our patients. Bacteremia recurred in 6 patients (50%), in spite of
      catheter replacement. There was zero mortality related to presence of clots in
      the short term. One patient with non-bacteremic right atrial thrombus suffered
      sudden cardiac arrest, but was successfully resuscitated. CONCLUSION: Right
      atrial thrombi may occur in hemodialysis patients who use central venous
      catheters for dialysis access. These clots are frequently found in the right
      atrium or right atrial-superior vena caval junction. Ten of 12 patients (83%),
      had catheter-associated bacteremia, but the precise relationship between
      bacteremia and intracardiac clots is unclear. Chronic anticoagulation for 6
      months lead to resolution of these clots in more than 50% of patients in our
      series.

PMID- 15521218
TI  - Cavitation phenomenon in monoleaflet mechanical heart valves with
      electrohydraulic total artificial heart.
AB  - Recently, cavitation on the surface of mechanical heart valves has been studied
      as a cause of fractures occurring in implanted mechanical heart valves. In this
      study, to investigate the mechanism of cavitation bubbles associated with
      monoleaflet mitral valves in an electrohydraulic total artificial heart (EHTAH),
      and to select the best valves for our EHTAH system, we measured three parameters.
      First, an image was created of the cavitation bubbles using a high-speed camera.
      Second, pressure drop in the vicinity of the valve surface was measured using
      mini pressure sensor. Then, the closing of the valve was observed using a Laser
      displacement sensor. Most of the cavitation bubbles in the Medtronic Hall valve
      were observed at the edge of the valve stop. With the Omnicarbon valve, the
      cavitation bubbles were observed at the edge of the valve and on the inner side
      of the leaflet. On the other hand, cavitation bubbles were observed only on the
      inner side of the leaflet in Bjork-Shiley valve. Cavitation bubbles concentrated
      on the edge of the valve stop; the major cause of these cavitation bubbles was
      determined to be the squeeze flow. The formation of cavitation bubbles depended
      on the valve closing velocity and the valve leaflet geometry. From a viewpoint of
      squeeze flow, a low closing velocity and a small size of the valve stop could
      minimize cavitation.

PMID- 15521219
TI  - Robust motor speed control under time varying loads in moving actuator type
      artificial heart (AnyHeart).
AB  - The Moving Actuator type artificial heart(AnyHeart) as well as many other
      artificial hearts uses a motor as its power source. For controllability of
      control parameters such as pump rate, pump output, blood pressure profile and
      flow form, the precise motor speed control is important. However, because the
      implantable device has limited carrying capacity of hardware components in size
      and number, applying diverse motor control methods are not possible. In addition,
      the existing PI (Proportional-Integral) motor controller does not show
      satisfactory performance. A new controller that is sufficiently robust for the
      changes of load and physical system parameters has been designed and tested. The
      robust speed controller is based on the sliding mode control method that is
      applicable to a system of which the ranges of uncertainty in physical parameters
      are known. In a mock circulation system test, the actual speed showed good
      tracking characteristics in respect to the reference speed. Fast follow-up
      characteristics were also observed under high afterload and speed conditions. The
      speed error, current and power consumption were reduced by about 40%. The
      proposed control technique overcomes the limitations of the PI controller, and
      makes important improvements in both performance and stability.

PMID- 15521220
TI  - Natural and synthetic polyesters for musculoskeletal tissue repair: experimental
      in vitro and in vivo evaluations.
AB  - Two natural Biopol polyesters, containing 8% (D400G) and 12% (D600G) of
      hydroxyvalerate component, and a synthetic polyester based on 1,4 cyclohexanediol
      [Poly(cyclohexyl-sebacate)--PCS] were studied to investigate their in vitro and
      in vivo behavior for application in musculoskeletal tissue repair. The polyesters
      were placed in direct contact with L929 fibroblasts and cell proliferation (WST
      1), cytotoxic effect (LDH), synthetic activity (total proteins) and cytokine
      production (IL-1beta, IL-6, TNFalpha) were assessed after an incubation period of
      72 hours and 7 days. Then, 12 Sprague-Dawley rats underwent dorsal subcutaneous
      implants of tested polyesters under general anesthesia. After 1 and 4 weeks from
      surgery, the animals were pharmacologically euthanized and the implants retrieved
      with surrounding tissue for histologic and histomorphometric investigations. In
      vitro results showed that D600G behaved a little worse in comparison to other
      tested polyesters in terms of cell proliferation and TNFa at 7 days. PCS
      presented the lowest total protein value at 7 days. In vivo results indicated
      that PCS implants produced a higher (p < 0.01) extent of inflammatory tissue in
      comparison to D600G at 1 week and to D400G at 4 weeks, and the lowest vascular
      densities at both experimental times. D400G seems to be the most suitable
      material for biomedical application when tested in fibroblast cultures and in the
      subcutaneous tissue of rats.

PMID- 15521221
TI  - Rheopheresis for sudden hearing loss (SHL).
AB  - Rheopheresis has met an increasing interest and application in different disease
      conditions affecting microcirculation. Its last applications are for the
      management of Macular and Cochlear disorders. The sudden hearing loss syndrome is
      a condition that affects 20 out of 100,000 persons per year, reduces the
      patient's social interaction and quality of life. It is associated with vascular
      and coagulation risk factors and it is considered as a result of local
      hypoperfusion secondary both to inflammatory and dysimmune conditions determining
      inadequate NO release and endothelial dysfunction. Rheopheresis treatment is a
      new approach which brings to satisfactory clinical results. Cascade filtration,
      heparin induced lipid precipitation and conventional plasma exchange are equally
      effective, and only 2 sessions are required for producing long lasting benefits.
      Our experience is with 60 patients, 90% of which getting from partial to complete
      recovery after treatment as measured by pure tone audiometry.

PMID- 15521222
TI  - Accidental death due to erroneous intravenous infusion of hypertonic saline
      solution for hemodialysis.
AB  - The case of a continuous hemodialysis patient who died shortly after erroneous
      infusion with undiluted hypertonic solution is reported. Autopsy showed small
      parenchymal hemorrhages in all organs. Although producers take measures to
      prevent such errors by hospital staff, further steps are suggested for types of
      dialysis requiring reinfusion of large quantities of reinfusion hemodialysis
      solution.

PMID- 15521223
TI  - Is salt restriction more important than the length of dialysis in the miracle of
      Tassin?

PMID- 15521224
TI  - Chronic skin ulcers: a regenerative simulation by topical hemotherapy.

PMID- 15521225
TI  - Effect of tubal ligation on pelvic endometriosis externa in multiparous women
      with chronic pelvic pain.
AB  - OBJECTIVE: To determine whether tubal ligation is associated with decreased
      prevalence and less severity of pelvic endometriosis in multiparous patients with
      chronic pelvic pain. MATERIAL AND METHOD: From January 1995 to April 2002, 322
      chronic pelvic pain patients underwent laparoscopy. Of these, 125 patients were
      multiparous (parity > or = 2). Their obstetric history, present contraceptive
      methods and laparoscopic findings were recorded perioperatively. The medical
      record of each patient was reviewed and analyzed. RESULTS: Among multiparous
      women with chronic pelvic pain, the prevalence of endometriosis in patients with
      and without tubal ligation was 45.1% (23 of 51 patients) and 59.5% (44 of 74
      patients), respectively. Moderate-severe endometriosis was found in 8.7% (2 of 23
      patients) and 36.4% (16 of 44 patients) among patients with and without
      sterilization. Tubal ligation was statistically significantly associated with
      severity of disease [P = 0.036, Crude OR (95% CI) = 0.17 (0.02-0.85), Adjusted OR
      (95% CI) = 0.21 (0.04-1.08)]. There was no statistically significant relationship
      between tubal ligation and prevalence of endometriosis. The small sample size of
      the study might account for this statistical result. CONCLUSION: Nearly half of
      multiparous women with chronic pelvic pain and tubal ligation had endometriosis.
      Tubal ligation was related to less severity of disease, with statistically
      significant difference.

PMID- 15521226
TI  - Positive predictive value of clinical diagnosis of endometriosis.
AB  - OBJECTIVE: To determine the positive predictive value of the combined symptoms of
      severe dysmenorrhea with the sign of tenderness and/or nodularity of the cul-de
      sac and/or uterosacral ligament(s) in diagnosing endometriosis clinically.
      MATERIAL AND METHOD: In this prospective study, 116 patients with severe
      dysmenorrhea, after excluding urinary and gastrointestinal disease, underwent
      pelvic examination by the same investigator. Women having adnexal mass on pelvic
      examination were excluded Tenderness, and also nodularity, of the cul-de-sac,
      right and left uterosacral ligament were recorded separately. The laparoscopist
      did not know the findings of the pelvic examination. The diagnosis of
      endometriosis was made visually when lesions were typical and all other lesions
      were biopsied. RESULTS: The prevalence of endometriosis was 78.4%. Tenderness,
      nodularity, tenderness and nodularity, and also tenderness or nodularity of cul
      de-sac and/or uterosacral ligament(s) were all statistically significantly
      associated with the presence of endometriosis (P = .048, .005, .004, and .004
      respectively). The positive predictive values were 85.5%, 94.0%, 94.6% and 86.7%,
      respectively. CONCLUSION: The positive predictive value of severe dysmenorrhea
      with nodularity of the cul-de-sac and/or uterosacral ligament(s) was 94.0%.

PMID- 15521227
TI  - A retrospective and comparative study between laparoscopically assisted vaginal
      hysterectomy (LAVH) and total abdominal hysterectomy (TAH).
AB  - OBJECTIVE: To compare the results of laparoscopically assisted vaginal
      hysterectomy (LAVH) and total abdominal hysterectomy (TAH). DESIGN: Retrospective
      and comparative study. SETTING: Department of Obstetrics and Gynecology, Ranong
      Hospital. SUBJECTS: 26 cases of LAVH and 63 cases of TAH who were operated on
      from February 1996 to September 2001. MATERIAL AND METHOD: Medical records of the
      patients were reviewed, by the same surgeon. The percentage and mean +/- SD data
      were analyzed a using chi-squared test and Fisher-Exact test to find the
      association. A p-value of < 0. 05 was regarded as significant. EVALUATION OF THE
      OUTCOMES: Operative time, estimated blood loss, parenteral analgesics,
      postoperative hospitalization, operative complications and operative cost.
      RESULTS: The baselines characteristics of both groups were similar The mean
      operative time for the LAVH group was 147.11 +/- 19.82 minutes, and 94.90 +/-
      7.76 minutes for the TAH group. The mean length of postoperative hospitalization
      was 3.0 +/- 0.95 days for the LAVH group versus 5.7 +/- 0.81 days in the TAH
      group. There was no significant difference in the amount of estimated blood loss
      (369.23 +/- 57.00 ml in the LAVH and 33.41 +/- 51.97 ml in the TAH, p = 0. 143).
      The LAVH group used fewer parenteral analgesics (meperidine) than the TAH group (
      64.42 +/- 17.56 mg versus 132.14 +/- 23.94 mg). The operative costs were
      11,653.85 +/- 1111.48 baht in the LAVH group and 6424.60 +/- 555.09 baht in the
      TAH group. There was one bladder injury in the LAVH group but there was no
      complication detected in the TAH group. CONCLUSION: There are some advantages as
      well as disadvantages in LAVH, compared to TAH. However, in Thailand the
      situation is not yet favorable; more learning experience is needed and more time
      to gain more confidence that LAVH is a more beneficial surgical technique.

PMID- 15521228
TI  - Reference centile chart for fetal liver length of Thai fetuses.
AB  - OBJECTIVE: To create a reference centile chart for fetal liver length of Thai
      fetuses. DESIGN: Prospective, cross-sectional study. SETTING: Division of
      Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Faculty of
      Medicine Siriraj Hospital, Mahidol University. MATERIAL AND METHOD: A total of
      752 pregnant women, who attended the antenatal clinic at Siriraj Hospital,
      Mahidol University, Bangkok, were recruited between 13-40 weeks of gestation.
      Each fetus was measured only once for the purpose of this study. Using real-time
      ultrasound with a 3.5 MHz convex transducer; the authors measured fetal liver
      length. The mean and standard deviation (SD) were estimated at each week of
      gestation using linear regression modeling. RESULTS: A total of 750 fetuses were
      measured for fetal liver length. Linear regression models were fitted to estimate
      the mean and 95% confidence interval for liver length at each gestation age. The
      centile chart of liver length was also presented CONCLUSION: A reference centile
      chart for fetal liver length of Thai fetuses has been created.

PMID- 15521229
TI  - Sexual behavior of secondary school students in Bangkok metropolis.
AB  - OBJECTIVE: To explore sexual behavior in terms of masturbation, homosexual
      contact and coitus in secondary school students in Bangkok. MATERIAL AND METHOD:
      This was a cross-sectional survey research from December, 2002 to January, 2003.
      362 students were selected by the multistages simple random sampling technique. A
      self administered questionnaire was used to collect data on baseline
      characteristics and sexual behavior of the students. RESULTS: 197 male and 165
      female students were enrolled in the present study. The mean age was 16.5 years,
      and 65.7 percent of the students were exposed to sexually explicit contents via
      the internet. 58.0 percent of the students used the internet for pornographic
      viewing. According to the sexual behavior of the students, 79.2 percent of the
      males and 9.1 percent of the females had experience in masturbation (p < 0.05).
      The male had a slightly higher in homosexual contact than the females (10.2% vs
      9.1%) but coital experience of the males was markedly significance higher than
      the females (25.4% vs 7.9%) (P < 0.05). CONCLUSION: It was concluded that sexual
      behavior in the internet era; males had more experience in all these categories
      than females. Sexual education via the internet should be improved in order to
      make adolescents understand appropriate sexual behavior and practice safer sex.

PMID- 15521230
TI  - Safety and efficacy of a simplified fixed-dose combination of stavudine,
      lamivudine and nevirapine (GPO-VIR) for the treatment of advanced HIV-infected
      patients: a 24-week study.
AB  - OBJECTIVE: To determine the efficacy and safety of the fixed-dose combination of
      stavudine (d4T), lamivudine (3TC) and nevirapine (NVP) in the treatment of
      antiretroviral naive HIV-infected Thai adults. PATIENTS AND METHOD: An open
      label, single arm trial was conducted Baseline clinical assessment and blood test
      was done on 10, antiretroviral naive HIV-infected patients, who then received a
      fixed dose combination of d4T, 3TC and NVP (GPO- VIR, Thai Government
      Pharmaceutical Organization, Bangkok, Thailand). Nevirapine was given as 200 mg
      once daily for the first 2 weeks. The patients were followed up at 2, 4, 8, 12
      and 24 weeks. A CD4 cell count and HIV-RNA assay were done at 12 and 24 weeks.
      RESULTS: One hundred and one patients were enrolled The mean baseline CD4 cell
      count and mean HIV RNA were 58.7 (57.7) cells/mm3 and 5.3 (0.5) log10, copies/mL
      respectively. At week 24th, the mean decrease in log HIV RNA was 3.6 (0.7) log10
      copies/mL [P < 0.001; 95% confidence interval (CI), 2.70-3.03]. Eighty one
      (80.2%) patients had HIV RNA < 400 copies/mL by intention-to-treat analysis (ITT)
      and 97.6% had HIV RNA < 400 copies/mL by on-treatment analysis (OT). Sixteen
      (84.2%) patients with baseline HIV RNA < or = 100,000 copies/mL and 65 (82.3%)
      patients with baseline HIV RNA > 100,000 copies/mL had viral load < 400 copies/mL
      by ITT (P = 0.842; 95% CI, -20.9%-16.2%). Sixteen (94.1%) patients with baseline
      HIV RNA < or = 100,000 copies/mL and 65 (98.5%) patients with baseline HIV RNA >
      100,000 copies/mL had viral load < 400 copies/mL by OT (P = 0.295; 95% CI, -25.5%
      3.8%). The mean CD4 cell count at week 24 was 155.1 (89.0) cells/mm3 (range 13
      402). The mean increase in CD4 cell count from baseline was 96.5 (63.5) cells/
      mm3 (P < 0.001). A total of 12% of the patients receiving d4T + 3TC + NVP
      developed skin rashes. Grade 3 or 4 hepatotoxicity was recognized in 7% of the
      patients. CONCLUSION: Fixed-dose combination of d4T + 3 TC + NVP (GPO- VIR) is
      safe, well tolerated and effective in increasing CD4 cell counts and suppression
      of HIV RNA at 24 weeks in advanced HIV-infected patients in Thailand.

PMID- 15521231
TI  - Laminectomy and postero-lateral mass plating for multilevel cervical spondylotic
      myelopathy.
AB  - There are many procedures in treating patients with multilevel cervical
      spondylotic myelopathy (CSM). Successful treatment of multilevel CSM requires
      adequate decompression and stability of the cervical spine that prevents further
      neurological deterioration. Multilevel laminectomy and instrumentation with
      lateral mass plates is associated with minimal morbidity, provides excellent
      decompression of the spinal cord, produces immediate stability of the cervical
      spine, prevents kyphotic deformity, and precludes further development of
      spondylosis at fused levels. Neurological outcome is equal or superior to
      multilevel anterior procedures because of minimal complication and prevent spinal
      deformity associated with laminoplasty or noninstrumented laminectomy. From the
      study of 7 patients with multilevel CSM who were treated with multilevel
      laminectomy and posterolateral mass plating. The neurological outcome of all 7
      patients was improved without complications after follow-up for 6 months.

PMID- 15521232
TI  - A comparison of propofol and ketamine as induction agents for cesarean section.
AB  - OBJECTIVE: To compare the neonatal and maternal effects of propofol and ketamine
      as induction agents for elective cesarean section. DESIGN: Randomized, double
      blind study. SETTING: Inpatient Obstetrics Department of Sappasitthiprasong
      Ubonratchatani Hospital, Ubonratchatani province, Thailand INTERVENTION: 2 groups
      of 50 patients each receiving either 2 mg/kg propofol or 1 mg/kg ketamine for the
      induction of anesthesia. RESULTS: The time from the induction to cord clamping (I
      C), the time from the uterine incision to cord clamping (U-C), the hemodynamic
      changes, sleep'quality, dream, recall, awareness, Postoperative nausea & vomiting
      (PONV), and Apgar scores were studied In the ketamine group Systolic Blood
      Pressure and Diastolic Blood Pressure rose about 10-25% of the baseline after the
      induction, intubation, skin incision, and cord clamping (p < 0.001) while in the
      propofol group only the Heart Rate rose (p < 0.036) after the induction, the
      intubation, the skin incision, and cord clamping. Apgar scores, the I-C time, the
      U-C time, the age, the weight and total amount of methergin and oxytocin were not
      significantly different in both groups. No incidence of awareness, nightmare and
      ketamine's phychomimetic side effects was found The incidence of unpleasant light
      sleep, dreams and PONV was low. Most patients were willing to have the same
      anesthetic technique for the next cesarean section (81.3% of the propofol group &
      86% of the ketamine group). CONCLUSION: Both propofol and ketamine can be used as
      alternative induction agents to thiopental. The addition of sevoflurane
      immediately after the induction, together with the use of midazolam and morphine
      after delivery shall prevent awareness and ketamine's phychomimetic side effects.
      However ketamine was cheaper and although Systolic Blood Pressure and Diastolic
      Blood Pressure were elevated they were within an acceptable range.

PMID- 15521233
TI  - Effect of metformin on plasma homocysteine, vitamin B12 and folic acid: a cross
      sectional study in patients with type 2 diabetes mellitus.
AB  - OBJECTIVE: To determine the effect of metformin on the levels of plasma
      homocysteine (Hcy), serum vitamin B12 and folic acid in patients with type 2
      diabetes mellitus and the relationship between cumulative metformin exposure and
      levels of plasma homocysteine (Hcy). MATERIAL AND METHOD: The cross sectional
      study was conducted to assess the effect of metformin treatment on plasma
      homocysteine (Hcy), serum vitamin B12 and folic acid in 152 type 2 diabetic out
      patients aged between 35-65 years old at the Diabetes Clinic of The Makaruk
      Hospital, Kanchanaburi, Thailand Among those, 88 and 64 patients were categorised
      to the metformin and non-metformin group according to their records of receiving
      metformin treatment for a period of a minimal 6 consecutive months before the
      study. Fasting blood was drawn from each patient and analysed for plasma
      homocysteine using the Fluorescence Polarization Immunoassay (FPIA) method (IMX
      Analyzer), and serum vitamin B12 and folic acid using the radioimmunoassay method
      RESULTS: The plasma Hcy levels showed no significant difference (p = 0.544) among
      patients in the metformin group compared with those in the non-metformin group
      (10.6+/-5.8 mol/L vs 10.4+/-4.0 mol/L). There was a significant difference (p =
      0.011) in the levels of serum vitamin B12 among patients in the metformin group
      and among those in the non-metformin group (318.0+/-192.2 pg/mL vs 434.3+/-300.7
      pg/mL). However, there was no significant difference (p = 0.090) in serum folic
      acid levels between patients in the metformin and those in the non-metformin
      group (8.8+/-5.1 ng/mL vs 7.7+/-3.8 ng/mL). The plasma Hcy levels showed a
      significant correlation with the duration of metformin treatment (p = 0.014) and
      the amount of metformin received (p = 0.015) with the Spearman correlation
      coefficient of 0.260 and 0.258 respectively. CONCLUSION: Even though the direct
      effect of metformin treatment on the plasma Hcy could not be concluded from the
      present study, it was found that there was a significant depletion of level of
      serum vitamin B12 among patients who had been on long-term metformin treatment.
      Therefore, vitamin B12 supplement is suggested for diabetic patients who are
      receiving metformin medication.

PMID- 15521234
TI  - A study of footprints in athletes and non-athletic people.
AB  - Footprint analysis is a simple, cost-effective and readily available method for
      evaluation of flat feet, to identify a person in forensic content and for shoe
      manufacturing. OBJECTIVE: To examine the footprints in athletes and non-athletes
      and to compare their foot print measurements. MATERIAL AND METHOD: Four hundred
      and ninety-two athletes and four hundred and thirty-one non-athletes were
      recruited. Their age range was eighteen to thirty five years. The athletes were
      classified by sport level : national and non-national athletes. Footprint
      devices, foot impression system, produced by Berkemann Company was used. The
      right and left foot of each subject were measured separately in a standing
      position. Descriptive Statistics, ANOVA, chi-square test and simple correlation
      were used in this study. RESULT: The length between the heel to the first toe was
      shorter than that of to the second toe in national athletes. This finding was
      opposite to the non-athletes. The metatarsal distance in national atheletes were
      significantly wider than the others. The ratio of the length of footprint and
      body height showed significant difference between athletes and non-athletes. The
      Flat Index of national athletes was longer than the others. In males, the
      percentage of the state of contacting the ground of the fifth toe was
      significantly higher among athletes than non-athletes. CONCLUSION: The footprint
      parameters were somewhat different between persons who had experience in sport
      level and general non-athletic people.

PMID- 15521235
TI  - Angiogenesis in stage IIIB squamous cell carcinoma of uterine cervix:
      reproducibility of measurement and preliminary outcome as a prognostic factor.
AB  - This study was performed to determine the reliability and replicability of IMD
      analysis using the Factor VIII immunohistochemical method. The following purpose
      was determining the relationship between IMD and clinical outcome in individual
      cervical cancer patient treated with radical radiotherapy. Twenty nine patients
      with stage IIIB cervical cancer were enrolled. Phase one was performed by using
      two pieces of tissue biopsy from different locations in the tumor from each
      patient. The IMD value was counted by the two pathologists after counterstaining
      by Factor VIII immunohistochemical method. No interobserver disagreement between
      the two pathologists was found (correlation coefficient = 0.92, 95% CI 0.82-0.96
      for the first piece of tissue and 0.85, 95% CI 0.67-0.93 for the second piece).
      There was no variability in the IMD between the 2 pieces of tissue specimens from
      different locations of the tumor Phase two followed to evaluate the relationship
      between IMD and clinical outcome in individual cervical cancer patients. Because
      of the small sample size, different patients' characteristics, different
      treatment protocol and short term follow up, there is no statistically
      significant conclusion.

PMID- 15521236
TI  - How to overcome laryngotracheal stenosis.
AB  - OBJECTIVES: To review and evaluate the outcome of the treatment of
      laryngotracheal stenosis (LTS). DESIGN: Descriptive review cases. SETTING:
      Tertiary care university hospital. PATIENTS: Series of LTS patients who were
      treated by the first author (TW) from January 2000 to January 2003. MAIN OUTCOME
      MEASURES: Leading causes of LTS, details of the lesions, therapeutic procedures,
      complications of treatment, time to and success in decannulation. RESULTS: Twenty
      one patients (9 females and 12 males), ranging in age from 1 to 32 years old were
      included in the present study. Half of the patients were under 10 years old. The
      most common site of the lesion was the subglotic lumen (14 cases), followed by
      the cervical trachea (5 cases). Patients were treated using endoscopic methods (6
      cases), laryngotracheal reconstruction (LTR) (9 cases), tracheal resection (3
      cases), and partial cricotracheal resection (3 cases). Decannulations were
      achieved in 19 patients (90.5%). Endoscopic treatment succeeded within 2-4
      procedures in properly selected cases. Despite LTR, multiple sessions of
      endoscopic laser surgery, and arytenoidectomy, decannulation was not achieved in
      two of the cases, both of whom had all-level laryngeal stenosis. Time to
      decannulation ranged from 2 to 210 days. The major causes of delayed
      decannulation were the presence of a large bare area of cartilaginous grafts and
      restenosis with granulation tissue formation CONCLUSION: Appropriate LTS
      treatment, which is based on the description of the lesion, results in a high
      decannulation rate within a proper time. Multilevel LTS, especially in the
      supraglottic and glottic area, is refractory to various treatment modalities, and
      full function of the larynx may not be restored.

PMID- 15521237
TI  - Prostatic abscesses: radiographic findings and treatment.
AB  - OBJECTIVE: To analyze the medical images and therapeutic strategies in patients
      with prostatic abscesses. METHOD: From April 1999 to August 2002, 12 patients
      with prostatic abscesses at Srinagarind Hospital, Khon Kaen, Thailand were
      reviewed The average age was 47 years (range 29 to 75). Diagnostic procedures
      included analysis of midstream urine, abscess fluid for pathogens and medical
      imaging with TRUS, CT and MRI. Therapeutic options were transrectal ultrasound
      guided drainage or conservative medical treatment. RESULTS: Almost all patients
      had predisposing diseases. All patients showed hypo-echoic masses, plus internal
      septation in 5 cases. Most lesions were located at the central gland. Their sizes
      ranged from 0.5 to 2.75 cm (average 1.51 cm) in diameter. The main pathogen was
      B. pseudomallei. On TRUS imaging, patients with melioidosis had one or more hypo
      echoic areas with internal septation, thickened wall and surrounding multiple
      small daughter abscesses. All abscesses resolved within 4 weeks, with no
      difference in the duration of treatment, despite different sizes or pathogens.
      CONCLUSIONS: Transrectal ultrasonography is useful in the diagnosis of prostatic
      abscess as well as in the guidance for aspiration and the drainage of such
      abscesses. Our data showed sonographic patterns in prostatic abscess, especially
      with melioidosis.

PMID- 15521238
TI  - No expression of human leukocyte antigen G (HLA-G) in colorectal cancer cells.
AB  - Although there is a specific antitumor immune response in the body, colorectal
      cancer cells progressively develop. This fact indicated that the cancer cells
      could have a variety of mechanisms to evade or escape the immune system. HLA-G is
      identified to inhibit the recognition of NK-cell in various kinds of cancers.
      This study investigated the expression of HLA-G in colorectal cancer. Eighty five
      specimens of colorectal cancer, carcinoma in situ and adenomatous polyp were
      examined by immunohistochemistry and RT-PCR for the detection of human leukocyte
      antigen (HLA)-G The expression of HLA-G was not found in all colorectal specimens
      (85/85) both protein level and transcription level, suggesting that the
      expression of HLA-G is not a possible immune evasion mechanism of colorectal
      cancer cell.

PMID- 15521239
TI  - Device-associated infections and patterns of antimicrobial resistance in a
      medical-surgical intensive care unit in a university hospital in Thailand.
AB  - BACKGROUND: Surveillance of nosocomial infection in the intensive care unit (ICU)
      received a high level of attention and outcome indicators are now used in
      benchmarking the quality of patient care. Since 1999 the surveillance has
      targeted three site-specific, device-associated infections, including ventilator
      associated pneumonia (VAP), central-line-related bloodstream infection (CR-BSI),
      and catheter-related urinary tract infection (CR-UTI). The authors conducted a
      two-year prospective study on the incidences of these infections acquired in an
      ICU and report herein, together with the antibiotic susceptibility patterns of
      the microorganisms isolated in an ICU. PATIENTS AND METHOD: Continuous
      prospective data collection was conducted on patients admitted to an adult
      medical-surgical ICU of a university hospital in Thailand from June 2000 to May
      2002. RESULTS: A total 1422 patients with a total of 9370 patient-days were
      enrolled in the study. The incidence of VAP, CR-BSI, and CR-UTI were 10.8/1000
      ventilator-days (95% C.I: 8.5-13.6), 2.6/1000 central-line-days (95%C.I. 1.5
      4.4), and 13.8/1000 urinary-catheter-days (95%C.I: 10.7-17.5) respectively. The
      most common causative pathogens were Escherichia coli, Acinetobacter baumannii,
      Pseudomonas aeruginosa, and Klebsiella pneumoniae. The proportion of methicillin
      resistant Staphylococcus aureus, imipenem-resistant P. aeruginosa, ceftazidime
      resistant A. baumannii, third-generation-cephalosporin-resistant K. pneumoniae,
      and quinolone-resistant E. coli were 68.8%, 30.9%, 68.5%, 44.6%, 38.3%
      respectively. CONCLUSION: The incidences of VAP and CR-BSI were comparable to the
      National Nosocomial Infection Surveillance (NNIS) report. But the incidence of CR
      UTI was over the 90th percentile. The antibiotic resistance had become a serious
      problem.

PMID- 15521241
TI  - Supratentorial lobar anaplastic ependymoma resembling cerebral metastasis: a case
      report.
AB  - A 45-year-old man presented with progressive deterioration of vision. Visual
      acuity test revealed no light perception in both eyes. The fundoscopic
      examination demonstrated pale optic discs, consistent with secondary optic
      atrophy. Preoperative neuroimaging studies revealed a well-defined contrast
      enhancing mass, 3 cm in diameter, at the left parietal region. Its radiologic
      appearances simulated those of cerebral metastases. A totally removed lesion was
      verified pathologically as an anaplastic clear cell ependymoma, which is rare in
      this location. A brief review of clinical features and neuroimaging of
      supratentorial lobar ependymoma is also included.

PMID- 15521240
TI  - Severe sand aspiration: a case report with complete recovery.
AB  - A 5-year-old boy, previously healthy, was admitted to Ratchaburi Hospital after
      being buried in a sand pile. He presented with dyspnea and tachypnea. Chest
      radiograph showed opaque particles in both main and segmental bronchi (sand
      bronchogram). The first attempt of bronchoscopy was unsatisfactory as a
      considerable amount of sand particles had migrated further into the distal
      bronchi. A second bronchoscopy was performed with 0.9% saline lavage. Most of the
      sand particles were successfully removed. Intravenous steroids and antibiotics
      were administered for treatment. The patient was discharged uneventfully by the
      end of the first week of hospitalization.

PMID- 15521242
TI  - Radiofrequency tissue volume reduction: suggested treatment for lymphatic
      malformation.
AB  - Lymphatic malformation is a benign congenital lesion but is often challenging to
      deal with. Complete excision is its treatment of choice. It has a high rate of
      recurrence, since a complete excision is difficult, and it may cause cosmetic or
      functional defect. Radiofrequency tissue volume reduction (RTVR) is used for the
      treatment of sleep-disordered breathing and other areas of surgery. A case of
      cervical lymphatic malformation reported here is effectively treated by
      radiofrequency without scar or any complication.

PMID- 15521243
TI  - Sarcoidosis presenting as papulonecrotic tuberculid-like lesions: report of a
      case.
AB  - A 50-year-old Thai woman presented with papulonecrotic tuberculid-like eruptions
      on her back and inframammary area with fever, nonproductive cough and weight
      loss. Chest radiograph showed diffuse bilateral reticulonodular opacities in both
      lungs with bilateral hilar lymph node enlargement. High resolution computed
      tomography (HRCT) of the lungs showed peribronchovascular interstitial thickening
      with multiple lymph nodes enlargement. Sputum for AFB was negative. Monotest
      (PPD) was negative. Skin biopsy revealed multiple naked granuloma compatible with
      sarcoidosis. She was treated with isoniazid, 300 mg/d, rifamipicin, 600 mg/d,
      ethambutal, 800, mg/d and pyrazinamide, 1000 mg/d for 2 months without
      improvement of skin and lung lesions. Prednisolone 45 mg/d was then administered
      adjunctive with isoniazid and rifampicin. After two weeks of treatment with
      prednisolone, the cutaneous and pulmonary lesions markedly improved Prednisolone
      was tapered in 6 months. Skin lesions, fever; dry cough disappeared and chest
      radiograph, HRCT of the chest were markedly improved.

PMID- 15521244
TI  - Cerebral venous sinus thrombosis in Behcet's disease: a case report.
AB  - Behcet's disease ( BD ) is a systemic inflammatory vascular disease with variable
      clinical manifestations and numerous clinical masquerades. The venous involvement
      may affect veins of different size with tendency for thrombosis. BD is the
      commonest cause of cerebral venous thrombosis in some Middle Eastern countries.
      However, in Thailand, this clinical entity has been rarely described as a cause
      of cerebral venous sinus thrombosis. A 38 year-old man presented with recurrent
      attacks of transient ischemic attack (TIA) for 9 months. Two months after the
      TIA, he developed right hemiparesis and persistent diffuse headache. He had a 10
      year history of recurrent oral and genital ulcers. Physical examination revealed
      bilateral uveitis, right hemiparesis, bilateral sixth cranial nerve paresis and
      bilateral papilloedema. Pathergy skin test showed positive result. Neuroimaging
      demonstrated empty delta sign on CT-scan and thrombosis of the posterior part of
      superior saggital sinus, transverse sinus, straight sinus and internal jugular
      vein on magnetic resonance venography (MRV). Cerebrospinal fluid (CSF) analysis
      revealed increased intracranial pressure and aseptic CSF profiles. Prednisolone,
      chlorambucil and anticoagulant had been prescribed. The clinical course improved
      gradually.

PMID- 15521245
TI  - Idiopathic superficial siderosis: a case report.
AB  - Superficial siderosis of the central nervous system (SSCN) is a very rare
      disorder. The clinical syndrome of SSNC consists of sensorineural hearing loss,
      cerebellar ataxia and myelopathy. The clinical syndrome together with the typical
      appearance on magnetic resonance imaging (MRI) of hyposignal intensity along the
      leptomeninges in T2 sequence permit the diagnosis of SSCN. A 58 year-old man who
      has a history of chronic progressive hearing loss and gait instability for 5
      years is presented. The neurological examination revealed bilateral sensorineural
      hearing loss, cerebellar ataxia and mild spasticity of the lower extremities. MRI
      showed classical superficial siderosis in the form of hyposignal intensity along
      the leptomeninges in T2 sequence. The prominent sites of hemosiderin deposition
      in this case were cerebellar vermis, trigeminal nerves, vestibulocochlear nerves,
      around the brain stem and spinal cord surface. Cerebrospinal fluid findings
      confirmed chronic subarachnoid hemorrhage but bleeding site could not be
      demonstrated. There is no specific treatment available for idiopathic SSCN.

PMID- 15521246
TI  - Microvascular disease and renal disease progression.

PMID- 15521247
TI  - Risk factors of morbidity in thyroid surgery: analysis of the last 5 years of
      experience in a general surgery unit.
AB  - The aim of this retrospective study is to analyze the risk factors of morbidity
      in thyroid surgery. From January 1997 to December 2001, 343 patients (69 males
      and 280 females, mean age 46.1) who underwent surgery under general anesthesia
      for thyroid disease were analyzed. In 22 (6.4%) cases the operation was a second
      thyroidectomy. The mean post-operative stay was 2 days (range: 1-7) and the mean
      follow-up was 21 months (range: 1-60 months). Statistical analysis of our data
      was performed by chi-square test and confirmed by Fisher exact test. The
      statistical analysis showed the significance of malignancy and re-surgery as risk
      factors of hypoparathyroidism and recurrent laryngeal nerve palsy. Sex, age, and
      type of operation had no influence on the medical records. The completion of
      thyroidectomy and histological malignancy increase the morbidity of thyroid
      surgery.

PMID- 15521248
TI  - Combination of video-assisted thoracoscopic surgery and hand-assisted
      laparoscopic surgery for early cancer of the thoracic esophagus.
AB  - From June 1997 to July 2002, we enrolled 10 patients with T1 esophageal squamous
      cell carcinoma according to the findings of chest computerized tomography scans
      and transesophageal ultrasound. There were nine men and one woman. The average
      age was 57.1 years (range, 43-70 years). We performed a combination of video
      assisted thoracoscopic surgery including endoscopic esophageal mobilization and
      mediastinal lymph nodes dissection for early thoracic esophageal carcinoma as
      well as hand-assisted laparoscopic gastric mobilization as an esophageal
      substitute under double-lumen intubated anesthesia. The average operative time
      was 330 minutes (range, 290-425 minutes). The average hospital stay was 11.2 days
      (range, 9-17 days). There was no surgical mortality or severe complication except
      one mild leakage of cervical esophagogastrostomy. All patients have tolerated
      solid food well and are still alive, without evidence of tumor recurrence, after
      a mean of 37.2 months of follow-up (range, 9-62 months). In conclusion, we
      suggest that a combination of video-assisted thoracoscopic esophageal
      mobilization and mediastinal lymph nodes dissection and hand-assisted
      laparoscopic mobilization of stomach via a hand-port device for esophageal
      reconstruction is a safe and feasible operation for patients with T1 thoracic
      esophageal carcinoma.

PMID- 15521249
TI  - Video-assisted thoracoscopic lobectomy for right middle lobe bronchiectasis.
AB  - The bronchiectasis process is irreversible, and only resection of the involved
      bronchiectatic segments offers the possibility of potential cure. We present our
      experience in video-assisted thoracoscopic lobectomy for localized right middle
      lobe bronchiectasis in 16 patients. From July 1994 to June 2002, we enrolled 16
      patients with right middle lobe bronchiectasis. There were nine women and seven
      men, with a mean age of 39.7 years (range, 21-67 years). The mean duration of
      symptoms such as hemoptysis and chronic purulent productive cough was 7.3 years
      (range, 2-19 years). Surgical indications included repeat pulmonary infection
      with often abundant purulent, sometimes fetid, expectoration in eight patients
      (50%), frequent massive hemoptysis in four patients (25%), and both repeat
      pulmonary infection and hemoptysis in four patients (25%). During operation, all
      patients were placed in left lateral position under double-lumen intubated
      anesthesia. Three incisions were needed. One 1-cm incision for the camera port
      was created at the seventh intercostal space along the anterior axillary line and
      the other 1- and 4-cm incisions were created at the seventh and fifth intercostal
      spaces along the midclavicular line. Right middle lobectomy could be completed by
      use of either traditional or endoscopic instruments. The mean total operative
      time was 87 minutes (range, 60-110 minutes). The mean hospital stay was 6 days
      (range, 4-11 days). One patient suffered from a mild hemothorax complication that
      needed 10 days of pleural drainage. There was no surgical mortality in this
      study. The mean follow-up period was 45 months (range, 10-94 months). Overall, 14
      (87.5%) patients were asymptomatic, and the other 2 (12.5%) obtained apparent
      symptomatic improvement after operation. Video-assisted thoracoscopic lobectomy
      for right middle lobe bronchiectasis is technically feasible using our approach
      and is potential safe in treating patients with localized right middle lobe
      bronchiectasis.

PMID- 15521250
TI  - Salivary gland tumors: a 10-year retrospective study of survival in relation to
      size, histopathological examination of the tumor, and nodal status.
AB  - Salivary gland neoplasms represent the most complex and diverse group of tumors
      encountered by the head and neck oncologist. Their diagnosis and management is
      complicated by their relative infrequency. The significance of the study was to
      analyze the different types of salivary gland tumors, the modalities of treatment
      given, and their varied outcomes in relation with morbidity, prognosis, and
      survival rate. A total of 436 patients were treated for salivary gland neoplasm
      at Madras Medical College and Research Institute between 1991 and 2001, and the
      results were analyzed retrospectively. The patients were between 11 and 72 years
      of age (mean, 41.5 years), and 334 were male and 102 were female. They were from
      different socioeconomic groups. Fine-needle aspiration cytology was done for all
      patients that presented with salivary gland swelling. Univariate analysis was
      done, the confidence interval and odds ratio were calculated, and the
      significance was noted. Kaplan-Meier survival analysis was estimated, and the
      results were analyzed. Pleomorphic adenoma was the most common benign tumor
      affecting the salivary glands. In our series, 155 patients had malignant parotid
      gland neoplasms, and 20 patients had cervical lymph node metastasis at the time
      of presentation. Facial nerve paralysis was noted in 21 cases. The recurrence
      after total parotidectomy for malignant salivary gland tumors was effectively
      managed with external beam irradiation in 19 patients. The survival, prognosis,
      and the mortality rate of the malignant parotid neoplasms and their relation to
      the sex of the patient, histopathological type of tumor, nodal status, and size
      of the tumor were analyzed.

PMID- 15521251
TI  - Axillary gland involvement in breast carcinomas is not always metastatic: a case
      report.
AB  - We describe an unusual case of coexistence of carcinoma in the breast and an
      ipsilateral enlargement of axillary lymph nodes caused by tuberculosis. Accurate
      diagnosis has helped us in down staging the carcinoma in the breast and also
      identifying curable disease.

PMID- 15521252
TI  - Evolution of staples and clips for vascular anastomoses.
AB  - Because of the development of less invasive surgical techniques, there is an
      increasing demand for vascular anastomosing techniques that require less exposure
      of the operating field. This paper reviews the most important representatives of
      staples, clips, and other mechanical devices for vascular anastomosing described
      over the last five decades. This report is organized in three parts: (1) the
      history of clipping and stapling devices, (2) development of the Vessel Closure
      System (VCS) clips, and (3) current and potential status of mechanical vascular
      anastomotic devices. A Medline literature search was conducted and publications
      on the use of staples and/or clips for the creation of vascular anastomoses
      identified with extensive cross-referencing. The first literature description of
      a mechanical vascular stapling device was by Gudov in 1950. This and other
      reports from the Soviet Union stimulated brisk, competitive development of
      vascular anastomotic devices in Europe, North America, and Japan. Fasteners
      included staples, penetrating pin-rings, or toothed stainless steel clips, none
      of which gained acceptance because of their complexity and inability to
      facilitate end-to-side anastomoses. A more convenient and less traumatic
      anastomotic system (VCS Clip applier system) was introduced into clinical
      practice in 1995. This system differs from staples in that it is non-penetrating.
      A wide variety of reports have described the advantages, both technical and
      biological, that clips provide over conventional needle-and-suture, particularly
      for the construction of vascular access for hemodialysis. A steady evolution of
      mechanical vascular anastomotic devices has sought to eliminate the technical and
      biological disadvantages of conventional suturing. Although the conventional hand
      sewn, overcast non-absorbable suture remains the "gold" standard, newer
      techniques such as the non-penetrating arcuate-legged VCS clips are gaining
      acceptance as a useful addition to the vascular surgeons' armamentarium.

PMID- 15521254
TI  - Aden kidney transplantation.
AB  - During the first Yemeni Congress of Uro-Nephrology in Aden, an international team
      performed the first kidney tranplantations in the region. We report the
      difficulties encountered and discuss the pros and cons for transplantations in
      developing countries.

PMID- 15521253
TI  - An unusual case of ectopic or "parasitic" leiomyoma excised by laparoscopic
      surgery.
AB  - A 47-year-old woman underwent a laparoscopic resection of a large ectopic or
      "parasitic" fibroid filling the pelvis and placed within the rectosigmoid
      mesentery. The tumor was excised completely without a need for hysterectomy.
      Immunohistochemical and ultrastructural studies confirmed a "parasitic"
      leiomyoma, excluding sarcoma or a gastrointestinal stromal tumor. Because of its
      bizarre location in relation to the large bowel, a combined general surgical and
      gynecological approach was used successfully. The pathology of this rare tumor is
      reviewed.

PMID- 15521255
TI  - Management of bilateral breast carcinoma: long-term results.
AB  - The aim of this study was to document the clinical features and long-term
      outcomes in 43 cases of bilateral breast carcinoma. All the women were diagnosed
      by a single surgeon who had evaluated 13,443 patients with breast-related
      complaints over a 40-year period. At the initial cancer diagnosis, 28 patients
      (65%) were of premenopausal age (< or = 46 years; group 1) and 15 (35%) were
      postmenopausal (> 46 years; group 2). The median interval between initial and
      subsequent cancer was 24 months (range, 12-288 months) in group 1 and 20 months
      (range, 14-252 months) in group 2 (P > 0.05). The distribution of initial cancer
      types based on pathological examination was ductal adenocarcinoma in 28 (65%)
      cases; lobular carcinoma in 5 (12%) cases; comedocarcinoma in 5 (12%) cases;
      papillary carcinoma in 2 (4.5%) cases; papillary combined with squamous cell
      carcinoma in 1 (2%) case; and lobular combined with medullary carcinoma in 2
      (4.5%) cases. There were no significant differences between the groups with
      respect to the distribution of types of surgery used for the initial and
      subsequent carcinomas. Tumor locations were symmetrical in 26 (60%) patients. The
      mean palpable mass sizes for the initial and subsequent tumors in group 1 were 3
      +/- 1.4 (range, 1-8 cm) and 1.3 +/- 0.5 cm (range, 1-2 cm), respectively. The
      corresponding means for group 2 were 2.3 +/- 1.8 (range, 0.9-7 cm) and 1.3 +/-
      0.5 cm (range, 1-2 cm). The 10- and 20-year disease-free survival rates for group
      1 versus group 2 were 32% versus 27% and 10% versus 8%, respectively. The rates
      of axillary lymph node metastasis from the primary cancer in groups 1 and 2 were
      statistically similar; however, the rate of axillary lymph node metastasis from
      subsequent cancer in group 1 was significantly higher than that in group 2 (P =
      0.02). The lactation period (after each child born) in group 1 was significantly
      longer than that in group 2 (P = 0.04). Group 1 had a higher rate of distant
      metastasis at 20 years (P = 0.03), but the groups' local recurrence rates at this
      stage were similar. Log-rank analysis revealed no significant differences between
      the groups' 10- and 20-year patient survival rates. Subsequent breast cancer was
      not detected on mammography in 4 (9%) of the 43 patients. In these cases, the
      tumors were diagnosed by ultrasonography after physical examination revealed
      suspicious findings at symmetrical locations. The findings suggest that women who
      are diagnosed with primary cancer before menopause are at greater risk for
      distant metastasis than postmenopausal women, when subsequent cancer is detected
      in the contralateral breast. Herein, the risk for metastasis is only assessed
      after cancer is detected in the other breast. The premenopausal women had a
      significantly longer mean lactation period. Extended lactation may be a risk
      factor for breast cancer development in this age group, but this needs further
      investigation.

PMID- 15521256
TI  - Massive lower gastrointestinal bleeding in typhoid fever.
AB  - Typhoid fever is an infectious disease that is usually treated medically and
      rarely needs surgical intervention. In this paper, we report three cases of
      severe colonic involvement in salmonella infection in patients traveling in or
      coming from endemic areas, resulting in ulceration and massive anorectal
      bleeding.

PMID- 15521257
TI  - Gunshot wound of the heart with embolism to the right axillary artery.
AB  - The rarity of bullet emboli leads to frequent delays in diagnosis and inadequate
      early management. A case report of a bullet entering the right ventricle and
      embolization to the right axillary artery is presented. Our recent experience
      with this entity is described, and 160 cases reported in the English literature
      are reviewed and summarized.

PMID- 15521258
TI  - Milestones in medical imaging.

PMID- 15521259
TI  - The future of refractive surgery: confluence of techniques and staged delivery.

PMID- 15521260
TI  - Alignment in customized laser in situ keratomileusis.
AB  - PURPOSE: To identify fundamentals of beam alignment in customized laser in situ
      keratomileusis (LASIK) with a special focus on the Nidek NAVEX system. METHODS:
      Analysis of Nidek specifications and recommendations for beam alignment with
      regard to a critical case example are presented. The potential impact of
      misalignment (tilt and defocus) is calculated. Cyclotorsional error evaluation in
      a normal LASIK population was performed by video image comparison. Potential
      problems of infrared-based eyetracking systems are discussed. RESULTS: The laser
      beam should be aligned with reference to the line of sight (LOS) when customized
      segmental laser ablation is applied. Only in cases with significant offset
      between the LOS and the visual axis it is recommended not to use segmental
      ablation and to manually align the beam toward the visual axis. Eye drift (tilt)
      as well as defocus should be avoided since undercorrection and irregular
      astigmatism can result. Almost 30% of eyes in a normal LASIK population showed a
      torsional error of 5 degrees to 10 degrees (9% more than 10 degrees) on video
      based image comparison. Eye-trackers not only are defined by take-up speed and
      latency, but also by their sensibility (picking the real center of the pupil) and
      robustness (keeping it tracked during surgery). Errors due to parallax and reflex
      effects can systematically influence the performance of an eyetracker.
      CONCLUSION: Correct alignment is difficult to achieve but is of fundamental
      importance in customized LASIK. Strict standardization and further improvement in
      the alignment strategy is necessary to achieve more consistent results in
      customized LASIK.

PMID- 15521261
TI  - Higher order aberrations with aspheric ablations using the Nidek EC-5000 CX II
      laser.
AB  - PURPOSE: To analyze the change in higher order aberrations in myopic and myopic
      astigmatic eyes following an aspheric ablation profile for laser in situ
      keratomileusis (LASIK) using a Nidek EC-5000 CX II excimer laser system. METHODS:
      We performed a retrospective audit of 38 eyes (19 patients) with myopia and
      myopic astigmatism. A customized aspheric transition zone profile (CATz) was used
      in all eyes (profile 4) with an ablation zone of 5 mm and a transition zone of 9
      mm using FinalFit software and a Nidek EC-5000 CX II excimer laser system.
      RESULTS: Mean higher order aberrations (RMS) increased from 0.42 microm at
      baseline to 0.57 microm at 6-month follow-up. Mean spherical aberrations (Z12)
      increased from 0.02 microm at baseline to 0.33 microm after LASIK. Mean spherical
      aberration defocus equivalent (DEQ) increased from 0.56 microm at baseline to
      1.54 at 6 months after surgery. Mean trefoil (Z6) was -0.11 microm at baseline
      and -0.14 microm at the 3-month examination. Mean coma (Z7) was -0.09 microm at
      baseline and -0.10 microm after surgery. Mean coma (Z8) was -0.03 at baseline and
      0 at the 3-month examination. Mean trefoil (Z9) was -0.03 at baseline and -0.12
      at the 3-month examination. CONCLUSION: The amount of postoperative higher order
      aberrations in these myopic eyes was acceptable. However, the clinical
      significance of these numerical changes in aberrations is not known.

PMID- 15521262
TI  - Comparison of cross cylinder ablation using the optimized ablation transition
      zone and the torsion error detector for correction of astigmatism.
AB  - PURPOSE: To compare the safety and efficacy of laser in situ keratomileusis
      (LASIK) in correcting high myopic astigmatism using two different ablation
      profiles using the Nidek EC-5000 CX II laser). METHODS: Fifteen patients (25
      eyes) had LASIK for compound myopic astigmatism, using the Optimized Ablation
      Transition Zone (OATz) ablation profile and activated torsion error detection
      (TED). Results were compared with those obtained with a cross cylinder ablation
      profile for myopic astigmatism. RESULTS: For eyes treated with TED, on
      postoperative day 7, 76% had visual acuity equal to or better than baseline best
      spectacle-corrected visual acuity (BSCVA) and 56% of eyes had overcorrected
      astigmatism. On postoperative day 20, none of the eyes had residual astigmatism
      more than 1.00 D and 72% eyes were within +/-0.50 D cylinder; 92% of eyes had
      residual astigmatism within 30 degrees of the preoperative axis and 12% remained
      astigmatically overcorrected at 20 days. Eighty-eight percent of eyes were either
      fully corrected or had mild myopic astigmatism. Comparison of results with cross
      cylinder ablation showed that 24% had overcorrection and 60% of patients with
      high astigmatism were overcorrected up to 1.75 D and developed hyperopic
      astigmatism in the opposite axis. Results with the cross cylinder ablation
      profile were good up to 2.00 D of myopic astigmatism. CONCLUSIONS: Correction of
      astigmatism using the OATz profile and TED with the Nidek EC-5000 CX II laser
      produced good results in high as well as pure astigmatism treatments, compared to
      the cross cylinder ablation profile. Ablation depth was greater in OATz with TED
      based corrections. Overcorrections were less with OATz with TED, and residual
      astigmatism was at the same baseline axis, thereby increasing patient
      satisfaction.

PMID- 15521263
TI  - Aspheric ablation with the Nidek EC-5000 CX II with OPD-Scan objective analysis.
AB  - PURPOSE: To analyze the efficacy, predictability, stability, and safety of laser
      in situ keratomileusis (LASIK) to correct myopia and myopic astigmatism using the
      Nidek EC-5000 CX II laser and the Customized Aspheric Transition Zone (CATz)
      profile. METHODS: We conducted a retrospective analysis of 100 eyes (50 patients)
      with myopic astigmatism. A CATz profile was used in all eyes (profile 4) with an
      ablation zone of 5 mm and a transition zone of 9 mm, using Nidek FinalFit
      software. RESULTS: Average patient age was 39 years (range 21 to 69 yr).
      Preoperative mean spherical equivalent refraction was -4.70 +/- 2.53 D (range 
      11.88 to -0.50 D), mean preoperative sphere was -4.31 +/- 2.53 D (range -11.25 to
      -0.25 D), and mean preoperative cylinder was -0.78 +/- 0.69 D (range -3.25 to 0).
      Postoperative mean spherical equivalent refraction at 6 months was 0.12 +/- 0.53
      D (range -1.63 to +0.88 D), mean postoperative sphere was 0.02 +/- 0.56 D (range 
      1.50 to +2.00 D), and mean postoperative cylinder was -0.29 +/- 0.50 D (range 0
      to -1.75 D). Uncorrected visual acuity was 6/6 or better in 58% (58 eyes) and
      better than 6/12 in 93% (93 eyes). CONCLUSION: LASIK with the Nidek EC-5000 CX II
      laser and the CATz profile was effective, reasonably predictable, stable, and
      safe for correction of myopic astigmatism with a spherical component between 
      0.25 and -11.25 D, and a cylindrical component up to 3.25 D, using the techniques
      in this study. Astigmatism was undercorrected with the current algorithm.

PMID- 15521264
TI  - Laser in situ keratomileusis for high myopia using a small ablation zone and
      large aspheric transition zone.
AB  - PURPOSE: To evaluate the efficacy and predictability of laser in situ
      keratomileusis (LASIK) using the Nidek NAVEX system with a small ablation
      (optical, OZ) zone and a large aspheric transition zone (OATz). METHODS: We
      report a prospective nonrandomized study of LASIK for high myopia using a small
      ablation in 23 eyes of 18 patients. The optical zone was between 3 and 3.8 mm and
      transition zone (TZ) was between 7 and 7.8 mm. Preoperative examination included
      best-spectacle corrected visual acuity (BSCVA), refraction, and corneal
      topography. All eyes were measured by the Nidek OPD-Scan and data were imported
      to FinalFit software. Aspheric profile (OATz) numbers 5 to 7 were used. BSCVA,
      uncorrected spectacle visual acuity (UCVA), refraction, and subjective evaluation
      of glare and night vision by questionnaire were recorded after surgery. RESULTS:
      At baseline, mean spherical equivalent refraction was -7.03 +/- 2.39 D (range 
      5.50 to -15.50 D). Postoperative UCVA was better than 20/25 in 95.65% of eyes 3
      months after LASIK. Postoperative refraction was within +/- 0.50 D of emmetropia
      in 91.3% of eyes and within +/- 1.00 D in all eyes. No eye lost lines of BSCVA;
      52.17% of eyes gained 1 line and 13.04% of eyes gained 2 lines. No patient
      reported significant glare or night vision problems on subjective questionnaire.
      CONCLUSION: LASIK with a small ablation (optical) zone and high aspheric
      transition zone using the Nidek NAVEX system was effective, predictable, and
      relatively safe for correction of high myopia.

PMID- 15521265
TI  - Comparison of conventional and OATz ablation profiles for laser in situ
      keratomileusis to correct myopia up to -10.00 diopters.
AB  - PURPOSE: To compare results of laser in situ keratomileusis (LASIK) using two
      different ablation profiles for correction of myopia between -0.50 and -10.00 D
      with the Nidek NAVEX system. METHODS: In a prospective nonrandomized study, 249
      myopic eyes (151 patients) had LASIK for correction of myopia. The Nidek MK-2000
      micro-keratome and the Nidek NAVEX excimer laser system were used in all eyes.
      Conventional LASIK was performed in 112 eyes of 64 patients with a 6.0-mm
      ablation zone and 7.5-mm transition zone (conventional group). LASIK with the
      Nidek OATz ablation profile was performed in 137 eyes of 87 patients, with
      variable ablation and transition zones (OATz group). Mean baseline manifest
      refraction was -4.11 +/- 1.83 D in the conventional group and -5.45 +/- 2.27 D in
      the OATz group. Baseline best spectacle- corrected visual acuity was 20/20 or
      better in 83.9% of eyes in the conventional group and 81.0% of eyes in the OATz
      group. RESULTS: Mean follow-up was 3.6 months (range 3 to 8 mo). At last follow
      up, manifest refraction was within +/-0.50 D of emmetropia in 86% of eyes (within
      +/-1.00 D in 99.1%) in the conventional group and 94.2% of eyes (within +/-1.00 D
      in 100%) in the OATz group. Uncorrected visual acuity was 20/40 or better in all
      eyes. No eyes in either group lost 2 or more lines of BSCVA. CONCLUSIONS: The
      Nidek NAVEX system was safe and predictable in correcting myopia up to -10.00 D
      with the OATz ablation profile. OATz LASIK was similar to conventional LASIK in
      both refractive and visual outcomes.

PMID- 15521266
TI  - Correction of myopia and myopic astigmatism with customized ablation using the
      Nidek NAVEX system.

PMID- 15521267
TI  - Correlation of wavefront data and corneal asphericity with contrast sensitivity
      after laser in situ keratomileusis for myopia.
AB  - PURPOSE: To investigate the relationship between contrast sensitivity (CS),
      Zernike wavefront aberrations (WFA), and asphericity after laser in situ
      keratomileusis (LASIK) for myopia. METHODS: LASIK was performed using the Nidek
      EC-5000 excimer laser with custom aspheric transition zone (CATz) ablations.
      Total and high order (HO) WFA of 71 eyes (37 patients) undergoing LASIK in March
      2003 were measured before and at 1 month postoperatively with the Nidek OPD-Scan
      aberrometer at a 4-mm pupil entrance; asphericity was measured at 6 mm (Q index).
      Preoperative and 1 to 3-month postoperative contrast sensitivity were evaluated
      with the Vector Vision CSV-1000 at 3, 6, 12, and 18 CPD; the Area Under the Log
      Contrast Sensitivity Function (AULCSF) was calculated. Uncorrected-visual acuity
      (UCVA) was evaluated. RESULTS: One month after LASIK, CS decreased significantly
      at 6 CPD and above (P<.05), then returned to normal at 3 months (P=.33).
      Postoperative AULCSF correlated with patient age (P=.04) but not with total WFA
      (P=.13), HO WFA (P=.50), or asphericity (P=.22). Postoperative Logmar UCVA
      correlated with postoperative total and HO WFA (P<.05). Postoperative total WFA
      correlated with spherical equivalent refraction (P<.0001); HO WFA correlated with
      Strehl ratio (P=.004) and asphericity (P=.03). The HO WFA increase was 0.065
      microm (P<.05) and did not correlate with preoperative refraction (P=.40).
      Increase in asphericity correlated with corneal refractive change and was
      predicted by the parabolic Munnerlyn equation (P<.0001). CONCLUSIONS: After
      LASIK, AULCSF was not dependent on WFA, but mainly on patient age. WFA results
      correlated well with postoperative spherical equivalent refraction, asphericity,
      and Strehl ratio. These conclusions support a published hypothesis that
      postoperative low amount of WFA does not completely fit contrast sensitivity
      measurements.

PMID- 15521268
TI  - Whole eye wavefront aberrations in Mexican male subjects.
AB  - PURPOSE: To analyze the characteristics, incidence, and appearance of wavefront
      aberrations in undilated, normal, unoperated eyes. METHODS: Eighty-eight eyes of
      44 healthy male Mexican subjects (mean age 25.32 years, range 18 to 36 yr) were
      divided into three groups based on uncorrected visual acuity of greater than or
      equal to 20/20, 20/30, or 20/40. UCVA measurements were obtained using an Acuity
      Max computer screen chart. Wavefront aberrations were measured with the Nidek OPD
      Scan ARK 10000, Ver. 1.11b. All measurements were carried out at the same center
      by the same technician during a single session, following manufacturer
      instructions. Background illumination was 3 Lux. RESULTS: Wavefront aberration
      measurements for each group were statistically analyzed using StatView; an
      average eye was characterized and the resulting aberrations were simulated using
      MATLAB. We obtained wavefront aberration maps for the 20/20 undilated normal
      unoperated eyes for total, low, and high order aberration coefficients. Wavefront
      maps for right eyes were practically the same as those for left eyes. Higher
      aberrations did not contribute substantially to total wavefront analysis.
      CONCLUSIONS: Average aberrations of this "normal eye" will be used as criteria to
      decide the necessity of wavefront-guided ablation in our facilities. We will
      focus on the nearly zero average of high order aberrations in this normal whole
      eye as a reference to be matched.

PMID- 15521269
TI  - The effect of laser in situ keratomileusis on low contrast vision.
AB  - PURPOSE: To determine the effects of laser in situ keratomileusis (LASIK) on low
      contrast visual acuity. METHODS: Thirty eyes of 15 LASIK patients with myopia and
      astigmatism were evaluated preoperatively, and 1 and 3 months postoperatively.
      High contrast visual acuity (HCVA), low contrast visual acuity (LCVA), and
      contrast threshold were determined. RESULTS: Mean spherical correction (SE) was 
      3.24 +/- 1.90 D; 16 eyes had a mean SE between -1.00 and -3.00 D, and 14 eyes
      were between -3.25 and -6.50 D. There was no significant change in HCVA observed
      at 1 and 3 months in any eye. There was a decrease in LCVA in eyes with a
      correction >3 D SE at 1 month (P=.04), which returned to normal at 3 months
      (P=.13). There was an increase in the contrast threshold at 1 month (P=.016).
      When eyes were divided into groups, those with >3D SE correction had an increase
      in contrast threshold at 1 month (P=.002); no change was seen in eyes with <3D SE
      correction (P=.15). At 3 months, contrast threshold was similar to baseline
      values in all eyes (P=.226). CONCLUSION: LASIK transiently decreased low contrast
      visual function in patients with greater than 3.00 D of myopic correction.

PMID- 15521270
TI  - Laser epithelial keratomileusis with mitomycin C: indications and limits.
AB  - PURPOSE: To assess the advantages and safety of using mitomycin C (MMC) with
      laser epithelial keratomileusis (LASEK) by measuring high order aberrations of
      the cornea. METHODS: We analyzed the results of 86 eyes that had LASEK plus a
      brushstroke of MMC 0.01%. Another group of 100 eyes had LASEK only (control
      group). Mean follow-up was 312 days for the MMC group and 774 days for the
      control group. A Nidek EC-5000 laser was used in all eyes. We measured mean
      refractive error, best spectacle-corrected visual acuity (BSCVA), haze, and high
      order aberrations before and at 1 month and nearly 1 year after LASEK. RESULTS:
      Mean baseline spherical equivalent refraction was -6.80 +/- 3.00 D for the MMC
      group and -6.00 +/- 3.10 D for the control group (P=.34). In eyes with low myopia
      (-1.20 to -10.80 D), a single ablation zone of 6 mm with a transition zone of 8
      mm was used, and in the higher myopia group (-5.60 to -15.50 D), smoothing and a
      cross sphere procedure (+0.75 D) were used. Mean spherical equivalent refraction
      after LASEK for low myopia in the MMC group at last examination (mean follow-up
      312 days) was +0.50 +/- 0.93, and 0 +/- 0.34 D for the control group. Mean
      spherical equivalent refraction after LASEK for high myopia in the MMC group at
      last examination (mean follow-up 312 days) was +0.50 +/- 1.03 D, and +0.40 +/-
      0.78 D for the control group. Mean haze in the low myopia MMC group was 0.06 and
      in the control group, 0.11; in the high myopia MMC group it was 0.1, and in the
      control group, 0.27 (all differences P<.05). No differences between baseline and
      postoperative BSCVA were noted. Early and late overcorrection were noted in the
      MMC group. Increased high order aberrations were evident at 1 month and 1 year in
      the MMC groups. CONCLUSIONS: The use of mitomycin C 0.01% with LASEK
      significantly decreased subepithelial haze. However, refractive outcome was less
      predictable. High order aberrations increased after LASEK with MMC. Additional
      studies with longer follow-up are necessary to evaluate long-term effects, and
      ideal MMC concentration and exposure time.

PMID- 15521271
TI  - One-year results of custom laser epithelial keratomileusis with the Nidek system.
AB  - PURPOSE: To evaluate long-term results of custom laser epithelial keratomileusis
      (LASEK) for correction of myopia and hyperopia using the Custom Ablation
      Transition Zone (CATz) software and hyaluronic acid masking fluid (Laservis) for
      final corneal smoothing. METHODS: We conducted a prospective study of 297 eyes of
      167 patients. All eyes had LASEK for correction of myopia or hyperopia. The Nidek
      EC-5000 excimer laser, FinalFit software, and CATz ablation profile was used in
      all eyes. Laservis was used as masking fluid to remove corneal micro
      irregularities during the final phase of the treatment. RESULTS: Mean
      preoperative spherical equivalent refraction was -5.46 +/- 2.57 D (range -14.13
      to +3.50 D). At 1 year after LASEK, mean spherical equivalent refraction was 
      0.15 +/- 0.50 D (range -4.00 D to +1.00 D). CONCLUSIONS: LASEK with the Nidek EC
      5000 excimer laser, FinalFit and Custom Ablation Transition Zone (CATz) software,
      with corneal smoothing, was safe and effective at 1 year after surgery.

PMID- 15521272
TI  - One-year follow-up of custom phototherapeutic keratectomy.
AB  - PURPOSE: Phototherapeutic keratectomy is a safe and effective treatment for many
      superficial diseases of the cornea. We applied intraoperative, epithelium-free,
      topography-based corneal aberrometry as a basis for custom phototherapeutic
      keratectomy (CPK) in highly aberrated eyes with opacities or irregularities
      consequent to previous refractive treatment, ulcers, keratitis, trauma or corneal
      dystrophies. METHODS: We evaluated eyes undergoing CPK for corneal opacities and
      or irregularities due to previous refractive treatment, keratitis, trauma, or
      corneal dystrophies, and treated 52 eyes of 50 patients. Customization was based
      on corneal topography-based aberrometry, performed intraoperatively after removal
      of corneal epithelium. Results were evaluated immediately and subsequent cycles
      of CPK were applied when necessary. Eyes were followed for 1 year. RESULTS: For
      the 52 eyes of 50 patients, mean preoperative haze was of 1.7 +/- 1.47 in eyes
      with previous refractive surgery. Mean preoperative corneal thickness
      (pachymetry) was 399.5 +/- 127.1 microm. Mean preoperative spherical equivalent
      refraction was -1.13 +/- 3.33 D (range -9.38 to +10.00 D). No eye reached 20/15
      BSCVA, and only 59% could see 20/30 BSCVA. At the final, 12-month examination,
      mean spherical equivalent refraction was -0.38 +/- 4.11 D (range -10.88 to +6.00
      D). Eighty-eight percent of eyes reached 20/30 or better BSCVA, and 25% had 20/15
      or better BSCVA. No eye developed corneal ectasia. CONCLUSIONS: At 1 year after
      surgery, custom phototherapeutic keratectomy (CPK) provided a reliable tool for
      treatment of highly aberrated eyes, and provided a surgical alternative to
      penetrating keratoplasty.

PMID- 15521273
TI  - Advanced surface ablation for presbyopia using the Nidek EC-5000 laser.
AB  - PURPOSE: To present 1 to 6-month follow-up results of laser in situ
      keratomileusis (LASIK) using multizone presbyopic advanced surface ablation
      (PASA) with a peripheral near zone. METHODS: LASIK was performed on 28 eyes of 17
      patients (10 men and 7 women; mean age 49.8 years with a range of 37 to 62
      years). Eyes had primary or enhancement treatments with the Nidek EC-5000 excimer
      laser. Three techniques were used: 1) total transepithelial ablation, 2) surface
      ablation for far vision ametropia correction, and 3) concentric peripheral near
      zone presbyopia correction (technique developed by Dr. A. Telandro with a
      modified nomogram by Dr. R. Cantu for surface ablation). One surgeon (RC)
      performed all surgery. RESULTS: We present the preoperative and postoperative
      measurements for far and near uncorrected visual acuity, total high order
      aberrations, spherical aberration (Z-12), asphericity Q index, eccentricity
      corneal shape factor, and total coma and trefoil aberrations. Increases occurred
      in negative spherical aberration, negative asphericity index, and positive
      eccentricity corneal shape factor. CONCLUSIONS: Advanced surface ablation for
      presbyopia with a concentric peripheral near zone is a promising approach for
      surgical correction of presbyopia and potentially could be used with any advanced
      surface ablation procedure. Increases in negative spherical aberration and
      asphericity/ eccentricity indices seemed to increase the depth of focus of the
      eye, improving the near vision.

PMID- 15521274
TI  - Pseudo-accommodative cornea: a new concept for correction of presbyopia.
AB  - PURPOSE: Efficacy, predictability, stability, and safety of multifocal ablation
      with a peripheral near zone for correction of myopia, hyperopia, and presbyopia
      was assessed. METHODS: We performed a retrospective study of 83 hyperopic eyes
      and 77 myopic eyes. Baseline mean spherical equivalent refraction in the
      hyperopia group was +1.54 +/- 0.90 D (range 0 to +4.00 D) and in the myopia
      group, -4.31 +/- 2.62 D (range -12.00 to -0.25 D). Mean near addition was 2.40 D
      in the hyperopia group and 1.75 D in the myopia group. All eyes had multifocal
      laser in situ keratomileusis (LASIK) with a peripheral near zone, using a Nidek
      EC-5000 excimer laser. Pseudoaccommodative cornea (PAC) software version 6T was
      used to calculate the multistep ablation profile. RESULTS: Three months after
      surgery, 80 eyes (96.4%) of the hyperopia group and 75 eyes (97.4%) of the myopia
      group were examined. Postoperative mean spherical equivalent refraction was -0.19
      +/- 0.58 D (range -1.75 to +1.00 D) in the hyperopia group and -0.50 +/- 0.75 D
      (range -2.50 to -0.75 D) in the myopia group. Fifty-eight eyes (72.5%) of the
      hyperopia group and 50 eyes (66.7%) of the myopia group were within +/-0.50 D of
      emmetropia. One percent of eyes in the hyperopia group and no eyes in the myopia
      group lost 2 or more lines of BSCVA; 5% of eyes in the hyperopia group and 12%
      eyes in the myopia group gained 2 or more lines of BSCVA. Mean near addition was
      0.11 D in the hyperopia group and 0.07 in the myopia group. Binocular unaided
      near visual acuity was J3 or better in all eyes of both groups and J1 or better
      in 35% eyes in the hyperopia group and 41% of eyes in the myopia group.
      CONCLUSION: Multistep multifocal ablation with a peripheral near zone using the
      Nidek EC-5000 excimer laser and PAC software version 6T was effective,
      predictable, stable, and relatively safe over a period of 3 months.

PMID- 15521275
TI  - Progressive keratectasia after laser in situ keratomileusis.
AB  - PURPOSE: We describe ten patients who developed progressive keratectasia
      following laser in situ keratomileusis (LASIK) and identify possible factors that
      may lead to ectasia. METHODS: In this retrospective study, we reviewed the files
      of 3,634 patients (6941 eyes) who had LASIK between March 2000 and April 2003.
      Ten patients (14 eyes, 0.2%) developed progressive keratectasia. We also
      evaluated consequent therapeutic measures and final visual status of these
      patients. RESULTS: Patients were examined at a mean 24.9 +/- 8.1 months after
      LASIK. Ectasia developed within a mean 14 +/- 0.3 months after surgery. At
      baseline, mean keratometric power was 44.7 +/- 2.30 D, mean corneal thickness was
      516 +/- 18.9 microm, and mean attempted correction was -10.85 +/- 3.20 D. We
      found a statistically significant correlation between residual stromal thickness,
      attempted correction, and occurrence of progressive keratectasia. We also found
      that preexisting abnormal corneal topography was a risk factor for progressive
      keratectasia. Ultimately, most patients had reasonable visual acuity after
      penetrating keratoplasty. CONCLUSION: Progressive keratectasia is a vision
      threatening complication of LASIK that may occur in previously healthy or
      diseased eyes. The most important risk factors are residual stromal thickness and
      preexisting abnormal corneal topography. Penetrating keratoplasty may be a
      reasonable therapeutic measure for severe cases of progressive keratectasia.

PMID- 15521276
TI  - Intraoperative microkeratome complications in 47,094 laser in situ keratomileusis
      surgeries.
AB  - PURPOSE: We evaluated the incidence and intraoperative microkeratome-related
      complications in laser in situ keratomileusis (LASIK). METHODS: We present non
      randomized, retrospective, comparative, interventional case series. We reviewed
      the records of patients who underwent LASIK from August 2000 to March 2004 at
      Excimer Laser Santa Cruz, Sao Paulo, Brazil (47,094 eyes). We identified 369 eyes
      (0.0078%) with an intraoperative complication. Data were collected regarding
      microkeratome, average keratometric power, and type of complication. RESULTS: The
      Hansatome microkeratome was the most common microkeratome used (34,182 eyes;
      73%), followed by the Automated Corneal Shaper-ACS (11,164 eyes, 24%) and the
      Nidek MK-2000 (1748 eyes, 3.7%). Intraoperative complications were more common
      with the ACS (1.26%) than with the Hansatome (0.63%) and MK-2000 (0.63%) (P<.001;
      P=.03; respectively). Complications included incomplete flaps (0.23%),
      buttonholes (0.13%), thin flaps (0.08%), and free flaps (0.08%). Buttonholes were
      more frequent with the ACS (0.34%) than with the Hansatome (0.06%) (P<.001) and
      free flaps were more common with the ACS (0.20%) and MK-2000 (0.29%) than with
      the Hansatome (0.04%) (P<.001). Keratometric power of eyes with intraoperative
      complications was significantly higher in the ACS group compared to the Hansatome
      group. CONCLUSIONS: Intraoperative complications were more common with the ACS
      than with the Hansatome or MK-2000. Buttonholes were most frequent with the ACS,
      and the Hansatome had the lowest incidence of free flaps.

PMID- 15521277
TI  - Patient motivation for laser in situ keratomileusis in the State of Bihar.
AB  - PURPOSE: To evaluate the main reasons for seeking laser in situ keratomileusis
      (LASIK) and patient satisfaction after surgery in the socioeconomically
      underdeveloped eastern state of Bihar, India. METHODS: This retrospective study
      evaluated results of the first 100 consecutive patients (169 eyes) who had LASIK
      at our center from July 2002 to September 2003. RESULTS: Of the 100 patients, 65%
      were male and 35% were female. Ninety percent of male patients were between 18
      and 24 years old; they sought LASIK to achieve an uncorrected visual acuity of
      6/6 to 6/9-the basic qualifying criterion for jobs in the railway and defense
      services. Eighty-six percent of female patients were of marrying age. At 1 month
      after LASIK, 93% of patients achieved an UCVA of 6/6, 4% had UCVA between 6/9 to
      6/12, and only 1% had <6/60. CONCLUSION: In the socioeconomically poor state of
      Bihar, the main reason for males in our study to seek LASIK was to enhance their
      job prospects. In females, the main reason was to improve facial appearance in
      order to enhance marriage prospects.

PMID- 15521278
TI  - Smoothness of ablation on polymethylmethacrylate plates with four scanning
      excimer lasers.
AB  - PURPOSE: To perform a quantitative evaluation of smoothness of ablation on
      polymethylmethacrylate (PMMA) using four scanning excimer lasers available
      commercially for photorefractive surgery. METHODS: Ablations were done on PMMA
      plates with dimensions 100 x 50 x 1 mm. Four scanning excimer lasers were used,
      two with flying spot technology (Zeiss-Meditec MEL-70, and a Russian-made unit,
      Microscan) and two Nidek models with scanning slit delivery systems and an
      expanding iris diaphragm (EC-5000 and EC-5000 CX). Forty PMMA plates were ablated
      with standard -3.00-D settings using an ablation zone of 6 mm; each laser ablated
      10 plates. Measurements were made in the center of each plate with the Zygo
      microscope, based on the principle of white light interferometry. Smoothness of
      ablation was characterized by three surface parameters (RMS, Ra, PV). RMS was
      considered the most significant parameter. RESULTS: The smoothest surface was
      obtained in samples produced by Zeiss-Meditec MEL-70 unit (RMS=112 +/- 23 nm),
      followed by the Nidek EC-5000 CX (RMS=153 +/- 12 nm), and the Microscan (RMS=181
      +/- 11 nm). The smoothness of ablation produced by the Nidek EC-5000 unit
      (RMS=329 +/- 39 nm) was significantly less than the other three lasers (P<.01).
      CONCLUSIONS: Scanning excimer lasers based on flying spot technology--Zeiss
      Meditec MEL-70 and Microscan, as well as the Nidek EC-5000 CX with FlexScan-
      created smoother ablations on PMMA plates compared to the older Nidek EC-5000
      unit.

PMID- 15521279
TI  - Correlation of Nidek OPD-Scan objective refraction with subjective refraction.
AB  - PURPOSE: The aim of this study was to quantify how closely the Nidek OPD-Scan
      objective refraction correlated with subjective refraction. METHODS: A
      retrospective audit of the preoperative refraction of 80 myopic and myopic
      astigmatic eyes before laser in situ keratomileusis (LASIK) or laser
      supepithelial keratomileusis (LASEK) was performed. Objective refraction in the 5
      mm zone was performed using a Nidek OPD-Scan. Subjective refraction was performed
      by a senior optometrist. Statistical analysis of sphere, cylinder, and spherical
      equivalent refraction measurements was then performed. RESULTS: Spherical
      measurements correlated well with a linear regression equation, with a
      correlation coefficient of 0.97. Cylinder measurements correlated less well, with
      a correlation coefficient of 0.85. Spherical equivalent refraction measurements
      correlated well, with a correlation coefficient of 0.97. Analyzing the numerical
      difference between each objective refraction and its corresponding subjective
      refraction, the majority of values were only 0.50 D apart for sphere, cylinder,
      and spherical equivalent refraction. CONCLUSION: There was good correlation
      between objective OPD-Scan and subjective refraction, especially for sphere and
      spherical equivalent refraction measurements, with regression gradients and
      correlation coefficients close to 1.

PMID- 15521280
TI  - Confocal microscopy in early diagnosis of Acanthamoeba keratitis.
AB  - PURPOSE: This study correlated confocal microscopic images obtained using the
      Nidek ConfoScan 2.0 System in corneas with clinical suspicion of Acanthamoeba
      keratitis, with diagnosis confirmed by either cytological and/or histological
      analysis. METHODS: Fifteen eyes of 14 patients with a clinical diagnosis of
      Acanthamoeba keratitis underwent confocal microscopy evaluation. RESULTS: Fifteen
      eyes of 14 patients (one bilateral case) showed Acanthamoeba keratitis
      alterations that ranged from massive infestation to cicatricial opacity in the
      stroma. Ten patients (71%) were females. Mean age was 26 years (range 19 to 37
      yr). All patients were contact lens wearers. CONCLUSION: Confocal microscopy was
      a useful, noninvasive technique in the diagnosis and treatment of Acanthamoeba
      keratitis, especially in those cases in which corneal scraping, cytological
      analysis, and culture are negative. It also eliminated the necessity of tissue
      biopsy, considered an invasive procedure.

PMID- 15521281
TI  - Pearls, tips, and tricks for use of the Nidek OPD-Scan and FinalFit software.
AB  - Nidek's FinalFit/NAVEX is likely the most comprehensive customized ablation
      platform currently available. This software/laser platform offers a full range of
      customized ablation treatments from aspheric ablation, topography-based, and
      (entire eye) aberrometry-based custom ablation. With the plethora of options
      available, a surgeon can treat a full spectrum of cases, ranging from primary
      eyes to highly aberrated eyes and those requiring retreatments due to previous
      refractive surgery. As with any new indication or surgical technique, a learning
      curve is involved and one should proceed step-by-step and carefully monitor
      his/her initial results.

PMID- 15521282
TI  - Nidek corneal navigator software for topographic analysis of corneal states.

PMID- 15521283
TI  - Managed care's effect on minority physicians and their patients.
AB  - Using data from a cross-sectional mail survey that ultimately included 1,215
      physicians, the termination and denial rates of minority physicians' managed care
      contracts across all specialties were compared with nonminority physicians. The
      study measured termination and denial rates using several variables, including
      physicians who were denied managed care contracts more than three times in the
      previous two years. The authors found that 4.4% of the Hispanic physicians,
      compared with 3.3% of the Caucasian physicians, 6.4% of the African-American
      physicians, and 5.8% of the Asian physicians, were denied managed care contracts
      more than three times during this period. The authors also found patient
      characteristics of those physicians with the highest rates of contract denials
      and terminations in the state of Maryland, and concluded differences were
      observed in the selection of physicians by MCOs, even after considering market
      competition.

PMID- 15521284
TI  - High-quality or unknown-quality health care?

PMID- 15521285
TI  - Identification of medication-adherence barriers and strategies to increase
      adherence in recipients of renal transplants.
AB  - One hundred randomly selected renal transplant centers (RTCs) were surveyed
      concerning barriers to medication adherence by recipents of renal transplants
      (RTRs). Responders were asked to list factors that they believe decrease RTRs'
      medication adherence. Survey responses were used to develop another survey, which
      was mailed to a different set of 100 RTCs. Barriers identified included issues
      concerning the particular medication prescribed, patient knowledge and
      comprehension concerning how to take the medication, patients' desire or
      motivation to take the medication, patient-health care professional relationship,
      and the ability of the caregiver to deliver optimum care. Barriers that received
      at least a 75% agreement were given to a multidisciplinary focus group, who
      developed strategies to circumvent the barriers. Strategies addressing barriers
      are discussed.

PMID- 15521286
TI  - Cost effectiveness of bortezomib in the treatment of advanced multiple myeloma.
AB  - This study evaluated the cost effectiveness of bortezomib in relapsed, refractory
      myeloma, relative to best supportive care (BSC) and thalidomide. Data were
      derived from the phase 2 pivotal study of bortezomib, a Delphi panel of six
      myeloma thought leaders, and published literature. Objective assumptions
      regarding treatment choices and consequences (response and complications), and
      actual cost data were used. Bortezomib was found to be cost effective relative to
      BSC and thalidomide. Sensitivity analyses demonstrated the robustness of the
      results. These data suggest that bortezomib provides a cost-effective treatment
      option and the best value (in terms of cost/life-yr gained) among the currently
      available therapeutic options for relapsed, refractory myeloma.

PMID- 15521287
TI  - Managed care foundations champion health system change.

PMID- 15521288
TI  - What's in an acronym?

PMID- 15521289
TI  - Therapist and/or medication manager?

PMID- 15521290
TI  - What the law allows.

PMID- 15521291
TI  - What is our vision?

PMID- 15521292
TI  - ANCC certification for PMH APRNs.

PMID- 15521293
TI  - End-of-life care: a challenge to psychiatric nurses.

PMID- 15521294
TI  - Nursing care at the end of life.

PMID- 15521295
TI  - The tidal model: developing a person-centered approach to psychiatric and mental
      health nursing.
AB  - TOPIC: Overview of the theoretical and practical basis of a new model of
      psychiatric and mental health nursing practice. PURPOSE: To illustrate the
      history of the development of the model and some of the processes that aim to re
      empower the patient and develop genuinely collaborative approaches to care.
      SOURCES: Literature review, author's research, and related clinical experience.
      CONCLUSIONS: The Tidal Model provides a practice framework for the exploration of
      the patient's need for nursing and the provision of individually tailored care.

PMID- 15521296
TI  - Nature vs. nurture: two brothers with schizophrenia.
AB  - TOPIC: The nature vs. nurture argument as it pertains to two brothers. PURPOSE:
      To explore the synergistic effects of heritability and environment in the cases
      of two brothers with schizophrenia. SOURCES: Review of the literature and the
      authors' clinical experience. CONCLUSIONS: The nature vs. nurture dichotomy may
      not be as relevant as looking at the interaction between these two forces.

PMID- 15521297
TI  - Working with adult homicide survivors, part I: impact and sequelae of murder.
AB  - TOPIC: The impact and sequelae of murder on surviving family and significant
      others. PURPOSE: To describe the aftermath of murder: losses, reactions,
      secondary victimization of surviving family members, contextual issues that may
      affect the grieving process, and psychological impact. SOURCES: Review of the
      literature and the author's own clinical work. CONCLUSIONS: Loss of a loved one
      through sudden violence often results in concomitant factors that may compromise
      the ability of homicide survivors to deal with the trauma, process the loss, and
      proceed through the tasks of grieving. Further, these factors may put family
      members at risk for development of posttraumatic stress disorder and complicated
      mourning.

PMID- 15521298
TI  - Meditation and psychotherapy: an effective combination.

PMID- 15521299
TI  - Intervention or interaction?

PMID- 15521300
TI  - A more civil union.

PMID- 15521301
TI  - Teaching healthy anger management.
AB  - TOPIC: Teaching anger management in the community. PURPOSE: To describe anger
      management and offer guidelines for assessing potential participants and teaching
      healthy behaviors. SOURCES: Drawing from the literature, more than 10 years of
      quantitative and qualitative studies by our research team, and 5 years of
      experience in conducting anger management groups, the author presents basic
      principles of teaching anger management. A model is described for a 4-week group
      for women. CONCLUSIONS: Anger management has wide applicability to a variety of
      constituencies for both primary and secondary prevention. Advanced practice
      psychiatric nurses are well-qualified to provide this psychoeducational
      intervention.

PMID- 15521302
TI  - Male survivors' perspectives of incest/sexual abuse.
AB  - PURPOSE: To show how understanding the aftereffects of incest and other forms of
      sexual abuse from male survivors' perspectives may help clinicians identify males
      with a possible history of sexual abuse. METHODS: Audiotaped interviews with 25
      male survivors described the aftereffects in eight life areas. Data were analyzed
      by the double-coding qualitative method. FINDINGS: Themes identified included
      isolation, anger, depression/suicidal feelings, addictions, or low sense of self,
      and distant relationships with men and women. CONCLUSIONS: Clinicians need to
      explore the possibility of a history of sexual abuse with males who seek
      treatment for addictions, suicidal ideation, depression, and chronic low self
      esteem.

PMID- 15521303
TI  - The real and the researchable: a brief review of the contribution of John Bowlby
      (1907-1990).
AB  - TOPIC: John Bowlby. PURPOSE: To provide a broad overview of Bowlby's life and
      contribution to psychoanalytic theory and to examine his departure from the
      British school of object relations. SOURCES: Literature review and author's
      interpretation of material. CONCLUSIONS: Bowlby's ideas remain relevant although
      controversial and merit continued study.

PMID- 15521304
TI  - Dopaminergic and serotonergic receptor function in the CNS.

PMID- 15521305
TI  - Setting fees: the conscious and unconscious meanings of money.

PMID- 15521306
TI  - The nursing shortage: what you can do.

PMID- 15521307
TI  - Making the most of the latest in healthcare tools.

PMID- 15521308
TI  - Matters of the heart.

PMID- 15521309
TI  - More or less psychotherapy education?

PMID- 15521310
TI  - The aftermath of violence.

PMID- 15521311
TI  - Working with adult homicide survivors, part II: helping family members cope with
      murder.
AB  - TOPIC: The process of coping with the murder of a loved one and ways in which
      therapists may assist homicide survivors in the aftermath. PURPOSES: To identify
      coping strategies used by homicide survivors, describe variables that may affect
      the grieving process, discuss treatment strategies related to posttraumatic
      stress and complicated mourning within the framework of outcome-oriented nursing
      process, and explore the concept of posttraumatic growth. SOURCES: Review of the
      literature and the author's own clinical work. CONCLUSIONS: Coping with the
      aftermath of murder is a difficult and long-lasting process. While no one method
      or strategy for assisting homicide survivors works for everyone, a combination of
      therapeutic approaches-including crisis intervention, individual, family, and
      group therapy, peer support groups, pharmacological-that may assist the survivor
      in working through the trauma and grief of such a violent loss.

PMID- 15521312
TI  - Critical incident stress debriefing: a health promotion model for workplace
      violence.
AB  - PURPOSE: To view the global impact of violence as a critical incident. DATA
      SOURCES: Published literature, author's experience. CONCLUSIONS: Psychiatric
      nurses can use the critical incident stress debriefing protocol to minimize
      adverse outcomes after a traumatic event. Workplace violence threatens the safety
      and well-being of nurses. Psychiatric nurses are more likely to encounter
      workplace violence than nurses in other settings and must prepare themselves
      using proactive health-promoting activities, for example the critical incident
      stress debriefing (CISD) model. This health-promotion model provides immediate
      emotional support and education about normal stress reactions, and may reduce the
      risk of chronic and disabling emotional and physical consequences.

PMID- 15521313
TI  - Care after chaos: use of critical incident stress debriefing after traumatic
      workplace events.
AB  - CISD is a specific model of group debriefing, which can be used to accelerate
      recovery from traumatic work-place events. The impact of critical incidents may
      be debilitating-from recurrent intrusive images, persistent fear, displaced
      anger, guilt, and isolation. CISD can accomplish psychological closure,
      prevention, and mitigation of traumatic stress, and promote return to normalcy,
      benefiting the individual, organization, and the community at large. The field of
      critical incident stress management is open to advanced practice nurses who seek
      to apply their crisis-intervention expertise within a nontraditional role and
      workplace setting. With specialized training, the advanced practice nurse may
      pursue a career as a crisis-response provider, working independently or with an
      established CISM team. Practice requirements include CISM certification, along
      with the acquisition of a referral source. The prevention and mitigation of
      traumatic stress can yield a rewarding career in CISM.

PMID- 15521314
TI  - The view from the edge of the cauldron.

PMID- 15521315
TI  - Adrenergic, cholinergic, GABAergic, and glutaminergic receptor function in the
      CNS.

PMID- 15521316
TI  - Concentrations of a Koi herpesvirus (KHV) in tissues of experimentally infected
      Cyprinus carpio koi as assessed by real-time TaqMan PCR.
AB  - The Koi herpesvirus (KHV) is a herpes-like virus now recognized as a worldwide
      cause of mortality among populations of koi Cyprinus carpio koi and common carp
      Cyprinus carpio carpio. Temperature is a key factor influencing virus replication
      both in cell culture and in the tissues of experimentally infected fish. Genomic
      DNA sequences were used to optimize a rapid real-time TaqMan PCR assay to detect
      and quantify KHV DNA as found in the tissues of virus-exposed fish. The assay
      allowed analytical enumeration of target KHV genome copies ranging from 10(1) to
      10(7) molecules as present in infected cell lines or fish tissues. The new assay
      was specific for KHV and did not detect DNA from 3 related herpes-like viruses
      found in fish, the Cyprinid herpesvirus 1 (CyHV-1), Cyprinid herpesvirus 2 (CyHV
      2), Ictalurid herpesvirus 1 (IcHV-1) or the KF-1 cell line used for virus growth.
      Concentrations of KHV DNA were evaluated in 7 different tissues of replicate
      groups of virus-exposed koi held at water temperatures of 13, 18, 23 and 28
      degrees C. Viral DNA was detected among virus-exposed koi at all 4 water
      temperatures but mortality was only observed among fish at 18, 23, and 28 degrees
      C. Time and temperature and the interactions between them affected concentrations
      of viral DNA detected in tissues of koi exposed to KHV. Although there were no
      recognized patterns to viral DNA concentrations as found in different tissues
      over time, KHV genome copies for all tissues increased with time post virus
      exposure and with water temperature. The remarkably rapid and systemic spread of
      the virus was demonstrated by the presence of viral DNA in multiple tissues 1 d
      post virus exposure. The greatest DNA concentrations found were in the gill,
      kidney and spleen, with virus genome equivalents consistently from 10(8) to 10(9)
      per 10(6) host cells. High levels of KHV DNA were also found in the mucus, liver,
      gut, and brain. Koi surviving infection at 62 to 64 d post virus exposure
      contained lower KHV genome copies (up to 1.99 x 10(2) per 10(6) host cells) as
      present in gill, kidney or brain tissues.

PMID- 15521317
TI  - Epizootic cutaneous papillomatosis, cortisol and male ornamentation during and
      after breeding in the roach Rutilus rutilus.
AB  - The prevalence of epidermal papillomatosis in roach is known to peak during the
      spawning period and to be higher in males than in females. The high occurrence of
      papillomatosis in polluted waters suggests that stress may contribute to the
      outbreak of the disease. However, little is known about breeding-induced stress
      in fish and its relationship with diseases. In this study, plasma cortisol
      concentration, hematocrit and the relative size of the spleen were determined in
      healthy and diseased male and female roach Rutilus rutilus during and shortly
      after spawning in a wild population. In addition, the sexual ornamentation
      (breeding tubercles on the lateral sides and on the frontal) of male roach during
      spawning was examined. Plasma cortisol concentration was higher during than after
      the spawning period, and higher in males than in females during spawning,
      indicating a spawning-induced stress and higher spawning stress among males.
      There was no correlation between cortisol concentration and the intensity of
      papillomatosis (number of scales under papilloma tumors) among the diseased fish.
      However, the significant interaction sex x disease status revealed by ANCOVA
      suggested that diseased males could be more prone to increased cortisol levels
      than diseased females or healthy males. Hematocrit values (ratio of the volume of
      red blood cells to total volume of blood) but not condition factor were lowered
      in papilloma-diseased fish after spawning. The relative size of the spleen was
      greater in males than in females. The number of frontal breeding tubercles
      correlated negatively with the intensity of papillomatosis. Experimental studies
      are needed to investigate the association of papillomatosis with stress and
      cortisol.

PMID- 15521318
TI  - Efficacy of emamectin benzoate in the control of Argulus coregoni (Crustacea:
      Branchiura) on rainbow trout Oncorhynchus mykiss.
AB  - Efficacy of in-feed treatment with emamectin benzoate (Slice) for the control of
      ectoparasitic Argulus coregoni on rainbow trout Oncorhynchus mykiss was tested
      under laboratory and field conditions. In both experiments fish were fed with
      fish feed to deliver a therapeutic dose of 0 (control) or 50 microg emamectin
      benzoate kg(-1) d(-1) (treatment) for a period of 7 d. After 3 d of challenge
      with A. coregoni in the laboratory, the infestation level in treated fish was
      lower than that observed in the controls (p < 0.001). Efficacy of 100% against
      newly hatched A. coregoni metanauplii and adults and 80% against juveniles was
      observed. In the field, trial medication was undertaken at 2 sections on a flow
      through canal with 1 wk between treatments. Mean infestations of 100 to 200 A.
      coregoni per fish with 100% prevalence was recorded prior to medication.
      Following the treatment, the mean infestation of A. coregoni on fish declined to
      31 lice per fish at Section A and 2.5 lice per fish at Section B. Then, after 28
      d of treatment, the number of lice per fish was < 1 at Section A; in contrast the
      mean number of A. coregoni per fish at the control section was > 20. The
      prevalence of A. coregoni remained < 50% over a period of 72 d of treatment, but
      started to increase again thereafter. This suggests that emamectin benzoate
      concentration in fish remained at a level high enough to kill A. coregoni over a
      period of 9 wk. Emamectin benzoate was very effective in the control of A.
      coregoni infesting trout.

PMID- 15521320
TI  - Pathological changes in African hyperoliid frogs due to a myxosporidian infection
      with a new species of Hoferellus (Myxozoa).
AB  - A proliferous, polycystic and sometimes fatal kidney disease due to an infection
      with myxosporidia is reported in 24 of 28 hyperoliid frogs (Afrixalus dorsalis,
      Hyperolius concolor, Hyperolius sp.) from Nigeria, Ghana and Tanzania. In line
      with pathological changes in fish, the disease is described as 'frog kidney
      enlargement disease' (FKED). Myxosporidian plasmodia, different developmental
      stages and spores occurred in the kidney, ureter, and urinary bladder and in the
      intestine of the frogs. The parasite belongs to the genus Hoferellus and is
      presented as a new species: H. anurae n. sp. Spores are similar in size and
      structure to other Hoferellus species in fish but differ by the presence of a
      more prominent suture line and shorter caudal appendages. This is the first
      report on a Hoferellus species in amphibians as well as the first report of the
      genus Hoferellus in African vertebrates.

PMID- 15521319
TI  - Real-time quantitative polymerase chain reaction (QPCR) to identify Myxobolus
      cerebralis in rainbow trout Oncorhynchus mykiss.
AB  - This study describes the development of a TaqMan real-time quantitative
      polymerase chain reaction (QPCR) technique using the heat-shock protein 70 (Hsp
      70) and 18S ribosomal DNA (18S rDNA) sequences to identify Myxobolus cerebralis
      and attempt to quantify infection severity within rainbow trout fry Oncorhynchus
      mykiss. Rainbow trout for this study were exposed to M. cerebralis under natural
      river conditions and examined for infection by histology, polymerase chain
      reaction (PCR) and QPCR analysis at 900 Celsius temperature units (CTUs)
      following exposure. Detection sensitivity by QPCR was shown to be equal to
      traditional PCR but greater than histopathology. Primer/probe combinations
      developed for this study were capable of specifically detecting M. cerebralis DNA
      in infected fish tissue and single triactinomyxon (TAM) spores with a sensitivity
      of 12.5 and 6.3 pg microl(-1) of DNA for the Hsp 70 and 18S rDNA sequences,
      respectively. A strong relationship between QPCR and infection severity was found
      for the Hsp 70 probe when parasite copy number and histology scores of 0-4 were
      compared (R2 = 0.96, p = 0.003). However, a reduction in copy number was observed
      at higher histology scores for the 18S probe (scores of 4 and 5) and the Hsp 70
      probe (score of 5). The results of this study demonstrate that QPCR analysis is
      an effective tool for detecting M. cerebralis in fish tissue and may provide a
      relative indication of infection severity.

PMID- 15521321
TI  - Physiology and lipid metabolism of Littorina saxatilis infected with trematodes.
AB  - Physiological and biochemical alterations in Littorina saxatilis infected with
      larval trematodes were investigated and compared with the metabolism of non
      parasitized snails. Oxygen consumption rates of infected snails differed from
      those of non-infected controls in medium sized individuals (30 to 130 mg) but not
      in very large infected individuals (> 200 mg). Small snails (0.5 to 8.5 mg) were
      seldom infected by parasites, and this size-class consisted only of non-infected
      specimens. The specific oxygen consumption rate of infected snails was not
      dependent on their mass and remained constant over the size ranges investigated.
      Alterations in the snail metabolism appeared to be connected to injuries to
      digestive gland tissues caused by the parasites. The glycogen concentration and
      fatty acids of neutral lipids and phospholipids in the digestive gland were
      determined. Infected snails differed from uninfected snails in the complete
      absence of glycogen in digestive gland and had proportionally higher quantities
      of eicosenoic (20:1) acid in the total phospholipids. It remains unclear whether
      infection by trematodes activates enzymes in the snail's digestive gland to
      synthesize eicosenoic (20:1) acid, or whether the sporocysts themselves possess
      these enzymes. The role of phospholipid fatty acids in the regulation and
      maintenance of the parasite's metabolism is briefly considered. Biochemical
      alterations observed in the fatty acid composition may have an adaptive
      significance, by helping to stabilize the host-parasite system.

PMID- 15521322
TI  - Development of monoclonal antibodies for detection of necrotizing
      hepatopancreatitis in penaeid shrimp.
AB  - Monoclonal antibodies (MAbs) were produced against necrotizing hepatopancreatitis
      bacteria (NHP-B) of penaeid shrimp. The MAbs tested in dot-immunoblot (D-IB)
      assays were capable of detecting the NHP-B in hepatopancreas samples collected
      from moribund juvenile Litopenaeus vannamei during an experimentally induced NHP
      B infection. The MAbs were also screened by immunohistochemistry (IHC) using case
      submissions that were determined to be infected not only by histology, but also
      polymerase chain reaction (PCR) and in situ hybridization (ISH) assays using
      specific digoxigenin (DIG)-labeled probes on histological sections prepared from
      naturally infected shrimp. Two of the MAbs were chosen for development of
      detection methods for NHP. The MAbs were tested using IHC methods on Davidson's
      alcohol-formalin-acetic acid (AFA) fixed tissue sections and identified NHP-B
      infected cells and tissues in a pattern similar to that seen with DIG-labeled NHP
      specific gene probes. None of the MAbs reacted with tissue from specific pathogen
      free (SPF) shrimp or with shrimp tissues infected with a rickettsia-like
      bacteria, Vibrio sp., Campylobacter sp., and Spiroplasma sp. The MAbs were found
      to be negative against these other organisms, demonstrating that they are species
      specific and useful for rapid diagnostic detection of NHP-B.

PMID- 15521323
TI  - Establishment of a continuous embryonic cell line from Japanese flounder
      Paralichthys olivaceus for virus isolation.
AB  - A continuous cell line, the flounder embryonic cell line (FEC), was established
      from gastrula-stage embryos of a marine cultured fish, the Japanese flounder
      Paralichthys olivaceus and cultured for more than 200 d with more than 60
      passages. FEC cells were cultured in Dulbecco's Modified Eagle's Medium (DMEM)
      supplemented with antibiotics, fetal bovine serum (FBS), sea perch serum (SPS),
      and basic fibroblast growth factor (bFGF). The cells were small and round, and
      grew actively and stably in culture. The effect of temperature, FBS concentration
      and bFGF on FEC cell growth was examined. Cells grew well between 24 and 30
      degrees C, but had a reduced growth rate below 18 degrees C. The growth rate of
      FEC cells in medium containing 15% FBS was higher than that in medium containing
      7.5% FBS. Addition of bFGF to the medium also significantly increased the growth
      rate. Chromosome analysis revealed that FEC cells have a normal diploid karyotype
      with 2n = 48. High survival rate was obtained after cryopreservation of cell
      cultures. The susceptibility of the cell line to piscine viruses was examined.
      Two viruses tested were shown to induce CPE (cytopathic effect) on FEC cells. FEC
      cell culture infected with fish iridovirus was further elucidated by electron
      microscopy. Many virus particles were found in the cytoplasm of the virus
      infected FEC cells. These results indicated that the FEC cell line could be
      potentially used to isolate and study fish viruses.

PMID- 15521324
TI  - Important disease conditions of newly cultured species in intensive freshwater
      farms in Greece: first incidence of nodavirus infection in Acipenser sp.
AB  - We describe here the main pathological conditions of freshwater fish recently
      introduced for intensive rearing (open ponds and recirculating freshwater
      systems) in Greece. Sturgeon were susceptible to skeletal abnormalities of the
      spine (scoliosis and lordosis) of unknown aetiology. Horizontal transmission of
      nodavirus from infected sea bass to sturgeon was detected for the first time.
      This caused serious pathology and clinical signs, such as lethargy and imbalance,
      leading to secondary infections with Aeromonas hydrophila and Trichodina sp. and
      chronic, but steady, mortality. Sea bass were very susceptible to nodavirus
      infection, monogenean infections and gas bubble disease. Mullet reared under
      recirculated and open-flow conditions were very sensitive to Chilodonella sp.
      infection, whereas catfish were susceptible to infection with Ichthyophthirius
      sp. leading to secondary infections with A. hydrophila, Saprolegnia sp. and
      Myxobacteria spp. Tilapia were very susceptible to gas bubble disease and A.
      hydrophila. This bacterium was associated with management manipulations for all
      species and fully responsive to corrective hygiene methods.

PMID- 15521325
TI  - Safety and protective effect of a disinfectant (STEL water) for white spot
      syndrome viral infection in shrimp.
AB  - The efficacy of STEL water for protection against white spot syndrome virus
      (WSSV) infection was evaluated using shrimp. The LC50 of residual chlorine (Cl-)
      in STEL water for brood-stock and 2-mo-old shrimp were 2.3 and 3.2 ppm,
      respectively. All 2-month-old shrimp raised in seawater containing more than 40
      microl 2l(-1) of a WSSV-infected tissue homogenate died within 3 d post-exposure
      (dpe). Thus, a 10-fold dose of 400 microl 2 l(-1) was used in the disinfection
      tests. Low concentrations of STEL water effectively prevented mortality of shrimp
      at this challenge dose. All 2-month-old shrimp exposed to seawater with 400
      microl of viral homogenate disinfected with STEL water at Cl- concentrations over
      0.125 ppm for 1 and 10 min, lived until 5 dpe. With 5-mo-old shrimp, all positive
      control shrimps died within 3 dpe, whereas most shrimp reared in seawater
      disinfected with STEL water for 1 h before addition of homogenate lived until 5
      dpe. Results suggested that continuous disinfection of seawater with STEL water
      may be effective for preventing WSSV infection in shrimp.

PMID- 15521326
TI  - Formulation development and human in vitro-in vivo correlation for a novel,
      monolithic controlled-release matrix system of high load and highly water-soluble
      drug niacin.
AB  - Novel, controlled-release formulations for high drug load, highly water soluble
      compound niacin based on polyethylene oxide (PEO) and hydroxypropylmethyl
      cellulose (HPMC) matrices were developed and investigated. The effect of sodium
      bicarbonate as a modulator of swelling, erosion, and drug release and its impact
      on changes in the kinetics of axial swelling and gel strength were evaluated by
      textural analysis during dissolution study. The drug release rate from PEO-based
      matrices was faster and correlated with lower gel strength, greater water uptake,
      and greater matrix erosion. Slower release rate and greater release duration
      correlated significantly with greater matrix swelling with negligible matrix
      erosion for the HPMC-based matrix system. Inclusion of sodium bicarbonate in the
      polymeric matrix salted out the macromolecules and increased gel strength and gel
      viscosity, especially in the vicinity of the swelling fronts. An in vivo study in
      human subjects after administration of the formulations and a commercial product
      exhibited similar plasma concentrations. For the formulation of interest, the
      mean drug fraction absorbed by the body was calculated by the Wagner-Nelson
      technique, and a level A "in vitro-in vivo correlation" was observed between the
      percent released in vitro and percent absorbed in vivo. The developed
      formulations appear to be robust and easy to manufacture with maximum flexibility
      with respect to drug dose, polymeric carriers, duration, and kinetics of drug
      release.

PMID- 15521327
TI  - Determination of amorphous content of lactose samples by solution calorimetry.
AB  - Earlies studies suggest that solution calorimetry can be used to determine the
      extent of amorphous content of drug and excipient, when the solubility and
      dissolution rate of the compound in the chosen solvent are reasonably high. In
      the present study, the use of solution calorimetry for assessment of amorphous
      content of a sample that is not completely dissolved in a solvent was evaluated.
      Physical mixtures of lactose and spray-dried lactose samples were analysed. The
      amorphous content of the physical mixtures and the spray-dried samples varied
      from 0% to 100% determined by isothermal microcalorimetry. The enthalpy of
      solution (delta(sol)H) was determined in water. The lactose samples were
      dissolved quickly in water. In addition, the enthalpy accompanied with an
      addition of a lactose sample in an over saturated aqueous solution (delta(sat)H)
      (prepared from the corresponding lactose sample) was determined. The lactose
      sample did not completely dissolve in the over saturated aqueous solution. An
      excellent correlation was observed between delta(sol)H and the amorphous content
      of the samples. Interestingly, there was a linear correlation also between
      delta(sat)H and the amorphous content of the samples. Further, a linear
      relationship was observed between the delta(sat)H and the delta(sol)H of the
      samples. Therefore, solution calorimetry may represent a rapid and simple method
      for determining the amorphous content also in samples that are not completely
      dissolved in the solvent.

PMID- 15521328
TI  - Study of in-vitro release characteristics of carbamazepine extended release
      semisolid matrix filled capsules based on Gelucires.
AB  - Various extended release carbamazepine (CBZ) formulations have been developed
      previously, in order to reduce the frequency of dosing in chronic therapy and to
      decrease the variability in drug plasma concentration. In the present study, the
      suitability of different grades of Gelucires (G, glyceride based excipients) to
      formulate CBZ extended release capsules by the application of semisolid matrix
      (SSM) filling capsule technology was investigated. The possible modification of
      CBZ release kinetics by using Gelucire blends or inclusion of hydrophilic
      additives in the SSM was studied. The effect of ageing on some selected
      formulations was also evaluated, using scanning electron microscopy and
      differential thermal analysis. Twenty-one capsule formulations were prepared and
      assessed for their release characteristics. The mechanism of drug release from
      the test formulations was studied. The following results were obtained: a)
      Release data could not be correlated to the melting point (mp) of Gelucires used,
      pointing to relative lipophilicity of the base as a more important determinant of
      drug release. Among Gelucire grades having melting points higher than 37 degrees
      C, the release rate proved to be highly dependent on the HLB value and matrix
      composition. b) CBZ release occurred by different mechanisms, including matrix
      disintegration, diffusion and or erosion depending on the vehicle employed. c)
      Zero order release profiles of CBZ were obtained from SSM-based on G50/13, G53/10
      and their blends in ratios higher than 1:1 and G53/10 containing croscarmellose
      sodium. d) The ageing study revealed that these latter formulations, except those
      based on G50/13, also showed high dissolution stability during one year of shelf
      ageing. e) PVP, as a polymorphic transformation inhibitor, can be used to reduce
      the storage-induced changes of some grades of Gelucires. From the above data, it
      can be concluded that different grades of Gelucires and their blends as well as
      hydrophilic additives could be successfully used to formulate CBZ extended
      release SSM filled capsules with various release kinetics.

PMID- 15521329
TI  - Preliminary report of the discovery of a new pharmaceutical granulation process
      using foamed aqueous binders.
AB  - Spray granulation is commonly used to improve the flow of drug formulation
      powders by adding liquid binders. We have discovered a new granulation process
      whereby liquid binders are added as aqueous foam. Initial experiments indicate
      that foam granulations require less binder than spray granulations, less water is
      added to the powder mass, rates of addition of foam can be greater than rates of
      addition of sprayed liquids, and foam can be added in a single batch to the
      surface of the powder mass for incorporation at some later stage in the process.
      This new process appears to have no detrimental effects on granulate, tablet, or
      in vitro drug dissolution properties. In addition, the elimination of spray
      addition reduces the complexity of the process and avoids the plugging problems
      associated with spray nozzles. Several formulations were successfully scaled up
      from laboratory scale (1.5 kg) to pilot scale (15 kg). Process control was good
      and there was no detrimental effect on tablet and drug dissolution properties.
      This paper also proposes a working hypothesis of the mechanism by which foam
      granulation operates.

PMID- 15521330
TI  - Basic drug--enterosoluble polymer coevaporates: development of oral controlled
      release systems.
AB  - Precipitation of basic drugs within oral prolonged release systems, at the higher
      pH values of the intestine, would affect drug release. Coevaporates of a model
      basic drug verapamil HCl, in single or mixed polymer systems, containing Eudragit
      L100 (L100) and ethyl cellulose or Eudragit RS100, were prepared from ethanolic
      solution. XRD and DSC indicated loss of crystallinity of the drug in the
      coevaporates. The presence of the enterosoluble polymer in the system was found
      to aid in faster dissolution of the drug at higher pH values. This was affected
      by the presence and type of retarding polymer present in the system. Compression
      of the coevaporates resulted in either very slow release of the drug or
      undesirable changes in the release profile. Pelletization of a coevaporate
      containing drug and L100 yielded systems, which released the drug uniformly when
      studied by the buffer change method in simulated gastric (SGF) and intestinal
      (SIF) fluids. The presence of L100 in intimate contact with the drug was found to
      be essential for the desirable drug release properties of the system. The drug
      release occurred predominantly by diffusion in SGF and by a combination of
      diffusion and polymer dissolution/erosion in SIF. Appropriate choice of release
      modifiers and formulation variables and development of suitable formulations can
      yield systems which compensate for the reduced solubility of the drug in the
      higher pH environments of the intestine.

PMID- 15521331
TI  - Comparison of the TSI Model 3306 Impactor Inlet with the Andersen Cascade
      Impactor: solution metered dose inhalers.
AB  - The product performance of a series of solution Metered Dose Inhalers (MDIs) were
      evaluated using the TSI Model 3306 Impactor Inlet and the Andersen Cascade
      Impactor (ACI). The goal of the study was to test whether the fine particle and
      coarse particle depositions obtained using the Model 3306 were comparable to
      those results obtained by ACI testing. The analysis using the Model 3306 was
      performed as supplied by the manufacturer as well as with 20 cm and 40 cm
      vertical extensions that were inserted between the Model 3306 and the USP Inlet.
      Nine different solution formulations were evaluated. The drug concentrations
      ranged from 0.08 to 0.8% w/w and the ethanol cosolvent concentration varied
      between 5 and 20% w/w. In general, it was found that good correlations between
      the two instruments were obtained. However, for formulations containing 10-20%
      w/w ethanol it is shown that an extension fitted to the Model 3306 yielded an
      improved correlation to those obtained from the ACI.

PMID- 15521332
TI  - Oral absorption and pharmacokinetics of rebamipide and rebamipide lysinate in
      rats.
AB  - Rebamipide is an anti-ulcer agent exhibiting a low aqueous solubility and a poor
      oral bioavailability. This study was conducted to examine if the rebamipide
      lysinate salt form would exhibit improved solubility profiles and higher oral
      bioavailability compared with rebamipide free acid. Both compounds showed pH
      dependent solubility profiles, with the solubility of rebamipide lysinate
      dramatically improved at a median pH of 5.1 (17-fold increases) over free acid,
      but the improvement in the solubility was not as pronounced in artificial gastric
      and intestinal fluids (1.4- and 1.9-fold increases, respectively). The Cl, V(ss)
      and t1/2 in rats after i.v. injection of rebamipide (0.5 mg/kg) averaged 21.0 +/-
      3.2 ml/min/kg, 0.3 +/- 0.0 L/kg, and 0.4 +/- 0.1 hr, respectively. No significant
      difference was observed in these parameters between rebamipide and rebamipide
      lysinate. Despite improved solubility profiles, the absolute oral bioavailability
      of rebamipide lysinate was not increased (5.1 vs. 4.8%) nor did AUC (407.8 vs.
      383.6 ng x hr/ml) and C(max) (87.4 vs. 77.0 ng/ml) compared with rebamipide free
      acid. Rebamipide lysinate, however, showed a more rapid absorption, and initial
      serum drug concentrations were higher than those found for rebamipide free acid.

PMID- 15521333
TI  - Stabilization of rasburicase and physico-chemical characterization of the
      resulting injectable formulation.
AB  - Rasburicase (Fasturtec/Elitek) is a new generation of recombinant urate oxidase
      administred therapeutically by intravenous infusion for the prevention or
      treatment of hyperuricemia during chemotherapy. To ensure a long storage period,
      a freeze-dried formulation was developed to guarantee the molecular integrity and
      enzyme activity. Screening of potential excipients was the first stage of the
      preformulation study. The selection was based on stability results (rasburicase
      solution with excipient) obtained with the isoelectric focusing profiles and
      residual enzyme activity. The different excipients were classified as
      stabilising, neutral or destabilising. A stability study was then carried out on
      different freeze-dried formulations containing the usual bulking agents for
      freeze-drying, excipients with a high glass transition temperature or competitive
      enzyme inhibitors having a stabilising effect. A mannitol/alanine mixture in
      phosphate buffer was selected from these preliminary results. Finally, the
      optimal content of mannitol and alanine in the freeze-dried powder was determined
      by an experimental design study. The water content and the appearance of the
      "cake", the osmolality, pH, clarity, and enzyme activity of the reconstituted
      solution were assessed. The formula with a mannitol/alanine ratio of 0.7 was
      found to be the best composition. Differential scanning calorimetry and
      ThermoStimulated Current technique experiments were carried out to study the
      amorphous phase. A glass transition temperature of about 45-500 degrees C was
      found. Glassy state is known to preserve stability, which was verified by the
      real stability data. X-ray diffraction studies have shown that alanine is in a
      crystallised state and that mannitol remains amorphous. Crystallised excipients
      participate in forming the structure of the powder and therefore help to prevent
      any collapse. Amorphous mannitol creates a surrounding medium favourable to the
      stability of the protein.

PMID- 15521334
TI  - Is it the method or the process-separating the causes of low recovery.
AB  - During the development of a tablet formulation, a solvent capable of extracting
      100% of the drug from the tablet excipients must be identified as part of the
      analytical assay method. When a low drug recovery from a tablet is observed with
      the assay method, it must be determined whether a problem with the manufacturing
      process exists, or if the extraction of the drug was incomplete. A solvent screen
      study was conducted with CP-122,721 prototype formulations to select a robust
      solvent for the assay method. However, low tablet assay values (ca. 95%) were
      routinely observed during tablet formulation development and process scale up.
      Drug-excipient interactions in a variety of solvents were subsequently evaluated
      to confirm the selection of the extraction solvent as capable of 100% extraction.
      At this point the focus of the investigation was placed on process-related
      sources of low recovery, such as loss of drug to manufacturing equipment and/or
      segregation during the tableting process. The results suggest that the low drug
      recovery observed for the CP-122,721 tablets was due to segregation during the
      manufacture, while the selected extraction solvent was able to eliminate any
      interactions between CP-122,721 and the tablet excipients.

PMID- 15521335
TI  - Effect of formulation and process variables on the release behavior of
      amoxicillin matrix tablets.
AB  - The sustained release of amoxicillin is desired to be confined to the upper
      gastrointestinal tract to treat certain kind of infections. In vitro dissolution,
      at pH 1.2, of amoxicillin sustained release tablets has been studied varying the
      proportion of Carbopol 971P NF and sodium alginate as well as the ethanol/water
      proportion in the granulation fluid. M(t), the amount of drug released at time
      (t) and defined in terms of the total drug released over a long time period
      (M(inf), was described by M(t)/M(inf) = kt(n). Matrices with increasing
      proportions of sodium alginate showed increasing values of the exponent
      indicative of the release mechanism (n) and increasing release constant values
      (k). This is attributed to a drop in the coherence of the polymeric matrix with
      increasing alginate proportions that produces an increasing polymer relaxation
      and erosion. Decreasing Carbopol 971P NF proportions reduce the amount of
      dissolved polymer during granulation, producing a lesser obstruction of
      amoxicillin dissolution. Alginate proportions of 80% produce near zero order
      release profiles. Granules obtained with increasing ethanol proportions showed
      increasing release constant values and a minor change in the exponent (n) values.
      This is considered a result of lower polymer dissolution during granulation that
      allows a lesser matrix coherence and a greater amoxicillin dissolution. Alginate
      matrices granulated with different ethanol/water proportions showed no
      significant changes in the amoxicillin release profile. There is a trend toward
      increasing floating times with increasing Carbopol 971P NF proportions.

PMID- 15521336
TI  - Salaries keep pace, but are they enough for high-pressure jobs?

PMID- 15521337
TI  - Periop director positions harder to fill as talent pool is shrinking.

PMID- 15521338
TI  - Manager of year mentors the staff to lead.

PMID- 15521340
TI  - Hip and knee implant prices increase 9%.

PMID- 15521339
TI  - Should RNs be giving propofol in GI lab?

PMID- 15521341
TI  - ASC managers juggle competing demands.

PMID- 15521342
TI  - [Injury from fireworks and firecrackers during holidays].
AB  - BACKGROUND: Every year during the holidays of the Arab and Druze population, and
      especially during Id el-Adha, scores of injured from firecrackers, crackers,
      skyrockets and other homemade explosive devices arrive at the Western Galilee
      Hospital. Similar casualties present during the Jewish Purim Festival.
      OBJECTIVES: To characterize the population of the injured and to analyze various
      aspects of this kind of accidents, in order to reduce injury and minimize
      disability. METHODS: A retrospective survey of records of all injured from
      firecrackers and similar devices during holidays that arrived at our hospital
      between 1999 and 2003 was conducted. Between 2001 and 2002 the trauma team, in
      cooperation with the local leadership, directed an education and information
      campaign in the community, in an attempt to reduce these injuries. RESULTS:
      During the study period, a decrease in the rate of injury was observed, which in
      the year 2003, reached a level of 50% of the 1999 figures. Of the injured, 53%
      were children (< or = 15 years old), 93% were Arab or Druze, and 93% were males.
      The rate of injuries from fireworks in 2003 was significantly lower than the mean
      rate of the years 1999, 2001, 2002 (p=0.045). The major cause of injury was
      firecrackers (67%) followed by fireworks (21%). Major injuries were to the
      extremities (58%), followed by facial and eye trauma (24%) and burns (11%). Of
      the casualties, 54% were lightly injured, 46% were hospitalized, 24% required
      surgical intervention and 7% lost fingers. Two individuals lost eyesight in one
      eye, but no fatalities occurred. CONCLUSIONS: The reduced rate of injury from
      fireworks and similar devices can be attributed to two major reasons:
      intervention by the trauma team and enforcement by the police and the Ministry of
      Trade and Industry. We recommend conducting a combined campaign of education and
      parental guidance with the involvement of community leaders and local media, and
      to increase law-enforcement. The organization of central firework displays in
      each community during this holiday should be considered.

PMID- 15521343
TI  - [Evaluation of hospital admissions: admission guidelines implementation in a
      pediatric emergency department].
AB  - OBJECTIVES: To develop and implement locally tailored pediatric admission
      guidelines for use in a pediatric emergency department and evaluate the
      appropriateness of admissions based on these guidelines. METHODOLOGY: Our Study
      was based on the development of admission guidelines by senior physicians, using
      the Delphi Consensus Process, for use in the Pediatric Emergency Department (PED)
      at Soroka University Medical Center (Soroka). We evaluated the appropriateness of
      admissions to the pediatric departments of Soroka on 33 randomly selected days in
      1999 and 2000 prior to guideline implementation and 30 randomly selected days in
      2001, after guideline implementation. A total of 1037 files were evaluated.
      FINDINGS: A rate of 12.4% inappropriate admissions to the pediatric departments
      was found based on locally tailored admission guidelines. There was no change in
      the rate of inappropriate admissions after implementation of admission guidelines
      in PED. Inappropriate admissions were associated with age above 3 years, hospital
      stay of two days or less and the season. The main reasons for evaluating an
      admission as inappropriate were that the admission did not comply with the
      guidelines and that the case could be managed in an ambulatory setting. There
      were distinctive differences in the characteristics of the Bedouin and Jewish
      populations admitted to the pediatric departments, although no difference was
      found in the rate of inappropriate admissions between these populations.
      CONCLUSIONS: Patient management in Soroka PED is tailored to the conditions of
      this medical center and to the characteristics of the population it serves. The
      admission guidelines developed reflect these special conditions. Lack of change
      in the rate of inappropriate admissions following implementation of the
      guidelines indicates that the guidelines reflect the physicians' approach to
      patient management that existed in Soroka PED prior to guideline implementation.
      Hospital admission guidelines have a role in the health management system;
      however, these guidelines must be tailored to reflect local characteristics and
      needs.

PMID- 15521344
TI  - [Breast reconstruction with deep inferior epigastric perforator artery free
      flap].
AB  - Today, breast reconstruction is an integrate part of the treatment for patients
      after ablative breast surgery. Many techniques of breast reconstruction were
      developed utilizing autologous tissues. Some of these techniques involve
      significant donor site morbidity, making their use questionable. We present our
      initial experience using the Deep Inferior Epigastric Artery (DIEA) Perforator
      Free Flap for breast reconstruction. The flap carries the skin and fat tissue
      from the abdominal wall while maintaining and preserving the abdominal wall
      muscles and using only it's vascular pedicle, which is re-anastomosed of the
      vessels on the thorax. This procedure was used in 50 women, with full success in
      49 cases. There were only a few complications, most of which were treated
      conservatively. This technique of breast reconstruction holds many advantages:
      shorter recovery period, less pain, rapid return to normal activity, maintenance
      of the abdominal wall strength and easier insetting of the reconstructed breast
      with better aesthetic results.

PMID- 15521345
TI  - [Psychiatric examination performed by phone to determine guardianship--is it
      legally valid?].
AB  - BACKGROUND: The administration of a psychiatric evaluation to determine
      guardianship entails the prerequisite of a full psychiatric examination of the
      patient. In psychogeriatrics, dementia is the common reason for measures to
      determine incompetence and guardianship and in general psychiatry it is
      applicable for the diagnosis of schizophrenia. Legal guardianship is determined
      by the court and can apply to aspects involving confidentiality such as the
      patient's assets or body or both, and its duration can be temporary or permanent.
      This is a case study of a 30 year old man who had never undergone a psychiatric
      examination. His parents reported behavior that was suggestive of a prolonged
      paranoid psychotic state for the past 8 years with deterioration in the last
      year. All attempts by his parents to bring him to a medical or psychiatric
      examination were refused by the patient. In order to prevent further
      deterioration of the situation, the family was advised to request legal
      guardianship for him. Due to his refusal to be examined and the lack of
      indication for a forced examination, a long taped phone conversation was
      conducted with the patient and later validated to ensure that this was the
      patient in question. This conversation together with heteroanamnesis, provided
      the basis for writing a psychiatric evaluation recommending the appointment of a
      legal guardian for the patient. To the best of our knowledge, the court's
      decision to appoint a legal guardian based on a telephone conversation is a
      precedent.

PMID- 15521346
TI  - [A prospective, randomized double-blind study on the treatment of anal fissures
      with Nitroglycerin ointment].
AB  - BACKGROUND: Anal fissure is a common disease. Treatment includes conservative
      measures or surgery. One of the treatment options is topical Nitroglycerin
      ointment. MATERIALS AND METHODS: We present a prospective, randomized, double
      blind study, encompassing 48 patients suffering from chronic anal fissure. The
      subjects were divided into three groups according to the dose of Nitroglycerin
      ointment received--group I--0% (placebo), group II--0.2% (0.75 mg) and group III-
      0.4% (1.5 mg). Demographic data, medical history and physical findings were
      recorded. Healing, pain relief and adverse events were evaluated during and after
      the treatment period. RESULTS: No significant difference (p<0.05) was found
      between the groups with respect to patient age, gender, past history, physical
      examination, amount of ointment used and adverse events. Thirty three of the 48
      (69%) patients completed the study. No significant differences were found between
      the groups with respect to the reasons and rates of leaving the study (p=0.494).
      Fifteen patients failed to complete the study; eight patients (17%) due to
      headaches, one patient was operated upon and six patients left the study because
      of cooperation problems. No significant difference was found between the groups
      regarding healing (p=0.952) or pain relief (p=0.458-0.8 according to the type of
      pain checked). CONCLUSIONS: According to our study, there was no benefit
      regarding healing or pain relief, in treating patients suffering from an anal
      fissure with Nitroglycerin ointment in combination with stool softeners and sitz
      baths, compared to the same treatment without Nitroglycerin ointment.

PMID- 15521347
TI  - [From the Natanyahu State Commission to management tasks in the Israeli health
      system].
AB  - BACKGROUND: Ben-Gurion University (BGU) in Beer Sheva inaugurated a special
      training program for junior academic administrative personnel to improve the
      quality of service in health care organizations through suitable and high-quality
      administration. The program, the first of its kind in Israel, has been in
      operation since 1994 and prepares 50 candidates annually for administrative
      positions within the health system, or a total of 224 graduates to date. The
      program was founded on the recommendations of a state commission established in
      1990 and headed by retired Supreme Court Justice Shoshana Natanyahu (The
      Natanyahu Commission, 1990). The commission was appointed to examine the
      performance of the health system in Israel and recommend reforms and changes that
      would improve the quality and efficiency of health services and the overall
      performance of the system. AIM: This study examined the integration of graduates
      of the undergraduate program in Health Systems Management (HSM) within the
      private and public health system in Israel, including employment trends and a
      retrospective evaluation of the program. METHODS: Within the framework of the
      study, questionnaires were sent to all graduates of the program. Participants
      were requested to answer questions regarding their present place of employment,
      their satisfaction with their academic degree, how they found employment, and so
      forth. RESULTS: The research results show that 59% of the graduates of the HSM
      department at BGU who responded to the questionnaire, worked in the health system
      upon completion of their studies, and in 2002--at the time of the survey--42% of
      all graduates were currently employed within the health system. Most of the
      graduates who entered the system and remained within the system, were women: out
      of 46 graduates working in the health system today, 38 (83%) are women. It should
      be noted that while there is some migration of graduates to work in other systems
      and sectors of the economy, 78% of the respondents believe that the degree
      program in HSM is justified. Apparently, according to the study, although the
      health system needs graduates, it does not always know how, or does not always
      want to or finds difficulty in absorbing the graduates and effectively utilizing
      their skills to meet the needs of the system. CONCLUSIONS: The data reveals that
      graduates of the undergraduate program in HSM have integrated well into the
      health system, but not as well as may have been expected. The graduates
      encountered difficulties in their absorption into management roles in the public
      health system and felt that the extent of their abilities has yet to be fully
      recognized and utilized by the system.

PMID- 15521348
TI  - [What is the actual lesson from the WHI study upon its completion?].
AB  - The issue of hormone replacement therapy (HRT) in postmenopausal women has been
      influenced recently by negative attitudes of the media and health authorities,
      based on misinterpretation of the results of the Women's Health Initiative (WHI).
      This atmosphere led to the discontinuation of HRT in women with menopausal
      symptoms, because of fear and anxiety created by overestimated harmful effects of
      hormones. Careful evaluation of the data in the estrogen-progestin arm shows that
      the reported risk for breast cancer and cardiovascular events was at the most
      minute, in the order of 0.1% (1 thousandth) excess in risk for every year of use.
      No risk was observed for women younger that 60 years of age. Preliminary data of
      the estrogen-only arm points at a non-significant reduction in risk for both
      coronary events and breast cancer. While the WHI study recruited women in their
      late 60's who were assigned to receive a standard dose of HRT, the typical woman
      who seeks consultation at the menopause clinic is much younger in age and usually
      suffers from menopause symptoms. Therefore, the results of the WHI study simply
      do not apply to the usual clinical set-up at the menopause clinic in Israel.

PMID- 15521349
TI  - [Multiple sclerosis and anti-phospholipid syndrome--one or two diseases?].
AB  - Multiple sclerosis is an autoimmune central nervous system disease that affects
      young adults and causes inflammation, demyelination and axonal loss. Within the
      common relapsing-remitting course of the disease patients develop various
      neurological symptoms that lead to significant disability overtime. The anti
      phospholipid syndrome, similarly to multiple sclerosis, appears in young adults
      and is characterized by thromboembolic events and pregnancy complications. The
      overlay between these two diseases and the ability to correctly diagnose or
      differentiate between them is sometimes difficult. The current review approaches
      this problem and discusses whether multiple sclerosis and anti-phospholipid
      syndrome are actually one or two diseases.

PMID- 15521350
TI  - [Small bowel malignancies: why are they so rare?].
AB  - Cancer of the small-bowel is rare and comprises 2.4% of gastrointestinal
      malignancies. This is despite of its large mucosal surface area and its location
      between the stomach and the large bowel, two of the most common cancer sites.
      Nevertheless, there is a similarity between the disease and colorectal cancer.
      Therefore, it is of great interest to study the protective mechanisms of this
      organ and how tumor arises when these protectors fail. Among the risk factors for
      small bowel malignancies are Inflammatory Bowel Disease (IBD), familial
      syndromes, and lifestyle parameters (alcohol consumption, smoking, and high fat
      and animal protein diet). Due to the unusual symptoms, the rarity of the disease,
      and the difficulty in small bowel imaging, a correct diagnosis is often delayed.
      The treatment of choice, which allows full recovery, as in other malignancies of
      the gastrointestinal tract, is surgical resection of the tumor.

PMID- 15521351
TI  - [Trauma in pregnancy].
AB  - Trauma is the leading non-obstetric cause of maternal death. Whereas maternal
      mortality and morbidity due to obstetrical reasons are decreasing, those related
      to trauma, mainly motor vehicle accidents, are increasing. Knowledge and
      awareness of normal physiological changes during pregnancy and the unique
      response to stress and trauma, is essential for all caregivers treating trauma
      patients. Key points for appropriate changes in various systems and their
      relevant application for diagnosis, treatment and resuscitation approaches are
      presented. Peri-mortem cesarean section, although rarely required, is discussed.
      Preventive measures in pregnancy, especially the use of seat belts, are
      emphasized.

PMID- 15521352
TI  - [Hip arthroscopy--indications, surgical technique and implementation].
AB  - Hip arthroscopy was first described by Burman in 1931. During the 1980's this
      procedure was performed by a limited group of orthopedic surgeons. Implementation
      and development of the surgical procedure received most attention during those
      years, together with the formulation of specific indications to perform hip
      arthroscopy. In contrast to other large joints (knee, shoulder), where accurate
      diagnosis is feasible using standard imaging procedures such as plain
      radiographs, computed tomography and magnetic resonance imaging, the hip joint
      often presents as a diagnostic anomaly. In specific cases hip arthroscopy can add
      invaluable information, which, in correlation with the symptoms of the patient,
      can lead to an accurate diagnosis. Hip arthroscopy has various indications
      including the removal of foreign or loose bodies, irrigation of an infected hip
      joint and evaluation of the cartilage. The list of indications is still expanding
      as more surgeons become familiar with the technique. Hip arthroscopy is a safe
      and efficient procedure in experienced hands. This review of the literature
      describes the surgical procedure, various clinical situations, indications and
      the therapeutic potential of hip arthroscopy.

PMID- 15521353
TI  - [Carpal tunnel syndrome].
AB  - Carpal tunnel syndrome is the most common peripheral nerve compression syndrome.
      Compression of the median nerve in the carpal tunnel, disrupts the blood-nerve
      barrier causing edema, inflammation and fibrosis of its surrounding connective
      tissues. In the next stage of the syndrome there is a disruption of the myelin
      coverage of the nerve followed by damage to the axons. Most carpal tunnel
      syndromes are idiopathic. Other causes include intrinsic factors (which cause
      pressure within the tunnel), extrinsic factors (which cause pressure from outside
      the tunnel) and overuse/exertional factors. Patients usually report numbness and
      pain of the palmar aspect of their 1st, 2nd, 3rd and radial half of their 4th
      finger, night pain and gradual worsening of their symptoms. At a later stage,
      weakness and atrophy of the thenar muscles appears. The physical examination may
      show a decrease in sensibility, positive provocative tests and a decrease in
      thenar strength. The typical finding in the nerve conduction tests is a prolonged
      latency period. The conservative treatment for carpal tunnel syndrome includes
      ergonomic modifications, anti inflammatory medications and splintage and less
      frequently, special exercise and therapeutic ultrasound. The indications for
      operative treatment are failure of conservative treatment or severe carpal tunnel
      syndrome. The purpose of the operation is to relieve the pressure in the carpal
      tunnel by dissecting the transverse ligament. The operation can be done in an
      open approach, endoscopic approach or limited invasive approach.

PMID- 15521354
TI  - [The information age and its effect on the doctor-patient relationship].
AB  - A variety of reasons can explain the paternalistic relationship between doctor
      and patient that prevailed for centuries. Undoubtedly, the exclusive control
      exercised by doctors over medical knowledge, constitutes a primary reason for the
      perpetuation of this relationship. However, in the past few generations,
      substantial changes have evolved in the nature of the physician-patient
      encounter. For example, the concept of "informed consent", introduced by social
      and legal changes, has subsequently led to the empowerment of the patient.
      Furthermore, the current information revolution might well bring about even more
      substantial changes in the doctor-patient relationship. In this article we will
      discuss the principal changes that have occurred in the doctor-patient
      relationship due to the information revolution, and explore future trends which
      might be expected in view of these changes.

PMID- 15521355
TI  - [Hormone replacement therapy in breast cancer survivors: the Israeli Society for
      Clinical Oncology and Radiotherapy policy letter].
AB  - The Israeli Society for Clinical Oncology and Radiotherapy appointed experts in
      breast cancer therapy to assess the Society's policy regarding hormone
      replacement therapy (HRT) in breast cancer survivors with menopausal symptoms.
      The first policy letter was published in November 2002, and referred to available
      literature at that time which included retrospective data alone. The professional
      literature suggested no increased risk in breast cancer recurrence or cancer
      specific mortality, and no effect on overall survival with the use of HRT for a
      limited period (up to 3 years). This data served as the rationale for
      international prospective studies. Former committee recommendations and
      precautions are detailed in the original publication. In February 2004, the
      interim analysis of a prospective trial, the HABIT (Hormonal replacement therapy
      after breast cancer--is it safe?) was published. In that trial, breast cancer
      survivors with menopausal symptoms were randomized to HRT (estrogens with or
      without progestins) or no therapy for 2 years. A total of 434 women were
      recruited from centers in Scandinavia who participated with the International
      Breast Cancer and the European Organization for Research and Treatment groups.
      Analysis was restricted to 345 women with at least one follow up report; median
      follow-up period was 2.1 years. The relative risk for breast cancer event was 3.5
      (95% C.I. 1.5-8.1) in HRT users as compared with the non-HRT group and the HABIT
      trial was terminated. Study limitations are discussed. Thereby, at this time HRT
      can no longer be considered safe in breast cancer survivors. Physicians treating
      breast cancer survivors for severe menopausal symptoms should present study
      results and alternative non-hormonal treatment options to allow patients
      optimized consented treatment decisions.

PMID- 15521356
TI  - [Geriatrics 2004].

PMID- 15521357
TI  - D1-like dopamine receptor-mediated function in congenic mutants with D1 vs. D5
      receptor "knockout".
AB  - Current understanding of the functional roles of individual dopamine D1-like [D1,
      D5] and D2-like [D2L/s, D3, D4] receptor subtypes remains incomplete. In
      particular, the lack of pharmacological agonists and antagonists able to
      distinguish between D1 and D5 receptors means that any differential roles in the
      regulation of behavior are poorly understood. Mutant mice with targeted gene
      deletion ("knockout") of individual dopamine receptor subtypes offer an important
      alternative approach to resolving these functional roles. In congenic D1 mutants
      examined ethologically, progressive increases in specific topographies of
      behavior over wildtypes were considerably greater than those in D1 mutants on a
      mixed genetic background; D1 knockout appears to influence the neuronal
      substrate(s) of habituation to disrupt sculpture of the changing topography of
      behavior from initial exploration through to quiescence. Similarly, the D1
      receptor appears to regulate specific topographies of orofacial movement in the
      mouse as these are "sculpted" in a time-dependent manner. Although the well
      recognized role of the D1-like family in regulating several aspects of behavioral
      topography has been assumed to involve primarily D1 receptors, this presumption
      may require modification to accommodate a subtle but not negligible role for
      their D5 counterparts as evidenced in the phenotype of congenic D5 mutants.

PMID- 15521358
TI  - Signaling mechanisms of the D3 dopamine receptor.
AB  - A substantial body of evidence shows the capacity of the dopamine D3 receptor to
      couple functionally to G proteins when expressed in an appropriate milieu in
      heterologous expression systems. In these systems, activation of D3 receptors
      inhibits adenylate cyclase, modulates ion flow through potassium and calcium
      channels, and activates kinases, most notably mitogen-activated protein kinase.
      Coupling to Gi/Go is implicated in many of these effects, but other G proteins
      may contribute. Studies with chimeric receptors implicate the third intracellular
      loop in the mediation of agonist-induced signal transduction. Finally, D3
      preferring drugs modulate expression of c-fos in neuronal cultures and brain.
      Signaling mechanisms of the D3 receptor in brain, however, remain to be
      definitively determined.

PMID- 15521359
TI  - Dopamine D4 receptors: beyond schizophrenia.
AB  - Dopamine D4 receptors mediate a wide range of neuronal signal transduction
      cascades. Malfunctions of these mechanisms may contribute to the pathophysiology
      of neuropsychiatric disorders, and their modification underlies the actions of
      many psychotropic drugs. Postmortem neuropathological and genetic studies provide
      inconclusive associations between D4 receptors and schizophrenia. Clinical trials
      of partially selective lead D4 antagonists have proved them to be ineffective
      against psychotic symptoms in patients diagnosed with schizophrenia. However,
      associations are emerging between D4 receptors and other neuropsychiatric
      disorders, including attention-deficit hyperactivity disorder as well as specific
      personality traits such as novelty seeking. Preclinical studies indicate that D4
      receptors play a pivotal role in the cellular mechanisms of hyperactivity,
      impulsivity, and working memory. Accordingly, D4 receptors have broader
      implications for human illnesses than has been suggested by early focus on
      psychotic illness as a clinical target, and selective D4 agents may yield
      clinically useful drugs for several neuropsychiatric disorders that require
      improved treatments.

PMID- 15521360
TI  - D5 dopamine receptor knockout mice and hypertension.
AB  - Abnormalities in dopamine production and receptor function have been described in
      human essential hypertension and rodent models of genetic hypertension. All of
      the five dopamine receptor genes (D1, D2, D3, D4, and D5) expressed in mammals
      and some of their regulators are in loci linked to hypertension in humans and in
      rodents. Under normal conditions, D1-like receptors (D1 and D5) inhibit sodium
      transport in the kidney and the intestine. However, in the Dahl salt-sensitive
      and spontaneously hypertensive rats, and humans with essential hypertension, the
      D1-like receptor-mediated inhibition of sodium transport is impaired because of
      an uncoupling of the D1-like receptor from its G protein/effector complex. The
      uncoupling is genetic, and receptor-, organ-, and nephron segment-specific. In
      human essential hypertension, the uncoupling of the D1 receptor from its G
      protein/effector complex is caused by an agonist-independent serine
      phosphorylation/desensitization by constitutively active variants of the G
      protein-coupled receptor kinase type 4. The D5 receptor is also important in
      blood pressure regulation. Disruption of the D5 or the D1 receptor gene in mice
      increases blood pressure. However, unlike the D1 receptor, the hypertension in D5
      receptor null mice is caused by increased activity of the sympathetic nervous
      system, apparently due to activation of oxytocin, V1 vasopressin, and non-N
      methyl D-aspartate receptors in the central nervous system. The cause of the
      activation of these receptors remains to be determined.

PMID- 15521361
TI  - Dopamine receptor signaling.
AB  - The D1-like (D1, D5) and D2-like (D2, D3, D4) classes of dopamine receptors each
      has shared signaling properties that contribute to the definition of the receptor
      class, although some differences among subtypes within a class have been
      identified. D1-like receptor signaling is mediated chiefly by the heterotrimeric
      G proteins Galphas and Galphaolf, which cause sequential activation of adenylate
      cyclase, cylic AMP-dependent protein kinase, and the protein phosphatase-1
      inhibitor DARPP-32. The increased phosphorylation that results from the combined
      effects of activating cyclic AMP-dependent protein kinase and inhibiting protein
      phosphatase 1 regulates the activity of many receptors, enzymes, ion channels,
      and transcription factors. D1 or a novel D1-like receptor also signals via
      phospholipase C-dependent and cyclic AMP-independent mobilization of
      intracellular calcium. D2-like receptor signaling is mediated by the
      heterotrimeric G proteins Galphai and Galphao. These pertussis toxin-sensitive G
      proteins regulate some effectors, such as adenylate cyclase, via their Galpha
      subunits, but regulate many more effectors such as ion channels, phospholipases,
      protein kinases, and receptor tyrosine kinases as a result of the receptor
      induced liberation of Gbetagamma subunits. In addition to interactions between
      dopamine receptors and G proteins, other protein:protein interactions such as
      receptor oligomerization or receptor interactions with scaffolding and signal
      switching proteins are critical for regulation of dopamine receptor signaling.

PMID- 15521362
TI  - Dopamine receptor microdomains involved in molecular recognition and the
      regulation of drug affinity and function.
AB  - A cationic protonatable amine moiety on dopaminergic ligands forms a high
      affinity reinforced ionic bond with an anionic aspartic acid at position 3.32 of
      dopamine receptors. When present, catechol hydroxyls of the ligands form hydrogen
      bonds with serines at position 5.42, 5.43, and 5.46, and this network of hydrogen
      bonds serves to orient ligands in the binding-site crevice and increase their
      binding affinity. A steric clash between aromatic moieties of the ligands and
      aromatic amino acids of the receptor (e.g., H6.55, F6.52 or F6.51 and W6.48) is
      likely to be propagated in domino-like fashion along the length of TM6, which is
      believed to trigger activation of the receptor. Specifically, it is the change in
      the conformation of W6.48 from an orientation perpendicular to the plane of the
      lipid membrane to one that is parallel that is believed to result in activation.
      Molecular determinants that mediate the D4/D2-selectivity of many extremely D4
      selective 1,4-DAP ligands, include a nonconserved cluster of bulky amino acids at
      the TM2/TM3 interface (positions 2.61, 3.28 and 3.29).

PMID- 15521363
TI  - Penicillium.

PMID- 15521364
TI  - Can we diagnose atopy with a laboratory test?

PMID- 15521365
TI  - Determinants of asthma and its clinical course.
AB  - OBJECTIVE: To examine factors that influence the natural history of asthma, such
      as genetics, atopy, air pollution and environmental tobacco smoke,
      gastroesophageal reflux, and infection, to promote early identification and
      treatment of patients at risk for persistent asthma. DATA SOURCES: Journal
      articles published in English involving human subjects with asthma. STUDY
      SELECTION: Studies were selected for their relevance to the discussion of asthma
      and the factors that contribute to its persistence. Epidemiologic studies were
      favored in assessing the natural history of asthma from childhood to adulthood.
      RESULTS: Major factors that can influence the severity and persistence of asthma
      are genetics, atopy, pollution, environmental tobacco smoke, gastroesophageal
      reflux, and respiratory infections. Epidemiologic studies reveal that factors
      strongly linked to the persistence of childhood asthma into adult life are early
      age of disease onset with more severe symptoms, atopy, and level of allergen
      exposure. CONCLUSIONS: Although there is still much research to be done,
      epidemiologic studies have repeatedly proven that the natural history of asthma
      is in some ways predictable. Early identification of patients at risk for
      persistent asthma, combined with early institution of pharmacologic and
      nonpharmacologic intervention strategies, may lead to better outcomes.

PMID- 15521366
TI  - Persistent dyspnea and chest pain in a 26-year-old woman with asthma.

PMID- 15521367
TI  - Differential diagnosis of IgE-mediated allergy in young children with wheezing or
      eczema symptoms using a single blood test.
AB  - BACKGROUND: Allergy-like symptoms are common in young children, but the case
      history and physical examination cannot identify the underlying origins of
      overlapping symptom profiles. OBJECTIVE: To evaluate a blood test, Phadiatop
      Infant (Pharmacia Diagnostics AB, Uppsala, Sweden), for differentiating the
      capability of IgE-mediated disease in young children with recurrent wheezing,
      eczema, or both. METHODS: One hundred forty-seven children (mean age, 2.0 years)
      were consecutively referred to 2 allergy centers by their primary care physician
      for recurrent wheezing, eczema, or both. The allergist's clinical evaluation
      included medical history, physical examination, skin prick testing with inhalant
      and food allergens, and specific IgE determinations in blood. The accuracy of
      Phadiatop Infant was evaluated in a masked manner against the allergist's final
      diagnosis. RESULTS: Sixty-nine children had wheezing, 69 had eczema, and 9 had
      both symptoms. Sixty-one children were clinically diagnosed as having IgE
      mediated allergy, 78 as having non-IgE-associated disease, and 8 as having an
      inconclusive diagnosis. Fifty-six of the 61 children with IgE-mediated allergy
      had positive Phadiatop Infant test results, and 64 of 78 without the condition
      had negative results. Sensitivity was 92% and specificity was 82%, with positive
      and negative predictive values of 80% and 93%, respectively. Thirteen children
      with a positive Phadiatop Infant test result and a negative final diagnosis were
      retested after 2 years; 12 of them were diagnosed as having IgE-mediated allergy
      using a masked evaluation. CONCLUSIONS: The Phadiatop Infant blood test
      discriminates between IgE- and non-IgE-mediated symptoms in children younger than
      4 years.

PMID- 15521368
TI  - Correlation between age and allergens in pediatric atopic dermatitis.
AB  - BACKGROUND: There has been significant progress recently in the clinical
      investigation of atopic dermatitis (AD), especially in the recognition of
      aeroallergens as aggravating factors in AD. However, sensitization to food
      allergens and aeroallergens in children with AD has not been fully studied.
      OBJECTIVE: To evaluate the correlation between age and allergens in children with
      AD. METHODS: A retrospective cross-sectional study was performed between January
      1, 1999, and December 31, 2002, on 262 children with a definitive diagnosis of AD
      aged 0 to 16 years. Comparison of 3 age groups (<2 years, 2-5 years, and >5
      years) with the correlation of food allergens and aeroallergens using the CAP
      FEIA test was made using linear regression and logistic regression analyses.
      RESULTS: In children younger than 2 years, AD was associated with food allergens.
      In children aged 2 to 5 years, both food allergens and aeroallergens played an
      important role. In children older than 5 years, only elevated aeroallergen
      specific IgE levels were noted (P < .02). Age correlated negatively with food
      allergens and positively with aeroallergens after adjusting for sex (P < .04).
      Sensitization to aeroallergens may correlate with acquisition of the respiratory
      symptoms of the atopic state. CONCLUSIONS: Food allergens may be the major
      trigger of AD in early life, after which the role of environmental aeroallergens
      become more important and may be associated with respiratory sensitization.

PMID- 15521369
TI  - Safety of high-dose rofecoxib in patients with aspirin-exacerbated respiratory
      disease.
AB  - BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is characterized by
      progressive sinusitis, nasal polyposis, and asthma that begins and continues in
      the absence of exposure to aspirin and nonsteroidal anti-inflammatory drugs
      (NSAIDs). Cross-sensitivity to all NSAIDs that inhibit cyclooxygenase-1 (COX-1)
      occurs in these individuals. Reactions to aspirin and NSAIDs in patients with
      AERD are largely due to inhibition of COX-1. Despite accumulating data on the
      safety of COX-2 selective inhibitors in AERD, concern still remains that high
      doses of a COX-2 inhibitor may be sufficient to induce a cross-reaction.
      OBJECTIVE: To determine whether high-dose rofecoxib cross-reacts in patients with
      AERD and asthma. METHODS: Sixty asthmatic patients underwent blinded placebo
      controlled oral challenges with 50 mg of rofecoxib. Aspirin sensitivity was
      subsequently confirmed in all patients with the use of single-blinded aspirin
      challenges. RESULTS: None of the 60 patients experienced any symptoms, changes in
      nasal examination results, or declines in lung function during rofecoxib
      challenge. All 60 patients experienced respiratory reactions to aspirin
      challenge, with a mean provoking dose of 57 mg. The exact 1-sided 95% confidence
      interval for the underlying probability of 50 mg of rofecoxib inducing
      respiratory cross-reactions in patients with AERD is 0 to 0.05, or 0% to 5%.
      CONCLUSIONS: These results confirm the lack of cross-reactivity of aspirin and
      the highly selective COX-2 inhibitors in AERD. We suggest that it is time for the
      labeling of highly selective COX-2 inhibitors to reflect these data and for the
      warning that patients with AERD in particular and asthmatic patients in general
      avoid selective COX-2 inhibitors to be removed.

PMID- 15521370
TI  - Patient preferences for sensory attributes of intranasal corticosteroids and
      willingness to adhere to prescribed therapy for allergic rhinitis: a conjoint
      analysis.
AB  - BACKGROUND: Sensory attributes of intranasal corticosteroid (INS) products vary.
      OBJECTIVE: To evaluate patient preferences for INS sensory attributes and the
      degree to which attributes influence patients' willingness to adhere to therapy.
      METHODS: We conducted a cross-sectional study with 120 individuals across 4 US
      allergy/immunology clinics. Respondents chose between pairs of hypothetical INSs
      differing in sensory attribute composition. We measured the strength of
      preferences for 6 sensory attributes (smell, taste, aftertaste, throat rundown,
      nose runout, and feel of spray in nose or throat). Preferences were measured for
      3 intensity levels of each sensory attribute (eg, no taste, weak taste, and
      strong taste). Other outcomes included an importance score for each sensory
      attribute and patients' willingness to adhere to therapy with an INS with the
      lowest intensity levels of each sensory attribute vs one with moderate intensity
      levels. RESULTS: Preferences decreased with increasing intensity levels of each
      sensory attribute. Aftertaste was the most important attribute in 28% of
      patients, taste in 19%, throat rundown in 18%, nose runout in 12%, smell in 11%,
      and feel of spray in 7%. If instructed to take an INS daily for 3 months, 77% of
      patients stated that they would definitely be able to follow their physician's
      advice (willingness to adhere) if given one containing the lowest level of each
      sensory attribute vs 4% if given one having moderate levels (P < .01).
      CONCLUSIONS: Patient preferences are inversely related to increasing intensity
      levels of sensory attributes and affect patients' willingness to adhere to
      therapy. Application of patient preferences when selecting INSs could improve
      adherence.

PMID- 15521371
TI  - Fluticasone propionate and salmeterol administered via Diskus compared with
      salmeterol or fluticasone propionate alone in patients suboptimally controlled
      with short-acting beta2-agonists.
AB  - BACKGROUND: Optimal therapy for many patients with persistent asthma requires
      control of both main components of this disease: inflammation and
      bronchoconstriction. OBJECTIVES: To compare the efficacy and safety of initiating
      maintenance therapy with an inhaled, long-acting beta2-agonist and an inhaled
      corticosteroid administered from a single device with that of the individual
      agents alone. METHODS: A 12-week, randomized, double-blind study was conducted in
      patients 12 years and older with persistent asthma who were symptomatic while
      taking as-needed, short-acting beta2-agonists alone. Treatments were administered
      twice daily via the Diskus device: salmeterol, 50 microg; fluticasone propionate,
      100 microg; or fluticasone propionate, 100 microg, with salmeterol, 50 microg.
      RESULTS: Of 555 patients screened, 267 were randomly assigned to treatment. At
      end point, fluticasone propionate and salmeterol significantly increased predose
      forced expiratory volume in 1 second (FEV1) compared with salmeterol alone (0.51
      +/- 0.05 L vs 0.38 +/- 0.04 L, P = .04). Fluticasone propionate and salmeterol
      significantly increased area under the serial FEV1 curve at treatment week 12
      relative to predose FEV1 (baseline) on treatment day 1 (AUCb1, 8.4 +/- 0.6 L/h; P
      < or = .02) compared with salmeterol (6.2 +/- 0.5 L/h) and fluticasone propionate
      (7.0 +/- 0.6 L/h). Fluticasone propionate and salmeterol were significantly (P <
      or = .02) more effective than the individual agents used alone in improving
      morning and evening peak expiratory flow rate and asthma symptoms. In addition,
      fluticasone propionate and salmeterol effectively reduced rescue albuterol use (P
      < or = .04). All treatments were well tolerated. CONCLUSIONS: In patients
      symptomatic while taking short-acting beta2-agonists alone, initial maintenance
      treatment of the 2 main components of asthma, inflammation and smooth muscle
      dysfunction, with fluticasone propionate and salmeterol, 100 and 50 microg,
      administered via the Diskus results in greater improvements in overall asthma
      control compared with treatment of either component alone.

PMID- 15521372
TI  - Safety of the new selective cyclooxygenase type 2 inhibitors rofecoxib and
      celecoxib in patients with anaphylactoid reactions to nonsteroidal anti
      inflammatory drugs.
AB  - BACKGROUND: Controlled oral challenge with nonsteroidal anti-inflammatory drugs
      (NSAIDs) is the only definite way to detect safe NSAIDs in patients with NSAID
      induced anaphylactoid reactions. OBJECTIVE: To evaluate the safety of the
      selective cyclooxygenase (COX) type 2 inhibitors rofecoxib and celecoxib in
      patients with single-reactive, NSAID-induced anaphylactoid reactions. METHODS: We
      prospectively conducted single-blind, placebo-controlled oral challenges
      (SBPCOCs) with rofecoxib and celecoxib in 33 patients with single-reactive, NSAID
      induced anaphylactoid reactions. RESULTS: Nineteen women and 14 men (age range,
      20-78 years; mean age, 44.8 years) exhibited anaphylactoid reactions on emergency
      department admission. Symptoms involved the skin (100%), laryngeal edema (73%),
      systolic hypotension (39%), and the gastrointestinal system (15%). The NSAIDs
      most frequently involved in the episodes were dipyrone (64%), propyphenazone
      (12%), and diclofenac (12%). In all patients, tolerance to a potent,
      nondiscriminatory COX inhibitor (except those reported as being responsible for
      the reaction) was noted. The SBPCOCs with the selective COX-2 inhibitors
      celecoxib and rofecoxib were well tolerated in all cases. Twenty-three patients
      who had an anaphylactoid reaction involving dipyrone and propyphenazone showed
      good tolerance to celecoxib (which contains a pyrazole group in its structure) on
      challenge. CONCLUSIONS: The SBPCOCs with highly selective COX-2 inhibitors were
      safe in patients with single-reactive, NSAID-induced anaphylactoid reactions,
      even in cases that involved pyrazole derivatives.

PMID- 15521373
TI  - Comparative cutoff points for adenosine monophosphate and methacholine challenge
      testing.
AB  - BACKGROUND: Current use of the PC20 (provocation concentration that causes a
      decrease in forced expiratory volume in 1 second of 20%) cutoff point for
      bronchial challenge precludes its use in patients with more severe airflow
      obstruction. OBJECTIVE: To evaluate the efficacy and safety of lower cutoff
      points for adenosine monophosphate (AMP) and methacholine (MCH) bronchial
      challenge tools to monitor response to treatment in chronic asthma. METHODS: We
      retrospectively examined data from 5 previously published studies (2 using AMP, 2
      using MCH, and 1 with MCH and AMP arms) and recalculated 10% and 15% cutoff
      points for AMP and MCH. Data were analyzed for correlation of single results and
      doubling dose shifts after anti-inflammatory treatment intervention. RESULTS: A
      total of 175 individual MCH challenges and 152 AMP challenges were evaluated.
      Evaluating the doubling dose shift produced by the addition of anti-inflammatory
      treatment (inhaled corticosteroids or montelukast) produced the following Pearson
      correlation coefficients: MCH PD20 (provocation dose that causes a decrease in
      forced expiratory volume in 1 second of 20%) vs PD15, 0.80; MCH PD20 vs PD10,
      0.65; AMP PC20 vs PC15, 0.96; and AMP PC20 vs PC10, 0.84 (P < .001 for all).
      Subgroup analysis of AMP for before and after inhaled corticosteroids only (n =
      41) shows AMP PC20 vs PC15 of 0.92 and AMP PC20 vs PC10 of 0.84 (P < .001 for
      both). CONCLUSIONS: The 10% and 15% cutoff points strongly predict the 20% cutoff
      value for AMP and MCH, as do the doubling dose shifts after anti-inflammatory
      treatment. The lower thresholds are suitable for monitoring response to therapy,
      and they expose patients to significantly less provocation agent.

PMID- 15521374
TI  - Observational study of the effects of using montelukast vs fluticasone in
      patients matched at baseline.
AB  - BACKGROUND: The relative effectiveness of inhaled corticosteroids and leukotriene
      receptor antagonists in asthma therapy continues to be the subject of clinical
      studies. Recent studies have examined the impact of these therapies using a
      retrospective design. Retrospective studies require special attention to
      nonrandom assignment of participants to treatment groups and, consequently, to
      the need to appropriately account for baseline differences. OBJECTIVE: To examine
      the relative effectiveness of montelukast sodium vs fluticasone propionate as
      controller monotherapy in patients with asthma. METHODS: A retrospective cohort
      analysis of claims data from 6,160 individuals continuously enrolled in 1 of 20
      US managed care plans. Patients using fluticasone were matched to those treated
      with montelukast using propensity scores and age (2-55 years). Health care use
      was determined for the 12-month periods before and after the initial controller
      prescription. Outcomes included asthma-related hospitalizations and emergency
      department visits, along with use of oral corticosteroids and short-acting beta
      agonists. Logistic regression analyses were also performed. RESULTS: Overall,
      controller therapy significantly reduced the odds of postindex asthma-related
      hospitalizations (odds ratio, 0.56; 95% confidence interval, 0.38-0.79); no
      significant difference was observed with asthma-related emergency department
      visits (odds ratio, 0.89; 95% confidence interval, 0.76-1.04). Differences in the
      relative effect in the montelukast and fluticasone groups were not observed.
      Similarly, increases in the postindex rate of short-acting beta-agonist use and
      increases in oral corticosteroid use for both montelukast and fluticasone
      patients were noted. CONCLUSIONS: Similar outcomes were observed in montelukast
      and fluticasone users in this matched cohort analysis.

PMID- 15521375
TI  - The Copenhagen Prospective Study on Asthma in Childhood (COPSAC): design,
      rationale, and baseline data from a longitudinal birth cohort study.
AB  - BACKGROUND: The atopic diseases asthma, atopic dermatitis, and allergic rhinitis
      are the most common chronic diseases in children, and their prevalence has
      increased recently in industrialized nations. Little is known about the genetic
      environmental interaction factors driving such proliferation. OBJECTIVE: To
      investigate the relationships among genetic, environmental, and lifestyle factors
      in the development of atopic diseases in high-risk children with the aim of
      developing evidence-based prevention strategies. METHODS: The Copenhagen
      Prospective Study on Asthma in Childhood is a single-center, birth cohort study
      of children of asthmatic mothers. Objective assessments begin at birth, with
      scheduled visits every 6 months and when acute symptoms manifest. Clinical
      outcomes comprise preasthma, asthma, atopic dermatitis, allergic rhinitis,
      allergy, lung function, and bronchial responsiveness. Exposure assessments
      comprise respiratory, intestinal, and skin microbiology; the child's diet; indoor
      and outdoor air quality; allergens; and indicators of lifestyle. Genetic
      characteristics of probands and parents are evaluated. Quality assurance follows
      Good Clinical Practice guidelines. RESULTS: Four hundred eleven infants of
      asthmatic mothers were enrolled at the age of 1 month. The children were born
      between August 2, 1998, and December 28, 2001. Compared with the Copenhagen
      population, mothers of the cohort population were less likely to have given
      natural childbirth. The households were slightly less affluent, with fewer
      children and fewer pets. Whites may be overrepresented. At age 2 years, 93% of
      the infants were still actively participating in the cohort. CONCLUSIONS: This
      longitudinal birth cohort study of high-risk Danish infants consists of objective
      phenotyping, detailed information on exposure, high data quality, and a high
      participant retention rate.

PMID- 15521376
TI  - Regulatory mechanisms of Th2 cytokine-induced eotaxin-3 production in bronchial
      epithelial cells: possible role of interleukin 4 receptor and nuclear factor
      kappaB.
AB  - BACKGROUND: Several cytokine combinations have been shown to induce eotaxins in
      bronchial epithelium. The mechanism for differential regulation of eotaxin
      expression remains unclear. OBJECTIVE: To investigate the regulatory mechanisms
      of eotaxin-3 production vs eotaxin-1 production in cultured bronchial epithelium.
      METHODS: Messenger RNA (mRNA) expression levels of eotaxin-1, eotaxin-2, and
      eotaxin-3 in a human bronchial epithelial cell line (BEAS-2B) and a normal human
      bronchial epithelial cell were examined using reverse transcriptase-polymerase
      chain reaction. Protein production was determined by enzyme-linked immunosorbent
      assay. Receptor expression was examined by flow cytometry. Phosphorylation of
      signal transducer and activator of transcription factor 6 (STAT6) was examined by
      immunoblotting. RESULTS: Eotaxin-1 and eotaxin-3, but not eotaxin-2, mRNA
      expressions were induced by stimulation with interleukin (IL) 13 or IL-4.
      However, eotaxin-3 was the only protein detected after stimulation. A consistent
      10-fold difference in the potency of IL-13- and IL-4-mediated induction of
      eotaxin-3 mRNA expression was observed. Interleukin 4 induced more potent
      induction of STAT6 phosphorylation compared with IL-13. The BEAS-2B cells were
      observed to express types 1 and 2 IL-4 receptors. Pretreatment with tumor
      necrosis factor a enhanced IL-4-induced eotaxin-1, but not eotaxin-3, mRNA
      expression. An inhibitor of nuclear factor-KB inhibited IL-13- and IL-4-induced
      eotaxin-1 gene expressions. However, it enhanced eotaxin-3 gene expression.
      CONCLUSIONS: These results suggest that differences in the potency of IL-13- and
      IL-4-mediated induction of eotaxin-3 might be explained by expression of types 1
      and 2 IL-4 receptors in bronchial epithelium. Differences in eotaxin-1 and
      eotaxin-3 mRNA and protein expression might be due to differential effects of
      nuclear factor-kappaB on gene expression.

PMID- 15521377
TI  - Neonatal microscopic polyangiitis secondary to transfer of maternal
      myeloperoxidase-antineutrophil cytoplasmic antibody resulting in neonatal
      pulmonary hemorrhage and renal involvement.
AB  - BACKGROUND: Microscopic polyangiitis is a systemic vasculitis characterized by
      small vessel involvement. Studies suggest myeloperoxidase-antineutrophil
      cytoplasmic antibody (MPO-ANCA) is involved in its pathogenesis, and the titer
      may reflect disease activity. OBJECTIVE: To report a case of transplacental
      transfer of MPO-ANCA from a mother to a 33-week gestational age neonate that
      resulted in neonatal pulmonary hemorrhage and renal involvement that was
      successfully treated with high-dose steroid therapy and exchange transfusion.
      METHODS: MPO-ANCA titers from the cord blood and the neonate on the 8th, 15th,
      and 25th days of life (DOLs) were obtained. Metabolic panels and chest x-ray
      examinations were performed for the neonate and mother and the following values
      were measured: ANCA, erythrocyte sedimentation rate, C-reactive protein,
      antinuclear antibody, serial urinalysis, and complete blood cell count. Anti
      glomerular basement membrane, quantitative immunoglobulins, anticardiolipin
      antibody, and rheumatoid factor were also measured for the neonate. RESULTS: The
      neonate had elevated MPO-ANCA titers at birth. Pulmonary hemorrhage and renal
      involvement were seen on DOL 2. High-dose steroid therapy decreased symptoms
      within 1.5 hours of initiation. Exchange transfusion performed on DOL 5 removed
      all of the remaining MPO-ANCA by DOL 25. The child remains asymptomatic to date.
      CONCLUSIONS: To our knowledge, this is the first reported case of transplacental
      transfer of MPO-ANCA resulting in pulmonary-renal syndrome that was successfully
      treated with high-dose steroid therapy and exchange transfusion.

PMID- 15521378
TI  - Nonoccupationally induced allergy to monkey.
AB  - BACKGROUND: A previous study described 2 patients with occupationally induced
      asthma caused by exposure to monkey. We describe a patient who developed asthma,
      rhinitis, and conjunctivitis owing to sensitivity to a pet monkey. The patient
      had a long history of upper and lower allergic airway disease. When 2 pet macaque
      monkeys were introduced into the home, the patient noticed increasing coughing,
      wheezing, and shortness of breath. During a particularly long exposure to the
      monkey in a car, the patient developed severe wheezing, rhinitis, and
      conjunctival edema. OBJECTIVE: To demonstrate that a nonoccupational exposure to
      monkey can lead to allergic sensitivity. METHODS: Commercially obtained macaque
      monkey hair was defatted in acetone and extracted. A total of 5 microg/mL of
      extract protein was adsorbed onto microtiter plates, and an alkaline phosphatase
      enzyme-linked immunosorbent assay was performed on serum samples from 4
      individuals: 2 controls, 1 individual with suspected sensitivity, and the
      patient. A positive result was an optical density greater than twice that of the
      control. RESULTS: The patient's serum had an optical density greater than twice
      that of the control. The antibody levels of 2 control subjects-the patient's wife
      and one of the investigators-were elevated but not positive. The investigator had
      manifested asthma after exposure. CONCLUSIONS: This is the first report of
      sensitivity to monkey occurring in a nonoccupational setting.

PMID- 15521379
TI  - [Hepatic regeneration and liver failure after hepatectomy and living-donor liver
      transplantation--basic and clinical review].

PMID- 15521380
TI  - [Liver regeneration after resection: molecular and cellular mechanism].
AB  - It has been well established that the liver can regenerate after resection. Liver
      regeneration is a fundamental mechanism by which the liver responds to injury.
      This review article discusses molecular and cellular mechanism of liver
      regeneration, including growth factors and cytokines in the initiation and
      regulation of liver regeneration, the importance of the liver extracellular
      matrix and its dynamic effect on hepatocyte growth, and finally, stem cell
      biology in liver regeneration.

PMID- 15521381
TI  - [Liver regeneration after hepatectomy].
AB  - It is well known that the normal liver has enormous regenerative capacity.
      Despite years of effort by numerous investigators, there is still uncertainty
      about the signals of liver regeneration. Computed tomography (CT) is the most
      useful tool because it accurately measures human liver volume. Comparing the
      differences in regeneration after major resection of normal and injured livers,
      normal livers reached plateau levels within 1 to 2 months regardless of the
      extent of resection, whereas regeneration was retarded in injured liver. Human
      liver regeneration is influenced by the extent of resection. In biliary cancer,
      liver regeneration terminates when the liver has regained about three-quarters of
      its original size in about 1 year. The clinical significance of the observation
      that liver regeneration is an incomplete process is unclear. However, the strong
      correlation observed between body surface area and regenerated liver volume
      suggests that liver regeneration is a process of restoration of the liver to a
      volume suitable for body size. In living related-donor liver transplantation
      there is a tendency for the size of the transplanted liver to converge to the
      standard liver volume, regardless of whether the initial liver-graft volume was
      smaller or larger than the standard liver volume.

PMID- 15521382
TI  - [Mechanism of liver failure after hepatectomy].
AB  - Liver failure after hepatectomy is caused by many factors such as excessive
      hepatectomy, ischemic-reperfusion injury, postoperative infection, etc. However,
      apoptosis of hepatocytes is the most important event in the molecular mechanism
      of liver failure. Liver failure after excessive hepatectomy is characterized by
      increased apoptosis of hepatocytes and diminished liver regeneration. The former
      is induced by hypercytokinemia and hyperendotoxemia, and the latter is caused by
      cell cycle arrest. In ischemic-reperfusion injury of the liver, the apoptosis of
      hepatocytes is caused by activation of the MMPT and calpain system that are
      induced by the intracellular accumulation of Ca. The possible mechanism of liver
      failure in cases with persistent infection is the inhibition of liver
      regeneration and the induction of apoptosis of hepatocytes due to transforming
      growth factor-beta 1. The knowledge of these mechanisms will lead to prompt and
      appropriate treatments for individual patients.

PMID- 15521383
TI  - [Hepatic failure following resection of cholestatic liver].
AB  - Hepatectomy for biliary cancer with obstructive jaundice is often followed by
      postoperative septic complications associated with hyperbilirubinemia, both of
      which could lead to cholestatic liver failure by affecting each other. Such
      septic complications seem to develop from contamination of bile, reduction of
      intestinal integrity, or impairment of host resistance to bacteria, each
      resulting from biliary obstruction. Hyperbilirubinemia after hepatectomy is
      demonstrated to develop due to hepatic mitochondrial dysfunction or impaired
      expression of bile efflux pumps on the canalicular membrane of hepatocytes. Since
      no therapeutic strategy is established for liver failure following hepatectomy,
      it is important to take all possible measures before surgery to enhance the
      functions of the liver, intestine, and host immunity and to prevent postoperative
      septic complications.

PMID- 15521384
TI  - [Hepatic failure after liver resection in patients with cirrhosis].
AB  - Despite improvements in the preoperative assessment of liver function and
      advances in surgical techniques, liver resection for hepatocellular carcinoma
      still holds a risk for postoperative hepatic failure, especially in patients with
      cirrhosis. Physiologic characteristics in patients with cirrhosis include
      hyperdynamic state of the systemic circulation, decrease in hepatic blood flow,
      portal hypertension, metabolic disorders, dysfunction of the reticuloendothelial
      system, and thrombocytopenia. Surgical stress including massive bleeding,
      disturbance of hepatic circulation, and infection are risk factors for
      postoperative hepatic failure. The risk of hepatic failure also correlates with
      the severity of active hepatitis and the degree of hepatic fibrosis. To prevent
      postoperative hepatic failure, dopamine, prostaglandin, and hydrocortisone have
      been used. Although various treatments including plasma exchange have been tried
      in hepatic failure, the results have often been unsatisfactory. Careful
      preoperative evaluation of the hepatic functional reserve and the severity of
      active hepatitis, and adequate selection of surgical method are important to
      prevent postoperative hepatic failure.

PMID- 15521385
TI  - [Liver regeneration in living-donor liver transplantation].
AB  - Liver regeneration in living-donor liver transplantation is summarized from the
      authors' data. In donors, liver function tests recovered to within the normal
      range 2 weeks after surgery regardless of graft type. At 2 weeks, the volumetric
      recovery of the remnant liver was 65% and 80% of the original volume in right and
      left lobe donors, respectively. These results suggest that functional recovery
      occurs earlier than morphologic restoration in donors. In recipients, the factor
      that affected the regeneration rate in size 4 weeks after transplantation was
      only implanted graft size; the rate was greater in patients in whom smaller
      grafts were implanted. In recipients with a rate of two or more, however, high
      portal vein pressure and flow were observed. Further, persistent low platelet
      counts and hyperbilirubinemia were seen in those patients. These results indicate
      that size enlargement may be caused by engorgement, and functional recovery is
      not achieved concurrently with morphologic restoration, especially in patients
      with smaller grafts. In patients with fulminant hepatic failure who receive
      auxiliary partial orthotopic liver transplantation, sequential histopathologic
      observations of the diseased liver revealed that liver regeneration initiates
      from cytokeratin 17-positive ductules and at least 1 year is necessary for
      complete recovery.

PMID- 15521386
TI  - [Pathophysiology and strategy for small-for-size graft syndrome after living
      donor liver transplantation].
AB  - Small-for-size (SFS) graft syndrome is an important problem after living-donor
      liver transplantation in adults. Hemodynamic change is thought to be the main
      cause of graft injury. Excessive portal flow is associated with hepatic
      sinusoidal injury, and reduction of portal flow improves postoperative liver
      function. Increased venous outflow due to hepatic venoplasty or reconstruction of
      the middle hepatic vein decrease the risk of graft congestion. However, the
      intragraft acute-phase response remains unclear. Recent studies have revealed
      that downregulation of heat shock protein (HSP) may account for SFS graft injury,
      and induction of HSP may prevent SFS syndrome. On the other hand, derangement in
      the regulation of liver regeneration is recognized as another important factor.
      Further investigation of the regulatory mechanisms of liver regeneration in SFS
      grafts may suggest a strategy for the prevention and treatment of SFS syndrome.
      Successful transplantation of marginal-size liver grafts would improve outcome
      for recipients and increase the margin of safety for living donors.

PMID- 15521387
TI  - [Robot-assisted general surgery].

PMID- 15521388
TI  - [What we can learn from a case of medical malpractice].

PMID- 15521389
TI  - Back to the bedside.

PMID- 15521390
TI  - Medicinal erosion: a case report.
AB  - Patients, healthcare professionals, and health product manufacturers focus on the
      benefits that the use of a medicine or health product will bring rather than the
      potential side effects. A case of erosive tooth surface loss caused by the
      repeated and prolonged use of an acidic mouthrinse is reported. The adverse
      effects of health care products on the dentition and methods to minimise
      potential damage are discussed.

PMID- 15521391
TI  - Effect of ultrasonic vibration on the retention of adhesively luted intra
      radicular posts.
AB  - The aim of this study was to determine the effect of prolonged ultrasonic
      vibration on tensile force necessary to dislodge two different post types luted
      with an adhesive resin. Extracted human canine teeth were decoronated and root
      filled. Either a ceramic or stainless steel intra-radicular post was luted into
      each root with resin-based cement. Half the samples in each group were randomly
      assigned to be subjected to ultrasonic vibration of the post (test group), the
      remaining samples did not receive vibration (control group). The tensile force
      required to dislodge each post was then determined in a universal testing
      machine. The mean force required to dislodge the stainless steel posts in the
      control group was 510.1N (SD 170.6) and in the 'treatment' group it was 539.5N
      (SD 163.3). For the ceramic posts in the control group the mean force was 447.8N
      (SD 165.5) and in the 'treatment' group it was 473.9N (SD 137.8). There was no
      statistical difference between the groups (p = 0.597). Within the limitations of
      this in-vitro study, the results cast doubt on the ability of application of
      ultrasonic vibration to displace/loosen intra-radicular posts luted with a resin
      based cement.

PMID- 15521392
TI  - A subjective study of dimensional stability of permanent acrylic resin complete
      denture bases after a second curing cycle.
AB  - The aim of this study was to subjectively assess permanent denture base retention
      and stability in order to determine whether detrimental change occurred as a
      result of a second curing cycle. 100 complete upper denture bases were assessed
      by clinician and patient using visual analogue scales at try-in and insert. No
      statistically significant alteration in mean scores for retention and stability
      was seen. 5% of bases showed some deterioration, but none required rebasing or
      remaking as a result. The advantages of permanent bases during denture
      construction seem to outweigh the risk of loss of retention and/or stability as a
      result of distortion due to the second curing cycle.

PMID- 15521393
TI  - A cross-sectional survey of clinicians performing periodontal surgical crown
      lengthening.
AB  - The aim of this study was to conduct a survey of surgical crown lengthening
      practice performed by dental specialists and general dental practitioners using a
      cross-sectional questionnaire. One hundred general dental practitioners and 100
      specialists from each of the following specialties: prosthodontics, periodontics,
      restorative dentistry and surgical dentistry. There were fewer surgical dentists
      performing surgical crown lengthening than the other specialists. The specialists
      in periodontics were significantly more likely to perform surgical crown
      lengthening than not. The respondents predominantly considered that periodontal
      surgical crown lengthening is within the remit of periodontics. 33% of the
      respondents performing more than 50 PSCL procedures in one year thought that the
      gingival margin was stable after three months. 33% thought that it was stable
      after six months and 33% declined to state a post-operative marginal stability
      time period.

PMID- 15521394
TI  - Microbiological hazard analysis in dental technology laboratories.
AB  - Dental technicians are trained in a range of skills involved in the fabrication
      of prostheses used in the mouth and facial region. Items entering the dental
      laboratory are essentially inert materials which have been in contact with the
      patient's mouth, saliva, and possibly blood. Appliances leaving the laboratory
      are then returned to the clinician to be tried/inserted in the patient's mouth.
      Relatively little attention has been paid to infection control policy within
      dental laboratories, perhaps due to perceived and/or actual remoteness from
      patients, lack of appropriate training, and lack of relevant research. More
      controlled studies are desirable, in order to identify any potentially hazardous
      procedures, and to make an assessment of risk for these procedures.

PMID- 15521395
TI  - Wettability of some packable resin-based composites. An in vitro study.
AB  - The purpose of this research was to measure the contact angles of some packable
      resin-based composites in order to determine their wettability related to the
      surface energy. Materials were manipulated according to the manufacturer's
      instructions and were inserted in a circular metallic matrix and photo cured for
      40 seconds on both sides. The specimens were removed and finished with silicon
      carbide metallurgical finishing paper (800 gifts). Half of each specimen was
      covered by a layer of Bis-GMA and photo cured for 20 seconds. The specimens were
      then submitted to measurements in a contact angle goniometer with two different
      liquids and polarities in three points. The materials without Bis-GMA covering
      layer showed statistically significant differences related to contact angles and
      among the materials and liquids (p<0/05).

PMID- 15521396
TI  - Reliability of a measuring-procedure to locate a muscle-determined centric
      relation position.
AB  - Although reproducibility of centric relation position, determined with an
      anterior deprogramming device, a leaf gauge, is widely accepted among clinicians,
      data confirming statistical evidence are lacking in the current literature. The
      objective of this study was to prove clinical reliability of a measuring
      procedure to locate the centric relation position, determined with the leaf
      gauge. A sample of 15 subjects (6 men, 9 women, age 22 to 46), assessed with the
      Research Diagnostic Criteria to rule out any TMD-signs, was selected. Three
      observers each took three sequential interocclusal records with the leaf gauge,
      to mount a set of casts into the centric relation position in an articulator. Out
      of 15 subjects, 12 (5 men, 7 women) fitted criteria of precision--three out of
      three interocclusal records for each of the three observers--in a split-cast
      procedure. The applied statistical method is an analysis of variance model
      (ANOVA) with two factors for 3 observers and 12 subjects. The variance components
      estimation procedure is MIVQUE (0). The a was set at 0.05. No significant
      difference between observers for the measured variables sagittally (XL, XR),
      transversally (YL, YR), and vertically (ZL, ZR) could be found. MIVQUE variance
      components estimates for observers is < 0, varies for subjects from 0.04 to 0.20
      and varies for error from 0.12 to 0.25 mm. Reliability of a measuring-procedure
      to locate a muscle-determined centric relation position could be established
      satisfactory.

PMID- 15521397
TI  - Systematic review of the evidence supporting intra-oral maxillofacial
      prosthodontic care.
AB  - The literature on maxillofacial prosthodontics may be considered to be dominated
      by articles describing case reports or case series. Prospective, well-controlled
      clinical trials are scarce owing to the inherent difficulty of performing such
      trials in patients suffering from oral cancer. The aim of this study was to
      perform a systematic review of the literature relating to intra-oral
      maxillofacial prosthodontics based on the principles of evidence-based dentistry.
      A detailed report of the findings is presented and critically assessed and a
      discussion of the outcome in respect to the various confounding factors is
      carried out. Finally, suggestions for future research in the field of
      maxillofacial prosthodontics are made.

PMID- 15521398
TI  - [Value of autologous chondrocyte transplantation in experimental cartilage
      defects reconstruction. Part IV--Microscopic analysis of repair tissue
      degenerative changes (cellularity and signs of necrosis)].
AB  - Articular cartilage cells are immersed in semi-solid matrix and isolated from the
      rest of the body because of lack of nervous fibres, and blood and lymphatic
      vessels. Trauma and aging processes result in cartilage ultrastructure disorders.
      Those changes leads to progressive decreasing of durability and rigidity of
      cartilage. Research on articular cartilage reconstruction focuses on, among other
      things, reaching by newly formed tissue optimal amount of vital cells. The aim of
      this part of the study was microscopic evaluation of repair tissue degenerative
      changes (cellularity and signs of necrosis). MATERIAL AND METHODS: Repair of
      partial thickness cartilage defect (III tertiary grade) on distal femur joint
      surface was evaluated (25 adolescent rabbits). Procedures were performed in two
      groups: I--autologous chondrocyte transplantation under periosteal flap, II-
      periosteal graft. Chondrocytes were isolated from the cartilage specimens by
      enzymatic digestion and cultured in vitro. The follow-up periods were established
      at 4, 8 and 12 weeks. Repair tissue was evaluated microscopically according to
      modified O'Driscoll scale. RESULTS: Repair tissue cellularity. In group I (with
      chondrocytes), 4 weeks after the procedure tissue of high cellularity was formed,
      corresponding in amount of cells to the structure of early differentiated hyaline
      like cartilage. Amount of cells slightly decreased with time, as it occurs in
      maturing cartilage. In group II (without chondrocytes), 4 weeks after the
      procedure the repair tissue was characterized by small amount of cells, which was
      decreasing with time. Signs of necrosis. In group I, 4, 8 and 12 weeks after the
      procedure moderate intensity of necrotic signs was observed. In group II,
      significant intensity of necrosis signs in all observation periods was observed.
      CONCLUSION: Obtained results indicate, that autologous chondrocyte
      transplantation in treatment of partial thickness cartilage defects effects with
      forming tissue of high cellularity, not degenerating with time, much better as
      compared to untreated defect.

PMID- 15521399
TI  - [Active range of cervical motion in healthy subjects and in spinal disorders. DBC
      equipment validity in complex cervical motion evaluation].
AB  - Active Range of motion (AROM) is one of the crucial parameters assessed in the
      cervical spine evaluation. Repeated standardized AROM evaluation enables
      objectified monitoring of disease progress or therapy related improvement. Active
      spine therapy according to DBC (Documentation Based Care) requirement is a
      contemporary therapeutic system with proven efficacy in spinal disorders. The
      therapeutic concept f DBC is mechanotherapy based and introduces special devices
      designed for active exercises in strictly defined range, rate and load. DBC-3CR
      device is constructed for active motion (composed of rotation, anteflexion and
      lateral flexion) exercise of the cervical spine with repeated dynamic load.
      Technical properties allow to avail the machine for diagnostic purposes as far
      complex range of motion is concerned. PURPOSE: Comparison of AROM between healthy
      volunteers and patients with cervical disorders. Evaluation of DBC-3CR validity
      in complex AROM measurement Patients: A--99 healthy volunteers; B--106 patients
      with chronic neck pain resulting from cervical spondylosis; C--36 patients with
      acute neck pain related to cervical disc disease or whiplash injury. METHODS:
      Complex AROM detection with DBC-3CR was compared with reference measurements
      (goniometric and inclinometric simple AROM detection). Age and sex dependence of
      AROM among healthy subjects was observed. AROM was compared between B, C and
      reference groups. DISCUSSION: AROM was significantly decreased in patients with
      chronic and acute neck pain. Motion limitation pattern was symmetric in both
      groups. The presence of linear dependency between complex AROM acquired with DBC
      3CE and rotation acquired with goniometer was observed (Pearson coefficient 0.81
      at p < 0.0001). CONCLUSIONS: I. DBC-3CR device is useful in AROM evaluation. 2.
      AROM in healthy subjects decreases with age, but is sex--independent parameter.
      3. In cervical spondylosis AROM is symmetrically reduced as far as rotation and
      lateral flexion are concerned. 4. Acute cervical pain results in symmetric AROM
      limitation.

PMID- 15521400
TI  - [Lumbar spinal stenosis operative treatment--early results].
AB  - Early results (12 weeks after surgery) of the lumbar spinal stenosis operative
      treatment were assessed in the group of 36 patients (aged 40-65 years). In 72% of
      patients posterior fusion was applied. In the results evaluation lumbar pain, low
      extremities pain, neurogenic claudicat ion, sensory disturbances and functional
      status were taken in account. A significant decrease in low extremities and
      lumbar pain was observed. Some sensory disturbances after operative treatment did
      not affect general high patients assessment of the performed surgical procedures
      (positive 80.5% cases).

PMID- 15521401
TI  - [The long-term results of decompression and anterior lumbar interbody fusion for
      the treatment of degenerative lumbar spondylolisthesis].
AB  - In this paper we reviewed 31 patients who had been treated surgically for lumbar
      degenerative spondylolisthesis. They were operated between 1990-1996. The
      decompression and anterior lumbar interbody fusion with use of autologous bone
      graft,was performed in all of them. The duration of follow-up ranged from 12 to 6
      years. The outcome was assessed using rating system of Prolo and VAPS. The disc
      high, degree of slippage, segmental lordosis, before surgery, after 6 weeks and
      at the time of final follow-up were measured on the radiographs. In all cases
      spinal fusion were achieved. A significant decrease in radicular pain and low
      back pain was seen but the relation between clinical and radiological outcomes
      was not observed.

PMID- 15521402
TI  - [Revision hip arthroplasty after prosthesis removal in septic loosening].
AB  - The author presents the therapeutic protocol in "hanging hip" after prosthesis
      removal in septic loosening, basing on a series of 11 patients--7 females and 4
      males--age ranging from 31 to 67 years. On average the primary prosthesis was
      removed 2.5 years after implantation, while patients remained with a "hanging
      hip" for an average period of 2.2 years (limb shortening before revision
      arthroplasty was on average 4.5cm). When qualifying patients for revision
      arthroplasty the following parameters were taken into account: sedimentation
      rate, CRP reactive protein levels, bacteriological blood culture results,
      cultures from the hip punctate, every-day life activity and post-op patient
      compliance with the therapy. Acetabular roof defects were managed according to
      Zuk's method. Clinical assessment of the patients was performed 6 weeks, 3, 6 and
      12 months using Merle-d'Aubigne and Postel classification, while X-rays were used
      to assess proper prosthesis implantation. During follow-up proper prosthesis
      implantation was found in all cases, while no signs of re-infection, nor
      radiological and clinical signs of implant loosening were noted. Clinical
      assessment of the patients yielded 1 very good result, 7 good results and 3
      satisfactory. The presented material indicates that good results can be obtained
      in prosthesis reimplantation after removal of the primary prosthesis because of
      its septic loosening.

PMID- 15521403
TI  - [Neurological complication after total hip replacement].
AB  - The study was performed to evaluate neurological complication of 562 patients who
      had undergone primary total hip replacement. Lesions of sciatic, femoral and
      common peroneal nerve occurred in 18 patients (3.2%). Paresis of peroneal nerve
      was demonstrated in 15 patients. Within this group 7 patients had elongation of
      the extremity above 4 cm, and 8 patient had it in the range of 2-3 cm. Paresis of
      common peroneal nerve took place after direct compression of region of fibular
      head. Lesion of femoral nerve happened twice. In the group of 14 patients
      clinical symptoms of nerve paresis healed spontaneously in 6-12 month time. In
      the group of 4 patients (0.7%) constant lost of dorsal flexion of the foot was
      observed.

PMID- 15521404
TI  - [Premature femoral head growth plate closure in Perthes' disease].
AB  - The study population consisted of 311 patients (50 female and 261 male) who had
      reached skeletal maturity at last follow up (361 hips). The mean age at the onset
      of symptoms was 6 years and 10 months (range: 2.5-13 years). All patients were
      treated by containment methods (bed rest and traction in abduction, brace, Petri
      cast, varus osteotomy, Salter osteotomy and shelf operation). Premature growth
      plate closure was estimated according to Bowen (central and lateral). Necrosis of
      the femoral head was classified according to Herring and Catterall, late results
      according to Stulberg and Mose and leg length discrepancy on scanograms. Article
      trochanter distance (ATD) was estimated according to the Edgren methods.
      Premature femoral head growth plate closure was found in 61 hips (central--41 and
      lateral--20). Statistical analysis did not reveal any correlation between the
      gender and type of treatment and premature growth plate closure. The central
      pattern of growth plate closure was more often seen to 6 years of age at the
      onset and the lateral over 9 years of age at the onset (p = 0.0176). Premature
      growth plate closure was observed more often in Herring group C and Catterall
      group 4 (p = 0.0001). Disturbances in femoral head sphericity according to Mose
      increased (except with bilateral Perthes' disease) and ATD decreased in patients
      with premature growth plate closure. Also premature growth plate closure
      increased the leg length discrepancy in Perthes' disease. Thirty two (52.5%) hips
      with abnormal physeal growth were classified into type I or II according to
      Stulberg classification, 16 (26.2%) into type III and 13 (21.3%) into type IV or
      V. Premature growth plate closure in Perthes' disease is more common in huge
      necrosis of the femoral head. The central pattern of growth plate closure is more
      often in younger children (to 6 years of age) and the lateral in older (over 9
      years of age). With abnormal physeal growth the greater trochanter overgrow and
      ATD decreased, the leg length discrepancy and disturbances in sphericity of the
      femoral head increased. Premature growth plate closure increased satisfactory and
      poor results according to Stulberg classification.

PMID- 15521405
TI  - [Local or regional anesthesia in knee arthroscopic surgery--patients
      satisfaction].
AB  - There is no doubt, that local anesthesia for knee arthroscopic surgery is rather
      simple, reliable, well tolerated, cost-effective and safe procedure acceptable
      also for one-day-surgery and outpatients. Patient's acceptance and satisfaction
      are behind those measurable data and could be predicted only after the question
      if the patients would prefer intraarticular analgesia when they should need to
      have another arthroscopy performed. The aim of the investigation was to compare
      this prediction with real patients feeling. Comparison was made between the types
      of anesthesia (regional, intraarticular) used for knee surgery, twice the same
      knee and patient. The retrospective data (mean 9 months after the last surgery)
      showed higher patients satisfaction (93.5%) with local anesthesia if compare with
      regional (2.6%) and femoral nerve block (3.9%).

PMID- 15521406
TI  - [Hand injuries in the Krakow Region].
AB  - The material of 1199 patients with hand injuries treated in the II Department of
      Surgery in Krakow within the years 1987-2000 was epidemiologically elaborated.
      The adult population in this region counts 850,228 thousand inhabitants,
      therefore the number of hand injuries demanding special procedures amounts 5.74
      for 10 thousand inhabitants yearly. Hand injuries most frequently affected young
      manual workers before 40 years of age (p < 0.001). Almost one half of accidents
      occurred at home (45.29%), and only 19.68% were work-related (p < 0.001).
      Machinery accidents (34.87%) and cutting with glass (18.43%) were two the most
      common causes of these injuries (p < 0.001). After the operation, prevalent
      number of patients (72.56%) were treated as an outpatient. The mean period of
      whole treatment amounts 76.95 +/- 67.81 days. It has been depended on the
      severity of injury and complications as well (p < 0.001). 90.59% of patients
      returned to previous work, and 4.89% of patients had to change their work.
      Disability pension was given to 4.50% of all patients.

PMID- 15521407
TI  - [Anatomical basis for a surgical treatment of cubital tunnel syndrome].
AB  - The paper presents anatomical basis for a surgical treatment of cubital tunnel
      syndrome. There are five major anatomical locations where the ulnar nerve may be
      compressed near the elbow. Transfer of the ulnar nerve decompresses all five
      locations simultaneously and thus theoretically may be more reliable.

PMID- 15521408
TI  - Falling through the net. Interview by Dina Leifer.

PMID- 15521409
TI  - How low can you go?

PMID- 15521410
TI  - A world turned upside down. Interview by Christian Duffin.

PMID- 15521411
TI  - Tribute to a visionary. Interview by Lynne Pearce.

PMID- 15521412
TI  - Has it all been worth it?

PMID- 15521413
TI  - Pay and conditions.

PMID- 15521414
TI  - Understanding social stigma in women with hepatitis C.
AB  - AIM: The aim of this research is to gain a more complete understanding of the
      impact of the hepatitis C virus (HCV) on women. METHOD: This research used
      qualitative methods. Semi-structured interviews were carried out with eight HCV
      positive women. The interviews explored counselling and testing, social stigma,
      treatment options, transmission and gender roles, and the influence of
      reductionism on the experience of HCV-positive women attending services.
      FINDINGS: All the women experienced significant difficulties coming to terms with
      the diagnosis. Many had worries about transmission and stigma--these worries
      affected their relationships, including those with sexual partners, family
      members and children. Most of the women had mixed feelings about knowing their
      diagnosis and varying levels of satisfaction with treatments and services
      provided. CONCLUSION: Women appear to have individual anxieties related to the
      transmission of HCV and their ability to carry out their social roles. They were
      particularly concerned about social stigma, sexual transmission, pregnancy and
      childcare. These worries affected their close relationships and resulted in
      concerns about their ability to fulfil expected gender roles.

PMID- 15521415
TI  - Respiratory care in community settings.
AB  - BACKGROUND: This article reviews the nurse's role in respiratory care in
      community settings. It aims to identify successful models of community-based
      respiratory care so that future models and programmes can benefit. CONCLUSION:
      From the literature it is evident that the nurse's role could be strengthened by
      the national standardisation of education and the development of models of care
      and relevant career paths. Improvements to patient care could include the
      addition of palliative counselling services, general psychosocial support care,
      auditing patient satisfaction and implementing individualised care plans.

PMID- 15521416
TI  - Tuberculosis and HIV infection: minimising transmission.
AB  - Tuberculosis and human immunodeficiency virus have developed as co-infections
      globally and are now affecting the UK. Nurses should be aware of the need to have
      effective infection control policies to manage this serious condition.

PMID- 15521417
TI  - Perpetual postponers? Women's, men's and couple's fertility intentions and
      subsequent fertility behaviour.
AB  - In this article data from the British Household Panel Study (BHPS) are used to
      analyse gender differences in fertility intentions, and the correspondence
      between fertility intentions and subsequent fertility behaviour. By exploiting
      couple-level data, we examine whether partners have conflicting preferences for
      future fertility. Focusing on women who remain childless in their thirties we
      look at socio-demographic factors related to the intention to remain childless,
      or to start a family later on in life. By following up women over time, the
      characteristics of women who go on to have a child later on in life are
      considered. The importance of having a partner and the fertility intention of
      that partner in predicting whether a birth will occur are also examined.

PMID- 15521418
TI  - Characteristics of sole registered births and the mothers who register them.
AB  - This article explores the characteristics of live births where no father was
      present on the birth certificate (sole registrations) using registration data. It
      then uses data from the ONS Longitudinal Study to examine some characteristics of
      mothers who have ever experienced a sole registered live birth. It shows that as
      a proportion of all births, sole registrations have remained fairly constant over
      the last two decades, although since 1998 there is some evidence of a fall in the
      proportion. For mothers born between 1955 and 1962 around nine per cent
      experienced a sole registration. Those who ever experienced a sole registration
      were around four years younger when they began their childbearing. These women
      also had larger families and were more likely to come from a lower social class
      background.

PMID- 15521419
TI  - Estimates of true birth order for Scotland, 1945-1999.
AB  - Over the last three decades fertility in Scotland, as measured by the total
      fertility rate (TFR), has moved from being higher than in England and Wales, to
      being lower. The annual number of births in Scotland has declined so that in the
      mid-1990s low fertility became the main driver of the overall population decline
      that Scotland has been experiencing since 1974. Analysis of fertility by birth
      order is instrumental in gaining an understanding of past and future fertility
      trends. Until the rise in births outside marriage in the 1980s data from
      registration could be used as a proxy for true birth order. However, because
      birth order is not collected for births outside marriage true birth order now has
      to be estimated. This article presents the first official estimates of true birth
      order for Scotland. The construction of these estimates based on a modified
      version of the method used for England and Wales is discussed. This article also
      presents analysis relating births by true birth order estimate to the population
      of women by parity on a cohort basis, and makes comparisons with England and
      Wales.

PMID- 15521420
TI  - Number and nuclear localisation of nucleoli in mammalian spermatocytes.
AB  - In seven mammalian species, including man, the position and number of nucleoli in
      pachytene spermatocyte nuclei were studied from electron microscope (EM) nuclear
      sections or bivalent microspreads. The number and position of the nucleolar
      organiser regions (NORs) in mitotic and meiotic chromosomes were also analysed,
      using silver staining techniques and in situ hybridisation protocols. The general
      organisation of pachytene spermatocyte nucleoli was almost the same, with only
      minor morphological differences between species. The terminal NORs of Thylamys
      elegans (Didelphoidea, Marsupialia), Dromiciops gliroides (Microbiotheridae,
      Marsupialia), Phyllotys osgoodi (Rodentia, Muridae) and man, always gave rise to
      peripheral nucleoli in the spermatocyte nucleus. In turn, the intercalated NORs
      from Octodon degus, Ctenomys opimus (Rodentia, Octodontidae) and Chinchilla
      lanigera (Rodentia, Cavidae), gave rise to central nucleoli. In species with a
      single nucleolar bivalent, just one nucleolus is formed, while in those with
      multiple nucleolar bivalents a variable number of nucleoli are formed by
      association of different nucleolar bivalents or NORs that occupy the same nuclear
      peripheral space (Phyllotis and man). It can be concluded that the position of
      each nucleolus within the spermatocyte nucleus is mainly dependent upon: (1) the
      position of the NOR in the nucleolar bivalent synaptonemal complex (SC), (2) the
      nuclear pathway of the nucleolar bivalent SC, being both telomeric ends attached
      to the nuclear envelope, and (3) the association between nucleolar bivalents by
      means of their NOR-nucleolar domains that occupy the same nuclear space. Thus,
      the distribution of nucleoli within the nuclear space of spermatocytes is non
      random and it is consistent with the existence of a species-specific meiotic
      nuclear architecture.

PMID- 15521421
TI  - Phylogeny of triatomine vectors of Trypanosoma cruzi suggested by mitochondrial
      DNA sequences.
AB  - The subfamily Triatominae (Hemiptera: Reduviidae) comprises hematophagous
      insects, most of which are actual or potential vectors of Trypanosoma cruzi, the
      protozoan agent of Chagas' disease (American trypanosomiasis). DNA sequence
      comparisons of mitochondrial DNA (mtDNA) genes were used to infer phylogenetic
      relationships among 32 species of the subfamily Triatominae, 26 belonging to the
      genus Triatoma and six species of different genera. We analyzed mtDNA fragments
      of the 12S and 16S ribosomal RNA genes (totaling 848-851 bp) from each of the 32
      species, as well as of the cytochrome oxidase I (COI, 1447 bp) gene from nine.
      The phylogenetic analyses unambiguously supported several clusters within the
      genus Triatoma. In the morphological classification, T. costalimai was placed
      tentatively within the infestans complex while T. guazu was not included in any
      Triatoma complex. The placement of these species in the molecular phylogeny
      indicated that both belong to the infestans complex. We confirmed with a strong
      support the inclusion of T. circummaculata, a member of a different complex based
      on morphology, within the infestans complex. On the other hand, the present
      phylogenetics analysis did not support the monophyly of the infestans complex
      species as it was suggested in our previous studies. While no strong inference of
      polyphyly of the genus Triatoma was provided by the bootstrap analyses, the other
      species belonging to Triatomini analyzed could not be distinguished from the
      species of Triatoma.

PMID- 15521422
TI  - Characterisation and interpopulation variability of a complex HpaI satellite DNA
      of Drosophila seriema (repleta group).
AB  - A HpaI satellite DNA has been isolated and characterised from the genome of
      Drosophila seriema, a cactus-breeding species endemic to the rock fields of the
      Espinhaco Range in Brazil. The monomer sequences are slightly A + T rich (66%)
      and there is a significant variation of repetition length (343-391 bp). The
      length variability is mainly due to a 22 bp indel in some repeats and the
      presence of a highly variable region characterised by several DNA rearrangements,
      including indels, inversions and duplications of small sequence segments. The
      retarded mobility of monomers observed after gel electrophoresis suggests DNA
      curvature. Thirty satDNA repeats were analysed in samples from five populations
      which cover D. seriema geographical distribution. Previous studies showed that
      these populations present low levels of chromosomal divergence in contrast to
      high levels of mtDNA divergence. The variability among the 30 repeats is pretty
      low, on average 2%. The results showed that the satDNA sequences are rather
      homogeneous on both intra and interpopulational levels, presenting no specific
      feature(s) that could discriminate a particular population or groups of
      geographically close populations. Possible factors responsible for such
      homogeneity are discussed.

PMID- 15521423
TI  - Allozyme differentiation of four populations of Hypostomus (Teleostei:
      Loricariidae) from Ribeirao Keller, a small stream in the upper Rio Parana basin,
      Brazil.
AB  - Hypostomus hermanni (Ihering, 1905) and three other morphotypes of the genus
      Hypostomus were collected from the Ribeirao Keller, a small tributary of Rio
      Ivai, a tributary of upper Rio Parana. An allozyme analysis of 25 gene loci
      revealed diagnostic loci alleles for each population and there were fixed
      differences between some of them at some loci. Thus all populations were
      genetically distinct, although there were many common alleles. Heterozygosity
      (He) ranged from 0.059 in Hypostomus sp. 2 to 0.144 in Hypostomus sp. 1 and was
      higher than the average for other species of Hypostomus and also for fish in
      general. H. hermanni and Hypostomus sp. 1 were more similar to each other (I=
      0.878) whereas H. hermanni and Hypostomus sp. 2 showed the least genetic identity
      (I = 0.392).

PMID- 15521424
TI  - The cytological mechanism of low fertility in the naked seed rice.
AB  - The low fertility of naked seed rice (NSR) was investigated by the following
      observations: somatic chromosome constitute, behavior of pollen mother cells
      (PMCs), the germination of mature pollen grains, the development of male and
      female gametes and the structure of the anther opening. The results indicated
      that somatic chromosomal number was 2n = 24, behavior of PMCs were normal and
      most of pollen grains could regularly develop further to mature male gametophytes
      in NSR. And dehiscence chamber and thickened endothecium cell (TEC) in numerous
      anthers of the NSR were developed abnormally after dicaryotic phase, result in
      few anthers complete opening and most partly opening or failure to opening,
      therefore much fewer of pollen grains attach on the stigma as compared with
      normal variety. Furthermore most of embryo sacs possessed abnormal structure and
      were sterile. All of above illustrated that the failure of the anther opening and
      the abortion of female gametophyte were main factors controlling the low seed
      setting rate of the NSR.

PMID- 15521425
TI  - Temporal and spatial genetic variability in white-tailed deer (Odocoileus
      virginianus).
AB  - Starch-gel electrophoresis was used to assess temporal and spatial genetic
      variation in populations of white-tailed deer (Odocoileus virginianus) in western
      Tennessee. Samples of liver and kidney obtained from animals at five localities
      during 1985-1992 were analyzed at 11 loci known to be polymorphic in white-tailed
      deer. There were minimal significant differences in allelic frequencies between
      sexes and among age groups for each year at each locality and among years at each
      locality with ages and sexes combined. No significant difference occurred among
      mean values of heterozygosity. A heterozygote deficiency was detected in white
      tailed deer populations from western Tennessee and could reflect limited
      inbreeding but was more likely due to Wahlund effects. Limited temporal variation
      occurred among years within a locality and indicated a stasis in terms of minimal
      genetic drift and harvest effects on genetic structure of the populations. Herd
      origin, stocking history of populations, and gene flow were probable causes of
      spatial heterogeneity in deer populations in western Tennessee.

PMID- 15521427
TI  - Mutational load and the transition between diploidy and haploidy in experimental
      populations of the yeast Saccharomyces cerevisiae.
AB  - Mutations were accumulated over hundreds of generations in a mutator strain of
      yeast in a constant laboratory environment. This ensured that mutations were
      frequent and that the quality of environment remained unchanged. Mutations were
      accumulated in asexual populations of diploids but their impact on fitness was
      tested both for the diploid clones and for haploid clones derived from them.
      Dozens of harmful and lethal mutations accumulated in diploids, but important
      phenotypic traits, such as maximum growth rate, did not deteriorate by more than
      10%. There were no signs of decline in population size. In strong contrast, the
      populations of haploids derived from the diploids suffered from high mortality;
      their density was reduced by more than three orders of magnitude. These findings
      indicate how ineffective natural selection can be in removing deleterious
      mutations from populations of clonally reproducing diploids. They also suggest
      that phenotypic assays of heterozygous diploids may be of little value as
      indicators of increasing genetic degeneration.

PMID- 15521426
TI  - Enzyme activities and alcohol tolerance in isofemale lines of Drosophila
      melanogaster originating from different habitats.
AB  - Enzyme activity variation was studied in a Drosophila melanogaster population
      from two villages (Tiszafured and Tiszaszolos) in Hungary. Two habitats
      (distillery and farmyard) were sampled in both villages and 8-9 isofemale lines
      were established from each sample with a total of 35 lines. The activities of
      ADH, alphaGPDH, IDH and 6PGDH were determined on starch gel after electrophoresis
      in 10 F1 females of each of the 35 isofemale lines. Three sublines were
      established from three selected isofemale lines of all four samples (altogether
      36 sublines). Alcohol tolerance of the adult flies was assayed in these sublines.
      The activity of ADH was similar in the two habitats; so was the sensitivity to
      ethanol. Accordingly, no differences in adaptation to environmental ethanol were
      detected between the two habitats. The deviations between the two habitats in
      average activities and in the total variation of enzyme activities were not
      consistent in the two villages. These results suggest that founder effects and
      genetic drift are more pronounced in distilleries than selection. The association
      among enzyme activities varied greatly both between the two villages and between
      the two habitats. The two parameters of alcohol tolerance were not significantly
      different between the two habitats in any of the two villages.

PMID- 15521428
TI  - Comparative and evolutionary analysis of the cytochrome b sequences in cyprinids
      with different ploidy levels derived from crosses.
AB  - The mitochondrial cyt b genes in the allotetraploid and triploid crucian carp as
      well as triploid common carp were isolated and completely sequenced. Their DNA
      sequences were compared with those derived from the cyt b genes of the red
      crucian carp, Japanese crucian carp, and common carp with MEGA 1.0 software.
      Phylogenetic analysis revealed the sister relationships between allotetraploid
      and diploid red crucian carp, between the triploid crucian carp and diploid
      Japanese crucian carp, and between triploid common carp and diploid common carp.
      Our results indicated the cyt b genes in the allotetraploid, triploid crucian
      carp, and triploid common carp were maternally inherited. Through maternal
      inheritance, the cyt b gene in the F11 tetraploid displayed extremely high
      similarity to that in the female parent red crucian carp after 11 generations
      (from F1 to F11 hybrids). Since the establishment of the new tetraploid stocks
      has great significance in analyzing evolutionary theory of vertebrate and in
      improving aquaculture industry, analysis of the cyt b gene and the elucidation of
      the variation of the cyt b gene DNA in different cyprinids prove that cyt b is a
      useful genetic marker to monitor the variations in the progeny of the crosses.

PMID- 15521429
TI  - Molecular basis of transferrin polymorphism in goldfish (Carassius auratus).
AB  - Transferrin (TF) polymorphism was investigated in a color variety of goldfish
      (Carassius auratus), and its molecular basis analyzed. Three TF variants (A1, A2
      and B1) were identified from an inbred strain of the goldfish, of which A1 and B1
      displayed a large electrophoretic difference on both native and SDS-PAGE gels.
      The TF cDNAs corresponding to variants A1 and B1 were cloned and sequenced from
      A1A1, A1B1 and B1B1 individuals, and their deduced amino acid sequences were
      analyzed. Substantial amino acid variation occurred between variants A1 and B1,
      with significant differences in peptide length, theoretical molecular weight (Mw)
      and isoelectric point (pI). No potential glycosylation sites were observed in the
      two amino acid sequences, which excluded the possibility that carbohydrate
      difference might cause electrophoretic variation among the TF variants. Further
      analysis suggested that the distinct electrophoretic mobility of the two variants
      A1 and B1 by SDS-PAGE resulted from their Mw difference, while the difference by
      the native PAGE could be explained by their pI variation. Furthermore, genomic
      DNA fragments containing the transferrin alleles were amplified and subjected to
      RFLP analysis in A1A1, A1B1 and B1B1 individuals. The data revealed
      characteristic banding patterns for each TF genotype, and demonstrated that the
      TF alleles A1 and B1 could be used as a co-dominant marker system. The initial
      work relating to the goldfish TF variants will benefit the understanding of the
      evolutionary and functional significance of TF polymorphism in fish.

PMID- 15521430
TI  - Comparative analysis (Hippotragini versus Caprini, Bovidae) of X-chromosome's
      constitutive heterochromatin by in situ restriction endonuclease digestion: X
      chromosome constitutive heterochromatin evolution.
AB  - The Bovidae X-chromosome shows a considerable variation, in contrast to the
      preservative autosomal conservatism. The X-chromosome variation is mostly a
      consequence of the constitutive heterochromatin (CH) variation; in what respect
      to its amount and position. This is especially common among the non-Bovinae
      subfamilies and tribes. In order to characterize the X-chromosome CH in non
      Bovinae species--Hippotragini and Caprini tribes--we have used restriction
      endonuclease digestion on fixed chromosomes and sequential C-banding. With these
      techniques we were able to distinguish between the two X-chromosome types
      (Hippotragini and Caprini) CH, in what respect to its position and molecular
      nature. Moreover, we define at least, six subclasses of CH in both X-chromosome
      types analyzed. Evolutionary considerations were draw based on the results
      obtained. The technology used here for the analysis of the Bovidae X-chromosome
      CH showed to be more evolutionary informative than the classical approaches.

PMID- 15521431
TI  - Fort Dodge recalls ProHeart 6, citing FDA safety concerns. Advisory committee to
      review FDA findings.

PMID- 15521432
TI  - Veterinary research study moves forward. National academies calls on animal
      health experts for input.

PMID- 15521433
TI  - Coalition presses microchip makers for global scanner. Scanner sought that reads
      U.S. and ISO chips.

PMID- 15521434
TI  - VMAT deployment to New York involved dual role.

PMID- 15521435
TI  - Valuable information regarding generic drugs. Cutting costs by going generic.

PMID- 15521436
TI  - Veterinary response teams proliferate. Veterinarians train for disease outbreaks
      and disasters.

PMID- 15521437
TI  - What is your diagnosis? Uterine leiomyoma.

PMID- 15521438
TI  - What is your diagnosis? Increased soft tissue opacity in the right nasal passage.

PMID- 15521439
TI  - Principles of an infectious disease control program for preventing nosocomial
      gastrointestinal and respiratory tract diseases in large animal veterinary
      hospitals.

PMID- 15521440
TI  - Evaluation of a focused assessment with sonography for trauma protocol to detect
      free abdominal fluid in dogs involved in motor vehicle accidents.
AB  - OBJECTIVE: To establish a focused assessment with sonography for trauma (FAST)
      protocol in dogs, determine whether FAST can be performed by veterinary
      clinicians without extensive ultrasonographic experience, and assess the
      frequency of free fluid (as determined via FAST) in the abdominal cavity of dogs
      following motor vehicle accidents (MVAs). DESIGN: Prospective study. ANIMALS: 100
      client-owned dogs evaluated within 24 hours of an MVA. PROCEDURE: Dogs were
      placed in lateral recumbency for the FAST examination. To detect fluid in the
      abdomen, 2 ultrasonographic views (transverse and longitudinal) were obtained at
      each of 4 sites (just caudal to the xiphoid process, on the midline over the
      urinary bladder, and at the left and right flank regions). RESULTS: In the 100
      dogs evaluated via FAST, free abdominal fluid was detected in 45 dogs. In 40 of
      those 45 dogs, abdominocentesis was performed; hemoperitoneum and uroperitoneum
      were diagnosed in 38 and 2 dogs, respectively. Compared with dogs that had no
      free abdominal fluid detected via FAST, dogs that had free abdominal fluid
      detected via FAST had significantly higher heart rates and serum lactate
      concentrations and significantly lower PCVs and total solid concentrations.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that FAST is a simple and
      rapid technique that can be performed on dogs in an emergency setting to detect
      intra-abdominal free fluid and can be performed by veterinary clinicians with
      minimal previous ultrasonographic experience.

PMID- 15521441
TI  - Use of a jugular vein autograft for reconstruction of the cranial vena cava in a
      dog with invasive thymoma and cranial vena cava syndrome.
AB  - A spayed female dog was evaluated because of edema of the ventral cervical
      region, lethargy, cough, and reduced exercise tolerance. Invasive thymoma and
      cranial vena cava syndrome were diagnosed by use of ultrasound-guided fine-needle
      biopsy and contrast-enhanced helical computed tomography. Resection of the
      cranial vena cava and an autogenous jugular vein graft were used for restoration
      of normal venous return to the right atrium and alleviation of the cranial vena
      cava syndrome.

PMID- 15521442
TI  - Use of cyclosporine to treat granulomatous meningoencephalitis in three dogs.
AB  - Use of cyclosporine to treat granulomatous meningoencephalitis in three dogs
      Three dogs with a presumptive diagnosis of granulomatous meningoencephalitis were
      treated with orally administered cyclosporine. In 2 dogs, cyclosporine
      administration replaced initial corticosteroid administration, and in 1 dog,
      cyclosporine was the only treatment used. One dog had the focal form of the
      disease in the brainstem, 1 dog had the focal form in the forebrain associated
      with a concurrent ocular form, and 1 dog had the disseminated form of disease. At
      12-month follow-up, the 2 dogs with the focal form of the disease had no clinical
      signs. The dog with the disseminated form improved only partially, and euthanasia
      was performed 3 weeks after initial evaluation. Cyclosporine was considered
      effective at an initial dosage of 6 mg/kg (2.7 mg/lb) every 12 hours. Adverse
      effects associated with cyclosporine administration included transient
      lymphopenia, excessive shedding, and focal symmetric hair discoloration.

PMID- 15521443
TI  - Fracture of an endoluminal nitinol stent used in the treatment of tracheal
      collapse in a dog.
AB  - A 5-year-old castrated male Pomeranian was evaluated because of severe dyspnea
      and coughing, and a diagnosis of complete, static collapse of the trachea at the
      thoracic inlet was made. After failure to improve with medical management alone,
      an endoluminal tracheal stent was placed, which resulted in resolution of signs.
      Ten weeks after stent placement, the dog underwent tracheal resection and
      anastomosis because the stent had fractured at the level of the thoracic inlet.
      One year after surgery, the dog was doing well and required treatment with
      hydrocodone infrequently. Compared with other surgical treatment options,
      placement of an endoluminal tracheal stent is a relatively noninvasive
      intervention that can provide effective relief from the clinical signs associated
      with tracheal collapse in dogs. Implantation of endoluminal tracheal stents may
      be associated with complications; therefore, the procedure may best be regarded
      as a salvage procedure for dogs with end-stage disease that are refractory to
      appropriate medical management, have extensive collapse of the intrathoracic
      portion of the trachea, or are poor candidates for surgery.

PMID- 15521444
TI  - Double aortic arch in a dog.
AB  - Vascular ring anomalies are developmental anomalies of the thoracic great vessels
      resulting in complete or partial encircling of the esophagus and the trachea by a
      vascular ring formation. Persistent right aortic arch with left ligamentum
      arteriosum accounts for 95% of vascular ring anomalies in dogs. The dog in this
      report had a double aortic arch, which is a type 4 vascular ring anomaly. Double
      aortic arch is a rare congenital heart defect resulting from the improper
      development of the embryonic arches. The prognosis for dogs that have undergone
      surgery for correction of double aortic arches is generally regarded as poor. The
      dog in this report underwent surgery for correction of double aortic arches and
      recovered without dilation or motility disorders of the esophagus. Results
      indicate that small animals that undergo early surgical correction of double
      aortic arches with relief of esophageal constriction can have a good prognosis.
      To the authors' knowledge, there have been no previous reports of dogs that have
      survived long enough to be discharged from the hospital after surgical correction
      of double aortic arches.

PMID- 15521445
TI  - Massive hepatocellular carcinoma in dogs: 48 cases (1992-2002).
AB  - OBJECTIVE: To determine clinical signs, diagnostic findings, outcome, and
      prognostic factors in dogs treated surgically for massive hepatocellular
      carcinoma (HCC) and compare survival times of surgically and conservatively
      treated dogs. DESIGN: Retrospective study. ANIMALS: 48 dogs. PROCEDURE: Medical
      records were examined for clinical signs, diagnostic and surgical findings, and
      postoperative outcome. Dogs were allocated into surgery and nonsurgery groups
      depending on whether curative-intent liver lobectomy was performed. Data from the
      surgical and nonsurgical groups were analyzed to identify prognostic factors and
      determine and compare rates of tumor control and survival time. RESULTS: 42 dogs
      were treated surgically, and 6 were managed conservatively. In the surgery group,
      intraoperative mortality rate was 4.8% with no local recurrence, metastatic rate
      was 4.8%, and median survival time was > 1,460 days (range, 1 to 1,460 days).
      High alanine aminotransferase and aspartate aminotransferase activities were
      associated with poor prognosis. Median survival time for the nonsurgery group was
      270 days (range, 0 to 415 days), which was significantly less than that of
      surgically treated dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Liver lobectomy is
      recommended for dogs with massive HCC because tumor-related mortality rate was
      15.4 times higher in dogs in the nonsurgery group, compared with the surgery
      group. Tumor control was excellent after surgical resection with no local
      recurrence and a low metastatic rate. Prognostic factors were identified, but
      their clinical relevance was uncertain because only 9.5% of dogs in the surgery
      group died as a result of their disease.

PMID- 15521446
TI  - Risk factors for recurrence of clinical signs associated with thoracolumbar
      intervertebral disk herniation in dogs: 229 cases (1994-2000).
AB  - OBJECTIVE: To assess risk factors for recurrence of clinical signs associated
      with thoracolumbar intervertebral disk disease (IVDD) in dogs that had
      decompressive laminectomy without attempted prophylactic treatment of other disk
      spaces. DESIGN: Retrospective study. ANIMALS: 229 dogs. PROCEDURE: Medical
      records of dogs that had decompressive laminectomy without prophylactic
      fenestration for a first episode of IVDD and were available for follow-up were
      reviewed. Information on 7 clinical and 8 radiographic potential risk factors
      were recorded. RESULTS: Clinical signs associated with recurrence of IVDD
      developed in 44 (19.2%) dogs. Ninety-six percent of recurrences developed within
      3 years after surgery. Recurrence developed in 25% of Dachshunds and 15% of dogs
      of other breeds combined. Number of opacified disks was a significant risk factor
      for recurrence. Risk increased with number of opacified disks in an almost linear
      manner; each opacified disk increased risk by 1.4 times. Dogs with 5 or 6
      opacified disks at the time of first surgery had a recurrence rate of 50%.
      CONCLUSIONS AND CLINICAL RELEVANCE: When all likely episodes of recurrence are
      considered and a long follow-up period is achieved, true rate of recurrence of
      IVDD appears to be higher than in many previous reports. Dogs with multiple
      opacified disks at the time of first surgery should be considered a high-risk
      subpopulation.

PMID- 15521447
TI  - Use of low molecular weight heparin in cats: 57 cases (1999-2003).
AB  - OBJECTIVE: To determine duration of administration, complications, and frequency
      of aortic thromboembolism associated with administration of low molecular weight
      heparin (dalteparin) in cats. DESIGN: Retrospective study. ANIMALS: 57 cats
      treated with dalteparin PROCEDURE: Data were recorded from the medical records of
      cats treated with dalteparin, and owners were contacted by telephone for
      information regarding ease of administration and possible adverse effects.
      RESULTS: Dalteparin was easily administered by owners. Median dose was 99 U/kg
      (45 U/lb) once or twice daily. Bleeding complications were infrequent. Of 43 cats
      with cardiomyopathy that received owner-administered dalteparin for a median
      follow-up time of 172 days, 8 cats developed documented or possible arterial
      thromboembolism. CONCLUSIONS AND CLINICAL RELEVANCE: Dalteparin was easily
      administered by owners and was well tolerated by cats. Whether dalteparin
      administration can reduce the frequency or severity of arterial thromboembolism
      is not yet known.

PMID- 15521448
TI  - Perspective: the size-complexity rule.
AB  - It is widely accepted that bigger entities have a greater division of labor than
      smaller ones and this is reflected in the fact that larger multicellular
      organisms have a corresponding increase in the number of their cell types. This
      rule is examined in some detail from very small organisms to large animals, and
      plants, and societies. Compared to other size-related rules, the size-complexity
      rule is relatively rough and approximate, yet clearly it holds throughout the
      whole range of living organisms, as well as for societies. The relationship
      between size and complexity is analyzed by examining the effects of size increase
      and decrease: size increase requires an increase in complexity, whereas size
      decrease permits, and sometimes requires, a decrease in complexity. Conversely,
      an increase or decrease in complexity permits, but does not require changes in
      size. An especially compelling argument for the close relation between size and
      complexity can be found in size quorum sensing in very small multicellular
      organisms.

PMID- 15521449
TI  - Heterozygote excess in small populations and the heterozygote-excess effective
      population size.
AB  - It has been proposed that effective size could be estimated in small dioecious
      population by considering the heterozygote excess observed at neutral markers.
      When the number of breeders is small, allelic frequencies in males and females
      will slightly differ due to binomial sampling error. However, this excess of
      heterozygotes is not generated by dioecy but by the absence of individuals
      produced through selfing. Consequently, the approach can also be applied to self
      incompatible monoecious species. Some inaccuracies in earlier equations
      expressing effective size as function of the heterozygote excess are also
      corrected in this paper. The approach is then extended to subdivided populations,
      where time of sampling becomes crucial. When adults are sampled, the effective
      size of the entire population can be estimated, whereas when juveniles are
      sampled, the average effective number of breeders per subpopulations can be
      estimated. The main limitation of the heterozygote excess method is that it will
      only perform satisfactorily for populations with a small number of reproducing
      individuals. While this situation is unlikely to happen frequently at the scale
      of the entire population, structured populations with small subpopulations are
      likely to be common. The estimation of the average number of breeders per
      subpopulations is thus expected to be applicable to many natural populations. The
      approach is straightforward to compute and independent of equilibrium
      assumptions. Applications to simulated data suggest the estimation of the number
      of breeders to be robust to mutation and migration rates, and to specificities of
      the mating system.

PMID- 15521450
TI  - Incipient evolution of Wolbachia compatibility types.
AB  - Cytoplasmic incompatibility (CI) is induced in arthropods by the maternally
      inherited bacterium Wolbachia. When infected males mate with uninfected females
      or with females bearing a different Wolbachia variant, paternal chromosomes
      behave abnormally and embryos die. This pattern can be interpreted as resulting
      from two bacterial effects: One (usually termed mod, for modification) would
      affect sperm and induce embryo death, unless Wolbachia is also present in the
      egg, which implies the existence of a second effect, usually termed resc, for
      rescue. The fact that CI can occur in crosses between males and females infected
      by different Wolbachia shows that mod and resc interact in a specific manner. In
      other words, different compatibility types, or mod/resc pairs seem to have
      diverged from one (or a few) common ancestor(s). We are interested in the process
      allowing the evolution of mod/resc pairs. Here this question is addressed
      experimentally after cytoplasmic injection into a single host species (Drosophila
      simulans) by investigating compatibility relationships between closely related
      Wolbachia variants naturally evolving in different dipteran hosts: D. simulans,
      Drosophila melanogaster, and Rhagoletis cerasi. Our results suggest that closely
      related bacteria can be totally or partially incompatible. The compatibility
      relationships observed can be explained using a formal description of the mod and
      resc functions, implying both qualitative and quantitative variations.

PMID- 15521451
TI  - A reconciliation analysis of host switching in plant-fungal symbioses.
AB  - Plant-fungal symbioses include many familiar antagonistic and mutualistic
      associations and some model cases of coevolution. The relationship between
      coevolution at the different evolutionary scales has remained an open question.
      Widespread host specificity and documented host switches offer conflicting
      indications of what to expect from comparisons of plant and fungal phylogenies.
      This study sought to establish the role of plant phylogeny in determining fungal
      phylogeny and the relative contributions of codivergence and host switching by
      comparing tree topologies for 15 plant-fungal symbioses. Second it attempted to
      characterize the relationship between phylogenetic congruence and switching.
      Trees were estimated from published sequences and reconciliation analysis was
      applied in the form of cophylogeny mapping using "jungles". This provided an
      exhaustive account of all possible switches capable of reconciling two associated
      phylogenies. A continuum of cophylogenetic dynamics was identified, ranging from
      mostly codivergence (e.g., Exobasidium) to mostly switching, (e.g., Erysiphe).
      Surprisingly, congruent solutions do not necessarily have fewer switches when
      using cophylogeny mapping, but a significant negative relationship between
      congruence and the distance of switches proved to be a useful indicator.
      According to reconciliation analysis, the contribution of host phylogeny varies
      widely across plant-fungal symbioses, making host specificity and coadaptation
      poor indicators of macroevolutionary trends because they are necessary, but not
      sufficient, conditions.

PMID- 15521452
TI  - On the evolutionary costs of self-incompatibility: incomplete reproductive
      compensation due to pollen limitation.
AB  - Pollen limitation affects plants with diverse reproductive systems and ecologies.
      In self-incompatible (SI) species, pollen limitation may preclude full
      reproductive compensation for prezygotic rejection of pollen. We present a model
      designed to explore the effects of incomplete reproductive compensation on
      evolutionary changes at a modifier locus that regulates the level of SI
      expression. Our results indicate that incomplete reproductive compensation
      greatly increases the evolutionary costs of SI, particularly in populations with
      low S-allele diversity. The evolutionary fate of modifiers of SI expression
      depends on the rate at which they are transmitted to future generations as well
      as the effects of SI on offspring number and quality. Partial SI expression can
      represent a stable condition rather than an evolutionarily transient state
      between full expression and full suppression. This unanticipated result provides
      the first theoretical support for the evolutionary stability of such mixed mating
      systems, the existence of which has recently been documented.

PMID- 15521453
TI  - Genetic constraints on floral evolution in a sexually dimorphic plant revealed by
      artificial selection.
AB  - Sexual dimorphism is one of the most widespread and recognizable patterns of
      phenotypic variation in the biotic world. Sexual dimorphism in floral display is
      striking in the dioecious plant Silene latifolia, with males making many, small
      flowers compared to females. We investigated this dimorphism via artificial
      selection on two populations to determine whether genetic variation exists within
      populations for flower size and the extent of the between-sex correlation,
      whether a flower size and number trade-off exists within each sex, and whether
      pollen and ovule production vary with flower size. We selected for decreased
      flower size (calyx width) in females and increased flower size in males and
      measured the response to selection in size and correlated responses in flower dry
      mass, flower number, and pollen or ovule number per flower. Four bouts of
      selection in each of two selection programs were performed, for a total of three
      selection lines to decrease size, three to increase it, and two control lines.
      Flower size always significantly responded to selection and we always found a
      significant correlated response in the sex not under selection. Selection
      decreased but did not eliminate the sexual dimorphism in flower dry mass and
      number. A negative relationship between flower size and number within each sex
      was revealed. Whereas ovule number showed a significant correlated response to
      selection on flower size, pollen number did not. Our results indicate that
      although substantial additive genetic variation for flower size exists, the high
      between-sex genetic correlation would likely constrain flower size from becoming
      more sexually dimorphic. Furthermore, floral display within each sex is
      constrained by a flower size and number trade-off. Given this trade-off and lack
      of variation in pollen production with flower size, we suggest that sexual
      dimorphism evolved via sexual selection to increase flower number in males but
      not females.

PMID- 15521454
TI  - Rapid divergent evolution of sexual morphology: comparative tests of antagonistic
      coevolution and traditional female choice.
AB  - Male structures specialized to contact females during sexual interactions often
      diverge relatively rapidly over evolutionary time. Previous explanations for this
      pattern invoked sexual selection by female choice, but new ideas emphasize
      possible sexually antagonistic coevolution resulting from male-female conflict
      over control of fertilization. The two types of selection have often not been
      carefully distinguished. They do not theoretically exclude one another, but they
      have not necessarily had equally important roles in producing rapid evolutionary
      divergence. To date, most recent empirical studies of antagonistic coevolution
      have emphasized only a few taxa. This study uses the abundant but little-used
      data in the taxonomic literature on morphology to evaluate the roles of
      antagonistic coevolution and traditional female choice over a wide taxonomic
      spectrum (61 families of arthropods, mostly insects and spiders). Groups with
      species-specific male structures that contact females were checked for
      coevolution of species-specific female structures that are contacted by the male
      and that have mechanical properties that could potentially defend her against the
      male. Facultatively deployable, species-specific female defensive structures, a
      design that would seem likely to evolve frequently under the sexually
      antagonistic coevolution hypothesis, were completely absent (0% of 106 structures
      in 84 taxonomic groups). Although likely cases of sexually antagonistic
      coevolution exist, using conservative criteria, 79.2% of the 106 structures
      lacked even potentially defensive female coevolution. A common pattern (53.8% of
      106) was a nearly complete absence of female change in areas contacted by species
      specific male structures. Post-hoc arguments invoking possible coevolution of
      defensive female behavior instead of morphology, or of female sensitivities and
      responses to male sensory traps, could enable the sexually antagonistic
      coevolution hypothesis to explain these data. No case of such coevolution of
      female behavior or sensitivities has been demonstrated, and there are additional
      reasons to doubt that they are general explanations for the data presented here.
      Detailed studies of female resistance behavior could help illuminate several
      issues. The possibility of a greater role for antagonistic coevolution in
      reproductive physiology than in morphology and the possibility that female choice
      and sexually antagonistic coevolution have both been important in some lineages
      are discussed.

PMID- 15521455
TI  - Ecomorphological adaptation of acorn weevils to their oviposition site.
AB  - Comparisons between closely related species in different habitats provide a
      window into understanding how biotic factors shape evolutionary pathways. Weevils
      in the genus Curculio have radiated extensively across the Palearctic, where
      similar ecomorphs have evolved independently on different hosts. We examined
      ecological and morphological data for 31 Curculio species using multivariate
      statistics to determine which morphological traits covary and which correlate
      with the host seed size. A subset of 15 taxa for which phylogenetic relationships
      were known were used for comparative analyses and inferring historical patterns
      of trait evolution. The morphological analyses suggest rostrum size increased
      proportionately to body size in both males and females and that both rostrum and
      body size correlate with host seed size but that rostrum shape does not correlate
      with any of the seed traits used in the analyses. Host shifts from small seeds to
      considerably larger seeds or vice versa have occurred several times independently
      and historical trait evolution indicates that these host shifts were accompanied
      by morphological changes in rostrum size. These patterns suggest that seed size
      is an important selective agent for changes in rostrum length along with body
      size and thus may be a key factor promoting morphological differentiation in the
      genus Curculio.

PMID- 15521456
TI  - Evolutionary rates in the adaptive radiation of beetles on plants.
AB  - Herbivorous insects and other small consumers are often specialized both in use
      of particular host taxa and in use of particular host tissues. Such consumers
      also often seem to show consistent differences in the rates of evolution of these
      two dimensions of host use, implying common processes, but this has been little
      studied. Here we quantify these rates of change in host use evolution in a major
      radiation of herbivorous insects, the Chrysomeloidea, whose diversity has been
      attributed to their use of flowering plants. We find a significant difference in
      the rates of evolutionary change in these two dimensions of host use, with host
      taxon associations most labile. There are apparently similar differences in rates
      of host use evolution in other parasite groups, suggesting the generality of this
      pattern. Divergences in parasite form associated with use of different host
      tissues may facilitate resource partitioning among successive adaptive radiations
      on particular host taxa.

PMID- 15521457
TI  - Shifting patterns in genetic control at the embryo-alevin boundary in brook
      charr.
AB  - Maternal inputs to offspring early in development are initially high but the
      process of development suggests that ontogenetic shifts in the importance of
      maternal genetic variation relative to other sources should occur. We
      investigated additive genetic variance and covariance for direct (animal), sire,
      and maternal effects on embryonic length (EL), yolk sac volume (YSV), and alevin
      (after yolk sac resorption) length (AL) for 460 embryonic and 460 alevin brook
      charr (Salvelinus fontinalis) in 23 half-sib families (12 sires, 23 dams). There
      were no additive genetic effects of sires or individual animals on their own
      phenotype using sire-dam and maternal-animal models for YSV or EL (h(a)2 < 0.05).
      However, at the alevin stage we detected low but significant heritability for AL
      (h(a)2 = 0.14 +/- 0.11). Conversely, maternal genetic effects were high for both
      embryonic traits (h(EL)2 = 0.61 +/- 0.05; h(YSU)2 = 0.57 +/- 0.06) but faded
      rapidly for postresorption length (h(AL)2 = 0.18 +/- 0.04). Maternal effects in
      the sire-dam model corresponded highly with those in the animal-dam model. We did
      not detect significant genetic covariance between progeny and dams for
      preresorption traits or between sires and dams for any trait. However, following
      resorption of the yolk sac, the genetic value of dams for AL was negatively
      correlated with that of individual progeny (r(m,a) = -0.38 +/- 0.13), suggesting
      trade-offs and/or stabilizing selection between maternal and animal genetic trait
      value. This finding was supported by models of dam fecundity on offspring length
      and dam weight in phenotypic space. Heritability estimates using simple
      regression of embryo phenotype on adult parental phenotype produced upwardly
      biased estimates of genetic variance (h2 > 1.0). We propose that development
      through the embryo-alevin boundary may be a major point in salmonids for
      ontogenetic changes in the genetic architecture of embryo size from maternal
      genetic effects to those of the individual organism, and that maternal-offspring
      conflicts in resource allocation related to size may be partially indicated by
      negative genetic covariance.

PMID- 15521458
TI  - Population differentiation in G matrix structure due to natural selection in Rana
      temporaria.
AB  - The additive genetic variance-covariance matrix (G) is a concept central to
      discussions about evolutionary change over time in a suite of traits. However, at
      the moment we do not know how fast G itself changes as a consequence of selection
      or how sensitive it is to environmental influences. We investigated possible
      evolutionary divergence and environmental influences on G using data from a
      factorial common-garden experiment where common frog (Rana temporaria) tadpoles
      from two divergent populations were exposed to three different environmental
      treatments. G-matrices were estimated using an animal model approach applied to
      data from a NCII breeding design. Matrix comparisons using both Flury and
      multivariate analysis of variance methods revealed significant differences in G
      matrices both between populations and between treatments within populations, the
      former being generally larger than the latter. Comparison of levels of population
      differentiation in trait means using Q(ST) indices with that observed in
      microsatellite markers (F(ST)) revealed that the former values generally exceeded
      the neutral expectation set by F(ST). Hence, the results suggest that
      intraspecific divergence in G matrix structure has occurred mainly due to natural
      selection.

PMID- 15521459
TI  - Genetic analysis of complex demographic scenarios: spatially expanding
      populations of the cane toad, Bufo marinus.
AB  - Inferring the spatial expansion dynamics of invading species from molecular data
      is notoriously difficult due to the complexity of the processes involved. For
      these demographic scenarios, genetic data obtained from highly variable markers
      may be profitably combined with specific sampling schemes and information from
      other sources using a Bayesian approach. The geographic range of the introduced
      toad Bufo marinus is still expanding in eastern and northern Australia, in each
      case from isolates established around 1960. A large amount of demographic and
      historical information is available on both expansion areas. In each area,
      samples were collected along a transect representing populations of different
      ages and genotyped at 10 microsatellite loci. Five demographic models of
      expansion, differing in the dispersal pattern for migrants and founders and in
      the number of founders, were considered. Because the demographic history is
      complex, we used an approximate Bayesian method, based on a rejection-regression
      algorithm, to formally test the relative likelihoods of the five models of
      expansion and to infer demographic parameters. A stepwise migration-foundation
      model with founder events was statistically better supported than other four
      models in both expansion areas. Posterior distributions supported different
      dynamics of expansion in the studied areas. Populations in the eastern expansion
      area have a lower stable effective population size and have been founded by a
      smaller number of individuals than those in the northern expansion area. Once
      demographically stabilized, populations exchange a substantial number of
      effective migrants per generation in both expansion areas, and such exchanges are
      larger in northern than in eastern Australia. The effective number of migrants
      appears to be considerably lower than that of founders in both expansion areas.
      We found our inferences to be relatively robust to various assumptions on marker,
      demographic, and historical features. The method presented here is the only
      robust, model-based method available so far, which allows inferring complex
      population dynamics over a short time scale. It also provides the basis for
      investigating the interplay between population dynamics, drift, and selection in
      invasive species.

PMID- 15521460
TI  - Inbreeding in the Seychelles warbler: environment-dependent maternal effects.
AB  - The deleterious effects of inbreeding can be substantial in wild populations and
      mechanisms to avoid such matings have evolved in many organisms. In situations
      where social mate choice is restricted, extrapair paternity may be a strategy
      used by females to avoid inbreeding and increase offspring heterozygosity. In the
      cooperatively breeding Seychelles warbler, Acrocephalus sechellensis, neither
      social nor extrapair mate choice was used to avoid inbreeding facultatively, and
      close inbreeding occurred in approximately 5% of matings. However, a higher
      frequency of extra-group paternity may be selected for in female subordinates
      because this did reduce the frequency of mating between close relatives.
      Inbreeding resulted in reduced individual heterozygosity, which, against
      expectation, had an almost significant (P = 0.052), positive effect on survival.
      Conversely, low heterozygosity in the genetic mother was linked to reduced
      offspring survival, and the magnitude of this intergenerational inbreeding
      depression effect was environment-dependent. Because we controlled for genetic
      effects and most environmental effects (through the experimental cross-fostering
      of nestlings), we conclude that the reduced survival was a result of maternal
      effects. Our results show that inbreeding can have complicated effects even
      within a genetic bottlenecked population where the "purging" of recessive alleles
      is expected to reduce the effects of inbreeding depression.

PMID- 15521461
TI  - Song learning accelerates allopatric speciation.
AB  - The songs of many birds are unusual in that they serve a role in identifying
      conspecific mates, yet they are also culturally transmitted. Noting the
      apparently high rate of diversity in one avian taxon, the songbirds, in which
      song learning appears ubiquitous, it has often been speculated that cultural
      transmission may increase the rate of speciation. Here we examine the possibility
      that song learning affects the rate of allopatric speciation. We construct a
      population-genetic model of allopatric divergence that explores the evolution of
      genes that underlie learning preferences (predispositions to learn some songs
      over others). We compare this with a model in which mating signals are inherited
      only genetically. Models are constructed for the cases where songs and
      preferences are affected by the same or different loci, and we analyze them using
      analytical local stability analysis combined with simulations of drift and
      directional sexual selection. Under nearly all conditions examined, song
      divergence occurs more readily in the learning model than in the nonlearning
      model. This is a result of reduced frequency-dependent selection in the learning
      models. Cultural evolution causes males with unusual genotypes to tend to learn
      from the majority of males around them, and thus develop songs compatible with
      the majority of the females in the population. Unusual genotypes can therefore be
      masked by learning. Over a wide range of conditions, learning therefore reduces
      the waiting time for speciation to occur and can be predicted to accelerate the
      rate of speciation.

PMID- 15521462
TI  - Differential patterns of introgression across the X chromosome in a hybrid zone
      between two species of house mice.
AB  - A complete understanding of the speciation process requires the identification of
      genomic regions and genes that confer reproductive barriers between species.
      Empirical and theoretical research has revealed two important patterns in the
      evolution of reproductive isolation in animals: isolation typically arises as a
      result of disrupted epistatic interactions between multiple loci and these
      disruptions map disproportionately to the X chromosome. These patterns suggest
      that a targeted examination of natural gene flow between closely related species
      at X-linked markers with known positions would provide insight into the genetic
      basis of speciation. We take advantage of the existence of genomic data and a
      well-documented European zone of hybridization between two species of house mice,
      Mus domesticus and M. musculus, to conduct such a survey. We evaluate patterns of
      introgression across the hybrid zone for 13 diagnostic X-linked loci with known
      chromosomal positions using a maximum likelihood model. Interlocus comparisons
      clearly identify one locus with reduced introgression across the center of the
      hybrid zone, pinpointing a candidate region for reproductive isolation. Results
      also reveal one locus with high frequencies of M. domesticus alleles in
      populations on the M. musculus side of the zone, suggesting the possibility that
      positive selection may act to drive the spread of alleles from one species on to
      the genomic background of the other species. Finally, cline width and cline
      center are strongly positively correlated across the X chromosome, indicating
      that gene flow of the X chromosome may be asymmetrical. This study highlights the
      utility of natural populations of hybrids for mapping speciation genes and
      suggests that the middle of the X chromosome may be important for reproductive
      isolation between species of house mice.

PMID- 15521463
TI  - The evolution of gene expression in mouse hippocampus in response to selective
      breeding for increased locomotor activity.
AB  - The evolution of behavior has been notoriously difficult to study at the
      molecular level, but mouse genetic technology offers new promise. We applied
      selective breeding to increase voluntary wheel running in four replicate lines of
      Mus domesticus (S mice) while maintaining four additional lines through random
      breeding to serve as controls (C mice). The goal of the study was to identify the
      gene expression profile of the hippocampus that may have evolved to facilitate
      the increased voluntary running. The hippocampus was of interest because it is
      known to display marked physiological responses in association with wheel running
      itself. We used high-density oligonucleotide arrays representing 11,904 genes. To
      control for the confounding influence of physical activity itself on gene
      expression, animals were housed individually without access to running wheels,
      and were sampled during the day when they are normally inactive. Two-month-old
      female mice in estrus were used (n = 16 total; two per line; 8 S and 8 C). After
      correcting for an acceptable false discovery rate (10%), 30 genes, primarily
      involved in transcription and translation, significantly increased expression
      whereas 23 genes, distributed among many categories including immune function and
      neuronal signaling, decreased expression in S versus C mice. These changes were
      relatively small in magnitude relative to the changes in gene expression that
      occur in the hippocampus in response to wheel running itself. A priori tests of
      dopamine receptor expression levels demonstrated an increase of approximately 20%
      in the expression of D2 and D4 receptors. These results suggest that relatively
      small changes in the expression patterns of hippocampal genes underlie large
      changes in phenotypic response to selection, and that the genetic architecture of
      running motivation likely involves the dopaminergic system as well as CNS
      signaling machinery.

PMID- 15521464
TI  - Exploring the relationship between parental relatedness and male reproductive
      success in the Antarctic fur seal Arctocephalus gazella.
AB  - Recent genetic studies of natural populations have shown that heterozygosity and
      other genetic estimates of parental relatedness correlate with a wide variety of
      fitness traits, from juvenile survival and parasite resistance to male
      reproductive success. Many of these traits involve health and survival, where the
      underlying mechanism may involve changes in the effectiveness of the immune
      system. However, for traits such as reproductive success, the likely mechanisms
      remain less obvious. In this paper, we examine the relationship between
      heterozygosity and a range of traits that contribute to male reproductive
      success, including time spent on territories and competitiveness. Our analysis is
      based on observational and genetic data from eight consecutive breeding seasons
      at a colony of the Antarctic fur seal, Arctocephalus gazella. Overall, male
      reproductive success was found to correlate strongly with internal relatedness
      (IR, a form of heterozygosity). When different components of success were
      analyzed, we found that IR correlates independently with reproductive longevity,
      time spent ashore, and competitive ability per unit mating opportunity on the
      study beach, with more heterozygous males being more successful. Behavioral
      observations were sufficiently detailed to allow examination of how daily mean IR
      values for males present on the beach varied within seasons and from year to
      year. Again, significant variation was found both among and within seasons, with
      more homozygous males appearing less able to hold territories in poor seasons
      when pup production is low and, within a season, at both the start of the season
      and to some extent around the peak of female estrus. Finally, we tested whether
      the benefits of high heterozygosity are due mainly to a genomewide effect (e.g.
      inbreeding depression) or to single locus heterosis by asking whether the
      relationship between IR and male success was robust to the removal of any single
      locus or to any pair of loci. Since the relationship remained significant in all
      cases, we favor a multilocus explanation for the effects we report.

PMID- 15521465
TI  - Fractal geometry is heritable in trees.
AB  - Understanding the genetic basis to landscape vegetation structure is an important
      step that will allow us to examine ecological and evolutionary processes at
      multiple spatial scales. Here for the first time we show that the fractal
      architecture of a dominant plant on the landscape exhibits high broad-sense
      heritability and thus has a genetic basis. The fractal architecture of trees is
      known to influence ecological communities associated with them. In a
      unidirectional cottonwood-hybridizing complex (Populus angustifolia x P.
      fremontii) pure and hybrid cottonwoods differed significantly in their fractal
      architecture, with phenotypic variance among backcross hybrids exceeding that of
      F1 hybrids and of pure narrowleaf cottonwoods by two-fold. This result provides a
      crucial link between genes and fractal scaling theory, and places the study of
      landscape ecology within an evolutionary framework.

PMID- 15521466
TI  - The developmental bases of limb reduction and body elongation in squamates.
AB  - Employing an integrative approach to investigate the evolution of morphology can
      yield novel perspectives not attainable from a single field of study. Studies of
      limb loss and body elongation in squamates (snakes and lizards) present a good
      example in which integrating studies of systematics and ecology with genetics and
      development can provide considerable new insight. In this comment we address
      several misunderstandings of the developmental genetic literature presented in a
      paper by Wiens and Slingluff (2001) to counter their criticism of previous work
      in these disciplines and to clarify the apparently contradictory data from
      different fields of study. Specifically, we comment on (1) the developmental
      mechanisms underlying axial regionalization, body elongation, and limb loss; (2)
      the utility of presacral vertebral counts versus more specific partitioning of
      the primary body axis; (3) the independent, modular nature of limbs and limb
      girdles and their utility in diagnosing genetic changes in development; and (4)
      the causal bases of hind limb reduction in ophidian and nonophidian squamates.

PMID- 15521467
TI  - Continuous EEG monitoring in the intensive care unit.
AB  - It is now feasible and desirable to continuously monitor brain function with EEG
      in critically ill patients. Nonconvulsive seizures are more common than
      previously recognized and may contribute to impaired mental status and brain
      injury. Alerting stimuli commonly elicit periodic or ictal-appearing EEG
      patterns. Cerebral ischemia can be detected at a reversible stage with continuous
      EEG monitoring (cEEG). With the current availability of treatments for acute
      ischemia, this early detection has great potential for the prevention of stroke,
      but is only now beginning to be utilized for this purpose. The intensive care
      unit poses many technical difficulties for EEG acquisition, and artifact
      recognition is more important than ever. Recording synchronized video with EEG is
      essential for maximizing the efficiency and accuracy of cEEG interpretation, and
      quantitative EEG analysis can be quite helpful. The role of the EEG technologist
      is particularly important in these patients to aid in recognizing and minimizing
      artifact, to enhance communication between electroencephalographers and
      clinicians, to assess the effect of alerting stimuli, and to note possible subtle
      clinical correlates of electrographic seizures.

PMID- 15521468
TI  - Quality assurance in determinations of brain death.
AB  - A 2002 study (Wang et al.) revealed the need to increase quality assurance (QA)
      activities to improve the declaration and documentation of brain death, thus
      improving the opportunity and potential for organ and tissue donation. One aspect
      of the QA concept is to provide checklists and training to physicians and
      hospital staff involved. Training will ensure that all personnel are sensitive to
      the complex process of brain death and the many diverse issues prevalent today.
      Checklists may be used to exclude other conditions or causes of irreversible coma
      and to verify the lack of appropriate reflexes in such patients.
      Electroneurodiagnostic (END) technologists may be asked to perform confirmatory
      tests in cases of suspected brain death, such as the EEG for electrocerebral
      inactivity (ECI), or the brainstem auditory or somatosensory evoked potentials. A
      look at published Guidelines will help ensure that END technologists perform
      these tests correctly. A solid understanding of the process ensures that
      diagnostic and technical mistakes are avoided and may provide helpful guidance to
      all involved. This paper also includes a brief look at some other available
      confirmatory tests, as well as some of the ethical issues involved.

PMID- 15521469
TI  - Computer technology and networking for the neurodiagnostic and sleep laboratory.
AB  - The purpose of this article is to help those in neurodiagnostics and in sleep
      diagnostics have a better understanding of the technology that is available when
      purchasing new equipment for the laboratory. With the rapid advancements within
      the computer industry, neurodiagnostic and sleep equipment companies are using
      those newer technologies in the development of diagnostic systems. Having a good
      understanding of the technology utilized certainly helps those making equipment
      purchases be better versed during the process. With constraints on capital
      equipment purchases, it is important to maximize the budget so the laboratory can
      be equipped with the best instrumentation available.

PMID- 15521470
TI  - Otoacoustic emissions.
AB  - Congenital hearing impairment has adverse effects on speech and language
      acquisition as well as on emotional and intellectual development. It has been
      confirmed that these effects are reduced when recognition and intervention in the
      case of hearing impairment occur before the age of six months. Otoacoustic
      emissions (OAEs) are vibrations created by contractions of the outer haircells
      that are located in the cochlea. It is hypothesized that outer- hair cell
      contraction follows inner hair cell stimulation, thus enhancing the spatial
      resolution of the cochlea. The identification and recognition of sounds of
      different frequency is thereby amplified. The outer hair cell contraction
      generates a vibration within the cochlea that is retrogradely transduced to the
      middle ear. There, it is transduced by the ossicles to the eardrum, that is
      brought to vibration. These vibrations create sounds that can be recorded in the
      ear canal. These sounds are soft, but potentially audible, infrequently amounting
      to as much as 30 dB SPL. For detection of these OAEs, normal middle ear function
      is mandatory. OAEs are generated only when the organ of Corti is in normal or
      near normal condition and their presence, therefore, is indicative of normal
      middle ear and cochlear function. OAEs may emerge spontaneously, but more
      commonly follow acoustic stimulation as described above.

PMID- 15521471
TI  - Standardized mental status testing for nonconvulsive status epilepticus.

PMID- 15521472
TI  - Digital filters.

PMID- 15521473
TI  - [The French Society of Cardiology and recommendations of good practice].

PMID- 15521474
TI  - [Management of heart failure by French general practitioners in 2003].
AB  - The PRINCEPS study (Prise en charge des Insuffisants Cardiaques: Enquete chez les
      Patients Symptomatiques) was carried out by 1,717 general practitioners who
      reported their experience with 3,782 patients with cardiac failure treated by an
      angiotensin converting enzyme (ACE) inhibitor. This is the largest observational
      study carried out in general practice in France to date. The average age of the
      patients with cardiac failure was 71 years, with a majority of men (62%), many of
      whom were hypertensive (76%) and had other cardiovascular risk factors. The
      diagnosis of cardiac failure was made by the presence of effort dyspnoea (92%)
      and confirmed by a cardiologist in 81% of cases. Heart failure was rarely chronic
      (17%>5 years), usually related to hypertension (58%) and had required hospital
      admission in only 39% of patients. Finally, the patients were not very
      symptomatic (63% Class II of the NYHA Classification). Treatment included the
      obligatory ACE inhibitor at a high dosage (maximal dosage according the European
      Recommendations) in half the patients. The dosage prescribed was considered
      optimal in 3 out of 4 patients, and usually treated by the consulting
      cardiologist (81% of patients). It was higher in the young patients, less
      symptomatic, and in patients with heart failure due to hypertension. A treatment
      with betablockers (20%), diuretics (74%), digitalis (21%), was often associated
      with the ACE inhibitor. These results suggest that heart failure patients treated
      by general practitioners have hypertension as the main cause. The ACE inhibitors
      seem to be prescribed initially at high dosage for treating the hypertension, and
      the dosage is progressively decreased with time and aggravation of the cardiac
      failure.

PMID- 15521475
TI  - [Management of the cardiology patient with polyvascular disease: PRISMA study].
AB  - INTRODUCTION: Myocardial infarction (MI), peripheral vascular disease and
      ischaemic cerebral vascular accident (CVA) are three manifestations of the same
      disease, atherothrombosis, and they share the same pathophysiology and prognosis.
      OBJECTIVE: The aim of this work was to describe the clinical characteristics and
      the medical management of polyvascular patients in cardiology. METHOD:
      Cardiologists from all over the country participated in a consultation register
      for 3 weeks. The clinical characteristics and medical management for the first 3
      patients on the register for each cardiologist were studied in a national
      multicentre study and then compared according to whether the atherothrombotic
      disease was isolated or polyvascular. RESULTS: In total, 100,429 patients were
      examined during the period of the register and 2,780 were included in the study.
      Polyvascular patients represented 7% of the register and 22% of the vascular
      patients. These patients with multiple manifestations were frequently diabetics.
      A lipid profile was available less often in the cardiac patients when they had
      another disorder (72.4%) than in the case of an isolated disorder (78.9%).
      Whatever the initial disorder, dyslipidaemia was less often controlled in the
      case of polyvascular disease (63% of LDL-C > or = 1.3g/l in polyvascular cardiac
      patients vs 52% in cardiac patients with isolated disease). In cardiac patients,
      the presence of peripheral vascular disease was associated with less prescription
      of beta blockers (OR=0.4 [0.3-0.6]), the presence of CVA was associated with less
      prescription of statins (OR=0.7 [0.5-0.9]). Eight out of 10 polyvascular patients
      received anti-platelet aggregation treatment. The presence of multiple
      atherothrombotic manifestations was associated with greater prescription of ACEI,
      except in cardiac patients. CONCLUSION: These results improve our understanding
      of the specific management of polyvascular patients, for whom secondary
      prevention is paramount due to the higher risk of recurrence. They should prompt
      the reinforcement of measures which have been shown to be effective, such as
      managing major risk factors, and in particular the dislipidaemias.

PMID- 15521476
TI  - Cumulative adverse effects of diabetes mellitus and hypertension on coronary flow
      velocity reserve.
AB  - BACKGROUND: this study aimed to assess the hypothesis that essential hypertension
      (EH) may increase coronary microcirculation dysfunction in patients with type 2
      diabetes mellitus (DM). Microvascular dysfunction has been reported in patients
      with DM or EH. Discordant results have been reported on cumulative adverse
      effects of the simultaneous presence of DM and EH on coronary flow velocity
      reserve (CFR). METHODS: CFR were compared in 13 hypertensive diabetics (group 1),
      12 normotensive diabetics (group 2), 11 hypertensive non diabetics (group 3) and
      29 normotensive non diabetic patients (group 4). CFR was calculated using an
      intracoronary Doppler-tipped flow wire. RESULTS: CFR was significantly lower in
      patients with both DM and EH (2.2 +/- 0.4 in group 1 vs 2.8 +/- 0.5, 2.8 +/- 0.6
      and 2.9 +/- 0.7 in groups 2, 3 and 4 respectively, p<0.01). The presence of
      hypertension reduced CFR in diabetic patients with angiographically abnormal but
      unobstructed coronary arteries (2.1 +/- 0.3 in hypertensive vs 3.1 +/- 0.2 in
      normotensive diabetic patients, p<0.02). No cumulative adverse effect was
      observed in diabetics with angiographically normal coronary arteries (2.3 +/- 0.6
      in hypertensive vs 2.6 +/- 0.5 in normotensive diabetic patients, NS).
      Multivariate analysis revealed that combination of DM and EH (p<0.007) was
      independently related to CFR. CONCLUSIONS: the presence of hypertension appears
      to worsen coronary microangiopathy in diabetic patients with unobstructed
      coronary artery disease. The cumulative effect of EH and DM on CFR impairment has
      consequences for decision-making during coronary angioplasty and could identify
      patients at risk for cardiomyopathy.

PMID- 15521477
TI  - [Medical histories of patients with Marfan's syndrome].
AB  - The life expectancy of patients with Marfan's syndrome has been increased by over
      30 years by modern medico-surgical management but the diagnostic problems related
      to the multiplicity of symptoms and the necessity of collaboration by many
      specialities complicate the medical history of patients, which is largely
      unknown. The authors sent a self-administered questionnaire to 1 353 patients
      with Marfan's syndrome to obtain this information. Of the 430 questionnaires
      returned, as many by men as by women, the diagnosis of the disease was made in
      less than half the cases by clinical symptoms (42%): the investigation of an
      unrelated clinical problem (39%) or a family enquiry (19%) also led to the
      diagnosis. The delay between the first symptoms of the disease and first medical
      consultation (usually cardiological or ophthalmic) was long (5.2 years) as was
      the interval between the first consultation and the diagnosis (2.8 years).
      However, the population could be divided into two groups. one with rapid access
      to the physician (< 1 year) and to the diagnosis (< 3 years) and the second group
      in which the delays are long. When the diagnosis of Marfan's syndrome is made
      following consultation for an unrelated condition, it is more often delayed and
      the patient is usually older. The delay in diagnosis observed could be shortened
      by systematic familial enquiries and better information to physicians who could
      then suspect the diagnosis before the advent of clinical symptoms.

PMID- 15521479
TI  - [Predictive value of aortic atherosclerosis detected by transoesophageal
      echocardiography for the presumption of coronary artery disease].
AB  - The aim of this study was to determine the relationship between plaques of aortic
      atheroma detected by transoesophageal echocardiography and the condition of the
      coronary arteries at coronary angiography. Two hundred and seventeen consecutive
      patients were included for systematic transoesophageal echocardiography blinded
      to the results of coronary angiography. Significant coronary disease was defined
      as stenosis of at least 70% of the artery lumen. Aortic atherosclerosis was
      classified in four grades. The average age of the patients was 54.5 +/- 10.5
      years. The sex ratio was 2.55 in favour of men. The average coronary score was 5
      +/- 4.5 and the lesion index was 1.1 +/- 0.96. One hundred and fifty-nine
      patients had aortic atheroma, 73% of which (80 cases) were complex lesions. The
      descending aorta was the commonest site (91%) followed by the transverse (40% and
      ascending aorta (14%). When the ascending aorta was affected there was a very
      significant association with coronary artery disease (100% of cases). Sixty-one
      per cent of patients had lesions of one aortic segment, 28% had lesions of two
      aortic segments and in 10%, all three aortic segments were involved. The presence
      of aortic atheroma was correlated with coronary artery disease with a sensitivity
      and specificity of 86% and 76% respectively. The positive and negative predictive
      values were 81% and 31% respectively. Seventy-five per cent of patients with a
      coronary score of at least 7 had aortic atheroma with complex lesions in 47% of
      cases. The lesion index was significantly higher in this group when the coronary
      score was less than 7 (1.98 +/- 0.8 vs 0.65 +/- 0.7, p<0.00001). Patients with
      coronary artery disease have more complex lesions of the descending than of the
      ascending aorta (94 vs 25%). Significant coronary artery disease was correlated
      with the presence of aortic atheroma, especially of the ascending aorta. The
      specificity and positive predictive values were 100% but the negative predictive
      value was poor, irrespective of the aortic segment involved (32% for the
      ascending aorta, 36% for the transverse and 35% for the descending aorta). The
      authors conclude that transoesophageal echocardiography of the thoracic aorta is
      a good method of predicting severe coronary atherosclerotic disease.

PMID- 15521478
TI  - [Angioplasty of saphenous vein grafts in the acute phase of myocardial
      infarction. Short and mid-term results].
AB  - The impact of the progress of interventional cardiology on the improved prognosis
      of myocardial infarction due to occlusion of a saphenous vein bypass graft is not
      well known. The aim of this study was to report the modalities and results at
      short and medium term of revascularisation by angioplasty of venous grafts in the
      acute phase of myocardial infarction. Out of a total of 870 consecutive patients
      treated by angioplasty in the first 6 hours of myocardial infarction with
      persistent ST elevation between 1990 and 2002, 16 (2%) had acute occlusion of a
      saphenous vein graft. Twelve of the 16 patients had previous myocardial
      infarction; perfusion was obtained in 7 patients. The attempt failed in 9
      patients because of "no-reflow" (n=5), the extensive nature of the thrombosis
      (n=2) and technical failure (n=2). Three patients died in hospital, all after
      failed angioplasty. At 6 months, of the 13 survivors of the hospital period, 2
      had been readmitted for a revascularisation procedure. At 2 years, 3 patients had
      died, 2 were readmitted for recurrent myocardial infarction and 8 patients
      remained free of a major cardiovascular event. Reperfusion by angioplasty of an
      occluded saphenous vein graft in the acute phase of myocardial infarction remains
      imperfect and the prognosis at short and medium term is poor.

PMID- 15521480
TI  - [Widening plasty of the anterior cusp in rheumatic mitral insufficiency].
AB  - The mechanism of insufficiency in rheumatic valve disease includes 1. annulus
      dilatation and 2. restricted leaflet motion. Aiming at improving the treatment of
      restriction, augmentation of the anterior mitral leaflet (AML) was achieved with
      a piece of autologous pericardium. METHODS: between January 1995 and December
      1999, out of 274 patients refered for rheumatic mitral disease, 143 patients
      underwent a repair (52%), 81% of them had pure regurgitation with no stenosis.
      Ring annuloplasty was performed in all cases. Two techniques used for treating
      the restrictive componant of the regurgitation were compared in two consecutive
      cohort of patients: no AML augmentation (n=62) and AML augmentation (n=81). Mean
      age was 42 + 3 years and all preoperative variables were comparable except for
      the incidence of redo patients who all underwent AML extension. RESULTS: in
      hospital mortality was 0.7% (n=1 with AML extension) and there was one early
      reoperation for a pericardial patch dehiscence. After a mean follow-up of 3.2
      years, there was one sudden death (no AML extension). The reoperation rate was
      lower with (2.5%) than without (12.9%) AML augmentation (p<0.05). Echographic
      study showed a lower incidence of recurrency of mitral insufficiency when AML
      augmentation had been performed (grade 2: 9% and grade 3: 3%) as compared to no
      AML augmentation (grade 2: 35% and grade 3: 14%) (p<0.05). The mitral orifice
      area was larger (AML augmentation: 2.2 + 0.3 cm2 vs no AML augmentation: 1.8 +
      0.4 cm2). CONCLUSION: ring annuloplasty alone failed to correct rheumatic mitral
      insufficiency in all cases. AML augmentation improved the quality of the repair
      and decreased the risk of reoperation.

PMID- 15521481
TI  - [Brain natriuretic peptide (BNP) and N-terminal-pro BNP in chronic haemodialysed
      renal failure].
AB  - Brain natiuretic peptide (BNP) and N-Terminal-pro BNP (NT-proBNP) are biological
      markers of left ventricular dysfunction. An increase of one of these peptides is
      commonly observed in patients with chronic renal failure (CRF) undergoing
      haemodialysis, in the absence of cardiac failure or acute myocardial ischaemia.
      The interpretation and clinical implications of this finding are not known. This
      is a problem because cardiovascular disease is the main cause of morbidity and
      mortality in patients undergoing haemodialysis. In these patients, left
      ventricular hypertrophy and left ventricular dysfunction were associated with
      increased mortality. A biological marker of left ventricular dysfunction enabling
      early identification of high risk patients would be very useful in this
      population. Chronic renal failure and haemodialysis do not explain increased
      levels of BNP and NT-proBNP. Expansion of extra-cellular volume causing
      myocardial stretching and increased left ventricular pressures is the principal
      cause of increased BNP and NT-proBNP in haemodialysis patients. The left
      ventricular hypertrophy and endothelial dysfunction in severe chronic renal
      failure, systolic and diastolic left ventricular dysfunction, the associated
      cardiac disease (usually ischaemic) also contribute to this increase. In view of
      the relationship with left ventricular hypertrophy, left ventricular dysfunction,
      ischaemic heart disease, BNP and NT-proBNP are predictive factors of total and/or
      cardiovascular mortality in asymptomatic haemodialysed patients. The BNP/NT
      proBNP value should allow identification of high risk asymptomatic haemodialysed
      patients who would benefit from aggressive evaluation of left ventricular
      hypertrophy and dysfunction and appropriate, targeted therapeutic intervention.

PMID- 15521482
TI  - Heart failure, platelet activation and inhibition of the renin-angiotensin
      aldosterone system.
AB  - Heart failure is a highly prevalent disease in aging western populations,
      associated with a substantially increased risk of thromboembolic events, not only
      in severe but even in mild to moderate stages. This can partly be attributed to
      concomitant atrial fibrillation, a well-known risk factor for stroke, as well as
      a "hypercoagulable state" including formation of intraventricular thrombi. Left
      ventricular dysfunction results in decreased cardiac output, pulmonary congestion
      and neurohumoral activation with marked stimulation of the renin-angiotensin
      aldosterone system. Besides its contribution to progressive left ventricular
      remodelling, activation of the renin-angiotensin-aldosterone system is enhanced
      in the development of vascular endothelial dysfunction in heart failure,
      resulting in decreased nitric oxide bioavailability. Nitric oxide, however,
      controls vascular tone and inhibits platelet activation. Enhanced platelet
      activation has recently been described in patients with heart failure in sinus
      rhythm. This article summarises the potential contribution to platelet activation
      of vascular endothelial dysfunction and reduced formation of the platelet
      inhibitor nitric oxide, which increase further the risk for thromboembolic events
      in heart failure. Beneficial modulation of cardiac remodelling, left ventricular
      function, neurohumoral activation, endothelial dysfunction and platelet
      activation can be achieved by inhibition of the renin-angiotensin-aldosterone
      system.

PMID- 15521483
TI  - Local endovascular treatment of aortic aneurysms. From operating theater to lab
      bench.
AB  - Current treatment of aortic abdominal aneurysms by conventional surgery or
      endoprosthesis is flawed by high post-operative mortality and unpredictable
      durability of haemodynamic exclusion, respectively. We have developed
      endovascular approaches with cell and gene transfer, aimed at controlling further
      diameter expansion in an animal model of already-developed aneurysms in rats.
      Preliminary results suggest that both cell and gene endovascular therapy can be
      used to control expansion of aneurysms generated by inflammation and proteolytic
      destruction of the aortic wall.

PMID- 15521484
TI  - Gender aspects in heart failure. Pathophysiology and medical therapy.
AB  - Gender differences in the syndrome of heart failure (HF) occur in etiology and
      pathophysiology and lead to differences in the clinical presentation and course
      of the syndrome. In addition, gender specific treatment responses and gender
      associated differences in the behavior of treating physicians are found.
      Hypertension and diabetes play a major role as causes of HF in women and both
      interact in their pathophysiology with the renin angiotensin system (RAS).
      Modulation of the RAS by estrogens explains specific differences between pre- and
      post-menopausal women and men. Myocardial growth processes and myocardial calcium
      handling are differentially regulated in female and male myocytes. Myocardial
      remodeling with age and as a consequence of mechanical load differs in women and
      men. For yet unknown reasons, HF with preserved systolic function seems to be
      more frequent in women than in men and the clinical course of systolic HF is
      different in both genders. Medical therapy in heart failure has usually not been
      specified according to gender and gender specific analysis has been neglected in
      most large survival trials. Only a post-hoc analysis of gender differences led to
      the recognition of increased mortality with digitalis therapy in women. Single
      studies on angiotensin converting enzyme inhibitors (ACEI) or beta-receptor
      blockers did not reach significant end points in women whereas meta-analyses
      showed overall positive effects. Side effects of ACEI are more common and
      pharmacokinetics of beta-blockers are different in women. Angiotensin receptor
      blockers (ARB) are equally well tolerated in women and men. RAS inhibition may be
      particularly advantageous in postmenopausal women in whom the natural modulation
      of the RAS by estrogens is lost.

PMID- 15521485
TI  - The microscopic transitional zone between elastic and muscular arteries.
AB  - The microscopic transitional zone (TZ) is a segment of the arterial tree, where
      elastic-type wall architecture is relayed by one of muscular type. Since arterial
      TZ's are often sites of atherosclerotic and non-atherosclerotic lesions, this
      histologic anatomic substrate should be considered in the etiology and
      pathogenesis of vascular diseases. Herein, the topography and fine structure of
      TZ in renal arteries and carotid bifurcation (tripod) is described, based on
      randomly collected human autopsy specimens. The average length of the TZ was
      found to be 10 mm in the renal arteries. The TZ In the carotid tripod was
      localised only in the postbifurcational segments, where the length varied between
      5 and more than 20 mm. In accordance with previous data from the literature, our
      results confirm a different ratio of scleroprotein components (elastin, collagen)
      and vascular smooth muscle cells (VSMC) in the microscopic TZ of arteries.
      Immunohistochemistry for lymphomonocytic antigens revealed no underlying
      inflammatory condition, especially no evidence of active cellular scavenging and
      an increased apoptotic rate of VSMC. We perceive the TZ as an arterial segment of
      reduced architectural compliance and, therefore, as a potential site of
      mechanotransductional failure leading to vascular diseases.

PMID- 15521486
TI  - [Recommendations on the implantation and surveillance of implantable
      defibrillators].

PMID- 15521487
TI  - [Pediatric mechanical circulatory assistance. Biventricular assistance for
      fulminant myocarditis in a 5 year old child].
AB  - The authors report the case of a 5 years old infant with cardiogenic shock due to
      a fulminant myocarditis. The severity of the shock which was refractory to
      conventional therapies necessitated to require to a cardiopulmonary bypass on
      emergency, followed by an external pneumatic bi-ventricular assistance. After 10
      days (3 days with cardioplumonary bypass and 7 days of bi-ventricular
      assistance), the patient had been able to be disconnected of any mechanical
      circulatory supply with total recovery of the cardiac function.

PMID- 15521488
TI  - [Right intracardiac thrombus in Behcet's disease].
AB  - The authors report the clinical history of a 22-year-old woman, followed for
      Behcet's disease, who presented a prolonged fever for two months associated with
      oral and genital ulcerations. There was an inflammatory syndrome, papillary
      oedema without brain injury. Echocardiography revealed moderate pericardial
      effusion and voluminous thrombosis of right atria and right ventricle. Chest
      computed tomography showed a lung infarction without thrombosis of pulmonary
      artery. The antiphospholipid antibodies were negatives. The treatment was based
      on corticotherapy and anticoagulation with a good outcome. In Behcet disease,
      cardiac involvement manifestations as pericardial, myocardial or endocardial
      lesions. This case underlines the rarity of cardiac thrombosis in Behcet disease.

PMID- 15521489
TI  - Effects of classifier structures and training regimes on integrated segmentation
      and recognition of handwritten numeral strings.
AB  - In integrated segmentation and recognition of character strings, the underlying
      classifier is trained to be resistant to noncharacters. We evaluate the
      performance of state-of-the-art pattern classifiers of this kind. First, we build
      a baseline numeral string recognition system with simple but effective
      presegmentation. The classification scores of the candidate patterns generated by
      presegmentation are combined to evaluate the segmentation paths and the optimal
      path is found using the beam search strategy. Three neural classifiers, two
      discriminative density models, and two support vector classifiers are evaluated.
      Each classifier has some variations depending on the training strategy: maximum
      likelihood, discriminative learning both with and without noncharacter samples.
      The string recognition performances are evaluated on the numeral string images of
      the NIST Special Database 19 and the zipcode images of the CEDAR CDROM-1. The
      results show that noncharacter training is crucial for neural classifiers and
      support vector classifiers, whereas, for the discriminative density models, the
      regularization of parameters is important. The string recognition results compare
      favorably to the best ones reported in the literature though we totally ignored
      the geometric context. The best results were obtained using a support vector
      classifier, but the neural classifiers and discriminative density models show
      better trade-off between accuracy and computational overhead.

PMID- 15521490
TI  - Convolutional face finder: a neural architecture for fast and robust face
      detection.
AB  - In this paper, we present a novel face detection approach based on a
      convolutional neural architecture, designed to robustly detect highly variable
      face patterns, rotated up to +/-20 degrees in image plane and turned up to +/-60
      degrees, in complex real world images. The proposed system automatically
      synthesizes simple problem-specific feature extractors from a training set of
      face and nonface patterns, without making any assumptions or using any hand-made
      design concerning the features to extract or the areas of the face pattern to
      analyze. The face detection procedure acts like a pipeline of simple convolution
      and subsampling modules that treat the raw input image as a whole. We therefore
      show that an efficient face detection system does not require any costly local
      preprocessing before classification of image areas. The proposed scheme provides
      very high detection rate with a particularly low level of false positives,
      demonstrated on difficult test sets, without requiring the use of multiple
      networks for handling difficult cases. We present extensive experimental results
      illustrating the efficiency of the proposed approach on difficult test sets and
      including an in-depth sensitivity analysis with respect to the degrees of
      variability of the face patterns.

PMID- 15521491
TI  - Hybrid genetic algorithms for feature selection.
AB  - This paper proposes a novel hybrid genetic algorithm for feature selection. Local
      search operations are devised and embedded in hybrid GAs to fine-tune the search.
      The operations are parameterized in terms of their fine-tuning power, and their
      effectiveness and timing requirements are analyzed and compared. The
      hybridization technique produces two desirable effects: a significant improvement
      in the final performance and the acquisition of subset-size control. The hybrid
      GAs showed better convergence properties compared to the classical GAs. A method
      of performing rigorous timing analysis was developed, in order to compare the
      timing requirement of the conventional and the proposed algorithms. Experiments
      performed with various standard data sets revealed that the proposed hybrid GA is
      superior to both a simple GA and sequential search algorithms.

PMID- 15521492
TI  - Image distortion analysis using polynomial series expansion.
AB  - In this paper, we derive a technique for analysis of local distortions which
      affect data in real-world applications. In the paper, we focus on image data,
      specifically handwritten characters. Given a reference image and a distorted copy
      of it, the method is able to efficiently determine the rotations, translations,
      scaling, and any other distortions that have been applied. Because the method is
      robust, it is also able to estimate distortions for two unrelated images, thus
      determining the distortions that would be required to cause the two images to
      resemble each other. The approach is based on a polynomial series expansion using
      matrix powers of linear transformation matrices. The technique has applications
      in pattern recognition in the presence of distortions.

PMID- 15521493
TI  - Statistical region merging.
AB  - This paper explores a statistical basis for a process often described in computer
      vision: image segmentation by region merging following a particular order in the
      choice of regions. We exhibit a particular blend of algorithmics and statistics
      whose segmentation error is, as we show, limited from both the qualitative and
      quantitative standpoints. This approach can be efficiently approximated in linear
      time/space, leading to a fast segmentation algorithm tailored to processing
      images described using most common numerical pixel attribute spaces. The
      conceptual simplicity of the approach makes it simple to modify and cope with
      hard noise corruption, handle occlusion, authorize the control of the
      segmentation scale, and process unconventional data such as spherical images.
      Experiments on gray-level and color images, obtained with a short readily
      available C-code, display the quality of the segmentations obtained.

PMID- 15521494
TI  - Robust adaptive-scale parametric model estimation for computer vision.
AB  - Robust model fitting essentially requires the application of two estimators. The
      first is an estimator for the values of the model parameters. The second is an
      estimator for the scale of the noise in the (inlier) data. Indeed, we propose two
      novel robust techniques: the Two-Step Scale estimator (TSSE) and the Adaptive
      Scale Sample Consensus (ASSC) estimator. TSSE applies nonparametric density
      estimation and density gradient estimation techniques, to robustly estimate the
      scale of the inliers. The ASSC estimator combines Random Sample Consensus
      (RANSAC) and TSSE: using a modified objective function that depends upon both the
      number of inliers and the corresponding scale. ASSC is very robust to
      discontinuous signals and data with multiple structures, being able to tolerate
      more than 80 percent outliers. The main advantage of ASSC over RANSAC is that
      prior knowledge about the scale of inliers is not needed. ASSC can simultaneously
      estimate the parameters of a model and the scale of the inliers belonging to that
      model. Experiments on synthetic data show that ASSC has better robustness to
      heavily corrupted data than Least Median Squares (LMedS), Residual Consensus
      (RESC), and Adaptive Least Kth order Squares (ALKS). We also apply ASSC to two
      fundamental computer vision tasks: range image segmentation and robust
      fundamental matrix estimation. Experiments show very promising results.

PMID- 15521495
TI  - Learning to detect objects in images via a sparse, part-based representation.
AB  - We study the problem of detecting objects in still, gray-scale images. Our
      primary focus is the development of a learning-based approach to the problem that
      makes use of a sparse, part-based representation. A vocabulary of distinctive
      object parts is automatically constructed from a set of sample images of the
      object class of interest; images are then represented using parts from this
      vocabulary, together with spatial relations observed among the parts. Based on
      this representation, a learning algorithm is used to automatically learn to
      detect instances of the object class in new images. The approach can be applied
      to any object with distinguishable parts in a relatively fixed spatial
      configuration; it is evaluated here on difficult sets of real-world images
      containing side views of cars, and is seen to successfully detect objects in
      varying conditions amidst background clutter and mild occlusion. In evaluating
      object detection approaches, several important methodological issues arise that
      have not been satisfactorily addressed in previous work. A secondary focus of
      this paper is to highlight these issues and to develop rigorous evaluation
      standards for the object detection problem. A critical evaluation of our approach
      under the proposed standards is presented.

PMID- 15521496
TI  - Effective multiresolution arc segmentation: algorithms and performance
      evaluation.
AB  - Arc segmentation plays an important role in the process of graphics recognition
      from scanned images. The GREC arc segmentation contest shows there is a lot of
      room for improvement in this area. This paper proposes a multiresolution arc
      segmentation method based on our previous seeded circular tracking algorithm
      which largely depends on the OOPSV model. The newly-introduced multiresolution
      paradigm can handle arcs/circles with large radii well. We describe new
      approaches for arc seed detection, arc localization, and arc verification, making
      the proposed method self-contained and more efficient. Moreover, this paper also
      brings major improvement to the dynamic adjustment algorithm of circular tracking
      to make it more robust. A systematic performance evaluation of the proposed
      method has been conducted using the third-party evaluation tool and test images
      obtained from the GREC arc segmentation contests. The overall performance over
      various arc angles, arc lengths, line thickness, noises, arc-arc intersections,
      and arc-line intersections has been measured. The experimental results and time
      complexity analyses on real scanned images are also reported and compared with
      other approaches. The evaluation result demonstrates the stable performance and
      the significant improvement on processing large arcs/circles of the MAS method.

PMID- 15521497
TI  - A flexible similarity measure for 3D shapes recognition.
AB  - This paper is devoted to presenting a new strategy for 3D objects recognition
      using a flexible similarity measure based on the recent Modeling Wave (MW)
      topology in spherical models. MW topology allows us to establish an n
      connectivity relationship in 3D objects modeling meshes. Using the complete
      object model, a study on considering different partial information of the model
      has been carried out to recognize an object. For this, we have introduced a new
      feature called Cone-Curvature (CC), which originates from the MW concept. CC
      gives an extended geometrical surroundings knowledge for every node of the mesh
      model and allows us to define a robust and adaptable similarity measure between
      objects for a specific model database. The defined similarity metric has been
      successfully tested in our lab using range data of a wide variety of 3D shapes.
      Finally, we show the applicability of our method presenting experimentation for
      recognition on noise and occlusion conditions in complex scenes.

PMID- 15521498
TI  - Depth estimation and image restoration using defocused stereo pairs.
AB  - We propose a method for estimating depth from images captured with a real
      aperture camera by fusing defocus and stereo cues. The idea is to use stereo
      based constraints in conjunction with defocusing to obtain improved estimates of
      depth over those of stereo or defocus alone. The depth map as well as the
      original image of the scene are modeled as Markov random fields with a smoothness
      prior, and their estimates are obtained by minimizing a suitable energy function
      using simulated annealing. The main advantage of the proposed method, despite
      being computationally less efficient than the standard stereo or DFD method, is
      simultaneous recovery of depth as well as space-variant restoration of the
      original focused image of the scene.

PMID- 15521499
TI  - A POCS-based graph matching algorithm.
AB  - A novel Projections Onto Convex Sets (POCS) graph matching algorithm is
      presented. Two-way assignment constraints are enforced without using elaborate
      penalty terms, graduated nonconvexity, or sophisticated annealing mechanisms to
      escape from poor local minima. Results indicate that the presented algorithm is
      robust and compares favorably to other well-known algorithms.

PMID- 15521500
TI  - Contour-based object tracking with occlusion handling in video acquired using
      mobile cameras.
AB  - We propose a tracking method which tracks the complete object regions, adapts to
      changing visual features, and handles occlusions. Tracking is achieved by
      evolving the contour from frame to frame by minimizing some energy functional
      evaluated in the contour vicinity defined by a band. Our approach has two major
      components related to the visual features and the object shape. Visual features
      (color, texture) are modeled by semiparametric models and are fused using
      independent opinion polling. Shape priors consist of shape level sets and are
      used to recover the missing object regions during occlusion. We demonstrate the
      performance of our method on real sequences with and without object occlusions.

PMID- 15521501
TI  - Debate over keeping complete, accurate inventory records.

PMID- 15521502
TI  - Hospitals honored for innovations in patient safety efforts.

PMID- 15521503
TI  - Reaching out to rural practices.

PMID- 15521504
TI  - How standards evolve and why they matter.

PMID- 15521505
TI  - Development and implementation ... how proposed changes become JCAHO standards.

PMID- 15521506
TI  - Communicating with a boss ... straight talk that won't get you fired.

PMID- 15521507
TI  - Meeting in-house needs with outside assets.

PMID- 15521508
TI  - Nuclear imaging: SPECT and PET scanners.

PMID- 15521509
TI  - Maintaining non-medical grade equipment in a patient environment.

PMID- 15521510
TI  - Network firewall basics--Part 1.

PMID- 15521511
TI  - Preventive maintenance: catching up and doing it right.

PMID- 15521512
TI  - How to do your part to attract more professionals to the field.

PMID- 15521513
TI  - Keeping active: how to apply for retired and emeritus status.

PMID- 15521514
TI  - Process validation: achieving the Operational Qualification phase.
AB  - The OQ phase of process validation is very important and is where the complete
      understanding of the process is determined by experimentation. This understanding
      is useful to: * establish optimal process parameters * understand variation that
      affect the process * aid in investigating process deviations. OQ is an important
      part of the entire process validation activity and essential to understanding a
      manufacturing process. The benefits of completing the OQ and overall process
      validation are the reasons that it makes business sense and receive the long-term
      benefits of producing high quality product and achieving customer satisfaction.

PMID- 15521515
TI  - Why it is not sufficient to study errors and incidents: human factors and safety
      in medical systems.

PMID- 15521516
TI  - Protecting and securing networked medical devices.
AB  - Designing, building, and maintaining a secure environment for medical devices is
      a critical component in health care technology management. This article will
      address several avenues to harden a health care information network to provide a
      secure enclave for medical devices.

PMID- 15521517
TI  - Electroporators based on digital formation of arbitrarily-shaped electroporation
      pulses.

PMID- 15521518
TI  - Challenges of JCAHO's new patient safety goals.

PMID- 15521519
TI  - [Factors involved in the onset of a dengue epidemic].

PMID- 15521520
TI  - Detection of antibodies to West Nile and Saint Louis encephalitis viruses in
      horses.

PMID- 15521521
TI  - [The right to health care: a component of full citizenship].

PMID- 15521522
TI  - [The influence of life events and social support in a psycho-educational
      intervention for women with depression].
AB  - OBJECTIVE: To investigate the influence of social support and adverse life events
      on depression symptoms, before and after therapy (15-30 days) and during follow
      up (4 months) of a psycho-educational intervention for depression. MATERIAL AND
      METHODS: The study population consisted of 254 women with depression symptoms
      selected among those seeking treatment for their symptoms in three community
      mental health centers and in one Ministry of Health center, all of them in Mexico
      City, between January 1998 and December 2000. The intervention has been proved
      effective previously in reducing depression symptoms. Symptoms were assessed
      using Radloff's CES-D scale, while specifically designed scales were used for
      events and social support. Hierarchical regression analyses were carried out to
      test various models. RESULTS: Model I: effect of variables: life events, social
      support, and socio-demographic variables (age, education level, income, and work
      status) on CES-D pre-treatment. The model was significant (p<0.000) and the first
      two variables and age were included in the model. Model 2: effect of the same
      predictive variables on CES-D post-treatment. The model was significant (p<0.001)
      and included social support and life events. Model 3: effect of the same
      variables on CES-D during follow-up. The model was significant (p<0.000) and
      included life events and educational achievement. Model 4: effect of social
      support and life events during follow-up on CES-D during follow-up. The model was
      also significant (p<0.000) and both variables were included in the model.
      Additional analyses for models 2 and 3 adding CES-D pre-treatment as a predictor
      showed that only the latter was significant. CONCLUSIONS: Life events and social
      support are associated with initial depression symptoms and also predict the
      reduction of symptoms following the psycho-educational intervention. This may be
      due to the high correlation of life events and social support with CES-D pre
      treatment. Life events and social support following the intervention also have an
      effect on CES-D in this same stage. The English version of this paper is
      available at: http://www.insp.mx/salud/index.html.

PMID- 15521523
TI  - [National health policies and local decisions in Mexico: the case of an
      intercultural hospital in Cuetzalan, Puebla].
AB  - OBJECTIVE: To identify the changes brought about by various national and
      international factors in an intercultural hospital of the municipality of
      Cuetzalan, Puebla. MATERIAL AND METHODS: A case study was conducted during 2000
      and 2001 in two Intercultural Hospitals of Mexico; the Cuetzalan Hospital in
      Puebla and the Jesus Maria Hospital in Nayarit State. Data were collected by
      means of 72 semi-structured interviews with allopathic therapists, indigenous
      therapists, and authorities of the different health care levels. Moreover,
      documental research was carried out on national policies for indigenous peoples
      as well as on indigenist policies. These policies were related with the five
      organizational stages of the hospital. State authorities gave their permission
      and interviewees signed informed consent. RESULTS: The hospital was created in
      1958 by the Ministry of Health as a biomedical institution, in agreement with the
      integrationist indigenist policies going on at the time. It remained so during
      the beginning of the administration by the National Indigenist Institute. In
      1990, the new participative indigenist policy trends and the creativity and
      sensitivity of some authorities, under the influence of international strategies,
      helped to transform the hospital into an Intercultural Hospital (offering both
      types of medicine, indigenous and allopathic) with regional coverage. In 2000,
      the devolution of the hospital to the State Ministry of Health, based on
      financial rather than socio-cultural considerations, caused the temporary loss of
      its intercultural character. The last stage as an Integral Hospital with
      Traditional Medicine (from 2003 onwards) was due to a combination of state
      official initiatives and the new political stance acquired by the Mexican
      indigenous movement. The hospital is now part of a regional project of five such
      hospitals officially denominated Integral Hospitals with Traditional Medicine, to
      be financed by the Puebla-Panama Plan of regional development. CONCLUSIONS: Our
      results confirmed that health organizations follow a historical process in which
      selected national and international forces open opportunities to promote
      intercultural health models that respond to the needs of indigenous populations.
      Despite the formerly held belief that traditional and scientific medicines were
      incompatible, this study demonstrates the viability of intercultural health care
      models that may become a real possibility in the country, based on new
      conventions to establish alternative and intercultural health services, thereby
      setting an example for other regions and countries. The English version of this
      paper is available at: http://www.insp.mx/salud/index.html.

PMID- 15521524
TI  - [Equity and fairness in the Mexican health system reform].
AB  - OBJECTIVE: To assess the equity and fairness of the Mexican health system reform
      that occurred in the late 1990's. MATERIAL AND METHODS: The Mexican reform
      process was evaluated using the benchmark-system designed by Daniels et al. This
      benchmark system was adapted to the Mexican setting by adding specific
      indicators. A documentary review of the Mexican reform process was conducted to
      score its performance for each benchmark. RESULTS: Except for housing and
      nutrition components, the reform included few actions related to health
      determinants. For health care, the main reform initiatives were those related to
      extending the coverage of essential health services and decentralizing health
      care provision to the states. Reform initiatives included few activities related
      to fair financing, tiering, emphasis on second and third level care,
      accountability, and transparency. CONCLUSIONS: The late nineties reform of the
      Mexican health system had some positive effect on access of the poor to health
      care and administrative efficiency, but little impact on fair financing, quality
      of care, and democratic governance. The English version of this paper is
      available at: http://www.insp.mx/salud/index.html.

PMID- 15521526
TI  - [Effects of some chemical and physical agents on the metacestode Taenia solium in
      spicy meat and sausage].
AB  - OBJECTIVE: To assess the effect of different cooking times and temperatures, as
      well as of some seasonings, on the viability of Taenia solium metacestodes in
      spicy meat and hot sausage. MATERIAL AND METHODS: This study was conducted by the
      Universidad Autonoma de Guerrero (Guerrero State Autonomous University), Mexico
      in 1999. Infected pork meat was bought in the community of Azacoaloya, in the
      municipality of Chilapa de Alvarez, Guerrero State. It was used to prepare spicy
      meat (adobada) and hot sausage (chorizo). Only the meat in which metacestode
      viability was proven was used. The products obtained underwent a) room
      temperature for 12 to 100 hours; b) temperatures of -10 to 37 degrees C for 24
      hours; c) boiling (97 degrees C) from 1 to 15 minutes. To determine the effect of
      the seasonings, batches were prepared using twice the amount of a specific
      seasoning. Trials were done and assessed three times. Proportion differences were
      established using the chi-squared test. RESULTS: At room temperature the lowest
      evagination occurred after 100 hours for both products (p<0.05). After 24 hours,
      the lowest evagination occurred at -10 degrees C in spicy meat and at 37 degrees
      C in hot sausage (p<0.05). At boiling temperature there was no evagination after
      10 minutes (p<0.05). In spicy meat, adding salt caused the most significant
      reduction; in hot sausage, thyme caused the most significant reduction (p<0.05).
      CONCLUSIONS: Meat with metacestodes should not be eaten, yet, it is being sold
      and used to prepare spicy meats. Adding spices can hide the metacestode, thus,
      adequate cooking of these meat products is necessary. These meats may be consumed
      at least four days after its preparation and spicy meat after a minimum of four
      days of refrigeration. The English version of this paper is available at:
      http://www.insp.mx/salud/index.html.

PMID- 15521525
TI  - [Early onset depression: prevalence, course, and treatment seeking delay].
AB  - OBJECTIVE: To estimate the prevalence of early onset depression in the Mexican
      population and compare its natural history, comorbidity and treatment latency
      between early onset and adult onset depression. MATERIAL AND METHODS: The
      National Survey of Psychiatric Epidemiology (ENEP) is representative of the
      Mexican urban population aged 18 to 65. The diagnostic instrument is the
      Composite International Diagnostic Interview (CIDI). Statistical analysis was
      performed with descriptive and logistic regression analyses, considering the
      multistage, stratified and weighted sample design of the survey. RESULTS: Two
      percent of the Mexican population has suffered from depression as children or
      adolescents, with an average 7 episodes during their lifetime (compared with 3
      episodes for adult onset); the first episode lasted a mean of 31 months (compared
      with 16 for adult onset) and generally did not receive any treatment.
      CONCLUSIONS: The longer duration of the first episode and the greater number of
      lifetime episodes for subjects with early onset is attributed to the lack of
      early detection and of timely treatment of depression in Mexican youth. The
      English version of this paper is available at:
      http://www.insp.mx/salud/index.html.

PMID- 15521527
TI  - [Evaluation of a screening method for Chagas disease in San Luis, Argentina].
AB  - Chagas disease is an endemic public health problem in the Province of San Luis,
      Argentina. The objective of this work was to evaluate the application of a
      screening method, focusing on the biochemical processing of capillary samples and
      diagnostic testing. MATERIAL AND METHODS: In the year 2002, samples of capillary
      blood were collected from 250 children in their homes; the samples were placed in
      glycerin buffer and processed by quantitative PHA and ELISA. The results were
      compared with venous blood samples from the same children, that were analyzed
      using the same assays, as well as by IFA, the standard method. RESULTS: The
      sensitivity, specificity, and positive and negative predictive values were 98.03,
      92.96, 78.12, and 99.46%, respectively. CONCLUSIONS: The serological assays PHA
      and ELISA conducted simultaneously were sufficiently sensitive and specific, thus
      validating the screening method. The method was easy to implement, had a low
      cost, and was well accepted by the selected population. The English version of
      this paper is available at: http://www.insp.mx/salud/index.html.

PMID- 15521528
TI  - [Meningococcal disease caused by Neisseria meningitidis: epidemiological,
      clinical, and preventive perspectives].
AB  - Bacterial meningitis constitutes a significant global public health problem. In
      particular, Neisseria meningitidis continues to be a public health problem among
      human populations in both developed and developing countries. Meningococcal
      infection is present as an endemic and an epidemic disease. Meningococcal disease
      is manifested not only as meningitis, but also as meningococcemia. The latter is
      usually fulminant. The global persistence of N. meningitidis is due to the
      significant number of carriers and the dynamics of transmission and disease.
      Approximately 500 million people worldwide are carriers of the bacterium in their
      nasopharynx. Multiple factors have been identified that predispose to the
      transmissibility of N. meningitidis, including active or passive inhalation
      tobacco smoking, upper viral respiratory tract infections, drought seasons, and
      overcrowding. These factors explain the frequent occurrence of outbreaks in
      military barracks, schools, prisons, and dormitories. Some of the determinants of
      invasiveness of the bacteria include nasopharyngeal mucosal damage in colonized
      individuals, virulence of the strains, absence of bactericidal antibodies, and
      deficiencies of the complement system. During both endemic and epidemic scenarios
      of meningococcal disease, control measures should include treating the cases with
      appropriate antimicrobial therapy (penicillin, ceftriaxone, or chloramphenicol);
      providing chemoprophylactic drugs to contacts (rifampin or ciprofloxacin), and
      close observation of contacts. Nevertheless, the key to effective control and
      prevention of meningococcal disease is immunoprophylaxis. Available vaccines
      include the polysaccharide monovalent, bivalent (serogroups A, C), or tetravalent
      (A, C, Y, W-135 serogroups) vaccines; conjugate vaccine (serogroup C); and the
      combined vaccine with outer membrane proteins and polysaccharide (serogroups B,
      C). Due to a recent increase in case reporting of serogroup C N. meningitidis in
      Mexico, we have developed a national response strategy that includes availability
      of vaccines and medications for chemoprophylaxis. This review aims at providing
      health care workers with updated information regarding the epidemiological,
      clinical, and preventive aspects of meningococcal disease. The English version of
      this paper is available at: http://www.insp.mx/salud/index.html.

PMID- 15521529
TI  - [The role of epidemiology in mental disorder research].
AB  - Mental disorders, including substance abuse, are part of the Mexican
      epidemiologic scenario and will remain so during several decades. They may even
      become more prominent as causes of disease, disability, and death in our country.
      It is thus imperative to frame appropriate management strategies to curb these
      problems without delay. This paper aims at outlining epidemiology of mental
      diseases as a field of study, and to identify its limitations. Emphasis is made
      on common elements shared with other more traditional fields of epidemiology, as
      well as on the specific contributions made by this particular field to
      epidemiology and to psychiatry in general. This paper describes the main study
      designs and problems in this field of epidemiology, its usefulness in prevention
      actions, and future challenges. A unique characteristic of mental disorder
      epidemiology is that its target diseases manifest in two levels: behaviorally
      (for example, compulsive hand-washing) and as an element of the individual's
      mental life (e.g., obsession with bacteria being a constant, omnipresent health
      threat). It follows that much of the knowledge currently available on the
      phenomena of mental disorders in general is based on the self-reported insight of
      individuals. Trained clinicians have collected such reports by interview or with
      standardized questionnaires. This field of epidemiology is characterized by
      having two-sides: a mental disorder is a problem in and of itself, causing
      suffering and prompting the search for specialized care, as it has peculiar
      clinical manifestations. On the other hand, mental disorder epidemiology also
      focuses on determining factors (drug use, abuse, or addiction) and on the way
      these independent variables result in certain processes and outcomes (such as
      accidents, homicide, suicide, liver cirrhosis, etc.). Finally, the epidemiology
      of mental disorders has also been set apart by its focus in series of processes
      that are not suitably classified as syndromes, but which are germane to public
      health, for example, violence. The epidemiology of mental disorders faces great
      challenges in the new millennium, including a complex, changing epidemiologic
      scenario. Several important issues will influence the future development of
      mental disorder epidemiology: measurement of mental disorders and risk factors,
      more efficient sampling design and methods, the relationships among biological
      research, genetics, social studies, and epidemiology, and the interface between
      epidemiology and the evaluation of therapies and health services.

PMID- 15521530
TI  - [Hospital discharge statistics from public hospital of the National Health
      System, 2003].

PMID- 15521531
TI  - [West Nile fever: an emerging disease in Mexico].

PMID- 15521532
TI  - [Forty-five million Americans have no health insurance].

PMID- 15521533
TI  - [Serious deterioration of the Chinese people's health].

PMID- 15521534
TI  - The Jim interview.

PMID- 15521535
TI  - Bristol-Myers Squibb announces awards.

PMID- 15521536
TI  - New ethics rules at NIH.

PMID- 15521537
TI  - HHS will lead government-wide effort to enhance biosecurity.

PMID- 15521538
TI  - National Eye Institute recognizes Wurtz for outstanding Brain/Eye Institute.

PMID- 15521539
TI  - Scientists find HIV-blocking protein in monkeys.

PMID- 15521540
TI  - South Korean researchers announce successful harvesting of stem cells from cloned
      human embryos; United States behind.

PMID- 15521541
TI  - Salaries at NIH draw congressional scrutiny.

PMID- 15521542
TI  - Gene variants may increase susceptibility to type 2 diabetes.

PMID- 15521543
TI  - Issues in developing the medical scientist: introduction to the series.

PMID- 15521544
TI  - Issues in developing the medical scientist, part 1: interview with Dr. Robert W.
      Schrier, MD.

PMID- 15521545
TI  - The National Institutes of Health roadmap and the developing world.

PMID- 15521547
TI  - "Keeping the balance": life and time as a clinical researcher.

PMID- 15521546
TI  - Statin therapy for cardiac hypertrophy and heart failure.
AB  - Cardiac hypertrophy leading to heart failure is a major cause 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 guanosine
      triphosphatase family, such as Rac1 and RhoA. Because Rac1 is a requisite
      component of reduced nicotinamide adenine dinucleotide phosphate 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 up-regulation of
      endothelial nitric oxide synthase in the endothelium and the heart. This results
      in increased angiogenesis and myocardial perfusion, decreased myocardial
      apoptosis, and improvement in endothelial and cardiac function. Because these
      effects of statins occur independently of cholesterol lowering, statins may have
      therapeutic benefits in nonhyperlipidemic patients with cardiac hypertrophy and
      heart failure.

PMID- 15521548
TI  - Finding balance in a life in clinical research: it's about time.

PMID- 15521549
TI  - Time management in academic medicine.

PMID- 15521551
TI  - A timeless personality--a delightful memory.

PMID- 15521550
TI  - Time management top 10 list.

PMID- 15521552
TI  - Remembering Sir Bernard Katz (1911--2003).

PMID- 15521555
TI  - Short-term physical training alters cardiovascular autonomic response amplitude
      and latencies.
AB  - This study reports the results of 15 days of exercise training in 25 adult males
      on cardiovascular autonomic response amplitude and latencies. A standard battery
      of autonomic function tests including both activity (tone) and reactivity was
      used. Parasympathetic activity as evaluated from Heart rate variability (HRV)
      showed no statistically significant change in both time and frequency domain
      measures, similarly Sympathetic activity as measured by QT/QS2 ratio showed no
      statistically significant change, but there was a trend of a decrease in
      sympathetic activity and an increase in parasympathetic activity. There were no
      changes in the parameters measuring parasympathetic reactivity. Sympathetic
      reactivity as evaluated by diastolic blood pressure responses to hand grip test
      (HGT) and cold pressor test (CPT) showed significant decreases. Time domain
      assessment of autonomic responses was done by measuring tachycardia and
      bradycardia latencies during Valsalva maneuver (VM) and lying to standing test
      (LST). Physical training resulted in a decrease in tachycardia latency during LST
      and a decrease in bradycardia latency during VM. We conclude from the present
      study that 15 days of physical training is not enough to alter autonomic activity
      and PNS reactivity but can result in changes in SNS reactivity and latency
      parameters. We hypothesize that a decrease in bradycardia latency during VM
      signifies a faster recovery of heart rate during VM and a decrease in tachycardia
      latency during LST denotes a delayed activation of the system both of which are
      favorable cardiovascular responses.

PMID- 15521553
TI  - Why the medial preoptic area is important for sleep regulation.
AB  - The medial preoptic area (mPOA) is one of the many areas in the brain that
      control sleep. Apart from sleep, the mPOA is important for the regulation of body
      temperature, and other important body functions aimed at energy homeostasis. In
      sleep regulation, the major function of this area is to maintain sleep. Though
      the mPOA controls sleep and body temperature through independent neuronal
      circuits, it is essential for organising the sleep architecture, as per the
      thermoregulatory requirement. The functional integrity of the mPOA may be
      essential for the regulation of energy homeostasis, in response to alterations in
      the ambient temperature, heat producing physical activity and sleep-wakefulness.
      Thus, the mPOA forms part of the brain that integrates regulations aimed at
      preservation of self. The mPOA is important for maintaining the "set point" for
      not only body temperature, but it is also important for maintaining the "set
      point" for several physiological parameters including sleep-wakefulness.

PMID- 15521554
TI  - Persistent/delayed toxic effects of low-dose sarin and pyridostigmine under
      physical stress (exercise) in mice.
AB  - Pyridostigmine bromide, a reversible anticholinesterase drug, was used by
      military personnel during the Gulf War. They were under physical stress and might
      have been exposed to low-dose nerve gas, sarin. This study examined the
      interactions of low-dose sarin and pyridostigmine in exercised mice. Male NIH
      Swiss mice were treated as follows: 1) Control; 2) Sarin (0.01 mg/kg, sc); 3)
      exercise; 4) sarin plus exercise; 5) pyridostigmine; 6) pyridostigmine plus
      exercise; 7) pyridostigmine plus sarin; 8) pyridostigmine plus sarin plus
      exercise. Exercise was given daily for 10 weeks on treadmill and pyridostigmine
      and sarin were administered daily during the 5th and 6th weeks only. Respiratory
      exchange ratio decreased significantly during the dosing period of 5th and 6th
      weeks in groups 4, 6, and 8. Animals were sacrificed 24 hours after the ten-week
      exercise, tissues isolated and analyzed. Sarin significantly decreased
      butyrylcholine esterase (BChE) activity in plasma; AChE activity in platelet,
      triceps muscle, and striatum; neurotoxic esterase (NTE) activity in platelets,
      spinal cord, cortex and striatum and malondialdehyde (MDA) levels in sciatic
      nerve and cord. Sarin plus exercise significantly reduced BChE activity in
      plasma; acetylcholinesterase (AChE) activity in platelets, muscle, nerve and
      striatum; NTE activity in platelets, cord, cortex and striatum; and increased
      creatinine phosphokinase (CK) activity in plasma and MDA levels in cord.
      Pyridostigmine plus exercise significantly decrease BChE activity in plasma; AChE
      activity in muscle and enhanced malondialdehyde (MDA) levels in muscle.
      Pyridostigmine plus sarin significantly decreased NTE activity in platelets,
      cord, cortex and striatum. Pyridostigmine plus sarin plus exercise significantly
      altered AChE activity and MDA levels in muscle; and NTE activity in platelets,
      nerve, cord and cortex. Exercise significantly augmented the changes in plasma CK
      activity, muscle and nerve AChE activity, platelet NTE activity and cord MDA
      levels induced by sarin. It is concluded that physical stress (exercise) enhanced
      the persistent/delayed toxic effects of low-dose sarin and pyridostigmine in
      specific tissues of mice.

PMID- 15521556
TI  - Effect of prenatal species-specific and music stimulation on the postnatal
      auditory preference of domestic chick.
AB  - Perinatal sensory experience plays an important role in the development of
      perceptual preferences. In the present study prenatal enrichment with sound
      stimulus was given to see its effect on the development of postnatal auditory
      preference. Auditory stimulation with either species-specific (chicken maternal
      and hatching calls) or music (slow and fast sitar music) sounds was provided to
      two separate sets of fertilized eggs from the day 10 of incubation. The postnatal
      auditory preference of the chicks to either species-specific or music sounds was
      then tested at different time periods after hatching. All the chicks,
      irrespective of the type of prenatal exposure, showed preference for species
      specific maternal calls. Notably, the music stimulated chicks did not show
      preference for either slow or fast music. In both the experimental groups, the
      number of chicks responding to the species-specific maternal calls was
      significantly (P<0.001) more at 24 h and 48 h post hatch, when compared with the
      unstimulated control group. Comparison of the species-specific stimulated group
      with the music stimulated group, for auditory preference to the maternal calls,
      did not show any significant difference. Further, in the species-specific sound
      stimulated groups, there was a significant (P<0.001) increase in the number of
      chicks responding to maternal calls at 60 h of age with repeated testing.
      However, there was no effect of peer imprinting on the auditory preference of the
      chicks, in both the experimental groups. The results indicate that prenatal
      auditory experience with either species-specific or non-specific music enhances
      the postnatal auditory preference of chicks for the species-specific sounds.

PMID- 15521557
TI  - Energy cost and cardiorespiratory changes during the practice of Surya Namaskar.
AB  - Surya Namaskar (SN), a group of Yogic exercise consists of a set of twelve
      postures which is practiced by some of the yoga practitioners. The present study
      was undertaken to observe critically the energy cost and different
      cardiorespiratory changes during the practice of SN. Twenty-one male volunteers
      from the Indian Army practiced selected Yogic exercises for six days in a week
      for three months duration. The Yogic practice schedule consisted of Hatha Yogic
      Asanas (28 min), Pranayama (10.5 min) and Meditation (5 min). In the Yogic
      practice schedule 1st they practiced Kapal Bhathi (breathing maneuvers) for 2 min
      then Yogamudra (yogic postural exercise) for 2 min, after that they took rest
      until oxygen consumption and heart rate (HR) came to resting value. Subsequently
      subjects performed SN for 3 min 40 seconds on an average. After three months of
      training at the beginning of the fourth month subjects performed entire Yogic
      practice schedule in the laboratory as they practiced during their training
      session and experiments were carried out. Their pulmonary ventilation,
      carbondioxide output, Oxygen consumption, HR and other cardiorespiratory
      parameters were measured during the actual practice of SN. Oxygen consumption was
      highest in the eighth posture (1.22+/-0.073 1 min(-1)) and lowest in the first
      posture (0.35+/-0.02 1 min(-1)). Total energy cost throughout the practice of SN
      was 13.91 kcal and at an average of 3.79 kcal/min. During its practice highest HR
      was 101+/-13.5 b.p.m. As an aerobic exercise SN seemed to be ideal as it involves
      both static stretching and slow dynamic component of exercise with optimal stress
      on the cardiorespiratory system.

PMID- 15521558
TI  - The effect of L-arginine on the memory impairing action of phenobarbitone in rats
      that convulsed after the injection of picrotoxin.
AB  - Nitric oxide (NO) has been demonstrated to enhance memory formation in
      experimental animals. However, the effect of NO precursor, L-arginine has never
      been tested on the memory impairing action of the aniepileptic drug,
      phenobarbitone independently and concurrently with the convulsant, picrotoxin
      (PCT). In view of this, in the present study, rats that acquired the shock
      avoidance task were treated with PCT (5 mg/ kg). Twenty four h later these
      animals were injected with L-arginine (500, 1000 mg/kg) and phenobarbitone (10,
      20 mg/kg). Retention of the acquired task was tested 30 min later. The effect of
      these compounds were correlated with the changes produced by them on the
      concentration of NO in the brain. PCT and phenobarbitone (20 mg/kg) inhibited
      memory process independently and concurrently. NO concentration was not altered
      by phenobarbitone but was decreased in PCT-treated animals. L-arginine (1000
      mg/kg) increased the concentration of NO in PCT and phenobarbitone treated
      animals and prevented these compounds from impairing memory process independently
      and concurrently. These results lead to a conclusion that L-arginine may be used
      in combination with phenobarbitone to prevent both the cognitive side effect of
      the antiepileptic drug and the impairment of memory that is associated with the
      convulsion disorder.

PMID- 15521559
TI  - Lipid peroxidation, hemolysis and antioxidant enzymes of erythrocytes in stroke.
AB  - Erythrocyte membrane lipid peroxidation and consequent percentage hemolysis and
      related antioxidant enzymes viz., superoxide dismutase, glutathione peroxidase,
      glutathione reductase and catalase were determined in 16 cases of hemorrhagic
      stroke and 30 cases of thrombotic stroke. The results obtained were compared with
      50 age and sex matched controls. 12 thrombotic stroke patients who showed
      symptomatic recovery after medication were considered for follow up. Lipid
      peroxidation and percentage hemolysis in patients with thrombotic stroke and
      hemorrhagic stroke was significantly elevated when compared to controls.
      Glutathione reductase and superoxide dismutase levels were found to be
      significantly reduced in thrombotic stroke and hemorrhagic stroke respectively,
      when compared to healthy subjects. There was no significant difference in the
      other parameters when compared to controls. In post treatment thrombotic stoke,
      catalase and glutathione reductase levels increased significantly and oxidative
      hemolysis decreased compared to their pretreatment values. Thus, our results
      indicate considerable oxidative stress in stroke.

PMID- 15521560
TI  - Lysosomal enzyme activity during development of carbon tetrachloride induced
      cirrhosis in rats.
AB  - The present study was undertaken to determine whether there is any alteration in
      the activities of lysosomal enzymes in the liver and sera of rats during the
      course of carbon tetrachloride (CCl4) induced cirrhosis in rats. Cirrhosis was
      induced by the chronic administration of carbon tetrachloride plus
      phenobarbitone. N-acetyl glucosaminidase, P-glucuronidase and acid phosphatase
      were assayed spectrophotometrically in the liver homogenates and in the sera at
      different stages of liver injury i.e., necrosis, fibrosis, and cirrhosis.
      Significant increase in the "basal" activities of N acetyl glucosaminidase, beta
      glucuronidase, and acid phosphatase were observed in the livers of rats during
      the course of development of cirrhosis. As the liver injury progressed from
      necrosis to cirrhosis, the 'free' activities of these three enzymes also
      increased. The 'total' activities of the enzymes studied were either decreased or
      remained unaltered. The increased 'free' activities of the lysosomal enzymes in
      the liver of CCl4 treated rats may contribute to cellular autophagy and tissue
      catabolism, which may subsequently lead to cirrhosis.

PMID- 15521561
TI  - Tilt table testing in the diagnostic evaluation of presyncope and syncope: a case
      series report.
AB  - Tilt table testing has long been used as a standard tool in the diagnostic
      evaluation of syncope. However, differences of opinion exist with regard to its
      utility in the evaluation of patients with only presyncopal attacks. We present
      the results of drug-free, 70-degree head-up tilt table tests (maximum duration of
      45 minutes), conducted between May 2002 and May 2003 in the Department of
      Physiology at JIPMER. This series consisted of both male and female patients (age
      6-79 yr) with presyncope (n = 43), unexplained syncope (n = 43) and asymptomatic
      healthy volunteers without a history of syncope (n = 14). 28 out of 43 patients
      with unexplained syncope had a history of recurrent syncope while the remaining
      15 had only 1 episode. 2 out of 43 patients (4.6%) with a history of only
      presyncopal attacks had a positive test (induction of intense presyncope and/or
      syncope accompanied by hypotension and/or a relative bradycardia). 21 out of 43
      patients (49%) with a history of syncope had a positive test. 7 had vasodepressor
      syncope due to hypotension, 6 had cardioinhibitory syncope characterized by
      asystole and 10 had a mixed form of the vasovagal syndrome characterized by
      hypotension as well as bradycardia. 18 out of 28 patients (64%) with recurrent
      unexplained syncope had a positive test. All fourteen healthy volunteers had a
      negative test. We conclude that tilt table testing is useful in the diagnostic
      evaluation of patients with unexplained syncope, especially those with recurrent
      syncope, but not in the evaluation of patients with presyncope alone.

PMID- 15521562
TI  - Iodine nutritional status of school children in a rural area of Howrah district
      in the Gangetic West Bengal.
AB  - The objective of the study was to assess the status of iodine nutrition in an
      area of Howrah district where iodine deficiency disorders (IDD) were reported
      despite the introduction of iodised salt for general use. A total of 969 school
      children in the age group 6-12 years of both sexes were clinically examined for
      goitre. On the spot 242 urine samples were collected from the children to study
      the iodine and thiocyanate excretion pattern and 108 edible salt samples were
      collected from the homes of the children to measure iodine level. Drinking water
      samples were collected to evaluate the bioavailability of iodine in the region.
      The total goitre prevalence was 37.6% (Grade 1: 32.6%; Grade 2: 4.9%). The median
      urinary iodine level was 35 microg/dL, 12.5% urine samples had iodine level below
      10 microg/dL and no sample was found to contain iodine below 5 microg/dL. In
      51.9% salt samples iodine level was below 15 ppm and the iodine level in the
      drinking water was about 82 microg/L. The people of the area consume foods from
      the vegetables of the Brassica family and mean thiocyanate level was 0.747+/-0.21
      mg/dL. The-findings of the present study indicated that as per clinical criteria
      of WHO/UNICEF/ICCIDD, IDD is a severe public health problem though apparently
      there is no biochemical iodine deficiency. Overall results indicate that factors
      other than iodine deficiency may have a role in the persistence of endemic goitre
      in the post salt-iodisation in this region.

PMID- 15521563
TI  - Non-secretor status; a predisposing factor for vaginal candidiasis.
AB  - A secretor is an individual who secretes blood group antigens into body fluids
      such as saliva, sweat, tears, semen and serum. An attempt has been made to
      establish the correlation between the secretor status and susceptibility to
      vaginal candidiasis. The secretor status was determined by haemagglutination
      inhibition technique. The presence of Candida albicans infection was detected by
      direct microscopy of the wet smear and confirmed by germ tube test and corn meal
      agar test. It was observed that out of the 64 patients, 15 were secretors and 49
      were non-secretors. However 43 subjects were secretors and 13 non-secretors among
      the 56 controls. Thus prevalence of vaginal candidiasis was significantly higher
      in non-secretor group (P<0.01). The absence of blood group antigens in the body
      fluids and the lack of enzyme glycosyl transferase enhance the attachment of
      yeast to the epithelial cell and render the non-secretor more prone to infection.

PMID- 15521564
TI  - Effect of high altitude on human auditory brainstem responses.
AB  - The effect of hypobaric hypoxia on Brain Stem Auditory evoked potentials (BAERs)
      were studied. BAERs were recorded in 30 volunteers at sea level (SL) and then at
      high altitude (HA) of 3200 m (HA I) and 4300 m (HA II) in Eastern Himalayas and
      on return to sea level (RSL). The BAERs were recorded using Nicolet Compact - 4
      (USA) in response to monaural auditory stimuli consisting of clicks of 100 ps
      square pulse at a rate of 15/sec. The BAERs were recorded on day 4 of their stay
      at 3200 m and 4300 m respectively. Findings indicated an increase in absolute
      peak latencies of wave V at 3200 m, which was statistically significant. On
      further ascent to 4300 m there was an increase in absolute peak latencies of wave
      I and III indicating delay in sensory conduction at the medullo-pontine auditory
      pathways.

PMID- 15521565
TI  - Respiratory functions in Kalaripayattu practitioners.
AB  - Kalaripayattu, an ancient traditional martial art form of Kerala, is considered
      as the basis for all martial arts viz. Karate, Kungfu, etc. physiological studies
      are more concentrated on Karate, Kungfu and other martial arts due to their
      global acceptance. Considering the limited knowledge available regarding the
      physiological profiles of Kalaripayattu practitioners, the present study was
      taken up for filling the lacunae in the field. Lung function tests were carried
      out in ten Kalari practitioners. Residual volume was measured by indirect method.
      Higher lung volumes and flow rates were achieved in Kalari practitioners compared
      to age and height-matched controls. Better mechanical factors and lower airway
      resistance influenced during Kalari practice might have benefited in improving
      hung volumes and flow rates.

PMID- 15521566
TI  - Phytochemical determination and extraction of Momordica charantia fruit and its
      hypoglycemic potentiation of oral hypoglycemic drugs in diabetes mellitus
      (NIDDM).
AB  - Momordica charantia (MC) fruit was subjected to phytochemical and pharmacological
      interaction studies with oral hypoglycemis in NIDDM patients. Phytochemical,
      chromatographical analysis and extraction of methanolic MC fruit soft (semi-solid
      form) in CCl4 + C6H6 solvent system yielded 15 diverse chemical constituents-
      alkaloids, glycosides, aglycone, tannin, sterol, phenol and protein. The CCl4 +
      C6H6 MC soft extract was used orally in a dose of 200 mg twice daily (BD) for
      pharmacological interactions with two diversely acting oral hypoglycemic agents-
      1) metformin BD and 2) glibenclamide BD in 15 patients of either sex (52-65 years
      of age) of NIDDM. It was observed that with CCl4 + C6H6 MC soft extract plus half
      doses of metformin or glibenclamide or both in combination caused hypoglycemia
      greater than that caused by full doses used in the study with 7 days treatment.
      Conclusively the extract acts in synergism with oral hypoglycemics and
      potentiates their hypoglycemia in NIDDM.

PMID- 15521567
TI  - Peripheral plasma FSH concentration in relation to expression of estrus in
      Sahiwal cattle (Bos indicus).
AB  - An experiment was conducted to investigate the changes in peripheral plasma FSH
      concentrations in relation to expression of estrus in Sahiwal cows. Out of total
      five estrus, three were accompanied by overt signs whereas rest two were silent
      estrus. In cows with overt estrus, plasma FSH concentrations during periestrus,
      early luteal, midluteal and late luteal phase were 1.65+/-0.34, 1.67+/-0.21,
      1.58+/-0.18 and 1.69+/-0.31 ng/ml, respectively and the corresponding values in
      cows with silent estrus being 0.68+/-0.39, 0.50+/-0.12, 0.75+/-0.13 and 0.46+/
      0.12 ng/ml, respectively. The overall plasma FSH levels in cows that exhibited
      overt estrus was 1.63+/-0.82 ng/ml as against 0.64+/-0.55 ng/ml in silent estrus.
      It was concluded that FSH levels were higher (P<0.01) in cows that exhibited
      overt estrus compared to silent estrus.

PMID- 15521568
TI  - [Dignity of the medical toxicologist in the context of medical ethos].
AB  - On beginning of article two sources of medical ethics: Hippocratic Oath and Good
      Samaritan (from the parable of Jesus Christ). First, it is paradigm of medicine
      from antiquity to present times, second this paradigm describes from side of
      Christian theology and anthropological dates. From point of sight of personalism
      of traditional source of medical, they make up foundation to appearance of
      dignity physician of toxicology. Notion of dignity contains many most important
      guild of physicians in our times, especially physician of toxicology. Principle
      part of article analyses dignity of physician in worry about life, co-operation
      with different doctors as well as in context of conscience and in challenges of
      future. Progress of clinical toxicology has to be connected with moral values and
      the dignity of medical profession and physician's status.

PMID- 15521569
TI  - Clinical status of carbon-monoxide-poisoned patients and the results of rest
      99mTc-MIBI and 99mTc-Amiscan heart scintigraphy performed in the acute phase of
      intoxication and stress-rest 99mTc-MIBI scintigraphy six month later.
AB  - The double tracer (99mTc-MIBI and 99mTc-Amiscan) scintigraphy is an useful
      technique to imagine cardiac injury due to CO intoxication. Accumulation
      (retention) of 99mTc-MIBI is dependent on blood flow and cellular and
      mitochondrial electrical potential of myocytes. The lower tracer accumulation is
      seen not only in necrotic heart tissue regions, but also in ischemic area of
      worse metabolic rate and perfusion. 99mTc-Amiscan contrary to 99mTc-MIBI, is
      accumulated only in regions of early necrosis so it can be can distinguished from
      transitory ischemia. Mechanisms of cardiac injury due to CO toxicity is different
      than due to coronary occlusion and the process of the heart damage is usually
      much longer. Results of control stress-rest 99mTcMIBI scintigraphy, performed
      after 6 months from CO exposure in relation to the clinical state on admission
      and results of 99mTc-MIBI and 99mTc-Amiscans scans obtained in acute phase of
      poisoning are presented in the study. Initial 99mTc-MIBI SPET examination had
      confirmed transitory myocardial ischemia of different degree in all the examined
      patients. The mutual dependence between degree of scintigraphic changes and blood
      lactate level and CK activity was found. 99mTc-Amiscan scintigraphy demonstrated
      areas of necrosis in myocardium of some patients; they had statistically higher
      COHb and blood lactate concentration compared to the rest. A control stress-rest
      99mTc-MIBI SPET performed 6 months after CO intoxication, confirmed a late
      consequences of metabolic abnormalities and a necessity of cardiovascular system
      follow-up controlling.

PMID- 15521570
TI  - Evaluation of regional cerebral perfusion using 99mTc-HmPAO single photon
      emission tomography (SPET) in carbon monoxide acutely poisoned patients.
AB  - Carbon monoxide (CO) poisoning continues to be a significant health problem. An
      early assessment of organs injury due to carbon monoxide poisoning is even more
      difficult than confirming the diagnosis of CO poisoning. Numerous neuroimaging
      techniques have been used to evaluate CO intoxication. The aim of this pilot
      study was to estimate the regional cerebral perfusion in CO acutely poisoned
      patients using 99mTc-HmPAO SPET. Disturbances in cerebral perfusion mainly in
      frontal, parietal cortex and basal ganglia were observed in 17 (85%) of 20
      examined CO poisoned patients. 99mTc-HmPAO scintigraphy seems be useful in
      demonstration of early CNS dysfunction and estimation to what extent perfusion
      abnormalities influence the brain injury. A further study to evaluate the rCBF in
      relation to poisoning severity scoring are needed.

PMID- 15521571
TI  - [Difficulties in diagnosis of hepatic encephalopathy in ethanol dependent
      patients].
AB  - As a somatic evaluation by outpatient psychotherapy service for alcoholics is
      being done very rarely the patients are not informed about health harm related to
      alcohol having the "false feeling of safety". The aim of the study was to
      evaluate a functional and morphological liver state of patients served by such a
      service for minimum 5 years who were sent do the Department of Clinical
      Toxicology via intervention medicine. The changes in the central nervous system
      were also considered. The West Haven criteria of altered mental state in hepatic
      encephalopathy were applied. The Number Connection Test, part A and B, and "100
      7" test were used to psychometric evaluation. A significantly higher serum
      ammonia concentration (p<0.02), AST, ALT and GTP enzymes activity, bilirubin
      (p<0.02), iron (p=0.005) concentration and significantly lower prothrombin index
      and albumin concentration were found in the group of ethanol dependent patients
      as compared to the reference group. A significantly lower RBC and platelets
      number, lower Ht and significantly elevated MCV compared to the control group
      were also found. The relationship between West Haven criteria and results of
      laboratory testing was shown: a worse West Haven criteria a worse metabolic
      disorders. The pathologic changes in the liver ultrasonography and scintigraphy
      were significantly higher in the group of ethanol dependent patients. The
      presented observations indicate on necessity of close co-operation between
      psychologists, therapeutics and clinical toxicologists in early diagnosing and
      treatment the organ injury in alcohol addicted patients.

PMID- 15521572
TI  - [Morphologic and functional status of the liver in patients with acute ethanol
      intoxication and chronic alcoholism].
AB  - Current work is a continuation of the already published study on usefulness of
      enzymatic tests, biochemical parameters and ultrasonography for evaluation
      ethanol hepatotoxicity but histology testing of the liver bioptates is
      additionally included. Under examination there were 139 ethanol dependent
      patients admitted to the Department of Clinical Toxicology Jagiellonian
      University Medical College because of severe ethanol intoxication. The reference
      group comprised 30 healthy men, not exposed to hepatotoxic agents. Chosen enzymes
      activity and biochemical parameters were measured (before and after 3 weeks long
      controlled abstinence) and ultrasonography was performed in both the groups. Due
      to clinical indication the USG guided liver biopsy and histology testing was done
      in 20 patients from the ethanol dependent group. 68 of ethanol dependent patients
      underwent the post-abstinence control ultrasonography. A normalization in AST and
      ALT activity (p<0.001), bilirubin and Fe concentration as well as serum albumin
      elevation was noted in the ethanol dependent patients after controlled
      abstinence. The mean values of GGT, LDH, and PA activity were significantly
      diminished compared to the initial examination, but still significantly higher
      compared to the control group. The three weeks long abstinence did not change MCV
      and prothrombin index. The pathologic changes in liver ultrasonography were
      significantly higher in the group of ethanol dependent patients both in acute
      phase of intoxication and after abstinence and principally reflected the bioptate
      histology testing.

PMID- 15521573
TI  - [Apoptosis of bronchoalveolar lavage lymphocytes (L-BAL) in pneumoconiosis].
AB  - BACKGROUND: The appearance and extension of apoptosis phenomenon in lymphocytes
      originated from the lower airways of patients with pneumoconioses, including
      silicosis and asbestosis, as well as its relation to the clinical data, remains
      unclear. METHODS: Bronchoalveolar lavage (BAL) was carried out in 11 patients
      with silicosis, 8 with asbestosis and in 7 control subjects. L-BAL were a)
      studied for CD95 and CD95 Ligand expression, b) permeabilized and stained with PI
      (flow cytometry, ModFit software) for apoptosis/cell cycle analyses and c)
      stained with Annexin V FITC/PI. RESULTS: The low number of L-BAL enter apoptosis.
      No significant changes between studied groups were found in PI determined
      apoptosis (silicosis: 1.8 +/- 0.7%, asbestosis: 3.1 +/- 0.9%, controls: 1 +/-
      0.7%, median +/- SEM). Similar results were obtained, if tested with Annexin V
      FITC. However, the asbestosis group was characterized by higher CD4/CD8 ratio and
      increased percent of L-BAL CD95 Ligand expression (21.0 +/- 4.5 vs 13.7 +/- 3.3
      in controls). In silicosis L-BAL apoptosis was inversely correlated with FEV1/VC
      values (r=-0.26, p<0.05). Surprisingly the majority of BAL lymphocytes expressed
      CD95, the marker of cell susceptibility to apoptotic stimuli; no difference
      between studied groups was found. CONCLUSIONS: Lower airways lymphocytes seem to
      be prevented from excessive apoptosis. Tendency to slightly increased percent of
      apoptotic and/or Fas Ligand cells reflects likely the local immunity alterations
      in asbestosis patients.

PMID- 15521574
TI  - [Micronuclei as markers of DNA damage in patients addicted to opioid drugs].
AB  - The goal of the study was to examine the influence of methadone maintenance
      treatment programme on instances of DNA damage manifested in the micronuclei. The
      material of the study (cultures of lymphocytes from peripheral blood) obtained
      from 12 opiate dependent patients was taken two times: at the start of and during
      the course of a methadone programme conducted at the Department of Clinical
      Toxicology of the Jagiellonian University's Medical College. The observed
      decrease in the number of micronuclei indicates that this type of treatment in
      conjunction with appropriate life style changes on the part of the subjects
      reduces the risk of genomic lesions.

PMID- 15521575
TI  - [The frequency of micronuclei in lymphocytes from cord blood as a marker of
      exposure to mutagenic factors].
AB  - The aim of the study was a preliminary recognition of effect of mutagenic factors
      which passed through placenta and influenced cells of the foetus during third
      trimester of the pregnancy. The research group of being studied was 31 newborns,
      born at the Department of Gynaecology and Infertility of Jagiellonian University
      Medical College in Krakow, and their mothers. The neonates (cord blood) and
      mothers (peripheral blood) were examined for presence of micronuclei (MN) in
      cultured lymphocytes by using the whole blood method. Significant difference
      between mother's and neonate's frequencies of micronuclei indicates on less
      exposure to genotoxic factors of neonates.

PMID- 15521576
TI  - [Preliminary study of the frequency of micronuclei in buccal mucosa cells sampled
      from patients with laryngeal tumors].
AB  - The examination of frequency of micronuclei was carried out on two groups of
      patients with tumors of upper respiratory tract: cancer of larynx (36
      individuals) and polyps of larynx (13 persons). Groups of habitants from
      Katowice, Czestochowa and Nowy Sacz (cities with the different level of air
      pollution) and separately group of smokers, were considered as the control. It
      was observed that high frequency of micronuclei in cell of buccal mucosa from
      individuals exposed on mutagenic substances from the air and cigarette smoke
      could be a marker of higher risk of carcinogenesis.

PMID- 15521577
TI  - Chemical poisonings among Krakow inhabitants in 1972 and 2002.
AB  - The patterns (frequency, poisoning type, toxic agent involved) of adolescent and
      adult poisonings in Krakow in 1972 and 2002 are presented. The analysis includes
      data for poisoned patients treated at the Krakow Department of Clinical
      Toxicology in 2002 and 1972, and all on the spot fatal cases subjected to post
      mortem autopsy and toxicological examinations at the Department of Forensic
      Medicine in both the years. As much as 4116 poisoned cases (males 2722; females
      1394) were treated in 2002 compared to 1485 (males 649; females 836) in 1972.
      There was no substantial difference between a number of poison related fatalities
      on the spot in years analysed: 126 (males 105; females 21) in 2002 and 122 (males
      84; females 38) in 1972. An elevation in poisoning incidence rate per 10,000 of
      Krakow inhabitants was also noted in 2002 compared to 1972 (54.3 vs. 30.0). A
      pharmaceuticals (32.9%) followed by CO (18.2%) and mixed pharmaceuticals (16.2%)
      were mostly involved in poisoning cases in 1972, whereas ethanol (46%),
      pharmaceuticals (13.2%), pharmaceuticals co-ingested with ethanol (7.8%),
      narcotics (7.8%), mixed pharmaceuticals (6.7%), and CO (5.2%) were mostly
      involved in poisoning cases treated in 2002. A mortality rate both concerning
      only a people who died in hospital or/and those who died on the spot (prior to
      any treatment) was significantly higher in 1972 compared to 2002.

PMID- 15521578
TI  - [Gastric lavage, hemodialysis and specific antidotes in acutely poisoned patients
      treated at the Specialist Hospital in Biala Podlaska (1993, 2001 and 2002)].
AB  - Gut decontamination, the methods of extracorporeal elimination of poisons and
      antidote use are the specific measures in clinical toxicology. Statistically they
      are not often used in intoxicated patients. It is not known, in how many cases of
      poisoning treated outside toxicological units are they applied. Approximately 110
      poisoned patients were hospitalised each year in the Specialist Hospital in Biala
      Podlaska in years 1993, 2001 and 2002. Gastric lavage was performed in about 50
      percent of those cases, especially often in children up till third year of life
      and in the cases of poisoning with medical drugs. The Gut Decontamination
      Position Statement of AACT and EAPCCT, published in 1997, had no significant
      impact on use of decontamination procedures in our hospital. Haemodialyses were
      performed in 3-5% of poisoned patients. All those patients were poisoned with
      ethylene glycol or methanol. Only 4 specific antidotes were used in years 1993,
      2001 and 2002. The most commonly used antidote was ethanol, despite its level is
      not measured in our laboratory. Recommendations for gut decontamination should be
      widely popularised. The use of activated charcoal may be in many cases more
      suitable as a gastric lavage. Safe and effective use of ethanol as an antidote in
      a hospital requires its measuring in own laboratory.

PMID- 15521579
TI  - [Suicidal behavior and suicide attempts in adolescents and young adults-
      epidemiology, risk factors, prevention and treatment].
AB  - According to WHO, every year, suicide is committed by at least 1 mln people in
      the world. In Europe, suicide is committed by about 43 thousand people a year,
      most frequently by middle-aged and elderly males, and attempted by 700 thousand
      people. In Poland, in 2002, 5100 people committed suicide. The number of suicide
      attempts is probably ten times higher. The aim of the study is to investigate the
      current state of knowledge concerning suicidal behaviour and attempted suicide in
      adolescents and young adults. The literature on the subject is analysed, and
      special attention is paid to the issue of suicide epidemiology, risk factors,
      prevention and treatment. Definitions of suicidal behaviour and presuicidal
      syndrome are debated. In the chapter concerning treatment, Bohme's model of
      crisis intervention in the case of suicidal patients is discussed, and detailed
      indications for treatment are presented. Suicide attempts are undertaken most
      frequently by young people, especially by teenage girls and young women. The
      ratio of suicide in this age group increased significantly in the last few years.
      Phenomena which are of special importance for the prevention of suicide among
      adolescents include suicidal thoughts, attempted suicide, and completed suicide.
      Multicentre study into suicidal behaviour conducted by WHO indicate that the
      highest average yearly European coefficients of suicide attempts have been
      detected in young females ranging in age from 15 to 24 years. Polish and foreign
      literature on the subject is dominated by publications regarding completed
      suicide. The issue of attempted suicide is treated rather marginally, which may
      be due to the scantiness of reliable data concerning large populations. The past
      few years, however, brought a significant advancement of the research into the
      epidemiology, etiology, and treatment of suicidal behaviour in adolescents. It is
      difficult to establish linear correspondence between risk factors and suicidal
      behaviour. The cause is usually a combination of constitutional factors including
      genetic ones, earlier personal experiences, and precipitating stressful events.
      Paradoxically, the risk of suicide among adolescents increases in highly
      developed countries, where the quality of life has undergone a significant
      improvement. In conclusion, the authors have stressed the importance of an
      interdisciplinary approach to work with individuals endangered by the risk of
      suicide. Attention has also been drawn to the importance of personal contact and
      the necessity to accompany the individual in suicidal crisis from the beginning
      to the end of the therapy.

PMID- 15521580
TI  - [The frequency of suicide attempts depending on gender and the age structure].
AB  - Sex and the age structure have been for decades the crucial factors determining
      the dimensions of suicide. In the literature of the subject, it is possible to
      find different interpretations concerning the widely known facts of larger
      effectiveness of suicide among males. Females, on the other hand, exhibit
      suicidal behaviour and suicide attempts several times bigger than the number of
      completed suicides. In comparison with wide literature dealing with the
      problematic of completed suicide, the number of publications concerning suicide
      attempts is, both in foreign and in Polish literature rather scarce. That is why
      the present authors have undertaken the analysis of suicide attempts by subjects
      hospitalized in the Department of Clinical Toxicology Jagiellonian University
      College of Medicine in Krakow in the years 2000-2002. On the basis of the medical
      documentation, 2757 cases of attempted suicide through self-intoxication by
      subjects undergoing treatment in the toxicological department. In the period
      concerned, the number of hospitalizations after suicide attempts increased from
      856 cases in the year 2000 to 971 cases in 2001, and subsequently slightly
      decreased to 930 cases in 2002. The highest indicator of suicide attempts through
      self-intoxication has been observed among adolescents and young adults. In the
      absolute values, within the span of the years in question, there is a substantial
      predominance of suicide attempts undertaken by adults ranging in age from 20 and
      50. On the contrary, in the oldest age group (over 60), the number of suicide
      attempts through self-intoxication was in the years concerned the lowest. In
      contrast with completed suicide, where the proportion of males to females is 4:1,
      in the group examined, females constituted 50% of subjects after suicide
      attempts. The number of females after suicide attempts in the consecutive years
      analysed was higher among adolescents and young women under 30. Despite drawbacks
      in data gathering, there is convincing testimony indicating that suicide is the
      result of number of complex risk factors. Sex and the age structure belong to non
      modifiable factors, and thus emphasis should be put on the importance of the
      gathering of relevant data and on further research into the factor of sex and age
      structure in suicide attempts and completed suicide.

PMID- 15521581
TI  - [Fluctuations and seasonality in suicidal attempts].
AB  - The aim of the study was to analyze seasonality and temporal fluctuations in
      suicide attempts by persons living in Krakow and hospitalized in the Department
      of Clinical Toxicology CMUJ in the years 2000-2002. The research focussed on the
      frequency of suicide attempts in relation to the time of the day, day of the
      week, and month of the year. Temporal fluctuations in the frequency of suicide
      attempts have been assessed on the basis of the data from medical documentation
      concerning 2757 suicide attempts by individuals ranging in age from 14 to 90
      years. The group consisted of 1607 females and 1150 males. According to the
      results of the research, seasonality and temporal fluctuations in the frequency
      of suicide attempts is different for males and females. In the case of the males
      examined, no dependence between the frequency of suicide attempts and a
      particular month or season has been observed. In the case of females, on the
      contrary, the data indicate the existence of a seasonal pattern with the peak in
      the spring (or early part of the summer), and in the autumn--in October and
      November. In males, the peak day for attempted suicide was Monday, whereas in
      females--Sunday and Monday. As regards the time of the day, both the results of
      the present research and data collected by WHO/EURO indicate that suicide
      attempts occurred most frequently in the evening, late in the evening or in the
      early part the night. In conclusion, it has been emphasized that the majority of
      suicide attempts, especially by females, occurs late in the evening or early in
      the night. This finding seems to be of particular importance for suicide
      prevention--it can contribute to the increase in the effectiveness of the
      organization of work in the Crisis Intervention Centres and make therapists and
      patients' families aware of the existence of periods of an increased suicide
      risk. The research has been conducted owing to the cooperation between the
      department of Clinical Toxicology, CMUJ and the Department of Adult Clinical
      Psychiatry, CMUJ in Krakow. The results obtained, together with the results of
      the research conducted by the centres participating in WHO/EURO are vital for
      suicide prevention and treatment.

PMID- 15521582
TI  - [Risk factors for suicide attempts in elderly and old elderly patients].
AB  - The aim of the study was to assess the phenomenon of suicide attempt in the
      elderly inhabitants of Krakow. Special attention has been paid to the group of
      "seniors"--aged 75 years or over. The authors have analyzed all the 136 cases of
      suicide attempts by individuals aged over 60 years, selected from the cases of
      suicide attempts by self-intoxications by patients hospitalized in the Department
      of Clinical Toxicology, CMUJ in Krakow in the years 2000-2002. The group
      concerned included 45 males and 91 females. A large number of subjects (over a
      half of the total) ranged in age from 60 to 65 years. The group of seniors
      comprised 35 individuals (aged 75 years or over), including 7 males and 28
      females. On the basis of the data from medical documentation, the subjects were
      analysed from the point of view of their health condition and in the psycho
      social context. In the majority of cases the subjects are pensioners residing in
      Krakow, often living alone. In the case of 98% of the subjects, it was their
      first suicide attempt. Pharmaceuticals used for self-poisoning were most
      frequently psychotropic, or mixed-type drugs. The assessment of the severity of
      poisoning indicates that in about 20% patients poisoning was severe. 70% of the
      subjects suffered from depressive, reactive, or situational disorders, affective
      depression or organic brain disorders, often with dementive signs. A significant
      number of subjects suffered from hypertension, coronary artery disease,
      arteriosclerosis, or alimentary tract diseases. In the group of the seniors, the
      most conspicuous problems included serious somatic diseases (malignant diseases
      and chronic respiratory system diseases), depression, organic dementia,
      loneliness, and bad family situation. Taking into consideration the scantiness of
      research into attempted and completed suicide in the elderly and in the old
      elderly, the present authors stress the importance of the continuation of the
      research to prevent suicide in the aforesaid age group.

PMID- 15521583
TI  - [Attempted suicide among teenagers and young adults].
AB  - The aim of the study was to present the phenomenon of suicide attempts by self
      poisoning in a group of females and males ranging in age from 15 to 29 years, and
      treated in the Department of Clinical Toxicology Jagiellonian University College
      of Medicine in Krakow in the years 2000-2002. The group analyzed comprised of
      1117 patients, 629 (69.1%) women and 425 (38.1%) men. In the female group,
      teenagers under 19 constituted 48.9%, whereas young females ranging in age from
      20 to 29 years--51.1%. In the male patients group teenagers under 19 constituted
      29.4%, the young men (20-29 years of age)--70.6%. The group was analyzed from the
      point of view of demographic, clinical and social factors such as gender, age,
      level of education, marital status and occupation (if applicable), the course of
      self-poisoning and kind of toxic substance involved. In the majority of cases,
      self-poisoning had been caused by taking one type of medicines, and less
      frequently by taking mixed-type medicines or by simultaneously taking medicines
      and ethanol. The most typical drugs used in the attempts included
      benzodiazepines, phenothiazines, nonsteroidal antiinflammatory and antiepileptic
      drugs. The assessment of the poisoning severity based on the PSS classification,
      indicates the predominance of the minor and moderate poisoning. Up to 50% of
      subjects suffered from mental disorders--most frequently from affective
      disorders, neurotic disorders, and personality disorders. As an essential part of
      the problem of suicidal behaviors in teenagers and young adults, suicide attempts
      among young population require an in-depth analysis. The scale of the problem
      indicates the necessity of initiating appropriate preventive actions and
      organizing appropriate psychological and psychiatric care.

PMID- 15521584
TI  - [MMPI- and BDI-scale-based self-assessment of the psychic condition of patients
      after a suicidal attempt].
AB  - Parasuicide (suicidal attempt) is an intentional, self-aggressive behaviour
      intended to damage the body rather than cause death. About 75% of suicidal
      attempts are those committed for the first time. The majority of suicidal
      attempts are impulsive. About 66% of the parasuicide patients said that they had
      thought about the act for less than an hour beforehand. Only 30% of the patients
      had been psychiatrically diagnosed before they were admitted to the hospital.
      After prompt re-diagnosing, the percentage was considerably lower. The aim of the
      work is to analyse, using Minnesota Multiphasic Personality Inventory (MMPI-DMS
      subscale) and Beck Depression Inventory (BDI), the self-assessment of the
      psychical condition of patients hospitalised at the Acute Poisonings Clinic,
      Nofer Institute of Occupational Medicine, Lodz, Poland, for attempted suicide.
      The study subjects included 222 patients (148 women and 74 men) treated in 2003.
      The control comprised 137 volunteers random-selected from among patients visiting
      Institute's Outpatient Clinic of Occupational Diseases. The psychiatric testing
      revealed mood and personality disorders, and acute stress disorders. Depression
      or other psychotic reactions were not diagnosed in any of the cases. Mean MMPI
      subscale scoring for the women was 10.7 (subjects) and 3.5 (control). The MMPI
      rating after 6 months since the attempted suicide was 6.03, i.e. by 4.3 scores
      lower. The corresponding values for the men were 10.1 (subjects) and 3.06
      (control), and after 6 months the value was 4.64, by 5.46 scores lower. Mean BDI
      scale scoring for the women was 10.56 (subjects) and 7.9 (control). The BDI score
      after 6 months since the poisoning was 7.74, i.e. by 2.83 scores lower. The
      corresponding values for the men were 10.77 (subjects) and 5.27 (control), and
      after 6 months the value was by 2.86 scores lower. The results are statistically
      significant (p<0.001). CONCLUSION: The results show that 6 months after the
      suicidal attempt, the self-assessment of patients' psychical condition improves,
      the mood normalises. The suicidal attempt is often an impulsive act intended to
      relieve the rapidly growing stress.

PMID- 15521585
TI  - [Connection between personality and emotional intelligence in groups of patients
      after suicidal attempts and ethanol dependent persons].
AB  - The aim of the study was to examine relationship between personality and
      emotional intelligence in two groups. The first group included patients
      hospitalized for suicide attempts in the Department of Clinical Toxicology CMUJ,
      the second one included ethanol dependent patients hospitalized in detoxification
      unit. The study included 103 persons: 52 in the study group of patients after
      suicidal attempt and 51 in the ethanol dependent patients group. Personality was
      described according to the one of most popular concepts--Costa and McCrae's Big
      Five Model, including five major factors: neuroticism, extraversion, openness to
      experience, agreeableness and conscientiousness. The second problem discussed in
      this study was emotional intelligence understood as ability to follow one's own
      and others' emotions, differentiate them and use this information in directing
      one's own thinking and action. In this study Costa and McCrae's Five-Factor
      Inventory (NEO) and N. S. Schutte's Emotional Intelligence Questionnaire were
      used. The analysis of their results in our two groups confirmed the hypothesis of
      relationship between emotional intelligence and personality.

PMID- 15521586
TI  - [Results of the psychological examination of patients--alcohol-addicted drivers,
      treated in a detoxification unit].
AB  - There are many studies on problems related to alcohol abuse in many aspects from
      many countries. As a preventive strategy a few years duration programs for
      numerous populations are being conducted for tightening of social interrelation,
      to prevent juvenile drinking, to avoid drinking and driving etc. USA study on
      drinking and driving people indicate on different psychiatric disorders and needs
      for deeper psychiatric insight. Analysis of different source information on
      alcohol related traffic collisions is a basis for prevention strategy programs.
      Our study may contribute in small number of psychology publications related to
      psychometric testing on motor skills, cognition ability and social condition of
      people who drive and drink. There were 50 ethanol dependent patients treated at
      the Department of Clinical Toxicology detoxification unit. All of them had a
      driving license; majority had access and opportunity to drive a car. A structured
      interview and psychometric tests were used to evaluate psychology functioning. It
      can be assumed that deficits revealed in the examination may be detrimental
      factors to proper and efficient driving ability.

PMID- 15521587
TI  - [Somatic and psychiatric disorders in alcohol-addicted patients treated in a
      detoxification unit].
AB  - The aim of the presented study was the assessment of somatic and psychiatric
      disorders in alcohol addicted patients, treated in the Department of Clinical
      Toxicology detoxification unit in Krakow in 2002 year. The total number of 443
      patients (377 men and 66 women) were considered for the research. More than 50%
      patients were hospitalized repeatedly (2 or more times) due to alcohol problems.
      Medical history as well as detail medical examination and diagnostic evaluation
      revealed the concomitance with alcohol disease different somatic illnesses and
      psychiatric disorders. In 194 patients (43.8%) the alcoholic liver damage was
      diagnosed, frequently (in 5.2% patients) with chronic pancreatitis. Only 22
      patients (5%) were infected with hepatitis virus type B. Diabetes type 2 and
      different cardiovascular disorders were present in almost one third of patients.
      In the past 55 patients (12.4%) have had severe head trauma, and 51 (11.3%) were
      treated because multiorgan trauma. Psychiatric examination revealed in 102
      patients (23%) affective disorders, and in 92 (20.7%) personality disturbances.
      The presented data should be a ground for discussion about treatment model
      alcohol dependency in Poland.

PMID- 15521588
TI  - [Chronic ethanol abuse related hospitalisation in the Internal Medicine
      Department of the Specialist Hospital in Biala Podlaska (Poland)].
AB  - The admission to a hospital and abrupt cessation of drinking often provokes an
      alcohol withdrawal syndrome in an alcohol dependent patient. The patients
      hospitalised in relation to chronic ethanol abuse in years 2001-2002 at the
      Internal Medicine Ward of the Specialist Hospital in Biala Podlaska were
      subjected to the study. In those years alcohol related patients made 2 and 3% of
      the total amount of patients, respectively. Among the patients, men aged 40-49
      years old prevailed. The most common diagnoses in the analysed group were:
      alcoholic liver disease, liver cirrhosis and acute pancreatitis. In the treatment
      of withdrawal symptoms diazepam was used. Only few percent of patients in the
      analysed group needed physical restraints because of their great agitation. Early
      recognition and correct treatment of threatening alcohol withdrawal syndrome
      diminishes the risk of severe symptoms and complications.

PMID- 15521589
TI  - [Alcohol dependent patients in family doctor's practice in Gdansk].
AB  - Polish family doctors have been given legal rights to diagnose and treat patients
      with alcohol dependency. Unfortunately, majority of general practitioners do not
      have proper knowledge and motivation required for this kind of treatment. The aim
      of the study was to evaluate the preparedness of family doctors in Gdansk to
      diagnose and treat patients with alcohol dependency. Fifty family doctors from
      Gdansk were included in the study. Forty five agreed to answer the anonymous
      questionnaire. Forty two out of 45 family doctors did not know the basic notions
      connected with diagnosis and therapy of alcohol dependency. The screening tests,
      helpful in the diagnosis of alcohol dependency, were not used by general
      practitioners--42 of them (almost 94%) did not treat alcohol abusers
      pharmacologically, and 18 (aprox. 40%) did not have time for such patients. It
      seems that there is an urgent need to provide further education for general
      practitioners and make better use of the existing structures engaged in the
      diagnosis and therapy of alcohol abusers.

PMID- 15521590
TI  - [Acetaldehyde concentration in acute ethanol-intoxicated patients addicted to
      alcohol].
AB  - Ethanol is oxidized to acetaldehyde by alcohol dehydrogenase (ADH) and this is
      the main way of alcohol oxidizing in social drinkers. Microsomal Ethanol
      Oxidizing System (MEOS) is induced in ethanol addicted individuals and plays the
      main role in ethanol oxidation in this group. The aldehyde dehydrogenase (AIDH),
      enzyme oxidizing acetaldehyde to acetic acid, activity is not induced and does
      not get changed. This may lead to acetaldehyde cumulation in alcoholics. The aim
      of the study was to define the usefulness of acetaldehyde concentration
      measurement in the blood as the marker of alcohol addiction. 53 alcohol addicted
      and acutely poisoned patients (males) participated in the study. The control
      group was social drinkers, 43 males, accidentally poisoned with ethanol. Alcohol
      addiction was diagnosed according to ICD-10 criteria. Ethanol and acetaldehyde
      measurements were carry out on admission. The ethanol concentration in blood was
      measured by enzymatic method (ADH) and acetaldehyde concentration using headspace
      gas chromatography. Because of differences of ethanol concentrations in two
      examined groups (alcoholics and social drinkers) the normalization of
      acetaldehyde results was performed dividing acetaldehyde concentration by ethanol
      concentration. The results indicated higher blood acetaldehyde and ethanol
      concentrations in alcoholic individuals acutely poisoned with ethanol in
      comparison to acutely poisoned social drinkers. The acetaldehyde/ethanol ratio,
      used in the study, is higher in alcoholics as well and the difference is
      statistically significant. These results suggest the usefulness of acetaldehyde
      concentration measurement as a marker of ethanol addiction.

PMID- 15521591
TI  - [Clinical aspects of acute intoxication with ethanol].
AB  - Acute ethanol intoxication and pathologies resulting from its chronic usage are
      among the most common causes of hospitalization in many countries, affecting all
      age groups, both genders and almost all social groups. The aim of the study was
      to evaluate chosen clinical aspects of acute intoxication with ethanol among
      patients admitted to the Department of Toxicology from 2002 to 2003. Data of 180
      patients with acute ethanol poisoning were analyzed. There were 29 women aged
      from 15 to 65 (mean 33.9 +/- 15.7) years and 151 men aged from 13 to 75 (mean
      39.3 +/- 14.8) years in the group. The alcohol addiction was the most common
      among men (68.9%), and the people over 30 years old (53.9%). In the adolescents
      (up to 18 yrs. old) the serum ethanol level was significantly lower but the coma
      grade was higher then in the adult group. There were 20 patients in deep coma (IV
      grade according to Matthew scale), 6 of whom (3.3% of the intoxicated persons)
      had acute respiratory failure with the necessity of invasive mechanical
      ventilation. There were 95 (52.8%) patients with transient elevation of creatine
      kinase activity from 191 to 14,616 (mean 1056.4 +/- 2604.3) U/L, and 18 (10%)
      patients with transient serum creatinine concentration elevation (max. 1.8
      mg/dl). CONCLUSIONS: The percentage of the addicted to ethanol were significantly
      higher among men (male to female 1:8.7), and patients over 30 years old. Despite
      the significantly lower serum alcohol level in adolescents the grade of coma was
      higher than in the adult group. There were 6 patients in deep coma and acute
      respiratory failure who required invasive mechanical ventilation.

PMID- 15521592
TI  - [Assessment of disorders after chronic psychoactive drug abuse in patients
      hospitalized in detoxification units].
AB  - The aim of this study was the assessment of disorders after chronic intake of
      psychoactive drugs, like marijuana, amphetamine, ecstasy, cocaine and opiates. In
      2002 in the Department of Clinical Toxicology detoxification unit were treated
      117 chronic drug abusers. The 76 of them use the opiates predominantly, the next
      41 persons (35 men, 6 women), were heavy abusers of psychostimulant drugs. In
      opiate abusers typical withdrawal signs and symptoms were observed. In the group
      of psychostimulants users, the mean time of marijuana use was 6 years,
      amphetamine--5 years. The cocaine was used rarely. Among 25 persons (61%) from
      these group the withdrawal syndrome were established. The excitation of
      neurovegetative system, depression, or psychomotor effects were observed. We
      concluded the necessity of estimation of neurobiological changes after using of
      psychostimulants and that more controlled research might uncover a clinically
      diagnosable withdrawal syndrome in human psychostimulants users.

PMID- 15521593
TI  - [Psychoactive drug dependent patients in family doctor's practice in Gdansk].
AB  - Recently the number of drug addicts has increased considerably in the whole world
      as well as in Poland. Since this phenomenon's growing tendency, health service
      management would like general practitioners to take more active part in dealing
      with drug addicts. The aim of the study was to evaluate the preparedness of
      family doctors in Gdansk to diagnose and treat drug addicts. Fifty family doctors
      from Gdansk were included in the study. Forty five agreed to answer the anonymous
      questionnaire. Twenty one family doctors (46.7%) considered their knowledge about
      diagnosis and therapy of drug addicts as insufficient. There were only 8 family
      doctors (17.8%) routinely asked patients about drug abuse. The quick intervention
      was not used by any of general practitioners. It seems that there is an urgent
      need to provide further education for general practitioners concerning drug
      abusers.

PMID- 15521594
TI  - [Psychoactive substances in biological samples--toxicological laboratory data].
AB  - The subject of the research was the analysis of frequency and type of
      psychoactive substances used, basing on the determinations the blood and/or urine
      samples, performed in the toxicological laboratory of the Department of Clinical
      and Industrial Toxicology Jagiellonian University in Krakow in the period from
      December 2001 to November 2003. From 17,649 performed determinations--45.5% were
      positive. 50% of the positive determinations were psychoactive substances. The
      most often psychoactive substance determined was ethyl alcohol (52.86%), next
      benzodiazepines (17.41%), amphetamines (10.54%), opiates (8.05%), THC (6.87%),
      barbiturates (3.74%), and occasionally atropine and cocaine. There was observed a
      variety of mixed, simultaneously taking psychoactive substances, especially ethyl
      alcohol, opiates, amphetamine derivatives and cannabinoids. The analysis of the
      occurrence of psychoactive substances in biological samples from patients treated
      in different hospital departments, others hospitals and ordered by private
      persons also was performed. In the last two years 369 private patients ordered
      psychoactive substances determinations and 78 of them were positive.

PMID- 15521595
TI  - [Assessment of the legal awareness regarding drug consumption].
AB  - The latest legislation against drug addiction has changed the approach of
      Pursuing Organs in Poland to the problem of taking and distribution of drugs.
      Many tests have been carried out in order to evaluate the extent of legal
      regulations as the appropriate instrument in the struggle against drug addiction.
      The survey and interview were introduced during the research. The results make it
      possible to form the following conclusions. Law, only as a supplementary means
      supporting other methods may help prevent and counteract the addictions. Legal
      regulation on drug addiction which are based on compulsion and punishment should
      be widely taken into account.

PMID- 15521596
TI  - [Intake of nutrients in daily nutritional ratios by opiate dependent persons
      during methadone maintenance therapy].
AB  - The aim of the study was the evaluation of the nutritional habits of the opiates
      dependent persons before and during methadone maintenance treatment. We examined
      48 persons (36 males and 12 females) three times: first time before the methadone
      treatment, then after 2 months of treatment, and third time after 9 months of
      treatment. During each examination we performed 24-hour recall four times.
      Collected data were processed by author's software in order to get information
      about daily supply of main nutrients (proteins, fat, fatty acids, carbohydrates,
      dietary fibre, cholesterol), minerals (calcium, iron, phosphorus, zinc, sodium)
      and vitamins (vitamin A, B1, B2, niacin, C). The changes between the results of
      following examinations were tested by using the t-Student test. The results were
      compared with daily norms recommended on the safe level of intake for each age
      and gender group. In the majority of cases the diet of examined persons was quite
      reach in protein, but we noticed too low daily intake of fats, essential fatty
      acids, some minerals (calcium, iron, magnesium, zinc) and vitamins B1, B2 and C.
      After 2 months of methadone treatment the daily intake of fats, saturated fatty
      acids, essential fatty acids, cholesterol, dietary fibre, some minerals and
      vitamins decreased in men group, but in the last examination we noticed renewed
      growth in quantity of those nutrients in daily diet of examined persons. We did
      not observe it in the group of women.

PMID- 15521597
TI  - [Nutritional status of opiate-dependent persons before and during methadone
      maintenance therapy].
AB  - The aim of the study was to evaluate the nutritional status of opiate dependent
      patients who where classified to participate in the methadone maintenance
      treatment and to give the answer to the question how the nutritional status of
      these patients was changing during this programme. We examined 48 persons (12
      women aged 21-37 years and 36 men aged 20-46 years). All of them were
      participants of the methadone maintenance treatment. The patients were examined
      three times: first time just before the methadone treatment, then after 2 months
      and third time after 9 months of treatment. The anthropometrics measurement: body
      weight and height (it allowed us to calculate the BMI), two skin fat folds and
      the measurements of the body composition (using the bioimpedance method) were
      performed. The changes between the results of subsequent examination were tested
      using the t-Student test. As a result of the first examination we showed out that
      the majority of patients had a proper nutritional status evaluated by BMI. Poor
      nutritional status has been more often found than excessive nutritional status
      among examined patients, especially in the group of women. During the nine months
      of methadone maintenance treatment the statistically significant growth of body
      weight was observed and it derived from the increasing fat body mass and muscle
      mass. As a result of that we noticed the diminishing number of underweight
      people. More of examined people had overweight and in the group of men even
      obesity.

PMID- 15521598
TI  - [Use of a questionnaire and biomarkers for evaluation of tobacco smoking in
      parturient women].
AB  - According epidemiological study tobacco smoking is popular addiction around the
      world. It was estimated, that one third of world population smoking tobacco. The
      statistical data from 2002 show that in Poland 42% of men and 22% of women smoke
      tobacco on a daily basis. As many as 60% of non-smokers are exposed to
      environmental tobacco smoke (ETS). The aim of the study was verification the
      answer on a standardised survey questionnaire (related to tobacco smoking) by
      laboratory method--determination of cotinine in urine. In the study participated
      244 delivering women. In the tested group 23.8% of surveyed declared smoking
      during their pregnancy and around 28% of non-smoking women were exposed to
      passive inhalation of tobacco smoke. More than 15% of women, which declared non
      smoking has concentration of cotinine higher than 50 ng/mg creatinine (mean 227.3
      ng/mg creatinine) what indicated active smoking of cigarettes. From these results
      we can conclude that as much as 35.6% of women smoking tobacco during pregnancy
      and is higher than suggested the questionnaire examination.

PMID- 15521599
TI  - [Select parameters of renal function in smokers in correlation with the exposure
      to cadmium].
AB  - Cigarette smoke contains about 4000 chemical substances, including toxic metals
      such as cadmium. Smoking of 20 cigarettes a day results in inhalation an average
      3.6-6.0 microg of cadmium. Due to nephrotoxic action of some components of
      tobacco smoke, and especially cadmium, the present study was aimed to evaluate of
      chosen parameters of kidney status in cigarette smokers in connection with
      estimation of cadmium concentration. The study was conducted in eighty-nine
      health and unexposed occupationally to cadmium inhabitants of Bialystok, smoking
      and non-smoking men and women at age 35-50. The smokers consumed 20 and more
      cigarettes per day for longer period than 10 years. Blood and morning urine were
      collected for analysis. In the urine samples, cadmium concentration (by atomic
      absorption spectrometry) and cotinine concentration (by gas chromatography with
      mass spectrometry), as an indicator of exposure to cigarette smoke, were
      determined. The kidney status was evaluated based on the urinary activities of
      lysosomal enzyme N-acetyl-beta-D-glucosaminidase (NAG) and its isoenzyme B (by
      colourimetrical method modified by Zwierz et al.) and concentrations of
      creatinine and urea in the serum (using diagnostic laboratory tests by POCh). The
      percentage reabsorption of phosphates was evaluated as well (TRP). Cadmium
      concentration in the urine of smoking women and men was higher compared to non
      smokers, but there was no correlation between cadmium and cotinine concentrations
      in urine. In the smoking women, the urinary activity of NAG and TRP were higher
      than in non-smoking ones. In smokers, the activities of NAG and NAG-B in men and
      the activity of NAG-B in women were in the range of values noted in non-smokers,
      however the frequency of appearance of NAG and NAG-B activities above the limit
      of detection was higher compared to non-smokers. Cigarette smoking had no
      influence on the serum concentrations of creatinine and urea in both men and
      women and TRP in men. The results of the analysis of the urinary NAG and NAG-B
      activities in conjunction with the frequency of their appearance allow concluding
      that cigarette smoke might lead to an occurrence of early changes in proximal
      tubules of men and women.

PMID- 15521600
TI  - [Tricholoma equestre--animal toxicity study].
AB  - Animal toxicity study of Tricholoma equestre mushrooms stored for 12 months at (
      )20 degrees C was performed using 30 male BALB/c mice. Three groups of 5 mice
      each were given suspension of T. equestre powder in water, boiled aqueous extract
      and chloroform-methanol extract dissolved in Miglyol 812 by gavage for three
      consecutive days. Mice in control groups were given water, Miglyol 812 and p
      phenylenediamine (CAS 106-50-3). Creatine kinase activity was determined in serum
      collected 72 hours after the final dose. Mean activity of serum creatine kinase
      in mice treated with T. equestre powder, aqueous extract, chloroform-methanol
      extract and Miglyol 812 were 157 +/- 93, 129 +/- 30, 96 +/- 38, 111 +/- 66 U/L
      respectively and did not differ significantly from mean activity in mice which
      were given water (107 +/- 38 U/L). Mean serum creatine kinase activity in p
      phenylenediamine group (265 +/- 63 U/L) was significantly higher than in group
      treated with water (p<0.01). CONCLUSION: Extracts of Tricholoma equestre
      mushrooms stored for 12 months at (-)20 degrees C did not cause rhabdomyolysis in
      male BALB/c mice.

PMID- 15521601
TI  - [Monitoring of tracheal tube cuff pressure in patients treated in intensive
      therapy unit and intensive care units].
AB  - BACKGROUND AND AIM OF THE STUDY: Proper tracheal tube cuff pressure (CP) can
      diminish the risk of side effects. Excessive tracheal tube cuff pressure can
      cause ischaemic changes in the tracheal mucosa, decubitation, granuloma, rupture
      of a trachea, tracheo-oesophageal fistulae or tracheal stenosis. Too low CP is
      also undesirable, because it can increase the leakage of colonized subglottic
      secretions around the tracheal tube cuff, which is the risk factor of ventilatory
      associated pneumonia. Accidental extubation may also occur. The aim of the study
      was to find out if there are any differences in maintenance of the proper CP
      between the staff of intensive therapy unit (ITU) under the supervision of
      anaesthesiologists and staff of intensive care units (ICU) led by non
      anaesthesiologists. MATERIALS AND METHODS: We measured the CP in 219 intubated
      patients. There were 107 patients hospitalized in ITU, under anaesthesiologists's
      surveillance, the other 112 patients in ICUs were supervised by non
      anaesthesiologists. The patients were intubated with Portex Profile Soft-Seal
      Cuff and Mallinckrodt Hi-Lo with low-pressure and high-volume cuffs. The
      manometer PORTEX with the recommended range of CP 16-26 cm H2O (1.56-2.54 kPa).
      The teams were unaware that the audit was taking place. If the CP was out of
      range, it was corrected to the proper values. RESULTS AND CONCLUSIONS: The data
      analysis did not reveal any differences between values of CP in both groups of
      subjects. Over-inflation was more frequent than under-inflation in both groups of
      patients. Regular measurement of tracheal cuff pressure was not a routine
      procedure in the controlled units.

PMID- 15521602
TI  - [C-reactive protein as a useful prognostic marker in acute poisoning].
AB  - All inflammatory processes or damaging factors affecting human organism increase
      the levels of pro-inflammatory proteins, i.e. acute phase proteins, in the serum
      in a statistically significant way. Among these proteins, interleukin-6 and C
      reactive protein (CRP) are of the highest prognostic value for the process
      dynamics. The aim of the present study was to evaluate feasibility of determining
      the level of the CRP as a diagnostic and prognostic marker in acute poisonings.
      Out of a group of 132 patients hospitalised in the Lublin Toxicological Centre,
      67 patients observed were poisoned with the CNS acting agents, 17 patients were
      intoxicated with alcohol, 10 patients overdosed cardio-vascular drugs and 6 were
      exposed to carbon monoxide. In the above mentioned groups, alcohol and CNS acting
      agents increased CRP values in over 33% of the patients, whereas in the case of
      patients under the influence of cardiac drugs or carbon monoxide, the same effect
      was observed in more than 16% of the cases. Moreover, an attempt to evaluate the
      dynamics of the CRP level changes in time was undertaken; a concentration
      increase was observed in 65% of the patients during the second day of
      hospitalisation. Our results suggest that the determination of the C-reactive
      protein levels can be a cheap prognostic test evaluating severity of acute
      poisoning cases.

PMID- 15521603
TI  - [Preparedness of Pomeranian Region hospitals for a possible attack with chemical
      weapons].
AB  - The aim of this study was to find out whether the medical staff in the emergency
      units in all Pomeranian Region hospitals were prepared for possible chemical
      weapon attack. Key medical personnel, senior doctors and nurses, in 24 hospitals
      were interviewed by the authors. None of the medical staff have received training
      in self-protection and management of mass casualties after accidental or
      terroristic chemical release. There were only four hospitals which had adequate
      space and special chambers for decontamination. None of the emergency units had
      special equipment needed for self-protection. The majority of the staff did not
      know their tasks and individual roles in the case of chemical contamination. None
      of the personnel had information about antidotes and place of their storage. Only
      16.7% of the staff knew the source of quick information about specific treatment
      of casualties. CONCLUSIONS: The emergency departments in Pomeranian Region
      hospitals are not prepared for a possible terroristic chemical attack. There is
      an urgent need for training the medical staff in self-protection and management
      of mass casualties after accidental or terroristic chemical release. It is
      important to make bank of antidotes which could be placed in the regional poison
      control centres. All these procedures could be carried out without too much
      expenditure.

PMID- 15521604
TI  - [Diagnostic problems in case of environmental exposure to tetraethyl lead].
AB  - The aim of this study was the presentation of the chronic tetraethyl lead
      poisoning of the 4 person family in the place of settlement. CASE REPORT: 15.5
      years-old man was admitted to the regional Pediatric Ward because of changes of
      behavior, hallucinations, agitation. Nausea, vomiting, metallic taste and
      diarrhea were observed prior to the admission. In the case history, there were no
      data suggested of the toxic origin of the disorder . The CSF examination and CT
      of the brain were normal. Increased activity of CPK, ALT, AST, GTP, LDH in the
      blood were found. Paranoid syndrome was diagnosed by psychiatric evaluation. The
      patients' mother presented similar signs in almost the same time. The laboratory
      tests of the blood taken from the patients' father and older brother revealed the
      increase activity of the same enzymes (CPK, ALT, AST, LDH). All family was
      admitted to the Department of Clinical Toxicology in Krakow because of suspicion
      of the heavy metal poisoning. The toxicological laboratory test showed in all
      described patients the toxic serum lead concentration accordingly: 440 microg/l-
      older brother, 490 microg/l--father, 508 microg/l--mother and 635 microg/l-
      primary described patient. Because of the fact, that were no characteristic for
      lead poisoning changes in blood picture, the toxicological investigations were
      continued. As a result of these examinations presence of a diethyl lead in urine
      was confirmed. In the evaluation of the multiorgan damages connected with
      tetraethyl lead poisoning, we paid special attention on CSN dysfunctions. The USG
      and scintigraphy examinations revealed the liver damage. The different kinds of
      arrhythmias indicated on cardiovascular system damage. Based on clinical
      presentation and laboratory investigations the chronic tetraethyl lead poisoning
      was diagnosed.

PMID- 15521605
TI  - [Late sequelae of tetraethyl lead poisoning].
AB  - In our previous study a tetraethyl lead poisoning due to a rural environmental
      exposure of four family members was described. A differently intensified OUN
      dysfunction dominated clinical picture. Cognition status and degree of OUN
      dysfunction was monitored using generally accepted neurobehavioral test battery.
      The tests applied were fitted individually to each poisoned family member in
      accordance to current intensification of symptoms. Basing on the neurobehavioral
      performance results a consecutive imagine techniques were introduced to full CNS
      evaluation of intoxicated patients. Results of neuropsychological monitoring in
      12 months period were compared to brain CT, SPET 99mTc-ECD used to evaluation of
      regional brain perfusion disturbances, MRI and MRS and presented in the study.

PMID- 15521606
TI  - [Nervous system involvement in three children poisoned with thallium].
AB  - Three children, aged 5, 10 and 16 years, poisoned with thallium were
      hospitalized. Two of them suffered from sensory-motor and third from sensory
      polyneuropathy and additionally in the youngest child severe encephalopathy was
      observed. The correlations between serum and urine thallium levels and the
      severity of the symptoms in the course of the disease were positive. The most
      severe symptoms and the highest thallium level were observed in the youngest
      child.

PMID- 15521607
TI  - [Sudden unilateral sensorineural hearing loss after carbon monoxide
      intoxication].
AB  - A case of unilateral sensorineural hearing loss of the left ear after carbon
      monoxide intoxication was presented. The diagnosis was based upon an interview,
      medical examinations and audiometric investigations. Results of diagnostic
      evaluations, clinical presentation and treatment were discussed. Hearing
      improvement was obtained after 6 days of treatment and normal hearing returned
      after 14 days. Patients who suffer from CO intoxication are at risk of hearing
      impairment, therefore, there is a need for audiometric follow up in these
      patients.

PMID- 15521608
TI  - [Liver albumin dialysis--application in acetaminophen poisoning].
AB  - Acetaminophen is found to be potentially hepatotoxic drug. Both, acute
      acetaminophen intoxication (dose >10 g) and therapeutic dose administration in
      the case of glutathion depletion (chronic alcohol abuse) hepatotoxic effect may
      occur. Late N-acetylcysteine (NAC) administration does not prevent liver injury.
      Molecular Adsorbents Recirculating System (MARS) is useful liver support device
      based on albumin dialysis for saving time for spontaneous liver regeneration or
      bridging technique to liver transplantation. CASE SERIES: Two cases admitted to
      the Department in 19 and 20 hour post-ingestion of hepatotoxic paracetamol doses
      as confirmed by toxiocological examination (serum paracetamol concentration).
      Despite of NAC administration the signs of the liver injury (progressive
      encephalopathy and jaundice, decreased prothrombin activity) developed. On day
      four post exposure according to King's College of Medicine London criteria both
      cases were qualified to MARS therapy. Albumin dialysis of 8 hour duration was
      performed in both cases and a full recovery with normalization of the liver
      function was noted. Patient three: patient with the liver and the kidney
      insufficiency due to alcohol-paracetamol syndrome admitted to the Department of
      Clinical Toxicology for MARS therapy. Five performed dialysis resulted in the
      liver function improvement. The patient was disqualified from the liver
      transplant because of heart failure, pneumonia, hyperthyroidism and alcoholism.
      Patient died because of heart failure.

PMID- 15521609
TI  - [Severe toxic liver failure after acute poisoning with paracetamol, ferrous
      sulphate and naproxen].
AB  - We present the case of 20-year-old woman intoxicated with mixed drugs, composed
      of paracetamol (acetaminophen), ferrous sulphate, naproxen and benzodiazepines.
      Acute toxic liver damage with clinical symptoms of coma resolved at the patient.
      Lack of the past history doesn't let to specific therapy and systemic
      complications. In this data we confirm, that past history, clinical symptoms and
      laboratory results are needed in designing a treatment strategy.

PMID- 15521610
TI  - [Liver transplantation in Amanita phalloides poisoning--authors' experience].
AB  - So far 5 cases of severe acute liver failure in the course of Amanita phalloides
      poisoning, treated in Department of Toxicology in Poznan were regarded for need
      of liver transplantation. In September 2001, 4 patients were directed to
      transplantology center: 3 adult persons were treated in Department of General
      Surgery and Liver Diseases, Medical University of Warsaw, and one 15-year-old boy
      in Department of Pediatric Surgery and Organ Transplantation, Children's Memorial
      Health Institute in Warsaw. According to King's College Hospital criteria a
      family of three qualified for liver transplantation. 40-year-old mother died
      during transplantation, 41-year old father and his 15-year old son underwent
      operation successfully. Two years after liver transplantation these two men were
      admitted to Department of Toxicology in Poznan for their clinical status
      assessment. Based on observations made in Department of Toxicology we conclude
      the management of patients who meet the clinical indicators of poor prognosis
      should be discussed with a transplantology center in the early stage of severe
      acute liver failure.

PMID- 15521611
TI  - [Acute intoxication with baclofen].
AB  - Many authors have noticed an increase in suicidal intoxication with baclofen, a
      lipophilic analog of gamma-aminobutyric acid (GABA). Although morbidity and
      mortality is low in baclofen overdosage however may cause serious respiratory
      failure as also cardiac and neurological system disturbances. The aim of the
      study was to evaluate some clinical aspects of acute intoxication with baclofen.
      We analyzed 18 patients (8 females and 10 males) aged from 15 to 58 (mean 33+/
      15.4) years. Patients were admitted to the Department of Toxicology in the years
      1996-2003 because of suicidal intoxication with baclofen. Number of patients
      intoxicated with baclofen during the last four years of analysis was two times
      more than in the first four years. The doses of baclofen were from 150 to 1500
      (mean 388) mg. There were twelve patients (66%) admitted to the Clinic in deep
      coma (III and IV grade of Matthew scale) with the hyporeflexia and low muscle
      tone. Acute respiratory failure which required mechanical ventilation (6 to 96-
      mean 53.2 hours) was observed in 10 cases (55.5%). Cardiac abnormalities included
      bradycardia (44.4%), hypertension (33.0%) and hypotension (5.5%). Toxic psychoses
      were observed in 6 cases (33.3%). Flumazenil administration had no impact on
      clinical advancement of coma. An increase in creatine kinase activity was
      observed in 12 patients (66.6%). CONCLUSIONS: There was no correlation between
      the dosage of baclofen and the clinical outcome. Baclofen poisoned patients
      should be admitted to hospitals with adequate medical equipment, especially
      respirators.

PMID- 15521612
TI  - [Intoxications with atypical antipsychotic drugs--data of the Acute Intoxication
      Unit in Wroclaw].
AB  - Recently, atypical antipsychotic agents have largely replaced traditional agents
      as first-line drugs for the treatment of schizophrenia and psychotic mood
      disorders. Considering the increase in atypical antipsychotics prescriptions and
      the increased risk of suicide in this patient population, the number of reported
      cases of antipsychotic drugs may be expected to increase. This paper describes
      the clinical course of atypical antipsychotic agents intoxication, chiefly
      clozapine, risperidone and olanzapine. Clozapine was the ingestant in 11 cases of
      atypical antipsychotics overdose in our material. The major observed effects in
      this group included deep coma, tachycardia, hypersalivation, delirium and shock.
      Clozapine has a small therapeutic index; in our patients the mortality rate was
      27%. Ten patients with risperidone overdose were identified. Our data show that
      risperidone toxicity manifests mainly as mild central nervous system effects:
      somnolence, vertigo and tardive dyskinesia. Olanzapine has been considered to be
      similar to clozapine, but olanzapine intoxication appeared to have a relatively
      benign clinical course as compared with clozapine intoxication. In olanzapine
      intoxications deep coma, myosis and mild cardiovascular effects (hypotonia) were
      observed.

PMID- 15521613
TI  - [A group carbon monoxide poisoning].
AB  - The aim of the study was to present the group carbon monoxide poisoning in Krakow
      in December 2003. Despite the reanimation procedure one fatal case was stated on
      the spot (HbCO--60% according to post-mortem toxicological examination). CO
      threshold limit values were significantly exceeded in the whole building. The
      inhabitants (15 persons) were transported to the Department of Clinical
      Toxicology Jagiellonian University Medical College. Also 4 staff members of the
      ambulance and 2 policemen called to the incident, were diagnosed and observed.
      Totally, toxicology medical care was given to 21 CO exposed persons. In 8 of them
      acute CO poisoning of minor grade was stated. Any clinical symptoms of poisoning
      in the rest of CO exposed persons were noted.

PMID- 15521614
TI  - [Symptoms of severe digoxin intoxication in patients hospitalized in geriatric
      wards].
AB  - Digoxin is a drug commonly used in geriatrics. The purpose of the study is to
      present cases of elderly patients hospitalized on the Geriatric Ward of the
      Provincial Neuro-Psychiatric Hospital "Dziekanka" in Gniezno with extremely high
      level of digoxin in the blood serum. The study was based on the case history of
      patients hospitalized on the ward from July 1998 to June 2003. During that time
      83 patients (age: 77.4 +/- 8.1 years old, 60 females and 23 males) were suspected
      to suffer from digoxin intoxication on the basis of their morbid states, and
      their digoxin level in serum was measured. Furthermore, medical documentation of
      four patients with extremely high digoxin level was profoundly analyzed. Such is
      regarded, the level which exceeds by 100% the upper limit of concentration
      believed to be therapeutic (2 ng/ml) which is 4 ng/ml. The paper also includes a
      profile of clinical conditions of the patients at the time of their admission to
      the ward. While analyzing the patients' states, careful attention was drawn to
      the symptoms that might be caused by digoxin intoxication (changes in the ECG,
      central nervous system and gastrointestinal tract disturbances). However, because
      of typical for geriatrics polypathology and not clear characteristic clinical
      symptoms of majority of pathological syndromes, even severe intoxication may turn
      out to be impossible to diagnose. In the paper, coexistence of risk factors
      predisposing to appearance of toxic symptoms such as kidney failure,
      hypoproteinemia, dehydration, hypoxia, electrolyte abnormalities, drug
      interactions, and a possibility of improper taking medication were pointed out.
      It was concluded that lack of specific signs of severe digoxin intoxication among
      the elderly results in the fact that every worsening in a patient's state of
      health of an unknown reason treated with digoxin should be suspected as
      digitalis' glycosides intoxication.

PMID- 15521615
TI  - [Severe pulmonary complications of massive intoxication with calcium channel
      blockers and isosorbide mononitrate--a case report].
AB  - A 22-year-old man was admitted to the acute intoxication unit after suicidal
      intoxication with 100 tablets of verapamil, diltiazem and isosorbide mononitrate.
      He developed shock, paralytic ileus and adult respiratory distress syndrome
      (ARDS). The patient required high doses of catecholamines and mechanical
      ventilation with high inspiratory pressure. Pulmonary barotrauma (pneumothorax,
      pneumomediastinum, pneumoperitoneum and soft tissue emphysema) was a secondary
      complication to mechanical ventilation. It is well known that alveolar epithelial
      type II cells synthesize and secrete all components of the surfactant. Surfactant
      secretion in epithelial type II cells is inhibited by calcium channel blockers
      and it predisposes to develop ARDS. This case illustrates the possibility of ARDS
      in the verapamil and diltiazem intoxication and the need for a heightened
      awareness of this potential complication.

PMID- 15521616
TI  - [Air embolus as a complication of a haemoperfusion catheter removal after
      iatrogenic intoxication with doxorubicin--a case report].
AB  - The case of a 67-year-old patient, treated for melanoma, who was given a toxic
      dose of doxorubicin (600 mg/m2), was described. The haemoperfusion was performed
      a short time after intoxication. No toxic effects were seen during the
      observation for three weeks. The catheter was removed from the sitting patient by
      an oncologist. The patient abruptly lost consciousness, there were also cyanosis,
      loss of muscle tone and apnea. The reanimation was unsuccessful. The air embolism
      was probably the cause of death. The diagnosis was confirmed by the sudden
      attack, wide duct after the removal of catheter, sitting position of the patient
      and the presence of foramen ovale found during autopsy. CONCLUSIONS: Cannulation
      as well as decannulation of the central vessels should be performed by
      experienced doctors. Decannulation should always be done in the Trendelenburg
      position.

PMID- 15521617
TI  - [Clinical and toxicological evaluation of fatal poisoning with amphetamine
      derivative--MDMA, ecstasy (3,4-methylenedioxymethamphetamine)].
AB  - Intoxications with amphetamine derivatives represent an important problem of
      clinical and forensic toxicology. Even if distribution of the drug group has been
      legally forbidden, they continue to pose serious threats, linked to their
      uncontrolled administration which frequently leads to lethal intoxications. We
      present a case of intoxication in a 17-year-old male with amphetamine derivate-
      MDMA, Ecstasy. Clinical analysis documented an acute multi-organ failure, in
      particular pronounced hepatic and renal insufficiency, disseminated intravascular
      clotting (DIC). The comprehensive diagnosis and resulting discharge abstract of
      the acute poisoning were confirmed by postmortem investigations.

PMID- 15521618
TI  - [Hair analysis as a document of oxcarbazepine therapy in fatal levomepromazine
      poisoning].
AB  - A development of contemporary analytical methods makes possible to use hairs in
      toxicological analysis for documentation history of drug administration. An
      undertaken subject has been illustrated by a suicidal fatal poisoning of 58-year
      old man with a neuroleptic drug--levomepromazine. Toxicological analysis carried
      out by HPLC/APCI/MS, besides of standardized postmortem specimen as blood, urine,
      liver and cerebrospinal fluid included also victim hairs. As a result of
      analytical procedure levomepromazine at high concentrations was revealed, which
      may be responsible for death. Moreover, and antiepileptic drug--oxcarbazepine and
      two main metabolites at therapeutic concentrations were revealed parallel. In
      three 2-cm segments of hair oxcarbazepine and two metabolites were detected,
      levomepromazine, in contrary, was not detected in this specimen. Complex chemical
      toxicological investigation confirmed information that victim was an epileptic
      patient and was treated with oxcarbazepine at least 6 months before death while
      toxic dose of levomepromazine, as one could suppose, he took to commit suicide.

PMID- 15521619
TI  - [Acute poisoning with lithium carbonate in a young woman--case report].
AB  - In the clinical practice there are three types of lithium intoxication: acute
      poisoning in patients not previously treated with lithium, acute on chronic
      poisoning, i.e., an acute overdose in patients who are under lithium treatment
      and chronic poisoning that occurs in patients who are under lithium treatment.
      Threats and the clinical management in these types are different. The paper
      describes a case of a young woman acutely intoxicated with lithium carbonate,
      never treated lithium before. Plasma concentration of lithium, 15 hours after
      ingestion of 9.75 g lithium carbonate, was 2.56 mmol/L. Only minor clinical
      symptoms were observed. Calculated elimination half-life was 15-26.8 hours.

PMID- 15521620
TI  - [Envenoming by Malayan cobra (Naja naja sputatrix)--case report].
AB  - Malayan cobra (Naja naja sputatrix) is the venomous snake of the Elapidae family
      which involves at least three species of Asian spitting cobras, according to the
      new taxonomy. This snake occurs naturally in southeastern Asia and in Poland it
      is kept only in the private breedings. Its venom mainly contains neurotoxins
      which have paralyzing activities to the nervous system and cardiotoxins which act
      cytolytically. The present study shows a case of the forty-one-year-old man
      professionally engaging in venomous reptiles who was bitten in his left ring
      finger by the Malayan cobra. No general symptoms, especially neurotoxic, were
      observed in the patient after the snake bite, but there was a significant local
      tissue injury including necrosis. In the bite site the infection with Morganella
      morganii developed with consequent phlegmon within the hand and the forearm.
      Additionally, features of haemolysis and injury of muscles with elevated level of
      serum creatine phosphokinase (CPK) were present. The local injuries of tissues
      were treated surgically including the amputation of the bitten finger which has
      undergone the necrosis. No specific antivenom was used in the treatment.

PMID- 15521621
TI  - [Envenoming by common viper (Vipera berus)--subject still exists...].
AB  - The only venomous reptile that naturally occurs in Poland is the adder or common
      viper (Vipera berus). Its bites are not of great epidemiological importance, but
      in some cases serious life-threatening symptoms may appear. The most common
      symptoms of adder envenomation are: local edema, reddening and pain of the bitten
      site and also the general symptoms coming from the alimentary tract (vomiting,
      diarrhoea, abdominal pain), the circulatory system (hypotension, shock, ECG
      abnormalities), the central nervous system (sleepiness, vertigo, disorientation,
      loss of consciousness), hematological symptoms (leukocytosis, hemolysis,
      coagulopathy) and allergic symptoms (fever, urticaria, angio-oedema). In the
      present study we described the case of a twenty-year-old patient hospitalized at
      the Toxicology Department of the Collegium Medicum UJ after a viper bite. Except
      for some above-mentioned symptoms he also developed ocular symptoms like ptosis
      and blurred vision. Such symptoms after the common viper bite have not been
      described in the literature till now. The cause of them seems to be an intense
      allergic reaction in the region of the orbit and eyelids all the more so because
      the patient had the positive allergy history. However, taking into account the
      latest reports from the literature, a neurotoxic action of some components of the
      Vipera berus venom may also play a role. Because of the developing general
      symptoms a specific equine antivenom was administered to the patient, apart from
      the supportive care, without any serious side effects that usually are observed
      after the use of such a kind of sera. It is thought that the sheep antivenom is
      better than the equine one considering a lack of allergic side effects. As a
      result of applied treatment the local and general symptoms including ocular
      symptoms subsided.

PMID- 15521622
TI  - [Fatal suicidal intoxication with cetirizine in patient with anorexia--a case
      report].
AB  - According to the best of our knowledge this is the first case of acute fatal
      intoxication with cetirizine published in medical literature. We have described
      the case of a 18-year-old female with the history of anorexia for 2 years, who
      was admitted to Clinic of Toxicology because of suicidal attempt with use of
      cetirizine. The laboratory results revealed metabolic acidosis with the pH 7.13;
      pO2 88 mm Hg; pCO2 36 mm Hg; HCO3 12.0 mmol/L; BE (-)17 mmol/L; SO2 100% and
      hypokalemia (K+ 3.1 mmol/L). On physical examination blood pressure was 70/40 mm
      Hg, heart rate was 36-40 beats/min. Convulsions were observed. After about two
      hours of intensive treatment there was a cardiac arrest in the form of
      ventricular fibrillation. The resuscitation procedures which lasted for over 2.5
      hours were ineffective. The high dose (270 mg) of cetirizine as well as anorexia
      and hypokalemia could have been the cause of the unique character of the symptoms
      in this case. Further investigations should be carried out to confirm the safety
      of cetirizine in the conditions of massive intoxication and with coexistence of
      other risk factors.

PMID- 15521623
TI  - [Acute intoxication with fenspiride].
AB  - According to the best of our knowledge this is the first publication in medical
      literature about the acute intoxication with fenspiride. The two cases of a young
      female patients, intoxicated with Eurespal, were described. The orthostatic
      hypotonia with the blood pressure about 105-115/70 mm Hg in the horizontal
      position and 70-80/40 mm Hg in the sitting position was dominating. The heart
      rate was 100-110/min. when lying and 130-140/min. when sitting. The main symptoms
      were probably caused by inhibition of alpha1 adrenergic receptors. CONCLUSION:
      Main clinical manifestations make us reconsider the opinion about safety of
      fenspiride especially after acute intoxication.

PMID- 15521624
TI  - [Acute oral suicidal intoxication with captan--a case report].
AB  - According to the best of our knowledge the second case of acute intoxication with
      captan was described. In this paper a 22-year old female was admitted to the
      Department of Toxicology with a nausea, weakness, numbness of upper limbs and
      substernal pain. She said that these symptoms began two hours after suicidal
      ingestion of 5.0 g of captan. At admission the patient was alert. Temperature was
      37 degrees C, heart rate 100-120 b/min., BP 100-120/60-70 mm Hg and breathing
      rate 17/min. WBC were slightly elevated 12.4 x 10(3)/microl as well as the
      creatine kinase activity 329 U/L. ECG showed inversion of a T segment in V1-V4
      leads. ECHO-sound made in 4th and 120th day after the onset of intoxication
      showed no changes, with EF--70%. Temporary increase of creatine kinase activity
      as well as the presence of inverted T segment in V1-V4 leads may suggest
      cardiotoxic effects of captan during acute intoxication.

PMID- 15521625
TI  - [Rules of telephone poison information service: guidelines for call management].
AB  - A rules of telephone poison information service for general public and telephone
      toxicological consultation for medical staff, mainly physicians, are presented in
      the study. Guidelines for call management: necessity of caller assessment while
      dealing with information given to the general public and factors that influence
      successful telephone encounters are presented. The types of questions that are
      appropriate to ask about patient, considering both the patient state and the
      toxin(s) involved while dealing with a telephone toxicological consultation are
      also presented.

PMID- 15521626
TI  - [Proper use of own data bases warranted by call recording system].
AB  - A newly created computer system for call (toxicological information) recording
      and a Base of Toxic Substances created in native Polish language are presented in
      the paper. An extended structure of this data base enable to catalogue different
      groups of toxic substances (e.g. medication drugs, psychoactive substances,
      pesticides), and toxins (animals' poisons, toxic plants and mushrooms) concerning
      their specificity. Construction of the Base also enable to reach necessary
      information quickly. What more, identification of toxic substances could be
      easier due to possibility enclosing photos.

PMID- 15521627
TI  - [Animal model of addiction].
AB  - Animal models are a valuable tool in the investigation of the nervous system.
      Many similarities between animal and human dependency behaviours have been
      observed. Animal model based on the self-administration response has contributed
      to understanding of the neurobiological basis of particular stages of the
      dependence process. Animals are used also to study the mechanism of alcohol
      dependence. Working out an animals model of addiction should include references
      to the clinically important phenomena related to psychological dependence which
      has not been displayed. This situation get us to consider the latest findings and
      theories about evolution of the wise human.

PMID- 15521628
TI  - Leishmania donovani is the only cause of visceral leishmaniasis in East Africa;
      previous descriptions of L. infantum and "L. archibaldi" from this region are a
      consequence of convergent evolution in the isoenzyme data.
AB  - Isoenzyme-based studies have identified 3 taxa/species/'phylogenetic complexes'
      as agents of visceral leishmaniasis in Sudan: L. donovani, L. infantum and "L.
      archibaldi". However, these observations remain controversial. A new chitinase
      gene phylogeny was constructed in which stocks of all 3 putative species isolated
      in Sudan formed a monophyletic clade. In order to construct a more robust
      classification of the L. donovani complex, a panel of 16 microsatellite markers
      was used to describe 39 stocks of these 3 species. All "L. donovani complex"
      stocks from Sudan were again found to form a single monophyletic clade. L.
      donovani ss stocks from India and Kenya were found to form 2 region-specific
      clades. The partial sequence of the glutamate oxaloacetate transaminase (GOT)
      gene of 17 L. donovani complex stocks was obtained. A single nucleotide
      polymorphism in the GOT gene appeared to underlie the isoenzyme classification.
      It was concluded that isoenzyme-based identification is unsafe for stocks
      isolated in L. donovani endemic areas and identified as L. infantum. It was also
      concluded that the name L. archibaldi is invalid and that only a single
      visceralizing species, Leishmania donovani, is found in East Africa.

PMID- 15521629
TI  - The molecular diagnosis of Marteilia refringens and differentiation between
      Marteilia strains infecting oysters and mussels based on the rDNA IGS sequence.
AB  - Marteilia refringens is a paramyxean parasite which infects the flat oyster
      Ostrea edulis and mussels (Mytilus galloprovincialis), where it has been
      attributed to a separate species, Marteilia maurini, by several authors. Doubts
      persist though as to the existence or not of two species of Marteilia in Europe.
      We have devised a molecular method for the diagnosis of M. refringens based on
      358 bp nested-PCR of the rDNA intergene spacer (rDNA IGS) which is capable of
      detecting 0.5 fg of M. refringens DNA. Molecular characterization of this spacer
      indicates that the Marteilia parasites which infect oysters and mussels are two
      different strains of the same species.

PMID- 15521630
TI  - The alteration in signal transduction parameters induced by the excretory
      secretory product from Giardia lamblia.
AB  - The mechanism by which Giardia lamblia exerts its pathogenicity is likely to be
      multifactorial. A 58 kDa enterotoxin was purified and characterized from the
      excretory-secretory product (ESP) of the parasite (Kaur et al. 2001). In the
      present study an attempt has been made to elucidate the mechanism of action of
      the ESP, a potentially important enterotoxin. A 41 kDa glycoprotein was
      identified in the mouse enterocyte membrane fraction with which the ESP
      interacted in a GM1-specific manner. The GTPase activity was reduced in
      enterocytes stimulated with the ESP, resulting in an increase in the level of
      adenylate cyclase-dependent cyclic adenosine monophosphate (cAMP). The activity
      of protein kinase A (PKA) in the enterocytes was also upregulated after ESP
      treatment. Ultimately, a significant increase in intracellular Ca2+ concentration
      and decrease in cytosolic Cl- level were noticed in ESP-stimulated mouse
      enterocytes. Thus it is possible that the enterotoxic ESP could bind to the 41
      kDa glycoprotein (receptor?) on the enterocytes and activate the G-protein
      mediated signal transduction pathway resulting in alteration of electrolyte
      transport.

PMID- 15521631
TI  - Reservosome: an endocytic compartment in epimastigote forms of the protozoan
      Trypanosoma cruzi (Kinetoplastida: Trypanosomatidae). Correlation between
      endocytosis of nutrients and cell differentiation.
AB  - Reservosomes are large membrane-bound organelles found at the posterior end of
      epimastigote forms of Trypanosoma cruzi, but absent in amastigotes and
      trypomastigotes. We have transferred bloodstream trypomastigotes to LIT medium
      supplemented with gold-labelled transferrin in order to analyse, at the
      ultrastructural level, the occurrence of reservosomes and endocytosis during the
      trypomastigote to epimastigote differentiation. After 24 h, the trypomastigotes
      differentiated into amastigotes, which adhered to each other forming large
      clusters. Electron-dense vesicles were detected close to the Golgi complex in
      cells with intermediary characteristics between amastigotes and epimastigotes,
      but typical reservosomes at the posterior cell tip were still absent. Transferrin
      gold complexes were observed only bound to the surface of clustered cells. After
      72 h, epimastigotes were observed being released from the clusters and free
      swimming epimastigotes appeared, containing electron-dense vesicles at their
      posterior region. Typical reservosomes, labelled with transferrin-gold, were
      observed only in free-swimming epimastigotes. When fully differentiated
      epimastigotes were incubated with transferrin-gold complexes and then processed
      for the immunocytochemical detection of cysteine proteinase, all reservosomes
      were positive for the enzyme, but co-localization of both markers did not occur
      in all organelles. Our data demonstrate that in T. cruzi epimastigotes
      endocytosis is strongly related to reservosome biogenesis during the
      trypomastigote to epimastigote differentiation process.

PMID- 15521632
TI  - Comparison of four serological tests for the diagnosis of Chagas disease in a
      Colombian endemic area.
AB  - The performance of 4 serological tests for the diagnosis of Chagas disease was
      evaluated in Santander, Colombia, a region still presenting active transmission.
      Serum samples from 638 individuals were submitted to an enzyme immunoassay test
      (EIA), using total lysate of a local Trypanosoma cruzi strain and 52.5% were
      positive (335/638). A subset of this group (94 positive individuals and 90
      seronegatives) was randomly selected for further serological confirmation. Three
      additional tests were used--indirect immunofluorescence (IIF) and 2 distinct
      enzyme-linked immunosorbent assays using total lysate of the Y strain (EIA BM)
      and a mixture of 2 recombinant antigens (EIA RA). Seventy-nine patients were
      seropositive in all tests (84.0%-79/94). The number of positive sera with the
      IIF, EIA RA and EIA BM was 84/94 (89.4%), 80/94 (85.1%) and 79/94 (84.0%),
      respectively. In 15 out of the 94 EIA seropositive patients (16.0%), 10
      individuals were negative in all 3 tests (10.6%-10/94). One was negative in the
      EIA BM and positive in the other two tests (1.1%-1/94) and 4 patients were
      positive, solely, in the IIF assay (4.3%-4/94). Relative to the 90 EIA negative
      individuals, 89 were confirmed in all other tests (98.9%-89/90). One individual,
      although seronegative in the IIF, was positive in both confirmatory EIA tests
      (1.1%-1/90). In addition, 120 blood specimens were submitted to PCR
      amplification. This group consisted of 79 confirmed seropositive cases, 16
      individuals with discordant serological results and 25 validated seronegative
      individuals. The PCR was able to detect the presence of parasite DNA in 67 out of
      the 79 seropositive patients (84.8%), in 8 individuals with discordant serology
      (50.0%) and in only one seronegative individual (4.0%). The results pointed to
      the necessity for performing more than one serological test, preferentially with
      antigens from autochthonous strains, to achieve a reliable diagnosis of Chagas
      disease in Colombia.

PMID- 15521633
TI  - Human infectivity trait in Trypanosoma brucei: stability, heritability and
      relationship to sra expression.
AB  - Some Trypanosoma brucei lines infect humans whereas others do not because the
      parasites are lysed by human serum. We have developed a robust, quantitative in
      vitro assay based on differential uptake of fluorescent dyes by live and dead
      trypanosomes to quantify the extent and kinetics of killing by human serum. This
      method has been used to discriminate between 3 classes of human serum resistance;
      sensitive, resistant and intermediate. TREU 927/4, the parasite used for the T.
      brucei genome project, is intermediate. The phenotype is expressed in both
      bloodstream and metacyclic forms, is stably expressed during chronic infections
      and on cyclical transmission through tsetse flies. Trypanosomes of intermediate
      phenotype are distinguished from sensitive populations of cells by the slower
      rate of lysis and by the potential to become fully resistant to killing by human
      serum as a result of selection or long-term serial passaging in mice, and to pass
      on full resistance phenotype to its progeny in a genetic cross. The sra gene has
      been shown previously to determine human serum resistance in T. brucei but
      screening for the presence and expression of this gene indicated that it is not
      responsible for the human serum resistance phenotype in the trypanosome lines
      that we have examined, indicating that an alternative mechanism for HSR exists in
      these stocks. Examination of the inheritance of the phenotype in F1 hybrids for
      both bloodstream and metacyclic stages from 2 genetic crosses demonstrated that
      the phenotype is co-inherited in both life-cycle stages in a manner consistent
      with being a Mendelian trait, determined by only one or a few genes.

PMID- 15521634
TI  - Increased cell proliferation of mouse fibroblast NIH-3T3 in vitro induced by
      excretory/secretory product(s) from Opisthorchis viverrini.
AB  - Infection by Opisthorchis viverrini is a strong risk factor for
      cholangiocarcinoma. However, the mechanism by which the parasite is involved in
      carcinogenesis is not clear. In addition to the direct damage of the bile duct
      epithelium via direct contact with O. viverrini, the excretory/secretory (ES)
      product(s) released from the parasites may play important roles in this process.
      We therefore investigated the responses of a fibroblast cell line, NIH-3T3, to ES
      product(s) released from O. viverrini by using a non-contact co-culture
      technique. In this culture system, the parasites in the upper chamber had no
      direct contact with the NIH-3T3 cells in the lower chamber of the culture plate.
      The results indicated a marked increase in NIH-3T3 cell proliferation in the non
      contact co-culture condition with either 0% or 10% calf serum in the medium
      compared with that without parasites. ES product(s) increased cell proliferation
      by stimulating the expression of phosphorylated retinoblastoma (pRB) and cyclin
      D1, the key proteins in driving cells through the G1/S transition point of the
      cell cycle. This led to the induction of cells going into the S-phase of the cell
      cycle. ES product(s) also changed the morphology of NIH-3T3 cells to a refractive
      and narrow shape, which allowed the cells to proliferate in the limited culture
      area. For the first time, we have been able to demonstrate increased cell
      proliferation induced by the ES product(s) from O. viverrini; this finding may
      clarify how O. viverrini ES product(s) affect human bile duct epithelium during
      cholangiocarcinogenesis.

PMID- 15521636
TI  - Eye fluke-induced cataract formation in fish: quantitative analysis using an
      ophthalmological microscope.
AB  - We examined the parasite-induced cataract formation in rainbow trout
      (Oncorhynchus mykiss) using slit-lamp microscopy to determine the relationship
      between cataract intensity and number of Diplostomum spathaceum parasites that
      were established in the lens. Cataract intensity increased significantly with
      parasite burden, but was also affected by the pattern of exposure to the parasite
      cercariae. The slit-lamp methodology proved useful in scoring the cataracts since
      it provides a 3-dimensional view into the lens and gives an actual picture of the
      location and intensity of the cataracts, which allows detailed investigations of
      mechanisms underlying cataract formation in various fish species. Potential
      applications of the method in fish farming and parasitological studies are
      discussed.

PMID- 15521635
TI  - Glycosidase activity in the excretory-secretory products of the liver fluke,
      Fasciola hepatica.
AB  - Fasciola hepatica secretes proteolytic enzymes and other molecules that are
      essential for host penetration and migration. This mixture may include enzymes
      required for the degradation of supramucosal gels, which defend epithelial
      surfaces against pathogen entry. These contain hydrated mucins that are heavily
      glycosylated. Excretory-secretory products (ES) from F. hepatica were examined
      for a range of glycosidase activities, using synthetic 4-methylumbelliferyl
      glycosides as substrates. The ES product contained at least 8 different
      glycosidase activities, the most abundant of which were beta-N
      acetylhexosaminidase, beta-galactosidase and beta-glucosidase. Alpha-fucosidase,
      beta-glucuronidase, alpha-galactosidase, alpha-mannosidase and neuraminidase were
      also present. Beta-N-acetylhexosaminidase and beta-galactosidase were present in
      multiple isoforms (at least 4), whereas beta-glucosidase appeared to exist as one
      isoenzyme with a pI < 3.8. All three enzymes had acidic pH optima (4.5-5.0).
      Ovine small intestinal mucin was degraded by ES at pH 4.5 or 7.0, with or without
      active cathepsin L, the major protease found in F. hepatica ES. The ability of F.
      hepatica ES to degrade mucin in the presence or absence of active cathepsin L
      suggests that cathepsin L is not essential for mucin degradation. The abundance
      of beta-galactosidase and beta-hexosaminidase in ES supports a role for these
      enzymes in mucin degradation.

PMID- 15521637
TI  - Characterization of major sperm protein genes and their expression in
      Oesophagostomum dentatum (Nematoda: Strongylida).
AB  - Major sperm protein (msp) genes were isolated from complementary (cDNA) and
      genomic DNA libraries prepared from the parasitic nematode, Oesophagostomum
      dentatum, characterized at the nucleotide and amino acid (aa) levels, and their
      expression was investigated. Three different msp cDNA and 2 genomic sequences
      were determined, each with an open reading frame (ORF) of 381 nucleotides.
      Nucleotide variation was detected at 30 positions in the ORF among all 5
      sequences. Conceptual translation of the full-length msp sequences inferred 4
      different MSPs each of 126 aa. These predicted MSPs differed at aa positions 15
      (serine <----> threonine), 101 (alanine <----> glycine), 103 (glutamine <---->
      leucine) and 126 (proline <----> leucine). Southern blot analysis of O. dentatum
      genomic DNA, digested separately with various restriction endonucleases,
      displayed multiple (n = 7-13) bands for each enzyme, providing support for a
      multigene family. Also, at the genomic level, sequence tracts consistent with a
      'substitute' TATA box sequence motif were identified within a region (-1 to -123
      nt) preceding the 2 msp genes. In contrast to other species of nematode
      investigated to date, no GATA transcription factor binding motif was detected
      immediately upstream of the msp coding region. Real-time PCR analysis
      demonstrated that msp mRNA was expressed exclusively in the males of both fourth
      stage larvae (L4s) and adults of O. dentatum (raised in pigs after intragastric
      inoculation). The magnitude of expression in male O. dentatum raised in pigs in
      the presence of female worms was the same as in males in the absence of females.
      Comparative analyses showed aa sequence conservation among MSPs from various
      nematodes, suggesting similar functional roles for these proteins.

PMID- 15521638
TI  - Differences in susceptibility of the European eel (Anguilla anguilla) and the
      Japanese eel (Anguilla japonica) to the swim-bladder nematode Anguillicola
      crassus.
AB  - The swim-bladder nematode Anguillicola crassus originates from the Far East where
      it is a parasite of the Japanese eel (Anguilla japonica). After A. crassus was
      introduced to Europe, it became a predominant parasite of the European eel
      (Anguilla anguilla). A study performed with experimentally infected eels (98
      days, 23 degrees C) revealed significant differences in the susceptibility of the
      two eel species to this parasite. The recovery rate of 30 administered infective
      A. crassus larvae (L3) from A. japonica was less than half of that from A.
      anguilla (33.2% and 13.8%, respectively). Almost 60% of the worms recovered from
      A. japonica were found as dead, encapsulated and necrotic larvae in the
      swimbladder wall. In contrast, no dead larvae were found in A. anguilla.
      Additionally, the development of the worms was shown to be significantly slower
      in A. japonica compared with A. anguilla. The lower survival rate of the worms,
      together with their slower development, resulted in a significantly lower adult
      worm burden (11 and 428 mg wet weight, respectively) and in a decreased
      reproductive success in A. japonica compared with A. anguilla. These results
      demonstrate that the original host, A. japonica, possesses more effective defence
      mechanisms against A. crassus than does the non-adapted host, A. anguilla.

PMID- 15521639
TI  - Effect of cyclosporin A on the survival and ultrastructure of Echinococcus
      granulosus protoscoleces in vitro.
AB  - Surgical treatment of human hydatidsosis involves the use of various scolicidal
      agents to kill infective Echinococcus granulosus protoscoleces that may
      disseminate into the peritoneal cavity during surgery and potentially re-infect
      the patient. Currently, no scolicidal agent is completely effective in killing
      intracystic protoscoleces in humans. Cyclosporin A (CsA) has previously been
      found to be lethal for E. granulosus protoscoleces in vitro. In this study, we
      further assessed the effectiveness of CsA as a scolicidal agent by testing the
      toxic effect of CsA at higher doses over various time-periods. Experiments were
      performed on activated and unactivated protoscoleces cultured in nutrient medium
      or sheep hydatid cyst fluid. All activated protoscoleces were killed following
      culture in 100 microg/ml of CsA for 3 days and 50 or 20 microg/ml for 5 days. The
      lethal effect of CsA on unactivated protoscoleces varied but reached 100% over 15
      days in culture with 100 or 50 microg/ml of CsA. Pulse treatment of protoscoleces
      with 50, 20 or 10 microg/ml of CsA for 5 min or 72 h killed all parasites by day
      10 and day 5 respectively. Untreated protoscoleces remained greater than 95 %
      viable for the duration of experiments. Changes in protoscolex ultrastructure
      induced by treatment with 10 microg/ml of CsA over 10 days in in vitro culture
      was assessed by TEM. Protoscolex alterations observed in treated parasites
      included an increase in cellular vacuolization, swelling of mitochondria,
      rounding of cells, damage to the tegument, decrease in glycogen, a breakdown of
      the extracellular matrix and an increase in lipid globules. The untreated
      protoscoleces, by comparison, had few changes during the 10-day culture period
      with the exception of large amounts of extracellular glycogen observed in the
      protoscoleces at culture days 7 and 10. From these results, CsA is clearly an
      effective scolicidal agent in vitro that may have potential application as a new
      therapeutic agent in the treatment of human hydatid disease.

PMID- 15521640
TI  - Is sex-biased ectoparasitism related to sexual size dimorphism in small mammals
      of Central Europe?
AB  - Sexual size dimorphism (SSD) in mammals reveals the extent of sexual selection,
      which may in turn explain why males are often more infected by parasites than
      females and that parasites may contribute to the association between SSD and male
      biased mortality. Here, we investigated the relationship between SSD in small
      mammals of Central Europe and the differences in sex infection by fleas. A
      comparative analysis was conducted for 10 species of rodents and insectivores. We
      found that males harbour higher flea species richness than females and that the
      abundance of fleas is higher in males than in females. This difference is not
      related to male-biased density. However, contrary to our hypothesis, we found
      that an increase in SSD is not related to an increase in male infection by fleas
      compared with female infection. We discuss our results in term of sex-differences
      in immunocompetence and/or sex-differences in behaviour.

PMID- 15521641
TI  - Onto-phylogenetic aspect of myotomal myogenesis in Chordata.
AB  - This paper presents an onto- and phylogenetic aspect of myotoamal myogenesis in
      Chordata. A comparative analysis of early stages of myotomal myogenesis in
      Chordata indicates that the myogenic process in this phylum underwent
      evolutionary changes. The first stage of the process is myogenesis leading to
      development of mononucleate mature muscle cells, the most advanced stage is
      formation of multinucleate muscle fibres.

PMID- 15521642
TI  - Effects of Thaumetopoea pityocampa (Lepidoptera: Thaumetopoeidae) larvae on the
      degranulation of dermal mast cells in mice; an electron microscopic study.
AB  - The pine caterpillar Thaumetopoea pityocampa (Lepidoptera: Thaumetopoeidae) is
      found in pine woods. Hairs of the T. pityocampa caterpillar cause a cutaneous
      reaction in humans and animals. Mast cells are responsible for allergic reactions
      in mammals. In this study male swiss albino mice were divided into two groups: 5
      mice in the control group and 25 mice in the experimental group. The dorsal skin
      of mice was shaved. The mice in the experimental group and T. pityocampa larvae
      (fifth instar, approximately n=100) were put in the same cage. Dermal mast cells
      of mice exposed to T. pityocampa were examined with a transmission electron
      microscope and compared to the control group 1, 3, 6, 12 and 24 hours after
      exposure. Dermal mast cell degranulation in mice was observed 12 and 24 hours
      after exposure.

PMID- 15521643
TI  - Spreading-independent growth of normal fibroblasts in three-dimensional cultures.
AB  - Changes of cell shape resulting from cellular flattening on culture substratum
      have previously been demonstrated to correlate with mitotic activity of normal
      animal cells in monolayer cultures. Here, we compared the shapes and
      proliferation of chick embryo fibroblasts cultured either in multicellular,
      multilayered sheets extended between glass fibres, or in standard monolayers.
      Fibroblasts in sheets retained the mitotic activity characteristic of that
      observed in sparse monolayer cultures, i.e. considerably higher that in confluent
      monolayers. Morphometric analyses revealed, however, that the cells in sheets
      were considerably less flattened than in monolayer cultures. These observations
      indicate that the modulation of culture conditions resulting in multidirectional
      cell stretching leads to the dissociation of flattening and mitotic activity of
      normal animal cells, so long as an intracellular stress field, generated by
      contractile cytoskeleton and stabilised by intercellular contacts, is maintained.

PMID- 15521644
TI  - C-banding karyotype and relationship of the dipodids Allactaga and Jaculus
      (Mammalia: Rodentia) in Egypt.
AB  - The C-banding karyotype of the jerboas Allactaga tetradactyla, Jaculus jaculus
      jaculus, and Jaculus orientalis was described and interspecific relationships
      were discussed. Despite the conservation of a relatively small amount of C
      heterochromatin located at the centromeric region of some chromosomes in all
      karyotypes, a striking loss of C-heterochromatin was clearly observed in J.
      orientalis. C-bands were totally absent in 33 of the 48 chromosomes of J.
      orientalis, compared to only 7 for J.j.jaculus and 11 for A. tetradactyla. The
      differences in C-banding amongst karyotypes of the three species were attributed
      either to transformation of heterochromatin into euchromatin or vice versa,
      deletion of heterochromatic segments resulting from pericentric inversions, or to
      variation of euchromatin content and its correlation with the chromosome size and
      arrangement of heterochromatin. The present findings are consistent with the main
      hypotheses derived from morphological, chromosomal, and biochemical data that the
      genera Allactaga and Jaculus have independently developed from a common ancestral
      form and that J. jaculus and J. orientalis are both distinct congeneric species,
      but revealed that the C-banding karyotypes of both J.j.jaculus and J. orientalis
      are distantly related to each other. Therefore, it is concluded that the
      karyotype of J.j.jaculus may be ancestral and that of J. orientalis may have
      derived from it.